PMID- 16274581
TI  - Pelvic examination for detecting ovarian cancer.

PMID- 16274583
TI  - Sex and the cervix: hormones, infections and cancers.

PMID- 16274584
TI  - Sex, medicine and the Tudors.

PMID- 16274585
TI  - Senior house officer in sexual health.

PMID- 16274586
TI  - Health informatics professionalism in primary care.

PMID- 16274587
TI  - A survey of computer use in Scottish primary care: general practitioners are no
      longer technophobic but other primary care staff need better computer access.
AB  - OBJECTIVE: To describe the use of computing systems by primary care staff in
      Scotland. Participants Practice managers in Scotland on behalf of their practice
      teams. METHODS: A survey of computer use in Scottish general practices was
      carried out by the Scottish Clinical Information Management in Primary Care
      (SCIMP) group in April 2001. Every practice was sent an electronic copy of a
      questionnaire using NHSnet. Practices that did not respond to the electronic
      version were sent a paper version of the questionnaire. MAIN OUTCOME MEASURES:
      Access to computers, use during consultations, links to laboratories, problems
      experienced by users. RESULTS: A total of 308 practices (30%) replied to the
      electronic questionnaire and 346 practices (33%) to a paper version, giving an
      overall response rate of 63% (654 practices). A total of 296 (29%) of practices
      could not receive the electronic version. It was reported that 94% of general
      practitioners and 74% of practice nurses frequently used a computer; 72% of
      practices used their computer for chronic disease management. There was great
      variability in links to laboratories for lab results (range 1-30% by region). Of
      responding practices, 16% had plans for a unified patient record, but access to a
      computer is still a major problem for community nurses. Satisfaction was
      expressed for all systems and many practices also use third-party programs.
      CONCLUSIONS: Most Scottish doctors make frequent use of computers for a variety
      of clinical and practice management activities. Many other staff want to make
      greater use of computers, but are often unable to obtain access.

PMID- 16274588
TI  - An intelligent partner system for improving chronic illness care.
AB  - Chronic care consists of a sequence of actions to treat a specific clinical
      disorder over time as a function of the ways in which illness progresses and
      patients respond to management actions. Outcomes depend on physicians' skills to
      select the actions best suited for their patients and competent self-management.
      This paper presents the architecture of an intelligent partner system (IPS),
      which helps to provide doctors with relevant data and skills and empowers
      chronically ill patients with the information and confidence to manage their
      health wisely. The services of this intelligent system are presented as
      'therapies' for the information-processing 'pathologies' associated with
      traditional chronic illness care.

PMID- 16274589
TI  - What does information about referrals reveal about the service network?
AB  - OBJECTIVE: To identify the most important referring parties in the Finnish health
      care system. DESIGN: A record linkage study based on nationwide administrative
      registers. SETTING: The hospital discharge register during 1996 to 2000.
      SUBJECTS: The total Finnish population and the population of four hospital
      districts. MAIN OUTCOME MEASURES: Discharges of individuals by the most important
      referring parties. RESULTS: The five most important referring parties in order of
      magnitude are as follows: health centre, no referral, clinic/unit of the same
      hospital, hospital other than a health centre, and private health care. The five
      most important referring parties for those aged over 75 are the same mentioned
      above. There were regional differences in referral practices. CONCLUSIONS:
      Differences or changes in referral profiles as a function of time cannot be taken
      as a direct measure of the impact of possible interventions or as an indication
      of an actual difference between the areas compared. One should also always be
      aware about any related meta-knowledge.

PMID- 16274590
TI  - Using email as a research tool in general practice: starting to implement the
      National Service Framework for Mental Health.
AB  - INTRODUCTION: The first primary care trust milestone for implementation of
      Standard 2 of the National Service Framework for Mental Health is the use of a
      formal diagnostic approach to the assessment of the severity of common
      psychiatric illnesses. Whilst developing a diagnostic tool to assess depressive
      symptoms, based on the ICD-10 classification of disease, we surveyed the current
      usage of such diagnostic aids by general practitioners (GPs) in Birmingham.
      According to the Birmingham Health Authority IT Directorate, 477 GP principals in
      the city had personal access to email at their practices through the NHSnet.
      METHOD: All GPs were sent a short questionnaire by email. They were asked to
      indicate their responses to four yes/no answers and return the email by pressing
      the 'Reply' icon. Non-respondents were then sent the questionnaire by post.
      RESULTS: We had a total response rate of 67%. We received an email response from
      105 GPs, or 22%. A further 216 out of a possible 372 GPs (58%) then responded by
      post. Forty-seven (22%) of the postal respondents had received the email, but 38
      of them had problems replying; 150 (69%) said that they had never seen the email.
      CONCLUSIONS: The overall response rate to the questionnaire suggests that the
      topic was considered sufficiently relevant for GPs to reply and was not the
      reason for the poor email response. There were no obvious differences in the
      answers to the questionnaire to suggest that the mental health topic had
      identified a separate email-using GP population. Although four out of every five
      Birmingham GPs have access to email, only one in five feels confident or
      competent to use it as a regular means of professional communication. It is not
      yet appropriate to use email as the only conduit for obtaining GP opinion.

PMID- 16274591
TI  - Diversity, equal access and information.
AB  - The overall aim of diversity is to ensure that every individual, whatever their
      differences, has fair and equitable access to health care and to employment based
      on clinical need and merit. This has advantages for staff by allowing them to
      give of their best and for patients by better identifying and meeting their
      needs. Evidence shows that individuals from minority groups are often not treated
      fairly and positive action is required to redress the balance.

PMID- 16274592
TI  - Why is ICRS so hard?

PMID- 16274594
TI  - Challenges of the EU 'tissues and cells' directive.
AB  - Assisted conception is among many tissue-processing disciplines encompassed by
      new European legislation on the quality and safety of tissues and cells used
      therapeutically. These directives have highlighted interdisciplinary differences
      in some current practices, such as variations in laboratory air quality. This
      commentary discusses the likely requirements of the EU directives for air quality
      in tissue-processing laboratories. It also draws attention to the concept of
      validation. Validation becomes essential to justify all processes, and would be
      an essential tool to support any deviations from normal 'Good Manufacturing
      Practices', such as adopting a lesser grade of laboratory air quality.

PMID- 16274595
TI  - Response to article -- 'A critical assessment of the impact of the European Union
      Tissues and Cell Directive (2004) on laboratory practices in assisted conception'
      by David Mortimer.
AB  - The European Union's Tissues and Cell Directive and the US regulations for tissue
      banks, both produced in 2004, recognize the need to revise current tissue
      processing activities and address related risks of infection. The principle
      behind these regulations and the Australian and New Zealand, Reproductive
      Technology Accreditation Committee (RTAC) Code of Practice, produced in 2005, are
      all similar with an underlying quality management theme. Each of these documents
      is based on the premise to safeguard public health in the prevention of
      transmission of infectious diseases via transplanted tissues and cells.

PMID- 16274596
TI  - LH improves early follicular recruitment in women over 38 years old.
AB  - Although the capacity of recombinant FSH alone to induce folliculogenesis is
      undisputed, many believe that follicular recruitment in women over 38 years old
      could be improved by supplementing rFSH with human menopausal gonadotrophin
      (HMG). The present study sought to determine whether recombinant LH could
      reproduce the effect of HMG in women over 38 years during ovulation induction.
      Fifty-eight patients received rFSH (225 IU/day) supplemented with one ampoule of
      HMG (75 IU of FSH/75 IU of LH/HCG per day) for 5 days. Another 36 patients
      received rFSH (300 IU/day) supplemented with one ampoule of rLH (75 IU/day), also
      for 5 days. Both groups of patients received similar amounts of rFSH (1500 IU),
      LH/HCG (375 IU) and rLH (375 IU) and recruited a similar number of follicles as
      counted on day 6 (4.07 +/- 3.1 in the HMG group versus 3.7 +/- 3.2 in the LH
      group respectively) or on the day that human chorionic gonadotrophin (HCG) was
      indicated (6.5 +/- 2.7 versus 5.8 +/- 2.5 respectively). Ovarian stimulation was
      shorter, but not significantly so, in the group of patients receiving rFSH + HMG
      (10.5 +/- 1.7 days) than in the group of patients treated with rFSH +/- rLH (12
      +/- 1.8 days). Significantly more MII oocytes were seen in the group treated with
      rFSH + rLH than in the group treated with rFSH + HMG (93.1 versus 75.3%, P <
      0.05). With respect to pregnancy rates, 14/54 (26%) patients receiving rFSH + HMG
      and 16/34 (47%) patients receiving rFSH + rLH had a positive serum HCG. No
      significant difference in the number of miscarriages was observed between the two
      groups. In conclusion, the present results seem to indicate that rLH could be the
      HMG component that aids early follicular recruitment.

PMID- 16274597
TI  - Use of a fully automated injector for self-administration of follitropin alpha in
      an IVF/ICSI programme.
AB  - Recombinant FSH (r-FSH) used for ovarian stimulation can currently be self
      administered either by a conventional syringe or by a pen device. This randomized
      controlled trial compares the efficacy and convenience of a new, more
      sophisticated and fully automated injection device (Softinject(trade mark)) with
      the conventional syringe for r-FSH self-administration. A total of 300 women
      needing ovarian stimulation for IVF/intracytoplasmic sperm injection were
      randomized to the automated injector or the conventional syringe group. Patients
      of both groups had ovarian stimulation with follitropin alpha after pituitary
      desensitization with a gonadotrophin-releasing hormone agonist. State anxiety
      score, overall pain score and pregnancy rate were chosen as the main outcome
      measures. Patients in the automated injector group showed lower state anxiety (P
      < 0.01) and overall pain (P < 0.01) scores and a comparable pregnancy rate per
      started cycle as compared with the conventional syringe group. They needed lower
      doses of r-FSH (P < 0.05) and their stimulation was shorter (P < 0.05). It is
      concluded that the use of a fully automated injector for r-FSH self
      administration reduces pain and stress as compared with the conventional syringe.
      This device can be used for any subcutaneously administered drug employed in
      ovarian stimulation.

PMID- 16274599
TI  - Criteria to assess human oocyte quality after cryopreservation.
AB  - Oocyte cryopreservation certainly represents one of the most attractive
      developments in the field of assisted reproduction, with the aim of preserving
      female fertility and circumventing the ethical and legal drawbacks associated
      with embryo freezing. Despite the achievement of the first pregnancy from frozen
      oocytes dating back as early as 1987, since then fewer than 150 pregnancies have
      been reported. Over a long period of time, application of oocyte storage on a
      large scale has been prevented by various factors, namely poor post-thaw
      survival. Fertilization rates remained low even after the introduction of
      intracytoplasmic sperm injection. Modifications of slow-freezing protocols,
      mainly based on the increase of the concentration of sucrose used as non
      penetrating cryoprotectant (CPA) and the replacement of sodium with choline,
      appear to have decisively improved survival rates to over 80%. Investigations at
      the cellular level on thawed oocytes are largely lacking. Fertilization rates
      have also benefited from protocol modifications, reaching values
      indistinguishable from those normally obtained with fresh material. Vitrification
      protocols have also been tested, giving rise to improvements whose
      reproducibility is still uncertain. Data on the dynamics of fertilization and
      preimplantation development of embryos derived from frozen oocytes are extremely
      scarce. At the moment, clinical efficiency of oocyte cryopreservation cannot be
      precisely assessed because of the lack of controlled studies, although it appears
      to be considerably lower than that achieved with embryo freezing. In summary,
      encouraging advances have been made in the field of oocyte cryopreservation, but
      presently no protocol can ensure standards of success and safety comparable to
      those guaranteed by embryo storage.

PMID- 16274600
TI  - Freeze-thaw programmes rescue the implantation of day 6 blastocysts.
AB  - The developmental rate of a blastocyst is considered one of the main estimates
      for evaluating the implantation potential of embryos. Day 6 blastocysts have been
      reported to be much less viable than day 5 blastocysts. Regarding implantation,
      the implantation window is advanced due to a background of high sex hormones, and
      slower growing embryos may not implant because of possible desynchrony with the
      implantation window. The aim of this study was to investigate the efficacy of
      cryopreservation of such embryos and subsequent synchronization of embryo
      transfer with endometrial status. The results of 122 day 6 blastocysts
      transferred in the clinic were retrospectively examined. Pregnancy rates were
      compared between the stimulation cycle and hormone replacement cycle in terms of
      the method of endometrial preparation. Fifty-five day 6 blastocysts were
      transferred onto the stimulation cycle endometrium in 37 women, resulting in a
      5.5% viable pregnancy rate. On the other hand, 67 day 6 blastocysts were
      transferred onto endometrium prepared by exogenous hormones in 40 women,
      resulting in a 26.9% viable pregnancy rate (P < 0.01). Consequently, the
      difference was highly significant. In conclusion, synchronous transfer of slow
      growing embryos using the freeze-thaw technique contributes to a positive
      outcome.

PMID- 16274602
TI  - Vitrification of human 8-cell embryos, a modified protocol for better pregnancy
      rates.
AB  - Human day 3 embryos were vitrified in modified ethylene glycol-based protocol.
      The present study reports a post-thaw survival rate of 95.3%, which was
      significantly higher than that of the conventional slow-freezing protocol (60.0%,
      P < 0.05). The implantation and pregnancy rates were also higher (14.9% and
      35.0%) than that in the slow-freezing protocol (4.2% and 17.4%). On average,
      three embryos were transferred per patient. Out of the 40 transfer cycles, five
      deliveries and nine ongoing pregnancies were achieved. Four ended with delivery
      of a singleton and one a miscarriage. Ethylene glycol is a good cryoprotectant to
      preserve human 8-cell embryos because of its low toxicity as shown by the high
      survival rate, and vitrification is a promising alternate to the conventional
      slow-freezing method.

PMID- 16274603
TI  - Effect of oxygen concentration during the incubation of embryos of women
      undergoing ICSI and embryo transfer: a prospective randomized study.
AB  - The hypothesis that ICSI outcome can be improved by culturing human embryos in an
      atmosphere of controlled O(2) concentration (5%) compared with 20% was tested in
      a prospective randomized study of 712 transfer cycles. The cycle characteristics
      and the embryology parameters were similar between groups. The embryo qualities
      were similar with day 2 transfers; however, they were better with day 3 transfers
      incubated in 5% O(2) than in 20% O(2). The clinical outcome parameters did not
      differ between groups according to the O(2) concentration. The results indicated
      that culture of embryos under atmospheric conditions of O(2) for the first 2 or 3
      days did not alter the clinical outcome in ICSI cycles.

PMID- 16274605
TI  - Screening of the galactose-1-phosphate uridyltransferase gene in Indian women
      with ovarian failure.
AB  - The present study was aimed at mutational screening of the gene coding for
      galactose-1-phosphate uridyltransferase in females with premature ovarian failure
      within an Indian population. A case-control-based study approach was used. It
      included females with premature ovarian failure (n = 108), primary amenorrhoea (n
      = 37) and secondary amenorrhoea (n = 9), and a control group of 136 women with a
      normal ovarian pattern. Gene sequencing analysis for the presence of mutations in
      the promoter and the coding regions of GALT has shown the absence of any
      mutation. A hexanucleotide deletion was found in the third intronic region of
      GALT in both cases and controls. These data support the hypothesis that there is
      no significant association between GALT mutations and ovarian failure, and hence
      the present authors conclude that there is no relationship between ovarian
      failure and GALT polymorphisms in Indian women.

PMID- 16274606
TI  - Successful birth after injection of frozen human oocytes with frozen epididymal
      spermatozoa.
AB  - A couple (female 31, male 42 years old) with infertility due to obstructive
      azoospermy returned to the clinic in order to attempt pregnancy using their
      frozen oocytes and epididymal sperm cells, which had been cryopreserved at the
      time of a previous IVF attempt. Two days before the scheduled transfer, eight
      oocytes were thawed; 5/8 (63%) oocytes survived and 4/5 (80%) oocytes fertilized
      after intracytoplasmic sperm injection (ICSI) with the previously frozen
      epididymal spermatozoa. All four fertilized ova cleaved (100%). On day 2 after
      thawing, four embryos were transferred; three with two cells (grade II) and one
      with three cells (grade III). Hormonal support for the established pregnancy was
      maintained with oestradiol and progesterone orally until 12 weeks of gestation,
      and the patient was delivered by Caesarean section at 40 weeks of gestation; the
      baby boy weighed 3025 g, and measured 51 cm, with Apgar of 10 in the 1st and 5th
      min. The cryopreservation and warming protocol used for this study yielded very
      favourable results, comparing well with reports in the literature. This case
      report demonstrates that it is possible to obtain high rates of oocyte survival
      following thawing and high rates of fertilization after ICSI, with viable
      development of the resulting embryos.

PMID- 16274607
TI  - Live birth after IVF in a 46-year-old woman.
AB  - Pregnancies after IVF have been reported in women aged > or =44 years, but nobody
      older than 45 years at oocyte retrieval delivered. We report a case of birth of a
      healthy child after IVF in a 46-year-old infertile woman. Ovarian stimulation was
      performed with clomiphene citrate, 150 mg daily for 5 days. Three oocytes were
      retrieved and one embryo was replaced. The patient delivered a healthy male
      infant after Caesarean section at 39 weeks. A successful pregnancy after IVF with
      homologous oocytes can be achieved in women older than 45 years. At this age IVF
      is not a cost-effective treatment compared with oocyte donation, but it may be
      offered in countries in which gamete donation is forbidden.

PMID- 16274608
TI  - Successful treatment of an aggressive recurrent post-menopausal endometriosis
      with an aromatase inhibitor.
AB  - The current case report describes the development and medical treatment of an
      aggressive pelvic endometrioma in a post-menopausal patient, who had undergone
      abdominal hysterectomy and salpingo-oophorectomy a decade earlier. The patient
      was referred to the authors' centre because of right-sided sciatic pain. Three
      months before her admission she was hospitalized elsewhere due to subacute bowel
      obstruction. She was operated on and a resection of a part of sigmoid colon and
      an endometrioma, which was the cause of the subobstruction, was carried out.
      During the clinical investigation for the right-sided sciatic pain, an
      intrapelvic mass was found, which was compressing the lumbo-sacral plexus
      mimicking sciatica. The diagnosis of recurrent endometrioma was confirmed by a
      computerized tomography-guided biopsy and the decision was made to treat it with
      an aromatase inhibitor (letrozole). Eighteen months later, the endometrioma was
      almost completely regressed and the patient was free of symptoms. Medical
      management of recurrent post-menopausal endometriosis with aromatase inhibitors
      seems to be an effective alternative treatment to surgery.

PMID- 16274609
TI  - Long-term follow-up of women and men after unsuccessful IVF.
AB  - The experience of 92 couples, who had unsuccessfully undergone one or more IVF
      cycles at a university clinic, was evaluated 3-8 years following their last
      failed attempt. One member of each couple completed a telephone questionnaire
      regarding life events during their last IVF cycle performed at the clinic and at
      the time of the interview. Some couples had continued further treatment and some
      had not. Multivariate correspondence analysis was used to analyse the data.
      Regarding the long-term experience of couples who had undergone further
      treatment, for men the main experiences were psychological problems and having
      adopted a child. For women, the main experiences were related to problems of self
      image, psychological problems, loss of hope, and having adopted a child. These
      women also presented a strong association with problems in their marital
      relationship and with adoption. For the group that did not undergo further
      treatment, the women showed a strong association with considering adoption, and a
      less intense association with psychological problems and loss of hope. The men
      presented psychological problems and having adopted a child as associated
      variables. Comparison between men and women showed that recognizing the
      impossibility of conceiving a child and giving up treatment were strongly
      associated. Men and women who had not continued with further treatment were more
      affected in the long term than those who had undergone further treatment after
      IVF failure.

PMID- 16274610
TI  - Implantation markers and endometriosis.
AB  - The receptive phase of the endometrium seems to occur in close association with
      the appearance of pinopodes and endometrial integrins that may be activated by
      the interleukin-1 system (IL-1). Embryo attachment is the result of adhesion
      protein expression, and the invasion of the embryo is governed by proteolytic
      enzymes. Leukaemia inhibitory factor (LIF) is produced by natural killer
      lymphocytes that interact with the invading trophoblast. This may activate
      urokinase plasminogen activator (uPA) and gelatinase enzymes, which play a
      crucial role in trophoblast invasion. Oestrogen stimulates, while progesterone
      inhibits, LIF. The role of endometrial contractility in displacing human embryos
      from the Fallopian tube to the lumen cavity of the uterus or vagina in terms of
      pregnancy or wastage is still a matter of discussion. Endometriosis and its
      associated abnormal uterine contractions may be also linked to implantation
      failure. Unless new evidence emerges to indicate otherwise, it can be assumed
      that progesterone is, either in a direct (non-genomic: contractility) or indirect
      (genomic: decidualization) manner, the only determinant of endometrial priming
      necessary for embryo nidation.

PMID- 16274611
TI  - Neonatal and obstetric outcome of pregnancies conceived by ICSI or IVF.
AB  - Intracytoplasmic sperm injection (ICSI) is currently widely used despite concern
      regarding pregnancy complications and outcome, specifically congenital
      malformations. The aim of this study was to compare the obstetric and neonatal
      outcome of pregnancies conceived by IVF and ICSI. Long-term follow-up was
      achieved through questionnaires sent to women who conceived after IVF/ICSI
      treatment. Information was obtained regarding 219 pregnancies (322 children)
      conceived after ICSI and 145 pregnancies (201 children) conceived after IVF.
      There were no significant differences between the ICSI and regular IVF
      pregnancies in regard to the couple's characteristics and the obstetric
      complications. The mean +/- SD birth weight of the singletons conceived after
      ICSI was similar to that of singletons conceived after IVF: 3001 +/- 703 versus
      3059 +/- 643 g respectively. In both groups there was a high incidence of
      multiple pregnancies, Caesarean sections, prematurity and low birth weights. The
      incidence of congenital malformations following IVF or ICSI pregnancies was
      similar, 6.3 and 7.7% respectively, but was increased compared with the general
      Israeli population. In summary, concern remains regarding the incidence of
      congenital malformations after IVF and the long-term outcome of ICSI pregnancies.
      However, the present results are reassuring with regard to the obstetric and
      neonatal outcome of pregnancies conceived by ICSI compared with those achieved by
      IVF.

PMID- 16274613
TI  - Human embryonic stem cells: towards therapies for cardiac disease. Derivation of
      a Dutch human embryonic stem cell line.
AB  - Cell transplantation is being discussed as a potential therapy for multiple
      disorders caused by loss or malfunction of single or at most a few cell types.
      These include diabetes, Parkinson's disease and myocardial infarction or cardiac
      failure. However, it is not yet clear whether cells from adult tissues ('adult
      stem cells') or embryos ('embryonic stem cells') will prove to be the most
      appropriate replacement cells; most likely, each disease will have its own
      preferred source. This study presents the background to this discussion and the
      current state of research in replacement of cardiac tissue, with focus on recent
      developments using human embryonic stem cells. It also describes a new human
      embryonic stem cell (HESC) line, NL-HESC1, the first to be derived in the
      Netherlands, and shows that it forms cardiac cells in a manner comparable with
      that of hES2 and hES3 cells grown in the same laboratory.

PMID- 16274615
TI  - PGD patients' and providers' attitudes to the use and regulation of
      preimplantation genetic diagnosis.
AB  - Preimplantation genetic diagnosis (PGD) providers and patients have a vested
      interest in policy related to the use and regulation of PGD. To understand their
      experiences and attitudes, 32 in-depth interviews were conducted. Participants
      included 13 people at risk of transmitting a single-gene alteration to their
      children (10/13 had actually used PGD to try to have an unaffected child) and 19
      PGD service providers (four nurses, five genetic counsellors, two reproductive
      endocrinologists, two geneticists, two physician-geneticists, two embryologists,
      and two laboratory directors). Virtually all participants supported the use of
      PGD to avoid severe, life-threatening genetic illness or to select embryos that
      are a tissue match for a sick sibling, but their attitudes varied significantly
      over the appropriateness of using PGD to avoid adult-onset genetic disease, to
      select for sex, or to select for other non-medical characteristics. There was
      disagreement within the PGD provider community about whether or not PGD is
      experimental. Participants were more concerned about overzealous government
      regulation of PGD creating barriers to access than potential abuses of the
      technology, and expected the PGD provider community to take the lead in ensuring
      that PGD is used for ethically appropriate purposes.

PMID- 16274616
TI  - FISH screening of aneuploidies in preimplantation embryos to improve IVF outcome.
AB  - Preimplantation genetic diagnosis (PGD) has transformed the approach to the
      infertility patient in the IVF setting. Although the principal applications of
      PGD have been to prevent the transmission of sex-linked diseases, in time and
      with growing knowledge of the chromosomal abnormalities observed in
      preimplantation embryos, its applications have widened. Nowadays, apart from its
      implications in the prevention of transmission of chromosomal and genetic
      abnormalities, PGD is being used with increased frequency to improve the IVF
      outcome in patients with advanced maternal age (> or =38 years of age), recurrent
      miscarriage (> or =2 miscarriages), recurrent IVF failure (> or =3 failed IVF
      attempts) and severe male infertility. A high incidence of chromosomal
      abnormalities has been observed in these patient groups.

PMID- 16274617
TI  - Hormonal regulation of Leydig cell proliferation and differentiation in rodent
      testis: a dynamic interplay between gonadotrophins and testicular factors.
AB  - Studies over the last few decades have documented that LH is the principal
      regulator of Leydig cell function. Recent studies indicate that locally produced
      intratesticular factors are equally important in modulating Leydig cell
      development and function. In the present review, results of studies on Leydig
      development and function with rodent models, in conjunction with recent advances
      in our understanding, are discussed. Studies on Leydig cell development revealed
      that there are two different waves of proliferation: the first one is independent
      of LH and the other is dependent on LH. In addition to LH, FSH plays a major role
      in Leydig cell development and function by modulating the production of Sertoli
      cell-derived factors. Studies directed towards understanding the oestrogen
      mediated inhibition of Leydig cell proliferation revealed that collagen IV
      mediated signalling is involved in Leydig cell proliferation and 17beta
      oestradiol inhibits this event. Leydig cell proliferation and differentiation is
      associated with changes in gene expression. Research in this area has identified
      several genes that are involved in Leydig cell proliferation and differentiation;
      the possible role of these genes in the context of Leydig cell development are
      discussed in this review.

PMID- 16274619
TI  - The effectiveness of preimplantation genetic screening.

PMID- 16274621
TI  - The essential role of phosphoinositide 3-kinases (PI3Ks) in regulating pro
      inflammatory responses and the progression of cancer.
AB  - Phosphoinositide 3-Kinases (PI3Ks) are proteins coupled to a variety of cell
      surface receptors and play a key role in signal transduction cascade regulating
      fundamental cellular functions such as transcription, proliferation, and
      survival. PI3Ks also are important in disease processes such as inflammation and
      cancer. The aim of this review is to outline current understandings of the PI3K
      family, mechanism of their activation, their role in inflammatory responses and
      the development of malignant tumors.

PMID- 16274622
TI  - Distinct pattern of human Vdelta1 gammadelta T cells recognizing MICA.
AB  - Gammadelta T cells represent one unique recognition pattern, the limited
      recognition, which distinguishes from the specific recognition for alphabeta T
      cells and pattern recognition for macrophages. Vdelta1 gammadelta T cell is the
      major subset of human gammadelta T cells, which predominates in mucosal tissue
      including the intestinal epithelia. Presently, a few antigens that human
      Vdelta1TCR can recognize have been identified. Among them, MHC class I chain
      related molecules A (MICA) have been studied most intensively. Besides
      Vdelta1TCR, MICA is also the ligand of NKG2D, a C-type lectin-like activating
      immunoreceptor. In human, only Vdelta1 cells can simultaneously express both
      types of receptors of MICA while NK cells, alphabetaT cells and other subsets of
      gammadelta T cells likewise express NKG2D. Although the precise mechanisms are
      still enigmatic, this distinct pattern of Vdelta1 cells recognizing MICA predicts
      unique biological significance of Vdelta1 cells in immune defense. Recent years,
      some progresses have been made in this issue. In this review we summarize the
      related reports and put forward some novel views based on our group's studies.

PMID- 16274623
TI  - Molecular mechanisms of lymphocyte-mediated cytotoxicity.
AB  - Granule-mediated cytotoxicity is the major mechanism for lymphocytes to kill
      viruses, intracellular bacteria and tumors. The cytotoxic granules move to the
      immunological synapse by exocytosis after recognition of a killer cell. The
      contents of the granules are delivered into target cells with the help of
      perforin by endocytosis. A group of serine protease granzymes cleave their
      critical substrates to initiate DNA damage and cell death. The most abundant
      granzymes are granzyme A and B. They induce cell death through alternate and
      nonoverlapping pathways. The substrates and functions of the majority of the
      orphan granzymes have not yet been identified. It is possible that the diversity
      of granzymes provides fail-safe mechanisms for killing viruses and tumor cells.

PMID- 16274624
TI  - Current understanding on the immunological functions of tumor necrosis factor
      related apoptosis-inducing ligand.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively
      induces apoptosis in various tumor cells and virus-infected cells, but rarely in
      normal cells. The killing specificity of TRAIL has brought great interests to
      develop a novel apoptosis-based anti-tumor agent for clinical application. TRAIL
      is expressed in many normal tissues and cells, such as liver, brain, kidney,
      heart, colon, lung, and testis. However, immunological and physiological
      functions of TRAIL in vivo have not been understood well. In the present paper we
      summarized the progress in the research on immunological functions of TRAIL.

PMID- 16274625
TI  - Isolation of lymphocytes and their innate immune characterizations from liver,
      intestine, lung and uterus.
AB  - In steady-state conditions, the number and distribution of lymphocyte populations
      are under homeostatic control. New lymphocytes are continuously produced in
      primary and secondary lymphoid organs and then achieve immune-competence within
      different tissues, and they must challenge with resident cells for survival. The
      first step in the study of tissue lymphoid cells is their isolation in intact and
      viable form appropriate for establishment of in vitro culture systems. For
      reasons of simplicity, cell purity, cell yields and various purposes, lymphocytes
      obtained from different tissues in different labs were subjected to diverse
      protocols. To fully elucidate the nature of the local immune system as well as to
      adequately study the innate role of lymphocytes in liver, intestine, lung and
      uterus, we briefly reviewed the characterization of resident lymphocytes, and
      additional information on those cells from non-lymphoid tissues by using the
      recommended operation procedure was also presented.

PMID- 16274626
TI  - Gene transfer to dendritic cells induced a protective immunity against melanoma.
AB  - Lentiviral vectors have shown promises for efficient gene transfer to dividing as
      well as nondividing cells. In this study, we explored lentiviral vector-mediated,
      the entire mTRP-2 gene transfer and expression in dendritic cells (DCs). Adoptive
      transfer of DCs-expressing mTRP-2 (DC-HR'CmT2) into C57BL/6 mouse was also
      assessed. Dendritic cells were harvested from bone marrow and functional DCs were
      proved by allogeneic mixed lymphocyte reaction. Lentiviral vectors were produced
      by transient transfection of 293T cells. Transduction of DCs was proved by marker
      gene expression and PCR and RT-PCR amplification. Implantation of the transduced
      DCs, depletion of immune cells as well as the survival of the mice after tumour
      challenge were investigated. High efficiency of gene transfer into mature DCs was
      achieved. The high level expression of the functional antigen (TRP-2) and
      induction of protective immunity by adoptive transfer of TRP-2 gene modified DCs
      were demonstrated. In vivo study showed a complete protection of mice from
      further melanoma cell challenge. In comparison, only 83% of mice survived when
      mTRP-2 peptide-pulsed DCs were administered, suggesting the generation of
      specific protection. Together, these results demonstrated the usefulness of this
      gene transfer to DC approach for immunotherapy of cancer and indicated that using
      tumour associated antigens (TAAs) for gene transfer may be potentially beneficial
      for the therapy of melanoma.

PMID- 16274627
TI  - Immune responses to six synthetic peptides of capsid protein with sera from HIV-1
      infected individuals.
AB  - Many B cell epitopes within p24 of human immunodeficiency virus type 1 (HIV-1)
      were identified, while most of them were determined by using murine monoclonal
      antibodies reacting with overlapping peptides of p24. Therefore these epitopes
      may not represent the actual epitopes recognized by the HIV-1 infected
      individuals. In the present study, immune responses of 67 HIV-1 positive sera
      from Yunnan Province, China to five peptides on p24 of HIV-1 and one of HIV-2
      were analyzed. All of 67 sera did not recognize peptide GA-12 on HIV-1 and
      peptide AG-23 on HIV-2, which indicated that GA-12 was not human B cell epitope
      and AG-23 did not cross-react with HIV-1 positive serum. Except 13 sera (19.4%),
      all remaining sera did not recognize peptides NI-15, DR-16, DC-22 and PS-18,
      which indicated that these four peptides represented B cell linear epitopes of
      HIV-1 p24 in some HIV-1 infected individuals but not the immuno-dominant epitopes
      in most individuals.

PMID- 16274629
TI  - Thymic nurse cells support CD4-CD8+ thymocytes to differentiate into CD4+CD8+
      cells.
AB  - Thymic nurse cells (TNCs) represent a unique microenvironment in the thymus for T
      cell maturation. In order to investigate the role of thymic nurse cells during T
      cell differentiation, a TNC clone, RWTE-1, which formed a typical complex with
      fetal thymocytes in vitro was established from normal Wistar rat. Hanging drop
      culture method was applied to reveal the interaction between TNCs and thymocytes.
      Our result revealed that eighty percent of immature CD4(-)CD8(+) cells
      differentiated into CD4(+)CD8(+) cells after a 12-hour hanging drop culture with
      RWTE-1. However, in a 12-hour culture of immature CD4(-)CD8(+) cells with or
      without RWTE-1 supernatant, only 30% of the cells differentiated into
      CD4(+)CD8(+) cells spontaneously. This observation led to the conclusion that
      RWTE-1 cell has the capacity to facilitate immature CD4(-)CD8(+) thymocytes to
      differentiate into CD4(+)CD8(+) T cells by direct interaction.

PMID- 16274628
TI  - Inhibitory effects of berberine on the activation and cell cycle progression of
      human peripheral lymphocytes.
AB  - The immunosuppressive property of berberine, an isoquinoline alkaloid, has been
      well documented, but the mechanism of its action on lymphocytes has not been
      completely elucidated. The present study is to investigate the effect of
      berberine on the activation and proliferation of lymphocytes, in particular T
      lymphocytes. Whole peripheral blood from healthy donors was stimulated with
      phytohemagglutinin (PHA) alone or phorbol dibutyrate (PDB) plus ionomycin, and
      the expression of CD69 and CD25 on T lymphocytes was evaluated with flow
      cytometry. The distribution of cell cycles and cell viability were analyzed by
      staining with propidium iodide (PI) and 7-aminoactinomycin D (7-AAD),
      respectively. The results showed that 100 micromol/L and 50 micromol/L of
      berberine significantly inhibited CD69 expression on T cells stimulated with PDB
      plus ionomycin or PHA, whereas the effect of 25 micromol/L berberine was not
      significant. As the incubation time increased, the extent of inhibition
      decreased. Similarly, the expression of CD25 was also reduced by berberine in a
      dose-dependent manner over the concentration range of 25-100 micromol/L. Besides,
      this alkaloid could block lymphocyte cell cycle progression from G0/G1 phase to S
      and G2/M phase without phase specificity. Moreover, analysis following 7-AAD
      staining revealed that berberine had no significant cytotoxicity on lymphocytes.
      Taken together, berberine significantly inhibits the expression of activation
      antigens on T lymphocytes and also blocks the progression of cell cycles of
      lymphocytes, suggesting that berberine may exert immunosuppressive effect through
      inhibiting the activation and proliferation of T cells.

PMID- 16274630
TI  - B7-H3: another molecule marker for Mo-DCs?
AB  - Using a newly generated monoclonal antibody (2E6) against human B7-H3, we
      explored the expression of the molecule on dendritic cells derived from monocytes
      (Mo-DCs). Its expression was examined by means of immunostaining and flow
      cytometric (FCM) analysis. The results showed that B7-H3 was expressed in the
      course of Mo-DC maturation induced with interleukin 4 (IL-4) and
      granulocyte/macrophage colony-stimulating factor (GM-CSF). The expression could
      be detected at all the stages of Mo-DC differentiation, and remained at a quite
      stable level. Interestingly, B7-H3 was not expressed by T cells and B cells, even
      these cells were activated respectively by PHA or PWM. A weak expression could be
      detected on resting monocytes. These data showed that constitutive expression of
      B7-H3 at a high level was found on imDCs and mDCs derived from monocytes. Due to
      no expression on T cells and B cells, we speculate that B7-H3 might be another
      valuable molecule marker for Mo-DCs.

PMID- 16274632
TI  - [Advances in genetics: which benefits for the patients?].

PMID- 16274631
TI  - The effect of glycation of CD59 on complement-mediated cytolysis.
AB  - Vascular proliferation is one of the major causes for morbidity and mortality in
      diabetes. However, the cellular and molecular mechanisms that link hyperglycemia
      to this complication remain unclear. In present study, we demonstrated by site
      directed mutagenesis that mutated CD59 was more susceptible to glycation
      inactivation for hyperglycemia. Mutated and wild-type CD59s were stably expressed
      in Chinese hamster ovary cells using the pALTER-MAX mammalian expression vector.
      Western blot, FACS and immunological fluorescence were conducted to confirm that
      CD59s were tethered to the plasma membrane. Compared to wild-type CD59, human
      CD59 mutants led to a significant increase in dye release assay. These results
      indicate that there may be some mutations of CD59 in diabetes population and the
      mutated CD59, which is more likely to be of glycation than the wild-type, may
      help to explain the distinct propensity of diabetes subjects to develop vascular
      proliferation complications.

PMID- 16274633
TI  - [A late Neanderthal femur from Les Rochers-de-Villeneuve, France].

PMID- 16274634
TI  - [Structure of the Mg-chelatase cofactor GUN4 reveals a novel hand-shaped fold for
      porphyrin binding].

PMID- 16274635
TI  - [A variant in the CD209 (DC-SIGN) promoter is associated with severity of dengue
      disease].

PMID- 16274636
TI  - [Battle of the sexes with clonal reproduction by males and queens in an ant
      species].

PMID- 16274637
TI  - [Endocytosis: the Trojan Horse of viral infection].

PMID- 16274638
TI  - [HLA-DO: regulator of the immune response].

PMID- 16274639
TI  - [An unexpected role for agrin on cell-to-cell coupling during synaptogenesis].

PMID- 16274640
TI  - [A common somitic origin for embryonic muscle progenitors].

PMID- 16274641
TI  - [SUMO modification represses transcriptional activity of Sox proteins].

PMID- 16274643
TI  - [Multifactorial diseases: a nightmare for the geneticist].
AB  - Common diseases are often familial, but they do not show in most families, a
      simple pattern of inheritance. In a few families these diseases may be caused by
      a mutation in a single gene. In most families these diseases are multifactorial,
      they result from a complex interaction between a genetic component which is often
      polygenic and many environmental factors. Two major, model free, methods are used
      to locate and identify susceptibility genes that predispose to multifactorial
      diseases. The first is a non parametric linkage analysis that relies on affected
      sib pairs, or an affected pedigree member, the second method is association
      studies which looks for increase frequency of particular alleles or genotypes in
      affected compared with unaffected individuals in the population. Most of the
      results have not been replicated, identifying susceptibility genes is proving
      much more difficult than most geneticists imagined 20 years ago. The main reason
      for this irreproducibility is genetic heterogeneity.

PMID- 16274644
TI  - [Predictive testing: presymptomatic diagnosis in neurogenetic disorders].
AB  - Presymptomatic testing is available since 15 years for Huntington disease and it
      is now possible for a number of other neurogenetic disorders, mostly
      neurodegenerative disorders. The possibility of determining the genetic status of
      an at-risk person for the disorder which run in his family raises questions
      because of the absence of preventive and curative treatments in most instances.
      In addition, being carrier does not tell you when the disease will start and how
      it will evolve, impairing the possibilities of planning the future. A
      pluridisciplinary approach to predictive testing with care before, during and
      after the test taking into account the medical, social and psychological aspects
      of the disease is good practice. At the present time, only a minority of at-risk
      individuals request presymptomatic testing and almost 50 % do not pursue until
      the results. The consequences of the test may be harmful, more frequently after
      an unfavorable than after a favorable result. Although the motivations and the
      outcome in terms of request for prenatal testing after a carrier result are
      different in Huntington's disease and spinocerebellar ataxias, our experience
      underlines the benefit of pluridisciplinary care and of time for decision taking.
      For other disorders like familial Alzheimer's disease, or familial Creutzfeldt
      Jakob disease, the experience in presymptomatic testing is still limited but the
      situation seems similar to Huntington's disease because of the presence of
      dementia. It will be interesting to study the motivations and the outcome of the
      tests in disorders like autosomal dominant spastic paraplegias which usually do
      not reduce the life expectancy. Nevertheless, the overall situation might change
      greatly when efficient treatments will become available in these disorders.

PMID- 16274645
TI  - [New developments in cytogenetics].
AB  - Novel methods allowing to analyze the human genome make it possible to assess old
      questions such as the molecular basis of structural chromosome anomalies and the
      diathesis to aneuploidy. The architecture of the human genome as unravelled by
      the human genome sequencing project allows to explain the recurrence of
      microdeletions and microduplications caused by a non allelic homologous
      recombination involving segmental duplications created during the evolution of
      primates. This structural feature of the human genome is associated with a novel
      class of genetic diseases called genomic disorders as opposed to genetic diseases
      due to gene mutations. The study of the parental and cellular origin of
      aneuploidy shed new light on the different mechanisms controlling meiosis in man
      and woman. In addition it contributes to define the role of maternal age and
      genetic recombination on the behavior of chromosomes during meiosis. These new
      data greatly contribute to our understanding of human chromosomal diseases.

PMID- 16274646
TI  - [X-linked mental retardation].
AB  - X-linked mental retardation (XLMR) affects 1.8 per thousand male births and is
      usually categorized as "syndromic" (MRXS) or "non-specific" (MRX) forms according
      to the presence or absence of specific signs in addition to the MR. Up to 60
      genes have been implicated in XLMR and certain mutations can alternatively lead
      to MRXS or MRX. Indeed the extreme phenotypic and allelic heterogeneity of XLMR
      makes the classification of most genes difficult. Therefore, following
      identification of new genes, accurate retrospective clinical evaluation of
      patients and their families is necessary to aid the molecular diagnosis and the
      classification of this heterogeneous group of disorders. Analyses of the protein
      products corresponding to XLMR genes show a great diversity of cellular pathways
      involved in MR. Common mechanisms are beginning to emerge : a first group of
      proteins belongs to the Rho and Rab GTPase signaling pathways involved in
      neuronal differentiation and synaptic plasticity and a second group is related to
      the regulation of gene expression. In this review, we illustrate the complexity
      of XLMR conditions and present recent data about the FMR1, ARX and Oligophrenin 1
      genes.

PMID- 16274647
TI  - [Hereditary skeletal dysplasias and FGFR3 and PTHR1 signaling pathways].
AB  - Skeletal development is a highly sophisticated process involving, as a first
      step, migration and condensation of mesenchymal cells into osteoprogenitor cells.
      These cells further differentiate into chondrocytes and osteoblasts through
      multiple differentiation stages requiring a set of specific transcriptional
      factors. Defective endochondral ossification in human is associated with a large
      number of inherited skeletal dysplasias caused by mutations in genes encoding
      extracellular matrix components, growth factors and their receptors, signaling
      molecules and transcription factors. This review summarizes some of the recent
      findings on a series of chondrodysplasias caused by mutations in FGFR3 and PTHR1,
      two receptors expressed in the cartilage growth plate and mediating two main
      signaling pathways. Data from human diseases and relevant animal models provide
      new clues for understanding how signaling molecules and their interaction with
      key transcription factors control and regulate the development and growth of long
      bones.

PMID- 16274648
TI  - [Cancer genetic predisposition: current events and perspectives 2005].
AB  - Studies performed during these last twenty years have had a major impact on the
      understanding of carcinogenesis. They have opened a new field : cancer genetic
      predisposition. At the present time, most of the cancer predispositions linked to
      the alteration of one gene, associated with a high risk of cancer and with a
      specific phenotype have been identified. About 40 genes have been identified and
      have led to genetic testing. The indication of genetic testing, the management of
      at risk patients need the establishment of guidelines. The next challenge is the
      identification of cancer predisposing genes associated with low risk or modifying
      the effect of treatment.

PMID- 16274649
TI  - [Mutation mechanisms and their consequences].
AB  - The identification of mutations leading to human genetic diseases has grown into
      an intensive research field during the last few years. Through novel DNA analysis
      progress, it is now possible to determine the mutational spectrum for a given
      genetic disease and international databases are now available online. Genetic
      diagnosis of hereditary diseases has become an essential tool in genetic
      counselling and prenatal diagnosis. The knowledge of the deleterious mutation
      type and the molecular associated mechanism is fundamental in order to devise the
      optimal molecular diagnosis strategy. This review aims to present the various
      mutation categories involved in genetic diseases (single base-pair substitutions,
      small deletions or insertions, dynamic mutations, gross DNA lesions...) and to
      summarize our current knowledge about the main molecular mechanisms responsible
      for these mutations. Their deleterious consequences on gene expression, including
      transcription and transcript maturation, and protein loss or gain of function are
      also discussed in this review.

PMID- 16274651
TI  - [Prenatal and preimplantation genetic diagnosis: decision tree, new practices?].
AB  - Preimplantation genetic diagnosis (PGD) purpose is to assess the genetic status
      of 3 day-old embryos. PGD offers thus to couples "at-risk" of a genetic disorder
      an earlier option to prenatal diagnosis (PND). At the beginning, PGD's
      indications, patients and law were very closed to PND, but PGD specificities are
      gradually raising. Particularly, indications vary considerably in countries where
      the absence of law authorizes all the practices. Some of these applications are
      moreover raising serious ethical issues. Even in France, where this activity is
      particularly supervised, the recent modification to the law marks this evolution.

PMID- 16274650
TI  - [Radiological innovations in the screening and diagnosis of the inborn errors of
      metabolism].
AB  - New metabolic diseases are regularly identified by a genetic or biochemical
      approach. Indeed, the metabolic diseases result from an enzymatic block with
      accumulation of a metabolite upstream to the block and deficit of a metabolite
      downstream. The characterization of these abnormal metabolites by MRI
      spectroscopy permitted to identify the deficient enzyme in two new groups of
      diseases, creatine deficiencies and polyol anomalies. Creatine deficiency is
      implicated in unspecific mental retardation. A low peak of creatine at MRI
      spectroscopy is evocating of creatine deficiency which is treatable by creatine
      administration. Deficiency of synthesis of polyols, metabolites on the pentose
      pathway, represent new described metabolic diseases with variable symptoms
      including a neurological distress, liver disease, splenomegaly, cutis laxa and
      renal insufficiency. The deficit of ribose-5-phosphate isomerase, one of the
      enzymes whose diagnosis is evoked in front of the accumulation of ribitol,
      arabitol and xylitol leads to a leucodystrophy in adults. This new deficit was
      highlighted by the identification of an abnormal peak in cerebral MRI
      spectroscopy corresponding to the abnormal accumulation of polyols in brain.
      Congenital hyperinsulinism (HI) is characterized by profound hypoglycaemia
      related to inappropriate insulin secretion. Focal and diffuse forms of
      hyperinsulinism share a similar clinical presentation but their treatment is
      dramatically different. Until recently, preoperative differential diagnosis was
      based on pancreatic venous sampling, an invasive and technically demanding
      technique. Positron emission tomography (PET) after injection of [18F]Fluoro-L
      DOPA has been evaluated for the preoperative differentiation between focal and
      diffuse HI, by imaging uptake of radiotracer and the conversion of [18F]Fluoro-L
      DOPA into dopamine by DOPA decarboxylase. PET with [18F]Fluoro-L-DOPA has been
      validated as a reliable test to differentiate diffuse and focal HI and is now a
      major differential diagnosis tool in infantile hyperinsulinemic hypoglycaemia.

PMID- 16274652
TI  - [The Nobel Prize in Medicine, 2005. Barry J. Marshall and J. Robin Warren.
      Helicobacter pylori honored].

PMID- 16274653
TI  - [Nobel Prize in Chemistry, 2005. Yves Chauvin, Robert H. Grubbs and Richard R.
      Schrock. Metathesis and catalysis honored].

PMID- 16274654
TI  - [Sharing of biotechnology: contractual agreements as avant-garde].
AB  - In the face of growing exclusivist strategies that tend to hamper research and
      undermine equity, sharing imperatives have become a cornerstone of biotechnology
      development. Whereas a proliferation of laws and conventions now require the
      sharing of biological resources and knowledge as well as the sharing of benefits,
      contractual agreements more and more appear as a most useful tool to implement
      these requirements.

PMID- 16274655
TI  - [Snuppy from Korea].

PMID- 16274656
TI  - [Neither genes, nor junk, but... TAR/TUF!].

PMID- 16274657
TI  - [Fasting duration before elective abdominal surgery].

PMID- 16274658
TI  - Characterization of cathepsin L secreted by Sf21 insect cells.
AB  - Sf21 cells, derived from the Spodoptera frugiperda pupa, are commonly used for
      the heterologous expression of proteins. While purifying recombinant proteins
      from this system we encountered a protease, secreted at high levels by Sf21
      cells, that readily degraded recombinant proteins and also tended to co-purify
      with histidine-tagged proteins from Ni(2+) affinity columns. Purification and
      characterization of the protease revealed that it has many properties consistent
      with cysteine proteases of the papain family, including autoactivation under
      reducing conditions and acidic pH, and inhibition by E-64. Amino acid sequence
      analysis showed that the Sf21 enzyme may be identical to a putative insect
      procathepsin L cloned from the cotton bollworm. The subsite specificity of the
      Sf21 cathepsin and its inhibition profile by cystatins are consistent with the
      protease being an insect homologue of cathepsin L. Monoclonal antibodies useful
      for the detection and purification of the insect cathepsin L were developed.

PMID- 16274659
TI  - Trp-262 is a key residue for the hydrolytic and transglucosidic reactivity of the
      Aspergillus niger family 3 beta-glucosidase: substitution results in enzymes with
      mainly transglucosidic activity.
AB  - Trp-262 of the Aspergillus niger family 3 beta-glucosidase is shown in this
      report to be a key residue for determining the ratio of this enzyme's hydrolytic
      and transglucosidic activities. TLC showed that when cellobiose was both the
      substrate and the acceptor, beta-glucosidases with substitutions (Phe, Ala, Leu,
      and Cys) for Trp-262 formed very high amounts of transglucosidic adducts. When
      pNPGlc was the substrate and the acceptor of the substituted beta-glucosidases,
      only transglucosidic adducts and pNP were produced. Little or no Glc could be
      detected, indicating that the reactions occurring were mainly transglucosidic.
      GLC studies with cellobiose quantitatively showed that one Glc was transferred
      for each free Glc produced. Since this is the maximum level of transglucosidation
      possible, this again showed that the reaction is predominantly transglucosidic.
      Analyses of the K(m) and K(i) values of cello-oligosaccharides of increasing
      length, of the K(i) values of Glc and of the transglucosidic activity at low
      acceptor concentration, showed that substitution for Trp-262 causes poor binding
      at the binding site for the non-reducing Glc of the substrate while the affinity
      for other Glc units is only minimally affected. The acceptor sites become
      saturated with substrate (acceptor) at the concentrations needed for glucosidic
      bond cleavage and thus only transglucosidic reactions occur. In addition, the
      data indicate that substitution for Trp-262 causes the rate of the hydrolysis
      step (k(3)) to be small.

PMID- 16274660
TI  - Growth of miniature pig parotid cells on biomaterials in vitro.
AB  - Both Sjogren's syndrome and therapeutic irradiation for head and neck cancer lead
      to irreversible damage of the parenchyma of the salivary glands. This report
      describes an attempt to grow miniature pig (minipig) parotid gland cells on
      artificial films and tubular scaffolds with the ultimate intention of developing
      bio-engineered replacement tissue. Minipig parotid cells were isolated and
      cultured. The growth and structural and physiological features of the cells which
      were cultured on films and porous tubular scaffolds made from poly(ethylene
      glycol)-terephthalate (PEGT)/poly(butylene terephthalate) (PBT) were examined. By
      9 days, the parotid cells on the films and the tubular scaffolds formed
      continuous monolayers. The secretory granules and nuclei of the cultured acinar
      cells remained polarised. Desmosomes, gap junctions and tight-like junctions were
      still present between the apical regions of adjacent cells. Amylase activity
      decreased during the culture period but was still evident in the medium after 10
      days of culture. In conclusion, minipig parotid cells are well-maintained in
      vitro on both a flat surface and a three-dimensional (3D) scaffold. The addition
      of a Matrigel coating to the surface of synthetic materials aids cell growth and
      maintenance of a morphology that more closely resembles normal epithelium.

PMID- 16274661
TI  - The structural relation between disgust sensitivity and blood-injection-injury
      fears: a cross-cultural comparison of US and Dutch data.
AB  - A growing body of literature has implicated the role of disgust sensitivity in
      blood-injection-injury (BII) phobia. The present study sought to extend this line
      of research by investigating the structural relation between Rozin et al.'s
      [(2000). Disgust. In M. Lewis, J.M. Haviland (Eds.), Handbook of emotions. New
      York: Guilford Publications.] theoretical model of core and animal reminder
      disgust as they relate to BII fears in US (N = 162) and Dutch (N = 260) samples.
      Using confirmatory factor analysis (CFA), the hypothesized relation between the
      theoretical model of disgust and BII fears demonstrated good model fit in both
      samples. Consistent with previous findings on the differential relation between
      core and animal reminder disgust and BII fears [de Jong, P. J., & Merckelbach H.
      (1998). Blood-injection-injury phobia and fear of spiders: Domain specific
      individual differences in disgust sensitivity. Personality and Individual
      Differences, 24, 153-158], structural equation modeling (SEM) provided support
      for a domain specific relationship in both samples: animal reminder disgust was
      specifically related to the BII latent factor, whereas core disgust was not. The
      clinical and research implications regarding the relationships between disgust
      and BII fears across cultures are discussed.

PMID- 16274662
TI  - Diethyldithiocarbamate inhibits in vivo Cu,Zn-superoxide dismutase and perturbs
      free radical processes in the yeast Saccharomyces cerevisiae cells.
AB  - Copper-zinc superoxide dismutase (Cu,Zn-SOD) and manganese superoxide dismutase
      (Mn-SOD) in some model experiments in vitro demonstrated antioxidant as well as
      pro-oxidant properties. In the present study, yeast Saccharomyces cerevisiae
      lacking Mn-SOD were studied using Cu,Zn-SOD inhibitor N-N'-diethyldithiocarbamate
      (DDC) as a model system to study the physiological role of the yeast Cu,Zn-SOD.
      Yeast treatment by DDC caused dose-dependent inhibition of SOD in vivo, with 75%
      inhibition at 10mM DDC. The inhibition of SOD by DDC resulted in modification of
      carbonylprotein levels, indicated by a bell-shaped curve. The activity of
      glutathione reductase, isocitrate dehydrogenase, and glucose-6-phosphate
      dehydrogenase (enzymes associated with antioxidant) increased, demonstrating a
      compensatory effect in response to SOD inhibition by different concentrations of
      DDC. A strong positive correlation (R2=0.97) was found between SOD and catalase
      activities that may be explained by the protective role of SOD for catalase. All
      observed effects were absent in the isogenic SOD-deficient strain that excluded
      direct DDC influence. The results are discussed from the point of view that in
      vivo Cu,Zn-SOD of S. cerevisiae can demonstrate both anti- and pro-oxidant
      properties.

PMID- 16274663
TI  - The ABP-120 C-end region from Entamoeba histolytica interacts with sulfatide, a
      new lipid target.
AB  - EhABP-120 is the first filamin identified in the parasitic protozoan Entamoeba
      histolytica. Filamins are a family of cross-linking actin-binding proteins that
      promote a dynamic orthogonal web. They have been reported to interact directly
      with more than 30 cellular proteins and some phosphoinositides. The biochemical
      consequences of these interactions may have either positive or negative effects
      on the cross-linking function and also form a link between the cytoskeleton and
      plasma membrane. In this study, the EhABP-120 carboxy-terminal domain (END) was
      biochemically characterized. This domain was able to associate to 3-sulfate
      galactosyl ceramide, a new lipid target for a member of the filamin family. Also,
      the END domain was able to dimerize "in vitro." Molecular modeling analysis
      showed that the dimeric region is stabilized by a disulfide bond. Electrostatic
      and docking studies suggest that an electropositive concave pocket at the dimeric
      END domain interacts simultaneously with several sulfogalactose moieties of the
      sulfatide.

PMID- 16274664
TI  - Cloning, expression, and characterization of sialic acid synthases.
AB  - The most commonly occurring sialic acid, N-acetylneuraminic acid, is the
      repeating unit in polysialic acid chain of human neuronal cell adhesion molecule
      as well as in capsular polysialic acid of neuroinvasive bacteria, Escherichia
      coli K1 and Neisseria meningitidis. Sialic acid synthesis and polymerization
      occur in slightly different pathways in animals and bacteria. N-Acetylneuraminic
      acid (NeuNAc) is synthesized by the condensation of phosphoenolpyruvate and N
      acetylmannosamine by NeuNAc synthase in bacteria. The mammalian homologue N
      acetylneuraminic acid-9-phosphate (NeuNAc-9-P) synthase uses N-acetylmannosamine
      6-phosphate in the condensation reaction to produce NeuNAc-9-P. Both subfamilies
      of sialic acid synthases possess N-terminal triosephosphate isomerase barrel
      domain and C-terminal antifreeze protein domain. We report cloning of the genes,
      expression, purification, and characterization of human NeuNAc-9-P synthase and
      N. meningitidis NeuNAc synthase. Stability of the purified enzymes and effects of
      pH and temperature on their activities were evaluated. Enzyme kinetics and
      preliminary mutagenesis experiments reveal the importance of C-terminal
      antifreeze protein domain and a conserved cysteine residue for the enzyme
      activities.

PMID- 16274665
TI  - A new family of insect tyramine receptors.
AB  - The Drosophila Genome Project database contains a gene, CG7431, annotated to be
      an "unclassifiable biogenic amine receptor." We have cloned this gene and
      expressed it in Chinese hamster ovary cells. After testing various ligands for G
      protein-coupled receptors, we found that the receptor was specifically activated
      by tyramine (EC(50), 5x10(-7)M) and that it showed no cross-reactivity with beta
      phenylethylamine, octopamine, dopa, dopamine, adrenaline, noradrenaline,
      tryptamine, serotonin, histamine, and a library of 20 Drosophila neuropeptides
      (all tested in concentrations up to 10(-5) or 10(-4)M). The receptor was also
      expressed in Xenopus oocytes, where it was, again, specifically activated by
      tyramine with an EC(50) of 3x10(-7)M. Northern blots showed that the receptor is
      already expressed in 8-hour-old embryos and that it continues to be expressed in
      all subsequent developmental stages. Adult flies express the receptor both in the
      head and body (thorax/abdomen) parts. In addition to the Drosophila tyramine
      receptor gene, CG7431, we found another closely related Drosophila gene, CG16766,
      that probably also codes for a tyramine receptor. Furthermore, we annotated
      similar tyramine-like receptor genes in the genomic databases from the malaria
      mosquito Anopheles gambiae and the honeybee Apis mellifera. These four tyramine
      or tyramine-like receptors constitute a new receptor family that is
      phylogenetically distinct from the previously identified insect
      octopamine/tyramine receptors. The Drosophila tyramine receptor is, to our
      knowledge, the first cloned insect G protein-coupled receptor that appears to be
      fully specific for tyramine.

PMID- 16274666
TI  - Aminoacylase I deficiency: a novel inborn error of metabolism.
AB  - This is the first report of a patient with aminoacylase I deficiency. High
      amounts of N-acetylated amino acids were detected by gas chromatography-mass
      spectrometry in the urine, including the derivatives of serine, glutamic acid,
      alanine, methionine, glycine, and smaller amounts of threonine, leucine, valine,
      and isoleucine. NMR spectroscopy confirmed these findings and, in addition,
      showed the presence of N-acetylglutamine and N-acetylasparagine. In EBV
      transformed lymphoblasts, aminoacylase I activity was deficient. Loss of activity
      was due to decreased amounts of aminoacylase I protein. The amount of mRNA for
      the aminoacylase I was decreased. DNA sequencing of the encoding ACY1 gene showed
      a homozygous c.1057 C>T transition, predicting a p.Arg353Cys substitution. Both
      parents were heterozygous for the mutation. The mutation was also detected in
      5/161 controls. To exclude the possibility of a genetic polymorphism, protein
      expression studies were performed showing that the mutant protein had lost
      catalytic activity.

PMID- 16274667
TI  - Improved gene expression in resting macrophages using an oligopeptide derived
      from Vpr of human immunodeficiency virus type-1.
AB  - Vpr, an accessory gene product of human immunodeficiency virus type-1, is thought
      to transport a viral DNA from the cytoplasm to the nucleus in resting
      macrophages. Previously, we reported that a peptide encompassing amino acids 52
      78 of Vpr (C45D18) promotes the nuclear trafficking of recombinant proteins that
      are conjugated with C45D18. Here, we present evidence that C45D18, when
      conjugated with a six-branched cationic polymer of poly(N,N
      dimethylaminopropylacrylamide)-block-oligo(4-aminostyrene) (SV: star vector),
      facilitates gene expression in resting macrophages. Although there was no
      difference between SV alone and C45D18-SV with respect to gene transduction into
      growing cells, C45D18-SV resulted in more than 40-fold greater expression of the
      exogenous gene upon transduction into chemically differentiated macrophages and
      human quiescent monocyte-derived macrophages. The data suggest that C45D18
      contributes to improving the ability of a non-viral vector to transduce
      macrophages with exogenous genes and we discuss its further application.

PMID- 16274668
TI  - How accurately can we discriminate G-protein-coupled receptors as 7-tms TM
      protein sequences from other sequences?
AB  - The group of 2502 transmembrane (TM) protein sequences with seven TM segments (7
      tms) registered in SWISS-PROT 46.0 contains 2200 G-protein-coupled receptors
      (GPCRs), indicating that GPCR candidates can be detected with a reliability of
      87.9% in the eukaryotic genomes merely by correctly predicting the number of TM
      segments as 7-tms. The predictive accuracies of TM topology-prediction methods
      proposed so far are not as high as expected; even the best method, HMMTOP 2.0,
      can only achieve a capture rate of 7-tms sequences of 77.6%. It is necessary to
      improve this performance as much as possible, even if by only a few percentage
      points, in order to identify as many novel GPCR candidate genes as possible among
      the increasing number of newly sequenced genomes. In this study, we propose a
      simple but useful prediction method for detecting as many 7-tms TM protein
      sequences as GPCR candidates in eukaryotic genomes as possible. This is achieved
      by employing a two-step prediction procedure. The first step involves collecting
      7-tms sequences by the best prediction method (HMMTOP 2.0), and the second
      involves picking up the remaining 7-tms sequences by the second-best method
      (TMHMM 2.0). By this procedure, the capture rate of 7-tms TM protein sequences in
      SWISS-PROT can be improved considerably from 77.6% to 84.5%, and the number of
      GPCR candidate sequences predicted as 7-tms in the human genome (Build 35) is
      increased from 790 (by HMMTOP 2.0) to 903. These 790 and 903 candidate sequences
      include, respectively, 587 and 636 of the known human GPCRs of the 717 registered
      in SWISS-PROT 46.0, demonstrating that the proposed combinatorial method is
      effective in detecting GPCR candidate genes in eukaryotic genomes.

PMID- 16274669
TI  - Cystathionine beta-synthase is enriched in the brains of Down's patients.
AB  - Down's syndrome (DS) or trisomy 21 is the most common genetic cause of mental
      retardation, and adults with DS develop Alzheimer type of disease (AD).
      Cystathionine beta-synthase (CBS) is encoded on chromosome 21 and deficiency in
      its activity causes homocystinuria, the most common inborn error of sulfur amino
      acid metabolism and characterized by mental retardation and vascular disease.
      Here, we show that the levels of CBS in DS brains are approximately three times
      greater than those in the normal individuals. CBS is localized to astrocytes and
      those surrounding senile plaques in the brains of DS patients with AD. The over
      expression of CBS may cause the developmental abnormality in cognition in DS
      children and that may lead to AD in DS adults.

PMID- 16274670
TI  - Human hepatitis B virus X protein induces apoptosis in HepG2 cells: role of BH3
      domain.
AB  - The smallest protein of hepatitis B virus, HBX, has been implicated in the
      development of liver diseases by interfering with normal cellular processes. Its
      role in cell proliferation has been unclear as both pro-apoptotic and anti
      apoptotic activities have been reported. We showed molecular evidence that HBX
      induced apoptosis in HepG2 cells. A Bcl-2 Homology Domain 3 was identified in
      HBX, which interacted with anti-apoptotic but not pro-apoptotic members of the
      Bcl-2 family of proteins. HBX induced apoptosis when transfected into HepG2
      cells, as demonstrated by both flow cytometry and caspase-3 activity. However,
      HBX protein may not be stable in apoptotic cells triggered by its own expression
      as only its mRNA or the fusion protein with the glutathione-S-transferase was
      detected in transfected cells. Our results suggested that HBX behaved as a pro
      apoptotic protein and was able to induce apoptosis.

PMID- 16274671
TI  - Signals of seminal vesicle autoantigen suppresses bovine serum albumin-induced
      capacitation in mouse sperm.
AB  - Capacitation is the prerequisite process for sperm to gain the ability for
      successful fertilization. Unregulated capacitation will cause sperm to undergo a
      spontaneous acrosome reaction and then fail to fertilize an egg. Seminal plasma
      is thought to have the ability to suppress sperm capacitation. However, the
      mechanisms by which seminal proteins suppress capacitation have not been well
      understood. Recently, we demonstrated that a major seminal vesicle secretory
      protein, seminal vesicle autoantigen (SVA), is able to suppress bovine serum
      albumin (BSA)-induced mouse sperm capacitation. To further identify the mechanism
      of SVA action, we determine the molecular events associated with SVA suppression
      of BSA's activity. In this communication, we demonstrate that SVA suppresses the
      BSA-induced increase of intracellular calcium concentration ([Ca2+]i),
      intracellular pH (pH(i)), the cAMP level, PKA activity, protein tyrosine
      phosphorylation, and capacitation in mouse sperm. Besides, we also found that the
      suppression ability of SVA against BSA-induced protein tyrosine phosphorylation
      and capacitation could be reversed by dbcAMP (a cAMP agonist).

PMID- 16274672
TI  - Ciliary neurotrophic factor promotes inactivation of muscle Ca2+ channels via
      PKC.
AB  - The actions of the ciliary neurotrophic factor (CNTF) were assessed on adult
      mouse skeletal muscle L-type Ca2+ currents and on Ca2+ release from sarcoplasmic
      reticulum. Currents were measured with the whole cell patch clamp technique. Ca2+
      signals in response to single action potentials were recorded with Fluo3-AM. CNTF
      (20 ng/ml) reversibly reduced the amplitude of Ca2+ channel currents by 50%
      within 15 min. In addition, CNTF greatly increased the rate of inactivation
      during depolarizing pulses and shifted the steady state inactivation curve by -12
      mV. The effects of CNTF were mimicked by the PKC activator PMA and prevented by
      the PKC-inhibitor chelerythrine. In contrast to the effects on the Ca2+
      conductance, charge movement and Ca2+ signals remained unaffected by CNTF. These
      results suggest that CNTF can rapidly decrease muscle Ca2+ channel currents by
      promoting inactivation, probably through an intracellular PKC-dependent
      mechanism.

PMID- 16274673
TI  - GABAergic disinhibition facilitates polysynaptic excitatory transmission in rat
      anterior cingulate cortex.
AB  - Various studies implicate the anterior cingulate cortex (ACC) in processing pain.
      Combining whole-cell patch clamp recordings in rat ACC slices and a formalin
      induced conditioned place avoidance (F-CPA) behavioral model, the present study
      was to address the effect of GABA(A) receptors on excitatory transmission to ACC
      layer V neurons and its possible functional significance related to pain. Removal
      of GABA(A) inhibition by bicuculline (10 microM) induced a novel long-lasting
      response in layer V neurons, which could be blocked by high divalent
      extracellular solution and was sensitive to relatively higher rate stimuli. Co
      application of NMDA receptor antagonist APV (50 microM) and non-NMDA receptor
      antagonist DNQX (10 microM) completely blocked the responses. Enhancement of
      inhibition by intra-ACC microinjection of muscimol abolished the acquisition of F
      CPA without affecting formalin-induced acute nociceptive responses. These results
      suggest that GABA(A) inhibition may be involved in pain-related aversion by
      modulating glutamate-mediated excitatory transmission in the ACC.

PMID- 16274674
TI  - Effect of nitric oxide on hyperpolarization-activated current in substantia
      gelatinosa neurons of rats.
AB  - Central sensitization is the hyperexcitability of spinal processing after
      peripheral nerve injury or inflammation. This phenomenon may be associated with
      nitric oxide (NO) signal pathway in synapse. Here, we have investigated the
      effect of NO on hyperpolarization-activated inward current (I(h)) in substantia
      gelatinosa (SG) neurons, using the whole-cell patch clamp technique. I(h) was
      increased by the application of sodium nitro prusside (SNP, a NO donor) or 8Br
      cGMP. The stimulatory effects of NO were abolished by guanylyl cyclase inhibitor,
      ODQ, suggesting that the effect of NO was mediated by cGMP. However, this effect
      of NO was not prevented by the pretreatment with KT5823, PKG inhibitor. Taken
      together, the activation of I(h) in SG neurons could be mediated by NO-cGMP
      dependent pathway. These results reveal an involvement of NO in excitability of
      SG neuron via the activation of I(h) may be associated with central
      sensitization.

PMID- 16274675
TI  - Nitric oxide modulates calcium entry through P/Q-type calcium channels and N
      methyl-d-aspartate receptors in rat cortical neurons.
AB  - Voltage-gated calcium channels (VGCC) and N-methyl-d-aspartate receptors (NMDAR)
      account for most of the depolarization-induced neuronal calcium entry. The
      susceptibility of individual routes of calcium entry for nitric oxide (NO) is
      largely unknown. We loaded cultured rat cortical neurons with fluo-4
      acetoxymethylester to study the effect of the NO synthase inhibitor Nomega-nitro
      l-arginine and the NO donor S-nitroso-N-acetylpenicillamine on the intracellular
      calcium concentration ([Ca2+]i). The potassium-induced [Ca2+]i increase was
      amplified by Nomega-nitro-l-arginine and attenuated by S-nitroso-N
      acetylpenicillamine. This modulation was abolished by either the P/Q-type VGCC
      antagonist omega-agatoxin IVA or by the NMDAR antagonist MK-801, but not by N
      type (omega-conotoxin GVIA) or L-type (nimodipine) VGCC blockers. These results
      suggest that NO can modulate neuronal calcium entry during depolarization by
      interacting with P/Q-type VGCC and NMDAR.

PMID- 16274676
TI  - Expression of c-Fos in the mouse Edinger-Westphal nucleus following ethanol
      administration is not secondary to hypothermia or stress.
AB  - Restraint stress, lipopolysaccharide (LPS), and ethanol (EtOH) administration
      have all been found to induce c-Fos in the brain, and to cause hypothermia. The
      present study was designed to assess whether the c-Fos expression that occurs in
      the Edinger-Westphal nucleus (EW) after EtOH administration is independent of the
      hypothermia or any stress effects that occur. To test this, we used restraint
      stress and LPS in addition to EtOH, and also examined two control areas, the
      dorsal raphe nucleus (DRN) and the periaqueductal gray (PAG), in addition to EW.
      Male C57BL6/J mice were used. Groups of mice received intraperitoneal (IP)
      injections of EtOH (2 g/kg), LPS (600 microg/kg or 50 microg/kg), or saline. A
      separate group of mice received no injection, but were placed in plastic
      restrainers for the entirety of the experiment. For all groups, core temperatures
      were monitored rectally every 30 min for 3 h postinjection, after which, the
      animals were sacrificed. Then, the number of Fos-positive cells in the brain
      regions of the EW, DRN, and PAG was quantified. Both EtOH and restraint stress
      induced a transient hypothermia, where core temperature (Tc) declined immediately
      and then rose again. Both doses of LPS induced a slower developing, longer
      lasting hypothermia, while saline had no effect on Tc. Only EtOH induced a
      significant amount of c-Fos in EW, while both doses of LPS and restraint stress
      induced c-Fos in DRN, and only restraint stress caused induction in PAG. These
      data demonstrate that activation of EW after EtOH is unrelated to hypothermia or
      stress.

PMID- 16274677
TI  - Validation of a selective serotonin 5-HT(2C) receptor antibody for utilization in
      fluorescence immunohistochemistry studies.
AB  - Although radioligand binding studies have shown that the serotonin 5-HT(2C)
      receptor (5-HT(2C)R) is widely expressed throughout the brain, more detailed
      knowledge of 5-HT(2C)R distribution within different neuronal populations will
      aid in understanding the mechanisms through which this receptor acts. Double
      label immunohistochemical procedures can be utilized to examine the localization
      of receptors within specific neuronal populations. In order to conduct such
      studies, however, it was first necessary to examine the utility and specificity
      of two commercially available anti-5-HT(2C)R antibodies [from Santa Cruz (SC) and
      BD PharMingen (PH)]. In male Sprague-Dawley rats, both antibodies produced
      widespread immunoreactivity (IR) throughout the brain area chosen for study, the
      ventral tegmental area, which is the origin of the dopamine mesocorticoaccumbens
      "reward" pathway. Co-labeling with the SC and PH 5-HT(2C)R antibodies
      demonstrated that IR for the two antibodies largely overlapped. However, SC 5
      HT(2C)R IR was more concentrated within IR cell bodies and was more consistent
      among assays than the PH 5-HT(2C)R IR. Thus, the SC 5-HT(2C)R antibody was chosen
      for subsequent studies. When examined in 5-HT(2C)R knockout vs. wild-type mice,
      the SC 5-HT(2C)R antibody produced widespread IR in wild-type, but not 5-HT(2C)R
      knockout, mice. In addition, 5-HT(2C)R-IR was not present in either native CHO
      cells, known to be devoid of 5-HT(2A)R or 5-HT(2C)R, or in CHO cells transfected
      with the 5-HT(2A)R. Thus, these studies suggest that the SC 5-HT(2C)R antibody
      produces reliable staining selective for 5-HT(2C)R vs. 5-HT(2A)R in rodent brains
      and is therefore suitable for use in future immunofluorescence 5-HT(2C)R
      localization studies.

PMID- 16274682
TI  - Acceleration of functional reentry by rapid pacing in anisotropic cardiac
      monolayers: formation of multi-wave functional reentries.
AB  - OBJECTIVE: Attempts to cardiovert tachycardia by rapid point pacing can sometimes
      result in transient or stable increase of the heart rate (acceleration), changed
      ECG morphology, and/or fibrillation. The goal of this study was to investigate
      the effect of rapid pacing on the dynamics of functional reentry in monolayer
      cultures of cardiac cells. METHODS: Fully confluent, uniformly anisotropic
      monolayers of neonatal rat ventricular myocytes were prepared using methods of
      microabrasion. Cells were paced by a point electrode at rest and during
      functional reentry, and membrane voltages were optically mapped. RESULTS: Point
      pacing readily induced single loop anisotropic functional reentry with
      monomorphic optical pseudo-ECG (pECG) and average rotation period of 193+/-52 ms
      (n=71 monolayers). Attempts to cardiovert reentry by rapid pacing at rates 10-50%
      faster than the reentry rate were successful in 57/71 monolayers. In 14/71
      monolayers, the number of rotating waves was stably increased by 1 to 4, yielding
      a 10-70% acceleration of pECG rate and change to a different monomorphic or
      polymorphic pECG. The resulting multi-wave functional reentries were classified
      based on the number and direction of their rotating waves. The higher the number
      of waves in the multi-wave reentry, the more accelerated was the rate of cell
      firing in the monolayer. Importantly, stable acceleration was only inducible in
      monolayers with relatively deep and broad conduction velocity restitution
      relationships. Reapplication of point pacing further accelerated, decelerated, or
      eventually terminated the reentrant activity. CONCLUSIONS: These results suggest
      that stable multiplication of rotating waves in conjunction with a deep and broad
      conduction velocity restitution relationship is a possible mechanism for stable
      acceleration of functional reentry by rapid pacing.

PMID- 16274683
TI  - Synaptic remodeling at the skeletal neuromuscular junction of
      acetylcholinesterase knockout mice and its physiological relevance.
AB  - Acute inhibition of synaptic acetylcholinesterase (AChE) is fatal to normal
      animals, but AChE-knockout mice (AChE-/-) expressing normal levels of
      butyrylcholinesterase (BChE) could live to adulthood without AChE expression. The
      present study was undertaken to determine whether compensatory mechanisms occur
      in the mutant that allow an effective neuromuscular transmission in the chronic
      absence of AChE. For this we evaluated neuromuscular transmission and the
      distribution of nicotinic acetylcholine receptors (nAChRs) and motor nerve
      terminals on isolated nerve-muscle preparations from AChE-/- mice. AChE-/-
      hemidiaphragm muscles maintained at 32 degrees C can support muscle twitches, and
      tetanic contractions during intermittent nerve-stimulation over a wide range of
      physiological frequencies, even though they develop less force, than age-matched
      wild-type (AChE+/+) muscles. Tetanic fade in AChE-/- muscles was temperature
      sensitive and more marked at 22 degrees C than at 32 degrees C. Inhibition of
      BChE by tetraisopropylpyrophosphoramide (Iso-OMPA) intensified tetanic fade in
      AChE-/- muscles, but had no effect on AChE+/+ muscles, suggesting that BChE plays
      a protective role in nerve terminals. Skeletal muscles from AChE-/- mice adapted
      to the lack of AChE enzymatic activity by triggering a synaptic remodeling that
      critically occurred between the second and third week of postnatal development,
      during synapse elimination. In AChE-/- muscles nAChRs distributed in a smaller
      and fragmented surface area, that mirrored the branching pattern of motor nerve
      terminals. These findings indicate that the neuromuscular system exhibits a
      remarkable plasticity and adaptive responses to the chronic absence of AChE
      activity that has important consequences for the functioning of the neuromuscular
      junction.

PMID- 16274684
TI  - Mutations of acetylcholinesterase which confer insecticide resistance in insect
      populations.
AB  - Resistance-modified acetylcholinesterases have been described in many insect
      species and sequencing of their genes has allowed several point mutations to be
      described. Most mutations line the active site gorge. Each mutation provides a
      specific resistance pattern: it confers resistance to one insecticide but may
      increase sensitivity to another. Most mutations alter hydrolysis of the substrate
      by decreasing the rate of enzyme deacetylation and by diminishing the stability
      of the enzyme. Mutations are often found in combination in the same protein. This
      has several consequences: it increases the level of resistance, it enlarges the
      spectrum of resistance and it may restore the catalytic efficiency of the enzyme.
      Natural populations are heterogeneous, composed of a mixture of different
      alleles.

PMID- 16274685
TI  - Autoantibodies against oxidized LDL correlate with serum concentrations of
      ceruloplasmin in patients with cardiovascular disease.
AB  - BACKGROUND: Ceruloplasmin (CP) has been suggested to play a role in the oxidative
      modification of LDL. The correlation between autoantibodies against oxidized LDL
      (anti-oxLDL), markers of oxidative stress, and the concentration of CP has not
      been previously investigated. We examined the status of these parameters in
      patients with myocardial infarction (MI) and stable angina. METHODS: Blood
      samples were collected from patients with MI (n=56), stable angina (n=96) and
      from healthy controls (n=109). Levels of CP and copper were determined using
      turbidimetry and atomic absorption spectrophotometry, respectively. Levels of
      anti-oxLDL were obtained by ELISA. RESULTS: Serum concentrations of CP, copper
      and anti-oxLDL were significantly higher in both groups of patients than those in
      controls. Among patient groups, concentrations of CP and copper were not
      significantly different, however, the concentrations of anti-oxLDL were higher in
      MI patients than that in angina (P=0.001), and were greatly influenced by
      underlying conditions such as diabetes mellitus, hypertension and smoking.
      Significant positive correlation was observed between serum concentrations of
      both CP and copper and the concentrations of anti-oxLDL in both patient groups
      but not in controls. CONCLUSIONS: High concentrations of anti-oxLDL suggest an
      increase in oxidative stress that would contribute to disease severity. The
      observed correlation of CP with anti-oxLDL may suggest a possible pro-oxidative
      activity of CP in patients with cardiovascular disease.

PMID- 16274686
TI  - An in vitro study of cryopreserved and fresh human arteries: a comparison with
      ePTFE prostheses and human arteries studied non-invasively in vivo.
AB  - The surgical options in arterial reconstruction are: the use of autologous
      arteries; autologous veins; or expanded polytetrafluoroethylene (ePTFE) grafts.
      However, the development of intimal hyperplasia when using veins or ePTFE grafts
      has been associated with graft failure. Since autologous arteries are not always
      available, the use of cryopreserved arteries has to be considered. The aims of
      this study were: (a) to compare the viscoelastic properties of stored
      cryopreserved arteries and fresh arteries by in vitro analysis; and (b) to
      compare the viscoelastic properties of arteries measured non-invasively in
      normotensive patients, with fresh arteries, cryopreserved arteries, and ePTFE
      segments. The viscoelastic studies were performed in normotensive patients using
      stress-strain analysis with non-invasive measurement of pressure and diameter in
      the common carotid artery, and in vitro measurements of pressure and diameter in
      arteries and prostheses. The in vitro studies showed that the elastic modulus
      (E), viscous modulus (eta), Stiffness Index (SI), Peterson modulus (Ep), and the
      pulse wave velocity (PWV) values for human cryopreserved carotid arteries were
      similar to the values obtained non-invasively in normotensive subjects (P>0.05)
      and to human fresh vessels (P>0.05). In vitro, the SI, Ep, PWV, and E values of
      ePTFE were significantly higher than the observed values in subjects and with
      fresh and cryopreserved arteries (P<0.05); on the other hand the ePTFE eta values
      were the lowest (P<0.05). We concluded that cryopreserved arteries have similar
      viscoelastic properties to those obtained in vivo in the arteries of normotensive
      subjects and in vitro in fresh arteries. Consequently, we conclude that the
      cryopreservation procedure does not modify the mechanical properties of the
      arterial wall.

PMID- 16274687
TI  - Increased serum estrogenic bioactivity in three male newborns with ambiguous
      genitalia: a potential consequence of prenatal exposure to environmental
      endocrine disruptors.
AB  - In the past 15 years, anomalies of male sexual differentiation have greatly
      increased in both wildlife and humans in different parts of the world.
      Environmental endocrine disruptors have been implicated in the dramatic rise in
      neonatal ambiguous genitalia with variable rates of severity, such as micropenis,
      cryptorchidism, and isolated or associated hypospadias. Because most
      environmental pollutants, such as organochlorine pesticides, polychlorinated
      biphenyls, dioxins and furans, alkylphenol polyetholyethoxylates, and
      phytoestrogens and phtalates, have estrogenic and antiandrogenic activity, they
      are able to interfere with normal fetal male sexual differentiation. In a
      neonatal screening program of ambiguous genitalia, we had the opportunity to
      evaluate three newborns with male pseudohermaphroditism (MPH) whose mothers were
      exposed to endocrine disruptors during pregnancy. All had normal testosterone
      production after human chorionic gonadotrophin stimulation testing, suggesting
      androgen resistance or so-called idiopathic MPH. Sequences of the 5alpha
      reductase and androgen receptor genes were normal. Since environmental pollutants
      are known for their estrogenic activity and can be released progressively from
      the adipose tissue where they accumulate, we detected their presence by measuring
      the estrogenic bioactivity of the newborns' serum with a recently developed
      ultrasensitive bioassay. We found higher estrogenic bioactivity in these newborns
      than in controls. In conclusion, the maternal exposure to environmental
      pollutants during pregnancy and high estrogenic bioactivity in the newborns'
      serum highly suggest that ambiguous genitalia are related to fetal exposure to
      endocrine disruptors.

PMID- 16274688
TI  - Phosphorylation of ezrin enhances microvillus length via a p38 MAP-kinase pathway
      in an immortalized mouse hepatic cell line.
AB  - The apical microvilli are closely related with the development and the
      maintenance of cell polarization, and the length of microvilli varies in a
      regular way among cell types. Ezrin, a member of the ezrin/radixin/moesin (ERM)
      family, seems to be involved in the formation and stabilization of the apical
      microvilli. We found that phosphorylation of ezrin caused elongation of
      microvilli via a p38 MAP-kinase signaling pathway in an immortalized mouse
      hepatic cell line. When, in the oncogenic Raf-1-transfected mouse hepatic cell
      line, epithelial to mesenchymal transition (EMT) indicated as down-regulation of
      E-cadherin and up-regulation of Snail occurred, loss of microvilli and down
      regulation of ezrin but not radixin and moesin were also observed. In the Raf-1
      transfectants treated with the MAP-kinase inhibitor PD98059 and the p38 MAP
      kinase inhibitor SB203580, the numbers of microvilli and the expression of ezrin,
      E-cadherin and Snail were recovered. More interestingly, treatment with SB203580
      induced elongation of microvilli and increased phosphorylation of ezrin (at Thr
      567 and Tyr-353). Phosphorylated ezrin-positive dots were colocalized with actin
      positive dots on the surface of some Raf-1 transfectants treated with SB203580.
      These results suggested that phosphorylation of ezrin via the p38 MAP-kinase
      signaling pathway might be involved in the formation of microvilli during
      development of epithelial cell polarization.

PMID- 16274689
TI  - Trichinella spiralis: macrophage activity and antibody response in chronic murine
      infection.
AB  - The role of macrophages, their products, and the specific antibody response were
      examined during chronic Trichinella spiralis infection in BALB/c mice. Adult T.
      spiralis in intestines were detected from 5 to 20 dpi. Muscle larvae numbers
      peaked at 45 dpi and thereafter a reduction was noted. The highest numbers of
      macrophages in the peritoneal cavity of infected mice were obtained up to 30 dpi.
      The production of NO by macrophages in infected mice was suppressed at 5 dpi, and
      then NO release increased until 45 dpi. The levels of NO in plasma and urine were
      lower in infected mice during the entire experiment in comparison to control. The
      production of O(2)(-) in peritoneal macrophages was inhibited during the first
      two weeks after infection and then increased until 90 dpi. Circulating T.
      spiralis antigens in plasma and urine were detected from 5 to 30 dpi. Specific
      IgM and IgA in serum increased until 20 dpi. IgG, IgG(1), and IgG(2) levels in
      serum increased until 60 dpi.

PMID- 16274690
TI  - Leishmania major and Leishmania tropica: II. Effect of an immunomodulator, S(2)
      complex on the enzymes of the parasites.
AB  - S(2) complex has been reported to have a direct antileishmanial effect. The
      possibility that the direct antileishmanial effect may be due to inhibition of
      key enzymes involved in glucose metabolism and/ or enzymes associated with
      virulence was investigated. Cell pellets were prepared from cultures of both
      axenic amastigotes and promastigotes of Leishmania major (MHOM/IQ/93/MRC6) and L.
      tropica (MHOM/IQ/93/MRC2). S(2) complex, at various concentrations, was added to
      the enzyme extracts prepared from the pellets. Results show that in the Embden
      Meyerhof pathway, both hexokinase and glucose-phosphate isomerase but not
      fructophosphokinase were dose dependently inhibited. In the hexose-monophosphate
      shunt both glucose-6-phosphate dehydrogenase and ribose-5-phosphate isomerase
      were dose dependently inhibited. Malic dehydrogenase and malic enzyme from the
      citric-acid cycle were both dose dependently inhibited but succinate
      dehydrogenase from the same pathway was not inhibited. Both enzymes associated
      with virulence (protease and acid phosphatase), showed activation rather than
      inhibition at higher doses of S(2) complex. Thus, the direct antileishmanial
      effect of S(2) complex may result, partially or entirely, from the inhibition of
      enzymes that are necessary for the parasites' carbohydrate metabolism.

PMID- 16274691
TI  - The human placental derived BeWo cell line: a useful model for selecting
      Plasmodium falciparum CSA-binding parasites.
AB  - Chondroitin sulfate A (CSA) present in the placental intervillous blood spaces
      has been described as the main receptor involved in the massive sequestration of
      Plasmodium falciparum parasitized erythrocytes to the placenta. Placental
      parasite isolates are functionally distinct from isolates that sequester in other
      organs, because they do not cytoadhere to CD36 but instead bind to CSA. To
      investigate for the parasites molecules associated with the CSA adhesion
      phenotype, different methodologies have been developed to select for CSA-binding
      lines in vitro mainly using non-placental sources of CSA that differ in their
      sulfation pattern. In this study, we show that the human trophoblastic BeWo cell
      line is a very efficient alternative to select for the CSA-binding phenotype in
      parasitized erythrocytes.

PMID- 16274692
TI  - Salivary cortisol changes in humans after winning or losing a dominance contest
      depend on implicit power motivation.
AB  - In two studies, one with an all-male German sample and the other with a mixed-sex
      U.S. sample, subjects competed in pairs on reaction time-based cognitive tasks.
      Participants were not aware that contest outcome was experimentally varied. In
      both studies, implicit power motivation, defined as the non-conscious need to
      dominate or have impact on others, predicted changes in salivary cortisol from
      before to after the contest. Increased cortisol post-contest was associated with
      high levels of power motivation among losers but with low levels of power
      motivation among winners, suggesting that a dominance success is stressful for
      low-power individuals, whereas a social defeat is stressful for high-power
      individuals. These results emerged only in participants tested in the afternoon,
      possibly because of greater variability in cortisol in the morning due to the
      rapid decline after the morning peak. These studies add to the evidence that
      individual differences greatly influence whether a social stressor like losing a
      contest activates the HPA axis in humans.

PMID- 16274693
TI  - Crystal structure of a novel tetrameric complex of agonist-bound ligand-binding
      domain of Biomphalaria glabrata retinoid X receptor.
AB  - Nuclear receptors form an important class of transcription regulators in
      metazoans. To learn more about the evolution of these proteins, we have initiated
      structural studies on nuclear receptor ligand-binding domains from various
      animals. Here we present the crystal structure of the ligand-binding domain (LBD)
      of the retinoid X receptor (RXR) from the mollusc Biomphalaria glabrata. The
      structure reveals a novel tetrameric association in which each monomer is
      complexed to the human RXR ligand 9-cis retinoic acid and to a human co-activator
      derived peptide. The ligand and the co-activator peptide are bound in essentially
      the same manner as observed in previously reported human RXR LBD structures,
      suggesting that the mechanisms of RXR-mediated transcription regulation are very
      similar in mollusc and human. The structure shows further that binding of ligand
      and co-activator peptide does not necessarily lead to the typical holo
      conformation in which helix 12 (H12) folds back and packs against the LBD. Within
      a canonical dimer, only one monomer is in this closed agonist conformation. The
      other monomer is in an open conformation with H12 protruding from the LBD core,
      occupying the H12 interaction groove of another open monomer in an adjacent dimer
      in a domain swapping fashion, thus resulting in a tetrameric association.
      Additional tetramer interfaces are formed between H11 of the closed LBD and H6 of
      the open LBD. This novel holo-tetramer configuration may have a biological role
      in activating genes whose promoters are poorly recognised by dimers but much more
      efficiently by the corresponding tetramers.

PMID- 16274694
TI  - A technique to detect and to quantify fasciocutaneous blood vessels in small
      laboratory animals ex vivo.
AB  - PURPOSE: A microangiographical technique is described, which allows visualization
      of small and capillary blood vessels and quantification of fasciocutaneous blood
      vessels by means of digital computer analysis in very small laboratory animals.
      MATERIALS AND METHODS: The left carotid artery of 20 nu/nu mice was cannulated
      (26 gauge) and a mixture of gelatin, bariumsulfate, and green ink was injected
      according to standardized protocol. Fasciocutaneous blood vessels were visualized
      by digital mammography and analyzed for vessel length and vessel surface area as
      standardized units [SU] by computer program. RESULTS: With the described
      microangiography method, fasciocutaneous blood vessels down to capillary size
      level can be clearly visualized. Regions of interest (ROIs) can be defined and
      the containing vascular network quantified. Comparable results may be obtained by
      calculating the microvascular area index (MAI) and the microvascular length index
      (MLI), related to the ROIs size. Identical ROIs showed a high reproducibility for
      measured [SU] < 0.01 +/- 0.0012%. CONCLUSION: Combining microsurgical techniques,
      pharmacological knowledge, and modern digital image technology, we were able to
      visualize small and capillary blood vessels even in small laboratory animals. By
      using our own computer analytical program, quantification of vessels was
      reliable, highly reproducible, and fast.

PMID- 16274695
TI  - Virtual reality simulators in orthopedic surgery: what do the surgeons think?
AB  - BACKGROUND: There is increasing pressure to develop virtual reality surgical
      simulation that can be used in surgical training. However, little is known of the
      attitudes of the surgical community toward such simulation, and which aspects of
      simulation are most important. MATERIALS AND METHODS: A postal survey on
      attitudes to surgical simulation was sent to all New Zealand orthopedic surgeons
      and advanced trainees. This comprised of 44 questions in 10 sections, using
      either a visual analogue scale (0 to 10) or free text box replies. Results were
      analyzed for two sub-groups; surgeons qualified before 1990 and those qualified
      in or after 1990 or still in training. RESULTS: Of the 208 possible responses,
      142 were received, a response rate of 68%. Only four respondents had tried a
      surgical based simulator. Earlier qualified surgeons were more likely to agree
      that simulation was an effective way to practice surgical procedures, median
      score 7.7 versus 5.6 (P = 0.03). Both groups thought the most important task for
      simulation was practicing angulation/spatial orientation (median score 8.4/10),
      while a realistic view of the operation was the most important requirement
      (median score 9/10). Both groups were unconvinced that simulation would impact on
      their practice in the next 5 years, with this statement being scored lower by
      later qualified surgeons, median score 2.4 versus 4.1 (P = 0.04). CONCLUSIONS:
      Orthopedic surgeons in New Zealand are supportive of surgical simulation but do
      not expect simulation to have an impact in the near future. Intriguingly, later
      qualified surgeons and trainees are more skeptical than their earlier qualified
      colleagues.

PMID- 16274696
TI  - Beyond the epithelial mucosa barrier: monitoring of microvascular perfusion
      dysfunction in critically endangered intestinal transplants(1,2).

PMID- 16274697
TI  - ANCA-associated vasculitis (AAV) causing bilateral cerebral infarction and
      subsequent intracerebral hemorrhage without renal and respiratory dysfunction.
AB  - A 56-year-old man complained of headache and the analgesia of the four
      extremities. Laboratory data presented signs of inflammation, but no other
      abnormality such as renal or respiratory dysfunction. Two months after the
      appearance of the primary symptoms, he developed cerebral infarction of the
      bilateral corona radiata. The patient did not have any of the risk factors for
      cerebrovascular disease. He was diagnosed with anti-neutrophil cytoplasmic
      autoantibody (ANCA)-associated vasculitis (AAV) because the systemic examinations
      revealed only that he tested positive for anti-neutrophil cytoplasmic
      autoantibody (ANCA). Moreover, the biopsy of the sural nerve displayed
      microscopic polyangitis (MPA). Despite undergoing steroid pulse therapy, the
      patient died from the fatal cerebral hemorrhage. The clinical course of AAV is
      rapid progressive. In cases of atypical cerebrovascular disease, the possibility
      of ANCA should be investigated.

PMID- 16274698
TI  - The smallest of all worlds: pollination networks.
AB  - A pollination network may be either 2-mode, describing trophic and reproductive
      interactions between communities of flowering plants and pollinator species
      within a well-defined habitat, or 1-mode, describing interactions between either
      plants or pollinators. In a 1-mode pollinator network, two pollinator species are
      linked to each other if they both visit the same plant species, and vice versa
      for plants. Properties of 2-mode networks and their derived 1-mode networks are
      highly correlated and so are properties of 1-mode pollinator and 1-mode plant
      networks. Most network properties are scale-dependent, i.e. they are dependent
      upon network size. Pollination networks have the strongest small-world properties
      of any networks yet studied, i.e. all species are close to each other (short
      average path length) and species are highly clustered. Species in pollination
      networks are much more densely linked than species in traditional food webs, i.e.
      they have a higher density of links, a shorter distance between species, and
      species are more clustered.

PMID- 16274699
TI  - Predicting rRNA-, RNA-, and DNA-binding proteins from primary structure with
      support vector machines.
AB  - In the post-genome era, the prediction of protein function is one of the most
      demanding tasks in the study of bioinformatics. Machine learning methods, such as
      the support vector machines (SVMs), greatly help to improve the classification of
      protein function. In this work, we integrated SVMs, protein sequence amino acid
      composition, and associated physicochemical properties into the study of nucleic
      acid-binding proteins prediction. We developed the binary classifications for
      rRNA-, RNA-, DNA-binding proteins that play an important role in the control of
      many cell processes. Each SVM predicts whether a protein belongs to rRNA-, RNA-,
      or DNA-binding protein class. Self-consistency and jackknife tests were performed
      on the protein data sets in which the sequences identity was < 25%. Test results
      show that the accuracies of rRNA-, RNA-, DNA-binding SVMs predictions are
      approximately 84%, approximately 78%, approximately 72%, respectively. The
      predictions were also performed on the ambiguous and negative data set. The
      results demonstrate that the predicted scores of proteins in the ambiguous data
      set by RNA- and DNA-binding SVM models were distributed around zero, while most
      proteins in the negative data set were predicted as negative scores by all three
      SVMs. The score distributions agree well with the prior knowledge of those
      proteins and show the effectiveness of sequence associated physicochemical
      properties in the protein function prediction. The software is available from the
      author upon request.

PMID- 16274700
TI  - Novel approaches to plant drug discovery based on high throughput pharmacological
      screening and genetic manipulation.
AB  - Plants are potentially important for novel therapeutic drug leads, but the
      slowness of conventional methods for investigation of plants limits enthusiasm in
      the pharmaceutical industry. To overcome some of the drawbacks, we have applied
      high throughput pharmacological screening (HTPS) to crude plant extracts. Using a
      "differential smart screen", (DSS) the spectrum of activity contained in a crude
      extract is measured at several closely related receptor subtypes. This spectrum
      is then compared to that of known compounds. A unique spectrum suggests that the
      extract merits further investigation. Evaluation of species and environmental
      libraries of whole plants has demonstrated the value of this approach for rapid
      prioritization of plants for investigation. In addition, genomic and genetic
      manipulation of plants and plant cell cultures can increase the value of DSS. For
      example, the whole genomic potential of a plant species for biodiversity can be
      accessed by using gain of function mutations to generate a "functional genomics
      library" of mutant clonal cultures, and the bioactivity of these cultures tested
      by DSS. Clones that overproduce activity differing from the wild-type plant can
      be identified in this way. This "Natural Products Genomics" (NPG) strategy is
      limited by the massive numbers of clonal cultures that are required to cover all
      possible gain-of-function mutations. The rapidity and efficiency of this process
      can be improved by using transgenic plants expressing appropriate mammalian
      proteins. These may be designed to make the plant cell resemble a human cell for
      a specific form of toxicity. Now, "unnatural selection" of resistant mutant
      clones can be used to provide a sub-population potentially enriched in useful
      compounds. Alternatively, transgenic plant cells can be used for "in situ
      screening" in which a mammalian receptor protein, linked to a reporter construct,
      such as green fluorescent protein, is expressed. Clonal cultures that produce
      ligands for this receptor can now be rapidly identified visually in an ultra
      HTPS. Overall, our aim is to use pharmacological screening, together with
      functional genomic approaches, to make plant drug discovery competitive with
      combinatorial chemistry.

PMID- 16274701
TI  - Casein kinase Iepsilon down-regulates phospho-Akt via PTEN, following genotoxic
      stress-induced apoptosis in hematopoietic cells.
AB  - Here, we show a functional role of casein kinase I (CKI) epsilon in hematopoietic
      cell survival through the modification of phosphatidylinositol 3-kinase
      (PI3K)/Akt signaling. Introduction of wild-type (WT)-CKIepsilon into interleukin
      3 (IL-3)-dependent 32D cells increased the sensitivity to genotoxic stresses,
      such as gamma-irradiation, etoposide, and IL-3 deprivation, whereas kinase
      negative (KN)-CKIepsilon suppressed it. Contrary to KN-CKIepsilon, WT-CKIepsilon
      attenuated the IL-3-induced activation of Akt with the increase of PTEN activity.
      Similarly, the increase of Akt activation, as well as PTEN inactivation, was
      accompanied both by a decrease of CKIepsilon expression induced by all-trans
      retinoic acid and by the addition of a specific inhibitor for CKIepsilon in HL-60
      cells. CKIepsilon seems to activate PTEN by physical interaction. These results
      suggest that the CKIepsilon-induced down-regulation of PI3K/Akt signaling through
      PTEN lead to amplified sensitivity to apoptosis. Thus, the suppression of
      CKIepsilon in many human leukemia cell lines may play a role in the cell
      immortalization.

PMID- 16274702
TI  - Comparative screening of plant essential oils: phenylpropanoid moiety as basic
      core for antiplatelet activity.
AB  - Essential oils extracted from different plants (Anthemis nobilis L., Artemisia
      dracunculus L., Cannabis sativa L., Cupressus sempervirens L., Cymbopogon
      citratus (DC.) Stapf., Curcuma longa L., Foeniculum vulgare L., Hypericum
      perforatum L., Hyssopus officinalis L., Mentha spicata L., Monarda didyma L.,
      Ocimum basilicum L., Ocotea quixos Kosterm., Origanum vulgare L., Pinus nigra
      J.F. Arnold, Pinus silvestris L., Piper crassinervium Kunth., Rosmarinus
      officinalis L., Salvia officinalis L., Salvia sclarea L., Santolina
      chamaecyparissus L., Thymus vulgaris L., Zingiber officinaie L.) were screened in
      guinea pig and rat plasma in order to assess antiplatelet activity and inhibition
      of clot retraction. The oils were chemically analysed and a relationship between
      components and ability to affect hemostasis was evidenced. O. quixos, F.
      vulgaris, and A. dracunculus showed the highest antiplatelet activity against
      ADP, Arachidonic Acid and the Thromboxane A2 agonist U46619 (IC50, 4-132 microg
      ml(-1)), and a good ability to destabilize clot retraction (IC50, 19-180 microg
      ml(-1)). For these oils a significant correlation between antiplatelet potency
      and phenylpropanoids content (54-86%) was evidenced thus suggesting a key role
      for this moiety in the prevention of clot formation. These findings provide the
      rationale to take in account the antiplatelet activity in the pharmacological
      screening of natural products containing phenylpropanoids.

PMID- 16274703
TI  - Dominant-negative Rac1 suppresses Ras-induced apoptosis possibly through
      activation of NFkappaB in Ha-ras oncogene-transformed NIH/3T3 cells.
AB  - We investigated the involvement of Rac1 in Ha-ras-overexpression-induced
      apoptosis using a murine NIH/3T3-derived cell line (designated 7-4), which
      contains an inducible Ha-ras oncogene under the regulation of Escherichia coli
      lac operator-repressor system. Ha-ras overexpression was induced by isopropyl
      beta-D-thiogalactoside (IPTG). To reveal the role of endogenous Rac1, the
      dominant negative Rac1(Asn17) gene was transfected into the 7-4 cells. Using two
      cell lines 7-4 Racd2 and 7-4 Racd3 (7-4 derivates) stably expressing Rac1(Asn17),
      we demonstrate that suppression of Rac1 activity blocked Ha-ras-overexpression
      induced apoptosis under a serum-depleted condition, indicating that Rac1 activity
      is required for a Ras-mediated apoptosis pathway. Cell-cycle analysis revealed
      that dominant-negative Rac1 partially shifted cell population from S-phase to
      G0/G1 phase in the cells overexpressing Ha-ras. In contrast to other reports, we
      showed activation of the transcription factor NFkappaB in the two cell lines
      expressing dominant-negative Rac1. All together, our results demonstrate that Ha
      ras-overexpression- induced apoptosis can be blocked by dominant-negative Rac1,
      possibly through decreased S-phase accumulation and increased NFkappaB activity.

PMID- 16274704
TI  - The "So What?" factor.

PMID- 16274705
TI  - Spatial and temporal distribution of dissolved/dispersed aromatic hydrocarbons in
      seawater in the area affected by the Prestige oil spill.
AB  - Seawater samples collected at three depths from 68 stations along the Northern
      Spanish coast were analysed for dissolved/dispersed petroleum aromatic
      hydrocarbons by UV-fluorescence and for 25 individual compounds by GC-MS.
      Sampling was performed in December 2002, just after the Prestige oil spill, and
      in February-March and September 2003. Higher concentrations of total aromatic
      hydrocarbons were found at all depths in the samples collected during December
      2002 off the Galicia coast, with levels ranging between 0.19 and 28.8 microg/L
      eq. oil (0.1-4.8 microg/L chrysene eq.). These values decreased in the following
      cruises, till <0.05-2.86 microg/L oil eq. (av. 0.23 microg/L chrysene eq.) in
      September 2003, possibly representing the background levels for the region.
      However, in the Cantabrian coast they were still high at the surface in the March
      cruise, probably by the late arrival of the fuel-oil to this area. Some coastal
      hot spots were also identified, with values up to 29.2 microg/L fuel-oil eq.,
      close to river mouths and urban areas. The individual PAH distributions in the
      December 2002 sampling off-Galicia were dominated by alkyl-naphthalene
      derivatives, consistently with the pattern distribution shown by the fuel-oil
      water accommodated fraction. The higher concentrations were found in the
      subsurface samples along the Costa da Morte, the area most heavily affected by
      the spill (av. 0.46 microg/L Sigma16 PAHs). The rest of the samples collected in
      other areas exhibited lower concentrations and a more even distribution of 2-4
      ring PAHs, that ranged from 0.09 to 0.37 microg/L (av. 0.15 microg/L Sigma16
      PAHs), with decreasing trends offshore and downward the water column. In
      September 2003, the values were rather uniform, averaging 0.09 microg/L (Sigma16
      PAHs).

PMID- 16274706
TI  - Approximate reduction of multiregional models with environmental stochasticity.
AB  - In this work we extend previous results regarding the use of approximate
      aggregation techniques to simplify the study of discrete time models for
      populations that live in an environment that changes randomly with time.
      Approximate aggregation techniques allow one to transform a complex system
      involving many coupled variables and in which there are processes with different
      time scales, by a simpler reduced model with a fewer number of 'global'
      variables, in such a way that the dynamics of the former can be approximated by
      that of the latter. We present the reduction of a stochastic multiregional model
      in which the population, structured by age and spatial location, lives in a
      random environment and in which migration is fast with respect to demography.
      However, the technique works in much more general settings as, for example, those
      of stage-structured populations living in a multipatch environment. By
      manipulating the original system and appropriately defining the global variables
      we obtain a simpler system. The paper concentrates on establishing relationships
      between the original and the reduced systems for a given separation of time
      scales between the two processes. In particular, we relate the original state
      variables and the global variables and, in the case the pattern of temporal
      variation is Markovian, we relate the presence of strong stochastic ergodicity
      for the original and reduced systems. Moreover, we relate different measures of
      asymptotic population growth for these systems.

PMID- 16274707
TI  - Development of enzymatic probes of oxidative and nitrosative DNA damage caused by
      reactive nitrogen species.
AB  - Chronic inflammation is associated with a variety of human diseases, including
      cancer, with one possible mechanistic link involving over-production of nitric
      oxide (NO*) by activated macrophages. Subsequent reaction of NO* with superoxide
      in the presence of carbon dioxide yields nitrosoperoxycarbonate (ONOOCO2-), a
      strong oxidant that reacts with guanine in DNA to form a variety of oxidation and
      nitration products, such 2'-deoxy-8-oxoguanosine. Alternatively, the reaction of
      NO and O2 leads to the formation of N2O3, a nitrosating agent that causes
      nucleobase deamination to form 2'-deoxyxanthosine (dX) and 2'-deoxyoxanosine (dO)
      from dG; 2'-deoxyinosine (dI) from dA; and 2'-deoxyuridine (dU) from dC, in
      addition to abasic sites and dG-dG cross-links. The presence of both ONOOCO2- and
      N2O3 at sites of inflammation necessitates definition of the relative roles of
      oxidative and nitrosative DNA damage in the genetic toxicology of inflammation.
      To this end, we sought to develop enzymatic probes for oxidative and nitrosative
      DNA lesions as a means to quantify the two types of DNA damage in in vitro DNA
      damage assays, such as the comet assay and as a means to differentially map the
      lesions in genomic DNA by the technique of ligation-mediated PCR. On the basis of
      fragmentary reports in the literature, we first systematically assessed the
      recognition of dX and dI by a battery of DNA repair enzymes. Members of the
      alkylpurine DNA glycosylase family (E. coli AlkA, murine Aag, and human MPG) all
      showed repair activity with dX (k(cat)/Km 29 x 10(-6), 21 x 10(-6), and 7.8 x 10(
      6) nM(-1) min(-1), respectively), though the activity was considerably lower than
      that of EndoV (8 x 10(-3) nM(-1) min(-1)). Based on these results and other
      published studies, we focused the development of enzymatic probes on two groups
      of enzymes, one with activity against oxidative damage (formamidopyrimidine-DNA
      glycosylase (Fpg); endonuclease III (EndoIII)) and the other with activity
      against nucleobase deamination products (uracil DNA glycosylase (Udg); AlkA).
      These combinations were assessed for recognition of DNA damage caused by N2O3
      (generated with a NO*/O2 delivery system) or ONOOCO2- using a plasmid nicking
      assay and by LC-MS analysis. Collectively, the results indicate that a
      combination of AlkA and Udg react selectively with DNA containing only
      nitrosative damage, while Fpg and EndoIII react selectively with DNA containing
      oxidative base lesions caused by ONOOCO2-. The results suggest that these enzyme
      combinations can be used as probes to define the location and quantity of the
      oxidative and nitrosative DNA lesions produced by chemical mediators of
      inflammation in systems, such as the comet assay, ligation-mediated polymerase
      chain reaction, and other assays of DNA damage and repair.

PMID- 16274708
TI  - Induction of UGT1A6 isoform by inflammatory conditions in rat astrocytes.
AB  - Alteration of drug metabolism under diseased conditions is of clinical
      importance. We have investigated the effects of inflammatory conditions on phase
      II drug-metabolizing enzyme activity in rat cultured astrocytes.
      Lipopolysaccharide (LPS) treatment was used to promote inflammatory conditions.
      Thus, we reported that LPS initiates an inflammatory response, which is mediated
      by pro-inflammatory mediators and free radical generation. An increase in
      astrocyte glucuronidation activity was observed after a 48-h LPS treatment. This
      increase in glucuronidation activity was associated with an up-regulation of the
      UGT1A6 isoform mRNA level as shown by RT-PCR and gene reporter assay. Moreover,
      this endotoxin-induced increase in UGT1A6 expression level was blocked by
      actinomycin D and cycloheximide, indicating the requirement for RNA and protein
      synthesis. The UGT1A6 expression enhancement could be prevented by anti
      inflammatory drugs (dexamethasone and NS398) or nitric oxide synthase inhibitors
      (L-NAME and L-NMMA). Moreover, gel shift assay revealed increased activator
      protein-1 (AP-1) binding activity after LPS treatment. We propose, based on the
      data presented, that the action of LPS to induce UGT1A6 isoform up-regulation may
      be mediated by pro-inflammatory mediator accumulation, and AP-1 binding activity
      increase.

PMID- 16274709
TI  - Involvement of GABA(B) receptors of the dorsal hippocampus on the acquisition and
      expression of morphine-induced place preference in rats.
AB  - In the present study, effects of intra-hippocampal CA1 (intra-CA1) injections of
      GABA(B) receptor agonist and antagonist on the acquisition and expression of
      morphine-induced place preference in male Wistar rats have been investigated.
      Subcutaneous administration of different doses of morphine sulphate (0.5-6 mg/kg)
      produced a dose-dependent conditioned place preference (CPP). Using a 3-day
      schedule of conditioning, it was found that the GABA(B) receptor agonist,
      baclofen (0.5-2 microg/rat; intra-CA1), or the GABA(B) receptor antagonist,
      phaclofen (1-3 microg/rat; intra-CA1), did not produce a significant place
      preference or place aversion. Intra-CA1 administration of baclofen (1 and 2
      microg/rat; intra-CA1) decreased the acquisition of CPP induced by morphine (3
      mg/kg; s.c.). On the other hand, intra-CA1 injection of phaclofen (1 and 2
      microg/rat; intra-CA1) in combination with a lower dose of morphine (1 mg/kg)
      elicited a significant CPP. The response of baclofen (2 microg/rat; intra-CA1)
      was reversed by phaclofen (4 and 6 microg/rat; intra-CA1). Furthermore, intra-CA1
      administration of baclofen but not phaclofen before testing significantly
      decreased the expression of morphine (3 mg/kg; s.c.)-induced place preference.
      Baclofen or phaclofen injections had no effects on locomotor activity on the
      testing sessions. It is concluded that the GABA(B) receptors in dorsal
      hippocampus may play an active role in morphine reward.

PMID- 16274710
TI  - Flavonoids, including an unusual flavonoid-Mg2+ salt, from roots of Cudrania
      cochinchinensis.
AB  - Four flavonoids with 2',4'-di-oxygenated B-rings, cochinchinol A (1),
      cochinchinol B (2), (2R,3R)-4',7-dihydroxy-2',5-dimethoxydihydroflavonol (3),
      4',7-dihydroxy-2',5-dimethoxyflavonol (4), along with 11 known compounds, were
      isolated from an ethanolic extract of the roots of Cudrania cochinchinensis.
      Their structures were elucidated by chemical and spectroscopic methods.
      Cochinchinol A (1) and cochinchinol B (2) have two hitherto unprecedented
      flavonol salt structures in natural product chemistry. Cytotoxic activities were
      evaluated against several different cell lines.

PMID- 16274711
TI  - Changes in flux pattern of the central carbohydrate metabolism during kernel
      development in maize.
AB  - Developing kernels of the inbred maize line W22 were grown in sterile culture and
      supplied with a mixture of [U-13C6]glucose and unlabeled glucose during three
      consecutive intervals (11-18, 18-25, or 25-32 days after pollination) within the
      linear phase of starch formation. At the end of each labeling period, glucose was
      prepared from starch and analyzed by 13C isotope ratio mass spectrometry and high
      resolution (13)C NMR spectroscopy. The abundances of individual glucose
      isotopologs were calculated by computational deconvolution of the NMR data. [1,2
      (13)C2]-, [5,6-(13)C2]-, [2,3-(13)C2]-, [4,5-(13)C2]-, [1,2,3-(13)C3]-, [4,5,6
      (13)C3]-, [3,4,5,6-(13)C4]-, and [U-(13)C6]-isotopologs were detected as the
      major multiple-labeled glucose species, albeit at different normalized abundances
      in the three intervals. Relative flux contributions by five different pathways in
      the primary carbohydrate metabolism were determined by computational simulation
      of the isotopolog space of glucose. The relative fractions of some of these
      processes in the overall glucose cycling changed significantly during maize
      kernel development. The simulation showed that cycling via the non-oxidative
      pentose phosphate pathway was lowest during the middle interval of the
      experiment. The observed flux pattern could by explained by a low demand for
      amino acid precursors recruited from the pentose phosphate pathway during the
      middle interval of kernel development.

PMID- 16274712
TI  - The herbal tea approach for artemisinin as a therapy for malaria?

PMID- 16274713
TI  - Heat therapy for cutaneous leishmaniasis elicits a systemic cytokine response
      similar to that of antimonial (Glucantime) therapy.
AB  - Controlled heat delivered as radio waves has been used successfully in the
      treatment of cutaneous leishmaniasis (CL). Here we investigated whether local
      heat therapy has systemic effects, as measured by the modulation of cytokine
      production following heat therapy of CL lesions compared with antimonial
      (Glucantime) treatment. Patients with CL were randomly assigned into this study.
      Heat (50 degrees C for 30s) was applied once. The control group received
      Glucantime therapy for 20 d. Cytokine production by peripheral blood mononuclear
      cells was assayed on days 0, 14 and 28 after onset of treatment. At the end of 28
      d, 75% of lesions were healing or healed in the heat therapy group and 90% in the
      control group (P=0.1261). There was a decrease in IFN-gamma, IL-5 and TNF-alpha
      levels comparing day 0 with day 28 in both groups, but no difference between the
      two therapy groups. In patients with only one of several lesions treated with
      heat therapy, the untreated lesions also healed. Local heat therapy in CL lesions
      leads to systemic cytokine responses similar to that induced by systemic
      Glucantime therapy.

PMID- 16274714
TI  - Entamoeba histolytica and Entamoeba dispar: comparison of two PCR assays for
      diagnosis in a non-endemic setting.
AB  - Detection of Entamoeba histolytica, the causative agent of amoebiasis, is an
      important goal of the clinical parasitology laboratory. The identification of
      Entamoeba dispar as a morphologically identical but non-pathogenic species has
      highlighted the need for non-microscopic detection methods able to differentiate
      between the two organisms. In this study we evaluated the utility of conventional
      PCR and real-time PCR as methods for identification and differentiation of E.
      histolytica and E. dispar. The second aim of this study was to determine the
      relative proportions of infections caused by E. histolytica and the non
      pathogenic E. dispar, allowing a picture of the epidemiological situation in a
      non-endemic setting to be obtained. One hundred and sixty-six clinical samples
      (faecal and liver abscess samples and one intestinal biopsy) belonging to 108
      patients were analysed. More patients with E. dispar infection (8.3%) than
      patients with E. histolytica infection (5.6%) were found by both PCR assays. It
      is concluded that routine diagnosis of invasive amoebiasis performed by a
      combination of microscopy, culture and serology should be complemented with a PCR
      assay such as real-time PCR that offers a practical and clinically acceptable
      alternative for rapid and accurate diagnosis of amoebic infection in patients
      presenting with symptoms indicative of this disease.

PMID- 16274715
TI  - The double burden of communicable and non-communicable diseases in developing
      countries.
AB  - Now, at the dawn of the third millennium, non-communicable diseases are sweeping
      the entire globe. There is an increasing trend in developing countries, where the
      demographic and socio-economic transition imposes more constraints on dealing
      with the double burden of infectious and non-infectious diseases in a poor
      environment, characterized by ill-health systems. It is predicted that, by 2020,
      non-communicable diseases will cause seven out of every ten deaths in developing
      countries. Among non-communicable diseases, special attention is devoted to
      cardiovascular disease, diabetes, cancer and chronic pulmonary disease. The
      burden of these conditions affects countries worldwide but with a growing trend
      in developing countries. Preventative strategies must take into account the
      growing trend of risk factors correlated to these diseases. In parallel, despite
      the success of vaccination programmes for polio and some childhood diseases,
      other diseases like AIDS, tuberculosis, malaria and dengue are still out of
      control in many regions of the globe. This paper is a brief review of recent
      literature dealing with communicable and non-communicable diseases in developing
      countries. It gives a global view of the main diseases and their impact on
      populations living in low- and middle-income nations.

PMID- 16274716
TI  - Survey for tuberculosis in an indigenous population of Amazonia: the Surui of
      Rondonia, Brazil.
AB  - A cross-sectional survey was carried out in 2003 to investigate the epidemiology
      of tuberculosis (TB) among the Surui Indians, Brazilian Amazon. A total of 736
      subjects (50.7% females) were examined (80% of the total population). TB suspects
      underwent standardised evaluation for the presence of signs and/or symptoms of
      active TB, including chest radiography, PPD skin test, sputum microscopy
      examination for acid-fast bacilli and mycobacterial culture. A Bacillus Calmette
      Guerin vaccine scar was detected in 699 individuals (95.0%). Of all the
      individuals examined, 120 (16.3%) had undergone previous TB treatment (46.7%
      females). One hundred and nine individuals were assessed as TB suspects (52.3%
      females). The survey identified six new cases of TB in the Surui (three men and
      three women). Five of the six cases came from only two of the ten villages.
      Mycobacterium tuberculosis colonies grew from 5 (4.6%) samples (only two of which
      were also smear-positive) and mycobacteria other than M. tuberculosis were
      isolated from 14 (12.8%) samples. Diagnosis of TB based exclusively on clinical
      grounds was established only in the case of a 4-year-old girl. Based on this
      survey, the prevalence of active TB in the sampled group (N=736) was 815.2 per
      100000. This study highlights the urgent need to review and strengthen control
      strategies directed at indigenous peoples in the country, taking into
      consideration their social, cultural and environmental differences.

PMID- 16274717
TI  - Glucocorticoids stimulate the activity of large-conductance Ca2+ -activated K+
      channels in pituitary GH3 and AtT-20 cells via a non-genomic mechanism.
AB  - The effects of glucocorticoids on ion currents were investigated in pituitary GH3
      and AtT-20 cells. In whole-cell configuration, dexamethasone, a synthetic
      glucocorticoid, reversibly increased the density of Ca2+ -activated K+ current
      (IK(Ca)) with an EC50 value of 21 +/- 5 microM. Dexamethasone-induced increase in
      IK(Ca) density was suppressed by paxilline (1 microM), yet not by glibenclamide
      (10 microM), pandinotoxin-Kalpha (1 microM) or mifepristone (10 microM).
      Paxilline is a blocker of large-conductance Ca2+ -activated K+ (BKCa) channels,
      while glibenclamide and pandinotoxin-Kalpha are blockers of ATP-sensitive and A
      type K+ channels, respectively. Mifepristone can block cytosolic glucocorticoid
      receptors. In inside-out configuration, the application of dexamethasone (30
      microM) into the intracellular surface caused no change in single-channel
      conductance; however, it did increase BKCa -channel activity. Its effect was
      associated with a negative shift of the activation curve. However, no Ca2+ 
      sensitiviy of these channels was altered by dexamethasone. Dexamethasone
      stimulated channel activity involves an increase in mean open time and a decrease
      in mean closed time. Under current-clamp configuration, dexamethasone decreased
      the firing frequency of action potentials. In pituitary AtT-20 cells,
      dexamethasone (30 microM) also increased BKCa -channel activity. Dexamethasone
      mediated stimulation of IK(Ca) presented here that is likely pharmacological,
      seems to be not linked to a genomic mechanism. The non-genomic, channel
      stimulating properties of dexamethasone may partly contribute to the underlying
      mechanisms by which glucocorticoids affect neuroendocrine function.

PMID- 16274718
TI  - S-palmitoylation modulates estrogen receptor alpha localization and functions.
AB  - 17beta-Estradiol (E2) acts as a chemical messenger in target tissues inducing
      both slow nuclear and rapid extra-nuclear responses. E2 binds to its cognate
      nuclear receptors (ER) resulting in the activation of target gene transcription
      in the nucleus. In addition to these genomic effects, E2 modulates cell functions
      through rapid non-genomic actions. Stimulation of G-proteins, Ca(2+) influx,
      inositol phosphate generation as well as phospholipase C, ERK/MAPK, and PI3K/AKT
      activation all occur within seconds to minutes after E2 binding to a small
      population of ERalpha located at the plasma membrane. The great impact of these
      rapid signals on cell physiology renders central the knowledge of the structural
      bases and mechanisms that mediate extra-nuclear signaling by E2. Several
      laboratories, including our own, have recently elucidated the structural
      requirements for localization and function of plasma membrane ERalpha. This
      review summarizes the molecular mechanisms of E2-induced rapid non-genomic
      actions relevant for cell functions, highlighting the role of lipid modification
      (i.e., palmitoylation) in the ERalpha localization to and residence at the plasma
      membrane.

PMID- 16274719
TI  - The spermatozoon of a 'living fossil': Tubiluchus troglodytes (Priapulida).
AB  - The spermatozoon of Tubiluchus troglodytes, the first priapulid formally
      described from the Mediterranean Sea has a head composed of an acrosome and a
      nucleus. The acrosome is divided in two branches coiled around the nucleus. The
      nucleus is basally columnar, but apically generates two rods helically coiled one
      around the other. The midpiece is formed by an axoneme with 27 accessory
      microtubules, surrounded by three mitochondria. An annulus separates the midpiece
      from the tail that contains a 9 + 2 axoneme surrounded by nine accessory
      microtubules. The spermatozoon of T. troglodytes is similar to that of the other
      two species known from the genus, and completely different from the 'primitive'
      one of the other priapulids. Since Tubiluchus is considered the most basal of the
      extant priapulids, and the only genus with an internal fertilization, it may be
      that in priapulids the external fertilization is a derived character.

PMID- 16274720
TI  - Effects of garlic oil and two of its major organosulfur compounds, diallyl
      disulfide and diallyl trisulfide, on intestinal damage in rats injected with
      endotoxin.
AB  - Garlic and its active components are known to possess antioxidant and
      antiinflammatory effects. The present study investigated the effects of garlic
      oil and its organosulfur compounds on endotoxin-induced intestinal mucosal
      damage. Wistar rats received by gavage 50 or 200 mg/kg body weight garlic oil
      (GO), 0.5 mmol/kg body weight diallyl disulfide or diallyl trisulfide, or the
      vehicle (corn oil; 2 ml/kg body weight) every other day for 2 weeks before being
      injected with endotoxin (i.p., 5 mg/kg body weight). Control rats were
      administered with corn oil and were injected with sterile saline. Samples for the
      measurement of proinflammatory cytokines were collected 3 h after injection, and
      all other samples were collected 18 h after injection. The low dose of GO
      suppressed endotoxin-induced inducible nitric oxide synthase (iNOS) activity,
      ulceration, and apoptosis in the intestinal mucosa (P < 0.05). The high dose of
      GO significantly lowered the peripheral level of nitrate/nitrite and endotoxin
      induced iNOS activity in the intestinal mucosa (P < 0.05) but worsened intestinal
      mucosal damage accompanied by elevated peripheral proinflammatory cytokines.
      Diallyl trisulfide but not diallyl disulfide showed similar toxic effect as that
      of high-dose GO. These results suggest the preventive effect and possible
      toxicity of garlic oil and its organosulfur compounds in endotoxin-induced
      systemic inflammation and intestinal damage.

PMID- 16274721
TI  - Overview of scorpion toxins specific for Na+ channels and related peptides:
      biodiversity, structure-function relationships and evolution.
AB  - Scorpion venoms contain a large number of bioactive components. Several of the
      long-chain peptides were shown to be responsible for neurotoxic effects, due to
      their ability to recognize Na(+) channels and to cause impairment of channel
      functions. Here, we revisited the basic paradigms in the study of these peptides
      in the light of recent data concerning their structure-function relationships,
      their functional divergence and extant biodiversity. The reviewed topics include:
      the criteria for classification of long-chain peptides according to their
      function, and a revision of the state-of-the-art knowledge concerning the surface
      areas of contact of these peptides with known Na(+) channels. Additionally, we
      compiled a comprehensive list encompassing 191 different amino acid sequences
      from long-chain peptides purified from scorpion venoms. With this dataset, a
      phylogenetic tree was constructed and discussed taking into consideration their
      documented functional divergence. A critical view on problems associated with the
      study of these scorpion peptides is presented, drawing special attention to the
      points that need revision and to the subjects under intensive research at this
      moment, regarding scorpion toxins specific for Na(+) channels and the other
      related long-chain peptides recently described.

PMID- 16274722
TI  - Norepinephrine inhibits human immunodeficiency virus type-1 infection through the
      NF-kappaB inactivation.
AB  - Exercise or acute stress can exert significant effects on immune system as well
      as cardiovascular and respiratory systems through catecholamines. In this study,
      we investigated effects of norepinephrine (NE), a catecholamine neurotransmitter
      on human immunodeficiency virus type-1 (HIV-1) infection. NE inhibited in vitro
      HIV-1 infection of peripheral blood mononuclear cells (PBMC) from healthy donors
      and ex vivo HIV-1 replication in patients' PBMC. In transient expression assays,
      NE downregulated HIV-1 long terminal repeat, but site-directed mutagenesis on NF
      kappaB-binding sites or cotreatment with H89 (a protein kinase A inhibitor)
      abrogated the NE-mediated effect. Gel-shift assays showed suppression of NF
      kappaB activity in NE-treated cells. NE increased cytoplasmic levels of IkappaB
      alpha, a natural inhibitor of NF-kappaB. Thus, NE apparently inhibits HIV-1
      infection, at least in part through NF-kappaB inactivation.

PMID- 16274723
TI  - Suppression of optokinesis during smooth pursuit eye movements revisited: the
      role of extra-retinal information.
AB  - When our eyes track objects that are moving in a richly structured environment,
      the retinal image of the stationary visual scene inevitably moves over the retina
      in a direction opposite to the eye movement. Such self-motion-induced global
      retinal slip usually provides an ideal stimulus for the optokinetic reflex. This
      reflex operates to compensate for global image flow. However, during smooth
      pursuit eye movements it must be shut down so that the reflex does not counteract
      the voluntary pursuit of moving targets. Here, we asked if retinal information is
      sufficient for this cancellation of the optokinetic reflex during smooth pursuit
      eye movements. In a series of experiments, we show that neither the eye movement
      induced retinal image motion per se nor the relative motion between the pursuit
      target and the background are sufficient for suppression of optokinesis. We,
      therefore, conclude that extra-retinal information about smooth pursuit eye
      movements is required for the cancellation of the optokinetic reflex.

PMID- 16274724
TI  - Temporal asymmetry of collinear lateral interactions.
AB  - The visibility of a target improves when the target is presented simultaneously
      or with a delay between two collinear flankers. Here we tested the temporal
      properties of lateral facilitation by manipulating the timing of both onsets and
      offsets of the target and flankers. The results show that lateral facilitation
      critically depends on the order of presentation of the target and flankers. A
      typical pattern of lateral interactions was observed when the flankers preceded
      the target, or were presented simultaneously with it, but not when the target
      preceded the flankers. This result is incompatible with a feedforward account of
      lateral interactions, according to which the two temporal effects are linearly
      summed within a higher level receptive field. We propose that both facilitation
      and masking are the result of excitatory and inhibitory interactions within
      neuronal networks. The temporal asymmetry can be accounted for by assuming
      different time courses for the excitatory and the inhibitory interactions.
      Although the excitation is slow to develop, lagging behind the stimulus both in
      onset and offset, inhibition is rapid and follows the onset and offset of the
      stimulus more closely. Such a network exhibits fast transitions between slow
      processes.

PMID- 16274725
TI  - Atmospheric carbonaceous aerosols over grasslands of central Europe and a Boreal
      forest.
AB  - A labour-intensive analytical technique was applied to atmospheric particulate
      matter samples collected in a German urban/industrial influenced grassland
      location (Melpitz) and in a Finnish forest area (Hyytiala) in order to achieve a
      detailed chemical speciation of the organic content. The representative nature of
      the solvent and water-extractable fractions was determined. The organic compounds
      identified in the solvent extracts are represented by primary compounds with both
      anthropogenic and biogenic origin, which mainly derive from the vegetation waxes
      and from petrogenic sources. Secondary products resulting from the oxidation of
      volatile organic compounds were also detected. The German meadow presented the
      highest levels of sugars and acidic compounds in the water extracts, whilst
      polyols were the most abundant class in the Finnish forest. The major compounds
      of these classes were malic acid, mannitol, arabitol, glucose and sucrose.
      Levoglucosan was also found in the water extract.

PMID- 16274726
TI  - Mechanisms of hypoxic tolerance in presymptomatic APP23 transgenic mice.
AB  - In the B6-Tg (ThylAPP)23Sdz (APP23tg) transgenic mouse model of Alzheimer's
      disease hypoxic tolerance is impaired prior to amyloid deposition. We therefore
      investigated mechanisms known to mediate resistance to hypoxic episodes in
      presymptomatic APP23tg and appropriate control strains. The mRNA expression
      levels in the hippocampus of adenosine receptor subtypes A1 and A3, estrogen
      receptors alpha and beta, progesterone receptor, and neuronal and endothelial
      nitric oxide synthase were investigated with semi-quantitative RT-PCR. Mice were
      pretreated in vivo with a low dose of 3-nitropropionate, an inhibitor of succinic
      dehydrogenase, known to mediate hypoxic tolerance within 1h. We found increased
      expression levels in presymptomatic, untreated APP23tg animals of adenosine A3
      receptor mRNA and estrogen receptor alpha mRNA. In addition, we observed an
      increase in nNOS expression levels upon mild cellular hypoxia induced by 3-NP in
      transgenic but not in wild-type animals. We conclude that overexpression of human
      APP results in differential expression of receptors conferring hypoxic tolerance
      prior to amyloid deposition. Up-regulation of nNOS expression levels upon hypoxic
      challenge in APP23tg transgenic animals may therefore reflect a selective
      vulnerability in these animals even before amyloid deposition.

PMID- 16274727
TI  - Juvenile Huntington's disease: does a dosage-effect pathogenic mechanism differ
      from the classical adult disease?
AB  - Huntington's disease (HD) is caused by a CAG repeat mutation translating as a
      polyglutamine (poly(Q)) expansion in the huntingtin protein, whose main
      pathogenic mechanism is a gain of toxic function. In the case of large expansions
      beyond 60 repeats onset may result in juvenile HD (JHD, onset before 20 years of
      age). However, the triplet number does not represent the only onset modifier even
      in case of large expansions, mechanisms other than the size of the mutation
      contribute to the phenotype. In this review we discuss the possibility that some
      of the pathogenic mechanisms contributing to age at onset and progression may
      differ in the early onset HD compared with the classical adult pathology.

PMID- 16274728
TI  - Diagnosing prodromal Alzheimer's disease: role of CSF biochemical markers.
AB  - Mild cognitive impairment (MCI) is an aetiologically heterogeneous syndrome. A
      correct prediction of MCI conversion to Alzheimer's disease (AD) represents a
      primary goal in routine clinical practice. Since the presence of pathological
      levels in >or=2 cerebrospinal fluid (CSF) biomarkers; amyloid protein (Abeta42),
      total tau (h-tau) and phospho-tau (p-tau) seems to reliably identifying MCI
      subjects converting to AD, we report our experience in a routine clinical
      setting. In the period from January 2001 to June 2003, 273 consecutive patients
      referred to our Memory Clinic for diagnostic assessment of cognitive impairment.
      Of them, 180 underwent a complete diagnostic evaluation including CSF dosage of
      fragment 1-42 of amyloid protein, total tau and phospho-tau (ELISA Method,
      Innogenetics, Gent, Belgium), after vascular or other secondary causes of
      dementia could be excluded. At baseline, 38% of the MCI subjects (20/55) showed
      pathological levels in >or=2 CSF biomarkers. After 1 year, 11 MCI patients
      converted to dementia, 33 remained stable, 11 showed a further progression of
      cognitive impairment still not fulfilling the diagnostic criteria for dementia.
      Of the 11 converters, 10 showed >or=2 pathological values CSF biomarkers and in
      all of them, p-tau was high. On the contrary, 29 out of 33 stable MCI (88%)
      showed no or one pathological CSF value. We confirm that pathological levels in
      >or=2 CSF biomarkers reliably predict MCI conversion to AD and correctly identify
      the stable form of MCI.

PMID- 16274729
TI  - On the mechanisms of ageing suppression by dietary restriction-is persistent
      glycolysis the problem?
AB  - The mechanism(s) by which dietary restriction (DR) suppresses ageing and onset of
      age-related pathologies are discussed in relation to frequency of glycolysis, and
      the reactivity of glycolytic intermediates. Most glycolytic intermediates are
      potentially toxic and readily modify (i.e. glycate) proteins and other
      macromolecules non-enzymically. Attention is drawn to the reactivity of
      methyglyoxal (MG) which is formed predominantly from the glycolytic intermediates
      dihydroxyacetone- and glyceraldehyde-3-phosphates. MG rapidly glycates proteins,
      damages mitochondria and induces a pro-oxidant state, similar to that observed in
      aged cells. It is suggested that because DR animals' energy metabolism is less
      glycolytic than in those fed ad libitum, intracellular MG levels are lowered by
      DR The decreased glycolysis during DR may delay senescence by lowering
      intracellular MG concentration compared to ad libitum-fed animals. Because of the
      reactivity MG and glycolytic intermediates, occasional glycolysis could be
      hormetic where glyoxalase, carnosine synthetase and ornithine decarboxylase are
      upregulated to control cellular MG concentration. It is suggested that in ad
      libitum-fed animals persistent glycolysis permanently raises MG levels which
      progressively overwhelm protective processes, particularly in non-mitotic
      tissues, to create the senescent state earlier than in DR animals. The possible
      impact of diet and intracellular glycating agents on age-related mitochondrial
      dysfunction is also discussed.

PMID- 16274730
TI  - Do landscape factors affect brownfield carabid assemblages?
AB  - The carabid fauna of 28 derelict sites in the West Midlands (England) were
      sampled over the course of one growing season (April-October, 1999). The study
      aimed to investigate the relationship between carabid assemblages and five
      measures of landscape structure pertinent to derelict habitat. At each site
      measurements of landscape features pertinent to derelict habitat were made: (i)
      the proximity of habitat corridors; (ii) the density of surrounding derelict
      land; (iii) the distance between the site and the rural fringe; and (iv) the size
      of the site. Concurrent surveys of the soil characteristics, vegetation type, and
      land use history were conducted. The data were analysed using a combination of
      ordination (DCA, RDA), variance partitioning (using pRDA) and binary linear
      regression. The results suggest that: 1. There is very little evidence that the
      carabid assemblages of derelict sites were affected by landscape structure, with
      assemblages instead being principally related to within-site habitat variables,
      such as site age (since last disturbance), substrate type and vegetation
      community. 2. No evidence was found to support the hypothesis that sites away
      from railway corridors are impoverished in their carabid fauna than sites on
      corridors. 3. There are some suggestions from this study that rarer and non
      flying specialist species may be affected by isolation, taking longer to reach
      sites. We infer from this that older sites with retarded succession, and sites in
      higher densities of surrounding derelict land may eventually become more species
      rich and that these sites may be important for maintaining populations of rarer
      and flightless species. 4. Conservation efforts to maintain populations of these
      species should focus principally on habitat quality issues, such as maintaining
      early successional habitats that have a diversity of seed producing annuals and
      perennial plants and enhancing substrate variability rather than landscape
      issues.

PMID- 16274731
TI  - Efficiency of industrial minerals on the removal of mercury species from liquid
      effluents.
AB  - Increasing attention has been given, by the industrial sector, to the removal of
      heavy metals from liquid effluents to satisfy environmental regulations. For this
      purpose, the most common methods utilized include: chemical precipitation,
      cementation, ion exchange, adsorption and solvent extraction. All these methods
      have limitations such as slow kinetics, low adsorption capacity and they are
      usually very expensive. Thus, new technologies for heavy metal removal are of
      great interest. This study consisted on a screening of industrial minerals to
      check their efficiencies to remove mercury from liquid effluents. The methodology
      employed a batch adsorption technique. The tested minerals included: atapulgites,
      zeolites, magnetites, kaolin, vermiculite and bentonite. Results show relatively
      high efficiencies of magnetite and zeolite on mercury removal. These minerals
      were capable to remove mercury species from effluents with concentrations
      reaching 1,000 ppm, corresponding to a sorption capacity of 10,000 mg Hg/kg. The
      sorption maximum was not reached in these tests. In addition, it became evident
      the importance of mercury speciation at the solid:liquid interface, with relevant
      consequences on the application of this technology to effluent treatment.

PMID- 16274732
TI  - Chemical and biochemical parameters of cultured diatoms and bacteria from the
      Adriatic Sea as possible biomarkers of mucilage production.
AB  - Bacteria and diatom strains from the Adriatic Sea were investigated, under
      standard and altered environmental conditions, for carbohydrate production and
      for the presence of specific biomarkers. Algae from P-depleted cultures showed an
      increase in extracellular carbohydrate production, a significantly lower
      chlorophyll a content and unchanged total lipid levels. However, the fatty acid
      composition of algal cultures was severely affected by low P levels, in that,
      total saturated and monounsaturated fatty acids increased and total
      polyunsaturated fatty acids decreased. Marine heterotrophic bacteria resulted
      enriched by 4 to 6 orders of magnitude in mucilage samples respect to surrounding
      seawater, unlike other groups of bacteria such as the non-halophylic
      heterotrophs. The major fatty acids detected in bacteria were 16:0 and 18:1n-7;
      the uneven fatty acids 17:0i, 17:0 and 17:1 also constituted an important
      component of various strains and, as a result, the total monounsaturated fraction
      represented the main component of total fatty acids. All the mucilage samples
      analysed shared the same general fatty acid composition features with a high
      amount of saturated components, especially 16:0; typical marine polyunsaturated
      fatty acids, such as 20:5n-3 and 22:6n-3, were found at very low levels. With
      regard to the sterol composition, the analysed algal species and bacteria showed
      that different compounds prevailed in the different species, and under P
      deprivation sterol distribution resulted differently affected in the various
      algal species. In mucilage samples an overall prevalence of cholesterol was
      observed and, among 4alpha-methylsterols, constantly present, dinosterol
      prevailed in all samples. Vibrational IR spectroscopic analyses confirmed the
      main results obtained with the GC analysis: a higher unsaturation degree in
      nutrient replete diatom cultures than in P-depleted ones, a lower amount of P
      containing compounds in the latter, bacterial lipid profiles with a high amount
      of free carboxylic acids and/or ketones and a low unsaturation degree and,
      finally, mucilage samples with a very low unsaturation degree. All these results
      allowed some speculations on the involvement of the various microbial and
      phytoplankton components in mucilage genesis.

PMID- 16274733
TI  - Calculation of the mercury accumulation in the Idrijca River alluvial plain
      sediments.
AB  - From the historic literature on the Idrija mercury mine, it is evident that part
      of the smelting and mining waste was dumped into the Idrijca River. This waste
      was transported downstream during floods. The amount of mercury which has
      accumulated in the alluvial sediments of the Idrijca River until the present was
      studied. Mapping of Holocene river terraces of the Idrijca River was performed in
      order to estimate the volume of the alluvial sediment. For the purpose of the
      assessment of the mercury concentration, we sampled the alluvial sediments on
      different levels and performed an analysis of variance. The greatest variability
      is between the floodplain and terraces inside the same alluvial plain.
      Considering this fact, which determined the methodology employed for calculation,
      we estimated that about 2029 tons of mercury is stored in the Idrijca River
      alluvial sediments.

PMID- 16274734
TI  - Anticoagulation plus aspirin following acute myocardial infarction: yes or no ...
      and if the latter, why not?

PMID- 16274735
TI  - Endothelial function is impaired in patients with primary antiphospholipid
      syndrome.
AB  - INTRODUCTION: The aim of this study was to evaluate endothelial function in
      patients with primary antiphospholipid syndrome (PAPS). PATIENTS AND METHODS:
      Flow mediated (FMD) and glyceryl trinitrate (GTN) induced dilation of the right
      brachial artery were studied in 25 patients with PAPS and 25 controls matched by
      age, sex and conventional risk factors for atherosclerosis. Fibrinogen, D-dimer,
      adhesion molecules, tissue plasminogen activator (t-PA) and plasminogen activator
      inhibitor-1 (PAI-1) antigens and activities were measured. RESULTS: Mean (SD) FMD
      was significantly lower in PAPS than in controls (8+/-5% vs. 15+/-6%, P<0.001);
      GTN-induced dilation did not differ between the groups. There was a correlation
      between the baseline diameter of the brachial artery and duration of the disease
      (-0.56, P<0.05) and between GTN induced dilation and duration of the disease
      (0.51, P<0.05). Concentrations of vascular cell adhesion molecule-1 (P<0.001),
      intracellular adhesion molecule-1 (P<0.001) and fibrinogen (P<0.05) were higher
      in patients than in controls but no differences were observed for D-dimer, t-PA
      and PAI-1 antigens and activities. There was correlation between concentration of
      vascular cell adhesion molecule-1 and FMD (-0.35, P<0.05) and between
      intracellular adhesion molecule-1 and FMD (-0.41, P<0.05). CONCLUSIONS: This
      study shows that endothelial function is impaired in patients with primary APS,
      possibly contributing to accelerated atherosclerosis and thromboembolic
      complications in these patients.

PMID- 16274736
TI  - Enoxaparin-induced psoas hematoma complicated by Staphylococcus aureus infection
      after cardiac catheterization.

PMID- 16274737
TI  - HIV impact on acute morbidity and pelvic tumor control following radiotherapy for
      cervical cancer.
AB  - OBJECTIVE: To determine the impact of HIV infection on acute morbidity and pelvic
      tumor control following external beam radiotherapy (EBRT) for cervical cancer.
      METHOD: 218 patients receiving EBRT who also had HIV testing after informed
      consent was obtained were evaluated. Acute treatment toxicity was documented
      weekly during treatment and 1 month post-EBRT. Pelvic tumor control was
      documented at 4 and 7 months post-EBRT. Clinicians were blinded for HIV results.
      RESULTS: About 20% of the patients were HIV-positive. Overall, 53.4% of the
      patients had radiation-related acute toxicity (grade 3-4). HIV infection was
      associated with a 7-fold higher risk of multisystem toxicity: skin,
      gastrointestinal tract (GIT) and genitourinary tract (GUT) systems. It was also
      an independent risk factor for treatment interruptions (adjusted relative risk
      2.2). About 19% of the patients had residual tumor at 4 and 7 months post-EBRT.
      HIV infection was independently and significantly associated with 6-fold higher
      risk of residual tumor post-EBRT. The hazard ratio of having residual tumor after
      initial EBRT was 3.1-times larger for HIV-positive than for HIV-negative patients
      (P = 0.014). CONCLUSION: HIV is associated with increased risk of multisystem
      radiation-related toxicity; treatment interruptions and pelvic failure (residual
      tumor) following EBRT. HIV infection is an adverse prognostic factor for outcome
      of cervical cancer treatment.

PMID- 16274738
TI  - Groin recurrence following Stage 1A squamous cell carcinoma of the vulva.
AB  - BACKGROUND: It has been well established that stage 1 squamous cell carcinomas of
      the vulva with a depth of stromal invasion less than 1 mm have a <1% risk of
      lymph node involvement. The treatment for these stage 1A tumours has therefore
      been to perform radical wide local excision without removal of groin nodes. CASE:
      We present two cases of stage 1A microinvasive cancer of the vulva that presented
      with groin recurrence 3 months and 3 years following their primary surgery
      respectively. CONCLUSION: The current management of stage 1A tumours may need to
      be re-evaluated to include some form of lymph node assessment in view of these
      rare but nonetheless aggressive tumours.

PMID- 16274739
TI  - The role of developmental assets in predicting academic achievement: a
      longitudinal study.
AB  - A sample of 370 students in the 7th-9th grades in 1998 was followed for 3 years
      through the 10th-12th grades in order to investigate the relation of
      "developmental assets"--positive relationships, opportunities, skills, values,
      and self-perceptions--to academic achievement over time, using actual GPA as the
      key outcome variable. The greater the number of developmental assets students
      reported in the 7th-9th grades, the higher their GPA in the 10th-12th grades.
      Students who stayed stable or increased in their asset levels had significantly
      higher GPAs in 2001 than students whose asset levels decreased. Increases in
      assets were significantly associated with increases in GPA. Experiencing in 1998
      clusters of specific assets increased by 2-3 times the odds of students having a
      B+ or higher GPA in 2001. The results offer promising evidence that a broad focus
      on building the developmental nutrients in young people's lives may contribute to
      academic success.

PMID- 16274740
TI  - A novel matrix for the immobilization of acetylcholinesterase.
AB  - In this study, a new matrix for immobilization of acetylcholinesterase was
      investigated by using alginate and kappa-carrageenan. The effects of pH,
      temperature, storage and thermal stability on the free and immobilized
      acetylcholinesterase activity were examined. Maximum reaction rate (V(max)) and
      Michaelis-Menten constant (K(m)) was also investigated for free and immobilized
      enzymes. For free and immobilized enzymes into Ca-alginate and alginate/kappa
      carrageenan polymer blends, optimum pH and temperature was found to be 7 and 30
      degrees C, respectively. For free enzyme, maximum reaction rate (V(max)) and
      Michaelis-Menten constant (K(m)) values were found to be 6.35 mM and 50 mM min(
      1), respectively, the same values for immobilized enzymes were determined as
      8.68, 12.7 mM and 39.7, 52.9 mM min(-1), respectively. Storage and thermal
      stability of acetylcholinesterase was increased by as a result of immobilization.

PMID- 16274741
TI  - Measuring poly-victimization using the Juvenile Victimization Questionnaire.
AB  - OBJECTIVE: Children who experience multiple victimizations (referred to in this
      paper as poly-victims) need to be identified because they are at particularly
      high risk of additional victimization and traumatic psychological effects. This
      paper compares alternative ways of identifying such children using questions from
      the Juvenile Victimization Questionnaire (JVQ). METHODS: The JVQ was administered
      in a national random digit dial telephone survey about the experiences of 2,030
      children. The victimizations of children 10-17 years old were assessed through
      youth self-report on the JVQ and the victimizations of children 2-9 assessed
      through JVQ caregiver proxy report. RESULTS: Twenty-two percent of the children
      in this sample had experienced four or more different kinds of victimizations in
      separate incidents (what we term poly-victimization) within the previous year.
      Such poly-victimization was highly associated with traumatic symptomatology.
      Several ways of identifying poly-victims with the JVQ produced roughly equivalent
      results: a simple count using the 34 victimizations screeners, a count using a
      reduced set of only 12 screeners, and the original poly-victimization measure
      using follow-up questions to identify victimizations occurring during different
      episodes. CONCLUSION: Researchers and clinicians should be taking steps to
      identify poly-victims within the populations with which they work and have
      several alternative ways of doing so.

PMID- 16274742
TI  - Pb(II)-binding capability of aminohydroxamic acids: primary hydroxamic acid
      derivatives of alpha-amino acids as possible sequestering agents for Pb(II).
AB  - Complexes of aminohydroxamic acids, D,L-alpha-alaninehydroxamic acid (alpha
      Alaha), sarcosinehydroxamic acid (Sarha), D,L-N-methyl-alpha-alaninehydroxamic
      acid (N-Me-alpha-Alaha), beta-alaninehydroxamic (beta-Alaha), L-aspartic acid
      beta-hydroxamic acid (Asp-beta-ha), L-glutamic acid-gamma-hydroxamic acid (Glu
      gamma-ha) and L-histidinehydroxamic acid (Hisha) with lead(II) in aqueous
      solution were studied by pH-potentiometric, 1H NMR and electrospray ionization
      mass spectrometric (ESI MS) methods. The results were compared to those of a
      simple monohydroxamic acid, acetohydroxamic acid and the effects of the amino
      group, hydroxamate-N, as well as, additional side chain donors on the co
      ordination mode and on the stability of the complexes formed were evaluated. It
      was found that the amino nitrogen atom situating in beta- or in gamma-position
      (beta-Alaha, Asp-beta-ha, Glu-gamma-ha) does not co-ordinate to Pb(II), only
      hydroxamate type chelates are formed before the hydrolytic processes. However,
      the amino-N in alpha-position (alpha-Alaha, Sarha, Hisha) seems to form a stable
      5-membered (N,N)-type chelate together with the deprotonated hydroxamate-N above
      pH 6. On the other hand, the hydroxamate (O,O)-type chelate also exists. Since
      steric reasons do not allow the coordination of these two chelates of a molecule
      to the same Pb(II) ion, polynuclear complexes with mixed co-ordination modes are
      formed with the alpha-derivatives above pH 6. Simple hydroxamate type complexes
      are formed with N-Me-alpha-Alaha, where the hydroxamate-N is not able to co
      ordinate. The co-ordination of the side chain imidazole of Hisha is not
      measurable, while a weak interaction of the side chain carboxylates of Asp-beta
      ha and especially of Glu-gamma-ha can be suggested.

PMID- 16274743
TI  - Pseudomonas stutzeri pneumonia in an HIV seropositive patient.

PMID- 16274744
TI  - Successful treatment of post-kala-azar dermal leishmaniasis (PKDL) in a HIV
      infected patient with multiple relapsing leishmaniasis from Western Europe.
AB  - We present a 42-year-old man who was admitted with worsening of his general
      condition and facial skin lesions. He had previously been diagnosed with HIV
      infection and visceral leishmaniasis (VL). Diagnostic work-up revealed a new
      relapse of VL paralleled by the diagnosis of post-kala-azar dermal leishmaniasis
      (PKDL). The patient was treated with IV liposomal amphotericin B as well as
      sodium stibogluconate followed by oral hexadecylphosphocholine (miltefosine) over
      a period of 9 months. PKDL lesions began to disappear after 8 months of
      treatment. In addition, severe and relapsing VL so far remains in remission. This
      case demonstrates successful treatment of PKDL and relapsing VL in a Western
      European patient with HIV infection.

PMID- 16274745
TI  - Recurrent vacuolar myelopathy in HIV infection.
AB  - OBJECTIVES: Vacuolar myelopathy is the major cause of spinal cord disease in HIV
      1 infection. However, the pathogenesis remains unclear. Diagnosis is mainly based
      on characteristic clinical symptoms in combination with characteristic MRI
      changes. Usually, it is a slowly progressive chronic disease affecting HIV
      infected individuals with low CD4 T-cell counts. CASE: Here, we report an
      uncommon case of vacuolar myelopathy in an HIV-infected woman with recurrent
      clinical symptoms and MRI changes of vacuolar myelopathy and with a preserved CD4
      T-cell count when symptoms occurred for the first time. CONCLUSIONS: This is the
      first case, to show that vacuolar myelopathy can have relapsing-remitting
      clinical symptoms and MRI changes.

PMID- 16274746
TI  - Candida albicans endocarditis treatment with caspofungin in an HIV-infected
      patient--case report and review of literature.
AB  - Caspofungin has recently been introduced for the treatment of invasive
      candidiasis, however, there is limited data on its use in endocarditis. We report
      a 22-year-old male HIV-infected patient on methadone maintenance therapy that
      developed right-sided Candida albicans endocarditis. Caspofungin treatment and
      vegetectomy, followed by fluconazole, was successful in the treatment of our
      patient. We also review all previous cases of Candida endocarditis treated with
      caspofungin.

PMID- 16274747
TI  - The somatostatin sst1 receptor: an autoreceptor for somatostatin in brain and
      retina?
AB  - The sst1 receptor was the first of the 5 somatostatin receptors to be cloned by
      homology with the glucagon receptor 13 years ago. It is a 7-transmembrane domain
      G-protein-coupled receptor that is negatively coupled to adenylyl cyclase, but
      can also trigger other transduction pathways. The distribution of sst1 mRNA,
      immunolabeling, and radioligand binding are not entirely overlapping, but the
      recent availability of knockout (KO) mice and a (still limited) number of
      selective agonists/antagonists has increased our knowledge about this receptor.
      These new tools have helped to reveal a role for the sst1 receptor in
      hippocampal, hypothalamic, basal ganglia, and retinal functions. In at least the
      latter 3 structures, the sst1 receptor appears to act as an inhibitory
      autoreceptor located on somatostatin neurons, whereas in the hippocampus such a
      role is still based on circumstantial evidence.

PMID- 16274748
TI  - The cell cycle as a therapeutic target for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most prevalent neurodegenerative disease
      worldwide. It is a progressive, incurable disease whose predominant clinical
      manifestation is memory loss, and which always ends in death. The classic
      neuropathological diagnostic markers for AD are amyloid plaques and
      neurofibrillary tangles, but our understanding of the role that these features of
      AD play in the etiology and progression of the disease remains incomplete.
      Research over the last decade has revealed that cell cycle abnormalities also
      represent a major neuropathological feature of AD. These abnormalities appear
      very early in the disease process, prior to the appearance of plaques and
      tangles. Growing evidence suggests that neuronal cell cycle regulatory failure,
      leading to apoptosis, may be a significant component of the pathogenesis of AD. A
      number of signaling pathways with the potential to activate aberrant cell cycle
      re-entry in AD have been described. The relationships among these signaling
      cascades, which involve the amyloid precursor protein (APP), cyclin-dependent
      kinases (cdks), and the cell cycle protein Pin1, have not yet been fully
      elucidated, but details of the individual pathways are beginning to emerge. This
      review summarizes the current state of knowledge with respect to specific
      neuronal signaling events that are thought to underlie cell cycle regulatory
      failure in AD brain. The elements of these pathways that represent potential new
      therapeutic targets for AD are described. Drugs and peptides that can inhibit
      molecular steps leading to AD neurodegeneration by intervening in the activation
      of cell cycle re-entry in neurons represent an entirely new approach to the
      development of treatments for AD.

PMID- 16274749
TI  - CNS injury research; reviewing the last decade: methodological errors and a
      proposal for a new strategy.
AB  - During the last decades the field of Traumatic Brain Injury (TBI) has been
      characterized by a paucity of new treatments. This is in contrast to the amount
      of pre-clinical experimental work and the number of clinical trials done. This
      paper aims to contribute to the ongoing debate on the reasons that have led to
      this phenomenon. A reasonable suggestion could be the presence of methodological
      limitations when comparing and integrating experimental results. The first
      methodological drawback, which is shortly discussed, is the insistence (during
      the last decades) on the concept of "similarity to the human pathology" as the
      main criterion to evaluate results, and the constant effort to create a "super
      model" that would fully replicate human TBI cases. The second methodological
      limitation examined is the lack of a common way to present and analyze data. It
      is proposed that the basic neuro-histo-pathology of each injury model should
      serve as the ground on which hypotheses should be built, as it could constitute
      the common basis for comparisons between different experimental settings. In this
      context, 95 papers reporting experimental results from various models of animal
      CNS injury were reviewed in order to examine the extent to which results were
      presented and analyzed using a common basis. No such common basis was observed;
      moreover, the review revealed a remarkable lack of histopathological examination
      of the animals, especially when biochemical and/or behavioral endpoints were
      assessed. It is argued that this practice deprives data of an objective common
      basis. Conclusively, a new theoretical way of organizing experimental work in the
      field of TBI is briefly presented.

PMID- 16274750
TI  - Examining differential effects of psychological treatment of depressive disorder:
      an application of trajectory analyses.
AB  - BACKGROUND: Although different psychological treatments of depression seem
      equally effective, studies in this area have not taken sufficient account of the
      heterogeneity among patients. Modern techniques for longitudinal data analysis
      can be helpful in examining differential effects of psychological interventions
      on specific subpopulations of patients. METHODS: Outpatients in mental health
      care, diagnosed with DSM-IV major depressive disorder, were randomly assigned to
      cognitive behavior therapy (N=199) or treatment as usual (N=226). Every 3 months
      for a total of 1.5 years, depressive symptomatology was measured using the SCL
      90. Growth mixture modeling techniques were used to identify different trajectory
      classes of patients. The impact of type of treatment (treatment as usual vs.
      cognitive behavior therapy) was examined for each identified trajectory. RESULTS:
      On average, patients in both test conditions improved significantly from baseline
      to posttest, and no significant difference was found between the conditions.
      However, four different trajectory classes could be distinguished within the
      sample. Most patients were classified into the two classes with the lowest
      depression scores at baseline (31% and 33% of the total sample). For these two
      classes, no significant differences in the course of depressive symptoms were
      found between the two conditions. In the two classes with the more severe
      depression scores (10% and 26% of the sample), however, cognitive behavior
      therapy was significantly more effective than treatment as usual. CONCLUSIONS:
      Although different treatments may seem to be equally effective, this does not
      have to be true for all classes of patients. Longitudinal research on the
      treatment of mental disorders should take heterogeneity among patients into
      account.

PMID- 16274751
TI  - Development of a new microwell hybridization assay and an internal control RNA
      for the detection of porcine noroviruses and sapoviruses by reverse transcription
      PCR.
AB  - Recently, genetically diverse porcine noroviruses (NoV) and sapoviruses (SaV)
      were identified from field pig fecal samples. Reverse transcription (RT)-PCR is
      the primary method used for detection of human NoVs and SaVs. However, RT-PCR
      inhibitors frequently cause false-negative results. In this study, a competitive
      internal control (IC) RNA, specific for use in the SaV RT-PCR assay, was
      developed to monitor inhibition of RT-PCR; primers for detection of genetically
      diverse porcine NoVs and SaVs were designed; and microwell hybridization assays
      to confirm the specific RT-PCR products were developed. The primer pairs and the
      RT-PCR-hybridization combinations were compared using representative porcine NoV
      and SaV strains, positive pig fecal samples and a panel of 30 field pig fecal
      samples. Extracted RNA from 3 of 30 samples failed to amplify the IC RNA.
      However, this inhibition was not present after a 10-fold dilution of the
      extracted RNA. The five different RT-PCR-hybridization combinations developed
      specifically detected all three genotypes of porcine NoVs, all GIII porcine SaVs,
      unclassified JJ681-like, QW19 and LL26-like porcine SaVs, respectively. These RT
      PCR-hybridization assays are specific, less time consuming and economical and
      particularly applicable to testing large number of samples for porcine NoVs and
      SaVs.

PMID- 16274752
TI  - Development of quantitative gene-specific real-time RT-PCR assays for the
      detection of measles virus in clinical specimens.
AB  - Real-time RT-PCR assays targeting sequences in the measles virus (MV)
      nucleoprotein (N), fusion (F), and hemagglutinin (H) genes were developed for the
      detection of MV RNA in clinical specimens. Four primer and probe sets each for
      the N, F, and H genes were evaluated and reaction conditions optimized. Using
      dilution series of synthetic RNAs, the limits of detection were determined to be
      approximately 10 copies for each target RNA/reaction. The relationship between
      C(t) values and RNA concentration was linear within a range of 10-10(6) RNA
      copies/reaction, and intra- and inter-assay variability was low. The N gene
      specific real-time assay detected MV RNA in 100% of clinical samples from
      confirmed measles cases compared to 41% by standard RT-PCR. The MV H and F gene
      specific real-time assays detected MV RNA in 93% and 82% of these specimens,
      respectively. Real-time assays could detect RNA from strains representing each
      active genotype of MV and were also highly specific, as no false positives were
      identified when samples known to contain other respiratory viruses were tested.
      Real-time RT-PCR assays will be available to support routine measles laboratory
      surveillance, to facilitate research projects on pathogenesis that require
      sensitive and quantitative detection of MV RNA, and to aid in the investigation
      of serious disease sequelae resulting from natural measles infection or
      vaccination with measles-containing vaccines.

PMID- 16274753
TI  - Regulatory studies of murine methylenetetrahydrofolate reductase reveal two major
      promoters and NF-kappaB sensitivity.
AB  - Two promoters of the murine methylenetetrahydrofolate reductase gene (Mthfr), a
      key enzyme in folate metabolism, were characterized in Neuro-2a, NIH/3T3 and RAW
      264.7 cells. Sequences of 189 bp and 273 bp were sufficient to achieve maximal
      activity of the upstream and downstream promoter, respectively. However, subtle
      differences in minimal promoter lengths and in promoter activities were observed
      between the cell lines. Both promoters demonstrated comparable activity in
      NIH/3T3 and RAW 264.7 cells, while in Neuro-2a cells, the upstream promoter was
      15-fold more active than the downstream promoter. Alignment and data mining tools
      identified a candidate nuclear factor kappa B (NF-kappaB) binding site at the
      3'end of the downstream promoter that is conserved throughout several species. NF
      kappaB activation experiments in cultured cells were associated with increased
      Mthfr mRNA. Co-transfection of NF-kappaB and promoter constructs demonstrated
      Mthfr up-regulation by at least 2-fold through its downstream promoter in Neuro
      2a cells; this increase was significantly reduced when the putative binding site
      was mutated. EMSA analysis demonstrated direct binding of NF-kappaB to this non
      mutated site. This study, a first step into the elucidation of Mthfr regulation,
      demonstrates that two TATA-less, GC-rich promoters differentially drive
      transcription of Mthfr in a cell-specific manner, and provides a novel link of
      Mthfr to possible roles in the immune response and cell survival.

PMID- 16274754
TI  - Use of Forster's resonance energy transfer microscopy to study lipid rafts.
AB  - Rafts in cell membranes have been a subject of much debate and many models have
      been proposed for their existence and functional significance. Recent studies
      using Forster's resonance energy transfer (FRET) microscopy have provided one of
      the first glimpses into the organization of putative raft components in living
      cell membranes. Here we discuss how and why FRET microscopy provides an
      appropriate non-invasive methodology to examine organization of raft components
      in cell membranes; a combination of homo and hetero-FRET microscopy in
      conjunction with detailed theoretical analyses are necessary for characterizing
      structures at nanometre scales. Implications of the physical characteristics of
      the organization of GPI-anchored proteins in cell membranes suggest new models of
      lipid-based assemblies in cell membranes based on active principles.

PMID- 16274755
TI  - Looking glass inhibitors: efficient synthesis and biological evaluation of D
      deoxyfuconojirimycin.
AB  - 1,6-Dideoxygalactostatin, the mirror image of 1-deoxy-L-fuconojirimycin, was
      efficiently prepared from 2,3-O-isopropylidene-L-lyxonolactone in four steps and
      evaluated as a glycosidase inhibitor.

PMID- 16274756
TI  - Chemoenzymatic synthesis of the 3-sulfated Lewisa pentasaccharide.
AB  - The sulfated pentasaccharide benzyl O-(3-O-sulfo-beta-D-galactopyranosyl)-(1-->3)
      O-[(alpha-L-fucopyranosyl)-(1-->4)]-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)
      (1-->3)-O-(beta-D-galactopyranosyl)-(1-->4)-O-beta-D-glucopyranoside sodium salt
      was synthesized using a chemo-enzymatic approach. Lacto-N-tetraose, obtained from
      two disaccharides [4-methoxybenzyl O-(2,3,4,6-tetra-O-acetyl-beta-D
      galactopyranosyl)-(1-->3)-4,6-O-benzylidene-2-deoxy-2-phtalimido-beta-D
      glucopyranoside and benzyl 2,6-di-O-acetyl-beta-D-galactopyranosyl-(1-->4)-2,3,6
      tri-O-acetyl-beta-D-glucopyranoside], was regioselectively sulfated at the 3 OH
      position of the terminal galactose using the stannylene procedure. The
      fucosylation of the sulfated tetrasaccharide was performed using soluble or
      immobilized fucosyltransferase FucT-III to give the title compound.

PMID- 16274757
TI  - The structure of a polysaccharide isolated from Inonotus levis P. Karst. mushroom
      (Heterobasidiomycetes).
AB  - Inonotus levis biomass was extracted with 5% NaOH containing NaBH4, the insoluble
      material was discarded and the solution dialyzed. It was further treated with
      proteinase and the polymeric fraction isolated by gel chromatography. It
      contained mostly a polysaccharide of the following structure: where a non
      reducing terminal glucuronic acid residue was present in about half of the
      molecules, making thus some of the chains acidic and others neutral. Methyl
      groups were present at about half of the galactose residues, however, no direct
      proof of the presence of defined repeating units was obtained due to NMR signals
      overlap. We believe that these short polymeric chains might be originally
      attached to a protein via serine or threonine residues and were cleaved off due
      to the alkaline conditions of extraction. Another polymer, co-extracted with this
      galactan, was a branched phosphorylated mannan with a structure similar to that
      of the mannan from Saccharomyces cerevisiae yeast.

PMID- 16274758
TI  - The prevalence and risk factors of dementia in the elderly population in a low
      socio-economic region of Izmir, Turkey.
AB  - The aim of this study is to determine the prevalence of and risk factors of
      dementia in the elderly with a low socio-economical status. The study is a cross
      sectional and analytic study. Two hundred and four persons aged 65 years and
      above were selected by using the cluster sampling method. The presence of
      dementia was determined by Standardized Mini Mental State Examination (SMMSE).
      Twenty-three and 18 cut-off points were accepted as the existence of dementia in
      educated and uneducated older individuals, respectively. Chi-square test,
      Student's t-test, and logistic regression analysis were used for data analysis.
      The mean age of older subjects was 70.8+/-6.45 (S.D.); 71.5+/-5.9 in males and
      70.3+/-6.8 in females (p=0.19). Ninety-one percent of older people had never
      attended school, 54.6% were living below the poverty level, and 97% of the
      residences were in squatter settlements. Dementia was determined in 46 older
      subjects (22.9%). Dementia was found significantly higher in females, in elderly
      subjects aged 80 years and above, in older subjects who were in a bad or very bad
      self-health status and in those who had a chronic disease, did not have any
      occupation, had a lower monthly income, and with a depressive score eight and
      above (p<0.05). In our study, the prevalence of dementia in older people was
      higher, in agreement with many reported studies. We assumed that this was due to
      the fact that the ratio of the uneducated, poor, and advanced aged subjects in
      this study was considerably higher. The different prevalence rates in studies
      demonstrate that the adoption of SMMSE for the study population, the validity
      reliability analyses of tests and the standardization of diagnostic criteria are
      necessary.

PMID- 16274759
TI  - Category-specific visual recognition as affected by aging and expertise.
AB  - The influence of aging and expertise on visual identification as function of
      semantic category (animals and tools) and spatial-frequency content of stimuli
      was investigated. Three-age groups of experts (whose profession required the use
      of manipulable tools) and non-experts, participated to the experiment. Data
      showed a different involvement of low and high spatial-frequency channels in
      processing objects semantically different: animals were identified at a coarse
      spatial scale (low spatial frequencies) and tools at a finer spatial scale
      (higher spatial frequencies). A gradual age-related decline in the identification
      for both categories (more physical information was required as the age increased)
      was found in non-experts, while in experts a similar trend was found only for
      animals and not for tools. In fact, independently on the age, experts could
      identify tools without requiring more visual details, probably for the benefits
      from their long-term experience with tools. Expertise, represented at higher
      levels of cognitive processing, might compensate the loss of lower levels of
      information processing due to aging.

PMID- 16274760
TI  - Direction, location, and size of shunt flow in congenital heart disease evaluated
      by ECG-gated multislice computed tomography.
AB  - OBJECTIVE: To demonstrate the utility of multislice computed tomography (MSCT) in
      the evaluation of direction, location, and size of shunt flow in congenital heart
      disease. BACKGROUND: Transthoracic and transesophageal echocardiography, magnetic
      resonance imaging, and conventional angiography has been used to evaluate
      congenital heart disease; however, some are invasive and some do not provide
      accurate information about the spatial relationship to other organs. METHODS:
      Three patients with typical presentation of ventricular septal defect, atrial
      septal defect, and patent ductus arteriosus were recruited. Enhanced MSCT (Light
      Speed Ultra 16, General Electric) was performed with a 1.25-mm slice thickness,
      helical pitch 3.25. Following intravenous injection of 100 ml of iodinated
      contrast material (350 mg I/ml) at a rate of 3 ml/s, CT scanning was performed
      with retrospective ECG-gated reconstruction at 5 s and 30 s after injection.
      RESULTS: In all cases the information of direction, location, and size of shunt
      flow including left-to-right and right-to-left shunt with spatial relationship to
      other organs could be obtained non-invasively. CONCLUSION: ECG-gated MSCT is a
      useful tool to evaluate congenital heart diseases with shunts.

PMID- 16274761
TI  - Introduction to animal antimicrobial use data collection in the United States:
      methodological options.

PMID- 16274762
TI  - The incorporation of SPECT functional lung imaging into inverse radiotherapy
      planning for non-small cell lung cancer.
AB  - BACKGROUND AND PURPOSE: Patients with non-small cell lung cancer (NSCLC) often
      have inhomogeneous lung perfusion. Radiotherapy planning computed tomography (CT)
      scans have been accurately co-registered with lung perfusion single photon
      emission computed tomography (SPECT) scans to design radiotherapy treatments
      which limit dose to healthy 'perfused' lung. PATIENTS AND METHODS: Patients with
      localised NSCLC had CT and SPECT scans accurately co-registered in the planning
      system. The SPECT images were used to define a volume of perfused 'functioning'
      lung (FL). Inverse planning software was used to create 3D-conformal plans, the
      planning objective being either to minimise the dose to whole lungs (WL) or to
      minimise the dose to FL. RESULTS: Four plans were created for each of six
      patients. The mean difference in volume between WL and FL was 1011.7 cm(3) (range
      596.2-1581.1cm(3)). One patient with bilateral upper lobe perfusion deficits had
      a 16% reduction in FLV(20) (the percentage volume of functioning lung receiving
      >or=20 Gy). The remaining patients had inhomogeneous perfusion deficits such that
      inverse planning was not able to sufficiently optimise beam angles to avoid
      functioning lung. CONCLUSION: SPECT perfusion images can be accurately co
      registered with radiotherapy planning CT scans and may be helpful in creating
      treatment plans for patients with large perfusion deficits.

PMID- 16274763
TI  - Spatial aspects of combined modality radiotherapy.
AB  - BACKGROUND AND PURPOSE: A combined modality radiotherapy (CMRT) incorporates both
      external beam radiotherapy (EBT) and targeted radionuclide therapy (TRT)
      components. The spatial aspects of this combination were explored by utilising
      intensity modulated radiotherapy (IMRT) to provide a non-uniform EBT dose
      distribution. PATIENTS AND METHODS: Three methods of prescribing the required non
      uniform distribution of EBT dose are described, based on both physical and
      biological criteria according to the distribution of TRT uptake. The results and
      consequences of these prescriptions are explored by application to three examples
      of patient data. RESULTS: The planning procedure adopted allowed IMRT plans to be
      produced that met the prescription requirements. However, when the treatment was
      planned as a CMRT, compared with the use of EBT alone, more satisfactory target
      doses could be achieved with lower doses to normal tissues. The effects of errors
      in EBT delivery and in the functional data were found to cause a non-uniform
      prescription to tend towards the uniform case. CONCLUSIONS: The methods and
      results are relevant for more general biological treatment planning, in which
      IMRT may be used to produce dose distributions prescribed according to tumour
      function. The effects of delivery and dose calculation errors can have a
      significant impact on how such treatments should be planned.

PMID- 16274764
TI  - Angiographic evaluation of the effect of intracoronary abciximab administration
      in patients undergoing urgent PCI.
AB  - BACKGROUND: Recent data suggest that the intracoronary (i.c.) administration of a
      systemic bolus dose of abciximab during PCI may increase the efficacy of this
      antiplatelet drug. However, the effect of i.c. abciximab on coronary angiographic
      flow has been not clarified. METHODS: We studied 37 consecutive patients with
      acute coronary syndromes (ACS) who underwent successful urgent PCI on the target
      vessel and were treated by an i.c. abciximab bolus (0.25 mg/kg) prior to the
      first balloon inflation (Group IC), and 37 matched controls who were treated by
      intravenous (i.v.) abciximab bolus at the same dose (Group IV). Corrected TIMI
      frame count (CTFC) in the culprit and in a non-culprit coronary artery branch was
      assessed before treatment, immediately after intracoronary administration of
      abciximab bolus and at the end of the procedure. RESULTS: After administration of
      abciximab, CTFC significantly decreased from 48+37 to 33+30 (P=0.001) in the
      culprit vessel while in the non-culprit vessel it remained unchanged (16+7 pre
      treatment and 16+7 post-treatment, P=0.68). Final CTFC was 12+4 in Group IC and
      14+5 in Group IV (P=0.069). Post-treatment mean peak of the cardiac enzymes
      showed a trend toward reduction in Group IC compared with Group IV. CONCLUSIONS:
      The i.c. administration of abciximab bolus acutely decreases CTFC through culprit
      vessels of patients with ACS undergoing urgent PCI. Further studies evaluating
      the potential clinical benefits associated with i.c. abciximab administration are
      warranted.

PMID- 16274765
TI  - Comparison of modified short axis view and apical four chamber view in evaluating
      right ventricular function after repair of tetralogy of Fallot.
AB  - BACKGROUND: In clinical settings an easy and reliable method for following up
      right ventricular (RV) function in patients after repair of tetralogy of Fallot
      (TOF) is needed. It is, however, unclear whether the novel modified short axis
      view from echocardiography is superior to the apical four chamber view in this
      aspect. MATERIALS AND METHODS: Thirty postoperative TOF patients with median age
      17 years (range 6-45 years) and follow up period of 10 years (range 0.5-40 years)
      were examined echocardiographically using the apical four chamber view and the
      novel modified short axis view. RV areas in end-systole (Amin) and end-diastole
      (Amax) were measured and an area fraction [(Amax - Amin)/Amax * 100%] was
      calculated from the respective view. RV ejection fraction was assessed through
      magnetic resonance imaging (MRI). The RV area fractions from echocardiography
      were compared to the RV ejection fraction. RESULTS: The right ventricular area
      fraction derived from the modified short axis view was significantly lower than
      that from the apical four chamber view (34.3+/-9.1% vs. 42.5+/-10.2%, p=0.007).
      Both the RV area fractions obtained from the modified short axis view (r=0.674,
      p<0.001) and from the apical four chamber view (r=0.512, p=0.025) correlated
      significantly with the MRI derived RV ejection fraction. CONCLUSION: The novel
      modified short axis view from echocardiography may be superior to the apical four
      chamber view for routine follow up of patients after TOF repair, in whom the
      right ventricular outflow tract plays an important role in the right ventricular
      systolic function.

PMID- 16274766
TI  - Ventricular fibrillation in acute myocardial infarction before and during primary
      PCI.
AB  - BACKGROUND: There are scarce and sometimes contradictory data about ventricular
      fibrillation (VF) during the acute phase of MI. In-hospital VF most often occurs
      with inferior MI, when treated with fibrinolytics. Out-of-hospital VF seems to be
      associated with anterior MI. We studied characteristics of patients with VF
      during reperfusion therapy by primary angioplasty (PCI) versus patients with VF
      before PCI. METHODS: From January 1995 until December 2001, we treated 2826
      patients for acute MI and reviewed clinical records of all patients who developed
      VF and classified the patients according to the first episode of VF: either
      before or during the angioplasty procedure. RESULTS: VF developed in 219 (8%)
      patients. Patients with VF during reperfusion therapy (n=74, 3%) were older
      (p=0.03), more frequently female (0.04), less often had heart failure (p=0.04),
      when compared with patient with VF before PCI (n=145, 5%). Patients with VF
      during PCI experienced more often preinfarction angina (p=0.009) and suffered
      more often from inferior MI (p=0.001), when compared with patients with VF before
      PCI. CONCLUSIONS: Patients with early VF before reperfusion have different
      characteristics when compared with patients with VF during reperfusion. Infarct
      location is a major determinant of timing of VF, when both groups are compared
      (p<0.001).

PMID- 16274767
TI  - Predictors of in-hospital mortality in patients with acute aortic dissection.
AB  - BACKGROUND: If acute aortic dissection is a highly lethal disease. There were few
      reports addressing predictors of in-hospital mortality of this disease in
      southern Taiwan. METHODS: If from January 1, 1989, to December 31, 2001, patients
      with acute aortic dissection were enrolled. Patient demographics, history,
      clinical characteristics, and laboratory examinations were reviewed. Univariate
      testing followed by logistic regression analysis was performed to identify the
      predictors of in-hospital mortality. RESULTS: If in total, 198 (146 male)
      patients with mean age of 60.7+/-11.6 years were enrolled. The in-hospital
      mortality rate was 34.8% in overall patients, 58.8% for type A dissection, and
      14.8% for type B dissection. There were five independent predictors of in
      hospital mortality: presence of hypertension [odds ratio (OR)=0.09, 95%
      confidence interval (CI)=0.02-0.36, p<0.001], type A dissection (OR=8.26, 95%
      CI=3.44-19.60, p<0.001), probable extravasation (pericardial effusion in type A
      dissection or left side pleural effusion in patients with involvement of
      descending thoracic aorta) (OR=2.70, 95% CI=1.14-6.41, p=0.024), visible intimal
      flap in ascending aorta in trans-thoracic echocardiography (OR=4.46, 95% CI=1.58
      12.60, p=0.005), and acute renal deterioration (OR=3.85, 95% CI=1.36-10.87,
      p=0.011). CONCLUSIONS: If acute aortic dissection, especially type A, is with
      high mortality in southern Taiwan. There are five independent predictors of in
      hospital mortality found in current analysis. Our result may remind doctors to
      find out their patients at high risk. Trans-thoracic echocardiography is a useful
      tool to find out patients at high risk because it is easily performed to check if
      there is pericardial effusion or visible intimal flap in ascending aorta.

PMID- 16274768
TI  - Mesenchymal stem cells participating in ex vivo endothelium repair and its effect
      on vascular smooth muscle cells growth.
AB  - BACKGROUND: Previous studies have shown that mesenchymal stem cells (MSCs)
      transplantation can promote neovascularization and regenerate damaged myocardium.
      However, it remains unknown whether MSCs seeding can be used to repair injured
      cellular components in vascular diseases. In this study we explored the
      feasibility of applying MSCs to endothelium repair in endothelial damage and
      vasoproliferative disorders. METHODS: Ex vivo model of endothelium repair was
      developed in which rabbit vascular smooth muscle cells (SMCs) were inoculated
      into the upper chamber and rabbit endothelial cells (ECs)/human MSCs into the
      lower chamber of a co-culture system. 3H-TdR incorporation and PCNA protein
      expression were assayed and migrated number of SMCs was calculated to evaluate
      the effect of MSCs seeding on SMCs growth. Flk-1 and vWF protein expressions were
      observed to analyze the plasticity of the seeded MSCs along endothelial lineage.
      RESULTS: In this co-culture system, no vWF protein but Flk-1 protein was observed
      in the 25.71% of MSCs after having been co-cultured with mature rabbit ECs for 5
      days. Compared with the control group, the proliferation and migration of SMCs
      was significantly increased by proliferative ECs but decreased by confluent ECs
      (n=6, P<0.01). MSCs seeding decreased the proliferation and migration of SMCs
      compatible with the effect of proliferative ECs (n=6, P<0.001). However, no
      inhibition on SMCs growth was observed with MSCs seeding in comparison to the
      effect of confluent ECs. CONCLUSIONS: MSCs seeding can inhibit the proliferation
      and migration of SMCs. MSCs co-cultured with mature ECs have the ability to
      undergo milieu-dependent differentiation toward ECs.

PMID- 16274769
TI  - Retrospective investigation of hospitalised patients with atrial fibrillation in
      mainland China.
AB  - OBJECTIVE: To evaluate the epidemiology and status of atrial fibrillation in
      China. METHODS: Retrospective analysis of hospital records of patients with a
      primary diagnosis of atrial fibrillation, discharged between January 1999 and
      December 2001. RESULTS: Data were analysed from 9297 patients (mean age 65.5
      years) from 41 hospitals in mainland China. During the period studied, atrial
      fibrillation admissions (mean 7.9%) increased as a proportion of cardiovascular
      admissions. The distribution of atrial fibrillation increased with age. Causes
      and associated conditions were advanced age (58.1%), hypertension (40.3%),
      coronary heart disease (34.8%), heart failure (33.1%), rheumatic valvular disease
      (23.9%), idiopathic atrial fibrillation (7.4%), cardiomyopathy (5.4%) and
      diabetes (4.1%). Permanent atrial fibrillation accounted for almost half of the
      patients (49.5%), and paroxysmal and persistent atrial fibrillation the remainder
      (33.7% and 16.7%, respectively). Paroxysmal atrial fibrillation was treated
      mainly by rhythm control (56.4%). In 82.8% of patients with chronic atrial
      fibrillation, a rate-control strategy was used. The prevalence of stroke was
      17.5%. In non-valvular atrial fibrillation, risk factors associated with stroke
      included advanced age, history of hypertension, coronary heart disease and type
      of atrial fibrillation. A total of 64.5% of patients received antithrombotic
      therapy, predominantly with antiplatelet agents. Patients managed with
      antiplatelet or anticoagulant drugs had a significantly lower stroke rate than
      those receiving neither treatment, but there was no significant difference
      between antiplatelet and anticoagulant agents. CONCLUSION: Most of the atrial
      fibrillation-related epidemiological factors in this population were similar to
      those reported in other countries. Antiplatelet and anticoagulant treatment both
      reduced stroke rate significantly.

PMID- 16274770
TI  - Relationships between weather and myocardial infarction: a biometeorological
      approach.
AB  - OBJECTIVES: To calculate threshold values of weather discomfort which increase
      the risk of hospital admissions for myocardial infarction in winter and summer.
      BACKGROUND: Notwithstanding heat waves were reported to acutely increase hospital
      admissions for cardiovascular diseases, large surveys failed to reveal any
      increase of event rates with increasing air temperature. However, the assessment
      of air temperature does not allow evaluation of the actual discomfort perception
      caused by the combination of different meteorological parameters. METHODS:
      Hospital admissions for myocardial infarction for the period 1998-2002 in
      Florence, Italy, were considered. The percentages of variation of daily event
      rates according to daily mean air temperature variations were preliminary derived
      by using a regression analysis. An alternative biometeorological approach,
      considering the Apparent Temperature Index (ATI) in summer, and the New
      U.S./Canada Wind Chill Temperature Index (NWCTI) in winter, which combine air
      temperature, relative humidity and wind velocity, was then used. RESULTS: The
      traditional approach showed that daily event rates significantly increased with
      daily mean air temperature decrease (10 degrees C decrease were associated with
      19% increase in daily event rates for people older than 65 years), but failed to
      show any negative effect caused by hot climatic conditions. Conversely the
      biometeorological approach allowed to show that at least 9 h per day of severe
      discomfort caused by hot conditions significantly increased the rate of admission
      (P<0.01). CONCLUSIONS: This approach might be useful for the development of an
      operative weather watch/warning system for population and for hospital
      professional care.

PMID- 16274771
TI  - Activity questionnaires; a useful tool in accessing heart failure patients.
AB  - AIM: The aim of the study was to correlate the score derived from Specific
      Activity Questionnaire (SAQ), Left Ventricular Dysfunction 36 (LVD 36) and the
      Minnesota Living with Heart Failure Questionnaire (LIhFE) with peak oxygen
      consumption measured during maximal treadmill exercise spirometry in patients
      with heart failure. METHODS: We prospectively studied 106 patients, average age
      47+/-15.5 (mean+/-SD), with symptomatic heart failure. All were asked to answer
      the questions of the above mentioned questionnaires. Subsequently patients
      underwent treadmill exercise spirometry to measure peak oxygen consumption (VO2
      peak ml/kg/min) using the Dargie protocol and to derive functional class
      according to the Weber classification system. RESULTS: SAQ had a very high
      performance in classifying patients with a VO2 peak <20 ml/kg/min and those with
      a VO2 peak <14 ml/kg/min. The correlation between VO2 peak achieved and the METs
      corresponding to the score derived from SAQ according to the given answers was
      r=0.77 (p<0.01). The correlation between VO2 peak achieved and the score from LVD
      36 was r=-0.74 (p<0.01). The correlation between VO2 peak achieved and the score
      from LIhFE was r=-0.71 (p<0.01). CONCLUSION: The Specific Activity Questionnaire,
      the Left Ventricular Dysfunction and the Minnesota Living with Heart Failure
      Questionnaire were used to predict aerobic capacity and all correlated
      significantly with peak VO2 achieved from exercise spirometry. The above
      questionnaires represent a useful method to access heart failure patients and are
      valuable for those unable to undergo a treadmill test.

PMID- 16274772
TI  - Initial clinical experience of real-time three-dimensional echocardiography in
      neonates with isolated congenital ductus arteriosus aneurysm.
AB  - BACKGROUND: Congenital ductus arteriosus aneurysm (DAA) was considered rare but
      potentially fatal abnormality, often followed by surgical intervention after
      careful evaluation. This prospective study used real-time three-dimensional
      echocardiography (RT3DE) to assist in evaluation of neonatal DAA. METHODS: A
      total of 1390 full-term neonates were enrolled in this study between 2002 and
      2003. They received two-dimensional echocardiographic (2DE) screening and
      periodic follow-up. RT3DE was performed selectively for newborns with DAA.
      RESULTS: DAA were detected in 116 (8.34%) newborns using 2DE. Maximum diameter of
      the DAAs ranged from 6.8 to 14.0 mm (8.2+/-1.1 mm). None of the cases were
      symptomatic or had complications related to DAA. There were no significant
      differences in sex and gestational age between the newborns with and without DAA.
      Neonates with DAA had a higher birth body weight and a higher incidence of large
      for-gestational-age (P<0.05). RT3DE provided instant, consistent and reliable 3D
      images of DAA and its related structures and allowed for more rapid examination
      times and reduction of baby wait times. CONCLUSIONS: Congenital DAA is as common
      as has been previously reported. RT3DE is useful in assisting evaluation of DAA.
      Preferred images of DAA were typically visualized in the high parasternal short
      axis view before the third day of life. Routine use of RT3DE is suggested to
      enhance assessment of neonates with DAA detected by 2DE.

PMID- 16274773
TI  - Real time three-dimensional echocardiography moves towards clinically useful
      neonatal cardiovascular imaging.

PMID- 16274774
TI  - ACE-DD genotype is associated with the occurrence of acute coronary syndrome in
      postmenopausal women.
AB  - The insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme
      (ACE), the A1166C polymorphism in the angiotensin type 1 receptor (AT1R), and the
      M235T polymorphism of the angiotensinogen gene are associated with cardiovascular
      disease mostly in men. Few data are available on the effects of these genetic
      variations in postmenopausal women according to hormone replacement therapy (HRT)
      use. In this case-control study, we determine the frequency of mutant alleles in
      the ACE I/D, M235T and A1166C polymorphisms in postmenopausal Caucasian women
      with and without a diagnosis of acute coronary syndrome (ACS). Data from 198
      women with ACS (63+/-10 years) and 149 controls (62+/-7 years) showed that ACE-DD
      genotype was more prevalent in women with ACS compared to controls (30% vs. 19%,
      P<0.05). There was no difference in genotype distributions for either the M235T
      or the A1166C polymorphisms between groups. The difference in ACE genotype
      distribution between ACS women and controls was driven by current HRT users with
      30% of ACS and 15% of controls carrying the ACE-DD genotype (P<0.05). The
      oligenic combination of ACE-DD and M235T-TT genotypes was higher in ACS compared
      to controls. Among carriers of M235T-TT, 7% of ACS and 1% of controls also had
      the ACE-DD genotype, P<0.05. Thus, the ACE-DD genotype may be associated with ACS
      in postmenopausal women, particularly in HRT users.

PMID- 16274775
TI  - Diabetes mellitus is a strong, independent risk for atrial fibrillation and
      flutter in addition to other cardiovascular disease.
AB  - BACKGROUND: Diabetes mellitus (DM) is a major risk factor for atherosclerosis.
      There is a controversy in literature about correlation between DM and atrial
      fibrillation. The goal of this study was to evaluate DM as a risk factor for
      atrial fibrillation or flutter using a very large database. METHOD: Patient
      treatment files (PTF) containing discharge diagnoses were utilized using ICD-9
      codes of inpatient treatment from Veterans Health Administration Hospitals (VAH).
      Patients with type II DM (ICD-9 code 250.0) (293,124) discharged from the VAH
      between 1990 and 2000. Non-matched controls without DM but with hypertension
      (552,624) were selected from the same PTF. By using multi-variate logistic
      regressions, the occurrence of atrial fibrillation, atrial flutter, CHF, CAD and
      LVH was compared. RESULTS: Atrial fibrillations occurred in 43,674 (14.9%) DM
      patients vs. 57,077 (10.3%) in the control group (p<0.0001). Atrial flutter
      occurred in 11,852 (4%) of DM patients vs. 13,554 (2.5%) of the control group
      (p<0.0001). Using multi-variant analysis, DM remained independently associated
      with atrial fibrillation with an OR of 2.13, (95% CI: 2.10 to 2.16; p<0.0001) and
      flutter (OR 2.20, CI: 2.15 to 2.26; p<0.0001). Furthermore, CHF (OR 3.12, CI:
      3.09 to 3.16; p<0.0001), LVH (OR 1.85, CI: 1.77 to 1.92; p<0.0001) and CAD (OR
      2.39, CI: 2.34 to 2.44; p<0.0001) were also independently associated with DM.
      CONCLUSION: This is the first large-scale study finding DM as a strong,
      independent risk for the occurrence of atrial fibrillation and flutter and other
      cardiovascular disease.

PMID- 16274776
TI  - Diabetes mellitus and atrial fibrillation: perspectives on epidemiological and
      pathophysiological links.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, which
      is also associated with a substantial risk of mortality and morbidity from
      stroke, thromboembolism, heart failure and hospitalisations. On a epidemiological
      basis, diabetes mellitus is commonly associated with AF. Nonetheless, AF is also
      associated with vascular disease and hypertension, which are themselves
      intimately linked to diabetes. Indeed, the precise pathophysiological and
      clinical relationships between AF and diabetes mellitus are not completely
      understood. What we do know is that both diabetes and AF are individually bad for
      our patients, and the presence of both requires aggressive management strategies.

PMID- 16274777
TI  - Adenosine prevents neutrophil adhesion to human endothelial cells after
      hypoxia/reoxygenation.
AB  - BACKGROUND: Neutrophil adhesion to vascular endothelium has been implicated in
      the pathogenesis of myocardial injury after ischaemia/reperfusion (IR) and the
      "no-reflow" phenomenon. Adenosine and sodium-nitroprusside (SNP) have been used
      clinically to ameliorate this injury. We set out to establish a human cellular
      model for the study of IR and to evaluate the effects of adenosine and SNP on
      neutrophil adhesion in vitro. METHODS: Cultured human umbilical vein endothelial
      cells (HUVEC) were exposed to hypoxia (5% CO2, 95% N2) or normoxia (room air, 5%
      CO2) for 2 h, followed by reoxygenation for 30 min (IR condition). Human
      neutrophils were then added together with adenosine (50 microM), SNP (10 microM)
      or no additive (control). After incubation for 1 h, neutrophil adhesion to
      endothelial cells was quantified via automated cell counts. The experiment was
      repeated with the adenosine treatment alone, with and without the addition of the
      adenosine A2A receptor blocker ZM-241385. RESULTS: Compared with baseline
      neutrophil adhesion after normoxia, hypoxia followed by reoxygenation increased
      adhesion to 189+/-43% (p=0.01), but this effect was prevented by the addition of
      adenosine (109+/-17%, p=NS compared to control conditions). SNP did not affect
      the increased adhesion caused by hypoxia (166+/-25%, p=NS). The addition of ZM
      241385 did not inhibit the effect of adenosine on neutrophil adhesion after
      hypoxia/reoxygenation. CONCLUSIONS: Exposure of human endothelial cells to
      hypoxia/reoxygenation causes increased neutrophil adhesion. This effect is
      prevented by adenosine, but not mediated by the A2A receptor. SNP does not
      prevent neutrophil adhesion after IR in vitro.

PMID- 16274778
TI  - Positive correlations between serum calcineurin activity and left ventricular
      hypertrophy.
AB  - BACKGROUND: Among various intracellular signaling cascades associated with
      cardiac hypertrophy, the involvement of calcineurin (CaN; Ca2+-calmodulin
      dependent protein phosphatase) is gaining credence because of its enhanced
      activity in ventricular myocardium and the ability of CaN inhibitors to prevent
      pressure-overload hypertrophy. Since our recent findings attribute clinical
      significance to serum CaN, the present investigation was conducted to evaluate
      its significance in cardiac hypertrophy. METHODS: The study group comprised of
      patients diagnosed for hypertensive hypertrophy, hypertrophic cardiomyopathy,
      chronic coronary artery disease with compensatory left ventricular hypertrophy,
      dilated cardiomyopathy and acute myocardial infarction. Serum contents of CaN and
      calmodulin were determined and activities of CaN as well as of acid and alkaline
      phosphatases were assayed and correlated with 2D echocardiography findings. The
      results were compared with those obtained from age-matched healthy volunteers.
      RESULTS: Serum CaN activity, but not of acid or alkaline phosphatases, was
      significantly enhanced by 2-fold in hypertensive hypertrophy, 3-fold in
      hypertrophic cardiomyopathy and 3.75-fold in chronic coronary artery disease
      associated with left ventricular hypertrophy, unaccompanied by changes in serum
      contents of calmodulin and CaN. No such increases were observed in acute
      myocardial infarction and dilated cardiomyopathy. CONCLUSIONS: Positive
      correlations observed between serum CaN activity and enhanced left ventricular
      mass in cardiac hypertrophy suggest that assaying serum CaN activity may be
      useful in the diagnosis and management of left ventricular hypertrophy.

PMID- 16274779
TI  - Rising cholesterol levels in China.

PMID- 16274780
TI  - Clinical perspectives of the primary spontaneous coronary artery dissection.
AB  - Spontaneous coronary artery dissection is a rare cause of acute coronary syndrome
      or sudden death. Typically it affects young women during the peripartum period
      and those using oral contraceptives. The pathophysiology remains unclear, but an
      eosinophilic periadventitial inflammation has been commonly observed in such
      cases. Unlike atherosclerotic intimal dissection, the dissection plane in the
      spontaneous dissection lies within the media or between the media and adventitia.
      Due to the rarity of the condition, the optimal management of the spontaneous
      coronary artery dissection has not been established and it may range from
      conservative medical treatment to percutaneous or surgical interventions
      depending upon the anatomy of the dissection, compromise of the vessel lumen and
      the clinical circumstances. The reported prognosis varies widely. Spontaneous
      coronary artery dissection should be considered in the differential diagnosis in
      young persons with precordial chest pain, especially women in the peripartum
      state and those using oral contraceptives. The clinical perspectives of the
      primary spontaneous coronary artery dissection are elaborated.

PMID- 16274781
TI  - B-type natriuretic peptide and N-terminal pro brain natriuretic peptide are
      related to systolic and diastolic left ventricular function assessed by
      radionuclide ventriculography.

PMID- 16274782
TI  - Sinus of valsalva aneurysm dissecting into ventricular septum.

PMID- 16274783
TI  - Recovery of acute myocarditis with biventricular assist device in infant.
AB  - A 5-month-old boy was admitted to hospital presenting with cardiogenic shock. The
      echocardiographic examinations revealed a severe ventricular dysfunction. Despite
      the aggressive medical therapy, his hemodynamic status progressively
      deteriorated. Mechanical circulatory support was initially provided with
      extracorporeal membrane oxygenation (ECMO). Because his hemodynamic condition had
      not improved, the ECMO was removed and a biventricular assist device (BVAD) was
      instituted. After 10 days, the ventricular function had recovered and the BVAD
      could be removed. This report describes a successful bridge to recovery using a
      BVAD in an infant suffering from acute myocarditis.

PMID- 16274784
TI  - Focal myocardial fibrosis and edema in acute myocarditis demonstrated by
      multislice computed tomography.

PMID- 16274787
TI  - Informed consent in otolaryngology research.

PMID- 16274786
TI  - EEG correlates of multimodal ganzfeld induced hallucinatory imagery.
AB  - Multimodal ganzfeld (MMGF) frequently induces dreamlike, pseudo-hallucinatory
      imagery. The aim of the study was to explore EEG correlates of MMGF-induced
      imagery. In a screening phase, seven 'high-responders' were selected by frequency
      and quality of their reported hallucinatory experience in MMGF. Each of these
      subjects then participated in three MMGF sessions (45 min) with simultaneous 19
      channel EEG recordings and indicated occurrences of imagery by pressing a button.
      Relative spectral power changes during percept formation (30 s preceding
      subjects' reports) with respect to intra-individual baselines (no-imagery EEG)
      were analysed. At the beginning of the 30-s 'image formation' period alpha was
      slightly reduced than in the 'no-imagery' periods. This was followed by increased
      power in the higher alpha frequency band (10-12 Hz) which then declined in a
      monotonic fashion. This decline in higher alpha power was accompanied by
      increased power in the beta frequency bands. Throughout the image formation
      period there was a steady decline in power of low frequency alpha (8-10 Hz).
      Correlations between descriptors of subjective experience and EEG power changes
      were evaluated in terms of their global average magnitude and variability in
      time. Results indicate that the acceleration of alpha activity is a nonspecific
      effect of MMGF. In contrast, the tri-phasic profile of faster alpha activity
      seems to be a specific correlate of the retrieval and transformation of memory
      content in ganzfeld imagery.

PMID- 16274788
TI  - Common movement disorders affecting the larynx: a report from the
      neurolaryngology committee of the AAO-HNS.
AB  - Laryngeal physiology depends on dynamic neuromuscular forces acting on a basic
      framework of cartilage and specialized soft tissues, that is, the vocal folds. A
      working understanding of this organ in health and disease requires knowledge of
      specific neurological processes that may affect voice, swallowing, and airway
      regulation. Neuromuscular impairment continues to be a dominant topic in the
      study of laryngeal disorders. This subcommittee presentation reviews important
      aspects of the neurolaryngeal history and physical examination. After this
      foundation, 4 common movement disorders affecting the larynx are covered in
      separate subsections. These are stroke, Parkinson's disease, laryngeal tremor,
      and spasmodic dysphonia. State-of-the-art reviews reflecting our understanding of
      these clinical issues are presented in this summary.

PMID- 16274789
TI  - Histopathologic effects of cidofovir on cartilage.
AB  - OBJECTIVE: To evaluate the effects of subcutaneously injected cidofovir on
      cartilage in a rabbit model. STUDY DESIGN: Prospective study. The ears of 6 New
      Zealand White rabbits received perichondrial injection at 2 sites each of 0.1 mL
      of cidofovir in concentrations of 75 mg/mL, 25 mg/mL, 5 mg/mL, and 0 mg/mL.
      Animals were monitored for 6 weeks, and then injection sites excised and
      evaluated for histopathologic changes in epithelium, perichondrium, and
      cartilage. RESULTS: A positive dose-response relationship existed for gross skin
      changes; however, there was no dose-response relationship for severity of change
      in the epithelium. There was a temporal component to gross changes, demonstrating
      peak incidence and severity between 2 and 3 weeks after injection, with
      resolution of most changes within the 6-week study period. There was an increased
      likelihood of cartilage change when injecting cidofovir, but no clear
      relationship with injected dose. CONCLUSION: We report the first evaluation of
      the local effects of cidofovir injection on cartilage. The results of this study
      using a rabbit model suggest that delayed skin changes or histopathologic change
      in the cartilage may be expected in approximately one third of sites injected.
      Although there was a statistical likelihood for increased local change after
      cidofovir injection, there was no correlation of severity with injected dose.
      SIGNIFICANCE: Higher doses of cidofovir than commonly are used in the treatment
      of recurrent respiratory papillomatosis may be safe to use, although the effects
      of repeat application and long-term complications are not yet evident. EBM
      RATING: B-2.

PMID- 16274790
TI  - Mitomycin C effect on fibrous adhesions of rabbit temporomandibular joint.
AB  - OBJECTIVE: To evaluate influence of mitomycin C on fibrosis in temporomandibular
      joints of rabbits with mandibular traction. STUDY DESIGN: Twenty rabbits (8
      control, 12 mitomycin C group) were included. Titanium screws were placed in the
      anterior edge of the right masseter tuberosity and the posterior part of the
      right zygoma. Elastic bands were placed between 2 screws to initiate posterio
      superior displacement of the mandible to the right. Animals in the control group
      (CG) received intraarticular NaCl (0.9%) on the nondrawing (left) side, and
      animals in the study group (SG) received mitomycin C weekly (0.4 mg/mL) for 6
      weeks. Rabbits were decapitated, temporomandibular joints were removed, and
      histopathological investigation was performed. RESULTS: Microscopically, 4 of 6
      rabbits in the CG had fibrosis in the temporomandibular joint, whereas only 1 of
      11 rabbits in the SG had fibrosis (P < 0.05). CONCLUSION: Application of
      mitomycin C to the temporomandibular joint of rabbits significantly reduces
      formation of intraarticular fibrous adhesions. SIGNIFICANCE: This is the first
      study in the literature investigating the use of mitomycin C in the joints. EBM
      RATING: B-2.

PMID- 16274791
TI  - Short hospital stay after neck dissection.
AB  - OBJECTIVE: Cervical lymphadenectomy is a common adjunctive therapy for the
      treatment of head and neck malignancies. Postoperative care of otherwise healthy
      patients with isolated neck dissection or in combination with other procedures
      often requires limited nursing attention after the first postoperative day. At
      our institution, patients are often taught to manage their drains and discharged
      home. Therefore, we sought to characterize the subset of patients who will
      require only overnight hospital care after neck dissection. STUDY DESIGN: We
      retrospectively reviewed our experience in a tertiary academic medical center
      over the past 6 years with patients who underwent neck dissection, isolated or
      with other procedures, and were sent home by postoperative day 1. RESULTS: In
      all, 23 of 260 patients were identified (8.8%). Two patients were noted to have
      postoperative seromas, with no other complications noted. CONCLUSION: We conclude
      that short hospital stay after neck dissection is reasonable for the motivated
      patient without significant comorbidities. SIGNIFICANCE: This is the first study
      to examine the feasibility of short hospital stay after neck dissection. EBM
      RATING: C.

PMID- 16274792
TI  - Voice restoration with the advantage tracheoesophageal voice prosthesis.
AB  - OBJECTIVES: To determine whether the Blom-Singer indwelling Advantage
      tracheoesophageal voice prosthesis (TEP) extends prosthesis life span
      significantly in patients with documented premature device failure due to fungal
      colonization. STUDY DESIGN AND SETTING: Data were collected in a prospective
      manner on a total of 42 standard indwelling TEP users who exhibited early device
      failure, that is, between 2 weeks and 6 months, due to fungal colonization of the
      flap valve despite appropriate use of oral antifungal agents. There were 29 men
      and 13 women, whose ages ranged from 36 years 10 months to 86 years 8 months.
      METHODS: Baseline data were derived from the average number of days 3 previous
      standard indwelling prostheses functioned before leaking. An Advantage indwelling
      TEP was placed after the third change, oral antifungal agents stopped, and
      routine care implemented, that is, flush and brush the device in situ twice each
      day. Each participant was assigned to 1 of 3 groups. Group 1 had device failure
      equal to or less than 2 months (n = 12). Group 2 had device failure between 2 and
      4 months (n = 19). Group 3 had device failure between 4 and 6 months (n = 11).
      RESULTS: Groups 1 and 2 exhibited significantly longer device life span, that is,
      77 and 82 days, respectively (P < 0.01), and group 3 exhibited device life span
      that was longer but not significantly so, that is, 12 days (P > 0.05), after the
      change from standard to Advantage TEP. Individual data indicated that the
      majority of participants, that is, 32 of 42 (76.2%), experienced longer device
      life span after changing to the Advantage prosthesis. Specifically, 9 of 12
      (75.0%) users in group 1, 17 of 19 (89.5%) users in group 2, and 6 of 11 (54.5%)
      users in group 3 exhibited longer device life span. The combination of using an
      Advantage TEP, discontinuing oral antifungal agents, and reducing the number of
      both TEP changes and clinic visits resulted in overall cost benefits for both the
      user and the health care system. The cost benefit for group 1 was dollar 520.00;
      group 2, dollar 393.00; and group 3, dollar 204.25. CONCLUSIONS: The Advantage
      TEP extended device life span significantly for standard indwelling device users
      with documented premature device failure due to fungal colonization, reduced
      costs associated with tracheoesophageal voice restoration rehabilitation, and
      enhanced user satisfaction by eliminating use of oral antifungal agents and
      reducing clinic visits. SIGNIFICANCE: Use of an Advantage indwelling voice
      prosthesis is warranted from both cost and user satisfaction perspectives when
      early and repeated device failure occurs as a result of fungal colonization. EBM
      RATING: B-3.

PMID- 16274793
TI  - Quality of life in prosthetic voice users.
AB  - OBJECTIVE: This study was designed to measure the efficacy of prosthetic voice
      restoration for laryngectomees in relation to various quality-of-life parameters.
      STUDY DESIGN AND SETTING: The University of Washington Quality of Life Scale, the
      Functional Assessment of Cancer Therapy Scale, and a demographic data form of our
      own design were completed by 16 laryngectomees who had undergone prosthetic voice
      restoration in our private practice by Blom-Singer methodology. RESULTS: More
      than 80% of the respondents were positive in their assessment of each category on
      all three surveys. CONCLUSION: Prosthetic voice restoration in private practice
      resulted in achieved expectations, satisfaction with speech, and good quality of
      life as measured by physical, functional, social, and emotional well-being
      parameters. SIGNIFICANCE: Laryngectomees may be offered prosthetic voice
      restoration with a high likelihood that they will be satisfied. EBM RATING: C.

PMID- 16274794
TI  - Postlaryngectomy pharyngocutaneous fistula: incidence, predisposing factors, and
      therapy.
AB  - OBJECTIVE: The pharyngocutaneous fistula (PCF) is a serious complication after
      total laryngectomy, and its etiology is not well understood yet. The aim of our
      study was to evaluate predisposing factors, incidence, and management of this
      complication. STUDY DESIGN AND SETTING: This was a retrospective study of 268
      patients who underwent total laryngectomy in our clinic (January 1990-December
      2001). A number of factors potentially predisposing to PCF formation were
      evaluated. RESULTS: A PCF was observed in 16% of patients. Systemic diseases,
      previous radiotherapy, supraglottic origin of tumor, and concurrent radical neck
      dissection were significantly associated with PCF. Spontaneous closure was noted
      in 28 patients, whereas a surgical closure was necessary in 15 patients.
      CONCLUSIONS: In presence of a specific risk factor, PCF can be expected;
      nevertheless, its prevention remains very difficult. Moreover, given the high
      percentage of spontaneous closure, we suggest the "wait and see" approach for 28
      days before proceeding with a surgical approach. EBM RATING: C.

PMID- 16274795
TI  - PPAR activation and decreased proliferation in oral carcinoma cells with 4-HPR.
AB  - OBJECTIVE: To explore whether the mechanism of action of 4
      hydroxyphenylretinamide (4-HPR, fenretidine), a synthetic retinoid, involves the
      functional activation of the nuclear hormone receptor class known as PPARs
      (peroxisome proliferator-activated receptors). Also, to examine whether anti
      proliferative effects of this agent in head and neck cancer cells occur at
      biologically relevant concentrations. STUDY DESIGN/METHODS: CA 9-22, NA, and UM
      SCC 11B cells were treated with 4-HPR during their log phase growth and
      functional activation of PPAR gamma was evaluated by plate luminometry. Cellular
      proliferation was analyzed by standard MTT cell proliferation assays and cell
      counting. Student's t tests were performed for all experiments. RESULTS:
      Significant dose-dependent increases in PPAR gamma activation occurred in
      response to 4-HPR treatment. Proliferation was significantly inhibited by 4-HPR
      in a dose-dependent manner as judged by MTT and cell counting assays. These
      effects occurred at equimolar concentrations in both types of experiments within
      a range of clinically achievable doses (1-4 microM) of 4-HPR. CONCLUSIONS: 4-HPR
      can functionally activate PPAR gamma at clinically achievable doses. Decreased
      cancer cell proliferation secondary to PPAR gamma activation has been observed in
      other malignancies as well as upper aerodigestive cancer. PPAR gamma activation
      by 4-HPR represents another potential anti-cancer mechanism of action for this
      drug. CLINICAL SIGNIFICANCE: PPAR gamma activation represents a novel target for
      anti-cancer therapy for head and neck cancer and the current level of clinical
      toxicity of 4-HPR would be judged acceptable to utilize this agent alone or in
      combination chemotherapy.

PMID- 16274796
TI  - Clinical prognostic factors in malignant parotid gland tumors.
AB  - OBJECTIVE: To analyze the factors in parotid malignant epithelial tumors
      influencing recurrences and disease-specific survival. METHODS: We
      retrospectively reviewed the files of 150 patients treated at our institution,
      from 1974 to 1998. Twenty-four patients were not treated by surgery and were
      excluded from this study. The remaining 126 patients were treated with surgery
      and 74 patients had postoperative radiotherapy. Thirty-three patients were
      treated with parotidectomy plus neck dissection. Neck lymph node metastasis was
      found in 22 patients, 5 patients had occult neck metastasis, and 4 periparotid
      lymph nodes metastasis. The mean age was 49 years old. According to the UICC/1997
      TNM Classification, 49 patients were stage I, 27 stage II, 22 stage III, and 28
      stage IV. The influence of selected factors on the 10 year disease-specific
      survival was analyzed using the Kaplan-Meier actuarial method and the log-rank
      test. RESULTS: Forty patients had mucoepidermoid carcinoma, 18 patients
      adenocarcinoma NOS, 18 patients acinic cell carcinoma, 15 patients adenoid cystic
      carcinoma, 11 patients malignant mixed tumor, 11 patients salivary duct
      carcinoma, and 13 patients other pathology. Twenty-five patients had recurrences:
      17 had local recurrences, 4 patients had neck recurrences, and 4 were loco
      regional recurrences. Five factors influenced negatively the prognosis: 1) T
      stage (p.00001), 2) grade (p.00001), 3) + lymph nodes (p.0007), 4) facial nerve
      dysfunction (p.0001), and 5) age (p.004). Patients with high-grade tumors and
      high-stage tumors had the worst prognosis according to the multivariate analysis.
      The 10-year disease-specific survival was 97% for stage I, 81% for stage II, 56%
      for stage III, and 20% for stage IV. CONCLUSION: The grade of the tumor and stage
      were the most important prognostic factor. EBM RATING: C.

PMID- 16274797
TI  - Spectrum and management of deep neck space infections: an 8-year experience of
      234 cases.
AB  - OBJECTIVE: To study the clinical course and outcome of deep neck infections
      (DNI), with special emphasis on microbiology and histopathology. STUDY DESIGN:
      Two hundred thirty-four patients with DNIs were included in this study. Patients
      with peritonsillar or dental infections, infections arising from salivary glands,
      as well as subjects with abscesses caused by neck trauma were excluded. METHODS:
      Clinical analysis of all patients with DNIs who were treated between January 1,
      1997 and May 31, 2005 in a single center. RESULTS: In 13 patients, the DNI was
      the first manifestation of a malignant tumor. In 17 cases, the DNI was associated
      with cat-scratch disease (CSD). Six patients suffered from tuberculosis, and in
      another 7, an infected lateral cleft cyst was found. In 176 patients, the origin
      of DNI remained unclear. CONCLUSIONS: Our results demonstrate that CSD,
      tuberculosis, and malignant tumors must be considered as possible causes of DNIs.
      The current study represents one of the largest series of DNIs in the modern
      medical literature. EBM RATING: C.

PMID- 16274798
TI  - Dentigerous cysts presenting as head and neck infections.
AB  - OBJECTIVE: To describe dentigerous cysts presenting as head and neck infections.
      STUDY DESIGN AND SETTING: Retrospective analysis of 327 charts with an admitting
      diagnosis of head and neck infection, deep neck space infection, and dentigerous
      cysts treated at a tertiary care hospital between 1975 and 2004. RESULTS: Seven
      patients were identified who had dentigerous cysts that presented as head and
      neck infections. Six of these patients had recurrent infections at the same site
      and one was diagnosed with a submasseteric space abscess. The incidence of head
      and neck infections with dentigerous cysts as the underlying causative pathology
      was 2.1%. CONCLUSION: Head and neck infections with dentigerous cysts as
      underlying pathology are more common than perceived. SIGNIFICANCE: Typically not
      considered as sources of infection, dentigerous cysts must be considered in cases
      of head and neck infection. EBM RATING: C.

PMID- 16274799
TI  - Proton pump (H+/K+-ATPase) expression in human laryngeal seromucinous glands.
AB  - OBJECTIVE: Recent pilot research suggested that the H+/K+-ATPase (proton pump),
      which is the target of pharmacotherapy for laryngopharyngeal reflux disease
      (LPRD), is associated with human laryngeal submucosal glands. The hypothesis of
      this study is that proton pump is expressed in the human larynx, and is not
      solely associated with the parietal cells of the stomach. METHODS: Fifteen
      surgical larynx subjects (27 pathologic specimens) containing seromucinous glands
      from banked tissue were retrospectively obtained after approval from Human
      Subjects Committee. Banked human stomach tissue was also obtained for comparative
      positive and negative controls. Sections were immunostained with two monoclonal
      antibodies selectively reactive with alpha or beta subunits of the H+/K+-ATPase
      (proton) pump. RESULTS: In the human larynx, positive staining was seen in 14 of
      15 subjects. Twenty-six specimens showed consistent staining in the seromucinous
      cells and ducts for the alpha subunit, and 23 specimens for the beta subunit.
      Stomach parietal cells exhibited strongly positive staining for both the alpha
      and beta subunits of the proton pump. There was no staining in stomach cells that
      were not morphologically consistent with the parietal cell. CONCLUSION: The H+/K+
      ATPase (proton) pump is present in seromucinous cells and ducts in the human
      larynx, with some variable expression noted. Proton pump involvement in human
      laryngeal seromucinous glands may explain heightened laryngeal sensitivity in
      those patients with chronic laryngitis believed to have LPRD. Also, proton pump
      inhibitor pharmacotherapy may have a site of action in the human larynx,
      explaining some of the controversies attributable to LPRD. EBM RATING: B-3.

PMID- 16274800
TI  - The use of the Ligasure Vessel Sealing System in parotid gland surgery.
AB  - OBJECTIVE: To evaluate the role of the Ligasuretrade mark Vessel Sealing System
      (LVSS; Valleylab, Boulder, CO) in parotid surgery. STUDY DESIGN: A prospective
      study was conducted on 12 consecutive patients undergoing superficial
      parotidectomy, performed by using the LVSS device as the primary means of
      ligation. Inclusion criteria included parotid mass with no preoperative suspicion
      of malignancy, and no extension to the deep lobe of the parotid gland. Efficacy
      of hemostasis, cut-closure time, and postoperative complications were assessed.
      Results were compared with a historical control group, including cases on which
      the LVSS was not available. RESULTS: LVSS proved effective in providing ligation
      and hemostasis. There was a mean time gain of 52 minutes, compared with our
      historical control group. No postoperative bleeding, seroma, salivary fistula, or
      Frey syndrome were observed. One case of transient facial weakness occurred,
      which was completely resolved within 6 months. CONCLUSION: LVSS is a safe device
      for parotid gland surgery, providing sufficient hemostasis and reducing operative
      time. EBM RATING: B-2.

PMID- 16274801
TI  - Hemorrhage risk after quinsy tonsillectomy.
AB  - BACKGROUND: The goal of the study was to evaluate the incidence and possible
      predictive factors of post-tonsillectomy hemorrhage (PTH) in patients with
      peritonsillar abscess, treated by acute abscess tonsillectomy. METHODS: A
      retrospective cohort study was performed on 205 patients who underwent bilateral
      abscess tonsillectomy under general anesthesia. Age, sex, smoking habits, history
      of recurrent tonsillitis or prior peritonsillar abscess, current medical
      treatment, side of the peritonsillar abscess, initial treatment, surgeon's
      experience, procedure duration, intra- and postoperative anti-inflammatory
      medications, and side of bleeding were analyzed. RESULTS: Bleeding occurred in 27
      patients (13%). Ipsilateral hemorrhage was observed in 8 patients (4%) and
      contralateral hemorrhage in 19 patients (9%). The higher incidence of PTH in the
      side contralateral to the abscess was found to be statistically significant (P =
      0.02). Male gender (P = 0.042), smoking (P = 0.009), and aspirin intake (P =
      0.008) were statistically significant factors associated with an increased PTH
      risk. CONCLUSION: The risk of bleeding following abscess tonsillectomy seems
      higher than reported in elective tonsillectomy. This high incidence is mainly due
      to patients with prior aspirin intake or to bleeding in the side contralateral to
      the abscess. Postoperative bleeding could be reduced by performing a unilateral
      acute abscess tonsillectomy in selected patients. An algorithm is proposed for
      the management of peritonsillar abscess based on age, prior history of pharyngo
      tonsillar infections, aspirin intake, and clinical improvement after initial
      drainage and antibiotherapy. EBM RATING: C.

PMID- 16274802
TI  - Comparison of delivery of topical medications to the paranasal sinuses via
      "vertex-to-floor" position and atomizer spray after FESS.
AB  - INTRODUCTION: Topical nasal medications are frequently employed for persistent
      sinonasal symptoms after functional endoscopic sinus surgery (FESS) in chronic
      rhinosinusitis patients. The optimal means for the delivery of these medications
      is unclear. In this study, the efficacy of the vertex to floor (VF) position
      compared to atomizer spray was evaluated in post-FESS patients. METHODS: Three
      trials were performed: two trials in which patients maintained the VF position
      for 1 and 5 minutes, respectively, after nasal drop administration were compared
      to a third trial utilizing an atomizer spray in the upright position. Two
      independent observers rated the distribution of fluorescein-dyed dexamethasone
      drops at 5 sinonasal sites: maxillary sinus (MS), ethmoid cavity (EC), frontal
      recess (FR), sphenoid sinus (SS), and olfactory cleft (OC). RESULTS: VF position
      consistently delivered nasal drops to the MS, EC, SS, and OC. The atomizer
      distributed drops to the MS, EC, SS, and FR. The greatest difference was noted
      with the nasal drops in the olfactory cleft in the VF position; statistical
      significance was achieved with ANOVA testing (P = 0.012). Student's paired t test
      comparing trial 1 to 2, 1 to 3, and 2 to 3 demonstrated greater distribution in
      the OC at 5 minutes compared with 1 minute and spray (P = 0.042 and 0.003).
      CONCLUSIONS: The VF position and atomizer spray were both effective in delivery
      of the dexamethasone drops to the paranasal sinuses. This has significant
      implications for management of patients suffering from recalcitrant chronic
      rhinosinusitis and/or sinonasal polyposis through the delivery of topical
      medications to the paranasal sinuses and olfactory cleft. EBM RATING: C.

PMID- 16274803
TI  - Endoscopic endonasal reduction of blowout fractures of the orbital floor.
AB  - OBJECTIVES: The aim of this study was to document the usefulness of the
      endoscopic endonasal approach as a surgical treatment of isolated blowout
      fractures of the orbital floor. STUDY DESIGN: Retrospective study. SETTING:
      Between 1997 and 2003, using only an endonasal endoscopic surgical approach, we
      operated on 62 patients complaining of diplopia due to isolated blowout fractures
      of the orbital floor. In order to perform the endonasal reduction surgery,
      supplemental septoplasty and/or submucous conchotomy were done. Immediately
      following the reduction and the fixation, eye traction tests were performed to
      confirm the ocular motility improvement. Tampon gauzes or balloon catheters were
      used for the temporal fixation to support the orbital floor. RESULTS:
      Postoperatively, diplopia completely disappeared in 55 of the 62 patients (88.7%)
      that were followed over 6 months. CONCLUSION: The high success rate with regard
      to diplopia indicates that the endoscopic endonasal approach may be an
      alternative to extranasal methods. EBM RATING: B-3.

PMID- 16274804
TI  - Arterial embolization in the management of posterior epistaxis.
AB  - OBJECTIVES: Treatment of severe epistaxis can encompass many modalities. Control
      rates with all treatments are good. Morbidity among treatment groups varies.
      Angiographic embolization is one such method that has a very low complication
      rate. Over the last 10 years, it has become the preferred treatment at our
      institution. STUDY DESIGN: Tertiary medical referral centers: OHSU, Portland
      VAMC. MATERIALS AND METHODS: Retrospective review of 70 patients transferred or
      admitted with posterior epistaxis and treated with selective angiographic
      embolization from 1993 to 2002. RESULTS: Patients had bleeding for a median of
      4.5 days prior to admission. 79% were unilateral. Etiology of bleeding was:
      idiopathic (61%), previous surgery (11%), anticoagulants (9%), trauma (7%), and
      other causes (12%). 30% required blood transfusions prior to admission to OHSU
      (average 4.4 units). No patient required a transfusion postoperatively following
      angiographic embolization or during their hospitalization. The internal maxillary
      artery (IMAX) was embolized in 94% (47% unilateral or bilateral IMAX only, 47%
      unilateral or bilateral IMAX in combination with other vessels, 6% other vessels
      besides the IMAX). Mean length of stay was 2.5 days. 86% had minor or no
      complications after the embolization and were discharged within 24 hours. 13% had
      a major rebleed that required surgical intervention within 6 weeks of the
      embolization. One patient had a serious neurological complication. Using the data
      available on 68 of 70 patients, the cost of hospitalization averaged dollar
      18,000 with direct costs of embolization averaging dollar 11,000. CONCLUSIONS:
      Angiographic embolization is a clinically effective treatment for severe
      epistaxis. EBM RATING: C.

PMID- 16274805
TI  - Lipid-based Nose Ointment for Allergic Rhinitis.
AB  - OBJECTIVE: To assess the efficacy of a lipid-based nose ointment in treating
      allergic rhinitis. STUDY DESIGN AND SETTING: Prospective, open, randomized,
      controlled clinical study in the outpatient departments of 2 tertiary care
      centers. RESULTS: No specific adverse effects were observed. The nose ointment
      under investigation led to a significant improvement in sneezing and nasal
      itching (17 patients). There was no significant change for nasal congestion and
      rhinorrhea in the intention-to-treat sets. However, there was still a significant
      drop of the mean relative total symptom score derived from the individual scores.
      All scores remained unchanged in the untreated control group (16 patients).
      CONCLUSION: Topical application of the nose ointment as a supportive treatment
      leads to a significant improvement of symptoms in allergic rhinitis.
      SIGNIFICANCE: The prevalence of allergic rhinitis is about 10% to 20% in the
      population. Our study results are encouraging and should be assessed in further
      research because changes in the therapeutic guidelines may be suggested. EBM
      RATING: A.

PMID- 16274806
TI  - Prevalence of Meniere's disease in general population of Southern Finland.
AB  - OBJECTIVE: To study the prevalence of Meniere's disease (MD) in the general
      population of Southern Finland. STUDY DESIGN AND SETTING: Prospective study based
      on population register data. A questionnaire was sent to 5000 randomly selected
      persons aged 12 years or more living in the Helsinki University Hospital area. We
      enquired about whether recipients had experienced vertigo associated with a
      moving sensation, hearing loss, or tinnitus. For exclusion purposes, we also
      asked about general illnesses, ear infections, former head and ear traumas, noise
      exposure, medication, and use of tobacco and alcohol. To assess the validity of
      the population-based study, we randomly selected a sample of 100 people among
      those reporting vertigo. They were clinically examined at our vestibular unit.
      The clinical examination was supplemented by audiologic and otoneurologic tests.
      RESULTS: The response rate was 63%. In the final study sample of 3116 people, 216
      reported the triad of vertigo, hearing loss, and tinnitus. By using the most
      recent criteria of the Committee on Hearing and Equilibrium of the American
      Academy of Otolaryngology-Head and Neck Surgery, we were able to identify 16
      definite MD patients from the total sample, yielding a prevalence of 513 of
      100,000 persons. Among the 16 MD subjects, 9 patients had already been diagnosed
      with MD and 1 patient was diagnosed during the clinical examination. A peak
      prevalence of 1709 of 100,000 was seen in the age group 61 to 70 years.
      CONCLUSIONS: Our population-based estimate of MD prevalence is much higher than
      in previous reports. EBM RATING: B-3.

PMID- 16274807
TI  - Management of bilateral benign paroxysmal positional vertigo.
AB  - OBJECTIVE: To describe a series of patients with bilateral benign paroxysmal
      positional vertigo (BiBPPV), with respect to demographics, management, and
      outcome. METHODS: All patients who were identified and treated for BiBPPV in a
      previous 36-month period with a minimal follow-up period of 6 months were
      included. Patients were treated with Epley's maneuver (EM) on the side that was
      more symptomatic and that had a greater velocity and amplitude of tortional
      nystagmus. Patients were re-treated according to symptoms and findings on follow
      up visits. RESULTS: Ten patients were identified with BiBPPV. Most patients
      complained of nonlocalized positional vertigo and unsteadiness. Four were males
      and 6 were females, and the mean age was 54 years. There was a positive history
      of recent head trauma in 4 of the patients. All patients recovered after
      performing a mean of 2.6 EMs during a 3-month period. One patient experienced
      unilateral recurrence and was re-treated successfully. CONCLUSION: BiBPPV has
      typical characteristics and can be managed successfully with EM, performed on the
      more symptomatic side, followed by repeated treatments as needed. EBM RATING: C.

PMID- 16274808
TI  - Long-term clinical trial of tinnitus retraining therapy.
AB  - OBJECTIVE: To demonstrate the efficacy of tinnitus retraining therapy (TRT) for
      tinnitus relief compared to a waiting list group and a partially treated group
      (patients that refused prosthesis adaptation). STUDY DESIGN: Prospective non
      randomised clinical assay (n = 158). Visual analogue scale (VAS) for intensity
      and the Tinnitus Handicap Inventory (THI) were evaluated at 12-month period.
      RESULTS: Eighty two percent of the patients that followed TRT improved their
      tinnitus according to their self-evaluation. THI score was reduced from 48% to
      32% and VAS decreased from 6.6 to 5.3 after one year (p < 0.05). TRT patients
      showed a higher improvement on their tinnitus, THI and VAS scores when compared
      with the waiting list patients and with patients that refused prosthesis
      adaptation when recommended (p < 0.05). CONCLUSIONS: TRT improved tinnitus in 82%
      of the subjects and statistically reduced THI and VAS scores after 12 months. TRT
      has shown to be more effective than a waiting list group and partially treated
      patients. EBM RATING: B-2.

PMID- 16274809
TI  - The feasibility of the retrofacial approach to the pediatric sinus tympani.
AB  - OBJECTIVE: To investigate the feasibility of the retrofacial approach to the
      pediatric sinus tympani (ST). STUDY DESIGN AND SETTING: Five pediatric
      cholesteatoma cases, 10 pediatric and 24 adult normal specimens were studied
      retrospectively using high-resolution CT measurements in our university hospital.
      The normal pediatric and adult specimens also underwent temporal bone
      dissections. CT measurements included the depth (d-ST) and the width (w-ST) of
      ST, the distance (F-PSC) from the facial canal to the posterior semicircular
      canal, and the distance (P-ST) from the depth of ST on a line perpendicular to
      the F-PSC line. RESULTS: There were no significant differences in any
      measurements between pediatric and adult normal specimens and between pediatric
      diseased and normal specimens (P > 0.05). The retrofacial approach performed in
      pediatric specimens was no more complex than in adult specimens. F-PSC>3.0 mm and
      P-ST<2.0 mm provided an accessible approach to the pediatric ST. CONCLUSION: The
      retrofacial approach can be used in selected pediatric cases. SIGNIFICANCE: This
      approach plays its individual role to eradicate cholesteatoma in a difficult-to
      reach pediatric ST. EBM RATING: B-2.

PMID- 16274810
TI  - Cartilaginous choristoma of the bony external auditory canal: a study of 36
      cases.
AB  - OBJECTIVE: The study goal is to present the clinical data of 36 cases of
      heterotopic cartilaginous mass in the bony external auditory canal and to clarify
      the terminology used to describe this clinical entity. STUDY DESIGN AND SETTING:
      We conducted a medical record review of 36 consecutive patients with lesions (26
      of which were excised) seen at two Departments of Otolaryngology in Taiwan.
      RESULTS: Histopathological examination revealed that all 26 excised lesions were
      composed of mature hyaline cartilage, and on this basis, cartilaginous choristoma
      was diagnosed. CONCLUSION: The presence of a heterotopic cartilaginous mass in
      the bony external ear canal is not as rare as it was once thought to be. The
      descriptive term "cartilaginous choristoma" rather than "chondroma" may be more
      appropriate for these lesions. EBM RATING: C.

PMID- 16274811
TI  - Detection of Helicobacter pylori in the middle ear fluid of patients with otitis
      media with effusion.
AB  - OBJECTIVES: In patients with otitis media with effusion (OME), colonization of
      the middle ear effusion (MEE) by Helicobacter pylori (HP) was investigated. STUDY
      DESIGN: A prospective nonrandomized study with nonpaired, nonmatched controls.
      Smear preparations were immunostained with anti-HP antibody and were subjected to
      Gram staining and Giemsa staining. The rapid urease test (CLO) was done. RESULTS:
      Twelve of 15 smears for MEE were positive for HP by immunohistochemistry and 14
      by Giemsa that were Gram-negative. In 3 with positive immunohistochemistry, the
      CLO was positive. CONCLUSION: The results suggest that HP may exist in the MEE of
      some patients with OME.

PMID- 16274812
TI  - Total nasopharyngeal stenosis: treatment with laser excision, nasopharyngeal
      obturators, and topical mitomycin-c.
AB  - OBJECTIVE: Severe nasopharyngeal stenosis after uvulopalatopharyngoplasty (UPPP)
      is a dreaded complication. Very little has been written about successful
      treatment because attempts at correction frequently fail. Severe stenosis of the
      nasopharynx drastically worsens speech, swallowing, and obstructive sleep apnea
      (OSA). We present our successful experience with severe stenosis focusing on a
      simple functional repair using topical mitomycin-c as well as differing daytime
      and nighttime palatal obturators. METHODS: Three adults with total or near-total
      nasopharyngeal stenosis secondary to UPPP were referred to our institution after
      multiple failed attempts at repair. Each presented with significant OSA on
      polysomnogram (PSG), with excessive daytime somnolence and voice and swallowing
      complaints. Under general anesthesia, a CO2 laser is used to create an opening in
      the nasopharynx. Removable and adjustable palatal obturators are fashioned to
      keep the nasopharynx open with a daytime insert piece with a small obturator hole
      for diminished velopharyngeal insufficiency and a nighttime piece without an
      insert to maximize recumbent airflow. Obturators are removed 6 months later with
      topical application of mitomycin-c as a fibroblast inhibitor. All patients were
      followed clinically for at least 1 year and received posttreatment PSG. RESULTS:
      All patients experienced resolution of their stenoses. Swallowing and voice
      complaints resolved. Either OSA was eliminated or any residual OSA was
      successfully treated with nasal continuous positive airway pressure. Serial
      videoendoscopic images throughout the treatment phase demonstrate the
      effectiveness of this new technique. CONCLUSIONS: Severe nasopharyngeal stenosis
      is a rare but devastating complication of UPPP. We introduce a simple technique
      that uses functional palatal obturators and topical mitomycin-c and describe our
      success with this treatment algorithm.

PMID- 16274813
TI  - Obstructing rhinophyma: a case report.

PMID- 16274814
TI  - Peppermint oil chemical burn.

PMID- 16274815
TI  - Superglue (cyanoacrylate) in the nose.

PMID- 16274816
TI  - Malignant solitary fibrous tumor of the hypopharynx with dysphagia.

PMID- 16274817
TI  - Airway-obstructing laryngeal candidiasis in an immunocompetent host.

PMID- 16274818
TI  - Abnormally high bifurcation of the brachiocephalic trunk as a potential operative
      hazard: case report.

PMID- 16274819
TI  - Penetrating rubber bullet into the ethmoid sinus: should the bullet be removed?

PMID- 16274820
TI  - Age-related histopathologic changes in the human cochlea.

PMID- 16274821
TI  - Different canalith repositioning procedures for horizontal canal benign
      paroxysmal positional vertigo.

PMID- 16274822
TI  - Electrocautery tonsillectomy: common practice since the 1930s?

PMID- 16274823
TI  - Editorial comment on "Hyperbaric compression in the guinea pig with perilymph
      fistula".

PMID- 16274824
TI  - A systematic approach to determine global thermal inactivation parameters for
      various food pathogens.
AB  - Thermal inactivation of pathogens has been studied extensively, which has
      resulted in a wide range of D- and z-values. Estimating the inactivation rate for
      a specific condition based on these reported values is difficult, since one has
      to select representative conditions, and data obtained exactly at the required
      representative conditions are generally not available. Therefore, a first step
      could be to globally assess a heat treatment taking into account largest effects
      only. Once the most important parameters are known, a more precise study of
      inactivation can be performed. Therefore, in this study a large quantity of D
      values (n=4066) was collected from literature for various pathogens and linear
      regression was applied to obtain average D-values (together with the 95% upper
      prediction level) and z-values. When comparing these overall data, it can be seen
      that most factors reported to have an effect on the D-value are smaller than the
      variability of all published D-values. Even effects of shoulders disappear in the
      overall analysis. Only a limited number of factors that did have a significant
      effect (p<0.05) on the D-value were identified: for Salmonella spp., the presence
      of chocolate ingredients gave protection to the cells, for Listeria monocytogenes
      the presence of 10% salt (or a(w)<0.92) resulted in a higher heat resistance, for
      Bacillus cereus there were significant differences for various strains and in
      oily products and for Clostridium botulinum there were significant differences in
      heat resistance between different types of C. botulinum. This does not mean that
      other effects do not occur, but it shows the main effects that have to be
      included for a first impression on the performance of a heating process. The
      obtained 95% upper prediction levels of the D-values can be used as a
      (conservative) estimate of inactivation and can be used to give order of
      magnitude values in overall process evaluations.

PMID- 16274825
TI  - Overproduction of Pichia pastoris or Plasmodium falciparum protein disulfide
      isomerase affects expression, folding and O-linked glycosylation of a malaria
      vaccine candidate expressed in P. pastoris.
AB  - Production of recombinant malaria proteins in the methylotrophic yeast Pichia
      pastoris has been difficult due to constraints in transcription, translation
      and/or post-translation controls. Use of codon-optimized genes has resolved many
      of the transcriptional controls; however, efforts to overcome translational and
      post-translational modifications involving disulfide bond formation and
      glycosylation have been mostly restricted to knocking-out putative N-linked
      glycosylation sites. We report now on the effect of overproduction of P. pastoris
      protein disulfide isomerase (PpPDI) and Plasmodium falciparum (PfPDI) on
      production of a disulfide-rich P. falciparum transmission-blocking vaccine
      candidate, Pfs25. Pfs25 is expressed in P. pastoris as two isoforms (A and B);
      the A form has been selected for Phase I human studies. Overproduction of PpPDI
      in the P. pastoris Pfs25 production clone markedly enhanced the expression level
      of Pfs25(A) and (B) by 3-fold, while overproduction of PfPDI increased the
      proportion of Pfs25(A) compared to (B). The resultant Pfs25 products were
      purified and fully characterized biochemically. In addition to differences in
      production levels, the mass spectra of PpPDI-Pfs25(A) compared to Pfs25(A) and
      PfPDI-Pfs25(A) were different due to the pattern and level of O-linked
      glycosylation. The overproduction of PpPDI or PfPDI provides new platforms for
      expression of disulfide-rich malaria proteins.

PMID- 16274826
TI  - Application of "oxygen uptake rate-amino acids" associated mode in controlled-fed
      perfusion culture.
AB  - Controlled-fed perfusion, a new operation mode, which combines the advantages of
      fed-batch and perfusion, has been reported to enhance monoclonal antibody
      productivity. The aim of the present study was to further enrich this mode by an
      "oxygen uptake rate-amino acids (OUR-AA)" strategy in which the feeding of amino
      acids was controlled according to the variation of OUR during perfusion. And the
      effects of this strategy on bioreactor productivity and product quality were
      evaluated. Experimental results indicated that by using this "OUR-AA" approach in
      controlled-fed perfusion mode a high viable cell density of more than 1.9 x
      10(7)cells/ml was achieved and the productivity of mAb reached 325 mg/l/d, which
      was significantly increased by nearly twofold over those of the perfusion and fed
      batch process. The residual concentrations of selected amino acids were
      controlled at a relative steady level by OUR during the culture. The
      immunoreactivity and the purity of the antibody were well preserved as the
      culture process was evolving from flask to the controlled-fed perfusion mode. The
      primary application of "OUR-AA" approach in controlled-fed perfusion mode may
      present a novel control strategy to enhance the culture performance and to
      display the potential of this approach in automatic control field.

PMID- 16274827
TI  - Comparative analysis of genome sequences of three isolates of Orf virus reveals
      unexpected sequence variation.
AB  - Orf virus (ORFV) is the type species of the Parapoxvirus genus. Here, we present
      the genomic sequence of the most well studied ORFV isolate, strain NZ2. The NZ2
      genome is 138 kbp and contains 132 putative genes, 88 of which are present in all
      analyzed chordopoxviruses. Comparison of the NZ2 genome with the genomes of 2
      other fully sequenced isolates of ORFV revealed that all 3 genomes carry each of
      the 132 genes, but there are substantial sequence variations between isolates in
      a significant number of genes, including 9 with inter-isolate amino acid sequence
      identity of only 38-79%. Each genome has an average of 64% G+C but each has a
      distinctive pattern of substantial deviation from the average within particular
      regions of the genome. The same pattern of variation was also seen in the genome
      of another parapoxvirus species and was clearly unlike the uniform patterns of
      G+C content seen in all other genera of chordopoxviruses. The availability of
      genomic sequences of three orf virus isolates allowed us to more accurately
      assess likely coding regions and thereby revise published data for 24 genes and
      to predict two previously unrecognized genes.

PMID- 16274828
TI  - Micromachined devices: the impact of controlled geometry from cell-targeting to
      bioavailability.
AB  - Advances in microelectomechanical systems (MEMS) have allowed the
      microfabrication of polymeric substrates and the development of a novel class of
      controlled delivery devices. These vehicles have specifically tailored three
      dimensional physical and chemical features which, together, provide the capacity
      to target cells, promote unidirectional controlled release, and enhance
      permeation across the intestinal epithelial barrier. Examining the biological
      response at the microdevice biointerface may provide insight into the benefits of
      customized surface chemistry and structure in terms of complex drug delivery
      vehicle design. Therefore, the aim of this work was to determine the interfacial
      effects of selective surface chemistry and architecture of tomato lectin (TL)
      modified poly(methyl methacrylate) (PMMA) drug delivery microdevices on the Caco
      2 cell line, a model of the gastrointestinal tract.

PMID- 16274829
TI  - Enhancement of nasal absorption of large molecular weight compounds by
      combination of mucolytic agent and nonionic surfactant.
AB  - For improving the nasal absorption of poorly absorbable hydrophilic compounds,
      the suitability of a combination of a mucolytic agent, N-acetyl-L-cysteine (NAC),
      and a nonionic surfactant, polyoxyethylene (C25) lauryl ether (laureth-25), was
      examined. Rat studies with fluorescent isothiocyanate-labeled dextran (molecular
      weight ca. 4.4 kDa, FD-4) as a model hydrophilic compound revealed dramatic
      enhancement of nasal absorption when NAC and laureth-25 were simultaneously
      applied. The nasal bioavailability of FD-4 in saline solution was 8.2+/-0.6% but
      increased to 40.0+/-5.5% when 5% NAC and 5% laureth-25 were added. This
      synergistic enhancement could result from the mucolytic activity of NAC in
      reducing mucous viscosity by which the accessibilities of FD-4 and laureth-25 to
      the epithelial membrane were increased. Further rat studies proved that this
      formulation increased nasal absorption of salmon calcitonin. Absolute
      bioavailability from saline solution containing 5% NAC and 1% laureth-25 was
      26.8+/-2.2%, 3.5 times that of the commercial calcitonin nasal spray Miacalcin
      (7.7+/-2.1%). The potential of the new formulation to cause tissue damage in
      terms of hemolytic activity and liberation of phospholipid from the nasal
      membranes was nil or slight. The combination of NAC and laureth-25 appears
      suitable for use in development of nasal products for poorly absorbable drugs,
      especially peptide and protein drugs.

PMID- 16274831
TI  - Effect of physicochemical modification on the biodistribution and tumor
      accumulation of HPMA copolymers.
AB  - Copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) are prototypic and well
      characterized polymeric drug carriers that are being broadly implemented in the
      delivery of anticancer therapeutics. To better predict the in vivo potential of
      the copolymers and to describe the biodistributional consequences of
      functionalization, 13 physicochemically different HPMA copolymers were
      synthesized, varying in molecular weight and in the nature and amount of
      functional groups introduced. Upon radiolabeling, the copolymers were injected
      i.v., and their circulation kinetics, tissue distribution and tumor accumulation
      were monitored in rats bearing subcutaneous Dunning AT1 tumors. It was found that
      increasing the average molecular weight of HPMA copolymers resulted in prolonged
      circulation times and in increased tumor concentrations. Conjugation of carboxyl
      and hydrazide groups, as well as introduction of spacer, drug and peptide
      moieties reduced the long-circulating properties of the copolymers and as a
      result, lower levels were found in tumors and in all organs other than kidney.
      Interestingly, however, in spite of the reduced (absolute) tumor concentrations,
      hardly any reduction in the relative levels localizing to tumors was found. Tumor
      to-organ ratios were comparable to unmodified control for the majority of
      chemically modified copolymers, indicating that functionalization does not
      necessarily affect the tumor targeting ability of the copolymers and suggesting
      that HPMA copolymer-based drug delivery systems may prove to be attractive tools
      for more effectively treating various forms of advanced solid malignancy.

PMID- 16274832
TI  - The link between carotid artery disease and ischemic stroke may be partially
      attributable to autonomic dysfunction and failure of cerebrovascular
      autoregulation triggered by Darwinian maladaptation of the carotid baroreceptors
      and chemoreceptors.
AB  - Carotid artery stenosis is generally thought to induce stroke by either
      compromising cerebral perfusion or inciting embolic phenomena. Carotid
      baroreceptors and chemoreceptors are vital adaptations for cerebrovascular
      autoregulation that can behave mal-adaptively in the setting of modern diseases
      such as atherosclerosis. We hypothesize that acute cerebrovascular events may be
      partially attributable to autonomic dysfunction and cerebrovascular
      autoregulatory failure secondary to carotid sensor maladaptations. Specifically,
      we propose that atherosclerotic disease at the carotid bifurcation can interfere
      with baroreceptor and chemoreceptor function by buffering against accurate
      detection of physical and chemical parameters. Misperceptions of hypoxia and
      hypotension can trigger sympathetic bias and autonomic dysfunction which perturb
      cerebrovascular autoregulation and vasomotor tone, thereby compromising cerebral
      perfusion. The preferential association of strokes with morning arousal, stress,
      acute physical activity, winter months, illness, and older age may relate to this
      phenomenon. Sympathetic bias promotes inflammation and coagulation, a link likely
      forged during prehistoric evolution when trauma represented a more significant
      factor in natural selection. In the setting of carotid sensor dysfunction, the
      resulting inflammation and coagulation can promote acute cardiovascular events.
      The ensuing cerebral ischemia can induce further derangement of cerebrovascular
      autoregulation and upregulate adrenergia, inflammation, and coagulation in a feed
      forward manner. Inflammation and coagulation can also exacerbate carotid sensor
      dysfunction by iteratively worsening atherosclerosis. Angioplasty, stenting, and
      endarterectomy may inadvertently cause acute and chronic carotid sensor
      dysfunction through manipulation, material interposition, and balloon-induced
      baroreceptor injury. Acute strokes during these procedures may result from
      carotid sensor dysfunction rather than embolization. Carotid body and sinus
      electro-modulation and non-balloon atherectomy represent new methods to prevent
      or treat cerebrovascular events. Pharmacologic modulation of autonomic balance,
      such as adrenergic blockade, long presumed contraindicated due to risk of
      cerebral hypoperfusion, may counter-intuitively offer benefit during acute
      strokes. Novel diagnostic paradigms may include functional analysis of carotid
      sensors as well as measurement of the anatomic thickness of calcified and non
      calcified plaque near the carotid body. Carotid sensor dysfunction may be a
      source of systemic sympathetic bias and autonomic dysfunction observed during
      aging and, by association, many of the ailments associated with senescence.
      Modulation of carotid sensors may yield pervasive health benefits beyond those
      found by treating cerebrovascular disease.

PMID- 16274830
TI  - Inner ear drug delivery via a reciprocating perfusion system in the guinea pig.
AB  - Rapid progress in understanding the molecular mechanisms associated with cochlear
      and auditory nerve degenerative processes offers hope for the development of gene
      transfer and molecular approaches to treat these diseases in patients. For
      therapies based on these discoveries to become clinically useful, it will be
      necessary to develop safe and reliable mechanisms for the delivery of drugs into
      the inner ear, bypassing the blood-labyrinthine barrier. Toward the goal of
      developing an inner ear perfusion device for human use, a reciprocating
      microfluidic system that allows perfusion of drugs into the cochlear perilymph
      through a single inlet hole in scala tympani of the basal turn was developed. The
      performance of a prototype, extracorporeal reciprocating perfusion system in
      guinea pigs is described. Analysis of the cochlear distribution of compounds
      after perfusion took advantage of the place-dependent generation of responses to
      tones along the length of the cochlea. Perfusion with a control artificial
      perilymph solution had no effect. Two drugs with well-characterized effects on
      cochlear physiology, salicylate (5 mM) and DNQX (6,7-Dinitroquinoxaline-2,3
      dione; 100 and 300 microM), reversibly altered responses. The magnitude of drug
      effect decreased with distance from the perfusion pipette for up to 10 mm, and
      increased with dose and length of application.

PMID- 16274833
TI  - Canalicular membrane localization of hepatocyte aquaporin-8 is preserved in
      estradiol-17beta-D-glucuronide-induced cholestasis.

PMID- 16274834
TI  - A phase I trial of an antisense inhibitor of hepatitis C virus (ISIS 14803),
      administered to chronic hepatitis C patients.
AB  - BACKGROUND/AIMS: ISIS 14803 is a 20-unit antisense phosphorothioate
      oligodeoxynucleotide that binds to hepatitis C virus (HCV) RNA at the translation
      initiation region of the internal ribosome entry site (IRES) and inhibits protein
      expression in cell culture and mouse models. This Phase I, open-label, dose
      escalation trial of ISIS 14803 was performed in chronic HCV patients. METHODS: At
      least 7 days after receiving an initial single dose, twenty-eight patients
      received 0.5-3 mg/kg ISIS 14803 thrice weekly for 4 weeks by intravenous infusion
      or subcutaneous injection. RESULTS: In most patients, the 4-week treatment did
      not reduce plasma HCV RNA. However, 3 patients receiving > or =2 mg/kg had
      transient HCV reductions of 1.2-1.7 log(10) that persisted < or =32 days. These
      reductions were accompanied by asymptomatic, self-resolving elevations in serum
      alanine transaminase (ALT) levels to >10x the upper limit of normal. Two other
      patients had ALT flares without plasma HCV reduction. No clinical signs, symptoms
      of hepatic dysfunction, or laboratory changes in albumin or prothrombin time
      accompanied ALT elevations. CONCLUSIONS: ISIS 14803 treatment was associated with
      HCV reductions in only 3/28 patients. ALT flares in 5 patients also occurred.
      Further studies to evaluate ISIS 14803 treatment and the mechanisms of the ALT
      flares are now required.

PMID- 16274835
TI  - Safety and efficacy of adefovir dipivoxil in patients infected with lamivudine
      resistant hepatitis B and HIV-1.
AB  - BACKGROUND/AIMS: Adefovir dipivoxil (10 mg once-daily) was added to
      antiretroviral therapy including lamivudine in 35 HIV/HBV co-infected patients.
      METHODS: Parameters evaluated included alanine aminotransferase (ALT), HBV DNA
      and serological markers, HIV-1 RNA, and CD4+ cell count. RESULTS: Twenty-nine
      patients (83%) completed 144 weeks. Serum HBV DNA declined from a baseline 9.76
      log10 copies/mL (median) to 4.68, 5.24, and 5.90 log10 copies/mL at weeks 48, 96,
      and 144, respectively (P<0.0001 at all time points). Seven patients (25%)
      achieved HBV DNA<2.3 log10 copies/mL. No adefovir-associated resistance mutations
      in HBV DNA polymerase or HIV-1 reverse transcriptase were detected. ALT declined
      from 81 IU/L (median) at baseline by -16.0, -44.5, and -46.0 IU/L at week 48, 96
      and 144, respectively (P=<0.05, respectively), and normalized in 71% of patients
      (20 of 28) by week 144. Two patients developed antibodies against HB 'e' antigen
      by week 48. No serious adverse events related to adefovir dipivoxil occurred
      during the study, and HIV-1 RNA and CD4+ cell counts were stable. CONCLUSIONS:
      Treatment with adefovir dipivoxil for 144 weeks was well tolerated and resulted
      in significant and sustained reductions in HBV DNA and ALT in HIV/HBV co-infected
      patients. Efficacy increased with treatment duration, with no loss of viral
      suppression.

PMID- 16274836
TI  - Histological-hemodynamic correlation in cirrhosis-a histological classification
      of the severity of cirrhosis.
AB  - BACKGROUND/AIMS: While the definitive diagnosis of cirrhosis is histological, it
      is the degree of portal hypertension, as determined by the hepatic venous
      pressure gradient (HVPG), that is an important determinant of the severity of
      cirrhosis. An HVPG > or =10 mmHg (termed clinically significant portal
      hypertension or CSPH) is predictive of the development of complications of
      cirrhosis, including death. This study aimed to determine the relationship
      between specific histological parameters and HVPG in cirrhosis. METHODS: Forty
      three patients with biopsy-proven cirrhosis and HVPG measurements within 6 months
      of the biopsy were included in the study. The following parameters were scored
      semiquantitatively and without knowledge of HVPG results: sinusoidal fibrosis,
      septal thickness, loss of portal tracts and central veins, nodule size,
      inflammation, steatosis, and iron. RESULTS: Septal thickness (p=0.03), small
      nodularity (p=0.003), loss of portal tracts (p=0.01), inflammation (p=0.04) and
      alcoholic etiology (p=0.01) correlated with the presence of CSPH. However, small
      nodularity and septal thickness were the only parameters independently predictive
      of CSPH (r=0.658, p<0.05). CONCLUSIONS: We describe a subclassification of
      histological cirrhosis based on the severity of portal hypertension that consists
      of a combination of nodule size and septal thickness, with small nodularity and
      thick septa being independent predictors of the presence of CSPH.

PMID- 16274837
TI  - Non-alcoholic steatohepatitis: from cell biology to clinical practice.

PMID- 16274838
TI  - A modified OSEM algorithm for PET reconstruction using wavelet processing.
AB  - Ordered subset expectation-maximization (OSEM) method in positron emission
      tomography (PET) has been very popular recently. It is an iterative algorithm and
      provides images with superior noise characteristics compared to conventional
      filtered backprojection (FBP) algorithms. Due to the lack of smoothness in images
      in OSEM iterations, however, some type of inter-smoothing is required. For this
      purpose, the smoothing based on the convolution with the Gaussian kernel has been
      used in clinical PET practices. In this paper, we incorporated a robust wavelet
      de-noising method into OSEM iterations as an inter-smoothing tool. The proposed
      wavelet method is based on a hybrid use of the standard wavelet shrinkage and the
      robust wavelet shrinkage to have edge preserving and robust de-noising
      simultaneously. The performances of the proposed method were compared with those
      of the smoothing methods based on the convolution with Gaussian kernel using
      software phantoms, physical phantoms, and human PET studies. The results
      demonstrated that the proposed wavelet method provided better spatial resolution
      characteristic than the smoothing methods based on the Gaussian convolution,
      while having comparable performance in noise removal.

PMID- 16274839
TI  - Tolloid-like 1 is negatively regulated by stress and glucocorticoids.
AB  - Glucocorticoids affect a variety of tissues to enable the organism to adapt to
      the stress. Hippocampal neurons contain glucocorticoid receptors and respond to
      elevated glucocorticoid levels by down-regulating the HPA axis. Chronically,
      however, stress is deleterious to hippocampal neurons. Chronically elevated
      levels of glucocorticoids result in a decrease in the number of dendritic spines,
      reduced axonal growth and synaptogenesis, and decreased neurogenesis in the
      hippocampus. Tolloid-like 1 (Tll-1) is a metalloprotease that potentiates the
      activity of the bone morphogenetic proteins (BMPs). Neurogenesis in the
      hippocampus of both developing and adult mammals requires BMPs. In this study, we
      demonstrate that Tll-1 expression is increased in mice that have increased
      neurogenesis. The Tll-1 promoter contains glucocorticoid response elements which
      are capable of binding to purified glucocorticoid receptor. Glucocorticoids
      decrease Tll-1 expression in vitro. Finally, prenatal stress leads to a decrease
      in Tll-1 mRNA expression in the hippocampus of adult female mice that is not
      observed in adult male mice indicating that Tll-1 expression is differentially
      regulated in males and females. The results of this study indicate that Tll-1 is
      responsive to glucocorticoids and this mechanism might influence neurogenesis in
      the hippocampus.

PMID- 16274840
TI  - Partial cloning of neuronal nitric oxide synthase (nNOS) cDNA and regional
      distribution of nNOS mRNA in the central nervous system of the Nile tilapia
      Oreochromis niloticus.
AB  - A constitutive NOS complementary DNA (cDNA) was partially cloned by RT-PCR from
      the brain of a teleost, the Nile tilapia (Oreochromis niloticus), using
      degenerate primers against conserved regions of NOS. The predicted 206-long amino
      acid sequence showed a high degree of identity with other vertebrate neuronal NOS
      (nNOS) protein sequences. In addition, phylogenetic analysis revealed that Nile
      tilapia NOS clustered with other known nNOS. Using the coupled reaction of semi
      quantitative RT-PCR and Southern blotting, the basal tissue expression pattern of
      the cloned nNOS gene was investigated in discrete areas of the central nervous
      system (CNS) and in the heart and skeletal muscle tissue. As revealed, expression
      of nNOS transcripts was detected in all the CNS regions examined, whereas nNOS
      gene was not expressed in the heart and skeletal muscle. The distribution pattern
      of nNOS gene expression showed the highest expression levels in the forebrain
      followed by the optic tectum, the brainstem and the spinal cord, whereas scarce
      expression was detected in the cerebellum. Cellular expression of nNOS mRNA was
      analyzed in the CNS by means of in situ hybridization. According to the RT-PCR
      results, most nNOS mRNA expressing neurons are localized in the telencephalon and
      diencephalon, whereas in the mesencephalic optic tectum, the brainstem and the
      spinal cord, nNOS mRNA expressing neurons are relatively more scattered. A very
      low hybridization signal was detected in the cerebellar cortex. These results
      suggest that NO is involved in numerous brain functions in teleosts.

PMID- 16274841
TI  - Molecular regulation of glutamate and GABA transporter proteins by clobazam
      during epileptogenesis in Fe(+++)-induced epileptic rats.
AB  - To assess the molecular effects of the antiepileptic drug clobazam (CLB, 1,5
      benzodiazepine), a benzodiazepine effective in the management of epilepsy, we
      performed a series of experiments using rats with chronic, spontaneous recurrent
      seizures induced by amygdalar injection of FeCl(3). Experimental animals were
      treated for 14 days with CLB. We then measured the expression of glutamate and
      GABA transporter proteins and evaluated the changes that occurred in these
      proteins using both experimental and control animals. CLB treatment was
      associated with an increase in the production of GLT-1 in the contra-lateral
      hippocampus of animals receiving amygdalar FeCl(3) and CLB treatment. CLB
      treatment up-regulated the GABA transporter GAT3 in the contra-lateral
      hippocampus of animals with chronic, recurrent seizures. In contrast, CLB had no
      effect on the expression of EAAC1 and GAT1 in the hippocampus or the cortex in
      control animal groups. Chronic epileptogenesis may be associated with down
      regulation of the production of glial excitatory amino acid transporters, GLAST
      and GLT-1, proteins that cause increase in the basal extracellular concentrations
      of glutamate. Elevated GABA transporter expression results in increased reverse
      transport of GABA to the extracellular space during periods of excitation. In
      addition to allosteric activation of GABA(A) receptors, this study suggests that
      CLB might exhibit its antiepileptic action by increasing GLT-1 expression and
      GAT3 in the hippocampus of rats with chronic seizures.

PMID- 16274842
TI  - Effect of nonionic surfactant partitioning on the dissolution kinetics of
      residual perchloroethylene in a model porous medium.
AB  - At concentrations above the critical micelle concentration, surfactants can
      significantly enhance the solubilization of residual nonaqueous phase liquids
      (NAPL) and, for this reason, are the focus of research on surfactant-enhanced
      aquifer remediation (SEAR). As a consequence of their amphiphilic nature,
      surfactants may also partition to various extents between the organic and aqueous
      phases, thereby affecting SEAR performance. We report here on the observation and
      analysis of the effect of surfactant partitioning on the dissolution kinetics of
      residual perchloroethylene (PCE) by aqueous solutions (1000 mg/L) of the non
      ionic surfactant Triton X-100 in a model porous medium. For this fluid system,
      batch equilibration experiments showed that the surfactant partitions strongly
      into the NAPL (NAPL-water partition coefficient equal to 12.5). Dynamic
      interfacial tension (IFT) measurements were employed to study surfactant
      diffusion and interfacial adsorption. The dynamic IFT measurements were
      consistent with partitioning of the surfactant between the two liquid phases. PCE
      dissolution experiments, conducted in a transparent glass micromodel using an
      aqueous surfactant solution, were contrasted to experiments using clean water.
      Surfactant partitioning was observed to delay significantly the onset of micellar
      solubilization of PCE, an observation reproduced by a numerical model. This
      effect is attributed to the reduction of surfactant concentration in the
      immediate vicinity of the NAPL-water interface, which accompanies transport of
      the surfactant into the NAPL. Accordingly, it is suggested that both the rate and
      the extent of diffusion of the surfactant into the NAPL affect the onset of and
      the driving force for micellar solubilization. While many surfactants do not
      readily partition in NAPL, this possibility must be considered when selecting non
      ionic surfactants for the enhanced solubilization of residual chlorinated
      solvents in porous media.

PMID- 16274843
TI  - Inhibition of prohormone convertase 1 (PC1) expression in cholecystokinin (CCK)
      expressing At-T20 cells decreased cellular content and secretion of CCK and
      caused a shift in molecular forms of CCK secreted.
AB  - Two different RNAi methods were used to inhibit the expression of prohormone
      convertase 1 (PC1) in At-T20 cells. Transient transfection of double stranded RNA
      and stable expression of a vector expressing hairpin-loop RNA targeting PC1
      reduced cholecystokinin (CCK) secretion from At-T20 cells. PC1 mRNA and protein
      were also decreased in the vector transfected cells. This treatment caused a
      shift in the forms of cholecystokinin (CCK) secreted, decreasing CCK 22 and
      increasing CCK 8. Stable expression of RNAi effectively decreased PC1 expression.
      The observed decrease in CCK seen with these RNAi treatments further supports a
      role for PC1 in CCK processing in these cells.

PMID- 16274844
TI  - alpha-Melanocyte stimulating hormone, inflammation and human melanoma.
AB  - Alpha-melanocyte stimulating hormone (alpha-MSH) arises from the proteolytic
      cleavage of proopiomelanocortin (POMC) and is the most potent naturally occurring
      melanotropic peptide. The biological effects of alpha-MSH are mediated via
      melanocortin receptors (MCRs), which are expressed in virtually every cutaneous
      cell type. alpha-MSH has pleiotrophic functions including the modulation of a
      wide range of inflammatory stimuli such as proinflammatory cytokines, adhesion
      molecules and inflammatory transcription factors. All of the former would be
      consistent with a cytoprotective role for this hormone in protecting skin cells
      from exogenous stress, as would occur following UV exposure or exposure to agents
      inducing inflammation or oxidative stress. In addition to actions on normal skin
      cells it also modulates both cutaneous and uveal melanoma cell behavior. With
      respect to melanoma, alpha-MSH is intriguing as studies have shown that while
      alpha-MSH has the potential to retard metastatic spread (by reducing cell
      migration and invasion) it is also capable of reducing the ability of the immune
      system to detect tumor cells (by down regulating adhesion molecules that would
      normally assist in immune cell interaction with melanoma cells). This review
      considers the evolving biology of alpha-MSH and discusses its role in man that
      extend far beyond pigmentation of skin melanocytes, suggesting that the
      detoxifying role of alpha-MSH in inducing melanogenesis is only one aspect of the
      stress-coping role of this hormone. Indeed melanoma cells may owe at least some
      of their success to the 'protective' role of alpha-MSH.

PMID- 16274845
TI  - Immobilized alpha-melanocyte stimulating hormone 10-13 (GKPV) inhibits tumor
      necrosis factor-alpha stimulated NF-kappaB activity.
AB  - alpha-MSH is an anti-inflammatory peptide which signals by binding to the
      melanocortin-1 receptor (MC1R) and elevating cyclic AMP in several different
      cells and tissues. The carboxyl terminal peptides of alpha-MSH (KPV/GKPV) are the
      smallest minimal sequences that prevent inflammation, but it is not known if they
      operate via MC1R or cyclic AMP. The aim of this study was to examine the
      intracellular signaling potential of the GKPV peptide sequence when immobilized
      to polystyrene beads via a polyethylene glycol moiety. Beads containing an
      immobilized GKPV peptide were investigated for their ability to inhibit
      proinflammatory tumor necrosis factor-alpha (TNF-alpha) stimulated activation of
      NF-kappaB in HBL cells stably transfected with an NF-kappaB-luciferase reporter
      construct. Peptide functionalized beads were compared with the ability of soluble
      peptide alone (alpha-MSH or GKPV) or non-functionalized beads to inhibit TNF
      alpha stimulated activation of NF-kappaB. GKPV peptide functionalized beads
      significantly inhibited NF-kappaB-luciferase activity in comparison to beads
      containing no peptide moiety in one of two growths conditions investigated.
      Soluble alpha-MSH and GKPV peptides were also confirmed to inhibit NF-kappaB
      luciferase. The present study suggests that the carboxyl terminal MSH peptide
      acts via a cell receptor-based mechanism and furthermore may support the
      potential use of such immobilized ligands for anti-inflammatory therapeutic use.

PMID- 16274846
TI  - Circumventing central leptin resistance: lessons from central leptin and POMC
      gene delivery.
AB  - We identified that leptin resistance in aged-obese rats has both peripheral and
      central components. The central resistance is characterized by diminished
      hypothalamic leptin receptors and impaired leptin signal transduction. We
      developed a new model of leptin-induced leptin resistance in which application of
      the central leptin gene delivery produces unabated hypothalamic leptin over
      expression. The chronic central elevation of leptin precipitates leptin
      resistance in young animals devoid of obesity and exacerbates it in mature or
      aged animals with obesity. Despite leptin resistance, our aged obese, DIO, and
      leptin-induced leptin resistant rats were fully responsive to central
      pharmacological melanocortin activation. We propose that the central leptin
      resistance resides between leptin receptor and melanocortin receptor activation.
      Our central POMC gene therapy overcame leptin resistance, producing weight and
      fat loss and improved insulin sensitivity in obese Zucker and aged rats. This
      success highlights the central melanocortin system as a useful drug target for
      combating obesity.

PMID- 16274847
TI  - Development of novel LL-37 derived antimicrobial peptides with LPS and LTA
      neutralizing and antimicrobial activities for therapeutic application.
AB  - New peptides for lipopolysaccharide (LPS) and lipoteichoic acid (LTA)
      neutralization in upper respiratory tract infections were developed and evaluated
      in terms of efficacy and safety for application in humans. Based on the sequence
      of the human antimicrobial peptide LL-37 we developed and investigated length
      variants, substitution analogues and modifications to stabilize the peptides to
      prevent enzymatic degradation and to improve efficacy. The most promising peptide
      appears P60.4, a 24 amino acid peptide with similar efficacy as LL-37 in terms of
      LPS and LTA neutralization and lower pro-inflammatory activity. In addition, the
      acetylated and amidated version of this peptide shows no toxicity and displays
      higher or equal antimicrobial activity compared to LL-37.

PMID- 16274848
TI  - Role of hypothalamic interleukin-1beta (IL-1beta) in regulation of energy
      homeostasis by melanocortins.
AB  - In the current study we sought to determine whether hypothalamic IL-1beta is
      regulated by melanocortin signaling and if melanocortin-induced changes in energy
      balance are dependent on IL-1beta. A melanocortin agonist, MTII, increased
      hypothalamic IL-1beta mRNA levels by two-fold, whereas a melanocortin antagonist,
      SHU9119, blunted lipopolysaccharide (LPS)-mediated increase of hypothalamic IL
      1beta content. Pharmacological or genetic disruption of IL-1 receptor signaling
      prevented MTII-mediated reductions in locomotor activity, but did not reduce MTII
      induced anorexia. These data suggest a potential role for central melanocortins
      in mediating the decrease of ambulation characteristic of the 'sickness'
      response.

PMID- 16274849
TI  - Cardiovascular responses to melanocortin 4-receptor stimulation in conscious
      unrestrained normotensive rats.
AB  - In the present studies, we used a non-selective melanocortin MC3/4 receptor
      agonist (HP228) and a novel selective melanocortin MC4 receptor (MC4-R) agonist
      (MK-cpd1) to study the cardiovascular, temperature, locomotor and feeding
      responses to melanocortin receptor stimulation in comparison to sibutramine in
      rats instrumented with a telemetry transmitter. Moreover, norepinephrine turnover
      rates in heart and brown adipose tissue were determined. HP228 (1, 3 and 10mg/kg,
      i.p.) reduced 24h food intake dose-dependently and increased heart rate and mean
      arterial pressure (maximal differences: +60+/-8beats/min and +8+/-1mmHg, means+/
      S.E.M., p<0.001 and p<0.01, respectively). After 10mg/kg HP228 showed a three
      fold increase in norepinephrine turnover in the heart. The selective MC4-R
      agonist MK-cpd1 tended to decrease 24h food intake only at the highest dose
      tested (10mg/kg, i.p., p=0.06) and increased both heart rate (+17+/-4 and +22+/
      5beats/min at 3 and 10mg/kg, p<0.01) and mean arterial pressure (+4+/-1mmHg at
      10mg/kg, p<0.05). Sibutramine reduced food intake at all doses tested (1, 3 and
      10mg/kg, i.p.). It did not change mean arterial pressure significantly, and
      increased heart rate only at the highest dose tested (+36+/-6beats/min, p<0.05).
      If also observed in humans, the pharmacological profile of MC4-R agonists would
      not offer a significant therapeutic advantage over currently used appetite
      suppressants such as sibutramine.

PMID- 16274850
TI  - Trends in the evolution of the prodynorphin gene in teleosts: cloning of eel and
      tilapia prodynorphin cDNAs.
AB  - The detection of the prodynorphin gene in anuran amphibians and lungfishes may
      indicate that this gene arose as a result of the duplication of the proenkephalin
      gene early during the divergence of the Sarcopterygii, or that this gene may
      predate the divergence of the ray-finned fish and the lobe-finned fish. The
      cloning of prodynorphin-related genes from the pufferfish and zebrafish supports
      the latter hypothesis. This study analyzes trends in the radiation of the
      prodynorphin gene in teleosts. Prodynorphin cDNAs were cloned from the brain of
      the eel Anguilla rostrata and the Nile tilapia, Oreochromis niloticus. These
      teleost prodynorphin sequences have distinct alpha-neoendorphin, dynorphin A, and
      dynorphin B sequences, and a novel opioid sequence, YGGFI. The relationship of
      these teleost prodynorphin sequences to other actinopterygian and sarcopterygian
      prodynorphin sequences will be discussed.

PMID- 16274851
TI  - Obesity-associated mutations in the human melanocortin-4 receptor gene.
AB  - Mutations in the human melanocortin-4 receptor (MC4R) gene have been associated
      with severe obesity. Many of the mutations result in partial or complete loss-of
      function based on the nature of the mutation or the function of mutated receptors
      when tested in heterologous expression systems. This review discusses the role of
      MC4R in the central regulation of body weight, the pathogenic mechanisms of the
      mutations, and the validity of MC4R as an anti-obesity drug target.

PMID- 16274852
TI  - The melanocortin system during fasting.
AB  - This paper sets out to review the implication of the melanocortin system in
      regulating feeding behavior and energy balance during short- and long-term food
      deprivation. It is discussed in relation to: (1) body fat exhaustion and the
      known enhanced drive for refeeding in late fasting and (2) peripheral hormonal
      status with emphasis on the effect of leptin administration on melanocortin gene
      expression according to fat store mobilization.

PMID- 16274853
TI  - The regulation of food intake by selective stimulation of the type 3 melanocortin
      receptor (MC3R).
AB  - High levels of binding sites for melanocortin peptides exist within the arcuate
      nucleus, and a functional response to melanocortin peptides has been demonstrated
      in arcuate POMC neurons. Because the MC3R is thought to function as an inhibitory
      autoreceptor on POMC neurons, we reasoned that peripheral injections of MC3R
      specific agonists would act within the arcuate nucleus to inhibit POMC neurons
      and thereby stimulate feeding. We demonstrate that the peptidergic MC3R agonist,
      d-Trp(8)-gamma-MSH, stimulates feeding via the MC3R when injected peripherally.
      These data provide the first evidence that feeding can be stimulated by
      peripheral injection of MC3R-specific agonists.

PMID- 16274854
TI  - The role of polyamines in glucagon-like peptide-2 prevention of TPN-induced gut
      hypoplasia.
AB  - Total parenteral nutrition (TPN) of rats has been demonstrated to produce
      hypoplasia of gut mucosa, and to be associated with reduced immune response and
      elevated translocation of bacteria from gut to mesenteric lymph nodes, spleen and
      liver. Treatment of rats being maintained on TPN with the proglucagon fragment,
      glucagon-like peptide-2 (GLP-2), has been shown to totally prevent small
      intestine mucosal hypoplasia. In the present study, we found that depletion of
      polyamines with alpha-difluromethylornithine (DFMO) significantly reduced the
      efficacy of GLP-2 in preserving gut mucosa in rats maintained on TPN for 8 days.
      Co-infusion of GLP-2 with TPN prevented loss of protein and mucosa in duodenum,
      jejunum and ileum, but not in colon. Addition of DFMO to the infusate prevented
      the protective effects of GLP-2 in the duodenum and jejunum. In the jejunum,
      putrescine and spermidine were reduced in DFMO-treated rats, while the ileum
      exhibited reductions of these polyamines in rats infused with TPN or TPN plus GLP
      2. DFMO infusion further reduced these polyamines in the ileum, while levels of
      spermine were increased. Concentrations of ornithine decarboxylase were elevated
      in jejunum of rats infused with TPN or TPN plus GLP-2, but were reduced
      significantly in DFMO-treated rats. These results suggest that normal levels of
      polyamines are necessary for the expression of GLP-2-induced hyperplasia.
      Differential effects of GLP-2 and DFMO across gut segments may relate to regional
      differences in proliferative and anti-apoptotic effects of the treatments.

PMID- 16274855
TI  - Melanocyte stimulating hormone peptides inhibit TNF-alpha signaling in human
      dermal fibroblast cells.
AB  - Alpha-melanocyte stimulating hormone (alpha-MSH) has been identified as a potent
      anti-inflammatory in various tissues including the skin. It has previously been
      shown in skin cell keratinocytes and melanocytes/melanoma cells that MSH peptides
      inhibit TNF-alpha stimulated NF-kappaB activity and intercellular adhesion
      molecule-1 (ICAM-1) upregulation. However, the precise anti-inflammatory role of
      MSH peptides in dermal fibroblasts is unclear. Some studies report on pro
      inflammatory responses, while others on anti-inflammatory responses. The present
      study confirms MC1R expression in cultured human dermal fibroblasts and reports
      that the MSH peptides alpha-MSH and KP(-D-)V inhibit TNF-alpha stimulated NF
      kappaB activity and ICAM-1 upregulation, consistent with an anti-inflammatory
      role. However, involvement of IkappaB-alpha regulation by either peptide was not
      confirmed, supporting a mechanism independent of the NF-kappaB inhibitor. In
      conclusion, alpha-MSH and KP(-D-)V peptides have an anti-inflammatory action on
      dermal fibroblast signaling by inhibiting the pro-inflammatory activity of TNF
      alpha in vitro.

PMID- 16274856
TI  - Blockade of the insulin-like growth factor I receptor in the choroid plexus
      originates Alzheimer's-like neuropathology in rodents: new cues into the human
      disease?
AB  - The possibility that perturbed insulin/insulin-like growth factor I (IGF-I)
      signalling is involved in development of late-onset forms of Alzheimer's disease
      (AD) is gaining increasing attention. We recently reported that circulating IGF-I
      participates in brain amyloid beta (Abeta) clearance by modulating choroid plexus
      function. We now present evidence that blockade of the IGF-I receptor in the
      choroid plexus originates changes in brain that are reminiscent of those found in
      AD. In rodents, IGF-I receptor impairment led to brain amyloidosis, cognitive
      disturbance, and hyperphosphorylated tau deposits together with other changes
      found in Alzheimer's disease such as gliosis and synaptic protein loss. While
      these disturbances were mostly corrected by restoring receptor function, blockade
      of the IGF-I receptor exacerbated AD-like pathology in old mutant mice already
      affected of brain amyloidosis and cognitive derangement. These findings may
      provide new cues into the causes of late-onset Alzheimer's disease in humans
      giving credence to the notion that an abnormal age-associated decline in IGF-I
      input to the choroid plexus may contribute to development of AD in genetically
      prone subjects.

PMID- 16274857
TI  - Salivary cortisol and memory function in human aging.
AB  - OBJECTIVE: To examine the association of salivary cortisol with cognitive changes
      in a 3 year longitudinal study. Previous studies have suggested that elevated
      glucocorticoid concentrations alter hippocampal neuronal morphology, inhibit
      neurogenesis, and impair cognition. METHODS: Salivary cortisol samples were
      collected at home by 79 cognitively intact older persons (mean age 78+/-7 years)
      at 08:00, 15:00 and 23:00h, and collections were repeated annually for 3 years.
      Cognitive function was also assessed annually. RESULTS: The mean cortisol level
      of samples taken at three times of day and the cortisol concentration at 23:00h
      were significantly associated with poorer performance on tasks of declarative
      memory and executive function. Of 46 subjects who completed the entire 3 year
      study, higher initial cortisol concentration at 23:00h predicted a decline in
      performance of delayed paragraph recall. CONCLUSION: These results partially
      confirm previous findings that high cortisol is associated with impaired
      declarative memory function in non-demented older persons. In addition, our data
      show that high salivary cortisol concentrations predict a decline in memory
      function over the next 3 years.

PMID- 16274859
TI  - Pisiform ligament complex syndrome and pisotriquetral arthrosis.
AB  - PLC syndrome is a spectrum that encompasses PLC instability and ends with PTA.
      Early recognition and treatment of PLC instability may disrupt its progression to
      PTA. The pisiform tracking test is a provocative maneuver that aids in diagnosing
      PLC syndrome. Pisiformectomy with preservation of the soft tissue confluence
      remains the treatment of choice for severe PLC syndrome that does not respond to
      nonoperative treatment.

PMID- 16274860
TI  - Arthroscopic techniques for wrist arthritis (radial styloidectomy and proximal
      pole hamate excisions).
AB  - Over the last 2 decades, arthroscopy has assumed a greater role in the treatment
      of disorders of the wrist. The arthroscopic treatment of radioscaphoid arthritis
      and ulnar hamate impaction provides the benefits of being minimally invasive,
      with less morbidity, earlier motion, less recovery time, early return to work,
      and greater patient acceptance. Both procedures are performed easily using
      standard arthroscopic techniques without any significant learning curve.Long-term
      studies need to be performed to determine the exact clinical sequelae of excision
      of the proximal pole of the hamate, specifically on the biomechanics of the
      triquetrohamate articulation.

PMID- 16274861
TI  - Arthroscopic synovectomy in wrist arthritis.
AB  - Arthroscopic synovectomy is a safe outpatient procedure with minimal
      postoperative morbidity. In patients who have rheumatoid arthritis and possibly
      also in patients who have JRA, SLE, and postinfectious arthritis, a long period
      of increased comfort and improved function can be anticipated. The procedure may
      be considered in post-traumatic cases with joint contracture and as an adjunct to
      other measures for certain osteoarthritic disorders. In patients who have septic
      arthritis with insufficient clinical improvement after systemic antibiotics and
      lavage, arthroscopic synovectomy seems advantageous.

PMID- 16274862
TI  - Scaphoid excision with four-corner fusion.
AB  - The scaphoid plays a critical role in maintain-ing normal carpal kinematics. SLAC
      and SNAC wrist arthritis demonstrate the ramifications ofscaphoid pathology on
      wrist biomechanics. In the past, symptomatic SLAC or SNAC pathology spelled total
      wrist arthrodesis. Over the past 20 years there has been a movement toward
      limited wrist arthrodesis in the treatment of SLAC/SNAC wrists. In the long-term
      follow-up of four-corner fusions, patient satisfaction is high, patients are able
      to return to their previous vocation, and wrist function averages 60%-70% of the
      contralateral wrist. The Spider plate is a recent advancement in the four-corner
      fusion armamentarium that has thus far shown great promise in respect to fusion
      rates (100% in the first documented series [36]),functional range of motion,
      intercarpal stability[37], and patient satisfaction.

PMID- 16274863
TI  - Scaphotrapeziotrapezoid arthrodesis for arthritis.
AB  - The main indications for scaphotrapeziotrapezoid (STT) fusion are STT arthritis,
      rotary subluxation of the scaphoid, and Kienbock disease. The results of this
      procedure in the literature for each indication are discussed, as are the
      advantages, disadvantages,and alternative procedures. This article discusses the
      authors' surgical technique and results. The authors believe this procedure is a
      viable one in specific clinical scenarios.

PMID- 16274864
TI  - Partial arthrodesis for the rheumatoid wrist.
AB  - The correct treatment of wrist deformation in the patient who has rheumatoid
      arthritis has a major impact on the preservation of function of the hand.
      Surgical decisions should be individualized, based on the patient's needs and the
      future development of deformation. Partial wrist arthrodesis in rheumatoid wrists
      is an excellent tool to preserve stability and functional mobility in the long
      term. In cases of severe destruction complete wrist fusion should be considered
      alternatively.

PMID- 16274865
TI  - Proximal row carpectomy.
AB  - Proximal row carpectomy is extremely useful as a wrist reconstructive technique
      for cases of degenerative joint arthritis of the radiocarpal joint cause by
      scapholunate advanced collapse, scapholunate advanced collapse, schaphoid
      nonunion advanced collapse, trans-scaphoid perilunate fracture dislocations,
      lunate dislocations, and Kienbock disease. It should be selected with caution for
      patients younger than 35 years old. The procedure can be performed with or
      without temporary internal fixation with with Kirschner wires, and adjunctive
      techniques of dorsal capsule interposition, proximal capitate excision, and
      radial styloidectomy can be used. The longevity of the operation is good, but the
      patient should be informed preoperatively that secondary procedures may be
      required. Based on historical series, these procedures have included addition
      have included of radial styloidectomy when this has not been performed at the
      index procedure, revision of the surgery with capitate debridement or conversion
      to total wrist arthodesis. Conversion of proximal row carpectomy to total wrist
      arthoplasty with implants can be contemplated in selected patient particularly as
      newer implants are designed. The technique the senior author has used on occasion
      has been to perform revision surgery on those patients who have chronic pain who
      might need further debridement of the radius in the radial styloid, the proximal
      capitate, or evaluation of the integrity of the interposition.

PMID- 16274866
TI  - Radioscapholunate arthrodesis.
AB  - Although RSL fusion is a viable option for isolated radiocarpal arthritis, the
      enthusiasm for this procedure should be tempered with the reality that kinematics
      of the wrist is not entirely suited for independent midcarpal flexion and
      extension [10]. Limited wrist flexion and extension is expected following a
      successful RSL arthrodesis. The effects of imposed abnormal kinematics are
      further shown by the high incidence of RSL nonunions, occurrence of scaphoid
      fractures, and postoperative deterioration of the midcarpal joint [15,22]. In a
      young patient with posttraumatic arthritis or rheumatoid arthritis limited to the
      radiocarpal joint, however, RSL arthrodesis remains a viable alternative to
      complete wrist arthrodesis if the midcarpal joint is normal. Internal fixation
      with plates and screws and distal scaphoid excision are technical alternatives to
      consider when an RSL arthrodesis is performed.

PMID- 16274867
TI  - Ulnar impaction syndrome.
AB  - Although Palmer's classification of TFCC lesions differentiates post-traumatic
      central perforations (IA tears) from degenerative tears secondary to ulnocarpal
      impaction (IIC) [3], the distinction is not always clear clinically. In the final
      analysis, the literature suggests that as many as 25% of wrists with TFCC tears
      have residual symptoms following arthroscopic debridement alone [23], and it is
      likely that static or dynamic ul-nar positive variance plays a role [2,5,17,25].
      The authors' results suggest that combined arthroscopic TFCC debridement and
      wafer resection are feasible and efficacious as treatment for all stages of ulnar
      impaction syndrome. When class II A and B changes are observed, that is, when a
      TFCC perforation has not yet developed, the authors have observed favorable
      results in most patients following arthroscopic TFCC central disc excision and
      wafer resection as an alternative to ulnar shortening osteotomy [33] or open
      wafer excision [10].

PMID- 16274868
TI  - Management of the distal radioulnar joint in rheumatoid arthritis.
AB  - The DRUJ frequently is involved in RA and can be a source of major disability.
      Nonoperative treatment consists of adequate hand/occupational therapy, judicious
      splinting, and pharmacologic management. If unacceptable pain and dysfunction
      persists or if there is tendon rupture, surgery is indicated. Surgical treatment
      ranges from debridement and soft tissue balancing if the joint is preserved to
      osseous procedures ranging from Darrach resection, Sauve-Kapandji procedure,
      hemiresection, to distal ulna replacement. Tendon ruptures usually require tendon
      transfers. If an osseous procedure is required, the authors prefer the Sauve
      Kapandji procedure in the younger, active adult. Darrach distal ulna resection is
      recommended for the older, sedentary patient. For either procedure, if there is
      evidence of pre-existing radiocarpal instability, partial or total wrist
      arthrodesis or arthroplasty should bea concomitant procedure.

PMID- 16274869
TI  - Hemiresection arthroplasty of the distal radioulnar joint.
AB  - One of the critical requirements for this procedure to succeed is a functional
      TFCC structure. In rheumatoid arthritis or traumatic disruption of the DRUJ, the
      TFCC is unstable. If the TFCC can be reconstructed and DRUJ arthritis exists,
      this is the situation in which the hemiresection procedure excels. In the face of
      a normal DRUJ without arthritis, an ulnar shortening with a repair of the TFCC,
      if necessary, is the more appropriate procedure. The other caveat for this
      procedure to succeed is a careful preoperative plan to make sure stylocarpal
      impingement does not occur. The procedure does not restore stability in the
      unstable painful radioulnar joint; it simply substitutes a less painful
      instability. When correctly planned and performed the hemiresection interposition
      technique can be a good procedure in the arsenal of treatment for the DRUJ.

PMID- 16274870
TI  - Use of an ulnar head endoprosthesis for treatment of an unstable distal ulnar
      resection: review of mechanics, indications, and surgical technique.
AB  - Resection of the distal ulna for post-traumatic arthritis can lead to an unstable
      forearm joint through loss of the normal articular contact through the distal
      radioulnar joint and loss of soft tissue constraint. The resulting convergence
      instability can lead to residual pain, weakness, and loss of function.
      Restabilization of the forearm joint with implantation of an ulnar head
      endoprosthesis can re-establish the mechanical continuity of the forearm,
      reducing pain and improving strength and function. The anatomy,
      mechanics,rationale, and indications for surgical replacement of the distal ulna
      are presented. Important tenets of proper ulnar head implant insertion are given
      to provide a guide for use of the implant. Preliminary results after 2 years of
      clinical experience are encouraging.

PMID- 16274871
TI  - Total wrist arthroplasty.
AB  - Total wrist arthroplasty preserves motion and improves hand function for daily
      tasks and lower-demand vocational and a vocational activities. It is often
      preferable to fusion when both wrists are arthritic. Newer prosthetic designs
      provide a functional range of motion, better wrist balance,reduced risk of
      loosening, and better implant stability than older designs. The success of total
      wrist arthroplasty depends on appropriate patient selection, careful preoperative
      planning, and sound surgical technique.

PMID- 16274872
TI  - Wrist arthrodesis.
AB  - Wrist arthrodesis results in a high degree of patient satisfaction and
      predictable pain relief in most patients. Most patients are able to return to
      gainful employment, many without impairment. Some patients require restrictions
      and employment in a less strenuous occupation. Successful fusion rates have been
      reported in the vast majority of patients overall. Although the functional
      outcome is acceptable for most patients,some adaptation is necessary, because
      certain activities such as perineal care and manipulating the hand in tight
      spaces are difficult. Activities that require forceful gripping with the hand ina
      fully pronated or supinated position also may be difficult to accomplish.
      Preoperative counseling of the patient should include a candid discussion of the
      potential postoperative functional difficulties. The most common indication for a
      wrist arthrodesis is advanced symptomatic arthritis secondary to a degenerative,
      post-traumatic, inflammatory, or postinfectious condition. Wrist arthrodesis also
      may improve function, hygiene,and cosmesis in the patient who has a contracted or
      flail wrist associated with cerebral palsy, traumatic brain injury, or brachial
      plexus injury.Various techniques have been described for achieving a successful
      arthrodesis. The type of operative technique used depends on the underlying
      condition, quality of bone, presence of bi-lateral disease, condition of the
      remaining joints of the involved extremity, and surgeon's preference.
      Intramedullary rod or Steinman pin fixation has been successful in patients who
      have inflammatory arthritis. Dorsal plate and screw fixation is preferred for
      patients who have post-traumatic or degenerative arthrosis. Rigid fixation with a
      dorsal plate is advocated because of the ease of implant application, the high
      rates of fusion achieved, and the avoidance of prolonged postoperative cast
      immobilization. Precontoured low profile plates have been developed to position
      the hand appropriately and to minimize extensor tendon irritation. Controversy
      still exists as to the ideal position of the hand. Generally the wrist is placed
      in slight dorsiflexion and ulnar deviation to optimize power grip. In cases of
      bilateral involvement, the nondominant hand may be placed in 5 degrees -10
      degrees of flexion to better assist in such activities as perineal care.
      Complications are frequent but can be minimized with attention to detail and good
      surgical technique. Fortunately most complications are amenable to nonoperative
      treatment. Major complications include nonunion, deep wound infection, neuroma
      formation, DRUJ arthritis,ulnocarpal impaction, CTS, and painful retained
      hardware. Minor complications include hematoma formation, partial wound
      dehiscence, and transient paresthesias involving the radial, ulnar,or median
      nerves. Donor site morbidity remains a concern when the iliac crest is used.
      Complications include hematoma formation, infection, injury to the lateral
      cutaneous femoral nerve, and prolonged discomfort. Successful outcomes have been
      reported with the use of local autogenous cancellous bone graft from the distal
      radius metaphyseal region.

PMID- 16274873
TI  - New syntheses and potential antimalarial activities of new 'retinoid-like
      chalcones'.
AB  - A series of 'retinoid-like chalcones' and diverse derivatives relative to
      licochalcone A were synthesized from a new enaminone synthon. These syntheses
      occurred via a new aromatic annelation. These new derivatives have been tested in
      vitro as potential antimalarial agents. The 4-hydroxy-chalcone-like (compound 6a,
      derived from beta-ionone) exhibits a good and reproducible inhibitory effect on
      the in vitro culture of Plasmodium falciparum, with an IC 50 lower than 10 microM
      for inhibition of 3H-hypoxanthine uptake by parasites (respectively, 4.93 and
      8.47 microM for strains K1 and Thai).

PMID- 16274874
TI  - [Don't forget homocysteinemia's screening in young patients with arterial
      thrombosis].

PMID- 16274875
TI  - [Ankylosing spondylitis and osteoporosis].
AB  - PURPOSE: Ankylosing Spondylitis (AS) is an inflammatory rheumatism characterized
      by its disease course with flares leading to progressive ankylosis of the spine
      related to paravertebral ligamentous and discal structures ossification. AS
      patients suffer significantly more vertebral fractures than control groups. These
      fractures could affect cervical spine. They are due to either ankylosis-related
      flawed spine compliance or AS-induced osteoporosis. CURRENT KNOWLEDGE AND KEY
      POINTS: The physiopathology of this osteoporosis is multi-factorial, but
      essentially linked to AS-related inflammatory phenomenons. It is marked by
      reduced bone density (at lumbar spine and femoral neck), increased bone turnover
      (with increased urinary C-telopeptide cross-linked collagen type 1), but without
      any significant change in phosphocalcic blood parameters. Histological features
      are depressed bone formation, with either maintained or increased resorption.
      FUTURE PROSPECTS: The screening of this osteoporosis is based upon investigating
      people at risk (progressive inflammatory AS) using dual-energy x-ray
      absorptiometry and biochemical markers of bone turnover. Treatment is based upon
      a modulation of both inflammatory phenomenons and bone remodelling using
      bisphosphonates and anti-TNF alpha.

PMID- 16274876
TI  - Hemoglobin autoxidation and regulation of endogenous H2O2 levels in erythrocytes.
AB  - Red cells from mice deficient in glutathione peroxidase-1 were used to estimate
      the hemoglobin autoxidation rate and the endogenous level of H2O2 and superoxide.
      Methemoglobin and the rate of catalase inactivation by 3-amino-2,4,5-triazole (3
      AT) were determined. In contrast with iodoacetamide-treated red cells, catalase
      was not inactivated by 3-AT in glutathione peroxidase-deficient erythrocytes.
      Kinetic models incorporating reactions known to involve H2O2 and superoxide in
      the erythrocyte were used to estimate H2O2, superoxide, and methemoglobin levels.
      The experimental data could not be modeled unless the intraerythrocytic
      concentration of Compound I is very low. Two additional models were tested. In
      one, it was assumed that a rearranged Compound I, termed Compound II*, does not
      react with 3-AT. However, experiments with an NADPH-generating system provided
      evidence that this mechanism does not occur. A second model that explicitly
      includes peroxiredoxin II can fit the experimental findings. Insertion of the
      data into the model predicted a hemoglobin autoxidation rate constant of 4.5 x
      10(-7) s(-1) and an endogenous H2O2 and superoxide concentrations of 5 x 10(-11)
      and 5 x 10(-13) M, respectively, lower than previous estimates.

PMID- 16274877
TI  - Glycochenodeoxycholate plays a carcinogenic role in immortalized mouse
      cholangiocytes via oxidative DNA damage.
AB  - Bile acids have been suggested to be involved in biliary carcinogenesis, although
      the underlying mechanisms are yet to be established. The aim of this study was to
      investigate the carcinogenic effect of bile acids in the biliary tract in
      relation to oxidative stress. Immortalized mouse cholangiocytes were incubated
      with various bile acids, followed by measurement of reactive oxygen species (ROS)
      and the glutathione (GSH) level. As a marker of oxidative DNA damage, 8
      hydroxydeoxyguanosine (8-OHdG) expression in cholangiocytes was analyzed by flow
      cytometry. Then the expression of oxidative DNA repair enzymes in cholangiocytes
      was examined by real-time PCR. In addition, the long-term effect of bile acid
      induced oxidative DNA damage on cholangiocytes was investigated using a mouse
      oligo DNA microarray. It was found that glycochenodeoxycholate (GCDC) induced the
      generation of ROS and the depletion of GSH. In contrast, no marked changes were
      induced by the other bile acids. The percentage of 8-OHdG-positive cells was also
      increased by GCDC, but the expression of oxidative DNA repair enzymes was not up
      regulated. DNA microarray analysis showed marked changes of various genes
      associated with carcinogenesis (genes related to cell proliferation,
      angiogenesis, invasion, and metastasis). In conclusion, the long-term effect of
      oxidative DNA damage due to GCDC may promote carcinogenesis in the biliary tract.
      Furthermore, accumulation of 8-OHdG due to GCDC might contribute to the
      dysfunction of oxidative DNA repair enzymes.

PMID- 16274879
TI  - Characterization of Nrf2 activation and heme oxygenase-1 expression in NIH3T3
      cells exposed to aqueous extracts of cigarette smoke.
AB  - Cigarette smoke (CS) is a complex chemical mixture estimated to be composed of up
      to 5000 different chemicals, many of which are prooxidant. Here we show that, at
      least in vitro, the cellular response designed to combat oxidative stress
      resulting from CS exposure is primarily controlled by the transcription factor
      Nrf2, a principal inducer of antioxidant and phase II-related genes. The
      prominent role of Nrf2 in the cellular response to CS is substantiated by the
      following observations: In NIH3T3 cells exposed to aqueous extracts of CS (i)
      Nrf2 is strongly stabilized and becomes detectable in nuclear extracts. (ii)
      Nuclear localization of Nrf2 coincides with increased DNA binding of a putative
      Nrf2/MafK heterodimer to its cognate cis-regulatory site, i.e., the antioxidant
      responsive element (ARE). (iii) Studies on the regulatory elements of the
      oxidative stress-inducible gene heme oxygenase-1 (hmox1) using various hmox1
      promoter/luciferase reporter constructs revealed that the strong CS-dependent
      expression of this gene is primarily governed by the distal enhancers 1 ("E1")
      and 2 ("E2"), which both contain three canonical ARE-like stress-responsive
      elements (StREs). Notably, depletion of Nrf2 levels caused by RNA interference
      significantly compromised CS-induced hmox1 promoter activation, based on the
      distinct Nrf2 sensitivity exhibited by E1 and E2. Finally, (iv) siRNA-dependent
      knock-down of Nrf2 completely abrogated CS-induced expression of phase II-related
      genes. Taken together, these results confirm the outstanding role of Nrf2 both in
      sensing (oxidant) stress and in orchestrating an efficient transcriptional
      response aimed at resolving the stressing conditions.

PMID- 16274878
TI  - Nitrosative stress in an animal model of necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is a disease of newborns characterized by gut
      barrier failure. We reasoned that upregulation of inducible nitric oxide synthase
      (iNOS) may result in nitrosative stress and accumulation of nitroso species in
      the intestine. Newborn rats were either breast-fed (BF), or formula-fed and
      additionally subjected to hypoxia (FFH). At Day 4 after birth, the distal ilea
      were harvested and processed for Western blot analysis and measurement of NO
      related metabolites. While BF neonates showed normal morphology, FFH neonates
      developed signs of NEC by Day 4. These pathological changes correlated with
      upregulation of iNOS and increases in tissue nitrite, nitrosothiol, and
      nitrosamine concentrations. Enhanced nitroso levels were most prominent in the
      mucosal layers of the ileum and iNOS inhibition resulted in a significant
      decrease in both nitroso species and incidence of NEC. In contrast, increased
      nitrite levels were distributed evenly throughout the ileum and remained
      unchanged following iNOS inhibition. Similarly, specimens from NEC patients had
      higher intestinal levels of NO-related metabolites compared to non-NEC controls.
      This is the first report of tissue levels of nitroso species in the gut of an
      animal model of NEC and of human specimens. The results suggest that local
      nitrosative stress contributes to the pathology associated with NEC.
      Unexpectedly, the NO breakdown product nitrite, previously considered
      biologically inert, was found to be present throughout the ileal wall, suggesting
      that cellular NO metabolism is altered significantly in NEC. Whether nitrite
      plays a protective or deleterious role remains to be investigated.

PMID- 16274880
TI  - Macrophage uptake and recycling of ascorbic acid: response to activation by
      lipopolysaccharide.
AB  - To test whether ascorbic acid might be involved in the antioxidant defenses of
      inflammatory cells, we studied ascorbate uptake and recycling by quiescent and
      lipopolysaccharide-activated RAW264.7 murine macrophages. These cells
      concentrated ascorbate 100-fold in overnight culture, achieving steady-state
      concentrations of more than 10 mM at extracellular concentrations of 20-100 muM.
      This steep gradient was generated by high-affinity sodium-dependent ascorbate
      transport. The latter likely reflects function of the SVCT2 (SLC23A2), since this
      protein was detected on immunoblots. Dehydroascorbate, the two-electron oxidized
      form of ascorbate, was also taken up and reduced to ascorbate by the cells.
      Dehydroascorbate reduction required rapid recycling of GSH from GSSG by
      glutathione reductase. Activation of ascorbate-containing macrophages with
      lipopolysaccharide transiently depleted intracellular ascorbate without affecting
      GSH. Recovery of intracellular ascorbate required function of the SVCT2
      transporter, the activity of which was modestly enhanced by lipopolysaccharide.
      Lipopolysaccharide treatment nearly doubled intracellular GSH concentrations over
      2 h. Despite lipopolysaccharide-induced oxidant stress, this GSH increase was
      associated with a comparable increase in reduction of dehydroascorbate to
      ascorbate. These results show that macrophages maintain millimolar concentrations
      of ascorbate through function of the SVCT2 and that activated cells have an
      enhanced ability to transport and recycle ascorbate, possibly reflecting its role
      as an intracellular antioxidant.

PMID- 16274881
TI  - Microdialysis studies of extracellular reactive oxygen species in skeletal
      muscle: factors influencing the reduction of cytochrome c and hydroxylation of
      salicylate.
AB  - Identification and quantification of specific reactive oxygen species (ROS) is
      essential to allow greater understanding into the role that ROS play in tissues
      and extracellular fluids. Previous studies have examined the reduction of
      cytochrome c and the hydroxylation of salicylate to detect superoxide and
      hydroxyl activity, respectively, although the specificity of these assays has
      been the subject of debate. This study aimed to identify the factors influencing
      hydroxylation of salicylate and reduction of cytochrome c in microdialysates from
      skeletal muscle extracellular fluid. Mice were anesthetized and treated with
      either polyethylene glycol-tagged superoxide dismutase (PEG-SOD), desferrioxamine
      mesylate (desferal) or N(G)-nitro-l-arginine methyl ester (l-NAME). A further
      cohort of untreated mice was also studied. Microdialysis probes were placed into
      the gastrocnemius muscle and perfused with salicylate or cytochrome c prior to,
      during, and after a period of demanding electrically stimulated contractions.
      Microdialysates were analysed for the reduction of cytochrome c and hydroxylation
      of salicylate. Contractile activity was found to increase both the reduction of
      cytochrome c and the hydroxylation of salicylate in the microdialysates. The
      reduction of cytochrome c was greater in mice treated with l-NAME compared with
      control untreated mice and was attenuated in mice treated with PEG-SOD. The
      hydroxylation of salicylate was attenuated in mice treated with desferal while
      there was no effect of l-NAME compared with untreated mice. Data support the
      hypothesis that superoxide and hydroxyl radical activity are the major
      contributors to the reduction of cytochrome c and hydroxylation of salicylate
      respectively in microdialysates from skeletal muscle extracellular fluid and
      indicate that these ROS are increased by contractile activity in skeletal muscle
      extracellular fluid.

PMID- 16274882
TI  - A sensitive and selective assay for chloramine production by myeloperoxidase.
AB  - We describe a new assay for the chlorination activity of myeloperoxidase and
      detection of chloramines. Chloramines were detected by using iodide to catalyze
      the oxidation of either 3,3',5,5'-tetramethylbenzidine (TMB) or dihydrorhodamine
      to form strongly absorbing or fluorescent products, respectively. With TMB as
      little as 1 muM taurine chloramine could be detected. The sensitivity of the
      dihydrorhodamine assay was about 10-fold greater. The chlorination activity of
      myeloperoxidase was measured by trapping hypochlorous acid with taurine and
      subsequently using iodide to promote the oxidation reactions of the accumulated
      taurine chloramine. A similar approach was used to detect hypochlorous acid
      production by stimulated human neutrophils. Iodide-dependent catalysis
      distinguished N-chloramines from N-bromamines. This allows for discrimination
      between heme peroxidases that generate either hypochlorous acid or hypobromous
      acid. The assay has distinct advantages over existing assays for myeloperoxidase
      with regard to sensitivity, specificity, and its ease and versatility of use.

PMID- 16274883
TI  - Neurotoxicity of nitroxyl: insights into HNO and NO biochemical imbalance.
AB  - Nitroxyl anion (NO-), and/or its conjugate acid, HNO, may be formed in the
      cellular milieu by several routes under both physiological and pathophysiological
      conditions. Since experimental evidence suggests that certain reactive nitrogen
      oxide species can contribute significantly to cerebral ischemic injury, we
      investigated the neurotoxic potential of HNO/NO- using Angeli's salt (AS), a
      spontaneous HNO/NO(-)-generating compound. Exposure to AS resulted in a time- and
      concentration-dependent increase in neural cell death that progressed markedly
      following the initial exposure. Coadministration of the donor with Tempol (1 mM),
      a one-electron oxidant that converts NO- to NO, prevented its toxic effect, as
      did the concomitant addition of Fe(III)TPPS. Media containing various chelators,
      catalase, Cu/Zn superoxide dismutase, or carboxy-PTIO did not ameliorate AS
      mediated neurotoxicity, ruling out the involvement of transition metal complexes,
      H2O2, O2-, and NO, respectively. A concentration-dependent increase in
      supernatant protein 3-nitrotyrosine immunoreactivity was observed when cultures
      were exposed to AS under aerobic conditions, an effect lost in the absence of
      oxygen. A bell-shaped curve for augmented AS-mediated nitration was observed with
      increasing Fe(III)TPPS concentration, which contrasted with its linear effect on
      abating cytotoxicity. Finally, addition of glutamate receptor antagonists, MK-801
      (10 microM) and CNQX (30 microM) to the cultures abrogated toxicity when given
      during, but not following, AS exposure; as did pretreatment with the exocytosis
      inhibitor, tetanus toxin (300 ng/ml). Taken together, our data suggest that under
      aerobic conditions, AS toxicity is initiated via HNO/NO- but progresses via
      secondary excitotoxicity.

PMID- 16274884
TI  - Biological role of glutathione in nitric oxide-induced toxicity in cell culture
      and animal models.
AB  - Glutathione (GSH) plays an important role in cellular defense response in many in
      vitro and in vivo models. Here we investigated its role in NO()-induced toxicity
      in cell culture and mouse models. Wild-type (TK6) and p53-null (NH32) human
      lymphoblastoid cells were treated with NO(.) at a steady-state concentration of
      0.6 muM, similar to the level estimated to occur in inflamed tissues. In both
      cell types, GSH was depleted by this exposure in a dose- and time-dependent
      manner. Contrary to expectations, prior depletion of GSH by treatment with l
      buthionine-SR-sulfoximine did not potentiate NO(.)-induced cell killing or DNA
      deamination in TK6 cells. In activated RAW264.7 murine macrophages producing
      NO(.), intracellular GSH content did not change, although gamma-glutamate
      cysteine ligase was upregulated. NO(.) overproduction in RcsX lymphoma-bearing
      SJL mice resulted in significantly elevated GSH levels in various organs.
      Administration of the NO(.) synthase inhibitor N-methylarginine abolished the
      increase in GSH in these animals. Collectively, these data indicate a
      multifaceted and complex involvement of GSH in responses of cells and tissues to
      toxic levels of NO(.). NO(.) treatment effectively depleted GSH levels in human
      lymphoblastoid cells, but this alteration was not a critical initiating factor
      for NO(.)-mediated toxicity. Murine macrophages maintained GSH homeostasis when
      exposed to endogenously produced NO(.). In RcsX lymphoma-bearing mice,
      upregulation of de novo synthesis of GSH appeared to be a response to the toxic
      effects of NO(.).

PMID- 16274885
TI  - The role of oxidative stress in the modulation of aryl hydrocarbon receptor
      regulated genes by As3+, Cd2+, and Cr6+.
AB  - Heavy metals alter the capacity of AhR ligands to induce the bioactivating phase
      I and the detoxifying phase II xenobiotic-metabolizing enzymes but the
      mechanism(s) remain unknown. In the present study, we evaluated the role of
      As(3+)-, Cd(2+)-, and Cr(6+)-induced oxidative stress on the expression of
      Cyp1a1, Nqo1, and Gst ya in Hepa 1c1c7 cells. Both Cd2+ and Cr6+, but not As3+,
      increased the production of ROS. However, all metals increased cellular GSH
      content and heme oxygenase-1 mRNA levels. Although all three metals inhibited the
      induction of Cyp1a1 activity by TCDD, Cyp1a1 mRNA levels were potentiated. When
      cellular GSH was depleted with buthionine-(S,R)-sulfoximine (BSO), Cyp1a1 mRNA
      expression was further potentiated whereas Cyp1a1 activity was further inhibited.
      In parallel, pretreatment with the antioxidant N-acetylcysteine (NAC) did not
      alter Cyp1a1 mRNA expression but completely abrogated the inhibition of Cyp1a1
      activity induction by all three metals. On the other hand, all three metals,
      alone or in the presence of TCDD, enhanced Nqo1 and Gst ya mRNA levels and Nqo1
      activity. These effects were potentiated in the presence of BSO and abrogated
      with NAC. Our data clearly show that As(3+)-, Cd(2+)-, and Cr(6+)-induced
      oxidative stress modulates Cyp1a1 at transcriptional and posttranscriptional
      levels but induces Nqo1 and Gst ya at the transcriptional level.

PMID- 16274886
TI  - Oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine induces
      vascular endothelial superoxide production: implication of NADPH oxidase.
AB  - Modified low-density lipoprotein (LDL) induces reactive oxygen species (ROS)
      production by vascular cells. It is unknown if specific oxidized components in
      these LDL particles such as oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3
      phosphorylcholine (ox-PAPC) can stimulate ROS production. Bovine aortic
      endothelial cells (BAEC) were incubated with ox-PAPC (50 microg/ml). At 4 h, ox
      PAPC significantly enhanced the rate of O2- production. Pretreatment of BAEC in
      glucose-free Dulbecco's modified Eagle's medium plus 10 mM 2-deoxyglucose (2
      DOG), the latter being an antimetabolite that blocks NADPH production by the
      pentose shunt, significantly reduced the rate of O2- production. The intensity of
      NAD(P)H autofluorescence decreased by 28 +/- 12% in BAEC incubated with ox-PAPC
      compared to untreated cells, with a further decrease in the presence of 2-DOG. Ox
      PAPC also increased Nox4 mRNA expression by 2.4-fold +/- 0.1 while pretreatment
      of BAEC with the small interfering RNA (siNox4) attenuated Nox4 RNA expression.
      Ox-PAPC further reduced the level of glutathione while pretreatment with apocynin
      (100 microM) restored the GSH level (control = 22.54 +/- 0.23, GSH = 18.06 +/-
      0.98, apocynin = 22.55 +/- 0.60, ox-PAPC + apocynin = 21.17 +/- 0.36 nmol/10(6)
      cells). Treatment with ox-PAPC also increased MMP-2 mRNA expression accompanied
      by a 1.5-fold increase in MMP-2 activity. Ox-PAPC induced vascular endothelial
      OO2-(.) production that appears to be mediated largely by NADPH oxidase activity.

PMID- 16274887
TI  - Repression by oxidative stress of iNOS and cytokine gene induction in macrophages
      results from AP-1 and NF-kappaB inhibition mediated by B cell translocation gene
      1 activation.
AB  - Previously, we reported that oxidative stress caused by sulfur amino acid
      deficiency (SD) induces B cell translocation gene-1 (Btg-1), which belongs to the
      Apro family, in hepatocytes. In view of the impairment of immune function by
      protein restriction that causes SD, this study investigated whether SD or other
      oxidative stress inhibits iNOS and cytokine expression and induces Btg-1 in
      macrophages and explored the causal relationship of Btg-1 induction and
      repression of the genes. When macrophages were incubated in sulfur amino acid
      deprived medium, lipopolysaccharide induction of iNOS, TNFalpha, IL-1beta, and IL
      6 was significantly decreased compared to control. Because AP-1 and NF-kappaB are
      the common transcription factors that regulate the genes encoding iNOS and
      cytokines, we examined AP-1 and NF-kappaB DNA binding activities and
      transactivation of the iNOS gene containing the DNA binding elements. Induction
      of the reporter gene pGL-miNOS-1588 comprising the -1.6 kb iNOS promoter in
      lipopolysaccharide-activated macrophages was inhibited 30-70% by SD or treatment
      with pro-oxidants, including tert-butylhydroxyquinone, buthionine sulfoximine,
      and 3-morpholinosydnonimine. Oxidative stress increased Btg-1 mRNA. SD-induced
      oxidative stress activated Btg-1 in macrophages, as evidenced by nuclear
      translocation of endogenous or green fluorescent protein-tagged Btg-1, which
      localized in the cytoplasm in the resting state. Expression of Btg-1 inhibited
      lipopolysaccharide-inducible AP-1 and NF-kappaB activities, repressing
      transactivation of the target gene pGL-miNOS-1588. These results provide evidence
      that oxidative stress induced by SD or pro-oxidants inhibits the expression of
      iNOS and cytokines in macrophages with Btg-1 activation and that the gene
      repression by oxidative stress may result from Btg-1-mediated inhibition of AP-1
      and NF-kappaB activities.

PMID- 16274888
TI  - Reduction of viral loads by multigenic DNA priming and adenovirus boosting in the
      SIVmac-macaque model.
AB  - In this study, we investigated the ability of a multigenic SIV DNA
      prime/replication-defective adenovirus serotype 5 (rAd/SIV) boost regimen to
      induce SIV-specific immune responses and protection against intrarectal challenge
      with SIVmac251 in rhesus macaques. Four rhesus macaques were immunized
      intramuscularly three times at 8-week intervals with SIV DNA vaccine and boosted
      once with rAd/SIV vaccine Four control macaques received the same amount of mock
      plasmid DNA and mock adenovirus vector. While the SIV DNA vaccine included
      plasmids expressing a mutated human IL-12 gene (IL-12N222L) as well as SIVmac239
      structural and regulatory genes, the rAd/SIV vaccine contained rAd vectors
      expressing SIVmac239 genes only. Immunization with SIV DNA vaccine alone induced
      SIV-specific IFN-gamma ELISPOT responses in only two of four vaccinated macaques,
      whereas all animals developed SIV-specific T-cell responses and Env- and Tat
      specific antibody responses following the rAd/SIV vaccine boost. Upon intrarectal
      challenge with pathogenic SIVmac251, strong anamnestic Env-specific binding and
      neutralizing antibody responses were detected in the vaccinated macaques.
      Overall, the immunized macaques had lower peak and set-point viral loads than
      control macaques, suggesting that the induced immune responses play a role in the
      control of viremia. In addition, the loss of CD4+ T cells was delayed in the
      vaccinated macaques after challenge. These results indicate that the multigenic
      DNA prime-adenovirus boost immunization may be a promising approach in developing
      an effective AIDS vaccine.

PMID- 16274889
TI  - Burst fracture of the spine involving vertebrae presenting no other lesions: the
      role of vertebroplasty.
AB  - We report our experience on percutaneous vertebroplasty performed on five
      patients who presented with history of trauma to the spine and secondary burst
      fracture, but with stable fractures, and on whom the medical and orthopedical
      therapies had been unsuccessful in the relief of the intractable pain and in the
      treatment of their functional status. Four cases have benefitted from the
      intervention, with complete disappearance of the symptomatology in two and
      incomplete in the other two. In one case, the improvement in the persistent
      painful symptoms was of no significance. Controls by computed tomography (CT).
      Which were performed after 3 months showed a satisfactory consolidation of the
      fractured vertebrae.

PMID- 16274890
TI  - Computed-tomographic features of invasive lobular carcinoma.
AB  - We retrospectively analyzed contrast-enhanced computed tomography (CE-CT)
      findings in 18 patients with pure invasive lobular carcinoma (ILC). The features
      were divided into five types: an ill-defined and inhomogeneous mass with or
      without regional heterogeneous enhancement, a spiculated inhomogenous mass, a
      regional heterogeneous enhancement, and a normal finding. The correlation between
      tumor size on pathological examination was better with size estimation on CE-CT
      than that on mammography and sonography. CE-CT may provide additional information
      on the characteristics and extent of this carcinoma.

PMID- 16274891
TI  - Concordance of mammographic classifications of microcalcifications in breast
      cancer diagnosis: Utility of the Breast Imaging Reporting and Data System (fourth
      edition).
AB  - The purpose of this study is to evaluate breast microcalcifications according to
      morphology, distribution, level of suspicion, Breast Imaging Reporting and Data
      System (BI-RADS; fourth edition) final assessment, and recommendation categories
      and to assess positive predictive values and interobserver variability among
      three observers in 83 patients in whom biopsies had been performed. Although
      there is considerable inconsistencies in agreement between observers in the
      classification of microcalcifications, the usage of BI-RADS (fourth edition), in
      which the explicit recommendations for the description of the lesions was made,
      succeeds in the evaluation of microcalcifications.

PMID- 16274892
TI  - Radiology-Pathology conference: papillary carcinoma of the breast.
AB  - Papillary carcinoma of the breast is a rare breast carcinoma. It can be
      classified into invasive and noninvasive types. It can also be classified into
      intracystic and intraductal papillary carcinoma. Different radiological features
      are found to be associated with different histological types. Pitfalls are found
      to be associated with fine needle aspiration and core biopsy in the evaluation of
      papillary lesions. It is therefore important for radiologists to diagnose
      papillary carcinoma for proper management of the patients.

PMID- 16274893
TI  - Diagnosis of malpositioned chest tubes after emergency tube thoracostomy: is
      computed tomography more accurate than chest radiograph?
AB  - OBJECTIVE: The aim of this study was to compare the accuracy between computed
      tomography (CT) and frontal chest radiography in the diagnosis of malpositioned
      chest tubes (MCT). MATERIALS AND METHODS: CT scans positive for MCT between March
      2000 and March 2004 were reviewed. Two radiologists assessed for intra- and
      extrathoracic locations of MCT in CT studies. Two physicians who were blinded to
      the results of CT scans assessed the frontal chest radiographs for location of
      chest tubes, within the pleural space or outside pleural space. The results of CT
      were then compared with the results of frontal chest radiographs. Medical records
      were also reviewed for function of the chest tubes and any complications induced
      by MCT. RESULTS: CT revealed 28 MCT among the 76 chest tubes that were placed in
      54 patients. Among the 28 MCT detected by CT, 23 tubes were in the intrathoracic
      location (20 intraparenchymal; 3 intrafissural) and 5 tubes were in the
      extrathoracic location (4 in mediastinum; 1 in chest wall). Frontal chest
      radiographs only revealed six MCT. Among 28 MCT, 16 sufficient, 8 insufficient,
      and 4 indeterminate functions of the chest tubes were noted from medical charts.
      One patient complicated with lung abscess, four patients had suffered pleural
      empyema, and one patient suffered active lung parenchymal bleeding, resulting
      from MCT. CONCLUSIONS: CT is more accurate than chest radiograph for the
      diagnosis of MCT. For selected patients with inadequacy drainage of the tubes and
      when chest radiograph is noncontributory, CT scan is recommended to clarify the
      exact location of chest tubes.

PMID- 16274894
TI  - Chronic, reactive conditions of the oral cavity simulating mucosal carcinomas: CT
      and MR imaging findings with pathologic correlation in five patients.
AB  - To investigate the radiologic and pathologic findings of chronic, inflammatory,
      reactive conditions of the oral cavity, which clinically and radiologically
      simulate mucosal malignancy, computed tomography (CT; n=4) and magnetic resonance
      (MR; n=2) images, as well as surgical specimens, obtained from five patients with
      surgically proved, chronic inflammatory mass of the oral cavity were
      retrospectively reviewed. All patients had a palpable mass or ulcerative lesion
      in the oral cavity. On CT and MR images, all three lesions in the oral tongue and
      one lesion in the retromolar trigone were seen as a superficial, ill-marginated,
      well-enhancing ellipsoid or focal soft tissue mass. Pathologic examinations
      revealed various depths and degrees of acute and chronic inflammation,
      granulation tissue, and fibrosis in the subepithelial stroma, accompanied by
      pseudoepitheliomatous hyperplasia in these four patients. In the remaining one
      patient with lesion in the hard palate, CT showed a relatively well-marginated,
      well-enhancing soft tissue mass, which histologically proved to be irritation
      fibroma. Neither clinical nor radiologic manifestations could afford clues to
      make the correct diagnosis, which therefore should rely on histology. Some forms
      of chronic, inflammatory, reactive conditions of the oral cavity are nearly
      indistinguishable from the malignant tumors both clinically and radiologically.
      Knowledge of this entity may obviate the unnecessary and somewhat disfiguring
      operation.

PMID- 16274895
TI  - Magnetic resonance imaging of prostate carcinoma using phased-array coils:
      therapeutic effect and recurrence.
AB  - Magnetic resonance imaging with phased-array coils was performed in patients with
      prostate carcinoma before and after hormonal therapy, radiation therapy or
      radical prostatectomy to evaluate therapeutic effect and recurrence. After
      hormonal therapy, the prostate gland, seminal vesicle and primary site of tumor
      usually decrease in size with variable T2 hypointensity. Recurrent or residual
      tumors after hormonal therapy usually represent T2 hyperintense lesions compared
      to the hypointensity of the surrounding tissues. Changes of metastatic sites
      after therapy were also demonstrated.

PMID- 16274896
TI  - Acquired complicated diverticulum of the ileum.
AB  - The complicated diverticula of the ileum are a rare cause of an acute abdomen. We
      report on a case in whom the CT imaging leads to the surgical removal of the
      ileocecal segment.

PMID- 16274897
TI  - Solitary plasmacytoma of the sacrum. Radiologic findings of three cases.
AB  - We report the radiologic findings from three cases of solitary plasmacytoma (SP)
      of the sacrum. Common findings included lytic changes on computed tomography (CT)
      and relatively low signal intensity on T2-weighted magnetic resonance (MR)
      images, with intense enhancement after contrast administration. All cases showed
      infiltrating and slightly expansive growth, but the sacral structure was
      generally maintained. These radiologic findings may be of utility when generating
      a differential diagnosis of a solitary sacral tumor.

PMID- 16274898
TI  - Anterior coloboma with macrophthalmos and cyst: MR findings.
AB  - Coloboma is one of the congenital ocular malformations presenting important
      diagnostic and therapeutic problems, especially in infants. Coloboma can be
      associated with microphthalmia frequently and macrophtalmia rarely. However, the
      association of coloboma, macrophthalmia, and orbital cyst was not reported
      previously in the literature. A case of coloboma associated with macrophtalmia
      and cyst was presented, and MR findings of this anomaly was defined with emphasis
      to the importance of radiologic examinations in the diagnosis of some congenital
      ocular malformations.

PMID- 16274899
TI  - MRI features of a pancreatic schwannoma.
AB  - A case of a pancreatic schwannoma is presented. The patient, a previously healthy
      woman, is hospitalized with the diagnosis of purulent pleuritis. Ultrasonography
      (US) of the abdomen shows a 3-cm mass in the head of the pancreas. Magnetic
      resonance imaging (MRI) reveals, in T1-weighted sequences, the mass to be
      hypointense, and an early and persistent enhanced signal is noted following the
      administration of gadolinium. In T2-weighted fat saturation sequences, the lesion
      appears markedly hyperintense. A duodenopancreatotomy is performed, and the
      pathologic specimen demonstrates a schwannoma of the pancreas with Antoni A
      pattern.

PMID- 16274900
TI  - Tension pyopneumothorax.
AB  - Tension pyopneumothorax is a rare complication of pneumonia and subpleural
      abscess eroding into the pleural space. We present a case of tension
      pyopneumothorax in a drug addict. Successful treatment consisted of pleural
      drainage and parenteral antibiotics. The presence of an air-fluid level
      accompanying tension pneumothorax on chest radiograph should alert the physician
      to the possibility of this emergency condition.

PMID- 16274901
TI  - Analysis of temperature influences on the amplitude-frequency characteristics of
      Rn gas concentration.
AB  - The ventilation mechanism of Rn gas in underground environments is considered.
      Ventilation plays an important role in influencing the variability (harmonics) of
      Rn gas in the porous space below the earth's surface. We propose a new physical
      environmental model of relating Rn gas concentrations to air temperature
      variations at the earth's surface. Applicability of this model was tested after
      searching for Rn gas indicators of geodynamic processes in two underground
      tunnels in central and southern Israel. The theoretical estimation of Rn gas
      concentrations shows a good agreement with the observed values. We demonstrate
      the possibility of Rn gas anomalies being caused by atmospheric temperature
      variations and the necessity to take these effects into account when
      investigating geodynamic processes.

PMID- 16274902
TI  - 222Rn as indicator of atmospheric turbulence: measurements at Lake Maggiore and
      on the pre-Alps.
AB  - Radon concentration measurements in atmosphere were taken in years from 1997 to
      1999 in Milan and at pre-alpine sites located north of Lombardy. In this paper
      the results of measuring campaigns and a comparison of radon levels observed in
      the hilly area north of the town and on the pre-Alps are reported. The general
      criteria of the measurements and the interpretative models of radon concentration
      are presented. The Lake Maggiore area shows evidence of a great nocturnal
      stability and frequent formation of Nocturnal Stable Layer. The peculiar findings
      in the high altitude stations confirm the use of radon as an indicator of
      atmospheric dispersion of pollutants in an area with complex orography. The
      afternoon minimum values are concordant for the different stations: this implies
      a remixing in afternoon hours over the whole area investigated.

PMID- 16274903
TI  - Shoulder movements during the initial phase of learning manual wheelchair
      propulsion in able-bodied subjects.
AB  - BACKGROUND: The kinetics and kinematics of the glenohumeral joints, and shoulder
      muscles activities during the initial phase of learning wheelchair propulsion by
      individuals with paraplegia have been partially described. But no studies carry
      out the kinematics of the upper-limb during the learning of non-constrained open
      field locomotion with a wheelchair. METHODS: Ten subjects with no manual
      wheelchair experience propelled themselves repetitively straight ahead along an
      11m linear path. Upper-limb segment orientations were measured with an
      electromagnetic system. Angular displacements of joints were determined using a
      standardized protocol [Wu, G., Van der Helm, F.C.T., Veeger, H.E.J., Makhsous,
      M., Van Roy, P., Anglin, C., Nagels, J., Karduna, A.R., McQuade, K., Wang, X.,
      Wernerl, F.W., Buchholzm, B., 2005. ISB recommendation on definitions of joint
      coordinate systems of various joints for the reporting of human joint motion-
      Part II: shoulder, elbow, wrist and hand. J. Biomech. 38(5), 981-992] and a
      modeling method [Biryukova, E.V., Roby-Brami, A., Frolov, A.A., Mokhtari, M.,
      2000. Kinematics of human arm reconstructed from spatial tracking system
      recordings. J. Biomech. 33, 985-995]. FINDINGS: A full 3-D scapular motion
      description was obtained that allowed us to measure the mean amplitudes of
      rotation for the nine degrees of freedom of our model. The change in the
      propulsion pace and the repetition of trials induced a general increase of
      amplitudes of joint rotations that can explain the increase of velocity among
      trials. INTERPRETATION: We did not observe a freezing of any DOF as predicted by
      Bernstein's theory of motor learning, but the increase in joint movement
      amplitudes could correspond to his "unfreezing of DOF" stage. This non-respect of
      Bernstein's theory could originate in the relative simplicity of the task.

PMID- 16274904
TI  - The mechanics of landing when stepping down in unilateral lower-limb amputees.
AB  - BACKGROUND: The ability to successfully negotiate stairs and steps is an
      important factor for functional independence. While work has been undertaken to
      understand the biomechanics of gait in lower-limb amputees, little is known about
      how amputees negotiate stairs and steps. This study aimed to determine the
      mechanics of landing in unilateral lower-limb amputees when stepping down to a
      new level. A secondary aim was to assess the effects of using a shank-mounted
      shock-absorbing device (Tele-Torsion Pylon) on the mechanics of landing. METHODS:
      Ten unilateral amputees (five transfemoral and five transtibial) and eight able
      bodied controls performed single steps down to a new level (73 and 219 mm).
      Trials were repeated in amputees with the Tele-Torsion Pylon active and inactive.
      The mechanics of landing were evaluated by analysing peak limb longitudinal
      force, maximal limb shortening, lower extremity stiffness, and knee joint angular
      displacement during the initial contact period, and limb and ankle angle at the
      instant of ground-contact. Data were collected using a Vicon 3D motion analysis
      system and two force platforms. FINDINGS: Amputees landed on a straightened and
      near vertical limb. This limb position was maintained in transfemoral amputees,
      whereas in transtibial amputees knee flexion occurred. As a result lower
      extremity stiffness was significantly greater in transfemoral amputees compared
      to transtibial amputees and able-bodied controls (P<0.001). The Tele-Torsion
      Pylon had little effect on the mechanics of landing in transtibial amputees, but
      brought about a reduction in lower extremity stiffness in transfemoral amputees
      (P<0.05). INTERPRETATION: Amputees used a stepping strategy that ensured the
      direction of the ground reaction force vector was kept anterior of the knee joint
      centre. Using a Tele-Torsion Pylon may improve the mechanics of landing during
      downward stepping in transfemoral amputees.

PMID- 16274905
TI  - Bilateral and unilateral shoulder girdle kinematics during humeral elevation.
AB  - BACKGROUND: Due to the complexity of the shoulder mechanism, shoulder complex
      models to describe the reachable workspace generally lack information on shoulder
      girdle kinematics. METHODS: Shoulder girdle kinematic data were recorded using an
      optoelectronic tracking device. Five male and five female healthy subjects
      performed bilateral and unilateral humeral elevation in four planes anterior and
      posterior to the body. RESULTS: Bilateral and unilateral shoulder girdle
      kinematics during humeral elevation were substantially different. Bilateral
      shoulder movements led to a smaller workspace and larger contractions
      elongations. Similar patterns of shoulder girdle elevation and retraction
      accompanying humeral elevation appeared in all measured planes, known as the
      shoulder rhythm. The shoulder girdle changes its length as a quadratic function
      during humeral elevation. The shoulder girdle angular motion range is the largest
      in the non-elevated humerus position, it is reduced during humeral elevation and
      halves in humerus maximal elevated position. CONCLUSIONS: To describe motions of
      the shoulder complex, a model is proposed composed of an inner joint representing
      shoulder girdle joints and an outer joint representing the glenohumeral joint.
      RELEVANCE: The proposed model offers the possibility to compare movement of
      shoulders with disorders to a normal pattern. It can also provide a basis for
      shoulder complex kinematic modeling, biomechanical analysis, motion
      characteristics and exact calculation of the humerus reachable workspace.

PMID- 16274906
TI  - Rotation sequence as an important factor in shoulder kinematics.
AB  - BACKGROUND: The International Society of Biomechanics has proposed a
      standardization recommendation for motion recordings of the upper extremity
      defining the set of bony landmarks, local coordinate systems and joint coordinate
      systems. The aim of our study was to verify the clinical interpretation of the
      proposed rotation sequence for the glenohumeral joint and to compare it with
      other sequences. METHODS: Fifteen glenohumeral movements in their maximal ranges
      were tested on five healthy subjects. The movements were separated into five
      groups (flexion, extension, abduction, horizontal flexion and circumduction) with
      three humeral rotation positions (full external, full internal and neutral). Four
      glenohumeral rotation sequences were constructed using YXY, YXZ, ZXY and XZY
      orders and angle amplitudes were examined in terms of gimbal lock and amplitude
      coherence. FINDINGS: The results of the gimbal lock incidence and amplitude
      coherence should be taken into account together. Therefore, the suitable rotation
      sequences for all rotation variations of abduction and extension were found and
      no tested rotation sequence was found to be clinically interpretable for all
      tested movements. INTERPRETATION: Before glenohumeral three-dimension experiments
      the choice of the rotation sequence should be made in agreement with the no
      gimbal lock incidence and amplitude interpretability of the performed movements.

PMID- 16274907
TI  - An exploration of the relationship between adsorption and bioavailability of
      pesticides in soil to earthworm.
AB  - A study was conducted to determine the adsorption/desorption of butachlor,
      myclobutanil and chlorpyrifos on five soils using a batch equilibration technique
      and to study the relationship between bioavailability to Allolobophora caliginosa
      and the adsorption/desorption of these three pesticides. The results showed that
      the adsorption/desorption processes of the tested compounds were mainly
      controlled by soil organic matter content (OM) and octanol/water-partitioning
      coefficient (K(ow)), and that the bioavailability of the pesticides was dependent
      on characteristics of pesticides, properties of soils, and uptake routes of
      earthworms. Bioconcentration of butachlor and myclobutanil was negatively
      correlated with Freundlich adsorption constant K(af) and K(df). However, only a
      slightly positive correlation between bioconcentration and K(af) and K(df) was
      observed for chlorpyrifos due to its high affinity onto soil.

PMID- 16274908
TI  - The relationship among microsomal enzyme induction, liver weight, and
      histological change in cynomolgus monkey toxicology studies.
AB  - The purpose of this investigation was to examine the relationship among hepatic
      microsomal enzyme induction, liver weight, histological evidence of hepatic
      injury, and serum clinical chemistry markers of hepatic origin in the cynomolgus
      monkey. We report here the results from independent toxicology studies for 10
      investigative drug candidates representing four therapeutic classes. Study
      conditions were selected to elicit target organ toxicity. We found that six of
      the 10 compounds altered cytochrome P450-associated activities in both male and
      female monkeys, two in females only, and one altered similar activities in males
      only. Frequently, significant treatment-related elevations in NADPH cytochrome c
      reductase and ethylmorphine N-demethylase were noted. When the results from all
      10 studies were pooled, 14 cytochrome P450-associated activities were
      significantly increased and five were decreased in males compared to 15
      significantly increased and three decreased in the females. Treatment-associated
      liver weight increases were noted in four studies. Except for hepatocellular
      hypertrophy in one study, no significant treatment-related microscopic changes in
      liver and no elevations of serum biomarkers commonly associated with liver
      toxicity were observed in any of the studies that demonstrated significant
      hepatic enzyme induction. Compared to parallel rat studies, one compound was an
      inducer only in monkeys and one was an inducer only in rats. Significant
      elevations of microsomal drug-metabolizing enzymes in the cynomolgus monkey liver
      are not accompanied by substantial hepatic changes except for hepatomegaly. These
      alterations in the hepatic drug-metabolizing enzyme system were benign based the
      absence of histopathological lesions and serum biomarkers of hepatobiliary
      toxicity.

PMID- 16274909
TI  - Stair climbing detection during daily physical activity using a miniature
      gyroscope.
AB  - A new method of monitoring physical activity that is able to detect walking
      upstairs using a miniature gyroscope attached to the shank is presented. Wavelet
      transformation, in conjunction with a simple kinematics model, was used to detect
      toe-off, heel-strike and foot-flat, as well cycles corresponding to stair ascent.
      To evaluate the system, three studies were performed. The method was first tested
      on 10 healthy young volunteer subjects in a gait laboratory where an ultrasonic
      motion system was used as a reference system. In the second study, the system was
      tested on three hospitalized elderly people to classify walking upstairs from
      walking downstairs and flat walking. In the third study, monitoring was performed
      on seven patients with peripheral vascular disease for 60min during their daily
      physical activity. The first study revealed a close relationship between the
      ambulatory and the reference systems. Compared to the reference system, the
      ambulatory system had an overall sensitivity and specificity of 98% and 97%,
      respectively. In the second study, the ambulatory system also showed a very high
      sensitivity (>94%) in identifying a 50 stairs ascent from walking on the flat and
      walking downstairs. Finally, compared with visual surveillance, we observed a
      relatively high accuracy in identifying 196 walking upstairs cycles through daily
      physical activity in the third study. Our results demonstrated a reliable
      technique of measuring walking upstairs during physical activity.

PMID- 16274910
TI  - Postural activity of the abdominal muscles varies between regions of these
      muscles and between body positions.
AB  - The abdominal muscles have an important role in control and movement of the
      lumbar spine and pelvis. Given there is new evidence of morphological and
      functional differences between distinct anatomical regions of the abdominal
      muscles, this study investigated whether there are regional differences in
      postural activity of these muscles and whether recruitment varies between
      different body positions. Eleven subjects with no history of low back pain that
      affected function or for which they sought treatment participated in the study.
      Electromyographic (EMG) activity of the upper, middle and lower regions of
      transversus abdominis (TrA), the middle and lower regions of obliquus internus
      abdominis (OI) and the middle region of obliquus externus abdominis (OE) was
      recorded using intramuscular electrodes. All subjects performed rapid, unilateral
      shoulder flexion in standing and six subjects also moved their upper limb in
      sitting. There were regional differences in the postural responses of TrA with
      limb movement. Notably, the onset of EMG of the upper region was later than that
      of the lower and middle regions. There were no differences in the EMG onsets of
      lower and middle TrA or OI. The postural responses of the abdominal muscles were
      also found to differ between body positions, with recruitment delayed in sitting
      compared to standing. This study showed that there is regional differentiation in
      TrA activity with challenges to postural control and that body position
      influences the postural responses of the abdominal muscles. These results may
      reflect variation in the contribution of abdominal muscle regions to stability of
      the trunk.

PMID- 16274911
TI  - Effect of painful keratoses debridement on foot pain, balance and function in
      older adults.
AB  - BACKGROUND: Painful feet in older people can detrimentally affect balance and are
      a risk factor for falls. Pain is often associated with plantar hyperkeratoses,
      which are easily treated by podiatrists. Currently, there is no data defining the
      effect this treatment has on balance or functional ability. OBJECTIVE: To
      determine the effects of scalpel debridement of painful plantar hyperkeratoses on
      pain, balance and functional ability in older people aged 65 years and over.
      SUBJECTS: Nineteen men and women aged 65-84 years (mean age 72, standard
      deviation 5.6). METHODS: Pain resulting from plantar hyperkeratoses was measured
      using a visual analogue scale. Static balance and functional ability were
      measured using tests of postural sway, co-ordinated stability and timed walking
      and stepping tests. Painful plantar hyperkeratoses were debrided with a scalpel
      then all tests were repeated, immediately and 7 days later. RESULTS: Following
      scalpel debridement, pain levels (sensory and afferent) were significantly
      reduced (P<0.0001) and functional ability was significantly increased (P<0.0001).
      There was no change in static balance ability. One week after debridement the
      improved performance in functional ability tests was maintained. CONCLUSIONS:
      Debridement of painful plantar hyperkeratoses reduces pain and improves
      functional ability in older people. Its effect on static balance was
      inconclusive.

PMID- 16274912
TI  - Evaluation of head-to-trunk control in whiplash patients using digital
      CranioCorpoGraphy during a stepping test.
AB  - We used digital-CranioCorpoGraphy (dCCG) to document whiplash effects on head-on
      trunk stabilization while subjects walked on the spot (Fukuda test). Twenty-five
      healthy subjects were compared with 33 whiplash patients. Whiplash patients were
      classified as chronic (more than 6 months after injury) and recent (less than 6
      months after injury). Clear differences between healthy subjects and patients
      were seen and three different strategies were detected. Pattern A appeared
      similar to normals but quantitative analysis showed significant differences with
      paradoxical head over-stabilization (collar-effect); pattern B decreased head
      stability; pattern C decreased head stabilization with reduced displacements of
      the body. Due to the complexity of the data analyzed for each marker, a
      coefficient of performance (CP) was calculated to simplify the cut-off between
      normal and pathological tests. CP clearly identified an abnormal stepping
      pattern. Our findings indicate that firstly dCCG identified a specific vestibular
      task in whiplash patients, secondly whiplash did not always provoke vestibular
      involvement and thirdly dCCG could be a tool to discriminate patients with and
      without vestibular involvement after whiplash.

PMID- 16274913
TI  - Validity of the GAITRite walkway system for the measurement of averaged and
      individual step parameters of gait.
AB  - This study compared individual step and averaged spatial and temporal gait
      parameters measured with an instrumented walkway system (GAITRite) with a three
      dimensional motional analysis system (Vicon-512). Ten subjects aged 54-83 years
      (mean 66.5 years) who had undergone knee replacement surgery participated.
      Subjects walked across the GAITRite walkway at self-selected comfortable and fast
      speeds at the same time as the Vicon system recorded the motion of reflective
      markers attached to the subjects' shoes. Walking speed, cadence, step length and
      step time variables, averaged across one walk for both systems, showed an
      excellent level of agreement with intra-class correlation coefficients (ICCs)
      between 0.92 and 0.99 and repeatability coefficients (RCs) between 1.0% and 5.9%
      of mean values. Step length and step time variables recorded for each footstep
      also showed good agreement between the systems at both comfortable and fast
      speeds (ICCs between 0.91 and 0.99; RCs between 2.6% and 7.8%). Frequency
      distributions showed that individual step values were within 1.5 cm and 0.02 s on
      the majority (80-94%) of occasions. These data indicate that the GAITRite system
      is a valid tool for measuring both averaged and individual step parameters of
      gait. It is also valid for use in older subjects following knee joint replacement
      surgery.

PMID- 16274914
TI  - Age-related changes in human postural control of prolonged standing.
AB  - The aim of this study was to characterize prolonged standing and its effect on
      postural control in elderly individuals in comparison to adults. It is unknown
      how elderly individuals behave during prolonged standing and how demanding such a
      task is for them. We recorded the center of pressure (COP) position of 14 elderly
      subjects and 14 adults while they performed prolonged standing (30 min) and quiet
      stance tasks (60s) on a force plate. The number and amplitude of the COP
      patterns, the root mean square (RMS), speed, and frequency of the COP sway were
      analyzed. The elderly subjects were able to stand for prolonged periods but they
      produced postural changes of lesser amplitude and a decreased sway during the
      prolonged standing task. Both the adults and the elderly subjects were influenced
      by the prolonged standing task, as demonstrated by their increased COP RMS and
      COP speed in the quiet standing trial after the prolonged standing task, in
      comparison to the trial before. We suggest that the lack of mobility in elderly
      subjects may be responsible for the observed sub-optimal postural changes in this
      group. The inability of elderly individuals to generate similar responses to
      adults during prolonged standing may contribute to the increased risk of falls in
      the older population.

PMID- 16274915
TI  - Efficiency of work production by spastic muscles.
AB  - The present study compared the muscular efficiency in spastic and healthy lower
      limbs producing the same mechanical work. Sixteen chronic post-stroke hemiparetic
      and spastic patients and 14 age-matched healthy subjects were submitted to a
      submaximal stepwise exercise testing on a bicycle ergometer, pedalling with only
      one lower limb. Net energetic expenditure was computed from oxygen consumption
      above resting values. Electrical activity of antagonistic muscles in the thigh
      and in the shank was recorded and co-contraction was defined as the percentage of
      the pedalling cycle when antagonistic muscles were activated simultaneously. The
      efficiency was calculated as the ratio between the mechanical work done on the
      ergometer and the net energetic expenditure. Spasticity was quantitatively
      evaluated by measuring passive ankle plantar flexor muscle stiffness. The working
      capacity of the patients' paretic lower limb was very low (<40W). The energy
      expenditure increased linearly as a function of work intensity, without
      statistical difference between the patients paretic lower limb (PPL), the
      patients healthy lower limb (PHL) and the healthy subjects lower limb (HSL).
      Shank co-contraction was 2.9 times greater in PPL (p<0.05) and 2.3 times greater
      in PHL (p<0.05) than in HSL. Thigh co-contraction was also 1.8 times greater in
      PPL than in HSL (p<0.05). The ankle plantar flexor muscle stiffness was
      statistically greater in PPL than in PHL and HSL (p<0.05). The efficiency was not
      statistically different between the three groups (p=0.155). In conclusion, the
      efficiency of work production by paretic and spastic lower limb muscles was
      normal ( congruent with 20%) despite significant neurological impairments.

PMID- 16274916
TI  - Sagittal spine and lower limb movement during sit-to-stand in healthy young
      subjects.
AB  - This study aimed to determine the sagittal movement relationships between
      thoracic, lumbar spine and hip joints during sit-to-stand (STS). Forty-seven
      healthy young adults were videotaped performing STS at their preferred speed from
      a chair set at 100% knee height. Forward trunk lean prior to buttock lift-off
      (LO) was accomplished by concurrent lumbar and hip flexion (1:3). As the lumbar
      spine flexed the thoracic spine extended, resulting in a LO trunk angle of 45.7
      degrees (+/-5.8 degrees ) with respect to a horizontal reference. Following LO,
      the hip(s) and lumbar spine extended and the thoracic spine flexed, with the
      standing thoracic angle approximating the initial thoracic posture in sitting.

PMID- 16274917
TI  - Repeatability of surface EMG during gait in children.
AB  - Although mean amplitude and ON-OFF timing of muscle recruitment and
      electromyography (EMG) activation during gait is achieved by an age of six to
      eight years in normally developing children, recruitment dynamics illustrated by
      the shape of the EMG waveform may require continued developmental practice to
      achieve a stable pattern. Previous analyses have quantified the repeatability of
      the EMG waveform in adult subjects, but EMG variability for a pediatric
      population may be significantly different. The goal of this study was to quantify
      intra-session and inter-session variability in the phasic EMG waveform patterns
      from the lower limb muscles during self-selected speeds of walking in healthy
      normal children for comparison with adult variability in gait EMG. The variance
      ratio quantifies the repeatability of the integrated EMG waveform shape in a
      group of normally-developing children. Results reveal that between-session EMG
      waveform variability were similar in adult and pediatric populations, but within
      session variability for the children was approximately twice the published value
      for adults. Clinical implications of this pediatric EMG variability suggest
      cautious interpretation of data from limited trial samples or inter-session
      changes in performance of gait data.

PMID- 16274918
TI  - The Multiple Tasks Test as a predictor of falls in older adults.
AB  - PURPOSE: Falls are among the most common and serious problems facing the elderly.
      The Berg Balance Scale (BBS) is the gold standard in measuring falls risk. With
      higher functioning elders, a ceiling effect is often evidenced using the BBS. The
      purpose of this study was to determine if the Multiple Tasks Test (MTT) when used
      in high functioning community dwelling elderly correlated with the BBS. Secondly,
      this study assessed the unidimensionality of the MTT. If a relationship existed
      between the performance of multiple tasks and the potential loss of balance
      resulting in falls, then the MTT would be more appropriate than the BBS at
      predicting falls in higher functioning individuals. METHODS: Twenty-two
      independent community dwelling older adults were tested using both the MTT and
      the BBS on the same day at a senior center. DATA ANALYSIS: Correlations between
      the BBS and the MTT ranged between -0.765 and -0.79. The results of the Guttman's
      scalability analysis were a plus percentage ratio of 0.75 and an index of
      reproducibility of 0.93. Scales with these values are regarded as having evidence
      of unidimensionality. SUMMARY: All of the MTT tests correlated with the BBS. In
      addition, the MTT was found to be unidimensional. CONCLUSION: Although the MTT
      correlated with the BBS and was found to be a good cumulative measure, it would
      benefit from continued study to examine quantifiability, validity and
      reliability. With further refinement and study, the MTT may be useful at
      discriminating fallers from non-fallers in high functioning older adults.

PMID- 16274919
TI  - Increased muscular challenge in older adults during obstructed gait.
AB  - Skeletal muscle strength is known to decline with age. Although lower extremity
      (LE) muscle strength is critical to maintaining dynamic stability, few studies
      have investigated lower extremity muscle challenge during activities of daily
      living. The purpose of this study was to investigate the effects of age and
      obstructed gait on relative lower extremity muscular challenge, with respect to
      available joint strength. Fifteen healthy young and fifteen healthy older adults
      were asked to walk over level ground and step over obstacles. Pre-amplified
      surface electrodes were used to measure bilateral muscular activation of the
      gluteus medius (GM), vastus lateralis (VL), and gastrocnemius (GA). Muscle
      activation signals were normalized to peak magnitudes collected during maximal
      manual muscle testing (MMT). Normalized magnitudes were analyzed during the
      double-support phase for gluteus medius and vastus lateralis and during the
      single-support phase for gastrocnemius. A two-factor ANOVA was used to test for
      age group effect, with repeated measure of obstacle height. In general, older
      adults demonstrated greater relative activation levels compared to young adults.
      Gluteus medius activity was significantly greater in the elderly as compared to
      young during periods of double-support (weight transfer). Increased obstacle
      height resulted in greater relative activation in all muscles, confirming the
      increased challenge to the musculo-skeletal system. While healthy elderly adults
      were able to successfully negotiate obstacles of different heights during
      walking, their muscular strength capacity was significantly lower than young
      adults, resulting in relatively higher muscular demands. The resulting potential
      for muscular fatigue during locomotion may place individuals at higher risk for
      trips and/or falls.

PMID- 16274920
TI  - Gait termination: a review of experimental methods and the effects of ageing and
      gait pathologies.
AB  - The study of human gait has expanded and diversified to the extent that it is now
      possible to identify a substantive literature concerning a variety of gait tasks,
      such as gait initiation [Halliday SE, Winter DA, Frank JS, Patla AE, Prince F.
      The initiation of gait in young, elderly, and Parkinson's disease subjects. Gait
      Posture 1998;8:8-14; Mickelborough J, van der Linden ML, Tallis RC, Ennos AR.
      Muscle activity during gait initiation in normal elderly people. Gait Posture
      2004;19:50-57], stepping over and across obstacles [Patla AE, Prentice SD,
      Robinson C, Newfold J. Visual control of locomotion: strategies for changing
      direction and for going over obstacles. J Exp Psych 1991;17:603-34; Chen, HC,
      Ashton-Miller JA, Alexander NB, Schultz AB. Effect of age and available response
      time on ability to step over an obstacle. J Gerontol 1994;49:227-33; Sparrow WA,
      Shinkfield AJ, Chow S, Begg RK. Gait characteristics in stepping over obstacles.
      Hum Mov Sci 1996;15:605-22; Begg RK, Sparrow WA, Lythgo ND. Time-domain analysis
      of foot-ground reaction forces in negotiating obstacles. Gait Posture 1998;7:99
      109; Patla AE, Rietdyk S. Visual control of limb trajectory over obstacles during
      locomotion: effect of obstacle height and width. Gait Posture 1993;1:45-60]
      negotiating raised surfaces such as curbs and stairs [Begg RK, Sparrow WA. Gait
      characteristics of young and older individuals negotiating a raised surface:
      implications for the prevention of falls. J Gerontol Med Sci 2000;55A:147-54;
      Mcfayden BJ, Winter DA. An integrated biomechanical analysis of normal stair
      ascent and descent. J Biomech 1988;21:733-44]. In addition, increasing research
      interest in age-related declines in gait that might predispose individuals to
      falls has engendered a very extensive literature concerning ageing effects on
      gait. While rapid locomotor adjustments are common in the course of daily
      activities there has been no previous review of the findings concerning gait
      adaptations when walking is terminated both rapidly and unexpectedly. The aims of
      this review were first, to summarise the key research findings and methodological
      considerations from studies of termination. The second aim was to demonstrate the
      effects of ageing and gait pathologies on termination with respect to the
      regulation of step characteristics, lower-limb muscle activation patterns and
      foot-ground reaction forces.

PMID- 16274921
TI  - Assessment of sub-division of plantar pressure measurement in children.
AB  - Methods for the measurement of plantar pressure are poorly defined particularly
      when describing sub-sections of the plantar surface of the foot in the presence
      of deformity. The aim of this study was to assess foot pressure measurement in
      healthy children, using an automatic technique of sub-area definition that has
      the potential for objective evaluation of treatment of foot deformity. Twelve
      healthy children were examined on three occasions. Plantar pressure data were
      collected and time synchronised with force plate and stereophotogrammetric data.
      The footprint was divided into five sub-sections by using the position of the
      markers on the foot at mid-stance projected onto the pressure footprint.
      Repeatability for peak pressure and peak force was assessed. Automatic sub-area
      definition based on marker placement was found to be reliable in healthy
      children. A comparison of results revealed that peak vertical force was a more
      consistent measure than peak pressure for each of the five sub-areas. This
      suggests that force may be a more appropriate measurement for outcome studies.

PMID- 16274922
TI  - We have read with interest the article by Romei et al. published recently in Gait
      & Posture that advocates the use of the Normalcy Index proposed by Shutte et al.

PMID- 16274924
TI  - Arguments raised by the recent discovery that insulin and leptin are expressed in
      and secreted by human ejaculated spermatozoa.
AB  - The recent findings demonstrating that insulin and leptin are expressed in and
      secreted by human ejaculated spermatozoa raise the controversial issue related to
      mRNA function in male gamete. Capacitated sperm display an increased metabolism
      and overall energy expenditure presumably to affect the changes in sperm
      signaling and function during capacitation. However the relationship between the
      signaling events associated with capacitation and the change in sperm metabolism
      energy is poorly understood. It emerges from the findings here reported that both
      leptin and insulin may be crucial in ejaculated spermatozoa to manage their
      energy status. Immunoistochemical analysis revealed that in uncapacitated sperm
      insulin was located at the subacrosomial level, in the midpiece and through the
      tail while leptin was immunodetected at the equatorial segment and at the
      midpiece. Capacitated sperm display an overall decrease and a more uniform
      distribution in the signal for both hormones and this is in agreement with their
      enhanced release in the medium. Both hormones in ejaculated sperm somehow
      recapitulate the cross-talk between their signalling transductional pathways in
      somatic cells, resulting in the increase of phosphoinositide 3-kinase (PI3K)
      activity, AKT S473 and Glycogen synthase kinase 3 (GSK-3)-S9 phosphorylations.
      During capacitation GSK-3 phosphorylation was abolished suggesting how in
      capacitating sperm there is a block in glycogen synthesis. This reasonably
      indicates how during capacitation glycogen reserve is mobilized and this makes
      the glucose as energy substrate available. For instance insulin dismissed by
      ejaculated spermatozoa up-regulates Glucose 6-Phosphate Dehydrogenase (G6PDH),
      the rate-limiting enzyme in the pentose phosphate pathway (PPP), which has be
      shown to be crucial in the acquisition of fertilizing capability as well as to
      mediate gamete fusion. Insulin immunoneutralization or blockage of its release,
      dramatically down regulated G6PDH. Interestingly, in the presence of a disruptor
      of insulin signaling wortmannin, an inhibitor of PI3K, the intrinsic activity of
      G6PDH drops. Leptin appears to play similar action to that of insulin on G6PDH in
      sperm (data in progress). The enhanced activity of this enzyme induced by both
      hormones produces an increase of NADPH that is essential for fatty acid synthesis
      from acetyl CoA. These fatty acids have two possible fates: beta-oxidation to
      produce ATP or reesterification back into triacylglycerol. Inter-relationships of
      the classes of substrates of free fatty acids (FFA) and glucose utilized for
      energy, has been long established [Randle, P.J., 1964. The interrelationships of
      hormones, fatty acid and glucose in the provision of energy. Postgrad. Med. J.
      40, 457-463]. The authors observed in ejaculated spermatozoa what it occurs in
      somatic cells: FFA beta-oxidation tested utilizing the octanoil-CoA as substrate,
      appears to be stimulated by leptin and down-regulated by the contemporaneous
      presence of insulin in uncapacitated sperms. FFA beta-oxidation activity
      dramatically increases when capacitation starts, so it may be assumed the
      possibility that leptin may work to stimulate such enzymatic activity providing
      additional metabolic fuel to triggering capacitation process. The autonomous
      capability of sperm to release insulin and leptin suggests that they through an
      autocrine short loop may provide the recruitment of energy substrate according to
      sperm metabolic needs. This occurs independently by the systemic regulation and
      may represent a protective mechanism which preserves sperm fertilizing capability
      by any detrimental effects produced by long calorie restriction or by alterations
      occurring in the energy homeostasis at systemic level.

PMID- 16274925
TI  - Tissue-specific modulation of cyclooxygenase-2 (Cox-2) expression in the uterus
      and the v. cava by estrogens and phytoestrogens.
AB  - Cyclooxygenase 2 (Cox-2), an enzyme involved in prostaglandin production, is a
      key player in the development of pathologic changes, such as colorectal cancer,
      arteriosclerosis and thrombosis. In this study, we investigated the effects of
      estrogens, selective estrogen receptor modulators (SERMs), pure antiestrogens and
      phytoestrogens on the tissue-specific expression of Cox-2 in the uterus and the
      v. cava of ovariectomized female rats. Cox-2 expression could be detected in the
      uterine epithelium and in the endothelium of the v. cava. Cox-2 expression was
      time-dependently stimulated after administration of 17beta estradiol (E2) in the
      uterus. In the v. cava, E2 treatment resulted in a stimulated expression of the
      progesterone receptor (PR), a gene known to be regulated by E2, whereas Cox-2 was
      simultaneously down-regulated. Administration of the pure antiestrogen faslodex
      (Fas) had no effect on Cox-2 expression. In contrast, administration of tamoxifen
      (Tam) resulted in a decrease of Cox-2 expression in the v. cava but does not
      stimulate Cox-2 expression in the uterus. Interestingly, the same expression
      pattern of Cox-2 could be detected after dose-dependent administration of
      genistein (Gen). Here, down-regulation of Cox-2 could already be detected after
      administration of merely 0.5 mg/(kgBW) Gen, a dose where no effects on uterine
      weight were observed. In summary, our results demonstrate a reverse tissue
      specific regulation of Cox-2 expression by estrogens in the v. cava and uterus
      indicating the existence of complex molecular mechanisms which have to be
      characterized in future studies. Remarkably, Tam and the phytoestrogen Gen, both
      share the ability to decrease the expression of Cox-2 in the v. cava without
      effecting its uterine expression. These observations may be of great importance
      with respect to potential beneficial or adverse effects of estrogens, SERMs and
      phytoestrogens on the cardiovascular tissue.

PMID- 16274926
TI  - Quercetin arrests G2/M phase and induces caspase-dependent cell death in U937
      cells.
AB  - Quercetin, a natural product derived from grapes, has been shown to prevent
      carcinogenesis in murine models. We report here that quercetin induces anti
      proliferation and arrests G2/M phase in U937 cells. The G2/M phase accumulation
      was accompanied by an increase in the level of the cyclin B. In contrast, the
      level of the cyclin D, cyclin E, E2F1, and E2F2 was marked decreased in quercetin
      treated U937 cells. Removal of quercetin from the culture medium stimulates U937
      cells to synchronously re-enter the cell cycle, decrease expression level of
      cyclin B, and increased the expression level of cyclin D and cyclin E. These data
      demonstrate that quercetin causes reversible G2/M phase arrest, which was related
      with dramatic changes in the level of cyclin B, cyclin D, and cyclin E. Quercetin
      induced down-regulation of cyclin D and cyclin E was associated with suppression
      of transcriptional levels but not protein stability. In addition, quercetin
      treated U937 cells showed DNA fragmentation, increased sub-G1 population, and
      generated a 60kDa cleavage product of PLC-gamma1 in a dose-dependent manner,
      which were significantly inhibited by z-VAD-fmk. These data clearly indicate that
      quercetin-induced apoptosis is associated with caspase activation. In summary,
      the growth inhibition of the quercetin is highly related to cell cycle arrest at
      the G2/M phase and induction of caspase-dependent apoptosis in human promonocytic
      U937 cells.

PMID- 16274927
TI  - Tumor necrosis factor alpha inhibits aclacinomycin A-induced erythroid
      differentiation of K562 cells via GATA-1.
AB  - Up-regulation of tumor necrosis factor alpha (TNFalpha) is linked to solid tumors
      as well as to hematologic disorders including different forms of anemia and
      multiple myeloma. This cytokine was shown to contribute to inhibition of
      erythroid maturation mechanisms which are characterized by the expression of
      specific genes regulated by GATA-1 and NF-E2 transcription factors. Here, we
      assessed the inhibiting effect of TNFalpha on erythroid differentiation using
      K562 cells which can be chemically induced to differentiate towards the erythroid
      pathway by aclacinomycin A, an anthracyclin. Results show that induced
      hemoglobinization of K562 cells as well as gamma-globin and erythropoietin
      receptor gene expression are decreased by TNFalpha via the inhibition of GATA-1
      at its mRNA and protein expression level. Additionally, both constitutive and
      induced binding activity of GATA-1 is abolished and induced activation of a GATA
      1 driven luciferase reporter construct is inhibited. Altogether, our results
      provide insight into the molecular mechanisms of inflammation-induced inhibition
      of erythroid differentiation.

PMID- 16274928
TI  - Tyrosine transport in fibroblasts from healthy volunteers and patients with
      schizophrenia.
AB  - Aberrant tyrosine transport across the fibroblast membrane, as measured by lower
      Vmax and/or lower Km is a repeated finding in patients with schizophrenia. The
      aim of this study was to investigate the importance of two major transporters,
      the L- and A-systems and tyrosine transport in fibroblast cell lines from
      patients with schizophrenia and healthy volunteers. Fibroblast cell lines, n=6
      from healthy volunteers and n=6 from patients with schizophrenia, were included
      in the study. Uptake of [14-C] L-tyrosine in fibroblasts was measured using the
      cluster tray method in absence and presence of inhibitors. The uptake of tyrosine
      by the L-system was evaluated with the inhibitor 2-aminobicyclo heptane-2
      carboxylic acid (BCH) and the A-system with the inhibitor nonmetabolized methyl
      aminoisobutyric acid (MeAIB). Using [14-C] MeAIB the functionality of system A
      isoform 2, ATA2, was tested. BCH inhibited the uptake of tyrosine with 90%,
      showing that tyrosine transport in fibroblasts is mainly transported by the L
      system. Not more than 10% could be contributed by the A-system. Excess of MeAIB
      did not influence tyrosine kinetics. Moreover, MeAIB kinetics did not differ
      between the patients and the controls. In conclusion, aberrant tyrosine transport
      observed in patients with schizophrenia is probably linked to the one of the L
      systems and does not seem to involve the ATA2 transporter.

PMID- 16274929
TI  - Modeling thermal burns due to airbag deployment.
AB  - Automotive airbags are now a widely accepted safety measure designed to reduce
      morbidity associated with motor vehicle accidents. Their usage is increasing with
      multiple airbags (driver, passenger and side curtain) being fitted to many
      vehicles. However the deployment of airbags has been identified as causing
      injuries in some instances including minor burns. There are three mechanisms for
      thermal burns due to an airbag; contact with the hot expelled gases from the
      airbag, contact with the hot airbag itself and melting of clothing from either of
      these contacts. A mathematical model is used here to predict the likelihood and
      severity of the first two types of burns. It is shown that direct contact with
      high temperature exhaust gases venting from the airbag can indeed lead to burns
      and that burns from contacting the hot airbag material are possible but far less
      likely to occur.

PMID- 16274930
TI  - The application of new biosynthetic artificial skin for long-term temporary wound
      coverage.
AB  - Temporary dressings protect wounds from desiccation and infection. In our
      previous study, we used meshed acellular porcine dermis (APD) to enhance wound
      healing and decrease wound contraction; however, the wounds showed meshed scar.
      In this study, we produced an artificial skin composed of a cross-linked silicon
      sheet on the surface of APD which we have called silicone acellular porcine
      dermis (SAPD). This new artificial skin can protect the wound long enough to
      promote wound healing either by second intention or covered long enough until
      cultured epithelium autograft (CEA) or autologous skin graft can be harvested for
      permanent coverage. We delivered 4 cm x 5 cm full-thickness wound on the back of
      350 g Sprague-Dawley rats. Thirty-six rats were divided into two groups. Eighteen
      rats had SAPD and the other 18 were covered with Biobrane. The wounds were first
      examined 2 weeks after grafting and followed weekly for an additional 4 weeks to
      evaluate the wound and study pathological changes by using H.E. and Masson's
      stains. Wound size was calculated by ruler and analyzed by Student's t-test. At
      the 2-week inspection, both SAPD and Biobrane showed tight adherence to the wound
      with no change of wound size. Both the SAPD and Biobrane dermal templates were
      pink. In the Biobrane-covered group, the wounds contracted soon after the tie
      over dressing was removed. Its dermal layer is a layer of thin porcine dermal
      substance, which was promptly digested by tissue hyaluronidase and provides no
      real dermal template. In the SAPD-covered group however, the wound size was
      maintained significantly from third to sixth week after grafting (p<0.001). SAPD
      was designed with thick epidermal silicone and a well-organized porcine dermis so
      that it incorporates into the recipient wound. Clinically the silicone layer of
      SAPD dislodged from APD about 6-7 weeks after grafting and was followed by dermal
      matrix exposure and infection. In pathological examination, much like a human
      skin graft, new vessels were found in APD about 1 week after grafting with
      minimal inflammatory cells infiltrated in the graft and wound. Six weeks after
      grafting, the collagen of APD incorporated into the wound, showing palisade
      arrangement and no sign of rejection. In the Biobrane group however, the wounds
      showed severe inflammation, the porcine dermal matrix was digested and
      disappeared 3 weeks after coverage. In conclusion, SAPD is a thick biosynthetic
      artificial skin, which protects the rat wound significantly longer than Biobrane
      and prevents contraction. We expect that using of SAPD for temporary wound
      coverage will provide enough time to grow autologous-cultured epithelium or to
      reharvest skin grafts.

PMID- 16274931
TI  - Lactate: early predictor of morbidity and mortality in patients with severe
      burns.
AB  - A severe burn results in a devastating and unique derangement called burn shock.
      Historically, resuscitation has been guided by a combination of basic laboratory
      values, invasive monitoring and clinical findings, but the optimal guide to the
      endpoint of resuscitation remains controversial. One-hundred sixty-six patients,
      who were admitted to our Burn Unit, were enrolled in this prospective study.
      Resuscitation of these patients was undertaken according to the current standard
      of care. Parkland formula was used as a first approximation of acquired fluid
      administration rates and fluid administration was adapted in order to meet
      clinical needs. The aim of this study was to evaluate if plasma lactate is a
      useful parameter to estimate the severity of a burn shock. One of the main
      objectives was to evaluate, if the lactate clearance adds additional information.
      The results of this study indicate that the initial lactate level (Day 0) is a
      useful parameter to separate survivors from non-survivors. Moreover, a
      significant marker of shock and resuscitation was observed in evaluating the
      lactate clearance on Day 1. A better chance of survival occurs when resuscitation
      results in a lactate clearance to normal values within 24h (survival was 68% if
      the lactate reached normal values, compared to 32% if the lactate level remained
      supra-normal). In summary, we believe that measuring lactate and lactate
      clearance may help to detect critically injured patients either for adequacy of
      treatment, or selection of other therapeutic options.

PMID- 16274932
TI  - New technologies for burn wound closure and healing--review of the literature.
AB  - Methods for handling burn wounds have changed in recent decades. Increasingly,
      aggressive surgical approach with early tangential excision and wound closure is
      being applied leading to improvement in mortality rates of burn victims.
      Autografts from uninjured skin remain the mainstay of treatment. Autologous skin
      graft, however, has limited availability and is associated with additional
      morbidity and scarring. Severe burn patients invariably lack sufficient adequate
      skin donor sites requiring alternative methods of skin replacement. The present
      review summarizes available replacement technologies.

PMID- 16274933
TI  - Childhood trauma and diurnal cortisol disruption in fibromyalgia syndrome.
AB  - Adults with fibromyalgia syndrome report high rates of childhood trauma.
      Neuroendocrine abnormalities have also been noted in this population. Exploratory
      analyses tested relationships between retrospective reports of childhood trauma
      and diurnal salivary cortisol patterns among 85 women with fibromyalgia. Subjects
      with fibromyalgia completed self-reports of childhood physical, sexual and
      emotional abuse, as well as emotional and physical neglect. Recent major life
      events, current perceptions of stress, and depressive symptoms were also
      assessed. Salivary cortisol was collected six times per day for two consecutive
      days to assess diurnal rhythm, awakening response and mean cortisol levels.
      Hierarchical regression analyses were performed, controlling for age, relevant
      medications, life events, perceived stress, and depressive symptoms. Childhood
      physical abuse predicted flattened diurnal cortisol rhythms as well as greater
      cortisol responses to awakening. Sexual abuse was a second predictor of increased
      awakening cortisol responses. Patients with a history of trauma had markedly low
      levels of cortisol at the time of first awakening, partly explaining the results.
      These findings suggest that severe traumatic experiences in childhood may be a
      factor of adult neuroendocrine dysregulation among fibromyalgia sufferers. Trauma
      history should be evaluated and psychosocial intervention may be indicated as a
      component of treatment for fibromyalgia.

PMID- 16274934
TI  - Endocrine and behavioural plasticity in response to juvenile stress in the semi
      precocial rodent Octodon degus.
AB  - The present study in the South American rodent Octodon degus shows for the first
      time that the postnatal development of hypothalamic-pituitary-adrenal axis
      function in this semi-precocial species differs from that of altricial rodents,
      i.e. rats or mice, in several aspects. Our experiments revealed a particular
      pattern of hypothalamic-pituitary-adrenal axis activity during the first 3 weeks
      of life characterized by (i) a period of low plasma glucocorticoid
      concentrations, during which (ii) brief stress exposure (1 h parental separation)
      is able to elevate glucocorticoids significantly. In addition, (iii) repeated
      stress exposure (1 h parental separation daily) during the first 3 weeks of life
      resulted in females, but not in males, in an attenuated separation-induced
      increase of glucocorticoids, and a higher behavioural activity in both sexes at
      postnatal day 21. These data indicate that parental separation early in life acts
      as a 'strong' stressor in this species, which on the long run can alter endocrine
      stress response at the time of weaning in a sex-specific manner. These findings
      support the role of the hypothalamic-pituitary-adrenal axis as one of the key
      factors mediating the effects of early life stress on the neuronal network and
      behaviour in O. degus.

PMID- 16274935
TI  - Long-term follow-up of patients of intrahepatic malignancies treated with iodine
      125 brachytherapy.
AB  - PURPOSE: We investigated the role of intraoperative iodine-125 (125I)
      brachytherapy as a treatment option for unresectable primary and metastatic liver
      tumors. METHODS AND MATERIALS: Between 1989 and 2002, 64 patients with
      unresectable or residual disease after surgical resection for intrahepatic
      malignancies underwent 160-Gy permanent 125I brachytherapy. RESULTS: The median
      length of follow-up was 13.2 years. The overall 1-year, 3-year, and 5-year
      actuarial intrahepatic local control rates were 44%, 22%, and 22%, respectively,
      with a median time to liver recurrence of 9 months (95% CI, 6-12 months). The 5
      year actuarial intrahepatic control was higher for patients with solitary
      metastasis (38%) than for those with multiple metastases (6%, p = 0.04). The 1
      year, 3-year, and 5-year actuarial overall survival rates were 73%, 23%, and 5%,
      respectively (median, 20 months; 95% CI, 16-24; longest survival, 7.5 years).
      Overall survival was higher for patients with smaller-volume implants (p = 0.003)
      and for patients without prior liver resection (p = 0.002). No mortality
      occurred. Radiation-related complications were minimal. CONCLUSIONS: For select
      patients with unresectable primary and metastatic liver tumors for whom curative
      surgical resection is not an option, 125I brachytherapy is a safe and effective
      alternative to other locally ablative techniques and can provide long-term local
      control and increased survival.

PMID- 16274936
TI  - STI571 (Gleevec) improves tumor growth delay and survival in irradiated mouse
      models of glioblastoma.
AB  - PURPOSE: Glioblastoma multiforme (GBM) is a devastating brain neoplasm that is
      essentially incurable. Although radiation therapy prolongs survival, GBMs
      progress within areas of irradiation. Recent studies in invertebrates have shown
      that STI571 (Gleevec; Novartis, East Hanover, NJ) enhances the cytotoxicity of
      ionizing radiation. In the present study, the effectiveness of STI571 in
      combination with radiation was studied in mouse models of GBM. METHODS AND
      MATERIALS: Murine GL261 and human D54 GBM cell lines formed tumors in brains and
      hind limbs of C57BL6 and nude mice, respectively. GL261 and D54 cells were
      treated with 5 micromol/L of STI571 for 1 h and/or irradiated with 3 Gy. Protein
      was analyzed by Western immunoblots probed with antibodies to caspase 3, cleaved
      caspase 3, phospho-Akt, Akt, and platelet-derived growth factor receptor (PDGFR)
      alpha and beta. Tumor volumes were assessed in mice bearing GL261 or D54 tumors
      treated with 21 Gy administered in seven fractionated doses. Histologic sections
      from STI571-treated mice were stained with phospho-Akt and phospho-PDGFR beta
      antibodies. Kaplan-Meier survival curves were used to study the response of mice
      bearing intracranial implants of GL261. RESULTS: STI571 penetrated the blood
      brain barrier, which resulted in a reduction in phospho-PDGFR in GBM. STI571
      induced apoptosis in GBM was significantly enhanced by irradiation. STI571
      combined with irradiation induced caspase 3 cleavage in GBM cells. Glioblastoma
      multiforme response to therapy correlated with an increase in tumor growth delay
      and survival when STI571 was administered in conjunction with daily irradiation.
      CONCLUSION: These findings suggest that STI571 has the potential to augment
      radiotherapy and thereby improve median survival.

PMID- 16274937
TI  - Complete solution of the Rescorla-Wagner model for relative validity.
AB  - In several papers, useful methods for deriving predictions of the Rescorla-Wagner
      (R-W) model were presented. This article supplements those previous efforts,
      which could not solve one important problem. Those cases are considered in which
      infinite solutions exist. In such cases, the resulting associative strength is
      determined by the initial associative strength. An important example is the
      experimental paradigm called relative validity. Surprisingly, an easy, pencil-and
      paper solution can be derived. Based on the results of this paper, along with
      earlier ones, predictions can be derived for fairly broad conditions.

PMID- 16274939
TI  - Proceedings of Neonatal Update 2005. November, London, United Kingdom.

PMID- 16274938
TI  - Identification of sigma(V)-dependent genes of Bacillus subtilis.
AB  - The chromosome of Bacillus subtilis codes for seven extracytoplasmic function
      sigma factors the activity of which is modulated normally by a cognate anti-sigma
      factor. While inducing factors and genes for four of them (sigma(M), sigma(W),
      sigma(X), and sigma(Y)) have been identified, those of the remaining three sigma
      factors including sigma(V) remain elusive. The objective of the present study was
      the unequivocal identification of its anti-sigma factor and of genes controlled
      by sigma(V). In many cases reported so far the gene coding for the anti-sigma
      factor is located immediately downstream of the gene coding for the sigma factor,
      and both form a bicistronic operon. We could show by two different experimental
      approaches that this is also the case for sigV and rsiV. Under conditions of
      overproduction of sigma(V), 13 genes could be identified being induced several
      fold by the DNA macroarray technique. Induction of three of them was confirmed by
      Northern blots, and the potential promoter of sigV was identified by primer
      extension. This led to the deduction of a consensus sequence recognized by
      sigma(V).

PMID- 16274940
TI  - Withholding treatment, withdrawing treatment, and palliative care in the neonatal
      intensive care unit.
AB  - Advances in pharmacology and technology have sharply reduced mortality of
      extremely preterm infants at the expense of an increasing number of survivors
      with handicaps and disabilities. The EURONIC study among neonatal intensive care
      units across Europe demonstrates that treatment of infants born at the limits of
      viability raises challenging ethical, moral, legal, and emotional dilemmas among
      neonatologists, nurses, and parents alike. When is it wise to withhold or
      withdraw intensive care and, if so, what are the needs of the nonviable or dying
      infant, family, and neonatal staff to provide a humane and compassionate death?
      This process begins with a thorough determination of diagnosis and prognosis,
      followed by decision making on the basis of futility of treatment or quality-of
      life issues, and counseling of parents. Withholding or withdrawing of intensive
      care should be synonymous with palliative care. Perinatal audit and after-care of
      the family complete the process. The Dutch viewpoint and practice guidelines on
      withholding and withdrawing of neonatal intensive care are presented.

PMID- 16274941
TI  - Acute liver failure in neonates.
AB  - Acute liver failure (ALF) in neonates is a rare but often fatal event. Though in
      adults and older children, a main symptom of ALF is hepatic encephalopathy, this
      is very difficult to diagnose and prove in infants. Causes of ALF in neonates
      encompass metabolic, infectious and haematological disorders, congenital
      vascular/heart abnormalities, and drugs. Infants with ALF should only be treated
      in specialised paediatric hepatology centres with facilities for liver
      transplantation, since for many liver transplant, with a long term survival of
      over 60%, is the only therapeutic option.

PMID- 16274942
TI  - Neurophysiological testing in the newborn and infant.

PMID- 16274943
TI  - The neurological examination of the newborn baby.
AB  - This paper provides an overview of the value of a structured neonatal
      neurological examination that may be performed in different settings, from
      routine examination to research settings. We will report how a structured
      neurological examination can help to identify infants with central and peripheral
      nervous system involvement. We also describe a short but structured proforma to
      be used for the routine examination of full-term infants. We will finally
      describe a quantitative assessment to be used in research settings.

PMID- 16274944
TI  - Influence of post-emulsification drying processes on the microencapsulation of
      human serum albumin.
AB  - In the present work, methods used to microencapsulate Human Serum Albumin (HSA)
      in a biodegradable polymer were compared for their effects on the physicochemical
      characteristics of HSA-loaded microparticles and on the release and integrity of
      encapsulated HSA. The polymer used was poly(D,L-lactide-co-glycolide) (75:25)
      (PLGA) (Boehringer Ingelheim, Resomer RG 752, MW 20,900). Microparticles were
      formulated by (i) w/o/w emulsification and freeze-drying (EFD) or (ii) w/o/w
      emulsification and spray-drying (ESD). Particle morphology and size were
      evaluated by scanning electron microscopy and by laser diffraction analysis.
      Loading, encapsulation efficiency and protein release were determined using a
      commercial protein assay kit. Protein integrity was evaluated by sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. Particles
      produced by emulsification/spray-drying exhibited greater diversity in shape than
      those produced by emulsification/freeze-drying. Additionally, protein loading
      values were significantly higher for particles produced by emulsification/spray
      drying rather than particles produced by emulsification/freeze-drying. The
      structural integrity of encapsulated protein was confirmed for particles produced
      by both processes. The fraction of HSA released was similar for both
      formulations. The emulsification/spray-drying technique described appears to be a
      rapid and efficient method for the preparation of PLGA microparticles loaded with
      a model protein.

PMID- 16274945
TI  - Enhancement of brain distribution of anticancer agents using DeltaG, the 12 kDa
      active fragment of ZOT.
AB  - OBJECTIVE: The objective of this study was to evaluate the ability of DeltaG, the
      12 kDa active fragment of ZOT, to increase the brain distribution of MTX and
      paclitaxel, two commonly used anticancer agents with poor distribution into the
      brain. METHODS: As part of dose estimation of DeltaG, [14C]-sucrose (40
      microCi/kg), a hydrophilic paracellular marker, was co-administered with DeltaG
      (0, 400 and 800 microg/kg) with and without protease inhibitors to male Sprague
      Dawley rats (n=3 per group) via an intracarotid cannula. MTX (50 mg/kg) and [3H]
      paclitaxel (120 microCi/kg) were co-administered with the effective doses of
      DeltaG determined from the above study via the intracarotid cannula. Animals were
      euthanized by carbon dioxide asphyxiation at the specified time periods and brain
      and plasma samples were analyzed for the respective drug. RESULTS: The brain
      distribution of [14C]-sucrose was significantly enhanced at both doses of DeltaG.
      A fold enhancement in the B/P ratios of 1.88 and 2.68 was observed at the 400 and
      800 microg/kg doses respectively, when the protein was protected from metabolic
      degradation with PIs. DeltaG significantly increased the brain distribution of
      MTX at each of the doses administered, with over a seven-fold increase at the 600
      microg/kg dose. [3H]-paclitaxel brain AUC(0-60 min) was significantly higher in
      the presence of DeltaG (800 microg/kg with PIs) with a 2.5-fold enhancement in
      brain exposure. CONCLUSIONS: DeltaG significantly enhances the brain distribution
      of MTX (hydrophilic) and paclitaxel (lipophilic) and has the potential to be
      further developed as adjunct therapy to increase delivery of poorly permeable
      chemotherapeutic and other CNS targeted compounds.

PMID- 16274946
TI  - Conformational study of ketoprofen by combined DFT calculations and Raman
      spectroscopy.
AB  - A conformational study of ketoprofen was carried out by both density functional
      theory (DFT) calculations and Raman spectroscopy. Nine different geometries were
      found to correspond to energy minimum conformations but only one of them was
      experimentally detected in the condensed phase spectra. Those rotations which
      interconvert the five most stable conformers were studied and the intramolecular
      interactions governing the corresponding conformational preferences were
      assessed. A thorough vibrational analysis was performed, leading to the
      assignment of both the solid and liquid spectra. Evidence for formation of
      intermolecular hydrogen bonds between carboxylic groups of adjacent ketoprofen
      molecules, leading to dimeric entities, was obtained.

PMID- 16274947
TI  - Micro-mechanical properties of drying material bridges of pharmaceutical
      excipients.
AB  - This work is part of a larger research effort to elucidate the properties and
      morphology of pharmaceutical granules produced by wet-granulation. In this work,
      we measure forces exerted by the drying interparticle bridges. The bridges were
      formed from aqueous solutions of common pharmaceutical excipients both non
      polymeric (lactose, mannitol) and polymeric (hydroxypropyl cellulose (HPC),
      hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (povidone) (PVP)). We
      also study the morphology, microstructure and crystalline structure of
      solidifying bridges. We find that the solidifying behavior and final properties
      of bridges differ dramatically, depending on the composition of the solution.
      Bridges containing only lactose or mannitol tend to expand upon solidification,
      pushing the ends of the bridge apart; in contrast, pure HPC, HPMC, or PVP bridges
      tend to contract. Bridges crystallized from solution of the pure non-polymeric
      excipients are polycrystalline, brittle, and have low strength; bridges from the
      polymeric excipients are amorphous, strong and tough. When the polymeric and non
      polymeric excipients are used together, behavior closer to either one or the
      other extreme takes place. This depends on the relative amount of polymer in the
      bridge. It was also found that the different polymers impart different behavior
      on the bridge. The observed differences in solidification behavior have important
      implications for granule formation, drying and ultimate bridge and granule
      properties; these are discussed at some length in the paper.

PMID- 16274948
TI  - Pharmacological studies of anti-diarrhoeal activity of Gentianopsis paludosa.
AB  - The pharmacological studies of anti-diarrhoeal activity of Gentianopsis paludosa
      were carried out. The 75% ethanol extract (100-400 mg/kg) of Gentianopsis
      paludosa inhibited castor oil-induced diarrhoea and also reduced gastrointestinal
      motility in the charcoal meal test in mice. In the rabbit-isolated ileum, the
      extract showed inhibitory effects not only on its spontaneous contraction, but
      also on acetylcholine (Ach, 0.1 mM)- and KCl (60 mM)-induced contractions.
      Furthermore, the ethanol extract (0.4-0.6 mg/ml) shifted the CaCl2 dose-effect
      curves to the right in a non-competitive manner and significantly reduced the
      acetylcholine-induced contraction of isolated ileum in Ca2+-free solution like
      verapamil (0.1 mM), which suggest that the extract interferes with Ca2+ movement.
      These results support the traditional use of Gentianopsis paludosa in the
      treatment of diarrhoea.

PMID- 16274949
TI  - [Nasopharyngeal carriage of Streptococcus pneumoniae in healthy children, 2 to 24
      months of age, in New-Caledonia].
AB  - OBJECTIVES: The aims of this study were to determine the prevalence of
      pneumococcal nasopharyngeal carriage in New-Caledonian children less than two
      years of age, to define risk factors for carriage, and to document the serotypes
      present in New Caledonia prior to the implementation of the conjugate
      pneumococcal vaccine. METHOD AND RESULTS: From August 2002 to April 2003,
      nasopharyngeal samples were collected on 1040 children less than two years of age
      during scheduled visits to dispensaries for routine immunization. Of the 1040
      samples, 544 (52%) were positive for Streptococcus pneumoniae. The percentage of
      pneumococcal strains with reduced susceptibility to penicillin (PRSP) was 21%.
      Several risk factors for pneumococcal carriage were identified. These included
      the Province that the child lived in, the ethnic group, age, and having a sibling
      less than 6 years of age. Risk factors for carriage of PRSP carriage were similar
      but also included additional risk factors such as attendance at day care and a
      history of antibiotic treatment. The eight most frequent serotypes were 6B, 19F,
      14, 23F, 6A, 19A, 11A, and 16F. These serotypes accounted for 60% of all strains
      detected. The most frequent serotypes of PRSP were 14, 9 V, 19F, 23F, and 6B.
      They were more often identified in european children and 80% were vaccine
      serotypes. However, overall 250/544 (46%) of all pneumococcal isolates were those
      included in the 7 serotype vaccine.

PMID- 16274950
TI  - [Cardiovascular events in the course of tetanus: a prospective study on 30 cases
      in the infectious diseases clinic, in the Fann teaching hospital, Dakar].
AB  - OBJECTIVES: This prospective study had for aim to determine the frequency and
      characteristics of cardiovascular events in the course of tetanus. PATIENTS AND
      METHODS: From September to December 2002, we studied all patients over 4 years of
      age presenting with tetanus without any documented underlying disease. RESULTS:
      Thirty cases were included (mean age 36+/-20 years; sex-ratio 2.3). Seventy-three
      per cent had a mild-gravity tetanus (stage II of Mollaret) upon admission. One
      hundred and seventeen ECG were recorded and 93.3% of the patients had more than
      one abnormality: arrhythmia (24 cases), prolonged QT interval (23 cases),
      ventricular hypertrophia (17 cases), and atrial hypertrophia (4 cases) especially
      left (3 cases), failure of AV conduction (3 cases), ST segment depression (3
      cases), left and right axis deviation (3 cases), baseline undulation (3 cases)
      and repolarization disturbances (1 case). All patients had a normal Doppler
      echocardiographic examination. The mean hospitalization stay was 11.6+/-1.4 days
      and complications were noted in 60%; sinus tachycardia in apyrexia (5 cases),
      instable BP (5 cases), excessive sweatiness in apyrexia (1 case), and access of
      bradycardia with sudden cardiac arrest (2 cases). 8 patients died (26.7%). Six
      patients with cardiac autonomic dysfunction died, the case fatality rate being
      statistically higher in this group (P=0.007). A prolonged QT interval, sinus
      tachycardia and left ventricular hypertrophia were statistically more frequent at
      the acute phase of the illness. CONCLUSION: The case fatality rate of tetanus is
      still high, due among others to autonomic dysfunctions.

PMID- 16274951
TI  - Ontogenetic profile of ectonucleotidase activities from brain synaptosomes of
      pilocarpine-treated rats.
AB  - Adenosine, a well-known neuromodulator, can act as an endogenous anticonvulsant
      via the activation of adenosine A1 receptors. This adenine nucleoside can be
      produced in the synaptic cleft by the ectonucleotidase cascade, which includes
      the nucleoside triphosphate diphosphohydrolase (NTPDase) family and ecto-5'
      nucleotidase. It has been previously reported that ectonucleotidase activities
      are increased in female adult rats submitted to the pilocarpine model of
      epilepsy. Several studies have suggested that the immature brain is less
      vulnerable to morphologic and physiologic alterations after status epilepticus
      (SE). Here, we evaluate the ectonucleotidase activities of synaptosomes from the
      hippocampus and cerebral cortex of male and female rats at different ages (7-9,
      14-16 and 27-30-day old) submitted to the pilocarpine model of epilepsy. Our
      results show that ATP and ADP hydrolysis in the hippocampus and cerebral cortex
      were not altered by the pilocarpine treatment in female and male rats at 7-9, 14
      16 and 27-30 days. There were no changes in AMP hydrolysis in female and male
      rats submitted to the model at different ages, but a significant increase in AMP
      hydrolysis (71%) was observed in synaptosomes from the cerebral cortex of male
      rats at 27-30 days. Pilocarpine-treated male rats (60-70-day old) presented an
      enhancement in ectonucleotidase activities in the synaptosomes of the cerebral
      cortex (33, 40 and 64% for ATP, ADP and AMP hydrolysis, respectively) and
      hippocampus (55, 98 and 101% for ATP, ADP and AMP hydrolysis, respectively).
      These findings highlight differences between the purinergic system of young and
      adult rats submitted to the pilocarpine model of epilepsy.

PMID- 16274952
TI  - Production and characterization of recombinant equine prorelaxin.
AB  - Relaxin is a peptide hormone produced by a wide variety of mammals. In the horse,
      the placenta is the major source of relaxin. Since pure equine relaxin is
      difficult to obtain to study its role in the pregnant mare, the objectives of
      this study were to produce recombinant equine prorelaxin and characterize its
      immunological and biological activity. First, an equine relaxin gene cassette was
      transfected into immortalized bovine mammary epithelial (MAC-T) cells. Second,
      immunological activity of media conditioned by transfected MAC-T cells was tested
      by Western blotting and quantified using a homologous equine radioimmunoassay.
      Finally, bioactivity of the conditioned media was tested using the human monocyte
      cell line, THP-1, which exhibits a rapid and dose-dependent increase in the
      accumulation of cAMP upon binding relaxin. The results showed that conditioned
      media, concentrated 5x, yielded 4.11 +/- 0.81 ng/ml recombinant equine
      prorelaxin. In addition, a 19 kDa immunoreactive band, corresponding to the
      expected size of equine prorelaxin, was visualized by SDS-PAGE. THP-1 cells
      incubated with conditioned media (5x) from transfected cells, in the presence of
      forskolin (1 microM) and isobutylmethylxanthine (50 microM), showed an increase
      in cAMP production over media from mock-transfected cells alone. In conclusion,
      recombinant equine prorelaxin secreted by MAC-T cells was both immunologically
      and biologically active. This study demonstrates the first attempt to produce
      recombinant equine prorelaxin, important for further study of the role of relaxin
      in the mare.

PMID- 16274953
TI  - Surgical management of endometrial cancer in Slovak Republic.
AB  - AIM: To evaluate the routine surgical treatment of endometrial cancer in Slovak
      Republic in relation to current international recommendations. METHODS: A
      retrospective study based on a questionnaire was undertaken. Data on surgical and
      post-operative adjuvant therapy of endometrial cancer patients in Slovakia in
      2001 were collected, assessed and validated for good clinical practice. RESULTS:
      We presented data of 298 cases of endometrial adenocarcinoma from 48 of 66 Slovak
      gynecologic departments. Laparotomy with hysterectomy and bilateral salpingo
      oophorectomy was performed in 280/298 patients. Peritoneal washings were examined
      in 41/298 cases. Lymphadenectomy (pelvic and/or para-aortic) was performed in
      52/298 of the women. Malignancy remained undiagnosed in 29/298 of the cases until
      it was detected by histological investigation of extirpated uterus. CONCLUSION:
      The study demonstrates that surgical management of endometrial cancer is far from
      optimal. It seems necessary to restrict treatment to the centres with gynecologic
      oncologists trained in pelvic surgery.

PMID- 16274954
TI  - Controversies between surgical and percutaneous radiofrequency ablation.

PMID- 16274955
TI  - Fluoroquinolone resistance in hematopoietic stem cell transplant recipients with
      infectious complications.
AB  - The infectious complications are an important cause of morbidity and mortality in
      hematopoietic stem cell transplant (HSCT) recipients. Our retrospective study has
      the objective to evaluate the incidence, clinical and bacteriologic features of
      documented infections in these patients. The frequency of infectious
      complications was analysed in 42 patients with hematologic malignancies who
      received HSCT from January to December 2002 at Pisa General Hospital. Thirty
      three patients underwent autologous HSCT and 9 received allogeneic HSCT. All
      patients received acyclovir, fluconazole and fluoroquinolones as prophylactic
      regimen. A total of 38 infectious episodes were recognized in 22 patients during
      the early post-HSCT period (N=27) and in the late post-HSCT period (N=11).
      Infectious complications rate correlated positively with the deepness and length
      of neutropenia in the early period. There were 21 episodes of sepsis (the
      majority by coagulase negative staphylococci), 2 pneumonias and 1 vertebral
      osteomyelitis. All staphylococcus strains were, in vitro, resistant to oxacillin
      and ciprofloxacin and 8 out of 15 gram negative rods were resistant to
      ciprofloxacin. Most of the infectious complications were cured with appropriated
      antimicrobial therapy and/or with engraftment and, in 4 cases, with central
      catheter removal. One patient developed a positive CMV antigenemia; a pre-core
      mutant form of HBV reactivation was diagnosed in another patient. No cases of
      invasive fungal infections were recognised. Five patients died but only one from
      infection (septic shock). Pneumonia was a coexisting cause of death in 2 patient
      in the late period. We can conclude that most of infectious complications, that
      occurred in the early period post-HSCT were due to coagulase negative
      staphylococci and gram negative rods resistant to ciprofloxacin. For this reason,
      the usefulness of fluoroquinolone prophylaxis in HSCT recipients should be
      reevaluated.

PMID- 16274956
TI  - Variations in the mRNA expression of inflammatory mediators, markers of
      differentiation and lipid-metabolizing enzymes caused by sodium lauryl sulphate
      in cultured human keratinocytes.
AB  - Detergents are well known irritants. Effects of the detergent sodium lauryl
      sulphate (SLS) on cell toxicity using the XTT assay and mRNA expression of
      inflammatory mediators, markers of keratinocyte differentiation and enzymes
      synthesizing barrier lipids using real-time PCR were studied in cultured
      differentiated keratinocytes. After exposure for 24 h to SLS concentrations at
      0.002% or above, toxic effects were observed. When a lower SLS concentration
      (0.00075%) was used the mRNA expression of inflammatory mediators peaked around 4
      8 h. The expression of enzymes involved in the synthesis of cholesterol, fatty
      acids and ceramides and markers of keratinocyte differentiation also increased
      but after 24 h. In cells exposed to 0.000125-0.0015% SLS, a concentration
      dependent induction of the expression of inflammatory mediators was found after 4
      h. Similar changes were found after 24 h for involucrin and enzymes involved in
      ceramide synthesis. The mRNA expression of HMG-CoA synthase and reductase, long
      chain acyl-CoA synthase and transglutaminase also peaked after 24 h, but maximal
      induction was observed already at 0.00075% SLS. In conclusion, SLS induces an
      inflammatory response in keratinocytes and alters the mRNA expression of
      important barrier lipid enzymes and markers of keratinocyte differentiation, of
      possible importance for the irritant properties of SLS.

PMID- 16274957
TI  - The effect of speaking context on elicitation of habitual pitch.
AB  - The purpose of this study was to investigate if there was an effect of speaking
      context on the elicitation of habitual pitch [speaking fundamental frequency
      (SFF)]. Six simulated speaking contexts were created (speaking during a voice
      evaluation, speaking in public, speaking to a peer, speaking to a superior,
      speaking to a subordinate, and speaking to a parent or spouse), and the SFF for
      30 adult women with normal voice was compared across these contexts. A one-way
      analysis of variance (ANOVA) revealed a statistically significant (P < 0.001)
      effect of simulated speaking context on SFF, with post hoc analyses indicating a
      statistically significant difference in SFF while "speaking to a superior" (P <
      0.001) and "speaking to a subordinate" (P < 0.001). Possible reasons for an
      effect of speaking context are discussed. Also, the implications of the use of
      varied speaking contexts when eliciting SFF are discussed, as is the possibility
      of an effect of speaking context on the elicitation of other clinically useful
      voice parameters.

PMID- 16274958
TI  - Recurrent dysphonia and acitretin.
AB  - We report the case of a woman complaining of dysphonia while she was treated by
      acitretin. Her symptoms totally regressed after drug withdrawal and reappeared
      when acitretin was reintroduced. To our knowledge, this is the first case of
      acitretin-induced dysphonia. This effect may be related to the pharmacological
      effect of this drug on mucous membranes.

PMID- 16274959
TI  - The relationship between chronic cough and paradoxical vocal fold movement: a
      review of the literature.
AB  - SUMMARY: Chronic cough (CC) and paradoxical vocal fold movement (PVFM) are
      debilitating conditions. PVFM has been given many labels, including vocal cord
      dysfunction, Munchausen's stridor, functional inspiratory stridor, nonorganic
      functional or psychogenic upper airway obstruction, factitious asthma,
      psychogenic stridor, emotional laryngeal wheezing, and episodic laryngeal
      dyskinesia. Although CC and PVFM have been considered separate entities in many
      reports, there is preliminary support for the notion that there may be an
      underlying link between these two conditions. Speech pathologists have become
      increasingly involved in the treatment of these patients and therefore need to
      understand the theoretical background of these disorders, the pathophysiological
      links between the two, and the impact of voice disorders on these populations.
      The aim of this article is to review the current literature on CC and PVFM from a
      speech pathology perspective to provide a model for defining and conceptualizing
      the disorders and to provide a framework for management and future research.

PMID- 16274960
TI  - Identification of a basolateral sorting signal within the cytoplasmic domain of
      the interleukin-6 signal transducer gp130.
AB  - Interleukin-6-type cytokine receptors are expressed in polarized cells such as
      hepatocytes and intestinal cells. For the interleukin-6-receptor gp80 and its
      signal transducer gp130, a preferential basolateral localization was demonstrated
      in Madin-Darby canine kidney (MDCK) cells and two basolateral sorting signals
      were identified within the cytoplasmic domain of gp80. The cytoplasmic tail of
      gp130 is responsible for signaling via the Janus kinase/signal transducer and
      activator of transcription pathway. In addition, it mediates the internalization
      of the receptor complex which is dependent on a di-leucine motif. Truncated gp130
      lacking the cytoplasmic domain is sorted apically in MDCK cells. For
      identification of the basolateral sorting signal(s) of gp130, a series of
      deletion mutants in the cytoplasmic domain of gp130 have been generated and
      stably expressed in MDCK cells. Biotinylation analyses of these mutants show that
      a ten amino acids sequence between amino acids 782 and 792 which contains the di
      leucine internalization motif is also essential for a basolateral sorting.
      Accordingly, we detect apical delivery of a gp130 mutant in which the di-leucine
      motif has been exchanged by two alanines (gp130LL/AA). These findings indicate
      that the di-leucine motif which directs the internalization of the IL-6 receptor
      complex also mediates the basolateral sorting of the signal transducer gp130.

PMID- 16274961
TI  - Detection of gyrA mutations associated with ciprofloxacin resistance in Neisseria
      gonorrhoeae by rapid and reliable pre-programmed short DNA sequencing.
AB  - Quinolone resistance is rapidly increasing in Neisseria gonorrhoeae and is posing
      a significant public health threat that requires constant surveillance. A rapid
      and reliable mutation detection assay has been developed. The assay is based on
      pre-programmed short DNA sequencing and is designed to detect point mutations in
      the gyrA gene that are highly related to ciprofloxacin resistance, i.e. in codons
      91 and 95. By developing an assay based on pyrosequencing and exploiting the pre
      programmed nucleotide dispensation capability of this technology, the sequence
      comprising the mutations will be analysed and promptly reveal whether the N.
      gonorrhoeae pathogen carries resistance to ciprofloxacin. A panel of 40 N.
      gonorrhoeae clinical isolates, of which 27 phenotypically displayed decreased
      susceptibility or resistance to ciprofloxacin, was used in the present study. All
      point mutations in the short stretch of the N. gonorrhoeae gyrA gene were easily
      discriminated, and the genotypic results obtained by pre-programmed sequencing
      were mainly in agreement with the phenotypically identified decreased
      susceptibility or resistance to ciprofloxacin. The new method used in the present
      study has the potential for rapid and reliable identification of known as well as
      previously unknown drug resistance mutations.

PMID- 16274962
TI  - Association study between the novel functional polymorphism of the serotonin
      transporter gene and suicidal behaviour in schizophrenia.
AB  - A serotonin transporter gene linked polymorphic region (5-HTTLPR) has been
      investigated in several genetic association studies, including studies of
      schizophrenia and suicidality. The current study was designed to examine whether
      the new long (A/G) variant polymorphism of the 5-HTT gene may be associated with
      suicide attempts of 290 Caucasian schizophrenic patients. Among these patients,
      92 had a history of suicide attempt. No association with history of suicide
      attempt was found in the multiallelic 5-HTTLPR (p = 0.305), however we found
      significant association with the intron 2 VNTR polymorphism (p = 0.018). When we
      performed a haplotype analysis, we found association between suicide attempt and
      haplotype distribution (p = 0.031). These findings suggest that the intron 2 VNTR
      polymorphism in serotonin transporter gene may influence suicidal behaviour in
      schizophrenia.

PMID- 16274963
TI  - The vHNF1 homeodomain protein establishes early rhombomere identity by direct
      regulation of Kreisler expression.
AB  - The early transcriptional hierarchy that subdivides the vertebrate hindbrain into
      seven to eight segments, the rhombomeres (r1-r8), is largely unknown. The
      Kreisler (MafB, Krml1, Val) gene is earliest gene expressed in an r5/r6
      restricted manner and is essential for r5 and r6 development. We have identified
      the S5 regulatory element that directs early Kreisler expression in the future
      r5/r6 domain in 0-10 somite stage embryos. variant Hepatocyte Nuclear Factor 1
      (vHNF1/HNF1beta/LF-3B) is transiently expressed in the r5/r6 domain of 0-10
      somite stage embryos and a vHNF1binding site within this element is essential but
      not sufficient for r5/r6-specific expression. Thus, early inductive events that
      initiate Kreisler expression are clearly distinct from later-acting ones that
      modulate its expression levels. This site and some of the surrounding sequences
      are evolutionarily conserved in the genomic DNA upstream of the Kreisler gene
      among species as divergent as mouse, humans, and chickens. This provides the
      first evidence of a direct requirement for vHNF1 in initiation of Kreisler
      expression, suggests that the role of vHNF1 is evolutionarily conserved, and
      indicates that vHNF1 collaborates with other transcription factors, which
      independently bind to the S5 regulatory region, to establish the r5/r6 domain.

PMID- 16274964
TI  - Fate of tetraploid cells in 4n<-->2n chimeric mouse blastocysts.
AB  - Previous studies have shown that tetraploid (4n) cells rarely contribute to the
      derivatives of the epiblast lineage of mid-gestation 4n<-->2n mouse chimeras. The
      aim of the present study was to determine when and how 4n cells were excluded
      from the epiblast lineage of such chimeras. The contributions of GFP-positive
      cells to different tissues of 4n<-->2n chimeric blastocysts labelled with tauGFP
      were analysed at E3.5 and E4.5 using confocal microscopy. More advanced E5.5 and
      E7.5 chimeric blastocysts were analysed after a period of diapause to allow
      further growth without implantation. Tetraploid cells were not initially excluded
      from the epiblast in 4n<-->2n chimeric blastocysts and they contributed to all
      four blastocyst tissues at all of the blastocyst stages examined. Four steps
      affected the allocation and fate of 4n cells in chimeras, resulting in their
      exclusion from the epiblast lineage by mid-gestation. (1) Fewer 4n cells were
      allocated to the inner cell mass than trophectoderm. (2) The blastocyst cavity
      tended to form among the 4n cells, causing more 4n cells to be allocated to the
      hypoblast and mural trophectoderm than the epiblast and polar trophectoderm,
      respectively. (3) 4n cells were depleted from the hypoblast and mural
      trophectoderm, where initially they were relatively enriched. (4) After
      implantation 4n cells must be lost preferentially from the epiblast lineage.
      Relevance of these results to the aetiology of human confined placental mosaicism
      and possible implications for the interpretation of mouse tetraploid
      complementation studies of the site of gene action are discussed.

PMID- 16274965
TI  - Development of functional thymic epithelial cells occurs independently of
      lymphostromal interactions.
AB  - The thymus provides a specialised microenvironment for the development of T-cell
      precursors. This developmental programme depends upon interactions with stromal
      cells such as thymic epithelial cells, which provide signals for proliferation,
      survival and differentiation. In turn, it has been proposed that development of
      thymic epithelial cells themselves is regulated by signals produced by developing
      thymocytes. Evidence in support of this symbiotic relationship, termed thymic
      crosstalk, comes from studies analysing the thymus of adult mice harbouring
      blocks at specific stages of thymocyte development, where it is difficult to
      separate mechanisms regulating the initial development of thymic epithelial cells
      from those regulating their maintenance. To distinguish between these processes,
      we have analysed the initial developmental programme of thymic epithelial cells
      within the embryonic thymus, in either the presence or absence of normal T-cell
      development. We show that keratin 5+8+ precursor epithelial cells present in the
      early thymic rudiment differentiate into discrete cortical and medullary
      epithelial subsets displaying normal gene expression profiles, and acquire
      functional competence, independently of signals from T-cell precursors. Thus, our
      findings redefine current models of thymus development and argue against a role
      for thymocyte-epithelial cell crosstalk in the development of thymic epithelial
      progenitors.

PMID- 16274966
TI  - Two families of candidate taste receptors in fishes.
AB  - Vertebrates receive tastants, such as sugars, amino acids, and nucleotides, via
      taste bud cells in epithelial tissues. In mammals, two families of G protein
      coupled receptors for tastants are expressed in taste bud cells-T1Rs for sweet
      tastants and umami tastants (l-amino acids) and T2Rs for bitter tastants. Here,
      we report two families of candidate taste receptors in fish species, fish T1Rs
      and T2Rs, which show significant identity to mammalian T1Rs and T2Rs,
      respectively. Fish T1Rs consist of three types: fish T1R1 and T1R3 that show the
      highest degrees of identity to mammalian T1R1 and T1R3, respectively, and fish
      T1R2 that shows almost equivalent identity to both mammalian T1R1 and T1R2.
      Unlike mammalian T1R2, fish T1R2 consists of two or three members in each
      species. We also identified two fish T2Rs that show low degrees of identity to
      mammalian T2Rs. In situ hybridization experiments revealed that fish T1R and T2R
      genes were expressed specifically in taste bud cells, but not in olfactory
      receptor cells. Fish T1R1 and T1R2 genes were expressed in different subsets of
      taste bud cells, and fish T1R3 gene was co-expressed with either fish T1R1 or
      T1R2 gene as in the case of mammals. There were also a significant number of
      cells expressing fish T1R2 genes only. Fish T2R genes were expressed in different
      cells from those expressing fish T1R genes. These results suggest that
      vertebrates commonly have two kinds of taste signaling pathways that are defined
      by the types of taste receptors expressed in taste receptor cells.

PMID- 16274968
TI  - Special issue honouring Professor Alexander Pines on his 60th birthday.

PMID- 16274967
TI  - Role of crescent in convergent extension movements by modulating Wnt signaling in
      early Xenopus embryogenesis.
AB  - The Xenopus gene crescent encodes a member of the secreted Frizzled-related
      protein (sFRP) family and is expressed in the head organizer region. However, the
      target and function of Crescent in early development are not well understood.
      Here, we describe a role of Crescent in the regulation of convergent extension
      movements (CEMs) during gastrulation and neurulation. We show that overexpression
      of Crescent in whole embryos or animal caps inhibits CEMs without affecting
      tissue specification. Consistent with this, Crescent efficiently forms complexes
      with Xwnt11 and Xwnt5a, in contrast to another sFRP, Frzb1. As expected, the
      inhibitory effect of Crescent or Xwnt11 on CEMs is cancelled when both proteins
      are coexpressed in the neuroectoderm. Interestingly, when coexpressed in the
      dorsal mesoderm, the activity of Xwnt11 is rather enhanced by Crescent.
      Supporting this finding, the inhibition of CEMs by Crescent in mesodermalized but
      not neuralized animal caps is reversed by the dominant-negative form of Cdc42, a
      putative mediator of Wnt/Ca2+ pathway. Antisense morpholino oligos for Crescent
      impair neural plate closure and elicit microcephalic embryos with a shortened
      trunk without affecting early tissue specification. These data suggest a
      potential role for Crescent in head formation by regulating a non-canonical Wnt
      pathway positively in the adjacent posterior mesoderm and negatively in the
      overlying anterior neuroectoderm.

PMID- 16274969
TI  - Spectral editing based on selective excitation and Lee-Goldburg cross
      polarization under magic angle spinning.
AB  - We show that a Gaussian-shaped pulse can be used to excite selected 1H signals in
      hydroxyapatite, monetite and H-Y zeolite loaded with trimethylphosphine oxide
      (TMPO). This selective excitation method can be incorporated into Lee-Goldburg
      (LG) cross-polarization to obtain useful spectral editing opportunity. This new
      strategy has been applied to identify the Bronsted and the Lewis acid sites in H
      Y zeolite using TMPO as the probe molecule.

PMID- 16274970
TI  - Effect of pulverization of the bulk powder on the hydration of creatine anhydrate
      tablets and their pharmaceutical properties.
AB  - The hydration behavior and expansion properties of untreated and pulverized
      creatine anhydrate (CRA) tablets were studied under 60 and 75%RH at 25 degrees C
      by using differential scanning calorimetry (DSC), and powder X-ray diffraction
      (PXRD). The tablet hardness of untreated and pulverized CRA tablets was
      significantly decreased after hydration. There was a linear relationship between
      the degree of hydration and the tablet hardness of untreated CRA tablets
      compressed at 1000 kg/cm2. In contrast, the relationship between the degree of
      hydration and the tablet hardness of pulverized CRA tablets was nonlinear. These
      results suggest that the reduction in hardness of pulverized CRA tablets does not
      depend solely on the hydration level of crystal water. PXRD analysis indicated
      that the diffraction pattern of the pulverized CRA powder was similar to that of
      the untreated CRA powder. However, the diffraction intensity of the pulverized
      CRA powder was slightly lower than that of the untreated CRA powder at high
      angle. The micropore radius of both untreated and pulverized CRA tablets was
      significantly increased after hydration, but analysis of the relationship between
      micropore radius and fractional hydration of crystal water showed that untreated
      CRA tablets were more affected than pulverized CRA tablets. Therefore, the
      reduction in tablet hardness depends not only on the hydration behavior but also
      on the crystal orientation of the CRA powder.

PMID- 16274971
TI  - Computational approaches to modeling drug transporters.
AB  - Computational modeling has advanced our understanding of drug absorption, tissue
      distribution, excretion and toxicity profiles by providing both direct and
      indirect knowledge of drug-transporter interactions that would otherwise be
      unavailable using experimental methods. Currently, two complementary approaches
      are available in modeling transporters: substrate-based and transporter-based
      methods. The transporter-based approach directly predicts the transporter's three
      dimensional structure to assist in understanding the drug transport process,
      whereas substrate-based models infer such information by studying a group of
      substrates or inhibitors with measured activities. In this review, the available
      strategies in both transporter-based and substrate-based approaches are explained
      and illustrated with applications and case studies. With increasing computational
      power and continuously improving modeling algorithms, computational techniques
      can assist in further understanding transporter-substrate interactions as well
      as, the optimization of transporter-directed drug design.

PMID- 16274972
TI  - Predicting spike times of a detailed conductance-based neuron model driven by
      stochastic spike arrival.
AB  - Reduced models of neuronal activity such as integrate-and-fire models allow a
      description of neuronal dynamics in simple, intuitive terms and are easy to
      simulate numerically. We present a method to fit an integrate-and-fire-type model
      of neuronal activity, namely a modified version of the spike response model, to a
      detailed Hodgkin-Huxley-type neuron model driven by stochastic spike arrival. In
      the Hogkin-Huxley model, spike arrival at the synapse is modeled by a change of
      synaptic conductance. For such conductance spike input, more than 70% of the
      postsynaptic action potentials can be predicted with the correct timing by the
      integrate-and-fire-type model. The modified spike response model is based upon a
      linearized theory of conductance-driven integrate-and-fire neurons.

PMID- 16274974
TI  - Local networks in visual cortex and their influence on neuronal responses and
      dynamics.
AB  - Networks of neurons in the cerebral cortex generate complex outputs that are not
      simply predicted by their inputs. These emergent responses underlie the function
      of the cortex. Understanding how cortical networks carry out such transformations
      requires a description of the responses of individual neurons and of their
      networks at multiple levels of analysis. We focus on orientation selectivity in
      primary visual cortex as a model system to understand cortical network
      computations. Recent experiments in our laboratory and others provide significant
      insight into how cortical networks generate and maintain orientation selectivity.
      We first review evidence for the diversity of orientation tuning characteristics
      in visual cortex. We then describe experiments that combine optical imaging of
      orientation maps with intracellular and extracellular recordings from individual
      neurons at known locations in the orientation map. The data indicate that
      excitatory and inhibitory synaptic inputs are summed across the cortex in a
      manner that is consistent with simple rules of integration of local inputs. These
      rules arise from known anatomical projection patterns in visual cortex. We
      propose that the generation and plasticity of orientation tuning is strongly
      influenced by local cortical networks-the diversity of these properties arises in
      part from the diversity of neighbourhood features that derive from the
      orientation map.

PMID- 16274975
TI  - Learning-induced modulation of oscillatory activities in the mammalian olfactory
      system: the role of the centrifugal fibres.
AB  - In the mammalian olfactory system, oscillations related to odour representation
      have been described in field potential activities. Previous results showed that
      in olfactory bulb (OB) of awake rats engaged in an olfactory learning, odour
      presentation produced a decrease of oscillations in gamma frequency range (60-90
      Hz) associated with a power increase in beta frequency range (15-40 Hz). This
      response pattern was strongly amplified in trained animals. The aim of this work
      was twofold: whether learning also induces similar changes in OB target
      structures and whether such OB response depends on its centrifugal inputs. Local
      field potentials (LFPs) were recorded through chronically implanted electrodes in
      the OB, piriform and enthorhinal cortices of freely moving rats performing an
      olfactory discrimination. Oscillatory activities characteristics (amplitude,
      frequency and time-course) were extracted in beta and gamma range by a wavelet
      analysis. First, we found that odour induced beta oscillatory activity was
      present not only in the OB, but also in the other olfactory structures. In each
      recording site, characteristics of the beta oscillatory responses were dependent
      of odour, structure and learning level. Unilateral section of the olfactory
      peduncle was made before training, and LFPs were symmetrically recorded in the
      two bulbs all along the acquisition of the learning task. Data showed that
      deprivation of centrifugal feedback led to an increase of spontaneous gamma
      activity. Moreover, under this condition olfactory learning was no longer
      associated with the typical large beta band. As a whole, learning modulation of
      the beta oscillatory response in olfactory structures may reflect activity of a
      distributed functional network involved in odour representation.

PMID- 16274973
TI  - Inhibitory synchrony as a mechanism for attentional gain modulation.
AB  - Recordings from area V4 of monkeys have revealed that when the focus of attention
      is on a visual stimulus within the receptive field of a cortical neuron, two
      distinct changes can occur: The firing rate of the neuron can change and there
      can be an increase in the coherence between spikes and the local field potential
      (LFP) in the gamma-frequency range (30-50 Hz). The hypothesis explored here is
      that these observed effects of attention could be a consequence of changes in the
      synchrony of local interneuron networks. We performed computer simulations of a
      Hodgkin-Huxley type neuron driven by a constant depolarizing current, I,
      representing visual stimulation and a modulatory inhibitory input representing
      the effects of attention via local interneuron networks. We observed that the
      neuron's firing rate and the coherence of its output spike train with the
      synaptic inputs was modulated by the degree of synchrony of the inhibitory
      inputs. When inhibitory synchrony increased, the coherence of spiking model
      neurons with the synaptic input increased, but the firing rate either increased
      or remained the same. The mean number of synchronous inhibitory inputs was a key
      determinant of the shape of the firing rate versus current (f-I) curves. For a
      large number of inhibitory inputs (approximately 50), the f-I curve saturated for
      large I and an increase in input synchrony resulted in a shift of sensitivity-the
      model neuron responded to weaker inputs I. For a small number (approximately 10),
      the f-I curves were non-saturating and an increase in input synchrony led to an
      increase in the gain of the response-the firing rate in response to the same
      input was multiplied by an approximately constant factor. The firing rate
      modulation with inhibitory synchrony was highest when the input network
      oscillated in the gamma frequency range. Thus, the observed changes in firing
      rate and coherence of neurons in the visual cortex could be controlled by top
      down inputs that regulated the coherence in the activity of a local inhibitory
      network discharging at gamma frequencies.

PMID- 16274976
TI  - [Archives de Pediatrie. Breast feeding: health benefits for child and mother.
      Editorial].

PMID- 16274977
TI  - [Modifier genes and cystic fibrosis].
AB  - Cystic fibrosis is the most common lethal autosomal recessive disease among the
      Caucasian population. It is caused by defects in the CFTR gene (Cystic Fibrosis
      Transmembrane Conductance Regulator). Although over 1600 disease-causing
      mutations in the CFTR gene have been described, the highly variable disease
      phenotype in cystic fibrosis cannot be explained on the basis of this gene alone.
      Both the environment and other non-CFTR genes are likely to be important. The
      increased understanding of pathophysiological processes in the cystic fibrosis
      lung has led to several studies on genes in these pathways. One of the major aims
      of such studies is to produce targets for novel drug developments.

PMID- 16274978
TI  - Haemolytic activity of maltopyranoside surfactants.
AB  - The haemolytic activity of a number of maltopyranoside surfactants was studied.
      The study included octyl, nonyl, decyl, dodecyl, tetradecyl, cyclohexyl-propyl,
      cyclohexyl-hexyl, and dimethyl-heptyl maltopyranoside. The in vitro haemolytic
      activity was determined by employing a static method in which surfactants are
      added to an erythrocyte suspension and the released haemoglobin is determined. It
      was found that alkyl maltopyranosides become more haemolytic the longer the alkyl
      chain. Branching or presence of cyclic groups clearly decreases haemolytic
      activity, but it also increases the critical micelle concentration. As a result,
      the cyclic or branched surfactants do not become better solubilizing excipients
      than the straight-chain surfactants. The most useful surfactant for
      pharmaceutical applications appears to be tetradecyl maltopyranoside, which is
      the least haemolytic surfactant relative to its critical micelle concentration.

PMID- 16274979
TI  - Gadolinium incorporated reconstituted chylomicron emulsion for potential
      application in tumor neutron capture therapy.
AB  - Gadolinium (Gd) neutron capture therapy (NCT) is currently under development as a
      potential approach for tumor therapy. Nanoparticles have been suggested as a
      potential delivery system to carry or target Gd to tumors for thermal or
      epithermal neutron irradiation. The reconstituted chylomicron emulsion is an
      artificial chylomicron remnant prepared using commercially available natural and
      biocompatible lipids. We proposed to use this nanometer-scale emulsion to deliver
      Gd to solid tumors by modifying the surface of the emulsion. A lipophilic Gd
      compound, gadolinium acetylacetonate (GdAcAc), was incorporated into the
      emulsion, resulting in a final pure Gd concentration of more than 1 mg/mL. The
      apparent solubility of GdAcAc was enhanced by about 6000-fold by this
      incorporation. The emulsion particles were shown to be stable in a two-week short
      term stability study when stored at 4 degrees C. In addition, no extensive
      particle aggregation was observed when the emulsion particles were incubated in
      simulated biological media such as serum. Also, GdAcAc does not significantly
      'leak' out from the emulsion particles. Only approximately 5% was released in 20
      h in a SDS (0.5% w/v) in phosphate buffered saline (pH 7.4, 10 mM) medium.
      Finally, the emulsion particles were coated with polyethylene glycol (PEG), and
      injected into Balb/C mice via the tail vein. A significant proportion (71.6 +/-
      18.4%) of the PEG-coated, GdAcAc-incorporated emulsion remained circulating in
      the blood 5 h after the injection, while the PEG-free emulsion was mainly
      accumulated inside the liver. This chylomicron emulsion may be used to deliver Gd
      into solid tumors for NCT.

PMID- 16274980
TI  - Cost-effectiveness analysis of budesonide/formoterol compared with fluticasone in
      moderate-persistent asthma.
AB  - In this economic evaluation, conducted alongside a randomized, double-blind
      clinical trial, economic data were collected from 339 patients with moderate
      persistent asthma randomized to receive twice-daily, double-blind treatment with
      budesonide/formoterol 160/4.5 microg in a single inhaler (n=166) or fluticasone
      propionate 250 microg (n=173) for 12 weeks. The mean number of episode-free days
      (EFD) per patient was significantly greater in the budesonide/formoterol group
      than the fluticasone group (48.71 compared with 42.34, P=0.0185). Data on
      medication use, visits to healthcare professionals, and hospitalization were
      pooled across all six countries and combined with German and Dutch unit cost data
      to calculate total healthcare costs. Using German unit costs,
      budesonide/formoterol was associated with significantly lower total healthcare
      costs per patient over the 12-week period compared with fluticasone (euro 131
      compared with euro 210, P=0.0043). Using Dutch unit costs, total healthcare costs
      were slightly numerically lower in the budesonide/formoterol group than the
      fluticasone group (euro 102 compared with euro 104), but the difference did not
      reach statistical significance. Budesonide/formoterol in a single inhaler is more
      effective than a higher microgram dose of fluticasone alone. It is cost-neutral
      and may provide cost-savings in some countries.

PMID- 16274981
TI  - Conversion of rice husk ash to zeolite beta.
AB  - White rice husk ash (RHA), an agriculture waste containing crystalline tridymite
      and alpha-cristobalite, was used as a silica source for zeolite Beta synthesis.
      The crystallization of zeolite Beta from RHA at 150 degrees C in the presence of
      tetraethylammonium hydroxide was monitored by XRD, FTIR and (29)Si MAS NMR
      techniques. It was found that zeolite Beta started to form after 12h and the
      complete crystallization of zeolite Beta phase was achieved after 2d. XRD, (29)Si
      MAS NMR and solid yield studies indicate that the transformation mechanism of
      silica present in RHA to zeolite Beta involves dissolution of the ash, formation
      of an amorphous aluminosilicate after 6h of crystallization, followed by
      dissolution in the mother liquor and final transformation to pure zeolite Beta
      crystals.

PMID- 16274982
TI  - Effect of compost treatment of sewage sludge on nitrogen behavior in two soils.
AB  - This work aims to evaluate the effects of compost treatment of digested sewage
      sludge on nitrogen behavior in two soils, a Spodosol and an Oxisol soil. Digested
      sewage sludge was composted with sawdust and woodchips, diluting the total
      nitrogen to one-fourth (dry mass basis) of its original value. Then, sludge and
      compost were added to the two soils on an equivalent dry weight basis to consider
      the risk of NO3- -N leaching. Compost treatment of sewage sludge has slowed down
      the release of mineral-N to half in the Spodosol and to one-third in Oxisol soil.
      As a result, NO3- -N concentrations in soils incubated with compost were less
      than half of the amounts found from soils incubated with digested sludge.
      Estimates were made of the maximum monthly nitrate to leach from the four
      combinations of soil and sludge treatment. Application of digested sludge, at a
      higher nitrogen application rate, resulted in a higher nitrate leaching potential
      than application of the compost product. Soil type also played an important role,
      with the Oxisol having slightly higher estimated leaching potential than the
      Spodosol. The higher nitrate release rate in the Oxisol is counterbalanced by its
      higher field capacity to lessen the expected difference between the two soils.

PMID- 16274983
TI  - Emotional communication in primates: implications for neurobiology.
AB  - The social brain hypothesis proposes that large neocortex size in Homonoids
      evolved to cope with the increasing demands of complex group living and greater
      numbers of interindividual relationships. Group living requires that individuals
      communicate effectively about environmental and internal events. Recent data have
      highlighted the complexity of chimpanzee communication, including graded facial
      expressions and referential vocalizations. Among Hominoids, elaborate facial
      communication is accompanied by specializations in brain areas controlling facial
      movement. Finally, the evolution of empathy, or emotional awareness, might have a
      neural basis in specialized cells in the neocortex, that is, spindle cells that
      have been associated with self-conscious emotions, and mirror neurons that have
      recently been shown to activate in response to communicative facial gestures.

PMID- 16274984
TI  - Enzymatic transition states and transition state analogues.
AB  - Transition states are the balance point of catalysis. Bonds are partially made
      and/or broken at the transition state, and the energy of the extended system
      provides near-equal probability that the system forms products or reverts to
      reactants. Enzymatic catalytic sites provide dynamic electronic environments that
      increase the probability that the transition state will be formed. Alignment of
      reactants in the Michaelis complex and motion of the catalytic site architecture
      are necessary to achieve the transition state. Transition state lifetimes are a
      fraction of a picosecond, preventing chemical equilibrium in extended covalent
      systems. Thus, dynamic descriptions of enzymatic transition states are required.
      Stable analogues similar to the transition state capture dynamic excursions that
      generate the transition state and convert them into thermodynamic binding energy.
      These analogues bind with extraordinary affinity relative to reactants.

PMID- 16274985
TI  - Conservative local treatment versus mastectomy after induction chemotherapy in
      locally advanced breast cancer: a randomised phase III study (EORTC 10974/22002,
      LAMANOMA)--why did this study fail?

PMID- 16274986
TI  - Space-time clustering patterns of gliomas in The Netherlands suggest an
      infectious aetiology.
AB  - To test the hypothesis that infectious exposures may be involved in glioma
      aetiology, we have analysed space-time clustering and seasonal variation using
      population-based data from the South of The Netherlands between 1983 and 2001.
      Knox tests for space-time interactions between cases were applied, with spatial
      coordinates of the addresses at time of diagnosis, and with distance to the Nth
      nearest neighbour. Data were also analysed by a second order procedure based on K
      functions. Tests for heterogeneity and Edwards' test for sinusoidal variation
      were applied to examine seasonal variation of incidence. There was statistically
      significant space-time clustering in the Eastern, but not in the Western part of
      the region. Clustering was only present in adults, particularly in less densely
      populated areas. There was no evidence for seasonal variation. The results
      support a role for infectious exposures in glioma aetiology that may act
      preferentially in certain geographical areas.

PMID- 16274987
TI  - Pre- and post-chemotherapy alkaline phosphatase levels as prognostic indicators
      in adults with localised osteosarcoma.
AB  - The prognostic value of alkaline phosphatase (AP) measured before and after
      chemotherapy, but before surgery was established in a retrospective survey of
      patients. The patients were 18 years or older, with non-metastatic high-grade
      osteosarcoma. Pre-chemotherapy AP was available in 89 cases, post-chemotherapy AP
      in 86 patients, and both in 71 cases. AP was classified as Normal (< 100% upper
      limit), High (100% < or = AP < 200%) or Very High (AP > or = 200%). Osteosarcoma
      subtype was predominantly conventional. No correlation was found between subtype
      and chemotherapy response, local recurrence or survival. Pre-chemotherapy AP was
      raised more in the osteoblastic subtype. Post-chemotherapy AP and normalisation
      were the same among different subtypes. AP was not correlated with local
      recurrence. Normal or High pre-chemotherapy AP correlated with better survival at
      10 years (64% and 70%) than Very High pre-chemotherapy AP (37%, P = 0.005). Post
      chemotherapy AP correlated with survival (68%, 39% and 25% in the Normal, High
      and Very High group, P = 0.0007) and response to chemotherapy (P = 0.049). A pre
      chemotherapy AP above twice Normal correlated with worse survival. If AP
      decreased after chemotherapy, but was still raised, survival was better, but
      still worse than if AP normalised. A raised post-chemotherapy AP predicts poor
      chemotherapy response.

PMID- 16274988
TI  - Effects of autoclaving and charcoal on root-promoting substances present in water
      extracts made from gelling agents.
AB  - The root-promoting ability of water extracts made from gelling agents (agar and
      Gelrite) was investigated using the mungbean rooting bioassay. Autoclaving these
      water extracts decreased the number of roots in mungbean cuttings compared to the
      controls. The addition of activated charcoal to the water extracts from Agar
      Bacteriological and Agar Commercial Gel had no effect on their root-promoting
      ability. Extracts with exogenous indole-3-butyric acid (IBA) which were treated
      by autoclaving or via a freeze-thaw cycle, significantly increased rooting.
      However, incorporation of activated charcoal to similar IBA-containing extracts
      reduced rooting. Our results indicate that more attention should be given to the
      choice of gelling agent and its interaction with other additives in the media
      used during tissue culture.

PMID- 16274989
TI  - Isolation and cholinesterase-inhibition studies of sterols from Haloxylon
      recurvum.
AB  - Haloxysterols A-D (1-4), new C-24 alkylated sterols, have been isolated from the
      chloroform soluble fraction of Haloxylon recurvum, along with five known sterols
      5-9, which are reported for the first time from this species. Their structures
      were determined by means of 1D- and 2D-NMR techniques. Compounds 1-9 inhibited
      cholinesterase enzymes in a concentration-dependent manner with K(i) values
      ranging between 0.85-25.5 and 1.0-19.0 microM against acetylcholinesterase (AChE;
      EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8) enzymes, respectively.
      Lineweaver-Burk, Dixon plots and their secondary replots indicated that compounds
      1-9 are non-competitive inhibitors of both AChE and BChE enzymes.

PMID- 16274990
TI  - Design and synthesis of 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4
      dihydro-1H-pyrano[3,4-b]benzofuran derivatives as non-nucleoside inhibitors of
      HCV NS5B RNA dependent RNA polymerase.
AB  - A novel class of HCV NS5B RNA dependent RNA polymerase inhibitors containing 3,4
      dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran
      scaffolds were designed and synthesized. Optimization of the alkyl substituent in
      the pyran ring showed preference for an n-propyl group, while 5,8-disubstitution
      pattern is preferred for the aromatic region. Analog 19 displayed potent activity
      with an IC(50) of 50 nM against HCV NS5B enzyme and was selective over a panel of
      polymerases.

PMID- 16274991
TI  - Characterization of high molecular weight impurities in synthetic
      phosphorothioate oligonucleotides.
AB  - Phosphorothioate oligonucleotides manufactured by standard phosphoramidite
      techniques using 2'-deoxyadenosine- or 2'-O-(2-methoxyethyl)-5-methylcytosine
      loaded solid supports contain branched impurities consisting of two chains linked
      through the exocyclic amino group of the 3'-terminal nucleoside of one chain and
      the 3'-terminal hydroxyl group of another via a P(O)SH group. These impurities
      are not produced when a universal, non-nucleoside derivatized support is used.

PMID- 16274992
TI  - Tethering identifies fragment that yields potent inhibitors of human caspase-1.
AB  - Disulfide Tethering was applied to the active site of human caspase-1, resulting
      in the discovery of a novel, tricyclic molecular fragment that selectively binds
      in S4. This fragment was developed into a class of potent inhibitors of human
      caspase-1. Several key analogues determined the optimal distance of the tricycle
      from the catalytic residues, the relative importance of various features of the
      tricycle, and the importance of the linker.

PMID- 16274993
TI  - Adjuvant endocrine therapies for pre-/perimenopausal women.
AB  - Endocrine therapy in the form of ovarian ablation was developed over a century
      ago. It remains nonetheless one of the most effective and most clearly targeted
      form of systemic therapy for breast cancer. Endocrine or hormonal therapy has an
      effect on virtually only those women whose tumors are positive for estrogen
      receptors (ER) and/or progesterone receptors (PgR). The presence of these steroid
      hormone receptors remains the most useful predictive factor in selecting therapy
      for breast cancer.

PMID- 16274994
TI  - The nursing practice of taking level 1 patient observations.
AB  - Nurses have a pivotal role in the early identification of patients at risk of
      deterioration through the taking of patient observations and assessment. This
      paper presents the findings from an ethnographic qualitative study to discover
      the practice of recording basic observations of general ward patients and
      discusses how these observations are used in the assessment of the physical state
      of the patient. The research is a triangulation method including participatory
      observation (n = 20) and semi-structured interviews (n = 8) of registered (n = 4)
      and unregistered (n = 4) nursing staff. Although the research is limited by its
      exploratory nature and the size of both the interview group and the observational
      study, the findings suggest that the experience of staff is important in the
      assessment of patients to detect indicators of patient deterioration. The
      practice of taking basic observations as a part of assessing patients has changed
      from being the qualified nurses' role to a role delegated to health care
      assistant. In addition, there appears to be a reliance on the use of electronic
      monitoring equipment. The results of the research will be utilised to inform
      where the practice might be improved.

PMID- 16274995
TI  - Biomimetic synthesis, antimicrobial, antileishmanial and antimalarial activities
      of euglobals and their analogues.
AB  - In the present communication, naturally occurring phloroglucinol-monoterpene
      adducts, euglobals G1-G4 (3b/a and 4a/b) and 16 new analogues (13a/b-18a/b and 19
      22) were synthesized by biomimetic approach. These synthetic compounds differ
      from natural euglobals in the nature of monoterpene and acyl functionality. All
      of these compounds were evaluated for their antibacterial, antifungal,
      antileishmanial and antimalarial activities. Analogue 17b possessed good
      antibacterial activity against methicillin-resistant Staphylococcus aureus, while
      analogues 19-22 possessed potent antifungal activity against Candida glabrata
      with IC50s ranging from 1.5 to 2.5 microg/mL. Euglobals along with all
      synthesized analogues exhibited antileishmanial activity. Amongst these, euglobal
      G2 (3a), G3 (4a) and analogues 13a and 14a showed potent antileishmanial activity
      with IC50s ranging from 2.8 to 3.9 microg/mL. Analogue 16a possessed antimalarial
      activity against chloroquine sensitive D6 clone of Plasmodium falciparum. None of
      the compounds showed toxicity against mammalian kidney fibroblasts (vero cells)
      upto the concentration of 4.76 microg/ml.

PMID- 16274996
TI  - Synthesis and biological evaluation of N-(7-indazolyl)benzenesulfonamide
      derivatives as potent cell cycle inhibitors.
AB  - We herein describe a new synthesis of N-(7-indazolyl)benzenesulfonamide
      derivatives. These compounds were evaluated for their antiproliferative
      activities toward L1210 murine leukemia cells. One of them, 4-methoxy-N-(3-chloro
      7-indazolyl)benzenesulfonamide, was identified as the most potent with an IC(50)
      of 0.44 microM.

PMID- 16274997
TI  - Fluorescently tagged iminoalditol glycosidase inhibitors as novel biological
      probes and diagnostics.
AB  - 1,5-Dideoxy-1,5-imino-D-glucitol, the corresponding D-manno and L-ido epimers as
      well as the powerful beta-glucosidase inhibitor isofagomine were N-alkylated with
      di-, tri-, as well as tetraethylene glycol derived straight chain spacer arms by
      a set of simple standard procedures. The terminal functional groups of the spacer
      arms, primary amines, were employed to introduce fluorescent dansyl moieties.
      Resulting derivatives showed glycosidase inhibitory activities comparable to
      those of the parent compounds'.

PMID- 16274999
TI  - Effects of atorvastatin on arterial endothelial function in coronary bypass
      surgery.
AB  - OBJECTIVE: Endothelial dysfunction represents a critical early component of organ
      injury following cardiopulmonary bypass. Recent studies demonstrate that the
      treatment with atorvastatin is associated with a significant improvement of
      endothelial function independently of its efficacy on cholesterol levels.
      Therefore, we investigated the effects of preoperative atorvastatin treatment on
      endothelium function after coronary surgery. METHODS: Forty patients undergoing
      coronary surgery were randomized to treatment with atorvastatin (20 mg/die; N=20)
      or placebo (N=20) 3 weeks before surgery. Twenty normal patients served as
      control group. The flow-mediated dilations (FMD) of the brachial artery after
      both reactive hyperemia (endothelium dependent) and nitroglycerin administration
      (endothelium independent) were evaluated at baseline, at 48 h, and 5 days
      postoperatively. RESULTS: At baseline, the endothelium-dependent FMD was
      significantly attenuated in coronary versus normal patients (normal 10.3+/-1.8%
      vs coronary 4.1+/-1.6%, p<0.01). At 48 h postoperatively all patients exhibited a
      reduced FMD compared with baseline values: the endothelium-dependent dilatation
      showed a drop of 60.1+15% in the patients of the placebo group compared with
      45.8+16.6% (p<0.05) those in the atorvastatin group. At the univariate analysis,
      no significant correlation was found between serum levels of either total
      cholesterol or HDL cholesterol and FMD. The nitroglycerin-induced dilation was
      not significantly influenced by extracorporeal circulation as well as by
      atorvastatin treatment. CONCLUSIONS: The endothelial dysfunction following
      cardiopulmonary bypass is improved by the treatment with atorvastatin, by a
      mechanism unrelated to the drug efficacy of controlling serum cholesterol levels.

PMID- 16274998
TI  - Selective up-regulation of the glial Na+-dependent glutamate transporter GLT1 by
      a neuroimmunophilin ligand results in neuroprotection.
AB  - Excessive accumulation of extracellular glutamate results in neuronal death.
      Termination of synaptic glutamate transmission and the prevention of
      excitotoxicity depend on rapid removal of glutamate by high affinity Na+
      dependent transporters. The astroglial transporter GLT1 is the predominant
      subtype, responsible for the bulk of extracellular clearance and for limiting
      excitotoxicity. This protein is crucial in the prevention of chronic glutamate
      neurotoxicity, and is markedly decreased in amyotrophic lateral sclerosis (ALS).
      Recent studies have shown that GLT1 expression can be induced in vitro and in
      vivo by various factors, but little is known about the signaling pathways
      mediating its regulation. The FK506-binding protein (FKBP) immunophilins are
      ubiquitous cytosolic proteins, concentrated in neural tissue
      (neuroimmunophilins). GPI-1046 is a synthetic, nonimmunosuppressive derivative of
      FK506 shown to exert neuroprotective and neuroregenerative actions in several
      systems. In the present study, we demonstrated that GPI-1046 induces selective
      expression of GLT1 in vitro and in vivo, associated with a marked increase in DHK
      sensitive Na+-dependent glutamate transport. Furthermore, treatment with GPI-1046
      was shown to protect motor neurons in an in vitro model of chronic
      excitotoxicity, and to prolong the survival of transgenic ALS mice. These studies
      suggest that neuroimmunophilins can regulate GLT1 and that their ligands could
      serve as therapies for neurodegenerative disorders.

PMID- 16275000
TI  - The ideal theoretical graft oversizing in valve-sparing aortic operations with a
      standard tubular or a Valsalva graft.
AB  - OBJECTIVE: We sought to determine, by a mathematical model, the ideal theoretical
      degree of ascending aortic graft oversizing needed to obtain normal sinuses
      dimension in the reimplantation type of valve-sparing aortic operations. METHODS:
      To define a normal-range value, size of sinuses of Valsalva was conventionally
      expressed as the area surrounding fully opened aortic cusps, the so-called beyond
      leaflets area (BLA), and measured in 50 healthy subjects. A mathematical
      relationship between aortic annulus diameter, aortic sinuses diameter and
      resulting BLA was defined. By simulating intra-operative scenarios, the effect of
      different degrees of a standard or Valsalva graft oversizing on BLA extension was
      tested. RESULTS: The same degree of graft oversizing resulted in a bigger beyond
      leaflets area for the Valsalva graft than for a standard graft. Oversizing
      degrees exceeding +7mm for a standard graft and +3mm for the Valsalva graft
      resulted in a beyond leaflets area over normal limits. Results were expressed in
      a visual form as two different normograms, one for the standard graft and one for
      the Valsalva graft. CONCLUSIONS: A less pronounced graft oversizing is needed to
      achieve normal-range sinuses size when using a Valsalva graft, the ideal
      theoretical graft oversizing was +7mm for a standard graft and +3mm for the
      Valsalva graft, our normograms can be helpful in selecting a proper graft size
      when performing a valve-sparing aortic procedure.

PMID- 16275001
TI  - Full metal jacket for thoracoabdominal aneurysm.

PMID- 16275002
TI  - A simplified technique for implantation of left ventricular epicardial leads for
      biventricular re-synchronization using video-assisted thoracoscopy (VATS).
AB  - OBJECTIVE: Cardiac re-synchronization therapy for treatment of heart failure
      requires transvenous insertion of both a right ventricular and left ventricular
      pacing lead. Implantation of the latter by way of the coronary sinus often fails.
      Therefore, alternative techniques for insertion are required. We applied a simple
      video-assisted surgical technique (VATS) using only two ports for the insertion
      of left-ventricular screw-in electrodes. METHODS: Fifteen patients (M: 10; F: 5;
      mean age: 62.2 years; range: 46-76 years) with heart failure meeting the ACC/AHA
      guidelines for implantation of biventricular pacing underwent transvenous
      insertion of the right atrial sensor lead and the right ventricular pacing lead.
      In all of them transvenous implantation of the left ventricular pacing lead
      failed, and they were planned for VATS. In right-lateral decubitus position and
      under single-lung ventilation a camera port and a flexible instrumentation port
      were inserted in the forth intercostal space. By using routine instruments, a T
      shaped incision was made lateral to the phrenic nerve and an electrode was
      screwed in. The lead was guided subcutaneously to the pacemaker. RESULTS: Mean
      skin-to-skin operating time was 55+/-16 min, no conversion to thoracotomy was
      necessary. All patients were extubated in the operating room and remained in the
      intensive care unit for less than 24h. Chest tubes were removed after a mean of
      1.6+/-0.5 days and the patients were discharged after a mean of 4+/-1.3 days.
      Intraoperative and postoperative pacing thresholds at 1 and 7 months were
      satisfactory in all cases and there was no lead dislocation. All but two patients
      had an improvement of their NYHA function class. There was neither surgical
      morbidity nor mortality. CONCLUSIONS: Video-assisted thoracoscopy over two ports
      seems to be an excellent alternative procedure for epicardial lead implantation.
      It is readily available and produces good pacing results at a short intervention
      time and tolerable stress for the patients.

PMID- 16275003
TI  - Old skills in a new context. But do we want to use it?

PMID- 16275004
TI  - Pulmonary resections in young octogenarians.

PMID- 16275006
TI  - Perioperative diagnosis of mesenteric ischemia in acute aortic dissection by
      transesophageal echocardiography.
AB  - OBJECTIVE: Although computed tomography, angiography, or magnetic resonance
      imaging is most commonly used for diagnosing mesenteric ischemia caused by acute
      aortic dissection, use of these modalities is often limited in the perioperative
      period. Thus, we have introduced transesophageal echocardiography to cover this
      deficit. Purpose of this study is to report the feasibility and accuracy of
      transesophageal echocardiographic diagnosis on mesenteric ischemia. METHODS: The
      consecutive 24 cases with acute aortic dissection which involved abdominal aorta
      and underwent surgery were examined. The celiac artery and superior mesenteric
      artery was visualized with 5 MHz biplane transesophageal echocardiography and was
      assessed for presence of dissection and blood flow in each of true and false
      lumen. The transesophageal echocardiographic findings were then correlated to the
      clinical course, computed tomographic findings, and laboratory data. RESULTS: The
      celiac artery and superior mesenteric artery was successfully visualized in 24
      cases (100%) and 23 cases (95.8%), respectively. Perfusion patterns in superior
      mesenteric artery were categorized into four patterns: (1) intact artery with
      adequate perfusion (type A: 14 cases); (2) dissection in the artery but with
      adequate perfusion in true lumen (type B: 5 cases); (3) dissection in the artery
      with narrowed true lumen compressed by false lumen without detectable blood flow
      (type C: 1 case); and (4) obstruction of arterial orifice by the intimal flap
      with narrowed true lumen in the proximal aorta (type D: 2 cases). One case with
      immediate postoperative death and another case with unsuccessful visualization of
      superior mesenteric artery were excluded from the analysis. Clinically apparent
      intestinal ischemia was present in three cases: one case with type C and two
      cases with type D, but in none of the remaining 19 cases with type A or type B
      (both sensitivity and specificity were 100%). The superior mesenteric artery was
      opacified in all of these three cases with ischemia. CONCLUSIONS: The
      transesophageal echocardiographic assessment is feasible in nearly all patients
      and potentially provides correct diagnosis on intestinal ischemia in the
      perioperative period of acute aortic dissection. Types C and D indicate
      significant mesenteric malperfusion.

PMID- 16275007
TI  - Importance of implant technique on risk of major paravalvular leak (PVL) after
      St. Jude mechanical heart valve replacement: a report from the Artificial Valve
      Endocarditis Reduction Trial (AVERT).
AB  - OBJECTIVE: To examine risk factors for major paravalvular leak (PVL) events after
      mechanical heart valve replacement. METHODS: We analyzed outcome of 807 patients
      randomized into the Artificial Valve Endocarditis Reduction Trial (AVERT). The
      mean follow-up time was 30.6 months and 21 major PVL events were reported. Three
      additional major PVL events associated with endocarditis were excluded from
      analysis. All baseline medical history variables, as well as operative parameters
      (including use of pledgets and suture technique) were examined using Cox
      regression. RESULTS: Major PVL was reported after 11 aortic, 9 mitral, and 1
      double valve replacement. 6/404 (1.5%) patients with conventional valves
      experienced a major PVL event versus 15/403 (3.7%) in the Silzone group. 10/172
      (5.8%) patients with valve suture technique without pledgets experienced a major
      PVL event versus 11/635 (1.7%) patients with pledgets. Final multivariable model
      showed that only suture technique without pledgets (p=0.005) was an independent
      significant risk factor for major PVL events. Silzone cuff showed a strong trend
      (p=0.055). CONCLUSIONS: Suture technique without pledgets is an independent
      significant risk factor for major PVL events. In this study, use of pledgets
      during valve replacement had a protective effect against subsequent paravalvular
      leak, supporting the use of buttress reinforcement for valve suture. The use of
      Silzone cuff, although not statistically significant, showed a strong trend as a
      risk factor.

PMID- 16275008
TI  - Effects of aprotinin on endothelium-dependent relaxation of large coronary
      arteries.
AB  - OBJECTIVE: Aprotinin is widely used in heart surgery for reduction of
      intraoperative blood loss. But recent reports presenting results from rat aorta
      experiments claimed that aprotinin selectively impairs endothelium-dependent
      relaxation (EDR) as well as basal NO availability in concentrations similar to
      doses routinely used in cardiovascular surgery. An impairment of coronary EDR by
      aprotinin would be a great danger for any cardiothoracic intervention. We
      therefore tested the influence of aprotinin in the coronary arteries of a non
      rodent species. METHODS: Fresh coronary arteries of pigs were obtained from the
      local slaughterhouse and transported to our laboratory in cold oxygenated Krebs
      Henseleit solution. Five-millimeter long rings were consecutively tested with or
      without aprotinin in concentrations of 500 KIU/ml (n=7) or 1000 KIU/ml (n=6) in
      oxygenated normothermic Krebs-Henseleit solution. PGF(2alpha) (10 micromol/l) was
      used for inducing contraction and substance P (10 nmol/l) for inducing EDR, which
      was calculated in percentage of the pre-contraction. Indomethacin (10 micromol/l)
      was added in all measurements to eliminate the influence of prostaglandins. In
      additional similar experiments (n=5), the influence of 1000 KIU/ml aprotinin on
      the EDR caused by the endothelium-derived hyperpolarizing factor (EDHF) was
      tested using l-NNA (300 micromol/l) to block all NO formation. RESULTS: The EDR
      of pig coronaries (82+/-5% or 80+/-5% of the pre-contraction in the control tests
      before and after aprotinin exposure) was not significantly changed by 500 KIU/ml
      aprotinin (78+/-7%). A small, but significant reduction of less than 1/10 of the
      EDR was induced by 1000 KIU/ml aprotinin (74+/-5%). After accounting for l-NNA
      for NO blockage, no aprotinin-related difference remained (59+/-6% vs 60+/-6% in
      controls). CONCLUSION: For clinically relevant concentrations of aprotinin up to
      500 KIU/ml, no significant reduction of the EDR can be found in epicardial
      coronary arteries of the pig. For higher doses of 1000 KIU/ml, a reduction in NO
      production seems to be the cause of the small but significant reduction of the
      EDR by aprotinin. Therefore, danger for impairment of coronary EDR by aprotinin
      at clinical dosage levels, as suggested by studies on rat aortas, seems to be
      absent in coronary arteries of a large mammalian model.

PMID- 16275009
TI  - Aortic root dilatation may alter the dimensions of the valve leaflets.
AB  - OBJECTIVE: Valve-sparing surgery can be used in patients with dilated aortic
      roots and aortic insufficiency (AI) but has not become a common practice, in part
      because the spared valve may be incompetent. Our goal was to study how the
      dimensions of the aortic root and leaflets have changed in such patients.
      METHODS: Fourteen patients with dilated aortic root and AI were examined by
      transesophageal echocardiography. The annulus diameter, sinotubular junction
      (STJ) diameter, sinus height, leaflet free-edge length, and leaflet height were
      measured. Correlations among these dimensions and with the AI grades were
      explored. Measurements were also made in 19 normal human aortic valves from
      silicone molds. RESULTS: There was no evident change in the average diameter of
      the annulus between the normal valves and those in the dilated aortic roots. The
      STJ diameter was obviously increased in the dilated aortic roots; the aortic
      sinuses also appeared to be taller and the leaflets larger than normal. The
      leaflet free-edge length, the leaflet height, and the sinus height were found to
      increase with the dilated STJ diameter. The degree of AI was not found to
      correlate well with any of the dimensions measured. CONCLUSIONS: The dimensions
      of the leaflets may change parallel to aortic root dilatation with AI. Therefore,
      during valve sparing, it may be necessary to correct both the dilatation of the
      root and the leaflet free-edge length to achieve a competent valve.

PMID- 16275010
TI  - Determination of the effectiveness of Pseudorabies marker vaccines in experiments
      and field trials.
AB  - The aim of vaccination in an eradication campaign is not only to induce clinical
      protection, but primarily to stop transmission of infections within and between
      herds by inducing herd immunity. Consequently, vaccines should be evaluated for
      their capacity to reduce virus transmission in the population. Glycoprotein E
      (gE) negative marker vaccines against Pseudorabies virus (PRV) infections in pigs
      have been evaluated this way in experiments and field studies. PRV infection in
      groups of (vaccinated) pigs was determined by measuring antibodies against gE of
      PRV from regularly taken serum samples. For the statistical analysis of the
      experiments a stochastic susceptible-infectious-removed (SIR) model was used. A
      measure for the transmission of virus is the reproduction ratio R, which is
      defined as the average number of secondary cases caused by one typical infectious
      individual. This implies that an infection will always fade out in a population
      when R < 1, but the infection can spread massively when R > 1. From several
      experiments it was shown that R < 1. Field studies showed that the R within herds
      was still > 1, but by reducing further contacts the R could be reduced to a value
      below one. This would imply that PRV could be eradicated by means of vaccination.
      In The Netherlands, an eradication campaign was launched in 1993, and in 2002 the
      virus was eradicated, as shown by a negligible number of gE-positive pigs.
      Farmers' organizations have to decide whether or not to stop vaccination.

PMID- 16275011
TI  - Randomized controlled trials with time-to-event outcomes: how much does
      prespecified covariate adjustment increase power?
AB  - PURPOSE: We evaluated the effects of various strategies of covariate adjustment
      on type I error, power, and potential reduction in sample size in randomized
      controlled trials (RCTs) with time-to-event outcomes. METHODS: We used Cox models
      in simulated data sets with different treatment effects (hazard ratios [HRs] = 1,
      1.4, and 1.7), covariate effects (HRs = 1, 2, and 5), covariate prevalences (10%
      and 50%), and censoring levels (no, low, and high). Treatment and a single
      covariate were dichotomous. We examined the sample size that gives the same power
      as an unadjusted analysis for three strategies: prespecified, significant
      predictive, and significant imbalance. RESULTS: Type I error generally was at the
      nominal level. The power to detect a true treatment effect was greater with
      adjusted than unadjusted analyses, especially with prespecified and significant
      predictive strategies. Potential reductions in sample size with a covariate HR
      between 2 and 5 were between 15% and 44% (covariate prevalence 50%) and between
      4% and 12% (covariate prevalence 10%). The significant-imbalance strategy yielded
      small reductions. The reduction was greater with stronger covariate effects, but
      was independent of treatment effect, sample size, and censoring level.
      CONCLUSIONS: Adjustment for one predictive baseline characteristic yields greater
      power to detect a true treatment effect than unadjusted analysis, without
      inflation of type I error and with potentially moderate reductions in sample
      size. Analysis of RCTs with time-to-event outcomes should adjust for predictive
      covariates.

PMID- 16275012
TI  - Estimating the incidence of dementia: the impact of adjusting for subject
      attrition using health care utilization data.
AB  - PURPOSE: To estimate incidence rates for dementia and the impact of subject
      attrition on these rates. METHODS: Crude, age- and gender-specific incidence
      rates of dementia and Alzheimer's disease were calculated using person-years
      analysis and Cox proportional hazard models in a population-based cohort study of
      1952 adults aged 65+ years in Manitoba, Canada. Rates were standardized to the
      nondemented population using the direct method. Ratios of incidence rates
      comparing completers to subjects who had died, refused, or were unavailable for
      follow up were based on health care utilization data (available for all subject
      groups) and used to adjust rates for attrition. RESULTS: Decedents had a
      significantly higher incidence of dementia than did subjects who completed the
      follow-up assessment. The incidence in subjects who refused or were unavailable
      at follow up was intermediate between decedents and completers. Adjusted for
      attrition, the standardized dementia incidence rate for community and
      institutional subjects was 25.3/1000 person-years, significantly higher than that
      based on follow-up assessments only (17.8/1000 person-years; 95% confidence
      interval: 14.3-21.4). CONCLUSIONS: The impact of loss to follow up on incidence
      rates varies depending on the reason for subject attrition. Incidence studies of
      dementia should develop strategies to characterize and address subject attrition
      to avoid underestimating disease incidence.

PMID- 16275014
TI  - Motor cortex excitability during unilateral muscle activity.
AB  - The effect of unilateral tonic muscle activity with and without co-activation of
      the antagonists on motor cortex excitability has been studied. Motor evoked
      potentials (MEPs) were recorded from the first dorsal interosseus muscles of both
      hands in response to transcranial magnetic stimulation (TMS) during relax,
      isometric index finger abduction and antagonistic co-activation. The
      intracortical inhibition (ICI) and intracortical facilitation (ICF) were
      investigated by paired-pulse TMS with interstimulus intervals of 3 and 13 ms. The
      unilateral tonic activation of the right hand facilitated contralateral and
      ipsilateral responses (cMEP and iMEP) recorded from both hands with an exception
      of iMEPs recorded from the left hand. During paired-pulse TMS ICI for cMEPs was
      not influenced by the unilateral tonic activity in both hands, while ICF was
      suppressed when MEPs were recorded from the active right hand. The effect of
      unilateral tonic activity on iMEP in response to paired-pulse TMS was essentially
      different: generally, ICI was greater for iMEPs and ICF was completely abolished
      with an exception of iMEPs recorded from the left hand during right finger
      isometric abduction when a strong ICF was evident. The decreased ICF and/or
      increased ICI are assumed to reflect mechanisms underlying the co-activation of
      antagonists.

PMID- 16275013
TI  - Effects of prenatal exposure to mercury on cognitive and psychomotor function in
      one-year-old infants: epidemiologic cohort study in Poland.
AB  - PURPOSE: The aim of the study is to assess the cognitive and psychomotor status
      of 1-year-old infants whose mothers were exposed to low, but varying, amounts of
      mercury during pregnancy. METHODS: Mercury levels in cord and maternal blood at
      delivery were used to assess prenatal environmental exposure to mercury. Bayley
      Scales of Infant Development were used to assess neurobehavioral health outcomes.
      The cohort consisted of 233 infants who were born at 33 to 42 weeks of gestation
      between January 2001 and March 2003 to mothers attending ambulatory prenatal
      clinics in the first and second trimesters of pregnancy. Enrollment included only
      nonsmoking women with singleton pregnancies between the ages of 18 and 35 years
      who were free from chronic diseases. RESULTS: The geometric mean (GM) for
      maternal blood mercury level for the group of infants with normal neurocognitive
      performance was lower (GM = 0.52 mug/L; 95% confidence interval [CI], 0.46-0.58)
      than that observed in the group with delayed performance (GM = 0.75 mug/L; 95%
      CI, 0.59-0.94), and this difference was significant (p = 0.010). The GM of cord
      blood mercury level in the normal group also was lower (GM = 0.85 mug/L; 95% CI,
      0.78-0.93) than that observed in the group with delayed performance (GM = 1.05
      mug/L; 95% CI, 0.87-1.27), and this difference was of borderline significance (p
      = 0.070). The relative risk (RR) for delayed performance increased more than
      threefold (RR = 3.58; 95% CI, 1.40-9.14) if cord blood mercury level was greater
      than 0.80 mug/L. Risk for delayed performance in the group of infants with
      greater maternal mercury levels (>0.50 mug/L) also was significantly greater (RR
      = 2.82; 95% CI, 1.17-6.79) compared with children whose mothers had mercury
      levels less than 0.50 mug/L. CONCLUSIONS: The results may be of public health
      importance because delayed psychomotor or mental performance in infants is
      assumed to be an indicator of later neurocognitive development in children, which
      may persist into adult life.

PMID- 16275015
TI  - Examination of extrinsic foot muscles during running using mfMRI and EMG.
AB  - Over-pronation has been cited as a key contributor to many types of running
      injuries. However, the roles of the extrinsic foot muscles during running have
      not been adequately identified. The purpose of this study was to examine the
      muscle functional (mf) MRI and EMG responses to perturbations of the foot by
      running in varus, neutral and valgus wedged shoes. Ten males ran at 3.6 m/s in
      specially constructed shoes for 5 min with T2-weighted mfMRI collected before and
      after each run. The change in T2 from before to after each run characterized the
      level of metabolic activity in each of muscle. Kinematic and EMG data were also
      collected while subjects ran on a treadmill. There were no T2 differences across
      the three shoe conditions. In contrast, there was significantly less EMG activity
      in the tibialis anterior and soleus while wearing the neutral shoe. Overall, the
      results did not support the theory that muscle activity would increase as the
      degree of eversion increased. It also appears that surface EMG was more sensitive
      to differences between conditions than mfMRI. However, this study illustrated
      that mfMRI may be a useful tool for quantifying muscle activity in cases where
      surface EMG is inadequate.

PMID- 16275016
TI  - Increased serotonin receptor availability in human sleep: evidence from an
      [18F]MPPF PET study in narcolepsy.
AB  - Data from animal studies suggest that serotonin release promotes wakefulness and
      suppresses REM sleep, but there are dangers in extrapolating these findings to
      humans. Binding of the radioligand [18F]MPPF to 5HT1A receptors is sensitive to
      levels of endogenous serotonin. In this study, we aimed to demonstrate changes in
      serotonin receptor availability in the human brain in wakefulness and sleep using
      [18F]MPPF and positron emission tomography. 14 subjects with narcolepsy cataplexy
      underwent [18F]MPPF PET scans in wakefulness and in sleep. Subjects who used the
      stimulant methylphenidate took their normal medication for the wake scan but
      omitted it prior to the sleep scan. The change in binding potential (BP) between
      the sleep and wake scans was examined using paired t test. Methylphenidate is
      thought to have little or no effect on serotonergic neurotransmission, and in
      order to confirm the absence of an effect on [18F]MPPF binding, a concurrent
      study was performed using a beta-microprobe technique to examine the effect of
      methylphenidate administration on [18F]MPPF binding in Sprague-Dawley rats. The
      human study showed a significant increase in [18F]MPPF binding in sleep compared
      to wakefulness in the whole brain and all regions of interest examined (temporal
      cortex, mesial temporal region and cingulate cortex). The beta-microprobe study
      confirmed that methylphenidate administration had no effect on [18F]MPPF binding.
      These findings indicate that serotonin receptor availability is increased in
      sleep compared to wakefulness in narcoleptic humans.

PMID- 16275017
TI  - Developmental changes in the neural correlates of semantic processing.
AB  - Functional magnetic resonance imaging (fMRI) was used to explore the neural
      correlates of semantic judgments in the auditory modality in a group of 9- to 15
      year-old children. Subjects were required to indicate if word pairs were related
      in meaning. Consistent with previous findings in adults, children showed
      activation in bilateral superior temporal gyri (BA 22) for recognizing spoken
      words as well as activations in bilateral inferior frontal gyri (BAs 47, 45) and
      left middle temporal gyrus (BA 21) for semantic processing. The neural substrates
      of semantic association and age differences were also investigated. Words with
      strong semantic association elicited significantly greater activation in the left
      inferior parietal lobule (BA 40), whereas words with weak semantic association
      elicited activation in left inferior frontal gyrus (BAs 47/45). Correlations with
      age were observed in the left middle temporal gyrus (BA 21) and the right
      inferior frontal gyrus (BA 47). The pattern of results for semantic association
      implies that the left inferior parietal lobule effectively integrates highly
      related semantic features and the left inferior frontal gyrus becomes more active
      for words that require a greater search for semantic associations. The
      developmental results suggest that older children recruit the right inferior
      frontal gyrus as they conduct a broader semantic search and the left middle
      temporal gyrus to provide more efficient access to semantic representations.

PMID- 16275019
TI  - Orientation-restricted continuous visual exposure induces marked reorganization
      of orientation maps in early life.
AB  - To elucidate the effect of visual experience on the development of orientation
      maps, we conducted intrinsic signal optical imaging of the visual cortex of
      kittens that were continuously exposed to a single orientation through
      cylindrical-lens-fitted goggles under a freely moving condition starting at post
      natal week 3. We observed a rapid reorganization of orientation maps,
      characterized by extensive representation of exposed orientations with reduced
      responsiveness to unexposed orientations. The over-representation of exposed
      orientation was marked for 1-2 weeks of goggle rearing. A longer period of goggle
      rearing, however, decreased the degree of over-representation, which still
      remained at a remarkable level. Dark rearing episodes daily interleaved between
      single orientation exposures moderated the over-representation effect. Unit
      recording from goggle-reared kittens showed preferred orientations consistent
      with optical imaging. Using c-Fos immunoreactivity mapping, we showed that the
      number of neurons strongly responding to the exposed orientation was 3 times
      larger in a goggle-reared cat than the number of neurons responding to the
      vertical orientation in a normal cat. Taken together, these results suggest that
      the reorganization of orientation maps was caused by the expansion of domains
      maximally responding to exposed orientation as well as the strong reduction of
      responses to unexposed orientations.

PMID- 16275018
TI  - Dissociable networks for the expectancy and perception of emotional stimuli in
      the human brain.
AB  - William James posited that comparable brain regions were implicated in the
      anticipation and perception of a stimulus; however, dissociable networks (at
      least in part) may also underlie these processes. Recent functional neuroimaging
      studies have addressed this issue by comparing brain systems associated with the
      expectancy and perception of visual, tactile, nociceptive, and reward stimuli. In
      the present fMRI study, we addressed this issue in the domain of pictorial
      emotional stimuli (IAPS). Our paradigm involved the experimental conditions
      emotional expectancy, neutral expectancy, emotional picture perception, and
      neutral picture perception. Specifically, the emotional expectancy cue was
      uncertain in that it did not provide additional information regarding the
      positive or negative valence of the subsequent picture. Neutral expectancy and
      neutral picture perception served as control conditions, allowing the
      identification of expectancy and perception effects specific for emotion
      processing. To avoid contamination of the perception conditions by the preceding
      expectancy periods, 50% of the pictorial stimuli were presented without preceding
      expectancy cues. We found that the emotional expectancy cue specifically produced
      activation in the supracallosal anterior cingulate, cingulate motor area, and
      parieto-occipital sulcus. These regions were not significantly activated by
      emotional picture perception which recruited a different neuronal network,
      including the amygdala, insula, medial and lateral prefrontal cortex, cerebellum,
      and occipitotemporal areas. This dissociation may reflect a distinction between
      anticipatory and perceptive components of emotional stimulus processing.

PMID- 16275020
TI  - Strategies for block-design fMRI experiments during task-related motion of
      structures of the oral cavity.
AB  - Functional MRI (fMRI) studies of jaw motion, speech, and swallowing disorders
      have been hampered by motion artifacts. Tissue motion perturbs the static
      magnetic field, creating geometric distortions in echo-planar images that lead to
      many false positives in activation maps. These problems have restricted blood
      oxygenation level-dependent (BOLD) fMRI studies involving orofacial muscles to
      event-related designs, which offer weak contrast-to-noise ratios when compared to
      block designs. Two new approaches are described that greatly reduce false
      positives in the activation maps created by the distortions in block-design fMRI
      studies involving jaw and tongue motion during chewing. First, an appropriate
      task duration of 10-14 s was found to maximize functional contrast while
      minimizing motion artifacts. Second, three motion-sensitive postprocessing
      methods were applied successively to examine the temporal and spatial
      characteristics of responses and identify and remove false positives caused by
      motion artifacts. These techniques are shown to allow the use of block design in
      an fMRI study of a jaw motion task. Extension to speech and swallowing tasks is
      discussed.

PMID- 16275021
TI  - Perceiving identical sounds as speech or non-speech modulates activity in the
      left posterior superior temporal sulcus.
AB  - The left superior temporal cortex shows greater responsiveness to speech than to
      non-speech sounds according to previous neuroimaging studies, suggesting that
      this brain region has a special role in speech processing. However, since speech
      sounds differ acoustically from the non-speech sounds, it is possible that this
      region is not involved in speech perception per se, but rather in processing of
      some complex acoustic features. "Sine wave speech" (SWS) provides a tool to study
      neural speech specificity using identical acoustic stimuli, which can be
      perceived either as speech or non-speech, depending on previous experience of the
      stimuli. We scanned 21 subjects using 3T functional MRI in two sessions, both
      including SWS and control stimuli. In the pre-training session, all subjects
      perceived the SWS stimuli as non-speech. In the post-training session, the
      identical stimuli were perceived as speech by 16 subjects. In these subjects, SWS
      stimuli elicited significantly stronger activity within the left posterior
      superior temporal sulcus (STSp) in the post- vs. pre-training session. In
      contrast, activity in this region was not enhanced after training in 5 subjects
      who did not perceive SWS stimuli as speech. Moreover, the control stimuli, which
      were always perceived as non-speech, elicited similar activity in this region in
      both sessions. Altogether, the present findings suggest that activation of the
      neural speech representations in the left STSp might be a pre-requisite for
      hearing sounds as speech.

PMID- 16275022
TI  - Application of an automated voxel-based morphometry technique to assess regional
      gray and white matter brain atrophy in a canine model of aging.
AB  - In recent years, voxel-based morphometry (VBM) has emerged as a technique to
      examine regional brain changes associated with normal and pathological aging.
      Despite its popularity in studies of human aging, application of VBM to animal
      models of brain aging is rare. In the present study, VBM techniques were
      developed to validate earlier region of interest (ROI) measures of brain aging in
      the dog and to provide a more comprehensive analysis of local changes in a canine
      model of brain aging. Consistent with previous findings, frontal lobe atrophy
      increased with age, most notably in aged male dogs. Age-related gray matter
      reductions were also observed in parietal and temporal lobes, thalamus,
      cerebellum, and brainstem. Temporal lobe atrophy was particularly prominent in
      old females. A number of age-related changes in white matter not previously
      explored in the dog were also identified with VBM. Specifically, aged males
      exhibited greater decreases in the internal capsula and cranial nerve bundles
      compared to decreased volumes in the alveus of the hippocampus in old female
      dogs. Together, the present results indicate that application of VBM techniques
      in a canine model of aging yields more comprehensive information regarding
      topographical patterns of brain aging in male and female dogs than previously
      reported using traditional manual ROI methods.

PMID- 16275025
TI  - Imidazole derivatives as antioxidants and selective inhibitors of nNOS.
AB  - The reperfusion of ischemic tissue often delays its physiological and functional
      recovery; this paradoxical effect is ascribed to increased release of free
      radicals including O(2)(-) and NO. For these reasons, scavenging reactive oxygen
      species or inhibition the NO synthesis has been shown to result in an enhanced
      neuronal survival after cerebral ischemia. Many authors believe that therapy for
      stroke patients would be a cocktail of drugs with various mechanisms of action.
      Combination therapy is a difficult and complicated avenue for drug development
      because of the possibility of drug-drug interactions. An alternative approach
      would be to combine multiple activities within the same compound. In
      consideration of the free-radical scavenging and inhibitory effect on NOS of
      various natural and synthetic compounds, the aim of this study was to analyze the
      antioxidant properties of some imidazole derivatives previously synthesized in
      our laboratory. Results obtained in the present study provide evidence that
      tested compounds exhibit interesting antioxidant properties, expressed either by
      their capacity to scavenge free radicals or their ability to reduce lipid
      peroxidation. In particular, compounds A and B represent chemical structures
      which can be easily modified to improve the observed antioxidant properties and
      to provide new therapeutic strategies focused on multiple downstream events.

PMID- 16275024
TI  - Patterns of nestin expression in human skin.
AB  - Nestin, a member of the sixth class of intermediate filament proteins, has long
      been known not only as a specific marker for central nervous system stem cells,
      but also as an indicator of the degree of neural stem cell differentiation.
      Immunohistochemical analysis showed nestin expression in the epidermis and the
      upper two-third of the hair follicle in non-balding human scalp skin, but not in
      the lower third of the follicle. Expression was very weak in the sebaceous gland.
      The level of nestin mRNA transcription was much higher in the bulge region of the
      follicle than in the sebaceous gland. These results show that the pattern of
      nestin expression is related to the differentiation of epidermal stem cells.

PMID- 16275026
TI  - Acrolein produces nitric oxide through the elevation of intracellular calcium
      levels to induce apoptosis in human umbilical vein endothelial cells:
      implications for smoke angiopathy.
AB  - Acrolein is a highly electrophilic alpha, beta-unsaturated aldehyde, the levels
      of which are increased in the blood of smokers. To determine if acrolein is
      involved in the pathology of smoke angiopathy, the effect of acrolein on human
      umbilical vein endothelial cells (HUVEC) was examined. Intracellular nitric oxide
      (NO) levels, determined using diaminofluorescein-2 diacetate (DAF-2 DA), an NO
      sensitive fluorescent dye, were found to be increased after treatment in HUVEC
      with 10 microM acrolein. The measurement of nitrite with 2,3-diaminonaphthalene
      and a Western blot analysis revealed that nitrite and S-nitroso-cysteine levels
      were increased in a dose-dependent manner, confirming that NO production is
      increased by acrolein. The increase was not reduced by treatment with 10mM N
      acetyl-l-cysteine (NAC), an anti-oxidant, but was reduced with 10 microM of the
      intracellular calcium chelator, 1,2-bis (o-aminophenoxy) ethane-N,N,N',N'
      tetraacetic acid tetra (acetoxymethyl) ester. Acrolein-stimulated NO production
      was significantly reduced by pretreatment with 1mM N(G)-nitro-l-arginine-methyl
      ester (L-NAME), an NO synthase inhibitor. The cytotoxicity of acrolein was
      reduced by pretreatment with 10 microM 2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO), an intracellular NO
      scavenger, or 1mM L-NAME, whereas it was not reduced by 10mM NAC, 20 microM
      Curcumin, another peroxide scavenger, or 100 microM Mn(III)TMPyP, a superoxide
      dismutase mimic. Nuclear staining and a Western blot analysis using an anti
      cleaved caspase 3 antibody revealed that the reduced viability of HUVEC by
      acrolein was due to apoptosis, which was reversed after pretreatment with 0.1mM
      carboxy-PTIO or 1mM L-NAME. Thus, acrolein increases intracellular calcium
      production to induce intracellular NO production by a calcium-dependent NO
      synthase, possibly eNOS, and the excess and rapid increase in NO might lead to
      the apoptosis of HUVEC. These data suggest that acrolein might be involved in the
      pathology of smoke angiopathy through the NO-induced apoptosis of endothelial
      cells.

PMID- 16275027
TI  - Cortico-hippocampal interaction and adaptive stimulus representation: a
      neurocomputational theory of associative learning and memory.
AB  - Computational models of the hippocampal region link psychological theories of
      associative learning with their underlying physiological and anatomical
      substrates. Our approach to theory development began with a broad description of
      the computations that depend on the hippocampal region in classical conditioning
      (Gluck and Myers, 1993 and Gluck and Myers, 2001). In this initial model, the
      hippocampal region was treated as an Information-processing system that
      transformed stimulus representations, compressing (making more similar)
      representations of inputs that co-occur or are otherwise redundant, while
      differentiating (or making less similar) representations of inputs that predict
      different future events. This model led to novel predictions for the behavioral
      consequences of hippocampal-region lesions in rodents and of brain damage in
      humans who have amnesia or are in the earliest stages of Alzheimer's disease.
      Many of these predictions have, since been confirmed by our lab and others.
      Functional brain imaging studies have provided further supporting evidence. In
      more recent computational modeling, we have shown how some aspects of this
      proposed information-processing function could emerge from known anatomical and
      physiological characteristics of the hippocampal region, including the entorhinal
      cortex and the septo-hippocampal cholinergic system. The modeling to date lays
      the groundwork for future directions that increase the depth of detail of the
      biological modeling, as well as the breadth of behavioral phenomena addressed. In
      particular, we are working now to reconcile these kinds of incremental
      associative learning models with other models of the hippocampal region that
      account for the rapid formation of declarative memories.

PMID- 16275028
TI  - Organ contouring for prostate cancer: interobserver and internal organ motion
      variability.
AB  - The purpose of this study is to assess the uncertainties that arise in locating
      the boundaries of anatomical structures, such as the prostate and the bladder,
      due to interobserver variability in the delineation of the structures and to
      internal organ motion. The variabilities are computed in all the radial
      directions and this information is used to obtain the margins, following the
      techniques and limitations imposed by medical practice. The margins obtained from
      the organ motions are significantly greater than those arising from interobserver
      variability. The developed tools, allow us to obtain the required margins in an
      efficient way.

PMID- 16275029
TI  - Probing membrane topology by high-resolution 1H-13C heteronuclear dipolar solid
      state NMR spectroscopy.
AB  - Membrane topology changes introduced by the association of biologically pertinent
      molecules with membranes were analyzed utilizing the (1)H-(13)C heteronuclear
      dipolar solid-state NMR spectroscopy technique (SAMMY) on magnetically aligned
      phospholipid bilayers (bicelles). The phospholipids (1)H-(13)C dipolar coupling
      profiles lipid motions at the headgroup, glycerol backbone, and the acyl chain
      region. The transmembrane segment of phospholamban, the antimicrobial peptide
      (KIGAKI)(3) and cholesterol were incorporated into the bicelles, respectively.
      The lipids (1)H-(13)C dipolar coupling profiles exhibit different shifts in the
      dipolar coupling contour positions upon the addition of these molecules,
      demonstrating a variety of interaction mechanisms exist between the biological
      molecules and the membranes. The membrane topology changes revealed by the SAMMY
      pulse sequence provide a complete screening method for analyzing how these
      biologically active molecules interact with the membrane.

PMID- 16275030
TI  - The pleckstrin homology domain of Gab-2 is required for optimal interleukin-3
      signalsome-mediated responses.
AB  - The adaptor protein Gab-2 coordinates the assembly of the IL-3 signalsome
      comprising Gab-2, Grb2, Shc, SHP-2 and PI3K. To investigate the role of the
      pleckstrin homology domain of Gab-2 in this process, epitope-tagged wild type Gab
      2 (WTGab-2), Gab-2 lacking its PH domain (DeltaPHGab-2) and the Gab-2 PH domain
      alone (PHGab-2) were inducibly expressed in IL-3-dependent BaF/3 cells.
      Expression of DeltaPHGab-2 reduced IL-3-dependent proliferation and long-term
      activation of ERK1 and 2 and PKB by IL-3. While we demonstrate that the Gab-2 PH
      domain can bind PI(3,4,5)P3, it is dispensable for Gab-2 membrane localisation,
      tyrosine phosphorylation and signalsome formation. Rather, the proline-rich
      motifs of Gab-2 appear to contribute to the constitutive membrane localisation we
      observe, independently of tyrosine phosphorylation or the PH domain. Taken
      together, these findings suggest that once Gab-2 is tyrosine phosphorylated its
      PH domain is required for the optimal stabilisation of the signalsome, enabling
      full activation of downstream signals.

PMID- 16275031
TI  - An evaluation of spherical designs for molecular-like surfaces.
AB  - The use of spherical harmonics in the molecular sciences is widespread. They have
      been employed with success in, for instance, the crystallographic fast rotation
      function, small-angle scattering particle reconstruction, molecular surface
      visualisation, protein-protein docking, active site analysis and protein function
      prediction. The calculation of spherical harmonic expansion coefficients requires
      integration over the full sphere and can be a computationally cumbersome and also
      numerically sensitive (with respect to the integration weights) procedure. It is
      shown here how the use of spherical t-designs and pre-computed near-equal weight
      integration layouts can significantly reduce the computational effort in the
      determination of spherical harmonic expansion coefficients for molecular
      surfaces, thus giving rise to a robust and highly efficient algorithm for the
      construction of molecular-like objects.

PMID- 16275023
TI  - Multiple maternal origins of chickens: out of the Asian jungles.
AB  - Domestic chickens have long been important to human societies for food, religion,
      entertainment, and decorative uses, yet the origins and phylogeography of
      chickens through Eurasia remain uncertain. Here, we assessed their origins and
      phylogeographic history by analyzing the mitochondrial DNA hypervariable segment
      I (HVS-I) for 834 domestic chickens (Gallus gallus domesticus) across Eurasia as
      well as 66 wild red jungle fowls (Gallus gallus) from Southeast Asia and China.
      Phylogenetic analyses revealed nine highly divergent mtDNA clades (A-I) in which
      seven clades contained both the red jungle fowls and domestic chickens. There was
      no breed-specific clade in the chickens. The clades A, B, and E are distributed
      ubiquitously in Eurasia, while the other clades were restricted to South and
      Southeast Asia. Clade C was mainly distributed in Japan and Southeast China,
      while clades F and G were exclusive to Yunnan, China. The geographic distribution
      of clade D was closely related to the distribution of the pastime of cock
      fighting. Statistical tests detect population expansion within each subclade.
      These distinct distribution patterns and expansion signatures suggest that
      different clades may originate from different regions, such as Yunnan, South and
      Southwest China and/or surrounding areas (i.e., Vietnam, Burma, and Thailand),
      and the Indian subcontinent, respectively, which support the theory of multiple
      origins in South and Southeast Asia.

PMID- 16275032
TI  - Conformational analyses and docking studies of a series of 5-nitrofuran- and 5
      nitrothiophen-semicarbazone derivatives in three possible binding sites of
      trypanothione and glutathione reductases.
AB  - To explore three possible binding sites of trypanothione and glutathione
      reductase, namely, the active, the dimer interface and the coenzyme NADPH binding
      site, a series of eight compounds, nitrofurans and nitrothiophenes derivatives,
      were docked, using their crystallographic and modeled conformations. Docking
      results showed that, for both families and both enzymes, compounds are more
      likely to bind in the interface site, even though there is some probability of
      binding in the active site. These studies are in agreement with experimental
      data, which suggest that these class of compounds can act either as uncompetitive
      or mixed type inhibitors, and also with the finding that there is an alpha-helix
      which connects the active with the interface site, thus allowing charge
      transference between them.

PMID- 16275033
TI  - Orlistat in the treatment of clozapine-induced hyperglycemia and weight gain.

PMID- 16275034
TI  - Council of Europe recommendation on human rights and psychiatry: a major
      opportunity for mental health services.

PMID- 16275035
TI  - Molecular cloning of two toxic phospholipases A2 from the crown-of-thorns
      starfish Acanthaster planci venom.
AB  - The full-length cDNAs encoding two toxic phospholipases A2 (AP-PLA2-I and -II)
      from the crown-of-thorns starfish Acanthaster planci venom were individually
      cloned by RT-PCR, 3'RACE and 5'RACE. In common with both AP-PLA2s, the precursor
      protein is composed of a signal peptide, a propeptide and a mature protein (136
      and 135 residues for AP-PLA2-I and -II, respectively). The four motifs (Ca2+
      binding loop, Ca2+-binding site, active site and catalytic network)
      characteristic of groups I and II PLA2s are well conserved in both AP-PLA2s. In
      addition to this, the presence of the elapid and pancreatic loops and the
      involvement of a propeptide in the precursors suggested that AP-PLA2s are highly
      analogous to the group IB PLA2s. However, when compared to the amino acid
      sequence of bovine pancreatic PLA2, the representative group IB PLA2, AP-PLA2s
      require some amino acid insertions and deletions in the region 76-100, as
      previously observed for the starfish Asterina pectinifera PLA2s. Furthermore, the
      phylogenetic tree made clearly demonstrated that AP-PLA2s and A. pectinifera
      PLA2s are distinguishable from the group IB PLA2s as well as other PLA2s, being
      classified into a new group.

PMID- 16275036
TI  - Expression in blood cells may contribute to biochemical and pathological
      improvements after neonatal intravenous gene therapy for mucopolysaccharidosis
      VII in dogs.
AB  - Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease due to
      deficient activity of beta-glucuronidase (GUSB) that results in accumulation of
      glycosaminoglycans in many organs. We have previously reported that neonatal
      intravenous injection of a gamma retroviral vector (RV) expressing canine GUSB
      resulted in transduction of hepatocytes, high levels of GUSB modified with
      mannose 6-phosphate in blood, and reduction in disease manifestations in the
      heart, bone, and eye. However, it was unclear if liver was the only site of
      expression, and the effect upon other organs was not assessed. We demonstrate
      here that blood cells from these RV-treated MPS VII dogs had substantial copies
      of RV DNA, and expressed the RNA at 2% of the level found in liver. Therefore,
      expression of GUSB in blood cells may synergize with uptake of GUSB from blood to
      reduce storage in organs. The RV-treated dogs had marked biochemical and
      pathological evidence of reduction in storage in liver, thymus, spleen, small
      intestines, and lung, and partial reduction of storage in kidney tubules. The
      brain had 6% of normal GUSB activity, and biochemical and pathological evidence
      of reduction in storage in neurons and other cell types. Thus, this neonatal gene
      therapy approach is effective and might be used in humans if it proves to be
      safe. Both secretion of enzyme into blood by hepatocytes, and expression in blood
      cells that migrate into organs, may contribute to correction of disease.

PMID- 16275037
TI  - Screening for tetrahydrobiopterin deficiencies using dried blood spots on filter
      paper.
AB  - Tetrahydrobiopterin (BH4) deficiency among newborns with hyperphenylalaninemia
      must be rapidly diagnosed and distinguished from classical phenylketonuria (PKU)
      to initiate immediately specific treatment and to prevent irreversible
      neurological damage. The characteristic pattern of urinary pterins makes it
      possible to differentiate between PKU and BH4 deficiencies, and to identify
      different variants of BH4 deficiency. However, collection, storage, and shipment
      of urine samples for pterin analysis is cumbersome. A method for the measurement
      of different pterins (neopterin, biopterin, and pterin) in blood collected on
      filter paper was developed as a potential alternative to the screening for BH4
      deficiencies in urine and for the monitoring of BH4 pharmacokinetics. Pterins
      pattern in blood spots was comparable with those in plasma and urine. We thus
      established reference values for pterins in blood spots in patients with
      hyperphenylalaninemia and identified new patients with GTP cyclohydrolase I
      deficiency, 6-pyruvoyl-tetrahydropterin synthase deficiency, and dihydropteridine
      reductase deficiency using dried blood spots on filter paper.

PMID- 16275038
TI  - Regulation of post-embryonic neuroblasts by Drosophila Grainyhead.
AB  - The Drosophila post-embryonic neuroblasts (pNBs) are neural stem cells that
      persist in the larval nervous system where they proliferate to produce neurons
      for the adult CNS. These pNBs provide a good model to investigate mechanisms
      regulating the maintenance and proliferation of stem cells. The transcription
      factor Grainyhead (Grh), which is required for morphogenesis of epidermal and
      tracheal cells, is also expressed in all pNBs. Here, we show that grh is
      essential for pNBs to adopt the stem cell programme appropriate to their position
      within the CNS. In grh mutants the abdominal pNBs produced more progeny while the
      thoracic pNBs, in contrast, divided less and produced fewer progeny than wild
      type. We investigated three candidates; the Neuroblast identify gene Castor, the
      signalling molecule Notch and the adhesion protein E-Cadherin, to determine
      whether they could mediate these effects. Neither Castor nor Notch fulfilled the
      criteria for intermediaries, and in particular Notch activity was found to be
      dispensable for the normal proliferation and survival of the pNBs. In contrast E
      Cadherin, which has been shown to regulate pNB proliferation, was present at
      greatly reduced levels in the grh mutant pNBs. Furthermore, ectopic expression of
      Grh was sufficient to promote ectopic E-Cadherin and two conserved Grh-binding
      sites were identified in the E-Cadherin/shotgun flanking sequences, arguing that
      this gene is a downstream target. Thus one way Grh could regulate pNBs is through
      expression of E-cadherin, a protein that is thought to mediate interactions with
      the glial niche.

PMID- 16275039
TI  - A cell cycle arrest is necessary for bottle cell formation in the early Xenopus
      gastrula: integrating cell shape change, local mitotic control and mesodermal
      patterning.
AB  - During development cell proliferation and morphogenetic movements are tightly
      intermingled. Both processes depend on the same cytoskeletal elements. Therefore,
      precise regulation of local mitotic activity seems to be basic for proper
      embryogenesis. Here, I report on bottle cells as an early non-mitotic cell
      population in the Xenopus gastrula. Endogenous and activin/BVg1-induced ectopic
      bottle cells do not proliferate. Overexpression of the mitosis-promoting
      phosphatase cdc25C increases the proliferation rate and interferes with bottle
      cell formation whereas the phosphatase-dead mutant cdc25C(C457A) does not. Cdc25C
      also affects other gastrulation processes such as epiboly, vegetal rotation or
      tissue separation as inferred from histological inspection of early gastrulae.
      Double stainings of gsc/Xbra transcripts and mitotic nuclei in ectopic and
      endogenous lips demonstrated that non-mitotic cells occur in the bottle cell
      region and, to a lesser extent, in the gsc domain which both are indicative of
      high TGF-beta signalling. In contrast, the Xbra-region and the remainder of the
      animal cap appear to be permissive for higher rates of cell proliferation. These
      data suggest inhibition of cell proliferation by high levels of activin-type
      signals and a close link of mesodermal and mitotic patterning. Finally,
      coexpression of eFGF together with activin/BVg1 interferes with TGF-beta-induced
      bottle cell formation. This inhibitory effect correlates with increased cell
      proliferation as compared to embryos injected with activin/BVg1 alone. Taken
      together, these data suggest that TGF-beta and FGF signals play antagonistic
      roles in bottle cell formation and the spatial control of the cell cycle in early
      Xenopus gastrulae.

PMID- 16275040
TI  - Longitudinal volumetric MRI study in first- and multiple-episode male
      schizophrenia patients.
AB  - In this longitudinal study we compared brain volume changes in first- and
      multiple-episode patients with schizophrenia to normal aging changes observed in
      healthy control subjects scanned at comparable times. Two to four years after an
      initial examination including MRI volumetry, we followed up 21 first episode
      patients, 17 patients after multiple episodes of schizophrenia, and 20 healthy
      controls. Volumetric measurements of left and right hemispheres, total brain
      volume, lateral ventricles, hippocampus and amygdala as well as a clinical
      evaluation were performed. Patients with schizophrenia showed significant
      ventricular enlargement and volume reduction of the hippocampus-amygdala complex
      compared with healthy control subjects both at baseline and follow-up. While
      there were no differences between patients and controls with respect to mean
      annual volume changes in the measured regions, patients with schizophrenia showed
      higher between-subject variability in ventricular volume change. These data are
      consistent with cross-sectional studies demonstrating ventricular enlargement and
      hippocampal volume deficits in schizophrenia. However, we were not able to
      demonstrate a difference in the rate of volume changes over time that
      distinguished patients with schizophrenia from healthy controls for any of the
      brain structures measured. Drawbacks of the study are that the follow-up was done
      after a relatively short interval and that there was a difference in time to
      follow-up and age between patients and controls. Our results do not support the
      hypothesis that schizophrenia leads to progressive volume reduction in these
      areas, although there may be a subset of patients with morphologically visible
      disease progression.

PMID- 16275041
TI  - Comparison of a low carbohydrate-low fiber diet and a moderate carbohydrate-high
      fiber diet in the management of feline diabetes mellitus.
AB  - This study compared the effects of a moderate carbohydrate-high fiber (MC-HF)
      food and a low carbohydrate-low fiber (LC-LF) food on glycemic control in cats
      with diabetes mellitus. Sixty-three diabetic cats (48 male castrated, 15 female
      spayed) were randomly assigned to be fed either a canned MC-HF (n = 32) food or a
      canned LC-LF (n = 31) food for 16 weeks. Owners were blinded to the type of diet
      fed. CBC, urinalysis, serum chemistry panel, fructosamine concentration and
      thyroxine concentration were determined on initial examination, and a complete
      blood count, serum chemistry panel, urinalysis and serum fructosamine
      concentration were repeated every 4 weeks for 16 weeks. Insulin doses were
      adjusted as needed to resolve clinical signs and lower serum fructosamine
      concentrations. Serum glucose (P = 0.0001) and fructosamine (P = 0.0001)
      concentrations significantly decreased from week 0 to week 16 in both dietary
      groups. By week 16, significantly more of the cats fed the LC-LF food (68%,
      22/31), compared to the cats fed the MC-HF food (41%, 13/32), had reverted to a
      non-insulin-dependent state (P = 0.03). Cats in both groups were successfully
      taken off of insulin regardless of age, sex, type of insulin administered or
      duration of clinical disease before entering the study. There was no significant
      difference in the initial or final mean body weights or in the mean change in
      body weight from week 0 to week 16 between dietary groups. Diabetic cats in this
      study were significantly more likely to revert to a non-insulin-dependent state
      when fed the canned LC-LF food versus the MC-HF food.

PMID- 16275042
TI  - Weights and measures: a new look at bisection behaviour in neglect.
AB  - Horizontal line bisection is a ubiquitous task in the investigation of visual
      neglect. Patients with left neglect typically make rightward errors that increase
      with line length and for lines at more leftward positions. For short lines, or
      for lines presented in right space, these errors may 'cross over' to become
      leftward. We have taken a new approach to these phenomena by employing a
      different set of dependent and independent variables for their description.
      Rather than recording bisection error, we record the lateral position of the
      response within the workspace. We have studied how this varies when the locations
      of the left and right endpoints are manipulated independently. Across 30 patients
      with left neglect, we have observed a characteristic asymmetry between the
      'weightings' accorded to the two endpoints, such that responses are less affected
      by changes in the location of the left endpoint than by changes in the location
      of the right. We show that a simple endpoint weightings analysis accounts readily
      for the effects of line length and spatial position, including cross-over
      effects, and leads to an index of neglect that is more sensitive than the
      standard measure. We argue that this novel approach is more parsimonious than the
      standard model and yields fresh insights into the nature of neglect impairment.

PMID- 16275043
TI  - Improved measles surveillance in Cameroon reveals two major dynamic patterns of
      incidence.
AB  - OBJECTIVE: To characterize the province-specific incidence patterns of measles in
      Cameroon and determine if an increase in measles incidence during the period
      January 2000-June 2001 is consistent with coincident epidemics in several regions
      with different inter-epidemic periods. METHOD: Periodic behavior of the monthly
      measles incidence time-series from each province of Cameroon was analyzed using
      time-series analysis and cluster techniques. Cumulative incidence in each
      province of Cameroon over a five-year period was associated with birth rates, and
      vaccination coverage. RESULTS: Distinct patterns of measles incidence were found
      in two different areas of Cameroon. The three northern-most provinces experience
      major epidemics every year. Seven southern provinces show evidence of
      experiencing major epidemics every third year. In January 2000, Cameroon
      experienced coincident peaks in these two cycles and thus an increase in measles
      incidence countrywide over the previous year. Higher cumulative province-specific
      incidence rates were associated with higher birth rates and lower routine
      vaccination coverage rates. CONCLUSION: Within one country, two dramatically
      different dynamic patterns of measles incidence were observed. Long-term
      surveillance data is crucial to the evaluation of measles immunization campaigns.
      The availability of a five-year record of measles incidence in Cameroon reveals
      an interesting dynamic pattern of measles incidence that accounts for the
      increase in countrywide incidence in 2000-2001.

PMID- 16275044
TI  - Assessment of hip protectors and corresponding hip fracture risk using stress
      calculation in the femoral neck.
AB  - As in many countries, a significant increase in the number of hip fractures is
      predicted due to the demographic changes in the population. To reduce the
      consequences for the patients and the social costs, hip protectors are considered
      to be effective in reducing the impact force on the hip and so to reduce the risk
      of hip fractures. The effectiveness of hip protectors has been investigated as
      well in experimental impact tests as in clinical studies, but there is still an
      uncertainty about their mechanical protection effect. Therefore, laboratory tests
      are an effective way to investigate the mechanical behaviour of hip protectors. A
      fracture is initiated by exceeding an ultimate compressive or tensile stress. In
      our model, stresses in the femoral neck are estimated by using the Euler beam
      formula. A standard femur was defined consisting of all mechanical parameters
      that have been identified to influence the mechanical resistance to external
      loads, such as the effective cross-sectional area (CSA), cross-sectional moment
      of inertia (CSMI), femoral neck width (FNW), centre of mass and other geometric
      parameters of the femur. In this study the necessary formulae as well as first
      results of assessing hip protectors on the basis of stresses in the femoral neck
      are presented. The results show that the methodology facilitates assessment and
      improvement of hip protectors, as the biomechanical parameters of real femora are
      the basis of the model.

PMID- 16275045
TI  - Temporal codes and sparse representations: a key to understanding rapid
      processing in the visual system.
AB  - Where neural information processing is concerned, there is no debate about the
      fact that spikes are the basic currency for transmitting information between
      neurons. How the brain actually uses them to encode information remains more
      controversial. It is commonly assumed that neuronal firing rate is the key
      variable, but the speed with which images can be analysed by the visual system
      poses a major challenge for rate-based approaches. We will thus expose here the
      possibility that the brain makes use of the spatio-temporal structure of spike
      patterns to encode information. We then consider how such rapid selective neural
      responses can be generated rapidly through spike-timing-dependent plasticity
      (STDP) and how these selectivities can be used for visual representation and
      recognition. Finally, we show how temporal codes and sparse representations may
      very well arise one from another and explain some of the remarkable features of
      processing in the visual system.

PMID- 16275047
TI  - Comparing objective and subjective status: gender and space (and environmental
      justice?).
AB  - The environmental justice literature has described differential health effects of
      environmental toxins and pollutants on people of different socio-economic status
      (SES) that may not always reflect differing levels of exposure. We offer four
      questions or contentions that together may contribute to understanding this
      conundrum and then present an empirical exploration of one of these questions:
      Does the relationship between SES and self-perceived status vary in space?
      Utilizing data from an original questionnaire survey of randomly selected adults
      conducted in twenty-five communities in British Columbia, Canada, a supplementary
      data set containing demographic and socio-economic characteristics of the
      communities themselves, and multilevel modelling techniques, this article
      describes relationships between objective and subjective measures of social
      status, by gender and in space. Our analysis contributes to the development of
      innovative environmental justice models by bringing some spatial sensitivity to
      interrelationships among these aspects of status.

PMID- 16275046
TI  - The selectivity of canary HVC neurons for the Bird's Own Song: rate coding,
      temporal coding, or both?
AB  - The neuronal selectivity observed in the avian song system for the Bird's Own
      Song progressively emerged as an extraordinary fruitful model to investigate the
      neural code underlying the recognition of complex stimuli and the occurrence of
      learned behaviors. In adult zebra finch, neurons from the HVC (used as a proper
      name) show very selective auditory responses, firing more to presentation of the
      Bird's Own Song (BOS) than to reverse BOS or other conspecific songs. However, as
      adult zebra finches always produce the same stereotyped song, the presence of
      such highly selective neurons in birds with larger repertoire still remains an
      open question. Data presented here show that neurons selective for the BOS can be
      found in adult canary, a seasonal breeding bird which display a large repertoire.
      More precisely, we found that a large proportion of neurons (29/36) exhibits
      higher responses to presentation of the forward than to the reverse BOS, and that
      22% of the cells were identified as selective on the basis of the d' value. For a
      cell that was extensively studied, we evaluated to what extent temporal stimulus
      related structure predicts the acoustic stimulus using linear or non-linear
      artificial neural networks (ANN). These analyses indicated that the temporal
      structure contained in spike trains characterizes more accurately the stimulus
      than the firing rate. The limitations of applying ANN analyses to
      electrophysiological data are discussed and potential solutions to increase the
      confidence in these analysis are proposed.

PMID- 16275048
TI  - [Tissular maternofetal immunization: new antigenic targets, new ideas].

PMID- 16275049
TI  - Dissolution rate improvement of poorly water-soluble drugs obtained by adsorbing
      solutions of drugs in hydrophilic solvents onto high surface area carriers.
AB  - The dissolution rate of the model drugs carbamazepine and nifedipine was improved
      by adsorbing solutions of the drugs in hydrophilic non-volatile or volatile
      solvents onto carriers with a large surface area. This was accomplished by
      dissolving the drug in methanol or the non-toxic hydrophilic liquids PEG 400 or 2
      pyrrolidone, and adsorbing these solutions onto the surface of silica (Aerosil)
      or crosslinked polyvinylpyrrolidone (Kollidon CL-M). The solvent binding
      capacities decreased in the order of methanol, PEG 400, 2-pyrrolidone for Aerosil
      200, 300, 380 and for Kollidon CL-M. Kollidon bound less liquid than Aerosil
      because of the smaller surface area. Differential scanning calorimetry
      measurements showed higher interactions between drugs and Kollidon compared to
      Aerosil, suggesting a low aggregation of precipitated drug particles. The drug
      release from the adsorbent systems was enhanced when compared to micronized drug
      and independent of the drug loading in the investigated range. The drugs were
      also dissolved in various liquid, paste-like or solid solubilisers (polyoxyl-40
      hydrogenated castor oil (Cremophor RH 40), macrogol-15-hydroxystearate (Solutol
      HS), poloxamers (Lutrol F68, Pluronic F87NF and Pluronic L44NF) and adsorbed onto
      Kollidon. These adsorbent systems also exhibited an increased dissolution rate
      when compared to pure drug.

PMID- 16275050
TI  - Chitosan drug binding by ionic interaction.
AB  - Three model drugs (insulin, diclofenac sodium, and salicylic acid) with different
      pI or pKa were used to prepare drug-chitosan micro/nanoparticles by ionic
      interaction. Physicochemical properties and entrapment efficiencies were
      determined. The amount of drug entrapped in the formulation influences zeta
      potential and surface charge of the micro/nanoparticles. A high entrapment
      efficiency of the micro/nanoparticles could be obtained by careful control of
      formulation pH. The maximum entrapment efficiency did not occur in the highest
      ionization range of the model drugs. The high burst release of drugs from
      chitosan micro/nanoparticles was observed regardless of the pH of dissolution
      media. It can be concluded that the ionic interaction between drug and chitosan
      is low and too weak to control the drug release.

PMID- 16275051
TI  - Microarray expression profiling resources for plant genomics.
AB  - Large volumes of genomic data have been generated for several plant species over
      the past decade, including structural sequence data and functional annotation at
      the genome level. Various technologies such as expressed sequence tags (ESTs),
      massively parallel signature sequencing (MPSS) and microarrays have been used to
      study gene expression and to provide functional data for many genes
      simultaneously. This review focuses on recent advances in the application of
      microarrays in plant genomic research and in gene expression databases available
      for plants. Large sets of Arabidopsis microarray data are publicly available.
      Recently developed array platforms are currently being used to generate genome
      wide expression profiles for several crop species. Coupled to these platforms are
      public databases that provide access to these large-scale expression data, which
      can be used to aid the functional discovery of gene function.

PMID- 16275052
TI  - High lung deposition of 99mTc-labeled ciclesonide administered via HFA-MDI to
      patients with asthma.
AB  - OBJECTIVE: To examine the deposition and pharmacokinetics of ciclesonide
      administered via hydrofluoroalkane-metered dose inhaler (HFA-MDI) in patients
      with asthma. METHODS: Twelve patients with mild asthma (FEV1, 95% predicted)
      inhaled a single dose of 99mtechnetium (Tc)-ciclesonide 320 microg ex-actuator
      (400 microg ex-valve). Deposition of ciclesonide in the lung and oropharynx was
      quantified using two-dimensional (2D)-gamma scintigraphy. Three-dimensional
      single photon emission computed tomography (3D SPECT) was used to assess the
      regional distribution of ciclesonide in the lung. The pharmacokinetics of
      ciclesonide and its active metabolite, desisobutyryl-ciclesonide (des-CIC), were
      determined by liquid chromatography-tandem mass spectrometry. Ciclesonide and des
      CIC concentrations were determined in mouth-rinsing solutions. RESULTS: 2D-gamma
      scintigraphy indicated that ciclesonide deposition was higher in the whole lung
      (52%) than in the oropharynx (32.9%). Furthermore, 3D SPECT revealed that
      ciclesonide deposition within the lungs was highest in the peripheral regions
      that contain the small airways and alveoli. The pharmacokinetic profile of Tc
      labeled ciclesonide and des-CIC was similar to that obtained after inhalation of
      non-labeled formulations in previous studies. Des-CIC accounted for 14.9% of the
      total molar concentration of ciclesonide/des-CIC in mouth-rinsing solutions
      obtained between 7 and 12min after inhalation. CONCLUSION: Inhalation of
      ciclesonide via HFA-MDI results in high pulmonary deposition, especially in the
      peripheral regions of the lung. High pulmonary deposition contributes to
      ciclesonide's ability to maintain lung function and control symptoms in patients
      with asthma. Deposition and activation of ciclesonide in the oropharynx is low,
      consistent with previous reports of low oropharyngeal deposition and a reduced
      incidence of local side effects in patients receiving ciclesonide therapy.

PMID- 16275053
TI  - The isolated perfused bovine retina--a sensitive tool for pharmacological
      research on retinal function.
AB  - The electroretinogram (ERG) of the isolated bovine retina serves as a proven
      criterion of retinal activity. It is used as a sensitive pharmacological tool for
      testing effects of applied drugs and toxins on photoreceptors, and higher order
      neurons that contribute to the generation of the b-wave. Following isolation and
      detachment from the underlying pigment epithelium, part of the retina was mounted
      into a closed chamber and perfused by a nutrient solution. Flow rate of the
      nutrient solution and its ingredients, incubation temperature and light intensity
      were optimised empirically to achieve a maximum b-wave amplitude. Under these
      conditions, a reproducible, high-resolution ERG can be stably recorded for more
      than 10 h with sufficient oxygenation found to be a prerequisite for the long
      lasting stability. Addition of L(+)glutamate to the nutrient solutions was not
      anymore beneficial for the b-wave amplitude. A well-known inhibitor of oxidative
      phosphorylation (KCN) and antagonists of voltage-gated Ca2+ channels (isradipine,
      omega-conotoxin-GVIA and NiCl2) were used to prove the validity of the test
      system. The recording of the ERG from the isolated and perfused bovine retina
      serves as a valuable physiological model for a neuronal network in which
      important questions related to the retinal signalling and metabolism can be
      investigated.

PMID- 16275054
TI  - Molecular imprinted ormosils for nafcillin recognition by room temperature
      phosphorescence optosensing.
AB  - Nafcillin imprinted sol-gels were used as specific binding materials for the room
      temperature phosphorescence (RTP) recognition of nafcillin using a flow injection
      system. Selective and reversible binding of the template to imprinted sol-gels
      could be observed by tailoring the hydrophobic/hydrophilic balance of the
      materials. Also, the possibility of minimizing non-specific interactions was
      evaluated by end-capping with trimethyl silyl groups. Control experiments were
      performed with non imprinted reference sol-gels. The recognition mechanism and
      the analytical potential of these materials for developing stable, selective and
      sensitive approaches for nafcillin recognition in real samples are outlined.

PMID- 16275055
TI  - Glucose biosensor based on Au nanoparticles-conductive polyaniline nanocomposite.
AB  - In this paper, we report a novel glucose biosensor based on composite of Au
      nanoparticles (NPs)-conductive polyaniline (PANI) nanofibers. Immobilized with
      glucose oxidase (GOx) and Nafion on the surface of nanocomposite, a sensitive and
      selective biosensor for glucose was successfully developed by electrochemical
      oxidation of H2O2. The glucose biosensor shows a linear calibration curve over
      the range from 1.0x10(-6) to 8.0x10(-4) mol/L, with a slope and detection limit
      (S/N=3) of 2.3 mA/M and 5.0x10(-7) M, respectively. In addition, the glucose
      biosensor system indicates excellent reproducibility (less than 5% R.S.D.) and
      good operational stability (over 2 weeks).

PMID- 16275056
TI  - Motor primitives in vertebrates and invertebrates.
AB  - In recent years different lines of evidence have led to the idea that motor
      actions and movements in both vertebrates and invertebrates are composed of
      elementary building blocks. The entire motor repertoire can be spanned by
      applying a well-defined set of operations and transformations to these primitives
      and by combining them in many different ways according to well-defined syntactic
      rules. Motor and movement primitives and modules might exist at the neural,
      dynamic and kinematic levels with complicated mapping among the elementary
      building blocks subserving these different levels of representation. Hence, while
      considerable progress has been made in recent years in unravelling the nature of
      these primitives, new experimental, computational and conceptual approaches are
      needed to further advance our understanding of motor compositionality.

PMID- 16275057
TI  - Clinical and pathological features of non-alcoholic steatohepatitis.
AB  - Clinical and pathological features were reviewed in 76 Japanese patients with non
      alcoholic steatohepatitis (NASH). Forty-one were male and 35 were female with the
      mean age of 49.7 years old (range 15-75 years old, males; 46.3, females; 53.7
      years old). Fifty-four percent of patients were preobese with a body mass index
      (BMI) between 25 and 30, while 16% of the patients were non-obese, and only 30%
      of the cases were morbidly obese, indicating that Japanese have a greater
      tendency to develop insulin-resistance and fatty liver disease than Western
      people. Hyperlipidemia was found in 51%, diabetes mellitus in 38%, and
      hypertension in 33% of the patients. Abnormally elevated liver function tests
      were found in one-third to two-thirds of the patients and were characteristically
      mild with 2- to 3-fold elevation from the normal range in the majority of the
      cases. Histological features of the liver were similar or identical to those
      reported in English literature and were characterized by fatty change,
      perivenular and pericellular fibrosis in zone 3, hepatocyte ballooning and
      necrosis with occasional Mallory's body formation and polymorphonuclear leukocyte
      infiltration. Mallory's bodies were found in 39% of patients and were
      characteristically small and poorly formed compared with those in alcoholic
      hepatitis. Eosinophilic granular or dirty foggy aggregated, not sufficient to be
      identified as Mallory's bodies, were a rather characteristic cytoplasmic
      expression in NASH patients. Portal inflammation and fibrosis were not found in
      the early stage of NASH, but were found as the disease progresses with formation
      of C-C and/or P-C bridging fibrosis, and eventually resulting in liver cirrhosis.

PMID- 16275058
TI  - Placenta growth factor is over-expressed and has prognostic value in human breast
      cancer.
AB  - Placenta growth factor (PlGF) belongs to the vascular endothelial growth factor
      (VEGF) family, a group of angiogenic factors that are crucial for tumour
      angiogenesis. Very little is known about the significance of PlGF in human
      cancer. We hypothesise that PlGF may have a potent influence in breast cancer.
      This study examined PlGF levels in human breast cancer in relation to patient's
      clinical parameters. PlGF expression and distribution was examined quantitatively
      using real-time quantitative polymerase chain reaction (Q-PCR) on a cohort of
      human breast cancer tissue (n = 119) and background breast tissue (n = 33),
      qualitatively using reverse transcriptase polymerase chain reaction (RT-PCR) on a
      range of cell lines, and immunohistochemically on patient samples. All these
      techniques revealed that PlGF expression was dramatically increased (P = 0.028)
      in breast cancer tissues compared with normal breast tissue. We demonstrate that
      PlGF displays prognostic value through analysis of patient survival status (6
      year follow-up), as elevated levels of PlGF were significantly associated (P =
      0.017) with recurrence, metastasis and patient mortality. Our study has shown
      that PlGF is over-expressed in breast cancer tissues and correlates with patient
      prognosis, and is likely to play a major role in the pathogenesis of tumours.

PMID- 16275059
TI  - Follow-up care for childhood cancer survivors: a focus group analysis.
AB  - Follow-up of survivors of childhood cancer is recommended to improve detection of
      late-effects, and provide individuals with information and advice. This study
      aimed to follow-up survivors of childhood cancer and report on their attitudes to
      current follow-up methods. Twenty-six survivors (13-25 years) of childhood cancer
      and their parent(s) attended focus groups (n = 7) to discuss views about follow
      up care. Transcripts were analysed using interpretative phenomenological analysis
      (IPA). Three themes were identified: strategies to achieve a normal life (through
      playing down possibility of late-effects or careful monitoring of health);
      expectations about follow-up (facts and information, advice about self-care,
      everyday living, and psychosocial consequences) and preferences for different
      models of care. Given that some families had reservations about the benefits of
      follow-up, it is important that services address survivors' interests and meet
      their expectations. Changes to service delivery must take account of individual
      needs and expectations. Possible limitations of focus group methods (recruitment,
      bias reduction, methods of analysis and influence of other participants' views)
      are discussed.

PMID- 16275060
TI  - Education: new approaches, new technologies and worldwide opportunities.

PMID- 16275061
TI  - Removal of organic pollutants from aqueous solutions by adsorbents prepared from
      an agroalimentary by-product.
AB  - Two series of crosslinked starch polymers were tested for their ability to adsorb
      organic pollutants in aqueous solutions. The polymers were prepared by a
      crosslinking reaction of starch-enriched flour using epichlorohydrin as the
      crosslinking agent, without and in the presence of NH(4)OH. These polymers were
      used as sorbent materials for the removal of phenolic derivatives from
      wastewater. The influence of several parameters (kinetics, pH and polymer
      structure) on the sorption capacity was evaluated using the batch and the open
      column methods. Results of adsorption experiments showed that the starch-based
      materials exhibited high sorption capacities toward phenolic derivatives. The
      study of the kinetics of pollutant uptake revealed that the adsorbents presented
      a relatively fast rate of adsorption. The experimental data were examined using
      the Langmuir and Freundlich models and it was found that the Freundlich model
      appeared to fit the isotherm data better than the Langmuir model.

PMID- 16275062
TI  - Removal of lead from aqueous solutions by agricultural waste maize bran.
AB  - Maize bran is a low cost biosorbent that has been used for the removal of
      lead(II) from an aqueous solution. The effects of various parameters such as
      contact time, adsorbate concentration, pH of the medium and temperature were
      examined. Optimum removal at 20 degrees C was found to be 98.4% at pH 6.5, with
      an initial Pb(II) concentration of 100 mg l(-1). Dynamics of the sorption process
      and mass transfer of Pb(II) to maize bran were investigated and the values of
      rate constant of adsorption, rate constant of intraparticle diffusion and the
      mass transfer coefficients were calculated. Different thermodynamic parameters
      viz., changes in standard free energy, enthalpy and entropy were evaluated and it
      was found that the reaction was spontaneous and exothermic in nature. The
      adsorption data fitted the Langmuir isotherm. A generalized empirical model was
      proposed for the kinetics at different initial concentrations. The data were
      subjected to multiple regression analysis and a model was developed to predict
      the removal of Pb(II) from an aqueous solution.

PMID- 16275063
TI  - Treatment of tomato processing wastewater by an upflow anaerobic sludge blanket
      anoxic-aerobic system.
AB  - The main objective of this study is to assess the achievability of stringent
      discharge criteria i.e. BOD(5)<15 mg/L, TSS<15 mg/L and NH(4)-N<1mg/L during the
      treatment of tomato processing wastewater with COD of 2800-15,500 mg/L, BOD(5) of
      1750-7950 mg/L, TKN of 48-340 mg/L and NH(4)-N of 21-235 mg/L. Two treatment
      systems, a UASB-aerobic system and a UASB-anoxic-aerobic system were tested.
      Furthermore due to alkalinity deficiency, in the raw wastewater, the study
      explored varying UASB effluent recirculation flowrates to the UASB influent to
      reduce additional alkalinity requirements. The UASB-anoxic-aerobic system was
      effective in treating tomato canning wastewater at an overall HRT of 1.75 days
      while achieving 98.5% BOD(5), 95.6% COD, 84% TSS and 99.5% NH(4)-N removal
      producing effluent BOD(5), COD, TSS, NH(4)-N, TKN, NO(2)-N, NO(3)-N and PO(4)-P
      of 10, 70, 15, 0.5, 3, 0, 60 and 4 mg/L, respectively. The biogas yield was 0.43
      m(3)/kg COD removed.

PMID- 16275064
TI  - Acute-phase reactants during murine tuberculosis: unknown dimensions and new
      frontiers.
AB  - SETTING: Serum amyloid P-component (SAP) plays important roles in host defense
      during various infectious diseases; however, nothing is known in tuberculosis
      (TB). OBJECTIVE: To study the SAP response of Mycobacterium tuberculosis H37Rv-
      and H37Ra-infected mice, and to determine the effect(s) of purified mouse SAP
      both on their intra-alveolar macrophage (AM) uptake and intra-AM growth in vitro.
      DESIGN: The SAP levels of mice intratracheally infected with M. tuberculosis
      H37Rv and H37Ra were determined by ELISA. Mycobacterial AM uptake and intra-AM
      growth in vitro were determined using fluorescence microscopy and plating,
      respectively. RESULTS: M. tuberculosis H37Rv-infected mice showed significantly
      (p < 0.05) increased SAP levels (352.8+/-36.1 microg/ml) with compared mice
      infected with M. tuberculosis H37Ra (170+/-18.5 microg/ml). During the acute
      phase of both these infections, enhanced SAP levels correlated with the lung
      mycobacterial load. In vitro, purified mouse SAP (1-80 microg/ml) inhibited the
      AM uptake of both the mycobacteria in a concentration-dependent manners to a
      similar extent; 20 microg/ml SAP appeared optimal. Mycobacterial uptake
      inhibition was divalent cation- and pH-dependent, and was unaffected both by heat
      inactivated and deglycosylated SAP, separately. Curiously, purified mouse SAP (1
      80 microg/ml), in a concentration-dependent manner, inhibited the intra-AM growth
      of both M. tuberculosis H37Rv and H37Ra in vitro; the effect was 0.8 log10 CFUs
      greater on the latter. Both the mannose-based simple sugars and rabbit anti-mouse
      SAP polyclonal antibody, separately, annulled the inhibition of mycobacterial
      growth in vitro. CONCLUSION: This initial study demonstrates that both the SAP
      response of M. tuberculosis-infected mice, and the SAP-induced intra-AM
      mycobacterial growth inhibition in vitro were apparently dependent on
      mycobacterial virulence.

PMID- 16275065
TI  - Synthesis and biological evaluation of gem-diamine 1-N-iminosugars related to L
      iduronic acid as inhibitors of heparan sulfate 2-O-sulfotransferase.
AB  - A variety of gem-diamine 1-N-iminosugars related to L-iduronic acid were
      synthesized and evaluated as inhibitors of heparan sulfate uronyl 2-O
      sulfotransferase using an in vitro enzyme assay. Two iminosugars containing
      guanidino groups acted as potent in vitro inhibitors of the enzyme.

PMID- 16275066
TI  - New potential antibacterials: a synthetic route to N-aryloxazolidinone/3
      aryltetrahydroisoquinoline hybrids.
AB  - A synthetic route to a new structural type of potential antibacterials, with a
      hybrid 3-aryltetrahydroisoquinoline-6,7-diol/N-aryloxazolidinone structure, is
      reported. The synthesis involves the successive construction of the 3
      aryltetrahydroisoquinoline and 4-substituted oxazolidinone moieties, the latter
      taking advantage of the functionalization at the para position of the aryl group.

PMID- 16275067
TI  - Synthesis of the tetrasaccharide side chain of the major glycoprotein of the
      Bacillus anthracis exosporium.
AB  - An alpha-glycoside of the tetrasaccharide sequence beta-Ant-(1-->3)-alpha-l-Rhap
      (1-->3)-alpha-l-Rhap-(1-->2)-alpha-l-Rhap whose aglycon allows conjugation to
      suitable carriers was synthesized. The NMR characteristics of the compound are
      virtually identical with those of the alpha-anomer of the tetrasaccharide
      isolated from the major glycoprotein of the Bacillus anthracis exosporium. Thus,
      the correct structure of the natural product has been proven by chemical
      synthesis.

PMID- 16275068
TI  - QSAR study for mycobacterial promoters with low sequence homology.
AB  - The general belief is that quantitative structure-activity relationship (QSAR)
      techniques work only for small molecules and, protein sequences or, more
      recently, DNA sequences. However, with non-branched graph for proteins and DNA
      sequences the QSAR often have to be based on powerful non-linear techniques such
      as support vector machines. In our opinion, linear QSAR models based on RNA could
      be useful to assign biological activity when alignment techniques fail due to low
      sequence homology. The idea bases the high level of branching for the RNA graph.
      This work introduces the so-called Markov electrostatic potentials (k)xi(M) as a
      new class of RNA 2D-structure descriptors. Subsequently, we validate these
      molecular descriptors solving a QSAR classification problem for mycobacterial
      promoter sequences (mps), which constitute a very low sequence homology problem.
      The model developed (mps=-4.664.(0)xi(M)+0. 991.(1)xi(M)-2.432) was intended to
      predict whether a naturally occurring sequence is an mps or not on the basis of
      the calculated (k)xi(M) value for the corresponding RNA secondary structure. The
      RNA-QSAR approach recognises 115/135mps (85.2%) and 100% of control sequences.
      Average predictability and robustness were greater than 95%. A previous non
      linear model predicts mps with a slightly higher accuracy (97%) but uses a very
      large parameter space for DNA sequences. Conversely, the (k)xi(M)-based RNA-QSAR
      encodes more structural information and needs only two variables.

PMID- 16275069
TI  - Synthesis and biological activities of nucleoside-estradiol conjugates.
AB  - Nucleosides were coupled to estradiol via a 17alpha-ethynyl spacer group using
      Pd(II) as a catalyst. The conjugates were evaluated in vitro for estrogen
      receptor (ER) binding affinity and cytotoxicity against cell lines with and
      without ER. The highest receptor binding affinities (RBA approximately 3) were
      observed with conjugates coupled via a relative long spacer group, while none of
      the conjugates exhibited cytotoxicity against either cell lines.

PMID- 16275070
TI  - Dipeptide-based highly potent doxorubicin antibody conjugates.
AB  - Highly potent and novel derivatives of doxorubicin were linked to monoclonal
      antibodies (mAbs) for site-specific drug delivery. Drug linker 5 consisted of a
      dipeptide linker attached directly to the daunosamine nitrogen of the n
      butyldiacetate doxorubicin derivative 2a. Upon hydrolysis of the peptide linker
      and acetate groups, the free daunosamine nitrogen is able to form the highly
      potent 2-pyrrolinodoxorubicin (3a). The second approach involved the use of an
      oxazolidine carbamate (13) to mask an activating aldehyde group until proteolytic
      hydrolysis releases 3a. Both drug linkers were shown to be substrates for the
      lysosomal enzyme cathepsin B. Each molecule was conjugated to the mAbs c1F6 (anti
      CD70) and cAC10 (anti-CD30) to give potent drug conjugates against renal cell
      carcinoma and anaplastic large cell lymphoma cell lines, respectively. The
      activities were immunologically selective, since antigen negative cell lines were
      much less sensitive to treatment with the drug conjugates. The approaches
      described here for attaching highly potent doxorubicin derivatives to mAbs are
      novel and allow for control of drug stability while covalently bound to the
      delivery agent.

PMID- 16275071
TI  - A new chemical tool for exploring the physiological function of the PDE2 isozyme.
AB  - Oxindole (2) is a potent and selective PDE2 inhibitor with a favorable ADME,
      physiochemical and pharmacokinetic profile to allow for use as a chemical tool in
      elucidating the physiological role of PDE2.

PMID- 16275072
TI  - N-(Aryl)-4-(azolylethyl)thiazole-5-carboxamides: novel potent inhibitors of VEGF
      receptors I and II.
AB  - Novel potent derivatives of N-(aryl)-4-(azolylethyl)thiazole-5-carboxamides are
      described as inhibitors of vascular endothelial growth factor receptor II (VEGFR
      2). Several compounds display VEGFR-2 inhibitory activity reaching IC(50)<100 nM
      in both enzymatic and cellular assays. The compounds also inhibit the related
      tyrosine kinase, VEGFR-1. By controlling the substitution pattern on the 5
      carboxamido pharmacophore, both dual and specific VEGFR-2 thiazoles were
      identified.

PMID- 16275073
TI  - Design, synthesis, and vasorelaxant and platelet antiaggregatory activities of
      coumarin-resveratrol hybrids.
AB  - We have synthesized the coumarin-resveratrol hybrid 4 and its dimethoxy
      derivative 3 by a very direct synthetic route involving a Pechmann procedure.
      Compound 4 has also been synthesized by an alternative route (Perkin), which also
      allowed the synthesis of compounds 9-13. In addition, we have evaluated the
      potential vasorelaxant activity of the new compounds in endothelium-containing
      rat aorta rings pre-contracted with noradrenaline, as well as the inhibitory
      effects on platelet aggregation induced by thrombin in washed human platelets.
      The compounds reported here relaxed vascular smooth muscle and inhibited platelet
      aggregation with a profile similar to that of trans-resveratrol (t-RESV) and, in
      some cases, showed activity higher than that of the natural compound. This is the
      case for compound 13, which has a vasorelaxant activity that is twice as high as
      that of t-resveratrol and a platelet antiaggregant activity that is six times
      higher. These results suggest that these novel compounds may have potential as
      structural templates for the design and subsequent development of new
      vasodilatory and platelet antiaggregatory drugs.

PMID- 16275074
TI  - Metalloantimalarials: synthesis, X-ray crystal structure of potent antimalarial
      copper (II) complex of arylazo-4-hydroxy-1,2-naphthoquinone.
AB  - The crystal structure of copper (II) complex of 3-arylazo-4-hydroxy-1,2
      naphthoquinone is reported. The in vitro antimalarial activity of analogous
      compounds against Plasmodium falciparum 3D7 strain reveals correlation with metal
      redox couple, suggesting component of parasitic electron transport chain as a
      possible target.

PMID- 16275075
TI  - 5-heteroatom substituted pyrazoles as canine COX-2 inhibitors. Part 1: Structure
      activity relationship studies of 5-alkylamino pyrazoles and discovery of a
      potent, selective, and orally active analog.
AB  - Structure-activity relationship (SAR) studies of the novel 2-[3-di and
      trifluoromethyl-5-alkylamino pyrazo-1-yl]-5-methanesulfonyl (SO(2)Me)/sulfamoyl
      (SO(2)NH(2))-pyridine derivatives for canine COX enzymes are described. The
      studies led to the identification of 2e as lead with potent in vitro activity,
      selectivity, and in vivo activity in dogs and cats.

PMID- 16275077
TI  - Design and synthesis of substituted phenylpropanoic acid derivatives as human
      peroxisome proliferator-activated receptor alpha/delta dual agonists.
AB  - A series of phenylpropanoic acids was prepared as candidate dual agonists of
      peroxisome proliferator-activated receptors (PPAR) alpha and delta. Structure
      activity relationship studies indicated that the shape of the linker moiety and
      the nature of the substituent at the distal benzene ring play key roles in
      determining the potency and selectivity of PPAR subtype transactivation.
      Optically active alpha-ethylphenylpropanoic acid derivatives were identified as
      potent human PPAR alpha and delta dual agonists with potential for the treatment
      of metabolic syndrome.

PMID- 16275076
TI  - Pyrrolopyridazine MEK inhibitors.
AB  - The synthesis and SAR of a series of pyrrolopyridazine MEK inhibitors are
      reported. Optimal activity was achieved by incorporation of a 4-phenoxyaniline
      substituent at C4 and an acylated amine at C6.

PMID- 16275078
TI  - Synthesis and antiviral activity of 7-deazaneplanocin A against orthopoxviruses
      (vaccinia and cowpox virus).
AB  - An efficient method for the synthesis of 7-deazaneplanocin A (2) has been
      accomplished by the condensation of cyclopentenol 3 with 6-chloro-7-deazapurine
      followed by subsequent functional group manipulations. The synthesized 7
      deazaneplanocin A (2) exhibited potent antiviral activity against cowpox and
      vaccinia viruses without cytotoxicity in HFF cells.

PMID- 16275079
TI  - 4-substituted cyclohexyl sulfones as potent, orally active gamma-secretase
      inhibitors.
AB  - The protease gamma-secretase plays a pivotal role in the synthesis of pathogenic
      amyloid-beta in Alzheimer's disease (AD). Here, we report a further extension to
      a series of cyclohexyl sulfone-based gamma-secretase inhibitors which has allowed
      the preparation of highly potent compounds which also demonstrate robust
      Abeta(40) lowering in vivo (e.g., compound 32, MED 1mg/kg p.o. in APP-YAC mice).

PMID- 16275081
TI  - Acryloylamino-salicylanilides as EGFR PTK inhibitors.
AB  - A series of acryloylamino-salicylanilides were synthesized as inhibitors of EGFR
      PTK. A strategy of pseudo six-membered ring formed through intramolecular
      hydrogen bonding in salicylanilides is employed to mimic the planar pyrimidine
      ring of quinazoline EGFR inhibitors. Acrylamido moiety is incorporated to target
      the Cys-773 of EGFR specifically. Some of the obtained compounds exhibited good
      activity as EGFR inhibitors.

PMID- 16275080
TI  - Substituted indanylacetic acids as PPAR-alpha-gamma activators.
AB  - A series of oxazole-substituted indanylacetic acids were prepared which show a
      spectrum of activity as ligands for PPAR nuclear receptor subtypes.

PMID- 16275082
TI  - WITHDRAWN: Derivatives of cis-1,2,3,6-tetrahydrophthalimide for the treatment of
      benign prostatic hyperplasia.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 16275084
TI  - New tyrosinase inhibitors selected by atomic linear indices-based classification
      models.
AB  - In the present report, the use of the atom-based linear indices for finding
      functions that discriminate between the tyrosinase inhibitor compounds and
      inactive ones is presented. In this sense, discriminant models were applied and
      globally good classifications of 93.51% and 92.46% were observed for non
      stochastic and stochastic linear indices best models, respectively, in the
      training set. The external prediction sets had accuracies of 91.67% and 89.44%.
      In addition, these fitted models were used in the screening of new cycloartane
      compounds isolated from herbal plants. A good behavior is shown between the
      theoretical and experimental results. These results provide a tool that can be
      used in the identification of new tyrosinase inhibitor compounds.

PMID- 16275083
TI  - Isolation and inhibitory activity against ERK phosphorylation of
      hydroxyanthraquinones from rhubarb.
AB  - Five hydroxyanthraquinone compounds were purified from Chinese medicinal herb
      rhubarb by microwave-assisted extraction and silica gel column isolation. Their
      structures were identified by spectroscopic analysis. One of them, emodin, was
      found to block the ERK phosphorylation of PC3 cells at 20 microM. And two other
      compounds had potent proliferation inhibitory activity on A431 and PC3 cells at
      20 microM. Furthermore, crude extracts revealed an antifungal activity stronger
      than that of purified compounds against several plant pathogens tested. Together,
      our study suggests that these compounds are biologically active and may lead to
      development of anticancer medicine.

PMID- 16275085
TI  - Synthesis and biological evaluation of biphenylsulfonamide carboxylate
      aggrecanase-1 inhibitors.
AB  - Aggrecanases are recently discovered enzymes that cleave aggrecan, a key
      component of cartilage. Aggrecanase inhibitors may provide a unique means to halt
      the progression of cartilage destruction in osteoarthritis. The synthesis and
      evaluation of biphenylsulfonamidocarboxylic acid inhibitors of aggrecanase-1 are
      reported. Compound 24 demonstrated 89% inhibition of proteoglycan degradation at
      10 microg/mL and has an oral bioavailability in rat of 35%.

PMID- 16275086
TI  - Synthesis and biological activity of the first cyclic biphalin analogues.
AB  - Biphalin is a linear octapeptide with strong opioid activity. Its structure is
      based on two identical sequences derived from enkephalins joined C-terminal to C
      terminal by an hydrazide bridge (Tyr-D-Ala-Gly-Phe-NH-NH<--Phe<--Gly<--D-Ala<-
      Tyr). In this study we present the design, synthesis, and biological evaluation
      of the first cyclic biphalin analogues. d-Alanine residues in positions 2, 2' of
      the parent peptide were replaced by d- and l-cysteine and an intramolecular
      disulfide bond between the cysteine thiol groups was introduced. We obtained two
      cyclic analogues with quite different biological profiles.

PMID- 16275087
TI  - Potent anti-muscarinic activity in a novel series of quinuclidine derivatives.
AB  - The synthesis and biological evaluation of a novel family of M(3) muscarinic
      antagonists are described. A systematic modification of the substituents to a
      novel alkyne-quinuclidine scaffold yielded original compounds displaying potent
      in vitro anticholinergic properties.

PMID- 16275088
TI  - 8-(1-Naphthalen-2-yl-vinyl)-6,7,10-trioxaspiro (4.5) decane, a new 1,2,4-trioxane
      effective against rodent and simian malaria.
AB  - A new series of 8-(1-aryl-vinyl)-6,7,10-trioxaspiro [4.5] decanes 7a-e and 3-(1
      aryl-vinyl)-l,2,5-trioxaspiro [5.5] undecanes 8a-e have been prepared and
      screened against multi-drug resistant Plasmodium yoelii in mice. 8-(1-Naphthalen
      2-yl-vinyl)-6,7,10-trioxaspiro [4.5] decane 7b, the most active trioxane of the
      series, has also shown promising activity against Plasmodium cynomolgi in rhesus
      monkeys.

PMID- 16275089
TI  - Design, synthesis, and anti-Helicobacter pylori activity of erythromycin A (E)-9
      oxime ether derivatives.
AB  - The synthesis and anti-Helicobacter pylori (H. pylori) activity evaluation of a
      new series of erythromycin A (E)-9-oxime ether derivatives are described. These
      compounds exhibited comparable in vitro anti-H. pylori activity and improved acid
      stability compared to the reference compound clarithromycin.

PMID- 16275090
TI  - Novel 1,3-dipropyl-8-(1-heteroarylmethyl-1H-pyrazol-4-yl)-xanthine derivatives as
      high affinity and selective A2B adenosine receptor antagonists.
AB  - A series of new 1,3-dipropyl-8-(1-heteroarylmethyl-1H-pyrazol-4-yl)-xanthine
      derivatives as A(2B)-AdoR antagonists have been synthesized and evaluated for
      their binding affinities for the A(2B), A(1), A(2A), and A(3)-AdoRs. 8-(1-((3
      phenyl-1,2,4-oxadiazol-5-yl)methyl)-1H-pyrazol-4-yl)-1,3-dipropyl-1H-purine
      2,6(3H,7H)-dione (4) displayed high affinity (K(i)=1 nM) and selectivity for the
      A(2B)-AdoR versus A(1), A(2A), and A(3)-AdoRs (A(1)/A(2B), A(2A)/A(2B), and
      A(3)/A(2B) selectivity ratios of 370, 1100, and 480, respectively). The synthesis
      and SAR of this novel class of compounds are presented herein.

PMID- 16275091
TI  - Neurotrophic factors in relapsing remitting and secondary progressive multiple
      sclerosis patients during interferon beta therapy.
AB  - Although interferon (IFN) beta is a widely used disease-modifying therapy in
      multiple sclerosis (MS), the mechanisms responsible for its effects are not fully
      understood. Some studies demonstrated that IFNbeta induces nerve growth factor
      (NGF) secretion by astrocytes and by brain endothelial cells. In this study, we
      determined the production of various neurotrophins (brain-derived neurotrophic
      factor, BDNF; NGF; glial cell line-derived neurotrophic factor; neurotrophin 3;
      neurotrophin 4) by peripheral blood mononuclear cells (PBMCs) in relapsing
      remitting (RR) and secondary progressive (SP) MS patients during IFNbeta
      treatment. There were no main variations in neurotrophin production either among
      all MS patients globally considered or in the group of SPMS subjects. Instead, in
      the group of RRMS patients who did not present clinical exacerbation of disease
      up to the end of the study, we found a significant increase in BDNF production as
      from 6 months after starting therapy.

PMID- 16275092
TI  - Minimally invasive surgical techniques for stress incontinence surgery.
AB  - Minimally invasive techniques for surgical correction of stress incontinence date
      back to the late 1950s. Since that time there have been many developments to
      attempt to emulate the good results achieved by open surgery with less surgical
      morbidity. Needle suspensions have attempted to reposition the bladder neck in
      the same way as a colposuspension. However, although numerous variations have
      been described, they do not have the long-term outcomes of colposuspension. These
      variations, their complications and long-term outcome are discussed. Sling
      surgery, especially the tension-free vaginal tape (TVT), has probably had the
      largest impact on incontinence surgery in recent years, offering a procedure with
      low morbidity and, thus far in the medium term, outcomes comparable with those of
      more invasive procedures. This has led the TVT procedure to become the most
      common procedure performed worldwide for stress incontinence. With the benefit of
      lessons learnt from the use of synthetic material in the genitourinary tract,
      some worries remain with regard to the long-term complications of TVT. Other non
      synthetic material should not be forgotten, and the advantages and disadvantages
      of various sling materials are compared. Injectables have an established place in
      the treatment of sphincter deficiency, though long-term results are poor compared
      to those of other procedures. Various materials used and the technique for their
      injection are discussed.

PMID- 16275093
TI  - Pelvic anatomy and MRI.
AB  - An in-depth knowledge of the anatomy of the pelvis and pelvic sidewall is
      necessary before a gynaecologist can even contemplate making an initial
      examination and start management in cases of pelvic pathology or malignancy. This
      chapter provides basic information on gross pelvic anatomy structures that are of
      clinical relevance and discusses their correlation with medical imaging,
      especially magnetic resonance imaging (MRI). MRI is an ideal non-invasive
      technique in the assessment of normal anatomy and tissue characterization of
      pelvic pathology. The excellent soft-tissue contrast and the ability to direct
      multiplanar imaging and to demonstrate blood vessels without the use of
      intravenous contrast make MRI superior to other imaging modalities in the
      evaluation of pelvic abnormalities. The anatomical relation of the visceral
      organs, the differential zonal anatomy of the corpus uteri and the cyclical
      endometrial changes during the menstrual cycle are well depicted with MRI.

PMID- 16275094
TI  - Gynaecological cancer surgery.
AB  - Cancers of the female genital tract account for a significant proportion of
      cancers in women. Surgery plays a major role in the management of these patients.
      As a single modality, it provides definitive treatment for early-stage cancers
      and contributes to the management of patients with advanced cancers as part of
      multimodality treatment. Surgery can involve relatively simple procedures, such
      as wide local excision for microinvasive lesions of the vulva. However, for more
      advanced cancers, such as metastatic ovarian cancer, surgery can be very complex
      indeed, at times requiring resection of non-gynaecological organs, such as small
      or large bowel. Extensive surgical training and experience is needed to
      successfully manage patients with these challenging conditions, and this has
      resulted in the development of the subspecialty of gynaecological oncology. This
      chapter discusses the place of surgery in the treatment of individual
      gynaecological cancers.

PMID- 16275095
TI  - Hysterectomy.
AB  - Hysterectomy is one of the most commonly performed major surgical procedures;
      approximately 100,000 are performed in the UK each year. Hysterectomy can be
      total or subtotal. The postulated benefits of subtotal hysterectomy--better
      pelvic floor and sexual function--have not been confirmed in randomised trials.
      Traditionally, hysterectomy was performed using either an abdominal or vaginal
      approach. More recently, laparoscopic techniques have been used. The decision
      about the technique used is often related to the surgeon's training and
      expertise, as the indications for each technique overlap. Vaginal hysterectomy is
      probably the preferred route because it is quicker and cheaper than laparoscopic
      hysterectomy, with no other clear differences in outcome measures. Laparoscopic
      hysterectomy has a number of advantages over abdominal hysterectomy:
      specifically, shorter hospital stay and quicker return to normal activities;
      complication rates, however, appear to be greater. This also seems to be the case
      with radical hysterectomy performed for cervical cancer.

PMID- 16275096
TI  - Perioperative patient management.
AB  - Modern perioperative care is complex and involves a large number of staff from
      multiple disciplines. Patient outcomes depend on well-designed processes,
      consistent clinical practice, and effective communication. Perioperative care
      should be a unified process of multiple coordinated steps. There should be a
      hospital-based multidisciplinary service to manage and plan this process. Early
      assessment of the patient's comorbidities is essential to plan patient
      preparation. Ideally, patients should be fully prepared before the day of
      surgery, and only admitted to hospital shortly before surgery. For many common
      clinical challenges, there is a range of accepted management regimes.
      Institutionally consistent clinical practice is necessary to optimise patient
      outcome. Postoperative management should be based on standardised observations
      and care protocols, prevention strategies targeted at common problems, and rapid
      response by high-level teams to early physiological signs of complications.

PMID- 16275097
TI  - Dental occlusion and body posture: no detectable correlation.
AB  - The present study was designed to determine if a correlation could be found
      between dental occlusion and body posture through posturography. Twenty-six
      healthy subjects (mean age 26.8+/-5.3 years) were monitored under opposing visual
      (eyes open/closed) and dental occlusion (mandibular rest/intercuspidation
      positions) conditions. The spatial (absolute displacement of centre of pressure
      from the theoretical point; ACOPD) and dynamic (sway area, length and velocity)
      posturographic parameters were recorded. Statistically significant differences
      were found among the experimental conditions for all of the variables except for
      ACOPD. Dynamic posturographic parameters were higher for eyes closed versus eyes
      open under both mandibular positions, although there were no differences between
      mandibular rest position and dental intercuspidation under the different visual
      conditions. This study thus shows no detectable correlation at the posturography
      level between dental occlusion and body posture.

PMID- 16275098
TI  - Hypersensitivity and loss of disease site targeting caused by antibody responses
      to PEGylated liposomes.
AB  - The systemic application of nucleic acid drugs requires delivery systems that
      overcome the poor pharmacokinetics, limited biodistribution, and inefficient
      uptake of nucleic acids. PEGylated liposomes show considerable promise because of
      their intrinsic ability to accumulate at disease sites and facilitate
      transfection of target cells. Unlike many viral vectors, PEGylated liposomes are
      generally considered to be nonimmunogenic. We have developed a PEGylated liposome
      for the systemic administration of plasmid DNA that achieves high levels of
      selective gene expression at distal tumor sites. Here we report that the in vivo
      efficacy and safety of these systems can be severely compromised following repeat
      administration. This phenomenon is characterized by a loss of disease site
      targeting, accelerated clearance from the blood, and acute hypersensitivity.
      These effects are fully attributable to a surprisingly robust, long-lived
      antibody response generated against polyethylene glycol (PEG) that results from
      the strong adjuvant effect of the plasmid payload. Importantly, immunogenicity
      may be substantially reduced by modifying the alkyl chain of the PEG-lipid
      conjugate, thereby allowing successful repeat dosing of the modified plasmid
      formulations without adverse side effects. Immunogenicity is a relevant concern
      for a number of nonviral delivery systems given the potent immunostimulatory
      properties of many nucleic acid drugs.

PMID- 16275099
TI  - Exosomes derived from genetically modified DC expressing FasL are anti
      inflammatory and immunosuppressive.
AB  - We previously have demonstrated the ability of primary murine bone marrow-derived
      DC (BM-DC), genetically modified by adenoviral infection to express FasL, to
      inhibit progression of established collagen-induced arthritis (CIA) following
      systemic delivery. Here we demonstrate that exosomes derived from genetically
      modified BM-DC expressing FasL are able to inhibit inflammation in a murine
      footpad model of delayed-type hypersensitivity (DTH). Local administration of
      exosomes derived from DC expressing FasL (Exo/FasL) as well as the parental
      DC/FasL resulted in a significant reduction in swelling in both the treated and
      the untreated distal paw. However, both the DC/FasL and the Exo/FasL were unable
      to suppress the DTH response in lpr (Fas-deficient) mice. Gene transfer of FasL
      to BM-DC from gld (FasL-deficient) mice resulted in restoration of the ability of
      DC as well as DC-derived exosomes to suppress DTH. The ability of DC-derived
      exosomes and DC to suppress DTH responses was antigen specific and MHC class II
      dependent, but class I independent. The injected exosomes were found to be
      internalized into CD11c(+) cells at the site of injection and in the draining
      popliteal lymph node. Systemic injection of exosome/FasL into mice with
      established CIA resulted in significant disease amelioration. These results
      demonstrate that both systemic and local administration of exosomes derived from
      FasL-expressing DC are able to suppress antigen-specific immune responses through
      an MHC class II-dependent pathway, resulting in effective and sustained treatment
      of established collagen-induced arthritis and suppression of the DTH inflammatory
      response. These results suggest that DC/FasL-derived exosomes could be used
      clinically for the treatment of inflammatory and autoimmune diseases.

PMID- 16275100
TI  - A stainless steel sheath for endoscopic surgery and its application in surgical
      evacuation of putaminal haemorrhage.
AB  - A stainless steel tube was used as an endoscope sheath in combination with a
      working channel endoscope to evacuate hypertensive putaminal intracerebral
      haematoma (ICH). A frontal entry point ipsilateral to the haematoma was selected
      for insertion of the sheath. From January to June 2004, seven patients with
      putaminal ICH underwent endoscopic surgery in our hospital. There were no
      surgical complications. Haematoma evacuation rates were greater than 90% (median
      of 93%). Six patients (87%) regained consciousness within one week. Six patients,
      including four who had no residual disability and two who had moderate
      disability, were able to function independently. One patient remained in a
      persistent vegetative state at clinical follow-up after 6 months. Use of a
      stainless steel endoscopic sheath combined with working channel endoscopy via a
      frontal approach facilitates evacuation of putaminal ICH.

PMID- 16275101
TI  - Platypnoea-orthodeoxia syndrome in association with an ascending aortic aneurysm.
AB  - Platypnoea-orthodeoxia syndrome is a uncommon condition presenting with dyspnoea
      and cyanosis that are characteristically worse in the upright posture and
      improved by lying supine. We present the case of a patient with a thoracic aortic
      aneurysm and a patent foramen ovale who presented with platypnoea-orthodeoxia
      syndrome. Diagnosis was established using transoesophageal echocardiography. We
      suggest a mechanism for the development of dyspnoea and hypoxia in patients with
      this disorder.

PMID- 16275102
TI  - Methemoglobinemia revisited: an important complication after transesophageal
      echocardiography.
AB  - Methemoglobinemia induced by the use of benzocaine-containing topical anesthetics
      is a rare, but potentially lethal complication after transesophageal
      echocardiography (TEE). We report a patient who developed methemoglobinemia after
      TEE. A review of the literature was performed and the majority of cases of
      benzocaine-induced methemoglobinemia reported thus far have occurred in patients
      undergoing TEE, endotracheal intubation, esophagogastroduodenoscopy, and
      bronchoscopy. All of these procedures have become more frequent than before, and
      there is a need to reemphasize the potential problem and to reconsider the need
      for further use of topical anesthetics.

PMID- 16275103
TI  - A combined approach of docking and 3D QSAR study of beta-ketoacyl-acyl carrier
      protein synthase III (FabH) inhibitors.
AB  - The enzyme FabH catalyzes the initial step of fatty acid biosynthesis via a type
      II fatty acid synthase. The pivotal role of this essential enzyme combined with
      its unique structural features and ubiquitous occurrence in bacteria has made it
      an attractive new target for the development of antibacterial and antiparasitic
      compounds. Three-dimensional quantitative structure-activity relationship (3D
      QSAR) studies such as comparative molecular field analysis (CoMFA) and
      comparative molecular similarity indices analysis (CoMSIA) and docking
      simulations were conducted on a series of potent benzoylaminobenzoic acids.
      Docking studies were employed to position the inhibitors into the FabH active
      site to determine the probable binding conformation. A reasonable correlation
      between the predicated binding free energy and the inhibitory activity was found.
      CoMFA and CoMSIA were performed based on the docking conformations, giving q(2)
      of 0.637 and 0.697 for CoMFA and CoMSIA models, respectively. The predictive
      ability of the models was validated using a set of compounds that were not
      included in the training set and progressive scrambling test. Mapping the 3D QSAR
      models to the active site of FabH related that some important amino acid residues
      are responsible for protein-inhibitor interaction. These results should be
      applicable to the prediction of the activities of new FabH inhibitors, as well as
      providing structural understanding.

PMID- 16275104
TI  - Modelling, synthesis and biological evaluation of novel glucuronide-based probes
      of Vibrio cholerae sialidase.
AB  - The development of sialidase inhibitors is an area of continuing interest due to
      their potential use as therapeutic agents to combat viral and bacterial
      infections. Herein, we report our studies involving the sialidase from the
      pathogen Vibrio cholerae, through the modelling, synthesis and biological
      evaluation of mimetics of 5-acetamido-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto
      non-2-enonic acid (Neu5Ac2en, 1), a naturally occurring sialidase inhibitor.
      These mimetics are O- and S-glycosides of N-acetyl-D-glucosaminuronic acid in
      which the aglycone portion effectively replaces the C-6 glycerol side chain of
      Neu5Ac2en (1). The choice of aglycones was aided by use of the X-ray crystal
      structure of V. cholerae sialidase complexed with Neu5Ac2en (1). All Neu5Ac2en
      mimetics tested were found to inhibit V. cholerae sialidase as determined using a
      standard fluorometric assay.

PMID- 16275105
TI  - 3D QSAR study of hypolipidemic asarones by comparative molecular surface
      analysis.
AB  - Three-dimensional quantitative structure-activity relationship (3D QSAR) modeled
      for alpha-asarone derivatives using the comparative molecular surface analysis
      (CoMSA) allowed us to reveal a correlation between the activity of these
      compounds and the electrostatic potential at the molecular surface. The grid
      formalism (s-CoMSA) allowed us to indicate a pharmacophore that is of key
      importance for compound activity. The CoMSA formalism coupled with the iterative
      variable elimination method gives a highly predictive model.

PMID- 16275106
TI  - Human serum albumin interaction with formononetin studied using fluorescence
      anisotropy, FT-IR spectroscopy, and molecular modeling methods.
AB  - Interaction of formononetin with a model transport protein, human serum albumin
      (HSA), has been studied using fluorescence anisotropy, FT-IR spectroscopy, and
      molecular modeling methods. Upon binding with HSA, the fluorescence spectrum of
      formononetin exhibits appreciable hypsochromic shift along with an enhancement in
      the fluorescence intensity. Gradual addition of HSA led to a marked increase in
      fluorescence anisotropy (r). From the value of fluorescence anisotropy, it is
      argued that the drug is located in a restricted environment of protein. The
      binding constant (K approximately 1.6 x 10(5) M(-1)) and the standard free energy
      change (DeltaG(0) approximately -29.9 kJ/mol) of formononetin-HSA interaction
      have been calculated according to the relevant fluorescence data. Fourier
      transform infrared measurements have shown that the secondary structures of the
      protein have been changed by the interaction of formononetin with HSA.
      Computational mapping of the possible binding sites of formononetin revealed the
      molecule to be bound in the large hydrophobic cavity of subdomain IIA.

PMID- 16275107
TI  - Epoxide opening in water and screening in situ for rapid discovery of enzyme
      inhibitors in microtiter plates.
AB  - A method utilizing the strategy of epoxide opening by amine with water as co
      solvent and screening in situ was developed for rapid discovery of protein
      inhibitors. Using this approach, HIV protease inhibitors with novel P1' residues
      were identified in our study. This strategy should be applicable for the
      efficient assembly of diverse compound collections for inhibitors' discovery and
      optimization in other systems.

PMID- 16275108
TI  - QSAR studies of N(1)-(5-chloro-2-pyridyl)-2-{[4-(alkyl methyl)benzoyl]amino}-5
      chlorobenzamide analogs.
AB  - Factor X(a) has materialized as a key enzyme for the intervention of blood
      coagulation cascade and for the development of new antithrombotic agents. It is
      the lone enzyme that is responsible for the production of thrombin and is
      therefore an attractive target for the control of thrombus formation. The
      biological activities (log1/IC(50)) of anthranilamide-based factor X(a)
      inhibitors were quantitatively analyzed in terms of physicochemical parameters by
      the regression analysis. Structural requirements for maximal potency were derived
      from the results of a quantitative structure activity relationship analysis. The
      leave-one-out cross-validation method was used to judge the predictive power of
      final equations.

PMID- 16275109
TI  - Design of potent inhibitors for Schistosoma japonica glutathione S-transferase.
AB  - We implemented both structure-based drug design and the concept of polyvalency to
      discover a series of potent and unsymmetrical Schistosoma japonicum glutathione S
      transferase (SjGST) inhibitors 10-12. This strategy achieved not only an
      excellent enhancement (10- to 490-fold) in the inhibitory potency, compared to
      the monofunctional analogues 1-5, but was also an effective modification by
      selecting a hydrophobic moiety with a flexible linker. The designed compounds
      with a low micromolar hit demonstrate special values in refining the new
      generation of SjGST inhibitors. The stoichiometry of the binding is one inhibitor
      molecule per SjGST monomer via isothermal titration calorimetric measurement.

PMID- 16275110
TI  - An evaluation of the quality of epilepsy education on the Canadian World Wide
      Web.
AB  - BACKGROUND: Despite the substantial amount of epilepsy-related information
      available on the Internet, little is known about its quality. Epilepsy-related
      information in English on the Canadian Internet was reviewed. METHODS: Popular
      search engines (google.ca, yahoo.ca, ca.altavista.com, simpatico.msn.ca) were
      interrogated. Web sites aimed primarily at patient and family education, geared
      toward human epilepsy, and epilepsy in general as opposed to one specific type or
      aspect of epilepsy, were included. Web sites were then subdivided in to
      proprietary (directly sponsored by the industry) and nonproprietary, and
      evaluated according to compliance with the principles of the Health on the Net
      (HON) Foundation Code of Conduct. Web sites without comprehensive contents were
      excluded. Comparison between total scores was done using the rank test.
      Categorized descriptors were assessed with t tests. RESULTS: Five proprietary and
      fourteen nonproprietary websites were identified. None of them were compliant
      with all eight principles of the HON code. The average number of principles with
      which these sites were in compliance was 3.3 (range: 1-6.5, P = 0.4, proprietary
      vs nonproprietary). CONCLUSIONS: The Internet has the potential to be a very
      powerful educational tool for patients with epilepsy. However, most of the easily
      accessed epilepsy web sites do not comply with accepted standards for health web
      sites.

PMID- 16275111
TI  - Attitudes and practices of families and health care personnel toward children
      with epilepsy in Kilifi, Kenya.
AB  - PURPOSE: Epilepsy is common in underresourced countries, where most people with
      epilepsy do not take antiepileptic drugs (AEDs). This underutilization, referred
      to as the treatment gap, was investigated in Kilifi, Kenya, by exploring the
      sociocultural context in which children with epilepsy and their families live.
      This study focused particularly on what effect attitudes and practices might have
      on service utilization, particularly the use of AEDs. METHODS: Attitudes and
      practices toward children with epilepsy were examined using qualitative data
      collection methods, namely, interviews, focus group discussions, group
      activities, and observations. These were carried out with children diagnosed as
      having active epilepsy, their parents, their grandparents, and health care
      personnel. RESULTS: The responses illustrate both positive and negative
      attitudes, underpinning a wide variety of practices toward children with
      epilepsy. They also indicate the use of several types of services that vary
      between the traditional, medical, educational, and religious. The choice of these
      services was affected by different socioeconomic factors, the complex
      interrelationship of which offers some explanation for the underutilization of
      AEDs. CONCLUSIONS: The treatment gap may be explained by a "health versus
      sickness" model, accounting for families' health-seeking behavior in relation to
      their perception of cause and treatment. In this model, occasional convulsions
      associated with fever in younger children are placed in the "health sphere,"
      making recommendations of regular and continued medication illogical for what is
      perceived to be a healthy child. When seizures persist beyond a certain age, the
      child is placed in the "sickness sphere," meaning that the child is incurable and
      treatment attempts are futile. Better levels of understanding and information
      sharing among children with epilepsy, their families, and health care personnel
      are required to improve use of medical services. Possible interventions include
      community-based services and health education programs for the community and
      service providers.

PMID- 16275112
TI  - Delayed visceral malperfusion in aortic dissection-successful surgical
      revascularization using a saphenous vein graft.
AB  - Obstruction of the thoracoabdominal aorta and/or its branches with subsequent
      organ ischemia is a frequent complication of aortic dissection. Surgical and
      percutaneous fenestrations have been used and endovascular stenting has emerged
      as an additional less invasive approach. In some cases, surgical
      revascularization may be the most successful procedure. We report two patients
      who underwent surgical revascularization of the celiac trunk and superior
      mesenteric artery for delayed abdominal malperfusion due to aortic dissection.

PMID- 16275113
TI  - Limited role of aortic size in the genesis of acute type A aortic dissection.
AB  - OBJECTIVE: Increased dimension of the aortic root and proximal aorta is
      considered a significant risk factor for catastrophic events that involve the
      ascending aorta. The objective of this study was to determine the possible
      correlation between pre-dissection aortic diameter and the occurrence of Stanford
      type A aortic dissection. METHODS: Samples of dissected ascending aortas were
      obtained from 220 patients at the time of their operation. Two groups were
      identified: patients with connective tissue disorders (Group 1, n=94) and those
      without (Group 2, n=126). Measurements of the true (intimal) lumen were conducted
      and extrapolated as reliable approximation of pre-dissection aortic diameter. The
      possible association of intimal diameter with anthropometric and demographic data
      was analyzed. RESULTS: Median aortic diameter was, respectively, 41.8 and 41.3mm
      for patients with and without connective tissue disorders (41.4mm for the entire
      cohort). Data analysis indicated that 57% of patients had aortic diameter above
      40 mm, while patients with frank aneurysm accounted only for 10%; this proportion
      was higher in Group 1 compared to Group 2 (17.2% vs 4.7%). Poor or no correlation
      was demonstrated between aortic size and any of the anthropometric or demographic
      variables assayed. Significant subgroup differences were found among patients
      with a history of cigarette smoking, hypertension, diabetes, chronic renal
      insufficiency, and bicuspid aortic valve. CONCLUSION: Although aortic diameter
      remains a strong indication for preventive surgery in patients with inherited
      connective tissue disorders, acute aortic dissection occurs rarely in the setting
      of true ascending aortic aneurysms, and despite normal or near-normal aortic size
      in more than one-third of subjects. Dissection superimposing on small aortic
      diameters can be regarded as an expression of substantial functional tissue
      susceptibility to aortic catastrophic events.

PMID- 16275115
TI  - Adventitial inversion technique without the aid of biologic glue or Teflon
      buttress for acute type A aortic dissection.
AB  - OBJECTIVE: This study was performed to evaluate the clinical usefulness of the
      adventitial inversion technique in acute type A aortic dissection, with special
      attention to the impact of this procedure on the postoperative status of false
      lumen evaluated by computed tomographic scan. METHODS: From March 2001 to
      November 2004, 18 consecutive patients underwent emergent surgery for acute type
      A aortic dissection. Supracoronary graft replacement was performed in all the
      patients (ascending aorta/hemiarch replacement: 13/18=72%, total arch
      replacement: 5/18=28%). The adventitial inversion technique was used for both the
      proximal and the distal stump constructions of the dissected aortic wall without
      the aid of Teflon felt or biologic glue. Aortic regurgitation was treated with
      resuspension of the aortic commissures. RESULTS: There were two hospital deaths
      and the overall hospital mortality rate was 11.1%. The mean postoperative blood
      loss was 635+/-214 ml and no reexploration was required in any of the patients.
      Postoperative computed tomography showed closure of the false lumen in aortic
      root, aortic arch, and proximal descending thoracic aorta in all of the surviving
      patients. Postoperative echocardiography demonstrated no aortic regurgitation in
      any of the patients. Two patients died late postoperatively from unrelated causes
      to aortic dissection. The remaining 14 patients are doing well without a second
      stage operation for aortic root or distal aortic lesions during the follow-up
      period of 7-51 months (mean: 28+/-14 months). CONCLUSIONS: The adventitial
      inversion technique provides an excellent immediate hemostasis and facilitates
      thrombotic closure of the proximal and the distal false lumen in the treatment
      for acute type A aortic dissection.

PMID- 16275116
TI  - Suppression of ICAM-1 in human venous endothelial cells by small interfering
      RNAs.
AB  - OBJECTIVE: Cardiopulmonary bypass-mediated release of proinflammatory cytokines
      promotes the transendothelial migration of leukocytes. Among others,
      intercellular adhesion molecule (ICAM) is essential for this migratory process
      within the venous bypass graft, which finally contributes to a diminished early
      patency rate by thickening of the intima. Small interfering ribonucleic acids
      (siRNAs) are efficient and specific modulators of endogenous gene expression.
      This study describes the application of siRNAs to suppress ICAM-1 expression on
      the surface of human venous endothelial cells. METHODS: Primary cultures of human
      venous endothelial cells were either transfected with ICAM-1 siRNA, with a
      scrambled control siRNA or cultured without transfection. ICAM-1 expression was
      analyzed with or without TNF-alpha stimulation by flow cytometry. RESULTS: Upon
      TNF-alpha stimulation, cells transfected with ICAM-1 siRNA showed a six- to seven
      fold decreased ICAM-1 expression compared to untransfected cells or cells
      transfected with the scrambled control siRNA. CONCLUSIONS: This is the first
      report that ICAM-1 expression can be effectively silenced by siRNAs on
      endothelial cells from human saphenous veins. This new technology may render
      novel therapeutic concepts to reduce early graft failure by protecting venous
      bypass grafts against early intra- or postoperative leukocyte infiltration.

PMID- 16275117
TI  - Effects of pre-natal and early post-natal undernutrition on adult internal
      thoracic artery function.
AB  - OBJECTIVE: Previous studies in humans and animals have suggested that
      undernutrition in utero and in early post-natal life may lead to altered vascular
      function in a number of peripheral arteries. We investigated the effect of pre-
      and post-natal nutrient restriction on the vascular reactivity of the left
      internal thoracic artery using a sheep model. METHODS: Welsh mountain ewes were
      mated and assigned to three dietary groups: (1) 100% of total nutritional
      requirements (control, n=6); (2) 50% of total nutritional requirements during the
      first 31 days of gestation (n=6); and (3) 50% nutritional restriction during the
      first 31 days of gestation, followed by a restriction in the diet of their
      offspring 12-25 weeks post-natally, designed to produce a 15% reduction in growth
      trajectory (n=7). The male offspring were sacrificed at 130 weeks; the left
      internal thoracic artery was mounted onto a wire myograph and the reactivity of
      the vessel to various agonists measured. RESULTS: The offspring of animals who
      underwent an early gestation nutrient restriction had a significantly increased
      basal tone (0.41+/-0.25 vs 6.34+/-1.35, p=0.015) and sensitivity to phenylephrine
      (log EC(50): -6.23+/-0.04 M vs -5.74+/-0.17 M, p=0.036) as compared with control
      animals. However, this phenomenon was not seen in animals that underwent both pre
      and post-natal nutrient restriction. CONCLUSIONS: Pre-natal undernutrition
      increases the basal tone and sensitivity of the left internal thoracic artery to
      phenylephrine. This effect is significantly attenuated by continued
      undernutrition in early post-natal life. These experiments suggest that in utero
      and early post-natal undernutrition may be important determinants of graft
      function in later life.

PMID- 16275118
TI  - Plasminogen activators: a comparison.
AB  - Thrombolytic drugs play a crucial role in the management of patients with acute
      myocardial infarction, pulmonary embolism, deep vein thrombosis, arterial
      thrombosis, acute thrombosis of retinal vessel, extensive coronary emboli, and
      peripheral vascular thromboembolism. Recognition of the importance of
      fibrinolytic system in thrombus resolution has resulted in the development of
      different fibrinolytic agents. Now a days several newer plasminogen activators
      with different pharmacokinetic and pharmacodynamic properties have been developed
      to treat thrombotic disease, which are fibrin specific with prolonged half-life
      and can be administered as a single bolus.

PMID- 16275119
TI  - Genetic analysis of adrenal absence: agenesis and aplasia.
AB  - The adrenal cortex shares a common embryological heritage with the gonad and
      kidney: all are derived from components of the urogenital ridge. Adrenocortical
      specification from this embryonic structure and the ultimate organogenesis of the
      adrenal gland are directed by the sequential expression of transcriptional
      regulators, with later development being additionally mediated by endocrine
      hormones that regulate organ maintenance and tissue differentiation. Recent
      advancements in the field of human and mouse genetics have accumulated evidence
      for a host of novel factors involved in these processes, such as the hedgehog
      signaling network and peptides derived from proopiomelanocortin.

PMID- 16275120
TI  - Genetic polymorphisms and multifactorial diseases: facts and fallacies revealed
      by the glucocorticoid receptor gene.
AB  - In recent years enormous progress in determining the sequence of the human genome
      has led to a rapid development of research into polymorphisms in genes involved
      in complex diseases. It is clear, however, that there are important limitations
      in many of these association studies. Problems with reliable and reproducible
      phenotyping, the number of individuals studied, racial heterogeneity, population
      stratification (founder effect), functionality and multiple testing often mean
      that studies are not reproducible. In this review we describe a number of the
      limitations related to this type of research; from both our own experience with
      studies on polymorphisms in the glucocorticoid receptor gene, and shortcomings
      and solutions from the literature.

PMID- 16275121
TI  - Transcriptional corepression by SHP: molecular mechanisms and physiological
      consequences.
AB  - Small heterodimer partner (SHP; NR0B2), an exceptional member of the mammalian
      nuclear receptor family, directly modulates the activities of conventional
      nuclear receptors by acting as an inducible and tissue-specific corepressor.
      Recent progress in dissecting underlying molecular mechanisms, identifying target
      factors and target genes, and uncovering physiological functions points to the
      regulatory involvement of SHP in diverse metabolic and intracellular pathways
      that awaits future clarification. In this review, we carry out a comprehensive
      survey of all published data and discuss our current understanding of molecular
      mechanisms and physiological consequences governing SHP action.

PMID- 16275122
TI  - Expression of Panza, an alpha2-macroglobulin, in a restricted dorsal domain of
      the primitive gut in Xenopus laevis.
AB  - Alpha2-macroglobulin is a major serum protein with diverse functions, including
      inhibition of protease activity and binding of growth factors, cytokines, and
      disease factors. We have cloned and characterized Panza, a new Xenopus laevis
      alpha2-macroglobulin. Panza has 56-60% amino acid similarity with previously
      identified Xenopus, mouse, rat and human alpha2-macroglobulins, indicating that
      Panza is a new member of the alpha2-macroglobulin family. Panza mRNA is first
      detected at the beginning of neurulation in the dorsal endoderm lining the
      primitive gut (archenteron roof). At the completion of neurulation and continuing
      through the late tadpole stage, Panza is restricted to a dorsal domain of the gut
      endoderm adjacent to the notochord and extending along the entire anterior
      posterior axis. With outgrowth of the tailbud, Panza expression persists in the
      chordaneural hinge at the posterior end of the differentiating notochord and
      extends into the floor plate of the posterior neural tube. As gut coiling
      commences, Panza expression is initiated in the liver, and the dorsal domain of
      Panza expression becomes limited to the midgut and hindgut. With further gut
      coiling, strong Panza expression persists in the liver, but is lost from other
      regions of the gut. The expression of Panza in endodermal cells adjacent to the
      notochord points to a potential role for Panza in signal modulation and/or
      morphogenesis of the primitive gut.

PMID- 16275124
TI  - Role of adjunct pharmacologic therapy in the era of drug-eluting stents.
AB  - The success of percutaneous coronary intervention (PCI) has historically been
      limited by a relatively high rate of restenosis, a response of the coronary
      artery to trauma induced during PCI. Bare-metal stents, by providing a supportive
      intravascular scaffolding, have significantly reduced the incidence of restenosis
      compared with traditional balloon PCI. However, significant loss of lumen within
      the bare-metal device (in-stent restenosis) occurs in 10-30% of patients within 6
      months of the procedure. The recent introduction of drug-eluting stents,
      permitting local delivery of high concentrations of immunosuppressive or anti
      proliferative agents, promises to prevent the processes underlying restenosis.
      Although these devices have been successful in providing an incremental reduction
      in rates of restenosis, they are expensive. To date, clinical trials of
      pharmacologic treatment have failed to demonstrate a clinically significant
      impact on restenosis. Recently, results of the Cilostazol for Restenosis (CREST)
      trial, a randomized, double-blind study, show that cilostazol reduces the risk of
      restenosis in patients who receive bare-metal stents, including high-risk
      patients. Effective adjunct pharmacologic therapy to prevent in-stent restenosis,
      therefore, remains desirable, particularly in patients receiving bare-metal
      stents, and potentially in patients receiving drug-eluting stents who are at high
      risk for restenosis (i.e., those with diabetes, long lesions, and small vessels).

PMID- 16275123
TI  - Effect of silymarin and its polyphenolic fraction on cholesterol absorption in
      rats.
AB  - This study evaluated the influence of silymarin (SM) and polyphenolic fraction
      (PF) of silymarin on cholesterol absorption in rats fed on high cholesterol diet
      (HCD). HCD induced a remarkable increase in hepatic, plasma, VLDL and LDL
      cholesterol, a decrease in HDL cholesterol and an elevation in triacylglycerol
      (TAG) levels in plasma, VLDL and in the liver. SM and PF were administered as
      dietary supplements (1.0%) in HCD for 18 days. Intestinal cholesterol absorption
      was measured by dual-isotope plasma ratio method, which calculates percent of
      cholesterol absorption from the ratio of two labelled cholesterol doses, one
      given intragastrically (14C) and one intravenously (3H). Silymarin and PF
      significantly reduced cholesterol absorption in rats fed on HCD and caused
      significant decreases in plasma and VLDL cholesterol and content of cholesterol
      and TAG in the liver. The level of HDL cholesterol was significantly increased
      after silymarin, but not after administration of PF. The levels of TAG in plasma
      and VLDL were not affected by either silymarin or PF. These results suggest that
      the inhibition of cholesterol absorption caused by silymarin and its polyphenolic
      fraction could be a mechanism contributing to the positive changes in plasma
      cholesterol lipoprotein profile and in lipid content in liver.

PMID- 16275125
TI  - Cilostazol in secondary prevention of stroke: impact of the Cilostazol Stroke
      Prevention Study.
AB  - According to recent epidemiological data in Japan, stroke affects roughly 5.3
      males and 3.9 females per 1000 person-years and is the third leading cause of
      mortality. At present, management strategies for secondary prevention of stroke
      include aggressive treatment of cardiovascular risk factors (i.e., hypertension,
      smoking cessation, etc.). Antiplatelet drugs in Japan, namely aspirin and
      cilostazol, are utilized regularly for the prevention of secondary stroke. While
      aspirin is beneficial for a wide range of cardiovascular endpoints, including
      total and ischemic strokes, it is also associated with significantly increased
      risks for hemorrhagic infarction. Cilostazol, by contrast, has been shown to
      significantly reduce the risk of recurrent strokes without affecting the
      occurrence of intracranial hemorrhage. In the Cilostazol Stroke Prevention Study,
      a randomized double-blind, placebo-controlled trial involving more than 1000
      Japanese patients, cilostazol was found to reduce the risk of secondary stroke by
      41.7% compared with placebo, a statistically significant reduction (P = 0.015).
      The greatest risk reduction (43.4% in cilostazol versus placebo, P = 0.0373) was
      found in patients who initially had a lacunar infarction, suggesting that
      cilostazol has a specific effect against small-vessel disease. In addition,
      cilostazol achieved significant risk reductions on a number of combined endpoints
      (e.g., cerebral infarction, intracranial hemorrhage, myocardial infarction, or
      vascular death), and was associated with benefits in intent-to-treat analyses.
      These findings indicate that cilostazol may have a role as a vascular
      neuroprotectant, but the clinical implications are limited by the fact that
      patients were randomized to placebo instead of aspirin, which is the standard of
      care.

PMID- 16275126
TI  - Imaging dynamic interactions in immune responses.

PMID- 16275127
TI  - Hybrid joint formation in human V(D)J recombination requires nonhomologous DNA
      end joining.
AB  - In V(D)J recombination, the RAG proteins bind at a pair of signal sequences
      adjacent to the V, D, or J coding regions and cleave the DNA, resulting in two
      signal ends and two hairpinned coding ends. The two coding ends are joined to
      form a coding joint, and the two signal ends are joined to form a signal joint;
      this joining is done by the nonhomologous DNA end joining (NHEJ) pathway. A
      recombinational alternative in which a signal end is recombined with a coding end
      can also occur in a small percentage of the V(D)J recombination events in murine
      and human cells, and these are called hybrids (or hybrid joints). Two mechanisms
      have been proposed for the formation of these hybrids. One mechanism is via NHEJ,
      after initial cutting by RAGs. The second mechanism does not rely on NHEJ, but
      rather invokes that the RAGs can catalyze joining of the signal to the hairpinned
      coding end, by using the 3'OH of the signal end as a nucleophile to attack the
      phosphodiester bonds of the hairpinned coding end. In the present study, we
      addressed the question of which type of hybrid joining occurs in a physiological
      environment, where standard V(D)J recombination presumably occurs and normal RAG
      proteins are endogenously expressed. We find that all hybrids in vivo require DNA
      ligase IV in human cells, which is the final component of the NHEJ pathway.
      Hence, hybrid joints rely on NHEJ rather than on the RAG complex for joining.

PMID- 16275128
TI  - Cloning, expression, and characterization of a xylanase 10 from Aspergillus
      terreus (BCC129) in Pichia pastoris.
AB  - A full-length xylanase gene, encoding 326 amino acids belonging to the fungal
      glycosyl hydrolase family 10, from Aspergillus terreus BCC129 was cloned and
      sequenced. Sequence analysis suggested that the first 25 amino acids of this
      enzyme is the signal peptide. Therefore, only the mature xylanase gene of 906 bp
      was cloned into a yeast expression vector, pPICZalphaA, for heterologous
      expression in Pichia pastoris. A band of approximately, 33 kDa was observed on
      the SDS-PAGE gel after one day of methanol induction. The expressed enzyme was
      purified by gel filtration chromatography. The purified recombinant xylanase
      demonstrated optimal activity at 60 degrees C, pH 5.0 and a Km of 4.8 +/- 0.07
      mg/ml and a Vmax of 757 +/- 14.54 micromol/min mg, using birchwood xylan as a
      substrate. Additionally, the purified enzyme demonstrated broad pH stability from
      4 to 10 when incubated at 40 degrees C for 4 h. It also showed a moderate thermal
      stability since it retained 90% of its activity when incubated at 50 degrees C,
      30 min, making this enzyme a potential use in the animal feed and paper and pulp
      industries.

PMID- 16275129
TI  - Synthesis and assembly of an adjuvanted Porphyromonas gingivalis fimbrial antigen
      fusion protein in plants.
AB  - The gram-negative anaerobic oral bacterium Porphyromonas gingivalis initiates
      periodontal disease by binding to saliva-coated oral surfaces. To assess whether
      edible plants can synthesize biologically active P. gingivalis fimbrial antigen,
      for application as an oral vaccine, a cDNA fragment encoding the C-terminal
      binding portion of P. gingivalis fimbrial protein (FimA), was cloned into a plant
      expression vector immediately downstream of a cDNA fragment encoding the cholera
      toxin B subunit (CTB). The chimeric plasmid was transferred into potato (Solanum
      tuberosum) cells and the ctb-fimA cDNA fragment detected in transformed leaf
      genomic DNA by PCR amplification methods. A novel protein band of 21 kDa was
      detected in transformed potato tuber extracts by immunoblot analysis. Oligomeric
      CTB-FimA (266-337) fusion protein was identified in the extracts through the
      binding of anti-CTX and anti-native fimbriae antibodies. The pentameric structure
      of CTB-FimA fusion protein was confirmed by ELISA measurements of GM1 ganglioside
      receptor binding. Quantification of the CTB-FimA fusion protein by ELISA
      indicated that the chimeric protein made up about 0.33% of total soluble tuber
      protein. The biosynthesis of immunologically detectable CTB-FimA fusion proteins
      and the assembly of fusion protein monomers into biologically active pentamers in
      transformed potato tuber tissues demonstrate the feasibility of synthesizing
      adjuvanted fimbrial protein in edible plants for development of adjuvanted
      mucosal vaccines against P. gingivalis generated periodontal disease.

PMID- 16275130
TI  - Cloning, expression, and purification of recombinant bovine rotavirus
      hemagglutinin, VP8*, in Escherichia coli.
AB  - Rotavirus VP8* subunit is the minor trypsin cleavage product of the spike protein
      VP4, which is the major determinant of the viral infectivity and neutralization.
      To study the structure-function relationship of this fragment and to obtain type
      specific reagents, substantial amounts of this protein are needed. Thus, full
      length VP8* cDNA, including the entire trypsin cleavage-encoding region in gene
      4, was synthesized and amplified by RT-PCR from total RNA purified from bovine
      rotavirus strain C486 propagated in MA104 cell culture. The extended VP8* cDNA
      (VP8ext) was cloned into the pGEM-T Easy plasmid and subcloned into the
      Escherichia coli expression plasmid pET28a(+). The correspondent 30 kDa protein
      was overexpressed in E. coli BL21(DE3)pLysS cells under the control of the T7
      promoter. The identity and the antigenicity of VP8ext were confirmed on Western
      blots using anti-His and anti-rotavirus antibodies. Immobilized Ni-ion affinity
      chromatography was used to purify the expressed protein resulting in a yield of 4
      mg of VP8ext per liter of induced E. coli culture. Our results indicate that
      VP8ext maintained its native antigenicity and specificity, providing a good
      source of antigen for the production of P type-specific immune reagents. Detailed
      structural analysis of pure recombinant VP8 subunit should allow a better
      understanding of its role in cell attachment and rotavirus tropism. Application
      of similar procedure to distinct rotavirus P serotypes should provide valuable P
      serotype-specific immune reagents for rotavirus diagnostics and epidemiologic
      surveys.

PMID- 16275131
TI  - Simultaneous determination of myristyl nicotinate, nicotinic acid, and
      nicotinamide in rabbit plasma by liquid chromatography-tandem mass spectrometry
      using methyl ethyl ketone as a deproteinization solvent.
AB  - Myristyl nicotinate (Nia-114) is an ester prodrug being developed for delivery of
      nicotinic acid (NIC) into the skin for prevention of actinic keratosis and its
      progression to skin cancer. To facilitate dermal studies of Nia-114, a novel
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using methyl
      ethyl ketone (MEK) as a deproteinization solvent was developed and validated for
      the simultaneous determination of Nia-114, NIC, and nicotinamide (NAM) in rabbit
      plasma. NAM is the principal metabolite of NIC, which is also expected to have
      chemopreventive properties. The analytes were chromatographically separated using
      a Spherisorb Cyano column under isocratic conditions, and detected by multiple
      reaction monitoring (MRM) in positive-ion electrospray ionization mode with a run
      time of 9 min. The method utilized a plasma sample volume of 0.2 ml and isotope
      labeled D4 forms of each analyte as internal standards. The method was linear
      over the concentration range of 2-1000, 8-1000, and 75-1000 ng/ml, for Nia-114,
      NIC, and NAM, respectively. The intra- and inter-day assay accuracy and precision
      were within +/-15% for all analytes at low, medium, and high quality control
      standard levels. The relatively high value for the lower limit of quantitation
      (LLOQ) of NAM was demonstrated to be due to the high level of endogenous NAM in
      the rabbit plasma (about 350 ng/ml). Endogenous levels of NIC and NAM in human,
      dog, rat, and mouse plasma were also determined, and mean values ranged from <2
      ng/ml NIC and 38.3 ng/ml NAM in human, to 233 ng/ml NIC and 622 ng/ml NAM in
      mouse. Nia-114 was generally unstable in rabbit plasma, as evidenced by loss of
      44-50% at room temperature by 2 h, and loss of 64-70% upon storage at -20 degrees
      C for 1 week, whereas it was stable (<7% loss) upon storage at -80 degrees C for
      1 month.

PMID- 16275132
TI  - Ultra-sensitive determination of Formoterol in human serum by high performance
      liquid chromatography and electrospray tandem mass spectrometry.
AB  - An analytical method was developed and validated to determine Formoterol in human
      serum in the range from 0.40 to 100.24 pg/mL by high performance liquid
      chromatography and tandem mass spectrometry (HPLC-MS/MS) due to the lack of
      efficient methods to determine very low levels of Formoterol in serum and plasma.
      Serum was diluted by water and mixed with the internal standard (d6-Formoterol).
      Formoterol and internal standard were extracted using a cation-exchange solid
      phase column (SCX-3). After eliminating endogenous serum constituents through
      washing steps with water and methanol, elution took place using methanol/ammonia.
      After evaporation of the elution liquid the residue was redissolved and analyzed
      by HPLC-MS/MS with electrospray ionisation (ESI) in positive mode. A gradient
      between 10 mM ammonium formate and acetonitrile was used. The inter-batch
      precision of the calibration standards ranged from 1.55% to 9.01%. The inter
      batch accuracy of the calibration standards ranged from 93.37% to 107.30%. The
      lower limit of quantitation (LLOQ, 0.40 pg/mL) had a precision of 19.67% and an
      accuracy of 96.78%. Comparable results were obtained for quality control samples.
      Stability in human serum was given over three freeze/thaw cycles and 2h at room
      temperature. Formoterol in human serum was stable for at least 6 months below -20
      degrees C. This method has been used widely for quantifying Formoterol after
      inhalation of 9-36 microg of the drug by volunteers. A cross validation with
      human plasma versus serum was performed after this method was successfully
      validated in human serum.

PMID- 16275133
TI  - Period and birth-cohort effects on age of first phencyclidine (PCP) use among
      drug users in New York City, 1960 to 2000.
AB  - PURPOSE: The aim of the study is to determine period and birth-cohort effects in
      the early initiation of phencyclidine (PCP) use in drug users in New York City
      (NYC). METHODS: We analyzed data collected from two surveys of street-recruited
      drug users in NYC. We used survival analysis and proportional hazards modeling to
      assess period and birth-cohort effects on risk for early initiation of PCP use.
      RESULTS: Of 787 participants, 292 (37.1%) had used PCP by the age of 23 years.
      Before 1987, there was a greater risk for initiation of PCP use through the age
      of 23 years (hazard ratio [HR] = 34.77; 95% confidence interval [CI], 21.45
      56.36). Proportional hazards modeling showed that those born in the 1971 to 1975
      birth cohort compared with those born in 1976 to 1980 had a lower risk for
      initiation of PCP use through age 23 years (HR = 0.58; 95% CI, 0.37-0.91). Other
      significant predictors of PCP use by age 23 included white race and having been
      in a juvenile detention center. CONCLUSIONS: There are period and birth-cohort
      differences in the likelihood of early initiation of PCP use. Changes in drug
      culture and social norms may influence the likelihood of initiation of PCP use.
      This may have implications for interventions aimed at slowing the nationwide
      increase in use of PCP.

PMID- 16275134
TI  - Projecting drug use among aging baby boomers in 2020.
AB  - PURPOSE: Greater rates of lifetime drug use among the baby-boom generation,
      combined with the size of that generation, suggest that the number of elderly
      persons using drugs will increase in the next two decades. Given the potential
      public health demands implied by increasing numbers of elderly drug users, the
      goal is to project the numbers of current drug users aged 50 years and older in
      2020. METHODS: Using the modeling and projection methods of Gfroerer et al (2003)
      applied to data from the 1999 to 2001 National Household Surveys on Drug Abuse,
      projections were developed for the use of marijuana, nonmedical use of any
      prescription-type psychotherapeutic drug, and any illicit drug use. RESULTS: From
      1999 to 2001 to 2020, past-year marijuana use in persons 50 years and older is
      forecast to increase from 1.0% to 2.9%. The number of users is expected to
      increase from 719,000 to almost 3.3 million, reflecting the combined effects of
      the increase in rate of use and a projected 51.9% increase in the civilian
      noninstitutionalized population in this age group. Use of any illicit drug will
      increase from 2.2% (1.6 million) to 3.1% (3.5 million), and nonmedical use of
      psychotherapeutic drugs will increase from 1.2% (911,000) to 2.4% (almost 2.7
      million). CONCLUSIONS: These projections call attention to changes to be
      considered in planning and to the need for improved knowledge of the biomedical
      and psychosocial effects of nonmedical drug use on aging and elderly individuals.

PMID- 16275135
TI  - What lies in the future of high-pressure bioscience?
AB  - Without being comprehensive in this mini-review, I will address perspectives,
      some speculative, for the development and use of high pressure to explore
      biochemical phenomena. This will be illustrated with several examples.

PMID- 16275136
TI  - Contribution of the tendinous tissue to force enhancement during stretch
      shortening cycle exercise depends on the prestretch and concentric phase
      intensities.
AB  - When the prestretch intensity and concentric work are increased in stretch
      shortening cycle (SSC) exercises, the utilization of the elastic energy can
      increase during the concentric phase. In order to further understand this process
      during SSC exercises, the interaction between fascicle-tendinous tissues (TT) of
      the vastus lateralis (VL) muscle was examined under different prestretch and
      rebound intensity drop jumps. Ten male subjects participated in the study. Direct
      VL fascicle lengths (N = 10) and in vivo patellar tendon force (N = 1) were
      measured together with the electromyographic (EMG) activity of VL during the
      trials. With increasing drop height but the same rebound height condition, the TT
      stretch increased during the early braking phase with a subsequent increase in
      its recoil during the early push-off phase. This occurred concomitantly with
      decreased fascicle shortening and EMG activation. However, with the increased
      rebound height but the same drop height condition, the fascicles were stretched
      less during the late braking phase with higher EMG activation. In this situation,
      TT could be stretched more by the tension provided by fascicles. Consequently,
      the TT recoil increased during the late push-off phase. These observations
      confirm that there can be an intensity specific fascicle-TT interaction during
      SSC exercises.

PMID- 16275137
TI  - CLASSIC: consistent longitudinal alignment and segmentation for serial image
      computing.
AB  - This paper proposes a temporally consistent and spatially adaptive longitudinal
      MR brain image segmentation algorithm, referred to as CLASSIC, which aims at
      obtaining accurate measurements of rates of change of regional and global brain
      volumes from serial MR images. The algorithm incorporates image-adaptive
      clustering, spatiotemporal smoothness constraints, and image warping to jointly
      segment a series of 3-D MR brain images of the same subject that might be
      undergoing changes due to development, aging, or disease. Morphological changes,
      such as growth or atrophy, are also estimated as part of the algorithm.
      Experimental results on simulated and real longitudinal MR brain images show both
      segmentation accuracy and longitudinal consistency.

PMID- 16275138
TI  - Cerebral pathways in processing of affective prosody: a dynamic causal modeling
      study.
AB  - This study was conducted to investigate the connectivity architecture of neural
      structures involved in processing of emotional speech melody (prosody). 24
      subjects underwent event-related functional magnetic resonance imaging (fMRI)
      while rating the emotional valence of either prosody or semantics of binaurally
      presented adjectives. Conventional analysis of fMRI data revealed activation
      within the right posterior middle temporal gyrus and bilateral inferior frontal
      cortex during evaluation of affective prosody and left temporal pole,
      orbitofrontal, and medial superior frontal cortex during judgment of affective
      semantics. Dynamic causal modeling (DCM) in combination with Bayes factors was
      used to compare competing neurophysiological models with different intrinsic
      connectivity structures and input regions within the network of brain regions
      underlying comprehension of affective prosody. Comparison on group level revealed
      superiority of a model in which the right temporal cortex serves as input region
      as compared to models in which one of the frontal areas is assumed to receive
      external inputs. Moreover, models with parallel information conductance from the
      right temporal cortex were superior to models in which the two frontal lobes
      accomplish serial processing steps. In conclusion, connectivity analysis supports
      the view that evaluation of affective prosody requires prior analysis of acoustic
      features within the temporal and that transfer of information from the temporal
      cortex to the frontal lobes occurs via parallel pathways.

PMID- 16275139
TI  - Classifying brain states and determining the discriminating activation patterns:
      Support Vector Machine on functional MRI data.
AB  - In the present study, we applied the Support Vector Machine (SVM) algorithm to
      perform multivariate classification of brain states from whole functional
      magnetic resonance imaging (fMRI) volumes without prior selection of spatial
      features. In addition, we did a comparative analysis between the SVM and the
      Fisher Linear Discriminant (FLD) classifier. We applied the methods to two
      multisubject attention experiments: a face matching and a location matching task.
      We demonstrate that SVM outperforms FLD in classification performance as well as
      in robustness of the spatial maps obtained (i.e. discriminating volumes). In
      addition, the SVM discrimination maps had greater overlap with the general linear
      model (GLM) analysis compared to the FLD. The analysis presents two phases:
      during the training, the classifier algorithm finds the set of regions by which
      the two brain states can be best distinguished from each other. In the next
      phase, the test phase, given an fMRI volume from a new subject, the classifier
      predicts the subject's instantaneous brain state.

PMID- 16275140
TI  - Dissociable roles of the bilateral anterior temporal lobe in face-name
      associations: an event-related fMRI study.
AB  - Previous studies have suggested the importance of bilateral anterior temporal
      regions in face-name associations, but there is little evidence concerning their
      precise role. In this fMRI study, we investigated the effects of person-related
      semantics (PS) and repeated learning (R) on activations in these regions during
      the retrieval of face-name associations. For encoding stimuli, we prepared four
      lists of faces. To control the factor of PS, people's and occupation names were
      attached to the faces in lists A and B, whereas only people's names were attached
      to the faces in lists C and D. To control the factor of R, the stimuli in lists A
      and C were learned twice, whereas the stimuli in lists B and D were learned seven
      times during encoding before fMRI. During fMRI after the encoding, subjects
      participated in the retrieval task of people's names from faces or in the
      retrieval task of faces from people's names. The left anterior temporal lobe was
      significantly activated during the retrieval of people's names from faces encoded
      with, compared to without, PS; whereas the right anterior temporal lobe was
      activated during the retrieval of people's faces from names, compared to without,
      this encoding. Also, activation of the left (but not the right) anterior temporal
      lobe was significantly reduced after R of face-name associations. These findings
      suggest that the three components of faces, names, and PS may be mutually
      mediated by the bilateral anterior temporal lobe, whose activity may be
      dynamically changed by the level of consolidation of face-name associations.

PMID- 16275141
TI  - fMRI activity in the medial temporal lobe during famous face processing.
AB  - The current event-related fMRI study examined the relative involvement of
      different parts of the medial temporal lobe (MTL), particularly the contribution
      of hippocampus and perirhinal cortex, in either intentional or incidental
      recognition of famous faces in contrast to unfamiliar faces. Our intention was to
      further explore the controversial contribution of MTL in the processing of
      semantic memory tasks. Subjects viewed a sequence of famous and unfamiliar faces.
      Two tasks were used encouraging attention to either fame or gender. In the fame
      task, the subjects were requested to identify the person when seeing his/her face
      and also to try to generate the name of this person. In the gender task, the
      subjects were asked to conduct a judgement of a person's gender when seeing
      his/her face. The visual processing was hence directed to gender and thereby
      expected to diminish attention to semantic information leading only to a
      "passive" registration of famous and non-familiar faces. Recognition of famous
      faces, in both contrasts, produced significant activations in the MTL. First,
      during the intentional recognition (the person identification task) increased
      activity was observed in the anterolateral part of left hippocampus, in proximity
      to amygdala. Second, during the incidental recognition of famous faces (the
      gender classification task), there was increased activity in the left posterior
      MTL with focus in the perirhinal cortex. Our results suggest that the hippocampus
      may be centrally involved in the intentional retrieval of semantic memories while
      the perirhinal cortex is associated with the incidental recognition of semantic
      information.

PMID- 16275142
TI  - A population audit of first clinic attendance with suspected epilepsy.
AB  - OBJECTIVE: To assess the quality of clinical care at first clinic attendance in
      children with suspected epilepsy from a defined geographical population. METHOD:
      All hospital- and community-based consultant paediatricians in Nottingham City
      region, UK, were asked to collaborate with a retrospective clinical audit
      identifying children seen between January 2001 and March 2002. The British
      Paediatric Neurology Association (BPNA) audit tool (Appleton R, Besag F, Kennedy
      C, et al. An audit of children referred with suspected epilepsy. Seizure
      1998;7(6):489-95) was used to analyse the initial outpatient assessment. RESULTS:
      All consultants agreed to participate. A total of 147 children were identified as
      meeting the inclusion criteria. The sequence of events during the episodes was
      well recorded (91%). Other aspects of the history were less well recorded. Twelve
      percent were given a diagnosis of epilepsy, 26% non-epileptic and 62% uncertain.
      Documentation of early development and school performance was low (41%). Twenty
      four percent of the children had no written documentation confirming physical and
      neurological examination. Documentation describing referral to an epilepsy nurse
      or support group was seen in 11%. Drug treatment and doses and follow-up plans
      were recorded in nearly all cases where applicable. DISCUSSION: A managed
      clinical network for children with epilepsy in Nottingham and the surrounding
      Trent region is currently being discussed which will consider alternative models
      of care for children with epilepsy. A revision of the BPNA audit tool has been
      produced with the BPNA Audit group and is available for other centres via the
      BPNA website's 'clinical toolbox' (http://www.bpna.org.uk/audit).

PMID- 16275143
TI  - Factors that influence high tibial osteotomy results in patients with medial
      gonarthritis: a score to predict the results.
AB  - OBJECTIVE: High tibial osteotomy (HTO) for the treatment of unicompartmental knee
      osteoarthritis in the presence of axial malalignment is recognized as an
      effective treatment for young and active patients. The aim of this study was to
      identify HTO prognostic factors. METHODS: A total of 94 patients who had
      undergone HTO with additive arthroscopy were scored using the "knee injury and
      osteoarthritis outcome score" (KOOS). A KOOS of less than 114 points was judged
      as a poor outcome. RESULTS: A total of 84 patients were available for follow-up
      after a time-interval of 45.9+/-7.6 (range 34-60) months. The KOOS increased from
      46.1+/-11.1 to 120.3+/-40.8. The preoperative varus angle in all patients was 7.5
      degrees +/-1.9 (range 5-14 degrees ). In follow-up the patients had a mean valgus
      angle of 3.7 degrees +/-2.5. Twenty-three patients (27.4%) had suffered a loss of
      correction (0.8 degrees , range 0-2 degrees ). A loss of correction correlated
      with a minor result in tendency. A total of 25 patients (29.8%) had a poor KOOS.
      Factors associated with a poor HTO outcome were a patient history of more than 24
      months, a preoperative KOOS>50 points, obesity, and smoking. However, the results
      were also influenced by radiological findings, such as medial tibial exophyte, a
      medial joint space width of less than 5mm, and intraarticular damage, such as a
      degree IV cartilage defect of the tibia. Gender was also a minor prognostic
      factor. Patient's age and the event of prior surgery did not influence the
      outcome. CONCLUSION: This study identified relevant factors that significantly
      influenced HTO results. It was possible to create a "predictive score" for HTO
      patients. Patients with more than 4 of the poor prognostic factors should chose
      primary arthroplasty.

PMID- 16275144
TI  - Two different stages of epidermal growth factor (EGF) receptor endocytosis are
      sensitive to free ubiquitin depletion produced by proteasome inhibitor MG132.
AB  - Numerous studies implicate proteasomes in the regulation of EGF receptor (EGFR)
      endocytosis on the basis of the ability of inhibitors to decrease EGFR
      degradation, but the exact mechanisms remain obscure. We demonstrated that EGFR
      itself is not a direct target for proteasome, since it is delivered to lysosomes
      intact. Evidence is presented that the inhibitory effect of MG132 on EGF
      degradation is due mostly to free ubiquitin depletion resultant from the
      suppression of proteasomal functioning by MG132. By subcellular fractionation, we
      show two MG132-sensitive steps in the EGFR degradation pathway: sorting from
      early (EE) to late (LE) endosomes, and late stage of LE maturation. MG132
      treatment resulted in stabilization of EGFR tyrosine phosphorylation and its
      association with c-Cbl. Nevertheless, ubiquitination of EGFR at late stages of
      endocytosis was significantly lower than that in control cells. Highly
      ubiquitinated forms of EGFR demonstrated more sensitivity to MG132 treatment.

PMID- 16275145
TI  - Purified human chondroitin-4-sulfate reduced MMP/TIMP imbalance induced by iron
      plus ascorbate in human fibroblast cultures.
AB  - Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitor of matrix
      metalloproteinases (TIMPs) is an important control point in tissue remodelling.
      Several findings have reported a marked MMP/TIMP imbalance in a variety of in
      vitro models in which oxidative stress was induced. Since previous studies showed
      that commercial hyaluronan and chondroitin-4-sulphate are able to limit lipid
      peroxidation during oxidative stress, we investigated the antioxidant capacity of
      purified human plasma chondroitin-4-sulfate in reducing MMP and TIMP imbalance in
      a model of ROS-induced oxidative injury in fibroblast cultures. Purified human
      plasma chondroitin-4-sulfate was added to the fibroblast cultures exposed to
      FeSO4 plus ascorbate. We assayed cell death, MMP and TIMP mRNA expression and
      protein activities, DNA damage, membrane lipid peroxidation, and aconitase
      depletion. FeSO4 plus ascorbate produced severe death of cells and increased MMP
      1, MMP-2 and MMP-9 expression and protein activities. It also caused DNA strand
      breaks, enhanced lipid peroxidation and decreased aconitase. TIMP-1 and TIMP-2
      protein levels and mRNA expression remain unaltered. Purified human plasma C4S,
      at three different doses, restored the MMP/TIMP homeostasis, increased cell
      survival, reduced DNA damage, inhibited lipid peroxidation and limited impairment
      of aconitase. These results further support the hypothesis that these
      biomolecules possess antioxidant activity and by reducing ROS production C4S may
      limit cell injury produced by MMP/TIMP imbalance.

PMID- 16275146
TI  - Expression of silicatein in spicules from the Baikalian sponge Lubomirskia
      baicalensis.
AB  - Lake Baikal harbors the largest diversity of sponge species [phylum Porifera]
      among all freshwater biotopes. The abundantly occurring species Lubomirskia
      baicalensis was used to study the seasonal silicatein metabolism; the spicules of
      this species have an unusually thick axial filament, consisting of silicatein,
      which remains constant in diameter during their growth. In the course of
      maturation, the size of the silicic acid shell grows, until the final diameter of
      the spicules of about 8 microm is reached. The seasonal content of silicatein was
      assessed by use of antibodies raised against silicatein; they stained
      specifically the axial filaments. In addition we determined, by application of
      the enzyme-linked immunosorbent assay system, that the proteinaceous content of
      the spicules, the silicatein, increases from spring to late summer by 8-fold. As
      molecular markers to quantify the seasonal changes in expression levels of genes
      coding for proteins/enzymes, the genes for the calumenin-like protein and the
      kinesin-related protein, were selected. The expression of calumenin-like gene,
      involved in the intracellular signaling, is highest during September, whereas the
      expression of the kinesin-related protein does not change during the annual
      course. These results suggest that the highest metabolic activity of L.
      baicalensis occurs in late summer (September), in parallel with the highest
      accumulation of silicatein, a structural protein/enzyme of the spicules.

PMID- 16275147
TI  - Chemical shift anisotropy amplification with high amplification factor and
      improved sensitivity.
AB  - An improved version of the recently proposed chemical shift anisotropy
      amplification experiment is described. The original experiment correlates a fast
      magic angle spinning spectrum in the omega2 dimension with a sideband pattern in
      omega1 in which the intensities mimic those for a sample spinning at a fraction
      of the rate omegar/N. Advantages of the experiment include the use of standard
      methods to extract the principal tensor components from the omega1 sideband
      patterns and the small number of t1 increments required. The improved version
      described here permits large amplification factors N to be obtained without
      resort to prohibitively long sequences of pi-pulses and allows sensitivity to be
      maximized by eliminating the need to store the magnetization along the z-axis for
      t1. Amplification factors up to 32 are demonstrated experimentally.

PMID- 16275148
TI  - Novel actions of IGFBP-3 on intracellular signaling pathways of insulin-secreting
      cells.
AB  - Understanding mechanisms underlying apoptotic destruction of insulin-secreting
      cells is critical to validate therapeutic targets for type 1 diabetes mellitus.
      We recently reported insulin-like growth factor binding protein-3 (IGFBP-3) as a
      novel mediator of apoptosis in insulin-secreting cells. In light of emerging IGF
      independent roles for IGFBP-3, we investigated the mechanisms underlying actions
      of the novel, recombinant human mutant G(56)G(80)G(81)-IGFBP-3, which lacks
      intrinsic IGF binding affinity. Using the rat insulinoma RINm5F cell line, we
      report the first studies in insulin-secreting cells that IGFBP-3 selectively
      suppresses multiple, key intracellular phosphorelays. By immunoblot, we
      demonstrate that G(56)G(80)G(81)-IGFBP-3 suppresses phosphorylation of c-raf-MEK
      ERK pathway and p38 kinase in time-dependent and dose-dependent manners. SAPK/JNK
      signaling was unaffected. These data delineate several novel intracellular sites
      of action for IGFBP-3 in insulin-secreting cells.

PMID- 16275150
TI  - Development of V2-deleted trimeric envelope vaccine candidates from human
      immunodeficiency virus type 1 (HIV-1) subtypes B and C.
AB  - The urgent need for a vaccine against HIV/AIDS requires that multiple strategies
      be employed and evaluated in a clinical setting. V2-loop deleted trimeric
      envelope (Env) immunogens (protein and DNA) from subtypes B and C human
      immunodeficiency virus type 1 (HIV-1) strains were produced for ongoing and
      future clinical evaluations with other HIV antigens, adjuvants and deliveries.

PMID- 16275149
TI  - Brain abnormalities in a case of malonyl-CoA decarboxylase deficiency.
AB  - Malonyl-CoA decarboxylase (MCD) deficiency is an extremely rare inborn error of
      metabolism that presents with metabolic acidosis, hypoglycemia, and/or
      cardiomyopathy. Patients also show neurological signs and symptoms that have been
      infrequently reported. We describe a girl with MCD deficiency, whose brain MRI
      shows white matter abnormalities and additionally diffuse pachygyria and
      periventricular heterotopia, consistent with a malformation of cortical
      development. MLYCD-gene sequence analysis shows normal genomic sequence but no
      messenger product, suggesting an abnormality of transcription regulation. Our
      patient has strikingly low appetite, which is interesting in the light of the
      proposed role of malonyl-CoA in the regulation of feeding control, but this
      remains to be confirmed in other patients. Considering the incomplete
      understanding of the role of metabolic pathways in brain development, patients
      with MCD deficiency should be evaluated with brain MRI and unexplained
      malformations of cortical development should be reason for metabolic screening.

PMID- 16275151
TI  - Acoustic cavitation induced by ultrasonic cutting devices: a preliminary study.
AB  - Ultrasonic cutting is frequently used for the separation of foods, especially in
      case of commodities with multiple layers showing a different mechanical
      resistance. Both chemiluminescence measurements and the degradation of
      organochloric compounds served as an evidence for the occurrence of acoustic
      cavitation around excited cutting blades. Additionally, sensory experiments
      revealed that even a short ultrasonic treatment of edible oil is sufficient to
      generate a remarkable off-flavor.

PMID- 16275152
TI  - First-order system least-squares (FOSLS) for modeling blood flow.
AB  - The modeling of blood flow through a compliant vessel requires solving a system
      of coupled nonlinear partial differential equations (PDEs). Traditional methods
      for solving the system of PDEs do not scale optimally, i.e., doubling the
      discrete problem size results in a computational time increase of more than a
      factor of 2. However, the development of multigrid algorithms and, more recently,
      the first-order system least-squares (FOSLS) finite-element formulation has
      enabled optimal computational scalability for an ever increasing set of problems.
      Previous work has demonstrated, and in some cases proved, optimal computational
      scalability in solving Stokes, Navier-Stokes, elasticity, and elliptic grid
      generation problems separately. Additionally, coupled fluid-elastic systems have
      been solved in an optimal manner in 2D for some geometries. This paper presents a
      FOSLS approach for solving a 3D model of blood flow in a compliant vessel. Blood
      is modeled as a Newtonian fluid, and the vessel wall is modeled as a linear
      elastic material of finite thickness. The approach is demonstrated on three
      different geometries, and optimal scalability is shown to occur over a range of
      problem sizes. The FOSLS formulation has other benefits, including that the
      functional is a sharp, a posteriori error measure.

PMID- 16275153
TI  - A new method for processing of continuous intracranial pressure signals.
AB  - This paper describes a new method for processing of continuous pressure signals.
      Continuous intracranial pressure (ICP) signals were sampled at 100 Hz, converted
      into digital data and processed during 6s time windows. According to a new
      algorithm, cardiac beat-induced single ICP waves were identified; pressure waves
      caused by noise in the signal were rejected for further analysis. The amplitude
      and latency values of the accepted single ICP waves were determined. For accepted
      6s time windows, the mean ICP wave was computed as mean ICP wave amplitude and
      mean ICP wave latency. Mean ICP for every time window was computed according to
      current practice as sum of pressure levels divided by number of samples. The mean
      ICP wave parameters provide information about the single ICP waves that is not
      given by mean ICP. The method has been implemented in software to be used during
      online ICP monitoring, revealing mean ICP wave amplitude, mean ICP wave latency
      and mean ICP as numerical values every 6s. The values are presented in trend
      plots. Verification of correct single ICP wave identification can be done during
      online ICP monitoring. The clinical significance of the method was illustrated in
      four patients by observations that mean wave amplitudes corresponded better to
      the acute clinical state than the mean ICP; mean wave amplitudes could be
      elevated despite a normal mean ICP. In one patient with ICP and arterial blood
      pressure (ABP) signals monitored simultaneously with identical time reference,
      there was a weak correlation between mean ICP and ABP wave amplitudes. It is
      tentatively suggested that the mean ICP wave parameters are related to
      intracranial pressure-volume compensatory reserve capacity (compliance).

PMID- 16275154
TI  - Medical suicide -- groin stabbing.
AB  - This case report concerns a 50-year-old male who died from exsanguination due to
      self-inflicted stabbing injuries to the groin and cutting injuries to the neck.
      He was a medical doctor suffering from depression following treatment for cancer.
      Postmortem examination revealed that stab injuries in the groin were directly
      over the femoral arteries where the femoral pulse is clinically palpated. The
      injury pattern of this suicidal stabbing is uncommon and the medical knowledge of
      this person may have well contributed to the choice of the site.

PMID- 16275155
TI  - Forebrain emotional asymmetry: a neuroanatomical basis?
AB  - There is considerable psychophysiological evidence to indicate that the left and
      right halves of the human forebrain differentially associate with particular
      emotions and affective traits. A neurobiological model is needed. Here I propose
      that forebrain emotional asymmetry is anatomically based on an asymmetrical
      representation of homeostatic activity that originates from asymmetries in the
      peripheral autonomic nervous system. This proposal builds on recent evidence
      indicating that lateralized, higher-order re-representations of homeostatic
      sensory activity provide a foundation for subjective human feelings. It can
      subsume differing views of emotion and the forebrain because it suggests that
      emotions are organized according to the fundamental principle of autonomic
      opponency for the management of physical and mental energy.

PMID- 16275156
TI  - Jaw osteonecrosis associated with bisphosphonates: multiple exposed areas and its
      relationship to teeth extractions. Study of 20 cases.

PMID- 16275157
TI  - The role of genetic polymorphisms in the promoters of the matrix
      metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 genes in head and
      neck cancer.
AB  - Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases
      (TIMPs) play an important role in several stages of cancer initiation and
      development. Single nucleotide polymorphisms identified in the promoters of MMP2
      (-1306C-->T) and TIMP2 (-418G-->C) abolish the Sp1-binding site and thus may down
      regulate expression of the genes. We examined the contribution of these
      polymorphisms to susceptibility and aggressiveness of head and neck squamous cell
      carcinoma (HNSCC). MMP2 genotypes were determined by PCR-based allele-specific
      refractory mutation analysis and TIMP2 genotypes identified by PCR-RFLP in a
      panel of HNSCC cell lines and in 239 head and neck cancer patients and 250
      frequency matched controls in an ethnic Thai population. We found that subjects
      with the MMP2 CC genotype was associated with significantly increased risk
      [adjusted odds ratio (OR), 1.97; 95% confidence interval (95% CI), 1.23-3.15] for
      developing HNSCC compared with those with the variant genotype (-1306CT or TT).
      For TIMP2, a moderately increased risk of the cancer (OR, 1.43; 95% CI, 0.98
      2.08) was also associated with the variant allele (-418GC or CC), compared with
      the GG common allele. Furthermore, the polymorphisms in both genes showed some
      additive effect and the highest risk for head and neck cancer was observed in
      those with MMP2 CC genotype and TIMP2 variant GC or CC genotype (OR, 2.34; 95%
      CI, 1.31-4.18). A correlation between promoter polymorphisms and the levels of
      mRNA expression in cell lines and cancer tissues was found. Finally, the MMP2 CC
      genotype was correlated with adverse clinicopathological variables. These
      findings suggest that the genetic polymorphisms in the promoters of MMP2 and
      TIMP2 may be associated with the development and aggressiveness of HNSCC.

PMID- 16275158
TI  - Study of inclusion complex formation between tropaeolin OO and beta-cyclodextrin
      by spectrophotometry and Infrared spectroscopy.
AB  - The mechanism of the inclusion of tropaeolin OO (TPOO) and beta-cyclodextrin
      (beta-CD) has been studied by spectrophotometry. The inclusion depth of the guest
      molecule in the host molecule was demonstrated by infrared spectrometry. Effect
      of the pH, concentrations of beta-CD, solvents and ionic strength on the
      inclusion of TPOO and beta-CD were examined. The result showed that TPOO reacts
      with beta-CD to form a 1:1 host-guest complex with an apparent formation constant
      of 1.50 x 10(3) l mol(-1). The thermodynamic parameters of inclusion reaction,
      DeltaG degrees , DeltaH degrees and DeltaS degrees were obtained.

PMID- 16275159
TI  - E-health progresses in Romania.
AB  - The paper is presenting the recent evolution of e-health aspects in Romania. Data
      presented are based on governmental reports. Surveys organized by the "Lucian
      Blaga" University of Sibiu and studies carried on by the national Institute for
      Research and Development in Informatics (I.C.I.) have shown that Romania has
      important health problems, from cardio vascular diseases (CVD) to cancer and
      infectious diseases, a high score on mortality and morbidity and a low one on
      natality. Poor management of the health sector did not help to solve all these
      problems. In the last 14 years there were several attempts to reform healthcare
      but none succeeded until now. The health insurance system is operational but
      needs still to be improved. Acknowledging the deep crisis of the health system
      the Prime Minister nominated a new minister of health and important changes in
      the health management approach are to be envisaged. One of this is the
      introduction of the e-procurement system for all health related goods. In spite
      of the crisis of the health system, e-health applications are flourishing. We can
      distinguish applications at national and local level and also punctual
      applications. The main applications refer to hospital information systems (HIS),
      electronic health records (EHR), e-procurement, image processing, diagnosis and
      treatment aids, telediagnosis, teleconsultation, education, research and domain
      oriented web support services. Most academic clinical hospital is now members of
      a web community "mednet". Unfortunately a lot of medical web sites have
      disappeared for lack of funds. As the health sector is in general funded from the
      public budget and the health crisis is deepened in the last years, the driving
      force in implementing e-health concepts and technologies is not the Ministry of
      Health but the Information Technology (IT) community, with a strong support from
      the Ministry of Information Technology and Communications and also from the
      Ministry of Education and Research, the Romanian Academy and professional non
      governmental organizations. Our government has established the strategy for
      achieving the e-society for almost all domains but healthcare is still the
      Cinderella. It is expected that IT will play the role of the Fair Godmother by
      improving the general health status of the population through a better management
      of health services and better access to information and knowledge, for both major
      actors: the health professionals and the citizens.

PMID- 16275160
TI  - Detection of conjugated dienoic fatty acids in human vascular smooth muscle cells
      treated with conjugated linoleic acid.
AB  - Conjugated linoleic acids (CLA) have attracted scientific interest due to their
      potential beneficial effects on atherosclerosis. Recent studies demonstrated that
      conjugated metabolites of CLA are found in tissues of CLA-fed animals and
      cultured cells treated with CLA. This observation has gained in importance since
      it has recently been shown that these metabolites of CLA exert specific
      biological activities. Therefore, the present study aimed to explore the
      potential formation of metabolites of cis-9, trans-11 CLA, trans-10, cis-12 CLA
      and trans-9, trans-11 CLA in cells of the vascular wall, which has not yet been
      shown. Examination of fatty acid composition of total cell lipids using Ag+-HPLC,
      GC-FID and GC-MS analysis revealed a significant isomer-specific formation of
      conjugated metabolites of CLA such as CD16:2, CD20:2 and CD22:2 in human coronary
      artery smooth muscle cells treated with various CLA isomers. Different CD16:2/CLA
      ratios between various CLA isomers as observed in the present study indicate that
      fatty acid metabolism is differently affected by the configuration of the double
      bonds. In conclusion, the observation from the present study suggests that the
      effects of CLA in vascular cells might not only be mediated by CLA itself but
      also by its conjugated metabolites. Future studies using highly purified
      conjugated metabolites of CLA are necessary to study their role in mediating
      biological effects of CLA in cell culture systems.

PMID- 16275162
TI  - Efficient control of gene expression in the hematopoietic system using a single
      Tet-on inducible lentiviral vector.
AB  - This work addresses the problem of efficient control of gene expression in the
      context of viral vectors, which still represents a difficult challenge. A number
      of lentiviral vectors incorporating the different elements of regulatable
      transcriptional systems have been described, but they fail to perform
      satisfactorily either because of a poor dynamic range of transcription levels or
      because they display high background activities in the uninduced state and
      mediocre inducer response. We report here on the systematic comparison of vector
      designs containing the elements of the doxycycline-inducible Tet-on system in
      their most advanced versions (rtTA2S-M2 transactivator and tTS(Kid) repressor).
      We show that a simple "all-in-one" vector can be obtained and used for efficient
      control of transgene expression in long-term tissue culture and in the
      hematopoietic system of mice following bone marrow transplantation. Using this
      vector, the uninduced state can be kept at background levels and induction
      factors of 100-fold are repeatedly obtained over months both in tissue culture
      and in vivo. Interestingly, the low background activity of the all-in-one vector
      renders the use of the tTS repressor dispensable, avoiding the problem of
      progressive loss of inducibility over time associated with irreversible
      modifications of the chromatin surrounding proviral sequences.

PMID- 16275163
TI  - Immunization with a lentiviral vector stimulates both CD4 and CD8 T cell
      responses to an ovalbumin transgene.
AB  - Lentiviral vectors encoding antigens are promising vaccine candidates because
      they transduce dendritic cells (DC) in vivo and prime CTL responses. Here we
      examine their stimulation of antigen-specific CD4(+) T cells, critical for
      protective immunity against tumors or infectious disease. We constructed
      lentiviral vectors (lentivectors) expressing ovalbumin, which was secreted (OVA),
      cytoplasmic (OVAcyt), or fused to either invariant chain (Ii-OVA) or transferrin
      receptor (TfR-OVA) sequences, targeting the MHC class II presentation pathway.
      Murine DC infected with the various lentivectors could stimulate OT-I (CD8(+),
      OVA TCR transgenic) T cells and all except OVAcyt could also stimulate OT-II
      (CD4(+), OVA TCR transgenic) T cells in vitro. Direct injection of the OVA-, Ii
      OVA-, or TfR-OVA-expressing vectors into mice resulted in a CD4(+) T cell
      response, as shown by expansion of adoptively transferred OT-II T cells and
      upregulation of CD44 on these cells. The Ii-OVA vector was the most potent
      inducer of IFN-gamma-secreting CD4(+) and CD8(+) T cells and was the only vector
      to protect mice completely from challenge with OVA-expressing tumor cells.
      Therefore directly injected lentivectors can stimulate CD4(+) T cells; both
      CD4(+) and CD8(+) responses can be enhanced by targeting the antigen to the MHC
      class II pathway.

PMID- 16275164
TI  - Interface between endocrinology and psychiatry in women with epilepsy: analysis
      of the relationship with comorbid pathology.
AB  - This study was carried out to detect a possible association between endocrine
      pathology, neurological symptoms, and psychiatric variables in women with
      epilepsy. One hundred and thirty epileptic women with childbearing potential were
      recruited into the study. The results obtained showed that catamenial epilepsy
      was observed mainly in women with reproductive dysfunction and normal thyroid
      function. There was a reciprocal relationship between thyroid and reproductive
      pathology. Catameniality interacted with reproductive dysfunction, thyroid state,
      and focus laterality and determined not only the frequency of certain seizures
      but also psychopathological constructs of the SCL-90 scale. It was concluded that
      catameniality should be a topic of further research.

PMID- 16275166
TI  - The US experience with cilostazol in treating intermittent claudication.
AB  - The management of peripheral arterial disease (PAD) patients with intermittent
      claudication (IC) requires both aggressive risk management and targeted
      symptomatic therapies. The phosphodiesterase inhibitor cilostazol is the only US
      Food and Drug Administration (FDA) approved medication to demonstrate consistent
      benefits on both objective measures of exercise capacity and subjective measures
      of everyday functioning and quality of life. Pentoxifylline is also approved by
      the FDA for the treatment of claudication, but with less clinical benefit than
      cilostazol. This report will provide an overview of cilostazol's role in the
      treatment of patients with IC. Data will be presented regarding the safety and
      efficacy demonstrated by cilostazol in clinical trials, as well as the effects of
      risk-factor control, exercise therapy, revascularization, and experimental drugs
      on the treatment of claudication in the PAD population. Based on the available
      evidence, a comprehensive approach to claudication management is recommended.

PMID- 16275167
TI  - A scientific rationale for the CREST trial results: evidence for the mechanism of
      action of cilostazol in restenosis.
AB  - The Cilostazol for RESTenosis (CREST) clinical trial was initiated to evaluate
      the efficacy of cilostazol, an antiplatelet drug, in inhibiting restenosis after
      stent implantation in a native coronary artery as evaluated by quantitative
      coronary angiography. Preliminary results suggest that cilostazol reduces
      restenosis by 36% over standard therapy alone. Restenosis after coronary stenting
      is primarily attributed to neointimal formation. Cilostazol decreases the
      activity of phosphodiesterase type 3, leading to the accumulation of cyclic
      adenosine monophosphate, which initiates a cascade of events including
      upregulation of anti-oncogenes p53 and p21 and upregulation of hepatocyte growth
      factor (HGF). The increase in p53 protein blocks cell cycle progression and
      induces apoptosis in vascular smooth muscle cells (VSMCs), leading to an
      antiproliferative effect. Upregulation of local HGF stimulates rapid regeneration
      of endothelial cells, which inhibits neointimal formation via two mechanisms:
      inhibition of abnormal VSMC growth and improvement of endothelial function. These
      mechanisms may be responsible for the improvement in restenosis shown in the
      CREST trial and a number of other trials in patients who underwent percutaneous
      transluminal coronary angioplasty. These effects, in addition to antithrombotic
      and vasodilatory attributes of cilostazol, make it a potentially viable treatment
      option for preventing restenosis following coronary stenting.

PMID- 16275168
TI  - Effect on platelet function of cilostazol, clopidogrel, and aspirin, each alone
      or in combination.
AB  - Management of peripheral arterial disease (PAD) requires standard atherosclerotic
      risk management interventions. However, PAD is often complicated by walking pain
      (intermittent claudication [IC]), which requires symptom-specific therapies as
      well. Thus, all PAD patients are encouraged to take antiplatelet agents to reduce
      the associated risks of major cardiovascular events, and those with IC may also
      require treatment with cilostazol, an agent proven to increase exercise capacity
      and enhance quality of life in these patients. Although it was initially thought
      that cilostazol's antiplatelet properties might render it unsafe to use in
      combination with other platelet inhibitors because of possible additive effects,
      a recent study has dispelled such concerns. There is evidence that in a crossover
      trial of 21 patients with PAD and IC, aspirin alone, or clopidogrel alone,
      significantly increased bleeding times, but cilostazol alone did not. The
      combination of aspirin and clopidogrel had a greater effect on increasing
      bleeding time than either monotherapy, and no further bleeding time prolongation
      was observed, when cilostazol was added to any aspirin/clopidogrel regimen. These
      findings suggest that PAD patients with IC may be safely managed with both
      cilostazol and standard antiplatelet therapy, without increasing the risk of
      adverse bleeding effects.

PMID- 16275169
TI  - Cilostazol: potential mechanism of action for antithrombotic effects accompanied
      by a low rate of bleeding.
AB  - Treatment of thrombotic disease requires a delicate balance between prevention of
      new thrombotic events and management of bleeding complications. Various
      antiplatelet and anticoagulant agents have been used to this end, with varying
      degrees of success. Among the antiplatelet agents tested so far, cilostazol,
      which selectively targets phosphodiesterase III (PDE-III), has unique features.
      Cilostazol is classified as an antiplatelet agent because it inhibits the
      platelet aggregation induced by collagen, 5'-adenosine diphosphate (ADP),
      epinephrine, and arachidonic acid. Unlike other antiplatelet agents cilostazol
      not only inhibits platelet function but also improves endothelial cell function.
      Platelets circulate throughout the body with continuous tethering on the surface
      of endothelial cells. When endothelial cells are stimulated, the number of
      activated, or pre-conditioned, platelets in circulation increases. These
      platelets enhance thrombus formation at the sites of endothelial disruption.
      Cilostazol effectively prevents the onset of thrombotic disease, not only by
      direct inhibition of platelet function, but also by reducing the number of
      activated or pre-conditioned platelets in circulation. Secondary prevention of
      stroke with modest increase in bleeding complications was achieved by
      administration of cilostazol in the Japanese Cilostazol Stroke Prevention Study
      done in Japan. These results suggest that cilostazol may reduce the risk of
      stroke without increasing the risk of bleeding complications.

PMID- 16275170
TI  - Mitochondrial effects on flower and pollen development.

PMID- 16275171
TI  - Cystic fibrosis mutations and genotype-pulmonary phenotype analysis.
AB  - BACKGROUND: Although there are more than 1000 mutations in the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene, most of them are uncommon and
      only limited information exists regarding genotype-pulmonary phenotype
      relationships. METHODS: We determined and classified the CFTR mutations using
      denaturing high-performance liquid chromatography and developed new, quantitative
      methods to categorize pulmonary phenotypes. RESULTS: Two novel alleles were
      discovered, namely G1047R and 1525-2A-->G, which were accompanied by F508del and
      G551D mutations, respectively. Assessment of numerous options revealed that CF
      pulmonary phenotype categorization in children cannot be accomplished with
      clinical or pulmonary function data but is facilitated by longitudinal
      quantitative chest radiology. It was most useful to categorize pulmonary disease
      status by evaluating the typical pattern of abnormalities in patients homozygous
      for the F508del mutation, and then compare patients with minor mutations to this
      typical CF pulmonary phenotype. By this method, both patients with novel
      mutations have pulmonary phenotypes typical of F508del homozygotes. However,
      patients with class IV mutations (e.g., R347P) or with pancreatic sufficiency
      showed serial chest radiographs that were atypically mild. CONCLUSIONS:
      Longitudinal quantitative chest radiography provides a new strategy for CF
      pulmonary phenotype categorization that should be useful for genotype-phenotype
      delineation in individual patients and in both epidemiologic studies and clinical
      trials involving groups of children with CF.

PMID- 16275172
TI  - Application of microemulsion thin layer chromatography for the fingerprinting of
      licorice (Glycyrrhiza spp.).
AB  - Microemulsion thin layer chromatography (ME-TLC) has been developed for the
      fingerprinting of aqueous extract of licorice (Glycyrrhiza spp.). The separation
      conditions and operational processes of the method have been optimized, and its
      chromatographic characteristics compared with conventional TLC. The ME-TLC system
      is easier to operate, and with higher resolution and better reproducibility than
      the conventional TLC. The separation mechanism and retention behavior of ME-TLC
      are found to differ significantly from conventional TLC. The technique has been
      applied to the analysis of different licorice species including G. uralensis, G.
      glabra and G. inflata; and to monitor the dynamic accumulation of active
      ingredients in licorice plant harvested at different times during its growing
      cycle in a Good Agriculture Practice (GAP) research farm. Results show that
      without post-chromatographic derivatization, the ME-TLC fingerprinting images of
      different species appear as clear, well resolved bands and with strong
      intensities to reveal distinctively different compositional features of the
      samples. The technique has also been applied successfully to monitor the dynamic
      accumulation of active components in licorice plant as a function of growing time
      in an experimental licorice farm. The study demonstrates the potential of ME-TLC
      technique as a rapid fingerprinting tool for the authentication and quality
      assessment of licorice as well as other herbs.

PMID- 16275173
TI  - Efficient solubilization buffers for two-dimensional gel electrophoresis of
      acidic and basic proteins extracted from wheat seeds.
AB  - Plant tissues are made up of a broad range of proteins with a variety of
      properties. After extraction, solubilization of a diverse range of plant proteins
      for efficient proteomic analysis using two-dimensional electrophoresis is a
      challenging process. We tested the efficiency of 12 solubilization buffers in
      dissolving acidic and basic proteins extracted from mature seeds of wheat. The
      buffer containing two chaotropes (urea and thiourea), two detergents (3-[(3
      cholamidopropyl) dimethyl-ammonio]-1-propane-sulfonate and N-decyl-N,N-dimethyl-3
      ammonio-1-propane-sulfonate), two reducing agents (dithiothreitol and tris (2
      carboxyethyl) phosphine hydrochloride) and two types of carrier ampholytes
      (BioLyte pH 4-6 and pH 3-10) solubilized the most acidic proteins in the pH range
      between 4 and 7. The buffer made up of urea, thiourea, 3-[(3-cholamidopropyl)
      dimethyl-ammonio]-1-propane-sulfonate, DeStreak reagent (Amersham Biosciences,
      Uppsala, Sweden) and immobilized pH gradient buffer, pH 6-11 (Amersham
      Biosciences) solubilized the most basic proteins in the pH range between 6 and
      11. These two buffers produced two-dimensional gels with high resolution,
      superior quality and maximum number of detectable protein (1425 acidic protein
      and 897 basic protein) spots.

PMID- 16275174
TI  - TGF-beta1 as a marker of delayed fracture healing.

PMID- 16275175
TI  - Role of endochondral ossification of articular cartilage and functional
      adaptation of the subchondral plate in the development of fatigue microcracking
      of joints.
AB  - The mechanisms that regulate functional adaptation of the articular ends of long
      bones are poorly understood. However, endochondral ossification of articular
      cartilage and modeling/remodeling of the subchondral plate and epiphyseal
      trabeculae are important components of the adaptive response. We performed a
      histologic study of the distal end of the third metacarpal/metatarsal bone of
      Thoroughbreds after bones were bulk-stained in basic fuchsin and calcified
      sections were prepared. The Thoroughbred racehorse is a model of an extreme
      athlete which experiences particularly high cyclic strains in distal limb bones.
      The following variables were quantified: microcrack boundary density in calcified
      cartilage (N.Cr/B.Bd); blood vessel boundary density in calcified cartilage
      (N.Ve/B.Bd); calcified cartilage width (Cl.Cg.Wi); duplication of the tidemark;
      and bone volume fraction of the subchondral plate (B.Ar/T.Ar). Measurements were
      made in five joint regions (lateral condyle and condylar groove; sagittal ridge;
      medial condylar and condylar groove). N.Cr/B.Bd was site-specific and was
      increased in the condylar groove region; this is the joint region from which
      parasagittal articular fatigue (condylar) fractures are typically propagated.
      Formation of resorption spaces in the subchondral plate was co-localized with
      microcracking. N.Ve/B.Bd was also site-specific. In the sagittal ridge region,
      N.Ve/B.Bd was increased, Cl.Cg.Wi was decreased, and B.Ar/T.Ar was decreased,
      when compared with the other joint regions. Multiple tidemarks were seen in all
      joint regions. Cumulative athletic activity was associated with a significant
      decrease in B.Ar/T.Ar in the condylar groove regions. N.Cr/B.Bd was positively
      correlated with B.Ar/T.Ar (P < 0.05, r(s) = 0.29) and N.Ve/B.Bd was negatively
      correlated with B.Ar/T.Ar (P < 0.005, r2 = 0.14) and Cl.Cg.Wi (P < 0.05, r2 =
      0.07). We conclude that endochondral ossification of articular cartilage and
      modeling/remodeling of the subchondral plate promote initiation and propagation
      of site-specific fatigue microcracking of the joint surface, respectively, in
      this model. Microcracking of articular calcified cartilage likely represents
      mechanical failure of the joint surface. Propagation of microcracks into the
      subchondral plate is a critical factor in the pathogenesis of articular condylar
      fatigue (stress) fracture. Functional adaptation of the joint likely protects
      hyaline cartilage from injury in the short-term but may promote joint
      degeneration and osteoarthritis with ongoing athleticism.

PMID- 16275177
TI  - Anatomic distribution of myocardial ischemia as a determinant of exercise-induced
      ST-segment depression.
AB  - Cardiac single-photon emission computed tomographic correlates of ST depression
      were examined in 129 subjects who had inducible ST depression of > or =0.1 mV and
      reversible perfusion defects. Patients were separated on the basis of single
      photon emission computed tomographic defect distribution into a group with
      anatomically contiguous ischemia (anterior or posterior/inferior defects, n = 68)
      and a group with anatomically opposed ischemia (anterior and posterior/inferior
      defects, n = 61). ST depression in the contiguous ischemia group correlated with
      defect size (r = 0.40, p = 0.001) and severity (r = 0.38, p = 0.002);
      multivariate regression demonstrated each to be independent determinants of ST
      depression magnitude (r = 0.51, p <0.001). In the opposed ischemia group, ST
      depression did not significantly correlate with defect extent or severity. After
      adjusting for differences in perfusion indexes, ST depression was paradoxically
      greater in the contiguous than in the opposed group (2.82 +/- 1.15 vs 2.44 +/-
      1.15 mm, p <0.001). In conclusion, these findings demonstrate that the anatomic
      distribution of ischemia can alter the relation between ST depression and
      functional indexes of ischemia and may confound the accuracy of assessments of
      coronary artery disease based on ST-depression magnitude alone.

PMID- 16275176
TI  - Fourteen-year (1987 to 2000) trends in the attack rates of, therapy for, and
      mortality from non-ST-elevation acute coronary syndromes in four United States
      communities.
AB  - During the past 2 decades, randomized trials have proved the efficacy of several
      treatments for non-ST-elevation acute coronary syndromes (NSTE-ACSs), including
      aspirin, beta blockers, and coronary revascularization. However, the cumulative
      effectiveness of these evolving therapies in actual clinical practice remains
      unknown. The Atherosclerosis Risk In Communities (ARIC) surveillance study uses
      rigorous prospective community surveillance to monitor the epidemiology of
      coronary heart disease among subjects who are 35 to 74 years of age and reside in
      4 United States communities, with a population totaling 370,000 subjects. We
      identified 6,379 ARIC surveillance patients who were hospitalized with NSTE-ACS
      (defined as cardiac chest pain and ST depression or T-wave inversion on the
      presenting electrocardiogram) between 1987 and 2000 and then analyzed 30-day and
      1-year mortalities by calendar year of admission. Using logistic regression, 30
      day mortality was modeled first using predictor variables of the calendar year,
      ARIC community, and indicators of severity and co-morbidity and then by adding
      variables for treatment with aspirin, beta blockers, and coronary
      revascularization to this model. Crude 30-day mortality decreased from 8.6% in
      1988 to 3.6% in 2000 (p for trend <0.001), a trend that remained significant (p =
      0.006) after adjustment for case severity and co-morbidity. The trend became
      nonsignificant after adjustment for treatment variables, suggesting that newer
      treatments may explain the improved survival. In conclusion, 30-day mortality
      from NSTE-ACS has decreased as treatment has improved.

PMID- 16275179
TI  - Plasma, serum, and platelet expression of CD40 ligand in adults with
      cardiovascular disease.
AB  - The application of soluble CD40 ligand (sCD40L) as a biomarker has garnered great
      scientific and clinical interest. However, there are many uncertainties with
      regard to the biology of sCD40L. Although presumed to be a marker of platelet
      activation, relative levels in plasma, serum, and platelet expression are
      unknown, as is the optimal method for its measurement. We measured CD40L from
      serum, platelet-poor plasma, and platelet surface in adults who had stable
      cardiovascular disease (CVD) and those who had unstable CVD (n = 40). Plasma
      sCD40L did not differ significantly between groups. Serum sCD40L was
      significantly lower (1.4 +/- 1.3 vs 5.2 +/- 3.7 ng/ml, p <0.001) and platelet
      membrane CD40L expression was higher (1.4 +/- 0.7% vs 0.9 +/- 0.6%, p = 0.03) in
      unstable compared with stable CVD. When the 2 groups were considered together,
      there was a significant correlation between plasma and serum sCD40L levels (rho =
      0.4, p = 0.02) and negative correlations between plasma (rho = -0.3, p = 0.04)
      and serum (rho = -0.4, p = 0.01) sCD40L levels with platelet membrane CD40L
      expression. In unstable CVD, the correlation between sCD40L measurements was
      poor. Consistent with enhanced platelet activation, there was a positive
      correlation between platelet aggregation and surface CD40L expression (rho = 0.5,
      p = 0.02) and between platelet expression of CD40L and P-selectin (rho = 0.4, p =
      0.05) in unstable CVD. There was no correlation between CD40L and platelet count
      or C-reactive protein. Only surface expression of CD40L compared with platelet
      derived (plasma) or total (serum) CD40L level proved a reliable marker of
      platelet function in patients who had stable CVD and those who had unstable CVD.
      In conclusion, our data demonstrate the complex nature of CD40L and highlight the
      distinct processes of expression, shedding, and clearance of this ligand in
      patient populations.

PMID- 16275178
TI  - Effect of intensive versus moderate lipid lowering on endothelial function and
      vascular responsiveness to angiotensin II in stable coronary artery disease.
AB  - Recent evidence has demonstrated that intensive lipid-lowering therapy with a
      high-dose statin provides significant clinical benefit beyond moderate lipid
      lowering therapy. However, dose-dependent effects of short-term statin therapy on
      vascular function have not been demonstrated. We studied endothelial function and
      vascular responsiveness to angiotensin II in patients who had coronary artery
      diseased and were randomized to receive low- or high-dose atorvastatin (10 or 80
      mg, respectively) or placebo. Internal thoracic artery segments were obtained
      during coronary bypass surgery and studied in vitro. Endothelium-dependent
      vasodilation was increased with atorvastatin therapy (p = 0.035) but was
      significantly increased further in patients who received 80 mg compared with
      those who received 10 mg of atorvastatin (p = 0.05). Endothelium improvement was
      accompanied by decreased vascular response to angiotensin II (p = 0.039). These
      findings suggest a mechanism for the clinical benefit of intensive lipid-lowering
      treatment in coronary heart disease.

PMID- 16275180
TI  - B-type natriuretic peptide levels in patients in the emergency department with
      possible heart failure and previous stable angina pectoris and/or healed
      myocardial infarction.
AB  - We examined the relation between B-type natriuretic peptide (BNP) levels and a
      history of stable angina pectoris and/or healed myocardial infarction in 1,240
      patients who were evaluated in the emergency department for possible heart
      failure. In patients who had heart failure, there was no relation between BNP
      levels and previous stable angina pectoris and/or healed myocardial infarction.
      However, in patients who did not have heart failure, there was a relation between
      BNP levels and previous stable angina pectoris and/or healed myocardial
      infarction but no significant independent relation in multiple regression
      analysis.

PMID- 16275181
TI  - Comparison of usefulness of inflammatory markers in patients with versus without
      peripheral arterial disease in predicting adverse cardiovascular outcomes
      (myocardial infarction, stroke, and death).
AB  - We tested the hypothesis that a combination of measurements of different aspects
      of atherosclerosis, including burden of atherosclerosis and levels of
      inflammation, would contain more predictive information than either alone in an
      outpatient population. We enrolled 110 patients (62 +/- 15 years of age) who were
      referred to the noninvasive vascular laboratory for sequential Doppler pressure
      measurements of the lower extremities. We measured ankle-brachial index (ABI) and
      serum markers of inflammation and followed subjects for a mean of 2.25 years.
      Fifty subjects did not have peripheral arterial disease (PAD; ABI > or =0.9),
      whereas 60 did (ABI <0.9). Markers of inflammation, including C-reactive protein
      (3.83 +/- 0.9 vs 2.11 +/- 1.1, p = 0.019), were higher in subjects who had PAD.
      During follow-up, 42% developed an event (myocardial infarction, stroke,
      unplanned coronary or lower extremity revascularization, or death). Decreasing
      ABI (chi-square 7.3, p = 0.026) and increasing C-reactive protein (chi-square
      22.1, p <0.001) increased the risk of an event. Risk increased sixfold between
      the lowest and highest groups for all events and fourfold for hard events
      (myocardial infarction, stroke, and death) using both C-reactive protein and ABI.
      In conclusion, patients who have PAD and increased inflammation are at highest
      risk for adverse cardiovascular outcomes. Characterizing atherosclerosis on the
      basis of these parameters provides important prognostic information.

PMID- 16275182
TI  - Bleeding complications in patients with anemia and acute myocardial infarction.
AB  - Anemia has recently been associated with increased mortality in patients who
      undergo percutaneous coronary intervention. The mechanisms associated with
      increased mortality among patients who have anemia have not been defined. We
      sought to determine whether patients who had anemia and acute myocardial
      infarction (AMI) might be at higher risk for bleeding or cardiogenic shock during
      acute hospitalization compared with patients who did not have anemia. This
      population-based study included 5,378 residents of the Worcester metropolitan
      area who were hospitalized with a diagnosis of AMI in five 1-year periods from
      1995 to 2003. Patients were analyzed according to the presence or absence of
      anemia (hematocrit <39% in men and <36% in women) and quintiles of baseline
      hematocrit levels. Differences in the frequency of death, cardiogenic shock, and
      major bleeding during hospitalization were analyzed in relation to the presence
      of anemia. Anemia was present in 31.3% of patients who were hospitalized with
      AMI. Mortality and bleeding complications were related to the presence of anemia
      on admission for all types of AMI and across a broad spectrum of anemia
      severities. In a multivariable model that adjusted for baseline and treatment
      covariates, the odds ratios for adverse events for patients who had anemia
      (compared with those who did not) were 1.43 (95% confidence interval 1.12 to
      1.84) for hospital mortality and 3.57 (95% confidence interval 2.75 to 4.64) for
      major bleeding. Development of cardiogenic shock was not related to the presence
      of anemia (odds ratio 0.89, 95% confidence interval 0.64 to 1.23). In conclusion,
      these findings suggest that bleeding complications are a potential mechanism for
      increased mortality among patients who have anemia and present with AMI.

PMID- 16275183
TI  - Comparison of effects of drug-eluting stents versus bare metal stents on plasma C
      reactive protein levels.
AB  - After coronary stenting, inflammatory mechanisms play a crucial role in the
      pathogenesis of neointimal proliferation and in-stent restenosis. Drug-eluting
      stents (DESs) have been shown to decrease in-stent restenosis in different
      studies. We compared plasma C-reactive protein (CRP) levels after DES
      implantation with levels after bare metal stent (BMS) implantation. We performed
      percutaneous coronary intervention with a single stent in 67 patients (54 men; 59
      +/- 9 years of age; n = 21 in the BMS group, n = 46 in the DES group) who had
      stable angina. Plasma CRP levels were determined before intervention and at 48
      hours, 72 hours, and 2 weeks after coronary stenting. There was no difference in
      clinical and angiographic baseline characteristics except that the DES group had
      more patients with diabetes (34.8% vs 9.5%, p = 0.04), smaller reference vessels
      (2.95 +/- 0.53 vs 3.29 +/- 0.53 mm, p = 0.02), and smaller stent diameters (3.0
      +/- 0.4 mm vs 3.4 +/- 0.5 mm, p <0.01). Plasma CRP levels at 48 hours (13.4 +/-
      14.7 vs 5.9 +/- 4.9 mg/L, p <0.01) and 72 hours (16.7 +/- 19.8 vs 5.4 +/- 3.9
      mg/L, p <0.01) after stent implantation were significantly higher in the BMS than
      in the DES group. In conclusion, DESs showed significantly lower plasma CRP
      levels after coronary stenting compared with BMSs. This may reflect the potent
      effects of DESs on acute inflammatory reactions induced by coronary intervention.

PMID- 16275184
TI  - Impact of diabetes mellitus on angiographic and clinical outcomes in the drug
      eluting stents era.
AB  - The effect of diabetes mellitus (DM) on angiographic restenosis and clinical
      outcomes after implantation of drug-eluting stents (DESs) has not been
      investigated in real-world practice. This study consisted of 226 patients who had
      DM and 560 patients who did not who underwent DES implantation between February
      2003 and December 2003. We retrospectively compared the incidence of 6-month
      angiographic restenosis and 9-month major adverse cardiac events (MACEs), defined
      as cardiac death, myocardial infarction, and target lesion revascularization,
      between patients with and without DM. The 6-month angiographic restenotic rate
      (10.1% vs 8.2%, p = 0.41) and late loss (0.41 +/- 0.63 vs 0.36 +/- 0.65, p =
      0.31) were similar between patients with and without DM. In addition, incidences
      of MACEs (4.9% vs 4.8%, p = 1.00) and target lesion revascularization (4.4% vs
      4.1%, p = 0.84) were similar. Patients who had insulin-dependent DM manifested
      higher prevalences of restenosis (25.0% vs 8.5%, p = 0.04) and MACEs (17.2% vs
      3.1%, p = 0.01) compared with patients who had non-insulin-dependent DM. In
      conclusion, in this study of real-world patients who underwent DES implantation,
      patients who had DM had restenotic rates and clinical outcomes that were similar
      to those in patients who did not have DM.

PMID- 16275185
TI  - Effect of sirolimus-eluting stent in diabetic patients with small coronary
      arteries (a SES-SMART substudy).
AB  - Randomized clinical trials have shown that sirolimus-eluting stents (SESs)
      decrease restenosis rates compared with bare metal stents (BMSs), but their
      efficacy among patients who have diabetes mellitus remains to be established.
      This study investigated the effect of SES implantation in a high-risk population
      (i.e., patients who had diabetes and small coronary vessel disease). For this
      purpose, we analyzed outcomes of the subset of patients who had diabetes and were
      enrolled in the SES-SMART, a randomized trial that compared the results of
      implantation of SESs and BMSs in small coronary arteries. Twenty-nine patients
      who had diabetes were originally randomized to receive SESs and 45 patients
      received BMSs. The use of SESs was associated with approximately 60% decreases in
      the relative incidence of in-segment angiographic restenosis (63% vs 25%, p =
      0.003) and in-segment late loss (0.76 vs 0.28 mm, p <0.002). Angiographic
      patterns of restenosis were more favorable in the SES group. SES implantation was
      associated with a 15% absolute decrease in adverse clinical events. In patients
      who had insulin-dependent diabetes mellitus, SESs showed a high in-segment
      restenosis rate (40%) that was principally due to persistent restenosis. In
      conclusion, in diabetics with small coronary arteries, SES implantation
      significantly reduces the incidence of the 8-month angiographic restenosis rate
      compared with BMSs.

PMID- 16275186
TI  - Three-year clinical follow-up after strontium-90/yttrium-90 beta-irradiation for
      the treatment of in-stent coronary restenosis.
AB  - Because late vessel failure has been speculated as a possible limitation of
      vascular brachytherapy, we conducted a prospective clinical evaluation at 6, 12,
      24, and 36 months of follow-up after irradiation with strontium-90/yttrium-90 for
      in-stent restenosis, regardless of the patient's symptomatic status. We report
      complete 3-year follow-up data for 106 consecutive patients. The cumulative rate
      of death at 6, 12, 24, and 36 months was 0.9%, 0.9%, 0.9%, and 1.9% respectively.
      The corresponding rates for acute ST-elevation myocardial infarction were 2.8%,
      4.7%, 4.7%, and 4.7%, respectively. The cumulative rate of late thrombotic
      occlusion at 6, 12, 24, and 36 months was 3.8%, 4.7%, 4.7%, and 4.7%,
      respectively. The corresponding rates of target lesion revascularization and
      target vessel revascularization were 8.5% and 12.3% (p = 0.046), 14.2% (p =
      0.157) and 18.0% (p = 0.046), 12.3% and 18.9% (p = 0.008), and 21.7% (p = 0.083)
      and 29.2% (p = 0.005), respectively. The cumulative rate of all major adverse
      cardiovascular events at 6, 12, 24, and 36 months was 16.1%, 24.5% (p = 0.003),
      27.4% (p = 0.083), and 35.8% (p = 0.003), respectively. In conclusion, these
      results indicate a delayed and, even in the third year after the index procedure,
      continued restenotic process after beta irradiation of in-stent restenotic
      lesions.

PMID- 16275187
TI  - Impact of asymmetric stent expansion on neointimal hyperplasia following
      sirolimus-eluting stent implantation.
AB  - To assess whether asymmetric stent expansion affects suppression of neointimal
      hyperplasia after sirolimus-eluting stent implantation, 64 patients in the
      SIRolImUS-coated Bx Velocity stent trial who underwent single 18-mm stent
      implantation and 3-dimensional intravascular ultrasonography at 8-month follow-up
      were enrolled. To assess the longitudinal stent asymmetric expansion, 2 cross
      sections with a maximal/minimal stent area were chosen in each patient. To assess
      for tomographic stent asymmetric expansion, stent eccentricity was determined by
      dividing the minimum stent diameter by the maximum stent diameter. At the 2 cross
      sections with a maximal/minimal stent area, a sirolimus-eluting stent reduced
      neointimal hyperplasia significantly with no interaction between the treatment
      and stent areas. A sirolimus-eluting stent also significantly reduced neointimal
      hyperplasia in the concentric and eccentric stent groups.

PMID- 16275188
TI  - Early mobilization after percutaneous catheterization and vascular closure with a
      novel device (Star-Close).
AB  - Arteriotomy closure devices used to obtain hemostasis at the end of cardiac
      catheterization represent a valid alternative to manual compression. We are the
      first to report on a series of 60 patients in whom a novel system was used, Star
      Close, which obtains vessel closure by deployment of a clip at the puncture site.
      Subsequent early (2 hours) mobilization was obtained in 55 patients (92%).
      Unsuccessful device deployment occurred in 5 patients. We conclude that Star
      Close is a novel arteriotomy closure device that, in selected patients, is safe
      and allows early deambulation after diagnostic cardiac catheterization.

PMID- 16275189
TI  - Improvement in microvascular reflow and reduction of infarct size with adenosine
      in patients undergoing primary coronary stenting.
AB  - The aim of this study was to use myocardial contrast echocardiography to evaluate
      the effect of intravenous adenosine on microvascular reflow in patients with
      acute myocardial infarction who underwent primary coronary stenting (PCS). Thirty
      patients who underwent primary PCS for acute myocardial infarction were
      randomized to intravenous adenosine (50 to 70 mug/kg/min) or vehicle for 3 hours.
      Myocardial contrast echocardiography was performed before and sequentially after
      PCS to determine the risk area during coronary occlusion and infarct size. The
      risk area was similar in the adenosine- and placebo-treated patients. The infarct
      size as a ratio to the risk area was smaller in patients treated with adenosine
      when measured at 3 to 5 days (0.37 +/- 0.29 vs 0.68 +/- 0.25, p <0.01) and at 4
      weeks (0.34 +/- 0.26 vs 0.60 +/- 0.21, p <0.01) after PCS. This effect was
      greatest when patency was achieved <4 hours after symptom onset (0.18 +/- 0.18 vs
      0.74 +/- 0.31, p <0.05), with little effect after 4 hours. The relative
      microvascular blood volume in the risk area at 4 weeks was higher in patients
      receiving adenosine than in those receiving placebo (0.73 +/- 0.22 vs 0.57 +/-
      0.20, p <0.01), and was highest when patency was achieved in <4 hours. In
      conclusion, the adjunctive use of intravenous adenosine after PCS reduces the
      infarct size relative to the risk area. This beneficial effect occurs primarily
      in those undergoing early intervention.

PMID- 16275190
TI  - Comparison of outcomes in patients undergoing coronary bypass of patent versus
      restenosed bare metal stented coronary arteries.
AB  - It is unclear whether bypass of a patent stented artery affects clinical
      outcomes. We sought to compare the survival of patients who, as part of
      multisystem coronary artery bypass grafting, underwent revascularization of
      arteries with patent stents (<50% stenosis) or in-stent restenosis (>50% diameter
      stenosis). Of 550 consecutive patients with previously placed stents who
      underwent coronary artery bypass grafting from May 1995 to October 2003, we
      studied 399 who had only 1 stented vessel bypassed at surgery. Of these, 128 had
      coronary bypass to an artery with a patent stent and 271 had bypass to an artery
      with in-stent restenosis. Nonparametric survival estimates were obtained using
      the Kaplan-Meier method. A propensity-adjusted multivariate hazard model of group
      differences was generated using variables identified by bootstrap bagging. The
      unadjusted survival rate at 1 month, 1 year, and 5 years was 99.7%, 97.3%, and
      89.1%, respectively, for the patent stent group and 96.6%, 93.9%, and 86.2%,
      respectively, for the in-stent restenosis group, a result of high early risk in
      the latter group. After adjusting for clinical variables, neither stent patency
      (p = 0.9) nor interval (p = 0.3) from stent placement was a risk factor, although
      advanced age, increased blood urea nitrogen, and preoperative atrial fibrillation
      were associated with poorer survival. In conclusion, survival after bypassing a
      patent stented coronary artery is comparable to that after bypassing a stented
      restenotic coronary artery.

PMID- 16275191
TI  - Effect of atrial fibrillation pattern on survival in a community-based cohort.
AB  - The clinical presentation of recurrent atrial fibrillation (AF) has been
      categorized into 3 general patterns: paroxysmal, persistent, and permanent AF.
      This community-based cohort study characterized the effect of the AF pattern on
      survival. Community residents in Olmsted County, Minnesota, with
      electrocardiographically proven new-onset AF during 1996 and 1997 were
      retrospectively identified and prospectively followed. Observed survival was
      estimated using the Kaplan-Meier method and compared with the expected survival.
      Log-rank tests were used for group comparisons. The association between the
      baseline variables and mortality was assessed using Cox proportional hazards
      models. Of 270 patients (mean +/- SD age 73 +/- 14 years; 148 men [55%]), 143 had
      paroxysmal AF, 40 had persistent AF, and 87 had permanent AF. The cohort's
      observed survival was significantly worse than expected (p <0.001). The factors
      associated with increased mortality included older age, concomitant heart
      failure, and concomitant chronic obstructive pulmonary disease (all p <0.001).
      Permanent AF was associated with higher mortality than paroxysmal AF (hazard
      ratio 1.6, 95% confidence interval 1.1 to 2.3). Persistent AF was associated with
      better survival (hazard ratio 0.3, 95% confidence interval 0.1 to 0.8). In
      conclusion, survival among patients with persistent AF was significantly better
      than that among patients with paroxysmal AF or permanent AF. The ability to
      maintain sinus rhythm may be associated with better survival.

PMID- 16275192
TI  - Use of autonomic maneuvers to probe phenotype/genotype discordance in congenital
      long QT syndrome.
AB  - Patients with congenital long QT syndrome due to potassium channel mutations
      (LQT1 and LQT2) may elude diagnosis due to normal electrocardiographic findings
      at rest, yet remain at risk of sudden death during bradycardia or sympathetic
      stimulation. To test the hypothesis that autonomic maneuvers can unmask long QT
      syndrome in genetically abnormal subjects with a normal phenotype (QTc < or =450
      ms), we exposed 13 controls (33 +/- 9 years; 5 men), 5 patients with LQT1 (32 +/-
      12 years; 3 men), and 5 patients with LQT2 (30 +/- 11 years; 5 men) to
      phenylephrine bolus, exercise, and epinephrine infusion. The QT interval was
      measured at baseline and after each intervention. A substantial overlap was found
      in QTc among the groups at baseline and after phenylephrine. In contrast, QTc was
      significantly and consistently longer in subjects with LQT1 compared with
      controls during and after exercise (492 +/- 40 vs 407 +/- 14 ms, p <0.0001, at
      peak exercise; 498 +/- 30 vs 399 +/- 20 ms, p <0.0001, at 1 minute into recovery)
      or epinephrine (623 +/- 51 vs 499 +/- 51 ms, p <0.001, at peak epinephrine; 604
      +/- 36 vs 507 +/- 54 ms, p <0.01, at 1 minute into recovery) but not in subjects
      with LQT2. In conclusion, sympathetic stimulation can reveal the LQT1 phenotype
      even in subjects with normal baseline electrocardiographic findings.

PMID- 16275193
TI  - Relation of clinical presentation of syncope to the age of patients.
AB  - The aim of the study was to evaluate the effect of patient age on the clinical
      presentation of syncope and to establish the diagnostic value of clinical history
      in older patients. A total of 485 consecutive patients with unexplained syncope
      referred to secondary and tertiary hospitals were divided into 2 predefined age
      groups: 224 patients <65 years and 261 patients > or =65 years. The diagnostic
      criteria for the cause of syncope were developed before the beginning of the
      study. The clinical features of syncope were analyzed using a standard 46-item
      form. A cardiac cause of syncope was established in 27 younger (12%) and 89 older
      (34%) patients. A neurally mediated cause was established in 154 younger (68%)
      and 142 older (54%) patients. In patients > or =65 years, the clinical features
      of cardiac and neurally mediated syncope were very similar. The diagnosis of the
      cause of syncope was possible on the basis of the history alone in 26% younger
      and 5% older patients (p <0.0001). Myoclonic movements, effort syncope, and
      supine position during loss of consciousness were the most specific (97%, 99%,
      and 99%, respectively) diagnostic criteria for a cardiac cause of syncope in
      older patients, but, all together, they accounted for only 14% of patients. In
      conclusion, compared with younger patients, the medical history has a limited
      value in the diagnosis of the cause of syncope in older patients. The specificity
      of some features is high but these can be observed in only a minority of
      patients.

PMID- 16275194
TI  - Effect of sildenafil on cardiac performance in patients with heart failure.
AB  - Sildenafil is rarely used in patients with heart failure despite a high
      prevalence of erectile dysfunction, and the theoretic possibility that by
      increasing nitric oxide availability, it may improve left ventricular (LV) load
      and performance. This study aimed to determine the peak effects of sildenafil on
      LV load and performance in patients with heart failure caused by systolic LV
      dysfunction. Twenty patients with controlled LV failure and ejection fractions
      <35% received sildenafil 50 mg or a matching placebo when not receiving regular
      medication for > or =12 hours, in a randomized, placebo-controlled, double-blind,
      2-way crossover fashion. Cardiac output was measured by Doppler echocardiography.
      The aortic pressure waveform was determined using generalized transfer function
      from radial artery applanation tonometry. Aortic and femoral arterial stiffness
      was determined as carotid-femoral and femoral-pedal pulse-wave velocity (PWV);
      wave reflection was measured as an augmentation index (AIx). Cardiac index
      increased significantly (by 0.37 L/min.m(2), p <0.0001), with the peak effect 60
      minutes after sildenafil administration. Compared with the baseline value, total
      systemic resistance showed a reduction of 479 dynes.s.cm(-5) (p <0.0001). Aortic
      and lower limb PWV decreased significantly (by 0.89 and 1.14 m/s, respectively, p
      <0.0001 for both), as did AIx (by 3.6% absolute, p <0.0001); these remained
      significant after adjustment for mean pressure and heart rate changes. In
      conclusion, sildenafil improves cardiac performance because of a decrease in LV
      load, which is caused by decreases in peripheral resistance, in aortic and large
      artery stiffness, and in wave reflection from peripheral sites. This can explain
      the increase in cardiac output and in exercise capacity with sildenafil in
      patients with heart failure.

PMID- 16275195
TI  - Aortic root growth in men and women with the Marfan's syndrome.
AB  - The leading cause of premature death in patients with Marfan's syndrome (MS) is
      type A aortic dissection or rupture due to progressive aortic root dilation. The
      aim of this study was to analyze aortic root growth in 113 men and 108 women with
      MS. All patients were prospectively followed with serial echocardiograms of the
      native aortic root. At baseline, women had on average a 5-mm smaller aortic root
      diameter adjusted for age than men. Average aortic root growth was 0.42 mm/year
      (SE 0.05) in men and 0.38 mm/year (SE 0.04) in women. On the basis of aortic root
      growth rates, the men and women could be divided into 2 normally distributed
      subgroups: fast and slow growers. Approximately 1 in 7 men (1.5 mm/year, SE 0.5)
      and approximately 1 in 9 women (1.8 mm/year, SE 0.3) had fast-growing aortic root
      diameters. Significantly more type A dissections (25% vs 4%, p <0.001) were
      observed in fast growers than in slow growers; this was found in men and women.
      Type A dissections were observed in 4 men and 9 women. By reducing the cut-off
      value by 5 mm for elective aortic root replacement in women, type A dissections
      could have been prevented in 3 women. In conclusion, guidelines should take
      gender differences into account, and therefore, the investigators propose
      reducing the threshold for elective aortic root replacement in women with MS by 5
      mm.

PMID- 16275196
TI  - Usefulness of an elevated B-type natriuretic peptide in predicting survival in
      patients with aortic stenosis treated without surgery.
AB  - Patients with aortic stenosis (AS) may remain asymptomatic with good prognoses
      for many years but have poor prognoses once they develop symptoms. Because the
      presence of symptoms is subjective, B-type natriuretic peptide (BNP) may provide
      a more objective indication of the prognoses of patients with AS. We evaluated
      124 patients with AS (valve area <1.2 cm(2)) with clinical evaluation, Doppler
      echocardiography, and BNP assessment and obtained up to 2 years of follow-up
      without valve replacement. Patients with syncope, angina, and/or heart failure
      were considered to have symptoms. The 24 patients without symptoms had lower BNP
      levels (187 +/- 193 pg/ml) than the 100 patients with symptoms (930 +/- 928
      pg/ml, p <0.001). BNP indicated symptom status, with an area under the receiver
      operating characteristic curve of 0.87 (p <0.001). The optimal discrimination of
      symptoms occurred with BNP >190 pg/ml. Survival was significantly influenced by
      the presence of symptoms (relative risk [RR] 7.5, p <0.01) and BNP tertile (RR
      2.9, p <0.001). The 1-year mortality rate without surgery was 6% for BNP <296
      pg/ml, 34% for BNP 296 to 819 pg/ml, and 60% for BNP >819 pg/ml. No patients with
      BNP <100 pg/ml died. The combination of BNP and symptoms provided a better
      prediction of survival than symptoms alone (chi-square 13.6, p <0.001). BNP
      significantly (RR 2.8, p <0.01) influenced survival after correction for other
      univariate predictors (coronary artery disease, symptoms, functional class,
      ejection fraction, and aortic valve area). In conclusion, elevated BNP indicates
      progressively worse survival in patients with AS treated medically. Thus, the
      measurement of BNP supplements the evaluation of symptoms in determining the
      prognoses of patients with AS.

PMID- 16275197
TI  - Comparison of levels of matrix metalloproteinase-2 and -3 in patients with
      ischemic cardiomyopathy versus nonischemic cardiomyopathy.
AB  - It has been reported that circulating matrix metalloproteinase (MMP) levels are
      upregulated in patients with chronic heart failure. However, experimental studies
      indicate that differences in the profiles of MMPs and tissue inhibitors of
      metalloproteinase (TIMPs) may exist in ischemic compared with nonischemic
      cardiomyopathy. This study examined whether circulating levels of MMPs and TIMP-1
      are related to the pathogenesis of heart failure. Circulating levels of MMP-2,
      MMP-3, and TIMP-1 were assessed in 52 patients with compensated end-stage chronic
      heart failure, including 26 patients (mean 64 +/- 7 years; 10 men) with ischemic
      cardiomyopathy (IC) and 26 (mean age 66 +/- 6 years; 14 men) with idiopathic
      dilated cardiomyopathy (IDC). Serum MMP-2 (p <0.001) and MMP-3 (p <0.001) levels
      were higher in patients with IDC than in those with IC. Serum TIMP-1 levels were
      lower in patients with IDC (p = 0.011) than in those with IC. This study shows
      that in patients with compensated end-stage chronic heart failure, circulating
      levels of MMP-2, MMP-3, and TIMP-1 are associated with the pathogenesis of heart
      failure.

PMID- 16275198
TI  - Usefulness of electron beam computed tomography for diagnosis of an anomalous
      origin of a coronary artery from the opposite sinus.
AB  - The ectopic origination of a coronary artery from the opposite sinus is a rare
      condition, often discovered as an incidental finding during invasive catheter
      angiography performed for the evaluation of atherosclerotic coronary artery
      disease. Although most patients lack hemodynamic significance, a small fraction
      of these anomalies have been associated with sudden cardiac death and ischemic
      complications. The exact anatomic definition of the anomalous coronary artery and
      its course, especially in relation to the ascending aorta and the pulmonary
      trunk, is therefore crucial for every imaging modality that attempts coronary
      artery visualization. To underline the potential of 3-dimensional electron-beam
      computed tomography as an important complement to invasive angiography in the
      delineation of anomalous coronary arteries, this study focused on the potentially
      malignant ectopic contralateral origination of a coronary artery.

PMID- 16275199
TI  - Comparative accuracy of color M-mode and tissue Doppler echocardiography in the
      emergency diagnosis of congestive heart failure in chronic hypertensive patients
      with normal left ventricular ejection fraction.
AB  - The accuracy of the tissue Doppler E/Ea and color M-mode Doppler E/Vp indexes in
      diagnosing congestive heart failure (HF) was investigated in 20 chronic
      hypertensive patients with acute dyspnea and normal left ventricular ejection
      fractions who met Vasan's criteria for definite diastolic HF, compared with 20
      gender- and age-matched hypertensive patients with noncardiac cause of acute
      dyspnea. The E/Ea ratio appeared to be more reproducible (variability 4% to 9% vs
      6 to 14%) and more precise (sensitivity 77.8%, specificity 100%, and accuracy
      89.5% for the optimal cutoff of 11 vs sensitivity 73.7%, specificity 75%, and
      accuracy 74.3% for the optimal cutoff of 1.5) than the E/Vp ratio in this
      clinical setting.

PMID- 16275200
TI  - The negative prognostic synergism of anemia and heart disease in female nursing
      home residents.
AB  - This study assessed functional and cognitive status, hemoglobin, serum
      creatinine, and heart disease from chart reviews in 441 female nursing home
      residents (mean age 86.8 +/- 7.5 years) and correlated the findings with 1-year
      survival. Independent predictors of outcome were older age (hazard ratio [HR]
      1.76, 95% confidence interval [CI] 1.13 to 2.73), Barthel index (HR 0.31, 95% CI
      0.15 to 0.62), and the combined presence of anemia (hemoglobin < or =11 g/dl) and
      heart disease (HR 3.50, 95% CI 1.50 to 7.47). Survival rates were 92% in the
      reference group with neither anemia nor heart disease, 91% in anemic subjects
      without heart disease, 87% in nonanemic patients with heart disease, and 72% in
      women with the 2 conditions (p <0.001). Anemia is highly prevalent in this
      population and when present in subjects with heart disease determines a threefold
      increase in mortality risk.

PMID- 16275201
TI  - Severe ataxia caused by amiodarone.
AB  - Neurologic toxicity is an infrequently reported and under-recognized consequence
      of amiodarone, symptoms of which may include tremor, peripheral sensorimotor
      neuropathy, proximal weakness, and ataxia. The investigators report the rapid and
      complete remission of 4 months of progressively debilitating ataxia with the
      discontinuation of small-dose amiodarone in an elderly woman with hypertrophic
      obstructive cardiomyopathy and paroxysmal atrial fibrillation. Despite the long
      half-life of amiodarone, her symptoms began to reduce after several days, and she
      was walking without assistance within 1 week. Wider recognition of this syndrome
      may avoid unnecessary and lengthy diagnostic evaluation and promote earlier
      neurologic recovery.

PMID- 16275202
TI  - Managing patients with high blood pressure before the introduction of
      antihypertensive drugs.

PMID- 16275203
TI  - Comments in response to "Analysis of risk of bleeding complications after
      different doses of aspirin in 192,036 patients enrolled in 31 randomized
      controlled trials".

PMID- 16275204
TI  - Statin comparisons in controlled clinical trials.

PMID- 16275205
TI  - Myocardial infarction and hyperglycemia.

PMID- 16275206
TI  - Bipolar family history of the hypomanic symptoms and dimensions of mixed
      depression.
AB  - BACKGROUND: There are no data on the bipolar family history (BPFH) of the
      hypomanic symptoms and dimensions of mixed depression (defined as a depression
      plus concurrent hypomanic symptoms). These data may be important for the genetics
      of mixed depression. The study aim was to investigate the BPFH of the hypomanic
      symptoms of mixed depression. METHODS: Consecutive 243 bipolar II disorder (BP
      II) and 189 major depressive disorder (MDD) outpatients, presenting for treatment
      of a major depressive episode (MDE), were interviewed using the Structured
      Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family
      History Screen. Mixed depression was defined as an MDE plus 3 or more intra-MDE
      hypomanic symptoms (following a definition validated by Akiskal and Benazzi [J
      Affect Disord 2003;73:113-22]). RESULTS: Major depressive episode with BPFH vs
      MDE without BPFH had significantly more BP II, lower age of onset, more MDE
      recurrences, more atypical depressions, more mixed depressions, and more intra
      MDE hypomanic symptoms (irritability, racing/crowded thoughts, psychomotor
      agitation, more talkativeness, distractibility). Factor analysis of intra-MDE
      hypomanic symptoms found 2 factors (dimensions): one factor including psychomotor
      agitation and more talkativeness, and one factor including racing/crowded
      thoughts, irritability, and distractibility. Logistic regression showed that
      mixed depression was more strongly associated with BPFH than hypomanic symptoms
      and dimensions. There was a dose-response relationship between number of intra
      MDE hypomanic symptoms and BPFH loading (marked increase at n = 3) in the entire
      BP II and MDD sample. CONCLUSIONS: Findings showed that hypomanic symptoms were
      more common in the MDE with BPFH of BP II and of MDD, suggesting that a bipolar
      vulnerability may be required for mixed depression. Mixed depression was more
      strongly associated with BPFH than hypomanic symptoms and dimensions, suggesting
      that it could be the focus of future FH studies.

PMID- 16275207
TI  - The AUDIT-C: screening for alcohol use disorders and risk drinking in the
      presence of other psychiatric disorders.
AB  - This article examines the performance of the AUDIT-C, as embedded in a large
      national survey, as a screener for alcohol use disorders (AUDs) and risk drinking
      among individuals with past-year psychopathology. The analysis is based on data
      collected in personal interviews from a representative population sample of US
      adults. The study population consisted of past-year drinkers with any past-year
      mood disorder (n = 2818), any past-year anxiety disorder (n = 3173), or any
      personality disorder (n = 4389). Screening performance was evaluated by means of
      sensitivity, specificity, and areas under receiver operating characteristic
      curves (AUCs). The AUCs for the AUDIT-C were from 0.888 to 0.893 for alcohol
      dependence, from 0.864 to 0.876 for any AUD, and from 0.941 to 0.951 for any AUD
      or risk drinking-all on a par with those observed in the general population.
      Among men, cut points of either > or =5 or > or =6 points (the former favoring
      sensitivity and the latter favoring specificity) were optimal for detecting
      dependence, and cut points of > or =5 points were optimal for any AUD and for any
      AUD or risk drinking. Among women, a cut point of > or =4 points was optimal for
      the outcomes of both alcohol dependence and any AUD, whereas a cut point of > or
      =3 points was preferable for detecting any AUD or risk drinking.

PMID- 16275208
TI  - Clinical use of the Hamilton Depression Rating Scale: is increased efficiency
      possible? A post hoc comparison of Hamilton Depression Rating Scale, Maier and
      Bech subscales, Clinical Global Impression, and Symptom Checklist-90 scores.
AB  - BACKGROUND: The 17-item Hamilton Depression Rating Scale (HDRS) is used as a semi
      gold standard in research. In treatment guidelines, the HDRS measurements serve
      to determine response and remission and guide clinical decision making for
      nonresponders. However, its use in clinical practice is limited, possibly because
      the HDRS is time consuming. In addition, the multidimensional HDRS is criticized
      for not measuring a unidimensional aspect as depression severity. The Maier and
      the Bech, two 6-item severity subscales extracted from the HDRS, are relatively
      unknown. This paper investigates whether the measurements obtained with these
      subscales are comparable with the original HDRS measurements. METHODS: Data from
      2 randomized controlled trials in 482 male and female patients, diagnosed with a
      major depression (with or without dysthymia) according to Diagnostic and
      Statistical Manual of Mental Disorders, Revised Third Edition, of whom 219
      participated in the trials, were reanalyzed. A standardized stepwise
      psychopharmacological treatment was compared with a combination of
      pharmacotherapy with Short Psychodynamic Supportive Psychotherapy in a
      psychiatric outpatient department. Outcome measures were internal consistency and
      concurrent validity of HDRS, Maier, Bech, Clinical Global Impression scales, and
      Symptom Checklist depression subscale. Effect sizes of HDRS, Maier, and Bech were
      used to compare measured treatment effects for the randomized subjects
      participating in the trials. Item Response Theory was used to obtain conversion
      tables for the HDRS, Maier, Bech, and Symptom Checklist depression subscale.
      RESULTS: We found moderate internal consistency (Cronbach alpha approximately 0.6
      0.7) and high correlations of the Maier and Bech subscales with overall HDRS
      scores. Overall, there were no clinically relevant differences in effect sizes
      between Maier, Bech, and HDRS, although some differences were statistically
      significant. Receiver operating characteristic curves showed no difference
      between Maier and Bech to define remission but showed the Clinical Global
      Impression ratings to be unreliable. A cutoff < or =4 corresponded with an HDRS <
      or =7 criterion in both subscales. CONCLUSION: In clinical practice, both Maier
      and Bech scales can be used as equivalents of the HDRS, but will be more
      efficient.

PMID- 16275209
TI  - Increased personality disorders and Axis I comorbidity in atypical depression.
AB  - OBJECTIVE: Comparison of patients with and without atypical depression on
      comorbid Axis I and I disorders to determine whether atypical depression is
      associated with a higher comorbidity. METHOD: Twenty-nine major depressive
      disorder patients with and without atypical depression were compared on clinical
      measures using multiple regression analyses. RESULTS: Atypical depression
      predicted the presence of comorbid Axis I (100% vs 33%), Axis II (90% vs 35%),
      and both Axis I and II (65% vs 8.14%) disorders. Personality disorders did not
      mediate the relationship between atypical depression and Axis I comorbidity.
      CONCLUSIONS: The high prevalence of Axis I and II comorbidity in major depression
      may be explained, at least in part, by the presence of atypical depression. Our
      findings also suggest that the increased Axis I comorbidity observed in atypical
      depression is independent of the effects of personality disorders and is probably
      a direct effect of atypical depression subtype. Future research should confirm
      whether clinical findings associated with atypical depression are independent of
      their association with personality disorders in a larger sample of depressed
      patients and also examine treatment implications in atypical depression other
      than a preferential monoamine oxidase inhibitor responsivity.

PMID- 16275210
TI  - The impact of diagnostic criteria on the prevalence of schizophrenic subtypes.
AB  - The distribution of schizophrenic subtypes shows a high range of cross-cultural
      and historical variations. Our study aimed to investigate the effect of different
      diagnostic criteria on the prevalence of schizophrenic subtypes. A sample of 220
      consecutively admitted schizophrenic patients from 3 different psychiatric
      institutions was classified according to Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, International Statistical Classification of
      Diseases, 10th Revision, and Bleuler's and Leonhard's criteria. Especially, the
      frequency of catatonic (10%-22%) and hebephrenic (5%-20%) subtypes of
      schizophrenia varied within a broad range depending on the diagnostic system
      applied. The comparison of International Statistical Classification of Diseases,
      10th Revision and Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition with "classical" criteria (Bleuler, Leonhard) for the different
      schizophrenic subtypes showed a reduction of typical symptoms and the
      introduction of criteria of prominence during the last century. These changes
      caused 2 trajectories ("paranoidization" and "shift into residual categories")
      explaining these cross-sectional variations.

PMID- 16275211
TI  - Main determinants of Global Assessment of Functioning score in schizophrenia: a
      European multicenter study.
AB  - BACKGROUND: The Global Assessment of Functioning (GAF) scale is a measure widely
      used to assess the outcome of patients with schizophrenia. However, little is
      known about the importance of clinical and psychosocial variables in determining
      its final score. The aim of this paper is to identify which factors predict GAF
      scores of patients with schizophrenia and their variability in 5 different
      European settings. METHOD: A representative sample of 404 patients with
      schizophrenia was assessed with the GAF. A multiple regression analysis was
      performed to identify predictors of the GAF scores. RESULTS: Clinical factors are
      the main determinants of GAF score. However, the analysis also showed that social
      and functioning factors were also significantly associated with GAF scores.
      Finally, the study showed the presence of intercenter differences in the factors,
      mainly in social functioning. CONCLUSIONS: The GAF is a useful and easy-to-apply
      measure of global functioning, independent of cross-cultural differences.
      Clinical factors are the main determinants of its score, although social
      functioning variables also have a lesser effect.

PMID- 16275212
TI  - Substance abuse and related diagnoses in early psychosis.
AB  - Substance abuse seems to be common among those with early signs of evolving
      psychosis. This article seeks to determine the prevalence of substance abuse and
      substance use disorders (SUDs) and the association of abuse and SUD with
      vulnerability psychosis among a sample of first-degree relatives of schizophrenic
      patients (n = 70), help-seekers (n = 29), and control subjects (n = 34). The
      Structured Interview for Prodromal Symptoms (SIPS) 1.0 was used to define the
      vulnerability status and the Structured Clinical Interview for DSM-IV Axis I to
      diagnose the subjects. Data on various other measures, including premorbid
      adjustment, personality disorder symptoms, psychological distress, and abuse of
      substances, were collected. Those who were identified as vulnerable to psychosis
      reported significantly more lifetime alcohol abuse and had more commonly an SUD
      than controls. Substance use disorder, as well as alcohol and drug abuse,
      correlated significantly with personality disorder symptoms and current positive
      SIPS score and both types of abuse also with disorganization SIPS score. The odds
      ratio for having an SUD among those vulnerable to psychosis was 6.33 (95%
      confidence interval, 1.77-22.73). Early psychosis and substance abuse frequently
      occur together.

PMID- 16275213
TI  - Quality of life in obsessive-compulsive disorder before and after treatment.
AB  - BACKGROUND: The assessment of Quality of Life (QoL) is an important tool for
      elucidating target symptoms that are particularly bothersome to patients. The
      present study was designed to explore predictors of decreased QoL in obsessive
      compulsive disorder (OCD) patients and to explore which aspects of QoL are most
      affected in OCD. Furthermore, the study investigated changes in QoL after
      treatment and the association between QoL change scores with symptomatic outcome.
      In line with prior research, it was expected that low QoL in OCD patients would
      be most pronounced for the emotional and social aspects of the construct.
      METHODS: Seventy-nine OCD patients were initially recruited. Patients were
      assessed with the SF-36 both before and after treatment. Norm values were derived
      from the general population to characterize status of impairment. OCD patients
      were contrasted with published SF-36 scores from 2 OCD samples as well as a newly
      recruited psychiatric and healthy control sample. RESULTS: Correlations with QoL
      were most pronounced for depression severity and number of OCD symptoms. Apart
      from low social and emotional QoL in the majority of patients, a large subgroup
      also reported lower physical well-being. Decreased scores on this subscale were
      mainly associated with length of illness, depression, and number of compulsions.
      Overall, QoL was significantly improved in therapy responders relative to
      nonresponders. CONCLUSIONS: The results largely correspond to previous findings
      showing that OCD patients share severely compromised well-being. Somewhat
      unexpected from previous research, QoL deficits were not restricted to emotional
      and social aspects of QoL but extended to somatic domains. The present results
      suggest that clinicians should thoroughly explore for depression as well as
      physical impairments in OCD patients, which, when present, may be additionally
      targeted to achieve comprehensive treatment success.

PMID- 16275215
TI  - Relationship of the Wender Utah Rating Scale to objective measures of attention.
AB  - The Wender Utah Rating Scale (WURS) is a 25-item self-report questionnaire for
      the retrospective assessment of childhood attention-deficit hyperactivity
      disorder (ADHD) symptoms; high scores indicate greater symptoms. The current
      study used 35 male Veterans Affairs outpatients to determine if WURS scores were
      associated with objective measures of current attentional functioning, including
      the Trail Making Test, Gordon Diagnostic System, Wechsler Adult Intelligence
      Scale-Revised digit span and digit symbol subtests, and Wechsler Memory Scale
      Revised mental control subtest. Participants included both adults diagnosed with
      ADHD (n = 14) and non-ADHD adults (n = 21). After Bonferroni correction, Pearson
      product moment correlation coefficients revealed that greater symptoms on the
      WURS were associated with poorer digit symbol performance (r = -0.69, P < .05).
      To determine which indices best predicted WURS scores, scores on attention tests
      and demographic variables were entered into a stepwise multiple regression
      analysis. Digit symbol performance was the only significant predictor of WURS
      scores (R(2) = 0.59, P < .01). Thus, poor performance on a sensitive, but
      nonspecific, measure of attention with executive function, response speed, and
      visuomotor coordination components was related to greater self-report of
      childhood ADHD symptoms.

PMID- 16275214
TI  - Cardiovascular disease in relation to weight in deceased persons with
      schizophrenia.
AB  - This study evaluated body mass index, body surface area, subcutaneous fat tissue,
      and coronary atherosclerosis by autopsy reports for people with schizophrenia who
      were deceased to evaluate the presence of cardiac atherosclerosis and its
      association with body weight. Included in the study were autopsy reports for 134
      people with schizophrenia and 134 matched normal subjects who had died between
      January 1990 and December 2000 and whose family had donated brain tissue to
      Maryland Brain Collection. Cause of death due to cardiovascular disease was
      observed for 45.7% of people with schizophrenia and 42.3% of the control group (P
      = NS). Body weight, body mass index, body surface area, and subcutaneous fat were
      not significantly different between the 2 groups; however, a larger proportion of
      the schizophrenia group had high (33.3%) and low (20.9%) percentile body weight
      compared with controls (27.7% vs 10.0%). People with schizophrenia who were
      underweight had higher rates of cardiac death than the controls (37.7% vs 13%)
      (chi(2) = 5.79, P = .01); however, no difference was noted in the number of
      coronary arteries occluded. Twenty-three (48.9%) of 47 of the controls with
      abnormally high subcutaneous fat showed cardiac atherosclerosis, whereas only 15
      (33.3%) of 45 of the schizophrenia group with abnormally high subcutaneous fat
      had atherosclerosis (P = NS). Overall, the percentage of deaths due to
      cardiovascular disease was not higher in people with schizophrenia; however, in
      normal controls, cardiovascular disease appears to be related more to weight than
      in people with schizophrenia. This may be related to intrinsic metabolic
      differences associated with schizophrenia, lifestyle differences, or effects of
      antipsychotic medications. Nonetheless, our study suggests that efforts for the
      prevention of coronary atherosclerosis in schizophrenia patients should go beyond
      weight control to target multiple risk factors such as smoking, dyslipidemia, and
      cardiac side effect of antipsychotic medications.

PMID- 16275216
TI  - No evidence for verbal memory impairment in individuals putatively at risk for
      bipolar disorder.
AB  - BACKGROUND: Hypomanic temperament and rigid personality are putative risk factors
      for affective episodes and even bipolar disorder. Individuals with bipolar
      disorder exhibit neuropsychological impairments, especially memory difficulties,
      not only during mood episodes but also when they are euthymic. Such cognitive
      impairments may also constitute a risk factor for bipolar disorder. The purpose
      of the present study was to investigate the presence of memory difficulties in
      individuals with hypomanic and rigid personality traits. METHODS: Study
      participants were 6000 German students recruited from high schools, colleges, and
      vocational schools in Germany. The students completed the Hypomanic Personality
      Scale and the Rigidity subscale of the Munich Personality Test. Four groups of
      students were selected from this sample based on their scores in the Hypomanic
      Personality Scale and Rigidity subscale: individuals with (1) hypomanic
      temperament, (2) rigid temperament, or (3) hypomanic-rigid temperament and (4)
      control participants. These students (n = 153) completed the Rey-Auditory Verbal
      Learning Test, a well-established measure of verbal learning and memory, as well
      an IQ test (Leistungsprufsystem). RESULTS: Multiple regression analyses indicated
      that sex and IQ, but not temperament, predicted learning of the Auditory Verbal
      Learning Test word list, the number of words recalled at short-delayed recall,
      and recognition. LIMITATIONS: The risk for affective disorders was only defined
      by psychometric measures, and we did not control for family history of bipolar
      disorders. CONCLUSIONS: Hypomanic temperament and Rigid personality were not
      associated with verbal learning and memory. Cognitive impairment may be
      associated with repeated mood episodes rather than constituting a risk factor for
      bipolar disorder.

PMID- 16275217
TI  - Structural and functional early human development assessed by three-dimensional
      and four-dimensional sonography.
AB  - OBJECTIVE: To summarize the role of three-dimensional and four-dimensional
      ultrasound in the assessment of early human development. DESIGN: Review of
      literature. SETTING: Ultrasound research center and obstetrics and gynecology
      department in a tertiary care facility. RESULT(S): The introduction of high
      frequency transvaginal tranducers has resulted in remarkable progress in
      ultrasonographic visualization of early embryos and fetuses and the development
      of sonoembryology. Furthermore, recent introduction of three-dimensional and four
      dimensional ultrasounds combined with the transvaginal approach has produced more
      objective and accurate information on embryonal and early fetal development. For
      the first time parallel analyses of structural and functional parameters in the
      first 12 weeks of gestation become possible. CONCLUSION(S): The anatomy and
      physiology of placental and embryonic development is a field where medicine
      exerts its greatest impact on early pregnancy at present time, and it opens
      fascinating aspects of embryonic differentiation. Clinical assessment of those
      stages of growth rely heavily on three-dimensional and four-dimensional
      sonography, one of the most promising forms of noninvasive diagnostics today and
      embryological phenomenon, once matters for textbooks are now routinely recorded
      with outstanding clarity.

PMID- 16275219
TI  - In vitro fertilization is associated with an increase in major birth defects.
AB  - OBJECTIVE: To determine the risk of major birth defects in cohorts of children
      conceived through IVF or through IUI as compared with naturally conceived
      children. DESIGN: Retrospective cohort study. SETTING: Academic medical center.
      PATIENT(S): Children conceived by IVF or IUI at the University of Iowa from 1989
      through 2002, compared with a matched cohort of naturally conceived children.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Outcome data were obtained from
      Iowa state birth and fetal death certificates and from the Iowa Birth Defects
      Registry. RESULT(S): Ninety of 1,462 IVF-conceived children (6.2%) and 17 of 343
      IUI-conceived children (5.0%) had a major birth defect, compared with 369 of
      8,422 naturally conceived children (4.4%). The adjusted odds ratio of a major
      birth defect in all IVF-conceived children was 1.30 (95% confidence interval [CI]
      1.00-1.67) and 1.11 (95% CI 0.67-1.84) for IUI-conceived children. The birth
      defect rate was increased after IVF when the analysis was limited to term
      singletons. Cardiovascular and musculoskeletal defects and known birth defect
      syndromes were increased after IVF. Among IVF-conceived children, there was no
      difference in birth defect rates after intracytoplasmic sperm injection (ICSI) or
      after transfer of cryopreserved embryos. CONCLUSION(S): Infants conceived through
      IVF have a slightly higher rate of major birth defects. More birth defects are
      noted among children born to infertile couples treated with IUI, although this
      difference is not statistically significant. Larger studies of infants conceived
      by infertile couples after all types of infertility treatment are needed to
      definitively determine whether the increased risk of birth defects is secondary
      to problems inherent in the infertile couple and/or factors associated with some
      aspect of the treatment.

PMID- 16275218
TI  - Children born after assisted fertilization have an increased rate of major
      congenital anomalies.
AB  - OBJECTIVE: To study the occurrence of major congenital anomalies (CAs) among
      children born after IVF (IVF, microinjections, and frozen embryo transfers) and
      after ovulation inductions with or without insemination (other assisted
      reproductive technologies [ART]). DESIGN: Register-based study. SETTING: Data
      regarding CAs were obtained from the Register of Congenital Malformations.
      PATIENT(S): Children from IVF (n = 4,559), children from other ART (n = 4,467),
      and controls (n = 27,078, a random sample of naturally conceived children) from
      the Medical Birth Register. INTERVENTION(S): In vitro fertilization and other ART
      treatment in ordinary practice. MAIN OUTCOME MEASURE(S): Rate of major CAs.
      Children from IVF and other ART were compared with control children, both overall
      and by plurality, controlling for confounding factors by logistic regression.
      RESULT(S): For IVF children, the adjusted odds ratio (OR) was 1.3 (95% confidence
      interval [CI], 1.1-1.6). Stratifying by gender and plurality showed that the risk
      was only increased for boys, and the risk was decreased for multiple IVF girls
      (OR = 0.5, 95% CI 0.2-0.9). The crude OR of major CA for other ART children was
      1.3 (95% CI 1.1-1.5), but adjusted differences by gender and plurality were
      statistically insignificant. CONCLUSION(S): In vitro fertilization was associated
      with an increased risk for major CAs among singleton boys and a decreased risk
      among multiple girls. The risk after other ART was only slightly increased.

PMID- 16275220
TI  - Congenital anomalies and assisted reproductive technology: more of the same.
AB  - Klemetti's birth registry study is put in context of other major studies. Summary
      advice is offered to practitioners as to what they should tell parents who
      conceive with assisted reproductive technology.

PMID- 16275221
TI  - Congenital abnormalities in children born after assisted reproductive techniques:
      how much is associated with the presence of infertility and how much with its
      treatment?
AB  - Although there is increasing evidence to link couples with infertility undergoing
      all assisted reproductive technologies, particularly intracytoplasmic sperm
      injection (ICSI), and congenital abnormalities, the reasons remain unclear. Much
      evidence suggests that infertility itself might be a risk factor, and further
      long-term follow-up studies involving different possible control groups will help
      determine whether these abnormalities are directly related to treatment.

PMID- 16275222
TI  - Risk of birth defects among children conceived with assisted reproductive
      technology: providing an epidemiologic context to the data.
AB  - Studies of assisted reproductive technology (ART) and birth defects must be
      scrutinized and appropriately interpreted in the context of their limitations.
      The recent findings reported by Klemetti et al. are compelling, given the study's
      many strengths, and add to the accumulating evidence suggestive of an association
      between ART and birth defects.

PMID- 16275223
TI  - Do children born after assisted reproductive technology have a higher incidence
      of birth defects?
AB  - Recent studies seem to find a significant increase in the incidence of birth
      defects among children conceived with assisted reproductive technologies. Those
      data should lead to proper counseling of couples treated with these techniques.

PMID- 16275225
TI  - Self-correction of chromosomally abnormal embryos in culture and implications for
      stem cell production.
AB  - OBJECTIVE: To ascertain whether embryos classified by preimplantation genetic
      diagnosis (PGD) for infertility as abnormal and then plated to obtain stem cells
      would self-correct partially or totally in culture, producing disomic stem cells.
      DESIGN: Prospective study to determine the chromosome status of embryos on day 3
      and 6, as well as cultured cells derived from inner cell masses from the same
      embryos when cultured up to day 12. SETTING: Research laboratory. PATIENT(S):
      Patients undergoing PGD of aneuploidy. INTERVENTION(S): Of 142 embryos classified
      by PGD for aneuploidy as abnormal, 50 were cultured to the blastocyst stage. At
      that stage a fraction of the embryos underwent trophectoderm biopsy to reconfirm
      the PGD diagnosis. After further co-culture with feeders up to day 12, 34 embryos
      attached to the feeder cells. Of those, 24 were analyzed by fluorescence in situ
      hybridization (FISH) and the rest for the expression of Oct-4, SSEA-3, SSEA-4,
      TRA1-60, and TRA1-80. MAIN OUTCOME MEASURE(S): Disomic cells obtained from
      trisomic embryos. RESULT(S): Analysis by FISH of day-12 cultures showed that 7
      were totally normal, 6 were mostly abnormal, and 11 had experienced some
      chromosome normalization, having between 21% and 88% normal cells. Day-12 culture
      was positive for Oct-4 expression by reverse transcriptase polymerase chain
      reaction analysis and for SSEA-3, SSEA-4, TRA1-60, and TRA1-80 by
      immunocytochemistry. CONCLUSION(S): Chromosome self-normalization occurs in a
      significant proportion of chromosomally abnormal embryos, possibly because of the
      loss of a chromosome in trisomic cells after blastocyst stage. Thus chromosomally
      abnormal embryos are a potential source of disomic stem cells. Not all
      chromosomally abnormal embryos self-corrected. Abnormal stem cells that might be
      derived could be used as models to study the effect of chromosomal abnormalities
      on human development.

PMID- 16275226
TI  - Abnormal uterine bleeding and underlying hemostatic disorders: report of a
      consensus process.
AB  - An ad hoc consensus group determined that the prevalence of von Willebrand's
      disease in females with heavy menstrual bleeding is approximately 13%, but the
      severity of the disorder varies and, consequently, the overall clinical impact
      remains unknown. Consensus recommendations are presented, which include [1] a
      structured history for screening females with heavy menstrual bleeding; [2] a
      collaborative, multidisciplinary evaluation, and [3] a strategy for future basic
      science and clinical investigation.

PMID- 16275227
TI  - Disorders of hemostasis and excessive menstrual bleeding: prevalence and clinical
      impact.
AB  - The prevalence and impact of most underlying disorders of hemostasis are reviewed
      in women with excessive menstrual bleeding. The most common underlying bleeding
      disorder is von Willebrand disease, which occurs in only 1% to 2% of the general
      population but in approximately 13% of women with excessive menstrual bleeding.

PMID- 16275228
TI  - Hemostasis and menstruation: appropriate investigation for underlying disorders
      of hemostasis in women with excessive menstrual bleeding.
AB  - The evaluation of excessive menstrual bleeding carries a relatively high yield of
      discovering an underlying disorder of hemostasis in females. This review
      highlights important components in a structured history and outlines primary and
      secondary hematologic testing that should be considered in the evaluation of
      excessive menstrual bleeding.

PMID- 16275229
TI  - Management of excessive menstrual bleeding in women with hemostatic disorders.
AB  - Because there are many important considerations for managing excessive menstrual
      bleeding in women who have systemic disorders of hemostasis, a multidisciplinary
      approach is the best model for care. Specific attention to effective treatments
      is highlighted, but few studies have been performed in this population.

PMID- 16275230
TI  - Requirements for research investigations to clarify the relationships and
      management of menstrual abnormalities in women with hemostatic disorders.
AB  - This article highlights a comprehensive range of research investigations which
      are required to clarify the relationships between the symptom of excessively
      heavy menstrual bleeding and different disorders of systemic hemostasis and their
      management. The need for these investigations was stimulated by an international
      workshop involving hematologists and gynecologists with expertise and interests
      in these fields. The field was reviewed by a group of experts who systematically
      considered nomenclature, definitions, investigations, and management and
      identified areas of uncertainty, controversy, or absence of information. This
      article is an extension of those preliminary research discussions.
      Recommendations are made for a range of important research studies to define the
      nomenclature, definitions, mechanisms, clinical investigations and management of
      heavy menstrual bleeding in women with disorders of systemic hemostasis.

PMID- 16275232
TI  - Treatment of symptomatic rectovaginal endometriosis with an estrogen-progestogen
      combination versus low-dose norethindrone acetate.
AB  - OBJECTIVE: To evaluate the efficacy, safety, and tolerability of an estrogen
      progestogen combination versus low-dose norethindrone acetate in the treatment of
      persistent pain after surgery for symptomatic rectovaginal endometriosis. DESIGN:
      Randomized controlled trial. SETTING: Academic center. PATIENT(S): Ninety women
      with recurrent moderate or severe pelvic pain after unsuccessful conservative
      surgery for symptomatic rectovaginal endometriosis. INTERVENTION(S): Twelve
      month, continuous treatment with oral ethinyl E2, 0.01 mg, plus cyproterone
      acetate, 3 mg/day, or norethindrone acetate, 2.5 mg/day. MAIN OUTCOME MEASURE(S):
      Degree of satisfaction with therapy. RESULT(S): Seven women in the ethinyl E2
      plus cyproterone acetate arm and five in the norethindrone acetate arm withdrew
      because of side effects (n=5), treatment inefficacy (n=6), or loss to follow-up
      (n=1). At 12 months, dysmenorrhea, deep dyspareunia, nonmenstrual pelvic pain,
      and dyschezia scores were substantially reduced without major between-group
      differences. Both regimens induced minor unfavorable variations in the serum
      lipid profile. According to an intention-to-treat analysis, 28 (62%) out of 45
      patients in the ethinyl E2 plus cyproterone acetate group and 33 (73%) out of 45
      in the norethindrone acetate group were satisfied with the treatment received.
      CONCLUSION(S): Low-dose norethindrone acetate could be considered an effective,
      tolerable, and inexpensive first-choice medical alternative to repeat surgery for
      treating symptomatic rectovaginal endometriotic lesions in patients who do not
      seek conception.

PMID- 16275231
TI  - Association of endometriosis with body size and figure.
AB  - OBJECTIVE: To determine whether body size and perceived figure, both current and
      historical, are associated with a diagnosis of endometriosis on laparoscopy.
      DESIGN: Cohort study of consecutively identified patients undergoing laparoscopy
      for tubal sterilization or as a diagnostic procedure. SETTING: Two university
      affiliated hospitals. PATIENT(S): A cohort of 84 women aged 18-40 years.
      Endometriosis was visualized in 32 cases; 52 women (controls) had no visualized
      endometriosis, including 22 undergoing tubal sterilization and 30 with other
      gynecologic pathology. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Body mass
      index (BMI, kg/m2) from self-report and perception of body figure were compared
      for their ability to predict case status (diagnosed endometriosis), using
      logistic regression models. Longitudinal trends in BMI based on perceived figure
      at 5-year intervals from age 15 years were compared using mixed linear models.
      RESULT(S): Based on self-report, women diagnosed with endometriosis were taller,
      thinner, and had a significantly lower BMI. In this series, cases were more
      likely to be late maturers (menarche at > or = 14 y) and late to initiate sexual
      activity (> or = 21 y), and they were less likely to be gravid, parous, and a
      current smoker. Adjusting for age (in years), being tall (height > or = 68 in),
      and parity (yes vs. no), a higher current BMI was statistically protective for a
      diagnosis of endometriosis, regardless of whether BMI was determined by self
      report (adjusted odds ratio [AOR] = 0.88, 95% confidence interval [CI] 0.79-0.99)
      or from perceived figure (AOR = 0.86, 95% CI 0.75-0.99). For every unit increase
      in BMI (kg/m2), there was an approximate 12%-14% decrease in the likelihood of
      being diagnosed with endometriosis. In an adjusted repeated measures model, BMI
      was 21.3 +/- 0.6 kg/m2 (estimate +/- SE) for women with endometriosis, compared
      with 23.2 +/- 0.4 kg/m2 for the controls, a difference over all ages of -1.9 +/-
      0.8 kg/m2. This is a consistent difference of about 10 lb at every age, assuming
      an average height of about 64.5 in. CONCLUSION(S): In a laparoscopy cohort, women
      diagnosed with endometriosis were found to have a lower BMI (leaner body
      habitus), both at the time of diagnosis and historically. That women diagnosed
      with endometriosis may have a consistently lean physique during adolescence and
      young adulthood lends support to the suggestion of there being an in utero or
      early childhood origin for endometriosis.

PMID- 16275233
TI  - Quantitative DNA perturbations of p53 in endometriosis: analysis of American and
      Icelandic cases.
AB  - OBJECTIVE: To investigate quantitative aberrations involving p53 copy numbers in
      eutopic endometrial and endometriotic tissue from two populations. DESIGN:
      Comparative analysis of normal and diseased tissue. SETTING: Tissue specimens
      collected in Iceland and USA. PATIENT(S): Subjects with moderate/severe
      endometriosis (Iceland, n = 26; USA, n = 45). Paraffin-embedded tissue from 19
      matched Icelandic cases and seven unaffected controls. American cases were fresh
      surgical tissue from 17 matched cases and 28 unaffected controls. DNA isolation
      and real-time polymerase chain reaction (PCR) with TaqMan assay were performed.
      MAIN OUTCOME MEASURE(S): The frequency of p53 loss and/or gain based on
      quantitative differences for copy numbers of p53 located on chromosome (17p) and
      GAPDH on a control locus (chromosome 12p). RESULT(S): Among American cases,
      significant p53 gain (n = 13) or loss (n = 4) was observed in 17 of 21 cases. In
      Icelandic cases this was not seen to the same degree. Mean normalized p53 values
      were 3.46 and 1.16 copies per reaction, respectively. Significant differences
      were observed between normalized p53 in the control blood and affected tissue for
      the American and Icelandic cases compared to standard GAPDH control but not in
      normal Icelandic and American endometrium. CONCLUSION(S): The results continue to
      support a role for nonrandom somatic p53 locus alterations in the pathogenesis of
      late or severe-stage endometriosis. Differences between Icelandic and American
      subjects have implications for generalization of genome-wide approaches.

PMID- 16275234
TI  - Fluorescence in situ hybridization reanalysis of day-6 human blastocysts
      diagnosed with aneuploidy on day 3.
AB  - OBJECTIVE: To determine the concordance of day-6 blastocyst analysis with the day
      3 fluorescence in situ hybridization (FISH) aneuploidy diagnosis. DESIGN:
      Retrospective study. SETTING: In vitro fertilization laboratory. PATIENT(S): Six
      hundred sixty embryos were included from 94 IVF/intracytoplasmic sperm injection
      patients undergoing preimplantation genetic diagnosis. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Single blastomeres biopsied on day 3. Aneuploidy
      screening for chromosomes 13, 18, 21, X, and Y were analyzed. Left-over
      blastocysts were reanalyzed on day 6. RESULT(S): Among the 660 embryos evaluated,
      367 (55.6%) were euploid and 281 (42.6%) were aneuploid. Of the euploid embryos,
      213 embryos were transferred, 68 were frozen on day 5, and 86 were left. All 281
      aneuploid embryos were further cultured, and 55 (19.6%) progressed to
      blastocysts. When FISH reanalysis was performed, 33 of 55 blastocysts (60%) were
      confirmed aneuploid in concordance with the day-3 diagnosis. However, 22 of 55
      blastocysts (40%) were determined to be euploid. In addition, 207 aneuploid
      embryos (73.7%) arrested before day 6, as opposed to 32 of the 86 euploid embryos
      (37.2%). CONCLUSION(S): Day-3 single-cell embryo biopsy reveals that aneuploidy
      can be confirmed in 60.7% of the blastocysts on reanalysis. The majority of
      discordance is most likely due to embryo mosaicism and possibly a limited ability
      to "self-correct."

PMID- 16275235
TI  - A comparison of three downregulation approaches for poor responders undergoing in
      vitro fertilization.
AB  - OBJECTIVE: To assess the efficacy of three different GnRH agonist (GnRH-a)
      stimulation regimens to improve ovarian response in poor responders undergoing
      IVF. DESIGN: Retrospective cohort study. SETTING: Center for Reproductive Health
      at the University of Cincinnati Medical Center. PATIENT(S): Women diagnosed as
      poor responders who presented consecutively from January 1999 to January 2004.
      INTERVENTION(S): Patients underwent three different stimulation regimens during
      IVF cycles: [1] stop protocol: GnRH-a 500 microg/d administered from the
      midluteal phase to the start of menses, then gonadotropins from day 2 of cycle,
      [2] microdose flare: GnRH-a 20 microg administered twice daily with gonadotropins
      from day 2 to the day of hCG administration, or [3] regular dose flare:
      gonadotropins beginning with GnRH-a on day 2 at 1 mg/d for 3 days, followed by
      250 microg/d until the day of hCG administration. MAIN OUTCOME MEASURE(S):
      Ovarian response, implantation rates, clinical pregnancy and delivery rates.
      RESULT(S): Sixty-one IVF cycles were included in the study. None of the
      comparisons reached statistical significance; however, the microdose group
      demonstrated a trend toward a higher completed pregnancy rate. CONCLUSION(S): The
      microdose flare protocol for poor responders demonstrated a trend toward higher
      delivery rates. A larger prospective study would need to be performed to
      determine whether this trend leads to a significant finding in this patient
      population.

PMID- 16275236
TI  - Outcome of in vitro fertilization treatment in patients who electively inseminate
      a limited number of oocytes to avoid creating surplus human embryos for
      cryopreservation.
AB  - OBJECTIVE: To determine whether the outcome of IVF treatment in patients who
      electively inseminate a limited number of oocytes is comparable to that in a
      group of good-prognostic or poor-prognostic patients. DESIGN: Retrospective
      clinical study. SETTING: University-based tertiary fertility center. PATIENT(S):
      Two hundred three women under the age of 40 years. INTERVENTION(S): Patients
      undergoing their first cycle of IVF who elected to have no more than four oocytes
      inseminated (study group) or who produced only four or fewer oocytes (poor
      prognostic group) or who had excess embryos cryopreserved (good-prognostic
      group). MAIN OUTCOME MEASURE(S): Implantation rate, clinical pregnancy rate, and
      ongoing pregnancy rate. RESULT(S): There were no significant differences in the
      implantation rate for the study group when compared with the good-prognostic
      group or the poor-prognostic group. The clinical pregnancy rate (62.5% vs. 64%)
      and ongoing-pregnancy or birth rate (56.3% vs. 60.7%) were similar between the
      study group and the good-prognostic group. However, the clinical pregnancy rate
      (62.5% vs. 29.7%) and ongoing-pregnancy rate (56.3% vs. 24.3%) were higher in the
      study group compared with the poor-prognostic group. CONCLUSION(S): Inseminating
      fewer oocytes in patients who elect not to cryopreserve excess embryos does not
      adversely affect their probability of conception.

PMID- 16275237
TI  - Use of both early cleavage and day 2 mononucleation to predict embryos with high
      implantation potential in intracytoplasmic sperm injection cycles.
AB  - OBJECTIVE: To evaluate the value of early cleavage and day 2 mononucleation as
      combined parameters in predicting the implantation potential of embryos. DESIGN:
      Prospectively designed retrospective cohort analysis. SETTING: Private IVF
      center. PATIENT(S): Two hundred eighty-seven ICSI cycles were evaluated in four
      groups according to the presence of early cleavage and mononucleation in all
      (ECM), some (pECM, ECpM), or none (noECnoM) of the transfer embryos.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Embryo quality and pregnancy and
      implantation rates. RESULT(S): The cycle characteristics, embryo quality, and
      pregnancy rates were similar when all (ECM) or some (pECM and ECpM) transfer
      embryos displayed these parameters. The poorest cycle characteristics and outcome
      were observed in the absence of both parameters (noECnoM). When early cleavage
      was present, a higher implantation rate was observed when all transfer embryos
      displayed mononucleation at day 2 (ECM) than when this was the case only in some
      (ECpM). CONCLUSION(S): Combination of early cleavage and day 2 mononucleation
      improves selection of embryos with high implantation potential in ICSI cycles
      with good prognosis.

PMID- 16275238
TI  - Apoptosis in human unfertilized oocytes after intracytoplasmic sperm injection.
AB  - OBJECTIVE: To investigate the presence of programmed cell death in unfertilized
      oocytes after intracytoplasmic sperm injection (ICSI), assuming that previous
      apoptotic events could be correlated with the fertilization failure. DESIGN:
      Comparison of the rate of DNA fragmentation in human oocytes at different stages
      of maturation soon after pick-up (control) and in unfertilized oocytes after ICSI
      treatment. SETTING: In vitro fertilization (IVF) laboratory with extensive ICSI
      experience. PATIENT(S): Sixty-three patients undergoing assisted fertilization by
      ICSI. INTERVENTION(S): Terminal deoxynucleotidyl transferase-mediated digoxigenin
      dUTP nick-end labeling (TUNEL) assay and anticaspase-3 cleaved immunoassay to
      detect apoptosis in control and ICSI-treated oocytes. MAIN OUTCOME MEASURE(S):
      Differences in the percentage of oocytes demonstrating DNA fragmentation between
      control oocytes and unfertilized ICSI treated oocytes at different stages of
      maturation. RESULT(S): The DNA fragmentation, by TUNEL assay, appeared in all the
      immature control oocytes, but only 37% of mature oocytes showed DNA
      fragmentation. This DNA fragmentation was observed in 88.8% of the oocytes
      unfertilized after ICSI; furthermore, DNA fragmentation appeared as well in the
      sperm injected into the cytoplasm. CONCLUSION(S): The study has shown DNA
      fragmentation in human oocytes unfertilized after ICSI. The evidence is confirmed
      as well in control oocytes, free from in vitro culture or manipulation stress.
      Caspase-3 immunoassay suggests the presence of apoptosis. The high percentage of
      oocytes demonstrating DNA fragmentation in the unfertilized oocytes could be
      correlated with fertilization failure.

PMID- 16275239
TI  - Use of a hierarchical logistic regression model to determine the impact of war
      injuries on clinical pregnancy rates in patients undergoing intracytoplasmic
      sperm injection.
AB  - OBJECTIVE: To determine the effects of war injuries, including spinal cord
      injuries, poisoning, and other injuries, on clinical pregnancy rates in infertile
      couples undergoing intracytoplasmic sperm injection (ICSI) and to compare the
      results with infertile couples who were not victims of the war. DESIGN:
      Retrospective study. SETTING: A large, national clinic in Tehran, Iran.
      PATIENT(S): Six hundred sixty-seven couples undergoing ICSI. INTERVENTION(S):
      Database analysis. MAIN OUTCOME MEASURE(S): Ongoing clinical pregnancy.
      RESULT(S): War victims with spinal cord injuries and those who had been poisoned
      had the same pregnancy rates as did infertile couples who were not victims of the
      war. The predictive model shows that the more embryos that are transferred, the
      more the chances for clinical pregnancies; in addition, the more cycles a couple
      undergoes, the fewer are the chances for clinical pregnancy in an additional
      cycle. Finally, younger females have more chances for clinical pregnancy than do
      older ones. CONCLUSION(S): Intracytoplasmic sperm injection is an appropriate
      option for the treatment of infertile war victim couples, especially for couples
      suffering from spinal cord injuries and poisoning.

PMID- 16275240
TI  - Molecular aspects of declining sperm motility in older men.
AB  - OBJECTIVE: To investigate the molecular mechanism for declining sperm motility in
      older men. DESIGN: Retrospective and prospective study. SETTING: University-based
      andrology unit. PATIENT(S): Semen was collected from 2,111 patients and sperm
      donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Age, sperm concentration,
      ejaculate volume, sperm motility (including velocity average path, velocity
      straight line, velocity curvilinear, linearity, and lateral head displacement),
      normal sperm morphology, percentage of abnormally blue-stained flagella, and
      total and free T, FSH, and LH concentrations were analyzed. In addition, the zinc
      concentration in the seminal fluid, flagella, and the whole spermatozoa was
      measured by means of atomic absorption spectrometry. RESULT(S): Patient age
      correlated negatively with T concentration and sperm motility, including
      velocity, but positively with the percentage of abnormally stained flagella and
      the flagellar zinc. Whereas the percentage of abnormally stained flagella
      correlated negatively with motility and sperm velocity, there was a positive
      relationship with the flagellar zinc content. Flagellar zinc content was
      negatively correlated with motility. Testosterone showed a positive relationship
      with motility and sperm concentration. CONCLUSION(S): Because the epididymis is
      functionally T-dependent, our data suggest that the removal of zinc from the
      outer dense fibers during epididymal sperm maturation is affected in aging men,
      which in turn will result in decreased sperm motility.

PMID- 16275241
TI  - Cancer and cardiovascular disease after vasectomy: an epidemiological database
      study.
AB  - OBJECTIVE: To determine whether vasectomy is associated with an increased long
      term risk of cancer or cardiovascular disease. DESIGN: Analysis of database of
      linked statistical records of hospital admissions and deaths. SETTING: Health
      region in southern England. PATIENT(S): Men aged 20-59 years who were admitted to
      a hospital for vasectomy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rates
      of cancer and cardiovascular disease compared with the corresponding rates in a
      reference cohort, expressed as a rate ratio. RESULT(S): We found no elevation of
      risk, after vasectomy, of prostate cancer (rate ratio 0.74, 95% confidence
      interval [CI] 0.45-1.14) or other cancers. The rate ratio for coronary heart
      disease overall after vasectomy was 0.95 (95% CI 0.88-1.02); and the rate ratio >
      or =20 years after vasectomy was 0.98 (95% CI 0.80-1.19). CONCLUSION(S): Our
      findings add to the evidence that vasectomy is not associated with an increase in
      the long-term risk of these diseases.

PMID- 16275242
TI  - Occurrence of D-aspartic acid in human seminal plasma and spermatozoa: possible
      role in reproduction.
AB  - OBJECTIVE: To determine D-aspartic acid (D-Asp) in human seminal plasma and
      spermatozoa in fertile and infertile donors. DESIGN: Prospective observation
      study. SETTING: Department of Pathophysiology for Human Reproduction, Hospital
      "S. Luca," Salerno, Italy, and Department of Neurobiology and Comparative
      Physiology, Zoological Station "A. Dohrn," Naples, Italy. PATIENT(S): Ten
      normospermic, 10 oligoasthenoteratospermic, and 10 azoospermic (nonobstructive)
      men. INTERVENTION(S): D-aspartic acid was determined by a specific enzymatic high
      performance liquid chromatography method on purified seminal plasma and on
      isolated spermatozoa and by an immunohistochemical method using light and
      electronic microscopic techniques. MAIN OUTCOME MEASURE(S): Concentration of D
      Asp in seminal plasma and in isolated spermatozoa; subcellular localization of D
      Asp in the acrosome and nucleus. RESULT(S): The concentration of D-Asp in seminal
      plasma and in spermatozoa was significantly reduced in oligoasthenoteratospermic
      donors. In the seminal fluid of normospermic donors, D-Asp occurs at a
      concentration of 80 +/- 12 nmol/mL semen (10.4 +/- 1.5 microg/mL), whereas 26 +/-
      6 nmol/mL semen were found in oligoasthenoteratospermic donors, and 12 +/- 1.5
      nmol/mL semen were found in azoospermic donors. In spermatozoa from normospermic
      donors, D-Asp occurred at a concentration of 130 +/-15 fmol per spermatozoa (17.0
      +/- 1.96 ng per spermatozoa), vs. 60.5 +/- 5.0 fmol per spermatozoa from
      oligoasthenoteratospermic subjects. Other D-amino acids analyzed were not present
      in seminal plasma or in spermatozoa in a significant concentration compared with
      D-Asp. CONCLUSION(S): D-aspartic acid occurs in human seminal plasma and
      spermatozoa and is implicated in male fertility.

PMID- 16275243
TI  - Reduction of postoperative adhesions after laparoscopic gynecological surgery
      with Oxiplex/AP Gel: a pilot study.
AB  - OBJECTIVE: To determine whether Oxiplex/AP Gel (FzioMed, San Luis Obispo, CA) was
      safe and preliminarily effective in reducing postsurgical adhesions after adnexal
      surgery by laparoscopy. DESIGN: Prospective, multicenter, double-blind,
      randomized, U.S. Food and Drug Administration-monitored feasibility study.
      SETTING: University and private clinics. PATIENT(S): Patients undergoing
      laparoscopic surgery with pelvic adhesions, tubal occlusion, endometriosis,
      and/or dermoids were randomized to receive Oxiplex/AP Gel or no further treatment
      after surgery. INTERVENTION(S): A blinded, parallel-group design was conducted at
      six centers. Patients (aged 18-46 years) underwent laparoscopic surgery, with
      second-look surgery 6-10 weeks later. Surgeries were videotaped. Oxiplex/AP Gel
      was used to cover adnexa and adjacent tissue. MAIN OUTCOME MEASURE(S): Blinded
      reviews of videotapes were quantitated with the American Fertility Society
      adhesion score (AFS score). RESULT(S): In 18 treatment patients, surgery was
      performed on 29 adnexa. Application of Oxiplex/AP Gel required approximately 90
      seconds. In 10 control patients, surgery was performed on 18 adnexa. The mean
      baseline AFS score for each group was 8.0. At second look, treated adnexa had the
      same score (8.1), whereas in control adnexa the score increased (from 8.0 to
      11.6). Thirty-four percent of treated adnexa increased in adhesion score, in
      contrast to 67% of control adnexa. There were no device-related adverse events.
      CONCLUSION(S): In this pilot study, Oxiplex/AP Gel was safe, easy to use with
      laparoscopy, and produced a reduction in the increase of adnexal adhesion scores.

PMID- 16275244
TI  - Adhesion formation after laparoscopic excision of endometriosis and lysis of
      adhesions.
AB  - OBJECTIVE: To evaluate adhesion reformation after laparoscopic excision of
      endometriosis and adhesiolysis in women with chronic pelvic pain. DESIGN:
      Prospective clinical trial. SETTING: University hospital. PATIENT(S): Thirty
      eight women with endometriosis and chronic pelvic pain. INTERVENTION(S): A
      primary and second-look laparoscopy with adhesiolysis and excision of
      endometriotic lesions with a neodymium-yttrium argon garnet surgical laser
      technologies (SLT) contact laser. MAIN OUTCOME MEASURE(S): Adhesion formation and
      character (thin, thin and thick, or thick). Location of adhesions at a first
      laparoscopy was compared with de novo or reformation of adhesions and the
      location of adhesions at a second surgery. RESULT(S): Adhesions or adhesions
      combined with endometriotic lesions were significantly more likely to reform at
      second surgery compared with sites having only an endometriosis lesion. Thick
      adhesions were associated with a significantly increased likelihood of an
      adhesion reforming, compared with thin adhesions or thin and thick adhesions.
      Lesions or adhesions involving the ovary were more likely to be associated with
      adhesions at a subsequent surgery, compared with lesions in the adjacent ovarian
      fossa or fallopian tube. CONCLUSION(S): Most patients developed adhesions after
      radical surgical excision of endometriosis for pelvic pain. The high incidence of
      adhesion formation after surgery for endometriosis underscores the importance of
      optimizing surgical techniques to potentially reduce adhesion formation.

PMID- 16275246
TI  - Effect of metformin on the growth hormone response to growth hormone-releasing
      hormone in obese women with polycystic ovary syndrome.
AB  - OBJECTIVE: Obese women with polycystic ovary syndrome (PCOS) show a marked growth
      hormone (GH) hyporesponsiveness to several stimuli. We aimed to evaluate the
      impact of insulin metabolism on the GH secretion impairment in these subjects in
      relation to food ingestion. DESIGN: Prospective clinical study. SETTING: Academic
      research center. PATIENT(S): Nine obese women with PCOS. INTERVENTION(S):
      Metformin (1,500 mg/daily) was administered for three months. The study protocol,
      which was performed before and after therapy, included hormonal and lipid assays,
      oral glucose tolerance test (75 g), euglycemic hyperinsulinemic clamp, and growth
      hormone-releasing hormone (GHRH) test (50 microg/ev), both on fasting and after a
      standard meal. MAIN OUTCOME MEASURE(S): Growth hormone response to GHRH
      (expressed as the area under the curve) in different experimental conditions.
      RESULT(S): The preprandial GH response to GHRH was not modified by the therapy,
      whereas a significant increase (P<.05) occurred in the postprandial GH secretion,
      thus resembling the response of obese normal persons. This change was accompanied
      by a trend towards improvement, though not statistically significant, of all the
      evaluated glycoinsulinemic parameters. A significant reduction in cholesterol
      (P<.01) and androstenedione (P<.05) and an increase in sex hormone-binding
      globulin (P<.05) were also achieved. CONCLUSION(S): These data suggest that
      metformin is able to affect GH secretion in obese women with PCOS, even with
      minimal metabolic modifications.

PMID- 16275245
TI  - Pilot study investigating the age-related decline in ovarian function of
      regularly menstruating normal women.
AB  - OBJECTIVE: To use a pilot study to investigate markers of the age-related decline
      in ovarian function of regularly menstruating normal women. DESIGN: Prospective.
      SETTING: Tertiary research center. PATIENT(S): Healthy volunteers (n = 42) aged
      18 to 50 years who had regular ovulatory menstrual cycles and a prior pregnancy.
      INTERVENTION(S): A single 300-IU dose of human recombinant FSH on day 3 of the
      menstrual cycle. MAIN OUTCOME MEASURE(S): Antral follicle count by transvaginal
      ultrasound and basal and FSH-stimulated serum markers. RESULT(S): Age correlated
      most strongly with FSH-stimulated inhibin B (r = -0.660), followed by antral
      follicle count (r = -0.578), basal FSH (r = 0.509), basal Mullerian inhibiting
      substance (MIS; r = -0.468), and basal inhibin B (r = -0.358). Total antral
      follicle count correlated most strongly with basal MIS level (r = 0.642).
      CONCLUSION(S): Of the parameters tested, FSH-stimulated serum inhibin B level had
      the strongest correlation with age. Basal serum MIS level had the strongest
      correlation with total antral follicle count. We confirm a previous report that
      in normal women, the antral follicle count as determined by transvaginal
      ultrasound examination correlates better with age than do basal FSH and basal
      inhibin B levels.

PMID- 16275247
TI  - Short-term effect of transdermal estrogen on autonomic nervous modulation in
      postmenopausal women.
AB  - OBJECTIVE: To evaluate the effect of short-term transdermal estradiol-l7b on
      cardiac autonomic nervous modulation in postmenopausal women. DESIGN: Prospective
      study. SETTING: A tertiary medical center. PATIENT(S): Twenty-one postmenopausal
      women. INTERVENTION(S): Transdermal estradiol or placebo therapy for 3 weeks in
      randomized, double-blinded, crossover fashion. MAIN OUTCOME MEASURE(S): Heart
      rate variability measures in both time and frequency domains, serum biochemistry,
      and climacteric symptoms were compared among baseline, placebo and transdermal
      estrogen therapies. RESULT(S): Plasma concentration of estradiol rose
      significantly from 11.0 +/- 5.2 pg/ml to 48.2 +/- 34.0 pg/ml after transdermal
      estrogen. The standard deviation of RR-interval increased significantly from 30.3
      +/- 9.9 ms (placebo) to 31.3 +/- 7.4 ms (transdermal estrogen), and the
      coefficient of variation of RR-interval increased significantly as compared with
      the baseline session. The total power was marginally increased as compared among
      baseline, placebo, and transdermal estrogen sessions. The irritability symptom
      decreased significantly after transdermal estrogen therapy, as compared with
      baseline and placebo treatment. CONCLUSION(S): Transdermal estradiol for 3 weeks
      could significantly increase the global heart rate variability and reduce the
      irritability symptom in the postmenopausal women. Short-term transdermal estrogen
      for 3 weeks could improve cardiac autonomic nervous modulation and climacteric
      symptoms, and might have some cardioprotective effect in postmenopausal women.

PMID- 16275248
TI  - Interleukin-1 system messenger ribonucleic acid and protein expression in human
      fallopian tube may be associated with ectopic pregnancy.
AB  - OBJECTIVE: To investigate the interleukin-1 (IL-1) system mRNA and protein
      expression in human fallopian tubes with ectopic pregnancies. DESIGN: A
      controlled study. SETTING: Clinical and academic research setting in a university
      medical center. PATIENT(S): Women undergoing salpingectomy for fallopian tube
      with ectopic pregnancy and women undergoing tubal ligation. INTERVENTION(S):
      Paired segments of human fallopian tubes containing an ectopic pregnancy and
      parafallopian tube segments adjacent to the ectopic pregnancy were collected from
      five women undergoing laparoscopic salpingectomy. Segments of fallopian tubes
      from four women undergoing tubal ligation were used as control tissues.
      Quantitative competitive polymerase chain reaction (QC-PCR) and
      immunohistochemistry were performed. MAIN OUTCOME MEASURE(S): The differences of
      IL-1 system mRNA and the ratio of IL-1beta to IL-1 receptor antagonist (IL-1ra)
      in both fallopian tubes with ectopic pregnancies and normal controls were
      analyzed. RESULT(S): A complete IL-1 system mRNA and protein expression was
      identified in both fallopian tubes with ectopic pregnancies and normal controls.
      As QC-PCR demonstrated, IL-1beta mRNA expression was decreased, and IL-1ra and IL
      1 receptor type 1 were increased in fallopian tubes with ectopic pregnancies in
      comparison with normal control tubes. In para-ectopic tubes, IL-1 receptor type 1
      mRNA was statistically significantly increased in comparison with normal
      controls. There was a lower ratio of IL-1beta to IL-1ra at mRNA in fallopian
      tubes with ectopic pregnancies. CONCLUSION(S): These results suggest that an
      inappropriate ratio of IL-1beta to IL-1ra and a higher expression of its receptor
      in fallopian tubes may possibly be implicated to the implantation of an ectopic
      pregnancy in the oviduct.

PMID- 16275249
TI  - The VCUAM (Vagina Cervix Uterus Adnex-associated Malformation) classification: a
      new classification for genital malformations.
AB  - OBJECTIVE: With an incidence of up to 5% in the general population, genital
      malformations are a frequent clinical occurrence. However, using the existing
      published classifications of malformations, difficulties arise in classifying
      genital malformations appropriately. The aim of the present study was to produce
      a simple, systematic, and reproducible classification system. DESIGN: A
      systematic arrangement of genital and associated malformaltions, using a
      structure similar to that in the TNM classification of oncological tumors, was
      developed and validated. SETTING: Patients with genital malformations in a
      university hospital. PATIENT(S): Ninty-nine premenopausal patients with genital
      malformations. INTERVENTION(S): Patients were diagnosed for genital malformation
      using laparoscopy or magnetic resonance imaging. MAIN OUTCOME MEASURE(S): A new
      classification (VCUAM) is presented to evaluate patients with different genital
      malformations. RESULT(S): The external and internal female genital organs were
      divided into the following subgroups in accordance with the anatomy: vagina (V),
      cervix (C), uterus (U), and adnexa (A). Associated malformations were assigned to
      a subgroup (M) relative to each specific organ. The classification was validated
      in a group of 99 patients with genital malformations. CONCLUSION(S): The VCUAM
      classification for the first time makes it possible to reflect even complex
      malformations in a precise and individual fashion, taking associated
      malformations into account. The classification makes it easier to provide
      appropriate clinical care for the affected patients.

PMID- 16275250
TI  - A modified embryo cryopreservation method increases post-thaw survival with a
      concomitant increase in implantation.
AB  - OBJECTIVE: To achieve maximum post-thaw survival of frozen embryos. DESIGN:
      Historical controlled study. SETTING: Hospital-based fertility center.
      PATIENT(S): One hundred forty-five patients whose embryos were frozen and thawed
      according to the standard method, and 56 patients whose embryos were frozen and
      thawed according to a modified method. INTERVENTION(S): Modifications were made
      to the various steps of cryopreservation: freezing and thawing solutions, loading
      of embryos into the straws, and warming rates. MAIN OUTCOME MEASURE(S): Post-thaw
      survival, implantation, and pregnancy rates. RESULT(S): With the modified method,
      138 (93%) of the 149 embryos thawed for 56 patients survived freezing, and 79.8%
      had all their blastomeres intact, which is almost double the result obtained
      (41.8%) for patients whose embryos were thawed with the standard method. The
      implantation and pregnancy rates were also significantly higher with the modified
      method compared with the standard method. CONCLUSION(S): Greater post-thaw embryo
      survival was achieved, with a concomitant increase in implantation and pregnancy
      rates, by modifying the various steps in the standard cryopreservation
      methodology. This has important implications in IVF practice.

PMID- 16275251
TI  - Images in reproductive medicine. Disseminated leiomyomatosis peritonei.
AB  - We describe a 41-year-old woman with disseminated leiomyomatosis peritonei who
      underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy.
      Images obtained from laparoscopy and histopathology are presented.

PMID- 16275252
TI  - Births using sperm retrieved via immediate microdissection of a solitary testis
      with cancer.
AB  - OBJECTIVE: To determine the feasibility of achieving births using sperm retrieved
      from a solitary testis with cancer. DESIGN: Prospective clinical study of
      azoospermic men with testis cancer in a solitary testis. SETTING: Infertility
      patients in an academic environment. PATIENT(S): Azoospermic men with previous
      history of orchiectomy and testis cancer in a remaining solitary testis.
      INTERVENTION(S): Viable sperm were retrieved by immediate microdissection of
      paratumor testicular tissue from orchiectomy specimen. MAIN OUTCOME MEASURE(S):
      Live births were achieved using sperm from immediate microdissection of
      orchiectomy specimen with testis cancer. CONCLUSION(S): Azoospermic men with
      cancer in a solitary testis have potential for fertility.

PMID- 16275253
TI  - Four pregnancies in nonmosaic Klinefelter's syndrome using cryopreserved-thawed
      testicular spermatozoa.
AB  - OBJECTIVE: To investigate feasibility of using cryopreserved-thawed testicular
      spermatozoa from patients with nonmosaic Klinefelter's syndrome for
      intracytoplasmic sperm injection (ICSI). DESIGN: Case report. SETTING: University
      based hospital and IVF clinic. PATIENT(S): Six patients with nonmosaic
      Klinefelter's syndrome who underwent testicular sperm extraction for ICSI.
      INTERVENTION(S): Microdissection testicular sperm extraction (TESE) and ICSI.
      MAIN OUTCOME MEASURE(S): We compared results of ICSI using cryopreserved
      testicular spermatozoa with those previously reported in Klinefelter's syndrome
      and those in nonobstructive azoospermia patients using cryopreserved testicular
      spermatozoa at our institution with respect to embryo cleavage rate, implantation
      rate, and pregnancy outcome. RESULT(S): Four of six patient couples with
      successful microdissection TESE achieved pregnancy using cryopreserved-thawed
      testicular spermatozoa. One pregnancy resulted in early-pregnancy abortion, two
      in delivery of healthy singleton girls, and one delivery of a healthy singleton
      boy. CONCLUSION(S): Cryopreserved-thawed testicular spermatozoa can be used
      successfully for ICSI in patients with nonmosaic Klinefelter's syndrome.

PMID- 16275254
TI  - A woman with spontaneous premature ovarian failure gives birth to a child with
      fragile X syndrome.
AB  - OBJECTIVE: To inform clinicians about a reproductive risk associated with
      spontaneous premature ovarian failure and the fragile X mental retardation 1 gene
      (FMR1). DESIGN: Case report. SETTING: National Institutes of Health Clinical
      Center. PATIENT(S): A 35-year-old woman with confirmed spontaneous premature
      ovarian failure. INTERVENTION(S): FMR1 genetic testing. MAIN OUTCOME MEASURE(S):
      Number of CGG trinucleotide repeats in the 5' untranslated region of FMR1.
      RESULT(S): Despite having ovarian failure the woman subsequently conceived and
      delivered a son with fragile X syndrome (>200 CGG repeats). She was then found to
      carry an FMR1 premutation (85 CGG repeats). CONCLUSION(S): This is a real-life
      manifestation of a theoretical risk; a woman conceived subsequent to the
      diagnosis of spontaneous premature ovarian failure and has a child who manifests
      mental retardation due to fragile X syndrome. Women with spontaneous premature
      ovarian failure are at increased risk of having an FMR1 premutation and should be
      informed of the availability of fragile X testing. Should an FMR1 premutation be
      uncovered, this will allow patients to make informed reproductive decisions and
      help clinicians to properly diagnose family members who may have menstrual
      irregularity, developmental delay, or neurologic symptoms.

PMID- 16275255
TI  - Sciatic endometriosis diagnosed by computerized tomography-guided biopsy and CD10
      immunohistochemical staining.
AB  - OBJECTIVE: To report a case of sciatic endometriosis diagnosed by computerized
      tomography (CT)-guided biopsy in combination with CD10 immunohistochemical
      staining. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 33
      year-old Japanese woman complaining of right-sided sciatica. INTERVENTION(S):
      Transgluteal computerized tomography (CT)-guided needle biopsy of a mass in the
      course of the right sciatic nerve was conducted for a histologic diagnosis. MAIN
      OUTCOME MEASURE(S): Histologic study with hematoxylin and eosin staining and CD10
      immunohistochemical staining was performed. RESULT(S): Computerized tomography
      guided biopsy was performed without any complication. CD10 staining distinguished
      endometrial stromal cells. CONCLUSION(S): Computerized tomography-guided biopsy
      followed by CD10 immunohistochemical staining is a minimally invasive procedure
      for accurate diagnosis of sciatic endometriosis.

PMID- 16275256
TI  - Ovarian cortical transplantation may be an alternative to hormone therapy in
      patients with early climacterium.
AB  - OBJECTIVE: To discuss the 18-month follow-up results of fresh ovarian cortical
      tissue transplant. DESIGN: Case study. SETTING: Academic medical center.
      PATIENT(S): A 46-year-old patient who was operated on for uterine fibroids, and
      who then received an ovarian tissue transplant in July 2003. INTERVENTION(S):
      Serum hormone levels were measured at 3-month intervals. MAIN OUTCOME MEASURE(S):
      Follicular development evident by ultrasound examination; serum hormone levels
      (FSH, LH, E2). RESULT(S): Preoperative and 3rd-, 6th-, 9th-, 12th-, 15th-, and
      18th-month hormone levels were, respectively, as follows: FSH: 9.06, 79.5, 13.7,
      16.66, 51.91, 44.37, and 24.17 mIU/mL; LH: 5.91, 33.92, 8.78, 21.83, 38.31,
      40.85, and 22.4 mIU/mL; E2: 166, 46, 48, 117, 31, 14.4, and 137.7 pg/mL.
      Folliculogenesis was confirmed by ultrasonography at the 6th, 9th, and 18th
      months during the follow-up period. CONCLUSION(S): Fresh ovarian
      autotransplantation may be a logical alternative for hormonal support for a
      specific patient group.

PMID- 16275257
TI  - Ultrasound-guided miduterine cavity embryo transfer is associated with a
      decreased incidence of retained embryos in the transfer catheter.
AB  - After initiating a policy of ultrasound-guided miduterine cavity embryo transfer
      (ET) on August 1, 2001, the incidence of retained embryos in the transfer
      catheter declined significantly from 4.2% (46 of 1,101 ETs) during the time
      interval January 1, 2000 to July 31, 2001, to 0.7% (6 of 908 ETs) during the time
      interval August 1, 2001 to December 31, 2002. Blood on the transfer catheter (38%
      vs. 19%) occurred with significantly greater frequency at ET in which embryos
      were retained; ETs of > or =4 embryos were more likely to be associated with
      retained embryos than ETs of <4 embryos (3.7% vs. 2.2%), and both the clinical
      pregnancy rate (PR) and implantation rate (IR) were lower when embryo retention
      occurred at ET than they were when embryos were not retained (25% vs. 34%
      clinical PR; 12% vs. 19% IR).

PMID- 16275258
TI  - Assessment of wishes regarding disposition of oocytes and embryo management among
      ovum donors in an anonymous egg donation program.
AB  - Revealing possible clinical scenarios to potential anonymous donors for their
      donated oocytes appears to uncover ambivalence in the majority of prospective
      candidates about their donation and unwillingness in some to proceed. Full
      disclosure to a prospective donor candidate of the program's policies for
      directives of donated oocytes and embryo management emphasizes the importance of
      the informed consent process and how it may affect the decision to donate.

PMID- 16275259
TI  - Comparative genomic hybridization of ectopic pregnancies that fail methotrexate
      therapy.
AB  - Ectopic pregnancies that fail methotrexate therapy are predominantly euploid by
      comparative genomic hybridization (CGH). This feasibility study also confirms
      that formalin-fixed paraffin-embedded gestational tissue can successfully undergo
      CGH.

PMID- 16275260
TI  - The M235T polymorphism of the angiotensinogen gene in women with polycystic ovary
      syndrome.
AB  - To explore the relationship between variation in AGT M235T gene and the
      development of the polycystic ovary syndrome (PCOS) and its sequelae, in the
      present study we evaluated AGT polymorphism M235T in women with PCOS and in a
      control group. Moreover, to detect any relationship between AGT M235T variation
      and intermediate and quantitative traits relevant to the pathogenesis of
      cardiovascular disease and PCOS, we looked for genotype-dependent differences
      within the subjects with PCOS.

PMID- 16275261
TI  - Copy number of DAZ genes in infertile men.
AB  - The aim of the study was to define the relevance of deletions and duplications
      within the DAZ gene cluster to male factor infertility in a population of 90
      infertile men and a control of 50 fertile men using real-time polymerase chain
      reaction (PCR). We conclude that partial deletions of the DAZ genes are
      associated with oligozoospermia but not with azoospermia; however, an increased
      number of DAZ genes does not seem to be a statistically significant risk factor
      for spermatogenic failure.

PMID- 16275262
TI  - Effect of cetrorelix acetate on apoptosis and apoptosis regulatory factors in
      cultured uterine leiomyoma cells.
AB  - This report suggests the possibility that a gonadotropin-releasing hormone (GnRH)
      antagonist initiates apoptosis not only by causing a sex hormone deficit by
      inhibiting GnRH secretion in the pituitary gland, but also by acting directly on
      leiomyoma cells promoting apoptosis.

PMID- 16275263
TI  - Serum luteinizing hormone in patients undergoing ovarian stimulation with
      gonadotropin-releasing hormone antagonists and recombinant follicle-stimulating
      hormone and its relationship with cycle outcome.
AB  - The serum LH was determined on days 3, 6, and 8 of stimulation and on the day of
      hCG in 110 normogonadotropic patients undergoing controlled ovarian
      hyperstimulation (COH) for IVF induced with GnRH antagonists and recombinant FSH,
      creating three groups of patients according to Tukey's hinges (percentiles 25 and
      75) for each determination. No differences were observed between the number of
      oocytes recovered or the fertilization, implantation, and pregnancy rates (PR) of
      the groups, although patients with high serum LH levels during stimulation showed
      significantly higher serum E2 levels on the day of hCG.

PMID- 16275264
TI  - Circulating antibodies to human spermatozoa in patients with ulcerative colitis.
AB  - The existence of enhanced humoral immunity against sperm antigens in patients
      with ulcerative colitis might be a result of the increased intestinal
      permeability, and may be associated with immunization against antigens of the
      common intestinal flora possessing common antigenicity with spermatozoa. The
      result of these two processes is statistically significant increased antisperm
      antibody (ASA) incidence in patients with ulcerative colitis compared to the
      healthy blood donors of proven fertility without clinical symptoms of
      inflammatory bowel diseases at the same age.

PMID- 16275265
TI  - Transvaginal ultrasound and operative hysteroscopy in women undergoing medical
      termination of pregnancy as a part of routine follow-up.
AB  - Follow-up of the first cohort of 191 patients who underwent medical abortion in a
      tertiary medical center included postmenstruation transvaginal sonography (TVS),
      even in asymptomatic patients. Suspected products of gestation by TVS were found
      in 3.7% of the asymptomatic women, and residual products of gestation were
      diagnosed by hysteroscopy in 85.7% of such cases.

PMID- 16275266
TI  - Isolation of a sperm-agglutinating factor from Staphylococcus aureus isolated
      from a woman with unexplained infertility.
AB  - Spermatozoal agglutinating factor (SAF) that agglutinates human spermatozoa has
      been isolated from Staphylococcus aureus. By scanning electron microscopy,
      Staphylococcus aureus adherence was observed on sperm tails.

PMID- 16275267
TI  - Somatic mutational analysis of DAX1 in testes from men with idiopathic
      azoospermia.
AB  - Mutations in the orphan nuclear receptor DAX1 (NR0B1) cause X-linked adrenal
      hypoplasia congenital (AHC), a disorder characterized by primary adrenal failure,
      hypogonadotropic hypogonadism. and azoospermia. We tested the hypothesis that
      DAX1 somatic mutations in human testis may cause azoospermia. DAX1 sequencing
      analysis in 15 testicular biopsy samples from men with idiopathic nonobstructive
      azoospermia did not reveal mutations in the coding region of the gene. We
      conclude that somatic abnormalities in DAX1 are absent or uncommon in these
      patients.

PMID- 16275268
TI  - Mifepristone may inhibit the midcycle gonadotropin surge at both ovarian and
      pituitary sites of action.
AB  - The ability of mifepristone to delay ovulation is thought to be based on the
      antigonadotropic effects of the drug. In the current work, late-follicular phase
      administration of mifepristone resulted in decrease in both circulating FSH and
      inhibin B, suggesting both central and ovarian sites of action.

PMID- 16275269
TI  - Laser zona drilling does not induce hsp70i transcription in blastomeres of eight
      cell mouse embryos.
AB  - To assess whether zona drilling with a 1,480-nm laser induces heat shock in eight
      cell embryos, we measured hsp70i RNA levels in sets of single blastomeres
      isolated after laser treatment of mouse embryos that had or had not been heated
      at 43 degrees C. Unlike heating, laser zona drilling did not stimulate hsp70i
      expression, even in the blastomeres closest to the laser beam, corroborating the
      safety of this procedure for assisted reproduction.

PMID- 16275270
TI  - Do variations in assisted reproductive technology programs' screening practices
      indicate a need for national guidelines? Another perspective.
AB  - Some see an "alarming inconsistency" in candidate-screening practices of assisted
      reproductive technology (ART) programs and call for common guidelines. However,
      reasonable people can disagree about who should be prevented from having children
      and why.

PMID- 16275271
TI  - Source of the extra pronucleus after intracytoplasmic sperm injection?

PMID- 16275273
TI  - Laparoscopic vasovasostomy.

PMID- 16275274
TI  - Evidence-based medicine is gaining momentum.

PMID- 16275277
TI  - Determination of organophosphorus pesticides in cucumber and potato by stir bar
      sorptive extraction.
AB  - Organophosphorus pesticides (OPPs) in vegetables were determined by stir bar
      sorptive extraction (SBSE) and capillary gas chromatography with thermionic
      specific detection (TSD). Hydroxy-terminated polydimethylsioxane (PDMS) prepared
      by sol-gel method was used as extraction phase. The effects of extraction
      temperature, salting out, extraction time on extraction efficiency were studied.
      The detection limits of OPPs in water were < or = 1.2 ng/l. This method was also
      applied to the analysis of OPPs in vegetable samples and matrix effect was
      studied. Linear ranges of OPPs in vegetable samples were 0.05-50 ng/g with
      detection limits < or =0.15 ng/g and the repeatability of the method was less
      than 20% relative standard deviation.

PMID- 16275278
TI  - Development of a solid-phase microextraction method for direct determination of
      pentachlorophenol in paper and board samples: Comparison with conventional
      extraction method.
AB  - A solid-phase microextraction (SPME) method has been developed for the
      determination of pentachlorophenol (PCP) in paper and board samples. The
      analytical procedure involves direct extraction of PCP from paper and board
      samples and determination by gas chromatography with electron capture detection
      (GC-ECD). Two kinds of commercially available fibres; 100 microm
      polydimethylsiloxane (PDMS), apolar, and 85 microm polyacrylate (PA), quite
      polar, were evaluated to determine the extraction efficiency of
      pentachlorophenol. Parameters affecting the extraction process, such as
      temperature and time, were studied. Moreover, time of desorption and the effect
      of addition of salt were also investigated. The optimized procedure was applied
      to the analysis of pentachlorophenol (PCP) in five samples of virgin and recycled
      paper and board. The PCP content was determined by GC-ECD. To evaluate the
      effectiveness of the proposed method, it was compared with conventional
      extraction method with liquid-liquid extraction and derivatization. Detection
      limit of 0.015 microg/g for PCP in paper was achieved with a RSD of 14%.

PMID- 16275279
TI  - Predictive modeling of protein adsorption along the bed height by taking into
      account the axial nonuniform liquid dispersion and particle classification in
      expanded beds.
AB  - Expanded bed adsorption (EBA) is a special chromatography technique with perfect
      classification of adsorbent particles in the column, thus the performance of
      protein adsorption in expanded beds is particular, obviously nonuniform and
      complex along the column. Detailed description of the complex adsorption kinetics
      of proteins in expanded bed is essential for better analyzing of adsorptive
      mechanisms, the design of chromatographic processes and the optimization of
      operation parameters of EBA processes. In this work, a theoretical model for the
      prediction of protein adsorption kinetics in expanded beds was developed by
      taking into account the classified distribution of adsorbent particles along the
      bed height, the nonuniform behaviors of axial liquid dispersion, the axial
      variation of local bed voidage as well as the axial changes of target component
      mass transfer. The model was solved using the implicit finite difference scheme
      combining with the orthogonal collocation method, and then applied to predict the
      breakthrough behaviors of bovine serum albumin (BSA) on Streamline DEAE and
      lysozyme on Streamline SP along the bed height in expanded beds under various
      conditions. In addition, the experiments of front adsorption of BSA on Streamline
      DEAE at different axial column positions were carried out to reveal the
      adsorption kinetics of BSA along the bed height in a 20 mm I.D. expanded bed, and
      the influences of liquid velocity and feed concentration on the breakthrough
      behaviors were also analyzed. The breakthrough behaviors predicted by the present
      model were compared with the experimental data obtained in this work and in the
      literature published. The agreement between the prediction and the experimental
      breakthrough curves is satisfied.

PMID- 16275280
TI  - The adsorption mechanism of nortryptiline on C18-bonded Discovery.
AB  - The adsorption isotherms of an ionizable compound, nortriptyline, were accurately
      measured by frontal analysis (FA) on a C(18)-Discovery column, first without
      buffer (in an aqueous solution of acetonitrile at 15%, v/v of ACN), then with a
      buffer (in 28%, v/v ACN solution). The buffers were aqueous solutions containing
      20 mM of formic acid or a phosphate buffer at pH 2.70. The linear range of the
      isotherm could not be reached with the non-buffered mobile phase using a dynamic
      range larger than 40,000 (from 1.2 x 10(-3) g/L to 50 g/L). With a 20 mM buffer
      in the liquid phase, the isotherm is linear for concentrations of nortriptyline
      inferior to 10(-3) g/L (or 3 micromol/L). The adsorption energy distribution
      (AED) was calculated to determine the heterogeneity of the adsorption process.
      AED and FA were consistent and lead to a trimodal distribution. A tri-Moreau and
      a tri-Langmuir isotherm models accounted the best for the adsorption of
      nortriptyline without and with buffer, respectively. The nature of the buffer
      affects significantly the middle-energy sites while the properties of the lowest
      and highest of the three types of energy sites are almost unchanged. The
      desorption profiles of nortriptyline show some anomalies in relation with the
      formation of a complex multilayer adsorbed phase of acetonitrile whose excess
      isotherm was measured by the minor disturbance method. The C(18)-Discovery column
      has about the same total saturation capacity, around 200 g of nortriptyline per
      liter of adsorbent (or 116 mg/g), with or without buffer. About 98-99% of the
      available surface consists in low energy sites. The coexistence of these
      different types of sites on the surface solves the McCalley's enigma, that the
      column efficiency begins to drop rapidly when the analyte concentration reaches
      values that are almost one hundred times lower than those that could be predicted
      from the isotherm data acquired under the same experimental conditions. Due to
      the presence of some relatively rare high energy sites, the largest part of the
      saturation capacity is not practically useful.

PMID- 16275281
TI  - Synthesis and characterization of a novel resorcinarene-based stationary phase
      bearing polar headgroups for use in reversed-phase high-performance liquid
      chromatography.
AB  - A novel silica-bonded stationary phase containing a functionalized resorcinarene
      selector was prepared by a straightforward synthesis. The complete modification
      of all resorcinic hydroxyl groups was achieved by reaction with isopropyl
      isocyanate. The derivatized resorcinarene selector was subsequently immobilized
      via the four alkenyl chains containing a terminal double bond by a free radical
      induced reaction on mercaptopropyl-functionalized silica. A comprehensive
      characterization of the resulting bonded stationary phase was carried out by
      solid state NMR, IR and elemental analysis. The resulting selector is defined as
      a "polar headed" reversed phase since the highly ordered polar carbamate groups
      of the new stationary phase are located, compared to conventional polar embedded
      stationary phases, at a greater distance from the silica surface. Thus a new
      concept is introduced in the field of polar modified reversed-phase HPLC. The
      properties of the novel stationary phase are demonstrated by comparison with
      commercially available reversed phases.

PMID- 16275282
TI  - Investigation of the adsorption behaviour of a chiral model compound on a
      tartardiamide-based network-polymeric chiral stationary phase.
AB  - The adsorption behaviour of the enantiomers of 2-phenylbutyric acid on the chiral
      stationary phase (CSP) Kromasil CHI-TBB was studied using hexane/MTBE (90/10) as
      eluent. Adsorption isotherms were acquired at 40 different enantiomer
      concentrations in the interval between 7.6 microM and 305 mM, an approximately
      40,000-fold dynamic range. The adsorption data fitted well to the bi-Langmuir
      model, indicating a heterogeneous surface with two different types of adsorption
      sites having different equilibrium constants and capacities; namely one chiral
      site and one non-chiral site. A comparison with earlier adsorption studies on
      modern CSPs revealed that the capacity value of the "true" chiral site of
      Kromasil CHI-TBB is the largest reported so far. The elution profiles simulated
      with these parameters show excellent agreement with the corresponding
      experimental profiles. Guidelines for comparisons of loading capacities of CSPs
      are presented.

PMID- 16275283
TI  - High performance liquid chromatography post-column chemiluminescence
      determination of sulfonamide residues in milk at low concentration levels using
      bis[4-nitro-2-(3,6,9-trioxadecyloxycarbonyl)phenyl] oxalate as chemiluminescent
      reagent.
AB  - The determination of seven sulfonamides by means of HPLC with chemiluminescence
      detection is proposed for the first time. The analytes are derivatized with
      fluorescamine, separated and subsequently they participate in the post-column
      chemiluminescence (CL) peroxyoxalate system using imidazole as a catalyst. Among
      the different peroxyoxalates tested, bis[4-nitro-2-(3,6,9
      trioxadecyloxycarbonyl)phenyl] oxalate provides higher sensitivities and
      stabilities, avoiding precipitation problems. A rigorous optimization of the
      significant variables by means of experimental designs has been developed in
      order to reconcile the chromatographic conditions with the CL reaction. The
      method provides detection limits in the low microgl(-1) range and has been
      satisfactorily applied to the analysis of spiked raw milk samples.

PMID- 16275284
TI  - Simulating phenol high-performance liquid chromatography retention times as the
      pH changes. Mobile phase pH versus buffer pH.
AB  - The HPLC retention times of several substituted phenols have been measured and
      simulated using Advanced Chemistry Development's LC simulator, using 50%
      acetonitrile (ACN) as the mobile phase. For alkyl- and nitro-substituted phenols,
      the quality of the simulation improves when pH of the mobile phase is estimated
      and used in the simulation. Simply using the pH of the buffer gives simulation
      results that are not as close to the actual retention times. However, the
      opposite is the case for halogenated phenols. The pK(a) values in 50% ACN for
      some of these phenols have also been determined, which tend to be one unit higher
      than the aqueous pK(a) values reported in the literature.

PMID- 16275285
TI  - Quantitative determination of benzalkonium chloride in treated wood by solid
      phase extraction followed by liquid chromatography with ultraviolet detection.
AB  - Ammoniacal copper quat (ACQ) compound wood preservative is comprised of copper
      and quaternary ammonium compounds with benzalkonium chloride (BAC) as the active
      ingredient. Solid-phase extraction (SPE) followed by liquid chromatography with
      ultraviolet detection (LC-UV) was developed for quantitative determination of BAC
      in treated wood. Five species of wood were used, Japanese cedar (Cryptomeria
      japonica), Japanese larch (Larix leptolepis), Yezo spruce (Picea jezoensis),
      Sakhalin fir (Abies sachalinensis), and western hemlock (Tsuga heterophylla). BAC
      used in the present study was composed of 66% C12, 33% C14 and less than 1% C16.
      BAC was added to each wood species (500 mg) then extracted with HCl-ethanol (20
      ml) and quantitatively determined with LC-UV (262 nm). Wood extractives from the
      heartwood of each species, except western hemlock, interfered with quantitative
      determination of BAC, but SPE with an Oasis MCX cartridge was effective in
      preventing this. Using the present methods, BAC homologue peaks were clearly
      confirmed without interference. Recoveries from wood ranged from 92 to 101% and
      the limit of quantitation was approximately 240 microg/g wood for the C12 and C14
      homologues.

PMID- 16275286
TI  - Examination of soil contaminated by coal-liquids by size exclusion chromatography
      in 1-methyl-2-pyrrolidinone solution to evaluate interference from humic and
      fulvic acids and extracts from peat.
AB  - Soil from a redundant coke oven site has been examined by extraction of soluble
      materials using 1-methyl-2-pyrrolidinone (NMP) followed by size exclusion
      chromatography (SEC) of the extracted material. The extracted material was found
      to closely resemble a high temperature coal tar pitch. Standard humic and fulvic
      acids were also examined since these materials are very soluble in NMP and would
      be extracted with pitch if present in the soil. Humic substances derived from
      peat samples and NMP-extracts of peats were also examined. The results show that
      the humic and fulvic substances were not extracted directly by NMP from peats.
      They were extracted using caustic soda solution and were different from the peat
      extracts in NMP. These results indicate that humic and fulvic acids were soluble
      in NMP in the protonated polyelectrolyte form but not in the original native
      polyelectrolyte form. The extraction of soil using NMP followed by SEC appears to
      be a promising method for identifying contamination by coal-based industries.

PMID- 16275287
TI  - Efficient enantiomeric analysis of primary amines and amino alcohols by high
      performance liquid chromatography with precolumn derivatization using novel
      chiral SH-reagent N-(R)-mandelyl-(S)-cysteine.
AB  - Novel N-acylated-(S)-cysteine derivative-N-(R)-mandelyl-(S)-cysteine (R-NMC),
      containing additional chiral center, aromatic and polar alpha-substituents in
      contrast to the traditionally used enantiomerically pure thiols, has been
      demonstrated to be an efficient SH-reagent for enantiomeric HPLC analysis of
      primary nonfunctionalized amines and amino alcohols after precolumn
      derivatization with o-phthalaldehyde. The R-NMC-derived isoindoles as well as
      adducts formed using traditional SH-reagents had a characteristic absorption
      maximum at 340 nm with a molar absorbance 6000 M(-1) cm(-1), were stable during
      the HPLC-analysis and highly fluorescent allowing to detect 1 fmol of amino
      compound. Using diastereomeric R-NMC all tested amino alcohols were resolved
      effectively as well as nonfunctionalized amines, some of which were not resolved
      by a direct method on a chiral phase. Applying traditional enantiomeric N-acetyl
      (S)-cysteine (NAC) only some isoindoles formed by aliphatic amino alcohols have
      been separated satisfactorily. The enhanced selectivity for R-NMC-derived isomers
      has been achieved, obviously, due to the involvement of the substituents at an
      extra chiral center into additional intramolecular interactions.

PMID- 16275288
TI  - Sensitive determination of phenolic compounds using high-performance liquid
      chromatography with cerium(IV)-rhodamine 6G-phenolic compound chemiluminescence
      detection.
AB  - A simple, selective and sensitive determination method of 20 phenolic compounds
      has been developed using high-performance liquid chromatography (HPLC) with
      chemiluminescence detection. The method is based on the chemiluminescent
      enhancement by phenolic compound of the cerium(IV)-rhodamine 6G system in
      sulfuric acid medium. Twenty phenolic compounds were separated on a XDB-C(8)
      column with a gradient elution using a mixture of methanol and 1.0% acetic acid
      as a mobile phase. Under the optimized conditions, a linear working range extends
      2 orders of magnitude with the relative standard deviations of intra- and inter
      day precision below 4.0%, and the detection limits (S/N = 3) were in the range of
      1.5-82.1 ng/ml. The chemiluminescence reaction was compatible with the mobile
      phase of high-performance liquid chromatography. The proposed method has been
      successfully applied to the assay of phenolic compounds in red wine without any
      pretreatment.

PMID- 16275289
TI  - Alternative approaches for the estimation of the band broadening parameters in
      single-detection size exclusion chromatography.
AB  - New approaches for the determination of the extent of symmetric and asymmetric
      band broadening (BB) in size exclusion chromatography (SEC) are presented. For
      this purpose raw data was simulated by starting with either a theoretical Poisson
      number chain length distribution (NCLD), or a log-normal weight chain length
      distribution (WCLD). Each distribution was first converted to a BB-free mass
      chromatogram, as typically obtained from a standard differential refractive index
      detector. Then, the broadened (or "measured") chromatograms were simulated by
      convoluting the BB-free chromatograms with a BB function, which was assumed to
      follow symmetrical (Gauss) as well as unsymmetrical (exponentially modified
      Gauss) function. A broad range of BB parameters (standard deviation, sigma(BB),
      and exponential decay, tau(BB)) was used for the simulations. The approaches are
      based on the determination of the points of inflection belonging to the peak of
      the broadened chromatogram, and closed as well as empirically derived equations
      connecting the peak width, its variance, and the parameters sigma(BB) and
      tau(BB). The developed methods are applicable for Poisson distributions well
      above a peak chain length of 100.

PMID- 16275290
TI  - Rational method development strategies on a fluorinated liquid chromatography
      stationary phase: mobile phase ion concentration and temperature effects on the
      separation of ephedrine alkaloids.
AB  - Fluorinated, silica-based stationary phases are becoming increasingly popular
      alternatives to traditional alkyl phases owing to their differential selectivity
      and retention for a variety of analyte classes. In this report, the ion-exchange
      mechanisms characteristic of a fluorinated phase are exploited to rapidly develop
      separation conditions for ephedrine alkaloids and synephrine using a mobile phase
      compatible with mass spectrometry. A linear relationship of basic analyte
      retention with the reciprocal of ammonium acetate concentration is first
      established. This linear relationship can then be used to optimize retention and
      selectivity in just two experiments. The relationship of retention with
      temperature is also explored. Greater retention with increasing temperature is
      demonstrated on the fluorinated phase at high percentages of organic modifier,
      which is in contrast to behavior observed in typical reversed-phase separations.
      The unexpected observation is explicated based on the reduction in solvent
      solvating power with increasing temperature. As solvation power of the mobile
      phase decreases, decreased solvation of both mobile phase and ionized surface
      groups of the stationary phase leads to stronger interactions between analyte and
      stationary phase. Both mobile phase ion concentration and temperature are shown
      to be powerful tools for the manipulation of analyte retention and selectivity.

PMID- 16275291
TI  - Ion-exchange chromatography of hepatitis B virus surface antigen from a
      recombinant Chinese hamster ovary cell line.
AB  - About 10% of the Chinese population are chronic carriers of hepatitis B virus
      (HBV). Thus, the development of a highly efficient process for the preparation of
      a vaccine based on a recombinant hepatitis B surface antigen (HBsAg) is very
      important to the Chinese national immunization program. To this end, the ion
      exchange chromatography recovery of CHO-HBsAg from a recombinant Chinese hamster
      ovary cell line was shown to increase from about 55 to 80% by the addition of 1%
      poly(ethylene glycol) (PEG 10,000) to the mobile phase. Furthermore, based on
      analysis by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS
      PAGE), the intact glycoprotein form of CHO-HBsAg was completely preserved by the
      addition of PEG. In the absence of PEG the glycoprotein form of CHO-HBsAg was
      also spread out into the high salt elution fraction. High-performance size
      exclusion chromatography with on-line multiangle-laser-light scattering (HPSEC
      MALLS) analysis was performed to monitor the status of the CHO-HBsAg aggregate
      structure assembly, particle size and molecular weight distribution after each
      purification step, and the results showed further that the presence of PEG
      facilitated the separation and recovery of intact glycoprotein form of CHO-HBsAg
      and promoted their assembly to proper virus-like particles, which are both
      important features and prerequisites of their immunogenicity.

PMID- 16275292
TI  - Quantification of long chain polyunsaturated fatty acids by gas chromatography.
      Evaluation of factors affecting accuracy.
AB  - The accurate and reproducible analysis of long-chain polyunsaturated fatty acids
      (PUFA) is of growing importance. Especially for labeling purposes, clear
      guidelines are needed in order to achieve optimum accuracy. Since calibration
      standards cannot be used for method validation due to the instability of PUFAs,
      there is no direct way to check for the absence of systematic errors. In this
      study the sources of error that weaken the accuracy were evaluated using
      theoretical considerations and calibration standards with corrected composition.
      It was demonstrated that the key role for optimum accuracy lies in the
      optimization of the split injection system. Even when following the instructions
      outlined in the official methods of the American Oil Chemist's Society (AOCS),
      systematic errors of more than 7% can arise. Clear guidelines regarding system
      calibration and selection of appropriate internal standards (IS) can improve
      precision and accuracy significantly.

PMID- 16275293
TI  - Comparative study on the gas-phase adsorption of hexane over zeolites by
      calorimetry and inverse gas chromatography.
AB  - The scope of this work is to carry out a systematic comparison of inverse gas
      chromatography (IGC) and microcalorimetry as tools for the study of the gas-phase
      adsorption of organic vapours (using hexane as model compound) on zeolitic
      materials (using different Mn, Co and Fe-exchanged NaX and CaA zeolites).
      Adsorption isotherms were recorded using both techniques in the temperature range
      of 150-250 degrees C, being observed that the shape of the isotherms obtained
      with the dynamic (IGC) and static (microcalorimetry) techniques was surprisingly
      similar in the pressure range at which both techniques are applicable (low
      surface coverages). Concerning to the measurement of the strength of the
      adsorption, calorimetric data provide two parameters related to the adsorption
      enthalpy: the initial differential heat and the isosteric adsorption enthalpy. A
      great coincidence was found between the last one and the adsorption enthalpy
      determined by IGC (4-20% of difference, depending on the studied material). The
      behaviour of the initial differential heat depends strongly on the studied
      material, being in some cases closely related to the other two parameters and
      temperature-independent (in the case on Mn-exchanged zeolites), whereas for the
      Co-CaA and Fe-CaA zeolites, it is temperature-dependent, being not correlated
      with the other parameters in this case. The main conclusion of this work is that
      IGC is an attractive alternative to the static microcalorimetric data for
      obtaining information on the adsorption of organic compounds on microporous
      materials.

PMID- 16275294
TI  - Gas chromatography with atomic emission detection for dimethylselenide and
      dimethyldiselenide determination in waters and plant materials using a purge-and
      trap preconcentration system.
AB  - Dimethylselenide (DMSe) and dimethyldiselenide (DMDSe) were determined in plant
      and water samples by capillary gas chromatography using microwave induced-plasma
      atomic emission spectrometry for detection. The analytes were leached from the
      solid samples into methanol by using an ultrasonic probe, and a portion of the
      extract was preconcentrated by means of a purge-and-trap system before being
      chromatographed. The analytes were directly purged from the water samples in the
      presence of 6% (v/v) methanol. Element-specific detection and quantification was
      carried out by monitoring the selenium (196 nm) emission line. Calibration curves
      were obtained by plotting peak area versus concentration and the correlation
      coefficients for linear calibration were 0.9999 for both analytes. Detection
      limits of 0.8 and 1.1 ng l(-1) were obtained for DMSe and DMDSe, respectively,
      for water samples. For plant materials, the detection limits calculated for 0.5 g
      samples were 0.3 and 0.4 ng g(-1) for DMSe and DMDSe, respectively. Concentration
      levels of DMSe ranging from 1.2 to 4.2 ng g(-1) were found in some of the plant
      materials analyzed. No DMDSe was found in any of the samples. The accuracy of the
      method was checked by analyzing different spiked water and plant samples.

PMID- 16275295
TI  - Preferential interactions in pigmented, polymer blends - C.I. Pigment Blue 15:4
      and C.I. Pigment Red 122 - as used in a poly(carbonate)-poly(butylene
      terephthalate) polymer blend.
AB  - Some important characteristics of selected pigments have been evaluated, using
      the inverse gas chromatography (IGC) technique, that indicate the occurrence of
      preferential interactions in pigmented polymer blends. Attention has been given
      to copper phthalocyanine pigments and to quinacridone pigments incorporated in
      polycarbonate-poly(butylene terephthalate) blends. Selected supporting techniques
      were used to provide supplementary information concerning the pigments of
      interest, C.I. Pigment Blue 15:4 and C.I. Pigment Red 122. For C.I. Pigment Red
      122 and for C.I. Pigment Blue, the dispersive component of the surface free
      energy decreases as the temperature increases, indicating the relative ease with
      which the molecules can be removed from the surface.

PMID- 16275296
TI  - Comparison of titania, zirconia, and silica stationary phases for separating
      diesel fuels according to hydrocarbon group-type by supercritical fluid
      chromatography.
AB  - Silica, zirconia, and titania columns were compared for their ability to separate
      diesel samples into saturates, mono-, di-, tri-, and polyaromatics by
      supercritical fluid chromatography (SFC) using pure CO(2) according to ASTM
      method D 5186-03. A titania column coupled in series to a silica column was found
      to provide the highest overall group-type resolutions based on 20 model
      compounds, with resolutions as high as 14.7 for saturates versus monoaromatics
      and 11.9 for monoaromatics versus diaromatics. An oilsands-derived Synfuel light
      diesel, a commercial Ontario diesel, and a heavy Shell Canada Ltd. diesel
      blending feedstock were studied on a titania-silica coupled column as well as on
      a conventional silica column. The Synfuel results were similar (within 0.5 mass%)
      on both the conventional bare silica column and the titania-silica coupled
      column. The heavier commercial diesel and diesel blending feedstock samples
      yielded different results on the titania-silica coupled column compared to the
      silica column alone, demonstrating the importance of achieving the highest
      possible resolutions when baseline separation of group-types is not obtained.

PMID- 16275297
TI  - A new ionic liquid dimethyldinonylammonium bromide as a flow modifier for the
      simultaneous determination of eight carboxylates by capillary electrophoresis.
AB  - Two new methods of capillary zone electrophoresis based on aqueous phosphate
      running buffers with UV spectrophotometric detection were developed and optimized
      for the determination of eight carboxylates as copper complexes. Metalcomplexes
      are negatively charged, so measurements were made as anion analyses with flow
      reversal in the capillary. Two flow modifiers were used: a common
      tetradecyltrimethylammonium bromide (TTAB) and a new ionic liquid
      dimethyldinonylammonium bromide (DMDNAB). The methods were compared to each
      other. Better separation was achieved with DMDNAB as the flow modifier. Method
      development was done using a fused silica capillary (61 cm x 50 microm i.d.).
      Optimization was done using 95 mmol L(-1) phosphate buffer with TTAB or DMDNAB in
      the concentration 0.5 mmol L(-1) at pH 7.1. A -20 kV voltage and direct UV
      detection at 254 nm was used in measurements. In both CE methods all the peaks in
      the electropherograms were properly separated, the calibration plots gave good
      correlation coefficients and all eight carboxylates were detected in less than
      7.5 min. The two methods were tested with natural water samples and a paper mill
      sample, and proved to be feasible.

PMID- 16275298
TI  - Migration behavior of weakly retained, charged analytes in voltage-assisted micro
      high performance liquid chromatography.
AB  - The application of voltage in micro-high performance liquid chromatography (micro
      HPLC) creates a system where separation is governed by a hybrid differential
      migration process, which entails the features of both HPLC and capillary zone
      electrophoresis (CZE), i.e., chromatographic retention and electrophoretic
      migration. In this paper, we use our previously published approach to decouple
      these two mechanisms via analysis of the input data for estimation of
      electrokinetic parameters, such as conductivity, equivalent lengths, mobilities
      and velocities. Separation of weakly retained, charged analytes was performed via
      voltage-assisted micro-HPLC. Contrary to conclusions from data analysis using the
      conventional definitions of the retention factor, it is shown that our approach
      allows us to isolate the "chromatographic retention" component and thus,
      investigate the "modification" of the retention process upon application of
      voltage in micro-HPLC. It is shown that the traditional approaches of calculating
      retention factor would erroneously lead to conclusion that the retention behavior
      of these analytes changes upon application of voltage. However, the approach
      suggested here demonstrates that under the conditions investigated, most of the
      charged analytes do not show any significant retention on the columns and that
      all the changes in their retention times can be attributed to their
      electrophoretic migration.

PMID- 16275299
TI  - Thirteen-year follow-up of a mandibular implant-supported fixed complete denture
      in a patient with Sjogren's syndrome: a clinical report.
AB  - This clinical report describes the treatment and long-term follow-up of a patient
      with Sjogren's syndrome treated with osseointegrated implants and a mandibular
      fixed complete denture. The implants and prosthesis have remained stable and
      functional for 13 years. Implant treatment may, therefore, offer a viable long
      term treatment alternative for patients with Sjogren's syndrome.

PMID- 16275300
TI  - Dentin exposure in tooth preparations for porcelain veneers: a pilot study.
AB  - STATEMENT OF PROBLEM: The various clinical techniques available for even
      reduction of a tooth surface to receive a porcelain veneer restoration do not
      produce a consistently even conservative reduction. In addition, it is not known
      which technique is most conservative of enamel. PURPOSE: The purpose of this
      pilot study was to assess the effectiveness of 3 clinical techniques, namely,
      dimple, depth groove, and freehand, in producing an intraenamel preparation. The
      relation between overpreparation beyond the commonly accepted depth of
      preparation of 0.5 mm and dentin exposure was also examined. MATERIAL AND
      METHODS: A single operator prepared 3 groups of 5 extracted maxillary central
      incisors to a depth of 0.5 mm using dimple, depth-groove, and freehand methods of
      tooth preparation. The prepared teeth were scanned using an x-ray microtomography
      scanner. The reconstructed images were studied using software that provided a
      volume-rendering routine so that, by choosing suitable x-ray linear attenuation
      coefficient thresholds, enamel (2.78 cm(-1) at 40 keV) and dentin (1.63 cm(-1) at
      40 keV) surfaces could be viewed. The percentage area of enamel conserved was
      analyzed from these images. Coordinate metrology was used to produce color-coded
      images depicting the depth of preparation. The Kruskal-Wallis test was used to
      determine the statistical significance (alpha=.05) in the difference between the
      mean percentage area of enamel conserved in the 3 technique groups. The
      coordinate metrology and x-ray microtomography images were visually compared to
      study the correlation between overpreparation and dentin exposure. RESULTS: The
      Kruskal-Wallis test did not demonstrate significant difference (P=.07) between
      the 3 techniques in conserving enamel. However, the dimple technique showed a
      greater trend to retaining a larger mean percentage area of enamel (77.5% +/-
      14.2) compared to depth-groove (50.1% +/- 17.5) and freehand (76.8% +/- 24.4)
      techniques. Preparation depth in the range of 0.4 to 0.6 mm was largely seen to
      be intraenamel, except in the cervical region. CONCLUSION: Within the limitations
      of this pilot study, the 3 different techniques tested did not differ
      significantly in conserving enamel.

PMID- 16275301
TI  - An evaluation of the effects of handpiece speed, abrasive characteristics, and
      polishing load on the flexural strength of polished ceramics.
AB  - STATEMENT OF PROBLEM: Many studies on the strengthening effects of grinding and
      polishing, as well as heat treatment on ceramics, are not well standardized or
      use commercially available industrial polishing systems. The reported
      effectiveness of these strengthening mechanisms on ceramics may not be applicable
      to clinical dentistry. PURPOSE: The purpose of this study was to evaluate the
      effects of controlled polishing on the flexural strength of dental ceramics by
      using a custom-made machine that applied standardized loads and speeds that
      coincided with the mean loads and speeds used by experienced prosthodontists.
      MATERIAL AND METHODS: A total of 140 aluminous dental ceramic bar-shaped
      specimens (Vitadur Alpha Enamel) measuring 1.5 x 2.0 x 25 mm were fabricated and
      divided into 12 groups (for most groups, n=10). Specimens were untreated,
      polished with different polishing systems, polished at different speeds, ground
      and autoglazed, polished and autoglazed, autoglazed and polished, polished with
      loose (paste) and bonded abrasives, or overglazed. Simulated clinical polishing
      was performed on the ceramic specimens by using a customized polishing apparatus
      that allowed independent control over the relevant polishing parameters (abrasive
      hardness, applied load, linear speed, rotational velocity, and wheel stiffness).
      Flexural strength (MPa) was measured with a 4-point bending test, and subjective
      surface roughness was assessed with scanning electron microscopy. Autoglazing was
      performed at various stages of the polishing sequence to determine the effects of
      polishing on surface stresses. Mean values, standard deviations, independent
      sample t tests, 1-way and 2-way analyses of variance, Dunnett t tests and Kruskal
      Wallis tests were applied to the data (alpha=.05). RESULTS: Under a clinical load
      of 0.6 N for a coarse polishing wheel, 1.0 N for a medium polishing wheel, and
      1.3 N for a fine polishing wheel, a linear speed of 499 mm/min, and a rotational
      velocity of 10,000 rpm, the use of clinical polishing instruments did not affect
      the flexural strength of the aluminous ceramics studied (P=.274). At higher
      rotational velocity (20,000 rpm), specimens polished with the diamond polishing
      system produced statistically weaker specimens compared with those that had been
      polished at 10,000 rpm (P=.019). Autoglazing treatment of the diamond-polished
      specimens did not reverse the strength degradation (P=.125). Conversely, diamond
      polishing of the autoglazed specimens resulted in significant flexural strength
      reduction (P=.029). Fine-diamond-bonded abrasive significantly reduced flexural
      strength (P=.025). CONCLUSIONS: Simulated clinical polishing at 10,000 rpm did
      not appear to substantially strengthen or weaken the ceramic specimens. Polishing
      at 20,000 rpm reduced flexural strength of the ceramic bars.

PMID- 16275302
TI  - Influence of recasting palladium-silver alloy on the fit of crowns with different
      marginal configurations.
AB  - STATEMENT OF PROBLEM: Dental laboratories may occasionally recast previously cast
      dental alloy to produce a prosthesis, but this process may have a negative
      influence on marginal adaptation. PURPOSE: The aim of this study was to evaluate
      the cervical and internal fit of complete metal crowns that were cast and recast
      using palladium-silver alloy and 3 different marginal configurations: straight
      shoulder, 20-degree bevel shoulder, and 45-degree chamfer. MATERIAL AND METHODS:
      Thirty aluminum dies were made, 10 for each marginal configuration. Each group of
      10 was further divided into 2 subgroups (n=5), according to the alloy (Pors-on 4)
      casting history. The dies were waxed using a cylindrical metal matrix to
      standardize the thickness of the walls. The wax patterns were invested in a
      phosphate-bonded investment (Deguvest) and cast after heating in an oven (EDG),
      according to the manufacturer's instruction. The alloy was melted with an oxygen
      gas heat source and cooled to room temperature after casting. Afterwards, the
      specimens were seated on the dies with a static load of 9 kgf for 1 minute. The
      marginal discrepancy was measured with a metric microscope, using a digital
      micrometer. All the measurements were done by the same operator. Each crown-die
      interface was measured 3 times on each of the 4 diametrically opposite points,
      for a total of 12 measurements for each specimen. Specimens were longitudinally
      sectioned to obtain 2 hemi-sections for internal discrepancy measurements,
      measured at 3 points: 1 in the center of the occlusal wall and 2 at each center
      of each axial wall. Three measurements were made for each point, for a total of 9
      measurements per specimen. The results were submitted to parametric statistical 3
      way analysis of variance followed by Tukey-Kramer HSD post hoc analysis
      (alpha=.05). RESULTS: The new alloy provided significantly better adaptation
      (P<.001) than the recast alloy for both marginal and internal discrepancy
      measurements. Marginal designs did not shown any statistical differences when the
      new metal was used. For recast metal, the straight shoulder showed significantly
      better adaptation (P<.001) than the 20-degree bevel shoulder and the 45-degree
      chamfered configurations, which were statistically similar to each other.
      CONCLUSION: The results of this study suggest that recasting procedures for crown
      fabrication should not be used with the palladium-silver alloy tested.

PMID- 16275303
TI  - Effect of soldering on the metal-ceramic bond strength of an Ni-Cr base alloy.
AB  - STATEMENT OF PROBLEM: Although soldering is a common laboratory procedure, the
      use of soldering alloys may adversely affect metal-ceramic bond strength and
      potentially decrease the longevity of metal-ceramic restorations. PURPOSE: The
      purpose of this study was to investigate the effect of soldering on metal-ceramic
      bond strength of a representative Ni-Cr base metal alloy. MATERIAL AND METHODS:
      Twenty-eight rectangular (25 x 3 x 0.5 mm) Ni-based alloy (Wiron 99) specimens
      were equally divided into soldering (S) and reference (R) groups. Soldering group
      specimens were covered with a 0.1-mm layer of the appropriate solder (Wiron-Lot)
      and reduced by 0.1 mm on the opposite side. Five specimens of each group were
      used for the measurement of surface roughness parameter (R(z)) and hardness, and
      3 were used for measurement of the modulus of elasticity. Six specimens of each
      group were covered with porcelain (Ceramco 3) and subjected to a 3-point bending
      test for evaluation of the metal-ceramic bond strength according to the ISO 9693
      specification. The data from surface roughness, hardness, modulus of elasticity,
      and metal-ceramic bond strength were analyzed statistically, using independent t
      tests (alpha=.05). RESULTS: Statistical analysis of the R(z) surface roughness
      parameter (S: 3.4 +/- 0.3 mum; R: 3.7 +/- 0.7 microm; P=.07) and bond strength
      (S: 46 +/- 3 MPa; R: 40 +/- 5 MPa; P=.057) failed to reveal any significant
      difference between the 2 groups. The specimens of the soldering group
      demonstrated significantly lower values both in hardness (S: 128 +/- 11 VHN; R:
      217 +/- 4 VHN; P<.001) and in modulus of elasticity (S: 135 +/- 4 GPa; R: 183 +/-
      6 GPa; P=.035) than the reference group. CONCLUSION: Under the conditions of the
      present study, the addition of solder to the base metal alloy did not affect the
      metal-ceramic bond strength.

PMID- 16275304
TI  - Factors affecting soft tissue around dental implants: a review of the literature.
AB  - Much of the focus in the early dental implant literature is on the bone-to
      titanium interface because a successful osseointegrated implant requires direct
      bone contact to the implant surface. The research on soft tissue around dental
      implants has focused on the partially edentulous patient and, in particular, on
      the maxillary anterior dentition. Few studies have evaluated soft tissue around
      dental implants in completely edentulous patients over time. This paper reviews
      the pertinent literature on soft-tissue healing in both partially and completely
      edentulous dental implant patients from a Medline search of the English peer
      reviewed literature from 1980 to 2004.

PMID- 16275305
TI  - Evaluation of adhesion of chairside hard relining materials to denture base
      polymers.
AB  - STATEMENT OF PROBLEM: Removable denture bases are made of modified poly(methyl
      methacrylate) (PMMA), which has reliable bond strength with resins containing
      methyl methacrylate (MMA). However, some hard relining materials with different
      chemical compositions have been reported to have less than adequate bond strength
      to PMMA denture base polymers. PURPOSE: This in vitro study evaluated the initial
      bonding properties of chairside hard relining materials to different removable
      denture base polymers, as well as the structure of the interface. MATERIAL AND
      METHODS: The tensile strength (MPa) of adhesion of 8 chairside hard relining
      materials (Original Truliner, GC Reline Hard, Ufigel Hard, Triad Reline, New
      Truliner, Light Liner, Astron LC Hard, and Flexacryl Hard) was tested against 3
      denture base polymers (Ivocap Plus, Paladon 65, and Palapress Vario). Dumbbell
      shaped specimens with a 6-mm diameter of bonding surface were used for tensile
      testing of bond strength (n=5). An MMA containing hard relining material
      (Original Truliner) was used as a control. Tensile strength of the bond was
      calculated using the bonding area and maximum force under tension. Statistical
      analyses of data were conducted with 2-way analysis of variance (alpha=.05). The
      influence of the bonding agents and the relining materials on the PMMA denture
      base surface layer and its structure were investigated. The depths of the swollen
      layers were measured with a transmission light microscope. Fracture surfaces
      after testing were also visually evaluated. Chemical analyses of all materials
      prior to testing were performed using high-performance liquid chromatography.
      RESULTS: Significant differences were found among tensile bond strengths of
      chairside hard relining materials to PMMA denture base polymers forming 3
      different groups (P<.001). No significant difference among different denture base
      polymers was found with regard to tensile strength of adhesion (P=.918), but the
      interaction term between hard relining material and denture base polymer was
      found to be significant (P<.001). The tensile bond strength of the relining
      materials and denture base polymers was found to range from 8% to 60% of the
      strength of the PMMA denture base polymers. CONCLUSION: The chemical composition
      of the bonding agents and the relining materials and their combinations affected
      the depth of the swollen layers of the denture base polymers and the tensile
      strength of adhesion.

PMID- 16275306
TI  - In vitro wear resistance of three types of composite resin denture teeth.
AB  - STATEMENT OF PROBLEM: The wear resistance of artificial teeth is important to the
      life of the removable prosthesis for the edentulous patient. The ability of
      artificial teeth to maintain a stable occlusal relationship over time may be
      influenced by this property. PURPOSE: The purpose of this in vitro study was to
      evaluate the wear resistance of artificial teeth based on composite resin filler
      content when opposed by a denture tooth antagonist. MATERIAL AND METHODS: The
      right first molars (both maxillary and mandibular) of 3 composite resin denture
      teeth (Endura, 47% organic filler; Duradent, 42% organic and inorganic filler;
      and Duracross, 68% organic filler) were secured in an in vitro 2-body wear
      testing apparatus that simulated masticatory function (60 strokes/min, grinding
      distance of 2 mm, under 37 degrees C flowing water). Wear resistance was assessed
      as volume loss (mm3) and height loss (mm) at 5 kgf (grinding force) after 50,000
      strokes (6 pairs for each type). The Vickers microhardness (VHN) of the occlusal
      surfaces was measured with a load of 50 g and a loading time of 30 seconds. After
      testing, the worn surfaces were observed with a scanning electron microscope
      (SEM). Mean values were analyzed using a 1-way analysis of variance followed by
      the Fisher test (alpha=.05). RESULTS: The volume loss of Duradent teeth (0.87 +/-
      0.03 mm3) was significantly higher than of the 2 other types of teeth tested
      (P<.001). The Duracross teeth (0.22 +/- 0.08 mm3 and 0.11 +/- 0.04 mm) exhibited
      the best wear resistance of the denture teeth tested. The wear resistance of the
      materials tested was consistent with their hardness (Endura 27.54 +/- 0.67 VHN,
      Duradent 24.00 +/- 0.60 VHN, Duracross 39.64 +/- 3.11 VHN). SEM observation
      showed that many filler particles were missing from the matrix of Duradent.
      CONCLUSION: The wear resistance among the 3 types of teeth was significantly
      different; Duracross and Endura were more wear resistant than Duradent. Although
      the densities as reported by the manufacturer were similar, hardness and
      microstructure were the primary factors affecting the wear resistance of
      artificial teeth. Hardness appears to correlate with wear resistance since the
      wear resistance of Duradent with a lower VHN of 24 was greater than the other 2
      types of teeth with greater hardness.

PMID- 16275307
TI  - Reliability of recording static and dynamic occlusal contact marks using
      transparent acetate sheet.
AB  - STATEMENT OF PROBLEM: Inaccuracy in the transfer of information between clinician
      and technician regarding occlusal contacts can cause problems when fabricating
      indirect restorations, which can result in frustration for the dentist,
      technician, and patient. Few studies have considered the reproducibility of
      recording marked occlusal contacts. PURPOSE: This study aimed to test the
      reproducibility of a quick and simple means of recording marked occlusal
      contacts. MATERIAL AND METHODS: The static and dynamic occlusal contacts of 29
      subjects, with no missing functional units, were marked using articulating paper.
      Three clinicians with varying clinical experience (3-10 years after graduation
      from dental school) were asked to independently record the marked occlusal
      contacts using a transparent acetate sheet. The results were analyzed for Kappa
      agreement. RESULTS: For the static occlusion, Kappa values of agreement between
      pairs of examiners were 0.88, 0.86, and 0.85, respectively, all indicating
      "almost perfect agreement." For the dynamic occlusion, the range of Kappa
      agreement between pairs of examiners produced a median of 0.91, 0.88, and 0.85,
      respectively, indicating almost perfect strength of agreement. CONCLUSIONS: The
      results suggest that marking occlusal contacts on a transparent acetate sheet
      provides a simple means of recording static and dynamic occlusal contacts with a
      high degree of reproducibility.

PMID- 16275308
TI  - Construction of a surgical stent for posttraumatic nasal synechia.
AB  - This article describes the clinical and laboratory procedures for the
      construction of a surgical stent for prevention of restenosis after the surgical
      opening of posttraumatic synechia of the posterior part of the nasal cavum.

PMID- 16275309
TI  - Stable accelerometer attachment to the skin surface.

PMID- 16275310
TI  - A simplified custom impression technique.

PMID- 16275312
TI  - Fabrication of a metal-ceramic fixed partial denture using the prosthetic
      components of an unidentified implant system.

PMID- 16275311
TI  - Use of light-polymerized composite resin to stabilize ball attachments during
      transfer procedures.

PMID- 16275314
TI  - High-level expression and purification of recombinant E1 enzyme.
AB  - The ubiquitin E1 enzyme is an ATP-dependent enzyme that activates ubiquitin for
      use in all ubiquitin conjugation pathways. This chapter describes the expression
      and purification of human E1 enzyme for use in in vitro ubiquitination reactions.

PMID- 16275315
TI  - Expression, purification, and characterization of the E1 for human NEDD8, the
      heterodimeric APPBP1-UBA3 complex.
AB  - The NEDD8 pathway is important for numerous biological processes, including cell
      proliferation, signal transduction, and development. The heterodimeric activating
      enzyme of NEDD8, APPBP1-UBA3, plays an essential role in NEDD8 conjugation. Not
      surprisingly, mutations in APPBP1 and UBA3 lead to defects in many cellular
      functions. The APPBP1-UBA3 complex initiates NEDD8 conjugation by first
      catalyzing adenylation of the C terminus of NEDD8 and ultimately catalyzing
      transfer of NEDD8 to the downstream enzyme in the pathway, Ubc12. This chapter
      describes methods for expressing and purifying APPBP1-UBA3 for in vitro studies
      of NEDD8 conjugation.

PMID- 16275316
TI  - A fluorescence resonance energy transfer-based assay to study SUMO modification
      in solution.
AB  - Analysis of posttranslational modifications with ubiquitin and ubiquitin-related
      proteins (Ubl) generally involves detection of the modified species by
      immunoblotting or autoradiography, techniques that are not easily applicable for
      kinetic, quantitative, or high-throughput assays. To circumvent these limitations
      for studies on ubiquitin-related proteins of the SUMO family, we have developed a
      fluorescence resonance energy transfer (FRET)-based assay system using yellow
      fluorescent protein (YFP)-tagged mature SUMO1 (amino acids 1-97) and cyan
      fluorescent protein (CFP)-tagged RanGAP1 (amino acids 400-589) as model
      substrates. Reactions are set up in 384-well microtiter plates and are followed
      online using a fluorescence microtiter plate reader. Applications may involve
      identification and analysis of SUMO-modifying enzymes and isopeptidases,
      comparison of enzyme and substrate mutants, and screens for small molecular
      weight inhibitors. The principal outline of the assay should be applicable to
      other Ubl conjugation systems as well.

PMID- 16275317
TI  - Properties of the ISG15 E1 enzyme UbE1L.

PMID- 16275318
TI  - Purification and properties of the ubiquitin-conjugating enzymes Cdc34 and
      Ubc13.Mms2.
AB  - A prerequisite for structure/function studies on the ubiquitin-conjugating
      enzymes (Ubc) Cdc34 and Ubc13.Mms2 has been the ability to express and purify
      recombinant derivatives of each. This chapter describes the methods used in the
      expression and purification of these proteins from Escherichia coli, including
      variations of these protocols used to generate (35)S, (15)N, (13)C/(15)N, and
      seleno-L-methionine derivatives. Assays used to measure the Ub thiolester and Ub
      conjugation activities of these Ubcs are also described.

PMID- 16275319
TI  - Expression, purification, and properties of the Ubc4/5 family of E2 enzymes.
AB  - Ubiquitin-conjugating enzymes (E2s) play a central role in ubiquitylation. They
      function to bridge the first, nonspecific step of ubiquitin activation by E1 with
      the transfer of activated ubiquitin to substrates by substrate-specific E3s.
      While sharing a common core UBC domain, members of this family exhibit
      significant specificity in their physical and functional interactions with E3s.
      Among the families of E2s, members of the yeast Ubc4/5 family are particularly
      well conserved in higher metazoans. In humans, these are represented by the UbcH5
      family. Members of this ubiquitously expressed family show a capacity to interact
      with a wide range of E3s from both HECT and RING finger families, making them
      particularly useful tools in the laboratory. Using the UbcH5 family as a
      prototype, this chapter describes methods for the expression, purification, and
      characterization of E2 enzymes in vitro and some of the basics for their use in
      experiments in cells.

PMID- 16275320
TI  - In vitro systems for NEDD8 conjugation by Ubc12.
AB  - Nedd8 is a ubiquitin-like molecule that is highly conserved in eukaryotes.
      Similar to ubiquitin, Nedd8 attaches to target proteins through an enzymatic
      cascade composed of Nedd8-specific E1 (activating)- and E2 (conjugating)-enzymes.
      The E1 for Nedd8 is a heterodimer of APP-BP1 and Uba3, while the E2 is Ubc12. The
      most well-characterized targets of Nedd8 are proteins of the Cullin family, a
      core component of SCF (Skp1/Cullin1/F-box proteins) and/or SCF-like ubiquitin
      ligase complexes. The Nedd8 modification of Cullin (Cul) family proteins is
      evolutionarily conserved, and genetic analyses in various organisms suggest a
      positive role of the NEDD8 for the function of Cul family proteins. Further
      biochemical analysis reveals that NEDD8 modification augments the ubiquitin
      ligase activity of Cullin-based complexes through the recruitment of ubiquitin
      charged E2 to the complex. This chapter describes methods for the purification of
      NEDD8 conjugation enzymes and in vitro Nedd8 conjugation.

PMID- 16275321
TI  - Purification and activity assays for Ubc9, the ubiquitin-conjugating enzyme for
      the small ubiquitin-like modifier SUMO.
AB  - The small ubiquitin-like modifier (SUMO) can be conjugated to lysine residues
      directly by the ubiquitin-conjugating protein Ubc9. SUMO conjugation can be
      catalyzed in vitro using only E1, Ubc9 (E2), mature SUMO, and ATP because Ubc9
      directly recognizes consensus SUMO modification sites found in many identified
      targets of SUMO conjugation. This article describes methods to prepare Ubc9 and
      provides details for assay conditions used to evaluate E2 thioester formation and
      E2-mediated SUMO conjugation under single turnover and multiple turnover
      conditions. It also briefly describes parameters used to evaluate E3-mediated
      SUMO conjugation. Conservation of the SUMO conjugation apparatus from yeast to
      human has enabled in vivo assessment of human Ubc9 function through yeast
      complementation assays.

PMID- 16275322
TI  - High-throughput assay to monitor formation of the E2-ubiquitin thioester
      intermediate.
AB  - Targeting components of ubiquitination pathways for drug discovery necessitates
      the development of high-capacity assays that monitor the ubiquitination process
      at defined steps of the E1-E2-E3 cascade. This chapter describes the development
      of an assay based on time-resolved fluorescence to monitor formation of the
      thioester intermediate between ubiquitin-conjugating enzymes (E2s) and ubiquitin.
      The methodology is exemplified by an assay tailored for the ubiquitin-conjugating
      enzyme Cdc34. This assay setup can be easily adapted to other E2s and is suitable
      to screen small molecule inhibitors of E2-thioester formation in a high
      throughput mode.

PMID- 16275323
TI  - Expression and evaluation of RING finger proteins.
AB  - RING finger proteins represent the largest class of potential ubiquitin ligases.
      This chapter describes methods used to express and assess the activity of
      proteins containing RING fingers based on our experience with a number of
      different family members. In addition to general protocols for assessing
      activity, specific protocols are provided for evaluating the ubiquitylation of
      p53 by the RING finger E3 Hdm2/Mdm2. Use of these methods may help identify new
      E3s, dissect factors involved in ubiquitylation of substrates, and screen for
      molecules that affect ubiquitylation.

PMID- 16275324
TI  - Expression and assay of HECT domain ligases.
AB  - HECT domain ubiquitin ligases (HECT E3s), typified by human E6AP and yeast Rsp5p,
      are unique among the several classes of known ubiquitin ligases in that they
      participate directly in the chemistry of substrate ubiquitination reactions. This
      chapter discusses strategies for the expression of active HECT E3s and the assays
      that are available for analyzing E2 interaction, ubiquitin-thioester formation,
      and substrate ubiquitination.

PMID- 16275326
TI  - In vitro reconstitution of SCF substrate ubiquitination with purified proteins.
AB  - The development of in vitro systems to monitor ubiquitin ligase activity with
      highly purified proteins has allowed for new insights into the mechanisms of
      protein ubiquitination to be uncovered. This chapter describes the methodologies
      employed to reconstitute ubiquitination of the budding yeast cyclin-dependent
      kinase inhibitor Sic1 by the evolutionarily conserved ubiquitin ligase SCF(Cdc4)
      and its ubiquitin-conjugating enzyme Cdc34. Based on our experience in
      reconstituting Sic1 ubiquitination, we suggest some parameters to consider that
      should be generally applicable to the study of different SCF complexes and other
      ubiquitin ligases.

PMID- 16275325
TI  - High-level expression and purification of recombinant SCF ubiquitin ligases.
AB  - The SCF complexes are the prototype of a superfamily of cullin-dependent
      ubiquitin ligases, which regulate diverse cellular functions by promoting the
      ubiquitination of a large number of regulatory and signaling proteins. The SCF
      complexes are organized by the elongated scaffold protein subunit Cul1, which
      interacts with the Rbx1 RING finger protein at one end and the Skp1 adaptor
      protein at the other. By binding to Skp1, members of the F-box protein family are
      responsible for recruiting specific substrates to the ligase machine. This
      chapter describes methods that we have developed to achieve high-level expression
      and purification of two recombinant SCF complexes from both insect cells and
      bacteria. We emphasize the power of protein coexpression and a novel "Split-n
      Coexpress" method in producing soluble and functional recombinant proteins and
      protein complexes. We propose that similar approaches can be used to obtain large
      quantities of other SCF and SCF-like complexes for biochemical and structural
      investigations.

PMID- 16275327
TI  - Expression and assay of glycoprotein-specific ubiquitin ligases.
AB  - N-linked glycosylation of proteins that takes place in the endoplasmic reticulum
      (ER) plays a key role in protein quality control. Misfolded proteins or
      unassembled protein complexes that fail to achieve their functional states in the
      ER are retrotranslocated into the cytosol and degraded by the ubiquitin
      proteasome system in a process called ER-associated degradation (ERAD). N-linked
      glycoprotein-specific ubiquitin ligase complexes, SCF(Fbs1) and SCF(Fbs2), appear
      to participate in ERAD for selective elimination of aberrant glycoproteins in the
      cytosol. This chapter describes methods employed for the isolation and
      oligosaccharide-binding assay of Fbs proteins that are the substrate-recognition
      components of the SCF(Fbs) complex and the in vitro ubiquitylation assay of the
      SCF(Fbs) ubiquitin ligase complexes.

PMID- 16275328
TI  - Affinity purification of mitotic anaphase-promoting complex/cyclosome on p13Suc1.
AB  - A procedure is described for the affinity purification of the mitotic form of
      anaphase-promoting complex/cyclosome (APC/C) from HeLa cells. It is based on the
      binding of mitotically phosphorylated APC/C to the phosphate-binding site of
      p13(suc1), followed by specific elution with a phosphate-containing compound. The
      procedure is rapid, simple, and yields 50- to 70-fold purification of soluble
      APC/C, with a approximately 30% recovery of activity.

PMID- 16275329
TI  - Large-scale purification of the vertebrate anaphase-promoting complex/cyclosome.
AB  - The anaphase-promoting complex or cyclosome (APC/C) is a ubiquitin ligase that
      controls progression through mitosis and the G1 phase of the cell cycle. The
      APC/C is a 1.5-MDa complex composed of at least 12 different core subunits. At
      different stages of mitosis and G1, the APC/C associates with a variety of
      regulatory proteins, such as the activator proteins Cdc20 and Cdh1 and the
      mitotic checkpoint complex (MCC), which regulate APC/C activity in a substrate
      specific manner. Although APC/C and its regulators have been under intense
      investigation, it is still poorly understood how substrates are recognized and
      ubiquitinated by the APC/C, why so many subunits are required for these
      processes, and how regulators of the APC/C control its ubiquitin ligase activity
      in a substrate-specific manner. This chapter describes a simple and rapid
      procedure that allows the isolation of APC/C from vertebrate cells and tissues
      with reasonable purity and at high concentrations, yielding up to 0.5 mg of
      APC/C. This procedure should facilitate biochemical, biophysical, and structural
      analyses of the APC/C that will be needed for a better mechanistic understanding
      of its function and regulation.

PMID- 16275330
TI  - Purification and assay of the budding yeast anaphase-promoting complex.
AB  - The anaphase-promoting complex (APC) is a central regulator of the eukaryotic
      cell cycle and functions as an E3 ubiquitin protein ligase to catalyze the
      ubiquitination of a number of cell cycle regulatory proteins. The APC contains at
      least 13 subunits in addition to two activator subunits, Cdc20 and Cdh1, that
      associate with the APC in a cell cycle-dependent manner. This chapter describes
      methods for preparation and assay of the APC from Saccharomyces cerevisiae.
      Highly active APC is purified from cells expressing Cdc16 fused with a tandem
      affinity purification (TAP) tag. Enzymatically active APC is achieved upon
      addition of recombinant Cdc20 or Cdh1 together with E1, Ubc4, ATP, and ubiquitin.
      Activity assays toward several endogenous substrates, including Clb2 and Pds1,
      are described. In addition, methods for observation of APC-coactivator and APC
      substrate complexes by native gel electrophoresis are described.

PMID- 16275331
TI  - Enzymology of the anaphase-promoting complex.
AB  - The anaphase-promoting complex (APC) is an ubiquitin-protein ligase that promotes
      mitotic progression by catalyzing the ubiquitination of numerous proteins,
      including securin and cyclin. Its complex subunit composition and extensive
      regulation make the APC an active subject of investigation for both cell
      biologists and enzymologists. This chapter describes a system for the
      reconstitution and quantitative analysis of APC activity from budding yeast in
      vitro. We focus in particular on the measurement of processive ubiquitination,
      which complements traditional analysis of the reaction rate as a means to
      elucidate the molecular details of substrate recognition and ubiquitination by
      the APC.

PMID- 16275332
TI  - Identification of cell cycle-dependent phosphorylation sites on the anaphase
      promoting complex/cyclosome by mass spectrometry.
AB  - Phosphorylation has an almost universal role in controlling the properties of
      proteins that govern progression through mitosis and meiosis. The ubiquitin
      ligase anaphase-promoting complex/cyclosome (APC/C) and its cofactors are no
      exception to this rule. However, it is poorly understood how APC/C pathway
      components are regulated by phosphorylation, i.e., little is known about which
      amino acid residues on subunits and regulators of the APC/C are phosphorylated by
      which kinase, when during the cell cycle, where in the cell, and with which
      functional consequence. As a first step toward answering these questions we have
      established a procedure for the sensitive and relatively rapid identification of
      phosphorylation sites on small microgram amounts of the APC/C and on associated
      regulatory proteins. This procedure will enable studies on the dynamic changes of
      APC/C phosphorylation during the cell cycle and, in conjunction with chemical
      biology approaches, will allow one to determine which phosphorylation sites
      depend on the presence of which kinase activity in living cells.

PMID- 16275333
TI  - Purification and assay of Mad2: a two-state inhibitor of anaphase-promoting
      complex/cyclosome.
AB  - To maintain the fidelity of chromosome inheritance, cells utilize a surveillance
      mechanism called the spindle checkpoint to sense improper attachment of sister
      chromatids to the mitotic spindle prior to chromosome segregation. The target of
      the spindle checkpoint is a ubiquitin ligase called the anaphase-promoting
      complex or cyclosome (APC/C). The spindle checkpoint protein Mad2 inhibits the
      activity of APC/C through direct binding to its activator Cdc20. Studies have
      shown that Mad2 has two distinct natively folded conformations and that the
      unusual two-state behavior of Mad2 plays a crucial role in checkpoint signaling.
      This article describes methods for the purification of the two Mad2 conformers
      and for the analysis of their activities in APC/C inhibition in Xenopus egg
      extracts.

PMID- 16275334
TI  - Identification, expression, and assay of an oxidation-specific ubiquitin ligase,
      HOIL-1.
AB  - The ubiquitin system plays important roles in the regulation of numerous cellular
      processes. It is well established that ubiquitin ligases (E3s) are key components
      in determining the specificity of the system and that the modification of
      substrates such as phosphorylation often plays a critical role in selective
      substrate recognition by E3s. Through studies analyzing iron-mediated degradation
      of iron regulatory protein 2 (IRP2), a central regulator of iron metabolism in
      mammalian cells, we have identified a RING finger protein, HOIL-1, as an
      ubiquitin ligase recognizing IRP2 through a signal created by heme-mediated
      oxidative modification of the protein. We have utilized several types of in vitro
      ubiquitination assays that detect IRP2 ubiquitination and a differential yeast
      two-hybrid screen in which yeast cells were cultured either in the presence or in
      the absence of oxygen to control the oxidation state of the bait in the cells in
      our studies. This chapter describes the detailed methods used for the
      identification and functional analysis of the HOIL-1 ligase.

PMID- 16275335
TI  - Purification and assay of the chaperone-dependent ubiquitin ligase of the
      carboxyl terminus of Hsc70-interacting protein.
AB  - It is notable that both chaperone and ubiquitin-proteasome systems are required
      for the removal of aberrant cellular proteins to ensure protein homeostasis in
      cells. However, the entity that links the two systems had remained elusive. The
      carboxyl terminus of Hsc70-interacting protein (CHIP), originally identified as a
      cochaperone of Hsc70, has both a TPR motif and a U-box domain. The TPR motif
      associates with Hsp70 and Hsp90, whereas the U-box domain executes ubiquitin
      ligase activity. Thus, CHIP is an ideal molecule, acting as a protein quality
      control ubiquitin ligase that selectively leads abnormal proteins recognized by
      molecular chaperones to degradation by the proteasome. This chapter describes
      methods of analyzing chaperone-dependent ubiquitin ligase activity of CHIP using
      firefly luciferase as a model substrate.

PMID- 16275336
TI  - Methods for the functional genomic analysis of ubiquitin ligases.
AB  - Ubiquitin ligases (E3s) are critical components of the ubiquitin-proteasome
      system as they are the major determinants of specificity in ubiquitin
      conjugation. The number of predicted E3s in the mammalian genome is exceeding 400
      and is represented by two major subfamilies: HECT domain-containing E3s and RING
      finger-type E3s. Given the size of this protein family and lack of knowledge on
      the functions of most of these 400 proteins, their functional annotation should
      benefit from modern genomic tools. This article presents a methodology consisting
      of the use of a cDNA expression library to identify suppressors of polyglutamine
      (polyQ)-mediated protein aggregate formation in cells, as an example of a genomic
      approach to assign functions to E3s. In this screen, we identified novel RING
      finger-type E3s exhibiting suppressor activity among >50% of all the potential
      E3s in the mouse and human genomes. This method could be adapted easily to
      identify E3s that function in other processes and signaling pathways.

PMID- 16275337
TI  - Purification of PA700, the 19S regulatory complex of the 26S proteasome.
AB  - The 26S proteasome is a 2,400,000-Da protease complex that selectively degrades
      proteins modified by polyubiquitin chains. The 26S proteasome is composed of two
      700,000-Da multisubunit complexes: the 20S proteasome, which serves as the
      proteolytic core of the complex, and PA700, an ATPase regulatory complex
      responsible for the binding, modification, and delivery of substrates to the
      proteolytic chamber. Thus, PA700 mediates multiple functions essential for
      ubiquitin-dependent proteolysis by the 26S proteasome. This chapter reviews
      briefly the structure and function of PA700, details the methodology for its
      large-scale purification from mammalian tissues, and describes a simple
      functional PA700 assay based on the stimulation of proteasome activity.

PMID- 16275338
TI  - Purification and analysis of recombinant 11S activators of the 20S proteasome:
      Trypanosoma brucei PA26 and human PA28 alpha, PA28 beta, and PA28 gamma.
AB  - Proteasomes perform the bulk of nonlysosomal degradation of aberrant, damaged,
      misfolded, and naturally short-lived regulatory proteins in eukaryotic cells.
      They are approximately 700-kDa assemblies whose hollow architecture sequesters
      the proteolytic sites inside a central chamber, thereby ensuring that the
      activity of isolated proteasomes is repressed. In vivo, proteasomes are activated
      by protein complexes, including the 11S activators (PA28 and PA26), which bind to
      one or both ends of the barrel-shaped structure. This chapter describes protocols
      for the purification of recombinant 11S regulators, characterization of their
      ability to stimulate proteasome activity, and crystallization of proteasome
      complexes.

PMID- 16275339
TI  - Purification and assay of proteasome activator PA200.
AB  - PA200, the most recently discovered activator of the 20S proteasome, is a nuclear
      protein thought to play a role in DNA repair. Homologs of PA200 have been found
      in rat, frog, birds, worms, and budding yeast, where it is called Blm3p (now
      known as Blm10p), but not in Drosophila or fission yeast. Western blots of SDS
      PAGE transfers reveal 160 and 200K forms of mammalian PA200, and organ surveys
      demonstrate that the 200K species is highest in testis. PA200 purified from
      bovine testis binds the ends of the cylindrical 20S proteasome, forming volcano
      shaped structures in negatively stained EM images. In vitro assays demonstrate
      that binding of PA200 activates peptide hydrolysis by the 20S proteasome. This
      chapter describes the purification and assay of bovine testis PA200.

PMID- 16275340
TI  - Purification, crystallization, and X-ray analysis of the yeast 20S proteasome.
AB  - Intracellular protein degradation is one of the most precisely regulated
      processes in living cells. The main component of the degradation machinery is the
      20S proteasome present in eukaryotes as well as in prokaryotes. We have developed
      successful purification protocols for the 20S proteasome in its native state
      using an affinity tag strategy. This chapter describes in detail the purification
      protocols, proteolytic activity assays, crystallization, and structure
      determination for the yeast 20S proteasome. The crystal structure of the
      eukaryotic proteasome opens new possibilities for identifying, characterizing,
      and elucidating the mode of action for natural and synthetic inhibitors, which
      affect its function. Some of these compounds may find therapeutic applications in
      contemporary medicine.

PMID- 16275341
TI  - Preparation of hybrid (19S-20S-PA28) proteasome complexes and analysis of
      peptides generated during protein degradation.
AB  - PA28 (also named REG or 11S) is a ring-shaped (180-kDa) interferon-gamma-induced
      complex that associates with the 20S proteasome and dramatically stimulates the
      breakdown of short peptides. Immunoprecipitation studies indicate that in vivo
      PA28 also exists in larger complexes that also contain the 19S particle, which is
      required for the ATP-ubiquitin-dependent degradation of proteins. However,
      because of its lability (e.g., it does not withstand exposure to high ionic
      strength buffers), this larger complex cannot be purified by standard biochemical
      protocols. Therefore, we developed a method to reconstitute in vitro such hybrid
      proteasomes (i.e., PA28-20S-19S) from highly purified components. This chapter
      describes conditions that allow the association of PA28 with "singly capped" 26S
      (i.e., 19S-20S) particles. In addition assays are described to measure absolute
      rates of degradation of several non-ubiquitinated proteins by 26S and 20S
      proteasomes and methods to analyze the pattern and size distribution of peptides
      generated during the degradation of these proteins.

PMID- 16275342
TI  - Characterization of the proteasome using native gel electrophoresis.
AB  - Several features of the proteasome make it an excellent subject for analysis by
      native gel electrophoresis: its size, the multiplicity of variant complexes
      having proteasome activity, the ease of in-gel assays for proteasome activity,
      and even its relatively high cellular abundance. Accordingly, native gels have
      been used to analyze the composition, assembly, gating activity, and binding
      characteristics of the proteasome. This chapter describes methods for preparing,
      running, and developing native gels and the proteasome species that are routinely
      visualized. Additionally, the use of native gels to resolve proteasome complexes
      present in lysate and to characterize proteasome ligands are described. Following
      native gel electrophoresis, secondary analyses can be performed, such as
      activating the core particle, making specific activity assessments, Western
      blotting of the native gel, resolving native complexes with subsequent SDS-PAGE,
      and protein identification by mass spectrometry.

PMID- 16275343
TI  - Monitoring activity and inhibition of 26S proteasomes with fluorogenic peptide
      substrates.
AB  - Eukaryotic proteasomes have three different types of active sites: two
      chymotrypsin-like, two trypsin-like, and two caspase-like (also termed PGPH)
      sites that differ in their specificity toward model fluorogenic peptide
      substrates. The chymotrypsin-like site is often considered the most important in
      protein breakdown, and the only one whose activity has to be assayed in order to
      assess the capacity of proteasomes to degrade proteins. However, recent results
      indicate that either trypsin-like or caspase-like sites also have to be inhibited
      in order to reduce breakdown of most proteins by 50%. Thus, the activities of all
      three types of active sites have to be assayed in order to evaluate the state of
      the proteasome inside cells or the potency of inhibitors. This chapter describes
      assays of purified 26S proteasomes with fluorogenic peptide substrates, including
      new substrates of the caspase- and trypsin-like sites. A novel assay of
      proteasome activity in crude cell extracts that allows rapid evaluation of the
      state of the proteasomes in cells treated with inhibitors is also described.

PMID- 16275344
TI  - The synthesis and proteasomal degradation of a model substrate Ub5DHFR.
AB  - The importance of substrate polyubiquitination in protein degradation has been
      established for many years. However, the many intricacies of substrate
      recognition and ubiquitination by E3 enzymes have greatly limited access to
      degradable substrate in vitro. Thus, detailed analysis of protein degradation
      using purified 26S proteasomes has been difficult. The ability to synthesize
      polyubiquitin chains in a test tube has provided a method to make large
      quantities of a specific polyubiquitinated substrate, Ub(5)DHFR. This chapter
      focuses on the synthesis and degradation of this model substrate.

PMID- 16275345
TI  - Assaying degradation and deubiquitination of a ubiquitinated substrate by
      purified 26S proteasomes.
AB  - The 26S proteasome is a multisubunit complex that catalyzes ATP-dependent
      proteolysis of cellular proteins. It eliminates misfolded proteins, as well as
      labile regulatory proteins, thereby serving a central role in maintaining
      cellular homeostasis. The bulk of the known substrates of the 26S proteasome are
      earmarked for proteolysis by covalent modification with a multiubiquitin chain,
      which is recognized by specific receptors. Once targeted, the substrate is
      deubiquitinated and degraded by the 26S proteasome. This chapter describes assays
      that monitor ATP- and ubiquitin-dependent proteolysis of the S-Cdk inhibitor
      Sic1.

PMID- 16275346
TI  - Probing the ubiquitin/proteasome system with ornithine decarboxylase, a ubiquitin
      independent substrate.
AB  - Ornithine decarboxylase (ODC) is an unusual proteasome substrate-ubiquitin
      conjugation plays no part in its turnover. It can therefore be used as a probe to
      distinguish proteasome-mediated actions that do or do not depend on the activity
      of the ubiquitin system. A 37 residue region of ODC suffices for proteasome
      interactions, and within this sequence functionally critical residues have been
      identified. Because no posttranslational modifications are required for substrate
      preparation, ODC and derived constructs can be readily generated as substrates
      for either in vitro or in vivo studies. This chapter describes methodologies that
      allow the use of ODC as a reporter to examine the ubiquitin-proteasome system,
      both in reconstituted in vitro systems and in living cells.

PMID- 16275347
TI  - Atomic force microscopy of the proteasome.
AB  - The proteasome should be an ideal molecule for studies on large enzymatic
      complexes, given its multisubunit and modular structure, compartmentalized
      design, numerous activities, and its own means of regulation. Considering the
      recent increased interest in the ubiquitin-proteasome pathway, it is surprising
      that biophysical approaches to study this enzymatic assembly are applied with
      limited frequency. Methods including atomic force microscopy, fluorescence
      spectroscopy, surface plasmon resonance, and high-pressure procedures all have
      gained popularity in characterization of the proteasome. These methods provide
      significant and often unexpected insight regarding the structure and function of
      the enzyme. This chapter describes the use of atomic force microscopy for dynamic
      structural studies of the proteasome.

PMID- 16275348
TI  - Characterization of noncompetitive regulators of proteasome activity.
AB  - The success of bortezomib, a competitive proteasome inhibitor and a drug approved
      to treat multiple myeloma, spurred interest in compounds targeting catalytic
      sites of the enzyme. The aim of this chapter, however, is to focus attention on
      the small molecule, natural or synthetic compounds binding far away from the
      catalytic centers, yet modifying the performance of the proteasome. Defining
      allostery broadly as any kind of ligand-induced, long-distance transfer of
      conformational signals within a molecule, most such compounds are allosteric
      effectors capable of regulating the proteasome in vitro and in vivo in a manner
      more diverse and precise than competitive inhibitors. Proline- and arginine-rich
      peptides (PR peptides) are examples of such compounds and are currently being
      considered as potential drugs with anti-inflammatory and proangiogenic
      activities. This chapter describes a set of methods useful for characterizing the
      effects of such inhibitors on the proteasome.

PMID- 16275349
TI  - Development and use of antiproteasome monoclonal antibodies.
AB  - This chapter describes the production of hybridomas and screening of monoclonal
      antibodies for use in enzyme-linked immunosorbent assay (ELISA), immunoblotting,
      and immunoprecipitation of components of the ubiquitin-proteasome pathway.
      Purification of antibodies and their use in affinity chromatography are also
      described.

PMID- 16275350
TI  - Preparation and characterization of yeast and human desumoylating enzymes.

PMID- 16275351
TI  - Purification of the COP9 signalosome from porcine spleen, human cell lines, and
      Arabidopsis thaliana plants.
AB  - COP9 signalosome (CSN) is an evolutionarily conserved multisubunit protein
      complex involved in diverse cellular and developmental processes in eukaryotes.
      CSN functions in the cell as proteases that deconjugate Nedd8/Rub1 from cullin
      family proteins and depolymerize ubiquitin chains. As such, CSN represents an
      important regulator of multiple cullin-based E3 ubiquitin ligases. CSN has also
      been shown to associate with protein kinase activities. This chapter describes
      purification of the CSN complex by classical chromatography from porcine spleen
      and by immunoaffinity purification procedures from cultured human cells and
      transgenic Arabidopsis plants expressing epitope-tagged CSN subunits. It also
      describes in vitro deneddylation assays using the HeLa cell extract or the
      Arabidopsis cell extract, which we have used to test and compare the activity of
      purified CSN complexes.

PMID- 16275352
TI  - Purification method of the COP9 signalosome from human erythrocytes.
AB  - The COP9 signalosome (CSN) is a multimeric protein complex that occurs in all
      eukaryotic cells. Originally described in plants as a regulator of
      photomorphogenesis, its purification and characterization from mammalian cells
      revealed significant sequence homologies to subunits of the 26S proteasome lid
      complex, as well as of the eukaryotic translation initiation factor 3. Recent
      studies disclosed its participation in processes such as DNA repair, cell cycle
      regulation, development, and angiogenesis. At the moment, the pleiotropic effects
      of the CSN point to a regulatory role in the ubiquitin/26S proteasome system, but
      its exact function still remains to be clarified. This chapter describes the
      method to purify human CSN from red blood cells. Two outdated erythrocyte
      concentrates are sufficient to prepare approximately 0.5 mg of CSN. Washed cells
      are first lysed and then proteins are separated by a DEAE anion-exchange column.
      The CSN-containing fractions are pooled and subjected to an ammonium sulfate
      precipitation followed by dialysis. The concentrated proteins are then loaded
      onto a glycerol density gradient and ultracentrifugation is performed. The
      purification procedure is continued using two succeeding anion-exchange columns,
      resulting in a sufficiently pure CSN complex. Optionally, an additional density
      gradient centrifugation can be attached. The purified CSN complex possesses
      kinase, deneddylase, and deubiquitinase activities and can be stored for at least
      2 months on ice at 4 degrees .

PMID- 16275354
TI  - Strategies for assaying deubiquitinating enzymes.
AB  - A general method for assaying deubiquitinating enzymes (DUBs) has been developed.
      This new method employs an indirect enzyme assay for determining the activity of
      DUBs using a linear fusion of polyHis-glutathione-S-transferase-ubiquitin-ecotin
      (His-GST-Ub-ecotin) as a substrate. Because ecotin, a trypsin inhibitor protein
      from Escherichia coli, is heat stable, the activity of DUBs can be assayed
      indirectly by determining the ability of ecotin to inhibit trypsin after
      incubation of any DUB with His-GST-Ub-ecotin followed by heating at 100 degrees.
      In the substrate construction, His-GST fusion to Ub was used for facilitation of
      the substrate purification as well as for assisting the heat precipitation of His
      GST-Ub and uncleaved His-GST-Ub-ecotin, as Ub itself is also heat stable. This
      method can also be used for assaying the proteases that process Ub-like proteins
      (Ubls) using the substrates, in which Ub is replaced by Ubls.

PMID- 16275353
TI  - UBP43, an ISG15-specific deconjugating enzyme: expression, purification, and
      enzymatic assays.
AB  - UBP43 is the only deconjugating enzyme for the protein ISGylation system thus far
      identified. UBP43 activity is not critical for precursor processing, as UBP43
      deficent cells can generate ISG15 conjugates upon type I interferon treatment.
      However, UBP43 deficiency caused a defect in the negative regulation of type I
      interferon signaling, resulting in enhanced and prolonged activation of Jak/Stat
      upon type I interferon treatment. This chapter describes the expression,
      purification, and enzymatic assays for UBP43.

PMID- 16275355
TI  - In vitro cleavage of Nedd8 from cullin 1 by COP9 signalosome and deneddylase 1.
AB  - Enzymatic cleavage of Nedd8 from its cullin conjugates plays a critical role in
      ubiquitin-dependent proteolysis by regulating the activity of the cullin-based
      RING-H2 E3 ubiquitin ligases. This chapter provides methods for the preparation
      of two Nedd8 isopeptidases: the COP9 signalosome and human deneddylase 1. It also
      describes the development of cell-free systems for cleavage of the Nedd8-cullin 1
      isopeptide bond formed in vitro or in vivo.

PMID- 16275356
TI  - Ubiquitin-ovomucoid fusion proteins as model substrates for monitoring
      degradation and deubiquitination by proteasomes.
AB  - Protein degradation by 26S proteasomes requires the coordinated action of
      multiple binding and catalytic activities to process ubiquitinated protein
      substrates. For the purpose of studying conjugate degradation independently of
      substrate targeting and unfolding steps, we have developed substrates based on an
      N-terminal fusion of ubiquitin to an irreversibly unfolded protein, the 83 amino
      acid HA epitope-tagged first domain of chicken ovomucoid. Fluorescent labeling of
      the six cysteines in the ovomucoid moiety (OM) with Lucifer Yellow iodoacetamide
      yields UbOM(LY); the ubiquitin in the fusion protein can be extended by the
      addition of a K48-linked polyubiquitin chain to form Ub(n)OM(LY). UbOM(LY)
      derivatives provide versatile substrates to monitor both protein degradation and
      deubiquitination by 26S proteasomes in vitro. Comparisons of polyubiquitin
      conjugates of unfolded OM(LY) with folded dihydrofolate reductase (DHFR) in
      degradation assays can help resolve and identify the rate-limiting steps in
      proteasome degradation.

PMID- 16275357
TI  - Using deubiquitylating enzymes as research tools.
AB  - Ubiquitin is synthesized in eukaryotes as a linear fusion with a normal peptide
      bond either to itself or to one of two ribosomal proteins and, in the latter
      case, enhances the yield of these ribosomal proteins and/or their incorporation
      into the ribosome. Such fusions are cleaved rapidly by a variety of
      deubiquitylating enzymes. Expression of heterologous proteins as linear ubiquitin
      fusions has been found to significantly increase the yield of unstable or poorly
      expressed proteins in either bacterial or eukaryotic hosts. If expressed in
      bacterial cells, the fusion is not cleaved due to the absence of deubiquitylating
      activity and can be purified intact. We have developed an efficient expression
      system, utilizing the ubiquitin fusion technique and a robust deubiquitylating
      enzyme, which allows convenient high yield and easy purification of authentic
      proteins. An affinity purification tag on both the ubiquitin fusion and the
      deubiquitylating enzyme allows their easy purification and the easy removal of
      unwanted components after cleavage, leaving the desired protein as the only
      soluble product. Ubiquitin is also conjugated to epsilon amino groups in lysine
      side chains of target proteins to form a so-called isopeptide linkage. Either a
      single ubiquitin can be conjugated or other lysines within ubiquitin can be
      acceptors for further conjugation, leading to formation of a branched, isopeptide
      linked ubiquitin chain. Removal of these ubiquitin moieties or chains in vitro
      would be a valuable tool in the ubiquitinologists tool kit to simplify downstream
      studies on ubiquitylated targets. The robust deubiquitylating enzyme described
      earlier is also very useful for this task.

PMID- 16275358
TI  - Functional annotation of deubiquitinating enzymes using RNA interference.
AB  - Protein ubiquitination is a dynamic process, depending on a tightly regulated
      balance between the activity of ubiquitin ligases and their antagonists, the
      ubiquitin-specific proteases or deubiquitinating enzymes. The family of ubiquitin
      ligases has been studied intensively and it is well established that their
      deregulation contributes to diverse disease processes, including cancer. Much
      less is known about the function and regulation of the large group of
      deubiquitinating enzymes. This chapter describes how RNA interference against
      deubiquitinating enzymes can be used to elucidate their function. The application
      of this technology will greatly improve the functional annotation of this family
      of proteases.

PMID- 16275360
TI  - Role of regulatory T cells in human diseases.
AB  - The discovery of regulatory T lymphocytes (Treg) that are actively involved in
      maintaining immune tolerance has led to new insights into mechanisms of tolerance
      breakdown in human diseases, including those resulting from allergic, autoimmune,
      or infectious causes. Congenital deficiency of CD4(+)CD25(+) Treg cells caused by
      loss-of-function mutations in the gene encoding Foxp3 triggers a syndrome of
      lymphoproliferation and myeloproliferation, autoimmunity, and allergic
      dysregulation, whereas deficient allergen-specific Treg cell responses have been
      associated with a number of allergic and autoimmune disorders. Tolerization to
      allergens and autoantigens is associated with augmentation of Treg cell numbers
      and suppressive function, suggesting the manipulation of Treg cell activity as a
      potential strategy for future therapeutic interventions in allergic and
      autoimmune diseases.

PMID- 16275361
TI  - T regulatory cells in allergy: novel concepts in the pathogenesis, prevention,
      and treatment of allergic diseases.
AB  - The identification of T regulatory (T(Reg)) cells as key regulators of
      immunologic processes in peripheral tolerance to allergens has opened an
      important era in the prevention and treatment of allergic diseases. Both
      naturally occurring CD4(+)CD25(+) T(Reg) cells and inducible populations of
      allergen-specific IL-10-secreting T(R)1 cells inhibit allergen-specific effector
      cells in experimental models. Allergen-specific T(Reg) cell responses contribute
      to the control of allergic inflammation in several ways. Skewing of allergen
      specific effector T cells to a T(Reg) phenotype appears to be a crucial event in
      the development of a healthy immune response to allergens and successful outcome
      in allergen-specific immunotherapy. The increased levels of IL-10 and TGF-beta
      produced by T(Reg) cells can potently suppress IgE production while
      simultaneously increasing the production of the noninflammatory antibody isotypes
      IgG4 and IgA, respectively. T(Reg) cells directly or indirectly suppress effector
      cells of allergic inflammation, such as mast cells, basophils, and eosinophils,
      and contribute to remodeling in asthma and atopic dermatitis. In addition,
      mediators of allergic inflammation that trigger cyclic AMP-associated G protein
      coupled receptors, such as histamine receptor 2, might play a role in peripheral
      tolerance mechanisms against allergens. Current strategies for drug development
      and allergen-specific immunotherapy exploit these observations with the potential
      to provide cure for allergic diseases.

PMID- 16275362
TI  - Aspirin sensitivity and severity of asthma: evidence for irreversible airway
      obstruction in patients with severe or difficult-to-treat asthma.
AB  - BACKGROUND: Patients with aspirin sensitivity experience hyperplastic sinusitis
      and nasal polyposis. We speculated that similar mechanisms could be acting in the
      lower airway and that these individuals would demonstrate more severe asthma and
      irreversible loss of lung function. OBJECTIVE: We sought to investigate the role
      of aspirin-exacerbated respiratory disease (AERD) as a risk factor for the
      development of irreversible airway obstruction. METHODS: The Epidemiology and
      Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study is a
      multicenter observational study of subjects with severe or difficult-to-treat
      asthma. Data were compared between subjects who reported asthma exacerbation
      after aspirin ingestion and those who did not. The primary measure of
      bronchodilator-resistant obstruction (possible remodeling) was the maximally
      achieved postbronchodilator spirometry averaged over the 3-year duration of the
      study. RESULTS: Adult subjects (>/=18 years) with AERD (n = 459) were compared
      with subjects with non-aspirin-sensitive asthma (n = 2848). Subjects with AERD
      had significantly lower mean postbronchodilator percent predicted FEV(1) compared
      with subjects with non-aspirin-sensitive asthma (75.3% vs 79.9%, P < .001).
      Differences in spirometry between the 2 cohorts persisted after controlling for
      potential confounding variables. In addition, subjects with AERD were more likely
      to have severe asthma by means of physician assessment (66% vs 49%, P < .001), to
      have been intubated (20% vs 11%, P < .001), to have a steroid burst in the
      previous 3 months (56% vs 46%, P < .001), and to have required high-dose inhaled
      corticosteroids (34% vs 26%, P < .001). CONCLUSIONS: These data suggest that
      aspirin sensitivity is associated with increased asthma severity and possible
      remodeling of both the upper and lower airways.

PMID- 16275363
TI  - Spirometric criteria for asthma: adding further evidence to the debate.
AB  - BACKGROUND: Objective assessments of pulmonary function are considered essential
      for the diagnosis of asthma. The degree of reversibility of FEV(1) considered
      supportive of asthma varies between international asthma guidelines. OBJECTIVE:
      We sought to compare the relative performance of international guideline
      reversibility criteria for identifying impairment in persons with a significant
      bronchodilator response (SBR) without an asthma diagnosis. METHODS: The North
      West Adelaide Health (Cohort) Study, a population biomedical study of 4060
      subjects, conducted spirometry according to American Thoracic Society criteria.
      SBR was defined as postbronchodilator FEV(1) responses of at least 12% or 15% of
      baseline values, 9% of predicted values, or 400 mL. A self-completed
      questionnaire assessed current asthma (CA), respiratory symptoms, and participant
      demographics. RESULTS: The prevalence of CA was 9.4% (n = 380), whereas 1.3%
      (>/=400 mL) to 4.5% (>/=9% of predicted value) of participants demonstrated an
      SBR in the absence of CA. With the exception of the 9% predicted criterion,
      prebronchodilator mean FEV(1) (percent predicted) in those demonstrating an SBR
      but no CA was significantly worse than that in the CA group. Significantly more
      respiratory symptoms were experienced by the SBR groups than the group without
      asthma. Logistic regression analyses identified different characteristics of
      those classified by the following criteria: 12% and 15%, age of 40 years or
      greater and household income of less than $40,000; 9% predicted, household income
      of less than $40,000; 400 mL, male sex (odds ratio, 4.5; 95% CI, 2.1-9.3).
      CONCLUSIONS: Different criteria identify different persons, but SBR by any
      criteria was associated with significant respiratory impairment, some of which
      might be attributable to asthma. Postbronchodilator change as a percentage of
      predicted value was the least biased of the criteria.

PMID- 16275364
TI  - Evidence of remodeling in peripheral airways of patients with mild to moderate
      asthma: effect of hydrofluoroalkane-flunisolide.
AB  - BACKGROUND: We have shown previously that inflammation in asthma is not
      restricted to central airways but can also be demonstrated in peripheral airways.
      It is not clear whether inflammation of the peripheral airways is associated with
      structural changes and whether this remodeling process can be modulated by
      deposition of inhaled corticosteroids (ICSs). OBJECTIVES: To compare remodeling
      in peripheral and central airways and to investigate the effects of
      hydrofluoroalkane (HFA)-ICS on remodeling at these sites. METHODS: Transbronchial
      and endobronchial biopsies were obtained from 12 patients with mild to moderate
      asthma before and after a 6-week course of HFA-ICS (flunisolide). Total collagen
      deposition, expression of collagen III, TGF-beta, and alpha-smooth muscle actin
      were examined by using Van Gieson staining and immunocytochemistry, respectively.
      RESULTS: Total collagen occupied 37.7% of the wall area of peripheral airways,
      compared with 54.5% of the wall area of central airways (P = .04). There was no
      significant difference in central versus peripheral airways for collagen III or
      alpha-smooth muscle actin immunoreactivity and in the number of TGF-beta(+) cells
      in the submucosa. The only significant effect of HFA-flunisolide was a decrease
      in alpha-smooth muscle actin area in peripheral airways (13.4% vs 4.6%; P = .01)
      that correlated with the percentage increase in forced expiratory flow at 25% to
      75% of vital capacity (r(s) = -1.00; P = .00). CONCLUSION: Our data show that
      there is a considerable degree of airway remodeling in peripheral airways in
      patients with asthma and confirm the inability of ICS to modulate collagen
      deposition and TGF-beta expression. Treatment with HFA-flunisolide is associated
      with a significant decrease in the expression of alpha-smooth muscle actin in
      peripheral airways, which correlated with improvement in peripheral airway
      function.

PMID- 16275365
TI  - Severity assessment in asthma: An evolving concept.
AB  - BACKGROUND: Guidelines for the clinical management of asthma base specific
      treatment recommendations on the assessment of disease severity. Thus, the
      accuracy of such assessments is essential for proper clinical management. The
      consistency of asthma severity assessment in patients with difficult-to-treat
      disease is unknown. OBJECTIVE: The objectives of this analysis were to compare
      the asthma severity assessment according to 3 methodologies in patients from The
      Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens
      study. METHODS: Asthma severity on the basis of the National Asthma Education and
      Prevention Program and the Global Initiative for Asthma guidelines was compared
      with physician assessment and benchmarked against asthma-related health care use.
      Guideline-based asthma severity symptom components were derived from patient
      reported questionnaires. Lung function levels were determined by
      prebronchodilator FEV(1) measurements; asthma-related medication and recent
      health care use were reported by patients. RESULTS: There was a clear lack of
      agreement among the asthma severity assessment modalities. Asthma severity was
      associated with asthma-related health care use, and patients considered to have
      severe asthma according to both sets of guidelines and physicians' assessment had
      the highest health care and medication use. CONCLUSION: Classification of asthma
      severity on the basis of current asthma symptoms and lung function may be useful
      but not completely reflective of a patient's true asthma condition. Clinical
      assessment of asthma severity should consider a patient's medication use and
      consumption of health care resources for asthma exacerbations. Additional studies
      that apply criteria for asthma severity longitudinally are needed to support
      recommendations for optimal assessment of asthma severity.

PMID- 16275366
TI  - The role of T regulatory cells in asthma.
AB  - As a chronic inflammatory disease, much of the research related to asthma has
      been focused on proinflammatory mechanisms. Recently, advances have been made in
      defining mechanisms that control inflammation and induce immune tolerance to
      specific antigens. Subsets of CD4(+) cells known as T regulatory cells play an
      important role in directing these processes, and recent experiments have begun to
      define crucial molecular and signaling pathways. There is a growing body of
      evidence describing the function of T regulatory cells in the development,
      disease activity, and treatment responses related to asthma and other atopic
      diseases. Collectively, this new information suggests that a greater
      understanding of these pathways might lead to new therapeutic targets for asthma
      and other diseases of chronic airway inflammation.

PMID- 16275367
TI  - Secretory phospholipases A2 in inflammatory and allergic diseases: not just
      enzymes.
AB  - Secretory phospholipases A(2) (sPLA(2)s) are molecules released in plasma and
      biologic fluids of patients with systemic inflammatory, autoimmune, and allergic
      diseases. Several sPLA(2) isoforms are expressed and released by such human
      inflammatory cells as neutrophils, eosinophils, basophils, T cells, monocytes,
      macrophages, and mast cells. Certain sPLA(2)s release arachidonic acid, thereby
      providing the substrate for the biosynthesis of proinflammatory eicosanoids.
      However, there are other mechanisms by which sPLA(2)s might participate in the
      synthesis of lipid mediators. Interestingly, sPLA(2)s activate inflammatory cells
      through mechanisms unrelated to their enzymatic activity. Several sPLA(2)s induce
      degranulation of mast cells and eosinophils and activate exocytosis in
      macrophages. Furthermore, sPLA(2)s promote cytokine and chemokine production from
      macrophages, neutrophils, eosinophils, monocytes, and endothelial cells. Some of
      these effects are mediated by the binding of sPLA(2)s to specific receptors
      expressed on effector cells. Thus sPLA(2)s might play important roles in the
      initiation and amplification of the inflammatory reaction. Selective inhibitors
      of sPLA(2)s and specific antagonists of sPLA(2) receptors might prove useful in
      the treatment of allergic and autoimmune diseases, such as bronchial asthma and
      rheumatoid arthritis.

PMID- 16275368
TI  - Adding salmeterol to an inhaled corticosteroid reduces allergen-induced serum IL
      5 and peripheral blood eosinophils.
AB  - BACKGROUND: Adding a long-acting beta(2)-agonist to inhaled corticosteroids
      results in better symptomatic asthma control than increasing the dose of inhaled
      corticosteroids. OBJECTIVE: Investigating whether adding the long-acting beta(2)
      agonist salmeterol to the inhaled corticosteroid fluticasone propionate has an
      effect on allergen-induced allergic inflammation in asthma. METHODS: Bronchial
      allergen challenges were performed in 26 patients with allergic asthma,
      pretreating them with a single dose of either fluticasone/salmeterol (100/50
      microg) or fluticasone alone (100 microg), in a double-blind, randomized, cross
      over design. Sputum and serum markers of bronchial inflammation were measured
      after allergen challenge, as well as lung function parameters. Primary outcomes
      were sputum eosinophil numbers and eosinophil cationic protein. RESULTS:
      Asthmatic responses after allergen challenge were significantly reduced after
      pretreatment with fluticasone/salmeterol relative to fluticasone alone. Sputum
      inflammatory markers after allergen challenge were not significantly affected by
      fluticasone/salmeterol pretreatment. By contrast, serum IL-5 was significantly
      reduced (geometric mean serum IL-5 [SEM]: 0.5 [0.3] vs 1.1 [0.3] pg/mL 1 hour and
      0.6 [0.3] vs 1.1 [0.3] pg/mL 6 hours after challenge with fluticasone/salmeterol
      vs fluticasone alone pretreatment, respectively; P values < .05). Also,
      peripheral blood eosinophils were significantly reduced (geometric mean number x
      10(6)/L [SEM]: 172 [0.1] vs 237 [0.1] at 6 hours and 271 [0.1] vs 351 [0.1] at 24
      hours with fluticasone/salmeterol vs fluticasone alone pretreatment,
      respectively; P < .05). CONCLUSION: Adding salmeterol to fluticasone reduces
      allergen-induced serum IL-5 and peripheral blood eosinophils. This phenomenon may
      contribute to the improved clinical outcomes that result from adding a long
      acting beta(2)-agonist to inhaled corticosteroids.

PMID- 16275369
TI  - 5-Oxo-6,8,11,14-eicosatetraenoic acid is a potent chemoattractant for human
      basophils.
AB  - BACKGROUND: 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a
      chemoattractant for eosinophils and neutrophils, and the messenger RNA for its
      receptor, the oxo-eicosatetraenoic acid receptor (OXE), has been detected in
      several tissues. OBJECTIVES: This study aimed at clarifying the role of 5-oxo-ETE
      in the regulation of basophil function. METHODS: Basophil responses were
      determined in assays of flow-cytometric shape change, Ca(2+) flux, chemotaxis,
      and histamine release. Messenger RNA for OXE was detected by real-time PCR.
      RESULTS: We observed that human eosinophils were 3 to 10 times more sensitive to
      5-oxo-ETE than neutrophils in flow-cytometric shape change and Ca(2+) flux
      assays, as estimated from the half-maximal responses of the cells. Basophils
      responded to 5-oxo-ETE in the shape change assay with a sensitivity similar to
      that of eosinophils. 5-Oxo-ETE was a weak inducer of Ca(2+) flux in basophils and
      did not cause histamine release but was a highly effective chemoattractant for
      basophils in the low nanomolar concentration range in a pertussis toxin-sensitive
      manner. In agreement with these functional studies, the messenger RNA for the 5
      oxo-ETE receptor, OXE, was detectable in basophils as in monocytes, eosinophils,
      and neutrophils, but not in fibroblasts. Specimens from sinus mucosa, tonsils,
      and adenoids also contained detectable levels of messenger RNA for OXE.
      CONCLUSION: Our data suggest that 5-oxo-ETE is potentially involved in the
      regulation of basophil recruitment and might hence be a useful therapeutic target
      in atopic disease.

PMID- 16275370
TI  - Physiologic assessment of allergic rhinitis in mice: role of the high-affinity
      IgE receptor (FcepsilonRI).
AB  - BACKGROUND: There have been few reports using animal models to study the
      development of allergic rhinitis. Characterization of such a model in mice would
      be advantageous given the availability of reagents and gene-manipulated strains.
      OBJECTIVE: We sought to develop a murine model of allergic rhinitis in the
      absence of lower airway changes. METHODS: After sensitization and challenge, both
      wild-type and FcepsilonRI-deficient mice were studied for their ability to
      develop early- and late-phase nasal responses. In the invasive approach, direct
      measurements of nasal airway resistance (R(NA)) were obtained; in the noninvasive
      approach using whole-body plethysmography, respiratory frequency and expiratory
      and inspiratory times were monitored. In both approaches, nasal responses were
      determined either acutely after challenge (early phase) or 24 hours after
      challenge (late phase). RESULTS: After challenge of sensitized mice, R(NA)
      significantly increased. In parallel, respiratory frequency significantly
      decreased and was highly correlated with the increases in R(NA). Sensitized wild
      type mice had an early-phase nasal response and persistent nasal blockage (late
      phase response) after allergen challenge. In contrast, sensitized and challenged
      FcepsilonRI alpha-chain-deficient mice did not have an early-phase nasal reaction
      and exhibited reduced nasal blockage and lower IL-13 levels in nasal tissue
      homogenates. CONCLUSIONS: These data indicate that FcepsilonRI is essential to
      development of an early-phase nasal response and contributes to the development
      of the late-phase nasal response. These invasive and noninvasive approaches
      provide new opportunities to evaluate the mechanisms underlying the development
      of nasal responses to allergen and to assess various therapeutic interventions.

PMID- 16275372
TI  - Giant ragweed specific immunotherapy is not effective in a proportion of patients
      sensitized to short ragweed: analysis of the allergenic differences between short
      and giant ragweed.
AB  - BACKGROUND: Short ragweed and giant ragweed pollen allergens are considered
      largely cross-reactive, and it is generally believed that 1 species is sufficient
      for skin testing and immunotherapy. However, in the area north of Milan (a zone
      widely invaded only by short ragweed), about 50% of patients submitted to
      injection specific immunotherapy with giant ragweed showed little or no clinical
      response, but showed an excellent outcome if they were shifted to short ragweed
      specific immunotherapy. OBJECTIVE: To investigate allergenic differences between
      short and giant ragweed. METHODS: IgE reactivity to short ragweed of sera from 16
      patients allergic to ragweed was assessed by immunoblot before and after
      absorption with short and giant ragweed. Moreover, 41 ragweed-monosensitive
      patients underwent skin prick test with both ragweed species. RESULTS: In several
      cases, preabsorption of sera with giant ragweed extract was unable to inhibit IgE
      reactivity fully against both a 43-kd allergen and other allergens at different
      molecular weights in short ragweed. On skin prick test, short ragweed induced
      larger wheals than giant ragweed in the majority of patients, and 6 of 41 (15%)
      patients were strongly short ragweed-positive but giant ragweed-negative. The
      immunoblot with the serum from 1 of these subjects showed a strong IgE reactivity
      to short ragweed at about 43 kd in the absence of any reactivity to giant
      ragweed. CONCLUSION: Short and giant ragweed are not allergenically equivalent.
      Allergenic differences involve both the major allergens Amb a 1-2/Amb t 1-2 and
      some minor allergens. In patients allergic to ragweed, both diagnosis in vivo and
      immunotherapy should always be performed by using the ragweed species present in
      that specific geographic area.

PMID- 16275371
TI  - Nitrosative stress in the bronchial mucosa of severe chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Reactive nitrogen species, formed via the reaction of nitric oxide
      (NO) with superoxide anion and via (myelo)peroxidase-dependent oxidation of
      NO(2)(-), have potent proinflammatory and oxidizing actions. Reactive nitrogen
      species formation and nitrosative stress are potentially involved in chronic
      obstructive pulmonary disease (COPD) pathogenesis. OBJECTIVES: To investigate the
      expression of markers of nitrosative stress, including nitrotyrosine (NT),
      inducible NO synthase (iNOS), endothelial NO synthase (eNOS), myeloperoxidase
      (MPO), and xanthine oxidase (XO) in bronchial biopsies and bronchoalveolar lavage
      from patients with mild to severe stable COPD compared with control groups
      (smokers with normal lung function and nonsmokers). METHODS: The expression of
      NT, iNOS, eNOS, MPO and XO in the bronchial mucosa and bronchoalveolar lavage of
      patients was measured by using immunohistochemistry, Western blotting, and ELISA
      and correlated with the inflammatory cell profile. RESULTS: Patients with severe
      COPD in stable phase had higher numbers of NT(+) and MPO(+) cells in their
      bronchial submucosa compared with mild/moderate COPD, smokers with normal lung
      function, and nonsmokers (P < .01). iNOS(+) and eNOS(+) but not XO(+) cells were
      significantly increased in smokers with COPD or normal lung function compared
      with nonsmokers (P < .05 and P < .01, respectively). In patients with COPD, the
      number of MPO(+) cells was significantly correlated with the number of
      neutrophils (r = +0.61; P < .0025) in the bronchial submucosa. Furthermore, the
      number of NT(+) and MPO(+) cells was negatively correlated with
      postbronchodilator FEV(1). CONCLUSION: These data suggest that nitrosative
      stress, mainly mediated by MPO and neutrophilic inflammation, may contribute to
      the pathogenesis of severe COPD.

PMID- 16275373
TI  - Discontinuing nasal steroids might lower intraocular pressure in glaucoma.
AB  - BACKGROUND: Topical, intraocular, oral, and parenteral steroids might increase
      intraocular pressure (IOP), but little is known regarding the effect of nasal
      steroid spray. OBJECTIVE: We sought to examine the effect of discontinuing nasal
      steroid sprays on IOP in patients with glaucoma. METHODS: A retrospective chart
      review of patients with glaucoma using nasal steroids was performed. Averaged IOP
      for each pair of eyes was determined for presteroid use, steroid use, and 2
      consecutive poststeroid use (poststeroid 1 and poststeroid 2) examinations.
      RESULTS: Twenty-four eyes of 12 patients taking nasal steroids were identified.
      The mean IOP for each pair of eyes was 15.4 +/- 4.3 mm Hg (range, 9-23.5 mm Hg)
      for the presteroid use examination, 18.0 +/- 3.8 mm Hg (range, 12-24.5 mm Hg) for
      the steroid use examination, 14.5 +/- 3.3 mm Hg (range, 9.5-20 mm Hg) for
      poststeroid use examination 1, and 14.8 +/- 3.4 mm Hg (range, 95-22.0 mm Hg) for
      poststeroid use examination 2. Eleven patients experienced decreased averaged IOP
      at poststeroid use examination 1 after steroid discontinuation at a mean of 35 +/
      14 days and continued to maintain this decrease on the poststeroid use
      examination 2 visit at a mean of 191 +/- 150 days. A significant increase between
      presteroid and steroid use examination IOPs (P = .007) and a significant decrease
      between steroid use and both poststeroid use 1 (P < .001) and poststeroid use 2
      (P = .011) examination IOPs were observed. No significant difference between
      presteroid use and either poststeroid use examination IOPs (P = 1.00) was found.
      Many patients met their target pressures and were able to avoid or delay
      additional glaucoma therapy. CONCLUSION: A significant reduction in IOP occurred
      with nasal steroid discontinuation in patients with glaucoma. Nasal steroids
      might contribute to IOP increase, and inquiry as to whether a patient has
      glaucoma before medication initiation is warranted.

PMID- 16275374
TI  - Change in IFN-gamma-producing capacity in early life and exposure to
      environmental microbes.
AB  - BACKGROUND: Exposure to environmental microbes in early life might lead to type 1
      skewed T cell responses and therefore reduce the risk of allergic diseases.
      OBJECTIVE: To investigate whether the cytokine responses at birth and at age 3
      months are associated with environmental factors, especially exposure to
      microbes. Living in a farm, level of house dust endotoxin, cleanliness of the
      home, and presence of cats and dogs in the household were studied as possible
      determinants of cytokine production. METHODS: Twelve farmers' and 17 nonfarmers'
      children were studied. Production of IL-4, IL-6, TNF-alpha, and IFN-gamma in cord
      blood and in peripheral blood at 3 months was measured after 8-hour and 24-hour
      stimulation with phorbol ester plus concanavalin A. RESULTS: IFN-gamma responses
      at age 3 months were associated with farming (median, 53 vs 17 pg/mL; P = .019)
      and cats and dogs (49 vs 14 pg/mL; P = .014) (8 hours). Change in IFN-gamma
      producing capacity from birth to 3 months was larger in children with higher than
      median endotoxin concentration in bed dust (P = .038) and in children with a cat
      or dog (P = .005) (8 hours). Increased IL-6 responses at birth were associated
      with cat or dog exposure (P = .004; 8 hours) and endotoxin level in settled dust
      (P = .039; 24 hours). CONCLUSION: The development of IFN-gamma-producing capacity
      during the first 3 months of life is associated with farming, endotoxin in house
      dust, and cat and dog exposure. These environmental characteristics may indicate
      some microbial exposure capable of driving developing immune system toward T(H)1
      responses.

PMID- 16275375
TI  - Importance of the personal endotoxin cloud in school-age children with asthma.
AB  - BACKGROUND: A number of studies have observed associations between the amount of
      endotoxin in urban dust and chronic asthma severity, but a direct relationship
      between personal exposure to household endotoxin and acute asthma worsening has
      not yet been defined. OBJECTIVE: We sought to investigate the relationship
      between day-to-day changes in personal endotoxin exposure and asthma severity.
      METHODS: In the winter and spring of 1999 through 2000, endotoxin exposures were
      monitored in asthmatic schoolchildren by using portable, as opposed to
      stationary, monitors designed to measure inhalable and respirable particulate
      matter less than or equal to 2.5 and 10 microm in diameter. Children were
      followed with daily measurements of FEV(1) and asthma symptoms. RESULTS: Over a
      24-hour period, median daily personal endotoxin exposures ranged from 0.08
      EU/m(3) (measured at a particulate matter size range </=2.5 microm in diameter)
      to 0.37 EU/m(3) (measured at a particulate matter size range </=10 microm in
      diameter). Personal exposures were significantly (P < .001) higher than endotoxin
      measurements from either indoor or outdoor stationary monitors. Moreover,
      individual exposures did not correlate with stationary measurements, suggesting
      that exposures derived from sources in close proximity to the children's personal
      activities might be better correlated with disease severity. Increases in
      personal endotoxin exposures were associated with decreased FEV(1) values and
      increased symptoms. CONCLUSIONS: These findings demonstrate the importance of
      using personal monitoring to both measure and correlate endotoxin exposure with
      asthma severity.

PMID- 16275377
TI  - Two types of eczema--or are there?

PMID- 16275376
TI  - Cost-effectiveness of a home-based environmental intervention for inner-city
      children with asthma.
AB  - BACKGROUND: Exposure to indoor allergens contributes to increased asthma
      morbidity. The Inner-City Asthma Study, a randomized trial involving home
      environmental allergen and irritant remediation among children aged 6 through 11
      years with moderate-to-severe asthma, successfully reduced asthma symptoms. A
      cost-effectiveness analysis can help stakeholders to evaluate the potential costs
      and benefits of adopting such a program. OBJECTIVE: We sought to assess the cost
      effectiveness of the environmental intervention of the Inner-City Asthma Study.
      METHODS: Incremental cost-effectiveness ratios for a 2-year study period were
      calculated. Health outcome was measured as symptom-free days. Resource use
      measures included ambulatory visits, hospitalizations, and pharmaceutical use.
      CIs were obtained by using bootstrapping. RESULTS: The intervention, which cost
      $1469 per family, led to statistically significant reductions in symptom days,
      unscheduled clinic visits, and use of beta-agonist inhalers. Over the year of the
      intervention and a year of follow-up, the intervention cost was $27.57 per
      additional symptom-free day (95% CI, $7.46-$67.42). Subgroup analysis showed that
      targeting the intervention to selected high-risk subgroups did not reduce the
      incremental cost-effectiveness ratio. CONCLUSIONS: A targeted home-based
      environmental intervention improved health and reduced service use in inner-city
      children with moderate-to-severe asthma. The intervention is cost-effective when
      the aim is to reduce asthma symptom days and the associated costs.

PMID- 16275378
TI  - Support for 2 variants of eczema.
AB  - BACKGROUND: Studies investigating the natural history and risk factors for eczema
      have historically considered eczema as a single entity, without regard for the
      individual's atopic status. The association between atopy and eczema is complex,
      and as many as (2/3) of patients with eczema are not atopic. OBJECTIVE: To
      investigate the risk factors for eczema in relation to the child's atopic status
      in a cohort of high-risk children. METHODS: A prospective birth cohort of 263
      children was followed for 5 years and closely examined for eczema. Antenatal and
      postnatal data on environmental exposures were collected by interview. Skin prick
      test to define atopic status was performed at 6 months and 2 and 5 years of age.
      RESULTS: Of the subjects, 66.1% had eczema in the first 5 years, and the majority
      (85.5%) reported onset of rash in the first year. A third of those with eczema
      were not atopic (nonatopic/intrinsic eczema). Children with atopic eczema
      (extrinsic eczema) were more likely to be male, to have been breast-fed longer,
      and to have a history of food allergies, allergic rhinitis, and current wheeze.
      Nonatopic eczema was more common in girls, and an association was found with
      early daycare attendance. CONCLUSION: This study supports the presence of 2
      variants of eczema: atopic eczema occurring early in childhood and nonatopic
      eczema with early daycare attendance. It is likely that environmental factors
      have a different effect on these 2 variants of eczema, and future studies should
      thus consider eczema as 2 variants in determining the effect of attributable
      risks.

PMID- 16275379
TI  - Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind,
      placebo-controlled study with a standardized hazelnut extract.
AB  - BACKGROUND: Food allergy may be life-threatening, and patients affected need to
      receive accurate diagnoses and treatment. Hazelnut has often been implicated as
      responsible for allergic reactions, and trace quantities can induce systemic
      reactions. OBJECTIVE: The aim of this study was to evaluate the efficacy and
      tolerance of sublingual immunotherapy with a standardized hazelnut extract in
      patients allergic to hazelnut. METHODS: This was a randomized, double-blind,
      placebo-controlled study. Inclusion criteria were a history of hazelnut allergy
      and positive skin prick test and double-blind placebo-controlled food challenge
      results. Patients were then randomly assigned into 2 treatment groups (hazelnut
      immunotherapy or placebo). Efficacy was assessed by double-blind, placebo
      controlled food challenge after 8 to 12 weeks of treatment. Blood samples were
      drawn for measurement of specific IgE, IgG(4), and serum cytokines before and
      after treatment. RESULTS: Twenty-three patients were enrolled and divided into 2
      treatment groups. Twenty-two patients reached the planned maximum dose at 4 days.
      Systemic reactions were observed in only 0.2% of the total doses administered.
      Mean hazelnut quantity provoking objective symptoms increased from 2.29 g to
      11.56 g (P = .02; active group) versus 3.49 g to 4.14 g (placebo; NS). Moreover,
      almost 50% of patients who underwent active treatment reached the highest dose
      (20 g), but only 9% in the placebo. Laboratory data showed an increase in IgG(4)
      and IL-10 levels after immunotherapy in only the active group. CONCLUSION: Our
      data confirm significant increases in tolerance to hazelnut after sublingual
      immunotherapy as assessed by double-blind, placebo-controlled food challenge, and
      good tolerance to this treatment.

PMID- 16275380
TI  - In vivo assessment with prick-to-prick testing and double-blind, placebo
      controlled food challenge of allergenicity of apple cultivars.
AB  - BACKGROUND: Apple cultivars have been reported to differ in allergenicity on the
      basis of in vitro and skin prick tests with apple extracts. OBJECTIVES: We sought
      to evaluate the efficacy of the prick-to-prick method in assessing differences in
      allergenicity of apple cultivars and to confirm differences by means of double
      blind, placebo-controlled food challenge (DBPCFC). METHODS: Intra-assay and
      intracultivar variation of prick-to-prick test results were determined in 6 Dutch
      and 8 Spanish patients with apple allergy by using 5 apples of the cultivars
      Golden Delicious, Fuji, and Ecolette in duplicate. In addition, 21 cultivars were
      screened for allergenicity in 15 Dutch patients with birch pollen and apple
      allergy. Two selected cultivars (Golden Delicious and Santana) were tested with
      DBPCFCs. The influence of storage conditions on allergenicity was assessed in 5
      cultivars. RESULTS: Intra-assay variation of skin prick testing was 3.9%, and
      intracultivar variation was 4.1%. A ranking of 21 cultivars was made on the basis
      of prick-to-prick tests in 9 patients. Apple cultivars were classified as of low,
      intermediate, and high allergenicity, with a significant difference between low
      and high allergenicity (P < .001). A significant difference in allergenicity
      determined between Golden Delicious and Santana cultivars (P < .05) was confirmed
      by means of DBPCFC. With 5 cultivars, controlled atmosphere (2.5% oxygen/1%
      carbon dioxide) was shown to reduce allergenicity (P < .001) by 15% compared with
      storage at 2 degrees C. CONCLUSIONS: Prick-to-prick testing with fresh apples is
      a reproducible method of assessing allergenicity. Apples can be classified as of
      low or high allergenicity for the majority of patients. This was confirmed by
      using DBPCFCs. Selection of cultivars and control of storage conditions are both
      viable strategies for reduction of symptoms in patients with apple allergy.

PMID- 16275381
TI  - The natural history of tree nut allergy.
AB  - BACKGROUND: Although 20% of children outgrow peanut allergy, the natural history
      of tree nut (TN) allergy has not been well studied. OBJECTIVE: The goals of the
      study were to estimate the proportion of children who outgrow TN allergy and
      examine predictors of outgrowing it. METHODS: Patients with TN allergy, defined
      as a history of reaction on ingestion and evidence of TN-specific IgE (TN-IgE) or
      positive TN-specific IgE level but no history of ingestion, were evaluated. If
      all current TN-IgE levels were less than 10 kilounits of antibody (kU(A))/L,
      double-blind, placebo-controlled food challenges were offered. Patients who had
      undergone open TN challenges as part of routine clinical care were also included.
      RESULTS: Two hundred seventy-eight patients with TN allergy were identified. One
      hundred one (36%) had a history of acute reactions, 12 (12%) of whom had
      reactions to multiple TNs and 73 (63%) of whom had a history of moderate-to
      severe reactions. Nine of 20 patients who had previously reacted to a TN passed
      challenges, so that 9 (8.9%; 95% CI, 4% to 16%) of 101 patients with a history of
      prior TN reactions outgrew TN allergy. Fourteen of 19 who had never ingested TNs
      but had detectable TN-specific IgE levels passed challenges. One hundred sixty
      one did not meet the challenge criteria, and 78 met the criteria but declined
      challenges. Looking at specific TN-IgE cutoffs, 58% with TN-IgE levels of 5
      kU(A)/L or less and 63% with TN-IgE levels of 2 kU(A)/L or less passed
      challenges. CONCLUSIONS: Approximately 9% of patients outgrow TN allergy,
      including some who had prior severe reactions. Although ideal cutoffs for
      challenge cannot be firmly recommended on the basis of these data, patients aged
      4 years or older with all TN-IgE levels of 5 kU(A)/L or less should be considered
      for challenge.

PMID- 16275382
TI  - Factors that regulate naturally occurring T regulatory cell-mediated suppression.
AB  - T regulatory (Treg) cells play a key role in the modulation of allergic and
      autoimmune responses. This review will discuss the factors that regulate
      naturally occurring Treg (nTreg) cell-mediated suppression. The involvement of
      cytokines, costimulatory molecules, and ligands on antigen-presenting cells in
      the inhibition of nTreg cell-mediated suppression in vitro is summarized.
      Understanding the events that control suppressive function of nTreg cells will
      allow manipulation of these cells to inhibit or enhance their functions in the
      development of novel therapies for autoimmune and allergic diseases.

PMID- 16275383
TI  - Sporadic case of warts, hypogammaglobulinemia, immunodeficiency, and
      myelokathexis syndrome.
AB  - The term WHIM syndrome (WHIMS) is an acronym describing a rare primary
      immunodeficiency disorder characterized by warts, hypogammaglobulinemia,
      immunodeficiency, and myelokathexis, the unusual association of neutropenia with
      bone marrow myeloid hypercellularity. WHIMS was recently associated with
      mutations in the gene encoding the chemokine receptor CXCR4 and as such is the
      first disease ascribed to abnormalities of chemokine signaling. We report a
      sporadic case of WHIMS in a woman presenting with recurrent infections and human
      papilloma virus-related genital dysplasia.

PMID- 16275384
TI  - Allergic dysregulation and hyperimmunoglobulinemia E in Foxp3 mutant mice.
AB  - BACKGROUND: Regulatory T cells have been proposed to play an important role in
      regulating allergic inflammation. The transcription factor Foxp3 is a master
      switch gene that controls the development and function of natural and adaptive
      CD4(+)CD25(+) regulatory T (T(R)) cells. In human subjects loss-of-function Foxp3
      mutations trigger lymphoproliferation, autoimmunity, and intense allergic
      inflammation in a disease termed immune dysregulation polyendocrinopathy
      enteropathy-X-linked syndrome. OBJECTIVE: We sought to examine the evolution and
      attributes of allergic inflammation in mice with a targeted loss-of-function
      mutation in the murine Foxp3 gene that recapitulates a known disease-causing
      human Foxp3 mutation. METHODS: Foxp3 mutant mice were generated by means of knock
      in mutagenesis and were analyzed for histologic, immunologic, and hematologic
      abnormalities. The role of signal transducer and activator of transcription 6
      (Stat6) in disease pathogenesis was analyzed by using Stat6 and Foxp3 double
      mutant mice. RESULTS: Foxp3 mutant mice developed an intense multiorgan
      inflammatory response associated with allergic airway inflammation, a striking
      hyperimmunoglobulinemia E, eosinophilia, and dysregulated T(H)1 and T(H)2
      cytokine production in the absence of overt T(H)2 skewing. Concurrent Stat6
      deficiency reversed the hyperimmunoglobulinemia E and eosinophilia and delayed
      mortality, which is consistent with a pathogenic role for allergic inflammation
      in Foxp3 deficiency. CONCLUSION: Allergic dysregulation is a common and
      fundamental consequence of loss of CD4(+)CD25(+) T(R) cells caused by Foxp3
      deficiency in different species. Abnormalities affecting T(R) cells might
      contribute to a variety of allergic diseases.

PMID- 16275385
TI  - Combination of corticosteroid therapy and allergen avoidance reverses allergen
      induced airway remodeling in mice.
AB  - BACKGROUND: Allergen avoidance and anti-inflammatory therapy are standard
      therapeutic approaches guidelines advocate to control asthma symptoms. Currently,
      it is not known whether such strategies reduce airway remodeling. OBJECTIVE: We
      have therefore used a mouse model of allergen-induced airway remodeling to
      determine whether allergen avoidance combined with corticosteroid therapy can
      reverse established airway remodeling. METHODS: Mice were sensitized to ovalbumin
      and then repetitively challenged with intranasal ovalbumin for 3 months to
      develop structural features of airway remodeling including peribronchial fibrosis
      and increased thickness of the peribronchial smooth muscle layer. At this time
      point, mice were treated with allergen avoidance, allergen avoidance and
      corticosteroids, or corticosteroids for 1 month to determine whether either
      strategy could reverse established airway remodeling. RESULTS: Mice repetitively
      challenged with ovalbumin developed peribronchial fibrosis (increased total lung
      collagen and increased peribronchial trichrome staining) as well as increased
      thickness of the peribronchial smooth muscle layer. Allergen avoidance
      significantly reduced airway inflammation and mucus expression, slightly reduced
      peribronchial fibrosis, and had no effect on the thickness of the peribronchial
      smooth muscle layer. Addition of corticosteroids to allergen avoidance
      significantly reduced levels of peribronchial fibrosis as well as the thickness
      of the peribronchial smooth muscle layer. CONCLUSION: Allergen avoidance reduces
      airway inflammation and mucus expression but has more limited immediate effects
      on reducing structural features of established airway remodeling. The combination
      of allergen avoidance and corticosteroid therapy is effective in reversing
      established features of airway remodeling including peribronchial fibrosis and
      the increased thickness of the smooth muscle layer.

PMID- 16275386
TI  - Chlamydophila (Chlamydia) pneumoniae serology and asthma in adults: a
      longitudinal analysis.
AB  - BACKGROUND: Many cross-sectional studies have found an association between
      Chlamydophila pneumoniae infection and asthma, and a possible causative role of C
      pneumoniae infection in asthma pathogenesis has been proposed. No longitudinal
      studies have been undertaken to estimate the effect on asthma incidence of
      previous or chronic infection. OBJECTIVE: We evaluated whether serological
      findings suggestive for recent or chronic C pneumoniae infection affect asthma
      risk or lung function during follow-up. METHODS: We followed a population-based
      adult cohort for 15 years and made a clinical evaluation of persons with new
      persistent asthma (n = 83) and matched controls (n = 162). Serological testing
      was performed by microimmunofluorescence and enzyme immunoassay from both
      baseline and follow-up samples. RESULTS: Subjects with serologically diagnosed
      recent or chronic C pneumoniae infection did not run a higher risk of new asthma.
      An increased risk was found in subjects with allergic rhinitis, low lung
      function, history of smoking, and positive family background of asthma or
      allergy. However, chronic C pneumoniae infection was found to accelerate the loss
      of lung function significantly in subjects who contracted new nonatopic asthma
      (median change in FEV(1), 89.6 vs 55.9 mL/y; P = .032). CONCLUSION: Chronic C
      pneumoniae infection promotes the development of airflow limitation in adults
      with nonatopic asthma. However, our results indicate that at the population
      level, any possible effect of C pneumoniae infection on asthma incidence is of
      minor significance.

PMID- 16275387
TI  - Role of mast cells in otitis media.
AB  - BACKGROUND: New pathophysiologic concepts are needed to explain the clinically
      observed connection between the allergic diathesis and otitis media. Although
      mast cells, unlike lymphocytes, are common in the normal middle ear mucosa, their
      potential role in innate immunity of the middle ear and in the expression of
      inflammatory responses in that space to bacterial challenge, as opposed to
      allergy, has received relatively little attention. OBJECTIVE: In the current
      study, we examine the contributions of mast cells to the pathogenesis of
      bacterially induced inflammation in the middle ear and thus to otitis media.
      METHODS: Wild-type mice, mast cell-deficient mice, and mast cell-deficient mice
      whose mast cell populations were restored by transplantation of bone marrow
      derived mast cells were challenged by using models of bacterial and allergic
      middle ear inflammation. RESULTS: Our results indicate that mast cells account
      for a substantial proportion of the innate immune response to bacteria in the
      middle ear. CONCLUSION: This mechanism may link responses to allergy and
      infection in the middle ear mucosa, and thus the mast cell may be a critical
      control element in the pathogenesis of otitis media.

PMID- 16275388
TI  - Functional plasticity of human respiratory tract dendritic cells: GM-CSF enhances
      T(H)2 development.
AB  - BACKGROUND: Dendritic cells within the human respiratory mucosa (RTDCs) are
      proposed to initiate immune responses to foreign antigens. Their capacity to
      polarize T-cell responses, however, has not been investigated. OBJECTIVE: To
      compare RTDCs with peripheral blood dendritic cells (PBDCs) with regard to
      phenotype, cytokine production, capacity to polarize T-cell responses, and
      effects of exposure to the pleiotropic cytokine, GM-CSF. METHODS: CD1a(+) RTDCs
      and CD1c(+) PBDCs were purified from nasal turbinates of patients with nonatopic
      rhinitis and peripheral blood of healthy individuals, respectively. In some
      experiments, matched CD1c(+) RTDCs and PBDCs from patients with rhinitis were
      compared. The phenotype of DC was examined by flow cytometry and cytokine
      production by cytometric bead array. DCs were cocultured with allogeneic naive
      CD4(+) T cells, and cytokine production was determined by immunophenotyping,
      cytometric bead array, and ELISA. RESULTS: Both RTDCs and PBDCs exhibited an
      immature phenotype, but RTDCs expressed lower levels of MHC class II antigen.
      Cross-linking of CD40 on PBDCs, but not RTDCs, induced production of IL-12p70. In
      mixed lymphocyte cultures, RTDCs induced a T(H)1/T(H)2 profile, whereas PBDCs
      induced a T(H)1 profile. Exposure of RTDCs to GM-CSF induced a T(H)2 pattern of
      response in the mixed lymphocyte cultures. In contrast, exposure of PBDCs to GM
      CSF promoted a T(H)1 response. CONCLUSION: This report emphasizes the importance
      of studying tissue-derived primary DCs, demonstrates functional plasticity of
      RTDCs, and implicates GM-CSF in amplifying the potential of RTDCs to initiate
      T(H)2 responses in the airways.

PMID- 16275390
TI  - Control of IgE and selective T(H)1 and T(H)2 cytokines by PG102 isolated from
      Actinidia arguta.
AB  - BACKGROUND: Various allergic responses are thought to result from the unbalanced
      development of T(H)1 and T(H)2 pathways and, subsequently, the overproduction of
      IgE. Therefore the modulation of T(H)1 and T(H)2 responses is a rational strategy
      for the treatment of allergic diseases. OBJECTIVE: The present study was
      performed to investigate the immune-modulating activities of PG102 preparations
      from Actinidia arguta in ovalbumin-sensitized murine models. METHODS: Two
      preparations from A arguta, PG102T and PG102E, were chosen for animal
      experimentation on the basis of their ability to regulate the production of IgE
      in U266B1 cells. The changes in splenic levels of cytokines and plasma levels of
      immunoglobulin isotypes were examined. The effects of PG102 on subcellular
      composition (CD4(+)IL-4(+) or CD19(+)IgE(+) cells), IgE production in B cells,
      and selective transcription factors were analyzed. RESULTS: Oral administration
      of PG102T and PG102E significantly decreased the level of selective T(H)2
      cytokines, whereas it increased the level of T(H)1 cytokines. The differential
      effects of PG102T and PG102E on T(H)1 and T(H)2 cytokines were accompanied by a
      decrease in the plasma levels of IgE and IgG1 and by an increase in the plasma
      level of IgG2a. The percentages of both IL-4-producing T cells and IgE-producing
      B cells were decreased. The concentration of IgE produced within B cells also
      appeared to be reduced. Finally, PG102T and PG102E downregulated the level of
      GATA-binding protein 3, while inducing that of T-box transcription factor and
      nuclear factor of activated T cells c2. CONCLUSION: PG102T and PG102E have great
      potential as orally active immune modulators for the therapy of various allergic
      diseases.

PMID- 16275389
TI  - IL-17 suppresses TNF-alpha-induced CCL27 production through induction of COX-2 in
      human keratinocytes.
AB  - BACKGROUND: The chemokine CCL27 attracts skin-homing T cells. CCL27 production by
      keratinocytes is dependent on nuclear factor kappaB (NF-kappaB) activity and
      enhanced in lesions of patients with atopic dermatitis, psoriasis vulgaris, or
      allergic contact dermatitis. IL-17 is released from activated memory T cells and
      modulates skin inflammation. OBJECTIVE: We examined the in vitro effects of IL-17
      on TNF-alpha-induced CCL27 production in human keratinocytes. METHODS:
      Keratinocytes were incubated with TNF-alpha, IL-17, or both. CCL27 secretion and
      mRNA levels were analyzed by means of ELISA and RT-PCR, respectively. COX-2
      promoter and NF-kappaB activities were analyzed by using luciferase assays. COX-2
      protein levels were analyzed by means of Western blotting. RESULTS: IL-17
      suppressed TNF-alpha-induced CCL27 secretion and mRNA expression and NF-kappaB
      activity in keratinocytes. The COX-2 inhibitor NS398 counteracted the effects of
      IL-17, and prostaglandin E(2) prevented counteraction by NS398. IL-17 alone or
      synergistically with TNF-alpha increased prostaglandin E(2) release from
      keratinocytes, and the increase was suppressed by NS398. IL-17 alone or
      synergistically with TNF-alpha increased COX-2 mRNA and protein levels, promoter
      activity, and mRNA stability. The stimulatory effects of IL-17 on COX-2
      expression were suppressed by inhibitors of p38 mitogen-activated protein kinase
      (MAPK) and extracellular signal-regulated kinase (ERK) kinase. IL-17 alone or
      synergistically with TNF-alpha induced dual phosphorylation of p38 MAPK and ERK.
      CONCLUSION: IL-17 might suppress TNF-alpha-induced CCL27 production by inhibiting
      NF-kappaB through induction of COX-2. The induction of COX-2 might be mediated by
      activation of p38 MAPK and ERK. T cell-derived IL-17 might alleviate T-cell skin
      infiltration through inhibition of CCL27 production.

PMID- 16275391
TI  - CD4+CD25+ T-regulatory cells are decreased in patients with autoimmune
      polyendocrinopathy candidiasis ectodermal dystrophy.

PMID- 16275392
TI  - False-elevated serum tryptase assay result caused by heterophilic antibodies.

PMID- 16275393
TI  - Caseating granulomatous disease in common variable immunodeficiency treated with
      infliximab.

PMID- 16275394
TI  - Relationship between exhaled nitric oxide and body mass index in children and
      adolescents.

PMID- 16275396
TI  - Type 2 natural killer cells in asthma?

PMID- 16275398
TI  - Major and minor determinants are high-performance skin tests in beta-lactam
      allergy diagnosis.

PMID- 16275400
TI  - Carbapenem cross-reactivity with penicillin.

PMID- 16275403
TI  - Large vestibular aqueduct syndrome: audiological, radiological, clinical, and
      genetic features.
AB  - PURPOSE: The aim of this study was to analyze the clinical, audiological,
      radiological, and genetic features of a group of patients affected with large
      vestibular aqueduct syndrome. MATERIALS AND METHODS: Seventeen patients affected
      with large vestibular aqueduct syndrome (LVAS), diagnosed by means of high
      resolution magnetic resonance imaging of the inner ear, with 3-dimensional
      reconstructions of the labyrinth and by high-resolution spiral computed
      tomography of the temporal bone, performed only on the oldest patients, have been
      submitted to a complete audiological evaluation, a thyroid functional and
      ultrasonographic study, and a molecular study of the PDS gene. RESULTS: The
      clinical presentation of LVAS was very variable in our group of patients. The
      enlarged vestibular aqueduct was bilateral in 15 cases and unilateral in 2; it
      was the only malformation of the labyrinth in 12 patients, whereas it was
      associated with other inner ear anomalies in the other 5. The hearing loss was
      very variable in degree (from mild to profound), age at onset, and progression.
      Moreover, among the 17 patients, 10 were clinically affected by Pendred's
      syndrome (PS), 3 by distal renal tubular acidosis associated with large
      vestibular aqueduct, whereas in 3 patients the large vestibular aqueduct was not
      syndromal. Finally, we identified mutations in the PDS gene in 5 of 10 patients
      with PS. CONCLUSIONS: Our data underscore the frequent role of the large
      vestibular aqueduct syndrome in the pathogenesis of sensorineural hearing loss
      and the overall wide variability in its audiological features. It is also
      highlighted that LVAS is often part of some syndromal diseases, most of which are
      PS, which is often misdiagnosed because of the varying degree of thyroid
      symptoms. This study also underscores the possible role of hydro-electrolyte and
      acid-base endolymphatic fluid disorders in the pathogenesis of enlarged
      vestibular aqueduct syndrome.

PMID- 16275404
TI  - Locations of congenital cholesteatoma in the middle ear in Japanese patients.
AB  - OBJECTIVES: To present clinical features of congenital cholesteatoma treated in
      our institute and to investigate the locations of congenital cholesteatoma in the
      middle ear of Japanese patients to verify its pathogeneses. PATIENTS AND METHODS:
      A retrospective chart review of patients in our institute and a review of
      articles on congenital cholesteatoma reported by Japanese researchers. Charts of
      the 25 patients with congenital cholesteatoma treated in our institute were
      reviewed regarding symptoms, locations of cholesteatoma in the middle ear, and
      ossicular anomalies. The same points were investigated in the 71 cases in the
      Japanese literature. RESULTS: Unlike Westerners, more than half of the Japanese
      cases had posterior-type cholesteatomas, any parts of which did not exist
      anteriorly beyond the handle of the malleus. Congenital ossicular anomalies,
      absence of the long process of the incus, and/or the superior structure of the
      stapes were seen with a high rate in the Japanese patients. CONCLUSIONS: These
      two findings of the posterior location of cholesteatomas in the middle ear and
      the high incidence of congenital ossicular anomalies in the Japanese patients
      suggested that there should be some racial difference in pathogenesis of
      congenital cholesteatoma. The pathogenesis of congenital cholesteatoma cannot be
      adequately explained by only one theory alone. It is more appropriate to explain
      the pathogenesis by using an aggregation of theories.

PMID- 16275405
TI  - Discoordination of laryngeal and respiratory movements in aged rats.
AB  - Voice and swallowing actions require the coordination of multiple motor systems,
      and this coordination may be impaired with aging. Although recent work has
      reported impairments in age-related laryngeal kinematics in rats, the temporal
      relationship of laryngeal excursions to the respiratory cycle is unknown. The
      goal of this study was to assess laryngeal-respiratory coordination by examining
      temporal interrelationships between change in laryngeal aperture and chest wall
      movement during quiet breathing in a rat model. Glottal images were recorded,
      digitized, and synchronized with respiratory signals, and temporal features were
      measured. In the young animals, glottal opening began before the onset of
      inspiration, and glottal and respiratory cycles were phasic and stereotypic. In
      old animals, however, inspiration often began during the glottal closing phase,
      and both respiratory signals were asymmetric. Discoordination of laryngeal and
      respiratory motor actions associated with aging may be caused by a generalized
      decline in sensorimotor cranial functions and may contribute to age-related
      swallowing and communication impairment.

PMID- 16275406
TI  - Methylenetetrahydrofolate reductase gene mutations as risk factors for sudden
      hearing loss.
AB  - Sudden hearing loss (SHL) can be caused by vascular disorders favoring impaired
      cochlear perfusion. Several inherited prothrombotic risk factors have been
      considered in the pathogenesis of vascular impairment, and the possible role of
      genetic alterations has recently been suggested. Methylenetetrahydrofolate
      reductase (MTHFR) gene mutations at nucleotides 677 and 1298 cause reduced MTHFR
      enzyme activity, which leads to increased homocysteine and reduced serum folate
      levels that are known to be involved in vascular impairment. We studied the
      relationship between SHL and MTHFR C677T and A1298C gene polymorphisms in 67
      patients with SHL and 134 controls. Wild-type MTHFR CC677/AA1298 was
      significantly more frequent in the controls (P = .05), and gene mutations were
      significantly more frequent in the patients (P = .001; P = .001 for trend). Fifty
      three patients (79.1%) and 56 controls (41.8%) (P = .012) had a double mutation
      (homozygosis 677TT or 1298CC; compound heterozygosis for both polymorphisms).
      Homocysteine levels were significantly higher and serum folate levels
      significantly lower in the patients than in the controls (P < .0001). These data
      suggest that MTHFR gene polymorphisms may be involved in the pathogenesis of SHL.

PMID- 16275407
TI  - Elective neck dissection during salvage laryngectomy.
AB  - PURPOSE: To evaluate the rate of occult metastases detected with elective neck
      dissection during salvage laryngectomy for radiation failures. METHODS AND
      MATERIALS: Retrospective review of 63 patients failing radiation therapy treated
      with salvage surgery between 1970 and 1999. Charts were reviewed for tumor stage,
      neck treatment, complications, surgical time, and survival. Median follow-up for
      patients with glottic and supraglottic cancers was 7.8 and 4.5 years,
      respectively. RESULTS: Thirty-one of 41 glottic cancer patients received elective
      neck dissections. Three (10%) of 31 had occult metastases. Recurrent staged rT3
      and greater tumors showed a 20% rate of occult metastases. No survival advantage
      was noted between patients treated with elective neck dissection and those
      followed expectantly (P = .87). Cartilage invasion and perineural invasion in the
      larynx were associated with a higher risk of occult metastases (P < .05). Ten of
      22 supraglottic cancer patients received elective neck dissections. Two (20%) of
      10 had occult metastases, and a statistically significant survival advantage was
      not noted (P = .49). CONCLUSIONS: We recommend bilateral neck dissection at the
      time of laryngectomy for recurrent staged rT3/4 tumors and all patients with
      recurrent supraglottic cancers because of the higher rate of occult metastases.

PMID- 16275409
TI  - Airway compromise caused by hematoma after thyroid fine-needle aspiration.
AB  - Thyroid fine needle aspiration is a very common procedure used to assess thyroid
      nodules; complications from this procedure are rare. We report an unusual case of
      a large hematoma of the neck caused by thyroid fine needle aspiration that caused
      airway compromise. The hematoma was successfully drained via a transcervical
      approach. In this case report, we also review the literature for the complication
      rate of this ubiquitous procedure.

PMID- 16275408
TI  - Tympanic membrane changes in central tympanic membrane perforations.
AB  - PURPOSE: The objective of this study was to evaluate the histopathological
      changes in central tympanic membrane perforations caused by chronic otitis media
      without cholesteatoma. MATERIALS AND METHODS: Twenty-nine temporal bones from 25
      patients (13 male patients and 12 female patients) with central tympanic membrane
      perforations-18 chronic otitis media with perforation and 11 chronic otitis media
      with perforation caused by ventilation tubes-and 30 aged-matched normal temporal
      bones were included in this study. A scale was used to evaluate the extension of
      the migration of stratified squamous epithelium in the inner surface of the
      tympanic membrane. The thickness of tympanic membranes was measured halfway
      between the annular ligament and the perforation and compared with that of the
      normal bones. The presence of tympanosclerosis and papillary projections of
      squamous epithelium was also noted. RESULTS: The extension of the migration of
      stratified squamous epithelium in the inner surface of the tympanic membrane was
      observed in 11 of the 29 perforations (38%). The thickness of tympanic membranes
      was significantly different between the perforation groups and the control group.
      Of the 29 tympanic membranes, 13 (44%) had tympanosclerosis and 8 (28%) revealed
      papillary projections of squamous epithelium. CONCLUSIONS: Our study shows that a
      central tympanic perforation should not merely be considered as a simple defect.
      Most of the tympanic membranes showed one or more signs of sequelae or persistent
      abnormalities such as tympanosclerosis, papillary projections, thickening, and
      ingrowth without significant differences between the 2 central perforation
      groups.

PMID- 16275410
TI  - T1N0 laryngeal sarcomatoid carcinoma that showed rapid systemic metastases after
      radical radiotherapy: a case report and review of literature.
AB  - Sarcomatoid carcinomas of the larynx account for less than 1% of all malignant
      laryngeal tumors and there is currently no consensus regarding the clinical
      course or appropriate management of this disease. A case of sarcomatoid carcinoma
      of the larynx displaying rapid systemic progression after radiotherapy and a
      brief review of the literature are presented.

PMID- 16275411
TI  - Adult nasal dermoid sinus cyst.
AB  - Nasal dermoid sinus cysts (NDSCs) are uncommon occurrences that require
      intervention usually because of complications with cyst expansion such as
      chemical meningitis, infection, and sequelae of mass effect such as new-onset
      seizures. Although many cysts are removed in childhood, some are not detected
      until adulthood. They become symptomatic and further evaluations illuminate an
      NDSC that has progressed. Most present as extracranial lesions in childhood and
      are effectively removed via open rhinoplasty with no recurrence; however,
      occasionally, they extend intracranially. This case report presents a unique
      (unusual) extension of the NDSC into the frontal sinus requiring an osteoplastic
      flap to access the frontal sinus floor combined with a local midline nasal
      incision at the sinus tract origin. A discussion of various clinical
      presentations and surgical approaches and a case report of a 35-year-old man are
      presented. This case adds to the growing amount of literature on NDSCs and
      demonstrates an unusual presentation, which has thus far not been documented.

PMID- 16275412
TI  - Peripheral facial nerve paralysis after peritonsillar infiltration of
      bupivacaine: a case report.
AB  - Peritonsillar infiltration of a local anesthetic solution for reduction of
      posttonsillectomy pain is commonly used although the benefit and complications of
      this technique have not yet been well established. We report a case of a 4-year
      old boy who developed peripheral facial nerve paralysis after perioperative
      infiltration of bupivacaine and uneventful tonsillectomy. The paralysis was
      noticed a few minutes after extubation and resolved completely after 8 hours. We
      assumed this to be caused by the direct action of the local anesthetic agent on
      the facial nerve.

PMID- 16275413
TI  - Intraparotid Kikuchi-Fujimoto disease masquerading as a parotid gland tumor.
AB  - The Kikuchi-Fujimoto disease, also known as histiocytic necrotizing
      lymphadenitis, is a self-limiting lesion of unknown cause first described in 1972
      independently by Kikuchi and Fujimoto et al. This self-limiting disorder usually
      occurs in Asian women in their late 20s or early 30s. Typically, it runs a benign
      course and appears to resolve spontaneously 1 to 6 months after definite
      diagnosis. The Kikuchi-Fujimoto disease usually manifests as a localized cervical
      lymphadenopathy; therefore, most patients with this disease are seen in ears,
      nose, and throat practice. Nodal involvement other than in the neck area or
      extranodal involvement is rare. In this situation, however, the Kikuchi-Fujimoto
      disease is easily confused with other less-benign conditions. We describe a case
      of Kikuchi-Fujimoto disease in a 30-year-old man that presented as a parotid
      gland tumor. This is the third study to document intraparotid Kikuchi-Fujimoto
      disease in the English literature. Our report illustrates the clinical features
      of this unusual condition and emphasizes potential confusion with other
      diagnoses.

PMID- 16275415
TI  - Undifferentiated carcinoma arising from the Stensen's duct: a case report and
      review of the literature.
AB  - Primary carcinoma arising in Stensen's duct is an extremely rare and poorly
      understood tumor. A 38-year-old man was referred with a malignant lesion situated
      in the right cheek. The patient was treated by local resection, total
      parotidectomy, and modified radical neck dissection. Microscopic examination
      revealed tumor cells of basaloid pattern with squamous differentiation in some
      areas. The tumor showed a very aggressive behaviour with early local recurrence
      and metastatic disease. The histological and radiological findings suggest the
      origin from the Stensen's duct. Primary carcinoma of Stensen's duct should be
      histologically consistent with epidermoid, mucoepidermoid, or undifferentiated
      carcinoma. The diagnosis of true Stensen's duct carcinoma can be performed on the
      basis of clinical presentation, radiological findings, and tumor histology.
      Criteria for determination of origin in the duct are revised and compared with
      this case.

PMID- 16275414
TI  - The magnetic resonance imaging profile of occult intracranial violations as a
      result of sinus surgery.
AB  - INTRODUCTION: Intracranial injury is a well-described complication of sinus
      surgery. Although such complications are typically associated with catastrophic
      morbidity, the neurological sequelae may be subtle and even unrecognized during
      the postoperative period. Magnetic resonance imaging (MRI), which can distinguish
      intracranial hemorrhage and injury, may provide a means for the accurate
      assessment of atypical presentations of occult intracranial complications.
      OBJECTIVE: To describe the MRI profile of occult intracranial complications that
      result from unrecognized skull base violation during sinus surgery. METHOD:
      Retrospective chart review. RESULTS: Two patients, who had endoscopic sinus
      surgery performed elsewhere, underwent postoperative MR for further evaluation of
      headache. The available medical records, as well as the patient's personal
      reports, suggested that no intraoperative cranial base compromise had occurred.
      Both MRIs showed abnormal signal intensity in the brain parenchyma adjacent to
      the floor of the anterior cranial fossa; these findings are consistent with
      traumatic injury presumably from the surgical procedure. Neither patient
      developed postoperative cerebrospinal fluid rhinorrhea, and neither patient
      experienced focal neurological deficits. CONCLUSION: New-onset and/or atypical
      headache after sinus surgery may be associated with occult intracranial injury.
      MRI may serve as the diagnostic means for this occult intracranial violation.
      Significant incongruity may exist between patient symptoms and the objective MR
      evidence that can suggest serious intracranial injury. MRI signal patterns can
      provide both temporal and anatomical cues about the specific injury.

PMID- 16275416
TI  - Frontal sinus hamartomas.
AB  - OBJECTIVE: To review the entity of respiratory epithelial adenomatoid hamartoma
      of the paranasal sinuses using an illustrative case example of frontal sinus
      hamartoma. METHODS: Case report with review of the literature. RESULTS:
      Respiratory epithelial adenomatoid hamartoma represents a benign process that is
      generally cured with conservative surgical resection of the involved area.
      Nevertheless, as shown in our case example, this can be a locally aggressive
      process that can lead to significant morbidity if left untreated. CONCLUSION:
      Hamartomas of the paranasal sinuses represent a rare entity, which should be
      considered in the differential diagnosis of expansile sinonasal lesions.
      Treatment of choice is surgical resection. Frontal sinus involvement may extend
      into the surrounding orbit and intracranial cavities, which may need to be
      addressed with standard skull base surgery techniques.

PMID- 16275417
TI  - Tracheomalacia secondary to obstructive sleep apnea.
AB  - Tracheomalacia (TM) is abnormal flaccidity of the trachea caused by inadequate
      cartilaginous support by the C-shaped tracheal rings. This defect generally
      results in various degrees of dynamic narrowing of the airway lumen. TM usually
      presents with expiratory stridor, wheeze, and respiratory obstruction. TM is
      usually associated with tracheoesophageal fistula and esophageal atresia or with
      other thoracic lesions of vascular rings and tumors. We report a well-documented
      case of a 20-month-old boy who presented to our institution with a severe history
      of obstructive sleep apnea and adenotonsillar hypertrophy. On direct
      laryngoscopy/bronchoscopy, severe TM was noted. Tonsillectomy and adenoidectomy
      was performed, and by the 37th postoperative day, the TM had completely resolved.
      We review the literature, discuss the differential diagnosis and clinical
      evaluation, and propose a new pathophysiological mechanism by which obstructive
      sleep apnea causes TM.

PMID- 16275418
TI  - Aspergillosis: a nidus of maxillary antrolith.
AB  - We present a case of polypoid sinusitis with maxillary sinus antrolith, which is
      composed of Aspergillus species. Unlike most muddy or necrotic fungal balls, this
      first reported fungal antrolith is solid and extremely hard. Aspergillus served
      as a central fungal nidus associated with long-standing sinusitis, and poor sinus
      drainage could be a possible pathophysiology for the formation of a sinus stone.
      Aspergillosis infection should be considered in the differential diagnosis of a
      radiopaque paranasal sinus lesion. The endoscopic sinus surgery can be a reliable
      and minimally invasive method not only for the removal of the stone, but also for
      the restoration of ventilation and drainage of the diseased sinus.

PMID- 16275419
TI  - Immunotherapeutic strategies in acute lymphoblastic leukaemia relapsing after
      stem cell transplantation.
AB  - Acute lymphoblastic leukaemia (ALL) responds well to chemotherapy and the
      majority of children and a significant proportion of adults are cured of their
      disease after primary therapy. However, a number of patients relapse and
      allogeneic transplantation following conditioning with chemotherapy and
      radiotherapy offers the possibility of long-term survival in a proportion of
      these patients. A significant number of patients with ALL develop disease that is
      refractory to further therapy. The infusion of unmodified donor lymphocytes (DLI)
      following relapse after allogeneic transplantation has been shown to be curative
      in patients with chronic myeloid leukaemia (CML). However, in ALL the success
      rate is much lower. The results of in vitro and limited in vivo studies suggest
      that it may be possible to manipulate lymphocytes from the transplant donor to
      produce cytotoxic T-lymphocytes (CTL) with increased effectiveness in killing
      patients' ALL cells. This may be done in a number of ways. For example, some
      strategies utilise the patients dendritic cells (DC) to present tumour antigens
      to donor lymphocytes and convert them into CTL either by pulsing DC taken in
      remission with ALL cells or lysate, fusing such 'normal' DC with ALL cells or
      using DC cultured from the patient's ALL cells. Other approaches include
      exploiting the expression of leukaemia-specific antigens such as the proteinase
      PR-3 or the zinc finger transcription factor Wilms tumour-1 protein (WT-1) to
      stimulate CTL responses. Alternatively, immunotherapeutic strategies might
      exploit differences in minor histocompatibility antigens such as HA-1 and HA-2
      between donor and recipient. These are expressed solely on haemopoietic cells
      making them suitable targets for donor derived anti-leukaemic cells. In vivo
      studies to date suggest that educated T-cells may have a role to play in the
      treatment of relapsed and refractory ALL in the future.

PMID- 16275420
TI  - Therapeutic potential of embryonic stem cells.
AB  - Nearly 20 years after murine embryonic stem cells (mESC) were isolated, the first
      report of the derivation of human embryonic stem cells (hESC) in 1998 spawned the
      field of hESC research [Evans MJ, Kaufman MH, Establishment in culture of
      pluripotential cells from mouse embryos. Nature 1981; 292 (5819): 154-6; Thomson
      JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from
      human blastocysts. Science 1998; 282 (5391): 1145-7.]. Although this field is
      only in its infancy, hESC represent a theoretically inexhaustible source of
      precursor cells that could be differentiated into any cell type to treat
      degenerative, malignant, or genetic diseases, or injury due to inflammation,
      infection, and trauma. This pluripotent, endlessly dividing cell has been hailed
      as a possible means for treating diabetes, Parkinson's disease, Alzheimer's,
      spinal cord injury, heart failure, and bone marrow failure. But the regenerative
      medicine applications of embryonic stem cells are only one facet of hESC
      therapeutic potential. Human ESC are an invaluable research tool to study
      development, both normal and abnormal, and can serve as a platform to develop and
      test new therapies. In addition to discussing the therapeutic potential of hESC,
      this chapter will cover limitations to using hESC for replacement cell therapy,
      strategies to overcome these limitations, and alternative methods of deriving
      hESC.

PMID- 16275421
TI  - Quantitative measurement of leakage volume and permeability in gliomas,
      meningiomas and brain metastases with dynamic contrast-enhanced MRI.
AB  - The spatial properties and function of the tumor vasculature differ with the
      tumor type and grade. T1-weighted dynamic contrast-enhanced imaging technique
      enables the simultaneous quantification of some functional parameters of the
      vasculature. These are the fractional contrast-enhancing volumes of the tissue
      compartments (blood volume and leakage/extravascular extracellular volume) and
      the exchange parameters (perfusion and permeability). The relatively long
      monitoring duration of 12 min used here made it necessary to divide the
      extravascular extracellular compartment into two subcompartments, a slowly and a
      fast enhancing one with different permeabilities. Forty-one gliomas (WHO grades
      II-IV), six meningiomas and eight distant metastases were investigated. It was
      shown that the technique noninvasively provides information for separating
      different tumor types and characterizing their microenvironment. Fast
      permeability describes vessel permeability and was significantly increased in
      meningiomas as compared with intra-axial tumors. The corresponding volume of the
      fast enhancing compartment was significantly increased in meningiomas compared to
      all gliomas taken together. Slow permeability describes diffusion within the
      extravascular extracellular space and was significantly reduced in low-grade
      gliomas, indicating short diffusion distances. The slowly enhancing extravascular
      extracellular space was found to be increased in high-grade gliomas and distant
      metastases. Blood volume differed significantly among some tumor entities and
      glioma grades. Perfusion was shown to increase linearly with blood volume for
      volumes of up to 20%, flattening out thereafter. The scatter plots of
      extravascular extracellular volume and blood volume were shown to differ among
      the tumor entities.

PMID- 16275422
TI  - Functional magnetic resonance imaging based on SEEP contrast: response function
      and anatomical specificity.
AB  - Functional magnetic resonance imaging based on a non-BOLD-contrast mechanism,
      which we have termed "SEEP" (Signal Enhancement by Extravascular water Protons),
      has previously been demonstrated. Here the reproducibility of areas of activity
      identified with both SEEP and BOLD contrast is assessed in duplicate experiments
      in healthy volunteers, with relatively high resolution (1.6 mm) image data at 1.5
      T. These areas of activity are equally well localized to voxels containing
      primarily gray matter with the two contrast mechanisms. As in previous studies,
      areas of SEEP activity are observed to be immediately adjacent to areas of BOLD
      activity, with very little overlap. The response functions were estimated for
      both SEEP and BOLD contrast, and are observed to be distinct. The peak SEEP
      response is observed to lag the BOLD response by approximately 1 s and to decay
      more slowly with no poststimulus undershoot. Average BOLD signal changes (GE-EPI,
      TE=50 ms) were observed to be 3.4+/-1.2% (mean+/-S.D.), whereas SEEP signal
      changes (SE-EPI, TE=23 ms) were 1.9+/-0.5%, consistent with previous studies
      carried out at 0.2 and 3 T. These observations provide further support for the
      existence of a non-BOLD-contrast mechanism for fMRI, based on changes in
      extravascular spin density.

PMID- 16275423
TI  - Correlation of proton MR spectroscopy and diffusion tensor imaging.
AB  - Proton magnetic resonance spectroscopy ((1)H-MRS) provides indices of neuronal
      damage. Diffusion tensor imaging (DTI) relates to water diffusivity and fiber
      tract orientation. A method to compare (1)H-MRS and DTI findings was developed,
      tested on phantom and applied on normal brain. Point-resolved spectroscopy
      (T(R)/T(E)=1500/135) was used for chemical shift imaging of a supraventricular
      volume of interest of 8 x 8 x 2 cm(3) (64 voxels). In DTI, a segmental spin-echo
      sequence (T(R)/T(E)=5500/91) was used and slices were stacked to reproduce the
      slab used in MRS. The spatial distributions of choline and N-acetylaspartate
      (NAA) correlated to mean fractional anisotropy and apparent diffusion coefficient
      (ADC) for the inner 6 x 6=36 voxels defined in MRS, most notably NAA and ADC
      value (r=-.70, P<.00001; correlation across four subjects, 144 data pairs). This
      is the first association of neuron metabolite contents in volunteers with
      structure as indicated by DTI.

PMID- 16275425
TI  - Magnetic resonance imaging of objects with dipolar-broadened spectra using soft
      excitation pulses.
AB  - Feasibility of acquiring high-resolution 3D NMR images of objects with dipolar
      broadened spectra by using soft excitation pulses is experimentally demonstrated.
      The models are liquid-crystalline phantoms and a pencil eraser. The pulse
      sequence is a standard 3D gradient-echo sequence.

PMID- 16275424
TI  - Pharmacokinetics of lithium in rat brain regions by spectroscopic imaging.
AB  - Lithium (Li) and its salts have been demonstrated to be the most effective drug
      in both acute and prophylactic treatment of bipolar disorder. The exact molecular
      mechanisms and particular target regions accounting for its mood-stabilizing
      effect remain unknown. Knowledge of Li distribution and its regional
      pharmacokinetic properties in the living brain is of value in localizing its
      action in the brain. Pharmacokinetic measurements in different anatomical regions
      of the human brain are not yet available. Limited pharmacokinetic measurements in
      rat brain subvolumes have been performed using atomic absorption technique.
      However, a noninvasive way of estimating the pharmacokinetics in different
      regions of the brain where the drug exerts its beneficial effects would allow
      such methods to be used in the study of patients undergoing Li therapy. Earlier
      (7)Li MR studies on rat brain regions have provided preliminary pharmacokinetic
      information from the whole brain. Using (7)Li MR spectroscopic imaging (SI)
      technology, Li distribution in brain regions of the rat at therapeutic dosages
      has been recently demonstrated by us. Here we report feasibility of local
      pharmacokinetic measurements on brain regions obtained by magnetic resonance SI
      technology. Our results suggest that Li is most active in a region stretching
      from the anterior cingulate cortex and striatum to the caudal midbrain, with
      greatest activity including the preoptic area and hypothalamic region. Some
      activity was seen in prefrontal cortex, but only minimal amounts in the region of
      the cerebellum and metencephalic brainstem.

PMID- 16275426
TI  - A phase rotation scheme for achieving very short echo times with localized
      stimulated echo spectroscopy.
AB  - In a single-voxel stimulated echo localization sequence in magnetic resonance
      spectroscopy, magnetic field gradients are inserted within the echo time (TE) to
      filter signals generated through coherence pathways other than that leading to
      the stimulated echo. There is a significant penalty for these gradients as they
      increase the minimum TE, thereby leading to significant signal loss from spin
      spin relaxation and phase distortions in coupled spin systems. Here, an RF phase
      rotation technique is described for a stimulated echo localization sequence that
      allows removal of the gradients in the TE intervals and, subsequently, reduction
      of the minimum TE to only 6 ms. Experiments carried out on six healthy volunteers
      on a 1.5-T whole-body MR system show a significant signal increase in the
      metabolite concentrations when measured with a 6-ms TE (N-acetyl-aspartate, 12%,
      P=.002; creatine, 15%, P=.04; and glutamate+glutamine, 92%, P=.02) compared to
      concentrations measured with data collected at TEs of 15 and 20 ms.

PMID- 16275427
TI  - Unbiased segmentation of diffusion-weighted magnetic resonance images of the
      brain using iterative clustering.
AB  - Segmentation of diffusion-weighted echo-planar imaging (DW-EPI) is challenging
      because of concerns regarding spatial resolution and distortion. Methods commonly
      used require manual input and often need thresholding measures to segment white
      matter (WM), gray matter (GM) and cerebrospinal fluid (CSF). This may introduce
      operator bias and misclassification error. When comparing patients with a diffuse
      disease process-such as multiple sclerosis (MS)--with healthy controls, although
      information from all images may be biased due to disease effect, this is more so
      if the data set employed to perform segmentation is also used as a measured
      outcome for the study, for example, fractional anisotropy maps. Presented in this
      work is an unbiased method for segmenting DW-EPI data sets using the b=0 and
      single-shot inversion recovery EPI into WM, GM and CSF. The method employs an
      iterative clustering technique to account for partial volume effects and signal
      variation caused by radiofrequency inhomogeneity. The technique is evaluated with
      both real and synthetic brain data and results compared with statistical
      parametric mapping (SPM02). With synthetic brain data, where a gold standard of
      segmentation exists, the presented method showed less misclassification compared
      to SPM02. The unbiased method proposed may provide a more accurate methodology of
      segmentation in the analysis of DWI-EPI images in conditions such as MS.

PMID- 16275428
TI  - Simple design changes to wires to substantially reduce MRI-induced heating at 1.5
      T: implications for implanted leads.
AB  - Reductions in MRI-induced heating at 1.5 T resulting from a simple design change
      to coiled wires were investigated. MRI-induced heating was assessed for two
      different coiled wire forms (length, 26 cm): (1) multi-filar coiled wire form and
      (2) multi-filar coiled wire form having a different coiled pitch, providing an
      air gap spacing between adjacent five-filar coil loops. Each wire had an
      electrode and was insulated to create a lead, similar to that which would be used
      for a medical implant. The wire forms were placed in a gelled-saline-filled
      head/torso phantom and imaged at 1.5 T [whole-body average specific absorption
      rate (SAR), 1.79 W/kg]. Fluoroptic thermometry probes were used to measure
      temperatures at the distal ends of the wires. The experiments demonstrated a
      substantial reduction in MRI-induced heating for the modified wire compared to
      the unmodified wire (i.e., 10.5 degrees C difference observed in one experiment
      and 26 degrees C difference in another). These findings have important
      implications for MRI-induced heating of leads used for medical implants.

PMID- 16275429
TI  - Efficacy of spectral presaturation of inversion recovery in evaluating delayed
      myocardial enhancement.
AB  - OBJECTIVE: Delayed myocardial enhancement is caused by a variety of
      cardiovascular diseases. The extent of the enhanced area has been examined by the
      inversion recovery (IR) method, whereby at the inversion time (TI), normal
      myocardium shows a low signal intensity. In this sequence, as pericardial fat
      shows a very high intensity, a delayed enhancement just below the pericardium may
      be indistinct. To improve the accuracy of delayed myocardial enhancement, we
      employed the spectral presaturation of inversion recovery (SPIR) method.
      MATERIALS AND METHODS: Thirty-five patients with symptoms of cardiovascular
      disease aged between 36 and 80 years old (mean age, 62 years old) were
      investigated. Thirty were men and five were women. Inversion recovery and SPIR
      images were obtained 25 min after initial administration of a gadolinium-based
      contrast material. Each TI, when the signal intensity of the normal myocardium
      was null, was determined by images obtained at serial different TIs. A
      radiologist and a cardiologist examined each image by a consensus reading. The
      extent of myocardial enhancement was described as none, subendocardial,
      transmural and a random pattern in each case. Images were ranked over three
      levels and were based on whether myocardial enhancement could be easily detected
      or whether the contour of the myocardium was visualized precisely. Student's t
      test was conducted to compare the quality of two sequences in all patients and in
      22 patients who showed delayed myocardial enhancement. RESULTS: The imaging
      quality in evaluating delayed myocardial enhancement in all patients was superior
      with IR compared with SPIR, although it was not statistically significant. The
      imaging quality in the patients with delayed myocardial enhancement was similar
      between SPIR and IR. SPIR was superior to the IR sequence in two of the four
      patients who exhibited transmural enhancement. CONCLUSION: SPIR exhibited
      equivalent image quality to IR in evaluating delayed myocardial enhancement. As
      it has the potential advantage in patients with rich adipose tissue surrounding
      the myocardium, it can be an alternative sequence to evaluate myocardial
      viability.

PMID- 16275430
TI  - 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors reduce the risk of
      perioperative stroke and mortality after carotid endarterectomy.
AB  - OBJECTIVE: There is increasing evidence that 3-hydroxy-3-methylglutaryl coenzyme
      A reductase inhibitors (statins) reduce cardiovascular and cerebrovascular events
      through anti-inflammatory, plaque stabilization, and neuroprotective effects
      independent of lipid lowering. This study was designed to investigate whether
      statin use reduces the incidence of perioperative stroke and mortality among
      patients undergoing carotid endarterectomy (CEA). METHODS: All patients
      undergoing CEA from 1994 to 2004 at a large academic medical center were
      retrospectively reviewed. The independent association of statin use and
      perioperative morbidity was assessed via multivariate logistic regression
      analysis. RESULTS: CEA was performed by 13 surgeons on 1566 patients (987 men and
      579 women; mean age, 72 +/- 10 years), including 1440 (92%) isolated and 126 (8%)
      combined CEA/coronary artery bypass grafting procedures. The indication for CEA
      was symptomatic disease in 660 (42%) cases. Six hundred fifty-seven (42%)
      patients received a statin medication for at least 1 week before surgery. Statin
      use was associated with a reduction in perioperative strokes (1.2% vs 4.5%; P <
      .01), transient ischemic attacks (1.5% vs 3.6%; P < .01), all-cause mortality
      (0.3% vs 2.1%; P < .01), and median (interquartile range) length of
      hospitalization (2 days [2-5 days] vs 3 days [2-7 days]; P < .05). Adjusting for
      all demographics and comorbidities in multivariate analysis, statin use
      independently reduced the odds of stroke threefold (odds ratio [95% confidence
      interval], 0.35 [0.15-0.85]; P < .05) and death fivefold (odds ratio [95%
      confidence interval], 0.20 [0.04-0.99]; P < .05). CONCLUSIONS: These data suggest
      that perioperative statin use may reduce the incidence of cerebrovascular events
      and mortality among patients undergoing CEA.

PMID- 16275432
TI  - Surgical vs medical treatment for isolated internal carotid artery elongation
      with coiling or kinking in symptomatic patients: a prospective randomized
      clinical study.
AB  - BACKGROUND: Whether surgically correcting symptomatic carotid elongation with
      coiling or kinking in the absence of an atherosclerotic lesion of the carotid
      bifurcation (isolated elongation) is effective in preventing stroke remains a
      controversial issue. The hypothesis behind this study was that surgical
      correction of symptomatic isolated carotid elongation with coiling or kinking
      could yield better results, in terms of stroke prevention and freedom from late
      stroke or carotid occlusion, than medical treatment. METHODS: We conducted a
      prospective clinical study randomly assigning symptomatic patients with isolated
      carotid elongation to undergo either elective surgery or medical treatment, with
      surgery reserved for any new onset or worsening of symptoms. The follow-up ranged
      from 1 month to 10 years (median, 5.9; mean, 6.2 years) and was obtained for all
      patients. The study end points were perioperative (30-day) stroke and mortality,
      late stroke, and stroke-related death and late carotid occlusions. RESULTS:
      Ninety-two patients were randomly assigned for surgery and 90 for medical
      treatment. Overall, 139 carotid surgical corrections were performed in 129
      patients. All 92 patients in the surgical arm had an elective operation; 10 of
      these patients later developed symptoms on the opposite side (7 hemispheric and 3
      retinal transient ischemic attacks) and had contralateral internal carotid artery
      surgery. An additional 37 patients (41.1%) randomly assigned to medical treatment
      crossed over to the surgical group within a mean of 16.8 months after
      randomization due to new hemispheric symptoms or worsening nonhemispheric
      complaints. There were no perioperative strokes or deaths. The incidence of late
      hemispheric and retinal transient ischemic attacks was significantly lower in the
      surgical than in the medical group, respectively, 7.6% (7 of 92) vs 21.1% (19 of
      90) (P = .01) and 3.2% (3 of 92) vs 12.2% (11 of 90) (P = .03). Late strokes, 2
      (2.2%) of which were fatal, occurred only in the medical group (6 of 90, 6.6%; P
      = .01). Late carotid occlusions also developed only in the medical group (5 of
      90, 5.5%; P = .02). All surgically treated carotid elongations were analyzed
      histologically and 78 (56.%) of 139 showed atypical and typical patterns of
      fibromuscular dysplasia. CONCLUSIONS: The overall results of this trial indicate
      that surgical correction of symptomatic isolated carotid elongations with coiling
      or kinking is better for stroke prevention than medical treatment.

PMID- 16275434
TI  - Cerebral microembolization after protected carotid artery stenting in surgical
      high-risk patients: results of a 2-year prospective study.
AB  - BACKGROUND: This was a prospective single-center study to assess and analyze
      cerebral embolization resulting from carotid artery stenting with neuroprotective
      filter devices in patients considered as poor surgical candidates for surgical
      carotid endarterectomy. METHODS: Fifty-three consecutive patients with an
      internal carotid artery stenosis were treated by placement of carotid Wallstents
      with two different types of temporary distal filter protection devices: the
      Spider filter and the FilterWire. Diffusion-weighted magnetic resonance imaging
      (DWI) of the brain was obtained 24 hours before the procedure and within 5 to 30
      hours after the procedure to detect ischemic brain lesions resulting from the
      procedure. Inclusion criteria were symptomatic (> or =70%) or asymptomatic (> or
      =80%) stenoses in surgical high-risk patients. RESULTS: Two (4%) regressive minor
      strokes occurred. Postprocedural DWI detected new focal ischemic lesions in 21
      patients (40%). The average number of lesions was 5.9 per patient, and the mean
      lesion volume was 1 mL or less in 19 patients (90%). Small differences were found
      in the lesion distribution: homolateral anterior circulation in eight cases
      (15.1%), other vascular territories in seven cases (13.2%), and homolateral
      anterior circulation plus other vascular territories in six cases (11.3%). The
      microembolization risk seemed nonpredictable on the basis of clinical parameters
      and internal carotid artery lesion characteristics. An increased risk in the rate
      of ipsilateral hemispheric embolization has been observed in difficult carotid
      arch implantations (P = .04). CONCLUSIONS: The incidence of new focal ischemic
      lesions detected by DWI is higher than expected on the basis of previous reports.
      Embolization from the aortic arch or common carotid arteries could account for
      most of those events in patients considered as surgical high-risk patients.
      Although 90% of the events were clinically silent, this high rate of
      microembolization raises questions about the possible consequences on cerebral
      cognitive functions.

PMID- 16275436
TI  - Endovascular management of spontaneous carotid artery dissection.
AB  - OBJECTIVE: Despite medical therapy, a subset of patients with spontaneous carotid
      artery dissection (SCD) experience recurrent or progressive symptoms. In this
      study, we assessed the safety and efficacy of endovascular stent angioplasty in
      the treatment of SCD. METHODS: Seven consecutive patients with SCD underwent
      endovascular stent angioplasty of a total of 12 vessels. Indications included the
      presence of a large or enlarging pseudoaneurysm, a contraindication to
      anticoagulation, failure of anticoagulation, and compromised cerebral blood flow.
      RESULTS: Five patients had fibromuscular dysplasia. All patients tolerated the
      procedure well, with no adverse clinical events. All patients showed symptomatic
      improvement on clinical follow-up except for one patient, who had hemorrhagic
      conversion of a pre-existing large ischemic stroke 13 days after intervention; he
      made an eventual recovery to baseline. All stents have remained patent on
      radiologic follow-up. CONCLUSIONS: This study provides additional evidence that
      endovascular stent angioplasty is a safe and effective treatment for SCD in
      patients for whom medical treatment is not adequate.

PMID- 16275438
TI  - A preliminary clinical scale to predict the risk of in-hospital death after
      carotid endarterectomy.
AB  - OBJECTIVE: Carotid endarterectomy (CEA) remains the gold standard for the
      treatment of carotid disease, with mortality rates generally at 0.4% to 1.7%.
      Controversy remains with regards to its role in the treatment of the high-risk
      surgical population. We developed a new clinical scale incorporating weighted
      risk factors into a single numerical score that correlates with the risk of in
      hospital death after CEA. We propose that this tool may serve to prospectively
      identify the high-risk patient. METHODS: We performed a retrospective analysis of
      10 years (1994 to 2003) of the Maryland hospital discharge database. Included in
      the analysis were patients with (1) International Classification of Diseases, 9th
      Revision, Clinical Modification (ICD-9-CM) procedure code 38.12 (endarterectomy
      of the vessels of the head and neck other than intracranial vessels) in the
      primary coding position but not in any secondary position, or (2) Diagnosis Code
      433.00 to 433.91 (occlusion/stenosis, precerebral artery), or (3) the Diagnosis
      Related Group 5 (extracranial vascular procedure). ICD codes representing
      preoperative conditions of the patients were identified and evaluated with
      stepwise regression modeling techniques for association with in-hospital deaths.
      Different regression models were evaluated and compared by discriminative power
      as measured by receiver operating characteristics (ROC) and goodness-of-fit to
      data as measured by r(2) and the Hosmer-Lemeshow statistic. A numeric index
      correlating with the risk of in-hospital death was constructed by rounding the
      correlation coefficients for the statistically significant variables from the
      logistic regression. RESULTS: We identified 23,237 cases. The mean age of
      patients was 70.6 years, with 54.7% male patients. There were 125 in-hospital
      deaths (0.54%). Patient age and four patient medical conditions emerged with
      significant associations with in-hospital deaths after CEA, and their
      relationships can be summarized in a single diagnostic scale: 1 point for age >
      or =75, 2 points for atherosclerosis (ICD code 440), 3 points for cardiomyopathy
      (ICD code 425), 4 points for iron-deficiency anemia (ICD code 280), and 5 points
      for cerebral degeneration (ICD code 331). This scale has moderate discriminative
      power (ROC = 0.67). On average, each point increase on this scale is associated
      with a 1.58-times increase in mortality risk, with score of 6 on the scale
      carrying a mortality risk >5%. CONCLUSIONS: This new 5-item scale, based on
      patient age and past medical history, correlates moderately with the rate of in
      hospital death after CEA. This clinical index may serve to identify high-risk
      patients. Future improvements to this diagnostic scale should focus on the
      diagnostic values of additional laboratory and demographic data.

PMID- 16275440
TI  - Primary closure of the carotid artery is associated with poorer outcomes during
      carotid endarterectomy.
AB  - INTRODUCTION: Arterial endarterectomy and reconstruction during carotid
      endarterectomy (CEA) can be performed in a variety of ways, including standard
      endarterectomy with primary closure, standard endarterectomy with patch
      angioplasty, and eversion endarterectomy. The optimal method of arterial
      reconstruction remains a matter of controversy. The objective of this study was
      to determine the effect of the method of arterial reconstruction during CEA on
      perioperative outcome. METHODS: A retrospective cohort study of consecutive CEAs
      performed by 81 surgeons during 1997 and 1998 in six regional hospitals was
      performed. Detailed clinical data regarding each case and all deaths and nonfatal
      strokes within 30 days of surgery were ascertained by an independent review of
      the inpatient chart, outpatient surgeon record, and the hospitals' administrative
      databases. Two physician investigators--one neurologist and one internist-
      confirmed each adverse event by independently reviewing patients' medical
      records. RESULTS: A total of 1972 CEAs were performed. The mean age of the
      patients was 72.3 years, and 57.2% were male. Preoperative neurologic symptoms
      occurred in 28.7% of cases (n = 566), and the remaining 71.3% were asymptomatic
      before surgery (n = 1406). The method of arterial reconstruction was chosen by
      the surgeon. Primary closure was performed in 11.8% (n = 233), patch angioplasty
      in 69.8% (n = 1377), and eversion endarterectomy in 18.4% (n = 362). There was no
      significant difference in the preoperative symptom status of patients who
      underwent primary closure compared with the other methods of reconstruction
      (72.5% asymptomatic vs 71.1%, p = NS). Primary closure cases were significantly
      more likely to experience perioperative stroke compared with the other closure
      techniques (5.6% vs 2.2%, P = .006). Primary closure cases also had a higher
      incidence of perioperative stroke or death compared with the other closure
      techniques (6.0% vs 2.5%, P = .006). There were no significant differences with
      regard to either perioperative stroke, or perioperative stroke/death noted when
      comparing patch angioplasty with eversion endarterectomy: stroke, 2.2% vs 2.5% (P
      = NS) and stroke/death, 2.5% vs 2.5% (P = NS) respectively. CONCLUSION: It
      appears that primary closure is associated with significantly worse perioperative
      outcomes compared with endarterectomy with patch angioplasty and eversion
      endarterectomy, even when the preoperative symptom status of the patient cohorts
      is equivalent. Although some of its advocates have reported that they can
      properly select appropriate patients for primary closure based on the size of the
      artery and other factors, the data demonstrate that these patients have poorer
      outcomes nonetheless. Primary closure during carotid endarterectomy should
      predominantly be abandoned in favor of either standard endarterectomy with patch
      angioplasty or eversion endarterectomy.

PMID- 16275441
TI  - The safety of carotid endarterectomy in diabetic patients: clinical predictors of
      adverse outcome.
AB  - OBJECTIVES: Patients with diabetes mellitus have been shown to have an increased
      incidence of complications after elective major vascular surgery. The objective
      of this study was to evaluate a large series of diabetic patients undergoing
      carotid endarterectomy (CEA) to determine if outcome differed from nondiabetic
      patients and to examine predisposing factors of poor outcome among diabetic
      patients. METHODS: A retrospective review of a prospectively compiled database
      was performed. From 1992 through 2000, 2151 CEAs were performed at our
      institution. Of these, 507 were in diabetic patients (23.6%), and the remaining
      1644 procedures were in nondiabetic patients (76.4%). RESULTS: Diabetic patients
      were significantly more likely than nondiabetic patients to have hypertension
      (70.8% vs 64.5%, P = .01) and cardiac disease (54.6% vs 49.1%, P = .03). They
      were more likely than nondiabetic patients to be symptomatic before surgery
      (52.5% vs 47.1%, P = .04) and to have sustained a preoperative stroke (21.3% vs
      17.7%, P = .07). No differences were noted in other recorded demographic factors
      or in intraoperative factors between diabetic and nondiabetic patients. Despite
      these differences, diabetic patients had similar perioperative outcomes compared
      with nondiabetic patients, including perioperative myocardial infarction (0.6% vs
      0.4%, P = NS), perioperative death (0.8% vs 0.5%, P = NS), and perioperative
      neurologic events such as transient ischemic attack and stroke (3.2% vs 2.4%, P =
      NS). Among diabetic patients alone, cigarette smoking, general anesthesia, the
      use of a shunt, and the lack of clamp tolerance while under regional anesthesia
      predicted adverse perioperative neurologic outcome, and contralateral occlusion
      was associated with increased perioperative mortality. CONCLUSIONS: Despite an
      increased prevalence of cardiac disease and preoperative neurologic symptoms
      among diabetic patients undergoing CEA, the rates of perioperative cardiac
      morbidity, mortality, and stroke were equal to nondiabetic patients. In contrast
      to nondiabetic patients, current cigarette smoking appeared to predict increased
      adverse neurologic outcomes among diabetic patients, and the presence of
      contralateral occlusion among diabetic patients appeared to predispose them
      towards increased perioperative mortality. The use of a general anesthetic
      appeared to increased perioperative neurologic risk among diabetic patients;
      however, this may be related to surgeon bias in the selection of anesthetic
      technique. Although diabetic patients may have an increase in complications after
      other major vascular surgical procedures, the presence of diabetes mellitus does
      not appear to significantly increase risk.

PMID- 16275442
TI  - Risk factors and prevalence of perioperative cognitive dysfunction in abdominal
      aneurysm patients.
AB  - BACKGROUND: Perioperative delirium is common in high-risk surgery and is
      associated with age, education, preoperative cognitive functioning, pre-existing
      medical conditions, and postoperative complications. We investigated these
      factors as well as lifestyle and demographic variables by using cognitive
      measures that were more sensitive than those used in previous studies. METHODS:
      Extensive medical and demographic data were collected on 102 patients between 41
      and 88 years of age to identify comorbidities and lifestyle considerations
      preoperatively. Elective abdominal aortic aneurysm surgery was performed under
      combined general/epidural anesthesia with postoperative epidural analgesia. A
      battery of sensitive, cognitive measures was administered preoperatively, at the
      time of discharge from hospital, and 3 months postoperatively. Symptoms of
      delirium were assessed during the first 6 postoperative days using Diagnostic and
      Statistical Manual of Mental Disorders-4th Edition criteria. Intraoperative and
      postoperative data, including medications, vital signs, conduct of the surgery
      and anesthesia, complications, and details of pain control, were collected.
      RESULTS: Delirium occurred in 33% of the patients during the first 6 days after
      surgery. Longer duration of delirium was related to lower education, preoperative
      depression, and greater preoperative psychoactive medication use. Characteristics
      of the surgery and hospital stay were unrelated to the development of delirium.
      Patients who were diagnosed with delirium had lower cognitive scores during each
      of the three assessment periods, even when controlling for age and education.
      Logistic regression analysis indicated that the most powerful preoperative
      predictors of delirium were number of pack years smoked (P = .001), mental status
      scores (P = .003), and number of psychoactive medications (P = .005). CONCLUSION:
      A significant proportion of patients undergoing elective abdominal aortic
      aneurysm repair are susceptible to the development of delirium and are at risk
      for cognitive dysfunction after surgery. Our findings have implications for
      promoting long-term lifestyle changes, including smoking cessation and improved
      management of mental health as risk-reduction strategies.

PMID- 16275443
TI  - The lifetime prevalence of abdominal aortic aneurysms among siblings of aneurysm
      patients is eightfold higher than among siblings of spouses: an analysis of 187
      aneurysm families in Nova Scotia, Canada.
AB  - BACKGROUND: Abdominal aortic aneurysms (AAAs) are frequently familial. The aim of
      this study was to compare the prevalence of AAA among the siblings of AAA
      patients with that in the spouses' siblings. METHODS: The siblings of 375 AAA
      patients and the siblings of the spouses of the AAA patients were included in
      this study and offered ultrasonography screening for AAA. Participants were asked
      to complete a questionnaire to collect demographic and general health
      information. Statistical analysis was done with Fisher's exact test. Odds ratios
      and 95% confidence intervals were also calculated. RESULTS: Abdominal
      ultrasonography examinations were done for 309 individuals. The results indicated
      that 11 (11.2%) of 98 brothers of AAA patients, 4 (2.7%) of 147 sisters, and none
      of the 64 siblings of the spouses of the AAA patients were found to have an AAA.
      Combining the information from the ultrasonography screening and medical records
      on already known cases of AAA in these families, altogether 29.0% (44/152) of the
      brothers of AAA patients, 11.1% (20/181) of the sisters of AAA patients, and 2.3%
      (2/88) of the siblings of the spouses had an AAA. CONCLUSION: There was a
      significant difference between the siblings of the AAA patients and those of the
      spouses both in the frequency of AAA detected by ultrasonography screening and in
      the overall prevalence of AAA. The overall prevalence of AAA in the siblings of
      AAA patients was about eight times that observed among the siblings of their
      spouses (19.2% vs 2.3%). These findings confirmed previous reports on high
      prevalence of AAA among siblings of AAA patients and emphasized the importance of
      an ultrasonography screening program for siblings of AAA patients.

PMID- 16275444
TI  - A personal experience with factors influencing survival after elective open
      repair of infrarenal aortic aneurysms.
AB  - OBJECTIVE: To investigate risk factors that influence survival after open
      abdominal aortic aneurysm (AAA) repair in all elective patients treated by a
      single surgeon at a tertiary referral center. METHODS: The series includes 855
      asymptomatic infrarenal AAAs in 732 men (86%) and 123 women with median ages of
      69 and 71 years, respectively. Noninvasive myocardial imaging (n = 325), coronary
      arteriography (n = 418), or both were performed before surgery in 687 patients
      (80%), and 100 patients (15%) underwent preliminary coronary artery bypass
      grafting (n = 78) or percutaneous transluminal coronary angioplasty (n = 22)
      before their AAA procedures. Survival was assessed by using logistic regression
      analysis, proportional hazards models, and Kaplan-Meier estimations. RESULTS: The
      operative mortality rate was 2.5%, ranging only from 1.8% to 2.8% since 1980.
      Late survival rates (70% at 5 years, 36% at 10 years, and 16% at 15 years) also
      remained remarkably similar during five arbitrary intervals comprising the entire
      study period. On multivariable analysis, overall mortality rates were adversely
      affected by older age (P < .001), increased creatinine levels (P < .001),
      straight aortic replacement grafting (P < .001), larger aneurysm diameter (P =
      .036), and chronic obstructive pulmonary disease (P = .012). The risk for any
      early or late death was favorably influenced by preliminary coronary artery
      bypass grafting or percutaneous transluminal coronary angioplasty (hazard ratio,
      0.76; 95% confidence interval, 0.59-0.98; P = .035) even when a separate
      multivariable model was fit to accommodate nine other patients who also had
      preliminary coronary intervention but developed symptomatic AAAs before elective
      repair could be performed (hazard ratio, 0.78; 95% confidence interval, 0.61
      0.99; P = .044). CONCLUSIONS: Patient age and medical risk factors determine
      survival after open AAA repair to a very similar degree irrespective of the era
      when the operation is performed. In this particular series, preliminary coronary
      intervention seemed to benefit patients with severe coronary artery disease.

PMID- 16275445
TI  - Total laparoscopic versus conventional abdominal aortic aneurysm repair: a case
      control study.
AB  - PURPOSE: This study was designed to identify differences in the per- and
      postoperative outcomes between total laparoscopic and open surgical repair of
      abdominal aortic aneurysms (AAA). METHODS: We reviewed 30 patients who underwent
      total laparoscopic AAA repair between July 2003 and December 2004 (group I). This
      group was matched in a case-control fashion by AAA morphology and American
      Society of Anesthesiologists class with a group of 30 patients who underwent
      conventional AAA repair between April 1997 and May 2004 (group II). Proportions
      and categoric data were compared with a chi(2) test. Continuous data were
      compared with a Mann-Whitney test. RESULTS: The two groups had comparable
      characteristics of age and cardiovascular risk factors. The number of tube and
      bifurcated grafts was 13 for group I and 17 for group II. Median operative time
      was 255 minutes (range, 170 to 410 minutes) in group I and 200 minutes (range,
      130 to 410) in group II (P <.001). Median aortic clamping time was 80 minutes
      (range, 35 to 110 minutes) in group I and 50 minutes (range, 24 to 150 minutes)
      in group II (P < .0001). Total blood loss was 1600 mL (range, 400 to 4000 mL) for
      group I vd 1000 mL (range, 100 to 2900) for group II (P < .01). The mortality
      rate was 3.3% for group I (1 patient) vs 6.6% (2 patients) for group II (NS).
      There were no significant differences between the two groups in terms of
      postoperative systemic complications (23.3% vs 30%, NS) and local and vascular
      complications (10% vs 3.3%). Duration of ileus (2 vs 3 days, P < .05), return to
      normal diet (4 vs 8 days, P < .0001), day of ambulation (3 vs 4 days, P < .05)
      and dose of narcotics (3.5 mg vs 28.5 mg, P < .05) were significantly lower in
      group I. Median length of intensive care unit stay was similar between the two
      groups (48 hours). Median hospital stay was lower in group I but without
      significant differences with group II (9 vs 11 days, NS). CONCLUSION: This case
      control study provides preliminary results that short-term outcomes of total
      laparoscopic AAA repair are comparable with those of open surgery. Peroperative
      data demonstrate that laparoscopy is more technically demanding than open repair.
      However, the technical challenge of laparoscopy does not worsen the postoperative
      course.

PMID- 16275447
TI  - Follow-up costs increase the cost disparity between endovascular and open
      abdominal aortic aneurysm repair.
AB  - OBJECTIVE: This study compared the hospital and follow-up costs of patients who
      have undergone endovascular (EVAR) or open (OR) elective abdominal aortic
      aneurysm repair. METHODS: The records of 195 patients (EVAR, n = 55; OR, n = 140)
      who underwent elective aortic aneurysm repair between 1995 and 2004 were
      reviewed. Primary costing data were analyzed for 54 EVAR and 135 OR patients.
      Hospital costs were divided into preoperative, operative, and postoperative
      costs. Follow-up costs for EVAR patients were recorded, with a median follow-up
      time of 12 months. RESULTS: Mean preoperative costs were slightly higher in the
      EVAR group (AU $961/US $733 vs AU $869/US $663; not significant). Operative costs
      were significantly higher in the EVAR group (AU $16,124/US $12,297 vs AU $6077/US
      $4635; P < .001); this was entirely due to the increased cost of the endograft
      (AU $10,181/US $7,765 for EVAR vs AU $476/US $363 for OR). Postoperative costs
      were significantly reduced in the EVAR group (AU $4719/US $3599 vs AU $11,491/US
      $8,764; P < .001). Total hospital costs were significantly greater in the EVAR
      group (AU $21,804/US $16,631 vs AU $18,437/US $14,063; P < .001). The increase in
      total hospital costs was due to a significant difference in graft costs, which
      was not offset by reduced postoperative costs. The average follow-up cost per
      year after EVAR was AU $1316/US $999. At 1 year of follow-up, EVAR remained
      significantly more expensive than OR (AU $23,120/US $17,640 vs AU $18,510/US
      $14,122; P < .001); this cost discrepancy increased with a longer follow-up.
      CONCLUSIONS: EVAR results in significantly greater hospital costs compared with
      OR, despite reduced hospital and intensive care unit stays. The inclusion of
      follow-up costs further increases the cost disparity between EVAR and OR. Because
      EVAR requires lifelong surveillance and has a high rate of reintervention, follow
      up costs must be included in any cost comparison of EVAR and OR. The economic
      cost, as well as the efficacy, of new technologies such as EVAR must be addressed
      before their widespread use is advocated.

PMID- 16275448
TI  - Detection of aortic graft infection by fluorodeoxyglucose positron emission
      tomography: comparison with computed tomographic findings.
AB  - OBJECTIVE: Radionuclide imaging with fluorodeoxyglucose (FDG) and positron
      emission tomography (PET) has been proposed for the identification of vascular
      graft infection; however, its accuracy has not been determined. We performed this
      prospective study to compare the usefulness of FDG-PET in the assessment of
      vascular graft infection relative to computed tomography (CT). METHODS: FDG-PET
      was performed for 33 consecutive patients with a suspected arterial prosthetic
      graft infection. The PET images were then assessed visually in terms of the
      density of uptake. In cases with positive uptake, the pattern of accumulation was
      also defined, such as focal or diffuse uptake. We compared the diagnostic
      efficiency of PET with contemporaneous CT in detection of infection of the
      arterial prosthetic graft. RESULTS: On the basis of the surgical,
      microbiological, and clinical follow-up findings, the aortic grafts were
      considered infected in 11 patients and not infected in 22 patients. Although the
      sensitivity of PET (91%) was higher than that of CT (64%), its specificity (64%)
      was lower than that of CT (86%). When focal uptake was set as the positive
      criterion in FDG, the specificity and positive predictive value of PET for the
      diagnosis of aortic graft infection improved significantly to 95% (P < .05 for
      both). CONCLUSIONS: Although both techniques are useful in evaluation of patients
      with suspected aortic graft infection, using the characteristic FDG uptake
      pattern described previously as a diagnostic criterion made the efficacy of FDG
      superior to that of CT in the diagnostic assessment of patients with suspected
      aortic graft infection.

PMID- 16275450
TI  - Contemporary results of angioplasty-based infrainguinal percutaneous
      interventions.
AB  - INTRODUCTION: Although lower-extremity bypass grafting has been the gold standard
      for infrainguinal revascularization, endovascular therapies have been
      increasingly applied to avoid operative morbidities. This study addresses the
      initial results of an implementation of infrainguinal percutaneous transluminal
      angioplasty (PTA) performed by vascular surgeons to treat lower-extremity
      ischemia. METHODS: From January 2002 to July 2003, 95 consecutive patients
      presenting with the spectrum of lower-extremity ischemic manifestations, in whom
      infrainguinal PTA was the initial choice of treatment, were assessed for
      treatment efficacy by clinical and noninvasive evaluation. Study end points of
      angiographic, hemodynamic, and clinical successes (Society of Vascular Surgery
      reporting standards) were recorded, and variables associated with ischemic
      category improvement were analyzed by univariate and multivariate analysis.
      During the same study interval, 87 patients underwent bypass grafting (not
      further considered). RESULTS: PTA was used to treat 100 limbs in 95 consecutive
      patients: 63 limbs (63%) had femoropopliteal PTA, 17 limbs (17%) had
      tibioperoneal PTA, and 20 limbs (20%) had multilevel PTA. Tissue-threatening
      ischemia was present in 47% of patients, and 53% were treated for claudication.
      Complications (no mortality) included one myocardial infarction (1%) and two
      access site hematomas (2%). Angiographic and hemodynamic success (a .10 increase
      in ankle-brachial index) was obtained in 97% and 90% of the treated limbs,
      respectively. With a mean follow-up of 14 months, clinical success was obtained
      in 85% of the treated limbs, and limb salvage for critical ischemia was achieved
      in 75% (30/40 limbs). Of the PTA failures, five patients (5%) underwent bypass
      grafting, and five patients (5%) underwent major amputation because of no further
      reconstructive options or extensive necrosis. Insulin-dependent diabetes mellitus
      (risk ratio [RR], 3.1; 95% confidence interval [CI], 1.1 to 8.7, P = .02), poor
      runoff into the foot (RR, 3.7; 95% CI, 1.6 to 8.6, P = .001), and renal
      insufficiency (serum creatinine >1.5 mg/dL) (RR, 3.7; 95% CI, 1.8 to 7.6, P =
      .001) were predictive of PTA failure. CONCLUSION: Infrainguinal percutaneous
      transluminal angioplasty for lower-extremity ischemia is feasible, safe and
      provides acceptable hemodynamic and clinical results. PTA will become the initial
      treatment for most patients requiring lower-extremity revascularization.

PMID- 16275449
TI  - Age-related increase in wall stress of the human abdominal aorta: an in vivo
      study.
AB  - BACKGROUND: The regulation of wall stress in the abdominal aorta (AA) of humans
      might be of specific interest, because the AA is the most common site for
      aneurysm formation in which wall stress seems to be an important
      pathophysiological factor. We studied the age-related changes in wall stress of
      the AA in healthy subjects, with the common carotid artery (CCA) as a comparison.
      METHODS: A total of 111 healthy subjects were examined with B-mode
      ultrasonography to determine the lumen diameter and intima-media thickness (IMT)
      in the AA and the CCA. RESULTS: Aortic IMT was affected by age in men and by both
      age and lumen diameter in women. Carotid IMT was affected by age and pulse
      pressure in both men and women. Wall stress was higher in the AA than in the CCA
      (P < .001), and men had higher wall stress than women in both the AA (P < .001)
      and the CCA (P < .05). Furthermore, wall stress was constant during life in the
      CCA of men and women and in the AA of women. In the male aorta, however, wall
      stress increased with age (P < 0.01). CONCLUSIONS: Arterial diameters increase
      with age, and a compensatory thickening of the arterial wall prevents the
      circumferential wall stress from increasing. However, this compensatory response
      is insufficient in the male AA and results in an increase in stress with age.
      These findings might explain the propensity for aneurysms to develop in the AA of
      men.

PMID- 16275451
TI  - Intermittent pneumatic compression of the foot and calf improves the outcome of
      catheter-directed thrombolysis using low-dose urokinase in patients with acute
      proximal venous thrombosis of the leg.
AB  - OBJECTIVE: Catheter-directed thrombolysis (CDT) is a promising treatment of acute
      proximal deep vein thrombosis (DVT) to prevent the postthrombotic syndrome by
      early removal of thrombus. During CDT for DVT patients, the calf muscle pump is
      compromised because of immobility. Intermittent pneumatic compression (IPC) can
      be used to increase venous flow during bed rest. The CDT with IPC may lyse venous
      thrombus better than CDT alone. The purpose of this study was to evaluate the
      efficiency and safety of IPC during CDT for DVT using low-dose urokinase.
      METHODS: Twenty-four patients with proximal DVT confirmed by duplex
      ultrasonography underwent CDT alone (10 cases) and CDT with IPC and a temporary
      inferior vena cava filter (14 cases) for 3 to 6 days. Pulmonary emboli (PEs) were
      assessed by pretreatment and posttreatment pulmonary angiogram or spiral computed
      tomography of the chest, and in the CDT/IPC patients, a posttreatment inferior
      vena cavogram was performed. The initial results were evaluated by venogram
      immediately after CDT, and the late results were evaluated by venous disability
      score and duplex ultrasonography 6 to 36 months after treatment. RESULTS: There
      was no symptomatic PE in either group. In CDT with IPC, one new asymptomatic PE
      was found, but there was no large thrombus in the inferior vena cava. The initial
      thrombolytic results of CDT with IPC were better than those of CDT alone (five
      cases of complete lysis in the CDT/IPC group and none in the CDT alone group). In
      the follow-up, the deep veins were patent and competent in 43% (6/14) in the
      CDT/IPC group, compared with 17% (1/6) in the CDT-alone group. The venous
      disability score showed that the CDT/IPC group had less disability than the CDT
      alone group. CONCLUSIONS: This pilot study showed that adding IPC to CDT using
      low-dose urokinase for DVT treatment of the leg resulted in better early and late
      outcomes compared with CDT alone and was not associated with an increased risk of
      symptomatic PEs.

PMID- 16275452
TI  - Keyhole technique for autologous brachiobasilic transposition arteriovenous
      fistula.
AB  - BACKGROUND: Autologous brachiobasilic transposition arteriovenous fistulas (AVFs)
      are desirable but require long incisions and extensive surgical dissection. To
      minimize the extent of surgery, we developed a catheter-based technique that
      requires only keyhole incisions and local anesthesia. METHODS: The technique
      involves exposure and division of the basilic vein at the elbow. A guidewire is
      introduced into the vein, and a 6F "push catheter" is advanced over the guidewire
      and attached to the vein with sutures. Gently pushing the catheter proximally
      inverts, or intussuscepts, the vein. Side branches that are felt as resistances
      when pushing the catheter forward are localized, clipped, and divided under
      direct vision. Throughout the procedure, the endothelium always remains
      intraluminal. The basilic vein is externalized at the axilla without dividing it
      proximally and is tunneled subcutaneously, where it is anastomosed to the
      brachial artery. RESULTS: Thirty-two patients underwent the procedure--31 as
      outpatients. The mean duration of operation was less than 90 minutes. All
      patients tolerated the procedure well, and 31 required only intravenous sedation
      and local anesthesia. At a mean follow-up of 8 months, the primary patency rate
      of AVFs in patients with basilic vein diameters of 4 mm or more on preoperative
      duplex ultrasonography was 80%, vs 50% for those with vein diameters less than 4
      mm. Overall, 78% of patent AVFs were being successfully accessed and 22% were
      still maturing at last follow-up. CONCLUSIONS: Autologous brachiobasilic
      transposition AVFs can be created by using catheter-mediated techniques that
      facilitate the mobilization and tunneling of the basilic vein through small
      incisions. Medium-term data suggest that the inversion method results in
      acceptable maturation and functionality of AVFs created with this technique.

PMID- 16275453
TI  - Outcome after autogenous brachial-basilic upper arm transpositions in the post
      National Kidney Foundation Dialysis Outcomes Quality Initiative era.
AB  - BACKGROUND: The Dialysis Outcomes Quality Initiative (DOQI)-inspired push to
      create autogenous fistulas has led to a resurgence of interest in basilic vein
      transposition as an autogenous access conduit. We reviewed our experience with
      autogenous brachial-basilic upper arm transpositions (BTX) to clarify current
      maturation and patency rates and provide realistic expectations for a tertiary
      referral vascular practice. METHODS: We follow an aggressive "all-autogenous"
      policy with regard to dialysis access and recommend BTX when all cephalic options
      are exhausted. Prosthetic grafts are not attempted unless all upper extremity
      veins are unusable. The records of all patients undergoing autogenous basilic and
      brachial vein upper arm transpositions for hemodialysis access between April 2001
      and December 2004 were retrospectively evaluated. Mean follow-up was 10 months
      (range, 0 to 38 months). RESULTS: Eighty-seven patients underwent 100 basilic and
      3 brachial vein transpositions. Most of the patients were already receiving
      hemodialysis (83%), with a mean of 1.1 (range, 0 to 4) previous access attempts.
      Perioperative complications included 1 death secondary to a myocardial
      infarction, 7 hematomas (4 requiring reoperation), and 6 infections (2 requiring
      reoperation). Steal syndrome developed in five patients. Maturation rate was 79%.
      Functional primary and secondary patency rates were 23% +/- 5% and 47% +/- 6% at
      1 year and 11% +/- 5% and 40% +/- 10% at 2 years, respectively (mean +/- SE). The
      most common causes of failure for a matured fistula were stenosis within the body
      of the basilic vein (44%) followed by central venous outflow stenosis (20%). No
      preoperative variable, including gender, age, diabetes mellitus, presence of
      ipsilateral hemodialysis catheter, number of previous access attempts, maximal or
      minimal vein diameter, or obesity, had a significant impact on rate of maturation
      or long term patency. CONCLUSIONS: In our experience, autogenous brachial-basilic
      upper arm transposition fistulas have initial maturation rates that exceed DOQI
      guidelines, but disappointing short- to medium-term patency rates. Although these
      outcomes were obtained within the context of an aggressive all-autogenous policy,
      the poor durability of these transpositions should prompt further investigation
      of current access algorithms.

PMID- 16275454
TI  - Improvement in the visualization of superficial arm veins being evaluated for
      access and bypass.
AB  - OBJECTIVES: Duplex ultrasound mapping of arm veins is being performed with
      increasing frequency. Unlike ultrasound testing in other areas, this has never
      been subjected to a gold standard invasive test to determine accuracy. Duplex
      mapping appears to have a good predictive value whenever large veins are
      demonstrated preoperatively, but its ability to accurately measure minimum-sized
      veins is unproven. In this study, we compared diameter measurements obtained
      under six different conditions and used the maximum diameter as the comparison
      gold standard. METHODS: A 12-MHz linear probe was used to measure the cephalic
      and basilic vein cross-sectional diameters at the wrist level in 24 normal
      volunteers under the following conditions: (1) resting supine with a room
      temperature of 23 degrees to 24 degrees C, (2) supine with a tourniquet inflated
      to 65 mm Hg, (3) sitting with the arm dangling, (4) sitting with a tourniquet,
      (5) sitting after a 2-minute immersion in warm water (44 degrees C), and (6) same
      with tourniquet. Half the subjects underwent the protocol in a different order.
      RESULTS: Vein diameters were significantly larger after submersion in warm water
      compared with supine (P < .05, pair-wise multiple comparison procedure, Student
      Newman-Keuls method). Assuming the sitting position (from supine) resulted in a
      decreased arm vein diameter 58% of the time. In 25% of the normal subjects, the
      cephalic vein size was <2 mm, which increased to >2 mm after warming. All
      subjects had either a cephalic or a basilic vein at the wrist that was >3.1 mm
      after warming. CONCLUSION: Use of warm water immersion before vein diameter
      measurement in a sitting position, without a tourniquet, will result in
      significantly larger diameter findings in normal arm veins. These diameters are
      likely to more closely resemble the venous diameter after distension with
      arterial pressure. Further studies are needed to see if warming in patients could
      result in increased utilization of autogenous arm vein for dialysis access and
      bypass.

PMID- 16275455
TI  - Noninvasive measurement of aortic aneurysm sac tension with vibrometry.
AB  - OBJECTIVE: Currently, the risk of aneurysm sac rupture after endovascular
      abdominal aortic aneurysm repair (EVAR) is estimated by using a group of anatomic
      variables. Available techniques for pressure monitoring include either direct
      measurement using catheter-based techniques or indirect measurement requiring
      implantation of a pressure sensor during aneurysm repair. None of these methods
      is without limitations. Radiation pressure, such as that generated by a modulated
      ultrasound (US) beam, can induce surface vibration at a distance. The velocity of
      the resulting surface waves depends on the tensile stress of the vibrated
      surface. By measuring the change in wave velocity, it is possible to detect the
      change in tensile stress and calculate the pressure through the vibrated surface.
      We tested this concept in an in vitro aneurysm model. METHODS: Rubber tubes and
      explanted porcine abdominal aortas were used to model an aneurysm sac. The
      surface of the model was vibrated with an amplitude-modulated US beam. The
      resulting motion was detected either by reflected laser light or by Doppler US.
      The phase of the propagating wave was measured to assess changes in velocity with
      different pressures. RESULTS: Increasing hydrostatic pressure in the rubber model
      correlated well with the cumulative phase shift (R(2) = 0.96-0.99; P < .0001). By
      using a pump to generate dynamic pressure (between 110 and 200 mm Hg), the
      cumulative phase shift correlated well with the square of the mean pressure (R(2)
      = 0.92; P < .0001); however, the correlation with pulse pressure was poor (24-36
      mm Hg; r = 0.38; P < .02). In the porcine in vitro aortic sac model, the
      cumulative phase shift detected with both laser (r = 0.94-0.99; P < .0001) and
      Doppler (r = 0.96-0.99; P < .0001) correlated well with the aneurysm pressure.
      CONCLUSIONS: Application of vibrometry for noninvasive measurement of aortic
      aneurysm sac tension is feasible in an in vitro setting. The concept of
      vibrometry may be used to detect endotension noninvasively after EVAR. Vibrometry
      may also be used to estimate wall stress in native aneurysms, and it may predict
      the risk of aneurysm rupture. CLINICAL RELEVANCE: Vibrometry may offer a
      technique for completely noninvasive monitoring of aneurysm sac pressure after
      EVAR. Vibrometry is based on the following principles: radiation pressure, such
      as that generated by modulated US, can induce surface vibration at a distance; by
      measuring the change in wave velocity of vibration, it is possible to detect
      changes in tensile stress and calculate the pressure through the vibrated
      surface. We tested this concept in an in vitro model and found that application
      of vibrometry for noninvasive measurement of aortic aneurysm sac tension is
      feasible. Vibrometry may also be used to estimate wall stress in native
      aneurysms.

PMID- 16275456
TI  - Human factors as a source of error in peak Doppler velocity measurement.
AB  - OBJECTIVE: The study was conducted to assess the error and variability that
      results from human factors in Doppler peak velocity measurement. The positioning
      of the Doppler sample volume in the vessel, adjustment of the Doppler gain and
      angle, and choice of waveform display size were investigated. We hypothesized
      that even experienced vascular technologists in a laboratory accredited by the
      Intersocietal Commission for Accreditation of Vascular Laboratories make
      significant errors and have significant variability in the subjective adjustments
      made during measurements. METHODS: Problems of patient variability were avoided
      by having the four technologists measure peak velocities from an in vitro
      pulsatile flow model with unstenosed and 61% stenosed tubes. To evaluate
      inaccurate angle and sample volume positioning, a probe holder was used in some
      of the experiments to fix the Doppler angle at 60 degrees. The effect of Doppler
      gain was studied at three settings--low, ideal, and saturated gains--that were
      standardized from the ideal level chosen by consensus amongst the technologists.
      Two waveform display sizes were also investigated. Peak velocity measurement was
      assessed by comparison with true peak velocities. For each variable studied,
      average peak velocities were calculated from the 10 measurements made by each
      technologist and used to find the percent error from the true value, and the
      coefficient of variation was used to measure the variability. RESULTS: Doppler
      angle, sample volume placement, and the Doppler gain were the most significant
      sources of error and variability. Inaccurate angle and placement increased the
      variability in measurements from 1% to 2% (range) to 4% to 6% for the straight
      tube and from 1% to 2% to 3% to 9% for the 61% stenosis. The peak velocity error
      was increased from 9% to 13% to 7% to 28% for the stenosis. Both measurement
      error and variability were strongly dependent on the Doppler gain level. At low
      gain, the error was approximately 10% less than the true value and at saturated
      gain, 20% greater. The display size only affected measurements from the stenosed
      tube, increasing the error from 9% to 13% to 15% to 24%. CONCLUSIONS: Major
      factors affecting Doppler peak velocity measurement error and variability were
      identified. Inaccurate angle and sample volume placement increased the
      variability. The presence of a stenosis was found to increase the measurement
      errors. The error was found to depend on the Doppler gain setting, with greater
      variability at low and saturated gains and on the display size with a stenosis.
      CLINICAL RELEVANCE: Doppler ultrasound peak velocity measurements are widely used
      for the diagnostic assessment of the severity of arterial stenoses. However, it
      is known that these measurements are often in error. We have identified
      subjective human factors introduced by the technologist and assessed their
      contribution to peak velocity measurement error and variability. It is to be
      hoped that by understanding this, improvements in the machine design and
      measurement methods can be made that will result in improved measurement accuracy
      and reproducibility.

PMID- 16275457
TI  - Rapamycin-coated expanded polytetrafluoroethylene bypass grafts exhibit decreased
      anastomotic neointimal hyperplasia in a porcine model.
AB  - OBJECTIVE: We tested the hypothesis that rapamycin coated onto, and eluted from,
      expanded polytetrafluoroethylene (ePTFE) grafts would diminish neointimal
      hyperplasia in a porcine model. METHODS: Rapamycin (also called sirolimus) was
      coated onto the luminal surface of 6-mm-internal-diameter thin-walled ePTFE
      grafts by using an adhesive polymer that allows timed release of the drug. An
      adhesive polymer that allows timed release of rapamycin from ePTFE was developed
      with commercially available chemicals and applied on 6-mm ePTFE grafts. Graft
      integrity was characterized by scanning electron microscopy, and rapamycin levels
      were quantified by using high-performance liquid chromatography. Twenty-two
      mongrel pigs were randomized into three groups: untreated ePTFE (n = 6), adhesive
      only coated ePTFE (n = 6), or adhesive- and rapamycin-coated ePTFE (n = 10). End
      to-side unilateral aortoiliac bypasses were performed by using 6-mm-internal
      diameter ePTFE grafts and standardized anastomotic lengths. Unilateral end-to
      side aortoiliac ePTFE grafts (6-mm internal diameter) were inserted by using
      polypropylene sutures, 6-0 proximally and 7-0 distally; all anastomoses were 12
      mm long. All animals received aspirin (325 mg orally) daily. All animals were
      given oral aspirin (325 mg) daily beginning on the day before surgery. At 28
      days, the animals were killed, and the grafts were explanted in continuity with
      the adjacent aortic cuff and the outflow iliac artery. Variables compared between
      groups included graft patency, distal anastomotic length and cross-sectional
      narrowing, and intimal thickness at the arterial-graft junction indexed to the
      adjacent graft thickness. Microscopic analysis was performed with hematoxylin and
      eosin and Masson trichrome stains on paraffin sections. A pathologist blinded to
      experimental groups graded sections for collagen deposition, neointima formation,
      inflammatory cellular infiltrates, medial necrosis, and aneurysmal degeneration.
      RESULTS: All animals survived until they were killed without clinical evidence of
      limb ischemia or graft infection. Preplanned t tests in the context of one-way
      analysis of variance showed no difference in outcome measures between the
      untreated ePTFE and adhesive-only coated ePTFE groups; therefore, they were
      combined in further comparisons with the adhesive- and rapamycin-coated ePTFE
      group. The Rapamycine eluting expanded polytetrafluoroethylene group had longer
      anastomoses (85.6% vs 60.6% of the initial anastomotic length maintained; P <
      .0001) and less cross-sectional narrowing in the outflow graft (16.2% vs 28.5%; P
      = .0007) when compared with the other two groups by using two-tailed Student t
      tests. There was no evidence of medial necrosis or aneurysmal degeneration. All
      patent grafts had complete endothelialization on hematoxylin and eosin sections.
      Rapamycin was detectable and quantifiable in the arterial wall at 28 days after
      implantation. CONCLUSIONS: Rapamycin can be coated onto and eluted from ePTFE by
      using a nonionic polymer and a simple coating technique. At 4 weeks after
      implantation, the rapamycin-eluting ePTFE grafts demonstrate gross, pathologic,
      and morphometric features of diminished neointimal hyperplasia when compared with
      non-drug-eluting ePTFE. Four weeks after implantation in a porcine model,
      rapamycin-eluting ePTFE grafts demonstrated gross, pathologic, and morphometric
      features of diminished neointimal hyperplasia when compared with untreated and
      adhesive-only coated ePTFE grafts. CLINICAL RELEVANCE: Rapamycin-eluting ePTFE
      grafts decrease neointimal hyperplasia in a porcine model. Further studies are
      needed to evaluate whether patency will be improved. Rapamycin-eluting ePTFE
      grafts may allow the use of prosthetic grafts in situations in which autologous
      vein is unavailable and in which neointimal hyperplasia is pronounced, such as in
      small-diameter (<6-mm) vessels typical of infrapopliteal interventions.

PMID- 16275458
TI  - Preservation of infected and exposed vascular grafts using vacuum assisted
      closure without muscle flap coverage.
AB  - The most widely used techniques for graft preservation after localized graft
      infections are muscle flap closure or antibacterial dressings and irrigations
      after debridement. Vacuum assisted closure (VAC) has been increasingly used for
      complex wounds in vascular surgery, including groin infections, but not directly
      on exposed bypass grafts as a stand-alone technique. We used the VAC system after
      wound debridement in four patients with fully exposed synthetic bypass grafts who
      were too unstable or risky for further operative interventions. Mean duration of
      VAC use was 22.8 days (range, 6 to 53 days), with time to total wound closure of
      30 to 63 days (mean, 41 days). There were no reinfections with 11 to 25 months'
      follow-up (mean, 18.3 months). For high-risk surgical patients with a fully
      exposed infected prosthetic vascular graft, VAC therapy along with aggressive
      debridement and antibiotic therapy may be an effective alternative to current
      management strategies.

PMID- 16275459
TI  - Surgical management of acute carotid thrombosis after carotid stenting: a report
      of three cases.
AB  - We report three cases of symptomatic acute carotid thrombosis occurring after
      carotid artery stenting (CAS). CASE 1: A patient presented with crescendo
      transient ischemic attacks on the second day after CAS. Ultrasound images
      demonstrated incomplete in-stent thrombosis due to plaque protrusion. The urgent
      surgical procedure consisted of stent removal and carotid thromboendarterectomy.
      CASE 2: A case of complete thrombosis of a carotid stent occurred 4 days after
      implantation in a patient with essential thrombocythemia diagnosed by chance. The
      surgical strategy included stent removal and carotid thromboendarterectomy. CASE
      3: Cardiac multiple embolisms in a patient with chronic atrial fibrillation
      caused concomitant leg ischemia and acute carotid stent occlusion 2 hours after
      CAS. Cerebral reperfusion was established by embolectomy, without removing the
      stent. At the same time, the right leg ischemia was resolved by a
      thromboembolectomy with a Fogarty catheter. These three cases demonstrate that
      acute thrombosis after carotid stenting can be managed successfully with emergent
      surgical intervention. Thromboendarterectomy with stent removal or in selected
      cases, simple thromboembolectomy, can minimize neurologic sequelae in patients
      suffering from acute post-stenting carotid thrombosis.

PMID- 16275460
TI  - Repair of juxtarenal para-anastomotic aortic aneurysms after previous open repair
      with fenestrated and branched endovascular stent grafts.
AB  - Three patients with juxtarenal para-anastomotic aortic aneurysms after previous
      open abdominal aortic aneurysm repair were treated with custom-designed
      fenestrated and branched Zenith endovascular stent grafts. Six renal arteries and
      two superior mesenteric arteries were targeted for incorporation by graft
      fenestrations and branches. The fenestration/renal ostium interface was secured
      with balloon-expandable Genesis stents (n = 5) or Jostent stent grafts (n = 1).
      Completion angiography demonstrated no endoleaks and antegrade perfusion in all
      target vessels. During follow-up, one patient developed asymptomatic renal artery
      occlusion and underwent further endovascular intervention for type I distal
      endoleak. Computed tomography at 12 months demonstrated complete aneurysm
      exclusion in all patients with antegrade perfusion in the remaining target
      vessels. Fenestrated and branched endovascular stent grafts may be an acceptable
      alternative to conventional open repair in this group of patients.

PMID- 16275461
TI  - Detection of endograft fractures with multidetector row computed tomography.
AB  - Delayed endograft metallic strut failures detected in vivo with multidetector row
      computed tomography (MDCT) are reported in two patients who underwent
      endovascular abdominal aortic aneurysm repair with AneuRx and Talent endografts.
      In both instances, nitinol fractures were associated with proximal migration and
      type I endoleak. In both cases, the metallic strut fractures were detected with
      transverse sections from 16-channel MDCT angiograms and confirmed by using volume
      rendering. These cases highlight the previously unreported ability of thin
      section, high-resolution MDCT angiography to detect endograft strut fractures.

PMID- 16275462
TI  - Endovascular repair of an actively hemorrhaging gunshot injury to the abdominal
      aorta.
AB  - Endovascular stents have had a limited role in the management of trauma and
      vascular emergencies involving active hemorrhage. We describe a patient with
      delayed rupture of the infrarenal aorta after intra-abdominal sepsis caused the
      breakdown of a primary aortic repair. A stent-graft repair was performed, as
      concomitant injuries did not allow anterior access to the aorta. This report
      describes the successful endovascular repair of an actively hemorrhaging
      penetrating abdominal aortic injury. Endovascular approaches to aortic injuries
      may be valuable in settings where a hostile abdomen precludes traditional open
      repair.

PMID- 16275463
TI  - Successful treatment of a tuberculous vertebral osteomyelitis eroding the
      thoracoabdominal aorta: a case report.
AB  - Mycotic aortic aneurysms are rare complications of systemic tuberculosis that
      affect very few patients. We report a case of a false aneurysm of the visceral
      segment of the aorta that was associated with tuberculous vertebral
      osteomyelitis. Both conditions were successfully treated with antituberculous
      chemotherapy and a combined surgical procedure, ie, aneurysm resection and
      homograft implantation, followed by orthopedic stabilization of the spine.

PMID- 16275464
TI  - Arterial thrombosis associated with heterozygous factor V Leiden disorder,
      hyperhomocysteinemia, and peripheral arterial disease: importance of synergistic
      factors.
AB  - A 47-year-old man with heterozygous factor V Leiden disorder and intermittent
      hyperhomocysteinemia developed spontaneous acute popliteal artery thrombosis.
      Homocysteine levels were above normal limits at presentation. Intra-arterial
      thrombolysis was used successfully to treat the acute thrombosis; long-term
      treatment included anticoagulation, folic acid, and risk factor modification.
      Although factor V Leiden is strongly associated with deep venous thrombosis,
      additional cofactors such as hyperhomocysteinemia may predispose to an increased
      risk of acute arterial thrombosis in areas of pre-existing peripheral arterial
      disease.

PMID- 16275465
TI  - Giant cell arteritis manifesting as mesenteric ischemia.
AB  - We report a case of giant cell arteritis in an 80-year-old woman who presented
      with chronic mesenteric ischemia to our vascular surgery service. Computed
      tomography, arteriography, and magnetic resonance angiography revealed long,
      smooth stenosis of the superior mesenteric artery and focal stenosis of the
      celiac artery. After the patient was found to have an elevated erythrocyte
      sedimentation rate and a positive temporal artery biopsy specimen, glucocorticoid
      therapy was initiated. Giant cell arteritis is a rare and easily overlooked cause
      of vascular insufficiency that can result in a devastating clinical outcome if
      not recognized before surgical therapy or other interventions are attempted.

PMID- 16275466
TI  - Lemierre's syndrome: a potentially fatal complication that may require vascular
      surgical intervention.
AB  - Septic phlebitis of the internal jugular vein, Lemierre's syndrome, is extremely
      rare. However, Lemierre's syndrome may cause septic pulmonary emboli or result in
      fatal systemic sepsis, or both, if a timely diagnosis and appropriate treatment
      are not provided. We present a case of Lemierre's syndrome that occurred in an
      otherwise healthy young man. In this case, progression to a moribund state was
      rapid, and surgical intervention proved lifesaving.

PMID- 16275467
TI  - Chronic mesenteric ischemia: treatment of recurrent disease.

PMID- 16275468
TI  - Bedside placement of inferior vena cava filters by using transabdominal duplex
      ultrasonography and intravascular ultrasound imaging.
AB  - Bedside placement of inferior vena cava filters by using either transabdominal
      duplex ultrasonography or intravascular ultrasonography (IVUS) has been shown to
      be safe and effective. We review techniques for bedside filter placement with
      transabdominal duplex ultrasonography, IVUS with dual venous access, and IVUS
      with single venous access. Transabdominal duplex ultrasonography and IVUS remain
      our preferred techniques for filter placement when feasible, especially in
      critically ill and immobilized patients.

PMID- 16275469
TI  - The ethics of operating on a family member.

PMID- 16275470
TI  - Regarding "Cutting balloon angioplasty of renal fibromuscular dysplasia: a word
      of caution".

PMID- 16275472
TI  - Regarding: "Endovascular treatment of popliteal artery aneurysms: results of a
      prospective cohort study".

PMID- 16275474
TI  - Regarding "Axillobifemoral bypass and aortic embolization for the treatment of
      two patients with ruptured infrarenal aortic aneurysms": complete thrombosis of
      aneurysm prevents rupture?

PMID- 16275476
TI  - We reside in the sun's atmosphere.
AB  - The Sun is the origin of all activities of the Earth, including its solid, liquid
      and gas states, as well as life on the Earth surface. Life was created on this
      planet and was further evolved after long physical/chemical processes, so that
      life here matches with what this planet requires. This paper contends that the
      Earth is located within the solar atmosphere, but we do not feel it in a daily
      life because of the blocking effects of the Earth's magnetic field and
      atmosphere, preventing the entry of the solar atmosphere directly into the
      Earth's domain. This paper emphasizes that we should not attempt to change the
      quality of the natural environment that delicate interactions between the Sun and
      the Earth have established for us by taking a long time.

PMID- 16275477
TI  - Does Schumann resonance affect our blood pressure?
AB  - OBJECTIVES: To investigate whether Schumann resonance (SR) affects blood pressure
      (BP), heart rate (HR), and depression and, if so, whether the putative BP
      reactivity to SR (BPR-SR) is associated with health-related lifestyle (HLS),
      disease-related illnesses (DRI), and depression. METHODS: A sample of 56 adults
      in Urausu, Hokkaido, Japan, wore an ambulatory BP monitor, except for the time in
      the shower, for seven consecutive days. They completed the Geriatric Depression
      Scale-Short Form and a health survey questionnaire on HLS and DRI. Group mean
      differences and within-individual differences in systolic (S) and diastolic (D)
      BP, mean arterial pressure (MAP), double product (DP), and HR were, respectively,
      compared between normal and enhanced SR days, using Student's t-test.
      Correlations between BPR-SR and other characteristics (i.e. age, gender, HLS,
      DRI, subjective health, and depression) were analyzed, using Pearson's product
      moment correlation. RESULTS AND DISCUSSION: Group mean SBP, DBP, MAP, and DP for
      enhanced SR days were lower than those for normal days (P=0.005-0.036). DRI was
      negatively associated with BPR-SR in SBP, DBP, MAP, and DP (P=0.003-0.024),
      suggesting a better health status for those who showed lower BP on enhanced SR
      days. HLS was negatively associated with BPR-SR in DBP and MAP (P=0.016-0.029).
      Males showed higher BPR-SR in DBP and MAP than females (P=0.004-0.016). Neither
      subjective health nor depression was significantly associated with BPR-SR. Future
      studies based on larger sample sizes are planned to see whether possible health
      effects can be generalized.

PMID- 16275478
TI  - Chronomics of autism and suicide.
AB  - We examine whether autism may be influenced by non-photic environmental factors,
      among others, in a California database consisting of the number of cases added
      quarterly to the system between 1993 and 2004. Instead of a precise calendar
      (1.0)-year-long spectral component, we detect unseen primarily helio- and
      geomagnetic signatures, including a newly discovered near-transyear of 1.09-year
      length. In this case, it overrides any undetected seasonal effects, the topic of
      much previous unrewarding research, also analyzed herein without overcoming the
      limitation by stacking. Since we could not get additional data on autism, data on
      suicides, the final "detachment" and failure to bond, were also analyzed, again
      revealing a spectrum of non-photic signatures. What we do not see and do not
      anticipate can exist and can override the seasons, as resolved time
      microscopically by chronomics, the study of chronomes (time structures). Just as
      spatial microscopy and electron microscopy resolved infectious agents, so does
      microscopy in time resolve the signature of environmental agents in human
      behavior in health and disease.

PMID- 16275479
TI  - Circadian and extracircadian exploration during daytime hours of circulating
      corticosterone and other endocrine chronomes.
AB  - During 7 consecutive days, blood and several tissues were collected during
      daytime working hours only, three times per day at 4-h intervals from inbred
      Wistar rats, which had been previously standardized for 1 month in two rooms on a
      regimen of 12 h of light (L) alternating with 12 h of darkness (LD12:12). In one
      room, lights were on from 09:00 to 21:00 and in the other room, lights were on
      from 21:00 to 09:00 (DL12:12; reversed lighting regimen). This setup provides a
      convenient design to study circadian and extracircadian variations over long
      (e.g., 7-day) spans. Prior checking of certain circadian rhythms in animals
      reared in the room on reversed lighting (DL) as compared with animals in the
      usual (LD) regimen provided evidence that the 180 degrees phase-shift had
      occurred. These measurements were limited to the circadian (and not extended to
      infradian) variation. As marker rhythm, the core temperature of a subsample of
      rats was measured every 4 h around the clock (by night as well as by day) before
      the start of the 7-day sampling. An antiphase of the circadian rhythm in core
      temperature was thus demonstrated between rats in the LD vs. DL rooms. A sex
      difference in core temperature was also found in each room. A reversed rhythm in
      animals kept in DL and an antiphase between rats kept in DL vs. LD was again
      shown for the circulating corticosterone rhythm documented in subsamples of 8
      animals of each sex sampled around the clock during the first approximately 1.5
      day of the 7-day sampling. The findings were in keeping with the proposition that
      sampling rats at three timepoints 4 h apart during daytime from two rooms on
      opposite lighting regimens allows the assessment of circadian changes, the
      daytime samples from animals kept on the reversed lighting regimen accounting for
      the samples that would have to be obtained by night from animals kept in the room
      with the usual lighting regimen. During the 7-day-long follow-up, circadian and
      extracircadian spectral components were mapped for serum corticosterone, taking
      into account the large day-to-day variability. A third check on the
      synchronization of the animals to their respective lighting regimen was a
      comparison (and a good agreement) between studies carried out earlier on the same
      variables and the circadian results obtained on core temperature and serum
      corticosterone in this study as a whole. The present study happened to start on
      the day of the second extremum of a moderate double magnetic storm. The study of
      any associations of corticosterone with the storm is beyond our scope herein, as
      are the results on circulating prolactin, characterized by a greater variability
      and a larger sex difference than corticosterone. Sex differences and
      extracircadian aspects of prolactin and endothelin determined in the same samples
      are reported elsewhere, as are results on melatonin. Prior studies on melatonin
      were confirmed insofar as a circadian profile is concerned by sampling on two
      antiphasic lighting regimens, as also reported elsewhere. Accordingly, a
      circadian map for the rat will eventually be extended by the result of this study
      and aligned with other maps with the qualification of the unassessed contribution
      in this study of a magnetic storm.

PMID- 16275480
TI  - Yearly and perhaps transyearly human natality patterns near the equator and at
      higher latitudes.
AB  - Data on the daily numbers of births in Davao, Philippines, available from 1993 to
      2003 are re-analyzed herein by linear-nonlinear rhythmometry, as are data from
      Italy and Japan. A transyear, characterizing the solar wind and other non-photic
      physical environmental factors, corresponds to a spectral peak of the near
      equatorial natality series. This component with a period of about 1.3 years is
      found to have an amplitude larger than the calendar year, the amplitude ratio
      being 134%. Whereas the transyear is validated nonlinearly, the 95% confidence
      interval for the period extending from 1.21 to 1.38 years and the 95% confidence
      interval for the amplitude not overlapping zero (P < 0.05), the annual variation
      is only demonstrable by linear least squares analysis. The results bring added
      evidence for an influence of non-photic environmental effects on human
      physiology, in this case data collected near the equatorial region, Davao being
      situated at 7 degrees N, 126 degrees E. They are in keeping with some degree of
      generality of a rule of reciprocity among mutually supporting physical and
      biological periodicities. They do not detract from the fact that in other longer
      data sets at higher latitudes, the calendar year, presumably reflecting climatic
      influences, dominates the spectrum.

PMID- 16275481
TI  - India revisited: a new hospital and center culminating multidecadal cooperation.
      From cancer chronoradiotherapy to routine cardiovascular chronotheranostics and
      further joint Indian-US and international BIOCOS research.

PMID- 16275482
TI  - An attempt to integrate Western and Chinese medicine: rationale for applying
      Chinese medicine as chronotherapy against cancer.
AB  - Current Western medical treatment lays its main emphasis on evidence-based
      medicine (EBM) and cure is assessed by quantifying the effects of treatment
      statistically. In contrast, in Chinese medicine, cure is generally assessed by
      evaluating the patient's "pattern" (Zheng) [cf. Glossary] and medicines are
      prescribed according to this. We believe that traditional Chinese medicine (TCM)
      cannot be evaluated precisely according to Western principles, in which a
      constant amount of the same medicine is given to a group of patients to be
      evaluated. When assessing cure using TCM, Zheng is more important than the
      determination of medical effects. This means that quantitative evaluation of TCM
      treatment can be very difficult. In this paper, we focused on the Yin-Yang [cf.
      Glossary]balance to determine Zheng, and at the same time attempted to determine
      the treatment effects by applying the concept of regulation of Yin-Yang according
      to chronotherapeutic principles. According to Zheng, advanced cancer patients
      generally lack both Yin and Yang. Chinese medical treatment therefore seeks to
      supplement both Yin and Yang. However, we divided patients into two groups and
      compared them with respect to survival. One group was administered a
      predominantly Yang (Qi) [cf. Glossary] tonic herbal treatment during the daytime,
      while the other group was administered Yin (Blood) [cf. Glossary] tonics during
      night time. A comparison of the results of treatment showed that the patients in
      the group receiving Yang (Qi) replenishment during the daytime lived longer than
      patients receiving Yin (Blood) nourishment during the night. Moreover, the
      patients in the daytime Yang (Qi) replenishment group also fared significantly
      better than patients treated solely by Western methods.

PMID- 16275484
TI  - Man-made electromagnetic noises causing difficulty in geomagnetic and geoelectric
      observations in city area.
AB  - In city area, there are several types of electromagnetic noises originated in
      daily activities of human beings. The noises possibly cause difficulty to detect
      geomagnetic and geoelectric signatures. It is important for investigators who are
      studying geomagnetic effects for biology, medicine and so on to be aware that
      such noises are present in city area. Among these noises, the one due to electric
      railways driven by direct-current electric power supply might give the largest
      influence because this type of noise continues almost all the time and have
      complex wave forms. The characteristics of the noises are briefly introduced by
      showing a theoretical background and some experimental studies.

PMID- 16275483
TI  - Why continued surveillance? Intermittent blood pressure and heart rate
      abnormality under treatment.
AB  - Several opinion leaders have monitored their blood pressure systematically a
      sufficient number of times a day for chronomic (time structural) analyses, from
      the time of encountering chronobiology until their death; they set an example for
      others who also may not wish to base treatment on single spotchecks in a health
      care office. Such self-measurements, while extremely helpful, were not readily
      feasible without a noteworthy interruption of activities during waking as well as
      of sleep. New, relatively unobtrusive instrumentation now makes monitoring
      possible and cost-effective and will save lives. Illustrative results and
      problems encountered in an as-one-goes self-survey by GSK, a physician-scientist,
      are presented herein. Both MESOR-hypertension and CHAT (circadian hyper-amplitude
      tension) can be intermittent conditions even under treatment, and treatment is
      best adjusted based on monitoring, rather than "flying blind".

PMID- 16275485
TI  - Opportunity of detecting pre-hypertension: worldwide data on blood pressure
      overswinging.
AB  - Overswinging or CHAT (brief for Circadian Hyper-Amplitude-Tension), that is an
      excessive circadian variation in blood pressure (BP), has been associated with a
      large increase in cardiovascular disease risk, present even in the absence of an
      elevated BP itself. This usually asymptomatic condition is usually overlooked by
      current practice based on spot-checks, because to be diagnosed, measurements need
      to be taken around-the-clock, preferably for 7 days at the outset. Once
      diagnosed, however, a usual circadian BP pattern can be restored by means of
      certain non-pharmacologic or pharmacologic interventions timed appropriately.
      Thereby, it is possible to reduce the risk of cardiovascular morbidity and
      mortality, cerebral ischemic events and nephropathy in particular. For the
      preparation of guidelines regarding the diagnosis of BP disorders and for the
      institution of primary as well as secondary preventive measures, it is important
      to know what the incidence of CHAT is on a global basis. We found 191 cases of
      CHAT among 1602 mostly 7-day/24-h BP profiles, obtained from several centers in
      different countries participating in an ongoing project on the BIOsphere and the
      COSmos (BIOCOS). CHAT incidence is about the same between men and women, but it
      is diagnosed more often among patients with borderline hypertension or with
      glucose intolerance. It is also more common among MESOR-hypertensive than among
      MESOR-normotensive individuals. Priority should be given to the development of an
      unobtrusive and affordable device to automatically monitor BP and to analyze the
      data as-one-goes, so that cardiovascular disease risk can be prevented.

PMID- 16275486
TI  - Effect of betaxolol hydrochloride on heart rate variability indices during
      exercise stress testing in patients with hypertension.
AB  - Betaxolol hydrochloride is a beta1-selective antagonist that produces
      vasodilation in patients with hypertension and ischemic heart disease. The goal
      of the present study was to characterize the effect of betaxolol on heart rate
      variability indices (HRV), a well-established prognostic marker. Symptom limited
      treadmill exercise testing was performed in 17 hypertensive patients (60.9 +/-
      14.8 years-old) before and immediately a 3 weeks course of betaxolol
      hydrochloride (5 mg daily). Frequency domain HRV (high frequency spectra, HF;
      0.15-0.40 Hz: low frequency spectra, LF; 0.04-0.15 Hz) was measured during
      exercise treadmill testing using MemCalc software. Betaxolol hydrochloride
      significantly decreased the maximal systolic blood pressure and heart rate (184
      +/- 29 vs. 156 +/- 26 mmHg, P < 0.01; 132 +/- 21 vs. 113 +/- 15 bpm, P < 0.01)
      and significantly increased HF and LF during exercise treadmill testing (HF, 32
      +/- 36 vs. 56 +/- 55 men/Hz, P < 0.01; LF, 64 +/- 58 vs. 95 +/- 86 men/Hz, P <
      0.01). Thus, treatment with betaxolol hydrochloride resulted in a decrease in
      blood pressure during exercise treadmill testing and in an increase in HRV. This
      suggests that this agent could have beneficial effects on long-term prognosis in
      patients with hypertension.

PMID- 16275487
TI  - Recombinant interferon alpha treatment decreases heart rate variability indices
      and impairs exercise tolerance in patients with chronic hepatitis.
AB  - Complications of interferon (IFN) therapy include cardiac arrhythmias, impaired
      cardiac function and myocardial ischemia. Decreased heart rate variability (HRV)
      indices, impaired exercise tolerance and decreased left ventricular (LV) function
      are related to unfavorable outcome of heart disease. To investigate the effect of
      IFN therapy on HRV, exercise tolerance and cardiac function, 24-h ambulatory
      electrocardiographic monitoring (AECG), two-dimensional echocardiography, and
      exercise treadmill testing (ETT) was performed in 9 patients (age 56 +/- 9 years
      old) with chronic hepatitis and without underlying heart disease before and after
      treatment with IFN (recombinant alpha 2b; 10 x 10(6) U/day for 4 weeks). HRV
      parameters consisted of standard deviation of RR interval (sdNN, ms), SDANN (ms),
      S.D. index (ms), rMSSD (ms), pNN50 (%) and frequency analysis of heart rate
      spectrum resulted in low (ms, 0.04-0.15 Hz), high (ms, 0.15-0.40 Hz) and total
      (ms, 0.01-1.00 Hz) frequency components. Ischemia was not detected by AECG or
      ETT, and LV function was normal after INF treatment in all patients. However, INF
      treatment resulted in a decrease in exercise tolerance time (449 +/- 94 s vs. 329
      +/- 67 s, P < 0.05) and a decrease in several HRV parameters (S.D. index, 42 +/-
      5 ms vs. 37 +/- 9 ms; rMSSD, 22 +/- 5 ms vs. 19 +/- 4 ms; pNN50, 4 +/- 3% vs. 2
      +/- 1%; P < 0.05). Further, patients treated with INF tended to have a lower sdNN
      and total frequency spectra, although this difference did not reach the level of
      statistical significance. These data suggest that the arrhythmogenic effect of
      INF may be mediated by decreases in HRV and impairment of exercise tolerance even
      in patients without overt heart diseases. Further, INF therapy may be
      contraindicated in patients with predisposing severe cardiac disorders, including
      arrhythmias, ischemia and decreased LV function.

PMID- 16275488
TI  - Effect of antiarrhythmic agents on heart rate variability indices after
      myocardial infarction: comparative experimental study of aprindine and
      procainamide.
AB  - The cardiac arrhythmic suppression trial (CAST) reported that antiarrhythmic
      treatments in post-myocardial infarction (MI) patients resulted in poor outcome
      and decreased in heart rate variability indices (HRV). The goal of the present
      study was to determine whether aprindine and procainamide, antiarrhythmic agents
      that increase HRV, result in beneficial effects in post-MI rabbits. Four weeks
      before experiment, MI was induced in four rabbits by ligating the major branch of
      left coronary artery. A total of eight rabbits (four post-MI and four normal
      rabbits) were randomly assigned to treatment with either intravenous aprindine (1
      mg/kg) or intravenous procainamide (15 mg/kg). Frequency domain HRV (low
      frequency spectra, LF, 0.04-0.15 Hz; high frequency spectra, HF, 0.15-0.40 Hz)
      were assessed by MemCalc software. Aprindine significantly increased HF and LF in
      both MI and normal rabbits, whereas procainamide tended to decrease HF and LF in
      MI and normal rabbits (in total rabbits; aprindine, LF, from 6.3 +/- 7.9 to 16.5
      +/- 15.0 ms(2)/Hz, P < 0.05; HF, from 8.0 +/- 11.7 to 17.5 +/- 15.0 ms(2)/Hz, P <
      0.05; procainamide, LF, from 4.9 +/- 7.4 to 4.8 +/- 8.5 ms(2)/Hz, NS; HF, from
      11.1 +/- 23.0 to 5.1 +/- 10.6 ms(2)/Hz, NS). Under pharmacological denervation
      with propranolol (0.1 mg/kg) and atropine (0.04 mg/kg), aprindine increased LF
      and HF (LF, from 0.2 +/- 0.2 to 0.8 +/- 0.7 ms(2)/Hz, P < 0.05; HF, from 0.1 +/-
      0.0 to 0.2 +/- 0.0 ms(2)/Hz, P < 0.05). These data suggest that aprindine can
      increase HRV in post-MI rabbits. Further experiments in human subjects would be
      of benefit.

PMID- 16275489
TI  - Effect of the alternative magnetic stimulation on peripheral circulation for
      regenerative medicine.
AB  - Regenerative medicine for patients with peripheral atherosclerosis attracts
      considerable attention around the world. However, ethical problems persist in
      gene therapy. This study evaluates the effect of alterative magnetic stimulation
      on peripheral circulation. The effect of magnetic stimulation as a medical
      treatment was examined using a thermograph for 11 healthy volunteers. The
      thermograph was used to measure the rise in skin temperature. The experimental
      results suggested an improvement in the peripheral circulation. The results of
      our study suggest the effectiveness of alternative magnetic stimulation on
      atherosclerosis. We intend to extend our study in order to establish a
      methodology for regenerative medical treatment for patients with peripheral
      atherosclerosis. Further, we wish to advance the current research in the field of
      angiogenesis.

PMID- 16275490
TI  - Cardio-ankle vascular index (CAVI) for the monitoring of the atherosclerosis
      after heart transplantation.
AB  - Atherosclerosis has been reported to progress rapidly after heart
      transplantation. A quantitative diagnosis is required for the diagnosis of
      atherosclerosis after heart transplantation. In this study, we compared brachial
      ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) for the
      diagnosis. The average values of both baPWV and CAVI in the seven cases after
      heart transplantation were found to be signif-icantly large in comparison to the
      average values of the normal healthy people of the same age group. When
      comparisons were made before and after the heart transplantation in a particular
      case, CAVI was stable and baPWV changed sharply. A lot of parameters such as
      blood pressure, blood volume, etc. have been reported to influence baPWV. The
      results of this study suggested that CAVI was a stable parameter in comparison to
      baPWV even after heart transplantation. Thus, CAVI may be useful in the diagnosis
      of arteriosclerosis after heart transplantation.

PMID- 16275492
TI  - A novel apparatus for non-contact measurement of heart rate variability: a system
      to prevent secondary exposure of medical personnel to toxic materials under
      biochemical hazard conditions, in monitoring sepsis or in predicting multiple
      organ dysfunction syndrome.
AB  - BACKGROUND: The impaired balance of the low-frequency/high-frequency ratio
      obtained from spectral components of RR intervals can be a diagnostic test for
      sepsis. In addition, it is known that a reduction of heart rate variability (HRV)
      is useful in identifying septic patients at risk of the development of multiple
      organ dysfunction syndrome (MODS). We have reported a non-contact method using a
      microwave radar to monitor the heart and respiratory rates of a healthy person
      placed inside an isolator or of experimental animals exposed to toxic materials.
      APPARATUS DESIGN AND TESTING: With the purpose of preventing secondary exposure
      of medical personnel to toxic materials under biochemical hazard conditions, we
      designed a novel apparatus for non-contact measurement of HRV using a 1215 MHz
      microwave radar, a high-pass filter, and a personal computer. The microwave radar
      monitors only the small reflected waves from the subject's chest wall, which are
      modulated by the cardiac and respiratory motion. The high-pass filter enhances
      the cardiac signal and attenuates the respiratory signal. In a human trial, RR
      intervals derived from the non-contact apparatus significantly correlated with
      those derived from ECG (r=0.98, P<0.0001). The non-contact apparatus showed a
      similar power spectrum of RR intervals to that of ECG. CONCLUSIONS: Our non
      contact HRV measurement apparatus appears promising for future pre-hospital
      monitoring of septic patients or for predicting MODS patients, inside isolators
      or in the field for mass casualties under biochemical hazard circumstances.

PMID- 16275491
TI  - Plasma catecholamines: follow-up on 10-year study in health and cardiovascular
      disease.
AB  - The predictive value of blood pressure (BP), heart rate (HR), and catecholamines
      in terms of any subsequent development of cardiovascular disease was
      investigated. Systolic (S) and diastolic (D) BP, HR, epinephrine (E) and
      norepinephrine (NE) were measured three times a year in 1980, 1984, and 1989 on
      20 clinically healthy subjects, 18 patients with 'essential hypertension', and 22
      patients with angina pectoris. Of the 22 patients in the latter group, 15 died
      during a 2-year follow-up (1990-1991). Each individual data series was analyzed
      by single cosinor to assess the circannual variation. Results were summarized by
      population-mean cosinor for each group. Parameter tests were used to compare the
      circannual rhythm characteristics among the different patient groups. A
      circannual rhythm was invariably demonstrated on a group basis (P < 0.05).
      Differences in MESOR and/or circannual amplitude were found among the different
      groups. In particular, patients with angina pectoris who will die within the 2
      year follow-up differ in terms of their E and NE from all other patient groups, a
      difference already detected at the beginning of the study, more than 10 years
      before they die. A similar separation is not achieved in terms of BP or HR.

PMID- 16275493
TI  - Prokaryotic and eukaryotic unicellular chronomics.
AB  - An impeccable time series, published in 1930, consisting of hourly observations
      on colony advance in a fluid culture of E. coli, was analyzed by a periodogram
      and power spectrum in 1961. While the original senior author had emphasized
      specifically periodicity with no estimate of period length, he welcomed further
      analyses. After consulting his technician, he knew of no environmental
      periodicity related to human schedules other than an hourly photography. A
      periodogram analysis in 1961 showed a 20.75-h period. It was emphasized that "...
      the circadian period disclosed is not of exactly 24-h length." Confirmations
      notwithstanding, a committee ruled out microbial circadian rhythms based on
      grounds that could have led to a different conclusion, namely first, the
      inability of some committee members to see (presumably by eyeballing) the rhythms
      in their own data, and second, what hardly follows, that there were "too many
      analyses" in the published papers. Our point in dealing with microbes and humans
      is that analyses are indispensable for quantification and for discovering a
      biologically novel spectrum of cyclicities, matching physical ones. The scope of
      circadian organization estimated in 1961 has become broader, including about 7
      day, about half-yearly, about-yearly and ex-yearly and decadal periodisms, among
      others. Microbial circadians have become a field of their own with eyeballing,
      yet time-microscopy can quantify characteristics with their uncertainties and can
      assess broad chronomes (time structures) with features beyond circadians. As yet
      only suggestive differences between eukaryotes and prokaryotes further broaden
      the perspective and may lead to life's sites of origin and to new temporal
      aspects of life's development as a chronomic tree by eventual rhythm dating in
      ontogeny and phylogeny.

PMID- 16275495
TI  - Short and long term analysis of heart rate variations in spontaneously
      hypertensive rats: effects of DSP-4 administration.
AB  - The purpose of this study was to investigate whether or not central noradrenergic
      neurons were involved in the time structure of circadian variation of heart rate
      (HR) in hypertension. We used spontaneously hypertensive rats (SHR(Izm)) and
      normotensive controls (Wistar Kyoto rats, WKY(Izm)). We selectively destroyed the
      noradrenergic neurons in the central nervous system (CNS) by administering
      noradrenergic neurotoxin, N-(2-chloroethy)-N-ethyl-2-bromobenzylamine (DSP4).
      Frequency domain measures of variation of HR (VHR) were obtained using the
      maximum entropy method. The 24-h time frame in VHR is usually dominant in both
      SHR(Izm) and WKY(Izm). Fourteen days after the administering of DSP4, the mean 24
      h systolic arterial pressure (SAP) remained higher in SHR(Izm) than in WKY(Izm).
      After chemical lesion, ultradian rhythms (12-, 8-, 6-, and 4-h periods) in VHR
      became more remarkable in both SHR(Izm) and WKY(Izm) than before chemical lesion.
      Before chemical lesion, an inverse relationship existed between frequency and
      power spectral density in VHR, demonstrating 1/f(beta) characteristics. The slope
      of 1/f(beta) in VHR did not differ between SHR(Izm) and WKY(Izm). After the
      chemical lesion it did not also differ from that of each strain in control period
      (before lesion). Therefore, the noradrenergic neurons may not affect the time
      structure of HR in SHR(Izm) and WKY(Izm) for short-term time analysis. However,
      the intact noradrenergic neurons in CNS may be important to keep normal cardiac
      autonomic function in SHR(Izm) for long-term analysis.

PMID- 16275494
TI  - Time microscopy for all kinds of data including circadian clock biology.
AB  - Data showing a rhythm to the naked eye prominently, barely or not at all were
      described as kinds A, B and C, respectively. Here, we document good agreement
      between estimates of maxima and minima with eyeballing and with the addition of
      point and interval estimates of parameters in kind A data. We also construct a
      chart that provides estimates of uncertainties that can be obtained objectively
      while they are more difficult to quantify subjectively; again there is agreement.
      Interval as point estimates of rhythm characteristics and parameter comparisons
      are useful in charting all kinds of data and become indispensable as we proceed
      from kind A to kind C data. Illustrations included herein from molecular biology
      apply equally to all aspects of transdisciplinary science.

PMID- 16275496
TI  - Chronomics reveal and quantify circadian rhythmic melatonin in duodenum of rats.
AB  - A circadian rhythm is documented in duodenal melatonin in rats, peaking 16.8
      hours after light onset. This component is more readily detected after log10
      transformation of the data. It differs between male and female rats, females
      having a larger circadian amplitude and an earlier acrophase. The circadian
      rhythm in duodenal melatonin is also found to lead that of pineal melatonin. The
      results are qualified by the presence at the start of mapping of the second
      extremum of a double magnetic storm.

PMID- 16275497
TI  - Chronomics: circadian lead of extrapineal vs. pineal melatonin rhythms with an
      infradian hypothalamic exploration.
AB  - A circadian rhythm is documented for plasma, pineal, and hypothalamic melatonin
      of male and female rats kept on staggered lighting regimens. Log[_10]
      transformation of the data usually normalizes, when need be, the distribution of
      residuals from the 24-hour cosine curve fits. A tentative circadian acrophase
      chart is presented that shows a lead in circadian acrophase of duodenal over
      pineal melatonin. The use of antiphasic lighting regimens facilitates circadian
      studies that can be carried out for several days, thereby allowing the assessment
      of infradian components such as a circasemiseptan variation in hypothalamic
      melatonin documented herein. The results are qualified by the presence of a
      second extremum of a double magnetic storm at the start of mapping.

PMID- 16275498
TI  - Chronomics affirm extending scope of lead in phase of duodenal vs. pineal
      circadian melatonin rhythms.
AB  - In Gottingen, Germany, circadian variations in melatonin had been determined time
      macroscopically in pineal glands, blood plasma and duodenum of chicken and rats.
      When these data were meta-analyzed, they agreed with the results from an
      independent survey on tissues from rats collected in a laboratory in Pecs,
      Hungary. In the latter study, tissues were analyzed chemically in Bratislava,
      Slovakia, and numerically in Minneapolis, MN, USA, all by single- and multiple
      component cosinor and parameter tests. In rats and chickens, these inferential
      statistical procedures clearly demonstrated a lead in phase of the 24-h cosine
      curves best fitting all of the duodenal vs. those best fitting all of the pineal
      melatonin values in each species in 2 geographic (geomagnetic) locations. The 24
      h cosine curve of circulating melatonin was found to be in an intermediate phase
      position. Mechanisms of the phase differences and the contribution of
      gastrointestinal melatonin to circulating hormone concentrations are discussed.

PMID- 16275499
TI  - Circasemidian rather than circadian variation of circulating osteoprotegerin in
      clinical health.
AB  - Osteoprotegerin (OPG) serves as a soluble decoy receptor for RANKL to inhibit
      osteoclast formation and activity. Hormones such as PTH and glucocorticoids have
      been reported to decrease OPG concentrations, while estrogens, transforming
      growth factor b, related bone morphogenic factor and thrombopoietin reportedly
      enhance the OPG production in the osteoblastic and bone stromal cells. Since bone
      turnover shows a prominent circadian rhythm in laboratory animals and humans,
      with bone resorption increasing at night, we investigated the time structure of
      circulating OPG concentrations in a group of nine healthy subjects (six women and
      three men; in the age range of 26-49 years). Blood samples for OPG determination
      were collected every 4 h for 24 h on the same day, starting at 08:00 in the
      morning. Data were analyzed by inferential statistical procedures, including the
      single and population-mean cosinor. A 12-h component was found to characterize
      serum OPG concentrations (P = 0.038) with peak concentrations around noon and
      midnight. No statistically significant circadian rhythm of OPG concentrations
      could be found by cosinor in our study population. The mean 24-h OPG
      concentration was higher in women than in men (mean +/- S.E.: 3.13 +/- 0.44 vs.
      1.94 +/- 0.26 pmol/l, Student t = 2.325, P = 0.053). Since PTH concentrations
      also exhibit a bimodal pattern along the 24-h scale, PTH may be tested as a
      putative determinant of the observed changes in serum concentrations of
      osteoprotegerin.

PMID- 16275501
TI  - Chaos analysis of electro encephalography and control of seizure attack of
      epilepsy patients.
AB  - In order to evaluate the EEG of patients with epilepsy, chaos analysis was
      performed for the subdural EEG time series data. The chaos attractor was
      reconstructed in the phase space and the correlation dimension. KS entropy
      calculated from the Lyapunov exponents was evaluated. Before the seizure attack,
      the KS entropy showed a lower value when compared with the time series data
      recorded during healthy condition. The results of our study suggest that it is
      possible to predict the seizure attack by the chaos analysis of the EEG signal.
      Further, we aim at developing an automatic control system for predicting a
      seizure attack by the use of local cooling of the focus with Peltier elements.

PMID- 16275500
TI  - Chronomics of circulating plasma lipid peroxides and anti-oxidant enzymes and
      other related molecules in cirrhosis of liver. In the memory of late Shri Chetan
      Singh.
AB  - BACKGROUND: The chronome (from chronos, time, and nomos, rule; time structure) of
      lipid peroxidation and anti-oxidant defense mechanisms may relate to the efficacy
      and management of preventive and curative chronotherapy. PATIENTS AND METHODS:
      Thirty patients with liver cirrhosis, 25-45 years of age, and 60 age-matched
      clinically healthy volunteers were synchronized for 1 week with diurnal activity
      from about 06:00 to about 22:00 and nocturnal rest. Breakfast was around 08:30,
      lunch around 13:30 and dinner around 20:30. Drugs known to affect the free
      radical system were not taken. Blood samples were collected at 6-h intervals for
      24 h under standardized, presumably 24-h synchronized conditions. Determinations
      included plasma lipid peroxides, in the form of malondialdehyde (MDA), blood
      superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and
      glutathione reductase (GR) activities, and serum total protein, albumin, ascorbic
      acid, and uric acid concentrations. RESULTS: A marked circadian variation was
      demonstrated for each variable in each group by population-mean cosinor (P <
      0.01). In addition to anticipated differences in overall mean value (MESOR),
      patients differed from healthy volunteers also in terms of their circadian
      pattern. CONCLUSION: Mapping the broader time structure (chronome) with age and
      multifrequency rhythm characteristics of antioxidants and pro-oxidants is needed
      for exploring their putative role as markers in the treatment and management of
      liver cirrhosis.

PMID- 16275502
TI  - Incidence of sudden cardiac death, myocardial infarction and far- and near
      transyears.
AB  - We analyzed cycles with periods, tau, in the range of 0.8-2.0 years,
      characterizing, mostly during 1999-2003, the incidence of sudden cardiac death
      (SCD), according to the International Classification of Diseases, 10th revision
      (ICD10), code I46.1. In the tau range examined, only yearly components could be
      documented in time series from North Carolina, USA; Tbilisi, Georgia; and Hong
      Kong, in the latter two locations based on relatively short time series. By
      contrast, in Minnesota, USA, we found only a component with a longer than (=
      trans) yearly (transyearly) tau of 1.39 years; the 95% confidence interval (CI)
      of the tau extended from 1.17 to 1.61 years, falling into the category of
      transyears (defined as a tau and a 95% CI between 1.0 and 2.0 years, with the
      limits of the 95% CI of the spectral component's tau overlapping neither of these
      lengths). During the same span from 1999 to 2003 in Arkansas, USA, a component of
      about 1-year in length was present, and in addition, one with a tau of 1.69 year
      with a CI extending from 1.29 to 2.07 years, a far-transyear candidate, far
      transyears being defined as having a tau with a CI between 1.20 and 2.0 year,
      with the CI overlapping neither of these lengths. In the Czech Republic, there
      was also a calendar-yearly tau and one of 1.76 years. In the latter two
      geographic/geomagnetic areas, the about-yearly and the longer cycles' amplitudes
      were of similar prominence. The taus are only candidate transyears; the 95% CIs
      of their taus overlap the 2-year length. When a series on SCD from 1994 to 2003
      from the Czech Republic was analyzed, the 95% CI of the transyear's tau no longer
      overlapped the 2-year length. Transyears were also found in the Czech Republic
      for myocardial infarctions (MI), meeting the original transyear definition in
      both a shorter and a longer series. Moreover, in the 1994-2003 series on MI from
      the Czech Republic, a near-transyear was also found, meeting the definition of a
      period with a 95% CI overlapping neither precisely 1.0 year nor 1.2 years, along
      with a far-transyear, defined as a tau between 1.2 and 2.0 years, again with the
      95% CI covering neither of these lengths. Herein, we discuss near- and far
      transyears more generally in the light of their background in physics and the
      concept of reciprocal cyclicities.

PMID- 16275503
TI  - Chronomics, neuroendocrine feedsidewards and the recording and consulting of
      nowcasts--forecasts of geomagnetics.
AB  - A multi-center four-hourly sampling of many tissues for 7 days (00:00 on April 5
      20:00 to April 11, 2004), on rats standardized for 1 month in two rooms on
      antiphasic lighting regimens happened to start on the day after the second
      extremum of a moderate double magnetic storm gauged by the planetary geomagnetic
      Kp index (which at each extremum reached 6.3 international [arbitrary] units) and
      by an equatorial index Dst falling to -112 and -81 nT, respectively, the latter
      on the first day of the sampling. Neuroendocrine chronomes (specifically
      circadian time structures) differed during magnetically affected and quiet days.
      The circadian melatonin rhythm had a lower MESOR and lower circadian amplitude
      and tended to advance in acrophase, while the MESOR and amplitude of the
      hypothalamic circadian melatonin rhythm were higher during the days with the
      storm. The circadian parameters of circulating corticosterone were more labile
      during the days including the storm than during the last three quiet days.
      Feedsidewards within the pineal-hypothalamic-adrenocortical network constitute a
      mechanism underlying physiological and probably also pathological associations of
      the brain and heart with magnetic storms. Investigators in many fields can gain
      from at least recording calendar dates in any publication so that freely
      available information on geomagnetic, solar and other physical environmental
      activity can be looked up. In planning studies and before starting, one may gain
      from consulting forecasts and the highly reliable nowcasts, respectively.

PMID- 16275504
TI  - Depressive mood is independently related to stroke and cardiovascular events in a
      community.
AB  - By means of a multivariate Cox model, we investigated the predictive value of a
      depressive mood on vascular disease risk in middle-aged community-dwelling
      people. In 224 people (88 men and 136 women; mean age: 56.8 +/- 11.2 years) of U
      town, Hokkaido (latitude: 43.45 degrees N, longitude: 141.85 degrees E), a
      chronoecological health watch was started in April 2001. Consultations were
      repeated every 3 months. Results at the November 30, 2004 follow-up are presented
      herein. 7-day/24-h blood pressure (BP) and heart rate (HR) monitoring started on
      a Thursday, with readings taken at 30-min intervals between 07:00 h and 22:00 h
      and at 60-min intervals between 22:00 h and 07:00 h. Data stored in the memory of
      the monitor (TM-2430-15, A and D company, Japan) were retrieved and analyzed on a
      personal computer with a commercial software for this device. Subjects were asked
      to answer a self-administered questionnaire inquiring about 15 items of a
      depression scale, at the start of study and again after 1-2 years. Subjects with
      a score higher by at least two points at the second versus first screening were
      classified as having a depressive mood. The other subjects served as the control
      group. The mean follow-up time was 1064 days, during which four subjects suffered
      an adverse vascular outcome (myocardial infarction: one man and one woman;
      stroke: two men). Among the variables used in the Cox proportional hazard models,
      a depressive mood, assessed by the Geriatric Depression Scale (GDS), as well as
      the MESOR of diastolic (D) BP (DBP-MESOR) and the circadian amplitude of systolic
      (S) BP (SBP-Amplitude) showed a statistically significant association with the
      occurrence of adverse vascular outcomes. The GDS score during the second but not
      during the first session was statistically significantly associated with the
      adverse vascular outcome. In univariate analyses, the relative risk (RR) of
      developing outcomes was predicted by a three-point increase in the GDS scale (RR
      = 3.088, 95% CI: 1.375-6.935, P = 0.0063). Increases of 5 mmHg in DBP-MESOR and
      of 3 mmHg in SBP-Amplitude were associated with RRs of 2.143 (95% CI: 1.232
      3.727, P = 0.0070) and 0.700 (95% CI: 0.495-0.989, P = 0.0430), respectively. In
      multivariate analyses, when both the second GDS score and the DBP-MESOR were used
      as continuous variables in the same model, GDS remained statistically
      significantly associated with the occurrence of cardiovascular death. After
      adjustment for DBP-MESOR, a three-point increase in GDS score was associated with
      a RR of 2.172 (95% CI: 1.123-4.200). Monday endpoints of the 7-day profile showed
      a statistically significant association with adverse vascular outcomes. A 5 mmHg
      increase in DBP on Monday was associated with a RR of 1.576 (95% CI: 1.011-2.457,
      P = 0.0446). The main result of the present study is that in middle-aged
      community-dwelling people, a depressive mood predicted the occurrence of vascular
      diseases beyond the prediction provided by age, gender, ABP, lifestyle and
      environmental conditions, as assessed by means of a multivariate Cox model. A
      depressive mood, especially enhanced for 1-2 years, was associated with adverse
      vascular outcomes. Results herein suggest the clinical importance of repetitive
      assessments of a depressive mood and the need to take sufficient care of
      depressed subjects. Another result herein is that circadian and circaseptan
      characteristics of BP variability measured 7-day/24-h predicted the occurrence of
      vascular disease beyond the prediction provided by age, gender, depressive mood
      and lifestyle, as assessed by means of a multivariate Cox model. Earlier, we
      showed that the morning surge in BP on Mondays was statistically significantly
      higher compared with other weekdays. Although a direct association between the
      Monday surge in BP and cardiovascular events could not be demonstrated herein, it
      is possible that the BP surge on Monday mornings may also trigger cardiovascular
      events. We have shown that depressive people exhibit a more prominent circaseptan
      variation in SBP, DBP and the double product (DP) compared to non-depressed
      subjects. In view of the strong relation between depression and adverse cardiac
      events, studies should be done to ascertain that depression is properly diagnosed
      and treated. Chronodiagnosis and chronotherapy can reduce an elevated blood
      pressure and improve the altered variability in BP and HR, thus reducing the
      incidence of adverse cardiac events. This recommendation stands at the basis of
      chronomics, focusing on prehabilitation in preference to rehabilitation, as a
      public service offered in several Japanese towns.

PMID- 16275505
TI  - Arterial stiffness independently predicts cardiovascular events in an elderly
      community -- Longitudinal Investigation for the Longevity and Aging in Hokkaido
      County (LILAC) study.
AB  - We investigated the predictive value of arterial stiffness to assess
      cardiovascular risk in elderly community-dwelling people by means of a
      multivariate Cox model. In 298 people older than 75 years (120 men and 178 women,
      average age: 79.6 years), brachial-ankle pulse wave velocity (baPWV) was measured
      between the right arm and ankle in a supine position. The LILAC study started on
      July 25, 2000, consultation was repeated yearly, and the last follow-up ended on
      November 30, 2004. During this follow-up span of 1227 days, there were nine
      cardiovascular deaths, the cause of death being myocardial infarction for two men
      and three women or stroke for two men and two women. In Cox proportional hazard
      models, baPWV as well as age, Mini-Mental State Examination (MMSE), Hasegawa
      Dementia Scale Revised (HDSR) and the low-frequency/high-frequency (LF/HF) ratio
      showed a statistically significant association with the occurrence of
      cardiovascular death. A two-point increase in MMSE and HDSR score significantly
      protected against cardiovascular death, the relative risk (RR) being 0.776 (P =
      0.0369) and 0.753 (P = 0.0029), respectively. The LF/HF ratio also was
      significant (P = 0.025), but the other indices of HRV were not. After adjustment
      for age and HDSR, a 200 cm/s increase in baPWV was associated with a 30.2%
      increase in risk (RR = 1.302, 95% CI: 1.110-1.525), and a 500 cm/s increase in
      baPWV with a 93.3% increase in risk (RR = 1.933, 95% CI: 1.300-2.874, P =
      0.0011), whereas the LF/HF ratio was no longer associated with a statistically
      significant increase in cardiovascular mortality. In elderly community-dwelling
      people, arterial stiffness measured by means of baPWV predicted the occurrence of
      cardiovascular death beyond the prediction provided by age, gender, blood
      pressure and cognitive functions. baPWV should be added to the cardiovascular
      assessment in various clinical settings, including field medical surveys and
      preventive screening. The early detection of risk by chronomics allows the timely
      institution of prophylactic measures, thereby shifting the focus from
      rehabilitation to prehabilitation medicine, as a public service to several
      Japanese towns.

PMID- 16275506
TI  - Fractal analysis of heart rate variability and mortality in elderly community
      dwelling people -- Longitudinal Investigation for the Longevity and Aging in
      Hokkaido County (LILAC) study.
AB  - AIM: Fractal analysis of heart rate (HR) variability (HRV) has been used as a new
      approach to evaluate the risk of mortality in various patient groups. Aim of this
      study is to examine the prognostic power of detrended fluctuation analysis (DFA)
      and traditional time- and frequency-domain analyses of HR dynamics as predictors
      of mortality among elderly people in a community. METHODS: We examined 298 people
      older than 75 years (average age: 79.6 years) and 1-h ambulatory ECG was
      monitored. During the last 10 min, deep respiration (6-s expiration and 4-s
      inspiration) was repeated six times in a supine position. Time-domain and
      frequency-domain measures were determined by the maximum entropy method. Scaling
      exponents of short-term (<11 beats, alpha 1) and longer-term (>11 beats, alpha 2)
      were determined by the DFA method. Six estimates, obtained from 10-min segments,
      were averaged to derive mean values for the entire recording span. These average
      values were denoted Alpha 1 and Alpha 2, estimates obtained during the first 10
      min segment Alpha 1 S and Alpha 2 S, and those during the last 10-min segment
      Alpha 1E and Alpha 2E, respectively. The LILAC study started on July 25, 2000 and
      ended on November 30, 2004. We used Cox regression analysis to calculate relative
      risk (RR) and 95% confidence interval (CI) for all-cause mortality. Significance
      was considered at a value of P < 0.05. RESULTS: Gender, age and Alpha 2E showed a
      statistically significant association with all-cause mortality. In univariate
      analyses, gender was significantly associated with all-cause mortality, being
      associated with a RR of 3.59 (P = 0.00136). Age also significantly predicted all
      cause mortality and a 5-year increase in age was associated with a RR of 1.49 (P
      = 0.01809). The RR of developing all-cause mortality predicted by a 0.2-unit
      increase in Alpha 2E was 0.58 (P = 0.00390). Other indices of fractal analysis of
      HRV did not have predictive value. In multivariate analyses, when both Alpha 2E
      and gender were used as continuous variables in the same model, Alpha 2E remained
      significantly associated with the occurrence of all-cause mortality (P =
      0.02999). After adjustment for both gender and age, a 0.2-unit increase in Alpha
      2E was associated with a RR of 0.61 (95% CI: 0.42-0.90, p = 0.01151). CONCLUSION:
      An intermediate-term fractal-like scaling exponent of RR intervals was a better
      predictor of death than the traditional measures of HR variability in elderly
      community-dwelling people. It is noteworthy that the longer-term (alpha 2) rather
      than the short-term fractal component (alpha 1) showed predictive value for all
      cause mortality, which suggests that an increase in the randomness of
      intermediate-term HR behavior may be a specific marker of neurohumoral and
      sympathetic activation and therefore may also be associated with an increased
      risk of mortality.

PMID- 16275507
TI  - Common carotid intima-media thickness is predictive of all-cause and
      cardiovascular mortality in elderly community-dwelling people: Longitudinal
      Investigation for the Longevity and Aging in Hokkaido County (LILAC) study.
AB  - Several cohort studies have examined the association of carotid intima-media
      thickness (IMT) with the risk of stroke or myocardial infarction in apparently
      healthy persons. We investigated the predictive value of IMT of cardiovascular
      mortality in elderly community-dwelling people, beyond the prediction provided by
      age and MMSE, assessed by means of a multivariate Cox model. Carotid IMT and
      plaque were evaluated bilaterally with ultrasonography in 298 people older than
      75 years (120 men and 178 women, average age: 79.6 years). The LILAC study
      started on July 25, 2000. Consultations were repeated every year. The follow-up
      ended on November 30, 2004. During the mean follow-up span of 1152 days, 30
      subjects (21 men and nine women) died. Nine deaths were attributable to
      cardiovascular causes (myocardial infarction: two men and three women; stroke:
      two men and two women). The age- and MMSE-adjusted relative risk (RR) and 95%
      confidence interval (95% CI) of developing all-cause mortality was assessed. A
      0.3 mm increase in left IMT was associated with a RR of predicted 1.647 (1.075
      2.524), and a similar increase in right IMT with a RR of 3.327 (1.429-7.746). For
      cardiovascular mortality, the corresponding RR values were 2.351 (1.029-5.372)
      and 2.890 (1.059-7.891), respectively. Carotid IMT assessed by ultrasonography is
      positively associated with an increased risk of all-cause and cardiovascular
      death in elderly community-dwelling people.

PMID- 16275508
TI  - Near-transyear in solar magnetism.
AB  - Daily data on solar magnetism, available from May 1975 to April 2002, were
      analyzed by linear-nonlinear rhythmometry, with particular focus on the near
      transyear, slightly longer than the calendar year. The time structure of solar
      magnetism is compared to that of solar activity, gauged by Wolf numbers. An about
      27-day component corresponding to the solar rotation period, is common to both
      variables but differs in harmonic content. About 10-year component characterizes
      solar activity but not solar magnetism. A near-transyear with a period of about
      1.05 years is detected in solar magnetism. In solar activity, a near-transyear is
      also found but its period of about 1.10 years is longer than that characterizing
      solar magnetism, and it may be paired with an about 0.9-year component to
      correspond to an about 10-year modulation in amplitude or phase of an about
      yearly component.

PMID- 16275509
TI  - Effect of aging on blood pressure in Leh, Ladakh, a high-altitude (3524 m)
      community, by comparison with a Japanese town.
AB  - The effect of aging on blood pressure (BP) and heart rate (HR) was investigated
      in a cross-sectional study in the high-altitude community of Leh, Ladakh
      (altitude: 3524 m) and a Japanese community in U town, Hokkaido (altitude: 25 m).
      BP and HR were obtained in a sitting position from 332 subjects 13-81 years of
      age in Ladakh, and from 216 Japanese citizens, 24-79 years of age. Measurements
      were taken after a 2-min rest, using a semi-automated BP device (UA-767 PC, A and
      D Co. LTD, Tokyo). High-altitude people showed higher diastolic BP and HR values
      than lowland people (83.2 vs. 76.9 mmHg and 78.6 vs. 69.2 bpm, P < 0.001), but no
      difference in systolic BP. Highland people also showed a steeper BP increase with
      age than the lowland people (systolic BP: 0.7476 vs. 0.3179 mmHg/year, P <
      0.0005; diastolic BP: 0.3196 vs. 0.0750 mmHg/year, P < 0.001). This
      chronoecologic investigation in Ladakh examined the circulation as a
      physiological system at high-altitude. Our data indicate the need for a more
      comprehensive cardiovascular assessment for a better diagnosis and a more
      fruitful treatment. Longitudinal observations of effects of socio-ecologic
      factors on the cardiovascular system should help prevent strokes and other
      cardiovascular events, especially at high altitude.

PMID- 16275510
TI  - Chronoecological health watch of arterial stiffness and neuro-cardio-pulmonary
      function in elderly community at high altitude (3524 m), compared with Japanese
      town.
AB  - Effects of high altitude on arterial stiffness and neuro-cardio-pulmonary
      function were studied. Blood pressure (BP) and heart rate (HR) were measured in a
      sitting position on resting Ladakhis, living at an altitude of 3250-4647 m (Phey
      village, 3250 m: 17 men and 55 women; Chumathang village, 4193 m: 29 men and 47
      women; Sumdo village, 4540 m: 38 men and 57 women; and Korzok village, 4647 m: 84
      men and 70 women). The neuro-cardio-pulmonary function, including the Kohs block
      design test, the Up and Go, the Functional Reach and the Button tests, was
      examined in 40 elderly subjects (19 men and 21 women, mean age: 74.7 +/- 3.3
      years) in Leh, Ladakh (altitude: 3524 m), for comparison with 324 elderly
      citizens (97 men and 227 women, mean age: 80.7 +/- 4.7 years) of Tosa, Japan
      (altitude: 250 m). Cardio-Ankle Vascular Index (CAVI) was measured as the heart
      ankle pulse wave velocity (PWV) in these subjects using a VaSera CAVI instrument
      (Fukuda Denshi, Tokyo). SpO(2) decreased while Hb and diastolic BP increased with
      increasing altitude. At higher altitude, residents were younger and leaner. Women
      in Leh vs. Tosa had a poorer cognitive function, estimated by the Kohs block
      design test (3.7 +/- 3.6 vs. 16.4 +/- 9.6 points, P < 0.0001) and poorer ADL
      functions (Functional Reach: 13.7 +/- 7.0 cm vs. 25.3 +/- 8.7 cm, P < 0.0001;
      Button test: 22.5 +/- 4.8 vs. 14.8 +/- 5.7 s, P < 0.0001). Time estimation was
      shorter at high altitude (60-s estimation with counting: 41.1% shorter in men and
      23.0% shorter in women). A higher voltage of the QRS complex was observed in the
      ECG of Leh residents, but two times measurement of CAVI showed no statistically
      significant differences between Leh and Tosa (two times of CAVI measures; 9.49
      vs. 10.01 m/s and 9.41 vs. 10.05 m/s, respectively), suggesting that most
      residents succeed to adapt sufficiently to the high-altitude environment.
      However, correlation of CAVI with age shows several cases who show an extreme
      increase in CAVI. Thus, for the prevention of stroke and other adverse
      cardiovascular outcomes, including dementia, CAVI may be very useful, especially
      at high altitude. In conclusion, elderly people living at high altitude have a
      higher risk of cardiovascular disease than low-latitude peers. To determine how
      these indices are associated with maintained cognitive function deserves further
      study by the longitudinal follow-up of these communities in terms of longevity
      and aging in relation to their neuro-cardio-pulmonary function.

PMID- 16275511
TI  - Geographic and extraterrestrial aspects of morbidity and/or mortality patterns
      from myocardial infarction and stroke.
AB  - Two authors (M.K. and M.M.) provided insight into a manuscript submitted by them
      elsewhere for publication and kindly offered for meta-analysis data on the
      monthly incidence from January 1989 up to December 2004, of 6094 cerebral
      infarctions, 414 intracerebral and 277 subarachnoid hemorrhages, cases admitted
      at the Neurological Clinic in Nove Zamky, Slovakia. Spectral components with a
      period exceeding (beyond = trans) the length of the calendar year--transyears-
      reported originally by M.K. and M.M. are here also documented linearly on
      original data without and after detrending by the fit of first- or second-order
      polynomials. For intracerebral and subarachnoidal hemorrhage, the zero-amplitude
      (no-rhythm) assumption is rejected (P < 0.05, not corrected for multiple testing)
      for the transyear but not for a precise 1.0-year trial period. As reported
      earlier by M.K. and M.M., the transyear's amplitude is larger than the calendar
      year's amplitude for all three series of stroke incidence in Slovakia. The
      putative importance of the new findings stems from earlier and new analyses
      revealing other spectral components that are presumed signatures of
      magnetoperiodisms, e.g. about 50- and 7-year components in about five decades of
      diagnostically unqualified, pooled data on stroke in Minnesota. There is,
      however, the danger of relatively small numbers providing artifacts for loosely
      defined transyears. The original cosinor approach by M.K. and M.M., testing
      anticipated periods, had its strength. The observation of a quindecadal component
      in mortality from strokes in Minnesota supports the presence of signatures of
      effects from extraterrestrial space in acute human pathology such as strokes,
      myocardial infarctions and sudden cardiac death. Magnetoperiodic mechanisms
      remain to be investigated further as added strokes accumulate in Nove Zamky and
      greater Slovakia as well as for sudden cardiac death where transyears have been
      documented in the Czech Republic, in Arkansas and particularly in Minnesota, but
      not elsewhere (as yet?). This study is also a plea for worldwide access to
      morbidity, mortality and natality data that constitute a largely unexploited
      treasure, brought to the fore mainly for relatively short-term comparisons of the
      effect of interventions against the fiction of imaginary baselines.

PMID- 16275512
TI  - Circadian and circaseptan (about-weekly) aspects of immigrant Indians' blood
      pressure and heart rate in California, USA.
AB  - Time structurally (chronomically) interpreted half-hourly monitoring of blood
      pressure (BP) and heart rate (HR) for at least 7 days and preferably for 17 days
      is recommended, separately for a diagnosis of BP disorders and when necessary
      again for the same or longer spans for treatment, whenever a positive diagnosis
      of a disorder is made. In this study, 30 clinically healthy subjects underwent 7
      day monitoring and provided a series of findings, including the detection of
      Circadian Hyper-Amplitude-Tension (CHAT), that is blood pressure overswinging,
      which carries a high risk of hard cardiovascular events. The results specifically
      bear upon south-east Asian-Indian immigrants. They show that cardiovascular
      disease risk increases with age, with a positive family history of hypertension
      and/or other cardiovascular diseases and even with the duration of stay in the
      USA. A relation to body mass index is also shown. Such monitoring for
      prehabilitation may eventually reduce the need for rehabilitation.

PMID- 16275513
TI  - Circadian rhythm of maternal blood pressure and fetal growth.
AB  - This study aimed at examining any relation between the circadian variation in
      blood pressure (BP) in human pregnancy and fetal growth. A prospective study
      included 52 pregnant women monitored during the third trimester of pregnancy.
      There were 33 uncomplicated pregnancies with normal fetal growth (Group 1) and 19
      pregnancies complicated by intrauterine growth retardation (IUGR), confirmed at
      birth (Group 2). Ten women (five in each group) had pregnancy-induced
      hypertension. All women were hospitalized and followed a similar daily routine.
      BP was recorded with an automatic wearable device. Measurements were obtained
      every 20 min for 24 +/- 1 h. BP profiles were analyzed by conventional
      statistical methods and by cosinor, involving the least squares fit of cosine
      curves with an anticipated period (24 h) to the data. BP parameters, fetal
      outcome, demographic and obstetric characteristics were compared between the two
      groups. Logistic regression and multivariate analyses were used to assess factors
      putatively associated with fetal outcome. The circadian amplitude of diastolic BP
      was found to be larger in normotensive women with IUGR. As gauged by odds ratios
      (OR), the circadian amplitude of diastolic BP (OR = 1.7, 95% CI: 1.1-2.8; P =
      0.03) and hematocrit (OR = 1.4, 95% CI: 1.0-1.9; P = 0.04) were the only
      variables positively and independently associated with IUGR. In the presence of
      maternal hypertension, the circadian amplitude of systolic BP was negatively
      associated with IUGR (OR = 0.7, 95% CI: 0.5-1.0; P = 0.03). A larger circadian
      variation in diastolic BP, rather than a difference in the mean value of systolic
      or diastolic BP, was found to be statistically significantly associated with
      IUGR. This study adds another condition in which the circadian BP amplitude
      constitutes a harbinger of elevated risk, apart from an association with a
      shortened lifespan in the absence or presence of malignant hypertension and with
      an increased risk of stroke and nephropathy reported earlier.

PMID- 16275514
TI  - The change of hemodynamics and heart rate variability on bathing by the gap of
      water temperature.
AB  - Bathing in Japanese style may carry negative effects as water pressure on the
      chest and thermal stimulus on hemodynamics take place. We have explored the
      influence of bathing in high temperature water on the change of heart rate
      variability (HRV). Fourteen young healthy male adults, ageing in range from 28 to
      42 years old (the average was 35.8 years old) were selected and took a hot water
      bath (38 and 41 degrees C) for 15 min long. Bathing in 38 degrees C water brought
      no significant change in heart rate (HR) and blood pressure (BP), and the HR in
      41 degrees C increased in early stage. In HRV, high frequency (HF) power did not
      have significant change with little increase in early stages of bathing in 38
      degrees C and decreased continuously in 41 degrees C. Low frequency (LF) power
      and very low frequency (VLF) power decreased gradually in later stages of
      bathing, but the degree of decrease was larger in 41 degrees C. In this study,
      data concerning dizziness after bathing at 41 degrees C was obtained (we named it
      as a "dizzy case"). HF and LF trends in this case followed the same pattern in
      comparison with others' average, but the decrease was larger. Additionally, there
      was no increase in the LF/HF at later stage of bathing. It is thought that this
      reflects a decreased in autonomic nerve activity. In normal subjects the VLF
      increased in later stages of 38 and 41 degrees C bathing, but in the dizziness
      experiencing subject, the increase was very significant. It is conceivable that
      this reflected excessive parasympathetic reflex. Except the dizzy case HF
      decreased continuously in later stage of bathing in both 38 and 41 degrees C, but
      VLF slightly increased. Recently there was an express opinion that the VLF
      correlates with the prognosis; therefore the change of VLF in this study is very
      interesting. Based upon the results of this study we propose that the optimum
      period of time for bathing in water 41 degrees C in temperature is 5 min or less,
      and that for water 38 degrees C in temperature is 10 min or less.

PMID- 16275518
TI  - The evaluation of pulmonary hypertension using right ventricular myocardial
      isovolumic relaxation time.
AB  - Right ventricular (RV) blood pool-derived isovolumic relaxation time (IVRT)
      correlates well with systolic pulmonary arterial pressure (PAP). However, because
      of complex parameter derivation, the method is rarely used. The aim of this study
      was to validate the measurement of myocardial velocity imaging-derived RV IVRT
      (IVRT') against invasively measured PAP. Transthoracic echocardiography with
      myocardial velocity imaging and right heart catheterization were performed in 33
      patients with pulmonary hypertension. Blood pool IVRT and myocardial IVRTs for
      the tricuspid valve annulus ring, basal and apical RV free wall segments were
      measured and compared with data from 33 age- and sex-matched control subjects.
      Measured IVRTs were significantly longer in patients with pulmonary hypertension
      than in control subjects. The strongest correlation (R = 0.74, P < .0001) was
      found between systolic PAP and the heart rate-corrected IVRT' derived from the
      basal RV free wall segment. The basal segment IVRT' corrected for heart rate
      correlates well with the invasive PAP measurement and, therefore, can be used to
      predict systolic PAP. It can even be considered as an alternative to tricuspid
      regurgitation-derived PAP systolic when tricuspid regurgitation is nonrecordable.
      A proposed method to derive systolic PAP should be used while screening the
      patients at risk for pulmonary hypertension, monitoring the disease progression
      and the effect of treatment.

PMID- 16275519
TI  - Heart rate effects on strain and strain rate in healthy children.
AB  - Based on myocardial Doppler echocardiography, regional strain (S) and strain rate
      (SR) can be evaluated as regional parameters of ventricular function. The use of
      these techniques in clinical pediatric cardiology remains a challenge. This study
      establishes reference values for S and SR in both systole and diastole in healthy
      children over a large age range and evaluates the potential relationships of
      demographic and echocardiographic parameters on S and SR, and, in particular,
      assesses the clinical effect of heart rate on S and SR in healthy children. It is
      shown that heart rate changes in children during growth have an important impact
      on both systolic and diastolic myocardial S and late diastolic SR. Therefore, to
      evaluate regional myocardial function in children, heart rate at rest should be
      considered an important factor.

PMID- 16275520
TI  - Midwall shortening after coarctation repair: the effect of through-plane motion
      on single-plane indices of left ventricular function.
AB  - Left ventricular midwall function is increased after repair of coarctation of the
      aorta (CoA). The cause is unclear. This study aimed to examine the variance
      between fiber shortening derived from 3-dimensional models of myocardial
      deformation, and 1- and 2-dimensional indices of left ventricular systolic
      function. In all, 15 young adults after CoA and 15 matched control subjects were
      recruited. Endocardial and midwall fractional shortening were calculated using M
      mode echocardiography. Ejection fraction, midwall fractional shortening, and
      myocardial deformation were calculated or measured from magnetic resonance (MR)
      imaging. Echocardiographic and cine-MR imaging midwall fractional shortening were
      increased after CoA (P = .02 and < .001). In contrast, 3-dimensional MR tagging
      demonstrated normal midwall circumferential shortening and decreased longitudinal
      shortening in the CoA group (P < .01). Cine MR midwall shortening, recalculated
      to allow for through-plane motion, was similar to tagged midwall shortening, with
      no difference between the CoA and control groups. After CoA, measures of left
      ventricular function systematically overestimate midwall fiber shortening unless
      the methodology accounts for through-plane motion.

PMID- 16275521
TI  - Echocardiographic assessment of isolated pulmonary valve stenosis: which
      outpatient Doppler gradient has the most clinical validity?
AB  - Maximum instantaneous Doppler gradient has been the primary variable used to
      assess severity of pulmonary valve stenosis. However, recent observations suggest
      that outpatient maximum Doppler gradient often overstates clinical severity, as
      measured by catheter peak-to-peak gradient (PPG). This study sought to determine
      which outpatient Doppler gradient was most predictive of subsequently measured
      PPG. Ninety patients were included. Outpatient mean Doppler gradient showed the
      best correlation and agreement with the catheter PPG (r = 0.82, bias = -5 mm Hg).
      Maximum Doppler gradients, even when corrected for proximal velocity,
      consistently overestimated the PPG (bias = +21-26 mm Hg). Outpatient mean
      gradient was most predictive of subsequent PPG and should be used to determine
      whether to intervene for patients with isolated pulmonary valve stenosis. Use of
      only the maximum Doppler gradient to assess pulmonary valve stenosis will lead to
      a systematic overstatement of the severity of the stenosis.

PMID- 16275522
TI  - Outpatient echocardiographic assessment of complex pulmonary outflow stenosis:
      Doppler mean gradient is superior to the maximum instantaneous gradient.
AB  - Evaluation of pulmonary outflow obstruction has focused on maximum instantaneous
      gradient (MIG). However, experience suggests that outpatient Doppler MIG often
      overstates the degree of stenosis. In this study of 132 patients with complex
      pulmonary stenosis, the mean Doppler gradient showed superior correlation and
      agreement with invasive peak-to-peak gradient (PPG) (r = 0.91, bias = -6 mm Hg).
      Agreement between mean gradient and PPG remained excellent for patients with
      prosthetic conduits (bias = -4 mm Hg). When PPG was 50 mm Hg more, both mean
      Doppler gradient and MIG corrected for prevalve velocity provided reasonable
      estimates of PPG (bias = -13 and +17 mm Hg, respectively). Uncorrected MIG
      remained significantly greater than PPG (bias = +27 mm Hg). Outpatient MIG
      consistently overstated subsequent PPG. In unselected patients with conduits or
      with PPG of 50 mm Hg or less, mean Doppler gradient provided the best prediction
      of PPG. These data provide a strong argument for the routine use of mean
      gradients in complex pulmonary stenosis.

PMID- 16275523
TI  - Tissue Doppler imaging and brain natriuretic peptide levels in adults with
      repaired tetralogy of Fallot.
AB  - BACKGROUND: Accurate estimation of right ventricular (RV) function in patients
      with repaired tetralogy of Fallot (RTOF) is difficult, partly due to the presence
      of tricuspid regurgitation and pulmonary regurgitation and/or stenosis. The aim
      of the present study was to evaluate RV systolic and diastolic function of adult
      asymptomatic patients with RTOF by means of tissue Doppler imaging (TDI) and
      brain natriuretic peptide (BNP) values. METHODS: 25 adult patients with RTOF and
      25 healthy controls were studied. The following echocardiographic measurements
      were obtained: RV diameter/left ventricular (LV) diameter (RVD/LVD) and systolic
      (Sa) and diastolic (Ea, Aa) velocities at the RV free wall tricuspid annulus
      site. Serum BNP levels were measured as well. RESULTS: Patients with RTOF
      demonstrated reduced TDI velocities: Sa, 8.16 +/- 1.15 versus 16.43 +/- 1.15
      cm/sec (P < .001); Ea, 10.00 +/- 2.18 versus 18.99 +/- 1.00 cm/sec (P < .001);
      Aa, 5.64 +/- 1.77 vs. 13.69 +/- 0.86 cm/sec (P < .001). Patients with RTOF also
      had higher BNP levels than controls (85.0 +/- 87.0 vs 5.36 +/- 1.0 pg/mL; P <
      .001). The increased BNP levels in RTOF patients correlated with the RVD/LVD
      ratio (r = .521; P < .01). CONCLUSIONS: Our results indicate that although our
      cohort of patients was asymptomatic, using TDI and BNP allowed us to easily
      discriminate them from the healthy controls. The ability of TDI to assess
      ventricular function even in the presence of valvular lesions, as in RTOF
      patients, makes it a valuable tool in the investigation and follow-up of these
      patients.

PMID- 16275524
TI  - Subvalvular left ventricular outflow obstruction for patients undergoing aortic
      valve replacement for aortic stenosis: echocardiographic recognition and
      identification of patients at risk.
AB  - Persistently high gradients after aortic valve replacement (AVR), potentially
      caused by prosthesis-patient mismatch or superimposed but unrecognized
      nonvalvular obstruction, are associated with adverse clinical outcomes.
      Concomitant valvular and subvalvular left ventricular outflow obstruction was
      first hypothesized in 1957, and identified and further characterized in the
      1960s, before the availability of echocardiography. Although obstruction as a
      result of subvalvular hypertrophy complicating valvular aortic stenosis has been
      subsequently described using echocardiography, it has largely fallen from
      consciousness in the preoperative and intraoperative echocardiographic assessment
      of patients undergoing AVR for aortic stenosis. As such, subvalvular left
      ventricular outflow obstruction complicating valvular aortic stenosis is a
      potentially preventable cause of persistently high gradients that remains
      relatively frequently encountered after AVR. This review is intended to draw
      attention to this phenomenon, to describe its mechanisms, and to provide guidance
      for its preoperative or intraoperative recognition using echocardiographic
      imaging techniques, with the goal that recognition and appropriate intervention
      at the time of AVR will decrease its clinical impact.

PMID- 16275525
TI  - Transthoracic Doppler echocardiographic assessment of coronary flow velocity
      pattern in patient with acute myocardial infarction implies progression of
      myocardial damage.
AB  - BACKGROUND: Coronary flow velocity (CFV) pattern with a rapid deceleration time
      of diastolic flow velocity and small average systolic peak velocity immediately
      after reperfusion implies poor wall-motion recovery in patients with acute
      myocardial infarction. Microvascular injury has been demonstrated to progress
      after coronary reperfusion. The purpose of this study was to assess whether CFV 1
      day after reperfusion (day 1) may reflect accurately the degree of myocardial
      damage. METHODS: In the left anterior descending coronary artery in 29 patients
      with anterior acute myocardial infarction, CFV was measured immediately and 1 day
      after recanalization using transthoracic Doppler echocardiography, respectively.
      Regional wall motion was estimated as anterior wall-motion score index (AWMSI) by
      echocardiography before recanalization and 1 month after the onset of acute
      myocardial infarction. RESULTS: Although significant correlation was observed
      among deceleration time of diastolic flow velocity, average systolic peak
      velocity, and average peak velocity immediately after reperfusion and 1-month
      AWMSI (r = -0.62, P < .001; r = -0.61, P < .001; and r = -0.55, P < .01,
      respectively), much better correlation was demonstrated between those at day 1
      and 1-month AWMSI (r = -0.72, P < .0001; r = -0.68, P < .0001; and r = -0.60, P <
      .001, respectively). Deceleration time of diastolic flow velocity, average
      systolic peak velocity, and average peak velocity in poor wall-motion recovery
      group (1-month AWMSI > 2.0, n = 14) were significantly smaller (P < .01, P < .05,
      and P < .05, respectively) at day 1 compared with those immediately after
      reperfusion. CONCLUSIONS: CFV pattern assessed by transthoracic Doppler
      echocardiography at day 1 provides the degree of myocardial damage much more
      accurately than that immediately after reperfusion. These results may suggest
      that myocardial damage progresses after reperfusion.

PMID- 16275526
TI  - Serial changes in regional diastolic left ventricular function after a first
      acute myocardial infraction.
AB  - After acute myocardial infarction (AMI), regional diastolic function may be
      abnormal even though regional systolic function appears normal. However, it is
      not known whether this represents a transient or permanent phenomenon, and the
      relation to myocardial viability is not known. To determine this we assessed
      regional left ventricular function during contraction and filling after AMI in
      106 patients with a first AMI. Echocardiography with color kinesis was performed
      on day 1 and 1, 3, and 6 months after AMI. For both left ventricular systole and
      diastole the percentage of segments with abnormal wall motion was calculated.
      During the first 6 months, the area of diastolic wall-motion abnormality
      decreased (38 +/- 16%-30 +/- 27%, P = .001) whereas no overall change in area of
      systolic wall-motion abnormality was seen (18 +/- 15%-19 +/- 19%, P = .66).
      However, for patients with no viable myocardium no significant change in
      diastolic wall-motion abnormality occurred (baseline 45 +/- 12% vs 44 +/- 27% at
      6 months, P = .93). In contrast, a significant decrease was seen for patients
      with viability (33 +/- 16%-22 +/- 23%, P < .001). This was almost exclusively
      caused by normalization of regions where only diastolic wall-motion abnormalities
      were present (19 +/- 11%-7 +/- 15%, P < .0001). In a multivariable regression
      model, myocardial viability (P = .01) and N-terminal pro-brain natriuretic
      peptide concentration on day 3 (P = .003) were associated with changes in
      regional diastolic wall-motion abnormalities. Thus, abnormal diastolic wall
      motion during diastole is frequently present after AMI, and it seems to resolve
      to a greater extent than abnormal systolic wall-motion abnormality especially for
      patients with myocardial viability. This suggests diastolic stunning.

PMID- 16275527
TI  - Emergency nontraumatic chest pain: use of stress echocardiography to detect
      significant coronary artery stenosis.
AB  - OBJECTIVE: We sought to assess the usefulness of stress echocardiography in a
      chest pain department. METHODS: Consecutive patients (n = 487) with nontraumatic
      chest pain, with no signs of myocardial ischemia on arrival to the emergency
      department, 6 and 12 hours later, were recruited. RESULTS: The sensitivity and
      specificity of stress echocardiography in the biased sample were 74% (95%
      confidence interval [CI] 63-85%) and 65% (95% CI 44-86%). After application of
      the method of Begg and Greenes to debias the sample, the calculated sensitivity
      was 24% (95% CI 19-29%) and specificity was 94% (95% CI 91-97%). After
      application of Diamond's method, sensitivity was 32% (95% CI 21-44%) and
      specificity (normalcy rate) was 99% (95% CI 88-100%). CONCLUSIONS: Stress
      echocardiography is an insensitive test when used to detect significant coronary
      artery stenosis in patients presenting with nontraumatic chest pain with no
      objective signs of myocardial ischemia.

PMID- 16275528
TI  - Myocardial blood volume and perfusion reserve responses to combined dipyridamole
      and exercise stress: a quantitative approach to contrast stress echocardiography.
AB  - BACKGROUND: Qualitative interpretation of myocardial contrast echocardiography
      (MCE) improves the accuracy of wall-motion analysis for assessment of coronary
      artery disease (CAD). We examined the feasibility and accuracy of quantitative
      MCE for diagnosis of CAD. METHODS: Dipyridamole/exercise stress MCE (destruction
      replenishment protocol with real-time imaging) was performed in 90 patients
      undergoing quantitative coronary angiography, 48 of whom had significant (> 50%)
      stenoses. MCE was repeated with exercise alone in 18 patients. Myocardial blood
      flow (A*beta) was obtained from blood volume (A) and time to refill (beta).
      RESULTS: Quantification of flow reserve was feasible in 88%. The mean A*beta
      reserve in the anterior wall was significantly impaired for patients with left
      anterior descending coronary artery disease (n = 28) compared with those with no
      disease (1.6 +/- 1.2 vs 4.0 +/- 2.5, P < or = .001). This reflected impaired beta
      reserve, with no difference in the A reserve. Applying a receiver operating
      characteristic curve derived cutoff of 2.0 for A*beta reserve, quantitative MCE
      was 76% sensitive and 71% specific for the diagnosis of significant left anterior
      descending coronary artery stenosis. Posterior circulation results were similar,
      with 78% sensitivity and 59% specificity for detection of posterior CAD. Overall,
      quantitative MCE was similarly sensitive to qualitative approach for diagnosis of
      CAD (88% vs 93%), but with lower specificity (52% vs 65%, P = .07). In 18
      patients restudied with pure exercise stress, the mean myocardial blood flow
      reserve was less than after combined stress (2.1 +/- 1.6 vs 3.7 +/- 1.9, P =
      .01). CONCLUSION: Quantitative MCE is feasible for the diagnosis of CAD with
      dipyridamole/exercise stress. Dipyridamole prolongs postexercise hyperemia,
      augmenting the degree of hyperemia at the time of imaging.

PMID- 16275529
TI  - Can contrast dobutamine stress echocardiography be performed with standardized
      imaging settings for everybody?
AB  - OBJECTIVE: The objective was to assess a standardized imaging and contrast
      injection protocol for contrast-enhanced dobutamine stress echocardiography
      (DSE). METHODS: A total of 102 patients underwent DSE with tissue harmonic
      imaging and a standardized protocol with contrast power modulation. Contrast
      intensities in the left ventricular cavity and the myocardium were evaluated by a
      visual score and quantitative analysis. RESULTS: Of the contrast studies, 98%
      were diagnostic without modification of the settings. Excellent endocardial
      border definition was found in 93% of the segments with contrast versus 53% with
      tissue harmonic imaging (P < .05). The interobserver agreement in assessing
      segmental wall motion improved from 71.5% to 85.9%. There were no differences
      between the myocardial segments' video intensity in the four- and three-chamber
      views. In the two-chamber view video intensity was lower in the basal segments
      compared with the other segments. CONCLUSION: Power modulation contrast imaging
      can be applied with a completely standardized protocol for DSE in the majority of
      patients with excellent endocardial border definition.

PMID- 16275530
TI  - Improved accuracy of low-power contrast echocardiography for the assessment of
      left ventricular remodeling compared with unenhanced harmonic echocardiography
      after acute myocardial infarction: comparison with cardiovascular magnetic
      resonance imaging.
AB  - BACKGROUND: Assessment of left ventricular (LV) remodeling after acute myocardial
      infarction (AMI) has both therapeutic and prognostic implications. Low-power
      contrast echocardiography (CE) has the advantage of simultaneously assessing
      myocardial perfusion and LV remodeling. OBJECTIVE: This study aimed to evaluate
      the accuracy of low-power CE to assess LV remodeling after AMI compared with
      unenhanced harmonic echocardiography (HE). METHODS: A total of 36 consecutive
      patients underwent HE, CE (SonoVue), and cardiovascular magnetic resonance (CMR)
      imaging 7 to 10 days after AMI. Left ventricular ejection fraction (LVEF), end
      systolic volume (LVESV), and end-diastolic volume (LVEDV) were assessed. RESULTS:
      Absolute differences for LVESV and LVEDV between CMR and CE were significantly
      smaller than those between CMR and HE. CE estimate of LVEF more accurately
      classified patients into LVEF < 35%, 35% to 45%, and > 45% (agreement, 83%; kappa
      = 0.66 with CMR) compared with HE (agreement, 69%; kappa = 0.33 with CMR).
      CONCLUSIONS: Low-power CE is more accurate than HE for estimating LV remodeling
      after AMI.

PMID- 16275531
TI  - The efficacy of real-time 3-dimensional echocardiography for right ventricular
      biopsy.
AB  - BACKGROUND: In recipients of cardiac transplant, repetitive right ventricular
      (RV) biopsies can result in decreased sample quality as a consequence of fibrosis
      from oversampling specific locations. Real-time 3-dimensional echocardiography
      (RT3D) is a new imaging modality that may precisely guide bioptome placement and,
      therefore, is a potential alternative to fluoroscopy (Fl). We sought to determine
      if a RT3D-guided biopsy procedure would result in a comparable or decreased
      incidence of fibrosis versus Fl. METHODS: Fifteen patients underwent 32 RV biopsy
      procedures with an equal number by each technique. RT3D was performed from the
      apical 4-chamber position. Fl was performed with biplane images. With both RT3D
      and Fl, attempts were made to vary bioptome position with each sample. A
      pathologist determined the percent fibrosis, with a biopsy sample containing 50%
      or more fibrosis considered uninterpretable for rejection. RESULTS: RT3D provided
      excellent visualization of the distal end of the bioptome within the right atrium
      and RV. A mean of 4.3 +/- 1.0 RV biopsy samples were collected per procedure with
      64 samples obtained by Fl and 72 obtained by RT3D. In all, 13 samples (20.3%) by
      Fl versus 10 samples (13.9%) by RT3D (P = .45) contained fibrosis and 7 samples
      (10.9%) by Fl versus 4 samples (5.6%) were uninterpretable (P = .41). Two Fl-
      versus zero RT3D-guided procedures contained 75% or more uninterpretable samples
      (P = .47) and were, therefore, nondiagnostic. There were no complications.
      CONCLUSIONS: RT3D is a new modality to facilitate accurate localization of the
      bioptome in patients undergoing transplant providing comparable quality RV
      samples to that of biplane Fl.

PMID- 16275532
TI  - Cardioprotective effects of the novel selective endothelin-A receptor antagonist
      BSF 461314 in ischemia-reperfusion injury.
AB  - OBJECTIVE: The aims of the study were to visualize the dynamics of ischemia
      reperfusion injury by real-time myocardial contrast echocardiography and to
      investigate the cardioprotective effects of the novel endothelin-A receptor
      antagonist BSF 461314. BSF 461314 reduced infarct size by 47% and preserved
      microvascular integrity. Real-time myocardial contrast echocardiography allowed
      visualization of postischemic microvascular dysfunction and quantification of
      cardioprotective effects of selective endothelin antagonism. Blood flow index A x
      beta was reduced in anterior segments during ischemia compared with baseline
      (0.06 +/- 0.01 vs 0.98 +/- 0.2 dB/s) but was higher in the BSF 461314 group after
      120 minutes of reperfusion (0.7 +/- 0.08 vs 0.3 +/- 0.05 dB/s, P = .015).
      Therefore, selective endothelin-A receptor antagonism improved microvascular
      integrity during postischemic reperfusion. Real-time myocardial contrast
      echocardiography accurately detected changes in microvascular reflow. BACKGROUND:
      Endothelin-1 is a potent vasoconstrictor and elevated in myocardial ischemia. The
      aims of the study were to examine cardioprotective effects of the novel selective
      endothelin-A receptor antagonist BSF 461314 and to visualize changes in the
      microvasculature by real-time myocardial contrast echocardiography (MCE).
      METHODS: A total of 16 open-chest pigs underwent 45 minutes of left anterior
      descending coronary artery occlusion followed by 120 minutes of reperfusion. A
      total of 1 mg/kg BSF 461314 or vehicle was given intravenously before
      reperfusion. Serial MCE was performed to assess changes in myocardial blood flow
      A x beta and perfusion defect size. Myocardial blood flow was measured by
      fluorescent microspheres and infarct size was measured by triphenyltetrazolium
      chloride tissue staining. RESULTS: Dynamics of infarct size expansion and tissue
      perfusion were correctly assessed by MCE. A x beta Was reduced in anterior
      segments during left anterior descending coronary artery occlusion (0.06 +/- 0.01
      dB/s) compared with baseline (0.98 +/- 0.2 dB/s), approached higher levels
      postrecanalization (1.2 +/- 0.1 dB/s), but gradually decreased during reperfusion
      (0.3 +/- 0.05 dB/s, P < .01). After 120 minutes of reperfusion A (2.1 +/- 0.5 vs
      1.0 +/- 0.6 dB, P < .03), beta (0.36 +/- 0.09/s vs 0.21 +/- 0.09/s, P = .01), and
      A x beta (0.7 +/- 0.08 vs 0.3 +/- 0.05 dB/s, P = .015) in the risk area were
      higher in the BSF 461314-treated group compared with vehicle indicating preserved
      myocardial perfusion. Triphenyltetrazolium chloride staining confirmed a 47%
      reduction in infarct size by BSF 461314. CONCLUSIONS: Selective endothelin-A
      receptor antagonism improved microvascular integrity during postischemic
      reperfusion. Real-time MCE allows visual and quantitative evaluation of dynamics
      of myocardial ischemia-reperfusion injury and monitoring of cardioprotective
      effects during pharmacologic interventions.

PMID- 16275533
TI  - Aneurysm of right atrium diagnosed by 3-dimensional real-time echocardiogram.
AB  - We describe a case of giant aneurysm of right atrium in a child with a previous
      diagnosis of Ebstein's anomaly of tricuspid valve. Three-dimensional real-time
      echocardiography provided more precise anatomic detail of the tricuspid valve,
      right atrium, and right ventricle than did its 2-dimensional counterpart.

PMID- 16275535
TI  - Left ventricular geometry and myocardial contractility in patients with essential
      hypertension evaluated by myocardial velocity profile.
AB  - BACKGROUND: Left ventricular (LV) systolic function in the hypertensive heart has
      been evaluated considering geometric differences. The maximal systolic myocardial
      velocity gradient (Gmax) obtained from myocardial velocity profile can evaluate
      regional myocardial contractility. The purpose of this study was to assess LV
      myocardial contractility in the hypertensive heart using Gmax regarding geometric
      differences. METHODS: The study included 93 patients with essential hypertension.
      Gmax was correlated with relative wall thickness and LV mass index. LV myocardial
      contractility was assessed by classifying patients into normal geometry,
      concentric remodeling (CR), eccentric hypertrophy, and concentric hypertrophy
      (CH). RESULTS: Gmax has shown significant negative relationship with LV end
      diastolic dimension. LV end-diastolic dimension in CH and eccentric hypertrophy
      groups was significantly greater than that in normal geometry and CR groups (CH
      vs CR, 4.9 vs 4.2 cm, P < .001). LV mass index was significantly greater in CH
      and eccentric hypertrophy groups than in the other groups (CH vs CR, 196 vs 122
      g/m2, P < .001). Although there was no difference in relative wall thickness
      between CH and CR groups, Gmax was significantly smaller in CH than in CR group
      (1.8 vs 2.8 s(-1), P < .05). CONCLUSIONS: In patients with essential
      hypertension, LV myocardial contractility worsened corresponding to increase in
      LV dimension with similar wall thickness. Gmax obtained from myocardial velocity
      profile detected depressed myocardial contractility in patients with increased LV
      dimension.

PMID- 16275534
TI  - Role of transesophageal echocardiography in patients with suspected aortic
      dissection.
AB  - Patients with acute aortic dissection of the ascending aorta benefit from rapid
      surgical intervention. We report a patient with suspected acute aortic dissection
      based on history and transthoracic echocardiography findings. This patient was
      taken to the operating room without further workup, where transesophageal
      echocardiography (TEE) revealed acute myocardial infarction and mitral
      regurgitation due to papillary muscle rupture. The patient underwent coronary
      bypass grafting and mitral valve replacement. This case demonstrates that
      intraoperative TEE can be used as a primary diagnostic modality to rule out
      aortic dissection, and can provide a definitive etiology for cardiogenic shock
      before a planned surgical intervention.

PMID- 16275536
TI  - Expanding the use of intracardiac echocardiography in congenital heart disease
      catheter-based interventions.

PMID- 16275537
TI  - Coronary disease in the puerperium.
AB  - The manifestation of an acute coronary syndrome in women in the postpartum period
      is a rare but important clinical scenario, which, because of its multiple
      possible aetiologies, requires a different approach to management on the part of
      the clinician. Spontaneous coronary artery dissection (SCAD) is the most likely
      cause of an acute coronary syndrome in women in the puerperium. Unfortunately
      there is no medical consensus on the correct management pathway of such patients,
      but there is evidence that these patients have an improved prognosis when
      referred for bypass surgery or percutaneous intervention.

PMID- 16275538
TI  - Gallstones in pregnancy and their complications: postpartum acute pancreatitis
      and acute peritonitis.

PMID- 16275539
TI  - Acquired amegakaryocytic thrombocytopenic purpura: review of a not very well
      defined disorder.
AB  - Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a hematological
      disorder characterized by severe thrombocytopenia, probably due to an
      immunologically induced absence of megakaryocytes with a marked decrease or total
      absence of megakaryocytes in the bone marrow. AATP may be differentiated from
      other causes of peripheral destruction of platelets, such as immune
      thrombocytopenia (ITP). Currently, there are no standard treatments for AATP.
      However, immunosuppressive therapy including steroids, androgens, anti-thymocyte
      globulin (ATG), cyclophosphamide, cyclosporine A, immunoglobulins, splenectomy,
      and allogenic bone marrow transplantation (BMT) have all been utilized with
      varying degrees of success. However, a positive response in patients with AATP
      using steroids alone has rarely been reported in the literature.

PMID- 16275540
TI  - Reported parental age of death in type 2 diabetic patients with and without
      established diabetic nephropathy.
AB  - BACKGROUND: Diabetic patients with renal disease have increased mortality,
      largely from cardiovascular disease. This could be related to insulin resistance
      or to other inherited factors. The aim of the present study was to investigate
      whether there is evidence of the familial aggregation of increased mortality,
      even in the absence of diabetes, by studying the reported parental age of death
      in type 2 diabetes. METHODS: Patients with type 2 diabetes and nephropathy (group
      A), patients with type 2 diabetes but without nephropathy (group B) and normal
      controls (group C) were interviewed and asked to report the age of death of their
      parents. RESULTS: The mean (+/-standard deviation) parental age of death was 68.2
      (+/-13.8) years in group A, 67.3 (+/-16.0) years in group B and 68.1 (+/-14.9)
      years in group C. There was no statistical difference between any of the groups.
      CONCLUSION: Our preliminary study has failed to show evidence of reduced life
      expectancy of parents of patients with type 2 diabetes and nephropathy.

PMID- 16275541
TI  - Decreasing the use of anaerobic culture bottles in selected febrile patients--is
      it reasonable?
AB  - BACKGROUND: Two sets of blood cultures are routinely obtained from febrile
      patients in the medical wards. The purpose of the present study was to evaluate
      the distribution of the aerobic versus anaerobic isolates in such patients and to
      examine the rationale of reducing the number of anaerobic culture bottles in
      selected patients. METHODS: A retrospective analysis was performed of all febrile
      patients admitted to medical wards during 1998. Febrile patients from whom at
      least two sets of blood cultures were drawn and who had a bacterial isolation in
      at least one bottle were included. RESULTS: A total of 317 patients were included
      in the analysis. Some 98.5% of all isolates were aerobic pathogens. Only 1.5% of
      all isolates (5/317) included obligatory anaerobes. The rate of isolation in a
      single anaerobic bottle was 8.5%. Analysis of the available files of patients
      with a single anaerobic positive bottle demonstrated that an adequate
      antibacterial agent was administered empirically in most of the cases (93%).
      CONCLUSIONS: We conclude that in carefully selected medical patients suspected of
      having an infectious disease, it is reasonable to obtain one anaerobic and two
      aerobic bottles rather than two full sets. Such an approach is clinically safe
      and will cut expenses on culture bottles and laboratory staff work. This approach
      should be examined in a prospective, randomized study.

PMID- 16275542
TI  - False positivity for Aspergillus antigenemia related to the administration of
      piperacillin/tazobactam.
AB  - BACKGROUND: Invasive aspergillosis is a challenge to the internist, and
      difficulties diagnosing the disease remain an everlasting problem. METHODS: We
      reviewed the data of 65 patients with hematological malignancies and aplastic
      anemia who were tested for the galactomannan (GM) antigen of Aspergillus between
      March and November 2003. RESULTS: GM antigen levels were false-positive in at
      least two consecutive samples in 5 out of 23 patients who did not have evidence
      of invasive aspergillosis (false positivity rate of 21.7%) but who received
      concomitant piperacillin/tazobactam (P/T) compared to 0 of 28 patients who did
      not. DISCUSSION: The use of P/T in febrile, neutropenic patients decreases the
      specificity of GM antigen testing, which may lead to incorrect and unnecessary
      attempts at diagnosis and therapy.

PMID- 16275543
TI  - Pseudocholinesterase polymorphism in an Irish population.
AB  - BACKGROUND: Pseudocholinesterase polymorphism, as an example of pharmacogenetics
      with important clinical implications, has been widely studied and documented.
      However, data on a sample Irish population is lacking. We sought to provide this.
      METHOD: In an assay involving Ellman's reaction, pseudocholinesterase activity,
      alone and with dibucaine or fluoride as an inhibitor, was quantified using
      propionylthiocholine iodide as substrate. RESULTS: Pseudocholinesterase
      activities of 1.13-12.71 U/ml (mean +/- SD 6.74 +/- 2.04 U/ml) showed a normal
      distribution among our 116 healthy, non-medicated volunteers, aged 11-80 years
      (30.7 +/- 10.5 years) and weighing 46-114.6 kg (66.8 +/- 11.4 kg). However,
      dibucaine numbers from an inhibition study yielded a trimodal pattern consistent
      with the hypothesis of two allelic genes. Using an established nomenclature, 92
      (79.3%) of our volunteers were homozygous for the usual form of the enzyme
      (E1uE1u). Of the 13 genotyped as E1uE1a, it is possible that 3 were misclassified
      and are probably E1kE1a. Only one volunteer was homozygous for the atypical form
      of the enzyme, with activity of 1.13 U/ml and dibucaine and fluoride number of
      18.2 and 82.8, respectively. CONCLUSION: The continuous variation in
      pseudocholinesterase activity and the trimodal pattern of dibucaine numbers are
      both in accord with observations in other population groups. Although dibucaine
      number yields a trimodal pattern, its use could lead to misclassification of some
      E1kE1a as E1uE1a.

PMID- 16275544
TI  - Serological profile of HBV infection and liver histopathology among injecting
      drug users with chronic HCV infection in Greece.
AB  - BACKGROUND: The aim of this study was to evaluate the serological status of HBV
      infection and liver histology in chronic HCV-infected injecting drug users (IDUs)
      and to correlate them with the possible time of infection and the principal HCV
      genotype. METHODS: Some 130 prior IDUs with chronic HCV infection were
      consecutively evaluated for the serological status of HBV infection. Fifty-eight
      (44.62%) reported intravenous drug use beginning before 1992 (group A) and 72
      (55.38%) after 1992 (group B). HCV genotyping was available in 86 patients (PCR).
      Liver biopsy was performed in 48 patients (Ishak scoring system). There was no
      available data about alcohol consumption in the study population. Statistical
      analysis was based on the t-test and the chi(2) test (p<0.05). RESULTS: Some
      82.8% of group A patients had previous HBV infection, whereas only 22.2% of group
      B patients did (p<0.001). Among group A patients, 10.3% were HBV-seronegative
      whereas 61.1% of group B patients were (p<0.001). Only 3.4% of group A patients
      were HBV-vaccinated compared to 16.7% in group B (p=0.016). HCV genotype was not
      associated with HBV serological status. No significant differences were detected
      in age, sex, possible time of infection, HBV serological status, or HCV genotype
      among those with higher vs. lower total grading scores. Seventy-five percent of
      patients had mild or no detectable fibrosis unrelated to the possible period of
      infection, the HBV serological status, and the HCV genotype. CONCLUSIONS: The
      serological profile of HBV infection is changing among Greek chronic HCV-infected
      IDUs, while the percentages of successfully HBV-vaccinated IDUs are relatively
      low. Severe liver disease is an uncommon finding in these patients, irrespective
      of the possible time of infection, the HBV serological status, and the HCV
      genotype.

PMID- 16275545
TI  - The dependence of serum interleukin-6 level on PPAR-alpha polymorphism in men
      with coronary atherosclerosis.
AB  - BACKGROUND: The association between L162V polymorphism in the gene for peroxisome
      proliferator activated receptor (PPAR) alpha and the development of coronary
      heart disease was examined. METHODS: PPAR-alpha polymorphism was determined in 48
      men with angiographically confirmed coronary atherosclerosis and in 51 healthy
      men. RESULTS: The frequency of the V allele of the L162V polymorphism was four
      times higher in men with atherosclerosis (0.25 in studied group and 0.06 in
      controls). The polymorphism was not associated with changes in body mass index,
      lipid pattern, serum adhesion molecules, or vasoactive agents concentrations. The
      effect of the polymorphism on the serum interleukin-6 level (IL-6) was observed
      (p<0.01). The serum IL-6 level was higher in homozygotic than in heterozygotic
      subjects (p<0.02). Multivariate regression analysis showed the existence of a
      relationship between simvastatin therapy and serum IL-6 level (r=0.83; p<0.05) in
      the homozygotic men. While in homozygotic patients with atherosclerosis a
      negative linear correlation between serum IL-6 and NO concentration was shown, in
      heterozygotic men positive correlations between IL-6 or HDL cholesterol and
      adhesion molecule levels were found. CONCLUSION: L162V polymorphism in the gene
      for PPAR-alpha seems to be associated with atherosclerosis through a mechanism
      including regulation of the IL-6 level.

PMID- 16275546
TI  - Patients with MEN-1 are more insulin-resistant than their non-affected relatives.
AB  - BACKGROUND: Given the clinical impression that patients with type 1 multiple
      endocrine neoplasia (MEN-1) frequently display abnormal glucose and lipoprotein
      concentrations, we compared affected subjects followed in our outpatient clinic
      with their non-affected relatives. METHODS: The clinical histories of 35 members
      (19 affected) from six families with MEN-1 were reviewed. Total cholesterol,
      triglycerides, insulin, glucose, and insulin resistance (homeostasis model) were
      compared in affected and non-affected subjects. RESULTS: The affected subjects
      displayed higher total cholesterol and triglycerides and more insulin resistance.
      CONCLUSION: Patients with MEN-1 seem to be more insulin-resistant and to have a
      higher cardiovascular risk than their non-affected relatives. Three non
      exclusive, biologically plausible hypotheses are proposed.

PMID- 16275547
TI  - Henoch-Schonlein purpura presenting as terminal ileitis and complicated by
      thrombotic microangiopathy.
AB  - We report here on a 40-year-old woman with abdominal pain, low-grade fever, and
      diarrhea in whom the cutaneous features of Henoch-Schonlein purpura (HSP)
      appeared only a few days after acute abdominal symptoms. Endoscopy showed
      terminal ileitis, and histopathological examination of a biopsy of the ileum
      showed a picture of IgA vasculitis. The clinical course was further complicated
      by the development of microangiopathic hemolytic anemia, thrombocytopenia, and
      severe renal failure.

PMID- 16275548
TI  - Recurrent herpes simplex encephalitis.
AB  - Recurrent herpes simplex virus (HSV) encephalitis is a rare disorder with only a
      few cases reported. We report a case of HSV encephalitis with documented
      recurrence in the same anatomic location, lending support to the theory of
      reactivation as the mechanism of disease.

PMID- 16275549
TI  - Cardiac tamponade associated with an elevated arterial blood pressure.
AB  - A 30-year-old male presented with acute pericarditis and a moderate pericardial
      effusion. His condition deteriorated suddenly with a marked elevation in blood
      pressure. The hypertension was erroneously correlated with a low probability of
      cardiac tamponade, leading to a delay in performing an echocardiogram. The
      echocardiogram subsequently showed features of cardiac tamponade. Severe
      elevation of blood pressure in a patient with cardiac tamponade is a rare and
      under-recognized disorder. This condition is discussed here.

PMID- 16275550
TI  - Bartonella quintana endocarditis in east Africa.
AB  - Bartonella quintana endocarditis is characterized by sub-acute evolution and
      severe valvular damage, and is associated with homelessness, alcoholism, and lice
      infestation. We present a case of B. quintana endocarditis in an Ethiopian
      immigrant without known risk factors for disease acquisition. This is the first
      case of B. quintana endocarditis reported from east Africa.

PMID- 16275551
TI  - Lone atrial septal aneurysm and stroke--a case report and review of the
      literature.
AB  - The aetiology of stroke in young patients is usually difficult to establish.
      Despite extensive investigations, the cause of stroke remains unknown in a large
      percentage of these patients. We report a case of stroke in a young patient in
      whom the only associated aetiological factor was a lone atrial septal aneurysm.
      We discuss the investigational tools in the diagnosis of atrial septal aneurysms
      and study the aetiopathogenesis of strokes and the risk of recurrent strokes
      associated with their presence. We also review the evidence for the presently
      available therapies for prevention of further strokes in such patients.

PMID- 16275552
TI  - Malignant thymoma complicated by amegakaryocytic thrombocytopenic purpura.
AB  - We report the case of a 41-year-old man with malignant thymoma complicated by
      amegakaryocytic thrombocytopenia 10 years after diagnosis of myasthenia gravis. A
      bone marrow aspirate showed an absence of megakaryocytes with normal maturation
      and differentiation of myeloid precursors. Three months later, severe neutropenia
      occurred, and a bone marrow examination confirmed the diagnosis of severe
      aplastic anemia. Associations between thymoma and myasthenia gravis, between
      thymoma and pure red cell aplasia, and between thymoma and aplastic anemia are
      well documented. Amegakaryocytic thrombocytopenia is not a recognized
      paraneoplastic syndrome complicating thymoma. Amegakaryocytic thrombocytopenia
      complicating thymoma may be a very early presentation of impending aplastic
      anemia.

PMID- 16275553
TI  - Cerebral infarction: an unusual complication of Mediterranean spotted fever.
AB  - Mediterranean spotted fever is a rickettsiosis caused by Rickettsia conorii and
      transmitted by the brown dog tick. It is considered as a benign disease but 5% to
      10% of patients present with a malignant form which is the result of a diffuse
      vasculitis. We report here the first case of Mediterranean spotted fever with
      cerebral vasculitis and thrombosis leading to a massive cerebral infarct and
      death.

PMID- 16275554
TI  - Epstein-Barr virus-associated pericarditis and pericardial effusion: case report
      and diagnostic aspects.
AB  - We report the case of a 39-year-old patient suffering from acute pericarditis
      accompanied by considerable pericardial effusion, most probably secondary to
      acute Epstein-Barr virus infection, an etiology uncommonly reported with
      pericardial inflammation and effusion. Diagnostic aspects and the approach to
      etiologic evaluation are discussed.

PMID- 16275555
TI  - Primary unilateral tuberculous inguinal lymphadenitis.
AB  - We report the case of a young Greek woman who presented with erythema nodosum and
      isolated unilateral inguinal lymphadenopathy. Excision and biopsy of the lymph
      node showed infection due to M. tuberculosis. An extensive workup did not reveal
      any other foci of tuberculosis. Isolated tuberculous inguinal lymphadenitis is a
      rare entity in developed countries and is almost always bilateral. Our case is
      unique because the disease was unilateral and affected an otherwise healthy woman
      who had never traveled in endemic areas.

PMID- 16275557
TI  - Lymphocytic pleural effusion associated with valproic acid.

PMID- 16275556
TI  - Combined Brucella melitensis and Staphylococcus aureus endocarditis in a patient
      with a prosthetic aortic valve with fatal outcome.

PMID- 16275558
TI  - Sarcoidosis type II and IgG autoantibodies-induced hemolysis in a 64-year-old
      woman.

PMID- 16275559
TI  - Etiology of anemia in critically ill patients: role of red blood cell rheology.

PMID- 16275560
TI  - Pitfalls in normalization for intensity-modulated radiation therapy planning.
AB  - Three-dimensional (3D) treatment planning often involves complex combinations of
      beam energies, treatment fields, and beam modifying devices. Even when a plan is
      devised that meets many treatment-planning objectives, limitations in the
      planner's ability to further adjust beam characteristics may require the
      radiation dose prescription to be normalized to an isodose level that best covers
      the target volume. While these normalizations help meet the volume coverage
      goals, they also result in adjustment of the dose delivered to the normal tissues
      and must be carefully evaluated. Intensity-modulated radiation therapy (IMRT)
      treatment planning allows combinations of complex dose patterns, in order to
      achieve the desired treatment planning goals. These dose patterns are created by
      defining a set of treatment planning objectives and then allowing the treatment
      planning computer to create intensity patterns, through the use of moving
      multileaf collimation that will meet the requested goals. Often, when an IMRT
      treatment plan is created that meets many of the treatment planning goals but
      falls short of volume coverage requirements, the planner is tempted to apply
      normalization principles similar to those utilized with 3D treatment planning.
      Again, these normalizations help meet the volume coverage goals, but unlike 3D
      planning situations, may result in avoidable delivery of additional doses to the
      normal tissues. The focus of this study is to evaluate the effect of application
      of normalization for IMRT planning using multiple patient situations.
      Recommendations would favor re-optimization over normalization in most planning
      situations.

PMID- 16275561
TI  - IMRT fluence map editing to control hot and cold spots.
AB  - Manually editing intensity-modulated radiation therapy (IMRT) fluence maps
      effectively controls hot and cold spots that the IMRT optimization cannot
      control. Many times, re-optimizing does not reduce the hot spots or increase the
      cold spots. In fact, re-optimizing only places the hot and cold spots in
      different locations. Fluence-map editing provides manual control of dose delivery
      and provides the best treatment plan possible. Several IMRT treatments were
      planned using the Varian Eclipse planning system. We compare the effects on dose
      distributions between fluence-map editing and re-optimization, discuss techniques
      for fluence-map editing, and analyze differences between fluence editing on one
      beam vs. multiple beams. When editing a beam's fluence map, it is essential to
      choose a beam that least affects dose to the tumor and critical structures.
      Editing fluence maps gives an advantage in treatment planning and provides
      controlled delivery of IMRT dose.

PMID- 16275562
TI  - Optimization of collimator parameters to reduce rectal dose in intensity
      modulated prostate treatment planning.
AB  - The inability to avoid rectal wall irradiation has been a limiting factor in
      prostate cancer treatment planning. Treatment planners must not only consider the
      maximum dose that the rectum receives throughout a course of treatment, but also
      the dose that any volume of the rectum receives. As treatment planning techniques
      have evolved and prescription doses have escalated, limitations of rectal dose
      have remained an area of focus. External pelvic immobilization devices have been
      incorporated to aid in daily reproducibility and lessen concern for daily patient
      motion. Internal immobilization devices (such as the intrarectal balloon) and
      visualization techniques (including daily ultrasound or placement of fiducial
      markers) have been utilized to reduce the uncertainty of intrafractional prostate
      positional variation, thus allowing for minimization of treatment volumes.
      Despite these efforts, prostate volumes continue to abut portions of the rectum,
      and the necessary volume expansions continue to include portions of the anterior
      rectal wall within high-dose regions. The addition of collimator parameter
      optimization (both collimator angle and primary jaw settings) to intensity
      modulated radiotherapy (IMRT) allows greater rectal sparing compared to the use
      of IMRT alone. We use multiple patient examples to illustrate the positive
      effects seen when utilizing collimator parameter optimization in conjunction with
      IMRT to further reduce rectal doses.

PMID- 16275563
TI  - Characterization of responses and comparison of calibration factor for commercial
      MOSFET detectors.
AB  - A commercial metal oxide silicon field effect transistor (MOSFET) dosimeter of
      model TN502-RD has been characterized for its linearity, reproducibility, field
      size dependency, dose rate dependency, and angular dependency for Cobalt-60
      (60Co), 6-MV, and 15-MV beam energies. The performance of the MOSFET clearly
      shows that it is highly reproducible, independent of field size and dose rate.
      Furthermore, MOSFET has a very high degree of linearity, with r-value>0.9 for all
      3 energies. The calibration factor for 2 similar MOSFET detectors of model TN502
      RD were also estimated and compared for all 3 energies. The calibration factor
      between the 2 similar MOSFET detectors shows a variation of about 1.8% for 60Co
      and 15 MV, and for 6 MV it shows variation of about 2.5%, indicating that
      calibration should be done whenever a new MOSFET is used. However, the detector
      shows considerable angular dependency of about 8.8% variation. This may be due to
      the variation in radiation sensitivity between flat and bubble sides of the
      MOSFET, and indicates that positional care must be taken while using MOSFET for
      stereotactic radiosurgery and stereotactic radiotherapy dosimetric applications.

PMID- 16275565
TI  - Implementation of enhanced dynamic wedges in Pinnacle treatment planning system.
AB  - Enhanced dynamic wedges (EDW) provide many advantages over traditional hard
      wedges for linear accelerator treatments. Along with these advantages comes the
      responsibility of ensuring that this complex technology delivers the correct dose
      to patients. This involves determining the enhanced dynamic wedge factors for
      various field sizes and depths for use in the hand calculation of monitor units
      (MUs). The accurate representation of dynamic wedges in the treatment planning
      computer must also be ensured. This is required so that the final isodose
      distributions are correct and the MUs calculated by the treatment planning
      computer match those determined by hand calculation. We have commissioned and
      implemented the use of EDW in the Pinnacle radiation therapy planning system. The
      modeled dose profiles agree with the measured ones with a maximum difference of
      2%. The MUs generated by Pinnacle are also within 2% of those calculated
      independently. The process of data collection and verification, beam modeling,
      and a discussion of a potential pitfall encountered in this process are presented
      in this paper.

PMID- 16275564
TI  - Comparative dosimetric study of two strategies of intensity-modulated
      radiotherapy in nasopharyngeal cancer.
AB  - This study compared the target volume coverage and normal tissues sparing of
      simultaneous integrated boost (SIB-IMRT, 1-phase) and sequential-IMRT (2-phase)
      for nasopharyngeal carcinoma (NPC). Fourteen consecutive patients with newly
      diagnosed primary NPC were enrolled in this study. The CT images were transferred
      to a commercial planning system for structural delineation. The gross tumor
      volume (GTV) included gross nasopharyngeal tumor and involved lymph nodes of more
      than 1-cm diameter. The clinical target volume (CTV) modeled two regions
      considered to represent different risks. CTV1 encompassed the GTV with 5-10-mm
      margin of adjacent tissues. CTV2 encompassed ipsilateral or contralateral
      elective nodal regions at risk of harboring microscopic tumor. A commercial IMRT
      treatment planning system (Eclipse Version 7.1) was used to provide treatment
      planning. Seven fixed-gantry (0 degrees, 50 degrees, 100 degrees, 150 degrees,
      210 degrees, 260 degrees, 310 degrees ) angles were designated. The 14 patients
      were treated with sequential-IMRT, and treatment was then replanned with an SIB
      strategy to compare the dosimetric difference. For the sequential strategy, the
      dose delivered to CTV1/CTV2 in the first course was 54 Gy (1.8 Gyx30 Fr); while
      CTV1 was boosted by an additional 16.2 Gy (1.8 Gyx9 Fr) in the second course. For
      SIB-IMRT, the dose prescribed to CTV1 was 69.7 Gy (2.05 Gyx34 Fr); 56.1 Gy was
      given to CTV2 (1.65 Gyx34 Fr). A statistical analysis of the dose-volume
      histogram of target volumes and critical organs was performed. Paired Student's t
      test was used to compare the dosimetric differences between the two techniques.
      The mean dose to CTV1 was 101.7+/-2.4% and 102.3+/-3.1% of the prescribed dose
      for SIB-IMRT and sequential-IMRT, respectively. The mean CTV2 dose was 109.8+/
      4.7% of the prescribed dose for SIB-IMRT and 112.6+/-6.0% of the prescribed dose
      for sequential-IMRT. The maximal dose to the spinal cord was 4489+/-495 cGy and
      3547+/-767 cGy for SIB and sequential-IMRT (p=0.0001), respectively. The maximal
      dose to brain stem was significantly higher using SIB technique (5284+/-551 cGy)
      than sequential-IMRT (4834+/-388 cGy) (p=0.0001). The mean dose to the parotid
      gland and ear apparatus was significantly lower using SIB-IMRT. The mean dose to
      the right/left parotids was 2865+/-320 cGy/2903+/-429 cGy and 3567+/-534
      cGy/3476+/-489 cGy for SIB and sequential-IMRT, respectively (p=0.0001). Target
      coverage was the same for both techniques; the dose distribution in the elective
      nodal area with SIB was superior to that with sequential-IMRT. SIB-IMRT provides
      better sparing of parotid gland and inner ear structures. Extra caution should be
      taken when applying SIB-IMRT since critical organs close to the boost volume may
      receive higher doses.

PMID- 16275566
TI  - Elements of commissioning step-and-shoot IMRT: delivery equipment and planning
      system issues posed by small segment dimensions and small monitor units.
AB  - The implementation of intensity-modulated radiation therapy (IMRT) in the clinic
      necessitates commissioning for all systems involved. This paper describes work
      carried out for the treatment planning system (Helax-TMS version 6.1) and the
      treatment delivery equipment (Siemens Primus) available at our center. Particular
      regard was paid to small monitor units (MUs) and small field segments typical of
      step-and-shoot IMRT plans. The beam profile stability of the Siemens Primus
      accelerators when delivering small MU was examined with a linear detector array.
      Dose monitor linearity and intersegment variations were measured with a 0.6-cm3
      ionization chamber. Treatment planning system calculated total scatter factors
      (Scp) and beam profiles for symmetric and asymmetric small fields for 6- and 15MV
      beams were compared against measurements in water using a 0.125-cm3 ionization
      chamber and a diamond detector. The 6- and 15MV beams from the Primus
      accelerators were found to be stable at MUs less than 10. Dose monitor linearity
      for small exposures under 10 MU was within+/-2% for 6 MV, but found to be not so
      initially for 15 MV. This could be remedied by an adjustment of a soft spot on
      the Siemens Primus. The delivery of small MU segments as part of an IMRT sequence
      was found to be consistent down to segment sizes of 1 MU. The treatment planning
      system pencil-beam convolution model agreed with measurement within+/-5% for
      fields collimated down to 3x3 cm. The collapsed cone point-kernel model better
      predicted the output for the smallest field, but displayed some unpredictable
      shifts in the position of the penumbra. The startup characteristics of Siemens
      Primus accelerators were found suitable for step-and-shoot IMRT. The diminution
      in accuracy of Helax-TMS dose calculation models for multileaf collimated fields
      of less than 2x2 cm has led us to avoid these in IMRT treatments at our center.

PMID- 16275567
TI  - Quality assurance of HDR prostate plans: program implementation at a community
      hospital.
AB  - Adenocarcinoma of the prostate is currently the most commonly diagnosed cancer in
      men in the United States, and the second leading cause of cancer mortality. The
      utilization of radiation therapy is regarded as the definitive local therapy of
      choice for intermediate- and high-risk disease, in which there is increased risk
      for extracapsular extension, seminal vesicle invasion, or regional node
      involvement. High-dose-rate (HDR) brachytherapy is a logical treatment modality
      to deliver the boost dose to an external beam radiation therapy (EBRT) treatment
      to increase local control rates. From a treatment perspective, the utilization of
      a complicated treatment delivery system, the compressed time frame in which the
      procedure is performed, and the small number of large dose fractions make the
      implementation of a comprehensive quality assurance (QA) program imperative. One
      aspect of this program is the QA of the HDR treatment plan. Review of regulatory
      and medical physics professional publications shows that substantial general
      guidance is available. We provide some insight to the implementation of an HDR
      prostate plan program at a community hospital. One aspect addressed is the
      utilization of the low-dose-rate (LDR) planning system and the use of existing
      ultrasound image sets to familiarize the radiation therapy team with respect to
      acceptable HDR implant geometries. Additionally, the use of the LDR treatment
      planning system provided a means to prospectively determine the relationship
      between the treated isodose volume and the product of activity and time for the
      department's planning protocol prior to the first HDR implant. For the first 12
      HDR prostate implants, the root-mean-square (RMS) deviation was 3.05% between the
      predicted product of activity and time vs. the actual plan values. Retrospective
      re-evaluation of the actual implant data reduced the RMS deviation to 2.36%.

PMID- 16275570
TI  - MR imaging of the normal hip.
AB  - This article reviews the complex normal anatomy of the hip joint and its
      surrounding structures on MR imaging, including MR arthrography.Thorough
      knowledge of the normal appearance of the marrow and osseous and articular
      anatomy as well as the ligaments, tendons, and surrounding muscles of the hip is
      essential for imaging diagnosis.

PMID- 16275571
TI  - Technical considerations in MR imaging of the hip.
AB  - MR imaging of the hip presents technical difficulties seldom encountered when
      imaging other joints. The imager is responsible for surrounding bony and soft
      tissue structures susceptible to many maladies that can mimic hip pain related to
      an intra-articular derangement. The anatomic nature of the hip and pelvis present
      difficulties with application and use of local receiver coils. A lack of hip
      joint capaciousness and distensibility presents obstacles to acquiring diagnostic
      images with direct and indirect arthrography. Imagers must strive to improve
      diagnostic accuracy and maximize the information provided to referring clinicians
      in each MR imaging report in order to help choose the most appropriate
      therapeutic course. In this article, the authors review technical considerations
      specific to patient subsets and suspected causalgia of pain or dysfunction about
      the hip.

PMID- 16275572
TI  - Role of hip MR imaging in the management of sports-related injuries.
AB  - MR imaging is an invaluable method for the workup of a painful hip. It is showing
      increased sensitivity and specificity for many of the soft tissue and bony
      abnormalities of the hip, especially with the addition of intra-articular
      contrast(MR arthrography). Chondral injuries of the femoral head and acetabulum
      remain an area in MR imaging that should continue to improve with new gradient
      protocols.

PMID- 16275573
TI  - Imaging of the acetabular labrum.
AB  - The acetabular labrum is a critical structure within the hip joint. It is a
      significant cause of pain, and it plays an integral role in the development of
      osteoarthritis. This article reviews the normal anatomy, imaging techniques, and
      normal MR appearance of the labrum. The clinical presentation of labral tears and
      their association with developmental dysplasia and femoroacetabular impingement
      are discussed. The controversy regarding the presence or absence of a sublabral
      sulcus also is addressed.

PMID- 16275574
TI  - MR imaging of femoroacetabular impingement.
AB  - FAI is a common cause of OA of the hip. It can be caused by decreased offset of
      the femoral head and neck, resulting in abutment of the femoral neck against the
      acetabular rim (cam impingement) and abutment of this area into the well
      constrained socket (pincer impingement)within normal range of motion [15]. This
      repetitive mechanical trauma to the hip joint causes mechanical wear of the
      labrum and articular cartilage; left untreated, it causes pain, labral tears, and
      chondral injuries leading to progressive OA of the hip. The identification of FAI
      as a cause of OA allows appropriate therapy early and thus delays or prevents end
      stage arthritis.MR imaging and MR arthrography are accurate noninvasive imaging
      modalities able to demonstrate acetabular labral disease and adjacent cartilage
      damage as well as the subchondral cysts and synovial herniation pits associated
      with impingement. In addition, MR imaging is able to detect underlying subtle
      anatomic variations of the femoral head-neck junction and acetabulum associated
      with FAI.

PMID- 16275575
TI  - MR imaging of the hip: osseous lesions.
AB  - Because of the exquisite soft tissue contrast resolution of MR imaging combined
      with recent technologic developments, a variety of conditions involving the hip
      joint and adjacent bony structures can be well evaluated using MR imaging, with
      or without contrast material. Among the different conditions, hip trauma and
      avascular necrosis are the most frequent indications. Other entities for which MR
      imaging has proven its usefulness include subchondral fractures, osteochondritis
      dissecans, transient osteoporosis, bone tumors, inflammatory and infectious
      processes, and a variety of bone marrow disorders.

PMID- 16275576
TI  - Hamstring injuries of the hip.
AB  - Hamstring injuries can be classified with regard to the site of involvement.
      Traumatic disorders at the proximal bone-tendon origin are best defined as
      avulsion injuries, such as ischial tuberosity fractures and hamstring tendon
      tears. Musculotendinous lesions include muscle strains and muscle contusions.
      Most hamstring injuries occur after in-direct trauma from excessive stretching or
      forceful contraction, leading to avulsion injuries or muscle strains and tears.
      Insufficient warm-up, lack of flexibility, inadequate muscle strength and
      endurance, or abnormal contraction and running may predispose to such injuries.
      In the event of blunt direct trauma, a muscle contusion, intramuscular hematoma,
      myositis ossificans, or compartment syndrome may develop.

PMID- 16275577
TI  - MR imaging of the hip abductors: normal anatomy and commonly encountered
      pathology at the greater trochanter.
AB  - Lateral hip pain, also referred to as the greater trochanteric pain syndrome, is
      a commonly encountered clinical problem with a broad set of differential
      considerations. A detailed understanding of the osseous anatomy of the greater
      trochanter, the correspond-ing attachment sites of the abductors of the hip, and
      the spatial and anatomic relations of their corresponding bursae is crucial to
      the accurate characterization and localization of pathologic findings in these
      structures. This article reviews the anatomy and pathologic findings of the
      osseous and soft tissue anatomy of the greater trochanter.

PMID- 16275578
TI  - MR imaging of iliopsoas musculotendinous injuries.
AB  - The literature describing iliopsoas compartment injuries is based on case reports
      and small patient series, mostly in the orthopedic literature.Nevertheless, in
      recent years, there has been a growing recognition of these injuries. Because
      many intra-articular and extra-articular bony and soft tissue injuries in the
      groin may clinically mimic each other, because two or more pathologic entities
      may coexist, and because athletes are highly motivated to continue with their
      physical activity, diagnosis of iliopsoas injury is often delayed. Thus, cross
      sectional imaging is highly important. MR imaging is most accurate for diagnosing
      nondynamic diseases of the iliopsoas compartment as well as for ruling out other
      abnormalities of the hip joint and surrounding structures. When a snapping hip is
      being investigated or corticosteroid injection is warranted, US can be of help in
      providing a dynamic study and by guiding the injection.

PMID- 16275579
TI  - MR imaging of the proximal rectus femoris musculotendinous unit.
AB  - MR imaging is a useful modality for diagnosing and grading proximal rectus
      femoris injuries.MR imaging is also valuable in predicting the length of recovery
      and rehabilitation time of musculotendinous strains and in presurgical planning
      when resection of a chronic hematoma, deep scar tissue, or a pseudocyst is
      contemplated.

PMID- 16275580
TI  - MR imaging of sports-related groin pain.
AB  - With increasing participation in professional and recreational athletics,
      activity-limiting pelvic and groin pain presents a growing challenge for patients
      and health care providers. The causes of musculoskeletal-related groin pain among
      athletes are diverse, with considerable overlap in history and physical
      examination findings. Pubalgia is a clinical diagnosis invoked when no more
      specific cause ofa patient's symptoms can be determined on history and physical
      examination. In many cases, dedicated MR imaging of the hip and pelvis can
      provide a prompt and specific diagnosis, which allows for early treatment and
      return to participation.

PMID- 16275581
TI  - MR imaging of hip infection and inflammation.
AB  - With its superior anatomical resolution and high sensitivity in depicting
      pathological processes of the joint, bone marrow and surrounding soft tissue
      structures, MR imaging is the ideal modality for demonstrating the manifestations
      and sequelae of the infective and inflammatory conditions common to the hip.
      Though the imaging features of these conditions may overlap, combining the
      clinical history and results and other imaging modalities yields a higher degree
      of specificity, ultimately enhancing the confidence of the radiological
      interpretation.

PMID- 16275582
TI  - MR imaging of tumors and tumor-like lesions of the hip.
AB  - In conclusion, a wide variety of tumors and tumor-like conditions have a
      predilection for the hip. The imaging evaluation of these lesions begins with
      radiographs. Radiographs can depict the extent of disease; any characteristic
      calcifications; and osseous changes, such as remodeling,periosteal reaction, or
      destruction. MR imaging has emerged as the preferred imaging modality of choice
      for evaluating osseous and soft tissue masses of the hip by providing information
      for diagnosis and staging. The MR imaging signal characteristics and enhancement
      patterns of malignant and benign hip tumors permit specific diagnoses in some
      cases. Synovial-based tumor-like processes of the hip can be characterized by MR
      signal characteristics, such as the hemosiderin within PVNS or the cartilage
      within synovial chondromatosis. Finally, MR imaging can serve to exclude
      underlying osseous or soft tissue tumors when radiographs display aggressive
      features of tumor-like processes.

PMID- 16275583
TI  - Morel-Lavallee lesion: review with emphasis on MR imaging.
AB  - MR imaging is the diagnostic imaging modality of choice in the assessment of ML
      lesions in the hip region. Given their typical location, morphology, signal
      behavior, and enhancement pattern,ML lesions can be identified readily on MR
      examinations of the hip and proximal thigh.Correct preoperative MR diagnosis of
      ML lesions can be useful for treatment planning.

PMID- 16275584
TI  - MR imaging of congenital/developmental and acquired disorders of the pediatric
      hip and pelvis.
AB  - This article reviews the MR imaging findings of some of the more common
      congenital and acquired disorders of the pediatric hip and pelvis,with the intent
      of increasing the awareness of radiologists and facilitating early and accurate
      diagnosis and treatment. The importance of MR imaging in the pediatric population
      is underscored by its ability to evaluate these disorders well and without the
      use of ionizing radiation.

PMID- 16275586
TI  - 9th Annual Scientific Meeting of the Japanese Heart Failure Society (JHFS 2005),
      Yamaguchi, Japan, Oct 20-22, 2005. Abstracts.

PMID- 16275585
TI  - Abnormalities in and around the hip: MR imaging versus sonography.
AB  - Sonography and MR imaging should be considered complementary rather than
      competing modalities. They demonstrate similar abnormalities of the soft tissues,
      but MR imaging is able to demonstrate intraosseous and articular abnormalities
      and offers a better anatomic overview because of its larger field of view,
      whereas sonography offers dynamic evaluation and can provide real-time guidance
      for percutaneous procedures. Both of these modalities have roles in the imaging
      evaluation of injuries in and around the hip.

PMID- 16275587
TI  - The evolution of the evidence-based review: evaluating the science enhances the
      art of medicine--statement of the Steering Committee for Evidence-Based Reviews
      of the American Society for Blood and Marrow Transplantation.

PMID- 16275588
TI  - The role of cytotoxic therapy with hematopoietic stem cell transplantation in the
      therapy of acute lymphoblastic leukemia in children: an evidence-based review.
AB  - Evidence supporting the role of hematopoietic stem cell transplantation (SCT) in
      the therapy of acute lymphoblastic leukemia (ALL) in children is presented and
      critically evaluated in this systematic evidence-based review. Specific criteria
      were used for searching the published literature and for grading the quality and
      strength of the evidence and the strength of the treatment recommendations.
      Treatment recommendations based on the evidence are presented in a table in this
      review (Summary of Treatment Recommendations Made by the Expert Panel for
      Pediatric Acute Lymphoblastic Leukemia) and were reached unanimously by a panel
      of ALL experts. The priority areas of needed future research in pediatric ALL are
      unrelated marrow or blood donor versus unrelated cord blood donor allogeneic SCT;
      alternative, nonfamily allogeneic donor versus autologous SCT; better methods for
      identifying high-relapse-risk patients; assessments of the effect of current
      chemotherapy regimens on early relapse; and use of pre-SCT detection of minimal
      residual disease to predict post-SCT outcomes.

PMID- 16275589
TI  - Feasibility of allogeneic hematopoietic stem cell transplantation for autoimmune
      disease: position statement from a National Institute of Allergy and Infectious
      Diseases and National Cancer Institute-Sponsored International Workshop,
      Bethesda, MD, March 12 and 13, 2005.

PMID- 16275590
TI  - The new apheresis and blood and marrow transplantation-related current procedural
      terminology codes for payment of apheresis and blood and marrow transplantation
      services.
AB  - To address deficiencies in Current Procedural Terminology (CPT) codes that
      describe many of the clinical services offered to patients, several physicians in
      the blood and marrow transplantation and apheresis field joined with a coalition
      including the American Society of Hematology, American Society for Blood and
      Marrow Transplantation, American Association of Blood Banks, American Society of
      Clinical Oncology, American Society for Apheresis, National Marrow Donor Program,
      and American Red Cross to collaborate in addressing these deficiencies by
      designing new CPT codes. The CPT editorial panel approved 18 new or revised
      codes. All these codes were given permanent or temporary value by the relative
      value unit update committee, but not all values were approved by the Centers for
      Medicare & Medicaid Services (CMS), in particular, the cell-processing codes and
      the unrelated donor search code. Further discussions addressing these concerns
      are under way with the CMS. Use of these new codes allows apheresis and
      transplant centers to charge appropriately for these services. This will help
      transplant center contracts with CPT codes, with payers more specifically
      describing services offered to these patients. In turn, this will give better
      justification for payment. This may allow certain payments for services to
      increase and help transplant centers better allocate revenue from fixed global
      case rate payments. Details about the individual codes and their approval process
      are reviewed in this article.

PMID- 16275591
TI  - Effect of conditioning regimen on the outcome of bone marrow transplantation from
      an unrelated donor.
AB  - Little information is available regarding the effect of the conditioning regimen
      on the outcome of bone marrow transplantation (BMT) from an unrelated donor.
      Therefore, we retrospectively compared the outcome after a cyclophosphamide/total
      body irradiation (Cy-TBI) regimen, an intensified Cy-TBI regimen (Cy-TBI+), a
      busulfan and cyclophosphamide (Bu-Cy) regimen, and a Bu-Cy regimen with total
      lymphoid irradiation (Bu-Cy-TLI). Clinical data of 1875 adult patients who
      underwent unmanipulated unrelated BMT for leukemia or myelodysplastic syndrome by
      using 1 of the 4 regimens between 1993 and 2002 were extracted from the database
      of the Japan Marrow Donor Program. The effect of the conditioning regimen was
      adjusted for other independent significant factors by multivariate analyses. The
      Cy-TBI regimen was significantly better than the Bu-Cy regimen with regard to the
      incidence of engraftment failure (odds ratio, 2.49; P = .046) and overall
      survival (relative risk [RR], 1.31; P = .050). The Bu-Cy-TLI regimen decreased
      relapse (RR, 0.13; P = .039) but increased nonrelapse mortality (RR, 1.89; P =
      .0061). The Cy-TBI+ regimen resulted in increased nonrelapse mortality (RR, 1.48;
      P = .0003) and inferior survival (RR, 1.45; P < .0001). The results of this
      retrospective study suggested that the Cy-TBI regimen was superior to other
      regimens in unrelated BMT.

PMID- 16275592
TI  - Cytomegalovirus immune reconstitution occurs in recipients of allogeneic
      hematopoietic cell transplants irrespective of detectable cytomegalovirus
      infection.
AB  - The question of when immune reconstitution of cytomegalovirus (CMV)-specific CD8
      T cells occurs after hematopoietic cell transplantation and, more specifically,
      to which CMV targets this immunity is likely to be directed remains poorly
      understood. The dependence of immune reconstitution on CMV reactivation is even
      less clear. To better understand these events, 44 CMV-seropositive HLA-A*0201
      subjects were followed up at approximately days 40, 90, 120, 150, 180, and 360
      after hematopoietic cell transplantation for CMV immunity as measured by 2 types
      of assays: (1) an HLA-A*0201 tetramer-binding assay for both CMV pp65 (pp65) and
      immediate-early 1 (IE-1) or (2) intracellular cytokine interferon gamma responses
      induced by pp65 or IE-1-derived peptides. To verify the reliability of IE-1
      specific assays relative to the pp65-based assays, a pilot study first compared
      the development of IE-1-specific immunity in a subgroup by using multiple HLA
      A*0201-restricted peptides, and then these recipients were followed up for 1 year
      for immunologic function and for CMV infection. The IE-1-specific response
      occurred to each of the 3 HLA-A*0201-restricted peptides studied (IE-1-256, -297,
      and -316), and there was no predominant IE peptide response. However, the
      immunodominant HLA-A*0201-restricted pp65 peptide was recognized significantly
      more frequently than these IE-1 peptides. When this was compared with the
      occurrence of CMV infection, the overall immune reactivity, as measured by the
      mean or median number of CD8+ T cells reactive to either pp65 or IE-1 peptides by
      intracellular cytokine or tetramer binding assay, was not significantly different
      in those with and without CMV infection. For patients who demonstrated
      reconstituted immunity to CMV at 1 year, all were reconstituted by 6 months, and
      the timing of the first observed immune reactivity to either of the pp65 or the
      IE peptides was not different in those with and without detectable CMV infection.

PMID- 16275593
TI  - Paclitaxel-based high-dose chemotherapy with autologous stem cell rescue for
      relapsed germ cell cancer.
AB  - We evaluated the antitumor activity of tandem cycles of high-dose chemotherapy
      with autologous peripheral stem cell transplantation (aPSCT) in relapsed germ
      cell tumors by using high-dose paclitaxel, carboplatin, etoposide, and
      ifosfamide. Thirty-three patients were entered, and 31 underwent protocol
      therapy. Paclitaxel 350 mg/m2 (5 patients) or 425 mg/m2 (26 patients) by 24-hour
      continuous intravenous infusion was followed by 3 daily doses of carboplatin and
      either etoposide (cycle 1) or ifosfamide/mesna (cycle 2). The carboplatin dose
      had a calculated area under the curve of 7 mg-min/mL, and the daily dose of
      etoposide was 20 mg/kg (cycle 1). Ifosfamide 3 g/m2/d for 3 days (with mesna
      uroprotection) was substituted for etoposide in cycle 2. Each cycle was supported
      by granulocyte colony-stimulating factor-mobilized peripheral blood stem cells.
      Thirty-one patients were evaluable for response, toxicity, and long-term disease
      control. Two patients did not undergo aPSCT because of rapid disease progression.
      Nineteen patients received both cycles of aPSCT, 8 progressed after cycle 1, 3
      refused the second cycle, and 1 died of fungal infection during cycle 1. Twelve
      patients remain relapse free at a median of 67 months from the initiation of
      therapy. Whereas the International Germ Cell Cancer Collaborative Group category
      at the time of initial diagnosis did not seem to predict outcome, the patient's
      probability of achieving durable remission was significantly associated with the
      Beyer prognostic score at the time of protocol entry. Regimens containing the
      most active agents in relapsed nonseminomatous germ cell tumors, including high
      dose paclitaxel, are well tolerated and have promising activity even in patients
      with poor-risk features who do not achieve durable remissions with standard
      therapy. The Beyer prognostic system is a valuable predictor for patients
      undergoing aPSCT.

PMID- 16275595
TI  - A meta-analytic review of surface electromyography among persons with low back
      pain and normal, healthy controls.
AB  - Significant differences in surface electromyography (SEMG) have been reported
      between persons with low back pain (LBP) and normal, healthy controls. This
      manuscript presents a systematic meta-analytic review of studies examining SEMG
      differences between these groups. Forty-four articles were identified using
      MEDLINE and a review of reference lists in articles. For static SEMG, the largest
      effect size was observed for SEMG while standing, with subjects having LBP
      demonstrating higher SEMG. The effect size for flexion/relaxation measures was
      found to be very high (d = -1.71). Studies examining SEMG during isometric
      exercise or muscle recovery following exercise produced inconsistent findings.
      Sensitivity and specificity of SEMG for dynamic SEMG measures averaged 88.8% and
      81.3%. Most classification schemes were statistically determined and utilized a
      combination of measures. Only one published study prospectively validated a
      classification scheme. SEMG measures of flexion-relaxation appear to distinguish
      LBP subjects from controls with good accuracy, and the sensitivity and
      specificity of SEMG can be increased by using multiple measures. Further research
      is needed to determine the combination of measures that are cost-effective,
      reliable, valid and discriminate with a high degree of accuracy between healthy
      persons and those with LBP. PERSPECTIVE: SEMG is a simple and noninvasive measure
      of muscle activity. SEMG measures hold promise as an objective marker of LBP.

PMID- 16275594
TI  - Hemolytic uremic syndrome after bone marrow transplantation: clinical
      characteristics and outcome in children.
AB  - Hemolytic uremic syndrome (HUS) is an uncommon but potentially life-threatening
      complication of hematopoietic stem cell transplantation. We retrospectively
      studied the medical records of 293 children who underwent allogeneic bone marrow
      transplantation at St. Jude Children's Research Hospital between 1992 and 1999 to
      describe the clinical course of and to identify risk factors for transplant
      associated HUS. Conditioning regimens included cyclophosphamide, cytarabine, and
      total body irradiation for patients with hematologic malignancies (n = 244);
      patients with nonmalignant diseases (n = 49) received disease-specific regimens.
      Grafts from unrelated or mismatched related donors were depleted of T
      lymphocytes, whereas matched sibling grafts were unmanipulated. All patients
      received cyclosporine as prophylaxis for graft-versus-host disease. Recipients of
      grafts from matched siblings also received pentoxifylline or short-course
      methotrexate. HUS developed in 28 (9.6%) patients at a median of 171 days after
      transplantation. We identified older donor age (P = .029), use of antithymocyte
      globulin in the conditioning regimen (P = .008), and recipient CMV seronegativity
      (P = .011) as being associated with an increased risk of HUS. With a multiple
      regression analysis, the use of antithymocyte globulin (beta = .86; P = .04) and
      recipient cytomegalovirus seronegativity (beta = .93; P = .035) remained
      significant risk factors for the development of HUS.

PMID- 16275596
TI  - Evaluation of reliability, validity, and preference for a pain intensity scale
      for use with the elderly.
AB  - The main objective of this research was to determine the initial psychometric
      properties of the Spanish Version of the Faces Pain Scale-Revised (FPS-R) as a
      measure of pain intensity for use with the elderly. To assess the scaling
      properties, validity, and reliability of the FPS-R, a total sample of 177
      subjects aged 65 years or older participated in this study. Ranking procedures,
      placement tasks, and test-retest methods were used. The participants were asked
      to rate their pain intensity by using the FPS-R and a pain thermometer (PT) and
      to inform about their affective state. They were also asked to imagine themselves
      in 5 hypothetical painful situations (Geriatric Painful Events Inventory) and
      rate the degree of pain by using the FPS-R and the PT at 2 different times. Rank
      ordering tasks for the individual faces showed excellent agreement between the
      expected ranking and the one provided by the participants (Kendall's W = 0.75, P
      < .0001). The pain intensity ratings reported with FPS-R and the PT were very
      similar, and the relationship between the intensity of pain experienced and
      participant's negative affective state was statistically significant (r = 0.32, P
      < .01). Test-retest correlations on the Geriatric Painful Events Inventory ranged
      from 0.44 to 0.7. All the participating subjects were asked to choose the pain
      scale they preferred. Our data suggest that, regardless of their age and/or
      gender, the subjects preferred the FPS-R to the PT. Overall, these results
      provide preliminary evidence of its reliability and convergent and criterion
      related validity as well as its strong ordinal properties with a sample of
      elderly subjects. PERSPECTIVE: This article presents the evaluation of
      reliability, validity, and preference for a pain intensity scale for use with the
      elderly, the Faces Pain Scale-Revised. This scale could help clinicians to assess
      the intensity of pain in cognitively intact elderly patients and might also be
      helpful in making decisions about treatment. Likewise, it could be used by
      researchers who wish to evaluate the effects of available treatments.

PMID- 16275597
TI  - Allodynia in relation to lesion site in central post-stroke pain.
AB  - Seventy-one percent of 122 patients with central post-stroke pain (CPSP) had
      allodynia that was tactile-, cold-, or movement-evoked. Site of thalamic (and
      some infratentorial) lesions as revealed by magnetic resonance imaging (MRI) was
      correlated in some cases with allodynia type and sensory perception threshold
      testing (QST). Notably, patients with cold allodynia tend to have more dorsally
      placed thalamic lesions than those without, and those with movement allodynia
      more anteriorly placed lesions. Suggestions are made for improved correlation.
      PERSPECTIVE: Only about half of patients with CPSP have allodynia (pain caused by
      innocuous stimulation); such stimulation is usually tactile- or cold-evoked or
      due to activation of stretch receptors (movement). We have found that, in some of
      our cases, the type of allodynia may depend on lesion location within the
      thalamus.

PMID- 16275598
TI  - Treatment response in antidepressant-naive postherpetic neuralgia patients:
      double-blind, randomized trial.
AB  - In 47 patients with postherpetic neuralgia (PHN) who had never had an adequate
      trial of any antidepressant, we performed a randomized, double-blind, parallel
      design trial comparing desipramine, amitriptyline, and fluoxetine. Patients were
      titrated to a maximum of 150 mg/day for desipramine and amitriptyline and 60
      mg/day for fluoxetine over a 3-week period and then treated for an additional 3
      weeks before tapering off study medication. A total of 38 subjects (81%)
      completed the entire trial. The modified intent-to-treat analysis of percent
      change in daily diary pain intensity scores showed no significant differences
      among the 3 drugs (ANOVA P = .120). Desipramine produced the greatest reduction
      in pain intensity (47%), followed by amitriptyline (38%) and fluoxetine (35%).
      Clinically meaningful pain relief (moderate or better) was significantly more
      likely with desipramine (12/15 patients) than with amitriptyline (9/17) or
      fluoxetine (5/15); chi(2)P = 0.036). The 11 subjects using opioids at study entry
      had smaller reductions in pain than those not using concomitant opioids. The
      fluoxetine group had the highest noncompletion rate (33%), with 1 subject
      hospitalized for hyponatremia. Although the magnitude of pain reduction and the
      category pain relief rating was not significantly different among the 3 drugs,
      the tricyclics desipramine and amitriptyline were well tolerated and provided
      clinically meaningful pain relief in 53% to 80% of subjects. PERSPECTIVE: Few
      clinical trials focus on patients who are naive to an entire class of medication.
      In this randomized blinded trial, the tricyclic antidepressants desipramine and
      amitriptyline were compared to the serotonin-selective antidepressant fluoxetine.
      All 3 drugs reduced PHN pain, with desipramine providing satisfactory relief in
      80% of those treated.

PMID- 16275599
TI  - A behavioral model of neuropathic pain induced by ligation of the common peroneal
      nerve in mice.
AB  - Different laboratory animal models of neuropathic pain that replicate
      pathophysiological changes in patients have been developed. In most animal models
      of neuropathic pain, both sensory and motor nerves are injured. Thus, animals
      usually show both abnormal sensory and motor responses. Assessment of the sensory
      system is likely to be affected by the motor defects, although motor functions
      have not been evaluated in previous neuropathic pain models. An ideal neuropathic
      pain model to assess behavioral nociceptive responses in animals is one without
      affecting motor function and without muscle injury. Here, we report a novel mouse
      model of neuropathic pain with normal motor functions. Ligation of the common
      peroneal nerve near the head of fibula was performed by a less invasive
      procedure. Long-lasting behavioral allodynia and thermal hyperalgesia was
      observed in mice after the ligation. Furthermore, behavioral allodynia is
      resistant to morphine treatment at 5 mg/kg body weight, as reported in some cases
      of neuropathic pain. Standard rotarod test analysis confirmed intact motor
      functions. Our results show that ligation of the common peroneal nerve can be
      used as an efficacious mouse model for assessing behavioral nociceptive responses
      in neuropathic pain. PERSPECTIVE: Tests to assess behavioral responses in a
      neuropathic pain model depend on intact motor functions. Here we report a less
      invasive procedure to ligate common peroneal nerve of leg to induce neuropathic
      pain with least motor defects.

PMID- 16275600
TI  - Activation of naloxone-sensitive and -insensitive inhibitory systems in a human
      pain model.
AB  - We investigated naloxone effects in a model of electrically induced pain and
      hyperalgesia. In a double-blind, placebo-controlled, cross-over study, 15
      volunteers underwent four 150-minute sessions of high-current-density electrical
      stimulation of their forearms. After 60 minutes, naloxone or placebo was given
      intravenously (increasing plasma concentrations of 0.1, 1, and 10 ng/mL; 30
      minutes each) in 3 of the 4 sessions. Pain ratings and areas of mechanical
      hyperalgesia were assessed at regular intervals during all sessions. The low
      doses of naloxone did not cause any significant change of pain rating of areas of
      hyperalgesia. In terms of intrasession effects, pain ratings and areas of
      hyperalgesia significantly decreased during the sessions to 62% (pain rating),
      70% (area of punctuate hyperalgesia), and 82% (area of allodynia) of the initial
      values. Naloxone (10 ng/ml) reversed these decreases. In terms of between-session
      effects, the time course of pain ratings remained constant from session to
      session. In contrast, the areas of punctate hyperalgesia successively decreased
      to 60% of initial value at the fourth repetition. The session effect was not
      reversed by naloxone. High-current-density electrical stimulation provokes
      central sensitization, but in addition inhibitory systems are activated that are
      only partly naloxone-sensitive. PERSPECTIVE: Endogenous inhibitory systems are of
      major importance for clinical pain conditions, but are not reflected in
      traditional human pain models. Here we show activation of a naloxone-sensitive
      short-term and a naloxone-insensitive long-term inhibitory system in a new model
      of electrically induced pain and hyperalgesia.

PMID- 16275601
TI  - Anger management style and associations with self-efficacy and pain in male
      veterans.
AB  - Despite the high prevalence of anger and maladaptive anger management among
      persons with chronic pain, the association between pain and anger has received
      little empirical attention. The purpose of the current study was to investigate
      the relationship between pain and anger management style and test for the
      hypothesized role of self-efficacy as a moderator of this association. Five
      hundred sixty-four veterans with chronic pain were administered measures of pain,
      self-efficacy, and anger management. As expected, the results demonstrated a
      significant positive relationship between pain intensity and maladaptive anger
      management and a significant negative association between self-efficacy and
      maladaptive anger. Furthermore, pain intensity and the interaction of self
      efficacy and pain intensity were significant predictors of maladaptive anger
      management. Surprisingly, patients reporting high self-efficacy and high pain
      intensity demonstrated more maladaptive anger management than individuals
      reporting high self-efficacy and low pain intensity. Patients reporting low self
      efficacy demonstrated high levels of maladaptive anger management, regardless of
      pain intensity level. PERSPECTIVE: Maladaptive anger management is associated
      with pain intensity and self-efficacy beliefs. Additional research is needed to
      explore the interaction of pain and self-efficacy and its impact on anger
      management.

PMID- 16275602
TI  - Analgesic efficacy of bradykinin B1 antagonists in a murine bone cancer pain
      model.
AB  - Cancer pain is a significant clinical problem because it is the first symptom of
      disease in 20% to 50% of all cancer patients, and 75% to 90% of patients with
      advanced or terminal cancer must cope with chronic pain syndromes related to
      failed treatment and/or tumor progression. One of the most difficult to treat
      cancer pains is metastatic invasion of the skeleton that can generate ongoing and
      bone breakthrough pain, which represents one of the most debilitating cancer
      related events. Because bradykinin has been shown to be released in response to
      tissue injury and plays a significant role in driving acute and chronic
      inflammatory pain, we focused on bradykinin antagonists in a model of bone cancer
      pain. In our model of bone cancer, which involves the injection and confinement
      of 2472 sarcoma cells to the mouse femur, pharmacologic blockade of the
      bradykinin B1 receptor is effective in reducing pain-related behaviors at both
      early and advanced stages of bone cancer. PERSPECTIVE: Bone cancer pain can be
      severe and difficult to control fully. With a mouse model of bone cancer pain we
      demonstrate that pharmacologic blockade of the bradykinin B1 receptor is
      effective in reducing bone cancer pain-related behaviors, suggesting that B1
      antagonists might be useful in attenuating bone cancer pain in humans.

PMID- 16275604
TI  - Clinical and angiographic follow-up in patients with Cypher or Taxus stents in
      populations with high percentage of trial-excluded lesions.
AB  - BACKGROUND: Drug-eluting stents (DESs) are being used in real life in patients
      with complex lesions usually excluded from the published trials. It is reasonable
      to think that the results could be worse, and the performance may be different
      between DES when these complex lesions are included. METHODS AND MATERIAL: To
      investigate this issue, we studied our first 82 patients with DES (54 patients
      with Cypher (C) and 28 patients with Taxus (T) (129 lesions, with 1.57 lesions
      per patient). Seventy-one complex lesions were treated with C stent, 41 with T
      stent, and 17 with no DES. It was a high-risk population, as reflected by 64%
      unstable angina and 40% diabetes mellitus. Of the 112 DES complex lesions
      treated, 38% would have been excluded from the Sirius and Taxus IV trials.
      RESULTS: The main data on intra-segment angiographic measures showed a late
      luminal loss lower for the C stent than for the T stent (0.17+/-0.45 and 0.44+/
      0.6, P=.02, respectively). The restenosis and target lesion revascularization
      percentages were also lower for the C stent (8.4% vs. 24.4%, P=.07 and 5.6% vs.
      17.1%, P<.05, respectively). In the complex lesions without restenosis, 28% would
      have been excluded from the trials, while in complex lesions with restenosis,
      there were 53% (P=.05) (with a homogeneous percentage between the C and T
      groups). The predictor variables of restenosis in the 112 DES-treated complex
      lesions were length (P=.03, IC=0.97-1.6) and the pre-reference diameter (P=.06).
      CONCLUSIONS: In our experience, the C stent is superior to the T stent when
      treating populations with a high percentage of complex lesions excluded from the
      trials.

PMID- 16275605
TI  - One-year follow-up of transcoronary sinus administration of autologous bone
      marrow in patients with chronic refractory angina.
AB  - PURPOSE: Based on our preclinic studies with autologous unfractionated bone
      marrow (AUBM) via coronary sinus with transitory occlusion, a clinic study in
      patients with chronic refractory angina was designed. The objectives were to
      evaluate tolerance of the procedure, safety, and feasibility with 1 year follow
      up. METHODS AND MATERIALS: Clinical study with inclusion and exclusion criteria
      defined by an Independent Clinical Committee was carried out. Fifteen patients
      underwent transcoronary sinus administration with a 15-min occlusion of freshly
      aspirated and filtered AUBM (60-120 ml). Feasibility was evaluated with Seattle
      Angina Questionnaire (SAQ), Canadian Cardiovascular Society (CCS) angina
      classification, perfusion dipyridamole, and coronary angiography. RESULTS: There
      were no changes in the tolerance parameters. There were no deaths or myocardial
      infarction during the follow-up. Three patients were readmitted into the
      hospital. During the follow-up, one patient was diagnosed with cancer of the
      lung. Improvement of 30% in the quality of life was evaluated by SAQ. The CCS
      angina classification showed that the mean angina class was 3.0+/-0.53 at
      baseline, which improved to 1.6+/-0.63 at 1 year (P<.001). Perfusion imaging
      (core lab) showed improvement in 12 of 15 patients, with a mean improvement of
      40.9% at rest (22 vs. 13) (P<.01) and 45.3% at stress (26.5 vs. 14.5) (P<.05).
      Coronary angiography showed more collateral vessels in 10 of 15 patients.
      CONCLUSIONS: We can conclude that AUBM via coronary sinus is feasible in patients
      with chronic refractory angina after 1 year follow-up, and it appears to be safe.

PMID- 16275607
TI  - A clinically relevant large-animal model for evaluation of tissue-engineered
      cardiac surgical patch materials.
AB  - Extracellular matrix (ECM) scaffolds may be useful as a tissue engineering
      approach toward myocardial regeneration in the infarcted heart. An appropriate
      large-animal model for testing the utility of biologically derived ECM in this
      application is needed. The purpose of this study was to develop such a model for
      optimal procedural success during and after patch implantation surgery.
      Myocardial infarction (MI) was created by embolization of the diagonal artery
      (DA) branch of the left anterior descending coronary artery with collagen
      suspension. After 4 to 6 weeks, 14 pigs received patch implant (ECM or expanded
      polytetrafluoroethylene). Six pigs were infarcted in the first DA and seven pigs
      in the second DA. Electrophysiology study was performed within 3 days before
      surgery. During surgery, the size and location of the infarct were measured.
      Infarcted myocardium (1.5-cm diameter) was transmurally excised under partial
      cardiopulmonary bypass. Patches (3-cm diameter) were sutured to the
      endomyocardial defect. Four pigs died postoperatively. After 1 month, 10 pigs
      were euthanized and the locations of patches were examined. Success rate of patch
      implant in the second DA (85.7%) was higher than the first DA (50%) group.
      Infarct size in the second DA was smaller than in the first DA (4.6+/-1.2 vs.
      10.8+/-2.4 cm(2), P<.05). The second DA was more anteriorly positioned, which
      enabled easier access from the midsternal thoracotomy. However, the first DA was
      more laterally located requiring more manipulation of the heart during surgery.
      Electrophysiology revealed no ventricular tachyarrhythmia in the second DA but
      33.3% in the first DA group (P<.05). At necropsy, the endocardial position of the
      first DA-infarct patches was anteroapical, whereas the second DA-infarct patches
      were more basolateral and often involved the anterior papillary muscle. The
      success rate of patch implant was associated with infarction size and location,
      and may be related to arrhythmic substrate. Experimental MI created by the second
      DA embolization is a feasible model for investigation of tissue-engineered
      cardiac patch implantation. This large-animal model is also suitable for study of
      cell therapy via endocardial catheter-based approaches or open surgical methods.

PMID- 16275606
TI  - Optimizing dosimetry with high-dose intracoronary gamma radiation (21 Gy) for
      patients with diffuse in-stent restenosis.
AB  - BACKGROUND: The efficacy of intracoronary gamma radiation (IRT-gamma) in reducing
      recurrent in-stent restenosis (ISR) is well established using doses of 14-18 Gy.
      We sought to examine whether an escalation in dose to 21 Gy is safe and confers
      additional benefit in reducing repeat revascularization and major adverse cardiac
      events (MACE) in patients with diffuse ISR. METHODS: Forty-seven patients with
      diffuse ISR (lesion length 20-80 mm) in native coronary arteries (n=25) and
      saphenous vein grafts (n=22) underwent percutaneous transluminal coronary
      angioplasty and/or additional stents followed by IRT-gamma using the Checkmate
      system (Cordis) with a dose of 21 Gy. All patients were discharged with
      clopidogrel for 12 months and aspirin indefinitely. Six-month angiographic and 12
      month clinical outcomes of these patients were compared to 120 patients treated
      with 18 Gy using the same system. RESULTS: At baseline, patients in the 21-Gy
      group had more multivessel, vein graft disease and history of prior myocardial
      infarctions and coronary artery bypass grafts (P<.001). The use of debulking
      devices and stents was less in this group (P<.001). Procedural and in-hospital
      complications were similar. Follow-up at 6 months revealed nonsignificant but
      lower late loss (in-stent, 0.33+/-0.7 mm; in-lesion, 0.41+/-0.6 mm) in the 21-Gy
      group compared to the 18-Gy group; follow-up at 12 months revealed a trend toward
      less overall myocardial infarction, although repeat revascularization and MACE
      rates were similar. CONCLUSIONS: IRT-gamma therapy for diffuse ISR lesions with a
      21-Gy dose is clinically safe and feasible with marked reduction in late loss but
      does not confer additional benefit with regard to repeat revascularization and
      MACE when compared to a dose of 18 Gy.

PMID- 16275608
TI  - A novel method for safe and accurate left anterior descending coronary artery
      ligation for research in rats.
AB  - BACKGROUND: Left anterior descending artery (LAD) ligation has been commonly used
      in rats to induce left ventricular infarction for research purposes. However, LAD
      ligation is a very difficult procedure with high mortality rate in rats. We have
      developed a safe method of LAD ligation in rats with low mortality. METHODS:
      Thirty-six Sprague-Dawley male rats weighing 300-350 g were selected for LAD
      ligation for the induction of ischemic cardiomyopathy. The surgery was performed
      under general anesthesia. Left-sided thoracotomy was performed by cutting the
      fifth and sixth ribs. The pericardium was opened, and the heart exteriorized with
      a cardiac holder consisting of a plastic loop (1.5x2 cm). The LAD was localized 1
      2 mm below the junction of pulmonary conus and the left atrial appendage. A 5.0
      silk suture was used to ligate the LAD from the left border of the pulmonary
      conus to the right border of the left atrial appendage. The heart was returned
      back to the chest and the chest wall closed with presutured lopes of 4.0 silk.
      RESULTS: Mid-LAD ligation was successful in all rats, with less than 5%
      mortality. The entire surgery was performed in less than 15 min. This method is
      simple and can be learned in a short period of time. Rats survived the procedure
      with induction of congestive heart failure for up to 3 weeks of follow-up.
      CONCLUSIONS: Using our method, LAD ligation can safely be performed in rats 1-2
      mm below the junction of the pulmonary conus and the left atrial appendage, with
      a very low mortality rate.

PMID- 16275609
TI  - Immunosuppression against restenosis. Efficacy of a radiofrequency guidewire and
      oral prednisone in achieving and maintaining coronary artery patency after
      stenting.

PMID- 16275610
TI  - The no-flow phenomenon during diagnostic coronary angiography.
AB  - OBJECTIVES: Slow flow of dye in epicardial coronary arteries is not an infrequent
      finding in patients during routine coronary angiography. The extreme form of this
      phenomenon, namely, no flow or Thrombolysis in Myocardial Infarction (TIMI) 0-1,
      is very uncommon with life-threatening consequences. We consider the present
      report as the first one, to our knowledge, that describes this angiographic
      entity and how prompt recognition and adequate management prevent certain death
      in this population. DESIGN, SETTING, AND PATIENTS: Retrospective review of the
      cardiac catheterization laboratory database at our medical center. Out of 5700
      cardiac catheterizations performed by the authors during the past 5 years, 10
      cases (0.17%) were identified as having no flow or very slow flow during their
      routine diagnostic coronary angiogram. CASE ANALYSIS: The no-flow phenomenon
      occurred during the first coronary injection in the left coronary system. We
      specifically emphasize that none of these cases was a consequence of inadvertent
      air injection, vasospasm, or coronary dissection. In 80% of our cases, flow was
      completely absent (TIMI 0), and in two cases (20%) it was very slow and never
      filling the distal vessel (TIMI 1). Despite immediate recognition and prompt
      maneuvers and treatment with intracoronary vasodilator administration, 60% of
      these patients progressed to full cardiopulmonary arrest with all of them having
      extended cardiopulmonary resuscitation (CPR) and pharmacological treatment. Only
      one patient required intra-aortic balloon pump (IABP) support and temporary
      pacemaker. All patients recovered completely with no clinical consequences.
      Characteristics of patients with this complication are described, and several
      possible etiologies are analyzed. CONCLUSIONS: Definite conclusions for the
      reason of the no-flow phenomenon are not possible at present, despite multiple
      different theories that could explain it. What is important from the clinical
      standpoint is that, although rare, it is a potentially life-threatening condition
      during diagnostic coronary angiography that should be recognized and aggressively
      treated. We consider the present report as the first one, to our knowledge, that
      describes this angiographic entity, and how prompt recognition and adequate
      management prevents certain death in this population.

PMID- 16275611
TI  - Ultrasound assessment of internal carotid disease candidates to endovascular
      carotid stenting and cardiac surgery is inaccurate in patients with severe aortic
      valve stenosis.
AB  - PURPOSE: The association of internal carotid artery disease (ICAD) with aortic
      valve stenosis (AVS) constitutes a very high-risk clinical occurrence in which
      combined surgery may increase the operative risks and carotid stenting before or
      after cardiac surgery may be a valuable option. Unfortunately, in patients with
      AVS, the evaluation of carotid arteries by Doppler ultrasound (DUS) may be
      inaccurate. The present retrospective study is aimed to evaluate the pitfalls of
      DUS and the role of carotid angiography before carotid stenting in evaluating
      ICAD in patients with AVS. METHODS: We analyzed the clinical, hemodynamic, and
      angiographic findings of 200 patients with moderate to severe AVS (5.5% of 3600
      patients underwent cardiac catheterization; mean age, 68.5+/-10.6 years)
      investigated in our institution over the past 2 years. Patients with moderate to
      severe AVS, candidates to open cardiac surgery, underwent carotid ultrasonography
      to assess ICAD and complete left and right catheterization with coronary artery
      angiography, and in case of doubtful carotid artery sonography, the patients
      underwent also carotid artery angiography at the time of complete cardiac
      catheterization before confirming the indication to carotid stenting or combined
      surgery. RESULTS: Seventy patients with moderate to severe AVS and doubtful
      carotid ultrasonography underwent coincident carotid angiography. Reasons for
      suboptimal Doppler ultrasonographic examination are related to the anatomical or
      to the difficult evaluation of Doppler flow due to hemodynamic influences of AVS.
      On carotid angiography, 20 patients (28.5%, male/female, 8/12; mean age, 72.1+/
      5.1 years) were diagnosed to have critical stenosis of one (16 patients) or both
      (4 patients) internal carotid arteries; in five patients, a significant ICAD was
      not diagnosed by DUS, whereas in seven patients, the stenosis was underestimated
      by DUS (mean luminal narrowing, 58+/-12.7% vs. 76.7+/-19.3%, P<.03), and in the
      other eight patients, DUS overestimated ICAD (77+/-12% vs. 62+/- 13.4%, P<.02).
      Out of this group, six patients underwent successful carotid stenting, six
      combined surgical treatments, and eight underwent simple cardiac surgery.
      CONCLUSIONS: Doppler ultrasound may be inconclusive in evaluating ICAD in
      patients with moderate to severe AVS candidates to cardiac surgery and
      endovascular carotid stenting. Carotid angiography may be proposed at the time of
      cardiac catheterization in patients with inconclusive DUS examination.

PMID- 16275612
TI  - An uncommon coronary artery fistula.

PMID- 16275613
TI  - Immunomodulatory and therapeutic properties of the Nigella sativa L. seed.
AB  - A larger number of medicinal plants and their purified constituents have been
      shown beneficial therapeutic potentials. Seeds of Nigella sativa, a dicotyledon
      of the Ranunculaceae family, have been employed for thousands of years as a spice
      and food preservative. The oil and seed constituents, in particular thymoquinine
      (TQ), have shown potential medicinal properties in traditional medicine. In view
      of the recent literature, this article lists and discusses different
      immunomodulatory and immunotherapeutic potentials for the crude oil of N. sativa
      seeds and its active ingredients. The published findings provide clear evidence
      that both the oil and its active ingredients, in particular TQ, possess
      reproducible anti-oxidant effects through enhancing the oxidant scavenger system,
      which as a consequence lead to antitoxic effects induced by several insults. The
      oil and TQ have shown also potent anti-inflammatory effects on several
      inflammation-based models including experimental encephalomyelitis, colitis,
      peritonitis, oedama, and arthritis through suppression of the inflammatory
      mediators prostaglandins and leukotriens. The oil and certain active ingredients
      showed beneficial immunomodulatory properties, augmenting the T cell- and natural
      killer cell-mediated immune responses. Most importantly, both the oil and its
      active ingredients expressed anti-microbial and anti-tumor properties toward
      different microbes and cancers. Coupling these beneficial effects with its use in
      folk medicine, N. sativa seed is a promising source for active ingredients that
      would be with potential therapeutic modalities in different clinical settings.
      The efficacy of the active ingredients, however, should be measured by the nature
      of the disease. Given their potent immunomodulatory effects, further studies are
      urgently required to explore bystander effects of TQ on the professional antigen
      presenting cells, including macrophages and dendritic cells, as well as its
      modulatory effects upon Th1- and Th2-mediated inflammatory immune diseases.
      Ultimately, results emerging from such studies will substantially improve the
      immunotherapeutic application of TQ in clinical settings.

PMID- 16275614
TI  - The immunopharmacological properties of transforming growth factor beta.
AB  - Transforming growth factor-beta (TGF-beta) family members are multifunctional
      molecules, which play pivotal roles in regulating cell proliferation,
      differentiation, migration, development, tissue remodeling and repair. These
      events are closely associated with host immune responses and inflammation.
      Despite some controversies on their function in controlling dendritic and T
      regulatory cell development and activity, the importance of TGF-betas in the
      progress of autoimmunity and inflammatory diseases has been well appreciated and
      new aspects of their contribution continue to be recognized. Since one of the
      major biological properties of TGF-betas is its capacity to potently suppress
      immune responses, they are considered as candidates for the development of
      therapeutic agents to fend off undesirable damage associated with immune and
      inflammatory conditions.

PMID- 16275615
TI  - Macrophage immunomodulatory activity of polysaccharides isolated from Juniperus
      scopolorum.
AB  - Extracts of cones and leaves of different species of the genus Juniperus have
      been used for centuries to treat a variety of medical problems; however, little
      is known about the active components conferring therapeutic properties to these
      extracts. To address this issue, we extracted water-soluble polysaccharides from
      Juniperus scopolorum cones and used ion exchange and size exclusion
      chromatography to separate them into five fractions, with estimated Mr of 30, 60,
      100, 200, and 680 kDa, respectively. All fractions contained type II
      arabinogalactan in their structure, as determined by reaction with Yariv reagent
      and structural analysis by proton nuclear magnetic resonance spectroscopy, but
      lacked complement fixing activity. Analysis of the effects of Juniper
      polysaccharides on murine peritoneal macrophages, cultured J774.A1 macrophages,
      and human mononuclear phagocytes demonstrated that the high molecular weight
      polysaccharide fractions (200 and 680 kDa) had potent immunomodulatory activity.
      These polysaccharide fractions primed macrophages for an enhanced respiratory
      burst, directly stimulated NO production via induction of nitric oxide synthase,
      and induced macrophages to secrete both inflammatory (IL-1, IL-6, TNF-alpha, and
      IL-12) and anti-inflammatory (IL-10) cytokines. These data suggest that at least
      part of the beneficial therapeutic effects reported for extracts of juniper cones
      are due to modulation of monocyte/macrophage immune functions.

PMID- 16275616
TI  - Desloratadine and levocetirizine improve nasal symptoms, airflow, and allergic
      inflammation in patients with perennial allergic rhinitis: a pilot study.
AB  - BACKGROUND: Nasal obstruction is the main symptom in patients with perennial
      allergic rhinitis. Some new antihistamines have been demonstrated to be capable
      of improving this symptom. OBJECTIVE: The aim of this pilot study was to evaluate
      nasal symptoms, nasal airflow, eosinophils, and IL-4 in patients with perennial
      allergic rhinitis, before and after treatment with two new antihistamines:
      desloratadine and levocetirizine. METHODS: Thirty patients with perennial
      allergic rhinitis were evaluated, 26 males and 4 females (mean age 26+/-7.1
      years). All of them received either desloratadine (5 mg/daily) or levocetirizine
      (5 mg/daily) or placebo for 4 weeks. The study was double-blind, parallel-group,
      placebo-controlled, and randomized. Total symptom score (including: rhinorrhea,
      nasal itching, sneezing, and nasal obstruction) was assessed before and after
      treatment. Rhinomanometry and decongestion test, nasal lavage, and nasal scraping
      were performed in all subjects before and after treatment. Eosinophils were
      counted by conventional staining; IL-4 was measured by immunoassay of fluids
      recovered from nasal lavage. RESULTS: Desloratadine and levocetirizine treatment
      induced significant symptom relief and significant reduction of IL-4. Both
      antihistamines significantly affected all parameters in comparison with placebo.
      CONCLUSIONS: This pilot study demonstrates the effectiveness of antihistaminic
      treatment in: i) relieving nasal symptoms, including obstruction, ii) improving
      nasal airflow, iii) exerting decongestant activity, iv) reducing eosinophil
      infiltration, and v) diminishing IL-4 levels.

PMID- 16275617
TI  - A fetal sheep liver extract containing immunostimulatory substances including LPS
      acts as leukocyte activator in cells of LPS responder and non responder mice.
AB  - Purified fractions from a fetal sheep liver extract (FSLE) were investigated, in
      a murine model, for induction of leukocyte stimulating activities. The fractions
      FSLE-1 and FSLE-2 induced splenocyte proliferation in vitro in C57Bl/10ScSn (LPS
      responder) mice comparable to LPS, and in C57Bl/10ScCr (LPS non responder) mice.
      They also stimulated the release of nitrogen radicals in bone marrow-derived
      macrophages (BMDM) from several mouse inbred strains including both C57Bl/10ScSn
      and C57Bl/10ScCr mice. Stimulation of NO production could be blocked by L-NMMA,
      an inhibitor of iNOS, and enhanced by the simultaneous addition of IFN-gamma.
      Moreover, stimulation of macrophages by FSLE-1 and FSLE-2 induced a cytostatic
      effect of the activated macrophages for Abelson 8-1 tumor cells. The stimulatory
      activity of the purified fractions is partially due to trace amounts of LPS
      derived from the fetal liver extract which was enriched during purification. Our
      results may help to explain the beneficial effect of the extract in patients
      which has been observed clinically.

PMID- 16275618
TI  - The anti-anaphylactic effect of the gall of Rhus javanica is mediated through
      inhibition of histamine release and inflammatory cytokine secretion.
AB  - The immediate-type allergic reaction (anaphylaxis) is involved in many allergic
      diseases such as asthma, allergic rhinitis and sinusitis. We investigated the
      effect of the gall of Rhus javanica (GRJ) on the model of the immediate-type
      allergic reaction, and studied its possible mechanisms. GRJ inhibited compound
      48/80-induced systemic reactions in mice. GRJ attenuated immunoglobulin (Ig) E
      mediated local allergic reactions. In addition, GRJ dose dependently decreased
      histamine release from rat peritoneal mast cells activated by compound 48/80 or
      IgE. The decreasing effect of GRJ on the histamine release was mediated by the
      modulation of cAMP and [Ca2+]i in mast cells. Furthermore, GRJ decreased the
      phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated TNF
      alpha and IL-6 secretion in human mast cells. The inhibitory effect of GRJ on the
      pro-inflammatory cytokine was c-Jun N-terminal kinase and nuclear factor-kappaB
      dependent. Our findings provide evidence that GRJ inhibits mast cell-derived
      immediate-type allergic reactions, and suggest the possible mechanisms of action.

PMID- 16275619
TI  - All-trans-retinoic acid accelerates the differentiation of human B lymphocytes
      maturing into plasma cells.
AB  - There is a growing body of evidences suggesting the important role of vitamin A
      for the optimal maintenance and functioning of immune system. It is now well
      established that retinoic acid (RA), a product of oxidative metabolism of vitamin
      A, is the most active vitamin A derivative physiologically. In this study, we
      examined the role of RA in B cell maturation in T cell-dependent activation
      pathway. RA enhanced the immunoglobulin synthesis by tonsillar B cells in anti
      CD40 plus IL-10-mediated culture system. When the kinetics of B cells with
      different phenotypic characteristics were monitored during 9 days culture period
      by flow cytometric analysis, it displayed the increase of the B cells with plasma
      cell phenotype (CD38+/CD20-/IgD-) in the presence of RA. As resting B cells from
      tonsil expressed mRNA of the RA receptors alpha, beta, gamma and RXRalpha by
      reverse transcriptase-polymerase chain reaction, it is certain that RA effect is
      mediated by RA receptors. Taken together, this study showed that retinoic acid
      could accelerate the differentiation of B cells maturing into antibody producing
      cells.

PMID- 16275620
TI  - Impaired function of hepatic natural killer cells from murine chronic HBsAg
      carriers.
AB  - In the present study, we demonstrated hepatic NK cells in murine chronic HBsAg
      carriers for the first time. It was found that the number of hepatic NK cells was
      decreased; natural activation of hepatic NK cells was declined; and cytotoxicity
      of hepatic NK cells was attenuated, which might relate to the down-regulated
      expression of TRAIL on hepatic NK cells. Additionally, the response of hepatic NK
      cells to the specific stimulation of Poly (I:C) in murine chronic HBsAg carriers
      was changed. The increase in anti-tumor cytotoxic activity of intrahepatic
      activated NK cells was markedly impaired in the transgenic mice. The transgenic
      mice used here had high incidence of hepatocellular carcinoma, which might result
      from the relative weak reactivity and impaired anti-tumor activity of NK cells in
      the liver. Furthermore, remarkable liver injury was observed after stimulation of
      Poly (I:C), demonstrating the hypersensitivity to Poly (I:C) of murine chronic
      HBsAg carriers which might be related to the accumulated NK cells in the liver.
      Why the murine chronic HBsAg carriers are characterized with impaired hepatic NK
      cells and the implication of the impaired hepatic NK cells in pathogenesis of HBV
      related diseases, such as hepatocellular carcinoma and recrudescent hepatitis, is
      worth of further investigating. These results of the functions of hepatic NK
      cells in murine chronic HBsAg carriers would contribute to interpreting the
      immune responses of NK cells in the liver and the immunological mechanisms of
      liver diseases in human chronic HBsAg carriers.

PMID- 16275621
TI  - Differential effect of sodium arsenite during the activation of human CD4+ and
      CD8+ T lymphocytes.
AB  - Contamination of water with arsenic is a problem affecting several regions of the
      world. Peripheral blood mononuclear cells (PBMC) from chronically exposed
      individuals show a lower replicating activity than non-exposed individuals when
      stimulated with phytohemagglutinin (PHA). We have previously reported that PBMC
      from healthy donors treated in vitro with 1 muM sodium arsenite (NaAsO2) and
      stimulated with PHA showed a reduction in proliferation by a delay in cell cycle
      entry and a decrease in the rounds of cell division. In this paper we tested the
      effect of 1-5 muM NaAsO2 on the proliferation, viability, blast transformation,
      expression of the CD4 and CD8 molecules, and during the activation and
      proliferation of both CD4+ and CD8+ T lymphocytes. We found a reduction in cell
      proliferation and an increase in non-dividing cells with higher concentrations of
      NaAsO2 (2-5 microM) when proliferation was studied by 5,6-carboxyfluorescein
      diacetate succinimidyl ester (CFSE) dilution. The use of 7-aminoactinomycin D (7
      AAD) in CFSE-labeled cells allowed us to detect an increase in percentage of non
      dividing cells, and an increase in apoptotic/dead cells mainly in non
      proliferating cells. Analysis of the expression of CD4 and CD8 molecules on these
      cells showed that concentrations > or = 2 microM NaAsO2 reduced the expression of
      the CD8 molecule and induced apoptosis/death in CD4+ cells. Analysis of blast
      transformation by flow cytometry showed an accumulation of CD8+ resting cells in
      the presence of NaAsO2. Analysis of CD25 and CD69 expression in kinetics
      experiments in both subtypes showed a delay in the expression of CD25 and a delay
      in the downregulation of the CD69 molecule, in both CD4+ and CD8+ cells. However,
      in the case of CD8+ cells, we detected an accumulation of a CD25- CD69-
      population in the presence of increasing concentrations of NaAsO2. Altogether,
      our results show that NaAsO2 alters the expression kinetics of the early
      activation molecules CD25 and CD69 similarly in both subtypes. In addition,
      activated and non-activated CD4+ cells die by apoptotic mechanisms and although a
      percentage of CD8+ cells also die by apoptosis, a subpopulation of these cells is
      unable to activate and thus accumulates as resting cells.

PMID- 16275622
TI  - Blockade of p38 map kinase inhibits complement-induced acute lung injury in a
      murine model.
AB  - Features of acute lung injury include neutrophil influx and increased vascular
      permeability with resultant pulmonary edema. Inhibition of p38 mitogen-activated
      protein kinase (MAPK) in in vivo models of endotoxin-induced inflammation results
      in reduction of organ injury as well as symptomatic relief. In this study, mice
      received an oral dose (100 mg/kg) of the p38 MAPK inhibitor, SB203580, followed
      by intratracheal instillation of an agent of complement origin, C5a des arg, at a
      concentration (10 microg) that induced acute lung injury. Neutrophil and protein
      content of bronchoalveolar lavage fluid as indicators of leukocyte influx and
      vascular permeability respectively were assessed. Animals that received C5a
      instillation had a significant influx of neutrophils into the lungs (49+/-8%)
      while mice receiving C5a-instillation and prior treatment with SB203580 exhibited
      diminished influx (16+/-5%). Similarly, pretreatment with oral SB203580 resulted
      in decreased vascular permeability (241+/-34 microg/ml) than the positive control
      animals (407+/-135 microg/ml). Activity analysis of total lung p38 MAPK revealed
      that p38 activity was increased at 4 h after C5a-instillation and that SB203580
      treated C5a-instilled mouse lungs had lower p38 activity than did the C5a
      instilled control. These data indicate that oral administration of an agent
      inhibitory for p38 MAPK offers a protective effect in the lungs from both
      neutrophil influx and protein leak associated with acute lung injury.

PMID- 16275623
TI  - Zidovudine plus sulfamethoxazole-trimethoprim adversely affects B lymphocyte
      maturation in bone marrow of normal mice.
AB  - Sulfamethoxazole-trimethoprim and zidovudine (AZT), drugs used often in
      combination in patients infected with HIV, were investigated for their effects on
      B cell development in a mouse model. BALB/c mice were randomized to receive oral
      doses of AZT, sulfamethoxazole-trimethoprim, or the combination via oral gavage
      for up to 28 days. Immune cell populations in the spleen, lung, and peripheral
      blood were examined, and toxicity to B lineage subtypes in the bone marrow was
      investigated by phenotypic analysis via flow cytometry. Pre-pro-B, pro-B, early
      pre-B, and late pre-B cells were assayed for apoptosis and analyzed for cell
      cycle profile. Total as well as B cell splenic and bone marrow cellularities were
      significantly decreased by using the drugs concomitantly, while B cell
      populations in the lungs and percentage in the peripheral blood were not
      affected. Combination therapy caused significant increases in apoptosis in B
      cells and granulocytes in the bone marrow, with the late pre-B cell population
      being the most depleted. The proliferative expansion and differentiation of early
      pre-B cells (B220+/CD43+/BP-1+/HSA+) to the late pre-B cell (B220+/CD43-/IgM-)
      stage was blocked, with early pre-B cells accumulating in the proliferative
      phases of the cell cycle. This apoptosis increase is likely due to elevated blood
      sulfamethoxazole concentrations that were observed in mice also receiving AZT.
      Concurrent sub-chronic administration of AZT and sulfamethoxazole-trimethoprim
      adversely affected B lymphocyte development in mouse bone marrow.

PMID- 16275624
TI  - (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide analog mediates
      immunosuppressive effects in vitro and in vivo.
AB  - A series of triptolide analogs have been successfully synthesized. In the present
      study we demonstrated one of them, (5R)-5-hydroxytriptolide (LLDT-8), showed low
      cytotoxicity and relative high immunosuppressive activities as compared with its
      parent compound triptolide in vitro. The CC50 values of triptolide and LLDT-8
      were 2.1+/-0.3 and 256.6+/-73.8 nM, respectively. LLDT-8 significantly inhibited
      the proliferation of splenocytes induced by concanavalin A (ConA),
      lipopolysaccharide (LPS), or mixed lymphocyte reaction (MLR), and the IC50 values
      were 131.7+/-32.4, 171.5+/-17.3, and 38.8+/-5.1 nM, respectively. LLDT-8 (25, 50,
      100 nM) dose-dependently reduced the production of Th1 type cytokines (IFN-gamma,
      IL-2) and inflammatory cytokines (TNF-alpha, IL-6) in vitro. Administration of
      LLDT-8 (at the low dose of 0.4 microg/kg, i.p.; 40 microg/kg, p.o.) intensively
      suppressed 2,4-dinitrofluorobenzene (DNFB)-induced delayed type hypersensitivity
      (DTH) reactions. Treatment with LLDT-8 (40 microg/kg, i.p. and p.o.) also
      markedly inhibited the sheep red blood cell (SRBC)-induced antibody production in
      BLAB/c mice. Most importantly, comparing with triptolide, LLDT-8 significantly
      reduced toxicity, with a 122-fold lower cytotoxicity in vitro and 10-fold lower
      acute toxicity in vivo. The results suggested that LLDT-8 had immunosuppressive
      activities in both cellular and humoral immune responses. LLDT-8 might be a
      potential therapeutic agent for immune-related diseases.

PMID- 16275625
TI  - Prevention of graft-versus-host disease by a novel immunosuppressant, (5R)-5
      hydroxytriptolide (LLDT-8), through expansion of regulatory T cells.
AB  - (5R)-5-hydroxytriptolide (LLDT-8) is a new compound derived from triptolide,
      which is the major immunosuppressive fraction of Tripterygium wilfordii Hook. F
      (TWHF). In this study, we demonstrated that administration of LLDT-8 (1
      mg/kg/day, p.o.) effectively prevented weight loss and death induced by allo-BMT
      (BLAB/c, H-2d to C57BL/6, H-2b), and extended survival in allo-BMT model of
      aGVHD. Following days 7 to 28 after allo-BMT, the allogeneic graft survived by
      increasing the number of engrafted cells (H-2d) in spleens of recipient mice with
      LLDT-8 treatment. To construe the immunosuppressive effects of LLDT-8, the
      splenocytes (H-2d) of LLDT-8 treated recipients (H-2b) were tested for the
      proliferative responses to donor antigen (H-2d), host antigen (H-2b) and mitogen
      (ConA) stimulations, respectively, the results indicated that LLDT-8 induced the
      T cells' unresponsiveness to donor and host antigens, while still maintaining
      response to ConA; Compared with the vehicle group of GVHD mice, administration of
      LLDT-8 significantly inhibited T cells to produce IFN-gamma with or without host
      antigen or ConA stimulation. Further studies indicated LLDT-8 had a normalizing
      effect on the ratio of CD4+/CD8+ T cells, and increased CD4+CD25+ T regulatory
      cells with the Foxp3 expression in splenocytes from LLDT-8 treated mice. The
      results outline the great potential of LLDT-8 as a therapeutic tool to induce
      suppression in GVHD.

PMID- 16275626
TI  - Anti-inflammatory potential of Antrodia Camphorata through inhibition of iNOS,
      COX-2 and cytokines via the NF-kappaB pathway.
AB  - Antrodia camphorata (A. camphorata), well known in Taiwan as a traditional
      Chinese medicine, has been shown to exhibit antioxidant and anticancer effects.
      In the present study, therefore, we have examined the effects of the fermented
      culture broth of A. camphorata (25-100 microg/ml) in terms of lipopolysaccharide
      (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production, and
      inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein
      expression in RAW 264.7 macrophages. Our results indicate concentration-dependent
      A. camphorata inhibition of LPS-induced NO and PGE2 production, without
      appreciable cytotoxicity on the RAW 264.7 cells. A. camphorata also attenuates
      the production of LPS-induced tumor necrosis factor (TNF-alpha) and interleukin
      (IL)-1beta. Furthermore, A. camphorata blocks the IkappaB-alpha degradation
      induced by LPS. These results indicate that A. camphorata inhibits LPS induction
      of cytokine, iNOS and COX-2 expression by blocking NF-kappaB activation.
      Therefore, we report the first confirmation of the anti-inflammatory potential of
      this traditionally employed herbal medicine in vitro.

PMID- 16275627
TI  - Chlorophyllin attenuates IFN-gamma expression in lipopolysaccharide-stimulated
      murine splenic mononuclear cells via suppressing IL-12 production.
AB  - Chlorophyllin (CHL) is a chlorophyll derivative with anticarcinogen and
      antioxidant activities. Despite clinical importance of CHL as a potential
      therapeutics for treating cancer patients, little is known about the
      immunological properties of CHL. In the present study, we investigated the effect
      of CHL on the activation of murine splenocytes stimulated with lipopolysaccharide
      (LPS). RT-PCR analysis showed that LPS-activated IFN-gamma expression gradually
      declined by CHL treatment in a dose dependent manner while mRNA production of TNF
      alpha, IL-2, and FasL was not changed. CHL also suppressed IL-12 production (p70,
      a heterodimer of p40 and p35) and the mRNA expression of IL-12 p40 and IL-12
      receptors (both IL-12Rbeta1 and IL-12Rbeta2), which are involved in the induction
      of IFN-gamma expression. Furthermore, an electrophoretic mobility shift assay
      showed that CHL inhibited DNA binding activity of NF-kappaB, STAT-3, and STAT-4
      to their cognate DNA recognition motifs, all of which contribute to the IL-12
      induced IFN-gamma transcription. Exogenous addition of recombinant IL-12
      abrogated the inhibitory effect of CHL on IFN-gamma and its mRNA expression in
      LPS-activated splenocytes. Collectively, these results show that CHL inhibits IFN
      gamma production by LPS-stimulated splenic mononuclear cells due to down
      regulation of IL-12 production.

PMID- 16275628
TI  - Oral tryptic casein hydrolysate enhances phagocytosis by mouse peritoneal and
      blood phagocytic cells but fails to prevent induced inflammation.
AB  - Mouse experiments were conducted in order to find whether oral application of
      tryptic casein hydrolysate (TCH) results in enhancement of phagocytosing capacity
      of murine phagocytic cells as well as whether such application might be of use
      for prevention of inflammatory processes. Phagocytosing capacity of phagocytic
      cells of mice that received oral TCH once daily in a dose of 1.0 mg/g body weight
      dissolved in 0.5 ml of distilled water for five successive days was significantly
      higher (p < 0.05) than that of mice given equivalent volumes of distilled water,
      with a phagocytosing capacity enhancement index being 1.39 and 1.34 regarding
      peritoneal macrophages and blood phagocytic cells, respectively. Taken on the
      other hand, the immunostimulatory effects of oral TCH were found to be not enough
      to prevent mice from inflammation that was induced experimentally using acute
      (paw edema) and contact hypersensitivity models. A possibility for development of
      food protein enzymatic hydrolysates as antimicrobial immunostimulants acting
      through improvement of phagocytic cell functioning is discussed.

PMID- 16275629
TI  - Effect of glutathione depletion on apoptosis induced by thiram in Chinese hamster
      fibroblasts.
AB  - Fungicide thiram, which is also known as an inducer of allergic contact
      dermatitis (ACD), was used as a model compound of thiuram chemicals, and its
      cellular effects were investigated in cultured Chinese hamster V79 cells. The
      level of intracellular reduced glutathione (GSH), protein sulfhydryl (PSH)
      groups, protein carbonyls (PC), membrane lipid peroxidation reflected by enhanced
      thiobarbituric acid reactive substrates (TBARS) production, as well as apoptotic
      effect were determined. The apoptosis induction was determined by assessing DNA
      fragmentation by TUNEL, annexin V binding, and caspases activation assays, using
      fluorescent microscope or flow cytometry, respectively. The concentrations of
      thiram required to induce cellular GSH depletion (by 40-50%), protein, and
      membrane lipid peroxidation (2-fold, and 1.7-fold, respectively), as well as to
      induce apoptosis in V79 Chinese hamster fibroblasts without causing necrosis
      through cytotoxic effects were between 50-100 microM. To investigate the role of
      decreased GSH content in the toxicity of thiram, GSH level was modified prior to
      exposure. Pretreatment of V79 cells with N-acetyl-L-cysteine (NAC), a GSH
      biosynthesis precursor, prevented GSH decrease, PC and TBARS production, as well
      as caspases activation induced by thiram exposure. On the other hand, thiram
      effects were enhanced by the previous depletion of cellular GSH by L-buthionine
      (S,R)-sulfoximine (BSO).

PMID- 16275630
TI  - Distinct immunosuppressive effect by Isodon serra extracts.
AB  - Distinct effect of ent-Kaurene Diterpenoids from Isodon serra on abnormal
      proliferation of murine lymphocytes was examined with MTT assay and Flow
      Cytometry Analyses (FCAS). After choosing the most appropriate monomer from these
      Diterpenoids, we introduced mouse tumescence model to investigate whether it
      could impact cytokine production in vivo with ELISA assay. The result of MTT
      assay showed that four ent-Kaurene Diterpenoids could effectively suppress the
      murine splenic T lymphocytes overproduction stimulated by Concanavalin A, while
      inhibitive effect was softer on normal sleep lymphocytes than the stimulated
      ones. Among four ent-Kaurene Diterpenoids, Enmein was the most sensitive one with
      IC50/EC50 equaling to 1.55. This inhibitive activity was due to interfering DNA
      replication in G1-S stage and to regulating cell cycle according to flow
      cytometry analyses (FCAS) result. Xylene-induced mouse tumescence model result
      further suggested that Enmein depressed the murine ear swelling extent and the
      level of Interleukin-2 in blood serum in a dose-dependent manner. In conclusion,
      it demonstrated that four ent-Kaurene Diterpenoids from I. serra had distinct
      immunosuppressive effect in vitro and in vivo systems, which primarily
      differentiated Enmein from the others. The experimental results provided insight
      into a potential immunosuppressive action of Enmein as a promising drug, though
      profound mechanism remained to be further studied.

PMID- 16275632
TI  - New drugs on the street: an introduction.

PMID- 16275633
TI  - "Rollin' on E": a qualitative analysis of ecstasy use among inner city
      adolescents and young adults.
AB  - Ecstasy use has spread beyond the rave and club scenes into other arenas of party
      culture, and from middle-class America to working-class and low-income
      neighborhoods of large cities. In order to explore ecstasy use among inner city
      adolescents and young adults, we conducted in-depth interviews with 23 poly-drug
      users who had used ecstasy, in Hartford, CT. Most users reported positive
      experiences while on the drug. Negative experiences were most often related to
      poly-drug mixing. However, heavy users (40+ times ever used) experienced negative
      aftereffects, which led them to decide to decrease or halt their use. Some
      participants discussed using ecstasy during sex, and irregular use of condoms.
      These findings point to the need for more in-depth research on MDMA use within
      inner city settings, with a particular focus on ethnic and cultural context, self
      controlled drug use, poly-drug mixing, and sex risk behaviors.

PMID- 16275631
TI  - Anti-allergic properties of the bromeliaceae Nidularium procerum: inhibition of
      eosinophil activation and influx.
AB  - New therapeutic approaches for the treatment of allergic diseases can be aided by
      the development of agents capable of regulating eosinophilic leukocytes. Here, we
      evaluated the anti-allergic properties of a crude extract of the Brazilian
      bromeliaceae Nidularium procerum, focusing on its effects on allergic
      eosinophilia. By studying allergic pleurisy in actively sensitized C57Bl/6 mice,
      we observed that pretreatment with N. procerum (2 mg/kg; i.p.) reduced pleural
      eosinophil influx triggered by allergen challenge. N. procerum was also able to
      reduce lipid body numbers found within infiltrating eosinophils, indicating that
      N. procerum in vivo is able to affect both migration and activation of
      eosinophils. Consistently, pretreatment with N. procerum blocked pleural
      eosinophil influx triggered by PAF or eotaxin, key mediators of the development
      of allergic pleural eosinophilia. The effect of N. procerum was not restricted to
      eosinophils, since N. procerum also inhibited pleural neutrophil and mononuclear
      cell influx. Of note, N. procerum failed to alter the acute allergic reaction,
      characterized by mast cell degranulation, oedema, and cysteinyl leukotriene
      release. N. procerum also had direct effects on murine eosinophils, since it
      inhibited both PAF- and eotaxin-induced eosinophil chemotaxis on an in vitro
      chemotactic assay. Therefore, N. procerum may be a promising anti-allergic
      therapy, inasmuch as it presents potent anti-eosinophil activity.

PMID- 16275634
TI  - The diffusion of ecstasy through urban youth networks.
AB  - Ecstasy is a drug commonly associated with all-night, or all-weekend electronic
      dance events known as raves. Upper- and middle-class clubs, gay bars and clubs,
      and party venues are other common public settings where ecstasy use occurs.
      During the mid to late 1990s its use was reported in locations as distant as
      Australia and New Zealand, England and Scotland, and North America. In the United
      States, use increased dramatically at the end of the millennium, and drug
      monitoring systems began to report its presence among urban youth. Using social
      influence, social marketing and diffusion theory, this paper outlines the micro
      level processes through which ecstasy traveled from downtown clubs catering to
      suburban young adults through urban youth networks through distributors and
      users. The paper is based on participant observation, and in-depth interviews
      with dealers and users collected during the period of peak diffusion 1999-2001,
      and survey data collected from 401 poly-drug users between the ages of 16 and 24
      and collected at two time points from 1999-2002.

PMID- 16275636
TI  - Under the counter: the diffusion of narcotic analgesics to the inner city street.
AB  - During the past decade, there has been a well-documented rise in the non-medical
      use of prescription painkillers, often referred to as narcotics analgesics (NA).
      Relatively little is known, however, about who these users are, the range of
      health and social consequences associated with their use and the presence of
      illicit NA use on the inner city street. Results of a survey conducted with a
      sample of 242 street drug users indicated that NA use is now widespread in the
      inner city, and that it is associated with a number of serious health and
      psychiatric conditions. Other characteristics of this emerging drug user group
      are explored and the need for future research is highlighted.

PMID- 16275635
TI  - When the drug of choice is a drug of confusion: embalming fluid use in inner city
      Hartford, CT.
AB  - This paper examines the use of a new illicit drug--embalming fluid mixtures--in
      Hartford, CT based on a recent assessment of drug consumption in an outreach
      recruited sample of 242 not-in-treatment active drug users. Sociodemographic,
      drug use, and health and social problems of drug users who do and do not use
      embalming fluid mixture are presented, revealing some notable differences between
      these two groups of street drug users. Despite regular consumption, we report
      that embalming fluid mixture users are often uncertain about what is in this new
      drug, despite experiencing often powerful effects. Urine toxicology findings from
      a subsample of individuals who used embalming fluid mixtures in the last 48
      hours, reveal the frequent presence of phencyclidine (PCP) as well as other
      drugs. The public health implications of this new wave of PCP use are assessed.

PMID- 16275637
TI  - Response to trauma in Haitian youth at risk.
AB  - In order to characterize undesirable behavior (drug use, fighting, criminal
      activity) among Haitian youth at risk and determine the relationship between
      traumatic experience and that kind of behavior, investigators recruited 292
      Haitian youths via networks of informal social relations in two zones of
      Miami/Dade County strongly identified with Haitian ethnicity. Each recruit
      responded to an interview schedule eliciting sociodemographic information and
      self-reported activities, including involvement in youth-dominated groups. They
      also reported traumatic experience. Clinicians administered CAPS to a subset of
      those respondents who self reported traumatic experience. Staff ethnographers
      selected respondents for in-depth interviews and family studies to provide
      contextual depth for findings of the interview schedule and the CAPS assessments.
      Although traumatic experience may still play a role in mental health outcomes
      among children, childhood victimization among Haitian children does not appear to
      be related to the drug use and undesirable behaviors associated with unsupervised
      youth, including formation of gangs.

PMID- 16275638
TI  - "De novo" design of peptides with specific lipid-binding properties.
AB  - In this study, we describe an in silico method to design peptides that can be
      made of non-natural amino acids and elicit specific membrane-interacting
      properties. The originality of the method holds in the capacities developed to
      design peptides from any non-natural amino acids as easily as from natural ones,
      and to test the structure stability by an angular dynamics rather than the
      currently-used molecular dynamics. The goal of this study was to design a non
      natural tilted peptide. Tilted peptides are short protein fragments able to
      destabilize lipid membranes and characterized by an asymmetric distribution of
      hydrophobic residues along their helix structure axis. The method is based on the
      random generation of peptides and their selection on three main criteria: mean
      hydrophobicity and the presence of at least one polar residue; tilted insertion
      at the level of the acyl chains of lipids of a membrane; and conformational
      stability in that hydrophobic phase. From 10,000,000 randomly-generated peptides,
      four met all the criteria. One was synthesized and tested for its lipid
      destabilizing properties. Biophysical assays showed that the "de novo" peptide
      made of non-natural amino acids is helical either in solution or into lipids as
      tested by Fourier transform infrared spectroscopy and is able to induce liposome
      fusion. These results are in agreement with the calculations and validate the
      theoretical approach.

PMID- 16275639
TI  - Membrane topology of mouse stearoyl-CoA desaturase 1.
AB  - Stearoyl-CoA desaturase (SCD) is an integral membrane protein anchored in the
      endoplasmic reticulum. It catalyzes the biosynthesis of monounsaturated fatty
      acids that are required for the synthesis of triglycerides, cholesteryl esters,
      and phospholipids. Four mouse isoforms of SCD (SCD1-4) and two human isoforms
      have been characterized. In the current study, we characterize the topology of
      the mouse SCD1 isoform. Hydropathy analysis of the 355-amino acid mouse SCD1
      protein predicts that the protein contains four transmembrane domains (TMDs) and
      three loops connecting the membrane-spanning domains. To define the topology of
      the protein, recombinant SCD1 constructs containing epitope tags were transiently
      expressed in HeLa cells and analyzed by indirect immunofluorescence and cysteine
      derivatization. Our data provide evidence that the N and C termini of SCD1 are
      oriented toward the cytosol with four transmembrane domains separated by two very
      short hydrophilic loops in the ER lumen and one large hydrophilic loop in the
      cytosol. In addition, based on the previous observation that SCD is a thiol
      enzyme, we sought to investigate whether the cysteine residues were essential for
      enzyme activity through mutagenesis studies, and our data suggest that the
      cysteines in SCD are not catalytically essential.

PMID- 16275640
TI  - Arachidonic acid regulates the translocation of 5-lipoxygenase to the nuclear
      membranes in human neutrophils.
AB  - Elevation of the intracellular cAMP concentration in agonist-activated human
      neutrophils (PMN) leads to the concomitant inhibitions of arachidonic acid (AA)
      release, 5-lipoxygenase (5-LO) translocation, and leukotriene (LT) biosynthesis.
      We report herein that exogenous AA completely prevents cAMP-dependent inhibition
      of 5-LO translocation and LT biosynthesis in agonist-activated PMN. Moreover, the
      group IVA phospholipase A2 inhibitor pyrrophenone and the MEK inhibitor U-0126
      inhibited AA release and 5-LO translocation in activated PMN, and these effects
      were also prevented by exogenous AA, demonstrating a functional link between AA
      release and 5-LO translocation. Polyunsaturated fatty acids of the C18 and C20
      series containing at least three double bonds located from carbon 9 (or closer to
      the carboxyl group) were equally effective as AA in restoring 5-LO translocation
      in pyrrophenone-treated agonist-activated PMN. Importantly, experiments with the
      5-LO-activating protein inhibitor MK-0591 and the intracellular Ca2+ chelator
      BAPTA-AM demonstrated that the AA-regulated 5-LO translocation is FLAP- and Ca2+
      dependent. Finally, the redox and competitive 5-LO inhibitors L-685,015, L
      739,010, and L-702,539 (but not cyclooxygenase inhibitors) efficiently
      substituted for AA to reverse the pyrrophenone inhibition of 5-LO translocation,
      indicating that the site of regulation of 5-LO translocation by AA is at or in
      the vicinity of the catalytic site. This report demonstrates that AA regulates
      the translocation of 5-LO in human PMN and unravels a novel mechanism of the cAMP
      mediated inhibition of LT biosynthesis.

PMID- 16275641
TI  - Direct comparison of a stable isolated Hsp70 substrate-binding domain in the
      empty and substrate-bound states.
AB  - The Hsp70 family of molecular chaperones acts to prevent protein misfolding,
      import proteins into organelles, unravel protein aggregates, and enhance cell
      survival under stress conditions. These activities are all mediated by
      recognition of diverse hydrophobic sequences via a C-terminal substrate-binding
      domain. ATP-binding/hydrolysis by the N-terminal ATPase domain regulates the
      interconversion of the substrate-binding domain between low and high affinity
      conformations. The empty state of the substrate-binding domain has been difficult
      to study because of its propensity to bind nearly any available protein chain,
      even if only modestly hydrophobic. We have generated a new stable construct of
      the substrate-binding domain from the Escherichia coli Hsp70, DnaK, which has
      enabled us to compare the empty and peptide-bound conformations using NMR
      chemical shift analysis and hydrogen-deuterium exchange. We have determined that
      the empty state is, overall, quite similar to the peptide-bound state, contrary
      to a previous report. Peptide binding leads to a subtle alteration in the packing
      of the alpha-helical lid relative to the beta-subdomain. Significantly, we have
      shown that the chemical shifts of the substrate-binding domain and the ATPase
      domain do not change when they are placed together in a two-domain construct,
      whether or not peptide is bound, suggesting that, in the absence of nucleotide,
      the two domains of E. coli DnaK do not interact. We conclude that the isolated
      substrate-binding domain exists in a stable high affinity state in the absence of
      influence from a nucleotide-bound ATPase domain.

PMID- 16275642
TI  - Raf60, a novel component of the Rpd3 histone deacetylase complex required for
      Rpd3 activity in Saccharomyces cerevisiae.
AB  - The Rpd3 histone deacetylase complex contains several previously characterized
      proteins, including Rpd3, Sin3, Sds3, Sap30, and Pho23. We purified the Rdp3
      complex to near homogeneity using the tandem affinity purification method. Mass
      spectrometric analysis revealed the presence of a novel component, which we named
      Raf60. We showed that Myc-Raf60 co-fractionated with Rpd3-TAP by gel filtration
      chromatography, and both Myc-Rpd3 and Sin3 co-immunoprecipitated with HA-Raf60.
      In addition, HA-Raf60 immunoprecipitates displayed Rpd3-dependent histone
      deacetylase activity, and raf60 deletion resulted in loss of Rpd3 complex
      activity, as measured by in vitro assays. Furthermore, we found that raf60Delta
      cells exhibited phenotypes similar to those of rpd3Delta cells, including
      derepression of secreted acid phosphatase (Pho5), hypersensitivity to
      cycloheximide, and hypersensitivity to heat shock. Also, we found by reverse
      transcription-PCR that raf60Delta cells, similar to rpd3Delta cells, displayed
      elevated levels of PHO5 and INO1 mRNA. Our results demonstrate that Raf60 is a
      component of the Rpd3 histone deacetylase complex and that it is required for
      normal Rpd3 complex activity and repression of gene expression.

PMID- 16275643
TI  - Control of MYEOV protein synthesis by upstream open reading frames.
AB  - The myeov gene has been isolated by the tumorigenicity assay and is localized at
      chromosome 11q13, a frequent site for chromosomal rearrangements in various
      carcinomas and B-cell neoplasms. In addition, myeov is coamplified with cyclin D1
      and overexpressed in carcinomas of various organs. The mechanisms of myeov
      regulation remain enigmatic. The 5'-untranslated region (5'-UTR) of the myeov
      gene is long, encompasses several upstream AUGs, and is predicted to fold in a
      strong secondary structure, suggesting that its translation might be regulated by
      an internal ribosomal entry site. Here we show that initial experiments using
      monocistronic and dicistronic reporter constructs supported this assumption.
      However, the application of in vitro transcription/translation assays, Northern
      blot analysis, and promoterless dicistronic constructs revealed promoter activity
      of the myeov 5'-UTR. DNA transfection of dicistronic DNA constructs, normal and
      mutated forms of myeov cDNA fragments cloned in a eukaryotic expression vector,
      and direct RNA transfection analysis revealed that upstream AUG triplets in the
      5'-UTR of the myeov transcript abrogate translation. Alternative splicing
      mechanisms in specific cell types and/or developmental stage may evade this
      translation control. Control experiments suggest that the 5'-UTR from
      encephalomyocarditis virus, when inserted at the midpoint of a dicistronic
      vector, is also able to function as a cryptic promoter.

PMID- 16275644
TI  - Gbetagamma activation site in adenylyl cyclase type II. Adenylyl cyclase type III
      is inhibited by Gbetagamma.
AB  - The Gbetagamma complex of heterotrimeric G proteins is the most outstanding
      example for the divergent regulation of mammalian adenylyl cyclases. The
      heterodimeric Gbetagamma complex inhibits some isoforms, e.g. ACI, and stimulates
      the isoforms ACII, -IV, and -VII. Although former studies identified the QEHA
      region located in the C2 domain of ACII as an important interaction site for
      Gbetagamma, the determinant of the stimulatory effect of Gbetagamma has not been
      detected. Here, we identified the C1b domain as the stimulatory region using full
      length adenylyl cyclase. The relevant Gbetagamma signal transfer motif in IIC1b
      was determined as MTRYLESWGAAKPFAHL (amino acids 493-509). Amino acids of this
      PFAHL motif were absolutely necessary for ACII to be stimulated by Gbetagamma,
      whereas they were dispensable for Galpha(s) or forskolin stimulation. The PFAHL
      motif is present in all three adenylyl cyclase isoforms that are activated by
      Gbetagamma but is absent in other adenylyl cyclase isoforms as well as other
      known effectors of Gbetagamma. The emerging concept of two contact sites on
      different molecule halves for effective regulation of adenylyl cyclase is
      discussed.

PMID- 16275645
TI  - The F-box protein FBX4 targets PIN2/TRF1 for ubiquitin-mediated degradation and
      regulates telomere maintenance.
AB  - Pin2/TRF1 was identified previously as both a protein (TRF1) that binds to
      telomeric DNA repeats and as a protein (Pin2) that associates with the kinase
      NIMA and suppresses its mitosis inducing activity. Pin2/TRF1 negatively regulates
      telomere length and also plays a critical role in cell cycle checkpoint control.
      Pin2/TRF1 is down-regulated in many human cancers and may be degraded by the
      ubiquitin-proteasome pathway, but components of the pathway involved in Pin2/TRF1
      turnover have not been elucidated. By using the two-hybrid system, we recently
      identified Pin2/TRF1-interacting proteins, PinX1-4, and we demonstrated that
      PinX1 is a conserved telomerase inhibitor and a putative tumor suppressor. Here
      we report the characterization of PinX3. PinX3 was later found to be identical to
      Fbx4, a member of the F-box family of proteins, which function as substrate
      specific adaptors of Cul1-based ubiquitin ligases. Fbx4 interacts with both Pin2
      and TRF1 isoforms and promotes their ubiquitination in vitro and in vivo.
      Moreover, overexpression of Fbx4 reduces endogenous Pin2/TRF1 protein levels and
      causes progressive telomere elongation in human cells. In contrast, inhibition of
      Fbx4 by RNA interference stabilizes Pin2/TRF1 and promotes telomere shortening,
      thereby impairing cell growth. These results demonstrate that Fbx4 is a central
      regulator of Pin2/TRF1 protein abundance and that alterations in the stability of
      Pin2/TRF1 can have a dramatic impact on telomere length. Thus, Fbx4 may play a
      critical role in telomere maintenance.

PMID- 16275646
TI  - RNA polymerase II blockage by cisplatin-damaged DNA. Stability and
      polyubiquitylation of stalled polymerase.
AB  - The consequences of human RNA polymerase II (pol II) arrest at the site of DNA
      damaged by cisplatin were studied in whole cells and cell extracts, with a
      particular focus on the stability of stalled pol II and its subsequent
      ubiquitylation. Site-specifically platinated DNA templates immobilized on a solid
      support were used to perform in vitro transcription in HeLa nuclear extracts. RNA
      elongation was completely blocked by a cisplatin intrastrand cross-link. The
      stalled polymerase was quite stable, remaining on the DNA template in nuclear
      extracts. The stability of pol II stalled at the site of cisplatin damage was
      also observed in live cells. A cell fractionation experiment using cisplatin
      treated HeLa cells revealed an increased level of chromatin-associated pol II
      proteins following DNA damage. The stalled polymerase was transcriptionally
      active and capable of elongating the transcript following chemical removal of
      platinum from the template. Transcription inhibition by alpha-amanitin in vitro
      enhanced pol II ubiquitylation at ubiquitin residues Lys-6, Lys-48, and Lys-63.
      In live cells expressing epitope-tagged ubiquitin mutants, several ubiquitin
      lysines also participated in pol II ubiquitylation following DNA damage.
      Cisplatin treatment triggered ubiquitylation-mediated pol II degradation in HeLa
      cells, which could be prevented by the proteasomal inhibitor MG132. Fractionation
      of pol II from cells co-treated with MG132 and cisplatin indicated that the
      undegraded ubiquitylated polymerase was mostly unbound or only loosely associated
      with chromatin. These data are consistent with a model in which only a fraction
      of pol II, ubiquitylated in response to cisplatin damage of DNA, dissociates from
      the sites of platination. This altered polymerase is rapidly destroyed by
      proteasomes.

PMID- 16275647
TI  - Rational development of beta-peptide inhibitors of human cytomegalovirus entry.
AB  - Human cytomegalovirus (HCMV) is a pervasive and significant pathogen. At present,
      there is no HCMV vaccine, and the available drugs target only replication events.
      Thus, new therapeutic strategies are needed. HCMV fusion appears to require
      interactions of alpha-helical regions in viral surface glycoproteins gB and gH.
      Oligomers of beta-amino acids ("beta-peptides") are attractive unnatural
      scaffolds for mimicry of specific protein surfaces, because beta-peptides adopt
      predictable helical conformations and resist proteolysis. Here, we report the
      development of beta-peptides designed to mimic the gB heptad repeat and block
      HCMV entry. The most potent beta-peptide inhibits HCMV infection in a cell based
      assay with an IC50 of approximately 30 microm. Consistent with our structure
      based design strategy, inhibition is highly specific for HCMV relative to other
      related viruses. Mechanistic studies indicate that inhibitory beta-peptides act
      by disrupting membrane fusion. Our findings raise the possibility that beta
      peptides may provide a general platform for development of a new class of
      antiviral agents and that inhibitory beta-peptides will constitute new tools for
      elucidating viral entry mechanisms.

PMID- 16275648
TI  - Basic residues in the nucleocapsid domain of Gag are required for interaction of
      HIV-1 gag with ABCE1 (HP68), a cellular protein important for HIV-1 capsid
      assembly.
AB  - During human immunodeficiency virus, type 1 (HIV-1) assembly, Gag polypeptides
      multimerize into immature HIV-1 capsids. The cellular ATP-binding protein ABCE1
      (also called HP68 or RNase L inhibitor) appears to be critical for proper
      assembly of the HIV-1 capsid. In primate cells, ABCE1 associates with Gag
      polypeptides present in immature capsid assembly intermediates. Here we
      demonstrate that the NC domain of Gag is critical for interaction with endogenous
      primate ABCE1, whereas other domains in Gag can be deleted without eliminating
      the association of Gag with ABCE1. NC contains two Cys-His boxes that form zinc
      finger motifs and are responsible for encapsidation of HIV-1 genomic RNA. In
      addition, NC contains basic residues known to play a critical role in nonspecific
      RNA binding, Gag-Gag interactions, and particle formation. We demonstrate that
      basic residues in NC are needed for the Gag-ABCE1 interaction, whereas the
      cysteine and histidine residues in the zinc fingers are dispensable. Constructs
      that fail to interact with primate ABCE1 or interact poorly also fail to form
      capsids and are arrested at an early point in the immature capsid assembly
      pathway. Whereas others have shown that basic residues in NC bind nonspecifically
      to RNA, which in turn scaffolds or nucleates assembly, our data demonstrate that
      the same basic residues in NC act either directly or indirectly to recruit a
      cellular protein that also promotes capsid formation. Thus, in cells, basic
      residues in NC appear to act by two mechanisms, recruiting both RNA and a
      cellular ATPase in order to facilitate efficient assembly of HIV-1 capsids.

PMID- 16275649
TI  - Quantifying the specific binding between West Nile virus envelope domain III
      protein and the cellular receptor alphaVbeta3 integrin.
AB  - A previous study has illustrated that the alphaVbeta3 integrin served as the
      functional receptor for West Nile virus (WNV) entry into cells. Domain III (DIII)
      of WNV envelope protein (E) was postulated to mediate virus binding to the
      cellular receptor. In this study, the specificity and affinity binding of WNV E
      DIII protein to alphaVbeta3 integrin was confirmed with co-immunoprecipitation
      and receptor competition assay. Binding of WNV E DIII protein to alphaVbeta3
      integrin induced the phosphorylation of focal adhesion kinase that is required to
      mediate ligand-receptor internalization into cells. A novel platform was then
      developed using the atomic force microscopy to measure this specific binding
      force between WNV E DIII protein and the cellular receptor, alphaVbeta3 integrin.
      The single protein pair-interacting force measured was in the range of 45 +/- 5
      piconewtons. This interacting force was highly specific as minimal force was
      measured in the WNV E DIII protein interaction with alphaVbeta5 integrin
      molecules and heparan sulfate. These experiments provided an insight to
      quantitate virus-receptor interaction. Force measurement using atomic force
      microscopy can serve to quantitatively analyze the effect of candidate drugs that
      modulate virus-host receptor affinity.

PMID- 16275650
TI  - Altered HIV-1 Gag protein interactions with cyclophilin A (CypA) on the
      acquisition of H219Q and H219P substitutions in the CypA binding loop.
AB  - HIV-1 Gag protein interaction with cyclophilin A (CypA) is critical for viral
      fitness. Among the amino acid substitutions identified in Gag noncleavage sites
      in HIV-1 variants resistant to protease inhibitors, H219Q (Gatanaga, H., Suzuki,
      Y., Tsang, H., Yoshimura, K., Kavlick, M. F., Nagashima, K., Gorelick, R. J.,
      Mardy, S., Tang, C., Summers, M. F., and Mitsuya, H. (2002) J. Biol. Chem. 277,
      5952-5961) and H219P substitutions in the viral CypA binding loop confer the
      greatest replication advantage to HIV-1. These substitutions represent
      polymorphic amino acid residues. We found that the replication advantage
      conferred by these substitutions was far greater in CypA-rich MT-2 and H9 cells
      than in Jurkat cells and peripheral blood mononuclear cells (PBM), both of which
      contained less CypA. High intracellular CypA content in H9 and MT-2 cells,
      resulting in excessive CypA levels in virions, limited wild-type HIV-1 (HIV
      1(WT)) replication and H219Q introduction into HIV-1 (HIV-1(H219Q)), reduced CypA
      incorporation of HIV-1, and potentiated viral replication. H219Q introduction
      also restored the otherwise compromised replication of HIV-1(P222A) in PBM,
      although the CypA content in HIV-1(H219Q/P222A) was comparable with that in HIV
      1(P222A), suggesting that H219Q affected the conformation of the CypA-binding
      motif, rendering HIV-1 replicative in a low CypA environment. Structural modeling
      analyses revealed that although hydrogen bonds are lost with H219Q and H219P
      substitutions, no significant distortion of the CypA binding loop of Gag
      occurred. The loop conformation of HIV-1(P222A) was found highly distorted,
      although H219Q introduction to HIV-1 restored the conformation of the loop close
      to that of HIV-1 (P222A). The present data suggested that the effect of CypA on
      HIV-1 replicative (WT) ability is bimodal (both high and low CypA content limits
      HIV-1 replication), that the conformation of the CypA binding region of Gag is
      important for viral fitness, and that the function of CypA is to maintain the
      conformation.

PMID- 16275651
TI  - Structural basis for membrane anchorage of viral phi29 DNA during replication.
AB  - Prokaryotic DNA replication is compartmentalized at the cellular membrane.
      Functional and biochemical studies showed that the Bacillus subtilis phage 29
      encoded membrane protein p16.7 is directly involved in the organization of
      membrane-associated viral DNA replication. The structure of the functional domain
      of p16.7 in complex with DNA, presented here, reveals the multimerization mode of
      the protein and provides insights in the organization of the phage genome at the
      membrane of the infected cell.

PMID- 16275652
TI  - Effects of new smoking regulations in Italy.
AB  - BACKGROUND: From 10 January 2005 the Italian government banned smoking in all
      indoor public places. We conducted a population-based survey to provide
      information on attitudes towards smoking regulation and to disentangle the impact
      of the smoking ban on tobacco consumption. PATIENTS AND METHODS: We considered
      data from a survey on smoking, based on 3114 subjects aged 15 or over,
      representative of the general adult Italian population in terms of age, sex,
      geographic area and socioeconomic status. RESULTS: Once smoke-free policies were
      introduced, support for them in the public opinion tended to increase. In Italy,
      smoke-free policies accounted for around 8% decrease in cigarette consumption in
      the short run. Moreover, tobacco bans were almost universally accepted, and the
      smoke-free legislation did not seem to unfavourably affect the business of
      restaurants or cafes. CONCLUSIONS: The results of our study on the first
      extensive smoking ban in a large country show the advantages of smoke-free
      legislations, which may have major public health implications.

PMID- 16275653
TI  - Phase I and pharmacokinetic study of oral fludarabine phosphate in relapsed
      indolent B-cell non-Hodgkin's lymphoma.
AB  - BACKGROUND: The primary objective of this study was to investigate the
      tolerability, efficacy and pharmacokinetic profile of oral fludarabine phosphate
      in relapsed patients with indolent B-cell non-Hodgkin's lymphoma (B-NHL).
      PATIENTS AND METHODS: Patients received fludarabine phosphate orally for 5 days,
      for a total of one to three cycles. Tolerability was assessed using the National
      Cancer Institute Common Toxicity Criteria. Efficacy was assessed using the
      International Workshop Criteria for NHL. Pharmacokinetic samples were taken on
      day 1 and day 5 of the first treatment cycle. RESULTS: Twelve patients were
      enrolled. One patient at 40 mg/m2/day developed grade 4 hyperuricemia. At 50
      mg/m2/day, one patient developed grade 3 febrile neutropenia and grade 4
      leukopenia, and another patient showed lasting grade 4 neutropenia. Most common
      toxicities included grade 3 or 4 lymphopenia (83%), leukopenia (50%) and
      neutropenia (50%). All the toxicities were reversible. The overall response rate
      was 67%. The AUC0-24h values on day 5 indicated a dose-dependent increase in
      systemically available 2-fluoro-arabinofuranosyl-adenine (2F-ara-A). CONCLUSIONS:
      Oral fludarabine phosphate is safe and effective for relapsed patients with
      indolent B-NHL. The dose of 40 mg/m2/day is recommended for a following pivotal
      phase II study.

PMID- 16275655
TI  - A systematic review of prevalence and risk factors associated with playing
      related musculoskeletal disorders in pianists.
AB  - BACKGROUND: Playing-related musculoskeletal disorders (PRMDs) are a recognized
      problem amongst instrumental musicians. Although pianists are prominent in data
      regarding prevalence of PRMDs, there is poor understanding of piano-specific risk
      factors associated with PRMDs. AIM: To synthesize published literature on the
      prevalence of and risk factors associated with PRMDs in pianists. METHODS: Thirty
      eight databases were searched. Eligible studies were those investigating
      prevalence of or risk factors associated with PRMDs in pianists, using an
      appropriate methodology according to a hierarchy of evidence. Information
      regarding study population, operational definition of PRMD, risk factors
      investigated, statistical tests used and outcomes was extracted and narratively
      synthesized for all eligible papers above an arbitrarily chosen quality score.
      RESULTS: The literature search identified 482 citations. Fifty-two papers were
      ranked in a hierarchy of evidence; 12 were eligible for evaluation using a
      quality assessment tool. Common methodological limitations included
      sampling/measurement biases, inadequate reporting of reliability/validity of
      outcome measures, lack of operational definition of PRMD and no statistical
      significance testing. Prevalence rates for PRMDs in pianists varied widely (26
      93%). Four authors demonstrated statistically significant risk factors; however,
      no authors combined a clear operational definition of PRMD with statistically
      established risk factors. There was no consensus between authors regarding risk
      factors. CONCLUSIONS: Current evidence does not provide sufficient information
      regarding prevalence of and risk factors associated with PRMDs in pianists.
      Future studies should provide an operational definition of PRMD, use valid,
      reliable measurement tools, utilize a prospective cohort study design and perform
      appropriate statistical tests.

PMID- 16275656
TI  - Occupational fitness standards for beach lifeguards. Phase 1: the physiological
      demands of beach lifeguarding.
AB  - BACKGROUND: Although similar standards exist internationally to select beach
      lifeguards (BLGs), these are generally not based on a task analysis. To reduce
      the likelihood of drowning, a BLG should reach a casualty within 3.5 min (210 s).
      AIM: To quantify the physical demands of the most critical generic tasks
      undertaken by BLGs. METHODS: A survey of 91 BLGs identified sea swimming while
      towing a casualty, board paddling with a casualty, and casualty handling as the
      most demanding activities. Performance during beach running (200 m), swimming in
      the sea (200 m), board paddling in the sea (400 m), swimming in a pool (200 m
      freestyle and 25 m underwater with 25 m return) and simulated casualty handling
      were measured. RESULTS: The median area at sea patrolled by paddling and swimming
      was 400 m. The mean 200-m sea swim time was 3.1 min or 188 s (SD = 46 s) and 95%
      of the BLGs were able to swim 200 m in 3.5 min (n = 22). The mean time to paddle
      400 m was 3.8 min or 226 s (SD = 35 s) and 30% of the BLGs were able to paddle
      400 m in 3.5 min (n = 23). The 5th percentile paddling speed was 1.38 m/s,
      therefore, 95% of the BLGs tested should be able to paddle 289 m in 3.5 min.
      CONCLUSIONS: If only a rescue board is available, the area out to sea patrolled
      by a lifeguard should be reduced from 400 m to 300 m.

PMID- 16275657
TI  - Expression of the vacuolar Ca2+/H+ exchanger, OsCAX1a, in rice: cell and age
      specificity of expression, and enhancement by Ca2+.
AB  - Calcium is an essential macronutrient for plants and functions in signal
      transduction. Regulation of the cytosolic calcium concentration is required for
      normal cell growth. In calcium homeostasis in plant cells, Ca(2+)/H(+) exchangers
      are involved in Ca(2+) compartmentalization into intracellular compartments.
      Here, we examine the intracellular localization of a rice Ca(2+)/H(+) exchanger,
      OsCAX1a, fused to a green fluorescent protein and transiently expressed in onion
      epidermis and rice protoplasts. Green fluorescence was observed in the vacuolar
      membrane. After sucrose gradient centrifugation of the homogenate of rice plants,
      OsCAX1a was detected in the same fraction as the vacuolar membrane aquaporin
      gamma-TIP. We then quantified the mRNA and protein of OsCAX1a in plants grown
      with metal ions. OsCAX1a mRNA was induced in roots by high concentrations of
      Ca(2+). The protein level in shoots was also increased in the presence of high
      concentrations of Ca(2+). Furthermore, transgenic rice plants transformed with
      the OsCAX1a promoter fused to beta-glucuronidase showed reporter expression in
      vascular bundles, stomata, trichomes, steles, flowers, embryos and aleurone
      layers. In the case of stomata and trichomes, transcription of OsCAX1a was
      particularly high in aged organs. These results suggest that OsCAX1a transports
      Ca(2+) into vacuoles and is involved in Ca(2+) homeostasis in cells that suffer
      from high concentrations of Ca(2+).

PMID- 16275658
TI  - Large-scale systematic study on stability of the Ds element and timing of
      transposition in rice.
AB  - Activator/Dissociation (Ac/Ds) transposon mutagenesis is a widely used tool for
      gene identification; however, several reports on silencing of the Ac/Ds element
      in starter lines and in stable transposants question the applicability of such an
      approach in later generations. We have performed a systematic analysis on various
      aspects of the silencing phenomenon in rice (Oryza sativa ssp. japonica cv.
      Nipponbare). High somatic and germinal transposition frequencies observed in
      earlier generations were maintained as late as T4 and T5 generations; thus the
      propagation of parental lines did not induce transposon silencing. Moreover, the
      stably transposed Ds element was active even at the F5 generation, since Ac could
      remobilize the Ds element as indicated by the footprint analysis of several
      revertants. Expression of the bar gene was monitored from F3 to F6 generations in
      >1,000 lines. Strikingly, substantial transgene silencing was not observed in any
      of the generations tested. We analyzed the timing of transposition during rice
      development and provide evidence that Ds is transposed late after tiller
      formation. The possibility, that the independent events could be the result of
      secondary transposition, was ruled out by analyzing potential footprints by
      reciprocal PCR. Our study validates the Ac/Ds system as a tool for large-scale
      mutagenesis in rice, since the Ds elements were active in the starter and
      insertion lines even in the later generations. We propose that harvesting rice
      seeds using their panicles is an alternative way to increase the number of
      independent transposants due to post-tillering transposition.

PMID- 16275659
TI  - Use of a prospective risk analysis method to improve the safety of the cancer
      chemotherapy process.
AB  - OBJECTIVE: To perform a risk analysis of the cancer chemotherapy process, by
      comparing five different organizations. To quantitatively demonstrate the
      usefulness of centralization and information technologies, to identify residual
      risks that may be the target of additional actions. STUDY DESIGN: A reengineering
      of the process started in 1999 and was planned to be finished in 2006. The
      analysis was performed after the centralization and at the beginning of
      information technologies integration. SETTING: Two thousand two hundred beds
      university hospital, with medical, surgical, haematological, gynaecological,
      geriatric, paediatric oncological departments. Twelve thousand cancer
      chemotherapies each year. METHODS: According to the failure modes, effects and
      criticality analysis (FMECA) method, the failure modes were defined and their
      criticality indexes were calculated on the basis of the likelihood of occurrence,
      the potential severity for the patients, and the detection probability.
      Criticality indexes were compared and the acceptability of residual risks was
      evaluated. RESULTS: The sum of criticality indexes of 27 identified failure modes
      was 3596 for the decentralized phase, 2682 for centralization, 2385 for
      electronic prescription, 2081 for electronic production control, and 1824 for
      bedside scanning (49% global reduction). The greatest improvements concerned the
      risk of errors in the production protocols (by a factor of 48), followed by
      readability problems during transmission (14) and product/dose errors during the
      production (8). Among the six criticality indexes remaining superior to 100 in
      the final process, two were judged to be acceptable, whereas further improvements
      were planned for the four others. CONCLUSIONS: Centralization to the pharmacy was
      associated with a strong improvement but additional developments involving
      information technologies also contributed to a major risk reduction. A cost
      effect analysis confirmed the pertinence of all developments, as the cost per
      gained criticality point remained stable all over the different phases.

PMID- 16275660
TI  - Identification of VCP/p97, carboxyl terminus of Hsp70-interacting protein (CHIP),
      and amphiphysin II interaction partners using membrane-based human proteome
      arrays.
AB  - Proteins mediate their biological function through interactions with other
      proteins. Therefore, the systematic identification and characterization of
      protein-protein interactions have become a powerful proteomic strategy to
      understand protein function and comprehensive cellular regulatory networks. For
      the screening of valosin-containing protein, carboxyl terminus of Hsp70
      interacting protein (CHIP), and amphiphysin II interaction partners, we utilized
      a membrane-based array technology that allows the identification of human protein
      protein interactions with crude bacterial cell extracts. Many novel interaction
      pairs such as valosin-containing protein/autocrine motility factor receptor,
      CHIP/caytaxin, or amphiphysin II/DLP4 were identified and subsequently confirmed
      by pull-down, two-hybrid and co-immunoprecipitation experiments. In addition,
      assays were performed to validate the interactions functionally. CHIP e.g. was
      found to efficiently polyubiquitinate caytaxin in vitro, suggesting that it might
      influence caytaxin degradation in vivo. Using peptide arrays, we also identified
      the binding motifs in the proteins DLP4, XRCC4, and fructose-1,6-bisphosphatase,
      which are crucial for the association with the Src homology 3 domain of
      amphiphysin II. Together these studies indicate that our human proteome array
      technology permits the identification of protein-protein interactions that are
      functionally involved in neurodegenerative disease processes, the degradation of
      protein substrates, and the transport of membrane vesicles.

PMID- 16275661
TI  - Mending the rhythm does not improve prognosis in patients with persistent atrial
      fibrillation: a subanalysis of the RACE study.
AB  - AIMS: To compare outcome of AF patients with effective rhythm control with
      patients treated with rate control. METHODS AND RESULTS: Out of the 266 AF
      patients randomized to rhythm control in the RACE study, 49 patients turned to
      long-term sinus rhythm and were continuously treated with oral anticoagulation.
      The incidence of the primary endpoint in these patients was compared to that in
      178 patients out of the initial 256 rate-control patients of RACE who were in AF
      and using oral anticoagulation continuously. Baseline characteristics of both
      groups were not different. After a mean follow-up of 2.3+/-0.6 years, the primary
      endpoint (a composite of cardiovascular mortality, heart failure, thrombo-embolic
      complications (TECs), bleeding, serious adverse effects of antiarrhythmic drugs
      and pacemaker implants) was 22.4% in the rhythm-control group vs. 15.2% in the
      rate-control group. Multivariable regression analysis indicated coronary artery
      disease, heart failure, and digitalis as independent risk indicators of
      cardiovascular morbidity and mortality. Chronic sinus rhythm did not matter.
      CONCLUSION: Among patients who remained on warfarin, those who mostly were
      maintained in sinus rhythm under a rhythm-control strategy did not have a
      superior prognosis compared to those who remained in AF under a rate-control
      strategy.

PMID- 16275662
TI  - Thingamijigs, wotsits and the naming of things.

PMID- 16275663
TI  - Exploring a massage intervention for parents and their children with autism: the
      implications for bonding and attachment.
AB  - This exploratory study aimed to address two questions: (1) What does touch mean
      between parents and their children with autism on completion of a massage
      intervention? (2) Do parents feel that their relationship with their children has
      changed on completion of a massage intervention? Fourteen parents agreed to be
      interviewed. Data were collected before the massage intervention (baseline),
      immediately after the massage intervention and 16 weeks from baseline and were
      analysed using interpretative phenomenological analysis. At baseline, parents
      felt distressed that they felt unable to get 'close' to their children. After the
      intervention, parents reported feeling physically and emotionally closer to their
      children. Children expressed a range of cues to initiate massage at home. These
      benefits were maintained at follow-up for parents who continued to use massage at
      home. In conclusion, giving massage to children with autism may help to enhance
      the emotional bond between parent and child.

PMID- 16275664
TI  - Liver transplantation in children: part 1--peri-operative issues.
AB  - This two-part review provides a comprehensive summary of clinical and research
      literature on paediatric liver transplantation. Part 1 outlines the peri
      operative issues of liver transplantation, covers a brief history, discusses the
      indications and methods of transplantation and outlines the physical
      complications which can occur either as a result of the surgery or the subsequent
      immunosuppressive therapy required to maintain graft integrity. Post-liver
      transplantation care may require prolonged admission in hospital due to the
      complications that can occur during surgery and as a result of immunosuppression.
      This can have a further impact on the emotional status of the child and family.
      Health care professionals in all settings require greater knowledge about
      paediatric liver transplantation, its associated complications and long-term
      health implications.

PMID- 16275665
TI  - Liver transplantation in children: part 2--long-term issues.
AB  - This two-part review provides a comprehensive summary of clinical and research
      literature on paediatric liver transplantation. Part 2 focuses on the long-term
      physical consequences and psychological impact of transplantation and critically
      examines neurobehavioural, sexual development, psychosocial function and overall
      impact on children's quality of life. This review highlights the implications for
      clinical practice in specialist and local services and suggests areas where
      research is required to improve the lives of children after liver
      transplantation.

PMID- 16275666
TI  - Mothers' stories of loss: their need to be with their dying child and their
      child's body after death.
AB  - Children die every year in the UK from a range of life-limiting conditions. The
      majority will die in hospital as only a minority die at home or in children's
      hospices. There is a paucity of research exploring the experiences of mothers
      whose children die in these settings. Although the need for them to be in a
      caring and supportive environment seems self-evident, this qualitative study
      finds that not all provide this. Interviews with 10 mothers enabled comparisons
      to be made between care and support received in hospital, at home and in a
      children's hospice. Their stories identified their need for time, space and
      privacy with their dying child and their child's body after death. Also, that
      memories of these events continued to affect them, giving further support to new
      theoretical understandings of parental grief which suggest that parents maintain
      continuing bonds with their dead child by preserving memories and recollections
      of their life and death.

PMID- 16275667
TI  - A pilot study on enhancing positive coping behaviour in early adolescents using a
      school-based project.
AB  - Early adolescence is a period of rapid cognitive, social, emotional and physical
      changes. During this period, early adolescents usually lack the ability to cope
      when they experience stress, which is usually family and school-related. If they
      cannot cope with such stress, they may fail to develop in a healthy manner and
      may develop habits harmful to their health such as substance abuse. To enhance
      positive behaviour in those in early adolescence coping with stress, a school
      based project was implemented using focus group interviews, an open forum and
      follow-up interviews and journals. The objectives were to identify the stressors
      encountered by the students and their ability to cope, to develop and implement
      an educational activity to promote positive coping behaviour and to evaluate the
      effectiveness of the educational activity. The findings of the evaluation support
      the view that an early prevention programme for promoting positive coping
      behaviour to early adolescents is useful.

PMID- 16275668
TI  - Being ill as narrated by children aged 11-18 years.
AB  - Being ill from a child's perspective has not been often investigated. The aim of
      this study was to illuminate the experience of being ill between the ages of 11
      18 years. Four girls and one boy who were suffering short-term illness were
      interviewed and the data obtained subjected to qualitative content analysis.
      Illness disrupted their daily lives and made things unrecognizable. Being ill at
      the age of 11-18 seemed to imply being lost, hurt and in need of comfort from
      themselves and others. These narrations may indicate to health care professionals
      how they can improve their practice. This study suggests what is appreciated by
      children of this age when ill, namely being spoken to and informed about the
      illness and treatment. The children valued peace and quiet and wanted to listen
      to and adjust to their bodies.

PMID- 16275670
TI  - Uptake of sodium in protoplasts of salt-sensitive and salt-tolerant cultivars of
      rice, Oryza sativa L. determined by the fluorescent dye SBFI.
AB  - In this study, the uptake of Na+ into the cytosol of rice (Oryza sativa L. cvs
      Pokkali and BRRI Dhan29) protoplasts was measured using the acetoxy methyl ester
      of the fluorescent sodium-binding benzofuran isopthalate, SBFI-AM, and
      fluorescence microscopy. By means of inhibitor analyses the mechanisms for uptake
      and sequestration of Na+ in the salt-sensitive indica rice cv. BRRI Dhan29 and in
      the salt-tolerant indica rice cv. Pokkali were detected. Less Na+ was taken up
      into the cytosol of Pokkali than into BRRI Dhan29. The results indicate that K+
      selective channels do not contribute to the Na+ uptake in Pokkali, whereas they
      are the major pathways for Na+ uptake in BRRI Dhan29 along with non-selective
      cation channels. However, non-selective cation channels seem to be the main
      pathways for Na+ uptake in Pokkali. Protoplasts from Pokkali leaves took up Na+
      only transiently in the presence of extracellular Na+ at 5-100 mM. Therefore, it
      is likely that the protoplasts have a mechanism for fast extrusion of Na+ out of
      the cytoplasm. Experiments with protoplasts pretreated with NH4NO3 and NH4VO3
      suggest that the salt-tolerant Pokkali extrudes Na+ mainly into the vacuole.
      After cultivation of both cultivars in the presence of 10 or 50 mM NaCl for 72 h,
      the isolated protoplasts from Pokkali took up less Na+ than the control
      protoplasts. The results suggest that the salt-tolerance in Pokkali depends on
      reduced uptake through K+-selective channels and a fast extrusion of Na+ into the
      vacuoles.

PMID- 16275671
TI  - Functional analysis of a putative Ca2+ channel gene TaTPC1 from wheat.
AB  - The cytosolic free-calcium concentration [Ca2+](cyt) transiently increases under
      abiotic stresses and the proteins that control this process are gradually
      disclosed. The Ca2+-permeable channel is one type of these proteins in plants. In
      the present study, a novel Ca2+-permeable channel gene TaTPC1 encoding a putative
      membrane protein was cloned from wheat. It was induced under high salinity,
      polyethylene glycol, low temperature (4 degrees C), and abscisic acid. Expression
      of TaTPC1 in the yeast mutant lacking CCH1 can recover its growth under lithium
      stress through functional complementation. TaTPC1 transgenic plants exhibited
      more stomatal closing in the presence of Ca2+ than the control, supporting a role
      for the calcium channel in regulating plant responses to environmental change.

PMID- 16275673
TI  - Is there any role for sentinel node mapping in colorectal cancer staging?
      Personal experience and review of the literature.
AB  - BACKGROUND: We explored the role of lymphatic mapping and sentinel
      lymphadenectomy (originally described for melanoma and breast cancer) in colon
      cancer. Pathologic techniques can successfully identify micrometastatic disease
      in lymph nodes, but they are not suitable for clinical routine use. We evaluated
      the role of sentinel node (SN) mapping in refining the staging of colorectal
      cancer. METHODS: A total of 56 open colorectal resections were performed, and
      Patent Blue V dye was injected under the serosa surrounding the tumor immediately
      after opening the abdomen. SNs were analysed by immunohistochemistry to find
      micrometastatic disease. A literature search for the role of SNs in colorectal
      cancer was also performed. RESULTS: We identified the SN in 100% of patients,
      with a mean of 2.02 SNs/patient (range 1-5). After immunohistochemical staining,
      we could upstage 21 out of 56 patients (37.5%), and we observed 10.7% false
      negative SNs (6/56 patients). Fewer than half of the articles described false
      negative rates of <15%, and most articles showed an upstaging rate of >5% of
      patients. These differences are probably the result of different sensitivities of
      the methods used in identifying the lymph node micrometastases. CONCLUSIONS: SN
      mapping is an easy and cost-effective technique that holds promise and warrants
      further investigations.

PMID- 16275672
TI  - Expression profiling of genes involved in starch synthesis in sink and source
      organs of rice.
AB  - A comprehensive analysis of the transcript levels of genes which encode starch
      synthesis enzymes is fundamental for the assessment of the function of each
      enzyme and the regulatory mechanism for starch biosynthesis in source and sink
      organs. Using quantitative real-time RT-PCR, an examination was made of the
      expression profiles of 27 rice genes encoding six classes of enzymes, i.e.
      ADPglucose pyrophosphorylase (AGPase), starch synthase, starch branching enzyme,
      starch debranching enzyme, starch phosphorylase, and disproportionating enzyme in
      developing seeds and leaves. The modes of gene expression were tissue- and
      developmental stage-specific. Four patterns of expression in the seed were
      identified: group 1 genes, which are expressed very early in grain formation and
      are presumed to be involved in the construction of fundamental cell machineries,
      de novo synthesis of glucan primers, and initiation of starch granules; group 2
      genes, which are highly expressed throughout endosperm development; group 3
      genes, which have transcripts that are low at the onset but which rise steeply at
      the start of starch synthesis in the endosperm and are thought to play essential
      roles in endosperm starch synthesis; and group 4 genes, which are expressed
      scantly, mainly at the onset of grain development, and might be involved in
      synthesis of starch in the pericarp. The methodology also revealed that the
      defect in the cytosolic AGPase small subunit2b (AGPS2b) transcription from the
      AGPS2 gene in endosperm sharply enhanced the expressions of endosperm and leaf
      plastidial AGPS1, the endosperm cytosolic AGPase large subunit2 (AGPL2), and the
      leaf plastidial AGPL1.

PMID- 16275674
TI  - A case of rectosigmoid cancer metastasizing to a fistula in ano.
AB  - We herein report a case of rectosigmoid cancer metastasizing to a fistula in ano.
      A 53-year-old man complaining of anal bleeding consulted another hospital. He had
      been suffering from an anal fistula since 7 years. On the left upper side of the
      skin surface around the anus a fistula end was seen as a hole that tunneled down
      into the back passage, although no hard tumor was palpable on the hole. Complete
      colonoscopy revealed an ulcerative tumor in the rectosigmoid colon. On 5 February
      2004, anterior resection and lymphadenectomy was performed. The post-operative
      pathological diagnosis was rectosigmoid cancer, Type 2, T2, N0, M0, stage II. The
      anal fistula was a simple type and mucinous discharge was not observed. On 23
      February 2004, coring out the anal fistula was performed by the former hospital.
      Pathological diagnosis of the excised fistula revealed well-differentiated
      adenocarcinoma; identical to the colon tumor. Immunohistochemical staining of
      these two lesions were negative for (CK) 7 but staining with CK20 revealed some
      stained tumor cells in two lesions. We diagnosed this tumor as metastatic
      adenocarcinoma from a rectosigmoid cancer. Recurrent lesions were not seen during
      the first year after the first operation.

PMID- 16275675
TI  - The 18th International Symposium: Controversies in Prostate Cancer Diagnosis and
      Treatment.

PMID- 16275677
TI  - Preoperative chemotherapy and radiation therapy for squamous cell carcinoma of
      the maxillary sinus.
AB  - OBJECTIVE: This study was undertaken to assess the prognostic factors for the
      management of squamous cell carcinoma (SCC) of the maxillary sinus, who received
      preoperative chemotherapy and radiation therapy (RT). We also elucidated the
      appropriate sequence of chemotherapy. METHODS: A total of 124 patients (median
      age 62 years) with SCC of the maxillary sinus were analysed retrospectively. T3
      or T4 disease was found in 93% of the patients. Thirty-nine patients received
      neoadjuvant chemotherapy (NA), 38 patients received concurrent chemoradiotherapy
      (CRT) and 47 patients received NA followed by CRT. The median dose of RT was 60
      Gy. Maxillectomy was undertaken in 98 patients. RESULTS: The 5 year overall
      survival (OAS) and local control probability (LCP) were 56.6 and 73.7%,
      respectively. On univariate analysis, surgery (P < 0.0001) and T classification
      (P < 0.04) were significant prognostic factors for OAS and LCP. Histological
      grade and nodal status were also related to OAS. However, any chemotherapy
      sequence was not associated with the treatment outcome. On multivariate analysis,
      surgery (P < 0.0005) and T classification (P < 0.05) were identified as
      significant prognostic factors for LCP and OAS. CONCLUSIONS: This study suggests
      that both surgery and T stage are important prognostic factors for LCP and OAS in
      the management of SCC of the maxillary sinus. The appropriate sequence of
      chemotherapy remains to be elucidated in the future study.

PMID- 16275676
TI  - A randomized phase III trial of post-operative adjuvant oral fluoropyrimidine
      versus sequential paclitaxel/oral fluoropyrimidine; and UFT versus S1 for T3/T4
      gastric carcinoma: the Stomach Cancer Adjuvant Multi-institutional Trial Group
      (Samit) Trial.
AB  - Paclitaxel, S1 and their combined sequential administration is proposed to be
      examined installing UFT as an active control of adjuvant chemotherapy for
      curatively resected T3-4 gastric cancer in a multicenter Phase III trial. The
      primary endpoint is disease-free survival and the secondary endpoints are
      incidence of adverse events, overall survival and compliance. The sample size is
      370 per treatment arm (1480 in total) for two hypotheses of the superiority of
      sequential use of paclitaxel followed by oral fluoropyrimidines to
      fluoropyrimidines (UFT/S1) alone and the non-inferiority of S1 to UFT to be
      tested by two-by-two factorial design. Abdominal CT or US is performed every 3
      months in the first 2 years and every 6 months thereafter for 3 years in total to
      ensure recurrence data collection. This trial could appraise sequential
      combination therapy and efficacy of new drugs as adjuvant for gastric cancer
      treatment.

PMID- 16275678
TI  - Therapeutic effect of topical applications of trichloroacetic acid for vaginal
      intraepithelial neoplasia after hysterectomy.
AB  - OBJECTIVE: We attempted to evaluate the therapeutic effect of trichloroacetic
      acid (TCA) for vaginal intraepithelial neoplasia (VaIN) after hysterectomy and to
      identify factors affecting persistence/recurrence. METHODS: Twenty-eight post
      hysterectomy patients with various grades of VaIN were enrolled in this study
      between January 2001 and December 2003. They were managed with intravaginal 50%
      TCA once weekly for 1-4 weeks, and all patients were followed up every 3 months
      for at least 1 year. Assessments by Papanicolaou smear and colposcopy were
      performed, as was biopsy when indicated during the follow-up period. Cox
      regression analysis was used to identify independent factors predicting
      persistence/recurrence. RESULTS: In 20 of 28 patients (71.4%) VaIN went into
      remission. Treatment success was observed in all 11 patients with VaIN I, whereas
      only 9 out of 17 patients (53%) with VaIN II/III went into remission (P = 0.009).
      Severity of VaIN was the only significant independent predictor of
      persistence/recurrence (odds ratio = 3.5; 95% confidence interval = 1.1, 11.6; P
      = 0.038). The treatment was well tolerated with no major side effects.
      CONCLUSIONS: Based on our findings, 50% TCA was a potential agent with minimal
      side effects for low-grade VaIN. Further prospective controlled study is
      warranted to verify our statements. However, as for high-grade lesions, further
      investigation with different TCA concentration is compelling.

PMID- 16275679
TI  - Acute toxicity and preliminary clinical outcomes of concurrent radiation therapy
      and weekly docetaxel and daily cisplatin for head and neck cancer.
AB  - OBJECTIVE: To examine the feasibility and efficacy of concurrent weekly docetaxel
      and radiation therapy as a definitive treatment for head and neck cancer (HNC).
      METHODS: Thirty-two patients with primary HNC, who were treated with concurrent
      weekly docetaxel and radiation therapy, were analysed. The distribution of the
      disease stage was as follows: Stage II, 18 patients; Stage III, 3 patients; Stage
      IVA, 7 patients; Stage IVB, 3 patients; the patient of cervical lymph node
      metastasis with unknown primary tumor was not assessable. The average total dose
      of radiotherapy was 67.5 Gy. Docetaxel (10 mg/m(2), intravenously, once a week)
      was given to all patients up to four cycles, and cisplatin (6 mg/m(2),
      intravenously, five times a week) was also administered to all patients for up to
      3 weeks from the beginning of the radiation therapy. RESULTS: Only in two
      patients did the radiotherapy need to be temporarily interrupted due to the
      development of acute mucositis. Grade 3 toxicity was observed in six patients.
      Grade 4 acute mucositis was seen in one patient. The response rate was 100%, and
      complete response (CR) was observed in 30 patients (94%). At the time of the
      analysis, the 2 year local control and relapse-free rates in the 30 patients
      showing CR were 90 and 76%, respectively. CONCLUSIONS: Concurrent weekly
      docetaxel and radiation therapy did not affect the compliance of the patients for
      the radiation therapy, indicating that the acute toxicities were within
      acceptable limits.

PMID- 16275680
TI  - Long-term outcomes of 60 Gy conventional radiotherapy combined with androgen
      deprivation for localized or locally advanced prostate cancer.
AB  - BACKGROUND: Until 1998 in Japan, very few institutions were treating prostate
      cancer solely with radiotherapy (RT) >70 Gy and most were using < or =65 Gy in
      combination with hormone therapy. The present study reports the long-term results
      of RT combined with hormone therapy for localized and locally advanced prostate
      cancer. METHODS: We investigated 57 patients who were treated by external beam RT
      plus hormone therapy (median age 79 years, median prostate-specific antigen
      concentration 15.0 ng/ml) between 1992 and 1998. Patients received 40 Gy of
      radiation to the pelvis and an additional 20 Gy as a prostatic boost. Hormone
      therapy was begun on the first day of irradiation and continued thereafter.
      RESULTS: The median follow-up was 93.3 months and the 5 and 10 year actual
      overall survival rates were 67.8 and 32.6%, respectively, with 5 and 10 year
      cause-specific survival rates of 97.9 and 95.0%, respectively. The expected
      survival rate was 66.2% at 5 years, and overall survival was above expected
      survival. Only one patient developed severe proctitis (Grade 3). The 5 year
      occurrence of Grade 1/2 genitourinary toxicity was 23.2%. CONCLUSIONS: Combined
      RT and hormone therapy has a good long-term outcome without severe adverse
      events. The overall survival rate compares well with the expected survival rate.

PMID- 16275681
TI  - In vivo transfer of high-level mupirocin resistance from Staphylococcus
      epidermidis to methicillin-resistant Staphylococcus aureus associated with
      failure of mupirocin prophylaxis.
AB  - OBJECTIVES: We examined the molecular basis of the emergence of mupirocin
      resistance in a methicillin-resistant Staphylococcus aureus (MRSA) strain
      colonizing a nursing home resident undergoing mupirocin prophylaxis. PATIENT AND
      METHODS: A persistent carrier of mupirocin-susceptible MRSA participated in a
      trial of mupirocin for nasal decolonization among nursing home residents. During
      prophylaxis a high-level mupirocin-resistant MRSA emerged in the nasal isolates
      from this patient. S. aureus and coagulase-negative staphylococci were isolated
      prior to, during and after 14 days of mupirocin treatment. The staphylococcal
      isolates and their plasmids were examined by molecular genetic methods. RESULTS:
      All mupirocin-susceptible and -resistant MRSA isolates possessed the same
      genotype. The patient was also colonized by a single mupirocin-resistant
      Staphylococcus epidermidis strain. The mupirocin-resistant MRSA and S.
      epidermidis strains harboured identical plasmids that carried the mupA
      determinant and genes for conjugative DNA transfer in staphylococci. These
      plasmids could be transferred in vitro from both clinical isolates to S. aureus
      RN2677. CONCLUSIONS: The MRSA strain contained a conjugative plasmid expressing
      mupA that was identical with that found in the S. epidermidis strain which
      colonized the patient. These findings suggest that transfer of mupA from S.
      epidermidis to MRSA probably occurred during mupirocin prophylaxis.

PMID- 16275682
TI  - The Macy study: a framework for consensus.

PMID- 16275683
TI  - Knowledge integration and reasoning as a function of instruction in a hybrid
      medical curriculum.
AB  - This study investigates the effect of curricular change on knowledge integration
      and reasoning processes during problem-solving by medical students. The
      curricular change involved the introduction of problem-based, small group
      tutorials into a conventional health science curriculum (CC). Students at three
      levels of training were asked to provide diagnostic explanations of two clinical
      cases, both before (spontaneous) and after (primed) being exposed to basic
      science information relevant to the clinical problems. Data were analyzed using
      techniques of propositional and semantic analysis. Based on theories of
      instruction and cognition, we expected that the instructional changes would
      facilitate knowledge integration and influence the reasoning patterns of the
      students. The results show that students generated fewer inferences and used more
      information from the basic science text (text-based) to explain the clinical
      problems. However, they generated a greater number of elaborations during
      explanations using a mixture of data-driven and hypothesis-driven strategies. The
      spontaneous and primed problem-solving conditions produced more hypothesis-driven
      and data-driven strategies, respectively, as would be expected in a hybrid
      curriculum. We conclude that a) problem-based, small group tutorials facilitate
      integration of clinical and biomedical knowledge through the use of elaborations
      and hypothesis-driven strategies, and b) aspects of problem-based learning can be
      successfully integrated into traditional curricula.

PMID- 16275684
TI  - Post-affirmative action Supreme Court decision: new challenges for academic
      institutions.
AB  - This article describes several aspects of the University of Michigan Supreme
      Court cases regarding diversity in higher education. It provides a number of
      resources that are useful in shaping the rationale and institutional practices
      and policies for admissions and the recruitment and retention of diverse classes
      of students for the health professions.

PMID- 16275685
TI  - Personality as a predictor of professional behavior in dental school: comparisons
      with dental practitioners.
AB  - The purpose of this study was to examine the use of personality measures to
      predict the success of dental students (N = 87) in clinical and academic courses
      and to compare their personality profiles to those of dental practitioners (N =
      130). A second purpose of the study was to develop a new criterion measure, the
      Student Professionalism Scale, based on competencies previously identified as
      necessary for professional success. The Canadian Dental Aptitude Test (DAT)
      predicted first-year, preclinical academic success; the DAT Reading Comprehension
      component predicted third-year clinical performance; and Perceptual Ability, the
      ability to deal with two- and three-dimensional objects, predicted student
      professionalism. Results from the personality measure indicated that
      Conscientiousness and Neuroticism, and to a lesser extent Agreeableness, were
      significant predictors of both first-year academic performance and professional
      behavior. In comparing the personality profiles of dental students to dental
      practitioners, students who were more similar to the dentists did better in their
      first year of coursework. Implications of the findings are discussed in the
      context of the dental admissions process.

PMID- 16275686
TI  - Outcome assessment of the Dental Early Acceptance Program.
AB  - The University of Texas Health Science Center at San Antonio (UTHSCSA) Dental
      School recruits a student body from a wide number of undergraduate institutions,
      primarily in Texas. One method supporting this effort is the Dental Early
      Acceptance Program (DEAP). This program is unique in that it grants conditional
      acceptance to dental school during a student's first year of undergraduate
      education and admission upon completion of three years of college coursework as
      directed by the student's undergraduate academic advisor. The purpose of this
      study was to assess and compare the academic performance of DEAP students to
      students accepted through the standard competitive admissions process. The
      academic records of all students matriculating into our dental school between
      1993 and 1996 were examined. National Board Dental Examination Parts I and II
      scores, the cumulative dental school and college GPAs, DAT scores, and
      demographic data were recorded. The data were analyzed descriptively and
      statistically. Graduation rates were 92 percent for DEAP students and 94 percent
      for standard admissions students. Comparison of college cumulative GPA between
      the two groups showed no statistically significant difference. A significant
      difference was found between the groups in their dental school cumulative GPA. In
      a comparison of National Board Examination scores, DEAP students had a
      significantly lower NBDE Part I mean score (82.9) than standard admissions
      students (85.8). DEAP students also showed significantly lower NBDE Part II
      scores (80.4) than standard admissions students (82.4).

PMID- 16275687
TI  - Stabilization splint therapy for the treatment of temporomandibular myofascial
      pain: a systematic review.
AB  - The aim of this review is to establish the effectiveness of stabilization splint
      (SS) therapy in reducing symptoms in patients with myofascial pain. Searching of
      electronic databases, handsearching of relevant key journals, and screening of
      reference lists of included studies were undertaken. There was no language
      restriction, and unpublished research was sought. The selection criteria were
      randomized controlled trials comparing splint therapy to either no treatment or
      another active treatment. Data extraction and validity assessment were carried
      out independently and in duplicate. Studies were grouped according to treatment
      type. Twenty potentially relevant Randomized Controlled Trials (RCTs) were
      identified. Only twelve met the inclusion criteria. There is insufficient
      evidence either for or against the use of stabilization splint therapy over other
      active interventions for the treatment of temporomandibular myofascial pain.
      However, it appears that stabilization splint therapy may be beneficial for
      reducing pain severity at rest and on palpation and depression when compared to
      no treatment. The authors suggested the need for well conducted RCTs that pay
      attention to method of allocation, blind outcome assessment, sample size, and
      duration of follow-up. Various measures were adopted to assess the outcomes of
      treatment. Standardization of the methods used to measure outcomes of the
      treatment of myofascial pain should be established in future RCTs.

PMID- 16275688
TI  - Utilization of evidence-based informational resources for clinical decisions
      related to posterior composite restorations.
AB  - The purpose of this study was to characterize evidence-based informational
      resources utilization patterns of a sample of general dentists with respect to
      clinical decisions regarding posterior composite restorations. A stratified
      random sample of general practitioners belonging to the Academy of General
      Dentistry (n = 2880) was mailed a questionnaire that elicited information about
      practice characteristics and informational resources used for clinical decision
      making related to posterior composite restorations. Six hundred ninety-nine
      dentists responded (24 percent response rate). Use of evidence-based (EB)
      resources (journals and online data bases) was low for all respondents (14
      percent) for all levels of experience; however, more experienced clinicians were
      more likely to use EB resources than recent graduates. AGD Master-level members
      were significantly more likely to use EB resources than their counterparts (p <
      .05). Within the limitation of this study, current patterns suggest a low
      reliance on evidence-based informational resources in the practice of clinical
      dentistry.

PMID- 16275689
TI  - Dentistry, nursing, and medicine: a comparison of core competencies.
AB  - Health care, including oral health care and oral health education, is under great
      stress in the United States. The cost of and access to care, the cost of dental
      education, and a shortage of educators have led leaders in dental education,
      organized dentistry, and the public sector to underscore the problem. One of the
      proposed solutions is to find synergies and new health care and education models
      by building bridges among the health professions. One potential solution is being
      implemented at the NYU College of Dentistry (NYUCD). Dentistry and nursing are
      seemingly unrelated professions, and they are rarely if ever modeled together.
      That is about to change with the joining together of NYUCD and the Division of
      Nursing of the NYU Steinhardt School of Education in creating a College of
      Nursing within the College of Dentistry. This process has not been without
      controversy. Following the Division of Nursing's request to join NYUCD, and the
      subsequent announcement of the proposed combination by NYU in December 2004, some
      members of the dental profession responded by questioning the appropriateness of
      the merger and the similarity of the two programs. Nevertheless, substantial
      parallels exist in the education and practice of dentists and nurse practitioners
      (NP) including basic, social, and some clinical science education, practice
      models, research synergies, and community service. However, similarities in the
      core competencies of these professions have not been analyzed formally and in
      detail. Accordingly, the purpose of this study was to compare the core
      competencies of nurse practitioner and dental education programs. The results
      show a surprising overlap of the core competencies of the dental and nursing
      professions (38 percent partial or total overlap). A similar overlap with
      medicine also exists, albeit lower (25.4 percent). These results are notable
      because they demonstrate that the three health professions, independently of one
      another, developed very similar basic competencies and learning objectives. These
      data should encourage other health professions programs to seek new collaborative
      models for education, beyond the current silos of training, and new health care
      delivery systems as has been strongly recommended by the Institute of Medicine.
      Such collaborative education redirects health care toward providing truly
      interdisciplinary comprehensive primary care for patients.

PMID- 16275690
TI  - Subsequent dental research output of South African division of the IADR Colgate
      Prize entrants.
AB  - This study recorded the research output of all participants for the IADR (South
      African Division; SA) Colgate Prize for 1967-2004 to establish whether, in their
      later careers, prize winners had a greater research output than runners-up. Using
      a list of all entrants, each individual was classified as winner or runner-up and
      by gender, race, and research field of presentation. The publication output for
      each individual was obtained from PubMed. A Poisson regression set at P < 0.05
      compared publication numbers between winners and runners-up. There were two
      groups of entrants: 101 participated once, and twenty-two participated twice or
      thrice. Winners had significantly more publications than runners-up, more so for
      the multiple entrants (winners 27.5+/-22.4; runners-up 16.5+/-25.5) than single
      entrants (winners 16.0+/-40.8; runners-up 12.0+/-27.7). The number of individuals
      participating in the Colgate Prize has declined, but representivity for race and
      gender is improving. This is the first study to establish that SA IADR Colgate
      Prize participants fulfil the long-term IADR ideal of research promotion among
      young investigators.

PMID- 16275691
TI  - Survey of dental student financial assistance, 2003-04.
AB  - The Survey of Dental Student Financial Assistance reports data collected by the
      American Dental Education Association on financial assistance to dental students
      in the academic year 2003-04. Over 90 percent of students at the fifty-one
      responding dental schools received financial assistance in the form of loans,
      grants, scholarships and/or work-study programs, with students receiving an
      average of 43,191 dollars per year. As tuition and fees rose 21.4 percent over
      the past two years, financial assistance rose 23.1 percent. Both continue to
      increase at a rate greater than inflation. The primary source of financial
      assistance was in the form of loans, accounting for nearly 90 percent of the
      reported financial assistance. Most of the remaining assistance was in the form
      of obligated or unobligated grants and scholarships, with an increasing share
      attributable to grants/scholarships with obligations following graduation. As the
      price of higher education increases, reliance on financial assistance continues
      to increase, and students graduate with an increasing amount of debt in real and
      constant dollars.

PMID- 16275692
TI  - Senior scientists' legacy opportunity.

PMID- 16275693
TI  - Strength factors among women of Mexican descent.
AB  - Whereas few studies with Latina samples include strength factors (resilience,
      mastery, life satisfaction, and perceived energy level) as variables, even fewer
      include strength factors together with acculturation in the same study. As part
      of a larger study, the purpose of this analysis is to describe and examine the
      relationships between strength factors, risk factors such as acculturation and
      substance use, resource factors including financial adequacy and education, and
      the health and illness factor of perceived health status among a convenience
      sample of 315 low-income women of Mexican descent, ages 21 to 40. Cross-sectional
      survey data were collected and analyzed. Results show intragroup differences
      related to the well-being of women of Mexican descent living with low incomes in
      urban settings.

PMID- 16275694
TI  - Medication and dietary compliance beliefs in heart failure.
AB  - Patients with heart failure are required to comply with a medication regimen and
      dietary sodium restrictions. The objectives of this study were to determine the
      most frequently perceived benefits of and barriers to compliance with medication
      and dietary sodium restrictions and evaluate the relevancy of these scale items
      for testing in tailored intervention studies. Data were collected as part of two
      studies that evaluated the psychometric properties of two questionnaires. The
      most frequently identified benefit of medication compliance was decreasing the
      chance of being hospitalized, and the most commonly reported barrier was
      disruption of sleep. Patients were knowledgeable about the benefits of compliance
      with dietary sodium restrictions, and the poor taste of food on the low sodium
      diet was the most common barrier. Heart failure patients perceive benefits of and
      barriers to compliance with therapeutic regimens that are likely to be amenable
      to tailored interventions designed to enhance compliance.

PMID- 16275695
TI  - Practice of health-promoting behaviors by nursing home residents.
AB  - The decade of the '90s witnessed the emergence of health promotion as a national
      priority for all age groups. Despite the fact that Healthy People 2010 identified
      objectives for the nursing home population, little is known about factors that
      promote the practice of health-promoting behaviors by nursing home residents.
      This study examined the separate and combined contributions of personal and
      contextual influences on the practice of health-promoting behaviors by nursing
      home residents. One hundred eighty-four residents and 90 staff members from six
      nursing homes participated in this study. Using a modified version of contextual
      regression analysis, 57.8% of the variance in health-promoting lifestyle (HPL)
      behaviors was explained when all variables were entered into the equation.
      Personal influences explained a significant amount of variation (53.5%) in
      current HPL behaviors. These findings underscore the importance of looking at
      ways to support the efforts of nursing home residents to engage in the practice
      of health-promoting behaviors.

PMID- 16275696
TI  - Supportive relationships and medication adherence in HIV-infected, low-income
      Latinos.
AB  - Inadequate social support and poor communications with health care providers can
      affect adherence to antiretroviral therapy. The magnitude of independent effects
      of these factors on adherence is not fully known. This study examined the
      relationship of perceived emotional or informational social support from family
      and friends, quality of physician-patient communications and relationships, and
      medication adherence in a sample of low-income, Spanish-speaking, HIV-positive
      Latino men and women receiving treatment in community-based clinics (n = 85).
      Results of the study indicated that, whereas emotional or informational support
      was significantly associated with level of dose adherence (OR, 1.04, 95% CI, 1.01
      1.08; p = .03), quality of physician-patient communications or relationships was
      significantly associated with adherence to medication schedule,t(6, 71) = 4.45,p
      < .001. Quality of patient-physician relationship accounted for 22% of the
      variance in adherence to medication schedule. Both kinds of support were
      associated with better adherence in this population but may affect adherence
      behaviors in different ways.

PMID- 16275697
TI  - Nursing structure, processes, and patient outcomes in army medical centers.
AB  - The purpose of this study was to describe patient outcomes in Army Medical
      Centers, identify differences in outcomes between mixed medical-surgical bed and
      specialty intensive care units (ICUs), and explore predictive models for outcomes
      attributable to nursing structure and processes. Data were collected from 138
      patients and 103 nurses in four medical-surgical and four ICUs in two Army
      Medical Centers. Significant differences for unit type were found for length of
      stay and patient satisfaction with nursing care. Outcome predictive models were
      modest (adjusted R2 = .16 to .24) and significant for length of stay,
      satisfaction with nursing care, satisfaction with pain management, and health
      status following discharge. Exploring differences and commonalities between
      military and civilian hospitals will ultimately provide insight into ways of
      improving patient outcomes and bettering the work environment of nurses.

PMID- 16275698
TI  - Hiring the right people and management of research staff.
AB  - Research grant or project management requires substantial skills and experiences
      of the principal investigator and the investigative team. Hiring the right people
      for appropriate positions and ongoing staff training and management are critical
      keys to successful conduct of the research projects. Necessary activities include
      the clear identification of positions and qualifications, recruiting the best,
      and hiring, training, and retaining the right staff. Tips and strategies for
      problem solving during each step are included.

PMID- 16275701
TI  - Postdoctoral research preparation.

PMID- 16275702
TI  - Abuse experiences, perceptions, and associated decisions during the childbearing
      cycle.
AB  - The study purpose was to generate a theoretical understanding of women's
      experiences and perceptions of intimate partner abuse during the childbearing
      cycle. Dimensional analysis, a grounded theory method, was used. Twenty-one
      interviews were conducted with 12 women who were (a) currently in an abusive
      relationship with an intimate male partner and pregnant or postpartum (n = 5) or
      who had (b) experienced abuse by an intimate male partner during a past pregnancy
      or postpartum (n = 7). Disparities between the two concurrent phenomena of abuse
      and pregnancy led women to feel as though they were living two separate lives.
      Pregnancy provided the impetus for reinvesting in the partnered relationship and
      constructing a family. Leaving an abusive relationship was not considered unless
      the partner ended the relationship first or the woman perceived an increased risk
      of danger. Postpartum up to 2 years after birth was a critical transitional time
      for women.

PMID- 16275703
TI  - Teenage mothers at age 30.
AB  - This longitudinal, interpretive study explored how teen mothers experienced the
      self and future during a 12-year period. Sixteen families were first interviewed
      intensively in 1988-1989 once the teen's infant reached age 8 to 10 months; they
      were reinterviewed in 1993, 1997, and 2001 (Time 4). Twenty-seven family members
      were reinterviewed at Time 4. The metaphor of a narrative spine is used to
      describe how the mothers'lives unfolded during the 12-year period. The narrative
      spines of some mothers were large and supported well-developed, coherent
      "chapters" on mothering, adult love, and work. For others, mothering provided a
      "backbone" for a meaningful life; however, chapters on adult love and work were
      less fully developed. The lives of a third group of mothers lacked a coherent
      narrative structure. Each pattern is presented with a paradigm case.

PMID- 16275704
TI  - African American women's coping with health care prejudice.
AB  - African American clients have reported racism and prejudice in health care; yet
      there is limited documentation of the strategies used to cope with these
      experiences. This study describes African American women's perceptions of
      prejudice in health care and the strategies used to cope with the experiences.
      This qualitative study used the constructivist perspective of interpretive
      interactionism for paradigmatic and methodological guidance. Participants were 20
      women ranging from age 26 to 74 years with 50% having a high school education.
      Individual interviews consisting of five areas were conducted with three
      instruments measuring ethnic identity, socioeconomic status, and general
      demographics. The analyses provide two themes: experience with the "White health
      care system" and strategies for coping with the prejudice, which included getting
      angry, learning to unlearn, being assertive, and walking away. Consistent with
      the discussions of race in the United States, racism in health care has become a
      subtle entity that infuses health care relationships.

PMID- 16275706
TI  - The phenomenology of deciding about hemodialysis among Taiwanese.
AB  - The purpose of this study was to describe the experience of making hemodialysis
      choices among Taiwanese with end-stage renal disease (ESRD). Using Colaizzi's
      phenomenological method, 12 ESRD patients provided in-depth, audiotaped
      interviews that were then transcribed and analyzed. The results of the data
      analysis revealed three broad categories and ten themes. The first category,
      confronting the dialysis treatment, included four themes: fear caused by false
      beliefs, a sense of threat to life, concern about the impairment of self-concept,
      and fear of physical limitations. The second category, seeking further
      information, included three themes: getting opinions of family members, seeking
      professional confirmation, and exploring alternative treatments. The third
      category, living with dialysis, included three themes: worsening symptoms,
      support of the family, and law of causation. These categories and themes revealed
      the difficulties that ESRD patients dealt with and the influence these
      difficulties and their culture had on the treatment choice.

PMID- 16275705
TI  - Predictors of perceived health status of tuberculosis-infected homeless.
AB  - This study examines the predictors of perceived health status among homeless
      adults with latent tuberculosis (TB) in Los Angeles, especially in relation to
      gender differences. Total, 415 men and women enrolled in a TB-adherence trial
      completed baseline assessments concerning health status. Results indicated that
      women were more likely than men to report being in fair or poor health and to
      have experienced health problems. More women than men self-reported daily drug
      use and poor mental health. Homeless women were also more likely than their male
      counterparts to receive support from non-drug-users. Homeless adults who reported
      fair or poor health were also more likely than those who reported better health
      to have used injection drugs, to report experiencing depressive symptoms and poor
      mental health, and to have been homeless more than 3 years. Predictors of fair or
      poor health included being female and experiencing more depressive symptoms.

PMID- 16275707
TI  - Biological consequences of trinuclear platinum complexes: comparison of [[trans
      PtCl(NH3)2]2mu-(trans-Pt(NH3)2(H2N(CH2)6-NH2)2)]4+ (BBR 3464) with its
      noncovalent congeners.
AB  - [[trans-PtCl(NH(3))(2)](2)mu-(trans-Pt(NH(3))(2)(H(2)N(CH(2))(6)NH(2))(2))](4+)
      (BBR 3464) is a 4+ cationic trinuclear platinum drug that has undergone phase II
      clinical trials in the treatment of ovarian and lung cancers. The chemical
      structure of BBR 3464 is distinct from that of clinically used agents such as
      cisplatin and oxaliplatin. As a consequence, the modes of DNA binding and the
      structures of BBR 3464 DNA adducts are also structurally distinct from those
      formed by cisplatin and oxaliplatin. Previous chemical and spectroscopic
      measurements on BBR 3464 had elucidated a significant noncovalent contribution to
      DNA binding. To examine this effect further, the biological activity of two BBR
      3464 analogs that bind DNA only through noncovalent interactions was investigated
      in this study, and their cellular effects were compared with those caused by the
      "parent" drug. The compounds were [[trans-PtL(NH(3))(2)](2)mu-(trans
      Pt(NH(3))(2)(H(2)N(CH(2))(6)NH(2))(2))](n+), with L = NH(3), n = 6 for compound
      I, and L = H(2)N(CH(2))(6)NH(3), n = 8 for compound II. All compounds induce
      caspase-dependent apoptosis in both primary mast cells and transformed
      mastocytomas, although with a smaller IC(50) value in the transformed cells. In
      cells deficient in either the tumor suppressor proteins p53 or Bax, apoptosis was
      least affected in the case of II, but in all cases the effect of p53 deficiency
      was greater than that of Bax. Surprisingly, cellular uptake was actually enhanced
      for the more highly charged compounds, resulting in significant (micromolar)
      cyotoxicity for II. Cellular accumulation was enhanced in mastocytomas over
      primary mast cells, suggesting a mechanism for enhancement of tumor cell
      selectivity.

PMID- 16275708
TI  - Phosphorus workshop.

PMID- 16275709
TI  - Dietary strategies for reduced phosphorus excretion and improved water quality.
AB  - Cost effective feeding strategies are essential to deal with P surpluses
      associated with intensive animal agriculture and the consequent impact on water
      quality. Reduction of P overfeeding, use of feed additives to enhance dietary P
      utilization, and development of high available phosphorus (HAP) grains have all
      been shown to decrease fecal P excretion without impairing animal performance.
      Much progress has been made, but more research will be needed to refine these
      strategies to maximize reductions in P excretion while maintaining animal
      performance. Recent research has focused on the impact of modifying dietary P on
      the forms of P excreted and the mobility of P in soils amended with these
      manures, with strong treatment trends becoming evident in the literature. In
      general, dietary strategies have been developed that can effectively reduce the
      total P concentration in manures produced, and combining strategies usually leads
      to greater reductions than individual practices. However, the impact of different
      approaches on the solubility of P in manures and amended soils has been more
      variable. Soluble P remains of particular concern due to links between solubility
      of P in manure and P losses from manure-amended soils. In this paper, we outline
      the major strategies for reducing dietary P in different species, review the
      literature on the impact of these approaches on P forms in manures and amended
      soils, and discuss the potential beneficial effects on animal agriculture and the
      environment.

PMID- 16275710
TI  - Long-term effects of poultry litter, alum-treated litter, and ammonium nitrate on
      aluminum availability in soils.
AB  - Research has shown that alum [Al(2)(SO(4))(3).14H(2)O] applications to poultry
      litter can greatly reduce phosphorus (P) runoff, as well as decrease ammonia
      (NH(3)) volatilization. However, the long-term effects of fertilizing with alum
      treated litter are unknown. The objectives of this study were to evaluate the
      long-term effects of normal poultry litter, alum-treated litter, and ammonium
      nitrate (NH(4)NO(3)) on aluminum (Al) availability in soils, Al uptake by tall
      fescue (Festuca arundinacea Schreb.), and tall fescue yields. A long-term study
      was initiated in April of 1995. There were 13 treatments (unfertilized control,
      four rates of normal litter, four rates of alum-treated litter, and four rates of
      NH(4)NO(3)) in a randomized block design. All fertilizers were broadcast applied
      to 52 small plots (3.05 x 1.52 m) cropped to tall fescue annually in the spring.
      Litter application rates were 2.24, 4.49, 6.73, and 8.98 Mg ha(-1) (1, 2, 3, and
      4 tons acre(-1)); NH(4)NO(3) rates were 65, 130, 195, and 260 kg N ha(-1) and
      were based on the amount of N applied with alum-treated litter. Soil pH,
      exchangeable Al (extracted with potassium chloride), Al uptake by fescue, and
      fescue yields were monitored periodically over time. Ammonium nitrate
      applications resulted in reductions in soil pH beginning in Year 3, causing
      exchangeable Al values to increase from less than 1 mg Al kg(-1) soil in Year 2
      to over 100 mg Al kg(-1) soil in Year 7 for many of the NH(4)NO(3) plots. In
      contrast, normal and alum-treated litter resulted in an increase in soil pH,
      which decreased exchangeable Al when compared to unfertilized controls. Severe
      yield reductions were observed with NH(4)NO(3) beginning in Year 6, which were
      due to high levels of acidity and exchangeable Al. Aluminum uptake by forage and
      Al runoff from the plots were not affected by treatment. Fescue yields were
      highest with alum-treated litter (annual average = 7.36 Mg ha(-1)), followed by
      normal litter (6.93 Mg ha(-1)), NH(4)NO(3) (6.16 Mg ha(-1)), and the control
      (2.89 Mg ha(-1)). These data indicate that poultry litter, particularly alum
      treated litter, may be a more sustainable fertilizer than NH(4)NO(3).

PMID- 16275711
TI  - Use of drinking water treatment residuals as a potential best management practice
      to reduce phosphorus risk index scores.
AB  - The P risk index system has been developed to identify agricultural fields
      vulnerable to P loss as a step toward protecting surface water. Because of their
      high Langmuir phosphorus adsorption maxima (P(max)), use of drinking water
      treatment residuals (WTRs) should be considered as a best management practice
      (BMP) to lower P risk index scores. This work discusses three WTR application
      methods that can be used to reduce P risk scores: (i) enhanced buffer strip, (ii)
      incorporation into a high soil test phosphorus (STP) soil, and (iii) co-blending
      with manure or biosolids. The relationship between WTR P(max) and reduction in P
      extractability and runoff P was investigated. In a simulated rainfall experiment,
      using a buffer strip enhanced with 20 Mg WTR ha(-1), runoff P was reduced by from
      66.8 to 86.2% and reductions were related to the WTR P(max). When 25 g kg(-1) WTR
      was incorporated into a high STP soil of 315 mg kg(-1) determined using Mehlich-3
      extraction, 0.01 M calcium chloride-extractable phosphorus (CaCl(2)-P) reductions
      ranged from 60.9 to 96.0% and were strongly (P < 0.01) related to WTR P(max). At
      a 100 g kg(-1) WTR addition, Mehlich 3-extractable P reductions ranged from 41.1
      to 86.7% and were strongly (P < 0.01) related to WTR P(max). Co-blending WTR at
      250 g kg(-1) to manure or biosolids reduced CaCl(2)-P by >75%. The WTR P(max)
      normalized across WTR application rates (P(max) x WTR application) was
      significantly related to reductions in CaCl(2)-P or STP. Using WTR as a P risk
      index modifying factor will promote effective use of WTR as a BMP to reduce P
      loss from agricultural land.

PMID- 16275712
TI  - Using gypsum to reduce phosphorus in runoff from subcatchments in South
      Australia.
AB  - Concentrations of phosphorus (P) in runoff from agricultural catchments in
      southern Australia are high and well above national and international limits.
      Phosphorus was found to exit two subcatchments of 3.6 and 4.2 ha in the Adelaide
      hills via both overland flow and interflow. The subcatchments had texture
      contrast soils with high inputs of superphosphate and were openly grazed by
      cattle all year. Interflow at the boundary of the B and C soil horizons accounted
      for as much as half the total water flow that was measured (overland flow, A-B
      interflow, and B-C interflow). The average flow-weighted concentration of total P
      within overland flow was as high as 0.25 mg L(-1), and 0.05 mg L(-1) in B-C
      interflow. In most years P loss was in the dissolved (<0.45 microm) form. In some
      years, interflow was the major pathway for P loss off these catchments. The B-C
      interflow cannot be discounted when searching for management options to reduce P
      loss from texture-contrast soils to waterways. Preliminary laboratory experiments
      showed promise that gypsum could modify agricultural soils and reduce the
      concentrations of P (and dissolved organic C) in runoff before it enters public
      water supply reservoirs. In this study, gypsum, applied at a rate of 15 Mg ha(-1)
      to the 4.2-ha subcatchment, substantially modified the soil chemistry, and
      thereby soil structure. The size and stability of structural aggregates increased
      markedly and this change affected not only the A but also the upper B horizons,
      to a profile depth of approximately 50 cm. However, the impact of these
      physicochemical changes on P concentrations in runoff was not marked. Average
      profile P concentrations were only slightly lower in the runoff from the
      subcatchment following treatment. The high subsoil macroporosity of the gypsum
      treated subcatchment caused an increase in the proportion of runoff by interflow.

PMID- 16275714
TI  - Can constructed wetlands reduce the diffuse phosphorus loads to eutrophic water
      in cold temperate regions?
AB  - Construction of wetlands is a possible supplement to best management practices
      (BMP) at the field level to mitigate phosphorus (P) pollution from agricultural
      areas. In this paper, annual results from 17 intensively studied wetlands in the
      cold temperate or boreal climatic zone are reported and analyzed. Surface areas
      varied from 0.007 to 8.7% of the catchment area. The average total phosphorus
      (TP) retention varied from 1 to 88%, and the dissolved reactive phosphorus (DRP)
      retention from -19 to 89%. Retention varied substantially from site to site,
      indicating the existence of site-specific factors in the catchment and wetlands
      that influenced the P removal. Factors important for P retention in wetlands were
      evaluated through multiple statistical analyses by dividing P into two fractions:
      particulate phosphorus (PP) and DRP. Both relative (%) PP and DRP retention
      increased with wetland surface area. However, PP retention was not as sensitive
      as DRP in terms of wetland size and retention: specific PP retention (gram P
      retention per m(2) and year) decreased as wetland area (A(w)) increased,
      suggesting the existence of a site-specific optimal wetland to catchment area
      (A(c)) ratio. Particulate P retention decreased with increasing DRP to TP ratio,
      while the opposite was found for DRP. Dissolved reactive P retention was higher
      in new than in old wetlands, while increasing age did not influence PP retention
      negatively. Effective BMP in the catchment is important to keep the P loss low,
      because the outlet concentration of P from wetlands is often positively
      correlated to the input concentration. However, wetlands act as the last buffer
      in a catchment, since the retention often increases as the P concentration in
      streams increases.

PMID- 16275713
TI  - Phosphorus losses from agricultural areas in river basins: effects and
      uncertainties of targeted mitigation measures.
AB  - In this paper we show the quantitative and relative importance of phosphorus (P)
      losses from agricultural areas within European river basins and demonstrate the
      importance of P pathways, linking agricultural source areas to surface water at
      different scales. Agricultural P losses are increasingly important for the P
      concentration in most European rivers, lakes, and estuaries, even though the
      quantity of P lost from agricultural areas in European catchments varies at least
      one order of magnitude (<0.2 kg P ha(-1) to >2.1 kg P ha(-1)). We focus on the
      importance of P for the implementation of the EU Water Framework Directive and
      discuss the benefits, uncertainties, and side effects of the different targeted
      mitigation measures that can be adopted to combat P losses from agricultural
      areas in river basins. Experimental evidence of the effects of some of the main
      targeted mitigation measures hitherto implemented is demonstrated, including: (i)
      soil tillage changes, (ii) treatment of soils near ditches and streams with iron
      to reduce P transport from source areas to surface waters, (iii) establishment of
      buffer zones for retaining P from surface runoff, (iv) restoration of river
      floodplain systems to allow natural inundation of riparian areas and deposition
      of P, and (v) inundation of riparian areas with tile drainage water for P
      retention. Furthermore, we show how river basin managers can map and analyze the
      extent and importance of P risk areas, exemplified by four catchments differing
      in size in Norway, Denmark, and the Netherlands. Finally, we discuss the factors
      and mechanisms that may delay and/or counteract the responses of mitigation
      measures for combating P losses from agricultural areas when monitored at the
      catchment scale.

PMID- 16275715
TI  - Rhizosphere conference.

PMID- 16275716
TI  - Root exudation, phosphorus acquisition, and microbial diversity in the
      rhizosphere of white lupine as affected by phosphorus supply and atmospheric
      carbon dioxide concentration.
AB  - White lupine (Lupinus albus L.) was used as a phosphorus (P)-efficient model
      plant to study the effects of elevated atmospheric CO(2) concentrations on (i) P
      acquisition, (ii) the related alterations in root development and rhizosphere
      chemistry, and (iii) the functional and structural diversity of rhizosphere
      microbial communities, on a P-deficient calcareous subsoil with and without
      soluble P fertilization. In both +P (80 mg P kg(-1)) and -P treatments (no added
      P), elevated CO(2) (800 micromol mol(-1)) increased shoot biomass production by
      20 to 35% and accelerated the development of cluster roots, which exhibit
      important functions in chemical mobilization of sparingly soluble soil P sources.
      Accordingly, cluster root formation was stimulated in plants without P
      application by 140 and 60% for ambient and elevated CO(2) treatments,
      respectively. Intense accumulation of citrate and increased activities of acid
      and alkaline phosphatases, but also of chitinase, in the rhizosphere were mainly
      confined to later stages of cluster root development in -P treatments. Regardless
      of atmospheric CO(2) concentrations, there was no significant effect on
      accumulation of citrate or on selected enzyme activities of C, N, and P cycles in
      the rhizosphere of individual root clusters. Discriminant analysis of selected
      enzyme activities revealed that mainly phosphatase and chitinase contributed to
      the experimental variance (81.3%) of the data. Phosphatase and chitinase
      activities in the rhizosphere might be dominated by the secretion from cluster
      roots rather than by microbial activity. Alterations in rhizosphere bacterial
      communities analyzed by denaturing gradient gel electrophoresis (DGGE) were
      related with the intense changes in root secretory activity observed during
      cluster root development but not with elevated CO(2) concentrations.

PMID- 16275717
TI  - Rhizospheric mobilization and plant uptake of radiocesium from weathered micas:
      I. Influence of potassium depletion.
AB  - Potassium depletion in the soil solution around plant roots promotes the root
      uptake of radiocesium. However, it can also induce the transformation of mica
      through the release of interlayer K. In bulk soil, the formation of frayed edge
      sites (FES) with a high selectivity for Cs adsorption is usually related with
      mica weathering. We studied the effect of K level in the nutrient solution on the
      root-induced weathering of phlogopite as well as on the root uptake of
      radiocesium by willow (Salix viminalis L. var. Orm). The willows were grown for 7
      wk in column lysimeters filled with a quartz-phlogopite mixed substrate
      continuously irrigated with nutrient solutions differing in K concentration (0-2
      mM). From a potassium supply of 0.4 mM downward, we observed a decrease in root
      uptake of potassium as well as an increase in (i) potassium release from
      phlogopite, (ii) degree of transformation of phlogopite into vermiculite, and
      (iii) root uptake of radiocesium. Increasing K depletion had thus two effects: a
      decrease of the root uptake of potassium and an increase of phlogopite weathering
      in the rhizosphere, both of which promoted the root uptake of radiocesium.

PMID- 16275718
TI  - Rhizospheric mobilization and plant uptake of radiocesium from weathered micas:
      II. Influence of mineral alterability.
AB  - Acute K depletion in the rhizosphere can lead to increased root uptake of
      radiocesium. Two processes can govern this increase: the very low uptake of
      potassium and the weathering of Cs-fixing clay minerals. Their respective
      importance is, however, unknown. We investigated the effects of these processes
      on radiocesium mobilization by roots of willow (Salix viminalis L.) from three
      micas: muscovite, biotite, and phlogopite. Willows were grown in a mixed quartz
      mica substrate with the three respective (134)Cs-contaminated micas as sole
      sources of potassium and radiocesium. After 7 wk of plant growth, the micas were
      partially weathered. The degree of mica weathering and the prevalent potassium
      concentration in the solution increased in the order muscovite (5-11 microM K) <
      biotite (25-32 microM K) < phlogopite (25-35 microM K). The mobilization and root
      uptake of radiocesium were negligible with muscovite but increased in the same
      order. These results show that mica weathering directly and chiefly governs the
      mobility of radiocesium in K-depleted rhizosphere soil. The low mobility of trace
      Cs in the muscovite rhizosphere is linked with the dioctahedral character of this
      mica, and hence to its very low alterability.

PMID- 16275719
TI  - Mycorrhizae increase arsenic uptake by the hyperaccumulator Chinese brake fern
      (Pteris vittata L.).
AB  - Chinese brake fern (Pteris vittata L.) is a hyperaccumulator of arsenic (As) that
      grows naturally on soils in the southern United States. It is reasonable to
      expect that mycorrhizal symbiosis may be involved in As uptake by this fern. This
      is because arbuscular mycorrhizal (AM) fungi have a well-documented role in
      increasing plant phosphorus (P) uptake, P and As have similar chemical
      properties, and ferns are known to be colonized by AM fungi. We conducted a
      factorial greenhouse experiment with three levels of As (0, 50, and 100 mg kg(
      1)) and P (0, 25, and 50 mg kg(-1)) and with and without Chinese brake fern
      colonized by a community of AM fungi from an As-contaminated site. We found that
      the AM fungi not only tolerated As amendment, but their presence increased frond
      dry mass at the highest As application rate. Furthermore, the AM fungi increased
      As uptake across a range of P levels, while P uptake was generally increased only
      when there was no As amendment. These data indicate that AM fungi have an
      important role in arsenic accumulation by Chinese brake fern. Therefore, to
      effectively phytoremediate As-contaminated soils, the mycorrhizal status of ferns
      needs to be taken into account.

PMID- 16275720
TI  - Effect of corn root exudates on the degradation of atrazine and its chlorinated
      metabolites in soils.
AB  - DIMBOA (3,4-dihydro-2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one), a major
      benzoxazinone of Poaceae plants, was isolated and purified from corn seedlings.
      The effect of isolated and purified DIMBOA on the degradation of atrazine [2
      chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine], and its toxic breakdown
      products, desethylatrazine [2-chloro-4-amino-6-(isopropylamino)-s-triazine; DEA]
      and desisopropylatrazine [2-chloro-4-(ethylamino)-6-amino-s-triazine; DIA], was
      studied in the absence of plants using batch experiments, while the effect of
      corn root exudates on these compounds was determined in hydroponic experiments.
      Degradation experiments were performed in the presence and absence of 50 microM,
      1 mM, or 5 mM DIMBOA resulting in ratios of DIMBOA to pesticide of 1:1, 20:1, and
      100:1. We observed a 100% degradation of atrazine to hydroxyatrazine within 48 h
      at a ratio of DIMBOA to atrazine of 100:1. DIMBOA had the largest effect on
      atrazine, while it was about three times less effective on DEA and DIA. Corn (Zea
      mays L. cv. LG 2185) was exposed to 10 mg L(-1) of either atrazine, DEA, or DIA
      for 11 d in a growth chamber experiment. Up to 4.3 micromol L(-1) d(-1) of
      hydroxyatrazine were formed in the nutrient solutions by plants exposed to
      atrazine, while the formation of hydroxylated metabolites from plants exposed to
      DEA and DIA was smaller and also delayed. The formation of hydroxylated
      metabolites increased in the solution with plant age in all atrazine, DEA, and
      DIA treatments. HMBOA (3,4-dihydro-2-hydroxy-7-methoxy-2H-1,4-benzoxazin-3-one),
      the lactam precursor of DIMBOA, and a tentatively identified derivative of MBOA
      (2,3-dihydro-6-methoxy-benzoxazol-2-one) were detected in the corn root exudates.
      Mass balance calculations revealed that up to 30% of the disappearance of
      atrazine and DEA, and up to 10% of DIA removal from the solution medium in our
      study could be explained by the formation of hydroxylated metabolites in the
      solution itself. Our results show that higher plants such as corn have the
      potential to promote the hydrolysis of triazine residues in soils by exudation of
      benzoxazinones.

PMID- 16275721
TI  - Predicting soil fumigant air concentrations under regional and diverse agronomic
      conditions.
AB  - SOFEA (SOil Fumigant Exposure Assessment system; Dow AgroSciences, Indianapolis,
      IN) is a new stochastic numerical modeling tool for evaluating and managing human
      inhalation exposure potential associated with the use of soil fumigants. SOFEA
      calculates fumigant concentrations in air arising from volatility losses from
      treated fields for large agricultural regions using multiple transient source
      terms (treated fields), geographical information systems (GIS) information,
      agronomic specific variables, user-specified buffer zones, and field reentry
      intervals. A modified version of the USEPA Industrial Source Complex Short Term
      model (ISCST3) is used for air dispersion calculations. Weather information,
      field size, application date, application rate, application type, soil
      incorporation depth, pesticide degradation rates in air, tarp presence, field
      retreatment, and other sensitive parameters are varied stochastically using Monte
      Carlo techniques to mimic region and crop specific agronomic practices. Regional
      land cover, elevation, and population information can be used to refine source
      placement (treated fields), dispersion calculations, and risk assessments. This
      paper describes the technical algorithms of SOFEA and offers comparisons of
      simulation predictions for the soil fumigant 1,3-dichloropropene (1,3-D) to
      actual regional air monitoring measurements from Kern, California. Comparison of
      simulation results to daily air monitoring observations is remarkable over the
      entire concentration distribution (average percent deviation of 44% and model
      efficiency of 0.98), especially considering numerous inputs such as
      meteorological conditions for SOFEA were unavailable and approximated by
      neighboring regions. Both current and anticipated and/or forecasted fumigant
      scenarios can be simulated using SOFEA to provide risk managers and product
      stewards the necessary information to make sound regulatory decisions regarding
      the use of soil fumigants in agriculture.

PMID- 16275722
TI  - Biotic and abiotic degradation of CL-20 and RDX in soils.
AB  - The caged cyclic nitramine 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12
      hexaazaisowurtzitane (CL-20) is a new explosive that has the potential to replace
      existing military explosives, but little is known about its environmental
      toxicity, transport, and fate. We quantified and compared the aerobic
      environmental fate of CL-20 to the widely used cyclic nitramine explosive
      hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in surface and subsurface soil
      microcosms. Soil-free controls and biologically attenuated soil controls were
      used to separate abiotic processes from biologically mediated processes. Both
      abiotic and biological processes significantly degraded CL-20 in all soils
      examined. Apparent abiotic, first-order degradation rates (k) for CL-20 were not
      significantly different between soil-free controls (0.018 < k < 0.030 d(-1)) and
      biologically attenuated soil controls (0.003 < k < 0.277 d(-1)). The addition of
      glucose to biologically active soil microcosms significantly increased CL-20
      degradation rates (0.068 < k < 1.22 d(-1)). Extents of mineralization of (14)C-CL
      20 to (14)CO(2) in biologically active soil microcosms were 41.1 to 55.7%,
      indicating that the CL-20 cage was broken, since all carbons are part of the
      heterocyclic cage. Under aerobic conditions, abiotic degradation rates of RDX
      were generally slower (0 < k < 0.032 d(-1)) than abiotic CL-20 degradation rates.
      In biologically active soil microcosms amended with glucose aerobic RDX
      degradation rates varied between 0.010 and 0.474 d(-1). Biodegradation was a key
      factor in determining the environmental fate of RDX, while a combination of
      biotic and abiotic processes was important with CL-20. Our data suggest that CL
      20 should be less recalcitrant than RDX in aerobic soils.

PMID- 16275723
TI  - Soil chemical changes resulting from irrigation with water co-produced with
      coalbed natural gas.
AB  - Land application of coalbed natural gas (CBNG) co-produced water is a popular
      management option within northwestern Powder River Basin (PRB) of Wyoming. This
      study evaluated the impacts of land application of CBNG waters on soil chemical
      properties at five sites. Soil samples were collected from different depths (0-5,
      5-15, 15-30, 30-60, 60-90, and 90-120 cm) from sites that were irrigated with
      CBNG water for 2 to 3 yr and control sites. Chemical properties of CBNG water
      used for irrigation on the study sites indicate that electrical conductivity of
      CBNG water (EC(w)) and sodium adsorption ratio of CBNG water (SAR(w)) values were
      greater than those recommended for irrigation use on the soils at the study
      sites. Soil chemical analyses indicated that electrical conductivity of soil
      saturated paste extracts (EC(e)) and sodium adsorption ratio of soil saturated
      paste extracts (SAR(e)) values for irrigated sites were significantly greater (P
      < 0.05) than control plots in the upper 30-cm soil depths. Mass balance
      calculations suggested that there has been significant buildup of Na in irrigated
      soils due to CBNG irrigation water as well as Na mobilization within the soil
      profiles. Results indicate that irrigation with CBNG water significantly impacts
      certain soil properties, particularly if amendments are not properly utilized.
      This study provides information for better understanding changes in soil
      properties due to land application of CBNG water. These changes must be
      considered in developing possible criteria for preserving fragile PRB ecosystems.

PMID- 16275724
TI  - Relative movement and soil fixation of soluble organic and inorganic phosphorus.
AB  - There is considerable concern about pollution of surface waters with P. Although
      most of the research has focused on inorganic P in surface runoff, it has
      recently become possible to easily follow the fate of soluble organic P forms in
      soils and waters. Two experiments were performed to compare the relative mobility
      and soil fixation affinity of orthophosphate monoesters, orthophosphate diesters,
      and soluble inorganic P. We used three P substrates, 4-methylumbelliferyl
      phosphate (MUP), deoxyribonucleic acid (DNA), and KH(2)PO(4) in (i) a soil column
      experiment and (ii) a soil P adsorption test tube experiment. Shortly after
      columns were prepared, approximately two pore volumes of 0.005 M CaCl(2) were
      passed through 25 cm length columns containing 10 cm of loamy sand amended with
      approximately 10 mg P as MUP, DNA, or KH(2)PO(4) above 15 cm of nonamended loamy
      sand. The total net quantity of 757.8 microg P 2L(-1) of orthophosphate diesters
      in the leachate from the DNA columns exceeded the net quantity of orthophosphate
      monoesters in leachate from the MUP columns (4.6 microg P 2L(-1)) and soluble
      inorganic P from the KH(2)PO(4) columns (34.0 microg P 2L(-1)). Adsorption of
      soluble organic and inorganic P in the test tube experiment yielded similar
      results: DNA, containing orthophosphate diesters, had a relatively low affinity
      for soils. In both experiments, high concentrations of other P compounds were
      identified in samples treated with organic P substrates, suggesting enzymatic
      hydrolysis by native soil phosphatase enzymes. These findings indicate that
      repeated application of organic forms of P could lead to significant leaching of
      P to ground water.

PMID- 16275725
TI  - Volunteer revegetation of waste rock surfaces at the Bingham Canyon Mine, Utah.
AB  - Voluntary recolonization of sulfide-bearing waste rock dumps by native vegetation
      is inhibited by the harsh chemical and physical conditions. The success of
      volunteer vegetation on the waste rock surfaces at the Bingham Canyon (Utah)
      porphyry copper deposit is most strongly dependent on the soil pH and salinity,
      and to a lesser extent on physical characteristics such as compaction and
      distance from seed source. Vegetation cover and richness both decline below a
      paste pH of about 6 and above a paste conductivity of about 0.7 dS/m (for a 1:1
      soil to water mixture). No significant vegetation establishment occurs below a
      soil pH of about 4.5. Young sulfide-bearing waste rock surfaces at Bingham Canyon
      have high salinity, but as reactive pyrite is depleted and salts are flushed from
      the soil, the salinity eventually declines, allowing volunteer native vegetation
      to become established on surfaces with a circumneutral pH. Under natural
      conditions, the pH of older acidic weathered surfaces will recover very slowly,
      but it can be rapidly raised by adding relatively small amounts of limestone
      because there are few intact reactive sulfides. For uncompacted waste rock
      surfaces with favorable chemical conditions, less than 90% gravel content, and
      that are located near a native seed source, the arithmetic mean volunteer
      vegetation cover was 56 +/- 24% and the mean species richness was 17 +/- 5. These
      data indicate that with adequate surface preparation and limestone addition,
      direct planting of older, acidic, but low salinity waste rock surfaces can
      greatly accelerate natural revegetation.

PMID- 16275726
TI  - In situ measurements of nitrate leaching implicate poor nitrogen and irrigation
      management on sandy soils.
AB  - Minimizing the risk of nitrate contamination along the waterways of the U.S.
      Great Plains is essential to continued irrigated corn production and quality
      water supplies. The objectives of this study were to quantify nitrate (NO(3))
      leaching for irrigated sandy soils (Pratt loamy fine sand [sandy, mixed, mesic
      Lamellic Haplustalfs]) and to evaluate the effects of N fertilizer and irrigation
      management strategies on NO(3) leaching in irrigated corn. Two irrigation
      schedules (1.0x and 1.25x optimum) were combined with six N fertilizer treatments
      broadcast as NH(4)NO(3) (kg N ha(-1)): 300 and 250 applied pre-plant; 250 applied
      pre-plant and sidedress; 185 applied pre-plant and sidedress; 125 applied pre
      plant and sidedress; and 0. Porous-cup tensiometers and solution samplers were
      installed in each of the four highest N treatments. Soil solution samples were
      collected during the 2001 and 2002 growing seasons. Maximum corn grain yield was
      achieved with 125 or 185 kg N ha(-1), regardless of the irrigation schedule (IS).
      The 1.25x IS exacerbated the amount of NO(3) leached below the 152-cm depth in
      the preplant N treatments, with a mean of 146 kg N ha(-1) for the 250 and 300 kg
      N preplant applications compared with 12 kg N ha(-1) for the same N treatments
      and 1.0x IS. With 185 kg N ha(-1), the 1.25x IS treatment resulted in 74 kg N ha(
      1) leached compared with 10 kg N ha(-1) for the 1.0x IS. Appropriate irrigation
      scheduling and N fertilizer rates are essential to improving N management
      practices on these sandy soils.

PMID- 16275727
TI  - Cadmium, copper, nickel, and zinc availability in a biosolids-amended piedmont
      soil years after application.
AB  - Concerns over the possible increase in phytoavailability of biosolids-applied
      trace metals to plants have been raised based on the assumption that
      decomposition of applied organic matter would increase phytoavailability. The
      objectives of this study were to assess the effect of time on chemical
      extractability and concentration of Cd, Cu, Ni, and Zn in plants on plots
      established by a single application of biosolids with high trace metals content
      in 1984. Biosolids were applied to 1.5 by 2.3 m confined plots of a Davidson clay
      loam (clayey, kaolinitic, thermic Rhodic Kandiudults) at 0, 42, 84, 126, 168, and
      210 Mg ha(-1). The highest biosolids application supplied 4.5, 760, 43, and 620
      kg ha(-1) of Cd, Cu, Ni, and Zn, respectively. Radish (Raphanus sativus L.),
      romaine lettuce (Lactuca sativa L. var. longifolia), and barley (Hordeum vulgare
      L.) were planted at the site for 3 consecutive years, 17 to 19 yr after biosolids
      application. Extractable Cd, Cu, Ni, and Zn (as measured by DTPA, CaCl(2,) and
      Mehlich-1) were determined on 15-cm depth samples from each plot. The DTPA
      extractable Cu and Zn decreased by 58 and 42%, respectively, 17 yr after
      application despite a significant reduction in organic matter content. Biosolids
      treatments had no significant effect on crop yield. Plant tissue metal
      concentrations increased with biosolids rate but were within the normal range of
      these crops. Trace metal concentrations in plants generally correlated well with
      the concentrations extracted from soil with DTPA, CaCl(2), and Mehlich-1. Metal
      concentrations in plant tissue exhibited a plateau response in most cases. The
      uptake coefficient values generated for the different crops were in agreement
      with the values set by the Part 503 Rule.

PMID- 16275728
TI  - Spatial variability of soil phosphorus in relation to the topographic index and
      critical source areas: sampling for assessing risk to water quality.
AB  - A measure of soil P status in agricultural soils is generally required for
      assisting with prediction of potential P loss from agricultural catchments and
      assessing risk for water quality. The objectives of this paper are twofold: (i)
      investigating the soil P status, distribution, and variability, both spatially
      and with soil depth, of two different first-order catchments; and (ii)
      determining variation in soil P concentration in relation to catchment topography
      (quantified as the "topographic index") and critical source areas (CSAs). The
      soil P measurements showed large spatial variability, not only between fields and
      land uses, but also within individual fields and in part was thought to be
      strongly influenced by areas where cattle tended to congregate and areas where
      manure was most commonly spread. Topographic index alone was not related to the
      distribution of soil P, and does not seem to provide an adequate indicator for
      CSAs in the study catchments. However, CSAs may be used in conjunction with soil
      P data for help in determining a more "effective" catchment soil P status. The
      difficulties in defining CSAs a priori, particularly for modeling and prediction
      purposes, however, suggest that other more "integrated" measures of catchment
      soil P status, such as baseflow P concentrations or streambed sediment P
      concentrations, might be more useful. Since observed soil P distribution is
      variable and is also difficult to relate to nationally available soil P data, any
      assessment of soil P status for determining risk of P loss is uncertain and
      problematic, given other catchment physicochemical characteristics and the
      sampling strategy employed.

PMID- 16275729
TI  - Transport and fate of nitrate and pesticides: hydrogeology and riparian zone
      processes.
AB  - There is continuing concern over potential impacts of widespread application of
      nutrients and pesticides on ground- and surface-water quality. Transport and fate
      of nitrate and pesticides were investigated in a shallow aquifer and adjacent
      stream, Cow Castle Creek, in Orangeburg County, South Carolina. Pesticide and
      pesticide degradate concentrations were detected in ground water with greatest
      frequency and largest concentrations directly beneath and downgradient from the
      corn (Zea mays L.) field where they were applied. In almost all samples in which
      they were detected, concentrations of pesticide degradates greatly exceeded those
      of parent compounds, and were still present in ground waters that were recharged
      during the previous 18 yr. The absence of both parent and degradate compounds in
      samples collected from deeper in the aquifer suggests that this persistence is
      limited or that the ground water had recharged before use of the pesticide.
      Concentrations of NO(-)(3) in ground water decreased with increasing depth and
      age, but denitrification was not a dominant controlling factor. Hydrologic and
      chemical data indicated that ground water discharges to the creek and chemical
      exchange takes place within the upper 0.7 m of the streambed. Ground water had
      its greatest influence on surface-water chemistry during low-flow periods,
      causing a decrease in concentrations of Cl(-), NO(-)(3), pesticides, and
      pesticide degradates. Conversely, shallow subsurface drainage dominates stream
      chemistry during high-flow periods, increasing stream concentrations of Cl(-),
      NO(-)(3), pesticides, and pesticide degradates. These results point out the
      importance of understanding the hydrogeologic setting when investigating
      transport and fate of contaminants in ground water and surface water.

PMID- 16275730
TI  - Phosphorus, sediment, and Escherichia coli loads in unfenced streams of the
      Georgia Piedmont, USA.
AB  - Contamination of unfenced streams with P, sediments, and pathogenic bacteria from
      cattle (Bos taurus) activity may be affected by the availability of shade and
      alternative water sources. The objectives of this study were to evaluate water
      quality in two streams draining tall fescue (Festuca arundinacea Schreb.)-common
      bermudagrass (Cynodon dactylon L.) pastures with different shade distribution,
      and to quantify the effects of alternative water sources on stream water quality.
      For 3 yr, loads of dissolved reactive phosphorus (DRP), total phosphorus (TP),
      and total suspended solids (TSS) were measured during storm flow, and loads of
      DRP, TP, TSS, and Escherichia coli were measured every 14 d during base flow. We
      also used GPS collars to determine amount of time cattle spent in riparian areas.
      Our results showed that cattle-grazed pastures with unfenced streams contributed
      significant loads of DRP, TP, TSS, and E. coli to surface waters (p < 0.01). Time
      spent by cattle in riparian areas as well as storm flow loads of DRP, TP, and TSS
      were larger (p < 0.08) in the pasture with the smaller amount of nonriparian
      shade. Water trough availability decreased base flow loads of TSS and E. coli in
      both streams, and decreased time cattle spent in riparian areas in the pasture
      with the smaller amount of nonriparian shade (p < 0.08). Our results indicate
      that possible BMPs to reduce contamination from cattle-grazed pastures would be
      to develop or encourage nonriparian shade and to provide cattle with alternative
      water sources away from the stream.

PMID- 16275731
TI  - Freeze-thaw effects on phosphorus loss in runoff from manured and catch-cropped
      soils.
AB  - Concern over nonpoint source P losses from agricultural lands to surface waters
      in frigid climates has focused attention on the role of freezing and thawing on P
      loss from catch crops (cover crops). This study evaluated the effect of freezing
      and thawing on the fate of P in bare soils, soils mixed with dairy manure, and
      soils with an established catch crop of annual ryegrass (Lolium multiflorum L.).
      Experiments were conducted to evaluate changes in P runoff from packed soil boxes
      (100 by 20 by 5 cm) and P leaching from intact soil columns (30 cm deep). Before
      freezing and thawing, total P (TP) in runoff from catch-cropped soils was lower
      than from manured and bare soils due to lower erosion. Repeated freezing and
      thawing significantly increased water-extractable P (WEP) from catch crop biomass
      and resulted in significantly elevated concentrations of dissolved P in runoff
      (9.7 mg L(-1)) compared with manured (0.18 mg L(-1)) and bare soils (0.14 mg L(
      1)). Catch crop WEP was strongly correlated with the number of freeze-thaw
      cycles. Freezing and thawing did not change the WEP of soils mixed with manures,
      nor were differences observed in subsurface losses of P between catch-cropped and
      bare soils before or after manure application. This study illustrates the trade
      offs of establishing catch crops in frigid climates, which can enhance P uptake
      by biomass and reduce erosion potential but increase dissolved P runoff.

PMID- 16275732
TI  - Assessment of wool waste and hair waste as soil amendment and nutrient source.
AB  - A field and two container experiments were conducted to assess uncomposted wool
      and hair wastes as a nutrient source for crops and to evaluate their potential to
      improve soil biological and chemical properties. Overall, addition of wool or
      hair waste to soil increased yields of basil (Ocimum basilicum L. 'Trakia'),
      thorn apple (Datura innoxia Mill. 'Inka'), peppermint (Mentha x piperita L.
      'Black Mitchum'), and garden sage (Salvia officinalis L. 'Desislava'), increased
      NH(4)-N and NO(3)-N in soil, increased total N (and protein) content in plant
      tissue, stimulated soil microbial biomass, and decreased mycorrhizae colonization
      of plant roots of thorn apple but not in basil. Wool and hair waste additions to
      soil altered slightly the content and composition of plant secondary metabolites
      (essential oils or alkaloids); however, overall the constituents remained within
      the "typical" range for the respective crops. Scanning electron microscopy (SEM)
      and energy dispersive X-ray (EDX) analysis demonstrated that wool and hair wastes
      decompose slowly under field or greenhouse conditions, and act as a slow release
      S, N, P, and K fertilizer. These results, along with the measured concentrations
      of NO(3)-N in soil at harvest, suggest that the addition of wool or hair waste of
      only 3.3 g kg(-1) of soil may support two to five harvests or crops under
      greenhouse conditions and two to four field seasons in field production systems,
      and would improve soil biological and chemical characteristics. Further research
      is needed to optimize the rate of application of these waste materials to the
      nutrient requirements of specific crops to avoid nitrate leaching into the ground
      water. In addition, the effect of wool and hair waste on other environmental end
      points should also be further investigated before specific recommendations for
      growers are provided.

PMID- 16275733
TI  - Chemical and physical changes following co-composting of beef cattle feedlot
      manure with phosphogypsum.
AB  - Nitrogen (N) loss during beef cattle (Bos taurus) feedlot manure composting may
      contribute to greenhouse gas emissions and increase ammonia (NH(3)) in the
      atmosphere while decreasing the fertilizer value of the final compost.
      Phosphogypsum (PG) is an acidic by-product of phosphorus (P) fertilizer
      manufacture and large stockpiles currently exist in Alberta. This experiment
      examined co-composting of PG (at rates of 0, 40, 70, and 140 kg PG Mg(-1) manure
      plus PG dry weight) with manure from feedlot pens bedded with straw or wood
      chips. During the 99-d composting period, PG addition reduced total nitrogen (TN)
      loss by 0.11% for each 1 kg Mg(-1) increment in PG rate. Available N at the end
      of composting was significantly higher for wood chip-bedded (2180 mg kg(-1)) than
      straw-bedded manure treatments (1820 mg kg(-1)). Total sulfur (TS) concentration
      in the final compost increased by 0.19 g kg(-1) for each 1 kg Mg(-1) increment in
      PG rate from 5.2 g TS kg(-1) without PG addition. Phosphogypsum (1.6 g kg(-1) P)
      addition had no significant effect on total phosphorus (TP) concentration of the
      final composts. Results from this study demonstrate the potential of PG addition
      to reduce overall N losses during composting. The accompanying increase in TS
      content has implications for use of the end-product on sulfur-deficient soils. Co
      composting feedlot manure with PG may provide an inexpensive and technologically
      straightforward solution for managing and improving the nutrient composition of
      composted cattle manure.

PMID- 16275734
TI  - HPLC-MSn to investigate the oxidative destruction pathway of aromatic sulfonate
      wastes.
AB  - The article concerns the problem of destruction and remediation of industrial
      wastes containing aromatic sulfonates. The effects of an oxidation process
      induced by thermally activated persulfate in the degradation of 1,5
      naphthalenedisulfonate (NDS) are investigated by the use of UV-Vis
      spectrophotometry, high performance liquid chromatography-mass spectrometry (HPLC
      MS) and HPLC-MS(n) techniques. The results obtained indicated that thermal
      activation (80 degrees C) of a solution containing NDS and sodium persulfate in a
      molar ratio equal to 1 leads to the cleavage of the naphthalene structure.
      Estimated chemical oxygen demand (COD) indicates that when the excess of
      persulfate is equal to 100, NDS undergoes a mineralization of the order of 90%. A
      degradation pathway undergone by NDS when thermally activated in the presence of
      persulfate is proposed.

PMID- 16275735
TI  - The stem cell shell game. Focus on "The postnatal rat aorta contains pericyte
      progenitor cells that form spheroidal colonies in suspension culture".

PMID- 16275736
TI  - Myosin filament assembly in an ever-changing myofilament lattice of smooth
      muscle.
AB  - A major development in smooth muscle research in recent years is the recognition
      that the myofilament lattice of the muscle is malleable. The malleability appears
      to stem from plastic rearrangement of contractile and cytoskeletal filaments in
      response to stress and strain exerted on the muscle cell, and it allows the
      muscle to adapt to a wide range of cell lengths and maintain optimal
      contractility. Although much is still poorly understood, we have begun to
      comprehend some of the basic mechanisms underlying the assembly and disassembly
      of contractile and cytoskeletal filaments in smooth muscle during the process of
      adaptation to large changes in cell geometry. One factor that likely facilitates
      the plastic length adaptation is the ability of myosin filaments to form and
      dissolve at the right place and the right time within the myofilament lattice. It
      is proposed herein that formation of myosin filaments in vivo is aided by the
      various filament-stabilizing proteins, such as caldesmon, and that the thick
      filament length is determined by the dimension of the actin filament lattice. It
      is still an open question as to how the dimension of the dynamic filament lattice
      is regulated. In light of the new perspective of malleable myofilament lattice in
      smooth muscle, the roles of many smooth muscle proteins could be assigned or
      reassigned in the context of plastic reorganization of the contractile apparatus
      and cytoskeleton.

PMID- 16275737
TI  - CBS domains: structure, function, and pathology in human proteins.
AB  - The cystathionine-beta-synthase (CBS) domain is an evolutionarily conserved
      protein domain that is present in the proteome of archaebacteria, prokaryotes,
      and eukaryotes. CBS domains usually come in tandem repeats and are found in
      cytosolic and membrane proteins performing different functions (metabolic
      enzymes, kinases, and channels). Crystallographic studies of bacterial CBS
      domains have shown that two CBS domains form an intramolecular dimeric structure
      (CBS pair). Several human hereditary diseases (homocystinuria, retinitis
      pigmentosa, hypertrophic cardiomyopathy, myotonia congenital, etc.) can be caused
      by mutations in CBS domains of, respectively, cystathionine-beta-synthase,
      inosine 5'-monophosphate dehydrogenase, AMP kinase, and chloride channels.
      Despite their clinical relevance, it remains to be established what the precise
      function of CBS domains is and how they affect the structural and/or functional
      properties of an enzyme, kinase, or channel. Depending on the protein in which
      they occur, CBS domains have been proposed to affect multimerization and sorting
      of proteins, channel gating, and ligand binding. However, recent experiments
      revealing that CBS domains can bind adenosine-containing ligands such ATP, AMP,
      or S-adenosylmethionine have led to the hypothesis that CBS domains function as
      sensors of intracellular metabolites.

PMID- 16275738
TI  - Are biogenic amines involved in controlling upper airway patency during REM
      sleep?

PMID- 16275739
TI  - Black Hawk, please come down: reflections on a hospital's struggle to survive in
      the wake of Hurricane Katrina.

PMID- 16275740
TI  - Risk factors for tuberculosis among HIV-infected patients receiving
      antiretroviral treatment.

PMID- 16275741
TI  - The brush cell.

PMID- 16275742
TI  - Effect of CPAP and lung volume on obstructive sleep apnea.

PMID- 16275743
TI  - An incredible decade for the primary cilium: a look at a once-forgotten
      organelle.
AB  - Since the discovery that numerous proteins involved in mammalian disease localize
      to the basal bodies and cilia, these organelles have emerged from relative
      obscurity to the center of intense research efforts in an expanding number of
      disease- and developmental-related fields. Our understanding of the association
      between cilia and human disease has benefited substantially from the use of lower
      organisms such as Chlamydomonas and Caenorhabditis elegans and the availability
      of murine models and cell culture. These research endeavors led to the discovery
      that loss of normal ciliary function in mammals is responsible for cystic and
      noncystic pathology in the kidney, liver, brain, and pancreas, as well as severe
      developmental patterning abnormalities. In addition, the localization of proteins
      involved in rare human disorders such as Bardet-Biedl syndrome has suggested that
      cilia-related dysfunction may play a role in modern human epidemics such as
      hypertension, obesity, and diabetes. Although we have made great advances in
      demonstrating the importance of cilia over the past decade, the physiological
      role that this organelle plays in most tissues remains elusive. Research focused
      on addressing this issue will be of critical importance for a further
      understanding of how ciliary dysfunction can lead to such severe disease and
      developmental pathologies.

PMID- 16275745
TI  - Alternative renin regulatory pathways and the NKCC1 isoform.

PMID- 16275744
TI  - "Phosphatonins" and the regulation of phosphorus homeostasis.
AB  - Phosphate ions are critical for normal bone mineralization, and phosphate plays a
      vital role in a number of other biological processes such as signal transduction,
      nucleotide metabolism, and enzyme regulation. The study of rare disorders
      associated with renal phosphate wasting has resulted in the discovery of a number
      of proteins [fibroblast growth factor 23 (FGF-23), secreted frizzled related
      protein 4 (sFRP-4), matrix extracellular phosphoglycoprotein, and FGF 7 (FGF-7)]
      that decrease renal sodium-dependent phosphate transport in vivo and in vitro.
      The "phosphatonins," FGF-23 and sFRP-4, also inhibit the synthesis of 1alpha,25
      dihydroxyvitamin D, leading to decreased intestinal phosphate absorption and
      further reduction in phosphate retention by the organism. In this review, we
      discuss the biological properties of these proteins, alterations in their
      concentrations in various clinical disorders, and their possible physiological
      role.

PMID- 16275746
TI  - Proximal tubule water transport-lessons from aquaporin knockout mice.

PMID- 16275748
TI  - Spying on IgE receptor signaling: simply complex, or not?
AB  - Plasma membrane organization and the potential role, or not, of lipid raft
      microdomains in signal transduction is a controversial topic. Cross-correlation
      fluorescent correlation spectroscopy (CC-FCS) shows promise as a new approach to
      rapidly probe protein-protein interactions in living cells during signal
      transduction. CC-FCS data from studies of IgE receptor signaling challenge models
      of large stable lipid raft signaling domains and reveal a new complexity in the
      dynamic (re)organization of signaling complexes.

PMID- 16275749
TI  - Complete maturation of the plastid protein translocation channel requires a type
      I signal peptidase.
AB  - The protein translocation channel at the plastid outer envelope membrane, Toc75,
      is essential for the viability of plants from the embryonic stage. It is encoded
      in the nucleus and is synthesized with a bipartite transit peptide that is
      cleaved during maturation. Despite its important function, the molecular
      mechanism and the biological significance of the full maturation of Toc75 remain
      unclear. In this study, we show that a type I signal peptidase (SPase I) is
      responsible for this process. First, we demonstrate that a bacterial SPase I
      converted Toc75 precursor to its mature form in vitro. Next, we show that
      disruption of a gene encoding plastidic SPase I (Plsp1) resulted in the
      accumulation of immature forms of Toc75, severe reduction of plastid internal
      membrane development, and a seedling lethal phenotype. These phenotypes were
      rescued by the overexpression of Plsp1 complementary DNA. Plsp1 appeared to be
      targeted both to the envelope and to the thylakoidal membranes; thus, it may have
      multiple functions.

PMID- 16275750
TI  - Centrobin: a novel daughter centriole-associated protein that is required for
      centriole duplication.
AB  - In mammalian cells, the centrosome consists of a pair of centrioles and amorphous
      pericentriolar material. The pair of centrioles, which are the core components of
      the centrosome, duplicate once per cell cycle. Centrosomes play a pivotal role in
      orchestrating the formation of the bipolar spindle during mitosis. Recent studies
      have linked centrosomal activity on centrioles or centriole-associated structures
      to cytokinesis and cell cycle progression through G1 into the S phase. In this
      study, we have identified centrobin as a centriole-associated protein that
      asymmetrically localizes to the daughter centriole. The silencing of centrobin
      expression by small interfering RNA inhibited centriole duplication and resulted
      in centrosomes with one or no centriole, demonstrating that centrobin is required
      for centriole duplication. Furthermore, inhibition of centriole duplication by
      centrobin depletion led to impaired cytokinesis.

PMID- 16275751
TI  - MyoD induces myogenic differentiation through cooperation of its NH2- and COOH
      terminal regions.
AB  - MyoD and Myf5 are basic helix-loop-helix transcription factors that play key but
      redundant roles in specifying myogenic progenitors during embryogenesis. However,
      there are functional differences between the two transcription factors that
      impact myoblast proliferation and differentiation. Target gene activation could
      be one such difference. We have used microarray and polymerase chain reaction
      approaches to measure the induction of muscle gene expression by MyoD and Myf5 in
      an in vitro model. In proliferating cells, MyoD and Myf5 function very similarly
      to activate the expression of likely growth phase target genes such as L-myc, m
      cadherin, Mcpt8, Runx1, Spp1, Six1, IGFBP5, and Chrnbeta1. MyoD, however, is
      strikingly more effective than Myf5 at inducing differentiation-phase target
      genes. This distinction between MyoD and Myf5 results from a novel and
      unanticipated cooperation between the MyoD NH2- and COOH-terminal regions.
      Together, these results support the notion that Myf5 functions toward myoblast
      proliferation, whereas MyoD prepares myoblasts for efficient differentiation.

PMID- 16275752
TI  - IGF-I increases bone marrow contribution to adult skeletal muscle and enhances
      the fusion of myelomonocytic precursors.
AB  - Muscle damage has been shown to enhance the contribution of bone marrow-derived
      cells (BMDCs) to regenerating skeletal muscle. One responsible cell type involved
      in this process is a hematopoietic stem cell derivative, the myelomonocytic
      precursor (MMC). However, the molecular components responsible for this injury
      related response remain largely unknown. In this paper, we show that delivery of
      insulin-like growth factor I (IGF-I) to adult skeletal muscle by three different
      methods-plasmid electroporation, injection of genetically engineered myoblasts,
      and recombinant protein injection-increases the integration of BMDCs up to
      fourfold. To investigate the underlying mechanism, we developed an in vitro
      fusion assay in which co-cultures of MMCs and myotubes were exposed to IGF-I. The
      number of fusion events was substantially augmented by IGF-I, independent of its
      effect on cell survival. These results provide novel evidence that a single
      factor, IGF-I, is sufficient to enhance the fusion of bone marrow derivatives
      with adult skeletal muscle.

PMID- 16275753
TI  - A primate virus generates transformed human cells by fusion.
AB  - Amodel that explains both the origin and sporadic nature of cancer argues that
      cancer cells are a chance result of events that cause genomic and epigenetic
      variability. The prevailing view is that these events are mutations that affect
      chromosome segregation or stability. However, genomic and epigenetic variability
      is also triggered by cell fusion, which is often caused by viruses. Yet, cells
      fused by viruses are considered harmless because they die. We provide evidence
      that a primate virus uses both viral and exosomal proteins involved in cell
      fusion to produce transformed proliferating human cells. Although normal cells
      indeed fail to proliferate after fusion, expression of an oncogene or a mutated
      tumor suppressor p53 in just one of the fusion partners is sufficient to produce
      heterogeneous progeny. We also show that this virus can produce viable
      oncogenically transformed cells by fusing cells that are otherwise destined to
      die. Therefore, we argue that viruses can contribute to carcinogenesis by fusing
      cells.

PMID- 16275754
TI  - FAK signaling is critical for ErbB-2/ErbB-3 receptor cooperation for oncogenic
      transformation and invasion.
AB  - The overexpression of members of the ErbB tyrosine kinase receptor family has
      been associated with cancer progression. We demonstrate that focal adhesion
      kinase (FAK) is essential for oncogenic transformation and cell invasion that is
      induced by ErbB-2 and -3 receptor signaling. ErbB-2/3 overexpression in FAK
      deficient cells fails to promote cell transformation and rescue chemotaxis
      deficiency. Restoration of FAK rescues both oncogenic transformation and invasion
      that is induced by ErbB-2/3 in vitro and in vivo. In contrast, the inhibition of
      FAK in FAK-proficient invasive cancer cells prevented cell invasion and
      metastasis formation. The activation of ErbB-2/3 regulates FAK phosphorylation at
      Tyr-397, -861, and -925. ErbB-induced oncogenic transformation correlates with
      the ability of FAK to restore ErbB-2/3-induced mitogen-activated protein kinase
      (MAPK) activation; the inhibition of MAPK prevented oncogenic transformation. In
      contrast, the inhibition of Src but not MAPK prevented ErbB-FAK-induced
      chemotaxis. In migratory cells, activated ErbB-2/3 receptors colocalize with
      activated FAK at cell protrusions. This colocalization requires intact FAK. In
      summary, distinct FAK signaling has an essential function in ErbB-induced
      oncogenesis and invasiveness.

PMID- 16275755
TI  - Temporally resolved interactions between antigen-stimulated IgE receptors and Lyn
      kinase on living cells.
AB  - Upon cross-linking by antigen, the high affinity receptor for immunoglobulin E
      (IgE), FcepsilonRI, is phosphorylated by the Src family tyrosine kinase Lyn to
      initiate mast cell signaling, leading to degranulation. Using fluorescence
      correlation spectroscopy (FCS), we observe stimulation-dependent associations
      between fluorescently labeled IgE-FcepsilonRI and Lyn-EGFP on individual cells.
      We also simultaneously measure temporal variations in the lateral diffusion of
      these proteins. Antigen-stimulated interactions between these proteins detected
      subsequent to the initiation of receptor phosphorylation exhibit time-dependent
      changes, suggesting multiple associations between FcepsilonRI and Lyn-EGFP.
      During this period, we also observe a persistent decrease in Lyn-EGFP lateral
      diffusion that is dependent on Src family kinase activity. These stimulated
      interactions are not observed between FcepsilonRI and a chimeric EGFP that
      contains only the membrane-targeting sequence from Lyn. Our results reveal real
      time interactions between Lyn and cross-linked FcepsilonRI implicated in
      downstream signaling events. They demonstrate the capacity of FCS cross
      correlation analysis to investigate the mechanism of signaling-dependent protein
      protein interactions in intact, living cells.

PMID- 16275756
TI  - CaMKII tethers to L-type Ca2+ channels, establishing a local and dedicated
      integrator of Ca2+ signals for facilitation.
AB  - Ca2+-dependent facilitation (CDF) of voltage-gated calcium current is a powerful
      mechanism for up-regulation of Ca2+ influx during repeated membrane
      depolarization. CDF of L-type Ca2+ channels (Ca(v)1.2) contributes to the
      positive force-frequency effect in the heart and is believed to involve the
      activation of Ca2+/calmodulin-dependent kinase II (CaMKII). How CaMKII is
      activated and what its substrates are have not yet been determined. We show that
      the pore-forming subunit alpha(1C) (Ca(v)alpha1.2) is a CaMKII substrate and that
      CaMKII interaction with the COOH terminus of alpha1C is essential for CDF of L
      type channels. Ca2+ influx triggers distinct features of CaMKII targeting and
      activity. After Ca2+-induced targeting to alpha1C, CaMKII becomes tightly
      tethered to the channel, even after calcium returns to normal levels. In
      contrast, activity of the tethered CaMKII remains fully Ca2+/CaM dependent,
      explaining its ability to operate as a calcium spike frequency detector. These
      findings clarify the molecular basis of CDF and demonstrate a novel enzymatic
      mechanism by which ion channel gating can be modulated by activity.

PMID- 16275758
TI  - Lost in translation: barriers to implementing clinical immunotherapeutics for
      autoimmunity.
AB  - Induction of selective, autoantigen-specific tolerance is the "holy grail" for
      the treatment and prevention of autoimmune diseases. Despite successes in many
      differential murine models, rational and efficient translation to the clinic has
      been difficult. During the 5th Annual Federation of Clinical Immunological
      Societies (FOCIS) Meeting, May 12-16, 2005, in Boston, MA, a Kirin-sponsored
      "Ideashop" was convened to discuss this theme amongst scientists, clinicians,
      industry partners, and funding agencies.

PMID- 16275757
TI  - The matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts.
AB  - Integrin-mediated cell adhesion to extracellular matrix proteins is known to
      promote cell survival, whereas detachment from the matrix can cause rapid
      apoptotic death in some cell types. Contrary to this paradigm, we show that
      fibroblast adhesion to the angiogenic matrix protein CCN1 (CYR61) induces
      apoptosis, whereas endothelial cell adhesion to CCN1 promotes cell survival. CCN1
      induces fibroblast apoptosis through its adhesion receptors, integrin alpha6beta1
      and the heparan sulfate proteoglycan (HSPG) syndecan-4, triggering the
      transcription-independent p53 activation of Bax to render cytochrome c release
      and activation of caspase-9 and -3. Neither caspase-8 activity nor de novo
      transcription or translation is required for this process. These results show
      that cellular interaction with a specific matrix protein can either induce or
      suppress apoptosis in a cell type-specific manner and that integrin alpha6beta1
      HSPGs can function as receptors to induce p53-dependent apoptosis.

PMID- 16275759
TI  - Suppression of allergic airway inflammation by helminth-induced regulatory T
      cells.
AB  - Allergic diseases mediated by T helper type (Th) 2 cell immune responses are
      rising dramatically in most developed countries. Exaggerated Th2 cell reactivity
      could result, for example, from diminished exposure to Th1 cell-inducing
      microbial infections. Epidemiological studies, however, indicate that Th2 cell
      stimulating helminth parasites may also counteract allergies, possibly by
      generating regulatory T cells which suppress both Th1 and Th2 arms of immunity.
      We therefore tested the ability of the Th2 cell-inducing gastrointestinal
      nematode Heligmosomoides polygyrus to influence experimentally induced airway
      allergy to ovalbumin and the house dust mite allergen Der p 1. Inflammatory cell
      infiltrates in the lung were suppressed in infected mice compared with uninfected
      controls. Suppression was reversed in mice treated with antibodies to CD25. Most
      notably, suppression was transferable with mesenteric lymph node cells (MLNC)
      from infected animals to uninfected sensitized mice, demonstrating that the
      effector phase was targeted. MLNC from infected animals contained elevated
      numbers of CD4(+)CD25(+)Foxp3(+) T cells, higher TGF-beta expression, and
      produced strong interleukin (IL)-10 responses to parasite antigen. However, MLNC
      from IL-10-deficient animals transferred suppression to sensitized hosts,
      indicating that IL-10 is not the primary modulator of the allergic response.
      Suppression was associated with CD4(+) T cells from MLNC, with the CD4(+)CD25(+)
      marker defining the most active population. These data support the contention
      that helminth infections elicit a regulatory T cell population able to down
      regulate allergen induced lung pathology in vivo.

PMID- 16275760
TI  - TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell
      response through OX40 ligand.
AB  - We recently showed that dendritic cells (DCs) activated by thymic stromal
      lymphopoietin (TSLP) prime naive CD4(+) T cells to differentiate into T helper
      type 2 (Th2) cells that produced high amounts of tumor necrosis factor-alpha (TNF
      alpha), but no interleukin (IL)-10. Here we report that TSLP induced human DCs to
      express OX40 ligand (OX40L) but not IL-12. TSLP-induced OX40L on DCs was required
      for triggering naive CD4(+) T cells to produce IL-4, -5, and -13. We further
      revealed the following three novel functional properties of OX40L: (a) OX40L
      selectively promoted TNF-alpha, but inhibited IL-10 production in developing Th2
      cells; (b) OX40L lost the ability to polarize Th2 cells in the presence of IL-12;
      and (c) OX40L exacerbated IL-12-induced Th1 cell inflammation by promoting TNF
      alpha, while inhibiting IL-10. We conclude that OX40L on TSLP-activated DCs
      triggers Th2 cell polarization in the absence of IL-12, and propose that OX40L
      can switch IL-10-producing regulatory Th cell responses into TNF-alpha-producing
      inflammatory Th cell responses.

PMID- 16275761
TI  - Interaction of CagA with Crk plays an important role in Helicobacter pylori
      induced loss of gastric epithelial cell adhesion.
AB  - CagA protein is a major virulence factor of Helicobacter pylori, which is
      delivered into gastric epithelial cells and elicits growth factor-like responses.
      Once within the cells, CagA is tyrosine phosphorylated by Src family kinases and
      targets host proteins required to induce the cell responses. We show that the
      phosphorylated CagA binds Crk adaptor proteins (Crk-II, Crk-I, and Crk-L) and
      that the interaction is important for the CagA-mediated host responses during H.
      pylori infection. H. pylori-induced scattering of gastric epithelial cells in
      culture was blocked by overexpression of dominant-negative Crk and by RNA
      interference-mediated knockdown of endogenous Crk. H. pylori infection of the
      gastric epithelium induced disruption of E-cadherin/catenin-containing adherens
      junctions, which was also dependent on CagA/Crk signaling. Furthermore,
      inhibition of the SoS1/H-Ras/Raf1, C3G/Rap1/B-Raf, or Dock180/Rac1/Wiskott
      Aldrich syndrome protein family verprolin homologous protein pathway, all of
      which are involved downstream of Crk adaptors, greatly diminished the CagA
      associated host responses. Thus, CagA targeting of Crk plays a central role in
      inducing the pleiotropic cell responses to H. pylori infection that cause several
      gastric diseases, including gastric cancer.

PMID- 16275762
TI  - The immunogenicity of a viral cytotoxic T cell epitope is controlled by its MHC
      bound conformation.
AB  - Thousands of potentially antigenic peptides are encoded by an infecting pathogen;
      however, only a small proportion induce measurable CD8(+) T cell responses. To
      investigate the factors that control peptide immunogenicity, we have examined the
      cytotoxic T lymphocyte (CTL) response to a previously undefined epitope
      ((77)APQPAPENAY(86)) from the BZLF1 protein of Epstein-Barr virus (EBV). This
      peptide binds well to two human histocompatibility leukocyte antigen (HLA)
      allotypes, HLA-B*3501 and HLA-B*3508, which differ by a single amino acid at
      position 156 ((156)Leucine vs. (156)Arginine, respectively). Surprisingly, only
      individuals expressing HLA-B*3508 show evidence of a CTL response to the
      (77)APQPAPENAY(86) epitope even though EBV-infected cells expressing HLA-B*3501
      process and present similar amounts of peptide for CTL recognition, suggesting
      that factors other than peptide presentation levels are influencing
      immunogenicity. Functional and structural analysis revealed marked conformational
      differences in the peptide, when bound to each HLA-B35 allotype, that are
      dictated by the polymorphic HLA residue 156 and that directly affected T cell
      receptor recognition. These data indicate that the immunogenicity of an antigenic
      peptide is influenced not only by how well the peptide binds to major
      histocompatibility complex (MHC) molecules but also by its bound conformation. It
      also illustrates a novel mechanism through which MHC polymorphism can further
      diversify the immune response to infecting pathogens.

PMID- 16275764
TI  - CD4 T cells integrate signals delivered during successive DC encounters in vivo.
AB  - The cellular mode of T cell priming in vivo remains to be characterized fully. We
      investigated the fate of T cell-dendritic cell (DC) interactions in the late
      phase of T cell activation in the lymph node. In general, CD4 T cells detach from
      DCs before undergoing cell division. Using a new approach to track the history of
      antigen (Ag)-recognition events, we demonstrated that activated/divided T cells
      reengage different DCs in an Ag-specific manner. Two-photon imaging of intact
      lymph nodes suggested that T cells could establish prolonged interactions with
      DCs at multiple stages during the activation process. Importantly, signals that
      are delivered during subsequent DC contacts are integrated by the T cell and
      promote sustained IL-2Ralpha expression and IFN-gamma production. Thus, repeated
      encounters with Ag-bearing DCs can occur in vivo and modulate CD4 T cell
      differentiation programs.

PMID- 16275763
TI  - Autoamplification of NFATc1 expression determines its essential role in bone
      homeostasis.
AB  - NFATc1 and NFATc2 are functionally redundant in the immune system, but it was
      suggested that NFATc1 is required exclusively for differentiation of osteoclasts
      in the skeletal system. Here we provide genetic evidence that NFATc1 is essential
      for osteoclast differentiation in vivo by adoptive transfer of NFATc1(-/-)
      hematopoietic stem cells to osteoclast-deficient Fos(-/-) mice, and by Fos(-/-)
      blastocyst complementation, thus avoiding the embryonic lethality of NFATc1(-/-)
      mice. However, in vitro osteoclastogenesis in NFATc1-deficient cells was rescued
      by ectopic expression of NFATc2. The discrepancy between the in vivo essential
      role of NFATc1 and the in vitro effect of NFATc2 was attributed to selective
      autoregulation of the NFATc1 gene by NFAT through its promoter region. This
      suggested that an epigenetic mechanism contributes to the essential function of
      NFATc1 in cell lineage commitment. Thus, this study establishes that NFATc1
      represents a potential therapeutic target for bone disease and reveals a
      mechanism that underlies the essential role of NFATc1 in bone homeostasis.

PMID- 16275765
TI  - Differential antitumor immunity mediated by NKT cell subsets in vivo.
AB  - We showed previously that NKT cell-deficient TCR Jalpha18(-/-) mice are more
      susceptible to methylcholanthrene (MCA)-induced sarcomas, and that normal tumor
      surveillance can be restored by adoptive transfer of WT liver-derived NKT cells.
      Liver-derived NKT cells were used in these studies because of their relative
      abundance in this organ, and it was assumed that they were representative of NKT
      cells from other sites. We compared NKT cells from liver, thymus, and spleen for
      their ability to mediate rejection of the sarcoma cell line (MCA-1) in vivo, and
      found that this was a specialized function of liver-derived NKT cells.
      Furthermore, when CD4(+) and CD4(-) liver-derived NKT cells were administered
      separately, MCA-1 rejection was mediated primarily by the CD4(-) fraction. Very
      similar results were achieved using the B16F10 melanoma metastasis model, which
      requires NKT cell stimulation with alpha-galactosylceramide. The impaired ability
      of thymus-derived NKT cells was due, in part, to their production of IL-4,
      because tumor immunity was clearly enhanced after transfer of IL-4-deficient
      thymus-derived NKT cells. This is the first study to demonstrate the existence of
      functionally distinct NKT cell subsets in vivo and may shed light on the long
      appreciated paradox that NKT cells function as immunosuppressive cells in some
      disease models, whereas they promote cell-mediated immunity in others.

PMID- 16275767
TI  - Circadian rhythm of a TCA cycle enzyme is apparently regulated at the
      translational level in the dinoflagellate Lingulodinium polyedrum.
AB  - Previously, the authors have reported that intracellular amounts of several
      metabolic-related enzymes from the photosynthetic dinoflagellate Lingulodinium
      polyedrum(formerly Gonyaulax polyedra) showed a daily rhythm under a 12:12 h LD
      cycle. This led the authors to hypothesize that a circadian clock controls
      metabolism, including the tricarboxylic acid (TCA) cycle. In this study, the
      authors investigated daily changes in the levels of mRNA, protein, and enzyme
      activity of several metabolic enzymes during 12:12 h LD, 8:16 h LD, and constant
      light conditions. The NADP-dependent isocitrate dehydrogenase (NADPICDH) in the
      TCA cycle exhibited circadian changes of protein abundance and enzyme activity
      under all conditions, whereas its mRNA level remained constant throughout the
      cycle. These results indicate that the rhythm of NADPICDH is regulated by a
      circadian control of protein synthesis or modification rather than by message
      levels and suggest that the TCA cycle may be controlled by the circadian clock
      system.

PMID- 16275766
TI  - IL-2 production in developing Th1 cells is regulated by heterodimerization of
      RelA and T-bet and requires T-bet serine residue 508.
AB  - Interleukin (IL)-2 is the predominant cytokine that is produced by naive Th cells
      in a primary response. It is required for proliferation and differentiation of Th
      precursor cells into effector cells. Initial high-level IL-2 production is
      followed by its decline, and the concomitant induction of cytokines that are
      typical of the differentiated state. Although the factors that are responsible
      for the early induction of IL-2 are well defined, the mechanisms that are
      responsible for its down-regulation in later stages of Th development have not
      been studied as much. Previous work from our laboratory revealed a repressor
      function for the T-box transcription factor, T-bet, in IL-2 gene transcription.
      Here, we report that T-bet(S508) is required for the optimal repression of IL-2
      production in developing Th1 cells. Phosphorylation of T-bet(S508) by casein
      kinase I and glycogen synthase kinase-3 kinases accompanies T-bet's interaction
      with the RelA nuclear factor-kappaB transcription factor. Heterodimerization of T
      bet and RelA interferes with the binding of RelA to the IL-2 promoter, and hence,
      transcriptional activation of the IL-2 gene by RelA.

PMID- 16275768
TI  - Evolution of a length polymorphism in the human PER3 gene, a component of the
      circadian system.
AB  - Period homologue 3 (PER3) is a component of the mammalian circa-dian system,
      although its precise role is unknown. A biallelic variable number tandem repeat
      (VNTR) polymorphism exists in human PER3, consisting of 4 or 5 repeats of a 54-bp
      sequence in a region encoding a putative phosphorylation domain. This
      polymorphism has previously been reported to associate with diurnal preference
      ("morningness" and "eveningness") and delayed sleep-phase syndrome. We have
      investigated the global allele frequencies of this variant in ethnically distinct
      indigenous populations. All populations were polymorphic, with the shorter (4
      repeat) allele ranging in frequency from 0.19 (Papua New Guinea) to 0.89
      (Mongolia). To investigate if allele frequency has been influenced by natural
      selection, the authors 1) tested for a correlation with latitude and mean annual
      insolation (incident sunlight energy), using classical markers to correct for
      historical population differentiation; and they 2) compared allele-frequency
      difference between European American, African American, and East Asian
      populations, as measured using F(ST), to an empirical null distribution of
      F(ST)values based on a genome-wide dataset of single nucleotide polymorphisms
      (SNPs) of presumed neutral loci that were previously typed by The SNP Consortium.
      The variation in allele frequencies between indigenous populations did not show a
      pattern that would indicate selective pressure on PER3resulting from day-length
      variation or mean annual insolation, and the allele-frequency difference between
      European Americans, African Americans, and East Asians was not an outlier when
      compared to the distribution for presumed neutral SNPs. We therefore find no
      evidence for differential or balancing selection in the contemporary pattern of
      global PER3allele frequencies.

PMID- 16275770
TI  - Binocular contributions to the responsiveness and integrative capacity of the
      circadian rhythm system to light.
AB  - The retinohypothalamic tract (RHT), a monosynaptic retinal projection to the SCN,
      is the major path by which light entrains the circadian system to the external
      photoperiod. The circadian system of rodents effectively integrates or counts
      photons, and the magnitude of the rhythm phase response is proportional to the
      total energy of the photic stimulus. In the present studies, responsiveness to
      light and integrative capacity of the circadian system were tested in hamsters
      after reduction of retinal photoreceptor input by 50%. At CT 19, animals in
      constant darkness with or without unilateral retinal occlusion were exposed to 1
      of 6 irradiances of 5-min white-light pulses ranging from 0.0011 to 70
      microW/cm(2) or 5 white-light pulses of 0.6 microW/cm(2) with durations ranging
      from 0.25 to 150.0 min. Assessment of light-induced circadian rhythm phase
      response and Fos expression in the SCN by these animals revealed that a 50%
      reduction in input from photoreceptors stimulated directly with light caused a
      decrease in responsiveness to the longest duration and highest irradiance pulses
      presented. Despite this effect, both the magnitude of Fos induction in the SCN
      and phase-shift response remained directly proportional to the total energy in
      the photic stimuli. The results support the view that a reciprocal relationship
      between stimulus irradiance and duration persists despite the 50% reduction in
      retinal photoreceptor input. The mechanism of integration neither resides in the
      retina nor in the RHT.

PMID- 16275769
TI  - Effects of preparation time on phase of cultured tissues reveal complexity of
      circadian organization.
AB  - The phases of central (SCN) and peripheral circadian oscillators are held in
      specific relationships under LD cycles but, in the absence of external rhythmic
      input, may damp or drift out of phase with each other. Rats exposed to prolonged
      constant light become behaviorally arrhythmic, perhaps as a consequence of
      dissociation of phases among SCN cells. The authors asked whether individual
      central and peripheral circadian oscillators were rhythmic in LL-treated
      arrhythmic rats and, if rhythmic, what were the phase relationships between them.
      The authors prepared SCN, pineal gland, pituitary, and cornea cultures from
      transgenic Period1-luciferaserats whose body temperature and locomotor activity
      were arrhythmic and from several groups of rhythmic rats held in LD, DD, and
      short-term LL. The authors measured mPer1gene expression by recording light
      output with sensitive photomultipliers. Most of the cultures from all groups
      displayed circadian rhythms. This could reflect persistent rhythmicity in vivo
      prior to culture or, alternatively, rhythmicity that may have been initiated by
      the culture procedure. To test this, the authors cultured tissues at 2 different
      times 12 h apart and asked whether phase of the rhythm was related to culture
      time. The pineal, pituitary, and SCN cultures showed partial or complete
      dependence of phase on culture time, while peak phases of the cornea cultures
      were independent of culture time in rhythmic rats and were randomly distributed
      regardless of culture time in arrhythmic animals. These results suggest that in
      behaviorally arrhythmic rats, oscillators in the pineal, pituitary, and SCN had
      been arrhythmic or severely damped in vivo, while the cornea oscillator was free
      running. The peak phases of the SCN cultures were particularly sensitive to some
      aspect of the culture procedure since rhythmicity of SCN cultures from robustly
      rhythmic LD-entrained rats was strongly influenced when the procedure was carried
      out at any time except the 2nd half of the day.

PMID- 16275771
TI  - Individual differences in rhythms of behavioral sleep and its neural substrates
      in Nile grass rats.
AB  - Laboratory populations of grass rats (Arvicanthis niloticus) housed with a
      running wheel show considerable variation in patterns of locomotor activity. At
      the extremes are "day-active" (DA) animals with a monophasic distribution of
      running throughout the light phase and "night-active" (NA) animals exhibiting a
      biphasic pattern with an extended peak at the beginning of the dark phase and a
      brief peak shortly before lights-on. Here, the authors use this intraspecific
      variation to explore interactions between circadian and homeostatic influences on
      sleep and the effects of these interactions on the activity of brain regions
      involved in sleep regulation. Male animals were singly housed with running wheels
      in a 12:12 LD cycle, videotaped for 24 h, and perfused at ZT 4 or 16. Behavioral
      sleep was scored from the videotapes, and brains were processed for cFos
      immunoreactivity (cFos-ir). Sleep duration within the light and dark phases was
      higher in NA and DA animals, respectively, but these groups did not differ with
      respect to total sleep. In both groups, sleep bouts were shortest in the light
      phase and longest between ZT 20 and ZT 23. In the ventrolateral preoptic area
      (VLPO), cFos-ir was higher at ZT 16 than at ZT 4 in DA but not NA grass rats, and
      it was correlated with behavioral sleep at ZT 16 but not ZT 4. In OXA neurons,
      cFos-ir was high at ZT 4 in DA grass rats and at ZT 16 in NA grass rats, and it
      was correlated with behavioral sleep at both times. In the lower
      subparaventricular zone (LSPV), cFos-ir was higher at ZT 16 in both DA and NA
      animals, and it was unrelated to behavioral sleep. Thus, patterns of cFos-ir in
      the LSPV and OXA neurons were most tightly linked to time and sleep,
      respectively, whereas cFos-ir in the VLPO was influenced by an interaction
      between these 2 variables.

PMID- 16275772
TI  - A separate circadian oscillator controls nocturnal migratory restlessness in the
      songbird Sylvia borin.
AB  - When confined to a cage, migratory songbirds exhibit nocturnal migratory
      restlessness (also called Zugunruhe) during the spring and autumn migratory
      periods, even though these birds are exclusively diurnal during the remainder of
      the year. Zugunruhe, which has been demonstrated to be under the direct control
      of a circannual timer, is characterized by a stereotypic "wing-whirring" behavior
      while the bird is perched. To elucidate the role played by the circadian system
      in the regulation of Zugunruhe, the authors studied the activity of garden
      warblers (Sylvia borin), long-distance nocturnal migrants, under skeleton
      photoperiods of different lengths and under constant dim light. In
      11.5D:1L:10.5D:1L skeleton photoperiods, the authors found that Zugunruhe free
      ran in a substantial proportion of birds, while their normal daily activities
      (e.g., feeding and preening) remained synchronized to 24 h. Some birds expressing
      Zugunruhe under constant dim light continued to show 2 distinct bouts of
      activity: one corresponding to daily activities, the other to wing-whirring. In
      some cases, these 2 bouts crossed while free-running with different periods.
      Birds expressing Zugunruhe also had significantly longer free-running periods
      than birds that did not. The study data suggest that the seasonal appearance of
      Zugunruhe is the result of the interactions of at least 2 circadian oscillators
      and that it is the phase relationship of these 2 oscillators that determines when
      nocturnal migratory restlessness is expressed. Furthermore, these data are
      consistent with the previously proposed internal coincidence hypothesis as a
      model for the ontogeny of circannual rhythms.

PMID- 16275773
TI  - Glucocorticoid administration increases hPer1 mRNA levels in human peripheral
      blood mononuclear cells in vitro or in vivo.

PMID- 16275774
TI  - Rutger Wever: an appreciation.

PMID- 16275778
TI  - Electron diffraction from laser-aligned beams of large hydrated molecules.
AB  - We consider X-ray or electron diffraction from a molecular beam of hydrated
      proteins. These are aligned by the polarized field of a powerful continuous
      infrared laser. The laser power, temperature and molecular size needed to obtain
      sufficient alignment accuracy for sharp diffraction patterns is estimated using a
      thermal average, and the resulting Dawson integral compared with the estimate
      based on equipartition used in our previous work. The conditions determined allow
      sub-nanometer resolution charge-density maps to be reconstructed from phased
      diffraction patterns, so that the secondary structure of the proteins can be
      observed.

PMID- 16275779
TI  - Contrast analysis of dislocation images in TEM-cathodoluminescence technique.
AB  - Monochromatic cathodoluminescence CL images of the threading dislocations in Si
      doped n-GaN were observed by the TEM-CL technique. We studied dependence of the
      contrast and the FWHM of the dislocation image on sample thickness, accelerating
      voltage and temperature. The CL spectra were measured at various temperatures and
      were analyzed to find the property of the band edge (BE) emission used for the CL
      imaging. The observation showed that the FWHM of the dislocation contrast
      monotonically increases with sample thickness and decreases with accelerating
      voltage, which qualitatively agrees with the behavior expected from the theory.
      On the other hand, the temperature dependence of the FWHM shows an anomalous
      behavior. This dependence can be explained by the mobility and lifetime of holes
      as a function of temperature. The relation between the FWHM of the dislocation
      contrast and the diffusion length is also discussed.

PMID- 16275780
TI  - Characterization of charging in semiconductor device materials by electron
      holography.
AB  - Quantitative analysis of electrostatic potential in semiconductor device samples
      using off-axis electron holography in the electron microscope is complicated by
      the presence of charged insulating layers. Preliminary results indicate that the
      behavior of p-type material near the Si-insulator interface may differ from that
      of n-type if the insulator is charging. Coating one side of the sample surface
      with carbon usually eliminates charging effects. Holographic phase measurements
      on thin silicon oxide film at liquid nitrogen temperature indicates that the
      maximum electric field near the edge of an charged region is 18 MV cm(-1), on the
      order of the breakdown voltage.

PMID- 16275781
TI  - An analysis of the feasibility of short read sequencing.
AB  - Several methods for ultra high-throughput DNA sequencing are currently under
      investigation. Many of these methods yield very short blocks of sequence
      information (reads). Here we report on an analysis showing the level of genome
      sequencing possible as a function of read length. It is shown that re-sequencing
      and de novo sequencing of the majority of a bacterial genome is possible with
      read lengths of 20-30 nt, and that reads of 50 nt can provide reconstructed
      contigs (a contiguous fragment of sequence data) of 1000 nt and greater that
      cover 80% of human chromosome 1.

PMID- 16275782
TI  - Farm animal genomics and informatics: an update.
AB  - Farm animal genomics is of interest to a wide audience of researchers because of
      the utility derived from understanding how genomics and proteomics function in
      various organisms. Applications such as xenotransplantation, increased livestock
      productivity, bioengineering new materials, products and even fabrics are several
      reasons for thriving farm animal genome activity. Currently mined in rapidly
      growing data warehouses, completed genomes of chicken, fish and cows are
      available but are largely stored in decentralized data repositories. In this
      paper, we provide an informatics primer on farm animal bioinformatics and genome
      project resources which drive attention to the most recent advances in the field.
      We hope to provide individuals in biotechnology and in the farming industry with
      information on resources and updates concerning farm animal genome projects.

PMID- 16275783
TI  - Statistical evidence for conserved, local secondary structure in the coding
      regions of eukaryotic mRNAs and pre-mRNAs.
AB  - Owing to the degeneracy of the genetic code, protein-coding regions of mRNA
      sequences can harbour more than only amino acid information. We search the mRNA
      sequences of 11 human protein-coding genes for evolutionarily conserved secondary
      structure elements using RNA-Decoder, a comparative secondary structure
      prediction program that is capable of explicitly taking the known protein-coding
      context of the mRNA sequences into account. We detect well-defined, conserved RNA
      secondary structure elements in the coding regions of the mRNA sequences and show
      that base-paired codons strongly correlate with sparse codons. We also
      investigate the role of repetitive elements in the formation of secondary
      structure and explain the use of alternate start codons in the caveolin-1 gene by
      a conserved secondary structure element overlapping the nominal start codon. We
      discuss the functional roles of our novel findings in regulating the gene
      expression on mRNA level. We also investigate the role of secondary structure on
      the correct splicing of the human CFTR gene. We study the wild-type version of
      the pre-mRNA as well as 29 variants with synonymous mutations in exon 12. By
      comparing our predicted secondary structures to the experimentally determined
      splicing efficiencies, we find with weak statistical significance that pre-mRNAs
      with high-splicing efficiencies have different predicted secondary structures
      than pre-mRNAs with low-splicing efficiencies.

PMID- 16275784
TI  - Structure-function analysis of yeast RNA debranching enzyme (Dbr1), a manganese
      dependent phosphodiesterase.
AB  - Saccharomyces cerevisiae Dbr1 is a 405-amino acid RNA debranching enzyme that
      cleaves the 2'-5' phosphodiester bonds of the lariat introns formed during pre
      mRNA splicing. Debranching appears to be a rate-limiting step for the turnover of
      intronic RNA, insofar as the steady-state levels of lariat introns are greatly
      increased in a Deltadbr1 strain. To gain insight to the requirements for yeast
      Dbr1 function, we performed a mutational analysis of 28 amino acids that are
      conserved in Dbr1 homologs from other organisms. We identified 13 residues
      (His13, Asp40, Arg45, Asp49, Tyr68, Tyr69, Asn85, His86, Glu87, His179, Asp180,
      His231 and His233) at which alanine substitutions resulted in lariat intron
      accumulation in vivo. Conservative replacements at these positions were
      introduced to illuminate structure-activity relationships. Residues important for
      Dbr1 function include putative counterparts of the amino acids that comprise the
      active site of the metallophosphoesterase superfamily, exemplified by the DNA
      phosphodiesterase Mre11. Using natural lariat RNAs and synthetic branched RNAs as
      substrates, we found that mutation of Asp40, Asn85, His86, His179, His231 or
      His233 to alanine abolishes or greatly diminishes debranching activity in vitro.
      Dbr1 sediments as a monomer and requires manganese as the metal cofactor for
      debranching.

PMID- 16275785
TI  - DNA damage and replication stress induced transcription of RNR genes is dependent
      on the Ccr4-Not complex.
AB  - Genetic experiments have indicated a role for the Ccr4-Not complex in the
      response to hydroxyurea (HU) induced replication stress and ionizing radiation in
      yeast. This response includes transcriptional induction of the four genes
      constituting the ribonucleotide reductase (RNR) enzymatic complex, RNR1-4 and
      degradation of its inhibitor, Sml1p. The Ccr4-Not complex has originally been
      described as a negative regulator of RNA polymerase II (pol II) transcription,
      but it has also been implicated in mRNA turnover and protein ubiquitination. We
      investigated the mechanism of the HU sensitivity conferred by mutation of CCR4
      NOT genes. We found that the ubiquitin protein ligase activity of Not4p does not
      play a role in HU induced Sml1p degradation. We show, however, that the HU
      sensitivity of ccr4-not mutant strains correlated very well with a defect in
      accumulation of RNR2, RNR3 and RNR4 mRNA after HU or methyl-methane sulfonate
      (MMS) treatment. Chromatin immunoprecipitation (ChIP) experiments show that TBP,
      pol II and Set1p recruitment to the activated RNR3 locus is defective in cells
      lacking NOT4. Moreover, RNR3-promoter activity is not induced by HU in these
      cells. Our experiments show that induction of RNR gene transcription is defective
      in ccr4-not mutant strains, providing an explanation for their sensitivity to HU.

PMID- 16275788
TI  - Disparities in the financial burden of children's healthcare expenditures.
AB  - OBJECTIVE: To examine whether income-related disparities in the burden of
      children's out-of-pocket health care expenditures have diminished with the
      expansions in public insurance for children in low-income families. DESIGN: We
      compared absolute financial burden (out-of-pocket expenditures per child) and
      relative financial burden (out-of-pocket expenditures per child as a proportion
      of family income) among children aged 0 to 18 years in 6 poverty level groups
      using the 1980 National Medical Care Utilization and Expenditure Survey and the
      2000 Medical Expenditure Panel Survey. Regression models were used to assess
      whether disparities in financial burden diminished between 1980 and 2000.
      RESULTS: There were significant reductions (P<.01) in absolute burden over time
      for children above 200% of the federal poverty level. Relative financial burden
      decreased significantly (P<.01) for all of the income groups, ranging from a
      reduction of 36.49% for those below 100% of the federal poverty level (95% CI, 
      49.54% to -20.07%) to a reduction of 46.69% for those at or above 300% of the
      federal poverty level (95% CI, -54.43% to -37.62%). For low-income children,
      relative financial burden was 49.49% less with public insurance (95% CI, -66.24%
      to -24.35%) and 79.14% greater with private insurance (95% CI, 9.31% to 193.59%)
      than relative financial burden for low-income children without insurance.
      CONCLUSIONS: While the financial burden of children's out-of-pocket health care
      expenditures has decreased for all of the income groups over time, socioeconomic
      disparities persist. However, public insurance coverage appears to mitigate the
      financial burden for low-income children.

PMID- 16275786
TI  - Genome dynamics and diversity of Shigella species, the etiologic agents of
      bacillary dysentery.
AB  - The Shigella bacteria cause bacillary dysentery, which remains a significant
      threat to public health. The genus status and species classification appear no
      longer valid, as compelling evidence indicates that Shigella, as well as
      enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and
      form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes
      deadly epidemics but Shigella boydii is restricted to the Indian subcontinent,
      while Shigella flexneri and Shigella sonnei are prevalent in developing and
      developed countries respectively. To begin to explain these distinctive
      epidemiological and pathological features at the genome level, we have carried
      out comparative genomics on four representative strains. Each of the Shigella
      genomes includes a virulence plasmid that encodes conserved primary virulence
      determinants. The Shigella chromosomes share most of their genes with that of
      E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300 approximately
      700 copies of insertion sequence (IS) elements, and numerous deletions,
      insertions, translocations and inversions. There is extensive diversity of
      putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene
      transfer. Hence, via convergent evolution involving gain and loss of functions,
      through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements
      and formation of pseudogenes, the Shigella spp. became highly specific human
      pathogens with variable epidemiological and pathological features.

PMID- 16275789
TI  - Prevalence and risk factors for hepatitis C virus infection among adolescents in
      detention.
AB  - OBJECTIVE: To assess the prevalence and correlates of hepatitis C virus infection
      in a sample of detained adolescents. DESIGN/SETTING/PARTICIPANTS: Cross-sectional
      prevalence study with 10- to 18-year-old adolescents who were consecutively
      admitted to a juvenile detention center in San Antonio, Tex. MAIN OUTCOME
      MEASURES: The prevalence of hepatitis C virus infection and associated risk
      factors. RESULTS: Of the 1002 participants, 75% were Hispanic and the mean age
      was 15 years. Twenty adolescents had laboratory data consistent with hepatitis C
      virus infection, giving an overall prevalence of 2.0% (95% confidence interval,
      1.2-3.1). All adolescents infected with hepatitis C virus were Hispanic (13 boys
      and 7 girls). Although a high proportion of the participants reported having had
      intranasal drug use (55.6%), tattooing (50.5%), or body piercing (25.3%), the
      only factor significantly associated with hepatitis C virus infection was having
      a history of injection drug use. Injection drug use was reported by 5.3% of the
      participants but by 95% (19/20) of those infected with the hepatitis C virus.
      CONCLUSIONS: This study indicates that injection drug use was linked with the
      majority of hepatitis C virus infections in this population of detained
      adolescents, similar to findings in adults. These adolescents reported a high
      frequency of other behaviors that could potentially pose a risk for contracting
      bloodborne infections. Effective prevention and awareness programs in a detention
      setting need to be comprehensive and include screening, hepatitis A and B
      immunizations, and risk-reduction counseling.

PMID- 16275790
TI  - Transmission of monkeypox among persons exposed to infected prairie dogs in
      Indiana in 2003.
AB  - OBJECTIVE: To describe a cluster of human monkeypox cases associated with
      exposure to ill prairie dogs in a home child care. DESIGN, SETTING, PARTICIPANTS:
      We identified all persons exposed to 2 pet prairie dogs in County A, Indiana;
      performed active surveillance for symptomatic monkeypox infection; and evaluated
      the types of exposure that may have resulted in infection. For children who
      attended the child care where the animals were housed, we also measured the rate
      of seroconversion to monkeypox virus. MAIN OUTCOME MEASURES: Nine (13%) of 70
      persons exposed to the prairie dogs reported signs and symptoms of monkeypox. Two
      (40%) of 5 symptomatic child care attendees reported direct contact with the
      prairie dogs. Two (13%) of 15 child care attendees evaluated tested positive for
      IgM antibodies against orthopoxvirus; both reported symptoms consistent with
      monkeypox. RESULTS: The risk of symptomatic infection correlated with the time
      and intensity of animal exposure, which was 100% (4/4) among family members with
      extensive direct contact, 19% (5/26) among the veterinarian and nonfamily child
      care attendees with moderate exposure, and 0% (0/40) among school children with
      limited exposure (P<.01). CONCLUSIONS: Monkeypox virus was transmitted from ill
      prairie dogs in a child care and veterinary facilities. The risk of symptomatic
      infection correlated with the amount of exposure to the prairie dogs. Although
      most cases of human monkeypox were associated with direct animal contact, other
      routes of transmission cannot be excluded.

PMID- 16275791
TI  - Bullying, psychosocial adjustment, and academic performance in elementary school.
AB  - BACKGROUND: Over the past decade, concerns about bullying and its role in school
      violence, depression, and health concerns have grown. However, no large studies
      in the United States have examined the prevalence of bullying during elementary
      school or its association with objective measures of school attendance and
      achievement. OBJECTIVE: To determine the prevalence of bullying during elementary
      school and its association with school attendance, academic achievement,
      disciplinary actions, and self-reported feelings of sadness, safety, and
      belonging. DESIGN: Cross-sectional study using 2001-2002 school data. SETTING:
      Urban, West Coast public school district. PARTICIPANTS: Three thousand five
      hundred thirty (91.4%) third, fourth, and fifth grade students. MAIN OUTCOME
      MEASURE: Self-reported involvement in bullying. RESULTS: Twenty-two percent of
      children surveyed were involved in bullying either as a victim, bully, or both.
      Victims and bully-victims were more likely to have low achievement than
      bystanders (odds ratios [ORs], 0.8 [95% confidence interval (CI), 0.7-0.9] and
      0.8 [95% CI, 0.6-1.0], respectively). All 3 bullying-involved groups were
      significantly more likely than bystanders to feel unsafe at school (victims, OR,
      2.1 [95% CI, 1.1-4.2]; bullies, OR, 2.5 [95% CI, 1.5-4.1]; bully-victims, OR, 5.0
      [95% CI, 1.9-13.6]). Victims and bully-victims were more likely to report feeling
      that they don't belong at school (ORs, 4.1 [95% CI, 2.6-6.5] and 3.1 [95% CI, 1.3
      7.2], respectively). Bullies and victims were more likely than bystanders to feel
      sad most days (ORs 1.5 [95% CI, 1.2-1.9] and 1.8 [95% CI, 1.2-2.8],
      respectively). Bullies and bully-victims were more likely to be male (ORs, 1.5
      [95% CI, 1.2-1.9] and 3.0 [95% CI, 1.3-7.0], respectively). CONCLUSIONS: The
      prevalence of frequent bullying among elementary school children is substantial.
      Associations between bullying involvement and school problems indicate this is a
      serious issue for elementary schools. The research presented herein demonstrates
      the need for evidence-based antibullying curricula in the elementary grades.

PMID- 16275792
TI  - Effect of chorioamnionitis on neurodevelopmental outcome in preterm infants.
AB  - OBJECTIVE: To assess the association of neurodevelopmental outcome with the
      placental diagnosis of chorioamnionitis in very low-birth-weight infants.
      METHODS: One hundred seventy-seven surviving very low-birth-weight infants, 22 to
      29 weeks' gestational age, born after varying severity of chorioamnionitis, were
      evaluated at a mean +/- SD age of 19 +/- 6 months' corrected age with Bayley
      Scales of Infant Development II and neurologic examination. Select maternal and
      infant variables were abstracted from the medical records. Neonatal morbidities,
      Mental Developmental Index (MDI) score, Psychomotor Developmental Index (PDI)
      score, probability of normal MDI and PDI scores (>84), and cerebral palsy between
      the chorioamnionitis and the control groups were assessed, controlling for
      gestational age, sex, and the maternal use of steroids and antibiotics. RESULTS:
      The chorioamnionitis group of 102 infants was compared with 75 control infants
      (mean +/- SD birth weight, 947 +/- 236 g and 966 +/- 219 g, respectively; mean +/
      SD gestational age, 26.1 +/- 2.8 weeks and 27.1 +/- 1.5 weeks, respectively).
      Infants with chorioamnionitis, compared with controls, had a significantly higher
      incidence of intraventricular hemorrhage (30% vs 13%) and retinopathy of
      prematurity (68% vs 42%). Cerebral palsy was diagnosed in 8.6% of the infants
      with chorioamnionitis and 6.6% of the controls. The MDI and PDI scores were
      similar between the chorioamnionitis and control groups (mean +/- SD MDI score,
      96 +/- 16 vs 97 +/- 18 and mean +/- SD PDI score, 94 +/- 19 vs 92 +/- 19,
      respectively). CONCLUSIONS: In very low-birth-weight infants we found a higher
      incidence of intraventricular hemorrhage and retinopathy of prematurity but
      similar MDI and PDI scores and risk of cerebral palsy associated with
      chorioamnionitis.

PMID- 16275793
TI  - Negative results and impact factor: a lesson from neonatology.
AB  - OBJECTIVE: To test the hypothesis that articles with negative results are more
      likely than articles with positive results to be published in journals with lower
      impact factor. DESIGN AND SETTING: We selected all of the randomized, placebo
      controlled trials conducted during the neonatal period between October 1, 1998,
      and October 1, 2003. Trials were classified as having positive results or
      negative results (significant or no significant difference, respectively). Only
      studies dealing with primary outcomes (efficacy) were included. MAIN OUTCOME
      MEASURES: The impact factor of each journal was determined, and the sample size
      for each study was noted. RESULTS: There were 233 articles that fulfilled the
      inclusion criteria. There was a significant difference between the 2 groups in
      terms of impact factor (P = .03) but not sample size (P = .30). Impact factor
      correlated with both sample size and the type of study results (positive results
      vs negative results; P<.05). CONCLUSION: Articles with negative results are more
      likely than articles with positive results to be published in journals with lower
      impact factor.

PMID- 16275794
TI  - Iron deficiency, prolonged bottle-feeding, and racial/ethnic disparities in young
      children.
AB  - BACKGROUND: Childhood iron deficiency is associated with behavioral and cognitive
      delays. Few studies have explored the relationship between prolonged bottle
      feeding and iron-deficiency anemia among toddlers. OBJECTIVE: To examine the
      association between prolonged bottle-feeding and iron deficiency in a nationally
      representative sample of children ages 1 to 3 years. DESIGN AND METHODS: The
      National Health and Nutrition Examination Survey III provides data on the feeding
      practices of children 1 to 3 years old and contains measures of iron status
      including transferrin saturation, free erythrocyte protoporphyrin, and serum
      ferritin. The prevalence of iron deficiency and duration of bottle-feeding were
      determined for black, white, and Mexican American toddlers. Bivariate and
      multivariate analyses were performed to examine the association between bottle
      feeding duration and iron deficiency. RESULTS: Among 2121 children ages 1 to 3
      years, the prevalence of iron deficiency was 6% among whites, 8% among blacks,
      and 17% among Mexican Americans (P< .001). With increasing duration of bottle
      feeding, the prevalence of iron deficiency among all children increased (3.8%,
      bottle-fed < or =12 months; 11.5%, bottle-fed 13-23 months; and 12.4%, bottle-fed
      24-48 months [P< .001]). At 24 to 48 months of age, 36.8% of Mexican American
      children were still bottle-fed, compared with 16.9% of white and 13.8% of black
      children. In multivariate analyses, bottle-feeding for 24 to 48 months and
      Mexican ethnicity were associated with iron deficiency (odds ratio, 2.8; 95%
      confidence interval, 1.3-6.0; and odds ratio, 2.9; 95% confidence interval, 1.5
      5.6, respectively). CONCLUSIONS: Children with prolonged bottle-feeding and
      Mexican American children are at higher risk for iron deficiency. Screening
      practices and nutritional counseling should be targeted at these high-risk
      groups.

PMID- 16275795
TI  - Lipoid pneumonia due to Mexican folk remedies: cultural barriers to diagnosis.
AB  - OBJECTIVE: To describe 2 cases of lipoid pneumonia in Mexican American infants
      after administration of vegetable- or animal-derived oils and the cultural
      barriers to diagnosis. Various folk remedies have been documented in the
      international medical literature that involve the oral or nasal administration of
      vegetable- or animal-derived oils to children for the treatment of common
      ailments, including nasal stuffiness, constipation, and colic. Lipoid pneumonia
      is a known complication of such practices in Mexico, India, Saudi Arabia, and
      other countries. METHODS: Case reports of 2 Mexican American infants with
      respiratory distress and interviews with 30 immigrant families of Mexican origin.
      RESULTS: In both cases, language and cultural barriers resulted in a delayed
      diagnosis of lipoid pneumonia. Interviews with immigrant families confirmed that
      oil administration to children is a common traditional therapy in Mexican
      cultures. CONCLUSIONS: These findings underscore the need for primary care
      providers to be aware of the traditional practice of oil administration to
      infants in many cultures, its pathophysiological consequences, the potential
      cultural barriers to timely diagnosis, and the opportunity to prevent cases of
      lipoid pneumonia through anticipatory guidance.

PMID- 16275796
TI  - Effectiveness of gun-safety counseling and a gun lock giveaway in a Hispanic
      community.
AB  - OBJECTIVE: To evaluate the effectiveness of gun-safety counseling, a gun-safety
      brochure, and a free gun lock in subsequent gun removal and safe storage.
      METHODS: In a predominantly Hispanic pediatric clinic, gun-owning families were
      identified and assigned to either an intervention group (gun-safety counseling,
      gun-safety brochure, and a free gun lock) or a control group (usual anticipatory
      guidance). Families were resurveyed 1 month later for changes in the proportion
      of gun owners, changes in frequency of unloaded and locked gun storage, and
      changes to the use of locked storage. RESULTS: Two hundred six (7.8%) of the 2649
      parents initially surveyed kept guns in their households. At follow-up, 16% of
      the control group removed all guns from their homes as compared with 22% of the
      intervention group (P = .41). Among the families who received the intervention,
      61.6% either removed all guns from their homes or improved their gun storage
      safety practice in some way. Only 26.9% of the families in the control group
      showed similar types of improvement (P<.001). In those households still with guns
      at follow-up, 50.9% of the intervention group had some type of improvement in
      safe gun storage compared with 12.3% of the control group (P<.001). More
      specifically, 25.0% in the intervention group improved the frequency of locked
      storage of guns compared with 4.8% of those in the control group (P = .003).
      Twenty-six percent of the intervention group improved the use of locked storage
      compared with 3.1% in the control group (P<.001). CONCLUSIONS: A brief gun-safety
      counseling session supported with written information along with a gun lock
      giveaway resulted in significant improvements in safe gun storage behaviors. It
      did not significantly influence the removal of guns from the home. This study
      gives support to the recommendations of the American Academy of Pediatrics (Elk
      Grove Village, Ill) and other professional organizations to discuss gun safety
      with families and encourages research in this area. It also suggests that
      providing tools such as gun locks to enable the desired behavior may improve safe
      storage.

PMID- 16275797
TI  - Management of influenza symptoms in healthy children: cost-effectiveness of rapid
      testing and antiviral therapy.
AB  - OBJECTIVE: To determine the cost-effectiveness of rapid testing and antiviral
      therapy for children of different ages with symptoms of influenza. DESIGN: Cost
      effectiveness analysis from the societal perspective using a decision model based
      on published data. SETTING: Physician's office during an influenza A epidemic.
      PARTICIPANTS: Hypothetical children aged 2, 7, and 15 years. INTERVENTIONS: Rapid
      testing or clinical diagnosis followed by treatment with amantadine hydrochloride
      or oseltamivir phosphate compared with no antiviral therapy. OUTCOME MEASURES:
      Costs and quality-adjusted life expectancy. RESULTS: Empirical therapy with
      antiviral medication resulted in the greatest quality-adjusted life expectancy in
      all age groups. Compared with not treating, antiviral therapy improved quality
      adjusted life expectancy by 0.003 quality-adjusted life-year by shortening the
      duration of illness and preventing otitis media. In young children it saved up to
      USD 121 per child mostly by avoiding parental work loss. Excluding work loss,
      antiviral therapy improved quality-adjusted life expectancy at a cost of USD 800
      to 1800 per quality-adjusted life-year saved. Compared with amantadine,
      oseltamivir was not cost-effective when influenza A predominated. The incremental
      cost-effectiveness of oseltamivir fell below USD 50 000 per quality-adjusted life
      year saved when the proportion of influenza B exceeded 14% for a 2-year-old, 27%
      for a 7-year-old, or 43% for a 15-year-old. Rapid testing was cost-effective only
      when the probability of influenza was 60% or less. CONCLUSIONS: For children
      presenting with influenza symptoms during a local influenza outbreak, treatment
      with antiviral therapy appears to offer the best outcome and often saves money.
      The choice of antiviral drug should be based on the prevalence of influenza B.

PMID- 16275798
TI  - Normality of cardiopulmonary capacity in children operated on to correct
      congenital heart defects.
AB  - BACKGROUND: One of the main goals of corrective surgery of congenital heart
      defects in children is the improvement of quality of life, which in young
      children is predominantly determined by exercise capacity. It is not known
      whether this goal can be achieved in school-aged children who have undergone
      cardiac surgery in infancy. OBJECTIVES: To determine if primary school-aged
      children who underwent surgery to correct congenital heart defects in infancy are
      physically as fit as their peers. METHODS: We examined 84 children with
      congenital heart defects, aged 4 to 11 years, after surgical repair. Fifty-two
      children had simple defects (ie, atrial or ventricular septal defect, coarctation
      of the aorta). Thirty-two children had complex defects (ie, tetralogy of Fallot,
      pulmonary atresia with ventricular septal defect). All patients underwent
      exercise testing performed on a specially modified bicycle ergometer. Ninety
      eight sex- and age-matched healthy children served as the control group. RESULTS:
      There was no gender difference, either in healthy children or in the group with
      congenital heart defects, regarding exercise testing and that the healthy
      children reached a mean +/- SD normalized maximal performance of 2.8 +/- 0.3
      W/kg. The same range was found for the children who had undergone surgery to
      correct simple heart defects. The children operated on to correct complex heart
      defects showed significantly impaired mean normalized maximal performance,
      although this tended to be lower in the group that had pulmonary atresia with a
      ventricular septal defect than in the group with tetralogy of Fallot (mean
      normalized maximal performance, 1.9 W/kg vs 2.3 W/kg). CONCLUSIONS: The goal of
      normal exercise capacity in childhood after heart surgery is achieved in those
      with simple heart defects only. In children with complex heart defects impaired
      exercise performance persists, depending on the severity of the heart defect and
      probably on chronotropic incompetence.

PMID- 16275799
TI  - Effect of pectus excavatum deformity on cardiorespiratory fitness in adolescent
      boys.
AB  - OBJECTIVE: To determine the magnitude of the effects of pectus excavatum
      deformity on endurance fitness and cardiorespiratory functional reserve in
      adolescent boys. DESIGN: Cross-sectional comparison of cardiac and ventilatory
      variables at rest and during a maximal cycle exercise test. SETTING: Pediatric
      exercise-testing laboratory. PARTICIPANTS: Twelve boys (mean +/- SD age, 14.1 +/-
      1.8 years; age range, 11.8-18.0 years) with moderate-to-severe pectus excavatum
      deformity (mean +/- SD Haller index, 3.95 +/- 0.88) and 20 control boys (mean +/-
      SD age, 12.5 +/- 0.4 years; age range, 12.1-13.5 years) without musculoskeletal
      deformity. MAIN OUTCOME MEASURES: Endurance fitness (physical work capacity);
      respiratory rate, tidal volume, and minute ventilation; and cardiac output and
      stroke volume by Doppler echocardiography. RESULTS: Patients with pectus
      deformity had significantly lower endurance fitness than controls (mean +/- SD
      physical work capacity, 2.60 +/- 0.28 W . kg(-1) vs 3.11 +/- 0.45 W . kg(-1)) and
      reduced mean +/- SD values for maximal cardiac index (10.6 +/- 1.6 L . min(-1) vs
      12.0 +/- 2.2 L . min(-1)) and peak tidal volume (3.02 +/- 0.27 mL . kg(-1) . 10(
      2) vs 3.46 +/- 0.30 mL . kg(-1) . 10(-2)). However, considerable overlap was
      observed in these values between the 2 groups. CONCLUSIONS: As a group, boys with
      pectus excavatum deformity have lower endurance fitness than controls, and this
      is associated with reduced cardiac output and tidal volume responses to exercise.
      However, the wide variability of these measures makes it difficult to assign
      pectus deformity as a cause of exercise intolerance in individual patients.

PMID- 16275800
TI  - Acute traumatic stress symptoms in child occupants and their parent drivers after
      crash involvement.
AB  - BACKGROUND: Approximately 1 in 4 children hospitalized with injuries from traffic
      crashes and their parents experience symptoms of acute stress disorder (ASD).
      These families represent a minority of those exposed to the trauma of a crash. To
      date, no studies have explored the prevalence of ASD symptoms in the broader
      population of children and parents exposed to crashes. OBJECTIVE: To describe the
      prevalence of and risk factors for ASD symptoms in children and their driver
      parents after vehicle crashes. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional
      study via telephone survey of parent drivers and children (aged 5-15 years),
      using an exposure-based crash surveillance system. A probability sample of 1091
      crashes involving 1483 children weighted to represent 24 376 children in 18 422
      crashes was collected. MAIN OUTCOME MEASURE(S): Parent-reported ASD symptoms and
      impairment. RESULTS: Significant ASD symptoms occurred in 1.6% (95% confidence
      interval, 0.9%-2.3%) of children in crashes and 4.7% (95% confidence interval,
      4.0%-5.5%) of parents. In children, ASD symptoms were independently associated
      with sustaining an injury and with receiving medical care; in parents, symptoms
      were independently associated with child injury, child receiving medical care,
      Hispanic ethnicity, lower income (< USD 40 000), and higher crash severity.
      CONCLUSIONS: Sustaining injuries and receiving medical treatment were strong
      predictors for developing ASD symptoms after crashes but ASD symptoms often
      occurred in the absence of these risk factors. Health care professionals should
      consider screening for traumatic stress symptoms in children and their parents
      when children are involved in traffic crashes, particularly if they sustain
      injuries.

PMID- 16275801
TI  - Our porous safety net for children.

PMID- 16275802
TI  - Firearm injury prevention: reasons for optimism.

PMID- 16275803
TI  - Writing abstracts for journal articles.

PMID- 16275804
TI  - Fatal syncope-related fall after immunization.

PMID- 16275805
TI  - The Mediterranean at Genoa.

PMID- 16275806
TI  - Translational research on the way to effective therapy for Alzheimer disease.
AB  - CONTEXT: Alzheimer disease (AD) is a major public health issue with a prediction
      of 12 million Americans being affected by 2025 from the present 4 million.
      Molecular and genetic findings have provided significant insights into the roles
      that amyloid, tau, and apolipoprotein E isoforms have in the causation of AD. A
      central issue in AD pathogenesis is the amyloid cascade hypothesis. It states
      that abnormal amyloid processing and accumulation is the primary causative factor
      of AD and other associated neuropathologic abnormalities are of secondary
      consequence. It is presented to provide the rationale for novel drug and
      vaccination therapeutic strategies. Future research directed at prediction and
      prevention of AD through a genomic and proteomic analysis with identification of
      multiple polymorphic genes that interact, resulting in increased risk for late
      onset AD, are the realistic and ultimate goals. A new approach for drug
      development is required, one that will emphasize a genomic and proteomic analysis
      to identify at-risk gene sets whose genetic expression is sufficient to cause
      late onset, sporadic AD. Prediction and prevention of disease prior to clinical
      signs and symptoms are the goals. OBJECTIVE: A review and analysis from
      electronic literature databases and subsequent reference searches of the
      molecular genetic data. including pertinent genetic mutations and abnormal
      biochemical findings causal of AD, are cited. The amyloid cascade hypothesis, the
      contributions of apolipoprotein E, and hyperphosphorylated tau are discussed as
      to their roles in pathogenesis. Molecular targets for potential drug and
      vaccination therapies are cited from a critical assessment of the molecular and
      biomedical data. These data form the basis for rational, target-specific drug and
      vaccination therapies currently employed and planned for the near future. Phase 2
      and 3 clinical trial results of drug and vaccination therapies are cited.
      CONCLUSIONS: A new approach is needed as current pharmacologic therapy directed
      at symptomatic relief has proved to be marginally effective. The genomic and
      proteomic basis of AD will be defined in the near future, and corresponding
      molecular therapeutic targets will be identified. Genomic neurology has arrived
      and its application to resolving AD is our best hope.

PMID- 16275807
TI  - Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a
      randomized, double-blind, placebo-controlled study.
AB  - CONTEXT: Agents that enhance N-methyl-D-aspartate (NMDA) function through the
      glycine modulatory site (D-serine, glycine, or D-cycloserine) or through glycine
      transporter 1 (sarcosine) improve the symptoms of patients with stable chronic
      schizophrenia. OBJECTIVE: To determine whether NMDA-glycine site agonists or
      glycine transporter-1 inhibitors have better efficacy and whether NMDA receptor
      enhancing agents have beneficial effects for acute exacerbation of schizophrenia.
      DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Inpatient
      units of 2 major medical centers in Taiwan. Patients Sixty-five schizophrenic
      inpatients with acute exacerbation. INTERVENTIONS: Six weeks of treatment with
      sarcosine (2 g/d), D-serine (2 g/d), or placebo and concomitant optimal
      risperidone therapy. MAIN OUTCOME MEASURES: Positive and Negative Syndrome Scale
      (PANSS) and Scale for the Assessment of Negative Symptoms (SANS) (20 and 17
      items) total scores. RESULTS: The sarcosine group revealed more reductions in
      PANSS total scores than the placebo (P = .04) and D-serine (P<.001) groups.
      Sarcosine adjunctive treatment was also superior to placebo in reducing SANS-20
      (P = .007) and SANS-17 (P = .003) scores and to D-serine in decreasing SANS-20 (P
      = .006) and SANS-17 (P = .002) scores. The PANSS-general, PANSS-cognitive, and
      PANSS-depressive symptoms scores and SANS-alogia and SANS-blunted affect scores
      improved significantly more in sarcosine-cotreated patients than in risperidone
      monotherapy patients (P< or =.02 for all). Sarcosine adjunctive therapy also
      surpassed D-serine in terms of PANSS-general, PANSS-positive, PANSS-negative, and
      PANSS-depressive symptoms scores (P< or =.04 for all). D-serine and risperidone
      cotreatment did not differ significantly from risperidone monotherapy in all
      efficacy domains. CONCLUSIONS: This first short-term treatment study on NMDA
      receptor-enhancing agents suggests that sarcosine, superior to D-serine, can
      benefit not only patients with long-term stable disease but also acutely ill
      persons with schizophrenia. This finding indicates that a glycine transporter 1
      inhibitor may be more efficacious than NMDA-glycine site agonists for adjuvant
      treatment of schizophrenia, at least during the acute phase. Further studies are
      needed.

PMID- 16275808
TI  - Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray
      matter, and impaired short- and long-term memory.
AB  - CONTEXT: Chromosome 1q42 is among several genomic regions showing replicated
      evidence of linkage with schizophrenia, but the specific susceptibility
      mechanisms underlying this relationship remain to be identified. OBJECTIVE: To
      examine a series of haplotype blocks of single-nucleotide polymorphic markers
      from a segment of 1q42 spanning the disrupted-in-schizophrenia 1 (DISC1) and
      translin-associated factor X (TRAX) genes for association with schizophrenia and
      several endophenotypic traits thought to be involved in disease pathogenesis.
      DESIGN: Population-based twin cohort study. SETTING: Finland. PARTICIPANTS: Two
      hundred thirty-six subjects, consisting of 7 twin pairs concordant for
      schizophrenia (6 monozygotic [MZ] and 1 dizygotic [DZ]), 52 pairs discordant for
      schizophrenia (20 MZ and 32 DZ), and 59 demographically balanced normal pairs (28
      MZ and 31 DZ), were drawn from a twin cohort consisting of all of the same-sex
      twins born in Finland from 1940 through 1957. MAIN OUTCOME MEASURES: Psychiatric
      diagnosis, performance on neurocognitive tests of short- and long-term memory,
      and gray matter volume measurements taken from high-resolution magnetic resonance
      images. RESULTS: A common haplotype incorporating 3 single-nucleotide polymorphic
      markers near the translocation break point of DISC1 (odds ratio, 2.6 [P = .02])
      and a rare haplotype incorporating 4 markers from the DISC1 and TRAX genes (odds
      ratio, 13.0 [P = .001]) were significantly overrepresented among individuals with
      schizophrenia. These haplotypes were also associated with several quantitative
      endophenotypic traits previously observed to covary with schizophrenia and
      genetic liability to schizophrenia, including impairments in short- and long-term
      memory functioning and reduced gray matter density in the prefrontal cortex, as
      demonstrated using a population-based brain atlas method, with a trend toward
      association with reduced hippocampal volume. CONCLUSIONS: Specific alleles of the
      DISC1 and TRAX genes on 1q42 appear to contribute to genetic risk for
      schizophrenia through disruptive effects on the structure and function of the
      prefrontal cortex, medial temporal lobe, and other brain regions. These effects
      are consistent with their production of proteins that play roles in neuritic
      outgrowth, neuronal migration, synaptogenesis, and glutamatergic
      neurotransmission.

PMID- 16275809
TI  - Whole-brain morphometric study of schizophrenia revealing a spatially complex set
      of focal abnormalities.
AB  - CONTEXT: Neuroanatomic abnormalities in schizophrenia may underlie behavioral
      manifestations. Characterization of such abnormalities is required for
      interpreting functional data. Frontotemporal abnormalities have been documented
      by using predetermined region-of-interest approaches, but deformation-based
      morphometry permits examination of the entire brain. OBJECTIVES: To perform whole
      brain analyses of structural differences between patients with schizophrenia and
      controls, to examine sex and medication effects, and to apply a high-dimensional
      nonlinear pattern classification technique to quantify the degree of separation
      between patients and controls, thereby testing the potential of this new
      technique as an aid to diagnostic procedures. DESIGN: Whole-brain morphologic
      analysis using high-dimensional shape transformations. SETTING: Schizophrenia
      Research Center, University of Pennsylvania Medical Center. PARTICIPANTS:
      Neuroleptic-naive and previously treated patients with DSM-IV schizophrenia (n =
      69) and sociodemographically matched controls (n = 79). MAIN OUTCOME MEASURES:
      Gray matter, white matter, and ventricular cerebrospinal fluid volumes in the
      brain. RESULTS: Magnetic resonance images showed reduced gray matter and
      increased ventricular cerebrospinal fluid volumes in patients with schizophrenia
      in the whole brain and in specific foci: the hippocampus and adjacent white
      matter, the cingulate and orbitofrontal cortex, the frontotemporal and
      parietotemporal areas, and the occipital areas near the lingual gyrus. The
      classifier had a mean classification accuracy of 81.1% for men and women combined
      (82% for women and 85% for men, when each group was treated separately),
      determined via cross-validation. CONCLUSIONS: This study confirms previous
      findings of reduced frontotemporal volumes and suggests new hypotheses,
      especially involving occipital association and speech production areas. It also
      suggests finer localization of volume reduction in the hippocampus and other
      limbic structures and in the frontal lobe. Pattern classification showed high
      sensitivity and specificity for the diagnosis of schizophrenia, suggesting the
      potential utility of magnetic resonance imaging as a diagnostic aid.

PMID- 16275810
TI  - Functional neuroanatomical substrates of altered reward processing in major
      depressive disorder revealed by a dopaminergic probe.
AB  - CONTEXT: The pathophysiology of major depressive disorder (MDD) includes
      disturbances in several neuroanatomical substrates and neurotransmitter systems.
      The challenge is to elucidate the brain mechanisms of MDD behavioral symptoms,
      chiefly those of anhedonia. OBJECTIVES: To visualize the neuroanatomical
      substrates implicated in altered reward processing in MDD, using functional
      magnetic resonance imaging in combination with a dopaminergic probe (a 30-mg dose
      of oral dextroamphetamine sulfate) to stimulate the brain reward system; and to
      test the hypothesis that a hypersensitive response to dextroamphetamine in MDD
      involves the prefrontal cortex and the striatum. DESIGN AND INTERVENTIONS: Among
      subjects with MDD and healthy control subjects, functional magnetic resonance
      imaging data were collected before and after single-blind administration of
      dextroamphetamine. SETTING: Subjects were recruited through local newspaper
      advertisements and by word of mouth. PARTICIPANTS: Twelve depressed subjects
      (mean age, 34.83 years; male-female ratio, 6:6) met criteria for MDD according to
      the DSM-IV, were not taking antidepressants, and had no comorbid Axis I
      disorders. Twelve control subjects (mean age, 29.33 years; male-female ratio,
      5:7) were healthy volunteers without a history of Axis I disorders. MAIN OUTCOME
      MEASURES: Functional magnetic resonance imaging blood oxygen level-dependent
      activation was measured during a controlled task, and dextroamphetamine-induced
      subjective effects were assessed using the Addiction Research Center Inventory.
      RESULTS: Subjects with MDD had a hypersensitive response to the rewarding effects
      of dextroamphetamine (2-fold increase; t(21) = 2.74, P = .01), with altered brain
      activation in the ventrolateral prefrontal cortex and the orbitofrontal cortex
      and the caudate and putamen (F(1,44) = 11.93, P = .001). CONCLUSION: Dopamine
      related neuroanatomical substrates are involved in altered reward processing in
      MDD, shedding light on the neurobiology of the anhedonic symptoms in MDD and
      suggesting these substrates as future therapeutic targets.

PMID- 16275811
TI  - Cost-effectiveness of an intervention to prevent depression in at-risk teens.
AB  - CONTACT: Depression is common in adolescent offspring of depressed parents and
      can be prevented, but adoption of prevention programs is dependent on the balance
      of their incremental costs and benefits. OBJECTIVE: To examine the incremental
      cost-effectiveness of a group cognitive behavioral intervention to prevent
      depression in adolescent offspring of depressed parents. DESIGN: Cost
      effectiveness analysis of a recent randomized controlled trial. SETTING: Kaiser
      Permanente Northwest, a large health maintenance organization. PARTICIPANTS:
      Teens 13 to 18 years old at risk for depression. INTERVENTIONS: Usual care (n =
      49) or usual care plus a 15-session group cognitive therapy prevention program (n
      = 45). MAIN OUTCOME MEASURES: Clinical outcomes were converted to depression-free
      days and quality-adjusted life-years. Total health maintenance organization
      costs, costs of services received in other sectors, and family costs were
      combined with clinical outcomes in a cost-effectiveness analysis comparing the
      intervention with usual care for 1 year after the intervention. RESULTS: Average
      cost of the intervention was $1632, and total direct and indirect costs increased
      by $610 in the intervention group. However, the result was not statistically
      significant, suggesting a possible cost offset. Estimated incremental cost per
      depression-free day in the base-case analysis was $10 (95% confidence interval, 
      $13 to $52) or $9275 per quality-adjusted life-year (95% confidence interval, 
      $12 148 to $45 641). CONCLUSIONS: Societal cost-effectiveness of a brief
      prevention program to reduce the risk of depression in offspring of depressed
      parents is comparable to that of accepted depression treatments, and the program
      is cost-effective compared with other health interventions commonly covered in
      insurance contracts.

PMID- 16275812
TI  - Anxiety disorders and risk for suicidal ideation and suicide attempts: a
      population-based longitudinal study of adults.
AB  - CONTEXT: Controversy exists whether anxiety disorders are independently
      associated (ie, after adjusting for comorbid mental disorders) with suicidal
      ideation and suicide attempts. OBJECTIVE: To examine whether anxiety disorders
      are risk factors for suicidal ideation and suicide attempts in a large population
      based longitudinal study. METHODS: Data come from the Netherlands Mental Health
      Survey and Incidence Study, a prospective population-based survey with a baseline
      and 2 follow-up assessments over a 3-year period. The Composite International
      Diagnostic Interview was used to assess DSM-III-R mental disorders. Lifetime
      diagnoses of anxiety disorders (social phobia, simple phobia, generalized anxiety
      disorder, panic disorder, agoraphobia, obsessive-compulsive disorder) were
      assessed at baseline. Multiple logistic regression analyses were used to examine
      whether anxiety disorders were associated with suicidal ideation and attempts at
      baseline (n = 7076) and whether anxiety disorders were risk factors for
      subsequent onset of suicidal ideation and attempts (n = 4796). RESULTS: After
      adjusting for sociodemographic factors and all other mental disorders assessed in
      the survey, baseline presence of any anxiety disorder was significantly
      associated with suicidal ideation and suicide attempts in both the cross
      sectional analysis (adjusted odds ratio for suicidal ideation, 2.29; 95%
      confidence interval, 1.85-2.82; adjusted odds ratio for suicidal attempts, 2.48;
      95% confidence interval, 1.70-3.62) and longitudinal analysis (adjusted odds
      ratio for suicidal ideation, 2.32; 95% confidence interval, 1.31-4.11; adjusted
      odds ratio for suicide attempts, 3.64; 95% confidence interval, 1.70-7.83).
      Further analyses demonstrated that the presence of any anxiety disorder in
      combination with a mood disorder was associated with a higher likelihood of
      suicide attempts in comparison with a mood disorder alone. CONCLUSIONS: This is
      the first study to demonstrate that a preexisting anxiety disorder is an
      independent risk factor for subsequent onset of suicidal ideation and attempts.
      Moreover, the data clearly demonstrate that comorbid anxiety disorders amplify
      the risk of suicide attempts in persons with mood disorders. Clinicians and
      policymakers need to be aware of these findings, and further research is required
      to delineate whether treatment of anxiety disorders reduces the risk of
      subsequent suicidal behavior.

PMID- 16275813
TI  - A twin registry study of the relationship between posttraumatic stress disorder
      and nicotine dependence in men.
AB  - CONTEXT: Recent studies indicate a strong association between posttraumatic
      stress disorder (PTSD) and nicotine dependence (ND). However, the explanation for
      the association remains unclear. OBJECTIVE: To test competing explanations for
      the association between PTSD and ND. DESIGN, SETTING, AND PARTICIPANTS: Analysis
      of data on 6744 members of the Vietnam Era Twin Registry, a national registry of
      all male-male twin pairs who served in the military during the Vietnam era
      interviewed in 1991-1992. MAIN OUTCOME MEASURES: Risk of PTSD and ND using the
      Diagnostic Interview Schedule for the DSM-III-R. RESULTS: The prevalence of ND
      was elevated among trauma-exposed individuals (52.0%) and those with PTSD (71.7%)
      compared with unexposed individuals (40.5%). This association was significant for
      ND and for trauma without PTSD (odds ratio, 1.31; 95% confidence interval [CI],
      1.18-1.45) and for PTSD (odds ratio, 2.34; 95% CI, 1.92-2.84) and was not
      entirely explained by shared risk factors. Shared genetic effects explained 63%
      of the PTSD-ND association; the remaining covariance was explained by individual
      specific environmental effects. Using survival analysis with time-dependent
      covariates, ND was associated with a substantially increased risk of PTSD among
      trauma-exposed men (hazard ratio, 1.98; 95% CI, 1.61-2.42). Trauma (hazard ratio,
      1.49; 95% CI, 1.35-1.64) and PTSD (hazard ratio, 1.36; 95% CI, 1.14-1.61) were
      less strongly but significantly associated with increased risk of ND onset after
      controlling for shared risk factors. CONCLUSIONS: Most of the PTSD-ND association
      is explained by shared genetic effects. However, there is a substantial, robust
      PTSD-ND association not explained by shared risk factors. Multiple explanations
      for the association were supported; however, the strongest association was
      consistent with preexisting ND increasing the risk of PTSD onset. These data
      suggest that male veterans with a history of ND may be at increased risk for
      PTSD. Further research on the biological mechanisms underlying PTSD-ND
      comorbidity is needed.

PMID- 16275814
TI  - Randomized, controlled, crossover trial of methylphenidate in pervasive
      developmental disorders with hyperactivity.
AB  - CONTEXT: Hyperactivity and inattention are common symptoms in children with
      autistic disorder and related pervasive developmental disorders, but studies of
      stimulants in these conditions have been inconclusive. OBJECTIVES: To determine
      the efficacy and safety of methylphenidate hydrochloride in children with
      pervasive developmental disorders and hyperactivity. DESIGN: Double-blind,
      placebo-controlled, crossover trial followed by open-label continuation. SETTING:
      Five academic outpatient clinics. PARTICIPANTS: Seventy-two drug-free children,
      aged 5 to 14 years, with pervasive developmental disorders accompanied by
      moderate to severe hyperactivity. INTERVENTIONS: Prior to randomization, subjects
      entered a 1-week test-dose phase in which each subject received placebo for 1 day
      followed by increasing doses of methylphenidate (low, medium, and high doses)
      that were each given for 2 days. The low, medium, and high doses of
      methylphenidate hydrochloride were based on weight, and they ranged from 7.5 mg/d
      to 50.0 mg/d in divided doses. Subjects who tolerated the test dose (n = 66) were
      assigned to receive placebo for 1 week and then 3 methylphenidate doses in random
      order during a double-blind, crossover phase. Children responding to
      methylphenidate then entered 8 weeks of open-label treatment at the individually
      determined best dose. MAIN OUTCOME MEASURES: The primary outcome measure was the
      teacher-rated hyperactivity subscale of the Aberrant Behavior Checklist. Response
      was defined as "much improved" or "very much improved" on the Clinical Global
      Impressions Improvement item coupled with considerable reductions in the parent
      rated and/or teacher-rated Aberrant Behavior Checklist hyperactivity subscale
      score. RESULTS: Methylphenidate was superior to placebo on the primary outcome
      measure, with effect sizes ranging from 0.20 to 0.54 depending on dose and rater.
      Thirty-five (49%) of 72 enrolled subjects were classified as methylphenidate
      responders. Adverse effects led to the discontinuation of study medication in 13
      (18%) of 72 subjects. CONCLUSIONS: Methylphenidate was often efficacious in
      treating hyperactivity associated with pervasive developmental disorders, but the
      magnitude of response was less than that seen in typically developing children
      with attention-deficit/hyperactivity disorder. Adverse effects were more
      frequent.

PMID- 16275815
TI  - Catechol O-methyltransferase gene variant and birth weight predict early-onset
      antisocial behavior in children with attention-deficit/hyperactivity disorder.
AB  - CONTEXT: Early-onset antisocial behavior accompanied by attention
      deficit/hyperactivity disorder is a clinically severe variant of antisocial
      behavior that is associated with a particularly poor outcome. Identifying early
      predictors is thus important. Genetic and prenatal environmental risk factors and
      prefrontal cortical function are thought to contribute. Recent evidence suggests
      that prefrontal cortical function is influenced by a valine/methionine variant in
      the catechol O-methyltransferase (COMT) gene. OBJECTIVE: To test the a priori
      hypothesis that this genetic variant predicts early-onset antisocial behavior in
      a high-risk sample and further examine the effects of birth weight, an
      environmentally influenced index of prenatal adversity previously linked to
      childhood disruptive behaviors and genotype x birth weight interaction. DESIGN,
      SETTING, AND PARTICIPANTS: A family-based genetic study was undertaken between
      1997 and 2003. Participants were prospectively recruited from child and
      adolescent psychiatry and child health clinics in the United Kingdom and included
      240 clinic children who met diagnostic criteria for attention
      deficit/hyperactivity disorder or hyperkinetic disorder. Participants underwent
      comprehensive standardized assessments including measures of antisocial behavior
      and IQ. Main Outcome Measure DSM-IV symptoms of childhood-onset conduct disorder
      rated by trained interviewers using a standard diagnostic interview. RESULTS: The
      results show main effects of the COMT gene variant (P = .002), birth weight (P =
      .002), and a significant gene x environment (COMT x birth weight) interaction (P
      = .006). CONCLUSIONS: Early-onset antisocial behavior in a high-risk clinical
      group is predicted by a specific COMT gene variant previously linked with
      prefrontal cortical function and birth weight, and those possessing the val/val
      genotype are more susceptible to the adverse effects of prenatal risk as indexed
      by lower birth weight.

PMID- 16275816
TI  - Symmetric basal ganglia calcification in a 9-year-old child with MELAS.

PMID- 16275817
TI  - X-linked oligophrenic vermian dysgenesis: syndromic vs non-syndromic X-linked
      mental retardation?

PMID- 16275818
TI  - The trials and tribulations of pediatric drug trials.

PMID- 16275819
TI  - A way out of the maze: Campylobacter jejuni gene polymorphisms define Guillain
      Barre syndrome.

PMID- 16275820
TI  - Challenges and opportunities in clinical trials for spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is the most common fatal neuromuscular disease of
      infancy. SMA type I is the most severe and mortality is usually due to
      respiratory failure. In type II the disability is of later onset and less severe,
      and prognosis has improved primarily due to supportive care. Type III is the
      mildest form with onset usually of weakness in adolescence or young adulthood.
      SMA is an autosomal recessive disorder with deletions or mutations of the gene at
      the 5 q11 locus. There is no specific prevention or treatment, but current
      progress toward potential therapies has been substantial and several candidates
      including histone deacetylase (HDAC) inhibitors are under consideration for
      further evaluation. The authors sought to address the challenges and
      opportunities for testing new therapies for SMA.

PMID- 16275821
TI  - Effect of antiepileptic medication on bone mineral measures.
AB  - OBJECTIVE: Long-term antiepileptic drug (AED) use has been associated with bone
      disease, but many previous studies have been limited by inadequate control
      subjects. We used a cotwin affected sib-pair model to investigate this issue.
      METHODS: The authors studied 31 female twin (15 monozygous and 16 dizygous) and
      four sibling pairs (< 3 years age difference) aged 21 to 75 years, in which one
      member had > 12 months of AED treatment. Areal bone mineral density (ABMD, g/cm2)
      was measured at the lumbar spine (LS), total hip (TH), femoral neck (FN), and
      total forearm (FA). Three primary a priori defined subgroups were analyzed: a)
      use for > 2 years, b) use of enzyme-inducing AEDs, or c) age older than 40 years.
      RESULTS: For all pairs (n = 35), there were no significant within-pair
      differences in any ABMD measure. However, in Subgroup a (n = 27), there was a
      within-pair difference at the FA (0.513 vs 0.534, -3.9%, p = 0.016). In Subgroup
      b (n = 29), there was also a within-pair difference at the FA for AED user vs
      nonuser (0.508 vs 0.529, -3.8%, p = 0.010). In Subgroup c (n = 15), there were
      within-pair differences at the FA (0.492 vs 0.524, -6.1%, p = 0.017) and the LS
      (0.884 vs 0.980, -9.8%, p = 0.036). CONCLUSIONS: Patients using AEDs for > 2
      years, in particular those taking enzyme-inducing AEDs and those older than 40
      years, have significantly lower bone mineral density at clinically relevant
      fracture risk sites.

PMID- 16275823
TI  - Isolated insular infarction eliminates contralateral cold, cold pain, and
      pinprick perception.

PMID- 16275822
TI  - Oxcarbazepine adjunctive therapy in infants and young children with partial
      seizures.
AB  - OBJECTIVE: To evaluate the efficacy, safety, and pharmacokinetics of
      oxcarbazepine as adjunctive therapy in infants and young children (1 month to < 4
      years). METHODS: Children 1 month to < 4 years of age with inadequately
      controlled partial seizures taking up to two concomitant antiepileptic drugs
      (AEDs) were enrolled in this rater-blind, randomized, parallel-group study.
      Patients received either high-dose (60 mg/kg/day) or low-dose (10 mg/kg/day)
      oxcarbazepine as oral suspension. The primary efficacy variable was the absolute
      change in electrographic partial seizures with a behavioral correlate (type 1
      seizure) frequency per 24 hours during the last 72 hours of continuous video-EEG
      monitoring in the treatment phase compared with baseline seizure frequency.
      RESULTS: Of 191 patients screened, 128 were randomized: 64 to both oxcarbazepine
      dose groups. The median absolute change in type 1 seizure frequency per 24 hours
      was more effective for the high-dose group (-2.00) compared with the low-dose
      group (-1.37; p = 0.043). The median percentage reduction in type 1 seizure
      frequency per 24 hours was also greater in the high-dose group (83.33%) than in
      the low-dose group (46.18%; p = 0.047). The most frequent adverse events (> or =
      10%) were somnolence and pyrexia, and most were mild in severity. CONCLUSIONS: In
      this study, high-dose oxcarbazepine was significantly more effective than low
      dose oxcarbazepine in controlling partial seizures in infants and very young
      children.

PMID- 16275824
TI  - Elevated hematocrit is associated with reduced reperfusion and tissue survival in
      acute stroke.
AB  - BACKGROUND: Elevated hematocrit (Hct) contributes to blood viscosity and has an
      adverse effect in acute stroke. The authors investigated the influence of Hct on
      tissue fate using serial MRI in acute stroke patients. METHODS: The effects of
      Hct on reperfusion, penumbral salvage, and infarct expansion in 64 patients
      presenting within 24 hours of stroke onset were measured. MRI was performed at
      baseline (< 24 hours), days 3 to 5, and 90 days from stroke onset. RESULTS:
      Median Hct was 42% with a bimodal distribution. There was a strong inverse
      relationship between Hct and reperfusion (Spearman rho = -0.74, p < 0.0001). The
      odds of major reperfusion (> 50% resolution of the baseline perfusion-weighted
      imaging deficit) were significantly lower with increasing Hct (odds ratio [OR] =
      0.53; 95% CI = 0.97 to 1.00), independent of age, perfusion, and diffusion lesion
      volumes and recombinant tissue plasminogen activator (rtPA) administration. There
      was a trend toward reduced penumbral salvage at days 3 to 5 with increasing Hct
      (p = 0.06, 95% CI = -4.76 to 0.14). An increasing Hct was a significant predictor
      of infarct growth (OR = 1.26, 95% CI = 1.00 to 1.59), independent of baseline
      perfusion and diffusion volumes and glucose. The effect of Hct on reperfusion and
      infarct expansion was similar irrespective of rtPA administration (p = 0.31) and
      independent of smoking status. CONCLUSIONS: Higher hematocrit (Hct) values have a
      significant independent association with reduced reperfusion and greater infarct
      size after ischemic stroke. An elevated Hct may also be a potential physiologic
      determinant of reduced penumbral salvage.

PMID- 16275825
TI  - Statins and cognitive function in the elderly: the Cardiovascular Health Study.
AB  - OBJECTIVE: To examine the association of statin drug use on cognitive and MRI
      change in older adults. METHODS: Participants in the Cardiovascular Health Study,
      a longitudinal study of people age 65 or older, were classified into three groups
      determined by whether they were taking statin drugs on a continuous basis,
      intermittently, or not at all. The untreated group was further divided into
      categories based on National Cholesterol Education Program recommendations for
      lipid-lowering treatment. Participants with prevalent or incident clinical TIA or
      stroke or with baseline Modified Mini-Mental State Examination (3MS) scores at or
      below 80 were excluded. Outcomes examined included rate of change on the 3MS over
      an average observational period of 7 years, along with changes in MRI white
      matter grade and measures of atrophy. RESULTS: Three thousand three hundred
      thirty-four participants had adequate data for analysis. At baseline, the
      untreated group in which lipid-lowering drug treatment was recommended were
      slightly older, less likely to be on estrogen replacement, and had higher serum
      cholesterol and lower 3MS scores than the statin-treated group. The rate of
      decline on the 3MS was 0.48 point/year less in those taking statins compared with
      the untreated group for which treatment was recommended (p = 0.069) and 0.49
      point/year less in statin users compared with the group in which lipid-lowering
      treatment was not recommended (p = 0.009). This effect remained after controlling
      for serum cholesterol levels. One thousand seven hundred thirty participants with
      baseline 3MS scores of > 80 underwent cranial MRI scans on two occasions
      separated by 5 years. There was no significant difference in white matter grade
      change or atrophy measures between groups. CONCLUSION: Statin drug use was
      associated with a slight reduction in cognitive decline in an elderly population.
      This relationship could not be completely explained by the effect of statins on
      lowering of serum cholesterol.

PMID- 16275826
TI  - What do people at risk for Alzheimer disease think about surrogate consent for
      research?
AB  - BACKGROUND: Research involving decisionally incapable adults remains an unsettled
      and controversial policy issue, especially for protocols that involve significant
      risk to participants. Few data exist to guide policymakers and IRBs OBJECTIVE:
      Survey the views of persons at heightened risk for dementia regarding the
      acceptability of surrogate consent for biomedical research of varying levels of
      risks and potential benefits. METHODS: Using a mail survey, the authors surveyed
      the participants at one of the sites of the Alzheimer's Disease Anti-inflammatory
      Prevention Trial (all participants are 70 years old or older with at least one
      first-degree relative with dementia) and measured responses regarding the
      acceptability of surrogate consent for 10 research scenarios of varying degrees
      of risks and benefits (ranging from an observation study to a gene transfer
      protocol), given from the perspectives of social policy, personal preferences for
      self, and preferences when deciding on behalf of a loved one. RESULTS: Two
      hundred twenty-nine of 259 eligible participants responded (88%). A large
      majority (>90%) found minimal risk studies as well as randomized clinical trials
      of new medications acceptable for surrogate consent. A smaller majority found the
      more invasive studies acceptable. Participants were more cautious when deciding
      for a loved one. General attitude toward biomedical research and scenario
      specific risk perception were strong independent predictors. Demographic and
      personal history variables had relatively little effect. CONCLUSIONS: Laypersons
      at heightened risk of Alzheimer disease discriminate among research scenarios of
      varying risks and burdens. They are supportive of surrogate consent-based
      research even when the risks and burdens are significant to the subjects; these
      opinions appear to be based in part on their assessment of risks as well as on
      their general attitude toward biomedical research.

PMID- 16275827
TI  - Association of homocysteine with plasma amyloid beta protein in aging and
      neurodegenerative disease.
AB  - BACKGROUND: Elevated plasma total homocysteine (tHcy) is a risk factor for
      cardiovascular disease and is reported to be an independent risk factor for
      Alzheimer disease (AD) and cognitive decline. tHcy may potentiate neurotoxic and
      vasculopathic processes, including amyloid beta protein (Abeta) metabolism,
      implicated in neurodegenerative diseases. OBJECTIVE: To examine the relationship
      of plasma total tHcy levels with clinical, demographic, biochemical, and genetic
      factors in aging, mild cognitive impairment (MCI), AD, cerebral amyloid
      angiopathy (CAA), and Parkinson disease (PD). METHODS: Plasma tHcy, folate,
      vitamin B(12), creatinine, and Abeta levels were assessed in individuals
      evaluated in the Memory, Stroke, and Movement Disorders Units of Massachusetts
      General Hospital with diagnoses of AD (n = 145), MCI (n = 47), PD (n = 93), CAA
      (67), hypertensive intracerebral hemorrhage (hICH) (n = 25), and no dementia (n =
      88). RESULTS: The tHcy levels did not differ across AD, MCI, CAA, hICH, and
      nondemented control subjects but were increased in the PD group (p < 0.01). The
      elevated levels within the PD group were due to high tHcy in individuals taking
      levodopa (p < 0.0001). Increasing tHcy was associated with worse cognition in the
      PD cases, but not the other diagnostic groups. tHcy levels positively correlated
      with plasma Abeta levels even after adjustments for age and creatinine (p <
      0.0001). CONCLUSIONS: Mean tHcy levels increased with age but did not
      discriminate diagnostic groups aside from significant elevation in patients with
      PD taking levodopa. The positive association between tHcy and plasma Abeta levels
      raises the possibility that these circulating factors could interact to affect AD
      risk and cognition in PD.

PMID- 16275828
TI  - Carotid dissection causing occipital lobe infarction.

PMID- 16275829
TI  - Benefits of fatty fish on dementia risk are stronger for those without APOE
      epsilon4.
AB  - OBJECTIVE: To compare associations of lean fish vs fatty fish (tuna or other
      fish) intake with dementia, Alzheimer disease (AD), and vascular dementia (VaD)
      and in relation to APOE epsilon4 status in the Cardiovascular Health Cognition
      Study (CHCS). METHODS: Fish intake was assessed by food frequency questionnaires.
      Incident dementia, AD, and VaD were determined through a series of cognitive
      tests, physician's assessment, and committee consensus. We used Cox proportional
      hazards regression to calculate hazard ratios of dementia, AD, and VaD with lean
      fried fish, fatty fish, or total fish intake, which were then stratified by the
      presence of APOE epsilon4. RESULTS: Although consumption of lean fried fish had
      no protective effect, consumption of fatty fish more than twice per week was
      associated with a reduction in risk of dementia by 28% (95% CI: 0.51 to 1.02),
      and AD by 41% (95% CI: 0.36 to 0.95) in comparison to those who ate fish less
      than once per month. Stratification by APOE epsilon4 showed this effect to be
      selective to those without the epsilon4 allele. Adjustment by education and
      income attenuated the effect. CONCLUSION: In the Cardiovascular Health Cognition
      Study, consumption of fatty fish was associated with a reduced risk of dementia
      and Alzheimer disease for those without the APOE epsilon4 allele.

PMID- 16275830
TI  - Can allodynic migraine patients be identified interictally using a questionnaire?
AB  - OBJECTIVE: The gradual development of cutaneous allodynia during the course of a
      migraine attack is commonly detected by quantitative sensory testing (QST) in
      migraineurs seeking secondary and tertiary medical help. In this study, the
      authors developed a questionnaire that tested the recollection of the patients on
      their skin sensitivity during past migraine attacks. METHODS: The authors devised
      a series of questions regarding skin sensitivity during migraine and posed them
      to 89 migraineurs when they were free of migraine (Visit 1). To validate their
      recollections, the authors determined the patients' pain thresholds to mechanical
      and thermal skin stimuli in the absence of migraine (Visit 1) and during an
      attack (Visit 2), using QST. RESULTS: Whereas 75.3% of the patients testified to
      at least one type of skin hypersensitivity during migraine, 24.7% were unaware of
      any abnormal skin sensitivity. The questionnaire correctly identified 84.8% of
      the 66 patients classified as allodynic by QST and mislabeled the remaining 15.2%
      as nonallodynic (false negatives). Among the 23 patients classified as
      nonallodynic by QST, 47.8% were mislabeled as allodynic using the questionnaire
      (false positives). Among the total number of 89 patients studied, the
      questionnaire produced 62.9% true positives and 13.5% true negatives (= 76.4%
      correct labeling) vs 12.4% false positives and 11.2% false negatives (= 23.6%
      mislabeling). CONCLUSION: The reliability of the questionnaire as a diagnostic
      tool of allodynia varies with the proportion of allodynic patients in a given
      clinic. The major source of variability is the misconception of nonallodynic
      patients that their skin is hypersensitive during migraine.

PMID- 16275831
TI  - Comparison of botulinum toxin serotypes A and B for the treatment of cervical
      dystonia.
AB  - OBJECTIVE: To directly compare two serotypes of botulinum toxin (BoNTA and BoNTB)
      in cervical dystonia (CD) using a randomized, double-blind, parallel-arm study
      design. METHODS: Subjects with CD who had a previous response from BoNTA were
      randomly assigned to BoNTA or BoNTB and evaluated in a blinded fashion at
      baseline, 4 weeks, 8 weeks, and 2-week intervals thereafter until loss of 80% of
      clinical effect or completion of 20 weeks of observation. CD severity was
      measured with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS),
      and adverse events were assessed by structured interview. Statistical analysis
      included Wilcoxon rank sum test, log rank tests, and Kaplan-Meier survival curves
      for duration of effect. RESULTS: A total of 139 subjects (BoNTA, n = 74; BoNTB, n
      = 65) were randomized at 19 study sites. Improvement in TWSTRS score was found at
      4 weeks after injection and did not differ between serotypes. Dysphagia and dry
      mouth were more frequent with BoNTB (dysphagia: BoNTA 19% vs BoNTB 48%, p =
      0.0005; dry mouth (BoNTA 41% vs BoNTB 80%, p < 0.0001). In clinical responders,
      BoNT A had a modestly longer duration of benefit (BoNTA 14 weeks, BoNTB 12.1
      weeks, p = 0.033). CONCLUSION: Both serotypes of botulinum toxin (BoNTA and
      BoNTB) had equivalent benefit in subjects with cervical dystonia at 4 weeks.
      BoNTA had fewer adverse events and a marginally longer duration of effect in
      subjects showing a clinical response.

PMID- 16275832
TI  - Progression of motor impairment and disability in Parkinson disease: a population
      based study.
AB  - OBJECTIVE: To investigate risk factors and the rate of progression of motor
      symptoms and disability in a population-based cohort of patients with Parkinson
      disease (PD). METHODS: In all, 232 patients with PD, derived from a community
      based prevalence study, were followed prospectively over an 8-year period. Follow
      up examinations were done 4 and 8 years after baseline, and 144 patients
      participated in at least one follow-up examination. Information on motor function
      and disability was obtained using the Unified Parkinson Disease Rating Scale
      (UPDRS), the Hoehn and Yahr staging, and the Schwab and England score. Population
      averaged logistic regression models were used to describe annual disease
      progression and to analyze the influence of potential risk factors on functional
      decline. RESULTS: We found a similar mean annual decline in the UPDRS motor score
      and the Hoehn and Yahr staging of 3.1% and 3.2%, respectively. Also the UPDRS
      Activity of Daily Living (ADL) score and the Schwab and England scale changed
      similarly, with 3.5% and 3.6% per year, respectively. Age, age at onset, disease
      duration, and excessive daytime somnolence at baseline were strong and
      independent predictors of greater impairment in motor function and disability.
      Cognitive impairment at baseline predicted higher disability and higher Hoehn and
      Yahr scores. Time by age-at-onset interactions were found for the UPDRS motor
      score and the Hoehn and Yahr staging. CONCLUSIONS: Motor function and disability
      worsened significantly with time, and to a similar extent. Age, age at onset and
      disease duration, as well as symptoms thought to be due to involvement of non
      dopaminergic brain structures, are predictors of more impaired motor function and
      disability. However, age at disease onset was the main predictor of motor decline
      in our cohort, indicating a slower and more restricted pathologic disease process
      in patients with young-onset PD.

PMID- 16275833
TI  - Excessive daytime sleepiness and subsequent development of Parkinson disease.
AB  - OBJECTIVE: To determine if excessive daytime sleepiness (EDS) can predate future
      Parkinson disease (PD). METHODS: EDS was assessed in 3,078 men aged 71 to 93
      years in the Honolulu-Asia Aging Study from 1991 to 1993. All were free of
      prevalent PD and dementia. Follow-up for incident PD was based on three repeat
      neurologic assessments from 1994 to 2001. RESULTS: During the course of follow
      up, 43 men developed PD (19.9/10,000 person-years). After age adjustment, there
      was more than a threefold excess in the risk of PD in men with EDS vs men without
      EDS (55.3 vs 17.0/10,000 person-years; odds ratio [OR] = 3.3; 95% CI = 1.4 to
      7.0; p = 0.004). Additional adjustment for insomnia, cognitive function,
      depressed mood, midlife cigarette smoking and coffee drinking, and other factors
      failed to alter the association between EDS and PD (OR = 2.8; 95% CI = 1.1 to
      6.4; p = 0.014). Other sleep related features such as insomnia, daytime napping,
      early morning grogginess, and frequent nocturnal awakening showed little relation
      with the risk of PD. CONCLUSIONS: Excessive daytime sleepiness may be associated
      with an increased risk of developing Parkinson disease.

PMID- 16275835
TI  - Leao's cortical spreading depression: from experimental "artifact" to
      physiological principle.
AB  - Cortical spreading depression was described in 1943 by Aristides Leao, a
      Brazilian neurophysiologist. Initially considered to be a mysterious event as it
      was discovered serendipitously, its nature has become progressively better known.
      Cortical spreading depression is now accepted as the mechanism underlying
      migraine aura and has became known as either Leao's spreading depression or
      cortical spreading depression. Recent studies have suggested a role for Leao's
      cortical spreading depression in the pathogenesis and symptomatology of
      neurologic disorders such as transient global amnesia, head injury, and
      cerebrovascular diseases.

PMID- 16275834
TI  - Predicting gadolinium enhancement status in MS patients eligible for randomized
      clinical trials.
AB  - BACKGROUND: Gadolinium enhancement is often used in randomized clinical trials to
      evaluate the efficacy of new drugs in multiple sclerosis (MS). Knowledge about
      predictors of enhancement status is important for the selection of patients for
      MRI monitored trials. METHODS: Data from 17 trials were available in anonymized
      format through the Sylvia Lawry Centre for MS Research. In an open part
      containing 1,328 (non primary progressive) patients, two logistic regression
      analyses were explored, including demographic, clinical, and MRI predictors. The
      authors examined the area under the curve (AUC) and the increase in positive
      predictive value (PPV). The final selection of models was validated in a closed
      part of 848 comparable patients. RESULTS: Age at onset, disease duration, and
      disease course (CIS/RR/SP) were important predictors from the multivariate
      models. Further, a multivariate model including T2 burden of disease was more
      predictive than one with only clinical predictors (AUC 0.719 vs 0.625, p <
      0.001). For the model with T2 burden of disease, the PPV was 66.8%, compared to
      58.5% for the model without (a priori chance 46.4%). These findings were
      unequivocally confirmed in the closed part of the database. CONCLUSION:
      Gadolinium status can be predicted by a set of baseline variables, certainly when
      T2 burden of disease is included. These findings may benefit the design and
      statistical power of future randomized clinical trials.

PMID- 16275836
TI  - Eye movement abnormalities in stiff person syndrome.
AB  - The authors describe a 38-year-old woman with stiff person syndrome (SPS) and
      gaze-holding nystagmus, limited abduction, vertical and horizontal ocular
      misalignment, deficient smooth pursuit, and impaired saccade initiation. There
      was no evidence of ocular myasthenia, indicating that abnormalities of ocular
      motor function can occur as a primary manifestation of SPS, perhaps from
      depletion of GABA.

PMID- 16275837
TI  - Stiff child syndrome with mutation of DYT1 gene.
AB  - The authors report a Chinese boy with a DYT1 gene mutation having muscle
      stiffness, severe painful muscle spasm, myoclonus, and dystonia compatible with
      stiff child syndrome. Autoantibodies to glutamic acid decarboxylase (anti-GAD)
      were absent. His asymptomatic mother had a DYT1 mutation. His asymptomatic sister
      has diabetes mellitus and antibodies to glutamic acid decarboxylase but no DYT1
      mutation.

PMID- 16275838
TI  - Ventrolateral medullary compression in hypertensive patients with hemifacial
      spasm.
AB  - In a patient-controlled study, the authors demonstrated a significantly higher
      prevalence of rostral ventrolateral medulla (VLM) compression in hypertensive
      patients with hemifacial spasm (HFS) compared with age-, sex-, race-, disease
      duration-, and disease severity-matched normotensive patients with HFS (p =
      0.02). Hypertensive HFS patients were more likely to have a greater severity of
      neurovascular compression at the VLM compared with normotensive HFS patients (p =
      0.008). VLM compression is associated with risk of hypertension in this study
      population.

PMID- 16275839
TI  - Extracranial vertebral and carotid dissection occurring in the course of
      subarachnoid hemorrhage.
AB  - The pathogenesis of both intracranial aneurysms and spontaneous cervical artery
      dissection may be related to an underlying vasculopathy. Seven cases of
      spontaneous cervical artery dissection in the course of ruptured berry aneurysms
      are reported here.

PMID- 16275840
TI  - APOE epsilon2/epsilon4 polymorphism and cerebral microbleeds on gradient-echo
      MRI.
AB  - The association of APOE genotypes with cerebral microbleeds (CMBs) was examined
      on the basis of the location of CMBs in 414 patients who were admitted primarily
      because of stroke. With respect to possession of the epsilon2 or epsilon4 allele,
      the adjusted odds ratio was 1.94 (1.05 to 3.58) for lobar CMBs but 1.21 (0.69 to
      2.11) for nonlobar CMBs. This suggests that the pathogenesis of CMBs may differ
      depending on their location.

PMID- 16275841
TI  - Ictal monoparesis associated with lesions in the primary somatosensory area.
AB  - Reported are three patients with ictal monoparesis of an arm. In the hemisphere
      contralateral to the monoparesis, ictal and interictal epileptiform discharges
      were observed in the centroparietal area, and a well-circumscribed lesion was
      commonly present in the primary arm somatosensory area (SI). In the presence of
      an SI lesion, the epileptic activity at the sensorimotor area could lead to
      selective or predominant activation of the inhibitory motor system.

PMID- 16275842
TI  - Intractable hiccup and nausea with periaqueductal lesions in neuromyelitis
      optica.
AB  - Intractable hiccup and nausea (IHN) was found in eight of 47 cases of relapsing
      neuromyelitis optica (NMO) (17%) but in none of 130 cases of multiple sclerosis
      (MS). IHN resolved with methylprednisolone. In six cases, MRI detected linear
      medullary lesions involving the pericanal region, the area postrema, and the
      nucleus tractus solitarius. Like long and centrally located myelitis, a linear
      medullary lesion causing IHN may distinguish NMO from MS.

PMID- 16275843
TI  - Gray matter decrease in patients with chronic tension type headache.
AB  - Using MRI and voxel-based morphometry, the authors investigated 20 patients with
      chronic tension type headache (CTTH) and 20 patients with medication-overuse
      headache and compared them to 40 controls with no headache history. Only patients
      with CTTH demonstrated a significant gray matter decrease in regions known to be
      involved in pain processing. The finding implies that the alterations are
      specific to CTTH rather than a response to chronic head pain or chronification
      per se.

PMID- 16275844
TI  - Serum anticholinergic activity, white matter hyperintensities, and cognitive
      performance.
AB  - The authors investigated whether the cognitive impairments associated with white
      matter hyperintensities (WMH) in normal elderly subjects are exacerbated by any
      anticholinergic medications being taken by the subjects. Results showed serum
      anticholinergic activity (SAA) and WMH volume to have a synergistic interaction
      such that the cognitive decrements associated with increasing WMH volume were
      greatest in those older individuals in the highest quartile of the SAA
      distribution.

PMID- 16275845
TI  - CSF amyloid beta42 and tau levels correlate with AIDS dementia complex.
AB  - There is concern that AIDS dementia complex (ADC) may be complicated by Alzheimer
      disease (AD). Because AD presence and risk are related to CSF beta-amyloid(1-42)
      (Abeta42), total tau (t-tau), and phosphorylated tau (p-tau), the authors
      examined these in ADC, AD, and controls. ADC had significantly decreased CSF
      Abeta42 and increased t-tau and p-tau concentrations similar to AD, suggesting
      that ADC may be associated with AD or an AD-like process.

PMID- 16275846
TI  - Genomic microarray analysis identifies candidate loci in patients with corpus
      callosum anomalies.
AB  - Absence of the corpus callosum is often associated with cognitive deficits,
      autism, and epilepsy. Using a genomic microarray, the authors analyzed DNA from
      25 patients with radiographically confirmed callosal anomalies and identified
      three patients with de novo copy number changes in chromosome regions 2q37,
      6qter, and 8p. Chromosomal deletions and duplications may be a relatively common
      cause of cerebral malformations.

PMID- 16275847
TI  - Bilateral isolated phrenic neuropathy causing painless bilateral diaphragmatic
      paralysis.
AB  - The authors report four patients with a syndrome of painless bilateral isolated
      phrenic neuropathy. Electrophysiologic testing demonstrated active denervation
      restricted to the diaphragm. Long-term recovery was poor. The authors conclude
      that bilateral isolated phrenic neuropathy is a cause of painless diaphragmatic
      paralysis distinguishable from immune brachial plexus neuropathy and other
      neuromuscular disorders with similar clinical presentation.

PMID- 16275848
TI  - Extensive brain calcification and dementia in postsurgical hypoparathyroidism.

PMID- 16275849
TI  - Phosphorylated tau predicts rate of cognitive decline in MCI subjects: a
      comparative CSF study.

PMID- 16275850
TI  - Concurrent dolichoectasia of basilar and coronary arteries.

PMID- 16275851
TI  - Isolated dropped head due to adult-onset nemaline myopathy treated by posterior
      fusion.

PMID- 16275852
TI  - Long-term 24-hour duodenal infusion of levodopa: outcome and dose requirements.

PMID- 16275853
TI  - Absorption of orally disintegrating carbidopa-levodopa requires intact small
      bowel function.

PMID- 16275854
TI  - Nonresponsiveness to anticholinesterase agents in patients with MuSK-antibody
      positive MG.

PMID- 16275855
TI  - Levodopa addiction in idiopathic Parkinson disease.

PMID- 16275856
TI  - Sustained recovery of progressive multifocal leukoencephalopathy after treatment
      with IL-2.

PMID- 16275858
TI  - Position on stem cell research.

PMID- 16275859
TI  - Risedronate therapy for prevention of hip fracture after stroke in elderly women.

PMID- 16275860
TI  - fMRI evidence of compensatory mechanisms in older adults at genetic risk for
      Alzheimer disease.

PMID- 16275861
TI  - Heads down: flat positioning improves blood flow velocity in acute ischemic
      stroke.

PMID- 16275862
TI  - Noninvasive targeted imaging of matrix metalloproteinase activation in a murine
      model of postinfarction remodeling.
AB  - BACKGROUND: Time-dependent activation of matrix metalloproteinases (MMPs) after
      myocardial infarction (MI) contributes to adverse left ventricular (LV)
      remodeling; however, noninvasive methods to monitor this process serially are
      needed. METHODS AND RESULTS: MMP-targeted radiotracers were developed that
      displayed selective binding kinetics to the active MMP catalytic domain. Initial
      nonimaging studies were performed with a (111)In-labeled MMP-targeted radiotracer
      ((111)In-RP782) and negative control compound ((111)In-RP788) in control mice
      (Ctrl) and in mice 1 week after surgically induced MI. Localization of (111)In
      RP782 was demonstrated within the MI by microautoradiography. A 334+/-44%
      increase (P<0.001 versus Ctrl) in relative retention of (111)In-RP782 was
      confirmed by gamma well counting of myocardium. Subsequent high-resolution dual
      isotope planar and hybrid micro-single-photon emission computed tomography/CT
      imaging studies with an analogous 99mTc-labeled MMP-targeted radiotracer (99mTc
      RP805) and 201Tl demonstrated favorable biodistribution and clearance kinetics of
      99mTc-RP805 for in vivo cardiac imaging, with robust retention 1 to 3 weeks after
      MI in regions of decreased 201Tl perfusion. Gamma well counting yielded a similar
      approximately 300% increase in relative myocardial retention of 99mTc-RP805 in MI
      regions (Ctrl, 102+/-9%; 1 week, 351+/-77%; 2 weeks, 291+/-45%; 3 weeks, 292+/
      41%; P<0.05 versus Ctrl). Myocardial uptake in the MI region was also
      significantly increased approximately 5-fold when expressed as percentage
      injected dose per gram tissue. There was also a significant 2-fold increase in
      myocardial activity in remote regions relative to control mice, suggesting
      activation of MMPs in regions remote from the MI. CONCLUSIONS: This novel
      noninvasive targeted MMP radiotracer imaging approach holds significant
      diagnostic potential for in vivo localization of MMP activation and tracking of
      MMP-mediated post-MI remodeling.

PMID- 16275863
TI  - Optimal timing of intervention in non-ST-segment elevation acute coronary
      syndromes: insights from the CRUSADE (Can Rapid risk stratification of Unstable
      angina patients Suppress ADverse outcomes with Early implementation of the
      ACC/AHA guidelines) Registry.
AB  - BACKGROUND: Recent studies indicate that a routine invasive approach for patients
      with unstable angina (UA) and non-ST-segment elevation myocardial infarction
      (NSTEMI) yields improved outcomes compared with a conservative approach, but the
      optimal timing of this approach remains open to debate. METHODS AND RESULTS: We
      used day of hospital presentation as an instrumental variable to study the impact
      of timing of cardiac catheterization and revascularization therapy on acute
      outcomes (death, reinfarction, stroke, cardiogenic shock, or congestive heart
      failure) among patients with UA and NSTEMI. Between January 2001 and September
      2003, 56,352 patients with UA or NSTEMI were treated at 310 US hospitals
      participating in the CRUSADE national quality improvement initiative. Weekend
      patients were defined as those who presented to the hospital between 5 PM on
      Friday and 7 AM on Sunday. All other patients were classified as weekday. Weekday
      patients were similar to weekend patients in terms of demographics, clinical
      characteristics, and the use of medical therapies in the first 24 hours. Although
      overall rates of cardiac catheterization and revascularization were similar for
      the 2 groups, median time to catheterization was significantly longer for weekend
      than for weekday patients (46.3 versus 23.4 hours, P<0.0001). This delay was not
      associated with increased in-hospital adverse events, including death (weekend
      4.4% versus weekday 4.1%, P=0.23), recurrent MI (2.9% versus 3.0%, P=0.36), or
      their combination (6.6% versus 6.6%, P=0.86). These findings were not affected by
      risk adjustment or use of alternative definitions of weekend versus weekday
      presentation. When weekend presentation was used as the basis for an instrumental
      variable analysis, we found that catheterization within the first 12 hours of
      presentation was associated with a nonsignificant trend toward reduced in
      hospital mortality (absolute risk reduction 1.9%; 95% CI 6.7% lower to 2.9%
      higher; P=0.43) that decreased with longer treatment delays. CONCLUSIONS:
      Although weekend presentation is associated with a delay in invasive management
      among patients with UA and NSTEMI, in the context of contemporary medical
      therapy, this does not increase adverse events. Weekend presentation appears to
      fulfill accepted criteria as an instrumental variable for studying the optimal
      timing of invasive management for acute coronary syndrome patients. Using weekend
      status as an instrumental variable, we found no significant benefit to early
      catheterization, although we could not exclude an important risk reduction,
      particularly for catheterization within 12 hours of presentation.

PMID- 16275864
TI  - Low thyroid function leads to cardiac atrophy with chamber dilatation, impaired
      myocardial blood flow, loss of arterioles, and severe systolic dysfunction.
AB  - BACKGROUND: Although thyroid dysfunction has been linked to heart failure, it is
      not clear whether hypothyroidism alone can cause heart failure. METHODS AND
      RESULTS: Hypothyroidism was induced in adult rats by treatment with 0.025%
      propylthiouracil (PTU) for 6 weeks (PTU-S) and 1 year (PTU-L). Echocardiographic
      measurements, left ventricular (LV) hemodynamics, isolated myocyte length (KOH
      method), myocardial blood flow (fluorescent microspheres), arteriolar
      morphometry, and gene expression (Western blot) were determined. Heart weight,
      heart rate, LV systolic blood pressure, LV ejection fraction, LV fractional
      shortening, and systolic wall thickness were reduced in PTU-S and PTU-L rats. LV
      internal diameter in systole increased by 40% in PTU-S and 86% in PTU-L. LV
      internal dimension in diastole was increased in PTU-S and PTU-L rats, but only
      PTU-L rats showed a significant increase in myocyte length due to series
      sarcomere addition. Resting and maximum (adenosine) myocardial blood flow were
      reduced in both PTU-S and PTU-L rats. Impaired blood flow was due to a large
      reduction in arteriolar length density and small arterioles in PTU-S and PTU-L
      (P<0.05 or greater for all of the above comparisons). Expression of
      sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA)-2a and alpha-myosin heavy
      chain were reduced in hypothyroidism, whereas phospholamban and beta-myosin heavy
      chain were increased. CONCLUSIONS: Hypothyroidism led to severe, progressive
      systolic dysfunction and increased chamber diameter/wall thickness ratio despite
      a reduction in cardiac mass. Chamber dilatation in PTU-L rats was due to series
      sarcomere addition, typical of heart failure. Hypothyroidism resulted in impaired
      myocardial blood flow due to a dramatic loss of arterioles. Thus, we have
      identified 2 important new mechanisms by which low thyroid function may lead to
      heart failure.

PMID- 16275865
TI  - Cardioprotection by intermittent fasting in rats.
AB  - BACKGROUND: Intermittent fasting (IF), a dietary regimen in which food is
      available only every other day, increases the life span and reduces the incidence
      of age-associated diseases in rodents. We have reported neuroprotective effects
      of IF against ischemic injury of the brain. In this study, we examined the
      effects of IF on ischemic injury of the heart in rats. METHODS AND RESULTS: After
      3 months of IF or regular every-day feeding (control) diets started in 2-month
      old rats, myocardial infarction (MI) was induced by coronary artery ligation.
      Twenty-four hours after MI, its size in the IF group was 2-fold smaller, the
      number of apoptotic myocytes in the area at risk was 4-fold less, and the
      inflammatory response was significantly reduced compared with the control diet
      group. Serial echocardiography revealed that during 10 weeks after MI (with
      continuation of the IF regimen), the left ventricular (LV) remodeling and MI
      expansion that were observed in the control diet group were absent in the IF
      group. In a subgroup of animals with similar MI size at 1 week after MI, further
      observation revealed less remodeling, better LV function, and no MI expansion in
      the IF group compared with the control group. CONCLUSIONS: IF protects the heart
      from ischemic injury and attenuates post-MI cardiac remodeling, likely via
      antiapoptotic and antiinflammatory mechanisms.

PMID- 16275866
TI  - Electrophysiological findings during ablation of persistent atrial fibrillation
      with electroanatomic mapping and double Lasso catheter technique.
AB  - BACKGROUND: Pulmonary veins (PVs) can be completely isolated with continuous
      circular lesions (CCLs) around the ipsilateral PVs. However, electrophysiological
      findings have not been described in detail during ablation of persistent atrial
      fibrillation (AF). METHODS AND RESULTS: Forty patients with symptomatic
      persistent AF underwent complete isolation of the right-sided and left-sided
      ipsilateral PVs guided by 3D mapping and double Lasso technique during AF.
      Irrigated ablation was initially performed in the right-sided CCLs and
      subsequently in the left-sided CCLs. After complete isolation of both lateral
      PVs, stable sinus rhythm was achieved after AF termination in 12 patients; AF
      persisted and required cardioversion in 18 patients. In the remaining 10
      patients, AF changed to left macroreentrant atrial tachycardia in 6 and common
      type atrial flutter in 4 patients. All atrial tachycardias were successfully
      terminated during the procedure. Atrial tachyarrhythmias recurred in 15 of 40
      patients at a median of 4 days after the initial ablation. A repeat ablation was
      performed at a median of 35 days after the initial procedure in 14 patients.
      During the repeat study, recovered PV conduction was found in 13 patients and
      successfully abolished by focal ablation of the conduction gap of the previous
      CCLs. After a mean of 8+/-2 months of follow-up, 38 (95%) of the 40 patients were
      free of AF. CONCLUSIONS: In patients with persistent AF, CCLs can result in
      either AF termination or conversion to macroreentrant atrial tachycardia in 55%
      of the patients. In addition, recovered PV conduction after the initial procedure
      is a dominant finding in recurrent atrial tachyarrhythmias and can be
      successfully abolished.

PMID- 16275867
TI  - Continuous aortic flow augmentation: a pilot study of hemodynamic and renal
      responses to a novel percutaneous intervention in decompensated heart failure.
AB  - BACKGROUND: Diminished aortic flow may induce adverse downstream vascular and
      renal signals. Investigations in a heart failure animal model have shown that
      continuous aortic flow augmentation (CAFA) achieves hemodynamic improvement and
      ventricular unloading, which suggests a novel therapeutic approach to patients
      with heart failure exacerbation that is inadequately responsive to medical
      therapy. METHODS AND RESULTS: We studied 24 patients (12 in Europe and 12 in the
      United States) with heart failure exacerbation and persistent hemodynamic
      derangement despite intravenous diuretic and inotropic and/or vasodilator
      treatment. CAFA (mean+/-SD 1.34+/-0.12 L/min) was achieved through percutaneous
      (n=19) or surgical (n=5) insertion of the Cancion system, which consists of
      inflow and outflow cannulas and a magnetically levitated and driven centrifugal
      pump. Hemodynamic improvement was observed within 1 hour. Systemic vascular
      resistance decreased from 1413+/-453 to 1136+/-381 dyne.s.cm(-5) at 72 hours
      (P=0.0008). Pulmonary capillary wedge pressure decreased from 28.5+/-4.9 to
      19.8+/-7.0 mm Hg (P<0.0001), and cardiac index (excluding augmented aortic flow)
      increased from 1.97+/-0.44 to 2.27+/-0.43 L.min(-1).m(-2) (P=0.0013). Serum
      creatinine trended downward during treatment (overall P=0.095). There were 8
      complications during treatment, 7 of which were self-limited. Hemodynamics
      remained improved 24 hours after CAFA discontinuation. CONCLUSIONS: In patients
      with heart failure and persistent hemodynamic derangement despite intravenous
      inotropic and/or vasodilator therapy, CAFA improved hemodynamics, with a
      reduction in serum creatinine. CAFA represents a promising, novel mode of
      treatment for patients who are inadequately responsive to medical therapy. The
      clinical impact of the observed hemodynamic improvement is currently being
      explored in a prospective, randomized, controlled trial.

PMID- 16275868
TI  - Increased alpha2 subunit-associated AMPK activity and PRKAG2 cardiomyopathy.
AB  - BACKGROUND: AMP-activated protein kinase (AMPK) regulatory gamma2 subunit
      (PRKAG2) mutations cause a human cardiomyopathy with cardiac hypertrophy,
      preexcitation, and glycogen deposition. PRKAG2 cardiomyopathy is recapitulated in
      transgenic mice overexpressing mutant PRKAG2 N488I in the heart (TGgamma2N488I).
      AMPK is a heterotrimeric kinase consisting of 1 catalytic (alpha) and 2
      regulatory (beta and gamma) subunits. Two alpha-subunit isoforms, alpha1 and
      alpha2, are expressed in the heart; however, the contribution of AMPK utilization
      of these subunits to PRKAG2 cardiomyopathy is unknown. Mice overexpressing a
      dominant-negative alpha2 subunit of AMPK (TGalpha2DN) provide a tool for
      selectively inhibiting alpha2, but not alpha1, subunit-associated AMPK activity.
      METHODS AND RESULTS: In compound-heterozygous TGgamma2N488I/TGalpha2DN mice, AMPK
      activity associated with alpha2 but not alpha1 was decreased compared with
      TGgamma2N488I. The TGalpha2DN transgene reduced the disease phenotype of
      TGgamma2N488I, partially or completely normalizing the ECG, cardiac function,
      cardiac morphology, and exercise capacity in compound-heterozygous mice.
      TGgamma2N488I hearts had normal resting levels of high-energy phosphates and
      could improve cardiac performance during exercise. Cardiac glycogen content
      decreased in TGgamma2N488I mice after exercise stress, indicating availability of
      the stored glycogen for metabolic utilization. No differences in glycogen
      metabolizing enzymes were observed. CONCLUSIONS: The PRKAG2 N488I mutation causes
      inappropriate AMPK activation, which leads to glycogen accumulation and
      conduction system disease. The accumulated glycogen can serve as an energy
      source, and the animals have contractile reserve during exercise. Because the
      dominant-negative alpha2 subunit attenuates the mutant PRKAG2 phenotype, AMPK
      complexes containing the alpha2 rather than the alpha1 subunit are the primary
      mediators of the effects of PRKAG2 mutations.

PMID- 16275869
TI  - Preservation from left ventricular remodeling by front-integrated
      revascularization and stem cell liberation in evolving acute myocardial
      infarction by use of granulocyte-colony-stimulating factor (FIRSTLINE-AMI).
AB  - BACKGROUND: Considering experimental evidence that stem cells enhance myocardial
      regeneration and granulocyte colony-stimulating factor (G-CSF) mediates
      mobilization of CD34+ mononuclear blood stem cells (MNCCD34+), we tested the
      impact of G-CSF integrated into primary percutaneous coronary intervention (PCI)
      management of acute myocardial infarction in man. METHODS AND RESULTS: Fifty
      consecutive patients with ST-segment elevation myocardial infarction were
      subjected to primary PCI stenting with abciximab and followed up for 6 months;
      89+/-35 minutes after successful PCI, 25 patients were randomly assigned in this
      pilot study (PROBE design) to receive subcutaneous G-CSF at 10 microg/kg body
      weight for 6 days in addition to standard care, including aspirin, clopidogrel,
      an ACE inhibitor, beta-blocking agents, and statins. By use of CellQuest software
      on peripheral blood samples incubated with CD45 and CD34, mobilized MNCCD34+ were
      quantified on a daily basis. With homogeneous demographics and clinical and
      infarct-related characteristics, G-CSF stimulation led to mobilization of
      MNCCD34+ to between 3.17+/-2.93 MNCCD34+/microL at baseline and 64.55+/-37.11
      MNCCD34+/microL on day 6 (P<0.001 versus control); there was no indication of
      leukocytoclastic effects, significant pain, impaired rheology, inflammatory
      reactions, or accelerated restenosis at 6 months. Within 35 days, G-CSF and
      MNCCD34+ liberation led to enhanced resting wall thickening in the infarct zone
      of between 0.29+/-0.22 and 0.99+/-0.32 mm versus 0.49+/-0.29 mm in control
      subjects (P<0.001); under inotropic challenge with dobutamine (10 microg.kg(
      1).min(-1)), wall motion score index showed improvement from 1.66+/-0.23 to
      1.41+/-0.21 (P<0.004 versus control) and to 1.35+/-0.24 after 4 months (P<0.001
      versus control), respectively, coupled with sustained recovery of wall thickening
      to 1.24+/-0.31 mm (P<0.001 versus control) at 4 months. Accordingly, resting wall
      motion score index improved with G-CSF to 1.41+/-0.25 (P<0.001 versus control),
      left ventricular end-diastolic diameter to 55+/-5 mm (P<0.002 versus control),
      and ejection fraction to 54+/-8% (P<0.001 versus control) after 4 months.
      Morphological and functional improvement with G-CSF was corroborated by enhanced
      metabolic activity and 18F-deoxyglucose uptake in the infarct zone (P<0.001
      versus control). CONCLUSIONS: G-CSF and mobilization of MNC(CD34+) after
      reperfusion of infarcted myocardium may offer a pragmatic strategy for
      preservation of myocardium and prevention of remodeling without evidence of
      aggravated restenosis.

PMID- 16275870
TI  - Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes
      mellitus.
AB  - BACKGROUND: The incidence of cardiovascular disease (CVD), coronary heart disease
      (CHD), and type 2 diabetes mellitus (T2DM) has not been well defined in persons
      with the metabolic syndrome (at least 3 of the following: abdominal adiposity,
      low HDL cholesterol, high triglycerides, hypertension, and impaired fasting
      glucose). The objective was to investigate risk for CVD, CHD, and T2DM according
      to metabolic syndrome traits. METHODS AND RESULTS: The study followed a cohort of
      3323 middle-aged adults for the development of new CVD, CHD, and T2DM over an 8
      year period. In persons without CVD or T2DM at baseline, the prevalence of the
      metabolic syndrome (> or =3 of 5 traits) was 26.8% in men and 16.6% in women.
      There were 174 incident cases of CVD, 107 of CHD, and 178 of T2DM. In men, the
      metabolic syndrome age-adjusted relative risk (RR) and 95% CIs were RR=2.88 (95%
      CI 1.99 to 4.16) for CVD, RR=2.54 (95% CI 1.62 to 3.98) for CHD, and RR=6.92 (95%
      CI 4.47 to 10.81) for T2DM. Event rates and RRs were lower in women for CVD
      (RR=2.25, 95% CI 1.31 to 3.88) and CHD (RR=1.54, 95% CI 0.68 to 3.53), but they
      were similar for T2DM (RR=6.90, 95% CI 4.34 to 10.94). Population-attributable
      risk estimates associated with metabolic syndrome for CVD, CHD, and T2DM were
      34%, 29%, and 62% in men and 16%, 8%, 47% in women. CONCLUSIONS: Metabolic
      syndrome is common and is associated with an increased risk for CVD and T2DM in
      both sexes. The metabolic syndrome accounts for up to one third of CVD in men and
      approximately half of new T2DM over 8 years of follow-up.

PMID- 16275873
TI  - Images in cardiovascular medicine. Medical treatment of varicose veins.

PMID- 16275872
TI  - Homocysteine and its effects on in-stent restenosis.

PMID- 16275874
TI  - Images in cardiovascular medicine. Acute type I aortic dissection with
      concomitant pulmonary artery dissection.

PMID- 16275871
TI  - Plasma lipoproteins and apolipoproteins as predictors of cardiovascular risk and
      treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk
      (PROSPER).
AB  - BACKGROUND: Statins are important in vascular disease prevention in the elderly.
      However, the best method of selecting older patients for treatment is uncertain.
      We assessed the role of plasma lipoproteins as predictors of risk and of
      treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk
      (PROSPER). METHOD AND RESULTS: The association of LDLc and HDLc with risk was
      examined in the 5804 70- to 82-year-old subjects of PROSPER. Baseline LDLc showed
      no relation to risk of the primary end point in the placebo group (P=0.27), nor
      did on-treatment LDLc in the pravastatin group (P=0.12). HDLc was inversely
      associated with risk in subjects on placebo (P=0.0019) but not in those on
      pravastatin (P=0.24). Risk reduction on pravastatin treatment was unrelated to
      baseline LDLc (P=0.38) but exhibited a significant interaction with HDLc
      (P=0.012). Subjects in the lowest 2 quintiles of HDLc (<1.15 mmol/L) had a risk
      reduction of 33% (hazard ratio, 0.67; 95% confidence limits, 0.55, 0.81;
      P<0.0001), whereas those with higher HDLc showed no benefit (RR, 1.06; 95%
      confidence limits, 0.88, 1.27; P=0.53). During follow-up, there was no relation
      between achieved level of LDLc or HDLc and risk. However, the change in the
      LDLc/HDLc ratio on statin treatment appeared to account for the effects of
      therapy. CONCLUSIONS: In people >70 years old, HDLc appears to be a key predictor
      of risk and of treatment benefit. Findings in PROSPER suggest that statin therapy
      could usefully be targeted to those with HDLc <1.15 mmol/L or an LDLc/HDLc ratio
      >3.3.

PMID- 16275875
TI  - Images in cardiovascular medicine. Detection of active coronary arterial
      vasculitis using magnetic resonance imaging in Kawasaki disease.

PMID- 16275876
TI  - Letter regarding article by Diwan et al, "Doppler estimation of left ventricular
      filling pressures in patients with mitral valve disease".

PMID- 16275877
TI  - Diastolic dysfunction beyond distensibility: adverse effects of ventricular
      dilatation.

PMID- 16275878
TI  - Heart failure research continues to reveal the flaws in nature's unintelligent
      design.

PMID- 16275879
TI  - More potential for sildenafil than potency.

PMID- 16275880
TI  - Transcriptomic and proteomic patterns of systemic inflammation in on-pump and off
      pump coronary artery bypass grafting.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) using cardiopulmonary bypass
      (CPB) provides controlled operative conditions but induces a whole-body
      inflammatory response capable of initiating devastating morbidity and mortality.
      Although technically more demanding, deliberate avoidance of CPB in off-pump
      surgery attenuates the physiological insult associated with CABG. METHODS AND
      RESULTS: To systematically assess the molecular mechanisms underlying the better
      preserved remote organ function, we studied gene expression patterns in
      leukocytes and plasma proteomic response to on-pump and off-pump CABG. Proteomic
      analysis confirmed (tumor necrosis factor-alpha, interleukin [IL]-6, IL-10) and
      expanded (eg, interferon [IFN]-gamma, granulocyte colony-stimulating factor [G
      CSF], monocyte chemotactic protein-1, macrophage inflammatory protein-1beta) the
      mediators released on CPB, whereas blood leukocyte transcriptomics suggested that
      circulating leukocytes are not primarily responsible for this response.
      Interestingly, release of some cytokines (eg, IL-6, IFN-gamma, G-CSF) was
      observed on off-pump surgery to a similar extent but with delayed kinetics. A
      total of 45 of 4868 transcripts were identified to be significantly altered as a
      result of initiation of CPB. Systematic analysis of transcriptional activation by
      CPB revealed primarily genes involved in inflammation-related cell-cell
      communication (such as L-selectin or intercellular adhesion molecule-2) and
      signaling (such as IL-1, IL-8, or IL-18 receptors and toll-like receptors 4, 5,
      and 6), thus confirming a "primed" phenotype of circulating peripheral blood
      mononuclear cells. CONCLUSIONS: Gene array and multiplex protein analysis, only
      in concert, can illuminate the molecular mechanisms responsible for systemic
      sequelae of CPB and indicate that circulating leukocytes overexpress adhesion and
      signaling factors after contact with CPB, which potentially facilitates their
      trapping, eg, in the lungs and may promote a subsequent tissue-associated
      inflammatory response.

PMID- 16275881
TI  - A noninvasive method for assessing impaired diastolic suction in patients with
      dilated cardiomyopathy.
AB  - BACKGROUND: Diastolic suction is a major determinant of early left ventricular
      filling in animal experiments. However, suction remains incompletely
      characterized in the clinical setting. METHODS AND RESULTS: First, we validated a
      method for measuring the spatio-temporal distributions of diastolic
      intraventricular pressure gradients and differences (DIVPDs) by digital
      processing color Doppler M-mode recordings. In 4 pigs, the error of peak DIVPD
      was 0.0+/-0.2 mm Hg (intraclass correlation coefficient, 0.95) compared with
      micromanometry. Forty patients with dilated cardiomyopathy (DCM) and 20 healthy
      volunteers were studied at baseline and during dobutamine infusion. A positive
      DIVPD (toward the apex) originated during isovolumic relaxation, reaching its
      peak shortly after mitral valve opening. Peak DIVPD was less than half in
      patients with DCM than in control subjects (1.2+/-0.6 versus 2.5+/-0.8 mm Hg,
      P<0.001). Dobutamine increased DIVPD in control subjects by 44% (P<0.001) but
      only by 23% in patients with DCM (P=NS). DIVPDs were the consequence of 2
      opposite forces: a driving force caused by local acceleration, and a reversed
      (opposed to filling) convective force that lowered the total DIVPD by more than
      one third. In turn, local acceleration correlated with E-wave velocity and
      ejection fraction, whereas convective deceleration correlated with E-wave
      velocity and ventriculo:annular disproportion. Convective deceleration was
      highest among patients showing a restrictive filling pattern. CONCLUSIONS:
      Patients with DCM show an abnormally low diastolic suction and a blunted capacity
      to recruit suction with stress. By raising the ventriculo:annular disproportion,
      chamber remodeling proportionally increases convective deceleration and adversely
      affects left ventricular filling. These previously unreported mechanisms of
      diastolic dysfunction can be studied by using Doppler echocardiography.

PMID- 16275882
TI  - Mineralocorticoid receptor antagonism ameliorates left ventricular diastolic
      dysfunction and myocardial fibrosis in mildly symptomatic patients with
      idiopathic dilated cardiomyopathy: a pilot study.
AB  - BACKGROUND: Mineralocorticoid receptor antagonism reduces mortality associated
      with heart failure by mechanisms that remain unclear. The effects of the
      mineralocorticoid receptor antagonist spironolactone on left ventricular (LV)
      function and chamber stiffness associated with myocardial fibrosis were
      investigated in mildly symptomatic patients with idiopathic dilated
      cardiomyopathy (DCM). METHODS AND RESULTS: Twenty-five DCM patients with a New
      York Heart Association functional class of I or II were examined before and after
      treatment with spironolactone for 12 months. LV pressures and volumes were
      measured simultaneously, and LV endomyocardial biopsy specimens were obtained.
      Serum concentrations of the carboxyl-terminal propeptide (PIP) and carboxyl
      terminal telopeptide (CITP) of collagen type I were measured. The patients were
      divided into 2 groups on the basis of the serum PIP/CITP ratio (< or =35, group
      A, n=12; >35, group B, n=13), an index of myocardial collagen accumulation. LV
      diastolic chamber stiffness, the collagen volume fraction, and abundance of
      collagen type I and III mRNAs in biopsy tissue were greater and the LV early
      diastolic strain rate (tissue Doppler echocardiography) was smaller in group B
      than in group A at baseline. These differences and the difference in PIP/CITP
      were greatly reduced after treatment of patients in group B with spironolactone,
      with treatment having no effect on these parameters in group A. The collagen
      volume fraction was significantly correlated with PIP/CITP, LV early diastolic
      strain rate, and LV diastolic chamber stiffness for all patients before and after
      treatment with spironolactone. CONCLUSIONS: Spironolactone ameliorated LV
      diastolic dysfunction and reduced chamber stiffness in association with
      regression of myocardial fibrosis in mildly symptomatic patients with DCM. These
      effects appeared limited, however, to patients with increased myocardial collagen
      accumulation.

PMID- 16275883
TI  - Extracardiac progenitor cells repopulate most major cell types in the
      transplanted human heart.
AB  - BACKGROUND: Extracardiac progenitor cells are capable of repopulating
      cardiomyocytes at very low levels in the human heart after injury. Here, we
      explored the extent of endothelial, smooth muscle, and Schwann cell chimerism in
      patients with sex-mismatched (female-to-male) heart transplants. METHODS AND
      RESULTS: Autopsy specimens from 5 patients and endomyocardial biopsies from 7
      patients were used for this study. Endothelial, vascular smooth muscle, and
      Schwann cells were stained with antibodies against CD31 or Ulex europaeus lectin,
      smooth muscle alpha-actin, and S-100, respectively, and the Y chromosome was
      identified with in situ hybridization. Biopsy specimens from 1, 4, 6, and 12
      months and 5 and 10 years after heart transplantation were evaluated. Y-positive
      cells were counted by conventional bright-field microscopy and confirmed by
      confocal microscopy. Endothelial cells showed the highest degree of chimerism,
      averaging 24.3+/-8.2% from extracardiac sources. Schwann cells showed the next
      highest chimerism, averaging 11.2+/-2.1%; vascular smooth muscle cells averaged
      3.4+/-1.8%. All 3 cell types showed substantially higher chimerism than we
      previously observed for cardiomyocytes (0.04+/-0.05%). Endothelial chimerism was
      much higher in the microcirculation than in larger vessels. Analysis of serial
      endomyocardial biopsies revealed that high levels of endothelial chimerism
      occurred as early as 1 month after transplantation (22+/-6.6%) with no
      significant increases even up to 10 years after cardiac transplantation.
      CONCLUSIONS: Extracardiac progenitor cells are capable of repopulating most major
      cell types in the heart, but they do so with varying frequency. The signals for
      endothelial progenitor recruitment occur early and could relate to injury during
      allograft harvest or transplantation. The high degree of endothelial chimerism
      may have immune implications such as for myocardial rejection or graft
      vasculopathy.

PMID- 16275884
TI  - TLR2 and MyD88 contribute to Lactobacillus casei extract-induced focal coronary
      arteritis in a mouse model of Kawasaki disease.
AB  - BACKGROUND: Kawasaki disease is the most common cause of acquired cardiac disease
      and acute vasculitis in children, targets the coronary arteries, and can
      occasionally be fatal. The pathogenesis and the molecular mechanisms remain
      unknown. After injection of Lactobacillus casei cell-wall extract (LCCWE), mice
      develop a focal coronary arteritis that histopathologically resembles Kawasaki
      disease, but the mechanism remains unclear. Here, we tested the hypothesis that
      signaling by Toll-like receptors (TLRs) through their key downstream adaptor
      molecule myeloid differentiation factor 88 (MyD88) is required for the cellular
      activation and coronary arteritis produced by LCCWE. METHODS AND RESULTS: Bone
      marrow-derived macrophages from TLR2- or MyD88-deficient mice were unresponsive
      to LCCWE-induced stimulation. In contrast, macrophages obtained from TLR4
      deficient mice produced the same amount of interleukin-6 as macrophages from wild
      type mice after stimulation with LCCWE. Intraperitoneal injection of LCCWE
      produced severe focal coronary arteritis in TLR4(-/-) and C57BL/6 control mice
      but not in TLR2(-/-) or MyD88(-/-) mice. Collectively, these results indicate
      that LCCWE is a potent inducer of nuclear factor-kappaB via TLR2 but not TLR4 and
      that this activation proceeds via the MyD88-dependent signaling pathway. In vivo
      studies suggest that TLR2(-/-) mice are protected from LCCWE-induced coronary
      arteritis and that this protection is mediated through the adaptor molecule
      MyD88. CONCLUSIONS: Our results provide important insights into the molecular
      signaling in this mouse model of coronary arteritis. We show here that LCCWE
      induced coronary arteritis is dependent on intact TLR2 and MyD88 signaling.

PMID- 16275885
TI  - Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory
      therapy.
AB  - BACKGROUND: Vasodilatory therapy of Raynaud's phenomenon represents a difficult
      clinical problem because treatment often remains inefficient and may be not
      tolerated because of side effects. METHODS AND RESULTS: To investigate the
      effects of sildenafil on symptoms and capillary perfusion in patients with
      Raynaud's phenomenon, we performed a double-blinded, placebo-controlled, fixed
      dose, crossover study in 16 patients with symptomatic secondary Raynaud's
      phenomenon resistant to vasodilatory therapy. Patients were treated with 50 mg
      sildenafil or placebo twice daily for 4 weeks. Symptoms were assessed by diary
      cards including a 10-point Raynaud's Condition Score. Capillary flow velocity was
      measured in digital nailfold capillaries by means of a laser Doppler anemometer.
      While taking sildenafil, the mean frequency of Raynaud attacks was significantly
      lower (35+/-14 versus 52+/-18, P=0.0064), the cumulative attack duration was
      significantly shorter (581+/-133 versus 1046+/-245 minutes, P=0.0038), and the
      mean Raynaud's Condition Score was significantly lower (2.2+/-0.4 versus 3.0+/
      0.5, P=0.0386). Capillary blood flow velocity increased in each individual
      patient, and the mean capillary flow velocity of all patients more than
      quadrupled after treatment with sildenafil (0.53+/-0.09 versus 0.13+/-0.02 mm/s,
      P=0.0004). Two patients reported side effects leading to discontinuation of the
      study drug. CONCLUSIONS: Sildenafil is an effective and well-tolerated treatment
      in patients with Raynaud's phenomenon.

PMID- 16275887
TI  - Tamoxifen for the prevention of myocardial infarction in humans: preclinical and
      early clinical evidence.

PMID- 16275886
TI  - Cardiovascular interventional magnetic resonance imaging.

PMID- 16275888
TI  - LIGHT enhances the bactericidal activity of human monocytes and neutrophils via
      HVEM.
AB  - Human monocytes and neutrophils play major roles in clearing bacteria from human
      blood and tissues. We found that the herpes virus entry mediator (HVEM) was
      highly expressed in monocytes and neutrophils, and its interaction with
      "homologous to lymphotoxins, shows inducible expression, and competes with herpes
      simplex virus glycoprotein D for HVEM/tumor necrosis factor (TNF)-related 2"
      (LIGHT) enhanced bactericidal activity against Listeria monocytogenes and
      Staphylococcus aureus. The LIGHT-HVEM interaction increased levels of
      phagocytosis, interleukin (IL)-8, TNF-alpha, nitric oxide (NO), and reactive
      oxygen species (ROS) in monocytes and neutrophils. Anti-HVEM monoclonal antibody
      was able to block LIGHT-induced bactericidal activity, cytokine production (IL-8
      and TNF-alpha), and ROS generation. Moreover, inhibition of ROS and NO production
      blocked LIGHT-induced bactericidal activity. Our results indicate that the
      LIGHT/HVEM interaction in monocytes and neutrophils contributes to antibacterial
      activity.

PMID- 16275889
TI  - Elevated gelatinase activity in pulmonary alveolar proteinosis: role of
      macrophage-colony stimulating factor.
AB  - Pulmonary alveolar proteinosis (PAP) is an anti-granulocyte macrophage-colony
      stimulating factor (GM-CSF) autoimmune disease resulting in the accumulation of
      phospholipids in the alveoli. GM-CSF knockout (KO) mice exhibit a strikingly
      similar lung pathology to patients with PAP. The lack of functionally active GM
      CSF correlates with highly elevated concentrations of M-CSF in the lungs of PAP
      patients and GM-CSF KO mice. M-CSF has been associated with alternative
      macrophage activation, and in models of pulmonary fibrosis, M-CSF also
      contributes to tissue resorption and fibrosis. Matrix metalloproteinase-2 (MMP-2)
      and MMP-9 have been implicated in extracellular matrix degradation in animal
      models of fibrosis and asthma. We show for the first time that the lungs of PAP
      patients contain highly elevated levels of MMP-2 and MMP-9. PAP broncholaveolar
      lavage (BAL) cells but not bronchial epithelial cells expressed increased MMP-2
      and MMP-9 mRNA relative to healthy controls. Both MMPs were detectable as pro and
      active proteins by gelatin zymography; and by fluorometric global assay, PAP-MMP
      activity was elevated. BAL cells/fluids from GM-CSF KO mice also demonstrated
      significantly elevated MMP-2 and MMP-9 gene expression, protein, and activity.
      Finally, PAP patients undergoing GM-CSF therapy exhibited significantly reduced
      MMPs and M-CSF. These data suggest that in the absence of GM-CSF, excess M-CSF in
      PAP may redirect alveolar macrophage activation, thus potentially contributing to
      elevated MMP expression in the lung.

PMID- 16275890
TI  - Impaired NADPH oxidase activity in Rac2-deficient murine neutrophils does not
      result from defective translocation of p47phox and p67phox and can be rescued by
      exogenous arachidonic acid.
AB  - Rac2 is a hematopoietic-specific Rho-GTPase that plays a stimulus-specific role
      in regulating reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      activation and other functional responses in neutrophils. In this study, rac2-/-
      neutrophils were shown to have significantly decreased NADPH oxidase activity and
      actin remodeling in response to exogenous arachidonic acid (AA), as previously
      observed for phorbol 12-myristate 13-acetate (PMA) or formyl-Met-Leu-Phe (fMLP)
      as agonists. PMA-, fMLP-, or AA-induced translocation of p47phox and p67phox to
      the plasma membrane was not impaired in rac2-/- neutrophils. Combined stimulation
      of rac2-/- neutrophils with exogenous AA and PMA had a synergistic effect on
      NADPH oxidase activity, and superoxide production increased to a level that was
      at least as high as wild-type cells and had no effect on fMLP-elicited enzyme
      activity. Membrane translocation of p47phox and p67phox as well as Rac1
      activation was not increased further by combined PMA and AA stimulation.
      Inhibitor studies were consistent with important roles for phorbol ester
      activated protein kinase C (PKC) isoforms and an atypical isoform, PKCzeta, in
      superoxide production by wild-type and rac2-/- neutrophils stimulated with AA and
      PMA. In addition, PMA-stimulated release of AA and cytoplasmic phospholipase A2
      expression in rac2-/- neutrophils were similar to wild-type, suggesting that
      deficient AA production by PMA-stimulated rac2-/- neutrophils does not explain
      the effect of exogenous AA on oxidase activity. Although not required for
      translocation of p47phox and p67phox, Rac2 is necessary for optimal activity of
      the assembled oxidase complex, an effect that can be replaced by exogenous AA,
      which may act directly or via an exogenous AA-induced mediator.

PMID- 16275891
TI  - Regulation of matrix metalloproteinase-9 (MMP-9) in TNF-stimulated neutrophils:
      novel pathways for tertiary granule release.
AB  - Matrix metalloproteinase-9 (MMP-9) is present in the tertiary granules of
      neutrophils and is rapidly released following stimulation. We examined the
      pathways that regulate tumor necrosis factor (TNF)-mediated MMP-9 release and
      found this to be dependent on the TNF receptor I. TNF rapidly activated
      extracellular signal-regulated kinase and p38 mitogen-activated protein kinases,
      but neither of these pathways was critical for MMP-9 release. Many neutrophil
      responses to TNF require beta2-integrin-dependent signaling and subsequent Src
      family kinase activation. In contrast, we found that MMP-9 release from tertiary
      granules was only partially affected by blocking beta2-integrin-mediated
      adhesion. Similarly, blocking Src family kinases with the inhibitor PP2 only
      attenuated TNF-induced MMP-9 release. Blocking beta2-integrin-mediated adhesion
      and Src family kinases did not result in additive inhibition of MMP-9 release. In
      contrast, inhibiting protein kinase C (PKC) with a pan-specific inhibitor blocked
      greater than 85% of MMP-9 release. Inhibitors against specific PKC isoforms
      suggested a role for PKC alpha and PKC delta in maximal MMP-9 release. These data
      suggest that MMP-9 release from tertiary granules uses beta2-integrin-independent
      signaling pathways. Furthermore, PKC isoforms play a critical role in regulating
      tertiary granule release.

PMID- 16275892
TI  - Chemokine receptors Ccr1, Ccr2, and Ccr5 mediate neutrophil migration to
      postischemic tissue.
AB  - Leukocyte infiltration of reperfused tissue is a key event in the pathogenesis of
      ischemia-reperfusion. However, the role of chemokine receptors Ccr1, Ccr2, and
      Ccr5 for each single step of the postischemic recruitment process of leukocytes
      has not yet been characterized. Leukocyte rolling, firm adherence,
      transendothelial, and extravascular migration were analyzed in the cremaster
      muscle of anaesthetized C57BL/6 mice using near-infrared reflected light oblique
      transillumination microscopy. Prior to 30 min of ischemia as well as at 5, 30,
      60, 90, and 120 min after onset of reperfusion, migration parameters were
      determined in wild-type, Ccr1-/-, Ccr2-/-, and Ccr5-/- mice. Sham-operated wild
      type mice without ischemia were used as controls. No differences were detected in
      numbers of rolling leukocytes among groups. In contrast, the number of firmly
      adherent leukocytes was increased significantly in wild-type mice as compared
      with sham-operated mice throughout the entire reperfusion phase. Already after 5
      min of reperfusion, this increase was reduced significantly in Ccr1-/- and Ccr5-/
      mice, whereas only in Ccr2-/- mice, was adherence attenuated significantly at
      120 min after onset of reperfusion. Furthermore, after 120 min of reperfusion,
      the number of transmigrated leukocytes (>80% Ly-6G+ neutrophils) was elevated in
      wild-type mice as compared with sham-operated animals. This elevation was
      significantly lower in Ccr1-/-, Ccr2-/-, and Ccr5-/- mice. Leukocyte
      extravascular migration distances were comparable among groups. In conclusion,
      these in vivo data demonstrate that Ccr1, Ccr2, and Ccr5 mediate the postischemic
      recruitment of neutrophils through effects on intravascular adherence and
      subsequent transmigration.

PMID- 16275893
TI  - Chemical inhibitors of TNF signal transduction in human neutrophils point to
      distinct steps in cell activation.
AB  - Chemical screening identified three small compounds that selectively inhibited
      activation of the respiratory burst (RB) of human neutrophils in response to
      tumor necrosis factor (TNF) and formylated peptide but not phorbol ester and
      spared the ability of neutrophils to kill bacteria. These compounds partially
      inhibited TNF-triggered cytoskeletal rearrangements without blocking adhesion or
      transmigation of polymorphonuclear neutrophils through TNF-activated monolayers
      of endothelial cells. The compounds were nontoxic to neutrophils and endothelial
      cells. They had no direct inhibitory effect on the tyrosine kinases Src, Syk, or
      Pyk2. However, their differential effects on cell spreading, bacteria-induced RB,
      TNF-induced degranulation, TNF-induced protein tyrosine phosphorylation, and TNF
      induced Syk activation suggested that each may act on different elements of
      neutrophil signaling pathways.

PMID- 16275894
TI  - Virulent clinical isolates of Mycobacterium tuberculosis grow rapidly and induce
      cellular necrosis but minimal apoptosis in murine macrophages.
AB  - In this study, we investigated the ability of four clinical isolates of
      Mycobacterium tuberculosis representing a range of virulence for their capacity
      to grow in bone marrow-derived macrophages. The rate of growth of each of the
      isolates in macrophages reflected their known virulence, but the most virulent
      isolates strongly induced production of the cytokine tumor necrosis factor alpha.
      A key difference, however, was the degree of cell cytotoxicity observed with the
      more virulent strains after several days in culture. Staining of cell monolayers
      for DNA fragmentation indicative of apoptosis showed that this was minimal and
      only evident to any degree in macrophages infected with the most virulent
      strains. In contrast, electron microscopy revealed damage of macrophages
      consistent with cell necrosis. These results suggest that rapid intracellular
      growth rate and induction of necrotic cell death within host macrophages are
      virulence factors of M. tuberculosis in the early stages of bacterial infection.
      They further imply that infected cell apoptosis, regarded as a defense mechanism
      or cross-priming mechanism, plays a minimal role.

PMID- 16275895
TI  - Bovine natural killer cells acquire cytotoxic/effector activity following
      activation with IL-12/15 and reduce Mycobacterium bovis BCG in infected
      macrophages.
AB  - Bovine natural killer (NK) cells were recently identified by positive selection
      of a NK cell-activating receptor p46 (NKp46)+ CD3- lymphocyte population, which
      expresses CD25 and CD8 and lyses tumor cell lines following stimulation with
      recombinant interleukin-2. In the current work, we characterize the
      cytotoxic/effector potential of a CD3(-)CD8(-)CD11b- population isolated through
      negative selection of bovine peripheral blood leukocytes. This population is
      CD25(lo)CD62(hi) when isolated and becomes CD25hiCD62L(lo) following cytokine
      stimulation. Activated bovine NK cells increase expression of granulysin,
      interferon-gamma, and perforin and have cytotoxic activity against human tumor
      cells and Mycobacterium bovis bacillus Calmette-Guerin-infected alveolar and
      monocyte-derived macrophages. Expression of a bovine homologue of the CD56 neural
      adhesion molecule expressed by human NK cells was detected in mRNA from brain
      tissue but was not detected in peripheral blood mononuclear cells or purified NK
      cell mRNA. Analysis of mRNA from nonstimulated peripheral blood NK cells
      demonstrates the constitutive expression of homologues of human NK receptors
      NKp46, CD244, and CD94 and the granule proteins granulysin and perforin. Phorbol
      ester-stimulated CD8+ T cells also expressed CD244 and CD94, and CD4+ T cells
      expressed CD94. These NK cell receptors bearing T lymphocytes may represent
      memory subsets characterized in humans. The results of these studies demonstrate
      that bovine NK cells may play an important role in the innate immune responses of
      cattle.

PMID- 16275896
TI  - Prostaglandin E2 promotes degranulation-independent release of MCP-1 from mast
      cells.
AB  - Mast cells (MCs) are common components of inflammatory infiltrates and a source
      of proangiogenic factors. Inflammation is often accompanied by vascular changes.
      However, little is known about modulation of MC-derived proangiogenic factors
      during inflammation. In this study, we evaluated the effects of the
      proinflammatory mediator prostaglandin E2 (PGE2) on MC expression and release of
      proangiogenic factors. We report that PGE2 dose-dependently induces primary MCs
      to release the proangiogenic chemokine monocyte chemoattractant protein-1 (MCP
      1). This release of MCP-1 is complete by 2 h after PGE2 exposure, reaches levels
      of MCP-1 at least 15-fold higher than background, and is not accompanied by
      degranulation or increased MCP-1 gene expression. By immunoelectron microscopy,
      MCP-1 is detected within MCs at a cytoplasmic location distinct from the
      secretory granules. Dexamethasone and cyclosporine A inhibit PGE2-induced MCP-1
      secretion by approximately 60%. Agonists of PGE2 receptor subtypes revealed that
      the EP1 and EP3 receptors can independently mediate MCP-1 release from MCs. These
      observations identify PGE2-induced MCP-1 release from MCs as a pathway underlying
      inflammation-associated angiogenesis and extend current understanding of the
      activities of PGE2.

PMID- 16275897
TI  - Cationic liposomes induce apoptosis through p38 MAP kinase-caspase-8-Bid pathway
      in macrophage-like RAW264.7 cells.
AB  - We have demonstrated that cationic liposomes composed of stearylamine (SA
      liposomes) induce apoptosis in a variety of cells, but the mechanism responsible
      for the cellular death is not clear. In this paper, we investigated the signaling
      pathways implicated in SA-liposome-induced apoptosis in the macrophage-like cell
      line RAW264.7. Treatment with SA-liposomes caused the activation of mitogen
      activated protein kinases (MAPKs), especially p38 and c-jun N-terminal kinase,
      and apoptosis was only inhibited upon the addition of a specific inhibitor for
      p38. N-acetylcysteine, a scavenger of reactive oxygen species (ROS), effectively
      inhibited the activation of p38 and cellular death, indicating that the
      activation induced by ROS is an initial step in the process of apoptosis
      triggered by SA-liposomes. Caspase-8 was activated by p38, and caspase-8
      dependent cleavage of Bid was also observed. No down-regulation of bcl-2
      expression, and no cleavage of Bax protein were observed. Taken together, our
      results suggest that apoptosis of RAW264.7 by SA-liposomes was mediated by the
      MAPK p38 and a caspase-8-dependent Bid-cleavage pathway. Moreover, we found that
      ROS can contribute intimately to the SA-liposome-induced cell death in RAW264.7.

PMID- 16275898
TI  - Reproductive fitness and tooth wear: milking as much as possible out of dental
      topographic analysis.

PMID- 16275899
TI  - Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments
      learning and lowers Alzheimer beta-amyloid peptide in rodent.
AB  - Like acetylcholinesterase, butyrylcholinesterase (BChE) inactivates the
      neurotransmitter acetylcholine (ACh) and is hence a viable therapeutic target in
      Alzheimer's disease, which is characterized by a cholinergic deficit. Potent,
      reversible, and brain-targeted BChE inhibitors (cymserine analogs) were developed
      based on binding domain structures to help elucidate the role of this enzyme in
      the central nervous system. In rats, cymserine analogs caused long-term
      inhibition of brain BChE and elevated extracellular ACh levels, without
      inhibitory effects on acetylcholinesterase. In rat brain slices, selective BChE
      inhibition augmented long-term potentiation. These compounds also improved the
      cognitive performance (maze navigation) of aged rats. In cultured human SK-N-SH
      neuroblastoma cells, intra- and extracellular beta-amyloid precursor protein, and
      secreted beta-amyloid peptide levels were reduced without affecting cell
      viability. Treatment of transgenic mice that overexpressed human mutant amyloid
      precursor protein also resulted in lower beta-amyloid peptide brain levels than
      controls. Selective, reversible inhibition of brain BChE may represent a
      treatment for Alzheimer's disease, improving cognition and modulating
      neuropathological markers of the disease.

PMID- 16275900
TI  - Sustaining intrinsic growth capacity of adult neurons promotes spinal cord
      regeneration.
AB  - The peripheral axonal branch of primary sensory neurons readily regenerates after
      peripheral nerve injury, but the central branch, which courses in the dorsal
      columns of the spinal cord, does not. However, if a peripheral nerve is
      transected before a spinal cord injury, sensory neurons that course in the dorsal
      columns will regenerate, presumably because their intrinsic growth capacity is
      enhanced by the priming peripheral nerve lesion. As the effective priming lesion
      is made before the spinal cord injury it would clearly have no clinical utility,
      and unfortunately, a priming lesion made after a spinal cord injury results in an
      abortive regenerative response. Here, we show that two priming lesions, one made
      at the time of a spinal cord injury and a second 1 week after a spinal cord
      injury, in fact, promote dramatic regeneration, within and beyond the lesion. The
      first lesion, we hypothesize, enhances intrinsic growth capacity, and the second
      one sustains it, providing a paradigm for promoting CNS regeneration after
      injury.

PMID- 16275901
TI  - Profile of Jeffrey C. Hall.

PMID- 16275902
TI  - Pleistocene to recent dietary shifts in California condors.
AB  - We used carbon and nitrogen isotopes to investigate changes in the diet of
      California condors from the Pleistocene to the recent. During the Pleistocene,
      condors from California fed on both terrestrial megafauna and marine mammals.
      Early accounts reported condors feeding on the carcasses of marine mammals, but
      by the late 1700s, condor diets had shifted predominantly to terrestrial animals,
      following the commercial harvesting of marine mammals and the development of
      cattle ranching on land. At present, dairy calves provided by humans
      significantly augment condor diet, constituting an artificial support of the
      current population. Reestablishing a marine mammal component in the condor diet
      may be an effective strategy for fostering viable condor populations independent
      of direct human subsidies.

PMID- 16275903
TI  - Leucine-rich repeat kinase 2: a new player with a familiar theme for Parkinson's
      disease pathogenesis.

PMID- 16275904
TI  - The transduction of the nitrogen regulation signal in Saccharomyces cerevisiae.
AB  - In cells of Saccharomyces cerevisiae, using ammonia as a source of nitrogen,
      Gln3p is sequestered in the cytoplasm by Ure2p but enters the nucleus when the
      cells are shifted to a nonpreferred source of nitrogen such as proline. The
      interpretation of recently published observations provides evidence for the view
      that Ure2p is the sensor for a drop in the intracellular concentration of
      glutamine, a signal that results in the polyubiquitination of the vesicle
      responsible for retaining the Gln3p-Ure2p complex in the cytoplasm. As a
      consequence of the drop in glutamine concentration, Gln3p is able to enter the
      nucleus and to activate the transcription of nitrogen-regulated genes.

PMID- 16275905
TI  - Actin-bound structures of Wiskott-Aldrich syndrome protein (WASP)-homology domain
      2 and the implications for filament assembly.
AB  - Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) is a small and
      widespread actin-binding motif. In the WASP family, WH2 plays a role in filament
      nucleation by Arp2/3 complex. Here we describe the crystal structures of
      complexes of actin with the WH2 domains of WASP, WASP-family verprolin homologous
      protein, and WASP-interacting protein. Despite low sequence identity, WH2 shares
      structural similarity with the N-terminal portion of the actin monomer
      sequestering thymosin beta domain (Tbeta). We show that both domains inhibit
      nucleotide exchange by targeting the cleft between actin subdomains 1 and 3, a
      common binding site for many unrelated actin-binding proteins. Importantly, WH2
      is significantly shorter than Tbeta but binds actin with approximately 10-fold
      higher affinity. WH2 lacks a C-terminal extension that in Tbeta4 becomes involved
      in monomer sequestration by interfering with intersubunit contacts in F-actin.
      Owing to their shorter length, WH2 domains connected in tandem by short linkers
      can coexist with intersubunit contacts in F-actin and are proposed to function in
      filament nucleation by lining up actin subunits along a filament strand. The WH2
      central region of WASP-family proteins is proposed to function in an analogous
      way by forming a special class of tandem repeats whose function is to line up
      actin and Arp2 during Arp2/3 nucleation. The structures also suggest a mechanism
      for how profilin-binding Pro-rich sequences positioned N-terminal to WH2 could
      feed actin monomers directly to WH2, thereby playing a role in filament
      elongation.

PMID- 16275906
TI  - Human C4b-binding protein selectively interacts with Neisseria gonorrhoeae and
      results in species-specific infection.
AB  - Neisseria gonorrhoeae is the causative agent of gonorrhea, a disease that is
      restricted to humans. Complement forms a key arm of the innate immune system that
      combats gonococcal infections. N. gonorrhoeae uses its outer membrane porin (Por)
      molecules to bind the classical pathway of complement down-regulatory protein C4b
      binding protein (C4bp) to evade killing by human complement. Strains of N.
      gonorrhoeae that resisted killing by human serum complement were killed by serum
      from rodent, lagomorph, and primate species, which cannot be readily infected
      experimentally with this organism and whose C4bp molecules did not bind to N.
      gonorrhoeae. In contrast, we found that Yersinia pestis, an organism that can
      infect virtually all mammals, bound species-specific C4bp and uniformly resisted
      serum complement-mediated killing by these species. Serum resistance of gonococci
      was restored in these sera by human C4bp. An exception was serotype Por1B-bearing
      gonococcal strains that previously had been used successfully in a chimpanzee
      model of gonorrhea that simulates human disease. Por1B gonococci bound chimpanzee
      C4bp and resisted killing by chimpanzee serum, providing insight into the host
      restriction of gonorrhea and addressing why Por1B strains, but not Por1A strains,
      have been successful in experimental chimpanzee infection. Our findings may lead
      to the development of better animal models for gonorrhea and may also have
      implications in the choice of complement sources to evaluate neisserial vaccine
      candidates.

PMID- 16275907
TI  - Identification of an Escherichia coli O157:H7 heme oxygenase with tandem
      functional repeats.
AB  - Heme oxygenases (HOs) catalyze the oxidation of heme to biliverdin, carbon
      monoxide (CO), and free iron. Iron acquisition is critical for invading
      microorganisms to enable survival and growth. Here we report the crystal
      structure of ChuS, which displays a previously uncharacterized fold and is unique
      compared with other characterized HOs. Despite only 19% sequence identity between
      the N- and C-terminal halves, these segments of ChuS represent a structural
      duplication, with a root-mean-square deviation of 2.1 A between the two repeats.
      ChuS is capable of using ascorbic acid or cytochrome P450 reductase-NADPH as
      electron sources for heme oxygenation. CO detection confirmed that ChuS is a HO,
      and we have identified it in pathogenic Escherichia coli O157:H7. Based on
      sequence analysis, this HO is present in many bacteria, although not in the E.
      coli K-12 strain. The N- and C-terminal halves of ChuS are each a functional HO.

PMID- 16275908
TI  - Microevolution and mega-icebergs in the Antarctic.
AB  - Microevolution is regarded as changes in the frequencies of genes in populations
      over time. Ancient DNA technology now provides an opportunity to demonstrate
      evolution over a geological time frame and to possibly identify the causal
      factors in any such evolutionary event. Using nine nuclear microsatellite DNA
      loci, we genotyped an ancient population of Adelie penguins (Pygoscelis adeliae)
      aged approximately 6,000 years B.P. Subfossil bones from this population were
      excavated by using an accurate stratigraphic method that allowed the
      identification of individuals even within the same layer. We compared the allele
      frequencies in the ancient population with those recorded from the modern
      population at the same site in Antarctica. We report significant changes in the
      frequencies of alleles between these two time points, hence demonstrating
      microevolutionary change. This study demonstrates a nuclear gene-frequency change
      over such a geological time frame. We discuss the possible causes of such a
      change, including the role of mutation, genetic drift, and the effects of gene
      mixing among different penguin populations. The latter is likely to be
      precipitated by mega-icebergs that act to promote migration among penguin
      colonies that typically show strong natal return.

PMID- 16275909
TI  - Disruption of a Plasmodium falciparum gene linked to male sexual development
      causes early arrest in gametocytogenesis.
AB  - A male gametocyte defect in the Plasmodium falciparum Dd2 parasite was previously
      discovered through the observation that all progeny clones in a Dd2 x HB3 genetic
      cross were the result of fertilization events between Dd2 female and HB3 male
      gametes. A determinant linked to the defect in Dd2 was subsequently mapped to an
      800-kb segment on chromosome 12. Here, we report further mapping of the
      determinant to an 82-kb region and the identification of a candidate gene, P.
      falciparum male development gene 1 (pfmdv-1), that is expressed at a lower level
      in Dd2 compared with the wild-type normal male gametocyte-producing ancestor W2.
      Pfmdv-1 protein is sexual-stage specific and is located on the gametocyte plasma
      membrane, parasitophorous vacuole membrane, and the membranes of cleft-like
      structures within the erythrocyte. Disruption of pfmdv-1 results in a dramatic
      reduction in mature gametocytes, especially functional male gametocytes, with the
      majority of sexually committed parasites developmentally arrested at stage I. The
      pfmdv-1-knockout parasites show disturbed membrane structures, particularly
      multimembrane vesicles/tubes that likely derive from deformed cleft-like
      structures. Mosquito infectivity of the knockout parasites was also greatly
      reduced but not completely lost. The results suggest that pfmdv-1 plays a key
      role in gametocyte membrane formation and integrity.

PMID- 16275910
TI  - Control of mammalian glycogen synthase by PAS kinase.
AB  - The regulation of glycogen metabolism is critical for the maintenance of glucose
      and energy homeostasis in mammals. Glycogen synthase, the enzyme responsible for
      glycogen production, is regulated by multisite phosphorylation in yeast and
      mammals. We have previously identified PAS kinase as a physiological regulator of
      glycogen synthase in Saccharomyces cerevisiae. We provide evidence here that PAS
      kinase is an important regulator of mammalian glycogen synthase. Glycogen
      synthase is efficiently phosphorylated by PAS kinase in vitro at Ser-640, a known
      regulatory phosphosite. Efficient phosphorylation requires a region of PAS kinase
      outside the catalytic domain. This region appears to mediate a direct interaction
      between glycogen synthase and PAS kinase, thereby targeting kinase activity to
      this substrate specifically. This interaction is regulated by the PAS kinase PAS
      domain, raising the possibility that this interaction (and phosphorylation event)
      is modulated by the cellular metabolic state. This mode of regulation provides a
      mechanism for metabolic status to impinge directly on the cellular decision of
      whether to store or use available energy.

PMID- 16275912
TI  - Resistance to inhibitors of cholinesterase 8A catalyzes release of Galphai-GTP
      and nuclear mitotic apparatus protein (NuMA) from NuMA/LGN/Galphai-GDP complexes.
AB  - Resistance to inhibitors of cholinesterase (Ric) 8A is a guanine nucleotide
      exchange factor that activates certain G protein alpha-subunits. Genetic studies
      in Caenorhabditis elegans and Drosophila melanogaster have placed RIC-8 in a
      previously uncharacterized G protein signaling pathway that regulates centrosome
      movements during cell division. Components of this pathway include G protein
      subunits of the Galphai class, GPR or GoLoco domain-containing proteins, RGS
      (regulator of G protein signaling) proteins, and accessory factors. These
      proteins interact to regulate microtubule pulling forces during mitotic movement
      of chromosomes. It is unclear how the GTP-binding and hydrolysis cycle of Galphai
      functions in the context of this pathway. In mammals, the GoLoco domain
      containing protein LGN (GPSM2), the LGN- and microtubule-binding nuclear mitotic
      apparatus protein (NuMA), and Galphai regulate a similar process. We find that
      mammalian Ric-8A dissociates Galphai-GDP/LGN/NuMA complexes catalytically,
      releasing activated Galphai-GTP in vitro. Ric-8A-stimulated activation of Galphai
      caused concomitant liberation of NuMA from LGN. We conclude that Ric-8A
      efficiently utilizes GoLoco/Galphai-GDP complexes as substrates in vitro and
      suggest that Ric-8A-stimulated release of Galphai-GTP and/or NuMA regulates the
      microtubule pulling forces on centrosomes during cell division.

PMID- 16275911
TI  - WNK3 modulates transport of Cl- in and out of cells: implications for control of
      cell volume and neuronal excitability.
AB  - The regulation of Cl(-) transport into and out of cells plays a critical role in
      the maintenance of intracellular volume and the excitability of GABA responsive
      neurons. The molecular determinants of these seemingly diverse processes are
      related ion cotransporters: Cl(-) influx is mediated by the Na-K-2Cl
      cotransporter NKCC1 and Cl(-) efflux via K-Cl cotransporters, KCC1 or KCC2. A Cl(
      )/volume-sensitive kinase has been proposed to coordinately regulate these
      activities via altered phosphorylation of the transporters; phosphorylation
      activates NKCC1 while inhibiting KCCs, and dephosphorylation has the opposite
      effects. We show that WNK3, a member of the WNK family of serine-threonine
      kinases, colocalizes with NKCC1 and KCC1/2 in diverse Cl(-)-transporting
      epithelia and in neurons expressing ionotropic GABA(A) receptors in the
      hippocampus, cerebellum, cerebral cortex, and reticular activating system. By
      expression studies in Xenopus oocytes, we show that kinase-active WNK3 increases
      Cl(-) influx via NKCC1, and that it inhibits Cl(-) exit through KCC1 and KCC2;
      kinase-inactive WNK3 has the opposite effects. WNK3's effects are imparted via
      altered phosphorylation and surface expression of its downstream targets and
      bypass the normal requirement of altered tonicity for activation of these
      transporters. Together, these data indicate that WNK3 can modulate the level of
      intracellular Cl(-) via opposing actions on entry and exit pathways. They suggest
      that WNK3 is part of the Cl(-)/volume-sensing mechanism necessary for the
      maintenance of cell volume during osmotic stress and the dynamic modulation of
      GABA neurotransmission.

PMID- 16275913
TI  - WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl-
      cotransporters required for normal blood pressure homeostasis.
AB  - WNK1 and WNK4 [WNK, with no lysine (K)] are serine-threonine kinases that
      function as molecular switches, eliciting coordinated effects on diverse ion
      transport pathways to maintain homeostasis during physiological perturbation.
      Gain-of-function mutations in either of these genes cause an inherited syndrome
      featuring hypertension and hyperkalemia due to increased renal NaCl reabsorption
      and decreased K(+) secretion. Here, we reveal unique biochemical and functional
      properties of WNK3, a related member of the WNK kinase family. Unlike WNK1 and
      WNK4, WNK3 is expressed throughout the nephron, predominantly at intercellular
      junctions. Because WNK4 is a potent inhibitor of members of the cation
      cotransporter SLC12A family, we used coexpression studies in Xenopus oocytes to
      investigate the effect of WNK3 on NCC and NKCC2, related kidney-specific
      transporters that mediate apical NaCl reabsorption in the thick ascending limb
      and distal convoluted tubule, respectively. In contrast to WNK4's inhibitory
      activity, kinase-active WNK3 is a potent activator of both NKCC2 and NCC-mediated
      transport. Conversely, in its kinase-inactive state, WNK3 is a potent inhibitor
      of NKCC2 and NCC activity. WNK3 regulates the activity of these transporters by
      altering their expression at the plasma membrane. Wild-type WNK3 increases and
      kinase-inactive WNK3 decreases NKCC2 phosphorylation at Thr-184 and Thr-189,
      sites required for the vasopressin-mediated plasmalemmal translocation and
      activation of NKCC2 in vivo. The effects of WNK3 on these transporters and their
      coexpression in renal epithelia implicate WNK3 in NaCl, water, and blood pressure
      homeostasis, perhaps via signaling downstream of vasopressin.

PMID- 16275915
TI  - An index to quantify an individual's scientific research output.
AB  - I propose the index h, defined as the number of papers with citation number > or
      =h, as a useful index to characterize the scientific output of a researcher.

PMID- 16275914
TI  - Molecular evidence for arterial repair in atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory process and progresses through
      characteristic morphologic stages. We have shown previously that chronically
      injecting bone-marrow-derived vascular progenitor cells can effect arterial
      repair. This repair capacity depends on the age of the injected marrow cells,
      suggesting a progressive decline in progenitor cell function. We hypothesized
      that the progression of atherosclerosis coincides with the deteriorating repair
      capacity of the bone marrow. Here, we ascribe patterns of gene expression that
      accurately and reproducibly identify specific disease states in murine
      atherosclerosis. We then use these expression patterns to determine the point in
      the disease process at which the repair of arteries by competent bone marrow
      cells ceases to be efficient. We show that the loss of the molecular signature
      for competent repair is concurrent with the initiation of atherosclerotic
      lesions. This work provides a previously unreported comprehensive molecular data
      set using broad-based analysis that links the loss of successful repair with the
      progression of a chronic illness.

PMID- 16275916
TI  - Computational redesign of human butyrylcholinesterase for anticocaine medication.
AB  - Molecular dynamics was used to simulate the transition state for the first
      chemical reaction step (TS1) of cocaine hydrolysis catalyzed by human
      butyrylcholinesterase (BChE) and its mutants. The simulated results demonstrate
      that the overall hydrogen bonding between the carbonyl oxygen of (-)-cocaine
      benzoyl ester and the oxyanion hole of BChE in the TS1 structure for (-)-cocaine
      hydrolysis catalyzed by A199S/S287G/A328W/Y332G BChE should be significantly
      stronger than that in the TS1 structure for (-)-cocaine hydrolysis catalyzed by
      the WT BChE and other simulated BChE mutants. Thus, the transition-state
      simulations predict that A199S/S287G/A328W/Y332G mutant of BChE should have a
      significantly lower energy barrier for the reaction process and, therefore, a
      significantly higher catalytic efficiency for (-)-cocaine hydrolysis. The
      theoretical prediction has been confirmed by wet experimental tests showing an
      approximately (456 +/- 41)-fold improved catalytic efficiency of
      A199S/S287G/A328W/Y332G BChE against (-)-cocaine. This is a unique study to
      design an enzyme mutant based on transitionstate simulation. The designed BChE
      mutant has the highest catalytic efficiency against cocaine of all of the
      reported BChE mutants, demonstrating that the unique design approach based on
      transition-state simulation is promising for rational enzyme redesign and drug
      discovery.

PMID- 16275917
TI  - Genetic diversity and reproductive success in mandrills (Mandrillus sphinx).
AB  - Recent studies of wild animal populations have shown that estimators of neutral
      genetic diversity, such as mean heterozygosity, are often correlated with various
      fitness traits, such as survival, disease susceptibility, or reproductive
      success. We used two estimators of genetic diversity to explore the relationship
      between heterozygosity and reproductive success in male and female mandrills
      (Mandrillus sphinx) living in a semifree ranging setting in Gabon. Because social
      rank is known to influence reproductive success in both sexes, we also examined
      the correlation between genetic diversity and social rank in females, and
      acquisition of alpha status in males, as well as length of alpha male tenure. We
      found that heterozygous individuals showed greater reproductive success, with
      both females and males producing more offspring. However, heterozygosity
      influenced reproductive success only in dominant males, not in subordinates.
      Neither the acquisition of alpha status in males, nor social rank in females, was
      significantly correlated with heterozygosity, although more heterozygous alpha
      males showed longer tenure than homozygous ones. We also tested whether the
      benefits of greater genetic diversity were due mainly to a genome-wide effect of
      inbreeding depression or to heterosis at one or a few loci. Multilocus effects
      best explained the correlation between heterozygosity and reproductive success
      and tenure, indicating the occurrence of inbreeding depression in this mandrill
      colony.

PMID- 16275918
TI  - X-ray absorption spectroscopy of chloroperoxidase compound I: Insight into the
      reactive intermediate of P450 chemistry.
AB  - We report the structural characterization of a thiolate-ligated ferryl radical.
      Using x-ray absorption spectroscopy, we examined chloroperoxidase (CPO) compound
      I (CPO-I). Our results indicate that CPO-I is an authentic ferryl species with an
      Fe-O bond of 1.65 A. Axial-ligand interactions result in a remarkably long 2.48-A
      Fe-S bond. Analogous forms of cytochrome P450 and CPO have been shown to possess
      virtually identical coordination environments. Thus, it seems likely that our
      findings provide a good structural description of the elusive P450-I.

PMID- 16275919
TI  - Sensory suppression during feeding.
AB  - Feeding is essential for survival, whereas withdrawal and escape reactions are
      fundamentally protective. These critical behaviors can compete for an animal's
      resources when an acutely painful stimulus affects the animal during feeding. One
      solution to the feeding-withdrawal conflict is to optimize feeding by suppressing
      pain. We examined whether rats continue to feed when challenged with a painful
      stimulus. During feeding, motor withdrawal responses to noxious paw heat either
      did not occur or were greatly delayed. To investigate the neural basis of sensory
      suppression accompanying feeding, we recorded from brainstem pain-modulatory
      neurons involved in the descending control of pain transmission. During feeding,
      pain-facilitatory ON cells were inhibited and pain-inhibitory OFF cells were
      excited. When a nonpainful somatosensory stimulus preactivated ON cells and
      preinhibited OFF cells, rats interrupted eating to react to painful stimuli.
      Inactivation of the brainstem region containing ON and OFF cells also blocked
      pain suppression during eating, demonstrating that brainstem pain-modulatory
      neurons suppress motor reactions to external stimulation during homeostatic
      behaviors.

PMID- 16275920
TI  - Androgens regulate the permeability of the blood-testis barrier.
AB  - Within the mammalian testis, specialized tight junctions between somatic Sertoli
      cells create basal and apical polarity within the cells, restrict movement of
      molecules between cells, and separate the seminiferous epithelium into basal and
      adluminal compartments. These tight junctions form the basis of the blood-testis
      barrier, a structure whose function and dynamic regulation is poorly understood.
      In this study, we used microarray gene expression profiling to identify genes
      with altered transcript levels in a mouse model for conditional androgen
      insensitivity. We show that testosterone, acting through its receptor expressed
      in Sertoli cells, regulates the expression of claudin 3, which encodes a
      transient component of newly formed tight junctions. Sertoli cell-specific
      ablation of androgen receptor results in increased permeability of the blood
      testis barrier to biotin, suggesting claudin 3 regulates the movement of small
      molecules across the Sertoli cell tight junctions. These results suggest that
      androgen action in Sertoli cells regulates germ cell differentiation, in part by
      controlling the microenvironment of the seminiferous epithelium. Our studies also
      indicate that hormonal strategies for male contraception may interfere with the
      blood-testis barrier.

PMID- 16275921
TI  - Modulation of surgical fibrosis by microbial zwitterionic polysaccharides.
AB  - Bacterial carbohydrates have long been considered T cell-independent antigens
      that primarily induce humoral immune responses. Recently, it has been
      demonstrated that bacterial capsules that possess a zwitterionic charge motif can
      activate CD4(+) T cells after processing and presentation by antigen-presenting
      cells. Here we show that these zwitterionic polysaccharides can prevent T helper
      1-mediated fibrosis by signaling for the release of IL-10 from CD4(+) T cells in
      vivo. IL-10 production by these T cells and their ability to prevent fibrosis is
      controlled by the inducible costimulator (ICOS)-ICOS ligand pathway. These data
      demonstrate that the interaction of the zwitterionic polysaccharides with T cells
      results in modulation of surgical fibrosis in vivo and suggest a previously
      undescribed approach to "harnessing" T cell function to prevent inflammatory
      tissue disorders in humans.

PMID- 16275922
TI  - Cyclin H binding to the RARalpha activation function (AF)-2 domain directs
      phosphorylation of the AF-1 domain by cyclin-dependent kinase 7.
AB  - The transcriptional activity of nuclear retinoic acid receptors (RARs), which act
      as RAR/retinoid X receptor (RXR) heterodimers, depends on two activation
      functions, AF-1 and AF-2, which are targets for phosphorylations and synergize
      for the activation of retinoic acid target genes. The N-terminal AF-1 domain of
      RARalpha is phosphorylated at S77 by the cyclin-dependent kinase (cdk)-activating
      kinase (CAK) subcomplex (cdk7/cyclin H/MAT1) of the general transcription factor
      TFIIH. Here, we show that phosphorylation of S77 governing the transcriptional
      activity of RARalpha depends on cyclin H binding at a RARalpha region that
      encompasses loop 8-9 and the N-terminal tip of helix 9 of the AF-2 domain. We
      propose a model in which the structural constraints of this region control the
      architecture of the RAR/RXR/TFIIH complex and therefore the efficiency of
      RARalpha phosphorylation by cdk7. To our knowledge, this study provides the first
      example of a cooperation between the AF-2 and AF-1 domains of RARs through a
      kinase complex.

PMID- 16275923
TI  - RhlB helicase rather than enolase is the beta-subunit of the Escherichia coli
      polynucleotide phosphorylase (PNPase)-exoribonucleolytic complex.
AB  - Escherichia coli polynucleotide phosphorylase (PNPase), a protein that has both
      ribonucleolytic and synthetic capabilities, binds, along with the 48-kDa
      glycolytic enzyme enolase, the 50-kDa DEAD-box protein RhlB helicase and other
      cellular proteins to the C-terminal "scaffold" region of RNase E to form a
      complex termed the RNA degradosome. PNPase itself has been reported to exist as a
      complex (alpha(3)beta(2)) containing trimers of a catalytic subunit (alpha) and
      dimers of another subunit (beta). The beta-subunit has been believed to be
      enolase; we report here that it is instead the RhlB helicase. Whereas interaction
      between PNPase-alpha and enolase was observed in bacteria that synthesize RNase E
      having a scaffold region, immunoprecipitates from cells expressing PNPase-alpha,
      RhlB, and enolase from single-copy chromosomal loci, plus a mutant RNase E
      protein lacking its C-terminal half, showed direct association of PNPase-alpha
      only with RhlB. Using affinity chromatography, we found that PNPase-alpha and
      RhlB form a ribonucleolytically active complex corresponding to the mass
      calculated previously for alpha(3)beta(2) (i.e., 377-380 kDa), whereas no
      association between PNPase-alpha and enolase was detected. Chromosomal deletion
      of the eno gene had no effect on the ability of PNPase to degrade either single-
      or double-stranded RNAs. Collectively, our findings show that direct interaction
      between PNPase-alpha and RhlB occurs physiologically in the absence of the RNase
      E C-terminal region, that enolase association with PNPase-alpha is a consequence
      of the interaction of both proteins with RNase E, and that, contrary to current
      notions, enolase is not the beta-subunit of E. coli PNPase complex.

PMID- 16275924
TI  - Impaired involution of mammary glands in the absence of milk fat globule EGF
      factor 8.
AB  - During the involution of mammary glands, epithelial cells undergo apoptosis and
      are cleared for the next cycle of lactation. The clearance of apoptotic
      epithelial cells is mediated by neighboring epithelial cells and by macrophages
      that migrate into the mammary glands. Here, we report that milk fat globule EGF
      factor 8 (MFG-E8), a secreted glycoprotein that binds to apoptotic cells by
      recognizing phosphatidylserine, was expressed by epithelial cells and macrophages
      in mammary glands and was involved in engulfment of apoptotic cells. A deficiency
      of MFG-E8 caused the accumulation of a large number of milk fat globules (MFGs)
      in the mammary ducts during involution, indicating that the excess MFGs were
      cleared by an MFG-E8-dependent mechanism. The MFG-E8(-/-) mice developed mammary
      duct ectasia with periductal mastitis, and the redevelopment of the mammary gland
      for their second litter was impaired. These results demonstrate that MFG-E8
      mediated phagocytosis of apoptotic epithelial cells and MFGs is important for
      efficient involution of mammary glands.

PMID- 16275925
TI  - High-resolution structure of the catalytic region of MICAL (molecule interacting
      with CasL), a multidomain flavoenzyme-signaling molecule.
AB  - Semaphorins are extracellular cell guidance cues that govern cytoskeletal
      dynamics during neuronal and vascular development. MICAL (molecule interacting
      with CasL) is a multidomain cytosolic protein with a putative flavoprotein
      monooxygenase (MO) region required for semaphorin-plexin repulsive axon guidance.
      Here, we report the 1.45-A resolution crystal structure of the FAD-containing MO
      domain of mouse MICAL-1 (residues 1-489). The topology most closely resembles
      that of the NADPH-dependent flavoenzyme p-hydroxybenzoate hydroxylase (PHBH).
      Comparison of structures before and after reaction with NADPH reveals that, as in
      PHBH, the flavin ring can switch between two discrete positions. In contrast with
      other MOs, this conformational switch is coupled with the opening of a channel to
      the active site, suggestive of a protein substrate. In support of this
      hypothesis, distinctive structural features highlight putative protein-binding
      sites in suitable proximity to the active site entrance. The unusual
      juxtaposition of this N-terminal MO (hydroxylase) activity with the
      characteristics of a multiprotein-binding scaffold exhibited by the C-terminal
      portion of the MICALs represents a unique combination of functionality to mediate
      signaling.

PMID- 16275926
TI  - Structure and activity of the axon guidance protein MICAL.
AB  - During development, neurons are guided to their targets by short- and long-range
      attractive and repulsive cues. MICAL, a large multidomain protein, is required
      for the combined action of semaphorins and plexins in axon guidance. Here, we
      present the structure of the N-terminal region of MICAL (MICAL(fd)) determined by
      x-ray diffraction to 2.0 A resolution. The structure shows that MICAL(fd) is an
      FAD-containing module structurally similar to aromatic hydroxylases and amine
      oxidases. In addition, we present biochemical data that show that MICAL(fd) is a
      flavoenzyme that in the presence of NADPH reduces molecular oxygen to H(2)O(2)
      (K(m,NAPDH) = 222 microM; k(cat) = 77 sec(-1)), a molecule with known signaling
      properties. We propose that the H(2)O(2) produced by this reaction may be one of
      the signaling molecules involved in axon guidance by MICAL.

PMID- 16275928
TI  - Molecular basis for keratoconus: lack of TrkA expression and its transcriptional
      repression by Sp3.
AB  - Keratoconus is the most common corneal dystrophy that leads to severe visual
      impairment. Although the major etiological factors are genetic, the pathogenetic
      mechanism(s) is unknown. No medical treatments exist, and the only therapeutic
      approach is corneal transplantation. Recent data demonstrate the involvement of
      nerve growth factor (NGF) in trophism and corneal wound healing. In this study,
      we investigated alterations in the NGF pathway in keratoconus-affected corneas
      and found a total absence of the NGF-receptor TrkA (TrkA(NGFR)) expression and a
      decreased expression of NGF and p75(NTR). The absence of TrkA(NGFR) expression
      was associated with a strong increase in the Sp3 repressor short isoform(s) and a
      lack of the Sp3 activator long isoform. Sp3 is a bifunctional transcription
      factor that has been reported to stimulate or repress the transcription of
      numerous genes. Indeed, we found that Sp3 short isoform(s) overexpression in cell
      culture results in a down-regulation of TrkA(NGFR) expression. We suggest that an
      imbalance in Sp transcription-factor isoforms may play a role in controlling the
      NGF signaling, thus contributing to the pathogenesis of keratoconus. This
      mechanism for the transcriptional repression of the TrkA(NGFR) gene can provide
      the platform for the development of a therapeutic strategy.

PMID- 16275929
TI  - Gene therapy for progeny of mito-mice carrying pathogenic mtDNA by nuclear
      transplantation.
AB  - Pathogenic mutations in mtDNAs have been shown to be responsible for expression
      of respiration defects and resultant expression of mitochondrial diseases. This
      study directly addressed the issue of gene therapy of mitochondrial diseases by
      using nuclear transplantation of zygotes of transmitochondria mice (mito-mice).
      Mito-mice expressed respiration defects and mitochondrial diseases due to
      accumulation of mtDNA carrying a large-scale deletion (DeltamtDNA). Second polar
      bodies were used as biopsy samples for diagnosis of mtDNA genotypes of mito-mouse
      zygotes. Nuclear transplantation was carried out from mito-mouse zygotes to
      enucleated normal zygotes and was shown to rescue all of the F(0) progeny from
      expression of respiration defects throughout their lives. This procedure should
      be applicable to patients with mitochondrial diseases for preventing their
      children from developing the diseases.

PMID- 16275927
TI  - RNA splicing capability of live neuronal dendrites.
AB  - Dendrites are specialized extensions of the neuronal soma that contain components
      of the cellular machinery involved in RNA and protein metabolism. Several
      dendritically localized proteins are associated with the precursor-mRNA (pre
      mRNA) splicing complex, or spliceosome. Although some spliceosome-related, RNA
      binding proteins are known to subserve separate cytoplasmic functions when moving
      between the nucleus and cytoplasm, little is known about the pre-mRNA splicing
      capacity of intact dendrites. Here, we demonstrate the presence and functionality
      of pre-mRNA-splicing components in dendrites. When isolated dendrites are
      transfected with a chicken delta-crystallin pre-mRNA or luciferase reporter pre
      mRNA, splicing junctions clustered at or near expected splice sites are observed.
      Additionally, in vitro synaptoneurosome experiments show that this subcellular
      fraction contains a similar complement of splicing factors that is capable of
      splicing chicken delta-crystallin pre-mRNA. These observations suggest that pre
      mRNA-splicing factors found in the dendroplasm retain the potential to promote
      pre-mRNA splicing.

PMID- 16275930
TI  - Personality predicts activity in reward and emotional regions associated with
      humor.
AB  - Previous research and theory suggest that two stable personality dimensions,
      extroversion and neuroticism, differentially influence emotional reactivity to a
      variety of pleasurable phenomena. Here, we use event-related functional MRI to
      address the putative neural and behavioral associations between humor
      appreciation and the personality dimensions of introversion-extroversion and
      emotional stability-neuroticism. Our analysis showed extroversion to positively
      correlate with humor-driven blood oxygenation level-dependent signal in discrete
      regions of the right orbital frontal cortex, ventrolateral prefrontal cortex, and
      bilateral temporal cortices. Introversion correlated with increased activation in
      several regions, most prominently the bilateral amygdala. Although neuroticism
      did not positively correlate with any whole-brain activation, emotional stability
      (i.e., the inverse of neuroticism) correlated with increased activation in the
      mesocortical-mesolimbic reward circuitry encompassing the right orbital frontal
      cortex, caudate, and nucleus accumbens. Our findings tie together existing
      neurobiological studies of humor appreciation and are compatible with the notion
      that personality style plays a fundamental role in the neurobiological systems
      subserving humor appreciation.

PMID- 16275933
TI  - Induction redux: once more with taxanes.

PMID- 16275931
TI  - Sex differences in brain activation elicited by humor.
AB  - With recent investigation beginning to reveal the cortical and subcortical
      neuroanatomical correlates of humor appreciation, the present event-related
      functional MRI (fMRI) study was designed to elucidate sex-specific recruitment of
      these humor related networks. Twenty healthy subjects (10 females) underwent fMRI
      scanning while subjectively rating 70 verbal and nonverbal achromatic cartoons as
      funny or unfunny. Data were analyzed by comparing blood oxygenation-level
      dependent signal activation during funny and unfunny stimuli. Males and females
      share an extensive humor-response strategy as indicated by recruitment of similar
      brain regions: both activate the temporal-occipital junction and temporal pole,
      structures implicated in semantic knowledge and juxtaposition, and the inferior
      frontal gyrus, likely to be involved in language processing. Females, however,
      activate the left prefrontal cortex more than males, suggesting a greater degree
      of executive processing and language-based decoding. Females also exhibit greater
      activation of mesolimbic regions, including the nucleus accumbens, implying
      greater reward network response and possibly less reward expectation. These
      results indicate sex-specific differences in neural response to humor with
      implications for sex-based disparities in the integration of cognition and
      emotion.

PMID- 16275934
TI  - Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute
      myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B study.
AB  - PURPOSE: To test the prognostic significance of ETS-related gene (ERG) expression
      in cytogenetically normal primary acute myeloid leukemia (AML). PATIENTS AND
      METHODS: Pretreatment blood samples from 84 cytogenetically normal AML patients
      aged less than 60 years, who were characterized for BAALC expression, FLT3
      internal tandem duplication (ITD), and MLL partial tandem duplication (PTD) and
      uniformly treated on Cancer and Leukemia Group B 9621 protocol, were analyzed for
      ERG expression by real-time reverse transcriptase polymerase chain reaction.
      Patients were divided into quartiles according to ERG levels and were compared
      for clinical outcome. High-density oligonucleotide arrays were used to identify
      genes differentially expressed between high and low ERG expressers. RESULTS: With
      a median follow-up of 5.7 years, patients with the upper 25% of ERG expression
      values had a worse cumulative incidence of relapse (CIR; P < .001) and overall
      survival (OS; P = .011) than the remaining patients. In a multivariable analysis,
      high ERG expression (P < .001) and the presence of MLL PTD (P = .027) predicted
      worse CIR. With regard to OS, an interaction was observed between expression of
      ERG and BAALC (P = .013), with ERG overexpression predicting shorter survival
      only in low BAALC expressers (P = .002). ERG overexpression was an independent
      prognostic factor even when the unfavorable group of FLT3 ITD patients lacking an
      FLT3 wild-type allele was included. High ERG expression was associated with
      upregulation of 112 expressed-sequenced tags and named genes, many of which are
      involved in cell proliferation, differentiation, and apoptosis. CONCLUSION: ERG
      overexpression in AML patients with normal cytogenetics predicts an adverse
      clinical outcome and seems to be associated with a specific molecular signature.

PMID- 16275935
TI  - Early mortality after diagnosis of multiple myeloma: analysis of patients entered
      onto the United kingdom Medical Research Council trials between 1980 and 2002-
      Medical Research Council Adult Leukaemia Working Party.
AB  - PURPOSE: Early mortality in multiple myeloma (MM) is usually attributed to
      combined effects of active disease and comorbid factors. We have studied early
      deaths in a series of large multicenter trials to assess direct causes of death,
      their predictability, and whether current management strategies have reduced
      their frequency. PATIENTS AND METHODS: A total of 3,107 newly diagnosed patients
      entered onto United Kingdom Medical Research Council MM trials from 1980 to 2002
      were studied. Trial files, final clinical summaries, and postmortem reports were
      analyzed. RESULTS: Death within 60 days of trial entry occurred in 299 patients
      (10%). Logistic regression modeling identified beta 2-microglobulin, performance
      status, and age as the most important predictors of early death, but only with
      61% sensitivity and 73% specificity. Forty-five percent of deaths were
      attributable to infection, which was often associated with bone pain
      (particularly thoracic pain) and delay in presenting to medical care. Neutropenia
      was present at diagnosis in only 11 of the 135 deaths from infection. Renal
      failure was present in 28% of early deaths and was linked to light-chain MM,
      hypercalcemia, dehydration, and nonsteroidal anti-inflammatory drugs. There was
      no time related reduction in the percentage or nature of early deaths in 1,550
      patients older than 65 years receiving similar therapy between 1982 and 2002.
      CONCLUSION: A tenth of patients die within 60 days of diagnosis of MM. Infection
      and renal failure are the main direct causes of early mortality, which cannot be
      accurately predicted by presenting prognostic features. All patients should be
      considered at high risk of death during induction therapy.

PMID- 16275936
TI  - High-dose therapy and autologous blood stem-cell transplantation compared with
      conventional treatment in myeloma patients aged 55 to 65 years: long-term results
      of a randomized control trial from the Group Myelome-Autogreffe.
AB  - PURPOSE: To study the impact of high-dose therapy (HDT) with autologous stem-cell
      support in patients with symptomatic multiple myeloma (MM) between the ages of 55
      and 65 years. PATIENTS AND METHODS: One hundred ninety patients between 55 and 65
      years old who had newly diagnosed stage II or III MM were randomly assigned to
      receive either conventional chemotherapy (CCT; ie, monthly courses of a regimen
      of vincristine, melphalan, cyclophosphamide, and prednisone) or HDT and
      autologous blood stem-cell transplantation (using either melphalan alone 200
      mg/m(2) intravenous [IV] or melphalan 140 mg/m(2) IV plus busulfan 16 mg/kg
      orally as pretransplantation cytoreduction). RESULTS: Within a median follow-up
      of 120 months, median event-free survival (EFS) times were 25 and 19 months in
      the HDT and CCT groups, respectively. Median overall survival (OS) time was 47.8
      months in the HDT group compared with 47.6 months in the CCT group. A trend to
      better EFS (P = .07) was observed in favor of HDT, whereas OS curves were not
      statistically different (P = .91). The period of time without symptoms,
      treatment, and treatment toxicity (TwiSTT) was significantly longer for the HDT
      patients than for the CCT patients (P = .03). CONCLUSION: With a median follow-up
      time of approximately 10 years, this randomized trial confirmed a benefit of HDT
      in terms of EFS and TwiSTT but did not provide evidence for superiority of HDT
      over CCT in OS of patients aged 55 to 65 years with symptomatic newly diagnosed
      MM.

PMID- 16275937
TI  - Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin,
      and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally
      advanced head and neck cancer.
AB  - PURPOSE: To compare the antitumor activity and toxicity of the two induction
      chemotherapy treatments of paclitaxel, cisplatin, and fluorouracil (FU; PCF)
      versus standard cisplatin and FU (CF), both followed by chemoradiotherapy (CRT),
      in locally advanced head and neck cancer (HNC). PATIENTS AND METHODS: Eligibility
      criteria included biopsy-proven, previously untreated, stage III or IV locally
      advanced HNC. Patients received either CF (cisplatin 100 mg/m2 on day 1 plus FU
      1000 [corrected] mg/m2 continuous infusion on days 1 through 5) or PCF
      (paclitaxel 175 mg/m2 on day 1, cisplatin 100 mg/m2 on day 2, and FU 500 mg/m2
      continuous infusion on days 2 through 6); both regimens were administered for
      three cycles every 21 days. Patients with complete response (CR) or partial
      response of greater than 80% in primary tumor received additional CRT (cisplatin
      100 mg/m2 on days 1, 22, and 43 plus 70 Gy). RESULTS: A total of 382 eligible
      patients were randomly assigned to CF (n = 193) or PCF (n = 189). The CR rate was
      14% in the CF arm v 33% in the PCF arm (P < .001). Median time to treatment
      failure was 12 months in the CF arm compared with 20 months in the PCF arm (log
      rank test, P = .006; Tarone-Ware, P = .003). PCF patients had a trend to longer
      overall survival (OS; 37 months in CF arm v 43 months in PCF arm; log-rank test,
      P = .06; Tarone-Ware, P = .03). This difference was more evident in patients with
      unresectable disease (OS: 26 months in CF arm v 36 months in PCF arm; log-rank
      test, P = .04; Tarone-Ware, P = .03). CF patients had a higher occurrence of
      grade 2 to 4 mucositis than PCF patients (53% v 16%, respectively; P < .001).
      CONCLUSION: Induction chemotherapy with PCF was better tolerated and resulted in
      a higher CR rate than CF. However, new trials that compare induction chemotherapy
      plus CRT versus CRT alone are needed to better define the role of neoadjuvant
      treatment.

PMID- 16275938
TI  - Validation of a monoclonal antibody-based capture enzyme-linked immunosorbent
      assay for detection of Campylobacter fetus.
AB  - A monoclonal antibody (MAb)-based antigen capture enzyme-linked immunosorbent
      assay (ELISA) was compared with the routine culture methodology for the detection
      of Campylobacter fetus subspecies from bovine and ovine field samples inoculated
      into Clark's transport enrichment medium (TEM). The work was a collaboration
      between two different diagnostic laboratories, one in Canada and the other in
      England. In both labs, TEM samples were incubated for 4 days at 35 degrees C and
      then tested by culture and ELISA. The ELISA consisted of initial screening with
      MAb M1825 against C. fetus subspecies core lipopolysaccharide (LPS). All samples
      positive on ELISA screening were then retested by ELISA with MAb M1825 and MAbs
      M1177, M1183, and M1194, which recognize serotype A- and/or serotype B-specific
      C. fetus subspecies LPS epitopes. The Canadian samples consisted of 1,060
      preputial washings from 529 bulls, of which 18 were positive by both culture and
      ELISA and 1,042 were negative by both methods. The English samples consisted of
      321 tissue specimens, mostly stomach contents and placentas, from 190 aborted
      ovine and bovine fetuses. A total of 262 samples were negative by culture and
      ELISA, 52 samples were positive by culture and ELISA, and 7 samples were culture
      negative but ELISA positive. The results for all 70 culture-positive isolates
      were confirmed by conventional biochemical methods as C. fetus subsp. fetus, with
      39 presumptively identified by the ELISA as serotype A and 30 presumptively
      identified as serotype B and with one sample containing isolates presumptively
      identified as serotype A and serotype B. A receiver operating characteristic
      analysis of the combined ELISA data from both countries resulted in an area under
      the curve of 0.997, with a sensitivity of 100% and a specificity of 99.5%
      relative to the results of culture. The data confirm that this ELISA method can
      be used as an excellent test for the screening of field samples in TEM for the
      presence of C. fetus subspecies.

PMID- 16275939
TI  - Evaluation of a western blot method for the detection of Yersinia antibodies:
      evidence of serological cross-reactivity between Yersinia outer membrane proteins
      and Borrelia burgdorferi.
AB  - Yersinia enterocolitica and Yersinia pseudotuberculosis have been identified as
      causative organisms of reactive arthritis in humans. We evaluated a Western blot
      assay which uses Yersinia outer membrane proteins as antigens for the detection
      of Yersinia antibodies as a replacement for the complement fixation (CF) assay.
      Clinical agreement, sensitivity, and specificity were determined by testing 19
      positive and 21 negative serum samples by the CF assay, Western blot assay, and
      enzyme-linked immunosorbent assay (ELISA). The CF assay and ELISA were compared
      to the Western blot assay, which was the reference method used in this study.
      Sera with antibodies that could potentially cross-react with Yersinia were also
      tested by the Western blot assay. The agreement, sensitivity, and specificity of
      the CF method were 61%, 26%, and 95%, respectively; and those for the ELISA were
      89%, 95%, and 82%, respectively. The prevalences of Yersinia antibodies in 50
      healthy donors were 6% for immunoglobulin G (IgG), 2% for IgA, and 2% for IgM.
      Sera positive for Bartonella henselae, Brucella, Chlamydia pneumoniae, and
      Rickettsia rickettsii antibodies showed cross-reactivity by the Western blot
      assay. The highest cross-reactivity was observed with Borrelia burgdorferi; 5 of
      11 (45%) specimens were cross-reactive by the IgM-specific assay. Overall, the
      Western blot assay performs acceptably and is more sensitive than the CF assay,
      warranting replacement of the CF assay in the laboratory. Due to the evidence of
      cross-reactivity, particularly with B. burgdorferi, which can cause an
      oligoarthritis similar to reactive arthritis, the diagnosis of reactive arthritis
      should be based on clinical findings and complete serologic analysis of the
      potential causative infectious pathogens.

PMID- 16275941
TI  - A strain-specific antigen in Japanese Helicobacter pylori recognized in sera of
      Japanese children.
AB  - An enzyme immuno assay (EIA) test based on Japanese strain-derived high-molecular
      weight cell-associated proteins (JHM-CAP) was evaluated by comparing with a
      previously developed EIA test based on a U.S. strain-derived high-molecular
      weight cell-associated proteins (HM-CAP). Serum samples of 131 Japanese
      asymptomatic children (mean age, 5.5 years; range, 0 to 21 years) were tested
      that include 43 positive and 88 negative children as judged by Helicobacter
      pylori stool antigen test (HpSA test). Both tests showed comparable and reliable
      specificities, but the sensitivity of JHM-CAP EIA, at 93.0%, was much higher than
      that of HM-CAP EIA, at 67.4%. More false-negative results of HM-CAP were obtained
      in children under 10 years of age. Immunoblot analysis revealed that the JHM-CAP
      but not the HM-CAP preparation had a 100-kDa antigen recognized by JHM-CAP
      positive sera. It was concluded that JHM-CAP EIA is highly accurate for the
      serodiagnosis of H. pylori infection in Japanese young children and that the high
      sensitivity of JHM-CAP EIA in contrast to HM-CAP EIA is due to the presence of a
      100-kDa antigen in Japanese strains that may be recognized by the host immune
      system at an early stage of infection.

PMID- 16275940
TI  - Alterations of natural killer cell and T-lymphocyte counts in adults infected
      with human immunodeficiency virus through blood and plasma sold in the past in
      China and in whom infection has progressed slowly over a long period.
AB  - Natural killer (NK) cells, natural killer T (NKT) cells, and T lymphocytes were
      analyzed by using a flow cytometer in 225 human immunodeficiency virus (HIV)
      positive individuals infected through the past sale of blood and plasma without
      receiving antiretroviral therapy in the People's Republic of China. According to
      CD4 T-cell counts these HIV-infected adults were stratified into three groups:
      long-term slow progressors, HIV-infected subjects, and AIDS patients. NK cell
      counts in long-term slow progressors were higher compared to HIV infection and
      AIDS patients (P < 0.05) and lower compared to normal controls (P < 0.05),
      whereas NKT cell counts in slow progressors and the HIV infection group were not
      different from those of normal controls. NK cell counts in HIV-seropositive
      subjects were positively correlated with CD4 T-cell counts (P < 0.05), and NKT
      cell counts were positively correlated with CD4 T-cell and CD8 T-cell counts (P <
      0.05). The CD8 T-cell counts were higher in slow progressors compared to those
      with HIV infection, AIDS patients, and normal controls. These results indicated
      that HIV infection causes alterations of NK cells and T cells in slow
      progressors, HIV-infected subjects, and AIDS patient groups, but no difference
      was found in NKT cell counts and percentages in slow progressors and the HIV
      infected group compared to normal controls.

PMID- 16275942
TI  - Xylitol inhibits inflammatory cytokine expression induced by lipopolysaccharide
      from Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis is one of the suspected periodontopathic bacteria. The
      lipopolysaccharide (LPS) of P. gingivalis is a key factor in the development of
      periodontitis. Inflammatory cytokines play important roles in the gingival tissue
      destruction that is a characteristic of periodontitis. Macrophages are prominent
      at chronic inflammatory sites and are considered to contribute to the
      pathogenesis of periodontitis. Xylitol stands out and is widely believed to
      possess anticaries properties. However, to date, little is known about the effect
      of xylitol on periodontitis. The aim of the present study was to determine tumor
      necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) expression
      when RAW 264.7 cells were stimulated with P. gingivalis LPS (hereafter, LPS
      refers to P. gingivalis LPS unless stated otherwise) and the effect of xylitol on
      the LPS-induced TNF-alpha and IL-1beta expression. The kinetics of TNF-alpha and
      IL-1beta levels in culture supernatant after LPS treatment showed peak values at
      1 h (TNF-alpha) and 2 to 4 h (IL-1beta), respectively. NF-kappaB, a transcription
      factor, was also activated by LPS treatment. These cytokine expressions and NF
      kappaB activation were suppressed by pretreatment with pyrrolidine
      dithiocarbamate (an inhibitor of NF-kappaB). Pretreatment with xylitol inhibited
      LPS-induced TNF-alpha and IL-1beta gene expression and protein synthesis. LPS
      induced mobilization of NF-kappaB was also inhibited by pretreatment with xylitol
      in a dose-dependent manner. Xylitol also showed inhibitory effect on the growth
      of P. gingivalis. Taken together, these findings suggest that xylitol may have
      good clinical effect not only for caries but also for periodontitis by its
      inhibitory effect on the LPS-induced inflammatory cytokine expression.

PMID- 16275943
TI  - Comparison of lipopolysaccharide-binding functions of CD14 and MD-2.
AB  - Prior to being recognized by the cell surface Toll-like receptor 4/MD-2 complex,
      lipopolysaccharide (LPS) in the bacterial outer membrane has to be processed by
      LPS-binding protein and CD14. CD14 forms a complex with monomeric LPS extracted
      by LPS-binding protein and transfers LPS to the cell surface signaling complex.
      In a previous study, we prepared a functional recombinant MD-2 using a bacterial
      expression system. We expressed the recombinant protein in Escherichia coli as a
      fusion protein with thioredoxin and demonstrated specific binding to LPS. In this
      study, we prepared recombinant CD14 fusion proteins using the same approach.
      Specific binding of LPS was demonstrated with a recombinant protein containing
      151 amino-terminal residues. The region contained a hydrophilic region and the
      first three leucine-rich repeats (LRRs). The LRRs appeared to contribute to the
      binding because removal of the region resulted in a reduction in the binding
      function. LPS binding to the recombinant MD-2 was resistant to detergents. On the
      other hand, the binding to CD14 was prevented in the presence of low
      concentrations of detergents. In the case of human MD-2, the secondary myristoyl
      chain of LPS added by LpxM was required for the binding. A nonpathogenic penta
      acyl LPS mutant lacking the myristoyl chain did not bind to MD-2 but did so
      normally to CD14. The broader LPS-binding spectrum of CD14 may allow recognition
      of multiple pathogens, and the lower affinity for LPS binding of CD14 allows
      transmission of captured materials to MD-2.

PMID- 16275944
TI  - Persistent replication of human immunodeficiency virus type 1 despite treatment
      of pulmonary tuberculosis in dually infected subjects.
AB  - Tuberculosis (TB) is the most common life-threatening infection in human
      immunodeficiency virus (HIV)-infected persons and frequently occurs before the
      onset of severe immunodeficiency. Development of TB is associated with increased
      HIV type 1 (HIV-1) viral load, a fall in CD4 lymphocyte counts, and increased
      mortality. The aim of this study was to examine how treatment of pulmonary TB
      affected HIV-1 activity in HIV-1/TB-coinfected subjects with CD4 cell counts of
      >100 cells/mul. HIV-1/TB-coinfected subjects were recruited in Kampala, Uganda,
      and were monitored over time. Based upon a significant (0.5 log10 copies/ml)
      decrease in viral load by the end of treatment, two patient groups could be
      distinguished. Responders (n = 17) had more rapid resolution of anemia and
      pulmonary lesions on chest radiography during TB treatment. This group had a
      significant increase in viral load to levels not different from those at baseline
      6 months after completion of TB treatment. HIV-1 viral load in nonresponders (n =
      10) with TB treatment increased and at the 6 month follow-up was significantly
      higher than that at the time of diagnosis of TB. Compared to baseline levels,
      serum markers of macrophage activation including soluble CD14 decreased
      significantly by the end of TB treatment in responders but not in nonresponders.
      These data further define the impact of pulmonary TB on HIV-1 disease. HIV-1
      replication during dual HIV-1/TB infection is not amenable to virologic control
      by treatment of TB alone. Concurrent institution of highly active antiretroviral
      treatment needs to be evaluated in patients dually infected with pulmonary TB and
      HIV-1.

PMID- 16275945
TI  - Immunological markers of the R4 protein of Streptococcus agalactiae.
AB  - This study focuses on immunological markers of R4, an important Streptococcus
      group B (GBS) protein. The results obtained by using rabbit antisera and purified
      proteins for antigens in enzyme-linked immunosorbent assay-based experiments
      provided evidence that R4 possesses two antigenic determinants. One of the
      determinants is shared with the alpha-like protein 3 (Alp3) of GBS, was named
      R4/Alp3 common, and was expressed by GBS, which possessed the Alp3-encoding gene
      alp3 or the R4-encoding gene rib. The other antigenic determinant was detected
      only in rib-positive GBS organisms and was named R4 specific. This determinant
      probably is an immunological marker unique to the R4 protein. Neither of the
      antigenic R4 determinants showed serological cross-reactivity with the GBS
      proteins Calpha, Cbeta, and R3 or with alpha-like protein 2. Of 60 clinical
      serotype III GBS strains, 56 (93%) isolates possessed the rib gene and 50 (89%)
      of the rib-positive isolates expressed levels of R4 detectable by antibody-based
      tests, consistent with R4 expression failure or low-level expression in
      approximately 10% of rib-positive GBS. alp3 was not detected in type III GBS but
      was possessed by six of eight type V strains and six of six type VIII strains.
      All alp3-positive strains were recognized by the R4/Alp3 common antibodies, but
      none of them were recognized by the R4-specific antibodies. NCTC 9828, a
      reference strain for R3 and R4, expressed the determinant R4/Alp3 common but not
      R4 specific. A monoclonal R4 antibody, previously considered to be R4 specific
      and used in GBS serotyping, targeted R4/Alp3 common and is thus not R4 specific.
      The results show that failure to discriminate between R4 specific and R4/Alp3
      common by antisera designed for GBS serotyping can result in the false
      identification of Alp3 as R4 or vice versa, whereas anti-R4 antibodies targeting
      only the determinant R4 specific will detect only R4. Both R4 and Alp3 need
      further evaluation with respect to the immunobiological function of each distinct
      antigenic determinant, for instance, with regard to their potential as GBS
      vaccine components.

PMID- 16275947
TI  - Serological responses in patients with severe acute respiratory syndrome
      coronavirus infection and cross-reactivity with human coronaviruses 229E, OC43,
      and NL63.
AB  - The serological response profile of severe acute respiratory syndrome (SARS)
      coronavirus (CoV) infection was defined by neutralization tests and subclass
      specific immunofluorescent (IF) tests using serial sera from 20 patients. SARS
      CoV total immunoglobulin (Ig) (IgG, IgA, and IgM [IgGAM]) was the first antibody
      to be detectable. There was no difference in time to seroconversion between the
      patients who survived (n = 14) and those who died (n = 6). Although SARS CoV IgM
      was still detectable by IF tests with 8 of 11 patients at 7 months postinfection,
      the geometric mean titers dropped from 282 at 1 month postinfection to 19 at 7
      months (P = 0.001). In contrast, neutralizing antibody and SARS CoV IgGAM and IgG
      antibody titers remained stable over this period. The SARS CoV antibody response
      was sometimes associated with an increase in preexisting IF IgG antibody titers
      for human coronaviruses OC43, 229E, and NL63. There was no change in IF IgG titer
      for virus capsid antigen from the herpesvirus that was used as an unrelated
      control, Epstein-Barr virus. In contrast, patients who had OC43 infections, and
      probably also 229E infections, without prior exposure to SARS CoV had increases
      of antibodies specific for the infecting virus but not for SARS CoV. There is a
      need for awareness of cross-reactive antibody responses between coronaviruses
      when interpreting IF serology.

PMID- 16275946
TI  - Selected RD1 peptides for active tuberculosis diagnosis: comparison of a gamma
      interferon whole-blood enzyme-linked immunosorbent assay and an enzyme-linked
      immunospot assay.
AB  - We recently set up a gamma interferon (IFN-gamma) enzyme-linked immunospot assay
      (ELISPOT), using selected early secreted antigenic target 6 (ESAT-6) peptides,
      that appears specific for active tuberculosis (A-TB). However, ELISPOT is
      difficult to automate. Thus, the objective of this study was to determine if the
      same selected peptides may be used in a technique more suitable for routine work
      in clinical laboratories, such as whole-blood enzyme-linked immunosorbent assay
      (WBE). For this purpose, 27 patients with A-TB and 41 control patients were
      enrolled. Our WBE, using the already described selected peptides from ESAT-6 plus
      three new ones from culture filtrate protein 10, was performed, and data were
      compared with those obtained by ELISPOT. Using our selected peptides, IFN-gamma
      production, evaluated by both WBE and ELISPOT, was significantly higher in
      patients with A-TB than in controls (P < 0.0001). Statistical analysis showed a
      good correlation between the results obtained by WBE and ELISPOT (r = 0.80, P <
      0.001). To substantiate our data, we compared our WBE results with those obtained
      by QuantiFERON-TB Gold, a whole-blood assay based on region of difference 1 (RD1)
      overlapping peptides approved for TB infection diagnosis. We observed a slightly
      higher sensitivity with QuantiFERON-TB Gold than with our WBE (89% versus 81%);
      however, our test provided a better specificity result (90% versus 68%). In
      conclusion, results obtained by WBE based on selected RD1 peptides significantly
      correlate with those generated by ELISPOT. Moreover, our assay appears more
      specific for A-TB diagnosis than QuantiFERON-TB Gold, and thus it may represent a
      complementary tool for A-TB diagnosis for routine use in clinical laboratories.

PMID- 16275949
TI  - Serological markers (anti-Saccharomyces cerevisiae mannan antibodies and
      antineutrophil cytoplasmic antibodies) in inflammatory bowel disease: diagnostic
      utility and phenotypic correlation.
AB  - We have evaluated the utility of antineutrophil cytoplasmic antibodies and anti
      Saccharomyces cerevisiae mannan antibodies for distinguishing Crohn's disease
      from ulcerative colitis and other diarrheal illnesses by evaluating sera from 396
      patients. Sensitivity, specificity, and phenotypic correlations were
      investigated. The implications of our findings for implementing these tests in
      routine clinical testing are discussed.

PMID- 16275948
TI  - Comparison of galactomannan detection, PCR-enzyme-linked immunosorbent assay, and
      real-time PCR for diagnosis of invasive aspergillosis in a neutropenic rat model
      and effect of caspofungin acetate.
AB  - The performance of different in vitro diagnostic tests for the diagnosis of
      invasive aspergillosis (IA) was investigated in a transiently neutropenic rat
      model. Rats were immunosuppressed with cyclophosphamide and then inoculated
      intravenously with 1.5 x 10(4) CFU Aspergillus fumigatus spores. Animals were
      then either treated with caspofungin acetate, 1 mg/kg/day for 7 days, or not
      treated. PCR-enzyme-linked immunosorbent assay (ELISA), real-time PCR, and
      galactomannan (GM) detection were performed on postmortem blood samples, along
      with culture of liver, lung, and kidney homogenate. Caspofungin-treated animals
      showed a decrease in residual tissue burden of A. fumigatus from organ homogenate
      compared to untreated animals (P < 0.002). PCR-ELISA returned positive results
      for 11/17 animals treated with antifungal agents and for 10/17 untreated animals.
      Galactomannan was positive in 8/17 caspofungin-treated animals and 4/17 untreated
      animals. Real-time PCR was positive in 2/17 treated and 3/17 untreated animals.
      This study demonstrates that PCR-ELISA is a more sensitive test than either GM
      detection (P = 0.052) or real-time PCR (P < 0.01) for diagnosis of IA but that
      any of the three tests may return false-negative results in cases of
      histologically proven disease. Galactomannan indices from animals treated with
      antifungal agents showed a trend (P = 0.1) towards higher levels than those of
      untreated animals, but no effect was observed with PCR-ELISA indices (P = 0.29).
      GM detection, as previously described, may be enhanced by the administration of
      caspofungin, but PCR-ELISA appears not to be affected in the same way. We
      conclude that PCR-ELISA is a more sensitive and reliable method for laboratory
      diagnosis of IA.

PMID- 16275950
TI  - Immunoglobulin G kappa [IgG kappa] and IgG lambda paraproteinemia in a child with
      AIDS and response to highly active antiretroviral therapy.
AB  - We report an 8-year-old boy with AIDS, extremely elevated serum immunoglobulin G
      (IgG) concentration and IgG kappa [IgG(kappa)] and IgG lambda [IgG(lambda)]
      paraproteinemia. This paraproteinemia partially responded to highly active
      antiretroviral therapy. This case emphasizes the importance of controlling B-cell
      activation.

PMID- 16275951
TI  - Evaluation of the PANBIO Brucella immunoglobulin G (IgG) and IgM enzyme-linked
      immunosorbent assays for diagnosis of human brucellosis.
AB  - PANBIO Brucella immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays
      (ELISAs) were assessed against Brucella standard agglutination tube and Coombs
      tests. The sensitivities of ELISA IgG and IgM were 91% and 100%, respectively,
      while the specificity was 100% for both. These ELISAs are simple, rapid, and
      reliable for the diagnosis of human brucellosis.

PMID- 16275952
TI  - Isolation and characterization of the promoter and partial enhancer region of the
      porcine inter-alpha-trypsin inhibitor heavy chain 4 gene.
AB  - A porcine genomic library was screened for clones containing the promoter of the
      major acute-phase protein in pigs, inter-alpha-trypsin heavy chain 4 (ITIH4).
      Following isolation of the promoter, a functional analysis was performed with
      Hep3B cells. The promoter was induced by interleukin-6 (IL-6) but not by IL
      1beta. However, IL-1beta was shown to inhibit the IL-6-induced activation of the
      porcine ITIH4 promoter.

PMID- 16275953
TI  - Immunogenicity of fowlpox virus expressing the avian influenza virus H5 gene
      (TROVAC AIV-H5) in cats.
AB  - Vaccination of cats with fowlpox virus expressing the avian influenza (AI) virus
      H5 hemagglutinin gene (TROVAC AI) resulted in detectable hemagglutination
      inhibition (HI) antibody responses to the homologous A/Turkey/Ireland/1378/83
      (H5N8) (A/tky/Ire/83) AI virus antigen. The HI antibody responses to heterologous
      A/Chicken/Indonesia/7/03 (H5N1) (A/ck/Indonesia/03) AI virus antigen were also
      detected in all vaccinated cats, but only after booster vaccinations. The vaccine
      described in this study and other poxvirus-vectored vaccines may be of value for
      the prophylaxis of AI virus-associated morbidity and mortality in mammals.

PMID- 16275954
TI  - Detection of Babesia canis rossi, B. canis vogeli, and Hepatozoon canis in dogs
      in a village of eastern Sudan by using a screening PCR and sequencing
      methodologies.
AB  - Babesia and Hepatozoon infections of dogs in a village of eastern Sudan were
      analyzed by using a single PCR and sequencing. Among 78 dogs, 5 were infected
      with Babesia canis rossi and 2 others were infected with B. canis vogeli. Thirty
      three dogs were positive for Hepatozoon. Hepatozoon canis was detected by
      sequence analysis.

PMID- 16275955
TI  - Effects of porcine circovirus type 2 (PCV2) maternal antibodies on experimental
      infection of piglets with PCV2.
AB  - To determine the effects of porcine circovirus type 2 (PCV2) maternal antibodies
      on and response to experimental PCV2 infection, 24 piglets were divided into four
      groups on the basis of the enzyme-linked immunosorbent assay titers of PCV2
      maternal antibodies: group A (n = 6; sample/positive [S/P] ratio, <0.2), group B
      (n = 5; S/P ratio, >0.2 to <0.5), and groups C (n = 8) and D (n = 5) (S/P ratio,
      >0.5). Piglets in groups A, B, and C were inoculated with PCV2 at day 0 and
      challenged with PCV2 at day 42. Group D piglets were not exposed to PCV2 at day 0
      but were challenged at day 42. Before challenge, seroconversion to PCV2
      antibodies occurred in five of six group A piglets, and the antibody level rose
      above the cutoff level in one of five group B piglets. Viremia was detected in
      five of six, four of five, and two of eight pigs in groups A, B, and C,
      respectively. After challenge, PCV2 DNA was detectable from 7 to 21 days
      postchallenge in the sera from six of six, four of five, three of eight, and five
      of five pigs in groups A, B, C, and D, respectively. The results indicated that
      protection against PCV2 infection conferred by maternal antibodies is titer
      dependent: higher titers are generally protective, but low titers are not.

PMID- 16275958
TI  - Medical schools tackle conflict of interest.

PMID- 16275959
TI  - MPs call for removal of Health Canada's breast-implant panel members.

PMID- 16275960
TI  - Canada resists banning flame retardant.

PMID- 16275961
TI  - Dire needs post earthquake.

PMID- 16275962
TI  - Progress in the prevention of pneumococcal infection.

PMID- 16275963
TI  - Applying the 2005 Canadian Hypertension Education Program recommendations: 5.
      Therapy for patients with hypertension and diabetes mellitus.

PMID- 16275964
TI  - Chewing the fat on trans fats.

PMID- 16275956
TI  - Canadian Society of Transplantation: consensus guidelines on eligibility for
      kidney transplantation.

PMID- 16275965
TI  - Do ASA and NSAIDs reduce the risk of colorectal cancer?

PMID- 16275966
TI  - [Anticholinergic intoxication].

PMID- 16275967
TI  - Nonsurgical management of partial adhesive small-bowel obstruction with oral
      therapy: a randomized controlled trial.
AB  - BACKGROUND: Patients with partial adhesive small-bowel obstruction are usually
      managed conservatively, receiving intravenous hydration and nothing by mouth.
      Previous studies have suggested that this approach is associated with longer
      hospital stays and an increased risk of delayed surgery. We conducted a
      randomized controlled trial to see if combining standard conservative treatment
      with oral administration of a laxative, a digestant and a defoaming agent would
      reduce the frequency of subsequent surgical intervention and reduce the length of
      hospital stay. METHODS: We identified 144 consecutive patients admitted between
      February 2000 and July 2001 with adhesive partial small-bowel obstruction and
      randomly assigned 128 who met the inclusion criteria to either the control group
      (intravenous hydration, nasogastric-tube decompression and nothing by mouth) or
      the intervention group (intravenous hydration, nasogastric-tube decompression and
      oral therapy with magnesium oxide, Lactobacillus acidophilus and simethicone).
      The primary outcome measures were the number of patients whose obstruction was
      successfully treated without surgery and the length of hospital stay. We also
      monitored rates of complications and recurring obstructions. RESULTS: Of the 128
      patients, 63 were in the control group and 65 in the intervention group; the mean
      ages were 54.4 (standard deviation [SD] 15.9) years and 53.9 (SD 16.3) years
      respectively. Most of the patients were male. More patients in the intervention
      group than in the control group had successful treatment without surgery (59
      [91%] v. 48 [76%], p = 0.03; relative risk 1.19, 95% confidence interval 1.03
      1.40). The mean hospital stay was significantly longer among patients in the
      control group than among those in the intervention group (4.2 [SD 2.7] v. 1.0 [SD
      0.7] days, p < 0.001). The complication and recurrence rates did not differ
      significantly between the 2 groups. INTERPRETATION: Oral therapy with magnesium
      oxide, L. acidophilus and simethicone was effective in hastening the resolution
      of conservatively treated partial adhesive small-bowel obstruction and shortening
      the hospital stay.

PMID- 16275969
TI  - Canadian Society of Transplantation consensus guidelines on eligibility for
      kidney transplantation.

PMID- 16275968
TI  - Socioeconomic status and the utilization of diagnostic imaging in an urban
      setting.
AB  - BACKGROUND: In publicly funded health care systems, the utilization of health
      care services should be equitable, irrespective of socioeconomic status (SES).
      Although the association between SES and health care utilization has been
      examined in Canada relative to surgical, cardiac and preventive health care
      services, no published studies have specifically explored the association between
      SES and diagnostic imaging. METHODS: We examined over 300,000 diagnostic imaging
      claims made in the Winnipeg Regional Health Authority between Apr. 1, 2001, and
      Mar. 31, 2002. Using patient postal codes, we assigned SES on the basis of
      average household incomes in Canada's 1996 census. Using multiple regression, we
      examined the association between income quintile, patient age group (< or =16, 17
      64, > or = 65 years), patient morbidity level according to the Johns Hopkins
      University Adjusted Clinical Group method (high, moderate, low), and imaging
      modality (general radiology, vascular, computed tomography, magnetic resonance,
      and general and obstetric ultrasound). RESULTS: Relative rates (RR) of diagnostic
      imaging utilization (highest v. lowest income quintile) were significantly
      increased in pediatric and adult patient groups at all morbidity levels receiving
      general radiology (highest RR 2.47, 95% confidence interval [CI] 2.07-2.93);
      pediatric and adult patient groups at high and low morbidity levels and elderly
      patient groups at low morbidity levels receiving general ultrasound (highest RR
      2.26, 95% CI 1.20-4.26); pediatric and adult patient groups at all morbidity
      levels and elderly patients at high and moderate morbidity levels receiving
      magnetic resonance imaging (highest RR 2.51, 95% CI 1.78- 3.52); and adult
      patient groups at all morbidity levels receiving computed tomography (highest RR
      1.46, 95% CI 1.35- 1.59). A lower RR of diagnostic imaging utilization in the
      highest income quintile was found only among patients receiving obstetric
      ultrasound (RR 0.80, 95% CI 0.73-0.87). No significant associations were found
      among elderly patients receiving general radiology or computed tomography or
      adult patients receiving vascular imaging. INTERPRETATION: We found a pattern of
      increased diagnostic imaging utilization in patient groups with a higher SES.
      Further research is needed to better understand the nature of this finding and
      how it contributes to health outcomes.

PMID- 16275970
TI  - Of genomics and public health: Building public "goods"?

PMID- 16275973
TI  - Using antidepressants during pregnancy.

PMID- 16275974
TI  - Predicting cardiac outcomes.

PMID- 16275975
TI  - A positive prognosis.

PMID- 16275976
TI  - Questioning the benefits of statins.

PMID- 16275971
TI  - Troponin: the biomarker of choice for the detection of cardiac injury.
AB  - It has been known for 50 years that transaminase activity increases in patients
      with acute myocardial infarction. With the development of creatine kinase (CK),
      biomarkers of cardiac injury began to take a major role in the diagnosis and
      management of patients with acute cardiovascular disease. In 2000 the European
      Society of Cardiology and the American College of Cardiology recognized the
      pivotal role of biomarkers and made elevations in their levels the "cornerstone"
      of diagnosis of acute myocardial infarction. At that time, they also acknowledged
      that cardiac troponin I and T had supplanted CK-MB as the analytes of choice for
      diagnosis. In this review, we discuss the science underlying the use of troponin
      biomarkers, how to interpret troponin values properly and how to apply these
      measurements to patients who present with possible cardiovascular disease.

PMID- 16275979
TI  - Questioning the benefits of statins.

PMID- 16275980
TI  - Editorial: X versus X--the fight for function within the female cell and the
      development of autoimmune thyroid disease.

PMID- 16275981
TI  - Editorial: germline variants within RET: clinical utility or scientific playtoy?

PMID- 16275982
TI  - Letter re: 25-OH-vitamin D assays.

PMID- 16275983
TI  - Letter re: melanin-concentrating hormone and energy balance.

PMID- 16275984
TI  - Letter re: sex hormones and metabolic syndrome in aging men.

PMID- 16275985
TI  - Genes to vaccines for immunotherapy: how the molecular biology revolution has
      influenced cancer immunology.
AB  - Recent advances in our understanding of the complex signaling pathways involved
      in immune system regulation, along with analyses of genetic differences between
      tumors and their normal cellular counterparts, have accelerated development of
      immune-based strategies for cancer treatment and prevention. More clinically
      relevant animal models have shown that successful immune-based strategies will
      require the integration of interventions that target specific tumor antigens with
      regulators of the antitumor immune response. Immunotherapy for cancer is at a
      critical crossroad, as therapeutics designed to target cancer-associated antigens
      and regulatory signaling molecules enter clinical trials. We outline here a
      paradigm for early-stage clinical development of immunotherapy combinations that
      use vaccines to drive tumor antigen-specific responses while simultaneously
      targeting immune regulatory pathways.

PMID- 16275986
TI  - PRL phosphatases as potential molecular targets in cancer.
AB  - The phosphatase of regenerating liver (PRL) family of phosphatases, consisting of
      PRL-1, PRL-2, and PRL-3, represents an intriguing group of proteins being
      validated as biomarkers and therapeutic targets in cancer. Individual PRLs are
      overexpressed in a variety of cancer cell lines and tissues when compared with
      their normal counterparts. More importantly, several recent studies have shown
      that PRL-3 is expressed at higher levels and at a greater frequency in colorectal
      cancer metastases compared with primary colorectal tumors and normal colon
      tissue. Ectopic expression of PRLs in nontumorigenic cells can influence
      proliferation and the migratory and invasive properties of cells, while knockdown
      of endogenous PRL-3 or PRL-1 in cancerous cells using small interfering RNA can
      abrogate cell motility and ability to metastasize in a mouse model. However, the
      exact biological function and cellular substrates of the PRLs remain unclear.
      This review will discuss what is known about the PRLs, what makes the PRLs
      possible attractive targets for therapeutic intervention, and the possible future
      directions in PRL biology and inhibitor identification.

PMID- 16275987
TI  - Imaging androgen receptor function during flutamide treatment in the LAPC9
      xenograft model.
AB  - The current understanding of the response of androgen receptor to pharmacologic
      inhibitors in prostate cancer is derived primarily from serum prostate-specific
      antigen (PSA) levels. In this study, we test whether a novel androgen receptor
      specific molecular imaging system is able to detect the action of the
      antiandrogen flutamide on androgen receptor function in xenograft models of
      prostate cancer. Adenoviruses bearing an optical imaging cassette containing an
      androgen receptor-responsive two-step transcriptional amplification system were
      injected into androgen-dependent and hormone-refractory tumors of animals
      undergoing systemic time-controlled release of the antiandrogen flutamide.
      Imaging of tumors with a cooled charge-coupled device camera revealed that the
      response of AdTSTA to flutamide is more sensitive and robust than serum PSA
      measurements. Flutamide inhibits the androgen signaling pathway in androgen
      dependent but not refractory tumors. Analysis of androgen receptor and RNA
      polymerase II binding to the endogenous PSA gene by chromatin immunoprecipitation
      revealed that flutamide treatment and androgen withdrawal have different
      molecular mechanisms. The application of imaging technology to study animal
      models of cancer provides mechanistic insight into antiandrogen targeting of
      androgen receptor during disease progression.

PMID- 16275988
TI  - Biological and molecular properties of a new alpha(v)beta3/alpha(v)beta5 integrin
      antagonist.
AB  - The aim of the present study was to identify specific alpha(v)beta3/alpha(v)beta5
      integrin antagonists active on tumor-induced angiogenesis. To this purpose, in
      vitro integrin-binding assays were used to screen a library of conformationally
      constrained bicyclic lactam Arg-Gly-Asp-containing pseudopeptides. The results
      identified ST1646 as a high-affinity specific ligand for alpha(v)beta3 and
      alpha(v)beta5 integrins with negligible interacting with alpha5beta1 integrin. In
      all the assays, ST1646 was equipotent to or more potent than the well
      characterized integrin antagonists c(RGDfV) and cyclo(Arg-Gly-Asp-d-Phe-[NMe]Val)
      (EMD121974). In the chorioallantoic membrane assay, topical administration of
      ST1646 was able to prevent the angiogenic responses elicited by recombinant
      fibroblast growth factor-2 or vascular endothelial growth factor. In addition,
      systemic administration of ST1646 in mice exerted a significant antiangiogenic
      activity on neovascularization triggered by mammary carcinoma MDA-MB435 cells
      implanted s.c. in a dorsal air sac via a (Millipore Filter Corporation, Bedford,
      MA) chamber. Moreover, ST1646 delivery via an osmotic pump inhibited the growth
      and vascularization of tumor xenografts originating from the injection of
      alpha(v)beta3/alpha(v)beta5-expressing human ovarian carcinoma cells in nude
      mice. In agreement with the biochemical and pharmacologic studies, Monte
      Carlo/Stochastic Dynamics simulation showed that the bicyclic scaffold in ST1646
      forced the compound to assume a preferred conformation superimposable to the X
      ray conformation of alpha(v)beta3-bound EMD121974. Accordingly, computer-docking
      studies indicated that the ST1646-alpha(v)beta3 integrin complex maintains the
      ligand-receptor distances and interactions observed in the crystalline EMD121974
      alpha(v)beta3 integrin complex. Taken together, these observations indicate that
      ST1646 represents a dual alpha(v)beta3/alpha(v)beta5 integrin antagonist with
      interesting biochemical and biological features to be tested in cancer therapy.

PMID- 16275989
TI  - Targeting integrin-linked kinase inhibits Akt signaling pathways and decreases
      tumor progression of human glioblastoma.
AB  - The phosphatidylinositol 3-kinase pathway is an important regulator of a wide
      spectrum of tumor-related biological processes, including cell proliferation,
      survival, and motility, as well as neovascularization. Protein kinase B/Akt is
      activated in a complex manner through the phosphorylation of protein kinase B/Akt
      on Thr308 and Ser473. Although protein-dependent kinase-1 has been shown to
      phosphorylate Akt at Thr308, it is not clear whether there is a distinct kinase
      that exclusively phosphorylates Akt at Ser473. A possible candidate is integrin
      linked kinase (ILK), which has been shown to phosphorylate Akt at Ser473 in
      vitro. ILK is a multidomain focal adhesion protein that is believed to be
      involved in signal transmission from integrin and growth factor receptors.
      Further, ILK is implicated in the regulation of anchorage-dependent cell
      growth/survival, cell cycle progression, invasion and migration, and tumor
      angiogenesis. In this study, we tested the hypothesis that ILK inhibition would
      inhibit these processes in gliomas in which it is constitutively expressed. We
      found that a newly developed small-molecule compound (QLT0267) effectively
      inhibited signaling through the ILK/Akt cascade in glioma cells by blocking the
      phosphorylation of Akt and downstream targets, including mammalian target of
      rapamycin and glycogen synthase kinase-3beta. Treatment of glioma cells with 12.5
      micromol/L QLT0267 inhibited cell growth by 50% at 48 hours. An anchorage
      dependent cell growth assay confirmed the cell growth-inhibitory effect of
      QLT0267. Further, the decrease in cell growth was associated with a dramatic
      accumulation of cells in the G2-M phase of the cell cycle. Although the cell
      growth-inhibitory effects of the ILK inhibitor were achieved only at a high
      concentration, the QLT0267 was able to reduce cellular invasion and angiogenesis
      at much lower concentrations as shown by in vitro invasion assays and vascular
      endothelial growth factor secretion. Thus, blocking the ILK/Akt pathway is a
      potential strategy for molecular targeted therapy for gliomas.

PMID- 16275990
TI  - A novel antisense oligonucleotide inhibiting several antiapoptotic Bcl-2 family
      members induces apoptosis and enhances chemosensitivity in androgen-independent
      human prostate cancer PC3 cells.
AB  - Bcl-2 and Bcl-xL are associated with treatment resistance and progression in many
      cancers, including prostate cancer. The objective of this study was to determine
      whether a novel bispecific antisense oligonucleotide targeting both Bcl-2 and Bcl
      xL induces apoptosis and enhances chemosensitivity in androgen-independent PC3
      prostate cancer cells. An antisense oligonucleotide with complete sequence
      identity to Bcl-2 and three-base mismatches to Bcl-xL selected from five
      antisense oligonucleotides targeting various regions with high homology between
      Bcl-2 and Bcl-xL was found to be the most potent inhibitor of both Bcl-2 and Bcl
      xL expression in PC3 cells. This selected Bcl-2/Bcl-xL bispecific antisense
      oligonucleotide reduced mRNA and protein levels in a dose-dependent manner,
      reducing Bcl-2 and Bcl-xL protein levels to 12% and 19%, respectively.
      Interestingly, Mcl-1 was down-regulated as well, although levels of Bax, Bad, or
      Bak were not altered after treatment with this bispecific antisense
      oligonucleotide. Indirect down-regulation of inhibitor of apoptosis (IAP) family,
      including XIAP, cIAP-1 and cIAP-2, via second mitochondria-derived activator of
      caspases was also observed after bispecific antisense oligonucleotide treatment.
      Executioner caspase-3, caspase-6, and caspase-7 were shown to be involved in
      apoptosis induced by bispecific antisense oligonucleotide. This Bcl-2/Bcl-xL
      bispecific antisense oligonucleotide also enhanced paclitaxel chemosensitivity in
      PC3 cells, reducing the IC50 of paclitaxel by >90%. These findings illustrate
      that combined suppression of antiapoptotic Bcl-2 family members using this
      antisense oligonucleotide could be an attractive strategy for inhibiting cancer
      progression through alteration of the apoptotic rheostat in androgen-independent
      prostate cancer.

PMID- 16275991
TI  - Antiproliferative activity of angiotensin II receptor blocker through cross-talk
      between stromal and epithelial prostate cancer cells.
AB  - We showed previously that angiotensin II activated the proliferation of prostate
      cancer cells and that angiotensin II receptor blockers (ARB) could inhibit it.
      Here, we investigated whether angiotensin II exerts mitogenic effects on the
      cross-talk between stromal and cancer cells and whether an ARB can inhibit tumor
      growth through actions on stromal cells. Cell proliferation and interleukin-6
      secretion of prostate stromal PrSC cells stimulated with angiotensin II, tumor
      necrosis factor-alpha, or epidermal growth factor were examined in the absence
      and presence of ARB. We examined the effect of ARB on mitogen-activated protein
      kinase (MAPK) phosphorylation of PrSC and PC-3 cells treated with conditioned
      medium of PrSC cells and determined the effect of ARB on tumor growth induced by
      paracrine factors from PrSC cells. Angiotensin II activated the cell
      proliferation and interleukin-6 secretion of PrSC cells, and ARB inhibited it.
      Angiotensin II, tumor necrosis factor-alpha, or epidermal growth factor induced
      MAPK phosphorylation in PrSC cells, and this phosphorylation was inhibited by
      ARB. Conditioned medium of PrSC cells with angiotensin II activated MAPK
      phosphorylation in PC-3 cells, and ARB-treated conditioned medium of PrSC cells
      inhibited it. The tumor growth and angiogenesis of a mixture of PC-3 with PrSC
      were inhibited by ARB administration, whereas those of PC-3 xenografts were not
      inhibited. ARB exerted an antiproliferative effect on prostate cancer through
      paracrine factors from stromal cells. Because prostate stromal cells are thought
      to be involved in the initiation and development of prostate cancer, the present
      data suggest the possibility that ARBs are a novel therapeutic class of agents
      for prostate cancer.

PMID- 16275992
TI  - Gene therapy with E2F-1 up-regulates the protein kinase PKR and inhibits growth
      of leiomyosarcoma in vivo.
AB  - Overexpression of the transcription factor E2F-1 induces apoptosis in a variety
      of carcinoma cells and inactivates murine double minute protein 2, a factor
      associated with poor prognosis in soft tissue sarcomas. We have shown previously
      that the double-stranded RNA-activated protein kinase PKR plays an important role
      in mediating this apoptotic response in carcinoma cells to E2F-1. We sought to
      evaluate the potential of E2F-1 gene therapy in soft tissue sarcomas and to study
      the involvement of PKR in the response to E2F-1 overexpression in mesenchymal
      cells. A replication-deficient adenovirus carrying the E2F-1 gene (Ad5E2F) was
      used to induce E2F-1 overexpression in the p53 mutated leiomyosarcoma cell line,
      SKLMS-1. Western blot analysis confirmed E2F-1 overexpression and up-regulation
      of the antiapoptotic factor Bcl-2 48 hours following infection with Ad5E2F.
      Apoptosis in Ad5E2F-treated cells was confirmed by fluorescence-activated cell
      sorting analysis and by poly(ADP-ribose) polymerase cleavage and DNA
      fragmentation assays. Vector-dependent up-regulation of PKR correlated with the
      amount of Ad5E2F-induced apoptosis. In vivo treatment of SKLMS-1 tumor-bearing
      BALB/c mice with intratumoral injections of Ad5E2F at a dose of 2 x 10(10) viral
      particles resulted in significant inhibition in tumor growth compared with
      control-treated animals (P < 0.016). Complete disappearance of all tumors was
      seen in two of seven mice in the Ad5E2F-treated animals. Immunohistochemical
      analysis of tumor specimens showed overexpression of E2F-1 and up-regulation of
      PKR in Ad5E2F-treated tumors. These findings show that adenovirus-mediated
      overexpression of E2F-1 results in up-regulation of PKR and significant growth
      suppression of leiomyosarcomas in vivo. Taken together, these data suggest that
      E2F-1 gene therapy and PKR modulation might be a promising treatment strategy for
      these tumors that are highly resistant to conventional therapies.

PMID- 16275994
TI  - Determination of the importance of the stereochemistry of psorospermin in
      topoisomerase II-induced alkylation of DNA and in vitro and in vivo biological
      activity.
AB  - Psorospermin is a natural product that has been shown to have activity against
      drug-resistant leukemia lines and AIDS-related lymphoma. It has also been shown
      to alkylate DNA through an epoxide-mediated electrophilic attack, and this
      alkylation is greatly enhanced at specific sites by topoisomerase II. In this
      article, we describe the synthesis of the two diastereomers of O5-methyl
      psorospermin and their in vitro activity against a range of solid and
      hematopoietic tumors. The diastereomeric pair (+/-)-(2'R,3'R) having the
      naturally occurring enantiomer (2'R,3'R) is the most active across all the cell
      lines and shows approximately equal activity in both drug-sensitive and drug
      resistant cell lines. In subsequent studies using all four enantiomers of O5
      methyl psorospermin, the order of biological potency is (2'R,3'R) > (2'R,3'S) =
      (2'S,3'R) > (2'S,3'S). This order of potency is also found in the topoisomerase
      II-induced alkylation of O5-methyl psorospermin and can be rationalized by
      molecular modeling of the psorospermin-duplex binding complex. Therefore, this
      study defines the optimum stereochemical requirements for both the topoisomerase
      II-induced alkylation of DNA and the biological activity by psorospermin and its
      O5-methyl derivatives. Finally, (2'R,3'R) psorospermin was found to be as
      effective as gemcitabine in slowing tumor growth in vivo in a MiaPaCa pancreatic
      cancer model. In addition, (2'R,3'R) psorospermin in combination with gemcitabine
      was found to show an at least additive effect in slowing tumor growth of MiaPaCa.

PMID- 16275993
TI  - Angiogenesis and tumor growth inhibition by a matrix metalloproteinase inhibitor
      targeting radiation-induced invasion.
AB  - In this study, we have evaluated the interactions between ionizing radiation and
      a matrix metalloproteinase (MMP) inhibitor. Using Matrigel invasion assays, we
      show that ionizing radiation induced a dose-dependent increase in the invasive
      phenotype of cultured B16 melanoma cells and that conditioned medium from these
      irradiated B16 cells promoted endothelial cell [human microvascular endothelial
      cells (HMEC)] invasiveness. To determine whether the radiation-induced changes in
      invasive phenotype could be due to changes in MMP activation, we have tested the
      ability of the MMP inhibitor Metastat to modulate the ionizing radiation-induced
      invasive phenotype using both an in vitro melanoma model and a mouse s.c. tumor
      model. In these studies, Metastat inhibited the ionizing radiation-induced
      invasive phenotype in cultured B16 cells and similarly inhibited the increase in
      HMEC invasion induced by conditioned medium from irradiated B16 cells.
      Conversely, ionizing radiation increased B16 MMP-2 activity and the conditioned
      medium from irradiated B16 induced HMEC MMP-2 activity. To further investigate
      the interaction between ionizing radiation and MMP activation, we then studied
      the effects of ionizing radiation on downstream effectors of the MMP system. We
      found that ionizing radiation induced vascular endothelial growth factor (VEGF)
      secretion by B16 melanoma cells and that this secretion was inhibited by
      Metastat. Similarly, conditioned medium from irradiated B16 was also able to
      increase VEGF secretion in HMECs. Moreover, ionizing radiation-induced melanoma
      cell invasiveness was partially inhibited by an anti-VEGF monoclonal antibody. In
      vivo, ionizing radiation plus concomitant Metastat yielded the greatest growth
      inhibition of melanoma s.c. tumors and this effect correlated with inhibition of
      angiogenesis as measured by both Doppler ultrasonography and platelet/endothelial
      cell adhesion molecule-1 staining. Finally, ionizing radiation modulated MMP-2,
      VEGF, and VEGF receptor expression in these tumor samples using
      immunohistochemistry. Taken together, these results suggest that there is an
      ionizing radiation-induced tumor survival pathway and a possible paracrine
      ionizing radiation-induced stimulatory pathway emanating from tumor cells toward
      the endothelial bed that is impeded when Metastat is given simultaneously. This
      model could provide in vivo evidence of the antitumor efficacy of combining a MMP
      inhibitor with ionizing radiation to target radiation-induced invasion and
      angiogenesis.

PMID- 16275995
TI  - The methyltransferase inhibitor 5-aza-2-deoxycytidine induces apoptosis via
      induction of 15-lipoxygenase-1 in colorectal cancer cells.
AB  - DNA methylation by DNA methyltransferases in CpG-rich promoter regions of genes
      is a well-described component of epigenetic silencing in human cells.
      Dysregulation of this process in cancer cells may lead to hypermethylation of
      promoter CpG islands, thus disabling transcription initiation of certain genes,
      such as tumor suppressor genes. Reversing epigenetic silencing and up-regulating
      genes involved in preventing or reversing the malignant phenotype has become a
      new, important targeted approach for cancer prevention and treatment. Therefore,
      methyltransferase inhibitors (MTI) have emerged recently as promising
      chemotherapeutic or preventive agents. The potent MTI 5-aza-2-deoxycytidine (5
      Azadc) causes growth arrest, differentiation, and/or apoptosis of many tumor
      types in vitro and in vivo. The present study shows that low micromolar
      concentrations of 5-Azadc induce the expression of 15-lipoxygenase-1 (15-LOX-1)
      in human colorectal cancer cells. The expression of 15-LOX-1 correlates with 5
      Azadc-induced increases in 13-S-hydroxyoctadecadienoic acid levels, growth
      inhibition, and apoptosis in these cells. Furthermore, specific inhibition of 15
      LOX-1 by pharmacologic means or small interfering RNA significantly reduced the 5
      Azadc-induced effects. These novel findings are the first demonstration of a
      mechanistic link between the induction of 15-LOX-1 by a MTI and apoptosis in
      cancer cells. This result has important implications for the study of 5-Azadc and
      other MTIs in the prevention and therapy of colorectal cancer and supports future
      investigations of the mechanisms by which MTIs up-regulate 15-LOX-1.

PMID- 16275996
TI  - Caspase-dependent apoptosis induction by guggulsterone, a constituent of
      Ayurvedic medicinal plant Commiphora mukul, in PC-3 human prostate cancer cells
      is mediated by Bax and Bak.
AB  - The present study was undertaken to gain insights into the molecular mechanism of
      cell death (apoptosis) by guggulsterone, a constituent of Ayurvedic medicinal
      plant Commiphora mukul, using PC-3 human prostate cancer cells as a model. The
      viability of PC-3 cells, but not a normal prostate epithelial cell line (PrEC),
      was reduced significantly on treatment with guggulsterone in a concentration
      dependent manner. Guggulsterone-mediated suppression of PC-3 cell proliferation
      was not due to perturbation in cell cycle progression but caused by apoptosis
      induction characterized by appearance of subdiploid cells and cytoplasmic histone
      associated DNA fragmentation. Guggulsterone-induced apoptosis was associated with
      induction of multidomain proapoptotic Bcl-2 family members Bax and Bak.
      Interestingly, the expression of antiapoptotic proteins Bcl-2 and Bcl-xL was
      initially increased in guggulsterone-treated PC-3 cells but declined markedly
      following a 16- to 24-hour treatment with guggulsterone. Ectopic expression of
      Bcl-2 in PC-3 cells failed to confer significant protection against guggulsterone
      induced cell death. On the other hand, SV40 immortalized mouse embryonic
      fibroblasts derived from Bax-Bak double knockout mice were significantly more
      resistant to guggulsterone-induced cell killing compared with wild-type cells.
      Guggulsterone treatment resulted in cleavage (activation) of caspase-9, caspase
      8, and caspase-3, and guggulsterone-induced cell death was significantly
      attenuated in the presence of general caspase inhibitor as well as specific
      inhibitors of caspase-9 and caspase-8. In conclusion, the present study indicates
      that caspase-dependent apoptosis by guggulsterone is mediated in part by Bax and
      Bak.

PMID- 16275998
TI  - Inhibition of phosphatidylinositol 3-kinase sensitizes ovarian cancer cells to
      carboplatin and allows adjunct chemotherapy treatment.
AB  - Signal transduction pathways associated with cancer progression and
      chemotherapeutic resistance are being investigated as molecular targets for
      chemotherapy. The phosphatidylinositol 3-kinase (PI3K) pathway has been found to
      be frequently amplified and have increased activity in ovarian cancer. The
      current study investigates the efficacy of an antagonist of PI3K, LY294002, in
      inhibiting ovarian cancer cell growth and survival both in vitro and in vivo. The
      hypothesis tested is that inhibition of PI3K signaling makes ovarian cancer cells
      susceptible to the effects of platinum-based chemotherapy. Observations show that
      LY294002 is an effective inhibitor of ovarian cancer cell growth and survival in
      vitro. Inhibition of PI3K/Akt signaling increased the sensitivity of ovarian cell
      cultures to the cytotoxic effects of carboplatin. The combined treatment of
      LY294002 and carboplatin was needed to optimally promote cellular apoptosis and
      decrease ovarian cancer cell survival in vitro. To extend these observations, a
      model involving in vivo i.p. growth of human ovarian tumors in a nude mouse was
      used. LY294002 in combination with carboplatin was more effective in inhibiting
      ovarian cancer cell xenograft growth than either agent alone. The results of this
      study suggest that the combined treatment of carboplatin and LY294002 can
      effectively decrease ovarian tumor progression and support the use of a PI3K
      inhibitor (e.g., LY294002) as an adjunct platinum-based drug therapy for
      treatment of ovarian cancer.

PMID- 16275997
TI  - Role of O6-alkylguanine-DNA alkyltransferase in the cytotoxic activity of
      cloretazine.
AB  - Cloretazine (VNP40101M; 101M; 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2
      [(methylamino)carbonyl]hydrazine) is a sulfonylhydrazine prodrug that generates
      both chloroethylating and carbamoylating species on activation. To explore the
      molecular mechanisms underlying the broad anticancer activity observed in
      preclinical studies, cloretazine and chloroethylating-only [i.e., 1,2
      bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine] and carbamoylating-only (i.e.,
      1,2-bis(methylsulfonyl)-1-[(methylamino)carbonyl]hydrazine) analogues were
      evaluated in five murine hematopoietic cell lines. These cell lines were
      separable into two groups by virtue of their sensitivity to 1,2
      bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine; the sensitive group included
      L1210, P388, and F-MEL leukemias (IC50s, 6-8 micromol/L) and the resistant group
      consisted of Ba/F3 bone marrow and WEHI-3B leukemia cells (IC50s, 50-70
      micromol/L). Resistant cells expressed O6-alkylguanine-DNA alkyltransferase
      (AGT), whereas sensitive cells did not. A correlation existed between AGT
      expression and the functional status of p53; AGT- cells possessed defective p53,
      whereas AGT+ cells contained wild-type p53. Based on recent findings on
      regulation of AGT gene expression by others, we suspect that silencing of the AGT
      gene by promoter hypermethylation frequently occurs during tumor progression
      involving p53 inactivation. O6-Chloroethylguanine is the initial DNA lesion that
      progresses to lethal interstrand DNA cross-links. Cloretazine exhibited a much
      higher preference toward the O6-chloroethylation of guanine, as measured by the
      difference in IC50s to wild-type and AGT-transfected L1210 cells, than 1,3-bis(2
      chloroethyl)-1-nitrosourea, which targets the same site in DNA. Preferential
      toxicity of cloretazine against AGT- tumor cells coupled with decreased toxicity
      to AGT+ cells in host tissues constitute the therapeutic basis for cloretazine.

PMID- 16275999
TI  - Potentiation of the lethality of the histone deacetylase inhibitor LAQ824 by the
      cyclin-dependent kinase inhibitor roscovitine in human leukemia cells.
AB  - Interactions between the novel histone deacetylase inhibitor LAQ824 and the
      cyclin-dependent kinase inhibitor roscovitine were examined in human leukemia
      cells. Pretreatment (24 hours) with a subtoxic concentration of LAQ824 (30
      nmol/L) followed by a minimally toxic concentration of roscovitine (10
      micromol/L; 24 hours) resulted in greater than additive effects on apoptosis in
      U937, Jurkat, and HL-60 human leukemia cells and blasts from three patients with
      acute myelogenous leukemia. These events were associated with enhanced
      conformational changes in Bax; mitochondrial release of cytochrome c,
      Smac/DIABLO, and apoptosis-inducing factor; and a marked increase in caspase
      activation. LAQ824/roscovitine-treated cells displayed caspase-dependent down
      regulation of p21(CIP1) and Mcl-1 and a pronounced caspase-independent reduction
      in X-linked inhibitor of apoptosis (XIAP) expression. The lethality of this
      regimen was significantly attenuated by ectopic expression of XIAP, a nuclear
      localization signal-defective p21(CIP1) mutant, Mcl-1, and Bcl-2. Combined
      exposure to LAQ824 and roscovitine resulted in a significant reduction in XIAP
      mRNA levels and diminished phosphorylation of the carboxyl-terminal domain of RNA
      polymerase II. Notably, roscovitine blocked LAQ824-mediated differentiation.
      Finally, LAQ824 and roscovitine individually and in combination triggered an
      increase in generation of reactive oxygen species; moreover, coadministration of
      the free radical scavenger N-acetylcysteine prevented LAQ824/roscovitine-mediated
      mitochondrial injury and apoptosis. Collectively, these findings suggest that
      combined treatment of human leukemia cells with LAQ824 and roscovitine disrupts
      maturation and synergistically induces apoptosis, lending further support for an
      antileukemic strategy combining novel histone deacetylase and cyclin-dependent
      kinase inhibitors.

PMID- 16276000
TI  - Subsieve-size agarose capsules enclosing ifosfamide-activating cells: a strategy
      toward chemotherapeutic targeting to tumors.
AB  - Localized activation of the prodrug ifosfamide in or close to tumors by
      implanting encapsulated ifosfamide-activating cells is an efficacious strategy
      for tumor therapy. The aim of this study was to evaluate the feasibility of
      subsieve-size agarose capsules for enclosing the cells in this application.
      Compared with many conventional microcapsules, subsieve-size agarose capsules are
      about one-tenth the size and have both higher mechanical stability and allow
      better molecular exchangeability than other systems. Cells that have been
      genetically modified to express cytochrome P450 2B1 enzyme were encapsulated in
      subsieve-size agarose capsules of approximately 90 microm in diameter and
      implanted into preformed tumors in nude mice. Living cells were detected for >1
      month after encapsulation in vitro and showed enzymatic activity (i.e., they were
      able to activate ifosfamide). More significant regression of preformed tumors was
      observed in the recipients implanted with cell-enclosing capsules compared with
      those implanted with empty capsules. These results suggest that the strategy of
      using subsieve-size agarose capsules enclosing cytochrome P450 2B1-expressing
      cells is feasible for tumor therapy by chemotherapeutic targeting in combination
      with ifosfamide administration.

PMID- 16276001
TI  - A beta-lactamase with reduced immunogenicity for the targeted delivery of
      chemotherapeutics using antibody-directed enzyme prodrug therapy.
AB  - Antibody-directed enzyme prodrug therapy (ADEPT) delivers chemotherapeutic agents
      in high concentration to tumor tissue while minimizing systemic drug exposure.
      beta-Lactamases are particularly useful enzymes for ADEPT systems due to their
      unique substrate specificity that allows the activation of a variety of lactam
      based prodrugs with minimal interference from mammalian enzymes. We evaluated the
      amino acid sequence of beta-lactamase from Enterobacter cloacae for the presence
      of human T-cell epitopes using a cell-based proliferation assay using samples
      from 65 community donors. We observed a low background response that is
      consistent with a lack of preexposure to this enzyme. beta-Lactamase was found to
      contain four CD4+ T-cell epitopes. For two of these epitopes, we identified
      single amino acid changes that result in significantly reduced proliferative
      responses while retaining stability and activity of the enzyme. The beta
      lactamase variant containing both changes induces significantly less
      proliferation in human and mouse cell assays, and 5-fold lower levels of IgG1 in
      mice were observed after repeat administration of beta-lactamase variant with
      adjuvant. The beta-lactamase variant should be very suitable for the construction
      of ADEPT fusion proteins, as it combines high activity toward lactam prodrugs,
      high plasma stability, a monomeric architecture, and a relatively low risk of
      eliciting an immune response in patients.

PMID- 16276002
TI  - Human single-domain neutralizing intrabodies directed against Etk kinase: a novel
      approach to impair cellular transformation.
AB  - Etk, the 70-kDa member of the Tec family of nonreceptor protein tyrosine kinases,
      is expressed in a variety of hematopoietic, epithelial, and endothelial cells and
      was shown to be involved in several cellular processes, including proliferation,
      differentiation, and motility. In this study, we describe a novel approach using
      a human single-domain antibody phage display library for the generation of
      intrabodies directed against Etk. These single-domain antibodies bind
      specifically to recombinant Etk and efficiently block its kinase activity. When
      expressed in transformed cells, these antibodies associated tightly with Etk,
      leading to significant blockade of Etk enzymatic activity and inhibition of
      clonogenic cell growth in soft agar. Our results indicate that Etk may play a
      role in Src-induced cellular transformation and thus may represent a good target
      for cancer intervention. Furthermore, our single-domain antibody-based intrabody
      system proves to be an excellent tool for future intracellular targeting of other
      signaling molecules.

PMID- 16276003
TI  - Clinical translation of epigenetics in cancer: eN-CORe--a report on the second
      workshop.
AB  - Recent advances in understanding the role that epigenetics plays in cancer
      pathogenesis and understanding the mechanisms through which these processes
      regulate gene expression have stimulated considerable interest in developing
      clinically viable antineoplastic agents that target enzymatic components of
      transcriptional regulatory complexes responsible for the establishment of
      pathologic epigenetic modifications that lead to deregulated gene expression in
      cancer. In January 2003, a workshop was held in Baltimore to discuss the
      therapeutic potential of several agents that can modify chromatin structure. A
      follow-up meeting on "Clinical Translation of Epigenetics in Cancer" was held in
      Charleston, SC, in January 2005. The aim of this workshop was to assess the
      progress that has been made over the past 2 years in bringing effective
      therapeutic protocols that use agents capable of reverting pathologic epigenetic
      changes into the clinic. The meeting was attended by approximately 70
      investigators and included formal presentations, panel group discussions, and two
      break-out sessions that addressed targeted therapies in hematologic and solid
      tumors. The aim of this article is to summarize topics discussed at this workshop
      and highlight conclusions as to the immediate and long-term future of epigenetic
      therapy in cancer.

PMID- 16276004
TI  - Circulating nucleic acids in plasma or serum (CNAPS) as prognostic and predictive
      markers in patients with solid neoplasias.
AB  - It is now widely accepted that there is a need for the development of molecular
      markers of cancer that can be used for clinical prognostication and monitoring.
      Approximately a decade ago tumor-derived circulating nucleic acids in the plasma
      or serum (CNAPS) of cancer patients were introduced as a noninvasive tool for
      cancer detection. This review focuses on the various types of CNAPS of patients
      with solid neoplasias (genetic alterations in circulating DNA, microsatellites,
      methylated DNA, viral DNA, nucleosomes, mitochondrial DNA and cell-free mRNA) and
      their putative potential as prognostic or predictive parameter or even as a tool
      for therapy monitoring during follow-up. Additionally, this review aims to point
      out the difference between a prognostic and a predictive factor in patient
      bloodstream. However, with rapid technical improvement and well-designed studies
      we conclude that the next years will see CNAPS analysis integrated in the
      prognostication and monitoring of cancer patients, thus producing more specific
      treatment regimens for patients with various stages of neoplastic disease and
      ultimately longer survival and better quality of life.

PMID- 16276005
TI  - MUC gene abnormalities in sporadic and hereditary mucinous colon cancers with
      microsatellite instability.
AB  - Aim of this study was verifying whether mucin producing colon cancers (CRCs)
      could develop through a molecular pathway involving microsatellite instability
      (MSI) and MUC gene alterations. Out of 49 CRCs expressing variable amounts of
      mucin, 22 (44.9%) were MSI-H and 5 (10.2%) were MSI-L. MUC genes were analyzed by
      Southern blotting and extra bands were evident in the Variable Number Tandem
      Repetition (VNTR) regions of MUC2 (5 cases) and MUC5AC (2 cases), but not MUC1
      and MUC4 genes. Since the somatic VNTR abnormalities were detected in 6 MSI-H and
      in 1 MSI-L tumors, they seem to be peculiar of mismatch repair defective CRCs.
      Our finding suggests that alteration and/or loss of structurally normal MUC genes
      may be an important step in the neoplastic molecular pathway of a subset of CRCs
      and that mutations involving VNTR repetitive sequences may exist in MSI tumors as
      a direct and/or indirect consequence of an inefficient MMR system.

PMID- 16276006
TI  - The application of plasma 1,5-anhydro-D-glucitol for monitoring type 2 diabetic
      patients.
AB  - AIM: Recent data have suggested that effective control of postprandial blood
      glucose can reduce the risk of macroangiopathic complications of diabetes,
      especially cardiovascular risk. 1,5-Anhydro-D-glucitol (1,5-AG) has been proposed
      as a marker of short-term hyperglycaemic excursions. We aimed to evaluate its
      usefulness in patients with type 2 diabetes and have attempted to indicate when
      1,5-AG monitoring should be used in ordinary diabetes care settings. METHODS: The
      study group consisted of 130 type 2 diabetic patients aged 36-69 years. 1,5-AG
      plasma level, HbA_1c concentrations and daily glucose profile were measured. Mean
      blood glucose (MBG), M-value were calculated and maximal daily glycaemia (MxG)
      was established as indicators of short-term hyperglycaemic episodes. RESULTS: 1,5
      AG plasma level was negatively and HbA_1c was positively correlated with fasting
      glycaemia (FG), MBG, M-value and MxG. Multivariate regression analysis revealed
      that 1,5-AG plasma level is determined by MxG only, while FG determined HbA_1c
      concentration in blood. The analysis of 1,5-AG level and HbA_1c distributions in
      well and poorly controlled patients revealed that persons with low HbA_1c values
      may have decreased 1,5-AG plasma level. CONCLUSION: 1,5-AG plasma level
      monitoring is the useful method to identify well controlled, exclusively based on
      HbA_1c levels type 2 diabetic patients with transient hyperglycaemia, accordingly
      patients at high risk of macroangiopathic complications.

PMID- 16276007
TI  - Salivary thiobarbituric acid reacting substances and malondialdehyde--their
      relationship to reported smoking and to parodontal status described by the
      papillary bleeding index.
AB  - BACKGROUND: Thiobarbituric reacting substances (TBARS) are markers of
      lipoperoxidation. The best-known specific TBARS is malondialdehyde (MDA). Results
      from our previous studies have shown that TBARS can be measured in saliva and are
      increased in patients with gingivitis. Whether MDA is the main TBARS in saliva
      from patients with altered parodontal status is unknown. Aim. To observe the
      relationship between the parodontal status and TBARS, MDA and the number of
      epithelial cells in saliva. SUBJECTS & METHODS: In Study I saliva and plasma
      samples of 15 patients (8F, 7M) suffering from inflammatory periodontal diseases
      were gathered and TBARS levels were measured in these samples. In Study II saliva
      samples from 217 consecutive stomatologic patients were collected and analysed
      for TBARS spectrofluorometrically, MDA by high-performance liquid chromatography
      and epithelial cell count by light microscopy. Papillary bleeding index (PBI) was
      determined in standard stomatologic examination. RESULTS: In Study I results from
      our previous studies showing no correlation between salivary and plasma TBARS
      levels were confirmed. This indicates that the local salivary level of TBARS is
      unlikely to be directly affected by systemic oxidative stress. In Study II higher
      PBI was associated independently (adjusted for age and sex) tightly with higher
      TBARS (p<0.001) and with lower number of epithelial cells in saliva (p<0.05).
      Smokers had higher salivary MDA levels (p<0.003) and lower number of epithelial
      cells in saliva (p<0.01). CONCLUSION: Salivary TBARS are a simple parameter that
      partially reflects the parodontal status with a potential usefulness in the
      clinical stomatology. We show herein that salivary MDA is dependent on age and
      smoking, but there is no correlation between MDA and PBI. Further studies should
      uncover the main salivary TBARS compound in patients with altered parodontal
      status and trace the origin of these salivary lipoperoxidation markers.

PMID- 16276008
TI  - Estimation of diabetes risk in Brazilian population by typing for polymorphisms
      in HLA-DR-DQ, INS and CTLA-4 genes.
AB  - The study aimed to further characterise HLA encoded risk factors of type 1
      diabetes (T1D) in Brazilian population and test the capability of a low
      resolution full-house DR-DQ typing method to find subjects at diabetes risk.
      Insulin and CTLA-4 gene polymorphisms were also analysed. The method is based on
      an initial DQB1 typing supplemented by DQA1 and DR4 subtyping when informative.
      Increased frequencies of both (DR3)-DQA1*05-DQB1*02 and DRB1*04-DQA1*03-DQB1*0302
      haplotypes were detected among patients. DRB1*0401, *0402, *0404 and *0405
      alleles were all common in DQB1*0302 haplotypes and associated with T1D.
      (DRB1*11/12/1303)-DQA1*05-DQB1*0301, (DRB1*01/10)-DQB1*0501, (DRB1*15)-DQB1*0602
      and (DRB1*1301)-*0603 haplotypes were significantly decreased among patients.
      Genotypes with two risk haplotypes or a combination of a susceptibility
      associated and a neutral haplotype were found in 78 of 126 (61.9%) T1D patients
      compared to 8 of 75 (10.7%) control subjects (P < 0.0001). Insulin gene -2221 C/T
      polymorphism was also associated with diabetes risk: CC genotype was found among
      83.1% of patients compared to 69.3% of healthy controls (P=0.0369, OR 1.98) but
      CTLA-4 gene +49 A/G polymorphism did not significantly differ between patients
      and controls. Despite the diversity of the Brazilian population the screening
      sensitivity and specificity of the used method for T1D risk was similar to that
      obtained in Europe.

PMID- 16276009
TI  - Patterns of global DNA and histone methylation appear to be similar in normal,
      dysplastic and neoplastic oral epithelium of humans.
AB  - Although there is growing interest in the possibility that alterations in histone
      methylation may play a role in carcinogenesis, it has not been explored
      adequately in humans. Similarly, there are no reports of associations between
      this and a similar epigenetic event, DNA methylation. Using immunohistochemical
      staining, we compared the methylation of DNA and histones in histopathologically
      normal oral epithelium, dysplastic oral lesions, and squamous cell cancers (SCCs)
      from subjects with squamous cell cancer (n=48) with those of normal oral
      epithelium from subjects without oral cancer (n=93) who were matched on age and
      race. Monoclonal antibodies specific for 5 methyl cytosine (5-mc), lysine 4 of
      histone H_3 (H_3-Lys4), and lysine 9 of histone H_3 (H_3-Lys9) were used in this
      study. The percentages of cells positive and a weighted average of the
      immunostaining intensity scores were calculated for each of these tissues, and
      Spearman correlation analyses were employed to study associations between DNA and
      histone methylation. Correlations between DNA and histone methylation, H_3-Lys4
      and H_3-Lys9 were positive and statistically significant in all tissue types;
      they were strongest in normal oral epithelium from non-cancer subjects (r=0.63, p
      < 0.001 and r=0.62, p < 0.001 respectively). Similarly, the positive correlations
      between H_3-Lys4 and H_3-Lys9 were statistically significant in all tissue types
      and strongest in normal oral epithelium from non-cancer subjects (r=0.77, p<
      0.001). Patterns of DNA and histone methylation are similar in tissues across the
      spectrum of oral carcinogenesis, and there is a significant positive association
      between these two epigenetic mechanisms.

PMID- 16276010
TI  - epsilon3epsilon4 genotype as risk factor of myocardial infarction in middle-aged
      people in Spain.
AB  - Apolipoprotein E (apoE) plays an important role in lipid metabolism. Its epsilon4
      allele has been consistently associated with lipoprotein disorders but its
      connection to myocardial infarction (MI) is controversial. Because epsilon4
      frequency decreases with age we thought that the contradictory results in
      different studies could be due to the wide age range of the subjects included. To
      test our hypothesis, ApoE genotyping was performed in 474 MI cases and an
      analysis was performed by percentiles of age. The frequencies of epsilon3epsilon4
      genotype and epsilon4 allele in the MI group as a whole (subjects aged 31 to 92)
      were not significantly different from those in our area general population.
      However, significant differences were observed when comparing by group of age.
      The frequencies decreased as age increased. The epsilon3epsilon4 and epsilon4
      frequencies were significantly higher in MI subjects aged 31 to 56 than in
      subjects over 74. The epsilon3epsilon4 genotype prevalence in an age and sex
      matched control group of subjects aged 31 to 56 was significantly lower than in
      the 31-56 year-old MI group. In conclusion, our data shows different
      epsilon3epsilon4 and epsilon4 frequencies depending on the age range of the
      subjects with MI, being significantly higher in the middle-aged group. This
      finding may help explain the discrepancies between studies analyzing association
      between apoE genotype and MI, and emphasizes the idea of considering apoE
      genotype for prevention at early age.

PMID- 16276011
TI  - TNF-alpha, TNF-beta, IL-6, and IL-10 polymorphisms in patients with lung cancer.
AB  - Apart from cigarette smoking, genetic factors seem to be of importance in the
      development of lung cancer. The present case-control study investigated
      frequencies of five inflammatory response gene polymorphisms (TNF-alpha-308, TNF
      beta-Intron1-252, IL-6-174, IL-10-819 and IL-10-1082) in patients with lung
      cancer and controls. The study population consisted of 117 patients with lung
      cancer (77 patients with NSCLC, including 40 Squamous Cell Carcinoma and 26
      Adenocarcinoma, and 40 patients with SCLC), 117 matched controls without
      pulmonary disease and 243 healthy individuals (population control). Genotype
      analyses revealed no difference in genotype frequencies using matched-pair
      analysis. However, in comparison to the population control, the IL-10-1082
      genotypes carrying the G allele appeared with higher frequency in the SCLC group
      (p=0.006) [SCLC: 84.6%, population controls: 64.6%]. This yields an odds ratio of
      3.01 for SCLC (95% CI = [1.21, 7.48]). No associations were seen for all other
      polymorphisms analysed. The study raises the possibility of a correlation between
      the IL-10-1082_G allele and the presence of SCLC in a German population. The
      functional IL-10-1082 polymorphism correlates with altered IL-10 levels and might
      influence lung cancer susceptibility by altered inflammatory responses in the
      airways.

PMID- 16276012
TI  - Quality of life measures in lung cancer.
AB  - Lung cancer is one of the leading causes of cancer death worldwide. Survival has
      not improved significantly in spite of newer therapies. In view of the high
      symptom burden and severe morbidity, evaluation of quality of life (QOL) becomes
      important in these patients. Several instruments are now available for this
      purpose, and have demonstrated good correlation with performance status,
      symptoms, and survival. Quality of life assessments also help in comparing
      different therapeutic regimes, thus allowing selection of the appropriate
      modality. Problems of inconsistent interpretability and high-patient dropout rate
      poses a challenging problem that needs to be tackled. In spite of these
      drawbacks, QOL is now considered to be an essential component of lung cancer
      management and should be performed routinely. Such a practice will help the
      physician plan appropriate treatment strategies and set practical therapeutic
      goals.

PMID- 16276013
TI  - Role of external irradiation in high-risk resected colon cancer.
AB  - BACKGROUND/AIM: The best therapeutic modality for colon cancer "one of the most
      common malignancies of human being" is surgical resection of primary tumor.
      Adjuvant chemotherapy can help surgery to have a higher control and survival rate
      in high-risk resected patients, but the role of radiation therapy is the place of
      debate. This study was carried out to evaluate the possible role of adjuvant
      radiotherapy in such cases. MATERIALS AND METHODS: This retrospective trial
      evaluated 65 eligible patients with surgically resected high-risk colon carcinoma
      (serosal and/or lymph node involvement), from May 1986 to February 2000. The
      patients were categorized into two groups. The first group was treated with
      chemotherapy alone and the other with chemo-radiotherapy. Chemotherapy included
      5.FU 500 mg/m2sub/5days for 6-8 courses and radiotherapy consisted 45-55 Gy with
      1.5-2 Gy/fraction. Minimum follow-up was 36 months. RESULTS: Mean event-free
      survival was 140 and 101 months in chemotherapy and combined-therapy groups,
      respectively (P = 0.099). Local recurrence rate was detected as 9.7% in the
      chemotherapy arm and 23.5% in the combined-therapy arm (P > 0.1). Treatment
      related morbidity and mortality has been significantly higher in the radiation
      arm (P < 0.001). CONCLUSION: Postoperative external radiation as adjuvant
      treatment does not improve local control of the patients with colon carcinoma.

PMID- 16276014
TI  - Validation of quality of life questionnaire for patients with cancer--Indian
      scenario.
AB  - BACKGROUND: Quality of Life (QOL) is an important health outcome measure in
      oncology. Given the underlying pressure of individual geo-political entities, a
      universal solution may not be applicable and hence there is a need to develop a
      regional tool and standardize the same to address the linguistic and socio
      cultural factors. OBJECTIVE: To standardize a tool to assess the QOL of patients
      with cancer to suit the Indian scenario. MATERIALS AND METHODS: The samples were
      collected from the Cancer Institute (WIA), Chennai. Samples comprise of 400
      patients with all sites and stages of cancer. PERIOD: January 2001 to January
      2002. Patients were in the age range of 41-60 years. Thirty-eight items were
      pooled from existing tools, reviews, and the field trial, by which face and
      factorial validity were established. Reliability of the tool was also tested.
      Correlation analysis was done to find out the relation between the domains of
      QOL. STATISTICS USED: Principal component method with varimax rotation was used.
      Spearmen product moment correlation and Cronbach alpha coefficient were used for
      reliability analysis. RESULTS: Ten factors emerged with Eigen values ranging from
      8.55 to 1.10 and accounted for 62.6% of variance. The first factor contributed
      maximally, 22% of variance. The remaining nine factors contributed totally to 40%
      of the variance on QOL. The ten factors that emerged were psychological well
      being, self-adequacy, physical well being, confidence in self-ability, external
      support, pain, mobility, optimism and belief, interpersonal relationship and self
      sufficiency and independence. The internal consistency using Cronbach alpha test
      was 0.90 and split-half reliability was 0.74. CONCLUSION: The tool was found to
      be highly reliable and valid. It was feasible to administer it at clinical
      settings.

PMID- 16276015
TI  - Surgical management of skin cancers: experience from a regional cancer centre in
      North India.
AB  - AIMS: To review the disease profile and treatment outcome of patients with
      primary skin malignancies treated at a regional cancer centre. SETTINGS AND
      DESIGN: Surgical oncology unit of a tertiary care regional cancer centre.
      Evaluation of treatment outcome of patients with skin cancer from Surgical
      Oncology database was done. MATERIALS AND METHODS: Retrospective analysis of
      records of 77 patients with skin cancers treated between 1995 and 2002 was
      conducted. Profile of patients with skin cancer, surgical details including the
      management of primary tumour, regional lymph nodes and reconstructive procedures
      performed and survivals were analysed. STATISTICAL ANALYSIS: All computations
      were done using the Statistical Package for Social Sciences (SPSS-9). Descriptive
      statistics were calculated in a standard fashion and survival analysis was
      performed using Kaplan-Meier method. RESULTS: Skin cancers constituted 2.4%
      (77/3154) of patients with cancer treated in the surgical oncology department.
      Squamous cell carcinoma (SCC) was the most common histological type (55.8%)
      followed by melanoma (26.1%) and basal cell carcinoma (BCC, 18.1%). Forty one
      percent of patients had undergone some form of intervention elsewhere before
      being referred. Reconstruction was required in 55.8% patients with large
      postresection defects. Regional lymph nodal dissection was required in 32.4% of
      total patients. Five-year median disease-free survival for the entire study
      population was 75%. CONCLUSIONS: Skin cancers constitute a small but significant
      proportion of patients with cancer. Unlike in the Western countries, SCC is the
      commonest histologic variety. Primary level inadequate intervention is very
      common. Optimal results can be obtained with radical surgery and optimal surgical
      margins along with a reconstructive procedure when needed.

PMID- 16276016
TI  - Transrectal ultrasound guided biopsy for detecting early prostate cancer: An
      Indian experience.
AB  - BACKGROUND: With the advent of prostate specific antigen the number of patients
      undergoing prostate biopsy has dramatically increased. The sextant biopsy
      technique has been conventionally used for the diagnosis of prostate cancer.
      Recently, concern has arisen that the original sextant method may not include an
      adequate sample of the prostate, hence it may result in high false negative
      rates. We conducted a prospective study to determine whether the 5-region
      prostate biopsy technique significantly increases the chance of prostate cancer
      detection as compared to the sextant biopsy technique. AIMS: To evaluate the
      efficacy of TRUS guided sextant and 5-region biopsy techniques in detecting
      carcinoma prostate in patients with PSA between 4 and 10 ng/ml and normal digital
      rectal examination. METHODS AND MATERIAL: Between December 2001 and August 2003
      one forty-two men, aged 49-82 years, who presented with LUTS, normal digital
      rectal examination (DRE) and PSA between 4 and 10 ng/ml underwent TRUS guided
      sextant prostate biopsy. Serum PSA was reassessed after 3 months in patients
      whose biopsies were negative for cancer. If PSA was still raised, the patients
      underwent extensive 5-region biopsy. RESULTS: Mean patient age was 64 years and
      median PSA was 6.9 ng/ml. TRUS guided sextant biopsy revealed adenocarcinoma
      prostate in 34 men (24%). Median Gleason score was 7. Seven men (4.9%) had
      cellular atypia and 3(2.1%) had prostatic intraepithelial neoplasia (high grade).
      On repeat PSA estimation after 3 months, 48 patients showed stagnant or rising
      trend for which they underwent TRUS guided 13-core biopsy. Five (10.4%) patients
      were detected to have adenocarcinoma on repeat biopsy. Biopsy negative patients
      are on regular follow up with yearly PSA estimation. Complications included
      transient mild haematuria in14 patients (9.82%) and haematospermia in 4 (2.8%).
      Urinary retention developed in one patient and required an indwelling catheter
      for 4 days. CONCLUSION: Transrectal ultrasound guided sextant biopsy has shown a
      false negative rate of approximately 11%. A repeat 5- region (13-core) biopsy
      strategy can decrease the false negative rate of conventional sextant biopsy in
      patients with previously negative biopsies but persistently high PSA levels, high
      grade PIN or cellular atypia.

PMID- 16276017
TI  - Catheter fracture and cardiac migration of a totally implantable venous device.
AB  - Totally implantable venous devices (TIVD) are increasingly being utilized for
      venous access for chemotherapy of oncological patients. These devices
      considerably improve the quality of life of patients requiring long-term
      chemotherapy. However, despite the great usefulness of TIVDs, their insertion and
      maintenance is not free of complications. Many early as well as late
      complications associated with these devices have been reported. We report an
      unusual, silent, but potentially hazardous complication of catheter fracture and
      cardiac migration in a 16-year-old girl, in whom the port had been unused for 9
      months before presentation. Percutaneous retrieval was unsuccessful as the
      catheter end was embedded in the myocardium. The catheter was removed via a
      midline sternotomy without any further complications. We have also reviewed the
      literature about the possible mechanism of this complication and discussed
      methods to recognize and avoid it.

PMID- 16276018
TI  - Hodgkin's disease in an elderly patient with B-cell chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common type of leukemia worldwide.
      It is an indolent disease, almost exclusively of B-cell origin. Some CLLs evolve
      into a more aggressive lymphoid malignancy. The most common of these is Richter's
      syndrome. Transformation to acute lymphoblastic leukemia, plasma cell leukemia,
      multiple myeloma, or Hodgkin's disease (HD) may also occur. CLL patients are also
      at a significantly increased risk of developing a second malignant neoplasm later
      in life. One of the most common of these is HD. Herein, we report a case of HD in
      an elderly man with a history of B-cell CLL.

PMID- 16276019
TI  - Rare thoracic mass lesion--myofibrobastoma.
AB  - Mesenchymal soft tissue masses are uncommon tumours of the chest.
      Myofibroblastoma is a recently described entity consisting of cells with origin
      from the myoepethelial cell, mostly seen as benign well-circumscribed neoplasms
      of the breast tissue. Though usually classified as a benign lesion, rarely it can
      be multifocal and prone to recurrence. We describe below the case of a 26-year
      old female who presented with exertional dyspnoea and evidence of a massive mass
      lesion in the left hemithorax causing mediastinal displacement to the opposite
      side. On histological and immunophenotypic analysis, a diagnosis of the very rare
      thoracic myofibroblastoma was made. The incidence, salient features, pathological
      differential diagnoses and treatment are reviewed.

PMID- 16276020
TI  - Mature ovarian teratoma with gliomatosis peritonei--a case report.
AB  - Gliomatosis peritonei (GP), a rare condition related to ovarian teratomas, is
      characterized by miliary implants of mature glial tissues on the peritoneum or
      omentum. We report herein a case of mature teratoma of the ovary with GP with
      imaging features and pathological correlation.

PMID- 16276021
TI  - The cryofixation of isolated rat gastric mucosa provides new insights into the
      functional transformation of gastric parietal cells: an in vitro experimental
      model study.
AB  - Cryofixation is currently accepted as the best initial fixation step to preserve
      not only the fine structure but also the antigenicity of biological samples. To
      elucidate the functional transformation of gastric parietal cells, we have newly
      developed an in vitro experimental model, named the isolated gastric mucosa. In
      this study, acid secretion of the parietal cell was stimulated with histamine or
      inhibited with cimetidine, and the samples were cryofixed by plunge freezing for
      light microscopy or high-pressure freezing for electron microscopy. As a result,
      the organization of glandular cells was well-preserved and quite similar to
      freshly excised rat gastric mucosa for at least 2 h after isolation.
      Immunohistochemistry of H+/K+-ATPase demonstrated a translocation of H+/K+-ATPase
      from the cytoplasm to the apical membrane associated with histamine-stimulation.
      In cimetidine-treated mucosa, most of the parietal cells were morphologically in
      the resting state, showing numerous tubulovesicles in their cytoplasm. In
      contrast, histamine-stimulated parietal cells exhibited well-developed
      intracellular canaliculi lined with long microvilli. To the best of our
      knowledge, the present study is first to demonstrate an electron micrograph that
      strongly suggests a membrane fusion between the tubulovescile and the apical
      membrane. Moreover, a stimulation-associated translocation of ezrin was clearly
      shown from the cytoplasm to the apical region, corresponding to apical microvilli
      development in the isolated gastric mucosa model. We here describe the
      preparation of the isolated rat gastric mucosa model, which provides new insights
      into the functional transformation of parietal cells by the application of
      cryotechniques.

PMID- 16276022
TI  - Functional ability of tendinocytes to take up Fe substances in an inflamed
      tendon.
AB  - The fate of iron (Fe) after bleeding has been analyzed in various connective
      tissues, but there have been only a few inconclusive studies on Fe in the tendon.
      In this study, energy dispersive X-ray microanalysis and an iron staining method
      were used to determine the localization of Fe in cells of the equine superficial
      digital flexor tendon. In inflamed tendons, Fe was detected in tendinocytes as
      well as macrophages. In contrast, negative or weak reactions were observed in
      many cells in the normal tendon. Although the accepted theory states that the
      reticuloendothelial system (macrophages and reticuloendothelial cells) is mainly
      responsible for the uptake and decomposition of erythrocytes, and tendon cells
      under conditions of inflammation show a functional ability to take up Fe
      substances. It has been reported that tendinocytes have multiple functions,
      including synthesis and secretion of collagen, cytokines, and matrix
      metalloproteinases. Taking these functions into consideration, indicates that the
      tendinocyte is not only an active cell but also a multi-functional cell.

PMID- 16276023
TI  - The presence of ferric and ferrous iron in the nonheme iron store of resident
      macrophages in different tissues and organs: histochemical demonstrations by the
      perfusion-Perls and -Turnbull methods in the rat.
AB  - We previously developed the highly sensitive perfusion-Perls and -Turnbull
      methods to visualize nonheme ferric (Fe (III)) and ferrous (Fe (II)) iron,
      respectively. The present study used these methods to investigate the possible
      presence of nonheme iron in the redox (ferric/ferrous) state in the noneheme iron
      store (phagolysosomes and siderosomes) of resident macrophages in the rat. The
      perfusion-Perls and -Turnbull methods at pH 0.6 supplemented by DAB
      intensification intensely stained resident macrophages of different tissues and
      organs of normal and iron-overloaded rats. The perfusion-Turnbull method, which
      is specific for nonheme Fe (II), partly stained hemosiderin at pH 5.3, but hardly
      stained it at the physiological pH, suggesting the presence of some iron in the
      reduced form, free Fe2+ and/or loosely bound Fe (II), at the intravacuolar pH
      (5.4+/-0.2) of the phagolysosomes of macrophages. Electron microscopy of the
      splenic and hepatic macrophages treated by the perfusion-Perls or -Turnbull
      method showed that Fe (II) deposits were largely distributed along the margin of
      hemosiderin masses while Fe (III) deposits could also be found within hemosiderin
      masses.

PMID- 16276024
TI  - Morphological changes in oral mucosae and their connective tissue cores regarding
      oral submucous fibrosis.
AB  - Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity
      characterized by an inflammatory reaction followed by severe fibro-elastic
      changes. The aim of the present study was to investigate the three-dimensional
      morphological changes in the connective tissue cores (CTCs) of the oral mucosa in
      OSF. The sample consisted of buccal mucosal biopsies from ten human subjects
      ranging in age from 40-45 years; five of them were clinically diagnosed as having
      moderate to severe OSF, and the remaining five served as unaffected controls.
      Half of each biopsy was formalin-fixed and paraffin-embedded for light
      microscopy, while the other half was fixed in a Karnovsky's solution, treated
      with HCl to exfoliate the epithelium, and processed for examination under a
      scanning electron microscope (SEM). Oral submucous fibrosis biopsies exhibited
      heavily packed aldehyde fuchsin-positive fibers (i.e. elastic fibers) in the
      submucosa under the light microscope. Broad bundles of collagen fibers were seen
      in a concentrated manner in the deeper layers. Scanning electron microscopy of
      the buccal mucosa in OSF showed the finger-shaped CTCs to be attenuated beneath
      the epithelium at the initial stages of the disease. Patchy degenerative areas
      lacking the CTCs were observed in advanced cases. These degenerative areas
      increased gradually with the progression of the disease. Highly fibrosed cases
      showed severe degeneration of the CTCs, resulting in a smoothening of the
      connective tissue surface in the buccal mucosa.

PMID- 16276025
TI  - Glycoconjugate histochemistry of the secretory epithelium lining the seminal
      vesicles of the miniature pig.
AB  - The present study thoroughly examined the localization and characterization of
      glycoconjugates in the secretory epithelium lining the seminal vesicles of the
      miniature pig, employing light and electron microscopic histochemical procedures,
      including lectin methods. The present results showed the epithelial cells and
      luminal secretions to contain glycoconjugates with abundant neutral saccharides
      and a small amount of acidic saccharides, containing varying types of terminal
      sugar residues. At ultrastructural levels, the free surface coat of the plasma
      membrane was rich in alpha-D-Man, alpha-D-Glc, beta-D-Gal, GlcNAc, and sialic
      acid. The flocculent contents of the secretory vesicles indicated the
      localization of alpha-D-Man, alpha-D-Glc, alpha-L-Fuc, beta-D-Gal, GlcNAc, and
      sialic acid; such sugar residues were also seen in the elements of the Golgi
      apparatus. The present results have characterized the seminal vesicles of the
      miniature pig as having a high secretory activity and copiously producing
      glycoconjugates with various sugar residues. Such glycoconjugates appear to be
      indispensable substances for porcine reproduction, possibly influencing the
      fertilizing capacity of spermatozoa within the female genital tract.

PMID- 16276026
TI  - Ultrastructural alterations of the cortical epithelial cells of the irradiated
      and recovering rat thymus.
AB  - To understand the roles of cortical thymic epithelial cells (CTECs) in T
      lymphocyte development, we analyzed rat thymi recovering from irradiation (6Gy),
      at the ultrastructural level. The morphological alterations in the CTECs were
      most prominent during the third to fifth day of recovery, when proliferating
      thymocytes were observed in the vicinity of the CTECs. The most striking finding
      among the alterations in the CTECs after irradiation was a cytoplasmic
      vacuolization with an increased amount of granular and membranous content. The
      granular content was observed as loosely aggregated structures or finely
      dispersed granules and dense bodies. The membranous content appeared in various
      forms including vesicular, tubular, and irregular membranous structures and
      myelin figures. The above features are characteristic of the hyperfunctional
      state of CTECs with increased secretion activities, which suggests their
      important roles in the repopulation and maturation of the cortical thymocytes
      during recovery after irradiation.

PMID- 16276027
TI  - Segment-specific expression of tight junction proteins, claudin-2 and -10, in the
      rat epididymal epithelium.
AB  - Tight junctions are known to be related to the variance by segment of the luminal
      fluid microenvironment of the epididymis. We examined the expression of claudins
      that regulate the paracellular permeability of ions, solutes, and water through
      tight junctions in the rat epididymis. RT-PCR analysis showed that claudin-2 and 
      10 were expressed in a segment-specific manner among fifteen claudins examined.
      Immunofluorescence microscopy demonstrated that both claudins showed
      developmental stage- and segment-specific subcellular localizations in the
      epididymal epithelium. Claudin-2 was detected principally in the apical
      junctional region in the initial segment at postnatal day 7 and week 10 but lost
      its expression in all the distal segments including the caput, corpus, and cauda.
      Claudin-10 was detected principally in the apical junctional region in all
      segments on postnatal day 7 but only in the initial segment--especially along the
      entire lateral membrane--at 10 weeks. In freeze fracture electron microscopy,
      well-developed intramembranous particle strands were observed on the P face and
      complementary grooves with a few particles on the E face at 10 weeks. Many
      particles were occasionally observed on the grooves in the E face in the initial
      segment and distal caput. Tight junction strands were continuous and impermeable
      to lanthanum nitrate on postnatal day 7, suggesting the establishment of
      functional tight junctions. These segment-specific expressions of claudin-2 and 
      10 may contribute to creating the specific luminal fluid microenvironment which
      is necessary for the transport, maturation, and storage of spermatozoa.

PMID- 16276028
TI  - A framework for cancer surveillance in Japan.
AB  - The World Health Organization (WHO) has recommended that countries develop
      national cancer control programs in order to reduce the number of deaths due to
      preventable cancers. The national cancer control program should be comprehensive
      and systematic with evidence-based priority-setting and the efficient use of
      limited resources. In order to provide evidence-based information, cancer
      surveillance systems must be established with registration as a focus. Cancer
      registration monitors the incidence, mortality, survival, and prevalence of
      cancers. In Japan, however, cancer registration systems have not been either well
      developed or standardized until recently. In 2003, the Ministry of Health, Labour
      and Welfare of Japan launched the Third Term Comprehensive 10-Year Strategy
      Program for Cancer Control, which gave grants to several projects to enhance the
      dissemination and standardization of cancer registries. However, the
      establishment of a cancer registration system is merely the first step in the
      process to provide a comprehensive surveillance system that leads to a national
      cancer control program, as proposed by the WHO. To provide the best cancer care
      services equitably in Japan, cancer surveillance systems should be established
      without delay.

PMID- 16276029
TI  - Increased risk of obesity resulting from the interaction between high energy
      intake and the Trp64Arg polymorphism of the beta3-adrenergic receptor gene in
      healthy Japanese men.
AB  - BACKGROUND: Few studies have investigated the interaction between the Trp64Arg
      polymorphism of the beta3-adrenergic receptor gene (ADRB3) and environmental
      factors. This study aimed to investigate whether energy intake affects the
      relationship between this polymorphism and obesity. METHODS: Healthy Japanese men
      (n=295; age 46.1+/-11.5 years (mean +/-standard deviation); waist circumference
      83.9+/-9.3 cm; body mass index (BMI) 23.3+/-3.3 kg/m2) recruited in a Japanese
      chemical industry firm were eligible for analysis. Daily energy intake, protein,
      fat, and carbohydrate (PFC) ratio and daily physical activity were assessed by
      self-reported questionnaires. Genotyping for the polymorphism was performed with
      written informed consent. RESULTS: When the subjects were classified into two
      groups according to presence of the polymorphism, the groups were not
      significantly different in waist circumference or BMI. Quartile classification of
      energy intake, however, demonstrated a significantly larger ratio of obese
      subjects to non-obese subjects in the group with the polymorphism in the highest
      4th quartile alone. Multiple logistic regression analysis also revealed that the
      presence of the polymorphism increased the risk of obesity significantly in the
      4th quartile alone (adjusted odds ratio=3.37, 95% confidence interval=1.12-10.2).
      CONCLUSION: Presence of the polymorphism alone does not significantly increase
      the risk of obesity. However, high energy intake interacts with the polymorphism
      and leads to a significant increase in risk of obesity. The Trp64Arg polymorphism
      of ADRB3 warrants consideration, along with other polymorphisms involved in the
      development of obesity, for tailor-made prevention of obesity.

PMID- 16276030
TI  - Intake frequency of fish and serum levels of long-chain n-3 fatty acids: a cross
      sectional study within the Japan Collaborative Cohort Study.
AB  - BACKGROUND: Several investigations have adopted self-reported intake frequency of
      fish as a surrogate for intake of long-chain n-3 fatty acids, for which
      protective effects against cancer have been suggested. Whether reported fish
      consumption reflects the fatty acid intake, however, has to be elucidated.
      METHODS: We examined the association between intake frequency of fish and serum
      long-chain n-3 fatty acids (weight percentage of total fatty acids) among 1,257
      control subjects (631 men and 626 women), aged 40-79 years, in case-control
      studies nested in the Japan Collaborative Cohort Study. All the subjects were not
      fasting when blood was drawn. Serum fatty acids were determined by gas
      chromatography. RESULTS: In men, intake frequency of fresh fish and dried or
      salted fish was significantly but weakly correlated with serum levels of
      eicosapentaenoic (EPA), docosapentaenoic (n-3) (DPA), and docosahexaenoic (DHA)
      acids; the age-adjusted Spearman correlation coefficients ranged from 0.11 to
      0.18. In women, fresh fish consumption was somewhat associated with serum EPA
      (Spearman correlation coefficient = 0.12) as was dried or salted fish consumption
      with serum DPA (0.11). A rising trend in geometric means of serum EPA, DPA, and
      DHA was found with an increasing intake frequency of fresh or dried/salted fish
      in both sexes. The geometric means adjusted for age and participating institution
      in the highest intake category were higher than those in the lowest by 7% to 40%.
      CONCLUSIONS: A population with high self-reported frequency of fish intake, as a
      group, may have higher bioavailability of long-chain n-3 fatty acids than one
      with low frequency.

PMID- 16276031
TI  - Factors explaining disability-free life expectancy in Japan: the proportion of
      older workers, self-reported health status, and the number of public health
      nurses.
AB  - BACKGROUND: Disability-free life expectancy (DFLE) data for 47 prefectures in
      Japan were reported in 1999; however, few studies have identified the factors
      associated with the length of the DFLE. The objective of this study was to
      elucidate the primary factors that explain differences in DFLEs in Japan.
      METHODS: In our ecological study, 47 prefectures in Japan were used as units of
      analysis. The DFLEs for men and women at 65 years of age (DFLE65), calculated by
      Hashimoto et al using Sullivan's method, were set as dependent variables. From
      various national surveys, 181 factors associated with demographics, socioeconomic
      status, health status and health behaviors, medical environment, social
      relationships, climate, and other areas were gathered as independent variables.
      Pearson's or Spearman's correlation coefficients were calculated to screen
      independent variables potentially associated with the DFLE65s. Then, multivariate
      linear regression analyses were conducted for the selected 24 independent
      variables after adjusting for the proportion of older people (65 years or more)
      and population density. RESULTS: Multivariate linear regression analyses revealed
      that the large number of public health nurses per 100,000 population, a good self
      reported health status, and a high proportion of older workers were significantly
      associated with long DFLE65s for both genders. CONCLUSIONS: These three factors
      could potentially explain the differences in DFLE of the older population in
      Japan.

PMID- 16276032
TI  - Five-year stability of job characteristics scale scores among a Japanese working
      population.
AB  - BACKGROUND: The job characteristics scale of job strain, which combines high job
      demands and low decision latitude based on Karasek's model, has been applied to
      studies on health care and cardiovascular disease. However, little is known about
      the long-term stability of this scale with exposure of workers to job. We
      investigated the 5-year intraindividual variation in job characteristics scores
      among healthy community workers. METHODS: Subjects of the study were 458
      community dwelling persons forming part of the Jichi Medical School Cohort Study
      at Yamato (currently, Minami-Uonuma city), Niigata prefecture. The Japanese
      version of the World Health Organization Multinational Monitoring of Trends and
      Determinants in Cardiovascular Disease (WHO-MONICA) Psychosocial Study
      Questionnaire was implemented twice (from 1992 through 1995, and in 1999) to
      measure job demands and decision latitude levels. Intraclass correlation
      coefficients were computed to evaluate stability of scores of the questionnaire.
      RESULTS: Intraclass correlation coefficient of the decision latitude scores was
      0.629 (95% confidence interval: 0.564-0.686) and that of the job demands scores
      was 0.551 (0.476-0.617). Subgroup analyses by age, sex, education level, years
      since first employment, number of co-workers, and job category and status at
      baseline revealed similar results. In contrast, subjects who experienced position
      changes within the same enterprise or changed jobs showed lower correlation
      coefficients of both decision latitude and job demands scores compared to those
      who experienced no change in job contents. CONCLUSION: The Japanese version of
      the WHO-MONICA Psychosocial Study Questionnaire showed statistically significant
      long-term stability and could be to some extent responsive to change in job
      strain levels.

PMID- 16276033
TI  - Systematic evaluation and comparison of statistical tests for publication bias.
AB  - BACKGROUND: This study evaluates the statistical and discriminatory powers of
      three statistical test methods (Begg's, Egger's, and Macaskill's) to detect
      publication bias in meta-analyses. METHODS: The data sources were 130 reviews
      from the Cochrane Database of Systematic Reviews 2002 issue, which considered a
      binary endpoint and contained 10 or more individual studies. Funnel plots with
      observers'agreements were selected as a reference standard. We evaluated a trade
      off between sensitivity and specificity by varying cut-off p-values, power of
      statistical tests given fixed false positive rates, and area under the receiver
      operating characteristic curve. RESULTS: In 36 reviews, 733 original studies
      evaluated 2,874,006 subjects. The number of trials included in each ranged from
      10 to 70 (median 14.5). Given that the false positive rate was 0.1, the
      sensitivity of Egger's method was 0.93, and was larger than that of Begg's method
      (0.86) and Macaskill's method (0.43). The sensitivities of three statistical
      tests increased as the cut-off p-values increased without a substantial decrement
      of specificities. The area under the ROC curve of Egger's method was 0.955 (95%
      confidence interval, 0.889-1.000) and was not different from that of Begg's
      method (area=0.913, p=0.2302), but it was larger than that of Macaskill's method
      (area=0.719, p=0.0116). CONCLUSION: Egger's linear regression method and Begg's
      method had stronger statistical and discriminatory powers than Macaskill's method
      for detecting publication bias given the same type I error level. The power of
      these methods could be improved by increasing the cut-off p-value without a
      substantial increment of false positive rate.

PMID- 16276034
TI  - Association of pregnancy intention with parenting difficulty in Fukushima, Japan.
AB  - BACKGROUND: Our prior study revealed that nearly half of the Japanese women
      between the ages of 35 and 49 years experience an unintended pregnancy, many of
      which are carried to term. The present study is intended to investigate the
      association of the intention to become pregnant with parenting difficulty after
      birth. METHODS: We distributed self-administered questionnaires to mothers of 317
      randomly selected children aged 3 to 18 months who resided in Sukagawa City,
      Fukushima. The extent to which the unintended pregnancy is associated with the
      risk of negative attitude in parenting was examined by using multiple logistic
      regression analysis. RESULTS: The response rate was 69% and the proportion of
      births, the outcome of an unintended pregnancy, 22%. When the pregnancy was
      unintended, the mother may not deny her feelings toward child abuse (odds ratio
      [OR] = 5.2). She was unlikely to have discussion about child rearing with her
      husband (OR=3.1) or family (OR=3.3); or the husband rarely participate in child
      rearing (OR=1.9). CONCLUSION: To improve the child rearing environment, these
      findings provide preliminary evidence to underscore the importance of pregnancy
      planning and providing services to augment the parenting skills of couples who
      have an unintended pregnancy. A follow-up of pregnant women is currently underway
      to examine prospectively the effects on child rearing of one's intention to
      become pregnant.

PMID- 16276035
TI  - Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of
      expressions of intracellular adhesion molecule-1 and vascular endothelial growth
      factor in foam cells by a water-soluble fraction of Polygonum multiflorum.
AB  - Polygonum multiflorum stilbeneglycoside (PMS) is a water-soluble fraction of
      Polygonum multiflorum Thunb., one of the most famous tonic traditional Chinese
      medicines, that has protective effects on the cardiovascular system. The purpose
      of the present study is to elucidate the effects of PMS on macrophage-derived
      foam cell functions and the reduction of severity of atherosclerosis in
      hypercholesterolemic New Zealand White (NZW) rabbits. NZW rabbits were fed for 12
      weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet
      associated with irrigation with different doses of PMS (25, 50, or 100 mg/kg).
      Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS
      attenuated the increase in plasma cholesterol, low-density lipoprotein
      cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride.
      Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in
      atherosclerotic lesioned area ratio to total surface area, respectively. In U937
      foam cells, PMS could decrease the high expression of intercellular adhesion
      molecule (ICAM)-1 protein and the vascular endothelial growth factor (VEGF)
      protein levels in the medium induced by oxidized lipoprotein when analyzed by
      flow cytometry. The results proved that PMS is a powerful agent against
      atherosclerosis and that PMS action could possibly be through the inhibition of
      the expression of ICAM-1 and VEGF in foam cells.

PMID- 16276036
TI  - Increase in the deposition of aggregated protein in the glomeruli of
      spontaneously diabetic mice.
AB  - The aim of this study was to investigate the disposal of aggregated protein in
      the glomeruli of spontaneously diabetic mice. Diabetic mice, KK-A(y) and db/db,
      and age-matched ICR mice were injected intravenously with aggregated bovine serum
      albumin (a-BSA) at 0.6 mg/g, and the glomeruli and the blood were obtained.
      Diabetic mice had larger amounts of a-BSA in their glomeruli than the ICR mice,
      threefold in KK-A(y) and twofold in db/db, at 3 h after the a-BSA injection.
      Additionally, the disappearance of a-BSA was retarded in the diabetic glomeruli.
      KK-A(y) displayed a-BSA in the glomeruli 24 h after the a-BSA injection and db/db
      did after 12 h, while the ICR did by 8 h. In spite of increases of insulin to
      similar degrees in both strains of diabetic mice after the a-BSA injection, blood
      glucose levels markedly decreased in KK-A(y) compared with db/db. There were no
      histopathological alterations in the glomeruli of the diabetic mice. Depositions
      of a-BSA were confirmed to be higher in the diabetic glomeruli by the
      immunofluorescence technique, and KK-A(y) displayed higher depositions of a-BSA
      than did db/db. The present study suggests that hyperglycemia is involved in the
      increased deposition of aggregated protein in the glomeruli and that the
      degradation of aggregated protein is retarded in diabetic glomeruli.

PMID- 16276037
TI  - Effects of anti-nerve growth factor antibody on symptoms in the NC/Nga mouse, an
      atopic dermatitis model.
AB  - Nerve growth factor (NGF) is an important substance in the skin, where it can
      modulate nerve maintenance and repair. However, the direct link between NGF and
      pruritic disease such as atopic dermatitis is not yet fully understood. To
      determine whether NGF plays a major role in atopic dermatitis and in the
      development or maintenance of skin lesions, we performed a study using NC/Nga
      mice and compared mice with and without skin lesions. Our examinations of the
      NC/Nga mice sought to detect nerve fibers in the epidermis, measured serum and
      skin NGF content, and observed skin NGF by immunohistochemistry staining. We also
      examined the effects of anti-NGF antibody on dermatitis symptoms in NC/Nga mice.
      In these mice, nerve fibers were significantly increased in the epidermis of
      lesioned skin, and the NGF content of the serum and skin was significantly
      elevated. Anti-NGF antibodies significantly inhibited the development and
      proliferation of skin lesions and epidermal innervation and significantly
      inhibited any growth in scratching but did not ameliorate scratching already
      developed. Our findings suggest that NGF plays important roles in the
      pathogenesis of atopic dermatitis-like skin lesions and that inhibiting the
      physiological effects of NGF or suppressing increased NGF production may prevent
      or even moderate the symptoms of atopic dermatitis.

PMID- 16276038
TI  - Effect of maturation culture period of oocytes on the sex ratio of in vitro
      fertilized bovine embryos.
AB  - It has been suggested that the maturational stage of oocytes at time of
      insemination influences the sex ratio of resulting embryos. However, there are
      very few reports concerning the relationship between the maturation culture
      period of oocytes and the sex ratio of resulting embryos. The objective of this
      study was to investigate the effects of in vitro maturation culture period for
      bovine oocytes on the sex ratio of in vitro produced blastocysts using a novel
      technique of loop-mediated isothermal amplification (LAMP). Cumulus-oocyte
      complexes were collected from the ovaries of slaughtered cows, and then matured
      in vitro for various periods (16, 22, 28, and 34 h). After maturation culture for
      each period, the oocytes were inseminated with frozen-thawed spermatozoa, and
      then cultured in vitro. Blastocysts were harvested on Day 7 after insemination,
      and the sex of the embryos was examined using the LAMP method. The rates of
      oocytes matured to the metaphase II stage were significantly lower (P < 0.05) in
      the 16-h maturation group than in the other groups. The proportion of blastocyst
      formation after insemination was significantly higher (P < 0.05) in the 22-h
      maturation group than in the other groups. The proportion of male blastocysts
      increased with the increase in maturation culture period. The proportion of male
      blastocysts derived from oocytes matured for 34 h was significantly higher (P <
      0.05) than from oocytes matured for 16 and 22 h. These results indicate that the
      sex ratio of in vitro fertilized embryos is apparently influenced by the
      maturation culture period of the oocytes.

PMID- 16276039
TI  - In vitro and in vivo developmental ability of oocytes derived from porcine
      primordial follicles xenografted into nude mice.
AB  - We evaluated the developmental ability of oocytes in porcine primordial follicles
      xenografted into nude mice. Ovarian tissues from 20-day-old piglets, in which
      most of the follicles were primordial, were transplanted under the kidney
      capsules of ovariectomized nude mice. Forty-nine to 89 days after grafting (mean
      +/- SEM, 66.9 +/- 1.9 days; n = 64), the host mice showed the presence of
      cornified epithelial cells in their vaginal smears for the first time. The mice
      were then treated with 4 IU of equine chorionic gonadotropin (eCG) 60 days after
      first detection of vaginal cornification. Oocytes were collected from the host
      mice 48 h after treatment with eCG, and then matured. The maturation rates, based
      on the incidence of first polar body, ranged from 25.1% to 42.5%. They were then
      fertilized in vitro and cultured in vitro for 6 days, or transferred into estrous
      synchronized recipients and recovered after 6 days. On Day 6 of culture, 15.4% of
      the matured oocytes had cleaved to the 2- to 8-cell stage. However, neither the
      embryos cultured in vitro nor those transferred and recovered developed to
      advanced embryonic stages, such as morulae or blastocysts. This result suggests
      that the developmental ability of xenografted oocytes is insufficient, even after
      in vitro maturation. Further strategies, such as improvement of hormonal
      treatment for host mice, are required to enable oocytes in xenografted ovarian
      tissues to acquire the cytoplasmic maturation necessary for embryonic
      development.

PMID- 16276040
TI  - Basal body temperature method for detecting ovarian cycle in the Captive Beluga
      (Delphinapterus leucas).
AB  - The relationship between basal body temperature and circulating progesterone
      levels were investigated in a female beluga. Body temperature and serum
      concentrations of progesterone were measured daily and at 2-4 week intervals
      respectively, in a female beluga that was in captivity for 7 years between 1996
      and 2003. The beluga first ovulated in April, 2000 (13 years old). Thereafter,
      serum concentrations of progesterone showed cyclic changes, indicating that the
      ovulatory cycle had started. Serum concentrations of progesterone ranged from 0.1
      ng/ml to 15.7 ng/ml. Body temperature also showed cyclic changes during the
      estrous cycle. Body temperature ranged from 34.9 to 35.9 C, and tended to reach
      the peak during the high progesterone phase. Mating behavior was observed during
      the low body temperature phase. The changes in body temperature positively
      correlated with the circulating progesterone levels. The length of the estrous
      cycle was 36.7 +/- 3.9 (mean +/- SEM) days based on the intervals between the
      days of mating behavior. This is the first report demonstrating that body
      temperature clearly changes during the estrous cycle in a captive female beluga.
      The present finding suggests that measurement of body temperature is a useful
      method for detecting the ovarian cycle of the beluga in captivity.

PMID- 16276041
TI  - Phytoestrogens and their metabolites inhibit the sensitivity of the bovine corpus
      luteum to luteotropic factors.
AB  - The aim of this study was to examine whether active metabolites of phytoestrogens
      (equol and para-ethyl-phenol) inhibit sensitivity of bovine corpus luteum (CL) to
      luteinizing hormone (LH) and to auto/paracrine luteotropic factors (prostaglandin
      E2-PGE2 and prostaglandin F(2alpha)-PGF(2alpha)), and whether they influence
      pulsatile progesterone (P4) secretion by the bovine CL. In in vivo experiments,
      high levels of equol and para-ethyl-phenol were found in plasma and in the CL
      tissue of heifers and cows fed a soy bean diet (2.5 kg/animal/day), along with
      lower concentrations of P4 (P < 0.05). Both Prostaglandins (PG) and LH strongly
      stimulated P4 secretion in cultured pieces of CL that were collected from cows
      fed a standard diet (P < 0.01). There was no effect of PGs and LH on P4
      stimulation in CLs obtained from cows fed a diet rich in soy bean. Finally, we
      examined whether active metabolites of phytoestrogens participated in regulation
      of pulsatile P4 secretion and LH-stimulated P4 secretion in vitro using a
      microdialysis system. Equol and para-ethyl-phenol had no effect on basic and
      pulsatile P4 secretion in CLs during 240 min of perfusion when compared to the
      control (P < 0.05). However, they inhibited LH-stimulated P4 secretion (P <
      0.05). Phytoestrogens and their metabolites may disrupt CL function by inhibiting
      PG- and LH-stimulated P4 secretion.

PMID- 16276042
TI  - [Regulatory T cell and autoimmune diseases].
AB  - CD25+CD4+ regulatory T cells are naturally anergic and suppressive. They
      differentiate through thymus as professional regulator to control immunological
      self-tolerance in the periphery. When they are depleted from normal animals,
      various organ-specific autoimmune diseases spontaneously develop, and
      reconstitution of regulatory T cells prevents the diseases. Transcriptional
      factor FoxP3 is the master gene for differentiation and function of regulatory T
      cells. Mutation of FoxP3 gene causes development of autoimmune disease in both
      human and mouse. There are accumulating reports that regulatory T cells are
      abnormal in their number or function in several animal models and also patients
      with autoimmune diseases. These findings indicate that regulatory T cells are
      involved in the pathogenesis of many autoimmune diseases. Regulatory T cells can
      also be employed for the treatment of autoimmune diseases. Further studies of
      regulatory T cells, especially the detection of their specific markers and the
      development of the method to propagate them in an antigen-specific manner, will
      facilitate their clinical application.

PMID- 16276043
TI  - [B lymphocyte].
AB  - Recent studies have revealed that B cells play a critical role in autoimmunity
      and disease expression through various functions, including autoantibody
      production, cytokine secretion, antigen presentation, and co-stimulatory effect.
      Selective targeting of B cells has been recently achieved using a chimeric
      monoclonal antibody against CD20 (Rituximab). Significant clinical efficacy has
      been demonstrated in several autoimmune diseases including rheumatoid arthritis
      and systemic lupus erythematosus by the infusion of this antibody. Rituxumab
      significantly improves the symptoms during the long period of complete B cell
      depletion. Understanding the dynamics of B cell involvement in autoimmune
      diseases will be crucial to the development of B cell-targeted strategies.
      Conversely, the findings derived from studies of anti-B cell therapy provide us a
      lot of important clues to clarify the pathogenesis of autoimmune diseases. This
      review focuses on recent data demonstrating the roles of B cells in autoimmune
      diseases as well as the current studies concerning the treatment of autoimmune
      diseases by Rituximab.

PMID- 16276044
TI  - [Toll-like receptor].
AB  - Toll-like receptors (TLRs) have been revealed to recognize specific patterns of
      microbial components. Recognition of microbial components by TLRs initiates
      signal transduction pathways, triggering expression of genes, which products
      control innate immune responses and further instruct development of antigen
      specific acquired immunity. TIR domain-containing adaptors, such as MyD88, TIRAP,
      TRIF, and TRAM, play pivotal roles in TLR signaling pathways. Differential
      utilization of these TIR domain-containing adaptors provides specificity of
      individual TLR-mediated signaling pathways. TLR-mediated activation of innate
      immunity, when in excess, leads to immune disorders such as inflammatory bowel
      diseases. Therefore, several mechanisms that negatively control TLR signaling
      pathways and thereby prevent overactivation of innate immunity have been
      elucidated. Nuclear IkappaB proteins, such as Bcl-3 and IkappaBNS, have been
      revealed to be responsible for this process, by differentially inhibiting TLR
      dependent cytokine production.

PMID- 16276045
TI  - [Role of Fcgamma receptors in immune regulation and diseases].
AB  - The activation threshold of cells in the immune system is often tuned by cell
      surface molecules. The Fc receptors expressed on various hematopoietic cells
      constitute critical elements for activating or down-modulating immune responses
      and combines humoral and cell-mediated immunity. Thus, Fc receptors are the
      intelligent sensors of the immune status in the individual. However, impaired
      regulation by Fc receptors will lead to unresponsiveness or hyperreactivity to
      foreign as well as self antigens. Murine models for autoimmune disease indicate
      the indispensable roles of the inhibitory Fc receptor in the suppression of such
      disorders, whereas activating-type FcRs are crucial for the onset and
      exacerbation of the disease. The development of many autoimmune diseases in
      humans may be caused by impairment of the human Fc receptor regulatory system.
      This review is aimed at providing a current overview of the mechanism of Fc
      receptor-based immune regulation and the possible scenario of how immunological
      disorders might result from their dysfunction.

PMID- 16276046
TI  - [Involvement of semaphorins in autoimmunity].
AB  - Semaphorins were identified originally as guidance cues for developing axons.
      However, it is becoming clear that several semaphorins are crucially involved in
      the immune system. For instance, Sema4D (CD100) enhances activation of B cells
      and dendritic cells, and Sema4A is involved in T cell priming and Th1/Th2
      regulation. In addition, recent cumulative evidence reveals their importance in
      immunological homeostasis. We here focus on our current understanding of the
      roles of semaphorins in autoimmunity.

PMID- 16276047
TI  - [The role of BAFF in autoimmune diseases].
AB  - B cell activating factor belonging to the tumor necrosis factor family (BAFF) is
      a tumor necrosis factor (TNF) superfamily member best known for its role in the
      survival and maturation of B cells. BAFF is a ligand for three TNF receptor
      superfamily members: B-cell maturation antigen (BCMA), transmembrane activator
      and calcium-modulator and cyclophilin ligand interactor (TACI), and BAFF receptor
      (BAFF-R). Among them, BAFF-R plays the central role in the BAFF system, whereas
      TACI plays the inhibitory role. BAFF/BAFF receptors appear to span nearly all
      stages of B-lineage differentiation, ranging from the development, selection, and
      homeostasis of naive primary B cells to the maintenance of long-lived bone marrow
      plasma cells. Furthermore, excessive BAFF rescues self-reactive B cells from
      anergy, which may play a crucial role in the induction and development of
      autoimmunity. Mice overexpressing BAFF exhibit increased B cell numbers in spleen
      and lymph node and autoimmune phenotype similar to patients with systemic lupus
      erythematosus (SLE) and Sjogren's syndrome. Furthermore, inhibition of BAFF by
      TACI-Ig and BAFFR-Ig has been successful in treating murine models of SLE and
      rheumatoid arthritis. In humans, previous reports have shown elevated serum BAFF
      levels in SLE, rheumatoid arthritis, Sjogren's syndrome, and systemic sclerosis
      patients. Thus, the dysregulation of BAFF/BAFF receptor system may contribute to
      induction and development of autoimmune diseases and become one of important
      therapeutic targets.

PMID- 16276048
TI  - [Three cases of childhood-onset male systemic lupus erythematosus (SLE)
      successfully treated with a combination of pulse methylprednisolone and pulse
      cyclophosphamide].
AB  - We reported three cases of childhood-onset male systemic lupus erythematosus
      (SLE), all of whom successfully treated with a combination of pulse
      methylprednisolone (mPSL) and pulse cyclophosphamide (IVCY). All of them had
      severe lupus nephritis and were complicated with other collagen diseases. Two
      cases were complicated with Sjogren syndrome (SS) and the other was complicated
      with both SS and anti-phospholipid syndrome (APS). After a combination of pulse
      mPSL and IVCY for a year, followed by oral predonisolone (PSL) and azathioprine
      (AZA), following up renal biopsy were performed in all cases, which showed
      histological improvement in glomerulonephritis. One case had flares a year later,
      but no flares were observed either in clinical symptoms or in laboratory
      examinations in the others. Their autoantibodies except anti-nuclear antibody
      (ANA) were eliminated. We suggest a combination of pulse mPSL and IVCY is
      effective for the patients who are suffering with severe lupus nephritis
      complicated with the other collagen diseases.

PMID- 16276049
TI  - [A case of Mikulicz's disease complicated by autoimmune pancreatitis, in which
      impaired glucose tolerance was improved by glucocorticoid treatment].
AB  - A 73-year-old woman had experienced dry mouth and swellings of both upper eyelids
      from 1998. In October 2003, she also developed bilateral submandibular swellings,
      and was diagnosed with diabetes mellitus and prescribed antidiabetic medication.
      She consulted our hospital in the summer of 2004 due to the exacerbation of
      eyelid swelling, and was admitted in October 2004. Keratoconjunctivitis sicca was
      not present. CT and MRI of the head showed bilateral enlargement of the lacrimal
      and submandibular glands. Serological investigations revealed
      hypergammaglobulinemia, but as antinuclear antibody and anti-SS-A antibody were
      absent, further investigation was performed. Serum concentrations of IgG4 were
      elevated and biopsy of the minor salivary gland revealed a severe infiltration of
      IgG4-positive plasmacytes. The patient was therefore diagnosed with Mikulicz's
      disease. Abdominal CT demonstrated diffuse pancreatic swelling, and endoscopic
      retrograde cholangio-pancreatography revealed stricture of the common bile duct
      and main pancreatic duct, suggesting the complication of autoimmune pancreatitis.
      Treatment was commenced with 40 mg/day of prednisolone. This resulted in rapid
      resolution of the lacrimal and submandibular gland swellings and recovery of
      salivary gland function. Diffuse swelling of the pancreas and stricture of the
      common bile duct and main pancreatic duct also improved, and endogenous insulin
      secretion increased. Both Mikulicz's disease and autoimmune pancreatitis
      presented with elevated serum IgG4 and infiltration of IgG4-expressing plasma
      cells into the glandular tissues. We recently proposed the new diagnostic entity
      of "IgG4-related plasmacytic exocrinopathy"; however, if diabetes mellitus in
      autoimmune pancreatitis was caused by direct dysfunction of pancreatic cells, we
      must reconsider this pathogenesis and consider a wider concept including exocrine
      as well as endocrine glands. This case, in which both types of glands were
      affected, is therefore of considerable interest.

PMID- 16276050
TI  - Changes of magnetic resonance imaging on the brain in beagle dogs with aging.
AB  - Age-associated changes of magnetic resonance imaging (MRI) on the brain were
      evaluated in 19 beagle dogs aged from 8-month- to 16-year-old. A significant
      correlation of the volume of lateral ventricle space was observed in the dogs
      with age advanced, however, no correlation was found between hippocampus size and
      the aging. The hypo-intensity areas on T2-weighted MRI were detected in globus
      pallidus and substantia nigra with a significant correlation of both intensity
      ratios to lateral ventricle with age advanced. These areas were coincided with
      the accumulation of iron in the slice of the brain with Perls' staining. In
      addition, hyper-intensity area, suggesting perivascular demyelination with fluid
      filled space, was also observed in white matter surrounding the lateral ventricle
      on T2-weighted MRI. These results suggested that age-associated changes of T2
      weighted MRI were developed in the dog brain, especially in globus pallidus,
      substantia nigra, and white matter surrounding lateral ventricle, like as those
      reported in the human brain.

PMID- 16276051
TI  - Effects of exposure to a 50 Hz electric field on plasma levels of lactate,
      glucose, free Fatty acids, triglycerides and creatine phosphokinase activity in
      hind-limb ischemic rats.
AB  - We previously reported that extremely low frequency electric fields (ELF-EFs)
      affect energy metabolism in stressed conditions. To further confirm this, the
      effect of exposure to ELF-EFs on the experimental ischemic rat was examined. The
      test was based on a comparison of rats treated with EF alone, ischemic surgery
      alone, the combination of EF with ischemic surgery, or no treatment (double
      sham). The EF condition used in this study was an alternating current of 50 Hz EF
      at 17 500 V/m intensity for 15 min per day. The exposure to EF in ischemic rats
      significantly decreased plasma levels of free fatty acids and triglycerides,
      compared to those of the no treatment or EF alone group. The plasma lactate
      levels of two ischemic groups peaked on experimental day-4 and gradually
      decreased until the end of the study. The changes in the lactate levels induced
      by ischemia did not show any difference between rats treated with ischemia alone
      or a combination of ischemia with an EF. Any changes in plasma levels of glucose
      and creatine phosphokinase activity were not influenced by EF treatment. These
      results indicate that the EF effect on glycolysis parameters, plasma lactate or
      glucose levels, does not appear in a highly stressed condition and that EF
      effects varied dependent on the condition of organism but ELF-EF used in this
      study have impact on lipid metabolism parameter in a hind-limb ischemic rat.
      However, further studies are needed to elucidate the association of ELF-EF with
      the lipid metabolism system.

PMID- 16276052
TI  - Localization of aquaporin water channels in the airway of the musk shrew (Suncus
      murinus) and the rat.
AB  - Aquaporins (AQPs) constitute a family of water channels that facilitate membrane
      water permeability in various tissues of animals. In this study, we compared the
      expression and localization of AQPs in the respiratory system of the musk shrew
      (Suncus murinus), which is an insectivore, and the rat by immunohistochemical
      methods. In both the musk shrew and the rat, AQP1 was expressed throughout the
      airway in endothelial cells of subepithelial blood vessels and in nasal
      submucosal fibroblasts. AQP3 and AQP4 were detected in neither the epithelium nor
      the subepithelial layer of the musk shrew airway, but were abundant in the rat
      airway epithelium. Musk shrew AQP5 was distributed in the superficial epithelial
      cells facing the airspaces and in submucosal glandular cells, but, unlike in the
      rat, not in lung alveolar cells. Additionally, the expression patterns of AQP4
      and AQP5 of the musk shrew were partly similar to those of the human previously
      reported, absence of AQP4 and presence of AQP5 in the upper airway. The
      expression differences of AQPs between species in the airway indicate that the
      physiological importance of each AQP may be different in each species.

PMID- 16276053
TI  - Differences in tumor necrosis factor (TNF)alpha and TNF receptor-1-mediated
      intracellular signaling factors in normal, inflamed and scar-formed horse
      tendons.
AB  - Tumor necrosis factor (TNF) receptors (TNF-R)-mediated cell survival or apoptosis
      has been demonstrated in many cells, but little is known about survival or
      apoptotic signals via TNF-R1 in tendinocytes. In this study, we focused on four
      signaling factors, TNFalpha, TNF-R1, TNFR-associated factor2 (TRAF2) and caspase
      3, in order to elucidate the signaling events in tendinocytes. Samples were
      obtained from normal, inflamed and scar-formed equine superficial digital flexor
      tendons. To detect these signaling factors, samples were subjected to
      immunohistochemistry and Western blot analysis, and some samples were also
      subjected to reverse transcription-polymerase chain reaction (RT-PCR), PCR
      Southern blot analysis and in situ hybridization to detect the expression of
      TNFalpha mRNA. Distribution of the four factors differed depending on the tendon
      condition, normal, inflamed or scar-formed. In the normal tendon, large amounts
      of TRAF2 were found in tendinocytes, but the amounts of TNF-R1 were small.
      TNFalpha mRNA was expressed most highly in the inflamed tendon. TNF-R1, which was
      only faintly detected in the normal tendon, was detected at a high level in the
      inflamed tendon, and the amounts of TRAF2 and caspase-3 also increased. Activated
      caspase-3 was only detected in the inflamed tendon. TNFalpha mRNA was also
      expressed in the scar-formed tendon, though it showed weak signals, and the
      expression levels of TNF-R1, TRAF2 and caspase-3 proteins were very low. Two
      distinct intracellular signaling pathways of TNFalpha, which lead to cell
      survival and apoptosis, might be present in tendinocytes mediated through TNF-R1.
      These results, which reflect the dynamism of TNFalpha, provide important clues
      for means to prevent tendinopathy.

PMID- 16276054
TI  - Use of 13C-acetate breath test for assessment of gastric emptying in horses.
AB  - This study aimed to establish and standardize a breath test that uses 13C-acetate
      in a liquid diet for evaluation of gastric emptying in horses. Seven adult
      healthy thoroughbreds were used in this study. They were given 13C-acetate (125
      mg, 250 mg, or 500 mg) in a test meal (2000 ml liquid diet) via an intranasal
      catheter. 13C concentrations in the exhaled CO2 were measured in samples taken
      before and after test meal administration using an infrared absorption
      spectroscope. In the 500 mg 13C-acetate group, Delta13CO2 showed a steep gradient
      immediately after meal administration compared to the 125 mg and 250 mg groups.
      Therefore, t(max) in the 500 mg group was easier to determine than in the 125 mg
      and 250 mg groups. In the 500 mg group, GEC, half-empty time (t1/2), calculated
      t(max) (t(lag)), and t(max) were 1.95 +/- 0.28 (mean +/- SD), 229.2 +/- 57.0
      (min), 139.2 +/- 22.2 (min), and 124.0 +/- 28.4, respectively. Differences in CV
      observed in the 500 mg group were lower than those in the 125 mg and 250 mg
      groups. This study demonstrates that the 13C-acetate breath test is useful for
      evaluating gastric emptying in horses since it is non-invasive and does not
      require set up of special facilities or equipment. Optimum evaluation of gastric
      emptying in horses can be achieved with 500 mg of 13C-acetate given in a liquid
      diet.

PMID- 16276055
TI  - Antimicrobial susceptibility of pathogenic Escherichia coli isolated from sick
      cattle and pigs in Japan.
AB  - We examined the 12 antimicrobial susceptibilities of 175 E. coli isolates from
      sick cattle and pigs by an agar dilution method. Resistance was found in 78.3% of
      isolates for oxytetracycline, 70.3% of isolates for dihydrostreptomycin, and
      49.1% of isolates for ampicillin. When compared with healthy animals reported by
      Kijima-Tanaka et al., resistance rates for 11 antimicrobial agents were higher in
      sick cattle than in healthy cattle, and resistance rates for all antimicrobial
      agents were higher in sick pigs than in healthy pigs. Comparing cattle and pigs,
      resistance rates to colistin was higher in porcine isolates than in bovine
      isolates, but was lower in porcine isolates than in bovine isolates for
      cefazolin. With regard to the association of virulence factors, higher resistance
      rates to colistin and enrofloxacin were observed in STEC (61 strains) than in non
      STEC (57 strains) among porcine isolates, while there were no significant
      differences in bovine isolates. In conclusion, these results can be considered
      helpful for adequate selection and prudent use of antimicrobial agents for
      several types of colibacillosis.

PMID- 16276057
TI  - Analysis of genetic variations in the exon 27 region of the canine BRCA2 locus.
AB  - Mammary tumors are the most common tumor type in women as well as in female dogs.
      The BRCA2 gene encodes a large nuclear protein that is involved in DNA repair,
      and mutations in the human BRCA2 confer an increased risk of female mammary
      tumors. The BRCA2 protein acts as a tumor suppressor, and inactivation of BRCA2
      by loss of heterozygosity is implicated in mammary carcinogenesis. In this study,
      to establish an appropriate polymorphic marker for loss of heterozygosity
      analysis of the canine BRCA2, we analyzed the genomic sequences of the exon 27
      regions of 30 mammary-tumor-bearing and 21 tumor-free dogs. In addition to
      10204ins/delAAA, which is the only polymorphism previously identified for the
      canine BRCA2 locus, we discovered four novel single nucleotide polymorphisms. The
      analysis of these five polymorphisms revealed the presence of four allele types.
      Since 10204ins/delAAA was the most common of the five polymorphisms identified,
      we developed a PCR-based assay method to assay for this polymorphism. We believe
      that this method is valuable for loss of heterozygosity analysis of the canine
      BRCA2 gene in tumor pathogenesis.

PMID- 16276056
TI  - Therapeutic effect of modified oligopeptides from the beetle Allomyrina dichotoma
      on methicillin-resistant Staphylococcus aureus (MRSA) infection in mice.
AB  - Anti-bacterial activity of two synthesized oligopeptides, RLYLRIGRR-NH2 (peptide
      A) and RLRLRIGRR-NH2 (peptide B), both which based on a putative active site of
      defensin, an anti-bacterial peptide from the beetle Allomyrina dichotoma, was
      examined by macroscopic and histopathologic assessment during the course of
      infection in mice inoculated with methicillin-resistant Staphylococcus aureus
      (MRSA) in vivo. Both peptides A and B decreased the mortality of mice inoculated
      with MRSA. Peptides A and B decreased the macroscopical and histopathological
      lesions by MRSA infection in mice even seven days after the challenge. The anti
      bacterial activity of peptides A and B has a therapeutic effect on MRSA infection
      in mice even seven days after being challenged.

PMID- 16276058
TI  - Carcinogenicity and chronic toxicity in mice and rats exposed by inhalation to
      para-dichlorobenzene for two years.
AB  - Carcinogenicity and chronic toxicity of para-dichlorobenzene (p-DCB) were
      examined by exposing 50 BDF1 mice and 50 F344 rats of both sexes by inhalation to
      p-DCB vapor at a target concentration of 0 (control), 20, 75 or 300 ppm for 6
      hr/day, 5 days/week and 2 years. Incidences of hepatocellular carcinomas,
      hepatoblastomas and hepatic histiocytic sarcomas in the 300 ppm-exposed male
      mice, and hepatocellular adenomas and carcinomas and hepatoblastomas in the 300
      ppm-exposed female mice were increased. An increase in the incidences of most of
      those liver tumors was dose-related. No increase in tumor incidence was found in
      any p-DCB-exposed rat of either sex. Centrilobular hypertrophy of hepatocytes and
      papillary mineralization and pelvic urothelial hyperplasia of the kidney were
      noted in the 300 ppm-exposed male rats. Treatment- and age-related increases in
      incidences of the eosinophilic globules of the respiratory and olfactory
      epithelia in female rats and incidences of the respiratory metaplasia of the
      nasal gland epithelium in mice and rats and the olfactory epithelium in mice were
      noted. The nasal lesion was the most sensitive endpoint of chronic inhalation
      toxicity. Induction of the mouse hepatocarcinogenicity and lack of the rat
      nephrocarcinogenicity found in the present study were compared with the mouse
      liver tumors and the rat renal tumors reported by the NTP gavage study, and
      discussed in light of the estimated p-DCB uptake into the body through the
      inhalation and the oral administration.

PMID- 16276059
TI  - Onset and duration of luteal activity postpartum and their effect on first
      insemination conception rate in lactating dairy cows.
AB  - The incidence of different types of luteal activity postpartum and their effect
      on reproductive performance were studied in 21 postpartum dairy cows.
      Progesterone concentrations in defatted milk collected 3 times a week were
      determined by EIA. Reproductive tract examination was undertaken every other week
      postpartum. Body weight and body condition score (BCS) were measured before and
      after calving and the average 100-day milk yield was calculated. Nine (42.9%)
      cows had normal ovarian activity (first luteal activity < or = 50 days postpartum
      followed by regular cycles), 5 (23.8%) had prolonged luteal phase (PLP; ovarian
      cycle with luteal activity > or = 20 days pre-service) and in 7 (33.3%) cows the
      first luteal activity was shown later than 50 days postpartum (DOV). When
      compared with normal cows, both PLP and DOV had longer interval to first
      insemination (63.1 +/- 22.0 days versus 77.6 +/- 21.6 and 93.0 +/- 22.3 days,
      P<0.05 and P<0.01, respectively), lower first insemination conception rate (88.9%
      versus 0.0% and 57.1%, P<0.01 and P<0.05, respectively) and greater BCS loss
      (0.81 +/- 0.2 versus 1.05 +/- 0.21 and 1.04 +/- 0.10, respectively, P<0.01). Cows
      with PLP showed longer interval to uterine involution than normal and DOV groups
      (54.0 +/- 8.3 days versus 42.4 +/- 5.5 and 43.3 +/- 8.3 days, respectively,
      P<0.01) and higher 100-day milk yield (38.8 +/- 2.7 kg versus 33.6 +/- 4.7 and
      29.9 +/- 6.1 kg, respectively, P<0.01). In conclusion, more than half of the cows
      had abnormal luteal activity postpartum, which adversely affected reproductive
      performance.

PMID- 16276060
TI  - Quantitative analysis of Staphylococcus aureus in skimmed milk powder by real
      time PCR.
AB  - A large-scale outbreak of food poisoning caused by consumption of skimmed milk
      powder contaminated with staphylococcal enterotoxin A (SEA) occurred in Japan. No
      viable Staphylococcus aureus was detected in the skimmed milk powder, however,
      sea and nuc genes of S. aureus were detected in it by PCR. The number of S.
      aureus in skimmed milk powder was estimated by quantitative real-time PCR.

PMID- 16276061
TI  - Infiltrative lipoma in cervical bones in a dog.
AB  - A 4-year-old, neutered male Maltese presented with a 2-month history of right
      hemiparesis. The radiographic findings revealed bone lysis, and sclerotic changes
      in the right section of the fifth and sixth cervical bones with a mild
      radiolucent mass around the lesion. The magnetic resonance imaging revealed a
      hyperintense mass located in the region extending from the muscles to the bones
      and compressing the spinal cord. The mass was removed via a hemilaminectomy in
      the cervical area using the ventral and dorsal approach, and a histological
      examination confirmed that it was adipose tissue. An infiltrative lipoma was
      diagnosed based on these findings. The dog has ambulated normally for 24 months
      since undergoing surgery.

PMID- 16276062
TI  - The effect of thrombin on astrocyte stellation with regional specificity.
AB  - In this study, we have examined the possible existence of astrocyte regional
      heterogeneity in thrombin effect on astrocyte stellation. Neonatal astrocytes
      were cultured for 2 weeks from six different regions of the neonatal rat brain,
      including the cerebral cortex, hippocampus, brainstem, midbrain, hypothalamus and
      cerebellum. Culture medium was changed to DMEM containing 8-CPT-cyclic AMP (cAMP)
      or isoproterenol plus various concentrations of thrombin for 2 hr. Thrombin
      effectively blocked both cAMP- and isoproterenol-induced cell stellation in a
      dose-dependent manner in all regional astrocytes except cerebellar astrocytes. RT
      PCR analysis showed that thrombin receptor mRNA was expressed in all regional
      astrocytes, suggesting that cerebellar astrocytes may maintain a unique signaling
      pathway downstream of the thrombin receptor.

PMID- 16276063
TI  - Hepatocellular toxicosis associated with the alternate administration of
      carprofen and meloxicam in a siberian husky.
AB  - A 4-year-old female Siberian Husky was diagnosed with pyogranulomatous steatitis
      at the site of a recurrence of left anal sac rupture (day 1). Carprofen and
      orbifloxacin were given for 13 days without improvement. A single dose of
      meloxicam was administered prior to surgical resection of the anal sac, and based
      on elevated liver enzyme activity, liver supportive therapy was initiated. The
      dog received carprofen and orbifloxacin orally on the evening of day 14. The dog
      became anorectic the following morning, and began vomiting. Despite supportive
      therapy, the dog was unresponsive to treatment and died on day 16. Postmortem
      examination revealed severe vacuolar change and acute necrosis of hepatocytes
      consistent with carprofen and meloxicam induced-toxicosis.

PMID- 16276064
TI  - Microsatellite polymorphism in Japanese mongrel dogs.
AB  - The genetic variability of 182 unrelated mongrel dogs living in various areas of
      Japan (from Hokkaido to Okinawa) was studied by collecting their blood. Ten
      microsatellite loci were chosen from different autosomal chromosomes. After
      combining a few rare adjoining alleles to allelic classes, it was confirmed that
      the Hardy-Weinberg equilibrium was attained in each locus. The polymorphic
      information contents (PICs) of the loci, Ren37A11, Ren48E01, AHTk253, ZuBeCa30,
      Ren277K09, Ren42N13, AHT130, PEZ03, PEZ12, and AHT121, were 0.58, 0.63, 0.67,
      0.67, 0.68, 0.71, 0.79, 0.80, 0.80, and 0.80, and the power of discriminations
      (PDs) were 0.80, 0.85, 0.87, 0.88, 0.88, 0.89, 0.94, 0.94, 0.94, and 0.94,
      respectively. The combined mean exclusion chance (MEC) was 0.9995, indicating
      that these microsatellite loci are useful for kinship testing of Japanese dogs.

PMID- 16276066
TI  - Alleviative effects of gamma-aminobutyric acid (GABA) on behavioral abnormalities
      in aged dogs.
AB  - gamma-aminobutyric acid (GABA, 30 mg/kg) was administered to aged dogs with
      recent history of veterinary clinic visits (mean age: 15.3 years old) once daily
      for 2 weeks by mixing with food. Their owners subjectively evaluated the effects
      of GABA on behavioral signs often associated with aging in the dogs. Improvement
      in some of behavioral signs was notable without any observable adverse effects.
      Dogs administered with GABA tended to exhibit improvement in emotional states and
      signs may be caused by neurovegetable dysfunction, though effects on cognitive
      dysfunction syndrome were not always observed. Thus, GABA administration may be
      one of the effective means of improving the quality of life of aged dogs.

PMID- 16276065
TI  - Cloning and expression of canine interferon-alpha genes in Escherichia coli.
AB  - We cloned five new subtypes of cDNA encoding canine interferon-alpha (CaIFN
      alpha) from a canine epithelial cell line. CaIFN-alphas were divided into two
      groups by amino acid sequences and a molecular phylogenic tree. Two subtypes of
      them were expressed in Escherichia coli, and IFN proteins were purified.
      Recombinant CaIFN-alphas were highly species-specific and showed antiviral
      activity against Vesicular stomatitis New Jersey virus and canine adenovirus-1 ,
      but not against canine herpesvirus-1.

PMID- 16276067
TI  - A neurological disease with spongy degeneration in a newborn Japanese black calf.
AB  - A Japanese Black calf, 3 day-old male, showed severe ataxia, lateral recumbency,
      and opisthotonos at the birth. Histopathological examinations revealed severe
      status spongiosis throughout the central nervous system. Numerous vacuoles within
      the neuropile varying in size and shape were observed in both formalin-fixed
      paraffin and cryostat sections. In the lesions, a limited number of spheroids and
      macrophages were observed within the myelin sheaths with very mild astrogliosis.
      These vacuoles were negative for both periodic acid Schiff and Sudan black
      stains. The clinical and histopathological features were almost in conformity
      with those of bovine maple syrup urine disease (MSUD). Although we could not
      confirm completely the etiology, congenital hereditary neurological diseases
      including MSUD are considerable as the possible disease entry in the present
      case.

PMID- 16276068
TI  - Scanning electron microscopic study on the microarchitecture of the vascular
      system in the pigeon lung.
AB  - The resin casts of the respiratory and vascular systems in pigeon lung were
      examined using a scanning electron microscope. The primary bronchi branched to
      form many secondary bronchi that anastomosed with each other via the parabronchi.
      Numerous infundibula protruded from the parabronchi via the atria and ramified
      into the air capillaries. The pulmonary artery entered into the lung and branched
      into three vessels that coursed the interparabronchial parts. The
      intraparabronchial arterioles penetrated the gas-exchange tissue to form the
      anastomosing networks of blood capillaries. The observation of the double casts
      of the respiratory and vascular systems revealed three-dimensional complicated
      networks of air capillaries and blood capillaries.

PMID- 16276069
TI  - Cloning of cDNA encoding canine endothelin receptors and their expressions in
      normal tissues.
AB  - The receptors for endothelin (ET) family, ETA and ETB, were molecularly cloned
      and the expression of ETA and ETB as well as preproendothelin-1 (PPET-1,
      precursor of ET-1) was examined in normal canine tissues by RT-PCR. The entire
      open reading frames of the canine ETA and ETB were shown to encode 427 and 442
      amino acid residues, respectively, showing from 87.4 to 97.3% sequence similarity
      to human, mouse, and rat counterparts. ETA and ETB mRNAs were ubiquitously
      expressed in a variety of canine tissues in this study and PPET-1 mRNA was
      detected in the tissues except for heart and liver. It was speculated that ET
      could play an important role in physiological events in most of the organs.

PMID- 16276070
TI  - Epidemiological association between some dietary habits and the increasing
      incidence of type 1 diabetes worldwide.
AB  - BACKGROUND/AIMS: The variation in incidence of type 1 diabetes (T1D) worldwide is
      genetically based. However, its increasing incidence is environmentally
      determined. Our aim was to describe the role of nutritional habits and of gene
      nutrient interactions in the rising incidence of TID. METHODS: We did an
      ecological study in the 37 world areas were a 3% yearly increase of T1D incidence
      had been reported, and we calculated through the FAO's Food Balance Sheets the
      per caput daily supply of milk, meat and cereals from 1961 to 2000 and its
      correlation with the TID incidence. RESULTS: The supply of milk and cereals
      remained almost unchanged, whereas that of meat increased by over 31%. The
      absolute mean TID increase (number of cases per 100,000 per year) was + 0.32. A
      significant positive correlation with supply of milk was present from 1961 to
      2000, while that with meat and cereals became significant in 1983 and 2000.
      CONCLUSION: Our ecological analysis indicates that nutritional factors, and in
      particular meat consumption, play a role in the incidence of T1D and its increase
      worldwide. Further experimental and case-control studies are warranted in order
      to assess the gene-nutrient interactions.

PMID- 16276071
TI  - Effect of a Mediterranean meal on postprandial carotenoids, paraoxonase activity
      and C-reactive protein levels.
AB  - BACKGROUND AND AIM: Atherosclerosis involves oxidative and inflammatory mediators
      regulated by fat and antioxidants. Therefore, we studied the postprandial
      evolution of plasma lipids, carotenoids, C-reactive protein (CRP), and human
      serum paraoxanase activity (PON1) following two different fatty meals. SUBJECTS
      AND METHODS: Eight healthy males consumed a 45% fat 1,000 Kcal Mediterranean-like
      (Med) meal (monounsaturated 61% of fat) compared to a Western-like (Wes)
      (saturated 57% of fat) meal. Blood was collected at baseline (time 0) 2, 4 and 7
      h postprandial. Plasma lipids, glucose, insulin, total carotenoids, CRP, and PON1
      were analyzed. RESULTS: There was a marginal increase in cholesterol and glucose
      after both meals. Triglycerides increased modestly (to less than 200 mg/dl) and
      insulin increased (more in the Wes-like meal) but still within normal range,
      indicating a low glycemic index for both meals. Only the Med-like meal resulted
      in a significant increase in both PON1 activity (16%, p < 0.02) and carotenoids
      (74%, p < 0.02) with a 2-hour postprandial decrease in CRP (6%, p < 0.02).
      CONCLUSION: A postprandial monounsaturated fatty acid rich meal increases both
      plasma carotenoids and PON1 with a decrease in CRP levels, thus providing a novel
      potential explanation to the protective properties of a Mediterranean diet
      against atherogenesis.

PMID- 16276072
TI  - Heat processing in infant formulas induces changes in copper tissue levels in
      suckling and weanling rats.
AB  - AIM: To assess the effects of dehydration, conventional in-bottle sterilization,
      and ultrahigh-temperature (UHT) sterilization, involved in the production of
      infant formulas, on the copper bioavailability in rats at two stages. METHODS:
      Two-week-old suckling rats were fed a reconstituted powder (P1) and an in-bottle
      sterilized liquid infant formula (SC1) in a drinking bottle for 7 days. Weanling
      rats were fed P1, SC1, another powder (P2), and a liquid UHT formula (UHT2)
      complemented with a standard rat diet. Intake, body weight, and percentage copper
      absorption were calculated, and whole-body, serum, liver, skin, and erythrocyte
      copper concentrations were determined. RESULTS: Food intake, body weight, and
      copper intake were reduced in suckling rats consuming SC1, but the percentage
      copper absorption increased, and whole-body and tissue copper concentrations were
      unaffected, except for the erythrocyte copper concentration which was
      significantly higher as compared with pups fed P1. In weanling rats, the only
      difference observed was the significantly higher liver copper concentration in
      animals fed the diet containing P1 as compared with the diets containing SC1 and
      UHT2. CONCLUSIONS: Consuming the SC1 formula induced high erythrocyte copper
      levels in suckling rats, whereas the equivalent dehydrated formula (P1) induced
      elevated liver copper concentrations in weanling rats. This is associated with
      the different Maillard reaction products resulting from the processing of each
      infant formula and with the developmental stage of the animals.

PMID- 16276073
TI  - Visceral adiposity and apolipoprotein C-III in apolipoprotein B-containing
      lipoproteins are independent predictors in determining atherogenic lipid
      profiles.
AB  - BACKGROUND/AIMS: Little is known about how visceral adiposity and apolipoprotein
      CIII in apoB-containing lipoproteins influence atherogenic lipids profiles. The
      purpose of this study was to determine the relationships of visceral adiposity
      and apoC-III in apoB-containing lipoproteins (LpB:C-III) with lipoprotein lipids
      in circulating plasma. METHODS: A subgroup of 46 men (n = 20, aged 29.1-33.4
      years) and women (n = 26, aged 29.1-33.8 years) were recruited from an ongoing
      population study at our institution. Anthropometric variables including weight,
      height, and waist circumference were measured using standard procedures, and body
      mass index was calculated (kg/m(2)). Visceral adipose tissue (VAT) was measured
      with magnetic resonance imaging. Plasma apolipoproteins, lipids, glucose, and
      insulin were measured after an overnight fasting. RESULTS: The men had a
      significantly higher waist circumference, glucose, and TC/HDL-C ratio, while the
      women had a significantly higher HDL-C and apoA-I. In particular, this is the
      first study to report that VAT and LpB:C-III were independent predictors in
      determining plasma triglyceride concentrations. CONCLUSION: The relations of
      plasma triglyceride concentration with VAT and LpB:C-III suggest that information
      on VAT and apoC-III in apoB-containing lipoproteins may provide additional
      information on the atherogenic lipid profiles.

PMID- 16276075
TI  - Nutritional differences between elderly men and women. Primary care evaluation in
      Hungary.
AB  - BACKGROUND: Many differences exist between the two genders, i.e., biological,
      sociological, and also behavioral, which often depend on age. OBJECTIVES: The aim
      of this study was to find characteristic differences between nutritional habits
      of elderly men and women. METHODS: 266 elderly people (109 men >65 years, and 157
      women >60 years) were consecutively selected from primary care patients, in
      Budapest, Hungary. A self-managed questionnaire was filled in on lifestyle and
      eating habits, including a food frequency questionnaire. Medical check-up,
      registration of anthropometrical parameters, and laboratory tests were also
      performed. 53 subjects were also involved in a 3-day dietary recall. RESULTS: The
      meal frequency was increased during aging in both genders, especially in men.
      Lunch was preferred by most of the women as a principal meal, but one quarter of
      the men had a filling dinner instead of lunch. Alcoholic beverages were consumed
      more and frequently by men. The fluid intake was low, especially in women. Milk
      and diary products, fresh fruit, bread, biscuits, chocolate, coffee and vitamin
      supplements were consumed more frequently by women. Almost all types of meat,
      eggs, and vegetables were more preferred by men and their energy intake was also
      higher (9.75 vs. 8.78 MJ). In both genders, fat represented a higher ratio (39%)
      of energy intake than recommended. The increase of body weight from youth to
      elderly was greater in women (14.04 vs. 10.65 kg). Prices had a higher impact on
      food purchases by women. CONCLUSION: High energy intake over decades led to
      overweight in both genders (BMI >27 kg/m(2)). It seemed that the eating habits
      and food choices of women were closer to healthy ones and recent recommendations,
      although due to metabolic reasons and to the lower energy expenditure, they
      gained more weight. The elderly are the target population on every level of
      medical care. Further evaluations are needed to determine the differences in
      nutrition and to promote better administration of drugs and to establish public
      health suggestions.

PMID- 16276074
TI  - Endogenous hypertriglyceridemia intensifies the course of cerulein-induced
      pancreatitis in rat: relation with changes in the VLDL composition.
AB  - AIMS: To study if the course of cerulein-induced pancreatitis in rats changes in
      a state of triglyceride-rich lipoprotein metabolism alteration. METHODS: Two
      groups of rats received control diet during a 90-day period (A) and sucrose-rich
      diet to induce endogenous hypertriglyceridemia (B). Subgroups A2 and B2 received
      i.p. 45 microg cerulein/kg body weight (to induce acute pancreatitis).
      Histological examination of pancreas tissue, serum pancreatic lipase, lipoprotein
      profile and VLDL chemical composition were assessed. Then, pancreatic lipase
      hydrolytic activity on VLDL-triglycerides was evaluated in vitro. RESULTS:
      Cellular vacuolization was observed in all of the cerulein-injected rats, but
      only in subgroup B2 fat necrosis was present. Serum triglycerides were higher in
      subgroup B1 than in subgroup A1 (mean +/- SEM, mg/dl 123,77 +/- 25.7 vs. 65.8 +/-
      7, p < 0.01). Triglycerides from rats fed with sucrose-rich diet, decreased after
      cerulein-induced pancreatitis (80.38 +/- 11.3 vs. 123,77 +/- 25.7, p < 0.02).
      Moreover, the endogenous hypertriglyceridemic rats showed an increment of VLDL
      triglyceride content, which decreased when rats were injected with cerulein. A
      negative correlation was found between VLDL-triglyceride content and serum
      pancreatic lipase activity (r = 0.58, p < 0.02). The in vitro assay showed a
      decrease in VLDL-triglyceride content post incubation with pancreatic lipase
      enriched serum (mean +/- SD: 59.2 +/- 27.7%, p < 0.01). CONCLUSIONS: The
      endogenous hypertriglyceridemia intensifies the course of cerulein-induced
      pancreatitis and it could be related to the decrease in VLDL-triglycerides as a
      consequence of pancreatic lipase hydrolytic activity.

PMID- 16276076
TI  - Assessment of aqueous humor zinc status in human age-related cataract.
AB  - Age-related cataract is an ever-increasing health problem among the elderly
      population worldwide. In recent years, there has been speculation that the levels
      of micronutrients in ocular tissue may play a role in the pathogenesis of
      cataract, especially zinc, since it is found in high concentrations in the eye
      tissues, including the aqueous humor. 44 subjects diagnosed with cataract were
      chosen for study and matched with 21 healthy controls to determine the
      concentration of zinc in aqueous humor. The findings revealed that a
      significantly higher concentration of zinc was present in the aqueous humor of
      our study population compared to controls (p < 0.001). These findings, in
      agreement with several previous studies, amplify the need for further
      investigation to determine if these higher levels are in actuality a consequence
      of the disease or a factor in the formation of cataract.

PMID- 16276078
TI  - Interpretation of cardiac troponin measurements in neonates--the devil is in the
      details. Commentary to trevisanuto et Al.: cardiac troponin I in asphyxiated
      neonates (biol neonate 2006;89:190-193).

PMID- 16276077
TI  - Effect of olive oil-fried sardine consumption on cholesterol content in the
      serum, lipoproteins, spleen and adipose tissue of hypercholesterolemic rats.
AB  - BACKGROUND: The information about the effect of fried-oily fish consumption on
      cholesterol metabolism is rather scarce. AIM: To test the effect of olive oil
      fried sardine consumption on cholesterol content in the serum, lipoproteins,
      spleen and adipose tissue of hypercholesterolemic rats. METHODS:
      Hypercholesterolemia was induced for 3 weeks by a casein + olive diet containing
      cholesterol and bovine bile (COC). Rats were later switched for 2 weeks to diets
      containing casein + olive oil (CO), olive oil-fried sardines (S), and olive oil
      fried sardines-cholesterol-bovine bile (SC) while one rat group continued on the
      COC diet. Cholesterol was determined in serum, lipoproteins, adipose tissue and
      spleen. RESULTS: The SC diet markedly blocked the hypercholesterolemic induction
      of the cholesterol-raising agents. Dietary cholesterol withdrawal decreased serum
      cholesterol levels, with the S diet inducing the highest decrease in serum and
      VLDL + LDL-cholesterol levels. Cholesterol withdrawal decreased spleen total
      cholesterol content and weight but the S diet was unable to reduce spleen
      cholesterol content (micromol/g) more than CO diet. Adipose tissue of S rats
      displayed the lowest cholesterol values. Cholesterol (mmol/g) of adipose tissue
      correlated very significantly with total serum cholesterol (r = 0.9225, p <
      0.0001) and VLDL + LDL-cholesterol (r = 0.9313, p < 0.0001). CONCLUSIONS:
      Cholesterol in adipose tissue was very sensitive to variations in plasma
      cholesterol. Consumption of fried sardines interacts with cholesterol withdrawal,
      accelerating serum cholesterol normalization and reduction of cholesterol levels
      in adipose tissue.

PMID- 16276079
TI  - The metabolic syndrome and type 2 diabetes: epidemiological figures and country
      specificities.
AB  - Over the last 20 years, the prevalence of the metabolic syndrome has steadily
      increased in all populations worldwide, changing slowly the phenotype of the
      human race and potentially our concept of physiological normality. Our affluent
      phenotype reflects progressive adaptation to the external environment, which in
      turn changes the standards of the metabolic variables such as body weight, blood
      pressure, lipid values and glucose homeostasis. The human survivors of the
      difficult times of the hunter-gatherer period have probably benefited from genes
      which have allowed for more efficient food utilization, fat deposition and weight
      gain, a concept referred to as the 'thrifty gene' hypothesis. This genetic
      background has now become detrimental in our society of high energy consumption,
      little physical activity and lifestyles that favour stress and anxiety. These
      genetic and environmental interactions explain the explosion in the prevalence of
      the metabolic syndrome and diabetes. If future estimates for the number of
      patients with diabetes and impaired glucose tolerance are valid, this will have a
      major and adverse impact on the number of stroke patients globally.

PMID- 16276080
TI  - Acute stroke and diabetes.
AB  - Diabetes and hyperglycaemia are each over-represented amongst patients with acute
      stroke. Hyperglycaemia is associated with poor stroke outcome. Symptomatic
      intracranial haemorrhagic transformation is commoner in diabetes and
      hyperglycaemia but the treatment effect of thrombolysis appears not to be
      influenced by blood sugar level. Evidence from general patients treated in
      intensive care units suggests that intensive control of hyperglycaemia may
      improve early outcome; this evidence cannot be directly extrapolated to patients
      with acute stroke since supportive randomized controlled trial evidence
      describing benefits and risks of insulin administration for hyperglycaemia in
      stroke is scant. Nevertheless, at present the European guidelines suggest that
      glucose control may be advisable and place a threshold of 10 mmol/l for definite
      intervention; American guidelines are weaker. Glucose-potassium-insulin infusion
      or adjusted insulin infusions each have their proponents: both are effective but
      both carry a small risk of hypoglycaemia. Use of a suitable locally approved
      regimen seems advisable.

PMID- 16276081
TI  - Secondary prevention of stroke with antiplatelet agents in patients with diabetes
      mellitus.
AB  - The prevalence of diabetes mellitus (DM) varies from 1.2 to 13.3% in the general
      population. The most frequent is type 2 (non-insulin-dependent) DM, which
      constitutes 90-95% of all cases. DM increases the risk of cardiac disease,
      stroke, retinopathy, nephropathy, neuropathy and gangrene, and the disease is
      associated with an increased prevalence of other cardiovascular risk factors such
      as hypertension, hypercholesterolaemia, asymptomatic carotid artery disease, and
      obesity. The risk of stroke may be directly and indirectly increased by the
      presence of DM. Epidemiological data show that DM independently amplifies the
      risk of ischaemic stroke from 1.8- up to 6-fold, so that prevention of
      cardiovascular risk in diabetics is of utmost importance. The main goal is to
      control glycaemia, although it has never been shown to be beneficial in stroke
      patients. Other preventive strategies include antiplatelet treatment. The open
      label Primary Prevention Project trial tested the efficacy of low-dose
      acetylsalicylic acid (ASA) in prevention of ischaemic events in high-risk
      patients, but failed to demonstrate a significant benefit of ASA in diabetic
      patients. However, in the CAPRIE trial, the benefit of clopidogrel was amplified
      in patients with DM versus those without DM in preventing ischaemic events. This
      difference was even more striking when comparing patients treated with insulin
      versus non-diabetics. Another trial -- MATCH -- tested the benefit of adding ASA
      to clopidogrel versus clopidogrel alone in the prevention of ischaemic events in
      high-risk cerebrovascular patients, two-thirds of whom had DM. Further research
      is needed to clarify the effects of different antiplatelet regimens in stroke
      prevention in diabetic patients, who should be considered as high vascular-risk
      patients.

PMID- 16276082
TI  - Prevention of stroke in patients with diabetes mellitus and the metabolic
      syndrome.
AB  - The basic principles of stroke prevention are the same in patients with diabetes
      and/or the metabolic syndrome as in those without. Blood-pressure lowering is
      highly effective in both primary and secondary prevention of stroke in diabetics,
      and there is no evidence to suggest that the benefits of lipid-lowering therapy
      are any less. Antiplatelet agents are effective in secondary prevention and may
      be indicated in asymptomatic diabetic patients, who have a substantially
      increased risk of acute vascular events. Uncertainty over optimal management of
      patients with diabetes, and possibly of those with metabolic syndrome, relates
      more to the thresholds for initiation of treatment. The decision to initiate
      treatment should depend on the balance between the absolute risk of potentially
      preventable events and the risks of any complications of treatment. The absolute
      risks of ischaemic stroke and acute coronary events are significantly increased
      in diabetics in population-based cohort studies and the recommended thresholds
      for instigating blood pressure lowering and lipid lowering are therefore lower
      than in the general population. Optimization of strategies to prevent vascular
      complications must be a priority, given the rapid rises in the incidence and
      prevalence of type 2 diabetes and the metabolic syndrome in most populations
      across the globe.

PMID- 16276083
TI  - Inconsistencies between human genetic cytolocations and those derived using
      genomic sequence.
AB  - One result of the publishing of the human genome sequence is the ability to
      define objects through their position on the consensus sequence. While this has
      simplified the process of creating order maps for genes on a chromosome, it has
      created discrepancies between the published cytolocations of human genes, as
      presented through genetic references, and those locations derived computationally
      from the genomic sequence. For the 6,830 records with HUGO gene symbols shared
      between the online version of Mendelian Inheritance in Man and Ensembl, 18% of
      the records have a discrepancy of at least one cytogenetic band between the
      datasets. Discordance between data sets at this frequency would have a
      significant impact on the utility of datasets created by the amalgamation of
      numerous biological databases.

PMID- 16276084
TI  - 7E olfactory receptor gene clusters and evolutionary chromosome rearrangements.
AB  - Olfactory receptor (OR) genes of the 7E subfamily have been duplicated to
      multiple regions throughout the human genome. Segmental duplications containing
      7E OR genes have been associated with both pathological and evolutionary
      chromosome rearrangements. Many of these breakpoint regions coincide with breaks
      of chromosomal synteny in the mouse, rat and/or chicken genomes. Collectively,
      these data suggest that 7E OR-containing regions represent hot spots of genomic
      instability.

PMID- 16276085
TI  - Histone H3 lysine 4 dimethylation is enriched on the inactive sex chromosomes in
      male meiosis but absent on the inactive X in female somatic cells.
AB  - Inactivation of the X chromosome occurs in female somatic cells and in male
      meiosis. In both cases, the inactive X chromosome undergoes changes in histone
      modifications including deacetylation of core histone proteins and enrichment
      with histone H3 lysine 9 (H3-K9) dimethylation. In this study we show that while
      the inactive X in female somatic cells is largely devoid of H3-K4 dimethylation,
      the inactive X in male meiosis is enriched with this modification. However, the
      inactive X chromosome in female somatic cells and the inactive X and Y in male
      meiosis are devoid of H3-K4 trimethylation. Further, trimethylation of H3-K4 is
      present at discrete regions along most of the autosomes, while H3-K4
      dimethylation shows a more homogenous staining. Also, the Y chromosome is largely
      devoid of H3-K4 di- and trimethylation in somatic cells of both humans and mice,
      however, the Y chromosome is enriched with H3-K4 di- but not trimethylation
      throughout spermatogenesis. Our results provide insights into the differences
      between female somatic cells and male germ cells in inactivating the X
      chromosome, and suggest that trimethylation, and not dimethylation, of H3-K4 is a
      more robust indicator of the active regions of the genome.

PMID- 16276086
TI  - C21orf5, a human candidate gene for brain abnormalities and mental retardation in
      Down syndrome.
AB  - Mental retardation represents the more invalidating pathological aspect of
      trisomy 21 and has a hard impact on public health. The dosage imbalance of
      chromosome 21 genes could be the cause of neurological alterations and mental
      retardation seen in Down syndrome. We studied C21orf5 that we have demonstrated
      to be overexpressed in Down syndrome tissues, as a candidate gene for trisomy 21.
      A new optical technology (Rachidi et al., 2000) was used to compare signal
      intensity and cell density in presumptive embryonic brain compartments, at their
      boundaries and in higher specialized brain centres during fetal lifespan. We
      showed a developmentally regulated transcriptional activity of C21orf5 and a
      regional and cellular specific distribution of gene transcripts during human
      embryonic and fetal development. A wide but differential expression was detected
      in the nervous system during embryogenesis with a relatively lower level in the
      forebrain than in the midbrain and hindbrain and the highest transcription
      intensity in the future cerebellum. This developmentally regulated expression is
      maintained during post-embryogenesis and evolves selectively in fetal cerebral,
      hippocampal and cerebellar areas. Differential and cellular specificity were
      detected in hippocampus with higher C21orf5 mRNA level in the pyramidal cells
      compared to granular cells of the dentate gyrus. The expression pattern detected
      in cortical and cerebellar structures correlates well to the altered cortical
      lamination and to the lower size of the cerebellum observed in Down syndrome
      patients. In addition, the patterned differential expression detected in the
      medial temporal-lobe system, including hippocampal formation and perirhinal
      cortex, working as control centres of the memory circuits and involved in
      cognitive processes and memory storage, also corresponds to abnormal brain
      regions seen in Down syndrome patients. The C21orf5 selective expression in the
      key brain structures for learning and memory suggests that C21orf5 overexpression
      could participate in mental retardation pathogenesis in Down syndrome patients.

PMID- 16276087
TI  - Small supernumerary marker chromosomes--progress towards a genotype-phenotype
      correlation.
AB  - Small supernumerary marker chromosomes (sSMC) are still a major problem in
      clinical cytogenetics as they are too small to be characterized for their
      chromosomal origin by traditional banding techniques, but require molecular
      cytogenetic techniques for their identification. Apart from the correlation of
      about one third of the sSMC cases with a specific clinical picture, i.e. the
      i(18p), der(22), i(12p) (Pallister Killian syndrome) and inv dup(22) (cat-eye)
      syndromes, most of the remaining sSMC have not yet been correlated with clinical
      syndromes. Recently, we reviewed the available >1600 sSMC cases (Liehr T, sSMC
      homepage: http://mti-n.mti.uni-jena.de/~huwww/MOL_ZYTO/sSMC.htm). A total of 387
      cases (including the 45 new cases reported here) have been molecularly
      cytogenetically characterized with regard to their chromosomal origin, the
      presence of euchromatin, heterochromatin and satellite material. Based on
      analysis of these cases we present the first draft of a basic genotype-phenotype
      correlation for sSMC for all human chromosomes apart from the chromosomes Y, 10,
      11 and 13.

PMID- 16276088
TI  - Increased complexity of radiation-induced chromosome aberrations consistent with
      a mechanism of sequential formation.
AB  - Complex chromosome aberrations (any exchange involving three or more breaks in
      two or more chromosomes) are effectively induced in peripheral blood lymphocytes
      (PBL) after exposure to low doses (mostly single particles) of densely ionising
      high-linear energy transfer (LET) alpha-particle radiation. The complexity, when
      observed by multiplex fluorescence in situ hybridisation (m-FISH), shows that
      commonly four but up to eight different chromosomes can be involved in each
      rearrangement. Given the territorial organisation of chromosomes in interphase
      and that only a very small fraction of the nucleus is irradiated by each alpha
      particle traversal, the aim of this study is to address how aberrations of such
      complexity can be formed. To do this, we applied theoretical "cycle" analyses
      using m-FISH paint detail of PBL in their first cell division after exposure to
      high-LET alpha-particles. In brief, "cycle" analysis deconstructs the aberration
      "observed" by m-FISH to make predictions as to how it could have been formed in
      interphase. We propose from this that individual high-LET alpha-particle-induced
      complex aberrations may be formed by the misrepair of damaged chromatin in single
      physical "sites" within the nucleus, where each "site" is consistent with an
      "area" corresponding to the interface of two to three different chromosome
      territories. Limited migration of damaged chromatin is "allowed" within this
      "area". Complex aberrations of increased size, reflecting the path of alpha
      particle nuclear intersection, are formed through the sequential linking of these
      individual sites by the involvement of common chromosomes.

PMID- 16276090
TI  - In silico comparison of gene expression levels in ten human tumor types reveals
      candidate genes associated with carcinogenesis.
AB  - Most human cancers are characterized by genomic instability. Changes associated
      with such may result in altered expression of numerous genes. The sequence
      information available in the public databases can be used to identify transcripts
      differentially expressed in cancers. Determining cancer-related genes that are
      commonly deregulated in different tumor types may facilitate identification of
      targets for cancer diagnoses and therapeutic treatments. Using a data-mining tool
      named Digital Differential Display (DDD) from the UniGene database at the NCBI
      web site, gene expression levels of ten different tumor types and their
      counterpart normal tissues were analyzed. Unigenes which showed transcriptional
      regulation in more than five tumor types with > or =2-fold differences from
      normal tissues were identified. The expression data of selected Unigenes were
      subjected to clustering analysis. 127 commonly up-regulated genes and 92 commonly
      down-regulated genes were identified. Clustering analysis using these genes
      showed that most tumor types can be clustered into a separate branch from most
      normal tissues. Nineteen genes that have been shown to be involved in
      carcinogenesis by experimental evidence were also identified. Present
      computational analyses revealed 219 candidate cancer-related genes that are
      commonly deregulated in ten human tumor types which may contribute to the
      progress of carcinogenesis.

PMID- 16276089
TI  - Molecular characterisation of the t(1;15)(p22;q22) translocation in the prostate
      cancer cell line LNCaP.
AB  - Although chromosome translocations are well-documented recurrent events in
      hematological malignancies and soft tissue sarcomas, their significance in
      carcinomas is less clear. We report here the molecular characterization of the
      reciprocal translocation t(1;15)(p22;q22) in the prostate carcinoma cell line,
      LNCaP. The chromosome 1 breakpoint was localized to a single BAC clone, RP11
      290M5, by sequential FISH analysis of clones selected from the NCBI chromosome 1
      map. This was further refined to a 580-bp region by Southern blot analysis. A
      2.85-kb fragment spanning the der(1) breakpoint was amplified by long-range
      inverse PCR. The breakpoint on chromosome 1 was shown to lie between the CYR61
      and the DDAH1 genes with the der(1) junctional sequence linking the CYR61 gene to
      the TSPAN3 (TM4SF8) gene on chromosome 15. Confirmatory PCR and FISH mapping of
      the der(15) showed loss of chromosome material proximal to the breakpoint on
      chromosome 15, containing the PSTPIP1 and RCN2 genes. On the available evidence
      we conclude that this translocation does not result in an in-frame gene fusion.
      Comparative expressed sequence hybridization (CESH) and comparative genomic
      hybridization (CGH) analysis, showed relative down-regulation of gene expression
      surrounding the breakpoint, but no gross change in genomic copy number. Real-time
      quantitative RT-PCR for genes around the breakpoint supported the CESH data.
      Therefore, here we may have revealed a gene down-regulation mechanism associated
      with a chromosome translocation, either through small deletion at the breakpoint
      or through another means of chromosome domain related gene regulation.

PMID- 16276091
TI  - Truncation and fusion of HMGA2 in lipomas with rearrangements of 5q32-->q33 and
      12q14-->q15.
AB  - Chromosome segment 12q13-->q15 recombines with many different chromosome bands in
      lipomas and at least ten recurrent translocations have been identified. The HMGA2
      gene is often rearranged, but little is known about the molecular consequences at
      other breakpoints. Fusion genes between HMGA2 (12q14-->q15) and LPP (3q27-->q28),
      LHFP (13q12) and CMKOR1 (2q37) have been reported. In the present study, eight
      lipomas with rearrangements involving chromosome bands 12q14-->q15 and 5q32-->q33
      were analyzed. In chromosome 5, five of the cases had a breakpoint in the 5' part
      of EBF in 5q33, while three cases had breakpoints located about 200 kb 3' of EBF.
      In chromosome 12, the breakpoints clustered to the region of HMGA2. Four cases
      had breaks within the gene and four had breaks 5' to HMGA2 where the gene
      BC058822 is located. Two versions of an HMGA2/EBF fusion transcript were detected
      in one case; one transcript was in frame and the other out of frame. Identical
      EBF/BC058822 fusion transcripts, seen in two cases, one of which also had the
      HMGA2/EBF transcript, were out of frame and resulted in truncation of EBF. Since
      EBF and HMGA2 have different orientations, the findings must be explained by
      complex aberrations including multiple breaks. The combined data indicate that
      the pathogenetically significant event is fusion, truncation or transcriptional
      activation of HMGA2, but it can not be excluded that EBF, which has been
      implicated in adipogenesis, contributes to the tumor development.

PMID- 16276092
TI  - A molecular cytogenetic study of chromosome evolution in chimpanzee.
AB  - We applied multitude multicolor banding (mMCB) in combination with a novel FISH
      DNA probe set including subcentromeric, subtelomeric and whole chromosome
      painting probes (subCTM) to characterize a Pan paniscus (PPA) cell line. These
      powerful techniques allowed us to refine the breakpoints of a pericentric
      inversion on chimpanzee chromosome 4, and discovered a novel cryptic pericentric
      inversion in chimpanzee chromosome 11. mMCB provided a starting point for mapping
      and high resolution analysis of breakpoints on PPA chromosome 4, which are within
      a long terminal repeat (LTR) and surrounded by segmental duplications, as well as
      the integration/expansion sites of the interstitial heterochromatin on chimpanzee
      chromosomes 6 and 14. Moreover, we found evidence at hand for different types of
      heterochromatin in the chimpanzee genome. Finally, shedding new light on the
      human/chimpanzee speciation, karyotypes of three members of the genus Pan were
      studied by mMCB and no cytogenetic differences were found although the
      phylogenetic distance between these subspecies is suggested to be 2.5 million
      years.

PMID- 16276093
TI  - Trisomy of chromosome 18 in the baboon (Papio hamadryas anubis).
AB  - Trisomy 18 is usually a lethal chromosomal abnormality and is the second most
      common autosomal trisomy in humans, with an incidence of 1:8000 live births. It
      is commonly associated with abnormalities of the lower and upper extremities,
      having the frequency of 95% and 65%, respectively. A newborn female olive baboon
      (Papio hamadryas anubis) was diagnosed with intrauterine growth retardation and
      severe arthrogryposis-like congenital joint deformities. Cytogenetic analysis
      including G-banding and fluorescence in situ hybridization (FISH) revealed that
      the congenital abnormalities were associated with chromosomal mosaicism for
      trisomy 18. Genetic analysis with microsatellites from chromosome 18 confirmed
      the maternal origin of the extra chromosome 18. This is the first report of
      trisomy 18 in the baboon, which may be a promising animal model of human disease.

PMID- 16276094
TI  - Genomic structure and an alternative transcript of bovine mitochondrial glycerol
      3-phosphate acyltransferase gene (GPAM).
AB  - GPAM maps in BTA26q22, where several QTLs affecting milk production, milk fat and
      protein content have been mapped. On the basis of the QTL location, the GPAM gene
      could be considered a good candidate gene for the mentioned traits. Glycerol-3
      phosphate acyltransferase mitochondrial (GPAM) is the enzyme that catalyses the
      initial and committed step of glycerolipid synthesis and, therefore, it is a
      potential site for triacylglycerol synthesis regulation. In this study, the
      structure of the cDNA and the genomic DNA of the bovine GPAM gene were determined
      and the expression of its mRNA was studied. The cDNA of the gene was cloned by RT
      PCR, 5' and 3' rapid amplification of cDNA ends. The GPAM mRNA sequence contains
      a 2,475-bp coding region and a 3,689-bp 3' UTR. Its ORF encoded for an 825-amino
      acid protein and has an 89% homology with the coding regions of previously
      characterized mouse and human GPAM genes. The predicted amino acid sequence had
      an 89 and 93% similarity with mouse and human GPAM proteins, respectively. Using
      a 5' RACE strategy, two different 5' UTRs were cloned. Northern blot analysis
      confirmed the presence of two different transcripts. Adipose tissues and lung had
      the highest levels of GPAM mRNA expression, whereas it was barely detectable in
      liver. This expression pattern differs with those of non-ruminant animals where
      liver is one of the tissues with higher GPAM mRNA expression level.

PMID- 16276095
TI  - Sequencing, chromosomal mapping, and functional characterization of bovine FLICE
      like inhibitory protein (FLIP).
AB  - FLICE-like inhibitory protein (FLIP) has been shown in both humans and mice to
      inhibit apoptosis and NF-kappaB activation induced by pro-inflammatory mediators.
      The activation of NF-kappaB and the induction of apoptosis are critical events in
      the pathogenesis of a variety of disease states in cattle, including mastitis.
      Since FLIP is known to moderate these events in other species, we mapped the
      bovine FLIP gene, sequenced bovine FLIP cDNA, and characterized its expression in
      cultured primary bovine endothelial cells. Sequencing of bovine FLIP revealed
      approximately 83, 74, and 68% amino acid sequence identity to its porcine, human,
      and murine orthologs, respectively. Bovine FLIP was mapped to chromosome 2 by
      radiation hybrid mapping. Interestingly the region to which bovine FLIP maps
      contains a putative quantitative trait locus for functional herd life which is an
      indicator of a cow's ability to survive involuntary culling due primarily to
      mastitis and infertility. In addition to sequencing and mapping, the function of
      bovine FLIP was studied. Over-expression of bovine FLIP protected against
      bacterial lipopolysaccharide (LPS)- and TNF-alpha-induced apoptosis in bovine
      endothelial cells consistent with previous studies of human FLIP. In addition,
      elevated expression of bovine FLIP blocked LPS- and TNF-alpha-induced
      upregulation of NF-kappaB-dependent gene products as assayed by E-selectin
      expression. Only the full-length bovine FLIP protein could inhibit NF-kappaB
      activation induced by LPS, whereas the death effector domain region alone was
      able to inhibit TNF-alpha-induced NF-kappaB activation. Together, these data
      demonstrate the conservation of FLIP's ability to inhibit apoptosis and to
      downregulate NF-kappaB activation across species.

PMID- 16276096
TI  - Comparative mapping of bovine chromosome 27 with human chromosome 8 near a dairy
      form QTL in cattle.
AB  - In the absence of a complete and annotated bovine genome sequence, detailed human
      bovine comparative maps are one of the most effective tools for identification of
      positional candidate genes contributing to quantitative trait loci (QTL) in
      cattle. In the present study, eight genes from human chromosome 8 were selected
      for mapping in cattle to improve breakpoint resolution and confirm gene order on
      the comparative map near the 40 cM region of the BTA27 linkage map where a QTL
      affecting dairy form had previously been identified. The resulting map identified
      ADRB3 as a positional candidate gene for the QTL contributing to the dairy form
      trait based on its estimated position between 40 and 45 cM on the linkage map. It
      is also a functional candidate gene due to its role in fat metabolism, and
      polymorphisms in the ADRB3 gene associated with obesity and metabolic disease in
      humans, as well as, carcass fat in sheep. Further studies are underway to
      investigate the existence of polymorphisms in the bovine ADRB3 gene and their
      association with traits related to fat deposition in cattle.

PMID- 16276097
TI  - Comparative FISH mapping of mucin 1, transmembrane (MUC1) among cattle, river
      buffalo, sheep and goat chromosomes: comparison between bovine chromosome 3 and
      human chromosome 1.
AB  - Four bovine BAC clones (0494F01, 0069D07, 0060B06, and 0306A12) containing MUC1,
      as confirmed by mapping MUC1 on a RH3000 radiation hybrid panel, were hybridised
      on R-banded chromosomes of cattle (BTA), river buffalo (BBU), sheep (OAR) and
      goat (CHI). MUC1 was FISH-mapped on BTA3q13, BBU6q13, OAR1p13 and CHI3q13 and
      both chromosomes and chromosome bands were homoeologous confirming the high
      degree of chromosome homoeologies among bovids and adding more information on the
      pericentromeric regions of these species' chromosomes. Indeed, MUC1 was more
      precisely assigned to BTA3 and assigned for the first time to BBU6, OAR1p and
      CHI3. Moreover, detailed and improved cytogenetic maps of BTA3, CHI3, OAR1p and
      BBU6 are shown and compared with HSA1.

PMID- 16276098
TI  - Porcine PPARGC1A (peroxisome proliferative activated receptor gamma coactivator
      1A): coding sequence, genomic organization, polymorphisms and mapping.
AB  - We report here the characterisation of porcine PPARGC1A. Primers based on human
      PPARGC1A were used to isolate two porcine BAC clones. Porcine coding sequences of
      PPARGC1A were sequenced together with the splice site regions and the 5' and 3'
      regions. Using direct sequencing nine SNPs were found. Allele frequencies were
      determined in unrelated animals of five different pig breeds. In the MARC Meishan
      White Composite resource population, the polymorphism in exon 9 was significantly
      associated with leaf fat weight. PPARGC1A has been mapped by FISH to SSC8p21. A
      (CA)n microsatellite (SGU0001) has been localised near marker SWR1101 on
      chromosome 8 by RH mapping and at the same position as marker KS195 (32.5 cM) by
      linkage mapping. The AseI (nt857, Asn/Asn489) polymorphism in exon 8 was used to
      perform linkage analysis in the Hohenheim pedigrees and located the gene in the
      same genomic region. Transcription of the gene was detected in adipose, muscle,
      kidney, liver, brain, heart and adrenal gland tissues, which is in agreement with
      the function of PPARGC1A in adaptive thermogenesis.

PMID- 16276099
TI  - Assignment of 204 genes localized on HSA17 to a porcine RH (IMpRH) map to
      generate a dense comparative map between pig and human/mouse.
AB  - Bi- and uni-directional chromosome painting (ZOO-FISH) and gene mapping have
      revealed correspondences between human chromosome (HSA) 17 and porcine chromosome
      (SSC) 12 harboring economically important quantitative trait loci. In the present
      study, we have assigned 204 genes localized on HSA17 to SSC12 to generate a
      comprehensive comparative map between HSA17 and SSC12. Two hundred fifty-five
      primer pairs were designed using porcine sequences orthologous with human genes.
      Of the 255 primer pairs, 208 (81.6%) were used to assign the corresponding genes
      to porcine chromosomes using the INRA-Minnesota 7000-rad porcine x Chinese
      hamster whole genome radiation hybrid (IMpRH) panel. Two hundred three genes were
      integrated into the SSC12 IMpRH linkage maps; and one gene, PPARBP, was found to
      link to THRA1 located in SSC12 but not incorporated into the linkage maps. Three
      genes (GIT1, SLC25A11, and HT008) were suggested to link to SSC12 markers, and
      the remaining gene (RPL26) did not link to any genes/expressed sequence
      tags/markers registered, including those in the present study. A comparison of
      the gene orders among SSC12, HSA17, and mouse chromosome 11 indicates that intra
      chromosomal rearrangements occurred frequently in this ancestral mammalian
      chromosome during speciation.

PMID- 16276100
TI  - Assignment of 101 genes localized in HSA10 to a swine RH (IMpRH) map to generate
      a dense human-swine comparative map.
AB  - Economically important traits such as growth and backfat in pigs have been shown
      to be influenced by genes in swine chromosome (SSC) 10q12-->qter corresponding to
      human chromosome (HSA) 10p. However, since gene information in the swine
      chromosomal region was limited, we attempted to generate a dense comparative map
      between SSC10 and HSA10 by mapping the 115 genes of HSA10 to a swine RH map
      (IMpRH map). In the mapping ten genes were assigned to SSC10, 88 to SSC14, and
      one to SSC3. One gene was suggested to link to SSC3, and another to SSC9. The
      correspondences between HSA10 and SSC10 and between HSA10 and SSC14 were
      essentially consistent with the observations obtained from bi/uni-directional
      chromosome painting or other results. This study further indicated that a large
      number of intrachromosomal rearrangements occurred in the synteny-conserved
      regions following species separation.

PMID- 16276101
TI  - Further insights into the ancestral murine karyotype: the contribution of the
      Otomys-Mus comparison using chromosome painting.
AB  - The African vlei rat, Otomys irroratus, comprises several distinct chromosomal
      races that may be grouped into two major cytogenetic clades. Recognition of these
      clades is underpinned by a complex chromosomal rearrangement involving three
      different autosomes in the unfused state. We have used unidirectional
      fluorescence in situ hybridization (FISH) of mouse chromosome-specific painting
      probes to molecularly define the components of this rearrangement as well as to
      establish the chromosomal homologies between the mouse and the vlei rat genomes.
      This has allowed for the detection of 41 autosomal segments of conserved synteny.
      Nine mouse chromosomes were conserved in toto (MMU3, 4, 6, 7, 11, 12, 14, 18, 19)
      with a further seven (MMU2, 5, 8, 9, 10, 13, 16) showing homology to two discrete
      regions in the vlei rat genome. Two mouse autosomes (MMU15, 17) correspond to
      three regions in O. irroratus with MMU1 being the most fragmented showing five
      sites of hybridization in this species. By mapping these data to published
      sequence-based phylogenies we are able to confirm most of the published putative
      ancestral murine chromosomal states. Our data further indicate that MMU15a+
      MMU13b+MMU10b+MMU17b was present in the murine ancestral karyotype suggesting an
      ancestral 2n = 52 rather than the 2n = 54 previously postulated.

PMID- 16276102
TI  - Unusually extensive karyotype reorganization in four congeneric Gerbillus species
      (Muridae: Gerbillinae).
AB  - Comparative analysis of the G- and C-banding patterns in four morphologically
      poorly differentiated Gerbillus species (G. pyramidum, G. perpallidus, G.
      tarabuli and G. occiduus) was carried out. These gerbils have similar karyotype
      morphology with 2n and NF equal to 38/76, 40/76, 40/78 and 40/80, respectively.
      Our study revealed that possibly 70 Robertsonian (Rb) fusions, two pericentric
      inversions, one tandem translocation and at least 13 non-identified
      rearrangements have occurred during the karyotypic evolution of these species.
      The number of chromosomal changes by which any of these species differ from each
      other ranges from 33 to 49. One Rb fusion was common to two of the species, with
      only a single autosome-gonosome translocation shared by all four, suggesting a
      monophyletic origin of these karyotypically highly divergent species. Based on
      the chromosomal data obtained here, the systematic and geographic implications
      for these North African species are also discussed.

PMID- 16276103
TI  - Chromosomal assignment of LASP1 and LASP2 genes and organization of the LASP2
      gene in chicken.
AB  - Lasp-1 and lasp-2 are actin-binding proteins that contain a LIM domain, two
      nebulin repeats and an SH3 domain with significant identity. We determined the
      chromosomal locations of the LASP1 and LASP2 genes in chicken by fluorescence in
      situ hybridization. The LASP1 gene was localized to a pair of microchromosomes
      and the LASP2 gene was localized to chromosome 2p3.1, indicating that the
      chromosomal locations of the LASP1 and LASP2 genes are highly conserved between
      chicken and human. The comparison of genomic and cDNA sequences of chicken lasp-2
      and nebulette, a nebulin-related protein in muscle, suggested that both the
      corresponding mRNAs shared exons in the same manner as their human homologues.
      When compared with the domain structure of nebulette, another nebulin repeat was
      predicted for lasp-2, and all the nebulin repeats of lasp-2 were better conserved
      than those in nebulette. We also found the exon boundaries in nebulin repeats of
      lasp-2 were similar to those of other nebulin-related proteins.

PMID- 16276104
TI  - cDNA cloning, genomic structure, chromosomal mapping and expression analysis of
      ADIPOQ (adiponectin) in chicken.
AB  - We report sequence, tissue expression and map position data for the adiponectin
      gene (ADIPOQ) in chicken. This gene is involved in adipocyte differentiation in
      mammals and may play similar roles in chicken. The complete coding sequence of
      chicken ADIPOQ encodes a 244 amino acid protein. The coding region of the chicken
      ADIPOQ is organized in two exons and spans an approximately 2.1 kb genomic
      region. Domain/motif structures of the adiponectin protein among chicken and
      mammalian homologs are highly conserved. Reverse transcription-PCR revealed
      chicken ADIPOQ mRNA displayed high expression levels in fat tissue, heart,
      stomach and skin and weak expression in muscle. Analysis of a radiation hybrid
      panel indicated that ADIPOQ showed the most significant linkage to FOXL2 (LOD =
      12.63, 12 cR) and ATSV (LOD = 7.53, 3 cR) both of which are located on chicken
      chromosome 9. Information provided in this study will be useful in further
      studies to determine the role the adiponectin gene plays in the regulation of
      glucose and lipid metabolism and body weight in chicken.

PMID- 16276105
TI  - Identification of the sex-determining locus of Atlantic salmon (Salmo salar) on
      chromosome 2.
AB  - We have integrated data from linkage mapping, physical mapping and karyotyping to
      gain a better understanding of the sex-determining locus, SEX, in Atlantic salmon
      (Salmo salar). SEX has been mapped to Atlantic salmon linkage group 1 (ASL1) and
      is associated with several microsatellite markers. We have used probes designed
      from the flanking regions of these sex-linked microsatellite markers to screen a
      bacterial artificial chromosome (BAC) library, representing an 11.7x coverage of
      the Atlantic salmon genome, which has been HindIII fingerprinted and assembled
      into contigs. BACs containing sex-linked microsatellites and their related
      contigs have been identified and representative BACs have been placed on the
      Atlantic salmon chromosomes by fluorescent in situ hybridization (FISH). This
      identified chromosome 2, a large metacentric, as the sex chromosome. By
      positioning several BACs on this chromosome by FISH, it was possible to orient
      ASL1 with respect to chromosome 2. The region containing SEX appears to lie on
      the long arm between marker Ssa202DU and a region of heterochromatin identified
      by DAPI staining. BAC end-sequencing of clones within sex-linked contigs revealed
      five hitherto unmapped genes along the sex chromosome. We are using an in silico
      approach coupled with physical probing of the BAC library to extend the BAC
      contigs to provide a physical map of ASL1, with a view to sequencing chromosome 2
      and, in the process, identifying the sex-determining gene.

PMID- 16276106
TI  - Molecular cytogenetic characterization and chromosomal distribution of the
      satellite DNA in the genome of Oxya hyla intricata (Orthoptera: Catantopidae).
AB  - The genomic DNA of the grasshopper (Oxya hyla intricata) was subjected to
      electrophoresis after digestion with HaeIII, and the result showed two bands of
      highly repetitive DNA, approximately 200 and 400 bp in length. The 200-bp HaeIII
      digested fragment was cloned and characterized by sequencing and fluorescence in
      situ hybridization (FISH). The results showed the presence of two distinct
      satellite DNA (stDNA) families: one consisting of a 169-bp repeated element
      having an A+T content of 60.9% and the other consisting of a 204-bp repeated
      element having an A+T content of 53.9%. No significant homology between the two
      stDNA families was observed. FISH showed that the chromosomal locations of these
      families are different from each other. The 169-bp element was located in the C
      band-positive regions of the short arms of most of the chromosomes, whereas the
      204-bp element was located in the centromeric regions of three chromosome pairs.
      These results imply that the origins of these two DNA families are different. The
      results of zoo-blot hybridization to the genomic DNA from four Oxya species, O.
      hyla intricata, O. japonica japonica, O. chinensis formosana, and O. yezoensis,
      suggest that the two stDNA families found in the present study are species
      specific for O. hyla intricata.

PMID- 16276107
TI  - Molecular investigation of a dicentric 13;17 chromosome found in a 21-week
      gestation fetus with multiple congenital abnormalities.
AB  - We report a 21-week gestation fetus terminated because of multiple congenital
      abnormalities seen on ultrasound scan, including ventriculomegaly, possible
      clefting of the hard palate, cervical hemivertebrae, micrognathia, abnormal
      heart, horseshoe kidney and a 2-vessel umbilical cord. On cytogenetic
      examination, the fetus was found to have a male karyotype with 45 chromosomes
      with a dicentric chromosome, which appeared to consist of the long arms of
      chromosomes 13 and 17. Molecular genetic investigations and fluorescence in situ
      hybridization (FISH) unexpectedly showed that the derivative chromosome contained
      two interstitial blocks of chromosome 17 short arm sequences, totalling
      approximately 7 Mb, between the two centromeres. This effectively made the fetus
      monosomic for approximately 15 Mb of 17p without the concurrent trisomy for
      another chromosome normally seen following malsegregation of reciprocal
      translocations. It also illustrates the complexity involved in the formation of
      some structurally abnormal chromosomes, which can only be resolved by detailed
      molecular investigations.

PMID- 16276109
TI  - Complex mosaicism in sex reversed SRY+ male twins.
AB  - Sex reversal is characterized by discordance between genetic and phenotypic sex.
      Most XX males result from an unequal interchange between X and Y chromosomes
      during paternal meiosis, therefore transferring SRY to the X chromosome, which
      explains the male development in the presence of an otherwise normal female
      karyotype. We present here the case of sex reversed SRY+ male twins with several
      cell lines. They consulted for infertility. The presence of SRY on an X
      chromosome was demonstrated by FISH. Their respective karyotypes were:
      46,X,der(X)t(X;Y)(p22.3;p11.2)[249]/45,X
      [12]/45,der(X)t(X;Y)(p22.3;p11.2)[11]/47,XX,der(X)t(X;Y)
      (p22.3;p11.2)[1]/47,X,der(X)t(X;Y)(p22.3;p11.2)x2[1]/50,
      XX,der(X)t(X;Y)(p22.3;p11.2)x4[1]/46,XX[1] for the first twin (SH-1) and
      46,X,der(X)t(X;Y)(p22.3;p11.2)[108]/45,X
      [3]/47,XX,der(X)t(X;Y)(p22.3;p11.2)[2]/45,der(X)t(X;Y)
      (p22.3;p11.2)[1]/47,X,der(X)t(X;Y)(p22.3;p11.2)x2[1] for the second twin (SH-2).
      There are three different types of XX males: 1) with normal genitalia, 2) with
      genital ambiguity, and 3) XX true hermaphrodites. The phenotype of the twins
      presented in this report is consistent with what is generally seen in XX SRY+
      males: they have normal genitalia.

PMID- 16276108
TI  - Disruption of DMD and deletion of ACSL4 causing developmental delay, hypotonia,
      and multiple congenital anomalies.
AB  - We have studied a male patient with significant developmental delay, growth
      failure, hypotonia, girdle weakness, microcephaly, and multiple congenital
      anomalies including atrial (ASD) and ventricular (VSD) septal defects. Detailed
      cytogenetic and molecular analyses revealed three de novo X chromosome
      aberrations and a karyotype 46,Y,der(X)inv(X) (p11.4q11.2)inv(X)(q11.2q21.32
      approximately q22.2)del(X)(q22.3q22.3) was determined. The three X chromosome
      aberrations in the patient include: a pericentric inversion (inv 1) that
      disrupted the Duchenne muscular dystrophy (DMD) gene, dystrophin, at Xp11.4; an
      Xq11.2q21.32 approximately q22.2 paracentric inversion (inv 2) putatively
      affecting no genes; and an interstitial deletion at Xq22.3 that results in
      functional nullisomy of several known genes, including a gene previously
      associated with X-linked nonsyndromic mental retardation, acyl-CoA synthetase
      long chain family member 4 (ACSL4). These findings suggest that the disruption of
      DMD and the absence of ACSL4 in the patient are responsible for neuromuscular
      disease and cognitive impairment.

PMID- 16276110
TI  - Conversion of mild cognitive impairment to dementia: predictive role of mild
      cognitive impairment subtypes and vascular risk factors.
AB  - Mild cognitive impairment (MCI) is regarded as a precursor to dementia, but not
      all patients with MCI develop dementia. We followed up 165 elderly outpatients
      with MCI for a mean of 3 years. The aims were (1) to investigate the risk of
      conversion to dementia for different MCI subtypes diagnosed according to
      standardized criteria (amnestic; impairment of memory plus other cognitive
      domains; nonamnestic); (2) to assess whether the risk of conversion was affected
      by several established and emerging vascular risk factors. Forty-eight subjects
      (29%) converted to dementia, and the risk of conversion was doubled for amnestic
      MCI with respect to the other subtypes. Independently of MCI subtype, risk of
      conversion was associated with atrial fibrillation and low serum folate levels.
      Our results show that current diagnostic criteria for MCI define heterogeneous
      populations, but some potentially treatable vascular risk factors may be of help
      in predicting conversion to dementia.

PMID- 16276111
TI  - Early-onset dementia: frequency and causes compared to late-onset dementia.
AB  - BACKGROUND: Research on the epidemiology of dementia has focused on the elderly.
      Few investigations have studied differences in etiologic frequencies between
      early-onset dementia (EOD), with onset at an age of less than 65 years old, and
      the more common late-onset disorder. OBJECTIVES: To determine relative
      frequencies and characteristics of EOD versus late-onset dementia (LOD; age of
      onset > or =65 years) diagnosed in a large memory disorders program over a 4-year
      period. METHODS: We reviewed medical records, including an extensive
      neurobehavioral and neurological evaluation, of all patients seen at a large
      Veteran's Affairs Medical Center Memory Disorders clinic between 2001 and 2004
      and assessed demographic variables, final diagnoses, presence of dementia, and
      differential diagnosis of dementing illnesses. RESULTS: Among 1,683 patients
      presenting for evaluation of an acquired decline in memory or cognition, 948
      (56%) met established clinical criteria for a dementing illness. About 30% (n =
      278) of these had an age of onset of <65 years, compared to 670 with LOD.
      Patients were predominantly male (98%). Compared to the late-onset group, the EOD
      patients were less severely impaired on presentation, but they did not differ in
      gender distribution or educational background. The EOD group had significantly
      more dementia attributed to traumatic brain injury, alcohol, human
      immunodeficiency virus (HIV), and frontotemporal lobar degeneration compared to
      the LOD patients. In contrast, the LOD group had significantly more Alzheimer's
      disease compared to the EOD group. CONCLUSIONS: This study, conducted at a
      Veterans Affairs Hospital, is the largest series to date on EOD, and found a
      previously unexpectedly large number of patients below the age of 65 with
      cognitive deficits and impaired functioning consequent to head trauma, alcohol
      abuse, and HIV. These findings highlight the differential distribution and
      importance of preventable causes of dementia in the young.

PMID- 16276112
TI  - Identification of hevamine and hev B 1 as major latex allergens in Taiwan.
AB  - BACKGROUND: Proteins from latex gloves have been documented to trigger
      occupational latex allergy among health care workers. Allergen characterization
      of latex glove extract has never been studied in Taiwan. This study aimed to
      identify allergenic proteins from latex gloves. METHODS: Crude extracts of latex
      gloves were prepared with phosphate-buffered saline and 20 medical workers with a
      history of latex allergy were enrolled in this study. The specific IgE antibody
      was determined by the Pharmacia CAP system and in-house enzyme-linked immunoassay
      and immunoblotting. The target proteins were excised from two-dimensional PAGE
      and analyzed by electrospray ionization tandem mass spectrometry. RESULTS:
      Immunoblotting of glove extracts revealed three IgE-binding proteins at a
      molecular mass of 45, 30 and 14 kDa. Peptide mass fingerprinting revealed that
      the protein at 45 kDa, which was recognized by 10% (2/20) of atopic sera tested,
      was an allergenic lipolytic esterase from Hevea brasiliensis (Hev b 13). The 30-
      and 14-kDa proteins, which were recognized by 55% (11/20) and 85% (17/20) of
      patients' sera, were found to be hevamine and rubber elongation factor (Hev b 1),
      respectively. CONCLUSIONS: Our results indicated that hevamine and Hev b 1 are
      the major allergens from latex gloves in Taiwan, which differs from the reports
      in Western countries.

PMID- 16276113
TI  - Identification and possible disease mechanisms of an under-recognized fungus,
      Aureobasidium pullulans.
AB  - BACKGROUND: Investigations into the occurrence and health effects of yeast-like
      fungi in the outdoor air in the US have been limited. We sought to identify a
      respirable-sized fungus common in the Pasadena air, locate a major source for the
      emissions and investigate its relevance to allergic disease. METHODS: Yeast-like
      fungi sampled from the environment were isolated, microscopically examined and
      sequenced. Pasadena allergy patients were skin tested with commercially available
      fungal extracts. Patient serum was immunoanalyzed for specific IgE reactivity.
      Nearby vegetation was analyzed in a controlled emission chamber to find a major
      source for the aerosols. RESULTS: Hyaline unicellular conidia comprised up to 90%
      (41,250 m(-3) of air) of total fungal counts and generally peaked at night and
      during periods of rainfall and ensuing winds throughout the fall and winter.
      Flowers were determined to be a major source of the emissions. The cellular and
      colonial morphology of isolates were consistent with Aureobasidium species. The
      sequence of the D1/D2 region of the 26S ribosomal subunit of isolates from
      flowers showed identity to two strains of Aureobasidium pullulans (black yeast).
      Seventeen percent (16/94) of atopic individuals had positive skin testing with A.
      pullulans extract. Patient sera IgE identified several high molecular weight
      allergens in Aureobasidium extracts. CONCLUSIONS: Respirable-sized conidia of A.
      pullulans are emitted from flowers and form high concentrations in the air. They
      are associated with immediate reactivity on skin tests, bind to patient sera IgE,
      and might be relevant in allergic upper and lower airway diseases.

PMID- 16276114
TI  - Physiologically relevant measurements of nitric oxide in cardiovascular research
      using electrochemical microsensors.
AB  - Nitric oxide (NO) plays an important role in the regulation of blood flow.
      Pharmacological tools and a series of other techniques have been developed for
      studying the NO/L-arginine pathway, but it has proved difficult to make a
      quantitative link between effect and tissue NO concentration. NO microsensors
      have been applied with success for the measurement of NO in suspensions of
      mitochondria and cells, such as platelets and leukocytes, and in cell cultures,
      which together with other interventions or measurements are particularly useful
      for the examination of cell signalling related to the NO/L-arginine pathway. In
      isolated vascular segments, studies using the NO microsensor have defined the
      relationship between NO concentration and relaxation and revealed residual NO
      release in the presence of NO synthase inhibitors. Moreover, simultaneous
      measurements of NO concentration and vasorelaxation in isometric preparations
      have shown that agonist-induced relaxation is L-arginine dependent and NO release
      is reduced in hypertension. By placing NO microsensors in catheters, it is
      possible to measure NO in the living animal and man. This approach has been
      applied for the measurements of NO concentration in relation to increases in
      flow, erection, in conditions of hypoxia, and in endotoxemia. However, further
      methodological development of NO microsensors is necessary to avoid the influence
      of changes in temperature, pH and oxygen on the measurements.

PMID- 16276115
TI  - Age-related changes in hypothalamic-pituitary-adrenal axis activity of male
      C57BL/6J mice.
AB  - As there is little known about age-related changes in the hypothalamic-pituitary
      adrenal (HPA) axis of mice, we determined the daily patterns of corticosterone
      secretion every 2 h, together with adrenocorticotropic hormone (ACTH) release and
      central HPA axis markers in the morning and evening of 3-, 9- and 16-month-old
      male C57BL/6J mice. We observed that: (i) corticosterone secretion showed a
      distinct age-related circadian pattern. During the light period this was
      expressed by relative hypercorticism in 9-month-old mice and relative
      hypocorticism in 16-month-old mice. ACTH was elevated at 16 months of age; (ii)
      mineralocorticoid (MR) and glucocorticoid receptor (GR) mRNA expression in the
      hippocampus was significantly decreased in 9-month-old mice, whereas in 16-month
      old mice, expression was similar to young animals. Circadian variation was modest
      in all age groups; (iii) the parvocellular hypothalamic paraventricular nucleus
      (PVN) expressed very high vasopressin mRNA, which was subject to circadian
      variation in 3- and 9-month-old mice. Furthermore, significant levels of MR mRNA
      were expressed in the PVN. In conclusion, basal HPA axis activity and expression
      of its central regulatory markers are age-dependent in mice. This suggests that
      the capacity to adjust to environmental demands is either a function of age, or
      depends on different dynamics of the HPA axis.

PMID- 16276116
TI  - Insights into GABA receptor signalling in TM3 Leydig cells.
AB  - Gamma-aminobutyric acid (GABA) is an emerging signalling molecule in endocrine
      organs, since it is produced by endocrine cells and acts via GABA(A) receptors in
      a paracrine/autocrine fashion. Testicular Leydig cells are producers and targets
      for GABA. These cells express GABA(A) receptor subunits and in the murine Leydig
      cell line TM3 pharmacological activation leads to increased proliferation. The
      signalling pathway of GABA in these cells is not known in this study. We
      therefore attempted to elucidate details of GABA(A) signalling in TM3 and adult
      mouse Leydig cells using several experimental approaches. TM3 cells not only
      express GABA(A )receptor subunits, but also bind the GABA agonist [(3)H]muscimol
      with a binding affinity in the range reported for other endocrine cells (K(d) =
      2.740 +/- 0.721 nM). However, they exhibit a low B(max) value of 28.08 fmol/mg
      protein. Typical GABA(A) receptor-associated events, including Cl(-) currents,
      changes in resting membrane potential, intracellular Ca(2+) or cAMP, were not
      measurable with the methods employed in TM3 cells, or, as studied in part, in
      primary mouse Leydig cells. GABA or GABA(A) agonist isoguvacine treatment
      resulted in increased or decreased levels of several mRNAs, including
      transcription factors (c-fos, hsf-1, egr-1) and cell cycle-associated genes
      (Cdk2, cyclin D1). In an attempt to verify the cDNA array results and because egr
      1 was recently implied in Leydig cell development, we further studied this
      factor. RT-PCR and Western blotting confirmed a time-dependent regulation of egr
      1 in TM3. In the postnatal testis egr-1 was seen in cytoplasmic and nuclear
      locations of developing Leydig cells, which bear GABA(A) receptors and correspond
      well to TM3 cells. Thus, GABA acts via an atypical novel signalling pathway in
      TM3 cells. Further details of this pathway remain to be elucidated.

PMID- 16276117
TI  - Sex differences in hippocampal estradiol-induced N-methyl-D-aspartic acid binding
      and ultrastructural localization of estrogen receptor-alpha.
AB  - Estradiol increases dendritic spine density and synaptogenesis in the CA1 region
      of the female hippocampus. This effect is specific to females, as estradiol
      treated males fail to show increases in hippocampal spine density. Estradiol
      induced spinogenesis in the female is dependent upon upregulation of the N-methyl
      D-aspartic acid (NMDA) receptor as well as on non-nuclear estrogen receptors
      (ER), including those found in dendrites. Thus, in the male, the inability of
      estradiol to induce spinogenesis may be related to a failure of estradiol to
      increase hippocampal NMDA receptors as well as a paucity of dendritic ER. In the
      first experiment, we sought to investigate this possibility by assessing NMDA
      receptor binding, using [(3)H]-glutamate autoradiography, in estradiol-treated
      males and females. We found that while estradiol increases NMDA binding in
      gonadectomized females, estradiol fails to modulate NMDA binding in
      gonadectomized males. To further investigate sex differences in the hippocampus,
      we conducted a second separate, but related, ultrastructural study in which we
      quantified ERalpha-immunoreactivity (ERalpha-ir) in neuronal profiles in the CA1
      region of the hippocampus in intact males and females in diestrus and proestrus.
      Consistent with previous reports in the female, we found ERalpha-ir in several
      extranuclear sites including dendrites, spines, terminals and axons. Statistical
      analyses revealed that females in proestrus had a 114.3% increase in ERalpha
      labeled dendritic spines compared to females in diestrus and intact males. Taken
      together, these studies suggest that both the ability of estrogen to increase
      NMDA binding in the hippocampus and the presence of ERalpha in dendritic spines
      may contribute to the observed sex difference in estradiol-induced hippocampal
      spinogenesis.

PMID- 16276118
TI  - Solitary microcarcinoid of the rectal stump in ulcerative colitis.
AB  - A case of solitary microcarcinoid and chronic ulcerative colitis of the rectal
      stump is described. The association of intestinal carcinoid with ulcerative
      colitis has been reported previously in 26 patients. Pathogenic pathways are
      discussed according to the presence of multifocal carcinoid and/or gut endocrine
      cell hyperplasia.

PMID- 16276119
TI  - Association of E-cadherin gene 3'-UTR C/T polymorphism with primary open angle
      glaucoma.
AB  - PURPOSE: E-cadherin (E-CDH) is one of the most important cell surface
      glycoproteins involved in cell morphogenesis. In primary open angle glaucoma
      (POAG), the extracellular matrixes of trabecular meshwork and lamina cribrosa in
      the optic nerve head are out of balance. We suspected that E-CDH by way of
      metalloproteinases is closely related to POAG. We therefore investigated the
      relationship between CDH-1 gene 3' untranslated region (3'-UTR) polymorphism and
      POAG patients in order to support this hypothesis. PATIENTS AND METHODS: We
      enrolled 60 POAG patients and 103 healthy volunteers from the Department of
      Ophthalmology at the China Medical University Hospital, Taichung, Taiwan, ROC.
      None of the control subjects had a history of eye disease and all underwent the
      same examination as the POAG patients. PCR-based analysis of the restriction
      fragment length polymorphism was used to test the CDH-1 gene 3'-UTR polymorphism.
      All statistical analyses were performed by the chi(2) test. RESULT: There was a
      significant difference in the distribution of the CDH-1 gene 3'-UTR C/T
      polymorphism between POAG patients and the normal controls (p <0.000). The odds
      ratio of the 'C' allele was al so significantly different between both groups
      (odds ratio = 5.510, 95% confidence interval = 3.171-9.574). CONCLUSION: CDH-1 is
      closely related to metalloproteinase and plays an important but not well
      understood role in the onset and progression of POAG. The exact role of CDH-1 in
      POAG could be resolved by the posttranslated products of the gene and the protein
      protein interaction of the gene products in the future.

PMID- 16276121
TI  - Hemispheric difference in activation patterns of human auditory-associated
      cortex: an FMRI study.
AB  - The purpose of this study was to demonstrate interhemispheric differences in
      activation patterns of the auditory-associated cortex elicited by a series of
      sounds. Functional magnetic resonance imaging was performed while different
      sounds were presented binaurally to 10 healthy subjects with normal hearing.
      Characteristic activation patterns were elicited although variability was shown
      between subjects. The activation number was significantly higher on the right
      than on the left side for non-speech (but not for speech) stimulations. As
      stimulation increased in complexity (from a pure tone to white noise to ocean
      wave sounds to classical music), the activation pattern of the superior temporal
      lobe became more pronounced in both hemispheres while that of the auditory cortex
      tended to become more sustained and concentrated on the right rather than on the
      left side. No hemispheric differences in activation pattern were seen in response
      to speech.

PMID- 16276120
TI  - Investigation of a broad-spectrum PCR assay for human papillomaviruses in
      screening benign lesions of the upper aerodigestive tract.
AB  - BACKGROUND: A variety of different human papillomavirus (HPV) types can be found
      in benign and malignant lesions of the upper aerodigestive tract. Therefore a
      broad-spectrum assay is needed for screening reasons. METHODS: A PCR system with
      degenerate consensus primers originating from a very conserved region (e.g. L1)
      of the HPV genome was applied. The sensitivity level was improved by combining
      PCR and nested PCR. RESULTS: A total of 27 biopsies from laryngeal papillomas
      (9), exophytic (3) and inverted (6) papillomas of the nasal cavity or paranasal
      sinuses, papillomas of the uvula or soft palate (5), leukoplakias of the larynx
      (2), seborrheic keratosis (1) and granulation tumor of the tongue (1) were
      analyzed by the broad-spectrum PCR system. Sixteen cases showed a positive result
      in either PCR or nested PCR or both. CONCLUSIONS: It was shown that the applied
      broad-spectrum PCR system is a reliable tool in the detection of HPV DNA in
      benign lesions of the upper aerodigestive tract.

PMID- 16276122
TI  - Functional interaction of a beta-adrenergic agonist and cyclic GMP
      phosphodiesterase inhibitor in control and hypertrophic cardiomyocytes.
AB  - This study tested the hypothesis that the positive inotropic effect of beta
      adrenoceptor stimulation would be inhibited by increases in cyclic GMP in control
      cardiomyocytes and that this response would be modified in hypertrophic
      cardiomyocytes. Cell functional data as well as GMP and cyclic AMP data were
      collected from 7 control and 7 1K1C (one-kidney-one-clip) renal hypertensive
      hypertrophic rabbits. Using isolated control and IKIC ventricular myocytes, data
      were obtained at baseline and after treatment with the beta-adrenoceptor agonist
      isoproterenol (10(-8, -6) mol/l) or the cyclic GMP-phosphodiesterase inhibitor
      zaprinast (10(-5) mol/l) followed by isoproterenol (10(-8, -6) mol/l). We found
      that in control rabbits, isoproterenol (10(-6) mol/l) increased percent
      shortening (4.8 +/- 0.2 to 6.4 +/- 0.3%) and cyclic AMP (2.3 +/- 0.3 to 5.0 +/-
      0.7 pmol/10(5) cells). Zaprinast 10(-5) mol/l increased cyclic GMP (150 +/- 20 to
      209 +/- 14 fmol/10(5) cells) and decreased percent shortening (6.2 +/- 0.4 to 5.2
      +/- 0.3). Zaprinast 10(-5) mol/l prevented the functional response to
      isoproterenol in control (5.2 +/- 0.3 to 4.7 +/- 0.3), without changing cyclic
      AMP levels. In 1K1C rabbits, isoproterenol (10(-6) mol/l) increased cyclic AMP
      (4.9 +/- 0.8 to 7.6 +/- 1.4 pmol/10(5) cells) without changing function.
      Zaprinast 10(-5) mol/l increased cyclic GMP (182 +/- 23 to 233 +/- 24 fmol/10(5)
      cells) and decreased percent shortening (6.6 +/- 0.9 to 4.7 +/- 0.5), but did not
      alter the lack of effect of isoproterenol in 1K1C. In control cardiomyocytes,
      cyclic GMP blunted the isoproterenol contraction response without changing cyclic
      AMP levels, but isoproterenol's functional effect was not seen in 1K1C
      cardiomyocytes.

PMID- 16276123
TI  - Medicare drug therapy in the elderly: pharmacotherapy, politics, and economics at
      the crossroads.

PMID- 16276124
TI  - Medicare Part D: an overview of its practical and clinical impact.
AB  - The Medicare Part D outpatient prescription drug benefit will transform American
      health care delivery. In addition to increasing access to medicines, it will have
      a profound impact on physicians and drug developers. Senior citizens and other
      Medicare recipients will be forced to come to terms with a complex benefit
      structure and to make difficult choices. Physicians will have to help their
      patients navigate the new benefit as well as adjust their practices to deal with
      multiple formularies with different coverage policies. Medicare is creating a
      framework for collecting evidence, both from studies of comparative efficacy of
      drugs and from automated tracking of outcomes.

PMID- 16276125
TI  - Helping Medicare patients benefit from the new Medicare drug benefit: an overview
      with practice tips.
AB  - The new Medicare drug benefit (Part D) will expand drug coverage to the millions
      of Medicare beneficiaries who currently lack insurance protection against the
      costs of prescription drugs. This dramatic expansion of benefits could increase
      medication treatment for many chronic health conditions, but the impact of Part D
      on the affordability of prescription drugs depends on a series of choices
      beneficiaries must make including whether to sign up for the voluntary benefit
      and which of several drug plans to choose. Private prescription drug plans
      administering the benefit will vary in terms of the cost sharing, premiums, and
      formulary design. Providers can play an important role in providing patients with
      the resources necessary to make good choices regarding drug coverage. Medicare
      will also provide reimbursement for medication therapy management. The transition
      of Medicare beneficiaries to Part D drug plans provides an important opportunity
      for providers to review and possibly make changes to their elderly patients' drug
      regimens to maximize effectiveness while minimizing costs to patients.

PMID- 16276126
TI  - The implications of the Medicare Modernization Act for dual eligibles.
AB  - Medicare beneficiaries with incomes at or near the poverty level are also
      eligible for benefits provided by state Medicaid programs. The Medicare
      Modernization Act of 2003 details special provisions for these "dually eligible"
      individuals compared with other Medicare beneficiaries. Issues related to
      enrollment, benefits, and patient compliance are discussed, as well as challenges
      physicians face in caring for this vulnerable population.

PMID- 16276127
TI  - United States pharmacopeia development of the Medicare model formulary
      guidelines.
AB  - Prescription drug formularies are a key element in prescription drug benefit
      management. The use of formularies can both increase the quality of prescribing
      and reduce the costs of prescription drug therapy. The Medicare Prescription
      Drug, Improvement, and Modernization Act of 2003 specified that an external
      agency, the United States Pharmacopeial Convention, Inc. (USP) through the
      Secretary of the United States Department of Health and Human Services develop
      model formulary guidelines for prescription drug plans. The model formulary
      guidelines are to assist individual drug plans in developing formularies that
      would qualify for participation in the Medicare Part D prescription program. The
      guidelines were developed through a Model Guidelines Expert Committee assisted by
      USP staff and following input from patient advocate groups, health care
      organizations, and pharmaceutical organizations over a period of 8 months (April
      2004 to December 2004). The USP Model Formulary Guidelines organize prescription
      medications into 41 therapeutic categories (32 with associated pharmacologic
      classes and nine with no associated pharmacologic classes), 137 pharmacologic
      classes, and 146 unique therapeutic categories and pharmacologic classes.

PMID- 16276128
TI  - The Medicare Part D drug benefit: lessons from the experience with drug discount
      cards.
AB  - The Medicare Modernization Act of 2003 provides federal assistance to eligible
      beneficiaries by paying for their prescription medications. While the full
      program will be implemented in January 2006, a transitional drug discount card
      program has been ongoing since mid-2004. This paper reviews some of the
      operational details of that program and the hurdles created by the complexity of
      the program. By carefully looking back on these hurdles, perhaps one can
      anticipate some of the problems that will likely be encountered when the full
      program is implemented and assist patients in realizing its maximum benefits.

PMID- 16276129
TI  - Experience with providing drugs for seniors in Canada.
AB  - The provincial and territorial governments in Canada are responsible for the
      provision of health care to all Canadians and, as part of this mandate, they
      provide drug coverage to all hospitalized patients regardless of age, and to
      seniors and patients with certain diagnoses, dependent on some forms of means
      testing. The federal government is responsible for regulation and setting
      standards for health care. It provides financial subsidies to the provincial
      programs as well as direct funding for specific groups of individuals. This
      article reviews the roles of each level of government in the provision of
      pharmaceuticals to seniors in Canada.

PMID- 16276130
TI  - What does the Medicare prescription drug legislation mean for the American
      cardiologist?
AB  - The Medicare Modernization Act of 2003 authorized the most sweeping changes to
      the Medicare and Medicaid programs since their inception in 1965. One key
      feature, a prescription drug benefit, will begin enrolling seniors in November
      2005, and the benefit will begin in January 2006. This benefit will have complex
      and largely unknown effects on medication adherence in the elderly. It has a
      complex system of copayments and deductibles and subsidy eligibility
      requirements, as well as a "donut hole." Drug coverage for people dually eligible
      for Medicare and Medicaid will change greatly. Medicare beneficiaries will have
      to choose from a large, bewildering choice of prescription plans and many will
      turn to their physicians for advice. This article details the background,
      benefits, and expected impact of all of these aspects of the new Medicare Part D
      prescription drug benefit.

PMID- 16276131
TI  - Systolic hypertension in older persons: complexities in clinical decision making.
AB  - While the Seventh Report of the Joint National Committee on Prevention,
      Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) challenges
      clinicians to aggressively manage systolic hypertension, few data are available
      to guide clinicians in treating older persons with this condition. In older
      persons, hypertension treatment decisions must often rely on extrapolations and
      fall into a gray area where optimal choice for an individual patient may be
      unclear. In these instances, patients must understand the probable outcomes of
      options, consider the personal value they place on benefits vs. risks, and
      participate with their practitioners in deciding on treatment. Shared decision
      making is the process by which the health care provider and patient share all
      stages of the decision-making process and both discuss treatment preferences and
      agree on a final management plan. Our challenge as clinicians is to ensure that
      all older patients have the opportunity to be treated in a way that is evidence
      based and patient-centered. As with most health care decisions in older persons,
      those regarding blood pressure control should promote evidence-based care that is
      complementary with individualized risk, benefit ratios, patient preferences, and
      treatment goals.

PMID- 16276132
TI  - Ethical issues in the management of geriatric cardiac patients.
AB  - The cardiologist acted in good faith, which resulted in losing the legal battle,
      the support of the hospital administration, and the friendship of the
      pulmonologist.

PMID- 16276133
TI  - Quadricuspid aortic valve with four equal cusps in a quinquagenarian.

PMID- 16276134
TI  - Coronary calcification for cardiovascular risk prediction in the elderly.

PMID- 16276135
TI  - Classic chronic renal failure: hyperkalemia and hypocalcemia.

PMID- 16276136
TI  - Thrombocytopenia following heparin flush.
AB  - A total of 23 patients who developed heparin-induced thrombocytopenia following
      exposure to heparin solely due to intravascular catheter or filter flush were the
      subjects of prospective studies of argatroban therapy. Heparin doses were 10
      13,000 U, with a mean exposure of 8+/-4 days. Following heparin-induced
      thrombocytopenia diagnosis and heparin cessation, 13 patients received argatroban
      (mean dose of 1.8+/-1.1 mg/kg/min for 5.5+/-3.9 days), achieving activated
      partial thromboplastin times of 63+/-23 seconds, and 10 historical control
      patients received no direct thrombin inhibitors. Platelet count recovered to a
      mean of 207+/-153 x 10(9)/L (n=12) after 5.5+/-3.9 days of argatroban therapy and
      to a mean of 127+/-63 x 10(9)/L (n=8) 5 days after baseline in the control group.
      A composite end point of death, amputation, or new thrombosis within 37 days
      occurred in five (38.5%) argatroban-treated patients and four (40%) controls.
      Death was the most common untoward outcome (approximately 30% of each group). No
      argatroban-treated patient and two (20%) control patients experienced new
      thrombosis. Major bleeding was comparable between groups. Heparin-induced
      thrombocytopenia can occur following minimal heparin exposure, including heparin
      flushes; in these patients, argatroban provides effective alternative
      anticoagulation as compared with historical controls.

PMID- 16276138
TI  - Predictors of health status for heart failure patients.
AB  - Health status is poorly understood for patients with heart failure. The purpose
      of this study was to determine the relative importance of relevant
      sociodemographic, clinical, health perception, and emotional variables in
      predicting health status. In this study of 87 patients, health status was
      conceptualized as health-related quality of life, physical activity level, and
      symptom burden. Hierarchical multiple regression was used to determine
      sociodemographic, clinical health perception, and emotional variables associated
      with health status. Worse New York Heart Association class, higher anxiety, and
      higher depression predicted worse health-related quality of life. Better New York
      Heart Association class and higher anxiety predicted higher levels of physical
      activity. Worse New York Heart Association class and higher depression predicted
      greater symptom burden. Traditional demographic and clinical variables were not
      associated with health status. Although not routinely assessed, emotional
      variables had a major impact on health status. Interventions to improve health
      status should target both physical and emotional well-being.

PMID- 16276137
TI  - The impact of exercise on body composition and nutritional intake in patients
      with heart failure.
AB  - Little is known about the nutritional status of heart failure patients and the
      potential synergistic effects between nutritional intake and exercise. This
      small, randomized trial examined the effects of a 3-month exercise program on
      body composition and nutritional intake in 31 men (17 exercisers; 14 controls),
      aged 30-76 years (mean, 56 years) with stable class II-III heart failure.
      Baseline and 3-month evaluations included body mass index, body fat mass by
      triceps skinfold thickness, dietary intake by food frequency questionnaire, and
      the 6-minute walk test. Exercise consisted of walking 3 d/wk and resistance
      exercises 2 d/wk for 40-60 minutes. Dietary recommendations were consistent with
      the American Heart Association/American College of Cardiology heart failure
      guidelines. Exercisers decreased body weight (p=0.001), body mass index
      (p=0.0001), and triceps skinfold thickness (p=0.03) and improved 6-minute walk
      test (p=0.01) compared with controls. Exercisers also demonstrated trends toward
      decreased total caloric and cholesterol intake and a three-fold higher
      carbohydrate, fiber, and beta carotene intake vs. controls. In this study
      population, protein, fiber, and magnesium intake were below recommended daily
      allowance. After exercise, body mass index was reduced, accompanied by dietary
      modifications including greater intake of foods with higher moisture content.
      Further study is needed to investigate the interaction among diet, exercise, and
      weight.

PMID- 16276139
TI  - Using impedance cardiography to assess left ventricular systolic function via
      postural change in patients with heart failure.
AB  - For the diagnosis and management of heart failure, it would be useful to have a
      simple point-of-care test for assessing ventricular function that could be
      performed by a nurse. An impedance cardiography (ICG) parameter called systolic
      amplitude (SA) can serve as an indicator of left ventricular systolic function
      (LVSF). This study tested the hypothesis that patients with normal LVSF should
      have a significant increase in SA in response to an increase in end-diastolic
      volume caused by postural change from sitting upright to supine, while patients
      with depressed LVSF associated with heart failure should have a minimal increase
      or a decrease in SA from upright to supine. ICG data were obtained in 12 patients
      without heart disease and with normal LVSF and 18 patients with clinically
      diagnosed heart failure. Consistent with the hypothesis, patients with normal
      LVSF had a significant increase in SA from upright to supine, whereas heart
      failure patients had a minimal increase or a decrease in SA from upright to
      supine. This ICG procedure may be useful for monitoring the trend of patient
      response to titration of beta blockers and other medications. ICG potentially
      could be used to detect worsening LVSF and provide a means of measurement for
      adjusting treatment.

PMID- 16276141
TI  - Cardiovascular nursing in Norway--on the move.

PMID- 16276140
TI  - Nesiritide for pulmonary arterial hypertension with decompensated cor pulmonale.
AB  - Pulmonary arterial hypertension complicated by decompensated cor pulmonale is a
      challenging clinical problem with few effective therapeutic options. B-type
      natriuretic peptide is a pluripotent hormone that promotes diuresis and
      natriuresis, vasodilates systemic and pulmonary vessels, and reduces circulating
      levels of endothelin and aldosterone. It may represent a possible therapeutic
      strategy for decompensated cor pulmonale in the same manner that it is used to
      treat decompensated left heart failure. The authors report their experience with
      B-type natriuretic peptide as adjunctive therapy for pulmonary arterial
      hypertension complicated by decompensated cor pulmonale. A detailed case report
      is presented followed by the evaluation of a series of 11 cases occurring in
      eight patients from December 2002 through April 2004.

PMID- 16276143
TI  - Exercise capacity in women: a new measure of survival?

PMID- 16276142
TI  - Combination drug therapy in the management of pulmonary arterial hypertension.

PMID- 16276144
TI  - Can pacemakers cause life-threatening arrhythmias?

PMID- 16276145
TI  - Helping families in crisis: listening to and learning from those we serve.

PMID- 16276146
TI  - Barnacles, old age marks, or just plain seborrheic keratoses.

PMID- 16276147
TI  - Dermatology in a primary care practice: the effect of location and demographics
      on medical education in dermatologic disease.

PMID- 16276148
TI  - Patch testing: a retrospective analysis of 103 patients with emphasis on
      practical aspects for the clinician.
AB  - BACKGROUND: Allergic contact dermatitis is a common dermatologic disorder caused
      by small chemical molecules that can penetrate the skin barrier. Thousands of
      chemicals capable of inducing allergic contact dermatitis have been identified.
      To cure allergic contact dermatitis, the allergen should be identified and
      eliminated from the environment of the patient. Patch testing, utilizing a
      variety of standard panels of the most frequent allergens, is used to identify
      the allergen in question. Patch testing is still the gold standard tool used to
      identify one or more substances that may contribute to the etiology of allergic
      contact dermatitis. OBJECTIVE: To determine the frequency of patch test
      positivity and to identify the most common allergens in patients with suspected
      allergic contact dermatitis. METHODS: A retrospective analysis of files of 103
      patients who have been clinically diagnosed to have allergic contact dermatitis
      and have been patch tested using a standard technique with a Northern American
      Contact Dermatitis Group series. RESULTS: Sixty-two patients (60.2%) showed
      positive reactions to one or more substance. The most common allergens were
      nickel sulfate, fragrance mix, and neomycin sulfate. There was an increased
      frequency of positive reactions to fragrance mix and a significant decrease of
      frequency of thimerosal positive reactions. CONCLUSIONS: Increased awareness of
      allergens and their potential sources may help to limit the usage of these
      chemicals in manufacturing consumer products. This may have contributed to
      decreased prevalence rates of certain allergens such as thimerosal and
      paraphenylenediamine.

PMID- 16276149
TI  - A histologic study of adverse effects of different cosmetic skin fillers.
AB  - OBJECTIVE: This study was designed to describe the histologic aspects of the
      cutaneous and mucosal adverse reactions to fillers used for cosmetic purposes.
      METHODS AND MATERIALS: Eleven specimens of adverse reactions caused by Restylane,
      Artecoll, Metacril, New-Fill, Aquamid, and liquid silicone were processed and
      stained by hematoxylin-eosin and Alcian blue and submitted to polarized light.
      RESULTS: Most of the reactions were foreign-body granulomas. CONCLUSIONS: The
      type of granuloma and the characteristics of the agent were determined,
      contributing to the histologic identification of the material used. In the cases
      involving Restylane and Aquamid, it was possible to identify the material using
      Alcian blue stain and by the presence of necrosis. This stain was strongly
      positive in Restylane and faintly positive in Aquamid, and intense necrosis was
      observed in Aquamid cases. In the other cases the filler material itself was
      recognized and identified.

PMID- 16276150
TI  - Skin disease in a primary care practice.
AB  - OBJECTIVE: Family medicine physicians treat a large amount of skin disease. Yet,
      information is lacking regarding which dermatologic disorders are more likely to
      present to a family medicine physician. Therefore, we performed a chart review at
      a family medicine private practice in Islamorada, FL, to determine the percentage
      of patients presenting with dermatologic disease and to identify the most common
      diseases encountered. DISCUSSION: On 12 office days in May 2004 to June 2004, 21%
      of patients seen by a family medicine physician had at least one skin problem,
      which was the chief complaint 72.2% of the time. CONCLUSIONS: Infectious etiology
      and inflammatory conditions accounted for the majority of skin disease diagnosed
      by the physician. Geography and demographics are of great importance when
      considering which dermatologic diseases are most likely to present to a given
      physician.

PMID- 16276151
TI  - Cytokeratins and dermatology.
AB  - Cytokeratins are fibrous intermediate-filament protein polymers present in almost
      all animal cells. Their function is related to epithelium structural maintenance,
      protection from mechanical trauma, and possibly communication between adjacent
      cells or cytoplasm components. Today there are 20 known cytokeratins, classified
      according to their molecular weight and pH as type I or acidic (cytokeratins 9
      20) and type II or neutral-basic (cytokeratins 1-8). Cytokeratins are always
      expressed in specific pairs for each type of tissue, composed of one unit of type
      I and one unit of type II. Primary structural defects of cytokeratins are
      associated with various keratinization impairments. Two of the better
      characterized defects are bullous epidermolysis and epidermolytic hyperkeratosis.
      Anti-cytokeratin monoclonal antibodies are being used for diagnostic purposes to
      characterize the origin of poorly differentiated tumors and metastatic solid
      tumors.

PMID- 16276152
TI  - TNF-alpha inhibitors and congestive heart failure.
AB  - Tumor necrosis factor-alpha inhibitors are among the new class of drugs that
      offer new options for psoriasis control. In addition to serving as a key mediator
      in psoriasis, elevated tumor necrosis factor-alpha levels have also been observed
      in patients with congestive heart failure, and clinical trials have been
      performed to examine the effects of tumor necrosis factor-alpha inhibitors, such
      as etanercept and infliximab, in such a population. Two large-scale trials
      examining the effects of etanercept in more than 2000 patients with heart failure
      did not indicate any increased risk of mortality or morbidity, and no US Food and
      Drug Administration warning has been issued regarding the use of etanercept in
      such a patient population. On the other hand, a study with infliximab showed
      significantly increased deaths, hospitalizations, and morbidity. Thus,
      infliximab>5 mg/kg is now contraindicated in patients with moderate-to-severe
      congestive heart failure (New York Heart Association functional class III/IV). If
      infliximab must be used, it should not exceed 5 mg/kg, and patients must be
      followed closely.

PMID- 16276154
TI  - Benzoyl peroxide skin washes: basis, logic, effectiveness, and tolerance.

PMID- 16276153
TI  - Atopiclair nonsteroidal cream.

PMID- 16276156
TI  - Risk assessment of variant Creutzfeldt-Jakob disease in cosmetics.

PMID- 16276155
TI  - A practical comparison of hydroquinone-containing products for the treatment of
      melasma.

PMID- 16276157
TI  - Perioperative management of patient expectations.

PMID- 16276159
TI  - Photo capsules-tuberculosis mastitis.

PMID- 16276158
TI  - The gift that keeps on giving.
AB  - Case 1: A 39-year-old man with chronic lower extremity lymphedema was admitted to
      the hospital with acute fever, chills, and left lower extremity pain, swelling,
      and erythema for the third time in as many months. Examination revealed a
      temperature of 39 degrees C (102.2 degrees F), and erythmatous induration on the
      left leg (Figure). The patient was treated with IV clindamycin and cefazolin,
      with clinical improvement. He was discharged with azithromycin, 500 mg daily for
      3 days, done twice monthly. Case 2: A 52-year-old morbidly obese man with stasis
      dermatitis presented with acute lower extremity pain, swelling, and associated
      fever. He had been taking prophylactic antibiotics for his recurrent cellulitis
      for more than a decade and had significantly decreased his number of
      reoccurrences while on this therapy. He was admitted to the hospital, treated
      with IV cefazolin, and had a rapid improvement over 48 hours. He was subsequently
      discharged with continued suppressive antibiotic therapy.

PMID- 16276160
TI  - Preparing the skin before injecting botulinum toxin--more myth than evidence
      based good judgment.

PMID- 16276162
TI  - Cheilitis glandularis in an African-American woman: response to antibiotic
      therapy.
AB  - A 52-year-old black woman presented with a 2-day history of lower lip swelling 5
      days after starting a new medication, lisinopril. She had never experienced
      similar episodes in the past. She denied shortness of breath, tightening of the
      throat, swelling of the tongue, generalized cutaneous eruption, urticaria, or
      pruritus. She also denied symptoms consistent with facial paresis. Her past
      medical history was significant for hepatitis C infection, coronary artery
      disease, and hypertriglyceridemia. She had a 15 pack-year smoking history and
      denied both alcohol and drug abuse. She had never received a blood transfusion
      and was HIV negative. Physical examination disclosed a tender, swollen, and
      erythematous lower lip with induration, oozing, and crusting (Figure 1). Pinpoint
      openings evident throughout the lip surface exuded a clear, sticky, mucoid
      secretion. Tongue, parotid glands, and regional lymph nodes were normal. The
      working diagnosis was angioedema secondary to lisinopril. The presumptive
      offending drug was discontinued, and conservative therapy (topical clobetasol
      ointment, oral ranitidine, and oral fexofenadine) was initiated. Despite
      treatment, signs and symptoms persisted unabated. One week after initial
      presentation, a punch biopsy of her lower lip was taken to rule out granulomatous
      cheilitis and sarcoidosis. Histopathology included diffuse lymphohistiocytic
      infiltrate, minimal microabscess formation, and notable absence of granulomata.
      There was neither hypertrophy nor detectable abnormality of the salivary glands,
      with the exception of infiltrating mononuclear cells. Based on the clinical
      history and compatible pathologic findings, a diagnosis of cheilitis glandularis
      was made. Specifically, crusting and erosion clinically suggested a diagnosis of
      the superficial suppurative subtype of cheilitis glandularis. The patient
      received oral penicillin (dicloxacillin, 1.0 g/d) combined with oral
      fluoroquinolone (ciprofloxacin, 1.0 g/d). Within 2 weeks of starting the
      antibiotics, the lip swelling significantly decreased (Figure 2) and the patient
      was left with a mildly indurated nodule at the labial commissure. Following a 4
      week course of continued antibiotic treatment, the lip returned to near baseline
      state. At both 6-month and 1-year follow-up visits, the lip remained normal.

PMID- 16276161
TI  - Improvement in psoriasis with rosiglitazone in a diabetic and a nondiabetic
      patient.
AB  - The authors conducted a prospective, open-label, pilot trial of the effects of
      the antidiabetic thiazolidinedione (TZD) rosiglitazone in two patients with
      moderate to severe plaque psoriasis. Case 1: A lean, euglycemic 43-year-old
      nondiabetic man with a 2-year history of plaque psoriasis presented with lesions
      involving 10% of his body surface (Figures 1A, 1B, 1C). He had no other chronic
      or acute medical problems. He had previously been managed sporadically with
      topical triamcinolone acetonide, an intermediate-strength glucocorticoid, and was
      off antipsoriatic medication for 5 months. He was started on rosiglitazone p.o.,
      8 mg q.d. After 10 weeks on rosiglitazone, the lesions developed increased
      erythema, spreading, and shedding of scale (Figures 2A, 2B, 2C). After an
      additional 26 weeks, the lesions had largely disappeared (Figures 3A, 3B, 3C).
      The patient remained euglycemic throughout the study. His liver function enzymes
      (alanine transferase [ALT] and aspartate transferase [AST]) remained normal
      throughout the study: ALT, 23 IU/L; AST, 47 IU/L before treatment; ALT, 25 IU/L;
      AST, 33 IU/L after treatment. There were no adverse events. Case 2: An overweight
      68-year-old woman (body mass index, 29 kg/m2; with a 12-year history of type 2
      diabetes and 5-year history of psoriasis presented with generalized plaque
      psoriasis over 20% of her body, including two large, thick, silvery plaques with
      the texture of leather over the lower part of the back (Figure 4A). She was given
      rosiglitazone p.o., 4 mg b.i.d. for 24 weeks, which resulted in significant
      improvement in psoriasis (Figure 4B). After an additional 26 weeks on
      rosiglitazone, the plaques had cleared on her back (Figure 4C) and over her
      entire body, including scalp, ears, and posterior forearms (not shown). Her
      glycemic control improved (hemoglobin A1c decreased from 7.7% to 7.2%) and liver
      function remained normal throughout the study (ALT, 24 IU/L; AST, 14 IU/L before
      treatment; and ALT, 26 IU/L; AST, 15 IU/L after treatment). There were no adverse
      events.

PMID- 16276163
TI  - Intralesional methotrexate for keratoacanthoma of the nose.
AB  - A 56-year-old woman developed a nodule on her nose. A shave biopsy of the
      enlarging lesion was performed after 2 weeks and showed a keratoacanthoma. During
      the subsequent 4 weeks, the lesion continued to grow rapidly, and she was
      referred for excision of the lesion using the Mohs microscopically controlled
      technique. A tender 10x12 mm (120 mm2) erythematous nodule with a keratin-filled
      central umbilication was present on her left nasal ala (Figure 1). Treatment
      options were discussed. The left nasal ala was locally anesthetized with 1%
      lidocaine with 1:100,000 epinephrine and the keratoacanthoma was
      circumferentially infiltrated with 10 mg of methotrexate (0.8 mL of 12.5 mg/mL
      methotrexate) using a 30-gauge needle. The total amount of methotrexate injected
      was divided among several injection sites: the peripheral shoulder of the lesion
      (such that there was blanching of the entire rim) and under the center of the
      lesion at a depth clinically judged to be the deepest area of involvement. Within
      the next 7 days, the tumor began to decrease in size and ulcerate centrally.
      Examination 2 weeks after the initial injection showed a 71% reduction in the
      area of the tumor, which now measured 35 mm2 (7.0x5.0 mm). The tumor was injected
      in a similar manner as before with 5 mg of methotrexate. After another 2 weeks,
      the tumor had continued to shrink. It was flat without nodularity and measured 12
      mm2 (4.0x3.0 mm); the tumor area was 66% less than 2 weeks earlier and 90% less
      than its original size. The residual tumor was again injected with 4.5 mg of
      methotrexate. There was complete clinical involution of the tumor when the
      patient returned for evaluation 6 weeks after her initial injection of
      methotrexate (Figure 2). A biopsy of the lesional area to confirm histologic
      resolution of the keratoacanthoma was not performed since there was no visible
      residual tumor. Periodic follow-up examination has been performed and there has
      been no subsequent recurrence of the keratoacanthoma.

PMID- 16276164
TI  - Pre-ejection period variations predict the fluid responsiveness of septic
      ventilated patients.
AB  - OBJECTIVES: In septic patients with acute circulatory failure, reliable
      predictors of fluid responsiveness are needed at the bedside. We hypothesized
      that the respiratory change in pre-ejection period (DeltaPEP) would allow the
      prediction of changes in cardiac index following volume administration in
      mechanically ventilated septic patients. DESIGN: Prospective clinical
      investigation. SETTING: A ten-bed hospital intensive care unit. PATIENTS:
      Patients admitted after septic shock equipped with an arterial catheter.
      INTERVENTIONS: Pre-ejection period (PEP)--defined as the time interval between
      the beginning of the R wave on the electrocardiogram and the upstroke of the
      radial arterial pressure curve (PEPKT) or the pulse plethysmographic waveforms
      (PEPPLET)--and cardiac index (transthoracic echocardiography-Doppler) were
      determined before and after volume infusion of colloid (8 mL x kg). DeltaPEP (%)
      was defined as the difference between expiratory and inspiratory PEP divided by
      the mean of expiratory and inspiratory values. Respiratory changes in pulse
      pressure (DeltaPP) was also measured. MEASUREMENTS AND MAIN RESULTS: : Twenty-two
      volume challenges were done in 20 deeply sedated patients. DeltaPEPKT,
      DeltaPEPPLET, and DeltaPP (measured in all patients) before volume expansion were
      correlated with cardiac index change after fluid challenge (r = .73, r = .67, and
      r = .70, respectively, p < .0001). Patients with a cardiac index increase induced
      by volume expansion > or = 15% and <15% were classified as responders and
      nonresponders, respectively. Receiver operating characteristic curves showed that
      the threshold DeltaPP value of 17% allowed discrimination between
      responder/nonresponder patients with a sensitivity of 85% and a specificity of
      100%. For both DeltaPEPKT and DeltaPEPPLET, the best threshold value was 4% with
      a sensitivity-specificity of 92%-89% and 100%-67%, respectively. CONCLUSIONS: The
      present study found DeltaPEPKT and DeltaPEPPLET to be as accurate as DeltaPP in
      the prediction of fluid responsiveness in mechanically ventilated septic
      patients.

PMID- 16276165
TI  - Prophylactic fenoldopam for renal protection in sepsis: a randomized, double
      blind, placebo-controlled pilot trial.
AB  - OBJECTIVE: Acute renal failure is common in septic patients. Fenoldopam, a
      dopamine-1 receptor agonist, increases renal blood flow and may, therefore,
      reduce the risk of acute renal failure in such patients. Accordingly, we sought
      to determine the safety and efficacy of fenoldopam for the prevention of acute
      renal failure in septic patients. DESIGN: Prospective, double-blind, placebo
      controlled trial. SETTING: Three multidisciplinary intensive care units at a
      university hospital. PATIENTS: Three hundred septic patients with baseline serum
      creatinine concentrations <150 micromol/L. INTERVENTIONS: We randomized patients
      to a continuous infusion of either fenoldopam (n = 150) at 0.09 microg x kg x min
      or placebo (n = 150) while in the intensive care unit. The primary outcome
      measure was the incidence of acute renal failure, defined as a serum creatinine
      concentration increase to >150 micromol/L, during study drug infusion.
      MEASUREMENTS AND MAIN RESULTS: The incidence of acute renal failure was
      significantly lower in the fenoldopam group compared with the control group (29
      vs. 51 patients; p = .006). The odds ratio of developing acute renal failure for
      patients treated with fenoldopam was estimated to be 0.47 (p = .005). The
      difference in the incidence of severe acute renal failure (creatinine >300
      mumol/L), however, failed to achieve statistical significance (10 vs. 21; p =
      .056). The length of intensive care unit stay in surviving patients was
      significantly lower in the fenoldopam group compared with the control group
      (10.64 +/- 9.3 vs. 13.4 +/- 14.0; p < .001). There were no complications of
      fenoldopam infusion. A direct effect of treatment on the probability of death,
      beyond its effect on acute renal failure, was not significant (odds ratio = 0.68,
      p = .1). CONCLUSIONS: Compared with placebo, low-dose fenoldopam resulted in a
      smaller increase in serum creatinine in septic patients. The clinical
      significance of this finding is uncertain. A large multiple-center trial is now
      needed to confirm these findings.

PMID- 16276166
TI  - Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in
      early hyperdynamic septic shock.
AB  - OBJECTIVES: To investigate the effect of low-dose hydrocortisone on time to shock
      reversal, the cytokine profile, and its relation to adrenal function in patients
      with early septic shock. DESIGN: Prospective, randomized, double-blind, single
      center study. SETTING: Medical intensive care unit of a university hospital.
      PATIENTS: Forty-one consecutive patients with early hyperdynamic septic shock.
      INTERVENTIONS: After inclusion and a short adrenocorticotropic hormone test, all
      patients were randomized to receive either low-dose hydrocortisone (50-mg bolus
      followed by a continuous infusion of 0.18 mg/kg body of weight/hr) or matching
      placebo. After shock reversal, the dose was reduced to 0.06 mg/kg/hr and
      afterward slowly tapered. Severity of illness was estimated using Acute
      Physiology and Chronic Health Evaluation II score and Sequential Organ Failure
      Assessment score. MEASUREMENTS AND MAIN RESULTS: Time to cessation of vasopressor
      support (primary end point) was significantly shorter in hydrocortisone-treated
      patients compared with placebo (53 hrs vs. 120 hrs, p < .02). This effect was
      more profound in patients with impaired adrenal reserve. Irrespective of
      endogenous steroid production, cytokine production was reduced in the treatment
      group with lower plasma levels of interleukin-6 and a diminished ex vivo
      lipopolysaccharide-stimulated interleukin-1 and interleukin-6 production.
      Interleukin-10 levels were unaltered. Adverse events were not more frequent in
      the treatment group. CONCLUSIONS: Treatment with low-dose hydrocortisone
      accelerates shock reversal in early hyperdynamic septic shock. This was
      accompanied by reduced production of proinflammatory cytokines, suggesting both
      hemodynamic and immunomodulatory effects of steroid treatment. Hemodynamic
      improvement seemed to be related to endogenous cortisol levels, whereas immune
      effects appeared to be independent of adrenal reserve.

PMID- 16276167
TI  - Noninvasive ventilation to prevent respiratory failure after extubation in high
      risk patients.
AB  - OBJECTIVE: Compared with standard medical therapy (SMT), noninvasive ventilation
      (NIV) does not reduce the need for reintubation in unselected patients who
      develop respiratory failure after extubation. The goal of this study was to
      assess whether early application of NIV, immediately after extubation, is
      effective in preventing postextubation respiratory failure in an at-risk
      population. DESIGN: Multiple-center, randomized controlled study. SETTING:
      Multiple hospitals. PATIENTS: Ninety-seven consecutive patients with similar
      baseline characteristics, requiring >48 hrs of mechanical ventilation and
      considered at risk of developing postextubation respiratory failure (i.e.,
      patients who had hypercapnia, congestive heart failure, ineffective cough and
      excessive tracheobronchial secretions, more than one failure of a weaning trial,
      more than one comorbid condition, and upper airway obstruction). INTERVENTIONS:
      After a successful weaning trial, the patients were randomized to receive NIV for
      > or = 8 hrs a day in the first 48 hrs or SMT. Primary outcome was the need for
      reintubation according to standardized criteria. Secondary outcomes were
      intensive care unit and hospital mortality, as well as time spent in the
      intensive care unit and in hospital. MEASUREMENTS AND MAIN RESULTS: Compared with
      the SMT group, the NIV group had a lower rate of reintubation (four of 48 vs. 12
      of 49; p = .027). The need for reintubation was associated with a higher risk of
      mortality (p < .01). The use of NIV resulted in a reduction of risk of intensive
      care unit mortality (-10%, p < .01), mediated by the reduction for the need of
      reintubation. CONCLUSIONS: NIV was more effective than SMT in preventing
      postextubation respiratory failure in a population considered at risk of
      developing this complication.

PMID- 16276168
TI  - Intrahospital transport of critically ill ventilated patients: a risk factor for
      ventilator-associated pneumonia--a matched cohort study.
AB  - OBJECTIVE: To evaluate the impact of intrahospital transport of critically ill
      ventilated patients on the acquisition of ventilator-associated pneumonia.
      DESIGN: An exposed/unexposed matched cohort study. SETTING: An 18-bed adult
      medical-surgical intensive care unit in a 1,100-bed regional and teaching
      hospital in France. PATIENTS: From January 1, 2001, to December 31, 2002, 118 of
      228 ventilated patients transported out of the intensive care unit (exposed
      patients) were matched with 118 unexposed patients selected among 295 ventilated
      patients who did not undergo intrahospital transport. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The matching process was conducted according to
      six criteria: duration of mechanical ventilation, duration of antibiotherapy,
      indication for ventilatory support, age, probability of death, and surgical
      procedures or not during intensive care unit stay. The rates of ventilator
      associated pneumonia (as defined by usual clinical and biological criteria plus
      positive culture of bronchoscopy directed catheter) acquisition between exposed
      and unexposed patients were compared by univariate analysis and then by
      multivariate analysis (conditional logistic regression and Cox's proportional
      hazards model) to account for potential confounding factors. The ventilator
      associated pneumonia rate was 26% in exposed patients compared with 10% in the
      matched unexposed patients. Using conditional logistic regression, two factors
      were independently associated with ventilator-associated pneumonia: intrahospital
      transport (odds ratio, 3.1; 95% confidence interval, 1.4-6.7) and the need for
      reintubation. Using Cox's model, three independent risk factors were identified:
      the need for reintubation, enteral nutrition, and intrahospital transport (odds
      ratio, 2.9; 95% confidence interval, 1.4-5.7). The intensive care unit mortality
      rate was similar (p > .1) in exposed (35%) and unexposed patients (26%).
      CONCLUSIONS: Intrahospital transport appears to be a significant risk factor for
      ventilator-associated pneumonia. However, the respective roles of intrahospital
      transport and of the cause that leads clinicians to transport patients (mainly
      for radiographic examinations) are difficult to dissociate even after multiple
      statistical adjustments. When intrahospital transport is needed, very cautious
      measures must be taken before and during intrahospital transport to prevent
      ventilator-associated pneumonia. In addition, in the few days after intrahospital
      transport, intensive search for ventilator-associated pneumonia is justified.

PMID- 16276169
TI  - Relative adrenal insufficiency in patients with septic shock: comparison of low
      dose and conventional corticotropin tests.
AB  - OBJECTIVE: To compare a low-dose (1 microg) corticotropin stimulation test with
      the more standard (250 microg) test for the diagnosis of relative adrenal
      insufficiency. DESIGN: Diagnostic study. SETTING: Thirty-one-bed mixed medico
      surgical department of intensive care. PATIENTS: Forty-six consecutive patients
      with septic shock. INTERVENTIONS: Corticotropin stimulation tests (low-dose test,
      1 microg, and standard 250-microg test), performed consecutively at an interval
      >4 hrs. MEASUREMENTS AND MAIN RESULTS: In each test, serum cortisol levels were
      measured before (T0) and 30 (T30), 60 (T60), and 90 (T90) mins after
      corticotropin injection. The maximal increase in cortisol (Deltamax) was
      calculated as the difference between T0 and the highest cortisol value at T30,
      T60, or T90 and considered as adequate if >9 microg/dL (250 nmol/L).
      Nonresponders to the low-dose test had a lower survival rate than responders to
      both tests (27 vs. 47%, p = .06; Kaplan Meier curves). Interestingly,
      nonresponders to high-dose test received hydrocortisone treatment and had a
      similar survival to responders. Multivariable logistic regression disclosed that
      the response to the combined low-dose test and high-dose test was an independent
      predictor of survival (odds ratio 28.91, 95% confidence interval 1.81-462.70, p =
      .017), whereas basal or maximal cortisol levels in both tests were not.
      CONCLUSIONS: The low-dose test identified a subgroup of patients in septic shock
      with inadequate adrenal reserve who had a worse outcome and would have been
      missed by the high-dose test. These patients may also benefit from glucocorticoid
      replacement therapy.

PMID- 16276171
TI  - Intensive care in patients with newly diagnosed malignancies and a need for
      cancer chemotherapy.
AB  - OBJECTIVE: Patients with newly diagnosed cancer responsible for organ failures
      may require intensive care unit (ICU) admission and immediate chemotherapy.
      Outcomes in this population have not been studied. DESIGN: Prospective
      observational cohort study. SETTING: Teaching hospital. SUBJECTS: All patients
      admitted to the ICU, from January 1997 to June 2003, for organ failures due to
      newly diagnosed, untreated cancer and deemed necessary to receive immediate
      cancer chemotherapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the
      period of 6.5 yrs, 100 patients met the study criteria: 43 had acute leukemia, 37
      lymphoma, and 12 solid tumors. Median Simplified Acute Physiology Score II was 39
      (30-48) points, and median Logistic Organ Dysfunction score was 5 (3-7) points.
      Three variables were independently associated with 30-day mortality: need for
      vasopressor therapy (odds ratio, 6.01; 95% confidence interval, 1.86-19.4),
      mechanical ventilation (odds ratio, 6.36; 95% confidence interval, 1.76-22.94);
      and hepatic failure (odds ratio, 7.76; 95% confidence interval, 1.25-48.27).
      Overall survival was 60% after 30 days and 49% after 180 days. CONCLUSIONS:
      Mortality was chiefly dependent on the nature and number of organ failures, not
      on the nature or stage of the malignancy. The 30-day and 180-day survival rates
      indicate that, in this selected group of patients, advanced disease at cancer
      diagnosis should not lead to refusal of ICU admission. Moreover, administration
      of chemotherapy in the intensive care unit is feasible, and although the
      mortality rate is high, routine ICU admission of patients with newly diagnosed
      cancer, specific organ failure, and the need for administration of chemotherapy
      in the ICU deserves evaluation.

PMID- 16276172
TI  - Monitoring global volume-related hemodynamic or regional variables after initial
      resuscitation: What is a better predictor of outcome in critically ill septic
      patients?
AB  - OBJECTIVE: Regional variables of organ dysfunction are thought to be better
      monitoring variables than global pressure-related hemodynamic variables. Whether
      a difference exists between regional and global volume-related variables in
      critically ill patients after resuscitation is unknown. DESIGN: Prospective
      diagnostic test evaluation. SETTING: University-affiliated mixed intensive care
      unit. PATIENTS: Twenty-eight critically ill patients. INTERVENTIONS: Using
      standardized resuscitation, hemodynamic optimization was targeted at mean
      arterial pressure, heart rate, occlusion pressure, cardiac output, systemic
      vascular resistance, and urine output. Primary outcome variable was in-hospital
      mortality. MEASUREMENTS AND MAIN RESULTS: During resuscitation, global volume
      related hemodynamic variables were measured simultaneously and compared with
      regional variables. At admission no variable was superior as a predictor of
      outcome. During resuscitation, significant changes were seen in mean arterial
      pressure, central venous pressure, oxygen delivery, systemic vascular resistance,
      total blood volume, right heart and ventricle end-diastolic volume, right
      ventricle ejection fraction, right and left stroke work index, intramucosal
      carbon dioxide pressure, gastric mucosal pH, mucosal-end tidal Pco2 gap,
      indocyanine green blood clearance, indocyanine green plasma clearance, and plasma
      disappearance rate. Multivariate analysis identified lactate, gastric mucosal pH,
      mucosal-end tidal Pco2 gap, mucosal-arterial Pco2 gap, indocyanine green plasma
      clearance, and plasma disappearance rate of dye as nondependent predictors of
      outcome. Patients who subsequently died had a significantly lower gastric mucosal
      pH, higher intramucosal carbon dioxide pressure and mucosal-end tidal Pco2 gap,
      and lower indocyanine green blood clearance, indocyanine green plasma clearance,
      plasma disappearance rate, and right ventricular end-diastolic volume index, of
      which gastric mucosal pH, mucosal-end tidal Pco2 gap, and indocyanine green blood
      clearance were the most important predictors of outcome. CONCLUSIONS: Initial
      resuscitation of critically ill patients with shock does not require monitoring
      of regional variables. After stabilization, however, regional variables are the
      best predictors of outcome.

PMID- 16276173
TI  - Does the addition of glutamine to enteral feeds affect patient mortality?
AB  - OBJECTIVE: Studies have failed to consistently demonstrate improved survival in
      intensive care unit (ICU) patients receiving immune-modulating nutrient-enhanced
      enteral feeds when compared with standard enteral feeds. The objective was to
      study in a prospective fashion the effects of adding glutamine to standard or
      immune-modulated (supplemented with omega-3 fatty acids, beta-carotene, and amino
      acids such as glutamine and arginine) tube feeds. DESIGN: Prospective, unblinded
      study using sequential allocation. SETTING: A university surgical trauma ICU.
      PATIENTS: All surgical and trauma patients admitted to the surgical trauma ICU at
      a university hospital over a 3-yr period who were to receive enteral feeds (n =
      185). INTERVENTIONS: Sequential assignment to three isocaloric, isonitrogenous
      diets was performed as follows: standard 1-kcal/mL feeds with added protein
      (group 1), standard feeds with the addition of 20-40 g/day (0.6 g/kg/day)
      glutamine (group 2), or an immune-modulated formula with similar addition of
      glutamine (group 3). The goal for all patients was 25-30 kcal/kg/day and 2
      g/kg/day protein. MEASUREMENTS AND MAIN RESULTS: Patients were followed until
      discharge from the hospital. The primary end point was in-hospital mortality, and
      multiple secondary end points were recorded. In-hospital mortality for group 1
      was 6.3% (four of 64) vs. 16.9% (ten of 59, p = .09) for group 2 and 16.1% (ten
      of 62, p = .09) for group 3. After controlling for age and severity of illness,
      the difference in mortality between patients receiving standard tube feeds and
      all patients receiving glutamine was not significant (p < or = .11). There were
      no statistically significant differences between the groups for secondary end
      points. CONCLUSIONS: The addition of glutamine to standard enteral feeds or to an
      immunomodulatory formula did not improve outcomes. These findings suggest that
      enteral glutamine should not be routinely administered to patients with surgical
      critical illness.

PMID- 16276174
TI  - Effect of low-calorie parenteral nutrition on the incidence and severity of
      hyperglycemia in surgical patients: a randomized, controlled trial.
AB  - OBJECTIVE: To determine the effect of a low-calorie parenteral nutrition (PN)
      regimen on the incidence and severity of hyperglycemia and insulin requirements.
      DESIGN: Prospective, randomized, clinical trial. SETTING: Urban, university
      affiliated, level-I trauma center. PATIENTS: Consecutive surgical patients
      requiring PN. INTERVENTIONS: Patients were randomized to receive either a low
      calorie PN formulation (20 nonprotein kilocalories per kg per day) or a standard
      PN formulation (30 nonprotein kilocalories per kg per day). Lipid-derived
      calories were standardized to 1000 kilocalories three times weekly for all
      patients; consequently, the number of calories varied only by the amount of
      carbohydrate administered. Protein requirements were individualized on the basis
      of estimated metabolic stress. Hyperglycemia was defined as a blood glucose level
      > or = 200 mg/dL. MEASUREMENTS AND MAIN RESULTS: Forty patients were evaluated
      (low-calorie PN, n = 20; standard PN, n = 20). Demographics of the two groups
      were similar. The incidence of hyperglycemic events was significantly lower in
      the low-calorie group (0% [0-0.5] vs. 33.1% [0-58.4]; p = .001]. Additionally,
      the severity of hyperglycemia was also lower in the low-calorie group (mean
      glucose area under the curve = 118 +/- 22 [mg x hr]/dL vs. 172 +/- 44 [mg x
      hr]/dL; p < .001). This resulted in lower average daily insulin requirements (0
      [0-0] units vs. 10.9 [0-25.6] units; p < .001.). The only predictor of
      hyperglycemia was a dextrose administration rate >4 mg/kg/min. CONCLUSIONS: :
      Administration of a low-calorie PN formulation resulted in fewer and less-severe
      hyperglycemic events and lower insulin requirements. PN regimens should not
      exceed a dextrose administration rate of 4 mg/kg/min to avoid hyperglycemic
      events.

PMID- 16276175
TI  - Relationship between tracheostomy timing and duration of mechanical ventilation
      in critically ill patients.
AB  - OBJECTIVE: Tracheostomy practice in the setting of critical illness is
      controversial because evidence demonstrating unequivocal benefit is lacking. We
      undertook this study to determine the relationship between tracheostomy timing
      and duration of mechanical ventilation, intensive care unit length of stay, and
      hospital length of stay and to evaluate the relative influence of clinical and
      nonclinical factors on tracheostomy practice. DESIGN: Analysis of Project Impact,
      a multi-institutional critical care administrative database. SETTING: Medical
      school. PATIENTS: Data from 43,916 patients were reviewed. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Tracheostomy was performed in 2,473 (5.6%) of
      43,916 patients analyzed. Tracheostomy patients had a higher survival rate than
      nontracheostomy patients (78.1 vs. 71.7%, p < .001) and underwent this procedure
      following a median (25th-75th percentile) of 9.0 (5.0-14.0) days of ventilatory
      support. Tracheostomy frequency and timing varied significantly comparing
      patient, intensive care unit, and hospital characteristics (p < .05 for all).
      Tracheostomy timing correlated significantly with duration of mechanical
      ventilation (r = .690), intensive care unit (r = .610), and hospital length of
      stay (r = .341, p < .001 for all). At most, 22% of patients were supported via
      tracheostomy at any given time. Although a minority, tracheostomy patients
      accounted for 26.2%, 21.0%, and 13.5% of all ventilator, intensive care unit, and
      hospital days, respectively. CONCLUSIONS: Although practice varies substantially,
      tracheostomy timing appears significantly associated with duration of mechanical
      ventilation, intensive care unit length of stay, and hospital length of stay.
      These findings emphasize the need for an adequately supported multiple-center
      trial to better define patient selection for tracheostomy and to test the
      hypothesis that timing of this procedure influences clinically important
      outcomes.

PMID- 16276176
TI  - APOE polymorphism is associated with risk of severe sepsis in surgical patients.
AB  - OBJECTIVE: To test for an association between apolipoprotein E (APOE) genotypes
      and the occurrence of severe sepsis in an elective surgical cohort. DESIGN:
      Prospective, observational, single cohort study. SETTING: Sixteen-bed surgical
      intensive care unit (ICU) at a university hospital. PATIENTS: Patients were 343
      patients with planned admission to the ICU after major elective noncardiac
      surgery. INTERVENTIONS: Blood samples, together with demographic data, baseline
      clinical data, and Acute Physiology and Chronic Health Evaluation II scores, were
      collected on admission to the ICU and on each subsequent ICU day. APOE genotyping
      was conducted using a polymerase chain reaction-based assay. The primary outcome
      was diagnosis of severe sepsis; secondary outcomes included time on mechanical
      ventilation, ICU length of stay, and ICU mortality. MEASUREMENTS AND MAIN
      RESULTS: Severe sepsis was diagnosed in 34 of 343 patients (9.9%). Carriers of
      the APOepsilon3 allele (one or two copies) had a lower incidence of severe sepsis
      than patients with no APOepsilon3 allele (p = .014), with a relative risk of
      0.284 (95% confidence interval 0.127-0.635). The protective effect of APOepsilon3
      genotype on the incidence of severe sepsis remained significant (p < .01) after
      adjusting for age, gender, or race in a logistic regression model. Supporting our
      findings, presence of the APOepsilon3 allele was also associated with fewer days
      spent in the ICU (p = .007). In contrast, APOE genotypes were not associated with
      duration of mechanical ventilation or ICU mortality. CONCLUSIONS: In an elective
      surgical cohort, presence of the APOepsilon3 allele is associated with decreased
      incidence of severe sepsis and a shorter ICU length of stay.

PMID- 16276177
TI  - Impact of tracheotomy on sedative administration, sedation level, and comfort of
      mechanically ventilated intensive care unit patients.
AB  - OBJECTIVE: To assess the impact of tracheotomy on sedative administration,
      sedation level, and autonomy of mechanically-ventilated intensive care unit (ICU)
      patients. DESIGN, SETTING, AND PATIENTS: In this observational study, the charts
      of all consecutive patients undergoing mechanical ventilation requiring
      tracheotomy over a 14-month period in our 18-bed tertiary care ICU were reviewed
      retrospectively. Patients' sedation levels (according to the Riker's 7-level
      sedation-agitation score) and intravenous (fentanyl and midazolam) and oral
      (clorazepate and haloperidol) sedative administration were measured daily during
      the 7 days before and after tracheotomy. We also recorded patients for whom chair
      positioning and oral alimentation became possible in the days following
      tracheotomy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Tracheotomy was
      performed on 72 (23.1%) of the 312 patients undergoing mechanical ventilation for
      > or = 48 hrs. After tracheotomy, median (25th, 75th percentiles) fentanyl and
      midazolam administration decreased from 866 (191, 1672) to 71 (3, 426)
      microg/(patient.day) and from 44 (16, 128) to 7 (1, 42) mg/(patient.day) (p <
      .001), respectively. Concomitant median time spent heavily sedated decreased from
      7 (3, 17) to 1 (0, 6) hrs/day (p < .001), with no increase in agitation time.
      During the 7 days following tracheotomy, partial oral alimentation became
      possible for 35 patients (48.6%) and out-of-bed positioning became possible for
      16 patients (22.2%). CONCLUSION: On the basis of these observations, we conclude
      that tracheotomized mechanically ventilated ICU patients required less
      intravenous sedative administration, spent less time heavily sedated, and
      achieved more autonomy earlier.

PMID- 16276178
TI  - Levels of endothelial and platelet microparticles and their interactions with
      leukocytes negatively correlate with organ dysfunction and predict mortality in
      severe sepsis.
AB  - OBJECTIVE: Mortality in sepsis is believed to be associated with exaggerated
      inflammatory responses, but recent evidence suggests that poor outcome is
      associated with reduced inflammation. To test this hypothesis, we measured
      several inflammatory markers to determine whether any of them or any combinations
      are associated with mortality or organ dysfunction. DESIGN: Clinical study.
      SETTING: School of medicine. PATIENTS: Thirty-five patients with severe sepsis.
      INTERVENTIONS: Markers of endothelial, platelet, and leukocyte activation were
      measured on days 1, 2, and 3 after enrollment. The markers were a) endothelial
      microparticles (EMPs) and their conjugates with monocytes (EMP/MONO); b) platelet
      microparticles (PMPs) and platelet activation marker CD62P; c) platelet-leukocyte
      conjugates (PLT/LEU) and leukocyte activation marker CD11b; and d) intracellular
      nitric oxide in leukocytes. MEASUREMENTS AND MAIN RESULTS: The 28-day mortality
      rate was 51% (18 of 35). Significant differences between survivors and
      nonsurvivors on day 1 were found in PLT/LEU (p = .001), CD11b (p = 0.02), and
      EMP/MONO (p = .02) groups. Using logistic regression to assess if these markers
      predict mortality on day 1, we found that PLT/LEU had the best predictive value
      among the markers used (area under receiver operating characteristics curve =
      0.82). All markers of cell activation and inflammation were significantly higher
      among survivors on days 2 and 3, except nitric oxide, which was lower. This
      marker showed significant negative correlation with the Sequential Organ Failure
      Assessment score throughout the study. CONCLUSIONS: Our data support the
      hypothesis that early increased, not decreased, inflammatory response as measured
      by our markers is associated with improved survival rate. A high negative
      correlation was found between some of these markers and Sequential Organ Failure
      Assessment score.

PMID- 16276179
TI  - Measurement of pulmonary edema in patients with acute respiratory distress
      syndrome.
AB  - OBJECTIVE: We measured pulmonary edema by thermal indocyanine green-dye double
      dilution technique and quantitative computed tomography (CT) in patients with
      acute respiratory distress syndrome and compared the two techniques. DESIGN AND
      SETTING: Prospective human study in a university hospital. PATIENTS: Fourteen
      mechanically ventilated patients with acute respiratory distress syndrome (nine
      primary; nine with intubation <7 days). INTERVENTIONS: All patients underwent a
      spiral CT of the thorax. We measured pulmonary thermal volume (PTV) and its
      components, extravascular lung water and pulmonary blood volume, with an
      integrated fiberoptic monitoring system (COLD Z-021). MEASUREMENTS AND RESULTS:
      PTV was tightly correlated with lung weight (LW) measured by CT (PTV = 0.6875 *
      LW(CT) + 292.77; correlation coefficient = 0.91; p < .0001; bias -11 +/- 8 %).
      Neither etiology of acute respiratory distress syndrome (primary vs. secondary)
      nor days of intubation affected the accuracy of thermal dye dilution in
      comparison with CT. There was no correlation between the extravascular lung water
      (12.3 +/- 3.4 mL/kg) and CT distribution of lung tissue compartments.
      Extravascular lung water and pulmonary blood volume showed good reproducibility
      in 32 pairs of thermal dye dilution measurements. CONCLUSIONS: Measurements of
      lung edema by thermal indocyanine green-dye double-dilution method show good
      correlation with those by quantitative computed tomography and good
      reproducibility in patients with acute respiratory distress syndrome.

PMID- 16276180
TI  - Facing the challenge: decreasing case fatality rates in severe sepsis despite
      increasing hospitalizations.
AB  - OBJECTIVE: To determine recent trends in severe sepsis-related rates of
      hospitalization, mortality, and hospital case fatality in a large geographic area
      and to determine the impact of age, race, and gender on these outcomes. DESIGN:
      Trend analysis for the period of 1995 to 2002. SETTING: Acute care hospitals in
      New Jersey. PATIENTS: Subjects > or = 18 yrs of age with severe sepsis who were
      hospitalized in New Jersey during the period of 1995 to 2002. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: We analyzed data from the 1995-2002 New
      Jersey State Inpatient Databases (SID) developed as part of the Healthcare Cost
      and Utilization Project (HCUP), covering all acute care hospitals in the state.
      On the basis of the International Classification of Diseases, Ninth Revision,
      Clinical Modification (ICD-9-CM) codes for septicemia and organ dysfunction, we
      identified 87,675 patients with severe sepsis. The percentage of patients with
      severe sepsis among all hospitalized patients with sepsis grew steadily, from
      32.7% to 44.7% (p < .0001), during these years. The crude rate of hospitalization
      with severe sepsis increased 54.2%, from 135.0/100,000 population in 1995 to
      208.2/100,000 population in 2002 (p < .0001). Over time, the crude mortality rate
      rose by 35.8% (p < .0001), whereas the crude case fatality rate (number of
      deaths/number of cases) fell from 51.0% to 45.0% (p < .0001). For any given year,
      the rates of hospitalization and mortality were greater among older patients.
      After adjustment by age, the rates among blacks were greater than among whites,
      and they were greater among males than females. At the same time, there was no
      significant difference in the age-adjusted hospital case fatality rates with
      regard to gender and race. There was a significant increase in age-adjusted
      gender- and race-specific rates for hospitalization and mortality from 1995 to
      2002. Blacks were more likely than whites to be admitted to the intensive care
      unit: for males, odds ratio = 1.19 (95% confidence interval, 1.13-1.26), and for
      females, odds ratio = 1.35 (95% confidence interval, 1.29-1.42). However,
      although case fatality rate was increased among patients admitted to the
      intensive care unit, this was not reflected in an increased case fatality among
      blacks. In addition, age-adjusted gender- and race-specific case fatality rates
      declined during 1995-2002. CONCLUSIONS: In spite of increasing rates of
      hospitalization and mortality, there is a decreasing case fatality rate for
      severe sepsis. These data suggest that advances in critical care practice before
      and during the study period have resulted in improved outcomes for this
      population.

PMID- 16276181
TI  - Heme oxygenase modulates small intestine leukocyte adhesion following hindlimb
      ischemia/reperfusion by regulating the expression of intercellular adhesion
      molecule-1.
AB  - OBJECTIVE: Heme oxygenase is the rate-limiting enzyme in the degradation of heme
      into carbon monoxide, iron, and bilirubin. Recent evidence suggests that the
      induction of heme oxygenase-1 is associated with potent anti-inflammatory
      properties. The objectives of this study were to determine the temporal,
      regional, and cellular distribution of heme oxygenase-1 within the small
      intestine and its role in modulating remote intestinal leukocyte recruitment
      following trauma induced by hindlimb ischemia/reperfusion. DESIGN: Randomized,
      controlled, prospective animal study. SETTING: Hospital surgical research
      laboratory. SUBJECTS: Male C57BL/6 mice. INTERVENTIONS: Mice underwent 1 hr of
      bilateral hindlimb ischemia, followed by 3, 6, 12, or 24 hrs of reperfusion.
      MEASUREMENTS AND MAIN RESULTS: Heme oxygenase-1 messenger RNA, heme oxygenase-1
      protein, and heme oxygenase activity were measured using reverse transcription
      polymerase chain reaction, Western blot, immunohistochemistry, and
      spectrophotometric assay, respectively. The jejunum was also exteriorized to
      quantify the flux of rolling and adherent leukocytes and R-Phycoerythrin
      conjugated intercellular adhesion molecule-1 monoclonal antibody fluorescence
      intensity in submucosal postcapillary venules with the use of intravital
      microscopy. Ischemia/reperfusion led to a significant increase in heme oxygenase
      1 messenger RNA in the jejunum and ileum 3 hrs following limb reperfusion, with a
      subsequent increase in heme oxygenase-1 protein and heme oxygenase activity at 6
      hrs. Ischemia/reperfusion also led to a significant 1.4-fold increase in
      leukocyte rolling, whereas inhibition of heme oxygenase via injection of tin
      protoporphyrin IX (20 micromol/kg intraperitoneally) resulted in a three-fold
      increase in leukocyte adhesion, compared with ischemia/reperfusion alone. This
      increase in adhesion was significantly reduced to baseline in mice treated with
      intercellular adhesion molecule-1 monoclonal antibody before heme oxygenase
      inhibition (40 microg/mouse), whereas inhibition of heme oxygenase activity
      following ischemia/reperfusion also led to a significant increase in R
      Phycoerythrin intercellular adhesion molecule-1 monoclonal antibody fluorescence
      intensity. CONCLUSIONS: Our data suggest that remote trauma induced by hindlimb
      ischemia/reperfusion leads to an increase in heme oxygenase activity within the
      small intestine, which modulates intercellular adhesion molecule-1 dependent
      intestinal leukocyte adhesion.

PMID- 16276182
TI  - Proapoptotic effect of curcumin on human neutrophils: activation of the p38
      mitogen-activated protein kinase pathway.
AB  - OBJECTIVE: Despite advances in the management of sepsis and acute respiratory
      distress syndrome, the mortality rate remains high. Delayed apoptosis of
      neutrophils is associated with multiple organ failure under those conditions.
      Thus, development of nontoxic neutrophil apoptosis regulating molecules may
      provide a novel therapeutic strategy. Curcumin is a promising dietary supplement
      for cancer prevention. However, the effect of curcumin on human neutrophil
      apoptosis remains unknown. We therefore hypothesized that curcumin would produce
      a proapoptotic effect on neutrophils. DESIGN: Prospective, controlled, and
      randomized in vitro study. SETTING: Research institute laboratory. SUBJECTS:
      Human peripheral neutrophils obtained from normal subjects. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: In the presence or absence of curcumin, both
      spontaneous neutrophil apoptosis and apoptosis of neutrophils following
      transmigration across a human lung endothelium-epithelium bilayer were studied by
      morphology and terminal dUTP nucleotide end labeling analyses, respectively.
      Myeloperoxidase activity and migration assays were performed to determine the
      impact of curcumin on neutrophil function. To elucidate the potential mechanism,
      the p38 mitogen-activated protein kinase pathway and caspase-3 activity were
      examined by Western blotting and enzymatic analyses. The data demonstrate that
      curcumin increased constitutive neutrophil apoptosis and abrogated the
      transbilayer migration-induced delay in neutrophil apoptosis. Neutrophil
      activation was reduced by curcumin treatment as evidenced by a decrease in
      migration and myeloperoxidase release. A marked increase in p38 phosphorylation
      and caspase-3 activity was observed following curcumin exposure. In addition,
      inhibition of p38 mitogen-activated protein kinase with SB203580 suppressed
      apoptosis and caspase-3 activation induced by curcumin. Thus, activation of p38
      mitogen-activated protein kinase or an increase in caspase-3 activity appears to
      contribute to the proapoptotic effect of human neutrophil apoptosis by curcumin.
      CONCLUSION: The characteristics of curcumin, including its proapoptotic effect
      and antidegranulation effect, make it a potential candidate for the therapy of
      neutrophil-induced lung injury and sepsis.

PMID- 16276183
TI  - Effects of different resuscitation fluids on tissue blood flow and oxidant injury
      in experimental rhabdomyolysis.
AB  - OBJECTIVE: This study was performed to evaluate the effects of 0.9% saline (SAL),
      0.9% saline + sodium bicarbonate + mannitol (SAL/BIC/MAN), and hypertonic saline
      dextran (HSD) on hemodynamic variables, tissue blood flow, and oxidant injuries
      in experimental traumatic rhabdomyolysis (TR) in rats subjected allogeneic muscle
      extract infusion. DESIGN: Prospective, randomized, experimental. SETTING:
      Physiology experiment laboratory. SUBJECTS: Male Sprague-Dawley rats, weighing
      250-300 g. INTERVENTIONS: All groups (n = 8 each) underwent femoral artery and
      vein catheterization. The animals in the TR, SAL, SAL/BIC/MAN, and HSD groups
      received an infusion of 2 mL of autologous muscle extract for 60 mins. After
      autologous muscle extract infusion, the SAL and HSD groups received 30 mL/kg 0.9%
      saline for 30 mins or 4 mL/kg HSD for 5 mins, respectively. The SAL/BIC/MAN group
      received 30 mL/kg 0.9% saline for 30 mins plus a bolus of 1 g/kg mannitol and a
      bolus of 2 mEq/kg sodium bicarbonate diluted in 1 mL of saline. At 2 hrs of
      autologous muscle extract infusion, erythrocyte flows in liver and kidney were
      measured by using a laser Doppler flowmeter. Then, blood samples and kidney and
      liver biopsies were taken to measure levels of glutathione and malondialdehyde.
      MEASUREMENTS AND MAIN RESULTS: TR caused decreases in mean arterial pressure,
      tissue blood flow, and tissue glutathione and an increase in malondialdehyde.
      Rats in the HSD group had significant metabolic acidosis. SAL resuscitation did
      not correct tissue blood flow and prevent oxidant injury. HSD increased tissue
      blood flow, mean arterial pressure, and liver and kidney glutathione and
      decreased serum, liver, and kidney malondialdehyde. SAL/BIC/MAN resuscitation
      corrected all oxidant damage variables but did not increase tissue blood flow.
      SAL/BIC/MAN preserved serum malondialdehyde and liver glutathione better than the
      HSD did. CONCLUSIONS: HSD prevented oxidant injury and restored tissue blood flow
      but increased metabolic acidosis that followed autologous muscle extract
      infusion. SAL/BIC/MAN seems to be more effective than HSD in decreasing oxidant
      injury. Further research on the effects of the solute overload and metabolic
      acidosis due to HSD resuscitation on renal function in experimental
      rhabdomyolysis is warranted.

PMID- 16276184
TI  - Effects of combined administration of vasopressin, epinephrine, and
      norepinephrine during cardiopulmonary resuscitation in pigs.
AB  - OBJECTIVE: Synergistic effects of epinephrine and vasopressin may be of benefit
      during cardiopulmonary resuscitation. However, cerebral perfusion was decreased
      when epinephrine was combined with vasopressin compared with vasopressin alone.
      Although a combined infusion of norepinephrine and vasopressin improves
      hemodynamic variables compared with norepinephrine alone during sepsis, it is
      unknown whether norepinephrine in addition to vasopressin and epinephrine changes
      vital organ perfusion during cardiopulmonary resuscitation. DESIGN: Prospective,
      randomized animal study. SETTING: : University hospital research laboratory.
      SUBJECTS: Twenty-one domestic pigs. INTERVENTIONS: After 4 mins of ventricular
      fibrillation and 3 mins of basic life support, the pigs were randomly assigned to
      receive either 200 microg/kg epinephrine, 0.4 units/kg vasopressin alone, or 45
      microg/kg norepinephrine plus 45 microg/kg epinephrine plus 0.4 units/kg
      vasopressin before defibrillation. MEASUREMENTS AND MAIN RESULTS: Organ perfusion
      was determined by radiolabeled microspheres. Myocardial blood flow (mean +/- sem)
      before and 90 secs and 5 mins after drug administration was 8 +/- 2, 25 +/- 6,
      and 7 +/- 1 mL/min/100 g after high-dose epinephrine, 12 +/- 1, 75 +/- 7, and 60
      +/- 10 mL/min/100 g after vasopressin, and 9 +/- 2, 95 +/- 26, and 46 +/- 15
      mL/min/100 g after vasopressin/epinephrine/norepinephrine, respectively (p < .05
      at 90 secs and 5 mins vasopressin vs. epinephrine and
      vasopressin/epinephrine/norepinephrine vs. epinephrine). At the same time points,
      cerebral blood flow was 8 +/- 2, 23 +/- 3, and 17 +/- 3 mL/min/100 g after
      epinephrine, 11 +/- 3, 55 +/- 7, and 52 +/- 7 mL/min/100 g after vasopressin, and
      11 +/- 4, 67 +/- 13, and 53 +/- 12 mL/min/100 g after
      vasopressin/epinephrine/norepinephrine, respectively (p < .05 at 90 secs and 5
      mins vasopressin vs. epinephrine and vasopressin/epinephrine/norepinephrine vs.
      epinephrine). Two of seven animals in the epinephrine group, four of seven
      animals in the vasopressin/epinephrine/norepinephrine group, and seven of seven
      animals in the vasopressin group could be successfully resuscitated (p < .05
      vasopressin vs. epinephrine). CONCLUSIONS: Vasopressin with or without
      epinephrine and norepinephrine resulted in higher myocardial and cerebral
      perfusion than epinephrine alone, but there was no benefit in adding
      norepinephrine to vasopressin and epinephrine with regard to cardiac and cerebral
      blood flow during cardiopulmonary resuscitation.

PMID- 16276185
TI  - Amiloride combined with small-volume resuscitation with hypertonic saline is
      superior in ameliorating trauma-hemorrhagic shock-induced lung injury in rats to
      the administration of either agent alone.
AB  - OBJECTIVE: Recognition of the limitations of standard crystalloid resuscitation
      has led to exploration for alternative resuscitation strategies that might better
      prevent the development of trauma-hemorrhage-induced organ dysfunction and
      systemic inflammation. Thus, the goal of this study was to compare the effects of
      two resuscitation strategies alone and in combination with that of standard
      resuscitation with Ringer's lactate. These two strategies were intravenous
      injection of amiloride, an inhibitor of Na/H exchange and epithelial Na channels,
      and resuscitation with hypertonic saline. DESIGN: Prospective animal study with
      concurrent control. SETTING: Small animal laboratory. SUBJECTS: Adult male
      Sprague-Dawley rats. INTERVENTIONS: Rats injected with amiloride or its vehicle
      were subjected to trauma-hemorrhagic shock (T/HS) or trauma sham-shock (T/SS) and
      resuscitated with Ringer's lactate or hypertonic saline. The T/HS model consisted
      of a laparotomy plus 90 mins of shock (mean arterial pressure 30 mm Hg). Three
      hours after the end of the shock or sham-shock period, lung permeability, lung
      histology, pulmonary neutrophil sequestration, neutrophil CD11b expression, gut
      injury, and red blood cell rigidification were assessed. MEASUREMENTS AND MAIN
      RESULTS: Both amiloride and hypertonic saline reduced T/HS-induced pulmonary
      permeability and neutrophil sequestration, and coadministration of these two
      agents was more efficacious than administration of the individual agents. In
      contrast, whereas gut injury was attenuated by both amiloride and hypertonic
      saline, combined administration of amiloride and hypertonic saline failed to
      further protect the gut. Additionally, hypertonic saline reduced both neutrophil
      CD11b expression and red blood cell rigidification, whereas amiloride was without
      effect. CONCLUSIONS: Combined administration of amiloride and small-volume
      resuscitation with hypertonic saline may be a strategy worthy of further
      evaluation in the therapy of shock-induced distant organ injury.

PMID- 16276186
TI  - Cariporide minimizes adverse myocardial effects of epinephrine during
      resuscitation from ventricular fibrillation.
AB  - OBJECTIVE: Epinephrine given during closed-chest resuscitation increases blood
      flow across the coronary and cerebral circuits. However, epinephrine worsens
      reperfusion arrhythmias and intensifies postresuscitation myocardial dysfunction.
      We investigated whether cariporide-a selective sodium-hydrogen exchanger isoform
      1 inhibitor-could ameliorate such adverse effects without diminishing its
      vasopressor actions. DESIGN: Randomized animal study. SETTING: University-based
      animal laboratory. SUBJECTS: Twenty-four anesthetized male domestic pigs (29-43
      kg). INTERVENTIONS: Ventricular fibrillation was electrically induced and left
      untreated for 8 mins. Pigs were randomized to receive after 2 mins of chest
      compression a 3 mg/kg bolus of cariporide (n = 8), a 0.02 mg/kg bolus of
      epinephrine (n = 8), or a combination of cariporide and epinephrine (n = 8).
      Additional doses of epinephrine were given if the coronary perfusion pressure
      decreased below 15 mm Hg. Successfully resuscitated pigs were observed for 72
      hrs. MEASUREMENTS AND MAIN RESULTS: The averaged coronary perfusion pressure was
      higher in the epinephrine (34 +/- 11 mm Hg, p = .001) and cariporide/epinephrine
      (35 +/- 10 mm Hg, p < .001) groups compared with the cariporide group (15 +/- 6
      mm Hg). All pigs in the epinephrine and cariporide/epinephrine groups but only
      six in the cariporide group were successfully resuscitated and survived 72 hrs.
      During the immediate postresuscitation period, four of eight pigs in the
      epinephrine group had episodes of recurrent ventricular fibrillation or pulseless
      ventricular tachycardia requiring additional electrical shocks (7.0 +/- 6.4) but
      none in the cariporide and cariporide/epinephrine groups (chi-square, p = .008).
      Myocardial dysfunction occurred early after return of spontaneous circulation but
      only in the epinephrine group. CONCLUSIONS: The combined administration of
      cariporide and epinephrine prompted adequate pressor effects during chest
      compression and facilitated reestablishment of cardiac activity without episodes
      of recurrent ventricular fibrillation or transient myocardial dysfunction as with
      epinephrine alone.

PMID- 16276187
TI  - Hypercapnic acidosis does not modulate the severity of bacterial pneumonia
      induced lung injury.
AB  - OBJECTIVE: Deliberate induction of hypercapnic acidosis protects against lung
      injury after ischemia-reperfusion, endotoxin-induced, and ventilation-induced
      lung injury. The efficacy of hypercapnic acidosis in bacterial lung infection, a
      common cause of acute respiratory distress syndrome, is not known. Furthermore,
      its effect may differ depending on the presence or absence of antibiotic therapy.
      We investigated whether hypercapnic acidosis-induced by adding CO2 to inspired
      gas-would protect against acute lung injury induced by pulmonary Escherichia coli
      instillation in an in vivo model in the presence and absence of effective
      antibiotic therapy. DESIGN: Prospective randomized animal study. SETTING:
      University research laboratory. SUBJECTS: Adult male Wistar-Kyoto rats.
      INTERVENTIONS: The animals were anesthetized and ventilated. In series 1, rats
      were administered intravenous ceftriaxone (100 mg x kg) and randomized to
      normocapnia (Normocapnia-ABx; Fico2 0.00, n = 10) or hypercapnia (Hypercapnia
      ABx; Fico2 0.05, n = 10) groups. E. coli (8.4 x 10 colony forming units) was
      instilled intratracheally. Series 2 animals did not receive antibiotics. They
      were randomized to normocapnia (Normocapnia, n = 10) or hypercapnia (Hypercapnia,
      n = 10) groups, and intratracheal E. coli was administered. All animals were
      ventilated for 6 hrs. MEASUREMENTS AND MAIN RESULTS: In series 1, there were no
      differences between Hypercapnia-ABx and Normocapnia-ABx groups with regard to: (a
      a)o2 gradient (mean +/- sem; 215 +/- 13 vs. 252 +/- 22 mm Hg), Pao2,
      bronchoalveolar lavage neutrophil count, static lung compliance, or histologic
      injury. Lung bacterial yield was not different between the groups. In series 2,
      in the absence of antibiotic therapy, there were no differences between
      Hypercapnia and Normocapnia groups in: (a-a)o2 gradient (mean +/- sem, 345 +/- 25
      vs. 332 +/- 23 mm Hg), systemic Pao2, bronchoalveolar lavage neutrophil count, or
      static lung compliance. Lung bacterial yield was not altered by hypercapnia in
      either series 1 or 2. CONCLUSIONS: We conclude that hypercapnic acidosis did not
      alter the magnitude of the lung injury induced by intratracheal E. coli
      instillation in the presence or absence of antibiotics.

PMID- 16276188
TI  - Marked synergism between vasopressin and angiotensin II in a human isolated
      artery.
AB  - OBJECTIVE: To determine the direct contractile effects of angiotensin II (AII)
      and vasopressin (VP), and the effects of combinations of these agonists, in human
      isolated gastroepiploic arteries in vitro. DESIGN: Laboratory and clinical
      investigation. SETTING: University laboratory and hospital. SUBJECTS: Ring
      segments were prepared from gastroepiploic arteries obtained from 57 patients
      undergoing gastrectomy. Blood samples were obtained from ten patients after
      severe hemorrhage and from five healthy volunteers. INTERVENTIONS: Mechanical
      activity in the rings was assessed using a strain gauge. Plasma concentrations of
      AII and VP in the blood samples were measured using radioimmunoassay kits.
      MEASUREMENTS AND MAIN RESULTS: Both AII (1 or 10 ng/mL) and VP (100 or 500 pg/mL)
      produced concentration-dependent contractions in the rings. However, whereas VP
      produced reproducible sustained contractions, the contractile responses induced
      by multiple applications of AII showed marked desensitization (i.e.,
      tachyphylaxis). Indeed, by the sixth application of either 1 ng/mL AII or 10
      ng/mL AII, the contractile responses were <20% of the initial (control) response.
      During applications of AII after the sixth, the co-application of a low
      concentration of VP (100 pg/mL) fully restored the contractile response to AII in
      a clearly more-than-additive fashion. Similarly, the tachyphylaxis seen on AII
      application alone did not occur with repeated applications of an AII +
      norepinephrine mixture. In patients who had experienced hemorrhage, there were
      marked elevations of both AII and VP plasma concentrations, with values as high
      as 2.2 ng/mL and 550 pg/mL, respectively. CONCLUSION: These results indicate that
      there is a powerful synergism between the contractile effects of low-dose VP and
      AII in this human isolated artery. Moreover, the elevations of plasma AII and VP
      levels during hemorrhage suggest that this synergism may be both physiologically
      and clinically important in optimizing vasoconstriction and maintaining blood
      pressure in such critical states.

PMID- 16276190
TI  - Cannabinoid antagonist AM 281 reduces mortality rate and neurologic dysfunction
      after cecal ligation and puncture in rats.
AB  - OBJECTIVES: The purpose of this study was to examine whether anandamide, an
      endogenous cannabinoid receptor ligand, is involved in the pathogenesis of septic
      encephalopathy. DESIGN: Prospective, controlled study. SUBJECTS: Male Wistar rats
      (7 wks old) were randomly divided into four groups as follows: group 1, control
      (0.5 mL of saline injected subcutaneously); group 2, sham (surgical abdominal
      incision and suturing were performed, but ligation and puncture of the cecum were
      omitted); group 3, cecal ligation and puncture (CLP); group 4, CLP + AM 281 ([N
      morpholin-4-yl]-5-[2,4-yl]-5-[2,4-dichlorophenyl]-4-methyl-1H-pyrazole-3
      carboxamide) as the cannabinoid receptor antagonist (1 mg/kg intraperitoneally).
      INTERVENTIONS: Sepsis was induced by CLP under pentobarbital anesthesia (10 mg/kg
      intraperitoneally) with 1% isoflurane. A 2-Fr high-fidelity micromanometer
      catheter was inserted into the left ventricle via the right carotid artery to
      assess hemodynamics. Each of the rats was neurologically assessed at 30 mins and
      12, 24, and 48 hrs after the treatment. The cytoplasmic levels of caspase-3 in
      the hippocampi were assayed before surgery and at 30 mins and 24 and 48 hrs after
      surgery using Western blotting techniques. To examine the effects of AM 281 on
      neurologic function and mortality rate, we set another control group treated
      solely with AM 281. Selective inducible nitric oxide synthase inhibitor, L-N6-(1
      iminoethyl)-lysine (4 mg/kg), was injected intraperitoneally immediately after
      CLP to produce the CLP + L-N6-(1-iminoethyl)-lysine group to exclude the
      influence of depressed hemodynamics on neurologic impairment. MEASUREMENTS AND
      MAIN RESULTS: It was found that administration of AM 281 could prevent the
      hemodynamic changes induced by sepsis. Reflex responses, including the pinna,
      corneal, paw or tail flexion, and righting reflexes, and the escape response
      significantly decreased in the CLP and CLP + L-N6-(1-iminoethyl)-lysine groups at
      48 hrs after the surgery. In contrast, no changes in these reflex responses were
      found between the CLP + AM 281 and control and sham groups. In addition, no
      effects of the administration of AM 281 on neurologic function and mortality rate
      in the control group were found. Tissue caspase-3 levels were elevated at 48 hrs
      after CLP in the CLP alone group (means +/- sd: control, 3.9 +/- 0.4; sham, 4.2
      +/- 0.4; CLP, 7.1 +/- 1.0 [p < .01]; CLP + AM 281, 4.0 +/- 0.5 densitometric
      units). In addition, administration of AM 281 also decreased the mortality rate
      (p < .05). CONCLUSIONS: Administration of AM 281 prevented the hemodynamic
      changes and development of neurologic dysfunction occurring in association with
      septic shock, and could decrease the mortality rate in experimentally induced
      septic shock in rats. Although further studies are necessary to determine whether
      endogenous cannabinoids cause septic encephalopathy in rats directly or via their
      effects on systemic hemodynamics, the beneficial effects of AM 281 on these rats
      might have significant therapeutic implications in cases of septic
      encephalopathy.

PMID- 16276189
TI  - Activation of an efferent cholinergic pathway produces strong protection against
      myocardial ischemia/reperfusion injury in rats.
AB  - OBJECTIVE: A vagus nerve-mediated, brain cholinergic protective mechanism
      activated by melanocortin peptides is operative in conditions of circulatory
      shock; moreover, there is anatomical evidence of dual vagal-cardiac efferent
      pathways in rats, which could play different roles in controlling heart function.
      Therefore, we investigated the role and functional mechanism of such vagal
      efferent pathway(s) in an experimental model of ischemic heart disease. DESIGN:
      Randomized experimental study. SETTING: Research laboratory. SUBJECTS: Adult
      Wistar rats of either sex. INTERVENTIONS: After bilateral cervical vagotomy (with
      or without pretreatment with atropine), efferent vagal fibers were electrically
      stimulated in rats subjected to coronary artery occlusion (5 mins) followed by
      reperfusion (5 mins). Other rats (intact, vagotomized, or pretreated with
      atropine) were treated with nanomolar doses of melanocortin peptides.
      MEASUREMENTS AND MAIN RESULTS: Electrical stimulation of efferent vagal fibers (5
      V, 2 m secs, 1-9 Hz, for the whole period of ischemia/reperfusion) strongly
      reduced the high incidence of severe arrhythmias and lethality, reduced the
      increase in free radical blood levels and left-ventricle histologic alterations,
      and augmented the extracellular signal-regulated kinase activation. Treatment
      with the melanocortin peptides adrenocorticotropin and gamma2-melanocyte
      stimulating hormone (162 nmol/kg intravenously or 16.2 nmol/kg
      intracerebroventricularly, during coronary occlusion) produced the same
      protective effects of electrical stimulation and with the same muscarinic
      acetylcholine receptor-dependent mechanism, seemingly through brain activation
      (mediated by melanocortin MC3 receptors, as previously described) of such
      efferent vagal pathway. CONCLUSIONS: The present results give evidence for the
      identification of a protective, melanocortin-activated, efferent vagal
      cholinergic pathway, operative in conditions of myocardial ischemia/reperfusion.
      These data suggest that melanocortins and pertinent compounds able to activate
      such a pathway could provide the potential for development of a new class of
      drugs for a novel approach to management of ischemic heart disease.

PMID- 16276191
TI  - Determinants of red blood cell transfusions in a pediatric critical care unit: a
      prospective, descriptive epidemiological study.
AB  - OBJECTIVE: To determine the incidence and to characterize the determinants of red
      blood cell transfusions in critically ill children. DESIGN: Prospective,
      descriptive epidemiologic study. SETTING: A single-center, multidisciplinary,
      tertiary care level, university-affiliated, pediatric intensive care unit (PICU).
      PATIENTS: Critically ill children. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Of 1,047 consecutive admissions over a 1-yr period, 985 were retained
      for study. At least one transfusion was given in 139 cases (14%). Incidence rate
      of transfusion was 304 transfusions/1,000 cases. Possible determinants of red
      blood cell transfusions were identified and prospectively monitored during PICU
      stay until a first transfusion event (transfused cases) or up until the time of
      death or discharge from PICU (nontransfused cases). Four significant determinants
      of a first red blood cell transfusion event were retained in the multivariate
      analysis (odds ratio, 95% confidence interval, p): a hemoglobin level <9.5 g/dL
      during PICU stay (13.26, 8.04-21.88, p < .001), an admission diagnosis of cardiac
      disease (8.07, 5.14-14.65, p < .001), an admission Pediatric Risk of Mortality
      score >10 (4.83, 2.33-10.04, p < .001), and the presence of multiple organ
      dysfunction syndrome during the stay (2.06, 1.18-3.57, p = .01). CONCLUSION: A
      significant proportion of critically ill children receive at least one red blood
      cell transfusion during their PICU stay. Presence of anemia, cardiac disease,
      severe critical illness, and multiple organ dysfunction syndrome are the most
      significant determinants of red blood cell transfusions in PICU.

PMID- 16276193
TI  - Noninvasive positive pressure ventilation in the intensive care unit: a concise
      review.
AB  - OBJECTIVE: To critically assess available high-level clinical studies regarding
      use of noninvasive positive pressure ventilation in varied intensive care unit
      settings. DATA SOURCE: Search of pertinent articles within Ovid MEDLINE from 1975
      to 2005, CINAHL from 1982 to 2005, EMBASE from 1988 to 2005, and Web of Science
      from 1993 to 2005. STUDY SELECTION: Randomized, controlled clinical trials and
      cohort studies and observational studies the authors consider important or novel.
      DATA EXTRACTION/SYNTHESIS: Performed equally by both authors with the use of an
      Excel data spreadsheet. CONCLUSION: There is abundant level I evidence supporting
      the use of noninvasive positive pressure ventilation in such critical care
      settings as acute hypercapnic respiratory failure, particularly related to
      chronic obstructive pulmonary disease, and acute cardiogenic pulmonary edema. We
      also report on other clinical scenarios in which the data may be somewhat less
      compelling, but evidence favors a noninvasive positive pressure ventilation
      trial. Some well designed studies suggest that noninvasive positive pressure
      ventilation is not an appropriate intervention for patients who have failed
      endotracheal extubation.

PMID- 16276192
TI  - Influence of definition and location of hypotension on outcome following severe
      pediatric traumatic brain injury.
AB  - OBJECTIVE: To examine the influence of definition and location (field, emergency
      department, or pediatric intensive care unit) of hypotension on outcome following
      severe pediatric traumatic brain injury. DESIGN: Retrospective cohort study.
      SETTING: Harborview Medical Center (level I pediatric trauma center), Seattle,
      WA, over a 5-yr period between 1998 and 2003. PATIENTS: Ninety-three children <14
      yrs of age with traumatic brain injury following injury, head Abbreviated Injury
      Score > or = 3, and pediatric intensive care unit admission Glasgow Coma Scale
      score <9 formed the analytic sample. Data sources included the Harborview Trauma
      Registry and hospital records. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: The relationship between hypotension and outcome was examined comparing
      two definitions of hypotension: a) systolic blood pressure <5th percentile for
      age; and b) systolic blood pressure <90 mm Hg. Hospital discharge Glasgow Outcome
      Score <4 or disposition of either death or discharge to a skilled nursing
      facility was considered a poor outcome. Pediatric intensive care unit and
      hospital length of stay were also examined. Systolic blood pressure <5th
      percentile for age was more highly associated with poor hospital discharge
      Glasgow Outcome Score (p = .001), poor disposition (p = .02), pediatric intensive
      care unit length of stay (rate ratio 9.5; 95% confidence interval 6.7-12.3), and
      hospital length of stay (rate ratio 18.8; 95% confidence interval 14.0-23.5) than
      systolic blood pressure <90 mm Hg. Hypotension occurring in either the field or
      emergency department, but not in the pediatric intensive care unit, was
      associated with poor Glasgow Outcome Score (p = .008), poor disposition (p =
      .03), and hospital length of stay (rate ratio 18.7; 95% confidence interval 13.1
      24.2). CONCLUSIONS: Early hypotension, defined as systolic blood pressure <5th
      percentile for age in the field and/or emergency department, was a better
      predictor of poor outcome than delayed hypotension or the use of systolic blood
      pressure <90 mm Hg.

PMID- 16276194
TI  - Arginine vasopressin in 316 patients with advanced vasodilatory shock.
AB  - OBJECTIVE: To assess the effects of arginine vasopressin (AVP) on hemodynamic,
      clinical, and laboratory variables and to determine its adverse side effects in
      advanced vasodilatory shock. DESIGN: Retrospective study. PATIENTS: A total of
      316 patients. INTERVENTIONS: AVP infusion (4 units/hr). MEASUREMENTS AND MAIN
      RESULTS: Cardiocirculatory, laboratory, and clinical variables were evaluated
      before, 0.5, 1, 4, 12, 24, 48, and 72 hrs after administration of AVP. AVP
      increased mean arterial pressure, systemic vascular resistance, and stroke volume
      index. Heart rate, central venous pressure, mean pulmonary arterial pressure,
      norepinephrine, milrinone, and epinephrine requirements decreased. There was no
      difference in the hemodynamic response between patients with septic shock,
      postcardiotomy shock, or systemic inflammatory response syndrome. Cardiac index
      decreased in 41.1% of patients during AVP treatment. In patients with
      hyperdynamic circulation before AVP, cardiac index decreased, whereas it remained
      uncharged or tended to increase in patients with normodynamic or hypodynamic
      circulation. During the course of AVP treatment, liver enzymes (28.5% of
      patients) and total bilirubin concentrations (69.3% of patients) increased,
      whereas platelet count decreased (73.4% of patients). Simultaneous hemofiltration
      significantly contributed to the decrease in platelet count (p < .001) and
      increase in bilirubin (p < .001). Whereas patients with an increase in bilirubin
      were more likely to die, a decrease in cardiac index or platelet count and an
      increase in liver enzymes did not affect mortality. Systemic inflammatory
      response syndrome as admission diagnosis, a high degree of multiple organ
      dysfunction, and norepinephrine requirements of >0.5 microg x kg x min before AVP
      treatment were independent risk factors for death from advanced vasodilatory
      shock treated with AVP. If norepinephrine dosages exceeded 0.6 microg x kg x min
      before AVP treatment, a substantial increase in mortality occurred. CONCLUSIONS:
      Supplementary AVP infusion improved cardiocirculatory function in advanced
      vasodilatory shock, but an increase in liver enzymes and bilirubin, and a
      decrease in platelet count occurred during AVP therapy, particularly during
      simultaneous hemofiltration. Initiation of AVP infusion before norepinephrine
      requirements exceeding 0.6 microg x kg x min may improve outcome.

PMID- 16276195
TI  - Fresh frozen plasma transfusion in critically ill medical patients with
      coagulopathy.
AB  - OBJECTIVE: Although restrictive red cell transfusion practice has become a
      standard of care in the critically ill, data on the use of fresh frozen plasma
      (FFP) are limited. We hypothesized that the practice of FFP transfusion in the
      medical intensive care unit is variable and that liberal use may not be
      associated with improved outcome. DESIGN: Retrospective cohort study. SETTING: A
      24-bed medical intensive care unit in a tertiary referral center. PATIENTS: All
      patients admitted to a medical intensive care unit during a 5-month period who
      had abnormal coagulation defined as international normalized ratio (INR) of > or
      = 1.5-times normal. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We
      collected data on demographics, severity of illness as measured by Acute
      Physiology and Chronic Health Evaluation (APACHE) III scores, INR, bleeding
      episodes, and transfusion complications. We identified 115 patients with
      coagulopathy (INR of > or = 1.5) but without active bleeding. A total of 44
      patients (38.3%) received FFP transfusion. INR was corrected in 16 of 44 patients
      (36%) who received transfusion. Median dose of FFP was 17 mL/kg in patients who
      had INR corrected vs. 10 mL/kg in those who did not (p = .018). There was no
      difference in age, sex, APACHE III scores, liver disease, Coumadin treatment, or
      INR level between those who did and did not receive FFP. Invasive procedures
      (68.2% vs. 40.8%, p = .004) and history of recent gastrointestinal bleeding (41%
      vs. 7%, p < .001) were more frequent in the group with transfusion. Although
      there was no difference in new bleeding episodes (6.8% in transfused vs. 2.8% in
      nontransfused group, p = .369), new onset acute lung injury was more frequent in
      the transfused group (18% vs. 4%, p = .021). Adjusted for severity of illness,
      hospital mortality and intensive care unit length of stay among survivors were
      not different between the two groups. CONCLUSION: The risk-benefit ratio of FFP
      transfusion in critically ill medical patients with coagulopathy may not be
      favorable. Randomized controlled trials evaluating restrictive vs. liberal FFP
      transfusion strategies are warranted.

PMID- 16276196
TI  - Preoxygenation in critically ill patients requiring emergency tracheal
      intubation.
AB  - OBJECTIVE: To determine the effectiveness of preoxygenation with 100% oxygen in
      the critically ill patient in preparation for emergency tracheal intubation.
      DESIGN: Nonrandomized, controlled trial. SETTING: Large, level 1 trauma center,
      tertiary care intensive care unit. PATIENTS: Critically ill patients failing
      noninvasive respiratory support techniques who require tracheal intubation
      followed by mechanical ventilation. INTERVENTIONS: A baseline arterial blood gas
      was obtained on noninvasive therapy and 4 mins post-100% oxygen therapy with a
      bag-mask assembly. Best effort to achieve a tight-fitting mask seal was pursued
      coupled with other mask ventilation maneuvers to optimize noninvasive oxygenation
      and ventilation. MEASUREMENTS AND MAIN RESULTS: A total of 42 patients
      consecutively intubated during the 15-month study period were studied. The
      baseline Pao2 (mean +/- sd) with concurrent noninvasive support was 67 +/- 19.6
      mm Hg (range, 43-88 mm Hg) and increased a mean of 37 mm Hg to 103.8 +/- 63.2 mm
      Hg after 4 mins of preoxygenation with 100% oxygen. A total of 36% of patients
      had minimal changes (+/-5%) in their baseline Pao2, and only 19% increased their
      baseline Pao2 by at least 50 mm Hg after preoxygenation maneuvers. CONCLUSIONS:
      The critically ill patient has little reserve to tolerate interruption of oxygen
      delivery and, thus, is at risk for hypoxemia during emergency airway management.
      Preoxygenation efforts as described in this clinical trial appear to be
      marginally effective in regard to providing a reasonable safeguard against
      hypoxemia during laryngoscopy and endotracheal intubation.

PMID- 16276197
TI  - Lung isolation in a child with unilateral necrotizing Clostridium perfringens
      pneumonia.
AB  - OBJECTIVE: To describe lung isolation and the selective application of continuous
      positive airway pressure using an endobronchial blocker in a patient with sickle
      cell disease and unilateral necrotizing Clostridium perfringens pneumonia.
      DESIGN: Case report. SETTING: Pediatric intensive care unit. PATIENT: A 12-yr-old
      male with sickle cell disease developed persistent necrotizing pneumonia of the
      left lung following exchange transfusion for acute chest syndrome and hyper
      hemolytic syndrome. INTERVENTIONS: An endobronchial blocker was placed into the
      left main stem bronchus for lung isolation and application of continuous positive
      airway pressure to the left lung for 48 hrs. MEASUREMENTS AND MAIN RESULTS: After
      14 days of persistent atelectasis of the left lung despite thorascopic
      decortication and multiple bronchoscopies, our patient had substantial lung
      aeration within 48 hrs of continuous positive airway pressure applied via the
      endobronchial blocker. Lung resection was avoided and the patient was
      successfully extubated 2 days after removal of the blocker. CONCLUSIONS: This
      case report demonstrates a therapeutic application of prolonged lung isolation
      and differential ventilation in a patient with an airway too small for
      commercially available double-lumen endotracheal tubes. The apparent success of
      this intervention suggests the feasibility of selective ventilation in pediatric
      patients and highlights a novel application of the bronchial blocker.

PMID- 16276198
TI  - Prophylactic fenoldopam for renal protection? No, thank you, not for me--not yet
      at least.

PMID- 16276199
TI  - Hydrocortisone in septic shock: too much, too little, too soon?

PMID- 16276200
TI  - Noninvasive ventilation for postextubation respiratory failure: perhaps not to
      treat but at least to prevent!

PMID- 16276201
TI  - Prevention of ventilator-associated pneumonia: "Freeze, don't move!".

PMID- 16276202
TI  - Low-dose adrenocorticotropic hormone test is not ready for routine adrenal
      function testing in the intensive care unit.

PMID- 16276203
TI  - Consideration before administering cytotoxic chemotherapy to the critically ill.

PMID- 16276204
TI  - The Holy Grail of shock resuscitation.

PMID- 16276205
TI  - Glutamine: a double edge sword in the intensive care unit?

PMID- 16276206
TI  - Tracheostomy for ventilated patients--not when, but in whom?

PMID- 16276207
TI  - Apolipoprotein E: from Alzheimer's to sepsis.

PMID- 16276208
TI  - Galileo and the discovery of truth: Why does tracheostomy reduce sedation and
      analgesia requirements?

PMID- 16276209
TI  - Lung water measurements: Are we there yet?

PMID- 16276210
TI  - Sepsis: the changing times.

PMID- 16276211
TI  - Heme oxygenase-1: a pluripotent sentinel limiting the systemic inflammatory
      response to extremity ischemia and reperfusion.

PMID- 16276212
TI  - An old spice with new twists: curcumin, p38 mitogen-activated protein kinase, and
      apoptosis.

PMID- 16276213
TI  - Combining arginine-vasopressin with catecholamines during cardiopulmonary
      resuscitation: mirror, mirror, on the wall, is there a best mixture at all?

PMID- 16276214
TI  - Cariporide in cardiac resuscitation--Does it really make a difference?

PMID- 16276215
TI  - Neurocardiology: antifibrillatory effects of heart-brain interactions after
      myocardial reperfusion.

PMID- 16276216
TI  - What hemoglobin value should one use in transfusing a critically ill child?

PMID- 16276217
TI  - So hypotension is common: but what are the best treatment goals for kids with
      severe traumatic brain injury?

PMID- 16276218
TI  - Vasopressin: A tool as rescue therapy? Take care of dosages and adverse effects!

PMID- 16276219
TI  - Fresh frozen plasma: friend or faux pas in critical illness?

PMID- 16276220
TI  - Making tracheal intubation safer in the critically ill patient.

PMID- 16276222
TI  - Need for critical appraisal of implementation of use of lower tidal volumes.

PMID- 16276224
TI  - Hyperglycemia enhances the cytokine production and oxidative responses to a low
      but not high dose of endotoxin in rats.

PMID- 16276226
TI  - Quantitative real-time polymerase chain reaction for detection of bacteria:
      wanted, dead or alive?

PMID- 16276227
TI  - Cerebral output of cytokines in patients with pneumococcal meningitis.

PMID- 16276229
TI  - Critical illness neuromuscular abnormalities in patients with acute respiratory
      distress syndrome.

PMID- 16276231
TI  - Sedation in traumatic brain injury: avoid etomidate.

PMID- 16276235
TI  - Statin therapy for prevention and treatment of acute and chronic cardiovascular
      disease: update on recent trials and metaanalyses.
AB  - PURPOSE OF REVIEW: To summarize the evidence from recent clinical trials and
      metaanalyses on the efficacy of statin therapy to reduce death, myocardial
      infarction and stroke, and to review the effects of statins in patients with low
      LDL cholesterol, diabetes, end-stage renal disease, and acute coronary syndrome.
      RECENT FINDINGS: In large metaanalyses of randomized controlled trials relative
      risk reductions from statins compared with placebo for patients with manifest or
      with risk factors for coronary artery disease were 13% for overall mortality, 26%
      for fatal and nonfatal myocardial infarction, and 18% for fatal and nonfatal
      stroke. Evidence from large trials suggests that patients with type II diabetes
      compared with patients without diabetes have similar risk reductions from statins
      for cardiovascular events, but this benefit is not seen in patients with diabetes
      and end-stage renal disease. In patients with acute coronary syndrome, early
      treatment with high-dose atorvastatin reduces cardiovascular morbidity after the
      first 4 months following the event, but the impact on mortality endpoints remains
      less clear. Results from recent trials in patients with stable coronary artery
      disease or type II diabetes suggest that statins provide benefit at considerable
      low LDL cholesterol levels. Therefore, target values for LDL cholesterol of less
      than 1.8 mmol/l (<70 mg/dl) should be considered for all patients with coronary
      artery disease or equivalent coronary risk. SUMMARY: For patients at high risk of
      coronary artery disease there is growing evidence for the concept of 'the lower,
      the better' regarding LDL cholesterol levels. Ongoing trials are further
      investigating the safety of lower target values in patients at various risk of
      coronary artery disease.

PMID- 16276236
TI  - Statin pharmacogenomics: what have we learned, and what remains unanswered?
AB  - PURPOSE OF REVIEW: Statins are widely prescribed and are established as first
      line therapy for the primary and secondary prevention of coronary heart disease.
      Response to treatment varies considerably from person to person; however,
      inherited traits (genetic variability) may play a central role in this inter
      individual variation. The purpose of this review is to summarize recent progress
      in the research for exploring genetic determinants of clinical efficacy and
      safety of statin therapy. RECENT FINDINGS: In addition to 41 previous studies of
      19 genes, the results of 17 pharmacogenomic studies investigating the
      relationship between common genetic variants and response to statin therapy in
      terms of lipid responses, clinical outcomes, and adverse events have been
      reported since January 2004 - 15 candidate genes related to pharmacodynamics and
      three to pharmacokinetics of statins. These reported data suggest that genetic
      variations influencing intestinal cholesterol absorption, cholesterol production,
      and lipoprotein catabolism may all play a role in modulating responsiveness, as
      well as genes involved in drug metabolism of statins. They also suggest that
      combined analysis of multiple variants in several genes, all of which have
      possible functional relations, is more likely to give significant results,
      especially when being performed with a larger number of participants. SUMMARY:
      Pharmacogenomic studies of statin therapy will provide a better picture as to who
      is most likely and least likely to benefit from treatment, which results in more
      individualized management of coronary artery disease.

PMID- 16276237
TI  - Effect of statins in stroke prevention.
AB  - PURPOSE OF REVIEW: This paper reviews recent studies into the outcomes of
      clinical trials in which statin therapy has been used in the prevention and
      treatment of strokes. RECENT DEVELOPMENTS: Epidemiologic studies found no or
      little association between blood cholesterol levels and stroke. Randomized trials
      have confirmed that LDL lowering decreased the risk of stroke, in diabetic or
      hypertensive patients with 'normal' LDL cholesterol at baseline, and in patients
      with coronary artery disease, with respectively 48, 27 and 25% reduction in
      stroke incidence. A meta-analysis of trials showed that the greater the LDL
      cholesterol reduction, the greater the intima-media thickness and stroke risk
      reductions. Even if statins also have 'pleiotropic' effects, their main action
      seems to be through LDL reduction. The Heart Protection Study only included
      strokes that occurred 4.6 years before--a time when the stroke event rate is low
      and the cardiac event rate is high, and so may not have had the power to find a
      true effect of LDL cholesterol lowering in preventing recurrent stroke. The
      Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial
      may give a definite answer because SPARCL investigators included 4732 patients
      with brain infarction or transient ischemic attacks and no history of myocardial
      infarction within 6 months of their stroke event, at a time when the expected
      stroke rate is very high and the myocardial infarction rate is very low. The
      results should be announced by mid-2006. SUMMARY: The positive effect of statins
      on stroke observed in trials of patients with coronary heart disease depended
      mainly on between-group LDL reduction, but other mechanisms could be involved.
      Though effective in prevention of major coronary events after a first stroke,
      statins have not yet been proven effective in prevention of recurrent stroke.

PMID- 16276238
TI  - Can statin therapy really reduce the risk of Alzheimer's disease and slow its
      progression?
AB  - PURPOSE OF REVIEW: Statins are the most used cholesterol-lowering agents
      worldwide. Earlier studies suggested that they may have preventive effects in
      Alzheimer's disease. However, prospective studies have questioned this
      hypothesis. RECENT FINDINGS: Statins regulate beta-amyloid metabolism and
      microglial activation. Pathologically, patients with Alzheimer's disease have
      more severe atherosclerosis in cerebral arteries than do controls. Such lesions
      may cause cerebral hypoperfusion, a risk factor for dementia and cognitive
      decline. Although most population-based studies have failed to show a beneficial
      effect of statins in Alzheimer's disease, two randomized controlled trials
      suggested that statins slow cognitive decline in mild to moderate Alzheimer's
      disease. SUMMARY: There is still some hope that statins reduce the incidence of
      Alzheimer's disease and slow its progression. Large-scale randomized controlled
      trials of simvastatin and atorvastatin for mild to moderate Alzheimer's disease
      are underway, which might provide more conclusive results than earlier studies.

PMID- 16276239
TI  - Clinical implications for statin pleiotropy.
AB  - PURPOSE OF REVIEW: Atherosclerosis is a multi-factorial condition involving
      dyslipidemia that can result in cardiovascular disease. Statins are potent
      inhibitors of cholesterol biosynthesis, and in clinical trials, statins have been
      shown to be beneficial in the primary and secondary prevention of coronary heart
      disease. However, the overall benefits observed with statins appear to occur much
      earlier and to be greater than what might be expected from changes in lipid
      levels alone, suggesting effects beyond cholesterol lowering. SUMMARY OF
      FINDINGS: Recent studies indicate that some of the cholesterol-independent or
      'pleiotropic' effects of statins involve improving endothelial function,
      enhancing the stability of atherosclerotic plaques, decreasing oxidative stress
      and inflammation, and inhibiting the thrombogenic response. Many of these
      pleiotropic effects are mediated by inhibition of isoprenoids, which serve as
      lipid attachments for intracellular signaling molecules. In particular,
      inhibition of small GTP-binding proteins, Rho, Ras, and Rac, whose proper
      membrane localization and function are dependent upon isoprenylation, may play an
      important role in mediating the pleiotropic effects of statins. SUMMARY: The
      potential clinical implications of statin pleiotropy suggests that perhaps other
      biomarkers, in addition to lipid levels, should be used to gauge the full
      efficacy of statin therapy in patients with cardiovascular risks or that statin
      therapy may be effective in disease states, such as inflammatory conditions,
      ischemic stroke or cancer, where elevated cholesterol levels have not been shown
      to be a strong epidemiological risk for these diseases.

PMID- 16276240
TI  - Statin therapy in heart failure.
AB  - PURPOSE OF REVIEW: The 3-hydroxy-3-methylglutaryl-coenzyme-A reductase
      inhibitors, or statins, have been shown to reduce cardiovascular morbidity and
      mortality among a wide spectrum of patients with established atherosclerotic
      vascular disease. Mounting experimental and clinical evidence also suggest a
      potential benefit as well as theoretical harm of statin therapy in patients with
      heart failure. RECENT FINDINGS: This article briefly summarizes the therapeutic
      properties of statins that may be of benefit to patients with heart failure and
      the theoretical adverse effects of cholesterol reduction in this group of
      patients. A number of nonrandomized clinical studies over the past several years
      have shown an association between statin use and reduced overall mortality.
      Several large-scale randomized studies designed to confirm these findings are
      currently under way. SUMMARY: Statin therapy appears to improve clinical outcomes
      in patients with both ischemic and nonischemic cardiomyopathy independently of
      their cholesterol-lowering properties. The theoretical adverse properties of
      statins in heart failure patients have not been substantiated in small to medium
      sized clinical trials. Although the encouraging results of these preliminary
      studies suggest a role for statin therapy in heart failure, larger studies are
      needed to validate these findings. Several ongoing randomized trials are
      currently under way to evaluate the effect of statin therapy on cardiovascular
      outcomes in heart failure patients. The results of these studies, expected in the
      next several years, should provide scientific evidence for the role of statins in
      the treatment of failure.

PMID- 16276241
TI  - Beyond guidelines: achieving the optimum in LDL cholesterol control.
AB  - PURPOSE OF REVIEW: Despite clear treatment guidelines, a major part of the
      population is not achieving the recommended LDL cholesterol target levels. This
      fact is more prominent among high-risk populations in which the majority of
      patients are untreated or undertreated. RECENT FINDINGS: The review will
      elaborate on the key issues of treating large populations: patient compliance,
      drug efficacy, cost-benefit, and physician quality of care. SUMMARY: A programme
      aimed at improving control of hyperlipidemia should address all four issues. The
      primary care physician should be empowered and given tools for optimizing
      treatment.

PMID- 16276242
TI  - Statin-induced myositis: a commonly encountered or rare side effect?
AB  - PURPOSE OF REVIEW: Statins are well established as first-line agents for
      cholesterol lowering in cardiovascular disease, with accumulating evidence
      supporting their initiation and guidelines recommending treatment to lower LDL
      levels. Although generally well tolerated with few side effects, including
      headaches and gastrointestinal symptoms, concerns are raised regarding myopathy,
      which may lead to fatal rhabdomyolysis. This review examines current evidence on
      statin interactions, mechanism of injury and toxicity. RECENT FINDINGS:
      Significant myopathy is rare with an incidence of less than 0.5% of patients.
      Statin side effects may be dose-related, associated with other drug interactions
      that interfere with statin metabolic pathways through cytochrome p450 pathways or
      glucuronidation, or related to co-morbidities. Several theories have suggested
      that statin myotoxicity may be due to intracellular cholesterol depletion, or
      interference with oxidative phosphorylation pathways. Exact mechanisms are yet to
      be fully defined. Individuals with mixed dyslipidaemia may require combination
      therapy to achieve target lipid levels. No large-scale randomized trials have yet
      reported on the safety of combination therapy, although more recent studies may
      shed some light when they report. CONCLUSION: As most individuals on statins are
      'high-risk' patients, they tend to be on multiple agents for cardiovascular
      disease which may interact with their statin. Progression of myalgia or myositis
      to rhabdomyolysis is rare (one in 30-100,000 patient-years of exposure), but if
      progressive muscle symptoms are ignored then fatalities can occur. When
      prescribing statins, physicians should be alert to potential risks and educate
      patients to report any potentially significant symptoms.

PMID- 16276243
TI  - Role for fibrate therapy in diabetes: evidence before FIELD.
AB  - PURPOSE OF REVIEW: Diabetic dyslipidaemia, among the main factors contributing to
      vascular risk in type 2 diabetes, is characterized by hypertriglyceridaemia, low
      HDL-cholesterol and increased prevalence of small dense LDL particles. Because
      fibrates have positive effects on triglycerides, HDL-cholesterol and LDL particle
      size, they may be an appropriate treatment for diabetic dyslipidaemia. Statins
      have been shown to diminish significantly the risk for coronary disease in
      patients with type 2 diabetes, and so what are the real effects of fibrates on
      cardiovascular risk in type 2 diabetes? RECENT FINDINGS: Although statins reduce
      the incidence of coronary disease in type 2 diabetes, data from clinical trials
      demonstrate 'residual' cardiovascular risk in these patients treated with
      statins. Clinical trials with fibrates show that they are particularly effective
      in reducing cardiovascular risk in patients with type 2 diabetes/metabolic
      syndrome and in those exhibiting the lipid abnormalities typical of diabetic
      dyslipidaemia (elevated triglycerides, low HDL-cholesterol). SUMMARY: Data on the
      effects of fibrates on cardiovascular risk in diabetes were obtained from
      subgroup analyses. Thus far, the only study performed specifically in patients
      with type 2 diabetes is the angiographic Diabetes Atherosclerosis Intervention
      Study which demonstrated a significant reduction in progression of
      atherosclerosis in patients receiving fenofibrate, but it was not powered to
      analyse the effects of fibrates on clinical outcomes. This is why the Fenofibrate
      Intervention and Event Lowering in Diabetes study is needed; it will provide
      robust data on the ability of fibrates to reduce cardiovascular risk in patients
      with type 2 diabetes.

PMID- 16276245
TI  - Bibliography. Current world literature. Therapy and clinical trials.

PMID- 16276244
TI  - HDL-raising strategies in the treatment of coronary artery disease: perspectives
      from the Armed Forces Regression Study.
AB  - PURPOSE OF REVIEW: Even with the aggressive reduction of LDL-cholesterol, the
      risk of cardiovascular events in patients with coronary artery disease remains
      substantial. The Armed Forces Regression Study was a randomized, double-blind,
      placebo-controlled trial of combination drug therapy aimed at raising HDL
      cholesterol in patients with angiographically evident coronary artery disease.
      Drug therapy ultimately resulted in regression of the angiographic lesions and a
      reduction in cardiovascular events. This review places the Armed Forces
      Regression Study within the context of other recent studies. RECENT FINDINGS: In
      the past few years a number of other important papers have further defined the
      important role HDL-cholesterol plays in the pathobiology of atherosclerosis.
      These studies have focused on three general areas: HDL-cholesterol metabolism and
      the reverse cholesterol transport pathway; novel therapeutic interventions and
      their effects on coronary artery disease as assessed through non-invasive imaging
      modalities; and finally a re-analysis of previous outcomes trials with
      established HDL-cholesterol modifying agents. SUMMARY: The results of the Armed
      Forces Regression Study fit nicely within the evolving paradigm of targeting HDL
      cholesterol in patients at risk of cardiovascular events. The use of niacin and
      well-tolerated fibrates as an adjunct to statins or as primary therapy in
      patients intolerant of statins appears reasonable in patients with low levels of
      HDL-cholesterol and at high risk of cardiovascular events. The further
      development of novel therapeutic approaches, in addition to broadening our
      pharmacological armamentarium, should further advance our understanding of HDL
      cholesterol.

PMID- 16276247
TI  - Genetics and molecular biology.

PMID- 16276246
TI  - Nutrition and metabolism: the metabolic syndrome again!

PMID- 16276248
TI  - Lipid metabolism.

PMID- 16276249
TI  - Hyperlipidaemia and cardiovascular disease: triglycerides--new evidence for links
      with atherogenesis?

PMID- 16276250
TI  - Atherosclerosis: cell biology and lipoproteins--atherosclerosis and harbingers of
      cardiovascular disease start in childhood and adolescence.

PMID- 16276251
TI  - Therapy and clinical trials.

PMID- 16276252
TI  - 'Fire, earth, wind and water'.

PMID- 16276253
TI  - Disasters: experience and planning.

PMID- 16276254
TI  - Analysis of the pre-incident education and subsequent performance of emergency
      medical responders to the Volendam cafe fire.
AB  - OBJECTIVE: At this moment, in the Netherlands, rescue workers are not given any
      specific standardized training in disaster response or disaster management. After
      the cafe fire in Volendam, the Netherlands, on New Year's Eve 2000, around 200
      rescue workers were deployed on-site. The aim of this study is to investigate the
      rescue workers' experiences with regard to their level of preparation for the
      emergency response. METHODS: In 2002, 30 members of the medical and paramedical
      personnel were requested to participate in a structured interview, focused on
      education, task perception, triage and registration. RESULTS: Twenty-seven
      participated. Twenty-two rescue workers received previous training in emergency
      medicine. During the alarm phase, 11 rescue workers had a clear perception of
      their tasks. Twenty-four were involved in triage and injury assessment. Three
      rescue workers used a protocol for triage and 15 for injury assessment. Twenty
      five rescue workers gave on-scene treatment and 15 used a protocol. Eight
      registered their findings. CONCLUSIONS: Preparation for the emergency response
      lacked standardized procedures. The use of triage protocols was extremely poor,
      as was documentation of actions. Slightly more than half of the personnel
      followed treatment protocols. It is advisable that all rescue workers become
      familiar with the basic uniform principles and protocols regarding disaster
      management. A dedicated and standardized national disaster management course is
      needed for all rescue workers.

PMID- 16276255
TI  - Management of multiple burn casualties from the Volendam disaster in the
      emergency departments of general hospitals.
AB  - OBJECTIVE: To establish the level of medical care provided in the emergency
      department of general hospitals to the victims of the Volendam cafe fire on 1
      January 2001. METHODS: A retrospective review was done based on a standardized
      chart, for all victims seen at the emergency departments of 19 hospitals.
      Diagnostic findings and logistic aspects were inventoried. Treatment described in
      the Emergency Management of Severe Burns protocol was used as a gold standard
      against which the care provided to the victims was assessed. RESULTS: Data from
      233 patients were included in the analysis. The documentation rate was low.
      Suspected inhalation injury and burns were the most frequently documented
      diagnoses. Most patients with suspected inhalation injury, for whom treatment
      records were available, received oxygen therapy (81%). Intubation was performed
      in 43% of patients with suspected inhalation injury and 14% of the remaining
      patients required intubation after admission to the intensive care unit. Most
      patients with circulatory problems (83%) and/or more than 15% of total body
      surface area burned (97%), for whom treatment records were available, received
      intravenous lines. Pain treatment seemed to have had low priority. Two patients
      (3%) were re-admitted after having been released earlier from the emergency
      department. CONCLUSION: Treatment and triage of the burn casualties after the
      Volendam cafe fire was adequate. The documentation rate was low. Not all steps in
      diagnosis and treatment may be of equal importance in disaster circumstances.

PMID- 16276256
TI  - Emergency department assessment of abdominal pain: clinical indicator tests for
      detecting peritonism.
AB  - OBJECTIVES: Peritonism is a finding that leads to a more cautious approach in the
      emergency department management of abdominal pain. This study examined whether
      peritonism assessment using inspiration, expiration and cough tests was
      associated with the patient's clinical management. METHODS: This prospective
      observational study evaluated consecutive patients presenting directly to the
      emergency department for 3 months from June 2000 with abdominal pain. Triage
      initial observations of blood pressure, pulse, respiratory rate, oxygen
      saturation and temperature were recorded. The examining emergency physician
      recorded each patient's response and pain score to the individual peritonism
      tests and scored it as positive if there was an indication of it being a painful
      manoeuvre. The results were blinded from the receiving specialty if subsequent
      referral was required. RESULTS: Sixty-seven patients had peritonism tests
      performed. No individual test was more painful than the others with similar
      values in pain scores. In all, 70% (7/10) were admitted when all three tests were
      positive, compared with 21% (12/57) when two or less of the tests scored positive
      (P=0.004, Fisher's exact test). Admission was not associated with any individual
      test or combination of tests, or any other variable. The peritonism tests were
      not associated with any other physiological observation or measurement.
      CONCLUSIONS: These peritonism tests represent a simple investigation, and are
      significantly associated with admission when all three tests are positive. They
      seem to be a clinical predictor of cases in which continuing assessment was
      required, and may be useful as a departmental 'safety net' in the management of
      abdominal pain.

PMID- 16276257
TI  - Does the National Emergency X-ray Utilization Study make a difference?
AB  - OBJECTIVE: To assess whether the introduction of the National Emergency X-ray
      Utilization Study guidelines in a UK emergency department reduced the number of
      patients having cervical spine radiographs and altered the accuracy of diagnosis
      of cervical spine injury. METHODS: This was a prospective, observational study.
      The number of patients with recent neck injury who had cervical spine radiographs
      taken was assessed for 3 months before and three months after the introduction of
      the National Emergency X-ray Utilization Study guidelines to an urban emergency
      department in the UK. The number of injuries missed by emergency department
      doctors during the two 3-month periods was also recorded. RESULTS: Prior to using
      the guidelines, 252 of 715 patients (35%) were X-rayed and when using the
      guidelines, 268 of 706 patients (38%) were X-rayed. No significant difference was
      observed between the rates of X-ray in the two groups (P=0.288). No injuries were
      missed by emergency department doctors either before or after the introduction of
      the guidelines. CONCLUSION: Introduction of the National Emergency X-ray
      Utilization Study guidelines to a UK emergency department did not reduce the
      number of patients having cervical spine radiographs after neck trauma and had no
      effect on the pick-up rate for cervical spine injuries.

PMID- 16276258
TI  - The effect of colloidal fluid replacement on wound healing in an experimental
      sublethal hemorrhagic shock model.
AB  - OBJECTIVE: The aim of the study was to evaluate the effects of different
      resuscitation solutions on wound healing in an animal model of sublethal
      hemorrhagic shock. METHODS: Sublethal hemorrhagic shock was established by blood
      withdrawal until the mean arterial pressure fell to 40 mmHg within 15 min.
      Animals were resuscitated with four different solutions: group I (n=19) 0.9%
      NaCl, group II (n=20) 10% dextran 40, group III (n=20) 6% hydroxyethyl starch,
      group IV (n=18) 4% modified fluid gelatin. Following inhalation anesthesia, a
      full thickness skin incision of 2 cm in length was made on the abdominal wall and
      sutured primarily. The incision wound on the abdominal wall was excised on the
      fifth day. The breaking strength of the incision and hydroxyproline content of
      dry tissue were evaluated. RESULTS: Differences in breaking strength values were
      observed between groups I-III and I-IV (P<0.05). Hydroxyproline values were
      significantly lower in group IV (58.47 microg/ml) and group II (69.17 microg/ml)
      (P<0.05). The gelatin-resuscitated group had lower breaking strength and
      hydroxyproline values than the other groups. CONCLUSION: It can be concluded that
      resuscitation with modified fluid gelatin may have detrimental effects on wound
      healing in an experimental model of sublethal hemorrhagic shock.

PMID- 16276259
TI  - Can the height of fall predict long bone fracture in children under 24 months?
AB  - AIMS: It can be difficult to determine the exact mechanism of injury in infants
      and babies aged 24 months and under. Falls are the most common mechanism of
      injury in children. The purpose of this study is to identify the relationship
      between reported height of fall and long bone fracture. METHODS: All children
      aged under 24 months who sustained a fracture (in the year 2003) were identified
      prospectively on the departmental fracture database. These children were matched
      for age and sex with children identified as having fallen but not having
      sustained a fracture. RESULTS: Sixty-three children aged 24 months and under were
      studied. The median height of fall in this group was 48 cm and that in the
      control group was 20 cm, P<0.001. A significant correlation was observed between
      the height of fall (cm) and severity of injury (Pearson's correlation
      coefficient=0.255). Receiver operating characteristic analysis indicates that the
      likelihood of significant fracture requiring admission and/or manipulation under
      anaesthesia occurs with a fall from a height of 56 cm [sensitivity 80%
      (confidence interval 29-97%), specificity 79% (confidence interval 70-86%)]. It
      was not possible to identify a height at which the risk of any fracture injury
      became significantly more likely. CONCLUSION: Height of fall is only one factor
      that must be considered in dealing with fracture injury in children aged 24
      months or under. However, significant injury presenting with falls from less than
      50 cm should be critically evaluated.

PMID- 16276260
TI  - Mass casualty triage in the chemical, biological, radiological, or nuclear
      environment.
AB  - Field trauma triage systems currently used by emergency responders at mass
      casualty incidents and disasters do not adequately account for the possibility of
      contamination of patients with chemical, biological, radiological, or nuclear
      material. Following a discussion of background issues regarding mass casualty
      triage schemes, this paper proposes chemical, biological, radiological, or
      nuclear-compatible trauma triage algorithms, based on a review of the literature
      and the input of recognized content experts. A basic trauma triage template is
      first proposed, with patient assessment limited to ability to walk, presence of
      breathing, and ability to follow commands. This template is then modified for use
      in chemical, biological, and radiation/nuclear situations in which the exposed or
      contaminated victims have also sustained conventional trauma. The proposed
      algorithms will need further refinement and testing.

PMID- 16276261
TI  - Do patients with unrecognized coeliac disease present as an emergency?
AB  - Screening studies of healthy volunteers have determined that coeliac disease
      affects 1% of the European population. Despite this the majority of cases are
      unrecognized. Coeliac disease may occasionally present as an acute emergency.
      Recent data, however, suggest that cases of undiagnosed coeliac disease may
      present to emergency departments with nonspecific abdominal pain. This review
      provides an update of the published data on coeliac disease. We discuss the
      relationship between coeliac disease and abdominal pain and ways in which this
      may change emergency physicians practice.

PMID- 16276262
TI  - Severe rhabdomyolysis, acute renal failure and posterior encephalopathy after
      'magic mushroom' abuse.
AB  - We report the case of a 25-year-old, hepatitis C-infected man, who presented with
      severe rhabdomyolysis and acute renal failure, and later developed posterior
      encephalopathy with cortical blindness after the ingestion of magic mushrooms.
      Conventional respiratory and cardiovascular support including mechanical
      ventilation, continuous veno-venous hemodialysis and corticosteroids led to
      improvement and the patient recovered completely over the following months. Magic
      mushrooms are becoming increasingly fashionable among drug users, as they are
      believed to be more harmless than other hallucinogenic designer drugs. So far,
      little is known about their possible severe side effects.

PMID- 16276263
TI  - Metabolic hyperglycemic emergencies with acute pancreatitis in a child with known
      insulin-dependent diabetes mellitus.
AB  - The combined clinical and biochemical profile of diabetic ketoacidosis,
      hyperglycemic hyperosmolar non-ketotic syndrome, complicated by acute
      pancreatitis, in an 11-year-old with established insulin-dependent diabetes
      mellitus, is presented. The management requires diligent correction of
      dehydration and hyperglycemia, while monitoring neurological status and blood
      chemistry. It is imperative to monitor and avoid potentially fatal complications
      of the combined entity, namely, cerebral edema, thromboembolism, acute
      respiratory distress syndrome and rhabdomyolysis. Excluding acute pancreatitis in
      the face of persistent abdominal pain in this setting is emphasized.

PMID- 16276264
TI  - History of possible foreign body ingestion in children: don't forget the
      rarities.
AB  - Foreign body ingestion in children is a common presenting complaint to the
      emergency department. Although the majority of ingested foreign bodies pass
      through the gastrointestinal tract unaided, some children will require either non
      surgical or surgical intervention. Retained oesophageal foreign bodies may cause
      a multitude of problems, including mucosal ulceration, inflammation or infection,
      and more seriously paraoesophageal or retropharyngeal abscess formation,
      mediastinitis, empyema, oesophageal perforation and aorta-oesophageal fistula
      formation. We present a case of a 12-month-old child in whom delayed diagnosis of
      glass ingestion resulted in the development of a retropharyngeal abscess,
      oesophageal perforation and mediastinitis. Such complications following foreign
      body ingestion in children are rare but potentially fatal. A high index of
      suspicion must be maintained in young children presenting with a possible history
      of foreign body ingestion as a delayed diagnosis may lead to significant
      morbidity and mortality. We review the literature surrounding paediatric
      retropharyngeal abscesses and mediastinitis.

PMID- 16276265
TI  - Back pain in children: dig a bit deeper.
AB  - This report highlights the uncommon disease of Langerhans cell histiocytosis in
      the context of nontraumatic back pain. Langerhans cell histiocytosis has a broad
      range of presentations and should be borne in mind in many differential diagnoses
      in the emergency and general practice setting. Back pain in children, contrary to
      back pain in adults, is frequently the result of a treatable organic pathology
      and should be assessed thoroughly before a diagnosis of nonspecific or mechanical
      back pain is made.

PMID- 16276266
TI  - A case of severe hypercalcemia with acute renal failure in sarcoidosis: a
      diagnostic challenge for the emergency department.
AB  - We present and discuss the case of a man admitted to our emergency room because
      of severe hypercalcemia and renal failure with maintained diuresis. We diagnosed
      a relapse of sarcoidosis, manifesting as hypercalcemia and renal failure, based
      on a history of lung sarcoidosis. This is a rare complication of sarcoidosis, due
      to granulomatous production of vitamin D. This mechanism may have been
      exacerbated by exposure of sunlight. The initial treatment of the patient was
      directed towards lowering the circulating calcium level through hyperhydration
      and forced diuresis, with secondary control of granulomatous activity using
      corticosteroid therapy. The patient was discharged after 7 days with normal
      levels of serum calcium, urinary calcium excretion and serum creatinine.
      Recognition of this rare cause of hypercalcemia is a challenge for the emergency
      physician.

PMID- 16276267
TI  - Occult hypoglycemia in a diabetic patient on peritoneal dialysis.
AB  - In a patient with diabetes mellitus undergoing icodextrin continuous ambulatory
      peritoneal dialysis, the interference caused by icodextrin metabolites in bedside
      glucose analyzers led to an overestimation of capillary glucose levels and the
      potential for inappropriate therapy. We report this case to raise an awareness of
      this among emergency care providers who are at the front-line treating diabetes
      emergencies.

PMID- 16276268
TI  - Myasthenia gravis: lessons for the emergency physician.
AB  - We describe three patients with myasthenia gravis who presented to the emergency
      department - one with a previously established diagnosis and two others who were
      newly diagnosed as a result of workup initiated in the emergency department.
      Differential diagnosis of conditions causing neuromuscular weakness is broad;
      however, a key aspect of myasthenia gravis is fluctuating muscle weakness that
      increases with repeated use and improves with rest. Both newly diagnosed patients
      presented with ocular complaints, a common finding in myasthenia gravis. The
      third patient presented with a potentially life-threatening myasthenic crisis.
      Key points of discussion include: bedside tests to diagnose myasthenia gravis;
      distinction between cholinergic versus myasthenic crisis; and emergency
      department considerations when intubating a myasthenia gravis patient becomes
      necessary.

PMID- 16276271
TI  - Association between localized visual field losses and thickness deviation of the
      nerve fiber layer in glaucoma.
AB  - PURPOSE: To perform a correlation between morphology and function by studying
      local perimetric field losses and thickness reduction of the nerve layer in
      corresponding areas. METHOD: Forty-seven patients with "preperimetric" open-angle
      glaucoma, 95 patients with "perimetric" open-angle glaucoma, and 75 control
      subjects had perimetric (Octopus) and polarimetric measurements. Criteria for
      exclusion: optic discs larger than 4 mm, media opacities, polarimetric hourglass
      pattern in the macular image. Thickness values of the retinal nerve fiber layer
      were determined in 14 upper and 14 lower sectors (10 degrees each) as well as
      nasally and temporally (40 degrees each) as provided from the GDx (software
      version 4000). The healthy control subjects served to determine age-corrected
      thickness deviation in all sectors. Analyses were calculated in eight nerve fiber
      bundle related areas. Due to non-linear relationships between perimetric defects
      and corresponding thickness deviation non-parametric tests were used. RESULTS:
      Localized visual field defects in the present perimetric patients were highest in
      upper and lower visual field areas abutting the nasal meridian. Thickness loss of
      nerve fiber layer however was highest in more circumferential upper and lower
      nerve fiber bundles. Correlations between local mean defects and deviation of the
      retinal nerve fiber layer thickness from normals showed a clear association for
      corresponding areas. The correlation coefficients were significant (P < 0.01) for
      all arcuate superior and inferior visual field zones except horizontally and not
      for the area of the lower nasal step. CONCLUSION: The present correspondence map
      indicates that focal perimetric defects can be identified best polarimetrically
      if they occur in the arcuate bundles of the visual field. A lack of
      correspondence was observed in the area of the papillo-macular bundle.

PMID- 16276272
TI  - Repeat sample intraocular pressure variance in induced and naturally ocular
      hypertensive monkeys.
AB  - PURPOSE: To compare repeat-sample means variance of laser induced ocular
      hypertension (OH) in rhesus monkeys with the repeat-sample mean variance of
      natural OH in age-range matched monkeys of similar and dissimilar pedigrees.
      MATERIALS & METHODS: Multiple monocular, retrospective, intraocular pressure
      (IOP) measures were recorded repeatedly during a short sampling interval (SSI, 1
      5 months) and a long sampling interval (LSI, 6-36 months). There were 5-13 eyes
      in each SSI and LSI subgroup. Each interval contained subgroups from the Florida
      with natural hypertension (NHT), induced hypertension (IHT1) Florida monkeys,
      unrelated (Strasbourg, France) induced hypertensives (IHT2), and Florida age
      range matched controls (C). Repeat-sample individual variance means and related
      IOPs were analyzed by a parametric analysis of variance (ANOV) and results
      compared to non-parametric Kruskal-Wallis ANOV. RESULTS: As designed, all group
      intraocular pressure distributions were significantly different (P < or = 0.009)
      except for the two (Florida/Strasbourg) induced OH groups. A parametric 2 x 4
      design ANOV for mean variance showed large significant effects due to treatment
      group and sampling interval. Similar results were produced by the nonparametric
      ANOV. Induced OH sample variance (LSI) was 43x the natural OH sample variance
      mean. The same relationship for the SSI was 12x. CONCLUSION: Laser induced ocular
      hypertension in rhesus monkeys produces large IOP repeat-sample variance mean
      results compared to controls and natural OH.

PMID- 16276273
TI  - Audit of trabeculectomy at a tertiary referral hospital in East Africa.
AB  - AIM: To audit medium-term results of trabeculectomy at a tertiary referral unit
      in east Africa. METHODS: A retrospective review of the files of all patients who
      underwent trabeculectomy surgery at our hospital during the year 2001. RESULTS:
      One hundred fifty-seven patients were included. Mean age was 61 years (SD = 12).
      Thirty-one patients (20%) were women; 120 of 145 (83%) eyes had cup/disc ratios
      of 0.8 or greater preoperatively. Intraoperative 5-fluorouracil (5FU) was used in
      57 cases (36%). Mean follow-up was 8 months (0-28, SD = 7). Mean intraocular
      pressures (IOP) was 25 mm Hg (6-70, SD = 10) preoperatively, 11 mm Hg (0-32, SD =
      5) at 2 weeks postoperatively, and 13 mm Hg (0-42, SD = 6) at latest follow-up.
      One hundred fifteen patients (73%) had intraocular pressure of 15 mm Hg or less
      at latest follow-up and 141 (90%) had intraocular pressure of 21 mm Hg or less.
      Twenty (13%) had restarted antiglaucoma medication during the follow-up period.
      Thirty-seven of 148 (25%) lost 2 lines of Snellen acuity or equivalent between
      preoperative measurement and latest follow-up. Early postoperative complications
      (usually leaking bleb or shallow anterior chamber with hypotony) occurred in 18
      patients (12%) and this was associated with postoperative loss of 2 or more lines
      of Snellen acuity (OR = 1.11 95% CI 1.02-1.22, P= 0.02). Patients having had 5FU
      had lower (t = 3.11, P= 0.02) mean intraocular pressure at 2-month follow-up (12
      mm Hg, SD = 5) than those who did not receive it (16 mm Hg, SD = 6) but there was
      no significant difference at later follow-ups. Men (mean 14 mm Hg, SD = 6) had
      higher (t = 2.71, P= 0.01) intraocular pressures at latest follow-up than women
      (mean 11 mm Hg, SD = 3). CONCLUSIONS: The results of surgery compare well with
      other reported series. 5FU did not demonstrate significant benefit in terms of
      intraocular pressure lowering beyond 2 months postoperatively. Early
      postoperative hypotony should be avoided. The gender difference in intraocular
      pressure results has not previously been reported and deserves further
      investigation.

PMID- 16276274
TI  - Transconjunctival suture adjustment for initial intraocular pressure control
      after trabeculectomy.
AB  - PURPOSE: In an experimental human eye model of trabeculectomy, scleral flap
      suture adjustment allows predictable control of intraocular pressure (IOP). This
      approach had not previously been described in clinical use; we present a case
      series with the application of this technique. METHODS: A prospective, non
      comparative interventional case series of consecutive patients undergoing
      trabeculectomy. Forty trabeculectomies were performed using a 3 mm x 4 mm scleral
      flap with two apical adjustable 10-0 nylon sutures under a fornix-based
      conjunctival flap. Intraoperatively the scleral flap sutures were tied tightly to
      appose the edges of the flap. All trabeculectomies were augmented with
      antimetabolite intraoperatively. On day one, patients with an IOP greater than 15
      mm Hg had their suture tension adjusted to lower their IOP to a target range (10
      to 15 mm Hg). Major outcome measures were IOP before and after adjustment and
      success at last follow-up (IOP < or = 15 mm Hg on no glaucoma medication and no
      clinically significant complications) without and with adjunctive needling. Other
      outcomes measured were postoperative complications, bleb needling, final bleb
      morphology, and visual acuity change from pre-operation to final follow-up.
      RESULTS: Average day one IOP was 14.8 mm Hg (standard deviation (SD) 7.8).
      Fourteen patients had a day one IOP over 15 mm Hg and underwent suture
      adjustment, lowering IOP to between 10 and 15 mm Hg. (Mean post adjustment IOP
      was 10.7 mm Hg (SD 3.6)). One patient had a conjunctival tear intraoperatively.
      Four patients had transient wound leaks. No patients had shallow anterior
      chambers. All but four had diffuse blebs at last follow-up. Success rate without
      any further surgical intervention was 75%, and success rate with adjunctive
      needling was 100%. The mean duration of follow-up was 6.3 months (range 1-12
      months). CONCLUSION: The approach of tying scleral flap sutures tightly with
      transconjunctival adjustment of sutures if the IOP is greater than 15 mm Hg on
      day one allows excellent control of early postoperative IOP.

PMID- 16276275
TI  - Cyclosporin as an adjunct to glaucoma filtration surgery.
AB  - PURPOSE: Current adjunctive therapies to glaucoma surgery have unreliable
      effects, are toxic, and have numerous late complications associated with their
      use. This study examined whether topical cyclosporin (CsA) prolongs bleb survival
      after glaucoma filtration surgery. METHODS: Anesthetized white New Zealand
      rabbits underwent glaucoma filtration surgery with a drainage tube. Cyclosporin
      (2%), applied intraoperatively or as topical treatment following glaucoma
      filtration surgery, was compared with intraoperative mitomycin C (MMC) and an
      untreated control group. RESULTS: The bleb remained elevated for 15.1 +/- 3.2
      days in the untreated control group, 12.2 +/- 2.1 days after intraoperative
      cyclosporin, and 27.5 +/- 1.7 days after intraoperative mitomycin C (P < 0.001).
      When topical treatment with cyclosporin followed intraoperative mitomycin C, bleb
      survival significantly decreased to 19.2 +/- 4.6 days (P = 0.003). Intraocular
      pressure (IOP) remained significantly reduced in the mitomycin C-treated group
      longer than in either the control or cyclosporine-treated groups. CONCLUSIONS: In
      comparison with mitomycin C, neither intraoperative nor postoperative treatment
      with cyclosporin was associated with a decrease in intraocular pressure or
      prolonged bleb survival. Contrary to the initial hypothesis, topical treatment
      with cyclosporin actually mitigated the beneficial effects of mitomycin C on bleb
      survival. Clinical implications of these findings for patients with functioning
      blebs deserve further study.

PMID- 16276276
TI  - Correlation between finger blood flow and changes in optic nerve head blood flow
      following therapeutic intraocular pressure reduction.
AB  - PURPOSE: To correlate finger blood flow and changes in optic nerve head (ONH)
      blood flow following therapeutic intraocular pressure (IOP) reduction in open
      angle glaucoma (OAG) and ocular hypertension (OHT). METHODS: Seventeen open-angle
      glaucoma patients and nineteen ocular hypertension patients underwent therapeutic
      IOP reduction followed by a minimum of 4 weeks of follow-up. Optic nerve head
      blood flow measurements were obtained by scanning laser Doppler flowmetry using
      full-field perfusion image analysis. Finger blood flow was measured using the
      Transonic laser Doppler Flowmeter. Finger blood flow was measured at baseline,
      after immersion in warm water (40 degrees C) for 2 minutes (Flow Max), and after
      immersion in cold water (4 degrees C) for 10 seconds (Flow Min). Patients were
      identified as vasospastic if their Flow Max/Flow Min >7. Statistical comparisons
      were performed using two-tailed distribution paired T-test and Pearson's
      correlation factor. RESULTS: For similar mean percentage intraocular pressure
      reduction, vasospastic patients had greater improvements in rim blood flow than
      did non-vasospastic patients [+35% versus +13%] (P = 0.01). While there was no
      difference in rim blood flow changes in the vasospastic versus the non
      vasospastic OAG group, the vasospastic ocular hypertension group showed 18%
      increase in rim blood flow whereas the non-vasospastic ocular hypertension group
      showed an 8% decrease. A significant negative correlation was also found in the
      open-angle glaucoma group between rim blood flow change and Flow Max (-0.681, P =
      0.003). In contrast, no such correlation was found in the ocular hypertension
      group (+0.144, P = 0.556). CONCLUSION: OAG patients had a significant negative
      correlation between changes in rim blood flow and maximum finger Doppler flow.
      Among ocular hypertension patients, increased rim blood flow was only found in
      the vasospastic group, though this increase was not statistically significant.
      These results suggest that open-angle glaucoma and ocular hypertension patients
      with the most severe vasospastic disease may show the greatest improvements in
      rim blood flow after sustained intraocular pressure reduction.

PMID- 16276277
TI  - Utility values in Singapore Chinese adults with primary open-angle and primary
      angle-closure glaucoma.
AB  - PURPOSE: To evaluate utility values in Chinese glaucoma patients. PATIENT AND
      METHODS: Singapore Chinese residents (n = 213) with primary open-angle glaucoma
      or primary angle-closure glaucoma were recruited from a single tertiary
      ophthalmic center. Standard face-to-face interviews were conducted to ask about
      utility values (time trade-off and standard gamble for both death and blindness).
      Ocular information, including current visual acuity, intraocular pressure, visual
      field defect, and cup-disc ratio were also obtained. RESULTS: The mean time trade
      off utility value was 0.88 (95% confidence interval 0.85, 0.91), and standard
      gamble for death and blindness were 0.94 (95% confidence interval 0.93, 0.96) and
      0.95 (95% confidence interval 0.93, 0.97), respectively. Only 35.7% of patients
      were willing to trade time, and 34.3% willing to risk blindness in return for
      perfect vision. Both primary angle-closure glaucoma and primary open-angle
      glaucoma patients had similar utility values. After adjusting for age, gender,
      language spoken, educational level, and diagnosis, patients with better eye
      visual field PSD > 10 were 2.52 times (95% confidence interval 1.13, 5.61) more
      willing to trade time. In a multivariate model, the odds ratio of willingness to
      risk blindness for a complete hypothetical glaucoma cure was 9.88 (95% confidence
      interval 1.65, 59.23) for patients who had only visited an ophthalmologist 15
      years or more ago, and 0.53 (95% confidence interval 0.27, 1.02) for patients who
      had previous trabeculectomy. CONCLUSION: Most Chinese glaucoma patients in
      Singapore are not willing to trade time or risk blindness. Patients with worse
      visual fields in the better-seeing eye are more willing to trade time; whereas
      patients who have not seen an ophthalmologist for at least 15 years or who had no
      history of a previous trabeculectomy are more willing to risk blindness.

PMID- 16276278
TI  - Clinical outcomes of glaucoma treatments over a patient lifetime: a Markov model.
AB  - PURPOSE: To quantify the clinical outcome of glaucoma treatment over a patient's
      lifetime to identify treatment parameters that would preserve vision across a
      population. METHODS: A Markov model was used to reproduce glaucoma treatments and
      clinical responses over a patient's lifetime. Markov states comprised first-line
      to fourth-line pharmacological treatments, no treatment, laser therapy, surgery,
      blindness, and death. All patients began with first-line treatment and passed to
      the next treatment in line following a failure. After each failure, and always
      after a fourth-line failure, patients could receive laser therapy or surgery,
      followed by no treatment or a new first-line treatment. Transitional
      probabilities came from a cross-sectional study and national statistics.
      Sensitivity analyses were based on second order Monte-Carlo simulation. RESULTS:
      Cohort demographics were average age 59.7 years, life expectancy 22.5 years,
      females 54.0%. Treatment durations (months) for a patient with ocular
      hypertension were first-line (89), second-line (49), third-line (41), and no
      treatment (44); laser interventions numbered 1.251 and surgical 0.882. For a
      patient with glaucoma the corresponding values were 70, 44, 40, 18, 42, 1.197,
      and 0.842. First-line or second-line drugs best at controlling intraocular
      pressure (IOP) reduced laser therapy, surgery, and the prevalence of blindness.
      The most effective drug should be prescribed first-line. According to our model
      drugs specifically able to arrest disease progression would be more beneficial
      than intraocular pressure control. CONCLUSION: More powerful glaucoma medication
      (first-line or second-line) would contribute to the preservation of long-term
      vision.

PMID- 16276279
TI  - Glaucoma after ocular contusion: a cohort study of the United States Eye Injury
      Registry.
AB  - PURPOSE: This cohort study was designed to evaluate risk factors for the
      development of posttraumatic glaucoma after ocular contusion. METHODS: Data from
      the United States Eye Injury Registry (USEIR) were obtained from a total of 6021
      patients who experienced blunt ocular contusion. Logistic regression was used to
      evaluate the association between these baseline structural and functional ocular
      characteristics and posttraumatic glaucoma. Odds ratios with 95% confidence
      intervals were obtained. RESULTS: The 6-month incidence of developing
      posttraumatic glaucoma was 3.39%. The development of glaucoma was independently
      associated with: advancing age (OR = 1.02; 95% CI = 1.02, 1.03), visual acuity
      worse than 20/200 (OR = 1.92; 95% CI = 1.19, 3.10), iris injury (OR = 1.60; 95%
      CI = 1.05, 2.44), lens injury (OR = 1.86; 95% CI = 1.11, 3.11), hyphema (OR =
      2.23; 95% CI = 1.40, 3.54), or angle recession (OR = 1.71; 95% CI = 1.00, 2.90).
      CONCLUSION: This study provides an estimate for the risk of developing glaucoma
      after ocular contusion in a large cohort of patients and has determined several
      independently predictive factors that were significantly associated with the
      development of posttraumatic glaucoma including poor initial visual acuity,
      advancing age, lens injury, angle recession, and hyphema.

PMID- 16276280
TI  - Decreased response of plasma cortisol to intravenous metyrapone in ocular
      hypertension and primary open-angle glaucoma.
AB  - PURPOSE: To determine if there is a difference in response to metyrapone, which
      blocks the conversion of 11-deoxycortisol to cortisol in the adrenal gland
      between normals and ocular hypertensives (OH) plus primary open-angle glaucomas
      (POAG) without pigmented angles. METHODS: Intravenous metyrapone was given to 20
      normals and 15 ocular hypertensives plus primary open-angle glaucomas without
      pigmented angles. Blood samples were obtained at 4, 6, and 8 hours after
      administration of intravenous metyrapone for analyses of 11-deoxycortisol and
      cortisol. RESULTS: The ocular hypertensives plus primary open-angle glaucoma
      group showed significantly lower cortisol values compared with the normal group
      at 6 hours (P = 0.002) but not at 4 or 8 hours. There were no significant
      differences between the two groups for 11-deoxycortisol values at 4, 6, or 8
      hours. The percent decrease of plasma cortisol from baseline was significantly
      greater for the ocular hypertensives plus open-angle glaucoma group compared with
      the normals at 4 hours (P = 0.010) and 6 hours (P = 0.0004). Significant negative
      correlations were observed for the total group of subjects between levels of
      plasma cortisol at 6 hours and intraocular pressure, worse eye (P = 0.029),
      percent area of cupping, worse eye (P = 0.045), pallor, worse eye (P = 0.001),
      and visual field loss, worse eye (P = 0.048), so that the less the plasma
      cortisol, the greater the abnormality of the glaucomatous parameters.
      Multivariate analyses with the 6-hour plasma cortisol level as the dependent
      variable showed that the only significant (P = 0.0004) independent variable was
      the percent area of pallor, worse eye, associated with a smaller level of plasma
      cortisol at 6 hours. Similarly, the multiple regression models using the percent
      change from baseline of the 6-hour plasma cortisol value showed a significant
      association of larger percent decreases of plasma cortisol in the ocular
      hypertensives plus open-angle glaucoma compared with the normals. CONCLUSIONS:
      The ocular hypertensives plus primary open-angle glaucoma subjects show greater
      adrenal inhibition to metyrapone in the synthesis of cortisol from 11
      deoxycortisol compared with normals. This observation suggests an adrenal
      abnormality in the ocular hypertensive plus primary open-angle glaucoma subjects.

PMID- 16276281
TI  - The prevalence of pseudoexfoliation syndrome in a Japanese population: the
      Hisayama study.
AB  - PURPOSE: To examine the prevalence and systemic associations of pseudoexfoliation
      syndrome (PXS) in a Japanese population. METHODS: In 1998, a cross-sectional
      population-based survey was conducted among residents of Hisayama. Of a total of
      3054 residents living in Hisayama, Japan, aged 50 years or older, 1844 consented
      to participate in the study. Each participant underwent a comprehensive
      examination that included an ophthalmic examination. The presence of any
      pseudoexfoliation material on the iris or lens capsule was determined by slit
      lamp examination. The participants were classified as having pseudoexfoliation
      syndrome if any pseudoexfoliation material was present in either eye. Using these
      cross-sectional data, logistic regression analyses were performed to determine
      the systemic associations of pseudoexfoliation syndrome. The following eight
      possible correlates were considered: age, sex, hypertension, diabetes,
      hyperlipidemia, current smoker, alcohol intake, and body mass index. RESULTS:
      Among the subjects, 50 (3.4%) had pseudoexfoliation syndrome. The prevalence of
      pseudoexfoliation syndrome increased significantly with age. Multiple logistic
      regression analysis showed that age and hypertension were significantly
      associated with pseudoexfoliation syndrome. CONCLUSION: The prevalence of
      pseudoexfoliation syndrome in a Japanese population was 3.4%, and increased with
      age. This study suggests that hypertension strongly correlates with
      pseudoexfoliation syndrome in our population-based sample of Japanese subjects
      aged 50 years or older.

PMID- 16276282
TI  - Detecting glaucoma with frequency-doubling technology perimetry: a comparison
      between N-30 and C-20 screening programs.
AB  - PURPOSE: To evaluate the ability of frequency-doubling technology (FDT) perimetry
      in detecting glaucoma with N-30 and C-20 screening programs. METHODS: Eighty eyes
      of 80 patients were enrolled (40 glaucomatous, 40 controls). Humphrey achromatic
      perimetry (standard automated perimetry, SAP) was considered as the "gold
      standard" for diagnosis. To assess whether N-30 screening program could detect
      more initial glaucomatous defects than C-20, glaucomatous patients included 20
      cases with nasal step at SAP (pre-selected by medical chart inspection). Patients
      underwent two SAP examinations to confirm diagnosis; then two N-30 and two C-20
      screening tests with frequency-doubling technology were performed in a randomized
      sequence. Finally, a frequency-doubling technology N-30 full-threshold
      examination was performed. Several criteria to define abnormality at frequency
      doubling technology screening programs were evaluated. RESULTS: For both C-20 and
      N-30 screening programs, the best parameter to detect glaucoma was the presence
      of at least 1 point with P < 5% (sensitivity = 87.5% for both tests and
      specificity of 90% and 95% for C-20 and N-30, respectively). Both screening
      procedures obtained a lower sensitivity (75%) in patients with a nasal step,
      whereas frequency-doubling technology full-threshold program was able to detect
      the initial defects in all cases. CONCLUSIONS: N-30 and C-20 screening procedures
      obtained similar results in well-defined glaucoma patients in terms of
      sensitivity and specificity. In the presence of a standard automated perimetry
      nasal step, diagnostic ability with both frequency-doubling technology screening
      strategies decreased and one quarter of nasal steps went undetected.

PMID- 16276283
TI  - Donor scleral patch for treating hypotony due to leaking and/or overfiltering
      blebs.
AB  - OBJECTIVE: To report a modified technique of bleb revision with the use of a
      donor scleral patch in cases in which scleral melting did not allow effective
      suturing and closure of the aqueous leak. The suturing technique ensures tight
      adaptation of the scleral patch over the leaky region, and allows better
      controlled aqueous flow with loose suturing of the posterior edge of the scleral
      patch. METHODS: Records of patients who underwent bleb revision with donor
      scleral graft from 1997 to 2003 were reviewed retrospectively. Chart information
      including demographic and clinical data was recorded preoperatively and 1 day, 1
      week, 1 month, 6 months, and at final follow-up. RESULTS: Fifteen patients
      underwent this surgical procedure for bleb revision. The mean follow-up time was
      22.0 +/- 24.0 months (median = 8.0 months). The mean preoperative visual acuity
      was 20/50 and the mean intraocular pressure (IOP) was 2.9 +/- 2.3 mm Hg, which
      improved to 20/30 and 14.1 +/- 3.3 mm Hg respectively, on last follow-up.
      CONCLUSIONS: The scleral patch with 4-nylon sutures should be proposed in cases
      in which a macerated scleral bed is revealed during the revision. The loose
      suturing of the scleral patch at its posterior border was found to prevent
      intraocular pressure spikes.

PMID- 16276284
TI  - Is intraocular pressure in the early postoperative period predictive of
      antimetabolite-augmented filtration surgery success?
AB  - PURPOSE: To determine whether intraocular pressure (IOP) in the early
      postoperative period after trabeculectomy or combined phacoemulsification
      trabeculectomy, augmented with antimetabolite, correlates with IOP at one year in
      surgeries considered to be successful at that time point. DESIGN: Retrospective
      case series. METHODS: A chart review of antimetabolite-augmented surgical
      procedures done by DJG and JBS between January 1994 and November 2000 identified
      82 primary or secondary trabeculectomies and 53 combined phacoemulsification
      trabeculectomies with at least one year of follow-up. The success rate for each
      surgical subgroup was calculated and IOP on postoperative days (POD +/- SD) 1, 7
      (+/-2), 30 (+/-5), 90 (+/-10), and 180 (+/-20) was correlated with IOP at one
      year (POY 1, between month 12 and 15) using linear regression. IOP at each time
      point was compared among eyes that achieved success at one year with and without
      the use of IOP-lowering agents. RESULTS: Of the 82 eyes having undergone
      antimetabolite-augmented trabeculectomies and the 53 eyes having undergone
      combined surgeries with at least one year of follow-up, the surgical success
      rates at POY 1 were 87.8% (72 of 82 eyes) and 92.5% (49 of 53 eyes). Of these, 42
      eyes (58.3%) from 39 patients in the trabeculectomy group and 27 eyes (55.1%)
      from 24 patients in the combined surgery group did not require glaucoma
      medications at one year postsurgically, and were considered complete surgical
      successes. Mean preoperative IOP mm Hg +/- SD was 26.0 +/- 8.5 for the
      trabeculectomy group and 18.2 +/- 4.5 for the phaco-trabeculectomy group.
      Postoperative IOP at POD 1, POD 7, POD 30, POD 90, POD 180, and POY 1
      respectively for the eyes undergoing trabeculectomy were 13.9 +/- 10.4, 9.5 +/-
      6.2, 12.0 +/- 5.5, 12.0 +/- 5.2, 12.8 +/- 5.9, and 12.1 +/- 4.3, and for the
      combined surgery group were 20.8 +/- 12.5, 9.7 +/- 5.7, 12.2 +/- 5.4, 11.1 +/-
      3.4, 11.6 +/- 4.6, and 10.3 +/- 4.3. Intraocular pressure on postoperative day
      one correlated poorly with intraocular pressure at POY 1 for the trabeculectomy
      group (R2 = 0.0788), and not at all for the combined procedures group (R2 =
      0.018). The correlation was slightly better for intraocular pressure at
      postoperative day 90 for the trabeculectomy group (R2 = 0.546), and at
      postoperative day 180 for the combined group (R2 = 0.37), but still rather low.
      Eyes requiring glaucoma medication use at POY 1 in the trabeculectomy group had
      higher (P < 0.009) intraocular pressure at POD 30 and at all subsequent visits
      than eyes not requiring these medications. Eyes requiring glaucoma medication use
      at POY 1 in the phaco-trabeculectomy group had higher (P < 0.0025) intraocular
      pressure at POD 30, POD 180, and POY 1 than eyes not requiring these medications.
      CONCLUSION: Intraocular pressure in the early postoperative period correlates
      very poorly with intraocular pressure one year after successful antimetabolite
      augmented trabeculectomy or combined cataract extraction and trabeculectomy.
      Starting one month after glaucoma surgery, intraocular pressure is substantially
      lower in eyes that will ultimately not require the use of ocular hypotensive
      agents to achieve clinical success one year postoperatively.

PMID- 16276286
TI  - Does extended wear of a tight necktie cause raised intraocular pressure?
AB  - PURPOSE: To investigate the effect that extended wear of a tight necktie has on
      the intraocular pressure (IOP), measured by Goldmann applanation tonometry in a
      normal and aged-matched glaucoma group. METHODS: One eye of 18 normal and 19
      primary open-angle glaucoma patients was included in this prospective study. The
      intraocular pressure of each patient's randomly selected eye was measured with
      the patient dressed in an open shirt collar, again 3 minutes after their collar
      was fastened and necktie tightened, again after a further 12 minutes, and finally
      3 minutes after the necktie was loosened and collar unfastened. The same examiner
      performed all measurements in a masked fashion. RESULTS: The mean intraocular
      pressure in the normal group (n = 18) increased by 0.56 mm Hg (P = 0.30) and
      increased significantly (*) in the glaucoma group (n = 19) by 1.58 mm Hg (P =
      0.001*) after tightening the necktie for 3 minutes. The mean IOP then decreased
      after leaving the necktie on for a further 12 minutes, by 0.89 mm Hg (P = 0.08)
      in the normal group and decreased significantly by 0.94 mm Hg (P = 0.04*) in the
      glaucoma group. Finally after loosening the necktie for 3 minutes (immediately
      after 15 minutes of continuous necktie wear) the mean IOP decreased in the normal
      group by 0.89 mm Hg (P = 0.02*) but only minimally in the glaucoma group by 0.16
      mm Hg (P = 0.72). The patient's age or collar size showed no significant
      correlation with the change in mean IOP following tight necktie wear. CONCLUSION:
      A significant increase in IOP after 3 minutes of tight necktie wear occurred only
      in the glaucoma group, but this increase was followed by a significant decrease
      in IOP after 15 minutes of tight necktie wear. Avoidance of wearing a tight
      necktie over an extended period is therefore not necessary in patients with
      glaucoma.

PMID- 16276285
TI  - Effects of caffeine on intraocular pressure: the Blue Mountains Eye Study.
AB  - PURPOSE: To examine the relationship between coffee and caffeine intakes and
      intraocular pressure (IOP). MATERIALS AND METHODS: The Blue Mountains Eye Study
      examined 3654 participants aged 49+ years in an area west of Sydney, Australia. A
      detailed medical history questionnaire included average daily intakes of coffee
      and tea. The eye examination included Goldmann applanation tonometry and
      automated perimetry. Participants using glaucoma medications or who had previous
      cataract or glaucoma surgery or signs of pigmentary glaucoma/pigment dispersion,
      were excluded. Mean and maximum IOP calculations were used. RESULTS: Participants
      with open-angle glaucoma (OAG) who reported regular coffee drinking had
      significantly higher mean IOP (19.63 mm Hg) than participants who said that they
      did not drink coffee (16.84 mm Hg), after multivariate adjustment, P = 0.03.
      Participants consuming > or = 200 mg caffeine per day had higher mean IOP (19.47
      mm Hg) than those consuming < 200 mg caffeine per day (17.11 mm Hg), after
      adjusting for age, sex, and systolic blood pressure (SBP), P = 0.06. This
      association did not reach statistical significance after multivariate adjustment.
      No association between coffee or caffeine consumption and higher IOP was found in
      participants with ocular hypertension (OH) and those without open-angle glaucoma.
      CONCLUSIONS: In participants with open-angle glaucoma, this study identified a
      positive cross-sectional association between coffee consumption/higher caffeine
      intakes and elevated intraocular pressure.

PMID- 16276287
TI  - Failed trabeculectomy.

PMID- 16276290
TI  - Battle influenza by being prepared.

PMID- 16276289
TI  - Precision and accuracy of Proview tonometer: clinical implications for self
      tonometry.

PMID- 16276291
TI  - Infective endocarditis guidelines assist in early identification.

PMID- 16276294
TI  - The cost of getting your business off the ground.

PMID- 16276295
TI  - The doctorate of nursing practice: a natural evolution.

PMID- 16276296
TI  - New markers for CVD.

PMID- 16276298
TI  - Graves' disease: the importance of early diagnosis.

PMID- 16276300
TI  - Fracture risk in postmenopausal women.

PMID- 16276301
TI  - Guide to care for patients. Type 2 diabetes.

PMID- 16276302
TI  - Field guide to pain: part 3: care after a pain management referral.

PMID- 16276309
TI  - Glumetza offers once-a-day dosing for type 2 diabetes patients.

PMID- 16276315
TI  - Just the facts.

PMID- 16276318
TI  - Face recognition in the elderly.
AB  - PURPOSE: The purpose of this study was to assess face recognition ability in a
      large sample of elders (n=572, mean age=78.1 years) and to identify factors that
      affect performance. METHODS: Face recognition was measured by presenting
      standardized faces of varying sizes to simulate normal-sized faces at different
      viewing distances. Subjects were asked to identify the name of the person and
      their facial expression. Threshold equivalent viewing distance (EVD) was
      calculated. High- and low-contrast acuity, contrast sensitivity, low-contrast/low
      luminance acuity, disability glare, stereoacuity, and visual field measures (with
      and without an attentional task) were also measured. These vision measures, along
      with demographic information (age, sex, education) and cognitive status, were
      included in a multiple regression analysis to determine which factors predicted
      task performance. RESULTS: This cross-sectional sample of elders showed
      significant declines in face recognition with age. Mean threshold EVD ranged from
      8.0 m for participants<or=70 years of age to 2.2 meters for those over 85 years.
      Multiple regression analysis revealed that age, sex, years of education, spatial
      vision, and cognitive status were all significant predictors of face recognition,
      accounting for approximately 46% of the variability. Spatial vision (high
      contrast acuity) and age were the best predictors. Although each spatial vision
      measure was significantly correlated with face recognition, adding low-contrast
      or contrast sensitivity measures to the regression analysis explained no more
      variance than age and high-contrast acuity alone. CONCLUSIONS: The marked decline
      in face recognition ability in elders is related to declines in spatial vision
      and cognitive status. All spatial vision measures have similar predictive ability
      for face recognition.

PMID- 16276319
TI  - Evaluation of the new web-based "Colour Assessment and Diagnosis" test.
AB  - PURPOSE: The purpose of the study was to determine the sensitivity, specificity,
      and repeatability of the web-based Colour Assessment and Diagnosis (CAD) test in
      comparison to current tests of color vision. METHODS: Thirty color normals and 30
      color deficients, identified and diagnosed by the Nagel anomaloscope, were
      tested. The results of the CAD test were compared with standard tests like Nagel
      anomaloscope, Ishihara (concise version, 2001), Hardy, Rand and Rittler (HRR; 4
      ed) pseudoisochromatic test, and the Farnsworth Munsell 100 (FM-100) hue test.
      RESULTS: Using the Nagel anomaloscope as the "gold standard," the sensitivity
      with the CAD test was 93.33%, Ishihara 96%, HRR 100%, and the FM-100 hue 100%.
      The specificity was 100% with CAD and the Ishihara color plates, whereas it was
      33% with the HRR and 83% with the FM-100 hue test. The concurrent validity of the
      CAD test for color normals was 93.75%. The concurrent validity of CAD test for
      color deficiency was 100%. Thus, anyone failing the CAD test has a color defect.
      The coefficient of agreement for the Nagel anomaloscope and the CAD test was
      0.93, with Ishihara it was 0.96, with the HRR it was 0.33, and with FM-100 hue it
      was 0.83. CONCLUSION: These results showed that the CAD test is a valid test for
      identifying congenital red-green color deficiency. Further testing is required in
      a larger population of anomalous trichromats.

PMID- 16276320
TI  - Overnight corneal reshaping versus soft disposable contact lenses: vision-related
      quality-of-life differences from a randomized clinical trial.
AB  - PURPOSE: The purpose of this article is to evaluate patients' visual acuity,
      symptoms, and perceptions of vision-related quality of life in a randomized
      crossover clinical trial of overnight corneal reshaping (OCR) and daily wear soft
      lenses (SCL). METHODS: Qualified subjects were randomly assigned to wear one mode
      of contact lens for 8 weeks and then, after a washout period, they wore the
      alternate mode for 8 weeks. On concluding each contact lens wear mode, subjects
      completed the NEI-RQL42 questionnaire. During the SCL mode, subjects wore lenses
      during their waking hours. During the OCR mode, subjects wore lenses only while
      sleeping. Soft lenses were Biomedics 55 2-week disposable lenses. OCR lenses were
      CRT lenses by Paragon. (Three subjects were fit with custom-designed OCR lenses
      in Boston XO material, manufactured by Art Optical.) LogMAR acuity was measured
      and slit lamp evaluation was performed at specified intervals during follow up.
      After completing both phases of the study, patients chose which mode they
      preferred. RESULTS: Of 81 enrolled patients, 65 completed both phases and 16
      dropped out during the study. Significant differences (p<0.01) favoring SCL wear
      included better visual acuity and less trouble with glare. Significant
      differences (p<0.01) favoring OCR wear included less activity limitations, less
      trouble with symptoms, and less dependence on refractive correction. Of 65
      completing both phases, 44 preferred the OCR lenses and 21 preferred the soft
      lenses. Subjects who preferred the OCR lenses were less myopic and had steeper K
      readings at baseline, and showed less difference between visual acuity during OCR
      wear and visual acuity with SCL. CONCLUSION: In subjects with mild myopia who
      experienced both SCL and OCR, better visual acuity and less glare resulted from
      SCL wear, whereas activity limitations, symptoms, and dependence on refractive
      correction were less troublesome with OCR wear. When the study was completed,
      67.7% chose OCR lenses worn only while sleeping, whereas 32.3% preferred 2-week
      disposable soft lenses worn during the day as their preferred correction.

PMID- 16276321
TI  - Repeatability and reproducibility of central corneal thickness measurement with
      Pentacam, Orbscan, and ultrasound.
AB  - PURPOSE: The purpose of this study was to compare central corneal thickness (CCT)
      measurements obtained with a novel rotating Scheimpflug camera (Pentacam; Oculus)
      with scanning slit topography (Orbscan; Bausch & Lomb), and with ultrasound
      pachymetry (SP-2000; Tomey). METHODS: CCT in 30 healthy eyes was measured twice
      with each modality by 2 independent observers in random order. The results from
      scanning slit topography are given both with and without multiplication with the
      "acoustic correction factor" of 0.92. In addition, the displayed images from the
      rotating Scheimpflug camera and scanning slit topography were used to calculate
      the signal difference-to-noise ratios (SD/N) between cornea and background
      signal. RESULTS: The mean CCT values as determined with the different modalities
      (+/-standard deviation) were: 542+/-29 microm, 576+/-37 microm, 530+/-34 microm,
      and 552+/-32 microm for rotating Scheimpflug imaging, for uncorrected and for
      corrected scanning slit pachymetry, and for ultrasound, respectively. The
      differences between modalities (+/-95% limits of agreement) were -9.8+/-31 microm
      between rotating Scheimpflug and ultrasound, 24+/-31.2 microm between scanning
      slit and ultrasound, and 33+/-27 microm between scanning slit and rotating
      Scheimpflug imaging. The limits of agreement for within and between observer
      effects were within 4.2% of the absolute CCT values for scanning slit and
      ultrasound and within 2.2% for the rotating Scheimpflug imaging. The rotating
      Scheimpflug camera showed similar SD/N ratios but steeper edges of the corneal
      surfaces in the intensity profile plots. CONCLUSION: In the assessment of normal
      corneas, the Pentacam measured CCT values closer to ultrasound pachymetry and
      with less variability compared with Orbscan. The (interobserver) reproducibility
      with the Pentacam was highest of all 3 modalities.

PMID- 16276323
TI  - Blink rate decreases with eyelid squint.
AB  - PURPOSE: We hypothesize that eyelid squint inhibits blink rate. This is part of a
      larger hypothesis that, because eyelid squint improves vision under conditions of
      optical defocus and/or glare, and reduced blink rate is assumed to contribute to
      dry eye symptoms, eyelid squint is part of the mechanism resulting in asthenopia.
      This study investigates the effect of voluntary eyelid squint on blink activity
      and on electromyography (EMG) measures from the orbicularis oculi. METHODS: Ten
      subjects (18 to 38 years of age) performed 3 1-minute trials each (Latin Square
      order) of voluntary target squint levels of 5%, 20%, 35%, and 50% with respect to
      previously demonstrated 0% (relaxed) and 100% (maximum) squint levels. EMG
      recordings using surface electrodes were obtained from the orbicularis muscle.
      Vertical dimension of the palpebral fissure and eye lid blinks were measured with
      an ISCAN eye tracker and video recorder. RESULTS: Each target squint level
      produced significant changes (p<0.0001) in ocular aperture size, EMG power, and
      EMG amplitude. For target voluntary squint levels of 5%, 20%, 35%, and 50%, the
      mean squint responses were 24%, 35%, 42%, and 53%, respectively. Blink rate was
      inversely related to both target squint level and squint response (p<0.0001),
      decreasing from 15 blinks per minute at 0% squint to 7.5 blinks per minute at 5%
      target voluntary squint and to 4 blinks per minute at 50% target voluntary
      squint. CONCLUSIONS: Voluntary eyelid squint significantly reduces blink rate by
      an average of 50% or more dependent on attempted level. Further study is required
      to determine if involuntary squint causes the same. All tested levels of
      voluntary squint resulted in an EMG signal from the orbicularis muscle that is
      measurably different from resting state. This indicates that EMG can be used as a
      reliable indicator of eyelid squint.

PMID- 16276322
TI  - Anterior chamber depth measurement with a-scan ultrasonography, Orbscan II, and
      IOLMaster.
AB  - PURPOSE: The authors conducted a comparison of anterior chamber depth (ACD)
      measurement by 3 devices of EchoScan, Orbscan II, and IOLMaster to assess the
      validity of the latter 2 and its reliability with Orbscan II. METHODS: Forty-four
      myopic patients, 56.8% female, were enrolled in this prospective study. In all 88
      eyes, the ACD was first measured with Orbscan II, followed by IOLMaster and
      EchoScan U3300, both under cycloplegia. The mean (+/-standard deviation) age and
      spherical equivalent were 30.2+/-8.5 years and -4.98+/-2.67 D, respectively. The
      difference between ACD measurements by these 3 devices was analyzed using the
      repeated-measures analysis of variance. Agreement between each pair of devices
      was assessed by computing the 95% limits of agreement (LoA). Orbscan II
      reliability was also evaluated by using the 95% LoA between 2 consecutive
      measurements. P value adjustments for multiple comparisons were performed using
      the Bonferroni method. RESULTS: There was a statistically significant difference
      between measurements made with the 3 devices (p<0.001). The mean difference
      between Orbscan II and Echoscan ACD measurements was -0.03+/-0.12 mm, with the
      95% LoA from -0.25 to +0.20 mm, and between IOLMaster and Echoscan measurements,
      it was +0.09+/-0.14 mm with the 95% LoA from -0.18 to +0.36 mm. On average,
      Orbscan II readings were lower and those of IOLMaster were higher than Echoscan
      readings. Both Orbscan II and IOLMaster agreed with Echoscan in measuring ACD.
      The 2 readings by Orbscan II had a 95% LoA of -0.05 and +0.07 mm that shows good
      reliability. CONCLUSION: ACD measurement differences with the 3 studied devices
      proved to be statistically significant; however, these minor differences may be
      clinically negligible depending on the use of the measurement. As an advantage,
      both Orbscan II and IOLMaster are noncontact, and with their ACD measurements
      being valid, they may be considered suitable devices for this purpose. In
      addition, Orbscan II produces highly repeatable ACD measurements.

PMID- 16276324
TI  - Randot stereoacuity does not accurately predict ability to perform two practical
      tests of depth perception at a near distance.
AB  - PURPOSE: It is common practice to administer stereopsis tests such as the Randot
      Stereotest to prospective employees for occupations requiring depth perception.
      However, there is no evidence that stereoacuity measured with tests such as the
      Randot Stereotest will predict an individual's ability to perform a depth
      perception task at near. METHODS: Forty-eight people with normal binocular vision
      were tested on 2 practical depth perception tests, and their stereoacuity was
      measured with the Randot Stereotest. RESULTS: There was little correlation
      between stereoacuity and either of the practical tasks (r<+/-0.1). CONCLUSIONS:
      These results show that Randot stereoacuity does not reliably predict depth
      perception ability for people who enjoy normal binocular vision. A better method
      for determining depth perception ability might be to issue a practical depth
      perception task.

PMID- 16276325
TI  - Progressive powered lenses: the Minkwitz theorem.
AB  - PURPOSE: The Minkwitz theorem, which can be proven to apply to the immediate
      surface surrounding a line of umbilics, states that astigmatism perpendicular to
      the line changes twice as quickly as the rate of change of power along the line.
      Our objective is to test how the Minkwitz theorem applies to the design of
      progressive addition lenses (PALs). METHOD: Our primary investigation of the
      astigmatism/power rate relationship used Hoya Tact lenses because they have a
      relatively large central region with horizontal spherical equivalent power
      contours and vertical astigmatism power contours. Other PALs were used for
      subsequent analysis. Lenses were measured with a Rotlex Class Plus lens analyzer.
      RESULTS: Zone widths in the central region of the Tact lenses exceeded those
      predicted by the Minkwitz theorem. Above and below this region, zone widths were
      narrower than predicted. When averaged along the entire corridor, zone widths
      approximated the Minkwitz theorem. For other PALs, the measured zone widths
      exceed Minkwitz theorem in the top (distance) and middle (intermediate) corridor
      but fell short in the lower (near) corridor. Likewise, on average along the
      entire corridor, they approximate the Minkwitz theorem. CONCLUSIONS: Although the
      Minkwitz theorem must apply exactly to the immediate locale of an umbilic,
      deviations from Minkwitz can occur within 2 mm of the corridor. Several factors
      enable enough local deviation from the Minkwitz theorem to "steer" the
      astigmatism and affect its magnitude in the peripheral portions of a lens.
      Although the Minkwitz relationship may be altered in some regions of the
      corridor, there is a global component to the Minkwitz prediction that applies to
      PALs. On a global level, the gains and losses of astigmatism along the corridor
      with respect to the Minkwitz prediction have strong tendency to cancel one
      another. In the end, it appears the unwanted astigmatism associated with a given
      power change along a given distance can be redistributed but probably not
      reduced.

PMID- 16276326
TI  - Paraxial propagation of astigmatic wavefronts in optical systems by an augmented
      stepalong method for vergences.
AB  - PURPOSE: The propagation of astigmatic wavefronts through astigmatic optical
      systems is reconsidered in the wavefront perspective. METHODS: The stepalong
      method for vergences, described by 2x2 matrices, is applied and augmented to
      produce off-axis information like the magnification. This so-called augmented
      stepalong method (ASAM) is derived by applying the paraxial propagation of
      astigmatic wavefronts to tilted wavefronts as well. RESULTS: The features of the
      ASAM are discussed for a single surface, a thick lens, and a general system.
      CONCLUSIONS: The ASAM provides all necessary information to describe a centered
      astigmatic optical system in paraxial approximation.

PMID- 16276327
TI  - Toward a new paradigm in hospital-based pediatric education: the development of
      an onsite simulator program.
AB  - OBJECTIVE: The low incidence of crises in pediatrics, coupled with logistic
      issues and restricted work hours for trainees, hinders opportunities for frequent
      practice of crisis management and teamwork skills. We hypothesized that a
      dedicated simulator suite contiguous to the intensive care unit (ICU) would
      enhance the frequency and breadth of critical-incident training for a range of
      clinicians. DESIGN: Descriptive study. SETTING: A tertiary-care pediatric
      teaching hospital. MEASUREMENTS AND MAIN RESULTS: A realistic pediatric simulator
      suite was constructed 100 feet from the ICU, at a total base cost of $290,000.
      The simulation room is an exact replica of an ICU bed space, incorporating high
      fidelity mannequin simulators. To capture an even wider audience, a portable unit
      was also created. Leaders from seven departments-critical care, cardiac intensive
      care, emergency medicine, transport medicine, anesthesia, respiratory care, and
      general pediatrics-completed instructor training to ensure effective debriefing
      techniques. Pediatric staff, including 100% of critical care fellows, 86% of
      nurses, 90% of respiratory therapists, and 74% of pediatric house staff,
      participated in >1500 learning encounters per year. All individuals were trained
      during their normal workday in the hospital. Courses in crisis resource
      management, skills acquisition, annual review, orientation, and trauma management
      (1,116, 98, 90, 60, and 60 encounters per year, respectively) were all designed
      by a multidisciplinary committee to ensure goal-directed education to a range of
      audiences. Annual costs were on par with those at other centers (approximately 44
      dollars per trainee encounter). CONCLUSIONS: An onsite and comprehensive
      simulation program can significantly increase the opportunities for clinicians
      from multiple disciplines, in the course of their daily routines, to repetitively
      practice responses to pediatric medical crises. After an initial capital
      investment, the training appears to be cost-effective. Hospital-based simulator
      suites may point the way forward as a new paradigm for the effective education of
      today's busy clinicians.

PMID- 16276329
TI  - Correlation of the Bispectral Index Monitor with the COMFORT scale in the
      pediatric intensive care unit.
AB  - OBJECTIVE: The COMFORT scale is a commonly used observational scoring system to
      assess the level of sedation in ventilated children in pediatric intensive care
      units (PICUs). The bispectral index (BIS) monitor is a processed
      electroencephalographic parameter that noninvasively measures the hypnotic effect
      of anesthetic and sedative drugs on the brain. The objective of this study was to
      assess the degree of correlation between the COMFORT scale and the BIS monitor.
      DESIGN: A prospective study in a tertiary level PICU. RESULTS: A total of 75
      children were enrolled in the study, resulting in 869 valid paired observations
      of BIS values and COMFORT scores. The median age was 10 months, with a range of 1
      month to 12 yrs. The median COMFORT score was 11 (range, 8-40). The median BIS
      value was 52 (range, 0-98). In a repeated-measures analysis, the correlation
      coefficient between COMFORT scores and BIS values averaged over time was 0.61 (p
      < .0001). CONCLUSIONS: The BIS monitor may be a valid and useful monitor of the
      level of sedation of children in the PICU. We cannot expect perfect correlation
      between BIS values and observational scales because they measure different
      variables. The BIS monitor may be the best objective monitor currently available
      for children receiving neuromuscular blockade because it does not rely on
      subjective measures such as those used in the COMFORT scale. The ability of the
      BIS monitor to distinguish between very deep levels of sedation may be useful to
      prevent over-sedation of children in PICUs and to help clarify the appropriate
      target level of sedation for each child.

PMID- 16276328
TI  - Cumulative fluid intake minus output is not associated with ventilator weaning
      duration or extubation outcomes in children.
AB  - OBJECTIVE: The effect of fluid balance on respiratory outcomes for critically ill
      children has not been evaluated. The only indicator of fluid balance routinely
      recorded across our intensive care units was estimated fluid intake and output.
      We sought to determine whether cumulative intake minus output (I-O) at the start
      of weaning predicted weaning duration and whether cumulative I-O at extubation
      predicted extubation failure. DESIGN: Prospective observational study. SETTING:
      Ten pediatric intensive care units. PATIENTS: Cumulative I-O was recorded daily
      for 301 mechanically ventilated children (<18 yrs of age) from November 1999
      through April 2001. INTERVENTIONS: Cumulative I-O was recorded during a study of
      weaning strategies and extubation failure in which mechanical ventilation of the
      majority of patients during weaning and extubation was managed according to a
      protocol that did not include fluid balance indicators. Outcomes were the time to
      successful removal of ventilatory support and the rate of initial extubation
      failure. MEASUREMENTS AND MAIN RESULTS: Relationships between cumulative I-O and
      outcomes were assessed by means of proportional hazards and logistic regression.
      The mean cumulative I-O per kilogram of ideal body weight at the start of weaning
      was 101 mL (sd, 180). Cumulative I-O at the time weaning was initiated did not
      predict duration of mechanical ventilator weaning. The mean cumulative I-O per
      kilogram of ideal body weight at extubation was 136 mL (sd, 237). Cumulative I-O
      at extubation did not predict extubation outcome. There was an association
      between cumulative I-O at extubation and the duration of weaning in cases not
      managed by a protocol. CONCLUSION: Although routinely recorded, cumulative fluid
      I-O does not appear to have clinical utility in cases managed according to a
      mechanical ventilator protocol in which tidal volume and oxygenation on minimal
      levels of ventilator support are systematically tested.

PMID- 16276332
TI  - Predictive factors for the success of noninvasive mask ventilation in infants and
      children with acute respiratory failure.
AB  - OBJECTIVE: Noninvasive mask ventilation (NIV) is a treatment option in acute
      respiratory failure in adults. This study was performed to determine prognostic
      variables for the success of NIV in a group of infants and children with
      respiratory failure for a wide range of reasons. DESIGN: Prospective, clinical
      study. SETTING: Multidisciplinary, neonatal-pediatric intensive care unit of a
      university teaching hospital. METHODS: Descriptive study of infants and children
      <or=16 yrs of age with acute respiratory failure requiring assisted ventilation.
      During 2002-2003, patients with hypoxemic or hyper-carbic respiratory failure,
      signs of respiratory distress, and described by the attending critical care
      physician as likely to require intubation, were eligible to receive mask
      ventilation as an alternative means of respiratory support. Patients were not
      selected for their underlying disease contributing to the respiratory problems.
      Depending on whether they failed NIV and had to be intubated, the children were
      assigned to nonresponders or responders groups. The two groups were compared
      regarding physiologic variables prospectively evaluated before NIV and at 1, 8,
      24, and 48 hrs of NIV. RESULTS: A total of 42 patients were included. Their
      median age was 2.45 yrs (range, 0.01-18 yrs). Twenty-one patients required mask
      ventilation only with continuous positive airway pressure and 21 with biphasic
      positive airway pressure. In both responders' and nonresponders' blood gas
      results, heart rate and respiratory rate improved significantly after initiation
      of NIV (p<.0001). The courses of these variables did not differentiate between
      the two groups. The overall success rate of NIV was 57%. After 1 hr of NIV, there
      was a significantly higher Fio2 in patients who failed NIV than in responders. An
      Fio2 of >80% after 1 hr of NIV predicted nonresponse with a sensitivity of 56%,
      specificity of 83%, and positive and negative predictive value of 71%.
      CONCLUSION: NIV can be successfully applied to infants and children with acute
      respiratory failure in the setting of a pediatric intensive care unit. The level
      of Fio2 after 1 hr of NIV may be a predictive factor for the treatment success.

PMID- 16276331
TI  - Hemodynamic effects of rescue protocol hydrocortisone in neonates with low
      cardiac output syndrome after cardiac surgery.
AB  - OBJECTIVE: To assess the hemodynamic effects and safety of hydrocortisone in
      neonates with low cardiac output syndrome requiring high levels of inotropic
      support and fluid resuscitation after cardiac surgery. DESIGN: Retrospective
      chart review. SETTING: Fifteen-bed pediatric cardiovascular intensive care unit.
      PATIENTS: Twelve neonates with low cardiac output syndrome after cardiac surgery
      to whom hydrocortisone was administered according to one of two dosing regimens
      (100 mg/[m.day] for 2 days, 50 mg/[m.day] for 2 days, and 25 mg/[m.day] for 1 day
      or 100 mg/[m.day] for 1 day, 50 mg/[m.day] for 2 days, and 25 mg/[m.day] for 2
      days) were identified from the Department of Pharmacy database between September
      2002 and January 2004. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The
      mean and systolic blood pressure increased significantly 3 hrs after
      hydrocortisone treatment from the values preceding hydrocortisone administration.
      The mean blood pressure increased from 44.0+/-3.0 to 55.4+/-2.3 mm Hg (p=.01) and
      the systolic blood pressure increased from 64.2+/-4.7 to 78.3+/-3.4 mm Hg
      (p=.04). Comparable beneficial changes were also seen in the heart rate, which
      decreased from 168.3+/-4.6 to 148.3+/-5.6 beats/min (p=.004) after 24 hrs of
      hydrocortisone administration and remained at this level during the 72 hrs of
      follow-up. Significant weaning of epinephrine infusions was possible, from a mean
      dose of 0.16 to 0.06 microg/(kg.min) (p=.008), within 24 hrs after the initiation
      of steroid administration, and this reduction was not offset by increases in
      other inotropic agents. hydrocortisone administration caused nonsignificant
      increases in mean blood glucose concentration (from 116.2+/-20.6 to 156.0+/-25.6
      mg/dL; p=.64), mean white blood cell count (from 16.6+/-1.6 to 18.9+/-2.6 x 10
      U/L; p=.35), and sodium level (from 144.7+/-1.3 to 145.3+/-1.3 mmol/L; p=.51).
      Ten of the 12 patients (83.3%) survived. CONCLUSION: Most of the hemodynamically
      compromised neonates who were unresponsive to high doses of inotropic agents and
      fluid resuscitation after heart surgery responded to hydrocortisone with
      improvement of hemodynamic parameters and a decrease in inotropic requirements.

PMID- 16276333
TI  - Leadership and management training of pediatric intensivists: how do we gain our
      skills?
AB  - BACKGROUND: Intensivists manage a diverse team of health care professionals. For
      decades, business literature has recognized the value of leadership and
      management skills, yet this is relatively unexplored in critical care. OBJECTIVE:
      Investigate the status of intensivists' preparation for the clinical leadership
      and management roles that they will assume after medical training. DESIGN:
      Authoritative business leadership literature was reviewed to identify attributes
      of successful leadership and management relevant to critical care. A survey was
      designed to assess the process by which intensivists learn these attributes and
      to assess their perceived level of preparedness (20 items). Each survey item
      received a preparedness score structured as a Likert scale (1=not prepared,
      5=very prepared), representing the averaged response to each item. In addition,
      an inadequate preparedness percentage was created representing the percentage of
      respondents answering "not at all prepared" and "hardly prepared" on the Likert
      scaled items. SETTING: Pediatric Critical Care Medicine Board Review Course,
      Washington, DC, 2004. SUBJECTS: Physician course participants (n=259).
      INTERVENTION: Survey administration. MEASUREMENTS AND MAIN RESULTS: The response
      rate was 61% (n = 159). The majority of respondents (69%) had completed
      fellowship training (median, 1 yr posttraining). Modeling the behavior of other
      physicians was the dominant technique for leadership and management skill
      acquisition (86%). The respondents were taught these skills by a variety of
      sources (attendings, 92%; other fellows, 42%; nurses, 37%; teachers, 20%;
      residents, 14%). Most (82%) thought that leadership and management training was
      important or very important, yet only 47% had received any formal training (40%
      fellowship, 36% residency, 21% medical school, 16% masters, 30% other). Overall,
      respondents felt only "somewhat prepared" for the 20 leadership and management
      items surveyed (mean+/- sd of preparedness score, 2.8+/- 0.2). Respondents were
      least prepared to manage conflict within a team, manage conflict with other
      groups, and manage stress effectively (preparedness scores of 2.5, 2.4, and 2.6
      and inadequate preparedness percentages of 19.5%, 15.7%, and 18.9%,
      respectively). Respondents were most prepared to "set high standards"
      (preparedness score=3.3). Of the respondents feeling at least somewhat prepared,
      only 33% credited medical training as preparing them. CONCLUSIONS: Although
      leadership and management training was perceived as important to this sample of
      pediatric generally young intensivists, most feel inadequately prepared for
      critical aspects of these responsibilities, most notably, stress and conflict
      management. These findings provide an opportunity for specific curriculum
      development in leadership and management for those believing these skills should
      be further refined.

PMID- 16276334
TI  - Evaluation of tissue saturation as a noninvasive measure of mixed venous
      saturation in children.
AB  - BACKGROUND: Mixed venous saturation (S & OV0456;o2) is an important measurement
      that helps guide the care of critically ill patients. Invasive S & OV0456;o2
      assessment in infants and children is often avoided because of the inherent
      risks. A noninvasive tissue saturation (S to 2) monitor has recently been
      developed that uses near-infrared spectroscopy to measure oxyhemoglobin
      saturation in muscle. In adult and animal studies, S to 2 correlated with oxygen
      delivery and S & OV0456;o2. There has been no evaluation in pediatric patients.
      OBJECTIVE: To evaluate tissue saturation as a noninvasive measure of mixed venous
      saturation in children. DESIGN: A prospective observational study. SETTING:
      Catheterization laboratory in a tertiary care children's medical center.
      PATIENTS: We studied 98 children (49 without intracardiac mixing and 49 with
      intracardiac mixing) <or=12 yrs of age who underwent cardiac catheterization.
      Under general anesthesia, we compared S to 2 measured over the deltoid muscle
      with superior vena cava saturation in both groups and S to 2 with pulmonary
      artery saturation in patients without intracardiac mixing. Paired measurements
      were analyzed for bias, precision, and correlation via Bland-Altman plot and
      linear regression. RESULTS: No meaningful correlation was found between S to 2
      and superior vena cava saturation or pulmonary artery saturation. Bland-Altman
      analyses of S to 2 with superior vena cava saturation yielded bias values of 
      6.67 +/- 37.33% in patients with intracardiac mixing and -0.82 +/- 41.31% in
      patients without mixing. Bland-Altman analysis of S to 2 with pulmonary artery
      saturation yielded a bias of 3.61 +/- 41.32% in patients without mixing.
      Differences between noninvasive and invasive measurements were greatest in
      smaller children. CONCLUSION: Noninvasive tissue saturation over the deltoid does
      not correlate with S & OV0456;o2 in children. It is possible that more precise
      probe spacing, coupled with optimal muscle-mass location, could result in more
      accurate measures in future investigations.

PMID- 16276335
TI  - Early treatment of acute stress disorder in children with major burn injury.
AB  - OBJECTIVE: This study examines retrospectively the response rate of pediatric
      burn survivors with acute stress disorder to either imipramine or fluoxetine.
      METHODS: On retrospective chart review, 128 intensive care unit patients (85
      boys, 43 girls) with 52%+/- 20% total body surface area burn, length of stay of
      32.8+/- 25.2 days, mean age of 9.1+/- 4.7 yrs, and age range of 13 months to 19
      yrs met criteria for acute stress disorder after >or=2 days of symptoms and were
      treated with either imipramine or fluoxetine. If significant improvement did not
      occur within 7 days, the medication was either increased or switched to the other
      class. RESULTS: Initially, 104 patients were treated with imipramine and 24 with
      fluoxetine. A total of 84 patients responded to imipramine: seven of these
      patients required a higher dose. A total of 18 patients responded to initial
      fluoxetine treatment. Of 26 nonresponders to the initial medication, 13
      imipramine failures and one fluoxetine failure refused further treatment. The
      other 12 responded to the second medication. Therefore, 114 of 128 treated
      patients (89%) responded to either fluoxetine (mean dose, 0.30+/- 0.14 mg/kg) or
      imipramine (mean dose, 1.30+/- 0.55 mg/kg). Response was independent of sex and
      age but was less for those with burns of >60% total body surface area. The side
      effects of each medication were not significant. Most patients continued
      treatment for >or=3 months; some required 6 months of treatment before successful
      discontinuation. CONCLUSIONS: Early treatment of acute stress disorder with
      either imipramine or fluoxetine is often able to reduce its symptoms. This is a
      review of a single hospital's experience in managing psychiatric distress in this
      very high-risk group of burned children. Additional clinical studies are needed
      before generalizing these findings.

PMID- 16276336
TI  - Increased levels of tumor necrosis factor-alpha and decreased levels of
      interleukin-12 p 70 in tracheal aspirates, within 2 hrs after birth, are
      associated with mortality among ventilated preterm infants.
AB  - OBJECTIVE: To determine the association of antibacterial interleukin (IL)-12 p 70
      levels as well as the pathogen-induced proinflammatory cytokine response in
      tracheal aspirate (TA) to respiratory failure and mortality among ventilated
      preterm infants. DESIGN: A prospective observational clinical cohort study with
      measurements of cytokine levels and microbial cultures of TA from ventilated
      preterm neonates. Interleukin (IL)-1 beta, IL-8, IL-6, IL-10, IL-12 p 70, and
      tumor necrosis factor (TNF)-alpha were measured in TA within 2 hrs of birth, and
      comorbidity characteristics were recorded prospectively. The association between
      cytokine levels in TA and neonatal mortality was determined, with correction for
      comorbidity factors by means of multivariate stepwise logistic regression.
      SETTING: A single tertiary neonatal intensive care unit at the University
      Hospital of Antwerp, Belgium. PATIENTS: One hundred forty-one neonates born
      before a gestational age of 31 wks and who required ventilation were enrolled in
      the study; 31 (22%) died and 37 (26%) had airway colonization. MEASUREMENTS AND
      MAIN RESULTS: The airway colonization rate was significantly greater among
      deceased neonates (45% vs. 21%; chi-square, 7.4; p=.007). Neonates who died had a
      significantly lower IL-12 p 70 cytokine level (6 pg/mL vs. 11 pg/mL; p<.05) in
      their TA. Neonates with a low IL-12 p 70 cytokine level had more pronounced
      respiratory failure (significantly higher oxygenation index, higher degree of
      radiologic respiratory distress syndrome, higher critical index for babies score,
      and more surfactant use). Multivariate analysis revealed that, after correction
      for severity of disease by critical index for babies score, the degree of
      intraventricular hemorrhage (odds ratio, 5.0 [95% confidence interval, 2.6-9.7]),
      low IL-12 p 70 levels (odds ratio, 4.9 [95% confidence interval, 2.1-11.7]), and
      high TNF-alpha levels in TA (odds ratio, 3.5 [95% confidence interval, 1.6-7.5])
      were significantly associated with neonatal mortality. CONCLUSIONS: Pathogen
      induced excessive production of the proinflammatory cytokine TNF-alpha and lack
      of antibacterial IL-12 p 70 response in the TA are associated with increased
      neonatal mortality among ventilated preterm infants.

PMID- 16276337
TI  - Effect of low-bias flow oscillation with partial liquid ventilation on
      fluoroscopic image analysis, gas exchange, and lung injury.
AB  - OBJECTIVE: To evaluate the effect of low-bias flow oscillation (LBFO) with
      partial liquid ventilation (PLV) on perfluorochemical evaporation,
      histopathology, and oxidative tissue damage in an animal model of acute lung
      injury. DESIGN: Prospective, randomized animal study. SETTING: Research
      laboratory of a health sciences university. SUBJECTS: Twelve New Zealand White
      rabbits. INTERVENTIONS: Juvenile rabbits were anesthetized, paralyzed, and
      ventilated through a tracheostomy with either high-frequency oscillatory
      ventilation or LBFO. Lung injury was induced by repeated saline lavage, after
      which perflubron was instilled through a side port of the endotracheal tube.
      Lateral fluoroscopic images were performed at baseline and at various postfill
      intervals of animals in the high-frequency oscillatory ventilation-PLV and LBFO
      PLV groups. The images were digitalized for computer analysis of the Lung Lucency
      Index, a surrogate marker of perflubron evaporation. Histopathologic evaluation
      was performed using a lung-injury scoring system. Malondialdehyde was measured in
      lung homogenates to assess oxidative damage. MEASUREMENTS AND MAIN RESULTS: There
      were no significant differences in gas exchange and ventilator settings between
      groups throughout the experiment. At 300 mins, the high-frequency oscillatory
      ventilation-PLV group had a significantly higher Lung Lucency Index compared with
      the LBFO-PLV group in both dependent and nondependent lung regions (a high Lung
      Lucency Index correlates with increased perflubron loss). Malondialdehyde
      measurements were not different between groups. Animals treated with LBFO-PLV had
      a lower histopathologic lung-injury score compared with high-frequency
      oscillatory ventilation-PLV. CONCLUSION: LBFO-PLV is a viable mode of ventilation
      in a model of acute lung injury and is associated with significant preservation
      of perflubron in comparison with high-frequency oscillatory ventilation-PLV. The
      lower evaporative losses during LBFO-PLV were associated with improved histology
      scores.

PMID- 16276338
TI  - Recombinant human Clara cell secretory protein in acute lung injury of the
      rabbit: effect of route of administration.
AB  - OBJECTIVE: To test the hypothesis that intratracheal instillation of Clara cell
      secretory protein (CC 10) to the lung may afford greater protection than
      intravenous administration from ventilator-induced lung inflammation. DESIGN:
      Interventional laboratory study. SETTING: An academic medical research facility
      in northeastern United States. SUBJECTS: Sedated, lavage-injured juvenile
      rabbits. INTERVENTIONS: A total of 18 juvenile rabbits were anesthetized,
      ventilated, injured with saline lavage (Pao2 of <100 mm Hg; respiratory
      compliance of <0.50 mL.cm H2O.kg and <50% baseline), and randomized to receive
      intratracheally administered surfactant plus no recombinant human CC 10 (rhCC 10,
      control), intravenous rhCC 10, or intratracheal rhCC 10. MEASUREMENT AND MAIN
      RESULTS: Arterial blood chemistry and pulmonary mechanics were monitored; plasma
      and urine were collected serially. After 4 hrs of ventilation, lungs were lavaged
      and harvested. Surfactant function was analyzed from bronchoalveolar lavage
      samples (surfactometry); rhCC 10, interleukin-8, and lung myeloperoxidase
      concentrations were measured. Pao2, oxygenation index, ventilatory efficiency
      index, and respiratory compliance were not different across time or group beyond
      injury. Surfactometry data identified no differences as a function of group or
      time. Plasma, bronchoalveolar lavage, and lung interleukin-8 concentrations, lung
      myeloperoxidase concentrations, and inflammatory cell counts in the alveolar and
      interstitial spaces of intravenous and intratracheal groups were lower than in
      the control group (p < .05) but not statistically different from each other.
      Concentrations of rhCC 10 in lung, bronchoalveolar lavage, and plasma were
      greater in the intratracheal group than in the intravenous group (p<.05). Urine
      rhCC 10 concentrations were greater for the intravenous group than for the
      intratracheal group (p<.05) at 1, 3, and 4 hrs after treatment. No group
      differences in histomorphometry were noted. CONCLUSIONS: Both intravenous and
      intratracheal rhCC 10 delivery, after surfactant therapy, effectively decrease
      lung inflammation vs. surfactant alone. While supporting the physiologic profile,
      intratracheal instillation results in greater, maintained lung and plasma rhCC 10
      pools compared with intravenous administration. As such, intratracheal
      instillation of rhCC 10 may afford more prolonged protection against lung
      inflammation than intravenous administration.

PMID- 16276339
TI  - Posttransfusion equilibration of hematocrit in hemodynamically stable neonates.
AB  - OBJECTIVE: To determine whether hematocrit obtained 15 mins after blood
      transfusion in hemodynamically stable neonates is significantly different from
      that obtained after 6 hrs. We hypothesized that the hematocrit stabilizes within
      the first 15 mins that follow a 3-hr blood transfusion in preterm infants.
      DESIGN: We prospectively studied 24 consecutive infants who received blood
      transfusion. Hematocrit was measured immediately before the transfusion and 15
      mins and 6 hrs after the transfusion of 10 mL/kg body weight of sedimented red
      blood cells administered over 3 hrs. Hematocrit was measured by centrifugation of
      a capillary. RESULTS: There was a significant increase in hematocrit from
      pretransfusion values both at 15 mins and 6 hrs. The increase in hematocrit from
      the pretransfusion value was identical (11%) at both 15 mins and 6 hrs.
      CONCLUSION: The hematocrit obtained 15 mins after the end of a 3-hr blood
      transfusion in hemodynamically stable, anemic infants is indistinguishable from
      that obtained after 6 hrs in the same infants. Thus, if the increase of
      hematocrit is deemed insufficient at 15 mins after the transfusion, it is
      possible to complete the transfusion without exposing the patient to an
      additional donor.

PMID- 16276340
TI  - Survival of candida sepsis in extracorporeal membrane oxygenation.
AB  - OBJECTIVE: To report the survival of fungal sepsis in extracorporeal membrane
      oxygenation. DESIGN: Single case report. SETTING: Tertiary referral children's
      hospital pediatric intensive care unit. PATIENTS: A single case report of an
      infant with congenital heart disease who developed candida sepsis while supported
      postoperatively with extracorporeal membrane oxygenation. RESULTS: This infant
      survived a prolonged episode of candidemia after repair of congenital heart
      disease, which required extracorporeal membrane oxygenation support. The patient
      has no identified sequelae at 6-month follow-up and continues on long-term
      fluconazole therapy for candida endocarditis. CONCLUSIONS: Candidemia,
      particularly Candida albicans species, may not be a contraindication for
      extracorporeal membrane oxygenation support. With antifungal therapy and adequate
      inotropic use to counter the effects of septicemia, survival can be maintained
      until the patient adequately recovers, allowing decannulation, removal of all
      catheters, and eventual bloodstream sterility.

PMID- 16276341
TI  - The patient died, but we can try again: simulation in pediatric critical care
      training.

PMID- 16276342
TI  - Fluid management during respiratory failure: "whatever?".

PMID- 16276343
TI  - Monitoring the depth of sedation in the pediatric ICU patient: where are we, or
      more importantly, where are our patients?.

PMID- 16276347
TI  - Enhanced suppression of tumor growth using a combination of NK4 plasmid DNA-PEG
      engrafted cationized dextran complex and ultrasound irradiation.
AB  - This investigation aims to determine experimentally whether or not ultrasound
      (US) irradiation is effective in enhancing the in vivo gene expression of NK4
      plasmid DNA and suppressing tumor growth. NK4, composed of the NH2-terminal
      hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF),
      acts as an HGF-antagonist and angiogenesis inhibitor. Dextran was cationized by
      introducing spermine to the hydroxyl groups to allow for polyionic complexation
      with NK4 plasmid DNA. The cationized dextran was additionally modified with
      poly(ethylene glycol) (PEG) molecules giving PEG engrafted cationized dextran.
      Significant suppression of tumor growth was observed when PEG engrafted
      cationized dextran-NK4 plasmid DNA complexes were intravenously injected into
      mice carrying a subcutaneous Lewis lung carcinoma tumor mass with subsequent US
      irradiation when compared with the cationized dextran-NK4 plasmid DNA complex and
      naked NK4 plasmid DNA with or without US irradiation. We conclude that
      complexation with PEG-engrafted cationized dextran in combination with US
      irradiation is a promising way to target the NK4 plasmid DNA to the tumor for
      gene expression.

PMID- 16276348
TI  - PCTAIRE3: a putative mediator of growth arrest and death induced by CTS-1, a
      dominant-positive p53-derived synthetic tumor suppressor, in human malignant
      glioma cells.
AB  - Chimeric tumor suppressor-1 (CTS-1) is based on the sequence of p53 and was
      designed as a therapeutic tool resisting various mechanisms of p53 inactivation.
      We previously reported that an adenovirus expressing CTS-1 (Ad-CTS-1) has
      superior cell death-inducing activity in glioma cells compared with wild-type
      p53. Here, we used cDNA microarrays to detect changes in gene expression
      preferentially induced by Ad-CTS-1. The putative serine threonine kinase,
      PCTAIRE3, and the quinone oxireductase, PIG3, were strongly induced by Ad-CTS-1
      compared with wild-type p53. An adenoviral vector encoding PCTAIRE3 (Ad-PCTAIRE3)
      induced growth arrest and killed a minor proportion of the glioma cells. Ad-PIG3
      alone affected neither growth nor viability. However, coinfection with Ad
      PCTAIRE3 and Ad-PIG3 resulted in enhanced growth inhibition compared with Ad
      PCTAIRE3 infection alone. Ad-CTS1, Ad-PCTAIRE3 or Ad-PIG3 induced the formation
      of free reactive oxygen species (ROS). However, the prevention of ROS formation
      induced by Ad-PCTAIRE3 and Ad-CTS-1 did not block growth arrest and cell death,
      suggesting that ROS formation is not essential for these effects. Altogether,
      these data identify PCTAIRE3 as one novel growth-inhibitory and death-inducing
      p53 response gene and suggest that changes in the expression of specific target
      genes contribute to the superior anti-glioma activity of CTS-1.

PMID- 16276349
TI  - Immune responses against PSMA after gene-based vaccination for immunotherapy-A:
      results from immunizations in animals.
AB  - Two plasmid DNA vaccines, encoding either products that are retained in the
      cytosol and degraded in the proteasome (tVacs; hPSMAt), or secreted proteins
      (sVacs; hPSMAs) were evaluated for stimulation of cytotoxic cell or antibody
      responses. Immunization with both vectors led to generation of cell cytotoxicity
      providing granulocyte-macrophage colony-stimulating factor was administered with
      the vaccine. Spleen cells from animals immunized with hPSMAt demonstrated
      stronger cytotoxicity to the target cells. Priming with a vector that encoded a
      xenogeneic protein (hPSMAt; 'xenogeneic' construct) and boosting with a vector
      that encoded an autologous protein (rPSMAt; 'autologous' construct) gave the best
      protection against tumor challenge. Immunization with tVacs did not lead to
      formation of antibodies to the target protein as detected by Western blot or
      ELISA, while immunization with sVacs or with the protein did. Antibodies were of
      mixed Th1-Th2 isotype. Priming with tVacs and boosting with protein also resulted
      in antibody formation, but in this case the antibodies were from the cytotoxic,
      Th1 isotype. The best strategy to obtain a strong cellular cytotoxic response,
      therefore, seems to be gene-based vaccinations with tVacs, priming with the
      'xenogeneic' and boosting with the 'autologous' constructs. When cytotoxic
      antibody production is the goal, priming should be performed with the tVacs while
      boosting with the protein.

PMID- 16276350
TI  - Bone mineral density changes on androgen deprivation therapy for prostate cancer
      and response to antiresorptive therapy.
AB  - Androgen deprivation therapy improves survival of patients with prostate cancer
      and leads to hypogonadal state. Gonadal hormones are essential for skeletal
      integrity and hypogonadism constitutes a major risk factor for osteoporosis. To
      examine the bone loss secondary to androgen deprivation therapy, we reviewed the
      bone mineral density (BMD) studies of 152 patients with prostate cancer with mean
      duration of androgen deprivation therapy of 58 months. Among them 55 subjects had
      follow-up BMD measurement at 12-15 months with 39 of them on antiresorptive
      therapy. Osteoporosis was noted at least at one site in 92 (60.5%), among which
      74 (48.7%) had changes at hip with the more prominent changes at ward's triangle,
      18 (11.8%) at other sites. Osteopenia was present in 37 (24%) and only 17 (11%)
      were normal. The duration of antiandrogen therapy did not correlate with the
      degree of bone loss. Significant in improvement in the BMD is noted at 12-15
      month follow-up on antiresorptive therapy. We conclude that men treated with
      androgen deprivation therapy are at risk for bone loss and should have BMD
      measured at the time of initiation of androgen deprivation therapy and
      periodically.

PMID- 16276351
TI  - Brn-3a neuronal transcription factor functional expression in human prostate
      cancer.
AB  - Neuroendocrine differentiation has been associated with prostate cancer (CaP).
      Brn-3a (short isoform) and Brn-3c, transcriptional controllers of neuronal
      differentiation, were readily detectable in human CaP both in vitro and in vivo.
      Brn-3a expression, but not Brn-3c, was significantly upregulated in >50% of
      tumours. Furthermore, overexpression of this transcription factor in vitro (i)
      potentiated CaP cell growth and (ii) regulated the expression of a neuronal gene,
      the Nav1.7 sodium channel, concomitantly upregulated in human CaP, in an isoform
      specific manner. It is concluded that targeting Brn-3a could be a useful strategy
      for controlling the expression of multiple genes that promote CaP.

PMID- 16276352
TI  - Intermittent androgen replacement for intense hypogonadism symptoms in castrated
      patients.
AB  - OBJECTIVES: For locally advanced prostate cancer management, medical androgen
      deprivation and surgical castration are alternatives. These hormonal treatments
      may cause a myriad of side effects, such as osteoporosis with increased risk of
      fractures, anemia, behavioral changes and lack of sexual interest. We evaluated
      the feasibility of intermittent androgen replacement in surgically castrated
      patients with significant side effects. METHODS: Five patients with advanced
      prostate cancer, ranging from 71 to 77 years of age (mean age = 74 years),
      surgically castrated for at least 3 years, with important symptoms of
      hypoandrogenism received testosterone replacement. They were followed with PSA
      and testosterone measurement every other month and bone scans every 6 months.
      RESULTS: For the first year all patients improved significantly, none of them
      showed PSA increase over 10 ng/ml. There was no evidence of local recurrence or
      distant disease. After 18 months, only one patient (20%) had a significant PSA
      increase, controlled by androgen withdrawal. No side effects or metastasis were
      observed. CONCLUSIONS: Hormonal replacement in patients that underwent castration
      seems to be feasible in improving intense symptoms associated to androgen
      deprivation. After 18 months, no evidence of recurrence was noted. It is an
      experimental alternative for highly symptomatic patients, but the short follow-up
      and the small number of patients cannot allow for definitive conclusions and
      should be studied further.

PMID- 16276353
TI  - p21WAF1/CIP1 gene is inactivated in metastatic prostatic cancer cell lines by
      promoter methylation.
AB  - INTRODUCTION: p21WAF1/CIP1 may act as a tumour suppressor gene (TSG) and loss of
      the p21WAF1/CIP1 gene has been reported in several solid tumours. The aim of this
      study was to see whether p21WAF1/CIP1 was expressed in metastatic prostate cancer
      cell lines and to determine if there was methylation of the p21WAF1/CIP1
      promoter. METHOD: PC3, LNCaP and DU145 metastatic prostate cancer cell lines,
      1542NP normal prostate, and RD rhabdomyosarcoma cell lines were cultured in the
      demethylating agent 5-Aza-2 deoxycytidine (5-Aza-CdR). p21WAF1/CIP1 mRNA
      expression was analysed by RT-PCR. DNA from untreated cell lines was modified
      with sodium bisulphite and promoter sequencing was performed. RESULTS:
      p21WAF1/CIP1 was expressed at low or undetectable levels in metastatic prostate
      cancer cell lines but expression was reactivated by treatment with 5-Aza-CdR.
      Sequence analysis of the promoter region revealed several sites of methylation at
      the 5' end of a CpG island in the PC3, LNCaP and DU145 cell line DNA but not in
      the normal prostate control DNA. Most notably the Sis-inducible element (SEI)-1-a
      STAT1-binding site, was methylated. CONCLUSIONS: In this study, we show that
      p21WAF1/CIP1 expression in metastatic prostate cancer cell lines is enhanced as a
      result of demethylation of the DNA. Furthermore, several cytosine residues in the
      promoter region are methylated, including critical binding sites. The inhibition
      of the STAT1-signalling pathway by methylation of the promoter may inactivate the
      p21WAF1/CIP1 TSG in prostate cancer.

PMID- 16276354
TI  - Subcortical face processing.
AB  - Recent functional imaging, neuropsychological and electrophysiological studies on
      adults have provided evidence for a fast, low-spatial-frequency, subcortical face
      detection pathway that modulates the responses of certain cortical areas to faces
      and other social stimuli. These findings shed light on an older literature on the
      face-detection abilities of newborn infants, and the hypothesis that these
      newborn looking preferences are generated by a subcortical route. Converging
      lines of evidence indicate that the subcortical face route provides a
      developmental foundation for what later becomes the adult cortical 'social brain'
      network, and that disturbances to this pathway might contribute to certain
      developmental disorders.

PMID- 16276355
TI  - Metabotropic glutamate receptors in the basal ganglia motor circuit.
AB  - In recent years there have been tremendous advances in our understanding of the
      circuitry of the basal ganglia and our ability to predict the behavioural effects
      of specific cellular changes in this circuit on voluntary movement. These
      advances, combined with a new understanding of the rich distribution and diverse
      physiological roles of metabotropic glutamate receptors in the basal ganglia,
      indicate that these receptors might have a key role in motor control and raise
      the exciting possibility that they might provide therapeutic targets for the
      treatment of Parkinson's disease and related disorders.

PMID- 16276356
TI  - Opinion: the neural basis of human moral cognition.
AB  - Moral cognitive neuroscience is an emerging field of research that focuses on the
      neural basis of uniquely human forms of social cognition and behaviour. Recent
      functional imaging and clinical evidence indicates that a remarkably consistent
      network of brain regions is involved in moral cognition. These findings are
      fostering new interpretations of social behavioural impairments in patients with
      brain dysfunction, and require new approaches to enable us to understand the
      complex links between individuals and society. Here, we propose a cognitive
      neuroscience view of how cultural and context-dependent knowledge, semantic
      social knowledge and motivational states can be integrated to explain complex
      aspects of human moral cognition.

PMID- 16276357
TI  - Opinion: an integrated approach to classifying neuronal phenotypes.
AB  - Characterizing the functional phenotypes of neurons is essential for
      understanding how genotypes can be related to the neural basis of behaviour.
      Traditional classifications of neurons by single features (such as morphology or
      firing behaviour) are increasingly inadequate for reflecting functional
      phenotypes, as they do not integrate functions across different neuronal types.
      Here, we describe a set of rules for identifying and predicting functional
      phenotypes that combine morphology, intrinsic ion channel species and their
      distributions in dendrites, and functional properties. This more comprehensive
      neuronal classification should be an improvement on traditional classifications
      for relating genotype to functional phenotype.

PMID- 16276358
TI  - Obesity in Canada: where and how many?
AB  - CONTEXT: Obesity rates are rising sharply among all industrialized countries; the
      situation seems to be worse in English speaking countries. Taking into account
      genetic predisposition, excess of caloric intake combined with low energy
      expenditure will usually result in obesity. OBJECTIVES: To describe and compare
      regional obesity rates across Canada and assess the ecological relationship
      between regional rates of obesity, low level of leisure-time physical activity,
      and low fruit and vegetable consumption. DESIGN: Cross-sectional population-based
      analysis from the 2003 Canadian Community Health Survey. MEASURES AND DATA
      ANALYSES: Canadian population distributions of body mass index (BMI), leisure
      time physical activity and daily fruit and vegetable consumption were obtained
      from Statistics Canada. All these measures were based on the respondent's self
      reported answers to a computer-assisted personal or telephone interview. Obesity
      rates (BMI> or =30), rates of low level of leisure-time physical activity (less
      than 1.5 kcal of energy expenditure per day), and rates of low fruit and
      vegetable consumption (less than five times a day) for the 106 Canadian Health
      regions were mapped to illustrate their geographical distribution. Cartograms
      were used in addition to traditional mapping to take into account the differences
      in population density between these small areas. RESULTS: In 2003, 15.2% of
      Canadian individuals aged 20 years and older were considered obese. The rates of
      obesity varied substantially between the 106 Canadian health regions: from 6.2%
      in Vancouver to 47.5% in aboriginal population area. At the health region level,
      low leisure-time physical activity and low fruit and vegetable consumption are
      both good predictors of obesity (odds ratio of 9.2 and positive predictive value
      of 93% when considered simultaneously). CONCLUSION: There is a strong gradient in
      obesity prevalence between Canadian health regions. At the regional level, high
      rates of low level of physical activity, and high rates of low fruit and
      vegetable consumption were both found good predictors of high rates of obesity.

PMID- 16276359
TI  - Health Hunters--an intervention to prevent overweight and obesity in young high
      risk women.
AB  - AIM: The aim of the study was to develop and implement an obesity and weight gain
      prevention program targeted to a high-risk group. METHOD: Women, 18-28 years old,
      with at least one severely obese parent, were randomized to the intervention or
      control group of the 'Health Hunters' program. During 1 year of follow-up, the
      intervention group received an individualized behavioral program focusing on food
      choice, physical activity and other lifestyle factors. Anthropometric measures,
      DXA-based body composition and fitness levels were measured at baseline and after
      1 year. Self-reported changes in obesity-related behaviors were also assessed.
      RESULTS: Baseline examinations were conducted in 40 women, of whom 30 completed
      follow-up examinations 1 year later. Pregnancy was the most common reason for
      failure to complete the study. Compared to the control group (which gained
      weight), the intervention group displayed significant improvements in body
      weight, body mass index, waist circumference, waist-to-hip ratio and self
      reported physical activity. Changes in body composition, although not
      significant, suggested that the intervention tended to be associated with
      improved body composition. Further analysis of changes in diet and fitness in
      relation to concurrent weight changes indicated that the strongest 'protective'
      associations were for energy percent protein, fiber density and fitness.
      CONCLUSION: Pilot data from the Health Hunters obesity prevention program
      indicates that it is effective in high-risk young women with familial
      predisposition for obesity.

PMID- 16276360
TI  - Validation of a brief, reliable scale to measure knowledge about the health risks
      associated with obesity.
AB  - BACKGROUND: Obesity represents a serious threat to health through its association
      with conditions such as type 2 diabetes mellitus, coronary heart disease and
      certain types of cancer. Knowledge regarding risk to health is an important
      determinant of behaviour and is the focus of many health education strategies. To
      the authors' knowledge, there is no valid and reliable measure of knowledge
      regarding the health risks associated with obesity. AIM: To validate a short,
      reliable psychometric scale measuring knowledge regarding the effects of obesity
      on health, the Obesity Risk Knowledge (ORK-10) scale. METHODS: The ORK-10 scale
      was administered to a sample of individuals with no specific obesity-related
      expertise (n=230) and a sample of experts (n=200). Univariate and multivariate
      statistical analyses were used to investigate the scale's criterion validity.
      RESULTS: The ORK-10 scale has good internal consistency (Cronbach's alpha
      coefficient>0.7) and is acceptable for use in a UK adult population with an
      estimated reading age of 12-13 years. The scale demonstrated strong criterion
      validity, as those with educational or vocational expertise in the field of
      obesity achieved significantly higher scores than nonexperts (median 9.0 vs 4.0,
      Z=-17.364; P<0.001). This relationship was maintained after controlling for the
      potentially confounding factors of age and level of education. Nonexperts
      demonstrated low levels of knowledge regarding the health risks associated with
      obesity. CONCLUSIONS: The ORK-10 scale meets standard psychometric criteria for
      reliability and validity. This scale could be used to assess the effectiveness of
      health education interventions, to target the provision of health information and
      to investigate the interaction between knowledge and obesity-related behaviour.

PMID- 16276361
TI  - Lifecourse weight patterns and adult-onset diabetes: the Glasgow Alumni and
      British Women's Heart and Health studies.
AB  - OBJECTIVE: To examine the association between body weight measures across the
      lifecourse and the risk of adult-onset diabetes. METHODS: We analysed data from
      the Glasgow Alumni Cohort and the British Women's Heart and Health Study (BWHHS).
      The former included 5,571 men and women who had height and weight measured at
      university, and reported birthweight, mid- and later-life weight in a postal
      questionnaire. The BWHHS analysis included 4,280 women who had height and weight
      measured in later adulthood and recalled their birthweight and early adult height
      and weight. Adult-onset diabetes was defined as doctor-diagnosed disease after
      age 30, either self-reported or abstracted from medical records. RESULTS: Thirty
      nine women and 209 men (Glasgow Alumni study) and 314 women (BWHHS) had diabetes.
      Those with diabetes had lower mean birthweight than those without, although the
      differences were small. Individuals with diabetes were also shorter and heavier
      at all ages than those without diabetes. Being overweight during at least one
      time period in adult life was associated with an increased risk of diabetes,
      compared to those who were never overweight. While there was no age at which
      being overweight was particularly detrimental, the risk associated with being
      overweight was cumulative across the lifecourse. CONCLUSIONS: Being overweight at
      any point during life is associated with an increased risk of adult-onset
      diabetes. The cumulative nature of this association reinforces the need to
      prevent the development of excess weight at an early age to reduce diabetes
      prevalence in coming decades.

PMID- 16276362
TI  - Breastfeeding and overweight in childhood: evidence from the Pelotas 1993 birth
      cohort study.
AB  - OBJECTIVES: The effect of breastfeeding duration on the prevalence of overweight
      and on mean weight for height z-score (WHZ) was evaluated in Brazilian children.
      DESIGN: Prospective population-based birth cohort study. SUBJECTS: In total,
      1,273 children aged 4 years, corresponding to a follow-up rate of 87.2%.
      MEASUREMENTS: Three explanatory variables were studied: duration of any
      breastfeeding, duration of exclusive or predominant breastfeeding, and ever
      breastfeeding. Weight and height were measured using a digital electronic scale
      and a portable stadiometer. Overweight was defined as WHZ >2 using the National
      Center for Health Statistics reference curve. RESULTS: Overweight prevalence at
      the age of 4 years was 10.2% (95% CI 8.4; 11.8). The lowest prevalence (6.5%) was
      observed among children breastfed for >11 months. Among those breastfed for less
      than 3 months, the prevalence of overweight was approximately 9.5%. Mean WHZ
      ranged from 0.38 among children breastfed for less than 1 month to 0.62 among
      those breastfed for 9-11.9 months. No linear trends were detected in the
      association between breastfeeding and anthropometric indicators. None of the
      three breastfeeding variables was significantly associated with the prevalence of
      overweight or mean WHZ in multivariable analyses. No interactions were detected
      between breastfeeding and the variables sex, birth weight, socioeconomic status,
      skin color and pregestational in body mass index. CONCLUSION: Our results do not
      support the hypothesis that breastfeeding promotion would reduce overweight or
      obesity in this population. Existing evidence on many other benefits of
      breastfeeding for the mother and the child supports its continued promotion,
      protection and support.

PMID- 16276363
TI  - Image quality and diagnostic accuracy of 16-slice multidetector computed
      tomography for the detection of coronary artery disease in obese patients.
AB  - BACKGROUND: Cardiac multislice spiral computed tomography (MSCT) scanners permit
      visualization of the coronary arteries with an overall good sensitivity (sens)
      and specificity (spec). However, in obese patients (pts), who are at higher risk
      to develop coronary artery disease (CAD), image quality of MSCT is supposed to be
      limited. At present, there are no data whether the accuracy of MSCT depends on
      the body mass index (BMI). Thus, we compared the catheter-controlled MSCT results
      from normal weight and obese pts in a cohort of 117 pts with regard to sens,
      spec, positive predictive value (PPV), negative predictive value (NPV) and image
      quality. METHODS AND MATERIAL: In all, 21 normal weight pts (group I: BMI<25,
      64.6+/-11.1 years, number of risk factors 2.1+/-1.1), 60 pts with mild overweight
      (group II: BMI 25-30, 64.6+/-8.9 years, number of risk factors 3.4+/-1.0) and 36
      obese pts (group III: BMI >30, 63.0+/-8.5 years, number of risk factors 3.4+/
      0.9) were examined by MSCT (Sensation 16 Speed 4 D((R)), Siemens, Germany, gantry
      rotation time 375 ms) and invasive coronary angiography. MSCT results were
      compared blinded to the results of the coronary angiography with regard to the
      presence or absence of a significant stenosis (>50%) in a modified AHA 13 segment
      (sgt) model. Image quality was assessed on a qualitative scale between 1 (very
      good) and 5 (insufficient image quality) for each sgt. RESULTS: Sens, spec, PPV
      and NPV were statistically not different in all three groups (I:
      0.88/0.97/0.91/0.96, II: 0.83/0.97/0.88/0.95, III: 0.87/0.99/0.96/0.96). 3 pts
      (group I 1, group II 2) had to be excluded from analysis due to technical
      problems. Group I had significantly less risk factors (P < 0.001) and image
      quality was significantly better than in group II and III (P < 0.05). Group II
      and III did not differ with regard to risk factors or image quality. CONCLUSIONS:
      Overweight and obesity have an impact on MSCT image quality but did not hamper
      the diagnostic accuracy. Thus, MSCT is a noninvasive method to detect or rule out
      CAD also in pts with higher BMI. These retrospective data have to be confirmed in
      larger prospective trials.

PMID- 16276364
TI  - Clinical and genetic associations with hypertriglyceridemic waist in a Canadian
      aboriginal population.
AB  - OBJECTIVES: To determine the prevalence of 'hypertriglyceridemic waist' (HTGW) in
      Oji-Cree, to examine its interaction with hepatic nuclear factor-1alpha (HNF1A)
      in association with type 2 diabetes, and to characterize its putative genetic
      determinants. METHOD: The presence or absence of HTGW was determined in 522 Oji
      Cree subjects (223 males, 299 females), >or=18 years of age, in whom physical
      measurements and fasting plasma analyte concentrations were gathered, and a 75-g
      oral glucose tolerance test was administered, as part of a cross-sectional study.
      Subjects were genotyped for HNF1A codon 319, angiotensinogen (AGT) codons 174 and
      235, G-protein beta3-subunit (GNB3) nucleotide 825, fatty acid-binding protein
      (FABP2) codon 54, nucleotides -455 and -482 of the apolipoprotein (apo) C-III
      (APOC3) promoter, and a 5-bp insertion/deletion polymorphism within the 3'
      untranslated region of protein phosphatase 1 regulatory subunit 3 (PPP1R3).
      RESULTS: The unadjusted prevalence of HTGW in Oji-Cree adults was 20.5%, with
      more males affected than females (27.8 vs 15.1%, P=0.0004). Logistic regression
      analysis, adjusted for age and gender, showed type 2 diabetes was associated with
      both HNF1A G319S (odds ratio (OR) 4.85, 95% CI 2.45, 9.58) and HTGW (OR 4.96, 95%
      CI 2.49, 9.88). When the HNF1A mutation and HTGW were present in combination, the
      OR for type 2 diabetes was markedly increased (OR 43.2, 95% CI 12.4, 150). In
      women only, both GNB3 825C>T and FABP2 A54T genotypes were significantly
      associated with HTGW (OR 2.02, 95% CI 1.01, 4.05 and OR 1.95, 95% CI 1.01, 3.74,
      respectively). CONCLUSIONS: HTGW is prevalent in Oji-Cree, especially in men. The
      ORs for type 2 diabetes were similar ( approximately 5-fold) for subjects with
      either the presence of HTGW or the private HNF1A G319S mutation. These two
      independent risk factors acted synergistically to confer an even greater
      increased risk of type 2 diabetes.

PMID- 16276365
TI  - Neural representations of hunger and satiety in Prader-Willi syndrome.
AB  - OBJECTIVE: To investigate the neural basis of the abnormal eating behaviour in
      Prader-Willi syndrome (PWS), using brain imaging. We predicted that the satiety
      response in those with PWS would be delayed and insensitive to food intake.
      DESIGN AND PARTICIPANTS: The design of this study was based on a previous
      investigation of the neural activation associated with conditions of fasting and
      food intake in a nonobese, non-PWS group. The findings were used to generate
      specific hypotheses regarding brain regions of interest for the current study, in
      which 13 adults with PWS took part (mean +/- s.d. age = 29 +/- 6; BMI = 31.5 +/-
      5.1; IQ = 71 +/- 8, six were female). MEASUREMENTS: Regional cerebral blood flow
      was measured using positron emission tomography in three sessions: one following
      an overnight fast and two following disguised energy controlled meals of similar
      volume and appearance--one of 1674 kJ (400 kcal) and another of 5021 kJ (1200
      kcal). Subjective ratings of hunger, fullness and desire to eat, and blood plasma
      levels of glucose, insulin, leptin, ghrelin and PYY were measured before and
      after each imaging session. RESULTS: The neural representation of hunger, after
      an overnight fast, was similar to that found in nonobese individuals in the
      control study. In contrast, after food intake, the patterns of neural activation
      previously associated with satiety were not found, even after the higher-energy
      load. Lateral and medial orbitofrontal cortical activation was associated with
      consumption of the 400- and 1200-kcal meals, respectively. The medial
      orbitofrontal activation, however, was only found in those who had shown a large
      percentage change in fullness ratings following the higher-energy meal.
      CONCLUSION: We conclude that there is a dysfunction in the satiety system in
      those with PWS. These findings suggest that brain regions associated with satiety
      are insensitive even to high-energy food intake in those with the syndrome. This
      may be the neural basis of the hyperphagia seen in PWS.

PMID- 16276366
TI  - [Influenza--not one, but three diseases].

PMID- 16276367
TI  - [Diagnostic mosaic].

PMID- 16276368
TI  - [Chronic whiplash syndrome].

PMID- 16276369
TI  - [From order to disruption and conflict?].

PMID- 16276370
TI  - [Bed sharing and sudden infant death].
AB  - BACKGROUND: The aim of the study was to investigate bed sharing as a risk factor
      for sudden infant death syndrome (SIDS). MATERIAL AND METHODS: Firstly, SIDS
      cases examined at our institute in two six-year periods before and after the back
      to-sleep campaign (1984-89 and 1998-2003) were investigated. Secondly, a case
      control study was performed, an investigation of variables such as bed sharing,
      parental smoking and breast-feeding in the SIDS group from the latter period
      versus 244 live control infants. RESULTS: The age distribution of the SIDS
      victims in the two periods with high and low SIDS rates differed significantly (p
      = 0.004). In the latter period, fewer SIDS cases were seen in the classical
      distributional peak between the third and the fourth month of life, and a larger
      proportion of SIDS cases were seen within the first month of life. Furthermore, a
      smaller proportion of SIDS victims were found dead in the prone position
      (decrease from 89% to 49%, p < 0.001); and bed sharing at time of death occurred
      more frequently (increase from 7% to 35%, p < 0.001). In the case-control study,
      bed sharing was a significant risk factor for SIDS in infants aged 0-2 months
      (multivariate OR 5.3; 95 % CI 1.3-22, p = 0.02). Bed sharing with a smoking
      mother was associated with a 16-fold increased risk of SIDS (OR 16; 95% CI 2.1 -
      118, p = 0.007). No relationship between bed sharing and SIDS was evident for age
      >2 months. Only 12% of the bed sharing SIDS victims aged <2 months where found in
      the prone position. INTERPRETATION: Bed sharing is associated with an increased
      risk of SIDS for infants <2 months of age. Particularly hazardous is bed sharing
      with a smoking parent.

PMID- 16276371
TI  - [Primary angioplasty in acute ST elevation myocardial infarction in the elderly].
AB  - BACKGROUND: Based on data from the literature, it has been suggested that elderly
      patients with acute myocardial infarction will benefit more from primary
      angioplasty than from thrombolysis. MATERIAL AND METHODS: Data for 100
      consecutive patients, age 75 years or more, presenting with an acute ST elevation
      myocardial infarction (STEMI) without cardiogenic shock and treated with primary
      angioplasty were analysed retrospectively. Some variables were compared with
      previously published data on a group of 100 younger patients (mean age 59) with
      STEMI. RESULTS: Angiographically, the success rate of revascularization was
      similar between the elderly (mean age 80) and the younger STEMI patients.
      Mortality, both at 30 days and at 1 year, was higher among the elderly patients
      compared with the younger (15% vs. 1% and 21% vs. 3% respectively, both p <
      0.001). In the same time period, primary angioplasty was performed in seven
      patients > or = 75 years who presented with cardiogenic shock at admission. All
      of these died during hospitalization. INTERPRETATION: Technically, the success
      rate of primary angioplasty in elderly patients with STEMI was similar to that in
      younger STEMI patients. Mortality after 30 days was significantly higher among
      the elderly patients, but the mortality rate from 30 days to 1 year after the
      infarction was similar to that of the same age group in the general population.
      Patients > or = 75 years presenting with STEMI and cardiogenic shock had no
      benefit of angioplasty; all died during hospitalization.

PMID- 16276372
TI  - [How are patients with acute coronary syndromes treated in Norwegian hospitals?].
AB  - BACKGROUND: Despite recent advances in the understanding and treatment of the
      acute coronary syndromes, the extent to which this progress is applied in
      clinical practice in Norway is uncertain. MATERIAL AND METHODS: We performed a
      nation-wide retrospective survey in 17 Norwegian hospitals to delineate the
      characteristics and treatment of these patients. During the last quarter of 2000,
      data on 913 consecutive patients who were discharged with a diagnosis of acute
      coronary syndrome were analysed. RESULTS: The women (37%) were on average older
      (median 77 years) than the men (median 69 years), they more often had
      hypertension and diabetes mellitus. Men were more frequently treated with statins
      and had a history of smoking. A similar proportion of each gender had acute
      myocardial infarction (68%). Coronary angiography was performed in 338 (37%).
      Medical treatment was similar for both genders, but women were less frequently
      offered angiography (27%) than men (43%), p < 0.001). In multivariate analysis
      the gender difference was significant for the youngest patients. Patients treated
      at community hospitals where less likely to undergo angiography (26%) than
      patients treated at regional hospitals (57%), p < 0.001. INTERPRETATION: This
      survey reveals significant differences in the management of acute coronary
      syndrome patients even in a public health care system. Women and patients treated
      at community hospitals were to a lesser degree offered coronary angiography.

PMID- 16276373
TI  - [PPARgamma agonists--antidiabetics with positive effects on cardiovascular
      risk?].
AB  - INTRODUCTION: Peroxisome proliferator-activated receptor agonists are used as an
      antidiabetic drug with particular effect on insulin sensitivity. MATERIAL AND
      METHODS: This paper is based upon own literature and a Medline search. RESULTS
      AND INTERPRETATION: The drug improves insulin sensitivity, but has several
      cardiovascular effects as well. Blood pressure, serum lipids, endothelial
      function, inflammation and growth of smooth muscle are all modulated by these
      agonists. This group of drugs shows constant antiatherosclerotic properties.
      Larger clinical studies will give the answer whether this treatment can reduce
      micro- and macro-vascular complications in diabetes.

PMID- 16276374
TI  - [Fluid management and the risk of cerebral oedema in children with diabetic
      ketoacidosis].
AB  - BACKGROUND: Cerebral oedema is a rare but life-threatening complication of
      diabetic ketoacidosis in children. MATERIAL AND METHODS: This paper presents a
      case report on an infant with diabetic ketoacidosis and in an extreme
      hyperosmolar and hypernatremic state. Considerations regarding appropriate fluid
      management and the osmotic role of serum sodium are discussed. Recommendations
      for treatment are given based on available guidelines and published evidence.
      INTERPRETATION: Intracellular swelling of the brain seems to be caused by water
      moving along osmotic gradients. In diabetic ketoacidosis, sodium and glucose are
      the dominant osmotic forces. It is important to understand the relation between
      serum osmolarity, sodium and glucose, as appropriate fluid treatment might
      prevent this potentially fatal complication.

PMID- 16276375
TI  - [Temporal arteritis and cerebrovascular complications].
AB  - BACKGROUND: Giant cell (temporal) arteritis is a systemic vasculitis of large and
      medium sized arteries causing severe visual loss and cerebrovascular accidents.
      We have treated several patients who developed stroke because of giant-cell
      arteritis despite high-dose corticosteroid treatment. METHODS: We undertook a
      Medline search in order to find predictive factors for risk of developing
      irreversible ischaemic complications in giant-cell arteritis. There are only a
      few reported cases in the literature, mostly retrospective studies. RESULTS:
      Stroke is a relatively rare neurologic complication, preceded by transient visual
      disturbances and jaw claudication. On the other hand, it is suggested that the
      rate of cranial ischaemic complications is inversely related to the intensity of
      inflammatory response. CONCLUSIONS: Cranial ischaemic complications can occur
      despite corticosteroid treatment. Low-dose aspirin as adjuvant therapy should be
      considered in patients with giant cell arteritis. Large, multicentre, randomized
      studies are required in order to define the best treatment for giant cell
      arteritis and for the prevention of cerebrovascular complications.

PMID- 16276377
TI  - [Postoperative cardiovascular complications].
AB  - BACKGROUND: It has been estimated that up to 25% of non-cardiac surgical
      procedures carry a significant risk of perioperative cardiovascular morbidity and
      mortality. A thorough preoperative evaluation with subsequent relevant diagnostic
      or therapeutic action can reduce the risk of postoperative complications in high
      risk patients. The purpose of the present study was to compare clinical practice
      in a medium-sized Norwegian hospital with international recommendations regarding
      perioperative evaluation and care. PATIENTS AND METHODS: We performed a
      registration of all patients transferred to the coronary care unit after surgery-
      retrospectively for 2002, prospectively for 2003. RESULTS: A total of 55 patients
      with one or more postoperative complication were identified, out of which 28 had
      been through elective surgery. Forty-four of the patients suffered an acute
      myocardial infarction. At 30 days, 15 of the patients had died and a further 13
      had sequelae. At 90 days, 22 patients were dead. The patients with complications
      were characterised by advanced age and high risk of cardiovascular disease. Out
      of the 55 patients, 8 were incorrectly scored for preoperative risk with American
      Society of Anaesthesiology's system for classification. For another 3, the score
      was missing. At discharge from the coronary care unit, only 1 out of 55 patients
      received a diagnosis of a postoperative complication. INTERPRETATION: The
      registration indicates that there is a potential for improving clinical practice
      in order to reduce the number of postoperative complications.

PMID- 16276376
TI  - [Chronic whiplash syndrome is no indication for craniocervical fixation].
AB  - Throughout many years, a large number of publications have focused on structural
      changes in soft tissues in the cervical spine in patients with whiplash
      associated disorders I-II. In recent years the development in MRI techniques have
      made it possible to visualize the small ligaments in the craniocervical junction;
      a small number of publications have investigated the association between signal
      changes in these ligaments and whiplash associated disorders I-II. The results
      are, however, not conclusive, and no prospective studies have demonstrated any
      causal connection between type of whiplash injury and signal changes in these
      ligaments. Craniocervical fixation is major surgery with a moderate level of
      perioperative complications. There is also a theoretical risk of increasing the
      degenerative process in the level below the fixation. The indications for
      craniocervical fixation are now serious conditions like instability caused by
      rheumatic arthritis, tumours and fractures. The scientific evidence for
      introducing a new indication for craniocervical fixation is lacking, and
      craniocervical fixation in WAD I-II must be considered experimental surgery.

PMID- 16276378
TI  - [Carotid endarterectomy in patients with coronary heart disease].
AB  - BACKGROUND: Patients with coexistent coronary and carotid artery disease are at
      high risk of developing stroke following coronary artery bypass grafting (CABG)
      and at the same time at increased risk of myocardial infarction when subjected to
      carotid endarterectomy (CEA). In patients with pronounced symptoms from both
      vascular territories, some institutions advocate a combined approach, with both
      CABG and CEA performed during the same period of anaesthesia. MATERIAL AND
      METHODS: We reviewed the medical records of patients who underwent the combined
      procedure between 1986 and 2004 (n = 37; group 1) and compared them to patients
      with coronary artery disease who underwent isolated CEA over the same period of
      time (n = 118; group 2). RESULTS: The ASA score, NYHA class, prevalence of
      peripheral artery disease, atrial fibrillation and contralateral carotid
      occlusion were significantly higher in group 1. Two patients (5.4%) in group 1
      and five patients (4.2%) in group 2 suffered a stroke. Five of these were
      ipsilateral to the CEA. Six patients had a perioperative myocardial infarction,
      one in group 1 (2.7%) and five (4.2%) in group 2 (ns). There were no deaths in
      group 1 and three deaths (2.5%) in group 2 during the first 30 days after
      surgery. The cumulative risk of death, stroke and myocardial infarction within 30
      days was 8.1% in group 1 and 11.0% in group 2. INTERPRETATION: Patients with
      coexistent atherosclerosis of the coronary and carotid arteries who underwent the
      combined procedure seem to have the same perioperative risk as patients with
      coronary artery disease who underwent isolated CEA, in spite of the fact that the
      former had a more generalised atherosclerotic disease.

PMID- 16276379
TI  - [Treatment of asthma--an analysis of clinical judgment among general
      practitioners].
AB  - BACKGROUND: The asthma patient's symptoms, use of drugs, and peak expiratory flow
      rates dictate treatment of asthma according to the guidelines. Our aim was to
      examine which information influenced the decisions of general practitioners.
      MATERIAL AND METHODS: Out of 100 general practitioners attending a course on
      asthma management, 75 responded to several constructed patient cases on asthma
      treatment. They decided whether or not to give oral steroids in case of an acute
      exacerbation and judged the quality of pharmacological treatment. Age, symptoms,
      body temperature, peak expiratory flow measurement and the dose of beta-2
      agonists and inhaled steroids varied from patient to patient. Their attitudes to
      the use of oral steroids and to the usefulness of measuring peak expiratory flow
      were evaluated. RESULTS: Among the doctors, 52% evaluated only one characteristic
      of the patients when deciding upon treatment with oral steroids. The use of drugs
      was evaluated by one quarter of the doctors when they judged the quality of
      treatment. Respectively, 81% and 73% were influenced by objective measurements in
      these decisions. The majority of doctors applied oral steroids and measured peak
      expiratory flow in asthmatics. INTERPRETATION: This study indicates that general
      practitioners focus mainly on measured peak expiratory flow rate. The patient's
      symptoms ought to be given more consideration in the treatment of asthma. The
      patient's use of anti-asthmatics is emphasised in guidelines, but was of only
      limited importance to the doctors in this study.

PMID- 16276380
TI  - [CYP genotyping in psychopharmacological treatment].

PMID- 16276381
TI  - [Molecular diagnostics in endocrine diseases].
AB  - Molecular diagnostic techniques provide an unsurpassed opportunity to understand
      the pathophysiological basis of endocrine disorders. Diseases have been
      associated with mutations in almost every gene known to have a role in either the
      production or secretion of a hormone or the mediators of hormone signalling. Even
      though most of these mutations are rare and account for only a small fraction of
      endocrine diseases, molecular diagnostics offers a valuable tool for the
      clinician in these cases. The most common endocrine disorders such as autoimmune
      thyroiditis, type 2 diabetes mellitus, osteoporosis, growth disorders, and
      obesity have all major genetic components, but these are mostly unknown. In this
      review the clinical implications of molecular diagnostics are illustrated for
      some endocrine diseases: congenital adrenal hyperplasia, congenital
      hypothyroidism, thyroid hormone resistance, familial hypocalciuric
      hypercalcaemia, growth hormone deficiency and resistance, and monogenic obesity.
      Improved diagnostic specificity has direct implications for treatment and follow
      up in these syndromes. Molecular diagnostics in endocrine tumours and diabetes
      are presented in two other articles in this series.

PMID- 16276382
TI  - [Hereditary endocrine tumour diseases].
AB  - BACKGROUND AND METHOD: The paper reviews inheritable endocrine tumour syndromes
      based on recent literature and the experience of the authors. RESULTS AND
      CONCLUSIONS: A number of inheritable endocrine tumour syndromes are caused by
      mutations in proto-oncogenes or tumour suppressor genes. These include multiple
      endocrine neoplasia (MEN), familial non-MEN neoplasia, Von Hippel-Lindau's
      disease and familial medullary thyroid carcinoma, pheochromocytoma and
      paraganglioma. These conditions are rare, but since inheritance is dominant with
      a near-complete penetrance, a number of carriers with a high risk of developing
      tumours are regularly found in the families of affected individuals.
      Identification of carriers with a high risk of developing tumours gives the
      opportunity to cure disease manifestations at an early stage and to avoid life
      threatening complications. Family members who are not carriers can be excluded
      from follow up. DNA analyses of the most common disease genes are now performed
      in genetic laboratories in Norway.

PMID- 16276383
TI  - [Molecular diagnostics in diabetes mellitus].
AB  - BACKGROUND: Genetic factors are involved in the development of diabetes. We here
      evaluate the possibilities for a genetic diagnosis of diabetes. METHODS: This
      overview is based on a limited literature search in PubMed as well as our own
      experience. RESULTS AND INTERPRETATION: Sequence variations in a number of genes
      and genomic regions result in an increased risk for development of type 1 and
      type 2 diabetes. With the exception of the HLA genes and their association with
      type 1 diabetes, these sequence variations each cause only a modest increase in
      diabetes risk. In contrast, disease-causing mutations can be identified in six
      genes associated with maturity-onset diabetes of the young (MODY). In most
      countries, MODY2 and MODY3 are the most frequent subtypes. Sulphonylurea may be
      the drug of choice when treating MODY3 because sensitivity for the drug is
      preserved even after long duration of diabetes. Neonatal diabetes is often caused
      by mutations in a component (Kir6.2) of the potassium channel of the beta cell.
      Patients can be managed on oral sulphonylurea with sustained metabolic control
      rather than on insulin injections.

PMID- 16276384
TI  - [Diagnosis versus code].
AB  - BACKGROUND: As a result of information about coding practice in a regional
      hospital, the Norwegian Board of Health carried out a special supervision of ear,
      nose and throat (ENT) departments and neurological departments during the autumn
      of 2003 and the spring of 2004. The aim was to investigate whether there was
      accordance between information in the patient records and the chosen diagnoses
      and codes. MATERIAL AND METHOD: Three hospitals were examined. Information in 100
      selected patient records from each department was compared with diagnoses and
      codes. The codes reported to the Norwegian Patient Register (NPR) from two
      hospitals were compared with codes in the patient records. RESULTS: Incorrect
      diagnoses had been systematically recorded in one ENT department. Incorrect codes
      had been recorded in all the departments, especially the neurological
      departments. Many inconsistencies between codes in the patient records and those
      reported to NPR were found. INTERPRETATION: Wrong diagnoses were seldom made, but
      many diagnoses were unprecise because only ICD-10 diagnoses were used. The rules
      of coding hospital stays were frequently not used. Many of the codes reported to
      NPR had been altered, without medical basis and without being noted in the
      patients' records.

PMID- 16276385
TI  - [National health resources for highly specialised medicine].
AB  - BACKGROUND: In order to monitor quality and efficiency in the use of health
      resources for highly specialised medicine, a National Professional Council has
      since 1990 advised the Norwegian health authorities on the establishing and
      localisation of such services. MATERIALS AND METHOD: A comprehensive review of
      both the quality, economy and the geographical distribution of patients in each
      specialised service has been carried out. RESULTS: 33 defined national programmes
      were centralised to one hospital only and distributed among seven university
      hospitals. Eight multiregional programmes were centralised to two hospitals only
      and included four university hospitals. In 2001, a total of 2711 new patients
      were treated in these programmes. The system seems to have secured a sufficient
      patient flow to each programme so as to maintain quality. However, a
      geographically skewed distribution of patients was noted, particularly in some of
      the national programmes. INTERPRETATION: In a small country like Norway, with 4.5
      million inhabitants, a centralised monitoring of highly specialised medicine
      seems both rational and successful. By the same logic, however, international
      cooperation should probably be sought for the smallest patient groups.

PMID- 16276387
TI  - [Reduction of sick leave a task for physicians?].

PMID- 16276386
TI  - [Medical monopolies--a choice between quality and equality?].
AB  - BACKGROUND: The highly specialised medical services in Norway consist of 33
      monopolies and 8 bipolies, involving both a duty of referral and a duty of
      admittance for defined patient groups. All the specialised services are located
      to large hospitals in southern Norway. MATERIAL: In conjunction with a thorough
      review of the specialised services, the geographical distribution of the 2711
      patients treated in 2001 was analysed. RESULTS: The geographical distribution was
      highly skewed, with a decreasing coverage with increasing distances from the
      monopoly centres. The ratio between the county with the most and the one with the
      least use of the services was 2.3. Northern Norway had a significantly lower
      usage. INTERPRETATION: Monopolies seem to have an inherent tendency to give poor
      distribution of health care. Medical monopolies seem to have many of the negative
      effects associated with economic monopolies. A cautious attitude towards new and
      a rigid control of old monopolies is recommended. Equality of access to services
      should be maintained as a primary goal in public health care systems.

PMID- 16276389
TI  - [Upheavals for better health services].

PMID- 16276390
TI  - [What does "patient in centre" mean?].

PMID- 16276391
TI  - [New blood tests for determination of tuberculosis].

PMID- 16276392
TI  - [Circus or tragedy?].

PMID- 16276393
TI  - [Overactive bladder syndrome].

PMID- 16276394
TI  - [Micturating urethrocystography of children].

PMID- 16276396
TI  - [Winter depression].

PMID- 16276398
TI  - [Are epicrises important medical documents?].

PMID- 16276400
TI  - [Anticoagulation therapy and oral surgery].

PMID- 16276404
TI  - Expression of procyclin mRNAs during cyclical transmission of Trypanosoma brucei.
AB  - Trypanosoma brucei, the parasite causing human sleeping sickness, relies on the
      tsetse fly for its transmission. In the insect, EP and GPEET procyclins are the
      major surface glycoproteins of procyclic (midgut) forms of the parasite, with
      GPEET predominating in the early procyclic form and two isoforms of EP in the
      late procyclic form. EP procyclins were previously detected on salivary gland
      trypanosomes, presumably epimastigotes, by immunoelectron microscopy. However, no
      procyclins could be detected by mass spectrometry when parasites were isolated
      from infected glands. We have used qualitative and quantitative RT-PCR to analyse
      the procyclin mRNAs expressed by trypanosomes in the tsetse midgut and salivary
      glands at different time points after infection. The coding regions of the three
      EP isoforms (EP1, EP2 and EP3) are extremely similar, but their 3' untranslated
      regions contain unique sequences that make it possible to assign the cDNAs
      amplified by this technique. With the exception of EP2, we found that the
      spectrum of procyclin mRNAs expressed in the midgut mirrors the protein
      repertoire of early and established procyclic forms. Surprisingly, procyclin
      mRNAs, including that of GPEET, are present at relatively high levels in salivary
      gland trypanosomes, although the proteins are rarely detected by
      immunofluorescence. Additional experiments using transgenic trypanosomes
      expressing reporter genes or mutant forms of procyclin point to a mechanism of
      translational or post-translational control, involving the procyclin coding
      regions, in salivary gland trypanosomes. It is widely accepted that T. brucei
      always has a coat of either variant surface glycoprotein or procyclin. It has
      been known for many years that the epimastigote form does not have a variant
      surface glycoprotein coat. The finding that this life cycle stage is usually
      negative for procyclin as well is new, and means that the paradigm will need to
      be revised.

PMID- 16276405
TI  - Displaced docs and researchers ride out the storm.

PMID- 16276403
TI  - Elucidation of clathrin-mediated endocytosis in tetrahymena reveals an
      evolutionarily convergent recruitment of dynamin.
AB  - Ciliates, although single-celled organisms, contain numerous subcellular
      structures and pathways usually associated with metazoans. How this cell
      biological complexity relates to the evolution of molecular elements is unclear,
      because features in these cells have been defined mainly at the morphological
      level. Among these ciliate features are structures resembling clathrin-coated,
      endocytic pits associated with plasma membrane invaginations called parasomal
      sacs. The combination of genome-wide sequencing in Tetrahymena thermophila with
      tools for gene expression and replacement has allowed us to examine this pathway
      in detail. Here we demonstrate that parasomal sacs are sites of clathrin
      dependent endocytosis and that AP-2 localizes to these sites. Unexpectedly,
      endocytosis in Tetrahymena also involves a protein in the dynamin family, Drp1p
      (Dynamin-related protein 1). While phylogenetic analysis of AP subunits indicates
      a primitive origin for clathrin-mediated endocytosis, similar analysis of dynamin
      related proteins suggests, strikingly, that the recruitment of dynamin-family
      proteins to the endocytic pathway occurred independently during the course of the
      ciliate and metazoan radiations. Consistent with this, our functional analysis
      suggests that the precise roles of dynamins in endocytosis, as well as the
      mechanisms of targeting, differ in metazoans and ciliates.

PMID- 16276406
TI  - UCLA director gets the goods as California makes good on its stem cell
      initiative. Interview by Stacie Bloom.

PMID- 16276407
TI  - B cells: no longer bystanders in liver fibrosis.
AB  - Cytokines secreted by cells that mediate the innate and adaptive immune responses
      play a critical role in regulating the synthesis of ECM components by
      fibroblasts. Overexpression and deposition of ECM components are dominant
      features of fibrotic diseases, including hepatic fibrosis. The contribution of
      CD4+ Th2 cells to hepatic fibrosis has been well described. Now, in this issue of
      the JCI, Novobrantseva et al. provide data to suggest that hepatic B cells also
      play a role in liver injury (see the related article beginning on page 3072). In
      a carbon tetrachloride-induced mouse model of hepatic fibrosis, T cell-deficient
      mice developed severe liver fibrosis; however, in B cell-deficient animals,
      hepatic fibrosis was attenuated. This study provides new insight into our
      understanding of the cells involved in mediating the adaptive immune response
      that leads to hepatic fibrosis.

PMID- 16276408
TI  - CD36 may determine our desire for dietary fats.
AB  - There is a strong link between high fat intake and obesity. In addition to its
      high caloric density, dietary fat has a hyperphagic effect, in part as a result
      of its high palatability. The recent identification by Laugerette et al. of CD36
      as a taste receptor for fatty acids provides insight into the molecular basis of
      our preference for fat (see the related article beginning on page 3177). As we
      gain more information regarding the function of this receptor, we may be able to
      devise better strategies to address the addictive potential of dietary fat.

PMID- 16276409
TI  - All neuropathies great and small.
AB  - Autosomal-dominant pure hereditary spastic paraplegia (AD-HSP) is characterized
      by the degeneration of long axons in corticospinal tracts and dorsal columns,
      resulting in spasticity and difficulty walking. Mutations in the SPG4 gene
      product spastin are the predominant genetic lesions associated with this
      inherited disease. In this issue, Orso et al. examine and reconcile existing
      Drosophila mutants of spastin and generate a new model for HSP by overexpression
      of a fly spastin transgene that carries a mutation prevalent in human AD-HSP (see
      the related article beginning on page 3026). Expression of this mutant spastin
      protein produces pathology in flies reminiscent of the human disease, including
      adult locomotion defects, in addition to causing aberrant synaptic morphology and
      altered microtubule stability. Both movement and synaptic defects in fly mutants
      were ameliorated by treatment with the microtubule-modifying agent vinblastine.
      The results are consistent with disease-causing mutations in human spastin
      producing dominant-negative proteins and confirm the usefulness of Drosophila
      genetic techniques to understand HSP and other neurodegenerative diseases.

PMID- 16276410
TI  - When 7 transmembrane receptors are not G protein-coupled receptors.
AB  - Classically, 7 transmembrane receptors transduce extracellular signals by
      coupling to heterotrimeric G proteins, although recent in vitro studies have
      clearly demonstrated that they can also signal via G protein-independent
      mechanisms. However, the physiologic consequences of this unconventional
      signaling, particularly in vivo, have not been explored. In this issue of the
      JCI, Zhai et al. demonstrate in vivo effects of G protein-independent signaling
      by the angiotensin II type 1 receptor (AT1R) (see the related article beginning
      on page 3045). In studies of the mouse heart, they compare the physiologic and
      biochemical consequences of transgenic cardiac-specific overexpression of a
      mutant AT1R incapable of G protein coupling with those of a wild-type receptor.
      Their results not only provide the first glimpse of the physiologic effects of
      this newly appreciated mode of signaling but also provide important and
      previously unappreciated clues as to the underlying molecular mechanisms.

PMID- 16276411
TI  - Variable phenotypic expression of mutations in genes of the immune system.
AB  - Discovery of mutated genes that cause various types of primary immunodeficiencies
      has significantly advanced our understanding of the pathogenesis of these
      diseases and of the functions of normal gene products. However, it is becoming
      abundantly clear that the phenotypic presentation of mutations in a given gene
      can be quite different, depending upon the location and type of mutation but also
      probably upon other genetic factors and environmental influences. In this issue
      of the JCI, de Villartay et al. describe a third phenotype for mutations in
      recombination activating gene 1 (RAG1), in addition to the already known
      phenotypes of SCID and Omenn syndrome (see the related article beginning on page
      3291).

PMID- 16276412
TI  - New insights into nNOS regulation of vascular homeostasis.
AB  - An important physiological response to changes in local or systemic oxygenation
      is the modulation of vascular tone, which is mediated in part by changes in the
      activities of the 3 NO synthase (NOS) isoforms. In arterial smooth muscle cells,
      acute hypoxia induces increased vascular tone, which is attenuated if hypoxia
      persists. In this issue of the JCI, Ward et al. demonstrate that changes in O2
      concentration have effects on neuronal NOS enzymatic activity and gene expression
      that contribute to vascular homeostasis under conditions of acute and chronic
      hypoxia (see the related article beginning on page 3128).

PMID- 16276413
TI  - Disease-related phenotypes in a Drosophila model of hereditary spastic paraplegia
      are ameliorated by treatment with vinblastine.
AB  - Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative diseases
      characterized by progressive weakness and spasticity of the lower limbs. Dominant
      mutations in the human SPG4 gene, encoding spastin, are responsible for the most
      frequent form of HSP. Spastin is an ATPase that binds microtubules and localizes
      to the spindle pole and distal axon in mammalian cell lines. Furthermore, its
      Drosophila homolog, Drosophila spastin (Dspastin), has been recently shown to
      regulate microtubule stability and synaptic function at the Drosophila larval
      neuromuscular junction. Here we report the generation of a spastin-linked HSP
      animal model and show that in Drosophila, neural knockdown of Dspastin and,
      conversely, neural overexpression of Dspastin containing a conserved pathogenic
      mutation both recapitulate some phenotypic aspects of the human disease,
      including adult onset, locomotor impairment, and neurodegeneration. At the
      subcellular level, neuronal expression of both Dspastin RNA interference and
      mutant Dspastin cause an excessive stabilization of microtubules in the
      neuromuscular junction synapse. In addition, we provide evidence that
      administration of the microtubule targeting drug vinblastine significantly
      attenuates these phenotypes in vivo. Our findings demonstrate that loss of
      spastin function elicits HSP-like phenotypes in Drosophila, provide novel
      insights into the molecular mechanism of spastin mutations, and raise the
      possibility that therapy with Vinca alkaloids may be efficacious in spastin
      associated HSP and other disorders related to microtubule dysfunction.

PMID- 16276414
TI  - GM-CSF action in the CNS decreases food intake and body weight.
AB  - Many proinflammatory cytokines, such as leptin, play key roles in dynamic
      regulation of energy expenditure and food intake. The present work tested a role
      for the proinflammatory cytokine GM-CSF. Central but not peripheral
      administration of GM-CSF to adult rats significantly decreased food intake and
      body weight for at least 48 hours. Similar results were observed following
      central administration of GM-CSF in mice. GM-CSF receptor immunoreactivity was
      found on neurons within the paraventricular and arcuate nuclei of the
      hypothalamus. GM-CSF-deficient (GM-/-) mice weighed more and had significantly
      higher total body fat than wild-type (GM+/+) mice. Energy expenditure in GM-/-
      mice was decreased compared with that in GM+/+ mice. Taken together, these
      findings demonstrate that GM-CSF signaling in the CNS can regulate energy
      homeostasis.

PMID- 16276415
TI  - Cardiac-specific overexpression of AT1 receptor mutant lacking G alpha q/G alpha
      i coupling causes hypertrophy and bradycardia in transgenic mice.
AB  - Ang II type 1 (AT1) receptors activate both conventional heterotrimeric G protein
      dependent and unconventional G protein-independent mechanisms. We investigated
      how these different mechanisms activated by AT1 receptors affect growth and death
      of cardiac myocytes in vivo. Transgenic mice with cardiac-specific overexpression
      of WT AT1 receptor (AT1-WT; Tg-WT mice) or an AT1 receptor second intracellular
      loop mutant (AT1-i2m; Tg-i2m mice) selectively activating G(alpha)q/G(alpha)i
      independent mechanisms were studied. Tg-i2m mice developed more severe cardiac
      hypertrophy and bradycardia coupled with lower cardiac function than Tg-WT mice.
      In contrast, Tg-WT mice exhibited more severe fibrosis and apoptosis than Tg-i2m
      mice. Chronic Ang II infusion induced greater cardiac hypertrophy in Tg-i2m
      compared with Tg-WT mice whereas acute Ang II administration caused an increase
      in heart rate in Tg-WT but not in Tg-i2m mice. Membrane translocation of
      PKCepsilon, cytoplasmic translocation of G(alpha)q, and nuclear localization of
      phospho-ERKs were observed only in Tg-WT mice while activation of Src and
      cytoplasmic accumulation of phospho-ERKs were greater in Tg-i2m mice, consistent
      with the notion that G(alpha)q/G(alpha)i-independent mechanisms are activated in
      Tg-i2m mice. Cultured myocytes expressing AT1-i2m exhibited a left and upward
      shift of the Ang II dose-response curve of hypertrophy compared with those
      expressing AT1-WT. Thus, the AT1 receptor mediates downstream signaling
      mechanisms through G(alpha)q/G(alpha)i-dependent and -independent mechanisms,
      which induce hypertrophy with a distinct phenotype.

PMID- 16276416
TI  - Attenuated liver fibrosis in the absence of B cells.
AB  - Analysis of mononuclear cells in the adult mouse liver revealed that B cells
      represent as much as half of the intrahepatic lymphocyte population. Intrahepatic
      B cells (IHB cells) are phenotypically similar to splenic B2 cells but express
      lower levels of CD23 and CD21 and higher levels of CD5. IHB cells proliferate as
      well as splenic B cells in response to anti-IgM and LPS stimulation in vitro. VDJ
      gene rearrangements in IHB cells contain insertions of N,P region nucleotides
      characteristic of B cells maturing in the adult bone marrow rather than in the
      fetal liver. To evaluate whether B cells can have an impact on liver pathology,
      we compared CCl4-induced fibrosis development in B cell-deficient and wild-type
      mice. CCl4 caused similar acute liver injury in mutant and wild-type mice.
      However, following 6 weeks of CCl4 treatment, histochemical analyses showed
      markedly reduced collagen deposition in B cell-deficient as compared with wild
      type mice. By analyzing mice that have normal numbers of B cells but lack either
      T cells or immunoglobulin in the serum, we established that B cells have an
      impact on fibrosis in an antibody- and T cell-independent manner.

PMID- 16276417
TI  - Staphylococcus aureus Panton-Valentine leukocidin directly targets mitochondria
      and induces Bax-independent apoptosis of human neutrophils.
AB  - Panton-Valentine leukocidin (PVL) is a pore-forming toxin secreted by
      Staphylococcus aureus that has recently been associated with necrotizing
      pneumonia. In the present study, we report that in vitro, PVL induces
      polymorphonuclear cell death by necrosis or by apoptosis, depending on the PVL
      concentration. PVL-induced apoptosis was associated with a rapid disruption of
      mitochondrial homeostasis and activation of caspase-9 and caspase-3, suggesting
      that PVL-induced apoptosis is preferentially mediated by the mitochondrial
      pathway. Polymorphonuclear cell exposure to PVL leads to mitochondrial
      localization of the toxin, whereas Bax, 1 of the 2 essential proapoptotic members
      of the Bcl-2 family, was still localized in the cytosol. Addition of PVL to
      isolated mitochondria induced the release of the apoptogenic proteins cytochrome
      c and Smac/DIABLO. Therefore, we suggest that PVL, which belongs to the pore
      forming toxin family, could act at the mitochondrion level by creating pores in
      the mitochondrial outer membrane. Furthermore, LukS-PV, 1 of the 2 components of
      PVL, was detected in lung sections of patients with necrotizing pneumonia
      together with DNA fragmentation, suggesting that PVL induces apoptosis in vivo
      and thereby is directly involved in the pathophysiology of necrotizing pneumonia.

PMID- 16276418
TI  - Hypoxia induces a functionally significant and translationally efficient neuronal
      NO synthase mRNA variant.
AB  - We tested the hypothesis that induction of neuronal NO synthase (nNOS) impairs
      vascular smooth muscle contractility after hypoxia. nNOS protein was increased in
      aorta, mesenteric arterioles, pulmonary arteries, brain, and diaphragm from rats
      exposed to 8% O2 for 48 hours and in human aortic SMCs after hypoxic incubation
      (1% O2). Ca-dependent NO synthase activity was increased in endothelium-denuded
      aortic segments from hypoxia-exposed rats. N-nitro-L-arginine methyl ester
      enhanced the contractile responses of endothelium-denuded aortic rings and
      mesenteric arterioles from hypoxia-exposed but not normoxic rats (P < 0.05). The
      hypoxia-inducible mRNA transcript expressed by human cells was found to contain a
      novel 5'-untranslated region, consistent with activation of transcription in the
      genomic region contiguous with exon 2. Translational efficiency of this
      transcript is markedly increased compared with previously described human nNOS
      mRNAs. Transgenic mice possessing a lacZ reporter construct under control of
      these genomic sequences demonstrated expression of the construct after exposure
      to hypoxia (8% O2, 48 hours) in the aorta, mesenteric arterioles, renal papilla,
      and brain. These results reveal a novel human nNOS promoter that confers the
      ability to rapidly upregulate nNOS expression in response to hypoxia with a
      functionally significant effect on vascular smooth muscle contraction.

PMID- 16276419
TI  - CD36 involvement in orosensory detection of dietary lipids, spontaneous fat
      preference, and digestive secretions.
AB  - Rats and mice exhibit a spontaneous attraction for lipids. Such a behavior raises
      the possibility that an orosensory system is responsible for the detection of
      dietary lipids. The fatty acid transporter CD36 appears to be a plausible
      candidate for this function since it has a high affinity for long-chain fatty
      acids (LCFAs) and is found in lingual papillae in the rat. To explore this
      hypothesis further, experiments were conducted in rats and in wild-type and CD36
      null mice. In mice, RT-PCR experiments with primers specific for candidate lipid
      binding proteins revealed that only CD36 expression was restricted to lingual
      papillae although absent from the palatal papillae. Immunostaining studies showed
      a distribution of CD36 along the apical side of circumvallate taste bud cells.
      CD36 gene inactivation fully abolished the preference for LCFA-enriched solutions
      and solid diet observed in wild-type mice. Furthermore, in rats and wild-type
      mice with an esophageal ligation, deposition of unsaturated LCFAs onto the tongue
      led to a rapid and sustained rise in flux and protein content of pancreatobiliary
      secretions. These findings demonstrate that CD36 is involved in oral LCFA
      detection and raise the possibility that an alteration in the lingual fat
      perception may be linked to feeding dysregulation.

PMID- 16276420
TI  - Synaptic activity becomes excitotoxic in neurons exposed to elevated levels of
      platelet-activating factor.
AB  - Neurologic impairment in HIV-1-associated dementia (HAD) and other
      neuroinflammatory diseases correlates with injury to dendrites and synapses, but
      how such injury occurs is not known. We hypothesized that neuroinflammation makes
      dendrites susceptible to excitotoxic injury following synaptic activity. We
      report that platelet-activating factor, an inflammatory phospholipid that
      mediates synaptic plasticity and neurotoxicity and is dramatically elevated in
      the brain during HAD, promotes dendrite injury following elevated synaptic
      activity and can replicate HIV-1-associated dendritic pathology. In hippocampal
      slices exposed to a stable platelet-activating factor analogue, tetanic
      stimulation that normally induces long-term synaptic potentiation instead
      promoted development of calcium- and caspase-dependent dendritic beading.
      Chemical preconditioning with diazoxide, a mitochondrial ATP-sensitive potassium
      channel agonist, prevented dendritic beading and restored long-term potentiation.
      In contrast to models invoking excessive glutamate release, these results suggest
      that physiologic synaptic activity may trigger excitotoxic dendritic injury
      during chronic neuroinflammation. Furthermore, preconditioning may represent a
      novel therapeutic strategy for preventing excitotoxic injury while preserving
      physiologic plasticity.

PMID- 16276421
TI  - HIV-infected individuals receiving effective antiviral therapy for extended
      periods of time continually replenish their viral reservoir.
AB  - The persistence of latently infected, resting CD4+ T cells is considered to be a
      major obstacle in preventing the eradication of HIV-1 even in patients who have
      received effective antiviral therapy for an average duration of 5 years. Although
      previous studies have suggested that the latent HIV reservoir in the resting CD4+
      T cell compartment is virologically quiescent in the absence of activating
      stimuli, evidence has been mounting to suggest that low levels of ongoing viral
      replication persist and in turn, prolong the overall half-life of HIV in patients
      receiving antiviral therapy. Here, we demonstrate the persistence of replication
      competent virus in CD4+ T cells in a cohort of patients who had received
      uninterrupted antiviral therapy for up to 9.1 years that rendered them
      consistently aviremic throughout that time. Surprisingly, substantially higher
      levels of HIV proviral DNA were found in activated CD4+ T cells when compared
      with resting CD4+ T cells in the majority of patients we studied. Phylogenetic
      analyses revealed evidence for cross infection between the resting and activated
      CD4+ T cell compartments, suggesting that ongoing reactivation of latently
      infected, resting CD4+ T cells and spread of virus by activated CD4+ T cells may
      occur in these patients. Such events may allow continual replenishment of the
      CD4+ T cell reservoir and resetting of the half-life of the latently infected,
      resting CD4+ T cells despite prolonged periods of aviremia.

PMID- 16276424
TI  - The World Federation of Orthodontists: work in progress.

PMID- 16276422
TI  - A novel immunodeficiency associated with hypomorphic RAG1 mutations and CMV
      infection.
AB  - Amorphic mutations in the recombination activating genes RAG1 and RAG2 have been
      reported to cause T- B- SCID, whereas hypomorphic mutations led to the expansion
      of a few autoimmune T cell clones responsible for the Omenn syndrome phenotype.
      We report here a novel clinical and immunological phenotype associated with
      recessive RAG1 hypomorphic mutations in 4 patients from 4 different families. The
      immunological phenotype consists of the oligoclonal expansion of TCR gammadelta T
      cells combined with TCR alphabeta T cell lymphopenia. The clinical phenotype
      consists of severe, disseminated CMV infection and autoimmune blood cell
      manifestations. Repertoire studies suggest that CMV infection, in the setting of
      this particular T cell immunodeficiency, may have driven the TCR gammadelta T
      cell clonal expansion. This observation extends the range of clinical and
      immunological phenotypes associated with RAG mutations, emphasizing the role of
      the genetic background and microbial environment in determining disease
      phenotype.

PMID- 16276425
TI  - European community legislation concerning schools of specialisation in
      orthodontics: the inexplicable inertia of Italy--contradictions and open issues.
AB  - Orthodontics was the first discipline to be acknowledged as such within the field
      of dentistry, initially in the USA and subsequently in Europe. The structural
      changes that led to the birth of the European Union (EU) laid the foundations for
      the free circulation of professions and services. Nevertheless a deep discrepancy
      in the quality of training of practitioners from different countries became
      apparent. It was necessary to address this issue and regulate the training
      process in order to guarantee a degree of uniformity. Up to this time only the
      duration of the School of Specialisation in Orthodontics has been set at a
      minimum of three years. While moving towards an increasing degree of integration
      of the various EU countries, it becomes paramount to be able to establish a
      School of Specialisation in Orthodontics with high academic standards based on
      the Erasmus Programme and above all to be able to award a specialisation degree
      which is acknowledged first of all in the country where it is issued and also on
      a wider European level. Freedom of circulation of intellectual activities
      requires the formal acknowledgement of a qualification, namely the Specialisation
      in Orthodontics. Also to that end, EFOSA (European Federation of Specialists in
      Orthodontics) was founded. Furthermore the European Community has, in the
      meantime, ruled that medical trainees should be remunerated for their work.
      Dentistry and its specialisations should not follow the model of Medicine given
      that the two are completely distinct, but many believe that the duration of the
      School of Specialisation in Orthodontics has to be set as the same as the medical
      specialisations.

PMID- 16276426
TI  - Effective maxillary orthopedic protraction for growing Class III patients: a
      clinical application simulates distraction osteogenesis.
AB  - The effective maxillary orthopedic protraction is an innovative technique for
      maxillary protraction in Class III growing patients. It includes three
      components: a new 2-hinged rapid maxillary expander for a greater amount of
      anterior displacement of maxilla, repetitive weekly protocol of Alternate Rapid
      Maxillary Expansion and Constriction (Alt-RAMEC) for disarticulating the maxilla,
      and intraoral maxillary protraction springs for non-compliant protraction. On
      average, the maxilla could be protracted for 5.8 mm in 3 months and the result
      remains stable at least 2 years later. The rationale for this technique is
      sutural expansion/ protraction osteogenesis. Sutural expansion/ protraction
      osteogenesis is a form of distraction osteogenesis. However, it still needs to be
      scrutinized experimentally for the sutural reactions corresponding to the
      effective maxillary orthopedic protraction.

PMID- 16276427
TI  - Severe Class II division 1 malocclusion treated by orthodontic miniplate with
      tube.
AB  - A miniplate with tube (C-tube) was placed in the interdental spaces between both
      left and right upper second premolars and first molars in a 15-year-8 month-old
      male patient with a Class II malocclusion who with severe anterior protrusion and
      lower anterior crowding. The treatment plan consisted of extracting both upper
      first premolars, en masse retraction of the upper six anterior teeth and lower
      anterior decrowding. C-tubes were used as substitutes for posterior dental
      anchorage during upper anterior retraction. The particular design of the C-tubes
      made it possible to retract fully with minimal gingival irritation. The correct
      overbite and overjet were obtained by intruding and retracting the maxillary
      incisors to their proper positions and this correction remained stable for at
      least 27 months after debonding. Also, facial balance was improved. The active
      treatment period was 14 months. The application of this new appliance,
      consideration of case selection, and sequence of treatment are presented.

PMID- 16276428
TI  - Atypical treatment of Class II malocclusion with space closure only in the lower
      arch.
AB  - Two patients with Class II malocclusions and missing or previously extracted
      teeth in the lower arch were treated without compensatory upper extractions to a
      Class I canine and a Class III molar result. Indications and contra-indications
      are discussed and the case reports are shown, including long-term retention
      records.

PMID- 16276429
TI  - Temporomandibular dysfunction and repositioning splint therapy.
AB  - AIM: The purpose of this paper is assess the effectiveness of repositioning
      splint therapy in the treatment of Temporomandibular dysfunction (TMD). MATERIALS
      AND METHODS: 464 patients with TMD, characterized by an internal derangement and
      other symptoms including, but not limited to, jaw locking, pain to palpation,
      headaches, and crepitus, were treated with an anterior repositioning splint to
      recapture the disc, followed by a superior repositioning splint to allow the
      muscles to "seat" the condlyles in the fossae. RESULTS: 90% of the patients
      experienced a remission of the symptoms and were treated to a generally pain
      free, functionally satisfactory state. CONCLUSION: The response to treatment
      noted in the 464 patients indicate that repositioning splint therapy is an
      effective treatment modality for temporomandibular disorders.

PMID- 16276430
TI  - Computer-aided interactive indirect bonding.
AB  - INTRODUCTION: The introduction of the virtual occlusal set-up, limited to the
      permanent dentition with dento-dental and dento-alveolar discrepancies, based on
      the straight wire technique with final arches .020" x .025" ss in straight wire
      brackets .022" x .028" is an evolution of the 3D digital model with clinical
      impact. AIM: To present a computer-aided solution to orthodontic indirect
      bonding, allowing accurate positioning of straight-wire brackets based on a
      virtual occlusal set-up resulting from the treatment plan. MATERIAL AND METHODS:
      Computer-aided indirect bonding was applied in two cases: a Class II patient in
      the permanent dentition, crowding, rotation of upper and lower bicuspids and a
      Class I patient in the permanent dentition with already extracted 1.4, 2.4, 3.4,
      4.4, severe crowding, rotation, arch form reduction. Speed brackets were utilized
      in both cases. RESULTS: In the first case the brackets' starting position on the
      patient corresponds to the final position on the virtual occlusal set-up. In the
      second case the resulting occlusion at the end of treatment corresponds to the
      final occlusion on the virtual occlusal set-up. DISCUSSION: The computerized
      tools employed in the process enabled precise bracket placement on the stone
      model. An algorithm from the virtual set-up is the determinant for the precision.
      CONCLUSION: Computer aided indirect bonding is a method of placing brackets
      precisely.

PMID- 16276431
TI  - Temporomandibular disorders (TMD).

PMID- 16276432
TI  - Geometric organization of the extracellular matrix in the control of integrin
      mediated adhesion and cell function in osteoblasts.
AB  - Cell-extracellular matrix (ECM) interactions play a central role in tissue
      architecture and turnover. Particularly, integrin-mediated cell adhesion
      participates in biochemical and physical signals. The aim of this study is to
      investigate the importance of ECM organization for alveolar bone osteoblasts
      adhesion and to determine the effects on cell functions such as collagen and
      fibronectin production. By applying new concepts from the nanotechnology to
      biological systems, we have developed materials decorated with nano-patterns of
      peptides of the ECM arranged at a distance of 58 or 73 nm. On these surfaces,
      human osteoblasts from alveolar bone were cultured for 1-96 hr and examined by
      video and fluorescence microscopy. Protein quantification by western blotting and
      gene expression by RT-PCR were also performed. Good cell adhesion and spreading
      was observed on the 58 nm pattern after 30 min, while weak adhesion and increased
      motility was evident in osteoblasts on the 73 nm pattern, leading to alteration
      of cell shape and reduction of cell area after 24 hr. Moreover, cells on the 73
      nm did not form focal adhesions and failed to organize the cytoskeleton. After 96
      hr in culture, osteoblasts on the 73 nm retained intracellular collagen and
      produced a disorganized fibronectin network. Osteoblast adhesion and intra-and
      extra-cellular molecules reorganization are regulated not only by the composition
      but also by the structure of the extracellular environment. Our novel in vitro
      system makes it possible to elucidate some of the mechanisms necessary for the
      maintenance of tissue architecture and mechanical strength, as well as for the
      design of artificial materials for future clinical applications.

PMID- 16276434
TI  - Italian Board of Orthodontics: Case no 3 Class I Malocclusion.

PMID- 16276433
TI  - Transcription Factor Decoy (TFD) as a novel approach for the control of
      osteoclastic resorption.

PMID- 16276435
TI  - Multidisciplinary treatment of agenesis in the anterior and posterior areas: a
      long term retrospective analysis.
AB  - Twenty-two implants inserted in the anterior area in 15 patients, and 24 implants
      inserted in the posterior area in 9 patients, for a total of 46 implants in
      orthodontic patients suffering from single or multiple agenesis, were analyzed
      retrospectively. The average time of follow-up, subsequent to the prosthetic
      insertion was 60.3 months. The average time from actual diagnosis of agenesis to
      the completion of therapy was 76.2 months. There were no implant failures,
      although 17.4% experienced prosthetic complications. Analysis of the sample
      identified 5 critical issues that are frequently underestimated at the time of
      determining the therapeutic strategy. 1. Timely comprehensive management of the
      patient; 2. management of the biological interface (surgery and hygiene
      maintenance); 3. prosthetic problems; 4. long term effects of bone remodeling; 5.
      alternative therapy.

PMID- 16276436
TI  - Viral infections and prolonged fever after liver transplantation in young
      children with inborn errors of metabolism.
AB  - BACKGROUND AND PURPOSE: Liver transplantation could be a useful treatment for
      selected inborn errors of metabolism. This study evaluated the outcome and viral
      infections after liver transplantation in young children and infants with these
      diseases. METHODS: The outcome of liver transplantation and clinical
      characteristics of the following 4 patients were assessed: 1 infant with
      ornithine transcarbamylase deficiency (OTCD) who received liver transplant aged 3
      years and 4 months; 1 infant with carbamyl phosphate synthetase I deficiency
      (CPSID) who received liver transplant at 14 months of age; and 2 infants with
      methylmalonic acidemia (MMA) who received liver transplant at 8 months and 11
      months of age, respectively. All donors, except the 8-month-old infant with MMA,
      showed serologic evidence of previous cytomegalovirus (CMV) infection before
      transplantation. All 4 of these donors showed serologic evidence of previous
      infection of Epstein-Barr virus (EBV). None of the recipients had previous CMV
      infection. Both the infant with OTCD and the 8-month-old infant with MMA had
      previous EBV infection, while the other 2 patients did not. Preoperative
      hemodialysis was performed in both infants with MMA. Postoperative follow-up
      included metabolic stability, disability degree, and viral infections. RESULTS:
      None of the patients developed severe metabolic decompensation after
      transplantation and all increased protein intake postoperatively. Symptomatic
      viral infections, however, were present in all patients postoperatively,
      including CMV infection in the infant with OTCD and the 11-month-old infant with
      MMA, reactivation of EBV infection in the infant with OTCD and the 8-month-old
      infant with MMA, and primary EBV infection in the infant with CPSID. CONCLUSIONS:
      Liver transplantation was an effective treatment for all 4 of these patients with
      inborn errors of metabolism. The risk of symptomatic viral infections for these
      patients was high. This was likely associated with conditions including
      immunosuppression, young age, endemic nature of CMV and EBV infections, and lack
      of CMV prophylaxis.

PMID- 16276437
TI  - Vasomotion enhanced by normovolemic hemodilution in rat diaphragmatic
      microcirculation.
AB  - BACKGROUND AND PURPOSE: Since vasomotion--the rhythmic contraction and dilatation
      of arterioles--is frequently observed during homeostatic challenge, it has been
      assumed that vasomotion may cause the vulnerable portions of tissue to become
      intermittently oxygenated rather than permanently anoxic. This study used laser
      Doppler flowmetry to investigate the effect of normovolemic hemodilution on the
      incidence, frequency and relative amplitude of vasomotion in rat diaphragm
      microcirculation. METHODS: Blood was substituted normovolemically with equal
      volumes of a 6% solution of dextran 70 (molecular weight 70,000). Infrared light
      (wavelength 780 nm) was delivered to and detected from diaphragm tissue area
      approximately 1 mm in diameter and 0.5 mm in depth. The light scattered by a
      moving red blood cell results in a Doppler frequency shift. Vasomotion was
      analyzed with Fourier transformation and autoregressive modeling. RESULTS:
      Following hemodilution, systemic hematocrit showed a stepwise decrease of 4
      hemodilution levels (80%, 60%, 51%, and 43% of baseline values). Vasomotion was
      found in 13/20 (65%) at baseline, and 20/20 (100%) at the 43% level (p < 0.05
      from baseline). The median fundamental frequencies during the control state and
      at the 4 corresponding incremental hemodilution levels were 3.29 cycles per
      minute (cpm), 3.30 cpm, 3.14 cpm, 3.26 cpm, and 3.42 cpm (p < 0.05 from
      baseline). The median relative amplitudes at baseline and 4 hemodilution stages
      were 31.7%, 38.5%, 40.0% (p < 0.05 from baseline), 40.7% (p < 0.05 from
      baseline), and 41.6% (p < 0.05 from baseline). CONCLUSIONS: This study found that
      an acute reduction of systemic hematocrit greatly increased the activity of
      vasomotion in the diaphragm microvascular bed of rats, suggesting vasomotion
      could be a protective mechanism against tissue hypoxia.

PMID- 16276438
TI  - Predictors of survival and hospital outcome of prehospital cardiac arrest in
      southern Taiwan.
AB  - BACKGROUND AND PURPOSE: Despite recent improvements in emergency care medicine,
      outcome for prehospital cardiac arrest patients remains poor in southern Taiwan
      due to lack of training and authorization of emergency medical technicians to
      perform advanced life support. The purpose of this study was to analyze the
      characteristics of these patients and to identify possible predictive factors for
      final hospital discharge. METHODS: We retrospectively reviewed the
      characteristics of 361 prehospital cardiac arrest patients (male:female, 226:135;
      median age, 69 years) undergoing cardiopulmonary resuscitation (CPR) on arrival
      at the emergency department (ED) between January 1, 2001 and December 31, 2003.
      Multivariate analysis was performed by fitting explanatory variables into
      logistic regression models with respect to the outcomes of admission and to
      hospital discharge. RESULTS: The overall survival rate was 21.1% (n = 76) to
      hospital admission and 7.2% (26) to hospital discharge. About half (54%) of the
      26 patients who survived had cardiac disease. Only 3 patients received CPR from a
      bystander, and 2 of them survived. None of the patients received electrical
      defibrillation before arriving at hospital because emergency personnel were not
      authorized to perform advanced cardiac life support (ACLS) in Southern Taiwan
      during the study period. Factors that predicted survival to hospital discharge
      included a short interval between the cardiac arrest and arrival at the ED,
      initial rhythm of ventricular tachycardia/ventricular fibrillation (VT/VF), lower
      atropine dose, higher level of hemoglobin, less multiple organ failure, and
      shorter duration of resuscitation in the ED. Nine of the 32 patients (28%) with
      VT/VF survived compared with 5 of 49 (10%) with pulseless electrical activity and
      only 12 of 231 (5%) with asystole. No patients who required resuscitation for
      longer than 20 minutes in the ED survived to hospital discharge. CONCLUSION: The
      results of this study illustrate that patients with VT/VF have good potential for
      successful resuscitation. Prompt resuscitation and easy access for ACLS are the
      key factors for success. Survival rates are likely to improve if more lay people
      perform CPR and if emergency unit personnel are trained and allowed to perform
      ACLS.

PMID- 16276439
TI  - Differential analgesic effect of tenoxicam on post-cesarean uterine cramping pain
      between primiparous and multiparous women.
AB  - BACKGROUND AND PURPOSE: Uterine cramping pain is related to prostaglandins, which
      are mediated by cyclooxygenase. However, it is unknown whether the analgesic
      effects of the non-selective cyclooxygenase inhibitor tenoxicam are different
      between primiparous and multiparous women. This placebo-controlled, double-blind
      study compared the analgesic effect of tenoxicam on post-cesarean uterine
      cramping pain in primiparous and multiparous women. METHODS: Forty primiparous
      women and 40 multiparous women who were scheduled for elective cesarean delivery
      were allocated into the following 4 groups: saline-primipara (SP) group,
      tenoxicam-primipara (TP) group, saline-multipara (SM) group, and tenoxicam
      multipara (TM) group. Saline or 20 mg tenoxicam was intravenously injected
      immediately after clamping of the umbilical cord. All patients received patient
      controlled analgesia for postoperative pain control. Resting wound pain, uterine
      cramping pain, morphine consumption, and morphine-related side effects were
      evaluated at 4 and 24 hours after surgery. RESULTS: At 24 hours after surgery,
      tenoxicam-related relief of uterine cramping pain was 2.1 in primiparous women
      (visual analog scale: SP 5.6 (4.4-6.8) minus TP 3.5 (2.2-4.9); p < 0.01). The
      tenoxicam-related morphine-sparing effect was 14 mg (45%) in primiparous women
      (SP 31.4 mg (23.9-38.8) minus TP 17.4 mg (11.6-23.2); p < 0.01). The tenoxicam
      related relief of uterine cramping pain and tenoxicam-related morphine-sparing
      effect were not significant in multiparous women. CONCLUSIONS: This study
      revealed that the analgesic effect of tenoxicam on post-cesarean uterine cramping
      pain is greater in primiparous women than in multiparous women. Further studies
      are required to determine whether a higher dosage of tenoxicam is beneficial to
      reduce uterine cramping pain in multiparous women.

PMID- 16276440
TI  - In vitro gene expression changes of androgen receptor coactivators after hormone
      deprivation in an androgen-dependent prostate cancer cell line.
AB  - BACKGROUND AND PURPOSE: Androgen receptor (AR) coactivators modulate the
      transcriptional activity of AR and may activate AR-associated genes upon androgen
      deprivation. Changes of expression patterns may help reveal the role of AR
      cofactors in androgen-independent prostate cancer. This study investigated
      changes of expression patterns of several AR coactivators after androgen
      deprivation in an androgen-dependent prostate cancer cell line (LNCaP). METHODS:
      LNCaP cells were cultured in RPMI medium with charcoal/dextran-treated fetal
      bovine serum for 28 days. Samples of total RNA collected at 1-week intervals were
      analyzed using a non-isotopic multi-probe ribonuclease protection assay system
      with a human AR multi-probe template set. Expression changes of 10 mRNAs of
      interest (AR, Rb, ARA160, ARA24, ARA54, ARA55, ARA70, BRCA1, F-SRC-1, and RAC3)
      were analyzed simultaneously as AR and AR-associated cofactors in 1 hybridization
      reaction. RESULTS: Seven of 10 cofactors tested were expressed in LNCaP cells.
      Only Rb, ARA55 and BRCA1 were not detected. LNCaP cells cultured in charcoal
      treated serum for 28 days clearly showed more than 1.5-fold increases in AR,
      ARA160, and ARA70 expression, while expression of ARA24 and ARA54 increased less
      than 1.5-fold. Only RAC3 and F-SRC-1 decreased in RNA expression. Cell morphology
      features changed gradually into neuron-like shapes with elongated cytoplasm
      during the culture period. Cell growth almost ceased 28 days after the start of
      culture. CONCLUSION: The changes in expression pattern of AR and AR cofactors and
      in particular the remarkable increase in AR, ARA160 and ARA70 support the role of
      AR cofactors in modulating prostate cancer cell growth from androgen dependence
      to androgen independence.

PMID- 16276441
TI  - Capsule endoscopy for gastrointestinal bleeding with an obscure etiology.
AB  - BACKGROUND AND PURPOSE: Capsule endoscopy (CE) is a new diagnostic modality that
      is being utilized with increasing frequency for examination of lesions suspected
      to be of small bowel origin. The most common indication for CE is obscure
      gastrointestinal bleeding. This study investigated the safety and diagnostic
      value of CE in patients with obscure gastrointestinal bleeding. METHODS: From
      February 1 to October 30, 2003, 35 patients with obscure gastrointestinal
      bleeding among 43 consecutive patients with suspected small bowel pathology were
      enrolled. The mean age of the patients was 50.5 years (range, 24-81 years). A
      negative panendoscopy and colonoscopic study were required for study eligibility.
      An M2A video capsule endoscope was swallowed by each patient after an overnight
      fast if plain abdominal radiograph done 1 day prior to the procedure was negative
      for obstruction. Bowel preparation using a mixed solution containing magnesium
      carbonate, citric acid anhydrous and potassium bicarbonate, and bisacodyl was
      performed only in selected patients. RESULTS: Abnormal findings were noted in 31
      of 35 patients (89%), 20 (57.2%) of whom had gastrointestinal pathology
      explaining their symptoms. Only 12 (34%) of the 20 patients had lesions solely in
      the small bowel. Angiodysplasia was the most common source of bleeding (37%),
      followed by Crohn's disease (14%). Other findings included Osler-Weber-Rendu's
      disease, gastrointestinal stromal tumor, vascular ectasia and small bowel
      diverticulum. Three capsules became lodged and did not provide images during
      subsequent transit through the colon, but serial abdominal plain radiographs done
      every 3 days after capsule ingestion showed passage of the capsules had occurred
      by 1 week. No discomfort or side effects were noted up to 2 months after
      ingestion. CONCLUSION: CE is a safe, painless and effective method for diagnosing
      obscure gastrointestinal bleeding. A final diagnosis was reached in more than one
      half of the patients and positively affected treatment. The capsule produced
      clear and recognizable images of lesions even without bowel preparation. If done
      early, CE can aid in directing proper management in patients with suspected small
      bowel pathology.

PMID- 16276442
TI  - Abdominal actinomycosis complicated with hydronephrosis.
AB  - Actinomycosis is a chronic supportive granulomatosis disease caused by the
      anaerobic Gram-positive organism Actinomyces. We report a 16-year-old boy with
      abdominal actinomycosis who presented with a 2-week history of intermittent
      abdominal pain. He complained of oliguria during the 3 days prior to admission.
      Abdominal computed tomography revealed a large inflammatory mass obstructing the
      ureter, which led to hydronephrosis of the right kidney. Exploratory laparotomy
      was performed and actinomycosis was confirmed by the presence of sulfur granules
      and filamentous bacteria. Postoperatively, the patient was successfully treated
      with long-term penicillin and recovered completely.

PMID- 16276443
TI  - Persistent pulmonary hypertension in a neonate with vein of Galen arteriovenous
      malformation.
AB  - Vein of Galen aneurysmal malformation (VGAM) often leads to death in the neonatal
      period, mainly due to congestive heart failure. Chronic and excessive pulmonary
      flow in utero and postnatally is attributed to large VGAM and right ventricular
      overload. We report a male neonate with VGAM complicated by severe heart failure
      and persistent pulmonary hypertension. Endovascular coil embolization of VGAM was
      performed, resulting in improvement of congestive heart failure; however, severe
      persistent pulmonary hypertension led to death 2 days after the embolization.
      Postmortem examination showed marked right and left ventricular hypertrophy and
      impressive muscular thickening of intra-alveolar arterioles. Neonatal
      embolization seems to be beneficial only in babies without suprasystemic
      pulmonary hypertension. Therefore, early delivery and repair of VGAM should be
      considered before the onset of persistent pulmonary hypertension.

PMID- 16276445
TI  - Extracorporeal membrane oxygenation support during repair of traumatic aortic
      transection.
AB  - Acute traumatic aortic transection is a critical condition in victims of major
      trauma. How to avoid the complications of surgical repair is still a challenge to
      trauma and cardiovascular surgeons. A 74-year-old woman was referred to our
      hospital with multiple fractures and hypotension after a motor vehicle accident.
      Computed tomography revealed acute traumatic aortic transection at the upper
      thoracic aorta with periaortic hematoma. She underwent repair of the aortic
      injury after primary survey. The patient received urgent aortic grafting under
      heparin-free extracorporeal membrane oxygenation support for lower body
      perfusion. The postoperative course was smooth. No neurologic or hemorrhagic
      complication was noted. The results of this case indicate that extracorporeal
      membrane oxygenation could be used as a heparin-free partial bypass system during
      surgery for traumatic aortic transection. The risk of spinal cord ischemia during
      aortic clamp or bleeding due to heparinization during conventional
      cardiopulmonary bypass could be minimized.

PMID- 16276444
TI  - Early detection of splenic metastasis of lung cancer by 18F-2-fluoro-2
      deoxyglucose positron emission tomography.
AB  - Diagnosis of splenic involvement by lung cancer in the early stage is helpful for
      introducing proper treatment. We report a case of pulmonary adenocarcinoma with
      splenic metastasis which was first detected by 18F-2-fluoro-2-deoxyglucose (18F
      FDG) positron emission tomography (PET). This 56-year-old male underwent left
      pneumonectomy, extensive lymph node dissection and postoperative adjuvant
      chemotherapy and radiotherapy. Because progressive elevation of carcinoembryonic
      antigen was detected 2 years after the operation, whole-body 18F-FDG PET was
      performed and revealed an 18F-FDG hypermetabolic spot in the splenic hilum.
      Although subsequent computed tomography (CT) did not reveal any lesions in the
      spleen, the second and third CT scans performed 10 and 13 months later confirmed
      the previous PET finding of splenic metastasis. This case suggests that 18F-FDG
      PET may be useful for early detection of splenic metastasis not visible on CT.

PMID- 16276446
TI  - Retroperitoneal venous hemangioma.
AB  - Venous hemangioma is an extremely uncommon tumor. We report a 61-year-old woman
      with a surgically proven venous hemangioma in the retroperitoneum. Image studies,
      including sonography, computed tomography and angiography, revealed a
      heterogeneous mass lesion with firm adherence to the adjacent organs and
      engulfing the major vessels. Only subtotal resection of the tumor was done due to
      technical difficulty. Follow-up magnetic resonance imaging 7 months after surgery
      showed reduction in size and much delayed enhancement of the residual tumor. In
      conclusion, firm attachment to adjacent organs and much delayed enhancement are
      clues for the diagnosis of a venous hemangioma.

PMID- 16276447
TI  - Effect of local anesthetic concentration on the anesthetic level in digital
      transthecal block.
AB  - Transthecal digital block is an effective anesthesia. The purpose of this study
      was to analyze the effect of different anesthetic concentrations on the
      anesthetic level of transthecal block. From July 2003 to August 2003, 17 patients
      with trigger finger received local anesthesia by transthecal digital block. The
      patients were randomized to receive either 1 mL 1% lidocaine and 0.5 mL
      betamethasone (7 mg/mL), or 1 mL 2% lidocaine and 0.5 mL betamethasone.
      Anesthetic intensity was checked over different aspects of digits. The 2%
      lidocaine group showed significantly better pain scores over the dorsal aspect of
      the digits (p = 0.002). The most effective anesthesia was in the volar aspect of
      the digits. Anesthesia was least effective in the dorsum of the digit at the
      lower anesthetic dose.

PMID- 16276448
TI  - [Recent advances in regional cerebral monitoring in the neurocritical patient:
      brain tissue oxygen pressure monitoring, cerebral microdialysis and near-infrared
      spectroscopy].
AB  - The long term outcome of head-injured patients depends not only on the primary
      brain lesions but also to a large extent on the secondary lesions. The diagnosis
      of many secondary lesions, and specially that of brain ischemia, is based on
      simultaneous monitoring of several intracranial and systemic variables.
      Continuous intracranial pressure (ICP) monitoring is currently considered
      indispensable in the management of all patients with a severe head injury and
      intracranial lesions. However, the information provided by this technique is
      insufficient to diagnose some of the complex physiopathological processes that
      characterize traumatic brain lesions. Consequently, the use of methods to
      estimate cerebral blood flow such as transcranial Doppler and jugular oximetry to
      complement ICP monitoring is becoming increasingly widespread. Nevertheless,
      determining the effect of tissue lesions and therapeutic measures on cerebral
      metabolism currently requires direct access to the brain parenchyma at the
      bedside. In this review we focus on three methods of regional cerebral
      monitoring: oxygen tissue pressure (PtiO(2)) monitoring, microdialysis and near
      infrared spectroscopy. The bases of each method and reference values for the
      variables analyzed will be discussed. We also make a series of recommendations on
      how results should be interpreted in light of current knowledge.

PMID- 16276449
TI  - [Effects of dexmedetomidine on intracranial hemodynamics in severe head injured
      patients].
AB  - Dexmedetomidine, an alpha 2 adrenergic agonist, with distinctive characteristics
      when compared to traditional plans, namely: conscious sedation, sympatholysis and
      lack of respiratory depression, represents an attempt to improve the
      sedoanalgesia of critically ill patients. OBJECTIVE. To study dexmedetomidine's
      effect on intracranial hemodynamic and hemometabolic parameters in severe head
      injured patients. MATERIAL AND METHODS. Prospective study on the effect of
      Dexmedetomidine on twelve severe head injured patients (Glasgow Coma Scale score
      <or= 8) admitted to an intensive care unit, with intracranial pressure < 20 mmHg
      and O(2) saturation monitoring of blood from jugular bulb. The drug was perfused
      intravenously during 3 hours, in progressive doses (0.2, 0.4 and 0.7 ug/kg/h).
      All other sedo-analgesia medication had been previously withdrawn. RESULTS. No
      significant differences were found in intracranial pressure, mean arterial
      pressure and cerebral hemometabolic parameters after infusion of dexmedetomidine
      in relation to basal values. Cerebral perfusion pressure showed a trend to
      decrease during the drug infusion (marginal effect, p =.058). Cardiac frequency
      decreased significantly after the drug administration. CONCLUSIONS. At the doses
      utilized, dexmedetomidine was safe, and it was not associated with significant
      changes in intracranial hemodynamics, nor in cerebral hemometabolic parameters,
      in a group of severe head jnjured patients.

PMID- 16276450
TI  - [Analysis of the lumbar discectomy complications].
AB  - OBJECTIVE: To analyze the complications in a series of patients operated on for
      lumbar disc herniations between 1997 and 2002. METHODS: The records of 64
      patients with the diagnosis of lumbar radicular compression by disc herniation
      who underwent 73 surgical procedures were analyzed. The patients with radicular
      pain without disc herniation were excluded. RESULTS: Complications occurring in 7
      cases (9.6 %) were 2 deep infections, 1 dural tear which was repaired, 2
      cerebrospinal fluid fistulae, 1 pseudomeningocele and 1 lesion of L5 root.
      CONCLUSIONS: - The most frequent complications were dural tear and infection.
      These observations are similar to those reported in previously published papers.

PMID- 16276451
TI  - [Percutaneous vertebral augmentation: vertebroplasty and kyphoplasty: operative
      technique].
AB  - The intravertebral injection of acrylic resin cement -usually
      polymethylmethacrylate (PMMA)- into a fractured vertebral body, constitutes the
      basis of the so called "vertebral augmentation techniques", "vertebroplasty" and
      "kyphoplasty", to manage pain and to strengthen and stabilize the compromised
      vertebra. In some ocassion, prior to the PMMA injection, an inflatable bone tamp
      was inserted into both pedicles of the fractured vertebra with the aim of
      restoring vertebral height to correct the kyphosis deformation. This procedure is
      called kyphoplasty (balloon-assisted vertebroplasty). The indications for
      vertebroplasty and kyphoplasty are evolving, from stabilization of painful
      osteoporotic vertebral fractures to vertebral collapse secondary to spinal
      metastases. In this paper we review the technical basis of both procedures,
      according to our experience in the treatment of vertebral fractures. Further
      studies are required to define the role for each technique in the spinal
      surgery's armamentarium.

PMID- 16276452
TI  - [Topographic anatomy of the asterion].
AB  - BACKGROUND: In the surgical approaches to the posterior fossa, the accurate
      location of the transverse-sigmoid sinus (TS-SS) complex is of great importance.
      The asterion is a referral landmark to the transverse sinus location. METHOD:
      Twenty-five skulls of adult cadavers were studied. We seek for the relationships
      of the asterion with: TS location, mastoid emissary vein, suprametal crest and
      inion. RESULTS: The asterion was found in 49 cases. In the great majority of
      cases (87.8%) the asterion was over the TS (72.2% over the sinus proper, 27.8%
      over the TS-SS transition). The mastoid emissary vein was present in 46 cases,
      and in 36% we found two veins. DISCUSSION AND CONCLUSIONS: The burr hole for
      posterolateral approaches to the posterior fossa must be located below and behind
      the asterion.

PMID- 16276453
TI  - [Spinal subarachnoid hematoma after lumbar puncture in a patient with leukemia:
      report of a case and review of the literature].
AB  - Acute myeloradicular compression due to a spinal subarachnoid hematoma (SSAH)
      after lumbar puncture (LP) is an extremely rare complication. Several risk
      factors have been involved in the production of these hematomas, mainly the
      presence of hemostasis disorders in the patient. We report the case of a 20-year
      old man with leukemia and thrombocytopenia (26,000 platelets/mm(3)) who, after
      undergoing a LP, developed paraparesis and became unable to stand. A magnetic
      resonance disclosed the presence of a ventral intradural hematoma from D12 to L4.
      An emergency decompressive laminectomy was performed and a hematoma located in
      the subarachnoid space was partially removed. On the fourth postoperative day,
      the patient was able to walk without assistance, but one month later, he died
      because of systemic complications of his disease. Only 26 cases of SSAH after LP
      have been found in the literature review we have performed. In most of them, the
      following common features have been observed: association with anticoagulant
      therapies, association with thrombocytopenia, delayed onset of compressive
      myeloradicular syndrome, need of surgical treatment, good functional outcome in
      half of patients, and short life expectancy for patients with previous serious
      illness. Risk for developing a SSAH after LP could be high in leukemia patients
      with a tendency to have severe thrombocytopenia (perhaps less than 25,000
      platelets/mm(3)).

PMID- 16276455
TI  - Demographics of hemophilia in developing countries.
AB  - Demographic datasets pertaining to populations are extremely valuable tools in
      healthcare planning. They are vital in setting priorities, allocation of
      resources, measurement of outcomes, and comparison of alternate approaches.
      Countries with emerging economies especially need information regarding targeted
      populations when initiating programs designed to deliver care to persons with
      chronic conditions such as hemophilia. The problems associated with data
      collection in these countries are huge but surmountable. The World Federation of
      Haemophilia (WFH) Global Survey provides a valuable synopsis of current global
      data on hemophilia patients and has provided insight into the extent of the
      problem with hemophilia worldwide. More and more countries recognize the uses of
      these data and have established or are in the process of establishing registries
      for persons with hemophilia to try and improve the quality of the information
      provided to the WFH. This information will most certainly assist in guiding the
      future of hemophilia care in these countries with emerging economies.

PMID- 16276457
TI  - Management of hemophilia with minimal factor replacement in developing countries:
      role of ancillary therapy.
AB  - Compared with developed countries, the care of hemophiliacs in still relatively
      poor in developing countries. There are three major factors that influence this
      problem: inadequate knowledge, lack of laboratories to diagnose the disorder, and
      inadequate supply of factor concentrates. It is important that healthcare
      providers and family members of these patients be adequately educated about all
      of the aspects of hemophilia. Basic laboratories could be established at a
      reasonable price, technical personnel could be trained, and quality-assurance
      programs could be initiated. Even in the absence of high-quality factor
      concentrates, which are expensive, there are affordable means to manage these
      patients, although certainly not optimally. To overcome these problems,
      hemophilia care services need to be established and integrated to facilitate the
      basic needs for these patients.

PMID- 16276456
TI  - Hemophilia treatment in developing countries: products and protocols.
AB  - The most important aspect of management of hemophilia is to provide adequate
      replacement of safe clotting factor concentrates to prevent or treat bleeding
      episodes. There has been considerable progress in many countries in the
      developing world with regard to this aspect of care. However, very little data
      are available in the literature on the types of products being used for factor
      replacement and the doses being administered for control or treatment of bleeding
      in different countries. These data are important to document because only then
      can data from different centers be compared. This article provides data from
      seven countries: Korea, Malaysia, Thailand, Venezuela, Argentina, Iran, and
      India. It shows that there is wide variability not only in the types of products
      used (plasma to recombinant factor concentrates) but also in the doses
      administered (minimal to very high) for similar indications. Prospective
      documentation of data on musculoskeletal outcome at these centers and correlation
      with dose of factor replacement could help identify different models of care.
      Comparing such data and collating the experience in different countries could be
      useful for optimizing care and establishing cost-effective models. The combined
      experience in the developing world in providing hemophilia services should be
      used to define standards of care that are practical and to set achievable goals.

PMID- 16276458
TI  - Products for clotting factor replacement in developing countries.
AB  - Developing countries provide clotting factor replacement for hemophilia patients
      using one or more of the following strategies. (1) Production of domestic plasma
      and cryoprecipitate provides some self-sufficiency but depends heavily on the
      presence of an excellent blood transfusion service. The risk of transmitting
      donor infections is not completely obviated even with good serologic testing. (2)
      Domestic plasma fractionation has been achieved in a handful of emerging
      countries but can be expensive. Patients may distrust businessmen of their own
      country and may be dissatisfied with the style of product available from domestic
      plants. (3) Contract fractionation has been successful when the donor country is
      able to provide adequate amounts of well-tested plasma. Its cost is not always
      lower than that of imported concentrate but a degree of national self-sufficiency
      is retained. (4) Importation of concentrate allows a wide choice of products. The
      selection should focus not only on price but also on product safety, which
      depends upon well-validated donor testing and viral inactivation. High levels of
      purification are not of great importance. Successful national hemophilia programs
      also address organization of care, sensible dosing, and equitable distribution of
      resources to gain the maximum benefit from scarce resources.

PMID- 16276459
TI  - The role of physical therapy and rehabilitation in the management of hemophilia
      in developing countries.
AB  - Without replacement therapy, patients with severe hemophilia (PWH) will have five
      damaged joints by the age of 20, which lead to limitation of activities and
      prevent normal participation in society. Of all PWH, 80% live in developing
      countries, where access to factor replacement is limited. Physiotherapy and
      rehabilitation help to prevent disabilities, stimulate activities and
      participation, and help to preserve autonomy. Rehabilitation should be organized
      by creating awareness that physiotherapy and rehabilitation (next to availability
      of safe clotting factor) are very important in developing countries. Locally
      available medical and social systems and materials should be used for both
      education and aids and adaptations. Trainers must be trained to develop local
      treatment protocols. PWH and their families need to be educated and trained to do
      exercises. Important treatment modalities are management of pain, active muscle
      strengthening exercises, combined measures and exercises to regain range of
      motion, training proprioception and coordination, functional training, and
      orthotics and shoe adaptations.

PMID- 16276460
TI  - Hemophilia orthopedic management with emphasis on developing countries.
AB  - The articular problems of patients with hemophilia begin in infancy when minor
      injuries result in hemarthroses. Early continuous prophylaxis (from cradle to
      college) is of paramount importance because the immature skeleton is very
      sensitive to the complications of hemophilia; severe structural deficiencies may
      develop quickly. If continuous prophylaxis is not feasible owing to the expense
      of the clotting material or lack of venous access, then a major hemarthrosis must
      be treated aggressively to prevent the development of synovitis, recurrent joint
      bleeds, and ultimately end-stage arthritis. Once synovitis has developed, which
      bleeding will make inevitable, the aim should be to treat it as soon as possible.
      There are conservative (synoviorthesis) and operative (open or arthroscopic
      synovectomy) methods. Between the second and fourth decades, many patients with
      hemophilia develop articular complications. Once this has occurred, treatment
      modalities such as alignment osteotomies, joint debridement, arthrodesis, and
      arthroplasties are possible. Should surgery be required, one should consider
      multiple procedures.

PMID- 16276461
TI  - Transfusion-transmitted infection in hemophilia in developing countries.
AB  - Treatment of patients with bleeding disorders (especially those with hemophilia)
      with blood products has been associated with infections with blood-borne viruses.
      Of these, hepatitis B and C viruses (HBV and HCV, respectively) and the human
      immunodeficiency virus (HIV) have created major health problems. Although virus
      inactivation procedures have virtually eliminated these viruses from newer factor
      concentrates since 1985, the risk remains in developing countries where there is
      no ready access to these concentrates. Although a few of these countries have
      established their own fractionation facilities and in others the respective
      governments make concentrates available, the large majority of countries still
      face the problems of blood-borne infections. HCV will invariably lead to liver
      damage and many hemophiliacs who were exposed to the HCV virus will succumb to
      cirrhosis. Only approximately 10% of hemophilic patients infected with HCV will
      clear the infection naturally. Coinfection with HIV shortens the life expectancy.
      The HIV epidemic in hemophiliacs began in the mid-1980s. Patients in developed
      countries were especially affected because they were predominantly treated with
      factor concentrates that were manufactured from thousands of blood donors.
      Hemophiliacs in developing countries have considerably less HIV infection,
      although it does exist and depends largely on the source of the plasma fractions.
      Progress has been made not only in the purification of factor concentrates, but
      also in the understanding of the HIV virus and in the development of
      antiretroviral treatment modalities. However, there are still several challenges
      in delivering antiretroviral treatment that must be addressed before the full
      impact of these transmitted infections is known.

PMID- 16276462
TI  - Surgery for hemophilia in developing countries.
AB  - Surgical interventions in patients with hemophilia (PWH) in the developing world
      are difficult in the setting of limited availability of factor concentrates.
      Although the adequacy of international guidelines for factor concentrate
      prophylaxis for PWH undergoing surgery has been established, frequently it is not
      practical in the developing world. These recommendations were not established
      based on large clinical trials and fail to define the safe lower limit of factor
      concentrate prophylaxis for surgery. The need to define these lower limits is
      essential in the developing world so that the limited resources may be used
      optimally for the cohort of PWH. There are limited data from the developing world
      with regard to PWH undergoing surgical procedures. In this article, we outline
      experience from our institution, a tertiary referral center for hemophilia care
      in India. We trace the basis on which our current factor concentrate prophylaxis
      regimen (which is lower than that recommended internationally) was established.
      In our experience our low-dose protocols are effective, reduce factor consumption
      by one third, and are not associated with a significantly increased risk of
      delayed hemorrhage. We hope that this experience will form a framework on which
      guidelines can be established for developing countries.

PMID- 16276464
TI  - World Federation of Haemophilia programs in developing countries.
AB  - The World Federation of Haemophilia (WFH) is a global not-for-profit organization
      devoted to furthering the treatment of hemophilia and related disorders. Founded
      in Montreal in 1963, it has grown tremendously during the last 40 years and now
      has 107 National Member Organizations and has been recognized by the World Health
      Organization. The mission of the WFH is to introduce, improve, and maintain care
      for patients with hemophilia and related disorders. Several specific programs may
      be used as tools to achieve these goals. The WFH organizes regular educational
      workshops on key aspects of hemophilia care. Fellowships are offered to
      approximately 30 healthcare professionals each year that provide funding for a
      period of study of up to 8 weeks at an International Hemophilia Training Center
      of their choice. The WFH twinning program helps emerging hemophilia treatment
      centers develop partnerships with well-established centers. Although the ultimate
      goal of the WFH is to promote sustainable hemophilia treatment in developing
      countries, donations of concentrate are regularly made through the Humanitarian
      Aid program. The WHF launched the Global Alliance for Progress in its 40th
      anniversary year, establishing a partnership between the WFH and other
      stakeholders, including the pharmaceutical industry. The aim is to focus on 30 to
      40 developing countries during the next 10 years, aiming to more than double the
      number of patients diagnosed with hemophilia in those countries. The WFH is also
      involved in fostering discussion on key issues such as safety and supply of blood
      products.

PMID- 16276463
TI  - Carrier detection and prenatal diagnosis of hemophilia in developing countries.
AB  - Hemophilia A and B, inherited as X-linked recessive traits, are the most common
      hereditary hemorrhagic disorders caused by a deficiency or dysfunction of
      coagulation factor VIII (FVIII) or FIX, respectively. Hemophilia is prevalent
      worldwide, without ethnic or geographic limitations, and remains a life
      threatening and often disabling condition. Advances in molecular medicine in this
      century have markedly improved hemophilia treatment. However, management is still
      largely inadequate in developing countries. Therefore, carrier detection and
      prenatal diagnosis remain the key steps for the prevention of the birth of
      children with hemophilia in developing countries where patients with this
      coagulation disorder rarely live beyond childhood. Carrier detection and prenatal
      diagnosis are possible by direct or indirect genetic analysis of the F8 or F9
      genes. In countries with more advanced molecular facilities and higher budget
      resources, the most appropriate choice in general is a direct strategy for
      mutation detection by prescreening techniques or direct mutation detection.
      However, in countries with limited facilities and low budget resources, carrier
      detection and prenatal diagnosis are usually performed by linkage analysis with
      genetic markers. This article suggests the possibilities of genetic diagnosis and
      a feasible strategy for carrier detection and prenatal diagnosis in families with
      hemophilia A and B in developing countries.

PMID- 16276465
TI  - Expanding hemophilia care in developing countries.
AB  - The World Federation of Haemophilia (WFH) estimates that worldwide, approximately
      70% of patients with hemophilia are underdiagnosed and untreated. Most live in
      developing countries. Although in developed countries the life expectancy of
      hemophiliacs is close to that of healthy persons, this is not the case in
      developing countries. Great disparity also exists in the treatment of
      hemophiliacs, especially when this relates to available factor concentrates.
      There are many reasons for the inadequate care of hemophilic patients: the
      perception of rarity of the disease; lack of laboratory facilities to diagnose
      the disorder; lack of understanding of the disorder by patients, their relatives,
      and even healthcare providers; poorly developed blood bank facilities; and lack
      of adequate factor supply are just some examples. The WFH attempts to address
      many of these issues by establishing hemophilia care programs and by educating
      and training healthcare practitioners so that a healthcare team can be organized
      that attempts to ameliorate these problems and provides treatment options. In the
      last few years, a considerable number of developing countries have been organized
      to deliver at least a minimum of care, and attempts have been made to obtain
      support from appropriate governmental sources.

PMID- 16276466
TI  - Epidemiology of von Willebrand disease in developing countries.
AB  - There is limited information on von Willebrand disease (vWD) in developing
      countries. A questionnaire survey in 1998 showed that overall, less than one
      third of the expected number of patients with vWD in the population had been
      detected. Among those registered, the proportion with the severe form of the
      disease was relatively higher, forming up to 50% of the total, particularly in
      those countries with high prevalence of consanguineous marriages. Diagnosis was
      based on von Willebrand factor antigen (vWF:Ag) assays, vWF ristocetin cofactor
      (vWF:Rco) activity, and ristocetin-induced platelet aggregation (RIPA) at the
      reporting centers, but vWF multimer analysis was not widely available.
      Responsiveness to desmopressin acetate (DDAVP), which could be very significant
      clinically, was not often assessed. An attempt was made to assess accuracy of
      reporting of the prevalence of vWD by conducting a second survey aimed at
      normalizing the reported numbers with that of severe hemophilia A in a defined
      population on the presumption that the latter is less likely to be missed. These
      data showed that in most countries, the ratio of patients with vWD to severe
      hemophilia varied between 0.1 to 0.6 with a mean of approximately 0.4, as opposed
      to an expected ratio of approximately 1 (based on population-based data from
      Italy), confirming the underdiagnosis of vWD even within the same health-care
      system. A system for collecting more extensive and detailed data on vWD from
      developing countries (where 80% of the world's population lives) is required.
      Efforts are needed to develop national registries and make at least basic
      services for diagnosis and treatment widely available.

PMID- 16276467
TI  - Characterization, classification, and treatment of von Willebrand diseases: a
      critical appraisal of the literature and personal experiences.
AB  - Recessive type 3 von Willebrand disease (vWD) is a severe hemophilia-like
      bleeding disorder caused by homozygosity or double heterozygosity for two
      nonsense mutations (null alleles) and characterized by a strongly prolonged
      bleeding time (BT), absence of ristocetin-induced platelet aggregation (RIPA),
      absence of von Willebrand factor (vWF) protein, and prolonged activated partial
      thromboplastin time (APTT) due to factor VIII (FVIIIC): deficiency. Recessive
      severe type 1 vWD is caused by homozygosity or double heterozygosity for a
      missense mutation and differs from type 3 vWD by the detectable presence
      vWF:antigen (Ag) and FVIII:C levels between 0.09 and 0.40 U/mL. Carriers of one
      null allele or missense mutations are usually asymptomatic at vWF levels of 50%
      of normal. Mild recessive type 1 vWD may be due to a missense mutations, or one
      missense mutation plus blood group O. The so-called dominant type 1 vWD secretion
      defect and type 1 Vicenza are caused by a heterozygous missense mutation in the
      vWF gene that produces a mutant vWF protein having a dominant effect on the
      normal vWF protein produced by the normal vWF allele with regard to the defective
      processing, storage secretion, and/or proteolysis of vWF in endothelial cells and
      clearing from plasma consistent with a type 2 phenotype of vWD. Typical type 2
      vWD patients, except 2N, show a defective vWF protein, decreased ratios for
      vWF:ristocetin cofactor [vWF:RCo]/vWF:Ag and vWF:collagen binding factor
      [vWF:CB]/vWF:Ag and prolonged BT. The BT is normal and FVIII:C levels clearly are
      lower than vWF:Ag in type 2N vWD. Multimeric analysis of vWF in plasma
      demonstrates that proteolysis of vWF is increased in type 2A and 2B vWD, with
      increased triplet structure of each band (not present in types 2M and 2U).
      Proteolysis of vWF is minimal in type 2C, 2D, and 2E variants that show aberrant
      multimeric structure of individual oligomers. vWD 2B differs from 2A by normal
      vWF in platelets, and increased RIPA. RIPA is normal in mild, decreased in
      moderate, and absent in severe type 2A vWD. RIPA is decreased or absent in 2M,
      2U, 2C, and 2D; variable in 2E; and normal in 2N and dominant type 1. vWD 2M is
      usually mild and features decreased vWF:RCo and RIPA, and a normal or near-normal
      vWF multimeric pattern in a low-resolution agarose gel. vWD 2A-like or
      unclassifiable (2U) is distinct from 2A and 2B and typically features low vWF:RCo
      and RIPA with the relative lack of large vWF multimers. vWD type 2C is recessive;
      the dominant type 2D is rare. The response to desmopressin acetate (DDAVP) of vWF
      parameters is normal in pseudo-vWD and mild type 1. The responses to DDAVP of
      FVIII:C and vWF parameters in vWD 2M, Vincenza, 2E, and mild 2A, 2U, and 2N are
      transiently good for a variable number of hours to arrest mucocutaneous bleeding
      episodes or to prevent bleeding during minor surgery or trauma. However, the
      responses are not good enough to treat major bleedings or to prevent bleeding
      during major surgery or trauma. The response to DDAVP of vWF parameters is poor
      in recessive type 3, 1 and 2C, and dominant 2A, 2B, and 2U. Proper
      recommendations of FVIII/vWF concentrates using FVIII:C and vWF:RCo unit dosing
      for the prophylaxis and treatment of bleeding episodes in type 2 disease that is
      nonresponsive to DDAVP and in type 3 vWD are proposed.

PMID- 16276468
TI  - Management of von Willebrand disease in developing countries.
AB  - A variety of treatment options are available at present for patients with von
      Willebrand disease (vWD), some of which are affordable for patients in developing
      countries. For most patients who have type 1 vWD, desmopressin acetate (DDAVP) is
      the treatment of first choice, at least for minor bleedings and for prophylaxis.
      It is advisable, however, to use a test dose first to note the patient's
      response. DDAVP is safe to use, affordable, and easy to administer. However, most
      patients with type 2 vWD and all patients with type 3 fail to respond to DDAVP.
      For these patients, other options are used. Almost all patients with vWD will
      benefit from fresh frozen plasma and from cryoprecipitate, and these are viable
      options for developing countries. Both have certain disadvantages, but they can,
      depending upon the circumstances and facilities, be produced in developing
      countries. In developed countries, factor VIII/von Willebrand factor concentrates
      are widely used, especially for major bleedings and for surgeries on these
      patients. These concentrates are safe and virus inactivated, but costly.
      Ancillary treatment modalities such as antifibrinolytic agents and certain
      hormones are usually given in conjunction with other modalities. The treatment of
      patients with antibodies to vWF is also described, and monitoring needs during
      therapy are reviewed.

PMID- 16276469
TI  - On "the P2 receptors and congenital platelet function defects" (Semin Thromb
      Hemost 2005;31:168-173).

PMID- 16276470
TI  - [Geriatric urology -- incontinence in the elderly].
AB  - Urinary incontinence is a major problem in elderly patients. Severe
      underreporting of symptoms in combination with a reluctance of health
      professionals to ask about continence problems lead to a relevant illness burden.
      Individual psychological distress and reduction in self-perceived quality of life
      ending in social isolation cause significant subsequent morbidity. Therefore
      active case finding for continence-problems is an important obligation for health
      care providers, since effective pharmacological, non-pharmacological and surgical
      treatment-options are available. A combination of different therapeutic
      modalities often leads to an appreciable improvement of the symptoms, and
      sometimes a cure even in old patients. Therapeutic options and prognosis of
      different treatment approaches should be discussed in an unbiased manner with
      patients.

PMID- 16276471
TI  - [Teaching outpatient medicine at urological congresses].
AB  - In Germany there is a two-track system for treatment of patients by specialists:
      severe diseases are treated in hospitals, less severe ones in outpatient
      practices/physicians' offices. Further training of specialist physicians must
      take both points of view into consideration. This task is not easy because
      specialists from university are most suitable as teachers, but they seldom have
      their own experience with the patients in outpatient offices (Praxis) and their
      less severe problems. The aim of this investigation was carry out an analysis of
      relevant structures, to improve them and to develop a new kind of further
      training. Our own data quantify the differences between these institutions with
      regard to the severity of the disease and the diagnosis. Topics of outpatient
      medicine are insufficiently represented in traditional congresses and doctors
      with outpatient practices too seldom take part in these congresses. They were
      questioned about their wishes with regard to topics of training/education,
      suitable dates and organisational structures. Practicing urologists expressed a
      desire for science and hints for outpatient medicine, organised in the form of
      seminars. Our way to organise such seminars, planned and conducted by urologists
      in outpatient practices is described and discussed and we report our experience.

PMID- 16276472
TI  - [Relevance of intraoperative frozen section diagnostics in urological surgery].
AB  - Intraoperative frozen section diagnosis (FSD) plays an important role in
      urological surgery. The surgeon obtains information on suspicious tissue and can
      adapt his strategy for the operation, thus sparing the patient from a second
      intervention. Most important for a successful FSD is close co-operation between
      the urologist and an experienced pathologist. A very reliable assessment of
      urological tissues can be made with the help of FSD. The same applies for the
      margin status of tumours, which is most important for example in renal tumour
      enucleation to achieve the same oncological result as with a radical tumour
      nephrectomy. For the diagnosis of lymph nodes the indication for FSD depends on
      the urological primary lesion. Especially for prostate cancers some authors
      rather recommend the evaluation of the nodal status according to nomograms. FSD
      for "sentinel nodes" is promising but has not yet found its way into routine
      diagnostics.

PMID- 16276473
TI  - [Rupture of the spleen and acute pancreatitis after ESWL therapy: a rare
      complication].
AB  - INTRODUCTION: ESWL is a safe and efficient method in the therapy of urolithiasis
      which, however, is not free of complications. CASE REPORT: ESWL was performed in
      a 54-year-old patient with a stone of 18 mm in size located in one of the upper
      calyces of the left kidney. Several hours after the ambulatory ESWL treatment the
      patient was admitted to the emergency room with strong pain in the left lumbar
      region and the upper abdomen. During examination low blood pressure, tachycardia
      and low Hb levels were found. Ultrasound and CAT scans revealed a subcapsular
      rupture of the spleen. Surgery was indicated, and a laparotomy with splenectomy
      was performed. Ten days after surgery the patient developed acute pancreatitis
      which was treated conservatively with success. CONCLUSIONS: Although ESWL is a
      safe method in the treatment of urinary stones with a relatively small number of
      complications, rare complications like ruptures of the spleen have to be
      considered. Special attention should be given to patients with kidney stones in
      the left upper calyces, pathological growth of the spleen, and accompanying
      diseases such as chronic heart failure or hypertension. In such patients ESWL
      should not be performed on an outpatient basis.

PMID- 16276474
TI  - [Ureteroiliac artery fistula -- a rare cause of macroscopic haematuria].
AB  - INTRODUCTION: Since its first description in 1939 not more than approximately 80
      cases of ureteroiliac artery fistulas have been reported. The incidence seems to
      increase with the number of endo-vascular and endo-urological interventions. Risk
      factors include pelvic vascular surgery and surgery for malignancy, irradiation
      and ureteral stenting. Due to the intermittent symptomatology, the preoperative
      diagnosis and planning of the therapeutic approach are often difficult. CASE
      REPORT: We report the case of an ureteroiliac artery fistula caused by an iliac
      artery aneurysm following vascular surgery, and review the literature.
      CONCLUSIONS: In case of preoperative diagnosis it is of great importance to
      coordinate the cooperation of urologists, vascular surgeons and radiologists in
      order to achieve the best treatment for the patient.

PMID- 16276475
TI  - [Vesicovaginal fistulas: transperitoneal surgical repair using omentum or
      peritoneal tissue interposition, vaginal repair using Martius flaps].

PMID- 16276476
TI  - [Correlation between psychosocial factors and periodontal disease--a systematic
      review of the literature].
AB  - OBJECTIVES: This is a systematic review of the available empirical studies up to
      2004 which deal with the question of the correlation between psychosocial
      factors/stress and gingival and periodontal disease. METHOD: The three medical
      and psychological databases Medline, PsycInfo und Psyndex were searched
      systematically for relevant literature between 1946 and 2004. RESULTS: 34
      empirical studies on humans (16 with and 18 without a control group) and ten
      empirical studies on animals are presented. DISCUSSION: Despite serious
      methodological flaws in many studies, most (particularly the methodologically
      solid ones) indicated associations between a variety of psychosocial factors and
      periodontitis incidence and severity. The pathomechanisms between stress and
      periodontitis should therefore be the subject of further research.

PMID- 16276477
TI  - [Psychological motives behind the wish to have children among High School and
      University students under consideration of female test persons with eating
      disorders].
AB  - OBJECTIVES: The aim was to investigate psychological motives behind the wish to
      have children among female and male students, with special consideration of
      females with eating disorders. METHODS: 736 participants (437 women and 299 men)
      were examined using the "Leipziger Fragebogen zu Kinderwunschmotiven und
      Einstellungen zum Kinderwunsch" (a questionnaire concerning the motives and
      attitudes for the wish to have a child). Disturbed eating behaviour was
      classified with the Eating Attitudes Test. RESULTS: 15.4 % of the students showed
      a low, 39 % a medium and 45.6 % a high wish to have children. The subscales
      "Desire for emotional stabilization" as well as "Social stereotypes" had the
      highest and "Fear of material impairment" and "Personal restriction" the lowest
      correlation with the wish for a child. Women with anorectic eating disorders
      displayed a significantly lower desire for children than students with normal
      eating patterns or women with a bulimic tendency. CONCLUSIONS: The psychological
      motives examined here contributed highly to the explanation of variance
      concerning the wish to have children. The results for women with eating disorders
      indicate that primary ambivalences concerning the wish to have children may be
      involved in the pre-clinical stadium of eating disorders.

PMID- 16276478
TI  - [Psychological comorbidity in subacute and chronic tinnitus outpatients].
AB  - OBJECTIVES: The aim of the study is to assess psychosomatic symptoms and
      comorbidity in a group of tinnitus out-patients and their correlation with
      tinnitus distress. METHODS: 32 subacute (duration 3-12 months) and 71 chronic
      tinnitus patients participated in the study. Questionnaires were used to assess
      tinnitus distress (German version of the TQ, VAS), psychosomatic symptoms (SCL-90
      R, BDI, BAI) coping strategies (KKG, FKV), social support (F-SOZU) and
      interpersonal problems (IIP-D). RESULTS: 56 % of subjects met the criteria for a
      disorder according to DSM-IV (CIDI). Compared to the general population, there is
      a particularly high comorbidity with anxiety and somatoform disorders. Tinnitus
      distress was related to depression (BDI), tinnitus loudness and disturbance of
      activities (59 % explained variance). There were no substantial differences
      between subacute and chronic tinnitus. CONCLUSIONS: The results stress the
      importance of diagnostic investigation of comorbidity and psychosomatic symptoms
      already at the subacute stage in tinnitus patients.

PMID- 16276480
TI  - On the significance of CD8 alpha alpha expression for T cell memory.
AB  - Longitudinal studies on the kinetics of viral antigen specific CD8 T cell
      responses have led to a model whereby a relatively small subset of the primary
      effector CD8 T cells expanding after the first week of acute viral infection
      initiate a program of cell survival and differentiation into long lived memory T
      cells. These T cells are then critical for maintaining protective immunity to
      subsequent viral infection. Recent observations, using fluorescent tetramers of
      the MHC class Ib molecule TL, link transient expression of CD8alphaalpha
      homodimers on expanding primary effector CD8 T cells to the generation of memory
      cells. At present it is controversial what the role of CD8alphaalpha is in the
      generation of memory CD8 T cells. The involvement of the high affinity
      CD8alphaalpha ligand, the TL molecule, is not understood either. However,
      evidence from two viral infection models in mice, including one paper in this
      issue of the European Journal of Immunology, suggest a role for CD8alphaalpha in
      this process and call for additional research focus into these issues.

PMID- 16276481
TI  - Linking stress, oxidation and the chemokine system.
AB  - Experimental evidence has shown that the chemokine system is redox-regulated, but
      little is known about the molecular mechanisms involved. IL-8/CXCL8 is a
      neutrophil chemotactic protein that characterizes the inflammatory reaction in
      many pathological conditions. Accordingly, pro-inflammatory agonists and oxygen
      radicals induce IL-8. In the current issue of the European Journal of Immunology,
      Rovin and colleagues report that IL-8 can be produced by mesangial and
      endothelial cells through a redox-regulated, namely Nfr2-dependent, pathway. This
      finding is somewhat surprising as IL-8 is not a stress or detoxifying protein,
      nor an antioxidant. This therefore suggests an additional role for the
      transcription factor Nrf2 in the regulation of inflammation and provides some
      insights into the molecular mechanisms.

PMID- 16276482
TI  - Decreased CD4 expression by polarized T helper 2 cells contributes to suboptimal
      TCR-induced phosphorylation and reduced Ca2+ signaling.
AB  - Polarized Th1 and Th2 cells expressing the same TCR produce distinct biochemical
      responses to ligand engagement. Compared to Th1 cells, Th2 cells show altered
      substrate tyrosine phosphorylation and a diminished or transient Ca2+ response.
      Here we demonstrate that agonist stimulation of Th1 cells leads to the
      predominant appearance of fully phosphorylated (p23) TCR zeta, substantial
      phosphorylation of zeta-associated protein 70 (ZAP-70), and strong elevation of
      intracellular Ca2+, whereas agonist stimulation of Th2 cells expressing an
      identical TCR results in an elevated p21:p23 TCR zeta ratio, little or no
      detectable ZAP-70 phosphorylation, and a more limited elevation in intracellular
      Ca2+. Th2 cells consistently had twofold lower surface CD4 expression as compared
      to Th1 cells with the same TCR. When CD4 levels in Th2 cells were raised to Th1
      levels using retroviral gene transfer, the transduced cells showed greater
      generation of p23 phospho-zeta, measurable phosphorylation of ZAP-70, and
      increased Ca2+ responses. These findings suggest that the apparent qualitative
      differences in TCR signaling characterizing Th1 versus Th2 cells are largely the
      result of modest quantitative variation in CD4 expression, with decreased CD4
      expression playing a significant role in attenuating the proximal signaling
      responsiveness of Th2 cells to TCR ligands.

PMID- 16276483
TI  - Lack of antigen-specific Th1 response alters granuloma formation and composition
      in Schistosoma mansoni-infected MyD88-/- mice.
AB  - To evaluate the role of the innate immune system during schistosomiasis in vivo,
      we infected myeloid differentiation factor 88 (MyD88)-deficient mice with
      Schistosoma mansoni and analyzed their pathognomonic formation of hepatic
      granulomas and T cell responses. Even though the differences between knockout and
      wild-type mice in terms of mortality, liver damage, serum IgE and parasite burden
      were insignificant, the liver granulomas in the MyD88-deficient mice were
      significantly smaller, less cellular and contained a reduced percentage of
      eosinophils. Histologically, these granulomas revealed stronger fibrosis,
      confirmed also by increased levels of soluble collagen and IL-13, implying a Th2
      bias. Spleen cells from infected MyD88-deficient mice also produced significantly
      less IFN-gamma than their wild-type controls upon restimulation with Schistosoma
      egg-antigen (SEA). Furthermore, SEA-loaded APC from naive wild-type or MyD88
      deficient mice induced equal amounts of proliferation and cytokine secretion by T
      cells from wild-type infected mice. In contrast, Ag-specific T cells from
      infected MyD88-deficient mice produced hardly any IFN-gamma but considerably more
      IL-10, again regardless of the APC type. These findings indicate that the loss of
      IFN-gamma production is not due to impaired antigen presentation but may perhaps
      is due to suppression by IL-10-producing T cells. Thus, MyD88 plays an important
      role in cellular infiltration, granuloma composition and T cell responses during
      schistosomiasis.

PMID- 16276485
TI  - Electrospray tandem mass spectrometry of underivatised acetylated xylo
      oligosaccharides.
AB  - Acetylated neutral (Xyl(n)Ac(m)) and acidic xylo-oligosaccharides
      (Xyl(n)Ac(m)MeGlcA, and Xyl(n)Ac(m)MeGlcAHex) obtained by partial acid hydrolysis
      of Eucalyptus globulus wood glucuronoxylans and fractionated by preparative
      ligand exchange/size-exclusion chromatography were identified by electrospray
      ionisation mass spectrometry (ESI-MS). Low molecular weight acetylated xylo
      oligosaccharides were studied by ESI-tandem mass spectrometry (MS/MS). All the
      acetylated xylo-oligosaccharides showed an abundant ion due to the neutral loss
      of 60 Da (CH(3)CO(2)H) in the MS/MS spectra. The presence of diacetylated xylo
      oligosaccharides was confirmed by the ions formed by loss of two molecules of
      acetic acid. Furthermore, characteristic [Xyl(res)Ac(2)+Na](+) and
      [XylAc(2)+Na](+) ions, and ions due to loss of XylAc(2), indicate that both
      acetyl groups are located in the same Xyl residue. On the other hand, losses of
      Xyl(res)Ac and XylAc are also observed as well as [Xyl(res)Ac+Na](+) and
      [XylAc+Na](+) , indicating the location of both acetyl groups in different Xyl
      residues, in some cases even in adjacent xyloses. The MS/MS spectra of
      triacetylated xylo-oligosaccharides were complex due to the presence of different
      isobaric xylo-oligosaccharides containing the acetyl groups at different
      locations in the xylo-oligosaccharide backbone. In the MS/MS spectra of acidic
      xylo-oligosaccharides, the ion at m/z 387, [Xyl(res)AcMeGlcA+Na](+), indicates
      that the acetyl groups are preferentially linked to Xyl substituted with MeGlcA.
      However, acidic xylo-oligosaccharides with the acetyl and 4-O-methylglucuronic
      acid groups in different Xyl residues were also identified. In neutral and in
      acidic xylo-oligosaccharides several possible locations of the acetyl groups were
      identified, namely at terminal positions. In summary, ESI-MS/MS is shown to be a
      powerful tool for the characterisation of acetylated patterns in complex mixtures
      of oligosaccharides.

PMID- 16276484
TI  - Reduced thymic output, increased spontaneous apoptosis and oligoclonal B cells in
      polyethylene glycol-adenosine deaminase-treated patients.
AB  - Impairment of purine metabolism due to adenosine deaminase (ADA) deficiency is
      associated with a severe combined immunodeficiency (SCID). Polyethylene glycol
      modified ADA (PEG-ADA) has provided noncurative, life-saving treatment for these
      patients, but full immune recovery is not achieved with this therapy. Since ADA
      SCID is perhaps the most difficult form of SCID to handle clinically,
      understanding the benefits and limitations of PEG-ADA therapy may be relevant for
      treatment selection. To this purpose, we analyzed the rate of thymic output, T
      and B cell repertoires, number of T cell divisions, IFN-gamma and IL-4
      production, and the extent of cell death in five ADA-SCID patients following a
      prolonged period of treatment with PEG-ADA. We found that thymic output was low
      in these patients. However, their T cell repertoire was heterogeneous, and their
      T lymphocytes produced cytokines upon activation and responded to mitogen
      stimulation, although with different kinetics. Furthermore, a high number of
      peripheral T lymphocytes were committed to apoptosis. Anomalies were also
      observed in the B cell compartment, with oligoclonal expansions of B cell
      clonotypes in two patients. Our data indicate that decreased thymic function, B
      cell oligoclonality, and increased spontaneous apoptosis may be the mechanisms by
      which the immunodeficiency of ADA-SCID patients persists in spite of treatment
      with PEG-ADA.

PMID- 16276486
TI  - Large-scale identification of human biliary proteins from a cholesterol stone
      patient using a proteomic approach.
AB  - Gallbladder bile, one of the most important body fluids, is composed of water,
      inorganic ions, conjugated bile salts, phospholipids, cholesterol, bilirubin,
      mucin and proteins. The separation and identification of bile proteins remain
      difficult due to the complexity of this matrix. In the present study, human
      gallbladder bile was obtained from a cholesterol stone patient, and the proteins
      were isolated and purified by dialysis, precipitation and delipidation
      procedures. The resulting proteins were divided into several aliquots. One
      aliquot was subjected to two-dimensional gel electrophoresis (2DE). The protein
      spots were then in-gel digested and analyzed by liquid chromatography coupled
      with tandem mass spectrometry (LC/MS/MS). Another aliquot was directly digested
      and analyzed by a combination of strong cation-exchange (SCX) and reversed-phase
      (RP) chromatography prior to tandem mass spectrometry (2D-LC/MS/MS). Eventually,
      48 and 218 unique proteins were identified from 2DE/MS and 2D-LC/MS/MS,
      respectively, resulting in a total of 222 unique identified proteins. Of the 218
      proteins identified by 2D-LC/MS/MS, 92 were identified based on more than one
      unique tryptic peptide, and, of the total 222 proteins, 98 were identified based
      on more than one unique tryptic peptide.

PMID- 16276487
TI  - Improvement of sample pretreatment prior to analysis of C-peptide in serum by
      isotope-dilution liquid chromatography/tandem mass spectrometry.

PMID- 16276488
TI  - Determination of clenbuterol concentration in human blood using liquid
      chromatography with electrospray/ion-trap tandem mass spectrometry.

PMID- 16276489
TI  - Mechanistic elucidation of the formation of reduced 2-aminopyridine-derivatized
      oligosaccharides and their application in matrix-assisted laser
      desorption/ionization mass spectrometry.

PMID- 16276490
TI  - Absolute oxygen tension (pO(2)) in murine fatty and muscle tissue as determined
      by EPR.
AB  - The absolute partial pressure of oxygen (pO(2)) in the mammary gland pad and
      femoral muscle of female mice was measured using EPR oximetry at 700 MHz. A small
      quantity of lithium phthalocyanine (LiPc) crystals was implanted in both mammary
      and femoral muscle tissue of female C3H mice. Subsequent EPR measurements were
      carried out 1-30 days after implantation with or without control of core body
      temperature. The pO(2) values in the tissue became stable 2 weeks after
      implantation of LiPc crystals. The pO(2) level was found to be higher in the
      femoral muscle than in the mammary tissue. However, the pO(2) values showed a
      strong dependence on the core body temperature of the mice. The pO(2) values were
      responsive to carbogen (95% O(2), 5% CO(2)) breathing even 44-58 days after the
      implantation of LiPc. The LiPc linewidth was also sensitive to changes in the
      blood supply even 60 days after implantation of the crystals. This study further
      validates the use of LiPc crystals and EPR oximetry for long-term non-invasive
      assessment of pO(2) levels in tissues, underscores the importance of maintaining
      normal body core temperature during the measurements, and demonstrates that
      mammary tissue functions at a lower pO(2) level than muscle in female C3H mice.

PMID- 16276491
TI  - Monitoring T-lymphocyte trafficking in tumors undergoing immune rejection.
AB  - Activated T cells, isolated from animals that had rejected a tumor (E.G7-OVA)
      expressing chicken ovalbumin, were labeled with citrated superparamagnetic iron
      oxide nanoparticles at an intracellular iron concentration of up to 0.5 pg/cell.
      Injection of these labeled T cells into animals bearing E.G7-OVA tumors
      undergoing immune rejection resulted in tumor infiltration of these cells, which
      was detectable as a heterogeneous decrease in intensity in T(2)-weighted MR
      images. T-cell infiltration was confirmed by immunohistochemical staining of
      tumor sections obtained postmortem and was shown to colocalize with iron that had
      been stained using Prussian blue. Tumor rejection was correlated with the uptake
      of labeled T cells, since the infiltration of labeled T cells was only observed
      in those tumors that went on to regress. This technique should assist in the
      elucidation of those factors that are important in mediating tumor immune
      rejection.

PMID- 16276492
TI  - Accelerating cine phase-contrast flow measurements using k-t BLAST and k-t SENSE.
AB  - Conventional phase-contrast velocity mapping in the ascending aorta was combined
      with k-t BLAST and k-t SENSE. Up to 5.3-fold net acceleration was achieved,
      enabling single breath-hold acquisitions. A standard phase-contrast (PC) sequence
      with interleaved acquisition of the velocity-encoded segments was modified to
      collect data in 2 stages, a high-resolution under sampled and a low-resolution
      fully sampled training stage. In addition, a modification of the k-t
      reconstruction strategy was tested. This strategy, denoted as "plug-in,"
      incorporates data acquired in the training stage into the final reconstruction
      for improved data consistency, similar to conventional keyhole. "k-t SENSE plug
      in" was found to provide best image quality and most accurate flow
      quantification. For this strategy, at least 10 training profiles are required to
      yield accurate stroke volumes (relative deviation <5%) and good image quality. In
      vivo 2D cine velocity mapping was performed in 6 healthy volunteers with 30-32
      cardiac phases (spatial resolution 1.3 x 1.3 x 8-10 mm(3), temporal resolution of
      18-38 ms), yielding relative stroke volumes of 106 +/- 18% (mean +/- 2*SD) and
      112 +/- 15% for 3.8 x and 5.3 x net accelerations, respectively. In summary, k-t
      BLAST and k-t SENSE are promising approaches that permit significant scan-time
      reduction in PC velocity mapping, thus making high-resolution breath-held flow
      quantification possible.

PMID- 16276493
TI  - Complex genital system of a haplogyne spider (Arachnida, Araneae, Tetrablemmidae)
      indicates internal fertilization and full female control over transferred sperm.
AB  - The female genital organs of the tetrablemmid Indicoblemma lannaianum are
      astonishingly complex. The copulatory orifice lies anterior to the opening of the
      uterus externus and leads into a narrow insertion duct that ends in a genital
      cavity. The genital cavity continues laterally in paired tube-like copulatory
      ducts, which lead into paired, large, sac-like receptacula. Each receptaculum has
      a sclerotized pore plate with associated gland cells. Paired small fertilization
      ducts originate in the receptacula and take their curved course inside the
      copulatory ducts. The fertilization ducts end in slit-like openings in the
      sclerotized posterior walls of the copulatory ducts. Huge masses of secretions
      forming large balls are detectable in the female receptacula. An important
      function of these secretory balls seems to be the encapsulation of spermatozoa in
      discrete packages in order to avoid the mixing of sperm from different males. In
      this way, sperm competition may be completely prevented or at least severely
      limited. Females seem to have full control over transferred sperm and be able to
      express preference for spermatozoa of certain males. The lumen of the sperm
      containing secretory balls is connected with the fertilization duct. Activated
      spermatozoa are only found in the uterus internus of females, which is an
      indication of internal fertilization. The sperm cells in the uterus internus are
      characterized by an extensive cytoplasm and an elongated, cone-shaped nucleus.
      The male genital system of I. lannaianum consists of thick testes and thin
      convoluted vasa deferentia that open into the wide ductus ejaculatorius. The
      voluminous globular palpal bulb is filled with seminal fluid consisting of a
      globular secretion in which only a few spermatozoa are embedded. The spermatozoa
      are encapsulated by a sheath produced in the genital system. The secretions in
      females may at least partly consist of male secretions that could be involved in
      the building of the secretory balls or play a role in sperm activation. The male
      secretions could also afford nutriments to the spermatozoa.

PMID- 16276494
TI  - Use of electrospray ionization mass spectrometry for profiling of crude oil
      effects on the phospholipid molecular species of two marine bacteria.
AB  - We investigated the membrane lipid composition of two hydrocarbon-degrading gram
      negative bacterial strains (Pseudomonas nautica IP 617 and Marinobacter
      hydrocarbonoclasticus) initially cultured on a soluble substrate, then on
      petroleum hydrocarbons, and finally taken back onto the soluble substrate. For
      the two strains, the growth on petroleum and the return to the initial medium
      showed major, but comparable, qualitative and quantitative modifications of the
      intact phospholipid molecular species (IPMS) composition. Furthermore, since
      bacterial membranes are mainly made up of phospholipids, these modifications
      reflected hydrocarbon assimilation, restoration abilities and membrane fluidity
      adaptation. The electrospray ionization mass spectrometry (ESI-MS) analysis of
      intact phospholipid provided some new information (e.g. sn fatty acyl chain
      distribution) that could not be assessed by the classical fatty acid analysis.
      Moreover, such information should be particularly helpful with regards to
      bacterial taxonomy and xenobiotic toxicity studies.

PMID- 16276495
TI  - Characterization of intact Penicillium spores by matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - The fungal spores of Penicillium expansum, P. chrysogenum, P. citrinum, P.
      digitatum, P. italicum, and P. pinophilum were characterized by using matrix
      assisted laser desorption/ionization with time-of-flight mass spectrometry (MALDI
      TOFMS). These fungal spores are frequently found in grain and fruit. The mass
      spectra of these six species were directly obtained from the intact spores
      without any pretreatment. The results obtained indicate that 2,5-dihydroxybenzoic
      acid and sinapinic acid are suitable matrices for the analysis of Penicillium
      spores. Characteristic ions representing the different species were obtained with
      sufficiently high reproducibility that these ions can be employed to identify the
      different fungal species. On the basis of these characteristic ions obtained from
      these authentic Penicillium spores, the approach was applied to characterize the
      fungal species contaminating the surfaces of fruit. It was demonstrated that the
      fungal spores directly scratched from the surfaces of fruit contaminated by
      unknown fungi can be rapidly identified using MALDI-TOFMS analysis without any
      tedious pretreatment.

PMID- 16276496
TI  - Synthesis and characterization of ethyl sulfate and D5-ethyl sulfate as reference
      substances for applications in clinical and forensic toxicology.

PMID- 16276497
TI  - Simultaneous phase correction and SENSE reconstruction for navigated multi-shot
      DWI with non-cartesian k-space sampling.
AB  - Phase-navigated multi-shot acquisition and parallel imaging are two techniques
      that have been applied to diffusion-weighted imaging (DWI) to diminish
      distortions and to enhance spatial resolution. Specifically, sensitivity encoding
      (SENSE) has been combined with single-shot echo planar imaging (EPI). Thus far,
      it has been difficult to apply parallel imaging methods, like SENSE, to multi
      shot DWI because motion-induced phase error varies from shot to shot and
      interferes with sensitivity encoding. Although direct phase subtraction methods
      have been introduced to correct this phase error, they generally are not suitable
      for SENSE reconstruction, and they cannot remove all the motion artifacts even if
      the phase error is fully known. Here, an effective algorithm is proposed to
      correct the motion-induced phase error using an iterative reconstruction. In this
      proposed conjugate-gradient (CG) algorithm, the phase error is treated as an
      image encoding function. Given the complex perturbation terms, diffusion-weighted
      images can be reconstructed using an augmented sensitivity map. The mathematical
      formulation and image reconstruction procedures of this algorithm are similar to
      the SENSE reconstruction. By defining a dynamic composite sensitivity, the CG
      phase correction method can be conveniently incorporated with SENSE
      reconstruction for the application of multi-shot SENSE DWI. Effective phase
      correction and multi-shot SENSE DWI (R = 1 to 3) are demonstrated on both
      simulated and in vivo data acquired with PROPELLER and SNAILS.

PMID- 16276498
TI  - Tissue segmentation and classification of MRSI data using canonical correlation
      analysis.
AB  - In this article an accurate and efficient technique for tissue typing is
      presented. The proposed technique is based on Canonical Correlation Analysis, a
      statistical method able to simultaneously exploit the spectral and spatial
      information characterizing the Magnetic Resonance Spectroscopic Imaging (MRSI)
      data. Recently, Canonical Correlation Analysis has been successfully applied to
      other types of biomedical data, such as functional MRI data. Here, Canonical
      Correlation Analysis is adapted for MRSI data processing in order to retrieve in
      an accurate and efficient way the possible tissue types that characterize the
      organ under investigation. The potential and limitations of the new technique
      have been investigated by using simulated as well as in vivo prostate MRSI data,
      and extensive studies demonstrate a high accuracy, robustness, and efficiency.
      Moreover, the performance of Canonical Correlation Analysis has been compared to
      that of ordinary correlation analysis. The test results show that Canonical
      Correlation Analysis performs best in terms of accuracy and robustness.

PMID- 16276499
TI  - Fluorescent detection of apoptotic cells by using zinc coordination complexes
      with a selective affinity for membrane surfaces enriched with phosphatidylserine.
AB  - The appearance of phosphatidylserine on the membrane surface of apoptotic cells
      (Jurkat, CHO, HeLa) is monitored by using a family of bis(Zn2+-2,2'
      dipicolylamine) coordination compounds with appended fluorescein or biotin groups
      as reporter elements. The phosphatidylserine affinity group is also conjugated
      directly to a CdSe/CdS quantum dot to produce a probe suitable for prolonged
      observation without photobleaching. Apoptosis can be detected under a wide
      variety of conditions, including variations in temperature, incubation time, and
      binding media. Binding of each probe appears to be restricted to the cell
      membrane exterior, because no staining of organelles or internal membranes is
      observed.

PMID- 16276500
TI  - Synthesis and properties of aminopropyl nucleic acids.
AB  - Oligonucleotides that contain up to three aminopropyl nucleoside analogues have
      been synthesized. Dimers of aminopropyl adenine and thymidine were prepared and
      used as building blocks by applying phosphoramidite chemistry. Both R and S
      isomers of the aminopropyl nucleosides were used. This incorporation led to a
      reduction of thermal stability of double-stranded DNA. Furthermore, the (R)
      adenine analogue, which yielded (S)-APNA, can be considered as a candidate for
      universal base pairing.

PMID- 16276501
TI  - Site-specific fluorescent and affinity labelling of RNA by using a small
      engineered twin ribozyme.

PMID- 16276502
TI  - Evidence for the unusual condensation of a diketide with a pentulose in the
      methylenomycin biosynthetic pathway of Streptomyces coelicolor A3(2).

PMID- 16276503
TI  - Acyl transfer in clorobiocin biosynthesis: involvement of several proteins in the
      transfer of the pyrrole-2-carboxyl moiety to the deoxysugar.
AB  - Clorobiocin is an aminocoumarin antibiotic containing a pyrrole-2-carboxyl
      moiety, attached through an ester bond to a deoxysugar. The pyrrole moiety is
      important for the binding of the antibiotic to its biological target, gyrase. The
      complete biosynthetic gene cluster for clorobiocin has been cloned and sequenced
      from the natural producer, Streptomyces roseochromogenes DS 12.976. In this
      study, the genes cloN1 and cloN7 were deleted separately from a cosmid containing
      the complete clorobiocin cluster. The modified cosmids were introduced into the
      genome of the heterologous host Streptomyces coelicolor M512 by using the
      integration functions of the PhiC31 phage. While a heterologous producer strain
      harbouring the intact clorobiocin biosynthetic gene cluster accumulated
      clorobiocin, the cloN1- and cloN7-defective integration mutants accumulated a
      clorobiocin derivative that lacked the pyrrole-2-carboxyl moiety, while also
      producing free pyrrole-2-carboxylic acid. The structures of these metabolites
      were confirmed by NMR and MS analysis. These results showed that CloN1 and CloN7,
      together with the previously investigated CloN2, are involved in the transfer of
      the pyrrole-2-carboxyl moiety to the deoxysugar of clorobiocin. A possible
      mechanism for the role of these three proteins in the acyl-transfer process is
      suggested.

PMID- 16276504
TI  - Use of short duplexes for the analysis of the sequence-dependent cleavage of DNA
      by a chemical nuclease, a manganese porphyrin.
AB  - A manganese porphyrin, manganese(III)-bis(aqua)-meso-tetrakis(4-N
      methylpyridiniumyl)porphyrin, in the presence of KHSO5 is able to perform
      deoxyribose or guanine oxidation depending on its mode of interaction with DNA.
      These two reactions involve an oxygen-atom transfer or an electron transfer,
      respectively. The oxidative reactivity of the manganese-oxo porphyrin was
      compared on short oligonucleotide duplexes of different sequences. The major
      mechanism of DNA damage is due to deoxyribose hydroxylation at a site of strong
      interaction, an (A.T)3 sequence. Guanine oxidation by electron transfer was found
      not to be competitive with this major mechanism. It was found that a single
      intrastrand guanine was three orders of magnitude less reactive than an (A.T)3
      sequence. The reactivity of a 5'-GG sequence was found to be intermediate and was
      estimated to be two orders of magnitude less than that of an (A.T)3 site. Short
      oligonucleotide duplexes, as double-stranded-DNA models, proved to be convenient
      tools for the study of the comparative reactivity of this reagent toward
      different sequences of DNA. However, they showed a particular reactivity at their
      terminal base pairs (the "end effect") that biased their modeling capacity for
      double-helix-DNA models.

PMID- 16276505
TI  - Decacyclene as complexation manifold: synthesis, structure and properties of its
      Fe2 and Fe4 slipped triple-decker complexes.
AB  - Reaction of [(eta(5)-Me4EtC5)Fe(II)Cl(tmeda)] (tmeda = N,N,N'N'
      tetramethylethylenediamine) with a polyanion solution of decacyclene (1) results
      in the formation of the triple-deckers [{(eta(5)-Me4EtC5)Fe}2-mu2-(eta(6):eta(6)
      decacyclene)] (3) and [{(eta(5)-Me4EtC5)Fe}4-mu4-(eta(6):eta(6):eta(6):eta(6)
      decacyclene)] (4). Metal complexation in 3 and 4 occurs on opposite faces of the
      pi perimeter in an alternating mode. The decacyclene ring adopts a gently twisted
      molecular propeller geometry with twofold crystallographic symmetry (C2). Complex
      4 crystallizes in the chiral space group C222(1); the investigated crystal only
      contains decacyclene rings with M chirality. The handedness can be assigned
      unambiguously to the presence of the iron atoms. Cyclovoltammetric studies
      revealed quasireversible behavior of the redox events and a strong interaction of
      the Fe atoms in 3 and 4, exemplified by potential differences deltaE of 660 and
      770(780) mV between the first and the second individual oxidation processes. This
      corresponds to a high degree of metal-metal interaction for 3 and 4. The
      successful syntheses of 3 and 4 together with earlier results from our laboratory
      proves that all five- and six-membered pi subunit sets of 1 are prone to metal
      complexation. A clear site preference in 1 towards the complexation of
      [Cp(R)]iron, -cobalt, and -nickel fragments exists.

PMID- 16276506
TI  - Mouse model for ablation of proliferating microglia in acute CNS injuries.
AB  - Activation of microglia, the primary immune effectors of the CNS and
      proinflammatory signaling, is a hallmark of brain damage. However, it remains
      controversial whether microglial cells have beneficial or detrimental functions
      in various neuropathological conditions. We report the generation of transgenic
      mice that express a mutant form of herpes simplex virus type 1 thymidine kinase
      (HSV-1 TK(mt-30)) driven by the myeloid-specific CD11b promoter. Using two
      paradigms of nervous system damage, hypoglossal nerve axotomy, and cortical stab
      injury, we show that specific ablation of proliferating microglia in CD11b-TK(mt
      30) mice can be achieved by administration of ganciclovir. For example, after
      hypoglossal nerve injury, a 75% reduction in proliferating microglial cells was
      observed at the site of injury. The CD11b-TK(mt-30) transgenic mouse should
      provide a valuable tool for studying the role of microglia in CNS damage and
      repair.

PMID- 16276507
TI  - Quantifying the spatial resolution of the gradient echo and spin echo BOLD
      response at 3 Tesla.
AB  - The blood oxygen level dependent (BOLD) response, as measured with fMRI, offers
      good spatial resolution compared to other non-invasive neuroimaging methods. The
      use of a spin echo technique rather than the conventional gradient echo technique
      may further improve the resolution by refocusing static dephasing effects around
      the larger vessels, so sensitizing the signal to the microvasculature. In this
      work the width of the point spread function (PSF) of the BOLD response at a field
      strength of 3 Tesla is compared for these two approaches. A double echo EPI pulse
      sequence with simultaneous collection of gradient echo and spin echo signal
      allows a direct comparison of the techniques. Rotating multiple-wedge stimuli of
      different spatial frequencies are used to estimate the width of the BOLD
      response. Waves of activation are created on the surface of the visual cortex,
      which begin to overlap as the wedge separation decreases. The modulation of the
      BOLD response decreases with increasing spatial frequency in a manner dependent
      on its width. The spin echo response shows a 13% reduction in the width of the
      PSF, but at a cost of at least 3-fold reduction in contrast to noise ratio.

PMID- 16276508
TI  - Ultrastructure of the maxillary organ of Scutigera coleoptrata (Chilopoda,
      Notostigmophora): description of a multifunctional head organ.
AB  - The maxillary organ of Scutigera coleoptrata was investigated using light
      microscopy, electron microscopy, and maceration techniques. Additionally, we
      compared the maxillary organ of S. coleoptrata with those of two other
      notostigmophoran centipedes, Parascutigera festiva and Allothereua maculata,
      using SEM. The maxillary organ is located inside the posterior coxal lobes of the
      first maxillae and extends posteriorly as sac-like pouches. The narrow epidermis
      of the maxillae is differentiated to form the epithelium of the maxillary organ.
      Two types of epithelia are distinguishable: a simple cuboidal epithelium of
      different height and differentiation (types I, II, IV) and a pseudostratified
      columnar epithelium (type III). These epithelia are covered by a highly
      specialized cuticle. The pseudostratified epithelium is the most prominent
      feature of the maxillary organ. It is covered with hundreds of setae, protruding
      deep into the maxillary organ. Two different types of setae can be distinguished,
      filiform and fusiform. The maxillary organ communicates with the oral cavity, the
      maxillary organ gland, the maxillary nephridium, and with a large number of
      epidermal glands that secrete into the maxillary organ. Epithelium III allows the
      extension of the maxillary organ when its pouches are filled with secretion. The
      maxillary organ is a complex multifunctional organ. The organ probably stores
      excretion from the maxillary nephridia and secretory fluid from the maxillary
      organ gland and other epidermal glands. The fluid is primarily required as
      preening fluid. The ammonia of the excretory fluid is thought to evaporate via
      the setae and the wide opening of the maxillary organ. It is likely that parts of
      the fluid can be reabsorbed by the animal via the oral cavity.

PMID- 16276509
TI  - Alterations of lymphocyte membranes during HIV-1 infection via multiple and
      simultaneous entry strategies.
AB  - Human immunodeficiency virus type 1 (HIV-1) must bind to and enter lymphocytes to
      replicate and cause the acquired immunodeficiency syndrome. The association of
      viral particles with the lymphocyte plasma membrane may vary according to a
      multitude of unknown variables, including lymphocyte membrane receptor
      mobilization, lipid raft aggregation, clathrin, caveolin, endosomes,
      microendosome-mediated penetration or penetration through a hole in the membrane.
      The time course of this delivery appears to be short. Fusion of the virion
      membrane and lymphocyte plasma membrane leads to destabilization of the
      lymphocyte membrane. Five morphological stages of membrane alteration were
      observed in the infected lymphocytes: (1) swelling, (2) splitting, (3) fusion,
      (4) breaking, and (5) thinning of the lipid bilayer. These plasma membrane
      alterations were not contributed by fixation artifacts, because the dimensions
      and distance between the subunits of the surface glycoprotein (SU, gp120) and the
      transmembrane glycoprotein (gp41) of the viral particles adjacent to the infected
      cells and processed at the same time remained unchanged. Destabilization of lipid
      raft patches in the lymphocyte plasma membrane by unknown variables may
      facilitate HIV-1 penetration of lymphocyte, and other cell types. This a combined
      review of the pertinent literature with our data showing that HIV-1 may take
      advantage of multiple penetration approaches simultaneously in the same cell type
      (H9) to overwhelm the infected cells. The ultrastructural details of H9 cultured
      cells infected in vitro with HIV-1 contribute to our understanding of viral
      particle association with the plasma membrane of infected cells.

PMID- 16276510
TI  - Human, rhesus macaque, and feline sequences highly similar to mouse mammary tumor
      virus sequences.
AB  - Sequences highly similar (>95%) to the mouse mammary tumor virus (MMTV) env gene
      have been amplified from human DNA samples, including DNA samples from patients
      with breast cancer (BC) and persons who did not have BC. The sequences from human
      DNA were distinct from the MMTV sequences used as controls in these PCR
      reactions, indicating that these results are not simply due to contamination. In
      addition to both, mouse and human-related sequences were also amplified from some
      monkey and cat genomic DNA samples. These products were shown to be distinct
      from, but highly related to, the MMTV env gene, whereas, testing of other sources
      (lambda phage, snake, cockroach, sea urchin, chicken, or dog) demonstrated no
      specific amplification. A sequence 90% similar to the MMTV group antigen gene
      (gag) was amplified from cat DNA. These results indicate that DNA from vertebrate
      species other than rodents, including some but not all humans, monkeys, and cats,
      can contain sequences closely related to MMTV.

PMID- 16276511
TI  - Seroreactivity to A-type retrovirus proteins in a subset of cats with
      hyperthyroidism.
AB  - The thyroid gland is afflicted in several endocrine, autoimmune, and malignant
      diseases. Previous studies detected immunoreactivity against proteins of a human
      intracisternal A-type retroviral particle type-I (HIAP-I) in serum samples from
      the majority of patients with Graves' disease, an autoimmune disease of the
      thyroid that can also affect other organs, most prominently the eyes. To
      determine whether hyperthyroid animals might provide a model for the retroviral
      involvement in thyroid autoimmunity, serum samples from 32 cats (21 hyperthyroid
      and 11 controls) and 10 hypothyroid dogs were examined for immunoreactivity with
      HIAP-I using a Western blot technique. Of the 21 hyperthyroid cats 15 (71.4%)
      were HIAP-I positive, while only 2 of 11 (11.8%) control animals without
      endocrine pathology were positive. No significant correlations were seen between
      HIAP seroreactivity and serum thyroid hormone levels (T3 and T4), age, gender,
      treatment history, vaccination status, or weight. No seroreactivity to HIAP-I was
      detected in hypothyroid dogs. An examination of HIAP-I reactivity in feline
      leukemia virus (FeLV)-seroconverting cats found that 7/9 (78%) animals viremic
      for FeLV-A showed an alteration in HIAP serology, whereas only 1/7 (14%)
      nonviremic animals showed a change in HIAP-I serology. These results suggest that
      it may be possible to develop an animal (feline) model for the role of
      retroviruses in thyroid autoimmune diseases.

PMID- 16276512
TI  - Coexpression of major histocompatibility complex class I and LMP1 in Epstein-Barr
      virus-positive Hodgkin's lymphoma in a pediatric age group.
AB  - The Epstein-Barr virus (EBV)-encoded latent membrane proteins (LMP1 and LMP2) are
      consistently expressed by malignant Hodgkin Reed-Sternberg (HRS) cells of EBV
      associated Hodgkin's disease (HD). The EBV LMP1 has been implicated in
      tumorogenesis. Cytotoxic T lymphocyte (CTL) responses to both of these proteins
      have been shown in the blood of EBV-seropositive individuals, and in HD, the
      apparent failure of the CTL response to eliminate HRS cells expressing LMP1 in
      vivo has given rise to the suggestion that HD may be characterized by the
      presence of defects in antigen CTL-presentation or in CTL dysfunction. This study
      examined 28 cases seen at the Regional Children's Hospital Arturo Grullon in
      Santiago, the Dominican Republic, by immunohistochemistry. High level of
      expression of major histocompatibility complex (MHC) class I molecules in HRS
      cells of EBV-associated HD was recorded. These results suggest that deregulation
      of MHC class I molecules does not account for the apparent ability of EBV to
      infect HRS cells and to evade CTL protection. Therefore, the result from our work
      and similar studies will help to determine whether, or which, immunotherapy
      should be used in positive and negative cases of HD related to EBV.

PMID- 16276514
TI  - HCV-hepatocellular carcinoma: new findings and hope for effective treatment.
AB  - We present here a comprehensive review of the current literature plus our own
      findings about in vivo and in vitro analysis of hepatitis C virus (HCV)
      infection, viral pathogenesis, mechanisms of interferon action, interferon
      resistance, and development of new therapeutics. Chronic HCV infection is a major
      risk factor for the development of human hepatocellular carcinoma. Standard
      therapy for chronic HCV infection is the combination of interferon alpha and
      ribavirin. A significant number of chronic HCV patients who cannot get rid of the
      virus infection by interferon therapy experience long-term inflammation of the
      liver and scarring of liver tissue. Patients who develop cirrhosis usually have
      increased risk of developing liver cancer. The molecular details of why some
      patients do not respond to standard interferon therapy are not known.
      Availability of HCV cell culture model has increased our understanding on the
      antiviral action of interferon alpha and mechanisms of interferon resistance.
      Interferons alpha, beta, and gamma each inhibit replication of HCV, and the
      antiviral action of interferon is targeted to the highly conserved 5'UTR used by
      the virus to translate protein by internal ribosome entry site mechanism. Studies
      from different laboratories including ours suggest that HCV replication in
      selected clones of cells can escape interferon action. Both viral and host
      factors appear to be involved in the mechanisms of interferon resistance against
      HCV. Since interferon therapy is not effective in all chronic hepatitis C
      patients, alternative therapeutic strategies are needed to treat chronic
      hepatitis C patients not responding to interferon therapy. We also reviewed the
      recent development of new alternative therapeutic strategies for chronic
      hepatitis C, which may be available in clinical use within the next decade. There
      is hope that these new agents along with interferon will prevent the occurrence
      of hepatocellular carcinoma due to chronic persistent hepatitis C virus
      infection. This review is not inclusive of all important scientific publications
      due to space limitation.

PMID- 16276515
TI  - AIDS-related non-Hodgkin's lymphomas.
AB  - This work reviews the current status of non-Hodgkin's lymphoma (NHL) in HIV
      infected patients. HIV infection remains at significantly increased risk for the
      development of NHL. The great majority of these lymphomas are high-grade
      monoclonal B-cell neoplasms often occurring in unusual sites. A number of genetic
      abnormalities have been found but additional studies are necessary to understand
      the etiology and pathogenesis of NHL in the setting of HIV infection. The cases
      in this paper have been seen on the Hematopathology service of the Tulane Health
      Sciences Center.

PMID- 16276516
TI  - Of mice, cats, and men: is human breast cancer a zoonosis?
AB  - Mouse mammary tumor virus (MMTV), a member of the betaretroviridae, is the most
      common cause of breast cancer (BC) in mice. MMTV is transmitted in mice both in
      the germline as endogenous proviruses and exogenously as infectious virions.
      Here, we review a variety of evidence accumulated for six decades that has
      suggested that a human homologue of MMTV may exist. The findings include recent
      studies from several independent laboratories that have detected sequences very
      closely related to MMTV in DNA isolated from human BC tumors. Other laboratories,
      however, have failed to detect the MMTV-related sequences in human DNA samples,
      and conclusive evidence for a human mammary tumor virus has been elusive. We also
      reviewed additional studies, suggesting that betaretroviruses are present in a
      much wider range of species than previously known, including rodents, felines,
      and primates. The observation that a subset of cats may be infected with a close
      homologue of MMTV may be of epidemiological significance for human BC. Cats may
      become infected by MMTV from mice, and in turn may transmit the virus to humans,
      possibly after selection for variants with an expanded host range.

PMID- 16276517
TI  - Involvement of human intracisternal A-type retroviral particles in autoimmunity.
AB  - Prior studies have linked retroviruses to various arthropathies and autoimmune
      diseases. Sjogren's syndrome (SS), a systemic autoimmune disease, is
      characterized by aggressive infiltration of lymphocytes into the salivary and
      lacrimal glands, resulting in destruction of the glands and dry mouth and eyes
      (sicca syndrome). The infiltrating lymphocytes in SS may become overtly
      malignant, and thus, the incidence of lymphoma is greatly increased in SS
      patients. A human intracisternal A-type retroviral particle type I (HIAP-I) has
      been isolated from persons with SS. HIAP-I shares a limited number of antigenic
      epitopes with human immunodeficiency virus (HIV), but is distinguishable from HIV
      by morphological, physical, and biochemical criteria. A substantial majority of
      patients with SS or systemic lupus erythematosus (SLE) have serum antibodies to
      the proteins of this human retrovirus. Fewer than 3% of the normal blood donor
      population have antibodies to any HIAP-associated proteins. A second type of a
      human intracisternal A-type retrovirus, HIAP-II, was detected in a subset of
      patients with idiopathic CD4 lymphocytopenia (ICL), an AIDS-like immunodeficiency
      disease. Most HIAP-II positive ICL patients were also antinuclear antibody
      positive. Reviewed here are additional studies from several laboratories
      suggesting that HIAP or related viruses may be involved in SLE and other
      autoimmune conditions. Additionally, results of comprehensive surveys of
      autoimmune patients to determine seroreactivity to HIAP, and other human
      retroviruses, including HIV and human T-lymphotropic virus type I, are reported.

PMID- 16276518
TI  - Slow virus disease: deciphering conflicting data on the transmissible spongiform
      encephalopathies (TSE) also called prion diseases.
AB  - The transmissible spongiform encephalopathies (TSE) that manifest as Creutzfeldt
      Jakob disease in humans, as scrapie in sheep and goats, mad cow disease in
      cattle, or chronic wasting disease in cervids (deer) represent a serious human
      health crisis and a significant economical problem. Despite much research, the
      nature of the elusive pathogen directly involved with TSE is currently
      unresolved. This article reviews current pathogen-cell plasma membrane
      properties, showing that the primary biochemical marker of the prion disease is
      used as a receptor by the intracellular bacterium Brucella abortus. Such
      observation makes plausible the role for the prion in the pathogenesis of TSE,
      and supports the concept that Spiroplasma, a wall-less bacterium, may be a
      transmissible agent of TSE. Over the past three decades, we have published
      convincing evidence that Spiroplasma infection is associated with TSE. The
      bacterial-prion-receptor concept by other laboratories support a model for TSE
      wherein a Spiroplasma bacterium can bind to prion receptors (alone or with
      anchors) on the cell surface lipid raft, allowing entry of the microbe into the
      cell to initiate infection. The relevance of this new concept is that it offers a
      new window for future research involving a bacterium in the pathogenesis of TSE.
      Data from the bacterial-prion-receptor model will aid in the development
      diagnostic tests and/or treatment protocols for TSE.

PMID- 16276519
TI  - Gamma-herpesvirus neoplasia: a growing role for COX-2.
AB  - Both human gamma-herpesviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma
      associated herpesvirus (KSHV) induce neoplasia. Burkitt's and Hodgkin's lymphomas
      harbor EBV sequences, while KSHV has been associated with Kaposi's sarcoma (KS),
      primary effusion lymphoma (PEL), and multicentric castleman's disease (MCD). Each
      of these gamma-herpesvirus-associated malignancies displays typical
      characteristics of neoplasia, such as angiogenesis and cell survival. One enzyme
      commonly overexpressed in breast, prostate, and colon cancers is cyclooxygenase-2
      (COX-2). Recently, COX-2 overexpression has been reported in herpesvirus
      infections in vitro. This review will outline potential mechanisms by which COX-2
      may participate in herpesvirus-induced neoplasia.

PMID- 16276520
TI  - Dengue in the Dominican Republic: epidemiology for 2004.
AB  - The Dominican Republic (DR) has experienced tremendous increase in the number of
      cases of dengue virus (DENV) reported in the past few years. There are four
      serotypes of DENV (1-4), and each can cause classic dengue fever (DF), dengue
      hemorrhagic fever (DHF), or dengue shock syndrome (DSS). DENV-1-4 are currently
      circulating in the DR; however, the Department of Epidemiology of the Dominican
      Republic (DIEGPI) has been able to isolate only DENV-2 and DENV-4. In the DR, the
      development of DENV infection occurred primarily in the second semester of the
      year. Since the DR instituted a vigilant approach to dengue infections, there
      have been three major outbreaks detected: one in 1998, one in 2000, and one in
      2002. DF is the clinical presentation most currently seen at clinics, accounting
      for about 75% of cases, while patients with DHF account for about 19% of cases
      seen. Currently, there are seven provinces in which the total number of dengue
      cases per 100,000 inhabitants is higher than 32. With a vigilant approach, the DR
      should continue to see success in controlling the DENV outbreak.

PMID- 16276521
TI  - The glycine 90 to aspartate alteration in the Abeta subunit of PP2A (PPP2R1B)
      associates with breast cancer and causes a deficit in protein function.
AB  - Mutations of the PPP2R1B gene, which encodes the Abeta scaffolding subunit of
      serine/threonine protein phosphatase 2A (PP2A), have been identified in several
      types of cancer including lung and breast carcinoma. One of these mutations
      results in an alteration of glycine 90 to aspartic acid (G90D), which has been
      found in both tumor and genomic DNA, raising the possibility that it is
      associated with an increased risk for cancer. A novel microarray-based technology
      was used to screen for this single-nucleotide polymorphism in 387 cancer patients
      and 329 control individuals. These data were used for case-control and family
      based comparisons in order to study the association of this polymorphism with
      susceptibility to lung carcinoma, breast carcinoma, and acute lymphoblastic
      leukemia. The frequency of the G90D polymorphism in breast cancer patients was
      significantly higher in cases (3%) than in controls (0.3%). The wild-type Abeta
      subunit interacted with the B56gamma (PPP2R5C), PR72 (PPP2R3A), and PR48 subunits
      of PP2A but did not interact with the B55alpha (PPP2R2A), B56alpha (PPP2R5A), or
      B56beta (PPP2R5B) regulatory subunits in an in vitro binding assay. The G90D
      alteration inhibited the interaction of Abeta with the B56gamma subunit but had
      no effect on binding to the PR72 subunit. These results provide evidence that the
      G90D alteration of the Abeta subunit of PP2A is associated with a low frequency
      of breast carcinoma and that the role of this alteration in transformation is
      likely to involve decreased interaction with the B56gamma regulatory subunit.

PMID- 16276522
TI  - Pulmonary Langerhans cell histiocytosis: a variable disease in childhood.
AB  - BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is rare in childhood
      but occurs most commonly in children with multisystem (MS) LCH. In adults, by
      contrast, the lung is the most common and usually the sole organ affected. This
      retrospective study describes the clinical manifestation, course, and outcome of
      PLCH in children consecutively diagnosed at two Canadian institutions. PROCEDURE:
      The medical records of children (<18 years of age) consecutively diagnosed with
      LCH at the two institutions, were examined to ascertain the demographic details,
      pathological diagnosis, and organs involved. Further clinical details including,
      the clinical manifestation, details of therapy, course of lung disease, and
      clinical outcome were extracted for patients with PLCH. Initial and follow-up
      lung radiographs and CT scans were re-reviewed. RESULTS: Of the 178 patients with
      LCH, 40 (22.5%) presented with MS disease. Thirteen (7.3%) had PLCH, seven at
      initial diagnosis, and six at the time of disease progression. The median age was
      10.1 months and mean was 11.9 months at diagnosis of PLCH. Lung involvement was
      always in the context of MS LCH, and half of the patients had no respiratory
      symptoms. Disease-free survival was around 70%, with a mean follow-up duration of
      7 years. Of the four patients who died, three had other risk-organ involvement.
      Five of the nine surviving patients have had complete radiological resolution of
      PLCH. CONCLUSION: PLCH is seen in less than 10% of childhood LCH, but more than
      30% of MS LCH. About half of children with PLCH may be asymptomatic, and the
      prognosis appears to depend on the presence or absence of other risk-organ
      involvement. The MS PLCH found in children appears to be a different disease from
      the single system (SS) PLCH seen in adults.

PMID- 16276523
TI  - Does intravenous 6-mercaptopurine decrease salvage after relapse in childhood
      acute lymphoblastic leukemia?

PMID- 16276524
TI  - Academic training pathways in pediatric hematology-oncology.

PMID- 16276525
TI  - Is an ounce of prevention worth a pound of cure?

PMID- 16276526
TI  - Analysis of needle versus open biopsy for the diagnosis of advanced stage
      pediatric neuroblastoma.
AB  - BACKGROUND: Adequate tissue biopsy is necessary for the appropriate diagnosis and
      risk stratification of pediatric neuroblastoma (NB). We compared the quality and
      adequacy of biopsy tissue and complication rates in children with NB who
      underwent open (OBX) and image-guided needle biopsy (NBX) at our center. METHODS:
      We retrospectively reviewed all patients diagnosed with stage III and IV NB from
      September 2001 to August 2004. The 24 patients were divided into two groups:
      those in whom the diagnosis was initiated using NBX, and those diagnosed using
      OBX. In addition to demographic data, we collected data pertaining to sufficiency
      of biopsy tissue for biology studies including: Shimada Classification, MYC-N
      amplification, and DNA index analysis and complications associated with the
      procedure. Chi-Square and Student's t-test were used to analyze the categorical
      and continuous variables, respectively. RESULTS: Of 24 patients, 11 underwent
      NBX, and 13 patients underwent OBX. Eighteen patients had stage IV disease, 5
      patients had stage III disease, and 1 stage IVS. Ten major complications occurred
      in four NBX patients and six OBX patients. There was no difference in days of
      narcotic use, time to DAT, or hospital stay between the two groups. Ten patients
      (seven NBX and three OBX, P = 0.045) had tissue that was insufficient for biology
      studies. Three of the seven NBX patients underwent a second biopsy for
      clarification of risk group. CONCLUSIONS: This study demonstrated that more than
      half of patients undergoing NBX for NB had insufficient tissue for complete
      histological and molecular classification and that the incidence of procedural
      complications between NBX and OBX are similar.

PMID- 16276527
TI  - Acute myeloid leukemia in a child with hereditary thrombocytopenia.
AB  - A child with a known diagnosis of an autosomal dominant macrothrombocytopenia,
      Fechtner Syndrome, developed acute myeloid leukemia (AML). Recently the disease
      gene for the inherited macrothrombocytopenias has been identified as MYH9,
      encoding for non-muscle myosin heavy chain-A. MYH9 has never been associated with
      the development of acute leukemia, but MYH11 is disrupted in the M4 eosinophilia
      sub-type of AML (inv16). The patients leukemic blasts did carry the common
      t(8;21) which yields an AML1-ETO fusion protein that inhibits AML-1. Despite his
      thrombocytopenia, the patient successfully completed intensive bone marrow
      cytoreduction without significant bleeding complications and is now in remission
      for over 3 years.

PMID- 16276529
TI  - Presence of a novel inhibitor of capping protein in neutrophil extract.
AB  - Capping of actin filament barbed ends regulates the duration of filament
      elongation and the steady-state level of actin polymerization. We find that the
      specific capping activity (capping activity per milligram protein) increased when
      a high speed supernatant of lysed neutrophils was diluted with buffer. The
      specific capping activity also increased when the concentration of barbed ends
      increased. This suggested the presence of a capping protein inhibitor that
      dissociates from capping protein upon dilution and that competes with barbed ends
      for binding to capping protein. Gel filtration of supernatant revealed a fraction
      of low-molecular-weight inhibitor (separated from capping protein) that both
      inhibited and reversed capping of barbed ends by pure capping protein. The
      properties and molecular weight of this inhibitor do not match with those of
      other inhibitors including V-1, VASP, or CARMIL. Thus, this inhibitor must either
      be a modified version of a known inhibitor or a novel inhibitor of capping.

PMID- 16276528
TI  - Target selection and deselection at the Berkeley Structural Genomics Center.
AB  - At the Berkeley Structural Genomics Center (BSGC), our goal is to obtain a near
      complete structural complement of proteins in the minimal organisms Mycoplasma
      genitalium and M. pneumoniae, two closely related pathogens. Current targets for
      structure determination have been selected in six major stages, starting with
      those predicted to be most tractable to high throughput study and likely to yield
      new structural information. We report on the process used to select these
      proteins, as well as our target deselection procedure. Target deselection reduces
      experimental effort by eliminating targets similar to those recently solved by
      the structural biology community or other centers. We measure the impact of the
      69 structures solved at the BSGC as of July 2004 on structure prediction coverage
      of the M. pneumoniae and M. genitalium proteomes. The number of Mycoplasma
      proteins for which the fold could first be reliably assigned based on structures
      solved at the BSGC (24 M. pneumoniae and 21 M. genitalium) is approximately 25%
      of the total resulting from work at all structural genomics centers and the
      worldwide structural biology community (94 M. pneumoniae and 86 M. genitalium)
      during the same period. As the number of structures contributed by the BSGC
      during that period is less than 1% of the total worldwide output, the benefits of
      a focused target selection strategy are apparent. If the structures of all
      current targets were solved, the percentage of M. pneumoniae proteins for which
      folds could be reliably assigned would increase from approximately 57% (391 of
      687) at present to around 80% (550 of 687), and the percentage of the proteome
      that could be accurately modeled would increase from around 37% (254 of 687) to
      about 64% (438 of 687). In M. genitalium, the percentage of the proteome that
      could be structurally annotated based on structures of our remaining targets
      would rise from 72% (348 of 486) to around 76% (371 of 486), with the percentage
      of accurately modeled proteins would rise from 50% (243 of 486) to 58% (283 of
      486). Sequences and data on experimental progress on our targets are available in
      the public databases TargetDB and PEPCdb.

PMID- 16276530
TI  - New reaction system for hydrocarbon oxidation by chloroperoxidase.
AB  - A novel reaction system was developed to maximize the catalytic efficiency of
      chloroperoxidase (CPO, from Caldariomyces fumago) toward the oxidation of
      hydrocarbons. The reaction system consisted of an organic/aqueous emulsion
      comprising pure substrate and aqueous buffer supplemented with the surfactant
      dioctyl sulfosuccinate. The emulsion system attenuated not only the destabilizing
      effects of the substrate and product on the enzyme by emulsifying the compounds,
      but also oxidant toxicity (oxidative stress) by increasing substrate
      availability. As a result, CPO exhibited total turnover numbers (TTNs, defined as
      the amount of product produced over the catalytic lifetime of the enzyme) of ca.
      20,000 mol product/mol enzyme for the oxidation of styrene, toluene, and o-, m-,
      p-xylenes. The TTNs are over 10-fold higher than those previously reported for
      the oxidation of benzylic hydrocarbons by CPO. This study represents a
      significant step toward the development of CPO as a practical catalyst for large
      scale organic syntheses.

PMID- 16276531
TI  - Investigation of protein retention and selectivity in HIC systems using
      quantitative structure retention relationship models.
AB  - In the present work, the effect of stationary phase resin chemistry and protein
      physicochemical properties on protein binding affinity in hydrophobic interaction
      chromatography (HIC) was investigated using linear gradient chromatography and
      quantitative structure-retention relationship (QSRR) modeling. Linear gradient
      experiments were carried out for a set of model proteins on four different HIC
      resins having different backbone and ligand chemistry. The retention data
      exhibited significant differences in protein binding affinity, not only across
      the phenyl and butyl ligand chemistries, but also for the different backbone
      chemistries found in the Sepharose (cross-linked agarose) and the Toyopearl 650 M
      (polymethacrylate) series of resins. QSRR models based on a Support Vector
      Machine (SVM) approach were developed for the linear retention data using
      molecular descriptors based on protein crystal structure and primary sequence
      information as well as a set of new hydrophobicity descriptors based on the
      solvent accessible protein surface area. The results indicate that the QSRR
      models were successfully able to capture and selectivity predict the changes
      observed in these systems. Furthermore, the new descriptors resulted in
      physically interpretable models of protein retention and provided insights into
      the factors influencing protein affinity in these different HIC systems. The
      approach put forth in this study provides a framework for developing predictive
      tools and for gaining insight into protein selectivity in hydrophobic interaction
      chromatography.

PMID- 16276532
TI  - Preparative synthesis of dTDP-L-rhamnose through combined enzymatic pathways.
AB  - dTDP-L-rhamnose, an important precursor of O-antigen, was prepared on a large
      scale from dTMP by executing an one-pot reaction in which six enzymes are
      involved. Two enzymes, dTDP-4-keto-6-deoxy-D-glucose 3,5-epimerase and dTDP-4
      keto-rhamnose reductase, responsible for the conversion of dTDP-4-keto-6-deoxy-D
      glucose to dTDP-L-rhamnose, were isolated from their putative sequences in the
      genome of Mesorhizobium loti, functionally expressed in Escherichia coli, and
      their enzymatic activities were identified. The two enzymes were combined with an
      enzymatic process for dTDP-4-keto-6-deoxy-D-glucose involving TMP kinase, acetate
      kinase, dTDP-glucose synthase, and dTDP-glucose 4,6-dehydratase, which allowed us
      to achieve a preparative scale synthesis of dTDP-L-rhamnose using dTMP and
      glucose-1-phosphate as starting materials. About 82% yield of dTDP-L-rhamnose was
      obtained based on initial dTMP concentration at 20 mM dTMP, 1 mM ATP, 10 mM NADH,
      60 mM acetyl phosphate, and 80 mM glucose-1-phosphate. From the reaction with 20
      ml volume, approximately 180 mg of dTDP-L-rhamnose was obtained in an overall
      yield of 60% after two-step purification, that is, anion exchange chromatography
      and gel filtration for desalting. The purified product was identified by HPLC,
      ESI-MS, and NMR, showing about 95% purity.

PMID- 16276533
TI  - Hepatitis B and liver cancer beliefs among Korean immigrants in Western
      Washington.
AB  - Hepatocellular cancer occurs more frequently among Koreans, Vietnamese, and
      Chinese than other racial/ethnic groups in the U.S. This excess risk can be
      attributed to high rates of chronic hepatitis B viral (HBV) infection and low
      rates of HBV vaccination among Asian immigrants. However, there is little
      available information regarding the hepatitis B knowledge, beliefs, and practices
      among Koreans, the fifth-largest Asian population in the U.S. This brief report
      summarizes results from 30 qualitative interviews and two focus groups
      investigating hepatitis and liver cancer prevention, behavior, and beliefs among
      first-generation Korean immigrant adults ages 18-64 years residing in the Seattle
      Tacoma metropolitan area of Washington State. The report concludes with
      suggestions for future investigations to address the high rates of chronic HBV
      infection and hepatocellular cancer in this vulnerable population.

PMID- 16276534
TI  - The Asian-American and Pacific Islander population and the American Cancer
      Society initiative.
AB  - The American Cancer Society (ACS) Nationwide Asian-American/Pacific Islander
      (AAPI) Initiative is a continuing collaboration between the ACS and other
      organizations and community groups. With a view to incorporating access to
      quality treatment as an over-arching principal, the objectives of the AAPI
      Initiative are to provide strategic oversight to the ACS for outreach to AAPI
      populations and to develop a nationwide plan for the purpose of making ACS
      programs and services available to these populations. After a series of meetings
      in 2002, including a joint meeting between the Asian American Network for Cancer
      Awareness, Research, and Training (AANCART) and the ACS, the first ACS Nationwide
      AAPI Council meeting was held in early 2003. The goals and objectives of this
      initiative are 1) to develop a plan for delivery of ACS programs and services to
      the AAPI population, 2) to develop a program for collaboration with organizations
      that can help the ACS reach its objectives, 3) to develop an advocacy program
      that enables the ACS to reach its objectives, and 4) to develop an income
      development program to both reach and maintain these objectives. The ACS-AANCART
      collaboration is a great example of the type of collaboration that will make not
      only the ACS but also the cancer community as a whole successful in eradicating
      cancer as a major public health problem.

PMID- 16276536
TI  - Stimulating cancer research in Asian communities and training the next generation
      of scientists.
AB  - The landmark Institute of Medicine Report on the "Unequal Burden of Cancer"
      urgently called for efforts to reduce cancer disparities by conducting research
      that could rapidly translate laboratory and clinical findings to benefit large
      segments of society. It also called for intensifying efforts to produce well
      trained minority researchers as a way to increase the quantity, quality and
      community relevance of cancer control research. This manuscript summarized our
      strategies and successes in these two areas. Over a five year period, the Los
      Angeles site of the NCI-funded Asian American Network for Cancer Awareness,
      Research, and Training (AANCART-LA) conducted intensive community based cancer
      awareness activities through a coalition of over 20 Asian serving community
      organizations. In addition, a major focus of AANCART-LA was on increasing
      community-relevant research and on training scientists to conduct research among
      Asians. Strategies to reach these goals included a focus on pilot studies as a
      way of introducing the community to research, selection of promising junior
      scientists to submit applications for pilot funding, and close mentoring of these
      individuals by seasoned investigators. We describe four pilot project proposals
      that were selected for funding by the NCI peer review process. In addition,
      AANCART-LA was able to obtain peer reviewed funding for several other research
      projects targeting a variety of Asian sub-groups. These projects were the direct
      outcome of extensive cancer awareness activities in the community, the publicity
      associated with receiving peer-reviewed pilot project funding, and the
      collaborations established with multiple community based organizations.

PMID- 16276535
TI  - Seizing the moment: California's opportunity to prevent nutrition-related health
      disparities in low-income Asian American population.
AB  - Asian Americans and Pacific Islanders (AAPI) have the fastest growing rate of
      overweight and obese children. Aggressive programs are urgently needed to prevent
      unhealthy acculturation-related changes in diet and physical activity and to
      promote the healthier aspects of traditional lifestyle habits. We conducted focus
      groups and key informant interviews to explore knowledge, attitudes, dietary
      practices, and physical activity levels among three low-income Asian American
      ethnic groups, Chinese, Vietnamese, and Hmong, in California. Content analysis
      was used to identify similarities and differences among the groups. Several
      common health beliefs clearly emerged. Participants noted the importance of fresh
      (not frozen) fruit and vegetable consumption and physical activity for general
      health. The concept of good health included having a harmonious family, balance,
      and mental and emotional stability. All groups also expressed the general belief
      that specific foods have hot or cold properties and are part of the Yin/Yang
      belief system common to Asian cultures. The lure of fast food, children's
      adoption of American eating habits, and long work hours were identified as
      barriers to a healthy, more traditional lifestyle. A California campaign for
      Asian Americans using multilevel strategies is recommended to counter the
      alarming rise of obesity among AAPI youth. Strategies directed to individual,
      community, and policy levels should emphasize maintenance of healthy traditional
      diets, informed selection of mainstream U.S. foods, and promotion of active
      lifestyles to prevent an impending burden from cancer and nutrition-related
      chronic diseases in AAPI populations.

PMID- 16276537
TI  - Proceedings of the 5th Asian American Cancer Control Academy Community
      Partnerships for Cancer Control: From Vision to Synergy to Reality. Sacramento,
      California, USA, October 22-23, 2004.

PMID- 16276538
TI  - Disparities in colorectal cancer screening rates among Asian Americans and non
      Latino whites.
AB  - Among Asian Americans, colorectal cancer (CRC) is the second most commonly
      diagnosed cancer, and it is the third highest cause of cancer-related mortality.
      The 2001 California Health Interview Survey (CHIS 2001) was used to examine 1)
      CRC screening rates between different Asian-American ethnic groups compared with
      non-Latino whites and 2) factors related to CRC screening. The CHIS 2001 was a
      population-based telephone survey that was conducted in California. Responses
      about CRC screening were analyzed from 1771 Asian Americans age 50 years and
      older (Chinese, Filipino, South Asian, Japanese, Korean, and Vietnamese). The
      authors examined two CRC screening outcomes: individuals who ever had CRC
      screening and individuals who were up to date for CRC screening. For CRC
      screening, fecal occult blood test (FOBT), sigmoidoscopy/colonoscopy, and any
      other form of screening were examined. CRC screening of any kind was low in all
      populations, and Koreans had the lowest rate (49%). Multivariate analysis
      revealed that, compared with non-Latino whites, Koreans were less likely to
      undergo FOBT (odds ratio [OR], 0.40; 95% confidence interval [95% CI], 0.25
      0.62), and Filipinos were the least likely to undergo sigmoidoscopy/colonoscopy
      (OR, 0.62; 95% CI, 0.44-0.88) or to be up to date with screening (OR, 0.68; 95%
      CI, 0.48-0.97). Asian Americans were less likely to undergo screening if they
      were older, male, less educated, recent immigrants, living with >or= 3
      individuals, poor, or uninsured. Asian-American populations, especially Koreans
      and Filipinos, are under-screened for CRC. Outreach efforts could be more focused
      on helping Asian Americans to understand the importance of CRC screening,
      providing accurate information in different Asian languages. Other strategies for
      increasing CRC screening may include using a more family-centered approach and
      using qualified translators.

PMID- 16276539
TI  - English language proficiency and smoking prevalence among California's Asian
      Americans.
AB  - The authors documented California's tobacco control initiatives for Asian
      Americans and the current tobacco use status among Asian subgroups and provide a
      discussion of the challenges ahead. The California Tobacco Control Program has
      employed a comprehensive approach to decrease tobacco use in Asian Americans,
      including ethnic-specific media campaigns, culturally competent interventions,
      and technical assistance and training networks. Surveillance of tobacco use among
      Asian Americans and the interpretation of the results have always been a
      challenge. Data from the 2001 The California Health Interview Survey (CHIS) were
      analyzed to provide smoking prevalence estimates for all Asian Americans and
      Asian-American subgroups, including Korean, Filipino, Japanese, South Asian,
      Chinese, and Vietnamese. Current smoking prevalence was analyzed by gender and by
      English proficiency level. Cigarette smoking prevalence among Asian males in
      general was almost three times of that among Asian females. Korean and Vietnamese
      males had higher cigarette smoking prevalence rates than males in other
      subgroups. Although Asian females in general had low smoking prevalence rates,
      significant differences were found among Asian subgroups, from 1.1% (Vietnamese)
      to 12.7% (Japanese). Asian men who had high English proficiency were less likely
      to be smokers than men with lower English proficiency. Asian women with high
      English proficiency were more likely to be smokers than women with lower English
      proficiency. Smoking prevalence rates among Asian Americans in California
      differed significantly on the basis of ethnicity, gender, and English
      proficiency. English proficiency seemed to have the effect of reducing smoking
      prevalence rates among Asian males but had just the opposite effect among Asian
      females.

PMID- 16276540
TI  - AANCART best practices: cancer awareness activities for Seattle's Combodian
      community.
AB  - Census data indicate that Cambodian Americans are economically disadvantaged and
      linguistically isolated. In addition, cancer registry data show that Southeast
      Asians experience several cancer-related health disparities (e.g., markedly
      elevated risks of cervical and liver cancer). The Seattle regional Asian American
      Network for Cancer, Awareness, Research, and Training (AANCART) site has
      implemented a community-based cancer awareness program for Cambodian immigrants
      in collaboration with a Cambodian community coalition. Our cancer awareness
      program has the following goals: to assist individuals and organizations in
      advocating for a healthy community, to provide information within a cultural
      context, and to deliver information in ways that are useful and meaningful to the
      community. The program was guided by a community assessment that included the use
      of published data as well as information from qualitative interviews, focus
      groups, and quantitative surveys. Examples of community awareness activities
      include group presentations at community-based organizations (e.g., during
      English as a second language classes), health fair participation (including at
      nontraditional venues such as a farmers' market serving Cambodians), and
      educational displays in neighborhood locations (e.g., at Cambodian video stores).
      In addition, the Seattle AANCART site has both inventoried and developed
      culturally appropriate Khmer language cancer education materials and disseminated
      materials through the ETHNO-MED website. Our approach recognizes that limited
      English language proficiency may preclude many Cambodians from understanding
      publicly disseminated information, and Cambodian immigrants are often isolated
      and tend to stay close to their own neighborhoods.

PMID- 16276541
TI  - Tetraphenylborate as a novel bridging ligand in a zwitterionic nickel(I) dimer.

PMID- 16276542
TI  - Lithium alkoxide [Li4O4] cubanes bridged by rhodium-quinonoid
      organometalloligands.

PMID- 16276543
TI  - Tailoring the active site of chemzymes by using a chemogenetic-optimization
      procedure: towards substrate-specific artificial hydrogenases based on the biotin
      avidin technology.

PMID- 16276544
TI  - Decoration of microspheres with gold nanodots--giving colloidal spheres valences.

PMID- 16276545
TI  - Thiooligosaccharide conjugate vaccines evoke antibodies specific for native
      antigens.

PMID- 16276546
TI  - Porous capsules allow pore opening and closing that results in cation uptake.

PMID- 16276547
TI  - Oxindole synthesis through intramolecular nucleophilic addition of
      vinylpalladiums to aryl isocyanates.

PMID- 16276548
TI  - Side-chain orientation and hydrogen-bonding imprint supra-Tau(c) motion on the
      protein backbone of ubiquitin.

PMID- 16276549
TI  - The human T-cell leukemia virus type 1 (HTLV-1): new insights into the clinical
      aspects and molecular pathogenesis of adult T-cell leukemia/lymphoma (ATLL) and
      tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM).
AB  - Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus to be
      identified in the early 1980s. The isolation and identification of a related
      virus, HTLV-2, and the distantly related human immunodeficiency virus (HIV)
      immediately followed. Of the three retroviruses, two are associated definitively
      with specific diseases, HIV, with acquired immune deficiency syndrome (AIDS) and
      HTLV-1, with adult T-cell leukemia/lymphoma (ATLL) and tropical spastic
      paraparesis/HTLV-1-associated myelopathy (TSP/HAM). While an estimated 10-20
      million people worldwide are infected with HTLV-I, infection is endemic in the
      Caribbean, parts of Africa, southwestern Japan, and Italy. Approximately 4% of
      HTLV-I infected individuals develop ATLL, a disease with a poor prognosis. The
      clinical manifestations of infection and the current biology of HTLV viruses with
      emphasis on HTLV-1 are discussed in detail. The implications for improvements in
      diagnosis, treatment, intervention, and vaccination are included, as well as a
      discussion of the emergence of HTLV-1 and -2 as copathogens among HIV-1-infected
      individuals.

PMID- 16276550
TI  - Imitation of artificial membrane system via mobile phases with Tween-80 and
      cholic acid in biopartitioning micellar chromatography.
AB  - The chromatographic behaviour of compounds of biomedical significance was studied
      using micellar mobile phases modified with polyoxyethylene (20) sorbitan
      monooleate (Tween-80). The influence of the surfactant within the 0.75-4%
      concentration range on the retention factor of model compounds was investigated.
      The biological surfactant cholic acid was introduced into the mobile phases in
      order to approach to the structure of natural membranes, viz. erythrocyte and
      cytoplasmatic membranes. It was found that curves of dependence of retention
      factor vs concentration of Tween-80 in the absence and presence of cholic acid in
      the mobile phase considerably diverge with one another, especially in the 2-3%
      concentration range of Tween-80 using C18-type support. Increasing the
      concentration of Tween-80 resulted in the increase of retention factors using
      phenyl-coated stationary phase.

PMID- 16276551
TI  - Number of yolk sacs does not predict amnionicity in early first-trimester
      monochorionic multiple gestations.
AB  - OBJECTIVE: To determine the relationship between amnionicity and number of yolk
      sacs before 11 weeks of gestation. METHODS: Twenty-two cases of monochorionic
      multiple pregnancy were scanned before 11 weeks of gestation. There were 21 sets
      of twins and one of triplets. Amnionicity was determined by visualization of a
      dividing amniotic membrane between the gestational sacs. The number of yolk sacs
      was recorded and compared with the presence or absence of a dividing membrane for
      all fetuses. RESULTS: In 17/20 (85%) cases of monochorionic diamniotic twins, two
      yolk sacs were seen. In 3/20 (15%) cases of monochorionic diamniotic twins, a
      single yolk sac was seen. In the one case of monochorionic diamniotic triplets,
      two yolk sacs were visualized. In one case of monoamniotic twins, a single yolk
      sac was observed. CONCLUSIONS: In monochorionic pregnancies, the presence of two
      yolk sacs predicts diamnionicity. However, the use of the number of yolk sacs as
      a predictor of amnionicity may not be accurate in a small proportion of patients.
      The diagnosis of monoamnionicity can be made only following a careful search for
      a dividing amniotic membrane.

PMID- 16276553
TI  - Gene synthesis on microchips.

PMID- 16276554
TI  - Toward the systematic decomposition of benzene.

PMID- 16276555
TI  - Reactions in micellar systems.
AB  - The notion of "green chemistry" has encouraged even synthetic organic chemists to
      include water as a solvent. Incredible selectivities and activities can be
      achieved through the addition of amphiphiles with a defined structure. The
      morphology of supramolecular assemblies or associates formed by surfactants vary
      according to the temperature and concentration. As a rule, reactions are
      typically conducted using simple spherical aggregates, that is, micelles in the
      nanometer range. The strong polarity gradient present between the hydrophilic
      surface and the hydrophobic core of the micelle means that both nonpolar and
      polar reagents can be solubilized. This solubilization results in reactants
      becoming more concentrated within the micelle than in the surrounding water phase
      and leads to an acceleration of the reaction and causes selective effects. The
      kinetic treatment of reactions in micellar systems can be accomplished by
      considering them as microheterogeneous two-phase systems.

PMID- 16276556
TI  - Architecture and evolution of organic chemistry.

PMID- 16276558
TI  - Chest X-ray quiz. Bilateral pneumothoraces.

PMID- 16276560
TI  - Homozygous hemoglobin C disease.

PMID- 16276559
TI  - The prodromal questionnaire (PQ): preliminary validation of a self-report
      screening measure for prodromal and psychotic syndromes.
AB  - This study aims to establish preliminary validity of the Prodromal Questionnaire
      (PQ), a 92-item self-report screening measure for prodromal and psychotic
      symptoms. Adolescents and young adults (N = 113) referred to a prodromal
      psychosis research clinic completed the PQ and the Structured Interview for
      Prodromal Syndromes (SIPS [Miller, T.J., McGlashan, T.H., Woods, S.W., Stein, K.,
      Driesen, N., Corcoran, C.M., Hoffman, R., Davidson, L., 1999. Symptom assessment
      in schizophrenic prodromal states. Psychiatric Quarterly 70(4), 273-287]), an
      interview with established validity for predicting future psychosis. When
      maximizing selection of true positive cases, scores on a subset of PQ items that
      assess positive symptoms predicted a concurrent prodromal or psychotic SIPS
      diagnosis with 90% sensitivity and 49% specificity. The PQ shows good preliminary
      validity in detecting individuals with an interview-diagnosed prodromal or
      psychotic syndrome, but it is less sensitive to the threshold between prodromal
      and full-blown psychosis.

PMID- 16276561
TI  - Romania's abandoned children are still suffering.

PMID- 16276562
TI  - Russian politicians fight to legislate against "false science".

PMID- 16276563
TI  - Macrophage activation unveiled.
AB  - In the early 1960s, George Mackaness showed that macrophages from mice infected
      with intracellular bacteria could launch an indiscriminate attack against
      unrelated bacteria. Thus began an explosion of research on the biology of what
      Mackaness first termed "macrophage activation."

PMID- 16276564
TI  - Anterior cervico-thoracic osteophytes: an unusual cause of dysphagia.

PMID- 16276566
TI  - ADAP funding and Ryan White Act renewal is delayed by hurricane. HIV patients
      from disaster area spread across U.S.
AB  - AIDS advocates were pessimistic about obtaining enough funding to keep HIV
      patients off waiting lists for the AIDS Drug Assistance Programs (ADAPs) by the
      end of August, and then Hurricane Katrina hit several of the states with the
      worst ADAP funding situation, and changed everything again. Hurricane disaster
      victims have traveled to dozens of states, and those who are HIV infected have to
      start all over with obtaining access to some antiretrovirals. However, despite
      the gloomy outlook, some AIDS advocates say they hope to obtain more funding for
      ADAP and the Ryan White Care Act through an emergency disaster bill.

PMID- 16276565
TI  - Expanding the diagnostic and research toolbox for inborn errors of metabolism:
      the role of magnetic resonance spectroscopy.

PMID- 16276567
TI  - HIV substance abusers encouraged to use new case management program. Study shows
      program works.
AB  - A strength-based case management program for HIV-positive patients who are active
      substance abusers appears to have some success in directing some patients to HIV
      care and treatment, according to recent research. For about 15 years, Ohio
      behavioral scientists have used a strength-based case management model with
      substance abusers, having case managers meet with them over a nine month period
      with the purpose of improving their health care outcomes. What we found in
      summary is, indeed, case management did lead to better outcomes, including less
      involvement in criminal activity and lower levels of drug use, says Richard C.
      Rapp, MSW, assistant professor in the department of community health at School of
      Medicine, Wright State University in Dayton, OH. Rapp also is with the Center for
      Interventions, Treatment and Addiction Research (CITAR) in Dayton. "Case
      management seemed to help keep people in treatment, and longer treatment led to
      better outcomes," Rapp says. "So that's our rallying cry for case management."
      With encouragement from the Centers for Disease Control and Prevention (CDC) of
      Atlanta, GA, Rapp and co-investigators developed a model of strength-based case
      management that was studied in the antiretroviral treatment and access study
      (ARTAS), which ran from 2003 to 2004.

PMID- 16276568
TI  - Researchers study use of the 'MATI' for improving AIDS drug adherence. Early data
      confirm tool's usefulness.
AB  - Investigators have found that an adherence tool that addresses multiple factors
      contributing to adherence difficulties can assist with better adherence. The
      Medication Adherence Training Intervention (MATI) is a newly-invented tool that
      prepares patients for adherence by incorporating medication adherence education,
      the patient's history and medication experiences, with motivation and empowerment
      interventions, says Shvawn McPherson Baker, PharmD, MPH, a research associate in
      the division of hepatology at the University of Miami School of Medicine in
      Miami, FL. "We developed the MATI along the context of clinical pharmacy,
      clinical medication, and clinical psychology, interfacing the three of them to
      come up with an approach to patient care," Baker says. "We looked at how to best
      incorporate the patient's abilities with our abilities." One aspect to the MATI
      that's important is how it is designed to be a nonjudgmental tool that doesn't
      admonish patients for their poor adherence habits, Baker notes. "The approach is
      'Let's take off the white coat and work on this together,'" Baker says. "Let's
      see if there's a readiness for medication adherence and provide education on
      that."

PMID- 16276569
TI  - Italian researcher continues to focus on hydroxyurea treatment for HIV.

PMID- 16276570
TI  - New streamlined risk assessment for HIV clinicians. It's based on CDC report on
      prevention for positives.

PMID- 16276571
TI  - Speed nation. Methamphetamine, HIV, and hepatitis.

PMID- 16276572
TI  - Steps toward change: treating crystal meth dependency. An interview with Yves
      Michel Fontaine by Bob Huff.

PMID- 16276573
TI  - What's the message? Excerpts from two online meth information sources.

PMID- 16276574
TI  - Sources of meth. U.S. Drug Enforcement Administration (DEA).
AB  - The Drug Enforcement Agency (DEA) maintains fact sheets on recent patterns of
      illegal drug sales and use in each state. Here are a few selected reports
      concerning methamphetamine that illustrate the diversity of sources for the drug.

PMID- 16276575
TI  - Meeting meth in the middle.

PMID- 16276576
TI  - Brazil's model approach. Recent international conference highlighted the need to
      partner prevention and treatment in the response to the epidemic.

PMID- 16276577
TI  - Cutting HIV transmission. Male circumcision as a potential HIV prevention
      strategy.

PMID- 16276578
TI  - Making a monkey out of HIV. More is becoming clear about a novel host factor that
      appears central to governing the species-specificity of retroviruses like HIV and
      could be a future antiviral target.

PMID- 16276579
TI  - If you build it, they will pay. A novel incentive called and Advance Market
      Commitment could help spur private sector investment in AIDS vaccine research and
      development.

PMID- 16276580
TI  - Waiting for a breakthrough. An interview with Stephen Lewis. Interview by Kristen
      Jill Kresge.

PMID- 16276581
TI  - CHAVI grant awarded by NIH.

PMID- 16276583
TI  - Plugging the medical brain drain.

PMID- 16276582
TI  - GSK and IAVI collaborate to develop new AIDS vaccine vectors.

PMID- 16276584
TI  - Expanding medical education services.

PMID- 16276585
TI  - Women and HIV.

PMID- 16276586
TI  - Stakeholder consultation to address issues related to tenofovir prophylactic
      research.

PMID- 16276587
TI  - Focus on hepatitis. HCV viremia = poorer immune response to HAART.

PMID- 16276588
TI  - Meeting notes from the 3rd IAS Conference. Male circumcision: a new prevention
      strategy?
AB  - New trial data confirm that male circumcision could substantially reduce
      heterosexual transmission of HIV.

PMID- 16276589
TI  - Meeting notes from the 3rd IAS Conference. Old drugs, new data.
AB  - Researchers reported on the benefits of once-daily tenofovir + FTC + efavirenz as
      initial therapy, described a needle-free injection system for T-20, and announced
      the impending availability of lopinavir/ritonavir in tablet formulation.

PMID- 16276590
TI  - Meeting notes from the 3rd IAS Conference. HIV treatment and risk for metabolic
      complications.
AB  - New studies describe risk factors for diabetes, the metabolic syndrome, and
      dyslipidemia in HIV-infected patients.

PMID- 16276591
TI  - Meeting notes from the 3rd IAS Conference. New drugs.
AB  - CCR5 antagonists created quite a buzz at IAS: several are entering phase III
      trials and could be available in the next 2 to 3 years.

PMID- 16276592
TI  - Meeting notes from the 3rd IAS Conference. Advances in the treatment of
      hepatitis/HIV coinfection.
AB  - New studies address the optimal duration of HCV treatment, early predictors of
      treatment response, and risk factors for liver-related mortality.

PMID- 16276594
TI  - Relief. Hurricane disrupts efforts of AIDS groups.

PMID- 16276593
TI  - Meeting notes from the 3rd IAS Conference. Treating TB and HIV concurrently.
AB  - Several IAS reports focused on strategies for overcoming reduced levels of
      nevirapine due to rifampin coadministration.

PMID- 16276595
TI  - HIV and youth. Study: African-American youth represent new face of AIDS.

PMID- 16276596
TI  - Prisons. PLRA trips up inmate's claim of HIV medication denial.

PMID- 16276597
TI  - Drug pricing. AHF: Schwarzenegger bows to drug industry donations.

PMID- 16276599
TI  - Sentencing. HIV illness does not buy probationer a second chance.

PMID- 16276598
TI  - Transfusion. Botswana's safe blood supply doubles in 2-year period.

PMID- 16276600
TI  - Exposure. HIV-positive biter's guilty plea upheld on appeal.

PMID- 16276601
TI  - Hospital to answer for disclosure of inmate's serostatus.

PMID- 16276602
TI  - India, U.S. AIDS vaccine trials show promise.

PMID- 16276603
TI  - Modern HIV may be slightly less virulent, laboratory study suggests.
AB  - We use this well-publicized research finding as a starting point for discussion
      of different kinds of immune-based therapy.

PMID- 16276605
TI  - New California law: insurers cannot deny organ transplants solely because of HIV.

PMID- 16276604
TI  - Major U.S. treatment-access problems likely: inadequate political response.

PMID- 16276606
TI  - Got Medicare? What people living with HIV need to know about the new Medicare
      drug benefit - "Part D" - starting January 1, 2006.
AB  - Here is practical background on the new drug benefit, for persons on Medicare or
      eligible for it--including details on who can qualify for the major low-income
      help in paying the fees.

PMID- 16276607
TI  - Australia's first religiously affiliated medical school.

PMID- 16276608
TI  - Australia's first religiously affiliated medical school.

PMID- 16276609
TI  - Australia's first religiously affiliated medical school.

PMID- 16276610
TI  - Australia's first religiously affiliated medical school.

PMID- 16276611
TI  - Australia's first religiously affiliated medical school.

PMID- 16276612
TI  - Korean researchers to help others clone cells for study.

PMID- 16276613
TI  - Potential conflicts cited in process for new drugs.

PMID- 16276614
TI  - Genetic catalog may aid search for roots of disease.

PMID- 16276615
TI  - Teaching doctors to be nicer.

PMID- 16276616
TI  - La. investigates allegations of euthanasia at hospital.

PMID- 16276617
TI  - The ethical implications of the targeted population programme proposed by the
      UPA.

PMID- 16276618
TI  - Role of stem cell transplantation in myeloma.

PMID- 16276619
TI  - The future of AIDS and the ethics of seclusion in the face of impending dangers.

PMID- 16276620
TI  - Cadavers for anatomical dissection.

PMID- 16276621
TI  - Exploring the ethics of induced abortion.

PMID- 16276622
TI  - Research with transgendered people.

PMID- 16276623
TI  - The dilemmas of independent researchers.

PMID- 16276624
TI  - The NAS perchlorate review: adverse effects?

PMID- 16276625
TI  - The NAS perchlorate review: is the RfD acceptable?

PMID- 16276626
TI  - Dynamic relationships in community-based research.

PMID- 16276627
TI  - In support of sex selection.

PMID- 16276628
TI  - Treatment of AML in biological subgroups.

PMID- 16276629
TI  - Supreme Court judgement on sterilisations.

PMID- 16276630
TI  - Teachers' views of WHO teaching guidelines on health ethics for undergraduate
      medical education in Bangladesh.

PMID- 16276631
TI  - Ethical quandaries in anthropological fieldwork in psychiatric settings.

PMID- 16276632
TI  - Rapport building and blurring identity.

PMID- 16276633
TI  - Protecting psychiatric patients in research.

PMID- 16276634
TI  - OSHA compliance issues. Styrene overexposure in a bathtub manufacturing facility.

PMID- 16276635
TI  - ICMJE statement on compulsory clinical trial registration: should Indian journals
      follow suit?

PMID- 16276636
TI  - Analytical performance criteria. The U.S. Environmental Protection Agency
      Environmental Technology Verification Program--an overview.

PMID- 16276637
TI  - The reference guide: a step-by-step technique for restoration of fractured
      anterior permanent teeth.

PMID- 16276638
TI  - Impact of life-prolonging technologies on end-of-life care in India.

PMID- 16276640
TI  - Socio-ethical issues in the deployment of life-extending technologies.

PMID- 16276639
TI  - Issues in the care of the dying.

PMID- 16276641
TI  - Point of Care.

PMID- 16276643
TI  - Change in tensile properties of neoprene and nitrile gloves after repeated
      exposures to acetone and thermal decontamination.
AB  - This study investigated the change in tensile properties of neoprene and nitrile
      gloves after repeated cycles of exposure to acetone, followed by thermal
      decontamination. The glove was exposed to acetone (outer surface in contact with
      chemical), subjected to thermal decontamination, and tested for the tensile
      strength and the ultimate elongation. Thermal decontamination was carried out
      inside an oven for 16 hours at 100 degrees C. The exposure/decontamination
      procedure was repeated for a maximum of 10 cycles. For neoprene versus acetone,
      the mean tensile strength consistently decreased after each
      exposure/decontamination cycle. Multiple comparisons indicated that the mean
      tensile strengths between the new swatches and each exposure/decontamination
      group were significantly different (p < 0.05). The loss of either tensile
      strength or ultimate elongation was less than 23% compared with new swatches
      after four exposure/decontamination cycles. Swatches with out acetone exposure
      were then cycled through the oven in the same manner. It was found that both the
      heat used for thermal decontamination and acetone exposure significantly affected
      the tensile strength and ultimate elongation. For nitrile gloves exposed to
      acetone, the mean tensile strength remained virtually unchanged (p > 0.05). The
      mean tensile strength for the new swatches was 37.1 MPa and the mean tensile
      strength after nine exposure/decontamination cycles was 36.0 MPa, with a loss
      less than 3%. The largest single cycle loss for ultimate elongation occurred
      during the first exposure/decontamination cycle for both glove materials. In our
      previous study, decisions regarding the effectiveness of the decontamination
      process were based on having no discernible change in the breakthrough time and
      steady-state permeation rate. The results of this study indicate that the
      effectiveness of the decontamination process cannot be based on permeation
      parameters alone but must also take into account the change in physical
      properties.

PMID- 16276642
TI  - End-of-life issues neglected in India.

PMID- 16276644
TI  - Issues faced by a hospice.

PMID- 16276645
TI  - Day-to-day decision making as a physician in India.

PMID- 16276647
TI  - Any dose is too high.

PMID- 16276646
TI  - Practicing medicine in India: some ethical dilemmas.

PMID- 16276648
TI  - This is YourAir calling.

PMID- 16276649
TI  - The radical theory of sneezing.

PMID- 16276650
TI  - Living donor liver transplantation.

PMID- 16276652
TI  - Improving quality of care through systems research: a guide for managers and
      practitioners.

PMID- 16276651
TI  - Response: living donor liver transplantation.

PMID- 16276653
TI  - Understanding and optimizing human development: from cells to patients to
      populations. Proceedings of the National Institute of Child Health and Human
      Development 40th Anniversary Scientific Symposium, September 8, 2003, Bethesda,
      Maryland, USA.

PMID- 16276654
TI  - Assignment of the bovine BCL2-like 2 gene (BCL2L2) to BTA10q15-->q21 by in situ
      hybridization and with somatic cell hybrids.

PMID- 16276655
TI  - Assignment of cellular retinoic acid-binding protein 1 (CRABP1) and 2 (CRABP2) to
      porcine chromosome 7q12-->q23 and 4q21-->q23 by somatic cell and radiation hybrid
      panel mapping.

PMID- 16276656
TI  - Assignment of BReast Cancer Associated 1 (BRCA1) to tammar wallaby (Macropus
      eugenii) chromosome 2q3 by in situ hybridization.

PMID- 16276657
TI  - President's message: Interdisciplinary education in the health sciences.

PMID- 16276658
TI  - Takotsubo-like ventricular dysfunction and coronary microvascular dysfunction:
      fulminant cardiac syndrome X?

PMID- 16276659
TI  - Medical ethics in surgical wards: knowledge, attitude and practice of surgical
      team members in Karachi.
AB  - A survey was undertaken to assess the knowledge, attitude and practice of medical
      ethics among surgical residents and interns in three teaching hospitals of
      Karachi, Pakistan. 101 out of 120 completed responses were included in the study.
      Fifty-one respondents had heard about the Code of Ethics formulated by the
      Pakistan Medical and Dental Council. Forty-four had read the code. Seven had no
      knowledge about it. Forty-seven reported taking consent for procedures. Forty-two
      respondents gave correct answers on questions of confidentiality and knowledge of
      law pertaining to trauma victims. Only 11 reported having been taught ethics as
      students. Four did not feel the need of its teaching at an undergraduate level.
      Doctors graduating within the last 10 years gave fewer correct answers than those
      graduating earlier. Knowledge of medical ethics and its application on the
      surgical floors is extremely poor. The survey results support the view that
      medical ethics should be part of the undergraduate medical curriculum.

PMID- 16276660
TI  - The Terry Schiavo case: possible implications for India.

PMID- 16276661
TI  - Ethical and juridical foundations of conscientious objection for health care
      workers.
AB  - In front of the evolution of medicine and biotechnology, health care workers are
      called upon to take part within new biomedical practices, that may overcome the
      limit of acceptability, as it is perceived by their moral conscience. Issues as
      abortion, euthanasia, assisted suicide, artificial fertilisation, experimentation
      on human embryos and prescription of contraceptives and abortifacients call into
      play the right to conscientious objection of health care personnel, and in some
      cases, perhaps of physicians and pharmacists too. This recall--already present in
      many codes of professional conduct and medical ethics--sounds today as a
      necessity, which asks for a serious deepening of the content, the applicability
      and the new hypothesis of conscientious objection, in the light of bioethics and
      law. In particular, the self-determination and often exasperated autonomy of the
      patient within these practices makes a new principle of professional integrity
      arise, to protect the physician's conscientious convictions, if the request of
      the patient or society seem to violate some fundamental human values.

PMID- 16276662
TI  - Establishment and work of ethics committees in central and eastern European
      countries.
AB  - The genuine reform efforts in medicine and health care in Central and East
      European (CEE) countries have continued to pose important and thought-provoking
      challenges to the newly reborn disciplines of medical ethics (or bioethics). They
      are embodied in the bulk of new ethical problems, concepts and quandaries brought
      about by the developments, changes, clashes, and "real life" issues of the CEE
      countries' health care systems and biomedical sciences. Certain part, quite
      variable from country to country, of this bio-ethical endeavour has been confined
      to the work and activities of ethics committees (ECs) or similar bodies. They
      have emerged in varying number, shape, composition, competence, legal status,
      responsibility and time of appearance, in almost all transition countries of CEE.
      They may be considered as a kind of "field workplaces" of medical
      ethics/bioethics within the countries' HCSs or biomedical research structures.
      Despite some shortcomings and drawbacks, a lot has already been achieved. In some
      countries the progress has been quick and systematic. The major pitfalls were
      mostly due to the missing, weak or unclear legal backing of ECs' establishment
      and work; lack of education and training of their members; insufficient support
      from health care administrators; misconceptions concerning their mission,
      procedures, scope of responsibility, and reporting; insufficient or missing
      funding; low profile societal esteem for ECs' work; but some drawbacks were due
      also to the underdeveloped 'dialogic' culture of the impartial discussion and
      democratic discourse in the 'post-totalitarian' CEE transition countries. The
      future of ECs in CEE will be connected to the countries' integration and
      harmonization efforts towards research, health systems, and other international
      structures in Europe and beyond. This should need an extensive and non
      discriminatory international partnership, exchange and co-operation.

PMID- 16276663
TI  - Directive 2001/20/EC of the European Parliament and of the Council of 4 April
      2001 on the approximation of the laws, regulations and administrative provisions
      of the member states relating to the implementation of good clinical practice in
      the conduct of clinical trials on medicinal products for human use.

PMID- 16276664
TI  - Review of publications.

PMID- 16276665
TI  - Cash and compassion.

PMID- 16276666
TI  - Why fetuses don't feel pain.

PMID- 16276667
TI  - Privacy and prejudice: whose ID is it anyway?

PMID- 16276668
TI  - End-of-life decisions: ethical principles.

PMID- 16276669
TI  - A fragile gift: sharing and saving life through embryo adoption.

PMID- 16276670
TI  - Earning points for moral behavior: organ allocation based on reciprocity.
AB  - Anticipating the reevaluation of the Dutch organ procurement system, in late 2003
      the Rathenau Institute published a study entitled 'Gift or Contribution?' In this
      study, the author, Govert den Hartogh, carries out a thorough moral analysis of
      the problem of organ shortage and fair allocation of organs. He suggests there
      should be a change in mentality whereby organ donation is no longer viewed in
      terms of charity and the volunteer spirit, but rather in terms of duty and
      reciprocity. The procurement and allocation of donor organs should be seen as a
      system of mutually assured help. Fair allocation would imply to give priority to
      those who recognize and comply with their duty: the registered donors. The idea
      of viewing organ donation as an undertaking involving mutual benefit rather than
      as a matter of charity, however, is not new. Notwithstanding the fact that
      reference to charity and altruism is not required in order for the organ donation
      to be of moral significance, we will argue against the reciprocity-based
      scenario. Steering organ allocation towards those who are themselves willing to
      donate organs is both an ineffective and morally questionable means of attempting
      to counter organ shortage.

PMID- 16276671
TI  - Facing immortality.
AB  - This study is primarily a call to philosophers to attend the concerns raised by
      the increasing possibility of indefinitely extended human life. While these
      concerns are largely moral and socio-political, questions arising from this
      possibility are seen to involve other philosophical areas, including
      epistemology. Starting with the age-old desire for extended, enjoyable life,
      possible strategies for realizing such life are considered. Such realization is
      shown to conflict with the desire for children. Various reasons for choice
      between the alternatives of indefinitely extended life and what is currently
      understood to be a normal life, including the possibility of offspring, are
      examined. Competing social visions are sketched for the purpose of resolving this
      dilemma. It is argued that humanity's likely choice from among the competing
      social sketches favors the decision for extended life against that for limited
      lifespan with the possibility of children. Assuming that the extended life will
      be a life of learning leads to epistemological considerations regarding what is
      to be learned.

PMID- 16276672
TI  - Biocentric ethics and animal prosperity.
AB  - Singer's utilitarian and Regan's deontological views must be rejected because:
      (1) they rely on criteria for moral standing that can only be known a priori and
      (2) if these criteria were successful, they'd be too restrictive. I hold that
      while mental properties may be sufficient for moral standing, they are not
      necessary. (3) Their criteria of moral standing do not unambiguously abrogate
      needless harm to animals. I defend a theory of biocentric individualism that
      upholds the principle of species egalitarianism while at the same time
      recognizing that in certain cases, human needs must outweigh the needs of non
      humans. On this view, moral consideration is not conferred only on beings that
      have human-life mental properties. Finally, it offers an unambiguous
      recommendation for the abolition of harmful animal experimentation, factory
      farming, and killing animals for sport.

PMID- 16276673
TI  - "Efficacy Outcome Variables for the Evaluation of Periodontal Disease Treatment"
      Expert Panel Symposium. Chapel Hill, North Carolina, USA, 28 January 2005.

PMID- 16276674
TI  - [The contribution of physics to human health and biomedicine: on occasion of the
      International Year of Physics].

PMID- 16276675
TI  - [An outlook on the application of medical physics in cancer therapy].

PMID- 16276676
TI  - [A fatal free floating thrombus in left atrium].
AB  - An 81 year old woman, diagnosed with rheumatic mitral valve disease and atrial
      fibrillation ten years previous, was admitted due to a right carotid transient
      ischemic attack and a acute coronary syndrome. No ST elevation was noted in the
      region supplied by the anterior descending artery coronary (troponin T increased
      and anterolateral negative waves T). In recent years years, she had maintained
      with (anticoagulants) an INR of 2.5-3.5; however, in the previous month the INR
      had dropped to 1.8. The transthoracic echocardiography showed an anterolateral
      hypokinesis and a globular hyperechoic mass of 2 x 4 cm which appeared to be a
      free floating thrombus in the dilated left atrium. This occasionally caused
      occlusion of the mitral valve, which itself had a severe rheumatic stenosis of
      approximately 1 cm2. Due to the high risk of occlusion of the mitral valve and
      systemic embolisms, the mitral valve replacement and thrombectomy was recommend
      to the patient. The patient refused this treatment and subsequently died 5 days
      later. This case emphasizes the importance of a suitable level of anticoagulation
      (INR between 2,5 and 3,5) in patients with mitral stenosis and chronic atrial
      fibrillation. These cases have a the high risk of thromboembolism, and urgent
      surgery is mandatory when a free floating left atrial thrombus is observed.

PMID- 16276677
TI  - [Possible health effects associated with Pre-Columbian metallurgy].
AB  - In the Old World, several researchers have indicated that adverse health effects
      were associated with exposure to arsenic, and that this influenced a change in
      the use of copper-arsenic alloys to others less toxic. This hypothesis was
      evaluated for three Pre-Columbian metallurgy traditions: Central Andes,
      Intermediate Area, and West Mexico. The metal artifacts from the Central Andes
      showed arsenic concentrations similar to those in the Old World (0.5%-1.0%). In
      the Intermediate Area the values were smallest; however, in West Mexico the
      arsenic content was very high (7%-25%). In Central Andes arsenical bronze was
      used initially, but copper-tin alloys when introduced were preferred and
      distributed throughout the Inca Empire. Osteological and artistic evidences of
      foot amputations among Moche individuals from Central Andes support the presence
      of "black foot disease" (a condition associated with arsenic poisoning) among Pre
      Columbian populations. In conclusion, the adverse effects of arsenic have been
      observed in the New World, and that these effects promoted a change toward the
      use of less toxic alloys.

PMID- 16276678
TI  - [Experimental infection of the gerbil (Meriones unguiculatus) by Colombian
      isolates of Giardia duodenalis].
AB  - INTRODUCTION: Natural and experimental Giardia infections have been reported from
      bovines, equines, goats, canines, felines and rodents such as mice, rats and
      gerbils. The latter have provided successful animal models for Giardia duodenalis
      and Giardia muris experimental infections. OBJECTIVE: The gerbil model was used
      to establish the pattern of infection of Colombian Giardia human isolates.
      MATERIALS AND METHODS: Giardia cysts were obtained from stool specimens of
      symptomatic giardiasis patients by means of sucrose-percoll gradients. Animal
      inoculation was performed by gastric intubation and injection with 5 x 10(3)
      Giardia cysts. The course of infection was established by counting cysts every
      day and trophozoites weekly throughout a period of 30 days. RESULTS: The pattern
      of cyst excretion was found to be intermittent. Cysts were released during the
      second and third weeks of infection but not during the first or fourth weeks. The
      mean minimal number of cysts released per 2-hr collection period was 79 and the
      mean maximum number was 17,943. Colonization of the small intestine by
      trophozoites was observed with a mean number ranging from 15,000 to 6,577,778
      trophozoites/ml. DISCUSSION AND CONCLUSIONS: Gerbils inoculated with G.
      duodenalis isolates obtained from geographical areas outside Colombia resolved
      the infection between 86 and 114 days after infection, whereas gerbils infected
      with Colombian G. duodenalis isolates resolved the infection at 30 days. The
      gerbil proved to be a good animal model for experimental infection with Colombian
      isolates of G. duodenalis. Experimental Giardia infection of gerbils permit a
      sufficient yield of cysts and trophozoites to be used as antigens for the
      immunization of other animals and to obtain Giardia antibodies that could be used
      for Giardia antigen detection assays in stool specimens.

PMID- 16276679
TI  - [Detection mutations in the DNA mismatch repair genes of hMLH1 and hMSH2 genes in
      Colombian families with suspicion of hereditary non-polyposis colorectal
      carcinoma (Lynch syndrome)].
AB  - INTRODUCTION: Colorectal cancer (CRC) is the second highest cause of cancer
      mortality in developed countries. In Colombia, CRC ranks fifth as a cause of
      cancer death. Approximately 75% of CRC appear to be spontaneous and 25% are
      familial, with 5% of the latter clearly hereditary. Of these, hereditary non
      polyposis colorectal carcinoma (HNPCC)-or Lynch syndrome is the most important.
      OBJECTIVE: Herein, the two most important genes involved in Lynch syndrome, the
      hMLH1 and hMSH2 were analyzed for presence of mutations. MATERIALS AND METHODS:
      Seventeen Colombian families that fulfilled the Amsterdam II criteria or Bethesda
      guidelines for Lynch syndrome were selected. The of 35 exons of hMLH1 and hMSH2
      genes were screened by SSCP and those with electrophoretic variants were
      sequenced. RESULTS: Eight germinal mutations were detected, corresponding to a
      47% detection mutation rate. Six of the eight mutations have previously been
      reported. These consisted of the following mutations: a single base substitution
      at the donor splicing site of exon 9, a single base substitution (A>G) at codon
      755 of the exon 17, and another single base substitution (G>A) at codon 681 of
      exon 18. The two novel mutations consisted of a single base substitution (C>T) at
      codon 640 of exon 17 of the hMLH1 gene and a two-nucleotide deletion (TG) at
      codon 184 of exon 3 of hMSH2 gene. In addition, two families were observed with a
      polymorphism in the intron 13 (G>A) nt 1558+14, of hMLH1 gene. CONCLUSIONS: This
      study represented the first survey for detecting mutations associated with Lynch
      syndrome in Colombia, and is intended to lead to the establishment of a
      management and prevention program.

PMID- 16276681
TI  - [Cytotoxicity and genotoxicity of human cells exposed in vitro to glyphosate].
AB  - INTRODUCTION: Glyphosate is a broad-spectrum non-selective herbicide, used to
      eliminate unwanted weeds in agricultural and forest settings. Herbicide action is
      achieved through inhibition of aromatic amino acid biosynthesis in plant cells.
      Since this is not a conserved mechanism between human and plant cells, glyphosate
      is considered to be a low health risk substance for humans. However, the
      occurrence of possible harmful side effects of glyphosate use is not well
      documented and controversial. Toxicity and genotoxicity studies indicate that
      glyphosate is not harmful, although several investigations suggest that it can
      alter various cellular processes in animals. Therfore this has potential as a
      health and environmental risk factor in areas where glyphosate is widely used.
      OBJECTIVES: The present study evaluated glyphosate cytotoxic and genotoxic
      effects in normal human cells (GM38) and human fibrosarcoma (HT1080) cells.
      MATERIALS AND METHODS: Acute and chronic cytotoxicity were determined through the
      exposure of cultured cells to graded concentrations of glyphosate, and cell
      viability analysis was performed with crystal violet and Trypan blue staining.
      Genotoxicity was determined using the comet assay and data significance was
      evaluated with Dunnet's test. RESULTS: For chronic cytotoxicity a dose-dependent
      effect was observed in both GM38 and HT1080 cells after treatment with 5.2-8.5 mM
      and 0.9-3.0 mM glyphosate, respectively. In the acute cytotoxicity study, GM38
      cells exposed to 4.0-7.0 mM glyphosate and HT1080 cells exposed to 4.5-5.8 mM
      glyphosate, had cell viability counts higher than 80%. Genotoxic effects were
      evidenced in GM38 cells at glyphosate concentrations of 4.0-6.5 mM and in HT1080
      cells at glyphosate concentrations of 4.75 -5.75 mM. CONCLUSIONS: The levels of
      cytotoxicity and genotoxicity of glyphosate occurring in mammalian cells
      suggested that its mechanism of action is not limited to plant cells.

PMID- 16276680
TI  - [BabA2, oipA and cagE Helicobacter pylori genotypes in Colombian patients with
      gastroduodenal diseases].
AB  - INTRODUCTION: Helicobacter pylori infection is associated with the development of
      several gastroduodenal diseases. Bacterial virulence genes have been found
      associated with an increased risk for gastric disease. OBJECTIVES: Herein,
      associations were made between the presence of vacA, cagA, cagE, babA2 and oipA
      genes in H. pylori isolates and the range of clinical consequences of the
      infection. METHODS: PCR was used to amplify vacA, cagA, cagE, babA2 and oipA
      genes in 166 isolates-50 patients with peptic ulcer, 39 with non-atrophic
      gastritis, 26 with atrophic gastritis, 26 with intestinal metaplasia and 25 with
      gastric adenocarcinoma. RESULTS: cagA, cagE, babA2 and oipA genes were found in
      73%, 75%, 48% and 74% of isolates, respectively. The cytotoxic vacA s1m1/cagA
      positive/cage positive genotype was present in 64% (100/157) of isolates. A
      higher frequency of cytotoxic strains was observed in cancer patients (84%),
      intestinal metaplasia (91%) and peptic ulcer (81%) in comparison with gastritis
      patients (50%) (p=0.002, 0.008, 0.007, respectively). The oipA and babA2
      frequency was higher in cytotoxic isolates than in non-cytotoxic isolates (oipA:
      81% vs. 52%, P=0,003; babA2: 58% vs. 12% (p<0.001). No significant association
      was found among clinical outcomes and oipA or babA2 genotypes, analyzed alone or
      in combination with vacA and cagA. CONCLUSION: Therefore, babA2 or oipA genes are
      not marker indicators of ulcer or cancer.

PMID- 16276682
TI  - [Prevalence of intestinal helminths in dogs from Quindio Province].
AB  - BACKGROUND: Intestinal helminths are pathogens for domestic animals and provide a
      source of potential infection for humans. OBJECTIVES: The prevalence of
      intestinal helminths in domestic dogs was determined in a province-wide survey in
      Quindio Province, Colombia. MATERIALS AND METHODS: The sample size was calculated
      based upon the data of the 2003 antirabies vaccination program in Quindio.
      Information in the form of an epidemiological questionnaire was provided by dog
      owners. Fecal samples from dogs were analyzed by Ritchie's concentration method.
      RESULTS: Of 324 samples, 67.6% were from purebred dog races and 32.4% were
      mongrels. A 22.2% prevalence for intestinal helminthes was found. Ancylostoma
      caninum was the most prevalent parasite (13.9%), followed by Trichuris vulpis
      (4.3%), Toxocara canis (2.5%), and Strongyloides stercoralis (4.0%).
      Multiparasite infestations were observed in 2.46% of the dogs. CONCLUSION:
      Presence of parasites was strongly correlated with age and degree of association
      with the open streets. Control programs are recommended for helminth surveillance
      in human and canine populations.

PMID- 16276683
TI  - [Presence and viability of Giardia spp. and Cryptosporidium spp. in drinking
      water and wastewater in the high basin of Bogota river].
AB  - INTRODUCTION: Faecal contamination in wastewater and drinking water is linked to
      the dissemination of water related diseases. The bacteria, virus and parasites
      present in drinking water are responsible for substantial morbidity and
      mortality, especially among infants. Giardia spp. and Cryptosporidium spp. were
      the organisms selected as parasite contamination indicators. Their presence
      serves as a useful tool for evaluating water quality and determining sanitary
      risk. At present, in Colombia, concentration and occurrence of these parasites is
      unknown and an immediate assessment was considered necessary. OBJECTIVE:
      Protozoan presence was determined in five sampling stations in the Bogota river
      upper basin and in two drinking water plants near the same area. MATERIALS AND
      METHODS: The techniques applied for counting encysted forms consisted of
      inorganic flocculation for wastewater or filtration for drinking water.
      Fluorogenic vital dyes tested for viability. RESULTS: The presence of
      Cryptosporidium spp. was confirmed in two of the sampled stations and at two of
      the drinking water plants. Giardia spp. was found at two of the drinking water
      plants but not at the sampled stations. Viable cysts were found for
      Cryptosporidium spp. in one of the samples from the Bogota river, but only
      inviable exemplars were obtained from the drinking water plants. CONCLUSIONS: The
      results revealed protozoan presence in drinking and residual water implying the
      presence of a potential sanitary hazard.

PMID- 16276684
TI  - [Validation of a questionnaire to assess the quality of health information in
      Argentinian newspapers].
AB  - INTRODUCTION: The daily press is an important source of health information and
      may influence health care utilization. However, medical reports published in
      newspapers from developed countries have shown a poor quality. OBJECTIVES: The
      reliability of the questionnaire Index of Scientific Quality was evaluated by
      using it to measure the scientific quality of health information published by
      Argentinian newspapers between 2000 and 2002. It assessed the readability of the
      texts in grade levels and explored the relationship between quality and other
      factors. MATERIALS AND METHODS: The Spanish adaptation of the instrument
      consisted in translation, back-traslation and pilot study. The reliability was
      assessed by applying the instrument to newspaper articles with more than 300
      words that discussed therapy, diagnosis, prevention, lifestyle effects, and
      hazardous exposure. Two physicians independently graded 129 articles. Inter
      observer and intra-observer concordance was quantified for each item with the
      intra-class correlation coefficient (CI95%). To measure scientific quality, a
      randomized sample of 210 articles was assessed. Each received a mark that ranged
      from 0 to 100. Readability was determined by the FRY graph method. The
      relationship between quality and other variables was explored with multiple
      linear regression analysis. RESULTS: The inter-rater concordance varied between
      0.48 (0.34-0.61) and 0.67 (0.56-0.75). Intra-rater concordance varied from 0.51
      (0.37-0.63) to 0.95 (0.93-0.96). The internal consistency (Cronbach's alpha) was
      0.88. The quality-of-health-information was rated at 25 points (16.7, 33.3)
      [median (intercuartil range)]. The reading level was assessed to be at the 10.4
      grade (10.2-10.6) [mean (CI 95%)]. CONCLUSIONS: Quality of the health information
      was greatly deficient; however, no specific factors were related with quality.
      Readability was probably a key barrier for access to the health information.

PMID- 16276685
TI  - [Pesticides use by flower companies associated with the Colombian Association of
      Flower Exporters].
AB  - INTRODUCTION: In Colombia, pesticide exposure has became a public health problem,
      as the use of these substances continues to increase. OBJECTIVE: The current
      study accumulated information concerning pesticides used by flower companies in
      Bogota and Rionegro (Antioquia) that were associated with Asociacion Colombiana
      de Exportadores de Flores (Asocolflores) in Colombia. MATERIALS AND METHODS:
      Eighty-four companies were stratified by geographic location and size. Company
      and worker information was collected, and for each company, the process of
      pesticide application and maintenance of the cultivated flowers was carefully
      observed. Univariate and bivariate, and correlation analyses were applied for
      data analysis. RESULTS: Sex of workers was 39.4% male and 60.6% female.
      Pesticides were grouped into 4 toxicity classes: 14.3% were class I, 14.4% class
      II, 52.0% class III, and 19.2% class IV. Dithiocarbamates was the group of
      pesticides more commonly used (11.7%). The equipment most frequently used for
      pesticide application was the "bomba movil" (92.8%), and the "lanza" (92.9%).
      Cholinesterase activity measured by the Michel-Aldrige method was the biological
      marker for exposure to pesticides used in 85.9% of the companies. Recommendations
      for improvements in their use and for measures to further reduce exposure of
      workers are made.

PMID- 16276686
TI  - [Isolation of Cryptococcus gattii serotype B from detritus of Eucalyptus trees in
      Colombia].
AB  - INTRODUCTION: Cryptococcus gattii serotype B has been associated with several
      species of trees in tropical and subtropical regions. Serotype B has been found
      to be the second most frequently isolated from patients in Colombia, but it has
      not been isolated from the environment. Therefore, a study was designed to sample
      plant material from a forest in the province of Cundinamarca, with the aim of
      establishing the presence and distribution of the C. neoformans complex,
      specially serotype B. In addition, isolates were evaluated for several phenotypic
      characteristics associated with virulence. METHODOLOGY: During February and
      March, 2003, 4 separate sample collections were made. One hundred sixty-seven
      samples were collected from detritus of eucalyptus and 28 samples from other
      species of trees. All were processed using the conventional procedure and plated
      on selective media. The following parameters were measured: cellular and capsular
      sizes in the filtrates, growth at 37 degrees C, virulence in a mouse animal model
      system, and mating type as detected by PCR. RESULTS: Cryptococcus gattii serotype
      B was isolated from 46 eucalyptus samples (27.5%). The cellular size in the
      filtrates ranged from 3.10 to 4.15 microm and the capsular size from 0.30 and
      0.46 microm. The 46 isolates grew at 37 degrees C, but none of them caused the
      death in the animals during 70-day observation period. All isolates were of
      mating type a. CONCLUSIONS: This constitutes the first report of the isolation of
      serotype B, mating type a, from eucalyptus detritus in Colombia.

PMID- 16276687
TI  - [Evaluation of time-to-pregnancy as a measure in environmental epidemiology].
AB  - Since the late 80's, time to pregnancy has been used in environmental
      epidemiology to explore adverse effects of different exposures. The advantages of
      this measure and additional elements to be considered in the performance of this
      type of studies are reviewed. Study design includes the following steps:
      population selection, sample size, outcome measurement, statistical analyses and
      sources of bias. Guidelines were suggested for the properly development of this
      type of study.

PMID- 16276688
TI  - [Evaluation of the World Health Organization clinical definition of dengue].
AB  - INTRODUCTION: The distinction between dengue and other acute febrile diseases is
      difficult when based solely on symptoms. OBJECTIVE: An attempt was made to
      evaluate usefulness of dengue diagnoses in an endemic area (Bucaramanga,
      Colombia), based on the definitions recommended by the World Health Organization.
      MATERIALS AND METHODS: In a cohort >12 years of age with indications of acute
      febrile illness, the sensitivity, the specificity and the predictive values were
      determined based on the WHO dengue definition. Two or more of the following
      symptoms were included: headache, retroorbital pain, myalgia, arthralgia, rash,
      hemorrhagic manifestations, or leucopenia. RESULTS: One hundred-one cases of
      dengue and 89 patients with acute febrile illness were enrolled in the study. The
      dengue cases were confirmed by serological or by virus presence. The WHO case
      definitions showed sensitivity, 99%; specificity, 1%; positive predictive value,
      53%, and negative predictive value, 50%. CONCLUSION: This clinical definition
      demonstrated high sensitivity, but a low specificity. Therefore, the clinical
      definition was useful for screening, but it did not differentiate between dengue
      and other febrile diseases.

PMID- 16276689
TI  - [First report of Triatoma nigromaculata (Stal, 1859) (Hemiptera, Reduviidae,
      Triatominae) for Colombia].
AB  - The presence of Triatoma nigromaculata was recorded for the first time in
      Colombia in the rural village La Playa in the province of Cauca. A single female
      was captured from an outdoor area near a household. The presence of Trypanosoma
      parasites in the specimen was not established due to the poor condition of the
      specimen. The epidemiological importance of this finding is discussed with
      respect to the potential for transmission of Chagas disease in the province of
      Cauca and, more broadly, in Colombia.

PMID- 16276690
TI  - [Serological tests in the diagnosis of tuberculosis].

PMID- 16276691
TI  - The position and dimensions of the mental foramen in adult Malawian mandibles.
AB  - BACKGROUND: The mental foramen is found on the anterolateral aspect of the
      mandible and transmits the mental nerve and vessels. The identification and
      actual location of this foramen is very important in clinical dentistry as well
      as in the microscopic and macroscopic evaluation of the morphology and maturity
      of the human mandible. METHODOLOGY: We determined the position and dimensions of
      this foramen from seventy adult indigenous Malawian mandibles of both sexes. The
      shape, number and orientation of the mental foramen were determined by visual
      examination and its transverse and vertical diameters measured using a digital
      venier caliper. RESULTS: In the majority of cases, the mental foramen was oval in
      shape, oriented posterosuperiorly, and bilaterally symmetrical. The modal
      position of the foramen with respect to the mandibular teeth was inferior to the
      second premolar tooth. Its vertical position was slightly below the midpoint of
      the distance between the lower border of the mandible and the alveolar margin.
      CONCLUSION: The shape and orientation of the mental foramen shown in our study
      correspond to what have been documented in most previous studies. However,
      variations do exist in the modal position of this foramen in different population
      groups. We therefore stress the importance of palpation of the foramen during
      administration of local anaesthesia and in the interpretation of radiographs
      prior to surgery.

PMID- 16276693
TI  - Management of ectopia vesica in Ibadan: an 8-year review.
AB  - CONTEXT: The management of children with ectopia vesica is intricate and complex.
      Repair of the bladder soon after delivery is desirable, particularly in our
      environment as the social stigma associated with such an anomaly can lead to
      child abandonment or infanticide. OBJECTIVE: To report our experience in the
      management of children with ectopia vesica at the University College Hospital
      (UCH), Ibadan, over an 8-year period. STUDY DESIGN, SETTING AND SUBJECTS: All
      children who presented at the UCH, Ibadan between January 1995 and December 2002
      with ectopia vesica had the bladder closed primarily. The children that presented
      between 1995 and 1998 had the symphysial diastasis approximated with no. 1 nylon
      suture, while those that presented subsequently had the muscle and fascial layer
      closed with a darning suture of no. 1 nylon. RESULT: A total of 13 children
      presented with ectopia vesica during the period of the study. The bladder was
      closed in all cases. Abdominal wound dehiscence occurred less frequently in
      patients who had darning suture approximation of the muscle and fascial layer,
      compared with those who had simple symphysial approximation with nylon suture.
      CONCLUSION: The result of immediate bladder closure in children with ectopia
      vesica can be satisfactory in this environment. There is a need for continuing
      experience in the management of these children to improve outcome.

PMID- 16276692
TI  - Comparison of the efficacy and safety of budesonide turbuhaler administered once
      daily with twice the dose of beclomethasone dipropionate using pressurised
      metered dose inhaler in patients with mild to moderate asthma.
AB  - BACKGROUND: Current treatment guidelines have clearly defined the central place
      and benefits of inhaled glucocorticoids in the management of bronchial asthma.
      However, compliance with therapy is often poor due to complexity of treatment
      regimens. Therefore, a single once daily regimen with a simple device, the
      turbuhaler might be expected to result in improved compliance and better
      efficiency. STUDY DESIGN: This was a prospective open randomized trial with
      parallel groups conducted in five tertiary medical institutions. Asthmatic
      patients who met the enrolment criteria were randomized to receive either
      budesonide 400 microg daily or beclomethasone dipropionate 400 microg twice daily
      for eight weeks. RESULT: At the end of the study, both drugs were found to be
      effective in reducing the symptoms of asthma, reduction of beta2 agonist usage
      and improvement in lung function tests. However Budesonide Turbuhaler provided
      better effects in all parameters (p < 0.05). Both drugs were well tolerated.
      CONCLUSION: It is therefore concluded that Budesonide Turbuhaler administered
      once daily at a dose of 400 microg is more efficacious than Beclomethasone
      dipropionate 400 microg twice daily administered via pressurized metered dose
      inhaler.

PMID- 16276694
TI  - Morphometric and stereological assessment of the effects of long-term
      administration of quinine on the morphology of rat testis.
AB  - BACKGROUND AND OBJECTIVES: Quinine (QU) has been used worldwide in the
      suppression and treatment of malaria for more than 350 years. The aim of this
      study was to determine the long-term morphological response of the testis to long
      term administration of QU using stereological parameters. MATERIALS AND METHODS:
      64 adult male Sprague-Dawley rats weighing 180-200g were used. The animals were
      randomly divided into 8 groups of 8 rats each. Every experimental animal had
      intramuscular QU at a dose of 10mg/kg body weight per day (5 times in a week,
      with the exception of group 1 animals). Group 1 rats had QU for 1 week (7 days
      consecutively) and were sacrificed on the last day of injection. Groups 2 and 3
      rats had QU for 4 and 6 weeks and were sacrificed at the end of the 4th and 6th
      week respectively. Group 4, 5, 6 and 7 rats had QU for 8 weeks and were
      sacrificed at the end of week 8, 12, 16 and 20 respectively. Group 8 animals
      constituted the controls and had equal volume of distilled water intramuscularly
      for 8 weeks. All sacrifices were by decapitation. The testes were carefully
      dissected out, their volumes measured, weighed and histological sections
      prepared. Morphometric assessment was carried out using the diameter, cross
      sectional area, number of profiles per unit area, numerical density and volume
      density of the seminiferous tubules and the relative and absolute volume of the
      seminiferous epithelium, stroma and lumen of tubules. RESULTS: The results showed
      that there was a general destruction of cells of the seminiferous tubules and the
      testicular interstitium that persisted even after the discontinuation of QU and
      to the end of our experiment that lasted 20 weeks. CONCLUSION: We conclude that
      QU has deleterious effect on the seminiferous tubules of Sprague-Dawley rats,
      though the mechanism of damage is unclear.

PMID- 16276695
TI  - Hepatitis B surface antigen (HbsAg) in blood and genital secretions of patients
      with sexually transmitted diseases in Ibadan, Nigeria.
AB  - A total of 100 patients attending the Special Treatment Clinic of the University
      Teaching Hospital (UCH), Ibadan between October, 1998 and April, 1999 were
      studied to detect Hepatitis B surface antigen (HbsAg) in the blood and genital
      discharges. This was with a view of establishing whether infected persons
      (positive by blood test) also excrete the antigen, HbsAg, in their genital
      secretions. Urethral swabs were collected from 63 male patients, while High
      Vaginal and Endocervical swabs were collected from 37 female patients. Blood
      samples were collected from all the patients. HbsAg was tested for by Enzyme
      immunoassay technique with Wellcozyme HbsAg kit. Of the 63 male patients, 10
      (15.9%) had HbsAg in the urethral secretion while 22 (34.9%) had it in their
      blood, 70% of these male patients were within the age range 11-30 years. Of the
      37 female patients, 34 (92%) had HbsAg in the Endocervical secretions, 6 (16.2%)
      of them had HbsAg in their blood. Eighty percent of the female patients with
      positive HbsAg in the genital secretions were within age range 21-40 years. This
      study documents that Hepatitis B virus can be transmitted sexually in this
      environment.

PMID- 16276696
TI  - Clinicopathological features and molecular markers of breast cancer in Jos,
      Nigeria.
AB  - BACKGROUND: Several studies have suggested that breast cancer in black women is
      associated with aggressive features and poor survival. This study examines
      molecular markers along with clinical stage and pathological grade in breast
      cancer material from Jos, Nigeria. STUDY DESIGN: The histological diagnoses of
      178 consecutive Nigerian patients with breast cancer were retrieved from their
      hospital records. A subset of 36 patients was staged and their tumours typed and
      graded. Immunohistochemical staining of sections from paraffin wax embedded
      tissues from these cases for the expression of oestrogen receptor (ER),
      progesterone receptor (PGR), Human ERBB2 (or HER2/neu), p53 and cyclin D1 (CCND1)
      was carried out using the avidin biotin complex (ABC) procedure. RESULTS: A
      majority of the cases were invasive ductal carcinoma (92.7%), high grade (grade
      3, 70.6%) and of late clinical stage (stages III and IV, 58.3%). Only 25% and
      27.8% of cases expressed ER and PGR respectively. The ERBB2 and CCND1 antigens
      were expressed in 25%, and 5.7% of cases respectively. The p53 protein was the
      most frequently expressed in this study (47.2% of cases). High grade tumours were
      significantly more likely to be ER and PGR negative (P = 0.006 and P = 0.002
      respectively). CONLCLUSION: There is predominance of high grade, invasive ductal
      carcinomas which are likely to be ER and PGR negative but p53 positive. These
      features suggest a biologically aggressive form of breast cancer in Nigerian
      women with the possibility of poor response to both hormonal therapy and
      chemotherapy.

PMID- 16276697
TI  - Correlates of self-reported physical health status of students of the University
      of Ibadan, Nigeria.
AB  - BACKGROUND: Young people including university students are a justifiable target
      for health status assessment as they form a large group that only recently
      escaped the adverse mortality experiences of childhood. This study was conducted
      in the University of Ibadan to determine the state and correlates of students'
      physical health. STUDY DESIGN: Seven hundred and fifty students were randomly
      selected from all eleven halls of residence by multi stage sampling.
      Questionnaires derived from the Duke Health Profile, a generic health instrument
      were administered by trained student peers and responses scored using the
      recommended guidelines. RESULTS: The overall response rate was 96.5%. The sample
      consisted of 484 males and 240 females; 602 undergraduate and 122 graduate
      students giving a male:female ratio of 2:1 and undergraduate:graduate student
      ratio of 5:1, similar to the ratio in the 18,690 strong general student body. All
      the university's faculties were represented. Most (92.3%) of the respondents were
      single. The group had a mean age of 23.8 years (SD 4.6). The mean physical health
      score was 7.9 (SD 1.67) out of a possible maximum of 10. High scores were
      significantly associated with male gender and frequent exercise. Sixteen students
      (2.2%) reported a physical handicap and 122 (16.3%) a medically diagnosed chronic
      illness. A mean of 1.14 days of disability occurred among the students in the
      month preceding the survey. Common causes of morbidity reported included fever
      (59.8%), nervousness (12.4%), cough (12.3%) and sleeping disorders (11.2%).
      CONCLUSION: The high mean physical health score recorded in this study indicates
      that students have an overall good level of functioning. However physical health
      status was associated with several lifestyle and personal factors.

PMID- 16276698
TI  - Vaginal flora of first time urban family planning attendants in Accra, Ghana.
AB  - OBJECTIVE: To determine the vaginal flora of first time urban Family Planning
      clients at Korle-Bu Teaching Hospital and to assess its implications for the
      contraceptive choices made. DESIGN: A cross sectional study. METHODS: A
      standardized questionnaire surveying the sociodemographic characteristics and the
      choice of Family Planning method was administered to 100 clients at the Korle Bu
      Teaching Hospital between March and September 2001. High vaginal and endocervical
      swabs were also taken during the inspection of the vagina and cervix using a
      sterile bivalve speculum. The specimens were transported in Amies transport
      medium to the Microbiology laboratory for processing. RESULTS: The age range of
      the clients was 19-48 years with a modal age of 28 years. Ninety-six percent of
      them were married while 86% lived in urban slums. Sixty-three percent were sure
      of their last menstrual period. Potential pathogens were isolated from culture in
      56% of the clients. Organisms causing bacterial vaginosis were the most prevalent
      in their genital tract. The intrauterine contraceptive device (IUCD) was the most
      common Family Planning method chosen, followed by the Norplant and the Depo
      Provera injections. Potential pathogens were isolated from culture in 50% of
      those who chose the IUCD. CONCLUSION: Potential pathogens were isolated from
      culture in 56% of these first-time clients and organisms causing bacterial
      vaginosis were the most prevalent in the genital tract. It is suggested that
      Family Planning clients who screened positive for potential pathogens and opt for
      the IUCD should be considered for prophylactic antibiotics at insertion.

PMID- 16276699
TI  - Attitudes of Nigerian dentists towards hepatitis B vaccination and use of barrier
      techniques.
AB  - OBJECTIVE: Hepatitis B virus constitutes a significant threat to the health of
      the dental professional. Infection with hepatitis B virus can however be
      prevented through hepatitis B vaccination and use of barrier techniques. This
      study therefore assesses the attitudes of Nigerian dentists towards hepatitis B
      vaccination and use of barrier techniques. MATERIALS AND METHOD: A questionnaire
      survey of 160 dental practitioners in Lagos, Ibadan, Ife and Benin. RESULT: 48.1%
      had complete vaccination, 3.1% incomplete vaccination and 48.8% no vaccination.
      97.5% reported routine use of gloves and 70.6% reported routine use of masks.
      61.3% and 23.1% reported routine use of protective gowns and eyewear
      respectively. CONCLUSION: There is need to improve the rate of hepatitis B
      vaccination among Nigerian dentists and to encourage consistent use of barrier
      techniques.

PMID- 16276700
TI  - Epidemiology of otitis media in a local tropical African population.
AB  - BACKGROUND: Otitis media is one of the most common childhood infections. There
      are however very few community based studies on the prevalence of this disease in
      Nigeria children. OBJECTIVES: To establish the community prevalence of otitis
      media: and to identify associated environmental and the host risk factors in
      Nigerian children. SETTING: A semi urban community of Ife Central Local
      Government area of Osun State, Southwestern part of Nigeria. MATERIAL AND
      METHODS: Thirty enumeration areas within the study location were randomly picked
      and their boundaries were defined with the assistance of the National Population
      Commission (NPC) Officials. Households were used as sampling units within the
      area. Children aged 1 day old-12 years in each selected household were
      identified. A questionnaire was administered to the mother/guardian of each
      child. Otoscopic examination, in addition to the general physical examination was
      carried out on each child. The data were analyzed using simple descriptive
      statistics, correlation and multivariate regression technique. RESULT: 600
      children aged 0-12 years were investigated. There were 299 males and 301 females.
      The prevalence of otitis media was found to be 14.7%. This comprises of acute
      otitis media (AOM) in 11.8%, chronic suppurative otitis media (CSOM) in 2.5%,
      while Otitis media with effusion (OME) was diagnosed in less than 1%. The peak
      age of incidence was found to be in the age group 1-4 years 55 (9.2%), while the
      least age of occurrence was found to be in the age group less than 1 year 10
      (1.7%). There was no statistical association between the duration of
      breastfeeding practice and occurrence of otitis media among the subject (P>0.05).
      There was no statistical association between the occurrence of otitis media and
      immunization (p>0.05). However there were 3 children who had otitis media
      associated with measles infection. A highly significant association was shown
      between exposure to household cooking fuel (wood smoke) and the occurrence of
      otitis media (P<0.05). Mother's educational status, number of children sleeping
      in the same room greater than four was found to demonstrate a strong association
      with the occurrence of Otitis media (p<0.05). CONCLUSION: Otitis media is
      prevalent among Nigeria children and it is found to occur more in children of
      mothers with lower educational status and in number of children greater than 4
      sleeping in the same room. A strong association was found between exposure to
      wood smoke in the living environment and the occurrence of otitis media.

PMID- 16276701
TI  - The daily water, sodium and potassium excretion in urine of Ghanaian children
      aged 5 to 12 years.
AB  - AIM: The aim of the study was to determine the daily losses of water, sodium and
      potassium in the urine of Ghanaian children who presented to the paediatric
      surgery unit of the Korle-Bu teaching hospital. METHODS: The urine of 74 Ghanaian
      children (51 male, 23 female) who presented to the Paediatric surgery unit of the
      Korle-Bu teaching hospital between June 1997 and January 1999 was collected over
      a 24 hour period and analysed to determine the volume, sodium and potassium
      content. RESULT: 74 children between the ages of 5 and 12 years with a mean age
      of 9 years were involved in the study. The mean daily urinary volume was 1136.8ml
      (95% confidence interval 1097.7 to 1176.0) with a range of 400 to 2400ml. The
      sodium excreted was 108.6mmol per day (confidence interval 105.3 to 111.9) with a
      range of 39.8 to 231.9mmol per day while the potassium excreted was 24.7mmol
      (confidence interval 23.7 to 25.7mmol) and a range of 6.25 to 69.9mmol per day.
      CONCLUSION: This study showed that children between 5 and 12 years in a ward lose
      a mean of 1136.8ml of water per day, 4.6mmol per kilogram of sodium per day, and
      1mmol per kg per day of potassium in their urine.

PMID- 16276702
TI  - Rigid bronchoscopic dilatation of postintubation tracheal stenosis.
AB  - BACKGROUND: Postintubation tracheal stenosis (PITS) occurs due to excessive
      pressure on the trachea by the cuff of the endotracheal tube which leads to local
      ischaemic necrosis of the tracheal cartilage and excessive growth of granulation
      tissue. The recognition of its aetiology and modifications in the design and
      management of endotracheal tubes have led to a diminished incidence of PITS. The
      management modalities that have been employed for the management of PITS include
      stenting, surgical resection and reconstruction, percutaneous dilatation, rigid
      bronchoscopic dilatation, fibreoptic assisted balloon dilatation and Nd:YAG
      (neodymium: yttritium-aluminum garnet) laser therapy with or without stenting.
      METHODS: Three female patients with a history of varying periods of endotracheal
      intubation after a period of acute respiratory failure who developed symptoms of
      tracheal stenosis 1-2 weeks post-extubationare presented. The mean age was 24 +/-
      12.49 years (range = 14-38 years). RESULTS: All the three patients were
      successfully managed by frequent, rigid bronchoscopy and gradual dilatation until
      the resolution of the tracheal stenosis and the return of pulmonary function
      tests (PFT) to normal. CONCLUSIONS: Rigid bronchoscopic dilation in patients with
      PITS provides safe, effective tracheal dilatation and improved pulmonary function
      in the medium term.

PMID- 16276703
TI  - Acute Otitis media, malaria and pyrexia in the under five age group.
AB  - BACKGROUND: Acute Otitis media is one of the most common childhood infections. It
      is responsible for every third visit to a pediatrician in a developed world.
      However, in Nigeria there is scanty knowledge about the incidence of Acute Otitis
      Media (AOM). OBJECTIVE: This study aimed at determining the incidence of AOM
      among under five year old children presenting with pyrexia, and to compare the
      incidence of AOM as a cause of pyrexia with the incidence of malaria in pyrexic
      children. DESIGN: It is a cohort study of 200 children of between the ages of 2
      weeks and five years with a rectal temperature of 38 degrees C and above, seen
      over a period of 3 months. SETTING: The study was conducted at the Obafemi
      Awolowo University Teaching Hospital (OAUTHC) Comprehensive Health Centre,
      Eleiyele, and the children emergency room of the OAUTHC, Ile-Ife. PATIENTS AND
      METHODS: A questionnaire to collect information on the demographic data was
      administered to each mother/guardian of the patient. Otoscopic examination using
      a battery-operated hand held otoscope and magnifying lenses were done in addition
      to general systemic physical examination. Thin and thick blood smears were made
      for malaria parasite. The dried slides were examined under the microscope using
      the X 100 objective. Sixteen of the patients' slides were lost after processing.
      RESULTS: Out of the 200 patients that were studied, 58 (29%) had AOM. The highest
      incidence was recorded in the age group 12-24 months while the least age of
      occurrence was found to be the age group 4-5 years. Malaria parasitemia was found
      in 81 (43.5%) while 21 (25.9%) of those with parasitemia also had AOM. But 76
      (36%) of the study population had neither AOM nor malaria parasitemia.
      CONCLUSION: Acute Otitis media was found in 29% of under five years old
      presenting with pyrexia. It was found to be highest in the first and second year
      of life, and was found to be least in the 5th year of life. Malaria was found in
      81 (43.5%) of the children, and 21 (10.5%) of the children had malaria with a co
      existing AOM.

PMID- 16276704
TI  - An audit of peptic ulcer surgery in Ibadan, Nigeria.
AB  - BACKGROUND: Several operations are useful for peptic ulcer surgery, these include
      Vagotomy and pyloroplasty, Vagotomy and antrectomy, Vagotomy and
      gastrojejunostomy, and Highly Selective Vagotomy to name a few. Utilising any of
      these procedures may be due to the operator's preference or more importantly the
      suitability of the operation to the individual patient. This study was carried
      out to see the surgical presentation of chronic peptic ulcer disease patients and
      the form of ulcer-surgery utilised in the University College Hospital Ibadan,
      Nigeria. STUDY DESIGN: A retrospective study of all the patients who were
      operated on for complications of peptic ulcer disease between January 1990 and
      December 2003 at the above-mentioned institution by studying the case-files, ward
      admission records and operation room registers of such patients. RESULT: There
      were 122 patients, 90 male and 32 female with a Male:Female ratio of 3:1. Pyloric
      stenosis accounted for 56.6% of patients followed by perforation (29.5%),
      bleeding (9.8%) and gastric ulcer (4.1%). Yearly presentations seem to be
      reducing. Truncal vagotomy and drainage was performed in 78.64% of the patients,
      simple closure for perforation in 29.5%, partial gastrectomy for 4.1% while the
      remaining 2.4% had underunning of a bleeding vessel. CONCLUSION: Pyloric stenosis
      (also called gastric outlet obstruction) is the most common surgical presentation
      of peptic ulcer disease in the University College Hospital Ibadan and Truncal
      Vagotomy and drainage is the most common surgical procedure performed for peptic
      ulcer.

PMID- 16276705
TI  - Efficacy of nebulized furosemide in children with moderate attack of asthma.
AB  - BACKGROUND: Bronchodilators are the most commonly used drugs for asthma. However,
      alternative treatment is necessary for those patients who experience adverse
      effects from bronchodilators. OBJECTIVE: To investigate the efficacy of nebulized
      furosemide in children with moderate asthma exacerbations. METHOD AND MATERIALS:
      A double-blind randomized, controlled trial involving three groups of children
      with moderate attack of asthma. Twenty children were enrolled in group A and
      received nebulized albuterol, 20 children in group B received nebulized
      furosemide and 19 children in group C received both albuterol and furosemide.
      Pulmonary function parameters, peak flow rates, respiratory rate, oxygen
      saturation and clinical scores were obtained before and after treatment. RESULTS:
      The maximum increases in FEV1 achieved were 21.1 +/- 4.6 %, 20.8 +/- 3.2 and 21.7
      +/- 4.9 in groups A, B and C respectively. The differences between the groups
      were not significant. Maximum increase in FVC was 20.3 +/- 1.6, 22.5 +/- 5.8 %
      and 24.5 +/- 4.9 % in groups B and C respectively. The difference between the
      three groups was not statistically significant. With regards to peak expiratory
      flow rate (PEFR), the mean increase after treatment was 23.5 +/- 8.6% and 21.8 +/
      6.3% in groups A and B respectively. There was significant increase in PEFR in
      group C children (26.0 +/- 9.1%; p = 0.01). There was no statistical significant
      difference among the three groups regarding the improvement in respiratory rate,
      SaO2 and clinical scores. CONCLUSION: Combination of both furosemide and
      albuterol led to significant increase in peak flow rate but it did not
      significantly affect FEV1, FVC, FEF 25-75, respiratory rate, SaO2 or clinical
      scores as compared to other groups. There were no significant adverse effects
      from the three drugs used.

PMID- 16276706
TI  - An audit of excised breast lumps in Ghanaian women.
AB  - BACKGROUND: In our environment, all patients presenting with breast masses insist
      on complete surgical removal as the preferred treatment option acceptable to
      them. We report on a 6-year prospective study of the clinical and pathological
      features of these breasts masses excised for histopathological examination. STUDY
      DESIGN: Details of all consecutive women referred to the surgical out-patients'
      clinic of the Komfo Anokye Teaching Hospital from January 1998 to December 2003
      inclusive, for clinical assessment and excision of breast masses were
      prospectively recorded. Open surgical biopsies were performed on these masses and
      the pathological features recorded. RESULT: A total of 443 patients were
      reported. Approximately 80% of the women were 40 years old or younger There were
      355 (80.9%) benign breast lesions and 88 (19.1%) carcinomas. The principal
      histopathological types were fibroadenoma, fibrocystic breast changes and
      carcinoma occurring in 47.7%, 23.9% and 19.1% of the patients respectively. The
      cumulative frequency at >30 years for fibroadenoma and carcinoma was 0.81 and
      0.11 respectively. No carcinomas were found below 26 years. There was a
      significant association between the ages of the patients and the type of breast
      disease (X2 = 20.9 P <0.05). CONCLUSION: Discrete breast masses in Ghanaian women
      are mostly due to benign breast disease. The risk of cancer increases with the
      age of the patient especially after 30 years.

PMID- 16276707
TI  - Health problems of mill operators in a tropical African population.
AB  - The study reports a questionnaire based survey on mill operators in a large
      market in Ibadan, Southwest Nigeria. One hundred and twenty respondents, 65 males
      and 55 females aged between 18 and 65 years were interviewed and noise
      measurements were done at various work stations. Health problems reported by
      these workers include headaches 73%, backache 53% and respiratory symptoms such
      as cough 37% rhinitis 63% and wheezing 13%. Thirty four respondents (28%)
      reported a difficulty in hearing mostly due to tinnitus. Four complained of
      deafness. Twenty-three (19%) had raised blood pressure of 140/90Hg and above. In
      spite of the high levels of dust in the work environment only 15 (13%) of workers
      used a face cloth to cover their noses. Noise levels at the work stations ranged
      from 88-90dB from smaller machines and 101-105 dB for larger machines. None of
      the workers used hearing protection in any form. Health education of workers and
      the provision of low cost protective equipment may alleviate the suffering of
      these workers.

PMID- 16276708
TI  - Caring for individuals with dementia: the Nigerian experience.
AB  - Recent epidemiological data, mainly from cross-cultural studies, have revealed
      that the burden of dementia and Alzheimer's disease (AD) the most common type, is
      significantly lower in developing than in the industrialized countries. Caring
      for individuals with dementia is a major consideration because most developing
      countries do not have the resources to provide comprehensive care in
      institutions. Home care that is practiced is ideal given the cultural scenario
      especially with the extended family support. Public policies on the care of the
      elderly however need to be well articulated and implemented. Hypertension was the
      most frequent medical co-morbidity of the demented subjects and about a third of
      subjects with AD were hypertensive, which may support vascular hypothesis in AD
      pathogenesis. The important behavioural disturbances experienced by caregivers
      and the associated stress levels were highlighted. The model used on the
      Indianapolis-Ibadan Dementia Study which involves periodic home visits, and
      empowerment of caregivers through regular meetings is envisaged to make caring
      for these individuals easier and adaptable in other African communities.

PMID- 16276710
TI  - Recurrent bilateral fronto-ethmoidal mucocoele with intracranial extension: a
      case report.
AB  - Mucocoeles of the paranasal sinuses are relatively uncommon and rarely bilateral,
      the frontal and ethmoidal sinuses being most commonly affected. Rarely, fronto
      ethmoidal mucocoeles expand and extend into the anterior cranial fossa producing
      mass effect. We report a 66-year-old woman, who presented with a 20-year history
      of recurrent bilateral progressive proptosis and supra orbital swellings with
      blindness in the left eye. Ultrasound scan of the left eye showed a large cystic
      mass in the orbit due to extension of ipsilateral frontal mucocoele. Computed
      tomographic brain scan showed large bilateral fronto-ethmoidal mucocoeles,
      erosion of the right orbital roof, right posterior and left anterior sinus walls,
      and extension of the right frontal sinus into the anterior cranial fossa with
      mass effect. The patient had a bicoronal craniotomy and bilateral fronto
      ethmoidectomy with direct drainage of independent right mucocoele and left
      mucopyocoele. This case illustrates complications that may result from chronicity
      and treatment failure in patients with sinus mucocoeles.

PMID- 16276709
TI  - The efficacy and toleration of celecoxib (Celebrex) in the treatment of
      osteoarthritis in Nigeria: a multicentre study.
AB  - BACKGROUND: Non-selective, non-steroidal anti-inflammatory drugs (NSAIDs) are
      effective in terms of pain relief and improving function in osteoarthritis. The
      advent of cyclooxygenase-2 (Cox-2) specific inhibitor, celecoxib, in the
      treatment of osteoarthritis has shown similar efficacy in relieving pain in
      osteoarthritis with low incidence of GI (Gastrointestinal) symptoms. OBJECTIVE:
      To determine the efficacy and toleration of celecoxib in treatment of
      osteoarthritis in Nigerian population. METHODS: Eighty patients were recruited
      from six tertiary health institutions scattered over Nigeria. A fixed dose of 200
      mg celecoxib was administered daily with patient seen on the second and six weeks
      after commencement of study. Efficacy of the drug and safety were assessed during
      the study. RESULTS: The patients had a mean age of 57.8 years with a standard
      deviation of 13.3 year. The mean weight was 74.7 +/- 14.9kg while the female sex
      constituted the majority (73.8%) of the patients. Using the physician global
      assessment of osteoarthritis instrument, 36.3% of the patients were rated as
      having poor arthritis score at baseline. This value reduced to 2.6% at second
      visit and 0.00% at end of the study respectively. There was no significant
      difference between the vital signs, haematological indices, renal and hepatic
      function at baseline and the final visit. There was no case of serious adverse
      effect. CONCLUSION: The study showed statistically significant improvements in
      the symptoms of osteoarthristis following the administration of Celecoxib 200mg
      daily for six weeks.

PMID- 16276711
TI  - Bilateral traumatic anterior hip dislocation--a case report.
AB  - We report a 33-year-old trader with bilateral traumatic anterior hip dislocation
      following a road traffic accident. Both hip dislocations were reduced under
      general anesthesia followed by immobilization of the hips with skin traction. He
      discharged himself against medical advice one week after injury.

PMID- 16276712
TI  - Unusual presentation of thyrotoxicosis--a case report and review of literature.
AB  - BACKGROUND: The majority of patients with thyrotoxicosis are readily diagnosed
      clinically. It must be accepted however that not every patient presents with the
      characteristic picture. Thyrotoxicosis occasionally presents in an unknown or
      atypical fashion in which the diagnosis may not be obvious. CASE REPORT: A 45
      year-old woman presented with choreoathetoid movements of the right upper limb,
      persistent vomiting and generalized body weakness. Over the next few weeks, the
      clinical picture slowly evolved to give the characteristic symptoms and signs of
      thyrotoxicosis, which were not evident at presentation. Thyroid function tests
      revealed elevated serum thyroxine and triiodothyronine as well as low thyroid
      stimulating hormone concentrations, confirming the diagnosis of thyrotoxicosis.
      CONCLUSION: This case illustrates unusual initial presenting features of
      thyrotoxicosis, which long preceded the development of the characteristic and
      more common manifestations. This led to a delay in the diagnosis. Awareness of
      these atypical presentations will further assist the physician to make a timely
      and cost effective diagnosis of this condition.

PMID- 16276713
TI  - Acute coronary syndrome caused by anomalous origin of the right coronary artery
      from the left sinus of Valsalva.
AB  - An anomalous origin of right coronary artery from the left sinus of Valsalva is a
      rare congenital anomaly of the coronary arteries. We describe a 40-year-old male
      hypertensive and hyperlipidemic patient who presented with typical anginal pain
      with normal ECG and echocardiogram and abnormal exercise ECG Test Coronary
      angiography showed an anomalous origin of the right coronary artery from the left
      sinus of Valsalva, an anomaly that has been associated with angina, myocardial
      infarction and sudden cardiac death. The clinical profile of this congenital
      anomaly is also reviewed.

PMID- 16276715
TI  - Patients first.

PMID- 16276714
TI  - Generalised Burkitt's lymphoma involving both breasts--a case report.
AB  - BACKGROUND: Burkitt's lymphoma is a disease of children age ranging 8-10 years.
      Lymphoma involving the breast is an unusual clinical entity, which is rarely
      distinguished preoperatively from other more common forms of breast cancer. The
      Management differs from the more typical adenocarcinoma of the breast in that the
      emphasis is on systemic therapy. CASE: We report a 27-year-old pregnant Nigerian
      civil servant at 28 weeks gestation, who presented with multiple organ swellings
      including both breasts. She was diagnosed histologically as primary breast
      Burkitt's lymphoma. She was treated with systemic chemotherapy after spontaneous
      abortion. She had a recurrence of the lesion in the right breast a month later
      that was excised. Presently there is no evidence of any mass. CONCLUSION:
      Compared with breast carcinoma, primary breast lymphoma is a rare disease but
      should be considered in the differential diagnosis of breast masses.

PMID- 16276716
TI  - Telemedicine and e-health.

PMID- 16276717
TI  - Handling disruptive patients.

PMID- 16276718
TI  - ePractice: the future is now.

PMID- 16276719
TI  - Loss prevention case of the month. Critical review.

PMID- 16276720
TI  - The magnitude of the meth epidemic.

PMID- 16276721
TI  - How to choose a financial advisor for effective asset & investment management.

PMID- 16276722
TI  - Asset protection for your practice through ASSN. Group plan.

PMID- 16276723
TI  - Pelvic hematoma following placement of Transobturator Tape.

PMID- 16276724
TI  - Isn't it about time for better health.

PMID- 16276725
TI  - Integrating medicine and psychiatry: Psychiatric Medical Units (PMUs).

PMID- 16276728
TI  - [Adverse effects].

PMID- 16276727
TI  - [Surgical extraction techniques for companion animals].
AB  - The extraction of teeth in cats and dogs is a common surgical intervention in
      veterinary practice. This article describes the correct technical approach to the
      surgical extraction of dental elements, focussing on the indications, possible
      complications, and advantages of this technique.

PMID- 16276729
TI  - [New method to weaken the parasite for vaccine development].

PMID- 16276730
TI  - [Neurologic form of rhinopneumonia].

PMID- 16276731
TI  - [Mandatory identification of horses in Belgium].

PMID- 16276732
TI  - [Fluffy or baked smell?].

PMID- 16276733
TI  - [Veterinary congress in Macedonia. New member states are getting help with
      implementation of EU-laws].

PMID- 16276734
TI  - [Recognition od Dutch 'Campylobacter' laboratory by OIE].

PMID- 16276735
TI  - [Observing BVD infection].

PMID- 16276736
TI  - [Fees for sentinel surveillance. How are they determined?].

PMID- 16276737
TI  - [Dad, the rabbits have grown up!].

PMID- 16276738
TI  - [Two cases of Bartholin's gland abscesses caused by Streptococcus pneumoniae and
      Haemophilus influenzae].
AB  - Most of Bartholin's gland abscesses have been thought to be caused by
      microorganisms found in opportunistic infections. However, we have encountered
      two very interesting cases of Bartholin's gland abscesses caused by Streptococcus
      pneumoniae and Haemophilus influenzae, two major pathogens of respiratory tract
      infections. In the first case, since abscess formation was not observed due to
      disintegration, cefdinir (CFDN), 300 mg/day, t.i.d. for 5 days was administered.
      The treatment improved clinical symptoms, but relapse occurred 3 days after the
      administration was discontinued. Microbiological examination of pus revealed the
      presence of Streptococcus pneumoniae and Finegoldia magna, and it also showed
      that the isolated S. pneumoniae was penicillin-resistant S. pneumoniae (PRSP).
      After an incision and drainage of abscess, cefteram pivoxil (CFTM-PI), 300 mg/day
      t.i.d. for 7 days, was administered, and the cure was confirmed. In the second
      case, after an incision and drainage of Bartholin's gland abscess, amoxicillin
      (AMPC), 750 mg/day, t.i.d. for 5 days, was administered. The treatment improved
      clinical symptoms temporarily. However, the symptoms deteriorated 7 days after
      the operation, and the patient was diagnosed with relapse. Microbiological
      examination of pus revealed the presence of Haemophilus influenzae and
      Peptostreptococcus anaerobius, and it also showed that the isolated H. influenzae
      was beta-lactamase-nonproducing ampicillin-resistant H. influenzae (BLNAR). After
      performing additional incision and drainage of abscess again, CFTM-PI, 300
      mg/day, t.i.d. for 7 days, was administered, and the cure was confirmed. In
      addition, the analysis of these two cases using PK/PD theory revealed that the
      time above MIC reached 100% with administration of CFTM-PI 300mg, t.i.d.
      suggesting that the dosage is sufficient for treating these infections. There are
      other cases of external genitalia infections caused by microorganisms usually
      associated with respiratory tract infections like cases that we are reporting
      here. Therefore, it is necessary to consider a possible infection by drug
      resistant bacteria even for a case of external genitalia infection. In addition,
      it was thought that adjusting dosage and method for administration of
      antibacterial agents based on PK/PD theory would help to rovide efficient
      treatment.

PMID- 16276739
TI  - [Clinical analysis of antibiotic treatment for febrile neutropenia].
AB  - Patients with hematological malignancies and aplastic anemia become complicated
      by critical infections, which are one of the common causes of death in many
      cases. This is a retrospective investigation of the factors that affect the
      efficacy of antibiotic treatment of febrile neutropenia (FN). The subjects
      consisted of 98 cases that developed FN during their hospitalization in this
      department and received antibiotics as a first-line treatment. Parameters
      evaluated were age, gender, with or without administration of granulocyte-colony
      stimulating factor (G-CSF), with or without hematopoietic transplantation, the
      number of antibiotics, the type of antibiotics, the highest level of C-reactive
      protein (CRP), with or without antifungal prophylaxis, the duration of
      neutropenia, and the number of neutrophils before and after the administration of
      antibiotics. Logistic analysis was used for statistical evaluation. With
      univariate analysis, significant clinical efficacy was observed with the use of
      carbapenems (p = 0.0009, Odds; 4.58) when the number of neutrophils was not less
      than 500/microL (P < 0.0001, Odds: 14.1) after administration of antibiotics.
      Furthermore, even when multivariate analysis was performed, significant clinical
      efficacy was observed independently in the use of carbapenems (P = 0.02, Odds:
      3.73) and when the number of neutrophils was not less than 500/microL (P <
      0.0001, Odds: 10.4) after administration of antibiotics. In this investigation,
      as a first-line treatment of FN, carbapenem antibiotic is recommended as a
      primary choice, when the number of neutrophils was expected to decrease after
      administration.

PMID- 16276741
TI  - New voice emerging. Nascent think tank may have trouble being heard.

PMID- 16276740
TI  - Changing the balance. In ordering Evanston Northwestern to divest a hospital, the
      FTC could give insurers more power in negotiating with providers.
AB  - As officials at Evanston Northwestern Healthcare plan their appeal of an order to
      divest one of its three hospitals, hospitals around the country ponder the
      national implications of the ruling. Industry observers say the action means
      hospitals may have a harder time merging to gain leverage with insurers. The
      AHA's Melinda Hatton, right, says she was "deeply disappointed" but not surprised
      by the ruling.

PMID- 16276742
TI  - Data dispute continues. Hospital groups question JCAHO's use of information.

PMID- 16276743
TI  - Few deposits. Feds fail to report malpractice cases to databank.

PMID- 16276744
TI  - Seeking more disclosure. Proposed 990 Form would ask about loans, conflicts.

PMID- 16276746
TI  - One way to ease budget cuts. Give fraud fighters enough resources to catch health
      program thieves.

PMID- 16276745
TI  - Applying the brakes. UAW deal to affect providers as well as workers.

PMID- 16276747
TI  - Get certified. Medical practice administrators need to master a core body of
      knowledge.

PMID- 16276748
TI  - A bigger brood. As OB/GYN practices grow nationwide, what's good news for the
      docs can be bad news for hospitals and health plans.

PMID- 16276749
TI  - Firefighter to fraudfighter. HHS' new inspector general brings decades of
      government experience, legal scholarship.

PMID- 16276750
TI  - Championing local cancer care. Kurt Tauer honored for his leadership of Community
      Oncology Alliance.

PMID- 16276751
TI  - What does brain imaging tell us about the predisposition to suicidal behavior.

PMID- 16276752
TI  - Suicide in developing countries (1): frequency, distribution, and association
      with socioeconomic indicators.
AB  - OBJECTIVE: Suicide is a global public health problem, but relatively little
      epidemiological investigation of the phenomenon has occurred in developing
      countries. This paper aims to (1) examine the availability of rate data in
      developing countries, (2) provide a description of the frequency and distribution
      of suicide in those countries for which data are available, and (3) explore the
      relationship between country-level socioeconomic factors and suicide rates. It is
      accompanied by two companion papers that consider risk factors and preventive
      efforts associated with suicide in developing countries, respectively. METHOD:
      Using World Health Organization data, we calculated the average annual male,
      female, and total suicide rates during the 1990s for individual countries and
      regions (classified according to the Human Development Index [HDI]), and examined
      the association between a range of socioeconomic indicators and suicide rates.
      RESULTS: For reasons of data availability, we concentrated on medium HDI
      countries. Suicide rates in these countries were variable. They were generally
      comparable with those in high HDI countries from the same region, with some
      exceptions. High education levels, high telephone density, and high per capita
      levels of cigarette consumption were associated with high suicide rates; high
      levels of inequality were associated with low suicide rates. CONCLUSION:
      Epidemiological investigations of this kind have the potential to inform suicide
      prevention efforts in developing countries, and should be encouraged.

PMID- 16276753
TI  - Suicide in developing countries (2): risk factors.
AB  - The majority of studies on risk factors for suicide have been conducted in
      developed countries, and less work has been done to systematically profile risk
      factors in developing countries. The current paper presents a selective review of
      sociodemographic, clinical, and environmental/situational risk factors in
      developing countries. Taken together, the evidence suggests that the profiles of
      risk factors in developing countries demonstrate some differences from those in
      developed countries. In some developing countries, at least, being female, living
      in a rural area, and holding religious beliefs that sanction suicide may be of
      more relevance to suicide risk than these factors are in developed countries.
      Conversely, being single or having a history of mental illness may be of less
      relevance. Risk factors that appear to be universal include youth or old age, low
      socioeconomic standing, substance use, and previous suicide attempts. Recent
      stressful life events play a role in both developing and developed countries,
      although their nature may differ (e.g., social change may have more of an
      influence in the former). Likewise, access to means heightens risk in both, but
      the specific means may vary (e.g., access to pesticides is of more relevance in
      developing countries). These findings have clear implications for suicide
      prevention, suggesting that preventive efforts that have shown promise in
      developed countries may need to be tailored differently to address the risk
      factor profile of developing countries.

PMID- 16276754
TI  - Suicide in developing countries (3): prevention efforts.
AB  - Until now, suicide prevention efforts have been limited in developing countries,
      although there are pockets of excellent achievement. Various universal,
      selective, and indicated interventions have been implemented, many of which
      target a different pattern of risk factors to those in developed countries. In
      the absence of sufficient mental health services, developing countries rely
      heavily on nongovernment organizations (NGOs) to provide crisis interventions for
      suicidal individuals, as well as proactive interventions aimed at raising
      community awareness and building resilience. Often these NGOs work within a
      social and public health framework, collaborating with others to provide nested
      suicide prevention programs that are responsive to local community needs. There
      is a clear need to develop appropriate, relevant and effective national suicide
      prevention plans in developing countries, since, to date, only Sri Lanka has done
      so. These plans should focus on a range of priority areas, specify the actions
      necessary to achieve positive change in these priority areas, consider the range
      of collaborators required to implement these actions, and structure their efforts
      at national, regional, and local levels. The plans should also promote the
      collection of accurate data on completed and attempted suicide, and should foster
      evaluation efforts.

PMID- 16276755
TI  - Suicidal ideation in Pakistani college students.
AB  - Suicidal behavior includes ideation, attempts and completed suicides. Information
      on suicidal behavior from Pakistan, a conservative South Asian Islamic country,
      is lacking. To address the issue, a pilot study was carried out to assess the
      prevalence of suicidal ideation in Pakistani college students. Suicidal ideation
      was assessed on the basis of responses to four questions contained in the
      depression subscale of the General Health Questionnaire-28. Of the total 217
      completed questionnaires, the overall rate of suicidal ideation was 31.4%. While
      there was no significant difference between genders, more females (33%) than
      males (29.2%) responded positively. Respondents belonging to single parent
      families and those living at home, compared to those using hostel facilities,
      reported higher rates. The reported rate in our sample is higher than similar
      studies conducted elsewhere. There is the need for more information in this
      important area of suicidal behavior, including studying such feelings in school
      going children as well as in a larger community sample. The findings of such
      studies can contribute to our understanding of the suicidal process in the
      Pakistani population and to address it at various levels.

PMID- 16276756
TI  - Suicide prevention: a pragmatic review of recent studies.
AB  - Because of the almost complete absence of randomized controlled trials
      demonstrating the effectiveness of specific treatments, there is sometimes a
      degree of pessimism about our ability to prevent suicidal behaviors. However, the
      methodological challenges to produce such research are formidable and may never
      be overcome. Therefore, a pragmatic review of evidence-based methods of suicide
      prevention is required. This review of recent studies using a variety of research
      strategies, both nonpharmacological and pharmacological, particularly at the
      community level, provides persuasive data that suicide prevention is possible.
      This is achievable by the application of broad community and professional
      education programs, as well as by the optimum management of mental disorders.

PMID- 16276757
TI  - Toward an understanding of suicide in First-Nation Canadians.
AB  - Despite having a suicide rate that is consistently higher than the national
      Canadian average, our understanding of suicide within First-Nation Canadians is
      limited. Furthermore, our historical research endeavors in this area have tended
      to focus on clarifying characteristic symptoms, symptom clusters, and risk
      factors; establishing causal links; and identifying clinical phenomena associated
      with the presence of increased risk and have tended to use quantitative methods.
      The "voice" of the suicidal First-Nation person is largely "silent" within this
      literature and, as a result, any understanding we have of this issue is
      unbalanced and incomplete. Accordingly, this paper makes the case for adding a
      complementary (or shifting the existing) research emphasis for studying suicide
      within First-Nation Canadian communities. It suggests a complimentary strategic
      research activity that is more concerned with qualitative methods: A model that
      augments the current understanding of the "developmental-existential" model of
      suicide by accessing and articulating the "voices" of the First-Nation people
      themselves.

PMID- 16276758
TI  - Juvenile suicide in confinement in the United States results from a national
      survey.
AB  - The first national study of juvenile suicide in confinement in the United States
      determined the extent and distribution of juvenile suicides (in juvenile
      detention centers, reception centers, and training schools); as well as gathered
      descriptive data on demographic characteristics of each victim, characteristics
      of the incident, and characteristics of the juvenile facility which sustained the
      suicide. Significant findings were found in the areas of time and location of the
      deaths, as well as adequacy of suicide prevention measures in facilities
      sustaining the deaths.

PMID- 16276759
TI  - The Farberow Award: the man.

PMID- 16276760
TI  - [CME radiology 10. Routine thoracic image, hypercalcemia].

PMID- 16276761
TI  - [ECG diagnosis. What is your diagnosis?].

PMID- 16276762
TI  - [Complications of chronic inflammatory bowel disorders: treatment].
AB  - Complications of chronic inflammatory bowel disease are nowadays relatively rare
      due to improved surgical and conservative treatment. They are better recognized
      with modern diagnostic techniques and can be more easily classified and thus
      treated. Analyses of large cohorts demonstrate that the survival of patients is
      still not completely normal. However, only a small part of the deaths observed is
      due to inflammatory bowel disease. For the various complications such as toxic
      megacolon, severe bleeding, stenosis and ileus, fistulae and abscesses well
      defined therapeutic approaches are available in spite of the lack of larger
      controlled trials. Knowledge of these approaches by the primarily treating
      physician is necessary in order to provide patients with adequate treatment from
      competent experts. Regarding neoplasia earlier numbers are probably not valid any
      more since consequent remission maintenance treatment and observation seems to
      eliminate this complication to a large extent.

PMID- 16276763
TI  - [Surgical therapy of complicated inflammatory bowel disease].
AB  - The etiology of chronic inflammatoric bowel disease is unknown, conservative
      treatment will be reduced to the management of immunologic and inflammatoric
      reaction. The large majority of patients affected with Crohn's disease and also
      nearly 50% of patients with ulcerous colitis require surgery during their
      clinical history. The indication for surgery is a balance between the severity
      and the complications of the disease and the potential disadvantages of surgery.
      For surgical therapy the differentiation of Crohn's disease and ulcerous colitis
      is essential because of the differentiated character of both diseases. In Crohn's
      disease surgical therapy will be performed by the management of Crohn's specific
      complications like stenosis, fistula, and abscess by bowel preserveration.
      Limited resection and/or strictureplasty do not influence morbidity and rate and
      also time of recurrence. Ulcerous colitis can be cured when the colorectal mucosa
      will be removed totally by radical surgery, i.e. restorative proctocolectomy. The
      satisfactory outcome in 70 to 90% of patients with a cumulative failure rate of
      10 to 15% over a 10-year-period improves the quality of life.

PMID- 16276765
TI  - [CME-ECG 8. Palpitations after fall from Velo].

PMID- 16276764
TI  - [Prevention and early detection of colorectal cancer].
AB  - With 60000 new cases and approximately 31000 deaths annually the colorectal
      carcinoma is the second most frequent cause of death due to a tumour in Germany.
      In over 90% of all colorectal carcinomas the precursors (adenomas) are well
      known. Moreover the early carcinoma of the colorectum (pT1-carcinoma) has an
      exceptional benign prognosis. To detect those precursors and early stages
      effective methods of primary, secondary and tertiary prevention are available.

PMID- 16276766
TI  - [Training arrangement for military doctor's assistants. (Communication 2)].
AB  - Since 1999 the military medical attendants' training was organized in Tomsk
      Military Medical Institute. In 2002 the first graduation of medical service
      lieutenants took place. Resumption of training of military medical specialists
      with secondary education required solving the complex of organisational,
      educational--and methodological and other problems. Previously the medical
      service didn't face with these problems.

PMID- 16276767
TI  - [Surgical care rendered to the wounded during the antiterrorist operations in the
      Northern Caucasus in the distant medical battalions of divisions. (Communication
      3)].
AB  - Broad usage of helicopters for an evacuation of wounded from the battle orders
      and forward aid station directly to Multiprophyle Military Hospitals of 1-st
      level during armed conflicts on Northern Caucasus has essentially changed the
      purposes and nature of a medical care to wounded in Separate Medical Battalions
      (SMB) of divisions. The primary goal of SMB became valuable preparedness of
      wounded to an evacuation from the battle orders of a division, that was reached
      by moving out of the surgeons and anesthesiologists to regimental aid station and
      medical companies. For adding up during armed conflicts on Northern Caucasus of
      medico tactical conditions it was justified: 73% wounded, admitted in SMB with
      damages of minimal and mean severity and not required emergency operations, after
      rendering them of initial physician care were evacuated by helicopters to
      Multiprophyle Military Hospitals of 1-st level. The analysis of experience of
      three SMB in Armed conflict 1999-2002 has shown, that the measures of initial
      surgical care should appear only for saving life of injured under the specially
      designed indications and with observance of a number of the relevant technical
      features, directional on acceleration and decreasing of surgical operations
      severity.

PMID- 16276768
TI  - [Morphofunctional characteristics of intestinal urinary reservoir].

PMID- 16276770
TI  - [Effect of cyclic hypoxia-hypercapnia on microcirculatory blood flow in healthy
      servicemen].
AB  - To evaluate how the training on hypoxia-hypercapnia combined effect (HHCE)
      influences the microcirculatory state 25 healthy servicemen were examined who
      underwent 20-day HHCE cycles--30-minute breathing, O2 - 12%, CO2 - 4%. It was
      established that during HHCE compared with atmospheric aie breathing the
      microcirculatory blood flow increases on the average by 35%. During training the
      microcirculatory reactivity in response to HHCE progressively increases. The
      gradual intensification of microcirculation in normal breathing conditions was
      noted.

PMID- 16276769
TI  - [Hemorrhagic fever with renal syndrome among servicemen in Primorskii Region of
      Russia].
AB  - The data about the incidence of hemorrhagic fever with renal syndrome (HFRS)
      among the servicemen stationed in HFRS endemic territories at Primorye Region are
      presented. The authors have shown the epidemiological significance of outbreaks,
      group and sporadic cases of HFRS especially in servicemen aged 18-20. During the
      outbreaks the maximal HFRS incidence is registered during 2 weeks after the first
      case. 104 HFRS cases were registered in the servicemen. Among them 77.8 +/- 3.0%
      were at the age of 18-20; 7.4 +/- 2.9% of these cases were lethal.

PMID- 16276771
TI  - [The history of discussion about the subordination of Military Sanitary
      Headquarters to the Workers' and Peasants' Red Army: Health National Commissariat
      or Navy National Commissariat?].

PMID- 16276772
TI  - [Vasilii Ivanovich Priselkov (the work experience of the field military medical
      inspector in the theatre of war operations in Bulgaria in 1877-1878)].

PMID- 16276773
TI  - [Karl Zeiidlits--the military physician, professor of Imperial Medical Surgical
      Academy].

PMID- 16276774
TI  - [S. B. Gatagov--the prominent organizer of military health care].

PMID- 16276775
TI  - [Deed in the name of life].

PMID- 16276776
TI  - [Training and retraining of military medical cadres during the years of Great
      Patriotic war].

PMID- 16276777
TI  - [The Department of Military and Extreme Medicine in the Samara State Medical
      University is 75 years].

PMID- 16276778
TI  - Hydride-based silica stationary phases for HPLC: fundamental properties and
      applications.
AB  - Silica hydride is a recent development in chromatographic support materials for
      HPLC where hydride groups replace 95% of the silanols on the surface. This
      conversion changes many of the fundamental properties of the material as well as
      the bonded stationary phases that are the result of further chemical modification
      of the hydride surface. The general approach for fabricating the silica hydride
      and subsequent bonded phases is reviewed. Properties of the silica hydride
      surface are compared to those of the standard material obtained in the
      preparation of most commercial HPLC stationary phases. Some unique
      chromatographic properties of hydride-based phases are described as well as some
      general application areas where these bonded materials may be used in preference
      to or have advantages not available from typical stationary phases.

PMID- 16276779
TI  - Methacrylate-based chromatographic media.
AB  - This review summarizes the preparation and application of chromatographic
      separation media based on methacrylate monomers with a major focus on highly
      crosslinked macroporous beads prepared from 2-hydroxyethyl methacrylate and
      glycidyl methacrylate, respectively. The effects of process variables such as
      composition of the polymerization mixture that includes monomers, porogenic
      solvents, and free radical initiator, suspension stabilizer, reaction
      temperature, and stirring are detailed for both classical and templated
      suspension polymerization. In addition, specific features of the preparation of
      monodisperse beads are also discussed. The performance of methacrylate-based
      separation media is demonstrated on numerous separations in a variety of
      chromatographic modes.

PMID- 16276780
TI  - Convective interaction media short monolithic columns: enabling chromatographic
      supports for the separation and purification of large biomolecules.
AB  - New therapeutics that are being developed rely more and more on large and complex
      biomacromolecules like proteins, DNA, and viral particles. Manufacturing
      processes are being redesigned and optimized both upstream and downstream to cope
      with the ever-increasing demand for the above target molecules. In downstream
      processing, LC still represents the most powerful technique for achieving high
      yield and high purities of these molecules. In most cases, however, the
      separation technology relies on conventional particle-based technology, which has
      been optimized for the purification of smaller molecules. New technologies are,
      therefore, needed in order to push the downstream processing ahead and into the
      direction that will provide robust, productive, and easy to implement methods for
      the production of novel therapeutics. New technologies include the renaissance of
      membranes, various improvements of existing technologies, but also the
      introduction of a novel concept--the continuous bed or monolithic stationary
      phases. Among different introduced products, Convective Interaction Media short
      monolithic columns (SMC) that are based on methacrylate monoliths exhibit some
      interesting features that make them attractive for these tasks. SMC can be
      initially used for fast method development on the laboratory scale and
      subsequently efficiently transferred to preparative and even more importantly to
      industrial scale. A brief historical overview of methacrylate monoliths is
      presented, followed by a short presentation of theoretical considerations that
      had led to the development of SMC. The design of these columns, as well as their
      scale-up to large units, together with the methods for transferring gradient
      separations from one scale to another are addressed. Noninvasive methods that
      have been developed for the physical characterization of various batches of SMC,
      which fulfill the regulatory requirements for cGMP production, are discussed. The
      applications of SMC for the separation and purification of large biomolecules,
      which demonstrate the full potential of this novel technology for an efficient
      downstream processing of biomolecules, are also presented.

PMID- 16276783
TI  - Peptide and peptidomimetic chiral selectors in liquid chromatography.
AB  - The application of peptide and peptidomimetic chiral selectors in LC is reviewed
      in this article. In particular, methods for finding these types of selectors
      using combinatorial library approaches are discussed, as well as recent advances
      in the use of peptides and peptidomimetics as general chiral selectors for LC. In
      terms of the library approaches, batch screening and reciprocal screening are
      discussed. As for general chiral selectors, one example involves the application
      of chiral diamide phases. Another example shows the versatility of oligoproline
      chiral stationary phases, which exhibit resolution for a number of racemic
      analytes, comparable to other well-established chiral stationary phases.

PMID- 16276787
TI  - Electric field gradient focusing.
AB  - Electric field gradient focusing (EFGF) is a relatively new separation technique
      with promising attributes, particularly for protein analysis. The fundamental
      fractionation mechanism in EFGF involves a gradient in electric field along the
      length of a separation column. The electrophoretic force that drives charged
      analytes in a region of changing electric field is opposed by a constant,
      pressure-driven bulk fluid flow. When the electrophoretic velocity of a
      particular moiety is equal and opposite to the velocity of the fluid flow, the
      analyte focuses into a stationary band. Thus, EFGF can both concentrate and
      separate charged species according to electrophoretic mobility. To date, the
      electric field gradients needed for EFGF have been established using a number of
      different approaches, including channels having changing cross-sectional areas,
      conductivity gradients caused by the diffusion of buffer ions across a membrane,
      electrode arrays, and temperature gradients in buffers whose conductivities
      change as a function of temperature. EFGF has proven particularly effective for
      sample enrichment, with concentration factors of 10,000 reported. In this article
      we review advances in EFGF technology and discuss prospects for further improving
      EFGF for chemical analysis.

PMID- 16276786
TI  - Inductively coupled plasma mass spectrometry in separation techniques: recent
      trends in phosphorus speciation.
AB  - Inductively coupled plasma-MS (ICP-MS) and its combined use with molecular mass
      spectrometric techniques have become the most promising detection techniques in
      speciation studies. High sensitivity and element specificity of ICP-MS has the
      advantage of detecting trace amounts of the species of interest in complex
      matrices. This review is divided into two parts. In the first part, suitable use
      of ICP-MS either online or offline with currently used separation techniques such
      as HPLC, CE, and gel electrophoresis in speciation analysis is briefly discussed.
      In the second part, recent applications (1999-2005) of phosphorus speciation is
      presented to elucidate the importance of ICP-MS in separation methods and to
      illustrate its importance in nonmetal detection.

PMID- 16276788
TI  - Applications of capillary electrophoresis on microchip.
AB  - CE on microchip is an emerging separation technique that has attracted wide
      attention and gained considerable popularity. Because of miniaturization of the
      separation format, CE on chip typically offers shorter analysis time and lower
      reagent consumption with potential development of portable analytical
      instrumentation. This review with 143 references is focused on proteins and
      peptides analysis, DNA separation including fragment sizing, genotyping, mutation
      detection and sequencing, and also the analysis of low-molecular-weight
      compounds, namely explosive residues and warfare agents, pharmaceuticals and
      drugs of abuse, and various small molecules in body fluids.

PMID- 16276791
TI  - Bankruptcy reform: what it means to you.

PMID- 16276792
TI  - Diabetes screening.

PMID- 16276785
TI  - New hyphenated methodologies in high-sensitivity glycoprotein analysis.
AB  - High-sensitivity glycoprotein analyses are of particular interest in modern
      biomedical and clinical research, as well as in the development of recombinant
      protein products. The evolution of new hyphenated methodologies in high
      sensitivity glycoprotein analysis is highlighted in this thematic review. These
      methodologies include, in particular, capillary LC/MALDI/TOF/TOF MS in
      conjunction with online permethylation platform, and silica-based lectin
      microcolumns interfaced to MS. The potential of these methodologies in glycomic
      and glycoproteomic analysis is demonstrated for model glycoproteins as well as
      total glycomes and glycoproteomes derived from biological samples. Additionally,
      the applications of CE-MS, CEC, and nanoLC with graphitized carbon in the areas
      of glycomics and glycoproteomics are described.

PMID- 16276794
TI  - Hospitalists: communication is key.

PMID- 16276793
TI  - Staying eye-to-eye with patients.

PMID- 16276795
TI  - So you want to be a hospitalist.

PMID- 16276797
TI  - When medicine and religion collide.

PMID- 16276796
TI  - Protect yourself against identity theft.

PMID- 16276798
TI  - Josh's bloody birthday party.

PMID- 16276799
TI  - 5 rules for managing tough patients.

PMID- 16276800
TI  - Your most powerful Rx.

PMID- 16276801
TI  - Exercise tips for your patients.

PMID- 16276802
TI  - If you're the deepest pocket.

PMID- 16276803
TI  - It pays to be positive.

PMID- 16276804
TI  - Making a difference, molding the future.

PMID- 16276805
TI  - The financial picture.

PMID- 16276806
TI  - When is a patient your patient?

PMID- 16276808
TI  - Unprepared for bird flu.

PMID- 16276807
TI  - Losing sleep.

PMID- 16276809
TI  - Informed consent: it's not just signing a form.
AB  - Informed consent plays a major role in forming a therapeutic alliance with the
      patient. The informed consent process has evolved from simple consent, in which
      the surgeon needed only to obtain the patient's permission for a procedure, into
      informed consent, in which the surgeon provides the patient with information
      about clinically salient features of a procedure, the patient understands this
      information adequately, and the patient voluntarily authorizes the surgeon to
      perform the procedure. Special circumstances of informed consent include
      conflicting professional opinions, consent with multiple physicians, patients who
      are undecided or refuse surgery, patients with diminished decision-making
      capacity, surrogate decision making, pediatric assent, and consent for the
      involvement of trainees.

PMID- 16276810
TI  - The effect of patients' noncompliance on their surgeons' obligations.
AB  - Professional oaths and codes do not establish a firm basis for the obligation to
      treat all patients and they provide little or no clear guidance about whether
      patient nonadherence exempts a physician from a longstanding and still prevalent
      tradition in surgery supports a strong obligation to one's established patients.
      A personal belief in an obligation to serve those less fortunate or even less
      compliant could support sustained treatment and special assistance to a
      nonadherent patient. A collective, professional, objective, informed decision to
      exclude a patient who is highly likely to be nonadherent or incapable of
      adherence from the benefit of a scarce resource, such as a human organ, is
      defensible and appropriate. A surgeon's decision to deny care to an established
      but nonadherent patient is much less so. Adherence is as dependent on physician
      attitude, skill, and behavior as it is on patients' nonadherence. To the degree
      that it reflects less than competent management of this prevalent problem, it can
      be considered an error or complication that makes most surgeons feel even more
      obliged to mitigate or rectify the problem. This article describes the almost
      ubiquitous phenomenon of nonadherence; a way to reconceptualize noncompliance;
      and practical steps that can help predict, prevent, identify, and manage it. It
      is hoped that this helps surgeons reduce the frequency of nonadherence, make
      dealing with it less onerous, and consequently achieve better outcomes. It is
      reasonable to think about nonadherence in terms of three roles. The surgeon's
      role is to make the patient's choice informed, to be aware of the risk factors
      for nonadherence, and not make adherence any more difficult than it has to be.
      The patient's role is to make choices between value-laden alternatives. Society's
      role is equitably to distribute scarce medical resources to patients who can and
      want to adhere to the necessary regimen to benefit from them.

PMID- 16276811
TI  - Withdrawing life-sustaining treatment: ethical considerations.
AB  - In the community of caregivers, there is a general consensus that some heroic
      measures are not obligatory in certain circumstances that are defined by
      professional norms. For example, cardiopulmonary resuscitation in terminal cancer
      patients is not endorsed because of its violation of the dignity of the
      irremediably ill, and its unproductive cost to society. Moving back from this
      extreme, the availability and effectiveness of life-prolonging treatments, such
      as ventilators, dialysis, and implantable mechanical hearts, moves into a domain
      where the boundary limit of the obligation to preserve life is less clearly
      defined. When the continuing intervention of caregivers is essential to the
      prolongation of life, but the outcome and quality of residual life has
      deteriorated far below everyone's expectations when the treatment was initiated,
      caregivers are morally troubled as their treatments prolong the process of dying.
      Uncertainty or disputation about the prognosis raises the voltage of the fear and
      potential remorse that is a normal condition of care and support at the end of
      life. Unilateral decisions and overruling of objections should be avoided when
      possible, and reinforced by legal or ethical authorities when necessary. An
      ethics consultant, especially one skilled and experienced in management of end-of
      life issues, can be a helpful negotiator and guide. The transition to palliative
      support should include the discontinuation of all unnecessary monitoring devices
      and tubes. Monitors should be turned off allowing families to direct their
      attention to the patient. Removing the monitor relieves family members from
      painful suspense and confusion. Removing the endotracheal tube sometimes allows
      conscious patients to talk to their loved ones, ending a silence forced on them
      by their treatment. If interventions are seen as masking the natural dying
      process, removing them should not be troubling. Their absence gives moral clarity
      to the elemental moments of closure at the end of life, no longer masked by
      futile contrivance. Withdrawal of life-sustaining treatment is a process that
      "merits the same meticulous preparation and expectation of quality that
      clinicians provide when they perform other procedures to initiate life support".
      Families and patients should never feel abandoned during this process and
      attention should be devoted to communicating that care is not being withdrawn.
      The family needs to be prepared for what the dying process may look like. Assure
      them that all energy is now being directed toward the comfort of the patient
      including sedation as required if signs of suffering are observed. Easing death,
      like easing birth, can be one of the most fulfilling contributions one can make
      to reduce the suffering and enrich the lives of patients and their families.
      Neglecting this part of the duty to provide appropriate care brings moral anguish
      to all participants in the peculiar circumstances that have come to surround
      death in the ICUs of developed countries. It is helpful to accept the inevitable
      reality that death is, in Shakespeare's words, a "necessary end" to all mortal
      life, and to recognize that defying death with technology can sometimes become an
      unnatural and degrading activity, however well motivated. The withdrawal of life
      sustaining treatment, when conducted expertly, is a shared human experience that
      can be gratifying, although difficult for all concerned.

PMID- 16276812
TI  - Postoperative futile care: stopping the train when the family says "keep going".
AB  - All surgeons must take risks when providing medical care. No guarantees of
      protection from a lawsuit exist in any guise. Concerning postoperative futile
      care, the stakes are high when withdrawal of support seems to be indicated but
      the surrogate believes in sanctity-of-life and demands continued aggressive care.
      Open-ended questions posed to the family may initiate a dialog that help the
      surgeon understand their values and negotiate a resolution. Other preventive
      measures can also reduce the chance of conflict and potential liability. "Do
      what's right" is a proverbial motto in surgical training and clinical practice.
      To some surgeons, it may be to honor the wishes of the family surrogate. To
      others, the right thing may be to withdraw care in the best interest of the
      patient. If so, "do what's right" is not just to "stop the train." It also
      consists of a range of clinical activities, including effective communication,
      emotional care, and pursuing a fair and open negotiation process established by
      the institution. Properly conducted, "stopping the train" should incur no greater
      risk for professional liability than any other challenging procedure that
      surgeons perform. Withdrawal of futile care should be considered as a procedure,
      and as such, the skills to deliver it should be mastered like any other.

PMID- 16276814
TI  - Solving the problem of the uninsured.
AB  - Reform of the United States health care system is less complicated than at first
      might appear. The building blocks of an ideal system are already in place. The
      federal government already generously subsidizes private health insurance and
      safety net care. What is wrong with the current system is that there are too many
      perverse incentives. One could reasonably argue that government is doing more
      harm than good, and that a laissez faire policy is better than what is now in
      place. Nonetheless, if government is going to be involved in a major way in the
      health care system, perverse incentives should be replaced with neutral ones. At
      a minimum, government policy should be neutral between private insurance and the
      social safety net, never spending more on free care for the uninsured than it
      spends to encourage the purchase of private insurance. Careful application of
      this principle would go a long way toward creating an ideal health care system.

PMID- 16276813
TI  - Ethical issues in patient safety.
AB  - Making progress in patient safety poses many challenges, practical and
      theoretical, to the way physicians practice medicine. The ethical challenges are
      among the most profound. They include the ethical imperative to do all things
      practical to prevent errors and injury to patients, the need to respond
      appropriately when things go wrong to find new methods to prevent recurrence, the
      requirement for honesty and openness in dealing with our patients when things go
      wrong, and taking responsibility for ensuring that all of our colleagues are safe
      and competent. This is an immense challenge. It is not easy to "first, do no
      harm." But only we as a profession can meet this challenge. No one else can do
      it; we must.

PMID- 16276815
TI  - Compliance with HIPAA regulations: ethics and excesses.
AB  - HIPAA regulations have been seen by many physicians as providing innumerable
      administrative hoops that require jumping through with no clear benefit for
      individual patients. Although this article has not comprehensively explored the
      requirements of HIPAA regulations, it has focused on the issues of "incidental
      disclosures" that are so important to the daily interactions of physicians and
      patients. Through the use of illustrative cases, it has been shown that HIPAA
      regulations frequently are based on well-accepted ethical principles. Although
      one should never conclude that changing something from an ethical responsibility
      to a legal responsibility makes it more important, there is no question that
      HIPAA regulations have forced physicians to consider more carefully how
      confidential information may be transmitted to others. As such, physicians should
      look on HIPAA regulations as largely supporting the use of professional judgment
      in providing good quality medical care. Although not all aspects of HIPAA are
      grounded in ethical practices, the overall thrust of the HIPAA regulations is
      consistent with the ethical practice of medicine and surgery. As a result of this
      general alignment of the legal and ethical requirements, more attention should be
      directed by physicians at using good judgment in deciding how to disclose private
      information, rather than adopting an unreasonable approach that confidentiality
      may never be breached. As Lo and colleagues have very appropriately pointed out:
      In the context of inadvertent disclosure, the legal risks of good practice are
      very low. Physicians should work with risk managers and practice administrators
      to develop policies that promote good communication in patient care, while taking
      appropriate steps to protect patient privacy. By adopting such an approach to
      HIPAA, physicians can abide by the regulations while maintaining high ethical
      standards and minimizing the impact of the new requirements on physician-patient
      relationships.

PMID- 16276816
TI  - The ethics of living donor lung transplantation.
AB  - A constant awareness of the risk to the living donors must be maintained with any
      living donor organ transplantation program, and comprehensive short- and long
      term follow-up should be strongly encouraged to maintain the viability of these
      potentially life-saving procedures. There has been no perioperative or long-term
      mortality following lobectomy for living lobar lung transplantation, and
      perioperative risks associated with donor lobectomy seem to be similar to those
      seen with standard lung resections. These risks might increase, however, if the
      procedure is offered on an occasional basis and not within a well-established
      program. The long-term outcomes and functional effects of lobar donation raise
      important questions that are unanswered. This has proved difficult to follow
      closely, because of the fact that many donors live far from the transplant
      medical center and are reluctant to return for routine follow-up evaluation. The
      death of a recipient can further exacerbate this situation, because there is
      reluctance to insist on further routine examinations for a grieving donor.
      Prospective donors must be informed of the morbidity associated with lobectomy
      and the potential for mortality, and for potential negative recipient outcomes in
      regard to life expectancy and quality of life after transplantation. Although
      cadaveric transplantation must be considered because of the risk to the donors,
      living lobar lung transplantation should continue to be used under properly
      selected circumstances. The results reported by the authors' group and others are
      important if this procedure is to be considered as an option at more pulmonary
      transplant centers in view of the institutional, regional, and international
      differences in the philosophic and ethical acceptance of the use of living organ
      donors for transplantation. The integration of ethical discussion into topics
      that are relevant and of interest to thoracic surgeons, such as living lung
      donation, is a recent and welcome event. Many of the clinical situations that
      thoracic surgeons deal with on a daily basis have important and complex ethical
      implications, and there has been little training to deal effectively with these
      issues. This is changing as invited discussions on ethically compelling topics
      are finding their way into journals and the programs of national meetings. What
      may be of more importance, however, is the development of an ethics curriculum
      for those training in the specialty. The core curriculum recommended by the
      Thoracic Surgical Directors Association (which represents the leadership of the
      89 approved residency training programs in the United States) has one lecture
      pertaining to ethics out of the several hundred offerings in its requisite
      curriculum. It is hoped that this will change in the near future.

PMID- 16276817
TI  - Conflicts in the surgeon's duties to the patient and society.
AB  - Surgeons may face a dilemma in which their obligations to their patients and
      their obligations to others or society may conflict. One way of examining these
      conflicts is through a model as depicted in Fig. 1. When both the patient and
      society are benefited (eg, in cases of routine surgical care), the surgeon may
      proceed with the planned treatment. In situations where it is agreed that both
      the patient and society will be harmed (eg, surgeon involvement in capital
      punishment or in many cases of deception), the surgeon should avoid acting in a
      manner against that of the patient. Many situations, however, involve the need to
      weigh the benefits and burdens of both the patient and society. In these cases,
      surgeons need to analyze carefully all of the ethical and legal issues involved,
      and make a decision based on their own set of values.

PMID- 16276818
TI  - Who's buying lunch: are gifts to surgeons from industry bad for patients?
AB  - Why does gifting exist in the medical marketplace? It provides a sales advantage
      in a competitive marketplace by establishing crucial relationships with the
      patients' fiduciary: the physician and surgeon. Do gifts to physicians from
      industry harm patients? One can cite mountains of indirect evidence that they do,
      and maybe in the case of recalled devices and drugs there are actual corpses, but
      these examples are retrospective and it is impossible to prove that removing
      detailing eliminates the harm. Banning gifts to surgeons would not completely fix
      the ethical problem of pharmaceutical and device marketing. Gifts are important
      because they buy access and foster relationships, but inherent bias in research
      and the medical literature makes it very difficult to remain objective. It is a
      race, and education has not kept pace with advertising; only 10% of 575 internal
      medicine physicians thought they had had sufficient training during medical
      school and residency regarding professional interaction with sales
      representatives. Would banning gifts help at all? Would enforcing an unpopular
      ethical code protect patients? There might be a small improvement, but not as
      significant as eliminating representatives and product samples altogether. This
      is not likely to happen without an enormous fight against the wealthiest industry
      in America. The solution is education. To borrow industry's argument, physicians
      and surgeons are ethical creatures with capacity for judgment and integrity. They
      need to understand and believe the magnitude of the problem. Detailing exists
      because there is a market for it, empowering surgeons with ethical training
      reduces the demand for goodies, and at some point the popular choice will be to
      buy their own lunch. Business ethics are not medical ethics. Industry is behaving
      exactly as it must to maximize profits. Although it is painful for some surgeons,
      surgical residencies, and professional organizations to envision a future with
      diminished corporate gifts, it is every surgeon's responsibility to consider
      whether their dealings with the pharmaceutical and medical equipment industries
      withstand the harsh light of realities presented herein.

PMID- 16276819
TI  - Ethical issues in surgical research.
AB  - Higher standards of evidence for surgical procedures are likely to be demanded in
      the future by health insurance providers. Consequently, more formal and rigorous
      surgical research, including RCTs, will become more prevalent. Facing the ethical
      challenges of surgical research requires understanding of the ethically
      significant differences between surgical practice and research and the ways in
      which the ethical standards appropriate for the design and conduct of clinical
      research differ from the ethics of clinical care.

PMID- 16276820
TI  - Surgically implanted devices: ethical challenges in a very different kind of
      research.
AB  - Research on surgically implanted devices not only can raise issues familiar from
      drug studies, but also can raise special challenges. This article suggests some
      ways in which device trials can raise distinctive ethical issues. The AbioCor
      artificial heart trial is used as an example. Although this particular trial
      should not be deemed typical of surgically implanted device studies, it can
      highlight some particularly significant methodologic and ethical features.

PMID- 16276821
TI  - Heart rate variability during incremental cycling exercise in healthy untrained
      young men.
AB  - BACKGROUND: Linear relationship between the increase of heart rate (HR) and the
      power output (PO) during sub-maximal exercise is well documented. However the
      study considering the effect of progressive increase of PO on the parameters of
      heart rate variability (HRV) remain scarce. AIM: This study investigated changes
      of the HRV time and spectral parameters in young, untrained men during
      incremental cycling exercise. METHODS: Fifteen young, untrained men aged 21 +/-
      1.5 years participated in our study. Preliminary medical examination excluded any
      cardiovascular diseases. The examined individuals were cycling on the cycle
      ergometer (Monark 824E, Sweden) with constant frequency, amounting to 60 rev x
      min(-1). PO was increased by 30 W every 3 minutes. ECG was recorded via shortened
      limb lead I, using Dual BIO Amp (AD Instruments, Castle Hill, Australia) hardware
      and Power Lab (AD Instruments) software. Spectral analysis of HRV was based on
      the fast Fourier transformation (FFT). The time (HR, RMSSD) and spectral (LF, HF)
      parameters were analysed within 3 minutes time periods, before the exercise and
      on each level of the generated power output. RESULTS: The exercise was performed
      until the subjects reached 80% of the HR max expected for their age. This has
      occurred at the PO = 202 +/- 33 W (mean +/- SD). Mean HR in this group showed
      linear increase (p < 0.001) with power output (90 +/- 7 bt x min(-1) at 30 W vs.
      166 +/- 11 bt x min(-1) at the power output of 202 +/- 33 W). Significant
      decrease of time parameters of the HRV (0 W vs. 202 +/- 33 W)--SDNN (p < 0.001)
      and RMSSD (p < 0.001) were observed in the analysed group. Spectral parameters of
      the HRV also presented significant reduction. Decreases of total power of the HRV
      spectrum (TP, p < 0.001), low frequency (LF, p < 0.01) and high frequency (HF, p
      < 0.01)) spectra as well as LF/HF ratio (p < 0.01) were noted. CONCLUSIONS: In
      the light of the present study, the applicability of the HRV power spectrum, with
      its present interpretation, to the assessment of the sympatho-vagal interaction
      during incremental exercise is indeed very questionable.

PMID- 16276822
TI  - Exercise tolerance and hyperinsulinemia in cardiac syndrome X.
AB  - The aim of the study was to evaluate the relationship between exercise tolerance,
      glucose and insulin levels and biochemical parameters related to endothelial
      function [endothelin-1 (ET-1), nitrite/nitrate (NOx)] in patients with
      cardiological syndrome X in comparison with healthy volunteers. The decrease of
      NOx level and NOx / ET-1 ratio suggests that endothelial dysfunction is present
      in cardiological syndrome X. Exercise tolerance correlated positively with NOx
      and negatively with insulin concentrations.

PMID- 16276823
TI  - [C-reactive protein in patients with coronary heart disease].
AB  - High-sensitive C reactive protein (hs-CRP) is a circulating acute-phase reactant
      that shows the systemic inflammation. Some prospective trials have shown that hs
      CRP is a strong predictor of future cardiovascular events. The relative risk
      associated with hs-CRP is independent of other cardiovascular risk factor.

PMID- 16276825
TI  - Functional asymmetry of pelvic floor innervation--myth or fact?
AB  - Neurophysiology of the pelvic floor is not completely understood yet. The
      importance of its symmetry and asymmetry of innervation has been pointed out
      lately. These facts have the clinical relevance in case of pelvic floor trauma or
      incontinence surgery. New techniques of EMG are necessary to confirm correlations
      between symptoms development and asymmetry of sphincter innervation.

PMID- 16276824
TI  - [Visceral sensitivity disturbances in the pathogenesis of functional
      gastrointestinal disorders].
AB  - Functional gastrointestinal disorders are common pathology of the gut. The most
      frequent of them--functional dyspepsia and irritable bowel syndrome, formally
      regarded as different entities, in the view of new research and studies of the
      afferent nervous system seem to have common triggers and result from similar
      pathophysiological mechanisms. Disorders of regulation of the two-way
      communication between brain and gut (the brain-gut axis) modulated by different
      social and environmental factors are important in the pathogenesis of these
      diseases. Damage to brain processes like perception and affective responsiveness
      can be major contributors to the pathogenesis of functional gastrointestinal
      signs.

PMID- 16276826
TI  - [Microchip neuromodulation of the autonomic system with magnetic field energy
      supply].
AB  - We describe technical solution of the problem MC magnetic field energy supply
      showing that system is effective in the neuromodulation of the vagal activity
      associated with food intake. Effect of MC on decrease of food intake were related
      to strength of the magnetic field (19-350).

PMID- 16276827
TI  - Gastric stimulation is effective in reversing vasopressin induced gastroparesis.
AB  - The aim of this study was to determine the most effective current parameters
      reversing vasopressin (VP) induced gastroparesis by gastric electrical
      stimulation IGES). METHODS: Twenty male healthy Wistar rats were included into
      the study (weight 227 +/- 24 g). Animals were subjected to gastric fistula
      placement and implantation of two monopolar electrodes for EGG-studies and GES.
      After 5 days of recovery VP was applied (terlipressin 0.1 mg/kg i.p.) The gastric
      motility was measured by means of balloon introduced into the stomach through the
      fistula. The gastric electrical and motor activity were recorded by the
      PowerLab/8SP system and software. Electrical signals were cleared by 3000 AC/DC
      differential amplifier A-M System Inc. Gastric electrical stimulation (GES) was
      generated by Zimmer stimulator SINUS5. The following currents: S01 (monopolar):
      ampl 2.2 mA, freq 29 Hz, on/off 1 s / 10 s; S02 (bipolar): ampl 2.2 mA, freq 29
      Hz, on/off 1s/10s: S03 (monopolar): ampl 2.2 mA, freq 0.5 Hz: S04 (monopolar):
      ampl 2.2 mA, freq 34 Hz, on/off 5.5 s/15 s were used. RESULTS: The phasic
      contractions almost disappeared and amplitude decreased from 12 +/- 5 to 2.9 +/-
      1.5 cm H20. The motility index decreased from 276,3 +/- 76.4 to 154.6 +/- 63 cm
      H2O x s/min. GES S01-S04 increased motility index to: 167.6 +/- 60.8: 155.1 +/-
      89.3; 170.3 +/- 92.3: 301.9 +/- 70.5 cm H2O x s/min respectively. The frequency
      of gastric slow wave increased from 0.04 +/- 0.02 to 0.07 +/- 0.02 Hz after VP
      administration. GES S01-S04 reversed VP induced increase of slow wave frequency
      to 0.06 +/- 0.02, 0.055 +/- 0.02, 0.06 +/- 0.01 and 0.04 +/- 0.02 Hz,
      respectively. CONCLUSIONS: This effectiveness of local GES and the pressure
      pattern of induced gastroparesis suggest peripheral complex inhibitory-excitatory
      action of vasopressin on gastric smooth muscles. The mechanism of this action may
      involve the enteric nervous system, gastric and vasal smooth muscles. The most
      effective in reversing VP induced functional gastroparesis is high frequency
      current applied in timing of the natural slow wave.

PMID- 16276828
TI  - [Vagal chronic stimulation decreased colonic Cajal cells density in rats].
AB  - BACKGROUND: Interstitial CaJal cells ICC) function as pacemaker cells for the
      smooth muscle of the gastrointestinal (GI) tract. They are binding muscles with
      the enteric nervous system creating network and play an important role in the
      regulation of motility of the GI tract. Previous data from our laboratory show
      that chronic vagal stimulation leads to decrease of body weight of examined
      animals. We propose, that this effect could be mediated not only by central
      mechanisms, but also is observed as a result of disturbances of peristalsis
      caused by damage o interstitial cells of Cajal (ICC). In this study we evaluate
      density of the ICC in the proximal colon in rats with chronic vagal stimulation
      (MC) microchip (1-month stimulation, frequency of 0.1 Hz). METHODS: One month
      after implantation of microchip proximal colon was taken from MC and control rats
      (n=14). An immunohistochemical method--staining with specific antibodies against
      c-kit receptor (CD117--Santa Cruz Biotechnology)--was performed. The result of
      this reaction in the region of colonic myenteric plexuses was morphometrically
      assessed using computed image analysis. RESULTS: Amount of ICC in colonic
      myenteric plexuses decreased in MC group (3.2 +/- 1.10% of muscular layer) in
      comparison to the control group (4.86 +/- 1.02% of muscular layer) (p < < 0.05).
      No differences of the other morphometrical parameters of the muscle layers in
      both groups were observed. CONCLUSION: Colon ICC count decrease in response of
      chronic vagal stimulation which confirms possibility of disturbances of colonic
      motility, but mechanism remains unclear.

PMID- 16276829
TI  - [Use of vasopressin analogues and antagonist in clinical practice].
AB  - Vasopressin is an endogenous peptide hormone with the antidiuretic and vasoactive
      action. Its mechanisms of action on vasal smooth muscles and kidney collective
      tubules are well known. This hormone also plays a role in the central nervous
      system and influences smooth muscles of the gastrointestinal tract. The recent
      research results indicated much more extensive effects of endogenous vasopressin
      action on the circulation than appeared from the water-electrolyte balance
      regulation only. The use of this hormone is actually an alternative for
      catecholamine in treatment of the shock. This paper presents short review of
      vasopressin action, actual clinical use and perspectives in use of vasopressin
      antagonists in the heart failure.

PMID- 16276830
TI  - [Risk factors of early recurrence after surgical treatment in Graves disease].
AB  - To determine the factors causing early recurrence after surgery for Graves
      disease, I've studied 81 patients who underwent subtotal thyroidectomy. Thyroid
      functional status was evaluated biochemically every 3 months. After one year the
      patients were divided into 3 categories: recurrent hyperthyroidism, euthyroidism
      and hypothyroidism. The following factors were analyzed: personal, environmental,
      antithyroid drug tolerance, indication for surgery, clinical investigation, TRAb
      serum titer, quality of surgical treatment, pathological findings. Prognostic
      factors for failure were identified by using logistic regression. The incidence
      of early hyperthyroidism was 11.1%. Significant factors for recurrence were
      goitre size <65 ml, blood group "O", positive TRAb titer, tiamazole intolerance,
      advanced exophthalmos and pregnancy for women. Basing on these factors "the risk
      scale" was created. It seems to be helpful for qualifying the selected high risk
      cases to primary total thyroidectomy.

PMID- 16276831
TI  - [Phytoestrogens: are they really safe?].
AB  - The aim of this article was to present a simple classification of phytoestrogens,
      their approximate content in food products as well as their synthesis,
      biotransformation and activity in human organism. Having various mechanisms of
      action, phytoestrogens display both beneficial and adverse effects on
      physiological processes. Several positive health effects have been associated
      with phytoestrogens, such as a protective role against the development of
      cancers, proestrogenic effects (particularly with postmenopausal women) and
      beneficial influence on cardiovascular and osseous systems. Adverse effects of
      phytoestrogens have been observed in fetuses and young specimens. Limited studies
      have displayed disorders in morphology and physiology of the male reproductive
      system. High plasma phytoestrogens level inhibits a cellular activity of some
      enzymes, e.g. enzymes involved in the synthesis of steroid hormones. Direct
      contact with exogenous, environmental estrogens depends on human diet and it can
      be variable in different populations.

PMID- 16276832
TI  - Two-tier fears in pensions battle.

PMID- 16276833
TI  - Pension victory comes with a sting in the tail.

PMID- 16276834
TI  - It is time to put a stop to health inequalities.

PMID- 16276835
TI  - Making backs better.

PMID- 16276836
TI  - How I coped with Hurricane Katrina.

PMID- 16276837
TI  - Adherence to antiretrovirals in refugees and asylum seekers.
AB  - Adherence to antiretroviral regimes is essential in effective management of HIV.
      The cultural, social, religious and immigration status of refugees and asylum
      seekers can have an impact on their understanding of their care needs and
      maintenance of their treatment regimen.

PMID- 16276838
TI  - Clinical facts. Gynaecomastia.

PMID- 16276839
TI  - Blood cells. Part four--lymphocytes and lymphoid-derived cells.

PMID- 16276840
TI  - Understanding the issues involved in requesting X-rays.
AB  - Ordering X-rays is one of the 10 key roles for nurses (DoH, 2003). Increasing
      numbers of nurses are requesting examinations involving the use of ionising
      radiations, such as X-rays and computerised tomography (CT) scans. This article
      explains some of the issues, suggests ways to go about gaining requesting rights
      and gives practical advice on the process.

PMID- 16276841
TI  - Long-acting reliever/preventer inhalers.

PMID- 16276842
TI  - Implementing the single assessment for older people.
AB  - The National Service Framework for Older People envisages that the single
      assessment process will act as a key driver in the improvement of services for
      older people. Leeds Teaching Hospitals NHS Trust implemented a form of contact
      assessment that works in both hospital and community settings.

PMID- 16276843
TI  - Optimum number of sessions for depression and anxiety.
AB  - AIM: To examine the relationship between the number of psychological treatment
      sessions completed by patients (1-5 sessions, 6-8 sessions, >8 sessions) and the
      change in self-rated depressive and anxiety symptoms using the Hospital Anxiety
      and Depression Scale (HADS). METHOD: Recording demographic characteristics and
      various clinical outcome measures for all referrals to the service and examining
      the relationship between changes in self-reported anxiety and depression
      symptoms. RESULTS: For depression, the study shows that having 6-8 sessions
      offers more benefit than 1-5 sessions. Having more than eight sessions does not
      confer any additional benefit. Indeed, there is little difference between 1-5
      sessions and more than eight sessions for depression. For anxiety, symptoms
      appear to continue to improve with increasing numbers of treatment sessions.
      CONCLUSION: Beyond eight treatment sessions, there appears to be no additional
      improvement. This is not the case for anxiety, where continuing treatment
      sessions appear to reduce symptoms.

PMID- 16276844
TI  - Nursing Times top 100 nursing employers.

PMID- 16276845
TI  - How to ensure you pass an OSCE.

PMID- 16276846
TI  - Psychiatric epidemiology in Canada and the CCHS study.

PMID- 16276847
TI  - The Canadian Community Health Survey: mental health and well-being.
AB  - As part of the Canadian Community Health Survey (CCHS) biennial strategy, the
      provincial survey component of the first CCHS cycle (Cycle 1.2) focused on
      different aspects of the mental health and well-being of Canadians living in
      private dwellings. Moreover, the survey collected data on prevalences of specific
      mental disorders and problems, use of mental health services, and economic and
      personal costs of having a mental illness. Data collection began in May 2002 and
      extended over 8 months. More than 85% of all interviews were conducted face-to
      face and used a computer-assisted application. The survey obtained a national
      response rate of 77%. This paper describes several key aspects of the
      questionnaire content, the sample design, interviewer training, and data
      collection procedures. A brief overview of the CCHS regional component (Cycle
      1.1) is also given.

PMID- 16276848
TI  - Unmet need for the treatment of depression in Atlantic Canada.
AB  - OBJECTIVE: Most people with depression do not receive treatment, even though
      effective interventions are available. Population-based data can assist health
      service planners to improve access to mental health services. This study aimed to
      examine the determinants of untreated depression in Canada's Atlantic provinces.
      METHOD: This study used data from the Canadian Community Health Survey Cycle 1.1.
      Logistic regression models explored the prevalence of depression and associated
      patterns of mental health service use among population subgroups. RESULTS: Of the
      respondents, 7.3% experienced major depression in the previous year, as measured
      by the Composite International Diagnostic Interview Short Form. Individuals with
      the following characteristics were at increased risk for depression: female sex;
      widowed, separated, or divorced marital status; low income; and 2 or more
      comorbid medical conditions. Only 40% of respondents with probable depression
      reported any consultation about their condition with a general practitioner or
      mental health specialist. Less than one-quarter of Atlantic Canadians with
      depression reported receiving levels of care consistent with practice guidelines.
      Vulnerable groups, including older individuals, people with low levels of
      education, and those living in rural areas, were significantly less likely to
      receive treatment in either primary or specialty care. CONCLUSIONS: These
      findings suggest inequitable access to services and the need to target
      interventions to at-risk populations by raising awareness among the public and
      health care providers. Health systems in the Atlantic region must work toward
      achieving consistent longitudinal care for a larger proportion of individuals
      suffering from depression by studying the underlying factors for service use
      among underserved groups.

PMID- 16276849
TI  - Area variations in the prevalence of substance use and gambling behaviours and
      problems in Quebec: a multilevel analysis.
AB  - OBJECTIVES: This study aimed to examine whether variations among regions in
      Quebec existed after we controlled for individual characteristics in the
      prevalence of 1) alcohol, cannabis, and gambling behaviours and 2) substance
      related disorders and pathological gambling. METHODS: Using data derived from the
      Canadian Community Health Survey: Mental Health and Well-Being (CCHS 1.2), we
      nested 5332 respondents from the province of Quebec within 374 regions equivalent
      to census subdivisions (CSDs). Outcome variables included 1) drinking status
      (past 12 months), alcohol consumption (last week), and 12-month diagnosis of
      alcohol dependence; 2) cannabis use (past 12 months and lifetime) and diagnosis
      of illicit drug dependence; and 3) gambling status, severity of gambling
      problems, and number of reported gambling activities (past 12 months). Multilevel
      regression models with individuals (Level 1) nested in regions (CSDs, Level 2)
      assessed the variations among regions in the prevalence of various outcomes and
      disorders when individual characteristics were controlled for. RESULTS: Variance
      component models revealed that all alcohol-related variables, the prevalence of
      cannabis use (12 months), and problem gambling did not vary among areas. Gambling
      rates and the average number of reported gambling activities varied among areas,
      even when individual-level variables were accounted for in the models, whereas
      for lifetime cannabis use, variations among areas became nonsignificant.
      CONCLUSION: Intervention programs may need to address the environment as a
      relevant determinant of health-related behaviours and lifestyles.

PMID- 16276850
TI  - Is the statistical association between sex and the use of services for mental
      health reasons confounded or modified by social anchorage?
AB  - OBJECTIVE: Confounding and interaction have differing implications for the
      interpretation of findings and the design of research, mental health services,
      and policy. This study aimed to verify whether the association between sex and
      the use of services for mental health reasons is confounded or modified by social
      anchorage. METHODS: We undertook a case-control study nested in Cycle 1.2 of the
      Canadian Community Health Survey. Cases were defined as users of general medical
      services for mental health reasons in the previous 12 months, and control
      subjects were defined as never-users of any services for mental health reasons.
      The pattern of social anchorage was described by the roles of parent, spouse,
      worker, and their combination. RESULTS: Overall, women are 2.9 times more likely
      than men to use general services for mental health reasons. However, this
      inequality between women and men decreases substantially or subsides in
      individuals who are less anchored to Canadian society. For instance, in single
      parents and in unemployed parents, the odds of using general services for mental
      health reasons are similar in women and in men. The pattern of social anchorage
      tends to modify, but not to confound, the association between sex and the use of
      services. CONCLUSIONS: Ignoring the interaction between sex and the pattern of
      social anchorage distorts the interpretation of the inequality between women and
      men in the use of general medical services for mental health reasons and may
      affect the design of comprehensive mental health services and policy.

PMID- 16276851
TI  - Psychotropic medication use in Canada.
AB  - BACKGROUND: Psychotropic medication use can be employed as an indicator of
      appropriate treatment for mental disorders. The Canadian Community Health Survey:
      Mental Health and Well-Being (CCHS 1.2) offers the first opportunity to
      characterize Canadian psychotropic medication use on a national level within
      diagnostic groups as assessed by a full version of the Composite International
      Diagnostic Interview (CIDI). METHOD: We assessed the prevalence of
      antidepressant, sedative-hypnotic, mood stabilizer, psychostimulant, and
      antipsychotic use over 2 days overall and in subgroups defined by CIDI-diagnosed
      disorders and demographics. We employed sampling weights and bootstrap methods.
      RESULTS: Overall psychotropic drug utilization was 7.2%. Utilization was higher
      for women and with increasing age. With any lifetime CIDI-diagnosed disorder
      assessed in the CCHS 1.2, utilization was 19.3%, whereas without such disorders,
      it was 4.1%. Selective serotonin reuptake inhibitors (SSRIs) were the most
      commonly used antidepressants for those with a past-year major depressive episode
      (17.8%), followed by venlafaxine (7.4%). Among people aged 15 to 19 years,
      antidepressant use was 1.8% overall and 11.7% among those with past-year
      depression; SSRIs made up the majority of use. Sedative-hypnotics were used by
      3.1% overall, increasing with age to 11.1% over 75 years. CONCLUSIONS:
      International comparison is difficult because of different evaluation methods,
      but antidepressant use may be higher and antipsychotic use lower in Canada than
      in recent European and American reports. In light of the relative lack of
      contemporary evidence for antidepressant efficacy in adolescents, it is likely
      that antidepressant use among those aged 15 to 19 years will continue to decline.
      The increased use of sedative-hypnotics with age is of concern, given the
      associated risk of adverse effects among seniors.

PMID- 16276852
TI  - Service use for mental health reasons: cross-provincial differences in rates,
      determinants, and equity of access.
AB  - OBJECTIVES: In 2002, Canada undertook its first national survey on mental health
      and well-being, including detailed questioning on service use. Mental disorders
      may affect more than 1 person in 5, according to past regional and less
      comprehensive mental health surveys in Canada, and most do not seek help.
      Individual determinants play a role in health resource use for mental health (MH)
      reasons. This study aimed to provide prevalence rates of health care service use
      for MH reasons by province and according to service type and to examine
      determinants of MH service use in Canada and across provinces. METHODS: We
      assessed the prevalence rate (95% confidence interval [CI]) of past-year health
      service use for MH reasons, and we assessed potential determinants cross
      sectionally, using data collected from the Statistics Canada Canadian Community
      Health Survey: Mental Health and Well-Being (CCHS 1.2). We estimated models of
      resource use with logistic regression (using odds ratios and 95%CIs). RESULTS:
      The prevalence of health service use for MH reasons in Canada was 9.5% (95%CI,
      9.1% to 10.0%). The highest rates, on average, were observed in Nova Scotia
      (11.3%; 95%CI, 9.6% to 13.0%) and British Columbia (11.3%; 95%CI, 10.1% to
      12.6%). The lowest rates were observed in Newfoundland and Labrador (6.7%; 95%CI,
      5.3% to 8.0%) and Prince Edward Island (7.5%; 95%CI, 5.8% to 9.3%). In Canada,
      the general medical system was the most used for MH reasons (5.4%; 95%CI, 5.1% to
      5.8%) and the voluntary network sector was the least used (1.9%; 95%CI, 1.7% to
      2.1%). No difference was observed in the rate of service use between specialty MH
      (3.5%; 95%CI, 3.2% to 3.8%) and other professional providers (4.0%; 95%CI, 3.7%
      to 4.3%). In multivariate analyses, after adjusting for age and sex, the presence
      of a mental disorder was a consistent predictor of health service use for MH
      across the provinces. CONCLUSIONS: There is up to a twofold difference in the
      type of service used for MH reasons across provinces. The primary care general
      medical system is the most widely used service for MH. Need remains the strongest
      predictor of use, especially when a mental disorder is present. Barriers to
      access, such as income, were not identified in all provinces. Different
      sociodemographic variables played a role in service seeking within each province.
      This suggests different attitudes toward common mental disorders and toward care
      seeking among the provinces.

PMID- 16276853
TI  - Correlates of depressive and anxiety disorders among young Canadians.
AB  - OBJECTIVE: The current study presents data on the prevalence of depressive and
      anxiety disorders in the Canadian population aged between 15 and 24 years and
      examines their potential correlates. METHODS: The study is based on the 2002
      Canadian Community Health Survey: Mental Health and Well-Being (CCHS 1.2). This
      survey was administered to a representative sample of 36,984 Canadians. A
      subsample of 5673 Canadians aged between 15 and 24 years was available for the
      analyses. We used descriptive analyses to calculate lifetime and 12-month
      prevalence of depressive and anxiety disorders, and we used logistic regressions
      to measure odds ratios. RESULTS: Among Canadian youths, 10.2% had suffered from
      depressive disorders during their lifetime, whereas 12.1% had suffered from
      anxiety disorders. For 12-month prevalence, the rates were 6.4% and 6.5% for
      depressive and anxiety disorders, respectively. Depressive disorders were more
      frequent among youth aged 20 to 24 years and among those no longer in school.
      Both disorders were more common among women and people under extreme stress.
      CONCLUSIONS: The prevalence rates found are comparable with other studies, and
      most of the correlates are concordant with the literature. Results indicate that
      there is a turning point for depression between late adolescence and adulthood
      that could be crucial for intervention planning.

PMID- 16276854
TI  - Determinants of service use among young Canadians with mental disorders.
AB  - OBJECTIVE: To identify the determinants of service use by young Canadians with
      mental health problems. METHODS: Data were drawn from a recent large Canadian
      mental health survey. The analyses were conducted on a subsample of 1092
      Canadians aged 15 to 24 years and identified as presenting a mood disorder, an
      anxiety disorder, or a substance-related disorder in the 12 months preceding the
      survey. We classified variables potentially associated with any type of service
      use for a mental health problem over a 12-month period according to predisposing,
      enabling, and need factors. We conducted weighted multivariate logistic
      regressions to determine the association of each factor with service use.
      RESULTS: In the final model, being female and living alone were the predisposing
      factors associated with service use. None of the enabling factors predicted help
      seeking. In regard to the perceived need factors, those who had difficulties with
      social situations were more likely to use services. Having a mood disorder and
      (or) having a diagnosed chronic illness were the evaluated need factors
      associated with service use. CONCLUSION: Certain groups of young Canadians are
      less likely to seek help for mental health problems and could be the target of
      interventions aimed at increasing service use.

PMID- 16276855
TI  - Variations in the prevalence of psychiatric disorders and social problems across
      Canadian provinces.
AB  - OBJECTIVE: To determine provincial 12-month prevalence rates for selected
      psychiatric disorders and to assess the association between these and the
      Canadian Social Problem Index (SPI). METHOD: Psychiatric data for depression,
      mania, panic disorder, social phobia, and agoraphobia were derived from the
      results of the 2002 Canadian Community Health Survey: Mental Health and Well
      Being. The Canadian SPI was updated for 2002, and correlations were calculated
      between the SPI and the 5 diagnostic prevalence values across provinces. RESULTS:
      The results showed that the SPI had maintained its tendency to increase from east
      to west in Canada, a trend reflected by depression and mania. The psychiatric
      disorders did not show strong correlations with the SPI in 2002, but depression
      and mania did show relatively strong associations with index values from earlier
      years. High-to-low ratios across provinces for individual social problems
      averaged over 5, and the results were essentially of the same magnitude for the
      ranges of particular psychiatric diagnoses. CONCLUSIONS: The differences in need
      found here suggest that per capita allocation of funding for mental health and
      social programs may not be appropriate. The mixed findings on the association
      between mental disorders and social problem behaviour across provinces leads to
      more research questions than research answers.

PMID- 16276856
TI  - Perceived need for mental health treatment in a nationally representative
      Canadian sample.
AB  - OBJECTIVE: The optimal method of determining how many people in the general
      population need help for emotional problems remains unclear. This study aimed to
      examine the prevalence and correlates of self-perceived need for mental health
      services (that is, help seeking and perceived need) in a large, population-based
      sample. METHODS: Data came from the Canadian Community Health Survey 1.2 (n =
      36,816, respondent age 15 years and over, and response rate 77%). Respondents
      were asked whether they had sought help in the past year from any professional
      for emotional problems and whether they felt they needed help for emotional
      symptoms but had not sought treatment. The Composite International Diagnostic
      Interview (CIDI) was used to make DSM-IV mental disorder diagnoses. RESULTS: The
      past-year prevalences of help seeking and perceived need were 8.7% and 2.9%,
      respectively. After adjusting for the presence of DSM-IV disorders assessed in
      the survey, sociodemographic factors, illness severity, social supports, and the
      presence of physical health conditions were associated with help seeking and
      perceived need. Independent of DSM diagnoses, sociodemographics, and social
      supports, perceived need and help seeking were associated with increased levels
      of distress, disability, and suicidal ideation and attempts. CONCLUSIONS: This
      study illustrates that, in addition to the presence of a DSM diagnosis, the
      respondent's self-perceived need for mental health treatment is important in the
      assessment of need for mental health services in the community.

PMID- 16276857
TI  - Help-seeking behaviours of individuals with mood disorders.
AB  - OBJECTIVES: This study had the following objectives: 1) to estimate the 12-month
      prevalence of conventional and unconventional mental health service use by
      individuals with major depressive disorder (MDD) or mania in the past year, and
      2) to identify factors associated with the use of conventional mental health
      services by individuals with MDD or mania in the past year. METHODS: We examined
      data from the Canadian Community Health Survey: Mental Health and Well-Being
      (CCHS 1.2). Respondents with MDD (n = 1563) or manic episodes (n = 393) in the
      past 12 months were included in this analysis. RESULTS: An estimated 63.9% of
      respondents with MDD and 59.0% of those with manic episodes reported having used
      some type of help in the past 12 months; 52.9% of those with MDD and 49.0% of
      those with manic episodes used conventional mental health services. Approximately
      21% of respondents with either MDD or manic episodes used natural health products
      specifically for emotional, mental health, and drug or alcohol use problems.
      Respondents who reported comorbid anxiety disorders and long-term medical
      conditions were more likely to have used conventional mental health services.
      CONCLUSIONS: Relative to previous Canadian literature, our analysis suggests that
      the frequency of conventional mental health service use among persons with MDD
      has not increased significantly in the past decade. Further, the rate of
      conventional mental health service use by persons with manic episodes is
      unexpectedly low. These findings may reflect the lack of national initiatives
      targeting mood disorders in Canada. They have important implications for planning
      future education, promotion, and research efforts.

PMID- 16276858
TI  - Comorbidity of major depression with substance use disorders.
AB  - OBJECTIVES: In the Canadian adult population, we aimed to 1) estimate the 12
      month prevalence of major depressive disorder (MDD) in persons with a diagnosis
      of harmful alcohol use, alcohol dependence, and drug dependence; 2) estimate the
      12-month prevalence of harmful alcohol use, alcohol dependence, and drug
      dependence in persons with a 12-month and lifetime diagnosis of MDD; 3) identify
      socioeconomic correlates of substance use disorder-major depression comorbidity;
      4) determine how comorbidity impacts the prevalence of suicidal thoughts; and 5)
      determine how comorbidity affects mental health care used. METHODS: We examined
      data from the Canadian Community Health Survey: Mental Health and Well-Being
      (CCHS 1.2). RESULTS: The 12-month prevalences of MDD in persons with a substance
      use disorder (SUD) were 6.9% for harmful alcohol use (95% confidence interval
      [CI], 5.2 to 8.5), 8.8% for alcohol dependence (95%CI, 6.6 to 11.0), and 16.1%
      for drug dependence (95%CI, 10.3 to 21.9). Conversely, the 12-month prevalences
      of harmful alcohol use, alcohol dependence, and drug dependence in persons with a
      12-month diagnosis of MDD were 12.3% (95%CI, 9.4 to 15.2), 5.8% (95%CI, 4.3 to
      7.3), and 3.2% (95%CI, 2.0 to 4.4), respectively. Regression modelling did not
      identify any socioeconomic predictors of SUD-MDD comorbidity. Substance
      dependence and MDD independently predicted higher prevalence of suicidal thoughts
      and mental health treatment use. CONCLUSIONS: SUDs cooccur with a high frequency
      in cases of MDD. Clinicians and mental health services should consider routine
      assessment of SUDs in depression patients.

PMID- 16276859
TI  - Larger role in disaster planning seen for quality managers. Skills in planning,
      safety seen as assets for emergency management.
AB  - Systems knowledge is essential, but so is the ability to scale back demands in
      light of reality. All disaster planning must be done in the context of providing
      optimal, safe patient care. Bureaucracy may be first casualty in quality
      manager's response to a sudden disaster.

PMID- 16276860
TI  - A new compliance reality when disaster strikes. Concentrate on providing safest,
      best care.

PMID- 16276861
TI  - To evacuate or not to evacuate. Communication will help make decision easier.

PMID- 16276862
TI  - ICU patients at risk for preventable errors. AHRQ study puts spotlight on adverse
      events.
AB  - More than 90% of events occurred during routine care. Most common medication
      error involved giving patients the wrong dose. Surprisingly, most of the errors
      involved lapses of care, which are more readily preventable.

PMID- 16276863
TI  - Program improves care, hospital collaborations. Surveys measured family stress
      level.
AB  - Significant impact seen in degree to which families feel involved in decision
      making. Stress levels of family members reduced when they receive information or
      services. Staff identification and referrals of families in need of services also
      increase.

PMID- 16276864
TI  - [A new species of the genus Phenylobacterium for the degradation of LAS (linear
      alkylbenzene sulfonate)].
AB  - A strain GZ6 that can biodegrade LAS (Linear Alkylbenzene Sulphonate) is
      identified. It is aerobic gram-negative rod or short-rod (0.5 to 0.8 by 1.0 to
      2.0 Mm). It is mobile with a single polar flagellum. Optimum growth occurred at
      30 degrees C and pH7.0. It is catalase positive, urease positive, and arginine
      decarboxylase positive. All the other physiological and biochemical tests
      performed were negative. It utilizes the xenobiotic compounds chloridazon,
      antipyrin and LAS as sole carbon sources. Most sugars, alcohols, and carboxylic
      acids are not utilized. It has Q-10 as the major quinone. The main cell fatty
      acids are Sum7, C16:0 and Sum4. The DNA G + C mol % content is 70.10. A
      phylogenic tree was constructed on the basis of 16S rDNA sequences. It showed
      that the previously known member of the genus Phenylobacterium, Phenylobacterium
      mobile DSM1986T, is the nearest neighbor to strain GZ6. The level of binary
      sequence similarity between them is 97.49%. And the DNA-DNA relatedness is 40%.
      These genetic analysis and their morphological difference show that they are
      different species of Phenylobacterium. A new species, Phenylobacterium mobile sp.
      nov., has been proposed.

PMID- 16276865
TI  - [Fusion expression of the ORF5 gene of porcine reproductive and respiratory
      syndrome virus in insect cells].
AB  - A 0.75kb fragment containing the complete cDNA of glutathione-S-transferase (GST)
      and a modified thrombin cleavage sites were amplified and cloned into pFastBacl,
      the donor plasmid of Bac-to-Bac baculovirus expression systems, downstream from
      the polyhedrin promoter (pPolh), resulting in the GST fusion transposition
      plasmid pFGST. After transposition and transfection, SDS-PAGE analysis showed
      that the developed GST fusion expression system can highly express GST. The
      signal sequences of the major structural protein gene ORF5 of porcine
      reproductive and respiratory syndrome virus (PRRSV) strain YA was removed by PCR
      and the truncated ORF5 gene was inserted into pFGST and fused with GST to
      generate the transposition plasmid expressing GST-ORF5 fusion protein. The
      recombinant baculovirus rvBacGST53 was obtained by transposition and
      transfection. GST-ORF5 fusion protein was identified by SDS-PAGE and Western
      blot. The fusion protein is 45kD and is specific to the monoclonal antibody
      against the E protein of PRRSV. The fusion protein was directly injected into
      mice and the anti-sera can react with the PRRSV-infected MARC-145 cells by
      indirect immunofluorescent assay (IFA), indicating that the fusion protein have
      better immunogenicity.

PMID- 16276866
TI  - [Construction of pseudorabies virus SH strain with gE-gI gene partial deletion
      mutant including GFP reporter gene].
AB  - On the basis of cloning and indentifying gE-gI gene of pseudurabie virus SH
      strain, the transfer plasmid vector was constucted in order to get the gE-gI gene
      partial deletion mutant. At first, gE gene and gI gene were cloned into pUC18,
      constructed the pgEI vector. Then, the 5' terminal sequence of gE gene was
      deleted 363bp using the restrict endonuclease in gE gene. The GFP expressing
      cassette was inserted into the deleting site. The recombinant plasmid pgEI
      including GFP reporter gene deleted part of gE-gI gene was constructed. BHK-21
      cell which was infected with PRV-SH for 1-2h were tansfected with the complex of
      pgEI-GFP and DOTAPA deletion mutant was selected and purified many times in BHK
      21 cell through GFP. Inoculation of mice with 2.0X107 PFU of the recombinant
      virus revealed that mice were partly protected against challenge with PRV-SH
      containing 2MLD.

PMID- 16276867
TI  - [Molecular cloning and sequencing of Dendrolimus punctatus Wenshanensis
      cytoplasmic polyhedrosis virus (DpwCPV) NS5 protein gene].
AB  - DpwCPV were purified from infected Dendrolimus punctatus Wenshanensis larvae by
      density gradient centrifugation. The genomic dsRNA segments were subsequently
      extracted directly from the purified polyhedra by SDS treatmen, phenol/chloroform
      extraction and ethanol precipitation. Defferent segments of genomic dsRNA were
      separated by low melting point agarose electrophoresis, and S9 dsRNA was purified
      after being excised from the gel. S9 RNA was denaturalized in high temperature.
      The primers was designed on the basis of the RNA sequence of S9 in BmCPV-1 (H
      strain). After RT-PCR, the amplified cDNA was cloned into the pMD18-T Vector. The
      NS5 protein gene of DpwCPV is found to be 977 nucleotides in length with one open
      reading frame in one strand. It can code a predicted protein of 320 residues
      (35560).

PMID- 16276868
TI  - [Screening of proteins anti-tobacco mosaic virus in Pleurotus eryngii].
AB  - Proteins were obtained by ion-exchange chromatography and gel filtration from the
      dry sample of Pleurotus eryngii. In terms of detection on local lesion host,
      these components were confirmed to be anti-TMV and their inhibition rates reach
      more than 70%, or even 99%. The protein named xb68Ab of MW 23.7kD was purified by
      ion-exchange chromatography and gel filtration its inhibition rate against TMV
      are 99.43% and 98.9% on Nicotiana glutionosa and Chenopodium amaranticolor,
      respectively.

PMID- 16276869
TI  - [The immuno-protect study of a hepatitis E virus ORF2 peptide expressed in E.
      coli].
AB  - A hepatitis E virus (HEV) ORF2 peptide expressed in an unfused pattern in E.
      coli, NE2, can self-assembly into homodimers and oligomers, and the immuno
      reactivity of the dimers or oligomers to HEV infected serum is much stronger than
      monomer, which suggested that some important conformational epitopes be better
      exposed in dimer or oligomer form. Three Rhesus monkeys were vaccinated with
      three doses (10 microg/dose) purified NE2 in Freud's adjuvant under a schedule of
      Od, 10d, and 30d. Specific antibodies can be detected on second week, and on
      sixth week while virus challenge were performed with 106 PCR titer of virus
      positive stool suspention, the antibody titer of one monkey was 1: 100 000, the
      other two were both 1: 20 000. Three monkeys in control group presented typical
      acute hepatitis E manifestation: increased seral amino transferase (ALT),
      antibody conversion, and continuous virus excretion in stool. In contrast, the
      ALT of monkeys in vaccinated group continued to be normal, stool virus had not
      been detected in one monkey, and presented only a short duration in another two.
      One NE2-vaccinated monkey serum with antibody titer 1: 20 000 was first incubated
      with HEV (10(3) PCR titer) for neutralization, then the mixture were used to
      challenge two monkeys, the results showed that two monkeys in control group
      continued to excrete virus for more than three weeks, sera antibody conversion,
      and one monkey presented obvious ALT increase. Both two monkeys challenged with
      antibody neutralized virus had not detected virus in stool, the antibodies
      decreased slowly, and ALT continued to be normal. These results suggested that
      the prokaryotic expression recombinant protein NE2 have good immunogenicity and
      immunoprotectivity, and should be a good candidate for an effective hepatitis E
      vaccine.

PMID- 16276870
TI  - [The fusion and expression of genes encoding heat-stable and heat-labile
      enterotoxins of escherichia coli from porcine origin].
AB  - The genes encoding precursor heat-stabile (pro-ST) and mature peptide of B unit
      of heat-labile (LT) enterotoxins of Escherichia coli from piglet were amplified
      by polymerase chain reaction (PCR). The 3' terminus of gene encoding pro-ST was
      genetically fused to the 5' terminus of the LTB subunit gene in nest-PCR. The
      fusion genes encoding pro-ST and LTB were cloned into pGEM-T vector and subcloned
      into the pQE30. The recombinant plasmid was expressed in E. coli by IPTG
      induction. The fusion protein possessed both ST and LTB antigenicity, as well as
      it had lost the biological toxicity of ST or LT toxin.

PMID- 16276871
TI  - [Identification and functional characterization of sawE--a gene involved in
      differentiation of Streptomyces ansochromogenes 7100].
AB  - A 2.8kb DNA fragment including whiB-like gene was cloned from the partial DNA
      library of Streptomyces ansochromogenes 7100 by using whiB of Streptomyces
      coelicolor J1501 as a probe. The nucleotide sequence of 1.4kb DNA fragment was
      determined and analyzed. The result showed that the fragment contains one
      complete open reading frame-designated sawE. sawE shows strong identity to whiB,
      an essential gene for early stage of sporulation. The deduced product of sawE
      gene is a regulatory protein. sawE disruptant was blocked at aerial hyphae stage
      of Streptomyces ansochromogenes 7100, no sporulation septation, no formation of
      grey mature spore. Disruptants maintained white phenotype on prolonged
      incubation. The result indicated that sawE is essential for the morphological
      differentiation of S. ansochromogenes.

PMID- 16276872
TI  - [Cloning, expression and transcriptional analysis of biotin carboxyl carrier
      protein gene (accA) from Amycolatopsis mediterranei U32 ].
AB  - Acetyl CoA carboxylase (EC 6.4.1.2, ACC) catalyzes the ATP-dependent
      carboxylation of acetyl CoA to yield malonyl CoA, which is the first committed
      step in fatty acid synthesis. A pair of degenerate PCR primers were designed
      according to the conserved amino acid sequence of AccA from M. tuberculosis and
      S. coelicolor. The product of the PCR amplification, a DNA fragment of 250bp was
      used as a probe for screening the U32 genomic cosmid library and its gene, accA,
      coding the biotinylated protein subunit of acetyl CoA carboxylase, was
      successfully cloned from U32. The accA ORF encodes a 598-amino-acid protein with
      the calculated molecular mass of 63.7kD, with 70.1% of G + C content. A typical
      Streptomyces RBS sequence, AGGAGG, was found at the - 6 position upstream of the
      start codon GTG. Analysis of the deduced amino acid sequence showed the presence
      of biotin-binding site and putative ATP-bicarbonate interaction region, which
      suggested the U32 AccA may act as a biotin carboxylase as well as a biotin
      carrier protein. Gene accA was then cloned into the pET28 (b) vector and
      expressed solubly in E. coli BL21 (DE3) by 0.1 mmol/L IPTG induction. Western
      blot confirmed the covalent binding of biotin with AccA. Northern blot analyzed
      transcriptional regulation of accA by 5 different nitrogen sources.

PMID- 16276873
TI  - [RT--PCR analysis of Phanerochaete chrysosporium lip genes in colonized fir
      wood].
AB  - Expression of Phanerochaete chrysosporium lip A2 (GLG3) lip C1 (GLG2) lip C2
      (GLGS) lipD2( GLG1), lipE (LP0811) genes were analyzed by RT-PCR method. It was
      showed that some genes were expressed in special colonized period. Only lip A2
      (GLG3) transcription occured in the 2nd week and the 8th week, both lip C1 (GLG2)
      and lip D2 (GLG1) gene transcription was checked out in the period of 6 weeks.
      However, no lip genes were expressed in the time of 4 weeks. These results
      indicated that lip gene expression is relied on the colonized period and
      transcript patterns are re dramatically different from those in previous studies
      with defined media.

PMID- 16276874
TI  - [Purification and properties of laccase from Basidiomycete].
AB  - Laccase produced by Basidiomycete was purified to electrophoretic homogeneity by
      the steps of ammonium sulfate precipitation, DEAE-cellulose and hydrophobic
      interaction column chromatography. Purification of about 318.4 fold was achieved
      with an overall yield of 18.6%. Its molecular weight was estimated to be about
      60.3 kD by SDS-PAGE, and that of it was 55.94 kD by mass spectrum. The optimum
      temperature and pH of the enzyme activity were 65 degrees C and 2.2 - 2.8
      respectively. The isoelectric point was 4.02 (room temperature). Its N-terminal
      sequence was AIGPVTDL. The carbohydrate content was 49.2% by the phenol-sulfuric
      acid method. Michaelis constant of the enzyme for ABTS was 17.5 micromol/L. The
      enzyme activity was stable under 45 degrees C and in the pH range of 3.0 - 9.5.
      The activity was enhanced by Cu2+, and was strongly inhibited by Fe2+. While Mn2+
      and Ag+ had no effect on laccase activity. Dithiothreitol and sodium azide
      inhibited completely the activity. Trp was possible essential residue for enzyme
      activity.

PMID- 16276875
TI  - [Selection of A strain producing beta-lactam antibiotics acylases].
AB  - A series of substrates analogues containing the same or similar side chain of its
      substrate have been synthesized and applied to screen cephalosporin acylase
      producers from a mass of microorganisms. The deacylation products of these
      analogues can be detected conveniently and used as screening indicators for the
      cephalosporin-acylase-producing-microorganism. Six strains possessing deacylation
      activity have been screened out with these substrate analogs. Among them, strain
      ZH0650 can simultaneously hydrolyze GL-7ACA, NIPAB and other analogues including
      AD-NABA. Further investigation on this strain confirmed that it could produce at
      least three acylases, ADNABA acylase, penicillin G acylase and cephalosporin
      acylase, which were characterized by bioassay with multiple substrate analogues.
      This is the first report that three different acylases were produced by one
      strain.

PMID- 16276877
TI  - [Preliminary study of characteristics of a special Nitrosomonas].
AB  - A special obligately-autotrophic Nitrosomonas was isolated from high temperature
      and hypersaline drainage water obtained off a wastewater treatment plant. It was
      Gram-negative, nonsporulating, ellipsoidal or short-rod shaped bacterium that
      singly arranged or arranged in a circle or in a row. Cells were 0.7 to 0.9 microm
      wide and 1.2 to 1.98 microm long. Electron-microscopic scanning of these cells
      indicated that they were wrapped by unknown fluff-like matter. They oxidized
      ammonium to nitrite and caused the removal of nitrogen from the system. But the
      decrease of NH4+ -N did not accord with the increase of NO2 - -N and NO3- -N was
      almost not detected. After 12 d of cultivation at 50 degrees C, about 10% of the
      NH4+ -N was converted to NO2- -N, 15% remained as NH4+ -N, and the other 75% was
      removed from the system, including 17% of NH4+ -N volatilized.

PMID- 16276876
TI  - [A dicarboxylate monoamide amidohydrolase (half-amidase) from Alcaligenes
      eutrophus 112R4].
AB  - A dicarboxylate monoamide amidohydrolase (half-amidase) was identified from a
      cyclicimide-metabolizing microorganism, Alcaligenes eutrophus 112R4. The enzyme
      catalyzed the hydrolysis of monoamidated dicarboxylates, which were the
      hydrolyzing products of cyclic imides by imidase, to dicarboxylates and ammonia.
      The enzyme showed high catalytic activity to succinamic acid, but no obvious
      activity to aliphatic amides, amino acid amides, N-carbamoyl amino acids and urea
      was observed. The productions of half-amidase and imidase were correlative in
      Alcaligenes eutrophus 112R4, in that succinimide and succinamic acid enhanced the
      expressions of these two enzymes simultaneously, while free ammonia repressed
      their expressions. Succinate showed regulation effects on either synthesis or
      activities of half-amidase and imidase. The characteristics of half-amidase were
      investigated by using the crude extract of recombined E. coli cell. The fact that
      cobalt ion stimulated the activity of half-amidase by a coefficient of 3.37,
      implied that half-amidase was probably a metal-binding enzyme.

PMID- 16276878
TI  - [The breeding of high glutathione-producing strain and optimization of culture
      condition].
AB  - High glutathione-producing strain ZJF-71 was constructed by primary
      screening,isolation of haploid, mutagenesis and protoplasts fusion. The yield of
      glutathione of the fusant ZJF-71 is 1.59 and 1.42 times that of the parental
      strains Y64 and Y247, respectively. The factors that affected the biomass and
      glutathione content of the fusant ZJF-71 were also tested. The highest level of
      glutathione was obtained in 32 h at 30 degrees C and 200 r/min, when 30 mL of
      culture in 250- mL shake flasks was incubated in fermentation medium which
      contained (w/v): 6% cane sugar, 1% peptone, 1% yeast extract, and 2mmol/L
      cysteine. Glutathione yield under the optimal fermentation condition showed a 2.8
      fold improvement over that of the initial condition. The fusant ZJF-71 is stable
      in genetic by analysis of genetic stability.

PMID- 16276879
TI  - [The product identification study on the isolating process of strains produced
      trehalose].
AB  - In the isolating process of stains whose endocellular enzymes can produce
      trehalose on starch or maltooligosaccharides, we discovered the components of
      enzymatic reactant were complicated and it was difficult to purify them each
      other, however, we have to know quickly whether there was tehalose in the
      enzymatic reactant above. In order to make it clearly, thinner layer
      chromatography, high performance liquid chromatography-electrospray ionization
      mass spectrometry and 13C-nuclear magnetic resonance were adopted. The unknown
      oligosaccharide produced by Arthrobacter nicotinovorus D-97 was identified
      rapidly and this unknown oligosaccharide needn't be purified from the enzymatic
      reactant solely. The production on starch or maltooligosaccharides by
      endocellular enzymes of Arthrobacter nicotinovorus D-97 is trehalose. This
      research method in our paper can be applied in the isolating process of
      production trehalose and other functional glucobioses strains.

PMID- 16276880
TI  - [Effects of phytohormones on growth and DHA production by Thraustochytrium
      roseum].
AB  - In this paper, effects of phytohormones on growth and DHA production by
      Thraustochytrium roseum MF2 were studied. Results showed that phytohormones had
      significant affect on growth and DHA production by T. roseum MF2. GA could
      promote the synthesis of DHA, and BA could accelerate the growth of T. roseum
      MF2, so the combination of GA and BA could increase DHA yield. The maximum DHA
      yield of 982mg/L was observed with 2mg/L GA and 3mg/L BA in medium.

PMID- 16276881
TI  - [Detection and identification of phytoplasma strain associated with periwinkle
      yellows].
AB  - A 1.2kb and 1.3kb DNA fragments were amplified in DNA samples extracted from
      periwinkle exhibiting yellows naturally. The amplified fragments were cloned,
      sequenced and compared with other phytoplasma strains. The results showed that
      the 16S rDNA and ribosomal protein gene of periwinkle yellows phytoplasma consist
      of 1239bp and 1244bp, respectively. They all shared high homology (higher than
      97.5%) with phytoplasma strains of 16S rI group. Thus, the result made it clear
      that the phytoplasma strain of periwinkle yellows (PY) is one of the members of
      phytoplasma 16SrI group.

PMID- 16276882
TI  - [Comparative genomics of genes contributed to DNA repair in the radiation
      resistant Deinococcus radiodurans].

PMID- 16276883
TI  - [Interaction between insecticidal crystal proteins and DNA molecule from Bacillus
      thuringiensis].

PMID- 16276884
TI  - [Fungal endophyte-Epichloe and its secondary metabolites].

PMID- 16276885
TI  - [Application of biolog system in the study of microbial community].

PMID- 16276886
TI  - [Review and prospect to the division of microbiology in NSFC].

PMID- 16276887
TI  - [Identification, cloning and sequencing of GST gene of bacterium degrading poly
      aromatic hydrocarbons].
AB  - A bacterium (designated strain ZX4) able to degrade poly aromatic hydrocarbons
      was isolated from oil-contaminated soil. Based on analysis of the 16S rDNA
      sequence, whole cell fatty acid, and Biolog-GN, the strain was identified as
      Sphingomonas paucimobilis. The detection of GST (Glutathione S-transferase)
      indicated that the GST from the strain had the activity of conjugating with CDNB
      and it maybe relate with degradation of PAHs. The PCR product of GST gene from
      the strain confirmed its presence. Phylogeny analysis based on gst sequence
      indicated that the strain was relatively close with the strain which can degrade
      PAH likewise.

PMID- 16276888
TI  - [Genetic diversity analysis of the S10 gene of field and vaccine strains of
      Bluetongue virus].
AB  - S10 gene sequences of 1 attenuated vaccine strain and 31 Chinese field isolates &
      1 South Africa strain of BTV were determined. The results revealed that all 33
      S10 gene segments have 822 nucleotides in length with two in-frame initiation
      codons (nucleotides 20 to 22 and 59 to 61) and a common termination codon
      (nucleotides 707 to 709), which encodes two proteins (NS3 and NS3A). Nucleotide
      difference in the sequence of all S10 gene were from zero to 107 bp (86.4% - 100%
      identity). NS3/NS3A protein showed a light difference from zero to 10 amino acid
      (95.6% - 100% identity). Phylogenetic analysis of the S10 gene of above strains
      sequenced and 9 other strains from GenBank, segregated the Chinese viruses into a
      monophyletic group distinct from US viruses; Nucleotide identity was 85% between
      China Group and US group. The various Chinese isolates segregated into two
      phyletic subgroups based on S10 gene sequences. The clustering of viruses was
      dependent of geographical origin, and independent of host species of isolation,
      serotype & year of isolation.

PMID- 16276889
TI  - [Genetic mutations of heamagglutinin genes of H9N2 subtype influenza A viruses in
      the field in a five-year period].
AB  - Infection in chicken flocks on a farm, where AI outbreak took place in 1998, was
      monitored in a four-year consecutive period and 22 H9N2 subtype viruses were
      isolated. The HA gene and antigenicity of 9 strains among isolates were compared
      with that of isolate of 1998. The results indicated that mutations of HA genes of
      H9 subtype influenza A viruses were observed during five years. However these
      mutations of HA genes didn't lead to sufficient antigenic variation to change the
      cross-protective pattern of these strains. These findings may be fruitful for
      making further study of genetic mutations of AIVs in the field and improving the
      control strategies.

PMID- 16276890
TI  - [Cloning and expression of the mutant 14alpha-demethylase containing the
      alteration of H310D in Candida albicans and the preliminary study on its
      functions].
AB  - The method of recombinant PCR was employed to obtain H310D mutation in 14alpha
      demethylase in Candida albicans). The expression vector pYCYPS1M harboning the
      mutant CYP1M gene was constructed. The mutant CYPS1 was expressed in Sacchromyces
      cerevisiae induced by 2% galactose. At last the MICs of yeasts to Fluconazole
      were determined by broth microdilution testing. Expressed protein was 15% of the
      total microsome proteins. The MICs of yeasts expressed the mutant CYP51 were 4
      fold as that of the yeasts expressed the wild CYP51. The increase of the MICs was
      due to the alteration H310D in CYP51. It could be concluded that the residue of
      H310 was important to the function of CYPS1.

PMID- 16276891
TI  - [Cloning and expressing of 1,3-propanediol oxidoreductase-encoding gene].
AB  - Based on what mentioned above, the gene encoding 1,3-propanediol Oxidoreductase
      (dhaT) in Clostridium pasteurianum CpN-86 was cloned by using PCR method. The
      sequence, expressing vector construction and its expression of dhaT in E. coli
      were accomplished respectively. The recombination protein expressed by dhaT was
      also isolated and purified. The experimental results showed that: (1) The
      homogeneity of dhaT cloned by PCR and that in klebsiella pneumoniae strain was
      82.9%; (2)The enzymatic activity of the protein expressed by cloned dhaT was 108
      microM/ mg; (3)The molecular weight of the protein was 43 kD; (4) The protein
      expressed by dhaT has the same antigenicity as the natural protein of CpN-86
      through Western blotting.

PMID- 16276892
TI  - [Construction, genetic stability and protective efficacy of recombinant fowlpox
      virus expressing hemagglutinin gene of H5N1 subtype avian influenza virus].
AB  - Construction, genetic stability and protective efficacy of a recombinant fowlpox
      virus expressing hemagglutinin (HA) gene (rFPV-HA) of H5 subtype avian influenza
      virus were conducted. The results indicated that the recombinant fowlpox virus
      was obtained and purified by blue plaque selection. HA expressed by rFPV-HA was
      identified by indirect immunofluorescence array. The rFPV-HA could express
      reporter gene LacZ and HA gene after fifteen successive passages in chicken
      embryo fibroblast. The rFPV-HA induced completely protection of chickens against
      lethal challenge with homologous avian influenza virus. The results show that
      rFPV-HA has good genetic stability and antigenicity and should be a useful tool
      in HPAI control program by preventing illness and death in chickens when the
      disease spreads widely.

PMID- 16276893
TI  - [Influence of HBV gene immunization by introduction of nuclear localization
      signal into eukaryonized T7 expression system].
AB  - To investigate the effects of nuclear localization signal on immune response
      induced by eukaryonized T7 expression system. Nuclear localization signal (NLS)
      coding sequence was introduced into eukaryonized T7 expression system containing
      HBV M protein coding gene. Naked gene immunization was performed. The results
      showed that the expression efficiency of T7 system which containing nuclear
      localization signal in vitro was lower than that without NLS. In vivo study found
      that HBV specific immune response induced by NLS lacking eukaryonized T7 system
      was significantly higher than that in eukaryonized T7 expression system
      containing NLS. HBV specific Th1 and Th2 type immune responses were also observed
      in the mice immunized with T7-HBsAg plasmid lacking NLS, indicating that the
      nuclear localization signal might not be essential in T7 expression system.

PMID- 16276894
TI  - [Mutagenesis of ion beam implantation and identification of two new rifampicin
      resistance determining sites in rpoB gene in Escherichia coli].
AB  - The rifampicin resistance mutations induced by low energy nitrogen ion
      implantation had been investigated in this study referred to the study of 60Co
      gamma ray irradiation. It is suggested that low energy nitrogen ion beam
      implantation might generate a lower damage but get higher mutation rates than
      60Co-gamma ray irradiation did. The frequencies showed the preference of base
      substitutions induced by N+ ion beam are CG--> TA transition, GC-->AT transition,
      AT--> GC transition and AT-->TA transversion which occupy 87.5% (77/88) of the
      total mutation of base substitutions. Two new rif-determining sites had also been
      identified in rpoB gene in Escherichia coli. The first new site located in 1551.
      When dG1551 was replaced by dC, it resulted in Gln517 was substituted by a
      histidine. The other new site located in 1692. When dC1692 was replaced by dT, it
      resulted in a Pro564 is changed into a leucine. The synonymous mutation of the
      second site had been reported but the nucleotide substitution, dC-->dT, had not
      been identified before.

PMID- 16276895
TI  - [Study on gene knockout using red system in Shigella flexneri].
AB  - The technology of gene knockout using lambda Red system in bacteria has been
      developed lately, but its application being limited to Esherichia coli. In order
      to get some experiences in other bacteria we select four genes, including alkA,
      wcaJ, yphF and dam, to test gene knockout using Red system in E. coli and
      Shigella. As a result, three genes were successfully knocked out in E. coli
      except dam while only alkA gene was knocked out in Shigella. It showed that the
      Red system should be improved if it was to be effectively used in Shigella and
      other bacteria.

PMID- 16276896
TI  - [Importance of five genes presented in Xenorhabdus nematophilus BP toxin gene
      cluster to its insecticidal activity].
AB  - Importance of five genes, named as xptA1, xptD1, xptB1, xptC1 and xptA2 presented
      in the toxin gene cluster of X. nematophilus BP strain, to its insecticidal
      activity against the neonate of Helicorvepa armigera was examined. This was
      achieved by analyzing and comparing the presence or absence of these five genes
      in and the insecticidal activity of each of the five clones screened from genomic
      cosmid library of X. nematophilus BP by in situ hybridization and another three
      subclones constructed from the enzyme-digested plasmid DNA of one of the
      insecticidal cosmid clones. The insecticidal activity of the clone or subclone
      was estimated by the 50% lethal concentration (LC50) of the neonate of H.
      armigera feed with the mixture of artificial diet and the cells of the clone or
      subclone examined. The presence or absence of each of the five genes in the clone
      or subclone was determined by the results of PCR amplification of the whole or
      the two ends of the targeted gene. The results indicated that: 1 the presence of
      xptC1 and xptA2 was critical for the full insecticidal activity of the toxin gene
      cluster while absence of xptD1 and/or xptA1 had little effect on the insecticidal
      activity against the neonate of H. armigera; 2. mixing cosmid clone XnBP76 and
      subclone Sub20k, which had a gene structure of (xptA1+, xptD1+, xptB1+, xptC1+
      and xptA2-) and (xptA1-, xptD1-, xptB1-, xptC1- and xptA2+), respectively, did
      not achieve the full insecticidal activity. The functions of these five genes in
      the insecticidal process were discussed briefly.

PMID- 16276897
TI  - [Purification and characterization of a novel alginate lyase from marine Vibrio
      sp. QY102].
AB  - A marine bacterium Vibrio sp. QY102 with high alginate-degrading activity was
      isolated from surface of sargassum. The alginate lyase recovered from culture
      supernatant was purified to electrophoretic homogeneity by a procedure of 0.22
      microm membrane filtration, DEAE-sepharose ion-exchange and Superdex75 gel
      filtration chromatography. The molecular mass of the enzyme determined by SDS
      PAGE was 28.5kD. The optimum pH and temperature for enzyme activity were pH 7.1
      and 40 degrees C, respectively. The enzyme was stable from pH 5 to 10 and at
      temperature below 40 degrees C. Ca2+ and Mg2+ enhanced the enzyme activity,
      whereas Ni2+, Al3+, Zn2+ and Ba2+ inhibited the activity, and the lyase activity
      was strongly inhibited by SDS and EDTA. The activity of the alginate lyase
      purified in this experiment was obviously higher than that of others reported so
      far, and this enzyme showed a preference for polymannuronic acid in substrate
      specificity.

PMID- 16276898
TI  - [Purification and some properties of bacteriolytic enzyme R1 from Streptomyces
      griseus RX-17].
AB  - Bacteriolytic enzyme R1 was purified to electrophoretic homogeneity with the
      recovery of 6.89% activity by ammonium sulfate precipitation, CM-Sephadex C - 50,
      CM-Sepharose Fast Flow and Sephadex G-75 chromatography from the culture
      supernatant of Streptomyces griseus RX-17. The molecular weight and PI of R1 were
      16.8 kD and 9.10. The optimal temperature and pH for R1 against Streptococcus
      mutans Ingbritt were 70 degrees C and 6.6, respectively. Below 50 degrees C and
      at range pH 6 - 10, R1 was stable. While treated at 60 degrees C for 1 hour, the
      residual activity was only about 20.3%. Zn2+, Cu2+, Fe2+, Cd2+ and Pb2+ could
      completely inactivate the enzyme. Chelating agents, hydroxylamine hydrochloriae,
      Monoiodoacetic acid inhibited the lytic activity against Streptococcus mutans
      Ingbritt, whereas Mg2+, 2-Mercaptoethanol and some surfactants could stimulate
      the activity. The enzyme had a broad bacteriolytic spectrum against many G+, G-
      bacteria which were resistant to egg-white lysozyme. Especially high activity was
      shown on Streptococcus mutans, Staphylococcus aureus and Lactobaillus.

PMID- 16276899
TI  - [Chitosanase production in convoluted fibrous bed bioreactor with two-step
      process].
AB  - Chitosanase activity can be increased remarkably by a two-step process, in which,
      the growth of T. reesei was in the first step with glucose as carbon source and
      enzyme induction by D-glucosamine in the second step. With the novel process
      chitosanase activity produced was about 100% higher than that in the traditional
      one step process. Under the optimized culture conditions: aeration rate was
      4L/min (2 vvm) and age of mycelia were 72 h, The activity of chitosanase produced
      by immobilized T. reesei in convoluted fibrous bed bioreactor(CFBB) was 246mU/mL
      which was about 39% higher than that with free cell culture in 5L CSTR under the
      same culture conditions. Furthermore, the novel bioreactor was also feasible to
      be operated in repeated batch mode. During 10 repeated-batch in 15 days, the
      average production of chitosanase activity to each batch was kept 235mU/mL.

PMID- 16276900
TI  - [Characterization of Amycolatopsis meditteranei U32 chromosome by pulse-field gel
      electrophoresis].
AB  - Amycolatopsis meditteranei U32 is an industrial strain with high yield of
      rifamycin SV. Its chromosome structure was characterized by pulse-field gel
      electrophoresis. The topological structure of U32 chromosome was linear and its
      genome size was about 10 Mb. There was no internal plasmid found. Gene encoding
      several enzymes involved in rifamycin bio-synthesis and relevant primary
      metabolism as well as protein related to metabolic regulation were localized by
      Southern blot. The results revealed that there were at least five copies of rrn
      operon in U32. The rifamycin bio-synthesis gene cluster was located on one about
      700 kb PshBI fragement where several other important genes related to primary and
      secondary metabolism were also situated. They were the nasD gene, the mcm gene
      encoding methylmalonyl CoA mutase, the accA gene encoding acethyl CoA carboxylase
      biotin carrier protein and one copy of the rrn operons.

PMID- 16276901
TI  - [Study on the process of degrading filter paper cellulose by Sporocytophaga sp.
      JL-01].
AB  - Sporocytophaga is a kind of bacteria that can glide on the solid medium surface.
      It can decompose the cotton and filter paper after 6 days cultured. The
      sporocytophaga can only produce a low extracellular carboxymethylcellulase
      activity and no other cellulase activities. In this work, the process about
      degradation of filter paper fibre by a strain of Sporocytophaga was studied using
      scan electronmicroscopy. The morphological changes that Sporocytophaga sp. JI-01
      grew on filter paper were observed. The study revealed the JL-01 adhered tightly
      to the surface of filter paper fibre or penetrated into interior of the fibre
      through its 2.5 microm - 4.0 microm bacilliform cells in the process of
      degrading. The bacilliform cells degrade the cellulose strongly and produced a
      mass of sticky polysaccharides. At the anaphase of cultured, the bacteria existed
      as a cycloidal dormancy body-sporocyst.

PMID- 16276902
TI  - [Evaluation for enhanced aphidicidal activity of a noval emulsifiable formulation
      of Beauveria bassiana conidia].
AB  - A noval emulsifiable formulation (EF) of Beauveria bassiana SG8702 containing
      10(10) conidia/mL was prepared by suspending dry conidia in mineral oil-based
      liquid containing emulsifier, stabilizer and UV protectant (emulsion), and then
      bioassayed on newly merged adults of the green peach aphid, Myzus percisae, in
      parallel to the unformulated conidia (UC). For inoculation, five gradient
      concentrations of aqueous EF and UC suspensions (5 x 10(5) - 1 x 10(8)
      conidia/mL) were separately sprayed on to aphids on detached cabbage leaves (30 -
      40 adults/leaf) using a Micro Ulva hand-held sprayer, generating EF dosages of
      1.5, 6.3, 32.6, 87.6 and 701.1 conidia/mm2, and UC dosages of 2.8, 9.2, 52.7,
      114.8 and 1005.9 conidia/mm2, respectively. All dosage treatments including
      controls for EF (100-fold dilution of the emulsion) and UC (water spray) were
      replicated three times (aphid colonies on three leaves), and maintained in Petri
      dishes at 23 degrees C and 12 : 12 (L: D) for 8-day daily records. Cadavers,
      whenever found, were moved into a moist chamber to facilitate fungal outgrowths
      for verification of B. bassiana infection. The resulting data fit very well to
      time-dose-mortality model with EF having a larger dose effect (1.05 +/- 0.10)
      than UC (0.82 +/- 0.11) and also faster time effect. The estimates of the dose-
      and time-effect parameters were then used to compute lethal concentrations (LC50)
      and time lengths (LT50). The estimates of LC50 with 95% confidence intervals for
      both EF and UC were 9.0 (6.9 - 11.6) and 634 (263 - 1532) conidia/mm2 on day 4
      after spray, and 3.3 (2.4 - 4.6) and 5.3 (3.2 - 8.6) on day 7, apparently
      decreasing with increasing time lengths after spray. The estimates of LT50 for EF
      and UC were 4.9 d and 7.2 d at 5 conidia/mm2, 4.0 d and 5.6 d at 10 conidia/mm2,
      and 3.2 d and 4.5 d at 100 conidia/mm2, indicating a trend of decrease with
      increasing counts of conidia attached to the leaves. The results indicate that
      the emulsifiable formulation of B. bassiana conidia had greater aphidicidal
      activity than the unformulated conidia. Finally, problems with evaluation of
      mycoinsecticides and other microbial formulations are discussed and technical
      standards are recommended.

PMID- 16276903
TI  - [Ca2+ signaling pathways associated with the invasion of Streptococcus pneumoniae
      to type II pneumocytes].
AB  - Labelled F-actin with FITC-phalloidin, we observed F-actin rearrangements by
      Streptococcus pneumoniae adhesion of type II pneumocytes (A549). Invasion of S.
      pneumoniae to A549 cells was determined by pretreating A549 cells with
      cytochalasin D. To investigate whether F-actin rearrangements can be blocked by
      Ca2+ inhibitors, A549 cells were pretreated with Ca2+ inhibitors datrollene. A549
      cells were loaded with Fura-2/AM to determine the concentration of cytosolic free
      calcium by S. pneumoniae adhesion of A549 cells after 30,60,90 minutes
      respectively. Intact S. pneumoniae can promote F-actin rearrangements.
      Cytochalasin D is able to prevent S. pneumoniae invasion of A49 cells. S.
      pneumoniae adhesion of A549 cells increased cytosolic free calcium after 30, 60,
      90 minuts. Ca2+ inhibitors datrollene block F-actin rearrangements dose
      dependently. It suggested S. pneumoniae can provoke F-actin rearrangements
      through Ca2+ signaling pathways, which will further lead to S. pneumoniae
      invasion of A49 cells.

PMID- 16276904
TI  - [Purification and activities of an alkaline protein from mushroom Coprinus
      comatus].
AB  - An Alkaline protein, y3, can be purified from the fruiting bodies of mushroom
      Coprinus comatus by means of CM-sepharose FF ion-exchange column chromatography
      and Superdex 75 High Resolution molecular sieve chromatography. The protein has a
      molecular weight of about 14.4kD by SDS-PAGA. Some activities of y3 have been
      detected, and the result is the following: the inhibition rate against Tobacco
      Mosaic Virus is 83.0% when the concentration of y3 is 12.5 microg/ mL. y3 is able
      to agglutinate rabbit and human erythrocytes at the concentration of 1.562
      microg/mL and 0.781 microg/mL. Using an assay system based on mach cancer cell
      line MGC-803, y3 was studied for its inhibitory ability against celles
      multiplication, and the IC50 is 12 microg/mL. The N-terminal sequence is
      NRDVAACARFIDDFCDTLTP, which has no homology with other sequences in Genbank.

PMID- 16276905
TI  - [Production of polyhydroxyalkanoates by a mixed culture].
AB  - The feasibility of using a mixed culture of A. chroococcum G-3 and B. megaterium
      G-6 in the production of polyhydroxyalkanoates has been studied. The optimal
      conditions for the mixed culture were established. After the G-3 strain was
      incubated alone for 24 - 28 hours, the broth was inoculated with 15% (v/v) of the
      G-6 culture. 0.5% peptone and 0.5% NH4NO3 were added to the mixture. The mixed
      culture was proceed to 42 - 46 h. Final dry cell weight was up to 32 g/L and the
      content of PHA was up to 80%. Combined with the nutrient supplement, the dry cell
      weight increased to 53 g/L and the content of PHA increased to 42g/L. The
      conversion of sucrose to PHA is 0.32. The mixed culture solved the problems
      caused by the increase in viscosity, poor mass transfer, low supplemental sucrose
      amounts.

PMID- 16276906
TI  - [MGAP-A microbe genome annotation platform].
AB  - A Microbe Genome Annotation Platform (MGAP) was developed and applied to the
      cynobacterium PCC7002 genome annotation. Various bioinformatics software tools
      from sequence analysis to gene identification and function prediction were
      implemented in MGAP. Protein sequence databases SWISSPROT and PDBseq, protein
      information resource InterPro and COG were also integrated in the platform. The
      web interface of MGAP has the functionality to display a circular map of gene
      distribution and GC contents throughout the genome. Detailed information such as
      the DNA and protein sequence, the location of genes on chromosomes can be viewed
      by clicking the corresponding object within the map. MGAP is based on a PC/Linux
      system affordable for small biological laboratories and has the advantage of
      using free software tools including MySQL, Apache and Perl.

PMID- 16276907
TI  - [Synthesis of copolyesters consisting of 3-hydroxybutyrate and 3-hydroxyhexanoate
      by Aeromonas hydrophila WQ and its molecular basis].
AB  - Aeromonas hydrophila WQ isolated from lake water was found to be able to
      synthesize polyhydroxyalkanoates (PHA) copolymer consisting of 3-hydroxybutyrate
      (HB) and 3-hydroxyhexanoate (HHx) (PHBHHx). Lauric acid was found to be the most
      suitable carbon source for cell growth and PHBHHx accumulation. The bacteria
      accumulated 49% PHBHHx containing 6% HHx in terms of cell dry weight when grown
      on lauric acid for 72 h. 42% PHBHHx consisting of 14% HHx was obtained with 5 g/L
      glucose and 10 g/L lauric acid as co-substrate. Higher glucose concentration
      greatly reduced the cell concentration and PHA content. The PHA biosynthesis
      genes from A. hydrophila WQ was successfully cloned using a two-step PCR cloning
      strategy based on PHA biosynthesis genes organization of Aeromonas caviae. A.
      hydrophila WQ and A. caviae shared high identities in the PHA gene loci, namely,
      ORF1, phaC and phaJ had 100%, 97% and 97.5% identities respectively. PHA
      synthases of A. caviae and A. hydrophila were proposed to contain type IV PHA
      synthases which are different compared with type I PHA synthases on the substrate
      specificity and location arrangement of PHA metabolic genes.

PMID- 16276908
TI  - [Production of a novel heparinase from Sphingobacterium sp].
AB  - The novel heparinase-producing bacterial strain Sphingobacterium sp. was isolated
      and screened from soil. The optimum medium composition is (g/L): Soytone 20, NaCl
      1, K2HPO4 2.5, MgSO4 0.5, Heparin 2, Sucrose 15, pH 7.5. The optimum temperature
      for growth and enzyme production was 32 degrees C. When cultured at a rotating
      shaker at 30 degrees C for 36 hours, 200 r/min, 50 mL medium in 500 mL flask, the
      production of heparinase reached 4000 U/L.

PMID- 16276909
TI  - [Invasion of Aeromonas hydrophila in cells involving signal transduction and
      cytoskeleton].
AB  - Invasion of Aeromonas hydrophila strain Ah J-1 isolated from diseased fish to
      cultured HEp-2cells monolayer was evaluated by the recovery of gentamincin
      resistant (Gm') bacteria from Triton X-100 cell lysates. The invasive efficiency
      (IE) could reach to 0.2% at 37 degrees C. In addition, potential signal
      transduction pathways that precede bacterial internalization were studied by
      using signal transduction inhibitors. Bacterial internalization of Ah J-1
      involved microfilaments and protein tyrosine kinase since cytochalasin D (an
      inhibitor of microfilament polymerization) and genistein (an inhibitor of protein
      tyrosine kinase) prevented internalization. Staurosporine (a protein kinase C
      inhibitor) and Sodium orthovanadate (a protein tyrosine phosphatase inhibitor)
      accelerated internalization of Ah J-1 into HEp-2 cells.

PMID- 16276910
TI  - [Genes involved in biosynthesis and metabolism of trehalose and their use in
      biotechnology].

PMID- 16276911
TI  - [Archaeal diversity of Zabuye Lake in Tibet analyzed by culture-independent
      approach].
AB  - With culture-independent approach, microbial DNA was directly extracted from
      samples of Zabuye saline soda lake. Using the microbial DNA as template, archaeal
      16S rDNAs were amplified by PCR. Amplified products were cloned and sequenced. 60
      different cloned partial sequences, most of which were related to
      haloalkaliphilic archaeon, were acquired. In the phylogenetic tree, some clones
      of Zabuye lake belonged to Genus Natronobacterium, Natrinema, Natronococcus,
      Natronorubrum, Natronomonas, Halorubrum, Haloterrigena, Halorhabdus in Family
      Halobacteriaceae. Other clones represent some novel groups. All of them show
      prolific archaeal diversity of Zabuye lake.

PMID- 16276912
TI  - [Analysis of RAPD fingerprinting in Exserohilum monoceras strains].
AB  - Exserohilium monoseras is a potential agent for barnyardgrass (Echinochlao crus
      galli) control. This study was to evaluate the genetic diversity of this fungus
      with 17 strains isolated from different rice growing regions of China by the
      random amplified polymorphic DNA (RAPD). Among 25 arbitrary primers, 20 primers
      could get enough amplified bands for all the strains. A total 239 products were
      amplified. Polymorphic bands were 95.8% of the total products. The 17 strains
      could be identified based on RAPD fingerprinting established in this study.
      Genetic distance calculation and cluster analysis resulted in great genetic
      variation among the strains. The genetic similarity was related with the
      morphology and the pathogenicity of the strains. The results showed that RAPD
      maker could be applied in the utilization and the identification of weed pathogen
      resources.

PMID- 16276913
TI  - [Cloning and expression of ICP cry1AB16 gene of Bacillus thuringiensis].
AB  - With two pairs of primers designed on the basis of the sequence of cry1 and
      cry1Ab gene from Bacillus thuringiensis (Bt), a novel insecticidal crystal
      protein crylAb gene of Bt was amplified from bacillus strain AC-11 by using Long
      Template PCR System. Southernblot further confirmed that the novel gene existed
      in plasmid of the strain. The amplified fragment was sequenced and compared with
      cry1Ab1 gene in EMBL/GenBank. The results showed that eight nucleotides and seven
      amino acid residues were different from that of cry1Ab1, suggesting that it was a
      new crylAb gene, which was designated cry1Ab16 in GenBank (Accession No.
      AF375608). The cry1Ab16 gene was cloned into the E. coli expression vector pQE30,
      creating the recombinant plasmid pQCT, which was then transformed into E. coli
      M15. Westernblot analysis showed that Cry1Ab16 protein, induced by IPTG was
      expressed in the strain M15 (pQCT) with the molecular mass of approximate 130 kD,
      but Cry1Ab16 was unstable and was mostly degraded into about 65 kD protein.
      Bioassay showed that the LC50 of Cry1Ab16 against the third instar lavae of
      Plutella xylostella with a spreaded method was 258.3 mg/L, and it could also
      inhibit the growth of Spodoptera larvae.

PMID- 16276914
TI  - [Cloning of beta-tubulin gene from Gibberella zeae and analysis its relationship
      with carbendazim-resistance].
AB  - Whole beta-tubulin genes from wild carbendazim(MBC)-sensitive isolate, field MBC
      resistant isolate and induced MBC-resistant mutant of Gibberella zeae were cloned
      and sequenced with 3 pairs of primers. These genes have 1631bp length, including
      3 introns, encoding 447 amino acid. The homology of amino acid tubulin gene of G.
      zeae with that of other common plant pathogenic filamentous fungi is from 95.12%
      approximately 99.30%. Sequence comparison among MBCs, field MBCR and induced MBCR
      isolates revealed there was no mutation, even one. So it can be concluded that
      the mechanism of MBC-resistance to G. zeae is different from other filamentous
      fungi caused by point mutation at amino acid position 198 or other position of
      beta-tubulin gene.

PMID- 16276915
TI  - [Cloning and expression of Yersinia pestis V antigen in Escherichia coli BL21
      (DE3)].
AB  - The structure gene of V antigen was amplified from the wild strain of Yersinia
      pestis by means of PCR, and was cloned into vector pET-42b (+). Then, V antigen
      was successfully expressed in E. coli BL21(DE3) with the induction of IPTG. The
      expressing amount of the aim protein is as high as 32.8 percent of the total
      bacterial protein.

PMID- 16276916
TI  - [Genetic characterization of the entire genome of an H9N2 avian influenza virus
      A/Chicken/Shanghai/F/98].
AB  - Eight full-length genes of an H9N2 subtype avian influenza virus
      A/Chicken/Shanghai/F/ 98(H9N2), were amplified by RT-PCR and rapid amplification
      of cDNA ends (RACE) and sequenced. The results of phylogenetic analysis showed
      that A/Chicken/Shanghai/F/98 was entirely different from Quail/Hong Kong/G1/97
      which was directly related to human infection with avian influenza virus in Hong
      Kong, whereas its HA, NA, M and NS genes belonged to A/Chicken/Beijing/ 1/94-like
      sublineage with the nucleotide homology of 96.7%, 96.4%, 97.5% and 98.0%
      respectively. The homology of NA gene between A/Chicken/Shanghai/F/98 and
      A/Duck/Hong Kong/Y280/ 97 was 97.4% and they both lost 9 nucleotides between nt
      205 to 206. However, the PB2, PB1, PA, NP genes did not show any close
      relationship with those of the three known sublineages and the later three didn't
      share immediate ancestors with available isolates whose sequences had been
      reported. Therefore, A/Chicken/Shanghai/F/98 is a product of natural reassortment
      between H9N2 avian influenza viruses from different sublineages.

PMID- 16276917
TI  - [cDNA cloning and expression in Escherichia coli of rice black-streaked dwarf
      virus segment 7].
AB  - Using primers designed from the terminal sequences of maize rough dwarf virus S6,
      a 2.2 kb cDNA fragment was amplified by RT-PCR from maize plants showing maize
      rough dwarf disease. Sequence analysis shows that the full length of this cDNA is
      2193bp. It contains two open reading frames that encoded two polypeptides with
      molecular weight of 41.0kD and 36.3kD, respectively. Results of multi-sequences
      alignment suggest that, this cDNA sequence has significant similarity to rice
      black-streaked dwarf virus S7, much higher than to MRDV S6. The ORFs were cloned
      into expression vectors, pET21-d (ORF1) or pGEX-KG (ORF2), respectively, and then
      transformed to BL21(DE3)-gold. After induction with IPTG, both proteins were
      highly expressed. The recombinant proteins were purified and high titer antisera
      of these two proteins were prepared.

PMID- 16276918
TI  - [Study on high-expression of soluble hbFGF in Escherichia coli].
AB  - The formation of inclusion body is correlated with the overexpression of foreign
      proteins in Escherichia coli. Controlling of the expression level seems to be
      critical to increase the soluble component. With the prerequisite of no
      alterations in amino acid sequence, the wobble bases of the first 3 codons
      downstream the initiation codon ATG of a hbFGF high-expression mutation,
      established previously, were changed into the bases of the native hbFGF
      sequences. Seven primers were synthesized for retro-mutations, after PCR were
      undertaken, the products were cloned into pET-3c, and recombinants were
      transformed into BL21 (DE3) plysS for expression. One strain with high solubility
      and bioactivity were identified, indicating that restriction of the expression
      level of recombinant protein is helpful for high-solubility.

PMID- 16276919
TI  - [Study on the properties of methyl parathion hydrolase from Pseudomonas sp. WBC
      3].
AB  - A methyl parathion degradation enzyme, or methyl parathion hydrolase (MPH, EC
      3.1.8.1), locating in the soluble intracellular fraction of Pseudomonas sp. WBC
      3, was purified 49.1-fold to homogeneity by one-step ion exchange chromatography.
      The physical and chemical properties of the purified MPH were studied. The
      purified MPH displayed relatively broad optimal temperature around 40 degrees.
      The activity of MPH was affected by pH and the optimal pH was 11.0. Cd2+ and Fe2+
      could enhance the catalytic efficiency of MPH while Hg2+, Zn2+, Al3+ and Bi3+
      showed inhibition effect. With methyl parathion as the optimal substrate, the Km
      was 0.0807mmol/L and the kcat was 2.1 x 10(6) min(-1). In addition, the
      comparison of native and subunit molecular weights of MPH suggested that this
      enzyme was a monomer of approximate 34kD.

PMID- 16276920
TI  - [Selection of acetate-tolerant mutants from Escherichia coli DH5alpha and the
      metabolic properties of mutant DA19].
AB  - Esherichia coli DH5alpha is one of the widely used host strains in genetic
      engineering. However, foreign gene expression level in this strain is seriously
      inhibited due to its great sensitivity to the accumulated metabolite, acetate.
      This study aimed at improving the tolerance of this strain against acetate. Cells
      of E. coli DH5alpha were irradiated with 60Co, and subsequently continuous
      culture of the irradiated cells was conducted with gradual increase in the
      dilution rate and the selective pressure, acetate concentration in the medium.
      The mutants were picked up on MA plates which contained 5g/L sodium acetate. 5
      strains with great improvement in acetate tolerance were obtained, among which
      DA19 was the best. In cultivation of DA19 in complex media YPS and YPS2G, the
      cell density, maximum specific growth rate and acetate produced were respectively
      1.17 and 1.05, 1.08 and 1.27, and 0.06 and 0.59 times of those of DH5alpha. In a
      chemically defined medium, the cell density of DA19 was 3.4-fold of that of
      DH5alpha. The cell density of DA19 in a medium containing 10g/L sodium acetate
      was comparable to that of DH5alpha in the same medium without the addition of
      acetate.

PMID- 16276921
TI  - [Study on xylose fermentation by Neurospora crassa].
AB  - The influence of oxygen limitation and medium initial pH on xylose fermentation
      by Neurospora crassa AS 3.1602 was investigated. N. crassa AS 3.1602 has high
      ability of xylose fermentation producing ethanol and xylitol. Oxygen limitation
      has big influence on ethanol and xylitol production. The maximum conversion rate
      of ethanol was 63.2% obtained under semi-aerobic conditions. The maximum
      conversion rate of xylitol was 31.8% obtained under micro-aerobic conditions.
      Xylitol accumulation is behind the accumulation of ethanol. The optimal pH is 5.0
      for ethanol fermentation, and 4.0 for xylitol fermentation, respectively. Xylose
      fermentation is greatly inhibited at high pH. The yields of ethanol and xylitol
      are greatly influenced by the initial concentration of xylose. The addition of
      glucose inhibits both the xylose utilization and the ethanol and xylitol
      production.

PMID- 16276922
TI  - [Metabolic flux analysis of L-Tryptophan biosynthesis].
AB  - The metabolic flux balance model of L-Try synthesis by Corynebacterium glutamicum
      was constructed in this paper. Using this model, the metabolic flux distribution
      during the middle and late period were determined and the optimal flux
      distribution were calculated by linear program of MATLAB software. The analysis
      results indicate that 24.85% metabolic flux entered the HMP pathway and 75.15%
      entered the EMP cycle. But comparing to the optimal flux distributions, the
      production of L-Try should be improved from the genetic manipulation and
      fermentation control through reducing byproduct of amino acid and decreasing the
      metabolic flux of TCA and EMP.

PMID- 16276923
TI  - [The secondary metabolites research of the alkalophlic strain YIMGQ14 tracked by
      the TLC assay].
AB  - In the course of the microbial resources exploitation, the secondary metabolites
      research of the alkalophilic strain YIMGQ-14 was carried on using the TLC method
      and with the coordinate of the TLC database searching. Two patented biological
      active compounds "Umycin C" and "Umycin B" were isolated and purified. The result
      showed that, compared with the ordinary biological screening, the TLC screening
      is fast, convenient, economical and much more suitable for the small scale daily
      screening purpose. With the reconstruction and supplement of the related TLC
      data, the working efficiency of this method can be improved greatly.

PMID- 16276924
TI  - [Study on the rejuvenating by isolation and the immobilization of Thiobacillus
      ferrooxidans].
AB  - A strain of Thiobacillus ferrooxidation T1 with stronger oxidation ability and
      more exuberant vitality was isolated from the liquid with regressive Thiobacillus
      ferrooxidans by method of dilution butteron on plate. A fixed-bed bioreactor was
      constructed by immobilized cells of Thiobacillus ferrooxidans with H-2 carriers.
      In the state of bioreactor operation, a maximum Fe2+ oxidation rate of
      7.67g[Fe2+] x h(-1) x L(-1) was attained. We studied the precipitates formed on
      the surface of the carriers during the operation of the bioreactor. By X-ray
      diffraction analyses we proved the precipitates were jarosite.

PMID- 16276925
TI  - [Study on PVA-alginate co-immobilization of Xanthomonas ampelina TS206].
AB  - Ice nucleation activity and anti-leaking capability are both important technical
      parameters in INA (Ice nucleation active bactetia) bacteria immobilization which
      can be adopted on freezing concentrate. Both PVA and alginate are good medium for
      immobilization. They can be used on co-immobilization of ice nucleation-active
      bacteria (Xanthomonas ampelinaTS206). The results showed that quantity of
      embedding affects ice nucleation activity greatly. The order of importance to
      comprehensive scores of technical standard should be concentration of Sodium
      alginate > Boric acid > PVA > CaCl2. The optimized concentration are PVA 8%,
      sodium alginate 1%, CaCl2 1.1% and boric acid 5%. A conclusion can be draw that
      ice nucleation activity increases with the number of beads and shows little
      pertinency with the time of immobilization, whereas anti-leaking capability can
      be influenced faintly by the number of beads and the time of immobilization.

PMID- 16276926
TI  - [Effects of Aeromonas hydrophila biofilm on the drug resistance].
AB  - Aeromonas hydrophila (Ah) biofilm (BF) model in vitro was established and
      antibiotic effects of 11 antimicrobials on BF and free-cell(FC) bacteria were
      tested. After the Ah J-1 on the surfaces of the silicon pieces was incubated for
      7 days in TSB, the intact BF was formed by detection of AgNO3 solution staining.
      The FC bacteria were resistant to Penicillin but susceptible to Enrofloxacin and
      Fulgram. Their minimum bactericidal concentrations (MBCs) were 256 microg/mL,
      0.03 microg/mL and 0.25 microg/mL respectively. Florfenicol had a strong
      antibacterial effect on BF bacteria and the ratio of MBC between BF and FC
      bacteria was 2 to 1, but more than 32 to 1 occurred for Kanamycin, Penicillin and
      Neomycin. Morphology and structure of BFs with/without the treatment of
      Enrofloxacin were observed under scanning electron microscope, while the
      bactericidal curve was detected. Enrofloxacin could eradicate the FC bacteria
      completely but not the BF bacteria at a concentration of 4 fold MBC. The 32 fold
      MBC Enrofloxacin could entirely kill the FC bacteria in 4h, but in 24h for BF
      bacteria. The result suggested that BF enabled Ah to have strong resistance to
      antimicrobials and the potential influence of BF should be highly considered.

PMID- 16276927
TI  - [Development of bacterial community in faeces of weaning piglets as revealed by
      denaturing gradient gel electrophoresis].
AB  - PCR and denaturing gradient gel electrophoresis (DGGE) were used to monitor the
      development of bacterial community in faeces of 12 weaning piglets. The regions
      V6 to V8 of the 16S rDNA of faecal bacteria were amplified. DGGE profiles of the
      PCR amplicons were compared by similarity analysis. Results revealed simple DGGE
      profiles for faecal samples from piglets on the first day of weaning and piglets
      from the same sow showed similar DGGE profiles. After weaning as the piglets grew
      DGGE profiles became complicated and diverse. Each individual piglet had its
      unique DGGE profile, with low similarity between piglets. The source of sow and
      the diet showed no apparent effect on the DGGE profiles. For the piglets fed a
      diet containing oliogofructose, DGGE similarity analysis showed bacterial
      community in the faeces developed fast during the first week and relatively slow
      later after weaning.

PMID- 16276928
TI  - [Screening for the peptides blocking cholera phage VP1 transfection to host cell
      by phage random amino acid peptide library].
AB  - Use Vibrio cholerae El Tor Typing Phage VP1 as ligand to screen phage-display
      random 7 amino acid peptide library, ELISA and inactivation experiment were used
      to identify positive clone. The ratio of output to input was increased after
      three rounds of screening. Pseudo-positive was decreased stepwise. It indicated
      the efficient enrichment. After three rounds of screening, 312 out of 360 phage
      clones were positive in ELISA, 1 clone shows blocking VP1 adsorbs to Vibrio
      cholerae by inactivation experiment. Sequencing result indicate that amino acid
      sequences are p245: LeuGlnGlnLysHisLeuLeu; p40, p55: GlnLeuIleMetIleArgHis; p69,
      p274 IleThrProArgAsnArgSer. Getting some peptides can mimick the VP1 receptor
      epitopes, one peptide can block VP1 transfection to host cell, it was a clue to
      study receptor's structure and phage infectious mechanism to host cell.

PMID- 16276929
TI  - [Study on submerged culture conditions of lipase inhibitor producing strain].
AB  - The optimum medium and fermentations conditions of the lipase inhibitor producing
      strain Bacillus sp. LF were studied. The optimal medium was selected after single
      factor test and orthogonal test as follows: lactose 0.8%, peptone 1%, (NH4)2SO4
      0.8%, NaCl 0.5%, original pH 7.2. With 4% (V/V) inoculum in 40 mL medium in 250
      mL flask, Bacillus sp. LF could reach high yield of lipase inhibitor after 24 h
      at 30 degrees C. The highest lipase inhibitory activity in broth could reach
      52.3%.

PMID- 16276930
TI  - [Effects of extracts of Chinese medicines on Ganoderma lucidum in submerged
      culture].
AB  - Effects of water and ethanol extracts of 10 Chinese medicines, such as Astragalus
      membranaceus, Coix lachryma-jobi, etc., on biomass and exopolysaccharide of
      Ganoderma lucidum were studied by submerged culture. The results showed: water
      extracts of all medicines can improve the culture of G. lucidum except of A.
      membranaceus, ethanol extracts of C. lachryma-jobi, Dioscorea opposita,
      Codonopsis pilosula, and Achyranthes bidentata( < 187.5g Medicine/L substrate)
      can also increase the biomass of G. lucidum, but the ethanol extracts of Angelica
      sinensis, Dendrobium nobile check the growth of G. lucidum. The production of
      exopolysa-ccharide can be improved by all the Chinese medicines and their dosage
      used in this experiment, Although A. sinensis, D. Nobile check the growth of G.
      lucidum, they could stimulate the secretion of exopolysaccharide in lower dosage.
      It is concluded that some Chinese medicines, such as C. lachryma-jobi, D.
      opposita, C. pilosula, etc. can be processed by the fermentation of G. lucidum,
      and bio-active compound can be produced by adding appropriate Chinese medicine in
      the substrate to culture G. lucidum.

PMID- 16276931
TI  - [Preparation of chiral alcohol by stereoselective reduction of acetophenone and
      chloroacetophenone with yeast cells].
AB  - Four strains of microorganisms which have activity of chloroacetophenone
      reduction were screened, in which Saccharomyces cerevisiae B5 showed the highest
      activity and good stereoselectivity. This strains showed different activity on
      the reduction of various substrates in the following order: 2'-chloroacetophenone
      > 2-chloromethylacetophenone > 4'-chloroacetophenone > 3'-chloroacetophenone >
      acetophenone. Ethanol is the best cosubstrate and its optimal concentration is
      5%.

PMID- 16276932
TI  - [Taxonomy of entomopathogenic nematophilic bacteria].

PMID- 16276933
TI  - [Recent research and prospect on taxol and its producing fungi].

PMID- 16276934
TI  - Training of oral health personnel in Fiji.

PMID- 16276935
TI  - Comparative analysis of oral health indicators among young children in Hawai'i,
      the Republic of Palau and Territory of Guam, 1999-2000.
AB  - Dental caries prevalence data were collected in Hawai'i, Palau and Guam and
      analyzed for dft, DMFT, unmet treatment needs, sealant utilization and various
      caries patterns. Data sets include examinations of 24,752 children ages 5 through
      9 years of age in Hawai'i, 558 children in Palau and 1,518 children in Guam.
      Dental disease in early childhood is truly endemic throughout the Pacific basin.
      The findings of this report quantify in a standardized manner and contrast, basic
      oral health / oral disease indicators from each jurisdiction. While children from
      all three jurisdictions demonstrated dental disease prevalence rates which far
      exceed those found on the U.S. mainland, overall, children in Guam were found to
      be the poorest oral health indicators, followed by Palau and Hawai'i. Overall,
      young children at all sites exhibited excessively high caries prevalence and
      unmet treatment needs rates. Significant progress has been made at Palau in the
      past decade, however, at all three sites presented, more work is necessary if
      early childhood caries is to be brought under control. Findings also include an
      apparent negative correlation between dental sealants and DMFT rates.

PMID- 16276936
TI  - Infant and child feeding practices and dental caries in 6 to 36 months old
      children in Fiji.
AB  - Dental caries is a multifactorial disease. These factors include the presence of
      cariogenic micro-organisms, fermentable carbohydrates in diet, susceptible tooth
      and time. Diet appears to strongly affect caries development. The aim of this
      study was to examine the feeding practices of infants and pre-school children in
      the Central Division of the Fiji Islands and suggest appropriate preventive
      dental strategies. A sample of 102 children aged 6-36 months was randomly
      selected. Information on feeding practices and oral hygiene habits was obtained
      through a self-administered questionnaire completed by parents from the post
      natal clinics. Children were categorized into age groups of 6-12, 13-24 and 25-36
      months. Most of the children (55.5%) were bottle fed in the 6-12 months age group
      and 44.5% were breast-fed. However percentage of children being breast-fed
      decreased markedly increased with age. Most of them were breast-fed at some
      stage. The children who were bottle-fed increased in the 13-24 months age group
      but decreased in 25-36 months group. Snacks were given between meals for most of
      the children. Sugar was used as the common sweetener among bottle-fed children.
      Parents are definitely in need of appropriate advice on feeding and oral hygiene
      practices. An oral health education programme needs to be mounted at post-natal
      clinics.

PMID- 16276937
TI  - Early childhood caries among Hawaii public school children, 1989 vs. 1999.
AB  - Utilizing a standardized oral health assessment tool, public school children ages
      5 through 9 were evaluated Statewide in 1989 and 1999. In both samples, it was
      demonstrated that Asian & Pacific Islander children (as a group), by contrast
      with Caucasian, African Amercan or Hispanic children, suffered from
      disproportionately high rates of dental caries, were more likely to have unmet
      treatment needs and less likely to utilize dental sealants. Significant variance
      among oral health/ oral disease indicators was found among ethnic and regional
      groups and all Hawaii cohorts were found to have poorer oral health indicators by
      contrast with U.S. national findings. Data was not found to follow any particular
      pattern with regards to urban vs. rural settings. This report shows the value of
      considering a variety of oral health indicators in evaluating the health of a
      community. More research needs to be done in evaluating the influence of
      socioeconomic status and cultural beliefs and practices on the oral health of
      young children in Hawai'i.

PMID- 16276938
TI  - Tooth brushing and utilization of dental services in Fiji (1998).
AB  - Utilization of services is considered the presence or absence of care received.
      The most common measure of utilization is the annual number of dental visits per
      person. This study aims to determine oral health practices, which were a measure
      of their oral hygiene status and the use of health care facilities. It also aims
      to investigate the major problems that exist within the health care system in
      1998, which may explain the lack of use of dental services. Fijians and Indo
      Fijians were two ethnic groups in the sample, selected by stratified multi-stage
      cluster sampling. Only two age categories, 15-19 and 35-44 year-olds were
      selected being the index age for World Health Organization in Oral Health
      Surveys. A total of 1,000 questionaires were distributed and the completed
      questionnaires (n = 619) were collected immediately. Thirty one percent of the
      respondents indicated that they learnt to care for their teeth from dental
      personnel. Of the individuals who brushed their teeth twice a day, 41% visited
      the dentist within the last 12 months. Majority of the individuals (65%) who
      brushed their teeth twice or more daily indicated that they needed dental
      treatment. Individuals who visited the dentist within the last 12 months reported
      having a tooth extracted (53%), check-up (29%), filling (8.9%), polishing of
      teeth (3.7%), gum problem (3.2%) and false teeth (1.8%). Individuals who brushed
      twice daily did not visit the dentist within the last 12 months because nothing
      was wrong (63.2%), too busy (9%) and afraid of the dentist (7%). More than 80% of
      the respondents were satisfied with the current services, but indicated
      improvement on the waiting time (31.2%), availability of more treatment options
      in dental clinics (27.5%), dental fees (15.4%), improvement on the facilities for
      dental care (10.1%), a customer-friendly dental personnel (9.4%) and
      considerations for infection control (6.4%).

PMID- 16276939
TI  - Oral health status of older adults in Fiji: 1985-1999.
AB  - This paper examines the oral health status of older adults in Fiji to determine
      the risks of dental disabilities. Using cross-sectional data collected in 1985
      and 1999, logistic regression models are used to measure the effect of select
      demographic, socioeconomic and health variables on difficulty with chewing. While
      the general picture for the older persons is quite positive, the largest concern
      is the striking increase in poverty as a predictor for our dependent variable.

PMID- 16276940
TI  - Oral health status and treatment needs of institutionalized elderly and
      disadvantaged population in Fiji (1997).
AB  - Information on the oral health of institutionalized elderly populations in a
      number of countries is available but, no data is available nor published on the
      elderly population of Fiji. A pilot survey was carried out at the nursing homes
      in the Suva area. The aim of this study was to investigate the dental status and
      treatment needs of institutionalized elderly people. Examiner was calibrated and
      consent approved from the relevant institutions. This study found that residents
      were institutionalized, because family members could not care for them; did not
      receive any form of financial assistance and therefore totally relied on the
      institution; generally had medical problems such as neurological disorders,
      cardiovascular disease and diabetes. Generally had poor oral health status such
      as root stumps, many missing teeth, calculus and shallow pockets were common,
      oral hygiene practices were poor, high demand for dentures/or the dentures were
      not clean, some cases of leukoplakia were found and there was an urgent need for
      the dental profession to deliver dental care. Recommendations include issues in
      developing a supporting environment, provision of adequate and appropriate
      access, community education and skill development, workforce development and
      research in geriatric dentistry in Fiji.

PMID- 16276941
TI  - Smoking and chewing habits of oral cancer patients in the Solomon Islands.
AB  - A 5-year retrospective study (1994-97 and 1999) on the prevalence of oral cancer
      was conducted using patients' records at the Dental Department in the Solomon
      Islands, National Referral Hospital. The aim of the study was to investigate the
      relationship between smoking and betel nut chewing in patients with oral cancer.
      Relevant information regarding patient's smoking and betel nut chewing, site of
      oral cancer and personal history were extracted from patient's dental records and
      analyzed. There were 48 cases of oral cancer reported at the hospital over the 5
      year period. Males aged 45 years and over were mostly affected with the
      distribution showing 31.5% of the cases from Malaita, 20.8% from Temotu and 14.6%
      from the Western Provinces. Ninety percent (90%) of the oral cancer patients
      practice both smoking and betel nut chewing, compared to those who only practice
      one habit and this was highly significant (p<0.001). Chewing of high levels of
      betel quid per day (>5) showed statistical significance (p<0.001) for oral cancer
      patients (83%) compared to those individuals (17%) who chewed lesser (<5) betel
      quid. About 62% of these patients smoked cigarette rolls and tobacco stick rolls.
      However, there was no significance in the relationship of oral cancer and those
      individuals who smoke (p > 0.05). Buccal mucosa (3 1 %) and buccal
      mucosa+adjacent comer of the mouth (25%) are the most common affected site in the
      oral cavity. This study has shown that the combinations of tobacco smoking and
      chewing of betel quid are the main risk factors for oral cancer. Therefore, these
      factors are to be emphasized in the public and preventive education of
      communities in the Solomon Islands.

PMID- 16276942
TI  - Quantitative evaluation of variance in secondary dentition eruption among ethnic
      groups in Hawai'i.
AB  - Though little scientific evidence existed to support the belief among dentists
      who treat Pacific Islander populations that many children of the region erupt
      secondary teeth earlier and at an eruption rate which exceeds Caucasian children.
      Based upon a data set created in Hawai'i during the 1998-1999 school year, of
      26,097 public school children, the opportunity presented itself to examine for
      variance in eruption timing and sequence. Hawai'i is an ethnic diverse community,
      with a majority population comprised of Asians and Pacific Islanders. Children, 5
      through 9 years of age, were examined for gender and ethnic variance. In the
      aggregate, at all ages, girls erupted teeth earlier than boys, however, while
      generally true among individual tooth types, that variance was not always
      statistically significant. By ethnic group, African Americans exhibited earlier
      eruption by contrast with Caucasians, however, Caucasian children caught up by
      nine years of age. Native Hawaiian, Samoan and Tongan children exhibited earlier
      and high rates of secondary dentition eruption than Caucasian or African American
      children. Children of various Asian cohorts did not exhibit significant variance
      by contrast with Caucasians. Based upon these findings, the authors recommend
      that dietary fluoride supplementation of Native Hawaiian, Samoan and Tongan
      children begin at birth rather than 6 months of age and that these children be
      targeted for pit & fissure sealants as early as five years of age.

PMID- 16276943
TI  - Effects of a propofol--ketamine admixture in human volunteers.
AB  - As the ideal sedative does not exist for all situations, particularly in settings
      with limited resources, the effect of a propofol-ketamine combination in human
      volunteers was examined. Eleven American Society of Anesthesiologists (ASA)
      physical status I volunteers were administered propofol at a loading dose of 1
      mg/kg and two minutes later by 0.7 mg/kg of ketamine. This was followed by a
      propofol-ketamine combination of 5 mg/kg of propofol admixed with 0.7 mg/kg of
      ketamine that was infused over one hour via a 60 gtts/ml intravenous. Infusion
      set. Cardiorespiratory parameters were recorded and blood samples taken to
      measure plasma catecholamine levels prior to, during and for thirty minutes
      following the termination of the infusion. Rate of respiration and oxygen
      saturation levels did not alter significantly from baseline levels. When there
      was a cardiovascular decrease from base line levels it was on average 11% for
      systolic, 15% diastolic blood pressure and 14% for heart rate. Only plasma
      adrenaline and noradrenaline increased by 28 and 20%, 10 minutes following the
      bolus injectons. No dysphoria was experienced. This combined sedoanalgesic
      technique in nonstimulated human volunteers maintains spontaneous ventilation and
      may be considered as abalanced alternative to traditional conscious sedation or
      general anesthesia.

PMID- 16276944
TI  - Oral melanosis: a case report of Peutz-Jegher's Syndrome in Suva, Fiji.
AB  - This paper reports on a case of oral melanosis resultng from Peutz-Jeghers
      Syndrome, a hereditary disease characterized by harmatomatous polyposis and by
      mucocutaneous melanic pigmentation, in a 14-year-old Fijian girl with a family
      history of the disease. The patient underwent surgery for treatment of an
      intestinal obstruction due to a small intestine intussusception. Recognition of
      the characteristic pigmentation by dentists may lead to early diagnosis of
      associated harmatomatous polyps or neoplastic disease that may be life
      threatening.

PMID- 16276945
TI  - Sacrococcygeal teratoma: a case report and a review of literature.
AB  - Sacrococcygeal teratoma is a congenital tumour, which may present in the prenatal
      period or at birth. The case presented illustrated one of the complications of
      sacrococcygeal teratoma, which is tumour rupture at birth. Other complications
      include fetal hydrops, fetal hydronephrosis, cervical dystocia, bleeding and
      death. Currently, diagnosis of sacrococcygeal teratoma is made during the
      prenatal period using modern imaging technique. The diagnostic technique of
      choice is ultrasonography. Early diagnosis influences clinical decision and
      management, which produces, better outcome.

PMID- 16276946
TI  - Dental caries in South Pacific populations: a review.
AB  - Dental caries (tooth decay) was uncommon in Pacific Island communities before
      European trading and migration expanded into the Region. The etiology of this
      oral microbial disease is a consequence of changed diets, food preparation and
      lifestyle. In particular, the easy availability of a high level of frequent
      dietary supplementation with refined sucrose (sugar) and carbohydrates is the key
      factor in the etiology of tooth decay. While tooth decay initially developed as a
      health problem in the more accessible Pacific islands over a century ago, it has
      spread increasingly as trading, travel and cash economies have developed to
      include even the more geographically remote communities. In this review selected
      epidemiological data are presented to show the magnitude, variation and secular
      changes in the prevalence of tooth decay in different communities. Tooth decay in
      conjunction with the historically endemic adult gum diseases poses a major public
      health problem in terms of pain, premature loss of teeth and the need for oral
      rehabilitation. Implementation and monitoring of caries control programs is a
      priority need in most communities. It is impractical to consider a return to
      indigenous diets and lifestyles as a strategy for caries prevention. Instead
      promotion of proven modern community preventive programmes, notably appropriate
      use of fluorides, 'fissure sealants' together with control of excessive
      consumption of diets rich in refined sugar is required if a significant increase
      in the levels of tooth decay is to be avoided.

PMID- 16276947
TI  - Periodontal health in South Pacific populations: a review.
AB  - Periodontal (or gum) disease is historically endemic in all indigenous
      communities in the South Pacific Region. While the disease becomes evident in
      mature adults the pathology becomes overt by adolescence or earlier. The initial
      gum inflammation progresses increasingly with age and may lead to pathological
      destruction of the tooth supporting tissues, tooth loosening and potential tooth
      loss. For most adults the disease presents as an adult-onset generalized chronic
      marginal-gingivitis-periodontitis-calculus complex. Microbiological components of
      dental plaque on tooth surfaces and dental calculus initiate the pathology. While
      the general clinical features are similar between adults and between communities,
      epidemiological studies have identified variations in disease progression. Also
      severity of the disease may be influenced by systemic health factors such as
      diabetes, known to be common in the Region. A common outcome, loss of teeth,
      usually becomes evident from the fourth decade onwards. Once established the
      plaque- gingivitis- calculus- periodontitis complex becomes increasingly
      difficult to reverse. Early adoption and maintenance of routine oral care actions
      through family, social, community and educational actions will improve long-term
      oral health, tooth loss, potentially adverse systemic health and in general
      better lifestyles.

PMID- 16276948
TI  - Cancer of the oral cavity- a growing concern in the Micronesia: a case report
      from the Marshall Islands.
AB  - Cancer of the oral cavity is of growing concern worldwide. In the Micronesia,
      there has been a recent increase in use of betel nut and tobacco chewing in
      addition to already existing problem of smoking and alcohol drinking. These
      deleterious habits have further added the risk for development of oral cancers in
      the Marshall Islands. The oral cancers have good prognosis, which is directly
      related to the early diagnosis and treatment. Advanced staged cancers need
      mutilating surgery in addition to radiotherapy and carry high mortality rate. The
      epidemiology, etiology and recent approaches in the management of oral cavity
      cancer has been discussed along with a case report of advanced cancer of the
      floor of the mouth from the Marshall Islands.

PMID- 16276949
TI  - Oral implications of diabetes mellitus.
AB  - The importance of diabetes care in the dental practice is only as important as
      the dentist wants it to be. Practicing dental professionals must prepare
      themselves for the increase in the diabetic patient population and the extensive
      medical care that they require to curtail the development of complications.
      Dentist's training in preventive healthcare philosophy makes them aptly suited to
      play a significant role as part of the "Diabetes Team."

PMID- 16276950
TI  - Consent in dentistry.
AB  - This article aims to provide fundamental information regarding consent when
      providing dental care and a review of the current literature. The change in
      attitude of patients with emphasis on being involved and informed of every aspect
      of care is not only apparent in adults but also when providing care for children
      and young adults. It is important for dentists to be well informed of the
      fundamental process of consent, which exist under the law (affecting both adults
      and minors) in order to provide care within the legal framework.

PMID- 16276951
TI  - The early childhood caries prevention program in Palau.
AB  - Early Childhood Caries is a significant public health problem in Palau. Data have
      shown that nearly 80% of children ages 3-5 years of age in Palau experience
      dental caries and a significant number of these children require general
      anesthesia to treat or remove painful or infected carious teeth. In response to
      this growing problem, the Division of Oral Health has systematically developed a
      prevention program in collaboration with the Maternal and Child Health Unit under
      the Ministry of Health. The core program involves integrating preventive oral
      health services into all regular prenatal and postnatal care programs and
      improving the capacities of health professionals to provide such services. The
      program promotes the idea that oral health is an important component to overall
      health and all efforts are made to integrate oral health into broader public
      health initiatives. Both health and process outcomes are being monitored by an
      oral health surveillance system, while preliminary data show improved oral health
      among young children. This paper takes a closer look at the development of the
      Palau program.

PMID- 16276952
TI  - Pacific oral health summit--"A call for action", 2001.

PMID- 16276953
TI  - Infections in long-term-care facilities: screen or clean?

PMID- 16276954
TI  - A norovirus outbreak at a long-term-care facility: the role of environmental
      surface contamination.
AB  - BACKGROUND: The role of environmental surface contamination in the propagation of
      norovirus outbreaks is unclear. An outbreak of acute gastroenteritis was reported
      among residents of a 240-bed veterans long-term-care facility. OBJECTIVES: To
      identify the likely mode of transmission, to characterize risk factors for
      illness, and to evaluate for environmental contamination in this norovirus
      outbreak. METHODS: An outbreak investigation was conducted to identify risk
      factors for illness among residents and employees. Stool and vomitus samples were
      tested for norovirus by reverse transcription polymerase chain reaction (RT-PCR).
      Fourteen days after outbreak detection, ongoing cases among the residents
      prompted environmental surface testing for norovirus by RT-PCR. RESULTS: One
      hundred twenty-seven (52%) of 246 residents and 84 (46%) of 181 surveyed
      employees had gastroenteritis. Case-residents did not differ from non-case
      residents by comorbidities, diet, room type, or level of mobility. Index cases
      were among the nursing staff. Eight of 11 resident stool or vomitus samples
      tested positive for genogroup II norovirus. The all-cause mortality rate during
      the month of the outbreak peak was significantly higher than the expected rate.
      Environmental surface swabs from case-resident rooms, a dining room table, and an
      elevator button used only by employees were positive for norovirus. Environmental
      and clinical norovirus sequences were identical. CONCLUSION: Extensive
      contamination of environmental surfaces may play a role in prolonged norovirus
      outbreaks and should be addressed in control interventions.

PMID- 16276955
TI  - Survey of long-term-care facilities in Iowa for policies and practices regarding
      residents with methicillin-resistant Staphylococcus aureus or vancomycin
      resistant enterococci.
AB  - OBJECTIVES: To identify infection control policies and practices used by long
      term-care facilities (LTCFs) in Iowa for residents with methicillin-resistant
      Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE), and to
      estimate the prevalence of residents known to have these organisms. DESIGN:
      Survey. SETTING: LTCFs in Iowa from December 2002 through March 2003. RESULTS: Of
      the 429 LTCFs in Iowa, 331 (77%) responded to the survey. The estimated
      prevalence of residents known to have MRSA was 13.4 per 1,000 and that of
      residents known to have VRE was 2.3 per 1,000. Facilities owned by the government
      or those with an average of more than 86 occupied beds were more likely to have
      residents known to have MRSA and VRE (P = .002 and .007, respectively). Of the
      responding facilities, 7.3% acknowledged that they refused to accept individuals
      known to have MRSA and 16.9% acknowledged that they refused to accept those known
      to have VRE. Facilities in large communities (population, > 100,000) were least
      likely to deny admission to an individual known to have either MRSA or VRE (P =
      .05). Most facilities reported adhering to the national guidelines, but fewer
      than half (44.7%) of the respondents had heard of the Iowa Antibiotic Resistance
      Task Force's guidelines regarding residents with MRSA or VRE. CONCLUSIONS: Many
      LTCFs in Iowa care for residents known to have MRSA or VRE, but some refuse to
      admit these individuals. Infection control personnel and public health officials
      should work together to educate LTCF staff so that residents receive proper care
      and resistant organisms do not spread within this setting.

PMID- 16276956
TI  - Characteristics that promote transmission of Staphylococcus aureus nursing homes
      in German nursing homes.
AB  - OBJECTIVE: To determine factors that influence transmission of Staphylococcus
      aureus in nursing homes in the Rhine-Neckar region of southern Germany. DESIGN:
      Ecologic study. SETTING: Forty-seven nursing homes in the region. PARTICIPANTS:
      Residents of the approached nursing homes who agreed to participate. METHODS:
      Personal data and swabs of the nares were collected from participants. Swabs were
      examined for growth of S. aureus. All S. aureus isolates were typed using pulsed
      field gel electrophoresis (PFGE). Transmission rates were calculated by dividing
      the number of transmissions (ie, cases in which two inhabitants shared the same
      PFGE type) by the number of S. aureus carriers. Characteristics of the nursing
      homes were correlated with a home's transmission rate. RESULTS: In each nursing
      home, 12% to 54% of the residents were colonized with S. aureus. The transmission
      rates for the 47 nursing homes ranged from 0% to 70%. A linear regression model
      revealed that a stay in the nursing home of longer than 6 months and
      accommodation in a room with 3 or more beds were positively associated with the
      transmission rate. Receipt of antibiotics during the 4 weeks preceding the study
      was negatively associated with transmission. CONCLUSIONS: Stays beyond 6 months
      and accommodation in rooms with multiple beds are important for the transmission
      of S. aureus. One way to reduce transmission would be to design facilities with
      single and double rooms. However, the social needs of the residents must be
      evaluated and respected.

PMID- 16276957
TI  - Patterns and predictors of inpatient falls and fall-related injuries in a large
      academic hospital.
AB  - OBJECTIVES: Most research on hospital falls has focused on predictors of falling,
      whereas less is known about predictors of serious fall-related injury. Our
      objectives were to characterize inpatients who fall and to determine predictors
      of serious fall-related injury. METHODS: We performed a retrospective
      observational study of 1,082 patients who fell (1,235 falls) during January 2001
      to June 2002 at an urban academic hospital. Multivariate analysis of potential
      risk factors for serious fall-related injury (vs no or minor injury) included in
      the hospital's adverse event reporting database was conducted with logistic
      regression to calculate adjusted odds ratios (aORs) with 95% confidence intervals
      (CI95) RESULTS: The median age of patients who fell was 62 years (interquartile
      range, 49-77 years), 50% were women, and 20% were confused. The hospital fall
      rate was 3.1 falls per 1,000 patient-days, which varied by service from 0.86
      (women and infants) to 6.36 (oncology). Some (6.1%) of the falls resulted in
      serious injury, ranging by service from 3.1% (women and infants) to 10.9%
      (psychiatry). The most common serious fall-related injuries were bleeding or
      laceration (53.6%), fracture or dislocation (15.9%), and hematoma or contusion
      (13%). Patients 75 years or older (aOR, 3.2; CI95, 1.3-8.1) and those on the
      geriatric psychiatry floor (aOR, 2.8; CI95, 1.3-6.0) were more likely to sustain
      serious fall-related injuries. CONCLUSIONS: There is considerable variation in
      fall rates and fall-related injury percentages by service. More detailed studies
      should be conducted by floor or service to identify predictors of serious fall
      related injury so that targeted interventions can be developed to reduce them.

PMID- 16276958
TI  - Healthcare-associated myiasis: prevention and intervention.
AB  - Healthcare-associated myiasis (maggot infestation) can have complications that go
      well beyond the medical consequences of the infestation for patients, their
      families, and facilities. Prevention of healthcare-associated myiasis requires
      effort on two fronts: minimizing patient risk factors and reducing fly
      populations in the healthcare environment. If myiasis occurs, intervention must
      be swift, thorough, and interdisciplinary. The first priority always is the well
      being of the patient. Preservation and identification of the maggots can help
      determine the likely timing and circumstances that led to the infestation.
      Conditions favoring the infestation must be identified and then corrected. Free
      and rapid communication must be promoted. A single designated knowledgeable
      spokesperson to communicate with the patient, employees, and, as needed, the
      media will reduce miscommunication and hasten mitigation. Following the
      guidelines presented in this document, healthcare facilities should be able to
      reduce the likelihood of healthcare-associated myiasis and effectively intervene
      when such events occur.

PMID- 16276959
TI  - Nursing home-acquired bloodstream infection.
AB  - OBJECTIVES: This article reviews published studies of nursing home-acquired BSI
      in North America to determine whether there have been changes in the epidemiology
      of this infection in the past 20 years and to define indications for blood
      cultures in the nursing home setting. METHODS: A Medline search was conducted for
      the period from 1980 to August 2003. RESULTS: Seven studies of nursing home
      acquired BSI were identified. The incidence of nursing home-acquired BSI was low
      (0.3 episode per 1,000 resident care-days). Sources of BSI changed little during
      the past two decades, with urinary tract infection representing approximately 50%
      of the episodes. The bacteriology also did not change substantially during the
      past 20 years; gram-negative bacilli were isolated in approximately 50% of the
      episodes and Escherichia coli was the most commonly isolated organism. In the
      most recent study, covering the period 1997-2000, resistance to fluoroquinolones
      and broad-spectrum penicillins and cephalosporins was uncommon among gram
      negative blood isolates; MRSA was the most common resistant organism causing
      nursing home-acquired BSI. Case-fatality rates changed little during the past 20
      years; urinary tract infection was associated with the lowest mortality and
      pneumonia had the highest case-fatality rate. CONCLUSION: There has been little
      change in the epidemiology of nursing home-acquired BSI in the past 20 years.
      Given the low incidence of BSI and the low overall yield of positive results of
      blood cultures (probably < or = 6%), there is currently no support for the
      routine use of blood cultures in the nursing home setting.

PMID- 16276960
TI  - Clinical and epidemiologic features of methicillin-resistant Staphylococcus
      aureus in elderly hospitalized patients.
AB  - We describe characteristics of elderly patients with MRSA identified in 37
      Canadian hospitals between 1995 and 2002. Of these inpatients, 6,613 (66%) were
      older than 65 years. They were more likely than younger patients to have been
      colonized without infection and to have had MRSA isolated from urine or the
      perineum. The epidemiology and clinical features of these patients is distinct
      from that of younger patients.

PMID- 16276961
TI  - Lessons learned from a norovirus outbreak in a locked pediatric inpatient
      psychiatric unit.
AB  - We report an outbreak of norovirus in a locked pediatric inpatient psychiatric
      unit with attack rates of 75% among 4 patients and 26% among 38 staff. Factors
      contributing to the outbreak included environmental contamination, close staff
      patient contact including sharing meals, and inability to confine the index
      patient with the use of contact precautions.

PMID- 16276962
TI  - Synthesis and antiviral activity of novel anomeric branched carbocyclic
      nucleosides.
AB  - Novel anomeric branched carbocyclic nucleosides were synthesized from 1,3
      dihydroxy acetone. 4'-Hydroxymethyl was installed by [3,3]-sigmatropic
      rearrangement reaction and 1'-methyl group was introduced by carbonyl addition of
      methylmagnesium bromide. The coupling of nucleosidic bases and desilylation
      afforded a series of novel nucleosides. The synthesized compounds 16-19 were
      evaluated for their antiviral activity against HIV-1, HSV-1, HSV-2, and EMCV.
      Compounds 16 and 19 exhibit toxicity non-related to any anti-HIV-1 activity.

PMID- 16276963
TI  - Synthesis of 5-aminolevulinic acid (ALA) and its t-butyl ester for the
      fluorescence detection of early cancer.
AB  - 5-Aminolevulinic acid and its derivatives, which are known to affect the early
      diagnosis and treatment of cancer, have been synthesized. Simple methods for the
      synthesis of 5-aminolevulinic acid (ALA), a precursor of porphyrins, have been
      developed in our laboratory for use in studies on the biosynthesis of porphyrins.

PMID- 16276964
TI  - Effects of hydroxyl group numbers on the B-ring of 5,7-dihydroxyflavones on the
      differential inhibition of human CYP 1A and CYP1B1 enzymes.
AB  - Flavonoids are polyphenols composed of two aromatic rings (A, B) and a
      heterocyclic ring (C). In order to determine the effects of the number of
      hydroxyl groups in the B-ring of the flavonoids on human cytochrome P450 (CYP) 1
      family enzymes, we evaluated the inhibition of CYP1A-dependent 7-ethoxyresorufin
      omicron-deethylation activity by chrysin, apigenin and luteolin, using bacterial
      membranes that co-express human CYP1A1, CYP1A2, or CYP1B1 with human NADPH
      cytochrome P450 reductase. Chrysin, which possesses no hydroxyl groups in its B
      ring, exhibited the most pronounced inhibitory effects on CYP1A2-dependent EROD
      activity, followed by apigenin and luteolin. On the contrary, CYP1A1-mediated
      EROD activity was most potently inhibited by luteolin, which is characterized by
      two hydroxyl groups in its B-ring, followed by apigenin and chrysin. However, all
      of the 5,7-dihydroxyflavones were determined to similarly inhibit CYP1B1
      activity. Chrysin, apigenin, and luteolin exhibited a mixed-type mode of
      inhibition with regard to CYP1A2, CYP1B1, and CYP1A1, with apparent Ki values of
      2.4, 0.5, and 2.0 microM, respectively. These findings suggested that the number
      of hydroxyl groups in the B-ring of 5,7-dihydroxyflavone might have some
      influence on the degree to which CYP1A enzymes were inhibited, but not on the
      degree to which CYP1B1 enzymes were inhibited.

PMID- 16276965
TI  - Tungtungmadic acid, a novel antioxidant, from Salicornia herbacea.
AB  - Tungtungmadic acid (3-caffeoyl-4-dihydrocaffeoyl quinic acid) is a new
      chlorogenic acid derivative that was isolated from the Salicornia herbacea. The
      structure of tungtungmadic acid was determined using chemical and spectral
      analysis. The antioxidant activity of tungtungmadic acid was evaluated using
      various antioxidant assays, including free radical scavenging, lipid peroxidation
      and hydroxyl radical-induced DNA strand breaks assays. Tungtungmadic acid (IC50 =
      5.1 microM and 9.3 microM) was found to have higher antioxidant activity in the
      DPPH scavenging assay as well as in the iron-induced liver microsomal lipid
      peroxidation system. In addition, the tungtungmadic acid was also effective in
      protecting the plasmid DNA against strand breakage induced by hydroxyl radicals.

PMID- 16276966
TI  - A phenolic glucoside isolated from Prunus serrulata var. spontanea and its
      peroxynitrite scavenging activity.
AB  - A new phenolic glucoside (1), pursargentoside, was isolated from the leaves of
      Prunus serrulata var. spontanea, along with three other known compounds, orobol 7
      omicron-glucoside (2), 1beta, 2alpha, 3alpha, 24-tetrahydroxy-urs-12-en-28-oic
      acid (3), and chlorogenic acid (4). The structure of pursargentoside (1) was
      identified by spectroscopic data analysis including 1D and 2D NMR spectroscopy,
      as 2-omicron-beta-(6'-benzoyl)-glucopyranosyl omicron-(Z)-coumaric acid.
      Compounds 1, 2, and 4 exhibited ONOO scavenging activity, whereas compound 3 was
      determined to be virtually inactive.

PMID- 16276967
TI  - New cytotoxic benzopyrans from the leaves of Mallotus apelta.
AB  - Two new benzopyrans 6-[1'-oxo-3'(R)-hydroxy-butyl]-5,7-dimethoxy-2,2-dimethyl-2H
      1-benzopyran (1) and 6-[1'-oxo-3'(R)-methoxy-butyl]-5,7-dimethoxy-2,2-dimethyl-2H
      1-benzopyran (2) were isolated from the leaves of Mallotus apelta Muell.-Arg.,
      (Euphorbiaceae). Their chemical structures were elucidated by spectroscopic
      analyses, especially by 1 D-, 2D-NMR and MS spectra. Compound 1 was found to have
      strong cytotoxic effect against two human cancer cell lines as human
      hepatocellular carcinoma (Hep-2, IC50: 0.49 microg/mL) and rhabdosarcoma (RD,
      IC50: 0.54 microg/mL), while compound 2 showed moderate activity against Hep-2
      cell line (IC50, 4.22 microg/mL) by in vitro assay.

PMID- 16276968
TI  - Inhibitory effect on TNF-alpha-induced IL-8 production in the HT29 cell of
      constituents from the leaf and stem of Weigela subsessilis.
AB  - Twelve compounds were isolated from the MeOH extract of the leaf and stem of the
      Korean endemic plant Weigela subsessilis L. H. Bailey. Their chemical structures
      were elucidated on the basis of physicochemical and spectroscopic data and by
      comparison with those of published literatures. These compounds were identified
      as three sterols, beta-sitosterol acetate (2), betasitosterol (3), daucosterol
      (11), eight triterpenoids, squalene (1), ursolic acid (4), ilekudinol A (5),
      corosolic acid (6), ilekudinol B (7), esculentic acid (8), pomolic acid (9),
      asiatic acid (10), and one iridoid glycoside, alboside I (12). This is the first
      report pertaining to the isolation of these compounds from Weigela subsessilis L.
      H. Bailey. In addition, three compounds 7, 9, and 12 were found to display a
      strong inhibitory effect on the production of IL-8 in the HT29 cells stimulated
      by TNF-alpha.

PMID- 16276969
TI  - Cytotoxic sesquiterpene lactones from Saussurea calcicola.
AB  - Seven sesquiterpene lactones were isolated by the chromatographic separation of
      the MeOH extract of the aerial parts of Saussurea calcicola (Compositae). Their
      structures were determined spectroscopically to be cynaropicrin (1), arguerin B
      (2), cebellin F (3), 8alpha-hydroxy-11alpha, 13-dihydrozaluzanin C (4),
      desacylcynaropicrin (5), 3beta-hydroxy-8alpha-epoxymethylacriloiloxy
      4(15),10(14),11(13)-trien-guaian-6,12-olide (6), and kandavanolide (7). Compounds
      1 and 2 showed significant cytotoxicity against five cultured human tumor cell
      lines with ED50 values ranging from 0.23-1.72 microg/mL.

PMID- 16276970
TI  - Antimicrobial constituents from fruits of Ailanthus altissima SWINGLE.
AB  - A new naturally occurring sterol, compound 5, and six known stigmasterols were
      isolated from fruits of Ailanthus altissima Swingle by repeated column
      chromatography and RP-HPLC. Their structures were identified as, 5alpha
      stigmastane-3,6-dione (1), 3beta-hydroxystigmast-5-en-7-one (2), stigmast-5-ene
      3beta, 7alpha-diol (3), 6alpha-hydroxystigmast-4-en-3-one (4), 5alpha-stigmastane
      3beta, 6beta-diol (5), stigmast-4-ene-3beta, 6alpha-diol (6), stigmast-5-ene
      3beta, 7alpha, 20xi-triol (7) by spectral analysis and comparison with the
      published data. These compounds have not been reported from genus Ailanthus,
      whereas compound 7 was identified by NMR for the first time. In addition, the 95%
      ethanol extract and compounds from the fruits of Ailanthus altissima SWINGLE were
      assayed for in vitro antimicrobial activity. The extract was potent active
      against the assayed bacteria while compounds 3 and 7 exhibited moderate activity.

PMID- 16276971
TI  - Inhibition of collagenase by naturally-occurring flavonoids.
AB  - We examined the inhibitory activities of various flavonoids, including the
      flavanones, flavones/isoflavones and flavonols, on collagenase from Clostridium
      histolyticum to establish their therapeutic potential against skin inflammation
      and photoaging. In general, the flavonols were stronger inhibitors than the
      flavones/isoflavones, and this indicated the importance of the C-3 hydroxyl
      substitution. Quercetin was the most active flavonoid among those tested, and it
      showed an IC50 of 286 microM. These novel results suggest that certain
      flavonoids, particularly the flavonols, may prevent collagen breakdown by
      inhibiting collagenase in inflamed skin as well as photoaged skin.

PMID- 16276972
TI  - Iridoid glycosides isolated from Oldenlandia diffusa inhibit LDL-oxidation.
AB  - An iridoid glycoside, oldenlandoside III (5) was isolated from the n-butanol
      fraction of methanol extracts of the aerial parts of Oldenlandia diffusa Roxb.
      along with six others previously characterized iridoid glycosides; geniposidic
      acid (1), scandoside (2), feretoside (3), 10-omicron-benzoylscandoside methyl
      ester (4), asperulosidic acid (6) and deacetylasperulosidic acid (7). Compounds
      1, 2, and 7 inhibited LDL-oxidation, and showed 63.3+/-2.0, 62.2+/-1.6, and
      63.8+/-1.5% inhibition, respectively, at a concentration of 20 microg/mL.

PMID- 16276973
TI  - 11-Methoxyviburtinal, a new iridoid from Valeriana jatamansi.
AB  - Five compounds of iridoids, lignan and phenylpropanoid glycosides were isolated
      from the roots of Valeriana jatamansi by column chromatography. Their structures
      were elucidated as 11-methoxyviburtinal (1), baldrinal (2), prinsepiol-4-omicron
      beta-D-glucoside (3), coniferin (4), and hexacosanic acid (5) by spectroscopic
      analysis. 11-Methoxyviburtinal was a new compound, and others were isolated from
      the plant for the first time.

PMID- 16276974
TI  - Potential effects of microglial activation induced by ginsenoside Rg3 in rat
      primary culture: enhancement of type A Macrophage Scavenger Receptor expression.
AB  - Brain microglia are phagocytic cells that are the major inflammatory response
      cells of the central nervous system and widely held to play important
      pathophysiologic roles in Alzheimer's disease (AD) in both potentially neurotoxic
      responses and potentially beneficial phagocytic responses. In the study, we
      examined whether ginsonoside Rg3, a by-product of red ginseng, enhances the
      microglial phagocytosis of Abeta. We found that Rg3 promoted Abeta uptake,
      internalization, and digestion. Increased maximal Abeta uptake was observed at 4
      and 8 h after Rg3 pre-treatment (25 microg/mL), and the internalized Abeta was
      almost completely digested from cells within 36 h when pretreated with Rg3
      comparing with single non-Rg3-treated groups. The expression of MSRA (type A MSR)
      was also up-regulated by Rg3 treatment in a dose- and time-dependent manner which
      was coincidently identified in western blots for MSRA proteins in cytosol. These
      results indicate that microglial phagocytosis of Abeta may be enhanced by Rg3 and
      the effect of Rg3 on promoting clearance of Abeta may be related to the MSRA
      associated action of Rg3. Thus, stimulation of the MSRA might contribute to the
      therapeutic potentials of Rg3 in microglial phagocytosis and digestion in the
      treatment of AD.

PMID- 16276975
TI  - Suppressive effects of furonaphthoquinone NFD-37 on the production of
      lipopolysaccharide-inducible inflammatory mediators in macrophages RAW 264.7.
AB  - 2-Methyl-2-(2-methylpropenyl)-2,3-dihydronaphthoquinone[2,3-b]furan-4,9-dione
      (NFD-37) is a synthetic furonaphthoquinone compound. In this study, we determined
      that NFD-37 could inhibit the lipopolysaccharide (LPS)-induced production of
      inflammatory mediators in macrophages RAW 264.7. This compound inhibited LPS
      induced nitric oxide (NO) or prostaglandin (PG) E2 production in dose-dependent
      manners, with IC50 values of 7.2 microM and 5.3 microM, respectively. As the
      positive controls, pyrrolidine dithiocarbamate (30 microM) exhibited a 57%
      inhibition of NO production, and NS-398 (1 microM) manifested a 48% inhibition of
      PGE2 production. The inhibitory effects of NFD-37 on NO and PGE2 production were
      determined to occur in conjunction with the suppression of inducible NO synthase
      or cyclooxygenase-2 expression. NFD-37 also inhibited the production of LPS
      inducible tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6, at IC50
      values of 4.8-8.9 microM. We also determined the anti-inflammatory efficacy of
      NFD-37 using carrageenin-induced paw edema in experimental mice.

PMID- 16276976
TI  - Hepatotoxic effect of 1-bromopropane and its conjugation with glutathione in male
      ICR mice.
AB  - The hepatotoxic effects of 1-bromopropane (1-BP) and its conjugation with
      glutathione were investigated in male ICR mice. A single dose (1000 mg/kg, po) of
      1-BP in corn oil to mice significantly increased serum activities of alanine
      aminotransferase and aspartate aminotransferase. Glutathione (GSH) content was
      dose-dependently reduced in liver homogenates 12 h after 1-BP treatment. In
      addition, 1-BP treatment dose-dependently increased levels of S-propyl GSH
      conjugate at 12 h after treatment, as measured by liquid chromatography
      electrospray ionization tandem mass spectrometry. The GSH conjugate was maximally
      increased in liver at 6 h after 1-BP treatment (1000 mg/kg), with a parallel
      depletion of hepatic GSH content. Finally, 1-BP induced the production of
      malondialdehyde in liver. The present results suggest that 1-BP might cause
      hepatotoxicity, including lipid peroxidation via the depletion of GSH, due to the
      formation of GSH conjugates in male ICR mice.

PMID- 16276977
TI  - Role of NADPH oxidase-mediated generation of reactive oxygen species in the
      mechanism of apoptosis induced by phenolic acids in HepG2 human hepatoma cells.
AB  - Although plant-derived phenolic acids have been reported to have anti-cancer
      activity, the exact mechanism is not completely understood. In this study, we
      investigated the role for reactive oxygen species (ROS) as a mediator of the
      apoptosis induced by caffeic acid (CA) and ferulic acid (FA), common phenolic
      acids in plants, in HepG2 human hepatoma cells. CA and FA reduced cell viability,
      and induced apoptotic cell death in a dose-dependent manner. In addition, they
      evoked a dose-related elevation of intracellular ROS. Treatment with various
      inhibitors of NADPH oxidase (diphenylene iodonium, apocynin, neopterine)
      significantly blunted both the generation of ROS and the induction of apoptosis
      induced by CA and FA. These results suggest that ROS generated through activation
      of NADPH oxidase may play an essential role in the apoptosis induced by CA and FA
      in HepG2 cells. These results further suggest that CA and FA may be valuable for
      the therapeutic management of human hepatomas.

PMID- 16276978
TI  - Determination of mequitazine in human plasma by gas-chromatography/mass
      spectrometry with ion-trap detector and its pharmacokinetics after oral
      administration to volunteers.
AB  - The objective of this study was to develop an assay for mequitazine (MQZ) for the
      study of the bioavailability of the drug in human subjects. Using one mL of human
      plasma, the pH of the sample was adjusted and MQZ in the aqueous phase extracted
      with hexane; the organic layer was then evaporated to dryness, reconstituted and
      an aliquot introduced to a gas chromatograph/mass spectrometer (GC/MS) system
      with ion-trap detector. Inter- and intra-day precision of the assay were less
      than 15.1 and 17.7%, respectively; Inter- and intra-day accuracy were less than
      8.91 and 18.6 %, respectively. The limit of quantification for the current assay
      was set at 1 ng/mL. To determine whether the current assay is applicable in a
      pharmacokinetic study for MQZ in human, oral formulation containing 10 mg MQZ was
      administered to healthy male subjects and blood samples collected. The current
      assay was able to quantify MQZ levels in most of the samples. The maximum
      concentration (Cmax) was 8.5 ng/mL, which was obtained at 10.1 h, with mean half
      life of approximately 45.5 h. Under the current sampling protocol, the ratio of
      AUCt-->last to AUCt-->infinity was 93.4%, indicating that the blood collection
      time of 216 h is reasonable for MQZ. Therefore, these observations indicate that
      an assay for MQZ in human plasma is developed by using GC/MS with ion-trap
      detector and validated for the study of pharmacokinetics of single oral dose of
      10 mg MQZ, and that the current study design for the bioavailability study is
      adequate for the drug.

PMID- 16276979
TI  - Effect of Cimetidine and Phenobarbital on metabolite kinetics of Omeprazole in
      rats.
AB  - Omeprazole (OMP) is a proton pump inhibitor used as an oral treatment for acid
      related gastrointestinal disorders. In the liver, it is primarily metabolized by
      cytochrome P-450 (CYP450) isoenzymes such as CYP2C19 and CYP3A4. 5
      Hyroxyomeprazole (5-OHOMP) and omeprazole sulfone (OMP-SFN) are the two major
      metabolites of OMP in human. Cimetidine (CMT) inhibits the breakdown of drugs
      metabolized by CYP450 and reduces the clearance of coadministered drug resulted
      from both the CMT binding to CYP450 and the decreased hepatic blood flow due to
      CMT. Phenobarbital (PB) induces drug metabolism in laboratory animals and human.
      PB induction mainly involves mammalian CYP forms in gene families 2B and 3A. PB
      has been widely used as a prototype inducer for biochemical investigations of
      drug metabolism and the enzymes catalyzing this metabolism, as well as for
      genetic, pharmacological, and toxicological investigations. In order to
      investigate the influence of CMT and PB on the metabolite kinetics of OMP, we
      intravenously administered OMP (30 mg/kg) to rats intraperitoneally pretreated
      with normal saline (5 mL/kg), CMT (100 mg/kg) or PB (75 mg/kg) once a day for
      four days, and compared the pharmacokinetic parameters of OMP. The systemic
      clearance (CLt) of OMP was significantly (p<0.05) decreased in CMT-pretreated
      rats and significantly (p<0.05) increased in PB-pretreated rats. These results
      indicate that CMT inhibits the OMP metabolism due to both decreased hepatic blood
      flow and inhibited enzyme activity of CYP2C19 and 3A4 and that PB increases the
      OMP metabolism due to stimulation of the liver blood flow and/or bile flow, due
      not to induction of the enzyme activity of CYP3A4.

PMID- 16276980
TI  - [Problems of drinking water supply in Russia in the system of international
      actions on "Water and health. Optimization of solution ways"].

PMID- 16276981
TI  - [Disinfectology as a forerunner of future denoxology].
AB  - Under available pollution of the environment particularly with persistent
      physical, chemical, and biological pathogens, it is insufficient not only to
      protect it, but it is necessary to implement measures for their active
      decontamination (denoxation) just in the environment. Environmental
      decontamination of biological (infective) pathogens has been both
      methodologically and technologically developed to the present day. The
      theoretical and methodical bases of disinfectology as a functioning section of a
      non-existing (up to now?), but necessary area of hygienic science--denoxology.

PMID- 16276982
TI  - [Hygienic aspects of human sensitization under the influence of biological
      factors of the dwelling environment].
AB  - The paper deals with the risk of occurrence and development of allergic diseases
      under the influence of biological housing factors, such as molds, staphylococci,
      ticks, and insects. It shows that biological domestic allergens are of high
      importance in human sensitization. There is evidence that supports the allergic
      hazard of the above factors to children and adults.

PMID- 16276983
TI  - [Risk factors and incidence of dental diseases in children in a large industrial
      town].
AB  - A relationship has been studied between somatic diseases, functional changes, and
      dental mortality in children living in urban areas having different levels of
      ambient air pollution. Visceral diseases have been ascertained to contribute to
      the development or deteriorate the course of various pathological tooth and jaw
      processes. Systemic diseases change the conditions of formation and maturation of
      dentins, which makes them less resistant. The relationship between the changes in
      the somatic and dental statuses of children is more pronounced when the
      ecological situation is poor.

PMID- 16276984
TI  - [Impact of stress on hepatic lipid and carbohydrate metabolism, prevention].
AB  - An oligomer proantocyanidine complex (OPCC) isolated from the aqueous-and
      alcoholic extract Kalifen and a polyphenol complex (PPC) isolated from the
      eleutherococcus extract were tested for their effects on carbohydrate and lipid
      metabolism in the rat liver under acute stress caused by hanging up of the
      animals by the cervical fold for 22 hours. This acute stress was accompanied by
      decreases in aerobic glycolysis and pentose cycle and by an increase in
      lipolysis. Hepatic etherifying function impaired. Lipids became predominant
      energy substrates. The administration of OPCC and PPC during stress promoted the
      preservation of carbohydrate metabolic reactions (gluconeogenesis,
      pentosephosphate pathway, Krebs cycle) and to the decrease of lipolysis. OPCC was
      shown to have stress-protective properties and to be able to diminish adrenal
      hypertrophy, to increase the production of oxidized equivalents (NAD+), and to
      enhance the activity of G-6-PDH in the rat liver. The complex is superior to the
      well-known antistress agent eleutherococcus, which makes it possible to regard
      these drugs as possible promising drugs in preventive and rehabilitative
      medicine.

PMID- 16276986
TI  - [Hygienic assessment of the influence of climatic factors on the prevalence of
      respiratory diseases in the Primorye Territory].
AB  - A methodology is proposed to assess environmental factors on human health, which
      is a new type of analyses and helps to substantiate managerial solutions in human
      health promotion and environmental protection. Stages and an algorithm of
      calculation of the risk of prevalence of diseases are presented, which has
      established cause-effect relationships between the climatic parameters and the
      incidence of respiratory diseases in different age groups and different
      bioclimatic zones. The established threshold criteria permit a rapid estimation
      of the influence of environmental factors on morbidity rates and provides a
      system conception for the development of a complex of therapeutic-and
      prophylactic measures.

PMID- 16276985
TI  - [Disacarification in the prevention of allergic diseases].
AB  - Elimination of domestic dust mites (Acariformes: Pyroglyphidae) from the premises
      is a significant factor of improving the quality of life in individuals with mite
      borne sensitization. Some ways of reducing the number of domestic dust mites in
      the premises are considered.

PMID- 16276987
TI  - [Ambient air pollution and its impact on the incidence of respiratory diseases in
      children].
AB  - The increased number of ecological problems in Russia has stimulated the
      development of methodological approaches to studying a human chemical load under
      the conditions of an industrial town. The data on mortality in children under 3
      years of age, who lived in a developed industrial town, have been analyzed.
      Comparison of data on ambient air purity and those on the incidence of
      respiratory disease has established a correlation between environment pollution
      and the likelihood of diseases in children under the influence of harmful
      factors.

PMID- 16276988
TI  - [Estimation of doses of irradiation with radon-222 and its degradation products
      in adults of Tomsk].
AB  - The paper presents the results of statistical processing of experimental data on
      the volumetric activity of radon within the premises of various buildings. The
      results were used to estimate internal radiation doses of inhaled radon and its
      short-lived degradation products in the population of Tomsk. The average annual
      population-weighed value of the effective dose was 1.24 mSv, which is 1.5-times
      higher than the estimated value for the Russian Federation.

PMID- 16276989
TI  - [Hygienic evaluation of genotoxic effects during artificial air ionization].
AB  - The study examined the potential genotoxic activity and the impact of artificial
      air ionization on lifespan. Experiments on Drosophila melanogaster demonstrated
      that exposure of the lung to negative (5 x 10(4), 5 x 10(5), and 10(6) ion/cm3)
      and slight positive (5 x 10(4), 5 x 10(5), and 10(6) ion/cm3) airoions generated
      on the electrodes at direct-current voltage failed to increase the frequency of
      dominant lethal mutations in the gametes and to affect the life-span of male
      flies. Exposure of the flies to deionized air increased the rate of early
      embryonic lethal mutations.

PMID- 16276990
TI  - [Species diversity of staphylococci in the air and the organism of carriers upon
      technogenic chemical exposure].
AB  - The authors analyzed the biological diversity of sanitary indicative
      microorganisms of the genus Staphylococcus in man and environmental objects in an
      area adjacent to a gas industrial enterprise. The species diversity of
      staphylococci was found to increase upon technogenic chemical exposure, which was
      recorded in both ambient air and bacterial carriers. The rise in the biological
      diversity was shown to occur with the increased number of rare species which
      adequate assessment required the use of the Shennon index. Whether the index of
      biological species diversity of staphylococci during microbiological monitoring
      of natural ecological systems is discussed in the paper.

PMID- 16276991
TI  - [Energy requirements in young males under extreme activity conditions].
AB  - Energy expenditures were studied in young men when the latter performed their
      professional activities under extreme living conditions (strenuous exercises, a
      combined exposure to natural factors: high environmental temperature, longer
      exposure to solar ultraviolet radiation, complex piedmont relief, etc:). The
      average daily energy expenditure calculated by metabolic constants was 4570 kcal
      or 19070 kJ and the recommended calorie content of a diet is 5250 kcal.

PMID- 16276992
TI  - [Assessment of occupational risk at glass-making enterprises].

PMID- 16276993
TI  - [Preventive antifluorotic effect of breastfeeding].

PMID- 16276994
TI  - [Hemodynamic parameters in schoolchildren under examination stress].
AB  - During examinations, cardiovascular and mental changes were studied in
      schoolchildren studying in middle (5-7) forms with a differentiated form of
      teaching. Cardiac hemodynamic values were calculated and a psychological testing
      for anxiety was performed in the examinees. During an examination session, the
      schoolchildren were ascertained to develop emotional stress characterized by a
      complex of psychophysiological and autonomic nervous changes.

PMID- 16276995
TI  - [Health status and academic progress in students of a physical education
      institute].
AB  - A factorial correlation was found between the indices of the social health of the
      student collective of a physical education institute (total mortality) and those
      of academic progress on one hand and the factors characterizing the sportive
      training stress, living conditions, health status, and life-style of the
      students, on the other.

PMID- 16276996
TI  - [Ways of enhancing mentality in schoolchildren from an iodine-deficiency region].
AB  - Mentality was studied in 537 schoolchildren aged 7-8, 10-11, and 15-16 years who
      lived in an iodine-deficiency region. Its low level was found in 71% of the
      children. A comprehensive program was worked out and used to enhance the
      schoolchildren's mentality in iodine deficiency. It included the use of
      Iodomarine in a dose of 100 microg/day, lectures for and discussions with the
      children and their parents, dissemination of information materials on iodine
      deficiency and sequels. The program was implemented in the study group during an
      academic year. After prophylaxis, the sizes of the thyroid became normal in 21%
      of the children in the study group. There was a reduction in the number of
      patients with decreased attention, memory, and thinking from 49.8 to 20.7%, from
      38.7 to 22.5%, and from 23.2 to 15.1%, respectively. Anxiety grade decreased in
      14.7% of the pupils. A more beneficial effect was observed in junior-form pupils.
      The obtained results made it possible to define the informative indices of
      decreased mentality in schoolchildren due to iodine deficiency.

PMID- 16276997
TI  - [The functional status of students carrying a mental load].
AB  - The paper shows psychological and cardiac hemodynamic changes in students
      performing an hour mental test of a program on a computer. There are synchronous
      reductions in the magnitude of cardiac hemodynamic indices and in the activity of
      the sympathetic pattern of cardiac rhythm regulation in the examinees.

PMID- 16276998
TI  - [Hygienic characteristics of children's sports-and-playing grounds in Moscow].
AB  - The hygienic state of 280 children's sports-and-playing grounds was studied in 9
      Moscow okrugs in accordance with the proportion of vandalism and the level of
      greening, noise, and environmental pollution caused by motor transport.
      Technogenic load on children on the children's grounds was shown to be higher in
      Moscow than that in its Region, the levels of dust, chlorine ions, lead, and
      potassium were 10, 3, 5, and 2 times higher in Moscow than in the region. By
      significantly decreasing the pollution, the minimum distance of children's
      grounds from a road or a car park should be 15 m. It was found that 33-50% of the
      children's grounds in Moscow did not meet this criterion. The level noise more
      than 40 dB caused by motor transport on the children's grounds was noted in 53%
      of cases. The level of poor greening was directly correlated with that of noise.
      The problem associated with the durability of constructions for children's
      grounds (the broken constructions were an average of about 12.5%) may be solved,
      by using fiberglass materials.

PMID- 16276999
TI  - [Characterization of the physical development of schoolchildren in different
      regions of Russia].
AB  - Age-related changes in some physical development (PD) indices (height, weight,
      chest circumference, hand dynamometry, and vital capacity) were studied in 21,500
      schoolchildren aged 7 to 17 years in 5 federal areas (Central, North-western,
      Urals, Southern, and Siberian) of the Russian Federation. The moderate
      development of both morphological and functional characteristics is prevalent in
      the school-children of all age groups, the proportion of their low development
      being higher than that of their high development. The proportion of children with
      average weight is virtually constant in age groups of 7 to 17 years and it is
      about 50% of the sample. The moderate level of other characteristics is noted for
      age-related variations of different intensity, which are more pronounced in
      girls. In terms of age, the functional parameters of PD are more variable than
      morphological ones. Age-related variation of the ratio of PD levels may be
      entirely assigned due to: a) heterochronicity of processes of increasing
      morphological parameters (longitudinal and latitudinal); b) a great variability
      of functional parameters. Recommendations on correction of schoolchildren's PD
      with physical educational means are given.

PMID- 16277000
TI  - [Correction of iron and immune deficiencies in students from a higher
      humanitarian educational establishment].
AB  - Examinations of 29 female students of a study medical group have ascertained that
      daily addition of vitamins (ascorutin, thiamin, riboflavin, pyridoxine,
      cyanocobalamin, and folic acid) to a diet resulted in a slight enhancement in
      trace element metabolism and hence in an increase in the intestinal and renal
      excretion of iron, copper, and manganese. Two-week dietary supplement of vitamins
      in combination with trace elements (iron, copper, and manganese) caused a
      considerable retention of iron and manganese concurrently with a higher excretion
      of copper from the body. At the same time, the higher rate of hemopoiesis and the
      elevated plasma levels of iron and formed blood elements, and the rise in non
      specific responsiveness and physical fitness were more noticeable as compared to
      their normal values. A significant positive correlation was found between the
      direct and indirect indices of iron metabolism on one hand and the parameters of
      natural immunity defense and physical fitness on the other.

PMID- 16277001
TI  - [Analysis of human health in the sociohygienic monitoring system at a regional
      level].

PMID- 16277002
TI  - [Results of sociohygienic monitoring in Kazan].

PMID- 16277003
TI  - [Dust responsible for reproduction dysfunction].

PMID- 16277004
TI  - [A combined effect of toluene and general vibration in a chronic toxicological
      experiment].

PMID- 16277005
TI  - [Impact of an industrial-frequency magnetic field and fixed light on rat
      peripheral blood].

PMID- 16277006
TI  - Biological effects of a software-controlled voltage pulse generator (PhyBack PBK
      2C) on the release of vascular endothelial growth factor (VEGF).
AB  - BACKGROUND: Electrical stimulation (ES) may induce vascular permeability and
      physiological angiogenesis. ES of rat muscles significantly increases the
      microvessel density and vascular endothelial growth factor (VEGF) protein levels.
      Thus, a pilot study was designed to analyze the effects of low-voltage electric
      impulses on VEGF levels in patients with dystrophic ulcers. MATERIALS AND
      METHODS: Circulating VEGF levels were analyzed in 9 patients undergoing an ES
      session with low voltage software-controlled impulses applied through topical
      transducers (1-9 micros width, 1-420-Hz frequency and 30-120 V strength-100
      microA max). RESULTS: The session was accompanied by a peak of circulating VEGF
      (3-10 min from start) in all 9 patients, which was preceded by a rise of TNF
      alpha (2-min) and was independently associated with soluble E-selectin levels.
      Nitric oxide generation was significantly improved on the day after treatment. No
      hemostatic activation or sustained inflammatory reaction were observed.
      CONCLUSION: ES may represent a safe method for augmenting VEGF-mediated vascular
      protection, either directly or by induction of NO.

PMID- 16277007
TI  - Comparison of transforming growth factor-beta/Smad signaling between normal
      dermal fibroblasts and fibroblasts derived from central and peripheral areas of
      keloid lesions.
AB  - BACKGROUND: Keloids are benign proliferations of fibroblasts, but their exact
      etiology and molecular pathogenesis are unknown. MATERIALS AND METHODS:
      Fibroblasts were isolated from the central and peripheral regions of keloids, and
      the growth behavior and molecular characteristics of the keloid fibroblasts were
      compared with those of age-adjusted normal dermal fibroblasts. RESULTS: Central
      (but not peripheral) keloid fibroblasts exhibited significantly increased growth
      and high levels of expression of transforming growth factor-beta (TGF-beta)
      receptor 1 and Smad 2/3. CONCLUSION: Proliferation of central keloid fibroblasts,
      which results in keloid formation, appears to mainly involve the TGF-beta/Smad
      pathway.

PMID- 16277008
TI  - Protection of esophageal multi-lineage progenitors of squamous epithelium (stem
      cells) from ionizing irradiation by manganese superoxide dismutase
      plasmid/liposome (MnSOD-PL) gene therapy.
AB  - BACKGROUND: Intraesophageal manganese superoxide dismutase plasmid liposome
      (MnSOD-PL) gene therapy protects against irradiation damage. MATERIALS AND
      METHODS: To determine whether esophageal side population (SP) stem cells were
      protected, epitope-tagged (hemagglutinin) (HA) MnSOD-PL was administered to
      C57BL/6J mice 24 hours prior to 30 Gy esophageal irradiation. SP cells were
      isolated, and apoptosis and multi-lineage vimentin/endothelin/F4/80 (macrophage)
      colonies in vitro were quantitated. RESULTS: The number and percent of SP cells,
      apoptotic cells, or numbers of multi-lineage vimentin/endothelin/F4/80-positive
      in vitro colonies isolated from non-irradiated HA-MnSOD-PL-treated or 30 Gy
      irradiated esophagus did not differ between groups. Irradiation in vitro
      significantly increased apoptosis in explanted non-SP cells from control (p =
      0.021) compared to MnSOD-PL-treated mice. Irradiation-induced cell division was
      significantly increased in SP cells from control-irradiated mice (p = 0.001), but
      not MnSOD-PL-treated mice. Irradiation-induced apoptosis detected in vivo at 5
      days was decreased by MnSOD-PL. CONCLUSION: MnSOD-PL gene therapy protects
      esophageal SP cells from irradiation in vitro and in vivo.

PMID- 16277009
TI  - Gastric duplication cyst in an adult: case report.
AB  - Duplication cysts of the stomach are uncommon findings in adult patients and
      diagnosis is often overlooked. Presenting symptoms are often non-specific, but
      complications, including chronic infections, ruptures or carcinoma arising in the
      cyst, are rare. We report a case of a non-communicating cyst of the stomach in a
      67-year-old man.

PMID- 16277010
TI  - Hidden chromosome 8 abnormalities detected by FISH in adult primary
      myelodysplastic syndromes.
AB  - Acquired clonal chromosomal abnormalities are found in about 30-50% of primary
      myelodysplastic syndromes (MDS). These abnormalities are predominantly
      characterized by total/partial chromosomal losses or gains and rarely by balanced
      structural aberrations. Trisomy 8 represents the most common chromosomal gain. In
      the present study, the numerical aberration of chromosome 8 was evaluated by the
      fluorescence in situ hybridization (FISH) technique in MDS, and the results
      compared with those of conventional cytogenetics. Thirty adult patients with
      primary MDS, 17 with a normal karyotype and 13 with several chromosomal
      abnormalities except chromosome 8, were included in this study. On comparing the
      results of FISH and conventional cytogenetics, a superiority of FISH over the
      karyotype was detected in 3 cases. In one of them, further cytogenetic analysis
      confirmed the FISH results. Nevertheless, the FISH technique has limitations,
      detecting only abnormalities specific for the target FISH probe used In clinical
      practice, conventional cytogenetics continues to be the basic technique for MDS
      patient evaluation. However, a large number of metaphases, even those of poor
      quality, must be analyzed in each case. The FISH technique could be considered to
      be complementary to achieve a more accurate analysis.

PMID- 16277011
TI  - Diagnostic accuracy of MRI for preoperative staging of pancreatic carcinoma:
      tendency for understaging.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of magnetic resonance imaging
      (MRI) for preoperative staging in pancreatic carcinoma. MATERIALS AND METHODS:
      MRI investigations, including MR-angio and MR-cholangiopancreatography (MRCP) of
      19 patients who underwent surgery for pancreatic carcinoma were retrospectively
      evaluated by two radiologists. The size, localization of the tumor and possible
      infiltration of neighboring organs, as well as the presence of enlarged lymph
      nodes, were determined to define a preoperative, radiological TN stage. Lymph
      node metastasis was defined as peripancreatic lymphoma greater than 10 mm. Our
      findings were correlated to postoperative diagnosis. RESULTS: The T-stage was
      correctly evaluated in 52.6% of the cases (10/19). Understaging took place in
      31.6% (6/19) and overstaging in 15.8% (3/19). In three cases of understaging, a
      micro-infiltration of the peripancreatic tissue was not visible in MRI.
      Pathologically enlarged lymph nodes were correctly found in 63.2% of the cases
      (12/19). Overstaging took place in 21.1% of the cases (4/19) and understaging in
      15.8% (3/19). CONCLUSION: MRl for preoperative staging of pancreatic carcinoma
      showed a tendency to understage tumor size in this study population. Especially
      in cases of small tumor size, micro-infiltration of peripancreatic tissue or the
      common bile duct may not be detected by MRI. Concerning N-stage, the 95%
      confidence interval reveals a distribution of over- and understaged.

PMID- 16277012
TI  - Effects of probiotic bacteria (VSL#3) on the polyamine biosynthesis and cell
      proliferation of normal colonic mucosa of rats.
AB  - BACKGROUND: Probiotics seem to possess tumour inhibitory properties, but few
      studies have investigated their actions on the cell proliferation of normal
      colonic mucosa. The effects of a probiotic mixture (VSL#3) on polyamine
      biosynthesis, Ki-67 levels and apoptosis in the normal colon of rats were
      studied. MATERIALS AND METHODS: For a 4-week period, 20 rats were fed a VSL#3
      solution and 20 rats a saline solution. Samples from the colonic mucosa were
      collected at the end of treatment. Polyamines were detected by HPLC, ornithine
      decarboxylase activity by a radiometric technique, and apoptosis and Ki-67 by
      histochemical and immunohistochemical methods. RESULTS: VSL#3 caused a
      significant decrease in colonic polyamine levels, ornithine decarboxylase
      activity and Ki-67 compared to controls. A significant increase in the apoptotic
      index was also observed. CONCLUSION: Probiotics could also reduce proliferation
      rates in a condition not affected by hyperproliferative or neoplastic growth,
      when the normal control mechanisms are still completely effective.

PMID- 16277013
TI  - MnSOD-plasmid liposome gene therapy decreases ionizing irradiation-induced lipid
      peroxidation of the esophagus.
AB  - BACKGROUND: Ionizing irradiation-induced cellular and tissue damage is mediated
      in part by resultant radiochemical reactions and resultant oxidative stress.
      Irradiation-induced reactive oxygen and nitrogen species include: superoxide,
      nitric oxide, hydroxyl radical and hydrogen peroxide. The biochemical combination
      of superoxide and nitric oxide radicals forms peroxynitrite, a potent oxidant
      known to induce lipid peroxidation. MATERIALS AND METHODS: The antioxidant
      capacity and lipid peroxidation of the esophagus were determined following
      irradiation. RESULTS: In the present studies, measurements of total antioxidant
      capacity did not change in the esophagus of control irradiated or control plasmid
      pNGVL3-PL intraesophageally-injected mice. In contrast, manganese superoxide
      dismutase-plasmid/liposome (MnSOD-PL) intraesophageally-treated mice showed a
      significant increase in antioxidant capacity persisting for seven days. Lipid
      peroxidative changes induced in the control irradiated mouse esophagus decreased
      over seven days after irradiation of C3H/HeNHsd mice exposed to 37 Gy in a single
      fraction. MnSOD-PL radioprotective gene therapy administered intraorally 24 hours
      prior to irradiation did not significantly reduce the kinetics of induction of
      total peroxidated lipids over the first seven days after irradiation but did
      decrease lipid peroxidation at days 14 and 21. CONCLUSION: These studies
      demonstrate the antioxidant function of MnSOD-PL gene therapy to the esophagus,
      which is detectable as a reduction in irradiation-induced lipid peroxidation.

PMID- 16277014
TI  - Kinetic study of the radical-scavenging activity of vitamin E and ubiquinone.
AB  - Quantitative in vitro studies of antioxidant activities have been performed under
      aerobic conditions. However, since the biological system has lower oxygen
      tension, the effectiveness of antioxidants may be considerably different in vivo.
      alpha-Tocopherol, in vivo the most active tocopherol, is a very poor antioxidant
      in vitro. To clarify these points, the radical-scavenging activities of vitamin E
      (Toc) (alpha-, beta-, gamma- and delta-tocopherols) and ubiquinone were evaluated
      by the induction period method from the kinetics of polymerization of methyl
      methacrylate (MMA) initiated by thermal decomposition of
      2,2'azobisisobutyronitrile (AIBN) (alkyl radical, R*), or benzoyl peroxide (BPO)
      (peroxyl radical, PhCOO*) under nearly anaerobic conditions. The ratio of the
      rate constant of inhibition to that of propagation (k(inh)/k(p)) for Toc was
      about 10 in a system with a molar ratio of AIBN to Toc of 100:1, whereas in the
      corresponding BPO system k(inh)/k(p) declined in the order alpha (47) > beta (15)
      > gamma (10) > delta (7). In contrast, with AIBN the number of free radicals
      trapped by the phenolic moiety (n) declined in the order delta (3.0) > gamma
      (2.5) > alpha (2.2) > beta (1.6), whereas with BPO n declined in the order delta
      (1.9) > gamma (1.4) > beta (1.0) > alpha (0.3). A similar tendency was found in
      systems with a molar ratio of 10:1. Also, ubiquinone-10 showed radical-scavenging
      activity, although the n (0.02) was much less than that for Toc. The low n value
      for alpha-Toc (n = 0.3) may be attributed to the formation of stable alpha-Toc
      during the induction period. With a n = about 1 for beta- and gamma-Toc, a
      dimerization coupling of Tocs is suggested. Thus, the radical-scavenging activity
      is affected by the number and position of the methyl groups in the benzene
      nucleus of the various tocopherol compounds.

PMID- 16277015
TI  - Impairments of the 2-5A synthetase/RNase L pathway in chronic fatigue syndrome.
AB  - This paper provides an overview of the evidence addressing the impairments of the
      2'-5' oligoadenylate (2-5 A) synthetase/RNase L pathway in Chronic Fatigue
      Syndrome (CFS) patients. The 2-5A synthetase/RNase L pathway in CFS patients
      appears to be both up-regulated (i.e. increased levels of bioactive 2-5A
      synthetase and increased activity of the RNase L enzyme) and deregulated
      (elastase and calpain initiate 83 kDa RNase L proteolysis, generating two major
      fragments with molecular masses of 37 and 30 kDa, respectively). The deregulation
      of the 2-5A synthetase/RNase L pathway in CFS accompanies decreased NK-function
      and deregulation of apoptotic pathways. Since various components of the pathway
      appear to be related to performance during a graded exercise stress test, some
      evidence supportive of the clinical importance of the impaired pathway in CFS
      patients has been provided. Studies addressing the treatment of the deregulation
      of the 2-5A synthetase/RNase L pathway in CFS are warranted.

PMID- 16277016
TI  - Bipolar radiofrequency induced thermotherapeutic volumetric reduction of VX2
      metastases in an animal model.
AB  - BACKGROUND: Radiofrequency-induced thermotherapy has shown promising results in
      the palliative treatment of various tumor entities. The purpose of this study was
      to investigate the effectiveness of bipolar radiofrequency volumetric tissue
      reduction (VTR) on lymph node (LN) metastases in the VX2 SCC model. MATERIALS AND
      METHODS: Six male New Zealand white rabbits, with palpable metastatic disease
      within the parotid lymph nodes, were treated using the Celon-ProSurge probe,
      needle length 10 mm, diameter of 2.3 mm. The animals were sacrificed on the 4th,
      8th, 11th, 14th, 18th and 22nd postoperative days respectively. RESULTS AND
      CONCLUSION: Bipolar radiofrequency VTR could prevent progression of local
      metastatic disease in one-third of the animals compared to the control group of
      untreated VX2 carcinoma rabbits. These results encourage further studies,
      directed at whether this treatment modality could play a role in the palliative
      therapy of metastatic LN. Future studies should concentrate on the refinement of
      the treatment parameters and optimization of the treatment duration.

PMID- 16277017
TI  - Effects of colestimide and/or Bofu-tsusho-san on plasma and liver lipids in mice
      fed a high-fat diet.
AB  - Hypercholesterolemia is known to enhance the risk of coronary heart disease and
      fatty liver. Colestimide is an anion-exchange resin, which is not absorbed in the
      small intestine, decreases the intestinal reabsorption of bile acids synthesized
      from cholesterol in the liver and consequently increases bile acid excretion into
      the feces. Bofu-tsusho-san, a traditional Japanese herbal remedy, contains 18
      components and has long been used as an anti-obesity agent. In the present study,
      we investigated the effects of colestimide and/or Bohu-tsusho-san in young male
      mice fed a high-fat diet. The high-fat diet supplemented with both colestimide
      and Bofu-tsusho-san markedly reduced the plasma levels of lipids, the liver
      weight and number of fatty droplets in the liver cytoplasm, and the body growth,
      compared with animals fed a high-fat diet alone. Neither medicine affected the
      blood biochemistry. Thus, the hypocholesterolemic action of colestimide,
      sometimes bringing light flatulence, which is improved by simultaneous
      administration of Bofu-tsusho-san, which activates the thermogenesis of brown
      adipose tissue, is suggested to reduce body mass and liver lipids, lowering the
      plasma levels of lipids.

PMID- 16277018
TI  - Increased plasma levels of zinc in obese adult females on a weight-loss program
      based on a hypocaloric balanced diet.
AB  - Zinc is required for many biological functions including DNA synthesis, cell
      division, gene expression and the activity of various enzymes in humans and
      animals. Zinc concentrations in the plasma and erythrocytes are lower and urinary
      zinc excretion and serum insulin levels are higher in subjects with obesity. The
      effects of a weight-loss program based on a hypocaloric balanced diet were
      investigated on 23 obese females, who had a body mass index of more than 25.0 and
      had dieted for 6 months at the Nutrition Clinic, Institute of Nutrition Sciences,
      Kagawa Nutrition University, Tokyo, Japan. The subjects ranged in age from 29 to
      76 (54.3 +/- 13.0) years old. The hypocaloric balanced diet significantly reduced
      the body weight, body mass index, body fat percentage and amount of body fat with
      a slight lowering of blood pressure and plasma levels of triglyceride.
      Interestingly, the plasma concentrations of zinc were markedly enhanced at the
      end of the program.

PMID- 16277019
TI  - Theoretical prediction of the relationship between phenol function and COX-2/AP-1
      inhibition for ferulic acid-related compounds.
AB  - Ferulic acid-related compounds possess antioxidant activity. Dehydrodiisoeugenol
      and ferulic acid dimer (bis-FA), but not the parent monomers isoeugenol and
      ferulic acid, inhibit lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2)
      gene expression in RAW 264.7 cells. To clarify the mechanism of their inhibitory
      effects on COX-2 expression, the phenolic O-H bond dissociation enthalpy (BDE)
      and ionization potential (IP) of 8 ferulic acid-related compounds were calculated
      by both semi-empirical molecular orbital (AM1, PM3) and ab initio (3-21G* 6-31G*)
      and density function theory (DFT) (B3LYP) methods. COX-2 inhibition appeared in
      compounds with phenolic O-H BDE higher than 85.76 kcal/mol, as calculated by the
      density function theory (DFT) approach. The phenolic O-H BDEs of the most potent
      compounds, dehydrodiisoeugenol and bis-FA, were 85.99 and 85.76 kcal/mol,
      respectively. No causal relationship between COX-2 inhibition and IP was found.
      Neither dehydrodiisoeugenol nor bis-FA possessed significant scavenging activity
      against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. The NSAID-like activity
      of dehydrodiisoeugenol and bis-FA appears to be related to their phenol function.
      Binding of activator protein-1 (AP-1) to the 12-tetradecanoylphorbol-13-acetate
      responsive element (TRE) sequence in LPS-stimulated cells was inhibited by bis-FA
      at 1 microM and dehydrodiisoeugenol at 0.1 microM, but not by the parent monomers
      isoeugenol and ferulic acid.

PMID- 16277020
TI  - Targeting the tumor vasculature: enhancing antitumor efficacy through combination
      treatment with ZD6126 and ZD6474.
AB  - BACKGROUND: The antitumor efficacy of combination therapy of the vascular
      disrupting agent ZD6126 and antiangiogenic agent ZD6474 was evaluated in the
      models of human colorectal (HT29) and ovarian carcinoma (OW1). MATERIALS AND
      METHODS: HT29 and OW1 xenograft-bearing mice were treated with ZD6126 and ZD6474
      either alone or in combination. ZD6126 therapy consisted of three doses of 100
      mg/kg administered 1, 3 and 5 days after the tumor reached the starting size.
      ZD6474 was administered daily at a dose of 25 mg/kg on days 1-5. RESULTS: ZD6126
      and ZD6474 treatment alone only resulted in modest tumor growth delay. However,
      significantly enhanced antitumor effects were observed in the combination
      treatment. CONCLUSION: The combination of the vascular disrupting with the
      antiangiogenic agent led to significant enhancement of antitumor efficacy in HT29
      and OW1 human tumor models. Such combination therapy may have significant
      therapeutic benefit even in tumors insensitive to either treatment alone.

PMID- 16277021
TI  - Spontaneous intestinal melanoma in dogs.
AB  - Primary melanoma of the gastrointestinal tract is a rare, highly malignant
      neoplasm that is associated with an unfavorable long-term prognosis. Animal
      studies are needed to further characterize this tumor and to develop new and more
      effective protocols. A spontaneous canine intestinal melanoma is described which,
      because of its local aggressive behavior and advanced stage, was not treatable
      with conventional strategies, thus being a potential candidate for
      investigational trials.

PMID- 16277022
TI  - MRI and bone scan imaging in the preoperative evaluation of painful vertebral
      fractures treated with vertebroplasty and kyphoplasty.
AB  - BACKGROUND: This study compared the role and timing of bone scintigraphy and
      magnetic resonance imaging (MRI) in the evaluation of vertebral compression
      fractures (VCFs), before treatment with vertebroplasty and kyphoplasty. To our
      knowledge, no prior articles have described, in osteoporotic and pathological
      vertebral fractures, the role of MRI and bone scintigraphy as pre-procedural work
      up in those patients candidated to undergo spinal interventional procedures.
      MATERIALS AND METHODS: A retrospective chart review was performed of thirty
      patients treated with interventional procedures for painful vertebral fractures
      at our institution between January 2002 and July 2003. RESULTS: In patients,
      selected after evaluation with MRI and bone scan imaging, both procedures
      demonstrated swift pain relief associated with vertebral resistance augmentation.
      CONCLUSION: MRI revealed itself to be equivalent to bone scan imaging in
      selecting patients to be treated with vertebroplasty and kyphoplasty in the first
      3/4 months, while bone scintigraphy was more accurate in the evaluation of
      elderly fractures (> 3/4 months). MRI was superior to bone scintigraphy in
      vertebral collapses due to multiple myeloma.

PMID- 16277023
TI  - Effects of 5-methoxypsoralen (5-MOP) on arylamine N-acetyltransferase activity in
      the stomach and colon of rats and human stomach and colon tumor cell lines.
AB  - BACKGROUND: It has been shown that cytochrome P450 enzymes (CYPs) and
      acetyltransferase can be used as biomarkers of carcinogen-DNA adduct levels and
      human cancer susceptibility. The gastrointestinal tract is the portal of entry of
      foreign compounds and presents xenobiotic metabolizing N-acetyltransferase (NAT)
      and CYPs activities. 5-Methoxypsoralen (5-MOP) has been used in combination with
      UV radiation in skin photochemotherapy for decades. A number of studies have
      demonstrated that 5-MOP is inhibitory towards mouse and human CYP isoforms, but
      investigations on the direct effects on NAT activity in laboratory animals and
      human cancer cells are limited. The main objective of this study was to document
      the effects of 5-MOP on the modulation of NAT activities in the stomach and colon
      of rats and human stomach and colon tumor cell lines. MATERIALS AND METHODS: N
      Acetylation of 2-aminofluorene (AF) to 2-acetylaminofluorene (AAF) by NAT in the
      stomach and colon of Sprague-Dawley (SD) rats and in human stomach (SC-M1) and
      colon (COLO 205) tumor cell lines was investigated. RESULTS: The data show that
      the metabolic activity of NAT in the rat colon was higher than that in the rat
      stomach, and the further metabolism of AAF was slower in the stomach than in the
      colon. 5-MOP increased the activity of NATand also increased the further
      metabolism of AAF at 24 h in the rat stomach. In the rat colon, no statistically
      significant changes caused by 5-MOP were observed in NAT activity, but 5-MOP
      increased the further metabolism of AAF at 24 to 72 h. 5-MOP decreased the
      activity of NAT only at 72-h incubation in SC-M1 cells. In COLO 205 cells,
      however, 5-MOP decreased the activity of NAT between 24 h and 72 h. The optimal
      concentrations of 5-MOP to induce decreased NAT activity in SC-M1 cells were 0.05
      mM to 25 mM. In COLO 205 cells, the data indicate that the higher the
      concentrations of 5-MOP, the higher the acetylation of AF; a promotion effect of
      NAT activity occured at a higher dose (50 mM) of 5-MOP and an inhibition effect
      occured at lower doses (0.05-0.5 mM) of 5-MOP, while concentrations of 5-25 mM of
      5-MOP showed no significant difference compared with the control regimen.
      CONCLUSION: The metabolic activity of NAT in the rat colon was higher than that
      in the rat stomach, and the results also showed a high degree of correspondence
      with SC-M1 cells and COLO 205 cells. 5-MOP more efficiently inhibited NAT
      activity in human stomach and colon tumor cell lines than in the stomach and
      colon of rats.

PMID- 16277024
TI  - Fast cancer uptake of 99mTc-labelled bombesin (99mTc BN1).
AB  - In human blood, breakdown of gastrin-releasing peptide and other bombesin-related
      peptides occurs in less than 15 min. This quick enzymatic cleavage might impair
      the diagnostic use of labelled bombesin (BN). 99mTc-labelled bombesin (99mTc BN1)
      was injected intravenously and dynamic uptake data were acquired for diagnosing
      26 cancers of different origin: 15 breast, 3 prostate, 5 colo-rectal, 1 pancreas,
      2 small cell lung cancers and 1 gastrinoma. Background subtracted tumour uptake
      data were plotted against time and fitted with known mathematical functions.
      Twenty-three out of 26 cancers showed rapid increase of radioactivity followed by
      a radioactivity plateau, with some oscillations around the average plateau value.
      The time to 80% of max activity (T80) was the reference parameter to measure and
      to compare the uptake speeds. The slowest T80 was 7 min in one T1b breast cancer,
      gastrinoma reached T80 in 5 min and node-positive prostate cancers in 2 min. N+
      breast cancers showed T80 at 3.62 +/- 0.75 min, N- breast cancers at 5.5 +/- 0.88
      min (p < 0.02). When all the tumours were considered, N+ tumours showed T80 at
      2.68 +/- 1.03 min and N- cancers at 5.5 +/- 0.82 min. In all the cancer types,
      the uptake of 99mTc BN was faster than 10 min. This result shows the ability of
      99mTc BN to image tumours. The faster uptake by N+ versus N- cancers probably
      depends on the higher blood flow in N+ cancers.

PMID- 16277025
TI  - Enhancement of the efficacy of chemotherapy with oxaliplatin plus 5-fluorouracil
      by pretreatment with IL-2 subcutaneous immunotherapy in metastatic colorectal
      cancer patients with lymphocytopenia prior to therapy.
AB  - The present study was carried out to evaluate the influence of a short-period IL
      2 administration on the efficacy of chemotherapy in metastatic colorectal cancer
      patients with pretreatment lymphocytopenia, which was defined as a lymphocyte
      count of less than 1500/mm3. The study included 144 consecutive metastatic
      colorectal cancer patients, who underwent chemotherapy with oxaliplatin plus 5
      fluorouracil. Lymphocytopenia was seen in 41/144 (28%) patients, who were
      randomized to receive chemotherapy alone or chemotherapy after a
      prechemoimmunotherapy with IL-2 (3 MIU twice/day for 3 consecutive days), whereas
      patients with a normal pretreatment lymphocyte count received only chemotherapy.
      A normalization of the lymphocyte number was achieved in 12/19 lymphocytopenic
      patients pretreated with IL-2. The objective tumor regression rate achieved in
      patients with a normal lymphocyte count prior to chemotherapy was significantly
      higher compared to that obtained in lmphocytopenic patients treated with
      chemotherapy alone (54/103 vs. 3/22, p < 0.01), whereas no significant difference
      occurred between patients with normal lymphocyte count and lymphocytopenic
      patients pretreated with IL-2 (54/103 vs. 8/19). This study confirms that
      pretreatment lymphocytopenia is associated with reduced efficacy of chemotherapy
      in metastatic colorectal cancer patients. Moreover, it suggests that pretreatment
      with IL-2 before the onset of chemotherapy may enhance the efficacy of
      chemotherapy in lymphocytopenic patients. Therefore, the administration of IL-2
      before the onset of chemotherapy to improve the immune status of cancer patients
      may be considered as a new chemoimmunotherapeutic combination, which may be
      recommended in the treatment of advanced cancer patients, particularly in those
      with cancer-related immune alterations.

PMID- 16277026
TI  - Effects of hormone replacement therapy on the main fatty acids of serum and
      phospholipids of postmenopausal women.
AB  - BACKGROUND: The anti-atherosclerotic effects of hormone replacement therapy (HRT)
      in postmenopausal women are partly mediated by improvement of the lipid and
      lipoprotein profiles. The present study aimed to investigate the effects of HRT
      on the main fatty acids of serum and phospholipids in postmenopausal women.
      PATIENTS AND METHODS: Serum samples of two groups of postmenopausal women,
      receiving either single oestrogen or in combination with progestogens, were
      analysed before and after a 6- month treatment period. RESULTS: Of the main serum
      fatty acids, there was a significant reduction in palmitic (p < 0.05) and
      arachidonic acids (p < 0.001), followed by an increase in oleic (p < 0.05) and
      linoleic acids (p < 0.05) in postmenopausal women receiving HRT compared to
      single oestrogen. The main fatty acids in phospholipids showed a similar pattern
      in those women. CONCLUSION: The above results demonstrate the beneficial effects
      of HRT in reducing the risk of cardiovascular disease through modification of the
      fatty acid profiles of postmenopausal women.

PMID- 16277027
TI  - Induction of apoptosis and necrosis by resistance modifiers benzazoles and
      benzoxazines on tumour cell line mouse lymphoma L5718 Mdr+cells.
AB  - Eighteen new fused heterocyclic compounds of benzazoles and benzoxazines were
      investigated for induction and inhibition of apoptosis on tumor cells (L5718,
      mouse lymphoma cell line containing the human mdr-1 gene). For evaluation of
      apoptosis, the cells were stained with FITC-labelled Annexin-V and propidium
      iodide and the results were analysed by flow cytometry. Nine of these substances
      were also checked for reversal of multidrug resistance. The reversal of multidrug
      resistance was determined by measuring the rhodamine-123 accumulation in the
      cancer cells. Rhodamine-123 shows a green fluorescence and its intracellular
      concentration correlates well with the inhibition of efflux pump activity. Three
      of the tested compounds, 5-(p-nitrobenzamido)-2-benzylbenzoxazole (BD-3), 6
      methyl-2-(o-chlorophenyl) benzoxazole (A-9) and 5-(p-nitrophenoxyacetamido)-2
      phenylbenzoxazole (D-30), showed an increased apoptotic effect on mouse lymphoma
      cells. Moreover, compounds BD-3, A-9 and 5-(2-thienylcarboxyamido)-2
      phenylbenzoxazole (D-24) also amplified the apoptosis effect of 12H
      benzo(a)phenothiazines (M-627). However, D-24, alone was not effective.
      Additionally, 2-(p-nitrobenzyl)benzoxazole (B-11), was also found to increase the
      apoptotic effect of M-627. On the other hand, 5-(p-nitrophenylacetamido)-2
      phenylbenzoxazole (D-7) showed an anti-apoptotic effect. No positive correlation
      was found between the increased drug accumulation effect and the programmed cell
      death induced by the compounds studied.

PMID- 16277028
TI  - Relationship of nm23 expression to proliferation and prognosis in malignant
      melanomas of the oral cavity.
AB  - Twenty-nine cases of oral melanomas were investigated for nm23 and Ki67 antigen
      expression, as well as for the fraction of tumour cells in S-phase, using
      immunohistochemical techniques and DNA cytophotometry. Nm23 expression was
      significantly reduced and Ki67 antigen expression increased in primary tumours
      with either lymph node or organ metastases in comparison to tumours without
      metastases. The percentages of Ki67 immunoreactive tumour cells and cells in S
      phase correlated positively with each other and negatively with the percentage of
      nm23-expressing cells. These data argue against a significant growth stimulatory
      function of the nm23H1 gene product nucleoside diphopshate kinase in the
      progression of oral melanomas. The functional relevance of nm23 in relation to
      increased proliferation and metastatic spread is discussed.

PMID- 16277029
TI  - Mott cell (Russell bodies) Barrett's oesophagitis.
AB  - The first case of Barrett's oesophagus with chronic inflammation having
      predominantly (> 50%) Mott cells, i.e. plasma cells with stored immunoglobulins,
      known as Russell bodies, is reported. Biopsies from two oesophagoscopies revealed
      similar changes, suggesting that the predominance of Mott cells is not a
      fortuitous event but a more long-lasting microscopic process. Periodic acid
      Schiff (PAS) stain ruled out Candida albicans and immunostains, plasma cell
      neoplasia. Mott cells were not present in biopsies from the gastric mucosa or the
      urinary bladder, suggesting that this phenomenon was not widespread but localized
      to the Barrett's mucosa. The retention of immunoglobulins (Russell bodies)
      suggests that the mechanism of protein transport in those plasma cells is
      incompetent, and that the proteins are neither degraded nor secreted, but remain
      stored in dilated cisternae. Increased awareness of the existence of this
      subgroup of Barrett's oesophagitis may result in similar cases being reported in
      the future.

PMID- 16277030
TI  - Preliminary studies on phenothiazine-mediated reversal of multidrug resistance in
      mouse lymphoma and COLO 320 cells.
AB  - The ability of phenothiazine derivatives to inhibit the transport activity of P
      glycoprotein in resistant mouse lymphoma and MDR/COLO 320 cells was studied. A
      rhodamine 123 efflux from the above-mentioned neoplastic cells in the presence of
      tested compounds was examined by flow cytometry. Two of the phenothiazine
      derivatives, namely perphenazine and prochlorperazine dimaleate, proved to be
      effective inhibitors of the rhodamine efflux. Other tested phenothiazine
      derivatives (promethazine hydrochloride, oxomemazine, methotrimeprazine maleate,
      trifluoropromazine hydrochloride, trimeprazine) also modulated the intracellular
      drug accumulation in both resistant cell lines, however, they exerted additional
      cytotoxic effects. The differences observed between the effects of the test
      compounds on intracellular drug accumulation could be the outcome of differences
      in phenothiazine's chemical structure, which is crucial for drug-cell membrane
      interactions. The results of this study provide information about a new group of
      compounds that offer promise in multidrug resistance reversal in tumor cells.

PMID- 16277031
TI  - Mucosa-associated lymphoid tissue lymphoma of the lacrimal gland--a case report.
AB  - MALT lymphoma of the ocular adnexa, an indolent B-cell lymphoma, rarely affects
      the lacrimal gland. The case of a 73-year-old man with ptosis and edema of the
      left upper eyelid, due to lacrimal gland swelling, is presented. Clinical
      evaluation and imaging examination led to excision biopsy. The mass
      histopathology, presenting organized lymphoid tissue, composed mainly of small B
      cells, accompanied by immunophenotypic characteristics, was compatible with MALT
      lymphoma. Treatment with monoclonal antibody against CD-20 achieved a successful
      long-term disease control (4 years). The diagnostic approach is described and the
      pathological features and clinical signs of this rare entity are discussed, based
      on recent literature. The indolent clinical course of this lymphoma, either
      remaining localized or disseminating to other mucosal sites, is a distinct
      characteristic affecting prognosis.

PMID- 16277032
TI  - [Vaccination--turned from its head to its feet].

PMID- 16277033
TI  - [Does vaccination cause disease?].
AB  - Not many inventions in medical history have influenced our society as much as
      vaccination. The concept is old and simple. When Edward Jenner published his work
      on cowpox, "variolation" was quite common. In this procedure, pus of patients
      with mild smallpox was transferred to healthy individuals. Meanwhile smallpox has
      been eradicated worldwide. Diseases such as poliomyelitis, diphtheria or tetanus
      almost disappeared in industrialized countries. The same happened with
      epiglottitis and meningitis due to Haemophilus influenzae type b (Hib) after
      vaccination against Hib was introduced in Switzerland in 1990. This success was
      possible because of routine vaccination. Immunization is a save procedure and
      adverse events are much lower than complications in the natural course of the
      prevented diseases. However vaccinations were accused to cause diseases
      themselves such as asthma, multiple sclerosis, diabetes mellitus, chronic
      arthritis or autism. Hitherto no large cohort study or case-control-study was
      able to proof responsibility of vaccines in any of these diseases. Public media
      are eager to publish early data from surveillance reports or case reports which
      are descriptive and never a principle of cause and effect. In large controlled
      trials there was no proof that vaccination causes asthma, hepatitis-B-vaccination
      causes multiple sclerosis or macrophagic myofasciitis, Hib-vaccination causes
      diabetes mellitus, rubella-vaccination causes chronic arthritis, measles-mumps
      rubella-vaccination causes gait disturbance or thiomersal causes autism. These
      results are rarely published in newspapers or television. Thus, many caring
      parents are left with negative ideas about immunization. Looking for the best for
      their children they withhold vaccination and give way to resurgence of
      preventable diseases in our communities. This must be prevented. There is more
      evidence than expected that vaccination is safe and this can and must be told to
      parents.

PMID- 16277034
TI  - [Vaccinations for journeys in the tropics].
AB  - Vaccinations are among the most important measures for maintaining the health
      during journeys in the tropics. Vaccination against Yellow Fever is compulsory
      for many African countries and for French Guyana. Vaccinations against
      Meningococcal Meningitis is compulsory for pilgrimage to Mecca. All travellers to
      tropical countries should be vaccinated against Hepatitis A, Diphtheria-Tetanus
      and against Measles for people below forty years of age. In addition vaccinations
      against Poliomyelitis, Typhoid Fever, Hepatitis B, Rabies and Japanese
      Encephalitis should be provided according to the duration, of the journey, the
      country of destination, and the risk of exposure.

PMID- 16277035
TI  - [Consequences of an unsufficient range of immunity in "pediatric" infectious
      diseases--example with measles].
AB  - From January to February 2005, the healthcare authorities of the Canton of Geneva
      were alerted to 15 cases of measles, in contrast to one single case in 2004. The
      adult status (17-44 years) of the affected persons years was unusual. Four were
      health care workers at the same hospital who were infected after contact with a
      44-year-old patient in a single night during his stay in the emergency room. The
      presumption that measles are only a paediatric disease had made the diagnosis
      difficult. None of all these adults was immune according to the actual
      recommendations. Despite a federal vaccine policy, repetition of recommendations,
      good results of available vaccines and reimbursement of the cost by health
      insurance companies, voluntary vaccination prevalence is too small in Switzerland
      to prevent the outbreak of epidemics. In contrast to the goals of the World
      Health Organization (WHO) and the Swiss Federal Office of Public Health, the
      country is unfortunately far from displaying a sufficiently high herd immunity to
      prevent health care-associated and economic damage by sporadic epidemics.

PMID- 16277036
TI  - [Vaccination against echinococcosis (?)].
AB  - Two species of the genus Echinococcus occur sympatrically in central Europe,
      namely Echinococcus multilocularis, the causative agent of alveolar
      echinococcosis (AE), and E. granulosus, resulting in cystic echinococcosis (CE)
      in humans. The endemic area of Europe demonstrates an annual incidence of 0.02 to
      1.4 new AE cases per 100000 inhabitants. The importance of the disease refers
      primarily to the high lethality observed in untreated cases. Therapeutically,
      radical surgical resection of hepatic lesions followed by continuous
      benzimidazole-therapy is anticipated. Recently, the strategic control of cystic
      echinococcosis in humans has considerably been improved by the development of an
      effective and efficient vaccine that will indirectly prevent humans from
      infection. The vaccine protects animal intermediate hosts (mainly farm
      ruminants), thus the lack of hydatid cysts in these animals will prevent dogs to
      become infected. This on the long-term will result in an abrogation of infection
      sources (Echinococcus eggs) for humans (and other intermediate hosts).
      Principally, it has been shown that a similar vaccination is also possible for E.
      multilocularis. Thus, a 14-3-3 and another Em95-vaccine have successfully been
      tested in the experimental murine model. As the parasite development mainly
      focuses on a wildlife cycle (wild rodents), a practical application of the
      vaccine can hardly be implemented. Nevertheless, AE is a very severe disease in
      humans, therefore one should discuss about the feasibility and the health
      economic impact of large-scale vaccination of humans living in areas of high
      endemicity and thus being at high infection risk.

PMID- 16277037
TI  - [HIV-1 vaccination--is there hope?].
AB  - The HIV pandemic continues. Today the number of HIV-infected people is estimated
      to be 39.4 million. Despite huge efforts it is unlikely that there will be an
      efficient HIV vaccine available in the near future. Until now, only two phase III
      HIV vaccination trials have been performed in man. However, transmission could
      not be prevented. The hurdle for a rational approach to generate a vaccine is the
      still incomplete knowledge about HIV pathogenesis and the high rate of mutations
      of HIV. In this review we discuss the distinct aspects of the immune response,
      which could be exploited for HIV vaccine strategies and describe current vaccine
      approaches.

PMID- 16277039
TI  - Disaster preparedness task force interim report.

PMID- 16277038
TI  - Medicare payment changes portend trouble.

PMID- 16277040
TI  - An outstanding overview of health care in Maryland.

PMID- 16277041
TI  - Retreat to advance.

PMID- 16277042
TI  - Emotional intelligence and violence.

PMID- 16277043
TI  - Revisiting the community hospital approach to child abuse.

PMID- 16277044
TI  - Maryland's child advocacy centers.

PMID- 16277045
TI  - Prevention of youth violence.
AB  - Youth violence is widely recognized as a major public health problem. Concern
      over the number of youth affected by violence in their homes, communities, and in
      schools has precipitated considerable discussion in the popular press and in
      professional journals. This article reviews recent activity to reduce youth
      violence with an emphasis on activity taking place in Maryland. The number of
      youth murdered or exposed to violence in Maryland remains too high. Although most
      of our youth are resilient, they are not unaffected by the violence that
      surrounds them. Exposure to violence places children at high risk for a variety
      of emotional and behavioral problems, such as poor academic performance, anxiety,
      post-traumatic stress disorder, and inadequate socialization and development.

PMID- 16277046
TI  - The impact of violence in video games.

PMID- 16277047
TI  - Violence against self: self-mutilation syndromes.

PMID- 16277048
TI  - Firearm suicide in Maryland: characteristics of older versus younger suicide
      victims.

PMID- 16277049
TI  - Domestic violence--more than bruises and broken bones.

PMID- 16277050
TI  - MedChi's response to the challenge of helping victims.

PMID- 16277051
TI  - Elder abuse.

PMID- 16277052
TI  - The burden of violence and injuries in Maryland.

PMID- 16277053
TI  - Are we our brothers' (and sisters') keepers?

PMID- 16277055
TI  - [Once upon a time...].

PMID- 16277056
TI  - [Is a reformation of the medical training worthwhile? The quality of the Hamburg
      curriculum under the old and the new board certification law].
AB  - This paper presents the results of the evaluation of a new undergraduate
      curriculum at the Medical Faculty of Hamburg University. This curriculum is based
      on the new law on medical board certification of 2002, and was tested for the
      first time in the summer term of 2004. The results were compared with those
      obtained under the previous law. The data show a substantial increase in student
      subjective learning effectiveness and satisfaction with the new program. The
      reasons discerned were the increased practice orientation of the program, the
      problem-oriented seminars, and the increased motivation of the teaching staff.

PMID- 16277057
TI  - [Prevention and aging--topics for medical training and continuing education?
      Analysis of current and future situations].
AB  - Due to the current demographic changes, prevention, health promotion, and aging
      are key topics for future healthcare delivery systems. Interviews with physicians
      and analyses of the medical training and continuing education show substantial
      deficits within these areas. The restructuring of the medical training in
      Germany, together with the introduction of a new boardcertification ordinance,
      offers the opportunity to strengthen these topics.

PMID- 16277058
TI  - [First mandatory training in evidence-based medicine in the Medical Education
      Programme of the University of Frankfurt].
AB  - Changes in the German medical licensing law in 2002 demanded the inclusion of
      sound scientific knowledge and practical skills in the medical education
      programme for undergraduates. The universities were given ample autonomy to
      implement this goal, so that subjects not yet included in the curricula, such as
      Evidence-based Medicine (EbM), could now be integrated in the study course.
      Hence, in 2003 the Medical Faculty of the Johann Wolfgang Goethe University,
      Frankfurt/Germany implemented (as first institution) a mandatory clinical
      training in EbM for third-year medical students. The content and structure of the
      seminar are based on the "Curriculum EbM" of the German Network of Evidence-Based
      Medicine. This project is conducted exclusively by intern medical students with
      previous training in teaching skills and specific knowledge. The seminar is
      integrated in the interdisciplinary field "Epidemiology, biostatistics, and
      informatics". The four-day seminars consist of lectures and small-group teaching
      based on Internet search of medical information as well as on the critical
      appraisal of studies that deal with therapeutic and diagnostic problems; the self
      evaluation of the information-retrieval process is also included. Special
      importance is attached to the need of scrutinising published medical information.
      The grades are based on seminar-oriented tests as well as on end-of-term
      examinations. The Frankfurt project shows that EbM can be easily implemented in
      medical undergraduate courses.

PMID- 16277059
TI  - [Perception of continuous medical education by primary care physicians].
AB  - The enormous increase of specific medical knowledge has become a growing
      challenge also for general practitioners (GPs) in their daily routine. In this
      study, GPs practising in Berlin were asked about their experience with Continuous
      Medical Education (CME). The evaluation of this survey may help planning future
      qualification courses. Thirty GPs from Berlin (14 females, 16 males) participated
      in a qualitative survey and were interviewed about their experience with and the
      use of CME programmes offered. The interviews performed were summarised,
      structured, and analysed according to the qualitative analysis of content by
      Mayring. The GPs considered lack of time to be the general impediment to their
      further professional development. The patient-oriented communication with
      specialised colleagues during working hours was considered an important tool of
      CME. Traditional educational means, for example professional journals, were
      appreciated because of their flexible use in terms of time and location. Due to
      the lack of time, GPs may favour types of CME that can be used flexibly. The
      implementation of professional medical networks between GPs and specialty
      consultants may have a major impact on future CME programmes.

PMID- 16277060
TI  - ["Truth at the bedside"--continuing medical education and breaking bad news].
AB  - INTRODUCTION: Discussions with seriously-ill patients are part of the physicians'
      tasks. These discussions demand good communication skills. In this paper we
      present the concept of a postgraduate course for physicians on ethics and
      breaking bad news, as well as the results of the course evaluation. METHODS:
      Questionnaire distributed before and immediately after the course using closed
      ended questions and Likert scales. RESULTS: 37 physicians (response rate: 84.1%)
      from seven specialties completed the questionnaires. Twenty-eight respondents
      (75.6%) had been involved in breaking bad news more than 5 times per month.
      Approximately half of the respondents (N = 18; 48.6%) rated the discussions on
      the limits of curative treatment as particularly difficult communication
      situations. With one exception, all physicians denied the existence of guidelines
      on breaking bad news in their institutions. Compared with the beginning of the
      course, the respondents rated their communication skills to be improved at the
      end of the course. Positive evaluations were obtained for practice relevance,
      teaching methods, and organisation of the course. CONCLUSION: The interest in
      this optional postgraduate course and the feedback of the participants indicate
      the necessity of professional training on difficult communication situations. The
      self-rating of improved communication skills may be interpreted as a positive
      effect of the course. Observational studies are required to confirm the effects
      of the training.

PMID- 16277061
TI  - [Long-term benefits of a postgraduate programme in clinical epidemiology. The
      study programme "clinical evaluation" of the University of Marburg].
AB  - In 1997 the first Clinical Epidemiology Programme in Germany was founded at the
      University of Marburg. This has been a part-time programme of six months'
      duration for young medical researchers interested in study planning, conduct and
      analysis. We report the results of focus group evaluations undertaken at the end
      of each programme which is held every year. We also surveyed former participants
      by phone to assess long-term effects of the programme. Overall, according to
      participants' feedback the programme has been a success. In particular,
      competences in study planning and critical appraisal were considered useful.
      However, participants reported difficulties implementing their newly gained
      knowledge and skills within their home departments. Postgraduate programmes of
      this kind catalyze the establishment of clinical research at German University
      Medical Centres.

PMID- 16277062
TI  - The effects of contemporary and alternative medicine on healthcare and dentistry.

PMID- 16277063
TI  - Trading an explorer for a pitchfork.

PMID- 16277064
TI  - Dental implant and bone graft markets to approach 3.5 billion dollars in 2010.

PMID- 16277065
TI  - ADA Foundation seeks proposals for grants up to 25,000 dollars.

PMID- 16277066
TI  - "Na-no, na-no" bacteria?

PMID- 16277067
TI  - Seventh-generation bonding materials as cavity liners: scientific rationale and
      clinical technique.

PMID- 16277068
TI  - Suturing for surgical success.

PMID- 16277069
TI  - Retrofitting crowns under an existing removable clasp partial denture.

PMID- 16277070
TI  - Mini dental implants: immediate gratification for patient and provider.

PMID- 16277071
TI  - Intracanal heating of sodium hypochlorite solution: an improved endodontic
      irrigation technique.

PMID- 16277072
TI  - Selecting the right dental laboratory for your practice.

PMID- 16277073
TI  - Treatment planning multiphase, combination restorations for full-mouth
      rehabilitation.

PMID- 16277074
TI  - The use of colored components as fillings in deciduous teeth.

PMID- 16277075
TI  - Temporization: freehand artistry defining clinical success.

PMID- 16277076
TI  - Anterior direct composite: easy as 1-2-3.

PMID- 16277077
TI  - The new-patient interview.

PMID- 16277078
TI  - The reality of the paperless dental office.

PMID- 16277079
TI  - Buyers guide to all-ceramic systems.

PMID- 16277080
TI  - Buyers' guide to shade-matching systems.

PMID- 16277081
TI  - Buyers' guide to diamonds and burs. So, what's new in burs?

PMID- 16277083
TI  - [Idiopathic Parkinson syndrome. Main symptoms: tremor, rigor, akinesis (postural
      instability].

PMID- 16277084
TI  - [The role of dopaminagonists in the treatment of Parkinson's disease].
AB  - Dopamine agonists play an important role in the treatment of early Parkinson's
      disease, either as monotherapy or in combination with levodopa. Initial treatment
      with dopamine agonists has been found to postpone or prevent from motor
      fluctuations and dyskinesias. Dopamine agonists have also been shown to be
      significantly effective in the treatment of motor oscillations and dyskinesias
      related to chronic levodopa treatment. The "new" dopaminagonists pergolide,
      cabergoline, ropinirole and pramipexole tend to be more effective than
      bromocriptine. Due to side-effects dopamine agonists are mainly used in subjects
      younger than 70 to 75 years.

PMID- 16277085
TI  - [Autonomic dysregulations in Parkinson's syndrome].
AB  - For a long time, autonomic dysregulations in Parkinson's syndrome have been
      underrated as to their incidence and severity. Meanwhile, we know about their
      occurrence in the early stage of illness and that they do affect all patients in
      different ways and varyingly degrees. Patients should thus be interviewed and
      tested accordingly, and have treatment as needed. Cardiovascular,
      gastrointestinal and urogenital symptoms are most commonly found. However, any
      organic system can be involved.

PMID- 16277086
TI  - [Cognitive disorder in Parkinson's disease].
AB  - Over the course of Parkinson's disease, a substantial percentage of patients not
      only develop motor und vegetative disorders, but also significant cognitive
      deficits that can, in isolated cases, take on the proportions of dementia.
      Additionally, affective and emotional dysregulations extending to depressive
      disorders may become manifest. These impairments can be explained by the
      underlying neuropathology and the Parkinson-associated transmitter imbalances as
      well as by the changes this disease causes in the patients' daily lives.
      According to Gifford and Cummings [21], up to 75 percent of patients with
      moderate to severe dementia are not diagnosed by their general practitioners;
      this number proving much higher in patients with mild cognitive impairments and
      affective and emotional problems. Due to the masking symptoms of a Parkinson's
      condition, it can be assumed that these numbers are probably even higher in this
      patient group. Accordingly, cognitive, affective and emotional disorders should
      be included as an integral part of Parkinson's disease diagnostics.

PMID- 16277087
TI  - [Alert thanks to peppermint odor?].

PMID- 16277088
TI  - [Alexander the Great an alcoholic?--Regarding retrospective diagnoses in patients
      in antiquity].

PMID- 16277089
TI  - [Combination of professional and personal life].

PMID- 16277090
TI  - [Rhone-Alps region: meeting current needs].

PMID- 16277091
TI  - A short impact of epidemiological features of colorectal cancer in Iran.
AB  - AIMS AND BACKGROUND: The incidence of colorectal cancer varies from one country
      to another although the variation is not much different in neighboring countries.
      Even in one country there is no relevant variation in incidence from one province
      to another. A study of different provinces in a vast developing country, Iran,
      was performed to determine the incidence of colorectal cancer. METHODS:
      Information from cancer registries of four provinces in the north, north-west and
      central-south of Iran regarding colorectal cancer was gathered for analysis. A
      total of 1628 cases with colorectal cancer in a total population of 6,435,549 was
      identified. RESULTS AND CONCLUSIONS: In all provinces, there were more male than
      female patients with colorectal cancer. The study also showed that the incidence
      of the disease in young patients was higher than expected. Except for Israel
      because of genetic factors, these provinces showed one of the highest ASR among
      Asian countries. This finding probably indicates more westernization in the
      Iranian diet with a genetic influence. Some social habits including dietary and
      tobacco smoking may also influence the incidence of colorectal cancer in the
      Iranian population. Community-related risk factors need further investigation,
      especially in the high-risk Northern part of the country.

PMID- 16277092
TI  - Concurrent 5-fluorouracil, mitomycin C and radiation with or without
      brachytherapy in recurrent cervical cancer: a scoring system to predict clinical
      response and outcome.
AB  - AIMS AND PURPOSE: This is a prospective, phase II study aimed to evaluate the
      effect of concurrent 5-fluorouracil, mitomycin C, and radiation with or without
      brachytherapy on the clinical outcome of a series of recurrent cervical cancer
      patients and to determine the prognostic impact of a subset of factors. METHODS:
      Thirty-three patients with locally recurrent, non-metastatic cervical cancer
      received external beam radiation (4-week split course: 23.4 + 23.4 Gy) plus two
      courses of concomitant chemotherapy (5-fluorouracil, 96-h continuous infusion,
      days 1-4, 1 g/m2/day; mitomycin C, 10 mg/m2, bolus i.v., day 1). Twelve patients
      with vaginal recurrence (36.4%) underwent endocavitary low-dose rate
      brachytherapy boost (20-25 Gy); 11 patients with lateral pelvic recurrence
      (33.3%) received external beam radiation boost (14-20 Gy). RESULTS: Fourteen
      complete responses (42.4%), 7 partial responses (21.2%), 5 disease stabilizations
      (15.1%) and 7 progressions (21.2%) were obtained. After a median follow-up of 34
      months (range, 6-127), overall actuarial 3-year survival, progression-free
      survival and local progression-free survival were 59.7%, 48.1% and 51.7%,
      respectively. Patients with vaginal recurrence of less than 4 cm and negative
      lymph nodes proved to respond best to the treatment. Two patients (6.1%)
      experienced hematologic grade 3 toxicity. One patient had grade 3 intestinal
      toxicity (3.0%). No patient had major skin or urological acute toxicity. Severe
      late toxicity was infrequent. Three patients had prolonged leukopenia (9.0%).
      Four patients showed severe vaginal stenosis (12.1%). A clinical score of 0 to 1
      was assigned to each patient on the basis of the absence (score = 0) or presence
      (score = 1) of any of the following prognostic factors: time between surgery and
      recurrence shorter than 12 months, pelvic wall site of recurrence, positive lymph
      nodes, hemoglobin < 11 g/dL. Using this system, it was clear that patients with a
      low total score had a significantly better outcome (clinical remission, 51% of
      patients with a score < or = 2 vs 12% of patients with a score > 2, P = 0.06),
      local control of the disease (65% vs 20% after 3 years, P = 0.001,) and overall
      survival (75% vs 30% after 3 years, P = 0.032). CONCLUSIONS: Our data suggest
      that this combined modality therapy was relatively well tolerated and resulted in
      reasonable local control and survival. The scoring system proved to be helpful to
      identify patients with the greatest chance of benefiting from the treatment.
      Further studies are probably needed to salvage the other patients, whose
      prognosis remains severe.

PMID- 16277093
TI  - Expression of p53 protein and DNA flow cytometry in gastric adenocarcinoma:
      implications in patients treated with adjuvant etoposide, adriamycin and
      cisplatin.
AB  - AIMS AND BACKGROUND: We evaluated the prognostic value of p53 protein, DNA
      content and S-phase fraction in patients with adenocarcinoma of the stomach or
      the gastroesophageal junction treated with adjuvant etoposide, doxorubicin and
      cisplatin. METHODS AND STUDY DESIGN: Thirty-five consecutive patients with stage
      II or III gastric or gastroesophageal junction adenocarcinoma treated with at
      least two cycles of adjuvant etoposide, doxorubicin and cisplatin after curative
      gastric resection were included. The expression of p53 protein was determined by
      immunohistochemistry and DNA content by flow cytometry. The presence of p53
      expression and DNA content was compared with clinicopathological features.
      RESULTS: Median age was 54 years (range, 31-71). P53 expression was detected in
      42.9% (15 of 35) of gastric cancer tissues of the patients. Aneuploidy was
      observed in 31.4% of patients, and S-phase fraction was more than 10% in 22.9%.
      P53 immunoreactivity (33.3% vs 47.8%) was more common in advanced disease. There
      was no association among p53 immunoreactivity, DNA content and S-phase fraction.
      We also found no significant relationship between p53 immunoreactivity, DNA
      content, S-phase fraction or other clinicopathological parameters. In univariate
      analysis, the involvement of lymph nodes was a significant predictor of a poor
      outcome (P = 0.001). Also, p53-positive patients had a poor survival close to the
      level of significance (P = 0.051). Likewise, p53 immunoreactivity (P = 0.0071),
      in addition to lymph node involvement (P = 0.0016), were the independent
      prognostic factors in multivariate analysis. CONCLUSIONS: This trial supports the
      results of previous reports that p53 immunoreactivity is a prognostic factor for
      patients with adenocarcinoma of stomach or gastroesophageal junction treated with
      adjuvant chemotherapy.

PMID- 16277094
TI  - Irinotecan and oxaliplatin combination, as second-line treatment, in
      fluoropyrimidine-pretreated advanced colorectal cancer. A phase II study by the
      Hellenic Cooperative Oncology Group (HeCOG).
AB  - BACKGROUND: The management of patients with fluoropyrimidine-resistant advanced
      colorectal cancer remains Investigational. Irinotecan and oxaliplatin have proved
      effective in first-line treatment in combination with 5-fluorouracil. STUDY
      DESIGN: From February 1998 to September 2002, 34 patients with 5-fluorouracil
      pretreated advanced colorectal cancer were enrolled in the study. Median age was
      67 years (range, 32-76) and median performance status was 1. Twenty-one patients
      had multiple liver metastases. Other sites of disease included lungs, abdomen,
      pelvis, lymph nodes, bones and skin. They received six 28-day cycles of
      oxaliplatin (85 mg/m2 in a 2-h infusion on days 1 and 15) and irinotecan (80
      mg/m2 in a 30-minute infusion on days 1, 8 and 15 immediately following
      oxaliplatin). RESULTS: Thirteen patients (39%) completed treatment. The most
      common grade Ill-lV toxicities were diarrhea (27%), anemia (6%), neutropenia
      (18%), alopecia (6%) and peripheral neuropathy (6%). Thirteen patients (39%)
      received G-CSF support, and there were 2 episodes of febrile neutropenia. There
      were no treatment-related deaths. Six patients (18%) had a partial remission and
      another 11 (33%), disease stabilization. There were no complete remissions.
      Median time to progression was 6.6 months (range, 0.8-20.1) and median survival
      10.6 months (range, 0.8-52.9). CONCLUSIONS: Irinotecan and oxaliplatin
      combination has modest activity as second line treatment of 5-fluorouracil
      resistant advanced colorectal cancer. Further research is warranted for the
      development of more effective and less toxic regimens in this setting.

PMID- 16277095
TI  - Dose-finding study of weekly docetaxel plus estramustine in patients with hormone
      refractory metastatic prostate cancer.
AB  - OBJECTIVE: The aim of this phase I study was to find the maximum tolerated dose
      of weekly docetaxel in association with estramustine in hormone-refractory
      prostate cancer. METHODS: Eleven patients with hormone-refractory prostate cancer
      were treated with escalating weekly doses of docetaxel (level I, 3 patients, 30
      mg/m2; level II, 3 patients, 35 mg/m2, level III, 3 patients, 40 mg/mz; level IV,
      2 patients, 45 mg/m2) associated with fixed dosage of estramustine (840 mg/day).
      RESULTS: In level I, there was only one episode of grade 3 neutropenia; grade 1
      nausea and vomiting were registered in 1 patient; in 1 patient mild edema of the
      lower limbs was noted. In level II, grade 2 stomatitis and grade 1 sensory
      symptoms occurred in 1 patient, and grade 1 edema in 1 case. In level Ill, grade
      2 edema was noted in 2 patients, damage to nails in 1 patient, asthenia in 1
      patient, grade 1 neuropathy in 2 patients, and grade 1 nausea in 1 patient. In
      level IV, grade 2 edema was present in 1 patient, grade 3 edema in 1 patient,
      changes with fall of nails and grade 2 erythema of face in 2 patients, asthenia
      in 2 patients, grade 1 neuropathy in both patients. Nine patients had a more than
      a 50% decrease in PSA after 2 cycles of therapy. CONCLUSIONS: The results of the
      study suggest a good tolerability of weekly 35 Mg/m2 docetaxel in hormone
      refractory prostate cancer in association with estramustine.

PMID- 16277096
TI  - Different clinical features of primary and secondary tumors in patients with
      multiple malignancies.
AB  - Clinical features of the first and second primaries in patients with multiple
      malignancies have not been extensively studied. We compared patient and treatment
      characteristics of the primary malignancy in 48 consequent multiple primary
      cancer patients with those of the second primary in the same cohort. The second
      primaries comprised fewer breast cancers; 29.2% of primaries as opposed to 10.4%
      of second tumors were breast cancer (P = 0.049). In addition, primary tumors
      tended to be at a lower TNM stage than secondary tumors (P = 0.060). The median
      overall survival after the diagnosis of the first primary for the whole cohort
      was 22.3 years (95% CI, 2.0-42.5) and the median time to presentation of the
      second malignancy was 38 months after the diagnosis of the first primary (range,
      0 to 384). Therefore, the prognosis of cancers in the multiple malignancy group
      appears to be good and they appear to have an indolent clinical behavior. Thus,
      we recommend a long screening time for secondary tumors after a curative
      treatment in patients with common cancers, taking into account the different
      occurrence patterns of second primaries with respect to first primaries.

PMID- 16277097
TI  - Locally advanced breast cancer in the elderly: curettage mastectomy.
AB  - AIMS AND BACKGROUND: Locally advanced breast tumor represents 5-20% of new cases
      diagnosed every year. The purpose of this study was to report our experience and
      to compare it with the literature. METHODS: From 1998 to 2003 at the Molinette
      Hospital in the Turin University Third Division of General Surgery, there were 34
      cases of breast cancer in older women (between 70 and 94 years of age), 14 of
      which (41.18%) were locally advanced breast tumor. We evaluated the type of
      surgical intervention and anesthesia used, muscular invasion, the presence of
      receptors positive to estrogens and progesterone, the operative mortality, the
      percentage of local-regional recurrence, and relapses after a period of time.
      RESULTS: Among the patients with locally advanced breast tumor, 21.43% (3/14)
      were at stage IIIA and 78.57% (11/14) at stage IIIB. In 14.29% (2/14) of the
      cases, Patey's radical mastectomy was performed, in 57.14% (8/14) Halsted's
      radical mastectomy, and in 28.57% (4/14) a simple mastectomy with the removal of
      the fascia of the major pectoral muscle. Three (21.43%) patients underwent a
      second intervention for local-regional disease. None of the patients had distant
      metastasis in the first 2 years after the operation. Mortality after 2 years was
      23.1% (3/13). None of the patients who underwent surgery had adjuvant therapy,
      usually because it was refused by the patients themselves or their families. All
      the negative and positive hormone receptor patients received tamoxifen.
      CONCLUSIONS: Locally advanced breast tumors are frequent in elderly women. In the
      past, there has been a tendency to surgical under-treatment. As regards locally
      advanced breast tumor, curettage operations represent the only possibility to
      improve the quality of life of the elderly. These should be performed after
      carefully evaluating a series of variables in the general and local condition of
      the patient, the aggressiveness of the intervention and the life expectancy.

PMID- 16277098
TI  - Re-irradiation of brain metastases and metastatic spinal cord compression:
      clinical practice suggestions.
AB  - The recent improvements of therapeutic approaches in oncology have allowed a
      certain number of patients with advanced disease to survive much longer than in
      the past. So, the number of cases with brain metastases and metastatic spinal
      cord compression has increased, as has the possibility of developing a recurrence
      in areas of the central nervous system already treated with radiotherapy.
      Clinicians are reluctant to perform re-irradiation of the brain, because of the
      risk of severe side effects. The tolerance dose for the brain to a single course
      of radiotherapy is 50-60 Gy in 2 Gy daily fractions. New metastases appear in 22
      73% of the cases after whole brain radiotherapy, but the percentage of
      reirradiated patients is 3-10%. An accurate selection must be made before giving
      an indication to re-irradiation. Patients with Karnofsky performance status > 70,
      age < 65 years, controlled primary and no extracranial metastases are those with
      the best prognosis. The absence of extracranial disease was the most significant
      factor in conditioning survival, and maximum tumor diameter was the only variable
      associated with an increased risk of unacceptable acute and/or chronic
      neurotoxicity. Re-treatment of brain metastases can be done with whole brain
      radiotherapy, stereotactic radiosurgery or fractionated stereotactic
      radiotherapy. Most patients had no relevant radiation-induced toxicity after a
      second course of whole brain radiotherapy or stereotactic radiosurgery. There are
      few data on fractionated stereotactic radiotherapy in the re-irradiation of brain
      metastases. In general, the incidence of an "in-field" recurrence of spinal
      metastasis varies from 2.5-11% of cases and can occur 2-40 months after the first
      radiotherapy cycle. Radiation-induced myelopathy can occur months or years (6
      months-7 years) after radiotherapy, and the pathogenesis remains obscure. Higher
      radiotherapy doses, larger doses per fraction, and previous exposure to radiation
      could be associated with a higher probability of developing radiation-induced
      myelopathy. Experimental data indicate that also the total dose of the first and
      second radiotherapy, interval to re-treatment, length of the irradiated spinal
      cord, and age of the treated animals influence the risk of radiation-induced
      myelopathy. An alpha/beta ratio of 1.9-3 Gy could be generally the reference
      value for fractionated radiotherapy. However, when fraction sizes are up to 5 Gy,
      the linear-quadratic equation become a less valid model. The early diagnosis of
      relapse is crucial in conditioning response to re-treatment.

PMID- 16277099
TI  - Perioperative hyperfractionated high-dose rate brachytherapy combined with
      external beam radiotherapy in the treatment of soft tissue sarcomas.
AB  - AIMS AND BACKGROUND: Low-dose rate brachytherapy alone or in combination with
      external beam radiotherapy represents a well-established adjuvant treatment in
      soft tissue sarcomas following surgical resection. The experience with high-dose
      radiotherapy in this indication is limited. The purpose of our study was an
      evaluation of the viability of perioperative hyperfractionated high-dose rate
      brachytherapy in combination with external beam radiotherapy for primary and
      recurrent soft tissue sarcomas. PATIENTS AND METHODS: From February 1998 through
      June 2002, 10 adult patients with soft tissue sarcomas were treated by
      interstitial perioperative high-dose rate brachytherapy and external beam
      radiotherapy. TNM classification was pT2bpN0pM0 in 9 patients and pT1bpN0pM0 in 1
      patient. Grade of differentiation was G1 (2 patients), G2 (n = 1), G3 (n = 5), G4
      (n = 2). Surgical margins were negative in 7 cases, close in 2 cases and positive
      in 1 case. The tumor was localized in an extremity in all cases.
      Hyperfractionation 3 Gy twice daily at 10 mm from the plane of sources was used
      for brachytherapy, with total doses 18-30 Gy. The patients received external beam
      radiotherapy with doses 40-50 Gy after brachytherapy. Follow-up periods were
      between 24-71 months (median, 46). RESULTS: Local control of the disease was
      achieved in all 10 patients. Distant metastases occurred in 2 cases. One patient
      was disease free after salvage surgery and chemotherapy, and one patient died of
      lung disease progression 14 months after brachytherapy. In one case, subcutaneous
      fistula occurred after radiotherapy and was cured by an excision. Six patients
      experienced grade 1 or 2 fibrosis and 1 case a mild peripheral neuropathy was
      recorded. CONCLUSIONS: Our study on a small number of patients suggests that
      perioperative hyperfractionated high-dose rate brachytherapy with doses 8 x 3 Gy
      in combination with external beam radiotherapy 40-50 Gy is a promising method to
      achieve high biological doses in the postoperative radiotherapy of soft tissue
      sarcomas without severe late morbidity and warrants further research.

PMID- 16277100
TI  - Prostate brachytherapy with iodine-125 seeds: radiation protection issues.
AB  - AIMS AND BACKGROUND: Brachytherapy for prostate cancer by means of permanently
      implanted 125I sources is a well established procedure. An increasing number of
      patients all over the world are treated with this modality. When the technique
      was introduced at our institution, radiation protection issues relative to this
      technique were investigated in order to comply with international recommendations
      and national regulations. Particular attention was paid to the need for patient
      shielding after discharge from hospital. METHODS: The effective and equivalent
      doses to personnel related to implantation, the effective dose to patient
      relatives as computed by a developed algorithm, the air kerma strength values for
      the radioactive sources certified by the manufacturer compared with those
      measured by a well chamber, and the effectiveness of lead gloves in shielding the
      hands were evaluated. RESULTS: The effective dose to the bodies of personnel
      protected by a lead apron proved to be negligible. The mean equivalent doses to
      the physician's hands was 420 microSv for one implant; the technician's hands
      received 65 microSv. The mean air kerma rate measured at the anterior skin
      surface of the patient who had received an implant was 55 microGy/h (range, 10
      115) and was negligible with lead protection. The measured and certified air
      kerma strength for125I seeds in RAPID Strand corresponded within a margin of +/-
      5%. The measured attenuation by lead gloves in operative conditions was about
      80%. We also defined the recommendations to be given to the patient at discharge.
      CONCLUSIONS: The exposure risks related to brachytherapy with 125I to operators
      and public are limited. However, alternation of operators should be considered to
      minimize exposure. Patient-related measurements should verify the dose rate
      around the patient to evaluate the need for shielding and to define appropriate
      radiation protection recommendations.

PMID- 16277101
TI  - Intraoperative radiotherapy (IORT) for breast cancer using the Intrabeam system.
AB  - INTRODUCTION: Intraoperative radiotherapy (IORT) with low-energy X-rays (30-50
      KV) is an innovative technique that can be used both for accelerated partial
      breast irradiation (APBI) and intraoperative boosting in patients affected by
      breast cancer. Immediately after tumor resection the tumor bed can be treated
      with low-distance X-rays by a single high dose. Whereas often a geographic miss
      in covering the boost target occurs with external beam boost radiotherapy (EBRT),
      the purpose of IORT is to cover the tumor bed safely. This report will focus on
      the feasibility and technical aspects of the Intrabeam device and will summarize
      our experience with side effects and local control. MATERIALS AND METHODS:
      Between February 2002 and June 2003 57 breast cancer patients, all eligible for
      breast conserving surgery (BCS), were treated at the Mannheim Medical Center with
      IORT using the mobile X-ray system Intrabeam. The patient population in this
      feasibility study was not homogeneous consisting of 49 patients with primary
      stage I or II breast cancer, seven with local recurrence after previous EBRT and
      one with a second primary in a previously irradiated breast. The selection
      criteria for referral for IORT included tumor size, tumor cavity size, margin
      status and absence of an extensive intraductal component. The previously
      irradiated patients with local recurrences and 16 others received IORT as single
      modality. In all other cases IORT was followed by EBRT with a total dose of 46 Gy
      in 2-Gy fractions. The intraoperatively delivered dose after tumor resection was
      20 Gy prescribed to the applicator surface. EBRT was delivered with a standard
      two-tangential-field technique using linear accelerators with 6- or 18-MV
      photons. Patients were assessed every three months by their radiation oncologist
      or surgeon during the first year after treatment and every six months thereafter.
      Breast ultrasound for follow-up was done every six months and mammographies once
      yearly. Acute side effects were scored according to the CTC/EORTC score and late
      side effects according to the Lent-Soma classification. RESULTS: Twenty-four
      patients received IORT only; eight patients because they had received previous
      radiotherapy, 16 because of a very favorable risk profile or their own
      preference. Thirty-three patients with tumor sizes between 1 and 30 mm and no
      risk factors were treated by IORT as a boost followed by EBRT. The Intrabeam
      system was used for IORT. The Intrabeam source produces 30-50 KV X-rays and the
      prescribed dose is delivered in an isotropic dose distribution around spherical
      applicators. Treatment time ranged between 20 and 48 minutes. No severe acute
      side effects or complications were observed during the first postoperative days
      or after 12 months. One local recurrence occurred 10 months after surgery plus
      IORT followed by EBRT. In two patients distant metastases were diagnosed shortly
      after BCS. DISCUSSION: IORT with the Intrabeam system is a feasible method to
      deliver a single high radiation dose to breast cancer patients. As a preliminary
      boost it has the advantage of reducing the EBRT course by 1.5 weeks, and as APBI
      it might be a promising tool for patients with a low risk of recurrence. The
      treatment is well tolerated and does not cause greater damage than the expected
      late reaction in normal tissue.

PMID- 16277102
TI  - P53 alteration in oral tongue cancer is not significantly associated with age at
      diagnosis or tobacco exposure.
AB  - AIMS AND BACKGROUND: The tumor suppressor gene P53 is mutated in almost half of
      head and neck cancers. The current work assessed the prognostic significance of
      P53 alteration in patients with squamous cell carcinoma of the oral tongue
      treated with a curative intent, its association with age at diagnosis (using 45
      years as a cut point), and risk exposure as defined by tobacco and/or alcohol
      consumption. METHODS: P53 alteration was determined immunohistochemically in 45
      patients with tongue cancer treated with a curative intent. RESULTS: P53
      alteration occurred in 20 of 45 tumors (44%) and was more common among younger
      patients (58% versus 36% for younger versus older patients, respectively) and
      those lacking tobacco/alcohol exposure (53% versus 40% for "no-risk" and "risk"
      groups, respectively), but the differences were not statistically significant.
      With a median follow-up of 56 months, 5-year progression-free survival rates were
      48% and 66% in patients with and without P53 detection, respectively (P = 0.22).
      CONCLUSIONS: Despite a trend of a younger age at diagnosis in P53-altered tumors,
      results did not reach statistically significant differences. A trend of a worse
      clinical outcome with P53 alteration was noted.

PMID- 16277103
TI  - Vacuum-assisted core biopsy (Mammotome) for the diagnosis of non-palpable breast
      lesions: four-year experience in an Italian center.
AB  - AIMS AND BACKGROUND: Microinvasive biopsy techniques are increasingly employed in
      the diagnostic assessment of non-palpable breast lesions (NPBLs). This study
      reports the four-year experience of an Italian surgical center in the evaluation
      of the diagnostic effectiveness versus adverse effects of vacuum-assisted core
      biopsy (Mammotome). METHODS: 314 NPBLs with a dubious ultrasound and/or
      radiographic appearance were subjected to mammography-guided (86) or ultrasound
      guided (228) Mammotome biopsy. RESULTS: The procedure could be completed and was
      diagnostic in 305 cases (P < 0.0001). Adverse events were transient light
      headedness. In two cases and moderate bleeding in three cases. Histological
      processing of the biopsies showed 227 cases of benign disease (74.42%), 68 cases
      of carcinoma (20 carcinomas in situ and 48 infiltrating carcinomas) (22.29%),
      nine cases of atypical ductal hyperplasia (2.95%) and one atypical lobular
      hyperplasia (0.33%). Only 12 patients reported mild discomfort relative to the
      procedure. The difference between the number of patients reporting discomfort and
      that of patients reporting no discomfort at all was highly significant (P <
      0.0001). CONCLUSIONS: The results confirm that Mammotome biopsy is a highly
      effective procedure for the diagnosis of NPBLs, with minimal negative effects.

PMID- 16277104
TI  - Usefulness of ultrasound-guided fine-needle aspiration cytology in the diagnosis
      of non-palpable small thyroid nodules.
AB  - AIMS AND BACKGROUND: Diverse and contradictory approaches have been suggested for
      the management of non-palpable thyroid nodules. The aim of our study was to
      evaluate the indications and limits of ultrasound-guided fine-needle aspiration
      cytology (US-FNAC) in non-palpable infracentimetric thyroid nodules. METHODS AND
      STUDY DESIGN: From September 2003 to December 2004 we observed 325 patients with
      non-palpable thyroid nodules. We divided our series into three groups according
      to the diameter of the lesion in order to verify the effectiveness of US-FNAC for
      lesions of less than 1 cm. RESULTS: We assessed the cases with satisfactory and
      unsatisfactory results in the three groups into which the sample was divided (4
      mm to 1 cm; 10.1 mm to 15 mm, and 15.1 mm to 25.5 mm). Our statistical analysis
      by means of the z-test showed there was no significant (5%) difference in the
      percentage distribution of the unsatisfactory results in the three groups.
      CONCLUSIONS: Fine-needle cytology appears to be a useful diagnostic tool also for
      nodules of less than one cm because the percentage of unsatisfactory results is
      not related to the size of the nodule.

PMID- 16277105
TI  - Posterior mediastinal hyperfunctioning insular thyroid carcinoma.
AB  - A case is presented of a posterior mediastinal mass arising in a 57-year-old
      woman with severe compressive cervical symptoms and hyperthyroidism. Computed
      tomography showed intrathoracic thyroid tissue that displaced the trachea towards
      the front and the right and invaded the posterior mediastinum. Pathological
      examination showed features of a poorly differentiated (insular) thyroid
      carcinoma. To the best of our knowledge, this is the first reported case of a
      posterior mediastinal insular thyroid carcinoma with thyroid hyperfunction.

PMID- 16277106
TI  - Fatal immunodeficiency in a patient with thymoma and Good's syndrome.
AB  - Thymoma is a rare tumor characterized by an association with autoimmune diseases.
      Immunological abnormalities are increasingly being recognized in thymoma patients
      and are the cause of a peculiar susceptibility to infections. The authors present
      the clinical history of a thymoma patient affected by fatal immunodeficiency.

PMID- 16277107
TI  - Pulmonary valve papillary fibroelastoma. A case report.
AB  - We present a case of pulmonary valve fibroelastoma diagnosed by echocardiogram
      which was confirmed by surgical resection in a patient in whom elective coronary
      artery bypass surgery was performed. The patient had no clinical or
      constitutional symptoms suggesting the presence of an intracardiac tumor. Routine
      preoperative transthoracic echocardiography revealed a pulmonary valve tumor.
      Histopathological analysis resulted in a diagnosis of papillary fibroelastoma.
      Papillary fibroelastomas are rare and benign cardiac tumors. They usually arise
      from the cardiac valves. In the literature we found only a few cases, so it seems
      there is a need for further description of additional cases of pulmonary valve
      fibroelastoma.

PMID- 16277108
TI  - Breast vasculitis presenting as a tumor-like lesion. A case report.
AB  - Breast vasculitis presenting as a tumor-like lesion is rare. The differential
      diagnosis in these cases can be extremely difficult but is very important for
      treatment and follow-up. We report the case of a 80-year-old woman who was
      admitted to our service with a lesion resembling an inflammatory carcinoma of the
      breast. We discuss the pathological and clinical characteristics, the
      presentation, assessment and treatment of this case and its resolution. Few
      reports in the literature have addressed the possible occurrence of systemic
      vasculitis mimicking cancerous lesions. The most common location of such lesions
      was shown to be the breast in one review. Although rare, such manifestations can
      be effectively recognized and treated.

PMID- 16277109
TI  - Coronary artery stenosis following mediastinal radiation therapy. Case report and
      review of the literature.
AB  - A case of coronary artery stenosis following mediastinal radiation therapy in a
      young woman and a review of the literature offer indications on the criteria to
      follow in the diagnosis of coronary artery disease secondary to mediastinal
      radiation therapy.

PMID- 16277110
TI  - Cost of insurance policies for investigator-initiated cancer clinical trials in
      Italy.
AB  - BACKGROUND: Clinical trials with non-profit promoters are frequently performed in
      oncology and represent a highly valuable source of information. METHODS: To
      describe the costs of insurance policies and their determinants, data were
      collected from 12 Italian non-profit promoters of cancer trials. The cost of
      policies was expressed as per-patient premium. RESULTS: Sixty-two quotations
      issued by only two companies were collected, relative to 44 trials proposed for
      quotation between December 1998 and February 2003. Only the date of quotation was
      significantly associated with the cost (P = 0.0003) of quotations by Company A
      for policies with a deductible, with cost increasing over time. Date of quotation
      (P = 0.0002), sample size (P = 0.008) and number of study arms (P = 0.02) were
      independently associated with the cost of no-deductible policies quoted by
      Company A. Only the number of study arms was significantly associated with cost
      (P = 0.0001) in no-deductible policies quoted by Company B. CONCLUSION: There is
      insufficient competition among companies for insurance of cancer trials with non
      profit promoters. Many variables that affect the trial risk profile from a
      clinical perspective are not associated with insurance cost. Date of quotation is
      among the strongest determinants of the cost, which has sharply increased over
      time. This trend may become a serious problem for non-profit promoters of cancer
      clinical trials.

PMID- 16277111
TI  - [Bevacizumab combined with chemotherapy in the treatment of solid tumors: the
      novelty from ASCO 2005].

PMID- 16277112
TI  - [Epoetin alfa in the treatment of secondary anemia induced by chemotherapy].

PMID- 16277113
TI  - [Toward the cure of "early-stage" solid tumors: the role of docetaxel].

PMID- 16277114
TI  - Is fish the foodchain end point for human methylmercury contamination?

PMID- 16277115
TI  - Concentrations of selected persistent organochlorine contaminants in store-bought
      foods from northern Alaska.
AB  - OBJECTIVES: We address marine and terrestrial mammal blubber, liver, muscle,
      kidney, heart, tongue, maktak and maktaaq (epidermis and blubber from bowhead,
      beluga whales, respectively), and fish muscle and livers, as commonly consumed
      tissues in subsistence communities across northern Alaska in the context of
      organochlorine (OC) contamination of store-bought foods. Human exposure to
      contaminants from biota, as part of a subsistence diet, has been superficially
      evaluated in numerous studies (focused on liver and blubber), but are limited in
      the type of tissues analyzed, and rarely consider the contaminants in the
      alternatives (i.e., store-bought foods). STUDY DESIGN: Concentrations from
      published literature on selected persistent organochlorine contaminants (OCs) in
      eight tissues of the bowhead whale and other biota (1) were compared to store
      bought foods evaluated in this study. RESULTS: As expected, store-bought foods
      had lower concentrations of OCs than some tissues of the marine mammals
      (especially blubber, maktak, and maktaaq). However, blubber is rarely eaten alone
      and should not be used to give consumption advice unless considered as a portion
      of the food item (i.e., maktak). This study indicates that the store-bought food
      alternatives have detectable OC concentrations (e.g., < 0.01 to 22.5 ng/g w.w.
      for hexachlorobenzene) and, in many cases, have greater OC concentrations than
      some subsistence food items. Many wildlife tissues had OC concentrations similar
      to those quantified in local store-bought food. CONCLUSIONS: Switching from the
      traditional diet to western store-bought foods will not always reduce exposure to
      OCs. However, raw blubber-based products are clearly more contaminated with OCs
      due to lipid content. A detailed profile of traditional/country foods and western
      foods consumed by subsistence communities of northern Alaska is required to
      address chronic exposure in more detail for the diverse sources of foods
      (subsistence use and commercially available) and the widely varying
      concentrations of contaminants reported therein. This should be combined with
      biomonitoring people dependent upon subsistence foods. Further assessment of
      essential and non-essential elements, emerging contaminants (e.g. brominated
      flame retardants), etc. should be conducted in order to improve our understanding
      of the differences and similarities between wildlife and store-bought foods.

PMID- 16277116
TI  - Lead content in autopsy liver tissue in samples from Greenlandic Inuit and Danes.
AB  - OBJECTIVES: To measure the quantity of lead (Pb) in liver tissue samples from
      Greenlandic Inuit, and compare the results with those obtained in Caucasian
      Danes. STUDY DESIGN: Observational, descriptive survey on environmental
      pathology. METHODS: The setting was related to forensic medicine and hospitalised
      care in Nuuk, Ilulissat and Copenhagen. Participants were 50 Greenlandic Inuit
      (27 men) with a median age of 61 years (range 23-83) and 74 Danes (44 men) with a
      median age of 60 years (range 15-87). Liver tissue samples (normal by macroscopic
      and microscopic examination) were obtained at autopsy. Total liver lead content
      was measured by X-ray fluorescence spectrometry with a detection limit of 0.05
      micromol/kg dry weight. RESULTS: In the entire series, Inuit had higher liver
      lead contents than Danes (p < 0.0001). Inuit men had higher liver lead content
      than Inuit women (p = 0.02). In Danes, men tended to have higher liver lead
      contents than women, but the difference was insignificant. The median (5-95
      percentile) lead content was 14.96 micromol/kg dry liver (4.83-74.80) in Inuit,
      and < 0.05 micromol/kg dry liver (< 0.05-29.44) in Danes. All Inuit had liver
      lead contents above the detection limit, whereas 60 Danes (81%) had liver lead
      content below the detection limit. There was a positive correlation between liver
      lead content and age in both Inuit (rs = 0.46, p = 0.002) and Danes (n = 14; rs =
      0.71, p = 0.01). Inuit had higher hepatic lead indices (liver lead content
      divided by age) than Danes (p < 0.0001). In Inuit, median hepatic lead index was
      0.258, being higher in men than in women (p = 0.02). In Danes, the median hepatic
      lead index was 0.001, again higher in men than in women (p = 0.03). CONCLUSIONS:
      Our results show a gender-related difference in hepatic lead content, i.e. Inuit
      men have higher liver lead contents than women. Furthermore, Inuit men and women
      have higher hepatic lead contents than Danish men and women. In both Inuit and
      Danes, the liver lead content increases with age. One reason for the high lead
      levels in Inuit may be ingestion of seabirds contaminated by lead shot.

PMID- 16277117
TI  - Polychlorinated biphenyls in serum of the Siberian Yupik people from St. Lawrence
      Island, Alaska.
AB  - OBJECTIVES: To determine serum levels of polychlorinated biphenyls (PCBs) in
      Siberian Yupik adults from St. Lawrence Island, Alaska, and to determine the
      relative contribution of atmospheric transport of PCBs and local contamination to
      body burdens. STUDY DESIGN: Siberian Yupiks of various ages were recruited from
      three populations: residents of the village of Gambell, residents of the village
      of Savoonga who did not have family hunting camps near the Northeast Cape (NEC),
      a Formerly Used Defense Site (FUDS) known to be contaminated with PCBs, and
      residents of Savoonga whose families had a hunting camp at the NEC. METHODS:
      Levels of PCBs were measured in serum samples from 130 people, ages 19-76. These
      Alaska Natives follow a traditional diet high in marine mammals and fish, which
      bioconcentrate organochlorine compounds that migrate to the Arctic via global air
      transport and ocean currents. RESULTS: The lipid-adjusted serum PCB levels of
      those members of families with hunting camps at the NEC had a mean lipid-adjusted
      PCB concentration of 1,143 ppb, whereas other residents of Savoonga had values of
      847 ppb and residents of Gambell had values of 785 ppb. CONCLUSIONS: Our
      observations suggest that atmospheric transport of PCBs contributes to levels in
      the Yupik people, but that the abandoned military site at the NEC may also
      contribute to the human body burden in those individuals who have either spent
      substantial time or consumed food from there.

PMID- 16277118
TI  - Towards a better understanding of First Nations communities and drinking and
      driving.
AB  - OBJECTIVES: First Nations young people are over-represented in fatal alcohol
      related crashes, necessitating culturally sensitive data that sheds light on this
      major health issue. The objective of this study was to understand why young First
      Nations drivers, aged 18 to 29 years old, become involved in drinking and driving
      as normal behavior displayed through socio-cultural patterns. STUDY DESIGN AND
      METHODS: Sixty-five First Nations respondents were individually interviewed in
      nine Alberta locations. Semi-structured interviews, focusing on socio-cultural
      patterns, norms and community ethos affecting alcohol consumption, drinking and
      driving, and drinking and driving interventions, were used. RESULTS: Community
      norms play a significant role in the drinking and driving behaviors of First
      Nations people. First Nations communities experience reckless driving, neighbors
      with alcohol and drug abuse problems, violence, economic disparity, boredom and
      racism, all of which contribute to responses of alcohol abuse and drinking and
      driving. Both are considered to be normal, community-endorsed behaviors,
      reflecting situational needs and ready-at-hand usage. Furthermore, the grid of
      rural roadways is an important contributor to drinking and driving and a
      community sense of practical living. Also of importance was the finding that
      young people embraced their parents' alcohol-related problem behaviors on the
      basis that "what is okay for the parents is okay for me." Finally, First Nations
      young people believe in personally stopping a drunken person from driving, but
      the risk of community censure, social discomfort and risk of physical and verbal
      abuse mitigate against them taking action. CONCLUSIONS: Living in First Nations
      communities is socially complex, highly emotionally charged, and peer-pressured.
      Drinking and driving and alcohol abuse amongst First Nations people reflect the
      community social structure, daily pressures and norms of behavior. Hence, to
      reduce drinking and driving casualties amongst First Nations young people,
      intervention strategies must address systemic issues, namely local people's
      social realities, norms, as well as local and peer relationships.

PMID- 16277119
TI  - Focal aspects of co-operation between the private, public and third sectors in a
      sparsely populated area in northern Finland.
AB  - OBJECTIVES: The purpose of this study was to describe and analyze the focal
      aspects of co-operation between the private, public and third sectors in a
      sparsely populated area of northern Finland. The study is part of a larger
      research and development project, which produced a model of co-operation between
      the sectors in a sparsely populated area of northern Finland. STUDY DESIGN: The
      study was qualitative. An expert group (n = 12), consisting of representatives
      from the private (n = 4), public (n = 4) and third sectors (n = 4), was
      recruited. METHODS: The data were collected using the focus groups method. The
      focus group method was feasible here because the development of co-operation
      between the different sectors was new, and the aim was to find novel operating
      models. RESULTS: The focal aspects of co-operation between the different sectors
      consisted of the objectives of operation, the client's perspective, the
      structures, the contents of operation and the operating culture. CONCLUSIONS: An
      expert group of representatives from the different sectors was a functional
      starting-point for the development of co-operation. The group also made it
      possible to reach representatives of the sectors more widely by means of the
      questionnaire survey. The operation of the expert group clearly involved elements
      of network management, because the group aimed to take into account the interests
      of all network actors. Network management at this stage of the project can be
      considered successful. To maintain co-operation at the concrete level, shared
      self-guided activities between the sectors will be needed.

PMID- 16277120
TI  - Diabetes among Inuit migrants in Denmark.
AB  - OBJECTIVES: The study aimed to estimate the prevalence of diabetes and impaired
      glucose intolerance (IGT) among Inuit migrants living in Denmark, and to compare
      with findings from Greenland. Further, we analyzed determinants for diabetes and
      impaired glucose metabolism. STUDY DESIGN: Cross-sectional, population-based
      epidemiological study. METHODS: This cross-sectional study included randomly
      selected Inuit migrants in Denmark aged 34 years and above. Diabetes and IGT were
      diagnosed using the oral glucose tolerance test. Body mass index (BMI) and waist
      circumference were measured, and blood samples were taken from each subject.
      Socio-demographic characteristics were investigated using a questionnaire. For
      comparison, data from the Greenland Population Study were used (n = 917).
      RESULTS: Of 506 eligible subjects, 256 (51%) participated. Twenty-six subjects
      had diabetes (10.2%) and twenty-eight had IGT (10.9%). Of those with diabetes,
      64% had not been previously diagnosed. The prevalences of diabetes and IGT were
      not significantly different from those among Inuit in Greenland. Significant
      predictors of diabetes and impaired glucose metabolism (IGM) were found to be
      age, waist circumference and physical inactivity. The association between waist
      circumference and diabetes was significantly stronger among Inuit migrants in
      Denmark than among Inuit in Greenland. CONCLUSIONS: The prevalence of diabetes is
      high among the Inuit migrants in Denmark. However, unlike that reported in most
      studies, the prevalence was not significantly higher in the migrant population
      compared with the population of origin.

PMID- 16277121
TI  - Cardiovascular disease and risk factors in three Alaskan Eskimo populations: the
      Alaska-Siberia project.
AB  - OBJECTIVES: To determine the prevalence of CVD and to identify and characterize
      associated risk factors in three distinct Eskimo populations. STUDY DESIGN: Cross
      sectional. METHODS: A slightly modified Strong Heart Study protocol was followed
      to examine 454 participants, aged 25-91, from four villages. RESULTS: Overall, 6%
      of the participants under 55 years of age and 26% of those > or = 55 years of age
      showed evidence of CHD by ECG, or in patient records. The prevalence of "definite
      coronary heart disease" (CHD) in women with glucose intolerance (GI) was 21.0%,
      compared to 2.4% in those with normal glucose tolerance (NGT). Men had comparable
      values of 26.7% and 6.3%. In addition, comparable values for "possible CHD" were
      29.7% vs 6.0% for women and 21.4% vs 8.0% for men. GI was associated with
      relatively higher prevalences of CHD in women than in men (prevalence ratio = 8.5
      vs 4.3). CHD was significantly related to age, glucose intolerance and insulin.
      Hypertension and obesity were significantly associated with CHD only in some
      ethnic groups. The prevalence of current smokers was 56%. CONCLUSIONS: Recent
      changes in lifestyle and diet of Alaskan Eskimos, leading to obesity,
      hypertension, insulin resistance and DM, contribute to an increased risk for
      cardiovascular disease.

PMID- 16277122
TI  - Eskimos have CHD despite high consumption of omega-3 fatty acids: the Alaska
      Siberia project.
AB  - OBJECTIVES: The thirty-year-old hypothesis that omega-3 fatty acid (FA) may
      "reduce the development of thrombosis and atherosclerosis in the Western World"
      still needs to be tested. Dyerberg-Bang based their supposition on casual
      observations that coronary atherosclerosis in Greenlandic Inuit was 'almost
      unknown' and that they consumed large amounts of omega-3 FAs. However, no
      association was demonstrated with data. STUDY DESIGN: Cross-sectional study.
      METHODS: 454 Alaskan Eskimos were screened for coronary heart disease (CHD),
      using a protocol that included ECG, medical history, Rose questionnaire, blood
      chemistries, including plasma FA concentrations, and a 24-hour recall and a food
      frequency questionnaire assessment of omega-3 FA consumption. RESULTS: CHD was
      found in 6% of the cohort under 55 years of age and in 26% of those > or = 55
      years of age. Eskimos with CHD consume as much omega-3 FAs as those without CHD,
      and the plasma concentrations confirm that dietary assessment. CONCLUSIONS:
      Average daily consumption of omega-3 FAs among Eskimos was high, with about 3-4
      g/d reported, compared with 1-2 g/d used in intervention studies and the average
      consumption of 0.2 g/d by the American population. There was no association
      between current omega-3 FA consumption/blood concentrations and the presence of
      CHD.

PMID- 16277123
TI  - Omega-3 fatty acids improve glucose tolerance and components of the metabolic
      syndrome in Alaskan Eskimos: the Alaska Siberia project.
AB  - OBJECTIVES: To test the hypothesis that the unusually low prevalences of insulin
      resistance (IR), metabolic syndrome (MS) and diabetes (DM) in Alaskan Eskimos,
      compared to American Indians, is related to the traditional Eskimo diet, high in
      C20-C22 omega-3 fatty acids (FAs). To determine if the relatively low blood
      pressures, low serum triglycerides and high HDL cholesterol levels in Eskimos
      result from high omega-3 FA consumption. STUDY DESIGN: Cross-sectional study.
      METHODS: We measured plasma FA concentrations in 447 Norton Sound Eskimos (35-74
      years of age) and screened for DM, CHD and associated risk factors. A dietary
      assessment (24-hr recall) was obtained for comparison the day before the blood
      sampling. RESULTS: Plasma omega-3 FA concentrations were highly correlated with
      dietary omega-3 FAs and HDL levels and inversely correlated with plasma levels of
      insulin, 2-h insulin (OGTT), HOMI-IR, 2-h glucose (OGTT), triglyceride levels and
      diastolic blood pressure. CONCLUSIONS: High consumption of omega-3 FAs positively
      affects components of the MS, insulin sensitivity and glucose tolerance. This
      finding suggests that high consumption of C20-C22 omega-3 FAs protects against
      the development of the MS and glucose intolerance.

PMID- 16277124
TI  - A successful diabetes prevention study in Eskimos: the Alaska Siberia project.
AB  - OBJECTIVES: To test the efficacy of a simple intervention method to reduce risk
      factors for type 2 diabetes (DM) and cardiovascular disease (CVD) in Alaskan
      Eskimos. STUDY DESIGN: The study consisted of 1) a comprehensive screening for
      risk factors of 454 individuals in 4 villages, 2) a 4-year intervention and 3) a
      repetition of the screening in year 5 to test the efficacy of the intervention.
      METHODS: Personal counseling (1hr/year) stressed the consumption of more
      traditional foods high in omega-3 fatty acids and less of certain specific store
      bought foods high in palmitic acid, which was identified as being associated with
      glucose intolerance. RESULTS: The intervention resulted in significant reductions
      in plasma concentrations of total cholesterol (p = 0.0001), LDL cholesterol (p =
      0.0001), fasting glucose (p = 0.0001), diastolic blood pressure (p = 0.0007) and
      improved glucose tolerance (p = 0.0006). This occurred without loss of body
      weight. Sixty percent of the participants had improved glucose tolerance; only
      one of the 44 originally identified with impaired glucose tolerance (IGT)
      developed DM during the study. CONCLUSIONS: Dramatic improvements of risk factors
      for DM and CVD were achieved in the intervention by primarily stressing the need
      for changes in the consumption of specific fats. The results suggest that fat
      consumption is an important risk factor for DM.

PMID- 16277125
TI  - [Relapsing infections with Clostridium difficile].
AB  - Two women, aged 78 and 85 years, presented with watery diarrhoea and fever after
      a course of antibiotic therapy. Pseudo-membranous colitis was diagnosed, which
      was adequately treated. In both patients the C. difficile colitis relapsed, which
      was successfully treated with a pulse and tapering scheme of vancomycin. C.
      difficile infection is a frequent cause of antibiotic-associated diarrhoea.
      Clinical presentation can vary in severity. Cytotoxin testing, immunoassay and
      endoscopy are important tools in diagnosing C. difficile colitis. Like the first
      infection, the first relapse must be treated with metronidazole or vancomycin. To
      treat a second relapse, a pulse and tapering dose of vancomycin has been
      recommended. Nevertheless, multiple recurrences may occur, which are difficult to
      treat.

PMID- 16277126
TI  - [Social medical guidance to achieve resumption of work: an outdated concept].
AB  - In the Netherlands there is a strict separation between the attending physician,
      i.e. the general practitioner, and the occupational physician. However, they are
      supposed to cooperate so that sick-listed patients will return to work earlier.
      It has now been demonstrated that this cooperation is far from sufficient and
      that all the expended effort has not led to an increase in patient satisfaction.
      It has to be admitted that the cooperation has failed. There is a strong need for
      adherence to guidelines, for quality audits and for scientific investigation in
      this sector.

PMID- 16277127
TI  - [Statins for the prevention of colorectal carcinoma: not yet recommended].
AB  - Statins are widely prescribed as lipid-lowering agents in the primary and
      secondary prevention of cardiovascular disease. They are increasingly associated
      with potential chemopreventive effects with respect to cancer. A recent case
      control study reported a 47% relative reduction in the risk of colorectal cancer
      associated with statin use after adjustment for other known risk factors. There
      is evidence of an inhibitory effect of statins on colorectal carcinogenesis from
      in vitro studies, animal experiments, and observational and epidemiological
      reports in humans. Although statins seem promising as chemopreventive agents, it
      is still too early to recommend their use against colorectal cancer outside the
      context of clinical trials.

PMID- 16277128
TI  - [Perforator flaps--the evolution of a reconstructive surgical technique].
AB  - Trauma, oncological resections and pressure sores can cause major soft tissue
      defects. The evolution of cutaneous, myocutaneous, and fasciocutaneous flaps
      currently makes possible the restoration of contour and, in many cases, function.
      This evolution was closely related to the increased understanding of the vascular
      anatomy of the skin and subcutis and has led to the development of perforator
      flaps. A perforator flap is a large flap of skin that survives on a single
      vascular stalk that perforates the muscle, referred to in briefas a 'perforator'.
      This has its origin in a larger vascular stalk that runs beneath the muscle. The
      vascular stalk of such a perforator flap can be lengthened by dissecting the
      perforator from the muscle in continuity with the vessels running beneath the
      muscle. Moreover, the larger diameter of these vessels facilitates the creation
      of a vascular anastomosis in the receptor area. By the use of such perforator
      flaps, proper innervation and a good blood supply to the flap can be combined
      with less morbidity at the donor site. Important possibilities include the
      filling of a dorsal (decubitus) defect and breast reconstruction.

PMID- 16277129
TI  - [Revised guideline "Antiretroviral Treatment"].
AB  - In the revised guideline 'Antiretroviral treatment' produced by the Dutch Society
      of Aids-Treating Physicians and the Dutch Institute for Healthcare Improvement
      (CBO), the following major changes have been made to the 2000 guideline.
      Treatment of adult HIV-infected patients should start when the number of CD4
      cells remains consistent at >200 cells x 10(6)/l. Antiretroviral therapy is
      recommended when CD4-cell levels are 200-350 cells x 10(6)/l and HIV-RNA load is
      higher than 100,000 copies/ml. In therapy-naive adults combinations of 2
      nucleoside reverse transcriptase inhibitors (NRTIs) plus 1 non-nucleoside reverse
      transcriptase inhibitor (NNRTI) and combinations of 2 NRTIs plus 1 protease
      inhibitor are equally effective; NNRTIs are preferable to protease inhibitors due
      to their relatively easy dosage regimen. In order to optimize individual dosage
      regimens, plasma drug levels should be measured at 4 and 24 weeks after the start
      of treatment in therapy-naive patients. Patients with pre-existing disturbances
      of lipid metabolism or familial hypercholesterolaemia should not receive protease
      inhibitors as therapy of first choice. Genotyping is indicated in virological
      failure and before the start of initial therapy in patients infected in Europe
      and the United States of America. In order to prevent HIV transmission from
      mother to child, all pregnant HIV-infected women (also if their HIV-RNA load is
      undetectable) should receive HIV treatment starting in the 24th week of
      gestation. Children of HIV-seropositive mothers should be treated with
      antiretrovirals for 4 weeks after birth. In co-infected patients, the choice of
      anti-hepatitis B drugs should be determined by whether or not there is also an
      indication for HIV treatment. Treatment for tuberculosis should preferably be
      initiated 1-2 months prior to the start of HIV treatment in co-infected patients.
      Following an occupational needlestick accident or unprotected-sex event, post
      exposure prophylaxis should be offered due to the increased risk of HIV
      transmission.

PMID- 16277130
TI  - [Diagnosis image (250). A tachypnoeic neonate with rightsided prominence of heart
      sounds].
AB  - In a male neonate pneumonia and situs inversus were diagnosed: Kartagener's
      syndrome (primary ciliary dyskinesia).

PMID- 16277131
TI  - [Limited change in the quality of the social medical guidance and in the
      satisfaction of sick-listed patients, after collaborative projects between
      general practitioners and occupational physicians].
AB  - OBJECTIVE: To evaluate whether regional projects for collaboration between
      general practitioners (GPs) and occupational physicians (OPs) improved the
      quality of their social medical guidance (SMG) and the satisfaction of their
      patients. DESIGN: Evaluation study with before and after measurements with
      respect to the same GPs and OPs. METHOD: Structured interviews were conducted
      with 58 GPs and 83 OPs regarding the SMG of their sick-listed patients. Before
      the project, the SMG of 1109 sick-listed patients was assessed and after the
      project, 1 or 1.5 years later, the SMG of 1121 sick-listed patients. These
      patients were sent a questionnaire by means of which their satisfaction could be
      assessed. RESULTS: After the projects, the quality ofthe diagnosis by the OPs was
      improved and they also more often adhered to the official guidelines of the KNMG
      (Royal Netherlands Medical Association) when contacting the GP about a patient.
      The GPs more often contacted the OP if they needed more information about a
      patient after reaching a diagnosis. Nevertheless, in half to three-quarters of
      the patients for whom contact between GPs and OPs was indicated, this contact did
      not take place. There was no significant increase in patient satisfaction. Before
      the projects, patients gave their GP a grade of 8.2 on a 10-point scale and after
      the projects this was 8.5; the OPs were given a grade of 7.5 both times. Further
      analysis showed that there was no significant relation between the quality ofthe
      SMG and the patient's satisfaction with the doctor. CONCLUSION: Although there
      was some improvement in the quality of the SMG, there was still insufficient
      cooperation between GPs and OPs compared to the guidelines. An increase in
      patient satisfaction was not demonstrated.

PMID- 16277132
TI  - [Acute occlusion of the renal artery treated by means of rheolytic thrombectomy].
AB  - A 64-year-old woman presented with recurrent infarction of the right kidney.
      Because of suspected dysfunction of the contralateral kidney, revascularisation
      of the occluded right renal artery was attempted. Local thrombolysis with
      urokinase was unrewarding. So-called rheolytic thrombectomy by means of a
      Hydrolyser was successful in opening the right main renal artery. Although
      recovery of right renal function was not complete, renal scintigraphy confirmed
      salvage of most of the right kidney parenchyma.

PMID- 16277133
TI  - [Progressive ataxia and cognitive deficits caused by premutation in the fragile-X
      mental retardation gene].
AB  - A 75-year-old man had progressive difficulty with walking, intention tremor,
      ataxia, and mild cognitive deficits. MRI scan ofthe brain showed symmetrical
      hyperintensities in the middle cerebellar peduncles. DNA analysis ofthe fragile-X
      gene revealed an expansion of 150-200 repetitions in the FMR1-gene, compatible
      with a premutation in the fragile-X gene. Two years later, after progression of
      the symptoms, the patient was admitted to a nursing home. The clinical picture of
      intention tremor, parkinsonism and ataxia with white matter lesions and atrophy
      on MRI occurs in carriers of this premutation and has recently been described as
      the fragile-X-associated tremor/ataxia syndrome. Recognition of this clinical
      picture is important for the patient but also for the relatives, since female
      carriers of the premutation have an increased risk of offspring with the fragile
      X syndrome.

PMID- 16277134
TI  - [An unusual cause of meningo-encephalitis: Japanese encephalitis].
AB  - Two women, 29 and 30 years of age, who had visited Indonesia and Thailand,
      respectively, during the summer, presented with diarrhoea, headache, fever and
      later neurological symptoms. The first patient had to be sedated because of
      restlessness and was admitted to the intensive-care unit for intravenous
      antimicrobial therapy; the second became comatose and received intravenous
      rehydration and antipyretics. No diagnosis was made during the acute phase ofthe
      illness, but later there was serological evidence of Japanese encephalitis. Both
      patients recovered, but memory and concentration difficulties persisted for a
      long time. Due to the increase in travelling, we see more and more cases of
      (rare) imported diseases. Japanese encephalitis is a viral infection that causes
      50,000 cases each year in Asia with a mortality of 30%. The risk of transmission
      for tourists is very low. Most infections with Japanese encephalitis virus do not
      lead to symptomatic disease; only 0.1-5% of infections lead to clinical disease.
      The symptoms are initially non-specific, consisting of general discomfort and
      diarrhoea. After this, patients can develop headache, decreased consciousness and
      sometimes convulsions. Therapy consists of supportive care. For travellers at
      high risk of exposure, a formalin-inactivated vaccine is available. For the
      proper diagnosis of rare imported diseases, it is advisable to consult an
      infectious-disease specialist or microbiologist at an early stage when evaluating
      a patient who has recently returned from the tropics.

PMID- 16277135
TI  - [Diagnostic methods for Helicobacter pylori infection in children].

PMID- 16277136
TI  - Romantic relationships for women with anorexia nervosa: an integrative literature
      review.
AB  - OBJECTIVE: To critically appraise literature concerning romantic relationships
      for women with anorexia nervosa (AN), and to gain perspective on future research
      directives. METHOD: Key electronic databases, reference lists, and journals were
      searched. The search was limited to features of romantic relationships and their
      quality. Nineteen studies were critiqued and abstracted. RESULTS: All 19 studies
      used a quantitative design; no qualitative studies were retrieved. Methodological
      strengths of these studies included confounder control and appropriate
      statistical analyses for design. Weaknesses included a failure to declare study
      designs, address sources of bias, and justify study samples, as well as a lack of
      con-founder control. DISCUSSION: The review drew attention to the varied
      relational experiences and marked relationship dissatisfaction expressed by women
      with AN. However, an understanding of relationship quality and its dynamic nature
      remains limited. Future research should focus on how meanings are negotiated in
      relationships, providing detailed descriptions of the women's experiences, which
      is best done with qualitative study. Well-conducted longitudinal research should
      address questions that cannot be answered by current research designs, such as
      temporality.

PMID- 16277137
TI  - Binge eating disorder in obesity: comparison of different therapeutic strategies.
AB  - The aim of this study (duration: 12 months) was to compare different integrated
      therapeutic approaches for the therapy of Binge Eating Disorder (BED). A sample
      of 65 female severely obese BED was randomly divided into 3 groups: the first one
      was treated by Cognitive-Behavioural Therapy (CBT) alone; the second one was
      treated by SSRI antidepressant therapy (fluoxetine) alone; the remaining was
      treated by a combination of CBT plus fluoxetine. All groups received group
      nutritional training and individual dietary counselling. The initial fluoxetine
      dose (20 mg/day) was adjusted (up to 60 mg/day) according to frequency of binge
      eating. During the first 4 weeks, all subjects underwent an in-patient dietary
      treatment aimed to achieve at least a 5% weight loss, which was continued during
      the out-patient treatment phase. At the beginning and at the end of the therapy
      the patients were evaluated by the Minnesota Multiphasic Personality - 2 and by
      the Eating Disorder Inventory - 2. The results showed that the two groups which
      underwent psychotherapy resulted in a better outcome - in terms of number of
      bingeing episodes, maintenance of weight loss reduction from baseline and
      psychological well being - than the group treated with pharmacological therapy
      alone. Finally, the study underlines the importance of a multidisciplinary
      approach to the treatment of Binge Eating Disorder.

PMID- 16277138
TI  - Influences of mothers' dieting behaviors on their junior high school daughters.
AB  - We investigated the influences of mothers' dieting behaviors on their junior high
      school daughters. We assessed dieting behaviors and eating habits in 221 pairs of
      mothers and their junior high school daughters using questionnaires. The subjects
      were classified into an extraordinary-diet (Ex-D) group, who attempted to diet
      rapidly with unhealthy methods, a structured-diet (St-D) group, who attempted to
      diet gradually with healthy methods, and a non-diet (N-D) group, using the
      questionnaire scores. 1) A significant correlation was observed in the
      distribution of dieting behavior groups between the mothers and their daughters.
      2) The scores for dieting behavior of the mothers whose daughters were classified
      into the Ex-D group were significantly higher in several question items compared
      with those of the mothers whose daughters were classified into the N-D group. 3)
      The scores for eating consciousness of the mothers whose daughters were
      classified into the Ex-D group were significantly lower for the item "Cooking is
      a fun pastime" compared with those of the mothers whose daughters were classified
      into the St-D or N-D groups. 4) The number of experiences of conversation with
      daughters about diet for the mothers whose daughters were in the Ex-D group was
      significantly higher than that for the mothers whose daughters were classified
      into the N-D group. The mothers' dieting behavior, eating consciousness, and
      number of conversations with daughters about diet influenced dieting behaviors in
      their junior high school daughters. Appropriate education of mothers would be
      useful to prevent their daughters' inappropriate diet.

PMID- 16277139
TI  - Gender differences in the progression of co-morbid psychopathology symptoms of
      eating disordered patients.
AB  - This study examined the utility of the Personality Assessment Inventory (PAI) in
      screening for comorbid psychopathology in eating disordered males and females
      undergoing residential treatment. The PAI, a self-administered screening tool
      containing 344 items to provide information on 11 clinical constructs, was
      administered at admission and discharge to 181 patients, 154 females and 27
      males. Average age was 26.88 years (SD=9.35) and average length of stay was 58.31
      days (SD=39.94). The results showed that both male and female patients exhibit
      several comorbid disorders at admission to residential treatment and the severity
      of these symptoms was statistically significantly reduced over the course of
      treatment. When comparing differences among genders, the results show that
      females present with more psychopathology symptoms at the start of treatment but
      make better progress than males in reducing these symptoms over time. When
      comparing patients across eating disorder diagnoses, subjects with bulimia
      displayed more severe comorbid symptomatology as compared to those with anorexia
      or other eating disorders. A thorough clinical assessment of eating disordered
      patients including comorbid psychopathology disorders is relevant for clinical
      diagnosis, treatment planning, and perhaps ultimately the outcome of treatment.

PMID- 16277140
TI  - An attempt at distinguishing subgroups of women with anorexia nervosa and bulimia
      nervosa by means of the Defense Mechanism Technique modified (DMTm) and the
      Eating Disorder Inventory (EDI).
AB  - In an attempt to identify diagnostically meaningful subgroups in a group of sixty
      women 18-34 years of age, 19 of them having a DSM-IV diagnosis of anorexia
      nervosa and 41 of bulimia nervosa, a hierarchical cluster analysis was performed
      on their data obtained from the Defense Mechanism Technique modified (DMTm) and
      the Eating Disorder Inventory (EDI). Variables also taken into account in the
      cluster analysis were those of the main diagnosis, depression, personality
      disorder, binge eating, purging, Body Mass Index (BMI), and exercise. Five
      distinct clusters were found. Six of the eight EDI variables and fourteen of the
      twenty DMTm variables were represented in the description of the clusters. One
      anorexic and one bulimic cluster included DMTm signs previously found in patients
      with fibromyalgia. Two bulimic clusters included DMTm signs previously observed
      in patients with either distal or total ulcerative colitis. Hysteria was linked
      with the remaining anorexic cluster. On both EDI and DMTm the two main groups of
      anorexic and bulimic patients displayed few differences. It was mainly the
      various constellations of DMTm variables, interpreted in terms of the Andersson
      developmental and psychodynamic model of the mind, that were crucial for
      understanding the five clusters obtained.

PMID- 16277141
TI  - Beliefs and expectations regarding etiology, treatment and outcome in bulimia
      nervosa.
AB  - OBJECTIVE: To examine pretreatment client beliefs and expectations about the
      causes of bulimia nervosa (BN), and helpfulness of treatment. The association
      between outcome expectations, pretreatment characteristics, and treatment outcome
      was also tested. METHOD: 76 BN clients completed a questionnaire assessing
      beliefs and expectations before participating in a randomized treatment trial.
      RESULTS: Clients attributed their BN to problems of dysphoria, low self-esteem,
      perfectionism, and weight preoccupation. They also anticipated a wide array of
      therapeutic modalities to be helpful, and expected to make changes within 7 weeks
      of treatment. Surprisingly, outcome expectations were not related to treatment
      response. Clients who were identified as treatment optimists were more likely to
      be older, have a longer duration of illness, and greater pretreatment depression
      and BN symptomatology. DISCUSSION: These results are discussed in the context of
      the transtheoretical model, suggesting that veteran BN clients who experience
      greater complications are less ambivalent and more hopeful about change.

PMID- 16277142
TI  - Efficacy of an internet-based behavioral weight loss program for overweight
      adolescent African-American girls.
AB  - OBJECTIVE: This randomized controlled trial tested the efficacy of an internet
      based lifestyle behavior modification program for weight management in African
      American girls. DESIGN: African-American girls were randomly assigned to an
      interactive behavioral internet program or an internet health education program,
      the control condition. The behavioral intervention included internet counseling
      and was highly interactive. The control intervention was a passive (non
      interactive) educational program. Parents were also participants in the study.
      Participants in both treatment groups met in face-to-face sessions on four
      occasions over the first 12 weeks of a 6-month intervention. SUBJECTS: The study
      enrolled 57 African-American adolescent girls (ages 11 to 15 years) who were
      overweight or obese and had at least one biological parent who was obese [body
      mass index (BMI) >30 kg/m2]. Of the 57 participants, 50 (88%) completed the 6
      month trial. MEASUREMENTS: Outcome data, including BMI, body weight, body
      composition, dietary intake, and weight loss behaviors were collected at baseline
      and 6-months later. A computer server tracked utilization of the websites.
      Participation in the program was measured by number of "hits" on the website.
      RESULTS: Compared to the control condition, adolescents in the behavioral
      treatment lost more body fat (group difference =1.6% body fat) and parents lost
      significantly more body weight (group difference =2.1 kg). Utilization of the
      behavioral website by adolescents and parents was associated with positive
      outcome. Dietary fat intake was lowered for adolescents and parents in the
      behavioral treatment group. CONCLUSION: An internet-based behavioral intervention
      was superior to internet-based health education and yielded decreased body fat
      for adolescent girls and decreased body weight for parents.

PMID- 16277144
TI  - [Thumb reconstruction in emergency, not including replantation].
AB  - Many articles have discussed secondary thumb reconstruction but only few have
      been devoted to acute reconstruction. We propose to artificially separate four
      circumstances: (i) the thumb is preservable without associated trauma of the
      fingers. The rule is not to burn the bridge of secondary reconstruction; (ii) the
      thumb is preservable but a neighboring finger is seriously injured and
      functionally condemned. The finger has to be used as a "bank" to borrow the
      necessary anatomical structures for reconstruction of the thumb; (iii) the thumb
      is not preservable and the lesions of a neighboring finger allow to use it for a
      pollicization. The difficult decision is between the immediate transposition or
      maintenance for secondary pollicization. Only finger devascularization is a clear
      indication for acute pollicization; (iv) Finally when the thumb is not
      preservable and there is no associate finger injury, it is difficult to assess
      and inform sufficiently the patient to take a decision. Secondary thumb
      reconstruction is the best choice.

PMID- 16277143
TI  - Management and treatment of eating disorders in an Italian region.
AB  - OBJECTIVE: Eating disorders (ED) are an outstanding health problem in western
      countries, and bear significant mortality, e.g. anorexia nervosa (AN), and
      morbidity. The Liguria Region Health Department set up a study with the support
      of a number of specialists to investigate the number and characteristics of
      patients referred to institutions, how patients were managed, and the healthcare
      facilities and personnel involved. METHODS: The retrospective study required that
      all regional institutions, except two, involved in the treatment of ED during the
      year 2001 filled out a special questionnaire. RESULTS: Twenty-one institutions
      (n=19 public, n=2 private) followed 1,220 patients with ED in the mentioned year.
      The prevalence of such disorders was 6 fold higher in females (1,054 F, 166 M;
      age range 12-32 years). Bulimia nervosa (BN) proved to be the disorder category
      most frequently observed (prevalence 59%) followed by AN (26%, p<0.0001) and ED
      not otherwise specified (EDNOS) (15%, p<0.0001). Most (approximately 90%) of
      these patients were managed in outpatient settings, and a multidisciplinary team
      approach was used in fewer than 20% of cases. Hospitalization (complete or
      partial) was required in 10.5% of patients: 7.1% for mental disturbances and 3.4%
      for severe malnutrition/electrolyte abnormalities. Fewer than one fourth of
      patients was admitted to two specialty units (one public and one private) for
      inpatients in our region with ED. Treatment provided in these centers included a
      specific nutritional rehabilitation program and psychologic/psychiatric care.
      Patients more severely underweight underwent nasogastric or parenteral feeding
      whenever deemed clinically appropriate. The grade of knowledge of ED by general
      practitioners/pediatricians and their links with trained centers were poor.
      CONCLUSIONS: Although our data were obtained from a selected population, thus
      preventing epidemiological conclusions, they show that ED are a significant
      health concern in our region, with BN representing the most common disorder
      diagnosed in the different settings (general or specialized medical practices).
      Overall, the prevalence of such disorders was assessed as six fold higher in
      females than in males. The emerging issues to be improved are: i) poor level of
      communication among different specialists and subsequent scanty use of a
      multidisciplinary team approach in the management of ED ii) insufficient use of
      guidelines for the management of such disorders iii) paucity of specialty
      institutions for inpatients with ED iv) inadequate knowledge of the problem by
      primary care physicians and the community, and poor links with the healthcare
      institutions that might help.

PMID- 16277145
TI  - The ECRL bone-tendon ligamentoplasty for chronic ulnar instability of the
      metacarpophalangeal joint of the thumb.
AB  - We report the results of a new bone-tendon ligamentoplasty for the reconstruction
      of chronic injuries of the ulnar collateral ligament at the metacarpophalangeal
      joint of the thumb. The mean follow-up period was 36 months. Using the Glickel
      grading system, seven patients had excellent results and one patient had good
      results. The mean loss of pinch strength was 10% compared with the contralateral
      thumb. The mean loss of motion at the MP joint was 8%. This technique
      successfully restores the desired long lasting stability while maintaining
      mobility of the thumb's metacarpophalangeal joint.

PMID- 16277146
TI  - Arthrodesis of the trapeziometacarpal joint for basal joint osteoarthritis of the
      thumb: the importance of obtaining osseous union.
AB  - INTRODUCTION: In the surgical treatment of osteoarthritis of the basal joint of
      the thumb, several options are available. The carpometacarpal arthrodesis should
      provide stability, strength and resolution of pain. There is however some
      controversy on the outcome. MATERIALS AND METHODS: In a retrospective study we
      reviewed 34 carpometacarpal joint fusions (26 men, eight women; mean age 48
      years). Two techniques of fixation have been used: staples (16x) and K-wires
      (18x). The follow-up was 5.2 years. RESULTS: The nonunion rate was 39%. Only 60%
      of the patients was satisfied. The DASH score was 32 (standard deviation 18). Key
      pinch force was reduced with 27% of the opposite side. Range of motion was
      slightly reduced: 6 degrees in the interphalangeal joint, 19 degrees in the
      metacarpophalangeal joint. When fusion was obtained patients' satisfaction
      increased to 88%. CONCLUSION: Patient satisfaction was low and nonunion rate was
      high. Better results are obtained in cases with osseous union. More solid
      fixations, perhaps with addition of bone grafts have to be considered.

PMID- 16277147
TI  - [The anterior interosseous flap in wrist and hand surgery: a series of fifteen
      cases].
AB  - INTRODUCTION: Fifteen anterior interosseous flaps were used to reconstruct wrist
      and hand defects in fifteen patients (thirteen men and two women) with a mean of
      38 years (27-42 years). PATIENTS AND METHODS: Seven anterior interosseous
      osteoperiosteal flaps and eight anterior interosseous osteocutaneous flaps were
      used. Seven island flaps and eight free flaps based on the anterior interosseous
      artery were raised. The indications were scaphoid non-union (4 cases), first
      metacarpal non-union (2 cases), proximal phalanx non-union (1 case), Kienbock's
      disease (2 cases), osteocutaneous phalangeal defects (3 cases), osseous capitatum
      defect (1 case) and intracarpal arthrodesis (2 cases). RESULTS: Postoperatively,
      one fracture of the distal end of the radius was noted because of a large
      osteoperiosteal corticotomy. Osseous reconstruction was usually consolidated at
      three months. One failure was noticed (Kienbock's disease). No significant
      deformity was noticed in the donor site. CONCLUSION: The anterior interosseous
      flap seems to be a useful alternative to reconstruct small or moderate defects in
      wrist and hand surgery.

PMID- 16277148
TI  - Intraoperative Bier's block as supplement to insufficient axillary block
      anesthesia in upper extremity surgery.
AB  - The authors reviewed 52 patients who underwent Bier's block, as supplementary
      anesthesia for insufficient axillary block in upper extremity surgical
      procedures. Prior to proceeding to the Bier's block, the mean value of pain using
      the visual optical analogue scale (VAS) was 7.0. In 48 of the patients
      supplementation with the Bier's block was sufficient (mean VAS score of 1.0) and
      all patients were comfortable throughout the procedure. In the remaining four
      patients supplementation with narcotics and sedatives via the other i.v. line was
      required. Intraoperative Bier's block provides a safe and effective alternative
      way of successfully compensating for an insufficient axillary block in upper
      extremity surgical procedures.

PMID- 16277150
TI  - Atraumatic avascular necrosis of an index sesamoid.
AB  - Avascular necrosis of an index sesamoid is our topic. In literature we found a
      lot of papers published about Hallux and the thumb sesamoid. There were only few
      articles concerning index sesamoid pathology. But in contrast to these, there's
      no evidence for trauma, nor arthritis in the personal history of the case
      discussed. This pathology is rare. Diagnosis is difficult. Treatment by sesamoid
      resection was successful.

PMID- 16277149
TI  - [Skin graft and cross finger flap for salvage reconstruction of ring finger
      avulsion].
AB  - An exceptional case of complete cutaneous ring finger avulsion is reported. The
      distal fragment was not replantable because of lack of vessels. The
      reconstruction restored a functional finger.

PMID- 16277151
TI  - [Pathological fragmentation of the sesamoid bone of the index due to repetitive
      micro trauma: a case report and review of the literature].
AB  - Pathology of the sesamoid bones have been rarely described in the literature
      especially those of the index. We present the case of a 45 years old amateur
      tennis player who presented with pain on the radial border of the index finger at
      the level of the metacarpophalangeal joint. The clinical examination and the
      operative findings allow us to conclude that the symptoms were due to tendinitis
      of the flexors of the index associated with fracture of the sesamoid and
      cartilaginous degenerative changes. We also present a review of the literature.

PMID- 16277152
TI  - [Aneurysmal bone cyst of the second metacarpal: technique of conservation of the
      metacarpophalangeal joint and short-term result. A case report].
AB  - The authors report an aneurismal bone cyst in the second metacarpal of a 16-year
      old patient. It was an aneurismal bone cyst of the agressive diffuse variety
      involving the proximal metaphyseal, diaphyseal and distal epiphyseal zones.
      Conservation of the MCP joint of the index was the priority. The authors report
      the technique used as well as the clinical and radiological results.

PMID- 16277153
TI  - [Bilateral proximal metaphyseal fracture of the humerus in a child. A case
      report].
AB  - A case of bilateral proximal metaphyseal fracture of the humerus in a 3 year-old
      child victim of a traffic road accident is presented. The fractures were managed
      conservatively under general anesthesia with an excellent remodeling at the
      fOllow-up of 2 years and 8 months.

PMID- 16277154
TI  - [Bizarre parosteal osteochondromatous proliferation (Nora's lesion). Two case
      reports].
AB  - Bizarre parosteal osteochondromatous proliferation, or Nora's tumor, is an
      uncommon lesion, involving mostly tubular bones of hands and feet, arising from
      the cortical surface. It must be distinguishable from chondrosarcoma, parosteal
      osteosarcoma and florid reactive periostitis. It is a benign lesion,
      characterized by a proliferation of chondroid, bony and fibrous tissues. The
      authors report two cases involving the hand. The diagnosis can be made thanks to
      imaging techniques and confirmed by histological examination. The treatment is
      surgical, namely complete excision but there is a high rate of local relapse.

PMID- 16277155
TI  - [Digital myxoma. A case report and review of the literature].
AB  - Myxoma is a benign mesenchymatous neoplasm, but can be locally invasive. We
      describe a rare case of digital myxoma managed in Antananarivo (Madagascar) main
      hospital. A 16 year-old young man had a 10 mm diameter myxoma located inside the
      flexor sheath next to the first phalanx of the left long finger. Surgical
      excision was curative, and there was no recurrence after two years follow-up. It
      is probably the first description of such a case.

PMID- 16277156
TI  - Expression of PCNA positivity in the brain of normal adult heterothermic
      vertebrates: further observations.
AB  - As part of our study of non-experimentally induced encephalic proliferation in
      unequivocally adult individuals of several heterothermic Vertebrates (Podarcis
      sicula, Triturus carnifex, Rana esculenta, Carassius carassius), we deal here
      with areas not considered in previous investigations, i.e. various encephalic
      regions (except the telencephalon) in Podarcis sicula, Triturus carnifex and Rana
      esculenta, the diencephalon and medulla oblongata in Carassius carassius, and the
      olfactory bulbs in the two Amphibians. In the previous and current research, we
      have used Proliferating Cell Nuclear Antigen (PCNA) as a marker. PCNA is a
      ubiquitous intracellular antigen of the cycline family (proteins that regulate
      the cell cycle), which acts as an auxiliary protein to DNA polymerase delta; it
      can be detected immunocytochemically with monoclonal antibodies to reveal cell
      cycle phases that coincide with DNA synthesis. Spontaneous proliferation events,
      revealed by PCNA positivity, were constantly present in this study, being
      substantial in the olfactory region and diencephalon, very modest in the
      mesencephalon and myelencephalon, and absent in the cerebellum. In particular,
      signs of proliferation were abundant in the epithelium lining the cavities of the
      olfactory bulbs, while they were of different magnitude in tracts (with multiple
      and comparatively different sites related to the dorsal and/or ventral thalami)
      of the ependyma that delimits portions of the III ventricle and also, in all the
      species examined, at the level of the preoptic and infundibular recesses. Such
      signs were rare in the ependymal epithelium of the mesencephalic ventricle in
      Podarcis sicula and the rhombencephalic ventricle in all four species examined.
      This immunoreactivity was also observed in extra-ependymal areas: in the internal
      granular layer of the olfactory bulbs in Triturus carnifex and Rana esculenta; in
      the diencephalic nuclei of the habenula in Podarcis sicula, in both Amphibians
      and in Carassius carassius; in the mesencephalic tectum in Podarcis sicula and in
      the two Amphibians. As in our previous studies, the current immunocytochemical
      picture revealed by PCNA positivity generally agrees with literature reports on
      the presence of normal proliferation in the areas investigated here. These
      literature sources consist primarily of the observations of Kirsche (1967),
      emerging from his preceding experimental investigations, and of confirmatory data
      from studies in subsequent decades by other researchers obtained with tests
      different from our marker. Nevertheless, the number of studies that deal with the
      species considered in the present research, or species closely related to them,
      is rather limited.

PMID- 16277157
TI  - Cytokeratin changes in cell culture systems of epithelial cells isolated from
      oral mucosa: a short review.
AB  - In the past three decades, many studies have analyzed ultrastructural and
      molecular markers of differentiation in squamous stratified epithelial tissues.
      In these tissues, epithelial cells migrating from the basal layer to the upper
      layers undergo drastic changes, which involve membrane-associated proteins, DNA
      synthesis, phenotypic aspects, lipid composition, and cytoskeletal components.
      Cytoskeletal components include a large and heterogeneous group, including
      intermediate filaments, components of the cornified envelope, and of the stratum
      corneum. When grown in mono- and multilayer cell cultures, epithelial cells
      isolated from the oral mucosa may reproduce many of the biochemical and
      morphological aspects of epithelial tissue in vivo. In the present paper, we
      examine phenotypic changes, development of suprabasal layer, and Involucrin
      expression occurring in differentiating oral epithelial cells, based on
      literature review and original data.

PMID- 16277158
TI  - Intercellular junctions in oral epithelial cells: ultrastructural and
      immunological aspects.
AB  - The activation of the molecular cascade leading to Ca++ -induced differentiation
      in cultured epithelial cells might be provided by the establishment of
      intercellular junctions between cells. In the present paper, we tested the
      hypothesis that Ca++ concentration would determine morphological and biochemical
      changes in intercellular junctions of cultured human gingival cells. Triplicate
      samples of monolayer cultures of human oral gingival cells were grown with two
      different Ca++ concentrations (0.3 and 1.8 mM), and examined by transmission
      (TEM) and scanning (SEM) electron microscopy at different time periods. To
      determine the role of the E-cadherin/beta-catenin complex in intercellular
      junction formation, oral epithelial cell cultures were grown in 0.3 mM Ca++ in
      presence of a blocking antibody anti human E-cadherin, stained with antibodies
      anti human beta-catenin, and examined by confocal laser scanning microscopy
      (CLSM). By TEM and SEM, cells grown at physiologic Ca++ concentrations (i.e., 1.8
      mM) showed a subjective increase of the size of microvilli and of the number of
      intercellular junctions, which was more evident after 3 days in culture.
      Desmosome-like junctions were observed in cells grown in 1.8 mM Ca++, not in
      cells grown in 0.3 mM. By CLSM, development of intercellular adhesion was marked
      by membranous localization of E-cadherin and beta-catenin within the first hours
      in both culture types. When cell-cell adhesion was prevented, cells showed round
      shape and no membranous localization of beta-catenin. Restoring cell adhesion
      brought about polygonal cell shape and membranous localization of beta-catenin.
      We can conclude that increased Ca++ concentration may determine biochemical and
      morphological changes at membranous level in human oral epithelial cells. These
      changes may facilitate the development of intercellular junctions.

PMID- 16277160
TI  - Main and accessory renal arteries--a morphological study.
AB  - The present work was undertaken to document the incidence of accessory renal
      arteries in kidney specimens obtained from subjects of Indian origin.
      Comprehensive dissection carried out in the dissection hall of Anatomy Department
      of All India Institute of Medical Sciences (India) on forty cadavers over a
      period of five years revealed a single main renal artery on either side in 80% of
      the specimens. The mean length of the main renal artery was 31.05 +/- 12 and 25.0
      +/- 9.5 mm on the right and the left side respectively. Multiple (accessory)
      renal arteries were observed in 20% of the specimens with unilateral anomaly
      (15%) being more commonly encountered than bilateral anomaly (5%). The mean
      length of the accessory renal artery was 36.4 +/- 10 and 36.6 +/- 11 mm on the
      right and the left side respectively. The accessory artery when present,
      invariably crossed the anterior aspect of the ureter. Familiarity about the
      possible variations in the renal arterial pattern are especially important for
      the personnel dealing with kidney retrieval and transplantation, various
      endourologic procedures and innumerable interventional techniques. In the
      majority of such situations, it is the comprehensive knowledge of the renal
      arterial pattern which remains the key issue in determining the technical
      feasibility of surgical interventions as well as the post operative management.

PMID- 16277159
TI  - In vivo effects of a novel degradable filler.
AB  - Novel types of permanent and transient fillers are proposed both in plastic and
      reconstructive surgery and in dermatology. Different molecules with high
      biocompatibility, no side effects, and slow degradation rate in human tissues are
      emerging. The importance of degradable fillers significantly increased in recent
      years for a variety of reasons: surgical injection of these materials is easier
      and with less side effects; treatment could be performed in a short time;
      patient's reported pain is scant; treatment-related expenses and cost for the
      patient are relatively low. In this study we investigated the biological effects
      of a new degradable filler, i.e. of a polymer made of 8% high grade (99%)
      polyvinylic alcohol, and of 92% sterile water in rat skin, after its injection in
      the dermis. The polymer examined exhibited optimal biocompatibility and full
      degradability in normal rat skin within 120 days. No pathological changes could
      be observed in the areas where injection of polymer had taken place.

PMID- 16277161
TI  - Autonomic and sensitive somatic innervation of the ostrich elbow and knee joints
      articular capsule.
AB  - The present research was carried out on the fibrous layer of the ostrich's elbow
      and knee joints articular capsule, employing opportunely modified gold chloride
      Ruffini's method, to study the autonomic and sensitive somatic nerve components.
      The distribution of both nerve components followed frequently the vascular
      networks. The autonomic innervation was represented by isolated or grouped
      ganglion cells, frequently placed along the course of nerve trunks, close to the
      epineurium or located within the perineural connective tissue. The sensitive
      somatic innervation was constituted by free and encapsulated corpuscles. The last
      one, morphologically classified as Pacini, Pacini-like and Golgi-Mazzoni's
      corpuscles, were found isolated or grouped to constitute simple and complex
      flower sprays, "opposito-polar corpuscles" and "poichilomorphous fibres". The
      very few Golgi-Mazzoni's corpuscles were found only in the knee joint articular
      capsule. The two nerve components, found in the considered districts, did not
      shown significant quanti-qualitative and topographic differences. This datum, at
      least in appearance, seems to conflict with the ostrich functional aptitudes. In
      fact, the ostrich is a bird unable to fly but very able to run.

PMID- 16277162
TI  - Hepatic osteodystrophy: does the osteoprotegerin/receptor activator of nuclear
      factor-kB ligand system play a role?
AB  - Multiple factors can contribute to the development of osteodystrophy in patients
      with chronic liver disease (CLD). Recently, two new cytokines, osteoprotegerin
      (OPG) and the receptor activator of nuclear factor-kB ligand (RANKL), have been
      implicated in the pathogenesis of postmenopausal osteoporosis and other metabolic
      bone diseases. Therefore, the aim of our study was to evaluate bone metabolism,
      bone mineral density (BMD) and OPG/RANKL system in 65 male patients with CLD and
      in 65 healthy controls. Our patients showed lower BMD values than controls both
      at lumbar and femoral levels. Moreover, they had an unbalanced bone turnover with
      an increased resorption phase, as shown by high levels of urinary
      deoxypyridinoline and a decreased formation phase, as shown by the slightly, but
      significant, low levels of bone-alkaline phosphatase. Patients showed lower
      plasma levels of free-testosterone than controls and higher - although not
      significantly so - plasma levels of 17 beta-estradiol. Furthermore, patients with
      CLD had higher levels of sex hormone-binding globulin and OPG, and lower levels
      of 25-hydroxyvitamin D (25-HOD) and IGF-I than the control group, while RANKL
      levels were similar in the two groups. In conclusion, our data do not confirm the
      hypothesis that the OPG/RANKL system could exert a key role in the pathogenesis
      of hepatic osteodystrophy, but rather that the observed increase in OPG levels
      may represent either the result of the inflammatory process per se or a
      compensation for the observed enhanced bone resorption.

PMID- 16277163
TI  - The evaluation of the Turkish version of the Well-being Questionnaire (WBQ-22) in
      patients with Type 2 diabetes: the effects of diabetic complications.
AB  - OBJECTIVE: Psychopathological conditions including depression and anxiety are
      important in patients with diabetes due to their negative effects on the quality
      of life, treatment and glycemic control. The specially designed questionnaire for
      diabetics, the Well-being Questionnaire (WBQ-22), was used to determine the
      psychological well-being in Turkish diabetic patients. METHOD: A total of 100
      patients, 45 males and 55 females, were included in the study. Patients completed
      WBQ-22 questionnaire. RESULTS: Sex, in-patient follow-up, age, duration of
      diabetes, form of treatment, diabetic microvascular complications, diabetic foot,
      and increased number of complications were the factors detected to have an effect
      on the scores of general well-being or its subscales. Scores of depression and
      general well-being were 7.10 +/- 3.82 and 39.74 +/- 12.27 in females, and 4.20 +/
      3.48 and 48.84 +/- 11.45 in males (p<0.05). Anxiety score was found to be 5.70
      +/- 3.71 in the outpatient clinic, and 7.28 +/- 4.38 in the inpatient clinics
      (p<0.05). General well-being score was 49.40 +/- 8.83 in patients having a
      diabetes duration of 1 yr or less and 33.70 +/- 8.83 in patients with 20 yr or
      more (p<0.05). Patients treated with insulin had depression score of 7.02 +/-
      4.07 whereas patients treated with diet had 4.50 +/- 3.27 (p<0.05). The
      increasing total chronic complication points were also found to have a negative
      effect on WBQ-22 scores. General well-being score was 51.08 +/- 9.84 in patients
      with no complications and 34.50 +/- 14.14 in patients with 4 complications
      (p<0.05). CONCLUSIONS: Psychosocial support should be provided to Type 2 diabetic
      patients by studying the psychological well-being with WBQ-22 questionnaire.

PMID- 16277164
TI  - Nationwide cross-sectional survey of 3560 children and adolescents with diabetes
      in Italy.
AB  - Clinical characteristics and metabolic control in a large cohort of children with
      Type 1 diabetes (T1DM) were evaluated. Fifty-three Italian centers for childhood
      diabetes collected blood samples and clinical records from 3560 consecutive
      eligible patients aged 1.6-17.10 yr with disease duration >12 months. HbA1c
      determinations were centralized in a Diabetes Control and Complications Trial
      controlled laboratory. HbA1c grand mean was 8.87 +/- 1.77%. Thirty-two percent of
      the patients had HbA1c values <8.0%. Puberty and disease duration were the main
      determinants of increase in HbA1c levels (<0.001). HbA1c values were inversely
      correlated to the frequency of blood glucose monitoring (p<0.001). Among the
      total population, 53.7% of the patients had 4 or more injections per day, 37.8%
      three injections, 7.4% < or =2 injections and only 1.1% was on pumps. Daily
      number of injections increased with age (p<0.001). Hypoglycemia episodes were
      reported in 17.6% patient-years and diabetic ketoacidosis (DKA) in 1.0% of
      children, more frequently in those with HbA1c >8.8% (p<0.02). Two thirds of
      Italian children with T1DM have HbA1c>8% despite regionalized centers,
      multidisciplinary team approach, free access to appropriate diabetes care,
      education, frequent blood glucose monitoring and multiple insulin injections.

PMID- 16277165
TI  - The effect of dexamethasone on gastric mucosal changes following sialoadenectomy
      in rat.
AB  - In this study, dexamethasone-induced gastric lesions were studied in rats that
      had undergone sialoadenectomy. The ultrastructural changes developed during the
      study were detected by electron microscopically, while blood serum and stomach
      epidermal growth factor (EGF) concentrations were measured by RIA. The result of
      the study showed that gastric lesions were correlated with gastric mucus
      secretion and both serum and mucosa EGF levels. After the administration of
      dexamethasone, it was found that sialoadenectomy significantly (p<0.01) raised
      the incidence of stomach lesions (p<0.01), and a significant increase in mucus
      secretion was also found. Additionally, the serum and gastric mucosal EGF levels
      fell after sialoadenectomy when compared to normal rats. The most important
      gastric mucosal changes were observed in rats treated with dexamethasone and
      those both sialoadenectomised and treated with dexamethasone.

PMID- 16277166
TI  - Evaluation of right and left ventricular function using pulsed-wave tissue
      Doppler echocardiography in patients with subclinical hypothyroidism.
AB  - Previous studies showed that subclinical hypothyroidism (SH) was associated with
      cardiovascular disorders, such as endothelial dysfunction, atherosclerosis and
      myocardial dysfunction. Only one study investigated left ventricular (LV)
      function using pulsed tissue Doppler echocardiography (TDE) in patients with SH.
      However, no study has used this technique in the identification of right
      ventricular (RV) function in these patients. We aimed to investigate the effect
      of SH on RV and LV function using TDE technique. The present study included 36
      newly diagnosed SH patients and 28 healthy controls. For each subjects, serum
      free T3 (FT3), free T4 (FT4), total T3 (TT3), total T4 (TT4), TSH, peroxidase
      antibody (TPOab) and thyroglobulin antibody (TGab) levels were measured, and
      standard echocardiography and TDE were performed. In patients with SH, TSH levels
      were significantly higher, and TPOab and TGab levels were significantly higher
      when compared to healthy controls. TDE showed that the patients had significantly
      lower early diastolic mitral and tricuspid annular velocity (Ea) and early/late
      (Ea/Aa) diastolic mitral and tricuspid annular velocity ratio (p<0.05, p<0.05 and
      p<0.001, p<0.001, respectively), and significantly longer isovolumetric
      relaxation time (IRT) of left and right ventricles (p<0.001 and p<0.001,
      respectively). However, Aa, Sa, and isovolumetric contraction time (ICT) and ET
      (ejection time) of left and right ventricle did not significantly differ (p=ns
      for all). In addition, a negative correlation between TSH and TD-derived
      tricuspid Ea velocity and Ea/Aa ratio, and a positive correlation between TSH and
      IRT of right ventricle were observed. Our findings demonstrated that SH is
      associated with impaired RV diastolic function in addition to impaired LV
      diastolic function.

PMID- 16277167
TI  - Acute changes in circulating hormones in older patients with impaired ventricular
      function undergoing on-pump coronary artery bypass grafting.
AB  - OBJECTIVES: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass
      (CPB) causes an acute stress response characterized by changes in the levels of
      several hormones, which might play a role in the high complication rate
      experienced by older patients after CABG. Thus, the aim of the study was to
      investigate changes in the circulating levels of anabolic and catabolic hormones
      in old people undergoing CABG with CPB. DESIGN: Intervention case study. METHODS:
      19 patients (12 males, 7 females) aged 70.1 +/- 6.1 yr (age range 62-80) with
      coronary artery disease and an ejection fraction <40% who underwent cardiac
      surgery. Cortisol (Cort), DHEA, DHEAS, LH, estradiol (E2), total testosterone
      (Te), SHBG, IGF-I were measured the day before, on the day of the procedure and
      1, 2, 3, 4, and 30 days after CABG. RESULTS: After surgery, serum IGF-I levels
      decreased (p<0.001), while levels of Cort, DHEAS and E2 significantly increased
      in both men and women. Alterations in Te levels differed between the two sexes
      with a significant decline in men and a significant increment in women.
      CONCLUSION: CABG with CPB resulted in a dramatic drop in Te levels in old men and
      a significant decline in IGF-I in both sexes. Serum Cort levels also
      significantly increased in both sexes. These hormonal changes may, at least
      partially, explain why the elderly need prolonged rehabilitation after CABG.

PMID- 16277168
TI  - Increased liver enzymes and hormonal therapies in girls and adolescents with
      Turner syndrome.
AB  - Elevated liver enzymes can be seen relatively frequently in patients with Turner
      syndrome (TS), while the pathogenesis of this remains unclear. Our
      epidemiological and prospective study aimed to investigate: a) the natural 2-yr
      course of liver disease in a selected cohort of young patients with TS, who had
      been preliminarily recruited on the basis of persistently elevated liver enzymes;
      b) the role of prolonged hormonal therapies in the etiology of liver dysfunction.
      From an overall population of 214 TS patients younger than 20 yr, only 19 (8.9%)
      were recruited, according to the following inclusion criteria: increased serum
      concentrations of one or more liver enzymes, exceeding the uppermost limit of the
      respective normal ranges, and persistence of these liver alterations for 6 months
      after the preliminary assessment. On the basis of the results of this prospective
      study, we can conclude that: a) the prevalence of liver abnormalities in girls
      and adolescents with TS is much lower and more strictly related to hormonal
      therapies than in TS adults; b) both autoimmunity and obesity are not frequently
      involved in the etiology of TS liver dysfunction; c) liver damage is either mild
      or moderate and its severity is not conditioned by karyotype; d) its course may
      be self-limiting; e) its natural history may be characterized in some cases by a
      slight deterioration of intrahepatic cholestasis, with no negative repercussions
      on liver synthetic function.

PMID- 16277169
TI  - Prevalence of goiter among schoolchildren from Gorgan, Iran, a decade after
      national iodine supplementation: association with age, gender, and
      thyroperoxidase antibodies.
AB  - BACKGROUND: One decade after universal salt iodization in Iran, goiter
      prevalence, urinary iodine concentration (UIC) and thyroperoxidase antibody
      (TPOAb) values were assessed among schoolchildren in Gorgan, Iran. METHODS: From
      2003-2004, 500 girls and 900 boys aged 7-11 yr were evaluated for goiter by
      palpation. UIC was measured in 183 randomly-selected goitrous children. Serum
      TSH, T4, and TPOAb were measured in 53 goitrous and 30 non-goitrous children with
      adequate UIC. RESULTS: Goiter was detected in 370 (26.4%) children. Goiter was
      present in 31% of girls and 17% of boys age 9 (p<0.012); 37% of girls and 20% of
      boys age 10 (p<0.003); and 52% of girls and 19% of boys age 11 (p<0.0001). Median
      (range) UIC for all goitrous children sampled was 190 (20-600) microg/l; 220
      (30590) in boys and 170 (20-600) in girls (p=0.001). Eight point seven percent of
      goitrous children and 22% of goitrous girls aged 10-11 had UIC<100 microg/l,
      while 47% of the goitrous children had UIC> or =200 microg/ l. TPOAb was present
      in 52.8% of goitrous children and 10% of non-goitrous children (p=0.0001). TPOAb
      was present in 53.9% of 10-11 and 22.7% of 7-9 yr old goitrous and non-goitrous
      children (p=0.003) with adequate UIC. Median (range) TSH was 2.9 (0.3-10.9) mlU/I
      in TPO-positive and 1.8 (0.5-4.1) in TPO-negative children (p=0.001).
      CONCLUSIONS: Gorgan, Iran, is an iodine-sufficient area and almost half of
      schoolchildren have more than adequate UIC. TPOAb is associated with endemic
      goiter. Despite sufficient UIC overall, some school-aged girls remain at risk of
      iodine deficiency.

PMID- 16277170
TI  - Multiple endocrine neoplasia type 2A/localized cutaneous lichen amyloidosis
      associated with malignant pheochromocytoma and ganglioneuroma.
AB  - We hereby present a rare variant of multiple endocrine neoplasia type 2A (MEN2A)
      associated with a rare skin disease primary cutaneous lichen amyloidosis and
      discrete malignant pheochromocytoma in both adrenal glands and pancreatic tail,
      and interestingly accompanied ganglioneuroma located in retroperitoneum in a 34
      yr-old female. The presence of composite tumor of pheochromocytoma and
      ganglioneuroma arising in the adrenal glands has been described previously in
      MEN2A and in sporadic cases. The patient displayed classical signs and symptoms
      of catecholamine excess. Biochemical screening proved pheochromocytoma. Computed
      tomography revealed multiple mass lesions in both adrenal glands. It also showed
      a large heterogeneous mass that clearly discriminated from right adrenal gland in
      retroperitoneal location. After surgical exploration, both adrenal glands and the
      suspicious mass in pancreatic tail were removed successfully together with
      subtotal resection of the retroperitoneal tumor. Histopathologic examinations
      confirmed the presence of pheochromocytoma in both adrenal glands as well as
      pancreatic lesion. A retroperitoneal ganglioneuroma was also present. Symptomatic
      and biochemical evidence of pheochromocytoma subsided after the operation.
      Further evaluation for medullary thyroid carcinoma and primary
      hyperparathyroidism confirmed MEN2A. Mutation analysis of the ret proto-oncogene
      revealed a missense point mutation at position 634 in exon 11, which gives rise
      to the substitution of a cysteine codon with a tyrosine residue.

PMID- 16277171
TI  - Multiple brown tumors of the ribs simulating malignancy.
AB  - Bone disease associated with primary hyperparathyroidism, known as osteitis
      fibrosa cystica, is now very rarely encountered, since the parathyroid disorder
      is most often diagnosed at the early stage of asymptomatic hypercalcemia. Here,
      we report the case of a patient with multiple pleural-based masses and
      hypercalcemia, which led to the presumptive diagnosis of malignancy. However,
      histological and laboratory data were consistent with the development of brown
      tumors of the ribs due to underlying severe hyperparathyroidism.

PMID- 16277172
TI  - Cyclic Cushing's disease with paradoxical response to dexamethasone.
AB  - Cyclic Cushing's disease is an unusual disorder characterised by ACTH-dependent
      periodical increase of serum cortisol levels, clinically accompanied by
      peripheral edema, abnormalities of cardiac rhythm and hypokalemia. The condition
      may be unrecognised for years, since the typical features of Cushing's disease
      are usually absent due to the intermittent and brief duration of cortisol
      hypersecretion. We describe the case of a 42-yr-old man with Cyclic Cushing's
      disease due to an ACTH-producing pituitary macroadenoma, who presented two
      episodes of hypercortisolism in a 3-yr-period, clinically characterised by
      peripheral edema, hypokalemia and arrhythmia. The diagnosis was suspected because
      of a paradoxical increase of plasma ACTH and cortisol after dexamethasone
      administration during an asymptomatic period and was confirmed by pituitary
      imaging and by final histology after transphenoidal resection of the pituitary
      adenoma. After surgery, the patient resumed a normal pituitary-adrenal function
      with restoration of the normal ACTH and cortisol suppression after dexamethasone.
      Cyclic Cushing's disease should be considered in the differential diagnosis of
      several conditions characterised by recurrent episodes of idiopathic edema,
      hypokalemia or unexplained cardiac arrhythmia. In such patients, the pituitary
      adrenal axis should be tested possibly during the acute phase of their disease or
      using the dexamethasone suppression test during asymptomatic intervals.

PMID- 16277175
TI  - Inadequate treatment causing fasting ketoacidosis in a patient with Addisonian
      crisis.

PMID- 16277176
TI  - [The Urological Clinic of the Charles University and of the General Teaching
      Hospital in Prague and 3 decades of its existence].

PMID- 16277177
TI  - [Comprehensive long-term analysis of hypospadias repair using vascularized flaps
      and tubularized incized plates--report on 588 cases].
AB  - BACKGROUND: The article presents a comprehensive long-term analysis of the modem
      hypospadias repair based on preservation and use of the urethral plate. METHODS
      AND RESULTS: In years 1987 to 2004, 476 patients (aged 8 months to 45 years) were
      operated using a praeputial (mostly) flap. 81% were indicated for reconstruction
      of a proximal form of hypospadias, mostly penile. In years 1986 to 1991, a
      tubularized flap was performed in 31 patients. Since 1992, an onlay island flap
      in 394 patients, inlay-onlay flap in 43 patients and onlay-tube-onlay flap in 8
      patients have been used. In years 2000 to 2004, 112 patients (aged 13 months do
      17 years) were operated using tubularized incised plate (TIP) repair, mostly
      because of distal form of hypospadias. To cover the neourethra, a dartos flap was
      used in 72 and spongioplasty in 37 patients. We achieved the primary healing in
      89% and 91%, resp., of patients after onlay and onlay-inlay island flap repairs
      with an average follow-up of 6,7 and 5,7 years, respectively. The most frequent
      complications were fistula or dehiscence of the glans. After the TIP repair
      combined with a dartos flap, 89% of the first operated patients healed without
      complications with an average follow-up of 2.3 years. A higher complication rate
      (40%) was found after a spongioplasty with foreskin preservation. Secondary
      repairs were also associated with more complications. CONCLUSIONS: Using onlay
      and inlay-onlay one-stage repairs, or using TIP one-stage repair combined with a
      dartos flap, a successful primary hypospadias repair was achieved in 90% of
      patients. The definite repair should be completed during early childhood.

PMID- 16277174
TI  - Cardiovascular risk in aging and obesity: is there a role for GH.
AB  - GH has significant impact in adults. In fact, patients with the GH deficiency
      (GHD) syndrome are now recognized as having an increased cardiovascular risk. The
      effects of human aging on GH secretion have been evaluated by a number of
      researchers. Studies of 24 h secretion of GH have shown variable reductions in
      most 24-h GH secretory parameters in middle-aged and in older men and women,
      resulting in a decrease in plasma levels of its anabolic mediator IGF-I. Obesity
      is also associated with several endocrine and metabolic abnormalities. These
      include decreased serum GH concentrations, reduced GH half-life, frequency of GH
      secretory episodes and daily GH production rate. The mechanism of the low GH in
      obesity is not completely understood nor is it clear whether its relationship
      with visceral adiposity is causal. The aim of this article will be to review the
      available clinical data concerning the potential involvement of "subclinical" or
      perhaps better "functional" GHD, which is observed in aging and obesity, in the
      increase in cardiovascular risk which characterizes these two conditions.

PMID- 16277173
TI  - Glucagon-like peptide 1 (GLP-1) and metabolic diseases.
AB  - Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone, mainly secreted
      after meals, which enhances glucose-induced insulin secretion and induces
      satiety. It has been reported that GLP-1 levels after a mixed meal and after an
      oral glucose load are reduced in patients with Type 2 diabetes. The reduction of
      oral glucose-stimulated active GLP-1 levels in patients with Type 2 diabetes has
      also been observed during euglycemic iperinsulinemic clamp. The reduction of post
      prandial circulating active GLP-1 in Type 2 diabetic subjects, as a consequence
      of chronic hyperglycemia, could contribute to the reduction of early post
      prandial insulin secretion; in fact, the administration of GLP-1 receptor
      antagonists to healthy volunteers elicits both an impairment of meal-induced
      insulin secretion and an increase of post-prandial glycemia similar to that
      observed in Type 2 diabetes. GLP-1 is rapidly inactivated by dipeptidyl peptidase
      IV (DPP-IV), an enzyme produced by endothelial cells in different districts and
      that circulates in plasma. It is still not clear whether the reduction of mealor
      oral-glucose stimulated GLP-1 levels in Type 2 diabetic patients is due to
      impairment of secretion, increase of degradation, or both. The major limitation
      of using GLP-1 to treat diabetic patients is the short half-life of the native
      compound. There are now several compounds in various stages of pre-clinical or
      clinical development for the treatment of Type 2 diabetes that utilize the GLP-1
      signaling pathway; these include GLP-1 receptor agonists with extended half
      lives, and inhibitors of DPP-IV that increase circulating levels of endogenous,
      intact and bioactive GLP-1.

PMID- 16277178
TI  - [Role of laparoscopy in uro-oncology].
AB  - The article reviews problems of laparoscopic surgery in uro-oncology. Examples
      supporting and opposing the laparoscopic alternative are given. Original
      objections against the use of the method for the treatment of malignancies are
      discussed from the retrospective position. According to the predominant views it
      looks that laparoscopic treatment by a highly educated team with good technical
      background, respecting oncologic and functional aspects, does not have worse
      short-term and long-lasting results. The improving diagnostics and possibility to
      identify malignancies in early stage of development will enable wider use of the
      laparoscopic surgery.

PMID- 16277179
TI  - [Fluorescence cystoscopy in the diagnostics and treatment of superficial urinary
      bladder tumors].
AB  - BACKGROUND: 5-aminolevulinic acid induced fluorescence cystoscopy can detect more
      tumour lesions comparing to standard cystoscopy. The goal of our study was to
      assess the influence of fluorescence cystoscopy used during transurethral
      resection on the recurrence rate and the length of tumor-free interval in stage
      Ta, Tl transitional cell carcinoma of the urinary bladder. METHODS AND RESULTS:
      In prospective randomized study 109 patients with primary or recurrent stage Ta
      Tl bladder transitional cell carcinoma treated with transurethral resection were
      enrolled. 17 patients with high grade tumors were evaluated separately. In group
      A the transurethral resection was performed with standard white light endoscopy,
      in group B with fluorescence cystoscopy. The patients were followed using
      standard cystoscopy and urinary cytology. Recurrence free interval was evaluated
      in whole groups and also for single and multiple and for primary and recurrent
      tumors separately. The median time to recurrence was 8.05 months in group A and
      was significantly shorter than 13.54 months in group B (p = 0.04, log-rank test).
      In separate analyses the median time to recurrence was significantly shorter
      using fluorescence cystoscopy in multiple (p = 0.004) and in recurrent (p = 0.02)
      tumors, but not in solitary and primary tumors. CONCLUSIONS: 5-aminolevulinic
      acid induced fluorescence cystoscopy used during transurethral resection reduces
      the early recurrence rate in stage Ta Tl bladder transitional cell carcinoma.

PMID- 16277180
TI  - [Female sexual dysfunction].
AB  - Female sexual dysfunction (FSD) is a disorder with relatively high incidence in
      the community. Its incidence in age-dependent and it can significantly limit the
      quality of life of women concerned. Dysfunction, as a multicausal and
      multidimensional problem, it comprises biological, psychological and
      interpersonal factors. Disorders are listed according to a sexual desire,
      arousal, experiencing an orgasm and pain incidence. Authors summarized data on
      incidence, diagnosis and therapy of this disorder.

PMID- 16277181
TI  - [Interstitial cystitis--its diagnostics and treatment].
AB  - Interstitial cystitis is a chronic, non-bacterial inflammatory disorder of the
      wall of the urinary bladder and it manifests with very painful symptoms.
      Initially it can resemble a bacterial inflammation of the urinary bladder. This
      syndrome is characterised with motor and sensory dysfunction of the urinary
      bladder. The difficulties can be classified into so-called syndrome of the
      chronic pelvic pain. Increasing incidence, chronicity of this disorder and
      specific treatment leads to the reinterpretation of the chronic inflammation of
      the urinary tract diagnosed in the past and to the modification of the treatment
      of these patients. Because of the polymorphic difficulties and the psychosomatic
      manifestations, IC can lead to invalidity of the patient.

PMID- 16277182
TI  - [Expression of PAX2 and PAX8 genes in conventional type of renal carcinoma and
      their role in the tumor prognosis].
AB  - BACKGROUND: Sporadic renal cell carcinoma is one of the most common kidney
      malignancies in adults (85%). According to the IARC (The International Agency of
      Research on Cancer) Czech Republic has the first world position in the incidence
      and mortality for RCC. The prognosis of RCC is very poor because of high
      mortality around 70 to 50% and unpredictable progression after tumor removal.
      More precise molecular prognostic markers are required. Genes PAX2 and PAX8
      control cell division during embryonic development and plays crucial role in
      tumor development because of stimulation of cell proliferation and/or inhibition
      of apoptotic program. METHODS AND RESULTS: Our RCC sample collection contains 64
      tumor samples and 10 "normal" renal samples extracted from the affected kidney.
      mRNA was isolated from all samples and converted into cDNA. Expression of PAX
      genes was analyzed by using relative quantification real-time PCR with TaqMan
      labelled probe and GAPDH gene as an endogenous control. CONCLUSIONS: Expression
      of PAX2 gene was found in 97% and expression of PAX8 gene was found in 89% of
      analyzed tumor samples. The expression of both target genes was found in all
      "normal" renal samples. The level of expression of both PAX genes was very
      variable with the range from hundred times lower to forty times higher in
      comparison with the expression of chosen endogenous control. There were found no
      correlations between the expression of target genes and clinical-histological
      markers. These results do not have prognostic value yet because of short duration
      of patient observation. Follow-up clinical data are essential for completion of
      this research.

PMID- 16277184
TI  - [Treatment alternatives of the locally advanced prostate cancer].
AB  - Author makes overview on locally advanced prostate cancer. In spite of the effort
      to make diagnosis in the earliest stage, disease is still pretty often diagnosed
      in locally advanced stage with significantly higher risk of progression and
      recurrence. He summarizes current view on available treatment alternatives
      (radical surgery, radiotherapy, hormonal treatment, chemotherapy) and their
      possible and proven combinations. Monotherapy is not considered as the optimal
      alternative, treatment of choices is the multimodal treatment strategy, though
      some combinations have been already confirmed as inappropriate.

PMID- 16277183
TI  - [Molecular nature of renal tumours of adults].
AB  - Significant progress has been achieved recently in the cytogenetic and molecular
      research of the kidney parenchymal tumors which incidence has been steadily
      increasing in the developed countries. Renal cancer is an important clinical
      problem, still without effective therapy. The accuracy of current diagnosis,
      prognosis of the disease and the effectiveness of the treatment are limited by
      the poor understanding of its cytogenetic and molecular pathogenic mechanisms. In
      this review we summarize up to date cytogenetic alterations and gene expression
      profiles of the most important tumor genes, focusing at the classification of
      parenchyma tumors of adult patients.

PMID- 16277185
TI  - [Treatment of the lower pole nephrolithiasis].
AB  - BACKGROUND: The purpose of the study was to compare the efficacy of
      extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy for lower
      pole nephrolithiasis. METHODS AND RESULTS: We retrospectively analyzed results of
      lower pole nephrolithiasis treatment in 396 patients (221 treated by
      extracorporeal shock wave lithotripsy and 175 by percutaneuos nephrolithotomy).
      We evaluated results of the treatment in the 3 months interval after the
      procedure in groups classified according to the stone size: <10 mm, 10-20 mm, >20
      mm. Stone free status was achieved in these groups after 96 (66%), 43 (38 %) and
      2 (25%) shock wave lithotripsies and 48 (84%), 75 (76%) and 25 (74%) percutaneous
      nepholithotomies. The efficacy irrespective of insignificant residual fragments
      (< 4 mm) was in 176 (66%) lithotripsies and 156 (82%) single percutaneuos
      nephrolithotomies. CONCLUSIONS: Percutaneous nephrolithotomy is more effective
      methods in the treatment for lower pole nephrolithiasis than extracorporeal shock
      wave lithotripsy especially for stone size >10 mm.

PMID- 16277186
TI  - [Effect of biofeedback in the treatment of voiding dysfunction].
AB  - BACKGROUND: Biofeedback represents a treatment option for children with voiding
      dysfunction characterised with poor pelvic floor relaxation. METHODS AND RESULTS:
      Thirty nine children with symptoms of voiding dysfunction were treated in BFB
      program. Average number of sessions to achieve good response was three. Follow up
      was 12 to 24 months. Very good clinical response was obtained in 55, 7% of
      patients, who were characterised by cessation or resolution of incontinence in
      66, 7%, dyscoordination in 57, 6% and urinary tract infection in 41, 1% of
      children. CONCLUSIONS: Biofeedback therapy is an effective method for treating
      poor pelvic floor relaxation. It helps to improve coordination of the detrusor
      and external sphincter function and it accelerates voiding reflex maturation.

PMID- 16277187
TI  - What Katrina teaches us about rules & structures.

PMID- 16277189
TI  - Salary slowdown reported for specialists.

PMID- 16277188
TI  - Plans ready to go all out for Part D.

PMID- 16277190
TI  - The lure of tax reform.

PMID- 16277191
TI  - Just how will CDHC change your job?

PMID- 16277192
TI  - What docs hate most about plans.

PMID- 16277193
TI  - Cover dietary supplements? Some plans say yes.

PMID- 16277194
TI  - 17 alpha-hydroxyprogesterone caproate (17P) usage in a Medicaid managed care plan
      and reduction in neonatal intensive care unit days.
AB  - PURPOSE: To evaluate whether providing 17 alpha-hydroxyprogesterone caproate
      (17P) to high-risk pregnant women who have a history of preterm delivery in a
      Medicaid managed care population reduces the rate of neonatal intensive care unit
      (NICU) admissions, NICU length of stay, and associated costs. DESIGN: A 2004-2005
      longitudinal review of birth outcomes in 24 pregnant women with a history of
      preterm delivery who were treated with 17P versus a control group. METHODOLOGY:
      Intervention included offering 17P as a benefit to pregnant women who had a
      history of preterm labor and delivery and who were deemed to be appropriate
      candidates for this treatment by their physicians. An educational program about
      17P was developed that was aimed at physicians, their office staff, and plan
      members. A process of early identification of potential 17P candidates was also
      implemented. PRINCIPAL FINDINGS: NICU admission rates decreased to 14.3 percent
      in the control group and 8.3 percent in the 17P group. NICU length of stay
      decreased significantly from 231 days in the control group to 149 days in the 17P
      group. Overall costs for the control group were dollar 568,462 versus dollar
      165,487 in the treatment group--a significant savings of dollar 402,975.
      CONCLUSION: Offering 17P as a benefit to pregnant women enrollees with a history
      of preterm delivery can decrease NICU days significantly for a Medicaid managed
      care plan.

PMID- 16277195
TI  - Restrictive formularies may be contagious.

PMID- 16277196
TI  - Health plans pay less when PBM owns mail-order pharmacy.

PMID- 16277197
TI  - Incretin hormones poised for better control of diabetes.

PMID- 16277198
TI  - Medtronic, early adopter of CDHP, more than satisfied with result.

PMID- 16277199
TI  - Rx trend moderates while PPO costs increase.

PMID- 16277200
TI  - [Effect of afobazole on transmembrane ion currents in mollusk neurons].
AB  - The effect of anxiolytic afobazole (2-[2-morpholino)ethylthio]-5
      ethoxybenzimidazole dihydrochloride) at concentrations of 1, 10, 100 and 1000
      microM on transmembrane calcium, sodium, and potassium (slow and rapid) ion
      currents in isolated neurons of Lymnaea stagnalis mollusks have been
      investigated. Afobazole was found to produce a dose-dependent reversible action:
      the drug increased all ion currents at concentrations below 100 microM and
      inhibited all ion currents at concentrations from 100 to 1000 microM. Afobazole
      at high concentrations accelerated the inactivation of slow potassium ion current
      and reversibly inhibited the fast potassium ion current.

PMID- 16277201
TI  - [A comparative study of the development of drug differentiation between mexidol
      and phenazepam].
AB  - Interceptive stimulus properties of mexidol (50 and 100 mg/kg, i.p.) and
      phenazepam (2 mg/kg, i.p.) were compared using the standard operant model of
      liquid-reinforced drug discrimination (DD) procedure in male albino rats.
      Successful DD development has been shown in 100% of phenazepam-pretreated rats,
      while only 10% of mexidol-treated animals demonstrated DD. In the case of a high
      stimulus control, both mexidol and phenazepam DD manifestations showed high
      reproducibility (not less than 80% adequate reactions) and stability. The results
      suggest that mexidol, while possessing interceptive stimulus properties, belongs
      to the group of moderately discriminated psychotropic drugs.

PMID- 16277202
TI  - [Noopept improves the spatial memory and stimulates prefibrillar beta-amyloid(25
      35) antibody production in mice].
AB  - The effects of the novel proline-containing nootropic and neuroprotective
      dipeptide noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) were
      studied on NMRI mice upon olfactory bulbectomy, which had been previously shown
      to imitate the main morphological and biochemical signs of Alzheimer's disease
      (AD). The spatial memory was assessed using the Morris (water maze) test; the
      immunological status was characterized by ELISA with antibodies to prefibrillar
      beta-amyloid(25-35), S100b protein, and protofilaments of equine lysozyme, which
      are the molecular factors involved in the pathogenesis of AD. The control (sham
      operated) animals during the Morris test preferred a sector where the safety
      platform was placed during the learning session. Bulbectomized animals treated
      with saline failed to recognize this sector, while bulbectomized animals treated
      with noopept (0.01 mg/kg for 21 days) restored this predominance, thus
      demonstrating the improvement of the spatial memory. These animals also
      demonstrated an increase in the level of antibodies to beta-amyloid(25-35)--the
      effect, which was more pronounced in the sham-operated than in bulbectomized
      mice. The latter demonstrated a profound decrease of immunological reactivity in
      a large number of tests. Noopept, stimulating the production of antibodies to
      beta-amyloid(25-35), can attenuate the well-known neurotoxic effects of beta
      amyloid. The obtained data on the mnemotropic and immunostimulant effects noopept
      are indicative of good prospects for the clinical usage of this drug in the
      therapy of patients with neurodegenerative diseases.

PMID- 16277203
TI  - [Estimating the potential of antioxidant therapy for patients with Parkinson's
      disease diagnosis].
AB  - The efficiency of using the natural antioxidant mexidol in a combined therapy of
      Parkinson's disease has been evaluated in a group of 65 patients including 29
      females and 36 males. The drug was administered in the form of infusions (4-ml of
      a 5% solution per 200 - 250 ml of physiological solution) over a period of 10
      days. The clinical dynamics was evaluated in terms of the universal parkinsonism
      disease rate scale (UPDRS) and using the data of electromyography and
      electroneuromyography. The 10-day treatment led to a reliable decrease in the
      level of postural tremor and static tremor, a decrease in the muscle tone, and an
      increase in the mobility and locomotor activity of patients. The maximum positive
      effect of mexidol was observed for patients in the initial stage of disease with
      tremor as predominant clinical syndrome. Neurophysiological evidence of the
      efficacy of mexidol therapy included a decrease in the level of volley activity
      manifested in the electromyograms and a decrease in the velocity of conduction
      over peripheral motor nerve fibers.

PMID- 16277204
TI  - [Cardioprotective action of ferulic acid upon heart under stressor damage
      conditions].
AB  - Ferulic acid produces a pronounced protective antistressor effect and reduces
      both the stomach mucous membrane damage and the myocardium injury caused by
      painful immobilizing stress. The observed effect can probably be explained by the
      ability of ferulic acid to inhibit the process of lipid peroxidation and to
      increase the antioxidant activity in myocardium.

PMID- 16277205
TI  - [Changes in heart rate variability in healthy humans of different chronotypes
      under the action of melatonin].
AB  - In two weeks after termination of the administration of epiphyseal hormone
      melatonin, young healthy human volunteers of different chronotypes showed
      adaptive shifts in heart rate variability (manifested by ECG periodograms). It is
      suggested that pineal hormone can be used for stabilizing the vegetative state in
      healthy humans.

PMID- 16277206
TI  - [Effect of sodium-rich diet and captopril on the functional state of kidney in
      rats with experimental hyperthyreosis].
AB  - The administration of thyroxin (10 microg/100 g body weight, 7 days) in rats
      leads to an increase in the renal excretion of proteins and nitrates. Under the
      conditions of hypo- and normosodium diet, thyroxin decreased the rate of
      glomerular filtration. Hypersodium diet and captopril increased the rate of
      glomerular filtration in rats with experimental hyperthyreosis. The maximum level
      of renal excretion in hyperthyreoidal rats was observed on the background of
      sodium-rich diet.

PMID- 16277207
TI  - [Effect of karphedone on reproduction function in female rats].
AB  - Karphedone treatment (50 mg/kg over a period of two weeks) increased the ovary
      weight coefficient and increased the gestation index in female rats, while not
      affecting the terms of pregnancy and the characteristics of embryo development.
      At the same time karphedone decreased nicotinic cholinoreceptor mediated CNS
      activity, but produced no dopaminergic action.

PMID- 16277208
TI  - [The effects of no synthase blocker, no donor, and exogenous prostaglandins E2
      and F2alpha on murine oocytes].
AB  - Nitric oxide (NO) has emerged as one of several important intraovarian regulatory
      factors. Although the importance of NO has been demonstrated during gestation,
      its role in oocyte meiotic maturation (MM) is incompletely clear. In this
      context, the effects of nitric oxide synthase (NOS) blocker (N-omega-mono-methyl
      L-arginine, L-NMMA), NO donor (sodium nitroprusside, Na-NP), and exogenous
      prostaglandins (PGs) F2alpha and E2 on the MM of oocytes in mice have been
      studied. The exogenous PGs in a dose of 3.00 microg/kg inhibited the MM of murine
      oocytes. The effect of L-NMMA on the MM of oocytes was studied for the first time
      depending on the size of a follicle from which they were isolated. The maximum
      inhibition was observed for oocytes isolated from small follicles. Na-NP induced
      an increase in the number of oocytes from small (p < 0.01) and medium (p < 0.05)
      follicles, capable of forming polar bodies after a 20-h cultivation. The
      introduction of PG F2alpha to the test animals pretreated with L-NMMA potentiated
      the inhibition of MM. The NO donor decreased the inhibiting effect of PG F2alpha
      on the MM of oocytes isolated from small (p < 0.05) and medium (p < 0.05)
      follicles. The results confirm that NO/NOS ovarian system is involved into the
      mechanism of the PG action on the MM of murine oocytes and, probably, that NO is
      involved into the general mechanism of PG activity. In this case, PG, F2alpha can
      operate through nongenomic stimulation of membrane/endocellular mediators, where
      NO also acts as a mediator.

PMID- 16277209
TI  - [The effect of colcichine and iodine-lithium-alpha-dextrin on the phagocytosis of
      granulocytes and monocytes in patients with familial Mediterranean fever].
AB  - Disturbances in the regulation of phagocytic activity of neutrophils and
      monocytes (PANM) in whole peripheral blood of patients with familial
      Mediterranean Fever (FMF), which had not received treatment with colchicines,
      were determined by quantitative flow cytofluorimetry. The effect of iodine
      lithium-alpha-dextrin (armenicum) and colchicine on the PANM in the blood of FMF
      patients was studied in vitro. The intensity of phagocytosis in populations of
      neutrophils and monocytes in FMF patients (n = 6) during the remission period is
      higher than that during the FMF attack (n = 6) and higher than in healthy donors
      (n = 9). The PANM in patients during the FMF attack is higher compared to that in
      healthy donors. Iodine-lithium-alpha-dextrin (armenicum) and colchicine inhibited
      the phagocytosis of effector cells in FMF patients in a dose-dependent and time
      dependent manner. It was shown that the suppressive effect of the drugs increased
      with decreasing bacteria/effector cells ratio.

PMID- 16277210
TI  - [Pharmacological modulation of phagocytosis of granulocytes and monocytes in
      patients with familial Mediterranean fever].
AB  - Disturbances in the regulation of phagocytic activity of neutrophils and
      monocytes (PANM) in whole peripheral blood of patients with Familial
      Mediterranean Fever (FMF), which had not receive treatment with colchicines, and
      the effect of drugs from various pharmacological groups on the PANM in the blood
      of these patients were studied in vitro by quantitative flow cytofluorimetry. A
      comparative study of the drug action showed that the most effective PANM
      inhibitors during FMF are colchicine and iodine-lithium-alpha-dextrin
      (armenicum), while synthetic glucocorticoids and sodium thiosulfate showed low
      activity and produced no significant effect. It was established that armenicum is
      capable of modulating the PANM-inhibition effect of colchicine, neutralizing the
      effect of TNF, and increasing the effect of glucocorticoids. was observed. Sodium
      thiosulfate produces inhibition of the activity of armenicum.

PMID- 16277211
TI  - [Effect of carnosine and its combination with essentiale on lipid peroxidation
      and work capacity of experimental animals].
AB  - The effects of carnosine and its combination with essentiale on the processes of
      lipid peroxidation (LPO) and on the work capacity have been studied in mice. The
      administration of camosine, essentiale, and vitamin E, increased the work
      capacity of laboratory mice to a different extent, the effect being most
      pronounced for a mixture of carnosine and essentiale. Carnosine in the dose range
      studied exhibited a pronounced antioxidant effect with respect to LPO and
      optimized the potential of the organism in the course of intensive physical
      activity. This drug is not a doping and can be recommended as a means of
      improvement of the physical capacity.

PMID- 16277212
TI  - [The influence of cytaphate on the status of oxidative metabolism in rats with
      diabetic nephropathy].
AB  - The antioxidant effect of cytaphate (0,0-dimethyl-N-cytisinyl phosphate) has been
      studied in outbred white rats with alloxan-induced insulin-dependent diabetes
      mellitus. The content of malonic dialdehyde, diene conjugates, ketodienes, middle
      weight molecules, primary and secondary products of lipid peroxidation (LPO), and
      Schiff bases and the activity of catalase, glutathione peroxidase, and adenosine
      deaminase in erytrocytes have been evaluated. The state of oxidative protein
      modification, the content of malonic dialdehyde and diene conjugates, and the
      superoxide-anion production in the blood plasma have been determined. In the
      blood of animals with model diabetes, the LPO and oxidative protein modification
      processes were intensified and the level of superoxide anion production was
      increased. The administration of cytaphate led to a decrease of the LPO intensity
      and oxidative protein modification and to normalization of the level of
      superoxide anion production and the activity of enzymes involved in the
      antioxidant protection system.

PMID- 16277214
TI  - [Daphnia magna Straus: a test object for the pharmacological evaluation of GABA
      ergic drugs in the whole organism].
AB  - The toxicity of a series of GABAlytics (11 drugs) representing different
      pharmacological groups was evaluated in comparative experiments on Daphnia magna
      Straus and white mice. A high degree of correlation was established between the
      toxicity of GABA antagonists studied in daphnia and mice. The pharmacological
      analysis of the interaction of agonists and antagonists of
      GABA/benzodiazepine/ionophore-receptor complex--the competitive ligands for
      various binding sites--was carried out. It is suggested that the ability of GABA
      agonists to prevent the action of GABA antagonists in whole organism is mainly
      determined by their pharmacokinetic and pharmacodynamic features, rather than by
      direct competition for binding sites within the receptor complex.

PMID- 16277213
TI  - [Effect of Bergenia crassifolia extract on specific immune response parameters
      under extremal conditions].
AB  - The influence of a dry extract from Bergenia crassifolia (Fritsch) on the
      specific immune response parameters was studied under extremal conditions of
      model immunodepressive states induced by immobilization stress or
      cyclophosphamide injections. The drug produced normalizing effect on the content
      of antibody-forming cells in the spleen of experimental mice under the conditions
      of humoral response stimulation by antigen and in both immunodepression models.
      The bergenia extract decreases expression of inflammatory processes under delayed
      hypersensitivity reaction conditions, by preventing the accumulation of T
      lymphocytes in the inflammation focus and reducing the ability of cells to
      produce anti-inflammatory cytokines.

PMID- 16277215
TI  - [Pharmacogenomics: way to individual therapy].
AB  - Problems pertaining to the development of individual therapy based on the
      achievements of modern pharmacogenetics and pharmacogenomics, as well as the
      safety of using drugs from various pharmacological groups in patients belonging
      to different ethnical groups (with the corresponding features of metabolism) are
      considered. The terms "pharmacogenetics" and "pharmacogenomics" are discussed in
      connection to the significance of genetic polymorphism (or single nucleotide
      polymorphism) in determining of the individual sensitivity with respect to
      certain drugs.

PMID- 16277216
TI  - [Possible mechanisms of the antianginal action of GABA derivatives].

PMID- 16277217
TI  - [Antihypoxant activity and mechanisms of action of some natural and synthetic
      compounds].
AB  - The role of hypoxia as one of the main factors in the development of various
      pathologic processes is discussed. The anthihypoxic efficacy and mechanisms
      action of synthetic drugs (oliphen, amtizole, mexidol) and some polyphenolic
      agents of plant origin are considered. Among the mechanisms of antihypoxant
      action of these drugs, an especially important role belongs to the stimulation of
      expression of heat shock proteins and hypoxia-induced factors, which increase the
      stability of organism under the conditions of oxygen insufficiency.

PMID- 16277218
TI  - [Comprehensive approach from the standpoint of medical and traffic factors].

PMID- 16277219
TI  - [The lateral approach].

PMID- 16277220
TI  - [Serum S-100B protein and neuron-specific enolase after traumatic brain injury].
AB  - OBJECTIVE: The aim of this study was to investigate S-100B protein and NSE as a
      serum marker of brain cell damage after traumatic brain injury. MATERIAL AND
      METHODS: Forty-one patients with traumatic brain injury were included in this
      prospective study. Venous blood samples for S-100B protein and NSE were taken
      after admission and on the next day. Serum levels of S-100 protein and NSE were
      compared with Glasgow Coma Scale score, computed tomographic findings and outcome
      after 3 months. RESULTS: Serum S-100B protein and NSE were significantly
      correlated with Glasgow Coma Scale score and outcome after 3 months. The
      significant correlation was found between the initial S-100B and NSE (P < 0.001).
      In patients without parenchymal injuries on computed tomographic scan such as
      epidural hematoma and concussion, the elevation of S-100B protein and NSE was
      observed. The initial values of S-100B and NSE in acute subdural hematomas with
      unfavorable outcome were significantly higher than in those with favorable
      outcome. Secondary increase of serum markers was associated with the presence of
      secondary insult such as hypoxia or hypotension, and was found to have an
      unfavorable outcome. CONCLUSIONS: Serum concentration and kinetics of S-100B
      protein and NSE provide the clinical assessment of the primary brain damage and
      have a predictive value for outcome after traumatic brain injury.

PMID- 16277221
TI  - [A case of a dramatic recovery of hypertensive hemorrhage in the mid-pons].
AB  - A 50-year-old female who had a past history of non-treated hypertension,
      demonstrated a coma on arrival. CT revealed a high density lesion measuring 23 mm
      in transverse diameter and 15 mm in height at the ventral mid pons without
      breaking into a fourth ventricle or extending to the midbrain. She required
      mechanical ventilation support. Her consciousness improved on the 2nd hospital
      day. She showed tetra-plegia, which was especially dominant on her right side.
      Her symptoms gradually improved until she could stand and she was eventually
      discharged on the 41st hospital day. At 90 days after the initial presentation,
      an enhanced head MRI showed the absorption of the hematoma and no existence of
      any vascular malformation was observed. We herein report a case who dramatically
      recovered from a hypertensive pontine hemorrhage, despite the fact that she
      demonstrated several risk factors for a poor prognosis. The fact that the size of
      the hematoma was not so huge, and the location of the hematoma spared both the
      ascending reticular activating system and the nuclei, may explain the favorable
      outcome in this case.

PMID- 16277222
TI  - [A case involving complete removal of C2 dumbbell type neurinoma with
      preservation of the surrounding supportive tissue].
AB  - We report a case in which C2 neurinoma was completely removed with preservation
      of the surrounding supportive tissue. A 47-year-old female was admitted to our
      hospital with gait disturbance and spinal tumor identified in other hospital.
      Neurological examination on admission revealed hyperreflexia in bilateral limbs
      and pathological reflexes. Cervical plain X-radiography showed erosion of the
      left C2 lamina. Axial Gd-enhanced T1 weighted magnetic resonance (MR) images
      showed partial enhancement of a dumbbell shaped tumor at the C1-2 level,
      revealing compression of the spinal cord to the right and extending to postero
      laterally, and coronal MR images demonstrated that the tumor was clearly
      surrounded by the semispinalis capitis, semispinalis cervicis and inferior
      oblique muscles. The tumor was resected through a posterior approach without
      injuring the surrounding supportive tissue. Post operatively, she did not
      complain of nuchal pain during neck movement. After a 6-month follow-up period,
      cervical plain X-radiography showed preservation of cervical alignment, and
      coronal Gd-enhanced T1-weighted MR images demonstrated preservation of the
      posterior group of cervical muscles. It is desirable to preserve the surrounding
      supportive tissue as far as possible in order to minimize the postoperative neck
      pain and instability of cervical spine, like this case.

PMID- 16277223
TI  - [A case of intracranial dural arteriovenous fistula presenting with brainstem
      infarction].
AB  - A 68-year-old female presented with the disturbance of brainstem function. Brain
      T2 weighted and FLAIR (fluid-attenuated inversion recovery) magnetic resonance
      imaging revealed the hyperintensity signal of the medulla oblongata, which led to
      diagnosis of brainstem infarction. Diagnostic cerebral angiography showed the
      dural arteriovenous fistula (DAVF) developed on the left transverse sinus (TS).
      Venous drainage route was consisted of retrograde leptomeningieal venous reflux
      of the cerebrum and spinal perimedullary vein via superior petrosal sinus. Venous
      hypertension of the brainstem was relieved by transvenous platinum coil selective
      embolization of superior petrosal sinus. The correct analysis of venous drainage
      pattern is essential for the curative endovascular surgery.

PMID- 16277224
TI  - [A case of secondary anterior fossa dural arteriovenous fistula following
      posterior fossa craniotomy].
AB  - The etiology of dural arteriovenous fistula (AVF) remains uncertain. The authors
      present a case presenting with anterior fossa dural AVF, which developed after
      the resection of cerebellar arteriovenous malformation (AVM). The anterior fossa
      dural AVF, which was not observed on the preoperative angiography, was diagnosed
      on the follow-up angiography, after the resection of cerebellar AVM. A mechanism
      underlying the present case is not clearly understood. To the best of our
      knowledge, some cases of dural AVF secondary to craniotomy have been reported. It
      is postulated that intracranial vascular anomaly should be analyzed after the
      surgery.

PMID- 16277225
TI  - [An adult case of precursor B cell lymphoblastic lymphoma extending from right
      neck to upper cervical spinal region].
AB  - We report the rare adult case of upper cervical spinal tumor diagnosed precursor
      B cell lymphoblastic lymphoma. A 48- year-old male had suffered from right neck
      pain and swelling for two months. He had no neurological symptoms. The serum
      level of IL-2 receptor was high (1,820 U/ml). The radiological examinations
      including MRI showed the tumor extending from right neck to the epidural space
      from medulla to the C4 level. The pathological diagnosis of biopsy specimens was
      malignant lymphoma. Since the early pre-B lymphoblast antigens were positive by
      the flow cytometry, the diagnosis was precursor B cell lymphoblastic lymphoma.
      This type of lymphoma is highly aggressive. The intensive chemotherapy regimen
      such as hyper-CVAD was superior to the lymphoma-like regimens. In the case showed
      the progressive neurological symptoms such as myelopathy and urinary
      incontinence, the immediate surgical decompression of the spinal cord may be
      necessary. Measurement of IL-2 receptor and biopsy with flow cytometry were
      necessary to work out the treatment strategy of the spinal malignant lymphoma. In
      this case, the complete response (CR) of the tumor was achieved with hyper-CVAD
      regimen and radiation therapy.

PMID- 16277226
TI  - [Immunohistochemical study is helpful for the diagnosis of cerebellar clear cell
      ependymoma with atypical radiological findings--case report].
AB  - A 67-year-old male presented with a clear cell ependymoma with symptoms of ataxic
      gait and dizziness. Magnetic resonance imaging showed a ring enhanced and
      circumscribed mass lesion with some cysts in the left cerebellar hemisphere, and
      the vertebral artery angiogram showed the vascurality of the tumor fed by both
      the left posterior inferior cerebellar artery and the left superior cerebellar
      artery mainly. They demonstrated suspicious finding of metastatic tumor,
      glioblastoma, or cystic meningioma. Surgery via the left suboccipital approach
      revealed a whitish and solid tumor, which was demarcated from the cerebellar
      parenchyma and had no continuity with the 4th ventricle. Total resection of the
      tumor was successfully performed. The hematoxilyn-eosin staining of the surgical
      specimen was similar to hemangioblastoma or oligodendroglioma, however,
      immunohistochemical findings for glial fibrillary acidic protein, vimentin,
      epithelial membrane antigen, and factor VIII were compatible with clear cell
      ependymoma. The patient's postoperative course was uneventful, and his symptoms
      improved. Clear cell ependymoma is known as a variant of ependymoma, which is
      usually located at the foramen of Monro. We think that the immunohistochemical
      study is highly helpful for the diagnosis of the cerebellar tumor with atypical
      presentation such as our case.

PMID- 16277227
TI  - [Unilateral spondylolysis with spina bifida occulta of lumbar spine--case report
      and review of the literature].
AB  - Unilateral spondylolysis and midline defects in the posterior spinal elements
      attributable to spina bifida occulta (SBO) result in the unilateral floating of
      the vertebral arch. We report a patient with unilateral spondylolysis associated
      with SBO in the lumbar spine and review the literature. This 71-year-old male
      experienced severe left leg pain and lumbago that worsened upon walking.
      Radiographic studies revealed SBO and unilateral spondylolysis of L5. The dural
      sac and left L5 nerve root were compressed by the organization of tissues around
      the spondylolysis. As his symptoms failed to respond to conservative treatment,
      he underwent unilateral laminectomy without fusion. At operation, the left lamina
      of L5 was floating and unstable; the right lamina was stable. Medial facetectomy
      at L4/5 and excision of the left floating lamina of L5 were performed. For
      satisfactory decompression of the dural sac and left L5 nerve root, the
      cartilaginous fibrous tissue around the lysis was removed. His symptoms
      disappeared immediately after surgery. Although long-term follow-up is necessary,
      we suggest that unilateral microdecompression without fusion is a useful method
      to treat patients with unilateral spondylolysis with SBO.

PMID- 16277228
TI  - [What causes Abeta amyloidosis in the brain?].

PMID- 16277229
TI  - [Biomarker and imaging of Alzheimer's disease].

PMID- 16277231
TI  - [Abeta vaccination and treatment of Alzheimer's disease].

PMID- 16277230
TI  - [Presymptomatic diagnosis, prevention and therapy].

PMID- 16277232
TI  - [How to review English-written manuscripts submitted to peer-review journals].
AB  - Using some examples, the author describes how to review English-written
      manuscripts submitted to peer-review journals. One of the most important
      responsibilities for reviewers is to return the comments to the editor before
      deadline. Reviewers should not only criticize but also attempt to improve
      manuscripts. Participation in journal review may facilitate critical thoughts on
      their own manuscript writing.

PMID- 16277233
TI  - [Clinical study of cervical myeloradiculopathy with carpal tunnel syndrome,
      double crush syndrome].
AB  - The hypothesis, "double crush syndrome (DCS)", is that neural function could be
      impaired when single axons, having been compressed in one region, become
      especially susceptible to damage in another. We retrospectively review our
      surgical cases with both cervical lesion and carpal tunnel syndrome, i.e., DCS.
      From January 2001 to January 2005, we have treated 7 patients (Male-4, Female-3,
      average age-59.9 years old) under the diagnosis of DCS. Cervical lesions were
      cervical spondylosis in 4 and cervical narrow canal in 3 patients. Peripheral
      entrapment neuropathy was carpal tunnel syndrome in all 7 cases. Initial
      operation was performed for cervical lesion in 2, carpal tunnel syndrome in 2,
      and 3 cases were operated simultaneously. The improvement rate by Neurosurgical
      Cervical Spine Scale (NCSS) was average 65.8%. The average follow-up period was
      18.2 months. Good results can be obtained in 5 cases, and poor results in 2 cases
      who underwent initial operation under the diagnosis of single lesion. It is well
      known that a discrepancy between neurological manifestation and neuro-imaging
      sometimes occurs in cervical lesions, and then DCS should be considered as a
      possible pathogenetic mechanism.

PMID- 16277234
TI  - [Guillain-Barre syndrome associated Campylobacter jejuni serogroup Penner A
      showing antecedent fever and abdominal pain without diarrhea].
AB  - We reported a 28-year-old woman who had Guillain-Barre syndrome (GBS). Eight days
      after fever up and abdominal pain, she had weakness and dysesthesia of both hands
      and feet. Campylobacter jejuni (C. jejuni) was isolated from her stool culture
      without diarrhea. IgG anti-GM1 antibody was detected in her serum. Nerve
      conduction studies revealed a predominantly axonal neuropathy. After intravenous
      immunoglobulin therapy, her symptoms promptly improved. Penner 19 of C. jejuni
      was isolated more frequently from the GBS patients than from sporadic enteritis
      patients. In this case, C. jejuni with the serogroup Penner A was isolated. The
      serogroup is detected rarely in GBS.

PMID- 16277235
TI  - [Pure akinesia presenting with antecollis].
AB  - We reported a 77-year-old woman having pure akinesia who presented with
      antecollis induced by L-threo-3, 4-dihydroxyphenylserine (L-DOPS). At the age of
      70, she noticed increasing difficulty in standing up from a seat and moving.
      Afterward, she developed gait disturbance with difficulty in initiating walking,
      frozen gait, and postural instability. At 73 years of age, she came to our
      hospital, because she gradually fell down easily. Neurological examination
      disclosed mild akinesia with freezing symptom and kinesie paradoxale. No evidence
      of dementia, supranuclear gaze palsy, pseudobulbar palsy, rigidity, or tremor
      were present. As she developed akinesia, of which L-dopa therapy achieved little
      improvement, we clinically diagnosed as having pure akinesia. At age 74, L-DOPS
      was administered at a dose of 300mg per day and gradually increased up to 900mg
      per day, because her postural reflex was markedly disturbed and gait showed
      severe unsteadiness. Amelioration of frozen gait and unsteadiness were
      recognized, but efficacy of L-DOPS was temporal. It is well known that reported
      cases of pure akinesia were pathologically diagnosed as having progressive
      supranuclear palsy (PSP) or pallido-nigro-luysian atrophy. Therefore, the present
      case was suspected as having pathological changes which involved degeneration of
      the substantia nigra and globus pallidus. After three years of treatment with L
      DOPS, at age 77, she was admitted to our hospital for abrupt onset of her dropped
      head. Hematological examinations were normal, cervical MRI showed no evidence of
      paracervical muscular atrophy, and electromyography did not demonstrate any
      abnormal change. In addition, her posterior cervical muscles showed abnormally
      high tension, so the dropped head was considered due to antecollis. After
      admission, antecollis disappeared rapidly following discontinuation of L-DOPS.
      However the mechanism of drug induced dystonia is imperfectly understood on the
      basis of the clinical course, L-DOPS was considered as possible cause of her
      antecollis. L-DOPS, artificial precursor of noradrenarine (NA), is thought to
      increase not only NA level in the CNS, but also inhibit release of acetylcholine.
      It is suggested that the antecollis of present case results from impairment of a
      normal dopaminergic-noradorenergic balance caused by increased NA and striatal
      dopamine deficiency. This is the first case of antecollis induced by L-DOPS in a
      pure akinesia patient, providing important information on mechanism of drug
      induced dystonia and indicating caution in the clinical use of L-DOPS.

PMID- 16277236
TI  - [Bilateral ptosis and upper gaze palsy with pupil sparing caused by midbrain
      hemorrhage].
AB  - The arrangement within the midbrain oculomotor nerve complex and crossed
      innervation of the superior rectus muscle are not elucidated in humans. A 65-year
      old woman visited our hospital complaining of difficulty opening her eyes.
      Neurological examination revealed bilateral ptosis and impaired supraduction. The
      pupils prompty constricted to light. Results of CT and MRI demonstrated that
      there was a hematoma located in the dorsal midbrain tegmentum that spared the
      rostral mid-brain. It was presumed that the nerves of the superior rectus and
      levator palpebrae lie in the midbrain tegmentum more dorsally and medially than
      the others. Furthermore, crossed innervation of the superior rectus muscle can
      explain that lesions located in the dorsal midbrain tegmentum cause more often
      impaired supraduction.

PMID- 16277237
TI  - [MR-digital subtraction angiography in the diagnosis of cerebral arteriovenous
      malformations].

PMID- 16277238
TI  - [A 73-year-old woman with depression, dementia, and parkinsonism].
AB  - We report a 73-year-old woman who had depression, dementia, and parkinsonism. She
      had postural tremor since her fortics. She was losing her weight since age 66
      years. She noted difficulty in walk at age 72 (2001). She could not stand without
      assistance on July 2001, and she became hypobulic. On admission to our hospital
      on November 2001, she had dementia and revised Hasegawa dementia scale (HDS-R)
      was 8/30. She had mild limitation of the upward gaze, and rigidity in the neck,
      but not in the limbs. Postural tremor was seen. No muscle weakness was noted and
      tendon reflexes were normal. She was treated with levodopa/carvidopa, but she did
      not improve. She did not eat much. She was transferred to another hospital and
      she suddenly died on January 2002. The patient was discussed in a neurological
      CPC, and a chief discussant arrived at a conclusion that the patient had
      Parkinson disease with dementia. Some participants thought the diagnosis was
      progressive supranuclear palsy or diffuse Lewy body disease. The examination at
      autopsy revealed mild neuronal loss and Lewy bodies in the substantia nigra. Many
      Lewy bodies were observed in the cerebral cortex which corresponded to the
      neocortical type of DLB, and Lewy neurites were seen in the CA2 of the
      hippocampus by immunohistochemistry for alpha-synuclein. Spongy change was seen
      in the parahippocampus. Pathological diagnosis was diffuse Lewy body disease.

PMID- 16277239
TI  - [Mechanisms for establishment of vertebrate left-right asymmetry].

PMID- 16277240
TI  - [Mitotic chromosomes: the amazing structure for life].

PMID- 16277241
TI  - [Determination of commissural neuronal fate].

PMID- 16277243
TI  - [Microorganisms in deep biosphere and hydrothermal system: potential roles in the
      co-evolution of earth and life].

PMID- 16277242
TI  - [Multi-gene expression clone design for conditional expression at near
      physiological levels of multiple heterologous genes in living cells].

PMID- 16277244
TI  - [Activation mechanism of PPARgamma by its endogenous ligands].

PMID- 16277245
TI  - [Novel palmitoyl acyl-transferase family: synaptic function regulated by PSD-95
      palmitoylating enzymes].

PMID- 16277246
TI  - [Genome analysis of the model organism Dictyostelium discoideum].

PMID- 16277247
TI  - [Donor action program].
AB  - Recent advances of organ transplantation accelerated shortage of organs. Donor
      Action Program (DAP) was developed to establish a proper donation process in a
      hospital using total quality management methodology. It has been demonstrated
      effective in increasing donation and has been introduced in 23 countries. In
      Japan preliminary study demonstrated that (1) DAP could be implemented and was
      likely to increase donation in Japan, (2) Japanese healthcare staffs were likely
      to underestimate social needs and clinical results of transplantation and to be
      suspicious about brain death, (3) they had limited knowledge and experience in
      communicating with family members of the deceased, and their needs for education
      were not satisfied. In order to implement DAP in Japan, an organization which is
      responsible for data management and development for educational program should be
      considered with high priority.

PMID- 16277248
TI  - [Organ sharing network for organ transplantation from heart-beating deceased
      donors].
AB  - Organ sharing network is indispensable for ensuring the fair, smooth and rapid
      shipping transplant organs. In Japan, Kidney Transplant Network was founded in
      1995, and thereafter reformed to Organ Transplant Network following the
      legislation and enforcement of Organ Transplant Act. Under these circumstances,
      36 cases of the organ donation from heart-beating deceased donor have been
      realized, and consequently 27 cases of cardiac transplants, 22 cases of lung
      transplants, 28 cases of liver transplants and 20 cases of combined pancreas and
      kidney transplants were done as for March of 2005. Clinical outcomes of these
      transplantations can be compared favorably to those of the West countries. The
      number of death on the waiting list, however, amounted to 70 for cardiac
      transplant, 67 for lung transplant, 134 for liver transplant, which would be 2.5
      to 5 times as much as those who underwent transplantation. To make a breakthrough
      in issues on the organ shortage, the public enlightenment, the promotion of donor
      cards/seals, the amendment of Organ Transplant Act and related regulations and
      the insurance coverage of the cost of organ donation/transplantation are urgent
      challenges today.

PMID- 16277249
TI  - [Organs shortage in the United States].
AB  - Since the law pertaining to deceased transplantation was legalized in October
      1997 in Japan, 140 cases of deceased transplants have been performed through
      March 2005. Patients on waiting lists, however, are increasing every year.
      Meanwhile patients traveling abroad in desperations to require donors also
      increase. In the United States, over 25,000 transplantations are performed
      annually. The number of patients on waiting list exceeded 86,000 in 2003. Organ
      shortages are a serious problem, even in the United States. Expanded criteria
      donor(ECD) and Model for endstage liver disease (MELD) scoring systems were
      implemented to improve some problems in kidney and liver allocation systems,
      respectively in 2002. Utilization of donated organs for non-citizens is limited
      in the United States. Japan must independently increase deceased donor
      transplantations.

PMID- 16277250
TI  - [Ethical guidelines of the Japan Society for Transplantation].
AB  - The Ethics Committee of the Japan Society for Transplantation (JST) renewed its
      Ethical Guidelines for Organ Transplantation in 2003, and the major points are as
      follows; 1. The role of the Japan Network of Organ Transplantation was described.
      2. The following ethical principles and informed consent standards should be
      implemented for living donors and should be confirmed by third-party personnels
      who have no relation or interests with the donor and/or with the recipient and
      who can act as an advocate of the donor. * voluntary willingness to donate; *
      free from coercion; * medically and socialy suitable (20 years old or older); *
      fully informed of the risks and benefits as a donor and; * fully informed of the
      risk, benefits, and alternative treatment to the recipient. 3. Living donors
      should be limited to the relatives within the 6th degree and the third by
      marriage. 4. Living donation other than those relatives should be individually
      approved by the institutional ethics committee (IEC) and should be reviewed by
      the JST. 5. Donors between 16 and 19 years can be chosen as an exception if they
      are interviewed and judged to be psychosocially suitable as the donor by
      psychiatricians, and such a transplantation should be individually approved by
      IEC.

PMID- 16277251
TI  - [Psychiatric problems in organ transplants: examples on the renal transplants
      from living relatives in Japan].
AB  - There has been an increase of the renal transplants from living relatives, making
      over 80% of all renal transplants thus leaving under 17% of them from cadaveric.
      As for living donors, anxiety and fear of physical vulnerability, possible
      complications/disabilities, and death/dying, triggered by the hospitalization; a
      sense of guilt and/or self-blame, or seeking for rewards/compensation, triggered
      by the transplant; and introjection, probiosis, regression, often presented post
      transplant. Depression is one of the significant problems among donors after
      failed transplant, but also even after successful renal transplant. It is called
      "paradoxical depression". As for recipients, anxiety, guilt feeling, anger are
      very common psychological issues before the operation. There are number of young
      adults who present marked anger and short temper, aggression and acting-out
      behavior as their defense mechanisms.

PMID- 16277252
TI  - [Reforming organ transplant law: a legal memorandum].
AB  - Two bills to reform 'Act Concerning Organ Transplantation' are going to the Diet.
      Both bills aim to enable to carry out'child organ transplantation'. The Japanese
      Act requires valid written consent of the donor to procure an organ from the dead
      body. A child under the age of fifteen is thought to be unable to express his or
      her valid will. This paper discusses various points implied in this issue: opt-in
      of donor, equality of human being prescribed in Constitution of Japan, the
      autonomy of the dead, preferred donation to a relative. Tissue transplantation
      and organ transplantation among the living, which are not included in the Act,
      are also discussed.

PMID- 16277253
TI  - [The role of procurement coordinator in Japan].
AB  - The donor transplant coordinator system of our country started in about 1985.
      However, they were hospital dependent. The Japan organ transplant network (JOTNW)
      of independent establishments was established in 1995. As a result, The
      transplant coordinator divided into JOTNW and those who recommended the
      prefecture. However, the qualification of mediator is the same. Most of the donor
      in our country is non-heart beating kidney transplant donor. Therefore, the donor
      transplant coordinator in our country also has treated mainly the non-heart
      beating donor cases. However, the organ donation in the brain death became
      possible by enforcing the Organ Transplant Law in October, 1997. Then, it
      explains coordinator's role in the organ donation in the brain death of our
      country with a lot of restrictions compared with another country this time.

PMID- 16277254
TI  - [A role of recipient coordinators in Japan].
AB  - Transplantation in Japan, as well as the environment in which nurses work, has
      been slowly changed. Consequently, those nurses started working as recipient
      coordinators to meet the needs of patients, physicians and nurses who work at the
      patients' bedside. In the future, recipient coordinators can be a valuable asset
      to each transplant program because of their education, commitment to personalized
      care to recipients and their families. This article describes a variety of roles
      of recipient coordinators in Japan.

PMID- 16277255
TI  - [Immunological tolerance].
AB  - New immunosuppressive agents have significantly improved early survival after
      organ transplantation for patients with end-stage organ failure. However, a major
      problem in transplantation is continued to be graft rejection. Chronic allograft
      rejection threatens the long-term survival of organ transplant recipients.
      Therefore, induction of donor specific tolerance is very important for improving
      long-term survival after transplantation. The costimulatory pathways are crucial
      in regulating T cell activation and donor specific tolerance. The costimulatory
      pathways are potential therapeutic targets for inducing donor specific tolerance
      and improving long-term survival after transplantation.

PMID- 16277256
TI  - [Clinical views from the forefront of immunosuppressive drugs].
AB  - Recently, many immunosuppressants have been developed and some of them have
      already been introduced in clinical organ transplantation. With a new concept of
      immunoregulation, which focuses on prevention of rejection and over
      immunosuppression, the latest protocol has been conducted. Chimeric or humanized
      antibodies targeting the lymphocyte surface molecule such as CD19, 20, 25, 40,
      and 52 are administrated in the induction phase, and calcineurin inhibitors
      (cyclosporin and tacrolimus) are used as key drugs. For tapering the doses of
      them, the combined application of anti-metabolic agents of azathioprine,
      mizoribine, or mycophenolate mofetil (MMF) has been proved effective. Lymphocyte
      forming drugs induce unique immunoregulation, targeting at sphingosine 1
      phosphate (SlP) receptors. FTY720 is now in the procedure of clinical trial to
      compare with MMF. KRP203 is also a candidate for more specific SIP receptor
      agonist. In this issue, I reviewed the recent immunosuppressive strategy and
      focused on the advance of novel immunosuppressive drugs.

PMID- 16277257
TI  - [HLA typing and transplantation].
AB  - Clinical trial of organ transplantation was renal transplantation by Voronoy at
      1936. The discovery of HLA in the 1950s was one of the most important new
      findings in the area of transplantation. Nowadays, developing HLA genotyping
      methods, the serum analysis does not use for donor and recipient HLA typing but
      for cross-matching test. Because each of HLA genotyping methods has its merits
      and demerits, it is important to choice right methods for avoiding type error.
      PCR-Luminex method using fluorescence microsphere was developed for high
      resolution HLA-A, HLA-B and HLA-DRB1 genotyping in the Japanese population. This
      genotyping method allows to define all the possible combinations of alleles at
      each loci existing in Japanese at the four-digital level. In hematopoietic stem
      cell transplantation, to match high resolution level of HLA between donor and
      recipient lead an improvement of recipient's survival. In organ transplantation,
      removed organ has to be so immediately transplanted into recipient that no time
      is left for HLA genotyping. In order to have good survival of transplanted organ,
      HLA, cytokine promoter lesion and immunoglobulin like receptor genotyping might
      be helpful. We focused on this review at HLA genotyping, especially new SSO
      methods.

PMID- 16277258
TI  - [Renal transplantation].
AB  - Recent immunosuppressive drugs, including mycophenolate mofetil and basiliximab
      in addition to calcineurin inhibitors, have reduced the incidence and severity of
      acute allograft rejection in kidney transplants. This article introduces newly
      developed agents such as CTLA4-Ig, LEA29Y, rituximab, and FTY720 and also reviews
      immunosuppressive protocols which withdraw steroid or calcineurin inhibitors.
      Unrelated or ABO incompatible living donor kidney transplants have increased due
      to advancement of immunosuppressive

PMID- 16277259
TI  - [Liver transplantation--present and future].
AB  - The outcome of liver transplantation for HBV-related liver disease has been
      dramatically improved by the introduction of hepatitis B immune globulin and
      antiviral drug such as lamivudine. On the other hand, prophylaxis against HCV
      recurrence has not been established. As for hepatocellular carcinoma, Milan
      criteria predict acceptable posttransplant outcome. MELD scores, calculated from
      serum creatinine, bilirubin, and PT-INR, have been shown to be effective in
      predicting patient survival 1) on the waiting list and 2) following
      transplantation. ABO-incompatible liver transplantation has been associated with
      poor patient survival, especially when the recipients are adults. Intraportal
      infusion of methylprednisolone, prostaglandin E1, and gabexate mesilate, however,
      has been reported to be effective. It has been reported that 12.4% of the living
      liver donor experienced postoperative complication, and therefore, more effort
      should be made to increase brain-dead donor.

PMID- 16277260
TI  - [Heart transplantation].
AB  - While nearly 4,000 patients undergo heart transplantation (HTx) every year in the
      world, only 27 HTx were performed since February, 1999, because of very strict
      Organ Transplantation Law in Japan. All were treated with triple
      immunosuppressive regimen. Although two patients died of infection 4 months and 4
      years after HTx, respectively, 23 were discharged and 16 returned to work or go
      to school. New immunosuppressive drugs, such as sirolimus and everolimus,
      treatment of presensitized patients before transplantation using cyclophosphamide
      and intravenous globulin infusion, compact implantable left ventricular assist
      supports and the future of pediatric HTx in Japan are discussed.

PMID- 16277261
TI  - [Clinical status of lung transplantation].
AB  - The first successful living-donor lobar lung transplant (LDLLT) in Japan was
      performed at Okayama University in October, 1998 after a long period of waiting
      for the legalization of the thoracic organ transplantation. By May, 2005, a
      further 67 lung transplants have been performed; 45 from living donors and 22
      from cadaveric donors. Although the number of lung transplants is still small,
      survival in Japan, at 76.9% after 5 years, is better than the world average.
      Because the number of available cadaveric donors for lung transplantation is
      limited at less than 5 per year, LDLLT is a realistic option for properly
      selected candidates.

PMID- 16277262
TI  - [Small bowel transplantation].
AB  - Early attempts of small bowel transplantation (SBTx) were unsuccessful as a
      result of uncontrolled rejection and infection. Introduction of tacrolimus in the
      early 1990s improved the outcome, but results were not satisfactory comparing
      those after the other organ transplants. Recently, improved long-term graft
      survivals were reported from several centers. According to Intestine Transplant
      Registry (ITR), a multivariate analysis of cases within the last 5 years revealed
      that transplantation of patients waiting at home, recipient age, antibody induced
      immune suppression, and center experience with at least 10 cases were associated
      with improved patients survival. One-year graft survival rate of 90% were
      achieved in patients who were treated with antithymocyte globulin and maintained
      on tacrolimus.

PMID- 16277263
TI  - [Current status of pancreas transplantation in Japan].
AB  - The pancreas transplantation is widely performed for the patients with type 1
      diabetes. To date in Japan we had 20 SPK or PAK transplants under the new brain
      death law launched in 1997. Despite severe shortage of organ donors and marginal
      donors such as old age, unstable homodynamic situation at agonal phase and
      atherosclerosis, all patients enjoy a post-operative life except two patients who
      had grafts removed due because of thrombosis and perforation. There are some
      reports recently presented at the meeting with respect to simultaneous pancreas
      kidney transplantations from living donors. It will be expected to have more
      donors and transplantation with satisfactory results in Japan as well.

PMID- 16277264
TI  - [Current status and perspective of pediatric liver transplantation in Japan].
AB  - In Japan, the annual number of pediatric liver transplantation (LT) has been
      stable around 140 in the last few years. Almost all of them are from living
      donors. Three fourth are indicated for cholestatic liver diseases, mainly biliary
      atresia. One year patient survival rate after pediatric LT in Japan is 85 %. In
      comparison to other indications, patient survival of the infants with fulminant
      hepatic failure is quite poor. Weaning protocol of immunosuppression in pediatric
      LT in Japan is going in many institutions, and has succeeded to obtain some
      number of recipients with complete tolerance. More attenuated immunosuppresion
      and intimate monitoring for EB virus infection using the real-time PCR has been
      effective to decrease the incidence of post-transplant lymphoproliferative
      disorder.

PMID- 16277265
TI  - [Pediatric kidney transplantation].
AB  - Recently we achieved good outcomes in pediatric renal transplantation under
      basiliximab induction steroid withdrawal regimen including ciclosporin and
      mycophenolate mofetil (1 and 2 years patient/graft survival rates; 100%/96.6%).
      Steroid was withdrawn in 3 children and was given alternatively in 18 among 30
      children under this regimen. Height standard deviation scores were significantly
      improved 1 year post-transplantation (-1.7+/-0.26 (mean+/-SE)), compared with
      those at transplantation (-2.1+/-0.23 (mean+/-SE)). Viral infection is still one
      of serious complications. Children tend to have symptomatic viral infection as a
      prime infection because of sero-negative antibodies against Cytomegalovirus (CMV)
      and Epstein-Barr virus(EBV). CMV was safely controlled with preemptive treatment
      monitoring with CMV antigenemia. EBV infection may result in posttransplant
      lymphoproliferative disease (PTLD). Ganciclovir for CMV and rituximab for EBV are
      useful. ABO blood group incompatible kidney transplantation demonstrated long
      term better outcomes in children than adult. Pneumococcal infection was
      unexpectedly rare despite of splenectomy. Preemptive transplantation should be
      recommended to avoid dialysis for children regarding of good outcomes. Cadaver
      donor transplantation for a small child resulted in poor outcomes. Therefore
      living donor kidney transplantation for a small child is preferred. Management of
      cardiovascular monitoring with Swan-Ganz catheter and transesophageal ultrasound
      is important to overcome size mismatch between small body and a large kidney. It
      improves cardiac output and keeps good recirculation in an adult renal allograft.
      Kidney transplantation for children with end stage renal disease should be
      considered earlier and preemptively to improve growth retardation and provide
      better quality of life.

PMID- 16277266
TI  - [Organ transplantation and pregnancy].
AB  - Organ transplantation in reproductive-age women increases in frequency each year.
      In the presence of stable graft function and stable maintenance immunosuppressive
      regimens, patients are more likely to have successful outcomes. It is reasonable
      to advise recipients to wait at least 2 years after transplant to become
      pregnant. Most pregnancies do not affect graft function significantly, while they
      are sometimes associated with obstetric complications such as spontaneous
      abortions, premature deliveries, low birth weight, intrauterine growth
      retardation, hypertension, infection, etc. in recipients. Immunosuppressive
      medications can be used safely during pregnancy, and they are necessary in order
      to prevent maternal and fetal complications secondary to graft rejection.
      Successful management of the pregnant recipients requires a multidisciplinary
      team.

PMID- 16277267
TI  - [Islet transplantation program in Japan].
AB  - In Japan, pancreas donation had been possible from cadaveric donors, either
      heartbeating or non-heart beating (NHB) donors. Pancreas allografts were
      distributed on organ allocation system of Japan Organ Transplant Network.
      Meanwhile, islet transplantation is categorized as tissue transplantation, and is
      free from legal restraints. Thus, pancreases for islet isolation should be
      obtained from NHB donors. Here, we report the starting program and preliminary
      results of islet transplantation in Japan. Selection and listing criteria for
      transplantation include regional priority, ABO blood type, previous islet
      transplant who can be insulin-independent, and a longer waiting time. Five
      institutes in Japan (Fukushima, Chiba, Kyoto, Kobe, and Fukuoka) are ready to
      start programs.

PMID- 16277268
TI  - [Treatment of recurred HCV infection after liver transplantation].
AB  - Prognosis of recurred HCV recipient after both deceased and live liver
      transplantation is quite worse in foreign countries, recently. The reason of this
      poor prognosis is believed as immune-suppressant, steroid bolus, aged donor and
      liver donor in USA and Europe. However, in Japan, survival ration of HCV
      recipients is 5% reduction than mean survival of live donor liver
      transplantation. In addition, post transplant treatment of recurred HCV recipient
      is not good result in out of Japan, because of high rate of withdraw or drop out
      with peg interferon and ribavirin. On the contrary, some of Japanese investigator
      reported with 40-50% SVR with same drug management. It is still controversy
      whether HCV recipients are poor prognosis after transplantation and treatment
      resistance.

PMID- 16277269
TI  - [Current status of therapeutic drug monitoring for immunosuppressive drugs].
AB  - Therapeutic drug monitoring(TDM) is advocate to provide information about the
      adequacy of a dosing regimen or likelihood of toxicity associated with drug. Such
      situations include large intra- and inter-individual variabilities in
      pharmacokinetics; correlation between drug concentrations and toxicity or between
      concentrations and efficacy; narrow therapeutic interval, meaning toxic symptoms
      close to concentration with full therapeutic effect; and absence of appropriate
      parameter to recognize pharmacological effect. Current clinical immunosuppressive
      regimens consist of combinations of drugs, to allow a reduction in the individual
      drug doses as a means widening the therapeutic interval and reduction the
      likelihood of individual drug toxicity. With the recent introduction of new
      immunosuppressive drugs, there is an unprecedented interest in TDM for
      immunosuppressive drugs. In this review I discuss the current status of
      pharmacokinetic monitoring for cyclosporine, tacrolimus and mycophenolate
      mofetil.

PMID- 16277270
TI  - [Pathological diagnosis of renal allograft rejection].
AB  - Renal allograft biopsy is essential to confirm the diagnosis of allograft
      rejection. International classification for allograft pathology (Banff scheme)
      greatly contributed to make a consensus of clinicopathological context of
      rejection. Two major pathogenesis of rejection are T-lymphocyte mediated and anti
      donor antibody-mediated rejection. Clinical and pathologic diagnostic criteria
      for antibody-mediated rejection have been well established during the last decade
      by Banff conference meeting report. Chronic rejection is definite entity from a
      view point of immunology, and chronic allograft failure is the most important
      cause of renal graft loss. Strategy to improve the long-outcome of renal
      allograft is required. However, pathologic diagnostic criteria of immunologic
      chronic rejection are not well established up to 1995. Recent advances in
      antibody-mediated rejection showed new insights to differentiate the pathogenesis
      of chronic rejection. Molecular pathology using DNA array analysis and other new
      technologies are expected to open new insights to the pathogenesis of renal
      allograft rejection.

PMID- 16277271
TI  - [The degradation of p27 and cancer].
AB  - The cell cycle of eukaryotic cells is regulated by a series of protein complexes
      composed of cyclins and cyclin-dependent kinases (CDKs), the activity of which is
      suppressed by a group of CDK inhibitors (CKIs). Among the CKIs, p27 plays a
      pivotal role in the control of cell proliferation. Degradation of p27 is a
      critical event for reentry of cells into the cell cycle from G0 phase and occurs
      through ubiquitination by two ubiquitin ligase complexes (KPC and SCFSkP2) and
      subsequent degradation by the 26S-proteasome. A tumor suppressing function of p27
      has been demonstrated in mouse models and studies of human tumors. This review
      will focus on the regulation of p27 proteolysis and its consequences for
      tumorigenesis.

PMID- 16277272
TI  - [Practical approaches to the osteoporosis treatment--instructions for drug use
      that draws the effect of the medicine].
AB  - Prophylaxis against bone fracture with osteoporosis therapy is of significant
      importance not only for preserving patients' activities of daily living (ADL) and
      quality of life(QOL), but also for saving and making effective use of social
      overhead capital. The author has treated patients with osteoporosis with
      risedronate, a bisphosphonate which has produced evidence of its clear efficacy
      in prophylaxis against bone fracture. The study has shown that the use of
      risedronate normalizes abnormal bone metabolism in a short time, which could not
      be corrected with active vitamin D3 preparations. Although bisphosphonates are
      effective in treatment of osteoporosis, a strict instruction to patients on the
      dosage often results in their inadequate compliance with the therapy. Thus, an
      instruction on the dosage more flexible about the timing of taking the drug was
      given, and then higher clinical benefit was obtained. By giving patients
      sufficient information on the importance of osteoporosis therapy and instructions
      on the dosage with a certain level of flexibility, osteoporosis therapy which
      brings out the greater potential of risedronate can be performed.

PMID- 16277273
TI  - Coding of color and form in the geniculostriate visual pathway (invited review).
AB  - We review how neurons in the principal pathway connecting the retina to the
      visual cortex represent information about the chromatic and spatial
      characteristics of the retinal image. Our examination focuses particularly on
      individual neurons: what are their visual properties, how might these properties
      arise, what do these properties tell us about visual signal transformations, and
      how might these properties be expressed in perception? Our discussion is inclined
      toward studies on old-world monkeys and where possible emphasizes quantitative
      work that has led to or illuminates models of visual signal processing.

PMID- 16277274
TI  - Visual neurophysiology: a field-effect amplifier designed and built by R. L. De
      Valois.
AB  - In the middle of the last century, R. L. De Valois designed and built a unique
      and effective amplifier based on the newly developed field-effect transistor
      (FET). This amplifier has many beneficial qualities for amplifying the signals of
      neurons with minimal disturbance. We have used this amplifier successfully for
      more than three decades. We describe the circuitry of the De Valois amplifier and
      provide performance specifications. The FET amplifier is one of De Valois's
      contributions to visual neurophysiology; we share the design in his honor, with
      the hope that it might prove useful to others.

PMID- 16277275
TI  - Contrast statistics for foveated visual systems: fixation selection by minimizing
      contrast entropy.
AB  - The human visual system combines a wide field of view with a high-resolution
      fovea and uses eye, head, and body movements to direct the fovea to potentially
      relevant locations in the visual scene. This strategy is sensible for a visual
      system with limited neural resources. However, for this strategy to be effective,
      the visual system needs sophisticated central mechanisms that efficiently exploit
      the varying spatial resolution of the retina. To gain insight into some of the
      design requirements of these central mechanisms, we have analyzed the effects of
      variable spatial resolution on local contrast in 300 calibrated natural images.
      Specifically, for each retinal eccentricity (which produces a certain effective
      level of blur), and for each value of local contrast observed at that
      eccentricity, we measured the probability distribution of the local contrast in
      the unblurred image. These conditional probability distributions can be regarded
      as posterior probability distributions for the "true" unblurred contrast, given
      an observed contrast at a given eccentricity. We find that these conditional
      probability distributions are adequately described by a few simple formulas. To
      explore how these statistics might be exploited by central perceptual mechanisms,
      we consider the task of selecting successive fixation points, where the goal on
      each fixation is to maximize total contrast information gained about the image
      (i.e., minimize total contrast uncertainty). We derive an entropy minimization
      algorithm and find that it performs optimally at reducing total contrast
      uncertainty and that it also works well at reducing the mean squared error
      between the original image and the image reconstructed from the multiple
      fixations. Our results show that measurements of local contrast alone could
      efficiently drive the scan paths of the eye when the goal is to gain as much
      information about the spatial structure of a scene as possible.

PMID- 16277276
TI  - Spatiochromatic statistics of natural scenes: first- and second-order information
      and their correlational structure.
AB  - Spatial filters that mimic receptive fields of visual cortex neurons provide an
      efficient representation of achromatic image structure, but the extension of this
      idea to chromatic information is at an early stage. Relatively few studies have
      looked at the statistical relationships between the modeled responses to natural
      scenes of the luminance (LUM), red-green (RG), and blue-yellow (BY)
      postreceptoral channels of the primate visual system. Here we consider the
      correlations among these channel responses in terms of pixel, first-order, and
      second-order information. First-order linear filtering was implemented by
      convolving the cosine-windowed images with oriented Gabor functions, whose gains
      were scaled to give equal amplitude response across spatial frequency to random
      fractal images. Second-order filtering was implemented via a filter-rectify
      filter cascade, with Gabor functions for both first- and second-stage filters.
      Both signed and unsigned filter responses were obtained across a range of filter
      parameters (spatial frequency, 2-64 cycles/image; orientation, 0-135 degrees).
      The filter responses to the LUM channel images were larger than those for either
      RG or BY channel images. Cross correlations between the first-order channel
      responses and between the first- and second-order channel responses were
      measured. Results showed that the unsigned correlations between first-order
      channel responses were higher than expected on the basis of previous studies and
      that first-order channel responses were highly correlated with LUM, but not with
      RG or BY, second-order responses. These findings imply that course-scale color
      information correlates well with course-scale changes of fine-scale texture.

PMID- 16277277
TI  - Stability of the color-opponent signals under changes of illuminant in natural
      scenes.
AB  - Illumination varies greatly both across parts of a natural scene and as a
      function of time, whereas the spectral reflectance function of surfaces remains
      more stable and is of much greater relevance when searching for specific targets.
      This study investigates the functional properties of postreceptoral opponent
      channel responses, in particular regarding their stability against spatial and
      temporal variation in illumination. We studied images of natural scenes obtained
      in UK and Uganda with digital cameras calibrated to produce estimated L-, M-, and
      S-cone responses of trichromatic primates (human) and birds (starling). For both
      primates and birds we calculated luminance and red-green opponent (RG) responses.
      We also calculated a primate blue-yellow-opponent (BY) response. The BY response
      varies with changes in illumination, both across time and across the image,
      rendering this factor less invariant. The RG response is much more stable than
      the BY response across such changes in illumination for primates, less so for
      birds. These differences between species are due to the greater separation of
      bird L and M cones in wavelength and the narrower bandwidth of the cone action
      spectra. This greater separation also produces a larger chromatic signal for a
      given change in spectral reflectance. Thus bird vision seems to suffer a greater
      degree of spatiotemporal "clutter" than primate vision, but also enhances
      differences between targets and background. Therefore, there may be a trade-off
      between the degree of chromatic clutter in a visual system versus the degree of
      chromatic difference between a target and its background. Primate and bird visual
      systems have found different solutions to this trade-off.

PMID- 16277278
TI  - Polymorphic New World monkeys with more than three M/L cone types.
AB  - Most New World (platyrrhine) monkeys have M/L cone photopigment polymorphisms
      that map directly into individual variations in visual sensitivity and color
      vision. We used electroretinogram flicker photometry to examine M/L cone
      photopigments in the New World monkey Callicebus moloch (the dusky Titi). Like
      other New World monkeys, this species has an M/L cone photopigment polymorphism
      that reflects the presence of X-chromosome opsin gene alleles. However, unlike
      other platyrrhines in which three M/L photopigments are typical, Callicebus has a
      total of five M/L cone photopigments. The peak sensitivity values for these
      pigments extend across the range from 530 to 562 nm. The result is an enhanced
      array of potential color vision phenotypes in this species.

PMID- 16277279
TI  - Classification images for chromatic signal detection.
AB  - The number and nature of the mechanisms for the detection of colored stimuli are
      still unclear. We use the paradigm of classification images to investigate the
      detection of a signal of homogeneous color added to a noisy texture. Both signal
      and noise colors were chosen from the isoluminant plane of the Derrington
      Krauskopf-Lennie (DKL) color space. The signal consisted of a square of
      homogeneous color that was chosen from either cardinal or noncardinal directions
      of the DKL color space. The noisy texture consisted of small squares of varying
      colors that were chosen randomly across the isoluminant plane. Classification
      images reveal that (1) the cardinal axes play no specific role; (2) the widths of
      the tuning curves vary between 30 and 90 deg, consistent with the variation of
      tuning widths of neurons at early cortical stages; and (3) detection is not based
      on the whole region covered by the signal but is influenced mostly by a small
      spot around the fixation point.

PMID- 16277281
TI  - Response saturation of monochromatic increments on intense achromatic
      backgrounds: implications for color-opponent organization in human vision.
AB  - We present evidence that steady achromatic adapting fields can produce response
      saturation in color-opponent pathways. We measured tvi (log increment threshold
      illuminance versus log background illuminance) functions at four test wavelengths
      (430, 490, 575, and 660 nm) and nine background illuminances from 4.0 to 5.6 log
      Td. Foveal, 2 degrees diameter, 1 s duration test stimuli were presented on a
      concentric, perceptually white (5128 degrees K color temperature), 7 degrees
      diameter, steady background. Thresholds were obtained by the method of
      adjustment, after which the test stimulus illuminances were increased 0.6 log
      unit and the subject estimated percentages of red, yellow, green, blue, and
      white. Average tvi slopes for two subjects were 2.06 for 430 nm, 1.6 for 490 nm,
      1.11 for 575 nm and 1.34 for 660 nm, consistent with the estimated ratios of
      chromatic to achromatic sensitivity at the same wavelengths. Also, the percentage
      of white seen in the suprathreshold increments increased with increasing
      background illuminance despite increases in excitation purity. These findings
      imply that steady, intense, achromatic backgrounds can produce response
      saturation in color-opponent mechanisms at wavelengths across the visible
      spectrum. The saturation was more extreme at short wavelengths than at middle or
      long wavelengths, producing a tritanopic condition at the highest background
      illuminances. The tritanopia reduced color space to a predominately red-blue
      dichromacy, in agreement with previous findings. The results support a multistage
      opponent-color model in which precortical koniocellular and parvocellular
      opponent pathways interact to produce the observed red-green and yellow-blue
      color-opponent channels at a cortical level.

PMID- 16277280
TI  - Do common mechanisms of adaptation mediate color discrimination and appearance?
      Uniform backgrounds.
AB  - Color vision is useful for detecting surface boundaries and identifying objects.
      Are the signals used to perform these two functions processed by common
      mechanisms, or has the visual system optimized its processing separately for each
      task? We measured the effect of mean chromaticity and luminance on color
      discriminability and on color appearance under well-matched stimulus conditions.
      In the discrimination experiments, a pedestal spot was presented in one interval
      and a pedestal + test in a second. Observers indicated which interval contained
      the test. In the appearance experiments, observers matched the appearance of test
      spots across a change in background. We analyzed the data using a variant of
      Fechner's proposal, that the rate of apparent stimulus change is proportional to
      visual sensitivity. We found that saturating visual response functions together
      with a model of adaptation that included multiplicative gain control and a
      subtractive term accounted for data from both tasks. This result suggests that
      effects of the contexts we studied on color appearance and discriminability are
      controlled by the same underlying mechanism.

PMID- 16277282
TI  - Bezold-Brucke effect in normal trichromats and protanopes.
AB  - Luminance-dependent change in color appearance--the Bezold-Brucke effect--was
      investigated in protanopes and related to that in normal trichromats. Spectral
      lights were presented at six luminance levels covering mesopic, low, and high
      photopic vision-across three log steps from 0.76 to 760 Td. To judge color
      appearance, a variant of the color-naming method was used with four primary basic
      color terms and a "White" response. This modification enabled us to examine
      apparent saturation changes along with the Bezold-Brucke hue shift. Color-naming
      frequency functions were acquired across ten presentations of each stimulus.
      Since protanopes name colors idiosyncratically, changes in color appearance
      cannot be quantified directly from the color-naming functions. To circumvent the
      difficulty, these functions were transformed into color similarity measures for
      analysis with multidimensional scaling purported to reconstruct individual color
      spaces. In these, luminance-dependent shifts in color appearance were represented
      by means of geometric displacements. We found that for normal trichromats, shifts
      measured in this way agreed with those derived in our study directly, and with
      the hue shifts reported in earlier studies. For protanopes, contrary to some
      models of dichromatic vision, changes in color appearance are significant and
      indicate superimposed shifts in hue and saturation. The results obtained for
      normal trichromats, especially for protanopes, imply that nonlinearity in the
      yellow-blue opponent system is insufficient to explain the Bezold-Brucke effect,
      given the nature of the saturation shift and the demonstrated divergence between
      unique hues and invariant hues.

PMID- 16277283
TI  - Effect of stimulus intensity on the sizes of chromatic perceptive fields.
AB  - The effects of intensity on chromatic perceptive field size were investigated
      along the horizontal meridian at 10 degrees temporal eccentricity by manipulating
      stimulus intensity from 0.3 to 3.3 log trolands. Following light adaptation,
      observers described the hue and saturation of monochromatic stimuli (440-660 nm,
      in 10 nm steps) for a series of test sizes (0.098-3 degrees) presented along the
      time period associated with the cone plateau of the dark-adaptation function.
      Perceptive field sizes of the four elemental hues (red, green, yellow, and blue)
      and the saturation component were estimated by three observers at each intensity
      level for each wavelength. In general, perceptive field sizes of blue and red are
      the smallest, and yellow and green are the largest. Furthermore, perceptive field
      sizes of all four hues decrease with increasing stimulus intensity, though the
      absolute change is largest for green and yellow. The decrease in size with
      increase in intensity cannot be completely explained in terms of saturation or
      rod signals and is likely, then, attributable to a cone-based mechanism.

PMID- 16277284
TI  - Seeing unique hues.
AB  - Hue can be described by four separate sensations of red (R), green (G), yellow
      (Y), and blue (B). These are combined in the spectrally opponent RG and YB
      mechanisms, whose null points correspond to the unique sensations of Y, G, B.
      Participants used a form of magnitude estimation to describe color appearance of
      light flashes that were systematically varied in size, luminance, duration,
      purity, and retinal eccentricity. Wavelengths of the unique hues were derived
      from the hue and saturation scaling functions. Only unique Y remained invariant
      across all the viewing conditions. The shifts in unique hues with test conditions
      place strong restrictions on models of how the RG and YB mechanisms are
      assembled. Despite polymorphism of L and M cones and variation of their ratios
      across participants and across the retina, the frequency distribution of unique Y
      was very narrow, implying some reweighting of cone inputs to individuals' RG
      mechanisms.

PMID- 16277285
TI  - Variations in normal color vision. IV. Binary hues and hue scaling.
AB  - We used hue cancellation and focal naming to compare individual differences in
      stimuli selected for unique hues (e.g., pure blue or green) and binary hues
      (e.g., blue-green). Standard models assume that binary hues depend on the
      component responses of red-green and blue-yellow processes. However, variance was
      comparable for unique and binary hues, and settings across categories showed
      little correlation. Thus, the choices for the binary mixtures are poorly
      predicted by the unique hue settings. Hue scaling was used to compare individual
      differences both within and between categories. Ratings for distant stimuli were
      again independent, while neighboring stimuli covaried and revealed clusters near
      the poles of the LvsM and SvsLM cardinal axes. While individual differences were
      large, mean focal choices for red, blue-green, yellow-green, and (to a lesser
      extent) purple fall near the cardinal axes, such that the cardinal axes roughly
      delineate the boundaries for blue vs. green and yellow vs. green categories. This
      suggests a weak tie between the cone-opponent axes and the structure of color
      appearance.

PMID- 16277286
TI  - Integration of differing chromaticities in early and midlevel spatial vision.
AB  - Using Glass patterns composed of isoluminant dots we have investigated the
      segregation and integration of chromatic information by the visual system. By
      measuring pattern detection when the chromaticities of the two elements forming a
      dot pair are varied (intradipole variation), we characterize integration at an
      early level of spatial processing. By measuring pattern detection for dot pairs
      where the within-pair chromaticity is the same but the among-pair chromaticities
      are varied (interdipole variation) we characterize integration and segregation
      for a more global, midlevel, spatial processing mechanism. Using isoluminant
      patterns in which all dots have the same chromaticity, we find that (i) detection
      thresholds are similar to those for luminance-defined dots, and (ii) an
      equivalent-contrast metric approximately equates thresholds for various
      chromaticities, including those along both the cardinal and the intermediate axes
      of an opponent-color space. When intradipole chromaticity is varied we observe
      that (i) the ability of visual mechanisms to extract oriented dot pairs decreases
      with increasing chromaticity differences, and (ii) average bandwidths are similar
      for cardinal and intermediate directions. For pattern detection with interdipole
      chromatic variation the visual system does not segregate noise dot pairs from
      correlated dot pairs on the basis of chromatic differences alone, and appears to
      integrate oriented dot pairs of differing chromaticities in forming a global
      percept, even for large color differences. Isoluminant Glass patterns with
      translational and concentric correlations give similar results. The results are
      compared with those obtained for contrast variation in luminance-defined Glass
      Patterns and are discussed in terms of current multistage models of color
      processing by the visual system.

PMID- 16277287
TI  - Induction effects for heterochromatic brightness matching, heterochromatic
      flicker photometry, and minimally distinct border: implications for the neural
      mechanisms underlying induction.
AB  - Brightness induction refers to the finding that the apparent brightness of a
      stimulus changes when surrounded by a black versus a white stimulus. In the
      current study, we investigated the effects of black/white surrounding stimuli on
      settings made between red and green stimuli on three different tasks:
      heterochromatic brightness matching (HBM), heterochromatic flicker photometry
      (HFP), and minimally distinct border (MDB). For HBM, subjects varied the relative
      luminance between the red and green stimuli so that the brightness of the two
      colors appeared equal. For the two other tasks, matches were made based on
      minimizing red/green flicker (HFP) or the saliency of a red/green border (MDB).
      For all three tasks, the presence of black/white surrounding stimuli
      significantly altered red/green settings, demonstrating the existence of
      induction effects. These results are discussed in terms of which underlying color
      pathways (L+ M versus L-M) may contribute to induction effects for the different
      tasks.

PMID- 16277288
TI  - Regulation of chromatic induction by neighboring images.
AB  - We deal with the regulation of chromatic contrast when the induction of a second
      stimulus (one of five neighboring surrounds) opposes the induction from a first
      stimulus (one of two remote vivid peripheral fields). Using a hue cancellation
      judgment, we show that, although every neighboring surround that we used has the
      same average chromatic content, the resulting color appearance of the target
      differs between surrounds, and this may be ascribed to the spatiochromatic
      organization of the surround. So, rather than the chromatic contrast amplitude or
      the frequential structure of the surround, it is the structure of proximity that
      matters.

PMID- 16277289
TI  - The watercolor illusion and neon color spreading: a unified analysis of new cases
      and neural mechanisms.
AB  - Coloration and figural properties of neon color spreading and the watercolor
      illusion are studied using phenomenal and psychophysical observations. Coloration
      properties of both effects can be reduced to a common limiting condition, a
      nearby color transition called the two-dot limiting case, which clarifies their
      perceptual similarities and dissimilarities. The results are explained by the
      FACADE neural model of biological vision. The model proposes how local properties
      of color transitions activate spatial competition among nearby perceptual
      boundaries, with boundaries of lower-contrast edges weakened by competition more
      than boundaries of higher-contrast edges. This asymmetry induces spreading of
      more color across these boundaries than conversely. The model also predicts how
      depth and figure-ground effects are generated in these illusions.

PMID- 16277290
TI  - Border-ownership-dependent tilt aftereffect.
AB  - Single-cell recordings from macaque visual cortex have shown orientation
      selective neurons in area in V2 code for border ownership [J. Neurosci. 20, 6594
      (2000)]: Each piece of contrast border is represented by two pools of neurons
      whose relative firing rate indicates the side of border ownership. Here we show
      that the human visual cortex uses a similar coding scheme by demonstrating a
      border-ownership-contingent tilt aftereffect. The aftereffect was specific for
      the adapted location, indicating that the adapted neurons have small receptive
      fields. We conclude that figure-ground organization is represented by border
      ownership-selective neurons at early stages in the human visual cortex.

PMID- 16277292
TI  - Spatial frequency tuning of brightness polarity identification.
AB  - Recent studies have shown that cells in the primary visual cortex can, in
      addition to borders, also encode surface brightness. Whether the brightness is
      encoded by a large extraclassical receptive field or by a filling-in type
      mechanism activated by the luminance border is not known. These explanations
      imply different spatial frequency tunings for the underlying mechanism. In a
      psychophysical masking paradigm we measured spatial frequency tuning functions
      for identification of both luminance polarity (bright/dark) and luminance border
      orientation of oval and circular luminance patches with variable diameters (0.2
      10 deg). For both tasks we obtained nearly overlapping narrow (1.5 octave)
      bandpass masking tuning functions centered at 1.5-5.0 c/deg. Stimulus size and
      shape had only minimal effect on the tuning functions. The results favor the idea
      of brightness filling-in and suggest that the cells activated by the luminance
      border modulate the activity of the cells signaling surface brightness. Further,
      the brightness processing mechanism is spatial frequency selective.

PMID- 16277293
TI  - Method of unconfounding orientation and direction tunings in neuronal response to
      moving bars and gratings.
AB  - When an oriented bar or grating is drifted across the receptive field of a
      cortical neuron at various orientations, the tuning function reflects both, and
      thus confounds the orientation (ORI) and the direction-of-motion (DIR)
      selectivity of the cell. Since ORI (or DIR), by definition, has a period of
      180(or 360) deg/cycle, a popular method for separating these two components, due
      to Worgotter and Eysel [Biol. Cybern. 57, 349 (1987)], is to Fourier decompose
      the neuron's response along the angular direction and then identify the first and
      the second harmonic with DIR and ORI, respectively (the SDO method). Zhang [Biol.
      Cybern. 63, 135 (1990)] pointed out that this interpretation is misconceived--all
      odd harmonics (not just the first harmonic) reflect the DIR component, whereas
      all even harmonics (including the second harmonic) contain contributions from
      both DIR and ORI. Here, a simplified procedure is proposed to accomplish the goal
      of unconfounding ORI and DIR. We first construct the sum of all odd harmonics of
      the overall tuning curve, denoted ODDSUM, by calculating the difference in the
      neuronal response to opposite drifting directions. Then we construct
      ODDSUM+/ODDSUM/ and identify it with DIR (here . denotes the absolute value).
      Subtracting DIR, that is ODDSUM+ /ODDSUM/, from the overall tuning curve gives
      ORI. Our method ensures that (i) the reconstructed DIR contains only one,
      positive peak at the preferred direction and can have power in all harmonics, and
      (ii) the reconstructed ORI has two peaks separated by 180 degrees and has zero
      power for all odd harmonics. Using this procedure, we have unconfounded
      orientation and direction components for a considerable sample of macaque striate
      cortical cells, and compared the results with those obtained using Worgotter and
      Eysel's SDO method. We found that whereas the estimate of the peak angle of ORI
      remains largely unaffected, Worgotter and Eysel's method considerably
      overestimated the relative strength of ORI. To conclude, a simple method is
      provided for appropriately separating the orientation and directional tuning in a
      neuron's response that is confounded as a result of the use of drifting oriented
      stimuli.

PMID- 16277291
TI  - Contextual effects in fine spatial discriminations.
AB  - The context in which a pattern is viewed can greatly affect its apparent
      contrast, a phenomenon commonly attributed to pooled contrast gain control
      processes. A low-contrast surround may slightly enhance apparent contrast,
      whereas increasing the contrast of the surround leads to a monotonic decline in
      contrast appearance. We ask here how the presence of a patterned surround affects
      the ability to perform fine, suprathreshold orientation, contrast, and spatial
      frequency discriminations as a function of surround contrast and phase. Our
      results revealed an unexpected dip in performance when center and surround were
      in phase and similar in contrast. These results suggest that additional
      processes, perhaps those involved in scene segregation, play a role in contextual
      effects on discrimination.

PMID- 16277294
TI  - Frequency and phase contributions to the detection of temporal luminance
      modulation.
AB  - Observers detected a temporally modulated luminance pattern embedded in dynamic
      noise. A Gabor function with a carrier frequency, in separate conditions of 0,
      1.56, or 3.12 Hz, modulated signal contrast. Classification images were
      constructed in the time, temporal frequency, and temporal phase domains. As
      stimulus frequency increased, amplitudes of the phase images decreased and
      amplitudes of the frequency images increased, indicating a corresponding shift in
      the observers' criteria. The reduced use of phase attenuated time-domain images
      from signal-absent trials, but physical interactions between signal and noise
      components tended to preserve time-domain images from signal-present trials. The
      results illustrate a frequency-dependent strategy shift in detection that may
      reflect a degree of stimulus uncertainty in the time domain.

PMID- 16277295
TI  - Psychophysical estimation of speed discrimination. I. Methodology.
AB  - Thresholds were assessed for a speed discrimination task with a pair of luminance
      defined drifting gratings. The design and results of a series of experiments
      dealing in general with speed discrimination are described. Results show that for
      a speed discrimination task using drifting gratings, simultaneous presentation of
      the pair of gratings (spatially separated) was preferred over sequential
      presentation (temporally separated) in order to minimize the effects of eye
      movements and tracking. An interstimulus interval of at least 1000 ms was
      necessary to prevent motion aftereffects on subsequently viewed stimuli. For the
      two reference speeds tested of 2 and 8 deg/s using identical spatial frequency or
      randomizing spatial frequency for the pair of gratings did not affect speed
      discrimination thresholds. Implementing a staircase method of estimating
      thresholds was preferred over the method of constant stimuli or the method of
      limits. The results of these experiments were used to define the methodology for
      an investigation of aging and motion perception. These results will be of
      interest and use to psychophysicists designing and implementing speed
      discrimination paradigms.

PMID- 16277296
TI  - Psychophysical estimation of speed discrimination. II. Aging effects.
AB  - We studied the effects of aging on a speed discrimination task using a pair of
      first-order drifting luminance gratings. Two reference speeds of 2 and 8 deg/s
      were presented at stimulus durations of 500 ms and 1000 ms. The choice of
      stimulus parameters, etc., was determined in preliminary experiments and
      described in Part I. Thresholds were estimated using a two-alternative-forced
      choice staircase methodology. Data were collected from 16 younger subjects (mean
      age 24 years) and 17 older subjects (mean age 71 years). Results showed that
      thresholds for speed discrimination were higher for the older age group. This was
      especially true at stimulus duration of 500 ms for both slower and faster speeds.
      This could be attributed to differences in temporal integration of speed with
      age. Visual acuity and contrast sensitivity were not statistically observed to
      mediate age differences in the speed discrimination thresholds. Gender
      differences were observed in the older age group, with older women having higher
      thresholds.

PMID- 16277297
TI  - Visual adjustments to temporal blur.
AB  - After observers have adapted to an edge that is spatially blurred or sharpened, a
      focused edge appears too sharp or blurred, respectively. These adjustments to
      blur may play an important role in calibrating spatial sensitivity. We examined
      whether similar adjustments influence the perception of temporal edges, by
      measuring the appearance of a step change in the luminance of a uniform field
      after adapting to blurred or sharpened transitions. Stimuli were square-wave
      alternations (at 1 to 8 Hz) filtered by changing the slope of the amplitude
      spectrum. A two-alternative-forced-choice task was used to adjust the slope until
      it appeared as a step change, or until it matched the perceived transitions in a
      reference stimulus. Observers could accurately set the waveform to a square wave,
      but only at the slower alternation rates. However, these settings were strongly
      biased by prior adaptation to filtered stimuli, or when the stimuli were viewed
      within temporally filtered surrounds. Control experiments suggest that the latter
      induction effects result directly from the temporal blur and are not simply a
      consequence of brightness induction in the fields. These results suggest that
      adaptation and induction adjust visual coding so that images are focused not only
      in space but also in time.

PMID- 16277298
TI  - Sensory recoding via neural synchronization: integrating hue and luminance into
      chromatic brightness and saturation.
AB  - If neural spike trains carry information in the frequency and timing of the
      spikes, then neural interactions--such as oscillatory synchronization--that alter
      spike frequency and timing can alter the encoded information. Using coupled
      oscillator theory, we show that synchronization-based processing can be used to
      integrate sensory information, resulting in new second-order sensory percepts
      signaled by the compromise frequency of the coupled system. If the signals to be
      coupled are nonlinearly compressed, the coupled system behaves as if it signals
      the product or ratio of the uncoupled signals, e.g., chromatic brightness can be
      signaled by the compromise frequency of coupled neurons responding to hue and
      luminance, and chromatic saturation can be signaled by the coupled frequency of
      neurons responding to hue and brightness, with a power- (Stevens's) law scaling
      like that observed psychophysically. These emergent properties of coupled sensory
      systems are intriguing because multiplicative processing and power-law scaling
      are fundamental aspects of sensory processing.

PMID- 16277299
TI  - Synthesis of oxytocin analogues with replacement of sulfur by carbon gives potent
      antagonists with increased stability.
AB  - [Chemical reaction: See text] The neuropeptide oxytocin 1 controls mammary and
      uterine smooth muscle contraction. Atosiban 2, an oxytocin antagonist, is used
      for prevention of preterm labor and premature birth. However, the metabolic
      lifetimes of such peptide drugs are short because of in vivo degradation. Facile
      production of oxytocin analogues with varying ring sizes wherein sulfur is
      replaced by carbon (methylene or methine) could be achieved by standard solid
      phase peptide synthesis using olefin-bearing amino acids followed by on-resin
      ring-closing metathesis (RCM). These were tested for agonistic and antagonistic
      uteronic activity using myometrial strips taken from nonpregnant female rats.
      Peptide 8 showed agonistic activity in vitro (EC50= 1.4 x 10(3) +/- 4.4 x 10(2)
      nM) as compared to 1 (EC50= 7.0 +/- 2.1 nM). Atosiban analogues 17 (pA2= 7.8 +/-
      0.1) and 18 (pA2= 8.0 +/- 0.1) showed substantial activity compared to the parent
      oxytocin antagonist 2 (pA2= 9.9 +/- 0.3). Carba analogue 35 (pA2= 6.1 +/- 0.1)
      had an agonistic activity over 2 orders of magnitude less than its parent 3 (8.8
      +/- 0.5). A comparison of biological stabilities of 1,6-carba analogues of both
      an agonist 8 and antagonist 18 versus parent peptides 1 and 2 was conducted. The
      half-lives of peptides 8 and 18 in rat placental tissue were shown (Table 2) to
      be greatly improved versus their parents oxytocin 1 and atosiban 2, respectively.
      These results suggest that peptides 8 and 18 and analogues thereof may be
      important leads into the development of a long-lasting, commercially available
      therapeutic for initiation of parturition and treatment of preterm labor.

PMID- 16277300
TI  - Exploring the scope of the 29G12 antibody catalyzed 1,3-dipolar cycloaddition
      reaction.
AB  - [Chemical reaction: See text] 29G12 is a murine monoclonal antibody programmed to
      catalyze the regio- and enantioselective 1,3-dipolar cycloaddition reaction
      between 4-acetamidobenzonitrile N-oxide 1a and N,N-dimethylacrylamide 2a (Toker,
      J. D.; Wentworth, P., Jr.; Hu, Y.; Houk, K. N.; Janda, K. D. J. Am. Chem. Soc.
      2000, 122, 3244). Given the unique nature of 29G12 as a protein biocatalyst for
      this chemical reaction, we have investigated both the substrate specificity and
      mechanistic parameters of the 29G12-catalyzed process. These studies have shown
      that while 29G12 is specific for its dipole substrate 1a, the antibody is highly
      promiscuous with respect to the dipolarophiles it can process. 29G12 accepts a
      bulky hydrophobic dipolarophile cosubstrate, with rates of product formation up
      to 70-fold faster than with the original substrate 2a. In all cases, the
      respective isoxazoline products are produced with exquisite regio- and
      stereochemical control (78-98% ee). Comparison between the steady-state kinetic
      parameters from the 29G12-catalyzed reaction of 1a with the most efficient versus
      the original dipolarophile cosubstrate (2m and 2a, respectively), reveals that
      while the effective molarities (EM)s are almost identical (EM(2m)) 26 M; EM((2a))
      23 M), the affinity of 29G12 for the larger dipolarophile 2m is more than 1 order
      of magnitude higher than for 2a [Km(2m) 0.44 +/- 0.04 mM; Km(2a) 5.8 +/- 0.4 mM].
      Furthermore, when 2m is the cosubstrate, the affinity of 29G12 for its dipole 1a
      is also greatly improved [Km(1a) 0.82 +/- 0.1 mM compared to Km(1a) 3.4 +/- 0.4
      mM when 2a is the cosubstrate]. An analysis of the temperature dependence of the
      29G12-catalyzed reaction between 1a and 2m reveals that catalysis is achieved via
      a decrease in enthalpy of activation (DeltaDeltaH 4.4 kcal mol(-1)) and involves
      a large increase in the entropy of activation (DeltaDeltaS 10.4 eu). The improved
      affinity of 29G12 for the nitrile oxide 1a in the presence of 2m, coupled with
      the increase in DeltaDeltaS during the 29G12-catalyzed reaction between 1a and 2m
      supports the notion of a structural reorganization of the active site to
      facilitate this antibody-catalyzed reaction.

PMID- 16277301
TI  - A DFT theoretical study of the condensation of aggregates of sp2 organolithium
      compounds on formaldehyde.
AB  - [Chemical reaction: See text] The interaction between three different sp2
      organolithium compounds (vinyllithium, 2-methoxyvinyllithium and phenyllithium)
      and formaldehyde has been investigated using DFT theoretical methods. The
      unsolvated monomers and dimers have been considered and compared to the 1:1 mixed
      aggregates formed with lithium dimethylamide. In all cases, the separate
      entities, their docking complexes, the transition states, and the condensation
      products have been characterized and compared to the corresponding situations
      involving methyllithium, taken as a prototypic sp3 nucleophile. Regarding the
      monomers, this study shows that, in the three cases considered, formaldehyde
      forms a pretransition state complex in which the oxygen of the carbonyl interacts
      with the lithium cation along one of its lone pair. A small energy barrier (< or
      =2.1 kcal.mol(-1)) brings to the transition state, then to the lithium alcoholate
      resulting from the largely exothermic condensation (approximately 40 kcal.mol(
      1)). The structure of the homogeneous dimers considered in a second step has been
      optimized and lead to arrangements in which a planar quadrilateral C-Li-C-Li is
      always obtained. In the presence of formaldehyde, these entities provide
      complexes exhibiting lithium-oxygen interaction similar to those occurring with
      the monomers. For the dimers, the geometry at the TS evokes a pi-complex between
      the C=O and the lithium cation, particularly pronounced in the case of
      phenyllithium. The resulting alcoholates are obtained following a larger
      exothermic reaction (approximately 55 kcal.mol(-1)). The heterogeneous dimers
      with lithium dimethylamide have been finally examined. In these cases, the
      aldehyde can orientate toward either the carbon or the nitrogen, leading to the
      expected lithium alcoholate or alpha-amino alcoholate, respectively. Whatever the
      orientation, the complexes present characteristics close to those calculated for
      the homogeneous dimer complexes. These similarities are conserved at the
      transition state.

PMID- 16277302
TI  - Regio- and stereoselective synthesis of aminoinositols and 1,2-diaminoinositols
      from conduritol B epoxide.
AB  - [Chemical reaction: See text] A systematic approach to the regio- and
      stereoselective synthesis of aminoinositols and 1,2-diaminoinositols arising from
      tetra-O-benzylconduritol B epoxide (9) and its aziridine analogue 22,
      respectively, is described. In all cases, the synthetic methodologies rely on the
      regio- and stereocontrolled azidolysis of the starting precursors to give the
      corresponding trans regioadducts. Subsequent functional group manipulation under
      strict configurational control affords the isomeric cis adducts. Chemoselective
      functionalization of the diamine moiety in 1,2-diaminoinositol derivatives can be
      achieved by the proper design of the reaction sequence and choice of reagents.
      The described protocols allow efficient access to each of the eight possible
      configurations of the 1,2-diamino and 1,2-amino alcohol moieties from chemical
      modifications of the epoxide moiety on the common precursor 9.

PMID- 16277303
TI  - Formation of modified cytosine residues in the presence of depurinated DNA.
AB  - [Chemical reaction: See text] Depurination is an important degradation pathway
      for antisense phosphorothioate oligonucleotides under conditions of thermal
      stress. We present evidence showing that depurinated oligonucleotides react with
      cytosine-containing sequences giving products containing a 6-(2-deoxy-beta-D
      erythro-pentofuranosyl)-3-(2-oxopropyl)imidazo[1,2-c]pyrimidin-5(6H)-one residue.
      Further, we demonstrate that the same product is formed upon treatment of 2'
      deoxycytidine with 4-oxo-2-pentenal, the latter being an expected byproduct of
      serial elimination reactions at apurinic sites. In addition to being important
      for synthetic oligonucleotides, apurinic site formation in cellular DNA is a
      common occurrence. Because repair of these sites can result in the production of
      4-oxo-2-pentenal, it is interesting to speculate whether 6-(2-deoxy-beta-D
      erythro-pentofuranosyl)-3-(2-oxopropyl)imidazo[1,2-c]pyrimidin-5(6H)-one residues
      can form in vivo.

PMID- 16277304
TI  - Synthetic studies on stevastelins. 1. Total synthesis of stevastelins B and B3.
AB  - [Chemical reaction: See text] The synthesis of stevastelin B3 (2) and B (5) are
      described. In a first approach, epoxy cyclodepsipeptide 8 was considered as a
      promising candidate for the synthesis of the [15]-membered ring members of the
      stevastelins; however, the oxirane ring opening, required for the completion of
      the natural stevastelin synthesis, failed. Thus, we synthesized stevastelin B
      (5), carrying out the oxirane ring opening earlier in the synthesis and following
      a synthetic scheme capable of delivering analogues. On the other hand, a
      translactonization reaction of the [15]-membered ring derivative 59 led to the
      total synthesis of the natural [13]-membered ring component of the stevastelins
      family, stevastelin B3 (2).

PMID- 16277305
TI  - Synthetic studies on stevastelins. 2. Synthesis of lipidic- and peptidic-modified
      analogues.
AB  - [Chemical reaction: See text] The synthesis of a series of stevastelin analogues
      with modification of the susbstituent at the C-2 position of the stearic acid
      chain (compounds 28 and 31), variation of the amino acids (compounds 41, 42, 73,
      and 78), or lacking the lipidic chain (compound 91) is described. The replacement
      of L-valine and L-threonine with other amino acids proceeded without difficulties
      for the synthesis of analogues 41 and 42; however, the substitution of L-serine
      with simple amino acids, such as glycine or L-alanine, proved to be elusive,
      which was adscribed to factors of conformational flexibility. Finally, the
      substitution with L-valine or L-threonine proceeded without difficulties to
      provide the analogues 73 and 78 respectively.

PMID- 16277306
TI  - Benzotriazole-assisted thioacylation.
AB  - [Chemical reaction: See text] Benzotriazole reagents for thioacylation (RCSBt),
      thiocarbamoylation (RR'NCSBt), aryl/alkoxythioacylation (ROCSBt), and
      aryl/alkylthiothioacylation (RSCSBt) are synthesized, and their utility is
      assessed by syntheses of representative heteroaryl thioureas 3a-g, thioamides 15a
      s, thionoesters 16a-h, thiocarbamates 17a-e, dithiocarbamates 18a-d,
      thiocarbonates 19a-c, and dithiocarbonates 20a-c.

PMID- 16277307
TI  - Tetrahaloindate(III)-based ionic liquids in the coupling reaction of carbon
      dioxide and epoxides to generate cyclic carbonates: H-bonding and mechanistic
      studies.
AB  - The microwave reactions of InX3 with [Q]Y produce a series of
      tetrahaloindate(III)-based ionic liquids (ILs) with a general formula of
      [Q][InX3Y] (Q = imidazolium, phosphonium, ammonium, and pyridinium; X = Cl, Br,
      I; Y = Cl, Br). The reaction of CO2 with a variety of epoxides has been examined
      in the presence of these ILs wherein tetrahaloindate(III)-based ILs are found to
      exhibit high catalytic activities and evidence is presented that supports the
      significant role of H-bonding interactions in the [Q][InX3Y]-catalyzed coupling
      reactions. The effects of various parameters such as temperature, pressure, and
      molar ratio of propylene oxide to catalyst have been investigated, and the
      plausible reaction mechanism based on the 1H and 13C NMR studies is presented for
      the formation of propylene carbonate.

PMID- 16277308
TI  - An enthalpic scale of hydrogen-bond basicity. 3. Ammonia, primary, secondary, and
      tertiary amines.
AB  - A reliable enthalpic scale of hydrogen-bond acceptor strength (basicity) is built
      for aliphatic amines by means of a new infrared method, from the temperature
      variation of hydrogen-bond equilibrium constants. Enthalpies of hydrogen bonding
      to a reference hydrogen-bond acceptor, 4-fluorophenol, have been determined in
      CCl4 and/or C2Cl4 for ammonia and 68 primary, secondary, and tertiary amines. The
      scale spans from -23.8 kJ mol(-1) for i-Pr2NCH(Et)2 to -39.4 kJ mol(-1) for Et3N.
      This large variation is mainly explained by the basicity-enhancing electronic
      effects of alkyl groups, which can be overcompensated by dramatic basicity
      decreasing steric effects. Relationships between DeltaH degrees and the change in
      electronic energy or the infrared shift of the OH stretching upon hydrogen
      bonding are studied and found useful in the prediction of the hydrogen bond
      enthalpies of amines with several hydrogen-bond acceptor sites. A careful
      statistical analysis of the enthalpy-entropy relationship shows an isoentropic
      tendency. The entropies of 65% of hydrogen-bonding reactions between aliphatic
      amines and 4-fluorophenol have a mean value of -55.1 +/- 4.2 J K(-1) mol(-1).
      Amines excluded from the isoentropic set are mainly severely hindered ones. The
      hydrogen-bond enthalpic scale can be useful in measuring the electrostatic
      character of Lewis bases.

PMID- 16277309
TI  - Synthesis of 2'-C-difluoromethylribonucleosides and their enzymatic incorporation
      into oligonucleotides.
AB  - [Chemical reaction: See text] Nucleosides bearing a branched ribose have
      significant promise as therapeutic agents and biotechnological and biochemical
      tools. Here we describe synthetic entry into a new subclass of these analogues,
      2'-C-beta-difluoromethylribonucleosides. We constructed the glycosylating agent 4
      in three steps from 1,3,5-tri-O-benzoyl-alpha-D-ribofuranose 1. The key steps
      included nucleophilic addition of difluoromethyl phenyl sulfone to 2-ketoribose 2
      followed by mild and efficient reductive desulfonation. Ribofuranose 4
      glycosylated bis(trimethylsilyl)uracil directly, giving difluoromethyluridine 7
      efficiently after deprotection. Conversion of 4 to the corresponding
      ribofuranosyl bromide allowed efficient access to C, A, and G analogues. A
      related approach starting from methyl D-ribofuranose offered synthetic entry into
      the diastereomeric manifold, 2'-C-alpha-difluoromethyl-arabino-alpha-pyrimidine.
      To incorporate 2'-C-beta-difluoromethyluridine into an oligodeoxynucleotide we
      converted 7 to the bisphosphate and carried out successive ligation reactions
      using T4 RNA ligase and T4 DNA ligase. Analogous to natural RNA linkages, the
      resulting oligonucleotide undergoes hydroxide-catalyzed backbone scission at the
      difluoromethyluridine residue via internal transphosphorylation.

PMID- 16277311
TI  - Oxygenation of alkane C-H bonds with methyl(trifluoromethyl)dioxirane: effect of
      the substituents and the solvent on the reaction rate.
AB  - [Chemical reaction: See text] The mechanism of the oxygenation of alkane C-H
      bonds with methyl(trifluoromethyl)dioxirane (1a) is studied through the effect of
      the substituent and solvent on the rate of oxygenation of 2-substituted
      adamantanes (2). The results suggest a remarkable electron deficiency at the
      reacting carbon atom in the transition state leading to the regular oxygenation
      products. The linearity of the Hammett plot reveals that the reaction mechanism
      does not change within a range of 0.15-0.67 units of sigma(I). A change in the
      solvent does not affect the distribution of the products, indicating a through
      bond transmission of the substituent effect as the origin of the deactivation of
      the substrate.

PMID- 16277310
TI  - Chiral synthesis of functionalized tetrahydropyridines: gamma-aminobutyric acid
      uptake inhibitor analogues.
AB  - [Chemical reaction: See text] A convenient preparation of functionalized chiral
      tetrahydropyridine-3-carboxylates from nitriles in 68-90% enantiomeric excess
      (ee) via allylboration, followed by a conjugate addition-elimination and ring
      closing metathesis, has been developed. Thus, the treatment of the acetate
      derived from vinylalumination of formaldehyde by use of [alpha
      (ethoxycarbonyl)vinyl]diisobutylaluminum with chiral beta-substituted and beta
      unsubstituted homoallylic amines, prepared in >98% diastereomeric excess (de) and
      68-90% ee via allylboration of the corresponding N-aluminoimines, furnished
      functionalized aminodienes, which underwent ring-closing metathesis to provide
      chiral C5-C6 disubstituted tetrahydropyridine-3-carboxylates. This methodology
      has been applied for the synthesis of a chiral C6-substituted tetrahydropyridine
      with known GABA-inhibiting properties at low concentrations.

PMID- 16277313
TI  - Synthesis, structure, and computational studies of soluble conjugated
      multidentate macrocycles.
AB  - [Chemical reaction: See text] Conjugated, shape-persistent macrocycles based on
      [3 + 3] Schiff-base condensation are of interest for supramolecular materials. In
      an effort to develop new discotic liquid crystals based on these compounds, a
      series of macrocycles with peripheral alkoxy groups of varying length have been
      prepared. The synthesis and mechanism of formation have been probed by isolation
      of oligomeric intermediates. A single-crystal X-ray diffraction study of one
      macrocycle revealed a nonplanar, strongly hydrogen-bonded structure. To our
      surprise, even with very long substituents, the macrocycles were not liquid
      crystalline. This has been rationalized by ab initio calculations that indicate
      the macrocycles are undergoing rotation of the dihydroxydiiminobenzene rings that
      may not allow a stable discotic liquid crystalline phase. These results provide
      new insight into the formation and properties of these large macrocycles and may
      provide guidance to developing stable liquid crystalline materials in the future.

PMID- 16277312
TI  - Synthesis and properties of nucleic acid analogues consisting of a benzene
      phosphate backbone.
AB  - [Chemical reaction: See text] The synthesis and properties of a nucleic acid
      analogue consisting of a benzene-phosphate backbone are described. The building
      blocks of the nucleic acid analogue are composed of bis(hydroxymethyl)benzene
      residues connected to nucleobases via the biaryl-like axis. Stabilities of the
      duplexes were studied by thermal denaturation. It was found that the thermal
      stabilities of the duplexes composed of the benzene-phosphate backbone are highly
      dependent on their sequences. The duplexes with the benzene-phosphate backbone
      comprised of the mixed sequences were thermally less stable than the natural DNA
      duplexes, whereas that composed of the homopyrimidine and homopurine sequences
      was thermally and thermodynamically more stable than the corresponding natural
      DNA duplex. It was suggested that the analogues more efficiently stabilize the
      duplexes in a B-form duplex rather than in an A-form duplex. Thus, the duplexes
      consisting of the benzene-phosphate backbone, especially composed of the
      homopyrimidine and homopurine sequences, may offer a novel structural motif
      useful for developing novel materials applicable in the fields of bio- and
      nanotechnologies.

PMID- 16277314
TI  - Different behavior of nitrenes and carbenes on photolysis and thermolysis:
      formation of azirine, ylidic cumulene, and cyclic ketenimine and the
      rearrangement of 6-phenanthridylcarbene to 9-phenanthrylnitrene.
AB  - Flash vacuum thermolysis (FVT) of 9-azidophenanthrene 8, 6-(5
      tetrazolyl)phenanthridine 18, and [1,2,3]triazolo[1,5-f]phenanthridine 19 yields
      9-cyanofluorene 12 as the principal product and 4-cyanofluorene as a minor
      product. In all cases, when the product is condensed at or below 77 K, the seven
      membered ring ketenimine 24 is detectable by IR spectroscopy (1932 cm(-1)) up to
      200 K. Photolysis of Ar matrix isolated 8 at lambda = 308 or 313 nm generates at
      first the azirine 26, rapidly followed by the ylidic cumulene 27. The latter
      reverts to azirine 26 at lambda > 405 nm, and the azirine reverts to the ylidic
      cumulene at 313 nm. Nitrene 9 is observed by ESR spectroscopy following FVT of
      either azide 8, tetrazole 18, or triazole 19 with Ar matrix isolation of the
      products. Nitrene 9 and carbene 21 are observed by ESR spectroscopy in the Ar
      matrix photolyses of azide 8 and triazole 19, respectively.

PMID- 16277315
TI  - Nanoscale borromeates.
AB  - [Structure: See text] In addition to a parent zinc(II) Borromean ring (BR)
      complex, the preparation and characterization of two hexasubstituted BR complexes
      with either 4-acetoxymethylphenyl or 4-methylthiophenyl substituents associated
      in turn with all six pyridyl rings has been achieved convergently in good yields
      by appealing to the dynamic features of the reactions between primary amino
      groups in a preformed acyclic ligand and 2,6-diformylpyridine. Two molecules of
      the acyclic ligands react with two molecules of 2,6-diformylpyridine to form a
      cyclic [2 + 2] tetraimine in the presence of Zn(II) ions as templates in 2
      propanol at 70 degrees C. The successful preparation of the two derivatives by
      convergent template-directed syntheses opens up opportunities to self-assemble,
      under equilibrium control, numerous nanoscale metallo-organic particles with
      potentially useful properties.

PMID- 16277316
TI  - (+)- and (-)-2-aminocyclobutane-1-carboxylic acids and their incorporation into
      highly rigid beta-peptides: stereoselective synthesis and a structural study.
AB  - [Chemical reaction: See text] Several derivatives of (+)- and (-)-2
      aminocyclobutane-1-carboxylic acid, 1, have been prepared through
      enantiodivergent synthetic sequences. The stereoselective synthesis of free amino
      acid (+)-1 has been achieved, and this product has been fully characterized for
      the first time. Stereocontrolled alternative synthetic methodologies have been
      developed for the preparation of bis(cyclobutane) beta-dipeptides in high yields.
      Among them, enantio and diastereomers have been synthesized. beta,beta- and
      beta,delta-Dimers resulting from the coupling of a cyclobutane residue and a
      linear amino acid have also been prepared. The ability of the cyclobutane ring as
      a structure-promoting unit both in the monomers and in the dimers has been
      manifested. The NMR structural study and DFT theoretical calculations evidence
      the formation of strong intramolecular hydrogen bonds giving rise to cis-fused
      [4.2.0]octane structural units that confer high rigidity on these molecules both
      in solution and in the gas phase. The contribution of a cis-trans conformational
      equilibrium derived from the rotation around the carbamate N-C(O) bond has also
      been observed, the trans form being the major conformer. In the solid state, this
      equilibrium does not exist, and moreover, intermolecular hydrogen bonds are
      present.

PMID- 16277317
TI  - A compact all-carbon tripodal tether affords high coverage of porphyrins on
      silicon surfaces.
AB  - [Structure: See text] Redox-active molecules designed to give high charge density
      on electroactive surfaces are essential for applications in molecular information
      storage. To achieve a small molecular footprint and thereby high surface charge
      density, a compound consisting of a triallyl tripod attached via a p-phenylene
      unit to a porphyrin (1) has been synthesized. The zinc chelate of 1 (Zn-1) was
      attached to Si(100). Electrochemical measurements indicate that the molecular
      footprint (75 A) in the monolayer is only approximately 50% larger than the
      minimum achievable, indicating high surface coverage. IR spectroscopy indicates
      that the bands due to the nu(C=C) (1638 cm(-1)) and gamma(CH) (915 cm(-1))
      vibrations present in the solid sample (KBr pellet) are absent from the spectra
      of the monolayers of Zn-1, consistent with saturation of the double bond in each
      of the three legs of the tripod upon the hydrosilylation process accompanying
      attachment. Comparison of the relative intensities of the in-plane (998 cm(-1))
      versus out-of-plane (797 cm(-1)) porphyrin modes indicates the average tilt angle
      (alpha) of the porphyrin ring with respect to the surface normal is approximately
      46 degrees , a value also observed for analogous porphyrins tethered to Si(100)
      via monopodal carbon linkers. Accordingly, the higher packing densities afforded
      by the compact tripodal linker are not due to a more upright orientation on the
      surface. The charge-retention half-lives (t1/2) for the first oxidation state of
      the Zn-1 monolayers increase from 10 to 50 s at low surface coverage (1-5 x 10(
      11) mol.cm(-2)) to near 200 s at saturation coverage (approximately 2 x 10(-10)
      mol.cm(-2)). Taken together, the high surface charge density (despite the lack of
      upright orientation) of the triallyl-tripodal porphyrin makes this construct a
      viable candidate for molecular information storage applications.

PMID- 16277318
TI  - Synthesis, reaction, and recycle of fluorous palladium catalysts for an
      asymmetric allylic alkylation without using fluorous solvents.
AB  - [Chemical reaction: See text] Chiral fluorous aminophosphine 4c bearing two
      fluorous ponytails was prepared from (S)-prolinol and applied to palladium
      catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (7)
      with a dialkyl malonate-BSA-LiOAc system with high enantioselectivities (up to
      97% ee). Results indicated that the chiral fluorous palladium catalyst from
      ligand 4c was easily separated from the reaction mixture by simple solid/liquid
      separation and could be reused up to five times.

PMID- 16277319
TI  - Free-radical-5-exo-trig cyclization of chiral 3-silylhepta-1,6-dienes: concise
      approach to the A-B-C ring core of hexacyclinic acid.
AB  - [Chemical reaction: See text] Free-radical-mediated 5-exo-trig cyclization of
      hepta-1,6-dienes 6a-c incorporating an allylsilane moiety was shown to provide at
      low temperature exclusively the trans-cis cyclopentanes 7a-c in good yield. In
      contrast, the same reaction with the alkyl analogue 9a led to the formation of
      all four possible stereoisomers. Interestingly, extension of this sequence of
      radical processes to alkoxy analogues 12-14 provided the complementary cis-cis
      stereoisomers with modest to excellent stereoselectivity. It is noteworthy that
      under such conditions allylsilanes were found to be much more reactive than their
      alkyl and alkoxy analogues. Beckwith-Houk-type models were proposed that
      rationalize the stereochemical course of these 5-exo-trig cyclizations. Finally,
      an illustration of the value of this methodology was proposed with the synthesis
      of the A-B-C tricyclic unit of polyketide hexacyclinic acid 3a.

PMID- 16277320
TI  - Bis(pyrrol-2-yl)arylenes from the tandem bidirectional addition of vinyl Grignard
      reagent to aryl diesters.
AB  - [Chemical reaction: See text] A practical three-step synthesis of bis(pyrrol-2
      yl)arylenes has been accomplished, featuring a copper-catalyzed tandem
      bidirectional addition of vinylmagnesium bromide to aryldicarboxylates.
      Spectroscopic and cyclic voltammetric analyses revealed the influence of the
      central aromatic core and pyrrole substitution pattern on the electrochemical
      properties of these comonomers.

PMID- 16277321
TI  - Synthesis of enantiomerically pure (purin-6-yl)phenylalanines and their
      nucleosides, a novel type of purine-amino acid conjugates.
AB  - [Chemical reaction: See text] Enantiomerically or diastereomerically pure 4
      (purin-6-yl)phenylalanines, a novel type of stable amino acid-purine conjugates,
      were synthesized by palladium-catalyzed cross-coupling reactions of protected 4
      boronophenylalanines or 4-(trimethylstanyl)phenylalanines with diverse 6
      halopurines (9-benzyl-6-halopurines and 9-(tetrahydropyran-2-yl)-6-halopurines as
      well as acyl- and silyl-protected 6-halopurine ribonucleosides and 2
      deoxyribonucleosides). Free purine bases and nucleosides bearing (S)- or (R)
      phenylalanine in position 6 were obtained after complete deprotection of the
      products of cross-coupling reactions. Reactivity trends for both of these cross
      coupling and deprotection protocols have been compared in terms of
      practicability, efficiency, and stereoselectivity.

PMID- 16277322
TI  - A study of the stereochemistry of 2-aryl-4,5-dimethyl-1,3-dioxolanes by
      cholesteric induction in nematic phases and circular dichroism spectroscopy.
AB  - [Chemical reaction: See text] The circular dichroism spectra and the twisting
      ability of a series of 2-aryl-4,5-dimethyl-1,3-dioxolanes used as dopants in
      nematic solvents have been related to their absolute configuration. Whereas the
      circular dichroism (CD) spectra are deeply affected by the substituents present
      in the aromatic ring, which in several cases cause sign inversion, the helical
      twisting power beta is only marginally influenced. The values of beta also seem
      not very sensitive to the rotamer population around the aromatic ring; this
      indicates the predominant importance of the chiral dioxolane ring in determining
      the cholesteric induction. These facts can be explained by the different nature
      of the two observables: in CD, the chirality is read by the absorbing chromophore
      and is deeply influenced even by small changes of this group. In cholesteric
      induction we are dealing instead with chiral solute-solvent interactions that
      determine a twist in the solvent. In light of the present and previous results,
      this process seems predominantly determined by short-range interactions, which
      are modulated by the molecular shape. From a practical point of view, a
      configurational correlation using CD for the present series of compounds seems
      problematic, while the values of beta are nicely correlated to the absolute
      configurations. Calculations with the surface chirality method predict well the
      sign and order of magnitude of beta and their limited sensitivity to the phenyl
      substituents and rotamer population.

PMID- 16277323
TI  - Indirect electroreductive cyclization and electrohydrocyclization using catalytic
      reduced nickel(II) salen.
AB  - [Chemical reaction: See text] We describe efforts to achieve the electroreductive
      cyclization (ERC) and the electrohydrocyclization (EHC) reactions using catalytic
      nickel(II) salen as a mediator. While nickel(II) salen proved effective, the
      analogous cobalt complex as well as nickel(II) cyclam were not. The
      transformations were achieved in yields ranging from 60 to 94% using either a
      mercury pool or an environmentally preferable reticulated vitreous carbon (RVC)
      cathode. These examples represent the first instances wherein a nickel salen
      complex has been used in this manner. Clear differences between the voltammetric
      behavior of the ERC and EHC substrates were observed. The bisenoate 14, for
      example, displays a substantially larger catalytic current. When the structurally
      modified mediator 31 was used, the electron-transfer pathway shuts down. Instead,
      the reduced form of 31 behaves as an electrogenerated base, leading to the
      formation of the intramolecular Michael adduct 23. Presumably, the methyl groups
      of the modified ligand diminish the ability of the reduced form of the complex to
      serve as a nucleophile but not as a base. Aldehyde 23 was also characterized as a
      side product of the nickel(II) salen mediated electroreductive cyclization of 11.
      Given that it is absent from nonmediated processes, its formation is linked to
      the presence of the mediator. To account for the results, we favor the existence
      of a mechanistic continuum involving an equilibrium between nickel(II) salen (15)
      and two reduced forms, one being the metal-centered species 16, the other being a
      ligand-centered species 17. We postulate that one form may be more prominently
      involved with the chemistry than another, depending upon the electronic
      properties/requirements of the substrate, and suggest that the equilibrium will
      shift to accommodate the need. Thus, for a hard electrophile like an alkyl
      halide, the properties of 16 ought to dominate, whereas 17 ought to predominate
      as the reactive species accounting for the chemistry described herein since it
      properly matches a soft ligand-centered nucleophile with a soft electron
      deficient alkene.

PMID- 16277324
TI  - Stereoselective syntheses of highly functionalized bicyclo[3.1.0]hexanes: a
      general methodology for the synthesis of potent and selective mGluR2/3 agonists.
AB  - [Chemical reaction: See text] A Et3Al mediated intramolecular epoxide opening,
      cyclopropanation reaction is described. The transformation provided highly
      functionalized bicyclo[3.1.0]hexane systems in high efficiency and with perfect H
      or F endo selectivity. Application of this reaction to the synthesis of mGluR2/3
      agonist 1 (43% overall yield) and a few intermediates suitable for the synthesis
      of other bicyclo[3.1.0]hexane mGluR2/3 agonists is discussed.

PMID- 16277326
TI  - A diastereoselective and general route to 5-amino-5-deoxysugars: influence of C-3
      substitution on the addition of amines to C-5 of vinyl sulfone-modified hex-5
      enofuranosyl carbohydrates.
AB  - In the synthesis of vinyl sulfone-modified hex-5-enofuranosides, the E/Z ratios
      of the products are influenced by the stereoelectronic property of a group
      present at the C-3 position. This observation has been utilized to influence the
      diastereoselectivity of addition of amines to C-5 of vinyl sulfone- modified hex
      5-enofuranosides, which are efficient Michael acceptors. The stereoelectronic
      effect of OMe attached to the beta-face of C-3 (gluco derivative) is sufficient
      to impose diastereoselectivity overwhelmingly in favor of l-ido-aminosugars when
      the Michael acceptor is reacted with both primary and secondary amines. 3-O
      Benzylated gluco derivative is also effective in producing l-ido-aminosugars but
      only in reactions with primary amines. The selectivity is lost when an allo
      derivative with OBn at the alpha-face of C-3 is used. Selected products were
      desulfonated to establish this new approach as a general and versatile strategy
      for accessing 5-amino-5-deoxysugars.

PMID- 16277325
TI  - [3 + 2]-annulation reactions of chiral allylsilanes and chiral aldehydes. studies
      on the synthesis of bis-tetrahydrofuran substructures of annonaceous acetogenins.
AB  - [Structure: See text] Double asymmetric [3 + 2]-annulation reactions of chiral
      beta-silyloxyallylsilanes with chiral 2-tetrahydrofuranyl carboxaldehydes have
      been studied, leading to the stereocontrolled synthesis of six diastereomeric bis
      tetrahydrofuran structures corresponding to the core subunits of members of the
      Annonaceous acetogenin family of natural products. Transition-state models are
      proposed to account for the stereoselectivity of the double-stereodifferentiating
      [3 + 2]-annulation reactions.

PMID- 16277327
TI  - 1,3-dipolar cycloaddition chemistry for the preparation of novel indolizinone
      based compounds.
AB  - [Chemical reaction: See text] Starting from methyl 5-oxo-6
      trifluoromethanesulfonyloxy-1,2,3,5-tetrahydroindolizine-8-carboxylate, obtained
      by a Rh(II)-catalyzed 1,3-dipolar cycloaddition reaction of 1-(2-benzenesulfonyl
      2-diazoacetyl)pyrrolidin-2-one and methyl acrylate, several indolo- and furano
      fused indolizinones were efficiently prepared. In the first case, a palladium
      mediated C-N coupling of the triflate with a variety of substituted anilines
      provided the desired methyl 5-oxo-6-(arylamino)-1,2,3,5-tetrahydroindolizine-8
      carboxylates in high yield. Methyl 6-(2-bromophenylamino)-5-oxo-1,2,3,5
      tetrahydroindolizine-8-carboxylate as well as its decarboxylated analogue, 6-(2
      bromophenylamino)-2,3-dihydro-1H-indolizin-5-one, were synthesized in excellent
      yield and were found to undergo an intramolecular Heck cyclization to give
      1,2,3,6-tetrahydroindolizino[6,7-b]indol-5-ones. To prepare furano-fused
      indolizinones, methyl 6-hydroxy-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylate
      was etherified with different allyl halides, and the resultant allyl ethers were
      subjected to a thermal Claisen rearrangement to give the corresponding methyl 7
      allyl-6-hydroxy-5-oxo-1,2,3,4-tetrahydroindolizine-8-carboxylates. Cyclization
      under Wacker oxidation conditions afforded methyl 2-methyl-8-oxo-5,6,7,8
      tetrahydro-1-oxa-7a-aza-s-indacene-4-carboxylates in near-quantitative yield.

PMID- 16277328
TI  - First synthesis of the beta-D-rhamnosylated trisaccharide repeating unit of the O
      antigen from Xanthomonas campestris pv. campestris 8004.
AB  - The trisaccharide repeating unit of the O-antigen of the lipopolysaccharide from
      Xanthomonas campestris pv. campestris 8004, a pathogen of cruciferous crops,
      presents some structural features that renders it a challenging synthetic target:
      the presence of a beta-D-rhamnosidic linkage, the steric crowd on a 1,2-cis
      diglycosylated D-rhamnose, and finally the noncommercial availability of its
      monosaccharide constituents. The synthesis of this trisaccharide as methyl
      glycoside has been accomplished by exploiting a strategy whose key steps were the
      sequential beta-D-rhamnosylation with a 2-O-benzylsulfonyl-N
      phenyltrifluoroacetimidate donor, debenzylsulfonylation, and coupling with a D
      Fucp3NAc thioglycoside donor.

PMID- 16277330
TI  - Ruthenium(II) complexes of monodonor ligands: efficient reagents for asymmetric
      ketone hydrogenation.
AB  - [Chemical reaction: See text] A series of BINOL-derived ligands have been
      prepared and incorporated into ruthenium(II) complexes containing a diamine
      ligand. The complexes have proven to be excellent catalysts for the asymmetric
      hydrogenation of ketones, giving reduction products with enantiomeric excesses of
      up to 99%.

PMID- 16277329
TI  - Water-soluble calix[4]resorcarenes as enantioselective NMR shift reagents for
      aromatic compounds.
AB  - A tetra L-prolinylmethyl derivative of a tetra-sulfonated calix[4]resorcarene (1)
      is an effective chiral NMR solvating agent for water-soluble compounds with
      phenyl, pyridyl, bicyclic aromatic, or indole rings. These aromatic compounds
      form host-guest complexes with the calix[4]resorcarene in water. Complexation of
      substrates with the calix[4]resorcarene is likely promoted by hydrophobic
      effects, and bicyclic substrates have association constants with the
      calix[4]resorcarene larger than those of similar phenyl-containing compounds.
      Aromatic resonances of the substrates show substantial upfield shifts because of
      shielding from the aromatic rings of the calix[4]resorcarene, and several
      resonances in the 1H NMR spectra typically exhibit enantiomeric discrimination.
      The extent of enantiomeric discrimination depends in part on interactions of the
      substituent groups of the substrates with the prolinylmethyl groups of the
      calix[4]resorcarene. The effectiveness of a calix[4]resorcarene prepared from N
      methyl-L-alanine (2) as a chiral NMR discriminating agent is compared to the L
      prolinylmethyl derivative.

PMID- 16277331
TI  - Kinetics and mechanism of the anilinolysis of aryl 4-nitrophenyl carbonates in
      aqueous ethanol.
AB  - [Chemical reaction: See text] The reactions of anilines with 4-nitrophenyl, 4
      methylphenyl, and 4-chlorophenyl 4-nitrophenyl carbonates (BNPC, MPNPC and
      ClPNPC, respectively) are studied kinetically in 44 wt % ethanol-water, at 25.0
      degrees C, with an ionic strength of 0.2 M (KCl). Plots of k(obsd) vs [amine] are
      linear, with the slopes (kN) independent of pH. The Bronsted-type plots (log k(N)
      vs pKa of conjugate acids of anilines) are linear, with slopes beta = 0.65, 0.85,
      and 0.78 for the reactions of anilines with BNPC, MPNPC, and ClPNPC,
      respectively. The values of the slopes for the two latter reactions are in
      accordance with those obtained in stepwise mechanism where breakdown to product
      of a zwitterionic tetrahedral intermediate is the rate-determining step. On the
      other hand, the beta value for the reactions of BNPC is at the upper limit of
      those found for concerted mechanisms. The kinetic results for the reactions of
      anilines with BNPC correlates well with those for the concerted reactions of the
      same amines with 4-methylphenyl and 4-chlorophenyl 2,4-dinitrophenyl carbonates:
      A plot of the calculated log k(N) values (through a multiple parametric equation)
      vs the experimental log k(N) values is linear with unity slope and zero
      intercept, which confirms the concerted mechanism for the latter three reactions.

PMID- 16277332
TI  - A linchpin approach to unsaturated fatty acids: 11,12-epoxyeicosatrienoic acid
      and 11S,12S-dihydroxyeicosatrienoic acid ethyl esters.
AB  - [Chemical reaction: See text] A "linchpin" coupling strategy is described for the
      construction of long-chain fatty acid metabolites. This strategy led to a short
      synthesis of the ethyl esters of both 11,12-epoxyeicosatrienoic acid (EET) and
      11S,12S-dihydroxyeicosatrienoic acid (DHET).

PMID- 16277333
TI  - Transition-metal-mediated cascade reactions: the water-accelerated
      carboalumination-Claisen rearrangement-carbonyl addition reaction.
AB  - [Chemical reaction: See text] A three-step cascade reaction involving a water
      accelerated catalytic carboalumination, a Claisen rearrangement, and a
      nucleophilic carbonyl addition converts terminal alkynes and allyl vinyl ethers
      into allylic alcohols containing up to three contiguous asymmetric carbon
      centers. Stoichiometric quantities of water as an additive increase the rate of
      the [3,3] sigmatropic rearrangement as well as the diastereoselectivity of the
      carbonyl addition process. Reaction products contain 1,6-diene functionalities
      that are readily cyclized to substituted cyclopentenes. An extension of this
      methodology to a sequence involving a [1,3] sigmatropic shift was feasible with a
      cyclopropylmethyl vinyl ether substrate.

PMID- 16277334
TI  - Enantioselective synthesis of the optically active alpha-methylene-beta-hydroxy
      esters, equivalent compounds to Morita-Baylis-Hillman adducts, using successive
      asymmetric aldol reaction and oxidative deselenization.
AB  - [Chemical reaction: See text] The asymmetric aldol reaction of a tetra
      substituted ketene silyl acetal including an alkylseleno group with aldehydes has
      been developed by the promotion of Sn(OTf)2 coordinated with a chiral diamine to
      afford the corresponding aldols having chiral quaternary centers at the alpha
      positions. The facile oxidative deselenization of these aldol compounds produces
      optically active alpha-methylene-beta-hydroxy esters which correspond to adducts
      prepared by the asymmetric Morita-Baylis-Hillman reaction.

PMID- 16277335
TI  - Copper-catalyzed arylation of amines using diphenyl pyrrolidine-2-phosphonate as
      the new ligand.
AB  - [Chemical reaction: See text] We have developed a general, efficient, and
      inexpensive catalyst system for arylation of amines by using 10 mol % of CuI as
      the copper source, 20 mol % of diphenyl pyrrolidine-2-phosphonate (DPP) as the
      ligand, K3PO4 as the base, and DMF containing 2% water (v/v) as the solvent.

PMID- 16277336
TI  - G3(MP2) ring strain in bicyclic phosphorus heterocycles and their hydrocarbon
      analogues.
AB  - [Figure: see text] The ring strain present in 2-aza-1
      phosphabicyclo[n.1.0]alka(e)nes (n = 1-5) is calculated at the G3(MP2) level
      using homodesmotic reactions. The influence of cyclopropa(e)nation and heteroatom
      substitution is analyzed by a comparison with the corresponding bicyclic
      hydrocarbons and separate ring systems. It is shown that the strain caused by
      fusion with a cyclopropane is the sum of the separate rings, whereas the strain
      resulting from fusion with cyclopropene leads to strain energies much larger than
      the sum of rings, as a result of the inverted nature of the bridgehead carbon. In
      all ring structures but one, cyclohexane, substitution by nitrogen and phosphorus
      is favorable and the effect is most pronounced for the most condensed structures.
      The calculated strain energies correlate very well with the experimental
      stability and reactivity of the bicyclic iron-amino phosphirane and phosphirene
      complexes.

PMID- 16277337
TI  - Arylsulfonate-based nucleophile assisting leaving groups.
AB  - [Chemical reaction: See text] The synthesis and unique reactivity of a series of
      arylsulfonate-based nucleophile assisting leaving groups (NALG) containing
      oligomeric ether units (including crown ethers) attached to the arylsulfonyl ring
      in the ortho orientation are described. The reactions of a variety of these ether
      containing alkyl sulfonates with metal halides proceeded at substantially greater
      rates than electronically similar sulfonates. These ether-containing leaving
      groups also displayed marked selectivity for lithium halides relative to the
      corresponding sodium and potassium salts in nucleophilic displacement reactions.

PMID- 16277339
TI  - Double diastereoselection in aldol reactions mediated by dicyclohexylchloroborane
      between chiral aldehydes and a chiral ethyl ketone derived from L-erythrulose.
      synthesis of a C1-C9 fragment of the structure of the antifungal metabolite
      soraphen A1alpha.
AB  - [Chemical reaction: See text] Both matched and mismatched diastereoselections
      have been observed in the aldol reactions of a range of chiral aldehydes with the
      dicyclohexylboron enolate of a chiral ethyl ketone related to L-erythrulose. As
      was previously observed in the corresponding aldol reactions with L-erythrulose
      derivatives, the Felkin-Anh model provides an adequate explanation for the
      stereochemical outcome of reactions with chiral alpha-methyl aldehydes. However,
      a satisfactory account of the results observed with alpha-oxygenated aldehydes
      was only possible with the Cornforth model. As a practical application of the
      methodology described herein, a C1-C9 fragment of the structure of the antifungal
      macrolide soraphen A1alpha has been prepared in a convergent and stereoselective
      way.

PMID- 16277338
TI  - Preparation and analysis of oligonucleotides containing the c4'-oxidized abasic
      site and related mechanistic probes.
AB  - The C4'-oxidized abasic site (C4-AP) is produced by a variety of DNA damaging
      agents. This alkali labile lesion can exist in up to four diastereomeric cyclic
      forms, in addition to the acyclic keto-aldehyde. Synthetic oligonucleotides
      containing the lesion were prepared from a stable photochemical precursor.
      Chemical integrity of the lesion containing oligonucleotides was probed using
      phosphodiesterase lability. Analysis of the 3',5'-phosphate diester of the
      monomeric lesion released from single diastereomers of photolabile precursors by
      1H NMR indicates that isomerization of the hemiacetal and/or hemiketal is rapid.
      The syntheses and characterization of oligonucleotides containing
      configurationally stable analogues of C4-AP, which serve as mechanistic probes
      for deciphering the structural basis of the biochemical and biological effects of
      the C4'-oxidized abasic lesion, are also described.

PMID- 16277341
TI  - N-thioacyl 1,3-amino alcohols: synthesis via ring-opening of oxiranes with
      thioamide dianions and applications as key intermediates leading to
      stereochemically defined 5,6-dihydro-4H-1,3-oxazines and 1,3-amino alcohols.
AB  - N-Thioacyl 1,3-amino alcohols were synthesized via the ring-opening of oxiranes
      with thioamide dianions generated from N-benzyl thioamides and BuLi in a highly
      regio- and stereoselective manner. The diastereomers of N-thioacyl 1,3-amino
      alcohols were readily separated by column chromatography to give stereochemically
      defined N-thioacyl 1,3-amino alcohols. They underwent intramolecular cyclization
      with Bu4F and EtI to give 5,6-dihydro-4H-1,3-oxazines. The reaction was specific
      with anti-N-thioacyl 1,3-amino alcohols, and cis-5,6-dihydro-4H-1,3-oxazines were
      obtained with high efficiency, whereas the reaction of a syn-alcohol gave a
      thioimidate as a major product. The reduction of N-thioacyl 1,3-amino alcohols
      with LiAlH4gave N-alkyl 1,3-amino alcohols in high yields. The use of optically
      active propylene oxide as a starting material gave the corresponding oxazine and
      alcohols in optically pure forms.

PMID- 16277340
TI  - Synthesis of beta-substituted alpha-amino acids via Lewis acid promoted
      enantioselective radical conjugate additions.
AB  - [Chemical reaction: See text] Lewis acid promoted radical conjugate additions to
      beta-substituted alpha,beta-unsaturated alpha-nitro esters and amides were
      investigated. With achiral Lewis acids, there was competition between the desired
      radical conjugate addition and undesired alkene reduction mediated by Bu3nH. Zinc
      Lewis acids provided the greatest amounts of addition products with both
      substrate classes. Studies with Bu3nD indicated that the acidic alpha
      stereocenter of the alpha-nitro ester products does not racemize under controlled
      workup conditions. The corresponding alpha-nitro amides racemized significantly
      during chromatography, but this problem could be greatly minimized by subjecting
      the crude adducts to subsequent transformations. Indium-mediated reduction of the
      nitro group followed by acylation of the resulting amine provided good yields of
      beta-substituted alpha-amino acid derivatives with mimimal levels of
      racemization. Attempts to use chiral Lewis acids in a stereoselective variant of
      this process revealed that Kanemasa's DBFOX/Ph ligand (14a) was uniquely
      effective. Moderate to good ee's and low dr's were obtained with amide
      substrates. Determination of the absolute configurations of the syn and anti
      isomers of adduct 7b showed that the hydrogen atom abstraction step was
      significantly more stereoselective than the radical conjugate addition step. A
      model for substrate binding to the chiral Lewis acid is presented.

PMID- 16277342
TI  - Competitive stereochemical control operative during conrotatory
      electrocyclization of helically equilibrating diquinanyl-substituted 1,3,5,7
      octatetraenyl bisenolates.
AB  - [Carbohydrate structure: see text] Activation of the squarate ester cascade by
      adding the lithiated bicyclo[3.3.0]octene 20 and vinyllithium sequentially to 1
      results in the isolation of the four tetracyclic products 21-24. The structures
      of the topographically complex products were deduced by 2D NMR spectroscopy and X
      ray diffraction studies. The mechanistic insights gained by these findings are
      discussed. The product distribution is telltale evidence for predominant 1,2
      addition of the second alkenyl anion. Product stereochemistry is in turn
      diagnostic of the preferred mode of conrotatory ring closure operating within
      equilibrating helical intermediates of opposite pitch. A competing pathway for
      the elimination of methanol in these highly functionalized intermediates has been
      observed for the first time.

PMID- 16277344
TI  - Ring opening of 2,5-didehydrothiophene: structures and rearrangements of C4H2S
      isomers.
AB  - Electronic structures and rearrangement pathways of several C4H2S isomers are
      computationally investigated by methods based on coupled cluster theory and
      density functional theory. Six singlet C4H2S isomers lie within ca. 30 kcal/mol
      above butatrienethione (6), the apparent global minimum. Ethynylthioketene (7)
      lies only 2 kcal/mol higher in energy than cumulene 6. Two open-chain isomers,
      butadiynylthiol (8) and diethynyl sulfide (9), reside ca. 9 and 24 kcal/mol above
      6, respectively. Lying 30 kcal/mol above 6, two cyclic singlet isomers,
      ethynylthiirene (10) and cyclopropenylidenemethanthione (11), are nearly
      degenerate in energy. Thiophene-2,5-diyl (12) lies substantially higher in energy
      than 6 (ca. 45 kcal/mol) and is predicted to rearrange preferentially by C-S bond
      cleavage, leading to thioketene 7, rather than by C-C bond cleavage, leading to
      diethynyl sulfide (9; retro-Bergman cyclization). Accurate spectroscopic
      properties of these C4H2S isomers, as well as an understanding of their
      rearrangement pathways, should facilitate the detection and characterization of
      these isomers in the laboratory and the interstellar medium.

PMID- 16277345
TI  - Fast and stable photochromic oxazines.
AB  - We have designed and synthesized two photochromic compounds incorporating fused
      indoline and benzooxazine fragments. Variable-temperature 1H NMR spectroscopy
      demonstrates that their central [1,3]oxazine ring opens thermally with free
      energy barriers ranging from 14 to 19 kcal mol(-1). The ring-opened species
      reverts rapidly to the original isomer and can only be detected after chemical
      trapping. Specifically, the nucleophilic attack of a hydroxide anion to the
      indolium cation of the ring-opened species prevents re-isomerization. Laser
      excitation of both compounds induces the opening of the [1,3]oxazine ring in less
      than 6 ns with quantum yields up to 0.1. The photoinduced ring opening generates
      a 4-nitrophenolate chromophore, which absorbs strongly at 440 nm. The
      photogenerated species reverts to the original form with a lifetime of 22 ns for
      both compounds. Thus, these transformations can be exploited to interconvert the
      two isomers of each species with nanosecond switching speeds. Furthermore,
      thousands of switching cycles can be repeated consecutively without any sign of
      degradation, even in the presence of molecular oxygen. These processes can be
      reproduced efficiently in poly(methyl methacrylate) matrixes. Under these
      conditions, the thermal re-isomerization occurs with biexponential kinetics in
      submillisecond time scales. In principle, the fast isomerization kinetics and
      excellent fatigue resistance of both compounds offer the opportunity to modulate
      rapidly and efficiently a variety of molecular and macroscopic properties. Thus,
      our molecular design can evolve into the realization of a new family of
      photochromic compounds and materials with promising photoresponsive character.

PMID- 16277343
TI  - Design, synthesis, and biochemical evaluation of 1,5,6,7-tetrahydro-6,7-dioxo-9-D
      ribitylaminolumazines bearing alkyl phosphate substituents as inhibitors of
      lumazine synthase and riboflavin synthase.
AB  - The last two steps in the biosynthesis of riboflavin, an essential metabolite
      that is involved in electron transport, are catalyzed by lumazine synthase and
      riboflavin synthase. To obtain structural probes and inhibitors of these two
      enzymes, two ribityllumazinediones bearing alkyl phosphate substituents were
      synthesized. The synthesis involved the generation of the ribityl side chain, the
      phosphate side chain, and the lumazine system in protected form, followed by the
      simultaneous removal of three different types of protecting groups. The products
      were designed as intermediate analogue inhibitors of lumazine synthase that would
      bind to its phosphate-binding site as well as its lumazine binding site. Both
      compounds were found to be effective inhibitors of Bacillus subtilislumazine
      synthase as well as Escherichia coli riboflavin synthase. Molecular modeling of
      the binding of one of the two compounds provided a structural explanation for how
      these compounds are able to effectively inhibit both enzymes. In phosphate-free
      buffer, the phosphate moieties of the inhibitors were found to contribute
      positively to their binding to Mycobacterium tuberculosis lumazine synthase,
      resulting in very potent inhibitors with Ki values in the low nanomolar range.
      The additional carbonyl in the dioxolumazine system versus the purinetrione
      system was found to make a positive contribution to its binding to E. coli
      riboflavin synthase.

PMID- 16277346
TI  - Feigrisolide C: structural revision and synthesis.
AB  - [Carbohydrate structure: see text] The original macrodiolide structure proposed
      for feigrisolide C was incorrect. The true structure of feigrisolide C was
      identified as (2'S,3'S,6'R,8'R)-homononactoyl (2R,3R,6S,8S)-nonactic acid, which
      was confirmed by total synthesis.

PMID- 16277347
TI  - Determination of the polarities of some ionic liquids using 2-nitrocyclohexanone
      as the probe.
AB  - Solute-solvent interactions on the keto-enol tautomerism of 2-nitrocyclohexanone
      in several organic solvents and room-temperature ionic liquids (RTILs) have been
      analyzed in terms of multiparameter equations. Permittivity and cohesive pressure
      values of the RTILs, unavailable by direct measurements, have been derived.

PMID- 16277349
TI  - Formation of radical anions and not deprotonation starts the reaction of gamma
      butyrolactone with potassium anions.
AB  - A mechanism is proposed for the reaction of gamma-butyrolactone with the
      potassium anion as a two-electron-transfer reagent. Potassium hydride and
      potassium 4-potassiobutyrate are formed in this process as intermediates. These
      compounds deprotonate gamma-butyrolactone. Potassium lactone enolate, potassium
      butyrate, and hydrogen are the final reaction products.

PMID- 16277348
TI  - Synthesis of double C-glycoside analogue of sTn.
AB  - A sTn double C-glycoside, sTn analogue 2, was synthesized using samarium
      chemistry developed in our laboratory. Complications in the oxidation reaction
      affording aldehyde acceptor were overcome by double protection of amide and the
      use of a room-temperature ionic liquid as solvent. Studies are underway to
      conjugate the sTn double C-glycoside hapten 2 to KLH carrier protein for
      biological evaluation as a vaccine.

PMID- 16277350
TI  - DABCO-catalyzed reaction of alpha-halo carbonyl compounds with dimethyl
      acetylenedicarboxylate: a novel method for the preparation of polysubstituted
      furans and highly functionalized 2H-pyrans.
AB  - [Chemical reaction: see text] Polysubstituted furans and highly functionalized 2H
      pyrans were prepared in good yields by DABCO-catalyzed reactions of alpha-halo
      carbonyl compounds with dimethyl acetylenedicarboxylate (DMAD) at room
      temperature.

PMID- 16277351
TI  - Versatile access to C-4-substituted 2-amino-1,3-azoles from hydropyridines in
      oxidative conditions.
AB  - [Chemical reaction: see text] Various substituted 2-aminotetrahydroazolopyridines
      and 2-aminohexahydroazolopyridines have been prepared by bromine-mediated
      addition of protected guanidine or urea to hydropyridine derivatives. The pH
      dependent regioselective cleavage of the resulting aminal function led to the 2
      aminoazole products III. The yields of the bicycles of type II, and their
      conversion into azoles III depends on the electronic properties of the
      substituents on the nitrogen of the tetrahydopyridine.

PMID- 16277352
TI  - Stereoselective synthesis of the C1-C13 fragment of 2,3-dihydrodorrigocin A.
AB  - [Chemical reaction: see text] The first synthesis of the C1-C13 fragment of 2,3
      dihydrodorrigocin A has been achieved from 6-bromohexanoic acid in 14 linear
      steps and an overall yield of 2%. The configurations of the stereogenic centers
      C8, C9, and C10 have been determined to be the same as for migrastatin.

PMID- 16277354
TI  - Convenient access to new chiral ferroceno-(iso)quinolines.
AB  - [Chemical reaction: see text] New chiral pyridine derivatives possessing the
      planar chirality of the ferrocene have been prepared by means of an aldolization
      crotonization reaction. This very simple reaction has been applied to the
      synthesis of isomers 1-4 that differ in the position of the nitrogen atom on the
      pyridine ring. Following the same procedure, asymmetric synthesis of 1 has been
      achieved using an enantiopure ferrocenylzinc intermediate. This method has also
      allowed the preparation of a chiral analogue of 2,2'-bipyridine.

PMID- 16277353
TI  - A carbohydrate-based approach for the total synthesis of 1,3-polyol/alpha-pyrone
      antifungal natural products.
AB  - [Chemical reaction: see text] An elimination and stereoselective hydrogenation of
      alpha-D-glucoheptonic-gamma-lactone derivative has been applied to prepare a
      differentially protected anti,anti-1,3,5-triol system, the utility of which has
      been extended for the total synthesis of anti-fungal 1,3-polyol/alpha-pyrone
      natural products.

PMID- 16277355
TI  - A short synthesis of 10-hydroxy 7-spirocyclopropanated camphor.
AB  - [Chemical reaction: see text] A short alternative synthesis of the title 10
      hydroxy 7-spirocyclopropanated camphor (4) en route to 10-hydroxycamphor (5) was
      achieved from cyclopentadiene-derived 4-benzyloxymethylspiro[2.4]hepta-4,6-diene
      (6a) by a facile regioselective Diels-Alder cycloaddition with 2
      chloroacrylonitrile in an overall yield of 20%.

PMID- 16277356
TI  - Synthesis of the glycosphingolipid beta-galactosyl ceramide and analogues via
      olefin cross metathesis.
AB  - The preparation of the glycosphingolipid galactosyl ceramide from an orthogonally
      protected five-carbon building block is described. The main chain of the lipid is
      installed via a highly stereoselective olefin cross metathesis reaction. The
      methodology permits the facile preparation of glycolipids which vary in the
      length of the main carbon chain.

PMID- 16277358
TI  - Reactivity of Grubbs' catalysts with urea- and amide-substituted olefins.
      Metathesis and isomerization.
AB  - [Chemical reaction: see text] The reactions of a series of urea- and amide
      substituted olefins with Grubbs' catalysts are presented. Depending on the
      substrate's nature, the formation of either cross-metathesis or isomerization
      products is observed. To favor the cross-metathesis products, the reactions have
      been carried out using a wide range of experimental conditions. Upon addition of
      monophenyl phosphoester to these reactions, the isomerization of the olefins is
      completely suppressed and the cross-metathesis products are obtained in up to 60%
      yield.

PMID- 16277357
TI  - Modular total synthesis of lamellarin D.
AB  - [Chemical reaction: see text] A modular total synthesis of lamellarin D, a marine
      alkaloid with potent cytotoxic as well as topoisomerase I inhibition properties,
      has been accomplished. A sequential and regioselective bromination/Suzuki cross
      coupling procedure was applied for the introduction of aryl groups at positions 1
      and 2 of scaffold 1. Microwave-assisted 2,3-dichloro-5,6-dicyano-p-benzoquinone
      (DDQ) oxidation to yield pyrroloisoquinoline 15, followed by phenol group
      deprotection and subsequent lactonization, gave lamellarin D (18% in eight steps
      from 1).

PMID- 16277359
TI  - Michael-Stork addition of cyclopentyl enamine to allenyl ketones and esters.
AB  - [Chemical reaction: see text] We report the first examples of a Michael-Stork
      enamine addition to allenyl esters and ketones. Studies reveal that 2 equivalents
      of enamine are required for optimal yields. In the case of an allenyl methyl
      ketone, cyclopentyl enamine addition led to 8-oxobicyclo[3.2.1]octane formation,
      providing evidence for the in situ formation of an enamine intermediate following
      the initial Michael-Stork reaction.

PMID- 16277360
TI  - Diastereoselective synthesis of pyrrolidines via the Yb(OTf)3 catalyzed three
      component reaction of aldehydes, amines, and 1,1-cyclopropanediesters.
AB  - [Chemical reaction: see text] Aldimines, generated in situ by the reaction of
      primary amines or anilines with aldehydes, undergo smooth reaction with various
      1,1-cyclopropanediesters in the presence of catalytic Yb(OTf)3. The products are
      pyrrolidines in which the major diastereomer bears a cis relationship between
      substituents at the 2- and 5-positions. In most cases the diastereoselectivity is
      greater than 10:1.

PMID- 16277361
TI  - Zinc-mediated ring-expansion and chain-extension reactions of beta-keto esters.
AB  - [Chemical reaction: see text] The reaction of cyclic beta-keto esters with
      CF3CO2ZnCH2I provided the corresponding ring-expanded products in moderate to
      good yields. Although alpha-substituted acyclic beta-keto esters reacted with
      much less efficient, chain-extension reaction of simple beta-keto esters also
      proceeded effectively to generate gamma-keto esters in high yields.

PMID- 16277362
TI  - Chain elongation of aldoses by indium-mediated coupling with 3-bromopropenyl
      esters.
AB  - [Chemical reaction: see text] A procedure is described for acyloxyallylation of
      unprotected aldoses with two functionalized reagents: 3-bromopropenyl acetate and
      3-bromopropenyl benzoate. The reaction is performed in ethanol or a dioxane/water
      mixture in the presence of indium metal. The products are deesterified in the
      workup to afford unsaturated polyols, which are isolated as mixtures of two
      diastereomers. The major diastereomers are subjected to ozonolysis to afford new
      aldoses, which have been elongated by two carbon atoms compared to the starting
      materials. The new aldoses all have lyxo configuration at positions 2, 3, and 4.

PMID- 16277363
TI  - Radical promoted Wagner-Meerwein-type rearrangement of epoxides in camphoric
      systems using a Ti(III) radical source.
AB  - [Chemical reaction: see text] A radical based Wagner-Meerwein-type rearrangement
      has been observed in camphoric systems. The radical was generated from the
      epoxide using Cp2TiCl as the radical source. The radical initiator Cp2TiCl was
      prepared in situ from commercially available Cp2TiCl2 and Zn dust in THF under
      argon.

PMID- 16277367
TI  - Alpha-amido sulfones as stable precursors of reactive N-acylimino derivatives.

PMID- 16277369
TI  - Single-reference ab initio methods for the calculation of excited states of large
      molecules.

PMID- 16277368
TI  - Ag(I) N-heterocyclic carbene complexes: synthesis, structure, and application.

PMID- 16277370
TI  - Catalytic versatility, stability, and evolution of the (betaalpha)8-barrel enzyme
      fold.

PMID- 16277371
TI  - Filamentous phage display in the new millennium.

PMID- 16277372
TI  - "Bound but not gagged"--immobilizing single-site alpha-olefin polymerization
      catalysts.

PMID- 16277373
TI  - Ionic liquid crystals.

PMID- 16277374
TI  - Surface chemistry of biodegradable polymers for drug delivery systems.

PMID- 16277376
TI  - Tetramethylammonium hydroxide (TMAH) thermochemolysis of lignin: behavior of 4-O
      etherified cinnamyl alcohols and aldehydes.
AB  - The thermochemolytic behavior of 4-O-etherified cinnamyl alcohols and aldehydes
      in lignin was investigated in the presence of tetramethylammonium hydroxide
      (TMAH) (315 degrees C/4 s), using veratrylglycol-beta-(coniferyl alcohol) ether
      (1a), veratrylglycol-beta-(sinapyl alcohol) ether (1b), and veratrylglycol-beta
      (coniferyl aldehyde) ether (2). The methylated products were monitored with gas
      chromatography-mass spectrometry. Dimers 1a and 1b provided the coniferyl and
      sinapyl alcohol dimethyl ethers consisting of three isomers, respectively.
      Coniferyl alcohol dimethyl ether isomers were also observed in the TMAH
      thermochemolysis pyrolysates of a bulk dehydrogenation polymer of coniferyl
      alcohol and a Japanese cedar (Cryptomeria japonica) wood. Coniferyl aldehyde
      methyl ether was not provided from TMAH thermochemolyses of coniferyl aldehyde,
      2, a dehydrogenation polymer of coniferyl aldehyde, and the cedar wood. The
      former three provided veratryl aldehyde in a large abundance, instead of
      coniferyl aldehyde methyl ether. Sinapyl aldehyde provided 3,4,5
      trimethoxybenzaldehyde in a large abundance and sinapyl aldehyde methyl ether in
      a trace abundance. The results showed that TMAH thermochemolysis is an effective
      tool to obtain information on cinnamyl alcohol end groups, but is not applicable
      to analysis of cinnamyl aldehyde end groups.

PMID- 16277377
TI  - Enzyme-electropolymer-based amperometric biosensors: an innovative platform for
      time-temperature integrators.
AB  - A novel exogenous time-temperature integrator (TTI) based on an amperometric
      glucose oxidase biosensor is presented. The TTI consists of the enzyme entrapped
      within an electrochemically generated poly(o-phenylenediamine) (PoPD) thin film
      deposited on the interior wall of a platinum (Pt) or a platinized stainless steel
      (Pt-SS) capsule. After thermal treatment, the TTI is mounted in a continuous flow
      system and connected to a potentiostat for amperometric detection of residual
      enzyme activity. A measurement is completed within 10 min. Isothermal treatments
      were carried out between 70 and 79.7 degrees C. Thermal inactivation of the
      immobilized enzyme followed apparent first-order kinetics with z values of 6.2 +/
      0.6 and 6.6 +/- 0.8 degrees C for Pt and Pt-SS capsules, respectively. These z
      values suggest that the proposed TTIs have the potential to assess pasteurization
      processes that target microorganism such as Listeria monocytogenes and
      Escherichia coli O157:H7.

PMID- 16277378
TI  - Differentiation of important and closely related cereal plant species (Poaceae)
      in food by hybridization to an oligonucleotide array.
AB  - We report the development of an oligonucleotide microarray for the simultaneous
      detection of six important cereal food plant species from the Poaceae based on
      the chloroplast trnL intron sequence. We used universal primers to amplify the
      trnL intron from wheat, rye, barley, oat, rice, and maize, followed by a cyclic
      labeling of oligonucleotides probes and subsequent hybridization to an
      oligonucleotide microarray. In single taxon analyses, positive signals were
      produced with a high signal-to-noise ratio. The assay also enabled the analysis
      of mixed samples. The results obtained for real food samples were in agreement
      with the ingredient labels, but positive results for grains not declared on the
      ingredients list were observed in three out of 10 samples, which indicates that
      the final products and/or the declared ingredients were probably botanically
      impure or contaminated. The combination of the sensitivity of a universal
      polymerase chain reaction with the specificity of the labeling reaction allows
      this protocol to be applied in routine analyses of food samples, as demonstrated
      by successful analysis of processed composite food products.

PMID- 16277379
TI  - Optimization of the analysis of flavor volatile compounds by liquid-liquid
      microextraction (LLME). Application to the aroma analysis of melons, peaches,
      grapes, strawberries, and tomatoes.
AB  - A fast method based on liquid-liquid microextraction (LLME) has been developed
      for the analysis of volatile compounds in fruit and vegetable juices. The method
      was tested in an aqueous solution containing 49 common flavor compounds typically
      found in fruit aroma. Influence on extraction yield of the salts used, their
      levels, and the time of extraction was investigated. The efficiency of n-propyl
      gallate to inhibit the formation of secondary compounds from lipids during the
      crushing of fruit tissues was also tested. The proposed method was then applied
      to several authentic samples such as melons, peaches, grapes, strawberries, and
      tomatoes. The advantages and limitations of LLME are discussed.

PMID- 16277380
TI  - A gas chromatography/electron ionization-mass spectrometry-selected ion
      monitoring method for determining the fatty acid pattern in food after formation
      of fatty acid methyl esters.
AB  - A method using gas chromatography/electron ionization-mass spectrometry (GC/EI
      MS) in the selected ion monitoring (SIM) mode was developed for the analysis of
      fatty acids as methyl esters (FAMEs) in order to determine their percentage
      contribution to the fatty acid profile in food. In the GC/EI-MS-SIM mode,
      saturated fatty acids were determined with m/z 87, monoenoic fatty acids were
      determined with m/z 74, and polyenoic fatty acids were determined via the sum of
      m/z 79 and m/z 81. The ratios of these fragment ions and the GC retention data
      provided additional information for tentative structural assignments. The 28 FAME
      standards tested provided similar results for the novel GC/EI-MS-SIM method and
      GC/EI-MS in the full scan mode, both of which were slightly worse than GC/flame
      ionization detection (FID). Analysis of sunflower oil, suet, and cod liver oil
      verified that both major and minor fatty acids (20-60% and down to 0.001%
      contribution to the fatty acid pattern) were determined with sufficient quality
      that justifies application of the GC/EI-MS-SIM method for the analysis of food
      samples. Furthermore, the method was approximately 20- or approximately 10-fold
      more sensitive than GC/EI-MS in the full scan mode or GC/FID, respectively. The
      method is suited for both quantitative purposes and fatty acid identification in
      samples where only low amounts of lipids are available.

PMID- 16277381
TI  - Determination of 12 type A and B trichothecenes in cereals by liquid
      chromatography-electrospray ionization tandem mass spectrometry.
AB  - A new sensitive method for the simultaneous determination of 12 trichothecenes
      (deoxynivalenol, nivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol,
      fusarenon X, T-2 toxin, HT-2 toxin, neosolaniol, monoacetoxyscirpenol,
      diacetoxyscirpenol, T-2 triol, and T-2 tetraol) by liquid chromatography
      electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) is presented. The
      development of the method and investigations on the matrix influence on the MS
      signal are described in particular. The matrix effect was thereby minimized by
      using an internal standard, a special mobile phase, and specific fragmentation
      parameters. The sample was extracted with acetonitrile/water (84:16, v/v), and
      the extract was cleaned up with a MycoSep 227 column. Quantification was based on
      the internal standard de-epoxy-deoxynivalenol. Calibration curves were linear
      between 16 and 1600 ng/g, and the limits of detection ranged from 0.18 to 5.0
      ng/g. The developed method was applied for the determination of trichothecenes in
      120 naturally contaminated wheat and oat samples.

PMID- 16277382
TI  - Determination of bisphenol A in canned foods by immunoaffinity chromatography,
      HPLC, and fluorescence detection.
AB  - Bisphenol A (BPA) concentrations were determined in canned beverages, fruits,
      vegetables, and fat-containing foodstuffs bought in Austrian supermarkets. The
      analysis method consisted of sol-gel immunoaffinity chromatography followed by
      high-performance liquid chromatography with fluorescence detection. With one
      exception traces of BPA were detected in all samples. BPA recovery strongly
      depended on the food matrix, ranging from 27% in goulash to 103% in a lemon soft
      drink. The results obtained allow a more realistic picture of the BPA exposure
      caused by cans with an epoxy resin protective coating because--in contrast to
      several previous studies--only those fractions of the can contents that are
      actually consumed were analyzed. BPA concentrations ranging from 0.1 ng/mL (lemon
      soft drink) to 38 ng/g (ready-to eat soup from Thailand) were significantly lower
      than the European Union migration limit of 0.6 mg of BPA/kg of food.

PMID- 16277384
TI  - On-line MS/MS monitoring of acrylamide generation in potato- and cereal-based
      systems.
AB  - An on-line MS/MS technique was used to study the generation of acrylamide in rye
      , wheat-, and potato-based systems during cooking. Acrylamide release to the gas
      phase was monitored continuously and was correlated with the acrylamide content
      of samples using a calibration based upon the partition of [1,2,3
      (13C3)]acrylamide. On-line results at 180 degrees C were compared with data
      relating to the same systems obtained through GC-MS analysis. Agreement between
      the two techniques was notable, both in terms of the temporal profiles of
      acrylamide generation and when comparing the relative magnitudes of results for
      potato, wheat, and rye determined by each method. The effects of pH (citric acid)
      and added amino acids (soy protein hydrolysate) on the generation of acrylamide
      in hydrated potato flake were modeled at 180 degrees C. It was concluded that a
      combined treatment of low levels of each additive could result in significant
      reductions in acrylamide, although the effects of such treatments on sensory
      properties such as color and flavor remain to be evaluated.

PMID- 16277383
TI  - Evaluation of the antioxidant capacity of individual phenolic compounds in virgin
      olive oil.
AB  - Virgin olive oil has a high resistance to oxidative deterioration due to its
      tryacylglycerol composition low in polyunsaturated fatty acids and due to the
      presence of a group of phenolic antioxidants composed mainly of polyphenols and
      tocopherols. We isolated several phenolic compounds of extra virgin olive oil
      (phenyl-ethyl alcohols, lignans, and secoiridoids) by semipreparative high
      performance liquid chromatography (HPLC) and identified them using ultraviolet,
      atmospheric pressure chemical ionization, and electrospray ionization MS
      detection. The purity of these extracts was confirmed by analytical HPLC using
      two different gradients. Finally, the antioxidant capacity of the isolated
      compounds was evaluated by measuring the radical scavenging effect on 1,1
      diphenyl-2-picrylhydrazyl radical, by accelerated oxidation in a lipid model
      system (OSI, oxidative stability instrument), and by an electrochemical method.

PMID- 16277385
TI  - Liquid chromatography-tandem mass spectrometry for the determination of protein
      bound residues in shrimp dosed with nitrofurans.
AB  - An analytical method was developed for the determination of bound residues of the
      nitrofuran drugs furazolidone, nitrofurazone, furaltadone, and nitrofurantoin
      with a sensitivity of 1 ppb in shrimp. In this procedure, shrimp tissue is
      prewashed with solvents followed by overnight acid hydrolysis, during which the
      side chains of the bound residues are released and simultaneously derivatized
      with 2-nitrobenzaldehyde. After liquid-liquid extraction cleanup, the derivatives
      are detected and quantitated using liquid chromatography-mass spectrometry/mass
      spectrometry (LC-MS/MS) with an atmospheric pressure chemical ionization
      interface. The method was validated using control shrimp fortified with each side
      chain analyte at 1, 2, and 4 ppb. Method accuracies were >80% with coefficients
      of variation of <20% for all four analytes. Tissues from dosed shrimp were
      assayed to demonstrate the effectiveness of the method for recovering bound
      residues of nitrofurans. In shrimp dosed with nitrofurans, nitrofurantoin
      exhibited the lowest level of bound residues.

PMID- 16277386
TI  - Inhibition of uropathogenic Escherichia coli by cranberry juice: a new
      antiadherence assay.
AB  - A combination of microplate technology and turbidity assessment for testing the
      adherence of P-fimbriated Escherichia coli to human uroepithelial cell line T24,
      validated with the addition of the known inhibitor 4-O-alpha-D-galactopyranosyl
      alpha-D-galactopyranose (galabiose), resulted in a high-throughput, biologically
      relevant assessment of cranberry (Vaccinium macrocarpon). P-fimbriated ATCC E.
      coli strains 25922, 29194, and 49161 were inhibited by galabiose. ATCC 29194, a
      representative urine isolate containing the papGII allele (Class II fimbrial
      adhesin) and demonstrating the most significant inhibition in the presence of
      galabiose, was chosen for further testing. In this assay, a low-polarity fraction
      of cranberry juice cocktail demonstrated dose-dependent inhibition of E. coli
      adherence. Reported here, for the first time in V. macrocarpon, are 1-O
      methylgalactose, prunin, and phlorizin, identified in an active fraction of
      cranberry juice concentrate. This in vitro assay will be useful for the
      standardization of cranberry dietary supplements and is currently being used for
      bioassay-guided fractionation of cranberry juice concentrate.

PMID- 16277387
TI  - Isolation and characterization of a novel immunomodulatory alpha-glucan-protein
      complex from the mycelium of Tricholoma matsutake in basidiomycetes.
AB  - Tricholoma matsutake, a high-class edible mushroom in Japan, has been reported to
      have excellent biological activities, but difficulty in cultivating the fruit
      bodies and limited bulk availability have restricted detailed studies. We have
      developed a method of culturing in tanks, enabling the bulk supply of the
      mycelia. The preparation (CM6271) exerts modulative effects on the immune
      competence of mice and rats. In this study, a sodium hydroxide extract of CM6271
      was defatted followed by fractionation with a combination of ion exchange
      chromatography and gel filtration in order to identify the components involved in
      the expression of the activity, and a single peak fraction (MPG-1) was obtained
      with reversed phase chromatography. MPG-1 was a glycoprotein (sugar:protein
      ratio, 94.3:5.7) with a relative molecular mass of 360 kDa, and the sugar moiety
      contained about 90% glucose. NMR spectra and methylation analysis revealed that
      the alpha-1,4-linkage was the predominant glucan linkage with alpha-1,6- and
      alpha-1,2-linkages in the minority. The amino acid composition in the protein
      moiety was rich in glutamine, alanine, asparagine, leucine, glycine, valine,
      serine, threonine, isoleucine, and proline. MPG-1 was resistant to degradation
      with amylase or protease. The oral administration of MPG-1 promoted, in a dose
      dependent manner, the recovery of the mouse natural killer cell activity and
      serum IL-12 level that had been reduced by the loading of restraint stress. The
      dose of MPG-1 (25 mg/kg) required for the expression of the effect decreases to
      1/12 of that of CM6271 (300 mg/kg). Furthermore, MPG-1 formed a complex with TGF
      beta1 in vitro, modulating the biological activity of TGF-beta1 by binding to its
      active form. These results indicate that the mycelium of T. matsutake contains a
      novel alpha-glucan-protein complex with immunomodulatory activities.

PMID- 16277388
TI  - Evaluation of the cytotoxicity, genotoxicity, mutagenicity, and antimutagenicity
      of propolis from Tucuman, Argentina.
AB  - This study evaluates the toxic, genotoxic/mutagenic, and antimutagenic effects of
      propolis extract from Amaicha del Valle, Tucuman, Argentina. The cytotoxicity
      assays carried out with the lethality test of Artemia salina revealed that the
      LD50 was around 100 microg/mL. Propolis extracts showed no toxicity to Salmonella
      typhimurium TA98 and TA100 strains and Allium cepa at concentrations that have
      antibiotic and antioxidant activities. Otherwise, for the testing doses, neither
      genotoxicity nor mutagenicity was found in any sample. The propolis extracts were
      able to inhibit the mutagenesis of isoquinoline (IQ) and 4-nitro o
      phenylenediamine (NPD) with ID50 values of 40 and 20 microg/plate, respectively.
      From this result, the studied propolis may be inferred to contain some chemical
      compounds capable of inhibiting the mutagenicity of direct-acting and indirect
      acting mutagens. A compound isolated from Amaicha del Valle propolis, 2',4'
      dihydroxychalcone, showed cytotoxic activity (LC50 values of 0.5 microg/mL) but
      was not genotoxic or mutagenic. Furthermore, this compound was able to inhibit
      the mutagenicity of IQ (ID50 values of 1 microg/plate) but was unable to inhibit
      the mutagenicity of NPD. Our results suggest a potential anticarcinogenic
      activity of Amaicha del Valle propolis and the chalcone isolated from it.

PMID- 16277389
TI  - Solid olive residues: insight into their phenolic composition.
AB  - Solid olive residues (SOR) are byproducts of the olive-milling process, but they
      have an increasing importance in the pharmaceutical industry due to their rich
      content of biophenols. Such compounds are studied widely for their antioxidant
      and antimicrobial activities, but there is a lack of information about their
      quantitative recovery. This research highlighted the key role played both by the
      selection of the cultivar and by the degree of olive fruit ripening on the
      phenolic content on the SOR. The extraction methods were selected to reach the
      best quantitative results mainly using a safe food solvent. In light of the
      results the Soxhlet extraction with ethanol could be proposed as preferential for
      a higher recovery of verbascoside and its analogues.

PMID- 16277390
TI  - Great differences in antioxidant properties exist between 56 apple cultivars and
      vegetation seasons.
AB  - The contents of ascorbate, thiols, and phenolic compounds and antioxidative
      enzyme activity were measured in the apple peel of 56 genotypes after harvest in
      two vegetation seasons, 2003 and 2004. The main reason of great interest in these
      bioactive compounds is their well-established physiological role in all living
      systems. The biggest differences between tested genotypes were noted for
      ascorbate peroxidase and glutathione reductase (GR) activity, followed by total
      ascorbate, phenolics, and glutathione concentration; the least difference was
      observed in the case of catalase. A large cultivar variation was noted in the
      anthocyanins and flavonols contents. Distinguishing the cultivars with the
      lowest, highest, relatively stable or those in which antioxidant content greatly
      differed depending on growing seasons was attempted. The GR activity is proposed
      as an environmental stress marker of apple fruit.

PMID- 16277391
TI  - Pea (Pisum sativum L.) protease inhibitors from the Bowman-Birk class influence
      the growth of human colorectal adenocarcinoma HT29 cells in vitro.
AB  - The Bowman-Birk trypsin-chymotrypsin inhibitor (BBI) from soybean has been
      described as a potential cancer chemopreventive agent. We have compared the
      effects of BBI with those of two variant recombinant pea (Pisum sativum L.) seed
      protease inhibitors, rTI1B and rTI2B, homologous to BBI but differing in
      inhibitory activity, on the growth of human colorectal adenocarcinoma HT29 cells
      in vitro. A significant and dose-dependent decrease in the growth of HT29 cells
      was observed using all protease inhibitors, with rTI1B showing the largest
      decrease (IC50 = 46 microM). Inclusion of the pan-caspase inhibitor, Boc-D-FMK,
      did not negate the effects of rTI1B or rTI2B in the cell assays. The relative
      effectiveness of rTI1B and rTI2B may correlate with a variant amino acid sequence
      within their respective chymotrypsin inhibitory domain, in agreement with a
      chymotrypsin-like protease as a potential target.

PMID- 16277393
TI  - Induction of detoxication enzymes in mice by naturally occurring allyl nitrile.
AB  - Little is known about whether glucosinolate-derived nitriles have the ability to
      increase phase 2 detoxication enzymes and glutathione (GSH) in vivo. In this
      study, the ability of allyl nitrile, a hydrolysis product of the glucosinolate
      sinigrin, to increase tissue levels of the phase 2 detoxication enzymes
      glutathione S-transferase and quinone reductase and GSH in a variety of mouse
      tissues was examined. At the lowest dose level (11.8 mg/kg/day), allyl nitrile
      showed inductive ability in the stomach and lungs. At 23.6 mg/kg/day, the
      inductive effect was observed in the stomach, rectum, urinary bladder, and lungs,
      whereas at 47.2 mg/kg/day, it was recorded in the stomach, rectum, urinary
      bladder, kidneys, and lungs. These results show that allyl nitrile displays its
      maximum potency in the stomach and lungs, which is of interest in light of
      epidemiological studies demonstrating an inverse association between crucifer
      intake and the incidence of stomach and lung cancers.

PMID- 16277392
TI  - Chemistry and bioactivity of royal jelly from Greece.
AB  - Twenty-five compounds were identified from the dichloromethane and methanol
      extracts of royal jelly from Greece. Among them, 16 compounds are reported for
      the first time as royal jelly constituents, whereas 7 of them are isolated for
      the first time as natural products. The 7 new compounds were fatty acid
      derivatives: 10-acetoxydecanoic acid (1), trans-10-acetoxydec-2-enoic acid (2),
      11-oxododecanoic acid (3), (11S)-hydroxydodecanoic acid (4), (10R,11R)
      dihydroxydodecanoic acid (5), 3,11-dihydroxydodecanoic acid (6), and (11S),12
      dihydroxydodecanoic acid (7). The structures of the isolated compounds were
      determined by spectroscopic methods, mainly by the concerted application of 1D
      and 2D NMR techniques (HMQC, HMBC) and mass spectrometry. The studied sample and
      the isolated compounds were tested for their antimicrobial activity against Gram
      positive and Gram-negative bacteria and fungi and exhibited interesting
      activities.

PMID- 16277394
TI  - Kinetic studies of lycopene isomerization in a tributyrin model system at gastric
      pH.
AB  - A semi-preparative HPLC method was developed in order to isolate and purify the
      13-cis-lycopene isomer in tomato-based materials. The result was compared with
      the naturally predominant all-trans-lycopene isomer, in terms of stability to
      gastric pH at physiological temperature in a tributyrin model system. Kinetic
      experiments confirmed that lycopene isomerization is a reversible reaction, and
      under these conditions the all-trans isomer is more stable than the 13-cis
      isomer. In addition, it was found that at gastric pH 13-cis-lycopene would
      predominantly isomerize to the all-trans form rather than undergo
      oxidation/breakdown. A simulation based on the rate constants calculated in the
      kinetic study indicated that at gastric pH the lycopene isomeric distribution
      aimed toward an equilibrium characterized by approx 16% 13-cis-, 16% 9-cis-, and
      68% all-trans-lycopene. This study suggests that pH-driven isomerization in the
      stomach is at least partially responsible for the relatively high cis-lycopene
      proportion found in vivo.

PMID- 16277395
TI  - Curcuma longa L. constituents inhibit sortase A and Staphylococcus aureus cell
      adhesion to fibronectin.
AB  - The inhibitory activity of Curcuma longa L. (turmeric) rhizome constituents
      against sortase A, a bacterial surface protein anchoring transpeptidase, from
      Staphylococcus aureus ATCC 6538p was evaluated. The activity of the isolated
      compounds (1-4) was compared to that of the positive control,p
      hydroxymecuribenzoic acid (pHMB). The biologically active components of C. longa
      rhizome were characterized by spectroscopic analysis as the curcuminoids curcumin
      (1), demethoxycurcumin (2), and bisdemethoxycurcumin (3). Curcumin was a potent
      inhibitor of sortase A, with an IC50 value of 13.8 +/- 0.7 microg/mL.
      Bisdemethoxycurcumin (IC50 = 31.9 +/- 1.2 microg/mL) and demethoxycurcumin (IC50
      = 23.8 +/- 0.6 microg/mL) were more effective than pHMB (IC50 = 40.6 +/- 1.2
      microg/mL). The three isolated compounds (1-3) showed no growth inhibitory
      activity against S. aureus strain Newman, with minimum inhibitory concentrations
      (MICs) greater than 200 microg/mL. Curcumin also exhibited potent inhibitory
      activity against S. aureus cell adhesion to fibronectin. The suppression of
      fibronectin-binding activity by curcumin highlights its potential for the
      treatment of S. aureus infections via inhibition of sortase activity. These
      results indicate that curcumin is a possible candidate in the development of a
      bacterial sortase A inhibitor.

PMID- 16277396
TI  - Isoflavonoids isolated from Cuban propolis.
AB  - Chemical investigation of a red-type Cuban propolis sample has led to the
      isolation of 11 isoflavonoids (2 isoflavones, 3 isoflavans, and 6 pterocarpans),
      together with gallic acid, isoliquiritigenin, and (-)-liquiritigenin. Structural
      determination, including the absolute stereochemistry, was accomplished by
      spectroscopic analysis, particularly CD and 2D NMR techniques. The fragmentation
      behavior of pterocarpans was studied by electrospray ionization (ESI) tandem mass
      spectrometry (MS/MS) using an ion-trap analyzer, and a generalized fragmentation
      pathway, useful in the identification and structural characterization of
      pterocarpans, is proposed. Isoflavonoids are reported for the first time from
      propolis samples.

PMID- 16277397
TI  - Biodegradable composites from sugar beet pulp and poly(lactic acid).
AB  - Sugar beet pulp and poly(lactic acid) (PLA) composites were prepared by
      compression-heating. The resultant thermoplastics had a lower density, but they
      had tensile strength similar to that of pure PLA specimens as well as the same
      geometric properties. Tensile properties depended on the initial water content of
      sugar beet pulp and the process by which composites were manufactured. In
      comparison with sugar beet pulp, the composite showed improved water resistance.
      This can be attributed to the hydrophobic character of PLA and pulp-matrix
      interactions. The composite thermoplastics showed suitable properties for
      potential use as lightweight construction materials.

PMID- 16277398
TI  - Transgenic expression of bean alpha-amylase inhibitor in peas results in altered
      structure and immunogenicity.
AB  - The development of modern gene technologies allows for the expression of
      recombinant proteins in non-native hosts. Diversity in translational and post
      translational modification pathways between species could potentially lead to
      discrete changes in the molecular architecture of the expressed protein and
      subsequent cellular function and antigenicity. Here, we show that transgenic
      expression of a plant protein (alpha-amylase inhibitor-1 from the common bean
      (Phaseolus vulgaris L. cv. Tendergreen)) in a non-native host (transgenic pea
      (Pisum sativum L.)) led to the synthesis of a structurally modified form of this
      inhibitor. Employing models of inflammation, we demonstrated in mice that
      consumption of the modified alphaAI and not the native form predisposed to
      antigen-specific CD4+ Th2-type inflammation. Furthermore, consumption of the
      modified alphaAI concurrently with other heterogeneous proteins promoted
      immunological cross priming, which then elicited specific immunoreactivity of
      these proteins. Thus, transgenic expression of non-native proteins in plants may
      lead to the synthesis of structural variants possessing altered immunogenicity.

PMID- 16277399
TI  - Reversible precipitation of casein micelles with a cationic
      hydroxyethylcellulose.
AB  - The cationic hydroxyethylcellulose Polyquaternium 10 (PQ10) was found to produce
      a dose-dependent destabilization of casein micelles from whole or skim milk
      without affecting the stability of most of the whey proteins. The anionic
      phosphate residues on caseins were not determinant in the observed interaction
      since the destabilization was also observed with dephosphorylated caseins to the
      same extent. However, the precipitation process was completely inhibited by
      rising NaCl concentration, indicating an important role of electrostatic
      interactions. Furthermore, the addition of 150 mM NaCl solubilized preformed PQ10
      casein complexes, rendering a stable casein suspension without a disruption of
      the internal micellar structure as determined by dynamic light scattering. This
      casein preparation was found to contain most of the Ca2+ and only 10% of the
      lactose originally present in milk and remained as a stable suspension for at
      least 4 months at 4 degrees C. The final concentration of PQ10 determined both
      the size of the casein-polymer aggregates and the amount of milkfat that
      coprecipitates. The presence of PQ10 in the aggregates did not inhibit the
      activity of rennet or gastrointestinal proteases and lipases, nor did it affect
      the growth of several fermentative bacteria. The cationic cellulose PQ10 may
      cause a reversible electrostatic precipitation of casein micelles without
      disrupting their internal structure. The reversibility of the interaction
      described opens the possibility of using this cationic polysaccharide to
      concentrate and resuspend casein micelles from whole or skim milk in the
      production of new fiber-enriched lactose-reduced calcium-caseinate dairy
      products.

PMID- 16277400
TI  - Induction of apoptosis by 1-(2-hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione
      through reactive oxygen species production, GADD153 expression, and caspases
      activation in human epidermoid carcinoma cells.
AB  - This study examined the growth inhibitory effects of the structurally related
      beta-diketones compounds in human cancer cells. Here, we report that 1-(2-hydroxy
      5-methylphenyl)-3-phenyl-1,3-propanedione (HMDB) induces growth inhibition of
      human cancer cells and induction of apoptosis in A431 cells through modulation of
      mitochondrial functions regulated by reactive oxygen species (ROS). ROS
      generation occurs in the early stages of HMDB-induced apoptosis, preceding
      cytochrome c release, caspase activation, and DNA fragmentation. The changes
      occurred after single breaks in DNA were detected, suggesting that HMDB induced
      irreparable DNA damage, which in turn triggered the process of apoptosis. Up
      regulation of Bad and p21; down-regulation of Bcl-2, Bcl-XL, Bid, p53, and fatty
      acid synthase; and cleavage of Bax were found in HMDB-treated A431 cells.
      Glutathione and N-acetylcysteine (NAC) suppress HMDB-induced apoptosis. HMDB
      markedly enhanced growth arrest DNA damage inducible gene 153 (GADD153) mRNA and
      protein in a time- and concentration-dependent manner. NAC prevented up
      regulation of GADD153 mRNA expression caused by HMDB. These findings suggest that
      HMDB creates an oxidative cellular environment that induces DNA damage and
      GADD153 gene activation, which in turn helps trigger apoptosis in A431 cells.

PMID- 16277401
TI  - Rheological studies utilizing various lots of zein in N,N-dimethylformamide
      solutions.
AB  - Rheological studies were carried out on solutions of zein in N,N
      dimethylformamide (DMF), where the specific lot of zein, concentration, time, and
      temperature were varied. DMF is a good solvent for zein, giving clear, relatively
      low viscosity solutions. It was found that all of the zein solutions behaved in a
      non-Newtonian fashion. At high concentration and elevated temperature, zein
      solutions will increase in viscosity with time. A temperature study on the rate
      of viscosity rise illustrated that at temperatures above 40 degrees C, the rate
      of viscosity rise increased in a non-Arrhenius fashion. There can be significant
      lot to lot variations in commercially obtained zein that gives rise to
      differences in viscosity and rate of viscosity rises. With the samples studied,
      viscosity was found to double from one lot of zein to another. Size exclusion
      chromatography suggests that compositional differences between the lots drive the
      observed differences in viscosity.

PMID- 16277402
TI  - Effect of annealing temperature on gelatinization of rice starch suspension as
      studied by rheological and thermal measurements.
AB  - The effect of annealing temperature (Ta) on the rheological behavior of 10 wt %
      rice starch suspension was investigated by the dynamic viscoelasticity, the
      differential scanning calorimetry (DSC), and the amount of leached out amylose
      and the swelling ratio of starch suspension. The rheological behaviors of the
      annealed samples are classified into three types in terms of Ta: Ta1, 48 and 55
      degrees C, which are much lower than the gelatinization temperature, Tgel (=62
      degrees C); Ta2, 58, 60, and 62 degrees C, which are almost the same as Tgel; and
      Ta3, 65, 68, 70, and 73 degrees C, which are much higher than Tgel. For the
      samples annealed at Ta2, the onset temperature of the storage and the loss
      moduli, G' and G'', increased with increasing T(a), and G' and G" in the
      temperature range from 65 to 90 degrees C gradually increased though smaller than
      those for the nonannealed sample, the control. This can be understood by the
      partial gelatinization; i.e., the leached out amylose prevents further amylose
      from leaching out. The rheological property of the samples annealed at Ta1 is not
      so different from that of the control, and the samples annealed at Ta3 are almost
      gelatinized. The rheological behavior of starch suspension can be controlled by
      Ta.

PMID- 16277403
TI  - Conjugated linoleic acid content and organoleptic attributes of fermented milk
      products produced with probiotic bacteria.
AB  - The effect of probiotic bacteria on the formation of conjugated linoleic acid
      (CLA), microbial growth, and organoleptic attributes (acidity, texture, and
      flavor) of fermented milk products was determined. Four probiotic bacteria,
      Lactobacillus rhamnosus, Propionibacterium freudenreichii subsp. shermanii 56, P.
      freudenreichii subsp. shermanii 51, and P. freudenreichii subsp. freudenreichii
      23, were evaluated individually or in coculture with traditional yogurt cultures
      (Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus salivarius subsp.
      thermophilus). The lipid source was hydrolyzed soy oil. L. rhamnosus, in
      coculture with yogurt culture, resulted in the highest content of CLA. Growth and
      CLA formation of propionibacteria were enhanced in the presence of yogurt
      cultures. Texture and flavor attributes of fermented milks produced with
      propionibacteria were significantly different than the fermented milks processed
      with yogurt cultures. The fermented milks processed with probiotic bacteria in
      coculture with yogurt cultures demonstrated similar acidity, texture, and flavor
      as the fermented milk produced with yogurt cultures.

PMID- 16277404
TI  - Use of differential scanning calorimetry to study lipid oxidation. 1. Oxidative
      stability of lecithin and linolenic acid.
AB  - The oxidation of linolenic acid (LNA) and soy lecithin was studied by
      differential scanning calorimetry (DSC) with linear programmed heating rates (non
      isothermal mode). The interpretation of the shape of DSC curves is discussed, and
      it has been concluded that temperatures of the extrapolated start of heat release
      are the most reliable data for the rapid estimation of the oxidative stability of
      lipid materials. The Ozawa-Flynn-Wall method was used to calculate the kinetic
      parameters of the process: for LNA autoxidation the activation energy, Ea, and
      pre-exponential factor, Z, are 66 +/- 4 kJ/mol and 1.5 x 10(7) s(-1),
      respectively, and the autoxidation of lecithin is described by Ea = 98 +/- 6
      kJ/mol and Z = 9.1 x 10(10) s(-1). Values of Ea and Z can be applied for
      calculation of the overall first-order rate constant of autoxidation at various
      temperatures, k(T). For the two studied lipids the comparison of k(T) values
      shows the inversion of their oxidative stabilities; that is, below 167 degrees C
      lecithin is more stable than LNA, k(T)lecithin < k(T)LNA, and above that
      temperature (termed the isokinetic temperature) k(T)lecithin > k(T)LNA. The
      calculated inversion of oxidative stabilities can be an explanation of similar
      observations for other pairs of lipids if the results of accelerated tests
      measured at temperatures above 100 degrees C are compared with the results
      obtained at temperatures below 100 degrees C.

PMID- 16277405
TI  - Assessment of initial stages of Maillard reaction in dehydrated onion and garlic
      samples.
AB  - The initial steps of the Maillard reaction in freshly laboratory-freeze-dried and
      commercial dehydrated onion and garlic samples have been assessed by quantitative
      determination of 2-furoylmethylamino acids, obtained after acid hydrolysis of the
      corresponding Amadori compound. In freshly prepared samples, hardly any presence
      of 2-furoylmethylamino acids was detected, whereas in commercial samples, onion
      contained much more important levels of 2-furoylmethylamino acids as compared to
      garlic species. 2-Furoylmethyl-gamma-aminobutyric acid (1), 2-furoylmethyl-lysine
      (furosine; 2), and 2-furoylmethylarginine (3) were identified in all commercial
      dehydrated onion samples, with compound 3 being the most abundant. All garlic
      samples presented slightly higher levels of 2 than 3 with no presence of 1. The
      observed differences between onion and garlic commercial samples may be due to
      their very different content of reducing sugars. Moreover, some variations found
      in 2-furoylmethyl derivatives within both onion and garlic species could be also
      attributed to different processing and storage conditions during the manufacture
      of these products. The findings of this study show the first evidence of
      important levels of Amadori compounds in dehydrated garlic and onion samples, as
      well as the usefulness of 2-furoylmethyl derivatives as quality indicators for
      the early detection of the Maillard reaction in onion and garlic products.

PMID- 16277406
TI  - Anthocyanins accumulation and related gene expression in red orange fruit induced
      by low temperature storage.
AB  - The aim of this work was to study the impact of moderately long storage periods
      at 4 degrees C upon red orange [Citrus sinensis (L.) Osbeck] anthocyanins
      production and the expression of structural genes involved in their biosynthesis
      such as phehylalanine ammonia lyase (PAL), chalcone synthase (CHS),
      dihydroflavonol 4-reductase (DFR), and UDP-glucose flavonoid glucosyl transferase
      (UFGT). Our results showed that low temperature-induced anthocyanins accumulation
      in red orange juice vesicles after 75 days reached values eight times higher than
      those kept at 25 degrees C. Furthermore, real-time polymerase chain reaction
      showed that expression of PAL, CHS, DFR, and UFGT was strongly induced during low
      temperature exposure since levels of all transcripts increased at least 40-fold
      with respect to control samples. Interestingly, in orange fruits subjected to a
      brief exposure at low temperature (45 days) and subsequently kept at 25 degrees
      C, the anthocyanins content dropped although samples still maintained higher
      levels of these pigments than those registered in control oranges. Concordantly,
      the expression of chs, dfr, and ufgt declined upon return to control conditions,
      but it was always much higher in samples subjected to brief cold induction than
      in the control samples. On the contrary, the amount of PAL transcripts became
      negligible immediately after the temperature change from 4 to 25 degrees C, thus
      indicating that "early" and "late" genes, respectively, implicated in the first
      and in the last steps leading to the anthocyanins, might be affected by different
      regulation mechanisms.

PMID- 16277407
TI  - Kinetics of formation and functional properties of conjugates prepared by dry
      state incubation of beta-lactoglobulin/acacia gum electrostatic complexes.
AB  - The formation of conjugates between beta-lactoglobulin and acacia gum based on
      electrostatic complexes formed at pH 4.2 was investigated upon dry-state
      incubation for up to 14 days at 60 degrees C and 79% relative humidity (RH). By
      means of SEC-HPLC and RP-HPLC, it was shown that the beta-lactoglobulin incubated
      alone was able to form polymers with molecular masses higher than 200 kDa until
      50% of the initial monomeric protein disappeared after 14 days. In the presence
      of acacia gum at initial protein to polysaccharide weight mixing ratios of 2:1
      and 1:2, only 35% of the initial beta-lactoglobulin monomers disappeared after 14
      days. Using RP-HPLC, an apparent reaction order of 2 was found for the
      disappearance of monomeric beta-lactoglobulin both in the presence or absence of
      acacia gum. However, the reaction rate was faster in the absence of acacia gum.
      SDS-PAGE electrophoresis with silver staining confirmed the formation of beta
      lactoglobulin/acacia gum conjugates. The solubility curves of the incubated beta
      lactoglobulin showed a minimum around pH 4-5. By contrast, the minimum of
      solubility of the beta-lactoglobulin/acacia gum incubated mixtures shifted to
      lower pH values compared to initial mixtures. The conjugates exhibited higher
      foam capacity than the incubated protein as well as lower equilibrium air/water
      surface tension. Conjugation at ratio 1:2 led to increased interfacial viscosity
      (300 mN s m(-1) at 0.01 Hz) compared to beta-lactoglobulin alone (100 mN s m(-1)
      at 0.01 Hz), but similar interfacial elasticity (30-40 mN m(-1)). The foam
      capacity of the conjugates was significantly higher than that of the incubated
      beta-lactoglobulin as well as foam expansion and drainage time, especially at pH
      5.3, i.e., higher than the pH of formation of the conjugates.

PMID- 16277408
TI  - Free amino acid and cysteine sulfoxide composition of 11 garlic (Allium sativum
      L.) cultivars by gas chromatography with flame ionization and mass selective
      detection.
AB  - Two garlic subspecies (n = 11), Allium sativum L. var. opioscorodon (hardneck)
      and Allium sativum L. var. sativum (softneck), were evaluated for their free
      amino acid composition. The free amino acid content of garlic samples analyzed
      ranged from 1121.7 to 3106.1 mg/100 g of fresh weight (mean = 2130.7 +/- 681.5
      mg/100 g). Hardneck garlic had greater methiin, alliin, and total free amino
      acids contents compared to softneck garlic. The major free amino acid present in
      all but one subspecies was glutamine (cv. Mother of Pearl had aspartic acid as
      the major free amino acid). Cv. Music Pink garlic (a rocambole hardneck variety)
      contained the most methiin, alliin, and total free amino acids. The solid-phase
      extraction, alkylchloroformate derivatization, GC-FID, and GC-MS methods used in
      this study were simple and rapid, allowing 18 free amino acids in garlic to be
      separated within 10 min.

PMID- 16277409
TI  - Effect of selenium fertilizer on free amino acid composition of broccoli
      (Brassica oleracea Cv. Majestic) determined by gas chromatography with flame
      ionization and mass selective detection.
AB  - Selenium-enriched broccoli florets, harvested from plants grown on soil
      fertilized with four levels of sodium selenate, were evaluated for their free
      amino acid composition using alkylchlorformate derivatization, solid-phase
      extraction, and GC-FID or GC-MS. The selenium-enriched florets contained 0.4
      (control), 5.7 (treatment A), 98.6 (treatment B), and 879.2 (treatment C)
      microg/g Se (dry weight). Twenty-one free amino acids were identified in the
      control and all three treatments. The total free amino acid content of the
      broccoli florets ranged from 178 mmol/kg (dry weight), for the control, to 479
      mmol/kg (dry weight), for treatment C. Broccoli from treatment C contained the
      highest level of Se, had the most total free amino acids, and had an extremely
      high level of glutamine (Gln) when compared to the control and the other two
      treatments. In general, the smallest addition of Se to the soil (treatment A)
      induced increased levels of all detectable amino acids when compared to the
      control, whereas increased additions of Se (treatments B and C) produced mixed
      responses. Florets from treatment A contained the highest essential amino acid
      content.

PMID- 16277410
TI  - Evaluation of nonstarch polysaccharides and oligosaccharide content of different
      soybean varieties (Glycine max) by near-infrared spectroscopy and proteomics.
AB  - A total of 832 samples of soybeans were screened by near-infrared (NIR)
      reflectance spectroscopy, to identify soybean samples with a lower content of
      oligosaccharides and nonstarch polysaccharides (NSP). Of these, 38 samples were
      identified on the basis of variation in protein content and agronomic value and
      submitted to high-resolution NIR spectroscopy. On the basis of the NIR data, 12
      samples were further selected for chromatographic characterization of
      carbohydrate composition (mono-, di-, and oligosaccharides and NSP). Their
      soluble proteins were separated by two-dimensional gel electrophoresis (2DE).
      Using partial least-squares regression (PLSR), it was possible to predict the
      content of total NSP from the high-resolution NIR spectra, suggesting that NIR is
      a suitable and rapid nondestructive method to determine carbohydrate composition
      in soybeans. The 2DE analyses showed varying intensities of several proteins,
      including the glycinin G1 precursor. PLSR analysis showed a negative correlation
      between this protein and insoluble NSP and total uronic acid (UA).

PMID- 16277411
TI  - Colorimetric evaluation of phenolic content and GC-MS characterization of
      phenolic composition of alimentary and cosmetic argan oil and press cake.
AB  - The global phenolic content of argan oil and press cake samples (alimentary and
      cosmetic) was evaluated using the Folin-Ciocalteu colorimetric method and the
      phenolic composition of argan oil (alimentary and cosmetic) and press cake
      (alimentary) samples were analyzed by GC-MS after extraction with 80:20 (v/v)
      methanol:water and silylation. Identification of chromatographic peaks was made
      by mass selective detection. Nineteen simple phenols were detected, 16 in press
      cake, 6 in the alimentary oil, and 7 in the cosmetic oil, among which 15
      compounds [3-hydroxypyridine (3-pyridinol), 6-methyl-3-hydroxypyridine, catechol,
      resorcinol, 4-hydroxybenzyl alcohol, vanillin, 4-hydroxyphenylacetic acid,
      vanillyl alcohol, 3,4-dihydroxybenzyl alcohol, 4-hydroxy-3-methoxyphenethyl
      alcohol, methyl 3,4-dihydroxybenzoate, hydroxytyrosol, protocatechuic acid,
      epicatechin, and catechin] were identified for the first time in such materials.

PMID- 16277412
TI  - Influence of two fertilization regimens on the amounts of organic acids and
      phenolic compounds of tronchuda cabbage (Brassica oleracea L. Var. costata DC).
AB  - A phytochemical study was undertaken on tronchuda cabbage (Brassica oleracea L.
      var. costata DC) cultivated under conventional and organic practices and
      collected at different times. Six organic acids (aconitic, citric, ascorbic,
      malic, shikimic, and fumaric acids) were identified and quantified by HPLC-UV.
      Qualitative and quantitative differences were noted between internal and external
      leaves. Analysis of the phenolics of the internal leaves was achieved by HPLC
      DAD, and the phenolic profile obtained was revealed to be distinct from that of
      the external leaves. By this means were identified and quantified 11 compounds: 3
      p-coumaroylquinic acid, kaempferol 3-O-sophoroside-7-O-glucoside, kaempferol 3-O
      (caffeoyl)sophoroside-7-O-glucoside, kaempferol 3-O-(sinapoyl)sophoroside-7-O
      glucoside, kaempferol 3-O-(feruloyl)sophoroside-7-O-glucoside, kaempferol 3-O
      sophoroside, two isomeric forms of 1,2-disinapoylgentiobiose, 1-sinapoyl-2
      feruloylgentiobiose, 1,2,2'-trisinapoylgentiobiose, and 1,2'-disinapoyl-2
      feruloylgentiobiose. In general, internal leaves exhibited more constant chemical
      profiles.

PMID- 16277413
TI  - Induction of resistance to gray mold with benzothiadiazole modifies amino acid
      profile and increases proanthocyanidins in grape: primary versus secondary
      metabolism.
AB  - Field treatments of grapevine (cv. Merlot) with the plant activator
      benzothiadiazole (BTH, 0.3 mM) induced resistance against gray mold caused by
      Botrytis cinerea. Both incidence and severity of the disease were reduced. The
      resistance was associated with an increase of total polyphenols in berry skins,
      in particular, the proanthocyanidin fraction, that increased up to 36%. The amino
      acid profile of leaves was also modified by treatments, particularly lysine, that
      augmented 4-fold. Other amino acids involved in resistance mechanisms to either
      biotic or abiotic stress increased as well. These results indicate that BTH
      treatments can be used to control gray mold, thereby limiting an excessive use of
      fungicides, and could be exploited to increase the content of micronutrients of
      high nutritional value, arising from both primary and secondary metabolisms.

PMID- 16277414
TI  - Aminoparathion: a highly reactive metabolite of parathion. 1. Reactions with
      polyphenols and polyphenol oxidase.
AB  - Spiking of tomato and apple fruits with parathion at different levels of about 1
      4 mg/kg irradiation and under simulated sunlight conditions resulted in nearly
      complete photodegradation within 13 h, but extractable parathion degradation
      products could not be found in any case. However, after irradiation of an
      unrealistically spiked apple (134 mg/kg) different photoproducts including
      aminoparathion (AP) were detectable by HPLC, proving that the hitherto postulated
      photochemistry of parathion indeed takes place in the fruit cuticle environment.
      Besides the photoreduction pathway it was shown for the first time that AP is
      also easily formed by reduction of the primary photoproduct nitrosoparathion with
      thiols (cysteine, glutathione), while ascorbic acid only leaves
      hydroxylaminoparathion. In the presence of polyphenols, AP was effectively bound
      to quinone intermediates formed by both silver oxide and polyphenol oxidases. For
      pyrocatechol, a disubstituted o-quinone derivative could be isolated as a dark
      red addition product and structurally be elucidated. However, in the presence of
      caffeic acid, catechol, naringin, and quercetin, respectively, insoluble dark
      colored polymers precipitated within 48 h, while in the supernatants AP was not
      detectable any more. Polymer-bound and nonextractable AP was proven by
      transesterification with sodium ethoxide releasing O,O,O-triethyl thiophosphate
      which was determined by GC. Additionally, AP itself was a substrate for
      polyphenol oxidases, resulting in a quinone imine intermediate which in turn
      reacted with excessive AP yielding deep red colored di- and trimerization
      products.

PMID- 16277415
TI  - Pesticide sorption and diffusion in natural clay loam aggregates.
AB  - Pesticide sorption in soils is controlled by time-dependent processes such as
      diffusion into soil aggregates and microscopic sorbent particles. This study
      examines the rate-controlling step for time-dependent sorption in clay loam
      aggregates. Aggregates (5 mm) were stabilized with alginate, and adsorption of
      azoxystrobin, chlorotoluron, and cyanazine was measured in batch systems
      equilibrated for periods between 1 h and 7 days. Stepwise desorption was measured
      at 1- or 3-day intervals following 1 or 7 days of adsorption. Time-dependent
      adsorption was also measured on dispersed soil. Results were interpreted using
      process-based modeling. Adsorption on dispersed soil was described by
      intraparticle sorption and diffusion. Adsorption in the aggregates was much less
      than in suspension, suggesting that part of the sorption capacity of the
      dispersed soil was not available within the aggregates (approximately 50%).
      Adsorption and desorption were reversible and could be described by pore
      diffusion into the aggregate with effective diffusion coefficients between 0.5 x
      10(-10) and 1 x 10(-10) m2 s(-1), a factor 3-6 slower than estimated
      theoretically. Intraparticle diffusion did not seem to contribute to sorption in
      the aggregates at this time scale. Apparent hysteresis was explained by
      nonattainment of equilibrium during the adsorption and desorption steps.

PMID- 16277416
TI  - Phytoremediation of metolachlor by transgenic rice plants expressing human
      CYP2B6.
AB  - We introduced the human cytochrome P450 gene CYP2B6 into rice plants (Oryza
      sativa L. cv. Nipponbare), and the CYP2B6-expressing rice plants became more
      tolerant to various herbicides than nontransgenic Nipponbare rice plants. In
      particular, CYP2B6 rice plants grown in soil showed tolerance to the
      chloroacetanilide herbicides alachlor and metolachlor. We evaluated the
      degradation of metolachlor by CYP2B6 rice plants to confirm the metabolic
      activity of the introduced CYP2B6. Although both CYP2B6 and nontransgenic
      Nipponbare rice plants could decrease the amount of metolachlor in plant tissue
      and culture medium, CYP2B6 rice plants could remove much greater amounts. In a
      greenhouse, the ability of CYP2B6 rice plants to remove metolachlor was confirmed
      in large-scale experiments, in which these plants appeared able to decrease
      residual quantities of metolachlor in water and soil.

PMID- 16277417
TI  - Volatile constituents of Semnostachya menglaensis Tsui.
AB  - Semnostachya menglaensis Tsui (Acanthaceae) is a rare plant indigenous to Mengla
      in the tropical rainforest of the Xishuangbanna prefecture in the south of Yunnan
      province, People's Republic of China. When the leaves are crushed, a
      characteristic smell of basmati rice or pandan leaves develops. Their hexane
      extract, prepared from a specimen growing in a greenhouse of the botanical garden
      of the Kunming Institute of Botany, contains 1-(3,4,5,6-tetrahydro-2-pyridyl)-1
      propanone (41.2%) and 1-(1,4,5,6-tetrahydro-2-pyridyl)-1-propanone (37.5%) which
      constitute the main part of the volatile compounds. Minor components are 1
      (3,4,5,6-tetrahydro-2-pyridyl)-1-ethanone (4.9%), 1-(1,4,5,6-tetrahydro-2
      pyridyl)-1-ethanone (4.8%), 1-(2-piperidyl)-1-propanone (5.2%), 1-octen-3-ol
      (3.2%), 1-octen-3-one (1.9%), and 3-octanol and 1-(2-pyridyl)-1-propanone in
      trace amounts.

PMID- 16277418
TI  - Application of hydrophilic interaction liquid chromatography/comparative taste
      dilution analysis for identification of a bitter inhibitor by a combinatorial
      approach based on Maillard reaction chemistry.
AB  - Activity-directed fractionation of heated carbohydrate/alanine solutions recently
      led to the discovery of (+)-(S)-1-(1-carboxyethyl)-5-hydroxy-2
      (hydroxymethyl)pyridinium inner salt (1, alapyridaine), and it has been shown
      that this compound lowers the detection thresholds of sugars, glutamate, and NaCl
      solutions, whereas no influence on bitter perception was observed. As this class
      of Maillard-derived pyridinium betaines seemed to be promising targets for
      further research on their taste modulatory activity, the objective of the present
      investigation was to screen for bitter taste-suppressing target molecules in
      combinatorial libraries of pyridinium betaines prepared from 5
      (hydroxymethyl)furan-2-aldehyde and amino acid mixtures by use of Maillard-type
      reaction chemistry instead of synthesizing and purifying each derivative
      individually. By application of hydrophilic interaction liquid chromatography in
      combination with the recently developed comparative taste dilution analysis,
      followed by structure determination, synthesis, and sensory studies, we have now
      succeeded in identifying 1-carboxymethyl-5-hydroxy-2-hydroxymethylpyridinium
      inner salt (2) as a potential bitter-suppressing candidate. While tasteless on
      its own, 2 was found to reduce the bitterness of various bitter tastants such as
      the amino acid L-phenylalanine, the peptide Gly-Leu, the alkaloid caffeine, and
      the bitter glycosides salicin and naringin.

PMID- 16277420
TI  - Water activity-temperature state diagram of amorphous lactose.
AB  - Development in the glass transition temperature, Tg, to reach a stabilized value
      for amorphous lactose stored at 5, 25, and 38 degrees C at different water
      activities varying from aw = 0.21 to 0.59 was followed by differential scanning
      calorimetry. Combinations of stabilized Tg and water activity were used for
      interpolation of the value of water activity, where Tg was equal to the storage
      temperature. These values of water activity were used to construct a state
      diagram in the (aw,T)-plane for lactose in the amorphous state from which
      critical combinations of water activity and storage temperature may be obtained
      for optimization of storage conditions of lactose-based dry products.

PMID- 16277419
TI  - Analysis of eight capsaicinoids in peppers and pepper-containing foods by high
      performance liquid chromatography and liquid chromatography-mass spectrometry.
AB  - Diverse procedures have been reported for the isolation and analysis of secondary
      metabolites called capsaicinoids, pungent compounds in the fruit of the Capsicum
      (Solanaceae) plant. To further improve the usefulness of high-performance liquid
      chromatography (HPLC), studies were carried out on the analysis of extracts
      containing up to eight of the following capsaicinoids: capsaicin,
      dihydrocapsaicin, homocapsaicin-I, homocapsaicin-II, homodihydrocapsaicin-I,
      homodihydrocapsaicin-II, nonivamide, and nordihydrocapsaicin. HPLC was optimized
      by defining effects on retention times of (a) the composition of the mobile phase
      (acetonitrile/0.5% formic acid in H2O), (b) the length of the Inertsil column,
      and (c) the capacity values (k) of the column packing. Identification was based
      on retention times and mass spectra of individual peaks. Quantification was based
      on the UV response at 280 nm in HPLC and recoveries from spiked samples. The
      method (limit of detection of approximately 15-30 ng) was successfully used to
      quantify capsaicinoid levels of parts of the pepper fruit (pericarp, placenta,
      seeds, and in the top, middle, and base parts of whole peppers) in 17 species of
      peppers and in 23 pepper-containing foods. The results demonstrate the usefulness
      of the method for the analysis of capsaicinoids ranging from approximately 0.5 to
      3600 microg of capsaicin equiv/g of product. The water content of 12 fresh
      peppers ranged from 80.8 to 92.7%. The described freeze-drying, extraction, and
      analysis methods should be useful for assessing the distribution of capsaicinoids
      in the foods and in defining the roles of these biologically active compounds in
      the plant, the diet, and medicine.

PMID- 16277421
TI  - Inhibition of lipid oxidation in cooked beef patties by hydrolyzed potato protein
      is related to its reducing and radical scavenging ability.
AB  - Protein hydrolysates were prepared by limited alcalase hydrolysis (0.5, 1, and 6
      h, corresponding to degrees of hydrolysis of 0.72, 1.9, and 2.3, respectively) of
      heat-coagulated potato protein. The hydrolysates were characterized for peptide
      composition, ferric reducing/antioxidant power (FRAP), 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging activity, and
      Fe2+- and Cu2+-chelation capacity. Hydrolyzed and intact proteins were formulated
      (4%, w/w) into beef patties to determine in situ antioxidant efficacy.
      Thiobarbituric acid-reactive substances (TBARS) and peroxide value (PV) formed in
      cooked and PVC-packaged patties during storage (4 degrees C, 0-7 days) were
      analyzed. Hydrolysis increased the protein solubility by 14-19-fold and produced
      numerous short peptides (< 6 kDa). The FRAP values of the protein sample (23
      micromol/g) increased markedly after hydrolysis but were similar between the
      three hydrolysates (597-643 micromol/g). Similarly, the ABTS radical-scavenging
      activity also was increased by hydrolysis and was the greatest for the 1-h
      hydrolysate. Hydrolysis increased the Cu2+-chelation activity but decreased the
      Fe2+-chelation ability of the protein. The production of PV in patties after 7
      days of storage was lowered 44.9% and 74.5% (P < 0.05), and that of TBARS was
      reduced 40.9% and 50.3% (P < 0.05), by intact and hydrolyzed proteins,
      respectively.

PMID- 16277422
TI  - Rheological properties of fast skeletal myosin rod and light meromyosin from
      walleye pollack and white croaker: contribution of myosin fragments to thermal
      gel formation.
AB  - Myosin rod and light meromyosin (LMM) of walleye pollack and white croaker were
      examined for their rheological properties by measuring dynamic viscoelastic
      parameters. Rods from walleye pollack and white croaker increased their storage
      moduli (G') in the ranges of 29-43 degrees C and 31-38 degrees C, respectively,
      in temperature sweep analysis. Walleye pollack LMM showed no peak of G' upon
      heating, whereas the white croaker counterpart exhibited a single sharp peak of
      G' at 35 degrees C. Loss modulus (G") showed similar temperature-dependent
      changes for the two fish species as the case of G', irrespective of rod and LMM,
      although G" values were lower than those of G'. Thus, rheological properties of
      rod and LMM were different between walleye pollack and white croaker. Taken
      together with data previously reported for myosin, it was considered that both
      myosin rods from walleye pollack and white croaker are attributed to thermal gel
      formation of myosin in a low-temperature range, though in a species-specific
      manner.

PMID- 16277424
TI  - Characterization of the activity of tyrosinase on betaxanthins derived from (R)
      amino acids.
AB  - The activity of tyrosinase (EC 1.14.18.1) on selected (R)-betaxanthins is
      characterized in depth, demonstrating that the activity of the enzyme is not
      restricted to betaxanthins derived from (S)-amino acids. Conversion of (R)
      tyrosine-betaxanthin [(R)-portulacaxanthin II] to the pigment (R)-dopaxanthin and
      its further oxidation to a series of products is described. Compound identity was
      studied by high performance liquid chromatography and electrospray ionization
      mass spectrometry. The reaction rate on the (R)-isomer of dopaxanthin is 1.9-fold
      lower than that obtained for the (S)-isomer in previous studies. Tyrosinase
      showed stereospecificity in its affinity toward betaxanthins. The
      characterization of the activity of tyrosinase on (R)-betaxanthins reinforces the
      role of the enzyme in the biosynthetic scheme of betalains.

PMID- 16277423
TI  - Thermal oxidation of 9'-cis-neoxanthin in a model system containing peroxyacetic
      acid leads to the potent odorant beta-damascenone.
AB  - The potent odorant beta-damascenone was formed directly from 9'-cis-neoxanthin in
      a model system by peroxyacetic acid oxidation and two-phase thermal degradation
      without the involvement of enzymatic activity. Beta-damascenone formation was
      heavily dependent on pH (optimum at 5.0) and temperature, occurring over the two
      sequential phases. The first was incubation with peroxyacetic acid at 60 degrees
      C for 90 min, and the second was at above 90 degrees C for 20 min. Only traces of
      beta-damascenone were formed on application of only one of the two phases.
      Formate and citrate solutions produced a much better environment for beta
      damascenone formation than acetate and phosphate. About 7 microg/L beta
      damascenone was formed from 5.8 mg/L 9'-cis-neoxanthin under optimal experimental
      condition. The detailed pathway by which beta-damascenone is formed remains to be
      elucidated.

PMID- 16277425
TI  - Cell wall fractions isolated from outer layers of rye grain by sequential
      treatment with alpha-amylase and proteinase: structural investigation of polymers
      in two ryes with contrasting breadmaking quality.
AB  - Recent studies have indicated that some structural features of arabinoxylans, the
      major cell wall polysaccharides, might be potential quality markers in the
      selection of rye breeding materials. To specify the most appropriate
      characteristics, the differences in the structure of cell wall components were
      studied in two ryes with high and low breadmaking qualities. Two cell wall
      fractions were isolated from the outer layers of the grain (pooled shorts and
      bran fractions) by a consecutive water extraction with alpha-amylase (WE-A) and
      proteinase K (WE-P). Polysaccharides predominated in the WE-A fraction
      (approximately 64%, mainly arabinoxylans). By contrast, the WE-P fraction
      contained mostly protein (approximately 63%), and its level of polysaccharides
      was relatively low (approximately 18%). The 1H NMR and sugar analysis of the
      ammonium sulfate precipitated subfractions revealed that the WE-A was built of
      four arabinoxylan populations with marked structural differences (arabinose-to
      xylose ratios, Ara/Xyl, of approximately 0.3, 0.5, 0.8, and 1.2). Instead, the
      arabinoxylans present in the WE-P were generally enriched in disubstituted
      xylopyranosyl residues. The ratio of phenolic components to arabinose residues in
      the WE-P fraction (indicated by 1H NMR) and the proportion of polymers with the
      highest molecular weights in the WE-A fraction (revealed by HPSEC) distinguished
      well two ryes with diverse breadmaking qualities. Much less obvious differences
      between both ryes were observed in the ratio of amide I to amide II band
      intensities of FTIR spectra for the WE-P and in the level of phenolic acids and
      ferulic acid dehydrodimers for both cell wall preparations.

PMID- 16277426
TI  - Oxidation of dietary polyphenolics by hydroperoxidase activity of lipoxygenase.
AB  - Lipoxygenase, in the presence of hydrogen peroxide, produces the oxidative
      decomposition of quercetin, naringenin, and resveratrol, known antioxidant
      molecules. Quercetin was the molecule more efficiently oxidized, followed by
      resveratrol and naringenin. When this molecule was incubated in the presence of
      GSH, a quinoid derivative was produced. This compound was not obtained in the
      presence of naringenin or resveratrol, suggesting that in the presence of
      hydrogen peroxide and lipoxygenase, quercetin may be oxidized to a prooxidant
      species. When hydrogen peroxide was substituted by hydroperoxy linoleic acid, the
      same oxidative process was observed. This means that in food products in which
      lipoxygenase and linoleic acid are presents, quercetin may be oxidized to
      prooxidant species; in contrast, naringenin and resveratrol may constitute a
      valid additive for the prevention of the oxidative degradation of foods.

PMID- 16277427
TI  - Enzyme-aided modification of chicken-breast myofibril proteins: effect of laccase
      and transglutaminase on gelation and thermal stability.
AB  - The effect of laccase and transglutaminase (TG) on cross-linking, gelation, and
      thermal stability of salt-soluble chicken-breast myofibril proteins was
      investigated at pH 6. Both enzymes modified the protein pattern detected by SDS
      PAGE. Identification of proteins by peptide mass mapping showed that myosin heavy
      chain (MHC) and troponin T were the most affected proteins. These proteins faded
      or disappeared as a function of the incubation time with both enzymes on SDS
      PAGE. The molecular weight of actin was not, however, affected by either enzyme.
      The effects that the enzymes had on the gel formation of chicken-breast
      myofibrils were studied in 0.35 and 0.60 M NaCl solutions at 3% protein content
      and a constant temperature of 40 degrees C by using a small deformation
      viscoelastic measurement. TG substantially increased the storage modulus (G') of
      3% protein in 0.35 M NaCl. Without the enzymes, gelation was insignificant in
      0.35 M NaCl. The increased solubility of the proteins at 0.60 M NaCl intensified
      gelation with TG. G' increased 32 and 64% at dosages of 10 and 100 nkat of TG,
      respectively. Also, laccase increased G' of the gel in 0.60 M salt concentration.
      However, a high laccase dosage decreased the magnitude of G' below the control
      level. Differential scanning calorimetric (DSC) measurements indicated slightly
      reduced myosin heat stability after TG pretreatment and increased actin heat
      stability with both enzymes. Maximum transition temperatures did not alter with
      either enzyme.

PMID- 16277428
TI  - Arsenic speciation in farmed Hungarian freshwater fish.
AB  - Arsenic speciation analysis was carried out on freshwater farmed fish collected
      from an area with elevated groundwater arsenic concentrations in Hungary as well
      as from outside of the area (control samples). The arsenic species were
      determined by high-performance liquid chromatography-inductively coupled plasma
      mass spectrometry on methanol extracts of the muscle tissue from the fish.
      Catfish (Claries gariepinus) were raised in geothermal water where the average
      total arsenic concentrations were 167 (contaminated sites) and 15.1 ng As mL(-1)
      (control); they were all fed an artificial diet containing 2880 microg As kg(-1)
      total arsenic, mostly present as arsenobetaine. In the catfish, the accumulated
      total arsenic (2510-4720 microg As kg(-1)) was found mostly in the form of
      arsenobetaine suggesting that uptake of arsenic was dominated by their diet. Carp
      (Cyprinus carpio) were cultured in surface lakes with no significant arsenic
      pollution and had total arsenic concentrations ranging from 62 to 363 microg As
      kg(-1). The arsenic species found in the carp extracts differed markedly from
      those in the catfish in that no arsenobetaine was detected. Most samples of carp
      from the investigated sites contained low concentrations of As(III) (arsenite),
      As(V) (arsenate), MA (methylarsonate), and DMA (dimethylarsinate), and no other
      compounds were detected. The four individuals from the control site, however, all
      contained appreciable levels of oxo-arsenosugar-glycerol and oxo-arsenosugar
      phosphate. Indeed, the oxo-arsenosugar-phosphate dominated the speciation pattern
      for these carp contributing about 75% of the sum of species. The contrast between
      these two freshwater aquaculture species regarding total arsenic and arsenic
      species has relevant toxicological aspects in terms of food safety.

PMID- 16277429
TI  - How cysteine reacts with citral: an unexpected reaction of beta,beta
      disubstituted acroleins with cysteine leading to hexahydro-1,4-thiazepines.
AB  - The reaction of beta,beta-disubstituted acroleins [3-methyl-2-butenal (1), 3
      methyl-2-hexenal (2), and citral (3)] with cysteine gave 1:2 adducts of a novel
      structural type, namely hexahydro-1,4-thiazepines. To the best of our knowledge,
      the spontaneous formation of a seven-membered heterocycle from the addition of
      cysteine to alpha,beta-unsaturated aldehydes is unprecedented. The adduct 6
      obtained from citral, under acidic conditions, reacted further to give the new
      bicyclic compound 8.

PMID- 16277430
TI  - Preliminary study of oaklins, a new class of brick-red catechinpyrylium pigments
      resulting from the reaction between catechin and wood aldehydes.
AB  - Several structurally related pigments were found to result from the reaction
      between catechin and coniferaldehyde/sinapaldehyde extracted from oak wood. Their
      structures were tentatively identified by mass spectrometry, and their formation
      was studied in different pH and temperature conditions for several days. They
      were all found to have a characteristic catechinpyrylium core, thereby
      constituting a new class of compounds named as oaklins. One of the main oaklins
      was also detected in a commercial table red wine aged in oak barrels.

PMID- 16277431
TI  - Structural stability and prebiotic properties of resistant starch type 3 increase
      bile acid turnover and lower secondary bile acid formation.
AB  - Microbial metabolism is essential in maintaining a healthy mucosa in the large
      bowel, preferentially through butyrate specific mechanisms. This system depends
      on starch supply. Two structurally different resistant starches type 3 (RS3) have
      been investigated with respect to their resistance to digestion, fermentability,
      and their effects on the composition and turnover of bile acids in rats. RSA (a
      mixture of retrograded maltodextrins and branched high molecular weight
      polymers), which is more resistant than RSB (a retrograded potato starch),
      increased the rate of fermentation accompanied by a decrease of pH in cecum,
      colon, and feces. Because they were bound to RS3, less bile acids were
      reabsorbed, resulting in a higher turnover through the large bowel. Because of
      the rise of volume, the bile acid level was unchanged and the formation of
      secondary bile acids was partly suppressed. The results proved a strong relation
      between RS3, short chain fatty acid production, and microflora. However, butyrate
      specific benefits are only achieved by an intake of RS3 that result in good
      fermentation properties, which depend on the kind of the resistant starch
      structures.

PMID- 16277432
TI  - Relative inhibition of lipid peroxidation, cyclooxygenase enzymes, and human
      tumor cell proliferation by natural food colors.
AB  - The most abundant water soluble natural food colors are betacyanins and
      anthocyanins. Similarly, lycopene, bixin, beta-carotene, and chlorophyll are
      water insoluble colors. Pure betanin, bixin, lycopene, chlorophyll, beta
      carotene, and cyanidin-3-O-glucoside were isolated from Beta vulgaris, Bixa
      orellana,Lycopersicum esculentum, Spinacia oleracea, Daucus carrota, and Prunus
      cerasus, respectively. These natural pigments, alone and in combination, were
      evaluated for their relative potencies against cyclooxygenase enzymes and tumor
      cell growth inhibition by using MCF-7 (breast), HCT-116 (colon), AGS (stomach),
      CNS (central nervous system), and NCI-H460 (lung) tumor cell lines. Among the
      colors tested, betanin, cyanidin-3-O-glucoside, lycopene, and beta-carotene
      inhibited lipid peroxidation. However, all pigments tested gave COX-1 and COX-2
      inhibition and showed a dose-dependent growth inhibition against breast, colon,
      stomach, central nervous system, and lung tumor cells, respectively. The mixtures
      of these pigments were also evaluated for their synergistic effects and chemical
      interactions at various concentrations. The mixture of anthocyanin and betanin
      negated their efficacy in the cell growth inhibitory assay and did not enhance
      the COX enzyme inhibitory activity. This is the first report of a comparative
      evaluation and the impact on biological activities of these pigments alone and in
      combination.

PMID- 16277433
TI  - Aflatoxin production in six peanut (Arachis hypogaea L.) genotypes infected with
      Aspergillus flavus and Aspergillus parasiticus, isolated from peanut production
      areas of Cordoba, Argentina.
AB  - Aflatoxin contamination is one of the main factors affecting peanut seed quality.
      One of the strategies to decrease the risk of peanut aflatoxin contamination is
      the use of genotypes with resistance to Aspergillus infection. This laboratory
      study reports the resistance to Aspergillus infection and aflatoxin contamination
      of six peanut genotypes inoculated with 21 Aspergillus isolates obtained from the
      peanut production region of Cordoba, Argentina. The resistance was investigated
      in the seed coat and cotyledons of three resistant genotypes (J11, PI 337394, and
      PI 337409) and three breeding lines (Manfredi 68, Colorado Irradiado, and Florman
      INTA) developed at the Instituto Nacional de Tecnologia Agropecuaria (INTA),
      Manfredi Experimental Station, Cordoba, Argentina. Resistance to fungal
      colonization and aflatoxin contamination was found to be associated with seed
      coat integrity in the PI 337394, PI 337409, and J11 genotypes, whereas the INTA
      breeding lines such as Colorado Irradiado showed a moderate resistance and the
      Manfredi 68 and Florman INTA genotypes the least resistance. Furthermore, another
      type of resistance associated with cotyledons was found only in the PI 337394
      genotype.

PMID- 16277434
TI  - Fusarium graminearum TRI14 is required for high virulence and DON production on
      wheat but not for DON synthesis in vitro.
AB  - Fusarium head blight (FHB) of wheat (Triticum aestivum L.), caused by the fungus
      Fusarium graminearum, is a major concern worldwide. FHB grain is reduced in
      yield, may fail to germinate, and is often contaminated with deoxynivalenol, a
      trichothecene mycotoxin linked to a variety of animal diseases and feed refusals.
      Annual losses in the tens of millions of dollars due to FHB underscore the need
      to develop improved methods of disease control and prevention. Previous research
      has identified deoxynivalenol biosynthesis as a virulence factor on wheat.
      Recently, we found that the TRI14 gene of F. sporotrichioides, closely related to
      F. graminearum, was not required for synthesis of a related trichothecene, T-2
      toxin. TRI14 does not share similarity with any previously described genes in the
      databases. In this study, we examined the role that F. graminearum TRI14 may play
      in both deoxynivalenol synthesis and in virulence on wheat. TRI14 deletion
      mutants synthesize deoxynivalenol on cracked maize kernel medium and exhibit wild
      type colony morphology and growth rate on complex and minimal agar media.
      However, FHB assays on greenhouse-grown wheat indicate that FgDeltaTri14 mutants
      cause 50-80% less disease than wild type and do not produce a detectable quantity
      of deoxynivalenol on plants. We discuss a number of possible roles that TRI14 may
      play in the disease process.

PMID- 16277435
TI  - Residue depletion of eprinomectin in bovine tissues after subcutaneous
      administration.
AB  - A study of the tissue depletion of eprinomectin (EPR) subcutaneously administered
      to cattle at a dose of 500 mg per kg of body weight was carried out. EPR
      concentrations were determined in muscle, liver, kidney, and fat. Twenty-four
      parasite-free cross cattle were treated with the EPR injectable oil formulation.
      Three treated animals (two males and one female) were selected randomly to be
      sacrificed at 1, 3, 7, 14, 21, 28, 42, and 56 days withdrawal after injection.
      EPR residue concentrations were determined using HPLC with fluorescence
      detection. Muscle samples showed the lowest EPR concentrations throughout the
      study period. The highest EPR concentrations at all sampling times were measured
      in liver tissue, indicating that liver is a target tissue for EPR. EPR
      concentrations in all of the tissues analyzed were below the accepted maximum
      residue limits recommended by the European Union at 8 days posttreatment.

PMID- 16277436
TI  - Do fumonisin mycotoxins occur in wheat?
AB  - The fumonisin mycotoxins are mainly produced by the fungi Fusarium
      verticillioides and Fusarium proliferatum, which are both field pathogens of
      maize. The natural occurrence of fumonisins has been verified in maize and a
      large range of maize-based products in many countries of the world. However,
      occasional reports have emerged of fumonisins being detected in wheat, despite
      the main producing fungi not being pathogens of this cereal. An investigation was
      conducted into a recent report of the natural occurrence of fumonisins in the
      2003/2004 South African wheat crop at levels up to 1.7 mg/kg, as determined by
      immunoaffinity column cleanup and direct fluorometric measurement. An AOAC
      International high-performance liquid chromatographic (HPLC) method for the
      determination of fumonisins in maize was modified and validated for the
      determination of fumonisins in spiked wheat samples. HPLC analysis of the wheat
      samples previously found to be positive for fumonisins revealed no detectable (<5
      microg/kg) fumonisins in the 30 samples analyzed. These results, which lay doubt
      on previous reports of fumonisins in wheat, emphasize the fact that screening
      methods, especially if used outside their range or matrix of applicability, can
      produce false positive results despite the use of immunoaffinity cleanup. Such
      results should be validated and confirmed with a more definitive technique.

PMID- 16277437
TI  - Effects of separate carrier generation on the emission properties of InAs/GaAs
      quantum dots.
AB  - Individual quantum dots have been studied by means of microphotoluminescence with
      dual-laser excitation. The additional infrared laser influences the dot charge
      configuration and increases the dot luminescence intensity. This is explained in
      terms of separate generation of excess electrons and holes into the dot from the
      two lasers. With increasing dot density and/or sample temperature, the increase
      of the luminescence intensity vanishes progressively, while the possibility to
      control the dot charge remains.

PMID- 16277438
TI  - Silver/dendrimer nanocomposites as biomarkers: fabrication, characterization, in
      vitro toxicity, and intracellular detection.
AB  - We have synthesized water-soluble, biocompatible, fluorescent, and stable
      silver/dendrimer nanocomposites that exhibit a potential for in vitro cell
      labeling. Amino-, hydroxyl-, and carboxyl-terminated ethylenediamine core
      generation 5 poly(amidoamine) dendrimers were utilized to prepare aqueous
      silver(I)-dendrimer complexes (with the molar ratio of 25 Ag+ per dendrimer) at
      the biologic pH of 7.4. Conversion of silver(I)-dendrimer complexes into
      dendrimer nanocomposites was achieved by irradiating the solutions with UV light
      to reduce the bound Ag+ cations to zerovalent Ag0 atoms, which were
      simultaneously trapped in the dendrimer network, resulting in the formation of
      {(Ag0)25-PAMAM_E5.NH2}, {(Ag0)25-PAMAM_E5.NGly}, and {(Ag0)25-PAMAM_E5.NSAH}
      dendrimer nanocomposites (DNC), respectively. The silver-DNCs were characterized
      by means of UV-vis, fluorescence spectroscopy, dynamic light-scattering, zeta
      potential measurements, high-resolution transmission electron microscopy, X-ray
      energy dispersive spectroscopy, and selected area electron diffraction. The
      cytotoxicity of dendrimers and related silver nanocomposites was evaluated using
      an XTT colorimetric assay of cellular viability. The cellular uptake of
      nanoparticles was examined by transmission electron and confocal microscopy.
      Results indicate that {(Ag0)25-PAMAM_E5.NH2}, {(Ag0-)25-PAMAM_E5.NGly}, and
      {(Ag0)25-PAMAM_E5.NSAH} form primarily single particles with diameters between 3
      and 7 nm. The dendrimer nanocomposites are fluorescent, and their surface charge,
      cellular internalization, toxicity, and cell labeling capabilities are determined
      by the surface functionalities of dendrimer templates. The {(Ag0)25-PAMAM_E5.NH2}
      and {(Ag0)25-PAMAM_E5.NSAH} nanocomposites exhibit potential application as cell
      biomarkers.

PMID- 16277439
TI  - Novel carbon nanotube-polystyrene foam composites for electromagnetic
      interference shielding.
AB  - A novel carbon nanotube-polystyrene foam composite has been fabricated
      successfully. The electromagnetic interference (EMI) shielding effectiveness
      measurements indicated that such foam composites can be used as very effective,
      lightweight shielding materials. The correlation between the shielding
      effectiveness and electrical conductivity and the EMI shielding mechanism of such
      foam composites are also discussed.

PMID- 16277440
TI  - Achieving high-current carbon nanotube emitters.
AB  - When a carbon nanotube emitter is operated at high currents (typically above 1
      microA per emitter), a small voltage drop ( approximately few volts) along its
      length or at its contact generates a reverse/canceling electric field that causes
      a saturation-like deviation from the classical Fowler-Nordheim behavior with
      respect to the applied electric field. We present a correction to the Fowler
      Nordheim equation to account for this effect, which is experimentally verified
      using field emission and contact electrical measurements on individual carbon
      nanotube emitters. By using rapid thermal annealing to improve both the
      crystallinity of the carbon nanotubes and their electrical contact to the
      substrate, it is possible to reduce this voltage drop, allowing very high
      currents of up to 100 microA to be achieved per emitter with no significant
      deviation from the classical Fowler-Nordheim behavior.

PMID- 16277441
TI  - Use of phosphine as an n-type dopant source for vapor-liquid-solid growth of
      silicon nanowires.
AB  - Phosphine (PH3) was investigated as an n-type dopant source for Au-catalyzed
      vapor-liquid-solid (VLS) growth of phosphorus-doped silicon nanowires (SiNWs).
      Transmission electron microscopy characterization revealed that the as-grown
      SiNWs were predominately single crystal even at high phosphorus concentrations.
      Four-point resistance and gate-dependent conductance measurements confirmed that
      electrically active phosphorus was incorporated into the SiNWs during VLS growth.
      A transition was observed from p-type conduction for nominally undoped SiNWs to n
      type conduction upon the introduction of PH3 to the inlet gas. The resistivity of
      the n-type SiNWs decreased by approximately 3 orders of magnitude as the inlet
      PH3 to silane (SiH4) gas ratio was increased from 2 x 10(-5) to 2 x 10(-3). These
      results demonstrate that PH3 can be used to produce n-type SiNWs with properties
      that are suitable for electronic and optoelectronic device applications.

PMID- 16277442
TI  - Creating focused plasmons by noncollinear phasematching on functional gratings.
AB  - We report on the concept, generation, and first observations of focused surface
      plasmons on shaped gratings. The grating patterns are designed to realize
      focusing and directing through noncollinear phasematching. The plasmons are
      generated on patterned gold surfaces, and the plasmon propagation is observed
      using phase-sensitive photon scanning tunneling microscopy (PSTM) to extract the
      propagation pattern, direction, and wavelength.

PMID- 16277443
TI  - Synthesis of flexible magnetic nanowires of permanently linked core-shell
      magnetic beads tethered to a glass surface patterned by microcontact printing.
AB  - We have developed an efficient, one-step method to create magnetic nanowires
      consisting of permanently linked chains of magnetic beads of varying flexibility
      tethered to a patterned glass surface using simple amidation chemistry. The
      flexibility of the nanowire was governed by the molecular weight of the molecule
      used to covalently link the beads and its length by the height of the
      microchannel in which it was synthesized. The nanowire diameter was determined
      both by the bead size and by the number of beads adhering to each dot in the
      microstamped, patterned array. Longer nanowires can form loops attached at two
      points on the glass surface. Both single flexible chains and flexible loops can
      adopt different configurations (straight, hairpin, S-shaped, etc.) when subjected
      to magnetic fields, the configurations depending on the directions of these
      fields. Shorter, less flexible nanowires align with the field always and do not
      exhibit the more exotic configurations seen for long, flexible chains and loops.
      These magnetic nanowires can have potential use in microfluidic pumping and
      mixing processes and in microparticle manipulation.

PMID- 16277444
TI  - Predicting the thermal resistance of nanosized constrictions.
AB  - Various devices and technologies using nanowires and nanoparticles are under
      intense investigation because of their promise. In these devices, nanowires or
      nanoparticles are typically in contact with another surface. The contact between
      a nanowire and a nanoparticle with a substrate forms a constriction of the order
      of a few nanometers. A continuum description of heat transport at these nanosized
      constrictions will break down. In this paper, an analytical model is presented in
      which the relevant length scales have been taken into consideration. The results
      show that the constriction resistance of nanoconstrictions is much higher than
      those predicted using macroscopic approaches. The Knudsen number is the key
      parameter for constriction formed between the same materials, whereas the
      microscopic Biot number based on phonon thermal boundary resistance is the key
      parameter for constriction formed between dissimilar materials. Finally, the
      model is applied to calculate the thermal resistance of the nanowire/planar
      interface.

PMID- 16277445
TI  - Photothermal absorption spectroscopy of individual semiconductor nanocrystals.
AB  - Photothermal heterodyne detection is used to record the first room-temperature
      absorption spectra of single CdSe/ZnS semiconductor nanocrystals. These spectra
      are recorded in the high cw excitation regime, and the observed bands are
      assigned to transitions involving biexciton and trion states. Comparison with the
      single nanocrystals photoluminescence spectra leads to the measurement of
      spectral Stokes shifts free from ensemble averaging.

PMID- 16277446
TI  - Controlled synthesis of hyperbranched inorganic nanocrystals with rich three
      dimensional structures.
AB  - Controlled synthesis of hyperbranched CdTe and CdSe semiconductor nanocrystals is
      presented. The length of the arms and the degree of branching could be controlled
      independently by varying the amount and kind of organic surfactant. The three
      dimensional structure of these nanocrystals has been characterized with TEM
      tomography.

PMID- 16277447
TI  - Nanosphere induced gene expression in human dendritic cells.
AB  - The molecular mechanisms of nanosphere-induced mucosal immunization are important
      to decipher, since this can form the basis for novel approaches in, e.g., nasal
      vaccination. In this study, we have investigated the effect of nanospheres as
      antigen carriers on immature human dendritic cells. The results clearly indicate
      that tetanus toxoid immobilized nanospheres have a direct effect on human
      monocyte derived dendritic cells and induce a specific transcriptional profile
      involving genes crucial for phagocytosis and a protective immune response.

PMID- 16277448
TI  - Surface-driven bulk reorganization of gold nanorods.
AB  - Molecular dynamic simulations are used to study the structural stability of gold
      nanorods upon heating. We show that the global stability of the rod is governed
      by the free energetics of its surface. In particular, an instability of surface
      facets nucleates a bulk instability that leads to both surface and bulk
      reorganization of the rod. The surface reorganizes to form new, more stable,
      {111} facets, while the underlying fcc lattice completely reorients to align with
      this new surface structure. Rods with predominantly {111} facets remain stable
      until melting.

PMID- 16277449
TI  - Massive fabrication of free-standing one-dimensional Co/Pt nanostructures and
      modulation of ferromagnetism via a programmable barcode layer effect.
AB  - Massive fabrication of free-standing Co/Pt magnetic barcode nanowires with well
      defined interfaces and layer thicknesses is obtained after freeing them from
      porous templates. Such barcodes display bamboo-like shapes with identical motifs
      either inside or out of the templates. The ferromagnetism of these barcode
      nanowires can be modulated easily depending on the cobalt segments and shape
      anisotropies. Further enhancements of the ferromagnetism of Co/Pt barcodes are
      also accomplished through interfacial alloying processes via a thermally induced
      phase transition.

PMID- 16277450
TI  - Investigation of the connectivity of hydrophilic domains in Nafion using
      electrochemical pore-directed nanolithography.
AB  - A method of determining the connectivity of ion-conducting hydrophilic channels
      within the Nafion polymer electrolyte membrane by way of pore-directed
      nanolithography has been developed. Electrochemical etching of a silicon surface
      is performed through a Nafion-membrane mask. The resulting silicon surface imaged
      by tapping-mode atomic force microscopy (TMAFM) provides a footprint of the
      hydrophilic channels at the Nafion-silicon interface. In a similar fashion, a
      TMAFM phase-contrast image of the top surface of the Nafion mask prior to etching
      reveals the spatial distribution of hydrophilic domains at the surface of the
      polymer membrane. Collectively, these images provide detailed information about
      the structure of the hydrophilic channels at the top and bottom surfaces of the
      Nafion membrane. Autocorrelation statistical analysis of these two sets of images
      shows that only 48% of hydrophilic channels beginning at the Nafion surface
      connect to the silicon-Nafion interface.

PMID- 16277451
TI  - Achieving selective assembly with template topography and ultrasonically induced
      fluid forces.
AB  - A site-selective self-assembly technique called templated assembly by selective
      removal is introduced. Initial experiments demonstrated selective assembly of
      1.58 mum microspheres into shape-matched holes in a lithographically defined
      template. Very high frequency ultrasound selectively removes components from
      poorly matched holes. The successful demonstration of the technique was supported
      by detailed understanding and calculation of the kinematics of component removal
      in the ultrasonic field. The technique is expected to be scalable to smaller
      component sizes.

PMID- 16277452
TI  - Thermal conversion of bundled carbon nanotubes into graphitic ribbons.
AB  - High temperature heat treatment (HTT) of bundled single-walled carbon nanotubes
      (SWNTs) in vacuum ( approximately 10(-5) Torr) has been found to lead to the
      formation of two types of graphitic nanoribbons (GNRs), as observed by high
      resolution transmission electron microscopy. Purified SWNT bundles were first
      found to follow two evolutionary steps, as reported previously, that is, tube
      coalescence (HTT approximately 1400 degrees C) and then massive bond
      rearrangement (HTT approximately 1600 degrees C), leading to the formation of
      bundled multiwall nanotubes (MWNTs) with 3-12 shells. At HTT > 1800 degrees C, we
      find that these MWNTs collapse into multishell GNRs. The first type of GNR we
      observed is driven by the collapse of diameter-doubled single-wall nanotubes, and
      their production is terminated at HTT approximately 1600 degrees C when the MWNTs
      also start to form. We propose that the collapse is driven by van der Waals
      forces between adjacent tubes in the same bundle. For HTT > 2000 degrees C, the
      heat-treated material is found to be almost completely in the multishell GNR
      form.

PMID- 16277453
TI  - Surface dispersion and hardening of self-assembled diacetylene nanotubes.
AB  - We describe here the first method for dispersion of individual self-assembled
      diacetylene nanotubes on surfaces. Complete polymerization by UV exposure was
      achieved as demonstrated by nanotubes that were resistant to aggressive organic
      solvents and temperatures well above the melting point of the monomer. The
      polymerized tubes displayed reversible thermochromic and mechanochromic
      properties.

PMID- 16277454
TI  - Chiral symmetry breaking in two-dimensional C60-ACA intermixed systems.
AB  - We have demonstrated a method for fabricating C60 overlayers with controlled
      spacing and chirality by reactive coadsorption with the aromatic molecule
      acridine-9-carboxylic acid (ACA). Structural control is achieved by the
      mismatched symmetries of the coadsorbates, as well as specific intermolecular and
      adsorbate-substrate interactions. The resulting supramolecular structure has a
      C60 period nearly three times as large as the normal C60 2D packing of 1 nm and
      exists in enantiopure domains with robust chirality.

PMID- 16277455
TI  - Hot-drawing of single and multiwall carbon nanotube fibers for high toughness and
      alignment.
AB  - We report a new hot-drawing process for treating wet-spun composite fibers made
      of single- and multiwall carbon nanotubes and poly(vinyl alcohol). As shown in
      previous reports, untreated composite nanotube fibers exhibit a very large strain
      to-failure, and their toughness, which is the energy needed to break the fibers,
      exceeds that of any other known materials. However, untreated composite nanotube
      fibers absorb a very small amount of energy at low strain and become degraded in
      humid conditions. In this work, we use hot-drawing treatments, a concept inspired
      from textile technologies, to improve the properties of nanotube/PVA fibers. This
      treatment yields a crystallinity increase of the PVA and an unprecedented degree
      of alignment of the nanotubes. These structural modifications lead to a markedly
      improved energy absorption at low strain and make the fibers resistant to
      moisture. Hot-drawn nanotube/PVA fibers hold great potential for a number of
      applications such as bulletproof vests, protective textiles, helmets, and so
      forth.

PMID- 16277456
TI  - Electronic transport in carbon nanotubes with random coverage of physisorbed
      molecules.
AB  - The chemical sensitivity of electronic transport in carbon nanotubes under the
      physisorption of molecular species is investigated using a tight-binding scheme,
      parametrized by first-principles calculations. Such a computational method
      enables tackling of the complex electronic properties of chemically grafted
      conducting nanotubes. Our calculations demonstrate that the impact of
      physisorption on the transport regime critically depends on the HOMO-LUMO gap of
      the attached molecules. In addition, the electronic mean free path exhibits a
      downscaling law with a lower dependence on the coverage density of grafted
      molecules than for conventional substitutional doping or homogeneous disorder.

PMID- 16277457
TI  - Therapeutic nanoreactors: combining chemistry and biology in a novel triblock
      copolymer drug delivery system.
AB  - Triblock copolymeric nanoreactors are introduced as an alternative for liposomes
      as encapsulating carrier for prodrug activating enzymes. Inosine-adenosine
      guanosine preferring nucleoside hydrolase of Trypanosoma vivax, a potential
      prodrug activating enzyme, was encapsulated in nanometer-sized vesicles
      constructed of poly(2-methyloxazoline)-block-poly(dimethylsiloxane)-block-(2
      methyloxazoline) triblock copolymers. The nanoreactor is functionalized by
      incorporation of bacterial porins, OmpF or Tsx, in the reactor wall. Efficient
      cleavage of three natural substrates and one prodrug, 2-fluoroadenosine, by the
      nanoreactors was demonstrated.

PMID- 16277458
TI  - Thermal resistance of nanoscopic liquid-liquid interfaces: dependence on
      chemistry and molecular architecture.
AB  - Systems with nanoscopic features contain a high density of interfaces. Thermal
      transport in such systems can be governed by the resistance to heat transfer, the
      Kapitza resistance (RK), at the interface. Although soft interfaces, such as
      those between immiscible liquids or between a biomolecule and solvent, are
      ubiquitous, few studies of thermal transport at such interfaces have been
      reported. Here we characterize the interfacial conductance, 1/RK, of soft
      interfaces as a function of molecular architecture, chemistry, and the strength
      of cross-interfacial intermolecular interactions through detailed molecular
      dynamics simulations. The conductance of various interfaces studied here, for
      example, water-organic liquid, water-surfactant, surfactant-organic liquid, is
      relatively high (in the range of 65-370 MW/m2 K) compared to that for solid
      liquid interfaces ( approximately 10 MW/m2 K). Interestingly, the dependence of
      interfacial conductance on the chemistry and molecular architecture cannot be
      explained solely in terms of either bulk property mismatch or the strength of
      intermolecular attraction between the two phases. The observed trends can be
      attributed to a combination of strong cross-interface intermolecular interactions
      and good thermal coupling via soft vibration modes present at liquid-liquid
      interfaces.

PMID- 16277459
TI  - Mapping the fluorescence decay lifetime of a conjugated polymer in a phase
      separated blend using a scanning near-field optical microscope.
AB  - We have studied a blend of the polymers poly(9,9-dioctylfluorene) (F8) dispersed
      in an inert matrix of polystyrene (PS) using time-resolved scanning near-field
      optical microscopy (SNOM). On spin-casting, phase separation occurs between the
      two polymers resulting in a thin film characterized by an F8-rich phase and a PS
      rich phase. By spatially mapping the intensity of photoluminescence from the
      film, we find that there is a low concentration of F8 trapped within the PS-rich
      phase. We find that the fluorescence emission lifetime (measured at 440 nm) of F8
      trapped within the PS-rich phase is significantly longer than that from the F8
      rich phase (290 ps compared to 235 ps). Furthermore, spectral measurements
      indicate that the F8 emission from the PS-rich phase is characterized by a
      reduced fraction of emission from fluorenone defect states. Taken together, our
      measurements suggest that in the PS-rich phase interchain exciton diffusion
      between F8 molecules is suppressed significantly by the effect of dilution.

PMID- 16277460
TI  - Precise control of the Pt nanoparticle size by seeded growth using EO13PO30EO13
      triblock copolymers as protective agents.
AB  - Here, we report an efficient way to produce homogeneous Pt nanoparticles within a
      well-defined size range (3.5-6.6 nm) as a result of the seeded growth procedure
      using Pluronic L64 polymer capping agent. First, small seeds (3.5 nm) were
      prepared by the reduction of H2PtCl6.6H2O in water with NaBH4 in the presence of
      the capping poly(ethylene oxide)13-poly(propylene oxide)30-poly(ethylene oxide)13
      triblock copolymer at room temperature. Additional anionic Pt salt was then
      introduced under flowing H2 to obtain larger nanoparticles.

PMID- 16277461
TI  - Photoinduced interfacial charging and "explosion" of monolayer pentacene islands.
AB  - Electrostatic force microscopy shows that the electric field gradients above
      pentacene monolayer islands on 2-nm SiO2/Si substrates, in a dark, dry nitrogen
      environment, display a wide distribution of signs and magnitude that is dependent
      on sample history. Under 12 mW/cm2 green (532 nm) illumination, pentacene islands
      accumulate positive charge because of photoexcited electron transfer across the
      oxide to the Si substrate. At a strong illumination of 60 mW/cm2, pentacene
      islands reform into small spherical particles, apparently because the positive
      charge Coulomb repulsion energy becomes comparable to the cohesive energy of the
      pentacene monolayer.

PMID- 16277463
TI  - Nanopore tomography of a laser focus.
AB  - We demonstrate that the ionic current through a solid-state nanopore can be used
      to measure at single nanometer resolution the three-dimensional intensity profile
      of a laser directly in the focus of a microscope objective. We find a linear
      dependence of the ionic current on the incident laser power since the laser
      induced heat increases the temperature locally in the solution. Our data show a
      temperature increase of up to 20 K in the center of the focus for a laser
      wavelength of 1064 nm. Measurements of the two-dimensional temperature profiles
      at different positions along the optical axis allow us to reconstruct the three
      dimensional temperature profile of the laser focus, similar to tomography. Our
      new technique does not rely on the help of any optical elements and allows
      quantitative measurement of optical intensity or temperature distributions in
      aqueous environments with nanometer resolution.

PMID- 16277462
TI  - Calibration of dynamic molecular rulers based on plasmon coupling between gold
      nanoparticles.
AB  - Pairs of noble metal nanoparticles can be used to measure distances via the
      distance dependence of their plasmon coupling. These "plasmon rulers" offer
      exceptional photostability and brightness; however, the advantages and
      limitations of this approach remain to be explored. Here we report detailed
      plasmon peak versus separation calibration curves for 42- and 87-nm-diameter
      particle pairs, determine their measurement errors, and describe experimental
      procedures to improve their performance in biology, nanotechnology, and materials
      sciences.

PMID- 16277464
TI  - Electroluminescence from a single-nanocrystal transistor.
AB  - We report the fabrication and characterization of light-emitting transistors
      incorporating individual cadmium selenide (CdSe) nanocrystals. Electrical
      measurements conducted at low bias voltage and low temperature show clear
      evidence of Coulomb blockade behavior, indicating that electrons pass through the
      nanocrystal by single-electron tunneling. Once the bias voltage exceeds the band
      gap of CdSe, devices with asymmetric tunnel barriers emit linearly polarized
      light. Combined analyses of the electrical and optical data indicate that the
      tunnel couplings between the nanorod and the metallic electrodes change
      significantly as a function of bias voltage and light emission results from the
      inelastic scattering of tunneling electrons.

PMID- 16277465
TI  - Angle-resolved surface-enhanced Raman scattering on metallic nanostructured
      plasmonic crystals.
AB  - Surface-enhanced Raman scattering is an ideal tool for identifying molecules from
      the "fingerprint" of their molecular bonds; unfortunately, this process lacks a
      full microscopic understanding and, practically, is plagued with
      irreproducibility. Using nanostructured metal surfaces, we demonstrate strong
      correlations between plasmon resonances and Raman enhancements. Evidence for
      simultaneous ingoing and outgoing resonances in wavelength and angle sheds new
      light on the Raman enhancement process, allowing optimization of a new generation
      of reproducible Raman substrates.

PMID- 16277466
TI  - Structural transformations of carbon nanotubes under hydrostatic pressure.
AB  - We used simulations with a classical force field to study the transformation
      under hydrostatic pressure of isolated single-walled nanotubes (SWNT) from a
      circular to a collapsed cross section. Small-diameter SWNTs deform continuously
      under pressure, whereas larger-diameter SWNTs display hysteresis and undergo a
      first-order-like transformation. The different behavior is due to the changing
      proportions in the total energy of the wall-curvature energy and the van der
      Waals attraction between opposite walls of the tube.

PMID- 16277467
TI  - Nanofluidic diode and bipolar transistor.
AB  - Theoretical modeling of ionic distribution and transport in a nanochannel
      containing a surface charge on its wall, 30 nm high and 5 microm long, suggests
      that ionic current can be controlled by locally modifying the surface charge
      density through a gate electrode, even if the electrical double layers are not
      overlapped. When the surface charge densities at the right and left halves of a
      channel are the same absolute value but of different signs, this could form the
      basis of a nanofluidic diode. When the surface charge density at the middle part
      of a channel is modified, this could form the basis of a nanofluidic bipolar
      transistor.

PMID- 16277468
TI  - Low operating voltage single ZnO nanowire field-effect transistors enabled by
      self-assembled organic gate nanodielectrics.
AB  - The development of nanowire transistors enabled by appropriate dielectrics is of
      great interest for flexible electronic and display applications. In this study,
      nanowire field-effect transistors (NW-FETs) composed of individual ZnO nanowires
      are fabricated using a self-assembled superlattice (SAS) as the gate insulator.
      The 15-nm SAS film used in this study consists of four interlinked layer-by-layer
      self-assembled organic monolayers and exhibits excellent insulating properties
      with a large specific capacitance, 180 nF/cm2, and a low leakage current density,
      1 x 10(-8) A/cm2. SAS-based ZnO NW-FETs display excellent drain current
      saturation at Vds = 0.5 V, a threshold voltage (Vth) of -0.4 V, a channel
      mobility of approximately 196 cm2/V s, an on-off current ratio of approximately
      10(4), and a subthreshold slope of 400 mV/dec. For comparison, ZnO NW-FETs are
      also fabricated using 70-nm SiO2 as the gate insulator. Implementation of the SAS
      gate dielectric reduces the NW-FET operating voltage dramatically with more than
      1 order of magnitude enhancement of the on-current. These results strongly
      indicate that SAS-based ZnO NW-FETs are promising candidates for future flexible
      display and logic technologies.

PMID- 16277469
TI  - Core/multishell nanowire heterostructures as multicolor, high-efficiency light
      emitting diodes.
AB  - We report the growth and characterization of core/multishell nanowire radial
      heterostructures, and their implementation as efficient and synthetically tunable
      multicolor nanophotonic sources. Core/multishell nanowires were prepared by metal
      organic chemical vapor deposition with an n-GaN core and InxGa1-xN/GaN/p-AlGaN/p
      GaN shells, where variation of indium mole fraction is used to tune emission
      wavelength. Cross-sectional transmission electron microscopy studies reveal that
      the core/multishell nanowires are dislocation-free single crystals with a
      triangular morphology. Energy-dispersive X-ray spectroscopy clearly shows shells
      with distinct chemical compositions, and quantitatively confirms that the
      thickness and composition of individual shells can be well controlled during
      synthesis. Electrical measurements show that the p-AlGaN/p-GaN shell structure
      yields reproducible hole conduction, and electroluminescence measurements
      demonstrate that in forward bias the core/multishell nanowires function as light
      emitting diodes, with tunable emission from 365 to 600 nm and high quantum
      efficiencies. The ability to synthesize rationally III-nitride core/multishell
      nanowire heterostructures opens up significant potential for integrated nanoscale
      photonic systems, including multicolor lasers.

PMID- 16277471
TI  - Superhydrophobic films from raspberry-like particles.
AB  - We report a robust procedure for preparing superhydrophobic hybrid films on which
      the advancing contact angle for water is about 165 degrees and the roll-off angle
      of a 10-muL water droplet is 3 +/- 1 degrees . Dual-size surface roughness, which
      mimics the surface topology of self-cleaning plant leaves, originates from well
      defined silica-based raspberry-like particles that are covalently bonded to an
      epoxy-based polymer matrix. The roughened surface is chemically modified with a
      layer of poly(dimethylsiloxane) (PDMS). The robustness and simplicity of this
      procedure may make widespread applications of so-prepared superhydrophobic films
      possible.

PMID- 16277470
TI  - Cross-step place-exchange of oligo(phenylene-ethynylene) molecules.
AB  - We have observed nitro-functionalized oligo(phenylene-ethynylene) molecules
      exhibiting motion up and down Au{111} substrate monatomic step edges within host
      self-assembled monolayers of n-alkanethiols, independent of previously observed
      conductance switching. Single molecules have been imaged with scanning tunneling
      microscopy to place-exchange reversibly between the top and bottom of monatomic
      substrate step edges.

PMID- 16277472
TI  - Pristine semiconducting [110] silicon nanowires.
AB  - We report results of ab initio calculations on silicon nanowires oriented along
      the [110] direction and show for the first time that these pristine silicon
      nanowires are indirect band gap semiconductors. The nanowires have bulk Si core
      and are bounded by two (100) and two (110) planes in lateral directions. The
      (100) planes are atomically reconstructed with dimerization in a manner similar
      to the (100) surface of bulk Si but the dimer arrays are perpendicular to each
      other on the two (100) planes. An interesting consequence of surface
      reconstruction is the possibility of polytypism in thicker nanowires. We discuss
      its effects on the electronic structure. These findings could have important
      implications for the use of silicon nanowires in nanoscale devices as
      experimentally [110] nanowires have been found to grow preferentially in the
      small diameter range.

PMID- 16277473
TI  - Biomimetic synthesis of a H2 catalyst using a protein cage architecture.
AB  - A biomimetic approach has been used to develop an artificial hydrogenase that
      catalyses the efficient reduction of protons producing hydrogen gas. Analogous to
      the unique biological metal clusters found in hydrogenase enzymes, the engineered
      active sites are small, well-defined Pt clusters deposited on the interior of a
      heat shock protein cage architecture with stoichiometries of 150 to 1000 Pt per
      protein cage. The proton reduction reaction is driven by visible light through a
      coupled reaction with Ru(bpy)3(2+) and methyl viologen as an electron-transfer
      mediator. Hydrogen production rates are comparable to those of hydrogenase on a
      per protein basis and exceed production rates of other reported Pt-based
      catalysts. These results demonstrate the utility of a biomimetic approach toward
      addressing the needs of hydrogen production.

PMID- 16277474
TI  - Nanoscale optical imaging of excitons in single-walled carbon nanotubes.
AB  - We present simultaneous near-field photoluminescence (PL) and Raman imaging of
      single-walled carbon nanotubes (SWNTs) with a spatial resolution better than 15
      nm. Highly localized excitation is used to visualize the spatial extent of the
      contributing excited states. For SWNTs on glass, we typically observe highly
      confined PL from short segments of about 20 nm in length. The PL from micelle
      encapsulated SWNTs on mica is extended along the tube up to several hundreds of
      nanometers. We find that near-field enhancement is much stronger for
      photoluminescence than for Raman scattering, an observation that is explained by
      the low intrinsic quantum yield of SWNTs.

PMID- 16277475
TI  - Structural dependence of excitonic optical transitions and band-gap energies in
      carbon nanotubes.
AB  - The optical transitions of semiconducting carbon nanotubes have been ascribed to
      excitons. Here we use two-photon excitation spectroscopy to measure exciton
      binding energies, as well as band-gap energies, in a range of individual species
      of semiconducting SWNTs. Exciton binding energies are large and vary inversely
      with nanotube diameter, as predicted by theory. Band-gap energies are
      significantly blue-shifted from values predicted by tight-binding calculations.

PMID- 16277477
TI  - Nanolocalized nonlinear electron photoemission under coherent control.
AB  - We theoretically show that two-photon coherent control yields electron
      photoemission from metal nanostructures that is localized in nanosize hot spots
      whose positions are controllable on a nanometer scale, in agreement with recent
      experiments. We propose to use silver V-shapes as tailored nanoantennas for which
      the position of the coherently controllable photoelectron emission hot spot can
      be deterministically predicted. We predict that the low-frequency, high-intensity
      (quasi-stationary) excitation of the photoemission leads to an exponentially high
      contrast of the coherent control.

PMID- 16277476
TI  - Shape- and size-selective electrochemical synthesis of dispersed silver(I) oxide
      colloids.
AB  - Silver(I) oxide (Ag2O) micro- and nanoparticles were electrochemically
      synthesized by anodizing a sacrificial silver wire in a basic aqueous sulfate
      solution. Ag2O particles were released from the silver electrode surface during
      synthesis producing a visible sol "stream". The composition of these particles
      was established using selected area electron diffraction, X-ray diffraction, and
      X-ray photoelectron spectroscopy. The shape of Ag2O crystallites could be
      adjusted using the potential of the silver wire generator electrode. The
      generation of a dispersed Ag2O sol and the observed shape selectivity are both
      explained by a two-step mechanism involving the anodic dissolution of silver
      metal, Ag0 --> Ag+(aq) + 1e-, followed by the precipitation of Ag2O particles,
      2Ag+ + 2OH- --> Ag2O(s) + H2O. Within 100 mV of the voltage threshold for
      particle growth, cubic particles with a depression in each face ("hopper
      crystals") were produced. The application of more positive voltages resulted in
      the generation of 8-fold symmetric "flower"-shaped particles formed as a
      consequence of fast growth in the <111> crystallographic direction. The diameter
      of flower particles was adjustable from 250 nm to 1.8 microm using the growth
      duration at constant potential.

PMID- 16277478
TI  - Directional control in thermally driven single-molecule nanocars.
AB  - With the hope of directing future bottom-up fabrication through bulk external
      stimuli (such as electric fields) on nanometer-sized transporters, we sought to
      study controlled molecular motion on surfaces through the rational design of
      surface-capable molecular structures called nanocars. Here we show that the
      observed movement of the nanocars is a new type of fullerene-based wheel-like
      rolling motion, not stick-slip or sliding translation, due to evidence including
      directional preference in both direct and indirect manipulation and studies of
      related molecular structures.

PMID- 16277479
TI  - Plasmonic sensing characteristics of single nanometric holes.
AB  - The optical response of isolated holes in 20 nm thin gold is probed as a function
      of alkanethiol CH(3)(CH2)x SH (x epsilon in 1-15) and protein adsorption using
      dark-field spectroscopy. We establish that the plasmon excitations of single and
      short-range ordered 60 nm holes exhibit similar E-field decay lengths delta
      approximately 10-20 nm and that a single hole can be used to resolve the
      successive adsorption of a protein (biotin-BSA) and its interaction partner
      (neutravidin). The data confirm the localized character of the hole plasmon and
      demonstrate that its applicability for bio/chemosensing is similar to that of
      particle plasmons.

PMID- 16277480
TI  - Comment on "electronic transport, structure, and energetics of endohedral Gd@C82
      metallofullerenes".

PMID- 16277482
TI  - A general acid-base mechanism for the stabilization of a tetrahedral adduct in a
      serine-carboxyl peptidase: a computational study.
AB  - The QM/MM MD and free energy simulations show that serine-carboxyl peptidases
      (sedolisins) may stabilize the tetrahedral intermediates and tetrahedral adducts
      primarily through a general acid-base mechanism involving Asp (Asp164 for
      kumamolisin-As) rather than the oxyanion-hole interactions as in the cases of
      serine proteases.

PMID- 16277483
TI  - Locked nucleic acid molecular beacons.
AB  - A novel LNA-MB (molecular beacon based on locked nucleic acid bases) has been
      designed and investigated. It exhibits very high melting temperature and is
      thermally stable, shows superior single base mismatch discrimination capability,
      and is stable against digestion by nuclease and has no binding with single
      stranded DNA binding proteins. The LNA-MB will be widely useful in a variety of
      areas, especially for in vivo hybridization studies.

PMID- 16277484
TI  - Highly selective chromogenic and redox or fluorescent sensors of Hg2+ in aqueous
      environment based on 1,4-disubstituted azines.
AB  - Two new chemosensors that exhibit high affinity and high selectivity for Hg2+ in
      aqueous environment which operate through two different channels, optic/redox and
      optic/fluorescent, are reported. The optical change in sensing can be used even
      for a "naked-eye" detection of Hg2+ ions, whereas the fluorescent response can be
      modulated by varying the solvent polarity.

PMID- 16277485
TI  - Amine capture strategy for peptide bond formation by means of quinolinium
      thioester salts.
AB  - A new and unprecedented exploitation of quinolinium thioester salts 2 in peptide
      bond formation is reported. These synthetic tools were assessed during the
      preparation of a number of dipeptides 3a-f obtained in good yields with complete
      stereochemical integrity. A sequential mechanism related to a prior amine capture
      strategy is well-established. Additionally, a tripeptide 3g was prepared
      according to a "safety-catch" approach, thus demonstrating the important
      potential of these new synthetic tools in the design of new safety-catch linkers
      exploitable in Solid-Phase Peptide Synthesis (SPPS).

PMID- 16277486
TI  - Stable biomimetic super-hydrophobic engineering materials.
AB  - We describe a simple and inexpensive method to produce super-hydrophobic surfaces
      on aluminum and its alloy by oxidation and chemical modification. Water or
      aqueous solutions (pH = 1-14) have contact angles of 168 +/- 2 and 161 +/- 2
      degrees on the treated surfaces of Al and Al alloy, respectively. The super
      hydrophobic surfaces are produced by the cooperation of binary structures at
      micro- and nanometer scales, thus reducing the energies of the surfaces. Such
      super-hydrophobic properties will greatly extend the applications of aluminum and
      its alloy as lubricating materials.

PMID- 16277487
TI  - Iron-catalyzed olefin cis-dihydroxylation using a bio-inspired N,N,O-ligand.
AB  - Nature has evolved enzymes that carry out the cis-dihydroxylation of C=C bonds in
      the biodegradation of arenes in the environment. These enzymes, called Rieske
      dioxygenases, have mononuclear iron centers coordinated to a 2-His-1-carboxylate
      facial triad motif that has emerged as a common structural element among many
      nonheme iron enzymes. In contrast, olefin cis-dihydroxylation is conveniently
      carried out by OsO4 and related species in synthetic procedures. To develop more
      environmentally benign strategies for carrying out these transformations, we have
      designed Ph-DPAH [(di-(2-pyridyl)methyl)benzamide], a tridentate ligand that
      mimics the facial N,N,O site of the mononuclear iron center in the Rieske
      dioxygenases. Its iron(II) complex has been found to catalyze olefin cis
      dihydroxylation almost exclusively and with high H2O2 conversion efficiency on a
      wide range of substrates. and 18O labeling experiments suggest the participation
      of an FeV oxidant.

PMID- 16277488
TI  - Ionization spectroscopy of a DNA base: vacuum-ultraviolet mass-analyzed threshold
      ionization spectroscopy of jet-cooled thymine.
AB  - The high-resolution ionization spectroscopy of DNA bases is reported for the
      first time. Vacuum-UV mass-analyzed threshold ionization (VUV-MATI) spectrum of
      jet-cooled thymine provides not only the most precise ionization potential but
      also its vibrational structure in the ground cationic state.

PMID- 16277489
TI  - Anodic preparation of [Re2Cp2(CO)6]2+: a dimeric dication that provides the
      powerful one-electron oxidant [ReCp(CO)3]+.
AB  - The half-sandwich piano-stool compounds Re(eta5-C5R5)(CO)3 (1, R = H; or 2, R =
      Me) are oxidized to the corresponding 17-electron Re(II) cations at glassy carbon
      anodes in CH2Cl2/[NBu4][B(C6F5)4]. Despite the very strongly positive E1/2 values
      of the couples (1.16 V for 1/1+ and 0.91 V for 2/2+ vs ferrocene/ferrocenium),
      the radical cations are persistent in this medium and exist in equilibrium with
      the corresponding dimeric dications, which may be cathodically reduced back to
      the neutral starting material. DFT calculations show that the dimer of 1+
      achieves its stability through formation of a single long (almost 3.3 A) Re-Re
      bond made possible when the HOMO in 1 is rehybridized away from the metal in the
      one-electron oxidation process. The pure salts [1][B(C6F5)4]2 and [2][B(C6F5)4]2
      were isolated by preparative anodic electrochemistry. The former may be used for
      storage of the very strong one-electron oxidant 1+, which was used to prepare a
      number of oxidation products as their [B(C6F5)4]- salts.

PMID- 16277490
TI  - How bulky is a bulky ligand: energetic consequences of steric constraint in
      ligand-directed cluster assembly and disassembly.
AB  - Steric tuning of N-aryl groups of homologous amidinate ligands affords discrete
      dimeric and tetrameric copper(I) clusters in solid state, but they undergo
      dynamic dimer-dimer and tetramer-dimer interconversion in solution. A delicate
      interplay between steric constraint and mechanical stability shapes the reaction
      coordinate of this process. Thermodynamic and kinetic parameters dictating such
      cluster assembly and disassembly immediately suggest a means to experimentally
      quantify energies that are associated with ligand steric bulk.

PMID- 16277491
TI  - Gold-caged metal clusters with large HOMO-LUMO gap and high electron affinity.
AB  - We report a series of isoelectronic gold-caged metal clusters, M@Au14 (M = Zr,
      Hf), and anion clusters, M@Au14- (M = Sc, Y), all having a calculated HOMO-LUMO
      gap larger than the well-known tetrahedral cluster Au20-the 3D metal cluster with
      a very large measured HOMO-LUMO gap (1.77 eV). The clusters M@Au14 (M = Sc, Y)
      also exhibit a calculated electron affinity (EA) and vertical detachment energy
      (VDE) not only higher than the "superhalogen" icosahedral Al13 cluster but also
      possibly even higher than a Cl atom which has the highest (measured) elemental EA
      or VDE (3.61 eV).

PMID- 16277492
TI  - Electron-precise/deficient La(5-x)Ca(x)Ge4 (3.4 < or = x < or = 3.8) and Ce(5
      x)Ca(x)Ge4 (3.0 < or = x < or = 3.3): probing low-valence electron concentrations
      in metal-rich Gd5Si4-type germanides.
AB  - We report for the first time the syntheses of electron-precise/deficient alloys,
      Ln5-xCaxGe4 (Ln = La, Ce; x = 3.37, 3.66, 3.82 for La; x = 3.00, 3.20, 3.26 for
      Ce), in the metal-rich R5Tt4 Zintl system (R = rare earth metal; Tt = Si, Ge).
      The new alloys extend the phase width from electron-rich to open-shell electron
      deficient region in the metal-rich Zintl system and demonstrate possible
      occurrence of varied electron deficiencies in Zintl phases without structural
      changes, as a result of other existing structure-forming factors.

PMID- 16277493
TI  - Carbon-to-metal hydrogen atom transfer: direct observation using time-resolved
      infrared spectroscopy.
AB  - We report the direct spectroscopic observation of hydrogen atom transfer
      reactions from carbon to metals, in which homolytic cleavage of a C-H bond is
      accomplished at a single metal center. Laser flash photolysis (355 nm) of a
      solution of [Cp(CO)2Os]2 leads to homolysis of the Os-Os bond and formation of
      the osmium-centered radical, Cp(CO)2Os*, as observed by time-resolved infrared
      (TRIR) spectroscopy. DFT computations on Cp(CO)2Os* support this assignment.
      Continuous photolysis (lambda > 300 nm) of [Cp(CO)2Os]2 in the presence of excess
      1,4-cyclohexadiene produces the osmium hydride Cp(CO)2OsH. The kinetics of this
      carbon-to-metal hydrogen atom transfer were examined by TRIR spectroscopy. The
      second-order rate constant for hydrogen atom transfer from 1,4-cyclohexadiene to
      Cp(CO)2Os* in hexane at 23 degrees C is kH = (2.1 +/- 0.2) x 106 M-1 s-1. The pKa
      of Cp(CO)2OsH was determined as 32.7 in CH3CN, and use of a thermochemical cycle
      provided an estimated lower limit of 82 kcal/mol for the Os-H bond dissociation
      energy, indicating that it is an exceptionally strong M-H bond. Photolysis of
      [Tp(CO)2Os]2 (Tp = hydridotris(pyrazolyl)borate) results in carbon-to-metal
      hydrogen atom transfers from even stronger C-H bonds (THF or toluene) and
      produces Tp(CO)2OsH.

PMID- 16277494
TI  - Millimeter scale alignment of magnetic nanoparticle functionalized microtubules
      in magnetic fields.
AB  - The conjugation of 14 nm diameter CoFe2O4 nanoparticles to the surface of
      biotinylated microtubules enables their manipulation with externally applied
      magnetic fields of small, permanent NdFeB magnets. Microtubules are selectively
      patterned on kinesin motor-modified glass surfaces in coparallel arrays that
      mimic the orientation of the magnetic field lines over millimeter distances. The
      magnetic field is simultaneously used to increase surface loading of
      microtubules. We demonstrate that motility across the kinesin motor surface is
      retained following magnetic functionalization of the microtubules, while gliding
      speed is dependent on loading level of the neutravidin linker as well as magnetic
      nanoparticles.

PMID- 16277495
TI  - AFM single molecule experiments at the solid-liquid interface: in situ
      conformation of adsorbed flexible polyelectrolyte chains.
AB  - This paper reports the in situ study of conformations of flexible synthetic
      polymer molecules of protonated poly(2-vinylpyridine) at the solid-liquid
      interface at different pH of aqueous solutions. The direct conformation study of
      such thin ( approximately 0.4 nm) single molecules under liquid is performed for
      the first time. The highly protonated poly(2-vinylpyridine) chains possess a
      conformation of 2D equilibrated random coil, while at low degree of protonation,
      molecules are in the conformation of a strongly compressed 3D coil. Molecules are
      immobile during the few hours of the AFM experiment.

PMID- 16277497
TI  - Color-tunable photoluminescence of alloyed CdS(x)Se(1-x) nanobelts.
AB  - High-quality CdSxSe1-x nanobelts of variable composition (0 </= x </= 1) were
      fabricated by a simple one-step thermal evaporation route. Photoluminescence
      measurements showed that all the CdSxSe1-x nanobelts have a single near-bandedge
      emission band, and their spectral maximum positions can be tuned from
      approximately 508 nm (for pure CdS) to approximately 705 nm (for pure CdSe).
      These kinds of nanobelts may have potential applications in adjustable nano/micro
      photoelectric devices in the visible region.

PMID- 16277496
TI  - The burial of solvent-accessible surface area is a predictor of polypeptide
      folding and misfolding as a function of chain elongation.
AB  - The hydrophobic effect is a major driving force in all chemical and biological
      events involving chain collapse in aqueous solution. Here, we show that the
      burial of nonpolar solvent-accessible surface area (NSASA) is a powerful
      criterion to predict the folding and misfolding behavior of small single-domain
      proteins as a function of chain elongation. This bears fundamental implications
      for co- and post-translational protein folding in the cell and for understanding
      the interplay between noncovalent interactions and formation of native-like
      structure and topology. Comparison between the fraction of NSASA in fully
      unfolded and folded elongating chains shows that efficient burial of nonpolar
      surface area is preferentially achieved only when the polypeptide chain is almost
      complete. This effect has no preferential vectorial character in that it is
      present upon elongation from both the N and C termini. For incomplete chains that
      do not have the ability to fold and bury nonpolar surface intramolecularly, the
      overall hydrophobic nature of the polypeptide chain (expressed as FBA, i.e.,
      fractional buried surface area per residue) dictates the tendency toward
      misfolding and self-association. N-terminal chains characterized by FBA exceeding
      0.73 are likely to misfold and aggregate, if unable to fold intramolecularly.

PMID- 16277498
TI  - Self-assembly of hollow cones in a bola-amphiphile/hexadiamine salt solution.
AB  - Cones are a very rare form of supramolecular self-assembly. It is shown that
      mixing of an unsymmetrical bola-fatty acid and a diamine (catanionic system) in
      dilute solutions can produce aggregates having a conical shape. These assemblies
      are made of frozen unsymmetrical monolayers in which bolas are arranged on a
      regular hexagonal lattice. Cones are stabilized by the introduction of pentagonal
      or n-gonal defects in the bola-lattice which yields the quantification of the
      cone apex angle according to the Euler theorems. The formation of cones
      represents a novel route for lipid and surfactant systems to minimize the edge
      energy of a flat membrane.

PMID- 16277499
TI  - Bronsted acid-catalyzed imine amidation.
AB  - A new method for the Bronsted acid-catalyzed addition of amide nucleophiles to
      imines to produce protected aminal products is described. Simple Bronsted acids
      (phenyl phosphinic acid and trifluoromethanesulfonimide) were shown to be
      excellent catalysts, providing high yields of the aminal product. A catalytic
      asymmetric imine amidation using sulfonamides as nucleophiles was successful when
      a hindered biaryl phosphoric acid catalyst derived from 2,2'-diphenyl-[3,3'
      biphenanthrene]-4,4'-diol (VAPOL) was used. Excellent yields and
      enantioselectivities were found in these additions (up to 99% ee).

PMID- 16277500
TI  - Self-catalytic behavior of carbon nanotubes.
AB  - Self-catalytic behavior of multi-walled carbon nanotubes is proposed and
      validated experimentally under the conditions in which metal catalysis was
      previously figured to work only. The self-catalysis could support the nanotube
      nucleation and radial and axial developing processes. This result should lead to
      a new and better understanding of the growth mechanism of carbon nanotubes in a
      metal catalytic process.

PMID- 16277501
TI  - High performance organic field-effect transistors based on amphiphilic
      tris(phthalocyaninato) rare earth triple-decker complexes.
AB  - LB films of three amphiphilic tris(phthalocyaninato) rare earth triple-decker
      complexes with crown-ethers as hydrophilic heads and long alkyl chains as
      hydrophobic tails have been prepared and found to display very well ordered layer
      structures, as proved by pi-A isotherms, UV-vis and polarized absorption spectra,
      X-ray diffraction experiments, and microscopic morphology characterization. These
      LB films have been fabricated into field-effect transistor (FET) devices, which
      show carrier mobilities as high as 0.24-0.60 cm2 V-1 s-1, among the highest
      mobilities achieved thus far for all LB film-based OFETs.

PMID- 16277502
TI  - Carbon monoxide-promoted carbene insertion into the aryl substituent of an N
      heterocyclic carbene ligand: Buchner reaction in a ruthenium carbene complex.
AB  - In the presence of carbon monoxide, ruthenium carbenes give a net insertion/ring
      expansion (Buchner reaction) into one of the aromatic rings of the N-heterocyclic
      carbene ligand. In alkene metathesis applications, the N-heterocyclic carbene
      ligand is both robust and typically inert to reactions with the metal-bound
      carbene. This unique reaction is completely regioselective. The complexes
      obtained through ring expansion were fully characterized in the solid state using
      X-ray crystallography and in solution using NMR and IR spectroscopy.

PMID- 16277503
TI  - Total synthesis of piericidin A1 and B1.
AB  - The first total syntheses of piericidin A1 and B1 are disclosed and unambiguously
      establish the relative and absolute stereochemistry of the natural products by an
      approach that will facilitate the synthesis of a series of analogues. Central to
      the approach is an inverse electron demand Diels-Alder reaction of a N-sulfonyl-1
      aza-1,3-butadiene with tetramethoxyethene followed by Lewis acid-promoted
      aromatization used to assemble the functionalized pyridine core. Additional key
      elements in the convergent approach include the use of an anti-aldol reaction to
      install the C9 and C10 relative and absolute stereochemistry, a modified Julia
      olefination for formation of the C5-C6 trans double bond with convergent
      assemblage of the side chain, and a penultimate heterobenzylic Stille cross
      coupling reaction of the pyridyl core with the fully elaborated side chain.

PMID- 16277504
TI  - Nickel-catalyzed trans-alkynylboration of alkynes via activation of a boron
      chlorine bond.
AB  - Reaction of (diisopropylamino)chloroboryl ethers of alkynols with
      alkynylstannanes in the presence of nickel catalysts afforded formal trans
      alkynylboration products in good yields. The products were isolated as pinacol
      boronates after treatment of the crude reaction mixture with acetic anhydride and
      pinacol in the presence of a base. The trans-alkynylboration products underwent
      Suzuki-Miyaura coupling reaction with organic halides. A 2-borylalkenylnickel(II)
      complex, in which the boryl and nickel groups are located in a trans fashion, was
      isolated in a reaction of the chloroboryl ether with a single equivalent of a
      nickel(0)-phosphine complex.

PMID- 16277506
TI  - Asymmetric multicomponent domino reactions and highly enantioselective conjugated
      addition of thiols to alpha,beta-unsaturated aldehydes.
AB  - An organocatalytic asymmetric multicomponent domino and a conjugated addition
      reaction to alpha,beta-unsaturated aldehydes are presented. The development is
      based, first, on an organocatalyzed highly enantioselective nucleophilic thiol
      addition to the beta-carbon atom in the iminium ion intermediate, followed by an
      electrophilic amination of the alpha-carbon atom to the enamine intermediate. The
      multicomponent reactions proceed to give enantiopure amino-thiols in moderate to
      good yields. Furthermore, the organocatalyzed thiol addition to alpha,beta
      unsaturated aldehydes takes place in good yields and excellent
      enantioselectivities.

PMID- 16277505
TI  - Activation of orotidine 5'-monophosphate decarboxylase by phosphite dianion: the
      whole substrate is the sum of two parts.
AB  - We report that the binding of phosphite dianion to orotidine 5'-monophosphate
      decarboxylase (OMPDC) results in an 80 000-fold increase in kcat/Km for
      decarboxylation of the truncated substrate, 1-(beta-d-erythrofuranosyl)orotic
      acid (EO), which lacks a 5'-phosphodianion moiety. The intrinsic binding energy
      (IBE) of phosphite dianion in the transition state is 7.8 kcal/mol, which
      represents a very large fraction of the 11.8 kcal/mol IBE of the phosphodianion
      group of the natural substrate orotidine 5'-monophosphate (OMP). The data give
      kcat = 160 +/- 70 s-1 for turnover of EO in the active site of OMPDC containing
      phosphite dianion, which is significantly larger than kcat = 15 s-1 for turnover
      of OMP. Despite the weaker binding of the individual EO and HPO32- "parts" (KmKd
      = 0.014 M2) than of OMP (Km = 1.6 x 10-6 M), once bound, OMPDC provides a
      slightly greater stabilization of the transition state for reaction of the parts
      than of the whole substrate. Thus, the covalent connection between the reacting
      portion of the substrate and the nonreacting phosphodianion group is not
      necessary for efficient catalysis. This implies that a major role of the
      phosphodianion group of OMP is to provide binding interactions that are used to
      drive an enzyme conformational change, resulting in formation of an active site
      environment optimized for transition state stabilization.

PMID- 16277507
TI  - An expeditious total synthesis of (+/-)-stenine.
AB  - (+/-)-Stenine was synthesized in eight steps from a known ketophosphonate
      reagent. The key step was an exo-selective Diels-Alder/intramolecular Schmidt
      domino reaction that afforded three of the four rings and four stereocenters in a
      single reaction.

PMID- 16277508
TI  - Stable triplet of uracil-uracil basepairs in a small antisense RNA.
AB  - The interaction between ant (antirepressor) mRNA and its antisense RNA, sar
      (small antisense RNA), is important in regulation of the development of
      bacteriophage P22. Sar is 68-69 nucleotides in length and is believed to consist
      of two hairpin structures separated by a small inter-hairpin region, followed by
      a short 3' tail [Schaefer and McClure RNA 1997, 3, 141-156]. A novel feature of
      the proposed secondary structure of the first hairpin is a extremely rare triple
      U:U base stack. Heteronuclear NMR studies presented here show that the first
      hairpin does not possess a unique structure in the absence of the second hairpin.
      However, it acquires a well-defined structure within full length sar. Remarkably,
      the triple U:U stack appears to be a stable feature of the first hairpin,
      regardless of the presence or absence of the second hairpin.

PMID- 16277509
TI  - Synthesis of fused polycyclic aromatics by palladium-catalyzed annulation of
      arynes using 2-halobiaryls.
AB  - The Pd-catalyzed annulation of arynes by 2-halobiaryls and related vinylic
      halides provides a very efficient, high yielding synthesis of polycyclic aromatic
      and heteroaromatic hydrocarbons. This process appears to involve the catalytic,
      stepwise coupling of two very reactive substrates, an aryne and an
      organopalladium species, to generate excellent yields of cross-coupled products.

PMID- 16277510
TI  - High yield solution-liquid-solid synthesis of germanium nanowires.
AB  - High yields of crystalline Ge nanowires were synthesized for the first time in a
      conventional solvent of trioctylphosphine by disproportionating GeI2 in the
      presence of Bi nanoparticle growth seeds at 350 degrees C and atmospheric
      pressure.

PMID- 16277511
TI  - Determination of a large reorganization energy barrier for hydride abstraction by
      glucose oxidase.
AB  - Glucose oxidase mediates the aerobic oxidation of simple sugars to lactones using
      a noncovalently bound flavin cofactor. The chemical mechanism of this reaction
      has been uncertain for many years. Here it is shown, using enzymes reconstituted
      with chemically modified cofactors, that sugar oxidation most likely occurs by
      concerted hydride (H-) abstraction. Studies of the kinetics and thermodynamics
      together with the application of Marcus theory reveal a large reorganization
      energy barrier. The magnitude of this intrinsic contribution appears
      characteristic of H- transfer in proteins and in solution. The observation that
      neither the thermodynamics nor reorganization energy is significantly altered in
      the glucose oxidase active site raises questions concerning how the redox
      reaction may be catalyzed.

PMID- 16277512
TI  - Route to GaN and VN assisted by carbothermal reduction process.
AB  - A route to prepare nitrides, such as GaN, VN, and other nitrides, is reported.
      The reaction pathway involves a two-step process by using the as-synthesized a
      C3N3.69 as precursor. The route is so potent that a series of nitrides can be
      directly synthesized from their oxides at moderate temperatures. A striking
      feature of this method lies in that a-C3N3.69 is found to play double roles as
      both carbonizing and nitridizing agent in these reactions. These results will
      greatly deepen our understandings of the mechanism for solid-state metathesis
      reactions.

PMID- 16277513
TI  - Chirality- and diameter-dependent reactivity of NO2 on carbon nanotube walls.
AB  - We report the density-functional calculations of NO2 adsorption on single-walled
      carbon nanotube walls. A single molecular adsorption was endothermic with an
      activation barrier, but a collective adsorption with several molecules became
      exothermic without an activation barrier. We find that NO2 adsorption is strongly
      electronic structure- and strain-dependent. The NO2 adsorption on metallic
      nanotubes was energetically more favorable than that on semiconducting nanotubes
      and furthermore the adsorption became less stable with increasing diameters of
      nanotubes. The adsorption barrier height shows similar dependence on the
      electronic structure and diameter to the adsorption energy. Our theoretical model
      can be a good guideline for the separation of nanotubes by electronic structures
      using various adsorbates.

PMID- 16277514
TI  - One-electron reduction potential for oxygen- and sulfur-centered organic radicals
      in protic and aprotic solvents.
AB  - We estimated one-electron reduction potentials of redox-active organic molecules
      for a spectrum of eight different functional groups (phenoxyl, p-benzoquinone,
      phenylthiyl, p-benzodithiyl, carboxyl, benzoyloxyl, carbthiyl, and benzoylthiyl)
      in protic (water) and aprotic (acetonitrile, N,N-dimethylacetamide) solvents.
      Electron affinities (EA) were evaluated in a vacuum with high level quantum
      chemical methods using Gaussian3-MP2 (G3MP2) and Becke 3 Lee, Yang, and Parr
      functional B3LYP with aug-cc-pVTZ basis set. To evaluate one-electron redox
      potentials, gas-phase free energies were combined with solvation energies
      obtained in a two-step computational approach. First, atomic partial charges were
      determined in a vacuum by the quantum chemical method B3LYP/6-31G(d,p). Second,
      solvation energies were determined, solving the Poisson equation with these
      atomic partial charges. Redox potentials computed this way, compared to
      experimental data for the 21 considered organic compounds in different solvents,
      yielded overall root-mean-square deviations of 0.058 and 0.131 V using G3MP2 or
      B3LYP to compute electronic energies, respectively, while B3LYP/6-31G(d,p) was
      used to compute solvation energies.

PMID- 16277515
TI  - 1,8-Bis(hexamethyltriaminophosphazenyl)naphthalene, HMPN: a superbasic
      bisphosphazene "proton sponge".
AB  - It is shown that a combination of Schwesinger's phosphazene base concept and the
      idea of the disubstituted 1,8-naphthalene spacer, first introduced by Alder in
      paradigmatic 1,8-bis(dimethylamino)naphthalene (DMAN), yields a new superbase,
      HMPN, which represents the up to date most basic representative of this class of
      "proton sponges", as evidenced by the theoretically estimated proton affinity PA
      = 274 kcal/mol and the measured pK(BH+) (MeCN) 29.9 +/- 0.2. HMPN is by nearly 12
      orders of magnitude more basic than Alder's classical 1,8
      bis(dimethylamino)naphthalene (DMAN). The title compound, HMPN, is prepared and
      fully characterized. The spatial structure of HMPN and its conjugate acid is
      determined by X-ray technique and theoretical DFT calculations. It is found that
      monoprotonated HMPN has an unsymmetrical intramolecular hydrogen bridge (IHB).
      This cooperative proton chelating effect renders the bisphosphazene more basic
      than Schwesinger's set of "monodentate" P1 phosphazene bases. The density
      functional calculations are in good accordance with the experimental results,
      providing some complementary information. They conclusively show that the high
      basicity of HMPN is a consequence of the high energy content of the base in its
      initial neutral state and the intramolecular hydrogen bonding in the resulting
      conjugate acid with contributions to proton affinity of 14.1 and 9.5 kcal/mol,
      respectively.

PMID- 16277516
TI  - Slow diffusion by singlet state NMR spectroscopy.
AB  - Small diffusion coefficients can be measured by using populations of singlet
      states that have a relaxation time constant, T(s), which can be much longer than
      the longitudinal relaxation time, T1. Spatial information can be encoded with
      pulsed field gradients in the manner of stimulated echo sequences. Singlet states
      can be excited via double-quantum coherences to enhance the efficiency of phase
      encoding and decoding.

PMID- 16277517
TI  - Enzymatic synthesis of layered titanium phosphates at low temperature and neutral
      pH by cell-surface display of silicatein-alpha.
AB  - We introduce a novel method of inorganic synthesis using the catalytic and
      structure-directing properties of the demosponge enzyme silicatein-alpha.
      Recombinant silicatein-alpha was displayed at the surface of Escherichia coli
      cells by fusion to outer membrane protein A and used to biocatalytically direct
      the formation of layered and amorphous titanium phosphates from a small water
      soluble precursor at near-neutral pH at 16 degrees C. Synthesis of titanium
      phosphates, with potential applications in catalysis and separation technology,
      previously has required prolonged reactions with phosphoric acid at elevated
      temperatures. Additionally, we use library screening to isolate a 15-mer with
      affinity toward the silicatein active site (Kd ca. 50 nM) and introduce this new
      approach to demonstrate the success of our display strategy. Considering our
      previous findings with native silicatein filaments, we suggest that this
      scalable, efficient, cell-based system may have a broad utility for the synthesis
      of a range of structured metallophosphates and other inorganic materials.

PMID- 16277518
TI  - Nonradical zinc-Barbier reaction for diastereoselective synthesis of vicinal
      amino alcohols.
AB  - A new protocol for the synthesis of vicinal amino alcohols is described. The
      method employs a Barbier-type reaction between an imine and 3-benzoyloxyallyl
      bromide in the presence of zinc metal. The addition products are debenzoylated to
      afford amino alcohols in good yields and with diastereomeric ratios greater than
      85:15 in favor of the anti isomer. A Hammett study has been performed which
      strongly indicates that the allylation does not follow a radical mechanism, but
      instead an organometallic reagent is formed which subsequently reacts with the
      imine. A computational study based on this mechanism reproduces the observed
      diastereoselectivity with high accuracy, but only when a sufficiently large
      portion of the substrate is included.

PMID- 16277519
TI  - Octasubstituted metal-free phthalocyanine as core of phosphorus dendrimers: a
      probe for the properties of the internal structure.
AB  - The synthesis of a new family of phosphorus dendrimers built from an
      octasubstituted metal-free phthalocyanine core is described up to generation 5.
      This core is used as a sensor and a probe for analyzing the properties of the
      internal structure and the influence of each structural part (core, branches,
      surface) upon the whole structure. UV-visible spectra show both a hyperchromic
      and bathochromic effect on the Q-bands with increasing generation, indicating
      that the chromophore is more isolated, and that the dendritic shell mimics a
      highly polar solvent. There is no evidence for aggregation, except for generation
      0, showing again the isolation of the core. However, the dendritic shell is
      permeable to aqueous acids and bases, as demonstrated by the reversible splitting
      of the Q-band in an acidic medium (neutral form of the phthalocyanine) and the
      single Q-band in a basic medium (dianionic form), even for generation 4. The
      fluorescence quantum yield for the neutral form increases with increasing
      generation. The dianionic form of generation 0 is poorly fluorescent, whereas
      generations 3 and 4 (G3 and G4) exhibit better fluorescence. The cores of G3 and
      G4 are highly sensitive optical sensors for H3O+ and OH-. These experiments are
      carried out in THF/water mixtures, and the influence of water on the structure
      has been checked. The hydrodynamic radius of generation 4 is measured by NMR
      diffusion (pulse gradient spin-echo) experiments. R(H) varies from 35.4 A at 4
      mol % of water to 32.5 A at 64 mol % of water in THF, indicating the hydrophobic
      nature of these dendrimers.

PMID- 16277520
TI  - Nonlinear optical studies of the agricultural antibiotic morantel interacting
      with silica/water interfaces.
AB  - It is now known that the untreated discharge of pharmaceuticals into the
      environment can impact human health and development and lead to increased drug
      resistance in biota. Here, we present the first direct interface-specific studies
      that address the mobility of the widely used agricultural antibiotic morantel,
      which is commonly present in farm runoff. Surface-bound morantel was
      spectroscopically identified using second harmonic generation (SHG) via a two
      photon resonance of its n-pi* transition and in the C-H stretching region by
      vibrational sum frequency generation (VSFG). Resonantly enhanced SHG adsorption
      isotherm measurements carried out at the silica/water interface between 6 x 10(
      7) and 5 x 10(-5) M morantel concentration result in a free energy of adsorption
      of 42(2) kJ/mol at pH 7. Finally, real-time tracking of morantel interaction with
      the silica/water interface shows that the binding events are fully reversible,
      consistent with its high mobility in silica-rich soil environments. This work
      thus indicates that pharmaceuticals discharged into the environment can enter the
      groundwater supply of municipal water systems, at which point their removal is
      challenging. In addition, the high mobility of morantel in silica-rich soil
      environments could lead to developing increased interaction of this antibiotic
      with target organisms, which could respond by increased drug resistance.

PMID- 16277521
TI  - Active site structure of class I ribonucleotide reductase intermediate X: a
      density functional theory analysis of structure, energetics, and spectroscopy.
AB  - Several models for the active site structure of class I ribonucleotide reductase
      (RNR) intermediate X have been studied in the work described in this paper, using
      broken-symmetry density functional theory (DFT) incorporated with the conductor
      like screening (COSMO) solvation model. The calculated properties, including
      geometries, spin states, 57Fe, 1H, and 17O hyperfine tensors, Mossbauer isomer
      shifts, and quadrupole splittings, and the estimation of the Fe(IV) d-d
      transition energies have been compared with the available experimental values. On
      the basis of the detailed analysis and comparisons, we propose a definite form
      for the active site structure of class I RNR intermediate X, which contains an
      Fe1(III)Fe2(IV) center (where Fe1 is the iron site closer to Tyr122, and the two
      iron sites are high-spin antiferromagnetically coupled to give a total 1/2 net
      spin), two mu-oxo bridges, one terminal water which binds to Fe1(III) and also H
      bonds to both side chains of Asp84 and Glu238, and one bidentate carboxylate
      group from the side chain of Glu115.

PMID- 16277522
TI  - Microwave-enhanced reaction rates for nanoparticle synthesis.
AB  - Microwave reactor methodologies are unique in their ability to be scaled-up
      without suffering thermal gradient effects, providing a potentially industrially
      important improvement in nanocrystal synthetic methodology over convective
      methods. Synthesis of high-quality, near monodispersity nanoscale InGaP, InP, and
      CdSe have been prepared via direct microwave heating of the molecular precursors
      rather than convective heating of the solvent. Microwave dielectric heating not
      only enhances the rate of formation, it also enhances the material quality and
      size distributions. The reaction rates are influenced by the microwave field and
      by additives. The final quality of the microwave-generated materials depends on
      the reactant choice, the applied power, the reaction time, and temperature. CdSe
      nanocrystals prepared in the presence of a strong microwave absorber exhibit
      sharp excitonic features and a QY of 68% for microwave-grown materials. InGaP and
      InP are rapidly formed at 280 degrees C in minutes, yielding clean reactions and
      monodisperse size distributions that require no size-selective precipitation and
      result in the highest out of batch quantum efficiency reported to date of 15%
      prior to chemical etching. The use of microwave (MW) methodology is readily
      scalable to larger reaction volumes, allows faster reaction times, removes the
      need for high-temperature injection, and suggests a specific microwave effect may
      be present in these reactions.

PMID- 16277523
TI  - Practical route to relative diffusion coefficients and electronic relaxation
      rates of paramagnetic metal complexes in solution by model-independent outer
      sphere NMRD. Potentiality for MRI contrast agents.
AB  - The relaxation of electronic spins S of paramagnetic species is studied by the
      field-dependence of the longitudinal, transverse, and longitudinal in the
      rotating frame relaxation rates R1, R2, and R1rho of nuclear spins I carried by
      dissolved probe solutes. The method rests on the model-independent low-frequency
      dispersions of the outer-sphere (OS) paramagnetic relaxation enhancement (PRE) of
      these rates due to the three-dimensional relative diffusion of the complex with
      respect to the probe solute. We propose simple analytical formulas to calculate
      these enhancements in terms of the relative diffusion coefficient D, the
      longitudinal electronic relaxation time T1e, and the time integral of the time
      correlation function of the I-S dipolar magnetic interaction. In the domain of
      vanishing magnetic field, these parameters can be derived from the low-frequency
      dispersion of R1 thanks to sensitivity improvements of fast field-cycling nuclear
      relaxometers. At medium field, we present various approaches to obtain these
      parameters by combining the rates R1, R2, and R1rho. The method is illustrated by
      a careful study of the proton PREs of deuterated water HOD, methanol CH3OD, and
      tert-butyl alcohol (CH3)3COD in heavy water in the presence of a recently
      reported nonacoordinate Gd(III) complex. The exceptionally slow electronic
      relaxation of the Gd(III) spin in this complex is confirmed and used to test the
      accuracy of the method through the self-consistency of the low- and medium-field
      results. The study of molecular diffusion at a few nanometer scale and of the
      electronic spin relaxation of other complexed metal ions is discussed.

PMID- 16277524
TI  - Thioredoxin and lipoic acid catalyze the denitrosation of low molecular weight
      and protein S-nitrosothiols.
AB  - The nitrosation of cellular thiols has attracted much interest as a regulatory
      mechanism that mediates some of the pathophysiological effects of nitric oxide
      (NO). In cells, virtually all enzymes contain cysteine residues that can be
      subjected to S-nitrosation, whereby this process often acts as an activity
      switch. Nitrosation of biological thiols is believed to be mediated by N2O3,
      metal-nitrosyl complexes, and peroxynitrite. To date, however, enzymatic pathways
      for S-denitrosation of proteins have not been identified. Herein, we present
      experimental evidence that two ubiquitous cellular dithiols, thioredoxin and
      dihydrolipoic acid, catalyze the denitrosation of S-nitrosoglutathione, S
      nitrosocaspase 3, S-nitrosoalbumin, and S-nitrosometallothionenin to their
      reduced state with concomitant generation of nitroxyl (HNO), the one-electron
      reduction product of NO. In these reactions, formation of NO and HNO was assessed
      by ESR spectrometry, potentiometric measurements, and quantification of
      hydroxylamine and sodium nitrite as end reaction products. Nitrosation and
      denitrosation of caspase 3 was correlated with its proteolytic activity. We also
      report that thioredoxin-deficient HeLa cells with mutated thioredoxin reductase
      denitrosate S-nitrosothiols less efficiently. We conclude that both thioredoxin
      and dihydrolipoic acid may be involved in the regulation of cellular S
      nitrosothiols.

PMID- 16277525
TI  - Mild palladium-catalyzed selective monoarylation of nitriles.
AB  - Two new palladium-catalyzed procedures for the arylation of nitriles under less
      basic conditions than previously reported have been developed. The selective
      monoarylation of acetonitrile and primary nitriles has been achieved using alpha
      silyl nitriles in the presence of ZnF2. This procedure is compatible with a
      variety of functional groups, including cyano, keto, nitro, and ester groups, on
      the aryl bromide. The arylation of secondary nitriles occurred in high yield by
      conducting reactions with zinc cyanoalkyl reagents. These reaction conditions
      tolerated base-sensitive functional groups, such as ketones and esters. The
      combination of these two methods, one with alpha-silyl nitriles and one with zinc
      cyanoalkyl reagents, provides a catalytic route to a variety of benzylic
      nitriles, which have not only biological significance but utility as synthetic
      intermediates. The utility of these new coupling reactions has been demonstrated
      by a synthesis of verapamil, a clinically used drug for the treatment of heart
      disease, by a three-step route from commercial materials that allows convenient
      variation of the aryl group.

PMID- 16277526
TI  - Marked dependence on carrier-ligand bulk but not on carrier-ligand chirality of
      the duplex versus single-strand forms of a DNA oligonucleotide with a series of G
      Pt(II)-G intrastrand cross-links modeling cisplatin-DNA adducts.
AB  - The N7-Pt-N7 adjacent G,G intrastrand DNA cross-link responsible for cisplatin
      anticancer activity is dynamic, promotes local "melting" in long DNA, and
      converts many oligomer duplexes to single strands. For 5'
      d(A1T2G3G4G5T6A7C8C9C10A11T12)-3' (G3), treatment of the (G3)2 duplex with five
      pairs of [LPt(H2O)2]2+ enantiomers (L = an asymmetric diamine) formed mixtures of
      LPt-G3 products (1 Pt per strand) cross-linked at G3,G4 or at G4,G5 in all cases.
      L chirality exerted little influence. For primary diamines L with bulk on chelate
      ring carbons (e.g., 1,2-diaminocyclohexane), the duplex was converted completely
      into single strands (G3,G4 coils and G4,G5 hairpins), exactly mirroring results
      for cisplatin, which lacks bulk. In sharp contrast, for secondary diamines L with
      bulk on chelate ring nitrogens (e.g., 2,2'-bipiperidine, Bip), unexpectedly
      stable duplexes having two platinated strands (even a unique G3,G4/G4,G5
      heteroduplex) were formed. After enzymatic digestion of BipPt-G3 duplexes, the
      conformation of the relatively nondynamic G,G units was shown to be head-to-head
      (HH) by HPLC/mass spectrometric characterization. Because the HH conformation
      dominates at the G,G lesion in duplex DNA and in the BipPt-G3 duplexes, the
      stabilization of the duplex form only when the L nitrogen adducts possess bulk
      suggests that H-bonding interactions of the Pt-NH groups with the flanking DNA
      lead to local melting and to destabilization of oligomer duplexes. The marked
      dependence of adduct properties on L bulk and the minimal dependence on L
      chirality underscore the need for future exploration of the roles of the L
      periphery in affecting anticancer activity.

PMID- 16277527
TI  - Biomimetic anchor for surface-initiated polymerization from metal substrates.
AB  - In this paper, we demonstrate the first use of a catecholic initiator for surface
      initiated polymerization (SIP) from metal surfaces to create antifouling polymer
      coatings. A new bifunctional initiator inspired by mussel adhesive proteins was
      synthesized, which strongly adsorbs to Ti and 316L stainless steel (SS)
      substrates, providing an anchor for surface immobilization of grafted polymers.
      Surface-initiated atom transfer radical polymerization (SI-ATRP) was performed
      through the adsorbed biomimetic initiator to polymerize methyl methacrylate
      macromonomers with oligo(ethylene glycol) (OEG) side chains. X-ray photoelectron
      spectroscopy, surface FT-IR, and contact angle analysis confirmed the sequential
      grafting of initiator and polymer, and ellipsometry indicated the formation of
      polymer coatings of up to 100 nm thickness. Cell adhesion experiments performed
      with 3T3-Swiss albino fibroblasts showed substantially reduced cell adhesion onto
      polymer grafted Ti and 316L SS substrates as compared to the unmodified metals.
      Moreover, micropatterning of grafted polymer coatings on Ti surfaces was
      demonstrated by combining SI-ATRP and molecular assembly patterning by lift-off
      (MAPL), creating cell-adhesive and cell-resistant regions for potential use as
      cell arrays. Due to the ability of catechols to bind to a large variety of
      inorganic surfaces, this biomimetic anchoring strategy is expected to be a highly
      versatile tool for polymer thin film surface modification for biomedical and
      other applications.

PMID- 16277528
TI  - Synergy of intramolecular hydrogen-bonding network in myo-inositol 2
      monophosphate: theoretical investigations into the electronic structure, proton
      transfer, and pKa.
AB  - This work demonstrates the pivotal role that an intramolecular hydrogen-bonding
      network (intra-HBN) plays in the determination of the conformation of myo
      inositol 2-monophosphate (Ins(2)P1), a member of the inositol phosphate family of
      compounds, which are important participants in the role that phosphates play in
      biological and environmental chemistry. For biologically significant compounds
      that contain phosphate and hydroxyl groups, Ins(2)P1 is a model system for
      studying both the primary forces that determine their conformations and their
      chemical properties from the effect of phosphate group addition. We performed ab
      initio calculations to determine the intra-HBN within important thermally
      accessible conformations for neutral Ins(2)P1 and its anions, Ins(2)P1(1-) and
      Ins(2)P1(2-). The results show that the global minima prefer 1a/5e structures
      where the phosphate group is in the axial position with all -OH groups in the
      equatorial positions. The calculations of transition state structures for ring
      inversion at each ionization state predict an activation energy of 18.16 kcal/mol
      for the neutral species in water, while the activation energy is lower for the
      charged compounds, 15.62 kcal/mol for Ins(2)P1(1-) and 12.48 kcal/mol for
      Ins(2)P1(2-). The pK(a) values of Ins(2)P1 were calculated by modeling the
      solvent as a polarizable continuum medium (PCM) and as explicit solvent
      molecules. These values are in good agreement with experimental data. A novel
      four-center pattern of hydrogen bonding was found to stabilize the system. The
      intramolecular proton transfer across a low barrier hydrogen bond between the
      charged phosphate and hydroxyl groups was found to occur under standard
      conditions with an activation energy that is less than 0.5 kcal/mol.

PMID- 16277529
TI  - Molecular umbrella-assisted transport of an oligonucleotide across cholesterol
      rich phospholipid bilayers.
AB  - A series of molecular umbrella conjugates, derived from cholic acid, deoxycholic
      acid, spermidine, lysine, and 5-mercapto-2-nitrobenzoic acid, have been
      synthesized and found capable of transporting an attached 16-mer oligonucleotide
      (S-dT16) across liposomal membranes made from 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyldglycerol
      (POPG), and cholesterol [POPC/POPG/cholesterol (65/5/30; mol/mol/mol, v/v/v)] at
      37 degrees C. Those molecular umbrellas containing four choloyl (or deoxycholoyl)
      groups resulted in significantly faster rates of transport as compared to those
      containing only two such moieties. A model that accounts for these membrane
      transport processes is proposed.

PMID- 16277530
TI  - Autocatalytic modification of the prosthetic heme of horseradish but not
      lactoperoxidase by thiocyanate oxidation products. A role for heme-protein
      covalent cross-linking.
AB  - The mammalian peroxidases eosinophil peroxidase, lactoperoxidase (LPO), and
      myeloperoxidase oxidize thiocyanate to the antimicrobial agents hypothiocyanous
      acid (HOSCN) and (SCN)2 and are part of a defense system that protects the host
      from infections. Horseradish peroxidase (HRP), a plant enzyme, also oxidizes
      thiocyanate. We report here that the prosthetic heme vinyl groups of HRP react
      with the catalytically generated HOSCN and (SCN)2 to form at least nine vinyl
      modified heme adducts. Mass spectrometry combined with analysis of the equivalent
      reactions of HRP reconstituted with 2- or 4-cyclopropylheme, or mesoheme-d4,
      shows that all of the prosthetic heme modifications result from addition of
      oxidized thiocyanate to the heme vinyl groups. No delta-meso-substitution of the
      heme was observed, in contrast to what is observed with radical agents. Model
      studies show that incubation of either HRP with preformed HOSCN or a solution of
      heme with preformed (SCN)2 gives rise to the same products obtained in the HRP
      catalyzed reaction. Model studies also demonstrate that the SCN* radical, if
      formed, should add to a meso-carbon. These findings implicate an electrophilic
      addition mechanism. In contrast, oxidation by LPO of thiocyanate, the normal
      substrate of this enzyme, does not result in heme modification. In view of the
      demonstrated intrinsic reactivity of the heme group, LPO must actively suppress
      heme modification. As the key difference between LPO (and other mammalian
      peroxidases) and HRP is the presence of two covalent ester links between the heme
      and the protein, we propose that these links contribute to steric protection of
      the adjacent heme vinyl groups.

PMID- 16277531
TI  - Electron inventory, kinetic assignment (E(n)), structure, and bonding of
      nitrogenase turnover intermediates with C2H2 and CO.
AB  - Improved 1H ENDOR data from the S(EPR1) intermediate formed during turnover of
      the nitrogenase alpha-195Gln MoFe protein with C2(1,2)H2 in (1,2)H2O buffers,
      taken in context with the recent study of the intermediate formed from propargyl
      alcohol, indicate that S(EPR1) is a product complex, likely with C2H4 bound as a
      ferracycle to a single Fe of the FeMo-cofactor active site. 35 GHz CW and Mims
      pulsed 57Fe ENDOR of 57Fe-enriched S(EPR1) cofactor indicates that it exhibits
      the same valencies as those of the CO-bound cofactor of the lo-CO intermediate
      formed during turnover with CO, [Mo4+, Fe3+, Fe6(2+), S9(2-)(d43)](+1), reduced
      by m = 2 electrons relative to the resting-state cofactor. Consideration of 57Fe
      hyperfine coupling in S(EPR1) and lo-CO leads to a picture in which CO bridges
      two Fe of lo-CO, while the C2H4 of S(EPR1) binds to one of these. To correlate
      these and other intermediates with Lowe-Thorneley (LT) kinetic schemes for
      substrate reduction, we introduce the concept of an "electron inventory". It
      partitions the number of electrons a MoFe protein intermediate has accepted from
      the Fe protein (n) into the number transmitted to the substrate (s), the number
      that remain on the intermediate cofactor (m), and the additional number delivered
      to the cofactor from the P clusters (p): n = m + s - p (with p = 0 here). The
      cofactors of lo-CO and S(EPR1) both are reduced by m = 2 electrons, but the
      intermediates are not at the same LT reduction stage (E(n)): (n = 2; m = 2, s =
      0) for lo-CO; (n = 4; s = 2, m = 2) for S(EPR1). This is the first proposed
      correlation of an LT E(n) kinetic state with a well-defined chemical state of the
      enzyme.

PMID- 16277532
TI  - A multi-mode-driven molecular shuttle: photochemically and thermally reactive
      azobenzene rotaxanes.
AB  - The shuttling process of alpha-CyD in three rotaxanes (1-3) containing alpha
      cyclodextrin (alpha-CyD) as a ring, azobenzene as a photoactive group, viologen
      as an energy barrier for slipping of the ring, and 2,4-dinitrobenzene as a
      stopper was investigated. The trans-cis photoisomerization of 1 by UV light
      irradiation occurred in both DMSO and water due to the movement of alpha-CyD
      toward the ethylene group, while the photoisomerization of 2 occurred in DMSO,
      but not in water. No photoisomerization was observed for 3 in both water and
      DMSO. The activation parameters of 1 and 1-ref in DMSO are subject to a
      compensation relation between deltaS(double dagger) and deltaH(double dagger);
      however, in water, the deltaS(double dagger) terms are not compensated by the
      deltaH(double dagger) terms. Alternating irradiation of the UV and visible lights
      resulted in a reversible change in the induced circular dichroism (ICD) bands of
      trans-1 and cis-1. In contrast, after the UV light irradiation, the ICD band of
      trans-2 decreased without the appearance of any bands of cis-2. The NMR spectra
      of 2 in DMSO showed coalescence of the split signals for the methylene and for
      the viologen protons due to the shuttling of alpha-CyD. Both the NOE differential
      spectra for cis-1 in water after UV light irradiation and 2 in DMSO after heating
      to 120 degrees C showed the negative NOE peaks assigned to interior protons of
      alpha-CyD, suggesting that alpha-CyD in cis-1 exists at the one ethylene moiety,
      and alpha-CyDs in cis-2 and 2 heated in DMSO exist at the propylene moieties.

PMID- 16277533
TI  - Oxoselenido clusters of the lanthanides: rational introduction of oxo ligands and
      near-IR emission from Nd(III).
AB  - Reactions of Ln(SePh)3 with SeO2 in THF give octanuclear oxoselenido clusters
      with the general formula (THF)8Ln8O2Se2(SePh)16 (Ln = Ce, Pr, Nd, Sm). In this
      isomorphous series, the eight Ln(III) ions are connected in the center by a pair
      of mu3-O2- ligands and mu5-Se2- ligands, with 14 bridging and two terminal
      selenolate ligands capping the cluster surface. Thermal decomposition at 700
      degrees C of the Nd compound in vacuo led to the formation of a phase mixture of
      NdSe2, Nd2Se3, and Nd2O3. Near-IR emission experiments on the
      (THF)8Nd8O2Se2(SePh)16 and the fluorinated thiolate compound (DME)2Nd(SC6F5)3
      demonstrate that clusters with oxo ligands are not only highly emissive, but also
      they emit at wavelengths not found in conventional oxides.

PMID- 16277535
TI  - Potential dependent organization of water at the electrified metal-liquid
      interface.
AB  - In situ infrared visible sum frequency generation spectroscopy (SFG) is used to
      examine the structure of water at the Ag-water interface in NaF and KF
      electrolyte solutions. Water is observed in environments associated with both the
      electrode surface and the diffuse double layer. Peaks are observed that are
      correlated with low-order water, water interacting with electrolyte ions,
      specifically adsorbed water to the electrode surface, and hydronium. Spectra
      obtained from a thiol-modified Ag surface enabled discrimination between surface
      bound water and that in the double layer. The water organization is dependent on
      applied potential, with the observed intensities for specifically adsorbed and
      ion solvating water diminishing near the pzc.

PMID- 16277534
TI  - Picosecond photoreduction of inducible nitric oxide synthase by rhenium(I)
      diimine wires.
AB  - In a continuing effort to unravel mechanistic questions associated with
      metalloenzymes, we are developing methods for rapid delivery of electrons to
      deeply buried active sites. Herein, we report picosecond reduction of the heme
      active site of inducible nitric oxide synthase bound to a series of rhenium
      diimine electron-tunneling wires, [Re(CO)3LL']+, where L is 4,7
      dimethylphenanthroline and L' is a perfluorinated biphenyl bridge connecting a
      rhenium-ligated imidazole or aminopropylimidazole to a distal imidazole (F8bp-im
      (1) and C3-F8bp-im (2)) or F (F9bp (3) and C3-F9bp (4)). All four wires bind
      tightly (Kd in the micromolar to nanomolar range) to the tetrahydrobiopterin-free
      oxidase domain of inducible nitric oxide synthase (iNOSoxy). The two fluorine
      terminated wires displace water from the active site, and the two imidazole
      terminated wires ligate the heme iron. Upon 355-nm excitation of iNOSoxy
      conjugates with 1 and 2, the active site Fe(III) is reduced to Fe(II) within 300
      ps, almost 10 orders of magnitude faster than the naturally occurring reduction.

PMID- 16277536
TI  - Stereoelectronic and steric effects in the collagen triple helix: toward a code
      for strand association.
AB  - Collagen is the most abundant protein in animals. The protein consists of a helix
      of three strands, each with sequence X-Y-Gly. Natural collagen is most stable
      when X is (2S)-proline (Pro) and Y is (2S,4R)-4-hydroxyproline (4R-Hyp). We had
      shown previously that triple helices in which X is (2S,4S)-4-fluoroproline (4S
      Flp) or Y is (2S,4R)-4-fluoroproline (4R-Flp) display hyperstability. This
      hyperstability arises from stereoelectronic effects that preorganize the main
      chain dihedral angles in the conformation found in the triple helix. Here, we
      report the synthesis of strands containing both 4S-Flp in the X-position and 4R
      Flp in the Y-position. We find that these strands do not form a stable triple
      helix, presumably because of an unfavorable steric interaction between fluoro
      groups on adjacent strands. Density functional theory calculations indicate that
      (2S,3S)-3-fluoroproline (3S-Flp), like 4S-Flp, should preorganize the main chain
      properly for triple-helix formation but without a steric conflict. Synthetic
      strands containing 3S-Flp in the X-position and 4R-Flp in the Y-position do form
      a triple helix. This helix is, however, less stable than one with Pro in the X
      position, presumably because of an unfavorable inductive effect that diminishes
      the strength of the interstrand 3S-FlpC=O...H-NGly hydrogen bond. Thus, other
      forces can counter the benefits derived from the proper preorganization. Although
      (Pro-Pro-Gly)7 and (4S-Flp-4R-Flp-Gly)7 do not form stable homotrimeric helices,
      mixtures of these two peptides form stable heterotrimeric helices containing one
      (Pro-Pro-Gly)7 strand and two (4S-Flp-4R-Flp-Gly)7 strands. This stoichiometry
      can be understood by considering the cross sections of the two possible
      heterotrimeric helices. This unexpected finding portends the development of a
      "code" for the self-assembly of determinate triple helices from two or three
      strands.

PMID- 16277537
TI  - O2 and CO binding properties of artificial hemoproteins formed by complexing iron
      protoporphyrin IX with human serum albumin mutants.
AB  - The binding properties of O2 and CO to recombinant human serum albumin (rHSA)
      mutants with a prosthetic heme group have been physicochemically and kinetically
      characterized. Iron(III) protoporphyrin IX (hemin) is bound in subdomain IB of
      wild-type rHSA [rHSA(wt)] with weak axial coordination by Tyr-161. The reduced
      ferrous rHSA(wt)-heme under an Ar atmosphere exists in an unusual mixture of four
      and five-coordinate complexes and is immediately autoxidized by O2. To confer O2
      binding capability on this naturally occurring hemoprotein, a proximal histidine
      was introduced into position Ile-142 or Leu-185 by site-directed mutagenesis. A
      single mutant (I142H) and three double mutants (I142H/Y161L, I142H/Y161F, and
      Y161L/L185H) were prepared. Both rHSA(I142H/Y161L)-heme and rHSA(I142H/Y161F)
      heme formed ferrous five-N-coordinate high-spin complexes with axial ligation of
      His-142 under an Ar atmosphere. These artificial hemoproteins bind O2 at room
      temperature. Mutation at the other side of the porphyrin, Y161L/L185H, also
      allowed O2 binding to the heme. In contrast, the single mutant rHSA(I142H)-heme
      could not bind O2, suggesting that removal of Y161 is necessary to confer
      reversible O2 binding. Laser flash photolysis experiments showed that the
      kinetics of CO recombination with the rHSA(mutant)-heme were biphasic, whereas O2
      rebinding exhibited monophasic kinetics. This could be due to the two different
      geometries of the axial imidazole coordination arising from the two orientations
      of the porphyrin plane in the heme pocket. The O2 binding affinities of the
      rHSA(mutant)-heme were significantly lower than those of hemoglobin and
      myoglobin, principally due to the high O2 dissociation rates. Changing Leu-161 to
      Phe-161 at the distal side increased the association rates of both O2 and CO,
      which resulted in enhanced binding affinity.

PMID- 16277538
TI  - Micropatterning chemical oscillations: waves, autofocusing, and symmetry
      breaking.
AB  - Arrays of chemical oscillators are micropatterned by Wet Stamping. The technique
      is used to demonstrate that chemical waves can be initiated and controlled in
      oscillatory systems and that such waves can give rise to phenomena not observed
      in excitable media. Interoscillator coupling and synchronization, kinetic
      autofocusing, and twist-symmetry breaking are a consequence of the dependence of
      the oscillation phase on the local concentrations of reagents and on systems'
      geometry. Conditions under which a generic oscillatory system would exhibit such
      behaviors are determined.

PMID- 16277540
TI  - The cucurbit[n]uril family: prime components for self-sorting systems.
AB  - We determined the values of Ka for a wide range of host-guest complexes of
      cucurbit[n]uril (CB[n]), where n = 6-8, using 1H NMR competition experiments
      referenced to absolute binding constants measured by UV/vis titration. We find
      that the larger homologues--CB[7] and CB[8]--individually maintain the size,
      shape, and functional group selectivity that typifies the recognition behavior of
      CB[6]. The cavity of CB[7] is found to effectively host trimethylsilyl groups.
      Remarkably, the values of Ka for the interaction of CB[7] with adamantane
      derivatives 22-24 exceeds 10(12) M(-1)! The high levels of selectivity observed
      for each CB[n] individually is also observed for the CB[n] family collectively.
      That is, the selectivities of CB[6], CB[7], and CB[8] toward a common guest can
      be remarkably large. For example, guests 1, 3, and 11 prefer CB[8] relative to
      CB[7] by factors greater than 10(7), 10(6), and 3000, respectively. Conversely,
      guests 23 and 24 prefer CB[7] relative to CB[8] by factors greater than 5100 and
      990, respectively. The high levels of selectivity observed individually and
      collectively for the CB[n] family renders them prime components for the
      preparation of functional biomimetic self-sorting systems.

PMID- 16277539
TI  - Detection of homocysteine and cysteine.
AB  - At elevated levels, homocysteine (Hcy, 1) is a risk factor for cardiovascular
      diseases, Alzheimer's disease, neural tube defects, and osteoporosis. Both 1 and
      cysteine (Cys, 3) are linked to neurotoxicity. The biochemical mechanisms by
      which 1 and 3 are involved in disease states are relatively unclear. Herein, we
      describe simple methods for detecting either Hcy or Cys in the visible spectral
      region with the highest selectivity reported to date without using biochemical
      techniques or preparative separations. Simple methods and readily available
      reagents allow for the detection of Cys and Hcy in the range of their
      physiologically relevant levels. New HPLC postcolumn detection methods for
      biological thiols are reported. The potential biomedical relevance of the
      chemical mechanisms involved in the detection of 1 is described.

PMID- 16277541
TI  - Self-organization of bidisperse colloids in water droplets.
AB  - Most of the colloidal clusters have been produced from oil-in-water emulsions
      with identical microspheres dispersed in oil droplets. Here, we present new types
      of binary colloidal clusters from phase-inverted water-in-oil emulsions using
      various combinations of two different colloids with several size ratios:
      monodisperse silica or polystyrene microspheres for larger particles and silica
      or titania nanoparticles for smaller particles. Obviously, a better understanding
      of how finite groups of different colloids self-organize in a confined geometry
      may help us control the structure of matter at multiple length scales. In
      addition, since aqueous dispersions have much better phase stability, we could
      produce much more diverse colloidal materials from water-in-oil emulsions rather
      than from oil-in-water emulsions. Interestingly, the configurations of the large
      microspheres were not changed by the presence of the small particles. However,
      the arrangement of the smaller particles was strongly dependent on the nature of
      the interparticle interactions. The experimentally observed structural evolutions
      were consistent with the numerical simulations calculated using Surface Evolver.
      These clusters with nonisotropic structures can be used as building blocks for
      novel colloidal structures with unusual properties or by themselves as light
      scatterers, diffusers, and complex adaptive matter exhibiting emergent behavior.

PMID- 16277543
TI  - How stable is trans-cycloheptene?
AB  - There is a discrepancy between the observed and calculated stability of trans
      cycloheptene (t-CHP). Generation of t-CHP has always led to its low-temperature (
      40 degrees C) isomerization to cis-cycloheptene (c-CHP). However, force field and
      semiempirical calculations on the energy difference between the two isomers have
      suggested that t-CHP should be stable at room temperature. We performed a series
      of ab initio calculations, which predicted that the simple process of double bond
      rotation leading from t-CHP to c-CHP would have an activation barrier too high to
      permit isomerization below 100 degrees C (35 kcal/mol). The validity of our
      calculation method on this very strained system was supported by the agreement
      between the calculation and the dynamics of the ring flip of the unsymmetrical t
      CHP ring and the observed NMR shifts and coupling constants for the system. This
      incompatibility between the experimental behavior of t-CHP and our calculations
      led to our reexamining the decay kinetics of t-CHP. We find that this decay is
      second order and represents an "interrupted" dimerization, where an initially
      formed 1,4-biradical rapidly changes its geometry and cleaves back to produce two
      c-CHP molecules. This mechanism was supported by calculations of the 1,4
      biradical potential energy surface.

PMID- 16277542
TI  - Self-assembly of mercaptane-metallacarborane complexes by an unconventional
      cooperative effect: a C-H...S-H...H-B hydrogen/dihydrogen bond interaction.
AB  - The existence of a dihydrogen bond (S-H...H-B) and its combination with a C-H...S
      hydrogen bond in an unusual cooperative effect are demonstrated from a
      combination of experimental and theoretical methods. This cooperative effect
      seems to be responsible for self-assembly of mercaptane-metallacarborane
      complexes such as closo-[3-Ru(eta6-C6H6)-8-HS-1,2-C2B9H10] (1) and closo-[3
      Co(eta5-C5H5)-8-HS-1,2-C2B9H10] (3), which present identical supramolecular two
      dimensional polymeric networks. The findings, besides documenting structurally
      the first S-H...(H-B)2 dihydrogen bond and the unconventional cooperative ability
      of a boron-attached SH group, prove that substituted carboranes have the
      potential to serve as building blocks for assembling complex structures.

PMID- 16277544
TI  - Reporting pharmacoeconomic evaluations.

PMID- 16277545
TI  - Economic evaluations of healthcare programmes and decision making: the influence
      of economic evaluations on different healthcare decision-making levels.
AB  - Given the potential role of economic information in healthcare decision making,
      it is of interest to assess its influence on decisions at a national or regional
      level (macro level), at a healthcare facility level (meso level) and at the
      healthcare provider level (micro level). This literature review summarises 36
      empirical studies that examined the influence of economic evaluations on these
      three healthcare decision-making levels. Economic evaluations are considered
      useful and important; however, their direct influence on decision making
      (instrumental use) is moderate, especially at the macro and micro levels. A major
      influence was observed at the meso level, leading to the conclusion that economic
      evaluations have the most pronounced influence on decision making within
      healthcare organisations. However, unexpectedly, our literature search did not
      reveal an empirical study analysing the considerable influence of economic
      evaluations on decisions by the National Institute of Health and Clinical
      Excellence in the UK. Our findings indicate that results of economic evaluations
      cannot be considered the dominant decision criterion for healthcare decision
      makers at either the macro, meso or micro levels. Enlightenment use (where
      scientific evidence provides a background of information, ideas and concepts that
      affect the way policy makers view problems and solutions) of economic evaluations
      in decision making remains to be proven.

PMID- 16277546
TI  - Antiviral agents for influenza: a comparison of cost-effectiveness data.
AB  - The economic burden of influenza-related illness has been estimated to be 71.3
      166 billion US dollars in the US, the majority of which is attributable to
      indirect costs as a result of lost productivity. There are currently four
      antiviral drugs available for the treatment of influenza: two ion channel
      blockers, amantadine and rimantadine; and two neuraminidase inhibitors, zanamivir
      and oseltamivir. The objective of this paper was to review the studies evaluating
      the cost effectiveness of currently available antiviral treatment and prophylaxis
      management strategies for influenza. Published studies that reported both costs
      and effectiveness of influenza management were extracted using MEDLINE, pre
      MEDLINE and EMBASE. To facilitate a broad comparison, all costs were inflated to
      2003 US dollars. Fifteen studies met the inclusion criteria of the review, with
      14 analyses based on decision-analytic modelling and one economic analysis
      performed alongside a clinical trial. Management strategies included antiviral
      influenza prophylaxis or vaccination, empiric treatment of suspected disease, or
      antiviral treatment following rapid influenza testing. Study populations included
      healthy adults, adults at risk of influenza-related adverse outcomes,
      institutionalised and non-institutionalised elderly, and children. The comparator
      in all studies was standard care (i.e. over-the-counter medications only), and
      analyses were carried out from both the societal and payer perspectives. The only
      dominant strategy relative to standard care was vaccination of the
      institutionalised elderly. All other strategies in all populations were both more
      costly and more effective than standard care. Depending on the population and the
      perspective, the incremental cost-effectiveness ratios (ICERs) for antiviral
      treatment strategies ranged from 5000 US dollars/QALY for amantadine in test-and
      treat studies to >400,000 US dollars/QALY for zanamivir or oseltamivir treatment
      in children. Sensitivity analysis in all studies consistently reported a strong
      influence of the population prevalence or diagnostic accuracy of influenza on the
      cost effectiveness of all strategies. Baseline influenza prevalence varied widely
      between studies, ranging from 15% to 68%. There was also a wide variation in the
      assumption about the disutility of influenza (ranging from -0.137 to -0.983 for
      the elderly requiring hospitalisation), which also impacted the cost
      effectiveness. Given the variation in the ICERs of antiviral treatment and
      prophylaxis, the uncertainty around many model parameters, and the dynamic nature
      of influenza from year to year, one can only conclude that antiviral treatment or
      prophylaxis for influenza is likely to be more cost effective in specific
      populations at specific times during the influenza season, and during influenza
      seasons when the population prevalence reaches epidemic levels or there is
      mismatch between the vaccine and the circulating virus.

PMID- 16277549
TI  - Eliciting social preference weights for Functional Assessment of Cancer Therapy
      Lung health states.
AB  - BACKGROUND: The Functional Assessment of Cancer Therapy-Lung (FACT-L) is a
      multidimensional measure of quality of life developed for use in the evaluation
      of interventions in lung cancer. OBJECTIVE: To develop a set of utility weights
      that could be used to convert FACT-L into a single index capable of being used in
      the economic analysis of clinical trial data. METHOD: A core set of FACT-L items
      were valued in two versions of a 14-page postal survey of over 400 members of the
      UK general population. Respondents valued hypothetical FACT-L health states using
      a scale from 0 to 100 (worst to best health state). Respondents also valued their
      own health using the standard form of the EuroQol EQ-5D. Data were entered into
      an ordinary least squares regression model. RESULTS: Item weights estimated in
      regression analysis yielded values for 10 items from the FACT-L. The summary
      index based on this selected set of FACT-L items has a maximum value of 0.703 and
      a minimum value of 0.111. CONCLUSION: This study demonstrates a practical method
      of converting a standard condition-specific measure into a form that has the
      requisite properties to legitimise its use in cost-utility analysis. The
      methodology used here is not unique to FACT-L and might be considered appropriate
      for use in converting similar instruments.

PMID- 16277547
TI  - Assessing the annual economic burden of preventing and treating anogenital human
      papillomavirus-related disease in the US: analytic framework and review of the
      literature.
AB  - The anogenital human papillomavirus (HPV) is estimated to be the most commonly
      occurring sexually transmitted infection in the US. Comprehensive estimates of
      the annual economic burden associated with the prevention and treatment of
      anogenital HPV-related disease in the US population are currently unavailable.
      The purpose of this paper is to (i) outline an analytic framework from which to
      estimate the annual economic burden of preventing and treating anogenital HPV
      related disease in the US; (ii) review available US literature concerning the
      annual economic burden of HPV; and (iii) highlight gaps in current knowledge
      where further study is particularly warranted. Among eight US studies identified
      that describe the annual economic burden pertaining to one or more aspects of
      anogenital HPV-related disease, three met the review eligibility criteria
      (published between 1990 and 2004, examined multiple facets of annual anogenital
      HPV-related economic burden, and clearly articulated the data and methods used in
      the estimation process). All costs were adjusted to 2004 US dollars. Estimates of
      the annual direct medical costs associated with cervical cancer were comparable
      across studies (range 300-400 million US dollars). In contrast, there was a wide
      range across studies for estimates of the annual direct medical costs associated
      with cervical intraepithelial neoplasia (range 700 million US dollars-2.3 billion
      US dollars). Only one study reported direct medical costs for anogenital warts
      (200 million US dollars) and routine cervical cancer screening (2.3 billion US
      dollars). No studies examined direct medical costs attributable to HPV-related
      anal, penile, vaginal or vulvar cancers, or the work and productivity losses
      resulting from time spent receiving medical care, morbidity or mortality. Current
      economic burden estimates would suggest annual direct medical costs associated
      with the prevention and treatment of anogenital warts and cervical HPV-related
      disease of at least 4 billion US dollars. This figure would likely rise to at
      least 5 billion US dollars per year if direct medical costs associated with other
      disease entities caused by the sexual transmission of HPV were included, with
      further additions to the economic burden totalling in the billions of dollars if
      work and productivity losses were incorporated, a research priority for future
      studies.

PMID- 16277548
TI  - Acute pyelonephritis among adults: cost of illness and considerations for the
      economic evaluation of therapy.
AB  - Urinary tract infection (UTI) is an infection anywhere in the urinary tract, most
      commonly due to bacteria. If infection involves the kidney, the UTI is termed
      acute pyelonephritis (APN). An estimated 10-30% of all patients with APN are
      hospitalised for treatment; in the US, the incidence of hospitalisation is 11.7
      per 10,000 for women and 2.4 per 10,000 for men. Perhaps because of the generally
      good prognosis of APN when treated with current antibacterial therapies, there
      have been relatively few studies of patient management and therapeutic options
      for the disease, or of its epidemiology and risk factors. The most cost-effective
      outpatient management strategy (immediate discharge, observation followed by
      discharge, etc.) is currently unknown. Appropriate antimicrobial selection is
      clearly important, as treatment failures will increase the cost of care and
      result in additional morbidity for patients. The direct and indirect costs of APN
      are significant: an estimated 2.14 billion US dollars (year 2000 values). Cost
      estimates are most sensitive to hospitalisation rates, which are unknown in the
      US. Additional studies are needed to better define when in-hospital treatment is
      required. As the pathogens causing APN are increasingly becoming resistant to
      current therapies, not only are clinical trials in order to test the
      effectiveness of alternative therapies, but epidemiological studies to identify
      risk factors for infection with a resistant isolate and effective prevention
      strategies are required, especially among those with previous episodes of APN.

PMID- 16277550
TI  - Economic evaluation of three two-drug chemotherapy regimens in advanced non-small
      cell lung cancer.
AB  - BACKGROUND: During the 1990s, a number of new cytotoxic agents with clinically
      relevant activity in non-small-cell lung cancer (NSCLC), and with a more
      favourable therapeutic index than drugs already in use, became available. Given
      the high prices of these new drugs and the large number of patients affected, it
      is important to compare the relative benefits and costs of these treatments with
      the existing regimens before treatment policy decisions are changed. PURPOSE: An
      economic evaluation of three different regimens of chemotherapy in patients with
      advanced NSCLC was performed from the perspective of the Dutch health insurance
      system using tariffs valid for 2002. The economic evaluation was integrated into
      a phase III clinical trial in which the reference regimen cisplatin-paclitaxel
      was compared with two experimental regimens: cisplatin-gemcitabine and
      gemcitabine-paclitaxel. MATERIALS AND METHODS: Unit costs were applied to
      resource use data collected prospectively on case report forms during the trial.
      The average total (uncensored) cost per patient was determined for each of the
      treatment groups. The principal outcome measure for the economic evaluation was
      the estimated mean survival time per treatment group. This outcome was then
      incorporated into incremental cost-effectiveness ratios based on costs corrected
      for censoring. The impact of uncertainty was assessed by bootstrap techniques,
      and the analysis and interpretation of the data focused on the bivariate density
      of differences in outcomes and costs in the incremental cost-effectiveness plane.
      The final results were summarised by the derivation of cost-effectiveness
      acceptability curves. RESULTS: The estimated mean survival time was equivalent in
      the two cisplatin-based regimens with largely overlapping confidence intervals.
      There was a 99% probability that cisplatin-gemcitabine is the least costly
      regimen of the two and a 72% probability that this regimen reduces costs while at
      the same time improving survival. Compared with cisplatin-paclitaxel, the
      gemcitabine-paclitaxel regimen engendered a borderline significant reduction in
      mean survival time combined with an almost 90% probability of an increase in
      costs. CONCLUSION: The two cisplatin-based regimens are equivalent in terms of
      survival, but cisplatin-gemcitabine may reduce costs by approximately 2000 Euros
      patient compared with cisplatin-paclitaxel. Gemcitabine-paclitaxel is a dominated
      option with higher costs and a reduction in mean survival time compared with
      cisplatin-paclitaxel.

PMID- 16277551
TI  - The importance of drug adverse effects compared with seizure control for people
      with epilepsy: a discrete choice experiment.
AB  - INTRODUCTION: Antiepileptic drugs (AEDs) have been shown to reduce the severity
      and frequency of seizures for most patients. However, many patients experience
      adverse effects in order to maintain seizure control. STUDY DESIGN: A stated
      preference discrete choice experiment (DCE) was used to explore the preferences
      of people with epilepsy regarding the adverse effects and seizure control of
      AEDs. METHODS: The main adverse effects of AEDs were identified through a
      literature search and expert consultation. In addition, a national epilepsy
      patient advocacy group helped to identify important attributes and commented on
      the attributes we had already identified. The DCE included five attributes
      related to adverse effects (alopecia, nausea, skin rash, concentration effects
      and weight change) plus seizure control and cost (to estimate willingness to pay
      [WTP]). A cost attribute was included in the DCE in order to estimate people's
      WTP for changes in attribute levels. Five hundred members of a national patient
      advocacy group with a diagnosis of epilepsy were presented with pairs of
      hypothetical drug profiles with varied levels of adverse effects, seizure control
      and cost; they were then asked to indicate which drug they preferred. Questions
      were also included to collect sociodemographic data (including income) and
      information regarding experience of adverse effects and medication. The survey
      was administered via the post and the Internet. Data were analysed using a random
      effects probit model. RESULTS: A total of 148 surveys were returned. All
      attributes were significant and had the expected polarity, i.e. participants
      showed a preference for less severe adverse effects, greater seizure control and
      less cost. To achieve 100% seizure control and no adverse effects, participants
      were willing to pay 709 pounds sterlings (1105 US dollars) per month, 95% CI 451
      pounds sterlings, 1278 pounds sterlings (1 pound sterling = 1.56 US dollars, 2002
      exchange rate). Participants' WTP was significantly influenced by different
      adverse effects; for example, people with epilepsy were willing to pay only 174
      pounds sterlings (271 US dollars) per month for a drug that provided seizure
      freedom but also caused hair loss. Segmented models showed that seizure frequency
      has a significant negative impact on respondents' income levels. Also, women were
      willing to pay twice as much as men to avoid weight gain. Participants were also
      willing to trade changes in seizure control for improvements in adverse effects.
      CONCLUSION: Participants placed a high value on gaining total seizure control
      with no adverse effects. This study underlines the importance that people with
      epilepsy place on reducing adverse effects. The study also revealed how
      preferences for AEDs vary in different subgroups. Management of epilepsy is
      usually aimed at minimising seizures within a tolerable level of adverse effects.
      The present study suggests that people with epilepsy have strong preferences for
      reducing adverse effects as well as improving seizure control. These data may be
      considered useful when making medical management decisions in epilepsy.

PMID- 16277553
TI  - Epstein-Barr virus provides a new paradigm: a requirement for the immediate
      inhibition of apoptosis.
AB  - DNA viruses such as herpesviruses are known to encode homologs of cellular
      antiapoptotic viral Bcl-2 proteins (vBcl-2s), which protect the virus from
      apoptosis in its host cell during virus synthesis. Epstein-Barr virus (EBV), a
      human tumor virus and a prominent member of gamma-herpesviruses, infects primary
      resting B lymphocytes to establish a latent infection and yield proliferating,
      growth-transformed B cells in vitro. In these cells, 11 viral genes that
      contribute to cellular transformation are consistently expressed. EBV also
      encodes two vBcl-2 genes whose roles are unclear. Here we show that the genetic
      inactivation of both vBcl-2 genes disabled EBV's ability to transform primary
      resting B lymphocytes. Primary B cells infected with a vBcl-2-negative virus did
      not enter the cell cycle and died of immediate apoptosis. Apoptosis was abrogated
      in infected cells in which vBcl-2 genes were maximally expressed within the first
      24 h postinfection. During latent infection, however, the expression of vBcl-2
      genes became undetectable. Thus, both vBcl-2 homologs are essential for initial
      cellular transformation but become dispensable once a latent infection is
      established. Because long-lived, latently infected memory B cells and EBV
      associated B-cell lymphomas are derived from EBV-infected proapoptotic germinal
      center B cells, we conclude that vBcl-2 genes are essential for the initial
      evasion of apoptosis in cells in vivo in which the virus establishes a latent
      infection or causes cellular transformation or both.

PMID- 16277552
TI  - Impaired DNA replication within progenitor cell pools promotes leukemogenesis.
AB  - Impaired cell cycle progression can be paradoxically associated with increased
      rates of malignancies. Using retroviral transduction of bone marrow progenitors
      followed by transplantation into mice, we demonstrate that inhibition of
      hematopoietic progenitor cell proliferation impairs competition, promoting the
      expansion of progenitors that acquire oncogenic mutations which restore cell
      cycle progression. Conditions that impair DNA replication dramatically enhance
      the proliferative advantage provided by the expression of Bcr-Abl or mutant p53,
      which provide no apparent competitive advantage under conditions of healthy
      replication. Furthermore, for the Bcr-Abl oncogene the competitive advantage in
      contexts of impaired DNA replication dramatically increases leukemogenesis.
      Impaired replication within hematopoietic progenitor cell pools can select for
      oncogenic events and thereby promote leukemia, demonstrating the importance of
      replicative competence in the prevention of tumorigenesis. The demonstration that
      replication-impaired, poorly competitive progenitor cell pools can promote
      tumorigenesis provides a new rationale for links between tumorigenesis and common
      human conditions of impaired DNA replication such as dietary folate deficiency,
      chemotherapeutics targeting dNTP synthesis, and polymorphisms in genes important
      for DNA metabolism.

PMID- 16277554
TI  - Underutilization of aspirin persists in US ambulatory care for the secondary and
      primary prevention of cardiovascular disease.
AB  - BACKGROUND: Despite the proven benefits of aspirin therapy in the primary and
      secondary prevention of cardiovascular disease (CVD), utilization rates of
      aspirin remain suboptimal in relation to recommendations. We studied national
      trends of aspirin use among intermediate- to high-risk patients in the US
      ambulatory care settings and compared the priority given to aspirin versus
      statins for CVD risk reduction. We also examined patient and health care provider
      contributors to the underuse of aspirin. METHODS AND FINDINGS: We used the 1993
      2003 US National Ambulatory Medical Care Survey and National Hospital Ambulatory
      Medical Care Survey to estimate aspirin use by cardiovascular risk. Physician
      noted cardiovascular diseases defined high risk. Intermediate risk was defined as
      having diabetes mellitus or multiple major risk factors. The proportion of
      patient visits in which aspirin was reported increased from 21.7% (95% confidence
      interval: 18.8%-24.6%) in 1993-1994 to 32.8% (25.2%-40.4%) in 2003 for the high
      risk category, 3.5% (2.0%-5.0%) to 11.7% (7.8%-15.7%) for visits by patients
      diagnosed with diabetes, and 3.6% (2.6%-4.6%) to 16.3% (11.4%-21.2%) for those
      with multiple CVD risk factors. Beginning in 1997-1998, statins were prioritized
      over aspirin as prophylactic therapy for reducing CVD risk, and the gaps remained
      wide through 2003. In addition to elevated CVD risk, greater aspirin use was
      independently associated with advanced age, male gender, cardiologist care, and
      care in hospital outpatient departments. CONCLUSION: Improvements in use of
      aspirin in US ambulatory care for reducing risks of CVD were at best modest
      during the period under study, particularly for secondary prevention, where the
      strongest evidence and most explicit guidelines exist. Aspirin is more underused
      than statins despite its more favorable cost-effectiveness. Aggressive and
      targeted interventions are needed to enhance provider and patient adherence to
      consensus guidelines for CVD risk reduction.

PMID- 16277557
TI  - Motifs, control, and stability.

PMID- 16277556
TI  - An ideal society? Neighbors of diverse origins interact to create and maintain
      complex mini-organs in the skin.

PMID- 16277559
TI  - The cell nucleus and aging: tantalizing clues and hopeful promises.

PMID- 16277558
TI  - Linking biodiversity conservation and livelihoods in India.

PMID- 16277560
TI  - Jump-starting a cellular world: investigating the origin of life, from soup to
      networks.

PMID- 16277561
TI  - Scientific longevity.

PMID- 16277563
TI  - Biological monitoring of solar UV radiation at 17 sites in Asia, Europe and South
      America from 1999 to 2004.
AB  - A small and robust dosimeter for determining the biologically effective dose of
      ambient UV radiation has been developed using UV-sensitive mutant spores of
      Bacillus subtilis strain TKJ6312. A membrane filter with four spots of the spores
      was snapped to a slide mount. The slide was wrapped and covered with two or more
      layers of polyethylene sheet to protect the sample from rain and snow and to
      reduce monthly-cumulative doses within the measurable range. From 1999, monthly
      data were collected at 17 sites for more than 1 year, and data for 4 to 6
      consecutive years were obtained from 12 sites. Yearly total values of the spore
      inactivation dose (SID) ranged from 3200 at subarctic Oulu to 96 000 at tropical
      Denpasar, and the mean yearly values of SID exhibited an exponential dependence
      on latitude in both hemispheres with a doubling for about every 14 degrees of
      change. During the observation period, increasing trends of UV doses have been
      observed at all sites with more than 5 years of data available. Year-to-year
      variations at high and middle latitude sites are considered due mostly to
      climatic variation. At three tropical sites, negative correlations between the
      yearly doses and the column ozone amounts were observed. The results verified the
      applicability of spore dosimetry for global and long-time monitoring of solar UV
      radiation, in particular at tropical sites where no monitoring is taking place.

PMID- 16277569
TI  - Commentary on the pleasures of solving impossible problems of experimental
      physiology.
AB  - This commentary presents a series of examples of "impossible experimental
      problems" that we have encountered over the years in addressing various
      challenging questions in physiology. We aim to show how stimulating the
      challenges of physiology can be and demonstrate how our naive invocation of
      methods from disparate fields of science and engineering has led to delightful
      resolutions of physiological challenges that were utterly new to this intrepid
      interdisciplinary researcher.

PMID- 16277564
TI  - Photosensitizers derived from 132-oxo-methyl pyropheophorbide-a: enhanced effect
      of indium(III) as a central metal in in vitro and in vivo photosensitizing
      efficacy.
AB  - The effects of an additional keto group on absorption wavelength and the
      corresponding metal complexes Zn(II), Cu(II) In(III) on singlet oxygen production
      and photodynamic efficacy were examined among the alkyl ether analogs of
      pyropheophorbide-a. For the preparation of the desired photosensitizers, the
      methyl 13(2)-oxo-pyropheophorbide-a obtained by reacting methyl pyropheophorbide
      a with aqueous LiOH-THF was converted into a series of alkyl ether analogs. These
      compounds were evaluated for photophysical properties and in vitro (by means of
      the MTT assay and intracellular localization in RIF cells) and in vivo (in C3H
      mice implanted with RIF tumors) photosensitizing efficacy. Among the alkyl ether
      derivatives, the methyl 3-decyloxyethyl-3-devinyl-13(2)-oxo-pyropheophorbide-a
      was found to be most effective and the insertion of In(III) into this analog
      further enhanced its in vitro and in vivo photosensitizing efficacy. Fluorescence
      microscopy showed that, in contrast to the hexyl and dodecyl ether derivatives of
      HPPH (which localize in mitochondria and lysosomes, respectively), the diketo
      analogs and their In(III) complexes localized in Golgi bodies. The preliminary in
      vitro and in vivo results suggest that, in both free-base and metalated analogs,
      the introduction of an additional keto group at the five-member exocyclic ring in
      pyropheophorbide-a diminishes its photosensitizing efficacy. This may be due to a
      shift in subcellular localization from mitochondria to the Golgi bodies. The
      further introduction of In(III) enhances photoactivity, but not by shifting the
      localization of the photosensitizer.

PMID- 16277572
TI  - Bob Genco: a life in periodontology.

PMID- 16277573
TI  - Immune response: the key to bone resorption in periodontal disease.
AB  - Periodontal disease infection with oral biofilm microorganisms initiates host
      immune response and signs of periodontitis, including bone resorption. This
      review delineates some mechanisms underlying the host immune response in
      periodontal infection and alveolar bone resorption. Activated T lymphocytes have
      been historically implicated in experimental periodontal bone resorption. An
      experimental rat adoptive transfer/gingival challenge periodontal disease model
      has been demonstrated to require antigen-specific T lymphocytes and gingival
      instillation of antigen and LPS for bone resorption. Interference with
      costimulatory interactions between T cells and antigen-presenting cells abrogated
      bone resorption, further emphasizing the significance of immune response in
      periodontal disease. Receptor activator of nuclear factor kappaB ligand (RANKL),
      a critical osteoclast differentiation factor, is expressed on T lymphocytes in
      human periodontal disease as determined by immunohistochemical and confocal
      microscopic analyses. Interference with RANKL by systemic administration of
      osteoprotegerin (OPG), the decoy receptor for (and inhibitor of) RANKL, resulted
      in abrogation of periodontal bone resorption in the rat model. This finding
      indicated that T cell-mediated bone resorption is RANKL-dependent. In additional
      experiments, treatment of T cell-transferred rats with kaliotoxin (a scorpion
      venom potassium channel inhibitor) resulted in decreases in T-cell RANKL
      expression, diminished induction of RANKL-dependent osteoclastogenesis, and
      abrogation of bone resorption, implicating an important role of immune
      response/RANKL expression in osteoclastogenesis/bone resorption. In other
      experiments, adoptive transfer of antigen-specific, RANKL-expressing B cells, and
      infection with the antigen-bearing Actinobaccillus actinomycetemcomitans gave
      rise to periodontal bone resorption, indicating that B cells also have the
      capacity to mediate bone resorption, probably via RANKL expression. In humans,
      prominent T lymphocytes have been identified in periodontal disease, and diseased
      tissues showed elevated RANKL mRNA expression, as well as decreased OPG mRNA
      expression. Mononuclear cells from periodontal lesions involving T cells and B
      cells of patients induced osteoclastogenesis in vitro. In summary, a biofilm
      interface initiates immune cell infiltration, stimulating osteoclastogenesis/bone
      resorption in periodontal disease. This resorption can be ameliorated by
      inhibition of RANKL activity or by diminishing immune cell stimulation. These two
      procedures, if localized, have the potential to lead to the prevention or
      therapeutic management of periodontal disease and therefore require further
      study.

PMID- 16277574
TI  - Genetic control of the immune response in pathogenesis.
AB  - BACKGROUND: Epidemiological studies have suggested that there is a genetic
      component to susceptibility to chronic periodontitis. Studies in humans and in
      animal models have suggested that some of the important components may be
      polymorphisms in key immunological genes. METHODS: This paper summarizes
      previously published data from a mouse model in which alveolar bone loss is
      induced by oral infection with Porphyromonas gingivalis. Mice of different inbred
      immune-normal strains were used, as well as the F1 heterozygotes from crosses
      between strains. In addition, tissue expression of an array of immunological
      genes was measured in the gingiva and spleen of these mice by quantitative
      reverse transcription-polymerase chain reaction (QPCR). RESULTS: Not all strains
      of mice are susceptible to bone loss. Intercross experiments demonstrate that
      susceptibility is an inherited trait. A subset of immunological genes tested
      showed differential basal expression in the gingiva or spleens (or both). Tumor
      necrosis factor and osteoprotegerin mRNAs are more highly expressed in the
      gingiva and interleukin-1 mRNA is more highly expressed in both the gingiva and
      the spleens of susceptible mice than resistant mice. In the resistant mice,
      interleukin-15 mRNA in the gingiva and Selp mRNA in the spleen are present at
      higher levels. In the resistant mice no genes changed expression after P.
      gingivalis infection, while mRNA for interleukin-1, osteoprotegerin, and STAT6
      all increased in the susceptible mice. CONCLUSIONS: Susceptibility and resistance
      are heritable traits. Strain differences in basal mRNA expression correlate with
      differences in susceptibility. Genes that change expression in response to
      infection also correlate with differences in susceptibility.

PMID- 16277575
TI  - Biofilm formation by the periodontopathic bacteria Treponema denticola and
      Porphyromonas gingivalis.
AB  - BACKGROUND: Periodontitis develops as a result of the interaction of the host
      with subgingival plaque bacteria. Both Porphyromonas gingivalis and Treponema
      denticola are frequently associated together in these oral biofilms. METHODS: The
      molecular basis for in vitro biofilm formation was investigated for P. gingivalis
      381, T. denticola 35405, and mixtures of the two organisms using microtiter plate
      assays. In addition, the biofilms were examined following confocal laser scanning
      microscopy. RESULTS: P. gingivalis 381, but not T. denticola strains, formed
      biofilms in vitro. This property was dependent, in part, on the strain 381 fimA,
      ppk, and usp genes. Microarray and Northern blot analyses suggested that the
      expression of the ppk gene was required for maximal expression of the uspA gene.
      P. gingivalis 381 formed synergistic biofilms when incubated with T. denticola
      strains. This process was dependent upon the strain 381 rgpB and fimA genes as
      well as the T. denticola flgE and cfpA genes. CONCLUSIONS: P. gingivalis 381
      formed synergistic biofilms with T. denticola 35405. These results may be
      relevant to the previous observations that the two organisms are frequently
      observed together in subgingival plaque with the spirochetes localized to the
      exterior of the oral biofilms. It is suggested that other such synergistic
      effects may also occur between other plaque bacteria.

PMID- 16277576
TI  - Identification of a genomic island of Actinobacillus actinomycetemcomitans.
AB  - BACKGROUND: Horizontal gene transfer (HGT) is a process by which bacteria acquire
      genes from organisms of distant taxa. HGT is now recognized as a major driving
      force in the evolution of bacterial pathogens. Through this process, bacteria may
      accumulate blocks of DNA such as genomic islands (GEIs) that encode fitness or
      virulence factors. The periodontal pathogen A. actinomycetemcomitans has been
      known to exhibit variable virulence potential. It is postulated that GEIs may
      play a role in modifying the virulence potential of A. actinomycetemcomitans.
      This study was initiated to identify and determine the distribution of GEIs in A.
      actinomycetemcomitans. METHODS: Forty-seven A. actinomycetemcomitans strains of
      serotypes a through f were examined. Strain-specific variant DNA in the genomes
      of A. actinomycetemcomitans was identified by polymerase chain reaction (PCR)
      genomic mapping and sequenced to identify GEIs. The distribution of the GEIs
      among test strains of A. actinomycetemcomitans was determined by PCR analysis and
      Southern hybridization assays. RESULTS: An approximately 22 kb GEI of A.
      actinomycetemcomitans, designated AAI-1, was identified in five serotype b
      strains. The AAI-1 exhibits low %G+C and encodes proteins of phage, restriction
      modification systems, mobile elements, and other hypothetical proteins of unknown
      functions. The insertion of AAI-1 was found to cause truncation of A.
      actinomycetemcomitans genes at the insertion site. CONCLUSIONS: Some A.
      actinomycetemcomitans strains may harbor GEIs, which were acquired via HGT by the
      bacteria. The GEIs may increase the gene repertoire of A. actinomycetemcomitans.
      However, the insertion of the GEIs in A. actinomycetemcomitans may also cause
      truncation and inactivation of resident genes at the insertion sites. The
      virulence significance of such gain and loss of genes in A. actinomycetemcomitans
      remains to be determined.

PMID- 16277577
TI  - Medications: a risk factor for periodontal disease diagnosis and treatment.
AB  - Among the aging U.S. population, patients are taking significantly more
      medications than in the past. In view of this, dentists should take careful
      medical histories, including use of herbal agents, and be aware of medication
      related problems and their potential effect on the diagnosis and treatment of
      periodontal disease. This review highlights major concerns about medications as a
      risk factor for periodontal therapy. Medications and their impact on periodontal
      disease can be categorized as those which affect oral hygiene, diagnosis,
      gingival and oral mucosa, and alveolar bone.

PMID- 16277578
TI  - Periodontitis and rheumatoid arthritis: a review.
AB  - Periodontitis and rheumatoid arthritis (RA) appear to share many pathologic
      features. In this review, the common pathologic mechanisms of these two common
      chronic conditions are explored. Emerging evidence now suggests a strong
      relationship between the extent and severity of periodontal disease and RA. While
      this relationship is unlikely to be causal, it is clear that individuals with
      advanced RA are more likely to experience more significant periodontal problems
      compared to their non-RA counterparts, and vice versa. A case is made that these
      two diseases could be very closely related through common underlying dysfunction
      of fundamental inflammatory mechanisms. The nature of such dysfunction is still
      unknown. Nonetheless, there is accruing evidence to support the notion that both
      conditions manifest as a result of an imbalance between proinflammatory and anti
      inflammatory cytokines. As a result, new treatment strategies are expected to
      emerge for both diseases that may target the inhibition of proinflammatory
      cytokines and destructive proteases. The clinical implications of the current
      data dictate that patients with RA should be carefully screened for their
      periodontal status.

PMID- 16277579
TI  - A proposed model linking inflammation to obesity, diabetes, and periodontal
      infections.
AB  - BACKGROUND: Obesity is an important risk factor for diabetes, cardiovascular
      disease, and periodontal disease. Adipocytes appear to secrete proinflammatory
      cytokines which may be the molecules linking the pathogenesis of these diseases.
      We evaluated the relationship between obesity, periodontal disease, and diabetes
      mellitus insulin resistance as well as the plasma levels of tumor necrosis factor
      alpha (TNFalpha) and its soluble receptors (sTNFalpha) to assess the relationship
      of inflammation to obesity, diabetes, and periodontal infections. METHODS: The
      relationship between periodontal disease, obesity, and insulin resistance was
      examined in the Third National Health and Nutrition Examination Survey (NHANES
      III). In a population of 12,367 non-diabetic subjects, the variable body mass
      index (BMI) was used as an assessment of obesity and periodontal disease was
      assessed by mean clinical attachment loss. The plasma levels of TNFalpha and
      sTNFalpha were assessed in subsets of 1,221 adults from Erie County, New York,
      who represented the highest and lowest quartile of BMI. These subjects had
      extensive periodontal and medical evaluations. RESULTS: In the NHANES III portion
      of the study, BMI was positively related to severity of periodontal attachment
      loss (P <0.001). Weighted multiple logistic regressions showed that this
      relationship is likely mediated by insulin resistance, since overweight
      individuals (with BMI >or=27 kg/m2) with high levels of insulin resistance (IR)
      exhibited an odds ratio of 1.48 (95% confidence interval 1.13 - 1.93) for severe
      periodontal disease as compared to overweight subjects with low IR. In the Erie
      County adult population, the highest levels of TNFalpha and sTNFalpha receptors
      were found in those individuals in the highest quartile of BMI. A positive
      correlation of TNFalpha levels with periodontal disease was found only in those
      in the lowest quartile of BMI. CONCLUSIONS: Obesity is a significant predictor of
      periodontal disease and insulin resistance appears to mediate this relationship.
      Furthermore, obesity is associated with high plasma levels of TNFalpha and its
      soluble receptors, which in turn may lead to a hyperinflammatory state increasing
      the risk for periodontal disease and also accounting in part for insulin
      resistance. Further studies of the molecular basis of insulin resistance and its
      relationship to diabetes, periodontal disease, and obesity are necessary to fully
      test the hypothesis that adipocyte production of proinflammatory cytokines is a
      pathogenic factor linking obesity to diabetes and periodontal infections.

PMID- 16277580
TI  - Dental infections and cardiovascular diseases: a review.
AB  - Accumulating evidence suggests that chronic infections, such as periodontitis,
      are associated with increased risk for cardiovascular diseases (CVD). The
      mechanisms behind the association are not known. Like herpes viruses and
      Chlamydia pneumoniae, periodontal pathogens cause atherosclerosis in experimental
      animals and have been found in human atherosclerotic lesions. Higher
      concentrations of total and low density lipoprotein (LDL) cholesterol and
      triglycerides and lower concentrations of high density lipoprotein (HDL)
      cholesterol have been observed in individuals with periodontitis before
      periodontal treatment. Periodontitis also induces a peripheral inflammatory and
      immune response, reflected in elevated concentrations of C-reactive protein (CRP)
      and IgA-class antibodies to periodontal pathogens. The prevalence of CVD seems to
      be highest in those individuals in whom periodontitis coexists with elevated CRP
      levels. This may indicate that periodontitis is a CVD risk factor in individuals
      who react to the infection with a systemic inflammatory and immune response. This
      may be due to genetic reasons and may also apply to other chronic low-grade
      infections.

PMID- 16277581
TI  - Systemic effects of periodontitis: epidemiology of periodontal disease and
      cardiovascular disease.
AB  - There have been 42 published studies describing associations between oral
      conditions and cardiovascular diseases. In the absence of randomized controlled
      trials, the 16 longitudinal studies represent the highest level of evidence
      available. However, two databases produced eight of the 16 studies. There also is
      extensive variability in definitions of the oral exposure that include salivary
      flow, reported periodontal disease, number of teeth, oral organisms, antibodies
      to oral organisms, Total Dental Index, Community Periodontal Index of Treatment
      Needs, plaque scores, probing depth, attachment loss, and bone level. Variability
      also exists in the cardiovascular outcomes that include atherosclerosis measures
      and events, such as hospitalization for coronary heart disease (CHD), chronic
      CHD, fatal CHD, total stroke, ischemic stroke, and revascularization procedures.
      One of the criticisms of this research is that the exposure has not been
      represented by measures of infection. To begin to address this concern, we
      present new data showing that patterns of high and low levels of eight
      periodontal pathogens and antibody levels against those organisms are related to
      clinical periodontal disease as well as other characteristics of the individuals,
      such as age, race, gender, diabetic status, atherosclerosis, and CHD. As others
      before us, we conclude that the cumulative evidence presented above supports, but
      does not prove, a causal association between periodontal infection and
      atherosclerotic cardiovascular disease or its sequelae. A number of legitimate
      concerns have arisen about the nature of the relationship and, indeed, the
      appropriate definitions for periodontal disease when it is thought to be an
      exposure for systemic diseases. There is still much work needed to identify which
      aspects of the exposure are related to which aspects of the outcome. Principal
      component analyses illustrate the complexity of the interactions among risk
      factors, exposures, and outcomes. These analyses provide an initial clustering
      that describes and suggests the presence of specific syndromes.

PMID- 16277582
TI  - Oral streptococci and cardiovascular disease: searching for the platelet
      aggregation-associated protein gene and mechanisms of Streptococcus sanguis
      induced thrombosis.
AB  - BACKGROUND: Pathogenic mechanisms in infective endocarditis, disseminated
      intravascular coagulation, and cardiovascular events involve the aggregation of
      platelets into thrombi. Attendant infection by oral bacteria contributes to these
      diseases. We have been studying how certain oral streptococci induce platelet
      aggregation in vitro and in vivo. Streptococcus sanguis expresses a platelet
      aggregation-associated protein (PAAP), which contributes little to adhesion to
      platelets. When specific antibodies or peptides block PAAP, S. sanguis fails to
      induce platelet aggregation in vitro or in vivo. METHODS: We used subtractive
      hybridization to identify the gene encoding for PAAP. RESULTS: After subtraction
      of strain L50 (platelet aggregation-negative), four strain 133-79 specific
      sequences were characterized. Sequence agg4 encoded a putative collagen-binding
      protein (CbpA), which was predicted to contain two PAAP collagen-like octapeptide
      sequences. S. sanguis CbpA- mutants were constructed and tested for induction of
      platelet aggregation in vitro. Platelet aggregation was substantially inhibited
      when compared to the wild-type using platelet-rich plasma from the principal
      donor, but adhesion was unaffected. Other donor platelets responded normally to
      the CbpA- strain, suggesting additional mechanisms of response to S. sanguis. In
      contrast, CshA- and methionine sulfoxide reductase-negative (MsrA-) strains
      neither adhered nor induced platelet aggregation. CONCLUSIONS: CbpA was suggested
      to contribute to site 2 interactions in our two-site model of platelet
      aggregation in response to S. sanguis. Platelet polymorphisms were suggested to
      contribute to the thrombogenic potential of S. sanguis.

PMID- 16277583
TI  - Systemic markers of inflammation in periodontitis.
AB  - This literature review summarizes current knowledge on the systemic levels of
      selected markers of inflammation in periodontitis. From samples of peripheral
      blood the following cellular factors are discussed: total number of white blood
      cells, red blood cells, and thrombocytes. Further, plasma levels of acute-phase
      proteins, cytokines, and coagulation factors are reviewed. From the available
      literature it appears that the total numbers of leukocytes and plasma levels of C
      reactive protein are consistently higher in periodontitis patients compared to
      healthy controls. Numbers of red blood cells and levels of hemoglobin are lower
      in periodontitis and there is a trend towards anemia of chronic disease. Most
      systemic markers of inflammation discussed in this review are also regarded as
      predictive markers for cardiovascular diseases. Therefore, changes in these
      markers in periodontitis may be part of the explanation why periodontitis is
      associated with cardiovascular diseases and/or cerebrovascular events in
      epidemiological studies. It is hypothesized that possibly daily episodes of a
      bacteremia originating from periodontal lesions are the cause for the changes in
      systemic markers in periodontitis; the cumulative size of all periodontal lesions
      in the untreated severe patient may amount to 15 to 20 cm2.

PMID- 16277584
TI  - The association between osteoporosis and alveolar crestal height in
      postmenopausal women.
AB  - BACKGROUND: Evidence supporting an association between osteoporosis and loss of
      alveolar crestal bone is limited. This study investigated that association in a
      large cohort of postmenopausal women. METHODS: A cohort of 1,341 postmenopausal
      women aged 53 to 85 were assessed for alveolar crestal height (ACH) and bone
      density. ACH was determined from oral radiographs with subjects dichotomized by
      disease severity. Bone density was assessed by dual energy x-ray absorptiometry,
      with severity determined by worst T score measured (normal >-1.00; low -1.00 to 
      2.00; moderate -2.01 to -2.49; osteoporotic <-2.5). RESULTS: Compared to subjects
      in the normal T-score group, the odds of worse ACH increased by 39%, 59%, and
      230% for those in the low, moderate, and osteoporotic groups, respectively.
      Adjustment for weight, education, hormone use, calcium or vitamin D
      supplementation, and smoking did not appreciably change the findings. Further
      adjustment for age attenuated the association, with osteoporotic subjects having
      a 1.9-fold increase of being in the worst ACH group (95% confidence interval [CI]
      1.19 to 3.05). After age stratification, in women younger than 70 there was a
      significant trend by decreasing T-score category (P <0.02). Osteoporotic subjects
      had worse ACH (odds ratio [OR] = 1.95; 95% CI 1.20 to 3.17). In women aged 70 and
      older, worse ACH was 2.5- to 4.6-fold increased for decreasing T-score category.
      After adjustment, the OR (95% CI) for the low, moderate, and osteoporotic groups
      were 2.66 (1.12 to 6.29), 2.31 (0.89 to 6.01), and 3.57 (1.42 to 8.97),
      respectively (P trend = 0.026). CONCLUSIONS: This study found a strong and
      consistent association between T score and ACH in postmenopausal women.
      Increasing age is an important modifier of that association.

PMID- 16277585
TI  - The association between osteoporosis and oral bone loss.
AB  - BACKGROUND: Osteoporosis and osteopenia are characterized by reductions in bone
      mass and may lead to skeletal fragility and fracture. The purpose of this paper
      is to review studies to determine the relationship between oral bone loss and
      osteoporosis. In addition, the major modes of therapy for osteoporosis are
      discussed. METHODS: In this convenience review, papers studying the possible
      correlation between oral bone loss and osteoporosis in humans, written in the
      English language since 1983, were reviewed. RESULTS: The methods used to assess
      oral and systemic bone varied greatly from study to study. Therefore, the results
      were not amenable to meta-analysis. Thirteen of the 15 studies did show a
      positive correlation between systemic bone mass and oral bone mass (or bone
      loss). CONCLUSION: Studies to date indicate a possible correlation between
      systemic and oral bone loss.

PMID- 16277586
TI  - Effects of maternal Campylobacter rectus infection on murine placenta, fetal and
      neonatal survival, and brain development.
AB  - BACKGROUND: Maternal periodontal infection has been associated with increased
      risk of prematurity and low birthweight. Infection and inflammatory pathways that
      mediate prematurity have also been implicated in neonatal developmental
      impairments. The objective of this study was to determine whether maternal
      Campylobacter rectus infection that induces fetal growth restriction in a mouse
      model also compromises neonatal pup survival, growth, and neurodevelopment.
      METHODS: Timed pregnant mice were challenged with C. rectus on gestation day 7.5.
      One group of animals was sacrificed on embryonic day 16.5 for placental histology
      and measurement of fetal brain mRNA expression of tumor necrosis factor (TNF)
      alpha and interferon (IFN)-gamma. Another group of animals was allowed to deliver
      to follow pup survival, growth, and brain structure at day 9. RESULTS: C. rectus
      challenge resulted in abnormal placental architecture with inflammation and a 2.8
      fold increase in fetal brain expression of IFN-gamma (P = 0.04). Pup birthweight
      was unaffected by C. rectus exposure, but lethality was 3.9-fold higher after 1
      week. Ultrastructurally, the 9-day neonatal brain tissue displayed cellular and
      myelin alterations consistent with white matter damage. CONCLUSIONS: Maternal C.
      rectus infection induces placental inflammation and decidual hyperplasia as well
      as concomitant increase in fetal brain IFN-gamma. Maternal infection increased
      pup mortality, and preliminary findings demonstrate ultrastructural changes in
      the hippocampal region of the neonatal brain, in a manner analogous to the
      effects of maternal infection on white matter damage seen in humans. Thus, the
      threat of maternal oral infectious exposure during pregnancy may not be limited
      to the duration of gestation, but may also potentially affect perinatal
      neurological growth and development.

PMID- 16277587
TI  - Periodontal therapy reduces the rate of preterm low birth weight in women with
      pregnancy-associated gingivitis.
AB  - BACKGROUND: One hypothesis to explain the association between periodontal disease
      (PD) preterm/low birth weight (PT/LBW) is that PT/LBW may be indirectly mediated
      through translocation of bacteria or bacterial products in the systemic
      circulation. Transient bacteremias occur in subjects with marginal periodontitis
      or with gingivitis, and it is possible that bacteria and their products may reach
      the placental membranes hematogenously and provide the inflammatory effect to
      induce preterm labor. The effect of gingivitis as a potential risk factor for
      PT/LBW has still not been studied. A randomized controlled trial was undertaken
      to determine the effect of routine plaque control and scaling on the pregnancy
      outcomes in women with gingivitis. METHODS: Eight hundred seventy (870) pregnant
      women with gingivitis, aged 18 to 42, were enrolled while receiving prenatal care
      in Santiago, Chile. Women were randomly assigned in a two-to-one fashion to
      either a treatment group (N = 580), receiving periodontal treatment before 28
      weeks of gestation or to a control group (N = 290), receiving periodontal
      treatment after delivery. Periodontal therapy consisted of plaque control,
      scaling, and daily rinsing with 0.12% clorhexidine. Maintenance therapy was
      provided every 2 to 3 weeks until delivery, and consisted of oral hygiene
      instruction and supragingival plaque removal by instrumentation, as needed. The
      primary outcomes assessed were delivery at less than 37 weeks of gestation or an
      infant weighing less than 2,500 g. RESULTS: Of the 870 women enrolled, 36 women
      (27 in the treatment group and nine in the control group) were excluded from the
      analyses for different reasons. The incidence of PT/LBW in the treatment group
      was 2.14% (12/560) and in the control group, 6.71% (19/283) (odds ratio [OR]
      3.26; 95% confidence interval [CI] 1.56 to 6.83; P = 0.0009). Multivariate
      logistic regression analysis showed that, after adjusting for several known risk
      factors for PT/LBW, women with gingivitis were at a higher risk of PT/LBW than
      women who received periodontal treatment (OR 2.76; 95%CI 1.29 to 5.88; P =
      0.008). CONCLUSIONS: Periodontal treatment significantly reduced the PT/LBW rate
      in this population of women with pregnancy-associated gingivitis. Within the
      limitations of this study, we conclude that gingivitis appears to be an
      independent risk factor for PT/LBW for this population.

PMID- 16277588
TI  - Involvement of periodontopathic anaerobes in aspiration pneumonia.
AB  - Increasing evidence has linked the anaerobic bacteria forming periodontopathic
      biofilms with aspiration pneumonia in elderly persons. In experiments designed to
      eliminate the potent respiratory pathogens forming biofilms in the oral cavity,
      we have shown that the mechanical and chemical oral cleansing using povidone
      iodine effectively reduced the detection rates and numbers of methicillin
      sensitive Staphylococcus species, Streptococcus pneumoniae, and Haemophilus
      influenzae in patients scheduled to undergo oral surgery requiring endotracheal
      intubation. We confirmed the pathogenicity of periodontopathic anaerobic bacteria
      for aspiration pneumonia in an experimental mouse model. Based upon the finding
      of the coexistence of Porphyromonas gingivalis with Treponema denticola in
      chronic periodontitis lesions, we innoculated a mixed culture of P. gingivalis
      and T. denticola into the mouse trachea; the resulting infection induced
      inflammatory cytokine production and caused pneumonia. In another series of
      investigations, professional oral health care (POHC), mainly cleansing
      administered by dental hygienists once a week for 24 months to elderly persons
      requiring daily care, resulted in the reduction of the number of total anaerobes,
      Candida albicans, and Staphylococcus species and in the number of cases of fatal
      aspiration pneumonia. We also found that the POHC treatment of elderly persons
      for 6 months in the winter season reduced the salivary levels of protease,
      trypsin-like activity, and neuraminidase and also decreased the frequency of
      influenza cases.

PMID- 16277589
TI  - Periodontitis and airway obstruction.
AB  - BACKGROUND: The objective of this study was to examine the relationship between
      airway obstruction and periodontal disease. METHODS: Participants were a subset
      of 860 community- dwelling, well functioning elderly (aged 70 to 79, blacks and
      whites, males and females) selected from 2,732 participants enrolled in the
      Health, Aging, and Body Composition Study (Health ABC). The periodontal
      evaluations occurred over years 2 and 3 of the study and included four indices of
      periodontal health: plaque index (PI), gingival index (GI), probing depth (PD),
      and loss of attachment (LOA). The pulmonary evaluation took place in year 1:
      conducted according to American Thoracic Society criteria, based on the forced
      expiratory volume/forced vital capacity (FEV1/FVC) ratio and then using the
      percent of predicted FEV1 to categorize severity. RESULTS: GI (P = 0.023) and LOA
      (P = 0.009) were significantly better in participants with normal pulmonary
      function compared to those with airway obstruction after adjusting for age, race,
      gender, and field center. When stratified by smoking status and after adjusting
      for age, race, gender, center, and pack-years, there was a significant
      association between periodontal health and airway obstruction in former smokers.
      Within this group, those with normal pulmonary function had significantly better
      GI (P = 0.036) and LOA (P = 0.0003) scores than those with airway obstruction.
      All periodontal indices were elevated in smokers regardless of pulmonary status;
      however, the current smoker group was too small to detect a periodontitis effect.
      CONCLUSION: While the present cross-sectional study cannot provide direct
      inference of cause and effect, it does reveal a significant association between
      periodontal disease and airway obstruction, particularly in former smokers.

PMID- 16277591
TI  - Associations between periodontal disease and systemic disease: evaluating the
      strength of the evidence.
AB  - Much work has been published on the association between periodontal disease and
      systemic disease, including original reports, narrative reviews, systematic
      reviews, and meta-analyses. Based on the existent work, one can assign an
      evidence level and grade, using standard evidence-based criteria, to the data
      available in the four major categories of medical outcomes studied:
      cardiovascular/cerebrovascular, pregnancy, pulmonary, and diabetes. We discuss
      methodologic and conceptual problems in the study of oral-systemic associations,
      focusing as an example on the association between periodontal disease and
      cardiovascular/cerebrovascular disease. We argue that the hierarchical ranking of
      studies by levels of evidence may be misleading. In particular, while randomized
      controlled trials (RCTs) are needed to determine the efficacy of periodontal
      treatment to reduce the risk of cardiovascular events, they may be of limited
      value in determining the etiologic role of periodontal disease on coronary heart
      disease and stroke. We discuss limitations of RCTs as well as the limitations of
      currently available data from epidemiologic studies, including study design and
      confounding and misclassification errors. We conclude that well-designed
      observational studies into the associations between periodontal disease and
      systemic disease need to remain an integral component of future research efforts
      in order to fully understand such associations.

PMID- 16277592
TI  - An audit of behavioral indicators of poor welfare in kenneled dogs in the United
      Kingdom.
AB  - This survey-based study describes the prevalence and onset of behavioral
      indicators of poor welfare in dogs kenneled at United Kingdom rescue shelters. It
      describes key factors contributing to individual variation in behaviors. At 8
      rescue shelters, staff trained in the care of nonhuman animals recorded daily
      whether dogs in their care displayed each of 15 behaviors. The study originally
      involved 302 dogs; for the first 14 days, it monitored only 148 dogs daily. The
      study observed dogs for a maximum of 6 weeks from admittance, observing all 15
      behaviors at least once during the first 2 weeks (n = 148). The proportion of
      dogs observed to perform each behavior differed within the sample. The most
      commonly observed behavior (24.3% of dogs) was excessive barking. The remaining
      14 behaviors ranged from listlessness (20.3%) to repetitive tail-chasing (1.3%).
      Over the 6 weeks, the proportion observed to pace repetitively and wall bounce
      increased. The proportion who lacked appetite and displayed fear-associated
      behavior decreased. Breed differences, gender, and age partially explained
      variability in the onset and prevalence of behavioral indicators of poor welfare
      in kenneled dogs.

PMID- 16277590
TI  - Resolution of inflammation in periodontitis.
AB  - Chronic inflammatory illnesses such as diabetes, arthritis, and heart disease are
      now seen as problems that might have impacts on the periodontium, and reciprocal
      effects of periodontal diseases are being considered as factors potentially
      affecting the progression of these diseases. Successful management of the
      inflammatory disorders in the human body depends on the identification of common
      pathways that would lead to a better understanding of the disease processes and
      development of novel treatment strategies. In this review, our objective is to
      identify the inflammatory basis of periodontal disease and common inflammatory
      mechanisms underlying several disorders elsewhere in the body, with an emphasis
      on how the potential extrinsic and intrinsic control methods could be used to
      prevent or treat the harmful effects linked to inflammation.

PMID- 16277593
TI  - Rates of euthanasia and adoption for dogs and cats in Michigan animal shelters.
AB  - Estimates of canine and feline euthanasia at U.S. animal shelters--largely based
      on voluntary surveys with low response rates--make it difficult to estimate the
      population from which the euthanized animals derive. Estimates of euthanasia
      rates (animals euthanized per unit of population) have varied widely and been
      available only sporadically. This study used requirements of Michigan state law
      (Pet Shops, Dog Pounds, and Animal Shelters Act, 1969) for animal shelters to
      collect admission and discharge data for all 176 Michigan-licensed animal
      shelters. In 2003, Michigan shelters discharged 140,653 dogs: Of these, 56,972
      (40%) were euthanized; 40,005 (28%) were adopted. This annual euthanasia rate is
      2.6% of the estimated 2003 Michigan dog population. Michigan shelters discharged
      134,405 cats in 2003: 76,321 (57%) by euthanasia and (24%) by adoption. The
      estimated ratio of euthanized cats to cats who had owners was 3.1%. Small
      shelters and privately owned shelters were associated with higher adoption rates.
      Comparison with historical information from the past 10 to 20 years suggests the
      number of companion animals being euthanized in shelters has decreased and that
      progress has been made in reducing the companion animal overpopulation problem.

PMID- 16277594
TI  - Adoption of shelter dogs in a Brazilian community: assessing the caretaker
      profile.
AB  - A survey in Ibiuna, Sao Paulo, Brazil, of caregivers (owners) who adopted shelter
      dogs assessed length of ownership, proportion of male and female dogs adopted,
      and owners' characteristics. It addressed breeding, neutering, vaccination, and
      veterinary care. It used no testing to provide a good "match" between dog and
      future owner. Of adopted dogs, 58% were male. Only 36% of owners were located.
      Mean ownership length was 14.8 months (95% confidence interval = 12.4 to 17.2
      months), estimated through a survival analysis method. Of adopted dogs, 40.9%
      lived with their owners; 34.9% had died (some had lived on the streets); 15.0%
      were donated; 4.3% ran away; 3.2% were returned to the city shelter. Of
      interviewees, 57% reported no difficulties with the adoption; 23.1% cited the
      animal's illness and death as the main difficulty. For contraception, 87 owners
      (46.7%) chained dogs to prevent contact with other animals; 56.5% were against
      neutering. Reasons given were compassion (58.1%), unnecessary procedure (11.4%),
      cost (9.5%), and behavior change (4.8%). This research motivated a design for
      Ibiuna shelter dog adoption to improve the proportion of successful adoptions.

PMID- 16277595
TI  - Controllability in environmental enrichment for captive chimpanzees (Pan
      troglodytes).
AB  - This study considers the use of nonsocial environmental enrichment by captive
      chimpanzees at the Primate Foundation of Arizona. The goal was to determine
      whether a relationship existed between controllability of enrichment items by
      captive chimpanzees and frequency of use. The study measured controllability, the
      ability of nonhuman animals to alter aspects of their environment by the
      potential destructibility of the enrichment item. This study examined additional
      factors that may affect enrichment use: individual age, sex, rearing history,
      social group composition, and availability of outdoor access. The chimpanzees in
      the study used destructible items--the enrichment category with the highest level
      of controllability--more than indestructible items across all age, sex, and
      rearing classes. Thus, controllability seems to be an important factor in
      chimpanzee enrichment. Younger individuals and groups with outdoor access used
      enrichment more than did older individuals and groups with indoor-only access.
      Individual sex, rearing history, and social group composition had minimal effects
      on enrichment use. These results support the importance of control to captive
      chimpanzees and further enable captive management to customize enrichment
      programs to the needs of particular animals.

PMID- 16277596
TI  - The influence of environmental enrichment on Chinese visitor behavior.
AB  - Welfare improvements for nonhuman animals should aim to satisfy the needs of
      visitors as well as those of the animals. Little research has been conducted,
      however, and existing work is confined to zoos in developed countries. This
      article reports the behavioral responses of Chinese visitors to environmental
      enrichment improvements in a zoo enclosure. Visit, viewing, and stopping
      behaviors significantly increased at the transformed exhibit, indicating that it
      provoked greater visitor interest. Furthermore, increased intragroup behaviors
      suggested that the exhibit probably motivated visitors to interact socially. The
      positive impact of the exhibit changes supports the enrichment efforts taking
      place in zoos around the world. The changes also provide encouragement for zoos
      in developing countries such as China because greater visitor interest provides a
      strong argument and an incentive for improving welfare standards.

PMID- 16277597
TI  - Use of nonhuman primates in entertainment in Southeast Asia.

PMID- 16277601
TI  - Multiple co-transfection and co-expression of human beta-1,3-N
      acetylglucosaminyltransferase with human calreticulin chaperone cDNA in a single
      step in insect cells.
AB  - Human beta-1,3-N-acetylglucosaminyltransferase 2 (beta3GnT2) is indispensable for
      the conversion of lacto-N-triose II into lacto-N-tetraose and lacto-N
      neotetraose. In this paper, we report multiple co-transfection in a single step
      using two different human cDNAs in an insect cell, beta3GnT2 and calreticulin
      chaperone respectively. This minimized the time required to isolate stably
      expressing cell line from 12 weeks to 4 weeks and simplified the isolation
      technique to a one-step process. We tried to insert as much cDNA as possible and
      used various concentrations of two antibiotics, Blasticidin and Geneticin, at 25
      1500 microg/ml respectively during co-transfection for the selection of an
      efficiently expressing stable cell line with no adverse effects. A stably
      expressing cell line was isolated which expressed beta3GnT2 and chaperone
      simultaneously, which gave an activity of 10.1 m-units/ml compared with 6.7 m
      units/ml by a cell only carrying beta3GnT2. In this study we correlated the
      activity of beta3GnT2 with the amount of beta3GnT2 and human calreticulin cDNA in
      a stably expressing insect cell line simultaneously expressing calreticulin
      chaperone. When the amounts of chaperone and beta3GnT2 cDNA were in a rough ratio
      of 1:1, the beta3GnT2 activity was at a high level. In order to achieve better
      expression levels of beta3GnT2 with less cost and time, efficient ways have to be
      devised.

PMID- 16277600
TI  - Crystal structures of the editing domain of Escherichia coli leucyl-tRNA
      synthetase and its complexes with Met and Ile reveal a lock-and-key mechanism for
      amino acid discrimination.
AB  - aaRSs (aminoacyl-tRNA synthetases) are responsible for the covalent linking of
      amino acids to their cognate tRNAs via the aminoacylation reaction and play a
      vital role in maintaining the fidelity of protein synthesis. LeuRS (leucyl-tRNA
      synthetase) can link not only the cognate leucine but also the nearly cognate
      residues Ile and Met to tRNA(Leu). The editing domain of LeuRS deacylates the
      mischarged Ile-tRNA(Leu) and Met-tRNA(Leu). We report here the crystal structures
      of ecLeuRS-ED (the editing domain of Escherichia coli LeuRS) in both the apo form
      and in complexes with Met and Ile at 2.0 A, 2.4 A, and 3.2 A resolution
      respectively. The editing active site consists of a number of conserved amino
      acids, which are involved in the precise recognition and binding of the
      noncognate amino acids. The substrate-binding pocket has a rigid structure which
      has an optimal stereochemical fit for Ile and Met, but has steric hindrance for
      leucine. Based on our structural results and previously available biochemical
      data, we propose that ecLeuRS-ED uses a lock-and-key mechanism to recognize and
      discriminate between the amino acids. Structural comparison also reveals that all
      subclass Ia aaRSs share a conserved structure core consisting of the editing
      domain and conserved residues at the editing active site, suggesting that these
      enzymes may use a common mechanism for the editing function.

PMID- 16277602
TI  - Cloning of a D-serine-regulated transcript dsr-2 from rat cerebral neocortex.
AB  - D-serine is now considered to be an endogenous co-agonist of the NMDA receptor in
      mammalian brain. To obtain insight into the molecular mechanisms underlying D
      serine metabolism and function, we explored transcripts that are responsive to D
      serine in the neocortex of the 8-day-old infant rat by a differential cloning
      technique, RNA arbitrarily primed PCR. We isolated a novel D-serine inducible
      transcript, D-serine-responsive transcript-2 (dsr-2), that was exclusively
      expressed in the brain. Sequence analysis of the corresponding cDNAs to the
      transcript revealed that the dsr-2 mRNA consists of 7199 nucleotides with an open
      reading frame encoding 111 amino acids. The dsr-2 gene was located on the reverse
      strand within an intron of the neurexin-3alpha gene, mapped to rat chromosome
      6q24-31. The regional distribution of the basal expression of dsr-2 and its
      ontogenic changes in the brain closely correlated with those of free D-serine and
      of NMDA receptor R2B subunit mRNA, but were somewhat different from those of the
      neurexin-3alpha transcript. These findings suggest that dsr-2 may be involved in
      D-serine metabolism and/or function, and in the interactions between D-serine,
      NMDA receptor and neurexin-3alpha, in mammalian brain.

PMID- 16277603
TI  - Defective calcium homeostasis in the cerebellum in a mouse model of Niemann-Pick
      A disease.
AB  - We recently demonstrated that calcium homeostasis is altered in mouse models of
      two sphingolipid storage diseases, Gaucher and Sandhoff diseases, owing to
      modulation of the activities of a calcium-release channel (the ryanodine
      receptor) and of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA)
      respectively, by the accumulating sphingolipids. We now demonstrate that calcium
      homeostasis is also altered in a mouse model of Niemann-Pick A disease, the acid
      sphingomyelinase (A-SMase)-deficient mouse (ASM-/-), with reduced rates of
      calcium uptake via SERCA in the cerebellum of 6-7-month-old mice. However, the
      mechanism responsible for defective calcium homeostasis is completely different
      from that observed in the other two disease models. Thus, levels of SERCA
      expression are significantly reduced in the ASM-/- cerebellum by 6-7 months of
      age, immediately before death of the mice, as are levels of the inositol 1,4,5
      triphosphate receptor (IP3R), the major calcium-release channel in the
      cerebellum. Systematic analyses of the time course of loss of SERCA and IP3R
      expression revealed that loss of the IP3R preceeded that of SERCA, with
      essentially no IP3R remaining by 4 months of age, whereas SERCA was still present
      even after 6 months. Expression of zebrin II (aldolase C), a protein found in
      about half of the Purkinje cells in the adult mouse cerebellum, was essentially
      unchanged during development. We discuss possible pathological mechanisms related
      to calcium dysfunction that may cause Purkinje cell degeneration, and as a
      result, the onset of neuropathology in Niemann-Pick A disease.

PMID- 16277604
TI  - Identification of the isoforms of Ca2+/calmodulin-dependent protein kinase II and
      expression of brain-derived neurotrophic factor mRNAs in the substantia nigra.
AB  - Ca2+/calmodulin-dependent protein kinase (CaMK)II is highly expressed in the CNS
      and mediates activity-dependent neuronal plasticity. Four CaMKII isoforms, alpha,
      beta, gamma and delta, have a large number of splicing variants. Here we
      identified isoforms of CaMKII in the rat substantia nigra (SN). Northern blot and
      RT-PCR analyses revealed that the gamma and delta isoform mRNAs with several
      splicing variants were predominantly expressed in SN. Immunoblot analysis
      indicated that the major isoforms were gammaA, gammaC, delta1 and delta3. An
      immunohistochemical study also confirmed the preferential localization of gamma
      and delta isoforms in SN dopaminergic neurons. In dopaminergic neurons,
      immunoreactivity against anti-CaMKIIdelta1-4 antibody was detected in both
      nucleus and cytoplasm, in contrast to the predominant expression of gamma
      isoforms in the cytoplasm. Furthermore, we showed expression of brain-derived
      neurotrophic factor (BDNF) mRNAs with exons II and IV in SN. Taken together with
      our previous observations, the results suggest that the CaMKIIdelta3 isoform is
      involved in the expression of BDNF in the SN.

PMID- 16277605
TI  - Sustained activation of metabotropic glutamate receptor 5 and protein tyrosine
      phosphatases mediate the expression of (S)-3,5-dihydroxyphenylglycine-induced
      long-term depression in the hippocampal CA1 region.
AB  - Previous studies have shown that brief application of group I metabotropic
      glutamate receptor (mGluR) agonist (S)-3, 5-dihydroxyphenylglycine (DHPG) to
      hippocampal slices can induce a chemical form of long-term depression (DHPG-LTD)
      in the hippocampal CA1 region; however, the expression mechanisms of this LTD
      remain unclear. We show here that the expression of DHPG-LTD can be specifically
      reversed by application of the broad-spectrum mGluR antagonists, (S)-alpha-methyl
      4-carboxyphenylglycine (MCPG) and LY341495, and mGluR5 antagonist, 2-methyl-6
      (phenylethyl)pyridine, but not by NMDA receptor antagonist, D-2-amino-5
      phosphonopentanoic acid, mGluR1 antagonist, LY367385, group II mGluR antagonist,
      (2S)-alpha-ethylglutamic acid, or group III mGluR antagonist, (S)-2-amino-2
      methyl-4-phosphonobutanic acid (MAP4). In addition, the ability of MCPG to
      reverse DHPG-LTD was mimicked by the protein tyrosine phosphatase inhibitors,
      phenylarsine oxide and orthovanadate, but not phospholipase C inhibitor, U73122,
      protein kinase C inhibitor, bisindolylmaleimide 1, p38 mitogen-activated protein
      kinase inhibitor, SB203580, or protein phosphatases 1/2 A inhibitor, okadaic
      acid. Moreover, MCPG reversed the DHPG-LTD without affecting the paired-pulse
      facilitation. The expression of DHPG-LTD was associated with the reduction of
      both tyrosine phosphorylation and surface expression of AMPA receptor GluR2
      subunits. Together, these results suggest that sustained activation of mGluR5 and
      in turn triggering a protein tyrosine phosphatase-dependent regulation of
      postsynaptic expression of AMPA receptors may contribute to the expression of
      DHPG-LTD.

PMID- 16277607
TI  - The zinc-finger protein ZFR is critical for Staufen 2 isoform specific
      nucleocytoplasmic shuttling in neurons.
AB  - In mammalian neurons, transport and translation of mRNA to individual potentiated
      synapses is believed to occur via a heterogeneous population of RNA granules. To
      identify components of Staufen2-containing granules, we used the yeast two-hybrid
      system. A mouse fetal cDNA library was screened with the N-terminal fragment of
      Staufen2 as bait. ZFR, a three zinc finger protein, was identified as an
      interacting protein. Confocal microscopy showed that ZFR, although mainly
      nuclear, was also found in the somatodendritic compartment of primary hippocampal
      neurons where it localized as granule-like structures. Co-localization with
      Staufen2 was observed in several granules. Biochemical analyses
      (immunoprecipitation, cell fractionation) further confirmed the ZFR/Staufen2
      association. ZFR was shown to interact with at least the Staufen2(62) isoform,
      but not with Staufen1. ZFR also co-fractionated with ribosomes and Staufen2(59)
      and Staufen2(52) in a sucrose gradient. Interestingly, knockdown expression of
      ZFR through RNA interference in neurons relocated specifically the Staufen2(62),
      but not the Staufen2(59), isoform to the nucleus. Our results demonstrate that
      ZFR is a native component of Staufen2-containing granules and likely plays its
      role during early steps of RNA transport and localization. They also suggest that
      one of these roles may be linked to Staufen2(62)-containing RNA granule formation
      in the nucleus and/or to their nucleo-cytoplasmic shuttling.

PMID- 16277606
TI  - Tumor necrosis factor-alpha stimulation of calcitonin gene-related peptide
      expression and secretion from rat trigeminal ganglion neurons.
AB  - Expression of the neuropeptide calcitonin gene-related peptide (CGRP) in
      trigeminal ganglion is implicated in neurovascular headaches and
      temporomandibular joint disorders. Elevation of cytokines contributes to the
      pathology of these diseases. However, a connection between cytokines and CGRP
      gene expression in trigeminal ganglion nerves has not been established. We have
      focused on the effects of the cytokine tumor necrosis factor-alpha (TNF-alpha).
      TNFR1 receptors were found on the majority of CGRP-containing rat trigeminal
      ganglion neurons. Treatment of cultures with TNF-alpha stimulated CGRP secretion.
      In addition, the intracellular signaling intermediate from the TNFR1 receptor,
      ceramide, caused a similar increase in CGRP release. TNF-alpha caused a
      coordinate increase in CGRP promoter activity. TNF-alpha treatment activated the
      transcription factor NF-kappaB, as well as the Jun N-terminal kinase (JNK) and
      p38 mitogen-activated protein (MAP) kinase pathways. The importance of TNF-alpha
      induction of MAP kinase pathways was demonstrated by inhibiting MAP kinases with
      pharmacological reagents and gene transfer with an adenoviral vector encoding MAP
      kinase phosphatase-1 (MKP-1). We propose that selective and regulated inhibition
      of MAP kinases in trigeminal neurons may be therapeutically beneficial for
      inflammatory disorders involving elevated CGRP levels.

PMID- 16277609
TI  - Altered glycosylation of acetylcholinesterase in Creutzfeldt-Jakob disease.
AB  - Changes in the glycosylation pattern of brain proteins have been associated with
      Creutzfeldt-Jakob disease (CJD). We have investigated the glycosylation status of
      acetylcholinesterase (AChE) by lectin binding assay. Our data show that in lumbar
      CSF from definite and probable sporadic CJD cases AChE activity is lower compared
      with that in age-matched controls. We also show, for the first time, that AChE
      glycosylation is altered in CJD CSF and brain. Unlike Alzheimer's disease, in
      which an alteration in both the glycosylation and levels of AChE molecular forms
      is observed, the abnormal glycosylation of AChE in CJD appears to be unrelated to
      changes in molecular forms of this enzyme. These findings suggest that altered
      AChE glycosylation in CJD may be a consequence of the general perturbation of the
      glycosylation machinery that affects prion protein, as well as other proteins.
      The diagnostic potential of these changes remains to be explored.

PMID- 16277610
TI  - Investigation of the abundance and subunit composition of GABAA receptor subtypes
      in the cerebellum of alpha1-subunit-deficient mice.
AB  - In cerebellum, 75% of all GABAA receptors contain alpha1 subunits. Here, we
      investigated compensatory changes in GABAA receptor subunit expression and
      composition in alpha1 subunit-knockout mice. In these mice the total number of
      cerebellar GABAA receptors was reduced by 46%. Whereas the number of receptors
      containing alpha6 subunits was unchanged, the total amount of alpha6 subunits was
      significantly elevated. RT-PCR showed no increase of alpha6 mRNA levels, arguing
      against increased biosynthesis of these subunits. Elevated levels of alpha6
      subunits in alpha1 -/- mice might thus have been caused by an increased
      incorporation of unassembled alpha6 subunits, replacing alpha1 subunits in
      alpha1alpha6betagamma2 or alpha1alpha6betadelta receptors, thus rescuing alpha6
      subunits from degradation. Elevated levels of alpha3 and alpha4 subunits in the
      cerebellum of alpha1 -/- mice possibly can be explained similarly. Finally, a
      small amount of receptors containing no gamma or delta subunits was identified in
      these mice. Results suggest a total loss of GABAA receptors in cell types where
      alpha1 was the only alpha subunit expressed and a partial compensation for
      receptor loss in cell types containing other alpha subunits. Our results do not
      support a significant compensatory synthesis of other GABAA receptor subunits in
      the cerebellum of alpha1 -/- mice.

PMID- 16277611
TI  - Inhibition of D-serine accumulation in the Xenopus oocyte by expression of the
      rat ortholog of human 3'-phosphoadenosine 5'-phosphosulfate transporter gene
      isolated from the neocortex as D-serine modulator-1.
AB  - D-serine in mammalian brains has been suggested to be an endogenous co-agonist of
      the NMDA-type glutamate receptor. We have explored the molecules regulating D
      serine uptake and release from the rat neocortex cDNA library using a Xenopus
      oocyte expression system, and isolated a cDNA clone designated as dsm-1 (D-serine
      modulator-1) encoding a protein that reduces the accumulation of D-serine to the
      oocyte. dsm-1 is the rat orthologue of the human 3'-phosphoadenosine 5'
      phosphosulfate transporter 1 (PAPST1) gene. The hydropathy analysis of the
      deduced amino acid sequence of the Dsm-1 protein predicts the 10 transmembrane
      domains with a long hydrophobic stretch in the C-terminal like some amino acid
      transporters. The dsm-1 mRNA is predominantly expressed in the forebrain areas
      that are enriched with D-serine and NMDA receptors, and in the liver. The
      transient expression of dsm-1 in COS-7 cells demonstrates a partially Golgi
      apparatus-related punctuate distribution throughout the cytoplasm with a
      concentration near the nucleus. dsm-1-expressing oocytes diminishes the sodium
      dependent and -independent accumulation of D-serine and the basal levels of the
      intrinsic D-serine and increases the rate of release of the pre-loaded D-serine.
      These findings indicate that dsm-1 may, at least in part, be involved in the D
      serine translocation across the vesicular or plasma membranes in the brain, and
      thereby control the extra- and intracellular contents of D-serine.

PMID- 16277612
TI  - The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic
      activity.
AB  - Atypical antipsychotics show preferential 5-HT 2A versus dopamine (DA) D2
      receptor affinity. At clinical doses, they fully occupy cortical 5-HT2 receptors,
      which suggests a strong relationship with their therapeutic action. Half of the
      pyramidal neurones in the medial prefrontal cortex (mPFC) express 5-HT 2A
      receptors. Also, neurones excited through 5-HT 2A receptors project to the
      ventral tegmental area (VTA). We therefore hypothesized that prefrontal 5-HT 2A
      receptors can modulate DA transmission through excitatory mPFC-VTA inputs. In
      this study we used single unit recordings to examine the responses of DA neurones
      to local (in the mPFC) and systemic administration of the 5-HT 2A/2C agonist 1
      [2,5-dimethoxy-4-iodophenyl-2-aminopropane] (DOI). Likewise, using microdialysis,
      we examined DA release in the mPFC and VTA (single/dual probe) in response to
      prefrontal and systemic drug administration. The local (in the mPFC) and systemic
      administration of DOI increased the firing rate and burst firing of DA neurones
      and DA release in the VTA and mPFC. The increase in VTA DA release was mimicked
      by the electrical stimulation of the mPFC. The effects of DOI were reversed by
      M100907 and ritanserin. These results indicate that the activity of VTA DA
      neurones is under the excitatory control of 5-HT 2A receptors in the mPFC. These
      observations may help in the understanding of the therapeutic action of atypical
      antipsychotics.

PMID- 16277613
TI  - Cyclooxygenase 2 (COX-2) inhibition increases the inflammatory response in the
      brain during systemic immune stimuli.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) and inhibitors of the
      cyclooxygenase (COX) pathways are currently recommended for the prevention and
      treatment of several inflammatory diseases, including neurodegenerative
      disorders. However non-selective blockade of COX was found to have pro
      inflammatory properties, because they have the ability to alter the plasma
      glucocorticoid levels that play a critical role in the control of the innate
      immune response. The present study investigated the role of non-selective
      (ketorolac or indomethacin) or specific inhibitors of COX-1 (SC-560) and COX-2
      (NS-398) in these effects. Mice challenged systemically with the endotoxin
      lipopolysaccharide (LPS) exhibited a robust hybridization signal for numerous
      inflammatory genes in vascular-associated cells of the brain and microglia across
      the cerebral tissue. Ketorolac, indomethacin and NS-398 significantly increased
      the ability of LPS to trigger such an innate immune response at time 3 h post
      challenge, whereas SC-560 failed to change gene expression in the brain of
      animals treated with the endotoxin. These data together with the crucial role of
      COX-2-derived prostaglandin E2 (PGE2) in the increase of glucocorticoids during
      systemic immune stimuli provide evidence that inhibition of this pathway results
      in an exacerbated early innate immune reaction. This may have a major impact on
      the use of these drugs in diseases where inflammation is believed to be a
      contributing and detrimental factor.

PMID- 16277614
TI  - Differential phospholipase C activation by phenylalkylamine serotonin 5-HT 2A
      receptor agonists.
AB  - Experiments compared a series of phenethylamine hallucinogens with their
      phenylisopropylamine analogues for binding affinity and ability to stimulate
      serotonin 5-HT 2A receptor-mediated hydrolysis of phosphatidyl inositol in cells
      expressing cloned rat and human 5-HT 2A receptors. The (+/-)phenylisopropylamine
      analogues had significantly higher intrinsic activities for 5-HT 2A receptor
      mediated hydrolysis of phosphatidyl inositol compared to their phenethylamine
      analogues. With respect to the effects of the stereochemistry of the
      phenylisopropylamines, those with the (R) absolute configuration at the alpha
      carbon had higher intrinsic activities for hydrolysis of phosphatidyl inositol in
      a cell line expressing the human 5-HT 2A receptor compared to those with the (S)
      absolute configuration. In virtual docking studies comparing the (R)- and (S)
      phenylisopropylamines with their phenethylamine analogues, there were distinct
      differences in the orientations of key ligand binding domain residues that have
      been identified as important by previous mutagenesis studies. In conclusion, our
      data support the hypothesis that phenylisopropylamines have higher hallucinogenic
      potency than their phenethylamine analogues primarily because they have higher
      intrinsic activities at 5-HT 2A receptors. Although virtual ligand binding led to
      significant perturbations of certain key residues, our results emphasize the
      conclusion reached by others that overall three-dimensional structural
      microdomains within the receptor must be considered.

PMID- 16277615
TI  - NCAM140 stimulates integrin-dependent cell migration by ectodomain shedding.
AB  - The neural cell adhesion molecule (NCAM) plays a key role in neural development,
      regeneration and synaptic plasticity. This study describes a novel function of
      NCAM140 in stimulating integrin-dependent cell migration. Expression of NCAM140
      in rat B35 neuroblastoma cells resulted in increased migration toward the
      extracellular matrix proteins fibronectin, collagen IV, vitronectin, and laminin.
      NCAM-potentiated cell migration toward fibronectin was dependent on beta1
      integrins and required extracellular-regulated kinase (ERK)1/2 mitogen-activated
      protein kinase (MAPK) activity. NCAM140 in B35 neuroblastoma cells was subject to
      ectodomain cleavage resulting in a 115 kDa soluble fragment released into the
      media and a 30 kDa cytoplasmic domain fragment remaining in the cell membrane.
      NCAM140 ectodomain cleavage was stimulated by the tyrosine phosphatase inhibitor
      pervanadate and inhibited by the broad spectrum metalloprotease inhibitor GM6001,
      characteristic of a metalloprotease. Moreover, treatment of NCAM140-B35 cells
      with GM6001 reduced NCAM140-stimulated cell migration toward fibronectin and
      increased cellular attachment to fibronectin to a small but significant extent.
      These results suggested that metalloprotease-induced cleavage of NCAM140 from the
      membrane promotes integrin- and ERK1/2-dependent cell migration to extracellular
      matrix proteins.

PMID- 16277616
TI  - The inhibition of glycogen synthase kinase 3beta by a metabotropic glutamate
      receptor 5 mediated pathway confers neuroprotection to Abeta peptides.
AB  - Activation of glycogen synthase kinase 3beta (Gsk3beta) has been shown to be a
      key component in signaling pathways that underlie neurodegeneration and
      neurodegenerative disease. Conversely, inactivation of Gsk3beta by
      phosphoinositide 3-kinase (PI3K)/Akt is an important neuroprotective mechanism.
      Previous studies have shown that agonist activation of group I metabotropic
      glutamate receptors (mGluRs) can increase neuronal survival and prevent
      apoptosis. However, little is known about the signaling pathways that couple
      mGluR5 to neuroprotection. In this report, we investigated whether activation of
      the PI3K/Akt/Gsk3beta pathway, which has been shown to have an important
      neuroprotective mechanism, is required for mGluR5 activation mediated
      neuroprotection against beta-amyloid. We found that brief incubations of mouse
      hippocampal slices with (R,S)-3,5-dihydroxyphenylglycine (DHPG) resulted in
      increased phosphorylation of Akt and Gsk3beta. The PI3K inhibitors, LY294002 and
      wortmannin, blocked the DHPG-induced increased phosphorylation of Akt and
      Gsk3beta. Similar results were observed in rat primary hippocampal cultures.
      Finally, we found that the PI3K inhibitor LY294002 can block (R,S)-2-chloro-5
      hydroxyphenylglycine (CHPG) mediated neuroprotection against beta-amyloid. Thus,
      these findings suggest that mGluR5 can modulate the PI3K/Akt/Gsk3beta pathway in
      the hippocampus, and that modulation of this signaling pathway can reverse beta
      amyloid-induced neuronal toxicity.

PMID- 16277617
TI  - Human phenylethanolamine N-methyltransferase pharmacogenomics: gene re-sequencing
      and functional genomics.
AB  - Phenylethanolamine N-methyltransferase (PNMT, EC2.1.1.28) catalyzes the N
      methylation of norepinephrine to form epinephrine. As a step toward understanding
      the possible contribution of inheritance to individual variation in PNMT
      catalyzed epinephrine formation, we 're-sequenced' the entire human PNMT gene,
      including the three exons, the introns and approximately 1 kb of the 5'-flanking
      region (5'-FR), using DNA samples from 60 African-American (AA) and 60 Caucasian
      American (CA) subjects. Within the 3.5 kb re-sequenced, 18 single nucleotide
      polymorphisms (SNPs) were observed, including four non-synonymous coding SNPs
      (cSNPs) that resulted in the following alterations in encoded amino acid
      sequence: Asn9Ser, Thr98Ala, Arg112Cys and Ala175Thr. When constructs for the non
      synonymous cSNPs were transiently expressed in COS-1 cells, the Ala98 allozyme
      displayed significantly lower levels of both activity and immunoreactive protein
      (p < 0.002) than did the wild-type (WT) enzyme due, at least in part, to
      accelerated protein degradation by a proteasome-mediated process. Luciferase
      reporter gene constructs were also created for the six common PNMT 5'-FR
      haplotypes observed. Significant differences were observed among haplotypes in
      their ability to drive transcription. These observations raise the possibility of
      inherited variation in the ability to form epinephrine from norepinephrine as a
      result of variant PNMT polymorphisms and haplotypes.

PMID- 16277618
TI  - The public policy importance of the Northern Territory's Living with Alcohol
      Program, 1992-2002.

PMID- 16277619
TI  - Finding common ground in the 'two worlds of alcohol problems': when behaviour
      change succeeds.

PMID- 16277620
TI  - Evaluating national harm reduction programs.

PMID- 16277621
TI  - Qualitative research methods within the addictions.

PMID- 16277622
TI  - Is there a case for extended interventions for alcohol and drug use disorders?
AB  - AIMS: To determine whether there is evidence to support the implementation of
      extended interventions (i.e. longer than 6 months) for individuals with alcohol
      or other drug use disorders. METHODS: Literature on extended behavioral and
      pharmacotherapy interventions was reviewed, along with findings from studies of
      extended monitoring and monitoring paired with adjunctive counseling. Studies
      were identified through database searches, citations in prior reviews and
      examinations of recent volumes of relevant journals. Key terms were defined, and
      a theoretical rationale was presented for extended treatment. Several adaptive
      treatment studies that made use of stepped care or continuation protocols were
      also described. MEASUREMENTS: The primary outcomes that were considered were
      alcohol and drug use during the intervention and post-intervention follow-ups.
      Other outcomes were examined when they were included in the articles reviewed.
      FINDINGS: Most of the studies in the review provided support for the
      effectiveness of extended interventions for alcohol and drug abusers, whether the
      extended care was delivered through face-to-face contact or via the telephone.
      These findings held across all types of interventions that were examined (e.g.
      behavioral treatment, pharmacotherapy and monitoring). However, only a few
      studies directly compared extended and standard length version of the same
      intervention. New developments in addiction treatment with implications for
      extended care models were also described and discussed. CONCLUSIONS: The findings
      of the review indicate that maintaining therapeutic contact for extended periods
      of time with individuals with alcohol and other drug disorders appears to promote
      better long-term outcomes than 'treatment as usual', although more studies are
      needed that compare extended and standard versions of interventions. Achieving
      good compliance and successful disease management with extended interventions
      will probably require adaptive protocols in which the intensity of treatment can
      be adjusted up or down in response to changes in symptoms and functioning over
      time. Future directions in research on extended interventions were discussed.

PMID- 16277623
TI  - Family members of relatives with alcohol, drug and gambling problems: a set of
      standardized questionnaires for assessing stress, coping and strain.
AB  - AIMS: To describe a set of standard questionnaire measures for the assessment of
      the needs of family members of relatives with alcohol, drug or gambling problems,
      and to present evidence of their reliability and validity from a series of
      related studies. DESIGN: Includes cross-sectional and repeated-measurement
      studies. SETTING AND PARTICIPANTS: Family members affected by and concerned about
      the problem drinking or drug-taking of close relatives in treatment and non
      treatment samples in the United Kingdom (white and Sikh) and Mexico City; family
      members of untreated heavy drinkers; and family members of problem gamblers.
      MEASUREMENTS: Four measures derived from a stress-strain-coping-support model of
      alcohol, drugs and gambling problems and the family: Family Member Impact scale
      (FMI), Symptom Rating Test (SRT), Coping Questionnaire (CQ), and Hopefulness
      Hopelessness scale (HOPE). FMI, SRT and CQ assess stress, strain and coping,
      respectively. The exact role of HOPE in the model remains to be determined. The
      support component remains unmeasured. FINDINGS: Results from a number of studies
      support the internal reliability, discriminant and construct validity and
      sensitivity to change of the SRT and its two constituent scales (psychological
      and physical symptoms) and at least two subscales of the CQ (engaged and tolerant
      inactive coping). Although showing evidence of satisfactory reliability and some
      evidence of discriminant validity, further work may be required on the CQ
      withdrawal coping subscale. Evidence suggests that the FMI is reliable and valid
      and may have a factor structure that will support future research (distinguishing
      worrying behaviour from active disturbance). HOPE is a new measure showing
      promising characteristics. CONCLUSIONS: A set of standard measures is available
      for helping to assess the needs of concerned and affected family members, derived
      from an explicit model of the family in relation to excessive drinking, drug
      taking or gambling. It may have a role to play in correcting the current neglect
      of the needs of such family members, estimated to be in the region of nearly a
      million adults in Britain alone.

PMID- 16277624
TI  - The impact of the Northern Territory's Living With Alcohol program, 1992-2002:
      revisiting the evaluation.
AB  - AIMS: To evaluate the effects of the Living With Alcohol (LWA) program and the
      LWA Alcoholic Beverage Levy on alcohol-attributable deaths in the Northern
      Territory (NT) controlling for simultaneous trends in death rates from a control
      region and non-alcohol related death trends in the NT, between 1985 and 2002.
      DESIGN: The LWA program was introduced in 1992 with funding from a special NT tax
      (Levy) on beverages with greater than 3% alcohol content by volume. The Levy was
      removed in 1997 but the LWA program continued to be funded by the federal
      government until 2002. Trends in age standardised rates of acute and chronic
      alcohol-attributable deaths in the NT were examined before, during and after the
      combined implementation of the LWA program and Levy and before and during the
      full length of the LWA program. Auto-regressive integrated moving average (ARIMA)
      time series analyses included internal and external control series and
      adjustments for possible confounders. Separate estimates were made for Indigenous
      and non-Indigenous NT residents. FINDINGS: When combined, the Levy and the LWA
      program were associated with significant declines in acute alcohol-attributable
      deaths in the NT as well as Indigenous deaths between 1992 and 1997. A
      significant but delayed decline in chronic deaths was evident towards the end of
      the study period between 1998 and 2002. CONCLUSIONS: The combined impact of the
      LWA program Levy and the programs and services funded by the Levy reduced the
      burden of alcohol-attributable injury to the NT in the short term and may have
      contributed to a reduction in chronic illness in the longer term. The results of
      this study present a strong argument for the effectiveness of combining alcohol
      taxes with comprehensive programs and services designed to reduce the harm from
      alcohol, and underline the need to distinguish between the acute and chronic
      effects of alcohol in population level studies.

PMID- 16277625
TI  - Reasons for drinking less and their relationship to sustained remission from
      problem drinking.
AB  - AIMS: To compare representative general population and treated samples on their
      reasons for drinking less and whether particular reasons were related to
      sustained remission from problem drinking for either group. PARTICIPANTS AND
      DESIGN: A total of 659 problem drinking adults in a Northern California county
      identified through a probability survey in the general population (n = 239) and a
      survey of consecutive admissions to public and private alcohol and drug programs
      (n = 420), who reported drinking less at the one-year follow-up and provided
      reasons for reducing their drinking, were assessed 1-, 3-, and 5-years post
      baseline regarding their problem drinking status. MEASUREMENTS: Logistic
      regression models were used to predict sustained remission from problem drinking.
      RESULTS: While the treated sample endorsed a majority of reasons in significantly
      higher proportions than the general population sample, the same three reasons
      were significant for both groups in predicting sustained remission from problem
      drinking: hitting rock bottom, experiencing a traumatic event and undergoing a
      spiritual awakening. Interventions by medical personnel and family members were
      either non-significant predictors or significantly negatively related to
      sustained improvement for both general population and treated problem drinkers.
      CONCLUSIONS: General population and treatment samples have similar reasons for
      cutting down as they relate to sustained remission from problem drinking.

PMID- 16277626
TI  - Drinking in the Commonwealth of Independent States--evidence from eight
      countries.
AB  - AIMS: To describe the frequency of alcohol consumption and beverage preferences
      in eight countries of the Commonwealth of Independent States (CIS). DESIGN: Cross
      sectional. SETTING: Populations of Armenia, Belarus, Georgia, Kazakhstan,
      Kyrgyzstan, Republic of Moldova, Russian Federation and Ukraine. PARTICIPANTS:
      Representative samples of the adult population of each country (overall sample
      size 18,428; response rates: 71-88%). MEASUREMENTS: A standardised questionnaire
      was administered by trained interviewers to examine alcohol consumption frequency
      and usual intakes of beer, wine and strong spirits. FINDINGS: Between 11 and 34%
      of males and 26-71% of females reported never drinking alcohol. Abstention was
      lowest in the Russian Federation and Belarus, two traditional spirits-drinking
      countries. It was particularly high in Kyrgyzstan and Georgia, two countries with
      a relatively low frequency of alcohol consumption but large amounts consumed per
      occasion (particularly Georgia). On the contrary, Moldovan respondents drank
      frequently, but consumed smaller amounts per occasion. As expected, spirits were
      consumed in largest amounts in traditional spirits-drinking countries, as well as
      Armenia and wine in traditional wine-drinking countries. Beer consumption was
      relatively high in Russia, Belarus, Ukraine and Kazakhstan (males), particularly
      in young respondents. CONCLUSIONS: Although cross-country comparisons of alcohol
      intake should be interpreted cautiously, this study suggested that drinking
      patterns in the countries examined are not entirely typical of usual dry/wet
      drinking cultures, and confirms that the CIS is very diverse in terms of drinking
      patterns and beverage preferences. The study provides an important baseline for
      future comparisons as markets open to new products, as has been the case
      elsewhere in Europe.

PMID- 16277627
TI  - Cirrhosis mortality in Ontario: effects of alcohol consumption and Alcoholics
      Anonymous participation.
AB  - AIMS: We test the hypotheses that cirrhosis mortality rates are positively
      associated with per capita alcohol consumption and negatively associated with
      Alcoholics Anonymous (AA) membership rates. DESIGN: The impact of alcohol
      consumption levels and AA membership rates on cirrhosis mortality rates in
      Ontario from 1968 to 1989 were examined. Time-series analyses with ARIMA
      modelling were applied to male and female cirrhosis mortality rates in three age
      groups: 15-44, 45-64 and 65 + years. Missing AA membership data were interpolated
      using two methods: linear splines and cubic splines. FINDINGS: In general,
      cirrhosis mortality rates were positively associated with alcohol consumption and
      negatively associated with AA membership. For some age and gender combinations,
      these effects were not statistically significant. CONCLUSIONS: The limits of this
      study include restrictions in the length of series available and in the ability
      to infer causality. Despite these limitations, these findings are consistent with
      previous research demonstrating that per capita consumption is a strong
      determinant of cirrhosis mortality rates, and also that higher levels of AA
      membership can reduce cirrhosis mortality rates.

PMID- 16277628
TI  - The effects of self-administered alcohol-induced 'hangover' in a naturalistic
      setting on psychomotor and cognitive performance and subjective state.
AB  - AIMS: To examine in as naturalistic a setting as possible whether having an
      alcohol-induced 'hangover' impairs psychomotor and cognitive performance.
      PARTICIPANTS AND DESIGN: The sample consisted of 71 male and female social
      drinkers who were tested twice, once at baseline and once after exposure to the
      study condition. They were randomized into a control group who returned for
      testing on a prearranged date (n = 33), and a group who were instructed to make
      arrangements to return the day after a self-determined heavy drinking session (n
      = 38). Of the 'hangover' group, 13 participants still had a blood alcohol
      concentration of >1 mg/100 ml at the time of testing and these were analysed
      separately. All participants were students. MEASUREMENTS: Psychomotor performance
      was assessed by means of a battery of psychomotor tasks, rate of information
      processing was tested by the Speed and Capacity of Language Processing Test
      (SCOLP) and subjective state was assessed by questionnaire measures. FINDINGS:
      All participants in the 'hangover' group reported subjective and physical
      symptoms of hangover on the second testing session. Performance was significantly
      impaired on the hits-key components of the vigilance task, was less accurate on
      the primary and secondary reaction time tasks and showed greater dispersion in
      range of ability for participants in the 'acute and hangover' compared to
      'control'. Probe memory revealed no significant group effect. Ratings of
      subjective state revealed significant group differences for the variables
      'ability to drive', 'concentrate' and 'react quickly' as well as 'tiredness'.
      There were no group differences for performance on the SCOLP. CONCLUSION:
      Hangover had negative effects on self-reported subjective and physical state and
      subtle effects on performance.

PMID- 16277629
TI  - Harm reduction interventions, behaviours and associated health outcomes in
      France, 1996-2003.
AB  - AIMS: To track the effect of the French harm reduction programme targeted at
      intravenous drug users (IDUs) and associated health outcomes. MATERIAL: Since
      1996, we have collected monthly sales of sterile syringes and substitution
      treatments (buprenorphine high dosage and methadone) sold to IDUs in the 23 000
      pharmacies in France and collated these figures in a single data base (SIAMOIS).
      To this data base we have also added the number of syringes distributed through
      community associations, as well as methadone treatments prescribed in public drug
      dependence clinics. METHODS: For the period 1996-2003 we analysed syringe sales
      and prescribed substitution treatments as indicators of access to harm reduction
      services. We compared variations of these figures over time with trends in health
      outcome indicators [annual number of fatal overdoses, hepatitis C virus (HCV) and
      human immunodeficiency virus (HIV) prevalence among intravenous drug users], risk
      behaviour indicators (rate of syringe sharing or rate of syringe re-use) and
      legal indicators (heroin and cocaine use-related arrests). FINDINGS: The number
      of sterile syringes sold or distributed to IDUs increased from 1996 to 1999 (+
      21%) and then decreased dramatically from 1999 to 2003 (-40%). In 2003, we
      estimated that more than 100,000 drug users used substitution treatments. Between
      1996 and 2003, a decrease in syringe sharing and syringe re-use was observed, HIV
      prevalence among IDUs decreased from 40% to 20% and HCV prevalence remained high
      (60-70%). From 1996 to 2003, arrests due to heroin use declined (from 17 328 to
      4025) and deaths due to overdoses also decreased (from 465 to 89), whereas
      arrests for cocaine use increased from 1184 to 2511. CONCLUSION: Our results
      indicate that, since 1996 in France, IDUs have had greatly improved access to
      sterile syringes and substitution treatments. The decrease in syringe sharing and
      re-use practices and of HIV prevalence during the same time period indicates that
      the harm reduction policy implemented in France has had a positive impact.
      However, because of the persistent sharing and re-use of syringes and a remaining
      high HCV prevalence in IDUs, efforts to facilitate access to sterile syringes
      must continue, and targeting of at-risk groups must be improved. Behavioural
      surveys associated with HIV and HCV seroprevalence data are needed to further
      assess prevention of blood-borne infections among IDUs in France.

PMID- 16277630
TI  - Capturing crack cocaine use: estimating the prevalence of crack cocaine use in
      London using capture-recapture with covariates.
AB  - AIM: To estimate the prevalence of crack cocaine use in 12 London Boroughs (and
      London as a whole). SETTING: Twelve London Boroughs, 2000-01. METHODS: (1)
      Covariate capture-recapture techniques applied to three data sources of subjects
      reporting crack cocaine use: specialist drug treatment (2905), arrest referral
      (1188) and accident and emergency and community survey (531); and (2) ratio
      estimation multiplier, using an estimate of number of injecting drug users and
      proportion that use crack cocaine. FINDINGS: After matching, 4117 individuals
      aged 15-44 were identified. The best-fitting model estimated 16 855 unobserved
      crack cocaine users, giving an overall estimate of approximately 21 000 [95%
      confidence interval (CI) 13 000-43,000] and a prevalence of 1.5% (95% CI 1.0
      3.2%). Prevalence of crack cocaine use was 2.4% (95% CI 1.5-5.0%) among men and
      0.7% (95% CI 0.5-1.0%) among women, and similar by age groups 15-29 and 30-44
      years. Overall, approximately 11 900 (57%) of the estimated number of crack
      cocaine users were also opiate users. In London as a whole there may be 46,000
      (1.3%) crack cocaine users aged 15-44 years, with 28 000 (1.9%) in inner London
      four times higher than estimates from population surveys. Some corroboration was
      provided by the ratio-estimation method, which estimated 23 000 users in the 12
      Boroughs. CONCLUSIONS: Capture-recapture can be applied to crack cocaine and
      obtain better estimates than population surveys. The size of the crack cocaine
      using population in London is large, although currently the majority are also
      opiate users. Given that half of current users are under 30 the problems
      associated with crack cocaine use are likely to increase in the future.

PMID- 16277631
TI  - Correlates of regular cigarette smoking in a population-based sample of
      Australian twins.
AB  - AIMS: To investigate the role of measured risk factors and the influence of
      genetic and environmental factors on regular cigarette smoking. Design Members of
      monozygotic and dizygotic, including unlike-sex twin pairs (n = 6257) from a
      young adult cohort from the Australian Twin Registry. METHODS: Cox proportional
      hazards models were used to determine whether putative risk factors were
      significantly associated with regular cigarette smoking. Risk factors were
      classified into four tiers: tier 1 (parental history, including parental
      education, alcoholism and cigarette smoking), tier 2 (early home and family
      influences), tier 3 (early life events, e.g. trauma) and tier 4 (psychiatric
      symptoms/disorders with onset prior to 14 years), after controlling for gender,
      zygosity and their interactions. Genetic models were fitted to examine the
      heritability of smoking behavior before and after controlling for significant
      covariates from the four tiers. FINDINGS: Parental history of cigarette smoking
      and alcoholism, parental closeness and home environment, as well as incidence of
      childhood sexual abuse or other trauma, a history of early onset panic attacks
      and conduct problems were associated with regular cigarette smoking. Important
      age interactions were found, particularly for family background risk factors.
      Regular cigarette smoking was moderately heritable, even after accounting for
      significant covariates. CONCLUSIONS: Several measured risk factors are associated
      with regular smoking. While some of the genetic influences on regular smoking may
      be shared with these risk factors, a significant proportion of the genetic
      vulnerability to regular smoking is phenotype-specific.

PMID- 16277633
TI  - Smoking cessation intervention in parents of young children: a randomised
      controlled trial.
AB  - OBJECTIVE: To examine whether telephone counselling based on the stages of change
      component of Transtheoretical model of behaviour change together with educational
      materials could help non-motivated smoking parents of young children to cease.
      DESIGN: Randomised controlled trial. SETTING: Hong Kong Special Administrative
      Region, PR China. PARTICIPANTS: 952 smoker fathers and mothers of Chinese
      children aged 5 years. INTERVENTION: Participants were randomly allocated into
      two groups: the intervention group received printed self-help materials and three
      session telephone-based smoking cessation counselling delivered by trained
      counsellors; the control group received printed self-help materials only. A
      structured questionnaire was used for data collection at baseline and at 1, 3 and
      6 month follow up. MAIN OUTCOME MEASURES: The main outcome is 7 day point
      prevalence quit rate at 6 months (defined as not smoking during the 7 days
      preceding the 6 month follow up) determined by self reports. Other secondary
      outcomes were self reported 24 h point prevalence quit rate and self-reported
      continuous quit rate and bio-chemically validated quit rate at 6 months. RESULTS:
      A total of 952 smoker fathers and mothers were randomized to the intervention (n
      = 467) and control (n = 485) groups. Most were daily smokers (92.4%) and the mean
      number of cigarettes smoked per day was 14.5 (SD = 8.9). By using intention-to
      treat analysis, the 7 day point prevalence quit rate at 6 month follow up was
      significantly greater in the intervention group (15.3%; 68/444) than the control
      group (7.4%; 34/459) (P < 0.001). The absolute risk reduction was 7.9% (95%
      confidence interval: 3.78% to 12.01%). The number needed to treat to get one
      additional smoker to quit was 13 (95% CI: 8-26). The crude odds ratio of quitting
      was 2.3(95% CI: 1.5-3.5). The adjusted odds ratio was 2.1 (95% CI: 1.4-3.4)
      (adjusted for age, number of years smoked, and alcohol dependency). CONCLUSION:
      Proactive telephone counselling is an effective aid to promote smoking cessation
      among parents of young children.

PMID- 16277632
TI  - Comparative efficacy of rapid-release nicotine gum versus nicotine polacrilex gum
      in relieving smoking cue-provoked craving.
AB  - AIMS: Most relapse episodes occur when smokers are confronted with craving
      provoked by situational cues. Current nicotine gum can help relieve cue-provoked
      cravings, but faster effects may result in more rapid relief. We tested a
      prototype formulation of a new rapid-release nicotine gum (RRNG) that provides
      more rapid release and absorption of nicotine, for its ability to provide faster
      and better craving relief compared to current nicotine polacrilex gum (NPG).
      DESIGN: Random assignment to RRNG or NPG, used during a smoking cue provocation
      procedure. Participants and setting A total of 319 smokers were exposed to a
      smoking cue in the laboratory by being asked to light but not smoke a cigarette
      of their preferred brand. Subjects then chewed a piece of 2 mg RRNG (n = 159) or
      2 mg NPG (n = 160) according to randomized assignment. MEASUREMENTS: Craving
      assessments were completed at regular intervals before and after cue exposure
      (baseline, pre-cue, and 3, 6, 9, 12, 15, 18, 21, 25, 30 and 35 minutes after the
      cue). FINDINGS: Smokers chewing RRNG showed significantly lower craving than NPG
      subjects starting with the first assessment at 3 minutes (P < 0.025). Repeated
      measures ANOVA revealed a significant treatment x time interaction (P < 0.05)
      craving scores dropped more rapidly in RRNG subjects compared to NPG subjects.
      Survival analyses also indicated superiority of RRNG in achieving more rapid self
      reported meaningful relief (P < 0.05) and complete relief (P < 0.05) of craving.
      CONCLUSIONS: Rapid-release nicotine gum reduced cue-provoked craving more rapidly
      compared to NPG, and thus merits further study in cessation efficacy trials.

PMID- 16277634
TI  - Lessons from the ongoing UK injectable diamorphine shortage.

PMID- 16277635
TI  - General anaesthesia is patient-friendly in opioid antagonist detoxification
      treatment.

PMID- 16277637
TI  - Role for IL-4 nonproducing NKT cells in CC-chemokine ligand 2-induced Th2 cell
      generation.
AB  - NKT cells from C57Bl/6 mice are known to be the initial cellular source of IL-4
      that acts as a trigger for Th2 cell differentiation. CC-chemokine ligand 2 (CCL2)
      has been described as an initial stimulator of IL-4 production by these cells;
      however, IL-4 was not produced by NKT cells from BALB/c mice even when Th2 cell
      responses were established in these mice. In this study, we found a new pathway
      for CCL2-associated Th2 cell generation in BALB/c mice. Splenic T cells from
      BALB/c mice produced IL-4 in response to CCL2 stimulation. However, IL-4
      production was not seen in cultures of splenic T cells from CD1-/- mice (BALB/c
      origin), whereas, in the presence of CCL2, splenic T cells from CD1-/- mice
      produced IL-4 when NKT cells from wild-type mice were added. CCL2 induced IL-4 in
      cultures of NKT cells cocultured with naive T cells, but IL-4 was not produced by
      these cells cultured separately with CCL2. Interestingly, IL-4 was produced by
      naive T cells cocultured with NKT cells that were previously treated with CCL2
      (CCL2-NKT cells). In addition, IL-4 was produced by naive T cells supplemented
      with a culture supernatant of CCL2-NKT cells. These results indicate that,
      through the production of a soluble factor(s) other than IL-4, NKT cells play a
      role in the CCL2-associated generation of Th2 cells.

PMID- 16277638
TI  - Targeting the monocytic ubiquitin system with extracellular ubiquitin.
AB  - Recent findings suggest that extracellular ubiquitin has pleiotropic effects on
      host defence mechanisms, but its cellular mechanism of action is not yet
      understood. Using fluorescence and in vivo confocal microscopy, we observed
      uptake of N-terminal fluorescein-labelled ubiquitin into human PBMC and MonoMac 6
      cells. Immunoblotting experiments indicated that extracellular ubiquitin is then
      rapidly conjugated to a multitude of intracellular proteins. LPS and lipoteichoic
      acid significantly increased uptake and subsequent conjugation to intracellular
      proteins dose dependently. This mechanism showed saturation kinetics with a K(d)
      value for ubiquitin in the low nanomolar range (<10 nmol/L) and a B(max) value of
      0.14-0.27 micromol ubiquitin/mg protein. These results suggest that the monocytic
      ubiquitin system can be targeted with physiologically relevant concentrations of
      extracellular ubiquitin during inflammation. This concept could provide a simple
      explanation for a multitude of extracellular ubiquitin's actions and open up new
      strategies to influence ubiquitin-dependent intracellular processes.

PMID- 16277639
TI  - Perturbations in nuclear factor-kappaB or c-Jun N-terminal kinase pathways in
      pancreatic beta cells confer susceptibility to cytokine-induced cell death.
AB  - Pro-inflammatory cytokines have been implicated in the death of pancreatic beta
      cells leading to type 1 diabetes. NIT-1 cells are an insulinoma cell line derived
      from mice expressing the SV40 large T antigen. These cells are a useful tool in
      analysis of beta cell death. NIT-1 cells are highly susceptible to caspase
      dependent apoptosis induced by TNF-alpha alone. Primary islets are not
      susceptible to cell death induced by TNF-alpha alone; however, they are killed by
      TNF-alpha and IFN-gamma in a nitric oxide-dependent manner. We examined signal
      transduction in NIT-1 cells in response to cytokines to determine the mechanism
      for TNF-alpha-induced apoptosis. We found that NIT-1 cells are defective in the
      activation of nuclear factor-kappaB (NFkappaB) as a result of functionally
      deficient RelA activity, because overexpression of RelA protected NIT-1 cells
      from apoptosis. TNF-alpha also did not induce phosphorylation of c-Jun N-terminal
      kinase in NIT-1 cells. Together, these defects prevent expression of anti
      apoptotic genes in NIT-1 cells and make them susceptible to TNF-alpha. To
      determine whether similar defects in primary beta cells would induce the same
      effect, we examined TNF-alpha-induced apoptosis in islets isolated from mice
      deficient in NFkappaB p50. These islets were as susceptible as wild-type islets
      to TNF-alpha and IFN-gamma-induced cell death. In contrast to wild-type islets,
      cell death was not prevented by inhibition of nitric oxide in p50-deficient
      islets. Blocking NFkappaB has been proposed as a mechanism for protection of beta
      cells from cytokine-induced cell death in vivo. Our results suggest that this
      would make beta cells equally or more sensitive to cytokines.

PMID- 16277640
TI  - NKT cells are not critical for HSV-1 disease resolution.
AB  - NKT cells are a minor subset of T cells that have important roles in controlling
      immune responses in disease states including cancer, autoimmunity and pathogenic
      infections. In contrast to conventional T cells, NKT cells express an invariant
      TCR and respond to glycolipids presented by CD1d. In this study, we sought to
      investigate the role of NKT cells in regulating the response to infection with
      HSV-1, and the mechanism involved, in well-established mouse models. Previous
      studies of HSV-1 disease in mice have shown clear roles for CD4+ and CD8+ T
      cells. The role of NKT cells in the resolution of HSV-1 (KOS strain) infection
      was investigated through flank zosteriform or footpad infection in wild-type
      versus CD1d-deficient mice, by measurement of viral plaque-forming units at
      different sites after infection, lesion severity and HSV-1-specific T-cell
      responses. In contrast to a previous study using a more virulent strain of HSV-1
      (SC16 strain), no differences were observed in disease magnitude or resolution,
      and furthermore, the T-cell response to HSV-1 (KOS strain) was unaltered in the
      absence of NKT cells. In conclusion, this study shows that NKT cells do not play
      a general role in controlling the resolution or severity of HSV-1 infection.
      Instead, the resolution or severity of the infection may depend on the HSV-1
      strain under investigation.

PMID- 16277641
TI  - Refugee perceptions of the quality of healthcare: findings from a participatory
      assessment in Ngara, Tanzania.
AB  - This article describes the findings of a participatory assessment of Burundian
      and Rwandan refugees' perceptions of the quality of health services in camps in
      Ngara, Tanzania. Taking a beneficiary-centred approach, it examines a
      collaborative effort by several agencies to develop a generic field guide to
      analyse refugees' views of healthcare services. The objective was to gather
      information that would contribute to significant improvements in the care offered
      in the camps. Although the primary focus was on healthcare, several broader
      questions considered other general apprehensions that might influence the way
      refugees perceive their healthcare. Findings indicated that while refugees in
      Ngara were generally satisfied with the quality of healthcare provided and
      healthcare promotion activities, recognition of some key refugee concerns would
      assist healthcare providers in enhancing services. With increasing need for
      refugee community participation in evaluating humanitarian assistance, this
      assessment has relevance both in the context of Ngara and beyond.

PMID- 16277642
TI  - Setting up an early warning system for epidemic-prone diseases in Darfur: a
      participative approach.
AB  - In April-May 2004, the World Health Organization (WHO) implemented, with local
      authorities, United Nations (UN) agencies and non-governmental organisations
      (NGOs), an early warning system (EWS) in Darfur, West Sudan, for internally
      displaced persons (IDPs). The number of consultations and deaths per week for 12
      health events is recorded for two age groups (less than five years and five years
      and above). Thresholds are used to detect potential outbreaks. Ten weeks after
      the introduction of the system, NGOs were covering 54 camps, and 924,281 people
      (IDPs and the host population). Of these 54 camps, 41 (76%) were reporting
      regularly under the EWS. Between 22 May and 30 July, 179,795 consultations were
      reported: 18.7% for acute respiratory infections; 15% for malaria; 8.4% for
      bloody diarrhoea; and 1% for severe acute malnutrition. The EWS is useful for
      detecting outbreaks and monitoring the number of consultations required to
      trigger actions, but not for estimating mortality.

PMID- 16277643
TI  - Cracking the code: the genesis, use and future of the Code of Conduct.
AB  - This paper reflects on the genesis of the Code of Conduct for the International
      Red Cross and Red Crescent Movement and Non-Governmental Organizations (NGOs) in
      Disaster Relief, on the tenth anniversary of its adoption. The origins, usage and
      future of the code are examined with respect to three debates, current at the
      time of its inception, namely: the debate about the core content of
      humanitarianism; the debate about coherence and the consensual nature of the
      humanitarian community; and the debate about the need for, and the ability to
      demonstrate, accountability. The paper concludes that although the Code of
      Conduct was very much a product of its time, its content remains relevant today.
      However, its future application hinges on the capacity of those who purport to
      follow it to realise true accountability, and on proving that the code, written
      essentially for natural disasters, is relevant to contemporary complex
      emergencies.

PMID- 16277644
TI  - Making humanitarian relief networks more effective: operational coordination,
      trust and sense making.
AB  - Effective coordination of humanitarian assistance activities remains elusive.
      This paper briefly addresses some of the reasons for what is widely perceived as
      a coordination dilemma in humanitarian affairs and argues for a new
      conceptualisation of the issue. Rather than continue to request that more
      authority be vested in a single organisation to secure coordination through top
      down control, it contends that it may be timely to consider whether relief
      agencies involved in an emergency should be reconceived as social networks and
      efforts made to achieve changes in their organizational cultures that encourage
      operational coordination across institutional lines. Since such labours imply the
      need to trust, this article explores what forms of trust might be employed to
      promote improved coordination among relief institutions and how those
      relationships could themselves be conceptualised. Finally, while acknowledging
      that coordination is not costless, it suggests that its effective pursuit may be
      advantageous even in scenarios where aid organisations balk at cooperating to
      secure it.

PMID- 16277645
TI  - Dead letter or living document? Ten years of the Code of Conduct for disaster
      relief.
AB  - This paper examines the present value of the Code of Conduct for the
      International Red Cross and Red Crescent Movement and Non-Governmental
      Organizations (NGOs) in Disaster Relief, in view of discussions on neutrality and
      the Western bias of the humanitarian aid system, and assesses how it can retain
      its relevance in future. The Code of Conduct was launched just after the Rwanda
      genocide of April 1994. A decade later, the crises in Afghanistan and Iraq have
      sparked renewed interest in humanitarian principles and in whether the code can
      serve as an instrument to define humanitarianism and guide humanitarian decision
      making and coordination. More than 300 organisations have now subscribed to it.
      This paper is based on the findings of a survey of code signatories and the
      outcomes of a conference on the value and future of the code, held in The Hague,
      Netherlands, in September 2004 to mark its tenth anniversary.

PMID- 16277646
TI  - Evidence against disaster-induced migration: the 2004 tornado in north-central
      Bangladesh.
AB  - Migration is generally considered to be one of the primary responses to a natural
      disaster. The existing literature widely acknowledges the fact that disaster
      victims migrate from affected areas. This paper, though, provides empirical
      evidence of the non-occurrence of out-migration in the aftermath of the 14 April
      2004 tornado in Bangladesh. Data collected from 291 respondents from eight
      tornado-affected villages suggest that no one from these locations migrated to
      other areas. The constant flow of disaster aid and its proper distribution by the
      government and non-governmental organisations (NGOs) were the main reasons why
      victims did not leave. This study contributes to the disaster literature by
      providing three important findings: disasters do not always create out-migration;
      emergency aid can compensate in monetary terms for damage caused by disasters;
      and some of the arguments made in the literature against the provision of
      emergency relief for disaster victims are not always valid for all countries.

PMID- 16277647
TI  - Morphed facial expressions elicited a N400 ERP effect: a domain-specific semantic
      module?
AB  - Previous studies have revealed that decoding of facial expressions is a specific
      component of face comprehension and that semantic information might be processed
      separately from the basic stage of face perception. In order to explore event
      related potentials (ERPs) related to recognition of facial expressions and the
      effect of the semantic content of the stimulus, we analyzed 20 normal subjects.
      Faces with three prototypical emotional expressions (fear, happiness, and
      sadness) and with three morphed expressions were presented in random order. The
      neutral stimuli represented the control condition. Whereas ERP profiles were
      similar with respect to an early negative ERP (N170), differences in peak
      amplitude were observed later between incongruous (morphed) expressions and
      congruous (prototypical) ones. In fact, the results demonstrated that the
      emotional morphed faces elicited a negative peak at about 360 ms, mainly
      distributed over the posterior site. The electrophysiological activity observed
      may represent a specific cognitive process underlying decoding of facial
      expressions in case of semantic anomaly detection. The evidence is in favor of
      the similarity of this negative deflection with the N400 ERP effect elicited in
      linguistic tasks. A domain-specific semantic module is proposed to explain these
      results.

PMID- 16277648
TI  - Is emotional content obtained from parafoveal words during reading? An eye
      movement analysis.
AB  - An eye-movement-contingent display change technique was employed to study whether
      adult readers extract semantic information from parafoveal words during reading.
      Three types of parafoveal preview conditions were contrasted: an emotional word,
      a neutral word, and an identical word condition. To have a maximally effective
      parafoveal manipulation, high-arousal emotional words (sex- and threat-related
      and curse words) were used as parafoveal previews. Readers' eye fixation patterns
      around the target word revealed no evidence for parafoveal semantic processing.
      Furthermore, the pupil size showed no signs for an emotional response triggered
      by an emotional word previewed parafoveally. These results are consistent with
      the view that, as a rule, only the fixated word is processed to a semantic level
      during reading.

PMID- 16277649
TI  - Communicative skills in relation to gender, birth order, childcare and
      socioeconomic status in 18-month-old children.
AB  - Variation in communicative skills, defined as gestures, vocabulary comprehension
      and vocabulary production, was examined as a function of gender, birth order,
      childcare and socioeconomic status (SES) in 1,019 18-month-old children. The
      children were recruited at their regular check-up at a number of randomly
      selected Child Health Care centers in a Swedish county. The participation rate
      was 88%. The children were assessed by their mothers using a short version of the
      Swedish Early Communicative Development Inventories. The results demonstrate
      significant effects of gender and birth order on vocabulary comprehension and
      vocabulary production. Girls scored higher than boys and first-born children
      scored higher than later-born children. Type of childcare (family care, care at
      home and day-care centers) interacted with gender and birth order on vocabulary
      production and indicated that family care is not as advantageous as care at home
      or at day-care centers. SES had no effect on children's communicative skills at
      this age.

PMID- 16277650
TI  - Basic information processing of neurotics and stables: an experimental ERP
      approach to personality and distractibility.
AB  - The aim of the study was to investigate the effects of level of neuroticism on
      electrophysiological event-related potentials (ERPs) to different kinds of
      stimuli. The neuroticism items from the NEO-PI-R were administered to 168 female,
      right-handed undergraduates between 19 and 29 years of age. 20 highly neurotic
      and 22 highly stable persons underwent an ERP task that was designed to be a
      combination of an auditory P3a and a visual P3b oddball task. No significant
      differences in the P3a and P3b were detected. It is concluded that highly
      neurotic and highly stable persons do not differ in fast neurocognitive
      processing of neutral stimuli, and that cognitive differences between the groups
      may be located at another level in the sequence of information processing stages.

PMID- 16277651
TI  - Trauma narratives and emotional processing.
AB  - The present study examined the relations between indicators of emotional
      processing (e.g. trauma narratives), posttraumatic stress symptoms, and
      psychological distress in two military samples (N = 120) exposed to significant
      training accidents. Trauma narratives were collected at 2-3 weeks, while outcome
      measures (e.g. IES-15, PTSS-10, and GHQ-30) were collected at 2-3 weeks, and 4
      months after the accidents. Emotional processing was indexed by the content of
      positive and negative emotional expressions in the trauma narratives. The results
      showed that positive emotional expressions were associated with lower levels of
      psychological distress, whereas negative emotional expressions were linked to
      trauma specific symptoms and psychological distress at 2-3 weeks. Negative
      emotional expressions explained between 6-8% of the variance in trauma specific
      symptoms at 2-3 weeks, and 11% of the variance in psychological distress symptoms
      at 4 months after the traumatic event.

PMID- 16277652
TI  - Ideological commitment and posttraumatic stress in former Tamil child soldiers.
AB  - This study focuses on the impact of present ideological commitment on
      posttraumatic stress symptoms in former child soldiers living in exile. Eighteen
      men and two women (aged 25-37), who had joined different Tamil armed groups in
      Sri Lanka between the ages of 13 and 17 years, participated. The Impact of Event
      Scale was used to measure posttraumatic symptoms. Qualitative methods were used
      to investigate the participants' ideological commitment. Participants reported
      being exposed to many potentially traumatizing events, and had high scores on the
      Impact of Event Scale. Twenty-five percent of the sample showed strong
      ideological commitment to the "cause". Ideological commitment at the present
      seemed to predict better mental health when exposure was less intense and
      overwhelming. Time had a negative impact on ideological commitment.

PMID- 16277653
TI  - A psychometric assessment of a Swedish translation of Spreitzer's empowerment
      scale.
AB  - The psychometric properties of a Swedish translation of Spreitzer's (1995a)
      empowerment scale were assessed. Three parallel assessments were made of data
      from 1,107 female registered nurses, 758 female assistant nurses, and 107 male
      registered and assistant nurses. The analyses indicated that the psychometric
      properties of the scale can be considered satisfactory. Suggestions are made
      regarding future research in the fields of psychometrics and work- and health
      psychology.

PMID- 16277654
TI  - Complement receptor 1 polymorphisms associated with resistance to severe malaria
      in Kenya.
AB  - BACKGROUND: It has been hypothesized that the African alleles Sl2 and McCb of the
      Swain-Langley (Sl) and McCoy (McC) blood group antigens of the complement
      receptor 1 (CR1) may confer a survival advantage in the setting of Plasmodium
      falciparum malaria, but this has not been demonstrated. METHODS: To test this
      hypothesis, children in western Kenya with severe malaria-associated anaemia or
      cerebral malaria were matched to symptomatic uncomplicated malaria controls by
      age and gender. Swain-Langley and McCoy blood group alleles were determined by
      restriction fragment length polymorphism and conditional logistic regression was
      carried out. RESULTS: No significant association was found between the African
      alleles and severe malaria-associated anaemia. However, children with Sl2/2
      genotype were less likely to have cerebral malaria (OR = 0.17, 95% CI 0.04 to
      0.72, P = 0.02) than children with Sl1/1. In particular, individuals with Sl2/2
      McC(a/b) genotype were less likely to have cerebral malaria (OR = 0.18, 95% CI
      0.04 to 0.77, P = 0.02) than individuals with Sl1/1 McC(a/a). CONCLUSION: These
      results support the hypothesis that the Sl2 allele and, possibly, the McCb allele
      evolved in the context of malaria transmission and that in certain combinations
      probably confer a survival advantage on these populations.

PMID- 16277656
TI  - Coronary artery to left ventricle fistula.
AB  - BACKGROUND: Coronary cameral fistulas are an uncommon entity, the etiology of
      which may be congenital or traumatic. They involve abnormal termination of a
      coronary artery, usually the right coronary, into a cardiac chamber, usually the
      right ventricle. CASE PRESENTATION: We describe a case of female patient with
      severe aortic stenosis and interventricular septal hypertrophy that underwent
      bioprosthetic aortic valve replacement with concomitant septal myectomy. On
      subsequent follow-up an abnormal flow traversing the septum into the left
      ventricle was identified and Doppler interrogation demonstrated a continuous
      flow, with a predominantly diastolic component, consistent with coronary arterial
      flow. CONCLUSION: The literature on coronary cameral fistulas is reviewed and the
      etiology of the diagnostic findings discussed. In our patient, a coronary artery
      to left ventricle fistula was the most likely explanation secondary to trauma to
      the septal perforator artery during myectomy. Since the patient was asymptomatic
      at the time of diagnosis no intervention was recommended and has done well on
      follow-up.

PMID- 16277655
TI  - Lymphoscintigraphy and triangulated body marking for morbidity reduction during
      sentinel node biopsy in breast cancer.
AB  - Current trends in patient care include the desire for minimizing invasiveness of
      procedures and interventions. This aim is reflected in the increasing utilization
      of sentinel lymph node biopsy, which results in a lower level of morbidity in
      breast cancer staging, in comparison to extensive conventional axillary
      dissection. Optimized lymphoscintigraphy with triangulated body marking is a
      clinical option that can further reduce morbidity, more than when a hand held
      gamma probe alone is utilized. Unfortunately it is often either overlooked or not
      fully understood, and thus not utilized. This results in the unnecessary loss of
      an opportunity to further reduce morbidity. Optimized lymphoscintigraphy and
      triangulated body marking provides a detailed 3 dimensional map of the number and
      location of the sentinel nodes, available before the first incision is made. The
      number, location, relevance based on time/sequence of appearance of the nodes,
      all can influence 1) where the incision is made, 2) how extensive the dissection
      is, and 3) how many nodes are removed. In addition, complex patterns can arise
      from injections. These include prominent lymphatic channels, pseudo-sentinel
      nodes, echelon and reverse echelon nodes and even contamination, which are much
      more difficult to access with the probe only. With the detailed information
      provided by optimized lymphoscintigraphy and triangulated body marking, the
      surgeon can approach the axilla in a more enlightened fashion, in contrast to
      when the less informed probe only method is used. This allows for better
      planning, resulting in the best cosmetic effect and less trauma to the tissues,
      further reducing morbidity while maintaining adequate sampling of the sentinel
      node(s).

PMID- 16277657
TI  - SSH adequacy to preimplantation mammalian development: scarce specific
      transcripts cloning despite irregular normalisation.
AB  - BACKGROUND: SSH has emerged as a widely used technology to identify genes that
      are differentially regulated between two biological situations. Because it
      includes a normalisation step, it is used for preference to clone low abundance
      differentially expressed transcripts. It does not require previous sequence
      knowledge and may start from PCR amplified cDNAs. It is thus particularly well
      suited to biological situations where specific genes are expressed and tiny
      amounts of RNA are available. This is the case during early mammalian embryo
      development. In this field, few differentially expressed genes have been
      characterized from SSH libraries, but an overall assessment of the quality of SSH
      libraries is still required. Because we are interested in the more systematic
      establishment of SSH libraries from early embryos, we have developed a simple and
      reliable strategy based on reporter transcript follow-up to check SSH library
      quality and repeatability when starting with small amounts of RNA. RESULTS: Four
      independent subtracted libraries were constructed. They aimed to analyze key
      events in the preimplantation development of rabbit and bovine embryos. The
      performance of the SSH procedure was assessed through the large-scale screening
      of thousands of clones from each library for exogenous reporter transcripts
      mimicking either tester specific or tester/driver common transcripts. Our results
      show that abundant transcripts escape normalisation which is only efficient for
      rare and moderately abundant transcripts. Sequencing 1600 clones from one of the
      libraries confirmed and extended our results to endogenous transcripts and
      demonstrated that some very abundant transcripts common to tester and driver
      escaped subtraction. Nonetheless, the four libraries were greatly enriched in
      clones encoding for very rare (0.0005% of mRNAs) tester-specific transcripts.
      CONCLUSION: The close agreement between our hybridization and sequencing results
      shows that the addition and follow-up of exogenous reporter transcripts provides
      an easy and reliable means to check SSH performance. Despite some cases of
      irregular normalisation and subtraction failure, we have shown that SSH
      repeatedly enriches the libraries in very rare, tester-specific transcripts, and
      can thus be considered as a powerful tool to investigate situations where small
      amounts of biological material are available, such as during early mammalian
      development.

PMID- 16277658
TI  - Role of retinoic acid receptors in squamous-cell carcinoma in human esophagus.
AB  - BACKGROUND: Worldwide, cancer in the esophagus ranks among the 10 most common
      cancers. Alterations of retinoic acid receptors (e.g. RARalpha, beta, gamma, and
      RXRalpha, beta, gamma) expression is considered to play an important role in
      development of squamous-cell carcinoma (SCC), which is the most common esophageal
      cancer. Alcohol consumption and smoking, which can alter retinoic acid receptor
      levels, have been identified as key risk factors in the development of carcinoma
      in the aero-digestive tract. Therefore, the aim of the present study was to
      evaluate protein levels of retinoic acid receptors (i.e. RARalpha, beta, gamma,
      and RXRbeta) in esophageal SCC and surrounding normal tissue of patients with
      untreated SCC and controls. METHODS: All study participants completed a
      questionnaire concerning smoking and alcohol drinking habits as well as
      anthropometrical parameters. Protein levels of RARalpha, beta, gamma, and RXRbeta
      were determined by Western Blot in normal esophageal tissue and tissue obtained
      from SCC of 21 patients with newly diagnosed esophageal SCC and normal esophageal
      tissue of 10 controls. RESULTS: Protein levels of RARgamma were significantly
      lower by approximately 68% in SCC compared to normal surrounding tissue in
      patients with SCC that smoked and/or consumed elevated amounts of alcohol.
      Furthermore, RARalpha protein levels were significantly lower (approximately-
      45%) in SCC in comparison to normal esophageal mucosa in patients with elevated
      alcohol intake. When comparing protein levels of retinoic acid receptors between
      normal tissue of patients with SCC and controls, RARgamma protein levels were
      found to be significantly higher (approximately 2.7-fold) in normal esophageal
      tissue of SCC patients than in esophageal tissue obtained from controls. No
      differences were found for RARalpha, beta, and RXRbeta protein levels between
      normal esophageal tissue of patients and that of controls. CONCLUSION: In
      conclusion, results of the present study suggest that alterations of retinoic
      acid receptors protein may contribute in the development of SCC in esophagus and
      that in some patients life style (e.g. smoking and alcohol consumption) may be a
      critical component in the alteration of retinoic acid receptor levels in
      esophagus.

PMID- 16277659
TI  - The Beijing genotype and drug resistant tuberculosis in the Aral Sea region of
      Central Asia.
AB  - BACKGROUND: After the collapse of the Soviet Union, dramatically increasing rates
      of tuberculosis and multidrug-resistant tuberculosis (MDR-TB) have been reported
      from several countries. This development has been mainly attributed to the
      widespread breakdown of TB control systems and declining socio-economic status.
      However, recent studies have raised concern that the Beijing genotype of
      Mycobacterium tuberculosis might be contributing to the epidemic through its
      widespread presence and potentially enhanced ability to acquire resistance.
      METHODS: A total of 397 M. tuberculosis strains from a cross sectional survey
      performed in the Aral Sea region in Uzbekistan and Turkmenistan have been
      analysed by drug susceptibility testing, IS6110 fingerprinting, and
      spoligotyping. RESULTS: Fifteen isolates showed mixed banding patterns indicating
      simultaneous infection with 2 strains. Among the remaining 382 strains, 152 (40%)
      were grouped in 42 clusters with identical fingerprint and spoligotype patterns.
      Overall, 50% of all isolates were Beijing genotype, with 55% of these strains
      appearing in clusters compared to 25% of non-Beijing strains. The percentage of
      Beijing strains increased with increasing drug resistance among both new and
      previously treated patients; 38% of fully-susceptible isolates were Beijing
      genotype, while 75% of MDR-TB strains were of the Beijing type. CONCLUSION: The
      Beijing genotype is a major cause of tuberculosis in this region, it is strongly
      associated with drug resistance, independent of previous tuberculosis treatment
      and may be strongly contributing to the transmission of MDR-TB. Further
      investigation around the consequences of Beijing genotype infection for both
      tuberculosis transmission and outcomes of standard short course chemotherapy are
      urgently needed.

PMID- 16277661
TI  - A national, geographic database of CDC-funded HIV prevention services:
      development challenges and potential applications.
AB  - BACKGROUND: From 2000-2002, the Centers for Disease Control and Prevention (CDC)
      funded a study that was designed to improve the information available to program
      planners about the geographic distribution of CDC-funded HIV prevention services
      provided by community-based organizations (CBOs). Program managers at CDC
      recognized the potential of a geographic information system (GIS) to organize and
      analyze information about HIV prevention services and they made GIS a critical
      component of the study design. The primary objective of this study was to
      construct a national, geographically-referenced database of HIV prevention
      services provided by CDC-funded CBOs. We designed a survey instrument to collect
      information about the geographic service areas where CBOs provided HIV prevention
      services, then collected data from CBOs that received CDC funding for these
      services during fiscal year 2000. We developed a GIS database to link
      questionnaire responses with GIS map layers in a manner that would incorporate
      overlapping geographies, risk populations and prevention services. We collected
      geographic service area data in two formats: 1) geopolitical boundaries and 2)
      geographic distance. RESULTS: The survey response rate was 70.3%, i.e. 1,020 of
      1,450 community-based organizations responded. The number of HIV prevention
      programs administered by each CBO ranged from 1 to 23. The survey provided
      information about 3,028 prevention programs, including descriptions of
      intervention types, risk populations, race and ethnicity, CBO location and
      geographic service area. We incorporated this information into a large GIS
      database, the HIV Prevention Services Database. The use of geopolitical
      boundaries provided more accurate results than geographic distance. The use of a
      reference map with the questionnaire improved completeness, accuracy and
      precision of service area data. CONCLUSION: The survey instrument design and
      database development procedures that we used for this study successfully met our
      objective. The development of the HIV Prevention Services Database for CDC is an
      important step toward the implementation of a spatial decision support system.
      Due to the costs involved in a nationwide survey such as this, we recommend that
      future data collection efforts use Web-based survey methodologies that
      incorporate interactive maps.

PMID- 16277660
TI  - Unusual linkage patterns of ligands and their cognate receptors indicate a novel
      reason for non-random gene order in the human genome.
AB  - BACKGROUND: Prior to the sequencing of the human genome it was typically assumed
      that, tandem duplication aside, gene order is for the most part random. Numerous
      observers, however, highlighted instances in which a ligand was linked to one of
      its cognate receptors, with some authors suggesting that this may be a general
      and/or functionally important pattern, possibly associated with recombination
      modification between epistatically interacting loci. Here we ask whether ligands
      are more closely linked to their receptors than expected by chance. RESULTS: We
      find no evidence that ligands are linked to their receptors more closely than
      expected by chance. However, in the human genome there are approximately twice as
      many co-occurrences of ligand and receptor on the same human chromosome as
      expected by chance. Although a weak effect, the latter might be consistent with a
      past history of block duplication. Successful duplication of some ligands, we
      hypothesise, is more likely if the cognate receptor is duplicated at the same
      time, so ensuring appropriate titres of the two products. CONCLUSION: While there
      is an excess of ligands and their receptors on the same human chromosome, this
      cannot be accounted for by classical models of non-random gene order, as the
      linkage of ligands/receptors is no closer than expected by chance. Alternative
      hypotheses for non-random gene order are hence worth considering.

PMID- 16277662
TI  - Evaluating change in health-related quality of life in adult rhinitis:
      responsiveness of the Rhinosinusitis Disability Index.
AB  - BACKGROUND: The Rhinosinusitis Disability Index (RSDI) is a validated measure of
      health-related quality of life (HRQL) in rhinitis. Responsiveness of the RSDI to
      changes in health status over time has not been described. METHODS: We studied
      adults with a self-reported physician diagnosis of rhinitis identified through a
      national telephone survey. HRQL was assessed at baseline and at 24 months using
      the RSDI. Symptom severity, physical health status (SF-12 PCS), psychological
      mood (CES-D), and perceived control of symptoms were also assessed at the time of
      each interview. In addition, we ascertained specific health outcomes attributed
      to rhinitis, including days of restricted activity, job effectiveness, number of
      physician visits, and medication costs. RESULTS: Of 109 subjects interviewed at
      baseline, 69 (63%) were re-interviewed 24 months later. RSDI scores improved by =
      0.5 standardized response mean in 13 (19%) subjects and worsened in 17 (25%).
      Change in the RSDI over time correlated with changes in symptom severity (r =
      0.38, p = 0.001), physical health (r = -0.39, p = 0.001), mood (r = 0.37, p =
      0.002) and perceived control of symptoms (r = -0.37, p = 0.01). In multivariate
      analyses adjusted for baseline health status, improvement in RSDI was associated
      with less restricted activity (p = 0.01), increased job effectiveness (p = 0.03),
      and decreased medication costs (p = 0.05), but was not associated with change in
      the number of physician visits from baseline (p = 0.45). CONCLUSION: The RSDI is
      responsive to changes in health status and predicts rhinitis-specific health
      outcomes.

PMID- 16277663
TI  - Evidence-based ethics? On evidence-based practice and the "empirical turn" from
      normative bioethics.
AB  - BACKGROUND: The increase in empirical methods of research in bioethics over the
      last two decades is typically perceived as a welcomed broadening of the
      discipline, with increased integration of social and life scientists into the
      field and ethics consultants into the clinical setting, however it also
      represents a loss of confidence in the typical normative and analytic methods of
      bioethics. DISCUSSION: The recent incipiency of "Evidence-Based Ethics" attests
      to this phenomenon and should be rejected as a solution to the current
      ambivalence toward the normative resolution of moral problems in a pluralistic
      society. While "evidence-based" is typically read in medicine and other life and
      social sciences as the empirically-adequate standard of reasonable practice and a
      means for increasing certainty, I propose that the evidence-based movement in
      fact gains consensus by displacing normative discourse with aggregate or
      statistically-derived empirical evidence as the "bottom line". Therefore, along
      with wavering on the fact/value distinction, evidence-based ethics threatens
      bioethics' normative mandate. The appeal of the evidence-based approach is that
      it offers a means of negotiating the demands of moral pluralism. Rather than
      appealing to explicit values that are likely not shared by all, "the evidence" is
      proposed to adjudicate between competing claims. Quantified measures are notably
      more "neutral" and democratic than liberal markers like "species normal
      functioning". Yet the positivist notion that claims stand or fall in light of the
      evidence is untenable; furthermore, the legacy of positivism entails the quieting
      of empirically non-verifiable (or at least non-falsifiable) considerations like
      moral claims and judgments. As a result, evidence-based ethics proposes to
      operate with the implicit normativity that accompanies the production and
      presentation of all biomedical and scientific facts unchecked. SUMMARY: The
      "empirical turn" in bioethics signals a need for reconsideration of the methods
      used for moral evaluation and resolution, however the options should not include
      obscuring normative content by seemingly neutral technical measure.

PMID- 16277665
TI  - Prevalence of pre- and postpartum depression in Jamaican women.
AB  - BACKGROUND: Maternal depression during pregnancy has been studied less than
      depression in postpartum period. The aims of this study were to find out the
      prevalence of prepartum and postpartum depression and the risk factors associated
      in a cohort of Afro-Jamaican pregnant women in Jamaica. METHODS: The Zung self
      rating depression scale instrument was administered to 73 healthy pregnant women
      at 28 weeks gestation and at 6 weeks postpartum for quantitative measurement of
      depression. Blood samples were collected at 8, 28, 35 weeks gestation and at day
      1 and 6 weeks postpartum to study the thyroid status. RESULTS: Study demonstrated
      depression prevalence rates of 56% and 34% during prepartum and postpartum
      period, respectively. 94% women suffering depression in both periods were single.
      There were significant variations in both FT3 and TT4 concentrations which
      increased from week 8 to week 28 prepartum (p < 0.05) and then declined at the
      35th week (p < 0.05 compared with week 28) and 1 day post delivery study (p <
      0.05 compared with week 35). The mean values for TSH increased significantly from
      week 8 through week 35. The mean values at 1 day postpartum and 6 week postpartum
      were not significantly different from the 35 week values. For FT3, TT4 and TSH
      there were no significant between group differences in concentrations. The major
      determinants of postpartum depression were moderate and severe prepartum
      depression and change in TT4 hormone concentrations. CONCLUSION: High prevalence
      of depression was found during pre- and postpartum periods. Single mothers,
      prepartum depression and changes in TT4 were factors found to be significantly
      associated with postpartum depression.

PMID- 16277664
TI  - The zebrafish progranulin gene family and antisense transcripts.
AB  - BACKGROUND: Progranulin is an epithelial tissue growth factor (also known as
      proepithelin, acrogranin and PC-cell-derived growth factor) that has been
      implicated in development, wound healing and in the progression of many cancers.
      The single mammalian progranulin gene encodes a glycoprotein precursor consisting
      of seven and one half tandemly repeated non-identical copies of the cystine-rich
      granulin motif. A genome-wide duplication event hypothesized to have occurred at
      the base of the teleost radiation predicts that mammalian progranulin may be
      represented by two co-orthologues in zebrafish. RESULTS: The cDNAs encoding two
      zebrafish granulin precursors, progranulins-A and -B, were characterized and
      found to contain 10 and 9 copies of the granulin motif respectively. The cDNAs
      and genes encoding the two forms of granulin, progranulins-1 and -2, were also
      cloned and sequenced. Both latter peptides were found to be encoded by precursors
      with a simplified architecture consisting of one and one half copies of the
      granulin motif. A cDNA encoding a chimeric progranulin which likely arises
      through the mechanism of trans-splicing between grn1 and grn2 was also
      characterized. A non-coding RNA gene with antisense complementarity to both grn1
      and grn2 was identified which may have functional implications with respect to
      gene dosage, as well as in restricting the formation of the chimeric form of
      progranulin. Chromosomal localization of the four progranulin (grn) genes reveals
      syntenic conservation for grna only, suggesting that it is the true orthologue of
      mammalian grn. RT-PCR and whole-mount in situ hybridization analysis of zebrafish
      grns during development reveals that combined expression of grna and grnb, but
      not grn1 and grn2, recapitulate many of the expression patterns observed for the
      murine counterpart. This includes maternal deposition, widespread central nervous
      system distribution and specific localization within the epithelial compartments
      of various organs. CONCLUSION: In support of the duplication-degeneration
      complementation model of duplicate gene retention, partitioning of expression
      between grna and grnb was observed in the intermediate cell mass and yolk
      syncytial layer, respectively. Taken together these expression patterns suggest
      that the function of an ancestral grn gene has been devolved upon four paralogues
      in zebrafish.

PMID- 16277666
TI  - A descriptive study of older adults with persistent pain: use and perceived
      effectiveness of pain management strategies [ISRCTN11899548].
AB  - BACKGROUND: Persistent pain is a common, often debilitating, problem in older
      adults; however, few studies have focused on the experiences of older adults in
      managing their pain. The objective of this study was to describe the use and
      perceived effectiveness of pain management strategies in a sample of older adults
      and to explore the associations of these variables with demographic and
      psychosocial characteristics. METHODS: Adults >or= 65 years old and living in
      retirement facilities who reported persistent pain (N = 235, mean age = 82 years,
      84% female, 94% white) completed measures of demographics, pain, depression, self
      efficacy for managing pain, and a Pain Management Strategies Survey. Participants
      identified current and previous-year use of 42 pain management strategies and
      rated helpfulness of each on a 5-point scale. RESULTS: Acetaminophen, regular
      exercise, prayer, and heat and cold were the most frequently used pain management
      strategies (61%, 58%, 53%, and 48%, respectively). Strategies used by >25% of the
      sample that were rated moderately or more helpful (i.e., >2 on a 0 to 4 scale)
      were prayer [mean (SD) = 2.9 (0.9)], opioids [2.6 (0.8)], regular exercise [2.5
      (1.0)], heat/cold [2.5 (1.0)], nonsteroidal anti-inflammatory drugs [2.4 (1.0)],
      and acetaminophen [2.3 (1.0)]. Young-old (65-74 years) study participants
      reported use of more strategies than did old-old (85+ years) participants (p =
      .03). Perceived helpfulness of strategy use was significantly associated with
      pain intensity (r = -.14, p < .0001), self-efficacy (r = .28, p < .0001), and
      depression (r = -.20, p = .003). CONCLUSION: On average, older adults view the
      strategies they use for persistent pain as only moderately helpful. The
      associations between perceived helpfulness and self-efficacy and depression
      suggest avenues of pain management that are focused less on specific treatments
      and more on how persons with persistent pain think about their pain.

PMID- 16277667
TI  - Molecular and cytological features of the mouse B-cell lymphoma line iMycEmu-1.
AB  - BACKGROUND: Myc-induced lymphoblastic B-cell lymphoma (LBL) in iMycEmu mice may
      provide a model system for the study of the mechanism by which human MYC
      facilitates the initiation and progression of B cell and plasma cell neoplasms in
      human beings. We have recently shown that gene-targeted iMycEmu mice that carry a
      His6-tagged mouse Myc cDNA, MycHis, just 5' of the immunoglobulin heavy-chain
      enhancer, Emu, are prone to B cell and plasma cell tumors. The predominant tumor
      (approximately 50%) that arose in the iMycEmu mice on the mixed genetic
      background of segregating C57BL/6 and 129/SvJ alleles was LBL. The purpose of
      this study was to establish and characterize a cell line, designated iMycEmu-1,
      for the in-depth evaluation of LBL in vitro. METHODS: The morphological features
      and the surface marker expression profile of the iMycEmu-1 cells were evaluated
      using cytological methods and FACS, respectively. The cytogenetic make-up of the
      iMycEmu-1 cells was assessed by spectral karyotyping (SKY). The expression of the
      inserted MycHis gene was determined using RT-PCR and qPCR. Clonotypic
      immunoglobulin gene arrangements were detected by Southern blotting. The global
      gene expression program of the iMycEmu-1 cells and the expression of 768
      "pathway" genes were determined with the help of the Mouse Lymphochip(c) and
      Superarray(c) cDNA micro- and macroarrays, respectively. Array results were
      verified, in part, by RT-PCR and qPCR. RESULTS: Consistent with their derivation
      from LBL, the iMycEmu-1 cells were found to be neoplastic IgMhighIgDlow
      lymphoblasts that expressed typical B-cell surface markers including CD40, CD54
      (ICAM-1), CD80 (B7-1) and CD86 (B7-2). The iMycEmu-1 cells harbored a reciprocal
      T(9;11) and three non-reciprocal chromosomal translocations, over-expressed
      MycHis at the expense of normal Myc, and exhibited gene expression changes on
      Mouse Lymphochip microarrays that were consistent with MycHis-driven B-cell
      neoplasia. Upon comparison to normal B cells using eight different Superarray
      cDNA macroarrays, the iMycEmu-1 cells showed the highest number of changes on the
      NFkappaB array. CONCLUSION: The iMycEmu-1 cells may provide a uniquely useful
      model system to study the growth and survival requirements of Myc-driven mouse
      LBL in vitro.

PMID- 16277668
TI  - Expression of ADAM15 in rheumatoid synovium: up-regulation by vascular
      endothelial growth factor and possible implications for angiogenesis.
AB  - ADAMs (a disintegrin and metalloproteinases) comprise a new gene family of
      metalloproteinases, and may play roles in cell-cell interaction, cell migration,
      signal transduction, shedding of membrane-anchored proteins and degradation of
      extracellular matrix. We screened the mRNA expression of 10 different ADAMs with
      a putative metalloproteinase motif in synovial tissues from patients with
      rheumatoid arthritis (RA) or osteoarthritis (OA). Reverse transcription PCR and
      real-time quantitative PCR analyses indicated that among the ADAMs, ADAM15 mRNA
      was more frequently expressed in the RA samples and its expression level was
      significantly 3.8-fold higher in RA than in OA (p < 0.01). In situ hybridization,
      immunohistochemistry and immunoblotting demonstrated that ADAM15 is expressed in
      active and precursor forms in the synovial lining cells, endothelial cells of
      blood vessels and macrophage-like cells in the sublining layer of RA synovium.
      There was a direct correlation between ADAM15 mRNA expression levels and vascular
      density in the synovial tissues (r = 0.907, p < 0.001; n = 20). ADAM15 was
      constitutively expressed in RA synovial fibroblasts and human umbilical vein
      endothelial cells (HUVECs), and the expression level was increased in HUVECs by
      treatment with vascular endothelial growth factor (VEGF)165. On the other hand,
      ADAM15 expression in RA synovial fibroblasts was enhanced with VEGF165 only if
      vascular endothelial growth factor receptor (VEGFR)-2 expression was induced by
      treatment with tumor necrosis factor-alpha, and the expression was blocked with
      SU1498, a specific inhibitor of VEGFR-2. These data demonstrate that ADAM15 is
      overexpressed in RA synovium and its expression is up-regulated by the action of
      VEGF165 through VEGFR-2, and suggest the possibility that ADAM15 is involved in
      angiogenesis in RA synovium.

PMID- 16277670
TI  - A functional variant of Fcgamma receptor IIIA is associated with rheumatoid
      arthritis in individuals who are positive for anti-glucose-6-phosphate isomerase
      antibodies.
AB  - Anti-glucose-6-phosphate isomerase (GPI) antibodies are known to be arthritogenic
      autoantibodies in K/BxN mice, although some groups have reported that few healthy
      humans retain these antibodies. The expression of Fcgamma receptors (FcgammaRs)
      is genetically regulated and has strong implications for the development of
      experimental arthritis. The interaction between immune complexes and FcgammaRs
      might therefore be involved in the pathogenesis of some arthritic conditions. To
      explore the relationship between functional polymorphisms in FcgammaRs (FCGR3A
      158V/F and FCGR2A-131H/R) and arthritis in individuals positive for anti-GPI
      antibodies, we evaluated these individuals with respect to FCGR genotype.
      Genotyping for FCGR3A-158V/F and FCGR2A-131H/R was performed by PCR amplification
      of the polymorphic site, followed by site specific restriction digestion using
      the genome of 187 Japanese patients with rheumatoid arthritis (including 23 who
      were anti-GPI antibody positive) and 158 Japanese healthy individuals (including
      nine who were anti-GPI antibody positive). We report here on the association of
      FCGR3A-158V/F functional polymorphism with anti-GPI antibody positive status.
      Eight out of nine healthy individuals who were positive for anti-GPI antibodies
      possessed the homozygous, low affinity genotype FCGR3A-158F (odds ratio = 0.09,
      95% confidence interval 0.01-0.89; P = 0.0199), and probably were 'protected'
      from arthritogenic antibodies. Moreover, among those who were homozygous for the
      high affinity genotype FCGR3A-158V/V, there were clear differences in anti-human
      and anti-rabbit GPI titres between patients with rheumatoid arthritis and healthy
      subjects (P = 0.0027 and P = 0.0015, respectively). Our findings provide a
      molecular model of the genetic regulation of autoantibody-induced arthritis by
      allele-specific affinity of the FcgammaRs.

PMID- 16277669
TI  - Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis
      and inflammation-associated cachexia in rats.
AB  - Tetrathiomolybdate (TM), a drug developed for Wilson's disease, produces an anti
      angiogenic and anti-inflammatory effect by reducing systemic copper levels. TM
      therapy has proved effective in inhibiting the growth of tumors in animal tumor
      models and in cancer patients. We have hypothesized that TM may be used for the
      therapy of rheumatoid arthritis and have examined the efficacy of TM on adjuvant
      induced arthritis in the rat, which is a model of acute inflammatory arthritis
      and inflammatory cachexia. TM delayed the onset of and suppressed the severity of
      clinical arthritis on both paw volume and the arthritis score. Histological
      examination demonstrated that TM significantly reduces the synovial hyperplasia
      and inflammatory cell invasion in joint tissues. Interestingly, TM can inhibit
      the expression of vascular endothelial growth factor in serum synovial tissues,
      especially in endothelial cells and macrophages. Moreover, the extent of pannus
      formation, which leads to bone destruction, is correlated with the content of
      vascular endothelial growth factor in the serum. There was no mortality in TM
      treated rat abnormalities. TM also suppressed inflammatory cachexia. We suggest
      that copper deficiency induced by TM is a potent approach both to inhibit the
      progression of rheumatoid arthritis with minimal adverse effects and to improve
      the well-being of rheumatoid arthritis patients.

PMID- 16277671
TI  - The contact-mediated response of peripheral-blood monocytes to preactivated T
      cells is suppressed by serum factors in rheumatoid arthritis.
AB  - Stimulation of monocytes/macrophages after cell contact with preactivated T cells
      has been suggested to contribute to the excessive TNF-alpha production in
      rheumatoid arthritis (RA). In this study, T cell-contact-dependent TNF-alpha
      production by peripheral-blood monocytes in vitro was investigated and found to
      be significantly lower in treated and untreated patients with RA than in healthy
      controls. This suppression was not due to a general deficiency of monocytes to
      respond, because responses to lipopolysaccharide were comparable in patients and
      controls. In agreement with the pivotal role of TNF-alpha in RA, T cell-dependent
      induction of TNF-alpha in synovial macrophages was fivefold to tenfold higher
      than in peripheral-blood monocytes from either patients or controls. The
      decreased response of peripheral-blood monocytes from patients with RA was found
      to be mediated by inhibitory serum factors, because the addition of patient sera
      to monocytes from healthy controls suppressed TNF-alpha response in the co
      culture assay. Preincubation of monocytes from healthy controls with RA serum was
      sufficient to suppress the subsequent TNF-alpha response in T cell co-cultures,
      indicating that inhibitory factors do indeed bind to monocyte surfaces, which
      might represent a regulatory counter-action of the immune system to the long
      standing and consuming autoimmune process in RA. There are some indications that
      apolipoprotein A-1 might be part of this regulatory system.

PMID- 16277672
TI  - Rheumatoid arthritis seropositive for the rheumatoid factor is linked to the
      protein tyrosine phosphatase nonreceptor 22-620W allele.
AB  - The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes for
      lymphoid tyrosine phosphatase LYP, involved in the negative regulation of early T
      cell activation. An association has recently been reported between the PTPN22
      620W functional allele and rheumatoid factor-positive (RF+) rheumatoid arthritis
      (RA), among other autoimmune diseases. Expected linkage proof for consistency
      cannot be definitely produced by an affected sib-pair (ASP) analysis. Our aim was
      therefore to search for linkage evidence with the transmission disequilibrium
      test. DNA from the French Caucasian population was available for two samples of
      100 families with one RA patient and both parents, and for 88 RA index cases from
      RA ASP families. Genotyping was carried out by PCR-restriction fragment length
      polymorphism. The analysis was performed using the transmission disequilibrium
      test, genotype relative risk and ASP-based analysis. The transmission
      disequilibrium test of the PTPN22-620W allele revealed linkage and association
      for RF+ RA (61% of transmission, P = 0.037). The genotype relative risk showed
      the risk allele in 34% of RF+ RA patients and in 24% of controls derived from
      nontransmitted parental chromosomes (P = 0.047, odds ratio = 1.69, 95% confidence
      interval = 1.03-2.78). The ASP investigation showed no enriched risk allele in RA
      multiplex families, resulting in a lack of power of ASP analysis, explaining the
      published negative results. This study is the first to show linkage of PTPN22 to
      RF+ RA, consistent with PTPN22 as a new RA gene.

PMID- 16277674
TI  - Absence of autoantibodies against correctly folded recombinant fibrillin-1
      protein in systemic sclerosis patients.
AB  - Autoantibodies against short recombinant fragments of fibrillin-1 produced in
      bacterial expression systems have been found in tight-skin mouse, systemic
      sclerosis, mixed connective tissue disease, and primary pulmonary hypertension
      syndrome. In patients with scleroderma, the frequency of anti-fibrillin-1
      antibodies was 42% in Caucasians. Until now it has been unclear whether this
      immune response has a primary function in disease pathogenesis or is a secondary
      phenomenon. In the present study we analyzed the frequency of autoantibodies
      against two overlapping recombinant polypeptides spanning the N-terminal and C
      terminal halves of human fibrillin-1, which were produced in human embryonic
      kidney (HEK-293) cells. Correct three-dimensional structures of the recombinant
      fibrillin-1 polypeptides were shown by electron microscopy and immunoreactivity
      with antibodies. Screening of fibrillin-1 antibodies was performed in 41 sera
      from systemic sclerosis patients and in 44 healthy controls with a Caucasian
      background. Microtiter plates were coated with the recombinant polypeptides of
      fibrillin-1 and incubated with 1:100 diluted sera. Positive binding was defined
      as being more than 2 SD above the mean of the control group. ELISAs showed that
      none of the sera of patients with systemic sclerosis contained autoantibodies
      against the N-terminal or C-terminal recombinant fibrillin-1 polypeptide. The
      data show the absence of autoantibodies against recombinant fibrillin-1 protein
      in Caucasian systemic sclerosis patients. Because the correct three-dimensional
      folding of the recombinant proteins has been substantiated by several independent
      methods, we conclude that autoantibodies against correctly folded fibrillin are
      not a primary phenomenon in the pathogenesis of systemic sclerosis.

PMID- 16277673
TI  - Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen
      induced arthritis.
AB  - CXCL12 (stromal cell-derived factor 1) is a unique biological ligand for the
      chemokine receptor CXCR4. We previously reported that treatment with a specific
      CXCR4 antagonist, AMD3100, exerts a beneficial effect on the development of
      collagen-induced arthritis (CIA) in the highly susceptible IFN-gamma receptor
      deficient (IFN-gammaR KO) mouse. We concluded that CXCL12 plays a central role in
      the pathogenesis of CIA in IFN-gammaR KO mice by promoting delayed type
      hypersensitivity against the auto-antigen and by interfering with chemotaxis of
      CXCR4+ cells to the inflamed joints. Here, we investigated whether AMD3100 can
      likewise inhibit CIA in wild-type mice and analysed the underlying mechanism.
      Parenteral treatment with the drug at the time of onset of arthritis reduced
      disease incidence and modestly inhibited severity in affected mice. This
      beneficial effect was associated with reduced serum concentrations of IL-6.
      AMD3100 did not affect anti-collagen type II antibodies and, in contrast with its
      action in IFN-gammaR KO mice, did not inhibit the delayed type hypersensitivity
      response against collagen type II, suggesting that the beneficial effect cannot
      be explained by inhibition of humoral or cellular autoimmune responses. AMD3100
      inhibited the in vitro chemotactic effect of CXCL12 on splenocytes, as well as in
      vivo leukocyte infiltration in CXCL12-containing subcutaneous air pouches. We
      also demonstrate that, in addition to its effect on cell infiltration, CXCL12
      potentiates receptor activator of NF-kappaB ligand-induced osteoclast
      differentiation from splenocytes and increases the calcium phosphate-resorbing
      capacity of these osteoclasts, both processes being potently counteracted by
      AMD3100. Our observations indicate that CXCL12 acts as a pro-inflammatory factor
      in the pathogenesis of autoimmune arthritis by attracting inflammatory cells to
      joints and by stimulating the differentiation and activation of osteoclasts.

PMID- 16277675
TI  - Polymorphism in the tumour necrosis factor receptor II gene is associated with
      circulating levels of soluble tumour necrosis factor receptors in rheumatoid
      arthritis.
AB  - Levels of soluble tumour necrosis factor receptors (sTNFRs) are elevated in the
      circulation of patients with rheumatoid arthritis (RA). Although these receptors
      can act as natural inhibitors of tumour necrosis factor-alpha, levels of sTNFRs
      in RA appear to be insufficient to prevent tumour necrosis factor-alpha induced
      inflammation. The factors that regulate circulating levels of sTNFRs are unclear,
      but polymorphisms in the tumour necrosis factor receptor genes may play a role.
      We investigated the relationship between polymorphisms in the tumour necrosis
      factor receptor I (TNF-RI) and II (TNF-RII) genes and levels of sTNFRs in two
      groups of Caucasian RA patients: one with early (disease duration < or = 2 years;
      n = 103) and one with established disease (disease duration > or = 5 years; n =
      151). PCR restriction fragment length polymorphism analysis was used to genotype
      patients for the A36G polymorphism in the TNF-RI gene and the T676G polymorphism
      in TNF-RII. Levels of sTNFRs were measured using ELISA. We also isolated T cells
      from peripheral blood of 58 patients with established RA with known TNF-R
      genotypes, and release of sTNFRs into the culture medium was measured in cells
      incubated with or without phytohaemagglutinin. Serum levels of the two sTNFRs
      (sTNF-RI and sTNF-RII) were positively correlated in both populations, and the
      level of each sTNFR was significantly higher in the patients with established
      disease (P < 0.0001). Multiple regression analyses corrected for age, sex and
      disease duration revealed a significant trend toward decreasing sTNF-RI and sTNF
      RII levels across the TNF-RII genotypes (TT > TG > GG) of patients with
      established disease (P for trend = 0.01 and P for trend = 0.03, respectively). A
      similar nonsignificant trend was seen for early disease. No relationship with the
      TNF-RI A36G polymorphism was observed. sTNFRs released by isolated T cells
      exhibited a similar trend toward decreasing levels according to TNF-RII genotype,
      although only the association with levels of sTNF-RII was significant. Strong
      correlations were found between levels of circulating sTNFRs and levels released
      by T cells in vitro. Our data indicate that the T676G polymorphism in TNF-RII is
      associated with levels of sTNFRs released from peripheral blood T cells, and with
      circulating levels of sTNFR in patients with RA.

PMID- 16277676
TI  - Elimination of rheumatoid synovium in situ using a Fas ligand 'gene scalpel'.
AB  - Surgical synovectomy to remove the inflammatory synovium can temporarily
      ameliorate rheumatoid inflammation and delay the progress of joint destruction.
      An efficient medically induced programmed cell death (apoptosis) in the
      rheumatoid synovium might play a role similar to synovectomy but without surgical
      tissue damage. Gene transfer of Fas ligand (FasL) has increased the frequency of
      apoptotic cells in mouse and rabbit arthritic synovium. In this study, we
      investigated whether repeated FasL gene transfer could remove human inflammatory
      synovial tissue in situ and function as a molecular synovectomy. Briefly,
      specimens of human synovium from joint replacement surgeries and synovectomies of
      rheumatoid arthritis (RA) patients were grafted subcutaneously into male C.B-17
      severe combined immunodeficiency (SCID) mice. Injections of a recombinant FasL
      adenovirus (Ad-FasL) into the grafted synovial tissue at the dosage of 10(11)
      particles per mouse were performed every two weeks. Three days after the fifth
      virus injection, the mice were euthanized by CO2 inhalation and the human
      synovial tissues were collected, weighed and further examined. Compared to the
      control adenovirus-LacZ (Ad-LacZ) and phosphate buffered saline (PBS) injected RA
      synovium, the Ad-FasL injected RA synovium was dramatically reduced in size and
      weight (P < 0.005). The number of both synoviocytes & mononuclear cells was
      significantly reduced. Interestingly, an approximate 15-fold increased frequency
      of apoptotic cells was observed in RA synovium three days after Ad-FasL
      injection, compared with control tissues. In summary, our in vivo investigation
      of gene transfer to human synovium in SCID mice suggests that repeated intra
      articular gene transfer of an apoptosis inducer, such as FasL, may function as a
      'gene scalpel' for molecular synovectomy to arrest inflammatory synovium at an
      early stage of RA.

PMID- 16277677
TI  - Raloxifene reduces urokinase-type plasminogen activator-dependent proliferation
      of synoviocytes from patients with rheumatoid arthritis.
AB  - Extracellular fibrinolysis, controlled by the membrane-bound fibrinolytic system,
      is involved in cartilage damage and rheumatoid arthritis (RA) synovitis. Estrogen
      status and metabolism seem to be impaired in RA, and synoviocytes show receptors
      for estrogens. Our aims in this study were to evaluate in healthy and RA
      synoviocytes the effects of Raloxifene (RAL), a selective estrogen receptor
      modulator (SERM), on: proliferation; the components of the fibrinolytic system;
      and chemoinvasion. The effects of RAL were studied in vitro on synoviocytes from
      four RA patients and four controls. Proliferation was evaluated as cell number
      increase, and synoviocytes were treated with 0.5 microM and 1 microM RAL with and
      without urokinase-plasminogen activator (u-PA) and anti-u-PA/anti-u-PA receptor
      (u-PAR) antibodies. Fibrinolytic system components (u-PA, u-PAR and plasminogen
      activator inhibitor (PAI)-1) were assayed by ELISA with cells treated with 0.5
      microM and 1 microM RAL for 48 h. u-PA activity was evaluated by zymography and a
      direct fibrinolytic assay. U-PAR/cell and its saturation were studied by
      radioiodination of u-PA and a u-PA binding assay. Chemoinvasion was measured
      using the Boyden chamber invasion assay. u-PA induced proliferation of RA
      synoviocytes was blocked by RAL (p < 0.05) and antagonized by antibodies alone.
      The inhibitory effect of RAL was not additive with u-PA/u-PAR antagonism. RA
      synoviocytes treated with RAL showed, compared to basal, higher levels of PAI-1
      (10.75 +/- 0.26 versus 5.5 +/- 0.1 microg/10(6) cells, respectively; p < 0.01),
      lower levels of u-PA (1.04 +/- 0.05 versus 3.1 +/- 0.4 ng/10(6) cells,
      respectively; p < 0.001), and lower levels of u-PAR (11.28 +/- 0.22 versus 23.6
      +/- 0.1 ng/10(6) cells, respectively; p < 0.001). RAL also significantly
      inhibited u-PA-induced migration. Similar effects were also shown, at least
      partially, in controls. RAL exerts anti-proliferative and anti-invasive effects
      on synoviocytes, mainly modulating u-PAR and, to a lesser extent, u-PA and PAI-1
      levels, and inhibiting cell migration and proliferation.

PMID- 16277679
TI  - Aerobic exercise and its impact on musculoskeletal pain in older adults: a 14
      year prospective, longitudinal study.
AB  - We studied the long term impact of running and other aerobic exercise on
      musculoskeletal pain in a cohort of healthy aging male and female seniors who had
      been followed for 14 years. We conducted a prospective, longitudinal study in 866
      Runners' Association members (n = 492) and community controls (n = 374). Subjects
      were also categorized as Ever-Runners (n = 565) and Never-Runners (n = 301) to
      include runners who had stopped running. Pain was the primary outcome measure and
      was assessed in annual surveys on a double-anchored visual analogue scale (0 to
      100; 0 = no pain). Baseline differences between Runners' Association members and
      community controls and between Ever-Runners versus Never-Runners were compared
      using chi-square and t-tests. Statistical adjustments for age, body mass index
      (BMI), gender, health behaviors, history of arthritis and comorbid conditions
      were performed using generalized estimating equations. Runner's Association
      members were younger (62 versus 65 years, p < 0.05), had a lower BMI (22.9 versus
      24.2, p < 0.05), and less arthritis (35% versus 41%, p > 0.05) than community
      controls. Runners' Association members averaged far more exercise minutes per
      week (314 versus 123, p < 0.05) and miles run per week (26 versus 2, p < 0.05)
      and tended to report more fractures (53% versus 47%, p > 0.05) than controls.
      Ever-Runners were younger (62 versus 66 years, p < 0.05), had lower BMI (23.0
      versus 24.3, p < 0.05), and less arthritis (35% versus 43%, p < 0.05) than Never
      Runners. Ever-Runners averaged more exercise minutes per week (291 versus 120, p
      < 0.05) and miles run per week (23 versus 1, p < 0.05) and reported a few more
      fractures (52% versus 48%, p > 0.05) than Never-Runners. Exercise was associated
      with significantly lower pain scores over time in the Runners' Association group
      after adjusting for gender, baseline BMI, and study attrition (p < 0.01). Similar
      differences were observed for Ever-Runners versus Never-Runners. Consistent
      exercise patterns over the long term in physically active seniors are associated
      with about 25% less musculoskeletal pain than reported by more sedentary
      controls, either by calendar year or by cumulative area-under-the-curve pain over
      average ages of 62 to 76 years.

PMID- 16277678
TI  - Inflammation causes tissue-specific depletion of vitamin B6.
AB  - Previously we observed strong and consistent associations between vitamin B6
      status and several indicators of inflammation in patients with rheumatoid
      arthritis. Clinical indicators, including the disability score, the length of
      morning stiffness, and the degree of pain, and biochemical markers, including the
      erythrocyte sedimentation rate and C-reactive protein levels, were found to be
      inversely correlated with circulating vitamin B6 levels. Such strong associations
      imply that impaired vitamin B6 status in these patients results from
      inflammation. In the present study we examined whether inflammation directly
      alters vitamin B6 tissue contents and its excretion in vivo. A cross-sectional
      case-controlled human clinical trial was performed in parallel with experiments
      in an animal model of inflammation. Plasma and erythrocyte and pyridoxal 5'
      phosphate concentrations, urinary 4-pyridoxic acid excretion, and the activity
      coefficient of erythrocyte aspartate aminotransferase were compared between
      patients and healthy subjects. Adjuvant arthritis was induced in rats for
      investigating hepatic and muscle contents as well as the urinary excretion of
      vitamin B6 during acute and chronic inflammation. Patients with rheumatoid
      arthritis had low plasma pyridoxal 5'-phosphate compared with healthy control
      subjects, but normal erythrocyte pyridoxal 5'-phosphate and urinary 4-pyridoxic
      acid excretion. Adjuvant arthritis in rats did not affect 4-pyridoxic acid
      excretion or muscle storage of pyridoxal 5'-phosphate, but it resulted in
      significantly lower pyridoxal 5'-phosphate levels in circulation and in liver
      during inflammation. Inflammation induced a tissue-specific depletion of vitamin
      B6. The low plasma pyridoxal 5'-phosphate levels seen in inflammation are
      unlikely to be due to insufficient intake or excessive vitamin B6 excretion.
      Possible causes of decreased levels of vitamin B6 are discussed.

PMID- 16277681
TI  - Open label phase II trial of single, ascending doses of MRA in Caucasian children
      with severe systemic juvenile idiopathic arthritis: proof of principle of the
      efficacy of IL-6 receptor blockade in this type of arthritis and demonstration of
      prolonged clinical improvement.
AB  - Eighteen Caucasian (white, Middle East and Asian) children diagnosed by
      paediatric rheumatologists in the UK and France as having systemic juvenile
      idiopathic arthritis (sJIA) were enrolled in this open label, single dose trial.
      All patients had evidence of continued symptoms and disease activity for at least
      three months while receiving >0.2 mg/kg/day of prednisolone, or its equivalent,
      prior to recruitment. Twelve patients also received methotrexate (< or =20
      mg/m2/week). The patients were divided into three groups receiving 2, 4 or 8
      mg/kg of MRA (tocilizumab) by intravenous infusion. No evidence of dose-limiting
      toxicity was observed and there were no dose-limiting safety issues. MRA appeared
      to be dramatically effective, with clinical and laboratory responses observed by
      48 h post infusion, and these improvements continued well after serum MRA was
      undetectable. Eleven patients achieved the JIA definition of improvement (at
      least 3 of 6 core set criteria with a 30% improvement and no more than one
      worsened by 30%) and eight achieved > or =50% improvement. There were no
      observable differences with age. Clinical improvement in these children was
      observed for up to eight weeks, supporting the hypothesis that IL-6 is a key
      cytokine in the upregulation of genes crucial in the inflammation processes of
      sJIA, and the possibility of sequestration of MRA in the extra-vascular
      compartment needs to be considered.

PMID- 16277680
TI  - Tumour necrosis factor-alpha stimulates dehydroepiandrosterone metabolism in
      human fibroblast-like synoviocytes: a role for nuclear factor-kappaB and
      activator protein-1 in the regulation of expression of cytochrome p450 enzyme 7b.
AB  - Glucocorticoids have successfully been used in the treatment of rheumatoid
      arthritis. Data suggest that 7alpha-hydroxy-dehydroepiandrosterone (7alpha-OH
      DHEA), an immunostimulating metabolite of dehydroepiandrosterone, can block
      glucocorticoid-induced immune suppression. Formation of 7alpha-OH-DHEA is
      catalyzed by activity of cytochrome p450 enzyme 7b (Cyp7b). Recently, we reported
      that tumour necrosis factor (TNF)-alpha, IL-1alpha, IL-1beta and IL-17 enhance
      Cyp7b mRNA expression and induce a concomitant increase in the formation of
      7alpha-OH-DHEA by fibroblast-like synoviocytes (FLS) from rheumatoid arthritis
      patients. The aim of this study was to elucidate which signal transduction
      pathway is involved in the TNF-alpha-mediated induction of Cyp7b activity in FLS.
      We studied the effects of inhibitors of different signal transduction pathways on
      Cyp7b activity in FLS by measuring Cyp7b mRNA expression using reverse
      transcription PCR and by measuring the formation of 7alpha-OH-DHEA. We applied
      SN50, an inhibitor of nuclear translocation of transcription factors (i.e.
      activator protein-1 [AP-1] and nuclear factor-kappaB [NF-kappaB]); PSI, a
      proteasome inhibitor that prevents IkappaB degradation and thereby NF-kappaB
      release; SP600125, a c-Jun N-terminal kinase (JNK) inhibitor; and the mitogen
      activated protein kinase inhibitors PD98059 (extracellular signal-regulated
      kinase) and SB203580 (p38). Cyp7b is constitutively expressed in RA FLS and can
      be activated in response to TNF-alpha. SN50 and PSI prevented the TNF-alpha
      induced increase in Cyp7b activity, whereas the mitogen-activated protein kinase
      inhibitors PD98059 and SB203580 had no effect. In addition, inhibition of Cyp7b
      mRNA expression and activity was observed with SN50, PSI and SP600125, suggesting
      that NF-kappaB and AP-1 induce Cyp7b transcription. These findings suggest that
      NF-kappaB and AP-1 are involved in the TNF-alpha-enhanced formation of the
      dehydroepiandrosterone metabolite 7alpha-OH-DHEA. Our results are in accordance
      with presence of AP-1 and NF-kappaB binding sites in the Cyp7b promoter.

PMID- 16277682
TI  - Segregation of a M404V mutation of the p62/sequestosome 1 (p62/SQSTM1) gene with
      polyostotic Paget's disease of bone in an Italian family.
AB  - Mutations of the p62/Sequestosome 1 gene (p62/SQSTM1) account for both sporadic
      and familial forms of Paget's disease of bone (PDB). We originally described a
      methionine-->valine substitution at codon 404 (M404V) of exon 8, in the ubiquitin
      protein-binding domain of p62/SQSTM1 gene in an Italian PDB patient. The
      collection of data from the patient's pedigree provided evidence for a familial
      form of PDB. Extension of the genetic analysis to other relatives in this family
      demonstrated segregation of the M404V mutation with the polyostotic PDB phenotype
      and provided the identification of six asymptomatic gene carriers. DNA for
      mutational analysis of the exon 8 coding sequence was obtained from 22 subjects,
      4 PDB patients and 18 clinically unaffected members. Of the five clinically
      ascertained affected members of the family, four possessed the M404V mutation and
      exhibited the polyostotic form of PDB, except one patient with a single X-ray
      assessed skeletal localization and one with a polyostotic disease who had died
      several years before the DNA analysis. By both reconstitution and mutational
      analysis of the pedigree, six unaffected subjects were shown to bear the M404V
      mutation, representing potential asymptomatic gene carriers whose circulating
      levels of alkaline phosphatase were recently assessed as still within the normal
      range. Taken together, these results support a genotype-phenotype correlation
      between the M404V mutation in the p62/SQSTM1 gene and a polyostotic form of PDB
      in this family. The high penetrance of the PDB trait in this family together with
      the study of the asymptomatic gene carriers will allow us to confirm the proposed
      genotype-phenotype correlation and to evaluate the potential use of mutational
      analysis of the p62/SQSTM1 gene in the early detection of relatives at risk for
      PDB.

PMID- 16277683
TI  - Association between occupational exposure to mineral oil and rheumatoid
      arthritis: results from the Swedish EIRA case-control study.
AB  - The aim of the present study was to investigate the association between exposure
      to mineral oil and the risk of developing rheumatoid arthritis (RA), and in
      addition to perform a separate analysis on the major subphenotypes for the
      disease; namely, rheumatoid factor (RF)-positive RA, RF-negative RA,
      anticitrulline-positive RA and anticitrulline-negative RA, respectively. A
      population-based case-control study of incident cases of RA was performed among
      the population aged 18-70 years in a defined area of Sweden during May 1996
      December 2003. A case was defined as an individual from the study base who for
      the first time received a diagnosis of RA according to the American College of
      Rheumatology criteria of 1987. Controls were randomly selected from the study
      base with consideration taken for age, gender and residential area. Cases (n =
      1,419) and controls (n = 1,674) answered an extensive questionnaire regarding
      lifestyle factors and occupational exposures, including different types of
      mineral oils. Sera from cases and controls were investigated for RF and
      anticitrulline antibodies. Among men, exposure to any mineral oil was associated
      with a 30% increased relative risk of developing RA (relative risk = 1.3, 95%
      confidence interval = 1.0-1.7). When cases were subdivided into RF-positive RA
      and RF-negative RA, an increased risk was only observed for RF-positive RA
      (relative risk = 1.4, 95% confidence interval 1.0-2.0). When RA cases were
      subdivided according to the presence of anticitrulline antibodies, an increased
      risk associated with exposure to any mineral oil was observed only for
      anticitrulline-positive RA (relative risk = 1.6, 95% confidence interval = 1.1
      2.2). Analysis of the interaction between oil exposure and the presence of HLA-DR
      shared epitope genes regarding the incidence of RA indicated that the increased
      risk associated with exposure to mineral oil was not related to the presence of
      shared epitope genotypes. In conclusion, our study shows that exposure to mineral
      oil is associated with an increased risk to develop RF-positive RA and
      anticitrulline-positive RA, respectively. The findings are of particular interest
      since the same mineral oils can induce polyarthritis in rats.

PMID- 16277684
TI  - Transcriptional profiles discriminate bone marrow-derived and synovium-derived
      mesenchymal stem cells.
AB  - Previous studies have reported that mesenchymal stem cells (MSC) may be isolated
      from the synovial membrane by the same protocol as that used for synovial
      fibroblast cultivation, suggesting that MSC correspond to a subset of the
      adherent cell population, as MSC from the stromal compartment of the bone marrow
      (BM). The aims of the present study were, first, to better characterize the MSC
      derived from the synovial membrane and, second, to compare systematically, in
      parallel, the MSC-containing cell populations isolated from BM and those derived
      from the synovium, using quantitative assays. Fluorescent-activated cell sorting
      analysis revealed that both populations were negative for CD14, CD34 and CD45
      expression and that both displayed equal levels of CD44, CD73, CD90 and CD105, a
      phenotype currently known to be characteristic of BM-MSC. Comparable with BM-MSC,
      such MSC-like cells isolated from the synovial membrane were shown for the first
      time to suppress the T-cell response in a mixed lymphocyte reaction, and to
      express the enzyme indoleamine 2,3-dioxygenase activity to the same extent as BM
      MSC, which is a possible mediator of this suppressive activity. Using
      quantitative RT-PCR these data show that MSC-like cells from the synovium and BM
      may be induced to chondrogenic differentiation and, to a lesser extent, to
      osteogenic differentiation, but the osteogenic capacities of the synovium-derived
      MSC were significantly reduced based on the expression of the markers tested
      (collagen type II and aggrecan or alkaline phosphatase and osteocalcin,
      respectively). Transcription profiles, determined with the Atlas Human
      Cytokine/Receptor Array, revealed discrimination between the MSC-like cells from
      the synovial membrane and the BM-MSC by 46 of 268 genes. In particular, activin A
      was shown to be one major upregulated factor, highly secreted by BM-MSC. Whether
      this reflects a different cellular phenotype, a different amount of MSC in the
      synovium-derived population compared with BM-MSC adherent cell populations or the
      impact of a different microenvironment remains to be determined. In conclusion,
      although the BM-derived and synovium-derived MSC shared similar phenotypic and
      functional properties, both their differentiation capacities and transcriptional
      profiles permit one to discriminate the cell populations according to their
      tissue origin.

PMID- 16277685
TI  - Induction of a B-cell-dependent chronic arthritis with glucose-6-phosphate
      isomerase.
AB  - Antibodies specific for glucose-6-phosphate isomerase (G6PI) from T-cell receptor
      transgenic K/BxN mice are known to induce arthritis in mice, and immunization of
      DBA/1 mice with G6PI led to acute arthritis without permanent deformation of
      their joints. Because rheumatoid arthritis is a chronic disease, we set out to
      identify the capacity of G6PI to induce chronic arthritis in mice. Immunization
      with recombinant human G6PI induced a chronically active arthritis in mice with a
      C3H genomic background, whereas the DBA/1 background allowed only acute arthritis
      and the C57BL/10 background permitted no or very mild arthritis. The disease was
      associated with the major histocompatibility region sharing an allelic
      association similar to that of collagen-induced arthritis (i.e. q > p > r). All
      strains developed a strong antibody response to G6PI that correlated only in the
      C3H.NB strain with arthritis severity. Similarly, a weak response to type II
      collagen in a few mice was observed, which was associated with arthritis in
      C3H.NB mice. Mice on the C3H background also developed ankylosing spondylitis in
      the vertebrae of the tail. Both C3H.Q and B10.Q mice deficient for B cells were
      resistant to arthritis. We conclude that G6PI has the ability to induce a chronic
      arthritis, which is MHC associated and B-cell dependent. Thus, there are striking
      similarities between this and the collagen-induced arthritis model.

PMID- 16277686
TI  - Contrasting effects of peroxisome-proliferator-activated receptor (PPAR)gamma
      agonists on membrane-associated prostaglandin E2 synthase-1 in IL-1beta
      stimulated rat chondrocytes: evidence for PPARgamma-independent inhibition by 15
      deoxy-Delta12,14prostaglandin J2.
AB  - Microsomal prostaglandin E synthase (mPGES)-1 is a newly identified inducible
      enzyme of the arachidonic acid cascade with a key function in prostaglandin
      (PG)E2 synthesis. We investigated the kinetics of inducible cyclo-oxygenase (COX)
      2 and mPGES-1 expression with respect to the production of 6-keto-PGF1alpha and
      PGE2 in rat chondrocytes stimulated with 10 ng/ml IL-1beta, and compared their
      modulation by peroxisome-proliferator-activated receptor (PPAR)gamma agonists.
      Real-time PCR analysis showed that IL-1beta induced COX-2 expression maximally
      (37-fold) at 12 hours and mPGES-1 expression maximally (68-fold) at 24 hours.
      Levels of 6-keto-PGF1alpha and PGE2 peaked 24 hours after stimulation with IL
      1beta; the induction of PGE2 was greater (11-fold versus 70-fold, respectively).
      The cyclopentenone 15-deoxy-Delta12,14prostaglandin J2 (15d-PGJ2) decreased
      prostaglandin synthesis in a dose-dependent manner (0.1 to 10 microM), with more
      potency on PGE2 level than on 6-keto-PGF1alpha level (-90% versus -66% at 10
      microM). A high dose of 15d-PGJ2 partly decreased COX-2 expression but decreased
      mPGES-1 expression almost completely at both the mRNA and protein levels.
      Rosiglitazone was poorly effective on these parameters even at 10 microM.
      Inhibitory effects of 10 microM 15d-PGJ2 were neither reduced by PPARgamma
      blockade with GW-9662 nor enhanced by PPARgamma overexpression, supporting a
      PPARgamma-independent mechanism. EMSA and TransAM analyses demonstrated that
      mutated IkappaBalpha almost completely suppressed the stimulating effect of IL
      1beta on mPGES-1 expression and PGE2 production, whereas 15d-PGJ2 inhibited NF
      kappaB transactivation. These data demonstrate the following in IL-1-stimulated
      rat chondrocytes: first, mPGES-1 is rate limiting for PGE2 synthesis; second,
      activation of the prostaglandin cascade requires NF-kappaB activation; third, 15d
      PGJ2 strongly inhibits the synthesis of prostaglandins, in contrast with
      rosiglitazone; fourth, inhibition by 15d-PGJ2 occurs independently of PPARgamma
      through inhibition of the NF-kappaB pathway; fifth, mPGES-1 is the main target of
      15d-PGJ2.

PMID- 16277688
TI  - Effect of a small molecule inhibitor of nuclear factor-kappaB nuclear
      translocation in a murine model of arthritis and cultured human synovial cells.
AB  - A small cell-permeable compound, dehydroxymethylepoxyquinomicin (DHMEQ), does not
      inhibit phosphorylation and degradation of IkappaB (inhibitor of nuclear factor
      kappaB [NF-kappaB]) but selectively inhibits nuclear translocation of activated
      NF-kappaB. This study aimed to demonstrate the antiarthritic effect of this novel
      inhibitor of the NF-kappaB pathway in vivo in a murine arthritis model and in
      vitro in human synovial cells. Collagen-induced arthritis was induced in mice,
      and after onset of arthritis the mice were treated with DHMEQ (5 mg/kg body
      weight per day). Using fibroblast-like synoviocyte (FLS) cell lines established
      from patients with rheumatoid arthritis (RA), NF-kappaB activity was examined by
      electrophoretic mobility shift assays. The expression of molecules involved in RA
      pathogenesis was determined by RT-PCR, ELISA, and flow cytometry. The
      proliferative activity of the cells was estimated with tritiated thymidine
      incorporation. After 14 days of treatment with DHMEQ, mice with collagen-induced
      arthritis exhibited decreased severity of arthritis, based on the degree of paw
      swelling, the number of swollen joints, and radiographic and histopathologic
      scores, compared with the control mice treated with vehicle alone. In RA FLS
      stimulated with tumor necrosis factor-alpha, activities of NF-kappaB components
      p65 and p50 were inhibited by DHMEQ, leading to suppressed expression of the key
      inflammatory cytokine IL-6, CC chemokine ligand-2 and -5, matrix
      metalloproteinase-3, intercellular adhesion molecule-1, and vascular cell
      adhesion molecule-1. The proliferative activity of the cells was also suppressed.
      This is the first demonstration of an inhibitor of NF-kappaB nuclear
      translocation exhibiting a therapeutic effect on established murine arthritis,
      and suppression of inflammatory mediators in FLS was thought to be among the
      mechanisms underlying such an effect.

PMID- 16277687
TI  - Reduced transforming growth factor-beta signaling in cartilage of old mice: role
      in impaired repair capacity.
AB  - Osteoarthritis (OA) is a common joint disease, mainly effecting the elderly
      population. The cause of OA seems to be an imbalance in catabolic and anabolic
      factors that develops with age. IL-1 is a catabolic factor known to induce
      cartilage damage, and transforming growth factor (TGF)-beta is an anabolic factor
      that can counteract many IL-1-induced effects. In old mice, we observed reduced
      responsiveness to TGF-beta-induced IL-1 counteraction. We investigated whether
      expression of TGF-beta and its signaling molecules altered with age. To mimic the
      TGF-beta deprived conditions in aged mice, we assessed the functional consequence
      of TGF-beta blocking. We isolated knee joints of mice aged 5 months or 2 years,
      half of which were exposed to IL-1 by intra-articular injection 24 h prior to
      knee joint isolation. Immunohistochemistry was performed, staining for TGF-beta1,
      -2 or -3, TGF-betaRI or -RII, Smad2, -3, -4, -6 and -7 and Smad-2P. The
      percentage of cells staining positive was determined in tibial cartilage. To
      mimic the lack of TGF-beta signaling in old mice, young mice were injected with
      IL-1 and after 2 days Ad-LAP (TGF-beta inhibitor) or a control virus were
      injected. Proteoglycan (PG) synthesis (35S-sulfate incorporation) and PG content
      of the cartilage were determined. Our experiments revealed that TGF-beta2 and -3
      expression decreased with age, as did the TGF-beta receptors. Although the number
      of cells positive for the Smad proteins was not altered, the number of cells
      expressing Smad2P strongly dropped in old mice. IL-1 did not alter the expression
      patterns. We mimicked the lack of TGF-beta signaling in old mice by TGF-beta
      inhibition with LAP. This resulted in a reduced level of PG synthesis and
      aggravation of PG depletion. The limited response of old mice to TGF-beta induced
      IL-1 counteraction is not due to a diminished level of intracellular signaling
      molecules or an upregulation of intracellular inhibitors, but is likely due to an
      intrinsic absence of sufficient TGF-beta receptor expression. Blocking TGF-beta
      distorted the natural repair response after IL-1 injection. In conclusion, TGF
      beta appears to play an important role in repair of cartilage and a lack of TGF
      beta responsiveness in old mice might be at the root of OA development.

PMID- 16277689
TI  - Most nuclear systemic autoantigens are extremely disordered proteins:
      implications for the etiology of systemic autoimmunity.
AB  - Patients with systemic autoimmune diseases usually produce high levels of
      antibodies to self-antigens (autoantigens). The repertoire of common autoantigens
      is remarkably limited, yet no readily understandable shared thread links these
      apparently diverse proteins. Using computer prediction algorithms, we have found
      that most nuclear systemic autoantigens are predicted to contain long regions of
      extreme structural disorder. Such disordered regions would generally make poor B
      cell epitopes and are predicted to be under-represented as potential T cell
      epitopes. Consideration of the potential role of protein disorder may give novel
      insights into the possible role of molecular mimicry in the pathogenesis of
      autoimmunity. The recognition of extreme autoantigen protein disorder has led us
      to an explicit model of epitope spreading that explains many of the paradoxical
      aspects of autoimmunity - in particular, the difficulty in identifying
      autoantigen-specific helper T cells that might collaborate with the B cells
      activated in systemic autoimmunity. The model also explains the experimentally
      observed breakdown of major histocompatibility complex (MHC) class specificity in
      peptides associated with the MHC II proteins of activated autoimmune B cells, and
      sheds light on the selection of particular T cell epitopes in autoimmunity.
      Finally, the model helps to rationalize the relative rarity of clinically
      significant autoimmunity despite the prevalence of low specificity/low avidity
      autoantibodies in normal individuals.

PMID- 16277690
TI  - Reproducibility and sensitivity to change of various methods to measure joint
      space width in osteoarthritis of the hip: a double reading of three different
      radiographic views taken with a three-year interval.
AB  - Joint space width (JSW) and narrowing (JSN) measurements on radiographs are
      currently the best way to assess disease severity or progression in hip
      osteoarthritis, yet we lack data regarding the most accurate and sensitive
      measurement technique. This study was conducted to determine the optimal
      radiograph and number of readers for measuring JSW and JSN. Fifty pairs of
      radiographs taken three years apart were obtained from patients included in a
      structure modification trial in hip osteoarthritis. Three radiographs were taken
      with the patient standing: pelvis, target hip anteroposterior (AP) and oblique
      views. Two trained readers, blinded to each other's findings, time sequence and
      treatment, each read the six radiographs gathered for each patient twice (time
      interval > or = 15 days), using a 0.1 mm graduated magnifying glass. Radiographs
      were randomly coded for each reading. The interobserver and intraobserver cross
      sectional (M0 and M36) and longitudinal (M0-M36) reproducibilities were assessed
      using the intraclass coefficient (ICC) and Bland-Altman method for readers 1 and
      2 and their mean. Sensitivity to change was estimated using the standardized
      response mean (SRM = change/standard deviation of change) for M0-M36 changes. For
      interobserver reliability on M0-M36 changes, the ICCs (95% confidence interval
      [CI]) were 0.79 (0.65-0.88) for pelvic view, 0.87 (0.78-0.93) for hip AP view and
      0.86 (0.76-0.92) for oblique view. Intraobserver reliability ICCs were 0.81 (0.69
      0.89) for observer 1 and 0.97 (0.95-0.98) for observer 2 for the pelvic view;
      0.87 (0.78-0.92) and 0.97 (0.96-0.99) for the hip AP view; and 0.73 (0.57-0.84)
      and 0.93 (0.88-0.96) for the oblique view. SRMs were 0.61 (observer 1) and 0.82
      (observer 2) for pelvic view; 0.64 and 0.75 for hip AP view; and 0.77 and 0.70
      for oblique view. All three views yielded accurate JSW and JSN. According to the
      best reader, the pelvic view performed slightly better. Both readers exhibited
      high precision, with SRMs of 0.6 or greater for assessing JSN over three years.
      Selecting a single reader was the most accurate method, with 0.3 mm precision.
      Using this cutoff, 50% of patients were classified as 'progressors'.

PMID- 16277691
TI  - The impact of HLA-DRB1 genes on extra-articular disease manifestations in
      rheumatoid arthritis.
AB  - The objective of this study was to examine HLA-DRB1 and HLA-DQB1 genotypes in
      patients with severe extra-articular rheumatoid arthritis (ExRA) and to compare
      them with the genotypes of rheumatoid arthritis (RA) patients without extra
      articular manifestations. Patients with severe ExRA were recruited from a large
      research database of patients with RA, from two cohorts of prevalent RA cases,
      and from a regional multicenter early RA cohort. Cases with ExRA manifestations
      (n = 159) were classified according to predefined criteria. Controls (n = 178)
      with RA but no ExRA were selected from the same sources. Cases and controls were
      matched for duration of RA and for clinical center. PCR based HLA-DRB1 and HLA
      DQB1 genotyping was performed using the Biotest SSP kit, with additional
      sequencing in order to distinguish DRB1*04 subtypes. Associations between alleles
      and disease phenotypes were tested using multiple simulations of random
      distributions of alleles. There was no difference in global distribution of HLA
      DRB1 and HLA-DQB1 alleles between patients with ExRA and controls. DRB1*0401 (P =
      0.003) and 0401/0401 homozygosity (P = 0.002) were more frequent in Felty's
      syndrome than in controls. The presence of two HLA-DRB1*04 alleles encoding the
      shared epitope (SE) was associated with ExRA (overall odds ratio 1.79, 95%
      confidence interval 1.04-3.08) and with rheumatoid vasculitis (odds ratio 2.44,
      95% confidence interval 1.22-4.89). In this large sample of patients with ExRA,
      Felty's syndrome was the only manifestation that was clearly associated with HLA
      DRB1*0401. Other ExRA manifestations were not associated with individual alleles
      but with DRB1*04 SE double dose genotypes. This confirms that SE genes contribute
      to RA disease severity and ExRA. Other genetic and environmental factors may have
      a more specific impact on individual ExRA manifestations.

PMID- 16277692
TI  - Association between anti-nucleophosmin and anti-cardiolipin antibodies in (NZW x
      BXSB)F1 mice and human systemic lupus erythematosus.
AB  - We showed previously that nucleophosmin (NPM), a nucleolar phosphoprotein, is
      recognized by sera from (NZW x BXSB)F1 (WB) mice, a model of systemic lupus
      erythematosus (SLE) and anti-phospholipid syndrome. In the present study we
      analysed the prevalence and kinetics of anti-NPM autoantibodies in WB mice by a
      solid-phase ELISA with recombinant human (rh) NPM as the antigen and showed that
      most male WB mouse sera had anti-NPM antibodies that were responsible for their
      indirect immunofluorescence staining pattern on Hep-2 cells. Anti-NPM antibodies
      were significantly associated with anti-cardiolipin (aCL) antibodies. This
      antibody profile mirrored that observed in certain human SLE sera because anti
      NPM antibodies were detected in 28% of the sera from patients with SLE and were
      similarly associated with aCL antibodies. The demonstration that rhNPM bound to
      cardiolipin (CL) in vitro and increased the CL-binding activity of a WB-derived
      aCL monoclonal antibody indicates that NPM can interact with CL to form SLE
      related immunogenic particles that might be responsible for the concomitant
      production of anti-NPM and aCL antibodies.

PMID- 16277693
TI  - Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve
      inflammation in patients with rheumatoid arthritis.
AB  - Patients with rheumatoid arthritis have subnormal vitamin B6 status, both
      quantitatively and functionally. Abnormal vitamin B6 status in rheumatoid
      arthritis has been associated with spontaneous tumor necrosis factor (TNF)-alpha
      production and markers of inflammation, including C-reactive protein and
      erythrocyte sedimentation rate. Impaired vitamin B6 status could be a result of
      inflammation, and these patients may have higher demand for vitamin B6. The aim
      of this study was to determine if daily supplementation with 50 mg of pyridoxine
      for 30 days can correct the static and/or the functional abnormalities of vitamin
      B6 status seen in patients with rheumatoid arthritis, and further investigate if
      pyridoxine supplementation has any effects on the pro-inflammatory cytokine TNF
      alpha or IL-6 production of arthritis. This was a double-blinded, placebo
      controlled study involving patients with rheumatoid arthritis with plasma
      pyridoxal 5'-phosphate below the 25th percentile of the Framingham Heart Cohort
      Study. Vitamin B6 status was assessed via plasma and erythrocyte pyridoxal 5'
      phosphate concentrations, the erythrocyte aspartate aminotransferase activity
      coefficient (alphaEAST), net homocysteine increase in response to a methionine
      load test (DeltatHcy), and 24 h urinary xanthurenic acid (XA) excretion in
      response to a tryptophan load test. Urinary 4-pyridoxic acid (4-PA) was measured
      to examine the impact of pyridoxine treatment on vitamin B6 excretion in these
      patients. Pro-inflammatory cytokine (TNF-alpha and IL-6) production, C-reactive
      protein levels and the erythrocyte sedimentation rate before and after
      supplementation were also examined. Pyridoxine supplementation significantly
      improved plasma and erythrocyte pyridoxal 5'-phosphate concentrations,
      erythrocyte alphaEAST, urinary 4-PA, and XA excretion. These improvements were
      apparent regardless of baseline B6 levels. Pyridoxine supplementation also showed
      a trend (p < 0.09) towards a reduction in post-methionine load DeltatHcy.
      Supplementation did not affect pro-inflammatory cytokine production. Although
      pyridoxine supplementation did not suppress pro-inflammatory cytokine production
      in patients with rheumatoid arthritis, the suboptimal vitamin B6 status seen in
      rheumatoid arthritis can be corrected by 50 mg pyridoxine supplementation for 30
      days. Data from the present study suggest that patients with rheumatoid arthritis
      may have higher requirements for vitamin B6 than those in a normal healthy
      population.

PMID- 16277696
TI  - Gene therapy for arthritis--where do we stand?
AB  - The successful use of biologicals in the treatment of rheumatoid arthritis,
      psoriatic arthritis and spondyloarthritis has had a major impact on the
      management of these conditions. The challenge in the development of gene therapy
      as an alternative to these current treatments is to demonstrate that such therapy
      is more advantageous for patients from the therapeutic and safety points of view.
      Also, it will need to be demonstrated that gene therapy for the arthritides is
      economically feasible and that patient populations worldwide will be able to
      access these treatments.

PMID- 16277694
TI  - Between adaptive and innate immunity: TLR4-mediated perforin production by
      CD28null T-helper cells in ankylosing spondylitis.
AB  - CD3+CD4+CD28null and CD3+CD8+CD28null T cells are enriched in patients with
      immune-mediated diseases compared with healthy controls. This study shows that
      CD4+CD28null T cells express Toll-like receptors recognizing bacterial
      lipopolysaccharides in ankylosing spondylitis, psoriatic arthritis and rheumatoid
      arthritis. In ankylosing spondylitis, TLR4 (23.1 +/- 21.9%) and, to a smaller
      extent, TLR2 (4.1 +/- 5.8%) were expressed on CD4+CD28null T cells, whereas
      expression was negligible on CD4+CD28+ and CD8+ T cells. CD4+CD28null T cells
      produced perforin upon stimulation with lipopolysaccharide, and this effect was
      enhanced by autologous serum or recombinant soluble CD14. Perforin production
      could be prevented with blocking antibodies directed against CD14 or TLR4.
      Incubation of peripheral blood mononuclear cells with tumour necrosis factor
      alpha led to an upregulation of TLR4 and TLR2 on CD4+CD28null T cells in vitro,
      and treatment of patients with antibodies specifically directed against tumour
      necrosis factor alpha resulted in decreased expression of TLR4 and TLR2 on
      CD4+CD28null T cells in vivo. We describe here a new pathway for direct
      activation of cytotoxic CD4+ T cells by components of infectious pathogens. This
      finding supports the hypothesis that CD4+CD28null T cells represent an
      immunological link between the innate immune system and the adaptive immune
      system.

PMID- 16277695
TI  - Identification of citrullinated alpha-enolase as a candidate autoantigen in
      rheumatoid arthritis.
AB  - Antibodies against citrullinated proteins are highly specific for rheumatoid
      arthritis (RA), but little is understood about their citrullinated target
      antigens. We have detected a candidate citrullinated protein by immunoblotting
      lysates of monocytic and granulocytic HL-60 cells treated with peptidylarginine
      deiminase. In an initial screen of serum samples from four patients with RA and
      one control, a protein of molecular mass 47 kDa from monocytic HL-60s reacted
      with sera from the patients, but not with the serum from the control. Only the
      citrullinated form of the protein was recognised. The antigen was identified by
      tandem mass spectrometry as alpha-enolase, and the positions of nine citrulline
      residues in the sequence were determined. Serum samples from 52 patients with RA
      and 40 healthy controls were tested for presence of antibodies against
      citrullinated and non-citrullinated alpha-enolase by immunoblotting of the
      purified antigens. Twenty-four sera from patients with RA (46%) reacted with
      citrullinated alpha-enolase, of which seven (13%) also recognised the non
      citrullinated protein. Six samples from the controls (15%) reacted with both
      forms. Alpha-enolase was detected in the RA joint, where it co-localised with
      citrullinated proteins. The presence of antibody together with expression of
      antigen within the joint implicates citrullinated alpha-enolase as a candidate
      autoantigen that could drive the chronic inflammatory response in RA.

PMID- 16277697
TI  - Does a positive anti-CCP test identify a distinct arthritis entity?
AB  - The introduction of tests recognizing 'anti-citrullinated protein antibodies'
      (ACPA) has caused a revolution in rheumatology. Immunization against
      citrullinated proteins is a feature almost unique for rheumatoid arthritis,
      although ACPA may occur long before the onset of symptoms. Even if the presence
      of ACPA does not seem to reveal a distinct arthritis phenotype at symptom onset,
      it predicts an aggressive disease course with unfavourable outcome. Despite the
      very high diagnostic specificity for rheumatoid arthritis, ACPA-positivity does
      not always accord with a traditional diagnosis of rheumatoid arthritis at
      clinical presentation. However, even when these patients are judged to suffer
      from mild undifferentiated arthritis, they call for follow-up and special
      attention by rheumatologists.

PMID- 16277699
TI  - Can magnetic resonance imaging differentiate undifferentiated arthritis?
AB  - A high sensitivity for the detection of inflammatory and destructive changes in
      inflammatory joint diseases makes magnetic resonance imaging potentially useful
      for assigning specific diagnoses, such as rheumatoid arthritis and psoriatic
      arthritis in arthritides, that remain undifferentiated after conventional
      clinical, biochemical and radiographic examinations. With recent data as the
      starting point, the present paper describes the current knowledge on magnetic
      resonance imaging in the differential diagnosis of undifferentiated arthritis.

PMID- 16277698
TI  - E3 ubiquitin ligases and their control of T cell autoreactivity.
AB  - A loss of T cell tolerance underlies the development of most autoimmune diseases.
      The design of therapeutic strategies to reinstitute immune tolerance, however, is
      hampered by uncertainty regarding the molecular mechanisms involved in the
      inactivation of potentially autoreactive T cells. Recently, E3 ubiquitin ligases
      have been shown to mediate the development of a durable state of unresponsiveness
      in T cells called clonal anergy. In this review, we will discuss the mechanisms
      used by E3 ligases to control the activation of T cells and prevent the
      development of autoimmunity.

PMID- 16277700
TI  - Application of in vivo microscopy: evaluating the immune response in living
      animals.
AB  - The initiation of an immune response requires that professional antigen
      presenting cells, such as dendritic cells, physically interact with antigen
      specific T cells within the complex environment of the lymph node. Although the
      way in which antigen is presented to T cells and in particular the cellular
      associations involved in antigen-specific stimulation events have been
      extensively investigated, data on antigen presentation have come primarily from
      studies in vitro or examination of the late consequences of antigen presentation
      in vivo. However, there is increasing recognition that events defined in vitro
      might not correspond entirely to the physiological situation in vivo. Recent
      developments in imaging technology now allow real-time observation of single-cell
      and molecular interactions in intact lymphoid tissues and have already
      contributed to a more detailed picture of how cells coordinate the initiation or
      suppression of an immune response.

PMID- 16277702
TI  - It's all in the blood: circulating endothelial progenitor cells link synovial
      vascularity with cardiovascular mortality in rheumatoid arthritis?

PMID- 16277701
TI  - Dipeptidyl peptidase IV activity and/or structure homologs: contributing factors
      in the pathogenesis of rheumatoid arthritis?
AB  - Several of the proinflammatory peptides involved in rheumatoid arthritis
      pathogenesis, including peptides induced downstream of tumor necrosis factor
      alpha as well as the monocyte/T cell-attracting chemokines RANTES and stromal
      cell-derived factor (SDF)-1alpha and the neuropeptides vasoactive intestinal
      peptide (VIP) and substance P, have their biological half-lives controlled by
      dipeptidyl peptidase IV (DPPIV). Proteolysis by DPPIV regulates not only the half
      life but also receptor preference and downstream signaling. In this article, we
      examine the role of DPPIV homologs, including CD26, the canonical DPPIV, and
      their substrates in the pathogenesis of rheumatoid arthritis. The differing
      specific activities of the DPPIV family members and their differential inhibitor
      response provide new insights into therapeutic design.

PMID- 16277703
TI  - The 3rd International Meeting on Gene Therapy in Rheumatology and Orthopaedics.
AB  - The 3rd International Meeting on Gene Therapy in Rheumatology and Orthopaedics
      was held in Boston, Massachusetts, USA in May 2004. Keystone lectures delivered
      by Drs Joseph Glorioso and Inder Verma provided comprehensive, up-to-date
      information on all major virus vectors. Other invited speakers covered the
      application of gene therapy to treatment of arthritis, including the latest
      clinical trial in rheumatoid arthritis, as well as lupus and Sjogren's syndrome.
      Applications in mesenchymal stem cell biology, tissue repair, and regenerative
      medicine were also addressed. The field has advanced considerably since the
      previous meeting in this series, and further clinical trials seem likely.

PMID- 16277705
TI  - Corticosteroids increased short and long-term mortality in adults with traumatic
      head injury.

PMID- 16277704
TI  - Afelimomab led to a modest mortality benefit in patients with severe sepsis and
      elevated interleukin-6 levels.

PMID- 16277706
TI  - eICU program favorably affects clinical and economic outcomes.

PMID- 16277707
TI  - Krebs cycle anions in metabolic acidosis.
AB  - For many years it has been apparent from estimates of the anion gap and the
      strong ion gap that anions of unknown identity can be generated in sepsis and
      shock states. Evidence is emerging that at least some of these are intermediates
      of the citric acid cycle. The exact source of this disturbance remains unclear,
      because a great many metabolic blocks and bottlenecks can disturb the anaplerotic
      and cataplerotic pathways that enter and leave the cycle. These mechanisms
      require clarification with the use of tools such as gas chromatography-mass
      spectrometry.

PMID- 16277708
TI  - Respiratory compliance but not gas exchange correlates with changes in lung
      aeration after a recruitment maneuver: an experimental study in pigs with saline
      lavage lung injury.
AB  - INTRODUCTION: Atelectasis is a common finding in acute lung injury, leading to
      increased shunt and hypoxemia. Current treatment strategies aim to recruit
      alveoli for gas exchange. Improvement in oxygenation is commonly used to detect
      recruitment, although the assumption that gas exchange parameters adequately
      represent the mechanical process of alveolar opening has not been proven so far.
      The aim of this study was to investigate whether commonly used measures of lung
      mechanics better detect lung tissue collapse and changes in lung aeration after a
      recruitment maneuver as compared to measures of gas exchange METHODS: In eight
      anesthetized and mechanically ventilated pigs, acute lung injury was induced by
      saline lavage and a recruitment maneuver was performed by inflating the lungs
      three times with a pressure of 45 cmH2O for 40 s with a constant positive end
      expiratory pressure of 10 cmH2O. The association of gas exchange and lung
      mechanics parameters with the amount and the changes in aerated and nonaerated
      lung volumes induced by this specific recruitment maneuver was investigated by
      multi slice CT scan analysis of the whole lung. RESULTS: Nonaerated lung
      correlated with shunt fraction (r = 0.68) and respiratory system compliance (r =
      0.59). The arterial partial oxygen pressure (PaO2) and the respiratory system
      compliance correlated with poorly aerated lung volume (r = 0.57 and 0.72,
      respectively). The recruitment maneuver caused a decrease in nonaerated lung
      volume, an increase in normally and poorly aerated lung, but no change in the
      distribution of a tidal breath to differently aerated lung volumes. The
      fractional changes in PaO2, arterial partial carbon dioxide pressure (PaCO2) and
      venous admixture after the recruitment maneuver did not correlate with the
      changes in lung volumes. Alveolar recruitment correlated only with changes in the
      plateau pressure (r = 0.89), respiratory system compliance (r = 0.82) and
      parameters obtained from the pressure-volume curve. CONCLUSION: A recruitment
      maneuver by repeatedly hyperinflating the lungs led to an increase of poorly
      aerated and a decrease of nonaerated lung mainly. Changes in aerated and
      nonaerated lung volumes were adequately represented by respiratory compliance but
      not by changes in oxygenation or shunt.

PMID- 16277709
TI  - Mannan-binding lectin and procalcitonin measurement for prediction of
      postoperative infection.
AB  - INTRODUCTION: Postoperative infection is a major cause of morbidity and
      mortality. We investigated two serum markers for their ability to identify
      patients at risk for postoperative infection. Mannan-binding lectin (MBL) is a
      central molecule of the innate immune system and MBL deficiency is known to
      predispose to infection. Procalcitonin (PCT) is a sensitive marker for bacterial
      infection. METHODS: We investigated 162 patients undergoing elective surgery for
      cancer of the gastrointestinal tract. Patients were classified as having no
      complications (group A), having infection for unknown reason (group B) or having
      sepsis after events like aspiration or anastomotic leakage (group C). Analysis
      was done pre- and postoperatively for serum levels of MBL, PCT and C-reactive
      protein. DNA was preoperatively sampled and stored and later analysed for genetic
      polymorphisms of MBL. RESULTS: The preoperative serum levels of MBL were
      significantly lower in group B patients than in group A patients (1332 +/- 466
      ng/ml versus 2523 +/- 181 ng/ml). PCT measured on day one post-surgery was
      significantly higher in group B patients than in group A (3.33 +/- 1.08 ng/ml
      versus 1.38 +/- 0.17 ng/ml). Patients with an aberrant MBL genotype had a
      significantly higher risk of postoperative infections than wild-type carriers (p
      < 0.05). CONCLUSION: Preoperative MBL and early postoperative PCT measurement may
      help identify patients at risk for postoperative infection.

PMID- 16277710
TI  - Recombinant human activated protein C resets thrombin generation in patients with
      severe sepsis - a case control study.
AB  - INTRODUCTION: Recombinant human activated protein C (rhAPC) is the first drug for
      which a reduction of mortality in severe sepsis has been demonstrated. However,
      the mechanism by which this reduction in mortality is achieved is still not
      clearly defined. The aim of the present study was to evaluate the dynamics of the
      anticoagulant, anti-inflammatory and pro-fibrinolytic action of rhAPC in patients
      with severe sepsis, by comparing rhAPC-treated patients with case controls.
      METHODS: In this prospectively designed multicenter case control study, 12
      patients who were participating in the ENHANCE study, an open-label study of
      rhAPC in severe sepsis, were treated intravenously with rhAPC at a constant rate
      of 24 microg/kg/h for a total of 96 h. Twelve controls with severe sepsis
      matching the inclusion criteria received standard therapy. The treatment was
      started within 48 h after the onset of organ failure. Blood samples were taken
      before the start of the infusion and at 4, 8, 24, 48, 96 and 168 h, for
      determination of parameters of coagulation and inflammation. RESULTS: Sepsis
      induced thrombin generation as measured by thrombin-antithrombin complexes and
      prothrombin fragment F1+2, was reset by rhAPC within the first 8 h of infusion.
      The administration of rhAPC did not influence parameters of fibrinolysis and
      inflammation. There was no difference in outcome or occurrence of serious adverse
      events between the treatment group and the control group. CONCLUSION: Sepsis
      induced thrombin generation in severely septic patients is reset by rhAPC within
      the first 8 h of infusion without influencing parameters of fibrinolysis and
      inflammation.

PMID- 16277711
TI  - Steroid use in PROWESS severe sepsis patients treated with drotrecogin alfa
      (activated).
AB  - INTRODUCTION: In a study conducted by Annane, patients with septic shock and
      unresponsive to adrenocorticotropic hormone stimulation receiving low-dose
      steroid therapy had prolonged survival but not significantly improved 28-day
      mortality. The present study examines intravenous steroid use in PROWESS
      (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis)
      patients meeting the Annane enrollment criteria (AEC). METHODS:
      Adrenocorticotropic hormone stimulation tests were not done in PROWESS. Steroids
      were allowed but their use was not directed. Patients were identified using AEC
      (all of: randomization to study drug treatment within 8 hours of shock onset;
      infection, fever, or hypothermia; tachycardia; systolic blood pressure <90 mmHg
      on vasopressors; mechanical ventilation; and one of urine <0.5 ml/kg per hour,
      lactic acidosis, or arterial oxygen tension/inspired fractional oxygen <280). We
      examined steroid use and mortality data; additional analyses were done outside
      the 8-hour window. RESULTS: Steroid-treated patients were older, had higher Acute
      Physiology and Chronic Health Evaluation scores and more organ dysfunctions, and
      were more commonly receiving mechanical ventilation. Among patients meeting AEC,
      regardless of steroid treatment (n = 97), mortality in the placebo and
      drotrecogin alfa (activated) groups was 38% (19/50) and 28% (13/47), respectively
      (relative risk [RR] = 0.73, 95% confidence interval [CI] 0.41-1.30). When using
      AEC but excluding the requirement for randomization within 8 hours of shock onset
      (n = 612), placebo mortality was 38% (118/313) and drotrecogin alfa (activated)
      mortality was 29% (88/299; RR = 0.78, 95% CI 0.62-0.98). Using AEC but excluding
      the 8-hour window and with steroids initiated at baseline and/or infusion (n =
      228) resulted in mortality for placebo and drotrecogin alfa (activated) groups of
      43% (51/118) and 33% (36/110), respectively (RR = 0.76, 95% CI 0.54-1.06).
      CONCLUSION: Patients with severe sepsis from the PROWESS trial who were likely to
      respond to low-dose steroids according to the AEC were those patients at a high
      risk for death. However, when using the AEC, regardless of steroid use, patients
      exhibited a survival benefit from treatment with drotrecogin alfa (activated).

PMID- 16277712
TI  - Recombinant human erythropoietin therapy in critically ill patients: a dose
      response study [ISRCTN48523317].
AB  - INTRODUCTION: The aim of this study was to assess the efficacy of two dosing
      schedules of recombinant human erythropoietin (rHuEPO) in increasing haematocrit
      (Hct) and haemoglobin (Hb) and reducing exposure to allogeneic red blood cell
      (RBC) transfusion in critically ill patients. METHOD: This was a prospective,
      randomized, multicentre trial. A total of 13 intensive care units participated,
      and a total of 148 patients who met eligibility criteria were enrolled. Patients
      were randomly assigned to receive intravenous iron saccharate alone (control
      group), intravenous iron saccharate and subcutaneous rHuEPO 40,000 units once per
      week (group A), or intravenous iron saccharate and subcutaneous rHuEPO 40,000
      units three times per week (group B). rHuEPO was given for a minimum of 2 weeks
      or until discharge from the intensive care unit or death. The maximum duration of
      therapy was 3 weeks. RESULTS: The cumulative number of RBC units transfused, the
      average numbers of RBC units transfused per patient and per transfused patient,
      the average volume of RBCs transfused per day, and the percentage of transfused
      patients were significantly higher in the control group than in groups A and B.
      No significant difference was observed between group A and B. The mean increases
      in Hct and Hb from baseline to final measurement were significantly greater in
      group B than in the control group. The mean increase in Hct was significantly
      greater in group B than in group A. The mean increase in Hct in group A was
      significantly greater than that in control individuals, whereas the mean increase
      in Hb did not differ significantly between the control group and group A.
      CONCLUSION: Administration of rHuEPO to critically ill patients significantly
      reduced the need for RBC transfusion. The magnitude of the reduction did not
      differ between the two dosing schedules, although there was a dose response for
      Hct and Hb to rHuEPO in these patients.

PMID- 16277713
TI  - Medication errors: a prospective cohort study of hand-written and computerised
      physician order entry in the intensive care unit.
AB  - INTRODUCTION: The study aimed to compare the impact of computerised physician
      order entry (CPOE) without decision support with hand-written prescribing (HWP)
      on the frequency, type and outcome of medication errors (MEs) in the intensive
      care unit. METHODS: Details of MEs were collected before, and at several time
      points after, the change from HWP to CPOE. The study was conducted in a London
      teaching hospital's 22-bedded general ICU. The sampling periods were 28 weeks
      before and 2, 10, 25 and 37 weeks after introduction of CPOE. The unit pharmacist
      prospectively recorded details of MEs and the total number of drugs prescribed
      daily during the data collection periods, during the course of his normal chart
      review. RESULTS: The total proportion of MEs was significantly lower with CPOE
      (117 errors from 2429 prescriptions, 4.8%) than with HWP (69 errors from 1036
      prescriptions, 6.7%) (p < 0.04). The proportion of errors reduced with time
      following the introduction of CPOE (p < 0.001). Two errors with CPOE led to
      patient harm requiring an increase in length of stay and, if administered, three
      prescriptions with CPOE could potentially have led to permanent harm or death.
      Differences in the types of error between systems were noted. There was a
      reduction in major/moderate patient outcomes with CPOE when non-intercepted and
      intercepted errors were combined (p = 0.01). The mean baseline APACHE II score
      did not differ significantly between the HWP and the CPOE periods (19.4 versus
      20.0, respectively, p = 0.71). CONCLUSION: Introduction of CPOE was associated
      with a reduction in the proportion of MEs and an improvement in the overall
      patient outcome score (if intercepted errors were included). Moderate and major
      errors, however, remain a significant concern with CPOE.

PMID- 16277714
TI  - Application of a population-based severity scoring system to individual patients
      results in frequent misclassification.
AB  - INTRODUCTION: APACHE II (AP2) was developed to allow a systematic examination of
      intensive care unit outcomes in a risk adjusted manner. AP2 has been widely
      adopted in clinical trials to assure broad consistency amongst different groups.
      Although errors in calculating the true AP2 score may not be reducible below 15%,
      the self-canceling effect of random errors reduces the importance of such errors
      when applied to large populations. It has been suggested that a threshold AP2
      score be used in clinical decision making for individual patients. This study
      reports the AP2 scoring errors of researchers involved in a large sepsis trial
      and models the consequences of such an error rate for individual severe sepsis
      patients. METHODS: Fifty-six researchers with explicit training in data
      abstraction and completion of the AP2 score received scenarios consisting of
      composites of real patient histories. Descriptive statistics were calculated for
      each scenario. The standard deviations were calculated compared with an
      adjudicated score. Intraclass correlations for inter-observer reliability were
      performed using Shrout-Fleiss methodology. Theoretical distribution curves were
      calculated for a broad range of AP2 scores using standard deviations of 6, 9 and
      12. For each curve, the misclassification rate was determined using an AP2 score
      cut-off of >or=25. The percentage of misclassifications for each true AP2 score
      was then applied to the corresponding AP2 score obtained from the PROGRESS severe
      sepsis registry. RESULTS: The error rate for the total AP2 score was 86%
      (individual variables were in the range 10% to 87%). Intraclass correlation for
      the inter-observer reliability was 0.51. Of the patients from the PROGRESS
      registry. 50% had AP2 scores in the range 17 to 28. Within this interquartile
      range, 70% to 85% of all misclassified patients would reside. CONCLUSION: It is
      more likely that an individual patient will be scored incorrectly than correctly.
      The data obtained from the scenarios indicated that as the true AP2 score
      approached an arbitrary cut-off point of 25, the observed misclassification rate
      increased. Integrating our study of AP2 score errors with the published
      literature leads us to conclude that the AP2 is an inappropriate sole tool for
      resource allocation decisions for individual patients.

PMID- 16277715
TI  - Efficiency of 7.2% hypertonic saline hydroxyethyl starch 200/0.5 versus mannitol
      15% in the treatment of increased intracranial pressure in neurosurgical patients
      - a randomized clinical trial [ISRCTN62699180].
AB  - INTRODUCTION: This prospective randomized clinical study investigated the
      efficacy and safety of 7.2% hypertonic saline hydroxyethyl starch 200/0.5 (7.2%
      NaCl/HES 200/0.5) in comparison with 15% mannitol in the treatment of increased
      intracranial pressure (ICP). METHODS: Forty neurosurgical patients at risk of
      increased ICP were randomized to receive either 7.2% NaCl/HES 200/0.5 or 15%
      mannitol at a defined infusion rate, which was stopped when ICP was < 15 mmHg.
      RESULTS: Of the 40 patients, 17 patients received 7.2% NaCl/HES 200/0.5 and 15
      received mannitol 15%. In eight patients, ICP did not exceed 20 mmHg so treatment
      was not necessary. Both drugs decreased ICP below 15 mmHg (p < 0.0001); 7.2%
      NaCl/HES 200/0.5 within 6.0 (1.2-15.0) min (all results are presented as median
      (minimum-maximum range)) and mannitol within 8.7 (4.2-19.9) min (p < 0.0002).
      7.2% NaCl/HES 200/0.5 caused a greater decrease in ICP than mannitol (57% vs 48%;
      p < 0.01). The cerebral perfusion pressure was increased from 60 (39-78) mmHg to
      72 (54-85) mmHg by infusion with 7.2% NaCl/HES 200/0.5 (p < 0.0001) and from 61
      (47-71) mmHg to 70 (50-79) mmHg with mannitol (p < 0.0001). The mean arterial
      pressure was increased by 3.7% during the infusion of 7.2% NaCl/HES 200/0.5 but
      was not altered by mannitol. There were no clinically relevant effects on
      electrolyte concentrations and osmolarity in the blood. The mean effective dose
      to achieve an ICP below 15 mmHg was 1.4 (0.3-3.1) ml/kg for 7.2% NaCl/HES 200/0.5
      and 1.8 (0.45-6.5) ml/kg for mannitol (p < 0.05). CONCLUSION: 7.2% NaCl/HES
      200/0.5 is more effective than mannitol 15% in the treatment of increased ICP. A
      dose of 1.4 ml/kg of 7.2% NaCl/HES 200/0.5 can be recommended as effective and
      safe. The advantage of 7.2% NaCl/HES 200/0.5 might be explained by local osmotic
      effects, because there were no clinically relevant differences in hemodynamic
      clinical chemistry parameters.

PMID- 16277716
TI  - Antifactor Xa activity in critically ill patients receiving antithrombotic
      prophylaxis with standard dosages of certoparin: a prospective, clinical study.
AB  - INTRODUCTION: Deep venous thrombosis with subsequent pulmonary embolism or post
      thrombotic syndrome is a feared complication in the intensive care unit.
      Therefore, routine prophylactic anticoagulation is widely recommended. Aside from
      unfractionated heparin, low molecular weight heparins, such as certoparin, have
      become increasingly used for prophylactic anticoagulation in critically ill
      patients. In this prospective study, we evaluated the potency of 3,000 IU
      certoparin administered once daily to reach antithrombotic antifactor Xa (aFXa)
      levels of 0.1 to 0.3 IU/ml in 62 critically ill patients. METHODS: AFXa levels
      were determined 4, 12 and 24 h after injection of certoparin. Prothrombin time,
      activated partial thromboplastin time, antithrombin, fibrinogen, hemoglobin,
      platelet count, serum urea and creatinine concentrations were documented before
      and 12 and 24 h after injection of certoparin. RESULTS: Four hours after
      certoparin injection (n = 32), 28% of patients were within the antithrombotic
      aFXa range. After 12 and 24 h, 6% achieved antithrombotic aFXa levels. Because of
      a severe pulmonary embolism in one study patient, an interim analysis was
      performed, and the dosage of certoparin was increased to 3,000 IU twice daily.
      This regime attained recommended antithrombotic aFXa levels in 47%, 27%, 40% and
      30% of patients at 4, 12, 16 and 24 h, respectively, after twice daily certoparin
      injection (n = 30). Antithrombin and fibrinogen concentrations slightly increased
      during the observation period. Low antithrombin concentrations before certoparin
      were independently correlated with underdosing of certoparin. Patients with aFXa
      levels <0.1 IU/ml 4 h after certoparin injection required vasopressors more often
      and had lower serum concentrations of creatinine and urea than patients with
      antithrombotic aFXa levels. CONCLUSION: Standard dosages of certoparin of 3,000
      IU given once or twice daily are ineffective for attaining the recommended aFXa
      levels of 0.1 to 0.3 IU/ml in critically ill patients. Low antithrombin levels
      before certoparin administration were independently associated with low aFXa
      levels. Renal function and vasopressor therapy may further influence the
      effectiveness of certoparin in ensuring adequate antithrombotic prophylaxis.

PMID- 16277717
TI  - Does cardiac surgery in newborn infants compromise blood cell reactivity to
      endotoxin?
AB  - INTRODUCTION: Neonatal cardiac surgery is associated with a systemic inflammatory
      reaction that might compromise the reactivity of blood cells against an
      inflammatory stimulus. Our prospective study was aimed at testing this
      hypothesis. METHODS: We investigated 17 newborn infants with transposition of the
      great arteries undergoing arterial switch operation. Ex vivo production of the
      pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), of the
      regulator of the acute-phase response IL-6, and of the natural anti-inflammatory
      cytokine IL-10 were measured by enzyme-linked immunosorbent assay in the cell
      culture supernatant after whole blood stimulation by the endotoxin
      lipopolysaccharide before, 5 and 10 days after the operation. Results were
      analyzed with respect to postoperative morbidity. RESULTS: The ex vivo production
      of TNF-alpha and IL-6 was significantly decreased (P < 0.001 and P < 0.002,
      respectively), whereas ex vivo production of IL-10 tended to be lower 5 days
      after the operation in comparison with preoperative values (P < 0.1). Ex vivo
      production of all cytokines reached preoperative values 10 days after cardiac
      surgery. Preoperative ex vivo production of IL-6 was inversely correlated with
      the postoperative oxygenation index 4 hours and 24 hours after the operation (P <
      0.02). In contrast, postoperative ex vivo production of cytokines did not
      correlate with postoperative morbidity. CONCLUSION: Our results show that cardiac
      surgery in newborn infants is associated with a transient but significant
      decrease in the ex vivo production of the pro-inflammatory cytokines TNF-alpha
      and IL-6 together with a less pronounced decrease in IL-10 production. This might
      indicate a transient postoperative anti-inflammatory shift of the cytokine
      balance in this age group. Our results suggest that higher preoperative ex vivo
      production of IL-6 is associated with a higher risk for postoperative pulmonary
      dysfunction.

PMID- 16277718
TI  - Urinary bladder partial carbon dioxide tension during hemorrhagic shock and
      reperfusion: an observational study.
AB  - INTRODUCTION: Continuous monitoring of bladder partial carbon dioxide tension
      (PCO2) using fibreoptic sensor technology may represent a useful means by which
      tissue perfusion may be monitored. In addition, its changes might parallel
      tonometric gut PCO2. Our hypothesis was that bladder PCO2, measured using saline
      tonometry, will be similar to ileal PCO2 during ischaemia and reperfusion.
      METHOD: Six anaesthetized and mechanically ventilated sheep were bled to a mean
      arterial blood pressure of 40 mmHg for 30 min (ischaemia). Then, blood was
      reinfused and measurements were repeated at 30 and 60 min (reperfusion). We
      measured systemic and gut oxygen delivery and consumption, lactate and various
      PCO2 gradients (urinary bladder-arterial, ileal-arterial, mixed venous-arterial
      and mesenteric venous-arterial). Both bladder and ileal PCO2 were measured using
      saline tonometry. RESULTS: After bleeding systemic and intestinal oxygen supply
      dependency and lactic acidosis ensued, along with elevations in PCO2 gradients
      when compared with baseline values (all values in mmHg; bladder DeltaPCO2 3 +/- 3
      versus 12 +/- 5, ileal DeltaPCO2 9 +/- 5 versus 29 +/- 16, mixed venous-arterial
      PCO2 5 +/- 1 versus 13 +/- 4, and mesenteric venous-arterial PCO2 4 +/- 2 versus
      14 +/- 4; P < 0.05 versus basal for all). After blood reinfusion, PCO2 gradients
      returned to basal values except for bladder DeltaPCO2, which remained at
      ischaemic levels (13 +/- 7 mmHg). CONCLUSION: Tissue and venous hypercapnia are
      ubiquitous events during low flow states. Tonometric bladder PCO2 might be a
      useful indicator of tissue hypoperfusion. In addition, the observed persistence
      of bladder hypercapnia after blood reinfusion may identify a territory that is
      more susceptible to reperfusion injury. The greatest increase in PCO2 gradients
      occurred in gut mucosa. Moreover, the fact that ileal DeltaPCO2 was greater than
      the mesenteric venous-arterial PCO2 suggests that tonometrically measured PCO2
      reflects mucosal rather than transmural PCO2. Ileal DeltaPCO2 appears to be the
      more sensitive marker of ischaemia.

PMID- 16277719
TI  - Relation between respiratory variations in pulse oximetry plethysmographic
      waveform amplitude and arterial pulse pressure in ventilated patients.
AB  - INTRODUCTION: Respiratory variation in arterial pulse pressure is a reliable
      predictor of fluid responsiveness in mechanically ventilated patients with
      circulatory failure. The main limitation of this method is that it requires an
      invasive arterial catheter. Both arterial and pulse oximetry plethysmographic
      waveforms depend on stroke volume. We conducted a prospective study to evaluate
      the relationship between respiratory variation in arterial pulse pressure and
      respiratory variation in pulse oximetry plethysmographic (POP) waveform
      amplitude. METHOD: This prospective clinical investigation was conducted in 22
      mechanically ventilated patients. Respiratory variation in arterial pulse
      pressure and respiratory variation in POP waveform amplitude were recorded
      simultaneously in a beat-to-beat evaluation, and were compared using a Spearman
      correlation test and a Bland-Altman analysis. RESULTS: There was a strong
      correlation (r2 = 0.83; P < 0.001) and a good agreement (bias = 0.8 +/- 3.5%)
      between respiratory variation in arterial pulse pressure and respiratory
      variation in POP waveform amplitude. A respiratory variation in POP waveform
      amplitude value above 15% allowed discrimination between patients with
      respiratory variation in arterial pulse pressure above 13% and those with
      variation of 13% or less (positive predictive value 100%). CONCLUSION:
      Respiratory variation in arterial pulse pressure above 13% can be accurately
      predicted by a respiratory variation in POP waveform amplitude above 15%. This
      index has potential applications in patients who are not instrumented with an
      intra-arterial catheter.

PMID- 16277720
TI  - Effects of reduced rebreathing time, in spontaneously breathing patients, on
      respiratory effort and accuracy in cardiac output measurement when using a
      partial carbon dioxide rebreathing technique: a prospective observational study.
AB  - INTRODUCTION: New technology using partial carbon dioxide rebreathing has been
      developed to measure cardiac output. Because rebreathing increases respiratory
      effort, we investigated whether a newly developed system with 35 s rebreathing
      causes a lesser increase in respiratory effort under partial ventilatory support
      than does the conventional system with 50 s rebreathing. We also investigated
      whether the shorter rebreathing period affects the accuracy of cardiac output
      measurement. METHOD: Once a total of 13 consecutive post-cardiac-surgery patients
      had recovered spontaneous breathing under pressure support ventilation, we
      applied a partial carbon dioxide rebreathing technique with rebreathing of 35 s
      and 50 s in a random order. We measured minute ventilation, and arterial and
      mixed venous carbon dioxide tension at the end of the normal breathing period and
      at the end of the rebreathing periods. We then measured cardiac output using the
      partial carbon dioxide rebreathing technique with the two rebreathing periods and
      using thermodilution. RESULTS: With both rebreathing systems, minute ventilation
      increased during rebreathing, as did arterial and mixed venous carbon dioxide
      tensions. The increases in minute ventilation and arterial carbon dioxide tension
      were less with 35 s rebreathing than with 50 s rebreathing. The cardiac output
      measures with both systems correlated acceptably with values obtained with
      thermodilution. CONCLUSION: When patients breathe spontaneously the partial
      carbon dioxide rebreathing technique increases minute ventilation and arterial
      carbon dioxide tension, but the effect is less with a shorter rebreathing period.
      The 35 s rebreathing period yielded cardiac output measurements similar in
      accuracy to those with 50 s rebreathing.

PMID- 16277721
TI  - A systematic evaluation of the quality of meta-analyses in the critical care
      literature.
AB  - INTRODUCTION: Meta-analyses have been suggested to be the highest form of
      evidence available to clinicians to guide clinical practice in critical care. The
      purpose of this study was to systematically evaluate the quality of meta-analyses
      that address topics pertinent to critical care. METHODS: To identify potentially
      eligible meta-analyses for inclusion, a systematic search of Medline, EMBASE and
      the Cochrane Database of Systematic Reviews was undertaken, using broad search
      terms relevant to intensive care, including: intensive care, critical care,
      shock, resuscitation, inotropes and mechanical ventilation. Predetermined
      inclusion criteria were applied to each identified meta-analysis independently by
      two authors. To assess report quality, the included meta-analyses were assessed
      using the component and overall scores from the Overview Quality Assessment
      Questionnaire (OQAQ). The quality of reports published before and after the
      publication of the QUOROM statement was compared. RESULTS: A total of 139 reports
      of meta-analyses were included (kappa = 0.93). The overall quality of reports of
      meta-analyses was found to be poor, with an estimated mean overall OQAQ score of
      3.3 (95% CI; 3.0-3.6). Only 43 (30.9%) were scored as having minimal or minor
      flaws (>5). We noted problems with the reporting of key characteristics of meta
      analyses, such as performing a thorough literature search, avoidance of bias in
      the inclusion of studies and appropriately referring to the validity of the
      included studies. After the release of the QUOROM statement, however, an
      improvement in the overall quality of published meta-analyses was noted.
      CONCLUSION: The overall quality of the reports of meta-analyses available to
      critical care physicians is poor. Physicians should critically evaluate these
      studies prior to considering applying the results of these studies in their
      clinical practice.

PMID- 16277722
TI  - Hospital-acquired sinusitis is a common cause of fever of unknown origin in
      orotracheally intubated critically ill patients.
AB  - INTRODUCTION: Sinusitis is a well recognised but insufficiently understood
      complication of critical illness. It has been linked to nasotracheal intubation,
      but its occurrence after orotracheal intubation is less clear. We studied the
      incidence of sinusitis in patients with fever of unknown origin (FUO) in our
      intensive care unit with the aim of establishing a protocol that would be
      applicable in everyday clinical practice. METHODS: Sinus X-rays (SXRs) were
      performed in all patients with fever for which an initial screening (physical
      examination, microbiological cultures and chest X-ray) revealed no obvious cause.
      All patients were followed with a predefined protocol, including antral drainage
      in all patients with abnormal or equivocal results on their SXR. RESULTS: Initial
      screening revealed probable causes of fever in 153 of 351 patients (43.6%). SXRs
      were taken in the other 198 patients (56.4%); 129 had obvious or equivocal
      abnormalities. Sinus drainage revealed purulent material and positive cultures
      (predominantly Pseudomonas and Klebsiella species) in 84 patients. Final
      diagnosis for the cause of fever in all 351 patients based on X-ray results,
      microbiological cultures, and clinical response to sinus drainage indicated
      sinusitis as the sole cause of fever in 57 (16.2%) and as contributing factor in
      48 (13.8%) patients with FUO. This will underestimate the actual incidence
      because SXR and drainage were not performed in all patients. CONCLUSION:
      Physicians treating critically ill patients should be aware of the high risk of
      sinusitis and take appropriate preventive measures, including the removal of
      nasogastric tubes in patients requiring long-term mechanical ventilation. Routine
      investigation of FUO should include computed tomography scan, SXR or sinus
      ultrasonography, and drainage should be performed if any abnormalities are found.

PMID- 16277723
TI  - Circulating anions usually associated with the Krebs cycle in patients with
      metabolic acidosis.
AB  - INTRODUCTION: Acute metabolic acidosis of non-renal origin is usually a result of
      either lactic or ketoacidosis, both of which are associated with a high anion
      gap. There is increasing recognition, however, of a group of acidotic patients
      who have a large anion gap that is not explained by either keto- or lactic
      acidosis nor, in most cases, is inappropriate fluid resuscitation or ingestion of
      exogenous agents the cause. METHODS: Plasma ultrafiltrate from patients with
      diabetic ketoacidosis, lactic acidosis, acidosis of unknown cause, normal anion
      gap metabolic acidosis, or acidosis as a result of base loss were examined
      enzymatically for the presence of low molecular weight anions including citrate,
      isocitrate, alpha-ketoglutarate, succinate, malate and d-lactate. The results
      obtained from the study groups were compared with those obtained from control
      plasma from normal volunteers. RESULTS: In five patients with lactic acidosis, a
      significant increase in isocitrate (0.71 +/- 0.35 mEq l-1), alpha-ketoglutarate
      (0.55 +/- 0.35 mEq l-1), malate (0.59 +/- 0.27 mEq l-1), and d-lactate (0.40 +/-
      0.51 mEq l-1) was observed. In 13 patients with diabetic ketoacidosis,
      significant increases in isocitrate (0.42 +/- 0.35 mEq l-1), alpha-ketoglutarate
      (0.41 +/- 0.16 mEq l-1), malate (0.23 +/- 0.18 mEq l-1) and d-lactate (0.16 +/-
      0.07 mEq l-1) were seen. Neither citrate nor succinate levels were increased.
      Similar findings were also observed in a further five patients with high anion
      gap acidosis of unknown origin with increases in isocitrate (0.95 +/- 0.88 mEq l
      1), alpha-ketoglutarate (0.65 +/- 0.20 mEq l-1), succinate (0.34 +/- 0.13 mEq l
      1), malate (0.49 +/- 0.19 mEq l-1) and d-lactate (0.18 +/- 0.14 mEq l-1) being
      observed but not in citrate concentration. In five patients with a normal anion
      gap acidosis, no increases were observed except a modest rise in d-lactate (0.17
      +/- 0.14 mEq l-1). CONCLUSION: The levels of certain low molecular weight anions
      usually associated with intermediary metabolism were found to be significantly
      elevated in the plasma ultrafiltrate obtained from patients with metabolic
      acidosis. Our results suggest that these hitherto unmeasured anions may
      significantly contribute to the generation of the anion gap in patients with
      lactic acidosis and acidosis of unknown aetiology and may be underestimated in
      diabetic ketoacidosis. These anions are not significantly elevated in patients
      with normal anion gap acidosis.

PMID- 16277724
TI  - Recently published papers: what not to do and how not to do it?
AB  - Controversies abound in the areas of blood transfusion, albumin, lipoproteins in
      sepsis and pulmonary artery catheters. We are also making too many errors, but at
      least there is a new nitric oxide therapy in the offing.

PMID- 16277725
TI  - The role of leadership in overcoming staff turnover in critical care.
AB  - This commentary discusses Laporta and coworkers analysis of a case study on the
      causes of and solutions for staff turnover in an intensive care setting. Staff
      turnover is a significant issue for health care leaders due to the shrinking
      workforce in Western countries and an increased demand for intensive care
      services as the population ages. The commentary considers reasons for turnover
      such as burnout and generational diversity, and highlights the importance of a
      team work approach to address the issue of turnover.

PMID- 16277726
TI  - Recruitment maneuvers and positive end-expiratory pressure/tidal ventilation
      titration in acute lung injury/acute respiratory distress syndrome: translating
      experimental results to clinical practice.
AB  - Recruitment maneuvers and positive end-expiratory pressure (PEEP)/tidal
      ventilation titration in acute lung injury/acute respiratory distress syndrome
      (ALI/ARDS) are the cornerstone of mechanical ventilatory support. The net result
      of these possible adjustments in ventilatory parameters is the interaction of the
      pressure applied in the respiratory system (airway pressure/end expiratory
      pressure) counterbalanced by chest wall configuration/abdominal pressure along
      the mechanical ventilatory support duration. Refinements in the ventilatory
      adjustments in ALI/ARDS are necessary for minimizing the biotrauma in this still
      life-threatening clinical problem.

PMID- 16277728
TI  - What do we know about medication errors made via a CPOE system versus those made
      via handwritten orders?
AB  - This commentary on the article by Shulman et al. examines what we understand by
      'medication errors', what we mean by 'computerized physician order entry (CPOE)
      systems', how we measure errors, and what types of errors we are 'reducing' with
      CPOE systems. As the research of Shulman and colleagues highlights, much of the
      existing research on CPOE systems does not differentiate among: types of
      medication errors; consequential versus inconsequential medication errors; CPOE
      systems that include/exclude formal decision support packages; and the extent to
      which decision support information is implicitly presented to physicians via the
      CPOE system, for example, pull down menus with dosages. I discuss these issues
      and their implications for the evaluation of CPOE systems and of other emerging
      healthcare technologies.

PMID- 16277729
TI  - Pulse oximeter as a sensor of fluid responsiveness: do we have our finger on the
      best solution?
AB  - The pulse oximetry plethysmographic signal resembles the peripheral arterial
      pressure waveform, and the degree of respiratory variation in the pulse oximetry
      wave is close to the degree of respiratory arterial pulse pressure variation.
      Thus, it is tempting to speculate that pulse oximetry can be used to assess
      preload responsiveness in mechanically ventilated patients. In this commentary we
      briefly review the complex meaning of the pulse oximetry plethysmographic signal
      and highlight the advantages, limitations and pitfalls of the pulse oximetry
      method. Future studies including volume challenge must be performed to test
      whether the pulse oximetry waveform can really serve as a nonivasive tool for the
      guidance of fluid therapy in patients receiving mechanical ventilation in
      intensive care units and in operating rooms.

PMID- 16277730
TI  - Science review: carnitine in the treatment of valproic acid-induced toxicity -
      what is the evidence?
AB  - Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well
      tolerated, but rare serious complications may occur in some patients receiving
      VPA chronically, including haemorrhagic pancreatitis, bone marrow suppression,
      VPA-induced hepatotoxicity (VHT) and VPA-induced hyperammonaemic encephalopathy
      (VHE). Some data suggest that VHT and VHE may be promoted by carnitine
      deficiency. Acute VPA intoxication also occurs as a consequence of intentional or
      accidental overdose and its incidence is increasing, because of use of VPA in
      psychiatric disorders. Although it usually results in mild central nervous system
      depression, serious toxicity and even fatal cases have been reported. Several
      studies or isolated clinical observations have suggested the potential value of
      oral L-carnitine in reversing carnitine deficiency or preventing its development
      as well as some adverse effects due to VPA. Carnitine supplementation during VPA
      therapy in high-risk patients is now recommended by some scientific committees
      and textbooks, especially paediatricians. L-carnitine therapy could also be
      valuable in those patients who develop VHT or VHE. A few isolated observations
      also suggest that L-carnitine may be useful in patients with coma or in
      preventing hepatic dysfunction after acute VPA overdose. However, these issues
      deserve further investigation in controlled, randomized and probably multicentre
      trials to evaluate the clinical value and the appropriate dosage of L-carnitine
      in each of these conditions.

PMID- 16277731
TI  - Bench-to-bedside review: oxygen debt and its metabolic correlates as quantifiers
      of the severity of hemorrhagic and post-traumatic shock.
AB  - Evidence is increasing that oxygen debt and its metabolic correlates are
      important quantifiers of the severity of hemorrhagic and post-traumatic shock and
      and may serve as useful guides in the treatment of these conditions. The aim of
      this review is to demonstrate the similarity between experimental oxygen debt in
      animals and human hemorrhage/post-traumatic conditions, and to examine metabolic
      oxygen debt correlates, namely base deficit and lactate, as indices of shock
      severity and adequacy of volume resuscitation. Relevant studies in the medical
      literature were identified using Medline and Cochrane Library searches. Findings
      in both experimental animals (dog/pig) and humans suggest that oxygen debt or its
      metabolic correlates may be more useful quantifiers of hemorrhagic shock than
      estimates of blood loss, volume replacement, blood pressure, or heart rate. This
      is evidenced by the oxygen debt/probability of death curves for the animals, and
      by the consistency of lethal dose (LD)25,50 points for base deficit across all
      three species. Quantifying human post-traumatic shock based on base deficit and
      adjusting for Glasgow Coma Scale score, prothrombin time, Injury Severity Score
      and age is demonstrated to be superior to anatomic injury severity alone or in
      combination with Trauma and Injury Severity Score. The data examined in this
      review indicate that estimates of oxygen debt and its metabolic correlates should
      be included in studies of experimental shock and in the management of patients
      suffering from hemorrhagic shock.

PMID- 16277732
TI  - Bench-to-bedside review: dealing with increased intensive care unit staff
      turnover: a leadership challenge.
AB  - Critical care leaders frequently must face challenging situations requiring
      specific leadership and management skills for which they are, not uncommonly,
      poorly prepared. Such a fictitious scenario was discussed at a Canadian
      interdisciplinary critical care leadership meeting, whereby increasing intensive
      care unit (ICU) staff turnover had led to problems with staff recruitment.
      Participants discussed and proposed solutions to the scenario in a structured
      format. The results of the discussion are presented. In situations such as this,
      the ICU leader should first define the core problem, its complexity, its duration
      and its potential for reversibility. These factors often reside within workload
      and staff support issues. Some examples of core problems discussed that are
      frequently associated with poor retention and recruitment are a lack of a
      positive team culture, a lack of a favorable ICU image, a lack of good working
      relationships between staff and disciplines, and a lack of specific supportive
      resources. Several tools or individuals (typically outside the ICU environment)
      are available to help determine the core problem. Once the core problem is
      identified, specific solutions can be developed. Such solutions often require
      originality and flexibility, and must be planned, with specific short-term,
      medium-term and long-term goals. The ICU leader will need to develop an
      implementation strategy for these solutions, in which partners who can assist are
      identified from within the ICU and from outside the ICU. It is important that the
      leader communicates to all stakeholders frequently as the process moves forward.

PMID- 16277734
TI  - Bench-to-bedside review: antimicrobial utilization strategies aimed at preventing
      the emergence of bacterial resistance in the intensive care unit.
AB  - Antimicrobial resistance has emerged as one of the most important issues
      complicating the management of critically ill patients with infection. This is
      largely due to the increasing presence of pathogenic microorganisms with
      resistance to existing antimicrobial agents resulting in the administration of
      inappropriate treatment. Effective strategies for the prevention of antimicrobial
      resistance within intensive care units are available and should be aggressively
      implemented. The importance of preventing antimicrobial resistance is magnified
      by the limited availability of new antimicrobial drug classes for the foreseeable
      future.

PMID- 16277735
TI  - Bench-to-bedside review: adjuncts to mechanical ventilation in patients with
      acute lung injury.
AB  - Mechanical ventilation is indispensable for the survival of patients with acute
      lung injury and acute respiratory distress syndrome. However, excessive tidal
      volumes and inadequate lung recruitment may contribute to mortality by causing
      ventilator-induced lung injury. This bench-to-bedside review presents the
      scientific rationale for using adjuncts to mechanical ventilation aimed at
      optimizing lung recruitment and preventing the deleterious consequences of
      reduced tidal volume. To enhance CO2 elimination when tidal volume is reduced,
      the following are possible: first, ventilator respiratory frequency can be
      increased without necessarily generating intrinsic positive end-expiratory
      pressure; second, instrumental dead space can be reduced by replacing the heat
      and moisture exchanger with a conventional humidifier; and third, expiratory
      washout can be used for replacing the CO2-laden gas present at end expiration in
      the instrumental dead space by a fresh gas (this method is still experimental).
      For optimizing lung recruitment and preventing lung derecruitment there are the
      following possibilities: first, recruitment manoeuvres may be performed in the
      most hypoxaemic patients before implementing the preset positive end-expiratory
      pressure or after episodes of accidental lung derecruitment; second, the patient
      can be turned to the prone position; third, closed-circuit endotracheal
      suctioning is to be preferred to open endotracheal suctioning.

PMID- 16277736
TI  - Clinical review: respiratory mechanics in spontaneous and assisted ventilation.
AB  - Pulmonary disease changes the physiology of the lungs, which manifests as changes
      in respiratory mechanics. Therefore, measurement of respiratory mechanics allows
      a clinician to monitor closely the course of pulmonary disease. Here we review
      the principles of respiratory mechanics and their clinical applications. These
      principles include compliance, elastance, resistance, impedance, flow, and work
      of breathing. We discuss these principles in normal conditions and in disease
      states. As the severity of pulmonary disease increases, mechanical ventilation
      can become necessary. We discuss the use of pressure-volume curves in assisting
      with poorly compliant lungs while on mechanical ventilation. In addition, we
      discuss physiologic parameters that assist with ventilator weaning as the disease
      process abates.

PMID- 16277737
TI  - Clinical review: role of triggering receptor expressed on myeloid cells-1 during
      sepsis.
AB  - Triggering receptor expressed on myeloid cells (TREM)-1 is a recently identified
      molecule that is involved in monocytic activation and in the inflammatory
      response. It belongs to a family related to the natural killer cell receptors and
      is expressed on neutrophils, mature monocytes and macrophages. The inflammatory
      response mediated by Toll-like receptor-2 and -4 stimulation is amplified by the
      engagement of TREM-1. The expression of membrane-bound TREM-1 is greatly
      increased on monocytes during sepsis. Moreover, infection induces the release of
      a soluble form of this receptor, which can be measured in biological fluid and
      may be useful as a diagnostic tool. Modulation of the TREM-1 signalling pathway
      by the use of small synthetic peptides confers interesting survival advantages
      during experimental septic shock in mice, even when this teatment is administered
      late after the onset of sepsis.

PMID- 16277738
TI  - Clinical review: the Israeli experience: conventional terrorism and critical
      care.
AB  - Over the past four years there have been 93 multiple-casualty terrorist attacks
      in Israel, 33 of them in Jerusalem. The Hadassah-Hebrew University Medical Center
      is the only Level I trauma center in Jerusalem and has therefore gained important
      experience in caring for critically injured patients. To do so we have developed
      a highly flexible operational system for managing the general intensive care unit
      (GICU). The focus of this review will be on the organizational steps needed to
      provide operational flexibility, emphasizing the importance of forward deployment
      of intensive care unit personnel to the trauma bay and emergency room and the
      existence of a chain of command to limit chaos. A retrospective review of the
      hospital's response to multiple-casualty terror incidents occurring between 1
      October 2000 and 1 September 2004 was performed. Information was assembled from
      the medical center's trauma registry and from GICU patient admission and
      discharge records. Patients are described with regard to the severity and type of
      injury. The organizational work within intensive care is described. Finally,
      specific issues related to the diagnosis and management of lung, brain,
      orthopedic and abdominal injuries, caused by bomb blast events associated with
      shrapnel, are described. This review emphasizes the importance of a
      multidisciplinary team approach in caring for these patients.

PMID- 16277739
TI  - Clinical review: reunification of acid-base physiology.
AB  - Recent advances in acid-base physiology and in the epidemiology of acid-base
      disorders have refined our understanding of the basic control mechanisms that
      determine blood pH in health and disease. These refinements have also brought
      parity between the newer, quantitative and older, descriptive approaches to acid
      base physiology. This review explores how the new and older approaches to acid
      base physiology can be reconciled and combined to result in a powerful bedside
      tool. A case based tutorial is also provided.

PMID- 16277740
TI  - Clinical review: the meaning of acid-base abnormalities in the intensive care
      unit part I - epidemiology.
AB  - Acid-base abnormalities are common in critically ill patients. Our ability to
      describe acid-base disorders must be precise. Small differences in corrections
      for anion gap, different types of analytical processes, and the basic approach
      used to diagnose acid-base aberrations can lead to markedly different
      interpretations and treatment strategies for the same disorder. By applying a
      quantitive acid-base approach, clinicians are able to account for small changes
      in ion distribution that may have gone unrecognized with traditional techniques
      of acid-base analysis. Outcome prediction based on the quantitative approach
      remains controversial. This is in part due to use of various technologies to
      measure acid-base variables, administration of fluid or medication that can alter
      acid-base results, and lack of standardized nomenclature. Without controlling for
      these factors it is difficult to appreciate the full effect that acid-base
      disorders have on patient outcomes, ultimately making results of outcome studies
      hard to compare.

PMID- 16277741
TI  - Year in review in Critical Care, 2003 and 2004: respirology and critical care.
AB  - We summarize all original research in the field of respirology and critical care
      published in 2003 and 2004 in Critical Care. Articles were grouped into the
      following categories to facilitate a rapid overview: pathophysiology, therapeutic
      approaches, and outcome in acute lung injury and acute respiratory distress
      syndrome; hypoxic pulmonary arterial hypertension; mechanical ventilation;
      liberation from mechanical ventilation and tracheostomy; ventilator-associated
      pneumonia; multidrug-resistant infections; pleural effusion; sedation and
      analgesia; asthma; and techniques and monitoring.

PMID- 16277742
TI  - Year in review: Critical Care 2004 - nephrology.
AB  - We summarize all original research in the field of critical care nephrology
      published in 2004 or accepted for publication in Critical Care and, when
      considered relevant or directly linked to this research, in other journals.
      Articles were grouped into four categories to facilitate a rapid overview. First,
      regarding the definition of acute renal failure (ARF), the RIFLE criteria (risk,
      injury, failure, loss, ESKD [end-stage kidney disease]) for diagnosis of ARF were
      defined by the Acute Dialysis Quality Initiative workgroup and applied in
      clinical practice by some authors. The second category is acid-base disorders in
      ARF; the Stewart-Figge quantitative approach to acidosis in critically ill
      patients has been utilized by two groups of researchers, with similar results but
      different conclusions. In the third category - blood markers during ARF -
      cystatin C as an early marker of ARF and procalcitonin as a sepsis marker during
      continuous venovenous haemofiltration were examined. Finally, in the
      extracorporeal treatment of ARF, the ability of two types of high cutoff
      haemofilters to influence blood levels of middle- and high-molecular-weight
      toxins showed promise.

PMID- 16277743
TI  - Effect of intern's consecutive work hours on safety, medical education and
      professionalism.

PMID- 16277744
TI  - Cystatin C: unsuited to use as a marker of kidney function in the intensive care
      unit.
AB  - : We read with interest the article by Villa and coworkers 1 advocating the use
      of cystatin C as a measure of glomerular filtration rate (GFR) in critically ill
      patients. However, we should like to draw attention to several flaws in this
      study. First, Villa and coworkers compared cystatin C with creatinine as a
      measure of GFR, using body surface corrected creatinine clearance as, what they
      call, a 'gold standard'. However, in the Discussion section of that report inulin
      and iothalamate clearances are mentioned as gold standards, but they were not
      used by these investigators. The use of body surface area corrected creatinine
      clearance is questionable in both obese and excessively lean individuals because
      the correlation between surface area and lean body mass may be lost. Both types
      of patients are frequently encountered in intensive care. Second, Villa and
      coworkers employ a cutoff of 80 ml/min to identify renal dysfunction, whereas a
      value of 50 ml/min is generally accepted 2. This could have a major influence on
      the presented results. Third, patients with thyroid disorders or on
      corticosteroid therapy were excluded. Almost all patients with critical illness
      have low tri-iodothyronine values because of changes in thyroid hormone
      metabolism ('nonthyroidal illness'), thus making recognition of thyroid disorders
      problematic. Finally, we showed 3 that, in patients with thyroid dysfunction,
      cystatin C is not a suitable measure of GFR. In hypothyroidism creatinine levels
      are elevated but cystatin C levels are low, whereas in hyperthyroidism creatinine
      levels are low and cystatin C levels elevated. Taken together, we disagree with
      the authors that cystatin C could be used as a marker of GFR in intensive care
      patients.

PMID- 16277745
TI  - Chromatin and siRNA pathways cooperate to maintain DNA methylation of small
      transposable elements in Arabidopsis.
AB  - BACKGROUND: DNA methylation occurs at preferred sites in eukaryotes. In
      Arabidopsis, DNA cytosine methylation is maintained by three subfamilies of
      methyltransferases with distinct substrate specificities and different modes of
      action. Targeting of cytosine methylation at selected loci has been found to
      sometimes involve histone H3 methylation and small interfering (si)RNAs. However,
      the relationship between different cytosine methylation pathways and their
      preferred targets is not known. RESULTS: We used a microarray-based profiling
      method to explore the involvement of Arabidopsis CMT3 and DRM DNA
      methyltransferases, a histone H3 lysine-9 methyltransferase (KYP) and an
      Argonaute-related siRNA silencing component (AGO4) in methylating target loci. We
      found that KYP targets are also CMT3 targets, suggesting that histone methylation
      maintains CNG methylation genome-wide. CMT3 and KYP targets show similar proximal
      distributions that correspond to the overall distribution of transposable
      elements of all types, whereas DRM targets are distributed more distally along
      the chromosome. We find an inverse relationship between element size and loss of
      methylation in ago4 and drm mutants. CONCLUSION: We conclude that the targets of
      both DNA methylation and histone H3K9 methylation pathways are transposable
      elements genome-wide, irrespective of element type and position. Our findings
      also suggest that RNA-directed DNA methylation is required to silence isolated
      elements that may be too small to be maintained in a silent state by a chromatin
      based mechanism alone. Thus, parallel pathways would be needed to maintain
      silencing of transposable elements.

PMID- 16277746
TI  - Do universal codon-usage patterns minimize the effects of mutation and
      translation error?
AB  - BACKGROUND: Do species use codons that reduce the impact of errors in translation
      or replication? The genetic code is arranged in a way that minimizes errors,
      defined as the sum of the differences in amino-acid properties caused by single
      base changes from each codon to each other codon. However, the extent to which
      organisms optimize the genetic messages written in this code has been far less
      studied. We tested whether codon and amino-acid usages from 457 bacteria, 264
      eukaryotes, and 33 archaea minimize errors compared to random usages, and whether
      changes in genome G+C content influence these error values. RESULTS: We tested
      the hypotheses that organisms choose their codon usage to minimize errors, and
      that the large observed variation in G+C content in coding sequences, but the low
      variation in G+U or G+A content, is due to differences in the effects of
      variation along these axes on the error value. Surprisingly, the biological
      distribution of error values has far lower variance than randomized error values,
      but error values of actual codon and amino-acid usages are actually greater than
      would be expected by chance. CONCLUSION: These unexpected findings suggest that
      selection against translation error has not produced codon or amino-acid usages
      that minimize the effects of errors, and that even messages with very different
      nucleotide compositions somehow maintain a relatively constant error value. They
      raise the question: why do all known organisms use highly error-minimizing
      genetic codes, but fail to minimize the errors in the mRNA messages they encode?

PMID- 16277747
TI  - The interferon-inducible p47 (IRG) GTPases in vertebrates: loss of the cell
      autonomous resistance mechanism in the human lineage.
AB  - BACKGROUND: Members of the p47 (immunity-related GTPases (IRG) family) GTPases
      are essential, interferon-inducible resistance factors in mice that are active
      against a broad spectrum of important intracellular pathogens. Surprisingly,
      there are no reports of p47 function in humans. RESULTS: Here we show that the
      p47 GTPases are represented by 23 genes in the mouse, whereas humans have only a
      single full-length p47 GTPase and an expressed, truncated presumed pseudo-gene.
      The human full-length gene is orthologous to an isolated mouse p47 GTPase that
      carries no interferon-inducible elements in the promoter of either species and is
      expressed constitutively in the mature testis of both species. Thus, there is no
      evidence for a p47 GTPase-based resistance system in humans. Dogs have several
      interferon-inducible p47s, and so the primate lineage that led to humans appears
      to have lost an ancient function. Multiple p47 GTPases are also present in the
      zebrafish, but there is only a tandem p47 gene pair in pufferfish. CONCLUSION:
      Mice and humans must deploy their immune resources against vacuolar pathogens in
      radically different ways. This carries significant implications for the use of
      the mouse as a model of human infectious disease. The absence of the p47
      resistance system in humans suggests that possession of this resistance system
      carries significant costs that, in the primate lineage that led to humans, are
      not outweighed by the benefits. The origin of the vertebrate p47 system is
      obscure.

PMID- 16277748
TI  - Transcriptome analysis of antigenic variation in Plasmodium falciparum--var
      silencing is not dependent on antisense RNA.
AB  - BACKGROUND: Plasmodium falciparum, the causative agent of the most severe form of
      malaria, undergoes antigenic variation through successive presentation of a
      family of antigens on the surface of parasitized erythrocytes. These antigens,
      known as Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins,
      are subject to a mutually exclusive expression system, and are encoded by the
      multigene var family. The mechanism whereby inactive var genes are silenced is
      poorly understood. To investigate transcriptional features of this mechanism, we
      conducted a microarray analysis of parasites that were selected to express
      different var genes by adhesion to chondroitin sulfate A (CSA) or CD36. RESULTS:
      In addition to oligonucleotides for all predicted protein-coding genes,
      oligonucleotide probes specific to each known var gene of the FCR3 background
      were designed and added to the microarray, as well as tiled sense and antisense
      probes for a subset of var genes. In parasites selected for adhesion to CSA, one
      full-length var gene (var2csa) was strongly upregulated, as were sense RNA
      molecules emanating from the 3' end of a limited subset of other var genes. No
      global relationship between sense and antisense production of var genes was
      observed, but notably, some var genes had coincident high levels of both
      antisense and sense transcript. CONCLUSION: Mutually exclusive expression of
      PfEMP1 proteins results from transcriptional silencing of non-expressed var
      genes. The distribution of steady-state sense and antisense RNA at var loci are
      not consistent with a silencing mechanism based on antisense silencing of
      inactive var genes. Silencing of var loci is also associated with altered
      regulation of genes distal to var loci.

PMID- 16277749
TI  - Genome-wide gene expression in response to parasitoid attack in Drosophila.
AB  - BACKGROUND: Parasitoids are insect parasites whose larvae develop in the bodies
      of other insects. The main immune defense against parasitoids is encapsulation of
      the foreign body by blood cells, which subsequently often melanize. The capsule
      sequesters and kills the parasite. The molecular processes involved are still
      poorly understood, especially compared with insect humoral immunity. RESULTS: We
      explored the transcriptional response to parasitoid attack in Drosophila larvae
      at nine time points following parasitism, hybridizing five biologic replicates
      per time point to whole-genome microarrays for both parasitized and control
      larvae. We found significantly different expression profiles for 159 probe sets
      (representing genes), and we classified them into 16 clusters based on patterns
      of co-expression. A series of functional annotations were nonrandomly associated
      with different clusters, including several involving immunity and related
      functions. We also identified nonrandom associations of transcription factor
      binding sites for three main regulators of innate immune responses (GATA/srp
      like, NF-kappaB/Rel-like and Stat), as well as a novel putative binding site for
      an unknown transcription factor. The appearance or absence of candidate genes
      previously associated with insect immunity in our differentially expressed gene
      set was surveyed. CONCLUSION: Most genes that exhibited altered expression
      following parasitoid attack differed from those induced during antimicrobial
      immune responses, and had not previously been associated with defense. Applying
      bioinformatic techniques contributed toward a description of the encapsulation
      response as an integrated system, identifying putative regulators of co-expressed
      and functionally related genes. Genome-wide studies such as ours are a powerful
      first approach to investigating novel genes involved in invertebrate immunity.

PMID- 16277750
TI  - A computational investigation of kinetoplastid trans-splicing.
AB  - Trans-splicing is an unusual process in which two separate RNA strands are
      spliced together to yield a mature mRNA. We present a novel computational
      approach which has an overall accuracy of 82% and can predict 92% of known trans
      splicing sites. We have applied our method to chromosomes 1 and 3 of Leishmania
      major, with high-confidence predictions for 85% and 88% of annotated genes
      respectively. We suggest some extensions of our method to other systems.

PMID- 16277751
TI  - Chipper: discovering transcription-factor targets from chromatin
      immunoprecipitation microarrays using variance stabilization.
AB  - Chromatin immunoprecipitation combined with microarray technology (Chip2) allows
      genome-wide determination of protein-DNA binding sites. The current standard
      method for analyzing Chip2 data requires additional control experiments that are
      subject to systematic error. We developed methods to assess significance using
      variance stabilization, learning error-model parameters without external control
      experiments. The method was validated experimentally, shows greater sensitivity
      than the current standard method, and incorporates false-discovery rate analysis.
      The corresponding software ('Chipper') is freely available. The method described
      here should help reveal an organism's transcription-regulatory 'wiring diagram'.

PMID- 16277752
TI  - ChIPOTle: a user-friendly tool for the analysis of ChIP-chip data.
AB  - ChIPOTle (Chromatin ImmunoPrecipitation On Tiled arrays) takes advantage of two
      unique properties of ChIP-chip data: the single-tailed nature of the data, caused
      by specific enrichment but not specific depletion of genomic fragments; and the
      predictable enrichment of DNA fragments adjacent to sites of direct protein-DNA
      interaction. Implemented as a Microsoft Excel macro written in Visual Basic,
      ChIPOTle uses a sliding window approach that yields improvements in the
      identification of bona fide sites of protein-DNA interaction.

PMID- 16277753
TI  - H5N1.

PMID- 16277754
TI  - Large-scale approaches for glycobiology.
AB  - Glycosylation, the attachment of carbohydrates to proteins and lipids, influences
      many biological processes. Despite detailed characterization of the cellular
      components that carry out glycosylation, a complete picture of a cell's
      glycoconjugates remains elusive because of the challenges inherent in
      characterizing complex carbohydrates. This article reviews large-scale techniques
      for accelerating progress in glycobiology.

PMID- 16277755
TI  - Close encounters between active genes in the nucleus.
AB  - A recent paper demonstrates that coregulated genes on different chromosomes show
      surprisingly high frequencies of colocalization within the nucleus; this
      complements similar results found previously for genes localized tens of
      megabases apart on a single chromosome. Colocalization could be related to the
      earlier observation of active genes associating with foci where RNA polymerase II
      is concentrated.

PMID- 16277756
TI  - Virus-host interactions: new insights from the small RNA world.
AB  - RNA silencing has a known role in the antiviral responses of plants and insects.
      Recent evidence, including the finding that the Tat protein of human
      immunodeficiency virus (HIV) can suppress the host's RNA-silencing pathway and
      may thus counteract host antiviral RNAs, suggests that RNA-silencing pathways
      could also have key roles in mammalian virus-host interactions.

PMID- 16277757
TI  - Metabolomics shows the way to new discoveries.

PMID- 16277758
TI  - Chromatin dynamics rule the genome.

PMID- 16277759
TI  - Caenorhabditis elegans and friends in Los Angeles.

PMID- 16277760
TI  - Utilization of essential amino acids synthesized in the intestinal microbiota of
      monogastric mammals.

PMID- 16277761
TI  - The case for strategic international alliances to harness nutritional genomics
      for public and personal health.
AB  - Nutrigenomics is the study of how constituents of the diet interact with genes,
      and their products, to alter phenotype and, conversely, how genes and their
      products metabolise these constituents into nutrients, antinutrients, and
      bioactive compounds. Results from molecular and genetic epidemiological studies
      indicate that dietary unbalance can alter gene-nutrient interactions in ways that
      increase the risk of developing chronic disease. The interplay of human genetic
      variation and environmental factors will make identifying causative genes and
      nutrients a formidable, but not intractable, challenge. We provide specific
      recommendations for how to best meet this challenge and discuss the need for new
      methodologies and the use of comprehensive analyses of nutrient-genotype
      interactions involving large and diverse populations. The objective of the
      present paper is to stimulate discourse and collaboration among nutrigenomic
      researchers and stakeholders, a process that will lead to an increase in global
      health and wellness by reducing health disparities in developed and developing
      countries.

PMID- 16277762
TI  - A review of the instruments used to assess the quality of life of adult patients
      with chronic intestinal failure receiving parenteral nutrition at home.
AB  - Home parenteral nutrition is an established method of supporting patients with
      intestinal failure, but this treatment may be life long and imposes severe
      restrictions on daily life. Impact on quality of life is an important outcome
      when considering the management of home parenteral nutrition patients. This paper
      reviews studies in which the quality of life of patients receiving home
      parenteral nutrition has been assessed. A systematic search of electronic
      databases and relevant publications was undertaken to identify generic or
      treatment-specific questionnaires used with home parenteral nutrition patients.
      Many of the thirty-four reports discovered were small studies. Nineteen used non
      specific generic instruments, eight used non-validated questionnaires, four used
      a combination of both, and three did not use any formal tool. Few systematic
      patterns emerged. There are few available data on the quality of life of home
      parenteral nutrition patients, and there is a need for standardised,
      scientifically validated, treatment-specific instruments to measure quality of
      life in this population.

PMID- 16277763
TI  - Dietary habits are major determinants of the plasma antioxidant status in healthy
      elderly subjects.
AB  - Previous studies indicate that regular consumption of a diet rich in fruits and
      vegetables is associated with a lower risk for age-related diseases. The aim of
      the present study was to evaluate whether the often-reported age-related decrease
      of plasma antioxidants in man depends on differences in dietary intake or on
      other age- and gender-related factors. In this observational case-control study,
      thirty-nine community-dwelling healthy subjects aged 65 years and older consuming
      high intakes of fruits and vegetables daily (HI) and forty-eight healthy subjects
      aged 65 and older consuming low intakes of fruit and vegetables daily (LI) were
      enrolled. Plasma levels of retinol, tocopherols, carotenoids and malondialdehyde
      (MDA) as well as content of protein carbonyls in Ig G were measured. Plasma
      levels of retinol, tocopherols and carotenoids were significantly higher in group
      HI than in group LI subjects independent of age and gender. MDA levels were
      inversely correlated with vitamin A and alpha-carotene. Protein carbonyls were
      inversely correlated with gamma-tocopherol. In the elderly, a higher daily intake
      of fruits and vegetables is associated with an improved antioxidant status in
      comparison to subjects consuming diets poor in fruits and vegetables.
      Modification of nutritional habits among other lifestyle changes should be
      encouraged to lower prevalence of disease risk factors in later life.

PMID- 16277765
TI  - Influence of beta(2)-adrenoceptor gene polymorphisms on diet-induced
      thermogenesis.
AB  - The sympathetic nervous system is involved in the control of energy metabolism
      and expenditure. Diet-induced thermogenesis is mediated partly by the ss
      adrenergic component of this system. The aim of the present study was to
      investigate the role of genetic variation in the beta(2)-adrenoceptor in diet
      induced thermogenesis. Data from twenty-four subjects (fourteen men and ten
      women; BMI 26.7(sem 0.8) kg/m(2); age 45.2(sem1.4) years) with different
      polymorphisms of the beta(2)-adrenoceptor at codon 16 (Gly16Gly, Gly16Arg or
      Arg16Arg) were recruited for this study. Subjects were given a high-carbohydrate
      liquid meal, and the energy expenditure, respiratory exchange ratio, and plasma
      concentrations of NEFA, glycerol, glucose, insulin and catecholamines were
      measured before and over 4 h after the meal. The AUC of energy expenditure (diet
      induced thermogenesis) was not significantly different between polymorphism
      groups, nor was the response of any of the other measured variables to the meal.
      In a multiple regression model, the only variable that explained a significant
      proportion (32 %) of the variation in diet-induced thermogenesis was the increase
      in plasma adrenaline in response to the meal (P<0.05). The beta(2)-adrenoceptor
      codon16 polymorphisms did not contribute significantly. In conclusion, an
      independent contribution of the codon 16 polymorphism of the beta(2)-adrenoceptor
      gene to the variation in thermogenic response to a high-carbohydrate meal could
      not be demonstrated. The interindividual variation in thermogenic response to the
      meal was correlated with variations in the plasma adrenaline response to the
      meal.

PMID- 16277764
TI  - Human gut microbiota does not ferment erythritol.
AB  - Erythritol, a naturally occurring polyol, is gaining attention as a bulk
      sweetener for human nutrition. Industrially, it is produced from glucose by
      fermentation. From various studies it is known to be non-cariogenic. Moreover, it
      is rapidly absorbed in the small intestine and quantitatively excreted in the
      urine. Only about 10 % enters the colon. Earlier in vitro experiments showed that
      erythritol remained unfermented for a fermentation period of 12 h. In order to
      investigate whether fresh human intestinal microbiota is able to adapt its enzyme
      activities to erythritol, a 24 h lasting fermentation was carried out under well
      standardised in vitro conditions. For comparison maltitol, lactulose and blank
      (faecal inoculum only) were incubated as well. Fermentation patterns were
      established by following total gas production, hydrogen accumulation, changes in
      pH value, SCFA production and substrate degradation. Taking all fermentation
      parameters into account, erythritol turned out to be completely resistant to
      bacterial attack within 24 h, thus excluding an adaptation within that period.
      Since under in vivo conditions more easily fermentable substrates enter the colon
      continuously, it seems very unlikely that erythritol will be fermented in vivo.

PMID- 16277766
TI  - Protein secondary structures (alpha-helix and beta-sheet) at a cellular level and
      protein fractions in relation to rumen degradation behaviours of protein: a new
      approach.
AB  - Studying the secondary structure of proteins leads to an understanding of the
      components that make up a whole protein, and such an understanding of the
      structure of the whole protein is often vital to understanding its digestive
      behaviour and nutritive value in animals. The main protein secondary structures
      are the alpha-helix and beta-sheet. The percentage of these two structures in
      protein secondary structures influences protein nutritive value, quality and
      digestive behaviour. A high percentage of beta-sheet structure may partly cause a
      low access to gastrointestinal digestive enzymes, which results in a low protein
      value. The objectives of the present study were to use advanced synchrotron-based
      Fourier transform IR (S-FTIR) microspectroscopy as a new approach to reveal the
      molecular chemistry of the protein secondary structures of feed tissues affected
      by heat-processing within intact tissue at a cellular level, and to quantify
      protein secondary structures using multicomponent peak modelling Gaussian and
      Lorentzian methods, in relation to protein digestive behaviours and nutritive
      value in the rumen, which was determined using the Cornell Net Carbohydrate
      Protein System. The synchrotron-based molecular chemistry research experiment was
      performed at the National Synchrotron Light Source at Brookhaven National
      Laboratory, US Department of Energy. The results showed that, with S-FTIR
      microspectroscopy, the molecular chemistry, ultrastructural chemical make-up and
      nutritive characteristics could be revealed at a high ultraspatial resolution (
      approximately 10 microm). S-FTIR microspectroscopy revealed that the secondary
      structure of protein differed between raw and roasted golden flaxseeds in terms
      of the percentages and ratio of alpha-helixes and beta-sheets in the mid-IR range
      at the cellular level. By using multicomponent peak modelling, the results show
      that the roasting reduced (P<0.05) the percentage of alpha-helixes (from 47.1 %
      to 36.1 %: S-FTIR absorption intensity), increased the percentage of beta-sheets
      (from 37.2 % to 49.8 %: S-FTIR absorption intensity) and reduced the alpha-helix
      to beta-sheet ratio (from 0.3 to 0.7) in the golden flaxseeds, which indicated a
      negative effect of the roasting on protein values, utilisation and
      bioavailability. These results were proved by the Cornell Net Carbohydrate
      Protein System in situ animal trial, which also revealed that roasting increased
      the amount of protein bound to lignin, and well as of the Maillard reaction
      protein (both of which are poorly used by ruminants), and increased the level of
      indigestible and undegradable protein in ruminants. The present results
      demonstrate the potential of highly spatially resolved synchrotron-based infrared
      microspectroscopy to locate 'pure' protein in feed tissues, and reveal protein
      secondary structures and digestive behaviour, making a significant step forward
      in and an important contribution to protein nutritional research. Further study
      is needed to determine the sensitivities of protein secondary structures to
      various heat-processing conditions, and to quantify the relationship between
      protein secondary structures and the nutrient availability and digestive
      behaviour of various protein sources. Information from the present study arising
      from the synchrotron-based IR probing of the protein secondary structures of
      protein sources at the cellular level will be valuable as a guide to maintaining
      protein quality and predicting digestive behaviours.

PMID- 16277767
TI  - High-phosphorus diet stimulates receptor activator of nuclear factor-kappaB
      ligand mRNA expression by increasing parathyroid hormone secretion in rats.
AB  - The purpose of the present study was to clarify the manner by which the
      supplementation of high-P diet induces bone loss. Eighteen 4-week-old male Wistar
      strain rats were assigned randomly to three groups and fed diets containing three
      P levels (0.3, 0.9, and 1.5 %) for 21 d. A lower serum Ca concentration was
      observed in the rats fed on the 1.5 % P diet than in the other two groups. Serum
      P and parathyroid hormone concentrations and urinary excretion of C-terminal
      telopeptide of type I collagen were elevated with increasing dietary P levels.
      Serum osteocalcin concentration was increased in the rats fed on the 1.5 % P diet
      than in the other two groups. Bone formation rate of the lumbar vertebra was
      significantly increased in the two high-P groups than in the 0.3 % P group.
      Osteoclast number was significantly increased with increasing dietary P levels.
      Bone mineral content and bone mineral density of the femur and lumbar vertebra
      and ultimate compression load of the lumbar vertebra were decreased with
      increasing dietary P levels. Additionally, ultimate bending load of the femur was
      decreased in the rats fed on the 1.5 % P diet than in the other two groups.
      Receptor activator of NF-kappaB ligand (RANKL) mRNA expression in the femur was
      significantly higher with increasing dietary P levels. These results suggest that
      secondary hyperparathyroidism due to a high-P diet leads to bone loss via an
      increase in bone turnover. Furthermore, an increase in osteoclast number was
      caused by increased RANKL mRNA expression.

PMID- 16277768
TI  - A comparative study on the effects of oral amiodarone and trimeprazine, two in
      vitro retinyl ester hydrolase inhibitors, on the metabolic availability of
      vitamin A in rats.
AB  - Amiodarone, an antiarrhythmic drug, and trimeprazine, an antipsychotic drug, are
      both in vitro inhibitors of retinyl ester hydrolase. To determine whether these
      agents have deleterious effects on aspects of vitamin A metabolism, Brown Norway
      rats (n 18) were treated at clinically equivalent doses once daily for 26 d with
      either oral drug. On day 27, a tolerance test was used to determine whether these
      agents interfered with vitamin absorption. During the first 8 d, the plasma
      retinol level declined in all animals. Between days 12 and 27, it rose to near
      pre-treatment concentrations in the control and trimeprazine groups and remained
      relatively constant at low levels (P<0.001) in the amiodarone group. The
      intestinal absorption of vitamin A was reduced (P<0.05) in the amiodarone group
      compared with the placebo and trimeprazine groups, which did not differ
      significantly from each other. At the end of the 4-week treatment period, hepatic
      retinyl ester hydrolase activity was lower in the drug-dosed rats (P=0.06 for
      amiodarone) than in the controls. With regard to effects on liver reserves, drug
      treatment resulted in vitamin A depletion (P<0.019), and distinctive patterns of
      retinol and its esters were seen in response to dosing. In conclusion, amiodarone
      and trimeprazine have been shown to influence different aspects of retinoid
      metabolism, namely absorption, storage and transport. In clinical practice, the
      routine unmonitored use of these drugs and the suggestion that these agents be
      taken with meals are not recommended.

PMID- 16277769
TI  - A diet rich in phosphatidylethanolamine increases plasma homocysteine in mink: a
      comparison with a soybean oil diet.
AB  - The effects of high dietary levels of phosphatidylethanolamine (PE) on plasma
      concentrations of homocysteine (tHcy) have not previously been studied. Eighteen
      mink (Mustela vison) studied were fed one of three diets during a 25 d period in
      a parallel-group design. The compared diets had 0, 17 and 67 % extracted lipids
      from natural gas-utilising bacteria (LNGB), which were rich in PE. The group with
      0 % LNGB was fed a diet of 100 % soyabean oil (SB diet). Phospholipids are the
      main lipid components in LNGB and Methylococcus capsulatus is the main bacteria
      (90 %). The fasting plasma concentration of tHcy was significantly higher when
      the mink consumed the diet with 67 % LNGB than when they consumed the SB diet
      (P=0.039). A significantly lower glutathione peroxidase activity was observed in
      mink consuming the 17 % LNGB diet or the 67 % LNGB diet than was observed in mink
      fed the SB diet. The lack of significant differences in the level of plasma PE
      due to the diets indicates that most of the PE from the 67 % LNGB diet was
      converted to phosphatidylcholine (PC) in the liver. It has previously been
      hypothesised that phosphatidylethanolamine N-methyltransferase is an important
      source of tHcy. The present results indicate that plasma tHcy is at least partly
      regulated by phospholipid methylation from PE to PC. This methylation reaction is
      a regulator of physiological importance.

PMID- 16277770
TI  - Effect of ruminal administration of Escherichia coli wild type or a genetically
      modified strain with enhanced high nitrite reductase activity on methane emission
      and nitrate toxicity in nitrate-infused sheep.
AB  - The effects of two kinds of Escherichia coli (E. coli) strain, wild-type E. coli
      W3110 and E. coli nir-Ptac, which has enhanced NO(2) reduction activity, on oral
      CH(4) emission and NO(3) toxicity in NO(3)-treated sheep were assessed in a
      respiratory hood system in a 4 x 6 Youden square design. NO(3) (1.3 g
      NaNO(3)/kg(0.75) body weight) and/or E. coli strains were delivered into the
      rumen through a fistula as a single dose 30 min after the morning meal.
      Escherichia coli cells were inoculated for sheep to provide an initial E. coli
      cell density of optical density at 660 nm of 2, which corresponded to 2 x 10(10)
      cells/ml. The six treatments consisted of saline, E. coli W3110, E. coli nir
      Ptac, NO(3), NO(3) plus E. coli W3110, and NO(3) plus E. coli nir-Ptac. CH(4)
      emission from sheep was reduced by the inoculation of E. coli W3110 or E. coli
      nir-Ptac by 6 % and 12 %, respectively. NO(3) markedly inhibited CH(4) emission
      from sheep. Compared with sheep given NO(3) alone, the inoculation of E. coli
      W3110 to NO(3)-infused sheep lessened ruminal and plasma toxic NO(2) accumulation
      and blood methaemoglobin production, while keeping ruminal methanogenesis low.
      Ruminal and plasma toxic NO(2) accumulation and blood methaemoglobin production
      in sheep were unaffected by the inoculation of E. coli nir-Ptac. These results
      suggest that ruminal methanogenesis may be reduced by the inoculation of E. coli
      W3110 or E. coli nir-Ptac. The inoculation of E. coli W3110 may abate NO(3)
      toxicity when NO(3) is used to inhibit CH(4) emission from ruminants.

PMID- 16277771
TI  - Effect of aerobic exercise on lipaemia and its fatty acid profile after a meal of
      moderate fat content in eumenorrhoeic women.
AB  - Exercise prior to eating has repeatedly been shown to reduce postprandial
      lipaemia. The aim of the present study was to investigate whether this effect was
      manifest in the presence of two factors that independently mitigate postprandial
      lipaemia: eumenorrhoea and moderate fat intake. Eight healthy eumenorrhoeic
      rowers consumed a meal of moderate fat content (35 % total energy, 0.66 g/kg body
      mass) 14 h after having either rowed at 55 % of maximal aerobic power (81 % of
      maximal heart rate) for 80 min or rested. Both trials were performed during the
      luteal phase. Blood samples were drawn before the meal and for 8 h postprandially
      for the measurement of individual fatty acids in the triacylglycerol and NEFA
      fractions, as well as of glucose, insulin and oestradiol. Plasma oestradiol
      concentrations were not significantly different in the two trials. The
      postprandial lipaemic response, expressed as either plasma triacylglycerol
      concentration or area under the triacylglycerol-time curve, was 35 % lower
      (P<0.05) after exercise. The postprandial glycaemic and insulinaemic responses
      were also lower, indicating increased insulin sensitivity, whereas the NEFA
      response was higher, suggesting a lower entrapment of dietary fatty acids in
      adipose tissue after exercise. Finally, exercise increased the proportion of
      unsaturated:saturated NEFA during the postprandial period. In conclusion, aerobic
      exercise performed 14 h before a moderate-fat meal reduced postprandial lipaemia
      in women in the luteal phase. This effect shows the potential of exercise to
      mitigate even moderate lipaemic responses in eumenorrhoeic women.

PMID- 16277772
TI  - Short-chain fatty acid formation in the hindgut of rats fed oligosaccharides
      varying in monomeric composition, degree of polymerisation and solubility.
AB  - The contents of short-chain fatty acids were investigated in rats fed lactitol,
      lactulose and four fructo-oligosaccharides of different degree of polymerisation
      and solubility. Fructo-oligosaccharides with a low degree of polymerisation (2-8)
      generated the highest levels of butyric acid all along the hindgut, whereas
      fructo-oligosaccharides with a high degree of polymerisation (10-60) generated
      the highest levels of propionic acid. These specific differences were also
      generally reflected in the caecal pools and molar proportions of short-chain
      fatty acids. The lower solubility of the fructo-oligosaccharides was related to a
      lower degree of caecal fermentation. Lactulose and lactitol yielded high
      proportions of acetic acid and low proportions of butyric acid. It is concluded
      that both the degree of polymerisation and the solubility may affect short-chain
      fatty acid formation, whereas the fructose content per se seem to be of less
      importance. This may be of interest when designing foods with specific health
      effects.

PMID- 16277773
TI  - Effect of acetic acid feeding on the circadian changes in glycogen and
      metabolites of glucose and lipid in liver and skeletal muscle of rats.
AB  - The aim of the present study is to investigate the effect of acetic acid feeding
      on the circadian changes in glycogen concentration in liver and skeletal muscle.
      Rats were provided meal once daily (09.00-13.00 hours) for 10 d. On the 11th day,
      they were either killed immediately or given 9 g diet containing either 0
      (control) or 0.7 g/kg-diet acetic acid beginning at 09.00 hours for 4 h, as in
      the previous regimen. Rats in the fed group were killed at 4, 8 or 24 h after the
      start of feeding. At 4 h after the start of feeding, the acetic acid group had
      significantly greater liver and gastrocnemius muscle glycogen concentrations
      (P<0.05). Also, at this same point, liver xylulose-5-phosphate, a key stimulator
      of glycolysis, the ratio of fructose-1,6-bisphosphate to fructose-6-phosphate in
      skeletal muscle, which reflects phosphofructokinase-1 activity, and liver malonyl
      CoA, an allosteric inhibitor of carnitine palmitoyl-transferase, were
      significantly lower in the acetic acid group than in the control group (P<0.05).
      In addition, the acetic acid group had a significantly lower serum lactate
      concentration and lower ratio of insulin to glucagon than the control group at
      the same point (P<0.05). We conclude that a diet containing acetic acid may
      enhance glycogen repletion but not induce supercompensation, a large increase in
      the glycogen level that is beneficial in improving performance, in liver and
      skeletal muscle by transitory inhibition of glycolysis. Further, we indicate the
      possibility of a transient enhancement of fatty acid oxidation in liver by acetic
      acid feeding.

PMID- 16277774
TI  - The importance of dietary composition for efficacy of iron absorption measured in
      a whole diet that includes rye bread fortified with ferrous fumerate: a
      radioisotope study in young women.
AB  - Fe absorption is affected by many dietary factors. The objective of the present
      study was to measure the effects of high v. low content of vitamin C, meat and
      phytic acid in whole diets with Fe-fortified bread on the efficacy of Fe
      absorption. Thirty-two healthy women with low Fe stores were randomised to three
      groups, each of which was given two of six test diets containing either low/high
      amounts of vitamin C, meat or phytic acid, respectively, in a cross-over design.
      Each diet was served throughout a 5 d period. Fe-fortified rye bread,
      extrinsically labelled with (59)Fe, was given with all main meals. Fe absorption
      was determined from whole-body counter measurements of (59)Fe retention. The
      fractional non-haem Fe absorption (corrected to a 40 % standard absorption by
      measurements from the reference dose) was 1.9 % v. 3.4 % (P=0.04) for the
      low/high vitamin C diets, 3.0 % v. 3.5 % (P=0.58) on the low/high meat diets and
      4.9 % v. 3.8 % (P=0.24) on the low/high phytic acid diet, respectively. The total
      Fe absorbed (geometric mean with standard error) varied from 0.43 (se 0.11) mg
      from the diet with lowest bioavailability to 1.09 (se 0.18) mg from the diet with
      highest bioavailability (P<0.001). The present whole-diet study indicates that
      diet composition is a strong predictor of Fe absorption. In the diet with a low
      content of enhancers and a high content of inhibitors, vitamin C improved non
      haem Fe absorption. The total Fe absorption varied 2.5-fold after small
      alterations of the content of enhancers and inhibitors in the diet.

PMID- 16277775
TI  - Evidence of unmetabolised folic acid in cord blood of newborn and serum of 4-day
      old infants.
AB  - Oral folic acid above certain threshold doses results in unmetabolised folic acid
      in serum. This raises a number of public health safety issues, principally the
      potential to mask pernicious anaemia; more recently the theoretical potential for
      high-dose folic acid to promote cancer has been highlighted. In this paper we set
      out to examine the appearance of unmetabolised folic acid both in cord blood from
      newborn full-term and premature infants and serum from 4-d-old infants post
      formula feeding. Blood was collected from the umbilical cord of eleven infants in
      the delivery room immediately after birth. A follow-up serum sample (n 9) was
      collected 4 d later from infants post-formula feeding. We detected unmetabolised
      folic acid in cord blood from all infants at birth. In addition, unmetabolised
      folic acid was present in serum of seven infants post-formula feeding, six of
      which had increased from birth. Our results imply that infants in Ireland, which
      does not yet have mandatory fortification, could potentially have circulatory
      unmetabolised folic acid at the time of birth. We do not know if the presence of
      folic acid in cord blood will have any adverse consequences. However, if
      theoretical safety concerns are borne out by future research, the likelihood is
      that the longer the exposure the more likely the potential for harm. This would
      also be the case in infants exposed to unmetabolised folic acid as a result of
      formula feeding.

PMID- 16277776
TI  - Short-term effect of egg-white hydrolysate products on the arterial blood
      pressure of hypertensive rats.
AB  - In the present study we evaluate the blood pressure-lowering effect of the
      following products: the hydrolysate obtained from egg white (EW) by enzymatic
      treatment with pepsin (HEW), the peptide fraction of HEW with molecular mass
      lower than 3000 Da (HEW<3000 Da), and three peptide sequences isolated from
      HEW<3000 Da (Tyr-Ala-Glu-Glu-Arg-Tyr-Pro-Ile-Leu: YAEERYPIL); (Arg-Ala-Asp-His
      Pro-Phe-Leu: RADHPFL); and (Ile-Val-Phe (IVF)). These peptides, and also HEW and
      HEW<3000 Da, had been characterized previously in vitro as potent inhibitors of
      angiotensin-converting enzyme (ACE). EW and the products mentioned earlier were
      orally administered by gastric intubation, to 17-20-week-old male spontaneously
      hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. We measured the
      systolic blood pressure (SBP) and the diastolic blood pressure (DBP) of the rats
      by the tail cuff method before administration and also 2, 4, 6, 8 and 24 h post
      administration. Distilled water served as negative control, and we used captopril
      (50 mg/kg) as positive control to carry out similar experiments with a known ACE
      inhibitor. HEW, HEW<3000 Da and the three peptide sequences decreased SBP and DBP
      in SHR but they did not modify these variables in WKY rats. The peptide sequences
      YAEERYPIL, RADHPFL and IVF showed a potency to decrease blood pressure greater
      than HEW or HEW<3000 Da. The results obtained suggest that the studied products
      could be used as a functional food with potential therapeutic benefit in the
      prevention and treatment of hypertension.

PMID- 16277777
TI  - Rats treated with oleoyl-oestrone maintain glucidic homeostasis: comparisons with
      a pair-fed model.
AB  - To determine whether or not the weight (and fat) loss induced by oleoyl-oestrone
      treatment results only as a consequence of decreased food intake, we compared
      treated animals with a pair-fed model. To this end, Wistar female rats received
      daily oral gavages of 10 mumol/kg per d oleoyl-oestrone in sunflower oil, or
      vehicle alone for 10 or 20 d. A second group of rats received the gavage of
      sunflower oil and the same amount of food ingested as the oleoyl-oestrone-treated
      animals (pair-fed group). Rats treated with oleoyl-oestrone maintained glucidic
      metabolism homeostasis despite a marked decrease in adipose tissue weight
      (P<0.001). Pair-fed rats exhibited a different pattern, comparable to short-term
      starvation, with greatly decreased glycogen stores (P<0.0001). The most
      significant effects were detected in the 10 d period groups. Oleoyl-oestrone
      affected the activity of the ponderostat system not only by decreasing appetite
      but also by modifying energy partition: treated animals maintained their glucose
      and energy homeostasis despite decreased food intake and the massive depletion of
      lipid stores.

PMID- 16277778
TI  - Conjugated linoleic acid enhanced the immune function in broiler chicks.
AB  - This study was undertaken to investigate the growth performance and immune
      responses of broiler chicks fed diets supplemented with conjugated linoleic acid
      (CLA). Two hundred and forty day-old Arbor Acre male broiler chicks were randomly
      allotted into four dietary treatments with different inclusion levels of CLA (0,
      2.5, 5.0 or 10.0 g pure CLA/kg) for 6 weeks. Growth performance, lysozyme
      activity, peripheral blood mononuclear cell (PBMC) proliferation, prostaglandin
      E2 (PGE2) synthesis and antibody production were investigated. There were no
      significant differences in growth performance among treatments (P>0.05). Chicks
      fed 10.0 g CLA/kg diet produced 40 % and 49 % more lysozyme activity in serum and
      spleen than the control group at 21 d of age (P<0.05). Dietary CLA enhanced the
      PBMC proliferation in response to concanavalin A at the age of 21 and 42 d
      (P<0.05). Systemic and peripheral blood lymphocytic synthesis of PGE2 in chicks
      fed 10.0 g CLA/kg diet was significantly decreased by 57 % and 42 % compared to
      chicks fed control diet (P<0.05). Antibody production to sheep red blood cell and
      bovine serum albumin were elevated in either 2.5 or 10.0 g CLA/kg dietary
      treatments (P<0.05). The results indicated dietary CLA could enhance the immune
      response in broiler chicks, but did not alter the growth performance.

PMID- 16277779
TI  - Humoral defence improvement and haematopoiesis stimulation in sows and offspring
      by oral supply of shark-liver oil to mothers during gestation and lactation.
AB  - Shark-liver oil (SLO) contains two bioactive lipids: alkylglycerols and n-3 PUFA.
      Alkylglycerols have immunostimulating and haematopoietic properties, while n-3
      PUFA are essential for optimal neonatal development. We investigated the
      beneficial effects of dietary supplementation with 32 g SLO/d to twelve pregnant
      and then lactating sows (from day 80 of pregnancy to weaning) on the growth and
      immune status of their offspring, compared with a control group. Sows were
      vaccinated against Aujeszky's disease 21 d before term. Blood samples were
      collected from sows before treatment, on delivery and 14 d later, and from five
      piglets per litter on days 2, 21 and 36 after birth; colostrum and milk samples
      were collected 12 h, 14 and 28 d postpartum. Compared with controls, supplemented
      sows had higher levels of both erythrocytes and Hb in their blood, and higher
      concentrations of IgG, alkylglycerols and n-3 PUFA in their mammary secretions.
      In piglets from supplemented sows, leucocytes and IgG were higher.
      Supplementation with SLO resulted in an increase in Aujeszky antibodies in both
      blood and colostrum of sows after vaccination, together with an increase in
      Aujeszky antibodies in piglet blood. Our findings demonstrate that improvement of
      both passive and active immune status in piglets is related to the consumption of
      alkylglycerols associated with n-3 PUFA in the sow diet. The overall improvement
      in offspring health status by SLO supplementation to the mother could be of
      interest for optimisation of the lipid diet during and after pregnancy.

PMID- 16277780
TI  - Protein recycling in growing rabbits: contribution of microbial lysine to amino
      acid metabolism.
AB  - To study the absorption of microbial lysine in growing rabbits, a labelled diet
      (supplemented with (15)NH4Cl) was administered to six animals (group ISOT); a
      control group (CTRL, four rabbits) received a similar, but unlabelled, diet.
      Diets were administered for 30 d. An additional group of six animals were fed the
      unlabelled diet for 20 d and then the labelled diet for 10 d while wearing a neck
      collar to avoid caecotrophy (group COLL), in order to discriminate it from direct
      intestinal absorption. At day 30 animals were slaughtered and caecal bacteria and
      liver samples taken. The (15)N enrichment in amino acids of caecal bacteria and
      liver were determined by GC-combustion/isotope ratio MS. Lysine showed a higher
      enrichment in caecal microflora (0.925 atom% excess, APE) than liver (0.215 APE)
      in group ISOT animals, confirming the double origin of body lysine: microbial and
      dietary. The COLL group showed a much lower enrichment in tissue lysine (0.007
      (se 0.0029) APE for liver). Any enrichment in the latter animals was due to
      direct absorption of microbial lysine along the digestive tract, since recycling
      of microbial protein (caecotrophy) was avoided. In such conditions liver
      enrichment was low, indicating a small direct intestinal absorption. From the
      ratio of [(15)N]lysine enrichment between liver and bacteria the contribution of
      microbes to body lysine was estimated at 23 %, with 97 % of this arising through
      caecotrophy. Absorption of microbial lysine through caecotrophy was 119 (se 4.0)
      mg/d, compared with 406 (se 1.8) mg/d available from the diet. This study
      confirms the importance of caecotrophy in rabbit nutrition (15 % of total protein
      intake).

PMID- 16277781
TI  - The effect of enzyme treatment on the in vitro fermentation of lucerne incubated
      with equine faecal inocula.
AB  - A series of experiments was conducted to determine the effects of a fibrolytic
      enzyme preparation (enzyme 1; E1) on the in vitro fermentation of lucerne
      incubated with equine faecal inocula. In experiment 1, high-temperature-dried
      (HT) lucerne was treated with five levels of E1 (0 to 2.4 ml/g DM) and incubated
      at 50 degrees C for 20 h. Samples then received a simulated foregut digestion
      (SFD) treatment before DM and NSP analysis. In experiment 2, HT lucerne was
      treated with the same enzyme levels used in experiment 1. Samples were then split
      into two groups; plus or minus an SFD treatment before in vitro fermentation
      using an equine faecal inoculum. In experiment 3, fresh and wilted lucerne were
      treated with the same levels of E1 as experiments 1 and 2, incubated at 50
      degrees C for 20 h, then fermented in vitro. For experiment 4, fresh and wilted
      lucerne were treated with low levels (0 to 0.008 ml/g DM) of E1 before
      fermentation. E1 significantly (P<0.05) enhanced DM and NSP losses from HT
      lucerne following SFD treatment compared with the control. High levels of E1
      significantly (P<0.05) enhanced the rate, but not extent, of fermentation of HT,
      wilted and fresh lucerne; however, low levels of E1 were ineffective. At higher
      application levels, E1 appears to have considerable potential to enhance the
      nutritive value of lucerne for horses. Information on the fermentation kinetics
      of the substrates was valuable; all end-point measurements showed no effect of
      enzyme treatment.

PMID- 16277782
TI  - Effects of infant formula containing a mixture of galacto- and fructo
      oligosaccharides or viable Bifidobacterium animalis on the intestinal microflora
      during the first 4 months of life.
AB  - Adding prebiotics or probiotics to infant formula to improve the intestinal flora
      of formula-fed infants is considered to be a major innovation. Several companies
      have brought relevant formulations onto the market. However, comparative data on
      the effects of pre- and probiotics on the intestinal microflora of infants are
      not available. The present study aimed to compare the effects of infant formula
      containing a mixture of galacto- and fructo-oligosaccharides or viable
      Bifidobacterium animalis on the composition and metabolic activity of the
      intestinal microflora. Before birth, infants were randomised and double blindly
      allocated to one of three formulas. The prebiotic (GOS/FOS) group (n 19) received
      regular infant formula supplemented with a mixture of galacto-oligosaccharides
      and fructo-oligosaccharides (6 g/l). The probiotic (Bb-12) group (n 19) received
      the same formula supplemented with 6.0x10(10) viable cells of B. animalis per
      litre. The standard group (n 19) received non-supplemented regular formula. A
      group of sixty-three breast-fed infants was included as a reference group. Faecal
      samples were taken at postnatal day 5 and 10, and week 4, 8, 12 and 16. Compared
      with the groups fed Bb-12 and standard formula, the GOS/FOS formula group showed
      higher faecal acetate ratio (69.7 % (sem 2.7), 69.9 % (sem 3.9) and 82.2 % (sem
      5.3); P<0.05) and lactate concentration (11.3 (sem 7.9), 3.1 (sem 2.3) and 34.7
      (sem 10.7) mmol/kg faeces) and lower pH (6.6 (sem 0.2), 7.1 (sem 0.2) and 5.6
      (sem 0.2); P<0.05) at 16 weeks. Differences in percentage of bifidobacteria
      between the GOS/FOS (59.2 % (sem 7.7)), Bb-12 (52.7 % (sem 8.0)) and the standard
      (51.8 % (sem 6.4)) groups were not statistically significant at 16 weeks. Feeding
      infants GOS/FOS formula resulted in a similar effect on metabolic activity of the
      flora as in breast-fed infants. In the Bb-12 group, composition and metabolic
      activity of the flora were more similar to those of the standard group.

PMID- 16277783
TI  - Conjugated linoleic acid increased C-reactive protein in human subjects.
AB  - We previously showed that conjugated linoleic acid (CLA) increases 15-keto
      dihydro-prostaglandin F2alpha, a marker for cyclooxygenase-mediated lipid
      peroxidation and thus an indicator of cyclooxygenase-mediated inflammation. The
      aim of the present study was to investigate the effects of CLA on other
      indicators of inflammation in human subjects, including C-reactive protein, TNF
      alpha, TNF-alpha receptors 1 and 2, and vascular cell adhesion molecule-1. In a
      double-blind, placebo-controlled study, fifty-three human subjects were
      supplemented with a mixture (4.2 g/d) of the isomers cis-9,trans-11 CLA and trans
      10,cis-12 CLA or control oil for 3 months. CLA supplementation increased levels
      of C-reactive protein (P=0.003) compared with the control group. However, no
      changes in TNF-alpha, TNF-alpha receptors 1 and 2, and vascular cell adhesion
      molecule-1 were detected.

PMID- 16277784
TI  - Glycaemic index and glycaemic load in the diet of healthy schoolchildren: trends
      from 1990 to 2002, contribution of different carbohydrate sources and
      relationships to dietary quality.
AB  - Despite intense discussion of the glycaemic index (GI) and glycaemic load (GL)
      concepts, data on the GI or GL levels in the diet of children are scarce. The
      present analysis determined trends in the levels of GI or GL of healthy children
      from 1990 to 2002 and examined the contribution of carbohydrate (CHO) sources to
      the overall GL, and the relationships of the GI and GL to the overall dietary
      quality. The analysis includes three cohorts of participants from the Dortmund
      Nutritional and Anthropometrical Longitudinally Designed study, aged 7-8 years in
      1990 (n 53), 1996 (n 46) and 2002 (n 56). A GI value was assigned to all CHO
      foods recorded over three consecutive days. In comparison with 1990, 7-8-year-old
      children in 2002 had slightly higher GI (56.5 v. 55.1 %; P=0.03) and GL (17.5 v.
      16.7 g/MJ; P=0.04) levels. In all three time periods the combined contribution of
      the 'tolerated food groups' (i.e. sweets, soft drinks, cakes and cookies, and
      salty snacks) to the overall GL exceeded that of bread and rolls (1990, 31 v. 24
      %; 1996, 29 v. 31 %; 2002, 28 v. 25 %). Conversely, rice and fried or mashed
      potatoes had only a minor impact. Children in the lowest GI tertile, but not
      those in the lowest GL tertile, had a better nutrient profile and a more
      favourable food choice. In conclusion, partial replacement of high-GI 'tolerated
      food groups' for low-GI foods would help to reverse the slight recent increases
      in GI and GL, and to improve the overall dietary quality of 7-8-year-old
      children.

PMID- 16277785
TI  - A provisional database for the silicon content of foods in the United Kingdom.
AB  - Si may play an important role in bone formation and connective tissue metabolism.
      Although biological interest in this element has recently increased, limited
      literature exists on the Si content of foods. To further our knowledge and
      understanding of the relationship between dietary Si and human health, a reliable
      food composition database, relevant for the UK population, is required. A total
      of 207 foods and beverages, commonly consumed in the UK, were analysed for Si
      content. Composite samples were analysed using inductively coupled plasma-optical
      emission spectrometry following microwave-assisted digestion with nitric acid and
      H(2)O(2). The highest concentrations of Si were found in cereals and cereal
      products, especially less refined cereals and oat-based products. Fruit and
      vegetables were highly variable sources of Si with substantial amounts present in
      Kenyan beans, French beans, runner beans, spinach, dried fruit, bananas and red
      lentils, but undetectable amounts in tomatoes, oranges and onions. Of the
      beverages, beer, a macerated whole-grain cereal product, contained the greatest
      level of Si, whilst drinking water was a variable source with some mineral waters
      relatively high in Si. The present study provides a provisional database for the
      Si content of UK foods, which will allow the estimation of dietary intakes of Si
      in the UK population and investigation into the role of dietary Si in human
      health.

PMID- 16277786
TI  - Dietary silicon intake in post-menopausal women.
AB  - Si has been suggested as an essential element, and may be important in optimal
      bone, skin and cardiovascular health. However, there are few estimates of dietary
      Si intakes in man, especially in a UK population. Following the development of a
      UK food composition database for Si, the aim of the present study was to
      investigate dietary intakes of Si amongst healthy women aged over 60 years and to
      identify important food sources of Si in their diet. Healthy, post-menopausal
      female subjects (>60 years of age; n 209) were recruited from the general
      population around Dundee, Scotland as part of an unrelated randomised controlled
      intervention study where dietary intake was assessed using a self-administered,
      semi-quantitative food-frequency questionnaire at five time-points over a 2-year
      period. Food composition data on the Si content of UK foods was used to determine
      the Si content of food items on the food-frequency questionnaire. Mean Si intake
      was 18.6 (sd 4.6) mg and did not vary significantly across the 2 years of
      investigation. Cereals provided the greatest amount of Si in the diet (about 30
      %), followed by fruit, beverages (hot, cold and alcoholic beverages combined) and
      vegetables; together these foods provided over 75 % about Si intake. Si intakes
      in the UK appear consistent with those reported previously for elderly women in
      Western populations, but lower than those reported for younger women or for men.

PMID- 16277787
TI  - Goitre decline in Italy and contribution of the silent and active prophylaxis.
AB  - Goitre has been declining in Italy since the 1970s and because active prophylaxis
      (AP) has been very limited, it has been suggested that in most places the decline
      was due to silent prophylaxis (SP). SP is related to the natural increase in
      iodine intake because of higher consumption of iodine-rich products associated
      with socioeconomic development. The hypothesis tested in the present study is
      that SP has increased iodine intake in Italy with subsequent reduction of goitre
      and that such changes can be quantified. The analysis is based on surveys carried
      out between the 1970s and the 1990s where goitre and urinary iodine, a proxy of
      consumption, were measured in schoolchildren. The contribution of the SP can be
      quantified in an annual increase in urinary iodine excretion between 2.1 and 4
      microg/l, and an annual decline in goitre prevalence between 2.1 and 3.6 %. In
      the few areas with AP, there was an annual increase in urinary iodine between 6.5
      and 13.1 microg/l, while the average annual decline of goitre was between 4.4 and
      10 %. The present results could be used by policy-makers to predict the future
      trends in the excretion of urinary iodine and prevalence of goitre in Italy with
      and without AP. AP is about three times faster than SP in increasing iodine
      intake, but policy-makers should estimate the incremental cost-effectiveness of
      AP net of the iodine increase already occurring naturally with the SP.

PMID- 16277788
TI  - Whole-grain intake of British young people aged 4-18 years.
AB  - Inverse associations between whole-grain food consumption and risk of CVD, some
      cancers and type 2 diabetes have been reported. However, there are few reports of
      whole-grain intake, particularly among young people. The objective of the present
      study was to estimate whole-grain intake in a nationally representative sample of
      young people aged 4-18 years living in Great Britain. Whole-grain intake was
      estimated using 7 d weighed dietary records from 1583 young people who
      participated in the cross-sectional National Diet and Nutrition Survey in 1997.
      Whole-grain intake was quantified from the consumption of all foods containing >
      or =10 % whole-grain content. Median whole-grain intake was 7 g/d (interquartile
      range 0-19 g/d), with a corresponding mean of 13 (sd 18) g/d. Intake was
      significantly lower among young people whose head of household had a manual
      occupation, but did not differ significantly by sex, age, region or season. There
      was no whole-grain intake for 27 % of participants. The percentages for less than
      one and less than three 16 g amounts of whole-grain intake per d were 70 and 94,
      respectively, while corresponding percentages based on 20 g amounts were 76 and
      97. Foods with <51 % whole-grain content provided 28 % of whole-grain intake
      overall, with a higher percentage in older adolescents. The main sources of whole
      grain intake were breakfast cereals (56 %) and bread (25 %). The present study
      provides the first quantification of absolute whole-grain intake from all
      significant food sources in any representative age group in the UK. Although
      there is some debate regarding the quantity of whole grains required for good
      health, whole-grain intake among British young people is low.

PMID- 16277789
TI  - Misreporting of energy: prevalence, characteristics of misreporters and influence
      on observed risk estimates in the Malmo Diet and Cancer cohort.
AB  - The present study investigates the prevalence of misreporting of energy in the
      Malmo Diet and Cancer cohort, and examines anthropometric, socio-economic and
      lifestyle characteristics of the misreporters. Further, the influence of
      excluding misreporters on risk estimates of post-menopausal breast cancer was
      examined. Information of reported energy intake (EI) was obtained from a modified
      diet history method. A questionnaire provided information on lifestyle and socio
      economic characteristics. Individual physical activity level (PAL) was calculated
      from self-reported information on physical activity at work, leisure time
      physical activity and household work, and from estimates of hours of sleeping,
      self-care and passive time. Energy misreporting was defined as having a ratio of
      EI to BMR outside the 95 % CI limits of the calculated PAL. Logistic regression
      analysed the risk of being a low-energy reporter or a high-energy reporter.
      Almost 18 % of the women and 12 % of the men were classified as low-energy
      reporters, 2.8 % of the women and 3.5 % of the men were classified as high-energy
      reporters. In both genders high BMI, large waist circumference, short education
      and being a blue-collar worker were significantly associated with low-energy
      reporting. High-energy reporting was significantly associated with low BMI,
      living alone and current smoking. The results add support to the practice of
      energy adjustment as a means to reduce the influence of errors in risk
      assessment.

PMID- 16277790
TI  - Intra- and interindividual variability of resting energy expenditure in healthy
      male subjects -- biological and methodological variability of resting energy
      expenditure.
AB  - The objective of the present study was to investigate the contribution of intra
      individual variance of resting energy expenditure (REE) to interindividual
      variance in REE. REE was measured longitudinally in a sample of twenty-three
      healthy men using indirect calorimetry. Over a period of 2 months, two
      consecutive measurements were done in the whole group. In subgroups of seventeen
      and eleven subjects, three and four consecutive measurements were performed over
      a period of 6 months. Data analysis followed a standard protocol considering the
      last 15 min of each measurement period and alternatively an optimised protocol
      with strict inclusion criteria. Intra-individual variance in REE and body
      composition measurements (CV(intra)) as well as interindividual variance
      (CV(inter)) were calculated and compared with each other as well as with REE
      prediction from a population-specific formula. Mean CV(intra) for measured REE
      and fat-free mass (FFM) ranged from 5.0 to 5.6 % and from 1.3 to 1.6 %,
      respectively. CV(intra) did not change with the number of repeated measurements
      or the type of protocol (standard v. optimised protocol). CV(inter) for REE and
      REE adjusted for FFM (REE(adj)) ranged from 12.1 to 16.1 % and from 10.4 to 13.6
      %, respectively. We calculated total error to be 8 %. Variance in body
      composition (CV(intra) FFM) explains 19 % of the variability in REE(adj), whereas
      the remaining 81 % is explained by the variability of the metabolic rate
      (CV(intra) REE). We conclude that CV(intra) of REE measurements was neither
      influenced by type of protocol for data analysis nor by the number of repeated
      measurements. About 20 % of the variance in REE(adj) is explained by variance in
      body composition.

PMID- 16277791
TI  - Effect on appetite control of minor cereal and pseudocereal products.
AB  - Recent findings suggest that Western diets based on highly palatable foods are
      likely to be much less satiating than more traditional diets or those typical of
      less developed countries. In particular, some alternative crops (for example,
      buckwheat, oat, barley, spelt, rye, quinoa, amaranth) seem to be of great
      nutritional interest and to represent important recipes for healthier and typical
      regional foods. The objective of the present study was to investigate the effect
      on subsequent food intake and feelings of satiety of alternative oat bread, oat
      and buckwheat pasta and of quinoa as compared with their wheat counterparts and
      rice, respectively. Three different experiments (one specific for each
      alternative crop food) were conducted, all with a within-subjects design. The
      preloading paradigm strategy was used. Results showed that preload energy level
      influenced total energy intake (preload plus ad libitum test meal intake), larger
      preloads inducing more eating than smaller preloads. No effect of formulation was
      observed on energy intake, as the consumption of alternative crop formulations
      did not decrease the total energy intake as compared with that of the
      counterparts. Satiating efficiency indices (SEI) for alternative crop foods were
      higher with respect to traditional cereal foods. In particular, white bread was
      the least satisfying food (SEI =0.2) and the different time of consumption (for
      lunch or as a snack) did not affect energy intake. In conclusion, oat or
      buckwheat formulations, and also quinoa, may be exploited for their potential
      impact on eating behaviour, particularly considering they are good sources of
      functional substances.

PMID- 16277792
TI  - Does regular walnut consumption lead to weight gain?
AB  - Studies consistently show the beneficial effects of eating nuts, but as high
      energy foods, their regular consumption may lead to weight gain. We tested if
      daily consumption of walnuts (approximately 12 % energy intake) for 6 months
      would modify body weight and body composition in free-living subjects. Ninety
      participants in a 12-month randomized cross-over trial were instructed to eat an
      allotted amount of walnuts (28-56 g) during the walnut-supplemented diet and not
      to eat them during the control diet, with no further instruction. Subjects were
      unaware that body weight was the main outcome. Dietary compliance was about 95 %
      and mean daily walnut consumption was 35 g during the walnut-supplemented diet.
      The walnut-supplemented diet resulted in greater daily energy intake (557 kJ (133
      kcal)), which should theoretically have led to a weight gain of 3.1 kg over the 6
      month period. For all participants, walnut supplementation increased weight (0.4
      (se 0.1) kg), BMI (0.2 (se 0.1) kg/m(2)), fat mass (0.2 (se 0.1) kg) and lean
      mass (0.2 (se 0.1) kg). But, after adjusting for energy differences between the
      control and walnut-supplemented diets, no significant differences were observed
      in body weight or body composition parameters, except for BMI (0.1 (se 0.1)
      kg/m(2)). The weight gain from incorporating walnuts into the diet (control-
      >walnut sequence) was less than the weight loss from withdrawing walnuts from the
      diet (walnut-->control sequence). Our findings show that regular walnut intake
      resulted in weight gain much lower than expected and which became non-significant
      after controlling for differences in energy intake.

PMID- 16277793
TI  - Postprandial hypotension in the elderly: what is the metabolic chain of events?

PMID- 16277794
TI  - The 'new nutrition' and physical activity.

PMID- 16277795
TI  - Out of the box.

PMID- 16277796
TI  - Use of national food balance data to estimate the adequacy of zinc in national
      food supplies: methodology and regional estimates.
AB  - OBJECTIVES: Adequate zinc nutriture is critically important for human health, but
      the development of programmes to control zinc deficiency is limited by the lack
      of reliable information on population zinc status. The present analyses were
      conducted to: (1) estimate the absorbable zinc content of national food supplies;
      (2) compare this information with theoretical population requirements for zinc;
      and (3) use these results to predict national risks of inadequate zinc intake.
      SETTING AND DESIGN: National food balance data were obtained for 176 countries
      from the Food and Agriculture Organization of the United Nations. The amount of
      absorbable zinc in these foods was estimated from food composition data, and zinc
      absorption was predicted using a model developed by the International Zinc
      Nutrition Consultative Group (IZiNCG). Demographic data were obtained from United
      Nations estimates, and age- and sex-specific physiological requirements for
      absorbable zinc were estimated using IZiNCG recommendations. RESULTS AND
      CONCLUSIONS: The mean per capita absorbable zinc content of national food
      supplies ranged from 2.98-3.01 mg day(-1) in Western Europe and USA & Canada to
      2.09 mg day(-1) in Southeast Asia. The estimated percentage of individuals at
      risk of inadequate zinc intake ranged from 9.3-9.5% in the regions of North
      Africa & Eastern Mediterranean and USA & Canada to 33.1% in Southeast Asia.
      Overall, approximately 20.5% of the world's population is estimated to be at risk
      of inadequate zinc intake. Data on the absorbable zinc content of national food
      supplies can be used to determine whether further assessments of population zinc
      status and development of intervention programmes are warranted.

PMID- 16277797
TI  - Beneficial effects of short-term nutritional counselling at the primary health
      care level among Brazilian adults.
AB  - OBJECTIVE: To evaluate the impact of a low-cost nutritional intervention in
      changing the lifestyle of adults. DESIGN: Randomised clinical trial. SETTING:
      Primary health-care centre in Sao Jose do Rio Preto, Sao Paulo State, Brazil.
      SUBJECTS: We randomly assigned 104 adults (83 women and 21 men aged 30-65 years,
      body mass index 24-35 kg m(-2), non-diabetic) into two groups: nutrition
      counselling and control. Each subject in the intervention group received three
      individualised nutritional counselling sessions during the first 6 months aimed
      at increasing intakes of fruits, vegetables and olive oil, reducing saturated fat
      and improving physical activity. Body composition, biochemical indicators and
      lifestyle were assessed at baseline and at 6 months and 1 year in both groups.
      RESULTS: After 6 months of follow-up, body weight, waist circumference, diastolic
      blood pressure, fasting blood glucose, total and low-density lipoprotein
      cholesterol, total and saturated fat, and dietary energy and cholesterol levels
      showed a more significant decrease among subjects in the intervention group than
      in the control group (P < 0.05). Moreover, the intervention group showed
      significantly greater improvement in each intervention goal, such as reduced
      intake of saturated fat and increased intakes of fruits, vegetables, fibre and
      olive oil (P < 0.05). After 12 months of follow-up, most of the outcomes were
      maintained. CONCLUSIONS: The low-cost nutritional intervention programme improved
      serum lipids profile and weight control, and appeared to be feasible for use at a
      primary health-care centre in a developing country.

PMID- 16277798
TI  - Efficacy of a community-based dietary intervention to enhance micronutrient
      adequacy of high-phytate maize-based diets of rural Malawian children.
AB  - OBJECTIVE: To evaluate the efficacy of a community-based dietary intervention to
      reduce risk of micronutrient inadequacies in high-phytate maize-based Malawian
      diets. DESIGN: Quasi-experimental post-test design with a non-equivalent control
      group. SETTING: Four villages in Mangochi District, Southern Malawi.
      PARTICIPANTS: Households with children aged 3-7 years in two intervention (n =
      200) and two control (n = 81) villages participated in a 6-month intervention
      employing dietary diversification, changes in food selection patterns, and
      modifications to food processing to reduce the phytate content of maize-based
      diets. Baseline comparability between the groups was confirmed via assessment of
      sociodemographic characteristics, anthropometry, knowledge and practices,
      morbidity, haemoglobin and hair zinc. After 12 months, knowledge and practices
      and dietary intakes were assessed by interactive 24-hour recalls, one during the
      food plenty and a second during the food shortage season. Nutrient adequacy for
      the two groups was compared via dietary quality indicators and predicted
      prevalence of inadequate intakes using the probability approach. RESULTS:
      Intervention children had diets that were significantly more diverse and of a
      higher quality than those of controls. Median daily intakes of protein, calcium,
      zinc (total and available), haem iron, vitamin B12 and animal foods (grams; % of
      total energy) were higher (P < 0.05) whereas phytate intakes, phytate/zinc and
      phytate/iron molar ratios were lower (P < 0.01) in the intervention group; some
      spread of knowledge and practices to controls occurred. CONCLUSIONS: Our
      community-based dietary strategies reduced the predicted prevalence of inadequate
      intakes of protein, calcium, zinc and vitamin B12, but not iron, in children from
      Malawian households with very limited resources.

PMID- 16277799
TI  - Maternal micronutrient status and decreased growth of Zambian infants born during
      and after the maize price increases resulting from the southern African drought
      of 2001-2002.
AB  - OBJECTIVE: To investigate the effects on maternal micronutrient status and infant
      growth of the increased maize prices that resulted from the southern African
      drought of 2001-2002. DESIGN: Longitudinal cohort study. SETTING: A maternal and
      child health clinic in Lusaka, Zambia. SUBJECTS: Maternal and infant health and
      nutrition data and maternal plasma were being collected for a study of breast
      feeding and postpartum health. Samples and data were analysed according to
      whether they were collected before (June to December 2001), during (January 2002
      to April 2003) or after (May 2003 to January 2004) the period of increased maize
      price. Season and maternal HIV status were controlled for in analyses. RESULTS:
      Maize price increases were associated with decreased maternal plasma vitamin A
      during pregnancy (P = 0.028) and vitamin E postpartum (P = 0.042), with the
      lowest values among samples collected after May 2003 (vitamin A: 0.96 micromol l(
      1), 95% confidence interval (CI) 0.84-1.09, n = 38; vitamin E: 30.8 micromol
      mmol(-1) triglycerides, 95% CI 27.2-34.8, n = 64) compared with before January
      2002 (vitamin A: 1.03 micromol l(-1), 95% CI 0.93-1.12, n = 104; vitamin E: 38.9
      micromol mmol(-1) triglycerides, 95% CI 34.5-43.8, n = 47). There were no
      significant effects of sampling date on maternal weight, haemoglobin or acute
      phase proteins and only marginal effects on infant weight. Infant length at 6 and
      16 weeks of age decreased progressively throughout the study (P-values for time
      of data collection were 0.51 at birth, 0.051 at 6 weeks and 0.026 at 16 weeks).
      CONCLUSIONS: The results show modest effects of the maize price increases on
      maternal micronutrient status. The most serious consequence of the price
      increases is likely to be the increased stunting among infants whose mothers
      experienced high maize prices while pregnant. During periods of food shortages it
      might be advisable to provide micronutrient supplements even to those who are
      less food-insecure.

PMID- 16277800
TI  - Nutrition security, livelihoods and HIV/AIDS: implications for research among
      farm worker households in South Africa.
AB  - OBJECTIVE: Previous research on the health transition and nutrition security in
      black South African households revealed the need for further research among farm
      workers who belong to the poorest population categories. This article gives an
      overview of the link between nutrition security, livelihoods and HIV/AIDS in
      South Africa, drawing conclusions for research among farm worker households.
      DESIGN AND SETTING: A literature review, observations on farms and interviews
      with farmers and key informants were carried out in 2003 and 2004. Peer
      examination was done with South African and German researchers from the natural
      and social sciences. RESULTS: Farm workers face poverty and nutrition insecurity
      and continue to be a tragically underserved population group, also in terms of
      research. There is furthermore a lack of in-depth research on underlying causes
      for nutrition security in South Africa and on the link with livelihoods, poverty
      and HIV/AIDS. Micro-social qualitative research from the household and gender
      perspective is required, as valid data on households, their internal dynamics and
      therefore the reflection of social realities are missing. A multidisciplinary
      research approach based on a new conceptual framework was developed to address
      the situation of farm worker households. CONCLUSION: The outlined research
      contributes to existing programmes on farms in the North West Province, with the
      findings being valid also for other parts of southern Africa facing poverty,
      nutrition insecurity and HIV/AIDS.

PMID- 16277801
TI  - Self-administration of a food security scale by adolescents: item functioning,
      socio-economic position and food intakes.
AB  - OBJECTIVE: To evaluate the reliability and validity of a six-item food security
      scale when self-administered by adolescents. DESIGN: Cross-sectional
      questionnaire survey including the six-item food security measure, socio-economic
      variables and a food-frequency questionnaire. SETTING: Representative sample of
      29 schools in Trinidad. SUBJECTS: In total 1903 students aged approximately 16
      years. RESULTS: Item affirmatives ranged from 514 (27%) for the 'balanced meal'
      item to 128 (7%) for the 'skipped or cut meals often' item and 141 (7%) for the
      'hungry' item. Item-score correlations ranged from 0.444 to 0.580. Cronbach's
      alpha was 0.77. Relative item severities from the Rasch model ranged from -1.622
      (standard error 0.043) for the 'balanced meal' item to 1.103 (0.068) for the
      'skipped or cut meals often' item and 0.944 (0.062) for the 'hungry' item. The
      'hungry' item gave a slightly lower relative severity in boys than girls. Food
      insecurity was associated with household overcrowding (adjusted odds ratio
      comparing highest and lowest quartiles 2.61, 95% confidence interval 1.75 to
      3.91), lack of pipe-borne water in the home, low paternal education or paternal
      unemployment. After adjusting for socio-economic variables, food insecurity was
      associated with less frequent consumption of fruit (0.75, 0.60 to 0.94) or fish
      (0.72, 0.58 to 0.88) but more frequent consumption of biscuits or cakes (1.47,
      1.02 to 2.11). CONCLUSIONS: The food security scale provides a valid, reliable
      measure in adolescents, although young people report being hungry but not eating
      relatively more frequently than adults. Food-insecure adolescents have low socio
      economic position and may eat less healthy diets.

PMID- 16277802
TI  - Fruit and vegetable intakes in a sample of pre-school children participating in
      the 'Five for All' project in Bradford.
AB  - BACKGROUND: Longitudinal research has shown that eating fruit and vegetables
      during childhood has a positive impact on long-term health outcome from heart
      disease and asthma. However, recommendations for fruit and vegetable intakes in
      pre-school children are not as explicit as those for adults and few data exist on
      actual intakes of fruit and vegetables in this particular age group. AIMS: To
      describe fruit and vegetable intakes in the daily diets of a sample of pre-school
      children in Bradford, West Yorkshire, and to compare the findings with existing
      national UK data. SUBJECTS: Pre-school children aged 3 and 4 years (n = 207). All
      subjects attended nurseries in the Airedale and Bradford South and West regions
      at the time of the study. DESIGN: Dietary data were collected using the pre
      validated CADET (Child and Diet Evaluation Tool) diary. All children were also
      seen individually in order to assess their awareness and preference for a range
      of fruit and vegetables. RESULTS: Intakes of fruit and vegetables in this sample
      of pre-school children were below recommended levels. Only 16% of children in
      this sample were successfully eating fruit and vegetables on five occasions a day
      and conversely 14% ate no fruit and vegetables at all. Vegetable intakes were far
      lower than fruit intakes with 39% of the sample consuming no vegetables. There
      were statistically significant differences in median fruit and vegetable intakes
      between children with different demographic and lifestyle variables, such as
      which nursery they attended and what the highest educational qualification in the
      household was. Children's awareness of and preferences for different fruit and
      vegetables significantly affected their median intakes of fruit and vegetables.
      CONCLUSION: Fruit and vegetable intakes in this sample of pre-school children
      were far lower than the recommended levels of 5 portions a day. A greater
      diversity of intakes should be encouraged and these data suggest that this may be
      attained by increasing children's awareness by exposing them to a wider range of
      fruit and vegetables.

PMID- 16277803
TI  - Height, age at menarche, body weight and body mass index in life-long
      vegetarians.
AB  - OBJECTIVE: We investigated whether life-long adherence to a vegetarian diet is
      associated with adult height, age at menarche, adult body weight and body mass
      index (BMI), used as indicators of growth, development and obesity, in a large
      sample of adults. DESIGN: This was a cross-sectional study. Anthropometric data
      and information on age, ethnicity, education, age at menarche and age at becoming
      a vegetarian were obtained through a questionnaire. Self-reported height and
      weight were calibrated using predictive equations derived from a previous
      validation study. SETTING: United Kingdom. SUBJECTS: The study includes 45 962
      British men and women aged > or = 20 years of whom 16,083 were vegetarians (not
      eating fish or meat). RESULTS: In men and women, there were no significant
      differences in height, weight or BMI between life-long vegetarians (n = 125 (men)
      and n = 265 (women)) and people who became vegetarian at age > or = 20 years (n =
      3122 (men) and n = 8137 (women)). Nor was there a significant difference in age
      at menarche between life-long vegetarian women and women who became vegetarian at
      age > or = 20 years. CONCLUSION: This study suggests that, compared with people
      who become vegetarian when adult, life-long vegetarians do not differ in adult
      height, weight, BMI or age at menarche in women.

PMID- 16277804
TI  - Past food habit change is related to obesity, lifestyle and socio-economic
      factors in the Malmo Diet and Cancer Cohort.
AB  - OBJECTIVES: To examine if obesity status and socio-economic and lifestyle factors
      are associated with self-reported past food habit change, and also whether the
      level of obesity depends on the reason for change. DESIGN: Cross-sectional
      analysis within the Malmo Diet and Cancer (MDC) study using data from the
      baseline examination and the extensive socio-economic and lifestyle questionnaire
      including questions of past food habit change. The risk of having changed food
      habits in the past was examined using logistic regression. Mean differences in
      obesity status across categories of reasons for past food habit change were
      examined using analysis of variance. SETTING: Malmo, the third largest city in
      Sweden. SUBJECTS: A sub-sample (15 282 women and 9867 men) from the MDC cohort
      recruited from 1992 to 1996. RESULTS: Individuals with body mass index (BMI) >30
      kg m(-2) had an increased risk of having reported past food habit change compared
      with individuals with BMI <25 kg m(-2) (odds ratio (OR) = 1.63, 95% confidence
      interval (CI) = 1.48-1.83 for women; OR = 1.53, 95% CI = 1.32-1.76 for men). The
      highest level of obesity was observed among individuals who had changed their
      diet due to reasons related to the metabolic syndrome. Changers were more likely
      to be highly educated and to live alone, be retired, ex-smokers and non-drinkers
      at baseline. CONCLUSIONS: Because past food habit change is related to obesity
      and other lifestyle and socio-economic factors, a complex confounding situation
      may exist that could seriously influence observed relationships between diet and
      disease. Studies need to collect information on past food habit change and take
      this information into account in the analysis and when interpreting study
      outcomes.

PMID- 16277805
TI  - Environmental and psychosocial correlates of physical activity in Portuguese and
      Belgian adults.
AB  - OBJECTIVES: To investigate differences in reported physical activity levels and
      in perceived environmental and psychosocial correlates of activity between
      Portuguese and Belgian adults; and to analyse the relative contribution of
      environmental and psychosocial variables in explaining physical activity within
      different contexts in Portugal and Belgium. DESIGN: Cross-sectional study.
      SETTING: One city in Portugal (Oeiras) and one in Belgium (Ghent). SUBJECTS: In
      total 526 participants, 247 from Portugal and 279 from Belgium, completed the
      long International Physical Activity Questionnaire and a validated questionnaire
      on environmental and psychosocial correlates. RESULTS: For the sum of all
      activities of at least moderate intensity, a significantly higher mean level of
      activity was found in Belgian adults (P < 0.001). However, comparable percentages
      of the Belgian (38%) and Portuguese (42%) samples did not meet the recommendation
      of 30 min per day. The variance explained by environmental factors was lower (1%
      to 8%) than by psychosocial factors (maximum 42%). Regression analyses showed
      activity-specific relations with environmental variables which were analogous in
      both countries. Walking/cycling for transportation and walking for recreation
      were related to social support from family and/or friends and to walkability and
      walking facilities in the neighbourhood. Recreational physical activity was
      mainly determined by social support, self-efficacy, and perceived benefits and
      barriers. CONCLUSIONS: Activity campaigns addressing psychosocial determinants
      are needed to encourage leisure-time activity, while a combination of
      neighbourhood design changes and encouragement of social support in walking is
      warranted to increase walking in different contexts.

PMID- 16277806
TI  - Physical activity levels in 10- to 11-year-olds: clustering of psychosocial
      correlates.
AB  - OBJECTIVES: To evaluate gender differences for levels of physical activity, for
      sedentary behaviour and for psychosocial correlates in children, to evaluate
      whether psychosocial correlates cluster in meaningful ways and to examine whether
      physical activity and sedentary behaviour differ between children of clusters,
      differentiated by the level of perceived barriers and benefits, attitudes, social
      support and self-efficacy. DESIGN: Cross-sectional study using the Flemish
      Physical Activity Questionnaire. SETTING: Questionnaires to be filled out by the
      children and one of their parents, contacted through the school system. SUBJECTS:
      A sample of 1124 10- to 11-year-olds (579 boys and 545 girls). RESULTS: Girls
      were found to be less active than boys, with boys scoring better for social
      support, perceived benefits and self-efficacy compared with girls. The way of
      clustering differed between boys and girls. Boys were allocated to three
      clusters: one cluster with positive correlates towards physical activity,
      labelled 'positives'; one with negative correlates, labelled 'negatives'; and one
      characterised mainly by high perceived barriers, labelled 'hindered'. In both
      genders the highest levels of physical activity were found in the 'positives',
      the lowest in the 'negatives'. In girls a fourth cluster was identified,
      characterised mainly by low perceived barriers and low social support. Physical
      activity levels in the girls of this cluster, labelled 'indifferents', were the
      second highest. CONCLUSIONS: More research is needed to further characterise
      these clusters. To prevent the physical activity decline during the transition
      from childhood to adulthood, novel interventions need to be explored that focus
      on children of the clusters with the most negative correlates.

PMID- 16277807
TI  - Dietary intakes and health-related behaviours of Korean American women born in
      the USA and Korea: the Multiethnic Cohort Study.
AB  - OBJECTIVE: This study assessed and compared heath-related behaviours and nutrient
      and food group intakes between US-born and Korea-born Korean American women.
      DESIGN AND SUBJECTS: Cross-sectional analyses were performed for ethnic Koreans
      who participated in the Multiethnic Cohort Study in Hawaii and Los Angeles in
      1993-1996. The sample included 492 Korean American women aged 45-75 years who
      were born in the USA (n = 274) or Korea (n = 218). Participants were recruited
      using driver's license files as a primary sampling source and completed a self
      administered questionnaire, including a quantitative food frequency section.
      RESULTS: The proportion overweight or obese was 31.4% in US-born and 9.4% in
      Korea-born women. US-born women had higher intakes of total fat and fat as a
      percentage of energy, and lower intakes of sodium, vitamin C, beta-carotene and
      carbohydrate as a percentage of energy, than Korea-born women. Comparing intakes
      of food group servings from the Food Guide Pyramid, US-born women reported more
      whole grains, red meat and nuts, and less soy products, than did Korea-born
      women. US-born women also consumed fewer vegetables and fruit than those born in
      Korea. Few women in either group reported intakes that met the recommendations
      for dairy foods. Intake of discretionary fat from the Pyramid tip was higher in
      US-born than in Korea-born women. CONCLUSIONS: These findings indicate that the
      acculturation of Korean immigrants affects dietary intakes in ways that may alter
      risks of several chronic diseases. Further studies will be necessary to examine
      the effects of dietary acculturation on disease patterns.

PMID- 16277808
TI  - Glycaemic index, glycaemic load and risk of endometrial cancer: a prospective
      cohort study.
AB  - OBJECTIVE: High-glycaemic-load diets may increase endometrial cancer risk by
      increasing circulating insulin levels and, as a consequence, circulating
      oestrogen levels. Given the paucity of epidemiological data regarding the
      relationship between dietary glycaemic index and glycaemic load and endometrial
      cancer risk, we sought to examine these associations using data from a
      prospective cohort study. DESIGN, SETTING AND SUBJECTS: We examined the
      association between dietary glycaemic load and endometrial cancer risk in a
      cohort of 49,613 Canadian women aged between 40 and 59 years at baseline who
      completed self-administered food-frequency questionnaires between 1982 and 1985.
      Linkages to national mortality and cancer databases yielded data on deaths and
      cancer incidence, with follow-up ending between 1998 and 2000. RESULTS: During a
      mean of 16.4 years of follow-up, we observed 426 incident cases of endometrial
      cancer. Hazard ratios for the highest versus the lowest quartile level of overall
      glycaemic index and glycaemic load were 1.47 (95% confidence interval (CI) = 0.90
      2.41; P for trend = 0.14) and 1.36 (95% CI = 1.01-1.84; P for trend = 0.21),
      respectively. No association was observed between total carbohydrate or total
      sugar consumption and endometrial cancer risk. Among obese women (body mass index
      >30 kg m(-2)) the hazard ratio for the highest versus the lowest quartile level
      of glycaemic load was 1.88 (95% CI = 1.08-3.29; P for trend = 0.54) and there was
      a 55% increased risk for the highest versus the lowest quartile level of
      glycaemic load among premenopausal women. There was also evidence to support a
      positive association between glycaemic load and endometrial cancer risk among
      postmenopausal women who had used hormone replacement therapy. CONCLUSIONS: Our
      data suggest that diets with high glycaemic index or high glycaemic load may be
      associated with endometrial cancer risk overall, and particularly among obese
      women, premenopausal women and postmenopausal women who use hormone replacement
      therapy.

PMID- 16277809
TI  - Validation of the Spanish version of the physical activity questionnaire used in
      the Nurses' Health Study and the Health Professionals' Follow-up Study.
AB  - OBJECTIVE: The objective of this analysis was to test the validity of the
      estimates of energy expenditure and sedentary lifestyle obtained through a self
      administered questionnaire of physical activity for Spanish-speaking people
      adapted from US questionnaires (Nurses' Health Study and Health Professionals'
      Follow-up Study) using a triaxial accelerometer (RT3 Triaxial Research Tracker)
      as the reference. DESIGN AND SETTING: Validation study, calculating the non
      parametric correlation coefficients between the level of physical activity and
      sedentary lifestyle collected by the self-administered questionnaire and the
      triaxial accelerometer measurements. Percentage of misclassification and kappa
      coefficients were also calculated. SUBJECTS: The study population consisted of a
      sample of 40 obese women who were participants of the SUN (Seguimiento
      Universidad de Navarra) project (a prospective cohort study among Spanish
      university alumni). They were selected because of their peculiar metabolic
      characteristics, in the search for a sub-optimal scenario for validity. RESULTS:
      Physical activity during leisure time (estimated as MET-h week(-1)) derived from
      the self-administered questionnaire moderately correlated with kcal day(-1)
      assessed through the accelerometer (Spearman's rho = 0.507, 95% confidence
      interval (CI) 0.232, 0.707). The Spearman correlation between the ratio of
      sedentary lifestyle to physical activity obtained through the questionnaire and
      the direct estimation (RT3) was -0.578 (95% CI -0.754, -0.325). The kappa index
      was 0.25 (P = 0.002) when assessing the cross-classification into quintiles and
      0.41 for the dichotomous estimation of a sedentary lifestyle. Only 2.5% of
      participants were misclassified by the questionnaire more than two quintiles
      apart from the estimates of the RT3. CONCLUSIONS: The moderate values obtained
      for correlation in a sub-optimal scenario for validity and the low percentage of
      extreme misclassification suggest the validity of the questionnaire to assess
      physical activity in Spanish-speaking women aged 20-50 years.

PMID- 16277810
TI  - Examples of 'loaded' terms.

PMID- 16277811
TI  - Human energy requirements. Scientific background papers from the Joint
      FAO/WHO/UNU Expert Consultation. October 17-24, 2001. Rome, Italy.

PMID- 16277812
TI  - Macronutrients as sources of food energy.
AB  - This background paper considers the extent to which the development of new
      recommendations for dietary energy requirements needs to account for the
      macronutrient (fat, carbohydrate, protein and alcohol) profiles of different
      diets. The issues are discussed from the dual perspectives of avoiding under
      nutrition and obesity. It is shown that, in practice, human metabolic processes
      can adapt to a wide range of fuel supply by altering fuel selection. It is
      concluded that, at the metabolic level, only diets with the most extreme
      macronutrient composition would have any consequences by exceeding the natural
      ability to modify fuel selection. However, diets of different macronutrient
      composition and energy density can have profound implications for innate appetite
      regulation and hence overall energy consumption.

PMID- 16277813
TI  - The conceptual framework for estimating food energy requirement.
AB  - OBJECTIVE: In anticipation of the revision of the 1985 Food and Agricultural
      Organization/World Health Organization/United Nations University (FAO/ WHO/UNU)
      Expert Consultation Report on 'Energy and Protein Requirements', recent
      scientific knowledge on the principles underlying the estimation of energy
      requirement is reviewed. DESIGN: This paper carries out a historical review of
      the scientific rationale adopted by previous FAO/WHO technical reports on energy
      requirement, discusses the concepts used in assessing basal metabolic rate (BMR),
      energy expenditure, physical activity level (PAL), and examines current
      controversial areas. Recommendations and areas of future research are presented.
      CONCLUSIONS: The database of the BMR predictive equations developed by the 1985
      FAO/WHO/UNU Expert Consultation Report on Energy and Protein Requirements needs
      updating and expansion, applying strict and transparent selection criteria. The
      existence of an ethnic/tropical factor capable of affecting BMR is not supported
      by the available evidence. The factorial approach for the calculation of energy
      requirement, as set out in the 1985 report, should be retained. The estimate
      should have a normative rather than a prescriptive nature, except for the
      allowance provided for extra physical activity for sedentary populations, and for
      the prevention of non-communicable chronic diseases. The estimate of energy
      requirement of children below the age of 10 years should be made on the basis of
      energy expenditure rather than energy intake. The evidence of the existence of an
      ethnic/tropical factor is conflicting and no plausible mechanism has as yet been
      put forward.

PMID- 16277814
TI  - Energy requirements of infants.
AB  - OBJECTIVE: To estimate the energy requirements of infants from total energy
      expenditure and energy deposition during growth. DESIGN: Energy requirements
      during infancy were estimated from total energy expenditure measured by the
      doubly labelled water method and energy deposition based on measured protein and
      fat gains. SETTING: Database on the total energy expenditure and energy
      deposition of infants was compiled from available studies conducted in China,
      Chile, Gambia, Mexico, The Netherlands, UK, and USA. SUBJECTS: Healthy, term
      infants. RESULTS: Total energy requirements (kJ day(-1)) increased with age and
      were higher in boys than girls due to differences in weight. Energy requirements
      decreased from 473 kJ kg(-1) per day for boys and 447 kJ kg(-1) per day for girls
      at 1 month of age to 337 kJ kg(-1) per day for boys and 341 kJ kg(-1) per day for
      girls at 6 months of age, and thereafter tended to plateau. Energy deposition as
      a percentage of total energy requirements decreased from 40% at 1 month to 3% at
      12 months of age. These estimates are 10-32% lower than the 1985 FAO/WHO/UNU
      recommendations which were based on observed energy intakes of infants.
      CONCLUSIONS: Recommendations for the energy intake of infants should be revised
      based on new estimates of total energy expenditure and energy deposition.

PMID- 16277815
TI  - Energy requirements of children and adolescents.
AB  - Total energy expenditure (TEE) was calculated at 1-18 years of age from
      measurements with doubly labelled water (DLW) in 483 boys and 646 girls, and
      heart rate monitoring (HRM) in 318 boys and 162 girls. Studies on obese,
      underweight and stunted groups were not included. TEE of populations with
      different lifestyles was estimated by factorial calculations in 42 studies on
      time allocation involving 1982 boys and 1969 girls in developed industrialised
      countries, and 1236 boys and 1116 girls in developing countries. Quadratic
      polynomial models were best to predict TEE in boys (TEE(MJ day(-1)) = 1.298 +
      0.265 kg - 0.0011 kg2, r = 0.982, SEE = 0.518) and girls (TEE(MJ day(-1)) = 1.102
      + 0.273 kg - 0.0019 kg2, r = 0.955, SEE = 0.650). TEE at 1-2 years was reduced by
      7% based on DLW measurements and TEE estimates of infants. Energy requirements
      (ER) were calculated adding 8.6 kJ (2 kcal) for each gram of weight gained during
      growth. Compared with the 1985 FAO/WHO/UNU values, ER were 18-20% lower from 1 to
      7 years of age, 12% lower for boys and 5% lower for girls at 7-10 years, and 12%
      higher for either gender from 12 years onwards. Differences between
      industrialised and developing countries, the variance in DLW and HRM studies, and
      the standard error of the estimate (SEE) of the quadratic predictive equations,
      suggested that ER should be adjusted after 5 years of age by +/-15% in
      populations with more or less physical activity than an average lifestyle.
      Physical activity recommendations must accompany dietary recommendations in order
      to maintain optimal health and reduce the risk of diseases associated with
      sedentary lifestyles.

PMID- 16277816
TI  - Energy requirements of adults.
AB  - OBJECTIVES: To describe issues related to energy requirements of free living
      adults and discuss the importance of basal metabolic rate (BMR) and their
      relationships to total energy expenditure (TEE ) and physical activity level
      (PAL, derived as TEE/BMR) and to determine the influence of body weight, height,
      age and sex. DESIGN: Based on a review of the literature, this paper examines the
      variability in BMR due to methodology, ethnicity, migration and adaptation (both
      metabolic and behavioural) due to changes in nutritional status. Collates and
      compiles data on measurements of TEE in free living healthy adults, to arrive at
      limits and to compare TEE of populations with different life-styles. RESULTS AND
      CONCLUSIONS: The constancy of BMR and its validity as a reliable predictor of TEE
      in adults as well as the validity of PAL as an index of TEE adjusted for BMR and
      thus its use to categorise the physical activity pattern and lifestyle of an
      individual was confirmed. The limits of human daily energy expenditure at around
      1.2 x BMR and 4.5 x BMR based on measurements made in free living adults have
      been reported in the literature. A large and robust database now exists of energy
      expenditure measurements obtained by the doubly labelled water method in the
      scientific literature and the data shows that, in general, levels of energy
      expenditure are similar to the recommendations for energy requirements adopted by
      FAO/WHO/UNU (1985). The review also confirms that metabolic adaptation to energy
      restriction is not an important factor that needs to be considered when
      recommending energy requirements for adults in developing countries.

PMID- 16277817
TI  - Energy requirements during pregnancy and lactation.
AB  - OBJECTIVE: To estimate the energy requirements of pregnant and lactating women
      consistent with optimal pregnancy outcome and adequate milk production. DESIGN:
      Total energy cost of pregnancy was estimated using the factorial approach from
      pregnancy-induced increments in basal metabolic rate measured by respiratory
      calorimetry or from increments in total energy expenditure measured by the doubly
      labelled water method, plus energy deposition attributed to protein and fat
      accretion during pregnancy. SETTING: Database on changes in basal metabolic rate
      and total energy expenditure during pregnancy, and increments in protein based on
      measurements of total body potassium, and fat derived from multi-compartment body
      composition models was compiled. Energy requirements during lactation were
      derived from rates of milk production, energy density of human milk, and energy
      mobilisation from tissues. SUBJECTS: Healthy pregnant and lactating women.
      RESULTS: The estimated total cost of pregnancy for women with a mean gestational
      weight gain of 12.0 kg, was 321 or 325 MJ, distributed as 375, 1200, 1950 kJ day(
      1), for the first, second and third trimesters, respectively. For exclusive
      breastfeeding, the energy cost of lactation was 2.62 MJ day(-1) based on a mean
      milk production of 749 g day(-1), energy density of milk of 2.8 kJ g(-1), and
      energetic efficiency of 0.80. In well-nourished women, this may be subsidised by
      energy mobilisation from tissues on the order of 0.72 MJ day(-1), resulting in a
      net increment of 1.9 MJ day(-1) over non-pregnant, non-lactating energy
      requirements. CONCLUSIONS: Recommendations for energy intake of pregnant and
      lactating women should be updated based on recently available data.

PMID- 16277818
TI  - Energy requirements and aging.
AB  - OBJECTIVE: To summarise the literature on energy requirements and aging. DESIGN:
      An analysis and review of published data on components of energy expenditure and
      total energy expenditure (TEE). SETTING: Data on basal metabolic rate (BMR) and
      TEE were obtained from the US Institute of Medicine of the National Academies
      database (all available data from studies published before 2001, collected from
      20 researchers willing to provide individual subject results). SUBJECTS: Those
      individuals from the database who were 20-100 years of age. RESULTS: TEE and
      physical activity level (PAL, defined as the ratio of total to resting energy
      expenditure) declined progressively throughout adult life in both normal weight
      and overweight men and women. In normal weight individuals (defined as body mass
      index (BMI) 18.5-25.0 kg m(-2)) TEE fell by approximately 150 kcal per decade,
      and PAL fell from an average of 1.75 in the second decade of life to 1.28 in the
      ninth decade. Thermic effect of feeding data from other published studies
      indicated no consistent change associated with aging. CONCLUSIONS: Aging is
      associated with progressive declines in resting and TEE, which have implications
      for defining dietary energy requirements at different stages of adult life.

PMID- 16277819
TI  - Insights into energy requirements in disease.
AB  - Accurate information about the energy needs of a range of acute and chronic
      diseases and morbidity is lacking and often complicated by the medication
      prescribed to treat the condition and also because of the presence of pre
      existing malnutrition. Assessing the energy requirements of patients with acute
      and chronic diseases is more complex than for those in good health. These
      requirements not only depend on the aggressiveness of the disease and level of
      inactivity it causes, but also on the treatment, and the presence of prior
      malnutrition. It used to be generally believed that the energy requirements were
      increased in a number of diseases. It is now realised that this is not usually
      the case. Therefore, it is necessary to put these changing ideas into context by
      considering a wide range of acute and chronic diseases which this paper proposes
      to do. This paper is almost exclusively restricted to studies that have measured
      total energy expenditure (TEE) using tracer techniques in both hospital and the
      community (mostly doubly labelled water and to a lesser extent bicarbonate-urea),
      and continuous 24-hour indirect calorimetry in artificially ventilated patients
      in hospital.

PMID- 16277820
TI  - Consequences of inadequate food energy and negative energy balance in humans.
AB  - Energy deficiency is probably best measured in adults by the body mass index
      (BMI). Acute energy deficiency (AED) is associated with body weight loss, along
      with changes in body composition, as well as a reduced BMR and physical activity.
      Chronic energy deficiency (CED) is an inadequacy in food to which individuals
      adapt, at some cost. Individuals with this have never 'lost' weight: they have
      simply grown less. They adapt to the decreased food energy by reductions in their
      total energy expenditure (TEE), linked mainly to a lower body size, and to their
      physical activity. It seems unlikely that enhanced metabolic efficiency
      contributes substantially to energy saving in CED. Supplementation of energy
      deficient individuals is accompanied by significant fat deposition; this may have
      deleterious consequences. Women in many developing countries achieve a successful
      outcome to pregnancy in spite of being chronically undernourished. Reductions in
      basal metabolism and behavioural changes in the form of diminished physical
      activity could meet most of the extra energy needed for pregnancy. Milk energy
      output is maintained within the expected range in undernourished lactating
      mothers. Energy deficiency in children is best measured by height-for-age for
      stunting, and weight-for-height for wasting. Deficits in behavioural and
      functional parameters in children exist with undernutrition, and can be reduced
      by early nutritional supplementation along with the appropriate environment.

PMID- 16277821
TI  - Consequences of food energy excess and positive energy balance.
AB  - This paper discusses possible consequences of energy excess throughout the life
      cycle. Firstly we consider the effects of foods on hunger, satiety and satiation.
      Also, the changes in food availability and consumption in relation to changes in
      social and economic determinants of energy excess. The relationship between
      physical activity and energy intake (EI) is also considered. Secondly we explore
      the definition of energy excess and the metabolic effects of macronutrients
      (mainly in relation to fuel partitioning oxidation/storage) on energy balance.
      The cellular and molecular regulation determined by specific genes involved in
      lipogenesis, fuel partitioning and/or in energy dissipation are explored.
      Thirdly, we examine the main consequences induced by energy excess and positive
      energy balance, starting with the alterations in glucose utilisation (insulin
      resistance) leading to type 2 diabetes and the linkage of energy excess with
      other non-communicable diseases (NCDs). Biological, social and psychological
      consequences during perinatal, childhood and adolescence periods are specifically
      analysed. Fourthly, the transition from energy deficit to excess, under the optic
      of a developing country is analysed with country examples drawn from Latin
      America. The possible role of supplementary food programmes in determining
      positive energy balance is discussed especially in relation to pre-school and
      school feeding programmes. Fifthly, we deal with the economic costs of energy
      excess and obesity related diseases. Finally, some areas where further research
      is needed are described; biological and genetic determinants of individual and
      population energy requirements, foods and food preparations as actually consumed,
      consumer education and research needs on social determinants of energy
      imbalances.

PMID- 16277822
TI  - Dietary intake measurements.
AB  - OBJECTIVE: To provide a concise summary of field and laboratory methods for the
      measurement of dietary intake with particular reference to the assessment of
      energy and protein intake and to the pitfalls and difficulties that may be
      encountered in practice when implementing the methods both in the field and under
      laboratory conditions.

PMID- 16277823
TI  - Laboratory and field measurements of body composition.
AB  - OBJECTIVE: This background paper was prepared in response to a request to review
      the concepts related to measurement of body composition, to discuss laboratory
      and field methods of assessing body composition and to discuss the practical
      applications of the methods--how they might be used singly or in combination to
      provide data for a selected population. DESIGN: The common laboratory and field
      methods are described and discussed, with particular attention to the assumptions
      involved and the applicability of the methods to the different population groups.
      Most measurements of body composition are made in the field, at the bedside or
      clinic as opposed to in the laboratory. The laboratory methods have a role to
      play in their own right, in research into new concepts, models and methods.
      However, they are particularly important in establishing the accuracy of the
      field methods. SETTING: Field, bedside and laboratory studies. SUBJECTS:
      Children, adults, the elderly, ethnic groups. RESULTS: Laboratory estimates of
      body compositions are best performed by multi-component methods or by 2-component
      methods adjusted for to the populations under investigation. There is a scarcity
      of data for most of the populations in the world. CONCLUSIONS: Energy
      requirements based on body weight are an approximation since they do not take
      into account differences in body composition, which will better determine the
      true requirements. The measurement of body composition occurs in many branches of
      biology and medicine. It is used in the assessment of nutritional and growth
      status and in disease states and their treatment. Energy stores, skeletal muscle
      and protein content can be determined and changes monitored. In human energetics,
      body composition is widely used for the standardisation of other variables, such
      as basal metabolic rate (BMR), in the assessments of ethnic and environmental
      differences and of variability and adaptation to different levels of nutrition.
      Choosing a method is very problematic. Users want simple, inexpensive, rapid,
      safe accurate methods to measure body composition but speed and simplicity come
      at the expense of accuracy. Recommendations are made for age, sex, and in some
      cases, fatness and ethnic specific methods.

PMID- 16277824
TI  - Measurement of energy expenditure.
AB  - Measurement of energy expenditure in humans is required to assess metabolic
      needs, fuel utilisation, and the relative thermic effect of different food,
      drink, drug and emotional components. Indirect and direct calorimetric and non
      calorimetric methods for measuring energy expenditure are reviewed, and their
      relative value for measurement in the laboratory and field settings is assessed.
      Where high accuracy is required and sufficient resources are available, an open
      circuit indirect calorimeter can be used. Open-circuit indirect calorimeters can
      employ a mask, hood, canopy or room/chamber for collection of expired air. For
      short-term measurements, mask, hood or canopy systems suffice. Chamber-based
      systems are more accurate for the long-term measurement of specified activity
      patterns but behaviour constraints mean they do not reflect real life. Where
      resources are limited and/or optimum precision can be sacrificed, flexible total
      collection systems and non-calorimetric methods are potentially useful if the
      limitations of these methods are appreciated. The use of the stable isotope
      technique, doubly labelled water, enables total daily energy expenditure to be
      measured accurately in free-living subjects. The factorial method for combining
      activity logs and data on the energy costs of activities can also provide
      detailed information on free-living subjects.

PMID- 16277825
TI  - Basal metabolic rate studies in humans: measurement and development of new
      equations.
AB  - OBJECTIVE: To facilitate the Food and Agriculture Organization/World Health
      Organization/United Nations University Joint (FAO/WHO/UNU) Expert Consultation on
      Energy and Protein Requirements which met in Rome in 1981, Schofield et al.
      reviewed the literature and produced predictive equations for both sexes for the
      following ages: 0-3, 3-10, 10-18, 18-30, 30-60 and >60 years. These formed the
      basis for the equations used in 1985 FAO/WHO/UNU document, Energy and Protein
      Requirements. While Schofield's analysis has served a significant role in re
      establishing the importance of using basal metabolic rate (BMR) to predict human
      energy requirements, recent workers have subsequently queried the universal
      validity and application of these equations. A survey of the most recent studies
      (1980-2000) in BMR suggests that in most cases the current FAO/WHO/UNU predictive
      equations overestimate BMR in many communities. The FAO/WHO/UNU equations to
      predict BMR were developed using a database that contained a disproportionate
      number--3388 out of 7173 (47%)--of Italian subjects. The Schofield database
      contained relatively few subjects from the tropical region. The objective here is
      to review the historical development in the measurement and application of BMR
      and to critically review the Schofield et al. BMR database presenting a series of
      new equations to predict BMR. DESIGN: This division, while arbitrary, will enable
      readers who wish to omit the historical review of BMR to concentrate on the
      evolution of the new BMR equations. SETTING: BMR data collected from published
      and measured values. SUBJECTS: A series of new equations (Oxford equations) have
      been developed using a data set of 10,552 BMR values that (1) excluded all the
      Italian subjects and (2) included a much larger number (4018) of people from the
      tropics. RESULTS: In general, the Oxford equations tend to produce lower BMR
      values than the current FAO/WHO/UNU equations in 18-30 and 30-60 year old males
      and in all females over 18 years of age. CONCLUSIONS: This is an opportune moment
      to re-examine the role and place of BMR measurements in estimating total energy
      requirements today. The Oxford equations' future use and application will surely
      depend on their ability to predict more accurately the BMR in contemporary
      populations.

PMID- 16277826
TI  - A compilation of energy costs of physical activities.
AB  - OBJECTIVES: There were two objectives: first, to review the existing data on
      energy costs of specified activities in the light of the recommendations made by
      the Joint Food and Agriculture Organization/World Health Organization/United
      Nations University (FAO/WHO/UNU) Expert Consultation of 1985. Second, to compile
      existing data on the energy costs of physical activities for an updated annexure
      of the current Expert Consultation on Energy and Protein Requirements. DESIGN:
      Electronic and manual search of the literature (predominantly English) to obtain
      published data on the energy costs of physical activities. The majority of the
      data prior to 1955 were obtained using an earlier compilation of Passmore and
      Durnin. Energy costs were expressed as physical activity ratio (PAR); the energy
      cost of the activity divided by either the measured or predicted basal metabolic
      rate (BMR). RESULTS: The compilation provides PARs for an expanded range of
      activities that include general personal activities, transport, domestic chores,
      occupational activities, sports and other recreational activities for men and
      women, separately, where available. The present compilation is largely in
      agreement with the 1985 compilation, for activities that are common to both
      compilations. CONCLUSIONS: The present compilation has been based on the need to
      provide data on adults for a wide spectrum of human activity. There are, however,
      lacunae in the available data for many activities, between genders, across age
      groups and in various physiological states.

PMID- 16277827
TI  - Estimating energy requirements: regression based prediction equations or
      multiples of resting metabolic rate.
AB  - Energy requirements have traditionally been determined based on multiples of
      resting metabolic rate (RMR), known as Physical Activity Levels (PAL). With more
      data from doubly labelled water studies alternative approaches for estimating
      energy requirements have been suggested. Statistical analysis reveals that body
      weight explains more of the variance in total energy expenditure (TEE) than does
      RMR. The explanation for this phenomenon is that body weight contributes to the
      variance of both RMR and the other major determinant of TEE, i.e. physical
      activity related energy expenditure. Thus, in effect, the regression-based
      approach provides a more physiological appropriate model for TEE. Its major
      departure from tradition, difference from current adult proposals, and time taken
      for acceptance are the disadvantages of the regression-based approach.

PMID- 16277828
TI  - Effect of infection on energy requirements of infants and children.
AB  - This is a brief review of the effects of infection and other forms of stress on
      the energy needs of infants and young children. The results of studies estimating
      energy expenditure in infants and young children during illness and convalescence
      were evaluated. Expectations that energy expenditure is influenced by the
      severity of illness, nutritional status, the nature of the illness, the presence
      and intensity of 'catch-up growth,' and the stage of convalescence are generally
      supported by the literature. The qualitative or quantitative nature of responses,
      however, are not uniform for diverse illnesses in children in diverse planes of
      nutritional adequacy.

PMID- 16277829
TI  - Review of the evidence linking protein and energy to mental development.
AB  - OBJECTIVE: To examine the evidence as to whether the relationship between
      undernutrition and poor child development is causal. DESIGN: Selected studies
      from developing countries were discussed. Observational studies were first
      considered then experimental studies of preventative and remedial
      supplementation. The type of functions affected, the presence of sensitive
      periods and the role of protein and energy versus that of micronutrients were
      reviewed. RESULTS: Childhood undernutrition is generally associated with
      concurrent and longer term deficits in cognition, behaviour and motor skills,
      although the relationship is likely to be confounded by socio-economic factors.
      Supplementation trials have had many design problems. However, those beginning at
      any age from pregnancy up to 24 months have consistently had concurrent benefits
      suggesting a causal relationship. Supplement begun in older children had little
      or no effect, albeit there are too few studies to conclude with confidence. The
      limited evidence suggests that benefits are more likely to be sustained if
      supplementation begins in late pregnancy or at birth and is continued until the
      child is at least 24 months old. Deficits in cognition tend to be global and
      there is insufficient evidence of specific deficits. There is some evidence that
      the first 2 years of life are most sensitive to the effects of undernutrition.
      Most studies have failed to separate the effects of energy and protein from those
      of micronutrients. One study showed that energy and/or protein affects children's
      development. Psychosocial stimulation has had consistent benefits on
      undernourished children's development. CONCLUSIONS: Public health nutrition
      programmes should include a component in which children who are at risk are
      targeted during the first 2 years of life with combined interventions involving
      nutrition, health care and early stimulation.

PMID- 16277830
TI  - The Oxford Brookes basal metabolic rate database--a reanalysis.
AB  - OBJECTIVE: To produce prediction equations for basal metabolic rate (BMR) derived
      from weight and height covering the age range from birth to old age. DESIGN:
      Cross-sectional data on BMR, sex, age, weight, height, ethnicity and measurement
      technique from the Oxford Brookes BMR database. SETTING: Worldwide. SUBJECTS:
      Data for 13,910 men, women and children from 174 papers published between 1914
      and 2001. RESULTS: Absolute and proportional regression models were developed for
      each sex, showing a steep rise in predicted BMR with age until 15 years, more
      pronounced in males than females, then a gradual fall through adulthood.
      Predicted BMR increased by 6% and 1.4%, respectively, per standard deviation
      increase in weight and height. Predicted BMR in Caucasians was 4% higher than in
      non-Caucasians, though the effect size was sensitive to the inclusion or
      exclusion of data from certain influential publications. The effect of
      measurement technique on BMR, closed-circuit versus open-circuit, was small, near
      1%. CONCLUSIONS: It is possible to develop prediction equations that avoid
      splitting the data into arbitrary age groups. Heterogeneity between publications
      is greater than might be expected by chance, probably due to undocumented
      differences in technique.

PMID- 16277831
TI  - Validation of three predictive equations for basal metabolic rate in adults.
AB  - OBJECTIVE: To cross-validate three predictive set of equations for basal
      metabolic rate (BMR) developed by Schofield (Schofield database), Henry (Oxford
      database) and Cole (Oxford database) using mean values for age, weight, height
      and BMR of published studies. DESIGN: Literature review of studies published from
      1985 to March 2002. SETTING: All studies selected used appropriate methods and
      followed conditions that met the criteria established for basal metabolism, were
      performed in healthy adults, and were not part of the Schofield or Oxford
      database. SUBJECTS: A total of 261 groups of men and women from 175 studies were
      selected and categorised in three age groups (18.5-29.9, 30.0-59.9, > or = 60
      years old) and three body mass index (BMI) groups (normal weight, overweight and
      obese). RESULTS: Linear regression and concordance correlation analysis showed
      that the three sets of equations had the same association and agreement with
      measured BMR, across gender, age, and BMI groups. The agreement of all equations
      was moderate for men and poor for women. The lowest mean squared prediction
      errors (MSPRs) were given by Henry equations in men and Cole equations in women.
      Henry and Cole equations gave lower values than Schofield equations, except for
      men over 60 years of age. Henry equations were the most accurate in men. None of
      the three equations performed consistently better in women. CONCLUSION: These
      results support the use of Henry equations in men with a wide range of age and
      BMI. None of the proposed predictive equations seem to be appropriate to estimate
      BMR in women.

PMID- 16277832
TI  - [Adjunctive reflections on history of hematopoietic stem cell study--editorial].
AB  - The article reviews concisely around the history of hematopoietic stem cell
      research, basic and clinical, since its very beginning after the nuclear
      explosions at the end of the Second World War, that explains why the stem cell
      study in the world began with the hematopoietic stem cells and the existence of
      non-hematopoietic stem cell in vivo had been left out of account for many decades
      till 21st century. During 50-60s of the last century, it was known from the
      animal experiments that there must be hematopoietic stem cells existing in vivo
      and believed that the effective bone marrow transplant is actually the stem cell
      transplantation. It is reviewed how the basic studies of stem cell interacted
      with the clinical stem cell transplantation and how great the contribution was
      given to strongly push forward the development of contemporary stem cell biology
      and modern hematology from the basic studies especially in the immunological and
      molecular biological fields, for instance, the applications of HLA technology and
      monoclonal antibody produced, flow cytometry, and genetic recombinant cytokines,
      the novel technique for gene cloning, genomics, proteomics, and iRNA as well as
      bioinformatics. It has lead to the pluralistic cell therapy as a novel trend in
      stem cell transplantation as to combine immunotherapy and mesenchymal stem cells
      with the conventional stem cell transplants. This paper looks back in the past
      several decades, however, on every achievement of stem cell study that were
      usually accompanied with some idealistic one-sidedness or even errors in design
      and conclusion of some experiments. Usually it took a period of 2 or even 4
      decades to clarify some basic idea, that seemed normal in the science
      development, for examples, the dividing line between the hematopoietic stem cell
      and progenitor cells, possibility to expand or clone the real stem cell ex vivo,
      and whether the majority of leukemias are originated from stem cell level, etc.
      Towards the end of 20th century, the greatest discovery was the existence of
      adult stem cells in adult tissues, which are no doubt the remnants from the
      embryonic development including all stages of embryonic stem cells, very earlier
      and later, hematopoietic and nonhematopoietic, and could be induced to
      differentiate into all kinds of tissue cells by proper ways in vitro. No evidence
      has really provided for the hypothesis of so called trans-differentiation or de
      differentiation, which brought about strong calls in questions in the past 5
      years. The problems in developing the clinical gene therapy by using
      hematopoietic stem cell as carrier of interested gene still remained to be solved
      so far. Because of the relatively weak base of related basic studies, the
      clinical application of gene therapy resulted in the failure of clinical practice
      with lots of lessons towards the end of last century. The whole history of stem
      cell study in the world was an endless process of continuous redress for
      theoretical ideas in stem cell biology that had never been consummate.

PMID- 16277833
TI  - Characteristics and prognostic factors of acute myeloid leukemia with t (8; 21)
      (q22; q22).
AB  - The translocation t (8; 21) (q22; q22) frequently associated with additional
      chromosomal aberrations is one of the most recurrent chromosomal abnormalities in
      AML. Clinically, this type of AML usually shows some specific characteristics and
      has a good response to chemotherapy with a high remission rate and a relatively
      long median survival. On the other hand, some reports also showed poor prognosis
      in AML patients with t (8; 21), and the associated bad-prognosis factors have not
      been strongly established to date. To investigate this issue and to further
      identify the related characteristics of t (8; 21) AML in China, 75 Chinese AML
      patients with t (8; 21) were retrospectively analyzed. They comprised 68 cases of
      M(2), five of M(4) and two of M(5) according to FAB classification. The results
      indicated that Auer rods were observed in 39 patients (52%) and marrow
      eosinophilia was detected in only 5 patients (6.7%). These patients showed high
      level of HLA-DR and CD34 expression, while CD19 was detected in only 13 patients
      (20.9%). Cytogenetically, 62.5% cases had additional chromosomal abnormalities,
      and the main associated recurrent additional abnormalities were loss of a sex
      chromosome (LOS), trisomy 4, del (9q) and trisomy 8. After conventional induction
      therapy, 62 patients attained complete remission (CR) resulting in the CR rate
      82.7%. With a follow-up of 1 to 96 months, 19 cases relapsed at a median time of
      10.5 months (range 3 to 42 months). The median overall survival was 20 months,
      and the estimated 5-year overall survival (OS) rate was 32.3%. In multivariate
      analyses of prognostic factors, karyotype, extramedullary leukemia, age and post
      remission therapy were of prognostic value for OS. Patients with additional
      chromosomal anomalies had shorter survival compared to those with t (8; 21) only
      (P = 0.019), no matter which kind of additional karyotype it was. Extramedullary
      leukemia was an adverse prognostic factor (P = 0.012). Patients aged 15 years or
      less had a longer survival than those aged more than 15 years (P = 0.045).
      Patients accepted HSCT in post-remission therapy had better outcome compared to
      those with chemotherapy only. It is concluded that Chinese AML patients with t
      (8; 21) had some different characteristics as compared with patients from other
      countries, a relatively poor outcome was observed in our patients, especially in
      those with extramedullary leukemia or additional chromosomal abnormalities. HSCT
      should be recommended to t (8; 21) AML in China, especially to those with adverse
      prognostic factors.

PMID- 16277834
TI  - [Expression and significance of melanoma antigen gene-3 in endoplasmic reticulum
      stress-induced apoptosis of K562 cells].
AB  - This study was aimed to explore the expression and significance of melanoma
      antigen gene-3 (MAGE-3) in endoplasmic reticulum stress-induced apoptosis. After
      the treatment of leukemia cell line K562 and its multidrug-resistant cell line
      K562/A02 by thapsigargin, intracellular calcium concentrations ([Ca(2+)]i) in
      K562 and K562/A02 were measured by fluorescence spectrophotometer with calcium
      sensitive fluorescence indicator Fura-2/AM; expression changes of glucose
      regulated protein 78 (GRP78) were detected by Western blot; morphological change
      of apoptotic cell was investigated by AO/EB fluorescent staining under
      fluorescent microscope; apoptosis rate was determined by terminal
      deoxyribonucleotidyl transferase (TdT)-mediated dUTP nick end labelling (TUNEL)
      staining; the expression of MAGE-3 gene mRNA was detected by RT-PCR. The results
      showed that (1) thapsigargin induced the enhancement of [Ca(2+)]i with different
      extent in K562 and K562/A02 cells, and the enhancement of [Ca(2+)]i was dose
      dependent in experiment range. At the same time, thapsigargin induced
      upregulation of GRP78 protein expression and typical apoptotic changes of K562
      and K562/A02 cells, apoptotic rate was also dose-dependent in experiment range.
      The [Ca(2+)]i in K562/A02 cells were higher than that in K562 cells. (2) in the
      course of endoplasmic reticulum stress-induced apoptosis by thapsigargin, the
      expression of MAGE-3 gene mRNA was remarkably downregulated. Moreover, the
      expression of MAGE-3 gene mRNA in K562/A02 cells was higher than that in K562
      cells. It is concluded that (1) thapsigargin induces endoplasmic reticulum stress
      induced apoptosis of K562 and K562/A02 cells in experiment range, and this may be
      associated with downregulation of MAGE-3 mRNA expression or MAGE-3 gene may
      participates in the regulation of endoplasmic reticulum stress-induced apoptosis.
      (2) MAGE-3 gene may possess anti-apoptotic activity, multidrug resistance in
      K562/A02 cells can be associated with [Ca(2+)]i increase and upregulation of MAGE
      3 expression.

PMID- 16277835
TI  - [Gene expression profile in K562 cells treated by interferon alpha].
AB  - To study the gene expression profile in K562 cells treated by IFN-alpha, so as to
      provide some information about the potential mechanism of IFN-alpha curing CML,
      the changes of gene expression were examined with the DNA array in K562 cells
      before and after treatment with IFN-alpha. The results showed that no gene
      expression difference more than 2.5 times in K562 cells was found on the first
      day after treatment with IFN-alpha (200 U/ml), then the genes significant
      expression difference increased step by step, and reached the peak on the forth
      day. In all examined genes, 97 genes significant expression difference were
      detected, 86.60% (84/97) gene of interest out of those gene were up-regulated,
      13.40% (13/97) were down-regulated. In these 97 genes with significant expression
      difference, cell regulator protein genes accounted to 23.71% (23/97), surface
      receptor genes 14.43% (14/97), oncogenes and tumor suppressors 11.34% (11/97),
      extracellular communication proteins 9.28% (9/97), cell adhesion molecular genes
      8.25% (8/97) and the other genes accounted to 32.99% (32/97). JAK1 was up
      regulated to 3.78 times, JAK2 to 15.43, STAT1 and STAT2 were up-regulated to
      11.98 and 8.11 times respectively, and these genes are components of JAK-STAT
      pathway. The number of different genes began to decrease on the fifth day. There
      were still 9 genes that had expression difference more than 3 times on the twenty
      first day. It is concluded that when concentration of IFN-alpha was 200 U/ml, the
      forth day should be considered as the best time to examine change of gene
      expression in K562 cells treated by IFN-alpha. IFN-alpha realizes its biological
      functions through the JAK-STAT pathways and it may be one of the mechanisms for
      curing CML with IFN-alpha.

PMID- 16277836
TI  - Expressions of cyclin B1 and p21cipl in adult acute leukemia and their
      correlation.
AB  - Cyclin B1, a positive regulator, controls mitosis occurrence, plays an important
      role in cell proliferation. To investigate the clinical significance of cyclin
      B1, the expression of cyclin B1 in acute leukemia (AL) patients was measured; the
      expression of cyclin B1 and p21(cipl), and their cell cycle distribution were
      assayed by flow cytometry in 136 adult patients with newly diagnosed AL, 10
      continuous complete remission (CCR) AL and 17 normal controls; the mRNA of cyclin
      B1 and p21(cipl), and the proliferation cell nuclear antigen (PCNA) in patients
      and normal controls were detected with semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR). The results showed that the expression of
      cyclin B1 in newly diagnosed AL patients was significantly higher than that in
      normal controls. For the relapsed AL patients, the cyclin B1 expression was also
      higher than that in normal controls, but lower than that in newly diagnosed
      cases, there was no significant difference between the remission cases and normal
      controls, nor difference between CCR AL patients and normal controls. All
      patients with high cyclin B1 expression had an unscheduled expression manner,
      that cyclin B1 protein appeared in G(1) phase, and in some case it even higher
      than that of G(2) phase. The response rate (partial remission + complete
      remission) and survival rate in the cyclin B1 high expressed patients were higher
      than that of cyclin B1 low expressed patients. The relapse rate in cyclin B1 high
      expressed patients was higher than that in cyclin B1 normally expressed patients.
      The survival rate in cyclin B1 high expressed patients was higher than that in
      cyclin B1 low expression patients. A negative correlation between the expression
      of cyclin B1 and p21(cipl) was observed. Additionally, cyclin B1 protein
      expression was generally correlated with proliferation index (PI) and
      proliferation cell nuclear antigen (PCNA). It is concluded that this study
      demonstrates for the first time cyclin B1 overexpression and abnormally
      distribution in cell cyclin of newly diagnosed AL patients. It was considered
      that cyclin B1 may play an important role in leukemic pathogeneses and can be one
      of the factors influencing the prognosis of AL patients.

PMID- 16277837
TI  - [Apoptosis mechanism in human chronic myelogenous leukemia K562 cells induced by
      tetra-arsenic tetra-sulfide].
AB  - To explore the effects of tetra-arsenic tetra-sulfide (As(4)S(4)) in treatment of
      human chronic myelogenous leukemia K562 cells and its mechanism, trypan blue
      staining and microculture MTS assay were used to measure the effects of As(4)S(4)
      on growth inhibition of K562 cells; the morphologic change was determined by
      Wright's staining assay. The apoptosis rate and cell cycle were detected by flow
      cytometry; the changes of transcript and protein level were determined by real
      time quantitative RT-PCR and Western blot analysis, respectively. The results
      indicated that As(4)S(4) had significant cytotoxicity on K562 cells. At the
      concentration of 0.5 micromol/L, the cell viability decreased significantly after
      being cultured with As(4)S(4) for 24 hours. When the concentration was lower than
      0.1 micromol/L, As(4)S(4) had a little effect on K562 cells. The effect of
      As(4)S(4) on K562 was time- and concentration- dependent. After being cultured
      with As(4)S(4) at the concentration of 1.0 micromol/L for 24 to 48 hours, K562
      cells displayed typical morphological changes of apoptosis. At a concentration
      greater than or equal to 1.0 micromol/L, As(4)S(4) could induce apoptosis
      significantly. After 12 hours of incubation with 1.0 micromol/L As(4)S(4), the
      apoptosis rate increased from (3.47 +/- 0.42)% to (6.16 +/- 0.98%). At the same
      time, the percentage of cells in G(1) phase decreased from (69.65 +/- 3.24)% to
      (50.53 +/- 2.86)%, whereas the percentage of cells in G(2)/M phase increased from
      (9.56 +/- 2.51)% to (12.91 +/- 2.13)%. The mRNA level of Bcl-X(L) and the protein
      level of pAkt were down-regulated after the inhibition of As(4)S(4), while the
      mRNA expression of Bcl-2, Bad and Bax had no change. Both of the transcript and
      protein level of bcr-abl had no change after incubation with As(4)S(4). It is
      concluded that As(4)S(4) can inhibit the growth of K562 cells efficiently through
      inducing apoptosis and cell cycle arrest. It seems that As(4)S(4) interferes with
      pAkt pathway and down-regulates Bcl-X(L), which may be involved in the response
      of K562 to this agent.

PMID- 16277838
TI  - [Arsenic trioxide induced leukemic cell apoptosis relative to NF-kappaB
      activation].
AB  - To investigate the relationship of As(2)O(3)-induced leukemic cell apoptosis with
      NF-kappaB activation and expression of VEGF, MMP9, apoptosis of K562-n cells
      induced by As(2)O(3) was analyzed by Annexin V, the dynamic changes of NF-kappaB,
      MMP9 and VEGF expressions were detected by immunohistochemistry. The results
      showed that activity of NF-kappaB could be increased, accompanied by higher level
      of expression of MMP9 and VEGF when apoptosis of K562-n cells was induced by
      As(2)O(3). Dexamethasome not only increased significantly the apoptotic rate, but
      also suppressed the activation of NF-kappaB of K562-n cells induced by As(2)O(3).
      Furthermore, there was a positive correlation between the expression of MMP9,
      VEGF and the activity of NF-kappaB. It is concluded that As(2)O(3) can induce
      apoptosis, in the meanwhile, activate NF-kappaB and up-regulate expression of
      MMP9 and VEGF in K562-n cell line. The mechanism of apoptosis of K562-n cells
      enhanced by dexamethasome may be related to suppression of the activation of NF
      kappaB and expression of MMP9 and VEGF.

PMID- 16277839
TI  - [Mechanism of apoptosis induced by indole-3-acetic acids combined with
      horseradish peroxidase in leukemia cell line K562].
AB  - To investigate the possible mechanism of apoptosis induced by indole-3-acetic
      acid (IAA) combined with horseradish peroxidase in leukemia cell line K562, cell
      proliferation and apoptosis of K562 cell were examined by MTT assay and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL),
      respectively; the activity of superoxide dismutase (SOD) and the quantitative
      change of MDA were measured by biochemical method; changes of free radical were
      determined by 2, 7-dichlorofluorescin diacetate (DCFH-DA) probe with confocal
      microscopy. The results showed that of MTT assay and TUNEL indicated that IAA/HRP
      could significantly inhibit cell proliferation (P < 0.05) and induce apoptosis of
      K562 cell (P < 0.01), at the same time a positive correlation was found between
      apoptosis rate and IAA concentration (r = 0.971, P < 0.01). The activity of SOD
      and the quantitative of MDA increased, accompanied with a rise in IAA
      concentration. Results detected by DCFH-DA probe indicated that the fluorescence
      intensity of intracellular free radical increased, as compared with control, and
      a positive correlation was found. It is concluded that IAA/HRP can inhibit
      proliferation of K562 cells and induce K562 cell apoptosis, its mechanism may be
      related with the increase of intracellular free radical due to the effects of
      IAA/HRP.

PMID- 16277840
TI  - [Mechanism of differentiation and apoptosis in leukemia cells induced by
      tributyrin].
AB  - To elucidate the possible mechanism of differentiation and/or apoptosis in NB4,
      K562 cells induced by tributyrin (TB), a histone deacetylase inhibitor (HDACi),
      the level of acetylated histone H3 was detected by Western blot, p21(WAF1)
      expression was detected by semi-quantitative RT-PCR. The results showed that
      histone H3 hyperacetylation was detected in NB4 (or K562) cells after treatment
      with TB 0.1 mmol/L (or TB 0.5 mmol/L) for 16 hours in a dose-dependent manner.
      p21(WAF1) dose-dependently increased at RNA level in these two cell lines treated
      by TB 0.1 mmol/L. The level of p21(WAF1) mRNA increased at 2 hours after TB
      treatment, reaching peak at 16 hours, and maintaining for 48 hours. In
      conclusion, the mechanism of differentiation and apoptosis in NB4, K562 cells
      induced by tributyrin may associate with its up-regulation of acetylated histone
      and p21(WAF1) mRNA level.

PMID- 16277841
TI  - [Anti-apoptosis effect of VEGF on the human chronic myelocytic leukemia cell line
      K562].
AB  - To explore the effects of vascular endothelial growth factor (VEGF) on the
      mechanisms of CML pathogenesis, the effect of VEGF on K562 cell apoptosis induced
      by As(2)O(3) was analyzed through morphologic observation, DNA fragmentation
      agarose gel electrophoresis and DNA ploidy flow cytometry analysis, and the
      effect of VEGF on the expression of bcl-X(L), Bax and caspase-3 in K562 cells was
      determined by Western blot, meanwhile the expression difference between bcl-X(L)
      and Bax mRNA in above conditions was detected by RT-PCR. The results showed that
      after VEGF added, the apoptosis of K562 cells reduced, however, there was no
      significant changes in cell cycle distribution (P > 0.05). At the same time,
      following the increasing of the concentration of VEGF, expression of mRNA and
      protein of bcl-X(L) was up-regulated and the expression of Bax protein was down
      regulated in K562 cells, and the activation of pro-caspase-3 into caspase-3 was
      inhibited or reduced. It is concluded that VEGF may suppress the apoptosis of
      K562 cells through its influence on the bcl-X(L)/Bax expression ratio in K562
      cells.

PMID- 16277842
TI  - [ATM expression in K562 and SiHA cell lines in relation to their cell cycle
      restardation after gamma-irradiation].
AB  - Ataxia telangiectasis is caused by the mutation of AT gene (ATM) and it is
      characterized by hypersensitivity to the radiation. In order to investigate the
      relationship between ATM mRNA expression of K562 and SiHA two kinds of tumor cell
      lines and their cell cycle restardation after gamma-irradiation, their ATM mRNA
      expressions were measured by semi-quantitive RT-PCR and the cells were irradiated
      at the dose of 6, 10 and 15 Gy of (60)Co gamma ray and the change of the
      apoptosis and cell cycle arrest phenomenon were observed at the time of 6, 12,
      24, 48 and 60 hours after irradiation. The results showed that the ATM mRNA
      relative expression level of K562 cell line was 0.04, that of SiHA cell line was
      0.80, the ATM transcript levels in SiHA cells were 20 times as much as that in
      K562. In conclusion, the G(2)/M phase restardation after irradiation was observed
      in both cell lines, whereas SiHA exhibited a much stronger cell cycle
      restardation, a self-protection function, than that of K562.

PMID- 16277843
TI  - HLA-DRB1 allele polymorphosm associated with susceptibility to leukemia in Han
      nationality of Gansu.
AB  - The study was aimed to explore the possible association between HLA-DRB1 allele
      polymorphism and the susceptibility to leukemia in Gansu Chinese Han nationality
      and to find the genes susceptible to leukemia. HLA-DRB1 genes in 74 patients with
      leukemia from northwestern China and 82 healthy Chinese controls were determined
      by polymerase chain reaction and sequence-specific oligonucleotide probe
      hybridizations (PCR/SSO) DNA analysis. The results showed that as compared with
      control, the allele frequencies of HLA-DRB1*03 (chi(2) = 8.125, P = 0.004), HLA
      DRB1*07 (chi(2) = 13.526, P = 0.000), HLA-DRB1*08 (chi(2) = 18.855, P = 0.000),
      HLA-DRB1*13 (chi(2) = 7.039, P = 0.008) significantly increased in AML group. The
      allele frequencies of HLA-DRB1*07 (chi(2) = 5.689, P = 0.017), HLA-DRB1*11
      (chi(2) = 7.73, P = 0.005), HLA-DRB1*12 (chi(2) = 4.234, P = 0.040), HLA-DRB1*13
      (chi(2) = 38.333, P = 0.000) significantly increased in CML group. The allele
      frequency of HLA-DRB1*01 (chi(2) = 5.294, P = 0.021) significantly increased in
      ALL group. It is concluded that the susceptibility to AML in Gansu Han
      nationality is positively related to HLA-DRB1*03. 1*07.1*08.1*13. CML positively
      correlates with HLA-DRB1*07. 1*11.1*12.1*13, and ALL may be positively in
      relation with HLA-DRB1*01. Allele polymorphism is associated with the leukemia
      occurrence.

PMID- 16277844
TI  - [Tryptase relation to VEGF in acute leukemia].
AB  - In order to investigate the role of tryptase in angiogenesis of acute leukemia
      (AL), the expressions of tryptase and vascular endothelial growth factor (VEGF)
      in leukemic cells from 61 patients with AL were examined by using
      immunocytochemical method, and the correlation between tryptase and VEGF was
      analyzed. The results showed that tryptase positive expression was found in 15
      out of 51 patients with acute myeloid leukemia (AML) (M(1) 1/3, M(2) 7/15, M(3)
      5/20, M(5) 2/8). Tryptase positive expression was 29.4% in AML. However, none of
      10 patients with acute lymphocytic leukemia (ALL) showed tryptase expression.
      There were no correlations between the amounts of cells with tryptase expression
      and patient age, WBC count, numbers of blood or marrow myeloblasts and neutrophil
      POX. VEGF expression was revealed in 41 patients with AML (80.4%) and only 3 with
      ALL (30%). Significant correlation has been found between the expression of
      tryptase and that of VEGF in AML-M(2) (r = 0.65, P < 0.05). It is concluded that
      tryptase appears to be a myeloid-specific marker in AML and may be involved in
      the angiogenesis of AML-M(2).

PMID- 16277845
TI  - [Conventional cytogenetics and fluorescence in situ hybridization as methods for
      detecting MLL gene rearrangements in leukemia].
AB  - This study was aimed to compare the values of conventional cytogenetics (CC),
      interphase FISH and sequential R-banding and FISH analysis as methods for
      detecting MLL gene rearrangements. 37 acute leukemia patients were studied by CC
      and interphase FISH. The results showed that among them, 10 cases were
      11q23(+)/MLL(+), 2 cases were 11q23(-)/MLL(+) (5.4%), 3 cases were 111q23(+)/MLL(
      ) (8.1%) and 22 cases were 11q23(-)/MLL(-). For some patients, different results
      were obtained by using CC and interphase FISH for detecting 11q23/MLL gene
      rearrangements. After sequential R-banding and FISH analysis for 6 patients, the
      chromosome related to MLL gene translocation was seen clearly in karyotypes and
      FISH image. It is concluded that for accurate diagnosis both CC and FISH are
      needed for detecting 11q23/MLL gene rearrangements, and evaluation is needed in
      combination of these two results. When necessary, it needs to do sequential R
      banding and FISH or molecular analysis.

PMID- 16277846
TI  - [JWA gene in regulating committed differentiation of HL-60 cells induced by ATRA,
      Ara-C and TPA].
AB  - The study was aimed to explore the role of gene JWA, a novel retinoic acid
      responsible and cytoskeleton associate gene, in regulating committed
      differentiation of HL-60 cell and the molecular mechanism in the course of
      differentiation and apoptosis of leukemic cells. By using FCM, the changes of
      CD13, CD14, CD15, CD11b and cell cycles were detected in HL-60 cells treated with
      ATRA (10(-6) mol/L), Ara-C (10 ng/ml) and TPA (10(-8) mol/L) respectively. The
      samples were determined by semi-quantitative reverse transcript-polymerase chain
      reaction (RT-PCR) and Western blot for the expression of JWA, Bcl-2, HSP27 and
      HSP70 at day 0, 2, 4, 6, 8. The results showed that HL-60 cells committedly
      differentiated into granulocyte-, monocyte-, macrophage-like cells. As a result,
      JWA was up-regulated in a time-dependent manner, while Bcl-2 was down- regulated
      at the same time. In ATRA and TPA group, the change of HSP70 had positive
      correlation with JWA, and negative correlation with Bcl-2. The expression of
      HSP27 was not detected. Contrast to the cells from APL patient, the expression of
      JWA need not be activated by ATRA in advance. In this study, we also exposed HL
      60 cells in higher dose of Ara-C (20 ng/ml), and JWA expression underwent
      opposite trend comparing with in lower dose of Ara-C (10 ng/ml). It is concluded
      that JWA may play double important roles in regulating ATRA and TPA-induced
      differentiation and apoptosis in leukemic cells. The JWA expression had a
      negative correlation between induction and cytotoxic response. The difference of
      JWA expressions between HL-60 cell and ANLL patient cells would be involved in
      different leukemia pathogenesis.

PMID- 16277847
TI  - [Influence of Qingdai compound on expression of bcr/abl and JWA in K562 cells].
AB  - To study the effects of Qingdai compound on proliferation and apoptosis of K562
      cells, as well as the expression of bcr/abl and JWA mRNA, K562 cells were treated
      in culture with different concentrations of Qingdai compound (2.5, 5, 7.5, 10 and
      20 mg/ml) and harvested at 24 hours. Then morphological changes were observed by
      light microscopy (LM); expressions of bcr/abl and JWA were detected with semi
      quantitative RT-PCR. The results showed that morphological changes were observed
      as the increment of the Qingdai compound concentration. Inhibition effects on
      proliferation and apoptosis in K562 cells were seen. A concentration-dependent
      decreases were found in bcr-abl and JWA mRNA expression of K562 cells. Qingdai
      compound partially inhibited proliferation and induced apoptosis of K562 cells.
      Expressions of both bcr/abl and JWA, which took part in cell proliferation and
      apoptosis, were down-regulated in a dose dependent manner. In conclusion, Qingdai
      compound can partially inhibit the expressions of bcr/abl and JWA genes in K562
      cells, and the clinical effect of Qingdai compound on CML may be associated with
      apoptosis of leukemic cells.

PMID- 16277848
TI  - [CD34+ antigen expression relating to prognosis in acute myeloid leukemia].
AB  - To explore CD34(+) antigen expression in new diagnosed acute myeloid leukemia
      (AML) and analyze the prognosis for CD34(+) AML patients, the expression of
      antigen CD34 in 238 AML patients was detected by indirect immunofluorescence
      assay. The results showed that CD34 in 92 out of the 238 patients (38.7%) were
      positive, there was relationship between the CD34(+) expression and FAB subtypes
      (M(0), M(1)), and no CD34(+) expression was observed in M(3) subtypes. The
      complete remission rate of CD34(+) AML patients was 32%, which was lower than
      that of CD34(-) AML (61%). The lymphoid-associated antigen (CD7) was
      significantly increased in CD34(+) AML patients, compared with CD34(-) patients
      (P < 0.05). It is concluded that CD34(+) AML patients show poor prognosis and
      lower CR rate. The detection of CD34 expression is of some value in predicting
      prognosis in AML.

PMID- 16277849
TI  - [Survivin expression in midline T-cell lymphoma in relation to Epstin-Barr virus
      infection].
AB  - To investigate the expression of survivin gene and its relationship with Epstin
      Barr virus (EBV) infection in midline T-cell lymphoma (MTL), immunohistochemistry
      staining method was used to examine the expression of survivin and EBV-latent
      membrane protein (LMP-1) in the 41 cases. In situ hybridization (ISH) was used to
      detect EBV-encoded RNA (EBER1/2). The results showed that the expression of
      survivin was positive in 26 cases of midline T-cell lymphoma, but no positive was
      detected in 10 cases of reactive lymphoid tissues. The positive expression ratio
      of survivin was 12.5% in cases of MTL with low grade of malignancy, and was
      75.76% in cases of MTL with middle and high grades of malignancy, the significant
      difference was found between these two groups (chi(2) = 8.55, P < 0.01). Positive
      expression ratios of EBER1/2 and LMP-1 were 70.73% and 41.46% respectively.
      Survivin expression was not significantly different between EBER1/2 positive and
      negative cases (P > 0.05). It is concluded that survivin expression is up
      regulated in MTL, and survivin positive expression rate is associated with the
      degree of malignancy. Survivin may play a role in the pathogenesis of the MTL by
      influencing cell apoptosis. EBV infection is not significantly associated with
      survivin expression in the MTL.

PMID- 16277850
TI  - [Expression of human ERMAP gene in different cell lines].
AB  - To investigate the pattern of human ERMAP gene expression in different cell
      lines, 15 cell lines derived from hematopoietic tumor, somatic tumor and normal
      tissue were chosen and were cultured; cells were harvested after culture for 12,
      24, 36, 48, 60 and 72 hours; the expression of the human ERMAP was detected by
      using fluorescent quantitative PCR. The results showed that human ERMAP gene
      expression was positive in K562 cell line at interval of 12 and 24 hours, and the
      expression levels were (5.092 +/- 2.331) x 10(6) cps/microl RNA, (5.328 +/-
      3.916) x 10(6) cps/microl RNA, respectively; ERMAP gene expression was also
      positive in ECV304 cell line at interval of 24 hours, and the expression level
      was (0.84 +/- 0.12) x 10(6) cps/microl RNA; and its expression was negative in
      other 13 cell lines. It is concluded that human ERMAP gene expression in ECV304
      cell line was found first, and its expression in K562 cell line was further
      confirmed.

PMID- 16277851
TI  - [Expression of BLM mRNA in six tumor cell strains].
AB  - The mutations of BLM gene may result in Bloom's syndrome which includes
      immunodeficiency, predisposition to malignant tumors and so on, and enhances
      sister chromati exchange (SCE), DNA replication failure, genome instability, and
      increases cancer susceptibility. This study was aimed to investigate the
      variability of mRNA expression level and cDNA structure of BLM gene in tumor cell
      strains so as to look for a new cancerogenic mechanism and to find a new
      therapeutic target. The expression level of mRNA and the structure of cDNA of BLM
      gene in six tumor cell strains and the normal human bone marrow mononuclear cells
      were detected with RT-PCR and DNA sequencing was performed. The results indicated
      that these tumors cells expressed BLM mRNA higher than the normal human bone
      marrow mononuclear cells (P < 0.01), but no cDNA sequence abnormality of BLM gene
      in these tumors cells was observed. It is concluded that the increase of
      expressing level of BLM mRNA may play an important role in the development of
      these tumors.

PMID- 16277852
TI  - [Construction of FAS-targeted RNAi-retroviral vector and its identification for
      biological activity].
AB  - This study was aimed to construct mouse Fas-targeting si RNA-expressing
      recombinant retroviral vector in order to explore the therapeutic potential of
      Fas inhibition by siRNA in the treatment of aplastic anemia and to provide a
      basia for extensive development of RNA interference techninque. The U6(+) 27
      promoter cassette and siFas sequence were obtained by PCR method. The U6-siFas
      fragment was cloned into the multiple restriction site of pLXSN-EGFP and directly
      downstream of EGFP gene. The resultant retroviral vector pLXSN/EGFP-siFas was
      packaged using PA317 cell line and tittered using NIH3T3 cell line. P815 cells
      were infected by the retroviral vector. EGFP expression in P815 was observed
      under fluorescent microscope and Fas inhibition effect was detected by
      immunohistochemistry. The results indicated that successfully constructed
      retrovirus vector pLXSN/EGFP-siFas was could not only deliver siRNA into
      mammalian cells efficiently and inhibit Fas expression in P815 cells, but also
      could express EGFP as marker and neomycine resistance gene to allow antibiotic
      selection. It is concluded that the successful construction of this retroviral
      vector would greatly facilitate the application of RNA interference and lay the
      foundation for therapeutic study of Fas inhibition in the treatment of aplastic
      anemia.

PMID- 16277853
TI  - [Biological characteristics of mesenchymal stem cells from bone marrow of
      patients with aplastic anemia].
AB  - To investigate the differences of proliferation capacity and phenotype properties
      of mesenchymal stem cells (MSCs) derived from bone marrow (BM) of aplastic anemia
      patients, fetuses and children, MSCs were isolated from BM of patients with
      aplastic anemia and expanded in vitro; MSCs derived from BM of fetuses and
      children were used as normal control groups, three sources of MSCs were compared
      by morphology, in vitro proliferation capacity, phenotype and
      immunocytochemistry. The results showed that MSCs could be isolated and expanded
      from aplastic anemia patient BM. MSCs derived from BM of aplastic anemia patients
      shared a similar morphology and phenotype with derived MSCs from BM of fetuses
      and children. However, in vitro proliferation capacity of MSCs derived from BM of
      aplastic anemia patients after 20 population doublings (PD) was significantly
      lower, compared with MSCs from BM of fetuses and children. BM MSCs derived from
      children and fetuses proliferated for more than 30 PD. It is concluded that BM
      MSCs from aplastic anemia patients appears to be normal in phenotype but their
      proliferation capacity is lower in comparison with control groups.

PMID- 16277854
TI  - [In vitro biological characteristics of mesenchymal stem cells from patients with
      myelodysplastic syndrome and their support to hematopoiesis].
AB  - To study the biological characteristics of mesenchymal stem cells (MSC) from
      patients with myelodysplastic syndrome (MDS) and their supportive capacity for
      hematopoiesis in vitro, MSCs from bone marrow samples of MDS patients were
      isolated, cultured and expanded. Morphology, immunophenotype, osteoblasts
      differentiative and proliferative property of MSC and colony forming unit
      fibroblast (CFU-F) were measured and analyzed. Mononuclear cells (MNC) of cord
      blood were plated onto a feeder layer formed by MSC of MDS patient, cells count
      and CFU-GM production were observed. The results showed that the culture-expanded
      cells from MDS patients presented a typical fibroblast-like morphology. Cells
      were positive for SH2 (CD105), SH3 (CD73), Thy-1 (CD90), but negative for CD34
      and CD45. After induction, these cells could differentiate into osteoblasts.
      Their proliferative capacity and CFU-F number were similar to those of MSC from
      healthy donors. The total cell count and CFU-GM yield in supernatants after
      culture for 2 weeks were significantly lower than those of control in
      hematopoiesis supportive experiments in vitro (P < 0.05). It is concluded that
      the biological characteristics of MSC from bone marrow of MDS patients are not
      different from those of MSC isolated from bone marrow of normal donors, however,
      their capacity of hematopoiesis support in vitro are significantly weaker.

PMID- 16277855
TI  - [Monitoring CML28 mRNA levels in patients before and after HSCT by real-time
      quantitative RT-PCR].
AB  - The purpose of this study was to establish a SYBR Green I real-time quantitative
      RT-PCR method for investigating the correlation between CML28 mRNA expression
      levels and relapse of leukemia after allo-hematopoietic stem cell transplantation
      (HSCT). pcDNA3.1HisA-CML28 plasmid had been constructed as the standard template.
      Serial monitoring of CML28 mRNA levels by SYBR Green I real-time quantitative RT
      PCR technique was performed in 14 patients, including 10 patients with CML and 3
      patients with AML, 1 patient with Ph(+) ALL. The results showed that the
      sensitivity of the established method was at 10(-4) (0.05 ng) level, with
      interassay variation and intraassay variation of standard samples both below 10%.
      The CML28 was highly expressed in AML and CML-BP or AP. CML28 level in newly
      diagnosed group was (6.58 +/- 2.34) x 10(-2), in pre-conditioning regimen group
      was (2.19 +/- 0.32) x 10(-2), in group that 1 month after HSCT was (1.35 +/-
      1.28) x 10(-2), in group that 3 months after HSCT was (4.57 +/- 6.39) x 10(-3).
      CML28 can be detected 3 months after HSCT in 1 patient with CML-CP and 3 patients
      with CML-AP or BC. 2 of them with low level (<2 x 10(-2)) survived without
      relapse, the other 2 case with high level (>2 x 10(-2)) relapsed within one year,
      1 case died and 1 case received the second time HSCT, CML28 level decreased
      rapidly after HSCT, but still higher than 2 x 10(-2) and relapse has taken place.
      The conclusions was made that CML28 mRNA level is obviously correlated with the
      development of leukemia. Serial quantification of CML28 mRNA levels are necessary
      for HSCT recipients, and more informative than a single detection. Using of this
      assay to evaluate MRD in the patients received HSCT is helpful for prediction of
      relapse.

PMID- 16277856
TI  - [Biological activity of C II TA anti-sense RNA--a novel approach to inhibition of
      rejection in transplantation].
AB  - Allo-cell transplant rejection is associated with class II major
      histocompatibility complex (MHC II), while its transactivator (namely C II TA)
      regulates MHC II molecules expression strictly and exclusively. The aim of this
      study was to investigate the inhibiting effect of C II TA anti-sense RNA on MHC
      II expression. The cDNA for anti-sense RNA recognizing the 114-523 sequence of C
      II TA (arC II TA) was obtained from Raji cell by RT-PCR, and then inserted into
      the pcDNA3.1B plasmid (pcDNA3.1B-arC II TA, pD-arC II TA). Raji cells were
      transfected stably with pD-arC II TA, classic MHC II antigen (HLA-DR, -DP, -DQ)
      expression was assayed by flow cytometry (FCM). mRNA abundance of C II TA,
      invariant chain and classic MHC II were detected by RT-PCR. The results showed
      that compared with control (sense C II TA), the expression inhibition of HLA-DR, 
      DP, -DQ on pD-arC II TA positive Raji cell was 65.93%, 54.14%, 68.32%
      respectively. The mRNA contents of C II TA, invariant chain and classic MHC II
      also decreased. In conclusion, arC II TA inhibited C II TA and thus the family of
      MHC II molecules were regulated by it, therefore these results provide a novel
      approach for the control of graft versus host diseases.

PMID- 16277857
TI  - [Effects of mobilization with medium dose of rhG-CSF on the immunocyte component
      of peripheral blood in donors].
AB  - To investigate the changes of donor's peripheral blood immunocytes after
      mobilization with medium-dose recombinant human granulocyte-colony stimulating
      factor (rhG-CSF), the amounts of immunocytes in peripheral blood cells and the
      immunocyte components of donor peripheral blood mononuclear cells (PBMNC) in 12
      healthy donors were detected by flow cytometry before and after mobilization with
      rhG-CSF 10 microg/(kg.day). The results showed that the median amounts of
      peripheral blood leukocytes before mobilization was 6.25 (4.7-7.8) x 10(9)/L, for
      lymphocytes it was 2.07 (1.63-3.10) x 10(9)/L, and for monocytes it was 0.163
      (0.078-0.414) x 10(9)/L. In the fifth day after mobilization, the median amounts
      of peripheral blood leukocytes was 37.47 (24-72.57) x 10(9)/L, and for
      lymphocytes it was 3.22 (1.46-5.31) x 10(9)/L, and for monocytes, it was 1.2
      (0.706-3.627) x 10(9)/L. The average amount of leukocytes after mobilization was
      6.26 +/- 2.14 multiple of that before mobilization (P < 0.01), and the median
      amounts of lymphocytes after mobilization was 1.45 +/- 0.76 multiple of that
      before mobilization (P < 0.05), and the amount of monocytes after mobilization
      was 7.48 +/- 4.41 multiple of that before mobilization (P < 0.01). The median
      percentage of CD3(+) T lymphocytes before mobilization was 46.96% [(32.36
      57.45)%], but 40.94% [(25.31-48.9)%] after mobilization. The ratio of
      CD4(+)/CD8(+) before mobilization was 1.27 +/- 0.46, while 1.36 +/- 0.51 after
      mobilization. The median percentage of CD4(+)CD8(+) T lymphocytes was 0.41%
      [(0.16-1.51)%], and 0.49% [(0.09-2.0)%] after mobilization. The median percentage
      of CD16(+)CD56(+) NK cells was 13.98% [(4.08-25.08)%] versus 16.65% [(12.06
      33.05)%] after mobilization. The median percentage of CD3(+)CD16(+)CD56(+) NK-T
      cells was 2.75% [(0.37-6.38)%], but 3.13% [(0.46-5.95)%] after mobilization. The
      median percentage of CD20(+) B cells was 9.28% [(5.97-16.33)%], while 9.94%
      [(7.36-20.41)%] after mobilization. The median percentage of CD14(+) monocytes
      was 12.48% [(3.54-19.35)%] versus 29.52% [(16.51-36.76)%] after mobilization. The
      percentage of CD3(+) T lymphocytes, CD4(+)CD8(+) T lymphocytes, NK cells, NK-T
      cells and B lymphocytes in PBMNC did not change markedly before and after
      mobilization with middle-dose rhG-CSF. The ratio of CD4(+)/CD8(+) did not change
      significantly (P > 0.10). The percentages of CD14(+) monocytes in PBMNC after
      mobilization increased up to 2.87 +/- 1.51 higher than that before mobilization
      (P < 0.05). It is concluded that the changes of the CD14(+) monocytes after
      mobilization with rhG-CSF may be involved in graft rejection and graft versus
      host disease after allo-PBSCT.

PMID- 16277858
TI  - [In vivo effect of rhG-CSF on the CXCR-4 expression of hematopoietic progenitor
      or stem cells in bone marrow and peripheral blood].
AB  - To investigate the effect of in vivo rhG-CSF on the CXCR-4 expression of
      hematopoietic progenitor or stem cells in bone marrow and peripheral blood, the
      expressions of CXCR-4 on CD34(+) cells and mononuclear cells of bone marrow and
      peripheral blood from healthy donor before and after mobilization were detected
      by three-color fluorescence analysis. The results showed that a significantly
      higher expression of CXCR4 on CD34(+) cells of bone marrow and mononuclear cells
      of peripheral blood, as compared to those before mobilization. There were no
      significant differences of CXCR-4 expression of CD34(+) cells in peripheral blood
      after mobilization, as compared with steady state bone marrow, and no dynamic
      change of mononuclear cells expressing CXCR-4 in bone marrow before and after
      mobilization. Significant positive correlation were found between the percentage
      of CD34(+) cells in bone marrow before mobilization and that in bone marrow and
      peripheral blood after mobilization; furthermore, the percentage of CD34(+) cells
      of bone marrow before mobilization had a positive correlation with both the count
      of CD34(+) cells per kilogram on the day of collection in bone marrow and
      peripheral blood after mobilization. It is concluded that the mobilization of
      hematopoietic cells may be involved in the signaling of SDF-1/CXCR-4 according to
      the increase of the surface expression of CXCR-4 on CD34(+) cells in bone marrow
      and on the MNC in peripheral blood after mobilization; meanwhile, the high
      surface expression of CXCR-4 may contribute to the MNC engraftment, monitoring
      the percentage of CD34(+) cells in bone marrow before mobilization can be
      regarded as a predictive factor for mobilization outcome.

PMID- 16277859
TI  - [Retrospective observation of curative effects on MDS refractory anemia with
      combination of all-trans retinoic acid, 1, 25-dihydroxyvitamin D3 and androgen].
AB  - This study was aimed to examine whether a combination of all-trans retinoic acid
      (ATRA), 1, 25-dihydroxyvitamin D(3) and androgen possesses the therapeutic value
      for the MDS-refractory anemia (MDS-RA), and to analyze the mechanisms in detail.
      62 cases receiving a scheme of combination of ATRA, 1, 25-dihydroxyvitamin D(3)
      and androgen (group A) were monitored. The remaining 33 cases (group B) were
      provided with vitamin supplementation, chalybeate drugs, and one or two of the
      combination. Bone marrow aspiration and biopsy were performed for collecting the
      specimens at the baseline and afterwards. The conditions of the patients were
      monitored by means of weekly complete blood counts and the monthly examination,
      including toxicity test, physical examination, electrocardiography, and
      biochemistry panel. The results showed that after treating for 8 weeks in group
      A, 4 out of 62 patients showed complete remission and 12 patients showed partial
      remission according to the defined response criteria, and 43 patients (69.35%)
      showed hematological improvement (HI). The further treatment for 16 out of 62
      patients (25.81%), 13 failures (10 deaths, 2 RAEB and 1 RAEB-T) and 3
      transformations (M(2), M(3), M(5)) with a median survival interval of 26.25
      months, were observed and interrupted for some reasons. However, partial
      remission was observed only in 3 patients in group B, and HI amounted to 51.51%.
      Furthermore, the disease progression was observed in 12 out of 33 patients
      (36.36%) with a median survival interval of 16 months, 9 failures (including 6
      deaths, 2 RAEB and 1 RAEB-T) and 3 transformations (M(2), M(3), M(4)). The
      overall ratios of survival for 3 and 5 years in group A, which received the
      combination, reached to 69.24% and 53.72% respectively, in comparison with 52.23%
      and 31.34% in the patients of group B (log-rank, P = 0.016). The following
      requirements, if were met, would be significant for prognosis: the combination
      regiment, no transformation, children, no complication, female, 90-120 g/L of
      hemoglobin concentration, normal cellular bone marrow and uni-cytopenias (P <
      0.05). Moreover, Cox regression showed that therapy, transformation and age are
      all the independent factors (P < 0.05). It is concluded that the combination of
      above mentioned 3 drugs may be effective and safe treatment for the patients with
      MDS-RA. Its relevant mechanisms can be involved in the combination, that elicits
      a wide range of pharmacological effects, such as differentiation, anti-tumor
      promotion, anti-apoptosis, anti-angiogenesis, anti-cachexia and immunoregulation.

PMID- 16277860
TI  - [Cyclosporine A based therapy for myelodysplastic syndrome].
AB  - To determine the efficacy and tolerance to cyclosporine A (CsA) based therapy in
      patients with myelodysplastic syndrome (MDS), 16 patients with MDS consisting of
      10 refractory anemia (RA) and 6 refractory anemia with accessory blasts less than
      10% (RAEB-1) were analyzed. Five patients had hypocellular bone marrows and 11
      patients had normocellular or hypercellular marrows. The dose of CsA was 2.5-5.5
      mg/(kg.d) for 2 weeks to 2 years (mean 8 months). Two out of 16 patients were
      treated with CsA alone, 14 patients were treated with CsA, recombinant human
      erythropoietin, androgens, 1, 25 dihydroxy vitamin D(3) or two or three of them
      combination with CsA. Treatment responses were classified according to the
      International Working Group (IWG) criteria as complete remission (CR), partial
      remission (PR), hematological improvement (HI) and no response (NR). Patients who
      obtained CR, PR or HI were defined as responders. The results showed that HI was
      observed in 12 patients, PR in 2 patients and NR in 2 patients. Total response
      rate was 87.5%. Response rates shown in neutrophil lineage, platelet and
      erythroid lineage were 83.3%, 66.7% and 60%, respectively; their shortest time
      required to obtain some hematologic improvement after initiation of CsA therapy
      was 2 weeks, 1 month and 1 month, respectively. Of 13 patients being transfusion
      dependent before treatment, 3 patients did not need transfusion any more and 5
      showed the reduced transfusion requirements after CsA therapy. In 10 patients
      with RA, 9 responded to CsA. Of 6 patients with RAEB, 1 patient had no response
      and died of RAEB-t and 5 patients had transient responses. One of the latter
      transformed to CMML and two relapsed. The total response rate decreased to 50% in
      the patients with CsA therapy lasting more than 3 months at the end of following
      up. The adverse effects included hirsutism, hyperplastic gingiva, reversible
      hepatic and renal dysfunction. In conclusion, the usefulness of CsA based therapy
      for MDS-RA and RAEB-1 with any marrow cellularity is useful, the CsA dose of 3-5
      mg/(kg.d) is safe and efficacious.

PMID- 16277861
TI  - [Expression of apoptosis-related proteins in bone marrow neutrophils of patients
      with paroxysmal nocturnal hemoglobinuria].
AB  - This study was aimed to evaluate expression levels of CD166, Fas and apoptosis
      related proteins in bone marrow neutrophils of PNH patients and normal controls,
      and to analyze their correlation in order to explore whether exist apoptosis
      abnormality in BM neutrophils of PNH patients. The expression levels of CD16b,
      Fas and Bax, Bcl-2 in BM neutrophils of PNH patients and normal controls were
      assayed by flow cytometry; the difference of expression levels between patients
      and controls, and expression correlation between CD16b and apoptosis-related
      proteins were compared. The results showed that (1) the expression levels of
      CD16b on BM neutrophils of patients and controls were (20.36 +/- 9.05)% and
      (71.34 +/- 26.8)% respectively (P = 0.01); (2) the expression levels of CD95 on
      BM neutrophils of patients and controls were (62.83 +/- 32.11)% and (48.00 +/-
      38.52)% respectively, there were no significant difference between CD95
      expressions in BM neutrophils of PNH patients and controls and no significant
      correlation between expression of CD95 and CD16b on BM neutrophils of PNH
      patients (P > 0.05); (3) the expression levels of Bcl-2 in BM neutrophil
      cytoplasma of patients and controls were (8.64 +/- 5.40)% and (16.82 +/- 15.39)%
      respectively, there were no significant difference between Bcl-2 expression of
      patients and controls, and no significant correlation between the expression of
      Bcl-2 and CD16b in BM neutrophil cytoplasma of PNH patients (P > 0.05); (4) the
      expression levels of Bax in BM neutrophil cytoplasma of patients and control were
      (30.47 +/- 22.15)% and (48.47 +/- 15.99)% respectively, there were no significant
      difference between the Bax expressions of patients and controls, and no
      significant correlation between the Bax and CD16b expressions in BM neutrophil
      cytoplasma of PNH patients. In conclusion, BM neutrophils of PNH patients
      expressed apoptosis-related CD95, Bcl-2 and Bax without significant difference
      from the normal controls, and without significant correlation with the CD16b
      expression. It is suggested that the cell growth and decrease of PNH patients
      possibly are independent of abnormal apoptosis.

PMID- 16277862
TI  - [Correlation of newborn hemolytic disease with ABO antibodies in sera of pregnant
      women].
AB  - To investigate the relations between morbidity of hemolytic diseases of newborn
      and ABO antibodies (HDN) in sera of Han and Yao nationality, pregnant women were
      examined before and after delivery. Antibodies screen, direct antiglobulin test,
      free antibodies and elution test were all performed. The results indicated that
      immunologic ABO antibodies of Han people were found in 673 cases out of 1,471 Han
      pregnant women, and was also found in 28 cases out of 65 Yao pregnant women, and
      there was no significant difference of incidences between Han and Yao
      nationality. 31 cases of HDN were found out of 288 newborn in Han and 3 cases of
      HDN were found out of 25 newborn in Yao, and there was no significant difference
      between Han and Yao nationalities. The characteristics of HDN in Han nationality
      were as same as in Yao nationality. In conclusion, the morbidity of HDN in Han
      and Yao nationalities of Shaoguan area did not showed essential difference, the
      immunologic ABO antibodies and its titration test, especially, elution test are
      important for prognosis of HDN.

PMID- 16277863
TI  - [Comparison of modification of surface xenoantigens on bovine and porcine
      erythrocytes].
AB  - This study was aimed to explore impact of removal of cell membrane G alalpha1
      3Gal beta1-4Glc NAc epitopes (called alpha-Gal) and chemical modification of
      other xenoantigen on bovine red blood cell (bRBC) and porcine red blood cell
      (pRBC) antigenicity and to compare their modified erythrocytes, in order to
      provide basis for development of human blood substitute with rich source, high
      safety and efficacy. bRBC and pRBC were subjected to both enzymatic removal of
      membrane alpha-Gal with recombinant coffee bean alpha-galactosidase (rC alpha
      GalE) and covalent attachment of benzotriazole carbonate-linked
      methoxypolyethylene glycol (mPEG-BTC, MW = 20 kD). The effects of treatment were
      measured by hemagglutination, flow cytometric assay of IgG binding and clinical
      cross-match testing to human sera. The results showed that although alpha
      galactosidase treatment reduced hemagglutination titers to levels similar to
      negative control, the combination of the treatments was most effective.
      Clinically used cross-match tests between bRBC, pRBC and human sera demonstrated
      increased compatibility. Bovine RBC were more robust than pRBC, and had less
      xenoantigens, and had longer half life than pRBC in vivo. These characteristics
      suggested that bRBCs were more suitable to investigation as an alternatives to
      hRBC in clinical transfusion than pRBC. These data suggested that strategies to
      remove or mask xenoantigens on bRBC reduce antigenicity sufficiently to allow in
      vitro cross-match compatibility to human sera, and therefore bRBC following
      modification may be considered as human blood substitute.

PMID- 16277864
TI  - [Lyophilization for platelet preservation].
AB  - To explore a new lyophilized preservation methods for human platelets, platelets
      were pre-treated with aldehyde, human albumin or trehalose was added to the
      system of condensed cooling as protectant to stabilize the structure of
      platelets. The optimal resuspending buffer was also selected in the study. The
      morphological changes of platelets were observed by using electron microscopy
      after lyophilization, and the expression of membrane proteins on platelets was
      detected also after lyophilization. The results indicated that the recovery rate
      of platelets treated with aldehyde was generally more than 60%. Aggregative
      ability was reduced a little than the platelet untreated. 5% of human albumin had
      an advantage over 40 mmol/L of trehalose in respect of the preservation effect.
      In the way of keeping aggregative ability, PPP was obviously better than PBS. The
      results of electron microscopy displayed that organelles including mitochondria
      and excreted granules could be observed distinctly. Whereas, expression of
      membrane proteins of platelet treated with aldehyde was evidently dropped as
      compared with those of the fresh platelet. In conclusion, aldehyde as a novel
      protective agent, has excellent effects on lyophilization of platelets and is
      worthy to be further studied.

PMID- 16277865
TI  - [Analysis of genetic polymorphism in randomized donor's HPA 1-16 antigens and
      establishment of typed platelet donor data bank].
AB  - To study the genetic polymorphism of HPA 1-16 platelet antigen alleles among
      unrelated volunteer donors and establish a typed platelet donor panel in Handan,
      typing was perfomed by polymerase chain reaction using sequence-specific primers
      (SSP-PCR); 148 random unrelated blood donors in Handan were genotyped for each of
      the HPA 1-16 antigen. The gene frequencies were analyzed and the genetype
      frequencies were determined by direct counting, and these data were compared with
      HPA distribution among various population by the chi-square test. The results
      indicated that HPA-1a, 2a, 4a-14a, 16a genes were found among the 16 HPAs in
      every sample tested. Monomorphic HPA-4a, 7a-14a, 16a were found in the samples.
      For HPA-1, 2, 5 and 6, a/a homozygosity was predominant with frequencies of
      0.9595, 0.8108, 0.9865, 0.9797, respectively, and none of HPA b/b was found in
      the samples. HPA-1b, 2b, 5b, 6b were rarely found among subjects. HPA-15 had the
      greatest heterozygosity with a gene frequency of 0.2230, 0.5270, 0.2500 for
      HPA15a/15a, HPA15a/15b, HPA15b/15b, respectively. HPA-3 showed the second
      greatest heterozygosity with a gene frequency of 0.3851, 0.5135, 0.1014 for
      HPA3a/3a, HPA3a/3b, HPA3b/3b, respectively. HPA genotype frequencies showed a
      good fit to Hardy-Weinberg equilibrium. HPA1-5 gene frequencies for Chinese
      people in Handan were consistent with those of Chinese people in Shijiazhuang (P
      > 0.05). Among the HPA1-13, -15, the frequencies of HPA-1, -2, -6 for Chinese
      people in Handan differed appreciably from those for Chinese people in Taiwan (P
      < 0.05), others were similar to those of Chinese people in Taiwan. Among the HPA
      1 - 8, a similarity was noted between Chinese people in Handan and Koreans (P >
      0.05), except for HPA-3. Frequencies of HPA-1, -2, -5 significantly were differed
      from those in African Americans, as compared with HPA 1-5 (P < 0.05). Comparison
      of gene frequencies from HPA-1 and -5 showed significant differences between
      Chinese people in Handan and people in UK (P < 0.05). It is concluded that HPA-2,
      -3, -5, -15 of people in Western region of China have polymorphism, incompatible
      frequency of HPA antigen distribution is higher, which inevitably results in the
      increase of immunologic exposure, therefore attention must be paid to the
      importance of HPA-2, -3, -5, -15 in clinical disorders. This study for the first
      time completely analyses HPA1-16 gene frequencies in China, and provides data for
      establishing a typed platelet donor panel in Handan, China.

PMID- 16277866
TI  - [Tendency and mathematical model of relationship of blood ATP content with
      temperature and time of preservation].
AB  - To investigate the relationship of blood ATP content with temperature and time of
      preservation and to establish its mathematical model, adenosine triphosphate
      (ATP) concentration was applied as the index of the quality of erythrocytes;
      systematical study on variation of blood preserved in a series of different
      temperatures from 4 degrees C to 32 degrees C was performed, and a series of
      experimental data were obtained. The results showed that when the ATP
      concentration y = f (d, t, s) in preserved blood was given as the continuous
      function of the time (d), the temperature (t) and the initiate ATP concentration
      (s), the model was fitted with the theory of linearity regression in symbolic
      statistics, and the general mathematical physical equation of the variation of
      preserved blood quality was deduced. According to the equation, the whole blood
      in CPDA-1 solution could be efficiently stored for 35, 35, 29, 22, 18, 18, 13, 8,
      7, 6, 6, 5, 4, 4 and 3 days in 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28,
      30 and 32 degrees C, respectively. In conclusion, the general tendency of the
      variation of preserved blood quality according to the temperature and the time
      was systematically disclosed for the first time, which would be propitious to
      estimate the blood quality in various temperatures and to instruct clinical blood
      transfusion.

PMID- 16277867
TI  - [Establishment of beta block matching technique].
AB  - The purpose of this study was to establish beta block matching technique. DNA was
      extracted from whole blood by salting-out method, beta block matching was
      performed by PCR and GeneScan technique. The results showed that the length of
      fragments amplificated in 100 samples was different and the range of them was 91
      197 bp. Amplification fragments could be divided into four regions: 91-93, 105
      113, 125-139 and 177-197 bp respectively. 91 bp DNA fragments could be found in
      all of samples. The numbers of DNA fragments with different length have been
      shown high polymorphism and they focused on the range of seven to twenty four. In
      conclusion, the beta block matching technique is reliable and applicable to the
      selection of hematopoietic stem cell transplantation donors.

PMID- 16277868
TI  - [Cold storage of platelet suspension by adding trehalose].
AB  - The study was aimed to explore the trehalose method for storing platelets in
      cold. (51)Cr-labeling platelet was used to detect the platelet survival. The
      platelet function in vitro was performed by platelet aggregate analyzer. After
      treatment with 50 mg/ml trehalose at 37 degrees C for 4 hours, the rabbit
      platelet concentrates (PC, 2.0 x 10(9)/ml) were stored in 4-8 degrees C
      refrigeration, the platelet function in vitro and survival of chilled platelets
      transfused into self-rabbits were observed. The results showed that trehalose
      could protect the chilled rabbit platelets. After PC stored at 20-24 degrees C
      and 4-8 degrees C for up to 24 hours, the platelet aggregate in vitro in response
      to 11.2 micromol/L ADP were (75.3 +/- 9.8)% and (80.5 +/- 12.5)%, the survival of
      PC stored at 20-24 degrees C and 4-8 degrees C for 24, 48, 72 hours after
      transfused into self-rabbits were (78.1 +/- 7.9)%, (65.4 +/- 6.7)%, (57.5 +/-
      7.2)% and (5.1 +/- 2.5)%, (2.8 +/- 2.0)%, (0.9 +/- 0.8)%, respectively. The PC
      treated with 50 mg/ml trehalose were remained stable for up to 12 days of
      refrigerated storage in autologous plasma. The platelet aggregate in vitro in
      response to 11.2 micromol/L ADP at 12 days after stored in refrigeration was
      (77.8 +/- 9.5)%, the survival on 24, 48, 72 hours of platelet transfused into
      self-rabbits were (75.7 +/- 11.0)%, (67.0 +/- 8.5)%, (56.8 +/- 8.0)%,
      respectively. Compared with control group of storing at 20-24 degrees C for 24 h,
      P > 0.05. In conclusion, trehalose can protect the chilled blood platelets,
      prolong the circulation of refrigerated rabbit platelets, and not impair chilled
      rabbit platelet function.

PMID- 16277869
TI  - [Immunomodulation of bone marrow mesenchymal stem cells in hematopoietic stem
      cell transplantation--review].
AB  - Bone marrow mesenchymal stem cells (BM-MSC) have the characteristics of self
      renewal and multipotency. They secrete a variety of cytokines and provided and
      ideal microenvironment for the division, proliferation and differentiation of
      hematopoietic stem cells (HSC) through the interaction with other stromal cells.
      Previous studies indicated that MSC could enhance engrafment and alleviate GVHD
      in allo-HSC and MSC co-transplantation. This effect on transplantation immunity
      may associate with escaping MHC compatible HSC from antigen recognition and
      suppressing activation and proliferation of nonspecific lymphocytes. In this
      paper, the characteristics of BM-MSC influencing transplantation immunity and its
      mechanism were reviewed.

PMID- 16277870
TI  - [Folate receptor and its application in the selective receptor-mediated targeting
      therapy of tumor cells--review].
AB  - A series of receptors expressed in the surface of tumor cells, which are able to
      mediate internalizing effect by specially connecting with corresponding ligands.
      These receptors are potential targets for drugs combined with conjugates. So the
      drug-conjugate compounds can be targeted delivery to tumor cells. The folate
      receptor is a promising target because of its marrow tissue specificity, its
      overexpression in malignant tissues, especially in myeloid leukemic cells, and
      its ability to bind and internalize folic acid conjugates. It is a promising
      potential method to apply folate receptor in the receptor-mediated targeting
      therapy of leukemic cells. In this review, the biological features of folate
      receptor, its chromosome location and its interaction with ligands, the
      distribution characteristics of folate receptor in normal and tumor tissues,
      especially in myeloid leukemic cells, and progress of research on folate receptor
      mediated targeting tumor cells, especially leukemic cells were summarized.

PMID- 16277871
TI  - [Advances in the studies of humanized anti-platelet antibody--review].
AB  - Platelet plays an important role in bleeding and thrombotic diseases. Humanized
      anti-platelet antibodies have great clinical effects in treatment of ITP and
      preventing thrombosis. The important role of platelet in bleeding and thrombotic
      diseases, the present status of development on study of humanized anti-platelet
      antibody and its application in treatment of bleeding and thrombotic diseases
      were summarized in this review.

PMID- 16277872
TI  - [Vascular endothelial progenitor cells and cytokines related to hematopoietic
      regulation--review].
AB  - Endothelial progenitor cell (EPC) is a subtype of progenitor cells that can
      circulate, proliferate and have the ability to differentiate into mature
      endothelial cells. Exploration of EPC have significance to understand the
      vascular forming process of adults physiologically and pathologically. Cytokines,
      especially haematopoiesis-related cytokines, cellular stimulating factors in the
      body also influence EPC. In this review, the advances of research on the
      relationship between EPC and some cytokines related with haematopoiesis (G-CSF,
      EPO, HAPO and IL-18) and the potential signal transduction pathway were
      summarised.

PMID- 16277873
TI  - Hemodynamics under Hippocampal Functional Hyperemia in Anesthetized Rat: A
      Greater Contribution of Red Blood Cell Velocity Compared to Its Concentration.
AB  - It remains controversial which of the two regulators, red blood cell velocity
      (RBC-V) or concentration (RBC-C), is a main contributor to increasing flow (RBC
      F) during functional hyperemia in the rat hippocampus induced by N-methyl-D
      aspartate (NMDA). To address this, we monitored these parameters simultaneously
      under NMDA-infusion via microdialysis in the hippocampus of urethane-anesthetized
      rats and found a greater elevation in RBC-V than in RBC-C. This suggests that an
      RBC-V-dependent increase in RBC-F occurs under NMDA-induced functional hyperemia
      in the hippocampus as well as in the cortex.

PMID- 16277874
TI  - Cardiac developmental biology: from flies to humans.
AB  - The heart is the first organ to form during embryogenesis, and heart formation is
      essential for subsequent embryonic development. Since the identification of a
      cardiac-restricted transcription factor Csx/Nkx-2.5 in the early 1990s, extensive
      studies on cardiac development have been done in various species ranging from
      flies to humans. Molecular dissection of regulatory pathways that control
      multiple steps of cardiogenesis will not only advance our understanding of
      cardiac development and congenital heart diseases, but will also provide an
      important clue to novel therapeutic strategies for heart diseases.

PMID- 16277875
TI  - Transforming technologies and breast cancer.

PMID- 16277879
TI  - Defining the roles of aromatase inhibitors in the adjuvant treatment of early
      stage breast cancer.
AB  - The widespread use of tamoxifen has led to significant improvements in survival
      for postmenopausal women with early-stage hormone receptor-positive breast
      cancer; however, approximately 30% of patients die despite receiving tamoxifen as
      adjuvant treatment. In addition, concerns exist regarding tamoxifen-associated
      side effects, including endometrial cancer and thromboembolic disease. The
      development of the third-generation aromatase inhibitors (AIs; anastrozole,
      exemestane, and letrozole) therefore represented a welcome potential alternative
      to tamoxifen. Several clinical trials have demonstrated the superiority of AIs
      over tamoxifen in the adjuvant treatment of postmenopausal women with hormone
      sensitive breast cancer, but these trials differ in their design and in the
      characteristics of their patient populations. This review discusses the different
      designs of the primary adjuvant, switching, extended adjuvant, and sequencing
      trials that are investigating the use of AIs in the adjuvant treatment of breast
      cancer and provides direction regarding how the data from these trials could be
      used to guide treatment choice. This review also demonstrates why one should not
      extrapolate results from clinical trials to clinical situations that differ from
      the clinical trial or from clinical trials investigating a particular AI to
      clinical situations involving another AI.

PMID- 16277880
TI  - Ductal carcinoma in situ of the breast in men: a review.
AB  - Breast carcinoma in men is rare and comprises approximately 1% of all breast
      cancer cases. In contrast to the increase in the detection rate of ductal
      carcinoma in situ (DCIS) in women resulting from the wide use of screening
      mammography programs, the rate of male DCIS is still small and represents
      approximately 5% of all male breast cancers. Considerable debate exists
      concerning the nature of this entity, including the clinical course, pathologic
      findings, treatment, and prognosis. In this review, the relevant literature
      dealing with male DCIS is summarized in an attempt to more precisely define the
      features of this disease.

PMID- 16277881
TI  - Predictive value of biologic parameters for primary chemotherapy in operable
      breast cancer.
AB  - Primary chemotherapy represents an ideal model to evaluate the relationships
      between treatments and the prognostic and predictive parameters provided by the
      new technologies. First- and second-generation trials have shown that primary
      chemotherapy significantly improves the rate of breast conservation without
      increasing the risk of ipsilateral recurrence and while assuring survival rates
      comparable with those achieved with postoperative chemotherapy. Moreover,
      patients who exhibited a pathologic complete response (pCR) showed better
      progression-free survival and overall survival. The third-generation trials were
      aimed at improving the percentage of pCR, identifying and validating gene and
      protein biomarkers of chemotherapy sensitivity, and better defining the
      individual risk of relapse. Several parameters, such as index of proliferation
      and apoptosis, expression of proteins (eg, p53 and Bcl-2), and hormone receptor
      and epidermal growth factor family receptors, have been related to response to
      primary chemotherapy. Negative hormone receptors and greater proliferative
      activity seem to be the only parameters more consistently associated with greater
      chemotherapy sensitivity. However, the strength of this association is not
      sufficient to differentiate patients at different degrees of risk and does not
      allow for an individualized therapeutic choice. Newer technologies offer the
      possibility of evaluating thousands of genes and identifying clusters of gene
      expression associated with significantly different risks of relapse and patterns
      of sensitivity/resistance to specific drugs. The primary chemotherapy model is
      the ideal clinical setting in which to validate the relationship between tumor
      molecular profiling and treatment outcomes and to design tailored therapies based
      on observed effects on individual tumors.

PMID- 16277882
TI  - Trastuzumab associated with successive cytotoxic therapies beyond disease
      progression in metastatic breast cancer.
AB  - PURPOSE: To determine the activity of successive trastuzumab-containing regimens
      in HER2-overexpressing metastatic breast cancer (MBC) as well as the response
      rate (RR), time to progression (TTP), and predictive factors for response.
      PATIENTS AND METHODS: We performed a descriptive retrospective study of
      trastuzumab activity in patients with HER2-overexpressing MBC treated at our
      hospital from October 1999 to October 2003. RESULTS: Fifty-eight patients were
      evaluated, in whom an overall RR (complete response plus partial response) of
      39.7% was obtained for first-time administration of trastuzumab; stable disease
      (SD) was seen in 29.3%, and the clinical benefit rate was 69%. Median TTP was 6
      months (range, 1 months to > 39 months). A total of 31 patients (53.4%) received
      a second trastuzumab-containing regimen, with an RR of 25.8%; SD was seen in
      12.9%, and the clinical benefit rate was 38.7%. Median TTP was 3 months (range, 1
      months to > 22 months). A total of 8 patients (14.3%) received a third
      trastuzumab-containing regimen. The RR for the third trastuzumab regimen was
      12.5%; SD was seen in 12.5%, and the clinical benefit rate was 25%. Median TTP
      was 2 months (range, 1 months to > 12 months). A total of 4 patients (7.1%)
      received a fourth trastuzumab-containing regimen, with an RR of zero and SD in
      25%. Predictive factors for response were disease in soft tissue or bone (P =
      0.03; odds ratio [OR], 3.25; 95% confidence interval [CI], 1.08-9.8) and
      metastases at < 2 sites (P = 0.03; OR, 6.2; 95% CI, 1.25-30.9). We observed a
      better RR in the second trastuzumab-containing regimen when the patient responded
      to the first regimen (P = 0.03; OR, 13.2; 95% CI, 1.36-126). CONCLUSION:
      Trastuzumab-containing regimens beyond disease progression in MBC show activity
      even in heavily pretreated patients. The activity noted does not allow us to
      ascertain the independent contribution of trastuzumab in this setting. There were
      more responses in patients with few metastases in the soft tissues or bone.
      Patients who have shown a previous response to trastuzumab can show a response to
      a second trastuzumab-containing regimen.

PMID- 16277883
TI  - Importance of physical examination in the absence of a mammographic abnormality
      for the detection of early-stage breast cancer.
AB  - PURPOSE: A recent trial called into question the efficacy of breast self
      examination. We studied the characteristics and outcome of women in whom physical
      examination (PE) was their sole method of breast cancer detection. PATIENTS AND
      METHODS: From 1970 to 1998, 1752 women with stage I/II breast cancer underwent
      breast-conserving surgery and radiation. Two hundred sixty patients (15%) had
      abnormal PE finding as their sole method of cancer detection at the time of
      diagnosis, 723 (41%) had only mammographic findings, and 762 (43%) had both.
      RESULTS: Detection by PE was associated with younger age, larger tumor size,
      positive axillary nodes, and use of chemotherapy. For women < 40 years of age, PE
      was the sole method of detection in 40% of cases. The patients for whom PE was
      the sole method of detection had equivalent 10-year locoregional control and
      overall survival (OS) compared with patients whose cancer was detected by
      mammography. Detection by PE was not an independent predictor for outcome on
      multivariate analysis. The use of tamoxifen (P = 0.0089) was the sole predictor
      for improved locoregional control. Tumor stage (P = 0.0001), nodal status (P =
      0.039), age (P = 0.0112) and lymphovascular invasion (P = 0.0399) were negative
      predictors of OS. CONCLUSION: Although associated with younger age, larger
      tumors, and more frequent node positivity, in this study detection by PE did not
      confer worse outcome. This may be because of the increased use of chemotherapy in
      these patients. Physical examination remains an important method of detection of
      breast cancer, particularly for younger women for whom mammography is less
      sensitive and not performed as frequently.

PMID- 16277884
TI  - Single-agent topotecan as first-line chemotherapy in women with metastatic breast
      cancer: final results of eastern cooperative oncology group trial E8193.
AB  - PURPOSE: The purpose of this multicenter phase II trial was to evaluate the
      clinical activity of topotecan as first-line chemotherapy in patients with
      metastatic breast cancer and previous exposure to adjuvant doxorubicin. PATIENTS
      AND METHODS: Patients with measurable disease received a 72-hour continuous
      intravenous infusion of topotecan 1.3 mg/m(2) per day repeated every 21 days. The
      primary objective was to determine whether > or = 4 responses were observed among
      30 evaluable patients after 3 cycles of therapy using a 2-stage design (> or = 2
      responses required in the first 20 evaluable patients). Duration of response,
      time to tumor progression, overall survival, and toxicity were also examined.
      Thirty-five patients altogether received 78 cycles of therapy (median, 3 cycles;
      range, 1-8 cycles). RESULTS: Two partial responses (6%; 95% confidence interval,
      0.7%-19%) were observed among 30 evaluable patients (median age, 55 years; range,
      34-76 years; median Eastern Cooperative Oncology Group performance status, 0;
      range, 0-2). Median time to progression and overall survival were 2.3 months and
      18.7 months, respectively. Myelosuppression was the most common toxicity among 34
      evaluable patients (grade 3/4 neutropenia and thrombocytopenia in 62% and 53%,
      respectively) with only 1 life-threatening event. CONCLUSION: Although tolerable,
      this dose and schedule of topotecan has limited activity in unselected patients
      with breast cancer even as first-line therapy. Identification of potential
      predictive markers of response and toxicity is encouraged before considering
      further studies of topotecan and camptothecin analogues in breast cancer.

PMID- 16277885
TI  - Tissue-type plasminogen activator is upregulated in metastatic breast cancer
      cells exposed to insulin-like growth factor-I.
AB  - The insulin-like growth factor (IGF) system plays an important role in breast
      tumorigenesis. Breast cancer cells express the type I IGF receptor (IGF-IR) and
      respond to IGFs in the environment. Tissue-type plasminogen activator (tPA) has
      been shown to be associated with neoplastic transformation and the invasive
      phenotype for highly aggressive tumors; however, its role in breast cancer
      remains unclear. We asked whether there is a relationship between the IGF system
      and tPA in estrogen receptor-negative breast cancer cells that could contribute
      to invasion. When MDA-MB-435s breast cancer cells were exposed to IGF-I, tPA
      messenger RNA (mRNA) was upregulated in a time-dependent fashion. Tissue-type
      plasminogen activator protein accumulation was also increased in a similar
      manner. The invasiveness of MDA-MB-435s cells was enhanced in the presence of IGF
      I. When the MDA-MB-435s cells were stably transfected with an antisense IGF-IR
      expression construct, the transfectants expressed high levels of IGF-IR
      antisense, dramatically reduced levels of endogenous IGF-IR, and a decrease in
      relative staining intensity for IGF-IR protein. A marked suppression in tPA mRNA
      expression occurred in MDA-MB-435s cells accompanying inhibition of IGF-IR. When
      cells carrying the antisense IGF-IR expression construct were exposed to IGF-I,
      tPA protein accumulation was significantly lower than that of control transfected
      cells. To our knowledge, this study is the first to show a relationship between
      the IGF system and tPA. Strategies that target the IGF/tPA pathway could provide
      alternative treatments for patients with certain types of metastatic breast
      cancer.

PMID- 16277886
TI  - Paget's disease of the nipple as local recurrence after breast-conservation
      treatment for early-stage breast cancer.
AB  - Breast conservation treatment (BCT) for early-stage breast cancer is associated
      with survival rates comparable with mastectomy but has the risk of ipsilateral
      breast tumor recurrence, including Paget's disease of the nipple. A small number
      of cases of Paget's disease presenting as local recurrence following BCT for
      breast cancer have been previously reported. Between 1977 and 2002, 2181 women
      with early-stage breast cancer were treated with BCT at the Hospital of the
      University of Pennsylvania. In this cohort, there were 183 local treatment
      failures, 4 of which were cases of Paget's disease (2.2%), which are reported
      herein. These local recurrences developed 1.8, 3.8, 7.3, and 9.7 years after
      diagnosis of the patients' primary tumors. Three of the 4 primary cancers were
      invasive ductal carcinomas, with an associated intraductal component, and 1 was
      ductal carcinoma in situ. All 4 patients were successfully given salvage therapy
      consisting of mastectomy with or without tamoxifen, with follow-up times of 20.9,
      10.6, 3.1, and 3.8 years. Paget's disease as local recurrence after BCT is
      uncommon and can be treated with salvage therapy if detected early.

PMID- 16277887
TI  - Treatment of metastatic breast cancer with trastuzumab and vinorelbine during
      pregnancy.
AB  - The management of breast cancer during pregnancy is a crucial clinical issue. It
      is important to evaluate the impact of chemotherapy on a woman and her fetus.
      Studies from our institution have demonstrated the safety and efficacy of
      treating women with adjuvant 5-fluorouracil/doxorubicin/cyclophosphamide during
      the second or third trimester of pregnancy. However, the literature regarding the
      treatment of metastatic breast cancer in a pregnant patient is scarce. In this
      article, we describe the successful treatment of a woman at 27 weeks of pregnancy
      with recurrent HER2/neu-overexpressing breast cancer who was symptomatic from
      multiple liver metastases. Per our review of the literature and to our knowledge,
      she is the first patient to be treated with weekly vinorelbine plus trastuzumab.
      Our patient had near complete resolution of her disease and delivered a healthy
      male infant at 34 weeks of gestation.

PMID- 16277888
TI  - Potential role of mammalian target of rapamycin inhibitors in breast cancer
      therapy.

PMID- 16277889
TI  - North Central Cancer Treatment Group N0531: Phase II Trial of weekly albumin
      bound paclitaxel (ABI-007; Abraxane) in combination with gemcitabine in patients
      with metastatic breast cancer.

PMID- 16277890
TI  - [Study on different hysterectomy].

PMID- 16277891
TI  - [Clinical study on different operation procedure for hysterectomy].
AB  - OBJECTIVE: To investigate the effects and outcomes of four procedures for
      hysterectomy. METHOD: Retrospectively, we analyzed the clinical characteristics
      of 756 cases who respectively received hysterectomy by total abdominohysterectomy
      (TAH, 260 cases), modified abdominohysterectomy (MAH, 180 cases), transvaginal
      hysterectomy (TVH, 106 cases), or laparoscopic assisted vaginal hysterectomy
      (LAVH) (210 cases) and compared their effects and outcomes. RESULTS: The average
      operation time of TAH (98 +/- 23) minutes, MAH (67 +/- 18) minutes, TVH (63 +/-
      19) minutes and LAVH (99 +/- 35) minutes. The average operation time of LAVH and
      TAH groups was significantly longer than that of TVH and MAH groups (P < 0.05).
      The volume of hemorrhage during operation in TAH group (180 +/- 49) ml was much
      more than that of other three groups significantly [MAH (102 +/- 43) ml, TVH (93
      +/- 31) ml, LAVH (111 +/- 39) ml]. The average time of antibiotic administration
      and bowel function recovery in TAH group [(5.2 +/- 2.6) days, (36 +/- 9) hours]
      was significantly longer than that of TVH [(3.2 +/- 1.6) days, (21 +/- 4) hours],
      LAVH [(3.5 +/- 1.9) days, (23 +/- 6) hours] and MAH [(3.3 +/- 1.7) days, (23 +/-
      7) hours] (P < 0.05). The incidence of fever in TAH group was significantly
      higher than that of other three groups also. The average hospital stay after
      operation in TVH [(3.3 +/- 1.2) days] and LAVH [(3.6 +/- 1.1) days] groups was
      significantly shorter than that of MAH [(5.6 +/- 1.9) days] or TAH [(5.4 +/- 2.3)
      days] groups (P < 0.05). CONCLUSIONS: Different procedures for total hysterectomy
      have their own advantages and disadvantages. Microinvasive surgery by laparoscopy
      for hysterectomy will be mainstream in the future.

PMID- 16277892
TI  - [Clinical comparison of transvaginal hysterectomy and laparoscopic hysterectomy].
AB  - OBJECTIVE: To compare the clinical characteristics of transvaginal hysterectomy
      (TVH) and total laparoscopic hysterectomy (TLH). METHOD: Clinical data about 301
      cases who received TVH and TLH were collected and the hospital stay days, medical
      expenses, diagnoses, operation and recovery status were compared between TVH and
      TLH groups. RESULTS: The ratio of cervical atypical hyperplasia (9.64%),
      multipara (96.45%) in TVH was higher than that in TLH (2.88%, 89.42%). The ratio
      of adenoma (29.44%), adnexal disease (4.55%), pelvic endometriosis (4.06%),
      history of cesarean section (7.11%) in TVH were lower than that in TLH (43.27%,
      31.73%, 12.50%, 24.04%). The operation time (76 +/- 28) minutes, bleeding during
      operation (170 +/- 125) ml, additional operations (5.08%), pelvic adhesion
      (4.57%), loosening of pelvic adhesion (0.51%), the diameter of the largest myoma
      or adenoma (49 +/- 17) mm, expenses for operation and hospitalization (1073 +/-
      203) yuan in TVH were lower than those in TLH, which were (139 +/- 52) minutes,
      (206 +/- 153) ml, 36.54%, 41.35%, 17.31%, (57 +/- 22) mm, (1526 +/- 676) yuan
      respectively. The differences were significant (all P < 0.05). There was no
      difference of the uterine weight, complication and length of hospitalization
      duration between the two kinds of operation. CONCLUSIONS: TVH is recommended in
      cases of few pelvic adhesion, or adnexal disease, cervical disease and of
      multipara. The uterine weight is not a decisive factor.

PMID- 16277893
TI  - [Clinical analysis of 45 cases of vaginal myomectomy].
AB  - OBJECTIVE: To evaluate the feasibility, clinical effect and safety of vaginal
      myomectomy. METHOD: From January 2002 to April 2004, 45 cases treated by vaginal
      myomectomy were analyzed as the study group, and 45 cases treated by abdominal
      myomectomy during the same period in our hospital were selected as the control
      group. Effects of operation and recovery of two groups were compared. RESULTS:
      There were no significant differences in the mean operating time, blood loss
      during operation between the study group, (76 +/- 21) minutes, (414 +/- 73) ml
      and the control group, (72 +/- 26) minutes, (404 +/- 68) ml. In the study group,
      the mean recovery time of bowel function (18 +/- 9) hours and average
      postoperative hospital stay (4.8 +/- 0.6) days were shorter than in the control
      group (31 +/- 8) hours, (7.8 +/- 0.4) days. For two groups menorrhagia were
      relieved after 6.8 months' follow-up, patients in the study group recovered more
      rapidly and felt more satisfactory with the effect of operation than patients in
      the control group. CONCLUSION: Vaginal myomectomy can be performed in selected
      patients with minimum operative injury, low complications and good short-time
      effect compared with abdominal myomectomy.

PMID- 16277894
TI  - [Primary study of vasculogenic mimicry induced by hypoxia in epithelial ovarian
      carcinoma].
AB  - OBJECTIVE: To explore possibility of vasculogenic mimicry induced by hypoxia and
      the inhibitive effect by sirolimus in epithelial ovarian carcinoma in vitro.
      METHODS: Based on three-dimensional cell culture system developed by Matrigel,
      ovarian cell lines SKOV3 and ES2 were induced under conditions of hypoxia,
      hypoxia added with sirolimus and no-hypoxia, respectively. Potential formation of
      tumor channels and their characterization of network were observed by light
      microscopy and scanning electronic microscopy. Relative hypoxia-inducible factor
      (HIF) 1alpha mRNA expression was detected by RT-PCR simultaneously. RESULTS: The
      micrograph showed both SKOV3 and ES2 cells appeared expanded and re-shaped, then
      formed blood vessel-like structures such as cavity, channel, branch and network.
      These capabilities of cells were inhibited by sirolimus and no-hypoxia. The
      levels of HIF-1alpha mRNA expression of SKOV3 and ES2 were 0.801 +/- 0.034 and
      0.736 +/- 0.059 under hypoxia, which were significantly higher than under hypoxia
      added with sirolimus (0.025 +/- 0.007, 0.231 +/- 0.035; P < 0.01, P < 0.05), and
      those under no-hypoxia (0.010 +/- 0.004, 0.011 +/- 0.002; both P < 0.01).
      CONCLUSIONS: Hypoxia plays a key role in development of vasculogenic mimicry in
      epithelial ovarian carcinoma. Sirolimus can inhibit vasculogenic mimicry
      effectively by blocking HIF-1alpha at transcription level.

PMID- 16277895
TI  - [Study of the prevention of chemotherapy-induced ovarian damage by gonadotropin
      releasing hormone agonist in rat model].
AB  - OBJECTIVE: To study the effect of gonadotropin-releasing hormone agonist (GnRHa)
      against cyclophosphamide (CTX) induced gonado toxicity in female rats. METHODS:
      Eighty Fischer 344 rats were divided into four groups which received normal
      saline, CTX, GnRHa and CTX + GnRHa respectively. We measured the serum estradiol
      and follicle-stimulating hormone (FSH) concentration monthly, and respectively
      killed half of the rats two months and three months later to compare the weight
      of the ovary, the numbers of the follicle and the mean diameter of the follicles.
      RESULTS: After three months, in the rats in the CTX group, the serum estradiol
      and FSH were (148.3 +/- 16.5) pmol/L and (16.90 +/- 1.90) U/L respectively. They
      were significantly higher than (91.8 +/- 9.9) pmol/L and (7.60 +/- 0.30) U/L in
      the rats in the combination therapy group (P < 0.05). The follicle number of rats
      in the CTX group was 550 +/- 50 and the follicle number in the combination group
      was 1250 +/- 160. There was significant difference between two groups (P < 0.05).
      Between rats in the control and combination therapy groups, there was no obvious
      difference in all the indexes we examined. CONCLUSIONS: Combination of the CTX
      and GnRHa in the rat model could decrease the CTX-induced damage to the ovarian
      function.

PMID- 16277896
TI  - [Study on hepatitis B virus intrauterine infection state and its correlation
      factors].
AB  - OBJECTIVE: To investigate the correlation factors of hepatitis B virus (HBV)
      intrauterine infection and the influence factors of HBV infection in peripheral
      blood mononuclear cells (PBMC) and placentas. METHODS: HBeAg and HBsAg in 151
      pregnant women and their newborns were determined by enzyme linked
      immunoadsorbent assay (ELISA). HBV DNA in serum and PBMC of pregnant women and
      their newborns were determined by polymerase chain reaction. HBsAg in 151
      placentas were detected by immunohistochemistry ABC. The correlation risk factors
      were analyzed by non-condition logistic regression model. RESULTS: HBV DNA
      positive in serum, HBV DNA positive in PBMC of pregnant women and HBsAg positive
      in placentas were the risk factors for HBV intrauterine infection. Their odds
      ratio (OR) and 95% confidence interval were 2.25 (1.08-4.72), 2.69 (1.26-5.73)
      and 4.63 (1.70-12.62), respectively. The influence factors of HBV infection in
      placenta included antepartum injection of hepatitis B immunoglobulin (HBIG) over
      thrice and HBV DNA positive in serum of pregnant women with OR 0.08 (0.01-0.69)
      and 4.24 (1.22-14.69). The risk factor for HBV DNA positive in PBMC of newborns
      was HBV DNA positive in PBMC of their mothers with OR 24.53 (7.92-76.01).
      CONCLUSIONS: HBV infection in placentas, HBV DNA positive in PBMC and serum of
      pregnant women are the risk factors for HBV intrauterine infection. Antepartum
      injection of HBIG over thrice can protect placentas from being infected by HBV to
      some extent. PBMC HBV DNA positive in pregnant women is probably the independent
      risk factor for PBMC HBV intrauterine infection in newborns.

PMID- 16277897
TI  - [Study on correlation between histocompatibility leukocyte antigen class II gene
      and gestational diabetes mellitus].
AB  - OBJECTIVE: To investigate correlation between part of histocompatibility
      leukocyte antigen (HLA) class II gene and gestational diabetes mellitus (GDM).
      METHODS: Part of HLA-II gene was examined by polymerase chain reaction sequence
      specific primer (PCR-SSP). Forty-eight GDM women were served as study group, and
      forty-eight normal pregnant women were selected as control group. RESULTS: The
      frequencies of DRB1*0301, DRB1*1302 and DQA1*0301 of GDM (18.8%, 45.8% and 64.6%)
      in study group were significantly increased compared with control group (4.2%,
      18.8% and 41.7%) (P < 0.05). CONCLUSIONS: The results suggest that there is
      correlation between HLA class II gene and gestational diabetes mellitus.
      DRB1*0301, DRB1*1302 and DQA1*0301 are the susceptible alleles of GDM.

PMID- 16277898
TI  - [Study on the association between gestational diabetes mellitus and tumor
      necrosis factor-alpha gene polymorphism].
AB  - OBJECTIVE: To study allelic frequency of tumor necrosis factor-alpha (TNF-alpha)
      in gestational diabetes mellitus (GDM) of Han ethnicity in north China and to
      determine whether there is a specific allele of TNF-alpha associated with GDM
      susceptibility. METHODS: By using PCR-RFLP, we detected the distribution of TNF
      alpha promoter alleles frequency in GDM women and control normal pregnant women.
      Plasma TNF-alpha levels and insulin levels were measured by radioimmunoassay.
      RESULTS: (1) There was a significant increase of A alleles frequency of TNF-alpha
      promoter -308 gene in GDM women compared with control group (61.4% vs 30.0%, P <
      0.05) and an increase of the AA + GA genotype was observed in GDM group (71.4% vs
      37.1%, P < 0.05). (2) In GDM group, the patients carrying the AA + GA genotype
      had higher plasma TNF-alpha levels (52 +/- 13 vs 14 +/- 4, P < 0.05) and a lower
      insulin sensitivity (13.6 +/- 6.5 vs 1.9 +/- 0.2, P < 0.05) compared with those
      carrying the other genotype (GG). CONCLUSIONS: The 308 G-->A polymorphism of TNF
      alpha promoter gene is involved in the pathophysiology of insulin resistance and
      gestational diabetes mellitus.

PMID- 16277899
TI  - [Usefulness of serum inhibin B measurement for evaluation of ovarian reserve in
      controlled ovarian hyperstimulation].
AB  - OBJECTIVE: To assess usefulness of serum inhibin B (INHB) measurement for
      evaluation of ovarian function. METHODS: Serum INHB level on day 3 of menstrual
      cycle was determined by enzyme labeled immunosorbent assay (ELISA) in 96 cases of
      in vitro fertilization and embryo transfer (IVF-ET). The patients were classified
      into 3 groups including (1) poor response (n = 6), normal response (n = 72), and
      over response (n = 18) according to their response to ovary stimulation. In
      addition, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and
      estradiol (E(2)) levels were also determined by chemiluminescent microparticle
      immunoassay in these patients. Evaluation of the INHB measurement and related
      factors was performed by statistical analysis. RESULTS: Serum INHB levels in
      poor, normal and over-response groups were (28 +/- 20), (85 +/- 42), (92 +/- 34)
      pg/ml; FSH levels were (11.9 +/- 5.3), (7.5 +/- 2.6), (7.2 +/- 1.7) U/L; E(2)
      levels on day 3 of human chorionic gonadotropin (hCG) administration were (2558
      +/- 2108), (9366 +/- 4472), (18 392 +/- 9655) pmol/L; numbers of retrieved
      oocytes per cycle were (0.6 +/- 0.4), (8.7 +/- 3.6), (14.3 +/- 2.9); top grade
      embryos were (0.4 +/- 0.3), (3.8 +/- 1.9), (4.6 +/- 1.7); pregnancy rates were
      16.7%, 36.1%, 61.1%, respectively. INHB level was negatively correlated to FSH (r
      = -0.222, P < 0.05) and FSH/LH (r = -0.371, P < 0.05); while positively
      correlated to E(2) on the day of hCG administration (r = 0.336, P < 0.05), number
      of retrieved oocytes (r = 0.404, P < 0.05), number of quality embryos (r = 0.323,
      P < 0.05) and pregnancy rate (r = 0.246, P < 0.05), respectively. CONCLUSIONS:
      INHB test may reflect the ovarian reserve which is of clinic importance in the
      guidance of controlled ovarian hyperstimulation.

PMID- 16277900
TI  - [Vitrification of human cleaved embryos in vitro fertilization-embryo transfer].
AB  - OBJECTIVE: To assess the outcome of thawing human cleaved embryos from
      cryopreservation by vitrification. METHODS: A total of 957 day 2 or day 3 embryos
      from 219 patients were thawed after vitrification with ethylene glycol 5.5
      solution and 0.25 ml straw between Jan 2003 and Jun 2005, 514 embryos were
      recovered and transferred in 178 patients. RESULTS: The survival rate of thawing
      embryos and the clinical pregnancy rate after transfer was 72.2% and 19.7%
      respectively. Twenty-two healthy babies were born from 16 deliveries, including
      12 girls and 10 boys, 6 pregnancies ended in miscarriage and another 13 are
      ongoing. CONCLUSION: Vitrification method is an alternative for cryopreservation
      of human cleaved embryos because of high effectiveness, convenience and good cost
      efficiency.

PMID- 16277901
TI  - [Effects of selected phages with specific peptide ligands on the biological
      behaviors of ovarian cancer cells].
AB  - OBJECTIVE: To evaluate the effects of the selected phages with the specific
      peptide ligands upon the biological behaviors of the ovarian cancer cells.
      METHODS: Two ovarian cancer cell lines, A2780 and SKOV3, were used in the study.
      They were divided into three groups respectively: study group, blank control
      group and negative control group. The effects of the phages were evaluated by
      trypan blue staining, flow cytometry, colony formation test, methyl thiazolyl
      tetrazolium (MTT) assay and Boyden chamber invasion assay. RESULTS: The average
      viability of ovarian cancer cells of study groups was (72.1 +/- 6.2)%, higher
      than that of negative control group (84.8 +/- 4.6, P < 0.05); the apoptosis ratio
      of the A2780 and SKOV3 cells of study groups increased (20.39% and 43.99% vs 0);
      the average colony formation rate of the ovarian cancer cells was of study groups
      4%, lower than the control group (15%, P < 0.05); the inhibition rates of cell
      proliferation of A2780 and SKOV3 cells of study groups were 11.07% and 9.58%,
      significantly higher than that of their respective negative control (2.05% and
      1.09%); the invasion index of the ovarian cancer cells decreased compared with
      the control. CONCLUSION: The selected phages down-regulate the growth,
      proliferation and invasion ability of the ovarian cancer cells to certain extent,
      the identified peptide ligands may play a role in tumorigenesis and metastatic
      transformation of ovarian cancers.

PMID- 16277902
TI  - [Expression and significance of KiSS-1 and its receptor GPR54 mRNA in epithelial
      ovarian cancer].
AB  - OBJECTIVE: To study the expression and significance of metastasis suppressor gene
      KiSS-1 and its receptor GPR54 in epithelial ovarian cancer. METHOD: The
      expression and their clinical significance of KiSS-1 and GPR54 were evaluated by
      RT-PCR in 37 patients with epithelial ovarian cancer, 15 patients with borderline
      epithelial ovarian tumors, 15 patients with epithelial benign tumors and 11
      patients with normal ovarian tissues. RESULTS: The positivity and relative
      contents of KiSS-1 mRNA in patients with epithelial ovarian cancer (68%, 0.82 +/-
      0.09) and borderline epithelial ovarian tumors (60%, 0.80 +/- 0.10) were all
      higher than in patients with epithelial benign tumor (20%, 0.65 +/- 0.10) and
      normal ovarian tissues (18%, 0.66 +/- 0.06; P < 0.05). The positivity and
      relative contents of KiSS-1 mRNA in patients with epithelial ovarian cancer
      correlated with their clinical stage and lymph node metastasis (P < 0.05). There
      was no difference in the positivity and relative contents of GPR54 mRNA between
      patients with epithelial ovarian cancer (70%, 0.79 +/- 0.07), borderline
      epithelial ovarian tumor (67%, 0.76 +/- 0.10), benign epithelial ovarian tumor
      (60%, 0.73 +/- 0.07) and normal ovarian tissues (45%, 0.78 +/- 0.08),
      respectively (all P > 0.05). The positivity and relative contents of GPR54 mRNA
      in patients with epithelial ovarian cancer did not correlate with their clinical
      stage, histology grade, lymph node metastasis and production of ascites (P >
      0.05). CONCLUSION: KiSS-1 and GPR54 may play an important role in inhibiting the
      invasion and metastasis of early epithelial ovarian cancer.

PMID- 16277921
TI  - [Organization and multidisciplinary treatment of colorectal cancer].

PMID- 16277903
TI  - [Inhibitory effects of human papilloma virus 18 E6 gene in HeLa cell transfected
      with shRNA].
AB  - OBJECTIVE: To investigate the inhibition of HPV18E6 gene in HeLa cell transfected
      with plasmid expressing human papilloma virus 18 E6 (HPV18E6) short hairpin RNA
      (shRNA). METHODS: We synthesized two HPV18E6 shRNA frames and sub-cloned them
      into pSUPER which can express shRNA in mammalian cells to construct pE6-1shRNA
      and pE6-2shRNA which were mutant in E6 shRNA frame. The pE6-1shRNA, pE6-2shRNA
      and pcDNA3.1 were co-transfected into HeLa cells by cationic liposome
      respectively and the positive transfectants were selected by G418. The HPV18E6
      mRNA and protein expression level was detected by semi-quantitative RT-PCR and
      streptavidin-peroxidase conjugated method (SP) to assay the inhibitory effects of
      pE6shRNA. RESULTS: We successfully constructed several new HeLa cell lines
      transfected with pE6-1shRNA and pE6-2shRNA. In the HeLa cells without
      transfection and the HeLa cells transfected with pE6-1shRNA plasmid, the HPV18E6
      mRNA levels were 1.14 +/- 0.45, 0.76 +/- 0.28 respectively, and the difference of
      HPV18E6 mRNA levels was significant (P < 0.05). The inhibition efficiency of
      HPV18E6 gene mRNA was 33.3% and the HPV18E6 protein levels were declined after
      transfection with pE6-1shRNA. In the HeLa cells transfected with pE6-2shRNA and
      pSUPER plasmids, HPV18E6 mRNA and protein expression levels were not different
      from those in wild HeLa cells. CONCLUSIONS: The pE6-1shRNA plasmid can inhibit
      HPV18E6 expression in HeLa cells, which is persistent, specific and heritable.

PMID- 16277922
TI  - [Treatment of rectal cancer].
AB  - Patients with rectal cancer are evaluated with digital examination, endoscopy and
      imaging of the liver and lungs, including biopsies of the primary tumour and
      suspected secondary spread. On the basis of a precise tumour staging by MRI scan
      and/or transrectal ultrasound scan, the combined surgical-oncological treatment
      is discussed at a multidisciplinary treatment conference. Preoperative
      oncological treatment is offered depending on the tumour stage and for selected
      patients may include radiotherapy and chemotherapy. Radiotherapy may be offered
      as a short-term adjuvant treatment or a long-term course with the aim of
      downstaging. The surgical treatment for selected patients includes total
      mesorectal excision or local tumour resection. The prognosis has improved over
      the last decade.

PMID- 16277923
TI  - [Elective treatment of colon cancer: surgical and oncological].
AB  - Around 2,300 new cases of colon cancer are diagnosed in Denmark every year.
      Surgical treatment follows the standard criteria, including removal of as many
      lymph nodes as possible to ensure correct classification of the disease. For
      staging, the sentinel node principal may also be advantageous, but this is not
      yet routine in colon cancer. Patients with Dukes' C disease routinely receive
      adjuvant chemotherapy. For patients with Dukes' B disease, chemotherapy is not
      routine but may be given in selected cases.

PMID- 16277924
TI  - [Drug therapy of patients with metastatic colorectal cancer].
AB  - In less than a decade, metastatic cancer in the colon or rectum has changed from
      being primarily a surgically palliated disease to one in which there have been
      increasing successes with combination chemotherapy and molecular targeted
      therapy. Without treatment, only half of the patients are alive after six months,
      and there are almost no survivors after two years. With modern therapy, about
      half of the patients are now alive after two years and the survival time
      continues to increase. Instead of being a more or less acute life-threatening
      disease, metastatic colorectal cancer may exist as a chronic condition for years.

PMID- 16277925
TI  - [Treatment of local recurrence of rectal cancer].
AB  - The frequency of local recurrence after rectal cancer is expected to decline, as
      surgical techniques and preoperative radiochemotherapy continue to improve. The
      treatment of these difficult cases requires a variety of specialists (in urology,
      reconstructive surgery, radiotherapy and gynaecology). In Denmark the estimated
      number of patients requiring this complex kind of surgery will be 20-30 per year.
      One (maybe two) hospital department will be needed to treat these patients.

PMID- 16277926
TI  - [Treatment of liver and lung metastases from colorectal cancer].
AB  - Metastases from colorectal cancer are most often confined to the liver or lungs,
      in which 20-25% may be resected with curative intent. Without treatment, no
      patients are alive after four years, whereas 30% are alive four years after
      radical resection. Early use of chemotherapy increases survival, and about 20% of
      patients may thus become suited for local therapy. After the primary operation,
      surveillance is recommended, with measurement of carcinoembryonal antigene every
      3-6 months for 3 years, then every 6-12 months from years 3 to 5, plus ultrasound
      or CT scan every 6 months for 3 years, then yearly for up to 5 years.

PMID- 16277927
TI  - [Complications after treatment of colorectal cancer, with special focus on
      stomas, urological conditions and sexual dysfunction].
AB  - In spite of improved surgical principles in colorectal surgery, patients
      undergoing this operation still suffer from long-term postoperative
      complications. Many patients have permanent stomas, and up to 60% have problems
      related to their stomas, the most frequent of these being parastomal hernia. In
      this context, the use of primary prophylaxis with mesh insertion is encouraging.
      Before the introduction of total mesorectal excision (TME), there was a very high
      rate of bladder problems and sexual dysfunction with impotence and retrograde
      ejaculation. The rate has been reduced dramatically since the introduction of
      TME, but up to 5% of patients still suffer from permanent bladder dysfunction and
      complete impotence.

PMID- 16277928
TI  - [Radical surgical resection of leiomyosarcoma of the inferior vena cava with
      intracardial tumour growth].
AB  - Sarcoma of the inferior vena cava (IVC) is a rare clinical entity. Surgical
      treatment of IVC is associated with improved survival. This case report describes
      a 42-year-old woman with biopsy-proven leiomyosarcoma of the inferior vena cava
      with intracardial tumour growth. The primary tumour was only 1 x 1 cm in the wall
      of the vena cava while the intracaval tumour was 12 cm long with a diameter of 5
      cm and 1.5 cm in the right atrium. Using venovenous bypass with circulatory
      support, the tumour was excised in toto and the caval vein closed with a
      pericardial patch. The patient was discharged in good condition after 19 days.

PMID- 16277929
TI  - [Quality monitoring of colon surgeons' volume of operations].
AB  - INTRODUCTION: The number of operations performed by a surgeon is a predictor of
      the outcome of colon/rectum resection. Therefore it is relevant to monitor the
      surgeons' volume of work and the number of patients' complications in order to
      secure both an adequate number and high quality. MATERIALS AND METHODS: Using
      data from the Danish National Patient Registry and Danish Colon Cancer Group's
      database, we located hospital departments that had performed colon/rectum surgery
      in 2003 and asked them whether they monitored surgeons' volume of work and the
      number of patients' complications and whether they considered those data relevant
      to the patients or their GPs. RESULTS: Thirty-nine departments had performed
      colon/rectum resection; 27 of them responded. Eight departments (36%) had defined
      a standard for the number of operations per surgeon, while only four used the
      data to determine the surgeons' volume of work. 68% found data concerning the
      department's volume of operations relevant to both GPs and patients, while 23%
      thought that those data were not relevant to GPs or patients. 64% found the data
      concerning surgeons' volume to be irrelevant to both GPs and patients. None of
      the departments had informed the GPs or the patients about their results.
      DISCUSSION: It is remarkable that very few hospital departments actually collect
      and use data to secure adequate volume and quality. It is necessary to increase
      the focus on surgeons' volume of operations in order to secure high quality.

PMID- 16277931
TI  - [Lumbar puncture].

PMID- 16277930
TI  - [Magnetic resonance colonography: a new diagnostic tool].
AB  - Magnetic resonance colonography (MR colonography) is a three-dimensional imaging
      of the colon. Data postprocessing also allows for virtual colonoscopy, depicting
      the intraluminal morphology. Acquisition and postprocessing of high-resolution
      images require a state-of the-art modern MR scanner and a workstation. Regarding
      patient preparation, a bowel cleansing is necessary. The results of cancer
      screening have shown MR colonography to be superior to the traditional double
      contrast barium enema. In inflammatory bowel disease, MR colonography can be used
      to assess disease activity, including spreading.

PMID- 16277932
TI  - [Emergency medicine in Adelaide].

PMID- 16277937
TI  - [Myopia surgery].

PMID- 16277947
TI  - [C-reactive protein changes with antihypertensive and statin treatment].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the modifications
      of high sensitivity C-reactive protein (CRP) with antihypertensive and statin
      treatment in a hypertensive population with a wide range of coronary risks (CR).
      PATIENTS AND METHOD: Retrospective follow-up study in 665 hypertensive patients:
      556 (52% male) without dyslipidemia and CR (Framingham at 10 years) of 8.3 (7.6)
      as a control group (C) and 109 (61% male) with dyslipidemia and CR of 13.1 (8.8)
      who were treated with statins (T). Statins treatment was established according to
      NCEP-ATP-III. In both groups, the antihypertensive treatment was optimized in
      order to achieve blood pressure (BP) control (< 140/90 mmHg). A lipid profile and
      high sensitivity CRP (analyzed by nephelometry) was performed at the beginning
      and at the end of follow up [14.3 (3.6) months]. RESULTS: CRP levels were reduced
      in the T group -0.17 (0.2) mg/L vs. 0.14 (0.09) mg/L (p = 0.003, Mann-Whitney) in
      C. The lessening of CRP was not related to the reduction of lipids levels: total
      cholesterol (r = 0.06; p = 0.49), LDL-C (r = 0.11; p = 0.24), triglycerides (r = 
      0.02; p = 0.81) (Spearman), or to the reduction of systolic BP (r = -0.07; p =
      0.44) and diastolic BP (r = -0.121; p = 0.21). The T group was treated with more
      antihypertensive drugs than C (2.2 [2.3] vs. 2.5 [1.2]; p = 0.02). Patients
      treated with ECA inhibitors or angiotensin II antagonist showed a tendency to
      decreasing the CRP levels more (p = 0.08). CONCLUSION: In hypertensive
      populations, statins induce a reduction of CRP levels. The reduction is not
      related to the lowering of lipids levels or BP values. The effect of statins on
      the reduction of CRP in hypertensive patients is not related to the lowering of
      lipids or BP.

PMID- 16277948
TI  - [Validation of the Spanish version of the SEAR (Self-Esteem And Relationship
      Questionnaire) for men with erectile dysfunction].
AB  - BACKGROUND AND OBJECTIVE: The aim was to validate the Spanish version of the Self
      Esteem and Relationship Questionnaire (SEAR), specific for patients with erectile
      dysfunction (ED), and based on the concept of self-esteem, for use in research
      and clinical practice in Spain. PATIENTS AND METHOD: Observational, prospective,
      multisite, study comparing patients with ED (IIEF questionnaire score < 26
      points), with a score (3/4) 16 points in the Self-Esteem domain of the SEAR
      questionnaire and undergoing treatment with sildenafil (group A), and healthy
      control subjects without ED. Patients with ED were assessed at baseline and after
      3 months' treatment. RESULTS: Among 586 evaluable subjects (504 patients with ED
      and 82 health subjects) the questionnaire showed: a) adequate feasibility with a
      percentage of patients without response < 5%; b) adequate reliability with
      Cronbach alpha coefficients for the total and all domains (Sexual-Relationship,
      Confidence, Self-Esteem, and Overall-Relationship), of SEAR questionnaire,
      respectively: 0.92, 0.89, 0.84, 0.75, and 0.82 un patients, and 0.86, 0.80, 0.73,
      0.56 and 0.74 un healthy subjects; c) adequate discriminatory validity between
      patients and healthy subjects (Mann-Whitney test, p < 0.0001), and between
      patients with vaying degrees of ED (Kruskall-Wallis test, p < 0.05); d) adequate
      convergent/divergent validity (correlations > 0.5 with the IIEF questionnaire and
      r > 0.3 and < 0.5 with Mental Health domain score of SF-12 questionnaire); e)
      adequate construct validity, obtaining 2 domains: Sexual-Relationship, and
      Confidence, and f) adequate sensitivity to clinical changes (SES: 2.1/SRM:
      1.5/SEM: 4.4/MID: 13.1). Mark scores were estimated. CONCLUSIONS: The Spanish
      version of the SEAR questionnaire showed adequate and similar psychometric
      properties to those shown with the original English version.

PMID- 16277949
TI  - [Myocardial perfusion (SPECT) in patients with non-Q-wave myocardial infarction].
AB  - BACKGROUND AND OBJECTIVE: The denomination non-Q-wave myocardial infarction
      ranges from small infarcts without scintigraphic abnormalities to severe and
      extensive necrosis with scintigraphic criteria of transmurality. The aim of the
      present study was to evaluate the severity and localization of necrosis in
      patients with non-Q-wave myocardial infarct, by myocardial perfusion single
      photon emission computed tomography (SPECT). PATIENTS AND METHOD: We evaluated
      206 patients with non-Q-wave myocardial infarct consecutively studied by
      myocardial perfusion 99mTc-tetrofosmin SPECT. Severity and localization of
      perfusion defects at stress and rest were analyzed. RESULTS: Rest SPECT was
      normal in 53 patients (26%) and in 41 patients (20%) at least one segment with
      scintigraphic criteria of transmurality (uptake absence) was observed. Perfusion
      defects were more frequently localized in inferior and lateral regions. Stress
      rest reversibility in peri-infarct regions was observed in 68.9% of patients, and
      reversibility at a distance was observed in 30% of patients. CONCLUSIONS:
      Myocardial perfusion SPECT is a useful technique for the evaluation of the
      localization, extension and transmurality of non-Q-wave myocardial infarction,
      and the residual peri-infarction ischemia and ischemia at a distance of the
      necrosis.

PMID- 16277950
TI  - [Statins and beneficial effects].

PMID- 16277951
TI  - [Rationale and conceptual design of MASCARA study: a challenge in the evaluation
      of the effectiveness].

PMID- 16277952
TI  - [Treatment of carpal tunnel syndrome].

PMID- 16277953
TI  - [Oral ulcers].
AB  - Ulcers commonly occur in the oral cavity, their main symptom being pain. There
      are different ways to classify oral ulcers. The most widely accepted form divides
      them into acute ulcers--sudden onset and short lasting--and chronic ulcers-
      insidious onset and long lasting. Commonest acute oral ulcers include traumatic
      ulcer, recurrent aphthous stomatitis, viral and bacterial infections and
      necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer,
      benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to
      the group of chronic oral ulcers. It is very important to make a proper
      differential diagnosis in order to establish the appropriate treatment for each
      pathology.

PMID- 16277955
TI  - [Methodologic bias in prevalence studies of smoking habit during pregnancy].

PMID- 16277956
TI  - [Ethics in health decisions].

PMID- 16277957
TI  - [Towards a uniform registry of clinical trials. The role of ethical committees
      and medical journals].

PMID- 16277959
TI  - Chronic administration of propylthiouracil ameliorates hyperdynamic circulation
      in portal hypertensive rats.
AB  - OBJECTIVE: To evaluate the effect of a hypothyroid state, induced by chronic
      propylthiouracil administration, on splanchnic and systemic hemodynamic
      parameters in rats with portal hypertension due to portal vein ligation. METHODS:
      Portal hypertension was induced by surgical stenosis of the portal vein. Cardiac
      index and portal blood flow were measured using radioactive microspheres.
      Measurements were performed after treatment with propylthiouracil (1 mg/ml in
      drinking water) for 5 days. RESULTS: Propylthiouracil-treated portal hypertensive
      rats had a lower portal pressure (12.4 +/- 1.9 versus 16.3 +/- 0.7 mmHg; p <
      0.05) and portal blood flow (11.6 +/- 0.7 versus 13.2 +/- 1.3 ml/min/100 g; p <
      0.05) than non-treated animals. Splanchnic vasoconstriction in treated animals
      was associated with a higher peripheral vascular resistance (2.3 +/- 0.4 versus
      1.8 +/- 0.3 mmHg/ml/min/100 g; p < 0.05) than controls. CONCLUSION: These results
      suggest that portal pressure can be lowered by inducing a hypothyroid state by
      chronic administration of propylthiouracil.

PMID- 16277960
TI  - [Influence of climatic factors on the incidence of upper gastrointestinal
      bleeding].
AB  - OBJECTIVES: Several studies have suggested the existence of seasonal variation in
      the incidence of upper gastrointestinal bleeding (UGB). However, the role of
      climatic factors has not been elucidated. The aim of the present study was to
      investigate the role of these factors in the incidence of UGB secondary to
      esophageal varices (EV), gastric ulcer (GU), and duodenal ulcer (DU). MATERIAL
      AND METHODS: Based on the use of the Minimum Data Set and the International
      Classification of Diseases, cases of endoscopically-confirmed UGB secondary to
      EV, GU and DU were retrospectively included (1998-2001). The incidence of UGB was
      correlated with daily climatic factors (temperature, atmospheric pressure,
      humidity, direction and speed of wind) in Jerez de la Frontera (Spain) during the
      study period. RESULTS: A total of 499 patients were included (GU = 192, DU = 199,
      EV = 108). No significant differences were found in the monthly or seasonal
      incidence of UGB. Episodes of UGB were grouped according to the climatic
      conditions present on the day of admission. No significant relationship was found
      between UGB and any of the daily climatic factors studied. DISCUSSION: The
      results of our study do not support the existence of a seasonal pattern in the
      incidence of UGB secondary to GU, DU or EV and allow us to conclude that, in our
      geographical area, these factors are not involved in episodes of bleeding.

PMID- 16277961
TI  - [Referrals to a gastroenterology outpatient clinic: differences according to
      patients' geographical origin].
AB  - INTRODUCTION: The characteristics of users of the Spanish public health system
      have been evaluated in multiple studies. However, these studies usually refer to
      users of primary care and emergency services and less frequently to users of
      specialized services. Some studies have described differences according to
      patients' geographical origin. OBJECTIVE: To analyze the demographic profile of
      patients attending our gastroenterology outpatient clinic over a prolonged
      period. PATIENTS AND METHOD: The geographical origin, age and sex of all patients
      referred for an initial consultation in the gastroenterology outpatient clinic
      from 2001-2003 were analyzed. RESULTS: Women accounted for 53.7% of all
      appointments but no significant differences in referral rates were observed in
      comparison with men. A total of 65.5% of patients were from urban areas and the
      referral rate was significantly higher in these patients than in those from rural
      areas, although attendance rates were equal between patients from the two types
      of area. Referral rates increased in direct proportion with age; a predominance
      of referrals was observed in women aged < 74 years and in men aged 75 years or
      older. Some discrepancies were found among the distinct years analyzed.
      CONCLUSIONS: In our catchment area, demand is greater in the urban population
      than in the rural population. No overall differences were found in sex but
      significant differences were found in age and length of follow-up.

PMID- 16277962
TI  - [Massive abdominal vein thrombosis with acute liver failure and toxic megacolon
      as onset of ulcerative colitis].
AB  - The prevalence of systemic thromboembolic complications is higher in patients
      with inflammatory bowel disease than in the general population. This
      hypercoagulable state is due to an increased production of procoagulant
      substances proportionally related to the inflammatory activity of the disease,
      although recent reports have focused on the presence of inherited thrombophilic
      disorders in this entity. We present the case of a 32-year-old woman with no
      relevant medical history who presented with massive abdominal vein thrombosis,
      including suprahepatic, portal, splenic and superior mesenteric veins, and
      secondary acute liver failure in her first ulcerative colitis flare and who later
      developed toxic megacolon requiring emergency total colectomy despite steroids
      and cyclosporine. Anticoagulant therapy achieved complete resolution of
      suprahepatic thrombosis and partial resolution in the splenic and superior
      mesenteric veins, with final cavernous transformation of the portal vein.

PMID- 16277963
TI  - [Hepatoportal sclerosis and liver angiosarcoma: an infrequent association with a
      possible common etiology].
AB  - Hepatoportal sclerosis is characterized by fibrosis of the intima of the portal
      vein and its branches leading to the development of presinusoidal portal
      hypertension. We describe the case of a 58-year-old woman with idiopathic
      hepatoportal sclerosis, who was admitted to our service due to impairment of
      liver function, with rapid clinical worsening and finally the development of
      multiorgan failure. Autopsy showed a diffuse liver angiosarcoma with splenic
      metastases. The patient had no history of domestic or occupational exposure to
      substances involved in the development of hepatoportal sclerosis or liver
      angiosarcoma. The development of liver angiosarcoma in a patient with
      hepatoportal sclerosis is exceptional, even though both diseases may have a
      common etiology.

PMID- 16277964
TI  - [General malaise and diarrhea as the main manifestations of Giardia lamblia
      infection].
AB  - Giardia lamblia is a ubiquitous intestinal protozoan. Transmission, which is
      fecal-oral, occurs after cyst ingestion, excystation and enterocyte adhesion.
      Symptoms include diarrhea, abdominal pain and other less frequent manifestations
      such as nausea, anorexia and weight loss. Enzyme immunoassay and direct
      fluorescent-antibody assay for antigen detection in stool samples, and small
      intestine biopsy provide the best diagnostic sensitivity. When an infection is
      suspected, duodenal biopsy should be carried out, even though endoscopic
      appearance may be normal. The most effective drugs in the treatment of this
      infection are metronidazole and tinidazole. We report a case of G. lamblia
      infection. The patient reported a clinical history of 4 months' duration with
      general malaise and diarrhea for the previous month. This form of presentation is
      rarely found in adults with this parasitosis. The diagnosis was based on the
      results of duodenal biopsy. The patient showed satisfactory response to treatment
      with metronidazole.

PMID- 16277965
TI  - [Screening for celiac disease in high risk groups].
AB  - Several epidemiological studies show that celiac disease with extraintestinal
      manifestations is 15 times more frequent than celiac disease with intestinal
      symptoms. Fifteen years ago the iceberg model was proposed to explain the
      epidemiology of this disease. On the one hand, there are a quantifiable number of
      patients who are correctly diagnosed since they have symptoms suggestive of this
      disease and who form the visible part of the iceberg. However, several studies
      using screening serology demonstrate that for each patient diagnosed, there is a
      mean of 5-10 patients without a diagnosis. These patients form the submerged part
      of the iceberg (monosymptomatic or silent celiac disease). The most widely
      accepted strategy to investigate the submerged part of the "celiac iceberg" is
      screening of known risk groups through a systematic search for celiac disease in
      these groups.

PMID- 16277966
TI  - [Prevention of bleeding recurrence in peptic ulcer by Helicobacter pylori
      eradication].

PMID- 16277967
TI  - [Pathogenesis and immunotherapy in inflammatory bowel disease: lessons from
      animal models].

PMID- 16277969
TI  - A combination of walk-back and optimum contribution selection in fish: a
      simulation study.
AB  - The aim of this paper was to study the performance of a novel fish breeding
      scheme, which is a combination of walk-back and optimum contribution selection
      using stochastic simulation. In this walk-back selection scheme, batches of
      different sizes (50, 100, 1,000, 5,000 and 10,000) with the phenotypically
      superior fish from one tank with mixed families were genotyped to set up the
      pedigree. BLUP estimated breeding values were calculated. The optimum
      contribution selection method was used with the rate of inbreeding (DeltaF)
      constrained to 0.005 or 0.01 per generation. If the constraint on DeltaF could
      not be held, a second batch of fish was genotyped etc. Compared with the
      genotyping of all selection candidates (1000, 5,000 or 10,000), the use of
      batches saves genotyping costs. The results show that two batches of 50 fish were
      often necessary. With a batch size of 100, genetic level was 76-92% of the
      genetic level achieved for schemes with all fish being genotyped and thus
      candidates for the optimum contribution selection step. More parents were
      selected for schemes with larger batches, resulting in a higher genetic gain,
      especially when all selection candidates were genotyped. There was little extra
      genetic gain in genotyping of 1,000 fish instead of 100 for the larger schemes of
      5,000 and 10,000 candidates. The accuracy of breeding values was similar for all
      batch sizes (approximately 0.30), but higher (approximately 0.5) when all
      candidates were included. Since only the phenotypically most superior fish were
      genotyped, BLUP-EBV were biased. Compared with genotyping of all selection
      candidates, the use of batches saves genotyping costs, while simultaneously
      maintaining high genetic gains.

PMID- 16277970
TI  - Power of QTL detection by either fixed or random models in half-sib designs.
AB  - The aim of this study was to compare the variance component approach for QTL
      linkage mapping in half-sib designs to the simple regression method. Empirical
      power was determined by Monte Carlo simulation in granddaughter designs. The
      factors studied (base values in parentheses) included the number of sires (5) and
      sons per sire (80), ratio of QTL variance to total genetic variance (lambda=
      0.1), marker spacing (10 cM), and QTL allele frequency (0.5). A single bi-allelic
      QTL and six equally spaced markers with six alleles each were simulated.
      Empirical power using the regression method was 0.80, 0.92 and 0.98 for 5, 10,
      and 20 sires, respectively, versus 0.88, 0.98 and 0.99 using the variance
      component method. Power was 0.74, 0.80, 0.93, and 0.95 using regression versus
      0.77, 0.88, 0.94, and 0.97 using the variance component method for QTL variance
      ratios (lambda) of 0.05, 0.1, 0.2, and 0.3, respectively. Power was 0.79, 0.85,
      0.80 and 0.87 using regression versus 0.80, 0.86, 0.88, and 0.85 using the
      variance component method for QTL allele frequencies of 0.1, 0.3, 0.5, and 0.8,
      respectively. The log10 of type I error profiles were quite flat at close marker
      spacing (1 cM), confirming the inability to fine-map QTL by linkage analysis in
      half-sib designs. The variance component method showed slightly more potential
      than the regression method in QTL mapping.

PMID- 16277972
TI  - Efficiency of population structures for mapping of Mendelian and imprinted
      quantitative trait loci in outbred pigs using variance component methods.
AB  - In a simulation study different designs for a pure line pig population were
      compared for efficiency of mapping QTL using the variance component method.
      Phenotypes affected by a Mendelian QTL, a paternally expressed QTL, a maternally
      expressed QTL or by a QTL without an effect were simulated. In all alternative
      designs 960 progeny were phenotyped. Given the limited number of animals there is
      an optimum between the number of families and the family size. Estimation of
      Mendelian and parentally expressed QTL is more efficient in a design with large
      family sizes. Too small a number of sires should be avoided to minimize chances
      of sires to be non-segregating. When a large number of families is used, the
      number of haplotypes increases which reduces the accuracy of estimating the QTL
      effect and thereby reduces the power to show a significant QTL and to correctly
      position the QTL. Dense maps allow for smaller family size due to exploitation of
      LD-information. Given the different possible modes of inheritance of the QTL
      using 8 to 16 boars, two litters per dam was optimal with respect to determining
      significance and correct location of the QTL for a data set consisting of 960
      progeny. The variance component method combining linkage disequilibrium and
      linkage analysis seems to be an appropriate choice to analyze data sets which
      vary in marker density and which contain complex family structures.

PMID- 16277973
TI  - The combined use of embryos and semen for cryogenic conservation of mammalian
      livestock genetic resources.
AB  - The objective of this empirical simulation study was to evaluate the use of a
      combination of semen and embryos in the creation of gene banks for reconstruction
      of an extinct breed. Such an approach was compared for banks with varying
      proportions of embryos on the basis of the amount of the material to be stored,
      time for reconstruction, maintenance of genetic variability, and probability of
      failure during reconstruction. Four types of populations were simulated, based on
      reproductive rate: single offspring, twinning, enhanced reproduction, and litter
      bearing. Reconstruction was simulated for banks consisting of different
      combinations of semen and reduced numbers of embryos (expressed as a percentage
      of the material needed for a bank containing exclusively embryos and ranging from
      10 to 90%). The use of a combination of semen and embryos increased the number of
      insemination cycles needed for reconstruction and the level of genetic
      relatedness in the reconstructed population. The risk for extinction was
      unacceptably high when a very low proportion of embryos (<20%) was used. However,
      combining semen with embryos could decrease costs, allowing for the conservation
      of more breeds, and specific strategies for semen use could decrease the level of
      relationships in the reconstructed breed.

PMID- 16277971
TI  - A simulation study for the analysis of uncertain binary responses: application to
      first insemination success in beef cattle.
AB  - A simulation was carried out to investigate the methods of analyzing uncertain
      binary responses for success or failure at first insemination. A linear mixed
      model that included, herd, year, and month of mating as fixed effects; and
      unrelated service sire, sire and residual as random effects was used to generate
      binary data. Binary responses were assigned using the difference between days to
      calving and average gestation length. Females deviating from average gestation
      length lead to uncertain binary responses. Thus, the methods investigated were
      the following: (1) a threshold model fitted to certain (no uncertainty) binary
      data (M1); (2) a threshold model fitted to uncertain binary data ignoring
      uncertainty (M2); and (3) analysis of uncertain binary data, accounting for
      uncertainty from day 16 to 26 (M3) or from day 14 to 28 (M4) after introduction
      of the bull, using a threshold model with fuzzy logic classification. There was
      virtually no difference between point estimates obtained from M1, M3, and M4 with
      true values. When uncertain binary data were analyzed ignoring uncertainty (M2),
      sire variance and heritability were underestimated by 22 and 24%, respectively.
      Thus, for noisy binary data, a threshold model contemplating uncertainty is
      needed to avoid bias when estimating genetic parameters.

PMID- 16277974
TI  - Identification of quantitative trait loci associated with bone traits and body
      weight in an F2 resource population of chickens.
AB  - Bone fractures at the end of lay are a significant problem in egg-laying strains
      of hens. The objective of the current study was to identify quantitative trait
      loci (QTL) associated with bone mineralization and strength in a chicken resource
      population. Layer (White Leghorn hens) and broiler (Cobb-Cobb roosters) lines
      were crossed to generate an F2 population of 508 hens over seven hatches, and 26
      traits related to bone integrity, including bone mineral density (BMD) and
      content (BMC), were measured. Genotypes of 120 microsatellite markers on 28
      autosomal groups were determined, and interval mapping was conducted to identify
      QTL regions. Twenty-three tests representing three chromosomal regions
      (chromosomes 4, 10 and 27) contained significant QTL that surpassed the 5% genome
      wise threshold, and 47 tests representing 15 chromosomes identified suggestive
      QTL that surpassed the 5% chromosome-wise threshold. Although no significant QTL
      influencing BMD and BMC were detected after adjusting for variation in body
      weight and egg production, multiple suggestive QTL were found. These results
      support previous experiments demonstrating an important genetic regulation of
      bone strength in chickens, but suggest the regulation may be due to the effects
      of multiple genes that each account for relatively small amounts of variation in
      bone strength.

PMID- 16277976
TI  - Interactions of amphipathic CPPs with model membranes.
AB  - We have investigated the interactions between two carrier peptides and model
      membrane systems as well as the conformational consequences of these
      interactions. Studies performed with lipid monolayers at the air-water interface
      have enabled identification of the nature of the lipid-peptide interactions and
      characterization of the influence of phospholipids on the ability of these
      peptides to penetrate into lipidic media. Penetration experiments reveal that
      both peptides interact strongly with phospholipids. Conformational investigations
      indicate that the lipid-peptide interaction govern the conformational state of
      the peptides. Based on the ability of both peptides to promote ion
      permeabilization of both natural and artificial membranes, we propose a model
      illustrating the translocation process. For MPG, it is based on the formation of
      a beta-barrel pore-like structure, while for Pep-1, it is based on association of
      helices.

PMID- 16277978
TI  - Identification and functional analysis of a novel bradykinin inhibitory peptide
      in the venoms of New World Crotalinae pit vipers.
AB  - A novel undecapeptide has been isolated and structurally characterized from the
      venoms of three species of New World pit vipers from the subfamily, Crotalinae.
      These include the Mexican moccasin (Agkistrodon bilineatus), the prairie
      rattlesnake (Crotalus viridis viridis), and the South American bushmaster
      (Lachesis muta). The peptide was purified from all three venoms using a
      combination of gel permeation chromatography and reverse-phase HPLC. Automated
      Edman degradation sequencing and MALDI-TOF mass spectrometry established its
      peptide primary structure as: Thr-Pro-Pro-Ala-Gly-Pro-Asp-Val-Gly-Pro-Arg-OH,
      with a non-protonated molecular mass of 1063.18 Da. A synthetic replicate of the
      peptide was found to be an antagonist of bradykinin action at the rat vascular B2
      receptor. This is the first bradykinin inhibitory peptide isolated from snake
      venom. Database searching revealed the peptide to be highly structurally related
      (10/11 residues) with a domain residing between the bradykinin-potentiating
      peptide and C-type natriuretic peptide domains of a recently cloned precursor
      from tropical rattlesnake (Crotalus durissus terrificus) venom gland. BIP thus
      represents a novel biological entity from snake venom.

PMID- 16277977
TI  - Monomeric G-protein, Rhes, is not an imidazoline-regulated protein in pancreatic
      beta-cells.
AB  - The monomeric G-protein, Rhes, is a candidate imidazoline-regulated molecule
      involved in mediating the insulin secretory response to efaroxan [S.L. Chan, L.K.
      Monks, H. Gao, P. Deaville, N.G. Morgan, Identification of the monomeric G
      protein, Rhes, as an efaroxan-regulated protein in the pancreatic beta-cell, Br.
      J. Pharmacol. 136 (1) (2002) 31-36]. This suggestion was based on observations
      regarding changes in Rhes mRNA expression in rat islets and pancreatic beta-cells
      after prolonged culture with efaroxan, leading to desensitization of the insulin
      response to the compound. To verify this report, we have evaluated the effects of
      the imidazoline compounds efaroxan and BL11282 on Rhes mRNA expression in
      isolated rat pancreatic islets maintained in conditions identical to those used
      by Chan et al. The results demonstrate that desensitization of the insulin
      response to efaroxan, or to another imidazoline, BL11282, does not change Rhes
      mRNA expression levels. Transfection of MIN6 cells with plasmids containing Rhes
      or Rhes-antisense also does not alter efaroxan- or BL11282-induced insulin
      secretion. Together, these data do not support the hypothesis that Rhes is an
      imidazoline-regulated protein.

PMID- 16277979
TI  - Extra domain A and type III connecting segment of fibronectin in assembly and
      cleavage.
AB  - To determine the role of the extra domain A (EDA) and type III connecting segment
      (IIICS) of fibronectin in fiber assembly, topographical distribution and
      proteolytic cleavage, eight full-length human fibronectin cDNA variants (aa0,
      aa64, aa89, and aa120 variations in the IIICS with or without the EDA) tagged
      with the V5 epitope were cloned from human endothelial cells and were expressed
      in CHO-K1 cells. All eight variants were assembled on cell surfaces. However,
      only the EDA(+) variants, regardless of the type of the IIICS domain, formed
      extensive fibrous networks. In contrast, the EDA(-)/aa64 and EDA(-)/aa89 variants
      were present predominantly as a soluble form. Western analysis of both soluble
      and cell-associated fibronectin/V5 variants showed that aa64, aa89, and aa120
      variants with or without the EDA domain produced the major 50- to 62-kDa C
      terminal fragments, whereas the aa0 variants did not, suggesting that the IIICS
      domain provides proteolytic cleavage sites.

PMID- 16277975
TI  - Alkaline pH homeostasis in bacteria: new insights.
AB  - The capacity of bacteria to survive and grow at alkaline pH values is of
      widespread importance in the epidemiology of pathogenic bacteria, in remediation
      and industrial settings, as well as in marine, plant-associated and extremely
      alkaline ecological niches. Alkali-tolerance and alkaliphily, in turn, strongly
      depend upon mechanisms for alkaline pH homeostasis, as shown in pH shift
      experiments and growth experiments in chemostats at different external pH values.
      Transcriptome and proteome analyses have recently complemented physiological and
      genetic studies, revealing numerous adaptations that contribute to alkaline pH
      homeostasis. These include elevated levels of transporters and enzymes that
      promote proton capture and retention (e.g., the ATP synthase and monovalent
      cation/proton antiporters), metabolic changes that lead to increased acid
      production, and changes in the cell surface layers that contribute to cytoplasmic
      proton retention. Targeted studies over the past decade have followed up the long
      recognized importance of monovalent cations in active pH homeostasis. These
      studies show the centrality of monovalent cation/proton antiporters in this
      process while microbial genomics provides information about the constellation of
      such antiporters in individual strains. A comprehensive phylogenetic analysis of
      both eukaryotic and prokaryotic genome databases has identified orthologs from
      bacteria to humans that allow better understanding of the specific functions and
      physiological roles of the antiporters. Detailed information about the properties
      of multiple antiporters in individual strains is starting to explain how specific
      monovalent cation/proton antiporters play dominant roles in alkaline pH
      homeostasis in cells that have several additional antiporters catalyzing
      ostensibly similar reactions. New insights into the pH-dependent Na(+)/H(+)
      antiporter NhaA that plays an important role in Escherichia coli have recently
      emerged from the determination of the structure of NhaA. This review highlights
      the approaches, major findings and unresolved problems in alkaline pH
      homeostasis, focusing on the small number of well-characterized alkali-tolerant
      and extremely alkaliphilic bacteria.

PMID- 16277980
TI  - Differential regulation of ionotropic glutamate receptor subunits following
      cocaine self-administration.
AB  - Previous examination of binge cocaine self-administration and 2 week withdrawal
      from cocaine self-administration on ionotropic glutamate receptor subunit
      (iGluRs) protein levels revealed significant alterations in iGluR protein levels
      that differed between the mesocorticolimbic and nigrostriatal pathways. The
      present study was undertaken to extend the examination of cocaine-induced
      alterations in iGluR protein expression by assessing the effects of acute
      withdrawal (15-16 h) from limited access cocaine self-administration (8 h/day, 15
      days). Western blotting was used to compare levels of iGluR protein expression
      (NR1-3B, GluR1-7, KA2) in the mesolimbic (ventral tegmental area, VTA; nucleus
      accumbens, NAc; and prefrontal cortex, PFC) and nigrostriatal pathways
      (substantia nigra, SN and dorsal caudate-putamen, CPu). Within the mesolimbic
      pathway, reductions were observed in NR1 and GluR5 immunoreactivity in the VTA
      although no significant alterations were observed in any iGluR subunits in the
      NAc. In the PFC, NR1 was significantly upregulated while GluR2/3, GluR4, GluR5,
      GluR6/7, and KA2 were decreased. Within the nigrostriatal pathway, NR1, NR2A,
      NR2B, GluR1, GluR6/7 and KA2 were increased in the dorsal CPu, whereas no
      significant changes were observed in the SN. The results demonstrate region- and
      pathway-specific alterations in iGluR subunit expression following limited
      cocaine self-administration and suggest the importance for the activation of
      pathways that are substrates of the reinforcing and motoric effects of cocaine.

PMID- 16277981
TI  - mummy/cystic encodes an enzyme required for chitin and glycan synthesis, involved
      in trachea, embryonic cuticle and CNS development--analysis of its role in
      Drosophila tracheal morphogenesis.
AB  - Tracheal and nervous system development are two model systems for the study of
      organogenesis in Drosophila. In two independent screens, we identified three
      alleles of a gene involved in tracheal, cuticle and CNS development. Here, we
      show that these alleles, and the previously identified cystic and mummy, all
      belong to the same complementation group. These are mutants of a gene encoding
      the UDP-N-acetylglucosamine diphosphorylase, an enzyme responsible for the
      production of UDP-N-acetylglucosamine, an important intermediate in chitin and
      glycan biosynthesis. cyst was originally singled out as a gene required for the
      regulation of tracheal tube diameter. We characterized the cyst/mmy tracheal
      phenotype and upon histological examination concluded that mmy mutant embryos
      lack chitin-containing structures, such as the procuticle at the epidermis and
      the taenidial folds in the tracheal lumen. While most of their tracheal
      morphogenesis defects can be attributed to the lack of chitin, when compared to
      krotzkopf verkehrt (kkv) chitin-synthase mutants, mmy mutants showed a stronger
      phenotype, suggesting that some of the mmy phenotypes, like the axon guidance
      defects, are chitin-independent. We discuss the implications of these new data in
      the mechanism of size control in the Drosophila trachea.

PMID- 16277982
TI  - Characterisation of Upd2, a Drosophila JAK/STAT pathway ligand.
AB  - The characterisation of ligands that activate the JAK/STAT pathway has the
      potential to throw light onto a comparatively poorly understood aspect of this
      important signal transduction cascade. Here, we describe our analysis of the only
      invertebrate JAK/STAT pathway ligands identified to date, the Drosophila unpaired
      like family. We show that upd2 is expressed in a pattern essentially identical to
      that of upd and demonstrate that the proteins encoded by this region activate
      JAK/STAT pathway signalling. Mutational analysis demonstrates a mutual semi
      redundancy that can be visualised in multiple tissues known to require JAK/STAT
      signalling. In order to better characterise the in vivo function of these
      ligands, we developed a reporter based on a natural JAK/STAT pathway responsive
      enhancer and show that ectopic upd2 expression can effectively activate the
      JAK/STAT pathway. While both Upd and Upd2 are secreted JAK/STAT pathway agonists,
      tissue culture assays show that the signal-sequences of Upd and Upd2 confer
      distinct properties, with Upd associated primarily with the extracellular matrix
      and Upd2 secreted into the media. The differing biophysical characteristics
      identified for Upd-like molecules have implications for their function in vivo
      and adds another aspect to our understanding of cytokine signalling in
      Drosophila.

PMID- 16277983
TI  - Molecular profiling of ulcerative colitis-associated neoplastic progression.
AB  - Fundamental differences exist between ulcerative colitis (UC)-associated and
      sporadic forms of colorectal cancer, including preexisting inflammation, type of
      dysplasia, and timing of molecular events in carcinogenesis. Transcriptional
      alterations that occur in UC-associated neoplasia in the progression from normal
      mucosa through dysplastic epithelium to invasive cancer have not been described.
      We used Affymetrix U95Av2 microarrays to assess differential gene expression in
      the neoplastic progression of UC tissue from the colonic mucosa of individuals
      with benign UC, UC-dysplasia-associated lesions or masses, and UC adenocarcinoma.
      By correlating transcript alterations across tissue types using a mixed
      statistical model, we identified 699 genes exhibiting altered expression with
      dysplasia development. A different expression profile was observed in progression
      to adenocarcinoma with 392 transcripts exhibiting differential expression. There
      were 224 transcripts common to both dysplasia and adenocarcinoma. Most of the
      differentially expressed genes described herein were not previously known to play
      a role in neoplastic progression in UC, including transcripts affecting cell
      proliferation and apoptosis, signal transduction and signaling, and DNA repair.
      The altered expression of five transcripts was confirmed by quantitative real
      time reverse-transcription polymerase chain reaction. Based on comparisons with
      previous studies on sporadic colorectal carcinoma, several similarities were
      found. There were, however, important differences that suggest that different
      molecular events may occur in the development of UC-associated neoplasia. Several
      of these genes demonstrated similar changes in dysplastic and cancerous tissue
      and may be involved in early cancer formation. Identification of these genes as
      potential clinical biomarkers may lead to improved early disease diagnosis.

PMID- 16277984
TI  - Hypothalamic GnRH-I and its precursor during photorefractoriness onset in free
      living male Dark-eyed Juncos (Junco hyemalis) of different year classes.
AB  - The termination of seasonal breeding in most photoperiodic passerines is heralded
      by spontaneous gonadal regression as a result of long day exposure. This
      phenomenon is termed absolute photorefractoriness and this insensitivity to long
      days may only be dissipated by short photoperiod exposure. The timing of the
      transition to a photorefractory stage in adult free-living male Dark-eyed Juncos
      is age-dependent. Second-year males (SY, entering their first breeding season)
      molt earlier, suggesting that they become refractory earlier, than older males
      (ASY). We determined whether the earlier onset of photorefractoriness in SY males
      concurs with decreased expression of hypothalamic GnRH-I or its precursor, pro
      GnRH-GAP. Male SY and ASY juncos were caught at the end of the breeding season
      either during, or following, testicular regression. Immunoreactivity for GnRH-I
      and pro-GnRH-GAP was found in perikarya in the preoptic area, and fibers in the
      median eminence. The number and size of cells immunoreactive for GnRH-I and pro
      GnRH-GAP did not significantly differ with age or time of year. In ASY juncos,
      there was a significant decrease in both GnRH-I and pro-GnRH-GAP staining density
      at the median eminence following testicular regression at a time of
      photorefractoriness onset. Density of pro-GnRH-GAP at the median eminence was
      also reduced following testicular regression in SY males but GnRH-I staining
      density did not change. Thus, age-class differences in the transition to
      photorefractoriness do not appear to result from differences in GnRH-I synthesis.
      Instead, the regulation of GnRH-I secretion by non-photoperiodic factors may
      determine photorefractoriness onset.

PMID- 16277985
TI  - Time keeping by the quail's eye: circadian regulation of melatonin production.
AB  - Previous studies have shown that eye removal disrupts the circadian body
      temperature and activity rhythms of Japanese quail supporting the hypothesis that
      the eyes act as pacemakers within the quail circadian system. Furthermore, the
      putative ocular pacemakers are coupled to the rest of the circadian system via
      neural and hormonal outputs. Although the neural pathway has yet to be
      identified, experiments suggest that the daily rhythm of ocular melatonin
      synthesis and release is the hormonal output. We sought to strengthen the
      hypothesis that the eyes are the loci of circadian pacemakers, and that melatonin
      output is involved, by examining melatonin secretion in cultured quail retinas.
      Using an in vitro flow-through system we demonstrated that (1) isolated retinal
      tissue could exhibit a rhythm of melatonin release, (2) the rhythm of melatonin
      synthesis is directly entrainable by 24-h light-dark cycles, and (3)
      supplementation of the culture medium with serotonin is necessary for robust,
      rhythmic production of melatonin in constant darkness. These results show
      definitively that the eyes are the loci of a biological clock and, in light of
      previous studies showing the disruptive effects of blinding on the circadian
      system, strengthen the hypothesis that the ocular clock is a circadian pacemaker
      that can affect the rest of the circadian system via the cyclic synthesis and
      release of melatonin. The quail retina is proving to be a valuable in vitro model
      for investigating properties of circadian pacemakers.

PMID- 16277986
TI  - Hormonal state influences aspects of female mate choice in the Tungara Frog
      (Physalaemus pustulosus).
AB  - Females alter their mate choices as they transition through different
      reproductive stages; however, the proximal mechanisms for such behavioral
      fluctuation are unclear. In many taxa, as females transition through different
      reproductive stages, there is an associated change in hormone levels; therefore,
      we examined whether fluctuation in hormone levels serves as a proximal mechanism
      for within-individual variation in mate choice in female tungara frogs
      (Physalaemus pustulosus). We manipulated hormone levels of females by
      administering 0, 10, 100, 500 or 1,000 IU of human chorionic gonadotropin (HCG),
      which is a ligand for luteinizing hormone (LH) receptors and will therefore cause
      increased gonadal hormone production. Phonotaxis assays were conducted to measure
      three aspects of mate choice behavior before and after HCG administration;
      receptivity (response to a conspecific mate signal), permissiveness (response to
      a signal that is less attractive than conspecific signals) and discrimination
      (ability to discern signal differences). The probability of response to a
      conspecific and an artificial hybrid signal significantly increased at the
      highest HCG doses. The difference in mean response time between pre- and post-HCG
      tests was significantly different for both the receptivity and permissiveness
      tests among the five doses. Increased permissiveness, however, was not due to
      decreased discrimination because females could discriminate between calls even at
      the highest HCG doses. These hormonal manipulations caused the same behavioral
      pattern we reported in females as they transitioned through different
      reproductive stages (Lynch, K.S., Rand, A.S., Ryan, M.J., Wilczynski, W., 2005.
      Plasticity in female mate choice associated with changing reproductive states.
      Anim. Behav. 69, 689-699), suggesting that changes in hormone levels can
      influence the female's mate choice behavior.

PMID- 16277987
TI  - The penetration of a soft solid by a liquid jet, with application to the
      administration of a needle-free injection.
AB  - Liquid jet injections have been performed on human skin in vivo and silicone
      rubber using Intraject needle-free injectors. The discharge characteristics of
      the liquid jet were measured using a custom-built test instrument. The
      experiments reveal that a high-speed liquid jet penetrates a soft solid by the
      formation and opening of a planar crack. The fluid stagnation pressure required
      for skin penetration decreases with increasing diameter of the liquid jet. These
      findings are consistent with the slow-speed penetration of a soft solid by a
      sharp-tipped punch. It is demonstrated that the Shergold-Fleck sharp-tipped punch
      penetration model [Shergold, O.A., Fleck, N.A., 2004. Mechanisms of deep
      penetration of soft solids. Proc. Roy. Soc. Lond. A 460, 3037-3058.] gives
      adequate predictions for the pressure required to penetrate a soft solid by a
      high-speed liquid jet.

PMID- 16277988
TI  - Multivalent display system on filamentous bacteriophage pVII minor coat protein.
AB  - The systems for display of foreign peptides and polypeptides on filamentous
      bacteriophage have exploited genetic fusion to all of the five coat proteins.
      Multivalent display systems allowing selection of low affinity antibody fragments
      have been devised for fusions to gene III. However, since pIII has to interact
      with the bacterial receptors during the infection process, reduced infectivity
      can be observed. Alternative display systems utilizing other coat protein have
      been examined. These, however, take advantage of phagemid systems, in which a
      mixture of fusion and non-fusion coat proteins becomes displayed, thus preventing
      multivalent display. In this paper, we describe genetically stable fusion of scFv
      fragments to gene VII directly in the phage genome, thus giving rise to a
      multivalent display system where infectivity is not comprised. A hundred-fold
      enrichments factor can be obtained in model selection. Our results demonstrate
      that the small size of pVII (33 amino acids) is not structurally compromised by
      fusion of scFv antibody fragments at their N-terminus, thus demonstrating the
      feasibility of utilizing pVII as a fusion partner.

PMID- 16277989
TI  - One-step immunostrip test for the simultaneous detection of free and total
      prostate specific antigen in serum.
AB  - The development of a one-step lateral flow immunoassay on a strip format for the
      rapid and reliable simultaneous detection of serum levels of free and total
      prostate specific antigen (f-PSA and t-PSA) and estimation of f-PSA to t-PSA
      ratio (f/t-PSA) is reported. The f/t-PSA ratio has shown to be more specific for
      the correct diagnosis of prostate cancer than t-PSA alone, especially in the so
      called diagnostic grey zone of 4-10 microg/l t-PSA. The performance of the system
      described relied on non-competitive immunoassay protocols. Herein, f-PSA and t
      PSA were sandwiched between anti-f-PSA and anti-t-PSA monoclonal antibodies
      immobilised on the strip and a colloidal gold anti-PSA antibody tracer. In the
      presence of PSA in the sample, the tracer accumulated on the strip results in the
      appearance of specific pink colour lines. The colour intensity of these lines was
      found to be directly proportional to the PSA concentration and a semi
      quantitative estimation could be carried out visually. Quantitative analysis was
      also possible by densitometry. Using PSA standards prepared in female serum, the
      strip could be calibrated up to a concentration of 60 microg/l for both PSA
      species, with an assay time of less than 20 min. The estimated detection limit
      was 1 microg/l in all cases. The immunostrip showed good storage stability for at
      least 2 months and the reproducibility was always between 12% and 17%. Fifty-one
      male serum samples were analysed with the strip and results compared with values
      obtained by two different commercial immunoassays taken as reference methods. The
      study yielded acceptable correlation and agreement. An estimation of the
      sensitivity and specificity demonstrated the strip validity as a potential front
      line device for the early detection of prostate cancer and differentiation of
      benign prostatic anomalies. Small plastic cartridges incorporating the
      immunostrip and a small blister containing washing solution that helps remove
      unbound species from the strip were envisaged in order to avoid false positive
      readings and decrease background signals, thereby leading to better sensitivity
      and detection limits.

PMID- 16277990
TI  - Interstrand pairing patterns in beta-barrel membrane proteins: the positive
      outside rule, aromatic rescue, and strand registration prediction.
AB  - beta-Barrel membrane proteins are found in the outer membrane of Gram-negative
      bacteria, mitochondria, and chloroplasts. Little is known about how residues in
      membrane beta-barrels interact preferentially with other residues on adjacent
      strands. We have developed probabilistic models to quantify propensities of
      residues for different spatial locations and for interstrand pairwise contact
      interactions involving strong H-bonds, side-chain interactions, and weak H-bonds.
      Using the reference state of exhaustive permutation of residues within the same
      beta-strand, the propensity values and p-values measuring statistical
      significance are calculated exactly by analytical formulae we have developed. Our
      findings show that there are characteristic preferences of residues for different
      membrane locations. Contrary to the "positive-inside" rule for helical membrane
      proteins, beta-barrel membrane proteins follow a significant albeit weaker
      "positive-outside" rule, in that the basic residues Arg and Lys are
      disproportionately favored in the extracellular cap region and disfavored in the
      periplasmic cap region. We find that different residue pairs prefer strong
      backbone H-bonded interstrand pairings (e.g. Gly-aromatic) or non-H-bonded
      pairings (e.g. aromatic-aromatic). In addition, we find that Tyr and Phe
      participate in aromatic rescue by shielding Gly from polar environments. We also
      show that these propensities can be used to predict the registration of strand
      pairs, an important task for the structure prediction of beta-barrel membrane
      proteins. Our accuracy of 44% is considerably better than random (7%). It also
      significantly outperforms a comparable registration prediction for soluble beta
      sheets under similar conditions. Our results imply several experiments that can
      help to elucidate the mechanisms of in vitro and in vivo folding of beta-barrel
      membrane proteins. The propensity scales developed in this study will also be
      useful for computational structure prediction and for folding simulations.

PMID- 16277991
TI  - Polyglutamine is not all: the functional role of the AXH domain in the ataxin-1
      protein.
AB  - A family of neurodegenerative diseases is associated with anomalous expansion of
      a polyglutamine tract in the coding region of the corresponding proteins. The
      current working hypothesis is that polyglutamine diseases are caused by
      misfolding and aggregation of the proteins with a process dictated by the
      polyglutamine tracts, although increasing evidence suggests an involvement of the
      protein context in modulating these properties. Here, we show that the AXH domain
      of ataxin-1, the protein involved in spinocerebellar ataxia type-1, is the region
      responsible for the transcriptional repression activity of ataxin-1 and
      participates in protein aggregation. In vitro, the isolated domain undergoes a
      conformational transition towards a beta-enriched structure associated with
      aggregation and amyloid fibre formation spontaneously and without need for
      destabilizing conditions. Using a transfected cell line, we demonstrate that,
      while determined by polyglutamine expansion, ataxin-1 aggregation is noticeably
      reduced by deletion of AXH or by replacement with the homologous sequence from
      the transcription factor HBP1, which has no known tendency to aggregate. These
      results provide the first direct evidence of an involvement of a region other
      than the polyglutamine tract in polyglutamine pathologies.

PMID- 16277992
TI  - Kinetic, stability, and structural changes in high-resolution crystal structures
      of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S.
AB  - The crystal structures, dimer stabilities, and kinetics have been analyzed for
      wild-type human immunodeficiency virus type 1 (HIV-1) protease (PR) and resistant
      mutants PR(L24I), PR(I50V), and PR(G73S) to gain insight into the molecular basis
      of drug resistance. The mutations lie in different structural regions. Mutation
      I50V alters a residue in the flexible flap that interacts with the inhibitor,
      L24I alters a residue adjacent to the catalytic Asp25, and G73S lies at the
      protein surface far from the inhibitor-binding site. PR(L24I) and PR(I50V),
      showed a 4% and 18% lower k(cat)/K(m), respectively, relative to PR. The relative
      k(cat)/K(m) of PR(G73S) varied from 14% to 400% when assayed using different
      substrates. Inhibition constants (K(i)) of the antiviral drug indinavir for the
      reaction catalyzed by the mutant enzymes were about threefold and 50-fold higher
      for PR(L24I) and PR(I50V), respectively, relative to PR and PR(G73S). The dimer
      dissociation constant (K(d)) was estimated to be approximately 20 nM for both
      PR(L24I) and PR(I50V), and below 5 nM for PR(G73S) and PR. Crystal structures of
      the mutants PR(L24I), PR(I50V) and PR(G73S) were determined in complexes with
      indinavir, or the p2/NC substrate analog at resolutions of 1.10-1.50 Angstrom.
      Each mutant revealed distinct structural changes relative to PR. The mutated
      residues in PR(L24I) and PR(I50V) had reduced intersubunit contacts, consistent
      with the increased K(d) for dimer dissociation. Relative to PR, PR(I50V) had
      fewer interactions of Val50 with inhibitors, in agreement with the dramatically
      increased K(i). The distal mutation G73S introduced new hydrogen bond
      interactions that can transmit changes to the substrate-binding site and alter
      catalytic activity. Therefore, the structural alterations observed for drug
      resistant mutations were in agreement with kinetic and stability changes.

PMID- 16277993
TI  - Cross-cultural adaptation and validation of multiple sclerosis quality of life
      questionnaire (MSQOL-54) in a Turkish multiple sclerosis sample.
AB  - OBJECTIVE: Multiple sclerosis (MS) is a chronic progressive disease with multiple
      neurological impairments. The disease can also dramatically affect the health
      related quality of life of patients. The objective of this study was to
      investigate the validation of the translated and cross-culturally adapted MSQOL
      54 in 183 Turkish MS patients. METHODS: 183 adults classified as having definite
      MS patients were enrolled into the study. Patients were classified into four
      severity groups according to the expanded disability status scale (EDSS); group I
      (EDSS 0-4), group II (EDSS 4.5-5.5), group III (EDSS 6-6.5) and group IV (EDSS 7
      8). MSQOL-54 questionnaire were translated and culturally adapted into Turkish.
      Associations between age, gender, disease duration, EDSS score, marital status,
      education and health insurance and the MSQOL-54 physical and mental health
      composite scores were determined. RESULTS: The mean age of the 183 patients (138
      female and 45 male) was 39+/-10 years. The questionnaire was well accepted but
      small cultural adaptations were required. EDSS scores showed significant
      associations with the MSQOL-54 physical and mental health composite scores. From
      the different EDSS groups only, the group I (EDSS 0-4) score was significantly
      associated with the physical health composite as well as the disease duration
      showed significant correlation with the physical and mental composite scores.
      None of the other EDSS groups and the other parameters showed correlation with
      physical health composite or mental health composite. CONCLUSION: Assessment of
      quality of life of MS patients in addition to disease severity and disability
      level is important, because it provides unique information that is important to
      patients and to clinicians. A translation of an existing MS-targeted HRQOL
      measure from US English into Turkish was easily administered and well accepted in
      a Turkish MS sample.

PMID- 16277994
TI  - Dynamics of prey-flock escaping behavior in response to predator's attack.
AB  - The dynamic behavior of prey-flock in response to predator's attack was
      investigated by using molecular dynamics (MD) simulations in a two-dimensional
      (2D) continuum model. By locally applying interactive forces between prey
      individuals (e.g. attraction, repulsion, and alignment), a coherently moving
      state in the same direction was obtained among individuals in prey-flock. When a
      single predator was introduced to the prey population, the prey-flock was
      correspondingly deformed by the predator's continuous attacks towards the prey
      flock's center. In response to the predator's attack, three regimes in the flock
      size (compression (Regime I), expansion (Regime II), compression (Regime III))
      were revealed if the predator's attack speed (kappa) was comparatively low to the
      escape speed of prey-flock. If noise was added to the predator's attacking
      course, a higher degree of variation was observed in the patterns of compression
      and expansion in the prey-flock size. However, the scaling behavior in the
      changes in prey-flock size was present in different levels of noise with the
      increase in predation risk (R) when kappa takes an appropriately low value.
      During the procedure of escaping, order breaking in alignment (phi) of prey
      population was observed, while the degree of alignment was dependent upon the
      changes in parameters of kappa and R.

PMID- 16277995
TI  - Curvature-induced accumulation of anisotropic membrane components and raft
      formation in cylindrical membrane protrusions.
AB  - Coupling between the area density of anisotropic membrane inclusions and local
      membrane curvature is considered theoretically for a simple case of nearly flat
      bilayer membrane with thin tubular membrane protrusions. Lateral phase
      separation, i.e. accumulation of membrane inclusions in tubular membrane
      protrusions was obtained for strongly anisotropic inclusions if the radius of
      tubular protrusions is small enough. In accordance with these theoretical
      predictions we observed persistence of long tubular membrane protrusions devoid
      of internal rod-like microtubular structure in cells. We suggest that the
      stability of the tubular membrane protrusions without the inner supporting rod
      like cytoskeleton is a consequence of the accumulation of anisotropic membrane
      components in the bilayer membrane of these protrusions. Based on the presented
      theoretical and experimental results it is suggested that previously reported
      concentration of prominin rafts in thin tubular membrane protrusions may be
      caused by a curvature-induced accumulation of small prominin-lipid complexes
      (inclusions) in protrusions and their coalescence into larger rafts.

PMID- 16277996
TI  - Information catastrophe in RNA viruses through replication thresholds.
AB  - RNA viruses are known to replicate at very high mutation rates. These rates are
      actually known to be close to their so-called error threshold. This threshold is
      in fact a critical point beyond which genetic information is lost through a so
      called error catastrophe. However, the transition from a stable quasispecies to
      genetic drift and loss of information can also occur by crossing replication
      thresholds, below some replication rates, the viral population is suddenly unable
      to survive. Available data from hepatitis C virus population analysis [Mas, A.,
      Ulloa, E., Bruguera, M., Furcic, I., Garriga, D., Fabregas, S., Andreu, D., Saiz,
      J.C., Diez, J., 2004. Hepatitis C virus population analysis of a single-source
      nosocomial outbreak reveals an inverse correlation between viral load and
      quasispecies complexity. J. Gen. Virol. 85, 3619-3626] can be interpreted through
      this theoretical view, providing evidence for such a replication threshold. Here
      a simple model is used in order to provide evidence for such a phenomenon,
      consistent with available data.

PMID- 16277997
TI  - Caffeic acid phenethyl ester ameliorates changes in IGFs secretion and gene
      expression in streptozotocin-induced diabetic rats.
AB  - The protective effect of caffeic acid phenethyl ester (CAPE) against diabetes
      induced alteration of IGFs protein and gene expression was investigated in serum,
      liver, heart, and kidney. In the present study, diabetic rats exhibited the
      decrease of IGF-I content in serum, liver and heart but the increase of that in
      kidney and CAPE blocked them. Diabetic rats also manifested the increase of IGF
      II content in serum, liver, heart, and kidney and CAPE prevented them. CAPE
      prevented the diabetes-induced decrease of liver IGF-I mRNA and IGF-II mRNA,
      which is similar to pattern of IGFs mRNA in kidney. Moreover, diabetic rats
      exhibited the decrease of heart IGF-I mRNA but the increase of IGF-II mRNA and
      CAPE blocked them. In conclusion, CAPE, in part, prevented diabetes-induced
      alteration of IGF-I and IGF-II protein and gene expression in liver, heart, and
      kidney in rats.

PMID- 16277998
TI  - Parieto-frontal interactions, personal space, and defensive behavior.
AB  - In the monkey brain, two interconnected cortical areas have distinctive neuronal
      responses to visual, tactile, and auditory stimuli. These areas are the ventral
      intraparietal area (VIP) and a polysensory zone in the precentral gyrus (PZ). The
      multimodal neurons in these areas typically respond to objects touching, near, or
      looming toward the body surface. Electrical stimulation of these areas evokes
      defensive-like withdrawing or blocking movements. These areas have been suggested
      to participate in a range of functions including navigation by optic flow,
      attention to nearby space, and the processing of object location for the guidance
      of movement. We suggest that a major emphasis of these areas is the construction
      of a margin of safety around the body and the selection and coordination of
      defensive behavior. In this review, we summarize the physiological properties of
      these brain areas and discuss a range of behavioral phenomena that might be
      served by those neuronal properties, including the ducking and blocking reactions
      that follow startle, the flight zone of animals, the personal space of humans,
      the nearby, multimodal attentional space that has been studied in humans, the
      withdrawal reaction to looming visual stimuli, and the avoidance of obstacles
      during self-motion such as locomotion or reaching.

PMID- 16277999
TI  - Metabolic effects of green tea and of phases of weight loss.
AB  - The effect of ingestion of green tea (GT) extract along with a low-energy diet
      (LED) on health-related blood parameters, and the relationships among changes in
      metabolic parameters and phases of weight loss were assessed. A double-blind,
      placebo-controlled, parallel design was used. 46 female subjects (BMI 27.7+/-1.8
      kg/m(2)) were fed in energy balance from days 1 to 3, followed by a LED with GT
      (n=23) or placebo (PLAC, n=23) from days 4 to 87. The LED-period consisted of a
      phase 1 of 4 weeks (days 4-32) followed by a phase 2 of 8 weeks (days 32-87).
      Body composition and fasting blood samples were determined on days 4, 32 and 87.
      No significant differences were observed between the blood parameters of the PLAC
      and GT group. In phase 1 compared to phase 2 the rate of weight loss was 0.09+/
      0.05 kg/day vs. 0.03+/-0.03 kg/day (p<0.001); Fat free mass (FFM) was 21% of
      weight loss in phase 1 vs. 7% in phase 2 (ns). Surprisingly, favourable changes
      in free fatty acids, triacylglycerol, beta-hydroxybutyrate, glucose and total
      cholesterol in phase 1 were reversed in phase 2 (p<0.01). Taken together, GT
      supplementation during a LED had no effect on health-related blood parameters.
      Initial improvements in several blood measures at day 32 were reversed by day 87,
      despite continued weight loss. Modest weight loss improved HDL cholesterol and
      blood pressure.

PMID- 16278000
TI  - Revisiting the liver in human yellow fever: virus-induced apoptosis in
      hepatocytes associated with TGF-beta, TNF-alpha and NK cells activity.
AB  - Flavivirus infection as dengue and yellow fever persists as a terrible menace to
      pandemics, due to Aedes prevalence in the Americas. Yellow fever is characterized
      by hepatocyte damage, with steatosis, apoptosis and necrosis, mainly in the
      midzonal region of the liver, but the injury mechanism has not been studied at
      the light of recent knowledge, such as the advances in cell death mechanisms,
      inflammatory response and cytokine cell expression tools. We studied 53 human
      liver paraffin embedded blocks from patients who died with yellow fever, all with
      histological demonstration of higher prevalence of apoptosis over necrosis and
      mild disproportionate inflammatory response. Viral antigens were found most
      frequently in hepatocytes from the midzonal area than other lobule areas, as
      detected by specific immunohistochemistry. Infiltrating cell subpopulations
      showed mainly CD4+ T lymphocytes, with small numbers of CD8+ cytotoxic
      lymphocytes, CD20+ B lymphocytes, NKT+ cells and S100+ dendritic cells in the
      sites of inflammation, as compared to normal and leptospirosis liver blocks. Some
      cells expressed TNF-alpha and IFN-gamma, but a much more intense proportion of
      TGF-beta expressing cells were found, suggesting both a Th1 and Th3 patterns of
      immune response in yellow fever. Most affected hepatocyte presented apoptosis
      markers that appear at the cell death main pathway in this infection. Viral
      antigens, which production could interfere in hepatocyte biology, could induce
      the activation of apoptosis cascade, but TGF-beta was also an apoptosis promoter.
      Our finding supports the key effect of the yellow fever virus in hepatocyte
      injury, resulting in prevalence of apoptosis over necrosis, aside from a TGF-beta
      action induced by the inflammatory response.

PMID- 16278001
TI  - HIV-infected cells are major inducers of plasmacytoid dendritic cell interferon
      production, maturation, and migration.
AB  - Plasmacytoid dendritic cells (PDC), natural type-1 interferon (IFN) producing
      cells, could play a role in the innate anti-HIV immune response. Previous reports
      indicated that PDC IFN production is induced by HIV. Our results show a more
      robust IFN induction when purified PDC (>95%) were exposed to HIV-infected cells.
      This effect was not observed with non-viable cells, DNA, and RNA extracted from
      infected cells, and viral proteins. The response was blocked by anti-CD4 and
      neutralizing anti-gp120 antibodies as well as soluble CD4. IFN induction by HIV
      infected cells was also prevented by low-dose chloroquine, which inhibits
      endosomal acidification. PDC IFN release resulted in reduced HIV production by
      infected CD4+ cells, supporting an anti-HIV activity of PDC. Stimulated CD4+
      cells induced PDC activation and maturation; markers for PDC migration (CCR7)
      were enhanced by HIV-infected CD4+ cells only. This latter finding could explain
      the decline in circulating PDC in HIV-infected individuals.

PMID- 16278002
TI  - Evaluation of quantitative real time PCR for the measurement of Helicobacter
      pylori at low concentrations in drinking water.
AB  - A rapid DNA extraction and quantitative, real time polymerase chain reaction
      (QRTPCR) analysis method targeting the ureA gene of Helicobacter pylori was
      evaluated for the measurement of these organisms on membrane filters at levels
      that might be expected to be found in drinking water samples. No interference was
      seen from high levels of background organisms and related, non-target species
      were detected at approximately 4-5 log(10) lower levels of sensitivity than H.
      pylori by this assay. A standard curve was generated for the method from analyses
      of filters containing known numbers of added H. pylori cells. Cell numbers on
      these filters were determined by staining with a species-specific fluorescent
      antibody and solid phase cytometry analyses. The mean detection sensitivity of
      the method was 10 H. pylori cells per filter with a 95% confidence sensitivity of
      40 cells and a 95% confidence precision interval of +/-0.57 log(10) based on
      duplicate analyses of the samples. One liter drinking water samples from several
      locations in the US were inoculated with the same H. pylori cell suspensions used
      to generate the standard curve and gave measurements that were consistent with
      the standard curve suggesting that these sample matrices produced no interference
      in the method. This method may be useful for the rapid screening of drinking
      water for H. pylori.

PMID- 16278003
TI  - Nitrogen and phosphorus removal from an abattoir wastewater in a SBR with aerobic
      granular sludge.
AB  - The formation and performance of granular sludge was studied in an 8l sequencing
      batch reactor (SBR) treating an abattoir (slaughterhouse) wastewater. Influent
      concentrations averaged 1,520 mg l(-1) volatile suspended solids (VSS), 7,685 mg
      l(-1) Chemical oxygen demand (COD), 1,057 mg l(-1) total kjeldahl nitrogen (TKN),
      217 mg l(-1) total P. The COD loading was 2.6 kgm(-3)d(-1). The SBR was seeded
      with flocculating sludge from a SBR with an 1h settle time, but granules
      developed within 4 days by reducing the settle time to 2 min. The SBR cycle also
      had 120 min mixed (anaerobic) fill, 220 min aerated react, and 18 min draw/idle.
      The granules had a mean diameter of 1.7 mm, a specific gravity of 1.035, a
      density of 62 g VSS l(-1), a zone settling velocity (ZSV) of 51 mh(-1), and a
      sludge volume index (SVI) of 22 ml g(-1). Without optimizing process conditions,
      removal of COD and P were over 98%, and removal of N and VSS were over 97%.
      Nitrification and denitrification occurred simultaneously during react. The
      results indicate that conventional SBRs treating wastewaters with flocculating
      sludge can be converted to granular SBRs by reducing the settle time.

PMID- 16278004
TI  - Effect of heat recovery from raw wastewater on nitrification and nitrogen removal
      in activated sludge plants.
AB  - By recovery of heat from the raw wastewater in the sewer system, the influent
      temperature of a wastewater treatment plant (WWTP) is reduced. This can have a
      negative effect on nitrification in the WWTP, since this process strongly depends
      on temperature. The analysis of the temperature regime in the WWTP of Zurich,
      Switzerland, revealed that in the cold season, the effluent temperature is about
      0.7 degrees C higher than the influent temperature and that nitrification is not
      affected by a decrease of the influent wastewater temperature lasting for a
      couple of hours only, but is significantly affected by a longer lasting
      temperature decrease. Three diagrams were developed with a steady-state model,
      from which the consequences of a permanent temperature decrease on the
      nitrification safety factor, aerobic sludge retention time and total nitrogen
      removal can be evaluated. Using simulations with a dynamic model, calibrated for
      the Zurich WWTP, a quantitative relationship between the wastewater temperature
      and the ammonium effluent concentration was established. This relationship can,
      in combination with measured effluent concentrations of an existing WWTP, be used
      to predict the increase of the ammonium effluent concentration in this plant
      resulting from a permanent decrease of the wastewater influent temperature.

PMID- 16278005
TI  - Application of microwaves for sewage sludge conditioning.
AB  - The article focuses on the effect of microwave treatment on the de-waterability
      of sewage sludge. The specific resistance to filtration, capillary suction time,
      and dry matter content in centrifuged sludge cake were measured. The quality of
      sludge liquor obtained after microwave processing was also analysed. It was found
      out that microwaves improve sludge de-waterability. The quantitative improvement
      depends on sludge type-better effect of microwave processing were observed in the
      primary sludge compared to mixed or digested sludges. If microwave treatment is
      followed by polyelectrolyte conditioning, the effects are considerably better
      than while these conditioning methods are used separately. Microwave conditioning
      increased burden of organic matter (BOD(5), COD) in the sludge liquor.

PMID- 16278006
TI  - Application of commercial biochemical oxygen demand inocula for biodegradable
      dissolved organic carbon determination.
AB  - Biochemical oxygen demand (BOD) and biodegradable dissolved organic carbon (BDOC)
      measure the amount of biodegradable organics in water samples using mixed culture
      seeds. The BOD method relies on the dissolved oxygen reduction while the BDOC
      procedure, which is more novel, is based on the dissolved organic carbon decrease
      during the incubation. In this study, three commercial BOD seeds, namely BOD
      Seed, Bi-Chem and Polyseed, were tested as inocula for BDOC measurement. Standard
      solutions, secondary effluent and raw surface water samples were used. BDOC
      exertions provided by the commercial seeds were compared with those obtained from
      two existing BDOC inocula, indigenous and mixed liquor suspended solid (MLSS)
      seeds. The commercial and indigenous inocula provided similar exertion trends and
      BDOC results that were not significantly different for surface water samples
      while the results for secondary effluent samples were inconclusive. The MLSS
      inoculum tend to provide slightly higher BDOC values and faster exertion kinetics
      than the commercial and indigenous inocula. The exertions by all five inocula
      could be expressed well with first-order kinetics for all cases that enough data
      were available for kinetics evaluation. The commercial seeds were similar in
      terms of BDOC determination accuracy and precision, and exertion kinetics. It is
      possible to use the commercial BOD inocula as seeds for BDOC determination but
      the results might not be statistically the same as those of the indigenous
      inoculum for certain types of samples.

PMID- 16278007
TI  - Treatment of Alzheimer's disease: from pharmacology to a better understanding of
      disease pathophysiology.
AB  - Alzheimer's disease (AD) is the most common cause of cognitive impairment in
      older patients and is expected to increase greatly in prevalence in the next
      future. It is characterized by the development of senile plaques and
      neurofibrillary tangles, which are associated with neuronal loss affecting to a
      greater extent cholinergic neurons. A cascade of pathophysiological events is
      triggered in AD that ultimately involves common cellular signalling pathways and
      leads to cellular and neural networks dysfunction, failure of neurotransmission,
      cell death and a common clinical outcome. The process is asynchronous and viable
      neurons remain an important target for therapeutic intervention at each stage of
      disease evolution. At present symptomatic drugs inhibiting the degradation of
      acetylcholine within synapses and more recently glutamate receptor antagonists
      represent the mainstay of therapy. However, interventions able to halt or slow
      disease progression (i.e., disease-modifying agents) are necessary. Although much
      progress has been made in this area, there are currently no clinically approved
      interventions for AD classed as disease modifying or neuroprotective. This paper
      reviews the main symptomatic strategies available for treating AD and future
      strategies for improving our therapeutic approach to AD.

PMID- 16278008
TI  - PCDD/F and PCB concentrations in Arctic ringed seals (Phoca hispida) have not
      changed between 1981 and 2000.
AB  - Concentrations of polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans
      (PCDF) and of non-ortho-, mono-ortho- and di-ortho-substituted polychlorinated
      biphenyls (NO-CB, MO-CB and DO-CB) were measured in blubber of ringed seals
      sampled at Holman, NWT, in 1981, 1991, 1996 and 2000. Total PCDD and PCDF
      concentrations were usually below approx. 10 and 5 pg/g wet wt., respectively,
      and did not change significantly between 1981 and 2000, although there were
      sporadic temporal differences in some congeners. Total NO-CB, MO-CB and DO-CB
      concentrations were below approx. 1 ng/g, 250 ng/g and 1 microg/g wet wt.
      respectively; none of the total PCB concentrations changed significantly over the
      sampling period. Neither PCDD nor PCDF concentrations differed between males and
      females, nor did they increase with age in male samples. MO-CB and DO-CB
      concentrations increased with age in males, but not in females, and
      concentrations of total MO-CB and DO-CB were usually lower in females than in
      males. Changes in the distribution of PCB congeners between the 1980s and the
      1990s are consistent with atmospheric transport processes becoming increasingly
      important in the introduction of PCBs to the Arctic in recent years.

PMID- 16278009
TI  - Polymorphisms in the promoter regions of the matrix metalloproteinases-1, -3, -7,
      and -9 and the risk of epithelial ovarian cancer in China.
AB  - PURPOSE: To investigate the association of single nucleotide polymorphisms (SNP)
      in the promoter region of the matrix metalloproteinases-1 -1607bp1G/2G, matrix
      metalloproteinases-3 -1171bp5A/6A, matrix metalloproteinases-7 A-181G and matrix
      metalloproteinases-9 C-1562T with susceptibility to ovarian cancer in a
      population of North China. EXPERIMENTAL DESIGN: We analyzed four different
      functional promoter polymorphisms in the respective genes by polymerase chain
      reaction (PCR)-restriction fragment length polymorphism (RFLP) in a sample of
      patients with epithelium ovarian cancer and control women, all from North China.
      RESULTS: No significant difference was detected between the patient and control
      groups in genotype and allelotype distribution of MMP-1, MMP-3, MMP-9 of the
      polymorphisms studied. However, the genotype and allelotype of the MMP-7
      distribution in ovarian cancer patients were significantly different from that in
      healthy controls. The frequency of the -181G allele of MMP-7 in patients was
      significantly higher than that in healthy controls women (8.2% vs. 2.8%, P =
      0.002). Compared to the A/A genotype, the genotypes with the -181G allele (A/G +
      G/G) significantly increased susceptibility to ovarian cancer, with adjusted odds
      ratio [OR] = 3.53 95% confidence interval [CI] [1.58 to 7.89]. CONCLUSIONS: The
      study suggested that a possible association between the MMP-7 A/G polymorphism
      with susceptibility to epithelium ovarian cancer, but there is no support for an
      association of the selected MMP-1 1G/2G, MMP-3 5A/6A, and MMP-9 C/T polymorphisms
      with the risk for ovarian cancer.

PMID- 16278010
TI  - Comparison of secondary and primary ovarian malignancies reveals differences in
      their pre- and perioperative characteristics.
AB  - OBJECTIVE: Preoperative differentiation of primary and metastatic ovarian tumors
      is difficult. Young age of the patient, bilateralism and reduced multilocularity
      are cited characteristics of secondary ovarian malignancies. We sought to
      identity pre- and perioperative factors which may aid in differentiating
      metastatic ovarian tumors from primary ovarian malignancies. PATIENTS AND
      METHODS: We performed a retrospective analysis of demographic parameters,
      preoperative serum tumor marker levels and ultrasonographic as well as operative
      findings in 38 patients with secondary ovarian malignancies and 76 control
      patients with primary epithelial ovarian cancer. All patients were treated at our
      institute from 1996 to 2003. RESULTS: The proportion of secondary ovarian tumors,
      of all ovarian malignancies, was 5.2%. The most common sites of origin were the
      gastrointestinal tract (42%), breast (29%) and peritoneum (16%). Fifty-eight
      percent of the patients with a secondary ovarian tumor had a history of previous
      malignancy; 42% of the primary malignancies were detected only following
      diagnosis of ovarian metastasis. The two patient groups (primary or secondary
      ovarian malignancy) could not be distinguished by age, parity, menopausal status
      or history of hysterectomy. Of the serum markers, the preoperative level of serum
      CA 125 was not different between the two groups. Both serum tumor-associated
      trypsin inhibitor (TATI) (7.2 +/- 9.6 vs. 4.7 +/- 9.4 mug/l [mean +/- SD]) and
      carsinoembryonic antigen (CEA) levels (19.7 +/- 30.8 vs. 6.7 +/- 120.0 mug/l)
      were higher in the group with secondary malignancies (P < 0.02). The metastatic
      ovarian tumors, as measured preoperatively by ultrasonography (US), were smaller
      (64 mm, 62-89 mm [median, 95% Cl]) than the primary tumors (105 mm, 104-134 mm)
      (P < 0.0005). The same was true for tumor sizes measured at surgery (P < 0.05).
      Furthermore, the secondary tumors were more often solid (50 vs. 10%) (P < 0.005),
      and more seldom cystic-solid (17 vs. 55%) (P < 0.001). Presence of ascites was
      more common among patients with primary ovarian malignancies in both preoperative
      US (P < 0.01) and at operation (P < 0.0001). Bilateralism, presence of adhesions,
      and carcinosis did not differ between the two groups. CONCLUSIONS: When
      evaluating a patient with an ovarian tumor, a history of malignancy strongly
      suggests a metastatic nature. Size less than 9 cm, solid structure, absence of
      ascites and elevated serum CEA and TATI levels were typical features associated
      with secondary ovarian malignancies.

PMID- 16278011
TI  - Anxiolytic and antidepressant-like effects of the hydroalcoholic extract from
      Aloysia polystachya in rats.
AB  - Behavioral effects of a hydroalcoholic extract from leaves of Aloysia polystachya
      (Griseb.) Moldenke (Verbenaceae) were studied in female Sprague-Dawley rats. The
      extract was administered intraperitoneally and its effects on spontaneous motor
      activity (total motility, locomotion, rearing and grooming behavior) were
      monitored. Anxiolytic-like properties were studied in the elevated plus-maze
      (EPM) test and the possible antidepressant-like actions were evaluated in the
      forced swimming test (FST). The results revealed that high doses of the extract
      (25 and 50 mg/kg, i.p.) caused a significant decrease in total motility,
      locomotion, rearing and grooming behavior. All doses injected (from 1.56 to 50
      mg/kg) increased the exploration of the EPM open arms in a similar way to that of
      diazepam (1 mg/kg, i.p.). In the FST, the extract (12.5, 25 and 50 mg/kg) was as
      effective as fluoxetine (10 mg/kg, i.p.) and imipramine (12.5 mg/kg, i.p.) in
      reducing immobility, along with a significant increase in swimming and climbing,
      respectively. These results suggest that some of the components of the
      hydroalcoholic extract of A. polystachya, such as thujone and carvone among
      others, may have sedative, anxiolytic and antidepressant-like properties which
      deserve further investigation.

PMID- 16278012
TI  - Manipulation and control of the estrous cycle in pasture-based dairy cows.
AB  - Treatments designed to synchronize luteolysis, preovulatory follicular
      development, and ovulation, and resynchronize estrus after a first AI have
      improved responses to synchronization treatments. Protocols based only on the use
      of PGF result in variable onset of estrus. Concentrations of progesterone prior
      to administering PGF have affected submission rates and fertility while
      administration of estradiol benzoate (EB) after inducing luteolysis has improved
      the synchrony of estrus and ovulation in some studies. In pasture-based dairy
      cows, GnRH-based protocols have generally resulted in one-third of both anestrous
      and cycling cows conceiving following synchronization of ovulation and timed AI.
      Protocols which use intravaginal progesterone releasing inserts (IVP4) are
      effective in inducing estrus in over 90% of treated dairy cows. Resynchronization
      of estrus after reinsertion of an IVP4 also improves the synchrony of returns to
      estrus, but pregnancy rates to the first AI have been reduced in some studies,
      and submission rates at a resynchronized estrus are less than at the first
      synchronized estrus. Administration of EB can be used to synchronize follicle
      wave emergence in resynchronized cows with intervals to new wave emergence
      comparable to that in cows synchronized for a first AI, but plasma concentrations
      of progesterone following treatment may be reduced. Synchronization of estrus and
      ovulation can be enhanced by administration of EB or GnRH during proestrus, but
      dose, timing and stage of follicular development at the time of treatment can
      affect outcomes.

PMID- 16278013
TI  - The prevalence of self-reported health problems and haemoglobin status of
      Sudanese adolescents.
AB  - In this paper we describe self-reported health problems and haemoglobin status
      among 1200 Sudanese adolescents (53.2% females, 46.8% males). Many adolescents
      report their general health as excellent and good (84%). A large number, however,
      report separate physical and psychological complaints. Report of psychological
      complaints is equal for both gender, and more psychological problems are reported
      with increasing age. Females and age groups 13-15 more often report chronic
      diseases. Malaria consistently has a relatively high prevalence. The overall
      prevalence of anaemia in our study is 32% (46.9% males, 19.2% females). The
      findings in our study do not sustain the traditional assumption that adolescence
      is a healthy period in human life. Implications for Sudanese health policies are
      discussed.

PMID- 16278014
TI  - Tissue engineering-based cartilage repair with allogenous chondrocytes and
      gelatin-chondroitin-hyaluronan tri-copolymer scaffold: a porcine model assessed
      at 18, 24, and 36 weeks.
AB  - We previously showed that cartilage tissue can be engineered in vitro with
      porcine chondrocytes and gelatin/chondoitin-6-sulfate/hyaluronan tri-copolymer
      which mimic natural cartilage matrix for use as a scaffold. In this animal study,
      15 miniature pigs were used in a randomized control study to compare tissue
      engineering with allogenous chondrocytes, autogenous osteochondral (OC)
      transplantation, and spontaneous repair for OC articular defects. In another
      study, 6 pigs were used as external controls in which full thickness (FT) and OC
      defects were either allowed to heal spontaneously or were filled with scaffold
      alone. After exclusion of cases with infection and secondary arthritis, the best
      results were obtained with autogenous OC transplantation, except that integration
      into host cartilage was poor. The results for the tissue engineering-treated
      group were satisfactory, the repair tissue being hyaline cartilage and/or
      fibrocartilage. Spontaneous healing and filling with scaffold alone did not
      result in good repair. With OC defects, the subchondral bone plate was not
      restored by cartilage tissue engineering. These results show that tri-copolymer
      can be used in in vivo cartilage tissue engineering for the treatment of FT
      articular defects.

PMID- 16278015
TI  - Epitope tagging for tracking elastin-like polypeptides.
AB  - Elastin-like polypeptides (ELPs) are a class of biocompatible, non-immunogenic
      and crosslinkable biomaterials that offer promise for use as an injectable
      scaffold for cartilage repair. In this study, an oligohistidine (His(6)) epitope
      tag was incorporated at the N-terminus of an ELP using recombinant DNA techniques
      to permit tracking without compromising on material biocompatibility. His(6)
      tagged ELPs were successfully detected by Western blot analysis and quantified by
      ELISAs following digestion with trypsin. The mass of His(6) tagged ELP fragments
      freed from a crosslinked ELP hydrogel after digestion with trypsin correlated
      highly with hydrogel weight loss, providing evidence of the tag's capability to
      enable tracking of enzymatic degradation of the ELP hydrogel. The His(6) tag also
      facilitated recognition of crosslinked ELPs from background staining of articular
      cartilage. These results suggest that the His(6) epitope tag has the potential to
      track ELP scaffold loss independently of newly formed tissue mass for evaluating
      matrix remodeling in vivo.

PMID- 16278016
TI  - Schizophrenia and violent crime: the experience of parents.
AB  - Individuals with schizophrenia have an increased risk of committing a violent
      crime, although their contribution to the overall criminality in society is
      small. In this qualitative study we have interviewed parents of adult sons,
      diagnosed with schizophrenia and who recently had been referred to forensic
      psychiatric treatment due to a violent crime, with an aim to explore the parents'
      experiences and emotional reactions. Four events, or status passages, emerged as
      crucial and common for all parents. These were the onset of the mental disorder,
      the diagnosis of schizophrenia, the violent behaviour/criminality and the recent
      referral to forensic psychiatric treatment. Every passage evoked strong emotional
      reactions such as guilt, fear, disappointment, anger and relief, which in return
      led to different actions taken. Unawareness of the character and severity of
      their sons' mental illness and the type of violent criminality they had committed
      were common and complicated contacts both between the parents and their sons, and
      also between family members and official authorities. The findings emphasize that
      psychiatric health care professionals must take the initiative and responsibility
      for information, education and support of family members.

PMID- 16278017
TI  - Lipodystrophy and serum lipid abnormalities in HIV-positive sub-Saharan
      population on ART.
AB  - To evaluate whether racial factors may be involved in the development of ART
      induced lipodystrophy and/or lipid serum abnormalities, we carried-out a case
      control study on all 23 consecutive anti-HIV-positive sub-Saharan black African
      patients observed from September 20fc01 to December 2001 ('Cases') and 23
      Caucasian 'Controls' pair-matched for sex, age (+/-5 years), number of CD4 cells
      (+/-100 cells), clinical stage of HIV infection, overall duration (+/-3 months)
      of anti-retroviral treatment and type and duration (+/-3 months) of the last anti
      retroviral regimen. The cases, as compared with the controls, less frequently
      showed lipodystrophy (4.4 vs. 65.2%, P<0.001) and hypertriglyceridemia (8.8 vs.
      56.5%, P<0.005), whereas the prevalence of subjects with hypercholesterolemia was
      similar in the two groups (30 and 39.1%, respectively). Overall, the prevalence
      of patients lacking both lipodystrophy and serum lipid abnormalities was markedly
      higher for the cases than for the controls (69.5 vs. 13%, P<0.001). This study
      seems to indicate that anti-retroviral-induced lipodystrophy and
      hypertriglyceridemia may be associated to some racial factor.

PMID- 16278018
TI  - Fournier's gangrene treated by simultaneously using colostomy and open drainage.
AB  - We report our findings and results on treating a patient with Fournier's gangrene
      by using colostomy along with open drainage. A 39-year-old male had noticed a
      swelling and experienced pain in the scrotal sac approximately 1 week before his
      admission. On admission, his symptoms aggravated and he experienced constipation
      and difficulty in urination. Local examination of the scrotum circumference
      revealed a remarkable swelling, and redness and sloughing that had extended to
      the perianal area. In an emergency operation, incision and drainage of the
      scrotum, double-barrelled colostomy at the transverse colon, and reconstruction
      of the percutaneous cystotomy were performed. Postoperative open wound was
      cleaned twice a day and intravenous infusions of 1g imipenem/cilastatin sodium
      and 1.2g clindamycin phosphate were administered daily. The patient was
      discharged 61 days after the operation. Fournier's gangrene has a high mortality
      rate, and in severe cases that are complicated with infection protracted from
      defecation, dyschezia and difficulty in urination, we believe that it would be
      most effective to perform an open drainage and a colostomy simultaneously.

PMID- 16278019
TI  - Dopamine-glutamate reciprocal modulation of release and motor responses in the
      rat caudate-putamen and nucleus accumbens of "intact" animals.
AB  - Functional interactions between dopaminergic neurotransmission and glutamatergic
      neurotransmission are well known to play a crucial integrative role in the
      striatum, the major input structure of the basal ganglia now widely recognized to
      contribute to the control of motor activity and movements but also to the
      processing of cognitive and limbic functions. However, the nature of these
      interactions is still a matter of debate and controversy. This review (1)
      summarizes anatomical data on the distribution of dopaminergic and glutamatergic
      receptors in the striatum-accumbens complex, (2) focuses on the dopamine
      glutamate interactions in the modulation of each other's release in the striatum
      accumbens complex, and (3) examines the dopamine-glutamate interactions in the
      entire striatum involved in the control of locomotor activity. The effects of
      dopaminergic and glutamatergic receptor selective agonists and antagonists on
      dopamine and glutamate release as well on motor responses are analyzed in the
      entire striatum, by reviewing both in vitro and in vivo data. Regarding in vivo
      data, only findings from focal injections studies in the nucleus accumbens or the
      caudate-putamen of "intact" animals are reviewed. Altogether, the available data
      demonstrate that dopamine and glutamate do not uniformly interact to modulate
      each others' release and postsynaptic modulation of striatal output neurons.
      Depending on the receptor subtypes involved, interactions between dopaminergic
      and glutamatergic transmission vary as a multiple and complex combination of
      tonic, phasic, facilitatory, and inhibitory properties.

PMID- 16278020
TI  - Stress-induced elevation of glucocorticoids increases microglia proliferation
      through NMDA receptor activation.
AB  - The immunosuppressive nature of glucocorticoids has been well documented both in
      vitro and in vivo. This glucocorticoid-mediated immunosuppression has also been
      observed in immune cells within the central nervous system (CNS). For example,
      microglia have previously been shown to exhibit decreased proliferation, cytokine
      production, and antigen presentation upon treatment with glucocorticoids in
      vitro. Despite these in vitro findings, the impact of glucocorticoids on
      microglia function in vivo has not been fully investigated. To determine the
      interaction between glucocorticoids and microglia within the CNS, we used a
      restraint model of psychological stress to elevate corticosterone levels in mice.
      Quantification of microglia from stressed mice indicated that four sessions of
      stress induced the proliferation of microglia. This proliferation was a function
      of corticosterone-induced activation of the N-methyl-D-aspartate (NMDA) receptor
      within the CNS since blockade of corticosterone synthesis, the glucocorticoid
      receptor, or the NMDA receptor each prevented stress-induced increases in
      microglia number. In addition, the NMDA receptor antagonist MK-801 prevented
      increases in microglia following exogenous corticosterone administration to non
      stressed mice. We conclude that activation of the NMDA receptor and subsequent
      microglia proliferation is a downstream effect of elevated corticosterone levels.
      These findings demonstrate that elevated levels of glucocorticoids are able to
      activate microglia in vivo and suggest that stress is able to induce a pro
      inflammatory response within the CNS. A pro-inflammatory microglia response may
      be a contributing factor in the development of various stress-induced
      inflammatory conditions in the CNS.

PMID- 16278021
TI  - Central nervous system findings by magnetic resonance in children with profound
      sensorineural hearing loss.
AB  - INTRODUCTION: High-resolution magnetic resonance studies are an important tool in
      the investigation of the etiology of childhood sensorineural hearing loss. An
      added benefit with magnetic resonance is the ability to screen the central
      nervous system for findings which may adversely affect the neurodevelopmental
      outcome of these children. OBJECTIVE: To determine the proportion of cases and
      significance of associated intracranial abnormalities as detected by central
      nervous system high-resolution magnetic resonance imaging in children with
      profound sensorineural hearing loss. METHODS: Retrospective chart review of
      children undergoing evaluation for cochlear implantation in a tertiary care
      academic children's hospital with high-resolution magnetic resonance of the
      temporal bone and brain during a 21 month period. Magnetic resonance studies were
      interpreted by an experienced senior neuroradiologist blinded to the identity and
      clinical data of the patients. RESULTS: Forty patients were identified. All had
      the same magnetic resonance study consisting of a 3D high-resolution sequence
      through the temporal bone as well as a T1 sagittal and T2 axial screening
      sequence of the brain. Eight patients (20%) showed significant brain
      abnormalities by magnetic resonance imaging ranging from myelination delays to
      migrational anomalies. Temporal bone abnormalities were not seen. Three patients
      with Connexin-26 mutations had no associated brain abnormalities by magnetic
      resonance. CONCLUSIONS: A significant proportion of our patients being
      investigated by magnetic resonance imaging for profound sensorineural hearing
      loss show migrational abnormalities of the central nervous system, suggesting a
      central origin to their hearing loss. Some of these findings may result in
      neurodevelopmental delay and hence, negatively impact the success of cochlear
      implantation. We propose that magnetic resonance imaging of the temporal bone as
      part of the evaluation protocol for cochlear implantation in children should
      include central nervous system screening.

PMID- 16278022
TI  - Apelin protects myocardial injury induced by isoproterenol in rats.
AB  - We aimed to explore the change in level of apelin and its receptor APJ during
      myocardial injury and the therapeutic effects of apelin in myocardial injury. Rat
      myocardial injury was induced by subcutaneous injection of a high dose of
      isoproterenol (ISO); apelin and APJ mRNA levels were determined by RT-PCR; APJ
      protein was determined by Western blot; EIA and RIA were used to measure the
      apelin content and receptor binding, respectively. Plasma lactate dehydrogenase
      (LDH) activity and myocardial and plasma malondialdehyde (MDA) contents were
      higher in ISO-treated hearts than that in controls. ISO-treated rats showed lower
      +/-LV dp/dt(max) values and higher LVEDP value (all P<0.01), which suggested
      severe heart failure. As well, the apelin content in plasma, atrial and
      ventricular myocardium was decreased by 27%, 30% and 25% (P<0.01), respectively.
      The mRNA levels of apelin and APJ in myocardia were also markedly reduced; but
      the APJ protein level in myocardia was increased. However, administration of
      apelin significantly ameliorated myocardial injury and ISO-induced heart failure.
      Compared with the ISO-alone group, the group given low-dosage apelin (5
      nmol/kg/day) had 39% and 66% higher +LV dp/dt(max) and -LV dp/dt(max) values, and
      40.7% lower LVEDP value (P<0.01), and the leakage of myocardial LDH and increased
      MDA content were attenuated (all P<0.01). Interestingly, bolus injections of
      apelin (10 nmol/kg/day) resulted in potent inotropic effects in ISO-treated rats.
      ISO-induced myocardial injury resulted in hypoexpression of apelin and its
      receptor APJ, and the administration of exogenous apelin ameliorated heart
      failure and myocardial injury. Apelin could have a cardioprotective effect, and
      the apelin-APJ system may be a new therapeutic target in myocardial injury and
      heart failure.

PMID- 16278023
TI  - Recurrent noisy pneumothorax mimicking pericarditis.
AB  - Sounds related to the cardiac cycle may have an extra-cardiac origin. We report a
      case of recurrent noisy pneumothorax producing a loud rub, audible at a distance
      from the patient and initially diagnosed as pericarditis. The sounds and their
      mechanisms of production in this condition are also discussed.

PMID- 16278024
TI  - Like mother like son.
AB  - A 68-year-old female with history of anterior wall myocardial infarction (MI) 20
      years earlier, underwent coronary angiography after having a non ST elevation MI.
      Before the procedure, the patient and her close family, including her husband and
      2 sons were given thorough explanation of the procedure, its risks and benefits.
      A totally occluded mid LAD with collaterals from the RCA was found. Besides this
      presumably 20-year-old chronic total occlusion of the LAD, no other significant
      lesions were detected, hence medical therapy was recommended. Twelve hours after
      this diagnostic angiography, the same team was called urgently to perform primary
      PCI on a 41-year-old male, who presented to the emergency department within 4 h
      from onset of chest pain and signs of anterior wall ST elevation MI. The treating
      team immediately recognized the patient as the son of the lady who underwent
      angiography just several hours ago. This time the explanations about the
      procedure were concise. Angiography revealed an acute total occlusion of the mid
      LAD, which was successfully treated. The location of the blockage in mid LAD,
      just distal to the 1st diagonal and a large septal artery, was closely the same
      in the mother and in the son. Genetic predisposition and emotional stress are
      linked together in the present presentation. The proximity of time may be
      attributed to emotional stress while the proximity in location of the culprit
      lesions in these two cases may have genetic factors. To our knowledge, this is
      the first description of an acute MI in a sibling with a coronary artery
      occlusion in the exact anatomy as of the mother, occurring just several hours
      after the mother's coronary angiography.

PMID- 16278025
TI  - Extensive intramural hematoma and coronary artery dissection.

PMID- 16278026
TI  - Rapid detection of fluoroquinolone resistance by isothermal chimeric primer
      initiated amplification of nucleic acids from clinical isolates of Neisseria
      gonorrhoeae.
AB  - To ensure a complete response to fluoroquinolone therapy against Neisseria
      gonorrhoeae infections, rapid susceptibility determinations are required. We
      assessed a new approach, an isothermal chimeric primer-initiated amplification of
      nucleic acids (ICAN)/hybrid-chromatography method to detect rapidly
      fluoroquinolone resistance in N. gonorrhoeae. Comparison of the amplification
      results with fluoroquinolone minimum inhibitory concentrations (MICs), which were
      determined by an agar dilution method, showed that the new method accurately
      determined fluoroquinolone resistance in all ciprofloxacin- and/or gatifloxacin
      resistant isolates, but agreed with results based on MICs in only 6 of 8 (75.0%)
      ciprofloxacin-susceptible and 7 of 12 (58.3%) gatifloxacin-susceptible isolates.
      Our results suggest that this method can rapidly and reliably detect point
      mutations in the gyrA gene as well as fluoroquinolone resistance in resistant
      isolates of N. gonorrhoeae.

PMID- 16278027
TI  - A.O. Re. Hamm, A.I. Weike, 2005. The neuropsychology of fear-learning and fear
      regulation. International Journal of Psychophysiology, 57, 5-14.

PMID- 16278028
TI  - Phenotypic identification and technological properties of lactic acid bacteria
      isolated from traditionally processed fish products of the Eastern Himalayas.
AB  - Sukako maacha, gnuchi, sidra and sukuti are traditional smoked and sun-dried fish
      products of the Eastern Himalayan regions of Nepal and India. A total of 40
      samples of sukako maacha (14), gnuchi (6), sidra (10) and sukuti (10) were
      collected and were analysed for microbial load. Population of lactic acid
      bacteria (LAB) as well as aerobic mesophilic counts ranged from 4.7-8.3 to 5.1
      8.5 log cfu g(-1), respectively. A total of 189 strains of LAB were isolated from
      sukako maacha, gnuchi, sidra and sukuti samples, out of which 171 strains were
      cocci and 15 strains, were heterofermentative lactobacilli. LAB were identified
      on the basis of phenotypic characters including API system as Lactococcus lactis
      subsp. cremoris, Lactococcus lactis subsp. lactis, Lactococcus plantarum,
      Leuconostoc mesenteroides, Enterococcus faecium, Enterococcus faecalis,
      Pediococcus pentosaceus and Weissella confusa. LAB strains produced a wide
      spectrum of enzymes. Some strains of LAB showed antagonistic properties against
      pathogenic strains. None of the strains produced biogenic amines in the method
      applied. This paper is the first report on the microbial composition, mostly
      lactic acid bacteria, of traditionally processed fish products of Eastern
      Himalayas.

PMID- 16278029
TI  - Identification and antagonistic activity of lactic acid bacteria occurring in
      porcine blood from industrial slaughterhouses--a preliminary study.
AB  - Ninety-seven lactic acid bacteria (LAB) were isolated from slaughterhouse porcine
      blood in order to select autochthonous LAB strains for use as biopreservatives of
      this by-product. They were identified by 16S rDNA sequencing; and their
      inhibition capacity was determined against four bacterial species frequently
      found in contaminated blood, i.e. Staphylococcus aureus, Escherichia coli,
      Pseudomonas fluorescens and Bacillus spp. The taxonomic study showed an
      unexpected low diversity of LAB in blood, i.e. only 8 different species were
      found, from which just 4, i.e. Enterococcus raffinosus, Lactobacillus murinus,
      Lactobacillus reuteri and Lactococcus garvieae, amounted to more than 90% of all
      isolates. Inhibition tests in solid culture media proved that S. aureus and
      Bacillus spp. were inhibited by most LAB strains obtained from porcine blood. E.
      coli was the indicator less affected by the isolated LAB species. Several
      isolates efficiently inhibited the growth of all tested indicators.

PMID- 16278030
TI  - Efficient regulation of gene expression using self-contained fiber-modified
      adenovirus vectors containing the tet-off system.
AB  - Previously, we developed single adenovirus (Ad) vectors that contained the gene
      of interest in the E1 deletion region and the transactivator gene for the
      tetracycline-controllable expression system in the E3 deletion region. In the
      present study, we improved the Ad vector-mediated tetracycline-controllable
      expression system by the fiber modification of Ad. We developed fiber-modified Ad
      vectors containing the tet-off system, which are effective in overcoming the
      limitations of conventional Ad vectors, specifically their inefficient gene
      transfer into cells lacking the primary receptor, the coxsackievirus and
      adenovirus receptor (CAR). Ad vectors containing the tet-off system with an Arg
      Gly-Asp (RGD) peptide in the HI loop of the fiber knob or the Ad type 35 fiber
      greatly improved transduction efficiency (more than 1-2-log orders) into the
      cells lacking CAR expression but expressing alphav integrin or CD46,
      respectively. They exhibited vastly higher regulation of gene expression by
      doxycycline. The combination of fiber-modified Ad vectors and the tetracycline
      controllable expression system should offer a powerful tool for gene therapy and
      gene transfer experiment.

PMID- 16278031
TI  - Regiochemical functionalization of a nanoscale cage-like structure: robust core
      shell nanostructures crafted as vessels for selective uptake and release of small
      and large guests.
AB  - As synthetic methods evolve toward the preparation of increasingly complex
      nanostructured materials inspired from biological nano-objects, the ability to
      tailor the three-dimensional architecture and the placement of functional groups
      at well-defined positions within those frameworks is advancing. In this report,
      we demonstrate the ability to functionalize selectively internal and external
      sites (regiochemically) within polymer nanocages, to advance their development as
      synthetic analogs of viral capsids. Nanocages, possessing carbonyl groups on
      their internal surfaces and acrylic acid residues throughout their structure were
      prepared and functionalized, through either Schiff-base chemistry, to attach
      covalently phosphatidylethanolamine-based lipids within the nanocage, or
      carbodiimide-mediated coupling, to attach covalently the lipids throughout the
      shell. The resulting nanostructures were altered by the insertion of molecules
      within and on the structure, including, for the Schiff base functionalized
      nanostructure, an enhanced response to pH and increased uptake of hydrophobic
      guests. Additionally, the use of phosphatidylethanolamine lipids labeled with 7
      nitrobenz-2-oxa-1,3-diazole (NBD) allowed for determination of the environmental
      polarities of the lipid domains within the lipid-nanocage constructs.

PMID- 16278032
TI  - Electrothermally activated microchips for implantable drug delivery and
      biosensing.
AB  - Novel drug delivery and biosensing devices have the potential to increase the
      efficacy of drug therapy by providing physicians and patients the ability to
      precisely control key therapy parameters. Such "intelligent" systems can enable
      control of dose amount and the time, rate, and location of drug delivery. We have
      developed and demonstrated the operation of an electrothermal mechanism to
      precisely control the delivery of drugs and exposure of biosensors. These
      microchip devices contain an array of individually sealed and actuated
      reservoirs, each capped by a thin metal membrane comprised of either gold or
      multiple layers of titanium and platinum. The passage of a threshold level of
      electric current through the membrane causes it to disintegrate, thereby exposing
      the protected contents (drugs or biosensors) of the reservoir to the surrounding
      environment. This paper describes the theory and experimental characterization of
      the electrothermal method and includes in vitro release results for a model
      compound.

PMID- 16278034
TI  - Adult onset type II citrullinemia as a cause of non-alcoholic steatohepatitis.
AB  - Adult onset type II citrullinemia (CTLN2) is an autosomal recessive disease
      accompanied with hyperammonemia and a sudden onset of psychiatric disorders. We
      demonstrated three male patients with CTLN2 having a liver histology of non
      alcoholic steatohepatitis (NASH). Patients with NASH were analyzed for the
      causative gene of CTLN2, SLC25A13 and discussed.

PMID- 16278035
TI  - Vocational analysis of health care professions as a basis for innovative
      curricular planning. An analysis and prognosis of the development of the
      professional competencies of midwives--cornerstones of innovative curricula in
      tertiary education.
AB  - This article describes current and future tendencies in the development of
      curriculum planning for health care professions in Germany, using the example of
      midwifery education. In particular, it discusses 'output-based control' of
      curriculum planning giving consideration to issues related to German education,
      health policies and professional educational theories with a view to the general
      international development. The results of this analysis constitute the starting
      point for the conceptual planning of a dissertation at the medical faculty of the
      Berlin Charite with the goal of developing a competency model for the curriculum
      planning of midwifery education, thus creating a modern curriculum as a basis for
      a fundamental reform of German midwifery education.

PMID- 16278036
TI  - Differences in glycaemic status do not predict weight loss in response to
      hypocaloric diets in obese patients.
AB  - OBJECTIVE: The aim of our study was to detect differences in weigth loss with a
      hypocaloric diet in obese patients depending on their glycaemic status. SUBJECTS
      AND METHODS: A population of 76 obesity outpatients was analysed in a prospective
      way. The following variables were specifically recorded at basal time and after 3
      months of hypocaloric diet (1200 kcal/day): weight, blood pressure, body mass
      index (BMI), waist circumference, and waist-hip ratio. Basal glucose, insulin,
      fibrinogen, cortisol, c-reactive protein, total cholesterol, LDL cholesterol, HDL
      cholesterol and triglycerides blood levels were measured. HOMA was calculated. An
      indirect calorimetry, tetrapolar electrical bioimpedance and a serial assessment
      of nutritional intake with 3 days written food records were performed. RESULTS:
      The mean age was 46.9 +/- 17.1 years and the mean BMI 34.6 +/- 5.3. All subjects
      were weight stable during the 2 weeks period preceding the study (body weight
      change, 0.3 +/- 0.1 kg). Anthropometric measurements showed an average waist
      circumference (108.7 +/- 15.7 cm), waist-to-hip ratio (0.93 +/- 0.11), and
      average weight (88.7 +/- 16.9 kg). Bipolar body electrical bioimpedance showed a
      fat mass of 37 +/- 12.3 kg. Indirect calorimetry showed a resting metabolic rate
      (RMR) (1674.3 +/- 392 kcal/day). Patients were divided in to two groups by
      glycaemic status (group I: normal glycaemic metabolism, fasting glucose levels
      <109 mg/dl; n = 50) and (group II: impaired glycaemic metabolism, fasting glucose
      levels >110 mg/dl, n = 26). Waist circumference (I: 108 +/- 17.1cm vs. 104.6 +/-
      16.7 cm; P < 0.05) and (II: 113.6 +/- 9.8 cm vs. 110.9 +/- 8.9 cm; P < 0.05),
      weight (I: 90.6 +/- 19.2 kg vs. 86.3 +/- 18.6 kg:P < 0.05) and (II: 89.2 +/- 11.3
      kg vs. 86.4 +/- 11.6 kg: P < 0.05) and BMI (I: 34.2 +/- 5.6 vs. 33.7 +/- 5.5; P <
      0.05) and (II: 34.8 +/- 4.2 vs. 34.2 +/- 4.6; P < 0.05) improved in both groups
      with hypocaloric diet. Blood systolic pressure, total cholesterol and LDL
      cholesterol improved in both groups, without statistical differences. In group II
      improved glucose levels and HOMA index, too. Patients of group II had higher
      systolic blood pressure, glucose, total cholesterol, LDL cholesterol,
      triglycerides, lipoprotein (a), RCP levels and HOMA index than patients in group
      I. ANOVA analysis did not show differences among weight loss in tertiles of HOMA
      and glucose. CONCLUSION: Ability to lose weight on a hypocaloric diet over a 3
      month time period does not vary in obese patients as a function of glycaemic
      status. Improvement in cardiovascular risk factors is not related with glycaemic
      status, too.

PMID- 16278037
TI  - Vaccines against typhoid fever.
AB  - Because of high infectivity and significant disease burden, typhoid fever
      constitutes a major global health problem. Implementation of adequate food
      handling practices and establishment of safe water supplies are the cornerstone
      for the development of an effective prevention program. However, vaccination
      against typhoid fever remains an essential tool for the effective management of
      this disease. Currently, there are two well tolerated and effective licensed
      vaccines. One is based on defined subunit virulence (Vi) polysaccharide antigen
      and can be administered either intramuscularly or subcutaneously and the other is
      based on the use of live attenuated bacteria for oral administration. The
      advantages and disadvantages of the various approaches taken in the development
      of a vaccine against typhoid fever are discussed, along with the potential for
      future vaccine candidates.

PMID- 16278038
TI  - Immunological responses after immunisation of mice with microparticles containing
      antigen and single stranded RNA (polyuridylic acid).
AB  - Certain toll-like receptor (TLR) agonists, e.g. CpG DNA, can be used as potent
      vaccine 'adjuvants'. It is known that some sequences of single stranded (ss) RNA
      stimulate proinflammatory and antiviral responses following interaction with TLR
      7 and 8. We have encapsulated ovalbumin (OVA) in the presence and absence of
      polyuridylic acid (poly-U) inside polylactide microparticles. In comparison to
      microparticles containing only OVA, bulk cultures of bone marrow-derived
      plasmacytoid and myeloid dendritic cells produced more (P<0.05) IL-12 and
      interferon (IFN)-alpha when stimulated with microparticles containing OVA and
      poly-U. Subcutaneous injection of comicroencapsulated OVA and poly-U resulted in
      statistically elevated levels of serum anti-OVA IgG1 (P<0.05 versus naive mice).
      Conversely, anti-OVA IgG1 levels in C57 BL6 mice immunised with OVA loaded
      microparticles (without RNA) were statistically indifferent to naive animals.
      Furthermore, injection of coencapsulated OVA and poly-U resulted in (P<0.05)
      greater numbers of OVA specific IFN-gamma secreting T-cells as compared with mice
      injected with OVA loaded microparticles. A similar trend was seen in mice
      immunised with OVA loaded microparticles decorated with CpG or solutions of
      admixed OVA and CpG (P<0.05). These data demonstrate, for the first time, that
      appropriately formulated ssRNA can act as a potent adjuvant and modulator of
      adaptive immunological responses.

PMID- 16278039
TI  - Characterization of trace organic contaminants in marine sediment from Yeongil
      Bay, Korea: 1. Instrumental analyses.
AB  - Concentrations of polychlorinated biphenyls (PCBs), organochlorine (OC)
      pesticides (HCB, HCHs, CHLs, and DDTs), polycyclic aromatic hydrocarbons (PAHs),
      alkylphenols (APs), and bisphenol A (BPA) were measured in 26 marine sediments
      collected from Yeongil Bay, Korea, in order to characterize their spatial
      distribution and sources. PCBs (2.85-26.5 ng/g, dry wt.) were detected mainly in
      the inner bay locations Mean OC pesticide ranged from 1.16 ng/g dry wt. for HCH
      to 0.05 ng/g dry wt. for HCB). PAH concentrations ranged from <10.0 to 1870
      (mean: 309)ng/g dry wt., and were predominated 3- and 4-ring congeners.
      Concentrations of APs, such as nonylphenol, octylphenol, butylphenol (means 89.1,
      4.61, 11.0 ng/g dry wt., respectively), were greater at locations proximal to
      municipal wastewater discharges. Concentrations of PCBs and PAHs were great near
      shipyards and industrial complexes. Vertical profiles of PAHs and APs indicated
      that they have been associated with sediments since the 1950s.

PMID- 16278040
TI  - Comparison of the role of the sea club-rush Scirpus maritimus and the sea rush
      Juncus maritimus in terms of concentration, speciation and bioaccumulation of
      metals in the estuarine sediment.
AB  - The capability of Scirpus maritimus and of Juncus maritimus to accumulate metals
      and the role of each plant on the physico-chemical composition of sediments, from
      Douro river estuary (NW Portugal), were investigated through a year of plants'
      life. The contents of Al, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn were determined (by
      atomic absorption spectrophotometry) in sediment, rhizosediments (those in
      contact with each plant roots and rhizomes) and different tissues of S. maritimus
      and of J. maritimus. Both plants influenced the sediment composition
      (concentrating metals around its roots) and were able to bioaccumulate Cd, in
      spite of some seasonal variations in the metal levels in the system (both in
      rhizosediments and plants' roots). Therefore, both plants showed to have
      potential for Cd phytostabilization. S. maritimus could also concentrate Pb in
      its roots, probably by sorption on the root surface in (hydr)oxide forms,
      therefore, denoting capability for Pb phytostabilization.

PMID- 16278041
TI  - Fate of heavy metals after application of sewage sludge and wood-ash mixtures to
      short-rotation willow coppice.
AB  - Short-rotation willow coppice (SRWC), grown on farmland in Sweden for energy
      biomass production, was fertilised with sewage sludge and wood-ash mixtures on
      the basis of the permitted annual phosphorus supply. Two identical experiments
      were conducted in central Sweden, on two newly harvested commercial SRWC fields.
      The maximum legally permitted amount of the sludge-ash mixture, sludge only, ash
      only, and twice the maximum permitted sludge-ash amount, were applied. The aim
      was to assess the effect of pH changes following treatment, on the ability of
      SRWC to take up large amounts of Cd and other metals. The remediation effect of
      SRWC was also studied. Under the experimental conditions applied, uptake by SRWC
      was unaffected by pH changes. The differences between the amounts of metals
      experimentally applied, less the uptake by SRWC after a potential harvest, were
      broadly within the permitted limits. For Cd, a reduction of total amounts in soil
      was observed.

PMID- 16278042
TI  - Diamine oxidase, a plasma biomarker in rats to GI tract toxicity of oral
      fluorouracil anti-cancer drugs.
AB  - Diamine oxidase (DAO; EC 1.4.3.6), which catabolizes a variety of substrates
      including histamine and diamines, is the degradative enzyme of the catabolic
      pathway of polyamines found in high activity in the mature upper villus cells of
      the rat intestinal mucosa [Luk, G.D., Bayless, T.M., Baylin, S.B., 1983. Plasma
      post-heparin diamine oxidase. Sensitive provocative test for quantitating length
      of acute intestinal mucosal injury in the rat. J. Clin. Invest. 71, 1308-1315;
      Wolvekamp, M.C.J., de Bruin, R.W.F., 1994. Diamine oxidase: an overview of
      historical, biochemical and functional aspects. Dig. Dis. 12, 2-14]. Rats were
      given 1-week repeated oral administration of anti-cancer drugs S-1, containing
      FT+CDHP+Oxo, and FCD, containing FT+CDHP, and the ameliorating effect of Oxo on
      the rat gastrointestinal (GI) tract toxicity from 5-FU was evaluated by measuring
      plasma DAO activity which is related to the enzyme located in the rat intestinal
      mucosa. Plasma DAO activity in the FCD-treated group was significantly less than
      that in the S-1-treated group while the jejunal mucosal area in the FCD group was
      significantly smaller than that in the S-1 group. In addition the
      histopathological findings in the FCD group showed villus atrophy in the jejunal
      mucosa which was not observed in the S-1 group. The degree of these findings
      correlated with the plasma DAO levels. Therefore, the protective effect of Oxo on
      5-FU-induced GI tract toxicity was clarified by measuring plasma DAO activity in
      rats. In summary, DAO is a very sensitive plasma biomarker and will be useful for
      the quantitative evaluation of the small intestinal mucosal lesions induced by
      the anti-cancer drug, 5-FU, in rats.

PMID- 16278043
TI  - Topography of EEG complexity in human neonates: effect of the postmenstrual age
      and the sleep state.
AB  - The topography of the EEG of human neonates is studied in terms of its power
      spectral density and its estimated complexity as a function of both the
      postmenstrual age (PMA) and the sleep state. The monopolar EEGs of three groups
      of seven neonates (preterm, term and older term) were recorded during active (AS)
      and quiet sleep (QS) from electrodes Fp1, Fp2, T3, T4, C3, C4, O1 and O2. The
      existence of changes between groups and sleep states in the power of delta,
      theta, alpha and beta bands and in the dimensional complexity of these electrodes
      was tested. Additionally, the nonlinearity of the EEG in each electrode and
      situation was analyzed. The results of the spectral measures show an increment of
      the power in the low frequency bands from AS to QS and with the PMA, which can be
      mainly traced on central and temporal electrodes. This change is shown as well by
      the dimensional complexity, which also presents the greatest differences in the
      central derivations. Moreover, the signals show evidence of nonlinearity in
      almost all the groups and situations, although a dynamic change from nonlinear to
      linear character is apparent in the central electrodes with increased PMA. As a
      result, it is concluded that nonlinear analysis methods provide a clear portrait
      of the integrated brain activity that complements the information of spectral
      analysis in the characterization of the brain development and the sleep states in
      neonates.

PMID- 16278044
TI  - Natriuretic peptides, but not nitric oxide donors, elevate levels of cytosolic
      guanosine 3',5'-cyclic monophosphate in ependymal cells ex vivo.
AB  - Atrial natriuretic peptide-(1-28) (ANP), brain natriuretic peptide-(1-32) (BNP)
      and C-Type natriuretic polypeptide (CNP) occur in the brain, are concentrated in
      the anteroventral area of the third cerebral ventricle and participate in the
      regulation of body fluid homeostasis. The ventricles of the mammalian brain are
      lined by a continuous monolayered epithelium of polyciliated ependymal cells. In
      the adult rat, the ependymocytes continue to express the intermediate filament
      vimentin, but do not contain glial fibrillary acidic protein. Ependymal functions
      are poorly understood, but may extend to osmoregulation and volume sensing.
      Ependymal cells possess receptors for the natriuretic peptides, and in cell
      culture respond to them with an increase in their cyclic GMP content. In this
      study, a cyclic GMP-specific antibody was employed together with an ex vivo brain
      slice system to assess the ependymal response to ANP, BNP and CNP under close to
      life-like conditions. While ANP in concentrations of 0.1 nM and 1 nM had no
      effect, at concentrations of 10nM and 100 nM it increased ependymal cyclic GMP
      levels in a concentration-dependent manner. The other natriuretic peptides BNP,
      and CNP, also increased the cyclic GMP content of ependymocytes, while nitric
      oxide (NO) donors had no effect. However, in contrast to the natriuretic
      peptides, the NO donors elevated the level of cyclic GMP in the brain parenchyma
      below the ependymal layer.

PMID- 16278045
TI  - Chemokine receptor CCR5 expression in in vitro differentiating human fetal neural
      stem/progenitor and glioblastoma cells.
AB  - We have studied the expression of CC-chemokine receptor 5 (CCR5) at the protein
      level in human fetal neural stem/progenitor and glioblastoma cells in
      differentiation, using immunocytochemistry, routine fluorescence microscopy and
      confocal laser microscopy analysis. Neural stem/progenitor cells were isolated
      from the brain of 18-21 weeks old fetuses aborted due to medical indications, and
      propagated in vitro as neurospheres. Glioblastoma cells were isolated from tumour
      biopsies and propagated in vitro as spheres according to the same methods as
      fetal neural cells. Two stem/progenitor cell neurosphere and two glioblastoma
      spheroid cultures were initiated to differentiate using RA and cAMP. The cells
      were fixed and analyzed immunocytochemically on the 1st, 3rd, and 8th days of the
      differentiation. The expression of CCR5 was localized mainly in the cell nuclei,
      and was usually much weaker, if at all, in cytoplasm. Confocal laser microscopy
      analysis confirmed the same location. The expression of CCR5 was the highest one
      on the 3rd day of differentiation in all cultures, but showed also distinct
      differences between cultures, and in normal fetal differentiated stem/progenitor
      cells the expression of CCR5 was much weaker than in differentiated glioblastoma
      spheric cells.

PMID- 16278047
TI  - Characterization of FBX25, encoding a novel brain-expressed F-box protein.
AB  - F-box proteins (FBPs) confer substrate specificity to the SCF-type
      (Skp1/Cul1/FBP) of ubiquitin ligase complexes through their F-box. Multiple FBPs
      have been predicted, but experimental evidence is lagging. We report on the
      predicted human FBP hFBX25 which we found to be disrupted in a mentally retarded
      translocation carrier suffering from epileptic seizures. We investigated hFBX25's
      genomic organization and established hFBX25 as an FBP by verifying its
      interaction with Skp1 and Cul1. In the process, we identified an atypical serine
      residue in the F-box which is crucial for the hFBX25-Skp1 binding. We determined
      hFBX25's subcellular localization. We found strong transcription in human brain.
      In mouse embryonic sections, mFbx25 shows predominantly neuronal expression and
      in adult mouse brain, expression is confined to the hippocampus, the cerebral
      cortex and the Purkinje cell layer. Interestingly, aberrations in the ubiquitin
      pathway have been linked to neurological conditions.

PMID- 16278046
TI  - Solubilization, purification and reconstitution of Ca(2+)-ATPase from bovine
      pulmonary artery smooth muscle microsomes by different detergents: preservation
      of native structure and function of the enzyme by DHPC.
AB  - The properties of Ca(2+)-ATPase purified and reconstituted from bovine pulmonary
      artery smooth muscle microsomes {enriched with endoplasmic reticulum (ER)} were
      studied using the detergents 1,2-diheptanoyl-sn-phosphatidylcholine (DHPC),
      poly(oxy-ethylene)8-lauryl ether (C(12)E(8)) and Triton X-100 as the solubilizing
      agents. Solubilization with DHPC consistently gave higher yields of purified
      Ca(2+)-ATPase with a greater specific activity than solubilization with C(12)E(8)
      or Triton X-100. DHPC was determined to be superior to C(12)E(8); while that the
      C(12)E(8) was determined to be better than Triton X-100 in active enzyme yields
      and specific activity. DHPC solubilized and purified Ca(2+)-ATPase retained the
      E1Ca-E1*Ca conformational transition as that observed for native microsomes;
      whereas the C(12)E(8) and Triton X-100 solubilized preparations did not fully
      retain this transition. The coupling of Ca(2+) transported to ATP hydrolyzed in
      the DHPC purified enzyme reconstituted in liposomes was similar to that of the
      native micosomes, whereas that the coupling was much lower for the C(12)E(8) and
      Triton X-100 purified enzyme reconstituted in liposomes. The specific activity of
      Ca(2+)-ATPase reconstituted into dioleoyl-phosphatidylcholine (DOPC) vesicles
      with DHPC was 2.5-fold and 3-fold greater than that achieved with C(12)E(8) and
      Triton X-100, respectively. Addition of the protonophore, FCCP caused a marked
      increase in Ca(2+) uptake in the reconstituted proteoliposomes compared with the
      untreated liposomes. Circular dichroism analysis of the three detergents
      solubilized and purified enzyme preparations showed that the increased negative
      ellipticity at 223 nm is well correlated with decreased specific activity. It,
      therefore, appears that the DHPC purified Ca(2+)-ATPase retained more organized
      and native secondary conformation compared to C(12)E(8) and Triton X-100
      solubilized and purified preparations. The size distribution of the reconstituted
      liposomes measured by quasi-elastic light scattering indicated that DHPC
      preparation has nearly similar size to that of the native microsomal vesicles
      whereas C(12)E(8) and Triton X-100 preparations have to some extent smaller size.
      These studies suggest that the Ca(2+)-ATPase solubilized, purified and
      reconstituted with DHPC is superior to that obtained with C(12)E(8) and Triton X
      100 in many ways, which is suitable for detailed studies on the mechanism of ion
      transport and the role of protein-lipid interactions in the function of the
      membrane-bound enzyme.

PMID- 16278048
TI  - Saving the zone of stasis: is glutathione effective?
AB  - One of the main subjects that burn researches are focused on is saving the zone
      of stasis. There are many molecules that are used for this purpose, but all have
      their drawbacks. Glutathione is one of the major buffer molecules of the cells
      and is known to increase the thermo-resistance of the cells. In this study, the
      effect of the systemic glutathione on the zone of stasis was evaluated. The
      results showed that glutathione is an effective molecule for saving the zone of
      stasis. It is well-known cheap, and easy to use.

PMID- 16278049
TI  - Red blood cell and tissue water content in experimental thermal injury.
AB  - Oedema formation and changes in local blood flow are known phenomena in burns.
      The relationship between these two is not clearly described. The aim of this
      study was firstly to examine both the contents of red blood cells and tissue
      water in skin and subcutaneous fat after experimental burns of different depths
      in pigs, and secondly, to confirm our recent findings of the increased dielectric
      constant of skin and subcutaneous fat reflecting considerable oedema formation,
      especially in fat after thermal injury. METHODS: Superficial, partial and full
      thickness contact burns were created to pigs and followed for 24h. Radioactive Cr
      51 labelling of red cells was used to estimate the number of red cells in tissue,
      and the absolute amount of water was determined by lyophilization. RESULTS: A
      decreased number of labelled red cells in skin and an increase in tissue water in
      subcutaneous fat were found regardless of burn depth. The highest water amount in
      fat was found in the partial thickness burns. CONCLUSION: All burn depths
      resulted in a diminished number of labelled red blood cells in skin and a
      significant increase in the absolute water amount in subcutaneous fat at 24h post
      injury. The findings in fat support our recent findings of highly elevated
      dielectric constants measured by the new in vivo method of dielectric
      measurements.

PMID- 16278050
TI  - Antibiotic not linked to autism.

PMID- 16278051
TI  - 5-Lipoxygenase (ALOX5) and FLAP (ALOX5AP) gene polymorphisms as factors in
      vascular pathology and Alzheimer's disease.
AB  - We first hypothesized in 2000 that a polymorphism of the human gene encoding the
      enzyme 5-lipoxygenase (5-LOX) might be associated with Alzheimer's disease. Only
      a little progress has been made in directly testing our proposal. However,
      additional important new data lead us to hypothesize that genetic variability not
      only in the 5-LOX gene, i.e., ALOX5, but also in polymorphism of the five
      lipoxygenase activating protein (FLAP) gene, i.e., ALOX5AP, may be associated
      with Alzheimer's pathology. Studies in mice followed by several extensive
      clinical studies have identified ALOX5 and ALOX5AP polymorphisms as strong risk
      factors for atherosclerosis and cerebrovascular pathologies. New data point to a
      significant aggregation of vascular risk factors and risk of Alzheimer's disease.
      Preliminary findings in postmortem brain of Alzheimer's patients identified
      elevated 5-LOX immunostaining in this disease. We suggest that our hypothesis of
      a link between the ALOX5 and ALOX5AP gene polymorphisms and Alzheimer's disease
      could be tested in a clinical setting and in animal models, i.e., transgenic mice
      could be produced by crossing the available 5-LOX-deficient mice with the
      available transgenic mice models of Alzheimer's disease.

PMID- 16278052
TI  - Would blockage of cytokines improve the outcome of pancreatic islet
      transplantation?
AB  - It has been estimated that up to 60% of pancreatic islet tissue undergoes
      apoptosis within the first several days post-transplantation. This strongly
      suggests the involvement of an inflammatory event other than alloantigen-specific
      immune reaction following islet transplantation which contributes to partial
      destruction of grafts. Inflammatory cytokines including IL-1beta, TNF-alpha and
      IFN-gamma are implicated in the pancreatic islet beta-cell death and functional
      loss during autoimmune diabetes and also seem to be involved in early loss of
      islet mass in islet transplantation. Inflammatory cytokines and free oxygen
      radicals released in situ could cause apoptosis and the functional impairment of
      islets after islet transplantation and graft failure. It can be hypothesized that
      preventing destruction of transplanted islets using cytokine blockade could be
      helpful in improving islet transplantation outcome. Several approaches have been
      made based on this hypothesis to examine the effect of inflammatory blockade on
      the islets survival and functional islet mass. Further investigations are
      required to identify most efficient way for block of cytokine-induced damage in
      pancreatic islets transplantation.

PMID- 16278053
TI  - Cold therapy for the reduction of biliary pain.

PMID- 16278054
TI  - Defective induction of senescence during wound healing is a possible mechanism of
      keloid formation.
AB  - Keloids are a hyperproliferative response of connective tissue in response to
      trauma. The mechanism by which this occurs is poorly understood and currently no
      successful treatment exists. HYPOTHESIS: Senescent fibroblasts form during wound
      repair, as the result of oxidative stress. They have a major role in the control
      of fibroblast proliferation and extracellular matrix synthesis, acting as
      inhibitors. The defective induction of stress-induced senescent phenotype (SIPS)
      creates an insufficient number of senescent cells, diminishing the inhibitor
      effect, causing the uncontrolled hyperproliferation and keloid formation. In the
      proposed mechanism of keloid formation, fibroblasts have a major role, but it is
      also possible that other cells are involved, like keratinocytes and melanocytes.
      Accepting the hypothesis to be correct, a therapy that induces senescence can be
      used to prevent the keloid formation. Current therapies are only partially
      effective because they either induce senescence in too few cells or in enough
      number of cells, but at the same time inducing death (apoptosis and necrosis) of
      other cells. Dead cells are probably the source of a new repair cycle
      (proliferation), therefore the process of keloid formation is only postponed but
      not blocked. A more efficient prevention of keloid formation could be achieved
      using specific drugs or physical methods that induce senescence and not cell
      death. Therapies based on photodynamic and PUVA therapy, capable to induce
      predominantly cell senescence, can be possibly effective. The magnitude of
      oxidative stress, created during photodynamic therapy, can be reduced and used to
      produce sublethal doses, to cause senescence instead of cell death. Except
      standard photosensitizers, other drugs could be used, that are not so powerful in
      inducing oxidative stress, i.e. amphotericin B in combination with UV light.

PMID- 16278055
TI  - Characterization of ISLpl4, a functional insertion sequence in Lactobacillus
      plantarum.
AB  - A Lactobacillus plantarum strain, CECT 4645, was found to have insertions of a
      sequence (985 bp in length) at least in eight loci in its genome. The prototype
      copy (Lp1) of this insertion sequence (named ISLpl4) has one open reading frame
      encoding a putative protein that is 292 amino acids in length with significant
      levels of similarity with IS982 family transposases. Perfect 16-bp inverted
      repeats were found at its termini. Upon transposition, generates 8-bp direct
      repeats of the target sequence, but no consensus sequences could be identified at
      either insertion site. The ISLpl4 pattern changed over many generations on the
      CECT 4645 strain. This finding strongly supports our hypothesis that ISLpl4 is a
      functional element in L. plantarum. Some of these elements may be cryptic, since
      point mutation or 1-nucleotide deletions were found in their transposase encoding
      genes. ISLpl4 copies have been detected in Leuconostoc mesenteroides, Oenococcus
      oeni, and Lactobacillus sakei. An ISLpl4 copy of O. oeni contained a +1
      nucleotide insertion on its transposase encoding gene and, by using an
      experimental system, we were able to demonstrate that this specific sequence
      originates a +1 programmed translational frameshifting. Although the
      frameshifting process reported here operates at a low rate, this description
      might represent the first case of a functional +1 frameshifting among IS.

PMID- 16278056
TI  - Validation of fluorescence polarization assay (FPA) and comparison with other
      tests used for diagnosis of B. melitensis infection in sheep.
AB  - Fluorescence polarization assay (FPA) is a new test for the serological diagnosis
      of Brucella spp. infection in animals. The FPA is validated for the diagnosis of
      B. melitensis infection in sheep. For this purpose, 166 sera originated from
      natural infected sheep (verified by culture) and 851 sera originated from healthy
      animals (reared in areas where B. melitensis was never been isolated) were
      tested. The optimum cut-off value that offers the highest diagnostic sensitivity
      (DSn) and diagnostic specificity (DSp) was determined at 87mP with the use of ROC
      analysis. The DSn and DSp of FPA using this cut-off value are calculated at 97.6
      and 98.9% with a 95% confidence interval (CI) of 93.9-99.3% and 98.0-99.5%,
      respectively. The DSn and DSp of FPA have been assessed also using as positive
      reference (n=587), sera that gave positive results at least in two tests used for
      diagnosis of B. melitensis in sheep as Rose Bengal Test (RBT), modified Rose
      Bengal Test (m-RBT), complement fixation test (CFT), indirect Elisa (i-Elisa) and
      competition Elisa (c-Elisa) originated from animals reared in flocks infected by
      B. melitensis. The optimum cut-off value using the above panel of positive
      reference sera was the same offering a DSn of 95.9% with a 95% CI, 94.0-97.4%,
      since the DSp remains the same. The DSn and DSp as well as performance, accuracy
      and agreement of FPA's result were compared with those of other tests used. The
      accuracy of FPA is very high, similar with that of i-Elisa. FPA is a promising
      assay, which offers a DSn and accuracy better that of those of the tests
      currently approved for the diagnosis of B. melitensis in sheep and goats. Due to
      its simplicity, the sort time that results can be obtained and its accuracy it
      can be used and improve the laboratory testing capacity as well as the efficacy
      of the eradication program based on test-and-slaughter policy.

PMID- 16278057
TI  - Optimal strategies for newborn ventilation--a synthesis of the evidence.
AB  - A variety of ventilation modes are available for the newborn. Although, there
      have been randomised trials assessing certain modes, these have generally only
      included prematurely born infants with RDS or infants with severe respiratory
      failure. Meta-analysis of the results of those trials has demonstrated that
      neither patient triggered nor high frequency oscillatory ventilation is
      advantageous for the prematurely born infant with RDS, but extracorporeal
      membrane oxygenation increases survival in infants with severe respiratory
      failure. Appropriately designed studies are required to determine the role of
      newer ventilation modes and whether forms of respiratory support avoiding
      intubation are less injurious to the lungs. Research should also focus on infants
      with other respiratory disorders, particularly BPD. Prior to further randomised
      trials being undertaken, it is essential that the optimum method of applying each
      ventilator mode is identified and it is clearly understood whether differences in
      ventilator/oscillator performance influence outcome.

PMID- 16278058
TI  - Cystic fibrosis in neonates and infants.
AB  - Cystic fibrosis (CF) is a common autosomal recessive disorder, characterized by
      chronic bronchopulmonary infection, pancreatic insufficiency, and subsequently,
      other multisystem complications. Most children are diagnosed before school age.
      Here we review the pathophysiology of the condition, the age-related
      presentations of CF up until school age, and the appropriate use of diagnostic
      tests. A specialist centre should supervise treatment. There are exciting new
      advances in monitoring techniques in the preschool years, including CT scanning,
      bronchoscopy and gas mixing indices. Recent advances in the knowledge of the
      molecular biology of CF hold out the hope of specific therapies which can reverse
      the underlying defect causing death from CF lung disease.

PMID- 16278059
TI  - Breast milk and cytomegalovirus infection in preterm infants.
AB  - The incidence of postnatal human cytomegalovirus (HCMV) reactivation during
      lactation equals the maternal seroprevalence. Infectious virus, viral DNA and RNA
      can be isolated from cells and fat free milk whey. Early onset of viral DNAlactia
      and virolactia as well as high viral load in milk whey are maternal risk factors
      for virus transmission. Preterm infants below 1000 g birthweight and a
      gestational age below 30 weeks may be at high risk of acquiring a symptomatic
      HCMV infection. Several recent studies using frozen milk for feeding describe low
      transmission rates and mostly asymptomatically infected neonates. However despite
      different freeze-storing procedures HCMV transmission occurred and severe HCMV
      infections were observed. Only few data exist on the long-term outcome of
      postnatally acquired HCMV infection via breast milk. Additional long-term outcome
      studies are needed. The newly developed short-term pasteurisation may be a
      reliable alternative to freezing and Holder pasteurisation, since important milk
      constituents are conserved.

PMID- 16278060
TI  - The diagnosis and management of gastro-oesophageal reflux in infants.
AB  - Gastro-oesophageal reflux (GOR) and gastro-oesophageal reflux disease (GORD)
      occur frequently during the first months of life. Gastro-oesophageal reflux may
      be a primary gastro-intestinal motility disorder, but it may also be secondary to
      other conditions such as cow's milk protein allergy. Objective diagnosis can be
      difficult because there may be absence of correlation between history, results of
      pH monitoring and histology. Severe GORD may cause minor symptoms, and minor GOR
      may cause severe symptoms. Several different therapeutic interventions exist.
      Simply stated, thickened formula reduces regurgitation and alginates and proton
      pump inhibitors can be used to decrease acid GOR, depending on the severity of
      the GORD. Efficacy data of prokinetic drugs are either lacking or disappointing.
      Regarding side-effects, interest has been focused on cisapride, although other
      molecules have similar effects. Long-term side-effects such as the nutritional
      consequence of therapeutic management have been insufficiently studied,
      especially for the acid-reducing molecules.

PMID- 16278061
TI  - Genotoxic effects of chromium(VI) and cadmium(II) in human blood lymphocytes
      using the electron microscopy in situ end-labeling (EM-ISEL) assay.
AB  - Evaluation of genotoxic effects of potassium chromate (K2CrO4) and cadmium
      chloride (CdCl2) was carried out in human blood lymphocytes in vitro as measured
      by the electron microscopy in situ end-labeling (EM-ISEL). EM-ISEL was used to
      assess DNA single-strand breaks (SSBs) expressed as number of immunogold
      particles per microm2 of chromatin at both chromosomal and nuclear DNA levels.
      Human lymphocytes were cultured in supplemented RPMI medium for 72 h including
      treatment for 2 h with K2CrO4 (0-150 microM), CdCl2 (0-150 microM) or methyl
      methanesulfonate (500 microM) as a positive control. Quantification of SSBs by EM
      ISEL showed that both compounds are genotoxic agents at non-cytotoxic
      concentrations. This study brings new information on the utility of EM-ISEL for
      the evaluation of genotoxicity and confirms the genotoxic effects induced by
      chromium and cadmium.

PMID- 16278062
TI  - A cross-sectional study of the characteristics and determinants of emergency care
      utilization among people with intellectual disabilities in Taiwan.
AB  - AIMS: The purpose of this study was to identify health characteristics of people
      with intellectual disabilities (ID) and to assess the use of emergency care
      facilities by these people and factors affecting this utilization. METHOD: A
      cross-sectional study was employed. Subjects were recruited from the Taiwan
      National Disability Registration System. A total of 1071 people registered with
      ID in Taiwan were recruited for this study in 2001. Data were collected via a
      structured mail-out questionnaire that was completed by the main carers of people
      with ID. RESULTS: Most of the carers subjectively characterized the overall
      health status of people with ID as good-excellent. However, people with ID carry
      a burden of diseases greater than that of the general population. Nearly half
      (47.7%) of the subjects reported having an illness in the past 7 months. Most of
      the morbidity was associated with neurological, psychiatric, digestive,
      dermatological and cardiovascular diseases or disorders. One-third of subjects
      took medication regularly and 15% were 'Major Illness' card beneficiaries of the
      Taiwan National Health Insurance scheme. About two-thirds of individuals with ID
      were classified as having multiple disabilities and 24.5% needed to be provided
      with frequent rehabilitative therapies to maintain their normal daily functions.
      Respondents indicated that 18.4% of the subjects had used emergency care in the
      past 7 months. A stepwise logistic regression model highlighted that the
      following need factors were significantly related to the utilization of emergency
      care: having an illness (OR=2.1, 95% CI=1.2-3.6), taking medicine regularly
      (OR=1.8, 95% CI=1.1-2.9) and self-reported health status (poor health: OR=9.9,
      95% CI=2.1-45.7; bad health: OR=8.2, 95% CI=1.3-49.8). CONCLUSIONS: To ensure
      that people with ID minimize their utilization of emergency care, it is necessary
      to establish in appropriate community systems to monitor individuals with ID with
      poor health status, diseases and who take medicine regularly.

PMID- 16278063
TI  - A method for 3D reconstruction of coronary arteries using biplane angiography and
      intravascular ultrasound images.
AB  - The aim of this study is to describe a new method for the three-dimensional
      reconstruction of coronary arteries and its quantitative validation. Our approach
      is based on the fusion of the data provided by intravascular ultrasound images
      (IVUS) and biplane angiographies. A specific segmentation algorithm is used for
      the detection of the regions of interest in intravascular ultrasound images. A
      new methodology is also introduced for the accurate extraction of the catheter
      path. In detail, a cubic B-spline is used for approximating the catheter path in
      each biplane projection. Each B-spline curve is swept along the normal direction
      of its X-ray angiographic plane forming a surface. The intersection of the two
      surfaces is a 3D curve, which represents the reconstructed path. The detected
      regions of interest in the IVUS images are placed perpendicularly onto the path
      and their relative axial twist is computed using the sequential triangulation
      algorithm. Then, an efficient algorithm is applied to estimate the absolute
      orientation of the first IVUS frame. In order to obtain 3D visualization the
      commercial package Geomagic Studio 4.0 is used. The performance of the proposed
      method is assessed using a validation methodology which addresses the separate
      validation of each step followed for obtaining the coronary reconstruction. The
      performance of the segmentation algorithm was examined in 80 IVUS images. The
      reliability of the path extraction method was studied in vitro using a metal wire
      model and in vivo in a dataset of 11 patients. The performance of the sequential
      triangulation algorithm was tested in two gutter models and in the coronary
      arteries (marked with metal clips) of six cadaveric sheep hearts. Finally, the
      accuracy in the estimation of the first IVUS frame absolute orientation was
      examined in the same set of cadaveric sheep hearts. The obtained results
      demonstrate that the proposed reconstruction method is reliable and capable of
      depicting the morphology of coronary arteries.

PMID- 16278064
TI  - Infections and autoimmune diseases.
AB  - The high percentage of disease-discordant pairs of monozygotic twins demonstrates
      the central role of environmental factors in the etiology of autoimmune diseases.
      Efforts were first focussed on the search for triggering factors. The study of
      animal models has clearly shown that infections may trigger autoimmune diseases,
      as in the case of Coxsackie B4 virus in type I diabetes and the
      encephalomyocarditis virus in autoimmune myositis, two models in which viruses
      are thought to act by increasing immunogenicity of autoantigens secondary to
      local inflammation. The induction of a Guillain-Barre syndrome in rabbits after
      immunization with a peptide derived from Campylobacter jejuni is explained by
      mimicry between C. jejuni antigens and peripheral nerve axonal antigens. Other
      models involve chemical modification of autoantigens, as in the case of iodine
      induced autoimmune thyroiditis. These mechanisms have so far only limited
      clinical counterparts (rheumatic fever, Guillain-Barre syndrome and drug-induced
      lupus or myasthenia gravis) but one may assume that unknown viruses may be at the
      origin of a number of chronic autoimmune diseases, such as type I diabetes and
      multiple sclerosis) as illustrated by the convergent data incriminating IFN-alpha
      in the pathophysiology of type I diabetes and systemic lupus erythematosus.
      Perhaps the difficulties met in identifying the etiologic viruses are due to the
      long lag time between the initial causal infection and onset of clinical disease.
      More surprisingly, infections may also protect from autoimmune diseases. Western
      countries are being confronted with a disturbing increase in the incidence of
      most immune disorders, including autoimmune and allergic diseases, inflammatory
      bowel diseases, and some lymphocyte malignancies. Converging epidemiological
      evidence indicates that this increase is linked to improvement of the socio
      economic level of these countries, posing the question of the causal relationship
      and more precisely the nature of the link. Epidemiological and clinical data
      support the hygiene hypothesis according to which the decrease of infections
      observed over the last three decades is the main cause of the incessant increase
      in immune disorders. The hypothesis does not exclude an etiological role for
      specific pathogens in a given immune disorder as might notably be the case in
      inflammatory bowel diseases. Even in this setting, infections could still have a
      non-specific protective role. Independently of the need for confirmation by
      epidemiological prospective studies, the hygiene hypothesis still poses numerous
      questions concerning the nature of protective infectious agents, the timing of
      their involvement with regard to the natural history of immune diseases and, most
      importantly, the mechanisms of protection. Four orders of mechanisms are being
      explored. Antigenic competition is the first hypothesis (immune responses against
      pathogens compete with autoimmune and allergic responses). This is probably an
      important mechanism but its modalities are still elusive in spite of considerable
      experimental data. Its discussion in the context of homeostatic regulation of
      lymphocyte pools has shed new light on this hypothesis with possible competition
      for self MHC peptide recognition and interleukin-7. Another hypothesis deals with
      immunoregulation. Infectious agents stimulate a large variety of regulatory cells
      (Th2, CD25+, Tr1, NKT, ...) whose effects extend to other specificities than
      those which triggered their differentiation (bystander suppression). Infectious
      agents may also intervene through components which are not recognized as antigens
      but bind to specific receptors on cells of the immune system. Major attention has
      recently been drawn to Toll receptors (expressed on macrophages and possibly on
      regulatory T cells) and TIM proteins present on Th cells, which may express the
      function of the virus receptor (as in the case of the Hepatitis A virus and Tim
      1). Experimental data will be presented to support each of these hypotheses. In
      any event, the final proof of principle will be derived from therapeutic trials
      where the immune disorders in question will be prevented or better cured by
      products derived from protective infectious agents. Numerous experimental data
      are already available in several models. Preliminary results have also been
      reported in atopic dermatitis using bacterial extracts and probiotics.

PMID- 16278065
TI  - Induction of cytosolic phospholipase A2 by lipopolysaccharide in canine tracheal
      smooth muscle cells: involvement of MAPKs and NF-kappaB pathways.
AB  - Cytosolic phospholipase A2 (cPLA2) plays a pivotal role in mediating agonist
      induced arachidonic acid (AA) release for prostaglandins (PG) synthesis induced
      by bacterial lipopolysaccharide (LPS) and cytokines. However, the intracellular
      signaling pathways mediating LPS-induced cPLA2 expression and PGE2 synthesis in
      canine tracheal smooth muscle cells (TSMCs) remains unknown. LPS-induced
      expression of cPLA2 and release of PGE2 was attenuated by inhibitors of tyrosine
      kinase (genistein), phosphatidylcholine-phospholipase C (D609),
      phosphatidylinositol-phospholipase C (U73122), PKC (GF109203X and staurosporine),
      removal of Ca2+ by BAPTA/AM plus EDTA, MEK1/2 (PD98059), p38 (SB202190), JNK
      (SP600125), and phosphatidylinositol 3-kinase (PI3-K; LY294002 and wortmannin).
      The involvement of MPAKs in LPS-induced responses was further confirmed by
      transfection of TSMCs with dominant negative mutants of ERK2 and p38. LPS-induced
      cPLA2 expression and PGE2 synthesis was inhibited by a selective NF-kappaB
      inhibitor (helenalin) and transfection with dominant negative mutants of NF
      kappaB inducing kinase (NIK), IkappaB kinase (IKK)-alpha, and IKK-beta,
      consistent with that LPS-stimulated both IkappaB-alpha degradation and NF-kappaB
      translocation into nucleus in these cells. LPS-stimulated cPLA2 phosphorylation
      was inhibited by PD98059, GF109203X, and staurosporine, indicating the regulation
      by p42/p44 MAPK and PKC. Moreover, LPS-induced up-regulation of cPLA2 and COX-2
      linked to PGE2 synthesis was inhibited by AACOCF3 (a selective cPLA2 inhibitor),
      implying the involvement of cPLA2 in these responses. These findings suggest that
      phosphorylation and expression of cPLA2 correlates with the release of PGE2 from
      LPS-challenged TSMCs, at least in part, mediated through MAPKs and NF-kappaB
      signaling pathways. LPS-mediated responses were modulated by PLC, Ca2+, PKC,
      tyrosine kinase, and PI3-K in TSMCs.

PMID- 16278066
TI  - Temporomandibular joint morphology following post-traumatic ankylosis in 26
      patients.

PMID- 16278067
TI  - Effects of tea polyphenols on telomerase activity of a tongue cancer cell line: a
      preliminary study.
AB  - The aim of this study was to determine, at the mRNA and protein levels, whether
      tea polyphenols (TPs) affect the expression of the human telomerase reverse
      transcriptase (hTERT) gene in the Tca8113 cancerous cell line. The expression of
      this gene was determined at the mRNA level by reverse transcription and
      polymerase chain reaction and at the protein level by Western blotting. The semi
      quantitative scores of hTERT mRNA expression were analyzed by one-way analysis of
      variance. After 72 h of exposure to TPs, the mean (+/-SD) scores of hTERT mRNA
      expression in TP 0.1g/l, TP 0.05 g/l and a control group were 0.32+/-0.05, 0.41+/
      0.04 and 0.72+/-0.05, respectively (P<0.05). The Western blot assay showed that
      TPs also decreased the expression of hTERT at the protein level. These results
      indicate that TPs reduce hTERT activity in the human Tca8113 cell line in a time-
      and dose-dependent manner, disabling telomerase activity and thereby terminating
      unlimited cancer cell proliferation. These findings suggest a mechanism behind
      TP's anticancer activity.

PMID- 16278068
TI  - Facial emphysema caused by cheek bite.
AB  - Biting of the buccal mucosa is very frequent injury, whereas facial emphysema
      caused by cheek bite is rare. We report a case of facial emphysema causing
      puffing of the cheek through a self-inflicted bite of the buccal mucosa.

PMID- 16278069
TI  - Analgesic efficacy of aceclofenac after surgical extraction of impacted lower
      third molars.
AB  - The analgesic efficacy of aceclofenac in the control of pain after surgical
      extraction of impacted mandibular third molars was compared with its preoperative
      administration. Two groups of 20 patients each were medicated with 2 tablets of
      100 mg aceclofenac taken orally either 1h before surgery or in the early
      postoperative period. All surgeries were performed by the same surgeon and the
      surgical technique was the same for all patients. Pain was assessed with a Visual
      Analogue Scale and a 0-4 Scale, as well as by counting the number of analgesic
      drug tablets taken after the surgery. Patients in the preoperative group took
      fewer tablets postoperatively and had a lower pain score both in the Visual
      Analogue Scale and the 0-4 Scale. This difference, however, was statistically
      significant only at 6h after surgery, which is the time of maximum pain for this
      surgical procedure. Aceclofenac was more efficient in controlling pain when
      administered before the surgery.

PMID- 16278070
TI  - Metastatic uterine leiomyosarcoma masquerading as a primary lesion of the
      masseter muscle.
AB  - Leiomyosarcomas are malignant tumours of smooth muscle origin. These tumours are
      very rare in the head and neck region. We report a case of metastatic uterine
      leiomyosarcoma masquerading as a primary sarcoma of the masseter muscle. We
      highlight the importance of considering the possibility of an unrecognised
      primary abdominal or uterine tumour.

PMID- 16278071
TI  - Primary tuberculous osteomyelitis of zygoma.
AB  - Osteomyelitis of zygomatic bone is rare, and tuberculous osteomyelitis is even
      rarer. This is the case report of a 3-year-old child presenting with a
      discharging sinus and swelling on the zygoma, which was initially thought to be
      orbital cellulitis. After further examination, she was diagnosed as having
      tuberculosis of zygoma and responded to anti-tubercular chemotherapy.

PMID- 16278072
TI  - Re: Dimitroulis, G. The role of surgery in the management of disorders of the
      temporomandibular joint: a critical review of the literature. Part 2. Int J Oral
      Maxillofac Surg 2005: 34: 231-237.

PMID- 16278073
TI  - Tracking methicillin-resistant Staphylococcus aureus clones in Colombian
      hospitals over 7 years (1996-2003): emergence of a new dominant clone.
AB  - Worldwide dissemination of methicillin-resistant Staphylococcus aureus (MRSA)
      clones is a well-characterised phenomenon. Two hundred isolates of MRSA recovered
      from 17 Colombian hospitals collected between 2001 and 2003 were characterised by
      pulsed-field gel electrophoresis (PFGE). A new dominant electrophoretic pattern
      unrelated to previously characterised clones in Colombia was detected in 137
      (68.5%) of these isolates. Only 40 (20%) isolates still showed a pattern closely
      related to a previously described dominant clone. The new electrophoretic pattern
      was indistinguishable from a cluster of isolates recovered in Chile between 1996
      and 1998. Isolates from this clonal cluster exhibited multidrug resistance but
      were susceptible to linezolid and glycopeptides. The results indicate a shift in
      the population genetics of Colombian MRSA and confirm dissemination of the
      Chilean clone for the first time.

PMID- 16278074
TI  - Dopamine D2 receptor gene variants and quantitative measures of positive and
      negative symptom response following clozapine treatment.
AB  - OBJECTIVE: Explore relationships between 12 dopamine D2 gene variants and
      quantitative measures of positive and negative symptom response following
      clozapine treatment in two treatment refractory or intolerant populations
      (Caucasian and African-American). EXPERIMENTAL PROCEDURES: Subjects included 97
      Caucasian and 35 African-American DSM-III-R or DSM-IV schizophrenics and were
      genotyped by 5'-exonuclease fluorescence assays. Genotype, allele +/- and
      haplotype groups were compared on Brief Psychiatric Rating Scale (BPRS) overall,
      positive (BPOS) and negative symptom subscales (BNEG) using analysis of variance.
      RESULTS: In Caucasians, no significant associations were found for any individual
      polymorphisms or haplotypes. In African-Americans, the TaqIB B2 (T) allele and
      rs1125394 allele 1 (A), and a two-marker haplotype containing these two alleles
      were associated with improvement in overall BPRS and BPOS response. CONCLUSIONS:
      Variability in clozapine response is still not fully understood and likely
      involves multiple factors. This study suggests that D2 receptor gene variants may
      be among such factors.

PMID- 16278075
TI  - Caffeine modulates P50 auditory sensory gating in healthy subjects.
AB  - The P50 suppression paradigm is an index of sensory gating assumed to reflect an
      inhibitory process. Adenosine is a neuromodulator with mostly inhibitory activity
      that is released by physiological stimuli and can be blocked by non-selective
      adenosine receptor antagonists such as theophylline and caffeine. A previous
      study showed that a single dose of theophylline decreased P50 suppression in
      healthy volunteers. Here we investigated the effect of caffeine (0, 100, 200 and
      400 mg p.o.) on P50 sensory gating in 24 healthy volunteers (15 habitual caffeine
      high-users and 9 low-users). The 200 and 400 mg doses reduced P50 gating, whereas
      100 mg produced a non-significant effect. The effect of caffeine was independent
      of gender and habitual caffeine intake. High caffeine users also showed baseline
      differences, with lower S(2) amplitudes compared to low-users. These results
      reinforce the participation of adenosine in the modulation of P50 sensory gating
      and suggest that caffeine ingestion should be controlled for in the P50 sensory
      gating paradigm.

PMID- 16278076
TI  - Mitochondrial dysfunction in cardiac ischemia-reperfusion injury: ROS from
      complex I, without inhibition.
AB  - A key pathologic event in cardiac ischemia reperfusion (I-R) injury is
      mitochondrial energetic dysfunction, and several studies have attributed this to
      complex I (CxI) inhibition. In isolated perfused rat hearts, following I-R, we
      found that CxI-linked respiration was inhibited, but isolated CxI enzymatic
      activity was not. Using the mitochondrial thiol probe iodobutyl
      triphenylphosphonium in conjunction with proteomic tools, thiol modifications
      were identified in several subunits of the matrix-facing 1alpha sub-complex of
      CxI. These thiol modifications were accompanied by enhanced ROS generation from
      CxI, but not complex III. Implications for the pathology of cardiac I-R injury
      are discussed.

PMID- 16278077
TI  - Role of tyrosine-57 and -65 in membrane-damaging and sphingomyelinase activities
      of Clostridium perfringens alpha-toxin.
AB  - Clostridium perfringens alpha-toxin (370 residues) is a major virulence factor in
      the pathogenesis of gas gangrene. The toxin is composed of an N-terminal domain
      (1-250 residues) where lies the catalytic site and a C-terminal domain (251-370
      residues), the Ca(2+)-binding domain, responsible for binding to membranes. The
      role of Tyr-57 and Tyr-65 close to the catalytic pocket (site) in the N-domain
      was investigated. Replacement of Tyr-57 and -65 with alanine, leucine, or
      phenylalanine did not affect the sphingomyelinase activity of the toxin for
      sodium deoxycholate-solubilized shingomyelin. However, the substitution of Tyr-57
      and -65 with alanine or leucine resulted in a radical reduction in the hemolysis
      of sheep erythrocytes, the release of carboxyfluorescein from shingomyelin
      cholesterol (1:1) liposomes, and a significant decrease in binding to the
      liposomes. The binding of variant toxins, Y57C/C169L and Y65C/C169L, labeled with
      the environmentally sensitive fluorophore, acrylodan, to the liposomes suggested
      insertion of the variants in a hydrophobic environment in the bilayer. These
      observations suggested that Tyr-57 and -65 play a role in the penetration of the
      toxin into the bilayer of membranes and access of the catalytic site to
      sphingomyelin in membranes, but do not participate in the enzymatic activity.

PMID- 16278078
TI  - XBP1 forms a regulatory loop with BMP-4 and suppresses mesodermal and neural
      differentiation in Xenopus embryos.
AB  - The active form of the Xenopus X-box binding protein 1 (xXBP1) partially
      synergizes and partially antagonizes with BMP-4 signaling. xXBP1 overexpression
      inhibits mesoderm differentiation and formation of neural tissues. A functional
      knockdown promotes differentiation of lateral and dorsal mesoderm but not of
      ventral mesoderm and of neuroectoderm. We show that the active form of xXBP1 in
      gastrula and early neurula stage embryos is generated by removal of exon 4 and
      not by an endoribonuclease activity in the endoplasmic reticulum. The N-terminal
      region of xXBP1 which contains the basic leucine-zipper also contains a nuclear
      localization signal and both, the N-terminal as well as the C-terminal regions
      are required for xXBP1 function. The effects of xXBP1 are in part correlated to a
      regulatory loop between xXBP1 and BMP-4. xXBP1 and BMP-4 stimulate mutually the
      transcription of each other, but xXBP1 inhibits the BMP-4 target gene, Xvent-2.
      Both, in vitro and in vivo assays demonstrate that xXBP1 interacts with BMP-4 and
      Xvent-2B promoters. GST-pulldown assays reveal that xXBP1 can interact with c
      Jun, the transcriptional co-activator p300 and with the BMP-4 responsive Smad1.
      On the other hand, xXBP1 also binds to the inhibitory Smads, Smad6 and Smad7,
      that can act as transcriptional co-repressors. Based on these data, we conclude
      that xXBP1 might function as an inhibitor of mesodermal and neural tissue
      formation by acting either as transcriptional activator or as repressor. This
      dual activity depends upon binding of co-factors being involved in the formation
      of distinct transcription complexes.

PMID- 16278079
TI  - Development of chronic hypoventilation in amyotrophic lateral sclerosis patients.
AB  - Early prediction of respiratory muscle involvement and chronic hypoventilation
      (CH) in amyotrophic lateral sclerosis (ALS) patients can help to plan mechanical
      ventilatory aids and palliative care interventions well before respiratory
      failure occurs. To describe the natural history of the progressive pulmonary
      dysfunction leading to CH, and to identify potential parameters associated with
      its development in ALS, we prospectively followed 38 ALS patients up to 26
      months, starting from their first presentation at our Clinic. At study entry,
      median FVC was 87% (interquartile range: 72-104%) and declined by 10% after 6
      months (range: 2-49%), showing a very high inter-patient variability. Over the 26
      months follow-up, 19 patients (50%) presented CH in the first 12 months, and
      eight patients (21%) developed CH in the remaining 14 months of the study. The
      remaining 29% of patients did not show signs of CH during the whole period of
      observation. In the Cox model, the category of disease progression (rapid vs.
      intermediate and slow), assessed using the Appel ALS Rating Scale (AARS) in the
      first 3 months after presentation, was the only variable associated with a
      significantly increased likelihood of CH. We conclude that CH can occur within 1
      year from presentation in a great proportion of patients, independently from
      their initial respiratory status. Including the patients in specific categories
      of early disease progression, as assessed with the AARS, could be a sensitive
      method to identify patients with different risk of developing CH, and may help
      physicians to more efficiently plan the frequencies of respiratory evaluations,
      initiate mechanical ventilation and discuss advance directives with the patients
      and their caregivers.

PMID- 16278080
TI  - Immunological consequences of three doses of heat-killed Mycobacterium vaccae in
      the immunotherapy of tuberculosis.
AB  - We report the first study of triple-dose immunotherapy with heat-killed
      Mycobacterium vaccae (SRL 172) combined with short-course, directly observed
      chemotherapy in newly diagnosed pulmonary tuberculosis patients. The study was
      carried out in Rosario, Argentina, where single-dose immunotherapy with M. vaccae
      has previously been shown effective. Twenty-two HIV seronegative patients, sputum
      positive for tubercle bacilli, entered a randomised and partly blinded trial.
      Twelve patients received injections of SRL 172 and 10 patients received placebo
      on days 1, 30 and 60 of chemotherapy. All patients were followed up clinically,
      by sputum bacteriology, chest radiography and haematology. Patients receiving SRL
      172 showed faster and more complete clinical improvement, accelerated
      disappearance of bacilli from sputum, better radiological clearance and a more
      rapid fall in ESR, than did those receiving placebo. Follow-up continued for a
      year after therapy and no patient failed treatment or relapsed. Special
      investigations included longitudinal assessments of respiratory bursts and
      expression of CD11b on separated polymorphonuclear and mononuclear leukocytes.
      Tumour necrosis factor alpha (TNF-alpha) was measured in the supernates of
      cultured cells and both TNF-alpha and interleukin-4 (IL-4) were measured in serum
      samples. Immunotherapy recipients showed a significantly faster return towards
      normal values in all the immunological parameters, than did placebo recipients.
      The results are consistent with a regulatory activity on cellular immunity,
      reducing the influence of Th2 and enhancing Th1 to the benefit of the patients.
      This could allow a reduced period of chemotherapy without loss of efficacy and
      help to prevent the development of multi-drug resistance.

PMID- 16278081
TI  - Clinical co-morbidities in obstructive sleep apnea syndrome treated with
      mandibular repositioning appliance.
AB  - INTRODUCTION: Intraoral mandibular repositioner appliances (IOMRAs) are designed
      to enlarge pharyngeal airway space advancing the mandible and increasing
      genioglossus tone during sleep. Obstructive sleep apnea syndrome (OSAS) treatment
      with IOMRAs is beneficial, but there is a lack of studies in the literature
      defining the target population more inclined to respond to this treatment.
      METHODS: We contacted by telephone 188 previously treated patients with IOMRA,
      detecting 20 not improved patients (Study Group). Twenty improved patients of the
      remaining 168 were randomly paired according to gender, age, apnea, and hypopnea
      index as Control Group. Both groups answered questionnaires for diagnosis of
      sleep disorders, depression, anxiety, and the Epworth sleepiness scale. We did a
      descriptive and inferential statistical analysis. The inferential analysis was
      divided into two steps: univariate analysis using Fischer exact test and a
      multiple inferential analysis using a stepwise regression model. RESULTS:
      Although the final model included only insomnia, we concluded that the presence
      of gastric, neurological and rheumatic diseases also tended to be associated with
      the self-perception of non-improvement. The association between the accumulation
      of gastric, neurological, and rheumatic diseases and insomnia and improvement
      demonstrated that an increase in one of these diseases correspond to a two-fold
      increase in the chance of non-improvement. CONCLUSIONS: Insomnia was the most
      important factor compromising the success of OSAS treatment with IOMRAs, and the
      isolated presence of gastric, neurological and rheumatic diseases, but especially
      their combination, reduces the perception rate of well-succeeded treatment with
      IOMRAs.

PMID- 16278082
TI  - Determinants of false positive recall in an Australian mammographic screening
      program.
AB  - We conducted a case-control study (n=30128) to assess the importance of clinical
      (e.g., family history, age, hormone replacement therapy (HRT) use and duration)
      and service-related characteristics (e.g., time since introduction of Kodak
      MINR2000 film, year of screen) for false positive (FP) recall at BreastScreen
      Victoria, Australia. There was an age-adjusted upward trend in FP recall rates
      with year of screen at first (odds ratio (OR) 1.11, 95% confidence interval (95%
      CI) 1.08-1.13) and subsequent rounds (OR 1.04, 95% CI 1.01-1.06). In the
      multivariate analysis, the upward trend only remained for first round and age and
      family history also remained statistically significant at first round. At
      subsequent rounds the time since introduction of MINR2000, age, strong family
      history of breast cancer, use of HRT, recall at previous screen and previous
      screen at more than 27 months were all important predictors of FP recall. The
      rise in FP rates with year of screen at first round screening is of concern and
      may require further training of radiologists to improve confidence when viewing
      films when there a no films for comparison.

PMID- 16278083
TI  - Defective neuromuscular synaptogenesis in mice expressing constitutively active
      ErbB2 in skeletal muscle fibers.
AB  - We overexpressed a constitutively active form of the neuregulin receptor ErbB2
      (CAErbB2) in skeletal muscle fibers in vivo and in vitro by tetracycline
      inducible expression. Surprisingly, CAErbB2 expression during embryonic
      development was lethal and impaired synaptogenesis yielding a phenotype with loss
      of synaptic contacts, extensive axonal sprouting, and diffuse distribution of
      acetylcholine receptor (AChR) transcripts, reminiscent of agrin-deficient mice.
      CAErbB2 expression in cultured myotubes inhibited the formation and maintenance
      of agrin-induced AChR clusters, suggesting a muscle- and not a nerve-origin for
      the defect in CAErbB2-expressing mice. Levels of tyrosine phosphorylated MuSK,
      the signaling component of the agrin receptor, were similar, while tyrosine
      phosphorylation of AChRbeta subunits was dramatically reduced in CAErbB2
      expressing embryos relative to controls. Thus, a gain-of-function manipulation of
      ErbB2 signaling pathways renders an agrin-deficient-like phenotype that uncouples
      MuSK and AChR tyrosine phosphorylation.

PMID- 16278084
TI  - The prion protein requires cholesterol for cell surface localization.
AB  - The cellular prion protein PrP(c) is attached to the plasma membrane by a
      glycosyl-phosphatidyl-inositol (GPI-) anchor and is localized in lipid rafts,
      membrane microdomains characterized by a high content of sphingolipids and
      cholesterol. Previous studies revealed that perturbation of cholesterol synthesis
      prevents prion conversion, explained by redistribution of PrP(c) at the plasma
      membrane. We investigated the influence of inhibition of cholesterol synthesis by
      the HMG-CoA-reductase inhibitor mevinolin on the trafficking of PrP(c) in
      neuronal cells. Treatment with mevinolin significantly reduces the amount of
      surface PrP(c) and leads to its accumulation in the Golgi compartment. Analysis
      of mutant PrPs highlights the importance of the GPI-anchor for raft localization
      and provides information about domains implicated in lipid raft association of
      PrP in the secretory pathway. Our data show that cholesterol is essential for the
      cell surface localization of PrP(c), known to be necessary for prion conversion.

PMID- 16278085
TI  - Endogenous fluorescence imaging of somatosensory cortical activities after
      discrimination learning in rats.
AB  - Aerobic energy metabolism in the brain is reflected as changes in the green
      fluorescence of mitochondrial flavoproteins, and the activity-dependent changes
      in endogenous fluorescence are applicable for functional brain imaging. To
      understand the roles of cortical plasticity in discrimination learning, we used
      flavoprotein fluorescence imaging to visualize changes of neural activities in
      the rat primary somatosensory cortex (SI) after learning. Rats were trained to
      discriminate floor vibration at rewarded and unrewarded frequencies. After this
      discrimination learning was accomplished in 3-5 days, the rats were anesthetized
      with urethane (1.5 g/kg, i.p.), and neural responses were recorded in SI during
      flutter stimuli applied to the contralateral hindpaw. The fluorescence responses
      to the stimuli at unrewarded frequencies were selectively depressed in the
      trained rats, which had behaviorally neglected unrewarded stimuli. The depression
      of cortical responses was not observed in the rats trained with rewarded stimuli
      only. Therefore, the stimulus-specific depression in SI might explain a part of
      neural mechanisms underlying discrimination behavior. To reproduce the stimulus
      specific depression of cortical responses in anesthetized rats, tetanic cortical
      stimulation was paired with flutter stimulation applied to the hindpaw. Selective
      depression of fluorescence responses or field potentials in SI was induced by the
      paired stimulation. Our findings suggest that some intracortical circuits in SI
      are specifically tuned to and modulated by unrewarded stimuli of a particular
      frequency while SI neurons are responsive to both of rewarded and unrewarded
      stimuli. The present results indicate the usefulness of flavoprotein fluorescence
      imaging for investigating somatosensory cortical plasticity after learning.

PMID- 16278086
TI  - Noninvasive quantification of cerebral blood volume in humans during functional
      activation.
AB  - Like cerebral blood flow (CBF), cerebral blood volume (CBV) is an important
      physiological parameter closely associated with brain activity and thus,
      noninvasive quantification of CBV during brain activation provides another
      opportunity to investigate the relationship between neuronal activity and
      hemodynamic changes. In this paper, a new method is presented that is able to
      quantify CBV at rest and during activation. Specifically, using an inversion
      recovery pulse sequence, a set of brain images was collected at various inversion
      times (TIs). At each TI, functional images were acquired with a block-design
      visual stimulation paradigm. A biophysical model comprised of multiple tissue
      components was developed and was utilized for the determination of CBV using the
      visual stimulation data. MRI experiments on five healthy volunteers showed that
      CBV was 5.0 +/- 1.5 ml blood/100 ml brain during rest and increased to 6.6 +/-
      1.8 ml blood/100 ml brain following visual stimulation. Furthermore, experiments
      with visual stimulation at two frequencies (2 and 8 Hz) showed that the increases
      in CBV correlated with the strength of stimulation. This technique, with its
      ability to measure quantitative CBV values noninvasively, provides a valuable
      tool for quantifying hemodynamic signals associated with brain activation.

PMID- 16278087
TI  - Lack of GABABR1 gene variation (G1465A) in a Chinese population with temporal
      lobe epilepsy.
AB  - GABA(B) receptor1 (GABA(B)R1) gene is one of the susceptibility genes for
      temporal lobe epilepsy (TLE). Recently, it is reported that the GABA(B)R1
      polymorphism (G1465A) conferred a highly increased susceptibility to TLE. We
      performed a case-control study to confirm the findings. The study included a
      total of 112 nonlesional TLE patients and 124 controls of Chinese ancestry. Our
      study did not show any polymorphism in this locus, and suggested this
      polymorphism may not be a strong susceptibility factor for TLE among Chinese
      population.

PMID- 16278088
TI  - The LAM-SAFE Study: lamotrigine versus carbamazepine or valproic acid in newly
      diagnosed focal and generalised epilepsies in adolescents and adults.
AB  - OBJECTIVE: To investigate efficacy and safety of lamotrigine (LTG) versus
      carbamazepine (CBZ) or valproic acid (VPA) in newly diagnosed focal (FE) and
      idiopathic generalised (GE) epilepsies in adolescents and adults. METHODS: Open
      label randomised comparative multicentre 24-week monotherapy trial in newly
      diagnosed epilepsy patients of >or=12 years of age. Patients with FE were treated
      with LTG or CBZ, those with GE received LTG or VPA. The primary efficacy variable
      was the number of seizure-free patients during study weeks 17 and 24. RESULTS:
      Two hundred and thirty-nine patients were included. One hundred and seventy-six
      patients suffered from FE and 63 from GE. In the FE group, 88 patients each were
      treated with CBZ or LTG. Ninety-four percent of the CBZ patients and 89% of the
      LTG patients became seizure-free according to an intent-to-treat analysis (not
      statistically different). The rate of patients discontinuing treatment due to
      adverse events or a lack of efficacy was 19% with CBZ compared to 9% with LTG
      (not statistically different). In the GE group, 30 patients received VPA and 33
      LTG. During study weeks 17 and 24, 61% of the LTG patients and 84% of the VPA
      patients had become seizure-free (not statistically significant). The drop-out
      rate due to lack of efficacy or adverse events was 12% with LTG and 3% with VPA
      (not statistically different). CONCLUSIONS: This study indicates that the
      effectiveness of LTG in focal and generalised epilepsy syndromes as initial
      monotherapy in patients >or=12 years is in the range of standard first-line
      antiepileptic drugs.

PMID- 16278089
TI  - Sperm motility in fishes. (II) Effects of ions and osmolality: a review.
AB  - The spermatozoa of most fish species are immotile in the testis and seminal
      plasma. Therefore, motility is induced after the spermatozoa are released into
      the aqueous environment during natural reproduction or into the diluent during
      artificial reproduction. There are clear relationships between seminal plasma
      composition and osmolality and the duration of fish sperm motility. Various
      parameters such as ion concentrations (K+, Na+, and Ca2+), osmotic pressure, pH,
      temperature and dilution rate affect motility. In the present paper, we review
      the roles of these ions on sperm motility in Salmonidae, Cyprinidae,
      Acipenseridae and marine fishes, and their relationship with seminal plasma
      composition. Results in the literature show that: 1. K+ is a key ion controlling
      sperm motility in Salmonidae and Acipenseridae in combination with osmotic
      pressure; this control is more simple in other fish species: sperm motility is
      prevented when the osmotic pressure is high (Cyprinidae) or low (marine fishes)
      compared to that of the seminal fluid. 2. Cations (mostly divalent, such as Ca2+)
      are antagonistic with the inhibitory effect of K+ on sperm motility. 3. In many
      species, Ca2+ influx and K+ or Na+ efflux through specific ionic channels change
      the membrane potential and eventually lead to an increase in cAMP concentration
      in the cell, which constitutes the initiation signal for sperm motility in
      Salmonidae. 4. Media that are hyper- and hypo-osmotic relative to seminal fluid
      trigger sperm motility in marine and freshwater fishes, respectively. 5. The
      motility of fish spermatozoa is controlled through their sensitivity to
      osmolality and ion concentrations. This phenomenon is related to ionic channel
      activities in the membrane and governs the motility mechanisms of axonemes.

PMID- 16278090
TI  - Feline cholecystitis and acute neutrophilic cholangitis: clinical findings,
      bacterial isolates and response to treatment in six cases.
AB  - Clinicopathological findings from six cats with confirmed cholecystitis or acute
      neutrophilic cholangitis are presented. Historical findings included lethargy and
      anorexia or inappetence of up to five days duration. On physical examination all
      cats were pyrexic and four out of six were jaundiced and had cranial abdominal
      pain. Bile samples were obtained by cholecystocentesis at exploratory coeliotomy
      (two cases) or by percutaneous, ultrasound-guided cholecystocentesis (four
      cases). Gall bladder rupture and bile peritonitis occurred subsequent to
      ultrasound-guided cholecystocentesis in one case. The most common bacterial
      isolate was Escherichia coli (four cases); E coli was isolated alone in two
      cases, in combination with a Streptococcus species (one case) and in combination
      with a Clostridium species (one case). Streptococcus species alone was isolated
      from one case, as was Salmonella enterica serovar Typhimurium. The latter is the
      first reported case of Salmonella-associated cholecystitis in a cat. Concurrent
      pancreatic or intestinal disease was detected histologically in three cases. All
      cases were treated with antimicrobials based on in vitro susceptibility results.
      Treatment was successful in five cases. One cat with concurrent diffuse
      epitheliotropic intestinal lymphoma was euthanased. Percutaneous ultrasound
      guided cholecystocentesis is an effective, minimally-invasive technique enabling
      identification of bacterial isolates in cats with inflammatory hepatobiliary
      disease.

PMID- 16278091
TI  - Finite element modeling of multi-level cervical spinal segments (C3-C6) and
      biomechanical analysis of an elastomer-type prosthetic disc.
AB  - A three-dimensional finite element (FE) model for the multi-level lower cervical
      spinal segment C3-C6 has been developed using computed tomography (CT) data, and
      applied to study of the effects of the fusion and the artificial disc prosthesis
      on the biomechanical behavior of the lower cervical spine. The NURBS computer
      adided dedsig (CAD) data used in this study for modeling the vertebrae facilitate
      adding surface patch layouts for seamless attachment of the soft tissues, such as
      intervertebral discs onto the vertebrae. A FE model was completed by generating
      mesh out of this geometry. Its accuracy was validated by comparing with
      previously published experimental and numerical results for the flexion
      extension, axial rotation, and lateral bending moments. An implantation of an
      elastomer-type disc prosthesis or fused graft between C4-C5 vertebrae was
      considered in the FE model by modifying the intact disc. It is shown that the
      fusion reduced the mobility at its level by about 50-70% for the considered
      loading cases. It is numerically demonstrated that an elastomer with Young's
      modulus of 5.9 MPa for the artificial disc prosthesis well restores the
      biomechanical behavior of the intact spine.

PMID- 16278094
TI  - Erythermalgia: molecular basis for an inherited pain syndrome.
AB  - Inherited erythermalgia (also termed erythromelalgia) is characterized by severe
      pain in the limbs in response to mild thermal stimuli or exercise. Its molecular
      basis has, until recently, been enigmatic. Studies of families with autosomal
      dominant erythermalgia have now demonstrated mutations in sodium channel
      Na(v)1.7, which is selectively expressed within nociceptive dorsal root ganglion
      and sympathetic ganglion neurons. Shifts in activation and deactivation, and
      enhanced responses to small stimuli in mutant channels, decrease the threshold
      for single impulses and high-frequency trains of impulses in pain-sensing
      neurons. Erythermalgia, the first inherited painful neuropathy to be understood
      at a molecular level, is a model disease that could hold lessons for other
      painful conditions and for the development of rational, mechanism-based
      treatments for pain.

PMID- 16278095
TI  - Measuring patients' knowledge about heart failure.

PMID- 16278096
TI  - Training, assessment and competency in gynaecologic surgery.
AB  - The trainee gynaecologist requires specific teaching to achieve competency in
      gynaecological surgery. Basic skills such as knot tying and suturing should be
      acquired outside the operating theatre. They can be learned on simulations,
      including bench models, using synthetic materials, life-like models and animal
      tissue. Video training equipment is useful for the development of basic
      laparoscopic hand-eye coordination. Intermediate and advanced skills require
      simulations using more sophisticated bench models, live animals and virtual
      reality computerised systems. Structured teaching and assessment methods are
      essential. Surgical skills training models should be reliable and valid, and can
      be incorporated into an objective structured clinical examination, which could be
      used to assess individual development and allow progression through a training
      programme. Simulation training does translate into improved operative
      performance. Supervised operating experience on patients is crucial to training
      and should be assessed regularly using a global rating form with constructive
      feedback to facilitate improvement.

PMID- 16278097
TI  - The brain basis for episodic memory: insights from functional MRI, intracranial
      EEG, and patients with epilepsy.
AB  - This article reviews the contributions that functional magnetic resonance imaging
      (fMRI), intracranial electroencephalography (iEEG), and patient studies have made
      to our current understanding of how memory functions arise from the brain. First,
      we briefly discuss the current classification of different memory systems and
      their neuroanatomical correlates, focusing on episodic memory and evidence from
      lesion studies. We then survey both fMRI and iEEG studies of memory function. For
      each modality, we discuss its physiological basis, as well as point out key
      studies that have led to new insights regarding memory. Advantages and
      disadvantages of each brain mapping modality are addressed. Wherever appropriate,
      we point out implications these studies have for the treatment of patients with
      epilepsy. We conclude this review with further discussion regarding the potential
      for combining fMRI and iEEG techniques in future investigations of memory
      function.

PMID- 16278098
TI  - Nonconvulsive status epilepticus due to cefepime in a patient with normal renal
      function.
AB  - Status epilepticus and encephalopathy have been reported with use of
      cephalosporins in patients with renal failure. We here report the case of a 79
      year-old patient with normal renal function who developed subtle mental status
      changes during cefepime therapy for urinary tract infection. Emergent
      electroencephalography revealed evidence of nonconvulsive status epilepticus
      (NCSE), which responded initially to lorazepam. Later, the patient's NCSE
      gradually resolved only after cefepime was discontinued, with mental status
      returning to baseline as the electroencephalography changes resolved. It should
      be recognized that cefepime therapy can cause NCSE even in the presence of normal
      renal function. Measurement of serum concentrations and changes in dosing
      guidelines can probably prevent NCSE during cefepime therapy.

PMID- 16278099
TI  - Prolonged seizures and cellular injury: understanding the connection.
AB  - Status epilepticus (SE)-induced neuronal death is morphologically necrotic and is
      initiated by excessive glutamate release, which activates postsynaptic N-methyl-D
      aspartate (NMDA) receptors and triggers receptor-mediated calcium influx
      (excitotoxicity). This results in activation of intracellular proteases and
      neuronal nitric oxide synthase, with generation of free radicals, and damage to
      cellular membranes, structural proteins, and essential enzymes. Programmed cell
      death mechanisms, such as p53 activation, activation of cell death-promoting Bcl
      2 family members, and endonuclease-induced DNA laddering, occur in SE-induced
      neuronal death. Caspase-independent excitotoxic mechanisms, such as NMDA-induced
      calpain I activation, with activation and translocation of the cell death
      promoting Bcl-2 family member Bid from cytoplasm to mitochondria, and subsequent
      translocation of apoptosis-inducing factor and endonuclease G to nuclei (which
      cause large-scale and internucleosomal DNA cleavage, respectively), may be
      triggered by SE. Poly(ADP-ribose) polymerase-1 (PARP-1) activation and cysteinyl
      cathepsin and DNase II release from lysosomes may occur following SE as well, but
      these events await future investigation. In the future, rational combinations of
      central nervous system-penetrable neuroprotective agents, based on our knowledge
      of excitotoxic mechanisms, may be useful in refractory human SE.

PMID- 16278100
TI  - Comparison of the partial proteomes of the venoms of Brazilian spiders of the
      genus Phoneutria.
AB  - The proteomes of the venoms of the Brazilian wandering "armed" spiders Phoneutria
      nigriventer, Phoneutria reidyi, and Phoneutria keyserlingi, were compared using
      two-dimensional gel electrophoresis. The venom components were also fractionated
      using a combination of preparative reverse phase HPLC on Vydac C4, analytical RP
      HPLC on Vydac C8 and C18 and cation exchange FPLC on Resource S at pH 6.1 and
      4.7, or anion exchange HPLC on Synchropak AX-300 at pH 8.6. The amino acid
      sequences of the native and S-pyridyl-ethylated proteins and peptides derived
      from them by enzymatic digestion and chemical cleavages were determined using a
      Shimadzu PPSQ-21(A) automated protein sequencer, and by MS/MS collision induced
      dissociations. To date nearly 400 peptides and proteins (1.2-27 kDa) have been
      isolated in a pure state and, of these, more than 100 have had their complete or
      partial amino acid sequences determined. These sequences demonstrate, as might be
      expected, that the venoms of P. reidyi and P. keyserlingi (Family: Ctenidae) both
      contain a similar range of isoforms of the neurotoxins as those previously
      isolated from P. nigriventer which are active on neuronal ion (Ca(2+), Na(+) and
      K(+)) channels and NMDA-type glutamate receptors. In addition two new families of
      small (3-4 kDa) toxins, some larger protein (>10 kDa) components, and two serine
      proteinases of the venom of P. nigriventer are described. These enzymes may be
      responsible for some of the post-translational modification observed in some of
      the venom components.

PMID- 16278101
TI  - Correlation between pulmonary gas exchange and basal and nitroglycerin (GTN)
      induced exhaled nitric oxide (eNO) in patients undergoing cardiac surgery.
AB  - The relationship between eNO and events in the alveolar-capillary unit in acute
      lung injury remains to be established. Since endogenous eNO largely originates
      from the airway epithelium, but nitroglycerin (GTN)-induced eNO is due to
      microvascular/alveolar metabolism, we have proposed to use basal and GTN-induced
      eNO as metabolic markers of the airway--and microvascular/alveolar function,
      respectively. The current work investigates the relationship between basal and
      GTN-induced eNO and oxygenation parameters (PaO(2)/FiO(2) ratio) in patients
      undergoing cardiac surgery utilising cardiopulmonary bypass (CPB). Breath by
      breath eNO measurements were made in 10 patients before, and 1 and 3 h after CPB
      either under basal conditions or following intravenous administration of GTN (1,
      2 and 3 microg/kg). Basal eNO remained unchanged, whereas GTN-induced eNO was
      reduced following CPB. Also, there was a transient reduction in PaO(2)/FiO(2)
      ratio 1 h after CPB (32+/-4 vs. 44+/-3 kPa). A negative correlation was found
      between oxygenation and basal eNO by Pearson's correlation test and linear
      regression analysis suggesting that decreased oxygenation was associated with
      increased basal eNO. In contrast, a decrease in GTN-induced eNO positively
      correlated with reduced oxygenation index (R=0.533, p=0.002). These data suggest
      that differential relationships exist between basal and nitrovasodilator-induced
      eNO and oxygenation indices during subclinical lung injury in patients following
      CPB and that GTN-induced eNO evolution may reflect better microvascular events
      and injury.

PMID- 16278102
TI  - Recruitment to a trial of self-care skills training in long-term health
      conditions: analysis of the impact of patient attitudes and preferences.
AB  - The rise of evidence-based practice has highlighted the importance of effective
      recruitment to randomised controlled trials if studies are to be adequately
      powered and valid. However, there are also increasing concerns about patient
      preferences and choice within trials. The current authors are involved in a trial
      of a programme to provide self-care skills training for people with long-term
      health conditions (the 'Expert Patients Programme'), and during the design stage
      there were significant concerns about the impact of patient preferences on the
      feasibility and validity of the study, because recruitment required that patients
      risk randomisation to a waiting list control group. This paper first details the
      issues raised in this trial, and the methods used to attempt to overcome them.
      Data on recruitment rates, loss to follow up and patient decision making about
      participation are presented, which suggested that initial assumptions about the
      impact of patient preferences were incorrect. Key lessons concerning preferences
      in this patient population and related issues in trial administration are then
      discussed.

PMID- 16278103
TI  - Developmental expression of the high affinity choline transporter in cholinergic
      sympathetic neurons.
AB  - Choline uptake by the high affinity choline transporter (CHT) is the rate
      limiting step in acetylcholine synthesis. Induction of CHT is therefore a
      critical step in cholinergic differentiation, and we examined the developmental
      expression of CHT in cholinergic sympathetic neurons that innervate rodent sweat
      glands. During postnatal development the earliest sympathetic axons in the rear
      footpads are noradrenergic, containing intense tyrosine hydroxylase
      immunoreactivity and lacking CHT-immunoreactivity (CHT-IR). By postnatal day 7
      (P7) in mouse, and P10 in rat, weak CHT-IR appeared in axons associated with the
      sweat gland anlagen. CHT staining intensity increased during the following weeks
      in conjunction with plexus arborization and gland maturation. The pattern of CHT
      immunoreactivity (CHT-IR) in the sweat gland innervation was similar to staining
      for the vesicular acetylcholine transporter and vasoactive intestinal peptide.
      Immunoblots of tissue from sympathectomized rats confirmed that most of the CHT
      in footpad was contained in sympathetic neurons. Although CHT expression has been
      reported in noradrenergic sympathetic neurons of the superior cervical ganglion,
      these data indicate that in the sympathetic neurons projecting to sweat glands
      CHT is present at detectable levels only after association with the glands.

PMID- 16278104
TI  - Effect of nucleotide on interaction of the 567-578 segment of myosin heavy chain
      with actin.
AB  - To probe the effect of nucleotide on the formation of ionic contacts between
      actin and the 567-578 residue loop of the heavy chain of rabbit skeletal muscle
      myosin subfragment 1 (S1), the complexes between F-actin and proteolytic
      derivatives of S1 were submitted to chemical cross-linking with 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide. We have shown that in the absence of nucleotide
      both 45 kDa and 5 kDa tryptic derivatives of the central 50 kDa heavy chain
      fragment of S1 can be cross-linked to actin, whereas in the presence of
      MgADP.AlF4, only the 5 kDa fragment is involved in cross-linking reaction. By the
      identification of the N-terminal sequence of the 5-kDa fragment, we have found
      that trypsin splits the 50 kDa heavy chain fragment between Lys-572 and Gly-573,
      the residues located within the 567-578 loop. Using S1 preparations cleaved with
      elastase, we could show that the residue of 567-578 loop that can be cross-linked
      to actin in the presence of MgADP.AlF4 is Lys-574. The observed nucleotide
      dependent changes of the actin-subfragment 1 interface indicate that the 567-578
      residue loop of skeletal muscle myosin participates in the communication between
      the nucleotide and actin binding sites.

PMID- 16278105
TI  - Temporal changes in bone mass and mechanical properties in a murine model of
      tumor osteolysis.
AB  - Pathological fracture is a devastating complication of osteolytic bone
      metastases. The progression of osteolysis and its effect on bone fracture risk
      are poorly understood. The goal of this study was to determine the temporal
      changes in bone strength following tumor inoculation in a preclinical model of
      tumor osteolysis. In addition, a predictive model was developed between non
      invasive radiographic measures and bone strength. The right femora of female nude
      mice were injected with breast cancer cells; the left limb served as a sham
      operated control. Radiographs and DEXA scans were obtained at the time of surgery
      and at 3, 6, and 9 weeks. Groups of mice were euthanized at each time point for
      mechanical assessment. Micro-CT analysis was performed on a sub-set of mice with
      advanced state disease to quantify bone loss. Radiographs documented an increase
      in tumor osteolysis over time, with 58% of the mice showing signs of osteolysis
      at 3 weeks, 75% at 6 weeks, and 81% at 9 weeks. BMD measurements revealed a 21.6%
      increase from baseline in the controls whereas tumor-injected femora failed to
      increase in BMD over the same time course. Tumor-bearing limbs exhibited
      statistically significant decreases in torque at failure (86%), energy to failure
      (88%), and initial stiffness (94%) compared to the controls. Both lysis scores
      and BMD measurements proved to be modest predictors of mechanical strength,
      accounting for approximately 73% and 41% of variation in torque at failure,
      respectively. Micro-CT analysis revealed decreases in both total bone volume in
      the distal femur (31%) and metaphyseal fractional trabecular bone (89%). We have
      shown that non-invasive radiographic techniques provide a useful tool for
      monitoring the progression of tumor osteolysis and for predicting the mechanical
      strength of tumor-bearing bones in this model. By integrating non-invasive
      measures of tumor osteolysis and fracture risk, we have validated a clinically
      relevant platform for evaluating new therapeutic approaches for preserving and/or
      restoring bone affected by metastatic disease.

PMID- 16278106
TI  - Feature extraction from Doppler ultrasound signals for automated diagnostic
      systems.
AB  - This paper presented the assessment of feature extraction methods used in
      automated diagnosis of arterial diseases. Since classification is more accurate
      when the pattern is simplified through representation by important features,
      feature extraction and selection play an important role in classifying systems
      such as neural networks. Different feature extraction methods were used to obtain
      feature vectors from ophthalmic and internal carotid arterial Doppler signals. In
      addition to this, the problem of selecting relevant features among the features
      available for the purpose of classification of Doppler signals was dealt with.
      Multilayer perceptron neural networks (MLPNNs) with different inputs (feature
      vectors) were used for diagnosis of ophthalmic and internal carotid arterial
      diseases. The assessment of feature extraction methods was performed by taking
      into consideration of performances of the MLPNNs. The performances of the MLPNNs
      were evaluated by the convergence rates (number of training epochs) and the total
      classification accuracies. Finally, some conclusions were drawn concerning the
      efficiency of discrete wavelet transform as a feature extraction method used for
      the diagnosis of ophthalmic and internal carotid arterial diseases.

PMID- 16278107
TI  - Telematics enabled virtual simulation system for radiation treatment planning.
AB  - In this paper, GALENOS, a Telematics Enabled Virtual Simulation System for
      Radiation Treatment Planning (RTP) is described. The design architecture of
      GALENOS is in accordance with the dual aim of virtual simulation of RTP, i.e. to
      allow (a) delineation of target volume and critical organs, and (b) placement of
      irradiation fields. An important feature of GALENOS is the possibility for on
      line tele-collaboration between health care professionals under a secure
      framework. The advantages of GALENOS include elimination of patient transfers
      between departments and health care institutions as well as availability of
      patient data at sites different than those of his/her physical presence.

PMID- 16278108
TI  - The usability of videophones for seniors and hospice providers: a brief report of
      two studies.
AB  - This article uses a human factors evaluation framework to assess the usability of
      commercially available videophone technology. One study focuses on minimally
      functionally impaired seniors living in an assisted living facility. The second
      study focuses on usability for hospice staff. Seniors found the technology easy
      to use and were willing to accept the equipment in their homes, especially if
      requested by a healthcare provider. Administrators and hospice care providers
      also reported that the videophones were easy to use and would be of benefit to
      the patients they care for. The results indicate that videophones are a promising
      intervention with identifiable limitations.

PMID- 16278109
TI  - 3-D quantification and visualization of vascular structures from confocal
      microscopic images using skeletonization and voxel-coding.
AB  - This paper presents an image processing approach for information extraction from
      three-dimensional (3-D) images of vasculature. It extracts quantitative
      information such as skeleton, length, diameter, and vessel-to-tissue ratio for
      different vessels as well as their branches. Furthermore, it generates 3-D
      visualization of vessels based on desired anatomical characteristics such as
      vessel diameter or 3-D connectivity. Steps of the proposed approach are: (1) pre
      processing, (2) distance mappings, (3) branch labeling, (4) quantification, and
      (5) visualization. We have tested and evaluated the proposed algorithms using
      simulated images of multi-branch vessels and real confocal microscopic images of
      the vessels in rat brains. Experimental results illustrate performance of the
      methods and usefulness of the results for medical image analysis applications.

PMID- 16278110
TI  - Adaptive signal enhancement of somatosensory evoked potential for spinal cord
      compression detection: an experimental study.
AB  - The objective of this study was to assess the efficacy of adaptive signal
      enhancement (ASE) as a means of indicating intraoperative spinal cord
      impingement. ASE technique was used to determine the changes in the somatosensory
      evoked potential (SEP) elicited from eighteen rats with varying levels of spinal
      cord compression. ASE technique was found to be able to effectively extract SEP
      signals for the detection of spinal cord injury. Furthermore, while the
      traditional ensemble averaging (EA) technique requires more than 500 trials for
      meaningful signal processing in severe noisy SEP recordings, the ASE method
      required only 50 trials to provide similar information. Because of its fast and
      reliable SEP detection, the ASE method is ideal for spinal cord monitoring in the
      clinical setting.

PMID- 16278111
TI  - Error estimation of geometrical data obtained by histomorphometry of oblique
      vessel sections: a computer model study.
AB  - The errors of radius and wall thickness of a single vessel due to oblique
      sectioning in histomorphometry are expressed as a function of the circular shape
      factor (CSF) of the section's lumen, assuming cylindrical geometry and the
      absence of tissue deformation. Using computer model trees generated by
      constrained constructive optimization, mean errors are estimated for an ensemble
      of vessel segments. A geometrical exclusion criterion for segments cut too
      obliquely is defined on the basis of a CSF-cutoff value. It is shown that CSF
      values ranging from 0.95 to 0.9 are reasonable choices for a cutoff and lead to
      mean errors of the same order of magnitude (9.6% [9.3%] to 15.4% [14.8%] for the
      radius [wall thickness]) as errors due to histological tissue processing.

PMID- 16278114
TI  - Acute coronary syndromes: risk stratification and initial management.
AB  - For patients who have acute coronary syndromes (ACS), risk stratification is key
      to initiating appropriate treatment. For ST-segment elevation MI, immediate
      reperfusion therapy is needed, and thus rapid identification of ST elevation on
      the ECG is critical. Then, having a standardized protocol for rapid treatment-
      with either primary percutaneous coronary intervention or thrombolysis - is
      critical. For unstable angina/non-ST elevation ACS, after first identifying the
      patients who have a higher likelihood of actually having an ACS (as opposed to
      noncardiac chest pain) stratification to high versus lower risk is needed to
      choose appropriate therapies. Thus, it is important for risk stratification to be
      a central part of all management of patients who have ACS.

PMID- 16278115
TI  - Chest pain unit concept: rationale and diagnostic strategies.
AB  - Each year in the United States, over 8 million patients present to the emergency
      department(ED) with complaints of chest discomfort or other symptoms consistent
      with possible acute coronary syndrome (ACS). While over half of these patients
      are typically admitted for further diagnostic evaluation, fewer than 20% are
      diagnosed with ACS. With hospital beds and inpatient resources scarce, these
      admissions can be avoided by evaluating low- to moderate-risk patients in chest
      pain units. This large, undifferentiated patient population represents a
      potential high-risk group for emergency physicians requiring a systematic
      approach and specific ED resources. This evaluation is required to appropriately
      determine if a patient is safe to be discharged home with outpatient follow-up
      versus requiring admission to the hospital for monitoring and further testing.

PMID- 16278116
TI  - Acute coronary syndromes in the emergency department: diagnostic characteristics,
      tests, and challenges.
AB  - Failure to diagnose patients who have acute coronary syndromes (ACSs)-either
      acute myocardial infarction (AMI) or unstable angina pectoris (UAP)-who present
      to the emergency department (ED) remains a serious public health issue. Better
      understanding of the pathophysiology of coronary artery disease has allowed the
      adoption of a unifying hypothesis for the cause of ACSs: the conversion of a
      stable atherosclerotic lesion to a plaque rupture with thrombosis. Thus,
      physicians have come to appreciate UAP and AMI as parts of a continuum of ACSs.
      This article reviews the state of the art regarding the diagnosis of ACSs in the
      emergency setting and suggests reasons why missed diagnosis continues to occur,
      albeit infrequently.

PMID- 16278117
TI  - Use of biomarkers in the emergency department and chest pain unit.
AB  - The use of biomarkers of cardiac injury in the emergency department (ED) and
      observation unit settings has several nuances that are different and, therefore,
      worthy of its own set of use guidelines. The markers that are used, however, are
      the same. The primary marker of choice continues to be cardiac troponin (Tn).
      Other markers that have been used because of the need in the ED for rapid triage
      have been myoglobin and fatty acid binding protein. In addition, some centers
      still prefer less sensitive and less specific markers such as creatine kinase
      myocardial band (CK-MB). More recently, a push has occurred to develop markers of
      ischemia, such as ischemia modified albumin (IMA),to determine which patients
      have ischemia, even in the absence of cardiac injury. As troponin assays become
      more sensitive and method for use becomes better understood, the use of these
      other markers are being relegated to lesser and lesser roles. Markers of ischemia
      are useful, but at present, despite some enthusiasm, are not ready for routine
      use. Before describing the recommendations for clinical use of biomarkers in the
      ED, a basic understanding of some of the science and measurement issues related
      to these analytes is helpful.

PMID- 16278118
TI  - Point-of-Care Testing and Cardiac Biomarkers: The Standard of Care and Vision for
      Chest Pain Centers.
AB  - Point-of-care testing (POCT) is defined as testing at or near the site of patient
      care. POCTdecreases therapeutic turnaround time (TTAT), increases clinical
      efficiency, and improves medical and economic outcomes. TTAT represents the time
      from test ordering to patient treatment. POC technologies have become ubiquitous
      in the United States, and, therefore,so has the potential for speed, convenience,
      and satisfaction, strong advantages for physicians, nurses, and patients in chest
      pain centers. POCT is applied most beneficially through the collaborative
      teamwork of clinicians and laboratorians who use integrative strategies,
      performance maps, clinical algorithms, and care paths (critical pathways). For
      example, clinical investigators have shown that on-site integration of testing
      for cardiac injury markers (myoglobin, creatinine kinase myocardial band
      [CKMB],and cardiac troponin I [cTnI]) in accelerated diagnostic algorithms
      produces effective screening, less hospitalization, and substantial savings.
      Chest pain centers, which now total over 150 accredited in the United States,
      incorporate similar types of protocol-driven performance enhancements. This
      optimization allows chest pain centers to improve patient evaluation, treatment,
      survival, and discharge. This article focuses on cardiac biomarker POCT for chest
      pain centers and emergency medicine.

PMID- 16278119
TI  - Markers of cardiac ischemia and inflammation.
AB  - Because biomarkers of myocardial necrosis only become positive in the setting of
      myocardial necrosis and disruption of cellular integrity, the diagnosis of
      myocardial infarction can only be made in retrospect. Ideally, one would like to
      identify patients at risk for complications before myocardial necrosis occurs.
      Insights into the pathophysiology of atherothrombosis have allowed development of
      novel markers to detect not only early ischemia without myocyte death but also
      early indicators of coronary inflammation inpatients who have preclinical
      atherosclerosis.

PMID- 16278120
TI  - Exercise testing in chest pain units: rationale, implementation, and results.
AB  - Chest pain units are now established centers for assessment of low-risk patients
      presenting to the emergency department with symptoms suggestive of acute coronary
      syndrome. Accelerated diagnostic protocols, of which treadmill testing is a key
      component, have been developed within these units for efficient evaluation of
      these patients. Studies of the last decade have established the utility of early
      exercise testing,which has been safe, accurate, and cost-effective in this
      setting. Specific diagnostic protocols vary, but most require 6 to 12 hours of
      observation by serial electrocardiography and cardiac injury markers to exclude
      infarction and high-risk unstable angina before proceeding to exercise testing.
      However, in the chest pain unit at UC Davis Medical Center,the approach includes
      "immediate" treadmill testing without a traditional process to rule out
      myocardial infarction. Extensive experience has validated this approach in a
      large, heterogeneous population. The optimal strategy for evaluating low-risk
      patients presenting to the emergency department with chest pain will continue to
      evolve based on current research and the development of new methods.

PMID- 16278121
TI  - Imaging in the evaluation of the patient with suspected acute coronary syndrome.
AB  - Over the last decade, major advances have been made in the treatment of acute
      coronary syndromes (ACSs). However, effective implementation of these treatments
      requires timely and accurate identification of the high-risk patient among all
      those presenting to the emergency department (ED) with symptoms suggestive of
      ACS. The opportunity for improving outcomes is time-dependent, so that early
      identification of the patient who has true ACS is essential. This necessity
      further increases the need for rapid triage tools, especially in the current
      setting of ED and hospital overcrowding that has become the norm in large urban
      centers.

PMID- 16278122
TI  - Echocardiography in the evaluation of patients in chest pain units.
AB  - Using percutaneous angioplasty to induce the ischemic cascade in the cardiac
      catheterization laboratory, echocardiographic wall motion abnormalities have been
      documented to precede electrocardiographic abnormalities and angina. Therefore,
      detection of cardiac wall motion abnormalities is potentially more sensitive than
      the history, physical examination, and ECG for identification of myocardial
      ischemia. Echocardiography is highly reliable for assessing cardiac wall motion
      and, thus, it has been used for diagnosis and risk assessment in patients
      presenting to the emergency department (ED) with symptoms suggestive of
      myocardial ischemia. In patients who have acute ST-elevation myocardial
      infarction (MI), echocardiography is comparable to invasive left ventriculography
      for detecting wall motion abnormalities. However, the usefulness of
      echocardiography in the low-risk population that has chest pain of uncertain
      origin and a nondiagnostic initial presentation is less well established.

PMID- 16278123
TI  - Newer imaging methods for triaging patients presenting to the emergency
      department with chest pain.
AB  - The usefulness of electron beam CT (EBCT) for the risk stratification of patients
      in the emergency department (ED) who have possible acute coronary syndrome has
      been evaluated in three small studies. The results of these studies are
      promising, as patients who have no coronary calcium detected by EBCT essentially
      had no adverse cardiac events. Although the negative predictive value of EBCT was
      excellent, the limited positive predictive value that would lead to further
      diagnostic testing makes this strategy less attractivei f applied to a broad
      population. Further larger studies may help define which patients in the ED who
      have chest pain and nondiagnostic ECGs can be effectively evaluated by EBCT.
      Recent advances in noninvasive coronary angiography by multislice computed
      tomography are of considerable interest in the ED evaluation of patients with
      undefined chest pain, but the utility of this method in this setting awaits
      clinical studies.

PMID- 16278124
TI  - Chest pain units: management of special populations.
AB  - Chest pain units provide an important alternative to traditional hospital
      admission for patients who present to the emergency department with symptoms
      compatible with acute coronary syndrome and a normal or inconclusive initial
      evaluation. Although patient subgroups such as women, diabetics, those with
      established coronary artery disease,and those with symptoms related to stimulant
      use present unique challenges,management in a chest pain unit appears to be
      appropriate in these populations. Judicious application of accelerated diagnostic
      protocols and current testing methods can promote safe, accurate, and cost
      effective risk stratification of special populations to identify patients who can
      be safely discharged and patients who require hospital admission for further
      evaluation.

PMID- 16278125
TI  - Management of the patient with chest pain and a normal coronary angiogram.

PMID- 16278126
TI  - Using the emergency department clinical decision unit for acute decompensated
      heart failure.
AB  - Acute decompensated heart failure (ADHF) is a complex disease of epidemic
      proportions. In the United States, it accounts for more than 1 million
      hospitalizations annually,and heart failure represents the single greatest cost
      to the Centers for Medicaid and Medicare Studies. Half of the annual costs are
      estimated to be the result of hospitalization. Compared with other pathology,
      heart failure has a very high hospitalization rate, with 80% of emergency
      department ADHF patients being admitted. This high rate has resulted from the
      lack of successful management predictors available to the emergency physician and
      the lack of any disposition option other than hospitalization for the ADHF
      patient. The emergency department observation unit offers an alternative to
      hospitalization for patients with ADHF. Validated protocols have demonstrated
      that in ADHF, intensive short-term therapeutic, diagnostic, and educational
      protocols result in a marked improvement in hospitalization rates, while at the
      same time decreasing costs. New risk stratification data can aid in the
      identification of the appropriate candidate. The observation unit now represents
      a nonhospitalization disposition option for patients presenting to the emergency
      department with ADHF.viii CO

PMID- 16278127
TI  - Cost effectiveness of chest pain units.
AB  - Health care facilities face many challenges in their attempts to provide cost
      effective care without sacrificing quality. One key factor in producing quality
      outcomes while maintaining economic profitability is the establishment of a cost
      effective outpatient care environment. Chest Pain Units (CPUs) have evolved to
      provide a streamlined approach to acute cardiac care that emphasizes optimal
      efficiency initiated at the point of entry. The Centers for Medicare and Medicaid
      Services have structured new reimbursement approaches designed to shift care from
      the inpatient setting and "reward" efficient and appropriate care delivered in
      the outpatient arena. These new reimbursement strategies have transformed the CPU
      into an economically viable entity for the acute care facility and also have
      afforded opportunities to enhance the quality of care delivered to the acute
      cardiac patient.

PMID- 16278128
TI  - Medical error prevention in ED triage for ACS: use of cardiac care decision
      support and quality improvement feedback.
AB  - Medical errors in the care of patients who present with acute coronary syndrome
      (ACS)include errors in emergency department (ED) triage, such as the decision to
      send home a patient who presents with ACS or to hospitalize a patient who does
      not have ACS to the cardiac care unit (CCU), and errors in treatment, such as the
      failure to promptly use reperfusion therapy for patients who present with ST
      elevation acute myocardial infarction(AMI). ECG-based acute cardiac ischemia time
      insensitive predictive instrument(ACI-TIPI) and thrombolytic predictive
      instruments (TPIs), with a linked TIPI information system (TIPI-IS), provide real
      time, concurrent, and retrospective decision support tools and feedback for the
      prevention of medical errors in the care of patients who present with ACS. In
      real-time, ACI-TIPI probabilities printed on the ECG header for the ED physician,
      provide an additional piece of information for triage decision making, and the
      ACI-TIPI Risk Management form reduces liability risk by prompting consideration
      and documentation of key clinical factors in the diagnosis of ACI. Also in real
      time, the TPI increases overall coronary reperfusion therapy use. Concurrent
      flagging by TIPI-IS uses electronically acquired ECG and hospital data to provide
      concurrent alerts about potential misdiagnosis or mis-triage of patients with
      ACS. Retrospectively TIPI-IS-based feedback reports allow performance
      improvement. These examples of information technology tools integrated into ECG
      equipment already used in hospitals to deliver patient care demonstrate the
      potential to adapt other existing equipment or other patient care activities to
      enhance patient safety and error reduction.

PMID- 16278131
TI  - Sedation and the technical performance of colonoscopy.
AB  - The use of sedation for routine endoscopic procedures, including colonoscopy,
      varies widely across cultures. This variation in sedation practice is greater
      than any other culturally based variation in the technical performance of
      endoscopy. This article sequentially reviews the technical performance of
      colonoscopy in patients who undergo unsedated colonoscopy, sedation with
      narcotics and benzodiazepines, and deep sedation with propofol. For each of these
      approaches to colonoscopy, the advantages and disadvantages also are listed and
      discussed.

PMID- 16278132
TI  - Aids to insertion: magnetic imaging, variable stiffness, and overtubes.
AB  - Inserting the colonoscope quickly and safely without undue patient discomfort is
      the primary aim of the colonoscopist. The inherently mobile, flexible and
      unpredictable nature of the colon means that looping occurs frequently during
      insertion and the colonoscopist must constantly strive to keep the instrument
      straight whilst at the same time advancing the tip towards the caecum.
      Colonoscopists have struggled with insertion for many years but recent
      developments described in this chapter have the potential to make insertion
      easier and more predictable.

PMID- 16278133
TI  - Practical uses of chromoendoscopy and magnification at colonoscopy.
AB  - New technologies in the form of high-magnification or zoom colonoscopy
      complemented by chromoscopic agents permits early detection of neoplastic
      colorectal lesions, particularly flat and depressed types. Establishing
      suitability for endoscopic resection or surgical excision can be enhanced using
      these techniques. Chromoscopic colonoscopy may play an important role in the
      routine endoscopic colorectal cancer surveillance programs in patients assuming a
      high risk of colorectal neoplasia. This article summarizes recent data regarding
      the prevalence and histopathologic characteristics of flat and depressed
      colorectal lesion in Western cohorts and describes how their detection and
      management can be improved by chromoscopy and magnification technology. The
      techniques required for chromoscopic colonoscopy and magnification imaging are
      outlined along with a review of the literature on these subjects.

PMID- 16278134
TI  - New imaging techniques at colonoscopy: tissue spectroscopy and narrow band
      imaging.
AB  - Although colonoscopy has undergone impressive development in recent decades,
      there remains a need for better endoscopic visualization in specific
      circumstances (eg, dysplasia screening in ulcerative colitis and detection of
      flat colorectal lesions). Many techniques are under investigation; this article
      discusses different forms of spectroscopy and narrow band imaging. Ideal
      colonoscopy should have high diagnostic accuracy and the ability to screen large
      mucosal areas. The most successful clinical method probably will be a combination
      of techniques, providing wide-area surveillance (such as fluorescence endoscopy
      or immunoscopy) and point detection methods, such as narrow band imaging or
      confocal microendoscopy, that can be used to identify the lesion further.

PMID- 16278135
TI  - Confocal laser endomicroscopy.
AB  - A miniaturized confocal microscope was developed that could be integrated in the
      distal tip of a conventional colonoscope. With this technique, denoted confocal
      endomicroscopy, subsurface analysis of the gut mucosa and in-vivo histology
      during ongoing endoscopy are possible in full resolution by point scanning laser
      analysis. The diagnostic spectrum of confocal endomicroscopy is expanding from
      screening and surveillance for colorectal cancer to Barrett's esophagus,
      Helicobacter pylori-associated gastritis, and gastric cancer. The new detailed
      images seen with confocal laser endomicroscopy allow a unique look on cellular
      structures at and below the surface of the gut. This review describes the optical
      and diagnostic possibilities of confocal laser endomicroscopy.

PMID- 16278136
TI  - Advanced polypectomy.
AB  - Advanced polypectomy includes the approach to large polyps, polyps that are
      difficult to access, and polyps that require special maneuvers for removal.
      Sessile polyps are considered difficult to remove, the larger diameters falling
      into the "very difficult" category, requiring advanced polypectomy techniques.
      Some pedunculated polyps may require advanced techniques. Most polyps in the
      colon are sessile, and many of these are located in the right colon, from the
      hepatic flexure to the cecal caput. Pedunculated polyps, with a pedicle of pulled
      out mucosa and submucosa caused by the constant action of peristalsis in the
      colon's attempt to evacuate the polyp, usually are located in the sigmoid colon.

PMID- 16278137
TI  - Colonic stenting: technique, technology, and outcomes for malignant and benign
      disease.
AB  - Self-expandable metal stents (SEMS) have gained acceptance for use in the
      gastrointestinal tract to relieve malignant lumenal obstruction. In the colon,
      SEMS are used to avoid permanent or temporary colostomy during palliation and as
      a bridge to surgery for left-sided colonic obstruction. Limited data exist on
      their use for benign disease. This article reviews the latest in stent technology
      and the outcomes after their placement for benign and malignant disease.

PMID- 16278138
TI  - Virtual colonoscopy: current status and future directions.
AB  - Virtual colonoscopy (CT colonography) is a technique whereby CT images of the
      cleansed and distended colon are acquired, ostensibly for detecting colonic
      neoplasia, although also providing additional diagnostic information from
      extracolonic organs. This article examines the current status of virtual
      colonoscopy, reviewing the technical parameters, performance characteristics, and
      issues surrounding implementation in routine clinical practice. Future directions
      for virtual colonoscopy are explored, including advances toward prepless
      examinations and automated interpretation.

PMID- 16278139
TI  - Virtual colonoscopy by MRI: state-of-the-art and future directions.
AB  - MR colonography has been shown to be an appropriate diagnostic tool for the
      detection of colorectal lesions. The technique is based on the acquisition of T1
      weighted sequences after the administration of water enema and the intravenous
      administration of paramagnetic contrast. This article describes the technical
      requirements for MR colonoscopy and the procedures of data acquisition and image
      interpretation. The advantages and drawbacks of MR colonoscopy also are outlined.

PMID- 16278140
TI  - Colonoscopy training--new approaches, old problems.
AB  - Colonoscopy traditionally has been taught using the apprenticeship approach.
      Assessment of competence has been, at best, informal and based largely on the
      number of procedures trainees have performed. The advent of colorectal cancer
      screening has demanded formalization of training and assessment using structured
      teaching and state-of-the-art training tools, such as computer simulation. New
      generation approaches and technology have the ability to raise the standard of
      coloscopy provided by competent practitioners.

PMID- 16278141
TI  - The nurse colonoscopist--training and quality assurance.
AB  - Specialist trained nurses have been performing flexible sigmoidoscopy as part of
      their nursing role since the 1970s in the United States. As nurses have shown
      their efficacy and effectiveness in performing flexible sigmoidoscopy, this new
      nursing role has been adopted more globally in the United Kingdom and other
      European countries.

PMID- 16278142
TI  - Colonoscopy: new designs for the future.
AB  - The main purpose of this article is to outline various devices of varying
      practicality that have been described that might allow the examination of the
      colon by other means. These methods include tip propulsion by various methods,
      robotics, wireless endoscopy, free capsule endoscopy, specialized overtube use,
      and toposcopy.

PMID- 16278143
TI  - Tipping the balance towards tolerance: the basis for therapeutic immune
      modulation by gold?
AB  - Gold salts have long been used in the treatment of rheumatoid arthritis. However,
      the basis for their therapeutic immune-modulating properties has never been
      satisfactorily explained. Furthermore, treatments are often marred by the
      development of adverse immune reactions such as hypersensitivity and even
      exacerbation of autoimmunity. We would like to propose a hypothesis to explain
      the basis for both the beneficial and adverse immune-modulating effects of gold
      in the treatment of rheumatoid arthritis. If accepted, this hypothesis will allow
      for the development of safer and more effective treatments with gold salts. The
      principle underlying this hypothesis also has broader implications for how immune
      hypersensitivity and tolerance are perceived.

PMID- 16278144
TI  - Age-related loss of bone marrow pre-B- and immature B-lymphocytes in the
      autoimmune-prone flaky skin mutant mice.
AB  - Defective B-lymphopoiesis has been associated with development of auto-antibodies
      and auto-immunity in a number of autoimmune-prone strains of mice. The flaky skin
      (fsn) mutation results in development of chronic inflammation and auto-immunity.
      Associated with the development of auto-immunity is the hyperactivation of B
      lymphocytes and production of auto-antibodies. We, therefore, undertook a
      detailed examination of B-lineage precursors in the bone marrow of fsn/fsn mice.
      We observed a rapid age-related loss of the pre-B and immature B cells. It was
      also noted that an accumulation of early precursor populations occurs coincident
      with the loss of Fr.D and Fr.E bone marrow B cell populations indicating a
      developmental block or accumulation of pro-B cells in 7 and 10 week old fsn/fsn
      mice. Our data suggests changes in the fsn/fsn bone-marrow microenvironment that
      results in senescence of B cell development.

PMID- 16278145
TI  - A longitudinal study of the relationship between galactosylation degree of IgG
      and rheumatoid factor titer and avidity during long-term immunization of rabbits
      with BSA.
AB  - Although IgG with reduced content of galactose has been implicated as important
      in the autoimmune rheumatoid factor (RF) response in rheumatoid arthritis (RA),
      relatively little is known about the temporal relationship between RF and the
      degree of galactosylation of IgG in vivo. We established an experimental model
      for studying the dynamic association between changes in the relative extent of
      galactosylation of IgG antigen(s) and the main parameters of RF activity, such as
      the titer, specificity and functional affinity/avidity. Rabbits hyperimmunized
      with BSA were used for examining the influence of long-term antigenic stimulation
      on the galactosylation status of IgG and rheumatoid factor production. The
      results showed that the galactosylation profile of IgG varied during the humoral
      anti-BSA response in rabbits and that the accompanying RF response fluctuated in
      titer and binding avidity for differently galactosylated IgG. The immune
      complexes (IC) were found to be composed of differently galactosylated IgG
      differing in capacity to inhibit the agglutination activity of RF. Moreover, the
      ability of circulating RF to react avidly with rather small IC was associated
      with a lower content of galactose in complexed IgG. The results suggest that a
      certain dynamic relationship exists between the oligosaccharide moiety of IgG and
      the titer and avidity of RF during the normal anti-BSA response of rabbits.

PMID- 16278146
TI  - Antibodies to glutamate receptor subtype 3 (GluR3) are found in some patients
      suffering from epilepsy as the main disease, but not in patients whose epilepsy
      accompanies antiphospholipid syndrome or Sneddon's syndrome.
AB  - Autoantibodies (Ab's) to the "B" peptide (amino acids 372-395) of glutamate/AMPA
      receptor subtype 3 (GluR3) are found in serum and cerebrospinal fluid of some
      patients with different types of epilepsy. Since such anti-GluR3B Ab's can
      activate and/or kill neurons in vitro and in vivo, they may contribute to
      epilepsy. To investigate whether anti-GluR3B Ab's may also be relevant to
      epilepsy when it accompanies some autoimmune-diseases, we tested for these Ab's
      in patients suffering from epilepsy that accompanies anti-phospholipid syndrome
      (APS) or Sneddon's syndrome (SNS), both being autoimmune-diseases with frequent
      neurological complications. We tested 77 pediatric patients whose epilepsy is
      their main disease; 31 adult patients whose epilepsy accompanies APS (primary or
      SLE-associated) or SNS; 45 epilepsy-free APS and SNS patients; and 90 healthy
      controls. Compared to the controls, significantly elevated anti-GluR3B Ab's were
      found in 22/77 (29%) patients whose epilepsy is their main disease, but in none
      of the patients whose seizures accompany APS or SNS. Yet, all the APS and SNS
      patients harbored the characteristic anti-phospholipid Ab's (aPL), directed
      against cardiolipin and beta2-glycoprotein I, and had lupus anti-coagulant. Thus,
      anti-GluR3B Ab's are not crossreactive with aPL, and not produced as a non
      specific consequence of seizures on the one hand, or autoimmune-diseases on the
      other. Taken together with new findings accumulated recently in our lab, we
      suggest that anti-GluR3B Ab's are produced primarily in the periphery due to
      specific/non-specific "irritation" of the immune system, and that once they reach
      the brain via a leaky blood-brain barrier they may cause neuronal/glial damage
      and facilitate the outburst of epilepsy and additional neurological
      abnormalities. In contrast, the presence of anti-GluR3B Ab's does not seem to
      increase the probability of developing APS, SNS or the seizures that often
      accompany these autoimmune-diseases. These findings may have important diagnostic
      and therapeutic implications.

PMID- 16278147
TI  - Antibodies against annexin A5: detection pitfalls and clinical associations.
AB  - Antiphospholipid syndrome (APS) has been defined as a clinical and laboratory
      entity. Laboratory criteria include the presence of anticardiolipin antibodies
      (aCL) and/or lupus anticoagulant (LA), collectively termed as antiphospholipid
      antibodies (aPL). However, there has been a rising interest in antibodies against
      so-called protein cofactors, particularly in beta(2)-glycoprotein I. In the early
      90s, annexins were considered as target antigens for aPL, but at present the
      exact role of antibodies against annexins (aANX) remains puzzling. This review is
      concerned with annexin V or annexin A5 (ANXA5), a widespread member of the
      annexin family, and antibodies directed towards it. We have endeavoured to
      summarise essential information about the detection of anti-annexin V antibodies
      (aANXA5) and their clinical relevance. This review has also brought together some
      relevant published data concerning the structure, physiological role and
      therapeutic potential of ANXA5.

PMID- 16278148
TI  - Binding of circulating SLE autoantibodies to oxygen free radical damaged
      chromatin.
AB  - Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease
      characterized by various immunologic disorders, including production of
      autoantibodies, formation of immune complexes, decreased serum complement levels,
      and lymphocytopenia. One of the hallmarks of this disease is the loss of
      tolerance to nuclear antigens. The dominant presence of antibodies against the
      exposed conformational epitopes on chromatin strongly suggests that the
      pathogenic immune response in lupus is driven by chromatin. In the present study,
      the binding of SLE autoantibodies with native chromatin and oxygen free radical
      damaged chromatin was studied. As assessed by direct binding and inhibition
      ELISA, circulating SLE autoantibodies exhibited a high degree of specificity
      towards the reactive oxygen species (ROS)-modified chromatin in comparison to
      native chromatin and this binding specificity was reiterated visually by gel
      retardation assay. The data suggested possible role of modified chromatin in the
      induction of SLE autoantibodies and higher recognition of oxidatively damaged
      chromatin by antibodies in sera of SLE patients. It is indicated that free
      radical modified chromatin or nucleosomes might be the antigen for the production
      of circulating autoantibodies in SLE.

PMID- 16278149
TI  - Heterogeneity of vitamin D receptor gene association with celiac disease and type
      1 diabetes mellitus.
AB  - OBJECTIVE: Vitamin D has been shown to exert multiple immunomodulatory effects
      and is known to suppress T-cell activation by binding to the vitamin D receptor
      (VDR). To determine whether VDR gene polymorphisms are related to the
      susceptibility to celiac disease, we investigated its implication as a candidate
      gene in the Basque population. Because celiac disease and type 1 diabetes share
      common susceptibility loci, we also analyzed families with type 1 diabetes
      mellitus. METHODS: A total of 37 families with celiac disease and 64 type 1
      diabetic families of Basque origin with at least one affected offspring were
      genotyped for four VDR restriction-site polymorphisms (Fok I, Bsm I, Apa I and
      Taq I). The AFBAC approach was used to test for association. RESULTS: Comparison
      of VDR genotypes of the patients with those of 88 healthy individuals identified
      "ff" as a risk genotype for celiac disease [p = 0.01; OR = 3.45 (1.12-10.79)]. On
      the other hand, a significantly higher frequency of haplotype "fBAt" was observed
      in the type 1 diabetic group [p(c) = 0.02; OR = 4.4 (1.5-15.3)]. CONCLUSION: Our
      findings suggest that polymorphisms within the vitamin D receptor gene are
      markers of susceptibility to or protection from autoimmune diseases, although, at
      least in the Basque population, association of VDR variants with celiac disease
      and type 1 diabetes seems to be heterogeneous.

PMID- 16278150
TI  - Autoantibodies to survivin in patients with chronic hepatitis and hepatocellular
      carcinoma.
AB  - OBJECTIVES: Autoantibodies to tumor-associated antigens including survivin have
      been detected in sera from patients with hepatocellular carcinoma (HCC). However,
      little is known about autoantibody responses to tumor-associated antigens in
      patients with chronic hepatitis, which strongly predisposes to development of
      HCC. METHODS: We subjected sera from 57 patients with chronic hepatitis and 29
      patients with HCC to an enzyme-linked immunosorbent assay (ELISA) using a full
      length recombinant survivin protein. A cutoff value for positivity was determined
      as the mean absorbance +2SD for sera from healthy volunteers. RESULTS: In
      patients with chronic viral hepatitis, elevated anti-survivin antibodies were
      detected in 10 of 57 sera (17.5%); in HCC patients, such elevation were detected
      in 7 of 29 sera (24.1%). The levels of anti-survivin antibodies in HCC patients
      with HCV infection were significantly higher than those in the healthy control
      and HCC patients with HBV infection. However, there were no significant
      differences in the levels of anti-survivin antibodies between HCV and HCC
      patients with HCV infection. CONCLUSIONS: We demonstrated that elevated anti
      survivin antibodies were detected for the first time in patients with chronic
      viral hepatitis. The results suggest that the levels of anti-survivin antibodies
      have no association with the progression of HCV or HBV to HCC.

PMID- 16278151
TI  - Possible molecular mechanisms to account for the involvement of tryptase in the
      pathogenesis of psoriasis.
AB  - Tryptase has been suggested to take part in the pathophysiology of psoriasis
      mainly through the production of C3a by cleaving C3. However, studies using
      tryptase preparations of high purity do not support this notion. Therefore,
      although tryptase is unanimously believed to be involved in the
      immunopathogenesis of psoriasis, no convincing mechanism has been proposed for
      its role. This paper proposes several mechanisms by which this enyme may exert
      its role in the pathobiology of psoriasis. Tryptase is a mitogen for epithelial
      cells and stimulates IL-8 production and ICAM-1 expression by these cells. It
      also induces the expression of mRNA for IL-1beta and IL-8 and stimulates the
      selective release of IL-8 from endothelial cells and TNF-alpha, IL-1beta, and IL
      6 from lymphocytes and monocytes. Besides itself being a chemoattractant for
      neutrophils, tryptase activates mast cells and generates kinins from kininogen,
      thereby playing a crucial role in leukocyte infiltration into psoriatic lesions.
      This enzyme also induces leukocyte infiltration partly through activating
      endothelial PAR-2, which contributes to leukocyte rolling, adherence and
      recruitment by inducing the release of endothelial platelet-activating factor.
      Through activating PAR-2, tryptase could also trigger the development of
      Langerhans cells which play a crucial role in the pathophysiology of psoriasis.
      This enzyme is a mitogen for fibroblasts, which are probably involved in the
      pathophysiology of psoriasis through production of insulin-like growth factor-I
      (IGF-I). Tryptase is a gelatinase and also activates stromelysin-1 (MMP-3),
      thereby contributing to the disruption of psoriatic basement membrane and to the
      joint damage seen in psoriatic arthritis. Increase of tryptase levels following
      trauma could also provide a mechanism for Koebner phenomenon seen in psoriasis.

PMID- 16278152
TI  - Dietary consumption of Echinacea by mice afflicted with autoimmune (type I)
      diabetes: effect of consuming the herb on hemopoietic and immune cell dynamics.
AB  - Epidemiological studies indicate that the incidence of Type 1 diabetes, an
      autoimmune disease, is rising rapidly. However, none of the current therapies
      produces life long remission, or can prevent the disease onset. The NOD (non
      obese diabetic) mouse is currently regarded as an excellent animal model of human
      Type 1 diabetes. NKT cells are known to be fundamental in modulating the disease,
      yet they are numerically and functionally deficient in mammals bearing this
      disease. Indeed, the role of NK cells in inhibiting autoimmunity in general is
      well established. Immunoregulatory strategies are currently believed to be the
      way of the future with respect to modulating autoimmune diseases. Based on this
      hypothesis, and the fact that the herb, Echinacea, is a well demonstrated
      immunostimulant of NK cells in normal mice/humans, we aimed to investigate, in
      NOD mice, the effect of short term (days) and long term (months) daily dietary
      administration of Echinacea, on the absolute levels of NK cells, and five other
      classes of hemopoietic and immune cells, in the bone marrow and spleen. The
      results revealed that, in NOD mice, dietary Echinacea, resulted in a significant
      increase in the absolute numbers of NK cells, irrespective of feeding duration,
      in the spleen, and moreover, it actually stimulated NK cell production in their
      bone marrow birth site. We further found that there were transient, early (days),
      herb exposure-time-dependent, quantitative changes in several of the other
      hemopoietic and immune cells populations in both the bone marrow and spleen. We
      conclude that consumption of this herb by NOD mice, at least, has lead to no
      negative repercussions with respect to the hemopoietic and immune lineages, and
      secondly, the consistent, long-lasting immunostimulation only of NK cells, may
      lead to a possible new approach to the treatment of Type 1 diabetes.

PMID- 16278153
TI  - Monoclonal antibody 2C5-mediated binding of liposomes to brain tumor cells in
      vitro and in subcutaneous tumor model in vivo.
AB  - This study aimed to investigate the monoclonal antibody (mAb) 2C5 with nucleosome
      restricted specificity for its ability to specifically recognize human brain
      tumor cells and to serve as a specific ligand for liposome targeting to brain
      tumor cells in vitro and in vivo. The affinity of mAb 2C5 towards brain tumor
      cells was tested by flow cytometry. The interaction of 2C5-immunoliposomes (ILS)
      with brain tumor cells in vitro was studied by fluorescence microscopy. For in
      vivo accumulation studies, (111)In-ILS were administered i.v. into mice bearing
      subcutaneously grown brain tumor. mAb 2C5 was found to be reactive against
      several tested brain tumor cell lines. mAb 2C5 and 2C5-ILS demonstrated enhanced
      cell-surface binding with CCF-STTG1,U-87 MG and LN-18 cells in vitro. 2C5-ILS
      displayed significantly better accumulation in the subcutaneously grown brain
      tumor than non-specific control IgG-ILS. mAb 2C5 specifically recognizes brain
      tumor cells and can serve as a ligand to target drug carriers such as liposomes
      to brain tumor cells in vivo.

PMID- 16278154
TI  - Tumour gene expression from C12 spermine amphiphile gene delivery systems.
AB  - Gene therapy requires safe and efficient gene delivery systems. Towards this aim
      both the gene formulation and tumour transfection ability of C12 spermine
      amphiphiles were tested. Five amphiphiles were synthesised and characterised: 1
      [N,N-bis(3-aminopropyl)-1,4-butane diamine] dodecane (12G0--a C12 spermine
      amphiphile), a poly(ethylene glycol) (PEG, MW = 2 kDa) derivative of 12G0, 1,12
      [N,N-bis(3-aminopropyl)-1,4-butane diamine] dodecane (12G1--a C12 spermine
      bolaamphiphile) and N-methyl quaternary ammonium derivatives of both 12G0 (12QG0)
      and 12G1 (12QG1). All amphiphiles except 12G0, which precipitates, yield
      nanoparticles in aqueous media with and without DNA. Thus when 12G0 is
      substituted with either quaternary ammonium or PEG groups it forms nanoparticles
      both with and without DNA. The minimum nitrogen, phosphate ratio required to
      completely condense DNA (NP) was inversely proportional to the particles' zeta
      potential (zeta), NP = 1626/zeta(0.98). Biological testing showed that both PEG
      and quaternary ammonium groups diminished the membrane lytic ability of these C12
      amphiphiles. On intratumoural injection, while PEG groups hamper gene transfer,
      the quaternary ammonium amphiphile (12QG0) produces tumour confined gene
      expression that is 80% of that produced by linear poly(ethylenimine) (LPEI, MW =
      22 kDa); while the intratumoural injection of LPEI produced significant gene
      expression in the liver and lung, making 12QG0 suitable for the administration of
      cytotoxic tumouricidal genes.

PMID- 16278155
TI  - Hepatitis B surface protein docked vesicular carrier for site specific delivery
      to liver.
AB  - The intrinsic liver tropism of liposomes can be augmented by the addition of
      targeting features such as the incorporation of hepatotropic elements of the
      hepatitis viruses. Hepatitis B virus is known to infect hepatocytes after viremia
      by asialoglycoprotein receptor mediated uptake. However, the specificity of
      hepatitis B virus surface protein (HBsAg) towards hepatocytes has confronting
      reports. In the present study, we evaluated the functional ability of HBsAg to be
      employed as a ligand for targeting hepatocytes. We prepared (14)C labeled small
      unilamellar vesicles (SUVs) composed of egg PC/Cholesterol/N
      glutarylphosphatidylethanolamine (NGPE) in a 60:30:10 molar ratio. HBsAg was
      covalently linked to SUVs using a water-soluble carbodiimide (EDC) mediated
      conjugation with NGPE. In vitro cell binding and uptake studies revealed that
      bioprotein docked carrier system was efficiently taken up by HepG2 cells by the
      receptor mediated endocytosis. The biodistribution behaviour of plain and HBsAg
      coated liposomes was also examined followed by intravenous injection. The study
      revealed that almost 75% of the radioactivity was recovered in the liver after 4
      h of injection that was nearly three-fold greater in magnitude than the plain
      liposomes. Further, fractionation of liver into liver parenchymal cells (PC) and
      non-parenchymal cells confirmed the preferential localization of the HBsAg coated
      liposomal carrier in the parenchymal cells.

PMID- 16278156
TI  - Crystal structure of the complex of group I PLA2 with a group II-specific peptide
      Leu-Ala-Ile-Tyr-Ser (LAIYS) at 2.6 A resolution.
AB  - Phospholipases A(2)s (PLA(2)s) are widely distributed in mammals and snake
      venoms. They catalyze the production of arachidonic acid from membrane
      phospholipids leading to the bioynthesis of pro-inflammatory eicosanoids. A
      peptide Leu-Ala-Ile-Tyr-Ser (LAIYS) was designed and synthesized as a specific
      inhibitor of PLA(2). It was shown earlier that the peptide bound to group II
      PLA(2) specifically and had a dissociation constant (K(d)) of 8.8 x 10(-9) M. In
      the present studies for the binding of LAIYS with a group I PLA(2) from Naja naja
      sagittifera using surface plasmon resonance the dissociation constant was found
      to be 4.5 x 10(-5) M which is considerably lower than the value found for the
      group II PLA(2). In order to determine the details of binding at the molecular
      level, a group I PLA(2) from the venom of Naja naja sagittifera was crystallized
      with peptide LAIYS. The crystal structure showed the presence of LAIYS at the
      substrate-binding site but has fewer interactions than those observed with group
      II PLA(2) from Daboia russelli pulchella. The observed difference in the binding
      affinity is caused primarily due to poor fitting of the peptide LAIYS in the
      binding site of group I PLA(2). Apparently, the location of Trp 19 in group I
      PLA(2) is not favourable for the binding of LAIYS. The two complexes also differ
      drastically in the formation of intermolecular interactions. In the present
      structure, the side chain of Ser (P) interacts with His 48 and Asp 49 while in
      the complex with group II PLA(2) it was Tyr (P) OH that formed the corresponding
      interactions. Tyr (P) in group I PLA(2) is the main contributor of the
      hydrophobic interactions whereas in the complex of LAIYS with group II PLA(2) it
      was the peptide segment Leu-Ala-Ile that produced the bulk of hydrophobic forces.
      The structures further showed that the peptide LAIYS was fully inside the
      substrate-binding region of the group II PLA(2) while a significant portion of
      the peptide LAIYS was hanging outside the surface of the group I PLA(2). The
      buried area in the complex with group II PLA(2) was 811 A(2) whereas, the
      corresponding area in group I PLA(2) was 449 A(2). This shows that the peptide
      LAIYS is very compatible with the substrate-binding site of group II PLA(2) and
      rather poorly fits into the substrate-binding site of group I PLA(2). This
      indicates that a highly specific ligand for one form of PLA(2) may be a poor
      partner for another form of enzyme.

PMID- 16278157
TI  - Use of liposomized tetracycline in elimination of Wolbachia endobacterium of
      human lymphatic filariid Brugia malayi in a rodent model.
AB  - Wolbachia bacteria, being filarial parasite symbiont have been implicated in a
      variety of roles, including development, fecundity and the pathogenesis of the
      filarial infections. Among various strategies used in the treatment of
      experimental filariasis, the elimination of symbiont Wolbachia seem to offer an
      efficient means of curing the disease. The antiwolbachial property of
      tetracycline has been well worked out; however, treatment needs to be continued
      for a prolonged period of time to achieve complete elimination of Wolbachia from
      the filarial parasites and their subsequent killing. This results in acute
      toxicity, thus limiting its practical utility for clinical implementation. In
      order to increase efficacy of the antibiotic with minimal toxic manifestations,
      we developed liposomized formulation of the tetracycline. The liposomized
      tetracycline was found to be significantly more effective when compared to the
      free form of the drug. In contrast to the 90/120 days oral administration of the
      drug, the treatment schedule using the liposomized form of the drug was reduced
      to 12 alternate days with better efficacy of the treatment.

PMID- 16278159
TI  - Stem cell transplantation--a new era in medicine?

PMID- 16278158
TI  - Absorption of interferon alpha from patches in rats.
AB  - Interferon alpha (IFN-alpha), patch preparations composed of three layers, water
      insoluble backing layer, drug containing layer with absorption enhancer and
      surface layer containing pH-dependent polymer were prepared. As absorption
      enhancer, three surfactants, Gelucire44/14 (Lauroyl macrogol-32 glycerides),
      Labrasol (Caprylocaproyl macrogol-8 glycerides) and HCO-60 (polyoxyethylated
      hydrogenerated castor oil) were used in preparing IFN-alpha patch preparations.
      The intestinal absorption of IFN-alpha was studied after the administration of
      test patch preparations into the rat jejunum, 50,000 IU/kg. The serum IFN-alpha
      levels were measured by an ELISA method and both C(max) and AUC were determined
      as the index of absorption of IFN-alpha. Gelucire44/14 preparation including
      Pharmasol for the stable solidification showed the higher C(max), 7.66 +/- 0.82
      IU/ml, and AUC, 12.85 +/- 1.49 IU h/ml, than Labrasol (6.51 +/- 0.89 and 8.30 +/-
      1.34 IU h/ml) and HCO-60 (6.02 +/- 1.14, 7.53 +/- 1.84 IU h/ml) preparations,
      respectively. By comparing to the AUC obtained after s.c. injection of the same
      dose of IFN-alpha to rats, bioavailability (BA) was estimated to be 7.8% in
      Gelucire44/14 preparation. In vitro release study showed that the T50%s, the time
      when half of the formulated IFN-alpha is released from the patches, were 3.4 +/-
      0.1 min for HCO-60, 7.8 +/- 0.1 min for Gelucire44/14 and 11.4 +/- 0.1 min for
      Labrasol preparations. To study the effect of absorption site, Gelucire44/14
      preparation was administered into the rat duodenum and ileum. However, there were
      not significant differences on AUC among the three absorption sites. By reducing
      the IFN-alpha dose from 50,000 to 25,000 IU/kg, the serum IFN-alpha levels vs
      time profile showed a tendency of dose-dependency. When the histological
      examination of small intestinal mucosa was carried out in this study, the small
      intestinal mucosa after the Gelucire44/14 patches administered and before it was
      administered, could not recognize impaired. From these results, the usefulness of
      oral patch system for the oral delivery of IFN-alpha has been proved in rats.

PMID- 16278160
TI  - Mesenchymal stem cells.
AB  - About 40 years ago Friedenstein described stromal cells in the bone marrow that
      were spindle shaped and proliferate to form colonies. These cells attach to
      plastic and are able to differentiate under defined in vitro conditions into
      multiple cell types present in many different tissues, e.g. osteoblasts,
      chondroblasts, adipocytes, etc. Later on these cells, obtained from postnatal
      bone marrow, were called mesenchymal stem cells (MSC) or stromal stem cells.
      Recently the presence of somewhat similar cells has been demonstrated in many
      other tissues too. In spite of extensive attempts to characterize these cells we
      are still lacking definitive in vivo markers of MSC although retrospective
      functional data strongly support the existence of common adult stem cells that
      have the capacity to differentiate along various specific differentiation
      lineages. Since MSC can be rather easily isolated from the bone marrow and can
      also be expanded in vitro they have become a prime target for researchers of
      tissue regeneration. These cells have now been extensively used for
      transplantation experiments in animals and also for some therapeutic trials in
      humans. However, much new research is needed to learn enough on the molecular
      mechanisms of MSC differentiation to evaluate their full capacity for tissue
      regeneration.

PMID- 16278161
TI  - New neurons in old brains.
AB  - The brain was traditionally viewed as a static organ, without turnover of neurons
      or significant capacity for self-repair after insults. Research in the last years
      has established that neurons are renewed in certain areas throughout life. The
      prospect of stimulation of endogenous neurogenesis as well as cell
      transplantation has raised hope for new therapies for neurological diseases.

PMID- 16278162
TI  - Stem cell-based therapy for Parkinson's disease.
AB  - Motor dysfunctions in Parkinson's disease are considered to be primarily due to
      the degeneration of dopaminergic neurons in the substantia nigra pars compacta.
      Pharmacological therapies based on the principle of dopamine replacement are
      extremely valuable, but suffer from two main drawbacks: troubling side effects
      (e.g. dyskinesia) and loss of efficacy with disease progression. Transplantation
      of embryonic dopaminergic neurons has emerged as a therapeutic alternative.
      Enthusiasm following the success of the initial open-label trials has been
      dampened by the negative outcome of double-blind placebo controlled trials.
      Additionally, the emergence of graft-related dyskinesia indicates that the
      experimental grafting procedure requires further refinement before it can be
      developed into a therapy. Shortage of embryonic donor tissue limits large-scale
      clinical transplantation trials. We review three of the most attractive tissue
      sources of dopaminergic neurons for cell replacement therapy: human embryonic
      ventral mesencephalic tissue, embryonic and adult multipotent region-specific
      stem cells and embryonic stem cells. Recent developments in embryonic stem cell
      research and on their implications for a future transplantation therapy in
      Parkinson's disease are described. Finally, we discuss how human embryonic stem
      cells can be differentiated into dopaminergic neurons, and issues such as the
      numbers of dopaminergic neurons required for success and the risk for teratoma
      formation after implantation.

PMID- 16278163
TI  - Cardiomyocytes derived from stem cells.
AB  - One way to restore failing heart function following myocardial infarction would
      be to replace lost or damaged cardiac cells by local or systemic injection. The
      sources of replacement cells presently discussed include embryonic stem cells,
      hematopoietic and non-hematopoietic stem cells from bone marrow or cord blood and
      small stem cell populations thought to reside in the heart itself or in skeletal
      muscle. Here we review this area of stem cell research with focus particularly on
      recent laboratory advances towards producing cardiomyocytes from embryonic stem
      cells. We conclude that embryonic stem cells and cardiac progenitors in the heart
      itself are the only proven sources of cardiomyocytes and that reported clinical
      effects of bone marrow stem currently undergoing validation are likely mediated
      by other mechanisms.

PMID- 16278164
TI  - Stem cells in the treatment of diabetes.
AB  - Clinical islet transplantation trials based on cadaveric allogenic islets have
      demonstrated that it is indeed possible to restore near-physiological insulin
      secretion capacity in a type 1 diabetic patient through transplantation of
      insulin-producing cells. In order to develop this form of therapy to become
      available for the vast majority of patients with diabetes, new sources of
      transplantable insulin-producing cells need to be identified. Stem cells provide
      the best potential to achieve this goal. Controversial results have been
      presented concerning the existence and nature of pancreatic islet stem or
      precursor cells. An increasing body of evidence suggests that the pancreatic and
      hepatic cell types (hepatocytes, islet, acinar and ductal cells) have remarkable
      plasticity and can de- and trans-differentiate into each other under appropriate
      conditions. Elucidation of the molecular mechanisms regulating these processes
      could lead to clinically applicable ways of either inducing pancreatic islet
      regeneration in situ or to expanding the insulin-producing cells in vitro for
      transplantation. The emergence of human embryonic stem cells has led to an active
      area of research aiming to achieve targeted differentiation of these cells into a
      safely transplantable beta-like cell. After initial excitement, it appears that
      much basic research is still required before this goal could be achieved.

PMID- 16278165
TI  - Human embryonic stem cells: possibilities for human cell transplantation.
AB  - Human embryonic stem (ES) cells serve as a potentially unlimited renewable source
      for cell transplantation targeted to treat several diseases. One advantage of
      embryonic stem (ES) cells over other stem cells under research is their
      apparently indefinite self-renewal capacity if cultured appropriately, and their
      ready differentiation into various cell phenotypes of all three germ layers. To
      date, a number of studies have reported the derivation of specific functional
      derivatives from human ES cells in vitro. While there have been clinical trials
      of human embryonal carcinoma (EC) cell-derived neurons in humans there has been
      no attempt as yet using human ES cell derivatives. However, the latter have been
      transplanted into recipient animals. In some cases ES-derived cells were shown to
      undergo further maturation, displayed integration with host tissue and even
      ameliorated the disease condition in the animal model. Recently, it has been
      reported that human ES cells can be genetically manipulated. Such procedures
      could be used to direct differentiation to a specific cell type or to reduce
      graft rejections by the modification of immune responses. This review highlights
      some of the recent advances in the field and the challenges that lie ahead before
      clinical trials using ES-derived cells can be contemplated.

PMID- 16278166
TI  - Stem cell transplantation in autoimmune diseases: an update.
AB  - Immunosuppressive or immunomodulatory treatments are often used in patients with
      various autoimmune diseases (AID). However, since conventional treatments are
      rarely curative, alternative treatment methods have been looked for. Based on
      animal experiments and anecdotal case reports, stem cell transplantation (SCT)
      has received considerable attention in the treatment of severe autoimmune
      diseases during the last decade. This review summarizes current experience of SCT
      in patients this field. Although early experience shows some promise, randomized
      studies are necessary to evaluate the real value of autologous SCT in various
      autoimmune diseases. Since autologous SCT may not be curative in patients with
      AID, also evaluation of allogeneic SCT is important in the future.

PMID- 16278167
TI  - Mild hyperthermia plus adenoviral p53 over-expression additively inhibits the
      viability of human malignant glioma cells.
AB  - Adenoviral replacement of the p53 gene has already been proved effective for the
      treatment of various tumours, including malignant gliomas. However, it is
      difficult to treat malignant glioma with p53 gene therapy alone because of
      problems with resistance or a less-than-satisfactory response to the treatment.
      This study investigated whether heat shock at 43 degrees C (mild hyperthermia)
      augments the cytotoxic effect of p53 gene transfer on malignant glioma cells
      expressing wild-type p53 (D54) or mutant p53 (U373-MG and U251-MG). The
      combination of mild hyperthermia and adenoviral p53 over-expression had an
      additive inhibitory effect on cellular proliferation in all three cell lines
      studied. Further, both cell cycle analysis and a DNA fragmentation assay showed
      that apoptosis was induced by p53 over-expression alone but not by heat shock at
      43 degrees C alone. However, p53 over-expression followed by mild hyperthermia
      additively increased the proportion of cells in which apoptosis was induced,
      regardless of the endogenous p53 status of the tumour cells. Interestingly, a
      caspase-independent mechanism was observed to be involved in the p53-induced
      apoptosis in U251-MG and D54 cells. Taken together, the findings showed that
      combining adenoviral p53 transfer with mild hyperthermia inhibits the
      proliferation of malignant glioma cells in an additive manner, irrespective of
      their endogenous p53 status, suggesting a novel treatment strategy for this
      malignancy.

PMID- 16278168
TI  - Hyperthermia combined with radiation in treatment of locally advanced prostate
      cancer is associated with a favourable toxicity profile.
AB  - PURPOSE: Hyperthermia is used to treat several pelvic tumours. An important step
      in establishing a broader role for hyperthermia in treatment of prostate cancer
      is verification of an acceptable toxicity profile. In this report, short- and
      long-term toxicity profiles of a completed phase II trial of transrectal
      ultrasound hyperthermia combined with radiation in treatment of locally advanced
      prostate cancer are presented. METHODS AND MATERIALS: Thirty-seven patients
      enrolled on a phase II study of external beam radiation +/- androgen suppression
      with two transrectal ultrasound hyperthermia treatments were assessed for short-
      and long-term toxicity. Prostatic and anterior rectal wall temperatures were
      monitored. Rectal wall temperatures were limited to 40 degrees C (19 patients),
      41 degrees C (three patients) and 42 degrees C (15 patients). Univariate logistic
      regression was used to estimate the log hazard of developing NCI CTC Grade 2
      toxicity based on temperature parameters. Hazard ratios, 95% confidence
      intervals, p-values for statistical significance of each parameter and proportion
      of variability explained for each of the parameters were calculated. RESULTS:
      Median follow-up was 42 months. Both short- and long-term GI toxicity were
      limited to grade 2 or less. Acute grade 2 proctitis was greater for patients with
      allowable rectal wall temperature of >40 degrees C. Eleven of 18 patients in this
      group had acute grade 2 proctitis vs three of 19 patients with rectal wall
      temperatures limited to 40 degrees C (p = 0.004). Long-term grade 2 GI and GU
      toxicity occurred in 5% and 19% of patients. No late grade 3 or greater toxicity
      occurred. Late GI and GU toxicity were not associated with the allowable rectal
      wall temperature. CONCLUSION: Transrectal ultrasound hyperthermia combined with
      radiation for treatment of advanced clinically localized prostate cancer is safe
      and well tolerated.

PMID- 16278169
TI  - Improved magnetic resonance thermal imaging by combining proton resonance
      frequency shift (PRFS) and apparent diffusion coefficient (ADC) data.
AB  - Effective thermal therapy for cancer is dependent on adequate tumor heating.
      Adequate heating, in turn, is dependent on reliable volumetric measurement of
      temperature to guide heating. Proton resonance frequency shift (PRFS) magnetic
      resonance imaging is frequently used for the purpose of three-dimensional
      temperature imaging. However, this method is susceptible to drift in the imaging
      magnetic field, leading to a corresponding drift in the measured temperature. A
      new approach to correcting for this drift is presented. It combines PRFS imaging
      alternated with water apparent diffusion coefficient (ADC) imaging to yield
      resulting thermal images that are drift corrected and possess the complementary
      strengths of the two methods. The drift-corrected PRFS images retain the high
      resolution and relatively noise-free characteristic of PRFS imaging while adding
      on the drift-free stability of ADC imaging. This technique is successfully
      demonstrated in a phantom experiment. This technique is also applicable to
      correcting motion-induced sudden large discontinuities in PRFS imaging, although
      not explicitly demonstrated in this work.

PMID- 16278172
TI  - Hip fractures in elderly patients - perspectives towards the future.

PMID- 16278173
TI  - Scoring systems to evaluate elderly patients with hip fractures.
AB  - PURPOSE: To report about different scales and scoring systems used to evaluate
      elderly patient with hip fracture during the acute post-fracture phase and during
      post-operative rehabilitation. METHODS AND RESULTS: Report of the different
      scales from a literature review. CONCLUSIONS: Standard validated scales are one
      of the tools to perform such an evaluation process as objectively as possible and
      to evaluate surgical, medical and rehabilitative management in these elderly
      patients. These scales are only a complementary tool, and they cannot replace
      physical examination. However, these validated tools are probably more accurate
      than just clinical impression. The appropriate combination of clinical experience
      and these scales may well contribute to a better care of elderly patients with
      hip fractures.

PMID- 16278174
TI  - Clinical pathway after hip fracture.
AB  - PURPOSE: Hip fracture occurs frequently, resulting in considerable morbidity,
      mortality and utilization of healthcare resources. Technical advances in fracture
      fixation and surgical treatment have improved outcomes following hip fracture in
      the elderly. However, further improvement in outcomes of hip fracture patients
      may be possible with utilization of a clinical pathway designed to enhance
      outcomes in a standardized, cost-effective manner. This paper presents a clinical
      pathway for the treatment of hip fractures in the elderly with the above aims.
      METHOD: The clinical pathway presented is based on personal experience and
      literature pertaining to the treatment of the elderly hip fracture patient. It
      outlines a suggested algorithmic approach to the patient that begins with the
      initial evaluation, progresses on through pre-operative and operative management,
      and ends with post-operative rehabilitation and treatment. RESULTS: The clinical
      pathway for the hip fracture patient in this paper is a working treatment
      algorithm that has been successful in personal experience. CONCLUSION: This
      treatment algorithm has been utilized successfully in personal experience.
      Further input from healthcare professionals may prove to enhance outcomes in a
      cost-effective, standardized manner.

PMID- 16278175
TI  - Prevention of falls in older people.
AB  - In recent years the evidence base for prevention of falls in older people has
      increased and associated with this has been an inevitable expansion in clinical
      services which attempt to localize and implement what is described in the
      literature. This article reviews the basic physiology implicit in maintenance of
      the upright posture; highlights the diversity of medical and non-medical risk
      factors associated with falls; describes the clinical assessment of an older
      person at risk of falls; reviews the evidence for intervention in the prevention
      of falls in older people; and acknowledges the need for a clear strategic
      direction to successfully prevent falls and the requirement for ongoing research
      as well as much needed service evaluation.

PMID- 16278176
TI  - Predicting the success of rehabilitation following hip fractures.
AB  - PURPOSE: To review what predictors are of positive or negative value in the
      rehabilitation procedure following hip fractures. METHOD: Reviewing a doctorial
      thesis on prognosis and rehabilitation of elderly with a hip fracture from 1980
      and then review the literature on this subject for the following quarter of a
      century. RESULTS: In the Western world the short-term prognosis for early return
      home after sustaining a hip fracture depends on the success of the operation
      allowing independent walking and basic activities of daily life, no debilitating
      disease and having someone at home. The one-year prognosis for having returned
      and remained at home requires a reasonable good health irrespective of living
      alone and a somewhat deteriorated hip function. CONCLUSIONS: It is difficult to
      make comparisons with studies of other populations and other time periods.
      Different predictors of the rehabilitation are used and the definitions of these
      are not always the same. They are of varying weight, can change with time and may
      be interdependent of each other. For example, general medical condition and age
      are strongly interrelated predictors but age alone is less important than
      concomitant disease for the success of the rehabilitation. Nevertheless, already
      on admission of a patient with a fresh hip fracture a reliable prognosis can be
      done. However, such a prediction must be guided by ethical, social and scientific
      concerns.

PMID- 16278177
TI  - Influence of age, sex, fracture type and pre-fracture living on rehabilitation
      pattern after hip fracture in the elderly.
AB  - PURPOSE: To evaluate the influence of background factors on the rehabilitation
      pattern after a hip fracture in the elderly. METHOD: Prospective registration
      based on the Swedish national register for hip fracture patients called
      RIKSHOFT/SAHFE (Standardised Audit of Hip Fractures in Europe). The place of
      living was registered both before fracture and during the following four months
      period (120 days). Graphs were calculated and drawn based on day-to-day changes.
      Also influences of age, sex, fracture type and type of operation were analyzed.
      RESULTS: The patient's pre-fracture functional capacity as evidence by the place
      they were able to manage to live before the fracture was the most discriminating
      factor for the rehabilitation; more than sex, fracture type or type of operation.
      Age was also a highly discriminating factor with a pronounced influence on the
      rehabilitation pattern. CONCLUSIONS: These background parameters are very
      important factors when planning the rehabilitation of hip fracture patients. A
      strategy with individualized planning of the rehabilitation procedure will be
      highly necessary in the future, in view of the increasing amount of elderly with
      hip fractures prognosticated during the coming decades. The knowledge about
      influencing factors here presented will be useful when planning and performing
      the rehabilitation for this resource-consuming group of patients.

PMID- 16278178
TI  - Audit, guidelines and standards: clinical governance for hip fracture care in
      Scotland.
AB  - PURPOSE: To report on experience of national-level audit, guidelines and
      standards for hip fracture care in Scotland. METHODS: Scottish Hip Fracture Audit
      (from 1993) documents case-mix, process and outcomes of hip fracture care in
      Scotland. Evidence-based national guidelines on hip fracture care are available
      (1997, updated 2002). Hip fracture serves as a tracer condition by the health
      quality assurance authority for its work on older people, which reported in 2004.
      RESULTS: Audit data are used locally to document care and support and monitor
      service developments. Synergy between the guidelines and the audit provides a
      means of improving care locally and monitoring care nationally. External review
      by the quality assurance body shows to what extent guideline-based standards
      relating to A&E care, pre-operative delay, multidisciplinary care and audit
      participation are met. CONCLUSION: Three national-level initiatives on hip
      fracture care have delivered: Reliable and large-scale comparative information on
      case-mix, care and outcomes; evidence-based recommendations on care; and
      nationally accountable standards inspected and reported by the national health
      quality assurance authority. These developments are linked and synergistic, and
      enjoy both clinical and managerial support. They provide an evolving framework
      for clinical governance, with casemix-adjusted outcome assessment for hip
      fracture care as a next step.

PMID- 16278179
TI  - Evaluation of 238 consecutive patients with the extended data set of the
      Standardised Audit for Hip Fractures in Europe (SAHFE).
AB  - PURPOSE: The aim of this paper is to introduce the extended data set inquiries of
      the Standardised Audit of Hip Fractures in Europe (SAHFE) and to report our
      experiences of its use. METHOD: The extended SAHFE data set was applied to 238
      consecutive patients (mean age 78.4 (50 - 102) years, 52 males, 186 females) aged
      over 50 years with non-pathological fractures of the hip. The extended data set
      contains 95 questions concerning the patient's abilities prior fall and at follow
      up, detailed background factors, concomitant diseases, additional details of the
      injury, treatment, fracture type and reduction and complications. RESULTS: Thirty
      nine percent of the fractures occurred at home and 38% in a hospital. Thirteen
      percent of the cervical fractures were non-displaced (Garden 1 & 2) and half of
      the trochanteric fractures intertrochanteric two-part fractures (A11 - A13). The
      mean Garden alignment index evaluated from antero-posterior roentgenograms
      changed from the preoperative 144 degrees to the postoperative 168 degrees and
      that from lateral projections from 144 degrees to 171 degrees , respectively.
      Most of the patients (89%) had associated diseases, especially cardiovascular
      conditions. The patients' functioning was significantly impaired at four months
      compared with the preoperative situation according to the ADL score. The need for
      social support and assistance had increased, respectively. A total of 63% of the
      surgeries were delayed for more than 24 hours. Low molecular weight heparin was
      given to every patient for thromboembolic prophylaxis and 92% received antibiotic
      prophylaxis. Urinary tract (21%) and chest infections (7%) were the most common
      complications. The deep infection rate was 2.5%. CONCLUSION: The extended SAHFE
      data set is useful and makes it possible to study in more detail the background
      and outcome factors of hip fractures in a standardized manner.

PMID- 16278180
TI  - To what extent are carers involved in the care and rehabilitation of patients
      with hip fracture?
AB  - PURPOSE: To examine the carer's role regarding early hospital rehabilitation.
      METHOD: A qualitative study, using semi-structured interviews with 30 carers. A
      convenience sample was obtained through participants volunteering for the study.
      Interviews were of 30 - 45 minutes duration and were audiotaped. The transcripts
      were read in their entirety by all authors. Main themes were identified and
      coded. RESULTS: Twenty women and ten men were recruited, who cared for 22 women
      and eight men. A third of the interviewees reported other caring
      responsibilities. Carers performed a range of tasks for the patient and most
      revolved around the key activity of hospital visiting. A range of functions were
      undertaken, including: help with eating and drinking; providing the opportunity
      for social interaction; acting as a link between the external world and hospital;
      and offering emotional support. CONCLUSIONS: Carers not only provided practical
      help but also offered psychological support. Our study highlights the key role of
      carers in the rehabilitation of patients with hip fracture and provides support
      for the recommendation that family members should be provided with information
      regarding rehabilitation. Carers need to be regarded as a resource by hospital
      staff, given their key role in enhancing patient motivation.

PMID- 16278181
TI  - Five-year experience with the 'Sheba' model of comprehensive orthogeriatric care
      for elderly hip fracture patients.
AB  - BACKGROUND AND PURPOSE: The Sheba model of orthogerioatric medicine is a unique
      model of in-hospital care for elderly hip fractured patients, based upon the
      concept that a hip fracture represents a geriatric, rather than an orthopedic
      disease. The nature and feasibility of such a comprehensive orthogeriatric unit,
      taking care of all surgical, medical and rehabilitation needs, in a single
      geriatric-based setting (rather than orthopedic-based), were questioned. The aim
      of the study is to describe the results of its operation during a five-year
      period. METHOD: A retrospective charts analysis of consecutive older patients
      with hip fractures, admitted from the emergency unit directly to the
      orthogeriatric unit of a department of geriatric medicine. RESULTS: A total
      number of 592 patients were admitted. Mean age of patients was 83.2 years, mostly
      women. A total of 538 (91%) were treated surgically. Delay to surgery was 3.6 +/-
      2.9 days. A total of 65.6% were suitable for rehabilitation, and had a mean
      Functional Independence Measure (FIM) gain of 22.3 +/- 7.9. Mean total hospital
      length of stay was 29.9 days and 68.7% of patients returned to their previous
      living residence. Rates of major complications (4.1%) and in-hospital mortality
      (3.2%, equivalent to 30 days mortality) were low. CONCLUSIONS: Treatment within
      this unit was associated with low rates of major morbidity and mortality, short
      stay and acceptable functional outcomes. The data provide clinical evidence
      supporting the implementation of this model of comprehensive orthogeriatric care,
      being a practical, applicable and feasible service for elderly hip fractured
      patients, and covering the various needs of these patients. The present model of
      organization could also help in skillful use of economic resources, facilitating
      effective treatment strategies.

PMID- 16278182
TI  - Costs and consequences of hip fracture occurrence in old age: an economic
      perspective.
AB  - PURPOSE: To summarize the reported short- and long-term costs associated with hip
      fracture occurrence in old age, based on a systematic literature review of
      published studies. A further aim is to provide a clinician-oriented discussion of
      the different types of economic evaluations, with an emphasis on studies that
      examined potential determinants of the costs of care after hip fracture. METHOD:
      Literature review. MAIN RESULTS: Even after the initial hospitalization, hip
      fractures continue to generate significant costs throughout the one-year period
      after discharge, but particularly during the first three months. Cost estimates
      based on data obtained prospectively from hip-fracture patients and matched
      controls showed that the costs associated with the treatment of hip-fracture
      patients are about three times greater than those resulting from the treatment of
      age and residence-matched controls without a fracture. Two-fifths of these excess
      costs are incurred during the first three months following hospital discharge.
      Increasing age at the time of injury and living in an institution before the
      fracture are among the most important determinants of an increased cost of care
      after hospital discharge. Programs that focus on continuity of care, adopt a
      multidisciplinary approach, and accelerate rehabilitation have shown to be able
      to reduce the cost of care after hip fracture. CONCLUSIONS: This review
      emphasizes the importance of current and future interventions to decrease the
      incidence of hip fracture. While the current review cannot provide definite
      answers to the questions of cost containment, our review provides critically
      important evidence about the need to base health policy decisions on empirical
      observations. Comprehensive economic analyses of financial costs and health
      outcomes are needed to develop cost-effective strategies.

PMID- 16278183
TI  - Orthopaedic treatment of displaced femoral neck fractures in elderly patients.
AB  - PURPOSE AND METHOD: A review article concerning orthopaedic treatment and
      rehabilitation of displaced femoral neck fractures, focusing on evidence-based
      knowledge. RESULTS: Properly performed randomized controlled studies comparing
      internal fixation and primary arthroplasty provides the best basis to decide
      which method should be used. During the last decade, several such studies have
      been published, in addition to a few earlier works. After internal fixation with
      pins, screws or sliding hip screw and plate, the failure rate was 21 - 57% and re
      operations were performed in 14 - 53% of all the cases. In the studies using THA,
      the failure rate was 4 - 11% and the re-operation rate 2 - 8%. The corresponding
      numbers for hemi-arthroplasty were 3 - 23% and 0 - 24%. A primary arthroplasty
      tends to result in better function and less pain during the rehabilitation
      period. CONCLUSION: With support in evidence-based literature, an elderly patient
      with displaced femoral neck fracture should be treated with a primary
      arthroplasty. If the individual is healthy, active and mentally intact, a total
      hip arthroplasty should be performed, otherwise a hemi-arthroplasty. This
      rationale ensures fewer failures and re-operations, as well as better function
      and less pain during the rehabilitation.

PMID- 16278184
TI  - Cemented versus uncemented hip replacement for fracture of the hip.
AB  - PURPOSE: Review cemented versus uncemented hemi-arthroplasty hip replacement
      regarding morbidity and long term results. METHODS: A literature review searching
      PubMed and Medline was done. Publications applicable to hip fractures treated by
      hip replacement or hemi-arthroplasty replacement were reviewed. RESULTS: Several
      articles compared cemented femoral stems to fracture fixation. There were few
      articles comparing cemented and uncemented stems. Some noted increased problems
      with uncemented stems but did consider design factors. Unreamed tapered stems may
      have may have fewer problems. CONCLUSIONS: Prospective studies comparing cemented
      and uncemented femoral stems are needed to determine the best form of fixation
      for patients having hip surgery following hip fracture. Tapered uncemented stems
      may offer as good a result as cemented stems, with less morbidity.

PMID- 16278185
TI  - A comparative prospective study of dynamic variable angle hip screw and Gamma
      nail in intertrochanteric hip fractures.
AB  - PURPOSE: To compare the results between a variable angle dynamic screw-plate(DMS)
      and the Gamma nail in the treatment of intertrochanteric hip fractures. METHODS:
      A comparative prospective study of 142 patients (AO/OTA Type 31-A1; A2; A3 and
      B2) treated by variable angle dynamic screw-plate (DMS Group = 71) or by
      intramedullary nailing (Gamma Nail Group = 71). RESULTS: At the 12-month follow
      up, we did not find any statistically significant difference, intraoperatively,
      radiographically, or clinically, between the two groups of patients, except for
      shortening. In 12 patients in the DMS group (17%) and in one patient in the Gamma
      nail group, there was shortening of the operated leg between 1 cm and 3 cm (p =
      0.02). In all instances, shortening occurred in patients who sustained A.O. type
      fractures 31A2. 2 and 3 (19 patients), which are unstable and comminuted.
      CONCLUSIONS: The DMS allows effective management of intertrochanteric fractures
      of the femur. Surgeons should consider choosing surgical treatment according to
      the type of intertrochanteric fracture. In less comminuted fractures, a
      compression hip screw may be a faster and safer surgical solution. In comminuted
      fractures, surgical difficulties may increase in parallel to fracture complexity.

PMID- 16278186
TI  - Endoprosthetic replacement of unstable, comminuted intertrochanteric fracture of
      the femur in the elderly, osteoporotic patient: a review.
AB  - PURPOSE: To summarize currently existing evidence regarding prosthetic
      replacement for the treatment of intertrochanteric (extracapsular) hip fractures
      and their complications. METHOD: Report of a clinical investigation program
      conducted at one academic institution and literature review. RESULTS: Although
      the majority of intertrochanteric fractures can be successfully managed with
      operative reduction and fixation, some patients may benefit from prosthetic
      replacement. For older patients with severe osteoporosis or comminution there are
      some definite advantages of prosthetic replacement over reduction and fixation.
      If the prosthetic replacement has been properly performed, there is very little
      concern over immediate ambulation and weight-bearing. This decreases the
      incidence of postoperative complications, such as pulmonary infection,
      atelectasis, and pressure sores. In addition, acute prosthetic replacement
      eliminates the possibility of excessive collapse compromising walking function,
      mal-union, as well as the uncommon problems of non-union and avascular necrosis.
      Likewise, hip arthroplasty is an effective salvage procedure after the failed
      internal fixation of an intertrochanteric fracture in an older patient. Most
      patients report good pain relief, and surprisingly few serious orthopaedic
      complications are associated with this procedure.There are, however, a number of
      methodological concerns regarding previous studies which have examined the use of
      prosthetic replacement for the treatment of comminuted intertrochanteric
      fractures or non-union in the elderly patient. Many have been small case series
      without a control group. There are few comparative studies and even fewer
      prospective, randomized controlled trials which have compared prosthetic
      replacement surgery with standard internal fixation techniques in the long run.
      CONCLUSIONS: Older patients with severe osteoporosis or comminution may benefit
      from prosthetic replacement to treat intertrochanteric fractures and non-unions.
      Overall, rigorously conducted prospective randomized clinical trials with long
      term follow-up are lacking. Despite these methodological reservations, several
      authors have reported successful prosthetic replacement for treating
      intertrochanteric fractures and their complications in elderly patients. Few
      serious orthopaedic complications are associated with these procedures, and most
      patients have good pain relief.

PMID- 16278187
TI  - Subtrochanteric fractures: current management options.
AB  - PURPOSE: To review current management options for subtrochanteric fractures of
      the femur. These fractures behave differently from other proximal femoral
      fractures and have their own management pitfalls and problems. METHOD: Articles
      were identified from Medline. Papers on the management of subtrochanteric
      fractures were assessed, and included if they contained relevant information. The
      articles were divided into groups depending on the type of management described.
      Conservative and operative management were considered separately. Operative
      management was classified according to the type of device used into
      extramedullary and intramedullary. CONCLUSIONS: Conservative management gives
      satisfactory results in 56% of patients compared to 70 - 80% for operative
      methods. The studies on conservative methods are mostly dated, with less
      stringent outcome measures. Conservative management is safe, and has a low
      frequency of non-union. It is most applicable in regions where facilities are
      suboptimal, in patients unfit for surgery, and in children. When considering
      operative management, intramedullary devices appear to give better results than
      extramedullary devices, particularly when the medial buttress of the proximal
      femur is compromised. However, when operative treatment is undertaken, it should
      be by experienced surgeons using the technique with which they are most familiar.

PMID- 16278188
TI  - Preoperative skin traction or pillow nursing in hip fractures: a prospective,
      randomized study in 123 patients.
AB  - PURPOSE: To study the influence on pain and handling of different preoperative
      immobilization procedures for hip fractures. METHOD: 123 consecutive patients
      with displaced cervical and trochanteric hip fractures were randomized to skin
      traction, placement in a special foam pillow (Lasse pillow), and comfortable
      placement with an ordinary pillow under the hip from admission to operation. The
      effect on pain alleviation was evaluated with a Visual Analogue Scale and by the
      number of doses of analgesics administered. The processing time through the
      emergency department, X-ray department and to the ward as well as time to
      operation was registered. RESULTS: No clinically significant difference in the
      VAS pain evaluation was found. There was no difference in the total consumption
      of analgesics in the emergency department or on the ward and no effect of
      immobilization type on the processing time or time to operation. Fracture type
      did not affect the outcome. Approximately one third of the patients found
      placement on a regular pillow or the application of skin traction uncomfortable
      as opposed to only one of 19 of the patients lying in the special Lasse pillow.
      There was no other difference in processing time with regard to different forms
      of pillow nursing and skin traction. CONCLUSION: The most convenient
      immobilization should be chosen as there is no significant difference concerning
      pain and handling time. Increased attention to analgesic medication and rapid
      handling to be operated are of importance to promote the rehabilitation process.

PMID- 16278189
TI  - Brain atrophy evaluated by computed tomography in independent and
      institutionalized hip fracture patients.
AB  - PURPOSE: To examine if there is an association between brain computed tomography
      (CT) findings and place of residence in a series of hip fracture patients.
      METHOD: The CT scans taken immediately after hip fracture of 215 patients (mean
      age 81.6 years) living in their own homes or otherwise independently (home
      dwelling group) and 95 patients (mean age 82.5 years) permanently
      institutionalized (institutionalized group) were analysed. RESULTS: The
      institutionalized patients had significantly more cortical cerebral (frontal, p =
      0.004; temporal, p = 0.007; parietal, p < 0.001) and central cerebral (third
      ventricle width, p < 0.001; frontal horn width, p < 0.001; midbody width, p <
      0.001) atrophy than the home-dwelling ones. This was also true of atrophy in the
      white-matter (WM) area (p < 0.001). The institutionalized patients also had more
      atrophy of the cerebellar hemisphere (atrophy of the cerebellopontine angle
      cistern, p = 0.002, greater fourth ventricle width, p = 0.020). No significant
      difference was seen in the incidence of brain infarcts. CONCLUSIONS: Hip fracture
      patients living in institutions have more brain atrophy than those living
      independently. The brain atrophy may be one factor in the multiple mechanism
      underlying their institutional admission.

PMID- 16278190
TI  - Metabolism of [3H]pentosan polysulfate sodium (PPS) in healthy human volunteers.
AB  - Pentosan polysulfate sodium (PPS) is the active ingredient in ELMIRON, a drug
      approved for the relief of bladder pain associated with interstitial cystitis.
      The study objective was to characterize the pharmacokinetic and metabolic
      profiles of PPS following oral dosing of [3H]PPS. As specific assays for PPS do
      not exist, metabolic profiling was accomplished through multiple fraction
      collections and radiochromatographic techniques. Two groups of eight healthy
      female subjects sequentially received a single oral dose of 200 microCi [3H]PPS
      supplemented with 300 mg unlabelled PPS or 300 microCi [3H]PPS supplemented with
      450 mg unlabelled PPS. Most of the administered dose (84%) was excreted in faeces
      as intact PPS, and a smaller percentage (6%) was excreted in urine. In summary,
      orally administered PPS was very poorly absorbed, with the majority of the drug
      being excreted in faeces as intact PPS and in urine as low molecular weight and
      desulfated PPS.

PMID- 16278192
TI  - In vitro microsomal metabolic studies on a selective mGluR5 antagonist MTEP:
      characterization of in vitro metabolites and identification of a novel thiazole
      ring opening aldehyde metabolite.
AB  - In vitro liver microsomal studies revealed that [14C] MTEP (3-[2-methyl-1,3
      thiazol-4-yl)ethynyl] pyridine) was metabolized into three major oxidative
      metabolites. Metabolite 1 (M1) was shown to be a hydroxymethyl metabolite; M2 was
      shown to be a pyridine oxide. Moreover, a novel aldehyde metabolite (M3) was
      identified from mouse liver microsomes. The structure of the aldehyde M3 was
      elucidated by LC/MS/MS. In addition, methoxyamine, an aldehyde-trapping agent,
      and accurate mass measurement using a high-resolution quadrupole-time of flight
      (Q-TOF) instrument, were used to confirm the proposed thiazole ring-opening
      structure of M3. A mechanism for aldehyde M3 formation was postulated based on
      MTEP incubation studies with 18O2 and H2 18O using mouse liver microsomes. MTEP
      was initially oxidized at sulfur, followed by subsequent C4-C5 of thiazole
      epoxidation, thiozole ring opening and further oxidative desulfation. This
      proposed thiazole ring-opening mechanism might represent a novel metabolism
      pathway for xenobiotics containing a thiazole moiety. Species differences in the
      metabolism of MTEP were observed in mouse, rat, dog, monkey and human liver
      microsomes. Mouse appears to generate all three oxidative metabolites to a
      greater extent than other species examined.

PMID- 16278191
TI  - Ketobemidone is a substrate for cytochrome P4502C9 and 3A4, but not for P
      glycoprotein.
AB  - The role of the major drug-metabolizing cytochrome P450 (CYP) enzymes as well as
      P-glycoprotein (PGP) was investigated in the disposition of ketobemidone in
      vitro. Formation of norketobemidone from ketobemidone was studied and compared
      with the activities of 11 major CYP enzymes in human liver microsomes. The
      formation of norketobemidone from ketobemidone (1 microM) correlated best with
      CYP2C9 activity, measured as losartan oxidation (rs = 0.82, n = 19, p < 0.001),
      but there was also a strong correlation with CYP3A4 activity. Additionally, a
      good correlation was observed with CYP2C19, CYP2C8 and CYP2B6 at a ketobemidone
      concentration of 50 microM. Inhibition studies confirmed the involvement of
      CYP2C9 and CTP3A4 in the formation of norketobemidone. The formation rate of
      norketobemidone was three times higher in the CYP2C9*1*1 genotype group compared
      with the CYP2C9*1*2, CYP2C9*1*3 and CYP2C9*3*3 genotypes (p < 0.01). Treatment
      with verapamil as a PGP inhibitor did not affect the transport of ketobemidone in
      Caco-2 cells, indicating that PGP is not involved. The data suggest that CYP2C9
      and CYP3A4 play a major role in the formation of norketobemidone at clinically
      relevant concentrations.

PMID- 16278193
TI  - Identification and quantification of metabolites of arachidonic acid from
      cultures of endothelial cells by HPLC-MS2.
AB  - Epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs) are
      oxidative products of arachidonic acid, some of which participate in the
      regulation of vascular tone. Little is known about the production of EETs and
      HETEs in cultures of endothelial cells. This paper reports an assay for the
      simultaneous quantification of isomers of EETs and HETEs from endothelial cell
      culture supernatants by employing solid-phase extraction and liquid
      chromatography-mass spectrometry. The method enabled measurement of 5,6-EET, 8,9
      EET, 11,12-EET, 14,15-EET, 5-HETE, 8-HETE, 11-HETE, 12-HETE and 15-HETE. The
      metabolites were chromatographically separated by reversed-phase HPLC and
      identified by negative ESI tandem mass spectrometry and this method was used to
      investigate the metabolism of arachidonic acid with an endothelial cell line. For
      quantification, the sum of signal intensities of characteristic fragment ions was
      used. The detection limits for 5,6-EET and of other EET and HETE isomers were
      2.0, 0.64 and 8 ng ml(-1) culture medium, respectively. The precision of the
      method was determined with spiked culture medium (three concentrations, n = 5)
      and the average RSD ranged from 6.0 to 24.2%. The dynamic range was 0.6-23.5 ng
      ml(-1) culture medium for EETs and 8.0-200 ng ml(-1) for HETEs. Arachidonic acid
      was mainly metabolised to HETEs with product levels ranging from 59.3 to 460 ng
      10(-6) cells. The median of 8,9-EET and 14,15-EET was 14.5 and 17.7 ng 10(-6)
      cells, respectively, whereas 5,6-EET and 11,12-EET were below 2 ng 10(-6) cells
      in a 5-min incubation assay at a 30 microM arachidonic acid substrate
      concentration.

PMID- 16278194
TI  - Effect of 1-aminobenzotriazole on the in vitro metabolism and single-dose
      pharmacokinetics of chlorzoxazone, a selective CYP2E1 substrate in Wistar rats.
AB  - The aim of this study was to study the effect of 1-aminobenzotriazole (ABT) on in
      vitro metabolism, oral, and intravenous (IV) pharmacokinetics of chlorzoxazone
      (CZX) in rats. Enzyme kinetics of CZX was performed with rat and human liver
      microsomes and pure isozyme (CYP2E1) with and without ABT. The enzyme kinetics
      (V(max) and K(m)) of the formation of 6-hydroxychlorzoxazone (OH-CZX) was found
      to be similar among rat liver microsomes (3486 pmol mg protein(-1) min(-1) and
      345 microM), human liver microsomes (3194 pmol mg protein(-1) min(-1) and 335
      microM) and pure isozyme (3423 pmol mg protein(-1) min(-1) and 403 microM), but
      K(I) and K(inact) values for ABT towards the ability to inhibit the formation of
      OH-CZX from CZX varied between liver microsomes (rat: 32.09 microM and 0.12 min(
      1); human: 27.19 microM and 0.14 min(-1)) and pure isozyme (3.18 microM and 0.29
      min(-1)). The novel robust analytical method was capable of quantifying CZX, OH
      CZX, and ABT simultaneously in a single run, and the method was used for both in
      vitro and in vivo studies. Pre-treatment of rats with ABT prior to oral and IV
      administration of CZX significantly decreased the clearance (threefold) and
      consequently increased the AUC of CZX (approx. three- to fourfold). When rats
      were pre-treated with ABT, the formation of OH-CZX was completely blocked after
      oral and IV administration; however, we were able to measure OH-CZX in rats
      administered with CZX by oral and IV routes without pre-treatment of ABT. The
      oral bioavailability of CZX was approximately 71% when dosed alone and reached
      100% under pre-treatment with ABT. The t(1/2) values of CZX was significantly
      prolonged for oral dosing compared with IV dosing under pre-treated conditions
      with ABT, suggesting an involvement of pre-systemic component in the disposition
      of CZX. The pharmacokinetic parameters of ABT did not change when it was dosed
      along with CZX (oral and IV), indicating that either CZX or OH-CZX had no effect
      on disposition of ABT. The plasma concentrations of ABT were above and beyond the
      required levels to inhibit CYP2E1 enzyme for at least 36 h post-treatment.

PMID- 16278195
TI  - Chemometric analysis of biofluids following toxicant induced hepatotoxicity: a
      metabonomic approach to distinguish the effects of 1-naphthylisothiocyanate from
      its products.
AB  - Metabonomics using high-resolution 1H-NMR spectroscopy of biofluids and pattern
      recognition is highly successful at distinguishing both organ- and sub-organ
      specific toxicity. In the current study, this technique was investigated to
      distinguish the different biological effects caused by 1-naphthylisothiocyanate
      (ANIT)-induced hepatotoxicity in the rat from that induced by exposure to 1
      naphthylisocyanate (NI) and 1-naphthylamine (NA), two products of the metabolism
      of ANIT. While all three toxicants produced perturbations in similar urinary
      metabolites, principal components analysis of the temporal progression identified
      that the rapid initial glycosuria associated with ANIT toxicity was also present
      with NI but not NA dosing. However, longer-term perturbations in the urinary
      excretion of succinate, lactate and acetate were common to all three toxicants.
      The metabolic effects of the three compounds were also followed in blood plasma
      and liver tissue. Of the three toxicants, the most marked perturbations were
      induced by ANIT exposure, then NI, thereby indicating the effects of ANIT, NI and
      NA toxicity were distinct, with ANIT being the most, and NA the least, toxic of
      the three compounds. This indicates that metabonomics may be useful for following
      severity and mechanisms of toxicity in a series of related compounds during drug
      development.

PMID- 16278196
TI  - Advancing an agenda on risk and chronic disease.

PMID- 16278197
TI  - Portrayal of childhood cancer in English language magazines in North America:
      1970-2001.
AB  - This article is a content and discourse analysis of the portrayal of childhood
      cancer in English language magazines in North America. In a unique specification
      of published research on the media portrayal of disease, magazines were divided
      into three market or audience groupings called (1) science, (2) news/special
      interest, and (3) other (women/teen/parenting/health). The predominate frames or
      discoursesin these three groups were compared and differences were found amongst
      them and discussed in the article. Considerable evidence suggests that people
      with cancer are stigmatized. In the analyzed media focused on children, those
      with cancer are highly idealized and stereotyped. On the one hand, this can be
      thought of as a very positive portrayal of children in this situation. Children
      are described as if they possess heroic and idealized character traits,
      appearances, social characteristics, and personalities. Possible links between
      this idealized, polarized, and biased portrayal of children with cancer and their
      documented experiences of stigma are discussed.

PMID- 16278198
TI  - Comprehension of information in three direct-to-consumer television prescription
      drug advertisements among adults with limited literacy.
AB  - Direct-to-consumer (DTC) television advertisements present a number of facts
      about prescription drug risks and benefits in a brief time. This study assessed
      comprehension of information in three advertisements among 50 adults with limited
      literacy. Participants correctly answered an average of 59% of comprehension
      questions. The percentage of respondents correctly answering individual
      comprehension questions ranged from 26% to 92%. A multivariate analysis suggested
      that type of information (risk vs. other) and channel (text vs. audio) predicted
      comprehension. There was a significant interaction effect for literacy and place
      of birth. Our results suggest key areas for future research on comprehension of
      DTC advertising.

PMID- 16278199
TI  - Personal values, advertising, and smoking motivation in Taiwanese adolescents.
AB  - This article explores the role that personal values plays in motivating Taiwanese
      adolescents to smoke. In a nationwide survey of high school students, smokers
      attached greater importance to hedonic gratification values and less importance
      to idealism values than did nonsmokers. Hedonic gratification values were
      associated with favorable attitudes toward smoking, while idealism values were
      associated with unfavorable attitudes toward smoking. Attitudes toward smoking
      predicted adolescent smoking behavior. Evidence suggested that advertising plays
      an important role in motivating adolescents with hedonic gratification values to
      smoke. First, in the survey, hedonic gratification values were associated with
      paying attention to and expressing favorable attitudes toward cigarette
      advertising. Second, a content analysis of cigarette ads in magazines found
      hedonic gratification values to be the most commonly portrayed values, occurring
      in 62.7% of ads.

PMID- 16278200
TI  - Assessing the validity of confirmed AD recall measures for public health
      communication campaign evaluation.
AB  - Evidence strongly suggests that public health communication campaigns can succeed
      in changing health-related cognitions and behaviors. For many evaluation studies,
      however, inferences of campaign effects are only valid to the extent that
      measures of campaign exposure are themselves valid. This study compares the
      validity of "aided" and "confirmed" ad recall measures in the context of a
      statewide tobacco countermarketing campaign using data from the Florida Anti
      Tobacco Media Evaluation (FAME) surveys. Both aided and confirmed ad recall
      measures exhibited positive associations with cumulative gross ratings points
      (GRPs), a measure of the relative availability of specific countermarketing ads
      on broadcast television. In addition, both recall measures were significant
      predictors of campaign-targeted beliefs. Confirmed ad recall, however, was not a
      significantly better predictor of cumulative GRPs or campaign-targeted beliefs
      than aided ad recall, and the magnitude of association between both recall
      measures and targeted beliefs was quite small. These findings raise questions
      about the marginal utility of confirmed ad recall measures, compared with aided
      ad recall, in public health communication campaign evaluations. Nevertheless,
      results do provide evidence that both aided and confirmed ad recall measures are
      valid measures of campaign exposure.

PMID- 16278201
TI  - Literacy and knowledge, attitudes, and behavior about colorectal cancer
      screening.
AB  - This cross-sectional survey explored the association between functional health
      literacy and knowledge of, beliefs and attitudes about, and reported usage of
      colorectal cancer screening tests. The results indicate that functional health
      literacy, as assessed by the Short Test of Functional Health Literacy in Adults
      (STOFHLA), is not an independent predictor of colorectal cancer screening
      knowledge, beliefs, attitudes, or behavior. Latino ethnicity and education,
      however, often predicted screening responses, suggesting that efforts to improve
      communication about colorectal cancer screening with Latino patients and patients
      with low education clearly are needed to reduce the disparities in awareness and
      utilization of colorectal cancer screening tests. This study also explored
      influences on intended screening behavior. Physician recommendation was found to
      be a powerful motivator of intention to undergo colorectal cancer screening
      regardless of literacy level, indicating that interventions aimed at increasing
      physician recommendation of colorectal cancer screening may be an effective way
      of increasing screening rates.

PMID- 16278202
TI  - Combating syphilis and HIV among users of internet chatrooms.
AB  - The recent resurgence of syphilis among men-who-have-sex-with-men (MSM) and
      concerns about a potential increase in HIV incidence have sparked public health
      authorities to search for new approaches to address this converging problem.
      Epidemiologic investigations suggest that the Internet plays an important role in
      facilitating syphilis outbreaks. The experience of this pilot will help the
      public health community learn more about how to reach targeted online audiences,
      and will contribute toward understanding the role of the Internet in risk
      reduction strategies aimed at persons who use the Internet to meet sex partners.

PMID- 16278208
TI  - Cross-species vascular endothelial growth factor (VEGF)-blocking antibodies
      completely inhibit the growth of human tumor xenografts and measure the
      contribution of stromal VEGF.
AB  - To fully assess the role of VEGF-A in tumor angiogenesis, antibodies that can
      block all sources of vascular endothelial growth factor (VEGF) are desired.
      Selectively targeting tumor-derived VEGF overlooks the contribution of host
      stromal VEGF. Other strategies, such as targeting VEGF receptors directly or
      using receptor decoys, result in inhibiting not only VEGF-A but also VEGF
      homologues (e.g. placental growth factor, VEGF-B, and VEGF-C), which may play a
      role in angiogenesis. Here we report the identification of novel anti-VEGF
      antibodies, B20 and G6, from synthetic antibody phage libraries, which block both
      human and murine VEGF action in vitro. Their affinity-improved variants
      completely inhibit three human tumor xenografts in mice of skeletal muscle,
      colorectal, and pancreatic origins (A673, HM-7, and HPAC). Avastin, which only
      inhibits the tumor-derived human VEGF, is approximately 90% effective at
      inhibiting HM-7 and A673 growth but is <50% effective at inhibiting HPAC growth.
      Indeed, HPAC tumors contain more host stroma invasion and stroma-derived VEGF
      than other tumors. Thus, the functional contribution of stromal VEGF varies
      greatly among tumors, and systemic blockade of both tumor and stroma-derived VEGF
      is sufficient for inhibiting the growth of tumor xenografts.

PMID- 16278209
TI  - The [Fe-Fe]-hydrogenase maturation protein HydF from Thermotoga maritima is a
      GTPase with an iron-sulfur cluster.
AB  - The active site of [Fe-Fe]-hydrogenases is composed of a di-iron complex, where
      the two metal atoms are bridged together by a putative di(thiomethyl)amine
      molecule and are also ligated by di-nuclear ligands, namely carbon monoxide and
      cyanide. Biosynthesis of this metal site is thought to require specific protein
      machinery coded by the hydE, hydF, and hydG genes. The HydF protein has been
      cloned from the thermophilic organism Thermotoga maritima, purified, and
      characterized. The enzyme possesses specific amino acid signatures for GTP
      binding and is able to hydrolyze GTP. The anaerobically reconstituted TmHydF
      protein binds a [4Fe-4S] cluster with peculiar EPR characteristics: an S = 1/2
      signal presenting a high field shifted g-value together with a S = 3/2 signal,
      similar to those observed for [4Fe-4S] clusters ligated by only three cysteines.
      HYSCORE spectroscopy experiments were carried out to determine the nature of the
      fourth ligand of the cluster, and its exchangeability was demonstrated with the
      formation of a [4Fe-4S]-imidazole complex.

PMID- 16278210
TI  - Chemical blockage of the proteasome inhibitory function of bortezomib: impact on
      tumor cell death.
AB  - The proteasome inhibitor bortezomib is emerging as a potent anti-cancer agent.
      Still, recent clinical trials have revealed a significant secondary toxicity of
      bortezomib. Consequently, there is much interest in dissecting the mechanism of
      action of this compound to rationally improve its therapeutic index. The
      cytotoxic effect of bortezomib is frequently characterized by interfering with
      downstream events derived from the accumulation of proteasomal targets. Here we
      identify the first chemical agent able to act upstream of the proteasome to
      prevent cell killing by bortezomib. Specifically, we show that the polyhydroxyl
      compound Tiron can function as a competitive inhibitor of bortezomib. This effect
      of Tiron was surprising, since it is a classical radical spin trap and was
      expected to scavenge reactive oxygen species produced as a consequence of
      bortezomib action. The inhibitory effect of Tiron against bortezomib was
      selective, since it was not shared by other antioxidants, such as vitamin E,
      MnTBAP, L-N-acetyl-cysteine, and FK-506. Comparative analyses with nonboronated
      proteasome inhibitors (i.e. MG132) revealed a specificity of Tiron for
      bortezomib. We exploited this novel feature of Tiron to define the "point of no
      return" of proteasome inhibition in melanoma cells and to block cell death in a
      three-dimensional model of human skin. Cells from T-cell lymphoma, breast
      carcinoma, and non-small cell lung cancer were also responsive to Tiron,
      suggesting a broad impact of this agent as a bortezomib blocker. These results
      may have important implications for the analysis of bortezomib in vivo and for
      the design of drug mixtures containing proteasome inhibitors.

PMID- 16278211
TI  - Identification and characterization of a mammalian 39-kDa poly(ADP-ribose)
      glycohydrolase.
AB  - ADP-ribosylation is a post-translational modification resulting from transfer of
      the ADP-ribose moiety of NAD to protein. Mammalian cells contain mono-ADP
      ribosyltransferases that catalyze the formation of ADP-ribose-(arginine) protein,
      which can be cleaved by a 39-kDa ADP-ribose-(arginine) protein hydrolase (ARH1),
      resulting in release of free ADP-ribose and regeneration of unmodified protein.
      Enzymes involved in poly(ADP-ribosylation) participate in several critical
      physiological processes, including DNA repair, cellular differentiation, and
      carcinogenesis. Multiple poly(ADP-ribose) polymerases have been identified in the
      human genome, but there is only one known poly(ADP-ribose) glycohydrolase (PARG),
      a 111-kDa protein that degrades the (ADP-ribose) polymer to ADP-ribose. We report
      here the identification of an ARH1-like protein, termed poly(ADP-ribose)
      hydrolase or ARH3, which exhibited PARG activity, generating ADP-ribose from poly
      (ADP-ribose), but did not hydrolyze ADP-ribose-arginine, -cysteine, -diphthamide,
      or -asparagine bonds. The 39-kDa ARH3 shares amino acid sequence identity with
      both ARH1 and the catalytic domain of PARG. ARH3 activity, like that of ARH1, was
      enhanced by Mg(2+). Critical vicinal acidic amino acids in ARH3, identified by
      mutagenesis (Asp(77) and Asp(78)), are located in a region similar to that
      required for activity in ARH1 but different from the location of the critical
      vicinal glutamates in the PARG catalytic site. All findings are consistent with
      the conclusion that ARH3 has PARG activity but is structurally unrelated to PARG.

PMID- 16278212
TI  - Y-box protein-1 is the crucial mediator of antifibrotic interferon-gamma effects.
AB  - Y-box protein-1 (YB-1) is a known negative regulator of collagen (Col) expression
      by two different mechanisms, acting directly through binding to an interferon
      gamma response element within the col1A2 promoter and/or by physically
      interacting with p300/Smad3, thereby abrogating the stimulatory effect of
      transforming growth factor-beta (TGF-beta). Here, we report that YB-1 activation
      via the Jak1 signaling pathway is required and sufficient to confer interferon
      gamma-dependent activation of the smad7 gene. By binding to a bona fide
      recognition site within the smad7 promoter, YB-1 up-regulates smad7
      transcription, which was additively enhanced by autoinhibitory TGF-beta
      signaling. Importantly, the anti-TGF-beta effect was not only supplied by induced
      Smad7 expression but was recapitulated in the context of the col1A2 promoter,
      where YB-1 overexpression abolished the trans-stimulatory TGF-beta effect in a
      dominant fashion. In conclusion, YB-1 is the main target of interferon-gamma
      signaling via Jak1 that exerts antifibrotic action by both interference with TGF
      beta signaling and direct down-regulation of collagen expression.

PMID- 16278213
TI  - The physical properties of the capsular polysaccharides from Cryptococcus
      neoformans suggest features for capsule construction.
AB  - The most distinctive feature of the human pathogenic fungus is a polysaccharide
      capsule that is essential for virulence and is composed primarily of
      glucuronoxylomannan (GXM) and galactoxylomannan (GalXM). GXM mediates multiple
      deleterious effects on host immune function, yet relatively little is known about
      its physical properties. The average mass of Cryptococcus neoformans GXM from
      four antigenically different strains ranged from 1.7 to 7 x 10(6) daltons as
      calculated from Zimm plots of light-scattering data. GalXM was significantly
      smaller than GXM, with an average mass of 1 x 10(5) daltons. These molecular
      masses imply that GalXM is the most numerous polysaccharide in the capsule on a
      molar basis. The radius of gyration of the capsular polysaccharides ranged
      between 68 and 208 nm. Viscosity measurements suggest that neither polysaccharide
      altered fluid dynamics during infection since GXM behaved in solution as a
      polyelectrolyte and GalXM did not increase solution viscosity. Immunoblot
      analysis indicated heterogeneity within GXM. In agreement with this, scanning
      transmission electron microscopy of GXM preparations revealed a tangled network
      of two different types of molecules. Mass per length measurements from light
      scattering and scanning transmission electron microscopy were consistent and
      suggested GXM molecules self-associate. A mechanism for capsule growth is
      proposed based on the extracellular release and entanglement of GXM molecules.

PMID- 16278215
TI  - RhoB protects human keratinocytes from UVB-induced apoptosis through epidermal
      growth factor receptor signaling.
AB  - Exposure of the skin to UVB light results in the formation of DNA photolesions
      that can give rise to cell death, mutations, and the onset of carcinogenic
      events. Specific proteins are activated by UVB and then trigger signal
      transduction pathways that lead to cellular responses. An alteration of these
      signaling molecules is thought to be a fundamental event in tumor promotion by
      UVB irradiation. RhoB, encoding a small GTPase has been identified as a DNA
      damage-inducible gene. RhoB is involved in epidermal growth factor (EGF) receptor
      trafficking, cytoskeletal organization, cell transformation, and survival. We
      have analyzed the regulation of RhoB and elucidated its role in the cellular
      response of HaCaT keratinocytes to relevant environmental UVB irradiation. We
      report here that the activated GTP-bound form of RhoB is increased rapidly within
      5 min of exposure to UVB, and then RhoB protein levels increased concomitantly
      with EGF receptor (EGFR) activation. Inhibition of UVB-induced EGFR activation
      prevents RhoB protein expression and AKT phosphorylation but not the early
      activation of RhoB. Blocking UVB-induced RhoB expression with specific small
      interfering RNAs inhibits AKT and glycogen synthase kinase-3beta phosphorylation
      through inhibition of EGFR expression. Moreover, down-regulation of RhoB
      potentiates UVB-induced cell apoptosis. In contrast, RhoB overexpression protects
      keratinocytes against UVB-induced apoptosis. These results indicated that RhoB is
      regulated upon UVB exposure by a two-step process consisting of an early EGFR
      independent RhoB activation followed by an EGFR-dependent induction of RhoB
      expression. Moreover, we have demonstrated that RhoB is essential in regulating
      keratinocyte cell survival after UVB exposure, suggesting its potential role in
      photocarcinogenesis.

PMID- 16278216
TI  - Polycystin-2 regulates proliferation and branching morphogenesis in kidney
      epithelial cells.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the
      formation of multiple fluid-filled cysts that expand over time and destroy the
      renal architecture. Loss or mutation of polycystin-1 or polycystin-2, the
      respective proteins encoded by the ADPKD genes PKD1 and PKD2, is associated with
      most cases of ADPKD. Thus, the polycystin proteins likely play a role in cell
      proliferation and morphogenesis. Recent studies indicate that polycystin-1 is
      involved in these processes, but little is known about the role played by
      polycystin-2. To address this question, we created a number of related cell lines
      variable in their expression of polycystin-2. We show that the basal and
      epidermal growth factor-stimulated rate of cell proliferation is higher in cells
      that do not express polycystin-2 versus those that do, indicating that polycystin
      2 acts as a negative regulator of cell growth. In addition, cells not expressing
      polycystin-2 exhibit significantly more branching morphogenesis and multicellular
      tubule formation under basal and hepatocyte growth factor-stimulated conditions
      than their polycystin-2-expressing counterparts, suggesting that polycystin-2 may
      also play an important role in the regulation of tubulogenesis. Cells expressing
      a channel mutant of polycystin-2 proliferated faster than those expressing the
      wild-type protein, but exhibited blunted tubule formation. Thus, the channel
      activity of polycystin-2 may be an important component of its regulatory
      machinery. Finally, we show that polycystin-2 regulation of cell proliferation
      appears to be dependent on its ability to prevent phosphorylated extracellular
      related kinase from entering the nucleus. Our results indicate that polycystin-2
      is necessary for the proper growth and differentiation of kidney epithelial cells
      and suggest a possible mechanism for the cyst formation seen in ADPKD2.

PMID- 16278217
TI  - Streptococcal protein FOG, a novel matrix adhesin interacting with collagen I in
      vivo.
AB  - Group G streptococcus (GGS) is a human pathogen of emerging clinical
      significance. It causes skin and soft tissue infections, occasionally resulting
      in life-threatening conditions such as sepsis and necrotizing fasciitis. We
      recently identified FOG, a novel surface protein of GGS with fibrinogen binding
      and immune evasion properties. Here we investigated the role of FOG in
      streptococcal primary adhesion to host tissue. A FOG-expressing clinical isolate
      adhered more efficiently to human skin biopsies ex vivo and to the murine dermis
      in vivo than a FOG-deficient strain. Scanning and transmission electron
      microscopy of skin specimens exhibited that this property was assigned to the
      ability of FOG to interact with collagen I, a major interstitial component of the
      dermis. Overlay experiments with human skin extracts and radiolabeled FOG
      followed by matrix-assisted laser desorption/ionization time of flight mass
      spectrometry analysis identified both the alpha1- and alpha2-chains of collagen I
      as targets for FOG. Transmission electron microscopy of the molecular complexes
      revealed thread-like FOG molecules binding via their NH2 termini to distinct
      sites on collagen I monomers and fibrils. The results demonstrate that FOG is
      important for GGS adhesion in vivo, implying a pathogenic role for this surface
      protein.

PMID- 16278218
TI  - Phosphorylation of HSF1 by MAPK-activated protein kinase 2 on serine 121,
      inhibits transcriptional activity and promotes HSP90 binding.
AB  - Heat shock transcription factor 1 (HSF1) monitors the structural integrity of
      intracellular proteins and its regulation is essential for the health and
      longevity of eukaryotic organisms. HSF1 also plays a role in the acute
      inflammatory response in the negative regulation of cytokine gene transcription.
      Here we show, for the first time, that HSF1 is regulated by the proinflammatory
      protein kinase MAPKAP kinase 2 (MK2). We have shown that MK2 directly
      phosphorylates HSF1 and inhibits activity by decreasing its ability to bind the
      heat shock elements (HSE) found in the promoters of target genes encoding the HSP
      molecular chaperones and cytokine genes. We show that activation of HSF1 to bind
      HSE in hsp promoters is inhibited through the phosphorylation of a specific
      residue, serine 121 by MK2. A potential mechanism for MK2-induced HSF1
      inactivation is suggested by the findings that phosphorylation of serine 121
      enhances HSF1 binding to HSP90, a major repressor of HSF1. Dephosphorylation of
      serine 121 in cells exposed to non-steroidal anti-inflammatory drugs leads to
      HSP90 dissociation from HSF1, which then forms active DNA binding trimers. These
      experiments indicate a novel mechanism for the regulation of HSF1 by
      proinflammatory signaling and may permit HSF1 to respond rapidly to extracellular
      events, permitting optimal physiological regulation.

PMID- 16278219
TI  - Hydrolysis of phosphatidylserine-exposing red blood cells by secretory
      phospholipase A2 generates lysophosphatidic acid and results in vascular
      dysfunction.
AB  - Secretory phospholipase A(2) (sPLA(2)) type IIa, elevated in inflammation, breaks
      down membrane phospholipids and generates arachidonic acid. We hypothesized that
      sPLA(2) will hydrolyze red blood cells that expose phosphatidylserine (PS) and
      generate lysophosphatidic acid (LPA) from phosphatidic acid that is elevated in
      PS-exposing red blood cells. In turn, LPA, a powerful lipid mediator, could
      affect vascular endothelial cell function. Although normal red blood cells were
      not affected by sPLA(2), at levels of sPLA(2) observed under inflammatory
      conditions (100 ng/ml) PS-exposing red blood cells hemolyzed and generated LPA
      (1.2 nM/10(8) RBC). When endothelial cell monolayers were incubated in vitro with
      LPA, a loss of confluence was noted. Moreover, a dose-dependent increase in
      hydraulic conductivity was identified in rat mesenteric venules in vivo with 5
      microM LPA, and the combination of PS-exposing red blood cells with PLA(2) caused
      a similar increase in permeability. In the presence of N-palmitoyl L-serine
      phosphoric acid, a competitive inhibitor for the endothelial LPA receptor, loss
      of confluence in vitro and the hydraulic permeability caused by 5 microM LPA in
      vivo were abolished. The present study demonstrates that increased sPLA(2)
      activity in inflammation in the presence of cells that have lost their membrane
      phospholipid asymmetry can lead to LPA-mediated endothelial dysfunction and loss
      of vascular integrity.

PMID- 16278214
TI  - The cis-regulatory element Gsl5 is indispensable for proximal straight tubule
      cell-specific transcription of core 2 beta-1,6-N-acetylglucosaminyltransferase in
      the mouse kidney.
AB  - Gsl5 regulates the expression of a glycolipid and glycoproteins that contain the
      Le(X) epitope in the mouse kidney through tissue-specific transcriptional
      regulation of the core 2 beta-1,6-N-acetylglucosaminyltransferase (core 2 GnT)
      gene. The core 2 GnT gene has six exons and produces three alternatively spliced
      transcripts. Gsl5 regulates only the expression of the kidney-type mRNA, which is
      transcribed from the most 5'-upstream exon. By introducing a 159-kb bacterial
      artificial chromosome (BAC) clone that carries the mouse core 2 GnT gene and its
      5'-upstream region into DBA/2 mice that carry a defective Gsl5 allele, we were
      able to rescue the deficient phenotype. The BAC clone was subsequently engineered
      to replace the core 2 GnT gene with the sequence of enhanced green fluorescent
      protein (EGFP) as a reporter by an inducible homologous recombination system in
      Escherichia coli. The transgenic mice derived from the modified BAC clone
      expressed EGFP in the kidney, which suggests that the candidate Gsl5 is in the 5'
      upstream region of the core 2 GnT gene. Sequence analysis of the 5'-upstream
      regions of the BAC clone and DBA/2 genomic DNA revealed a candidate sequence for
      Gsl5 at about 5.5 kb upstream of exon 1. This sequence consisted of eight repeats
      of two GT-rich units in the wild-type mice, whereas it consisted of only one pair
      of GT-rich units with a minor modification in the DBA/2 mice. Transgenic mice
      produced with the EGFP reporter gene construct that included this candidate
      sequence expressed EGFP exclusively in the proximal straight tubular cells of the
      kidney. These results indicated that this unique repeat is indeed the Gsl5, and
      it is a cis-regulatory element responsible for proximal straight tubule cell
      specific transcriptional regulation.

PMID- 16278220
TI  - Model of biologically active apolipoprotein E bound to
      dipalmitoylphosphatidylcholine.
AB  - Apolipoprotein (apo)E plays a critical role in cholesterol transport, through
      high affinity binding to the low density lipoprotein receptor. This interaction
      requires apoE to be associated with a lipoprotein particle. To determine the
      structure of biologically active apoE on a lipoprotein particle, we crystallized
      dipalmitoylphosphatidylcholine particles containing two apoE molecules and
      determined the molecular envelope of apoE at 10 Angstroms resolution. On the
      basis of the molecular envelope and supporting biochemical evidence, we propose a
      model in which each apoE molecule is folded into a helical hairpin with the
      binding region for the low density lipoprotein receptor at its apex.

PMID- 16278221
TI  - Characterization of an aldolase-binding site in the Wiskott-Aldrich syndrome
      protein.
AB  - The thrombospondin-related anonymous protein (TRAP) is an essential transmembrane
      molecule in Plasmodium sporozoites. TRAP displays adhesive motifs on the
      extracellular portion, whereas its cytoplasmic tail connects to actin via
      aldolase, thus driving parasite motility and host cell invasion. The minimal
      requirements for the TRAP binding to aldolase were scanned here and found to be
      shared by different human proteins, including the Wiskott-Aldrich syndrome
      protein (WASp) family members. In vitro and in vivo binding of WASp members to
      aldolase was characterized by biochemical, deletion mapping, mutagenesis, and co
      immunoprecipitation studies. As in the case of TRAP, the binding of WASp to
      aldolase is competitively inhibited by the enzyme substrate/products.
      Furthermore, TRAP and WASp, but not other unrelated aldolase binders, compete for
      the binding to the enzyme in vitro. Together, our results define a conserved
      aldolase binding motif in the WASp family members and suggest that aldolase
      modulates the motility and actin dynamics of mammalian cells. These findings
      along with the presence of similar aldolase binding motifs in additional human
      proteins, some of which indeed interact with aldolase in pull-down assays,
      suggest supplementary, non-glycolytic roles for this enzyme.

PMID- 16278222
TI  - Expression profiling identifies genes expressed early during lint fibre
      initiation in cotton.
AB  - Cotton fibres are a subset of single epidermal cells that elongate from the seed
      coat to produce the long cellulose strands or lint used for spinning into yarn.
      To identify genes that might regulate lint fibre initiation, expression profiles
      of 0 days post-anthesis (dpa) whole ovules from six reduced fibre or fibreless
      mutants were compared with wild-type linted cotton using cDNA microarrays.
      Numerous clones were differentially expressed, but when only those genes that are
      normally expressed in the ovule outer integument (where fibres develop) were
      considered, just 13 different cDNA clones were down-regulated in some or all of
      the mutants. These included: a Myb transcription factor (GhMyb25) similar to the
      Antirrhinum Myb AmMIXTA, a putative homeodomain protein (related to Arabidopsis
      ATML1), a cyclin D gene, some previously identified fibre-expressed structural
      and metabolic genes, such as lipid transfer protein, alpha-expansin and sucrose
      synthase, as well as some unknown genes. Laser capture microdissection and
      reverse transcription-PCR were used to show that both the GhMyb25 and the
      homeodomain gene were predominantly ovule specific and were up-regulated on the
      day of anthesis in fibre initials relative to adjacent non-fibre ovule epidermal
      cells. Their spatial and temporal expression pattern therefore coincided with the
      time and location of fibre initiation. Constitutive overexpression of GhMyb25 in
      transgenic tobacco resulted in an increase in branched long-stalked leaf
      trichomes. The involvement of cell cycle genes prompted DNA content measurements
      that indicated that fibre initials, like leaf trichomes, undergo DNA
      endoreduplication. Cotton fibre initiation therefore has some parallels with leaf
      trichome development, although the detailed molecular mechanisms are clearly
      different.

PMID- 16278223
TI  - Intraoperative electrophysiological confirmation of neurovascular bundle
      preservation during radical prostatectomy: long-term assessment of urinary and
      sexual function.
AB  - OBJECTIVE: We investigated the longitudinal recovery of urinary and sexual
      function after radical retropubic prostatectomy (RP) using an intraoperative
      electrophysiological test to confirm the functional preservation of the
      neurovascular bundle (NVB). METHODS: A total of 70 patients who underwent RP for
      localized prostate cancer were prospectively enrolled in our survey. During RP,
      electrophysiological testing was performed to confirm the NVB preservation. The
      NVB was electrostimulated and the responses were observed by monitoring the
      intracavernous or intraurethral pressure changes. All patients were classified
      into three groups according to the degree of nerve-sparing [a bilateral nerve
      sparing group (BNS), a unilateral nerve-sparing group (UNS) and a non-nerve
      sparing group (NNS)] based on the macroanatomical as well as the
      electrophysiological assessment. Both urinary and sexual function were measured
      before and 3, 6, 12 and 24 months after RP by a self-administered questionnaire.
      RESULTS: The concordance rate of nerve-sparing or non-nerve-sparing between the
      electrophysiological and macroanatomical assessment was 80%. According to the
      electrophysiological data, the BNS maintained significantly better urinary
      function at 3 months after RP than the NNS and UNS. After 6 months, each group
      had almost recovered continence. When considering sexual function, the BNS showed
      better sexual function scores than the NNS throughout the post-operative periods
      and the UNS at 2 years. According to the macroanatomical assessment, however,
      these differences were significant. CONCLUSIONS: Nerve-sparing RP as confirmed by
      intraoperative electrophysiological test may contribute significantly to the
      early recovery of continence and greater rate of sexual function after RP.

PMID- 16278224
TI  - A flexible endoscopic surgical system: first report on a conceptual design of the
      system validated by experiments.
AB  - BACKGROUND: Surgery is a standard diagnostic and therapeutic procedure. However,
      its technical difficulty and invasiveness pose problems that are yet to be solved
      even by current surgical robots. Flexible endoscopes can access regions deep
      inside the body with less invasiveness than surgical approaches. Conceptually,
      this ability can be a solution to some of the surgical problems. METHODS: A
      flexible (surgical) endoscopic surgical system was developed consisting of an
      outer and two inner endoscopes introduced through two larger working channels of
      the outer endoscope. The concept of the system as a surgical instrument was
      assessed by animal experiments. RESULTS: Gastric mucosa of the swine could be
      successfully resected using the flexible endoscopic surgical system, thereby
      showing us the prospect and directions for further development of the system.
      CONCLUSION: The concept of a flexible endoscopic surgical system is considered to
      offer some solutions for problems in surgery.

PMID- 16278225
TI  - The reliability and validity of the Index of Complexity, Outcome and Need for
      determining treatment need in Dutch orthodontic practice.
AB  - The Index of Complexity, Outcome and Need (ICON), based on international opinion,
      has been proposed as a multipurpose occlusal index. The aim of this study was to
      validate the ICON for treatment need in the Netherlands by relating it to Dutch
      orthodontic opinion. Furthermore, the reliability of this index was explored, for
      both a calibrated orthodontist and non-calibrated orthodontists. A sample of 102
      patients was chosen which represented the actual distribution of severity of
      malocclusion experienced by orthodontists in every day practice. The ICON was
      scored, based on complete patients records of those 102 patients, by an examiner
      calibrated in the use of this index. The results were compared with the opinion
      about treatment need of seven Dutch orthodontists - the 'gold standard'. Nine non
      calibrated orthodontists also scored the ICON for 49 patients. The intra-examiner
      agreement of both the non-calibrated and the calibrated orthodontists was
      moderate to high [0.52-0.86 and 0.89, respectively, measured with the Intraclass
      Correlation Coefficient (ICC)]. The inter-examiner agreement of the ICON score of
      the nine orthodontists was moderate measured with the single estimate of the ICC
      (0.60), and high measured with the average estimate (0.93). Spearman's
      correlation coefficient between the ICON score (calibrated) and the gold standard
      was sufficient: 0.78. The sensitivity and specificity were 1 and 0.36,
      respectively. The best compromise between sensitivity and specificity was at a
      cut-off point of 52, instead of the international ICON cut-off point of 43. There
      was a significant difference in ICON score between the non-calibrated
      orthodontists and the calibrated orthodontist, mainly based on the Aesthetic
      Component (AC) of the Index of Orthodontic Treatment Need (IOTN). It can be
      concluded that the ICON needs to be adjusted when used to determine treatment
      need in the Dutch orthodontic population.

PMID- 16278226
TI  - Developmental changes in craniofacial morphology in subjects with Duchenne
      muscular dystrophy.
AB  - Lateral cephalometric radiographs of 35 Japanese male patients suffering from
      Duchenne muscular dystrophy (DMD) were taken longitudinally from 10 to 20 years
      of age. Eighteen landmarks were placed and 15 angles and four linear distances
      calculated. Profile diagrams (profilograms) were produced to analyse changes in
      craniofacial morphological growth in the DMD subjects. The measurements were then
      compared with Japanese standards. In young patients with DMD, compared with the
      controls, the following were observed: a large gonial angle; clockwise rotation
      of the mandible; short sagittal length of the cranial base and protrusion of the
      upper incisors. In adult patients, the maxillary alveolus and the upper incisors
      were protruded, compared with the controls. Overbite in DMD subjects also showed
      a tendency to decrease. In the controls, mandibular growth direction tended to be
      straight down and forward, while in patients with DMD, the growth direction was
      down until approximately 16 years of age and, after that, a forward vector of
      growth was apparent. As a result, the tendency towards a clockwise rotation of
      the mandible in the adults was less than in the young patients. These findings
      showed that DMD significantly affects craniofacial morphology.

PMID- 16278227
TI  - Ankle brachial index, C-reactive protein, and central augmentation index to
      identify individuals with severe atherosclerosis.
AB  - OBJECTIVES: We examined the ability of ankle brachial index, C-reactive protein
      and central augmentation index to identify individuals in the general population
      with severe atherosclerosis, diagnosed as those with ischaemic cardiovascular
      disease. METHODS AND RESULTS: We examined 4159 randomly sampled individuals from
      the Danish general population, of which 250 had severe atherosclerosis. After
      adjustment for gender and age, individuals with ankle brachial index of 0.71-0.90
      and <0.70 vs. 0.91-1.10 had odds ratios for severe atherosclerosis of 1.6
      (95%CI:1.1-2.3) and 2.9 (1.9-4.6), respectively. C-reactive protein of >3.0 or
      1.0-3.0 mg/L vs. <1.0 mg/L as well as central augmentation index in quintiles did
      not identify individuals with severe atherosclerosis, and did not improve further
      the ability of ankle brachial index to identify such individuals. On a continuous
      scale using receiver operating characteristics curves, presence of severe
      atherosclerosis was predicted by ankle brachial index (P=0.00000003), C-reactive
      protein (P=0.000003), as well as central augmentation index (P=0.001); these
      three curves did not differ. CONCLUSION: Ankle brachial index <0.9 identify
      individuals with severe atherosclerosis in the general population, while C
      reactive protein in three groups and central augmentation index in quintiles did
      not. On a continuous scale, all three variables predicted severe atherosclerosis.

PMID- 16278228
TI  - Are tirofiban and abciximab identical in efficacy?

PMID- 16278229
TI  - Reduced apelin levels in lone atrial fibrillation.
AB  - AIMS: Apelin is an endogenous peptide hormone that appears to have a
      physiological role in counter-regulation of the angiotensin and vasopressin
      systems. This peptide has been reported to be down-regulated in subjects with
      acute heart failure, but has not been studied in other cardiovascular conditions.
      We studied apelin levels in 73 subjects with lone atrial fibrillation (AF).
      METHODS AND RESULTS: Study subjects had electrocardiographic evidence of
      paroxysmal or chronic AF and a structurally normal heart on echocardiography.
      Subjects were excluded if they had a history of coronary artery disease,
      rheumatic heart disease, cardiomyopathy, significant valvular disease,
      hyperthyroidism, or antecedent hypertension. Controls were recruited from a
      healthy outpatient population. Plasma apelin levels were determined using a
      commercially available immunoassay. Seventy-three subjects with lone AF and 73
      healthy controls were enrolled and studied. Mean levels of apelin were
      significantly lower in subjects with lone AF when compared with controls (307 vs.
      648 pg/mL, P<0.00005). CONCLUSION: Reduced apelin levels were observed in this
      homogenous population of lone AF subjects and may represent an underlying
      diathesis predisposing to this common arrhythmia.

PMID- 16278230
TI  - Is atrial fibrillation an inflammatory disorder?
AB  - There is mounting evidence to support the influence of inflammation in the
      pathogenesis of atrial fibrillation (AF). Indeed, AF is associated with increased
      levels of known inflammatory markers, even after adjustment for confounding
      factors. The renin-angiotensin-aldosterone system (RAAS) appears to play a key
      role in this process. Atrial biopsies from patients with AF have also confirmed
      the presence of inflammation. Furthermore, there is preliminary evidence to
      support a number of drug therapies that have the potential to reduce the clinical
      burden of AF. In this review, we present an overview of the evidence supporting a
      link between inflammation and AF, and some of the drug therapies, such as the
      angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers,
      steroids, fish oils, and vitamin C, that might be efficacious in the prevention
      of AF by modulating inflammatory pathways.

PMID- 16278231
TI  - Coronary endothelial dysfunction following sirolimus-eluting stent placement:
      should we worry about it?

PMID- 16278232
TI  - Dazl binds in vivo to specific transcripts and can regulate the pre-meiotic
      translation of Mvh in germ cells.
AB  - Gametogenesis is a complex process subject to strict controls at both levels of
      transcription and translation. Members of a family of conserved RNA-binding
      proteins encoded by the DAZ genes are required for the translational regulation
      of gene expression essential for this process. Although loss of DAZ family genes
      is associated with infertility in several organisms including humans, the
      identity of the transcripts regulated in vivo is unknown. Using a combination of
      immunoprecipitation and microarray analysis, we have identified a number of mRNAs
      that are bound by the murine Dazl protein both in vivo and in vitro. Sequence
      analysis shows that these transcripts contain binding sites for Dazl, which have
      been conserved during evolution between human, rat and mouse. We have focussed on
      mouse vasa homologue (Mvh), a gene that is essential for male gametogenesis, and
      show that Dazl stimulates translation via the Mvh 3'-UTR. Finally, we show that
      germ cells of Dazl null mice contain reduced levels of Mvh protein, indicating
      that Dazl-mediated regulation of Mvh translation is crucial for mammalian
      spermatogenesis.

PMID- 16278233
TI  - Stress-induced alterations in parkin solubility promote parkin aggregation and
      compromise parkin's protective function.
AB  - Mutations in parkin are currently recognized as the most common cause of familial
      Parkinsonism. Emerging evidence also suggests that parkin expression variability
      may confer a risk for the development of the more common, sporadic form of
      Parkinson's disease (PD). Supporting this, we have recently demonstrated that
      parkin solubility in the human brain becomes altered with age. As parkin
      apparently functions as a broad-spectrum neuroprotectant, the resulting decrease
      in the availability of soluble parkin with age may underlie the progressive
      susceptibility of the brain to stress. Interestingly, we also observed that many
      familial-PD mutations of parkin alter its solubility in a manner that is highly
      reminiscent of our observations with the aged brain. The converging effects on
      parkin brought about by aging and PD-causing mutations are probably not trivial
      and suggest that environmental modulators affecting parkin solubility would
      increase an individual's risk of developing PD. Using both cell culture and in
      vivo models, we demonstrate here that several PD-linked stressors, including
      neurotoxins (MPP+, rotenone, 6-hydroxydopamine), paraquat, NO, dopamine and iron,
      induce alterations in parkin solubility and result in its intracellular
      aggregation. Furthermore, the depletion of soluble, functional forms of parkin is
      associated with reduced proteasomal activities and increased cell death. Our
      results suggest that exogenously introduced stress as well as endogenous dopamine
      could affect the native structure of parkin, promote its misfolding, and
      concomitantly compromise its protective functions. Mechanistically, our results
      provide a link between the influence of environmental and intrinsic factors and
      genetic susceptibilities in PD pathogenesis.

PMID- 16278234
TI  - A loss of genome buffering capacity of Dahl salt-sensitive model to modulate
      blood pressure as a cause of hypertension.
AB  - Essential hypertension is a complex trait influenced by multiple genes known as
      quantitative trait loci (QTLs) for blood pressure (BP). It is not clear, however,
      what roles these QTLs play in maintaining normotension. Insights gained toward
      the maintenance of normotension will shed light on how hypertension can result
      from a deficiency or malfunctioning of this maintenance. Currently, congenic
      strains were systematically constructed using Dahl salt-sensitive (DSS) and Lewis
      (LEW) rats not only to define QTLs (i.e. in DSS background), but also to
      ascertain effects of the same QTLs in preserving normotension (i.e. in LEW
      background), a first such study. Results showed that although LEW alleles for two
      QTLs on Chromosome (Chr) 18 lowered BP on the DSS background, their BP-increasing
      DSS alleles failed to influence BP in the LEW background. To further prove that
      the LEW background is resistant and the DSS background is susceptible to the
      effects of QTLs, BP-increasing alleles of a QTL on Chr 2 were introgressed into
      the DSS background, and its BP-decreasing alleles into the LEW background.
      Indeed, there was no BP-decreasing effect on the LEW background while
      demonstrating a BP-increasing effect on the DSS background. Thus, a genetic
      regulation of BP QTLs in the LEW genome inhibits BP changes by nullifying the
      effects of BP-altering QTLs. In comparison, the DSS genome must have lost the
      buffering capacity for stabilizing BP. The current work presents good evidence
      that a lack of regulation for functions of BP QTLs is a potential underlying
      cause of hypertension.

PMID- 16278235
TI  - Targeted disruption of hepatic frataxin expression causes impaired mitochondrial
      function, decreased life span and tumor growth in mice.
AB  - We have disrupted expression of the mitochondrial Friedreich ataxia protein
      frataxin specifically in murine hepatocytes to generate mice with impaired
      mitochondrial function and decreased oxidative phosphorylation. These animals
      have a reduced life span and develop multiple hepatic tumors. Livers also show
      increased oxidative stress, impaired respiration and reduced ATP levels
      paralleled by reduced activity of iron-sulfur cluster (Fe/S) containing proteins
      (ISP), which all leads to increased hepatocyte turnover by promoting both
      apoptosis and proliferation. Accordingly, phosphorylation of the stress-inducible
      p38 MAP kinase was found to be specifically impaired following disruption of
      frataxin. Taken together, these findings indicate that frataxin may act as a
      mitochondrial tumor suppressor protein in mammals.

PMID- 16278236
TI  - Selective degeneration and nuclear localization of mutant huntingtin in the
      YAC128 mouse model of Huntington disease.
AB  - Huntington disease (HD) is an adult onset neurodegenerative disorder that
      predominantly affects the striatum and cortex despite ubiquitous expression of
      mutant huntingtin (htt). Here we demonstrate that this pattern of selective
      degeneration is present in the YAC128 mouse model of HD. At 12 months, YAC128
      mice show significant atrophy in the striatum, globus pallidus and cortex with
      relative sparing of the hippocampus and cerebellum (striatum: -10.4%, P<0.001;
      globus pallidus: -10.8%, P=0.04; cortex: -8.6%, P=0.001; hippocampus: +0.3%,
      P=0.9; cerebellum: +2.9%, P=0.6). Similarly, neuronal loss at this age is present
      in the striatum (-9.1%, P<0.001) and cortex of YAC128 mice (-8.3%, P=0.02) but is
      not detected in the hippocampus (+1.5%, P=0.72). Mutant htt expression levels are
      similar throughout the brain and fail to explain the selective neuronal
      degeneration. In contrast, nuclear detection of mutant htt occurs earliest and to
      the greatest extent in the striatum-the region most affected in HD. The
      appearance of EM48-reactive mutant htt in the nucleus in the striatum at 2 months
      coincides with the onset of behavioral abnormalities in YAC128 mice. In contrast
      to YAC128 mice, the R6/1 mouse model of HD, which expresses exon 1 of mutant htt,
      exhibits non-selective, widespread atrophy along with non-selective nuclear
      detection of mutant htt at 10 months of age. Our findings suggest that selective
      nuclear localization of mutant htt may contribute to the selective degeneration
      in HD and that appropriately regulated expression of full-length mutant htt in
      YAC128 mice results in a pattern of degeneration remarkably similar to human HD.

PMID- 16278237
TI  - Prediction of functional specificity determinants from protein sequences using
      log-likelihood ratios.
AB  - MOTIVATION: A number of methods have been developed to predict functional
      specificity determinants in protein families based on sequence information. Most
      of these methods rely on pre-defined functional subgroups. Manual subgroup
      definition is difficult because of the limited number of experimentally
      characterized subfamilies with differing specificity, while automatic subgroup
      partitioning using computational tools is a non-trivial task and does not always
      yield ideal results. RESULTS: We propose a new approach SPEL (specificity
      positions by evolutionary likelihood) to detect positions that are likely to be
      functional specificity determinants. SPEL, which does not require subgroup
      definition, takes a multiple sequence alignment of a protein family as the only
      input, and assigns a P-value to every position in the alignment. Positions with
      low P-values are likely to be important for functional specificity. An
      evolutionary tree is reconstructed during the calculation, and P-value estimation
      is based on a random model that involves evolutionary simulations. Evolutionary
      log-likelihood is chosen as a measure of amino acid distribution at a position.
      To illustrate the performance of the method, we carried out a detailed analysis
      of two protein families (LacI/PurR and G protein alpha subunit), and compared our
      method with two existing methods (evolutionary trace and mutual information
      based). All three methods were also compared on a set of protein families with
      known ligand-bound structures. AVAILABILITY: SPEL is freely available for non
      commercial use. Its pre-compiled versions for several platforms and alignments
      used in this work are available at ftp://iole.swmed.edu/pub/SPEL/

PMID- 16278238
TI  - Pathway recognition and augmentation by computational analysis of microarray
      expression data.
AB  - MOTIVATION: We present a system, QPACA (Quantitative Pathway Analysis in Cancer)
      for analysis of biological data in the context of pathways. QPACA supports data
      visualization and both fine- and coarse-grained specifications, but, more
      importantly, addresses the problems of pathway recognition and pathway
      augmentation. RESULTS: Given a set of genes hypothesized to be part of a pathway
      or a coordinated process, QPACA is able to reliably distinguish true pathways
      from non-pathways using microarray expression data. Relying on the observation
      that only some of the experiments within a dataset are relevant to a specific
      biochemical pathway, QPACA automates selection of this subset using an
      optimization procedure. We present data on all human and yeast pathways found in
      the KEGG pathway database. In 117 out of 191 cases (61%), QPACA was able to
      correctly identify these positive cases as bona fide pathways with p-values
      measured using rigorous permutation analysis. Success in recognizing pathways was
      dependent on pathway size, with the largest quartile of pathways yielding 83%
      success. In cross-validation tests of pathway membership prediction, QPACA was
      able to yield enrichments for predicted pathway genes over random genes at rates
      of 2-fold or better the majority of the time, with rates of 10-fold or better 10
      20% of the time. AVAILABILITY: The software is available for academic research
      use free of charge by email request. SUPPLEMENTARY INFORMATION: Data used in the
      paper may be downloaded from http://www.jainlab.org/downloads.html

PMID- 16278239
TI  - Residue-rotamer-reduction algorithm for the protein side-chain conformation
      problem.
AB  - MOTIVATION: The protein side-chain conformation problem is a central problem in
      proteomics with wide applications in protein structure prediction and design.
      Computational complexity results show that the problem is hard to solve. Yet,
      instances from realistic applications are large and demand fast and reliable
      algorithms. RESULTS: We propose a new global optimization algorithm, which for
      the first time integrates residue reduction and rotamer reduction techniques
      previously developed for the protein side-chain conformation problem. We show
      that the proposed approach simplifies dramatically the topology of the
      underlining residue graph. Computations show that our algorithm solves problems
      using only 1-10% of the time required by the mixed-integer linear programming
      approach available in the literature. In addition, on a set of hard side-chain
      conformation problems, our algorithm runs 2-78 times faster than SCWRL 3.0, which
      is widely used for solving these problems. AVAILABILITY: The implementation is
      available as an online server at http://eudoxus.scs.uiuc.edu/r3.html

PMID- 16278240
TI  - PCP: a program for supervised classification of gene expression profiles.
AB  - PCP (Pattern Classification Program) is an open-source machine learning program
      for supervised classification of patterns (vectors of measurements). The
      principal use of PCP in bioinformatics is design and evaluation of classifiers
      for use in clinical diagnostic tests based on measurements of gene expression.
      PCP implements leading pattern classification and gene selection algorithms and
      incorporates cross-validation estimation of classifier performance. Importantly,
      the implementation integrates gene selection and class prediction stages, which
      is vital for computing reliable performance estimates in small-sample scenarios.
      Additionally, the program includes automated and efficient model selection
      (optimization of parameters) for support vector machine (SVM) classifier. The
      distribution includes Linux and Windows/Cygwin binaries. The program can easily
      be ported to other platforms. AVAILABILITY: Free download at
      http://pcp.sourceforge.net

PMID- 16278241
TI  - Systematic intervention of transcription for identifying network response to
      disease and cellular phenotypes.
AB  - MOTIVATION: A major challenge in post-genomic research has been to understand how
      physiological and pathological phenotypes arise from the networks of expressed
      genes. Here, we addressed this issue by developing an algorithm to mimic the
      behavior of regulatory networks in silico and to identify the dynamic response to
      disease and changing cellular conditions. RESULTS: With regulatory pathway and
      gene expression data as input, the algorithm provides quantitative assessments of
      a wide range of responses, including susceptibility to disease, potential
      usefulness of a given drug, or consequences to such external stimuli as
      pharmacological interventions or caloric restriction. The algorithm is
      particularly amenable to the analysis of systems that are difficult to
      recapitulate in vitro, yet they may have important clinical value. The hypotheses
      derived from the algorithm were biologically relevant and were successfully
      validated via independent experiments, as illustrated here in the analysis of the
      leukemia-associated BCR-ABL pathway and the insulin/IGF pathway related to
      longevity. The algorithm correctly identified the leukemia drug target and genes
      important for longevity, and also provided new insights into our understanding of
      these two processes. AVAILABILITY: The software package is available upon request
      to the authors.

PMID- 16278242
TI  - Commentary: varying relation of socioeconomic status with obesity between
      countries at different stages of development.

PMID- 16278243
TI  - Weight change and risk of endometrial cancer.
AB  - BACKGROUND: Obesity is an established risk factor for endometrial cancer. Less
      well understood is the role of weight gain and weight change in determining risk.
      METHODS: We analysed data from a population-based case-control study to evaluate
      the associations of body mass index (BMI), weight gain, and weight cycling with
      risk of endometrial cancer. Cases (n=740) under age 80 with a new diagnosis of
      endometrial cancer were identified from Wisconsin's cancer registry. Controls
      (n=2342) were randomly selected from driver's license lists and Medicare
      beneficiary files. Body size at three time points and other risk factor
      information were ascertained by interview in 1992-95. RESULTS: Endometrial cases
      were more likely than controls to be nulliparous, have early ages at menarche and
      late ages at menopause, be diabetic, smoke cigarettes, and use post-menopausal
      hormones. After adjustment for these factors, increasing BMI was associated with
      increased risk (P-trend<0.001); women in the top quartile of BMI (>29 kg/m2) had
      a 3-fold greater risk of endometrial cancer [95% confidence interval (95% CI) 2.4
      4.2] compared with women in the lowest quartile (<23 kg/-m2). For each 5 kg
      weight gain, the odds ratio (OR) for endometrial cancer risk equalled 1.2 (95% CI
      1.2-1.3). History of weight cycling modestly increased risk after adjustment for
      BMI and other factors (OR=1.3; 95% CI 1.0-1.6). In addition, women who reported
      sustained weight loss had a reduced risk of endometrial cancer (OR=0.7; 95% CI
      0.6-0.9). CONCLUSIONS: These results suggest that weight gain and lack of weight
      stability are associated with risk of endometrial cancer.

PMID- 16278244
TI  - The mass, but not the frequency, of insulin secretory bursts in isolated human
      islets is entrained by oscillatory glucose exposure.
AB  - Insulin is secreted in discrete insulin secretory bursts. Regulation of insulin
      release is accomplished almost exclusively by modulation of insulin pulse mass,
      whereas the insulin pulse interval remains stable at approximately 4 min. It has
      been reported that in vivo insulin pulses can be entrained to a pulse interval of
      approximately 10 min by infused glucose oscillations. If oscillations in glucose
      concentration play an important role in the regulation of pulsatile insulin
      secretion, abnormal or absent glucose oscillations, which have been described in
      type 2 diabetes, might contribute to the defective insulin secretion. Using
      perifused human islets exposed to oscillatory vs. constant glucose, we questioned
      1) whether the interval of insulin pulses released by human islets is entrained
      to infused glucose oscillations and 2) whether the exposure of islets to
      oscillating vs. constant glucose confers an increased signal for insulin
      secretion. We report that oscillatory glucose exposure does not entrain insulin
      pulse frequency, but it amplifies the mass of insulin secretory bursts that
      coincide with glucose oscillations (P < 0.001). Dose-response analyses showed
      that the mode of glucose drive does not influence total insulin secretion (P =
      not significant). The apparent entrainment of pulsatile insulin to infused
      glucose oscillations in nondiabetic humans in vivo might reflect the
      amplification of underlying insulin secretory bursts that are detected as
      entrained pulses at the peripheral sampling site, but without changes in the
      underlying pacemaker activity.

PMID- 16278245
TI  - Metabolic response to carbohydrate ingestion during exercise in males and
      females.
AB  - The present study investigated potential sex-related differences in the metabolic
      response to carbohydrate (CHO) ingestion during exercise. Moderately endurance
      trained men and women (n = 8 for each sex) performed 2 h of cycling at
      approximately 67% Vo(2 max) with water (WAT) or CHO ingestion (1.5 g of
      glucose/min). Substrate oxidation and kinetics were quantified during exercise
      using indirect calorimetry and stable isotope techniques ([(13)C]glucose
      ingestion, [6,6-(2)H(2)]glucose, and [(2)H(5)]glycerol infusion). In both sexes,
      CHO ingestion significantly increased the rates of appearance (R(a)) and
      disappearance (R(d)) of glucose during exercise compared with WAT ingestion
      [males: WAT, approximately 28-29 micromol x kg lean body mass (LBM)(-1) x min(
      1); CHO, approximately 53 micromol x kg LBM(-1) x min(-1); females: WAT,
      approximately 28-29 micromol x kg LBM(-1) x min(-1); CHO, approximately 61
      micromol x kg LBM(-1) x min(-1); main effect of trial, P < 0.05]. The
      contribution of plasma glucose oxidation to the energy yield was significantly
      increased with CHO ingestion in both sexes (from approximately 10% to
      approximately 20% of energy expenditure; main effect of trial, P < 0.05). Liver
      derived glucose oxidation was reduced, although the rate of muscle glycogen
      oxidation was unaffected with CHO ingestion (males: WAT, 108 +/- 12 micromol x kg
      LBM(-1) x min(-1); CHO, 108 +/- 11 micromol x kg LBM(-1) x min(-1); females: WAT,
      89 +/- 10 micromol x kg LBM(-1) x min(-1); CHO, 93 +/- 11 micromol x kg LBM(-1) x
      min(-1)). CHO ingestion reduced fat oxidation and lipolytic rate (R(a) glycerol)
      to a similar extent in both sexes. Finally, ingested CHO was oxidized at similar
      rates in men and women during exercise (peak rates of 0.70 +/- 0.08 and 0.65 +/-
      0.06 g/min, respectively). The present investigation suggests that the metabolic
      response to CHO ingestion during exercise is largely similar in men and women.

PMID- 16278246
TI  - Evidence against regulation of AMP-activated protein kinase and LKB1/STRAD/MO25
      activity by creatine phosphate.
AB  - Muscle contraction results in phosphorylation and activation of the AMP-activated
      protein kinase (AMPK) by an AMPK kinase (AMPKK). LKB1/STRAD/MO25 (LKB1) is the
      major AMPKK in skeletal muscle; however, the activity of LKB1 is not increased by
      muscle contraction. This finding suggests that phosphorylation of AMPK by LKB1 is
      regulated by allosteric mechanisms. Creatine phosphate is depleted during
      skeletal muscle contraction to replenish ATP. Thus the concentration of creatine
      phosphate is an indicator of cellular energy status. A previous report found that
      creatine phosphate inhibits AMPK activity. The purpose of this study was to
      determine whether creatine phosphate would inhibit 1) phosphorylation of AMPK by
      LKB1 and 2) AMPK activity after phosphorylation by LKB1. We found that creatine
      phosphate did not inhibit phosphorylation of either recombinant or purified rat
      liver AMPK by LKB1. We also found that creatine phosphate did not inhibit 1)
      active recombinant alpha1beta1gamma1 or alpha2beta2gamma2 AMPK, 2) AMPK
      immunoprecipitated from rat liver extracts by either the alpha1 or alpha2
      subunit, or 3) AMPK chromatographically purified from rat liver. Inhibition of
      skeletal muscle AMPK by creatine phosphate was greatly reduced or eliminated with
      increased AMPK purity. In conclusion, these results suggest that creatine
      phosphate is not a direct regulator of LKB1 or AMPK activity. Creatine phosphate
      may indirectly modulate AMPK activity by replenishing ATP at the onset of muscle
      contraction.

PMID- 16278247
TI  - Overexpression of the insulin receptor inhibitor PC-1/ENPP1 induces insulin
      resistance and hyperglycemia.
AB  - The ectoenzyme PC-1 is an insulin receptor inhibitor that is elevated in cells
      and tissues of humans with type 2 diabetes (T2D). We have recently shown that
      acute PC-1 overexpression in liver causes insulin resistance and glucose
      intolerance in mice (3), but the chronic effects of PC-1 overexpression on these
      functions are unknown. Herein we produced transgenic mice overexpressing the
      potent q allele of human PC-1 in muscle and liver. Compared with controls, these
      mice had 2- to 3-fold elevations of PC-1 content in liver and 5- to 10-fold
      elevations in muscle. In the fed state, the PC-1 animals had 100 mg/dl higher
      glucose levels and sixfold higher insulin levels compared with controls. During
      glucose tolerance tests, these PC-1 animals had peak glucose levels that were
      >150 mg/dl higher than controls. In vivo uptake of 2-deoxy-d-glucose in muscle
      during insulin infusion was decreased in the PC-1 animals. These in vivo data
      support the concept, therefore, that PC-1 plays a role in insulin resistance and
      hyperglycemia and suggest that animals with overexpression of human PC-1 in
      insulin-sensitive tissues may be important models to investigate insulin
      resistance.

PMID- 16278248
TI  - Compartmental distribution of amino acids during hemodialysis-induced
      hypoaminoacidemia.
AB  - The intracellular concentrations of essential amino acids (EAA) in muscle are
      maintained relatively constant under a variety of conditions. However, the effect
      of a decrease in blood amino acid concentrations on intracellular concentrations
      is not clear. Similarly, the relation between intracellular and interstitial
      concentrations has not been determined in this circumstance. Thus the aim of this
      study was to determine the effect of hypoaminoacidemia on intracellular,
      interstitial, and plasma concentrations of EAA and the mechanisms responsible for
      the respective changes. Twelve normal pigs were investigated before and during
      120 min of hemodialysis by use of stable-isotope tracer methodology,
      microdialysis technique, and muscle biopsies. During hemodialysis, there was a
      decrease in the interstitial fluid concentrations of phenylalanine, leucine,
      alanine, and lysine that corresponded to their decrease in plasma concentration.
      Nonetheless, the intracellular concentrations of these amino acids were
      maintained at the basal levels throughout the entire period due principally to a
      reduction in the rate of incorporation of amino acids into protein that was
      approximately equivalent to the decrease in uptake from the plasma. In
      conclusion, intracellular concentrations of amino acids are regulated to maintain
      relatively constant values, even when plasma and interstitial concentrations fall
      as a consequence of hemodialysis.

PMID- 16278249
TI  - Measurements of insulin responses as predictive markers of pancreatic beta-cell
      mass in normal and beta-cell-reduced lean and obese Gottingen minipigs in vivo.
AB  - At present, the best available estimators of beta-cell mass in humans are those
      based on measurement of insulin levels or appearance rates in the circulation. In
      several animal models, these estimators have been validated against beta-cell
      mass in lean animals. However, as many diabetic humans are obese, a correlation
      between in vivo tests and beta-cell mass must be evaluated over a range of body
      weights to include different levels of insulin sensitivity. For this purpose,
      obese (n = 10) and lean (n = 25) Gottingen minipigs were studied. Beta-cell mass
      had been reduced (n = 16 lean, n = 5 obese) with a combination of nicotinamide
      (67 mg/kg) and streptozotocin (125 mg/kg), acute insulin response (AIR) to
      intravenous glucose and/or arginine was tested, pulsatile insulin secretion was
      evaluated by deconvolution (n = 30), and beta-cell mass was determined
      histologically. AIR to 0.3 (r(2) = 0.4502, P < 0.0001) or 0.6 g/kg glucose (r(2)
      = 0.6806, P < 0.0001), 67 mg/kg arginine (r(2) = 0.5730, P < 0.001), and maximum
      insulin concentration (r(2) = 0.7726, P < 0.0001) were all correlated to beta
      cell mass when evaluated across study groups, and regression lines were not
      different between lean and obese groups except for AIR to 0.3 g/kg glucose.
      Baseline pulse mass was not significantly correlated to beta-cell mass across the
      study groups (r(2) = 0.1036, NS), whereas entrained pulse mass did show a
      correlation across groups (r(2) = 0.4049, P < 0.001). This study supports the use
      of in vivo tests of insulin responses to evaluate beta-cell mass over a range of
      body weights in the minipig. Extensive stimulation of insulin secretion by a
      combination of glucose and arginine seems to give the best correlation to beta
      cell mass.

PMID- 16278250
TI  - PPARdelta activator GW-501516 has no acute effect on glucose transport in
      skeletal muscle.
AB  - It has been reported that treatment of cultured human skeletal muscle myotubes
      with the peroxisome proliferator-activated receptor-delta (PPARdelta) activator
      GW-501516 directly stimulates glucose transport and enhances insulin action.
      Cultured myotubes are minimally responsive to insulin stimulation of glucose
      transport and are not a good model for studying skeletal muscle glucose
      transport. The purpose of this study was to evaluate the effect of GW-501516 on
      glucose transport to determine whether the findings on cultured myotubes have
      relevance to skeletal muscle. Rat epitrochlearis and soleus muscles were treated
      for 6 h with 10, 100, or 500 nM GW-501516, followed by measurement of 2
      deoxyglucose uptake. GW-501516 had no effect on glucose uptake. There was no
      effect on insulin sensitivity or responsiveness. Also, in contrast to findings on
      myotubes, treatment of muscles with GW-501516 did not result in increased
      phosphorylation or increased expression of AMP-activated protein kinase (AMPK) or
      p38 mitogen-activated protein kinase (MAPK). Treatment of epitrochlearis muscles
      with GW-501516 for 24 h induced a threefold increase in uncoupling protein-3
      mRNA, providing evidence that the GW-501516 compound that we used gets into and
      is active in skeletal muscle. In conclusion, our results show that, in contrast
      to myotubes in culture, skeletal muscle does not respond to GW-501516 with 1) an
      increase in AMPK or p38 MAPK phosphorylation or expression or 2) direct
      stimulation of glucose transport or enhanced insulin action.

PMID- 16278251
TI  - Thermogenic responsiveness to nonspecific beta-adrenergic stimulation is not
      related to genetic variation in codon 16 of the beta2-adrenergic receptor.
AB  - Stimulation of beta-adrenergic receptors (beta-AR) by the sympathetic nervous
      system (SNS) modulates energy expenditure (EE), but substantial interindividual
      variability is observed. We determined whether the thermogenic response to beta
      AR stimulation is related to genetic variation in codon 16 of the beta(2)-AR, a
      biologically important beta-AR polymorphism, and whether differences in SNS
      activity (i.e., the stimulus for agonist-promoted downregulation) are involved.
      The increase in EE (DeltaEE, indirect calorimetry, ventilated hood) above resting
      EE in response to nonspecific beta-AR stimulation [iv isoproterenol: 6, 12, and
      24 ng/kg fat-free mass (FFM)/min] was measured in 46 healthy adult humans
      [Arg16Arg: 9 male, 7 female, 48 +/- 5 yr; Arg16Gly: 11 male, 4 female, 53 +/- 5
      yr; Gly16Gly: 3 male, 12 female, 48 +/- 5 yr (means +/- SE)]. Neither FFM
      adjusted baseline resting EE (P = 0.83) nor the dose of isoproterenol required to
      increase EE 10% above resting (P = 0.87) differed among the three groups
      (Arg16Arg: 5,409 +/- 209 kJ/day, 11.2 +/- 2.1 ng x kg FFM(-1) x min(-1);
      Arg16Gly: 5,367 +/- 272 kJ/day, 11.1 +/- 2.1 ng x kg FFM(-1) x min(-1); Gly16Gly:
      5,305 +/- 159 kJ/day, 10.5 +/- 1.4 ng x kg FFM(-1) x min(-1)). Consistent with
      this, muscle sympathetic nerve activity and plasma norepinephrine concentrations
      were not different among the groups. Group differences in sex composition did not
      influence the results. Our findings indicate that the thermogenic response to
      nonspecific beta-AR stimulation, an important mechanistic component of overall
      beta-AR modulation of EE, is not related to this beta(2)-AR polymorphism in
      healthy humans. This may be explained in part by a lack of association between
      this gene variant and tonic SNS activity.

PMID- 16278252
TI  - Regulation of cardiac and skeletal muscle protein synthesis by individual
      branched-chain amino acids in neonatal pigs.
AB  - Skeletal muscle grows at a very rapid rate in the neonatal pig, due in part to an
      enhanced sensitivity of protein synthesis to the postprandial rise in amino
      acids. An increase in leucine alone stimulates protein synthesis in skeletal
      muscle of the neonatal pig; however, the effect of isoleucine and valine has not
      been investigated in this experimental model. The left ventricular wall of the
      heart grows faster than the right ventricular wall during the first 10 days of
      postnatal life in the pig. Therefore, the effects of individual BCAA on protein
      synthesis in individual skeletal muscles and in the left and right ventricular
      walls were examined. Fasted pigs were infused with 0 or 400 micromol x kg(-1) x
      h(-1) leucine, isoleucine, or valine to raise individual BCAA to fed levels.
      Fractional rates of protein synthesis and indexes of translation initiation were
      measured after 60 min. Infusion of leucine increased (P < 0.05) phosphorylation
      of eukaryotic initiation factor (eIF)4E-binding protein-1 and increased (P <
      0.05) the amount and phosphorylation of eIF4G associated with eIF4E in
      longissimus dorsi and masseter muscles and in both ventricular walls. Leucine
      increased (P < 0.05) the phosphorylation of ribosomal protein (rp)S6 kinase and
      rpS6 in longissimus dorsi and masseter but not in either ventricular wall.
      Leucine stimulated (P < 0.05) protein synthesis in longissimus dorsi, masseter,
      and the left ventricular wall. Isoleucine and valine did not increase translation
      initiation factor activation or protein synthesis rates in skeletal or cardiac
      muscles. The results suggest that the postprandial rise in leucine, but not
      isoleucine or valine, acts as a nutrient signal to stimulate protein synthesis in
      cardiac and skeletal muscles of neonates by increasing eIF4E availability for
      eIF4F complex assembly.

PMID- 16278253
TI  - Renal protection in immunoglobulin-A nephropathy.

PMID- 16278254
TI  - Possible new perspectives for our understanding of nephrotic syndrome recurrence.

PMID- 16278255
TI  - Dual blockade of renin-angiotensin system in primary focal segmental
      glomerulosclerosis.

PMID- 16278256
TI  - Medications associated with weight gain.
AB  - OBJECTIVE: To review available literature regarding weight gain associated with
      commonly prescribed drugs and adjunctive therapy used to limit weight gain. DATA
      SOURCES: Information was retrieved from a MEDLINE English-literature search
      between 1995 and July 2005, with a major subject heading of weight gain/drug
      effects excluding complementary alternative medicines. Other limits applied
      included human subjects and individuals >19 years of age. Additionally,
      references from retrieved articles were reviewed to identify other literature
      sources. STUDY SELECTION AND DATA EXTRACTION: Changes in weight are generally
      reported as a primary or secondary outcome of many studies. Where possible,
      prospective, randomized, controlled trials were preferred; however, many studies
      were retrospective or open label. Meta-analyses and recent reviews, especially
      those providing a detailed description of the proposed mechanism involved in
      weight gain beyond the scope of this article, were included. Limited information
      was available from case reports. Studies were categorized by therapeutic area
      including psychiatry, neurology, diabetes, and other miscellaneous drug therapy.
      Medications used to intentionally stimulate appetite for weight gain, such as
      megesterol acetate, were not included. DATA SYNTHESIS: Weight gain with
      medication is usually associated with individual agents within a class. The
      tendency to cause weight gain is often related to differential specificity and
      sensitivity of binding to receptors involved with appetite regulation.
      CONCLUSIONS: Clinically significant weight gain is associated with some commonly
      prescribed medicines. There is wide interindividual variation in response and
      variation of the degree of weight gain within drug classes. Where possible,
      alternative therapy should be selected, especially for individuals predisposed to
      overweight and obesity.

PMID- 16278257
TI  - Mometasone furoate improves congestion in patients with moderate-to-severe
      seasonal allergic rhinitis.
AB  - BACKGROUND: A recent survey estimated that 85% of patients with allergic rhinitis
      experience nasal congestion. This symptom considerably impacts quality of life.
      OBJECTIVE: To evaluate the effectiveness of mometasone furoate nasal spray (MFNS)
      in subjects with seasonal allergic rhinitis (SAR) experiencing moderate-to-severe
      nasal congestion. METHODS: Data were obtained from 4 randomized, double-blind,
      placebo-controlled studies of MFNS 200 microg once daily in patients with SAR.
      Subject-evaluated nasal congestion score data (score range 0-3) from subjects
      receiving MFNS or placebo were analyzed as a pool and grouped according to
      baseline score (all pts. with scores >2.5, >2.75, or 3.0). The 2-week average
      change in score from baseline was analyzed. RESULTS: Significant improvements in
      mean nasal congestion score were seen with MFNS (n = 490) versus placebo (n =
      492; p < 0.001). Overall, there was a 27% improvement in this score in patients
      receiving MFNS versus 13% with placebo. MFNS produced significant reductions in
      the nasal congestion score compared with placebo, even in patients with the most
      severe baseline congestion (0.98 vs 0.52; p < 0.001). Improvements in scores from
      baseline of 32%, 33%, and 34% were seen with MFNS versus 22%, 21%, and 18% with
      placebo (for baseline scores of >2.5, >2.75, or 3.0, respectively), confirming
      the effectiveness of MFNS regardless of congestion severity. This represents an
      improvement approximating a decrease from severe to moderate congestion or from
      moderate-to-severe to mild-to-moderate congestion. MFNS was well tolerated.
      CONCLUSIONS: MFNS 200 microg once daily produces statistically significant
      improvements in nasal congestion score compared with placebo, alleviating severe
      congestion in patients with moderate-to-severe SAR.

PMID- 16278258
TI  - Treatment for allergic rhinitis and chronic idiopathic urticaria: focus on oral
      antihistamines.
AB  - OBJECTIVE: To review the efficacy and safety of first- and newer-generation
      antihistamines for the management of allergic rhinitis and chronic idiopathic
      urticaria (CIU), with a focus on management in the pharmacy. DATA SOURCES: A
      literature review was performed using MEDLINE (1966-October 2005), with no time
      or language restrictions. Key words or phrases used were histamine,
      antihistamine(s), first- and second-generation, allergic rhinitis, chronic
      idiopathic urticaria, quality of life, impairment, sedation, cost-effectiveness,
      astemizole, cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine,
      hydroxyzine, ketotifen, and mizolastine. Additional references were found in the
      bibliographies of the articles cited. STUDY SELECTION AND DATA EXTRACTION:
      Clinical trials and other experimental studies of the use of antihistamines for
      the management of allergic rhinitis and CIU were selected. Review papers and
      guidelines were also included. DATA SYNTHESIS: First-generation antihistamines
      are effective at ameliorating the symptoms of allergic rhinitis and CIU; however,
      they are associated with adverse effects due to a lack of selectivity for the
      histamine H(1)-receptor and an ability to bind to cerebral H(1)-receptors. Newer
      generation agents, in general, possess high H(1)-receptor selectivity and a low
      tendency to cross the blood-brain barrier, while maintaining efficacy. In
      general, safety at elevated doses has been demonstrated for the newer
      antihistamines, although higher rates of sedation and impairment have been
      reported with increasing doses for some agents. CONCLUSIONS: Pharmacists can play
      an important role in the management of allergic rhinitis and CIU by considering
      the relative advantages of newer-generation agents when reviewing treatment
      options.

PMID- 16278259
TI  - Elevated peptide YY levels in adolescent girls with anorexia nervosa.
AB  - BACKGROUND: Peptide YY (PYY) is an intestinally derived anorexigen that acts via
      the Y2 receptor, and Y2 receptor deletion in rodents increases bone formation.
      Anorexia nervosa (AN) is associated with a deliberate reduction in food intake
      and low bone density, but endocrine modulators of food intake in AN are not
      known. In addition, known regulators of bone turnover, such as GH, cortisol, and
      estrogen, explain only a fraction of the variability in bone turnover marker
      levels. HYPOTHESES: We hypothesized that PYY may be elevated in AN compared with
      controls and may contribute to decreased food intake and bone formation. METHODS:
      Fasting PYY was examined in 23 AN girls and 21 healthy adolescents 12-18 yr old.
      We also examined GH, cortisol, ghrelin, and leptin (overnight frequent sampling)
      and fasting IGF-I, estradiol, total T3, and bone markers. Macronutrient intake
      and resting energy expenditure (REE) were measured. RESULTS: AN girls had higher
      PYY levels compared with controls (17.8 +/- 10.2 vs. 4.8 +/- 4.3 pg/ml; P <
      0.0001). Predictors of log PYY were nutritional markers, including body mass
      index (r = -0.62; P < 0.0001), fat mass (r = -0.55; P = 0.0003), and REE (r = 
      0.51; P = 0.0006), and hormones, including GH (r = 0.38; P = 0.004) and T3 (r = 
      0.59; P = 0.0001). Body mass index, fat mass, REE, GH, and T3 explained 68% of
      the variability of log PYY. Log PYY predicted percentage of calories from fat (r
      = -0.56; P = 0.0002) and independently predicted osteocalcin (r = -0.45; P =
      0.003), bone-specific alkaline phosphatase (r = -0.46; P = 0.003), N
      telopeptide/creatinine (r = -0.55; P = 0.0003), and deoxypyridinoline/creatinine
      (r = -0.52; P = 0.001) on regression modeling. CONCLUSION: Elevated PYY may
      contribute to reduced intake and decreased bone turnover in AN.

PMID- 16278260
TI  - Levonorgestrel implants enhanced the suppression of spermatogenesis by
      testosterone implants: comparison between Chinese and non-Chinese men.
AB  - CONTEXT: Previous male contraceptive studies showed that progestins enhance
      spermatogenesis suppression by androgens in men. OBJECTIVE: We compared the
      efficacy of spermatogenesis suppression by the combination of levonorgestrel
      (LNG) with testosterone (T) implants to that by T implants alone in two different
      ethnic groups. DESIGN: This was a randomized trial performed in two centers with
      two treatment groups. SETTINGS: The study was performed at the Academic Medical
      Center in the United States and the Research Institute in China. PARTICIPANTS:
      Forty non-Chinese and 40 Chinese healthy male volunteers were studied.
      INTERVENTIONS: Subjects were randomized to receive four LNG implants together
      with four T implants (inserted on d 1 and wk 15-18) vs. T implants alone for 30
      wk. MAIN OUTCOME MEASURES: The primary end point compared the efficiency of
      suppression to severe oligozoospermia (1 x 10(6)/ml) by LNG plus T implants vs.
      that by T implants alone. The secondary end point examined differences in
      spermatogenesis suppression between Chinese and non-Chinese subjects. RESULTS:
      LNG plus T implants caused more suppression of spermatogenesis to severe
      oligozoospermia during the treatment period than T implants alone at both sites
      (P < 0.02). In Chinese men, severe oligozoospermia was achieved in more than 90%
      of the men in both treatment groups. Suppression to severe oligozoospermia was
      less in the non-Chinese men (59%) after T alone (P < 0.020); this difference
      disappeared with combined treatment (89%). T implant extrusion occurred in six
      men. Acne and increased hemoglobin were the most common adverse events.
      CONCLUSION: T implants resulted in more pronounced spermatogenesis suppression in
      Chinese men. Addition of LNG implants to T implants enhanced the suppression of
      spermatogenesis in the treatment period in both Chinese and non-Chinese men.

PMID- 16278261
TI  - Presence and absence of follicle-stimulating hormone receptor mutations provide
      some insights into spontaneous ovarian hyperstimulation syndrome physiopathology.
AB  - CONTEXT: Ovarian hyperstimulation syndrome (OHSS) is a potentially life
      threatening complication of ovarian stimulation treatments. Moreover, four
      mutations of the FSH receptor (FSHr) were recently described in patients
      presenting with spontaneous OHSS (sOHSS) of the first trimester of pregnancy with
      normal levels of human chorionic gonadotropin (hCG). OBJECTIVE: The objective of
      this study was to look for novel FSHr mutations in patients with sOHSS associated
      with different levels of hCG and TSH to 1) find new residues important for FSHr
      activation and specificity, and 2) better delineate the pathophysiology of the
      different presentations of sOHSS. DESIGN, INTERVENTION, AND PATIENTS: After blood
      sampling, we sequenced the FSHr from genomic leukocytes DNA from eight patients
      with sOHSS of the first or second trimester of pregnancy with normal or high hCG
      levels or with high TSH levels associated with severe hypothyroidism. SETTING:
      This study was performed at a university laboratory. MAIN OUTCOME MEASURE: The
      main outcome measure was FSHr sequencing and in vitro evaluation of the variation
      of cAMP production of FSHr mutants. RESULTS: A new mutation was found in the
      patient with sOHSS of the first trimester of pregnancy with a normal hCG level:
      I5.54(545)T, in transmembrane helix V of the FSHr. When tested functionally, this
      mutant displayed promiscuous activation by both hCG and TSH together with
      detectable constitutive activity. In contrast, no mutations were found in the
      FSHr from patients with high hCG or TSH levels, indicating that for those seven
      patients, sOHSS results from the natural promiscuous stimulation of a wild-type
      FSHr by very high concentrations of hCG or TSH. CONCLUSIONS: sOHSS can occur by
      at least three different pathophysiological mechanisms.

PMID- 16278263
TI  - "Hook effect" in calcitonin immunoradiometric assay in patients with metastatic
      medullary thyroid carcinoma: case report and review of the literature.
AB  - CONTEXT: Calcitonin is a well-established tumor marker for medullary thyroid
      carcinoma (MTC). Because surgery is the only effective treatment for patients
      with MTC, the postoperative level of serum calcitonin will dictate whether
      residual disease was left behind and whether reintervention is necessary.
      RESULTS: We describe here the case of a 41-yr-old man with metastatic MTC.
      Despite extensive disease in the neck as well as metastatic lesions in the liver,
      his serum calcitonin, measured with a commercial one-step immunoradiometric
      assay, was only minimally elevated (244 ng/liter). After serial dilutions, a
      nonlinear relationship became evident, suggesting the presence of a "hook
      effect." Treatment of the serum with heterophilic blocking reagent revealed no
      change. Calcitonin was then measured with a different immunoradiometric assay and
      revealed a much higher level. Similar discrepancies were found in different
      samples from various patients when analyzed with different calcitonin
      immunoassays. CONCLUSION: To our knowledge, this is the first reported case of a
      phenomenon such as the hook effect in a calcitonin immunoradiometric assay in
      patients with MTC. Being aware of this phenomenon is important, because a low
      calcitonin result could give false reassurance to both the patient and the
      clinician and could dramatically change the prognosis of the patient.

PMID- 16278262
TI  - Effect of vitamin D replacement on musculoskeletal parameters in school children:
      a randomized controlled trial.
AB  - BACKGROUND: Despite the high prevalence of hypovitaminosis D in children and
      adolescents worldwide, the impact of vitamin D deficiency on skeletal health is
      unclear. METHODS: One hundred seventy-nine girls, ages 10-17 yr, were randomly
      assigned to receive weekly oral vitamin D doses of 1,400 IU (equivalent to 200
      IU/d) or 14,000 IU (equivalent to 2,000 IU/d) in a double-blind, placebo
      controlled, 1-yr protocol. Areal bone mineral density (BMD) and bone mineral
      content (BMC) at the lumbar spine, hip, forearm, total body, and body composition
      were measured at baseline and 1 yr. Serum calcium, phosphorus, alkaline
      phosphatase, and vitamin D metabolites were measured during the study. RESULTS:
      In the overall group of girls, lean mass increased significantly in both
      treatment groups (P < or = 0.05); bone area and total hip BMC increased in the
      high-dose group (P < 0.02). In premenarcheal girls, lean mass increased
      significantly in both treatment groups, and there were consistent trends for
      increments in BMD and/or BMC at several skeletal sites, reaching significance at
      lumbar spine BMD in the low-dose group and at the trochanter BMC in both
      treatment groups. There was no significant change in lean mass, BMD, or BMC in
      postmenarcheal girls. CONCLUSIONS: Vitamin D replacement had a positive impact on
      musculoskeletal parameters in girls, especially during the premenarcheal period.

PMID- 16278264
TI  - Serial analysis of gene expression in adrenocortical hyperplasia caused by a
      germline PRKAR1A mutation.
AB  - CONTEXT: Adrenocortical tumors have been studied at the molecular genetic and
      cytogenetic levels, but the gene expression profiles of normal and tumor adrenal
      tissue have not been extensively investigated. OBJECTIVE: The objective of this
      study was to obtain information about transcriptome differences in hyperplastic
      adrenal cells. DESIGN AND PATIENTS: We performed serial analysis of gene
      expression (SAGE) on control adrenal tissue and primary pigmented nodular
      adrenocortical disease (PPNAD) tissue from two adolescent female patients. MAIN
      OUTCOME MEASURE: The main outcome measure was to provide quantitative datasets of
      the vast majority of the transcripts implicated in normal and pathogenic adrenal
      functioning. RESULTS: The libraries of 28,705 and 31,278 tags represented 14,846
      and 16,698 unique mRNAs from the control and PPNAD tissue, respectively. A total
      of 842 tags from the two libraries did not match any known sequences. We found
      127 tags, including 70 no-match tags, to be expressed almost exclusively in
      control and/or PPNAD adrenals and to be absent or very rare in other human
      tissues. Examples of well-characterized genes expressed at significantly higher
      levels in PPNAD included steroidogenic acute regulator, chromogranin A, and those
      coding for the steroidogenic enzymes P450 cytochromes CYP17A1 and CYP21A2.
      Pathway analysis revealed Wnt signaling as the most up-regulated in PPNAD. These
      data were confirmed for selected genes by quantitative RT-PCR and/or
      immunohistochemistry. CONCLUSIONS: This study was the first of its kind for
      adrenal tissue and provides important information about the adrenal transcriptome
      and aberrant signaling in an inherited form of adrenocortical hyperplasia.

PMID- 16278265
TI  - A homozygous mutation in the lamin A/C gene associated with a novel syndrome of
      arthropathy, tendinous calcinosis, and progeroid features.
AB  - CONTEXT: Mutations in the lamin A/C (LMNA) gene have been reported in a wide
      variety of disorders, including lipodystrophies, cardiomyopathy, muscular
      dystrophies, neuropathy, mandibuloacral dysplasia, restrictive dermopathy, and
      progeria. OBJECTIVE: The objective of this study was to carry out mutational
      analysis of LMNA in a patient with a novel syndrome of arthropathy, tendinous
      calcinosis, and progeroid features. DESIGN: The study design was a descriptive
      case report. SETTING: The study was performed at a referral center. PATIENT: A 44
      yr-old male of European descent with an autosomal recessive arthropathy syndrome
      affecting predominantly the distal femora and proximal tibia in the knee with
      tendinous calcifications was studied. He also had progeroid features, such as
      pinched nose and micrognathia, cataract, alopecia, generalized lipodystrophy, and
      sclerodermatous skin. MAIN OUTCOME MEASURES: The main outcome measures were
      mutational analysis of lamin A/C (LMNA) and its processing enzyme, zinc
      metalloproteinase (ZMPSTE24), as candidate genes. RESULTS: We found a homozygous
      nucleotide substitution, 1718C>T, in exon 11 of the LMNA gene, resulting in
      substitution of a well-conserved residue serine at position 573 with leucine
      (S573L). This missense mutation only affects lamin A, not lamin C, because the
      alternative splicing site is located in exon 10. Immunofluorescence staining of
      the nuclei from his skin fibroblasts showed occasional misshapen morphology.
      CONCLUSIONS: The S573L homozygous LMNA mutation is associated with a novel
      phenotype of arthropathy, tendinous calcifications, and progeroid features
      distinct from the acroosteolysis previously reported in patients with
      mandibuloacral dysplasia caused by LMNA or ZMPSTE24 mutations. Thus, arthropathy
      with tendinous calcifications can be added to the growing list of disorders
      associated with LMNA mutations.

PMID- 16278266
TI  - Long-term impaired quality of life in Cushing's syndrome despite initial
      improvement after surgical remission.
AB  - CONTEXT: Cushing's syndrome (CS) is associated with symptoms that may impair
      health-related quality of life (HRQL). METHODS: We used the short-form 36 survey
      to evaluate HRQL in 23 patients with Cushing's disease before and after
      transsphenoidal surgery (age, 42.7 +/- 12.0 yr; 19 women and four men) and in a
      cross-section of 343 CS patients (age, 48.2 +/- 14.1 yr; 265 women and 78 men) in
      remission for up to 25.8 yr after surgery (adrenal, 5%; ectopic, 6%). The z
      scores were calculated for short-form 36 domains, and physical (PCS) and mental
      (MCS) summary scores were compared with those of age- and sex-matched controls (n
      = 6742). RESULTS: Active Cushing's disease was associated with low PCS and MCS
      scores (P < 0.05). Despite residual postoperative impairment, primarily of
      physical domains, all HRQL parameters improved after treatment with
      transsphenoidal surgery (3.2 +/- 1.5 yr; P < 0.05). In the cross-section in
      remission at follow-up, there was a small, but significant (P < 0.05), impairment
      of both PCS and MCS. A longitudinal postoperative analysis confirmed stable, but
      impaired, HRQL over time. Logistic regression demonstrated that previous
      pituitary radiation and current glucocorticoid use had little effect on HRQL
      outcomes. CONCLUSION: CS is associated with impaired HRQL, which partially
      resolves after treatment. At longer-term follow-up, however, there is residual
      impairment of HRQL. Determination of modifiable factors that contribute to
      impaired HRQL may help reduce the physical and psychosocial burden of this
      disease.

PMID- 16278267
TI  - The 103I variant of the melanocortin 4 receptor is associated with low serum
      triglyceride levels.
AB  - CONTEXT: The melanocortin 4 receptor (MC4R) is an essential regulator of energy
      intake and body weight. Recently, the V103I polymorphism of MC4R has been shown
      to be negatively associated with body mass index. This suggests that serum lipids
      and blood pressure in individuals carrying the 103I allele might be influenced as
      well. OBJECTIVE: The objective of this study was to determine whether the most
      common polymorphism of the MC4R, V103I, affects serum lipid levels and/or blood
      pressure. DESIGN, SETTING, AND PARTICIPANTS: The study participants were 1173
      consecutive patients undergoing cardiac catheterization; they were genotyped for
      the rs2229616 G-->A substitution at codon 103 (V103I polymorphism) of the MC4R
      gene. Patients had strictly fasted for at least 12 h before blood samples were
      drawn. The average age of the patients was 60.9 yr; 72% were males. MAIN OUTCOME
      MEASURES: The main outcome measures were body mass index, serum lipids, aortic
      and systolic blood pressure, and MC4R polymorphism V103I. RESULTS: Heterozygous
      carriers of the 103I allele had significantly lower triglyceride levels than
      individuals homozygous for the wild-type allele (127 vs. 168 mg/dl mean total
      triglyceride; P = 0.001 or 0.009 after Bonferroni adjustment for seven tests). No
      homozygous carriers of the 103I allele were present in the study population.
      CONCLUSIONS: Our study suggests an influence of MC4R activity on triglyceride
      levels in cardiovascular patients.

PMID- 16278268
TI  - A densitometric and morphometric analysis of the skeleton in adults with varying
      degrees of growth hormone deficiency.
AB  - CONTEXT: Low bone mass is a characteristic feature of the adult GH deficiency
      (GHD) syndrome, but recent dual-energy x-ray absorptiometry (DXA) studies in
      patients with GH-receptor and GHRH-receptor gene mutations suggest that the
      situation is more complex. OBJECTIVE: The objective was to define bone areal and
      volumetric densities and morphometry in hypopituitary adults. DESIGN: The study
      was a cross-sectional case-controlled study performed between 1999 and 2001.
      SETTING: The study was undertaken at an endocrine tertiary referral center.
      PATIENTS: Thirty patients with GHD, 24 with GH insufficiency (GHI) [peak GH, 3-7
      microg/liter (9-21 mU/liter)], and 30 age- and sex-matched controls were included
      for study. MAIN OUTCOME MEASURES: DXA and peripheral quantitative computed
      tomography (pQCT) derived bone density and morphometry were measured. RESULTS: No
      densitometric or morphometric abnormalities were detected in GHD patients who
      acquired their deficiency during adult life. GHD adults of childhood-onset (CO
      GHD) showed decreased bone mineral density at the lumbar spine and hip on DXA.
      pQCT of the radius showed that CO-GHD patients have normal trabecular bone
      mineral density and only a 2% decrease in cortical density. Radial bone area was
      reduced 14.5%, cortical thickness 20%, and cortical cross-sectional area 23%,
      culminating in a reduction in cortical bone of 25%. The "apparent" low DXA bone
      density in CO-GHD adults therefore relates primarily to reduced cortical
      thickness and smaller bone area. DXA and pQCT data derived from adults with GHI
      revealed no evidence of densitometric or morphometric abnormalities. CONCLUSIONS:
      1) Adult-onset GHD patients have normal bone density and size. 2) CO-GHD adults
      have marginally reduced cortical density but significantly reduced cortical bone
      as a result of reduced cortical thickness and bone size. 3) GHI has no measurable
      impact on the skeleton.

PMID- 16278270
TI  - A genome-wide screen in 1119 relative pairs with autoimmune thyroid disease.
AB  - CONTEXT: Autoimmune thyroid diseases (AITD), comprising Graves' disease and
      autoimmune hypothyroidism, are characterized by loss of immunological self
      tolerance to thyroid antigens. These are complex diseases arising from a
      combination of genetic and environmental factors. An understanding of the genetic
      susceptibility factors for AITD could help to target treatments more effectively
      and identify people at risk for these conditions. OBJECTIVE: The objective of
      this study was to identify regions of genetic linkage to AITD that could
      potentially harbor genetic susceptibility factors for these conditions. DESIGN:
      The study design was a genome-wide screen performed on affected relative pairs
      with AITD. SETTING: Patients were recruited through hospital endocrinology
      clinics. PARTICIPANTS: Some 1119 Caucasian relative pairs affected with AITD
      (Graves' disease or autoimmune hypothyroidism) were recruited into the study.
      INTERVENTION: Blood samples were obtained from each participant for DNA analysis,
      and clinical questionnaires were completed. MAIN OUTCOME MEASURE: The study aimed
      to identify regions of genetic linkage to AITD. RESULTS: Three regions of
      suggestive linkage were obtained on chromosomes 18p11 (maximum LOD score, 2.5),
      2q36 (maximum LOD score, 2.2), and 11p15 (maximum LOD score, 2.0). No linkage to
      human leukocyte antigen was found. CONCLUSIONS: The absence of significant
      evidence of linkage at any one locus in such a large dataset argues that genetic
      susceptibility to AITD reflects a number of loci, each with a modest effect.
      Linkage analysis may be limited in defining such loci, and large-scale
      association studies may prove to be more useful in identifying genetic
      susceptibility factors for AITD.

PMID- 16278269
TI  - Long-term corticosteroid replacement and bone mineral density in adult women with
      classical congenital adrenal hyperplasia.
AB  - CONTEXT: Concern has been raised regarding the potential impact of chronic
      glucocorticoid therapy on the bone mineral density (BMD) of patients with
      congenital adrenal hyperplasia (CAH). OBJECTIVE: The purpose of this
      investigation was to assess the impact of chronic glucocorticoid replacement in
      adult women with classical CAH. PATIENTS AND DESIGN: We used dual energy x-ray
      absorptiometry to evaluate lumbar spine and whole body BMD in 11 women with salt
      losing (SL) CAH and 15 with the simple virilizing form. Physical characteristics
      and serum hormone concentrations were also measured. Results were compared with
      those of unaffected sisters of CAH patients (n = 9). MAIN OUTCOME MEASURE: BMD
      was the main outcome measure. RESULTS: Osteopenia was noted in 45% of SL CAH
      patients, 13% of patients with the simple virilizing form, and 11% of controls.
      Lumbar spine and whole body BMDs of CAH subjects were lower than those of
      controls (P < 0.05). Compared with CAH subjects with normal BMD, those with
      osteopenia had reduced serum levels of dehydroepiandrosterone sulfate and
      dehydroepiandrosterone. Adrenal androgen levels were particularly suppressed
      among postmenopausal women receiving glucocorticoid replacement. CONCLUSIONS:
      Adult women with classical CAH treated with long-term glucocorticoids are at risk
      for decreased BMD, especially those with the SL form. Oversuppression of adrenal
      androgens is associated with increased risk for bone loss in this population.

PMID- 16278271
TI  - Clinical and immunogenetic characteristics of fulminant type 1 diabetes
      associated with pregnancy.
AB  - OBJECTIVE: The objective of this study was to characterize the clinical and
      immunogenetic features of Japanese pregnancy-associated fulminant type 1 diabetes
      (PF). A group of patients with PF was compared with a group of patients of child
      bearing age with fulminant type 1 diabetes that was not associated with pregnancy
      (NPF) in a nationwide survey conducted from 2000-2004. PATIENTS: The clinical
      characteristics of the 22 patients in the PF group were compared with those of
      the 48 patients in the NPF group. Human leukocyte antigen (HLA) class II DR and
      DQ genotyping of 17 PF and 20 NPF patients was performed. RESULTS: Arterial pH
      was significantly lower (P = 0.0366), and amylase values tended to increase in PF
      patients compared with NPF patients (P = 0.0515). In 22 PF patients, 18 developed
      disease during pregnancy (26.3 wk; range, 7-38), whereas four cases occurred
      immediately after delivery (10.5 d; range, 7-14 d). Twelve cases that developed
      during pregnancy resulted in stillbirth (67%), and five of the six fetal cases
      that survived were delivered by cesarean section. The haplotype frequency of HLA
      DRB1*0901-DQB1*0303 in PF was significantly higher than those in NPF (P = 0.0244)
      and controls (P = 0.0001), whereas that of DRB1*0405-DQB1*0401 in NPF was
      significantly higher than those in PF (P = 0.0162) and controls (P < 0.0001).
      CONCLUSIONS: The clinical symptoms of PF patients were more severe than those of
      NPF patients, and the prognosis of their fetuses was extremely poor. The type 1
      diabetes-susceptible HLA class II haplotype is distinct in PF and NPF patients,
      suggesting that different HLA haplotypes underlie the presentation of PF or NPF.

PMID- 16278272
TI  - Role of atrial septostomy in the treatment of children with pulmonary arterial
      hypertension.
AB  - OBJECTIVES: To assess in retrospect the safety and effectiveness of atrial
      septostomy in children with severe pulmonary arterial hypertension without an
      intracardiac communication. METHODS: 20 patients were reviewed retrospectively,
      19 with idiopathic pulmonary arterial hypertension. The mean age at septostomy
      was 8.4 years (range 3 months to 17 years). Graded balloon septostomy alone was
      carried out in eight patients, a blade septostomy was done in two, a blade
      septostomy plus graded balloon septostomy was done in three, and a fenestrated
      device was inserted in seven. RESULTS: There were no fatalities. Four children
      suffered complications during the procedure. None had further syncope and all
      improved symptomatically with a significant (p < 0.01) decrease in World Health
      Organization functional class (mean shift -0.6) and a significant improvement in
      the semiquantitative echocardiographic assessment of right ventricular function
      (p < 0.03). The mean oxygen saturation decreased by 7.8 percentage points. The
      atrial communication closed in two children, necessitating a repeat procedure.
      After a mean follow up of 2.1 years (range one month to 6.7 years), 18 of 20
      children are still alive. CONCLUSION: Atrial septostomy improved symptoms and
      quality of life in a group of children deteriorating with severe pulmonary
      arterial hypertension. This procedure is to be recommended for severely
      symptomatic children, before they become critically ill. Fenestrated devices may
      help ensure indefinite patency of the atrial communication.

PMID- 16278273
TI  - Increased periconceptual maternal glycated haemoglobin in diabetic mothers
      reduces fetal long axis cardiac function.
AB  - OBJECTIVE: To compare ventricular long axis function in fetuses of diabetic
      mothers (FDM) with contemporaneously studied normal controls (N) and to assess
      the effect of pre-pregnancy diabetic control on these measurements. DESIGN: Long
      axis function was compared in 41 FDM and 159 N fetuses in a cross sectional
      observational study. SETTING: Fetal medicine unit. METHODS AND RESULTS:
      Echocardiography confirmed structural normality. Pulsed wave valvar Doppler
      velocimetry, lengthening and shortening myocardial velocities, and amplitude of
      ventricular long axis movement were recorded at the base of the left and right
      ventricular free walls and septum. Periconceptual diabetic control was assessed
      by haemoglobin A1c (HbA1c) in early pregnancy. Doppler and myocardial velocities
      were negatively related and myocardial thickness was positively related with
      HbA1c. In both cohorts all variables except mitral and tricuspid late filling (A
      wave) velocities were dependent on gestational age. FDM gestational age related
      values were higher for most variables and robust analysis of covariance showed
      significantly different maturation patterns in mitral valve E:A ratio (p = 0.036)
      and pulmonary velocity (p = 0.04), late lengthening myocardial velocities (left p
      = 0.016 and right p = 0.066), left myocardial shortening velocities (p = 0.008),
      and left free wall (p = 0.03) and septal (p = 0.04) amplitude of motion. FDM
      septal thickness was significantly increased throughout gestation (p < 0.0001).
      CONCLUSION: Periconceptual diabetic control influences fetal cardiac performance
      and myocardial hypertrophy but, unlike the pathophysiology of adult ventricular
      hypertrophy, is accompanied by functional adaptation. It is unlikely to explain
      the increased rate of late stillbirth observed in diabetic pregnancies.

PMID- 16278274
TI  - Pulmonary vein stenosis: initial experience with cutting balloon angioplasty.
AB  - OBJECTIVE: To determine the safety and effectiveness of cutting balloon
      angioplasty for pulmonary vein stenosis (PVS). DESIGN AND SETTING: Retrospective
      review of case notes and cardiac catheterisation data at the Royal Brompton
      Hospital. MAIN OUTCOME MEASURES: Diameter of pulmonary vein, tricuspid
      regurgitant jet velocity on echocardiogram, and percutaneous oxygen saturation
      before and after cutting balloon angioplasty. RESULTS: Three patients had
      congenital PVS and three had PVS associated with total anomalous pulmonary venous
      drainage. A total of 27 PVSs were treated during 12 catheterisation procedures.
      Median patient age at the time of procedure was 12.5 months (range 1.5-36 months)
      and weight was 7.1 kg (range 2.8-11.1 kg). Minimum pulmonary vein diameter
      increased significantly on angiography after cutting balloon angioplasty, from
      mean (SD) 2.3 (0.7) mm to 4.2 (1.9) mm, mean of differences 1.9 mm (95%
      confidence interval (CI) 0.9 to 2.9 mm, p = 0.0013). Mean (SD) oxygen saturation
      rose from 79.6 (12.9)% to 83.9 (9.0)%, mean of differences 4.3% (95% CI 0.7% to
      8.0%, p = 0.0238). All children's symptoms improved subjectively. Tricuspid
      regurgitant jet velocity did not change significantly. The longest time interval
      before repeat intervention was six months. There were no acute deaths; one
      patient had a small pulmonary haemorrhage and developed a small aneurysm adjacent
      to the site of angioplasty. CONCLUSION: Cutting balloon angioplasty is safe in
      the palliation of PVS in children. It gives some acute relief but often needs to
      be repeated, as improvement is rarely sustained.

PMID- 16278275
TI  - Can atrioventricular septal defects exist with intact septal structures?
AB  - The hallmark of an atrioventricular septal defect (AVSD) is a common
      atrioventricular junction, giving rise to a trileaflet left atrioventricular
      valve. AVSDs have the potential for interatrial shunting alone, interventricular
      shunting alone, or both. AVSDs without interatrial or interventricular
      communications have been identified at postmortem examination, but there are no
      reports of AVSDs with intact septal structures diagnosed in life. Six patients
      are described with AVSD and intact atrial and ventricular septa diagnosed
      echocardiographically. This report shows that AVSDs can exist without interatrial
      or interventricular communications and that the characteristic feature of this
      condition, the common atrioventricular junction with a trileaflet left
      atrioventricular valve, can be diagnosed in life by using cross sectional
      echocardiography. AVSDs with intact septal structures may be more common than
      previously described.

PMID- 16278276
TI  - Effects of sodium nitrite on ischemia-reperfusion injury in the rat kidney.
AB  - Reactive oxygen and nitrogen species play a key role in the pathophysiology of
      renal ischemia-reperfusion (I/R) injury. Recent studies have shown that nitrite
      (NO(2)(-)) serves as an endogenous source of nitric oxide (NO), particularly in
      the presence of hypoxia and acidosis. Nanomolar concentrations of NO(2)(-) reduce
      injury following I/R in the liver and heart in vivo. The purpose of this study
      was to evaluate the role of NO(2)(-) in renal I/R injury. Male Sprague-Dawley
      rats underwent a unilateral nephrectomy followed by 45 min of ischemia of the
      contralateral kidney or sham surgery under isoflurane anesthesia. Animals
      received normal saline, sodium NO(2)(-), or sodium nitrate (NO(3)(-); 1.2 nmol/g
      body wt ip) at 22.5 min after induction of ischemia or 15 min before ischemia. A
      separate set of animals received saline, NO(2)(-), or NO(3)(-) (0.12, 1.2, or 12
      nmol/g body wt iv) 45 min before ischemia. Serum creatinine and blood urea
      nitrogen were increased following I/R injury but were not significantly different
      among treatment groups at 24 and 48 h after acute renal injury. Interestingly,
      NO(3)(-) administration appeared to worsen renal injury. Histological scoring for
      loss of brush border, tubular necrosis, and red blood cell extravasation showed
      no significant differences among the treatment groups. The results indicate that,
      contrary to the protective effects of NO(2)(-) in I/R injury of the liver and
      heart, NO(2)(-) does not provide protection in renal I/R injury and suggest a
      unique metabolism of NO(2)(-) in the kidney.

PMID- 16278277
TI  - SMP-534 ameliorates progression of glomerular fibrosis and urinary albumin in
      diabetic db/db mice.
AB  - Diabetic nephropathy is currently the most common cause of end-stage renal
      disease. Diabetic nephropathy patients, whether insulin dependent or not, develop
      fibrotic changes in glomeruli that manifest as overt nephropathy. Previously, we
      demonstrated that 5-chloro-2-{(1E)-3-[2-(4-methoxybenzoyl)-4-methyl-1H-pyrrol-1
      yl]prop-1-en-1-yl}-N-(methylsulfonyl)benzamide (SMP-534) reduces extracellular
      matrix (ECM) production induced by transforming growth factor-beta (TGF-beta) in
      vitro and prevents the accumulation of ECM in glomeruli in rat Thy-1 nephritis
      models. In this study, we examined the long-term effects of SMP-534 on renal
      insufficiency and glomerulosclerosis in db/db mice, which are models of type 2
      diabetes. A diet containing SMP-534 was given to the mice from the age of 9 to 25
      wk, and blood and urine analysis were performed at 8, 17, and 25 wk. At the end
      of study, kidney tissues were analyzed histologically. Treatment with SMP-534
      dose dependently suppressed the increase of urinary albumin and type IV collagen
      excretion in db/db mice. The renal histological analysis showed that SMP-534 dose
      dependently suppressed the increase of mesangial expansion in the kidney. In the
      immunohistological analysis, fibronectin and type IV collagen expression were
      lower in SMP-534-treated db/db mice compared with vehicle-treated db/db mice.
      This study suggested that SMP-534 ameliorated the increase of ECM production in
      kidney of db/db mice, possibly through the inhibition of TGF-beta action. Hence,
      antifibrotic agents such as SMP-534 might be a new therapeutic option for the
      treatment of diabetic nephropathy.

PMID- 16278278
TI  - Alternative splicing generates a smaller assortment of CaV2.1 transcripts in
      cerebellar Purkinje cells than in the cerebellum.
AB  - P/Q-type calcium channels control many calcium-driven functions in the brain. The
      CACNA1A gene encoding the pore-forming CaV2.1 (alpha1A) subunit of P/Q-type
      channels undergoes alternative splicing at multiple loci. This results in channel
      variants with different phenotypes. However, the combinatorial patterns of
      alternative splice events at two or more loci, and hence the diversity of CaV2.1
      transcripts, are incompletely defined for specific brain regions and types of
      brain neurons. Using RT-PCR and splice variant-specific primers, we have
      identified multiple CaV2.1 transcript variants defined by different pairs of
      splice events in the cerebellum of adult rat. We have uncovered new splice
      variations between exons 28 and 34 (some of which predict a premature stop codon)
      and a new variation in exon 47 (which predicts a novel extended COOH-terminus).
      Single cell RT-PCR reveals that each individual cerebellar Purkinje neuron also
      expresses multiple alternative CaV2.1 transcripts, but the assortment is smaller
      than in the cerebellum. Two of these variants encode different extended COOH
      termini which are not the same as those previously reported in Purkinje cells of
      the mouse. Our patch-clamp recordings show that calcium channel currents in the
      soma and dendrites of Purkinje cells are largely inhibited by a concentration of
      omega-agatoxin IVA selective for P-type over Q-type channels, suggesting that the
      different transcripts may form phenotypic variants of P-type calcium channels in
      Purkinje cells. These results expand the known diversity of CaV2.1 transcripts in
      cerebellar Purkinje cells, and propose the selective expression of distinct
      assortments of CaV2.1 transcripts in different brain neurons and species.

PMID- 16278279
TI  - Gene expression profiling of gastrin target genes in parietal cells.
AB  - Previous studies demonstrated that mice with a null mutation in the gene encoding
      the hormone gastrin have impaired gastric acid secretion. Hence, the aim of this
      study was to evaluate changes in the acid-secreting parietal cell in gastrin
      deficient (GAS-KO) mice. Analysis of several transcripts encoding parietal cell
      proteins involved in gastric acid secretion showed reduced abundance in the GAS
      KO stomach, including H+,K+-ATPase alpha- and beta-subunits, KCNQ1 potassium
      channel, aquaporin-4 water channel, and creatine kinase B, which were reversed by
      gastrin infusion for 1 wk. Although mRNA and protein levels of LIM and SH3 domain
      containing protein-1 (LASP-1) were not greatly changed in the mutant, there was a
      marked reduction in phosphorylation, consistent with its proposed role as a cAMP
      signal adaptor protein associated with acid secretion. A more comprehensive
      analysis of parietal cell gene expression in GAS-KO mice was performed using the
      Affymetrix U74AV2 chip with RNA from parietal cells purified by flow cytometry to
      >90%. Comparison of gene expression in GAS-KO and wild-type mice identified 47
      transcripts that differed by greater than or equal to twofold, suggesting that
      gastrin affects parietal cell gene expression in a specific manner. The
      differentially expressed genes included several genes in signaling pathways, with
      a substantial number (20%) known to be target genes for Wnt and Myc.

PMID- 16278280
TI  - Dynamic postural balance in ankylosing spondylitis patients.
AB  - OBJECTIVES: In this study, our objectives were to investigate whether patients
      with ankylosing spondylitis (AS) have a poorer dynamic balance than normal
      subjects, and to study the relationship between balance and posture. METHODS:
      Seventy patients (57 men, 13 women) with AS and 35 (31 men, 4 women) controls
      matched for age, weight, height and body mass index were tested using the Biodex
      Stability System. Anteroposterior (AP), mediolateral (ML) and overall (OA)
      indices were obtained with bilateral stance at platform stabilities of 8 and 4.
      Subjects were tested with 'eyes open' at all times. Correlation analyses were
      performed between stability indices (OA, AP, ML) and disease duration, cervical
      rotation (CR), tragus to wall distance (TWD), lumbar side flexion (LSF), lumbar
      flexion (LF), intermalleolar distance (IMD) and Bath Ankylosing Spondylitis
      Metrology Index (BASMI) total score. RESULTS: No significant difference was found
      between the AS patients and healthy subjects with respect to all three stability
      indices at levels 4 and 8. A positive correlation was found only between ML
      stability index and TWD at level 8 (r, 0.249; P = 0.038). No other positive
      correlation was detected between stability indices and CR, TWD, LSF, LF, IMD,
      total BASMI score and disease duration. CONCLUSIONS: AS has no negative effect on
      postural stability. The only clinically significant association was found between
      dynamic postural balance and TWD.

PMID- 16278281
TI  - A critical review of foot orthoses in the rheumatoid arthritic foot.
AB  - Foot orthoses are commonly prescribed by health professionals as a form of
      intervention for the symptomatic foot in rheumatoid arthritis. However, there is
      a limited evidence base to support the use of foot orthoses in this patient
      group. This article provides a critical review of the use of foot orthoses in the
      management of rheumatoid arthritic foot pathologies. A search was conducted in
      the Cochrane Controlled Trials Register (current issue of the Cochrane Library),
      Physiotherapy evidence database (PEDro), Medline, The Cumulative Index to Nursing
      and Allied Health Literature (CINAHL) and Allied and Complementary Medicine
      (AMED) and from reference lists in journal articles. The language was restricted
      to English. Searching of the databases was undertaken between December 2004 and
      March 2005. The results indicated there is no consensus of opinion on the choice
      of foot orthoses used for the management of pathology in the rheumatoid foot,
      although there is strong evidence that foot orthoses do reduce pain and improve
      functional ability. The type of foot orthoses used ranged from simple cushioned
      insoles to custom-made rigid cast devices. Methodological issues raised included
      small sample size and poor use of valid and reliable outcome measures. There is
      limited evidence pertaining to cost-effectiveness. The results indicated a need
      for further investigation into the most clinically and cost-effective foot
      orthoses to prescribe in the management of the rheumatoid arthritic foot. This
      review highlights the need to identify the various types of foot orthoses that
      are most effective in the management of the established rheumatoid arthritic
      foot.

PMID- 16278282
TI  - Chondroprotective drugs in degenerative joint diseases.
AB  - Catabolic cytokine and anabolic growth factor pathways control destruction and
      repair in osteoarthritis (OA). A unidirectional TNF-alpha/IL-1-driven cytokine
      cascade disturbs the homeostasis of the extracellular matrix of articular
      cartilage in OA. Although chondrocytes in OA cartilage overexpress anabolic
      insulin-like growth factor (IGF) and its specific receptor (IGFRI) autocrine TNF
      alpha released by apoptotic articular cartilage cells sets off an auto/paracrine
      IL-1-driven cascade that overrules the growth factor activities that sustain
      repair in degenerative joint disease. Chondroprotection with reappearance of a
      joint space that had disappeared has been documented unmistakably in peripheral
      joints of patients suffering from spondyloarthropathy when treated with TNF-alpha
      blocking agents that repressed the unidirectional TNF-alpha/IL-1-driven cytokine
      cascade. A series of connective tissue structure-modifying agents (CTSMAs) that
      directly affect IL-1 synthesis and release in vitro and down-modulate downstream
      IL-1 features, e.g. collagenase, proteoglycanase and matrix metalloproteinase
      activities, the expression of inducible nitric oxide synthase, the increased
      release of nitric oxide, and the secretion of prostaglandin E(2), IL-6 and IL-8,
      have been shown to possess disease-modifying OA drug (DMOAD) activities in
      experimental models of OA and in human subjects with finger joint and knee OA.
      Examples are corticosteroids, some sulphated polysaccharides, chemically modified
      tetracyclines, diacetylrhein/rhein, glucosamine and avocado/soybean
      unsaponifiables.

PMID- 16278284
TI  - Devic's syndrome in systemic lupus erythematosus and probable antiphospholipid
      syndrome.

PMID- 16278285
TI  - Clinical significance of serum levels of matrix metalloproteinase-13 in patients
      with systemic sclerosis.
AB  - OBJECTIVES: To investigate the clinical significance of serum matrix
      metalloproteinase-13 (MMP-13) levels in patients with systemic sclerosis (SSc).
      METHODS: Serum MMP-13 levels were determined by using a peptide substrate
      cleavage assay in 20 patients with diffuse cutaneous SSc (dcSSc), 20 with limited
      cutaneous SSc (lcSSc) and 10 normal controls. RESULTS: The serum MMP-13 levels in
      patients with dcSSc or lcSSc were significantly lower than those in normal
      controls (53.4 +/- 14.1 vs 73.2 +/- 11.5 ng/ml, P < 0.0005; 59.4 +/- 14.8 vs 73.2
      +/- 11.5 ng/ml, P < 0.005, respectively), but there was no significant difference
      in the serum MMP-13 levels between patients with dcSSc and those with lcSSc.
      Disease duration prior to the diagnosis was significantly shorter in SSc patients
      with decreased serum MMP-13 levels than in those with normal levels (3.0 +/- 2.2
      vs 8.6 +/- 7.6 yr, P < 0.0005). In addition, serum MMP-13 levels were moderately
      correlated with the duration of the disease (r = 0.451, P < 0.05). Though there
      was no significant difference in the frequencies of pulmonary fibrosis or reduced
      %DLco (diffusing capacity of lung for carbon monoxide), the frequency of reduced
      %VC (vital capacity) was significantly greater in patients with decreased serum
      MMP-13 levels than in those with normal levels (73 vs 24%, P < 0.05).
      CONCLUSIONS: Matrix metalloproteinase-13 may be involved in the fibrotic process
      of SSc, especially in the initiation of fibrosis. The serum MMP-13 levels may
      serve as a useful marker for the severity of pulmonary fibrosis in patients with
      SSc.

PMID- 16278286
TI  - Genome scan meta-analysis of rheumatoid arthritis.
AB  - OBJECTIVE: Genome scans for rheumatoid arthritis (RA) have yielded inconsistent
      results. The absence of replication of linkage might be due to lack of power of
      individual studies. We performed a genome scan meta-analysis of published data to
      increase statistical power and to assess evidence for linkage of RA across genome
      scan studies. METHODS: Four RA whole-genome scans containing 767 families with
      964 sibling pairs were included for the genome scan meta-analysis (GSMA). The
      GSMA method was applied to pool the results obtained from four genome scans. For
      each study, 120 genomic bins of approximately 30 centimorgans were defined and
      ranked according to maximum evidence for linkage within each bin. Bin ranks were
      weighted and summed across all studies. The summed rank for each bin was assessed
      empirically for significance using permutation methods. RESULTS: A total of nine
      bins lay above the 95% confidence level (P=0.05) and four bins were above the 99%
      confidence level (P=0.01) in the RA GSMA, suggesting that these bins contain RA
      linked loci: bins 6.2, 6.4, 8.1, 18.3, 12.3, 12.2, 1.5, 6.3 and 16.2. The
      strongest evidence for linkage occurred on chromosome 6p22.3-6p21.1 (bin 6.2),
      containing the HLA region (P(sumrnk)=0.0000008). CONCLUSION: This RA GSMA
      confirmed the evidence for HLA loci as the greatest susceptibility factor to RA
      and showed evidence for linkage at non-HLA loci, such as chromosomes 1p, 6, 8p,
      12, 16 and 18q, across studies. These data may provide a basis to carry out
      targeted linkage and candidate gene studies, particularly in the regions.

PMID- 16278287
TI  - The impact of anti-TNF-alpha therapy on the nature of service provision.

PMID- 16278288
TI  - Disease damage and low bone mineral density: an analysis of women with systemic
      lupus erythematosus ever and never receiving corticosteroids.
AB  - OBJECTIVES: To evaluate the relationship between disease damage and bone mineral
      density (BMD) in women with systemic lupus erythematosus (SLE). METHODS: A cross
      sectional study was conducted among 307 women with SLE. Patients attended a
      single clinic visit that included an interview, physical examination, laboratory
      testing and BMD measurements (hip and/or lumbar spine). Women were stratified by
      the Systemic Lupus International Collaborating Clinics/American College of
      Rheumatology cumulative disease damage index (SDI) > or =1 (Damage) vs SDI=0 (No
      Damage), and prior use of corticosteroids (CS), yielding four groups: (1)
      Damage/CS(+) (n=138), (2) Damage/CS(-) (n=23), (3) no Damage/CS(-) (n=100), and
      (4) no Damage/CS(-) (n=46). RESULTS: Mean age at SLE diagnosis was 32.7 +/- 11.8
      yr, 24.4% were African American, 65.0% were premenopausal, and mean SDI +/- S.D.
      was 1.3 +/- 1.8. In the unadjusted and adjusted models controlling for
      significant univariate risk factors for osteoporosis, the reference group (Group
      1) had significantly lower mean BMD T-scores at the hip and lumbar spine than
      groups having no disease damage (Groups 3 and 4) independent of CS use status.
      Similar hip and lumbar spine mean BMD T-scores were observed in women with
      disease damage with and without CS exposure (Groups 1 and 2). CONCLUSIONS: Women
      with SLE having disease damage and no CS use had BMD T-scores at the hip and
      lumbar spine similar to those of women with disease damage and prior CS use.
      These findings suggest an association between disease damage and lower BMD T
      scores in women with SLE.

PMID- 16278289
TI  - Overexpression of calbindin-D28K in hippocampal progenitor cells increases
      neuronal differentiation and neurite outgrowth.
AB  - Excitatory stimuli are known to be a potent regulator for induction of neuronal
      differentiation. Calbindin-D28K buffers intracellular Ca2+ and modifies synaptic
      functions in neurons. However, the effects of calbindin-D28K on the regulation of
      activity-induced neuronal differentiation and related biochemical modifications
      remain unsolved. In the present study, by a gain-of-function study with
      retroviral vector system and dicer-generated small interfering RNA (d-siRNA) to
      effectively knock down the expression of calbindin-D28K, we demonstrated that
      calbindin-D28K at a physiologically relevant level promoted neuronal
      differentiation and neurite outgrowth. Increase of neuronal differentiation by
      calbindin-D28K overexpression was concurrent with the expression of basic helix
      loop-helix (bHLH) transcriptional factors, phosphorylation of calcium and
      calmodulin-dependent protein kinase II (CaMKII) and NeuroD at Ser(336). KN-62, a
      highly specific CaMKII inhibitor, blocked the up-regulation of proneural bHLH
      genes, p-CaMKII, and pSer(336)NeuroD. Calbindin-D28K appeared to facilitate
      neuronal differentiation of both fetal and adult hippocampal progenitor cells.
      Together, these findings establish the novel calbindin-regulated function of
      CaMKII and NeuroD in control of neuronal differentiation and neurite outgrowth.

PMID- 16278290
TI  - Capsaicin-sensitive sensory neurons regulate myocardial function and gene
      expression pattern of rat hearts: a DNA microarray study.
AB  - We have previously shown that capsaicin-sensitive sensory nerves contribute to
      the regulation of normal cardiac function and to the development of cardiac
      adaptation to ischemic stress; however, the underlying molecular mechanisms
      remain unknown. Therefore, here we assessed cardiac functional alterations and
      relative gene expression changes by DNA microarray analysis of 6400 genes in rat
      hearts 7 days after the end of systemic capsaicin treatment protocol leading to
      selective sensory chemodenervation. Capsaicin pretreatment resulted in a cardiac
      dysfunction characterized by elevation of left ventricular end-diastolic pressure
      and led to altered expression of 80 genes of known function or homology to known
      sequences. Forty-seven genes exhibited significant up-regulation and 33 genes
      were down-regulated (changes ranged from -3.9 to +4.8-fold). The expression
      changes of 10 selected genes were verified, and an additional 11 genes were
      examined by real-time quantitative PCR. This is the first demonstration that gene
      expression changes in the heart due to capsaicin pretreatment included vanilloid
      receptor-1 (capsaicin receptor), transient receptor potential protein, GABA
      receptor rho-3 subunit, 5-hydroxytryptamine 3 receptor B, neurokinin receptor 2,
      endothelial nitric oxide synthase, matrix metalloproteinase-13, cytochrome P450,
      farnesyl-transferase, ApoB, and leptin. None of the genes have been previously
      shown to be involved in the mechanism of the cardiac functional effects of
      sensory chemodenervation by capsaicin. We conclude that capsaicin-sensitive
      sensory nerves play a significant role in the regulation of a variety of neuronal
      and non-neuronal genes in the heart and possibly in other tissues as well.

PMID- 16278291
TI  - Dihydrosphingosine 1-phosphate stimulates MMP1 gene expression via activation of
      ERK1/2-Ets1 pathway in human fibroblasts.
AB  - Sphingosine kinase (SphK) is a conserved lipid kinase that catalyzes formation of
      important regulators of inter- and intracellular signaling, sphingosine-1
      phosphate (S1P), and dihydrosphingosine 1-phosphate (dhS1P). In this study, we
      investigated the role of SphK1 in the regulation of expression of matrix
      metalloproteinase 1 (MMP1) in dermal fibroblasts, a key event in regulation of
      extra cellular matrix. We show that overexpression of SphK1 up-regulated MMP1
      protein, MMP1 mRNA, and MMP1 promoter activity, and this action of SphK1 required
      activation of the ERK1/2-Ets1 and NF-kappaB pathways. Furthermore, experiments
      using SphK1 specific siRNA demonstrated that SphK1 is required for the TNF-alpha
      stimulation of MMP1. Additional data revealed a specific role of dhS1P, and not
      S1P, as a mediator of SphK1-dependent activation of ERK1/2 and up-regulation of
      MMP1. The stimulatory effect of dhS1P was sensitive to pertussis toxin,
      suggesting a possible involvement of a G-protein-coupled receptor. In contrast,
      S1P, but not dhS1P, stimulated the induction of COX-2, which demonstrated
      selective actions of these two closely related bioactive lipids. In conclusion,
      this study describes a novel mode of SphK1 signaling through generation of dhS1P
      with a key role in mediating transcriptional responses to TNF-alpha. This is the
      first report of selective function of dhS1P as compared with the better studied
      S1P.

PMID- 16278292
TI  - In smooth muscle, FK506-binding protein modulates IP3 receptor-evoked Ca2+
      release by mTOR and calcineurin.
AB  - Ca2+ release from the sarcoplasmic reticulum (SR) by the IP3 receptors (IP3Rs)
      crucially regulates diverse cell signalling processes from reproduction to
      apoptosis. Release from the IP3R may be modulated by endogenous proteins
      associated with the receptor, such as the 12 kDa FK506-binding protein (FKBP12),
      either directly or indirectly by inhibition of the phosphatase calcineurin. Here,
      we report that, in addition to calcineurin, FKPBs modulate release through the
      mammalian target of rapamycin (mTOR), a kinase that potentiates Ca2+ release from
      the IP3R in smooth muscle. The presence of FKBP12 was confirmed in colonic
      myocytes and co-immunoprecipitated with the IP3R. In aortic smooth muscle,
      however, although present, FKBP12 did not co-immunoprecipitate with IP3R. In
      voltage-clamped single colonic myocytes rapamycin, which together with FKBP12
      inhibits mTOR (but not calcineurin), decreased the rise in cytosolic Ca2+
      concentration ([Ca2+]c) evoked by IP3R activation (by photolysis of caged IP3),
      without decreasing the SR luminal Ca2+ concentration ([Ca2+]l) as did the mTOR
      inhibitors RAD001 and LY294002. However, FK506, which with FKBP12 inhibits
      calcineurin (but not mTOR), potentiated the IP3-evoked [Ca2+]c increase. This
      potentiation was due to the inhibition of calcineurin; it was mimicked by the
      phosphatase inhibitors cypermethrin and okadaic acid. The latter two inhibitors
      also prevented the FK506-evoked increase as did a calcineurin inhibitory peptide
      (CiP). In aortic smooth muscle, where FKBP12 was not associated with IP3R, the
      IP3-mediated Ca2+ release was unaffected by FK506 or rapamycin. Together, these
      results suggest that FKBP12 has little direct effect on IP3-mediated Ca2+
      release, even though it is associated with IP3R in colonic myocytes. However,
      FKBP12 might indirectly modulate Ca2+ release through two effector proteins: (1)
      mTOR, which potentiates and (2) calcineurin, which inhibits Ca2+ release from
      IP3R in smooth muscle.

PMID- 16278293
TI  - Three distinct chromatin domains in telomere ends of polytene chromosomes in
      Drosophila melanogaster Tel mutants.
AB  - Drosophila melanogaster telomeric DNA is known to comprise two domains: the
      terminal tract of retrotransposons (HeT-A, TART and TAHRE) and telomere
      associated sequences (TAS). Chromosome tips are capped by a protein complex,
      which is assembled on the chromosome ends independently of the underlying
      terminal DNA sequences. To investigate the properties of these domains in
      salivary gland polytene chromosomes, we made use of Tel mutants. Telomeres in
      this background are elongated owing to the amplification of a block of terminal
      retroelements. Supercompact heterochromatin is absent from the telomeres of
      polytene chromosomes: electron microscopy analysis identifies the telomeric cap
      and the tract of retroelements as a reticular material, having no discernible
      banding pattern, whereas TAS repeats appear as faint bands. According to the
      pattern of bound proteins, the cap, tract of retroelements and TAS constitute
      distinct and non-overlapping domains in telomeres. SUUR, HP2, SU(VAR)3-7 and
      H3Me3K27 localize to the cap region, as has been demonstrated for HP1. All these
      proteins are also found in pericentric heterochromatin. The tract of
      retroelements is associated with proteins characteristic for both heterochromatin
      (H3Me3K9) and euchromatin (H3Me3K4, JIL-1, Z4). The TAS region is enriched for
      H3Me3K27. PC and E(Z) are detected both in TAS and many intercalary
      heterochromatin regions. Telomeres complete replication earlier than
      heterochromatic regions. The frequency of telomeric associations in salivary
      gland polytene chromosomes does not depend on the SuUR gene dosage, rather it
      appears to be defined by the telomere length.

PMID- 16278294
TI  - The insulin-PI3K/TOR pathway induces a HIF-dependent transcriptional response in
      Drosophila by promoting nuclear localization of HIF-alpha/Sima.
AB  - The hypoxia-inducible factor (HIF) is a heterodimeric transcription factor
      composed of a constitutively expressed HIF-beta subunit and an oxygen-regulated
      HIF-alpha subunit. We have previously defined a hypoxia-inducible transcriptional
      response in Drosophila melanogaster that is homologous to the mammalian HIF
      dependent response. In Drosophila, the bHLH-PAS proteins Similar (Sima) and Tango
      (Tgo) are the functional homologues of the mammalian HIF-alpha and HIF-beta
      subunits, respectively. HIF-alpha/Sima is regulated by oxygen at several
      different levels that include protein stability and subcellular localization. We
      show here for the first time that insulin can activate HIF-dependent
      transcription, both in Drosophila S2 cells and in living Drosophila embryos.
      Using a pharmacological approach as well as RNA interference, we determined that
      the effect of insulin on HIF-dependent transcriptional induction is mediated by
      PI3K-AKT and TOR pathways. We demonstrate that stimulation of the transcriptional
      response involves upregulation of Sima protein but not sima mRNA. Finally, we
      have analyzed in vivo the effect of the activation of the PI3K-AKT pathway on the
      subcellular localization of Sima protein. Overexpression of dAKT and dPDK1 in
      normoxic embryos provoked a major increase in Sima nuclear localization,
      mimicking the effect of a hypoxic treatment. A similar increase in Sima nuclear
      localization was observed in dPTEN homozygous mutant embryos, confirming that
      activation of the PI3K-AKT pathway promotes nuclear accumulation of Sima protein.
      We conclude that regulation of HIF-alpha/Sima by the PI3K-AKT-TOR pathway is a
      major conserved mode of regulation of the HIF-dependent transcriptional response
      in Drosophila.

PMID- 16278295
TI  - Identification of the sequence determinants mediating the nucleo-cytoplasmic
      shuttling of TIAR and TIA-1 RNA-binding proteins.
AB  - TIAR and TIA-1 are two closely related RNA-binding proteins which possess three
      RNA recognition motifs (RRMs) followed by an auxiliary region. These proteins are
      involved in several mechanisms of RNA metabolism, including alternative hnRNA
      splicing and regulation of mRNA translation. Here we characterize the subcellular
      localization of these proteins in somatic cells. We demonstrate that TIAR and TIA
      1 continuously shuttle between the cytoplasm and the nucleus and belong to the
      class of RNA-binding proteins whose nuclear import is transcription-dependent. We
      identified RRM2 and the first half of the auxiliary region as important
      determinants for TIAR and TIA-1 nuclear accumulation. In contrast, the nuclear
      export of TIAR and TIA-1 is mediated by RRM3. Both RRMs contribute to TIAR and
      TIA-1 nuclear accumulation or export by their RNA-binding capacity. Indeed,
      whereas mutations of the highly conserved RNP2 or RNP1 peptides in RRM2
      redistribute TIAR to the cytoplasm, similar modifications in RRM3 abolish TIAR
      nuclear export. Moreover, TIAR and TIA-1 nuclear accumulation is a Ran-GTP
      dependent pathway, in contrast to its nuclear export which is unaffected by Ran
      GTP depletion and which is independent of the major CRM1-exporting pathway. This
      study demonstrates the importance of TIAR and TIA-1 RNA-binding domains for their
      subcellular localization and provides the first evidence for distinct functions
      of TIAR and TIA-1 RRMs.

PMID- 16278296
TI  - The Parkin co-regulated gene product, PACRG, is an evolutionarily conserved
      axonemal protein that functions in outer-doublet microtubule morphogenesis.
AB  - Eukaryotic cilia and flagella are highly conserved structures composed of a
      canonical 9+2 microtubule axoneme. Comparative genomics of flagellated and non
      flagellated eukaryotes provides one way to identify new putative flagellar
      proteins. We identified the Parkin co-regulated gene, or PACRG, from such a
      screen. Male mice deficient in PACRG are sterile, but its function has been
      little explored. The flagellated protozoan parasite Trypanosoma brucei possesses
      two homologues of PACRG. We performed RNA interference knockdown experiments of
      the two genes independently and both together. Simultaneous ablation of both
      proteins produced slow growth and paralysis of the flagellum with consequent
      effects on organelle segregation. Moreover, using transmission electron
      microscopy, structural defects were seen in the axoneme, with microtubule
      doublets missing from the canonical 9+2 formation. The occurrence of missing
      doublets increased toward the distal end of the flagellum and sequential loss of
      doublets was observed along individual axonemes. GFP fusion proteins of both
      PACRG homologues localised along the full length of the axoneme. Our results
      provide the first evidence for PACRG function within the axoneme, where we
      suggest that PACRG acts to maintain functional stability of the axonemal outer
      doublets of both motile and sensory cilia and flagella.

PMID- 16278297
TI  - DCDC2 is associated with reading disability and modulates neuronal development in
      the brain.
AB  - DYX2 on 6p22 is the most replicated reading disability (RD) locus. By saturating
      a previously identified peak of association with single nucleotide polymorphism
      markers, we identified a large polymorphic deletion that encodes tandem repeats
      of putative brain-related transcription factor binding sites in intron 2 of
      DCDC2. Alleles of this compound repeat are in significant disequilibrium with
      multiple reading traits. RT-PCR data show that DCDC2 localizes to the regions of
      the brain where fluent reading occurs, and RNA interference studies show that
      down-regulation alters neuronal migration. The statistical and functional studies
      are complementary and are consistent with the latest clinical imaging data for
      RD. Thus, we propose that DCDC2 is a candidate gene for RD.

PMID- 16278298
TI  - Normal motor learning during pharmacological prevention of Purkinje cell long
      term depression.
AB  - Systemic delivery of (1R-1-benzo thiophen-5-yl-2[2-diethylamino)-ethoxy] ethanol
      hydrochloride (T-588) prevented long-term depression (LTD) of the parallel fiber
      (PF)-Purkinje cell (PC) synapse induced by conjunctive climbing fiber and PF
      stimulation in vivo. However, similar concentrations of T-588 in the brains of
      behaving mice and rats affected neither motor learning in the rotorod test nor
      the learning of motor timing during classical conditioning of the eyeblink
      reflex. Rats given doses of T-588 that prevented PF-PC LTD were as proficient as
      controls in learning to adapt the timing of their conditioned eyeblink response
      to a 150- or 350-ms change in the timing of the paradigm. The experiment
      indicates that PF-PC LTD under control of the climbing fibers is not required for
      general motor adaptation or the learning of response timing in two common models
      of motor learning for which the cerebellum has been implicated. Alternative
      mechanisms for motor timing and possible functions for LTD in protection from
      excitotoxicity are discussed.

PMID- 16278299
TI  - Purkinje cell long-term depression is prevented by T-588, a neuroprotective
      compound that reduces cytosolic calcium release from intracellular stores.
AB  - Long-term depression (LTD) of the parallel-fiber (PF) Purkinje synapse induced by
      four different experimental paradigms could be prevented in rat cerebellar slices
      by T-588, a neuroprotective compound. The paradigms consisted of pairing PF
      activation with climbing-fiber activation, direct depolarization, glutamic
      iontophoretic depolarization, or caffeine. In all cases, LTD was determined by
      patch-clamp recording of PF excitatory postsynaptic currents at the Purkinje cell
      somata. T-588 at 1 muM prevented the triggering of LTD reversibly and did not
      generate LTD on its own. Two-photon calcium-sensitive dye imaging demonstrated
      that T-588 reduces intracellular calcium concentration ([Ca(2+)](i)) increase by
      blocking calcium release from intracellular stores. Because [Ca(2+)](i) increase
      has been widely shown to trigger LTD and glutamate excitotoxicity, we propose
      that LTD may act as a neuroprotective mechanism. As such, LTD would serve to
      decrease glutamatergic-receptor sensitivity to limit deleterious [Ca(2+)](i)
      increase rather than to act as a mechanism for cerebellar learning.

PMID- 16278300
TI  - Correlated dynamics of consecutive residues reveal transient and cooperative
      unfolding of secondary structure in proteins.
AB  - Nuclear spin relaxation is a powerful method for studying molecular dynamics at
      atomic resolution. Recent methods development in biomolecular NMR spectroscopy
      has enabled detailed investigations of molecular dynamics that are critical for
      biological function, with prominent examples addressing allostery, enzyme
      catalysis, and protein folding. Dynamic processes with similar correlation times
      are often detected in multiple locations of the molecule, raising the question of
      whether the underlying motions are correlated (corresponding to concerted
      fluctuations involving many atoms distributed across extended regions of the
      molecule) or uncorrelated (corresponding to independent fluctuations involving
      few atoms in localized regions). Here, we have used (13)C(alpha)(i -
      1)/(13)C(alpha)(i) differential multiple-quantum spin relaxation to provide
      direct evidence for correlated dynamics of consecutive amino acid residues in the
      protein sequence. By monitoring overlapping pairs of residues (i - 1 and i, i and
      i + 1, etc.), we identified correlated motions that extend through continuous
      segments of the sequence. We detected significant correlated conformational
      transitions in the native state of the E140Q mutant of the calmodulin C-terminal
      domain. Previous work has shown that this domain exchanges between two major
      conformational states that resemble the functionally relevant open and closed
      states of the WT protein, with a mean correlation time of approximately 20
      micros. The present results reveal that an entire alpha-helix undergoes partial
      unraveling in a transient and cooperative manner.

PMID- 16278301
TI  - A rice-based edible vaccine expressing multiple T cell epitopes induces oral
      tolerance for inhibition of Th2-mediated IgE responses.
AB  - Peptide immunotherapy using multiple predominant allergen-specific T cell
      epitopes is a safe and promising strategy for the control of type I allergy. In
      this study, we developed transgenic rice plants expressing mouse dominant T cell
      epitope peptides of Cry j I and Cry j II allergens of Japanese cedar pollen as a
      fusion protein with the soybean seed storage protein glycinin. Under the control
      of the rice seed storage protein glutelin GluB-1 promoter, the fusion protein was
      specifically expressed and accumulated in seeds at a level of 0.5% of the total
      seed protein. Oral feeding to mice of transgenic rice seeds expressing the T cell
      epitope peptides of Cry j I and Cry j II before systemic challenge with total
      protein of cedar pollen inhibited the development of allergen-specific serum IgE
      and IgG antibody and CD4(+) T cell proliferative responses. The levels of
      allergen-specific CD4(+) T cell-derived allergy-associated T helper 2 cytokine
      production of IL-4, IL-5, and IL-13 and histamine release in serum were
      significantly decreased. Moreover, the development of pollen-induced clinical
      symptoms was inhibited in our experimental sneezing mouse model. These results
      indicate the potential of transgenic rice seeds in production and mucosal
      delivery of allergen-specific T cell epitope peptides for the induction of oral
      tolerance to pollen allergens.

PMID- 16278302
TI  - Beta-agonists modulate T-cell functions via direct actions on type 1 and type 2
      cells.
AB  - Although the beta2-adrenergic receptor (beta2AR) is the most extensively
      characterized G-protein-coupled receptor (GPCR), the effects of beta-agonists on
      T-cell subtype function remain poorly understood. In contrast to studies
      suggesting lack of beta2AR expression on type 2 T cells, we demonstrate that type
      2 interleukin-13+ (IL-13+) T cells (CD4+ or CD8+) in human peripheral blood
      lymphocytes (PBLs) can respond directly to beta-agonist, with effects including
      induction of protein kinase A (PKA) activity and associated inhibition of CD3
      stimulated CD25 expression; CD3-stimulated IL-13, interferon-gamma (IFN-gamma),
      and IL-2 production; and p38 mitogen-activated protein kinase (MAPK)
      phosphorylation. PGE2 was more efficacious than beta-agonist in activating PKA
      and inhibiting cytokine production. beta-agonist and PGE2 also inhibited phorbol
      myristate acetate (PMA) + calcimycin-stimulated IFN-gamma and IL-2 (but not IL
      13) production, suggesting that upstream CD3-initiated signaling is not the sole
      locus of PKA actions. Differential regulation of PMA-stimulated p38, p42/p44, and
      NF-kappaB explained the capacity of PGE2 and beta-agonist to inhibit IFN-gamma
      but not IL-13 production. The inhibition of CD3 + CD28-stimulated IL-13
      production by both beta-agonist and PGE2 was reversed at low agonist
      concentrations, resulting in enhanced IL-13, but not IFN-gamma or IL-2,
      production. These findings identify direct effects of beta2AR activation on T
      cell subtypes and suggest a complex role for GPCRs and PKA activity in modulating
      T-cell functions.

PMID- 16278303
TI  - Annexin 1 and its bioactive peptide inhibit neutrophil-endothelium interactions
      under flow: indication of distinct receptor involvement.
AB  - We have tested the effects of annexin 1 (ANXA1) and its N-terminal peptide Ac2-26
      on polymorphonuclear leukocyte (PMN) recruitment under flow. Differential effects
      of the full-length protein and its peptide were observed; ANXA1 inhibited firm
      adhesion of human PMNs, while Ac2-26 significantly attenuated capture and rolling
      without effect on firm adhesion. Analysis of the effects of ANXA1 and Ac2-26 on
      PMN adhesion molecule expression supported the flow chamber results, with Ac2-26
      but not ANXA1 causing l-selectin and PSGL-1 shedding. ANXA1 and its peptide act
      via the FPR family of receptors. This was corroborated using HEK-293 cells
      transfected with FPR or FPRL-1/ALX (the 2 members of this family expressed by
      human PMNs). While Ac2-26 bound both FPR and FPRL-1/ALX, ANXA1 bound FPRL-1/ALX
      only. ANXA1 and Ac2-26 acted as genuine agonists; Ac2-26 binding led to ERK
      activation in both FPR- and FPRL-1/ALX-transfected cells, while ANXA1 caused ERK
      activation only in cells transfected with FPRL-1/ALX. Finally, blockade of FPRL
      1/ALX with a neutralizing monoclonal antibody was found to abrogate the effects
      of ANXA1 in the flow chamber but was without effect on Ac2-26-mediated inhibition
      of rolling. These findings demonstrate for the first time distinct mechanisms of
      action for ANXA1 and its N-terminal peptide Ac2-26.

PMID- 16278304
TI  - Enhanced sensitivity to inhibition of SHP2, STAT5, and Gab2 expression in chronic
      myeloid leukemia (CML).
AB  - Although targeting the BCR-ABL tyrosine kinase activity by imatinib mesylate has
      rapidly become first-line therapy in chronic myeloid leukemia (CML), drug
      resistance suggests that combination therapy directed to a complementing target
      may significantly improve treatment results. To identify such potential targets,
      we used lentivirus-mediated RNA interference (RNAi) as a tool for functional
      genomics in cell lines as well as primary normal and CML CD34+ cells. In a
      conditional cell culture model, we demonstrate that RNAi-mediated reduction of
      SHP2, STAT5, and Gab2 protein expression inhibits BCR-ABL-dependent but not
      cytokine-dependent proliferation in a dose-dependent manner. Similarly, colony
      formation of purified primary CML but not of normal CD34+ colony-forming cells is
      specifically reduced by inhibition of SHP2, STAT5, and Gab2 expression,
      respectively. In addition, coexpression of both anti-BCR-ABL and anti-SHP2 shRNAs
      from a single lentiviral vector induces stronger inhibition of colony formation
      as compared to either shRNA alone. The data indicate that BCR-ABL expression may
      affect the function of normal signaling molecules. Targeting these molecules may
      harbor significant therapeutic potential for the treatment of patients with CML.

PMID- 16278305
TI  - A subset of human rapidly self-renewing marrow stromal cells preferentially
      engraft in mice.
AB  - Controversies have arisen as to whether adult stem cells or progenitor cells from
      bone marrow can engraft into nonhematopoietic tissues in vivo. To resolve some of
      the controversies, we developed a highly sensitive polymerase chain reaction
      based single nucleotide polymorphism (PCR-SNP) assay for competitive engraftment
      of mixtures of stem/progenitor cells. We used the assay to follow engraftment in
      immunodeficient mice of subpopulations of the stem/progenitor cells from human
      bone marrow referred to as either mesenchymal stem cells or marrow stromal cells
      (MSCs). The engraftment into adult mice without induced tissue injury was low and
      variable, but there was preferential engraftment of a subpopulation of rapidly
      self-renewing MSCs (RS-MSCs) compared with a subpopulation of slowly renewing
      MSCs (SR-MSCs). After intravenous infusion, there was a tendency for the cells to
      engraft into the hippocampal region that was previously designated a "vascular
      niche." Migration assays suggested that preferential engraftment of RS-MSCs was
      in part explained by their expression of CXCR4 and CX3R1, the receptors for SDF-1
      and fractalkine.

PMID- 16278306
TI  - Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic
      GvHD.
AB  - CD4+CD25+ regulatory T cells (Tregs) control immune responses to self- and
      foreign antigens and play a pivotal role in autoimmune diseases, infectious and
      noninfectious inflammation, and graft rejection. Since recent experimental
      studies have indicated that Tregs were able to ameliorate graft-versus-host
      disease (GvHD), we analyzed the number of infiltrating Tregs in the intestinal
      mucosa as one site of GvH reactivity using immunoenzymatic labeling to enumerate
      FOXP3+ T cells in 95 intestinal biopsies from 49 allografted patients in
      comparison with healthy controls and patients with infectious inflammation. While
      patients with cytomegalovirus (CMV)-colitis or diverticulitis showed a
      concomitant increase of CD8+ effectors and Tregs, acute and chronic GvHD were
      characterized by the complete lack of a counter-regulation indicated by a
      FOXP3+/CD8+ T-cell ratio identical to healthy controls. In contrast, specimens
      without histologic signs of GvHD demonstrated increased numbers of FOXP3+ per
      CD8+ T cells, indicating that the potential for Treg expansion is principally
      maintained in allografted patients. Our findings provide evidence that GvHD is
      associated with an insufficient up-regulation of Tregs in intestinal GvHD
      lesions. The determination of FOXP3+/CD8+ ratio can be a helpful tool to
      discriminate GvHD from infectious inflammation after allogeneic stem cell
      transplantation.

PMID- 16278307
TI  - Human embryonic stem cell-derived hematopoietic cells are capable of engrafting
      primary as well as secondary fetal sheep recipients.
AB  - The human/sheep xenograft model has proven valuable in assessing the in vivo
      hematopoietic activity of stem cells from a variety of fetal and postnatal human
      sources. CD34+/lineage- or CD34+/CD38- cells isolated from human embryonic stem
      cells (hESCs) differentiated on S17 feeder layer were transplanted by
      intraperitoneal injections into fetal sheep. Chimerism in primary transplants was
      established with polymerase chain reaction (PCR) and flow cytometry of bone
      marrow and peripheral blood samples. Whole bone marrow cells harvested from a
      primary recipient were transplanted into a secondary recipient. Chimerism was
      established as described before. This animal was stimulated with human GM-CSF,
      and an increase in human hematopoietic activity was noted by flow cytometry. Bone
      marrow aspirations cultured in methylcellulose generated colonies identified by
      PCR to be of human origin. We therefore conclude that hESCs are capable of
      generating hematopoietic cells that engraft primary recipients. These cells also
      fulfill the criteria for long-term engrafting hematopoietic stem cells as
      demonstrated by engraftment and differentiation in the secondary recipient.

PMID- 16278308
TI  - Tumor-derived lactic acid modulates dendritic cell activation and antigen
      expression.
AB  - The tumor milieu can influence dendritic cell (DC) differentiation. We analyzed
      DC differentiation in a 3-dimensional tumor model and propose a new mechanism of
      DC modulation by the tumor environment. Monocytes were cultured in the presence
      of IL-4 and GM-CSF within multicellular tumor spheroids (MCTSs) generated from
      different tumor cell lines. Monocytes invaded the MCTSs and differentiated into
      tumor-associated dendritic cells (TADCs). The antigen expression was altered on
      TADCs independent of the culture conditions (immature/mature DCs, Langerhans
      cells) and IL-12 secretion was reduced. Supernatants of MCTSs could partially
      transfer the suppressive effect. Conditioned media from urothelial carcinoma cell
      lines contained high levels of M-CSF and IL-6, both cytokines known to modulate
      DC differentiation. In contrast, melanoma and prostate carcinoma MCTS cocultures
      produced little M-CSF and IL-6, but high levels of lactic acid. Indeed, addition
      of lactic acid during DC differentiation in vitro induced a phenotype comparable
      with TADCs generated within melanoma and prostate carcinoma MCTSs. Blocking of
      lactic acid production in melanoma MCTS cocultures reverted the TADC phenotype to
      normal. We therefore conclude that tumor-derived lactic acid is an important
      factor modulating the DC phenotype in the tumor environment, which may critically
      contribute to tumor escape mechanisms.

PMID- 16278309
TI  - Hematopoiesis and stem cell renewal in long-term bone marrow cultures containing
      catalase.
AB  - Culturing mouse bone marrow in the presence of catalase dramatically alters
      hematopoiesis. Granulocyte output is initially increased 4- to 5-fold. This
      increase is transient and granulocyte production declines as immature (Sca-1+/LIN
      ) cells accumulate. One third of these immature cells have a phenotype (Sca-1+/c
      Kit+) characteristic of hematopoietic stem cells. At 2 to 3 weeks there are
      greater than 200-fold more Sca-1+/c-Kit+/LIN- cells in treated cultures than in
      controls. This population contains functional stem cells with both short-term and
      long-term bone marrow repopulating activity. In addition to myeloid progenitors,
      this Sca-1+/LIN- population contains a large number of cells that express CD31
      and CD34 and have an active Tie-2 promoter, indicating that they are in the
      endothelial lineage. After 3 to 4 weeks hematopoiesis in treated cultures wanes
      but if catalase is removed, hematopoiesis resumes. After 7 to 10 days the
      cultures are indistinguishable from untreated controls. Thus, protected from
      H2O2, hematopoietic progenitors multiply and become quiescent. This sequence
      resembles in vivo development in normal marrow. These results make it clear that
      peroxide-sensitive regulatory mechanisms play an important role in controlling
      hematopoiesis ex vivo and presumably in vivo as well. They also indicate that
      manipulation of the peroxide levels can be used to enhance the growth of
      hematopoietic stem cells in culture.

PMID- 16278311
TI  - Ex vivo imaging of fatty acid amide hydrolase activity and its inhibition in the
      mouse brain.
AB  - There is recent behavioral evidence that fatty acid amide hydrolase (FAAH)
      inhibitors produce a subset of cannabinoid receptor agonist effects, suggesting
      both anandamide-specific behavioral functions and possible regional differences
      in FAAH inhibitory effects. Here, we introduce a novel imaging method to quantify
      regional differences in brain FAAH activity. Upon intravenous [3H]anandamide
      administration, brain FAAH activity generates [3H]arachidonic acid, which is
      promptly trapped in membrane phospholipids. As a result, wild-type (WT) brains
      accumulate tritium in a regionally specific manner that is dependent upon
      regional FAAH activity, whereas brains from FAAH knockout (KO) mice show a
      uniform [3H]anandamide distribution. Increasing doses of anandamide +
      [3H]anandamide fail to alter regional tritium accumulation, suggesting
      insensitivity toward this process by anandamide-induced changes in regional
      cerebral blood flow. Regional tritiated metabolite levels in WT brains were
      highest in the somatosensory and visual cortices and the thalamus. Treatment with
      methylarachidonyl fluorophosphonate (MAFP) (1 mg/kg i.p.) reduced regional
      tritium accumulation in the somatosensory and visual cortices (p < 0.01), and at
      higher doses, the thalamus (p < 0.05). The selective FAAH inhibitor 1-oxazolo[4,5
      b]pyridin-2-yl-1-dodecanone (CAY10435), although having similar efficacy as MAFP
      in reducing tritium in the thalamus and somatosensory and visual cortices, also
      reduces caudate putamen and cerebellum (p < 0.01) activity. These data indicate
      FAAH activity generates heterogeneous regional accumulation of [3H]anandamide and
      metabolites, and they suggest the modulation of endocannabinoid tone by FAAH
      inhibitors depends upon not only the dose and compound used but also on the
      degree of FAAH expression in the brain regions examined. This imaging method
      determines regionally specific FAAH inhibition and can elucidate the in vivo
      effects of pharmacological agents targeting anandamide inactivation.

PMID- 16278310
TI  - Targeting receptor kinases by a novel indolinone derivative in multiple myeloma:
      abrogation of stroma-derived interleukin-6 secretion and induction of apoptosis
      in cytogenetically defined subgroups.
AB  - In multiple myeloma (MM), both vascular endothelial (VEGF) and basic fibroblast
      growth factor (bFGF) promote tumor growth and survival. We have used the novel
      indolinone BIBF 1000 to study effects of simultaneous inhibition of VEGF, FGF and
      transforming growth factor-beta on MM cells and their interactions with bone
      marrow stroma cells (BMSCs). Both, in the absence and presence of myeloma-stroma
      cell contacts, BIBF 1000 abrogated BMSC-derived secretion of interleukin-6 (IL
      6). In addition, BIBF 1000 directly induced apoptosis in t(4;14)-positive cell
      lines as well as in CD138+ marrow cells from patients with t(4;14) myeloma. To a
      similar extent, BIBF 1000 induced apoptosis in MM.1S and MM.1R cells carrying the
      translocation t(14;16). In case of MM.1S and other dexamethasone-sensitive
      t(14;16) cell lines, BIBF 1000 and dexamethasone had additive proapoptotic
      effects. Induction of apoptosis by BIBF 1000 was associated with inhibition of
      the mitogen-activated protein kinases (MAPK) pathway in t(4;14) and inhibition of
      the phosphatidyl-inositol-3 kinase/AKT pathway in t(14;16) cells. Apoptotic
      effects did not occur in t(4;14)-or t(14;16)-positive MM cells carrying n- or k
      Ras mutations. The data provide the rationale for clinical evaluation of this
      class of targeted kinase inhibitors in MM with focus on defined cytogenetic
      subgroups.

PMID- 16278313
TI  - Adenosine A1 receptor antagonist blunts urinary potassium excretion, but not
      renal hemodynamic effects, induced by carbonic anhydrase inhibitor in rats.
AB  - Acetazolamide (AZ) is a carbonic anhydrase inhibitor with diuretic actions at the
      proximal tubule. Clinical use of AZ is limited, in part, because of the urinary
      potassium loss and decrease of renal hemodynamic function that accompanies the
      drug. There is recent interest in A1 adenosine receptor (A1AR) antagonists, a
      novel class of diuretic agents that do not cause loss of potassium or
      tubuloglomerular feedback- (TGF) mediated reductions of renal hemodynamics. We
      tested whether the A1AR antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX)
      could attenuate the adverse effects normally associated with use of AZ. Renal
      blood flow (RBF) and urine output were measured during two consecutive 40-min
      periods in anesthetized rats. In the first period, vehicle or DPCPX was infused.
      DPCPX alone increased urine output and sodium excretion but did not significantly
      alter potassium output or RBF. In the second period, the initial infusion of
      vehicle or DPCPX was continued, and either AZ or its vehicle was administered. AZ
      alone increased urinary excretion of both sodium and potassium and decreased RBF.
      DPCPX significantly attenuated the AZ-induced increase of potassium excretion by
      50% but did not blunt the renal hemodynamic response to AZ. In a separate study,
      angiotensin II type 1 (AT1) receptor blockade also failed to blunt the renal
      hemodynamic response to AZ. In summary, A1AR antagonists may be useful diuretic
      agents alone or in combination with other conventional diuretic agents. The
      decrease of RBF that occurred in response to carbonic anhydrase inhibition was
      not attenuated by either A1AR blockade or AT1 receptor blockade and does not seem
      to be mediated by a TGF-dependent mechanism.

PMID- 16278312
TI  - Comparative evaluation of HERG currents and QT intervals following challenge with
      suspected torsadogenic and nontorsadogenic drugs.
AB  - The purpose of the present study was to comparatively evaluate human HERG
      currents and QT intervals following challenge with suspected torsadogenic and
      nontorsadogenic drugs. Various concentrations of 14 different drugs were
      initially evaluated in terms of their relative potency to block I(HERG) in stably
      transfected human embryonic kidney cells. Four general categories of drugs were
      identified: high-potency blockers (IC50 < 0.1 microM) included lidoflazine,
      terfenadine, and haloperidol; moderate-potency blockers (0.1 microM < IC50 < 1
      microM) included sertindole, thioridazine, and prenylamine; low-potency blockers
      (IC50 > 1 microM) included propafenone, loratadine, pyrilamine, lovastatin, and
      chlorpheniramine; and ineffective blockers (IC50 > 300 microM) included
      cimetidine, pentamidine, and arsenic trioxide. All measurements were performed
      using similar conditions and tested acute drug effects only (<30 min of drug
      exposure per measurement). Since two of the drugs that were ineffective I(HERG)
      blockers, arsenic trioxide and pentamidine, have been associated with cardiac
      repolarization delays (QT interval lengthening) and torsades de pointes
      ventricular arrhythmias in patients, we chose to evaluate them further using the
      isolated perfused rabbit heart model. Neither arsenic trioxide nor pentamidine
      had any significant effect on QT intervals in this model, even at relatively high
      (micromolar) concentrations. Similar results were obtained for loratadine in this
      model. When the hearts were challenged with a known torsadogenic drug such as
      cisapride, significant QT lengthening was rapidly induced. These results
      demonstrate that arsenic trioxide and pentamidine are essentially devoid of
      direct acute effects on cardiac repolarization or inhibition of I(HERG).

PMID- 16278314
TI  - Pharmacy teams lack FEMA support.

PMID- 16278315
TI  - Changes in IVIG marketplace challenge pharmacists.

PMID- 16278316
TI  - HIV occupational exposure guidelines revised.

PMID- 16278318
TI  - New drugs.

PMID- 16278319
TI  - Prevention of venous thromboembolism in the medically ill.

PMID- 16278320
TI  - Putting motivational interviewing in perspective.

PMID- 16278322
TI  - Unavailability of 10% alcohol in 5% dextrose injection.

PMID- 16278324
TI  - From "drug-related problems" to "negative clinical outcomes".

PMID- 16278323
TI  - Accuracy of parenteral nutrition solutions compounded with automated systems and
      by hand.

PMID- 16278326
TI  - Availability of different dosage forms of scopolamine.

PMID- 16278327
TI  - Hyperphosphatemia and phosphate binders.
AB  - PURPOSE: The pathophysiology of hyperphosphatemia associated with end-stage renal
      disease and treatment with phosphate binders are discussed. SUMMARY: Phosphorus
      is an essential element necessary for the normal function of the human body,
      required for skeletal construction and synthesis of DNA, proteins, and adenosine
      triphosphate. In healthy individuals, serum phosphorus concentrations are
      maintained between 2.5 and 4.5 mg/dL through diet and renal excretion. In renal
      insufficiency, phosphorus excretion declines and hyperphosphatemia develops. The
      body's compensation mechanisms cause secondary hyperparathyroidism and renal
      osteodystrophy. Phosphate binders provide an effective means for managing serum
      phosphate. Commercially available phosphate binders include calcium carbonate,
      calcium acetate, sevelamer, lanthanum, and, rarely, aluminum hydroxide. Because
      of aluminum's known toxicities, aluminum-based phosphate binders have a limited
      place in therapy. Calcium carbonate's benefits are seen over a narrow gastric pH
      range, thereby limiting the drug's utility. Calcium acetate is effective over a
      wide pH range. Other phosphate binders, including sevelamer hydrochloride and
      lanthanum carbonate, have recently entered the market, but their use remains
      controversial. CONCLUSION: If left untreated, hyperphosphatemia can result in
      secondary hyperparathyroidism, renal osteodystrophy, and metastatic calcification
      of blood vessels and soft tissue. The treatment of hyperphosphatemia in patients
      with chronic renal failure includes dialysis, dietary phosphorus restrictions,
      phosphate-binding medications, and vitamin D analogs. Selection of phosphate
      binders should be based on patient characteristics, including serum phosphate,
      serum calcium, and intact parathyroid hormone concentrations, and patient
      tolerability.

PMID- 16278328
TI  - Pramlintide acetate.
AB  - PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, adverse effects,
      and dosage and administration of pramlintide are reviewed. SUMMARY: Pramlintide,
      a synthetic analogue of the human hormone amylin, is the first of a new class of
      amylinomimetic compounds. It was approved in March 2005 as a subcutaneous
      injection for the adjunctive treatment of patients who have type 1 or 2 diabetes
      mellitus and have failed to achieve glycemic control despite optimal therapy with
      insulin. Pramlintide complements the effects of insulin in postprandial glucose
      regulation by decreasing glucagon secretion. Pramlintide exhibits linear
      pharmacokinetics, and peak serum levels are reached within 30 minutes of
      administration. The drug is predominantly renally eliminated, with a mean
      elimination half-life of 30-50 minutes. Clinical trials have shown that
      pramlintide suppresses postmeal glucagon secretion, slows gastric emptying,
      reduces postprandial glucose levels, and improves glycemic control while managing
      weight loss. Pramlintide has also been shown to decrease hemoglobin A(1c), serum
      fructosamine, and total cholesterol levels. Pramlintide has been associated with
      an increased risk of insulin-induced severe hypoglycemia; other adverse events
      include nausea, anorexia, fatigue, and vomiting. The dosage varies with the type
      of diabetes. Because of the cost associated with the complications of
      uncontrolled diabetes, pramlintide may have a beneficial effect on total costs
      associated with this chronic disease. CONCLUSION: Pramlintide in combination with
      insulin is a potential therapeutic option for improving glycemic control in
      patients with diabetes, but the increased risk of hypoglycemia must be
      aggressively monitored.

PMID- 16278329
TI  - Patterns of antihypertensive therapy in new users of angiotensin II-receptor
      blockers.
AB  - PURPOSE: The patterns of angiotensin II-receptor blocker (ARB) therapy in
      patients with and without a history of antihypertensive use were studied.
      METHODS: Data for this retrospective cohort study were obtained from Caremark's
      data warehouse. Patients were included in the analysis if they filled
      prescriptions for ARBs only, did not receive ARB therapy within the 6 months
      before the filling of the first ARB prescription (index date), were continuously
      eligible for benefits for 6 months before the index date, were eligible for
      prescription benefits for the 12 months following the index date, and were age 20
      80 years. RESULTS: Of the 174,573 patients sampled, 53.4% were new to all
      antihypertensive therapies. Of the patients receiving an ARB, 67.9% received
      another antihypertensive during the evaluation period. Over 40% of patients new
      to all antihypertensive therapies had no other antihypertensive added to their
      ARB regimen. Of the patients with a history of antihypertensive use, 22.3%
      discontinued all antihypertensives before starting therapy with an ARB. Patients
      starting therapy with losartan and valsartan were less likely to be treated with
      mono-therapy and more likely to be treated with ARB-diuretic therapy than were
      patients starting therapy with telmisartan, irbesartan, or candesartan.
      CONCLUSION: Patients who started antihypertensive therapy with ARBs tended to be
      new to antihypertensive therapy and, in a plurality of cases, continued to
      receive therapy with ARBs only. More than a fifth of patients who received
      antihypertensive therapy in the recent past were switched from that therapy to
      treatment with ARBs only. Treatment patterns differed by initial ARB used and the
      demographic profile of the patient.

PMID- 16278330
TI  - I.V. admixture contamination rates: traditional practice site versus a class 1000
      cleanroom.
AB  - PURPOSE: The contamination rates associated with the preparation of medium-risk
      i.v. admixtures in a traditional practice site and in a class 1000 cleanroom were
      compared. METHODS: Simulated product media fills served as the samples. Each
      investigator, a pharmacist and a pharmacy technician, prepared 500 vials and 500
      small-volume parenteral (SVP) bags in five separate runs at a traditional
      practice site and in a cleanroom. United States Pharmacopeia chapter 797 medium
      risk compounding procedures were followed, and strict adherence to aseptic
      technique was employed. Single-strength tryptic soy broth was substituted for the
      drug and diluent in the admixtures. Positive and negative controls were also
      prepared and stored for the duration of the study. The pharmacist and technician
      prepared a total of 4057 samples: 2027 samples (1014 vials and 1013 SVP bags)
      were prepared in a class 1000 cleanroom, and 2030 (1014 vials and 1016 SVP bags)
      were prepared at a traditional practice site. RESULTS: Contamination rates did
      not significantly differ between the traditional practice site (0.296%) and the
      cleanroom environment (0.344%) (p = 1.0). A significant difference in the number
      of contaminated samples was found between the two investigators (2 of 2057 were
      contaminated by the pharmacist and 11 of 2000 were contaminated by the
      technician) (p = 0.012). Contamination rates by the pharmacist (p = 1.0) and
      technician (p = 1.0) did not significantly differ between sites. CONCLUSION: The
      most important variable affecting microbial contamination of admixtures was the
      aseptic technique of personnel, not the environment in which the drugs were
      compounded.

PMID- 16278331
TI  - Computer program to assist pharmacy management of an inpatient warfarin dosing
      service.

PMID- 16278332
TI  - Using data from automated dispensing units to identify adverse drug reactions.

PMID- 16278333
TI  - Pharmacists' perceptions of the pharmaceutical industry.

PMID- 16278334
TI  - Stability of pantoprazole in 0.9% sodium chloride injection in polypropylene
      syringes.

PMID- 16278335
TI  - Bar-code verification of medication administration in a small hospital.

PMID- 16278336
TI  - Therapeutic interchange of darbepoetin alfa for epoetin alfa in a
      multiinstitution health care system.

PMID- 16278337
TI  - ASHP statement on the over-the-counter availability of statins.

PMID- 16278339
TI  - Genetic variations of tubular sodium reabsorption leading to "primary"
      hypertension: from gene polymorphism to clinical symptoms.
AB  - The definition of the most appropriate strategy to demonstrate causation of a
      given genetic-molecular mechanism in a complex multifactorial polygenic disease
      like hypertension is hampered by the underestimation of the complexity arising
      from the genetic and environmental interactions. To disentangle this complexity,
      we developed a strategy based on six steps: 1) isolation of a rodent model of
      hypertension (Milan hypertensive strain and Milan normotensive strain) that
      shares some pathophysiological abnormalities with human primary hypertension; 2)
      definition in the model of the sequence of events linking these abnormalities to
      a genetic molecular mechanism; 3) determination of the polymorphism of the three
      adducin genes discovered in the model both in rats and in humans; 4) comparison
      at biochemical and physiological levels between the rodent models and the
      hypertensive carriers of the "mutated" gene variants; 5) evaluation of the impact
      of the adducin genes in hypertension and its organ complications with association
      and linkage studies in humans, also considering the genetic and environmental
      interactions; and 6) development of a pharmacogenomic approach aimed at
      establishing the therapeutic benefit of a drug interfering with the sequence of
      events triggered by adducin and their effect's size. The bulk of data obtained
      demonstrates the importance of a multidisciplinary approach considering a variety
      of genetic and environmental interactions. Adducin functions within the cells as
      a heterodimer composed of a combination of three subunits. Each of these subunits
      is coded by genes mapping to different chromosomes. Therefore, the interaction
      among these genes, taken together with the interactions with other modulatory
      genes or with the environment, is indispensable to establish the adducin clinical
      impact. The hypothesis that adducin polymorphism favors the development of
      hypertension via an increased tubular sodium reabsorption is well supported by a
      series of consistent experimental and clinical data. Many mechanistic aspects,
      underlying the link between these genes and clinical symptoms, need to be
      clarified. The clinical effect size of adducin must be established also with the
      contribution of pharmacogenomics with a drug that selectively interferes with the
      sequence of events triggered by the mutated adducin.

PMID- 16278340
TI  - Remote preconditioning and delayed cardioprotection in skeletal muscle.

PMID- 16278341
TI  - The mysterious role of prostaglandin E2 in the medullary raphe: a hot topic or
      not?

PMID- 16278342
TI  - Reactive oxygen species production by mitochondria in endothelial cells exposed
      to reoxygenation after hypoxia and glucose depletion is mediated by ceramide.
AB  - In endothelium, reoxygenation after hypoxia (H/R) has been shown to induce
      production of reactive oxygen species (ROS) by complex III of the mitochondrial
      respiratory chain. The purpose of the present study was to test the involvement
      of ceramide in this phenomenon. Human umbilical vein endothelial cells underwent
      2 h of hypoxia (PO2, approximately 20 mmHg) without glucose and 1 h of
      reoxygenation (PO2, approximately 120 mmHg) with glucose. ROS production was
      measured by the fluorescent marker 2',7'-dichlorodihydrofluorescein diacetate,
      and cell death by propidium iodide. We showed that 1) after 1 h of reoxygenation,
      fluorescence had risen and that ROS production was inhibited by desipramine, an
      inhibitor of sphingomyelinase, an enzyme responsible for ceramide production (126
      +/- 7% vs. 48 +/- 12%, P < 0.05); 2) administration of ceramide (N
      acetylsphingosine) per se (i.e., in the absence of H/R) induced ROS production
      (65 +/- 3%), which was inhibited by complex III inhibitor: antimycin A (24 +/-
      3%, P < 0.0001), or stigmatellin (31 +/- 2%, P < 0.0001); 3)
      hypoxia/reoxygenation-induced ROS production was not affected by either ceramide
      activated protein kinase inhibitor dimethyl aminopurine or mitochondrial
      permeability transition inhibitor cyclosporin A but was significantly inhibited
      by the antiapoptotic protein Bcl-2 (82 +/- 8%, P < 0.05); 4) ceramide-induced ROS
      production was also inhibited by Bcl-2 (41 +/- 4%, P < 0.0001). These results
      demonstrate that in endothelial cells submitted to hypoxia and glucose depletion
      followed by reoxygenation with glucose, the pathway implicated in mitochondrial
      complex III ROS production is ceramide dependent and is decreased by the
      antiapoptotic protein Bcl-2.

PMID- 16278343
TI  - Organellar proteomics: analysis of pancreatic zymogen granule membranes.
AB  - The zymogen granule (ZG) is the specialized organelle in pancreatic acinar cells
      for digestive enzyme storage and regulated secretion and has been a model for
      studying secretory granule functions. In an initial effort to comprehensively
      understand the functions of this organelle, we conducted a proteomic study to
      identify proteins from highly purified ZG membranes. By combining two-dimensional
      gel electrophoresis and two-dimensional LC with tandem mass spectrometry, 101
      proteins were identified from purified ZG membranes including 28 known ZG
      proteins and 73 previously unknown proteins, including SNAP29, Rab27B, Rab11A,
      Rab6, Rap1, and myosin Vc. Moreover several hypothetical proteins were identified
      that represent potential novel proteins. The ZG localization of nine of these
      proteins was further confirmed by immunocytochemistry. To distinguish intrinsic
      membrane proteins from soluble and peripheral membrane proteins, a quantitative
      proteomic strategy was used to measure the enrichment of intrinsic membrane
      proteins through the purification process. The iTRAQ ratios correlated well with
      known or Transmembrane Hidden Markov Model-predicted soluble or membrane
      proteins. By combining subcellular fractionation with high resolution separation
      and comprehensive identification of proteins, we have begun to elucidate zymogen
      granule functions through proteomic and subsequent functional analysis of its
      membrane components.

PMID- 16278344
TI  - Videofluoroscopy and swallowing studies for neurologic disease: a primer.
AB  - Many patients with neurologic impairment due to stroke, multiple sclerosis,
      trauma, bulbar palsy, and other disorders have difficulty swallowing.
      Videofluoroscopy can provide important information on patterns of impairment of
      the swallowing mechanism, allowing important changes in patient treatment. The
      detailed videofluoroscopic evaluation required to provide this information is now
      seldom taught and is practiced by relatively few radiologists. The aim of this
      article is to (a) describe the indications for videofluoroscopic swallowing
      studies in the evaluation of patients with neurologic conditions affecting
      swallowing, (b) describe the techniques for evaluating the swallow mechanism with
      videofluoroscopy in a standardized manner, and (c) use cine videofluoroscopy to
      illustrate the range of abnormalities that can be demonstrated for some of these
      conditions and discuss the effect of patient treatment.

PMID- 16278347
TI  - The cover. A surgeon and a line of patients.

PMID- 16278346
TI  - Distinct and cooperative functions of phytochromes A, B, and C in the control of
      deetiolation and flowering in rice.
AB  - We have isolated phytochrome B (phyB) and phyC mutants from rice (Oryza sativa)
      and have produced all combinations of double mutants. Seedlings of phyB and phyB
      phyC mutants exhibited a partial loss of sensitivity to continuous red light (Rc)
      but still showed significant deetiolation responses. The responses to Rc were
      completely canceled in phyA phyB double mutants. These results indicate that phyA
      and phyB act in a highly redundant manner to control deetiolation under Rc. Under
      continuous far-red light (FRc), phyA mutants showed partially impaired
      deetiolation, and phyA phyC double mutants showed no significant residual
      phytochrome responses, indicating that not only phyA but also phyC is involved in
      the photoperception of FRc in rice. Interestingly, the phyB phyC double mutant
      displayed clear R/FR reversibility in the pulse irradiation experiments,
      indicating that both phyA and phyB can mediate the low-fluence response for gene
      expression. Rice is a short-day plant, and we found that mutation in either phyB
      or phyC caused moderate early flowering under the long-day photoperiod, while
      monogenic phyA mutation had little effect on the flowering time. The phyA
      mutation, however, in combination with phyB or phyC mutation caused dramatic
      early flowering.

PMID- 16278345
TI  - Interactions between the cell cycle and embryonic patterning in Arabidopsis
      uncovered by a mutation in DNA polymerase epsilon.
AB  - Pattern formation and morphogenesis require coordination of cell division rates
      and orientations with developmental signals that specify cell fate. A viable
      mutation in the TILTED1 locus, which encodes the catalytic subunit of DNA
      polymerase epsilon of Arabidopsis thaliana, causes a lengthening of the cell
      cycle by approximately 35% throughout embryo development and alters cell type
      patterning of the hypophyseal lineage in the root, leading to a displacement of
      the root pole from its normal position on top of the suspensor. Treatment of
      preglobular and early globular stages, but not later stage, embryos with the DNA
      polymerase inhibitor aphidicolin leads to a similar phenotype. The results
      uncover an interaction between the cell cycle and the processes that determine
      cell fate during plant embryogenesis.

PMID- 16278348
TI  - Biomedical journals probe peer review.

PMID- 16278349
TI  - Nobels honor research on ulcer microbe, "green" drug production method.

PMID- 16278350
TI  - Internet seen as clinical research tool.

PMID- 16278351
TI  - Bats may be SARS reservoir.

PMID- 16278352
TI  - Prone positioning in children with acute lung injury.

PMID- 16278353
TI  - Coronary angiography with multislice computed tomography.

PMID- 16278354
TI  - Neonatal signs after in utero exposure to selective serotonin reuptake
      inhibitors.

PMID- 16278355
TI  - Coffee consumption and development of type 2 diabetes.

PMID- 16278356
TI  - Neonatal signs after in utero exposure to selective serotonin reuptake
      inhibitors.

PMID- 16278357
TI  - Possible child-to-mother transmission of HIV by breastfeeding.

PMID- 16278358
TI  - Clinical decision support and appropriateness of antimicrobial prescribing: a
      randomized trial.
AB  - CONTEXT: The impact of clinical decision support systems (CDSS) on antimicrobial
      prescribing in ambulatory settings has not previously been evaluated. OBJECTIVE:
      To measure the added value of CDSS when coupled with a community intervention to
      reduce inappropriate prescribing of antimicrobial drugs for acute respiratory
      tract infections. DESIGN, PARTICIPANTS AND SETTING: Cluster randomized trial that
      included 407,460 inhabitants and 334 primary care clinicians in 12 rural
      communities in Utah and Idaho (6 with 1 shared characteristic and 6 with
      another), and a third group of 6 communities that served as nonstudy controls.
      The preintervention period was January to December 2001 and the postintervention
      period was January 2002 to September 2003. Acute respiratory tract infection
      diagnoses were classified into groups based on indication for antimicrobial use.
      Multilevel regression methods were applied to account for the clustered design.
      INTERVENTION: Six communities received a community intervention alone and 6
      communities received community intervention plus CDSS that were targeted toward
      primary care clinicians. The CDSS comprised decision support tools on paper and a
      handheld computer to guide diagnosis and management of acute respiratory tract
      infection. MAIN OUTCOME MEASURE: Community-wide antimicrobial usage was assessed
      using retail pharmacy data. Diagnosis-specific antimicrobial use was compared by
      chart review. RESULTS: Within CDSS communities, 71% of primary care clinicians
      participated in the use of CDSS. The prescribing rate decreased from 84.1 to 75.3
      per 100 person-years in the CDSS arm vs 84.3 to 85.2 in community intervention
      alone, and remained stable in the other communities (P = .03). A total of 13,081
      acute respiratory tract infection visits were abstracted. The relative decrease
      in antimicrobial prescribing for visits in the antibiotics "never-indicated"
      category during the post-intervention period was 32% in CDSS communities and 5%
      in community intervention-alone communities (P = .03). Use of macrolides
      decreased significantly in CDSS communities but not in community intervention
      alone communities. CONCLUSION: CDSS implemented in rural primary care settings
      reduced overall antimicrobial use and improved appropriateness of antimicrobial
      selection for acute respiratory tract infections. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT00235703.

PMID- 16278359
TI  - Antibiotic treatment of children with sore throat.
AB  - CONTEXT: Of children with sore throat, 15% to 36% have pharyngitis caused by
      group A beta-hemolytic streptococci (GABHS). Performance of a GABHS test prior to
      antibiotic prescribing is recommended for children with sore throat. Penicillin,
      amoxicillin, erythromycin, and first-generation cephalosporins are the
      recommended antibiotics for treatment of sore throat due to GABHS. OBJECTIVES: To
      measure rates of antibiotic prescribing and GABHS testing and to evaluate the
      association between testing and antibiotic treatment for children with sore
      throat. DESIGN, SETTING, AND PARTICIPANTS: Analysis of visits by children aged 3
      to 17 years with sore throat to office-based physicians, hospital outpatient
      departments, and emergency departments in the National Ambulatory Medical Care
      Survey and National Hospital Ambulatory Medical Care Survey, 1995 to 2003 (N =
      4158) and of a subset of visits with GABHS testing data (n = 2797). MAIN OUTCOME
      MEASURES: National rates of antibiotic prescribing, prescribing of antibiotics
      recommended and not recommended for GABHS, and GABHS testing. RESULTS: Physicians
      prescribed antibiotics in 53% (95% confidence interval [CI], 49%-56%) of an
      estimated 7.3 million annual visits for sore throat and nonrecommended
      antibiotics to 27% (95% CI, 24%-31%) of children who received an antibiotic.
      Antibiotic prescribing decreased from 66% of visits in 1995 to 54% of visits in
      2003 (P = .01 for trend). This decrease was attributable to a decrease in the
      prescribing of recommended antibiotics (49% to 38%; P = .002). Physicians
      performed a GABHS test in 53% (95% CI, 48%-57%) of visits and in 51% (95% CI, 45%
      57%) of visits at which an antibiotic was prescribed. GABHS testing was not
      associated with a lower antibiotic prescribing rate overall (48% tested vs 51%
      not tested; P = .40), but testing was associated with a lower antibiotic
      prescribing rate for children with diagnosis codes for pharyngitis, tonsillitis,
      and streptococcal sore throat (57% tested vs 73% not tested; P<.001).
      CONCLUSIONS: Physicians prescribed antibiotics to 53% of children with sore
      throat, in excess of the maximum expected prevalence of GABHS. Although there was
      a decrease in the proportion of children receiving antibiotics between 1995 and
      2003, this was due to decreased prescribing of agents recommended for GABHS.
      Although GABHS testing was associated with a lower rate of antibiotic prescribing
      for children with diagnosis codes of pharyngitis, tonsillitis, and streptococcal
      sore throat, GABHS testing was underused.

PMID- 16278360
TI  - Left atrial radiofrequency ablation during mitral valve surgery for continuous
      atrial fibrillation: a randomized controlled trial.
AB  - CONTEXT: Although left atrial radiofrequency ablation (RFA) is increasingly used
      for the treatment of chronic atrial fibrillation during mitral valve surgery, its
      efficacy to restore sinus rhythm and any resulting benefits have not been
      examined in the context of an adequately powered randomized trial. OBJECTIVE: To
      determine whether intraoperative RFA of the left atrium increases the long-term
      restoration of sinus rhythm and improves exercise capacity. DESIGN, SETTING, AND
      PATIENTS: Randomized, double-blind trial performed in a single UK tertiary
      referral center with enrollment between December 2001 and November 2003. A total
      of 101 patients referred for mitral valve surgery with at least 6 months' history
      of uninterrupted atrial fibrillation were assessed for eligibility; 97 were
      enrolled. Patients were followed up for 12 months. INTERVENTION: Patients were
      randomly assigned to undergo mitral valve surgery and RFA of the left atrium (n =
      49) or mitral valve surgery alone (controls; n = 48). MAIN OUTCOME MEASURES: The
      primary outcome measure was presence of sinus rhythm at 12 months; secondary
      measures were patient functional status and exercise capacity (assessed by
      shuttle-walk test), left atrial contractility, and left atrial and left
      ventricular dimension and function and plasma levels of B-type natriuretic
      peptide. RESULTS: At 12 months, sinus rhythm was present in 20 (44.4%) of 45 RFA
      patients and in 2 (4.5%) of 44 controls (rate ratio, 9.8; 95% CI, 2.4-86.3;
      P<.001). Restoration of sinus rhythm in the RFA group was accompanied by a
      greater improvement in mean (SD) shuttle-walk distance compared with controls
      (+94 [102] m vs +48 [82] m; P = .003) and a greater reduction in the plasma level
      of B-type natriuretic peptide (-104 [87] fmol/mL vs -51 [82] fmol/mL; P = .03).
      Patients randomized to receive RFA had similar rates of postoperative
      complications and deaths as control patients. CONCLUSIONS: Radiofrequency
      ablation of the left atrium during mitral valve surgery for continuous atrial
      fibrillation significantly increases the rate of sinus rhythm restoration 1 year
      postoperatively, improving patient exercise capacity. On the basis of its
      efficacy and safety, routine use of RFA of the left atrium during mitral valve
      surgery may be justified. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT00238706.

PMID- 16278361
TI  - Habitual caffeine intake and the risk of hypertension in women.
AB  - CONTEXT: Caffeine acutely increases blood pressure, but the association between
      habitual consumption of caffeinated beverages and incident hypertension is
      uncertain. OBJECTIVE: To examine the association between caffeine intake and
      incident hypertension in women. DESIGN, SETTING, AND PARTICIPANTS: Prospective
      cohort study conducted in the Nurses' Health Studies (NHSs) I and II of 155,594
      US women free from physician-diagnosed hypertension followed up over 12 years
      (1990-1991 to 2002-2003 questionnaires). Caffeine intake and possible confounders
      were ascertained from regularly administered questionnaires. We also tested the
      associations with types of caffeinated beverages. MAIN OUTCOME MEASURE: Incident
      physician-diagnosed hypertension. RESULTS: During follow-up, 19,541 incident
      cases of physician-diagnosed hypertension were reported in NHS I and 13,536 in
      NHS II. In both cohorts, no linear association between caffeine consumption and
      risk of incident hypertension was observed after multivariate adjustment (NHS I,
      P for trend = .29; NHS II, P for trend = .53). Using categorical analysis, an
      inverse U-shaped association between caffeine consumption and incident
      hypertension was found. Compared with participants in the lowest quintile of
      caffeine consumption, those in the third quintile had a 13% and 12% increased
      risk of hypertension, respectively (95% confidence interval in NHS I, 8%-18%; in
      NHS II, 6%-18%). When studying individual classes of caffeinated beverages,
      habitual coffee consumption was not associated with increased risk of
      hypertension. By contrast, consumption of cola beverages was associated with an
      increased risk of hypertension, independent of whether it was sugared or diet
      cola (P for trend <.001). CONCLUSION: No linear association between caffeine
      consumption and incident hypertension was found. Even though habitual coffee
      consumption was not associated with an increased risk of hypertension,
      consumption of sugared or diet cola was associated with it. Further research to
      elucidate the role of cola beverages in hypertension is warranted.

PMID- 16278362
TI  - Relationship between serum parathyroid hormone levels, vitamin D sufficiency, and
      calcium intake.
AB  - CONTEXT: Adequate vitamin D status for optimum bone health has received increased
      recognition in recent years; however, the ideal intake is not known. Serum 25
      hydroxyvitamin D is the generally accepted indicator of vitamin D status, but no
      universal reference level has been reached. OBJECTIVE: To investigate the
      relative importance of high calcium intake and serum 25-hydroxyvitamin D for
      calcium homeostasis, as determined by serum intact parathyroid hormone (PTH).
      DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 2310 healthy
      Icelandic adults who were divided equally into 3 age groups (30-45 years, 50-65
      years, or 70-85 years) and recruited from February 2001 to January 2003. They
      were administered a semi-quantitative food frequency questionnaire, which
      assessed vitamin D and calcium intake. Participants were further divided into
      groups according to calcium intake (<800 mg/d, 800-1200 mg/d, and >1200 mg/d) and
      serum 25-hydroxyvitamin D level (<10 ng/mL, 10-18 ng/mL, and >18 ng/mL). MAIN
      OUTCOME MEASURE: Serum intact PTH as determined by calcium intake and vitamin D.
      RESULTS: A total of 944 healthy participants completed all parts of the study.
      After adjusting for relevant factors, serum PTH was lowest in the group with a
      serum 25-hydroxyvitamin D level of more than 18 ng/mL but highest in the group
      with a serum 25-hydroxyvitamin D level of less than 10 ng/mL. At the low serum 25
      hydroxyvitamin D level (<10 ng/mL), calcium intake of less than 800 mg/d vs more
      than 1200 mg/d was significantly associated with higher serum PTH (P = .04); and
      at a calcium intake of more than 1200 mg/d, there was a significant difference
      between the lowest and highest vitamin D groups (P = .04). CONCLUSIONS: As long
      as vitamin D status is ensured, calcium intake levels of more than 800 mg/d may
      be unnecessary for maintaining calcium metabolism. Vitamin D supplements are
      necessary for adequate vitamin D status in northern climates.

PMID- 16278363
TI  - Ricin poisoning: a comprehensive review.
AB  - CONTEXT: The recent discoveries of ricin, a deadly biologic toxin, at a South
      Carolina postal facility, a White House mail facility, and a US senator's office
      has raised concerns among public health officials, physicians, and citizens.
      Ricin is one of the most potent and lethal substances known, particularly when
      inhaled. The ease with which the native plant (Ricinus communis) can be obtained
      and the toxin extracted makes ricin an attractive weapon. OBJECTIVES: To
      summarize the literature on ricin poisoning and provide recommendations based on
      our best professional judgment for clinicians and public health officials that
      are faced with deliberate release of ricin into the environment. LITERATURE
      ACQUISITION: Using PubMed, we searched MEDLINE and OLDMEDLINE databases (January
      1950-August 2005). The Chemical and Biological Information Analysis Center
      database was searched for historical and military literature related to ricin
      toxicity. Book chapters, unpublished reports, monographs, relevant news reports,
      and Web material were also reviewed to find nonindexed articles. RESULTS: Most
      literature on ricin poisoning involves castor bean ingestion and experimental
      animal research. Aerosol release of ricin into the environment or adulteration of
      food and beverages are pathways to exposure likely to be exploited. Symptoms
      after ingestion (onset within 12 hours) are nonspecific and may include nausea,
      vomiting, diarrhea, and abdominal pain and may progress to hypotension, liver
      failure, renal dysfunction, and death due to multiorgan failure or cardiovascular
      collapse. Inhalation (onset of symptoms is likely within 8 hours) of ricin is
      expected to produce cough, dyspnea, arthralgias, and fever and may progress to
      respiratory distress and death, with few other organ system manifestations.
      Biological analytic methods for detecting ricin exposure are undergoing
      investigation and may soon be available through reference laboratories. Testing
      of environmental samples is available through federal reference laboratories.
      Currently, no antidote, vaccine, or other specific effective therapy is available
      for ricin poisoning or prevention. Prompt treatment with supportive care is
      necessary to limit morbidity and mortality. CONCLUSION: Health care workers and
      public health officials should consider ricin poisoning in patients with
      gastrointestinal or respiratory tract illness in the setting a credible threat.
      Poison control centers and public health authorities should be notified of any
      known illness associated with ricin exposure.

PMID- 16278364
TI  - Appropriate use of antimicrobial drugs: a better prescription is needed.

PMID- 16278365
TI  - Making sense of the maze: which patients with atrial fibrillation will benefit?

PMID- 16278366
TI  - JAMA patient page. Vitamin D.

PMID- 16278367
TI  - Sildenafil improves sleep-related erections in hypogonadal men: evidence from a
      randomized, placebo-controlled, crossover study of a synergic role for both
      testosterone and sildenafil on penile erections.
AB  - To study the effects of sildenafil on human sleep-related erections according to
      the state of androgenization, we evaluated the effects of sildenafil on sleep
      related erections in hypogonadal men before and during testosterone replacement
      treatment and in control subjects. We enrolled 24 hypogonadal men and 24 healthy
      men as a control group. All hypogonadal subjects had very low testosterone levels
      (<200 ng/dL [6.9 nmol/L]) [corrected] All subjects underwent nocturnal penile
      tumescence and rigidity monitoring (NPTRM) for 3 consecutive nights and were
      randomly assigned to consume either 50 mg of sildenafil or placebo 1 hour before
      bedtime on the second or third night of nocturnal penile monitoring. The
      hypogonadal subjects were tested twice, first without replacement treatment (H-T)
      and then after at least 6 months of testosterone replacement therapy (H+T). The
      subjects of the control group (C) were tested once. The following parameters of
      sleep-related erections were analyzed: total number of valid erections, total
      duration of both rigidity greater than or equal 70% and increase in penile
      circumference greater than or equal 30 mm, maximum rigidity, and maximum increase
      in penile circumference. NPTRM parameters were reduced in hypogonadal men before
      testosterone treatment (H-T+P) when compared with control subjects taking placebo
      (C+P). NPTRM parameters after testosterone (H+T+P) and sildenafil (H-T+S)
      administration were similar to that of control subjects taking placebo (C+P).
      When the statistical analysis was restricted to the hypogonadal men before
      testosterone treatment, sildenafil alone significantly increased NPTRM parameters
      when compared with placebo (H-T+S vs H-T+P). Testosterone restored normal
      erections when administered to hypogonadal subjects (H+T+P vs H-T+P); in
      hypogonadal men, however, the combined treatment (sildenafil plus testosterone)
      resulted in the maximum positive effect on NPTRM parameters. When the increase
      from baseline was analyzed, the effects of testosterone plus sildenafil were
      greater than the sum of the effects of each drug used alone. In conclusion,
      sildenafil administered at bedtime improves sleep-related erections in
      hypogonadal men, suggesting that the nitric oxide pathway may be
      pharmacologically enrolled and enhanced despite low serum testosterone.
      Furthermore, these data strongly support the idea of a synergic effect on sleep
      related erections of sildenafil and testosterone.

PMID- 16278368
TI  - Sonic hedgehog pathway inhibition alters epididymal function as assessed by the
      development of sperm motility.
AB  - The sonic hedgehog (Shh) signaling pathway plays a role in pattern orientation in
      the developing embryo and has been shown to be required for development of the
      prostate and external genitalia. Recent evidence has shown that important
      elements of the Shh pathway are also expressed in the adult mouse epididymis at
      both the gene and protein levels. The objective of the present investigation was
      to refine the expression pattern of Shh in the mouse epididymis and to determine
      if the Shh pathway is important for epididymal function vis-a-vis sperm
      maturation. The former was achieved by microarray analysis of Shh expression in
      all segments of the mouse epididymis, and the latter was determined by 14-day
      administration of cyclopamine, a Shh pathway inhibitor, followed by a microassay
      for the activation and duration of cauda epididymal sperm motility. Shh pathway
      inhibition was monitored by semiquantitative reverse transcriptase-polymerase
      chain reaction for expression of epididymal Gli1 and Gli3. The Gli family of
      transcription factors is commonly activated and regulated by Shh pathway
      activation. Cyclopamine treatment reduced Gli1 expression by 61% and initiation
      of cauda sperm motility by 50%. Gli3 expression was reduced by approximately 50%.
      Subsequent cluster analysis using the microarray data on epididymal gene
      expression highlighted several potential target genes for the Shh pathway, the
      most prominent of which is prostaglandin D2 synthase. These results indicate that
      an operating Shh pathway is important in the murine epididymis for the
      development of sperm motility and implies a role for Shh signaling in adult
      epididymal function.

PMID- 16278369
TI  - Polyol pathway in human epididymis and semen.
AB  - Two enzymes are involved in the polyol pathway: an aldose reductase that reduces
      glucose in sorbitol followed by its oxidation in fructose by sorbitol
      dehydrogenase. It has been previously shown that both enzymes are presented in
      the bovine epididymis, where they are associated with membranous vesicles called
      epididymosomes. Based on the distribution of these enzymes, it has been
      hypothesized that the polyol pathway can modulate sperm motility during the
      epididymal transit. In the present study, polyol pathway was investigated in
      semen and along the epididymis in humans in order to determine if sperm
      maturation can be associated with this sugar pathway. Western blot analysis shows
      that both aldose reductase and sorbitol dehydrogenase are associated with
      ejaculated spermatozoa and prostasomes in humans. These enzymes are also
      associated with epididymosomes collected during surgical vasectomy reversal.
      Western blot, Northern blot, and reverse transcription-polymerase chain reaction
      analysis show that aldose reductase and sorbitol dehydrogenase are expressed at
      the transcriptional and translational levels along the human epididymis. Unlike
      what occurs in the bovine model, distribution of these enzymes is rather uniform
      along the human excurrent duct. Immunohistological studies together with Western
      blot analysis performed on epididymosomes preparations indicate that the polyol
      pathway enzymes are secreted by the epididymal epithelium. These results indicate
      that the polyol pathway plays a role in human sperm physiology.

PMID- 16278370
TI  - Effects of chemotherapeutic agents for testicular cancer on the male rat
      reproductive system, spermatozoa, and fertility.
AB  - Testicular cancer is the most common cancer affecting men of reproductive age.
      Advances in treatment of the disease, which include the coadministration of
      bleomycin, etoposide, and cis-platinum (BEP), have brought the cure rate to over
      90%. This high cure rate, coupled with the young age of patients, makes
      elucidation of the impact of the treatment on reproductive function, fertility,
      and progeny outcome increasingly important. The goal of this study was to
      determine the effects of BEP, in doses analogous to those given to humans, on the
      male reproductive system, spermatozoa, fertility, and progeny outcome in an
      animal model. Male Sprague-Dawley rats were treated daily with BEP for 3 cycles
      of 3 weeks each, for a total of 9 weeks. After 6 and 9 weeks, males were mated to
      2 groups of untreated females. BEP treatment resulted in decreases in testicular
      and epididymal weights of 52% and 28%, respectively, when compared to control.
      Decreased testis and epididymis weights were accompanied by impairment of
      spermatogenesis and by a decrease in spermatozoal count of nearly 90% (11.9 x
      10(7) spermatozoa per caput epididymidis in control vs 1.65 x 10(7) in BEP
      treated rats). The percent of motile spermatozoa in the treated rats was more
      than 30% lower than in controls. Defects in the flagella of spermatozoa increased
      by more than twofold in the midpiece, and by more than sixfold in the principal
      piece. Paternal BEP treatment, for either 6 or 9 weeks, did not affect fertility,
      pre- or postimplantation loss, litter size, or sex ratio among progeny on
      gestation day 21. In contrast, among the pregnancies allowed to proceed to
      delivery, a significant number of pups sired by males treated with BEP for 9
      weeks died between birth and postnatal day 2; this was not observed in pups sired
      by males treated for 6 weeks. Markers of postnatal development were not affected
      in the surviving offspring from either group. Thus, despite the dramatic effects
      of the testicular cancer drug regimen on spermatogenesis, the numbers of
      spermatozoa, and their motility and morphology, male rats were fertile. While
      fetal development was apparently normal, early postnatal mortality, which may be
      associated with a delay in parturition, was elevated among the progeny sired by
      males exposed to BEP for 9 weeks.

PMID- 16278371
TI  - Identification of proteins in the accessory sex gland fluid associated with
      fertility indexes of dairy bulls: a proteomic approach.
AB  - We evaluated the expression of proteins in the accessory sex gland fluid (AGF)
      and their relationships with fertility indexes of dairy bulls. Fertility was
      normalized as the percentage point deviation of their nonreturn rates (PD) from
      the average fertility of all bulls from a given artificial insemination center.
      Services associated with each sire ranged from 269 to 77 321 and PD values from
      +7.7% to -18.1%. AGF, from 37 bulls, was obtained with an artificial vagina after
      cannulation of the vasa deferentia. Proteins from AGF were separated by 2
      dimensional SDS-PAGE followed by staining with Coomassie blue and analysis of
      polypeptide maps using PDQuest software. Bulls were divided in groups based on PD
      values and the optical density of spots in the AGF gels used as independent
      variables to predict bull fertility. Proteins were identified by capillary liquid
      chromatography nanoelectrospray ionization tandem mass spectrometry (CapLC
      MS/MS). An average of 52 +/- 5 spots was detected in the AGF gels, but there were
      no spots unique to groups of either high- (PD > or = 0) or low- (PD < 0)
      fertility sires. The former were neither less nor more homogeneous than the
      latter based on correlations of all matched spots between pairs of AGF maps.
      However, high fertility of dairy bulls was significantly associated with lower
      expression of 14-kDa spermadhesin Z13 isoforms and higher amounts of 55-kDa
      osteopontin and 58-kDa phospholipase A2 (PLA2) isoforms. The average intensity of
      5 spots identified as BSP 30 kDa in the AGF gels had a quadratic association with
      fertility indexes (R2 = .18; P = .03). PD values of bulls were related (R2 = .56)
      to the quantity of spermadhesin, osteopontin, and BSP 30 kDa in the AGF
      polypeptide maps. Bull fertility was also determined by another equation (R2 =
      .53) with spermadhesin, BSP 30 kDa, and PLA2 as independent variables. We
      conclude that interactions among several proteins in accessory sex gland fluid
      explain a significant proportion of the variation in fertility scores of mature
      dairy sires.

PMID- 16278372
TI  - Deficiency of glutathione transferase zeta causes oxidative stress and activation
      of antioxidant response pathways.
AB  - Glutathione S-transferase (GST) zeta (GSTZ1-1) plays a significant role in the
      catabolism of phenylalanine and tyrosine, and a deficiency of GSTZ1-1 results in
      the accumulation of maleylacetoacetate and its derivatives maleylacetone (MA) and
      succinylacetone. Induction of GST subunits was detected in the liver of Gstz1(-/
      ) mice by Western blotting with specific antisera and high-performance liquid
      chromatography analysis of glutathione affinity column-purified proteins. The
      greatest induction was observed in members of the mu class. Induction of
      NAD(P)H:quinone oxidoreductase 1 and the catalytic and modifier subunits of
      glutamate-cysteine ligase was also observed. Many of the enzymes that are induced
      in Gstz1(-/-) mice are regulated by antioxidant response elements that respond to
      oxidative stress via the Keap1/Nrf2 pathway. It is significant that diminished
      glutathione concentrations were also observed in the liver of Gstz1(-/-) mice,
      which supports the conclusion that under normal dietary conditions, the
      accumulation of electrophilic intermediates such as maleylacetoacetate and MA
      results in a high level of oxidative stress. Elevated GST activities in the
      livers of Gstz1(-/-) mice suggest that GSTZ1-1 deficiency may alter the
      metabolism of some drugs and xenobiotics. Gstz1(-/-) mice given acetaminophen
      demonstrated increased hepatotoxicity compared with wild-type mice. This toxicity
      may be attributed to the increased GST activity or the decreased hepatic
      concentrations of glutathione, or both. Patients with acquired deficiency of
      GSTZ1-1 caused by therapeutic exposure to dichloroacetic acid for the clinical
      treatment of lactic acidosis may be at increased risk of drug- and chemical
      induced toxicity.

PMID- 16278374
TI  - Chemokine receptor 7, a new player in regulating apoptosis of CD8+ T cells in
      cancer patients.

PMID- 16278373
TI  - Rapid modulation of P-glycoprotein-mediated transport at the blood-brain barrier
      by tumor necrosis factor-alpha and lipopolysaccharide.
AB  - At the blood-brain barrier, P-glycoprotein, an ATP-driven drug efflux pump,
      selectively limits drug access to the brain parenchyma, impeding pharmacotherapy
      of a number of central nervous system (CNS) disorders. We previously used
      confocal imaging to demonstrate in isolated rat brain capillaries that endothelin
      1 (ET-1), acting through an ET(B) receptor, NO synthase, and protein kinase C,
      rapidly and reversibly reduces P-glycoprotein transport function. In this study,
      we define a link between the brain's innate immune response and functional
      regulation of P-glycoprotein. We show that exposing brain capillaries to the
      inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), activated a TNF-R1
      receptor, released ET-1, activated ET(B) receptor signaling, and essentially
      abolished P-glycoprotein-mediated transport. Bacterial lipopolysaccharide, a
      potent activator of the brain's innate immune response, reduced P-glycoprotein
      activity through TNF-alpha release, ET-1 release, and ET(B) receptor signaling.
      TNF-alpha and LPS effects had a rapid onset (minutes), were reversible, and did
      not involve changes in tight junctional permeability. These findings define a
      signaling pathway through which P-glycoprotein activity is acutely modulated.
      They show that this key component of the selective/active blood-brain barrier is
      an early target of cytokine signaling during the innate immune response and
      suggest ways to manipulate the barrier for improved CNS pharmacotherapy.

PMID- 16278375
TI  - A dynamic de-escalating dosing strategy to determine the optimal biological dose
      for antiangiogenic drugs.

PMID- 16278376
TI  - Multidrug resistance proteins in gastrointestinal stromal tumors: site-dependent
      expression and initial response to imatinib.
AB  - Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumors
      of the digestive tract and respond poorly to chemotherapy. A tyrosine kinase
      inhibitor treatment, imatinib mesylate, was recently shown to have antitumor
      effects in metastatic patients. However, this drug is a substrate for multidrug
      resistance (MDR) proteins. Therefore, we investigated the expression of ABCB1 (P
      glycoprotein), ABCC1 (MRP1), and ABCG2 (BCRP) by Western blotting in 21 GISTs and
      3 leiomyosarcomas. All the GISTs were positive for either ABCB1 (86% of cases) or
      ABCC1 expression (62%), but negative for ABCG2. ABCB1 was expressed in all
      gastric GISTs, but in only 67% of nongastric GISTs. By contrast, ABCC1 expression
      was more common in nongastric tumors (78% versus 42%). The levels of these MDR
      proteins in gastric GISTs were higher for ABCB1 (P = 0.007) and lower for ABCC1
      (P = 0.004) compared with nongastric GISTs. We found no correlation between MDR
      protein expression and the risk assessment. None of the six patients treated with
      imatinib was resistant, although all were positive for at least one MDR protein.
      These results confirm that gastric and nongastric GISTs have different biological
      characteristics and suggest that MDR proteins do not impair the initial response
      of the tumor to imatinib.

PMID- 16278377
TI  - The phenotypic plasticity of myeloma plasma cells as expressed by
      dedifferentiation into an immature, resilient, and apoptosis-resistant phenotype.
AB  - PURPOSE: We previously showed the ability of osteoclasts to support myeloma
      plasma cell survival and proliferation in vivo and ex vivo. The aim of the
      current study was to investigate osteoclast-induced phenotypic changes associated
      with long-term survival of myeloma cells in coculture. EXPERIMENTAL DESIGN: CD138
      selected myeloma plasma cells from 16 patients were cocultured with human
      osteoclasts for up to 20 weeks. RESULTS: Precultured cells were typically
      CD45(low/intermediate) CD38(high) CD138(high), CD19(-)CD34(-). After >6 weeks,
      the phenotype of cocultured myeloma cells consistently shifted to cells
      expressing CD45(intermediate/high) CD19(low) CD34(low). Expression of CD38 and
      CD138 were reduced to subpopulations with CD38(intermediate) and CD138(low)
      levels. Morphologically, cocultured plasma cells became plasmablastic. Blocking
      interleukin-6 activity did not affect the immature phenotype of myeloma cells.
      The effect of dexamethasone on myeloma cells cultured alone or in cocultures at
      baseline and after 6 weeks of coculture was determined. When baseline myeloma
      cells were cultured alone, dexamethasone significantly increased the percentage
      of apoptotic cells over the spontaneous rate. Conversely, myeloma cells recovered
      from cocultures had high survival rates and were resistant to dexamethasone
      induced apoptosis. Long-term coculture of normal CD34-expressing hematopoietic
      stem cells (HSC) resulted in loss of CD34 expression, suggesting a common
      mechanism for osteoclast-induced myeloma and HSC plasticity. CONCLUSIONS: This
      study indicates that myeloma cells have plasticity expressed by their ability to
      reprogram, dedifferentiate, and acquire autonomous survival properties.

PMID- 16278378
TI  - Signal pathway of hypoxia-inducible factor-1alpha phosphorylation and its
      interaction with von Hippel-Lindau tumor suppressor protein during ischemia in
      MiaPaCa-2 pancreatic cancer cells.
AB  - PURPOSE AND EXPERIMENTAL DESIGN: Previously, we observed that the activation of
      p38 mitogen-activated protein kinase (MAPK) and c-Jun NH(2)-terminal kinase
      (JNK1) is mediated through the activation of apoptosis signal-regulating kinase 1
      (ASK1) as a result of the reactive oxygen species-mediated dissociation of
      glutaredoxin and thioredoxin from ASK1. In this study, we examined whether p38
      MAPK and JNK1 are involved in the accumulation of hypoxia-inducible factor-1alpha
      (HIF-1alpha) during ischemia. Human pancreatic cancer MiaPaCa-2 cells were
      exposed to low glucose (0.1 mmol/L) with hypoxia (0.1% O(2)). RESULTS AND
      CONCLUSIONS: During ischemia, p38 MAPK and JNK1 were activated in MiaPaCa-2
      pancreatic cancer cells. The activated p38 MAPK, but not JNK1, phosphorylated HIF
      1alpha. Data from in vivo binding assay of von Hippel-Lindau tumor suppressor
      protein with HIF-1alpha suggests that the p38-mediated phosphorylation of HIF
      1alpha contributed to the inhibition of HIF-1alpha and von Hippel-Lindau tumor
      suppressor protein interaction during ischemia. SB203580, a specific inhibitor of
      p38 MAPK, inhibited HIF-1alpha accumulation during ischemia, probably resulting
      from the ubiquitination and degradation of HIF-1alpha.

PMID- 16278379
TI  - Relation of erythropoietin and erythropoietin receptor expression to hypoxia and
      anemia in head and neck squamous cell carcinoma.
AB  - PURPOSE: The use of erythropoietin in head and neck squamous cell carcinoma
      (HNSCC) has been associated with poor survival. This study examines the protein
      and mRNA expression of erythropoietin and erythropoietin receptor in HNSCC and
      their relation to hypoxia, hemoglobin (Hb), and clinical outcome. EXPERIMENTAL
      DESIGN: The immunohistochemical expression of erythropoietin and erythropoietin
      receptor was assessed in 151 cases of HNSCC. Expression was compared with the
      hypoxia-dependent proteins hypoxia-inducible factor-1alpha (HIF-1alpha) and
      carbonic anhydrase-9 (CA-9) and correlated with clinical outcome. The mRNA
      expression of erythropoietin and erythropoietin receptor was measured in paired
      samples of HNSCC. RESULTS: Erythropoietin and erythropoietin receptor were
      expressed in 95% and 99% of tumors, respectively. Using a weighed expression
      score, there was a positive correlation between erythropoietin and erythropoietin
      receptor expression (r = 0.18, P = 0.03). HIF-1alpha (r = 0.38, P < 0.01) and CA
      9 (r = 0.26, P = 0.002) correlated with erythropoietin expression, but there was
      no correlation with erythropoietin receptor. No correlation was found between Hb
      and erythropoietin (r = 0.07, P = 0.36) or erythropoietin receptor (r = -0.02, P
      = 0.8), and no survival difference between high and low erythropoietin or
      erythropoietin receptor expression (P = 0.59 and P = 0.98, respectively). The
      mRNA expression of erythropoietin (P = 0.03) but not erythropoietin receptor (P =
      0.62) was significantly increased in 11 paired samples of HNSCC. CONCLUSION: In
      vivo, the HIF pathway regulates erythropoietin at the mRNA level but not
      erythropoietin receptor expression in HNSCC. Anemia does not seem to influence
      the hypoxic microenvironment of tumors sufficiently to alter the expression of
      erythropoietin. The effects of exogenous erythropoietin may be acting via
      receptors expressed on tumor cells in vivo, or on vascular cells, which also
      express the pathway.

PMID- 16278380
TI  - X-Linked inhibitor of apoptosis protein expression level in colorectal cancer is
      regulated by hepatocyte growth factor/C-met pathway via Akt signaling.
AB  - PURPOSE: The inhibitor of the apoptosis protein (IAP) family members, such as the
      X-linked IAP (XIAP), survivin, and livin, are essential for cell survival and
      antiapoptosis in colorectal cancer cells. We hypothesized that the hepatocyte
      growth factor (HGF) activation in colorectal cancer via c-Met receptor regulates
      IAP proteins through Akt signaling. EXPERIMENTAL DESIGN: The level of IAPs and C
      Met mRNA expression was assessed using a quantitative real-time reverse
      transcriptase-PCR (RT-PCR) assay on colorectal normal mucosa (n = 13), adenomas
      (n = 6), and colorectal cancer tumors (n = 50). The role of HGF/C-Met pathway
      through Akt and XIAP was investigated by small interfering RNA (siRNA) and
      quantitative RT-PCR analysis of colorectal cancer lines. RESULTS: Of the IAPs,
      only XIAP showed significant correlation to tumor development and progression.
      XIAP mRNA level in primary colorectal cancer was significantly higher than that
      in colorectal normal mucosa (P = 0.01); liver metastases was significantly higher
      than primary colorectal cancer tumors (P = 0.04); and primary colorectal cancer
      N1/N2 cases were significantly higher than N0 cases (P = 0.008). HGF stimulation
      of colorectal cancer lines enhanced XIAP mRNA expression but not other IAPs.
      Activation of XIAP expression by HGF was inhibited by siRNA targeting Akt1 and
      Akt2. CONCLUSIONS: Activation of C-MET enhances XIAP through the Akt pathway.
      XIAP up-regulation was shown to be correlated to colorectal cancer tumor
      progression. The Akt-XIAP pathway may be a potential molecular target for
      regulating colorectal cancer progression.

PMID- 16278381
TI  - Monocyte chemoattractant protein-1 transfection induces angiogenesis and
      tumorigenesis of gastric carcinoma in nude mice via macrophage recruitment.
AB  - PURPOSE: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that has
      various roles in tumor development and progression. We previously reported that
      expression of MCP-1 is associated with macrophage infiltration and tumor vessel
      density in human gastric carcinomas. The present study was undertaken to obtain
      direct evidence that MCP-1 participates in recruitment of macrophages and
      induction of angiogenesis. EXPERIMENTAL DESIGN: We did transfection experiments
      to analyze the role of MCP-1 in tumorigenicity and angiogenesis in gastric
      carcinoma in nude mice. The human MCP-1 gene cloned into the BCMGS-Neo expression
      vector was transfected into the human gastric carcinoma TMK-1 cell line. We
      examined tumor volumes with the ectopic s.c. xenograft model and tumorigenicity
      with the orthotopic gastric xenograft model. We determined intratumor microvessel
      counts and tumor-infiltrating macrophage counts by immunohistochemical staining.
      RESULTS: There was no difference in in vitro proliferation between MCP-1
      transfected TMK-1 cells and mock-transfected (control) cells; however, MCP-1
      transfectants induced tumor growth in ectopic xenografts and increased
      tumorigenicity and induced lymph node metastases and ascites in orthotopic
      xenografts. In both ectopic and orthotopic xenograft models, strong infiltration
      of macrophages was observed within and around the tumors after implantation of
      MCP-1 transfectants whereas fewer macrophages were seen after inoculation of
      control cells. The microvessel density was significantly higher in tumors
      produced by MCP-1 transfectants than in control tumors. CONCLUSIONS: MCP-1
      produced by gastric carcinoma cells may regulate angiogenesis via macrophage
      recruitment. MCP-1 may be a potential target for antiangiogenic therapy for
      gastric carcinoma.

PMID- 16278382
TI  - Tumor lymphangiogenesis in inflammatory breast carcinoma: a histomorphometric
      study.
AB  - PURPOSE: At the time of diagnosis, metastatic dissemination of tumor cells via
      the lymphatic system has occurred in nearly all patients with inflammatory breast
      cancer (IBC). The objective of this study was twofold: (a) to determine which is
      the most suitable marker of lymph vessels in primary breast tumors and (b) to
      compare histomorphometric lymph vessel variables in IBC and non-IBC. EXPERIMENTAL
      DESIGN: Serial sections of 10 IBCs and 10 non-IBCs were immunostained for D2-40,
      LYVE-1, podoplanin, and PROX-1. Relative lymph vessel area, lymph vessel
      perimeters, and counts and lymphatic endothelial cell proliferation (LECP) were
      then measured in D2-40/Ki-67 double-immunostained sections of 10 normal breast
      tissues, 29 IBCs, and 56 non-IBCs. RESULTS: D2-40 was the most suitable antibody
      for staining peritumoral and intratumoral lymph vessels. D2-40-stained
      intratumoral lymph vessels were present in 80% of non-IBCs and 82.8% of IBCs (P =
      0.76). In non-IBC, lymph vessels located in the tumor parenchyma were smaller and
      less numerous than those at the tumor periphery (P < 0.0001) whereas in IBC,
      intratumoral and peritumoral variables were not significantly different. The mean
      relative tumor area occupied by lymph vessels was larger in IBC than in non-IBC
      (P = 0.01). LECP at the tumor periphery was higher in IBC than in non-IBC: median
      LECP was 5.74% in IBC versus 1.83% in non-IBC (P = 0.005). CONCLUSIONS: The high
      LECP in IBC suggests that lymphangiogenesis contributes to the extensive
      lymphatic spread of IBC.

PMID- 16278383
TI  - Plasmalemmal vesicle associated protein-1 is a novel marker implicated in brain
      tumor angiogenesis.
AB  - PURPOSE: Plasmalemmal vesicle associated protein-1 (PV-1) is up-regulated in the
      endothelium of human glioblastoma. We sought to further characterize the
      expression pattern of PV-1 in human brain tumors and interrogate its role in
      brain tumor angiogenesis. EXPERIMENTAL DESIGN: Quantitative reverse transcription
      PCR and in situ hybridization were used to measure PV-1 expression in a panel of
      46 human brain tumors and related pathologic states. Matrigel tubulogenesis
      assays and cell migration assays were used to show function of PV-1 in primary
      human endothelial cells (HMVEC) under gene knockdown conditions. RESULTS: PV-1 is
      selectively up-regulated in a variety of high-grade human brain tumors, including
      glioblastoma and metastatic carcinoma, as well as other cerebral disorders
      associated with blood-brain barrier disruption, such as acute ischemia.
      Expression levels were reduced in low-grade neoplasia; however, tumors associated
      with the ependyma and choroid plexus, known sites of PV-1 expression, also
      exhibited robust expression. Cerebral expression of PV-1 mRNA was confined to
      endothelial cells in all cases. PV-1 expression was induced in HMVEC cells in
      vitro by exposure to medium conditioned by U87MG and U251MG human brain tumor
      cell lines and by medium supplemented with exogenous vascular endothelial growth
      factor or scatter factor/hepatocyte growth factor. RNA interference-mediated
      inhibition of PV-1 induction in HMVEC cells blocked Matrigel-induced
      tubulogenesis and inhibited cell migration induced by conditioned medium or
      angiogenic growth factors. CONCLUSIONS: Our results confirm that PV-1 is
      preferentially induced in the endothelium of high-grade human brain tumors.
      Inhibition of PV-1 expression is associated with failure of endothelial
      differentiation in vitro. PV-1 represents a novel marker of brain tumor
      angiogenesis and integrity of the blood-brain barrier and is a potential
      therapeutic target.

PMID- 16278384
TI  - Whole-genome allelotyping identified distinct loss-of-heterozygosity patterns in
      mucinous ovarian and appendiceal carcinomas.
AB  - PURPOSE: Mucinous adenocarcinoma of the ovary is one of the common histologic
      types of ovarian cancer. Its pathogenesis is largely unknown. In addition, the
      differential diagnosis of metastatic mucinous carcinomas to the ovaries,
      particularly those originating from the appendix, remains challenging. The
      purpose of this study is to identify molecular biomarkers for mucinous ovarian
      adenocarcinoma and compare them with those of appendiceal origin. EXPERIMENTAL
      DESIGN: Genome-wide loss-of-heterozygosity (LOH) analysis was done on DNA
      isolated from 28 microdissected primary mucinous ovarian carcinomas and five
      appendiceal adenocarcinomas. Markers from high-loss regions were selected for
      further analysis on a total of 32 ovarian and 14 appendiceal cancers. RESULTS:
      High levels of LOH rates (>40%) were detected on chromosome arms 9p, 17p, and 21q
      in mucinous ovarian carcinoma cases. The frequency of allelic loss was similar
      between high-grade and low-grade mucinous ovarian carcinoma cases but was
      significantly higher in ovarian versus appendiceal cases. In addition, LOH rates
      on five chromosomal loci were statistically different between ovarian and
      appendiceal carcinomas. CONCLUSION: A high frequency of LOH can be found in
      mucinous ovarian adenocarcinomas independent of grade. Despite histologic
      similarities between mucinous ovarian carcinomas and metastatic appendiceal
      carcinomas, they have distinct LOH profiles, which may be used for distinguishing
      the two diseases.

PMID- 16278385
TI  - The androgen receptor is significantly associated with vascular endothelial
      growth factor and hypoxia sensing via hypoxia-inducible factors HIF-1a, HIF-2a,
      and the prolyl hydroxylases in human prostate cancer.
AB  - PURPOSE: Hypoxia regulates key biological processes including angiogenesis via
      the transcription factor, hypoxia-inducible factor (HIF). In prostate cancer,
      angiogenesis is also influenced by androgens, and recent cell line studies
      suggest that this effect is partly mediated by HIF. The study aimed to assess
      whether a relationship exists in human prostate cancer between expression of the
      androgen receptor, HIFs, and the key angiogenesis factor, vascular endothelial
      growth factor (VEGF). EXPERIMENTAL DESIGN: A tissue microarray comprised of 149
      radical prostatectomy specimens was constructed. Semiquantitative
      immunohistochemical analysis was used to assess the expression of the androgen
      receptor, VEGF and HIF-1a and 2a, and their regulatory prolyl hydroxylase enzymes
      (PHD1, PHD2, and PHD3). Statistical analysis compared these factors with each
      other and with prostate-specific antigen relapse. RESULTS: There was a
      significant correlation between HIF-1a and HIF-2a expression (P = 0.02), and with
      androgen receptor (P = 0.04 and P < 0.001, respectively) and VEGF expression (P =
      0.05 and P < 0.001, respectively). VEGF was also significantly related to the
      androgen receptor (P = 0.05), whereas PHD2 was inversely related to HIF-2a
      expression. No significant association was shown between HIF-1a or HIF-2a and
      time to prostate-specific antigen recurrence (P = 0.20 and P = 0.94,
      respectively). CONCLUSIONS: These findings confirm the relationship between
      hypoxia and the androgen receptor in prostate cancer, and show for the first
      time, the role of HIF-2a in this disease process. They provide clinical evidence
      to support the recent cell line findings that androgens may regulate VEGF levels
      through the activation of HIF in androgen-sensitive tumors. Inhibition of both
      the HIF pathways may provide new therapeutic options in the management of this
      disease.

PMID- 16278386
TI  - Plitidepsin has a cytostatic effect in human undifferentiated (anaplastic)
      thyroid carcinoma.
AB  - Undifferentiated (anaplastic) thyroid carcinoma is a highly aggressive human
      cancer with very poor prognosis. Although there have been a few studies of
      candidate treatments, the fact that it is an infrequent tumor makes it very
      difficult to design clinical trials. A strong association has been observed
      between undifferentiated thyroid carcinoma and TP53 mutations in numerous
      molecular genetic and expression studies. Plitidepsin (Aplidin, PharmaMar,
      Madrid, Spain) is a novel anticancer compound obtained from a sea tunicate. This
      compound has been reported to induce apoptosis independently of TP53 status. We
      investigated the actions of plitidepsin in human thyroid cancer cells. In initial
      experiments using primary cultured cells from a differentiated (papillary)
      carcinoma, we found that 100 nmol/L plitidepsin induced apoptosis, whereas lower
      doses were cytostatic. Because our aim was to study the effects of plitidepsin at
      clinically relevant concentrations, subsequent experiments were done with a
      dosage regimen reflecting plasma concentrations observed in previously reported
      clinical trials: 100 nmol/L for 4 hours, followed by 10 nmol/L for 20 hours
      (4(100)/20(10) plitidepsin). This plitidepsin dosage regimen blocked the
      proliferation of a primary undifferentiated/anaplastic thyroid carcinoma culture
      obtained in our laboratory and of a commercial cell line (8305C) obtained from an
      undifferentiated thyroid carcinoma; however, it did not induce apoptosis. The
      proportion of cells in the G(1) phase of the cell cycle was greatly increased and
      the proportion in the S/G(2)-M phases greatly reduced, suggesting that
      plitidepsin blocks G(1)-to-S transition. Levels of the cyclin D1/cyclin-dependent
      kinase 4/p21 complex proteins were decreased and, in line with this, the levels
      of unphosphorylated Rb1 increased. The decrease in cell cycle proteins correlated
      with hypoacetylation of histone H3. Finally, we did experiments to assess how
      rapidly tumor cells return to their initial pretreatment proliferative behavior
      after 4(100)/20(10) plitidepsin treatment. Cells from undifferentiated tumors
      needed more than 3 days to recover logarithmic growth, and after 7 days, cell
      number was still significantly lower than in control cultures. 4(100)/20(10)
      plitidepsin inhibited the growth in soft agar. Together, our data show that
      plitidepsin is able to block in vitro cell cycle progression at concentrations
      similar to serum concentrations observed in vivo, and that this effect is
      persistent for several days after plitidepsin removal. Whether plitidepsin will
      prove to be clinically useful in the treatment of undifferentiated thyroid
      cancers remains to be established. However, our results raise the possibility
      that plitidepsin might be effective alone or in combination with radiotherapy
      and/or other drug treatments.

PMID- 16278387
TI  - Cyclooxygenase-2-dependent activation of signal transducer and activator of
      transcription 3 by interleukin-6 in non-small cell lung cancer.
AB  - PURPOSE: Cyclooxygenase-2 (COX-2), phosphorylated signal transducers and
      activators of transcription 3 (STAT3), and interleukin-6 (IL-6) are elevated in
      non-small cell lung cancer (NSCLC). These molecules affect numerous cellular
      pathways, including angiogenesis and apoptosis resistance, and, therefore, may
      act in concert in NSCLC. EXPERIMENTAL DESIGN: We examined IL-6 and phosphorylated
      STAT3 in COX-2-overexpressing [COX-2 sense-oriented (COX-2-S)] NSCLC cells and
      control cells. The effect of IL-6, STAT3, phosphatidylinositol 3-kinase, and
      mitogen-activated protein/extracellular signal-regulated kinase kinase on
      vascular endothelial growth factor (VEGF) production and apoptosis resistance was
      assessed in COX-2-overexpresing cells. RESULTS: We report that NSCLC cells
      overexpressing COX-2 (COX-2-S) have increased IL-6 and phosphorylated STAT3
      expression compared with control cells. IL-6 induced expression of VEGF in NSCLC
      cells. Moreover, blocking IL-6, mitogen-activated protein/extracellular signal
      regulated kinase kinase, or phosphatidylinositol 3-kinase decreased VEGF
      production in COX-2-S cells. The addition of IL-6 to NSCLC cells resulted in
      increased apoptosis resistance. Furthermore, the inhibition of STAT3 or IL-6
      induced apoptosis and reduced survivin expression, a member of the inhibitor of
      apoptosis protein family in COX-2-S cells. CONCLUSIONS: Overall, these findings
      suggest a novel pathway in which COX-2 activates STAT3 by inducing IL-6
      expression. This pathway could contribute to tumor formation by promoting
      survivin-dependent apoptosis resistance and VEGF production. These findings
      provide a rationale for the future development of STAT3, IL-6, and/or COX-2
      targeted therapies for the treatment of lung cancer.

PMID- 16278388
TI  - Basic fibroblast growth factor (FGF-2) overexpression is a risk factor for
      esophageal cancer recurrence and reduced survival, which is ameliorated by
      coexpression of the FGF-2 antisense gene.
AB  - PURPOSE: The basic fibroblast growth factor (FGF-2) gene is bidirectionally
      transcribed to generate overlapping sense and antisense (FGF-AS) mRNAs. FGF-AS
      has been implicated in the post-transcriptional regulation of FGF-2 expression.
      The aim of this study was to characterize FGF-2 and FGF-AS in esophageal cancer
      and to correlate their expression with clinicopathologic findings and outcome.
      EXPERIMENTAL DESIGN: Reverse transcription-PCR was used to study FGF-2 and FGF-AS
      mRNA expression (normalized to glyceraldehyde-3-phosphate dehydrogenase) in 48
      esophageal cancers relative to matched histologically normal esophageal epithelia
      (internal control). We used Cox proportional hazards analysis to calculate hazard
      ratios for recurrence and survival of patients with underexpression relative to
      the overexpression of FGF-2 and/or FGF-AS. RESULTS: Overexpression of FGF-2 mRNA,
      by comparison with tumors underexpressing FGF-2, was associated with
      significantly increased risk for tumor recurrence (hazard ratio, 3.80; 95%
      confidence interval, 1.64-8.76) and reduced overall survival (hazard ratio, 2.11;
      95% confidence interval, 1.0-4.58). When the effects of FGF-2 and FGF-AS were
      considered simultaneously, the association of FGF-2 mRNA overexpression with
      recurrence and mortality was even more pronounced, whereas FGF-AS mRNA
      overexpression was associated with reduced risk for recurrence and improved
      survival. CONCLUSIONS: Overexpression of FGF-2 mRNA is associated with tumor
      recurrence and reduced survival after surgical resection of esophageal cancer and
      that these risks are reduced in tumors coexpressing the FGF-AS mRNA. These data
      support the hypothesis that FGF-AS is a novel tumor suppressor that modulates the
      effect of FGF-2 expression and may have potential clinical application to the
      development of novel therapeutic strategies.

PMID- 16278389
TI  - Immunization using autologous dendritic cells pulsed with the melanoma-associated
      antigen gp100-derived G280-9V peptide elicits CD8+ immunity.
AB  - PURPOSE: To determine the toxicity, maximal tolerated dose, and clinical and
      immunologic response to autologous dendritic cells pulsed with melanoma
      associated antigen gp100-derived G280-9V peptide. PATIENTS AND METHODS: Twelve
      HLA-A*0201(+) patients with advanced melanoma were administered dendritic cells
      pulsed with G280-9V peptide. Cohorts of three patients were administered 5 x
      10(6), 15 x 10(6), and 50 x 10(6) cells i.v. every 3 weeks for six doses
      according to a dose escalation scheme. Three additional patients were treated at
      the highest dose. No additional cytokines or therapies were coadministered. The
      immunogenicity of G280-9V-pulsed dendritic cells was measured by IFN-gamma
      ELISPOT assay, tetramer assay, and (51)Cr release assay comparing prevaccination
      to postvaccination blood samples. Response to treatment was assessed by Response
      Evaluation Criteria in Solid Tumors. RESULTS: CD8(+) immunity to the native G280
      was observed in 8 (67%) patients as measured by ELISPOT and in 12 (100%) patients
      as measured by tetramer assay. Of the 9 patients tested, 9 (100%) had measurable
      high-avidity CTL activity as defined by lysis of allogeneic melanoma lines, which
      coexpress HLA-A*0201 and gp100. The median follow-up of the entire cohort is 43.8
      months. Two (17%) partial responses were observed and 3 (25%) patients had stable
      disease. The median survival of the treated population was 37.6 months. At this
      time, three patients are alive, including one patient who continues to respond
      without additional treatment. CONCLUSION: The high rate of immunization as
      measured by three independent assays and the occurrence of clinical regression
      support continued investigation of G280-9V peptide as a candidate epitope in
      melanoma vaccine formulations.

PMID- 16278391
TI  - Role of activating fibroblast growth factor receptor 3 mutations in the
      development of bladder tumors.
AB  - PURPOSE: Bladder tumors develop through different molecular pathways. Recent
      reports suggest activating mutations of the fibroblast growth factor receptor 3
      (FGFR3) gene as marker for the "papillary" pathway with good prognosis, in
      contrast to the more malignant "carcinoma in situ" (CIS) pathway. The aim of this
      clinical follow-up study was to investigate the role of FGFR3 mutations in
      bladder cancer development in a longitudinal study. EXPERIMENTAL DESIGN: We
      selected 85 patients with superficial bladder tumors, stratified into early
      (stage T(a)/grade 1-2, n = 35) and more advanced (either stage T(1) or grade 3, n
      = 50) developmental stages. The patients were followed prospectively, and
      metachronous tumors were included. We did screening for FGFR3 and TP53 mutations
      by direct bidirectional sequencing and for genome-wide molecular changes with
      microarray technology. RESULTS: A total of 43 of 85 cases (51%) showed activating
      mutations of FGFR3. The mutations were associated with papillary tumors of early
      developmental stage. However, after stratifying for developmental stage, FGFR3
      mutated tumors showed the same malignant potential as wild-type tumors. Tumors
      with concomitant CIS were generally FGFR3 wild type. They were characterized by
      different patterns of chromosomal changes and gene expression signatures compared
      with FGFR3-mutated tumors, indicating different molecular pathways. CONCLUSIONS:
      FGFR3 mutations seem to have a central role in the early development of papillary
      bladder tumors. These tumors follow a common molecular pathway, which is
      different from tumors with concomitant CIS. FGFR3 mutations do not seem to play a
      role in bladder cancer progression.

PMID- 16278390
TI  - The HCCR oncoprotein as a biomarker for human breast cancer.
AB  - PURPOSE: HCCR oncoprotein is reported to be related to tumorigenesis, including
      breast cancer, functioning as a negative regulator of p53. Mice transgenic for
      HCCR developed breast cancers. The objective of this study was to validate the
      HCCR oncoprotein as a candidate biomarker for breast cancer. EXPERIMENTAL DESIGN:
      HCCR expression in breast cancer cells was analyzed by quantitative PCR, ELISA,
      immunohistochemistry, Western blotting, fluorescence-activated cell sorting, and
      confocal microscopy. Epitope areas were determined using mass spectrometry
      through the analysis of time-dependent tryptic fragment patterns of HCCR. HCCR
      expression profiles in breast cancer patient sera were analyzed, and correlations
      with clinicopathologic data and carbohydrate antigen 15-3 (CA15-3) levels were
      determined. RESULTS: HCCR was up-regulated in breast cancer cells and tissues.
      The epitope regions of HCCR recognized by monoclonal antibody (BCS-1) were HFWTPK
      and QQTDFLDIYHAFR. According to fluorescence-activated cell sorting and confocal
      microscopic analysis, BCS-1 was bound to HCCR antigen on the cell surface. Serum
      HCCR concentrations were measured using ELISA from 299 subjects, including 129
      patients with breast cancer, 24 patients with benign breast disease, and 158
      normal volunteers, and comparisons were made to CA15-3. Serologic studies
      revealed an 86.8% sensitivity for HCCR in breast cancer, which was higher than
      21.0% for CA15-3. Eighty-six of 98 (87.8%) patients with breast cancers that were
      negative for CA15-3 were positive for HCCR-1. A positive response rate of 83.3%
      was identified even at early stages for pathologic factors in breast cancer.
      CONCLUSIONS: The HCCR assay has an advantage over CA15-3 in diagnosing breast
      cancer and detecting early stages of the disease.

PMID- 16278392
TI  - Immunogenotype changes prevail in relapses of young children with TEL-AML1
      positive acute lymphoblastic leukemia and derive mainly from clonal selection.
AB  - PURPOSE: Variations of the immunogenotype and TEL deletions in children with TEL
      AML1+ acute lymphoblastic leukemia support the hypothesis that relapses derive
      from a persistent TEL-AML1+ preleukemic/leukemic clone rather than a resistant
      leukemia. We aimed at elucidating the relationship between the immunogenotype
      patterns at diagnosis and relapse as well as their clinical and biological
      relevance. PATIENTS AND METHODS: Immunoglobulin and T-cell receptor gene
      rearrangements were analyzed in 41 children with a TEL-AML1+ acute lymphoblastic
      leukemia and an early (up to 30 months after diagnosis; n = 12) or late (at 30
      months or later; n = 29) disease recurrence by a standardized PCR approach.
      RESULTS: In 68% of the patients (group I), we identified differences in the
      immunogenotype patterns, whereas no changes were observed in the remaining 32%
      (group II). The divergence resulted more often from clonal selection than clonal
      evolution and consisted predominantly of losses (0-6, median 5) and/or gains (0
      4, median 1) of rearrangements. The frequency and number of clonal
      immunoglobulin/T-cell receptor rearrangements in group I was higher at diagnosis
      (2-13, median 5) than at relapse (2-7, median 4), whereas it was the lowest in
      group II (1-5, median 3). Although group I children were younger at diagnosis,
      there was no correlation between particular immunogenotype patterns and remission
      duration. CONCLUSION: These findings imply that the clonal heterogeneity in
      younger children most likely reflects an ongoing high recombinatorial activity in
      the preleukemic/leukemic cells, whereas the more uniform repertoire observed in
      older children mirrors end-stage rearrangement patterns of selected cell clones
      that evolved during the prolonged latency period.

PMID- 16278393
TI  - Methylation assay for the diagnosis of lung cancer on bronchial aspirates: a
      cohort study.
AB  - PURPOSE: Recent studies have detected aberrant promoter methylation of
      adenomatous polyposis coli promoter 1 A (APC), cyclin-dependent kinase inhibitor
      2A (p16(INK4a)), retinoic acid receptor beta2, and RAS association domain family
      protein 1 (RASSF1A) in bronchial aspirates and suggested their use as biomarkers
      for lung cancer diagnostics. The purpose of this study was to validate these
      candidate marker genes in a retrospective cohort study. EXPERIMENTAL DESIGN:
      Bronchial aspirates collected from a cohort comprising 247 patients with
      suspected lung cancer were investigated retrospectively regarding aberrant
      promoter methylation using a quantitative methylation-specific real-time PCR
      (QMSP). RESULTS: Eighty-nine patients were diagnosed with primary lung cancer,
      102 had benign lung disease, and 56 showed miscellaneous other conditions. A
      panel consisting of APC, p16(INK4a), and RASSF1A emerged as useful combination.
      This panel detected aberrant methylation in bronchial aspirates of 22 of 35 (63%)
      and 21 of 44 (44%) centrally and peripherally located primary lung cancers,
      respectively. Bronchial aspirates also showed aberrant methylation in 5 of 7
      (71%) patients with a recurrent lung cancer and in 8 of 30 (27%) cases without
      tumor recurrence. In contrast, only 1 of 102 patients with benign lung disease
      displayed a (false) positive test result. Rarely, aberrant methylation was found
      in patients with other malignancies (3 of 16). The QMSP assay correctly confirmed
      lung cancer in 8 of 12 (67%) cases with an ambiguous cytology. Moreover, it
      disclosed 9 of 26 (35%) of peripheral tumors lacking simultaneous cytologic or
      histologic diagnosis of malignancy. CONCLUSIONS: Our findings suggest that the
      QMSP assay could be applied as a reflex test in cases of suspected lung cancer
      that defy a definite diagnosis by conventional methods. Thus, the assay could be
      a useful diagnostic adjunct especially regarding peripheral tumors.

PMID- 16278394
TI  - Racial differences in prognostic value of adult height for biochemical
      progression following radical prostatectomy.
AB  - PURPOSE: Adult height, as a surrogate of childhood and adolescent hormone
      activity and diet, has been associated with the risk for development and death
      from prostate cancer in predominantly White populations. However, hormonal
      activity and diets vary between races. We examined whether height was
      significantly associated with biochemical progression following radical
      prostatectomy and whether there was an interaction between height and race.
      EXPERIMENTAL DESIGN: Multivariate Cox proportional hazards analysis was used to
      determine if height significantly predicted biochemical progression among 1,503
      men (450 Black and 1,053 White) treated with radical prostatectomy between 1988
      and 2003. We examined for possible interactions between height and race. RESULTS:
      Taller men (>175.3 cm) were significantly younger (P = 0.001), treated in more
      recent years (P = 0.02), had more clinical stage T(1) disease (P = 0.001), and
      were less likely to have extraprostatic extension (P = 0.02) than shorter men (<
      or =175.3 cm). Height was not significantly related to race, preoperative serum
      prostate-specific antigen concentrations, biopsy or pathologic Gleason sum,
      positive surgical margins, seminal vesicle invasion, or lymph node metastasis.
      Height was significantly associated with progression among Black men [relative
      risk (RR), 1.67; 95% confidence interval (95% CI), 1.00-2.79] but not among White
      men (RR, 1.03; 95% CI, 0.77-1.38). The interaction between race and height for
      predicting biochemical progression was statistically significant (P(interaction)
      = 0.05). CONCLUSIONS: There was an interaction between height and race in that
      height predicted progression for Black men but not for White men. The explanation
      for these findings is unclear, although lower insulin-like growth factor-binding
      protein-3 concentrations among Black men may be involved.

PMID- 16278395
TI  - A simple and fast method for the simultaneous detection of nine fibroblast growth
      factor receptor 3 mutations in bladder cancer and voided urine.
AB  - PURPOSE: Mutations in the fibroblast growth factor receptor 3 (FGFR3) occur in
      50% of primary bladder tumors. An FGFR3 mutation is associated with good
      prognosis, illustrated by significantly lower percentage of patients with
      progression and disease-specific mortality. FGFR3 mutations are especially
      prevalent in low grade/stage tumors, with pTa tumors harboring mutations in 85%
      of the cases. These tumors recur in 70% of patients. Efficient FGFR3 mutation
      detection for prognostic purposes and for detection of recurrences in urine is an
      important clinical issue. In this paper, we describe a simple assay for the
      simultaneous detection of nine different FGFR3 mutations. EXPERIMENTAL DESIGN:
      The assay consists of one multiplex PCR, followed by extension of primers for
      each mutation with a labeled dideoxynucleotide. The extended primers are
      separated by capillary electrophoresis, and the identity of the incorporated
      nucleotide indicates the presence or absence of a mutation. RESULTS: The assay
      was found to be more sensitive than single-strand conformation polymorphism
      analysis. Mutations could still be detected with an input of only 1 ng of genomic
      DNA and in a 20-fold excess of wild-type DNA. Moreover, in urine samples from
      patients with a mutant tumor, the sensitivity of mutation detection was 62%.
      CONCLUSIONS: We have developed a fast, easy to use assay for the simultaneous
      detection of FGFR3 mutations, which can be of assistance in clinical decision
      making and as an alternative for the follow-up of patients by invasive cystoscopy
      for the detection of recurrences in urine.

PMID- 16278396
TI  - Mesenchymal stem cell targeting of microscopic tumors and tumor stroma
      development monitored by noninvasive in vivo positron emission tomography
      imaging.
AB  - The aim of this study was to assess the efficacy human mesenchymal stem cells
      (hMSC) for targeting microscopic tumors and suicide gene or cytokine gene
      therapy. Immunodeficient mice were transplanted s.c. with human colon cancer
      cells of HT-29 Inv2 or CCS line, and 3 to 4 days later, i.v. with "tracer" hMSCs
      expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) and enhanced
      green fluorescent protein (EGFP) reporter genes. Subsequently, these tumors were
      examined for specificity and magnitude of HSV1-TK(+), EGFP(+) stem cell
      engraftment and proliferation in tumor stroma by in vivo positron emission
      tomography (PET) with (18)F-labeled 9-(4-fluoro-3-hydroxymethylbutyl)-guanine
      ([(18)F]-FHBG). In vivo PET images of tumors growing for 4 weeks showed the
      presence of HSV1-TK(+) tumor stroma with an average of 0.36 +/- 0.24% ID/g
      [(18)F]-FHBG accumulation. In vivo imaging results were validated by in situ
      correlative histochemical, immunofluorescent, and cytometric analyses, which
      revealed EGFP expression in vWF(+) and CD31(+) endothelial cells of capillaries
      and larger blood vessels, in germinal layer of dermis and hair follicles proximal
      to the s.c. tumor site. These differentiated HSV1-TK(+), GFP(+) endothelial cells
      had limited proliferative capacity and a short life span of <2 weeks in tumor
      fragments transplanted into secondary hosts. We conclude that hMSCs can target
      microscopic tumors, subsequently proliferate and differentiate, and contribute to
      formation of a significant portion of tumor stroma. PET imaging should facilitate
      clinical translation of stem cell-based anticancer gene therapeutic approaches by
      providing the means for in vivo noninvasive whole-body monitoring of trafficking,
      tumor targeting, and proliferation of HSV1-tk-expressing "tracer" hMSCs in tumor
      stroma.

PMID- 16278397
TI  - Allogeneic transplant with reduced intensity conditioning regimens may overcome
      the poor prognosis of B-cell chronic lymphocytic leukemia with unmutated
      immunoglobulin variable heavy-chain gene and chromosomal abnormalities (11q- and
      17p-).
AB  - PURPOSE: To evaluate the efficacy of reduced intensity conditioning (RIC)
      allogeneic transplant in 30 patients with poor-prognosis chronic lymphocytic
      leukemia (CLL) and/or high-risk molecular/cytogenetic characteristics.
      EXPERIMENTAL DESIGN: Eighty-three percent of patients had active disease at the
      moment of transplant. That is, 14 of the 23 patients analyzed (60%) had unmutated
      immunoglobulin variable heavy-chain gene (IgV(H)) status; 8 of 25 patients (32%)
      had 11q-, with four of them also displaying unmutated IgV(H); and six (24%) had
      17p- (five were also unmutated). RESULTS: After a median follow-up of 47.3
      months, all 22 patients alive are disease free; overall survival and event-free
      survival (EFS) at 6 years were 70% and 72%, respectively. According to
      molecular/cytogenetic characteristics, overall survival and EFS for unmutated CLL
      and/or with 11q- aberration (n = 13) were 90% and 92%, respectively, not
      significantly different to those with normal in situ hybridization, 13q- and +12,
      or mutated CLL (n = 7). All six patients with 17p deletion were transplanted with
      active disease, including three with refractory disease; all except one reached
      complete remission after the transplant and two are alive and disease free.
      Nonrelapse mortality (NRM) was 20%; more than two lines before transplant is an
      independent prognostic factor for NRM (P = 0,02), EFS (P = 0.02), and overall
      survival (P = 0.01). Patients older than 55 years have a higher risk of NRM
      (hazard ratio, 12.8; 95% confidence interval, 1.5-111). Minimal residual disease
      was monitored by multiparametric flow cytometry in 21 patients. Clearance of
      CD79/CD5/CD19/CD23 cells in bone marrow was achieved in 68% and 94% of the
      patients at days 100 and 360, respectively. CONCLUSION: According to these
      results, RIC allogeneic transplant could overcome the adverse prognosis of
      patients with unmutated CLL as well as those with 11q- or 17p-.

PMID- 16278398
TI  - MRP3, BCRP, and P-glycoprotein activities are prognostic factors in adult acute
      myeloid leukemia.
AB  - PURPOSE: P-Glycoprotein (Pgp) is associated with poor outcome in acute myeloid
      leukemia (AML). We have investigated other ATP-binding cassette proteins such as
      BCRP, MRP1, MRP2, MRP3, and MRP5 for their potential implication in
      chemoresistance. EXPERIMENTAL DESIGN AND RESULTS: Eighty five AML patient samples
      were analyzed in this study. First, MRP3 function was higher in patients which
      had a high level of leukocytes (P = 0.01), a M5 FAB subtype (P = 0.04), and an
      intermediate or poor cytogenesis (P = 0.05). BCRP activity was not correlated
      with clinical or biological variables, but high Pgp activity was correlated with
      the following variables: CD34 expression (P = 0.002), FAB subtype (P = 0.002),
      intermediate or poor cytogenesis (P = 0.02), and elderly patients (P = 0.03).
      Second, Pgp, MRP3, and BCRP activities were correlated with complete remission (P
      = 0.02, P = 0.04, and P = 0.04, respectively), disease-free survival (P = 0.02, P
      = 0.03, and P = 0.25, respectively), and overall survival (P = 0.04, P = 0.04,
      and P = 0.05, respectively) in multivariate analysis. The patient samples
      expressing one or none of these Pgp, MRP3, or BCRP functional proteins have a
      better prognosis than the patients expressing two or three of these functional
      proteins (complete remission, P = 0.02; disease-free survival, P = 0.01; overall
      survival, P < 0.001). CONCLUSIONS: BCRP and MRP3 may also be involved in
      chemoresistance in AML, especially MRP3 in patients with M5 FAB. Additional
      modulation of BCRP or MRP3 to Pgp modulation may be necessary in some patients in
      order to improve the treatment outcome.

PMID- 16278399
TI  - Patupilone induced vascular disruption in orthotopic rodent tumor models detected
      by magnetic resonance imaging and interstitial fluid pressure.
AB  - PURPOSE: Evaluation of vascular disruptive activity in orthotopic models as
      potential surrogate biomarkers of tumor response to the microtubule-stabilizing
      agent patupilone. EXPERIMENTAL DESIGN: Mice bearing metastatic B16/BL6 melanoma
      and rats bearing mammary BN472 tumors received vehicle or efficacious patupilone
      doses (4 and 0.8-1.5 mg/kg i.v., respectively). Tumor vascularity assessment by
      dynamic contrast-enhanced or dynamic susceptibility contrast magnetic resonance
      imaging and interstitial fluid pressure (IFP) occurred at baseline, 2 days (mice
      and rats), and 6 days (rats) after treatment and were compared with histologic
      measurements and correlated with tumor response. RESULTS: In B16/BL6 metastases,
      patupilone (4 mg/kg) induced a 21 +/- 5% decrease (P < 0.001) in tumor blood
      volume and a 32 +/- 15% decrease (P = 0.02) in IFP after 2 days and reduced tumor
      growth and vessel density (>42%) after 2 weeks (P < or = 0.014). Patupilone dose
      dependently inhibited BN472 tumor growth (day 6) and reduced IFP on days 2 and 6
      (-21% to -70%), and the percentage change in IFP correlated (P < 0.01) with the
      change in tumor volume. In both models, histology and vascular casts confirmed
      decreases in tumor blood volume. One patupilone (0.8 mg/kg) administration
      decreased (P < 0.01) tumor IFP (54 +/- 4%), tumor blood volume (50 +/- 6%), and
      vessel diameter (40 +/- 11%) by day 6 but not the apparent diffusion coefficient,
      whereas histology showed that apoptosis was increased 2.4-fold and necrosis was
      unchanged. Apoptosis correlated negatively (P < 0.001) with IFP, tumor blood
      volume, and tumor volume, whereas tumor blood volume and IFP were correlated
      positively (P = 0.0005). CONCLUSIONS: Vascular disruptive effects of patupilone
      were detected in situ using dynamic contrast-enhanced or dynamic susceptibility
      contrast magnetic resonance imaging and IFP. Changes in IFP preceded and
      correlated with tumor response, suggesting that IFP may be a surrogate biomarker
      for patupilone efficacy.

PMID- 16278400
TI  - The role of S100A6 in pancreatic cancer development and its clinical implication
      as a diagnostic marker and therapeutic target.
AB  - Recent microarray analyses showed that the S100 family contains members that are
      candidate diagnostic markers or therapeutic targets. In the present study, to
      evaluate the involvement of S100A6 in pancreatic cancer and its clinical
      usefulness for diagnosis, we examined S100A6 mRNA expression in pancreatic
      tissues and pancreatic juice from patients with different pancreatic diseases. To
      investigate the role of S100A6 in carcinogenesis of pancreatic cancer and the
      potential of S100A6 as a diagnostic marker for early detection of pancreatic
      cancer, we did immunohistochemistry and microdissection-based mRNA analysis of
      pancreatic normal ducts, pancreatic intraepithelial neoplasias, and invasive
      ductal carcinomas. We also used in vitro experiments and microarray analysis with
      RNA interference to evaluate the functional role of S100A6 and its potential as a
      therapeutic target for pancreatic cancer. S100A6 mRNA levels were significantly
      higher in carcinoma specimens than in nonneoplastic tissues. In pancreatic juice,
      there was a significant difference in S100A6 expression between patients with
      carcinoma and those with nonneoplastic disease. Receiver operating characteristic
      curves revealed that S100A6 might be a useful marker for diagnosis of pancreatic
      cancer. Immunohistochemistry and microdissection-based analysis showed
      differential expression of S100A6 among normal ducts, pancreatic intraepithelial
      neoplasias, and invasive ductal carcinomas. In vitro data showed that inhibition
      of S100A6 decreased proliferation and invasiveness of cancer cells, and these
      findings were supported by microarray data. Our present results suggest that
      quantitation of S100A6 mRNA is a promising tool for diagnosis of pancreatic
      cancer, and that S100A6 may be a promising therapeutic target for pancreatic
      cancer.

PMID- 16278401
TI  - Pharmacokinetics and tolerability of a single dose of DN-101, a new formulation
      of calcitriol, in patients with cancer.
AB  - BACKGROUND: Intermittent administration allows substantial dose escalation of
      calcitriol but limited bioavailability of the commercially available formulations
      at high doses is limiting. In this dose escalation study, we sought to evaluate
      the tolerability and pharmacokinetics of a single oral dose of DN-101, a high
      dose calcitriol formulation. METHODS: DN-101 doses were escalated in sequential
      groups of three to six patients with advanced solid tumors. Dose-limiting
      toxicity was defined as grade > or =2 hypercalcemia or grade > or =3 persistent
      treatment-related toxicities. Single-dose administration of 15, 30, 60, 75, 90,
      105, 135, and 165 mug was tested. RESULTS: Thirty-eight patients were enrolled in
      2002 and 2003. The median age was 70 years (range, 44-91 years). Dose escalation
      was stopped at the 165 microg level when the number of capsules required at one
      time reached 11. No dose-limiting toxicities occurred. Transient and self-limited
      grade 3 toxicities were hyponatremia (2) and proteinuria (1). A dose-proportional
      increase in peak concentration (C(max)) and area under the concentration curve
      (AUC) was seen across the full range of DN-101 doses tested. At the 165 microg
      dose, C(max) was 6.21 +/- 1.99 ng/mL, AUC(0-24) was 41.3 +/- 9.77 ng h/mL, AUC(0
      infinity) was 55.4 +/- 8.44, and half-life (T(1/2)) was 16.2 hours. CONCLUSIONS:
      At doses between 15 and 165 microg, DN-101 exhibits linear pharmacokinetics. At
      165 microg, DN-101 achieves systemic exposure that is 5- to 8-fold higher than
      that achieved with commercial formulations of calcitriol, which makes DN-101
      comparable to that required for antitumor activity in vivo in a murine squamous
      cell carcinoma model.

PMID- 16278402
TI  - Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan.
AB  - PURPOSE: Milk thistle (Silybum marianum) is one of the most commonly used herbal
      therapies, and its principal constituent silybin significantly inhibits
      cytochrome P450 isoform 3A4 (CYP3A4) and UDP glucuronosyltransferase isoform 1A1
      (UGT1A1) in vitro. Here, we investigated whether milk thistle affects the
      pharmacokinetics of irinotecan, a substrate for CYP3A4 and UGT1A1, in humans.
      EXPERIMENTAL DESIGN: Six cancer patients were treated with irinotecan (dose, 125
      mg/m(2)) given as a 90-minute infusion once every week. Four days before the
      second dose, patients received 200 mg milk thistle, thrice a day, for 14
      consecutive days. Pharmacokinetic studies of irinotecan and its metabolites 7
      ethyl-10-hydroxycamptothecin (SN-38), 7-ethyl-10-[3,4,5-trihydroxy-pyran-2
      carboxylic acid]-camptothecin (SN-38-glucuronide), and 7-ethyl-10-[4-N-(5
      aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin were done during the
      first three irinotecan administrations. RESULTS: Short-term (4 days) or more
      prolonged intake of milk thistle (12 days) had no significant effect on
      irinotecan clearance (mean, 31.2 versus 25.4 versus 25.6 L/h; P = 0.16). The area
      under the curve ratio of SN-38 and irinotecan was slightly decreased by milk
      thistle (2.58% versus 2.23% versus 2.17%; P = 0.047), whereas the relative extent
      of glucuronidation of SN-38 was similar (10.8 versus 13.5 versus 13.1; P = 0.64).
      Likewise, the area under the curve ratio of 7-ethyl-10-[4-N-(5-aminopentanoic
      acid)-1-piperidino]-carbonyloxycamptothecin and irinotecan was unaffected by milk
      thistle (0.332 versus 0.285 versus 0.337; P = 0.53). The maximum plasma
      concentrations of silybin ranged between 0.0249 and 0.257 micromol/L.
      CONCLUSIONS: Silybin concentrations after intake of milk thistle are too low to
      significantly affect the function of CYP3A4 and UGT1A1 in vivo, indicating that
      milk thistle is unlikely to alter the disposition of anticancer drugs metabolized
      by these enzymes.

PMID- 16278403
TI  - A phase I study of the dolastatin-15 analogue tasidotin (ILX651) administered
      intravenously daily for 5 consecutive days every 3 weeks in patients with
      advanced solid tumors.
AB  - PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicity, and
      pharmacokinetics of the dolastatin-15 analogue, tasidotin (ILX651), when
      administered i.v. daily for 5 days every 3 weeks. EXPERIMENTAL DESIGN: Thirty-six
      patients with advanced solid tumors received a total of 114 courses through eight
      dose levels ranging from 2.3 to 36.3 mg/m(2). Pharmacokinetic samples were
      collected in cycle 1. RESULTS: Neutropenia was the principal dose-limiting
      toxicity at 36.3 mg/m(2)/d along with grade 3 ileus and elevated aspartate amino
      transaminase/alanine amino transaminase (n = 1). At the maximum tolerated dose,
      27.3 mg/m(2), 4 of 14 patients experienced dose-limiting grade 4 neutropenia. The
      other principal toxicities consisted of mild-to-moderate elevated transaminases,
      alopecia, fatigue, and nausea. One patient with melanoma metastatic to liver and
      bone treated at 15.4 mg/m(2)/d experienced a complete response and received 20
      courses of tasidotin. Two other patients with melanoma had mixed responses of
      cutaneous metastases at 27.3 mg/m(2)/d associated with either stable or
      progressive visceral disease. In addition, nine patients had stable disease.
      There was no accumulation of tasidotin following repeated daily dosing. Tasidotin
      decayed from plasma in a biphasic fashion with a half-life of <45 minutes in most
      cases. CONCLUSION: The maximum tolerated dose and recommended phase II dose for
      tasidotin when administered on this schedule was 27.3 mg/m(2)/d. The favorable
      toxicity profile of tasidotin compared with other antitubulin agents
      (particularly the lack of severe cumulative neuropathy, peripheral edema, and
      fatigue), the observed antitumor activity of tasidotin, and its novel mechanism
      of action support further disease-directed evaluations of this agent on this 5
      day schedule every 3 weeks.

PMID- 16278404
TI  - Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating
      agent, combined with cytarabine in patients with refractory leukemia.
AB  - PURPOSE: Cloretazine (VNP40101M) is a novel sulfonylhydrazine alkylating agent
      with significant antileukemia activity. A phase I study of cloretazine combined
      with cytarabine (1-beta-d-arabinofuranosylcytosine, ara-C) was conducted in
      patients with refractory disease. DESIGN: Ara-C was given i.v. at a fixed dose of
      1.5 gm/m(2)/d by continuous infusion for 4 days (patients ages <65 years at time
      of diagnosis) or 3 days (patients ages > or =65 years). Cloretazine was given
      i.v. over 15 to 60 minutes on day 2 at a starting dose of 200 mg/m(2), with
      escalation in 100 mg/m(2) increments in cohorts of three to six patients until a
      maximum tolerated dose was established. The DNA repair enzyme O(6)-alkylguanine
      DNA alkyltransferase (AGT) was measured at baseline. RESULTS: Forty patients,
      including 32 with acute myeloid leukemia, received 47 courses of treatment.
      Complete responses were seen at cloretazine dose levels of > or =400 mg/m(2) in
      10 of 37 (27%) evaluable patients, and in this patient subset, AGT activity was
      significantly lower in patients that responded to treatment than in patients who
      did not (P < or = 0.027). Dose-limiting toxicities (gastrointestinal and
      myelosuppression) were seen with 500 and 600 mg/m(2) of cloretazine combined with
      the 4-day ara-C schedule but not seen with the 3-day schedule. CONCLUSION: The
      recommended cloretazine dose schedule for future studies is 600 mg/m(2) combined
      with 1.5 gm/m(2)/d continuous infusion of ara-C for 3 days. The cloretazine and
      ara-C regimen has significant antileukemic activity. AGT activity may be a
      predictor of response to cloretazine.

PMID- 16278405
TI  - Phase I and pharmacokinetic study of the dolastatin-15 analogue tasidotin
      (ILX651) administered intravenously on days 1, 3, and 5 every 3 weeks in patients
      with advanced solid tumors.
AB  - PURPOSE: To determine the maximum tolerated dose (MTD), dose-limiting toxicity
      (DLT), and pharmacokinetics of tasidotin (ILX651), a dolastatin-15 analogue, when
      administered on days 1, 3, and 5 every 3 weeks in patients with advanced solid
      tumors. PATIENTS AND METHODS: Thirty-two patients were treated with 92 courses of
      tasidotin through seven dose levels determined by a modified Fibonacci scheme
      ranging from 3.9 to 45.7 mg/m(2). Pharmacokinetic samples were collected during
      the first course. RESULTS: Neutropenia was the principal DLT at the 45.7
      mg/m(2)/d dose level. In addition, one patient also experienced grade 3
      neutropenia complicated with grade 3 esophageal candidiasis and grade 3
      dehydration. Only 1 of 11 patients treated at the MTD, 34.4 mg/m(2), experienced
      dose-limiting neutropenia. Other common, drug-related toxicities included mild to
      moderate fatigue, anemia, nausea, anorexia, emesis, alopecia, and diarrhea. The
      best observed antitumor response consisted of stable disease and was noted in 10
      patients (31%); the median duration on study for those patients with stable
      disease was 99.5 days compared with 37.5 days for those patients with progressive
      disease. Tasidotin plasma concentrations declined biphasically with an effective
      half-life of < or =55 minutes, and approximately 11% was excreted unchanged in
      the urine. CONCLUSION: The recommended dose for phase II studies and the MTD when
      tasidotin is administered on days 1, 3, and 5 every 3 weeks is 34.4 mg/m(2). The
      favorable toxicity profile of tasidotin compared with other antitubulin agents,
      including other dolastatin analogues, and its novel mechanism of action support
      further disease-directed evaluation of this agent.

PMID- 16278406
TI  - A phase I and pharmacokinetic study of paclitaxel poliglumex (XYOTAX),
      investigating both 3-weekly and 2-weekly schedules.
AB  - PURPOSE: To determine the safety, maximum tolerated dose, pharmacokinetics, and
      toxicities associated with administration of paclitaxel poliglumex (PPX, XYOTAX,
      Cell Therapeutics, Inc., Bresso, Italy) given on either 3-weekly or 2-weekly
      schedule. EXPERIMENTAL DESIGN: Nineteen patients were investigated on the 3
      weekly phase Ia study and 11 patients on the 2-weekly phase Ib study. Dose
      escalation starting with 100% increments and one patient per dose level was
      modulated in accordance with the observed toxicities. Conjugated and unconjugated
      paclitaxel were measured in plasma. RESULTS: Dose-limiting toxicity of
      neutropenia was encountered at 266 mg/m(2) (paclitaxel equivalents) in phase Ia
      and the maximum tolerated dose was 233 mg/m(2). Neuropathy was dose-limiting in
      phase Ib with a maximum tolerated dose of 177 mg/m(2). Pharmacokinetic
      investigations indicated a prolonged half-life of >100 hours for conjugated
      taxanes. Plasma concentrations of unconjugated paclitaxel were similar to those
      following administration of an equivalent dose of Taxol. Two partial responses
      were observed, one in a patient with mesothelioma at 177 mg/m(2) in phase Ia and
      one in a patient with gastric carcinoma at 175 mg/m(2) in phase Ib. CONCLUSION:
      PPX is a water-soluble paclitaxel-polymer conjugate with a prolonged half-life
      and limited volume of distribution. Dose-limiting toxicities were neutropenia and
      neuropathy. PPX showed activity in this patient population.

PMID- 16278407
TI  - Molecular study of malignant gliomas treated with epidermal growth factor
      receptor inhibitors: tissue analysis from North American Brain Tumor Consortium
      Trials 01-03 and 00-01.
AB  - PURPOSE: We investigated the molecular effect of the epidermal growth factor
      receptor (EGFR) inhibitors erlotinib and gefitinib in vivo on all available
      tumors from patients treated on North American Brain Tumor Consortium trials 01
      03 and 00-01 for recurrent or progressive malignant glioma. EXPERIMENTAL DESIGN:
      EGFR expression and signaling during treatment with erlotinib or gefitinib were
      analyzed by Western blot and compared with pre-erlotinib/gefitinib-exposed tissue
      or unexposed controls. Tumors were also analyzed for EGFR mutations and for other
      genomic abnormalities by array-based comparative genomic hybridization. Clinical
      data were used to associate molecular features with tumor sensitivity to
      erlotinib or gefitinib. RESULTS: Erlotinib and gefitinib did not markedly affect
      EGFR activity in vivo. No lung signature mutations of EGFR exons 18 to 21 were
      observed. There was no clear association between erlotinib/gefitinib sensitivity
      and deletion or amplification events on array-based comparative genomic
      hybridization analysis, although novel genomic changes were identified.
      CONCLUSIONS: As erlotinib and gefitinib were generally ineffective at markedly
      inhibiting EGFR phosphorylation in these tumors, other assays may be needed to
      detect molecular effects. Additionally, the mechanism of erlotinib/gefitinib
      sensitivity likely differs between brain and lung tumors. Finally, novel genomic
      changes, including deletions of chromosomes 6, 21, and 22, represent new targets
      for further research.

PMID- 16278408
TI  - Phase I trial of a monoclonal antibody specific for alphavbeta3 integrin (MEDI
      522) in patients with advanced malignancies, including an assessment of effect on
      tumor perfusion.
AB  - At present, a variety of agents targeting tumor angiogenesis are under clinical
      investigation as new therapies for patients with cancer. Overexpression of the
      alpha(v)beta(3) integrin on tumor vasculature has been associated with an
      aggressive phenotype of several solid tumor types. Murine models have shown that
      antibodies targeting the alpha(v)beta(3) integrin can affect tumor vasculature
      and block tumor formation and metastasis. These findings suggest that antibodies
      directed at alpha(v)beta(3) could be investigated in the treatment of human
      malignancies. The current phase I dose escalation study evaluated the safety of
      MEDI-522, a monoclonal antibody specific for the alpha(v)beta(3) integrin, in
      patients with advanced malignancies. Twenty-five patients with a variety of
      metastatic solid tumors were treated with MEDI-522 on a weekly basis with doses
      ranging from 2 to 10 mg/kg/wk. Adverse events were assessed weekly;
      pharmacokinetic studies were done; and radiographic staging was done every 8
      weeks. In addition, dynamic computed tomography imaging was done at baseline and
      at 8 weeks in patients with suitable target lesions amenable to analysis, to
      potentially identify the effect of MEDI-522 on tumor perfusion. Treatment was
      well tolerated, and a maximum tolerated dose was not identified by traditional
      dose-limiting toxicities. The major adverse events observed were grade 1 and 2
      infusion-related reactions (fever, rigors, flushing, injection site reactions,
      and tachycardia), low-grade constitutional and gastrointestinal symptoms
      (fatigue, myalgias, and nausea), and asymptomatic hypophosphatemia. Dynamic
      computed tomography imaging suggested a possible effect on tumor perfusion with
      an increase in contrast mean transit time from baseline to the 8-week evaluation
      with increasing doses of MEDI-522. No complete or partial responses were
      observed. Three patients with metastatic renal cell cancer experienced prolonged
      stable disease (34 weeks, >1 and >2 years) on treatment. With this weekly
      schedule of administration, and in the doses studied, MEDI-522 seems to be
      without significant toxicity, may have effects on tumor perfusion, and may have
      clinical activity in renal cell cancer. These findings suggest the MEDI-522 could
      be further investigated as an antiangiogenic agent for the treatment of cancer.

PMID- 16278409
TI  - Phase II trial of the O6-alkylguanine DNA alkyltransferase inhibitor O6
      benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea in advanced melanoma.
AB  - PURPOSE: 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) induces DNA damage via a
      chloroethyl adduct at the O(6) position of guanine, which can be repaired by O(6)
      alkylguanine DNA alkyltransferase (AGT) expressed in melanoma. We postulated that
      the addition of O(6) benzylguanine (O(6)BG), a potent inactivator of AGT, would
      improve the clinical response to BCNU in melanoma. EXPERIMENTAL DESIGN: Patients
      had measurable disease, adequate organ function, and a corrected Diffusing
      capacity of the lung for carbon monoxide (DLCO) of > or =70% predicted. They were
      accrued into two cohorts based on prior chemotherapy. O(6)BG (120 mg/m(2)) was
      administered i.v. followed by BCNU (40 mg/m(2)) on an outpatient basis.
      Peripheral blood mononuclear cells (PBMC) were collected pre- and 18 hours post
      O(6)BG to analyze AGT depletion. Treatment was every 6 weeks, and clinical
      response was assessed after every two cycles. RESULTS: Forty-two patients were
      enrolled, 22 of these patients were chemotherapy-naive. In the chemotherapy-naive
      cohort, there was a patient with a complete response (CR), 4 with stable disease
      (SD), 13 with progressive disease (PD), and 4 nonevaluable patients; the median
      time to progression was 80 days and the median survival was 211 days. In the
      prior-chemotherapy cohort, there were no responses, 3 SD, 15 PD, and 2
      nonevaluable patients; median time to progression was 54 days and median survival
      was 120 days. AGT was depleted from PBMC in the 15 patients tested. Grades 3 to 4
      myelosuppression was seen in 57% of patients; toxicities were similar between the
      two cohorts. CONCLUSIONS: O(6)BG/BCNU was successfully administered on an
      outpatient basis and depleted AGT from PBMC. However, significant
      myelosuppression was observed and the clinical outcome was not improved.
      Alternative mechanisms of resistance to melanoma cell death need to be
      investigated.

PMID- 16278410
TI  - Phase 1 study of weekly polyethylene glycol-camptothecin in patients with
      advanced solid tumors and lymphomas.
AB  - PURPOSE: To determine the maximal tolerated dose and dose-limiting toxicities
      (DLT) of pegamotecan (polyethylene glycol-camptothecin) in patients with advanced
      malignancies when administered in cycles of once weekly for 3 of 4 weeks.
      EXPERIMENTAL DESIGN: Eligible patients had advanced solid tumors that failed to
      respond to standard therapy or for which no standard therapy was available,
      including also the following criteria: measurable disease, Eastern Cooperative
      Oncology Group performance status of < or =2, and acceptable organ function.
      Pegamotecan was administered as a 60-minute infusion, with successive patient
      cohorts receiving escalating doses from 800 to 4,300 mg/m(2). The primary end
      point was to determine the maximal tolerated dose. Other end points were
      toxicity, pharmacokinetics, pharmacodynamics, and efficacy. Pharmacokinetic
      analysis measured free camptothecin. Pharmacodynamic analysis correlated drug
      effects with pegamotecan dose and pharmacokinetic variables. RESULTS: Twenty
      seven patients were enrolled. The maximal tolerated dose was 3,240 mg/m(2). Grade
      4 neutropenia, the DLT, was noted in two of four patients treated at 4,300
      mg/m(2). Other grade 3 and 4 toxicities were anemia, thrombocytopenia, fatigue,
      prolonged partial thromboplastin time, hemorrhagic cystitis, dysuria, and urinary
      frequency. Pharmacokinetic analysis showed the apparent terminal elimination half
      life to be 46 +/- 12.8 hours. Pharmacodynamic analysis showed that hematuria
      occurred in 8 of 15 patients with an area under the curve extrapolated to
      infinity (AUC(0-infinity)) > 20 ng h/mL and 0 of 10 patients with an AUC(0
      infinity) < or = 20 ng h/mL. Unconfirmed partial responses were observed in two
      patients, one with metastatic small bowel adenocarcinoma and the other with
      metastatic esophageal cancer. CONCLUSIONS: The maximal tolerated dose of
      pegamotecan when administered weekly for 3 of 4 weeks is 3,240 mg/m(2). The DLT
      was neutropenia. Among nonhematologic toxicities, the incidence of
      gastrointestinal toxicity was low, but genitourinary toxicity seems to occur in
      the same effective dose range as noted with native camptothecin in earlier trials
      (27-43 mg/m(2)). The observed antitumor activity suggests that pegamotecan has
      single-agent activity and merits further investigation in phase 2 studies.

PMID- 16278411
TI  - Adaptive signature design: an adaptive clinical trial design for generating and
      prospectively testing a gene expression signature for sensitive patients.
AB  - PURPOSE: A new generation of molecularly targeted agents is entering the
      definitive stage of clinical evaluation. Many of these drugs benefit only a
      subset of treated patients and may be overlooked by the traditional, broad
      eligibility approach to randomized clinical trials. Thus, there is a need for
      development of novel statistical methodology for rapid evaluation of these
      agents. EXPERIMENTAL DESIGN: We propose a new adaptive design for randomized
      clinical trials of targeted agents in settings where an assay or signature that
      identifies sensitive patients is not available at the outset of the study. The
      design combines prospective development of a gene expression-based classifier to
      select sensitive patients with a properly powered test for overall effect.
      RESULTS: Performance of the adaptive design, relative to the more traditional
      design, is evaluated in a simulation study. It is shown that when the proportion
      of patients sensitive to the new drug is low, the adaptive design substantially
      reduces the chance of false rejection of effective new treatments. When the new
      treatment is broadly effective, the adaptive design has power to detect the
      overall effect similar to the traditional design. Formulas are provided to
      determine the situations in which the new design is advantageous. CONCLUSION:
      Development of a gene expression-based classifier to identify the subset of
      sensitive patients can be prospectively incorporated into a randomized phase III
      design without compromising the ability to detect an overall effect.

PMID- 16278412
TI  - Therapeutic advantage of pretargeted radioimmunotherapy using a recombinant
      bispecific antibody in a human colon cancer xenograft.
AB  - PURPOSE: To assess if pretargeting, using a combination of a recombinant
      bispecific antibody (bsMAb) that binds divalently to carcinoembryonic antigen
      (CEA) and monovalently to the hapten histamine-succinyl-glycine and a (90)Y
      peptide, improves therapeutic efficacy in a human colon cancer-nude mouse
      xenograft compared with control animals given (90)Y-humanized anti-CEA
      immunoglobulin G (IgG). EXPERIMENTAL DESIGN: Clearance and biodistribution were
      monitored by whole-body readings and necropsy. Animals were monitored for 34
      weeks with a determination of residual disease and renal pathology in survivors.
      Hematologic toxicity was assessed separately in non-tumor-bearing NIH Swiss mice.
      RESULTS: Hematologic toxicity was severe at doses of 100 to 200 microCi of (90)Y
      IgG, yet mild in the pretargeted animals given 500 or 700 microCi of the (90)Y
      peptide. Evidence of end-stage renal disease was found at 900 microCi of the
      pretargeted (90)Y-peptide whereas animals given 700 microCi showed only mild
      renal pathology, similar to that seen in control animals given (90)Y-IgG.
      Biodistribution data indicated that the average amount of tumor radioactivity by
      a 700-microCi dose of the pretargeted peptide over a 96-hour period was increased
      2.5-fold (48 microCi/g) compared with 150 microCi of (90)Y-IgG (18.9 microCi/g).
      At these doses, survival (i.e., time to progression to 2.5 cm(3)) was
      significantly improved (P < 0.04) compared with (90)Y-IgG, with ablation of about
      one third of the tumors, whereas viable tumor was present in all of the (90)Y-IgG
      treated animals. CONCLUSION: Pretargeting increases the amount of radioactivity
      delivered to colorectal tumors sufficiently to improve the therapeutic index and
      responses as compared with conventional radioimmunotherapy.

PMID- 16278413
TI  - Oncolytic herpes simplex virus vector g47delta in combination with androgen
      ablation for the treatment of human prostate adenocarcinoma.
AB  - PURPOSE: The use of oncolytic herpes simplex virus type 1 is a promising stategy
      for cancer treatment. We constructed herpes simplex virus type 1 vector G47Delta
      by deleting the alpha47 gene and the promoter region of US11 from G207. We now
      report studies demonstrating the potential of G47Delta as a therapeutic modality
      for prostate cancer in combination with androgen ablation. EXPERIMENTAL DESIGN:
      The cytopathic activities of G47Delta at low multiplicities of infection was
      tested in human prostate cancer cell lines LNCaP, PC-3, and DU145 in vitro. Two
      androgen-dependent mouse s.c. tumor models, murine TRAMP and human HONDA, were
      used to investigate the in vivo efficacy of G47Delta in combination with androgen
      ablation. RESULTS: G47Delta at low multiplicities of infection showed more rapid
      tumor cell killing than G207 in LNCaP and DU145 in vitro and showed a 22-fold
      higher virus yield in a single-step growth experiment. In vivo, G47Delta
      treatment resulted in reduced tumor growth of established s.c. TRAMP and HONDA
      tumors and inhibited the growth of recurrent HONDA tumors that once regressed by
      androgen ablation therapy. In both TRAMP and HONDA tumor xenografts, the
      combination therapy of G47Delta with androgen ablation led to significantly
      enhanced inhibition of the tumor growth and prolonged survival. CONCLUSIONS:
      These results suggest that oncolytic virus therapy with G47Delta can be usefully
      combined with androgen ablation therapy for the treatment of prostate cancer.

PMID- 16278414
TI  - Dendritic cells fused with allogeneic colorectal cancer cell line present
      multiple colorectal cancer-specific antigens and induce antitumor immunity
      against autologous tumor cells.
AB  - The aim of antitumor immunotherapy is to induce CTL responses against autologous
      tumors. Previous work has shown that fusion of human dendritic cells and
      autologous tumor cells induce CTL responses against autologous tumor cells in
      vitro. However, in the clinical setting of patients with colorectal carcinoma, a
      major difficulty is the preparation of sufficient amounts of autologous tumor
      cells. In the present study, autologous dendritic cells from patients with
      colorectal carcinoma were fused to allogeneic colorectal tumor cell line, COLM-6
      (HLA-A2(-)/HLA-24(-)), carcinoembryonic antigen (CEA)(+), and MUC1(+) as an
      alternative strategy to deliver shared colorectal carcinoma antigens to dendritic
      cells. Stimulation of autologous T cells by the fusion cells generated with
      autologous dendritic cells (HLA-A2(+) and/or HLA-A24(+)) and allogeneic COLM-6
      resulted in MHC class I- and MHC class II-restricted proliferation of CD4(+) and
      CD8(+) T cells, high levels of IFN-gamma production in both CD4(+) and CD8(+) T
      cells, and the simultaneous induction of CEA- and MUC1-specific CTL responses
      restricted by HLA-A2 and/or HLA-A24. Finally, CTL induced by dendritic
      cell/allogeneic COLM-6 fusion cells were able to kill autologous colorectal
      carcinoma by HLA-A2- and/or HLA-A24-restricted mechanisms. The demonstration of
      CTL activity against shared tumor-associated antigens using an allogeneic tumor
      cell line, COLM-6, provides that the presence of alloantigens does not prevent
      the development of CTL with activity against autologous colorectal carcinoma
      cells. The fusion of allogeneic colorectal carcinoma cell line and autologous
      dendritic cells could have potential applicability to the field of antitumor
      immunotherapy through the cross-priming against shared tumor antigens and
      provides a platform for adoptive immunotherapy.

PMID- 16278415
TI  - Chemokine C receptor 7 expression and protection of circulating CD8+ T
      lymphocytes from apoptosis.
AB  - Chemokine C receptor 7 (CCR7) expression is important for lymphocyte homing to
      tissues. We hypothesized that CCR7 also plays a role in CD8(+) T-cell protection
      from apoptosis. Its expression was determined on circulating T cells in patients
      with cancer and related to that of molecules responsible for lymphocyte
      susceptibility/resistance to apoptosis. Peripheral blood mononuclear cells were
      obtained from 36 patients with squamous cell carcinoma of the head and neck and
      16 normal controls. Multicolor flow cytometry was used to evaluate CCR7, Fas,
      Bax, and Bcl-2 expression in CD8(+) T cells. Annexin V binding to CD8(+)CCR7(+)
      and CD8(+)CCR7(-) T-cell subsets was compared. Fewer CD8(+)CCR7(+) T cells bound
      Annexin V than CD8(+)CCR7(-) T cells in normal control and patients (P < 0.0001).
      CCR7 expression correlated with higher Bcl-2 but lower Bax and Fas expression
      levels in CD8(+) T cells in both normal control and patients (P < 0.0001). In
      patients, the CD8(+)CCR7(+) subset was reduced relative to normal control (P =
      0.008) and replaced with an excess of apoptosis-sensitive CD8(+)CCR7(-) T cells.
      To study CCR7 signaling, CD8(+) T cells were stimulated with CCR7 ligands,
      chemokine C ligands 19 or 21. Ligand binding to CCR7 resulted in phosphorylation
      of Akt and increased Bcl-2 expression in CD8(+)CCR7(+) T cells, suggesting that
      CCR7 protects effector T cells from apoptosis through the phosphatidylinositol 3
      kinase/Akt pathway. The absence of CCR7 expression on the majority of CD8(+) T
      cells in the peripheral circulation of patients with squamous cell carcinoma of
      the head and neck contributes to apoptosis and a rapid turnover of these effector
      cells.

PMID- 16278416
TI  - Establishment of a serum tumor marker for preclinical trials of mouse prostate
      cancer models.
AB  - Current prostate cancer research in both basic and preclinical trial studies
      employ genetically engineered mouse models. However, unlike in human prostate
      cancer patients, rodents have no counterpart of prostatic-specific antigen (PSA)
      for monitoring prostate cancer initiation and progression. In this study, we
      established a mouse serum tumor marker from a mouse homologue of human prostate
      secretory protein of 94 amino acids (PSP94). Immunohistochemistry studies on
      different histologic grades from both transgenic and knock-in mouse prostate
      cancer models showed the down-regulation of tissue PSP94 expression (P < 0.001),
      the same as for PSA and PSP94 in humans. The presence of mouse serum PSP94 was
      shown by affinity column and immunoprecipitation purification using a polyclonal
      mouse PSP94 antibody. A competitive ELISA protocol was established to quantify
      serum PSP94 levels with a sensitivity of 1 ng/mL. Quantified serum levels of
      mouse PSP94 ranged from 49.84 ng/mL in wild-type mice to 113.86, 400.45, and
      930.90 ng/mL in mouse prostatic intraepithelial neoplasia with microinvasion,
      well differentiated, moderately differentiated, and poorly differentiated
      prostate cancer genetically engineered prostate cancer mice, respectively (P <
      0.01, n = 68). This increase in serum PSP94 is also well correlated with age and
      tumor weight. Through longitudinal monitoring of serum PSP94 levels of castrated
      mice (androgen ablation therapy), we found a correlation between
      responsiveness/refractory prostate tissues and serum PSP94 levels. The utility of
      mouse serum PSP94 as a marker in hormone therapy was further confirmed by three
      dimensional ultrasound imaging. The establishment of the first rodent prostate
      cancer serum biomarker will greatly facilitate both basic and preclinical
      research on human prostate cancer.

PMID- 16278417
TI  - Radioimmunotherapy of CD22-expressing Daudi tumors in nude mice with a 90Y
      labeled anti-CD22 monoclonal antibody.
AB  - A study was undertaken to investigate the efficacy of a high affinity, rapidly
      internalizing anti-CD22 monoclonal antibody for selectively delivering high
      energy (90)Y radioactivity to B lymphoma cells in vivo. The antibody, RFB4, was
      readily labeled with (90)Y using the highly stable chelate, 1B4M
      diethylenetriaminepentaacetic acid. Labeled RFB4 selectively bound to the CD22(+)
      Burkitt's lymphoma cell line Daudi, but not to CD22(-) control cells in vitro as
      compared with a control antibody, and was more significantly bound (P = 0.03) to
      Daudi solid tumors growing in athymic nude mice. Biodistribution data correlated
      well with the antitumor effect. The therapeutic effect of (90)Y-labeled anti-CD22
      (Y22) was dose-dependent, irreversible, and the best results were achieved in
      mice receiving a single i.p. dose of 196 microCi. These mice displayed a
      significantly better (P < 0.01) antitumor response than control mice and survived
      >200 days with no evidence of tumor. Histology studies showed no significant
      injury to kidney, liver, or small intestine. Importantly, tumor-bearing mice
      treated with Y22 had no radiologic bone marrow damage compared with tumor-bearing
      mice treated with the control-labeled antibody arguing that the presence of
      CD22(+) tumor protected mice from bone marrow damage. When anti-CD22
      radioimmunotherapy was compared to radioimmunotherapy with anti-CD19 and anti
      CD45 antibodies, all three antibodies distributed significantly high levels of
      radioisotope to flank tumors in vivo compared with controls (P < 0.05), induced
      complete remission, and produced long-term, tumor-free survivors. These findings
      indicate that anti-CD22 radioimmunotherapy with Y22 is highly effective in vivo
      against CD22-expressing malignancies and may be a useful therapy for drug
      refractory B cell leukemia patients.

PMID- 16278418
TI  - [131I]meta-iodobenzylguanidine and topotecan combination treatment of tumors
      expressing the noradrenaline transporter.
AB  - PURPOSE: Both [(131)I]meta-iodobenzylguanidine ([(131)I]MIBG) and the
      topoisomerase I inhibitor topotecan are effective as single-agent treatments of
      neuroblastoma. The aim of this study was to investigate the efficacy of
      [(131)I]MIBG in combination with topotecan in vitro and in vivo. EXPERIMENTAL
      DESIGN: The cell lines used were SK-N-BE(2c) (human neuroblastoma) and UVW/NAT
      (glioma cell line transfected with the noradrenaline transporter gene). Three
      different treatment schedules were assessed: topotecan given before (schedule 1),
      after (schedule 2), or simultaneously (schedule 3) with [(131)I]MIBG. DNA strand
      breakage was evaluated by comet assay, and cytotoxicity was determined by
      clonogenic survival. Efficacy was also measured by growth delay of tumor
      xenografts in nude mice. RESULTS: Combination schedules 2 and 3 caused more
      cytotoxicity than schedule 1. Similarly, significant DNA damage was observed
      following treatment schedules 2 and 3 (P < 0.005) but not schedule 1. The mean
      number of days for a doubling in volume of SK-N-BE(2c) tumors and a 10-fold
      increase in volume of UVW/NAT tumors were 10.4 and 18.6 (untreated), 19.7 and
      25.3 (topotecan alone), 22.8 and 31.9 ([(131)I]MIBG alone), 26.3 and 37.1
      (combination schedule 1), 34.3 and 49.7 (combination schedule 2), and 53.2 and
      >71 (combination schedule 3), respectively. The highest rate of cure of both
      xenografts was observed following treatment with combination schedule 3.
      CONCLUSIONS: The combination of topotecan and [(131)I]MIBG compared with either
      treatment alone gave rise to greater than additive DNA damage, clonogenic cell
      kill, and tumor growth delay. These effects were dependent on the scheduling of
      the two agents.

PMID- 16278419
TI  - Novel Phase I dose de-escalation design trial to determine the biological
      modulatory dose of the antiangiogenic agent SU5416.
AB  - PURPOSE: To determine the biological modulatory dose of SU5416, we employed a
      novel trial design, where "dose de-escalation" was based on demonstrable
      biological changes observed at the maximum tolerated dose. If such an effect was
      shown, dose de-escalation to a predefined dose level would occur to determine if
      the lower dose exhibited the same amount of pharmacodynamic effect as the higher
      dose. EXPERIMENTAL DESIGN: Ten patients with advanced solid tumors were enrolled
      at each dose level. One of the following pharmacodynamic effects was considered
      significant: (a) a 35% decrease in microvessel density in sequential tumor
      biopsies and (b) a 35% decrease in blood flow within tumor as assessed by dynamic
      contrast-enhanced magnetic resonance imaging. In addition, soluble E-selectin,
      soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule,
      and plasma vascular endothelial growth factor were measured sequentially.
      RESULTS: Nineteen patients were enrolled. Sequential tumor biopsies in all
      evaluable patients showed an increase in microvessel density. Only one patient
      met the intended pharmacodynamic end point of >35% reduction in blood flow. There
      was a significant increase in both soluble E-selectin and soluble intercellular
      adhesion molecule levels pretreatment versus levels at the time of removal of
      patients from study (P = 0.04 and P = 0.0007, respectively). Levels of serum
      fibrinogen rose with therapy. There was a trend toward increase in plasma
      vascular endothelial growth factor levels. CONCLUSION: SU5416 does not result in
      decreased blood flow in tumors or a decrease in microvessel density. This
      corresponds to the lack of clinical activity seen with this agent. Our clinical
      trial design termed dose de-escalation is a novel approach to determine the in
      vivo biological effects of targeted therapies in cancer patients.

PMID- 16278420
TI  - Histone deacetylase inhibitor FK228 activates tumor suppressor Prdx1 with
      apoptosis induction in esophageal cancer cells.
AB  - PURPOSE: The histone deacetylase inhibitor FK228 shows strong activity as a
      potent antitumor drug but its precise mechanism is still obscure. The purpose of
      this study is to reveal the effect of FK228 on gene expression in the cell and to
      determine the mechanism of the antitumor activity of FK228 for further clinical
      applications. EXPERIMENTAL DESIGN AND RESULTS: Microarray analysis was applied to
      verify the gene expression profiles of 4,608 genes after FK228 treatment using
      human esophageal squamous cell cancer cell lines T.Tn and TE2. Among them,
      peroxiredoxin 1 (Prdx1), a member of the peroxiredoxin family of antioxidant
      enzymes having cell growth suppression activity, as well as p21(WAF1), were
      significantly activated by FK288. In addition, FK228 strongly inhibited the cell
      growth of T.Tn and TE2 by the induction of apoptosis. Further, chromatin
      immunoprecipitation analysis revealed that FK228 induced the accumulation of
      acetylated histones H3 and H4 in Prdx1 promoter, including the Sp1-binding site.
      In mouse xenograft models of T.Tn and TE2 cells, FK228 injection resulted in
      significant tumor regression as well as activated Prdx1 expression in tumor
      tissues. Prdx1 suppression by RNA interference hindered the antitumor effect of
      FK228. CONCLUSION: Our results indicate that the antitumor effect of FK228 in
      esophageal cancer cells is shown at least in part through Prdx1 activation by
      modulating acetylation of histones in the promoter, resulting in tumor growth
      inhibition with apoptosis induction.

PMID- 16278421
TI  - Prevention of hepatocellular carcinoma by universal vaccination against hepatitis
      B virus: the effect and problems.
AB  - PURPOSE: In spite of the success of hepatitis B immunization, still a significant
      proportion of childhood hepatocellular carcinoma (HCC) failed to be prevented by
      the hepatitis B immunization program. This study is aimed to investigate the
      problems in the HCC prevention in children. EXPERIMENTAL DESIGN: All HCC children
      ages 6 to 14 diagnosed between 1981 and 2000 in Taiwan were collected from two
      national childhood HCC registry systems. We analyzed the causes of HCC prevention
      failure and the risk ratio of HCC among hepatitis B carriers born before versus
      after the vaccination program. RESULTS: The incidence of HCC per 100,000 children
      declined from 0.54 to 0.20 in those born before versus after the vaccination
      program (risk ratio, 0.36). Vaccine failure (33.3-51.4%) and failure to receive
      hepatitis B immunoglobulin at birth (42.4-57.5%) were the main causes of HCC
      prevention failure. Mother-to-child transmission of hepatitis B virus infection
      is an important risk factor of HCC development. This is evidenced by the very
      high hepatitis B surface antigen seropositive rate in our HCC children (97%) and
      their mothers (96%). Hepatitis B carrier children born after the vaccination
      program had a higher risk of developing HCC than those born before the program
      (risk ratio, 2.3-4.5). CONCLUSIONS: Vaccine failure and failure to receive
      hepatitis B immunoglobulin are the main problems preventing eradication of HCC.
      Hepatitis B carrier children born after the immunization program have a higher
      risk of developing HCC than those born before.

PMID- 16278422
TI  - Independent test set performance in the prediction of early relapse in ovarian
      cancer with gene expression profiles.

PMID- 16278423
TI  - Intrabacterial proton-dependent CagA transport system in Helicobacter pylori.
AB  - Helicobacter pylori CagA modifies the signalling of host cells and causes gastric
      diseases. Although CagA is injected into gastric epithelial cells through the
      type IV secretion machinery, it remains unclear how CagA is transported towards
      the machinery in the bacterial cytoplasm. In this study, it was determined that
      the proton-dependent intracytoplasmic transport system correlates with the
      priming of CagA secretion from H. pylori. The cytotoxicity of neutral-pH- and
      acidic-pH-treated H. pylori was examined in the AGS cell line. The amount of
      phosphorylated CagA in AGS cells incubated with acidic-pH- and neutral-pH-treated
      H. pylori was determined by enzyme immunoassay and Western blot. The production
      of CagA and adherence of the treated bacteria were examined by enzyme immunoassay
      and light microscopy, respectively. To clarify how CagA is transported towards
      the inner membrane of the treated bacteria, the localization of CagA was analysed
      by immunoelectron microscopy. The proportion of hummingbird cells in the AGS cell
      line rapidly increased following the inoculation of acidic-pH-treated H. pylori
      but increased more slowly with neutral-pH-treated H. pylori, and the phenomenon
      correlated with the amount of phosphorylated CagA in AGS cells. CagA was densely
      localized near the inner membrane in the acidic-pH-treated bacterial cytoplasm,
      but this localization was not observed in the neutral-pH-treated bacterial
      cytoplasm, suggesting that CagA shifts from the centre to the peripheral portion
      of the cytoplasm as a result of an extracellular decrease in pH. This phenomenon
      depended on the presence of UreI, a proton-dependent urea channel, but not on the
      presence of urea. The pH treatments did not enhance CagA production or the
      adherence of the bacterium to AGS cells. The authors propose that H. pylori
      possesses a proton-dependent intracytoplasmic transport system that probably
      accelerates priming for CagA injection.

PMID- 16278424
TI  - Microarray-based pncA genotyping of pyrazinamide-resistant strains of
      Mycobacterium tuberculosis.
AB  - Drug-resistant Mycobacterium tuberculosis poses a significant threat to the
      treatment of tuberculosis (TB). The current susceptibility testing for the first
      line TB drug pyrazinamide (PZA) is not only time-consuming but also difficult,
      due to the requirement for acid pH for drug activity. Predominantly, resistance
      to PZA in M. tuberculosis is caused by mutations in the pncA gene, and the
      detection of pncA mutations can be an indicator of PZA resistance. In this study,
      the use of a previously developed microarray method for the rapid detection of
      PZA-resistant M. tuberculosis based on identifying mutations in the pncA gene was
      evaluated. Microarray analysis was performed in a blind manner on 33 clinical
      isolates of M. tuberculosis for which the sequence of the pncA gene had not
      previously been determined. The results showed that all mutations in PZA
      resistant strains identified by DNA sequencing could be unambiguously detected by
      the microarray method. It is concluded that the microarray method is a valuable
      tool for the rapid screening and genetic identification of potential PZA
      resistant M. tuberculosis strains.

PMID- 16278425
TI  - Simultaneous detection and serotype identification of Streptococcus agalactiae
      using multiplex PCR and reverse line blot hybridization.
AB  - Streptococcus agalactiae (group B streptococcus, GBS) is an important cause of
      sepsis in neonates and their mothers, and the elderly and immunocompromised
      patients. Ongoing surveillance to monitor GBS serotype distribution is needed to
      guide the development and assess the feasibility of GBS conjugate vaccines. The
      authors previously developed a molecular serotype identification method based on
      serotype-specific PCR and partial sequencing of cps genes. In this study, a novel
      10-primer pair multiplex PCR and reverse line blot (mPCR/RLB) hybridization assay
      was developed for simultaneous detection and serotype identification of all nine
      GBS serotypes. For all 316 GBS isolates tested the mPCR/RLB results corresponded
      with those of conventional serotyping and individual serotype-specific PCR, and
      the method was more convenient and practical than either alternative.

PMID- 16278426
TI  - Audit of the laboratory diagnosis of Lyme disease in Scotland.
AB  - An audit was performed on the laboratory diagnosis of lyme disease in Scotland.
      The problem of a significant number of patients with clinical symptoms of lyme
      disease being reported as seronegative or equivocal by the confirmatory Western
      blot test was identified. Comparisons of current practice were made with American
      and European standards, and the Western blot scoring system revised. When applied
      retrospectively (April 2003 to March 2004), 39 (33 %) of 116 serum samples
      previously negative or equivocal became weak positive or stronger. Thirty-one (80
      %) of these 39 samples were from patients with clinical details suggestive of
      early lyme disease. The changes were implemented and assessed prospectively for 6
      months. There was a significant increase in the proportion of equivocal results,
      with fewer negatives compared to the same time period 1 year previously. This
      audit has helped clinicians in the diagnosis of lyme disease and the management
      of these patients in Scotland.

PMID- 16278427
TI  - Chlamydia pneumoniae growth inhibition in human monocytic THP-1 cells and human
      epithelial HEp-2 cells by a novel phenoxazine derivative.
AB  - In this study the effects of 2-amino-phenoxazine-3-one (phenoxazine derivate, Phx
      3) on Chlamydia (Chlamydophila) pneumoniae growth in human monocytic THP-1 cells
      as well as human epithelial HEp-2 cells were examined. Cells were infected with
      bacteria at an m.o.i. of 10 by centrifugation. After washing to remove any
      remaining bacteria, the cells were incubated with or without Phx-3 in the
      presence or absence of tryptophan for 72 h. The bacteria in cells were assessed
      by staining of chlamydial inclusions with FITC-labelled anti-chlamydial antibody,
      electron microscopic analysis, real-time RT-PCR specific for C. pneumoniae 16S
      rRNA and propagation on HEp-2 cells. Treatment with Phx-3 significantly inhibited
      growth of C. pneumoniae in THP-1 and HEp-2 cells. A decrease in the number of
      bacterial 16S rRNA transcripts was also confirmed in both cell lines by real-time
      RT-PCR. Electron microscopic studies revealed that treatment with Phx-3 induces
      bacterial destruction in most of the inclusion bodies in these cells. Addition of
      tryptophan to the culture slightly blocked the growth inhibition of C. pneumoniae
      by Phx-3. The reagents did not show any cytotoxicity to the cells at the
      concentrations used. The results suggest that Phx-3 inhibits C. pneumoniae
      replication in human monocytic cells as well as epithelial cells, partially
      depending on the tryptophan-metabolic pathway of host cells. Thus, Phx-3 might be
      a useful compound for controlling C. pneumoniae growth in cells and may be an
      alternative conventional therapy.

PMID- 16278428
TI  - Detection and characterization of tet(M) in tetracycline-resistant Listeria
      strains from human and food-processing origins in Belgium and France.
AB  - In the present study, three Listeria monocytogenes strains and one Listeria
      innocua strain out of a collection of 241 Listeria isolates from human and food
      processing sources were found to display resistance to tetracycline (TC) due to
      the presence of the tet(M) gene. Through sequence analysis, it was shown that
      tet(M) genes in two of the isolates belong to sequence homology group (SHG) II, a
      group comprising chromosomally encoded tet(M) genes previously found in
      Staphylococcus aureus and in lactobacilli. The tet(M) genes of the two other L.
      monocytogenes strains were associated with a member of the Tn916-Tn1545 family of
      conjugative transposons and were closely related to SHG III, which harbours
      enterococcal tet(M) genes associated with Tn916. One of these transposon
      containing strains was able to transfer the tet(M) gene to Enterococcus faecalis
      recipient strain JH2-2. Collectively, these sequence and conjugation data
      indicate that the acquisition of tet(M) by Listeria strains may be triggered by
      successive transfers between other Gram-positive organisms.

PMID- 16278429
TI  - Comparison of clarithromycin and ciprofloxacin therapy for Bacillus anthracis
      Sterne infection in mice with or without (60)Co gamma-photon irradiation.
AB  - Biological agents and ionizing radiation lead to more severe clinical outcomes
      than either insult alone. This study investigated the survival of non-irradiated
      and (60)Co-gamma-irradiated mice given therapy for inhalation anthrax with
      ciprofloxacin (CIP) or a clinically relevant mixture of clarithromycin (CLR) and
      its major human microbiologically important metabolite 14-hydroxy clarithromycin
      (14-OH CLR). All B6D2F1/J 10-week-old female mice were inoculated intratracheally
      with 3 x 10(8) c.f.u. of Bacillus anthracis Sterne spores 4 days after the non
      lethal 7 Gy dose of (60)Co gamma radiation. Twenty-one days of treatment with
      CLR/14-OH CLR, 150 mg kg(-1) twice daily, or CIP, 16.5 mg kg(-1) twice daily,
      began 24 h after inoculation. Pharmacokinetics indicate that the area under the
      curve (AUC) for 14-OH CLR on the concentration-versus-time graph was slightly
      higher in gamma-irradiated than non-irradiated animals. Neither drug was able to
      increase survival in gamma-irradiated animals. CIP and CLR/14-OH CLR therapies in
      non-irradiated animals increased survival from 49 % (17/35 mice) in buffer
      treated animals to 94 % (33/35) and 100 %, respectively (P < 0.001). B. anthracis
      Sterne only was isolated from 25-50 % of treated mice with or without
      irradiation. Mixed infections with B. anthracis Sterne were present in 50-71 % of
      gamma-irradiated mice but only in 5-10 % of mice without irradiation.

PMID- 16278430
TI  - Laboratory-based surveillance of human verocytotoxigenic Escherichia coli
      infection in the Republic of Ireland, 2002-2004.
AB  - The aim of this study was to examine the frequency and distribution of human
      verocytotoxigenic Escherichia coli (VTEC) O157 and non-O157 in the Republic of
      Ireland, and also to examine the presence of virulence genes in these isolates.
      This genetic information combined with phenotypic tests was used to produce a
      complete laboratory-based surveillance of human clinical VTEC infection in the
      Republic of Ireland between 2002 and 2004. Between January 2002 and December 2004
      a total of 207 VTEC isolates were studied (one isolate per patient), 185 (89 %)
      of these were E. coli O157. The remaining 22 (11 %) were non-O157 E. coli, made
      up of 15 (7.2 %) E. coli O26, one (0.5 %) E. coli O103, one (0.5 %) E. coli O146,
      one (0.5 %) E. coli O145, two (1 %) E. coli O111 and two (1 %) ungroupable VTEC.
      These isolates originated from the eight health boards in the Republic of Ireland
      and represented over 90 % of the clinical cases of VTEC in the Republic of
      Ireland during this period. The results showed that VTEC O157 was the predominant
      serogroup and had a predominant toxin genotype of VT2 alone. Phage type 32 was
      the most common phage type of E. coli O157 identified. Non-O157 VTEC was a small
      proportion of all VTEC (10 % in 2002, 8 % in 2003, 15.5 % in 2004). In 2004 it
      was noted that there was an increase in the number and variety of non-O157 VTEC
      strains; however, this requires further monitoring in the future to see if this
      trend is sustained. It was also noted throughout the study period that the
      incidence of VTEC was higher in rural areas. Implementation of real-time PCR for
      the detection and subtyping of VTEC has aided outbreak investigations and is
      important for enhanced surveillance of VTEC in the Republic of Ireland.

PMID- 16278432
TI  - Rapid and simple detection of blaCTX-M genes by multiplex PCR assay.
AB  - A novel multiplex PCR assay is described (CTX-Mplex PCR) that allows rapid
      detection of bla(CTX-M) genes and discrimination between groups 1, 2, 9 and
      25/26. The specificity and sensitivity of the assay were evaluated with 10
      control strains and then applied to 62 clinical isolates. The multiplex PCR
      detected and classified bla(CTX-M) genes with 100 % accuracy. The utilization of
      a denaturing HPLC WAVE system to size the PCR products automatically from the
      multiplex PCR enhances the assay by saving time and costs.

PMID- 16278431
TI  - Expression of cellulose and curli fimbriae by Escherichia coli isolated from the
      gastrointestinal tract.
AB  - Escherichia coli colonizes the gastrointestinal tract of humans; however, little
      is known about the features of commensal strains. This study investigated whether
      expression of the biofilm extracellular matrix components cellulose and curli
      fimbriae is found among commensal isolates. Fifty-two E. coli strains were
      isolated from faecal samples and, as a control, 24 strains from urinary tract
      infections were also used. Faecal isolates were characterized by serotyping and
      phylogenetically grouped by PCR. The genotype was determined by PFGE and the
      presence of virulence factors was assessed. Co-expression of cellulose and curli
      fimbriae at 28 degrees C and 37 degrees C was typical for faecal isolates, while
      urinary tract infection strains typically expressed the extracellular matrix
      components at 28 degrees C only. Knockout studies in a representative faecal
      isolate revealed that the response regulator CsgD regulated cellulose and curli
      fimbriae, as found previously in Salmonella enterica. In contrast to S. enterica,
      at 37 degrees C pellicle formation occurred in the absence of cellulose and curli
      fimbriae. The gastrointestinal tract represents a source of biofilm-forming
      bacteria, which can spread to susceptible sites.

PMID- 16278433
TI  - Mutational and expression analysis of tbnat and its response to isoniazid.
AB  - A gene (nat) encoding arylamine N-acetyltransferase (NAT) has been found in
      Mycobacterium tuberculosis. The gene is expressed and the enzyme is active in
      growing M. tuberculosis cells. N-Acetyltransferase acetylates and inactivates
      isoniazid (INH), which is a front-line drug used in tuberculosis (TB) therapy. In
      this study, it was shown that a previously reported G619A single nucleotide
      polymorphism (SNP) was conserved in two M. tuberculosis strain families found in
      the Western Cape Province of South Africa (strain families 3 and 28). Further
      sequence analysis of isolates in strain family 3 identified a new T529C SNP in
      NAT resulting in a histidine instead of a tyrosine at position 177. This SNP was
      found only in isolates from strain family 3, and this mutation affects the highly
      conserved tyrosine residue close to the active site. Using real-time PCR, the
      expression of M. tuberculosis nat (tbnat) was determined over a 28 day growth
      cycle of the M. tuberculosis reference strain (H37Rv). The expression of tbnat
      occurs early in growth and reaches maximum levels at mid-exponential phase. The
      exposure of INH-susceptible isolates to low levels of INH resulted in an increase
      of tbnat expression (reference strain H37Rv, which is wild-type for tbnat, and
      isolate 1430, containing both SNPs). An INH-resistant isolate (816) exposed to
      INH showed no change in tbnat expression. The increased expression in the
      susceptible isolates suggests that INH affects tbnat expression. tbnat may
      contribute to INH susceptibility, but in combination with other factors.

PMID- 16278434
TI  - Biofilm formation on intrauterine devices in relation to duration of use.
AB  - Intrauterine devices (IUDs) are highly effective, long-term methods of
      contraception; however, IUD use is limited due to concerns about an increased
      risk of pelvic inflammatory disease (PID) and subsequent complications. A
      retrospective review of clinical and microbiological data of 127 participants was
      carried out over a 3 year period. IUDs were removed and sent for microbiological
      examination. A 10 year old IUD, removed because of the symptoms of PID, was
      investigated via both microbial culture and scanning electron microscopy. The
      primary objective of this study was to examine the bacteria present on removed
      IUDs after different times in situ by using aerobic and anaerobic culture
      methods. A close association of the distribution of aerobic and anaerobic
      bacteria on the IUDs with different times in situ was found.

PMID- 16278436
TI  - Comparison of three Legionella urinary antigen assays during an outbreak of
      legionellosis in Belgium.
AB  - During an outbreak of legionellosis in Belgium, urine samples of 32 legionellosis
      patients were tested with three Legionella urinary antigen assays: the Biotest
      enzyme immunoassay (EIA) kit, the Binax EIA kit and the Binax NOW
      Immunochromatographic Test kit. The three tests were concomitantly compared. The
      test sensitivities on the first urine samples were 65.6 % for the Biotest EIA,
      50.0 % for the Binax EIA and 56.3 % for the Binax NOW. Testing of a second urine
      sample increased the sensitivities to 71.9 %, 59.4 % and 65.6 %, respectively.
      The differences were not statistically significant. In outbreak settings, testing
      second samples from patients presenting with symptoms but initially testing
      negative and/or concentrating urine samples for testing might be valuable
      additions to the urinary antigen test to increase the sensitivities of the tests.

PMID- 16278435
TI  - New approaches to identification of bacterial pathogens by surface enhanced laser
      desorption/ionization time of flight mass spectrometry in concert with artificial
      neural networks, with special reference to Neisseria gonorrhoeae.
AB  - Surface enhanced laser desorption/ionization-time of flight mass spectrometry
      (SELDI-TOF MS) has been applied in large numbers of oncological studies but the
      microbiological field has not been extensively explored to date. This paper
      describes the application of SELDI-TOF MS in concert with a multi-layer
      perceptron artificial neural network (ANN) with a back propagation algorithm for
      the identification of Neisseria gonorrhoeae. N. gonorrhoeae, the aetiological
      agent of gonorrhoea, is the second most common sexually transmitted disease in
      the UK and USA. Analysis of over 350 strains of N. gonorrhoeae and closely
      related species by SELDI-TOF MS facilitated the design of an ANN model and
      revealed 20 ion peak descriptors of positive, negative and secondary nature that
      were paramount for the identification of the pathogen. The model performed with
      over 96 % efficiency when based on these 20 ion peak descriptors and exhibited a
      sensitivity of 95.7 % and a specificity of 97.1 %, with an area under the curve
      value of 0.996. The technology has the potential to link several ANN models for a
      comprehensive rapid identification platform for clinically important pathogens.

PMID- 16278437
TI  - Amplified fragment length polymorphism based identification of genetic markers
      and novel PCR assay for differentiation of Campylobacter fetus subspecies.
AB  - Differentiation of Campylobacter fetus into C. fetus subsp. fetus (Cff) and C.
      fetus subsp. venerealis (Cfv) is important for both clinical and economic
      reasons. In the past, several molecular typing methods have been used for
      differentiation, including amplified fragment length polymorphism (AFLP). In this
      study, AFLP was employed to identify C. fetus subspecies specific markers that
      can serve as a basis for design of novel PCR primer sets for Cfv. Four groups of
      C. fetus strains with different phenotypic or genotypic traits were examined by
      AFLP using 22 different DdeI/MboI primer combinations. Specific AFLP fragments
      were deduced and sequenced resulting in 41 sequences. Based on the obtained
      sequences, five potential subspecies-specific PCR assays were developed.
      Extensive evaluation of the five selected PCRs with a set of 65 diverse C. fetus
      strains identified primer set Cf C05 as subspecies Cfv-specific. This newly
      developed PCR is fully consistent with the AFLP subspecies differentiation
      results. The data indicate AFLP as a powerful tool for comparing closely related
      genomes and for exploiting this information to develop a specific PCR with
      extensive typing potential.

PMID- 16278438
TI  - Effect of visible light on malodour production by mixed oral microflora.
AB  - Oral malodour is considered to be caused by the proteolytic activity of anaerobic
      Gram-negative oral bacteria. In a previous study, it was shown that these
      bacteria were susceptible to blue light (wavelengths of 400-500 nm). In this
      study, the effect of blue light on malodour production by mixed oral microflora
      was tested in a salivary incubation assay. Whole saliva samples were exposed to a
      xenon light source for 30, 60, 120 and 240 s, equivalent to fluences of 34, 68,
      137 and 274 J cm(-2), respectively. Malodour was scored by two judges. The levels
      of volatile sulfide compounds (VSC) were measured using a sulfide monitor
      (Halimeter), the microbial population was assessed using viable counts and
      microscopy, salivary protein degradation was followed by SDS-PAGE densitometry
      and VSC-producing bacteria were demonstrated using a differential agar. The
      results showed that the exposure of mixed salivary microflora to blue light
      caused a reduction in malodour production concomitant with a selective inhibitory
      effect on the population of Gram-negative oral bacteria. These results suggest
      that light exposure might have clinical applications for the treatment of oral
      malodour.

PMID- 16278439
TI  - Detection of potentially novel bacterial components of the human skin microbiota
      using culture-independent molecular profiling.
AB  - Although the micro-organisms forming the cutaneous microbiota are considered to
      play important roles in the modification and prevention of skin diseases, a
      comprehensive analysis of their composition has not yet been carried out because
      of difficulties in determining yet-to-be-cultured micro-organisms in the samples.
      Swab-scrubbed forehead skin samples of five healthy volunteers were analysed by
      profiling 16S rRNA genes, as well as by conventional culture methods, to provide
      a profile of the cutaneous microbiota that included yet-to-be-cultured bacteria
      from normal human skin. Cluster analyses of the 16S rRNA gene sequences indicated
      a marked increase in diversity compared with that derived from the culture
      methods. Nineteen previously recognized species and 13 novel phylotypes were
      obtained from the analysis of 416 clones. In addition to well-known bacteria such
      as Staphylococcus epidermidis and Propionibacterium acnes, phylotype A, the 16S
      rRNA gene of which is 97 % similar to that of Methylophilus methylotrophus, was
      detected in three of the five samples, in one of which it was the predominant
      clone. Culture-independent genetic profiling of 16S rRNA genes for detecting
      human cutaneous microbiota has allowed us to detect potentially novel components
      of the cutaneous microbiota in humans.

PMID- 16278440
TI  - Investigations into the influence of host genetics on the predominant eubacteria
      in the faecal microflora of children.
AB  - The eubacterial population was studied in faecal samples of related and unrelated
      children. Temporal temperature gradient gel electrophoresis (TTGE) provided a
      snapshot of the bacterial population and allowed calculation of the degree of
      similarity in the predominant faecal microflora of identical twin pairs,
      fraternal twin pairs and unrelated paired controls. The highest levels of
      similarity were found in genetically identical twins. Significant differences
      were observed between the identical and fraternal twins (P = 0.037), strongly
      suggesting a genetic influence over the composition of the faecal microflora. The
      unrelated control group had the lowest similarity and was significantly different
      from the twins (P = 0.001). The results of this study indicate that host genetics
      influence the composition of the dominant eubacterial population in children.

PMID- 16278441
TI  - Outbreak of Chlamydophila pneumoniae infection in long-term care facilities and
      an affiliated hospital.
AB  - This paper reports an outbreak of Chlamydophila pneumoniae infection in long-term
      care facilities and an affiliated hospital. The outbreak involved rapid spread of
      infection, and was inconsistent with several outbreaks experienced among younger
      populations. In addition, there were differences in the incidences among
      facilities and the affiliated hospital in relation to mean age. Our findings
      indicate that it is possible that elderly residents may be more susceptible to
      acquiring this infection. Physicians and other health care providers in long-term
      care facilities should consider C. pneumoniae in the differential diagnosis of an
      outbreak of respiratory infection.

PMID- 16278442
TI  - Severe endometritis caused by genital mycoplasmas after Caesarean section.
AB  - Infrequently, post-Caesarean endometritis can progress to severe conditions. A
      case of post-Caesarean endometritis caused by Mycoplasma hominis and Ureaplasma
      urealyticum is reported in a young patient. In therapy-resistant endometritis
      unusual causative organisms should be considered and special microbiological
      investigations are recommended.

PMID- 16278443
TI  - Accelerated cell death in Podospora autophagy mutants.
AB  - Although autophagy is characteristic of type II programmed cell death (PCD), its
      role in cell death is currently debated. Both cell death-promoting and
      prosurvival roles of autophagy have been reported depending on the organism and
      the cell type. In filamentous fungi, a cell death reaction known as an
      incompatibility reaction occurs when cells of unlike genotype fuse. Cell death by
      incompatibility is characterized by a dramatic vacuolar enlargement and cell
      lysis. In Podospora anserina, autophagy is induced early during this cell death
      reaction. Cell death by incompatibility in Podospora is a model of type II PCD
      used here to assess the role of autophagy in this type of cell death. We have
      inactivated PaATG1, the Podospora ortholog of the Saccharomyces cerevisiae ATG1
      gene involved in the early steps of autophagy in yeast. The DeltaPaATG1 mutant
      displays developmental defects characteristic of abrogated autophagy in
      Podospora. Using the green fluorescent protein-PaATG8 autophagosome marker, we
      show that autophagy is abolished in this mutant. Neither cell death by
      incompatibility nor vacuolization are suppressed in DeltaPaATG1 and DeltaPaATG8
      autophagy mutants, indicating that a vacuolar cell death reaction without
      autophagy occurs in Podospora. Our results thus provide a novel example of a type
      II PCD reaction in which autophagy is not the cause of cell death. In addition,
      we found that cell death is accelerated in DeltaPaATG null mutants, suggesting
      that autophagy has a protective role in this type II PCD reaction.

PMID- 16278444
TI  - Involvement of a short interspersed element in epigenetic transcriptional
      silencing of the amoebapore gene in Entamoeba histolytica.
AB  - Transcriptional silencing of an amoebapore (ap-a) gene occurred in Entamoeba
      histolytica following the transfection of plasmids containing a DNA segment (473
      bp) homologous to the 5' upstream region of the gene (R. Bracha, Y. Nuchamowitz,
      and D. Mirelman, Eukaryot. Cell 2:295-305, 2003). This segment contains the
      promoter region of the ap-a gene, a T-rich stretch, followed by a truncated SINE1
      (short interspersed element 1) that is transcribed from the antisense strand.
      Transfection of plasmids containing truncated SINE1 sequences which lack their 3'
      regulatory elements upstream of the ap-a gene was essential for the downstream
      silencing of the ap-a gene while transfection with plasmids containing the entire
      SINE1 sequence or without the T-rich stretch promoted the overexpression of the
      ap-a gene. Both the T-rich stretch and sequences of the 5' SINE1 were essential
      for the transcription of SINE1. RNA extracts from gene-silenced cultures showed
      small amounts of short (approximately 140-nucleotide), single-stranded molecules
      with homology to SINE1 but no short interfering RNA. Chromatin
      immunoprecipitation analysis with an antibody against methylated K4 of histone H3
      showed a demethylation of K4 at the domain of the ap-a gene, indicating
      transcriptional inactivation. These results suggest the involvement of SINE1 in
      triggering the gene silencing and the role of histone modification in its
      epigenetic maintenance.

PMID- 16278445
TI  - Stress-activated protein kinase pathway functions to support protein synthesis
      and translational adaptation in response to environmental stress in fission
      yeast.
AB  - The stress-activated protein kinase (SAPK) pathway plays a central role in
      coordinating gene expression in response to diverse environmental stress stimuli.
      We examined the role of this pathway in the translational response to stress in
      Schizosaccharomyces pombe. Exposing wild-type cells to osmotic stress (KCl)
      resulted in a rapid but transient reduction in protein synthesis. Protein
      synthesis was further reduced in mutants disrupting the SAPK pathway, including
      the mitogen-activated protein kinase Wis1 or the mitogen-activated protein kinase
      Spc1/Sty1, suggesting a role for these stress response factors in this
      translational control. Further polysome analyses revealed a role for Spc1 in
      supporting translation initiation during osmotic stress, and additionally in
      facilitating translational adaptation. Exposure to oxidative stress (H2O2)
      resulted in a striking reduction in translation initiation in wild-type cells,
      which was further reduced in spc1- cells. Reduced translation initiation
      correlated with phosphorylation of the alpha subunit of eukaryotic initiation
      factor 2 (eIF2alpha) in wild-type cells. Disruption of Wis1 or Spc1 kinase or the
      downstream bZip transcription factors Atf1 and Pap1 resulted in a marked increase
      in eIF2alpha phosphorylation which was dependent on the eIF2alpha kinases Hri2
      and Gcn2. These findings suggest a role for the SAPK pathway in supporting
      translation initiation and facilitating adaptation to environmental stress in
      part through reducing eIF2alpha phosphorylation in fission yeast.

PMID- 16278446
TI  - Cyclic AMP-independent regulation of protein kinase A substrate phosphorylation
      by Kelch repeat proteins.
AB  - Pseudohyphal and invasive growth in the yeast Saccharomyces cerevisiae is
      regulated by the kelch repeat-containing proteins Gpb1p and Gpb2p, which act
      downstream of the G protein alpha-subunit Gpa2p. Here we show that deletion of
      GPB1 and GPB2 causes increased haploid invasive growth in cells containing any
      one of the three protein kinase A (PKA) catalytic subunits, suggesting that Gpb1p
      and Gpb2p are able to inhibit each of these kinases. Cells containing gpb1Delta
      gpb2Delta mutations also display increased phosphorylation of the PKA substrates
      Sfl1p and Msn2p, indicating that Gpb1p and Gpb2p are negative regulators of PKA
      substrate phosphorylation. Stimulation of PKA-dependent signaling by gpb1Delta
      gpb2Delta mutations occurs in cells that lack both adenylyl cyclase and the high
      affinity cyclic AMP (cAMP) phosphodiesterase. This effect is also seen in cells
      that lack the low-affinity cAMP phosphodiesterase. Given that these three enzymes
      control the synthesis and degradation of cAMP, these results indicate that the
      effect of Gpb1p and Gpb2p on PKA substrate phosphorylation does not occur by
      regulating the intracellular cAMP concentration. These findings suggest that
      Gpb1p and Gpb2p mediate their effects on the cAMP/PKA signaling pathway either by
      inhibiting the activity of PKA in a cAMP-independent manner or by activating
      phosphatases that act on PKA substrates.

PMID- 16278447
TI  - Gpi19, the Saccharomyces cerevisiae homologue of mammalian PIG-P, is a subunit of
      the initial enzyme for glycosylphosphatidylinositol anchor biosynthesis.
AB  - Glycosylphosphatidylinositols (GPIs) are attached to the C termini of some
      glycosylated secretory proteins, serving as membrane anchors for many of those on
      the cell surface. Biosynthesis of GPIs is initiated by the transfer of N
      acetylglucosamine (GlcNAc) from UDP-GlcNAc to phosphatidylinositol. This reaction
      is carried out at the endoplasmic reticulum (ER) by an enzyme complex called GPI
      N-acetylglucosaminyltransferase (GPI-GlcNAc transferase). The human enzyme has
      six known subunits, at least four of which, GPI1, PIG-A, PIG-C, and PIG-H, have
      functional homologs in the budding yeast Saccharomyces cerevisiae. The
      uncharacterized yeast gene YDR437w encodes a protein with some sequence
      similarity to human PIG-P, a fifth subunit of the GPI-GlcNAc transferase. Here we
      show that Ydr437w is a small but essential subunit of the yeast GPI-GlcNAc
      transferase, and we designate its gene GPI19. Similar to other mutants in the
      yeast enzyme, temperature-sensitive gpi19 mutants display cell wall defects and
      hyperactive Ras phenotypes. The Gpi19 protein associates with the yeast GPI
      GlcNAc transferase in vivo, as judged by coimmuneprecipitation with the Gpi2
      subunit. Moreover, conditional gpi19 mutants are defective for GPI-GlcNAc
      transferase activity in vitro. Finally, we present evidence for the topology of
      Gpi19 within the ER membrane.

PMID- 16278449
TI  - Group III histidine kinase is a positive regulator of Hog1-type mitogen-activated
      protein kinase in filamentous fungi.
AB  - We previously reported that the group III histidine kinase Dic1p in the maize
      pathogen Cochliobolus heterostrophus is involved in resistance to dicarboximide
      and phenylpyrrole fungicides and in osmotic adaptation. In addition, exposure to
      the phenylpyrrole fungicide fludioxonil led to improper activation of Hog1-type
      mitogen-activated protein kinases (MAPKs) in some phytopathogenic fungi,
      including C. heterostrophus. Here we report, for the first time, the relationship
      between the group III histidine kinase and Hog1-related MAPK: group III histidine
      kinase is a positive regulator of Hog1-related MAPK in filamentous fungi. The
      phosphorylation pattern of C. heterostrophus BmHog1p (Hog1-type MAPK) was
      analyzed in wild-type and dic1-deficient strains by Western blotting. In the wild
      type strain, phosphorylated BmHog1p was detected after exposure to both iprodione
      and fludioxonil at a concentration of 1 microg/ml. In the dic1-deficient strains,
      phosphorylated BmHog1p was not detected after exposure to 10 microg/ml of the
      fungicides. In response to osmotic stress (0.4 M KCl), a trace of phosphorylated
      BmHog1p was found in the dic1-deficient strains, whereas the band representing
      active BmHog1p was clearly detected in the wild-type strain. Similar results were
      obtained for Neurospora crassa Os-2p MAPK phosphorylation in the mutant of the
      group III histidine kinase gene os-1. These results indicate that group III
      histidine kinase positively regulates the activation of Hog1-type MAPKs in
      filamentous fungi. Notably, the Hog1-type MAPKs were activated at high fungicide
      (100 microg/ml) and osmotic stress (0.8 M KCl) levels in the histidine kinase
      mutants of both fungi, suggesting that another signaling pathway activates Hog1
      type MAPKs in these conditions.

PMID- 16278448
TI  - N-terminal arm of Mcm1 is required for transcription of a subset of genes
      involved in maintenance of the cell wall.
AB  - The yeast Mcm1 protein is a member of the MADS box family of transcription
      factors that interacts with several cofactors to differentially regulate genes
      involved in cell-type determination, mating, cell cycle control and arginine
      metabolism. Residues 18 to 96 of the protein, which form the core DNA-binding
      domain of Mcm1, are sufficient to carry out many Mcm1-dependent functions.
      However, deletion of residues 2 to 17, which form the nonessential N-terminal
      (NT) arm, confers a salt-sensitive phenotype, suggesting that the NT arm is
      required for the activation of salt response genes. We used a strategy that
      combined information from the mutational analysis of the Mcm1-binding site with
      microarray expression data under salt stress conditions to identify a new subset
      of Mcm1-regulated genes. Northern blot analysis showed that the transcript levels
      of several genes encoding associated with the cell wall, especially YGP1,
      decrease significantly upon deletion of the Mcm1 NT arm. Deletion of the Mcm1 NT
      arm results in a calcofluor white-sensitive phenotype, which is often associated
      with defects in transcription of cell wall genes. In addition, the deletion makes
      cells sensitive to CaCl2 and alkaline pH. We found that the defect caused by
      removal of the NT arm is not due to changes in Mcm1 protein level, stability, DNA
      binding affinity, or DNA bending. This suggests that residues 2 to 17 of Mcm1 may
      be involved in recruiting a cofactor to the promoters of these genes to activate
      transcription.

PMID- 16278450
TI  - Assembly of the Hap2p/Hap3p/Hap4p/Hap5p-DNA complex in Saccharomyces cerevisiae.
AB  - The CCAAT-binding factor (CBF) is an evolutionarily conserved multimeric
      transcriptional activator in eukaryotes. In Saccharomyces cerevisiae, the CCAAT
      binding factor is composed of four subunits, termed Hap2p, Hap3p, Hap4p, and
      Hap5p. The Hap2p/Hap3p/Hap5p heterotrimer is the DNA-binding component of the
      complex that binds to the consensus 5'-CCAAT-3' sequence in the promoter of
      target genes. The Hap4p subunit contains the transcriptional activation domain
      necessary for stimulating transcription after interacting with Hap2p/Hap3p/Hap5p.
      In this report, we demonstrate that Hap2p, Hap3p, and Hap5p assemble via a one
      step pathway requiring all three subunits simultaneously, as opposed to the
      mammalian CCAAT-binding factor which has been shown to assemble via a two-step
      pathway with CBF-A (Hap3p homolog) and CBF-C (Hap5p homolog) forming a stable
      dimer before CBF-B (Hap2p homolog) can interact. We have also found that the
      interaction of Hap4p with Hap2p/Hap3p/Hap5p requires DNA binding as a
      prerequisite. To further understand the protein-protein and protein-DNA
      interactions of this transcription factor, we identified the minimal domain of
      Hap4p necessary for interaction with the Hap2p/Hap3p/Hap5p-DNA complex, and we
      demonstrate that this domain is sufficient to complement the respiratory
      deficiency of a hap4Delta mutant and activate transcription when fused with the
      VP16 activation domain. These studies provide a further understanding of the
      assembly of the yeast CCAAT-binding factor at target promoters and raise a number
      of questions concerning the protein-protein and protein-DNA interactions of this
      multisubunit transcription factor.

PMID- 16278451
TI  - Activation of AP-1-dependent transcription by a truncated translation initiation
      factor.
AB  - Int6/eIF3e is a highly conserved subunit of eukaryotic translation initiation
      factor 3 (eIF3) that has also been reported to interact with subunits of the
      proteasome and the COP9 signalosome. Overexpression of full-length Int6 or a 13
      kDa C-terminal fragment, Int6CT, in the fission yeast Schizosaccharomyces pombe
      causes multidrug resistance that requires the otherwise inessential AP-1
      transcription factor Pap1. Here we show for the first time that Int6CT acts to
      increase the transcriptional activity of Pap1. Microarray hybridization data
      indicate that Int6CT overexpression resulted in the up-regulation of 67 genes;
      this expression profile closely matched that of cells overexpressing Pap1.
      Analysis of the upstream regulatory sequences of these genes showed that the
      majority contained AP-1 consensus binding sites. Partial defects in ubiquitin
      dependent proteolysis have been suggested to confer Pap1-dependent multidrug
      resistance, but no such defect was seen on Int6CT overexpression. Indeed, none of
      the previously identified interactions of endogenous Int6 was required for the
      activation of Pap1 transcription described here. Moreover, Int6CT-induced
      activation of Pap1-responsive gene expression was independent of the ability of
      Pap1 to undergo a redox-regulated conformational change which mediates its
      relocalization to the nucleus and expression of oxidative stress response genes.
      Int6CT therefore activates Pap1-dependent transcription by a novel mechanism.

PMID- 16278452
TI  - Saccharomyces cerevisiae Npc2p is a functionally conserved homologue of the human
      Niemann-Pick disease type C 2 protein, hNPC2.
AB  - Niemann-Pick Disease Type C (NP-C) is a fatal neurodegenerative disease, which is
      biochemically distinguished by the lysosomal accumulation of exogenously derived
      cholesterol. Mutation of either the hNPC1 or hNPC2 gene is causative for NP-C. We
      report the identification of the yeast homologue of human NPC2, Saccharomyces
      cerevisiae Npc2p. We demonstrate that scNpc2p is evolutionarily related to the
      mammalian NPC2 family of proteins. We also show, through colocalization,
      subcellular fractionation, and secretion analyses, that yeast Npc2p is treated
      similarly to human NPC2 when expressed in mammalian cells. Importantly, we show
      that yeast Npc2p can efficiently revert the unesterified cholesterol and GM1
      accumulation seen in hNPC2-/- patient fibroblasts demonstrating that it is a
      functional homologue of human NPC2. The present study reveals that the
      fundamental process of NPC2-mediated lipid transport has been maintained
      throughout evolution.

PMID- 16278453
TI  - Independent metalloregulation of Ace1 and Mac1 in Saccharomyces cerevisiae.
AB  - Ace1 and Mac1 undergo reciprocal copper metalloregulation in yeast cells. Mac1 is
      functional as a transcriptional activator in copper-deficient cells, whereas Ace1
      is a transcriptional activator in copper-replete cells. Cells undergoing a
      transition from copper-deficient to copper-sufficient conditions through a switch
      in the growth medium show a rapid inactivation of Mac1 and a corresponding rise
      in Ace1 activation. Cells analyzed after the transition show a massive
      accumulation of cellular copper. Under these copper shock conditions we show,
      using two epitope-tagged variants of Mac1, that copper-mediated inhibition of Mac
      function is independent of induced protein turnover. The transcription activity
      of Mac1 is rapidly inhibited in the copper-replete cells, whereas chromatin
      immunoprecipitation studies showed only partial copper-induced loss of DNA
      binding. Thus, the initial event in copper inhibition of Mac1 function is likely
      copper inhibition of the transactivation activity. Copper inhibition of Mac1 in
      transition experiments is largely unaffected in cells overexpressing copper
      binding proteins within the nucleus. Likewise, high expression of a copper
      binding, non-DNA-binding Mac1 mutant is without effect on the copper activation
      of Ace1. Thus, metalloregulation of Ace1 and Mac1 occurs independently.

PMID- 16278454
TI  - Comparison of cell wall localization among Pir family proteins and functional
      dissection of the region required for cell wall binding and bud scar recruitment
      of Pir1p.
AB  - We examined the localization of the Pir protein family (Pir1 to Pir4), which is
      covalently linked to the cell wall in an unknown manner. In contrast to the other
      Pir proteins, a fusion of Pir1p and monomeric red fluorescent protein distributed
      in clusters in pir1Delta cells throughout the period of cultivation, indicating
      that Pir1p is localized in bud scars. Further microscopic analysis revealed that
      Pir1p is expressed inside the chitin rings of the bud scars. Stepwise deletion of
      the eight units of the repetitive sequence of Pir1p revealed that one unit is
      enough for the protein to bind bud scars and that the extent of binding of Pir1p
      to the cell wall depends on the number of these repetitive units. The
      localization of a chimeric Pir1p in which the repetitive sequence of Pir1p was
      replaced with that of Pir4p revealed the functional role of the different protein
      regions, specifically, that the repetitive sequence is required for binding to
      the cell wall and that the C-terminal sequence is needed for recruitment to bud
      scars. This is the first report that bud scars contain proteins like Pir1p as
      internal components.

PMID- 16278455
TI  - Repressors Nrg1 and Nrg2 regulate a set of stress-responsive genes in
      Saccharomyces cerevisiae.
AB  - The yeast Saccharomyces cerevisiae responds to environmental stress by rapidly
      altering the expression of large sets of genes. We report evidence that the
      transcriptional repressors Nrg1 and Nrg2 (Nrg1/Nrg2), which were previously
      implicated in glucose repression, regulate a set of stress-responsive genes.
      Genome-wide expression analysis identified 150 genes that were upregulated in
      nrg1Delta nrg2Delta double mutant cells, relative to wild-type cells, during
      growth in glucose. We found that many of these genes are regulated by glucose
      repression. Stress response elements (STREs) and STRE-like elements are
      overrepresented in the promoters of these genes, and a search of available
      expression data sets showed that many are regulated in response to a variety of
      environmental stress signals. In accord with these findings, mutation of NRG1 and
      NRG2 enhanced the resistance of cells to salt and oxidative stress and decreased
      tolerance to freezing. We present evidence that Nrg1/Nrg2 not only contribute to
      repression of target genes in the absence of stress but also limit induction in
      response to salt stress. We suggest that Nrg1/Nrg2 fine-tune the regulation of a
      set of stress-responsive genes.

PMID- 16278456
TI  - Pho5p and newly identified nucleotide pyrophosphatases/ phosphodiesterases
      regulate extracellular nucleotide phosphate metabolism in Saccharomyces
      cerevisiae.
AB  - Extracellular nucleotides play many biological roles, including intercellular
      communication and modulation of nucleotide receptor signaling, and are dependent
      on the phosphorylation state of the nucleotide. Regulation of nucleotide
      phosphorylation is necessary, and a specialized class of enzymes, nucleotide
      pyrophosphatases/phosphodiesterases (E-NPPs), has been identified in mammals to
      perform this function. Although the E-NPP class is conserved among complex
      eukaryotes, this system has not yet been identified in Saccharomyces cerevisiae.
      Using genetic and biochemical experiments, we show that two orthologs of the E
      NPP family, referred to as Npp1p and Npp2p, exist in budding yeast and can
      perform nucleotide phosphate hydrolysis. This activity is enhanced during
      phosphate starvation, where hydrolyzed phosphates can be imported from
      extracellular sources and utilized to overcome phosphate starvation through the
      activity of the Pho5p acid phosphatase. The added compensatory effect by Pho5p is
      also a newly established role for Pho5p. This study demonstrates that
      extracellular nucleotide phosphate metabolism appears to be controlled by at
      least two independent regulatory mechanisms, uniting phosphate starvation with
      extracellular nucleotide regulation.

PMID- 16278458
TI  - A Rho-type GTPase, rho-4, is required for septation in Neurospora crassa.
AB  - Proteins in the Rho family are small monomeric GTPases primarily involved in
      polarization, control of cell division, and reorganization of cytoskeletal
      elements. Phylogenetic analysis of predicted fungal Rho proteins suggests that a
      new Rho-type GTPase family, whose founding member is Rho4 from the
      archiascomycete Schizosaccharomyces pombe, is involved in septation. S. pombe
      rho4Delta mutants have multiple, abnormal septa. In contrast to S. pombe
      rho4Delta mutants, we show that strains containing rho-4 loss-of-function
      mutations in the filamentous fungus Neurospora crassa lead to a loss of
      septation. Epitope-tagged RHO-4 localized to septa and to the plasma membrane. In
      other fungi, the steps required for septation include formin, septin, and actin
      localization followed by cell wall synthesis and the completion of septation. rho
      4 mutants were unable to form actin rings, showing that RHO-4 is required for
      actin ring formation. Characterization of strains containing activated alleles of
      rho-4 showed that RHO-4-GTP is likely to initiate new septum formation in N.
      crassa.

PMID- 16278457
TI  - A chitin synthase and its regulator protein are critical for chitosan production
      and growth of the fungal pathogen Cryptococcus neoformans.
AB  - Chitin is an essential component of the cell wall of many fungi. Chitin also can
      be enzymatically deacetylated to chitosan, a more flexible and soluble polymer.
      Cryptococcus neoformans is a fungal pathogen that causes cryptococcal
      meningoencephalitis, particularly in immunocompromised patients. In this work, we
      show that both chitin and chitosan are present in the cell wall of vegetatively
      growing C. neoformans yeast cells and that the levels of both rise dramatically
      as cells grow to higher density in liquid culture. C. neoformans has eight
      putative chitin synthases, and strains with any one chitin synthase deleted are
      viable at 30 degrees C. In addition, C. neoformans genes encode three putative
      regulator proteins, which are homologs of Saccharomyces cerevisiae Skt5p. None of
      these three is essential for viability. However, one of the chitin synthases
      (Chs3) and one of the regulators (Csr2) are important for growth. Cells with
      deletions in either CHS3 or CSR2 have several shared phenotypes, including
      sensitivity to growth at 37 degrees C. The similarity of their phenotypes also
      suggests that Csr2 specifically regulates chitin synthesis by Chs3. Lastly, both
      chs3Delta and the csr2Delta mutants are defective in chitosan production,
      predicting that Chs3-Csr2 complex with chitin deacetylases for conversion of
      chitin to chitosan. These data suggest that chitin synthesis could be an
      excellent antifungal target.

PMID- 16278459
TI  - Functional analysis of the polyketide synthase genes in the filamentous fungus
      Gibberella zeae (anamorph Fusarium graminearum).
AB  - Polyketides are a class of secondary metabolites that exhibit a vast diversity of
      form and function. In fungi, these compounds are produced by large, multidomain
      enzymes classified as type I polyketide synthases (PKSs). In this study we
      identified and functionally disrupted 15 PKS genes from the genome of the
      filamentous fungus Gibberella zeae. Five of these genes are responsible for
      producing the mycotoxins zearalenone, aurofusarin, and fusarin C and the black
      perithecial pigment. A comprehensive expression analysis of the 15 genes revealed
      diverse expression patterns during grain colonization, plant colonization, sexual
      development, and mycelial growth. Expression of one of the PKS genes was not
      detected under any of 18 conditions tested. This is the first study to
      genetically characterize a complete set of PKS genes from a single organism.

PMID- 16278460
TI  - snRNA and heterochromatin formation are involved in DNA excision during
      macronuclear development in stichotrichous ciliates.
AB  - Several models for specific excision of micronucleus-specific DNA sequences
      during macronuclear development in ciliates exist. While the template-guided
      recombination model suggests recombination events resulting in specific DNA
      excision and reordering of macronucleus-destined sequences (MDS) guided by a
      template, there is evidence that an RNA interference-related mechanism is
      involved in DNA elimination in holotrichous ciliates. We describe that in the
      stichotrichous ciliate Stylonychia, snRNAs homologous to micronucleus-specific
      sequences are synthesized during macronuclear differentiation. Western and in
      situ analyses demonstrate that histone H3 becomes methylated at K9 de novo during
      macronuclear differentiation, and chromatin immunoprecipitation revealed that
      micronucleus-specific sequences are associated with methylated H3. To link both
      observations, expression of a PIWI homolog, member of the RNA-induced silencing
      complex, was silenced. In these cells, the methylated micronucleus-specific
      histone H3 variant "X" is still present in macronuclear anlagen and no K9
      methylation of histone H3 is observed. We suggest that snRNA recruits chromatin
      modifying enzymes to sequences to be excised. Based on our and earlier
      observations, we believe that this mechanism is not sufficient for specific
      excision of sequences and reordering of MDS in the developing macronucleus and
      propose a model for internal eliminated sequence excision and MDS reordering in
      stichotrichous ciliates.

PMID- 16278461
TI  - Highly efficient tandem affinity purification of trypanosome protein complexes
      based on a novel epitope combination.
AB  - Tandem affinity purification (TAP) allows for rapid and efficient purification of
      epitope-tagged protein complexes from crude extracts under native conditions. The
      method was established in yeast and has been successfully applied to other
      organisms, including mammals and trypanosomes. However, we found that the
      original method, which is based on the TAP tag, consisting of a duplicate protein
      A epitope, a tobacco etch virus protease cleavage site, and the calmodulin
      binding peptide (CBP), did not yield enough recovery of transcription factor
      SNAPc (for small nuclear RNA-activating protein complex) from crude trypanosome
      extracts for protein identification. Specifically, the calmodulin affinity
      chromatography step proved to be inefficient. To overcome this problem, we
      replaced CBP by the protein C epitope (ProtC) and termed this new epitope
      combination PTP tag. ProtC binds with high affinity to the monoclonal antibody
      HPC4, which has the unique property of requiring calcium for antigen recognition.
      Thus, analogous to the calcium-dependent CBP-calmodulin interaction, ProtC-tagged
      proteins can be released from immobilized HPC4 by a chelator of divalent cations.
      While this property was retained, epitope substitution improved purification in
      our experiments by eliminating the inefficiency of calmodulin affinity
      chromatography and by providing an alternative way of elution using the ProtC
      peptide in cases where EGTA inactivated protein function. Furthermore, HPC4
      allowed highly sensitive and specific detection of ProtC-tagged proteins after
      protease cleavage. Thus far, we have successfully purified and characterized the
      U1 small nuclear ribonucleoprotein particle, the transcription factor complex
      TATA-binding protein related factor 4 (TRF4)/SNAPc/transcription factor IIA
      (TFIIA), and RNA polymerase I of Trypanosoma brucei.

PMID- 16278463
TI  - The NIT1 promoter allows inducible and reversible silencing of centrin in
      Chlamydomonas reinhardtii.
AB  - An inverted repeat corresponding to parts of the centrin gene of Chlamydomonas
      reinhardtii was placed downstream of the NIT1 promoter, which is induced by
      ammonium starvation. After induction, transformants developed centrin deficiency
      as assayed by immunofluorescence, Western blotting, and Northern blotting. The
      effect was reversible, demonstrating that the NIT1 promoter allowed controlled
      RNA interference in Chlamydomonas reinhardtii.

PMID- 16278465
TI  - The changing face of prostate cancer.
AB  - Prostate cancer remains the most common noncutaneous human malignancy, and the
      second most lethal tumor among men. However, the natural history of the disease
      is often prolonged, and the survival benefits of local therapy for men with low
      risk tumors may not be realized for a decade or more, as is increasingly well
      demonstrated in long-term observational cohorts in both the United States and
      Europe. A significant proportion of men with prostate cancer may be
      overdiagnosed, in the sense that diagnosis may not improve their lifespan or
      quality of life. However, the extent to which overdiagnosis represents a true
      problem relates to the consistency with which diagnosis leads invariably to
      active treatment. Prostate cancer is diagnosed at progressively earlier stages
      and with lower risk features; despite these trends, patients are less likely now
      than a decade ago to undergo a trial of active surveillance. Rates of
      brachytherapy and hormonal therapy use, in particular, have risen markedly.
      Important progress has been made in recent years in prostate cancer risk
      assessment. These advances, in combination with biomarkers in later stages of
      development, should be expected in the coming years to yield further improvements
      in clinicians' ability to diagnose prostate cancer early, and guide appropriately
      selected patients toward increasingly tailored treatment.

PMID- 16278462
TI  - Trichomonas vaginalis lipophosphoglycan mutants have reduced adherence and
      cytotoxicity to human ectocervical cells.
AB  - The extracellular human pathogen Trichomonas vaginalis is covered by a dense
      glycocalyx thought to play a role in host-parasite interactions. The main
      component of the glycocalyx is lipophosphoglycan (LPG), a polysaccharide anchored
      in the plasma membrane by inositol phosphoceramide. To study the role of LPG in
      trichomonads, we produced T. vaginalis LPG mutants by chemical mutagenesis and
      lectin selection and characterized them using morphological, biochemical, and
      functional assays. Two independently selected LPG mutants, with growth rates
      comparable to that of the wild-type (parent) strain, lost the ability to bind the
      lectins Ricinnus comunis agglutinin I (RCA120) and wheat germ agglutinin,
      indicating alterations in surface galactose and glucosamine residues. LPG
      isolated from mutants migrated faster than parent strain LPG on sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, suggesting the mutants had shorter
      LPG molecules. Dionex high-performance anion exchange chromatography with pulsed
      amperometric detection analyses revealed galactosamine, glucosamine, galactose,
      glucose, mannose/xylose, and rhamnose as the main monosaccharides of T. vaginalis
      parent strain LPG. LPG from both mutants showed a reduction of galactose and
      glucosamine, corresponding with the reduced size of their LPG molecules and
      inability to bind the lectins RCA120 and wheat germ agglutinin. Mutant parasites
      were defective in attachment to plastic, a characteristic associated with
      avirulent strains of T. vaginalis. Moreover, the mutants were less adherent and
      less cytotoxic to human vaginal ectocervical cells in vitro than the parental
      strain. Finally, while parent strain LPG could inhibit the attachment of parent
      strain parasites to vaginal cells, LPG from either mutant could not inhibit
      attachment. These combined results demonstrate that T. vaginalis adherence to
      host cells is LPG mediated and that an altered LPG leads to reduced adherence and
      cytotoxicity of this parasite.

PMID- 16278466
TI  - Role of diet in prostate cancer development and progression.
AB  - Increasing evidence supports the important role of nutrition in cancer
      prevention, including prevention of prostate cancer. In this review, we summarize
      data for some of the most consistently observed dietary associations for prostate
      cancer incidence, briefly consider possible postdiagnostic effects of nutrition
      on prostate cancer progression/survival, discuss new but limited data on diet
      gene interactions, and comment on current areas of controversy for future
      research focus. Potential protective dietary elements include tomatoes/lycopene,
      other carotenoids, cruciferous vegetables, vitamin E, selenium, fish/marine omega
      3 fatty acids, soy, isoflavones and polyphenols; whereas milk, dairy, calcium,
      zinc at high doses, saturated fat, grilled meats, and heterocyclic amines may
      increase risk. It is important to note that randomized clinical trial data exist
      only for vitamin E, calcium, beta-carotene, and selenium (all of which suggest
      inverse or no association). Several genes, such as MnSOD, XRCC1, and GST, may
      modify the association of specific nutrients and foods with prostate cancer risk;
      and further research is warranted to confirm these initial observed
      relationships. Until further clinical trial data are available on specific
      supplements and prostate cancer prevention, it would be prudent to emphasize a
      diet consisting of a wide variety of plant-based foods and fish; this is similar
      to what is recommended (and what is more well established) for the primary
      prevention of heart disease.

PMID- 16278467
TI  - Phase III prostate cancer prevention trials: are the costs justified?
AB  - One randomized, prospective clinical trial for chemoprevention of prostate cancer
      has been completed, and two additional trials are ongoing. The investment, time,
      and effort for these trials are substantial. We reviewed the outcomes of these
      trials to address the value of the investment. The outcomes of the Prostate
      Cancer Prevention Trial (testing finasteride) and the design of the Selenium and
      Vitamin E Cancer Prevention Trial (SELECT; testing vitamin E and selenium) trial
      as well as the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial
      (testing dutasteride) were reviewed. From a public health standpoint, there is
      tremendous potential for benefit from large-scale cancer prevention trials.
      Because of the volume of data that are collected, potential discoveries related
      to the biology of the disease are substantial. Translational scientific efforts
      are direct outgrowths of these studies. Prospective, randomized chemoprevention
      trials for prostate and other cancers are expensive and require long periods of
      time to conduct, yet the rewards are on a par with the investment.

PMID- 16278468
TI  - Active surveillance for prostate cancer: for whom?
AB  - Prostate-specific antigen (PSA) -based prostate cancer screening results in the
      diagnosis of prostate cancer in many men who are not destined to have clinical
      progression during their lifetime. Good-risk prostate cancer, defined as a
      Gleason score of 6 or less, PSA < 10, and T1c to T2a, now constitutes 50% of
      newly diagnosed prostate cancer. In most of these patients, the disease is
      indolent and slow growing. The challenge is to identify those patients who are
      unlikely to experience significant progression while offering radical therapy to
      those who are at risk. The approach to favorable-risk prostate cancer described
      in this article uses estimation of PSA doubling time (PSA DT) to stratify
      patients according to the risk of progression. Patients who select this approach
      are managed initially with active surveillance. Those who have a PSA DT of 3
      years or less (based on a minimum of three determinations over 6 months) are
      offered radical intervention. The remainder are closely monitored with serial PSA
      and periodic prostate rebiopsies (at 2, 5, and 10 years). In this series of 299
      patients, the median DT was 7 years. Forty-two percent had a PSA DT > 10 years,
      and 20% had a PSA DT > 100 years. The majority of patients on this study remain
      under surveillance. The approach of active surveillance with selective delayed
      intervention based on PSA DT represents a practical compromise between radical
      therapy for all (which results in overtreatment for patients with indolent
      disease) and watchful waiting with palliative therapy only (which results in
      undertreatment for those with aggressive disease).

PMID- 16278469
TI  - Robotic-assisted laparoscopic prostatectomy: do minimally invasive approaches
      offer significant advantages?
AB  - Radical prostatectomy has maintained a cardinal role in the treatment of
      localized prostate cancer. Robotic-assisted laparoscopic prostatectomy (RALP) has
      been introduced as a less invasive surgical approach. Available data on RALP
      versus open approaches were reviewed for surgical and cancer related outcomes.
      RALP is consistently associated with decreased blood loss and limited
      postoperative pain and hospital stay. Surgical margins seem similar between most
      reported series of RALP or open radical prostatectomy. Most intrainstitutional
      comparisons demonstrate better postoperative continence and potency with RALP,
      but there is still debate about whether results are superior to radical
      retropubic prostatectomy in the hands of a highly experienced surgeon. RALP
      provides outcomes at least comparable, and, in some measures, superior to open
      surgery. Refinements of instrumentation may provide even better results in the
      future.

PMID- 16278470
TI  - Radiotherapy in the management of clinically localized prostate cancer: evolving
      standards, consensus, controversies and new directions.
AB  - Major advances have been made in the definitive use of various forms of
      radiotherapy (RT) in the management of clinically localized prostate cancer
      (PCa). Despite tremendous gains, the radiation oncology community continues to
      struggle with several key questions. In general, the areas of controversy pertain
      to how to improve the therapeutic ratio of RT. Specifically, key issues include
      dose escalation; the relative benefit of alternative forms of RT (ie,
      brachytherapy and protons); target localization; the use, timing, and duration of
      androgen deprivation; and the need for pelvic nodal irradiation. Multiple efforts
      have been made to address each of these issues; however, there is no consensus on
      how to resolve them. This review is an evidence-based critique of the available
      treatment approaches considered for the optimal use of radiotherapy as definitive
      management of clinically localized PCa.

PMID- 16278471
TI  - High-risk localized prostate cancer: a case for early chemotherapy.
AB  - High-risk tumors exhibit a more aggressive natural history and have higher
      positive margin and recurrence rates after radical prostatectomy or radiotherapy
      alone, where unimodality therapy likely represents undertreatment. Hence, the
      therapeutic ratio (patients who actually realize a survival benefit from a
      therapeutic intervention) may, therefore, be greater in high-risk disease if its
      natural history can be altered by multimodality therapy. It is, thus, important
      to investigate therapies that optimize complete extirpation of all cancer cells
      and reduce the incidence of positive surgical margins and disease recurrence.
      Neoadjuvant therapy extends the logic of early adjuvant therapy further by
      applying systemic therapy earlier in the course of the disease before definitive
      locoregional therapy. In prostate cancer, outcomes have not been improved
      significantly when neoadjuvant hormone therapy is used before surgery; although
      outcomes are improved when androgen ablation is combined with radiotherapy, many
      patients remain at risk for systemic recurrence. With recent data confirming
      improved survival data with docetaxel chemotherapy in metastatic disease, future
      trials are now focusing on earlier combinations of chemohormonal or biologic
      therapies in high-risk patients.

PMID- 16278472
TI  - Utility of prostate-specific antigen kinetics in addition to clinical factors in
      the selection of patients for salvage local therapy.
AB  - A detectable and rising prostate-specific antigen (PSA) level after radical
      prostatectomy or a rising PSA above the nadir value after radiation therapy may
      represent a local failure, distant failure, or both. Determining the site or
      sites of failure is critical for selecting the appropriate salvage therapy.
      Nevertheless, although PSA failure precedes clinically evident failure by several
      years, determining the source of the biochemical failure is often not possible
      using currently available diagnostic studies. Selecting the optimal therapeutic
      approach may be guided by the initial clinical factors (eg, T-category, PSA,
      biopsy Gleason score). If the patient has had a radical prostatectomy, then the
      pathologic outcomes of the surgery (eg, pathologic T-category and prostatectomy
      Gleason score, nodal and margin status) may provide further information. Beyond
      pretreatment clinical and post-treatment pathologic factors, PSA kinetics, and
      specifically a pretreatment PSA velocity > 2 ng/mL/year, an interval to PSA
      failure < 3 years and a post-treatment PSA doubling time < 3 months place a man
      at increased risk for metastases and subsequent prostate cancer-specific
      mortality, making these men poor candidates for local-only salvage therapy.
      Therefore, the optimal candidate for local-only salvage therapy is a man whose
      pretreatment PSA velocity was 2 ng/mL/year or less, interval to PSA failure
      exceeds 3 years, and post-treatment PSA doubling time is at least 12 months, and
      who did not have biopsy or prostatectomy Gleason score of 8 to 10 or seminal
      vesicle or lymph node involvement.

PMID- 16278473
TI  - Role of salvage radical prostatectomy for recurrent prostate cancer after
      radiation therapy.
AB  - Patients with isolated local recurrence of prostate cancer after radiation
      therapy may potentially be cured of their disease by salvage radical
      prostatectomy (RP). The stage-specific 5-year cancer-control rates of salvage RP
      resemble those of standard RP. However, the ability to effectively administer
      salvage treatment to patients with radiorecurrent disease is compromised by the
      lack of diagnostic tests with sufficient sensitivity and specificity to detect
      local recurrence at an early stage while it is amenable to local salvage therapy.
      By the time biochemical recurrence is declared using the current American Society
      for Therapeutic Radiology and Oncology definition, the majority of patients have
      advanced local disease, precluding successful local salvage therapy. When salvage
      RP is performed at prostate-specific antigen levels of 10 ng/mL or less, an
      estimated 70% of patients are free of disease at 5 years. With better patient
      selection and technical modifications, the morbidity associated with salvage RP
      has improved substantially. Rates of urinary incontinence and anastomotic
      stricture are acceptable, although one third of patients will experience these
      complications. Salvage cryotherapy is a minimally invasive alternative to salvage
      RP, but cancer-control rates appear to be inferior and it does not provide a
      clear advantage over salvage RP in terms of reduced morbidity. Patients with
      local recurrence after radiation therapy are at increased risk of metastatic
      progression and cancer-specific mortality. Currently, salvage RP represents the
      only curative treatment option for these patients. Salvage RP may favorably alter
      the natural history of biochemical recurrence after radiation therapy, but it
      must be instituted early in the course of recurrent disease to be effective.

PMID- 16278474
TI  - Parameters for treatment decisions for salvage radiation therapy.
AB  - Radical prostatectomy (RP) is the most common primary treatment for prostate
      cancer. About 40% of those with high-risk pathologic features, such as a positive
      margin or seminal vesicle involvement, will develop biochemical failure at some
      point in the future. Radiotherapy (RT), with or without concurrent androgen
      deprivation, has been used liberally in the management of men with a rising
      prostate-specific antigen (PSA) after RP, based mostly on relatively small
      retrospective series. Factors such as the prostatectomy Gleason score, seminal
      vesicle invasion, absolute pre-RT PSA level, and pre-RT PSA doubling time are
      emerging as important determinants of outcome after RT. These factors should be
      used as a guide to the options of local therapy alone (RT), local therapy plus
      systemic therapy (typically androgen deprivation therapy), and systemic therapy
      alone.

PMID- 16278475
TI  - Should intermittent androgen deprivation be used in routine clinical practice?
AB  - For several decades, androgen deprivation (AD) has been the mainstay for treating
      metastatic prostate cancer. AD can be attained by a variety of means; however,
      irrespective of modality and a gratifying initial high response rate, almost all
      patients advance to a state of androgen independence and ultimately a hormone
      refractory state. Improved understanding of the biology and mechanisms of
      progression to androgen independence coupled with promising preclinical data have
      led to investigating intermittent AD (IAD) as a way of improving disease control
      while maintaining quality of life. Preliminary published clinical experience,
      mostly from uncontrolled trials, suggests the feasibility of this approach. Two
      ongoing cooperative-group phase III trials are evaluating the survival impact of
      IAD both in patients with metastatic disease and in those with prostate-specific
      antigen failure post-radiation therapy. There are several unanswered questions
      regarding this approach, and until more definitive data regarding its safety and
      impact on survival are available, IAD should be considered experimental. In this
      review, we detail the background and preclinical scientific rational for
      investigating IAD, and we review published clinical experience and describe the
      ongoing phase III clinical trials. We also discuss special considerations for
      using IAD outside the context of a clinical trial.

PMID- 16278476
TI  - Bisphosphonates for treatment and prevention of bone metastases.
AB  - Bone metastases are a major cause of morbidity for men with prostate cancer.
      Complications of bone metastases include pain, fractures, and spinal cord
      compression. Although they appear osteoblastic by radiographic imaging, most bone
      metastases are characterized by excess osteoclast number and activity. In
      addition, pathologic osteoclast activation is associated with increased risk of
      skeletal complications. Zoledronic acid, a potent inhibitor of osteoclast
      activity, differentiation, and survival, decreases the risk of skeletal
      complications in men with androgen-independent prostate cancer and bone
      metastases. Other bisphosphonates, including pamidronate and clodronate, seem to
      be ineffective in this setting. The reduction in risk of skeletal complications
      with zoledronic acid must be weighed against potential adverse effects.
      Additional studies are needed to determine the optimal timing, schedule, and
      duration of treatment in men with bone metastases as well as the potential role
      of bisphosphonates in other settings including the prevention of bone metastases.

PMID- 16278477
TI  - Early versus delayed androgen deprivation for prostate cancer: new fuel for an
      old debate.
AB  - The purpose of this review is to discuss the recent increase in data supporting
      the use of androgen ablation early in the clinical course for patients with
      nonmetastatic prostate cancer. We systematically reviewed recent publications
      that report on the use of androgen deprivation (AD) in nonmetastatic prostate
      cancer patients from the 2003 and 2004 proceedings of the American Society of
      Clinical Oncology, the 2003 and 2004 proceedings of the American Urological
      Association as well as published literature from 2003 to 2005. Five recently
      published mature randomized trials of AD plus local therapy were evaluated plus
      two large data sets on the use of AD for patients with serologic relapse after
      local therapy. Four mature randomized studies demonstrate an overall survival
      benefit to the use of AD in conjunction with definitive local therapy (three with
      radiation and one with surgery). One retrospective analysis suggests that AD
      administered early after serologic progression improves overall survival, and one
      retrospective analysis shows a reduction in metastasis-free survival but has not
      yet shown an overall survival benefit. For patients with nonmetastatic prostate
      cancer with high-risk features, as well as those for serologic relapse, the use
      of AD before the development of metastatic disease is supported by long-term
      outcomes from a series of clinical trials. Consideration of AD is therefore
      warranted early in the clinical course of high-risk patients.

PMID- 16278478
TI  - Pathogenesis and treatment of prostate cancer bone metastases: targeting the
      lethal phenotype.
AB  - Traditionally, prostate cancer treatment, as well as all cancer treatment, has
      been designed to target the tumor cell directly via various hormonal and
      chemotherapeutic agents. Recently, the realization that cancer cells exist in
      complex microenvironments that are essential for the tumorigenic and metastatic
      potential of the cancer cells is starting the redefine the paradigm for cancer
      therapy. The propensity of prostate cancer cells to metastasize to bone is
      leading to the design of novel therapies targeting both the cancer cell as well
      as the bone microenvironment. Tumor cells in the bone interact with the
      extracellular matrix, stromal cells, osteoblasts, osteoclasts, and endothelial
      cells to promote tumor-cell survival and proliferation leading to a lethal
      phenotype that includes increased morbidity and mortality for patients with
      advanced prostate cancer. Several strategies are being developed that target
      these complex tumor cell-microenvironment interactions and target the signal
      transduction pathways of other cells important to the development of metastases,
      including the osteoclasts, osteoblasts, and endothelial cells of the bone
      microenvironment. Current and new therapies in metastatic prostate cancer will
      comprise a multitargeted approach aimed at both the tumor cell and the tumor
      microenvironment. Here, we review the current therapeutic strategies for
      targeting the prostate cancer-bone microenvironment and several single- and
      multiagent targeted approaches to the treatment of advanced prostate cancer that
      are under development.

PMID- 16278479
TI  - Chemotherapy for hormone-refractory prostate cancer: now it's a question of
      "when?".
AB  - Recently, data from two randomized phase III studies that compared docetaxel
      based chemotherapy to mitoxantrone-based therapy demonstrated that treatment with
      docetaxel can prolong life in a significant way for patients with hormone
      refractory prostate cancer. For many patients who experience disease progression
      after androgen-deprivation therapy, however, chemotherapy may not be immediately
      indicated. Such cases include those individuals with hormone-refractory disease
      in the absence of clinical metastases, and those with asymptomatic metastatic
      disease, for example. As a result, clinicians treating patients with hormone
      refractory disease must weigh the benefits of earlier chemotherapy against its
      risks, and may consider other therapies such as secondary hormonal approaches
      before initiating chemotherapy. This decision is further complicated by the fact
      that a phase III study designed to compare secondary hormonal therapy with
      chemotherapy has failed due to lack of accrual. Furthermore, the limitations of
      chemotherapy for prostate cancer are being clarified and include a lack of
      standard second-line therapy as well as uncertain benefits for those with
      nonmetastatic disease. In this review, we will highlight some of the issues that
      impact on the decision of when to start chemotherapy and in whom as well as the
      potential benefits of secondary hormonal approaches.

PMID- 16278480
TI  - Management of advanced prostate cancer after first-line chemotherapy.
AB  - Hormone refractory prostate cancer (HRPC) causes substantial morbidity and
      mortality. There are increasing options for both first- and second-line therapy
      in the palliative treatment of patients with HRPC. Medications to control
      symptoms should first be optimized in patients with late-stage disease, and
      radiotherapy applied to dominant painful bone lesions. Docetaxel, mitoxantrone,
      satraplatin, and ixabepilone are active chemotherapeutic agents in the first-
      and/or second-line setting for patients with HRPC, and this may be true also of
      older drugs such as oral cyclophosphamide and vinorelbine. Radioisotopes such as
      strontium and samarium are useful for treatment of more generalized bone pain.
      Third-line hormonal maneuvers including glucocorticoids, ketoconazole, and
      estrogens can lead to further palliation in some patients, and there are
      provocative data that chemotherapy might restore hormonal sensitivity in a subset
      of patients.

PMID- 16278481
TI  - Biology of progressive, castration-resistant prostate cancer: directed therapies
      targeting the androgen-receptor signaling axis.
AB  - Prostate cancers that are progressing on medical and surgical therapies designed
      to ablate the action of androgens continue to express androgen receptor (AR) and
      to depend on signaling through the receptor for growth. A more clinically
      relevant classification of castration-resistant disease focuses on the mechanisms
      of receptor activation, which include (1) changes in the level of ligand(s) in
      tumor tissue; (2) increased levels of the protein due to gene amplification or
      altered mRNA expression; (3) activating mutations in the receptor that affect
      structure and function; (4) changes in coregulatory molecules including
      coactivators and corepressors; and (5) factors that lead to activation of the
      receptor independent of the level of ligand or receptor allowing kinase cross
      talk. From an AR perspective, the term "hormone refractory" is inappropriate. On
      the basis of this schema, we discuss strategies that are focused on the AR either
      directly or indirectly, as single agents or in combination, that are in clinical
      development.

PMID- 16278482
TI  - Prostate cancer immunology: biology, therapeutics, and challenges.
AB  - A number of recently developed and promising approaches to antitumoral
      immunotherapy are being investigated as potential treatments for advanced
      prostate cancer. These approaches largely revolve around strategies to increase
      antigen-specific T-cell activation against prostate tumors as well as precise
      manipulations of critical co-regulatory receptors that help to maintain and
      prolong the activity of antigen-presenting cells and T cells that are capable of
      mediating tumor regression. Herein, we describe the experience with the most
      recent and promising approaches pertaining to prostate cancer immunotherapy.
      Additionally, we discuss the mechanistic basis for these approaches as well as
      current limitations that must still be addressed in order to propel immunotherapy
      into the forefront of prostate cancer treatment.

PMID- 16278483
TI  - Radiation dose in spinal cord compression.

PMID- 16278484
TI  - Radiotherapy alone or surgery in spinal cord compression? The choice depends on
      accurate patient selection.

PMID- 16278485
TI  - Portal hypertension secondary to 90Yttrium microspheres: an unknown complication.

PMID- 16278486
TI  - Focus issue: memories of signals past--plastic changes in nervous system
      function.
AB  - Plasticity encompasses the ability of the nervous system to adapt to injury and
      the ability of the developing and mature brain to change in response to
      experience. This week's Special Issue of Science focuses on systems-level
      approaches to understanding cortical plasticity, especially during development.
      The accompanying Focus Issue of Science's STKE features articles and resources
      that address issues related to the molecular changes that underlie synaptic
      plasticity in response to physiological or pathological stimuli.

PMID- 16278487
TI  - Endocannabinoid identification in the brain: studies of breakdown lead to
      breakthrough, and there may be NO hope.
AB  - Endocannabinoids are a class of fatty acid derivatives defined by their ability
      to interact with the specific cannabinoid receptors that were originally
      identified as the targets of Delta9-tetrahydocannabinol (Delta9-THC), the
      psychoactive component of cannabis. Endocannabinoids have been implicated in a
      growing number of important physiological and behavioral events. A full
      understanding of the functions of endocannabinoids will involve knowing which
      ones are active, and how they are produced, during any given physical event.
      However, studying these small lipids in the brain presents many technical
      challenges. New selective pharmacological tools promise to be very useful in
      unraveling the complexities of endocannabinoid signaling, but parallel
      developments from the investigation of the cellular neurophysiology of the
      endocannabinoid systems highlight the difficulties remaining.

PMID- 16278488
TI  - Hijacking the ERK signaling pathway: Mycobacterium leprae shuns MEK to drive the
      proliferation of infected Schwann cells.
AB  - Schwann cells are the target of Mycobacterium leprae, the pathogen responsible
      for leprosy. Once inside the cell, M. leprae activates the host's proliferative
      machinery, thereby increasing the number of cells susceptible to infection. This
      astonishing manipulation of the mammalian cell cycle is the subject of recent
      work by Tapinos and Rambukkana, who show that M. leprae drives proliferation
      through a novel route to extracellular signal-regulated kinase (ERK). In this
      Perspective, we discuss this important piece of work and highlight the
      noncanonical pathway used by M. leprae to induce proliferation.

PMID- 16278489
TI  - The "ups and downs" of signaling cascades in addiction.
AB  - Drug addiction is a chronic disease characterized by compulsive drug use despite
      the severe negative consequences associated with it. Repeated exposure to drugs
      of abuse results in molecular adaptations in neuronal signaling pathways, which
      eventually manifest in the complex behavioral alterations that characterize
      addiction. These include tolerance, sensitization, dependence, drug craving, and
      relapse. In this Review, we focus on recent studies highlighting signaling
      cascades initiated by cocaine, as a representative of a drug of abuse with a
      defined site of action, and alcohol, as a drug with an undefined primary site of
      action. Specifically, we describe recent studies that emphasize the role of
      protein-protein interactions, phosphorylation, and compartmentalization in the
      molecular mechanisms that result in the cellular and behavioral adaptations that
      underlie addiction. Signaling cascades that contribute to addiction, as well as
      those that protect or delay the development of addiction, are presented.

PMID- 16278490
TI  - Teaching resources. Long-term potentiation: mechanisms of induction and
      maintenance.
AB  - Synapses in general exhibit various forms of plasticity; that is, the efficiency
      of transmission across the synapse can be potentiated or depressed in response to
      a prior history of stimulation. The persistence of the change in efficiency can
      be relatively brief, exemplified by post-tetanic potentiation (PTP), which decays
      within a few seconds. At the other extreme, very stable forms of plasticity, long
      term potentiation (LTP) and long-term depression (LTD), can be established at
      many synapses in the brain. LTP is often proposed as a candidate for the cellular
      basis of memory, but direct evidence for this hypothesis is lacking. That said, a
      large body of research has provided correlative evidence for LTP as a process
      that underlies memory formation. This lecture, which is a part of the course
      "Cell Signaling Systems: A Course for Graduate Students," describes LTP from a
      cell biological perspective. Topics include the signaling network responsible for
      LTP induction, evidence for upregulated postsynaptic mechanisms in LTP, and the
      role of gene expression regulation, at the transcriptional and translational
      levels, in the maintenance of LTP.

PMID- 16278491
TI  - Lipid posttranslational modifications. Farnesyl transferase inhibitors.
AB  - Some proteins undergo posttranslational modification by the addition of an
      isoprenyl lipid (farnesyl- or geranylgeranyl-isoprenoid) to a cysteine residue
      proximal to the C terminus. Protein isoprenylation promotes membrane association
      and contributes to protein-protein interactions. Farnesylated proteins include
      small GTPases, tyrosine phosphatases, nuclear lamina, cochaperones, and
      centromere-associated proteins. Prenylation is required for the transforming
      activity of Ras. Because of the high frequency of Ras mutations in cancer,
      farnesyl transferase inhibitors (FTIs) were investigated as a means to antagonize
      Ras function. Evaluation of FTIs led to the finding that both K- and N-Ras are
      alternatively modified by geranylgeranyl prenyltransferase-1 in FTI-treated
      cells. Geranylgeranylated forms of Ras retain the ability to associate with the
      plasma membrane and activate substrates. Despite this, FTIs are effective at
      inhibiting the growth of human tumor cells in vitro, suggesting that activity is
      dependent on blocking the farnesylation of other proteins. FTIs also inhibit the
      in vivo growth of human tumor xenografts and sensitize these models to
      chemotherapeutics, most notably taxanes. Several FTIs have entered clinical
      trials for various cancer indications. In some clinical settings, primarily
      hematologic malignancies, FTIs have displayed evidence of single-agent activity.
      Clinical studies in progress are exploring the antitumor activity of FTIs as
      single agents and in combination. This review will summarize the basic biology of
      FTIs, their antitumor activity in preclinical models, and the current status of
      clinical studies with these agents.

PMID- 16278493
TI  - The role of buspirone for the treatment of cerebellar ataxia in an older
      individual.
AB  - BACKGROUND: Buspirone, a 5HT-agonist and D2-dopamine antagonist/agonist, has
      modest beneficial effects in younger individuals with cerebellar ataxia. However,
      it is unclear whether it is beneficial and tolerable in older ataxic individuals.
      OBJECTIVE: To determine if an older individual with cerebellar ataxia would
      benefit from and tolerate buspirone. METHODS: We performed a single-subject,
      double-blinded, placebo-controlled randomized-phase study. The 80 year-old
      subject was to undergo six 4-week testing periods, divided randomly into three
      treatment and three placebo arms with a 2-week washout period between each arm.
      Treatment consisted of buspirone hydrochloride. Outcomes were clinical gait and
      balance testing, posturography testing, and subjective measurement of balance
      confidence. RESULTS: There were no statistically significant objective
      improvements with buspirone. The subject experienced a subjective improvement in
      balance confidence and tolerated treatment. CONCLUSIONS: Single-subject studies
      can help when it is unclear whether drug trial results with young subjects are
      generalizable to an older subject. This single-subject study determined that
      buspirone was tolerable but not clearly beneficial for an ataxic older
      individual.

PMID- 16278494
TI  - Can Canada sustain paediatric phase I trials? A national survey of cancer relapse
      in children.
AB  - BACKGROUND: Paediatric phase I trials are critical to the evaluation of new
      agents using standardized methodology. However a large proportion of paediatric
      patients in Canada do not have access to phase I therapy. OBJECTIVES: A National
      Paediatric Cancer Relapse Survey was conducted to collect preliminary data to
      evaluate the feasibility of multi-centre paediatric phase I trials within Canada.
      METHODS: A survey consisting of 20 individual questions was sent out to all of
      the 17 paediatric oncology centres in Canada. RESULTS: Fifteen centres (88%)
      responded to the survey. 1027 children are diagnosed with cancer each year in
      Canada while 241 present with recurrent cancer. Of the 85 patients who are
      considered to be eligible for phase I study each year, only 53% were referred for
      phase I therapy. Two centres have more than 10 eligible patients a year, while
      the remaining 13 centres have less than 10 eligible patients each year.
      CONCLUSIONS: We estimate that 20% of the eligible patients could be accrued to
      phase I trials and Canada may provide sufficient patient number, i.e. 25 to 30
      solid tumour patients every 2 years, to allow one multi-centre paediatric phase I
      trial to be completed over a 2-year period.

PMID- 16278492
TI  - Saturated fat-induced changes in Sf 60-400 particle composition reduces uptake of
      LDL by HepG2 cells.
AB  - The ability of human postprandial triacylglycerol-rich lipoproteins (TRLs),
      isolated after meals enriched in saturated fatty acids (SFAs), n-6 PUFAs, and
      MUFAs, to inhibit the uptake of 125I-labeled LDL by the LDL receptor was
      investigated in HepG2 cells. Addition of TRLs resulted in a dose-dependent
      inhibition of heparin-releasable binding, cell-associated radioactivity, and
      degradation products of 125I-labeled LDL (P < 0.001). SFA-rich Svedberg flotation
      rate (Sf) 60-400 resulted in significantly greater inhibition of cell-associated
      radioactivity than PUFA-rich particles (P = 0.016) and total uptake of 125I
      labeled LDL compared with PUFA- and MUFA-rich particles (P < 0.02). Normalization
      of the apolipoprotein (apo)E but not apoC-III content of the TRLs removed the
      effect of meal fatty acid composition, and addition of an anti-apoE antibody
      reversed the inhibitory effect of TRLs on the total uptake of 125I-labeled LDL.
      Real time RT-PCR showed that the SFA-rich Sf 60-400 increased the expression of
      genes involved in hepatic lipid synthesis (P < 0.05) and decreased the expression
      of the LDL receptor-related protein 1 compared with MUFAs (P = 0.008). In
      conclusion, these findings suggest an alternative or additional mechanism whereby
      acute fat ingestion can influence LDL clearance via competitive apoE-dependent
      effects of TRL on the LDL receptor.

PMID- 16278495
TI  - Are brand-name and generic warfarin interchangeable? A survey of Ontario patients
      and physicians.
AB  - BACKGROUND: The issue of therapeutic equivalence has been a source of controversy
      in Canada since the approval of generic warfarin products in 2000. OBJECTIVES: We
      surveyed Ontario patients and physicians on perceptions of generic warfarin and
      brand substitution. METHODS: Self-administered questionnaires employed 7.0-point
      Likert scales of agreement. Patient participants were drawn from a
      thromboembolism clinic in Hamilton, Ontario. Physician participants were from a
      random sample of 375 Ontario family physicians, internists, cardiologists and
      hematologists. RESULTS: Eighty-one patients responded: 52% female, mean age 63.4
      years and 63% brand-name warfarin users. Overall, 33% of respondents agreed or
      strongly agreed that they would feel comfortable taking generic warfarin.
      However, seventeen percent agreed or strongly agreed that generic warfarin was
      neither as safe nor as effective as brand-name warfarin, with this view more
      common amongst patients taking brand-name than those taking generic warfarin. One
      hundred and ten (29.3%) physicians returned the survey--29% females, mean age
      45.3 years, 22% family physicians. Forty-four percent agreed or strongly agreed
      that they would rather prescribe brand-name than generic warfarin for patients
      starting warfarin therapy, while 40.7% agreed or strongly agreed that they would
      not feel comfortable switching from brand-name to generic warfarin. However, only
      19.4% of physicians who had switched patients from brand-name to generic warfarin
      actually reported difficulties in managing the switch. CONCLUSION: While most
      patients and physicians appear to have accepted the principle of therapeutic
      equivalence of generic and brand-name warfarin, a sizable minority has concerns
      that could influence prescribing and compliance.

PMID- 16278496
TI  - Cardiovascular collapse from low dose bupivacaine.
AB  - Bupivacaine is a long-acting local anesthetic agent that is very widely used for
      cutaneous infiltration, peripheral nerve blocks, epidural anesthesia, and spinal
      anesthesia. Well-described cardiotoxic effects of bupivacaine and other members
      of its class include dysrhythmias, hypotension, and depression of cardiac output.
      The minimum IV dose of bupivacaine previously associated with significant
      toxicity in humans is 1.6 mg/kg. A case is reported of bradyasystolic arrest with
      post resuscitation shock, without significant central nervous system (CNS)
      toxicity, following the injection of less than 1.1 mg/kg bupivacaine in an adult.

PMID- 16278498
TI  - Compliance assessment in drug trials: has there been improvement in two decades?
AB  - BACKGROUND: Compliance is a key element in the success of therapy, both in
      practice and research. A study from 1974 demonstrated that compliance in clinical
      trials was only determined in 19% of studies requiring it. OBJECTIVES: The
      objective was to determine if there has been an improvement in compliance
      assessment in clinical trials. METHODS: All drug studies published in the British
      Medical Journal, Journal of Pediatrics, and Lancet from 1997 to 1999 were
      reviewed. Clinical trials were evaluated as to their measurement of compliance
      and the method of assessment. RESULTS: Of 303 studies in which the effects of
      drugs were reported, 165 required the incorporation of a measure of compliance,
      86 did not, and in 52, compliance could not be measured. Of the studies requiring
      estimation of compliance, compliance was evaluated in 78 (47%). This rate did not
      vary between the journals examined or between trials in adults or children. The
      most common methods used to evaluate compliance were pill count (33%) and self
      report (25%). The use of drug assays (14%) and close supervision (9%) was less
      common. Electronic devices and other methods were uncommonly used (5%). In 16% of
      cases, a combination of methods was used. CONCLUSION: Although the rate of
      evaluation of compliance in drug trials has improved over the past 25 years, it
      continues to be examined in less than half of the clinical studies of drug
      effects in which compliance assessment is required. This rate appears to be
      similar in paediatric and adult drug studies.

PMID- 16278497
TI  - Clinical data gap between phase III clinical trials (pre-marketing) and phase IV
      (post-marketing) studies: evaluation of etanercept in rheumatoid arthritis.
AB  - BACKGROUND: There are fundamental differences in design between phase III
      clinical trials and phase IV post-marketing studies that involve patient
      characteristics, the clinical setting (environment) and the manner of drug use.
      As well, many phase IV studies are extensions of randomized clinical trials
      (RCTs) and suffer from selection bias. OBJECTIVE: To determine if the data
      obtained from RCTs of etanercept (Enbrel) in the treatment of rheumatoid
      arthritis would be representative of the effects attainable in community
      practice. METHOD: An analysis was conducted comparing data from published RCTs of
      etanercept use in rheumatoid arthritis patients with data collected in a
      community based cohort study that was not an extension of an RCT. RESULTS:
      Baseline clinical data, such as tender or painful joint count, patient's global
      assessment, the heath assessment questionnaire, physical and mental component
      summary of the SF-36, and rheumatoid arthritis drug profile were significantly
      different between the patients receiving etanercept in the phase IV community
      cohort study and the patients enrolled in the RCTs. Differences in the baseline
      data for the control patients were also noted amongst the RCT studies. The
      treatment outcome, American College of Rheumatology (ACR) response rate of 20%,
      50% and 70% at 6 month, was the same between the cohort study and the RCTs, but
      at 12 months the clinical response was less for the community based patients than
      for the RCT patients. At 6 months there were fewer withdrawals involving
      community-based patients than RCT patients due to less frequent withdrawals
      associated with lack of efficacy. At 12 months the withdrawal rate due to either
      a lack of efficacy or from adverse events was similar between data sets.
      CONCLUSION: The data from the etanercept phase III RCTs may not reflect the
      characteristics of patients using etanercept in community practice, nor the
      clinical outcomes observed by RA patients at 12 months. These discrepancies may
      be derived from methodological differences in study design and patient selection.
      On the other hand, outcomes such as withdrawal rates at 12 months appear
      comparable between the two types of populations.

PMID- 16278500
TI  - Does the use of SSRIs reduce medical care utilization and expenditures?
AB  - BACKGROUND: Although selective serotonin reuptake inhibitors (SSRIs) are more
      expensive than tricyclic antidepressants (TCAs), SSRIs may reduce overall health
      costs compared with TCAs through improved compliance and reduced need for other
      medical care services. Economic evaluation studies using clinical trial or claims
      data have not accurately estimated the actual costs associated with
      antidepressants because they did not appropriately address two issues: the
      heterogeneity of SSRI and TCA users and the use of antidepressants for non
      indicated symptoms. AIMS OF THE STUDY: This study estimates the relative
      substitution effect of SSRIs on the overall utilization of outpatient and
      inpatient care and other prescription drugs compared to TCAs. This study
      identifies and controls for heterogeneities in diagnosis among SSRI and TCA users
      and looks for variations in substitution effects across utilization. METHODS: To
      estimate the direct effect of SSRIs compared with TCAs on the utilization of
      other medical care resources in a naturalistic setting, this study uses the
      Medical Expenditure Panel Survey, national panel survey data, from 1996 to 1998.
      The main model of analysis is a two-part regression: the first part is a probit
      model of any use and the second part is a log linear model of expenditures among
      users. Baseline physical health status, depression severity, and socioeconomic
      factors that could affect antidepressant choice and medical care utilization are
      controlled for. RESULTS: A considerable fraction of antidepressant use,
      especially among TCA users, is for reasons other than depression. After
      controlling for the heterogeneity in SSRI and TCA users, this study does not find
      consistent evidence of the substitution of SSRIs for other medical care. Although
      SSRIs, compared with TCAs, reduce overall outpatient visits and other
      prescription drugs, they increase the utilization of these services for
      depression. Antidepressant choice does not influence the utilization or
      expenditure level for inpatient services which composed the largest part of
      medical expenditure in this study sample. Results are robust when the analysis is
      restricted to the SSRI or TCA users with a depression diagnosis. DISCUSSION: The
      potential cost-incremental effect of SSRIs over TCAs for the treatment of
      depression can be compromised by the reduced utilization for symptoms other than
      depression among SSRI users. This study uses national survey data and takes into
      account the heterogeneity of SSRI and TCA users so the results can be generalized
      to real clinical practice. IMPLICATIONS FOR HEALTH CARE PROVISION: The costs
      associated with antidepressants are not only for the treatment of depression
      symptoms. Antidepressants are commonly prescribed for conditions for which the
      clinical and economic benefits are not established. This practice may lead to
      significant unnecessary healthcare expenses. IMPLICATIONS FOR HEALTH POLICIES:
      Antidepressant prescriptions for non-indicated conditions should be considered in
      setting policies designed to control costs associated with antidepressants and in
      developing clinical guidelines for antidepressant prescription. IMPLICATIONS FOR
      FUTURE RESEARCH: Future research on the economic evaluation of antidepressants
      should consider the use of antidepressants for health conditions other than
      depression. The economic incentives for and clinical benefits of the prescription
      of antidepressants for non-indicated conditions could be explored in future
      research.

PMID- 16278501
TI  - Racial disparities in prescription drug use for mental illness among population
      in US.
AB  - BACKGROUND: Racial minorities are a rapidly growing portion of the US population.
      Research suggests that racial minorities are more vulnerable to mental illness
      due to risk factors, such as higher rates of poverty. Given that the burden of
      mental illnesses is significant, equal likelihood of mental health services
      utilization is important to reduce such burden. Racial minorities have been known
      to use mental health services less than Whites. However, it is unclear whether
      racial disparity in prescription drug use for mental illnesses exists in a
      nationally representative sample. For a valid estimation of prescription drug use
      patterns, the characteristic in the distribution of prescription drug use should
      be accounted for in the estimation model. AIMS OF THE STUDY: This study is
      intended to document whether there was a disparity in psychiatric drug use in
      both extensive and intensive margins between Whites and three racial minorities:
      Blacks, Hispanics, and Asian-Indians. The study looked at several specified
      mental illnesses, controlling for underlying health status and other confounding
      factors. METHODS: Secondary data analysis was conducted using the multiyear
      Medical Expenditure Panel Survey (MEPS), a nationally representative panel sample
      from 1996 through 2000. This analysis provides estimates of the actual
      expenditure on prescription drug use for people with specified mental illnesses
      for this study, based on comparison of Whites and other racial minorities. We
      derived the estimates from the two-part model, a framework that adjusts the
      likelihood of using prescription drugs for the specified mental illnesses while
      estimating the total actual expenditures on prescription drugs among the users.
      RESULTS: This study found that Blacks, Hispanics, and Asian-Indians were less
      likely than Whites to use prescription drugs by 8.3, 6.1 and 23.6 percentage
      points, respectively, holding other factors constant in the sample, with at least
      one of the specified mental illnesses. The expenditure on prescription drugs for
      the specified mental illnesses differs between each of racial minorities (Blacks,
      Hispanics, and Asian-Indians) and Whites even after adjusting for the different
      likelihood of using those prescription drugs. Blacks, Hispanics, and Asian
      Indians with the specified mental illnesses were estimated to spend 606.53 US
      dollars, 9.83 US dollars and 179.60 US dollars less per year, respectively, on
      their actual prescription drugs than Whites. DISCUSSION: This study concludes
      that three racial minorities: Blacks, Hispanics, and Asian-Indians, with the
      specified mental illnesses are less likely to use psychiatric drugs than Whites.
      Among users, racial minorities use less psychiatric drugs than Whites in terms of
      actual spending on those drugs. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE:
      There is a need to focus on a program to reach out to racial minorities with a
      diagnosis of mental illnesses, and this program should consider the cultural
      specificity of each minority group regarding mental illnesses. IMPLICATIONS FOR
      HEALTH POLICIES: In the development of mental health policy, it is crucial to
      understand the underlying non-socioeconomic factors which may significantly
      determine the access to mental health service. Also, education programs or other
      outreach programs for racial minorities are necessary to understand the different
      distribution of mental health services for racial minorities. IMPLICATIONS FOR
      FURTHER RESEARCH: Future research should examine the causes for racial disparity
      in the use of prescription drugs for mental illness both in the extensive and
      intensive margins. An in-depth analysis is needed to map out the attributes for
      the observed disparity between Whites and racial minorities in mental health
      service use.

PMID- 16278502
TI  - The impact of depression on the academic productivity of university students.
AB  - BACKGROUND: Depression is a common disorder that impacts an individual's ability
      to perform life activities, including those required by the workplace. Academic
      performance can be viewed as a direct parallel to workforce performance, with
      students belonging to a unique set of individuals whose ability to perform can be
      measured on criteria applied by an observer and by self-report. While the
      prevalence of depression for this group is high and preparation for entry into
      the workplace is critical for these individuals, this relationship has not been
      adequately investigated. AIMS OF THE STUDY: This study investigates the
      relationship between depression and its treatments and the academic performance
      of undergraduate students. METHODS: Data regarding academics, health and
      productivity for students from Western Michigan University were obtained from the
      University's Registrar's Office, the campus Health Center and a survey delivered
      to the students. The primary outcomes of interest were the student's grade point
      average (GPA), an objective, observer generated measure of academic productivity,
      and the students' self-reported academic performance. RESULTS: Diagnosed
      depression was associated with a 0.49 point, or half a letter grade, decrease in
      student GPA, while treatment was associated with a protective effect of
      approximately 0.44 points. The self-reported data regarding the impact of
      depression on the performance of academic tasks was consistent with these
      findings. Depressed students reported a pattern of increasing interference of
      depression symptoms with academic performance peaking in the month of diagnosis
      and decreasing thereafter with the lowest levels reported in months 4 through 6
      post-diagnosis, each of which is significantly less than the month of diagnosis.
      DISCUSSION: The finding of a significant relationship between depression and
      academic performance was robust to the variety of analyses employed within this
      study. However, interpretation of the findings must be tempered by a number of
      facts. The sample was drawn from a subset of students at a single university,
      those willing to complete a questionnaire regarding their health and
      productivity. Due to non-availability of the treatment data from other health
      care providers, the treatment variable used within the regression models
      represents an imprecise proxy for the totality of treatment methods received by
      depressed subjects from a variety of on-campus and off-campus health care
      providers. Another challenge to the interpretation of this data is the
      interrelatedness of depression and school performance. Because of this, it was
      not possible to evaluate the extent to which the association between depression
      and academic performance is driven by causality in either direction. IMPLICATIONS
      FOR HEALTH CARE PROVISION AND USE: While depression and its effects have been
      studied in many different population groups and subgroups, the effect of this
      disease on college students has not been well documented. This research
      demonstrates the impact of depression and the effectiveness of its treatment on a
      student sample. From a public health perspective, this analysis highlights the
      importance of access to mental health treatment facilities among the college aged
      and the potential value of efforts to educate this population segment on the
      availability of that resource.

PMID- 16278503
TI  - An analysis of the costs of treating schizophrenia in Spain: a hierarchical
      Bayesian approach.
AB  - BACKGROUND: Health care decisions should incorporate cost of illness and
      treatment data, particularly for disorders such as schizophrenia with a high
      morbidity rate and a disproportionately low allocation of resources. Previous
      cost of illness analyses may have disregarded geographical aspects relevant for
      resource consumption and unit cost calculation. AIMS: To compare the utilisation
      of resources and the care costs of schizophrenic patients in four mental-health
      districts in Spain (in Madrid, Catalonia, Navarra and Andalusia), and to analyse
      factors that determine the costs and the differences between areas. METHODS: A
      treated prevalence bottom-up three year follow-up design was used for obtaining
      data concerning socio-demography, clinical evolution and the utilisation of
      services. 1997 reference prices were updated for years 1998-2000 in euros. We
      propose two different scenarios, varying in the prices applied. In the first
      (Scenario 0) the reference prices are those obtained for a single geographic
      area, and so the cost variations are only due to differences in the use of
      resources. In the second situation (Scenario 1), we analyse the variations in
      resource utilisation at different levels, using the prices applicable to each
      healthcare area. Bayesian hierarchical models are used to discuss the factors
      that determine such costs and the differences between geographic areas. RESULTS:
      In scenario 0, the estimated mean cost was 4918.948 euros for the first year. In
      scenario 1 the highest cost was in Gava (Catalonia) and the lowest in Loja
      (Andalusia). Mean costs were respectively 4547.24 and 2473.98 euros. With respect
      to the evolution of costs over time, we observed an increase during the second
      year and a reduction during the third year. Geographical differences appeared in
      follow-up costs. The variables related to lower treatment costs were: residence
      in the family household, higher patient age and being in work. On the contrary,
      the number of relapses is directly related to higher treatment costs. No
      differences were observed between health areas concerning resource utilisation.
      DISCUSSION: Calculating the costs of a given disease involves two principal
      factors: the resource utilisation and the prices. In most studies, emphasis is
      placed on the analysis of resource utilisation. Other evaluations, however, have
      recognized the implications of incorporating different prices into the final
      results. In this study we show both scenarios. The factors that determine the
      cost of schizophrenia for the Spanish case are similar to the factors encountered
      in studies carried out in other countries. IMPLICATIONS FOR HEALTH POLICIES:
      Treatment costs may be reduced by the prevention of psychotic symptoms and
      relapse. IMPLICATIONS FOR FUTURE RESEARCH: The use of the same price data in
      multicentre studies may not be realistic. More effort should be made to obtain
      price data from all the centres or countries participating in a study. In the
      present study, only direct healthcare and social costs have been included. Future
      research should consider informal and indirect costs.

PMID- 16278505
TI  - Polish Registry of Congenital Malformations - aims and organization of the
      registry monitoring 300 000 births a year.
AB  - In 1997, the Polish Registry of Congenital Malformations (PRCM) was established,
      to fulfil epidemiological, prophylactic, socioeconomic and scientific functions.
      The PRCM is a population-based registry monitoring currently about 300 000 births
      a year in 13 provinces. Such a large area and population require a special
      organizational structure of the Registry. The PRCM Central Working Group and the
      computer database are located in the Department of Medical Genetics, University
      of Medical Sciences, Poznan. Here the data are collected, validated, encoded
      according to the ICD-10, and analysed. Provincial Working Groups are responsible
      for supervision of data collection in the given province. The PRCM staff has
      grown from about 250 members in 1997 to more than 400 members today. The PRCM
      collects information on structural defects diagnosed before the end of the second
      year of life. Minor anomalies are excluded from the registry. The main source of
      information is a registration form filled up by the physician diagnosing the
      anomaly. Since 2004 also electronic reporting has been possible. On 28 September
      2005 there were 54 020 entries in the database concerning 33 729 children with at
      least one congenital malformation and 1261 control entries concerning children
      without malformations. The PRCM is also an important source of identification of
      families at genetic risk. Education of physicians and the community in the field
      of genetic counselling is also an important aim of the PRCM. Since 2001, the PRCM
      has been a member of the Eurocat. Detailed information on PRCM organization,
      electronic reporting, and results are available at the PRCM website
      (www.rejestrwad.pl).

PMID- 16278506
TI  - Isolation of low-molecular-weight glutenin subunit genes from wild emmer wheat
      (Triticum dicoccoides).
AB  - Three low-molecular-weight glutenin subunit (LMW-GS) genes, designated LMW-Td1,
      LMW-Td2 and LMW-Td3, were isolated from wild emmer wheat (Triticum dicoccoides),
      which is the tetraploid progenitor of common wheat (T. aestivum). The complete
      nucleotide sequence lengths of LMW-Td1, LMW-Td2 and LMW-Td3 are 858, 900 and 1062
      bp, respectively. LMW-Td1 and LMW-Td3 can encode proteins with 284 and 352 amino
      acid residues, respectively, whereas LMW-Td2 is a putative pseudogene due to the
      presence of 3 inframe stop codons in its C-terminal domain. The deduced protein
      sequences of the 3 genes share the same typical polypeptide structures with known
      LMW-GS genes containing 8 cysteines in the mature protein domains. LMW-Td1 was
      clearly distinguished from all known LMW-GS genes, and considered as a novel LMW
      GS gene. Two hydrophobic motifs (i.e. PIIIL and PVIIL) were observed in the
      repetitive domain of LMW-Td3. Sequence comparison indicates that sequences of the
      3 LMW-GS genes from this study are strongly similar to known LMW-GS genes. Our
      phylogenetic analysis suggests that LMW-Td1 and LMW-Td2 are homologous with genes
      on chromosome 1A, and LMW-Td3 is closely related to genes on chromosome 1B.

PMID- 16278507
TI  - PstIAFLP based markers for leaf rust resistance genes in common wheat.
AB  - The aim of the present study was to detect candidate DNA markers for selected
      leaf rust resistance genes. A total number of 286 loci in the 'Thatcher' near
      isogenic lines carrying resistance gene Lr1, Lr9, Lr10, Lr13, Lr19, Lr21, Lr24,
      Lr26, Lr28, Lr35, and Lr37 were screened for DNA polymorphism by the PstIAFLP
      method. A survey with 33 selective primers yielded 16 candidate markers. Further
      validation studies on cultivars characterized for the presence and absence of
      selected resistance genes confirmed specificity of markers for Lr24, Lr26 and
      Lr37. The AFLP-based marker P42-530 was successfully converted into an STS
      marker. The new marker was linked with the Lr37-specific marker (CslVrga13) at
      the distance of 1.7 cM. The PstIAFLP method was found to be effective in the
      identification of DNA changes induced in hexaploid wheat by translocations from
      Agropyron elongatum, Secale cereale and Aegilops ventricosa.

PMID- 16278508
TI  - Cytological characteristics of F2 hybrids between Triticum aestivum L. and T.
      durum Desf. with reference to wheat breeding.
AB  - Cytological and agronomic characteristics of a F2 population from Triticum
      aestivum L. x T. durum Desf. hybrids were analyzed plant by plant. Means of
      morphologic traits in the F2 population were similar to those of the low-value
      parent. On average, F2 hybrids had 36.54 chromosomes per plant, indicating that
      each gamete lost 2.73 chromosomes at meiosis of the F1 generation. More than half
      of plants had 36-39 chromosomes, so male gametes with 19-21 chromosomes seemed to
      be superior to the others. The distribution frequency of chromosomes in this
      study differed from that in a previous report, where a different tetraploid wheat
      was used. This shows that a different breeding strategy may need to be taken when
      exploiting a different tetraploid wheat. According to our results, some plants
      with 42 chromosomes, having all the wheat A, B and D chromosomes, would appear in
      the F3 population, which provides a chance to obtain stable bread wheat lines
      from the self-pollinated progenies. Alternatively, the desirable individuals of
      the F2 population were backcrossed to bread wheat, which is very useful and
      efficient for the improvement of bread wheat by exploiting desirable genes in
      durum wheat.

PMID- 16278509
TI  - Rye SCAR markers for male fertility restoration in the P cytoplasm are also
      applicable to marker-assisted selection in the C cytoplasm.
AB  - The study aimed at testing the usefulness of recently developed SCAR markers on
      rye (Secale cereale L.) chromosome 4R in hybrid breeding based on the C source of
      male sterility-inducing cytoplasm. Of 10 markers studied, 4 revealed
      polymorphisms between 2 inbred lines (544cms-C and Ot0-20) crossed to develop F2
      and BC1 mapping populations. Analyses performed on 94 F2 and 93 BC1 plants
      allowed to extend a formerly constructed genetic map of chromosome arm 4RL. Three
      SCAR markers (SCP14M55, SCP15M55 and SCP16M58) were mapped in the vicinity of
      gene Rfc1, which restores male fertility in the C cytoplasm. The 3 tested SCAR
      markers proved to be effective in marker-assisted selection (MAS) for male
      fertility/sterility.

PMID- 16278510
TI  - Genetic relationships among wheat genotypes, as revealed by microsatellite
      markers and pedigree analysis.
AB  - Genetic relationships among 20 elite wheat genotypes were studied using
      microsatellite markers and pedigree analysis. A total of 93 polymorphic bands
      were obtained with 25 microsatellite primer pairs. Coefficient of parentage (COP)
      values were calculated using parentage information at the expansion level of 5.
      The pedigree-based similarity (mean 0.115, range 0.00-0.53) was lower than the
      similarity assessed using microsatellite markers (mean 0.70, range 0.47-0.91).
      Similarity estimates were used to construct dendrograms by using the unweighted
      pair-group method with arithmetic averages (UPGMA). Clustering of genotypes in
      respect of marker-based similarity revealed two groups. Genotype PBW442 diverged
      and appeared as distinct from all other genotypes in both marker-based and
      pedigree-based analysis. The correlation of COP values with genetic similarity
      values based on microsatellite markers is low (r = 0.285, p < 0.05). The results
      indicate a need to develop wheat varieties with a diverse genetic background and
      to incorporate new variability into the existing wheat gene pool.

PMID- 16278511
TI  - Molecular identification of hairtail species (Pisces: Trichiuridae) based on PCR
      RFLP analysis of the mitochondrial 16S rRNA gene.
AB  - A rapid PCR-RFLP analysis was designed to identify 3 closely related species of
      hairtails: Trichiurus lepturus, T. japonicus, and Trichiurus sp. 2, basing on
      partial sequence data (600 bp) of the mitochondrial DNA encoding the 16S
      ribosomal RNA (16S rRNA) gene. Restriction digestion analysis of the unpurified
      PCR products of these 3 species, using EcoRI and VspI endonucleases, generated
      reproducible species-specific restriction patterns showing 2 fragments (250 bp
      and 350 bp) for T. lepturus in EcoRI digestion and 2 fragments (196 bp and 404
      bp) for T. japonicus in VspI digestion, whereas no cleavage was observed for
      Trichiurus sp. 2 in both EcoRI and VspI digestions. The PCR-RFLP technique
      developed in this study proved to be a rapid, reliable and simple method that
      enables easy and accurate identification of these 3 closely related species of
      the genus Trichiurus.

PMID- 16278512
TI  - Model comparison for genetic evaluation of milk yield in crossbred Holsteins in
      the tropics.
AB  - The objective of this study was to compare models for appropriate genetic
      parameter estimation for milk yield (305-day) in crossbred Holsteins in the
      tropics, where only records from crossbred cows were available. Eleven models
      with different effects of contemporary group (CG) at calving (herd-year-season or
      herd-year-month as fixed, and herd-year-month as random), age at calving (as
      linear or quadratic covariates, age-class, and age-class x lactation), and
      dominance were considered. On-farm records from small herds (n < 50) were
      included or excluded to validate the parameter estimates. Average Information
      Restricted Maximum Likelihood (AIREML) and Best Linear Unbiased Prediction (BLUP)
      were used to estimate variance components and breeding values. R-square (R2) and
      standard error of heritability (h2) were used to determine the appropriate model.
      The estimates of heritability from most models ranged from 0.18 to 0.22. CG
      formation of herd-year-month as a random effect slightly lowered the additive
      genetic variance but considerably decreased the permanent environmental variance.
      The model with age-class x lactation gave better R2 than other age adjustments.
      The models including records from smallholders gave similar estimates of
      heritability and a lower standard error than the models excluding them. The
      estimate of dominance variance as a proportion of total variance was close to
      zero. The low ratio of dominance to additive genetic variance suggested that the
      inclusion of dominance effects in the model was unjustified. In conclusion, the
      model including the effects of herd-year-month, age-class x lactation, as well as
      additive genetic, permanent environmental and residual effects, was the most
      appropriate for genetic evaluation in crossbred Holsteins, where records from
      smallholders could be included.

PMID- 16278513
TI  - No incidence of DUMPS carriers in Polish dairy cattle.
AB  - DUMPS (Deficiency of Uridine Monophosphate Synthase) is a hereditary recessive
      disorder in Holstein cattle causing early embryo mortality during its
      implantation in the uterus. The only way to avoid the economic losses is early
      detection of DUMPS carriers. Because American Holstein semen has been intensively
      imported to Poland since 1970, there was a risk that DUMPS could have spread in
      Polish dairy cattle. In our study, 2209 dairy cattle of the Polish Holstein breed
      have been screened by the DNA test. The dominant group was young bulls entering
      the testing program (1171) and proven bulls (781). They represented all sires
      entering Polish breeding programs between 1999 and 2003. Also, 257 sire dams were
      included in the screening program. No DUMPS carrier has been found. Our results
      then indicate that the population of dairy cattle reared in Poland is free from
      DUMPS. Because of the economical significance of the DUMPS mutation and its
      recessive mode of inheritance, attention has to be paid to any case of a bull
      having in his origin any known DUMPS carrier. Such a bull should be tested and if
      positive eliminated from the active population. Also, young bulls (testing bulls)
      should be screened for DUMPS if in their progeny a high incidence of embryo
      mortality is observed and their genealogy cannot exclude their relatedness to any
      DUMPS carriers.

PMID- 16278514
TI  - A novel polymorphism in exon 1 of the porcine myogenin gene.
AB  - Myogenin is a gene belonging to the MyoD family, which codes for the bHLH
      transcription factor playing a key role in myogenesis. It affects the processes
      of differentiation and maturation of myotubes during embryogenesis. Fragments of
      the porcine myogenin coding sequence and promoter region were amplified and
      subjected to MSSCP analysis. T-->C transition recognised by the MaeIII
      restriction enzyme in exon 1 was revealed, which appeared to be a silent mutation
      in the region of the transactivation domain. No other polymorphism was found
      either in the remaining coding sequence or the promoter region.

PMID- 16278515
TI  - Single nucleotide polymorphisms in exon 10 of the chinchilla growth hormone
      receptor (GHR) gene.
AB  - The aim of this study was to detect SNPs in exon 10 of the chinchilla growth
      hormone receptor gene (GHR) by comparative sequencing. Sixty females of the same
      breed (Standard) were analysed. Four new SNPs were identified, which cause 3
      amino acid substitutions in the intracellular domain of the receptor: G/C at
      position 135 bp (in relation to the total sequence of exon 10) (gln/his), CAG/AAA
      at 352 bp and 354 bp (gln/lys), and C/A at 641 bp (thr/asn).

PMID- 16278516
TI  - Significant involvement of chromosome 13q deletions in progression of larynx
      cancer, detected by comparative genomic hybridization.
AB  - Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumours
      with various clinical characteristics. These tumours generally exhibit complex
      karyotypes. Few studies of genomic imbalances have been performed exclusively in
      subgroups of larynx cancer samples at different stages of the disease. In the
      present study, chromosomal gains and losses were investigated in 52 larynx
      tumours, by using comparative genomic hybridization (CGH). The mean number of
      observed alterations was 37.7 per tumour. The most common sites of losses were
      1p, 13q, Xp, and the most common gains were located in 1p, 9q, 16q. The overall
      number of gains was negatively associated with cancer grading. G1 tumours were
      also characterized by a higher frequency of deletions in 13q32 and amplifications
      in 1q23, than tumours in other grades (p < 0.05). The frequency of losses of
      13q22 also positively associated with tumour size. There was no association
      between the frequency of losses in 13q and the presence of lymph node metastases
      at the time of diagnosis. Another statistically significant association was
      observed for gains at 1q22-23 and tumour size (p < 0.01). No statistically
      significant difference in the frequency of most common imbalances was detected
      between primary tumours with lymph node metastases and those without metastases.
      In conclusion, we discovered a significant involvement of 13q deletions in the
      progression of larynx cancer. All the other significant changes observed in the
      present study were reported previously as being important for HNSCC progression.
      It seems that multiple genes are disrupted in the process of neoplastic
      transformation in the larynx, and the networks of events remain to be elucidated.

PMID- 16278517
TI  - Ambiguous genitalia by 9p deletion inherent to a dic(Y;9)(q12;p24).
AB  - We describe here a 3-month-old male infant with brachy-plagyocephaly, short neck,
      widely spaced nipples, mild hypertonia, and ambiguous external genitalia but with
      both testes in the scrotum and no Mullerian derivates. His karyotype was
      45,X,der(Y;9)(q12;p24).ish der(Y;9)(DYZ3+,SRY+,9ptel-) de novo. This patient's
      impaired sex differentiation is consistent with gonadal dysgenesis and compares
      with the male-to-female sex reversal secondary to a partial 9p deletion in spite
      of an intact Yp or SRY locus documented in 24 patients including a sex-reversed
      girl with a (Y;9) dicentric derivative. As for the cytogenetic findings, this
      case represents the second instance of a de novo pseudodicentric (Y;9) chromosome
      with loss of both distal 9p and Yq12 regions, apparent intactness of SRY, and
      consistent or preferential inactivation of the Y centromere. In addition, the
      possible 9p23p-p22 duplication observed in this case evokes the concomitant 9p22
      p21 duplication documented in the previous girl with a (Y;9) derivative. Hence,
      these striking similarities point to a nonrandom Y;9 rearrangement in patients
      with either sex reversal or gonadal dysgenesis. Even if the present
      pseudodicentric derivative had inactivated the Y centromere, the existence of
      some variant cells points to functional dicentricity as it has been documented in
      other Y;autosome dicentric derivatives.

PMID- 16278518
TI  - Additional chromosome in a child as a result of a balanced reciprocal
      translocation t(12;18)(p13;q12) in his mother's karyotype.
AB  - In this case report we present a child with an additional chromosome in the
      karyotype. The karyotypes of the boy and his parents were analyzed by use of a
      conventional banding technique (GTG) and fluorescence in situ hybridization
      (FISH). Probes painting whole chromosomes 12 and 18 were used in FISH.
      Cytogenetic examination of the parents revealed that his mother was carrying
      balanced reciprocal translocation between chromosomes 12 and 18. Her karyotype
      was described as 46,XX,t(12;18)(p13;q12). Father's karyotype was normal,
      described as 46,XY. The boy's karyotype was defined as
      47,XY,+der(18)t(12;18)(p13;q12). The additional chromosome appeared probably due
      to 3:1 meiotic disjunction of the maternal balanced translocation, known as
      tertiary trisomy. The mother displayed a normal phenotype and delivered earlier a
      healthy child. However, the boy with the unbalanced karyotype shows multiple
      congenital abnormalities.

PMID- 16278519
TI  - A modified procedure for quantitative analysis of mtDNA, detecting mtDNA
      depletion.
AB  - Quantitative analysis of mitochondrial DNA (mtDNA) is crucial for proper
      diagnosis of diseases that are caused by or associated with mtDNA depletion.
      However, such a quantitative characterization of mtDNA is not a simple procedure
      and requires several laboratory steps at which potential errors can accumulate.
      Here, we describe a modified procedure for quantitative human mtDNA analysis. The
      procedure is based on using two PCR-amplified, fluorescein-labeled DNA probes,
      complementary to mtDNA (detection probe) and chromosomal 18S rDNA (reference
      probe), both of similar length. Thus, equal amounts of these probes can be used
      and, contrary to previously published procedures, no mtDNA purification (apart
      from total DNA isolation) or 18S rDNA cloning is necessary for probe preparation.
      Two separate hybridizations (each with one probe) are suggested instead of one
      hybridization with both probes; this decreases background signals and enables
      adjustment of the strength of specific signals from both probes, which is useful
      in the subsequent densitometric analysis after superimposing of both pictures.
      Using different DNA amounts for reactions, we have proved that the procedure is
      quantitative in a broad range of sample DNA concentrations. Moreover, we were
      able to detect mtDNA depletion unambiguously in tissue samples from patients
      suffering from diseases caused by dysfunction of mtDNA.

PMID- 16278520
TI  - Development of diabetes with thiazide diuretics: the potassium issue.

PMID- 16278521
TI  - Efficacy of combination therapy for systolic blood pressure in patients with
      severe systolic hypertension: the Systolic Evaluation of Lotrel Efficacy and
      Comparative Therapies (SELECT) study.
AB  - Systolic hypertension is predominant among patients over 50 years of age, is a
      more important cardiovascular risk factor than diastolic blood pressure, and is
      more difficult to control than diastolic blood pressure. Consequently, the
      Seventh Report of the Joint National Committee on Prevention, Detection,
      Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends combination
      therapy as first-line treatment for patients with stage 2 hypertension. In the
      Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) study,
      24-hour ambulatory blood pressure monitoring was used to identify patients with
      systolic hypertension and to determine the impact of 8 weeks of treatment with
      either amlodipine besylate/benazepril HCl 5/20 mg combination therapy (n=149),
      amlodipine besylate 5 mg (n=146), or benazepril HCl 20 mg (n=148). Combination
      therapy was significantly more effective in reducing systolic blood pressure and
      pulse pressure than either monotherapy (p<0.0001). Significantly greater
      percentages of patients in the combination group compared with either monotherapy
      achieved blood pressure control (p<0.0001). Adverse events were low in all three
      treatment arms, with less peripheral edema in the combination group than in the
      amlodipine-treated group. The combination of amlodipine besylate/benazepril HCl
      given to patients with stage 2 systolic hypertension resulted in significantly
      greater reductions in blood pressure and pulse pressure than those seen with
      monotherapy and was at least as well tolerated as the separate components. This
      data supports the recommendation of the JNC 7 for the use of combination therapy
      in patients with stage 2 hypertension.

PMID- 16278522
TI  - Changes in the continuation of antihypertensive drug use after ALLHAT.
AB  - An analysis was performed of the 1-year continued use of various antihypertensive
      agents in a health maintenance organization following the 2002 publication of the
      Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
      (ALLHAT). Computer-stored information was used from the health maintenance
      organization's prescription information system. Only patients newly started on
      antihypertensive medications in 2001 and the calendar year following the ALLHAT
      publication were analyzed. Patients were considered to be persistent with their
      first prescribed antihypertensive drug class if they obtained at least one refill
      for the same class of antihypertensive agents on or within 3 months of the end of
      the 1-year follow-up period. The overall 1-year continuation rate decreased from
      2001 to 2003. However, the continuation of thiazide-type diuretic use after
      ALLHAT (2003) was higher than that before ALLHAT (2001) (p=0.004), whereas the
      continuation rate was lower for all other drug classes. We provide data to
      suggest that evidence from randomized trials is one factor influencing the
      continued use of antihypertensive medication.

PMID- 16278523
TI  - A drug dose model for predicting clinical outcomes in hypertensive coronary
      disease patients.
AB  - To understand the effects of single- and multiple-drug combinations for
      hypertension on the risk of adverse clinical outcomes, the authors analyzed data
      from the International Verapamil SR/Trandolapril Study (INVEST). This trial
      randomized 22,576 hypertensive patients with coronary artery disease to sustained
      release verapamil or to atenolol as initial agents, followed by trandolapril or
      hydrochlorothiazide. Electronically collected prescription data from INVEST
      during 61,835 patient-years were analyzed using a Cox proportional hazards model
      with nine covariates (randomization strategy, four average daily dose terms, two
      ratios measuring the proportion of time the first two drugs in the treatment arm
      were coprescribed, and two interaction terms). Increasing doses of atenolol and
      sustained-release verapamil were associated with decreasing risk of the composite
      primary outcome (death, myocardial infarction, or stroke). Combination therapy
      with two drugs (verapamil/trandolapril or atenolol/hydrochlorothiazide) reduced
      the risk of primary outcome compared with monotherapy (verapamil or atenolol),
      and triple therapy (verapamil/trandolapril/hydrochlorothiazide or
      atenolol/hydrochlorothiazide/trandolapril) further reduced the risk.

PMID- 16278524
TI  - Systemic hypertension among women with uterine leiomyomata: potential final
      common pathways of target end-organ remodeling.
AB  - The uterus and the heart share a common structure and may remodel in a similar
      fashion, albeit temporally distinct. The authors investigated the prevalence of
      systemic hypertension in women with uterine leiomyomata (fibroids) and compared
      the prevalence in women undergoing hysterectomy for other reasons as well as in
      age-matched women from the National Health and Nutrition Examination Survey III
      (NHANES III). A total of 584 women, 205 with leiomyomata in 1999 (group A) and
      379 who underwent hysterectomy for a variety of reasons in 2000 (group B) at
      Advocate Christ Medical Center were included. Presence of leiomyomata was
      confirmed by pathology. Hypertension was defined as blood pressure > or = 140/90
      mm Hg or history of hypertension with or without medication use. The prevalence
      of hypertension in group A and B patients with leiomyomata compared with NHANES
      III overall was 48.6% vs. 24% (p<0.001), in African Americans 55.5% vs. 32.4%
      (p<0.001), and in Caucasians 51.1% vs. 23.3% (p<0.001). Leiomyomata were more
      frequent among hypertensive than normotensive women (57% vs. 27%). Caucasian and
      African-American women with leiomyomata were significantly younger and more
      likely to use hormone replacement therapy than others. Thus there appears to be
      an association between leiomyomata and hypertension, which needs to be explored
      in future prospective trials.

PMID- 16278525
TI  - Pathophysiologic, diagnostic, and therapeutic aspects of the metabolic syndrome.
AB  - The metabolic syndrome, characterized by increases in waist circumference, blood
      pressure, and triglyceride concentrations combined with reduced high-density
      lipoprotein and evidence of glucose intolerance, results from the interaction of
      visceral or central obesity with insulin resistance. This syndrome presents a
      clinical situation of systemic inflammation and increased cardiovascular risk.
      Blood pressure, even if only in the "prehypertensive" range, plays an important
      role in increasing the risk of cardiovascular disease. Recognition and treatment
      of each individual component of the metabolic syndrome is critical in reducing
      cardiovascular risk. Treatment should begin with lifestyle changes, including
      diet, exercise, and weight reduction. Antihypertensive therapy should be directed
      toward reduction of blood pressure to levels as close to optimal (<120/80 mm Hg)
      as feasible, and treatment protocols that do not cause worsening of glucose
      intolerance should be selected. Therapy for dyslipidemia should be directed at
      reducing triglycerides and increasing high-density lipoprotein. Glucose-lowering
      agents may be indicated, and drugs such as metformin and thiazolidinediones,
      which reduce insulin resistance, should form the basis of therapy. Carefully
      chosen therapy will effectively improve cardiovascular outcomes.

PMID- 16278526
TI  - The Hurricane Katrina disaster: focus on the hypertensive patient.

PMID- 16278527
TI  - Pharmacotherapy review: Angiotensin receptor antagonists.
AB  - Angiotensin receptor blockers are one of several drug classes that act by
      interfering with activity of the renin-angiotensin axis. Drugs in this class are
      as effective as angiotensin-converting enzyme inhibitors in the reduction of
      blood pressure in hypertensive patients. Results from a series of outcomes trials
      increasingly support the use of drugs in this class as cardioprotective and
      renoprotective agents in patients with heart failure, diabetic nephropathy, and
      post-myocardial infarction.

PMID- 16278528
TI  - Why don't we use nitrates to treat older hypertensive patients?

PMID- 16278531
TI  - In pursuit of a safe Canadian healthcare system.
AB  - This paper provides evidence that Canada's healthcare system is not as safe as it
      needs to be, and suggests ways to make it safer. Healthcare leaders must
      recognize that patient safety is indistinguishable from the delivery of high
      quality, affordable healthcare, and they must become more knowledgeable about the
      extent of the patient safety problem in Canada. The creation of a Patient Safety
      Board, modelled after Canada's Transportation Safety Board, will provide the
      authority healthcare leaders require to reduce medical errors. Without a national
      Patient Safety Board we cannot efficiently and effectively identify, quantify and
      address medical errors in Canada. This paper also urges healthcare leaders to
      recognize that a fundamental tool in improving patient safety is the electronic
      health record (EHR). Return on investment data for a national EHR strategy are
      presented. The author focuses on three EHR initiatives: outpatient electronic
      prescribing; in-patient computerized physician order entry; and home-based
      diabetes disease management. Potential net savings to Canada from these three EHR
      initiatives alone approach $2 billion annually. We must accelerate our EHR
      investment. Coordinated national EHR initiatives will cost less, save lives and
      prevent harm when compared to the status quo. These initiatives will also provide
      the foundation for transforming our healthcare system and will assist in building
      a better-educated, healthier and therefore more economically competitive nation.

PMID- 16278532
TI  - Hippocrates denied: why Canada has yet to act on the patient safety imperative.
AB  - A review of patient safety literature reveals clear documentation of significant
      patient safety concerns in many countries going back over two decades. However,
      it was not until the publication of the Institute of Medicine's To Err Is Human
      about four years ago that widespread attention was at last drawn to this issue.
      Even with this attention, there has been a very limited response in Canada to the
      well-documented need for action to address preventable errors. After some
      reflection, it is clear that a whole series of factors may be conspiring to slow
      or blunt our response to this issue. This commentary explores these factors and
      endorses strategies for moving forward.

PMID- 16278533
TI  - The electronic health record: a leap forward in patient safety.
AB  - In his review of patient safety issues in the Canadian healthcare system, Dr.
      Matthew Morgan states that "coordinated national EHR initiatives will cost less,
      save lives and prevent harm when compared to the status quo." Canada Health
      Infoway is spearheading this initiative in Canada. Infoway's No. 1 guiding
      principle for investment is that projects undertaken must "enhance the quality of
      patient care, healthcare services and patient safety." They must also support the
      development and adoption of pan-Canadian interoperable EHR solutions. Infoway is
      working in seven major areas to improve electronic access to accurate and timely
      health information in order to reduce errors, facilitate accurate diagnoses and
      speed treatment. These areas include the building blocks of the EHR:
      infostructure, registries, digital imaging systems, and drug and laboratory
      information systems. Infoway is also developing and expanding telehealth networks
      to increase the scope of the Canadian healthcare system. Infoway was recently
      mandated to develop a public health surveillance system for infectious diseases
      to give healthcare providers a tool for tracking and managing disease outbreaks
      in the Canadian population. These systems will improve safety, quality,
      accessibility, cost-efficiency and the sustainability of the healthcare system.
      Patient safety is a cornerstone of Infoway's activities.

PMID- 16278534
TI  - Patient safety: is the evidence strong enough that information technology can
      help?
AB  - It is not difficult to prepare a commentary on Dr. Morgan's invited essay "In
      Pursuit of a Safe Canadian Healthcare System" if one agrees with almost
      everything he reveals and postulates. When a respected young practising physician
      candidly and forcibly makes a case for the need for significant healthcare system
      reform, one must sit up and take notice. If nothing else, his statement
      "outpatient medical errors are the bread and butter of internal medicine hospital
      admissions" should cause us to be deeply concerned. Dr. Morgan pleads for a
      number of reforms, such as the creation of a Patient Safety Board akin to Canada
      s Transportation Safety Board, the demonstration of an ROI for the electronic
      health record, the introduction of computerized physician order entry, and a
      number of other suggestions. Due to limitations of time and space, we will react
      to only a few of his views, mildly disagreeing with some while strongly
      reinforcing others.

PMID- 16278535
TI  - Grasping the opportunity to improve the safety of care.
AB  - Clearly a wakeup call for the healthcare industry, the IOM report of 2000 To Err
      Is Human now appears to have been a sentinel event, at least in the United States
      (Institute of Medicine 1999). Given that the practice of medicine in the United
      States is, in many ways, very similar to that in Canada--for example, our
      physician trainees are educated and evaluated using similar models--it is
      unfortunate that the IOM report was not also a wakeup call for Canada. Four years
      have passed, and apparently Canadians have only recently woke up to front-page
      newspaper headlines that point out that Canadians, like Americans, are being
      harmed and killed as a result of medical errors.

PMID- 16278536
TI  - The impact of the electronic health record on patient safety: an Alberta
      perspective.
AB  - Alberta is at the leading edge in developing its electronic health record (EHR ),
      a provincial initiative to provide healthcare providers with immediate access to
      a patient's medication history and laboratory test results, regardless of where
      they are in the province, or where the patient's drugs or other treatments were
      ordered. The Alberta EHR was launched in October 2003. So far 6,000 healthcare
      providers have voluntarily signed on to use it, and benefits to patient safety
      have been reported. The EHR is an important part of healthcare renewal that is
      required to improve patient safety; however, it must not be viewed as a stand
      alone cure-all solution to Canada's patient safety challenge. The EHR will only
      reach its full potential if it is part of an integrated approach to health
      renewal that stresses consistency of healthcare, practice and information
      standards, and consistency and standardization of healthcare data. Without a
      sector-wide EHR like Alberta's, the proliferation of computerized electronic
      medical records (EMRs) in hospitals, clinics and pharmacies might create "islands
      of information" that are not widely compatible. A national EHR approach must
      acknowledge the importance of improving broadly accepted practice standards and
      data consistency in order to reduce the islands of information and protect
      patients from medical errors as they move between them.

PMID- 16278537
TI  - Improving patient safety through computerized drug management: the devil is in
      the details.
AB  - Electronic prescribing and computerized drug management can improve the safety,
      quality and cost-effectiveness of prescribing. However, if the problems that lead
      to avoidable adverse events are not addressed by information technology, there is
      a risk of making considerable investment without the expected return of error
      reduction and improved patient safety. Improving the safety of prescribing is
      particularly important in ambulatory care, where most drugs are prescribed. To
      improve patient safety, IT solutions should be developed that provide: (1) access
      to the list of all currently active drugs, (2) alerts for relevant prescribing
      problems (therapeutic duplication, excess dose, dose adjustment for weight
      (children, elderly) and renal impairment, drug-disease, drug-drug, drug-age and
      drug-allergy contraindications), (3) the capacity to electronically submit
      medication stop orders to the dispensing pharmacy and (4) integration of
      electronic prescriptions (e-rx) into pharmacy software to avoid transcription
      errors. To improve quality of prescribing, IT solutions should be capable of
      providing physicians with reminders and alerts for evidence-based preventive care
      and disease management based on patient-specific drug, disease, therapeutic
      intent and other relevant clinical information. To improve the cost-effectiveness
      of prescribing, IT solutions should be developed to provide the cost of
      medication at the time the prescription is written, and evidence-based alerts for
      drugs of choice recommendations when appropriate.

PMID- 16278538
TI  - Envisioning safer healthcare.
AB  - Morgan provides an action plan for safer Canadian healthcare and argues that
      needed, fundamentally safer healthcare requires commitment to change from
      policymakers, healthcare leaders and practitioners. He posits that safer
      healthcare in Canada can be achieved through information technology (IT) and a
      national patient safety investigative agency.

PMID- 16278539
TI  - Next steps for patient safety in Canadian healthcare.
AB  - Morgan outlines some important elements necessary for improving patient safety in
      Canadian healthcare. But these steps are likely to require considerable time and
      resources and may be difficult to implement. In the light of the evidence of
      adverse events in Canadian hospitals, all Canadian healthcare organizations need
      to begin to measure the numbers and types of adverse events experienced by their
      patients and clients. Staff need to learn new skills for investigating and
      improving care. A variety of tools and resources are available for these tasks.
      Leadership both in senior management and on the front lines must learn to shift
      the focus from blaming individuals to improving systems of care. Leaders must
      also acknowledge that most healthcare organizations have failed to gather the
      necessary information on adverse events, and they must invest in building
      knowledge and implementing practices that reduce the current levels of injury.

PMID- 16278541
TI  - Return to play: the sideline dilemma.

PMID- 16278542
TI  - Sideline documentation and its role in return to sport.
AB  - OBJECTIVE: To determine common sideline practices for the management of clinical
      information in the collegiate setting and review available literature on sideline
      documentation. DATA SOURCES: A survey was distributed to member schools of the
      Atlantic Coast Conference (ACC) to elicit the individual school practices with
      regard to injury evaluation, medication dispensation, extent of medical record
      availability, and means and timing of documentation. Articles were retrieved from
      Pubmed and SportDiscus searches for combinations of terms sports injuries,
      athletic injuries, return to play, documentation, medical record, injury report,
      injury card, and injury tracking for items relevant to sideline documentation
      methods for return to play decision making. RESULTS: We obtained responses from
      100% of member schools. One hundred percent of ACC member schools dispense
      prescription medication following injury evaluation on the sideline. Four of 11
      schools do not perform some elemental documentation at that time. Four of 11 ACC
      schools use some form of electronic medical record for injury documentation. Most
      schools have access to elemental medical information (such as allergy and medical
      conditions) on the sideline. A literature search yielded several references to
      concussion and injury tracking; however, no systematic reports examining sideline
      documentation systems were obtained. Two articles utilizing card-based systems
      for injury tracking in the collegiate setting were retrieved. CONCLUSIONS: On
      field documentation of return to play decision making has not been widely
      discussed or systematically studied. In the ACC, most institutions record
      clinically relevant athletic injury data on-site at the time of evaluation and
      later prepare a full note describing the evaluation and return to play decisions.
      We discuss a laminated card-based and a handheld computer-based system as 2
      methods for efficient documentation of sideline treatment and return to play
      decisions. Commercial products and sideline information management and data
      collection are also discussed.

PMID- 16278543
TI  - Determination of safe return to play for athletes recovering from infectious
      mononucleosis: a review of the literature.
AB  - OBJECTIVE: Infectious mononucleosis is an acute self-limited disorder diagnosed
      by clinical and hematologic measures. This paper reviews the literature regarding
      the decision-making process for return to play in individuals at risk for
      complications due to infectious mononucleosis. DATA SOURCES: Computerized
      literature search identified articles using the keywords infectious
      mononucleosis, athlete, injury, exercise, spleen rupture, and spleen radiography.
      Symptoms, physical examination, hematological markers, and radiographic
      evaluation were considered. CONCLUSIONS: No strong evidence-based information
      supports use of a single parameter to predict the safe return to sports
      participation. Current consensus supports that athletes be afebrile, well
      hydrated, and asymptomatic with no palpable liver or spleen. Clinical judgment
      incorporating these criteria 1 month after diagnosis has been suggested as a safe
      predictor for gradual return to competition. These conditions for return to play
      do not guarantee that the spleen has returned to normal size and compliance, or
      that the risk of spleen rupture has returned to baseline. For those athletes
      participating in contact sports who wish to return to sports in an earlier time
      frame, or those with an equivocal examination, radiographic modalities may be
      used to help determine liver and spleen size. Further studies are required to
      support this practice.

PMID- 16278544
TI  - Evaluating cardiac symptoms in the athlete: is it safe to play?
AB  - OBJECTIVE: Concern regarding the risk of sudden unexpected cardiac death has
      fueled interest in athletes who experience chest pain, syncope, or palpitations
      during training and competition. This review examines the etiology and evaluation
      of these symptoms in young athletes. DATA SOURCES/SYNTHESIS: Previously published
      reports that have provided a base of expert opinion were examined to define the
      optimal means of assessment before returning athletes to play. RESULTS: A well
      defined differential diagnosis must be considered to rule out heart disease and
      define noncardiac causes of these symptoms. CONCLUSIONS: Athletes who experience
      symptoms such as chest pain, syncope, and palpitations during competition and
      training can be safely returned to play only after the evaluation is completed.

PMID- 16278545
TI  - Return to play following exercise-induced bronchoconstriction.
AB  - OBJECTIVE: To review evidence-based support for return to play criteria following
      acute exercise-induced bronchoconstriction. DATA SOURCES: Electronic databases
      Ovid Medline and PubMed were searched for papers relating to exercise related
      asthma and bronchoconstriction and return to play criteria. Additional references
      from the bibliographies of retrieved articles were also reviewed. DATA SYNTHESIS:
      There is clear evidence that exercise-induced airways narrowing is increasing in
      prevalence among athletes from school children to Olympians to professionals, yet
      there have been no studies specifically addressing return to play criteria.
      Although deaths from exercise associated bronchoconstriction were previously
      thought to be rare, recent reports of such deaths call for increased awareness by
      physicians, athletic trainers, and coaches of the potential fatal consequences of
      unrecognized episodes or of inadequate treatment. CONCLUSIONS: No agreed-upon
      protocol for safe return to play following an acute episode of exercise induced
      bronchoconstriction has been published. A specific detailed protocol for return
      to play would assist physicians and other heath professionals to determine with
      greater confidence that an athlete is fully recovered and can safely return to
      play.

PMID- 16278546
TI  - Return to play after concussion: principles and practice.
AB  - OBJECTIVE: The sport medicine team is increasingly being asked to manage
      concussed athletes and to provide written clearance for return to play
      postconcussion, making it critical to have a good understanding of concussion
      recognition, assessment, and management. DATA SOURCES/SYNTHESIS: A handy way to
      think of concussion management is the four Rs: recognition, response,
      rehabilitation, and return. RESULTS: Athletes, coaches, parents, therapists, and
      physicians need a thorough understanding of concussion signs and symptoms. An
      athlete suspected of having sustained a concussion should be removed from the
      game or practice and assessed by a member of the sideline medical team. All
      athletes who sustain a concussion should be evaluated by a medical doctor.
      Rehabilitation has similarities to but also differs from the traditional
      orthopedic model in that the first step is rest, both physical and cognitive.
      Once asymptomatic at rest, a step-wise return to activity is undertaken.
      CONCLUSIONS: This protocol has been adapted for various sports. It may be used
      for children, although it is prudent to be more conservative and to progress more
      slowly than in an older age group.

PMID- 16278547
TI  - Returning to play: the mind does matter.
AB  - OBJECTIVE: The purpose of this article was to provide a brief historical
      perspective of the psychological factors that affect the potential for athletic
      injury, the psychological variables that affect recovery from injury, and the
      increasing pressure athletes face to return to play as soon as possible following
      an injury. DATA SOURCES/METHODS: A literature search was conducted using
      SportDiscus with keywords athlete, injury, sport psychology, and return to play.
      Further support for the literature cited and conclusions comes from more than 16
      years of collegial consultations and direct clinical experience with multiple
      collegiate, Olympic, and professional sport organizations. RESULTS: Although the
      primary body of research regarding the psychological factors affecting sport
      injury and return to play is found in studies conducted in the 1980s, more recent
      research continues to support many of the original findings. Additionally, the
      applied experience of a full-time licensed and practicing sport psychologist is
      consistent with the early and subsequent research. CONCLUSIONS: Research,
      supported by applied experience, has resulted in the development of a set of
      causative psychological factors that increase the likelihood of sport injury,
      increase the potential recovery time from injury, and have thus far stood the
      test of time. One factor, however, that has changed over the years is the
      increasing pressure that elite athletes experience in returning to play much more
      quickly following an injury. Awareness of this increasing pressure is an
      important consideration for health care providers and sport organizations to
      ensure that athletes return medically and psychologically ready to play.

PMID- 16278548
TI  - Return to play following muscle strains.
AB  - OBJECTIVE: To assess return to play strategies following muscle strains with the
      desired outcomes of decreased competition play lost and minimized risk for
      recurrent injury. METHODS: Literature review of previous studies that examine
      return to play criteria for the commonly seen muscle strain injuries in sport.
      RESULTS: There have been no studies directly comparing different return to play
      approaches. Studies have instead concentrated on recurrence risk factors and
      prognosis assessment, particularly for hamstring injuries. There is some
      literature support for risk factors for recurrence such as persisting strength
      deficits, larger injuries seen on diagnostic imaging, players in high-risk
      positions or sports, inability to complete functional tasks without pain, and
      strains of specific high-risk muscles (biceps femoris, central tendon of rectus
      femoris, medial head of gastrocnemius, adductor longus or magnus). CONCLUSIONS:
      There are no consensus guidelines or agreed-upon criteria for safe return to
      sport following muscle strains that completely eliminate the risk for recurrence
      and maximize performance. At this time, it may be a sensible strategy to allow
      earlier return to play in team sports and accept a low to moderate injury
      recurrence rate. Improved prognostic assessment of muscle strains with injury
      identification (MRI) and injury assessment (isokinetic testing) may be assist
      practitioners to lower, but not eliminate, recurrent injuries.

PMID- 16278549
TI  - Management and return to play of stress fractures.
AB  - OBJECTIVE: The purpose of this article is to provide the clinician an
      evidence/experience-based algorithm for the management of stress fractures. DATA
      SOURCES: Medline search of peer reviewed publications regarding stress fracture
      etiology, classification, treatment, and natural history. DATA SYNTHESIS/METHODS:
      The algorithm was developed from a review of retrospective case series, a few
      evidence-based papers, and the clinical experience of 4 sports medicine team
      physicians with a combined experience of over 40 years in the care of athletes at
      the college and professional level. The literature is almost entirely case series
      without control groups; therefore, clinical consensus is included as the next
      best guide to treatment. RESULTS: The emphasis of this article is to provide a
      clear and simple approach to the management of these fractures by classifying
      them as either high-risk or low-risk. This separation into 2 groups is based on
      the biomechanical environment and natural history of the fracture. High-risk
      stress fractures occur in the superolateral femoral neck, anterior tibial shaft,
      tarsal navicular, proximal fifth metatarsal, and talar neck. Low-risk stress
      fractures occur in the lateral malleolus, calcaneus, 2nd through 4th metatarsals,
      and the femoral shaft. CONCLUSIONS: The undertreatment of high-risk stress
      fractures can lead to catastrophic bone failure and/or prolonged loss of playing
      time. Overtreatment of low-risk stress fractures can result in unnecessary
      deconditioning and unneeded loss of playing time. We propose that the use of the
      simple and clinically relevant algorithm will help guide appropriate management
      and return to play decision-making as well as encourage future prospective
      research.

PMID- 16278550
TI  - Return to play issues in upper extremity injuries.
AB  - OBJECTIVE: The purpose of this paper is to outline general treatment and return
      to play (RTP) strategies as they pertain to athletes with various upper extremity
      injuries. It is not intended to be a comprehensive review of these injuries. DATA
      SOURCES/SYNTHESIS: A review of the literature plus expert opinion served as the
      basis for recommendations made regarding management strategies for returning the
      athlete to play after upper extremity injury. A Medline search was performed
      using the following key words: upper extremity injury, return to play,
      glenohumeral dislocation, acromioclavicular joint sprains, elbow dislocation,
      scaphoid fracture, metacarpal fracture, finger dislocation, tendon injury, hand,
      mallet finger, and jersey finger. These and other related terms were crossed
      using the Medline database from 1966 to 2005. RESULTS: Review of book chapters,
      articles generated from the Medline search, and expert opinion led to the
      recommendations that are presented here. There is general agreement regarding the
      treatment of many of the injuries discussed, but controversies do exist. RTP
      guidelines are largely dependent on the severity of initial injury, rates of
      healing, and return of strength. CONCLUSIONS: Each athlete with a particular
      injury to the upper extremity needs to be approached as an individual as no
      single set of treatment or RTP guidelines applies to all injuries or all
      individuals. Factors such as age, injury severity, hand dominance, type of sport
      participation, method of treatment, and chronicity of injury are among the many
      issues that must be considered when developing a treatment and RTP strategy for a
      particular athlete.

PMID- 16278552
TI  - Return to play--a personal perspective.

PMID- 16278551
TI  - A review of spine injuries and return to play.
AB  - OBJECTIVE: To review the literature for evidence that pertains to return to play
      and spine injuries, including cervical spinal stenosis, congenital and
      developmental abnormalities of the cervical spine, stingers, herniated nucleus
      pulposus, and spondylolysis/spondylolisthesis. DATA SOURCES: Electronic
      databases, Pubmed (1966-2005) and Sport Discus (1975-2005), were searched for
      pertinent literature. Also, additional articles were reviewed from
      bibliographies. DATA SYNTHESIS/METHODS: Summation of literature is given. No
      formal statistical analysis is presented. RESULTS: Even though the problems
      addressed in this paper can be serious, the literature is lacking evidence for
      guidance in return to play. The majority of the literature presented is expert
      opinion. CONCLUSIONS: Cervical spinal stenosis continues to be controversial,
      with different experts giving different definitions and return to play
      recommendations. Authors discuss functional cervical spinal stenosis seen on MRI
      and how this can lead to permanent sequelae. In regard to stingers, herniated
      nucleus pulposus, and spondylolysis/spondylolisthesis, there are differing
      opinions on evaluation and treatment. These conditions have less disagreement
      with regard to return to play. Most experts agree that with these problems or any
      other problem in sports medicine, an athlete needs to be symptom-free and have
      full active range of motion with near to full strength, even though there is a
      lack of research evidence in the literature.

PMID- 16278553
TI  - Accelerated rehabilitation after anterior cruciate ligament reconstruction.

PMID- 16278554
TI  - Fitness and physical activity as predictors of mortality in unhealthy men.

PMID- 16278556
TI  - Does wearing a helmet affect the risk of head and neck injuries in snow sports?

PMID- 16278555
TI  - Body mass index, physical activity, and mortality in women.

PMID- 16278558
TI  - Energy expenditure in burns: let's measure something else.

PMID- 16278560
TI  - Close relative intermingled skin allograft and autograft use in the treatment of
      major burns in adults and children.
AB  - Major burns still continue to pose problems of inadequate auto skin closure.
      Patients suffering severe burns lack adequate skin graft donor site. We present
      the results of 17 major adult and pediatric burns that we applied close relative
      intermingled skin allograft and autograft in the course of treatment. The extent
      of burn injury ranged from 40%-70% total body surface are (TBSA). Seven patients
      survived and 10 patients died. Mean percent TBSA of the dead and surviving
      patients were 55.5 +/- 11.16 (range, 40-70) and 55.0 +/- 4.08 (range, 50-60)
      respectively. Mean age of the dead and surviving patients were 16.1 +/- 13.77
      (range, 2-42) and 11.1 +/- 6.74 (range, 2-21), respectively. We present a safe
      and satisfactory means of effective alternative treatment to resurface major
      burns in case of limited auto skin graft donor site without exposure to bacteria,
      human immunodeficiency virus, and hepatitis virus when keratinocyte culture
      facilities and skin banks are not available.

PMID- 16278559
TI  - Comparison of measured resting energy expenditure versus predictive equations in
      pediatric burn patients.
AB  - Many equations have been developed to estimate resting energy expenditure (REE)
      in thermally injured patients. A consensus has not been reached on the accuracy
      of these equations in children. The purpose of our study was to compare three
      predictive equations: Harris Benedict x 2 multiplier (HB x 2), Mayes (MG), and
      the WorId Health Organization x 2 multiplier (WHO x 2) with measured resting
      energy expenditure x I.3 multiplier (MREE x 1.3) in pediatric burn patients. MREE
      was measured by open-circuit indirect calorimetry in 10 burned children (6 boys,
      4 girls) aged 2 to 10 years with TBSA burn ranges from 35% to 97%. MREE x 1.3 was
      compared with values obtained by HB x 2, MG, and WHO x 2 predictive equations.
      When comparing MREE x 1.3 with all three equations, significant differences were
      found when compared with HB x 2 and MG, but there were no significant difference
      between MREE x 1.3 vs WHO x 2. The HB x 2 and MG equations overpredicted MREE x
      1.3 by 29% and 19%, respectively. Many predictive equations have been developed
      to predict energy expenditure in burns, but their accuracy in predicting MREE x
      1.3 is variable. A larger study comparing/contrasting predictive equations and
      resting energy expenditure measured by indirect calorimetry is needed to improve
      the prediction of energy needs in burned children.

PMID- 16278561
TI  - Defining the ratio of outcomes to resources for triage of burn patients in mass
      casualties.
AB  - Management of a mass casualty involving burn patients that overwhelms local
      resources will likely require a triage process in which limited resources are
      devoted to the patients with the highest likelihood of survival. No objective
      criteria exist which define how patients could be categorized in such a
      situation. A table that classifies patients according to their anticipated
      survival from burn injury, and the resources required to achieve that survival,
      is presented here. The limitations and restrictions of applying such a guideline
      are discussed in detail.

PMID- 16278562
TI  - The Versajet water dissector: a new tool for tangential excision.
AB  - Goulian and Watson knives work well for tangential burn excision on large flat
      areas. They do not work well in small areas and in areas with a three-dimensional
      structure. The Versajet Hydrosurgery System (Smith and Nephew, Key Largo, FL) is
      a new waterjet-powered surgical tool designed for wound excision. The small size
      of the cutting nozzle and the ability to easily maneuver the water dissector into
      small spaces makes it a potentially useful tool for excision of burns of the
      eyelids, digits and web spaces. The Versajet Hydrosurgery System contains a power
      console that propels saline through a handheld cutting device. This stream of
      pressurized saline functions as a knife. We have used the Versajet for burn
      excision in 44 patients. Although there is a learning curve for both surgeons
      using and operating room staff setting up the device, the Versajet provides a
      relatively facile method for excision of challenging aesthetic and functional
      areas.

PMID- 16278563
TI  - Bacteriological profile and antibiotic resistance: comparison of findings in a
      burn intensive care unit, other intensive care units, and the hospital services
      unit of a single center.
AB  - The purpose of the study was to define the bacteriological profile and antibiotic
      resistance patterns of a burn intensive care unit (ICU) and to compare them with
      the patterns from three other hospital areas in the same center (ie,
      cardiovascular-coronary ICU, a general ICU, and the hospital service unit).
      Bacterial isolates were collected prospectively from the burned patients and the
      patients from the other hospital areas between May 2001 and November 2003. In the
      burn ICU, Pseudomonas aeruginosa was the isolated pathogen most frequently
      (40.4%), followed by Staphylococcus aureus (29.3%) and Acinetobacter spp. (9.8%).
      S. aureus was the most common isolated pathogen in other hospital areas. The
      agents that were most effective against P. aeruginosa in the burn ICU were
      piperacillin/tazobactam and sulbactam/cefoperazon. We observed higher
      antimicrobial resistance in burn ICU than in the other hospital areas studied. In
      conclusion, bacteriological profile and antibiotic resistance patterns of
      patients in the burn ICU are significantly different from those in other ICUs and
      hospital units at our center. This knowledge is crucial for early treatment of
      infections in burned patients.

PMID- 16278564
TI  - Smoking, substance abuse, psychiatric history, and burns: trends in adult
      patients.
AB  - Keeping in mind the historical importance of the associations among smoking,
      substance abuse, psychiatric history, and burns, we collected the relevant data
      as part of a larger research project. A retrospective casenote review was
      conducted using 1981, 1991, and 2001 as reference years to identify the trends in
      acute adult admissions. In keeping with the increase in the total number of
      patients, burns victims who were smokers increased in numbers. The percentage
      increased in 2001 from other reference years, but it was not statistically
      significant. The results of our study also show no significant increase in trends
      as far as burns causation and alcohol/psychiatric history/drug dependence is
      concerned, but the prevalence of these conditions in burns patients has remained
      persistently high compared with the general population in the past 20 years.

PMID- 16278565
TI  - An unusual cause of septicemia and death in a burn patient: discussion and
      review.
AB  - Sepsis remains a common source of morbidity and mortality for seriously burned
      patients. Sources of sepsis are varied, although some are dramatically more
      common than others. Rarely, the burn surgeon may be confronted with an infectious
      source that remains unelucidated until postmortem examination. This case report
      describes the hospital course and subsequent death of a severely burned patient
      with sepsis, the source of which was only discovered on postmortem examination by
      our county medical examiner.

PMID- 16278566
TI  - An analysis of occupational burn injuries in Rhode Island: workers' compensation
      claims, 1998 to 2002.
AB  - Occupational burns have been determined to be a serious public health concern.
      The analysis of workplace risks and risk factors associated with burns are
      critical to developing effective interventions in the future. In this study, we
      examined accepted Rhode Island workers' compensation claims (n = 5619) from 1998
      to 2002 to assess the rates and risks of occupational burns. We used employment
      data from the Department of Labor's Current Population Survey (CPS) to estimate
      claim rates and shift analyses. The overall burn rate was estimated to be 24.3
      per 10,000 workers. The claim rate for workers younger than 25 years of age was
      almost double that for all other age groups. The average per-claim disability
      duration for claims requiring indemnity was 167.9 days, and average annual total
      cost of claims was dollar 1,010,166. The highest claim rate identified was for
      workers in food service occupations and an increased risk was found for chemical
      burns among evening and night-shift workers. Increased interventions are needed
      to reduce occupational burns in work settings. Particular diligence should be
      should address occupational burn hazards in restaurant establishments, and
      preventative should be measures aimed at young employees and late-shift workers.

PMID- 16278567
TI  - Ginkgo biloba extract improves oxidative organ damage in a rat model of thermal
      trauma.
AB  - This study was designed to determine the possible protective effect of Ginkgo
      biloba extract (EGb) against oxidative organ damage distant from the original
      burn wound. Under brief ether anesthesia, the shaved dorsum of the rats was
      exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath
      for 10 seconds. EGb (50 mg/kg/day) or saline was administered intraperitoneally
      immediately and at 12 hours after the burn injury. Rats were decapitated 24 hours
      after burn injury and tissue samples from the liver and kidney were taken for the
      determination of malondialdehyde (MDA) and glutathione (GSH) levels,
      myeloperoxidase (MPO) activity, and collagen contents. Formation of reactive
      oxygen species in the tissue samples was monitored by the chemiluminescence
      technique. Tissues also were examined microscopically. Blood urea nitrogen,
      creatinine, alanine aminotransferase, and aspartate aminotransferase levels and
      tumor necrosis factor- and lactate dehydrogenase activity were assayed in serum
      samples. Severe skin scald injury (30% TBSA) caused a significant decrease in GSH
      levels and significant increases in MDA levels, MPO activity, and collagen
      content of hepatic and renal tissues. Treatment of rats with EGb significantly
      increased the GSH level and decreased the MDA level, MPO activity, and collagen
      contents. Similarly, serum alanine aminotransferase, aspartate aminotransferase,
      and blood urea nitrogen levels, as well as lactate dehydrogenase and tumor
      necrosis factor-, were increased in the burn group as compared with the control
      group. However, treatment with EGb reversed all these biochemical indices, as
      well as histopathological alterations that were induced by thermal trauma. Our
      results show that thermal trauma-induced oxidative damage in hepatic and renal
      tissues is protected by the administration of EGb, with its antioxidant effects.
      Therefore, its therapeutic role as a "tissue injury-limiting agent" must be
      further elucidated in oxidant-induced tissue damage.

PMID- 16278569
TI  - Patients with epilepsy: a high-risk population prone to severe burns as a
      consequence of seizures while showering.
AB  - We document the severe burns sustained by three patients with epilepsy who
      suffered seizures while showering. On the basis of the circumstances of these
      accidents, we suggest preventative measures to help other patients with epilepsy
      avoid similar burn injuries. Patient data collected from January 1987 to May 2004
      by the Burn Unit of the Department of Plastic Surgery, University of Aachen,
      Germany, were reviewed. Three patients with epileptic disorders were found who
      suffered severe burn injuries caused by seizures that occurred while showering.
      Scald location and depth was assessed. Three patients (two women, one man)
      sustained extensive scald injuries after epileptic seizures while showering. Burn
      extent ranged from 20% to 35% TBSA. Scalds primarily affected the trunk, legs,
      arms, and buttocks. Two of the three patients used showers with levers for
      controlling water temperature. Safety devices for limiting water temperature were
      absent. All patients used shower cubicles. Patients with epilepsy may sustain
      serious burns, typically affecting the trunk, legs, arms, and buttocks, when a
      seizure occurs while showering. We suggest that individuals with epilepsy use
      showers designed with pirouetting taps, rather than levers, to regulate water
      temperature. Pirouetting taps are less likely to be shifted out of position
      during a seizure. We also recommend that epileptic patients have safety devices
      installed in their water heaters that limit maximum water temperature. Such
      safety devices prevent scald injury. And, finally, we suggest that people with
      comparable disorders generally avoid using shower cubicles. Instead, showers with
      curtains should be used, which may allow occupants to escape from dangerously hot
      shower water more easily.

PMID- 16278570
TI  - The Functional Independence Measure (FIM) and functional outcomes after a new
      approach to axillary burns.

PMID- 16278571
TI  - Impact of an inpatient rehabilitation facility on functional outcome and length
      of stay of burn survivors.
AB  - This study reviewed the use of an inpatient rehabilitation unit for burn
      survivors. We hypothesized that adult burn patients admitted earlier to inpatient
      rehabilitation have an equal or better functional outcome than those remaining in
      acute burn center for rehabilitation care. Functional Independence Measure (FIM)
      data were prospectively collected on our burn center admissions dating January
      2002 to August 2003. National rehabilitation data were acquired from eRehabData
      and burn literature. A total of 217 adult patients survived until hospital
      discharge, with 21 (9.7%) discharged to inpatient rehabilitation (REHAB). REHAB
      had larger burn injuries, more inhalation injuries, higher incidence hand/foot
      burns, and longer length of stay (LOS). REHAB had lower FIM upon rehabilitation
      facility admission than national averages but greater FIM improvement during
      comparable rehabilitation LOS. Although our earlier rehabilitation admission
      strategy results in more frequent rehabilitation unit referrals, patients had
      shorter burn center LOS and greater FIM improvement compared with limited
      national burn patient functional outcome data currently available.

PMID- 16278572
TI  - Axillary burns: extended grafting and early splinting prevents contractures.
AB  - The development of contractures is a common complication after burn injuries.
      Axillary burns often result in limited abduction of the arm and present a major
      hindrance in rehabilitation. To prevent axillary contractures after burn injury,
      we perform a special grafting technique. In this study we treated 17 patients
      with 23 axillary burns using this technique. Patients were splinted early, and an
      intensive physiotherapy program was started 5 days after splinting. After 12
      months, the mean abduction of the successfully treated axillary burns was 152
      degrees. A secondary reconstruction was needed in only 5 of the 23 treated
      axillary burns. For the treatment of axillary burns, we recommend the described
      grafting technique in combination with early splinting and intensive
      physiotherapy.

PMID- 16278573
TI  - Celebrating progress in psychosocial rehabilitation: empirically validating the
      efficacy of social skills training and body image assessment for burn survivors.

PMID- 16278574
TI  - Efficacy of a short-term, intensive social skills training program for burned
      adolescents.
AB  - This study examined the efficacy of an intensive, short-term social skills
      training program in improving the psychosocial adjustment of burned adolescents.
      Sixty-four adolescents who had suffered a burn injury 2 years previously or
      longer and who were identified as having psychosocial difficulties (elevated
      behavioral problems and/or diminished competence) were assigned randomly to
      receive the treatment intervention or to serve as controls (32 in each group).
      The intervention was a social skills training curriculum provided in a small
      group residential format. Didactic and experiential techniques were used in a
      schedule of activities during a 4-day period. One year after the training
      program, the group who had received the treatment showed significantly more
      improvement than did the control group. The program appears to offer advantages
      to a sizeable group of pediatric burn survivors and indicates the need for
      further study of interventions to enhance psychosocial competence in the
      development of pediatric burn survivors.

PMID- 16278577
TI  - More on directed kidney donation by altruistic living strangers: a response to
      Dr. Hilhorst and his colleagues.

PMID- 16278579
TI  - Exclusive characteristics of graft survival and risk factors in recipients with
      immunoglobulin A nephropathy: a retrospective analysis of registry data.
AB  - BACKGROUND: Some studies have claimed that patients with immunoglobulin A (IgA)
      nephropathy have better graft survival than other renal graft recipients, whereas
      others have rejected this statement. We have addressed this paradox in the
      present study. METHODS: In all, 1,207 patients with IgA nephropathy who received
      a primary cadaveric renal graft from 1990 to 2002 were identified in the
      Eurotransplant database. For comparison, we analyzed 7,935 patients with
      nonglomerular diseases. Death-censored graft survival was calculated using Kaplan
      Meier estimates and a multivariable Cox regression analysis was used for risk
      calculations. RESULTS: Death-censored graft survival was superior in patients
      with IgA nephropathy in the first period after transplantation. After 3 years
      posttransplant, however, there was an accelerated decline in graft survival in
      recipients with IgA nephropathy. The fully adjusted risk of graft loss in the
      first year was increased by 40% in the control group compared to IgA nephropathy
      (hazard ratio [HR] 1.40, 95% CI 1.12-1.75), whereas the risk was significantly
      lower in the control group after the first year posttransplant (HR 0.75, 95% CI
      0.63-0.88). Cold ischemia time, immunization and HLA-DR mismatch were risk
      factors for graft loss in the control group but not for IgA nephropathy, whereas
      HLA-AB mismatch was an independent risk factor, exclusively for the IgA
      nephropathy group. CONCLUSIONS: Recipients with IgA nephropathy have better 1
      year graft survival, presumably due to favorable immunological behavior. This
      benefit was however abolished in the long-term by increased graft loss with time.
      Studies are needed to explain the difference in graft survival and the reason why
      different risk factors are involved in graft failure.

PMID- 16278578
TI  - Glucose stimulation of cytochrome C reduction and oxygen consumption as
      assessment of human islet quality.
AB  - BACKGROUND: An in vitro method to assess human islets could prevent
      transplantation of nonviable islets and facilitate the optimization of islet
      preparation. We hypothesize that glucose-stimulated cytochrome c reduction and
      oxygen consumption by human islets can be used as predictors of transplant
      success. METHODS: Isolated human islets were obtained from research-grade
      pancreata. Using a previously developed islet flow culture system, the response
      of cytochrome c reduction and oxygen consumption to glucose was compared to the
      ability of islets transplanted into nondiabetic NOD-SCID mice to secrete C
      peptide in response to a glucose tolerance test conducted 7 days following
      transplant (n=10). RESULTS: In vitro responses by human islets were qualitatively
      similar to those seen in rat islets: glucose increased both oxygen consumption
      and cytochrome c reduction. However, the responses were smaller in magnitude and
      quite variable. Scatter plots of C-peptide and quantiles for ln(C-peptide)
      indicated that 12 ng/ml could be used as threshold of transplant success with
      which to evaluate the diagnostic potential of cytochrome c and oxygen
      consumption. Data was analyzed by generating receiver operating curves and the
      area under the curve was 0.889 (95% CI: 0.645-1.000) and 0.738 (95% CI: 0.413
      1.000) for cytochrome c reduction and oxygen consumption respectively (1
      indicates absolute predictive capability and 0.5 indicates no predictive
      capability). CONCLUSIONS: The detection of glucose-stimulated cytochrome c
      reduction and oxygen consumption may have utility as criteria for the assessment
      of human islet quality.

PMID- 16278580
TI  - The presence of HLA-directed antibodies after heart transplantation is associated
      with poor allograft outcome.
AB  - BACKGROUND: The clinical significance of HLA-directed antibodies newly detected
      after transplantation (HT) is controversial. METHODS: Seventy-one HT recipients
      consented to enroll. Mean follow-up time was 28 months (range 6-48). Panel
      reactive antibody (PRA) analysis was performed on posttransplant sera (2 weeks,
      1, 2, 3, 6, and 12 months and annually thereafter) using Flow-PRA. A mean of
      6.9+/-1.2 serum samples per patient were obtained. Severity of cellular rejection
      was measured using the ISHLT grading system. Coronary angiography and
      intravascular ultrasound (IVUS) studies were performed annually to evaluate
      severity of allograft vasculopathy. RESULTS: Twenty-five recipients had newly
      detected HLA-directed antibodies during the first year postHT. HLA class I
      antibodies were detected in 18 patients (25.4%), and class II in 11 patients
      (15.5%). The majority of donor recipient pairs were HLA mismatched (4.6+/-1.2 of
      the six major HLA antigens). Only mismatches at HLA-A locus had significant
      association with de novo posttransplant antibody formation. Length of ischemia
      time was correlated with early and sustained presence of de novo HLA-directed
      antibodies postheart transplant. Importantly, an association between de novo HLA
      directed antibodies and cellular rejection was notes (P=0.0002). De novo HLA
      class II directed antibodies are also associated with IVUS documented
      vasculopathy (P<0.002). Finally, death due to allograft failure is associated
      with the presence of de novo formed HLA class II directed antibodies (P=0.008).
      CONCLUSIONS: Identifying the formation of de novo HLA-directed antibodies
      following heart transplantation may predict allograft outcome. This, in turn, may
      serve as a tool for individualization of immunosuppression protocols in heart
      transplant recipients.

PMID- 16278581
TI  - Analysis of the complex effect of donor's age on survival of subjects who
      underwent heart transplantation.
AB  - BACKGROUND: Only half of the patients waiting for a heart transplant undergo
      surgery, whereas several patients continue to die while on the waiting list.
      Donor organ availability still represents a major problem with respect to
      reducing the length of the cardiac transplant waiting list. One option to improve
      donor availability is the use of so called "marginal donors." The aims of the
      present study are to analyze the short-mid term survival of cardiac transplanted
      patients in Italy, and investigate the effect of donor age on prognosis. METHODS:
      A prospective cohort study including all adult patients who underwent heart
      transplantations in Italy was used to analyze the main factors contributing to
      organ survival. RESULTS: From 1995-2002, 2,504 adult subjects underwent a cardiac
      transplant, and were followed up for a period of 540.9 days. Overall, 1-year
      graft survival was 83.1%. Organs from donors older than 55 years had a lower
      survival than organs from younger donors. By multivariate analysis, both donor's
      and recipient's age seem to be important determinants of graft survival. A more
      sophisticated analysis shows that the trend of the risk of graft failure
      according to donor's age is not linear, with a peak at age 47.3 years, and
      differs according to sex. CONCLUSIONS: Results from the present analysis suggest
      that the association between heart transplant survival and donor's age is not a
      linear one, but follows a complex mathematical model, with influences of sex, at
      least in our sample.

PMID- 16278582
TI  - Antifungal management practices and evolution of infection in organ transplant
      recipients with cryptococcus neoformans infection.
AB  - BACKGROUND: Therapeutic practices for Cryptococcus neoformans infection in
      transplant recipients vary, particularly with regards to antifungal agent
      employed, and duration of therapy. The risk of relapse and time to recurrence is
      not known. We assessed antifungal treatment practices for cryptococcosis in a
      cohort of prospectively followed organ transplant recipients. METHODS: The
      patients comprised 83 transplant recipients with cryptococcosis followed for a
      median of 2.1 and up to 5.2 years. RESULTS: Patients with central nervous system
      infection (69% vs. 16%, P = 0.00001), disseminated infection (82.7% vs. 20%, P =
      0.00001), and fungemia (29% vs. 8%, P = 0.046) were more likely to receive
      regimens containing amphotericin B than fluconazole as primary therapy. The use
      of fluconazole, on the other hand, was more likely for infection limited to the
      lungs (64% vs. 14%, P = 0.00002). Survival at 6 months tended to be lower in
      patients whose CSF cultures at 2 weeks were positive compared to those whose CSF
      cultures were negative (50% vs. 91%, P = 0.06). Maintenance therapy was employed
      in 68% (54/79) of the patients who survived >3 weeks. The median duration of
      maintenance therapy was 183 days; 55% received maintenance for > or = 6 months
      and 25% for >1 year. Relapse was documented in 1.3% (1/79) of the patients.
      CONCLUSIONS: A majority of the organ transplant recipients with cryptococcosis
      receive maintenance antifungal therapy for 6 months with low risk of relapse.
      These data can assist in trials to assess the optimal therapeutic approach and
      duration of therapy for cryptococcosis in transplant recipients.

PMID- 16278583
TI  - Increased intracellular pro- and anti-inflammatory cytokines in bronchoalveolar
      lavage T cells of stable lung transplant patients.
AB  - BACKGROUND: Allograft rejection remains a major cause of morbidity and mortality
      following lung transplantation and is associated with an increased expression of
      T-cell proinflammatory cytokines. We have recently shown that peripheral blood T
      cell proinflammatory cytokine production was significantly reduced in stable lung
      transplant patients consistent with immunosuppression therapy. However, analysis
      of inflammatory cytokine profiles in bronchoalveolar lavage (BAL) T cells may be
      more relevant than peripheral blood T cells for assessing graft status. METHODS:
      To investigate the immunomodulatory effects of currently used immunosuppressive
      regimens on BAL T-cell cytokine production, whole blood and BAL from stable lung
      transplant patients and control volunteers was stimulated in vitro and cytokine
      production by CD8+ and CD4+ T-cell subsets determined using multiparameter flow
      cytometry. RESULTS: There was a significant decrease in T-cell proinflammatory
      cytokine production in BAL compared with blood from control subjects but not
      transplant patients. Anti-inflammatory cytokine IL-4 was increased in BAL
      compared with blood from both groups. There was a significant increase in
      IFNgamma, IL-2, IL-4, TGFbeta, and TNFalpha production by CD8 T cells and
      IFNgamma and TNFalpha production by CD4 T cells in BAL from transplant patients
      compared with controls. CONCLUSIONS: We have shown decreased T-cell pro- and anti
      inflammatory cytokine production in BAL compared with blood in control subjects
      but not in stable lung transplant patients. Current immunosuppression protocols
      have limited effect on T-cell proinflammatory cytokine production in BAL but do
      upregulate anti-inflammatory cytokines IL-4 and TGFbeta. Drugs that effectively
      reduce T-cell proinflammatory cytokine production in BAL may improve current
      protocols for reducing graft rejection in these patients.

PMID- 16278584
TI  - Effects of immunosuppressive agents on magnesium metabolism early after
      allogeneic hematopoietic stem cell transplantation.
AB  - BACKGROUND: The calcineurin inhibitors, cyclosporine A (CSA) and tacrolimus,
      cause hypomagnesemia by suppressing reabsorption of magnesium (Mg) from renal
      tubules. To assess whether the effect on Mg metabolism after allogeneic
      hematopoietic stem cell transplantation (HSCT) differs among calcineurin
      inhibitors, we prospectively evaluated the Mg metabolism in recipients of
      allogeneic HSCT who received CSA or tacrolimus METHODS: Patients who underwent
      allogeneic HSCT were enrolled. CSA and tacrolimus were given by continuous
      infusion starting from day -1. Serum Mg and the total amount of urinary Mg
      excretion were measured once before starting of CSA or tacrolimus, and once
      weekly after HSCT for 4 weeks. Mg was supplemented with magnesium l-aspartate by
      continuous infusion to maintain the serum Mg level >1.4 mEq/L. RESULTS: Thirty
      six patients were evaluated (12 in the CSA group, 24 in the tacrolimus group).
      The serum Mg level began to decrease in both groups at the first week after HSCT,
      and the mean serum Mg levels were significantly lower in the tacrolimus group
      than in the CSA group from the first to the third week. The total amount of
      urinary Mg excretion and Mg supplementation began to increase in both groups at
      the second week after HSCT, and the amounts in the tacrolimus group were
      significantly higher than those in the CSA group. CONCLUSIONS: Although both
      calcineurin inhibitors increased urinary Mg excretion and caused hypomagnesemia
      shortly after HSCT, the effect was more significant with tacrolimus than with
      CSA. This observation may explain the higher incidence of renal impairment and
      encephalopathy in patients receiving tacrolimus.

PMID- 16278585
TI  - Results from a human renal allograft tolerance trial evaluating T-cell depletion
      with alemtuzumab combined with deoxyspergualin.
AB  - BACKGROUND: Perioperative lymphocyte depletion induces allograft tolerance in
      some animal models, but in humans has only been shown to reduce immunosuppressive
      requirements. Without maintenance immunosuppression, depleted human renal
      allograft recipients experience rejection characterized by infiltration of the
      allograft with monocytes and macrophages. T-cell depletion combined with a brief
      course of deoxyspergualin (DSG), a drug with inhibitory effects on monocytes and
      macrophages, induces tolerance in nonhuman primates. We therefore performed a
      trial to determine if lymphocyte depletion with alemtuzumab combined with DSG
      would induce tolerance in humans. METHODS: Five recipients of live donor kidneys
      were treated perioperatively with alemtuzumab and DSG and followed
      postoperatively without maintenance immunosuppression. Patients were evaluated
      clinically, by flow cytometry, and by protocol biopsies analyzed
      immunohistochemically and with real-time polymerase chain reaction. Results were
      compared to previously studied patients receiving alemtuzumab alone or standard
      immunosuppression. RESULTS: Despite profound T-cell depletion and therapeutic DSG
      dosing, all alemtuzumab/DSG patients developed reversible rejection that was
      similar in timing, histology, and transcriptional profile to that seen in
      patients treated with alemtuzumab alone. Chemokine expression was marked prior to
      and during rejections. CONCLUSIONS: We conclude that treatment with alemtuzumab
      and DSG does not induce tolerance in humans. Chemokine production may not be
      adequately suppressed using this approach.

PMID- 16278586
TI  - Hand-assisted retroperitoneoscopic live donor nephrectomy: experience from the
      first 75 consecutive cases.
AB  - BACKGROUND: The two major life-threatening complications associated with
      laparoscopic live donor nephrectomy are sudden severe bleeding and intestinal
      injury. A combined technique-hand-assisted and retroperitoneoscopic (HARS)
      reduces the risk of these life-threatening complications. In this study, we
      report on our experience from the first 75 consecutive HARS operations. METHODS:
      The data has been collected prospectively according to intention to treat and
      includes all consecutive donors operated with the HARS technique. Warm ischemia
      time, operating time, and blood loss were recorded. Complications, convalescence,
      and allograft outcome were followed postoperatively with a mean follow-up of 701
      (range 60-1438) days. RESULTS: The mean operating time was 138 (range 85-260)
      minutes and the mean warm ischemia time 175 (85-510) seconds. The operative time
      was significantly longer in male donors. The mean bleeding was 176 (50-700) ml.
      There were no conversions to open surgery. Major complications comprised one
      pulmonary embolus and one donor required 2 units of blood transfusion. One donor
      was reoperated due to suspicion of trocar hernia. Nine patients experienced minor
      complications (fever, n=4; urinary tract infection, n=2; chylous ascites, n=1;
      orchialgia, n=1; subcostal pain, n=1). All except two kidneys had immediate onset
      of function. Neither of these could, however, be attributed to the donor
      operation. One recipient experienced urinary leakage and one a stenosis.
      Recipient and graft survival were 99% and 96%, respectively. CONCLUSIONS: We
      conclude that HARS facilitates the procedure by enabling short operating times
      and at the same time significantly reducing the risks associated with endoscopic
      live donor nephrectomy.

PMID- 16278587
TI  - Laparoscopic donor nephrectomy gene expression profiling reveals upregulation of
      stress and ischemia associated genes compared to control kidneys.
AB  - We compared gene expression profiles from six donor kidneys prior to surgical
      manipulation to six kidneys removed after laparoscopic donor nephrectomy (LDN)
      and several hours of CO2 pneumoperitoneum. Biopsies were obtained from renal
      cortex and hybridized to Affymetrix HG-U133A GeneChips. For control kidneys, we
      identified 1380 genes present on all six samples that had a signal intensity
      >1,000. Functional classification of these revealed genes for cellular signaling
      (201; 15%), regulation of transcription (156; 11%), cellular transport (144; 10%)
      and cellular metabolism (111; 8%). A class comparison between the controls and
      LDN kidneys yielded 865 differentially expressed genes. Functional classification
      of the 502 genes differentially upregulated in LDN kidneys identified
      associations with apoptosis, cell adhesion, cell signaling, regulation of cell
      growth/proliferation, immune/inflammation, ischemia/stress response and
      proteolysis/peptidolysis. These data demonstrate an altered renal transcriptome
      induced by several hours of CO2 pneumoperitoneum and laparoscopic surgery
      characterized by upregulation of ischemia and injury associated genes.

PMID- 16278588
TI  - Marked Differences in acute cellular rejection rates between living-donor and
      deceased-donor liver transplant recipients.
AB  - BACKGROUND: : Due to ongoing organ donor shortage, an increasing number of adult
      live-donor liver transplants (LDLT) are being performed. The aims of this study
      were to compare the incidence of ACR between recipients of live- and deceased
      donor liver transplants, and to note any differences in ACR among related and
      unrelated living-donor recipients. METHODS: : Sixty-four adults undergoing LDLT
      between 1998-2001 were closely matched with a deceased recipient. Statistical
      comparisons in ACR between the live- and deceased-donor groups were based on the
      differences between the ACR rates of each LDLT patient and the corresponding
      matched deceased recipient. Analyses were performed separately for pairs in which
      the living donor was not related to the recipient, was a nonsibling relative, or
      was a sibling. RESULTS: : Live- and deceased-donor recipients underwent a similar
      number of liver biopsies. In all, 16/50 (32%) of the biopsied LDLT patients had
      ACR compared to 36/49 (73%) of the deceased-donor recipients. ACR rates of living
      donors and their deceased-donor matches did not differ significantly for the
      unrelated living donors, but did differ for the nonsibling related (P=0.03) and
      the sibling LDLT (P=0.03). The results were similar when comparing rates of high
      degree ACR for unrelated, nonsibling related, and sibling pairs. High-degree ACR
      differences in the sibling LDLT group were significantly greater than in the
      nonsibling group (P=0.05). CONCLUSIONS: : Rates of ACR and high-degree ACR are
      decreased in living-related liver transplant recipients. This difference is
      likely genetically related as ACR rates are lower in recipient-donor pairs of
      increasing genetic similarity.

PMID- 16278589
TI  - Sedative drug requirements during bronchoscopy are higher in cystic fibrosis
      after lung transplantation.
AB  - BACKGROUND: We noted that patients with cystic fibrosis tended to need higher
      doses of sedatives during bronchoscopy. We undertook this study to assess the
      sedative drug doses administered during bronchoscopy in lung transplant
      recipients and to assess if there is a change in the dosage requirements over
      time following lung transplantation. METHODS: In all, 773 transbronchial biopsy
      procedures performed via flexible bronchoscopy were analyzed in 140 consecutive
      lung transplant recipients. Conscious sedation was achieved with intermittent
      boluses of intravenous midazolam and fentanyl. Intravenous propofol boluses of 10
      to 30 mg were administered when optimal sedation was not achieved with midazolam
      doses of 0.20 to 0.25 mg/kg and fentanyl 2 to 2.5 micrograms/kg. RESULTS: Mean
      doses of midazolam and fentanyl administered were 0.15+/-0.07 mg/kg (range 0.02
      to 0.44 mg/kg) and 1.8+/-0.8 micrograms/kg (range 0.1 to 6.67 micrograms/kg)
      respectively. Midazolam and fentanyl doses administered to patients with cystic
      fibrosis were the highest compared to those with other disease types (P<0.0001).
      Examining the sedative doses administered over time following transplantation,
      there was a significant linear (P<0.001) and quadratic (P=0.0023) effect of time
      for midazolam and a significant linear (P=0.003) and a trend (P=0.08) for a
      quadratic effect for fentanyl. Propofol was effectively used in seven lung
      transplant recipients in whom adequate sedation could not be achieved with high
      doses of midazolam and fentanyl. CONCLUSIONS: There is an increase in sedative
      drug requirement with time for both midazolam and fentanyl after transplantation,
      which is significantly higher in patients with cystic fibrosis.

PMID- 16278590
TI  - Efficacy and safety of adefovir dipivoxil in kidney recipients, hemodialysis
      patients, and patients with renal insufficiency.
AB  - BACKGROUND: This study analyzes the biochemical, serological, and virological
      efficacy and the safety of adefovir dipivoxil in patients with renal
      disturbances. METHODS: Twelve patients with lamivudine-resistant hepatitis B
      virus (HBV) chronic infection were treated for a median time of 15 (3-19) months.
      The daily dosage was 10 mg initially and then adjusted according to renal
      function. RESULTS: Median (range) ALT values remained stable: 55 (13-117) and 37
      (17-266) UI/L. After the 12th month, the median decline in serum HBV DNA was from
      8.76 (6.3-9.7) to 2.97 (1.15-5.65) log10 Eq/ml (median decline of -5.5 log10). No
      virologic breakthrough was observed. One of the six HBeAg-positive patients lost
      HBe Ag but without HBe seroconversion; none had HBs Ag loss. There were no
      significant clinical and biochemical adverse effects. In the 11 nonhemodialysed
      patients, the creatinine clearance significantly improved from 70 (30-100) to 88
      (38-125) ml/mn (P=0.01) and the mean serum creatinine levels increased only
      slightly from 114 (91-839) to 130 (81-561) micromol/ml (NS). Serum phosphorus
      remained stable. The urinary level of protein decreased from 0.16 (0.08-8.63) to
      0.12 (0.01-0.74) g/day (NS). CONCLUSIONS: Adefovir dipivoxil is safe for the
      treatment of chronic hepatitis B in patients with varying degrees of renal
      dysfunction and lamivudine-resistant HBV and results in biochemical and
      virological efficacy similar to that reported in the general population.

PMID- 16278591
TI  - Prevention of renal impairment by continuous infusion of human atrial natriuretic
      peptide after liver transplantation.
AB  - BACKGROUND: Acute renal failure occurring immediately after liver transplantation
      and requiring hemodialysis is a major problem resulting in a poor prognosis. We
      investigated the efficacy of human atrial natriuretic peptide, which has potent
      natriuretic effects and unique protective effects for glomeruli in preventing
      acute renal failure after liver transplantation. METHODS: Thirty-seven patients
      who underwent live donor liver transplantation with model for end-stage liver
      disease scores greater than 15 were the subjects of the study. Subjects were
      prospectively randomized into two groups: patients that received synthetic human
      atrial natriuretic peptide infusion (Group H: n=19) and those that received
      conventional diuretics, furosemide and potassium canrenoate (Group C: n=18). The
      peri- and postoperative changes in hemodynamic status and renal function were
      compared between the two groups. RESULTS: There were no statistical differences
      in the changes in hemodynamic status between groups. Hemodialysis was required
      after liver transplantation in nine patients, two in Group H and seven in Group C
      (P=0.04). Postoperative creatinine clearance was higher in Group H (P=0.03).
      Aldosterone level was suppressed in group H (P=0.006). CONCLUSIONS: Continuous
      infusion of synthetic human atrial natriuretic peptide might be effective for
      preventing acute renal failure requiring hemodialysis after liver
      transplantation.

PMID- 16278593
TI  - Inhibition of human dendritic cell maturation and function by the novel
      immunosuppressant FK778.
AB  - BACKGROUND: FK778, a derivative of the active leflunomide-metabolite, A77 1726,
      has been shown to be a powerful immunosuppressant in several transplantation
      models, particularly efficient in the prevention of chronic allograft rejection.
      However, the cellular and molecular mechanisms underlying these effects of FK778
      have not been investigated yet in detail. Because dendritic cells (DCs) are the
      most potent antigen-presenting cells (APCs) and are essential for the initiation
      of immune responses including acute and chronic allograft rejection, we
      investigated whether FK778 affects this particular cell type. METHODS: Allogeneic
      T cell stimulation by FK778-treated human monocyte-derived DCs was determined by
      mixed leukocyte cultures. Surface molecule expression was analyzed by flow
      cytometric analysis and cytokine production by ELISA from culture supernatants.
      Activation of NF-kappaB in DCs was assessed by electrophoretic mobility shift
      assays. RESULTS: Treatment of DCs with FK778 inhibited their potency to stimulate
      allogeneic T cells. In line, LPS- and CD40L-induced upregulation of DC surface
      activation markers and production of IL-12 was significantly inhibited,
      irrespective of whether cells were treated during or after the monocyte to DC
      differentiation period. The effects of FK778 on DCs were not reversible by
      exogenous uridine indicating that FK778 acts independently of its action as an
      inhibitor of pyrimidine synthesis. On the signaling level, activation of NF
      kappaB, the essential transcription factor involved in DC maturation and
      function, was markedly inhibited by FK778. CONCLUSIONS: Inhibition of activation
      and function of DCs as the central APCs may significantly contribute to the
      immunosuppressive profile of FK778 when applied after allogeneic organ
      transplantation.

PMID- 16278592
TI  - Trefoil factor expression in biliary epithelium of graft-versus-host disease of
      the liver after allogeneic hematopoietic cell transplantation.
AB  - BACKGROUND: The aims of this study were to determine the presence of trefoil
      factor family-3 (TFF3) expression in biliary epithelial cells (BECs) of chronic
      graft-versus-host disease (cGVHD) of the liver after allogeneic hematopoietic
      cell transplantation, to compare such expression in chronic liver diseases (CLD)
      with/without predominantly biliary disease, and to assess the effect of bile duct
      injury on the degree of TFF3 expression in BECs of cGVHD. METHODS: A total of 82
      paraffin-embedded liver biopsy samples were reviewed. These samples were
      basically divided into two distinct groups according to the presence of ductal
      injury: group 1 with CLD and predominantly biliary disease (n=26: 17 cGVHD and 9
      primary biliary cirrhosis [PBC]) and group 2 with CLD and predominantly
      parenchymal liver disease (n=56: 20 steatohepatitis and 36 chronic viral
      hepatitis). Group 2 was used as the controls. Immunohistochemistry was performed
      using a polyclonal anti-TFF3 antibody. Real-time quantitative PCR was used for
      the detection of TFF3 mRNA expression. RESULTS: Positive TFF3 immunohistochemical
      staining and the presence of TFF3 messenger RNA gene expression was demonstrably
      higher in group 1 than that in group 2 (P<0.0001 and P<0.05, respectively). No
      significant difference in terms of positive TFF3 stained BECs between GVHD and
      PBC samples was observed (P>0.05). The extent of TFF3 expression in GVHD samples
      with severe ductal injury were significantly more common than that of GVHD
      samples with mild/moderate ductal injury (P<0.0001). CONCLUSIONS: The expression
      of TFF3 in cGVHD of the liver is increased in response to bile duct damage and
      repair. Such expression seems to be related the severity of ductal injury.

PMID- 16278594
TI  - Inhibition of Src kinases combined with CD40 ligand blockade prolongs murine
      cardiac allograft survival.
AB  - BACKGROUND: Members of the Src family of tyrosine kinases (SFKs) are requisite
      signaling molecules activated by multiple receptors during immune responses.
      Their expression and catalytic activity has not been characterized in allograft
      rejection in vivo. METHODS: We measured expression and catalytic activity of SFKs
      in MHC- mismatched murine cardiac allografts. We also examined the effects of a
      Src inhibitor (CGP77675) with or without anti-CD154 mAb on graft survival,
      histology, and expression and catalytic activity of SFKs within the grafts.
      RESULTS: In acutely rejecting allografts from untreated controls, total activity
      of Hck and Lyn increased 10-fold, predominantly reflecting increases in the
      amount of protein. Total activity of Lck increased only fourfold, reflecting
      small changes in both the amount of protein and specific activity. One dose of
      anti-CD154 plus CGP77675 markedly diminished cellular infiltration, but survival
      was only moderately prolonged despite inhibition of all SFKs in the rejected
      grafts. Two doses of anti-CD154 plus CGP77675 allowed permanent graft acceptance
      in 60% of recipients even after discontinuation of the inhibitor. Both rejected
      and long surviving grafts showed increased activity of all SFKs. Recipients that
      rejected their grafts showed serum alloantibody production, and grafts rejected
      during treatment demonstrated deposition of complement indicating the
      contribution of antibody to rejection. CONCLUSIONS: The myeloid and B cell Src
      family kinases, Hck and Lyn, rather than the T cell Src kinase Lck, show the
      greatest increase in expression and total activity in rejecting allografts. Both
      rejected and long-surviving grafts show significant increases in SFK expression
      and acitivity.

PMID- 16278595
TI  - Analysis of KIR ligand incompatibility in human renal transplantation.
AB  - Natural killer cells express killer immunoglobulin-like receptors (KIR) that bind
      to MHC class I antigens. Lack of self-MHC on the target cell can cause NK-cell
      mediated killing. Here, we analyzed the effect of KIR ligand incompatiblity on
      renal allograft survival in humans. Kidney recipient/donor pairs were separated
      according to their HLA-Cw alleles and HLA-Bw4 specificity which are considered
      epitopes for KIR. A total of 2,757 renal transplants were examined. Graft
      survival rates were computed according to the Kaplan-Meier method. No effect of
      KIR ligand matching on graft survival was observed in cadaver kidney transplants.
      Our results indicate that KIR ligand matching cannot be recommended as a strategy
      for improving renal allograft survival.

PMID- 16278597
TI  - Acute graft pyelonephritis: a potential cause of acute rejection in renal
      transplant.
AB  - Acute graft pyelonephritis is a common complication in renal transplant
      recipients. The consequences of this complication on kidney allograft survival
      remain controversial. Bacterial infection is likely to activate the immune
      system, potentially leading to acute or chronic rejection. Here, we report for
      the first time two documented cases of acute rejection occurring shortly after
      acute graft pyelonephritis, suggesting that pyelonephritis can initiate acute
      rejection. The immunologic process leading to the alloimmune response is
      discussed. These reports suggest that acute rejection should be questioned in
      case of atypical graft outcome in the context of acute graft pyelonephritis.

PMID- 16278596
TI  - Simultaneous vs. sequential laparoscopic bilateral native nephrectomy and renal
      transplantation.
AB  - We reviewed our experience with simultaneous single incision bilateral native
      nephrectomy and renal transplantation in 11 patients (Group 1), compared to seven
      recipients who underwent staged laparoscopic bilateral nephrectomy followed by
      kidney transplantation (Group 2). Mean age, donor source, sex, cause of ESRD, and
      specimen size were similar in both groups (P=0.1). All Group 2 patients and 9 of
      11 Group 1 patients had autosomal-dominant polycystic kidney disease.
      Perioperative Group 1 complications included: bowel injury, transplant urine
      leak, necrotic pancreatitis, delayed bowel movement, and severe shoulder pain
      secondary to diaphragmatic irritation. Seven (63.6%) Group 1 patients required an
      additional surgical procedure: midline incisional hernia, repair ureteral
      fistula, and repair enterocutaneous fistula. One Group 1 patient lost his graft
      secondary to bowel injury and intra-abdominal sepsis. No major complications,
      reoperations, or graft loss occurred in Group 2. For simultaneous bilateral
      native nephrectomy and kidney transplantation, over 60% of patients required an
      additional surgical procedure. Laparoscopic bilateral nephrectomy followed by
      kidney transplantation is a safe and feasible alternative.

PMID- 16278598
TI  - Allograft loss in renal transplant recipients with cryptococcus neoformans
      associated immune reconstitution syndrome.
AB  - This study describes the association of allograft loss and immune reconstitution
      syndrome (IRS) in the course of Cryptococcosis neoformans infection in renal
      transplant recipients. Patients comprised 54 renal allograft recipients with
      cryptococcosis in a prospective, multicenter study. IRS developed in 5.5% (3/54)
      of the renal transplant recipient with C. neoformans infection. The renal
      allograft was lost to chronic rejection in 66% (2/3) of the patients with
      cryptococcosis who developed IRS compared to 5.9% (3/51) of those who did not
      (P=0.012). Kaplan-Meier survival analysis showed that subsequent to cryptococcal
      infection the probability of allograft survival was significantly lower in
      patients who developed IRS compared to those who did not develop IRS (P=0.0004).
      Temporal association of graft loss with IRS suggests a common pathophysiologic
      basis for these entities with implications relevant for the optimal management of
      renal transplant recipients with cryptococcosis.

PMID- 16278599
TI  - HLA matching and posttransplant lymphoproliferative disease after lung
      transplantation.

PMID- 16278601
TI  - Bone mineral density after liver transplantation.

PMID- 16278602
TI  - Retransplantation for acute liver failure due to combined antiviral agents in an
      HIV-HCV coinfected liver transplant recipient.

PMID- 16278604
TI  - Breast cancer risk: is postmenopausal hormone therapy ever safe?

PMID- 16278605
TI  - Quantifying estrogen treatment effect on vagina tissue: cellular age matters.

PMID- 16278606
TI  - Anomalies in health care attributable to the separation of medicine and
      dentistry.

PMID- 16278607
TI  - Coronary artery calcification and osteoporosis: is estrogen an important link?

PMID- 16278608
TI  - The new hormone therapy problem: do we solve it with long-cycle progesterone
      therapy?

PMID- 16278609
TI  - Postmenopausal hormone therapy and breast cancer: a systematic review  and meta
      analysis.
AB  - OBJECTIVE: There is a rapidly evolving debate on the indications and appropriate
      duration of therapy for postmenopausal hormone therapy. The objective of this
      meta-analysis was to examine the specific relationships of postmenopausal
      estrogen therapy (ET), postmenopausal combined (estrogen-progestogen) hormone
      therapy (CHT), and the incidence of breast cancer. DESIGN: We performed
      computerized searches of MEDLINE and CancerLit through September 2003 and
      reviewed reference lists of retrieved studies and meta-analyses. We included
      English-language studies that identified noncontraceptive postmenopausal hormone
      use; reported on the risks of "current use" of ET and/or CHT and breast cancer
      incidence; were case-control, cohort, or experimental; and reported either an
      odds ratio (OR), relative risk (RR), or HR with CIs. Two investigators were
      involved during all stages of study selection and independently extracted all
      data selected for inclusion in meta-analyses. RESULTS: Meta-analysis of 13
      studies of ET and breast cancer (700,000 women) resulted in an OR of 1.16 (95%
      confidence limits [CL] 1.06, 1.28), with estimates for less than 5 years use 1.16
      (1.02, 1.32) and more than 5 years use 1.20 (1.06, 1.37). Meta-analysis of eight
      studies of CHT and breast cancer (650,000 women) resulted in an OR of 1.39 (95%
      CL 1.12, 1.72), with estimates for less than 5 years use 1.35 (1.16, 1.57) and
      more than 5 years use 1.63 (1.22, 2.18). CONCLUSIONS: Data from observational
      studies support the association of increased but considerably different risks for
      breast cancer incidence among current users of ET and CHT. These represent the
      first pooled estimates for ET. CHT estimates correspond to those from randomized
      trials.

PMID- 16278610
TI  - Effects of estrogen on proton secretion via the apical membrane in vaginal
      ectocervical epithelial cells of postmenopausal women.
AB  - OBJECTIVE: To understand estrogen regulation of proton (H(+)) secretion by human
      vaginal-ectocervical epithelial cells and the mechanisms involved. DESIGN:
      Primary-tertiary cultures of human normal vaginal-ectocervical epithelial cells
      were generated from surgical specimens of premenopausal women (aged 37-46 years)
      and of postmenopausal women (aged 53-65 years). Cells were grown on filters, and
      measurements were made of changes in extracellular pH (pHo) in the contraluminal
      (CL) and luminal (L) solutions 30 minutes after shifting cells to basic salt
      solution. RESULTS: Upon shifting cells to basic salt solution, CL-pHo decreased
      from 7.4 to 7.25, and was not affected by removal of intracellular estrogens or
      treatment with estradiol. L-pHo decreased from 7.4 to 7.05 in cells of
      premenopausal women, and from 7.4 to 7.20 in cells of postmenopausal women.
      Removal of intracellular estrogens attenuated the decrease in L-pHo in cells of
      premenopausal women (only to 7.20). In cells of premenopausal women stripped of
      estrogens, treatment with 10 nM 17beta-estradiol restored the decrease in L-pHo.
      In estrogen-stripped cells of postmenopausal women, treatment with estradiol
      augmented luminal acidification but to a lesser degree than in cells of
      premenopausal women (L-pHo of 7.15 vs 7.05). In cells of pre- and postmenopausal
      women, the addition in the L solution of bafilomycin-A(1), a specific inhibitor
      of the vacuolar-H(+)-ATPase (V-H(+)-ATPase), blocked the decrease in L-pHo.
      CONCLUSIONS: Human vaginal-ectocervical epithelial cells acidify constitutively
      their luminal solution, and the effect is mediated by active H(+) secretion by V
      H(+)-ATPase expressed predominantly in the apical cell membrane. Estrogen
      deprivation attenuates, and treatment with 17beta-estradiol augments, active H(+)
      secretion. Finally, cells of postmenopausal women actively secrete H(+) via
      apically located V-H(+)-ATPase, but the effect is lesser, and estrogen failed to
      augment active H(+) secretion, as in cells of premenopausal women. These data
      suggest that in addition to hypoestrogenism, other factors of the aging process
      affect the capacity of vaginal-ectocervical cells to secrete acid.

PMID- 16278611
TI  - Periodontal assessment of postmenopausal women receiving risedronate.
AB  - OBJECTIVE: The purpose of this study was to compare periodontal status of
      postmenopausal women with mild to moderate osteoporosis who use risedronate
      therapy with those who do not. DESIGN: In this cross-sectional study, a total of
      60 age-matched postmenopausal women with mild to moderate osteoporosis diagnosed
      by a bone density scan T score below -2.5 at either spine or hip were divided
      into two groups. Women in the experimental group had used systemic risedronate
      once weekly (35 mg) for at least 3 months. Women in the control group had never
      used bisphosphonate therapy. The periodontal status of each subject was evaluated
      through a clinical periodontal examination including evaluation of periodontal
      probing depth, gingival recession, gingival index, plaque score, attachment loss,
      and alveolar bone level. The significance in differences between the two groups
      was assessed using two-tailed paired t tests. RESULTS: Significant differences (P
      < 0.05) were found between risedronate and control groups for periodontal probing
      depth (2.6 vs 2.9 mm), gingival index (0.37 vs 0.71), plaque score (56.2 vs
      77.0), attachment loss (2.8 vs 3.2 mm), and alveolar bone level (3.1 and 4.0),
      respectively. Gingival recession parameters did not differ significantly. Five of
      six periodontal parameters evaluated show that postmenopausal women with mild to
      moderate osteoporosis using risedronate therapy have healthier periodontal status
      than those who do not use bisphosphonates. CONCLUSIONS: Women using risedronate
      therapy show significantly less plaque accumulation, less gingival inflammation,
      lower probing depths, less periodontal attachment loss, and greater alveolar bone
      levels. These observations suggest that risedronate therapy may play a beneficial
      role in periodontal status.

PMID- 16278612
TI  - Differences in association of bone mineral density with coronary artery
      calcification in men and women: the Rancho Bernardo Study.
AB  - OBJECTIVE: Whether osteoporosis and calcification of atherosclerotic plaque are
      two independent, age-related processes or linked by similar mechanisms of bone
      mineralization and plaque calcification is unknown. This study examines the sex
      specific association between bone mineral density (BMD) and coronary artery
      calcification with a particular focus on hormone therapy (HT). DESIGN:
      Participants were 180 men (aged 47-86 years) and 186 women (aged 58-81 years)
      without a history of heart disease who had hip and spine BMD assessed by dual
      energy x-ray absorptiometry and coronary artery calcium score (CACS) measured by
      electron-beam computed tomography. Calcium scores were categorized into
      none/minimal (<or=10), mild (11-100), moderate (101-399), and severe (>or=400).
      Ordinal and binary logistic regressions examined the associations between site
      specific BMD and CACS. RESULTS: In men and women not using HT, there was no age
      independent association between BMD at any site and CACS. In contrast, among
      current HT users an inverse association of BMD with coronary artery calcification
      was observed at the total hip (odds ratio [OR] = 0.56, 95% CI, 0.33-0.95),
      trochanter (OR = 0.55, 95% CI, 0.32-0.93), and intertrochanter area (OR = 0.60,
      95% CI, 0.41-0.86) after adjustment for age and other risk factors. Other
      skeletal sites showed similar, but not statistically significant, associations (P
      < 0.1). CONCLUSION: Lack of association between BMD and CACS in men and women not
      using HT and the inverse association in women on HT suggest that the association
      between coronary and bone calcium might be mediated by estrogen.

PMID- 16278613
TI  - Endometrial safety and bleeding pattern during a five-year treatment with long
      cycle hormone therapy.
AB  - OBJECTIVE: To determine compliance, the incidence of untoward effects, and
      endometrial safety in postmenopausal women treated with 3-month sequential
      hormone therapy for up to 5 years. DESIGN: A prospective, uncontrolled
      multicenter study of 129 women treated with 0.625 mg conjugated estrogens daily
      plus 10 mg medroxyprogesterone acetate for 14 days every third month. Endometrial
      biopsy samples were taken before the initiation of the study and then yearly
      during the next 5 years. Bleeding patterns were recorded. RESULTS: Upon
      completion of the first 12 months of treatment, 76 of 126 biopsied women (60%)
      had secretory endometrium. After 5 years, this finding was reversed in biopsy
      specimens completed by 59 women, among whom 32 (56%) had insufficient or atrophic
      endometrium. We did not find any hyperplasia when the biopsy specimen was taken
      according to the protocol. One endometrial cancer was found by biopsy after 12
      months, but the subsequent hysterectomy showed no sign of cancer. Ultrasound
      determinations of mean endometrial thickness during therapy showed a thin
      endometrium (mean = 4 mm, range = 1-13 mm). Amenorrhea was reported by 6.2% of
      129 women after 12 months of treatment. Among the 59 women who completed the
      study, 71.2% had regular bleeding patterns every third month, 25.4% reported
      amenorrhea, and 3.4% had irregular bleeding patterns. CONCLUSIONS: The addition
      of 10 mg of medroxyprogesterone acetate for 14 days every third month to
      treatment with 0.625 mg of conjugated estrogens daily was well tolerated, and was
      associated with high endometrial safety.

PMID- 16278614
TI  - Comparative controlled trial of a novel oral estrogen therapy, estradiol acetate,
      for relief of menopause symptoms.
AB  - OBJECTIVE: To compare the efficacy and tolerability of a new oral estradiol
      prodrug, estradiol acetate, with micronized estradiol or conjugated equine
      estrogens for alleviation of postmenopausal vasomotor and urogenital symptoms.
      DESIGN: A total of 249 postmenopausal women experiencing seven or more moderate
      or severe vasomotor symptoms daily for 1 week or 60 or more symptoms in 1 week
      were randomized to 0.9 mg of estradiol acetate (n = 79), 1 mg of micronized
      estradiol (n = 85), or 0.625 mg of conjugated equine estrogens therapy (n = 85).
      Efficacy endpoints were the change in frequency and severity of vasomotor
      symptoms from baseline to week 12, participant-assessed urogenital symptoms, and
      investigator-assessed signs of vaginal atrophy. Efficacy results were considered
      equivalent if estradiol acetate was at least 80% as effective as estradiol and
      conjugated estrogens. RESULTS: At week 12, frequency of vasomotor symptoms
      decreased comparably in all groups, and at weeks 4 and 12, the decrease in
      frequency of symptoms was statistically equivalent for estradiol acetate and
      conjugated estrogens. Severity of vasomotor symptoms also improved comparably for
      all groups, with least squares mean decreases of 1.05 for estradiol acetate, 1.34
      for estradiol, and 1.17 for conjugated estrogens at week 12. Urogenital symptoms
      and vaginal signs showed similar improvement in all groups. Overall, the majority
      of adverse events were mild or moderate and consistent with estrogen therapy.
      CONCLUSION: Estradiol acetate 0.9 mg was comparable to 1 mg of estradiol and
      0.625 mg of conjugated equine estrogens in reducing the number and severity of
      vasomotor and urogenital symptoms in postmenopausal women. Oral estradiol acetate
      was well tolerated.

PMID- 16278616
TI  - Postmenopausal oral estrogen therapy and blood pressure in normotensive and
      hypertensive subjects: the Estrogen in the Prevention of Atherosclerosis Trial.
AB  - OBJECTIVE: To determine if 17beta-estradiol increases blood pressure in
      postmenopausal women. DESIGN: A total of 222 healthy postmenopausal women were
      randomly assigned to either 1 mg micronized 17beta-estradiol daily or placebo for
      2 years. Blood pressure measurements were obtained every other month and common
      carotid artery intima-media thickness measured every 6 months. Statistical
      analyses comparing longitudinal changes in systolic and diastolic blood pressure
      between treatment groups used a mixed general linear model including interaction
      terms to evaluate variations by age or estradiol level. RESULTS: Both placebo and
      estradiol groups showed small declines in systolic and diastolic blood pressure
      during the trial among the normotensive subjects and subjects on antihypertensive
      medications. However, the decline did not differ significantly between the
      groups. Treatment effects on systolic blood pressure differed significantly by
      the age of the subject (interaction P value = 0.04) with younger women on
      estradiol showing on average a rise in systolic blood pressure, and older women a
      decline. The association between serum estradiol level and systolic blood
      pressure showed a similar modification with age (P = 0.03). Changes in systolic
      blood pressure in women on estradiol were positively correlated with intima-media
      thickness progression (P = 0.03). CONCLUSIONS: Overall, 17beta-estradiol did not
      influence changes in blood pressure in normotensive or hypertensive women. The
      effect of 17beta-estradiol treatment on systolic blood pressure may be influenced
      by a woman's age. Estradiol may increase systolic blood pressure in younger
      postmenopausal women, while having the opposite effect in older postmenopausal
      women.

PMID- 16278615
TI  - Long-term safety of drospirenone-estradiol for hormone therapy: a randomized,
      double-blind, multicenter trial.
AB  - OBJECTIVE: The purpose of this multicenter, double-blind, randomized, parallel
      group study was to determine the effect of thirteen 28-day cycles of drospirenone
      combined with estradiol, compared with estradiol alone, on the endometrium of
      postmenopausal women. DESIGN: Postmenopausal women not on hormone therapy but
      with an intact uterus were enrolled (N = 1,147); 1,142 were evaluated.
      Participants were randomly assigned to treatment with 1.0 mg of estradiol alone
      (E(2) monotherapy) or 1.0 mg of estradiol plus 0.5, 1.0, 2.0, or 3.0 mg of
      drospirenone (DRSP/E(2)). Endometrial biopsies were performed at baseline, at 7
      months if indicated, and at study end in the 13th month. Safety was evaluated
      with peripheral blood samples for hematology, liver and renal function, and
      lipids, along with vital signs and interval medical evaluations. RESULTS: When
      compared with estradiol alone, combinations of drospirenone and estradiol were
      effective in protecting against endometrial hyperplasia. The probability of
      hyperplasia was 0.060 (95% CI, 0.043-0.078) for the E(2) monotherapy group, 0.007
      for the 2-mg DRSP/E(2) group, and nonsignificant for the remaining
      drospirenone/estradiol groups. Endometrial bleeding decreased in all treatment
      groups over time. The combination of drospirenone and E(2) relieved menopausal
      symptoms and resulted in improvements in health-related quality-of-life measures.
      There were no significant adverse events, and effects on triglycerides, total
      cholesterol, and high-density lipoprotein cholesterol were positive. CONCLUSIONS:
      The use of drospirenone combined with estradiol provides protection against
      endometrial hyperplasia, reduces endometrial bleeding with time, and relieves
      menopausal symptoms. There were no safety issues and blood pressure was reduced
      in women with hypertension.

PMID- 16278617
TI  - Use of dong quai (Angelica sinensis) to treat peri- or postmenopausal symptoms in
      women with breast cancer: is it appropriate?
AB  - OBJECTIVE: Regarding the growing use of alternative therapies for peri- or
      postmenopausal symptoms, we evaluated the effect of a water extract of Angelica
      sinensis (dong quai), used for peri- or postmenopausal relief, on the
      proliferation of estrogen receptor-positive (MCF-7) and negative (BT-20) breast
      cancer cells in vitro. DESIGN: The present study was designed to investigate the
      growth-modulating effect of dong quai water extract, alone or in the presence of
      17beta-estradiol and 4-hydroxytamoxifen, on MCF-7 and BT-20 cell cultures using
      MTT proliferation assay. RESULTS: The water extract of dong quai dose-dependently
      and significantly stimulated the proliferation of MCF-7 cells with a weak
      estrogen-agonistic activity in the presence of 17beta-estradiol, as evidenced by
      the significant suppression by 4-hydroxytamoxifen. Meanwhile, the extract
      significantly exerted a growth-stimulating effect on BT-20 in a dose-dependent
      manner with or without 17beta-estradiol. No obvious difference was found in the
      growth of BT-20 cells treated with the extract in the presence of 17beta
      estradiol or 4-hydroxytamoxifen. CONCLUSIONS: The water extract of dong quai
      stimulated the growth of MCF-7 cells, possibly dependent of weak estrogen
      agonistic activity, and augmented the BT-20 cell proliferation independent of
      estrogen receptor-mediated pathway. The present study provides data regarding the
      estrogen-like activity of dong quai, which might assist in decision making on
      herbal therapy use by women at risk for both estrogen-sensitive and insensitive
      breast cancer. Because of the lack of clinical data demonstrating the potential
      side effects of dong quai, its use in herbal preparations for the treatment of
      peri- or postmenopausal symptoms, especially in women with breast cancer,
      warrants caution pending further study.

PMID- 16278618
TI  - Oral hormone therapy with 17beta-estradiol and 17beta-estradiol in combination
      with norethindrone acetate in the prevention of bone loss in early postmenopausal
      women: dose-dependent effects.
AB  - OBJECTIVE: A 2-year multicenter, double-blind, randomized, placebo-controlled
      study examined the efficacy and safety of different doses of 17beta-estradiol
      (E(2)) alone and continuous-combined oral formulations of E(2) and norethindrone
      acetate (NETA) versus placebo in the prevention of bone loss in newly menopausal
      women. DESIGN: Patients were randomized to one of seven groups: placebo, E(2)
      0.25 mg, E2 0.5 mg, E(2) 1 mg, E(2) 1 mg/NETA 0.25 mg, E(2) 1 mg/NETA 0.5 mg, or
      E(2) 2 mg/NETA 1 mg. Treatment was a once-daily tablet taken for 26 months. The
      primary efficacy endpoint was the change in bone mineral density (BMD) at the
      lumbar spine, measured by dual-energy x-ray absorptiometry, at screening and at
      13, 19, and 26 months. BMD changes at the femoral neck and trochanter were also
      assessed. Biochemical markers of bone metabolism were measured at baseline, and
      at 3, 6, 13, 19, and 26 months. Histological diagnoses of endometrial samples
      were tabulated for each treatment group. RESULTS: A total of 327 women were
      randomized and 189 women completed the 2-year trial. BMD at the lumbar spine
      decreased 2.3% in the placebo group. The lowest dose of unopposed E(2) prevented
      bone loss at the spine and hip. Significant increases in spine BMD compared with
      placebo occurred in all groups of treatment with E(2) and were more pronounced in
      the combination groups. Compared with placebo, women receiving active treatment
      experienced greater reductions in bone resorption markers. The effects were
      evident by 6 months and generally remained stable thereafter. Adverse events,
      primarily associated with the endometrium, were the most common reasons for
      discontinuation. CONCLUSIONS: There is a dose-dependent effect of E(2) on BMD.
      The addition of NETA seems to enhance the response in BMD observed with E(2). Low
      doses of E(2) (1 mg and lower) can be considered for the prevention of
      osteoporosis, while titrating the hormone dose to individual patient's needs.

PMID- 16278620
TI  - Dried plum reverses bone loss in an osteopenic rat model of osteoporosis.
AB  - OBJECTIVE: We previously reported the efficacy of dried plum (Prunus domestica
      L.) in preventing ovariectomy-induced bone loss in a rat model of osteoporosis
      and improving bone biomarkers in postmenopausal women. The present study
      evaluated whether dried plum was able to restore bone mass in osteopenic
      ovariectomized rats. DESIGN: Ninety-day-old Sprague-Dawley rats were either sham
      operated (Sham; one group) or ovariectomized (Ovx; five groups) and were fed a
      standard diet for 40 days to establish bone loss and subsequently experimental
      treatments were initiated. Sham, Ovx control, and Ovx + 17beta-estradiol (E2; 10
      microg/kg body weight per day) animals continued to receive the standard diet,
      whereas the remaining three Ovx groups received the following dietary treatments:
      Ovx + 5% dried plum (low dose), Ovx + 15% dried plum (medium dose), and Ovx + 25%
      dried plum (high dose). After 60 days, blood and bone specimens were collected
      for analyses. RESULTS: Dried plum, as low as 5%, was effective in restoring
      femoral and tibial bone density. Dried plum increased lumbar bone density as
      well, with HD achieving a statistical significance. The increase in femoral bone
      density of dried plum-fed rats resulted in improved bone quality as indicated by
      6.9% and 6.0% improvement in overall yield and ultimate force, respectively.
      Varying doses of dried plum were also able to significantly improve trabecular
      microarchitectural properties in comparison with ovariectomized controls.
      CONCLUSIONS: The improvement in biomechanical properties of long bones due to
      dried plum, in part, may be due to the favorable microstructural changes as
      evident by enhanced tibial bone volume and connectivity. Loss of bone volume
      accompanied by loss of trabecular connectivity is generally believed to be an
      irreversible process, but our observations suggest that dried plum improves
      trabecular microstructure of tibia after losses have already occurred.

PMID- 16278619
TI  - Mutational screening of the coding region of growth differentiation factor 9 gene
      in Indian women with ovarian failure.
AB  - OBJECTIVE: To establish the risk associated with mutations in the coding region
      of GDF9 gene in Indian women with ovarian failure. DESIGN: This case-control
      study was designed for mutational analysis of the GDF9 coding region in a cohort
      of women with premature ovarian failure (n = 127), primary amenorrhea (n = 58),
      and secondary amenorrhea (n = 10) compared with controls (n = 220). RESULTS: This
      case-control study revealed eight mutations in the GDF9 gene, including five
      novel mutations: c.1-8C>T, c.199A>C (p.Lys67Glu), c. 205C>T, c.646G>A
      (p.Val216Mat), and c.1353C>T, and three documented mutations: c.398-39C>G,
      c.447C>T, and c.546G>A. Missense mutation c.199A>C was present in 4 of 127
      premature ovarian failure (POF) cases and 1 of 10 secondary amenorrhea cases. The
      c.646G>A mutation was present in two POF cases. Both missense mutations were
      absent in controls. Genotype distribution of c.447C>T was significantly different
      in POF cases than controls (chi(2) = 5.93, P = 0.05). We chose two frequent
      single-nucleotide polymorphisms (c.398-39C>G, c.447C>T) for haplotyping and found
      that the C-T haplotype was significantly higher in patients (P = 0.03), whereas
      the C-C haplotype was representative of the control group. CONCLUSIONS: We report
      two rare missense mutations, c.199A>C and c.646G>A, which are associated with
      ovarian failure. The presence of the c.447>T mutation might indicate a higher
      risk for POF. Haplotype C-T was significantly associated with ovarian failure,
      whereas the C-C haplotype was representative of the control group.

PMID- 16278621
TI  - The effect of education and counseling services on compliance to therapy of women
      taking hormone therapy for the first time.
AB  - OBJECTIVE: The purpose of this experimental research was to examine the effect of
      hormone therapy (HT)-related education and counseling on compliance. DESIGN: The
      119 women in both the experimental and the control group were being seen in a
      referral maternity and women's health teaching hospital's menopause outpatient
      clinic. Similarity between experimental and control groups was ensured using one
      to-one pairing. The data were collected using a questionnaire and a follow-up
      form. The experimental group was given group education and an educational booklet
      on the first day they began therapy and counseling in the third and sixth months
      of therapy. The control group was not given counseling or education. Chi-square
      was used in data evaluation. RESULTS: There was no difference between the groups
      at the third month for those who were continuing HT (P > 0.05), but at the sixth
      month a significant difference was found (P < 0.05). The primary reason for
      stopping HT at the third month in the experimental group was fear of cancer and
      in the control group it was the side effects of HT. At 6 months, the primary
      reason for stopping HT in the experimental group was, again, fear of cancer but
      in the control group it was the woman's desire not to continue. There was no
      significant difference in the groups at either 3 or 6 months in experiencing
      benefits or side effects from HT (P > 0.05). CONCLUSION: Education and counseling
      services given by nurses or other health care personnel have an effect on long
      term compliance with HT.

PMID- 16278622
TI  - A review of bioidentical hormones.

PMID- 16278626
TI  - Recommendations for airway control and difficult airway management.

PMID- 16278627
TI  - Informed consent to proposed course of medical treatment: recent case law
      stances.
AB  - Developments in ethics, deontology and case law, along with the related
      increasing demand for patient autonomy in decision-making in health care, led the
      President of SIAARTI in 2000 to request the Bioethics Commission to revise the
      documentation on informed content the Study Group on Anesthesia Safety had
      issued. In response to the request, a multidisciplinary study group was called to
      examine the ethical, psychological, clinical, legal and medicolegal issues
      related to informed consent and to draw up a document that would provide for the
      implementation of the procedure for information and consent proposed in the model
      of disclosed information and consent for anesthesia approved by the SIAARTI
      Advisory Board. The model is to be viewed as evidence for an established
      anesthetist-patient relationship and as a useful record in case of legal or
      insurance liability litigation. In Italy, failure to obtain consent to medical
      treatment has assumed growing legal implications. Since 1992, the failure to
      obtain consent has become part of case law, an exemplary instance of which is the
      case of a surgeon that was closed in 2002 with the judgment of the Corte di
      Cassazione (Italian Supreme Court), section I, of 29/05/2002. The judgment found
      that, in the absence of express implementation of the Oviedo Convention, a
      physician is always legitimated to performed therapeutic treatment deemed
      necessary for preserving the life of a patient in his or her care, even in the
      absence of explicit consent, with the sole but significant exception of
      unequivocal refusal of treatment.

PMID- 16278628
TI  - Sepsis and organ dysfunction: an ongoing challenge.
AB  - In recent years the problem of infection has become increasingly significant,
      especially in intensive care hospital wards such as Intensive Care Units (ICU),
      emergency medicine, surgery and critically ill patient care departments. Sepsis
      is a complex, multifactorial syndrome that can develop into conditions of
      different severity, described as severe sepsis or septic shock. In these
      conditions the triggering event may coincide with the functional impairment of
      one or more vital organs or systems, thus leading to poorer prognosis in patients
      with overt signs of sepsis or systemic inflammation syndromes. The available data
      are quite alarming, as most prevention and treatment is performed empirically and
      requires considerable human and technological resources. Clinical signs are often
      misleading and, in some circumstances, it may be difficult or even impossible to
      identify the source of the infection which might otherwise be removed relatively
      simply, using proper antimicrobial treatment or a less invasive surgical removal
      of the area from which the infection originates based on needle-guided radiology.
      In addition, the complex pathophysiological mechanisms involved can be an
      obstacle to gaining a full understanding of the various biohumoral interactions
      or mediators action mechanisms. It may not be easy to enroll patients belonging
      to homogeneous groups in terms of age, underlining disease, immune profile or
      genetic predisposition, although the use of specific severity indexes has proved
      helpful also to establish the prognosis. Although the interpretation of
      generalised inflammation as a warning sign also in the absence of clear signs of
      infection or a state of overt inflammation has to rely largely on simple
      intuition, it has helped to drive experimental and clinical research work towards
      the investigation of interaction between different factors such as infection and
      sepsis, or inflammation and coagulation. An additional useful tool is the
      possibility of modulating the endothelial response which may support the process
      of disseminated thrombosis typical of sepsis evolution. In this context the
      improvement of standards of care can shed light on the efficacy of different
      treatments.

PMID- 16278629
TI  - Comparison of sequential combined spinal-epidural anesthesia and spinal
      anesthesia for cesarean section.
AB  - AIM: The aim of our study was to prove that by using sequential combined spinal
      epidural (CSE) anesthesia it is possible to overcome the limits connected to the
      use of spinal anesthesia (SA) alone for elective cesarean section. METHODS: We
      examined 100 women submitted to cesarean section; SA was administered to 50
      patients and sequential CSE technique to the other 50. In every woman before
      execution of the anesthesia we infused 500 mL of a plasma expander and a previous
      administration of 5 mg of ephedrine. The CSE was executed at the L1-L2
      intervertebral space, administering in spinal anesthesia 5 mg of levobupivacaine
      with 5 _g of sufentanil, and in peridural anesthesia 10-12 mL of levobupivacaine
      0.25% according to the patient's height. The peridural catheter for postoperative
      analgesia was then positioned. In the group of women submitted only to SA, 7.5-8
      mg of levobupivacaine was injected, according to the patient's height, in the L1
      L2 intervertebral space, with 5 _g of sufentanil. We considered the following
      adverse effects: hypotension; bradycardia; vomiting; intraoperative discomfort
      and motor block. RESULTS: The results obtained showed that, with a P < or = 0.05,
      the incidence of motor block (P < 0.001), discomfort (P < 0.001) and hypotension
      (P = 0.021) in the SA group is greater than in the CSE group. The difference in
      the incidence of vomiting (P = 0.147) and bradycardia (P = 0.067) between the 2
      groups is not statistically significant. CONCLUSIONS: In our opinion sequential
      CSE can be considered an important step forward in the regional anesthesia used
      for elective cesarean section.

PMID- 16278630
TI  - Metabolic stress during hypoglycaemia clamp assessed by microdialysis.
AB  - AIM: Microdialysis allows the biochemical analysis of interstitial fluids as a
      bedside procedure. This technique is of interest to evaluate the glucose
      dependent metabolism in hypoglycaemic patients. It was the aim to perform
      subcutaneous and blood microdialysis during hypoglycaemic clamp experiments in 12
      healthy young men to reveal basis data for critical care microdialysis practice.
      METHODS: The hyperinsulinaemic clamp was induced with a continuous infusion of
      1.5 mU min(-1) kg(-1) insulin (H-insulin, Hoechst, Frankfurt, Germany). A 20%
      dextrose solution simultaneously was infused at a variable rate to control blood
      glucose levels. For hypoglycaemia blood glucose levels were reduced to 40 mg/dL
      for a 30 min period. Glucose, lactate, pyruvate and glycerol concentrations were
      semicontinuously measured. RESULTS: The absolute concentrations of glucose and
      glycerol in blood vs subcutaneous microdialysate were significant different
      during observation. Until the end of hypoglycaemia, glucose concentration in both
      compartments declined in parallel, followed by an increase thereafter. During the
      clamp the subcutaneous glycerol increased threefold, whereas blood glycerol rose
      with a delay of 15 min and increased only twofold. After the clamp in both
      compartments glycerol values normalized. The lactate-pyruvate-ratio persisted in
      normal range throughout the examination. CONCLUSIONS: In our experiment
      subcutaneous lipolysis increased faster and more profound than blood
      microdialysis. We propose the microdialysis technique as an additional monitoring
      tool in hypoglycaemia patients.

PMID- 16278631
TI  - Correlation between hyperglycemia and mortality in a medical and surgical
      intensive care unit.
AB  - AIM: The aim of this study was to assess the correlation between hyperglycemia
      and mortality in a group of patients admitted to a medical and surgical ICU and
      to evaluate if the association between hyperglycemia and reason of ICU admission
      significantly worsens patients' outcomes. METHODS: A retrospective clinical study
      was conducted in the ICU of a University Hospital. Four-hundred and twelve adult
      patients admitted to our ICU were enrolled. The blood glucose level was measured
      at the time of admission and daily at 2-4 h intervals. When the glucose level
      exceeded 180 mg/dL, an insulin bolus or a continuous infusion were performed to
      maintain the glucose level at or below 180-200 mg/dL. RESULTS: Analysing the mean
      blood glucose levels of patients with the receiver operating characteristic (ROC)
      curve, it resulted that the blood glucose level of 141.7 mg/dL had higher
      sensitivity (76%) and specificity (56.5%) to discriminate the probability of
      death. In other words, in patients in whom the mean blood glucose levels were
      greater than 141.7 mg/dL, the probability of death was higher (26.62%) than in
      the group of patients in whom a strict blood glucose control was maintained
      (13.55%) (P = 0.0017). CONCLUSIONS: A strict blood glucose control seems to be
      crucial, even in a medical and surgical ICU. The need for intensive insulin
      therapy, even by means of continuous infusion of insulin, to obtain the
      normalization of blood glucose levels, appears essential.

PMID- 16278632
TI  - Mechanisms of cell protection by adaptation to chronic and acute hypoxia:
      molecular biology and clinical practice.
AB  - Several experimental and clinical studies have shown that specific biochemical
      and molecular pathways are involved in the myocardial and skeletal muscle cell
      tolerance to acute and/or chronic hypoxic injury. A number of different factors
      were proposed to play a role in the preservation of tissue viability, but to a
      few of them a pivotal role in the adaptive mechanisms to hypoxic stimuli could be
      ascribed. Starting from the observation that mitochondrial electron transport
      chain (ETC) enzymic complexes are the targets of oxygen reduced availability,
      most of data are compatible with a mechanism of enzymic adaptation in which the
      nitric oxide (NO) generation plays the major role. If the partial and reversible
      NO-induced inhibition of ETC enzymic complexes represents the most rapid and
      prominent adaptive mechanism in counteracting the damaging effects of hypoxia,
      the sarcolemmal and mitochondrial K+(ATP) channels activation results to be
      closely involved in cytoprotection. This process is depending on protein kinase C
      (PKC) isoform activation triggered by reactive oxygen species (ROS) generation,
      adenosine triphosphate (ATP) depletion and Ca++ overload. It is well known that
      all these factors are present in hypoxia-induced oxidative damage and
      mitochondrial Ca++ altered pools represent powerful stimuli in the damaging
      processes. The activation of mitochondrial K+(ATP) channels leads to a
      significant reduction of Ca++ influx and attenuation of mitochondrial Ca++
      overload. Closely linked to these adaptive changes signal transduction pathways
      are involved in the nuclear DNA damage and repair mechanisms. On this context, an
      essential role is played by the hypoxia-induced factor-1alpha (HIF-1alpha) in
      terms of key transcription factor involved in oxygen-dependent gene regulation.
      The knowledge of the biochemical and molecular sequences involved in these
      adaptive processes call for a re-evaluation of the therapeutic approach to
      hypoxia-induced pathologies. On this light, some specific aspects of the
      therapeutic management of critically ill patients are taken into consideration
      and discussed in relation to the cellular biodynamics.

PMID- 16278633
TI  - Factors associated with mortality and long time survival in patients undergoing
      modified Bentall operations.
AB  - AIM: We report our results on mortality, morbidity and long time events after
      composite graft replacement of the aortic root and ascending aorta/aortic arch
      and factors associated with them. METHODS: Seventy-four patients, aged 52 years
      (15-73) underwent modified ''button'' Bentall operation. The indication for
      operation was acute dissection in 29 (39%) patients, chronic dissection in 3
      (4%), aortic regurgitation after previous replacement of the ascending aorta
      because of aortic dissection in 2 (3%) and non dissecting aneurysm in 40 (54%).
      Concommitant procedures were (partial) replacement of the aortic arch in 11 (15%)
      and coronary artery bypass grafting in 5 (7%). Six patients (8%) had undergone
      previous cardiac surgery. Mean follow up was for 49 +/- 46 months (maximum 198).
      RESULTS: Length of intensive care unit (ICU) stay was 3 days (1-72). Hospital
      mortality was 12%. Factors significantly associated with hospital mortality were:
      aortic dissection, cardiopulmonary bypass time, aortic cross clamp time, deep
      hypothermic circulatory arrest, low cardiac output syndrome, revision due to
      bleeding, renal failure requiring hemofiltration, multisystemic organ failure and
      sepsis. None of these factors was significantly associated with long term
      survival. Survival rates including hospital deaths were 86%, 84%, 75% and 75%
      after 1, 3, 5 and 7 years respectively. Pseudoaneurysm at the composite graft
      occurred in 3%, infection of the prosthesis in 1%. Neither valve thrombosis nor
      thromboembolic events occurred postoperatively. CONCLUSIONS: Modified Bentall
      operation is a demanding operation with acceptable hospital mortality. The long
      time survival rates are good and the big majority of patients is eventfree after
      operation.

PMID- 16278635
TI  - Early postoperative candida colonization in alimentary canal in patients
      undergoing open heart surgery.
AB  - AIM: To examine the frequency and factors predisposing to candidiasis in the
      digestive tract in the early postoperative period after open heart surgery.
      METHODS: One hundred patients undergoing open heart surgery were enrolled in this
      study. Patients were divided into 2 groups in regard to Candida spp.
      colonization. Group A means increased Candida spp. colonization after open heart
      surgery (31/100). Group B indicates unchanged Candida spp. colonization after
      open heart surgery (69/100). Samples were obtained from both oral and anal mucosa
      in 3 different periods of operation: 1) preoperatively (stage 1), 2) at the end
      of the first hour in the intensive care unit (stage 2), 3) 24 hours after
      operation (stage 3). Findings were compared with both preoperative and
      intraoperative parameters. For fungal isolation Sabourauds dextrose agar and
      blood agar were used. RESULTS: In Group A (31), there was a significant
      relationship between the samples in stage 1 and 2 (p=0.031), and also a
      significance between stage 1 and 3 (p=0.048). Comparison between Candida positive
      and negative groups (Group A and B) did not reflect any statistical significance
      (p>0.05). CONCLUSIONS: Candida colonization in the alimentary canal in the early
      postoperative period after open heart surgery is due to individual preoperative
      features. However, early postoperative Candida colonization in the digestive
      tract is not a risk factor for sepsis unless the patient has an additional risk
      factor leading to prolongation of length of stay in the intensive care unit.

PMID- 16278634
TI  - Diltiazem prophylaxis reduces incidence of atrial fibrillation after coronary
      artery bypass grafting.
AB  - AIM: To evaluate the prophylactic effect of diltiazem on the incidence of atrial
      arrhythmia (fibrillation and/or flutter) following coronary artery bypass
      grafting (CABG). Data were retrospectively gathered. METHODS: Patients undergoing
      elective CABG by one surgeon at one institution over a three-year period were
      considered for inclusion. Those selected were divided into 3 groups: A (patients
      placed on intravenous diltiazem intraoperatively, then converted to oral
      diltiazem upon initiation of oral intake); B (patients started on oral diltiazem
      upon initiation of oral intake without prior intravenous diltiazem); and C
      (patients receiving no diltiazem). A comparison of postoperative rates of atrial
      fibrillation was made between the 3 (demographically balanced) groups using
      logistic regression. RESULTS: Two hundred and eighty seven patients met inclusion
      criteria. The incidence of postoperative atrial fibrillation in the entire sample
      was 19.9% (57/287). Incidence of postoperative atrial fibrillation within each
      group was: A = 16.3% (22/135); B = 12.7% (7/55); C = 28.9% (28/97). Statistical
      significance was demonstrated for the following comparisons: A versus C (p =
      0.0451) and B versus C (p = 0.0065). In an alternate model groups A and B were
      combined and compared to C (p = 0.0181). CONCLUSIONS: A lower incidence of atrial
      fibrillation following CABG was observed in patients treated prophylactically
      with diltiazem. Differences were statistically significant whether the drug was
      administered intravenously and orally (A) or only orally (B). Diltiazem, which
      has an established role in the management of atrial fibrillation, may prove to be
      well suited for prophylaxis due to low cost and relative safety.

PMID- 16278636
TI  - A new cryoablation device for surgical therapy of atrial fibrillation.
AB  - During the last years, atrial fibrillation was treated more and more by surgical
      ablation. Due to serious complications with the available devices, new tools were
      developed. We report on the first successful cryoablation procedure with a new
      device in a patient with a high-grade mitral valve insufficiency (III-IV) and
      paroxysmal atrial fibrillation.

PMID- 16278637
TI  - Penetration to the aortic wall by a metallic airway stent. A successfully treated
      case with left pneumonectomy and aortic repair.
AB  - Metallic airway stents were used widely at the beginning of airway stent use, but
      an accumulation of cases has revealed complications due to their use. A patient
      who received a Gianturco Z stent for bronchial tuberculosis suffered massive
      haemoptysis due to stent migration into the aortic wall. Left pneumonectomy with
      aortic repair was successfully performed. We suggest that metallic stents should
      not be used for benign airway palliation, as they may later cause life
      threatening complications.

PMID- 16278638
TI  - Is carotid endarterectomy in octogenarians more dangerous than in younger
      patients?
AB  - AIM: The risk for developing stroke increases with the advancing age, peaking
      over age 80. In elderly patients, carotid endarterectomy may provide prophylaxis
      against stroke. Aim of our study was to compare patients 80 years or older with
      patients younger than 80 undergoing carotid endarterectomy. Endpoints were
      perioperative mortality and morbidity. METHODS: From January 1996 to December
      2002, 1 659 patients underwent a 1 733 carotid endarterectomy for a symptomatic
      or asymptomatic significant carotid lesion. Among them, 125 patients were 80
      years or older. We analyzed death and stroke rate from cerebrovascular accidents,
      TIA as well as non cerebrovascular complications and death rate postoperatively
      and in the long term follow-up. The Pearson's chi-squared(2) test was used for
      the statistical analysis on risk factors, morbidity and mortality. The Log rank
      test was used for cumulative stroke-free and survival rates between the 2 groups
      (level of confidence p<0.05). RESULTS: Risk factors were similar in both groups.
      No statistical difference was observed in the stroke, TIA, mortality and stroke
      free rates between the 2 groups. CONCLUSIONS: The results of our study show that
      perioperative and postoperative mortality and morbidity as well as the long-term
      stroke-free rate does not differ significantly in patients 80 years or older
      compared to patients younger than 80 undergoing carotid endarterectomy.

PMID- 16278639
TI  - Experimental development of an endovascular graft for thoraco-abdominal aortic
      aneurysm repair.
AB  - AIM: Current treatment of thoraco-abdominal aortic aneurysms is surgical. Despite
      significant advances in surgical technique and anesthetic management, significant
      morbidity and mortality remain associated with their repair. In compliance with
      principles of reducing postoperative morbidity, we developed a thoraco-abdominal
      endovascular graft in experimental models of type III and type IV thoraco
      abdominal aortic aneurysm. This device had to preserve the vascularization of the
      visceral arteries while ensuring full aneurysmal exclusion. METHODS: Six
      implantations of the endovascular graft were performed. This graft was a modular
      system, made of: 1) a custom made main body containing 4 prosthetic visceral
      branches, 2) 4 self-expandable stent-grafts connecting prosthetic visceral
      branches with visceral arteries, 3) a custom made tubular endovascular graft
      connecting the main body with one of the iliac arteries. RESULTS: On angiographic
      controls, full aneurysmal exclusion was achieved while maintaining visceral
      artery perfusion. At the end of each procedure, the experimental model was
      opened. Macroscopic examination showed harmonious thoraco-abdominal endovascular
      graft deployments, without abnormal component constraint or kinking. There was no
      discordance between macroscopic and angiographic RESULTS:  CONCLUSIONS: Our
      experimental work led to the development of a thoraco-abdominal endovascular
      graft, demonstrating feasibility of thoraco-abdominal aneurysm endoluminal
      treatment on an in vitro model close to the anatomical conditions observed in
      human pathology.

PMID- 16278640
TI  - Reoperations on the ascending aorta and aortic root. Early and late results?
AB  - AIM: We have retrospectively evaluated our results after aortic root and
      ascending aorta reoperations to determine risk factors of early death and late
      mortality. METHODS: From January 1986 to April 2002, 73 patients underwent
      ''reoperative'' procedures on the aortic root and the ascending aorta. The mean
      age was 56.1+/-13.4 years and males numbered 62 (84.9%). The most frequent
      indication for reoperation was degenerative aortic aneurysm (49.3%) followed by
      post-dissection aneurysm (11%). Aortic root replacement with composite valve
      graft was performed in 47 patients (64.4%) and with aortic homograft in 2 (2.7%).
      Nineteen patients (26%) underwent ascending aorta replacement with tubular graft,
      and 4 (5.5%) underwent tailoring aortoplasty of the ascending aorta. RESULTS: The
      30-day mortality rate was 16.4% (12 patients). Mortality following elective
      operations was 8%, and that following urgent or emergency operations was 34.8%
      (p=0.002). Late survival of hospital survivors at 1, 5 and 10 years was 93.8%,
      77.7% and 37%, respectively. In the multivariate Cox regression analysis chronic
      renal failure (p=0.003) and urgent or emergency operation (p=0.018) were found to
      be independent predictors of late mortality. CONCLUSIONS: Reoperations on the
      ascending aorta can be accomplished with acceptable early mortality and
      satisfactory long-term RESULTS: More radical treatment of the aortic pathology at
      the initial operation may reduce the need for further reoperations. A careful
      follow-up is extremely important for detecting complications of the first
      operation or progression of the aortic pathology before an emergency operation,
      predictive of poorer early and late outcome, is needed.

PMID- 16278641
TI  - Which distal anastomosis should be used in PTFE femoro-tibial bypass?
AB  - AIM: The PTFE prosthesis represents an alternative to the autologous saphenous
      vein in femoro-tibial revascularization for limb salvage in the absence of venous
      material in the patient. The aim of our study is to confirm the validity of PTFE
      revascularization and determine the best distal anastomosis in terms of patency
      using 3 different techniques. We carried out a retrospective analysis, evaluating
      patients who underwent PTFE femoro-tibial revascularization for critical
      ischemia. METHODS: Between January 1998 and June 2002 we performed 46 femoro
      tibial revascularizations at the Vascular Surgery Division of the Poliambulanza
      Hospital in Brescia using a PTFE prosthesis, from a total of 192 infrainguinal
      revascularizations (24%). All patients presented a critical ischemia, with
      trophic lesions or gangrene in 76% of the cases (35/46) and who were previously
      treated unsuccessfully with medical therapy. Seventeen cases (36%) were a redo
      bypass due to previously failed revascularization. In all cases the saphenous
      vein was not available due to past peripheral or coronary revascularization
      (45%), saphenectomy (20%) or inadequate diameter (35%). The distal anastomoses
      were performed on the peroneal artery in 29 cases, on the anterior tibial artery
      in 14 cases and on the posterior tibial artery in 3 cases. The distal anastomosis
      was performed by interposing a segment of vein between the prosthesis and the
      tibial artery in 12 cases; in 22 cases the interposition was performed using a
      vein patch, and in the remaining 12 cases a PTFE prosthesis provided with a
      premanufactured expanded anastomosis (Distaflo(c)) was used. RESULTS: Average
      follow-up was 22.5 months (range: 3-48 months). The primary and secondary patency
      rate at 48 months, calculated with the Life table method, was 35% and 47%,
      respectively. Limb salvage in the same time period was 56%. Depending on the
      anastomosis performed (Distaflo(c), vein patch, distal vein) we obtained a
      secondary patency rate of 31%, 62%, and 44% respectively after 48 months with a
      significant difference between distal vein patch and the other two anastomoses
      (p<0.001). CONCLUSIONS: The PTFE bypass on the tibial artery performed for limb
      salvage in the absence of a saphenous vein represents a valid alternative to
      other types of prostheses with a patency percentage that is acceptable in the
      medium term. Within our study population, anastomosis by vein patch interposition
      gave better results than other types of tibial anastomosis.

PMID- 16278642
TI  - Endovascular treatment of a post-traumatic thoracic false aneurysm in an
      adolescent. A case report.
AB  - A 17 year old healthy young man suffered a motor-vehicle accident with severe
      polytrauma. During the rehabilitation a slight hypertension and a blood pressure
      difference of 30-40 mmHg between arms and legs was recognized. Mindful of a
      possible aortic lesion, an angio-magnetic resonance imaging (MRI) showed a
      2.7x4.2 cm thoracic false aneurysm at the descending aorta. About 1 month after
      initial trauma, a Talent stent was implanted. The postinterventional period was
      uneventful. The patient was discharged on the 5th postoperative day.

PMID- 16278643
TI  - Harvest of the radial artery: technique of the skeletonization and pedicle
      preparation.
AB  - Nowadays, radial artery grafts play a significant role in coronary artery
      revascularization, however, harvesting techniques are not standardized. We
      developed various surgical techniques for radial artery harvesting considering
      the anatomic landmarks of the foramen, including conventional surgery (with
      scissors and clips) and procedures with ultrasonic scalpel and retrieving the
      radial artery graft in a pedicle or in a skeletonized manner.

PMID- 16278644
TI  - Late outcome and perioperative complications for surgery of locally recurrent
      bronchogenic carcinoma.
AB  - AIM: Many doubts involve a 2(nd) surgical approach for local relapse of non small
      cell lung cancer (NSCLC) since iterative resections represent a well-recognized
      treatment in second primary lung cancer (SPLC). METHODS: The medical reports of
      patients who underwent surgical resection, between 1988 and 2002, were reviewed.
      All patients submitted to 2(nd) operation were examined according to Martini and
      Melamed criteria to distinguish between local recurrence and second primary lung
      cancer. RESULTS: Complete resection for NSCLC was performed in 1 386 patients.
      Nineteen patients were submitted to surgery for local recurrence (17 men and 2
      women) and mean age at the time of 1(st) operation was 61 years (range 41-78
      years). The 1(st) operation consisted of lobectomy in 15 cases, anatomical
      segmentectomy in 2 and wedge resection in 2. The 2(nd) pulmonary resection was
      completion pneumonectomy in 16 cases, completion lobectomy in 2, wedge resection
      in 1. Major complications occurred in 26% and overall hospital mortality was 5%.
      Five-year survival after 2(nd) intervention was 31% and median survival 27
      months. Survival was better when the time between 1(st) resection and cancer
      relapse was longer than 14 months and when recurrence was intrapulmonary.
      CONCLUSIONS: A new malignant lesion can be operated if it is solitary and
      intrapulmonary, if accurate staging is negative and if the patient is able to go
      through 2(nd) surgery from cardiopulmonary evaluation.

PMID- 16278645
TI  - Subarachnoid-pleural fistula due to blunt chest trauma. A case report.
AB  - Subarachnoid pleural fistula (SPF) due to blunt chest trauma is rare. When SPF
      isn't associated with any neurological deficits, its clinical diagnosis is
      possible only with high degree of suspicion. Presentation symptoms include
      dyspnea and respiratory distress caused by the collection of cerebral-spinal
      fluid in the pleural cavity. Computed tomography scan after myelography is
      helpful in confirming the site of the fistula. Possible dangerous complications
      are infections or pneumoencephalus. Some cases resolved spontaneously after bed
      rest or pleural drainage alone, while others required surgical repair. We report
      a case of spontaneous closure after pleural drainage and a brief period of
      mechanical ventilation.

PMID- 16278646
TI  - Bilateral venous thrombosis and lymphedema in upper extremities of patient with
      lung cancer.

PMID- 16278647
TI  - Photoconversion of YFP into a CFP-like species during acceptor photobleaching
      FRET experiments.

PMID- 16278648
TI  - Ultrahigh-speed photochemical stimulation of neurons.

PMID- 16278649
TI  - Compensatory ingestion upon dietary restriction in Drosophila melanogaster.
AB  - Dietary restriction extends the lifespan of numerous, evolutionarily diverse
      species. In D. melanogaster, a prominent model for research on the interaction
      between nutrition and longevity, dietary restriction is typically based on medium
      dilution, with possible compensatory ingestion commonly being neglected. Possible
      problems with this approach are revealed by using a method for direct monitoring
      of D. melanogaster feeding behavior. This demonstrates that dietary restriction
      elicits robust compensatory changes in food consumption. As a result, the effect
      of medium dilution is overestimated and, in certain cases, even fully compensated
      for. Our results strongly indicate that feeding behavior and nutritional
      composition act concertedly to determine fly lifespan. Feeding behavior thus
      emerges as a central element in D. melanogaster aging.

PMID- 16278650
TI  - Glycomics: an integrated systems approach to structure-function relationships of
      glycans.
AB  - In comparison with genomics and proteomics, the advancement of glycomics has
      faced unique challenges in the pursuit of developing analytical and biochemical
      tools and biological readouts to investigate glycan structure-function
      relationships. Glycans are more diverse in terms of chemical structure and
      information density than are DNA and proteins. This diversity arises from
      glycans' complex nontemplate-based biosynthesis, which involves several enzymes
      and isoforms of these enzymes. Consequently, glycans are expressed as an
      'ensemble' of structures that mediate function. Moreover, unlike protein-protein
      interactions, which can be generally viewed as 'digital' in regulating function,
      glycan-protein interactions impinge on biological functions in a more 'analog'
      fashion that can in turn 'fine-tune' a biological response. This fine-tuning by
      glycans is achieved through the graded affinity, avidity and multivalency of
      their interactions. Given the importance of glycomics, this review focuses on
      areas of technologies and the importance of developing a bioinformatics platform
      to integrate the diverse datasets generated using the different technologies to
      allow a systems approach to glycan structure-function relationships.

PMID- 16278651
TI  - K+ waves in brain cortex visualized using a long-wavelength K+-sensing
      fluorescent indicator.
AB  - We synthesized a water-soluble, long-wavelength K(+) sensor, TAC-Red, consisting
      of triazacryptand coupled to 3,6-bis(dimethylamino)xanthylium, whose fluorescence
      increased 14-fold at 0-50 mM K(+) with K(+)-to-Na(+) selectivity >30. We
      visualized K(+) waves in TAC-Red-stained brain cortex in mice during spreading
      depression, with velocity 4.4 +/- 0.5 mm/min, and K(+) release and reuptake half
      times (t(1/2)) of 12 +/- 2 and 32 +/- 4 s, respectively. Aquaporin-4 (AQP4)
      deletion slowed K(+) reuptake about twofold, suggesting AQP4-dependent K(+)
      uptake by astroglia.

PMID- 16278652
TI  - G-tail telomere HPA: simple measurement of human single-stranded telomeric
      overhangs.
AB  - Accurate measurement of telomeric 3'-overhang (G-tail) lengths is essential for
      investigation of the biological effects of telomere dysfunction. G-tail telomere
      hybridization protection assay (Gt-telomere HPA) has the advantages of being
      simple to perform, accurate and highly sensitive for G tails as short as 20
      nucleotides. Furthermore, Gt-telomere HPA is specific and quantitative for human
      G tails, and can be used to assay cell lysates as well as genomic DNA.

PMID- 16278653
TI  - One-step analysis of protein complexes in microliters of cell lysate.
AB  - We present 'mix and measure' procedures for the analysis of protein complexes in
      microliters of crude human and mouse cell lysates using fluorescence correlation
      and crosscorrelation spectroscopy. We labeled interacting endogenous proteins by
      indirect immunofluorescence with all primary and secondary reagents added in one
      step. Especially for the screening of compounds interfering with interactions
      that depend on signaling-induced posttranslational modifications, the approach
      represents a major advance over existing protocols.

PMID- 16278654
TI  - Rapid neurotransmitter uncaging in spatially defined patterns.
AB  - Light-sensitive 'caged' molecules provide a means of rapidly and noninvasively
      manipulating biochemical signals with submicron spatial resolution. Here we
      describe a new optical system for rapid uncaging in arbitrary patterns to emulate
      complex neural activity. This system uses TeO(2) acousto-optical deflectors to
      steer an ultraviolet beam rapidly and can uncage at over 20,000 locations per
      second. The uncaging beam is projected into the focal plane of a two-photon
      microscope, allowing us to combine patterned uncaging with imaging and
      electrophysiology. By photolyzing caged neurotransmitter in brain slices we can
      generate precise, complex activity patterns for dendritic integration. The method
      can also be used to activate many presynaptic neurons at once. Patterned uncaging
      opens new vistas in the study of signal integration and plasticity in neuronal
      circuits and other biological systems.

PMID- 16278655
TI  - Versatile fluorescent derivatization of glycans for glycomic analysis.
AB  - The new field of functional glycomics encompasses information about both glycan
      structure and recognition by carbohydrate-binding proteins (CBPs) and is now
      being explored through glycan array technology. Glycan array construction,
      however, is limited by the complexity of efficiently generating derivatives of
      free, reducing glycans with primary amines for conjugation. Here we describe a
      straightforward method to derivatize glycans with 2,6-diaminopyridine (DAP) to
      generate fluorescently labeled glycans (glycan-DAP conjugates or GDAPs) that
      contain a primary amine for further conjugation. We converted a wide variety of
      glycans, including milk sugars, N-glycans, glycosaminoglycans and chitin-derived
      glycans, to GDAPs, as verified by HPLC and mass spectrometry. We covalently
      conjugated GDAPs to N-hydroxysuccinimide (NHS)-activated glass slides, maleimide
      activated protein, carboxylated microspheres and NHS-biotin to provide
      quantifiable fluorescent derivatives. All types of conjugated glycans were well
      recognized by appropriate CBPs. Thus, GDAP derivatives provide versatile new
      tools for biologists to quantify and covalently capture minute quantities of
      glycans for exploring their structures and functions and generating new glycan
      arrays from naturally occurring glycans.

PMID- 16278656
TI  - Evanescent-field fluorescence-assisted lectin microarray: a new strategy for
      glycan profiling.
AB  - Glycans have important roles in living organisms with their structural diversity.
      Thus, glycomics, especially aspects involving the assignment of functional
      glycans in a high-throughput manner, has been an emerging field in the
      postproteomics era. To date, however, there has been no versatile method for
      glycan profiling. Here we describe a new microarray procedure based on an
      evanescent-field fluorescence-detection principle, which allows sensitive, real
      time observation of multiple lectin-carbohydrate interactions under equilibrium
      conditions. The method allows quantitative detection of even weak lectin
      carbohydrate interactions (dissociation constant, K(d) > 10(-6) M) as fluorescent
      signals for 39 immobilized lectins. We derived fully specific signal patterns for
      various Cy3-labeled glycoproteins, glycopeptides and tetramethylrhodamine (TMR)
      labeled oligosaccharides. The obtained results were consistent with the previous
      reports of glycoprotein and lectin specificities. We investigated the latter
      aspects in detail by frontal affinity chromatography, another profiling method.
      Thus, the developed lectin microarray should contribute to creation of a new
      paradigm for glycomics.

PMID- 16278657
TI  - Correlative microscopy and electron tomography of GFP through photooxidation.
AB  - We have developed a simple correlative photooxidation method that allows for the
      direct ultrastructural visualization of the green fluorescent protein (GFP) upon
      illumination. The method, termed GRAB for GFP recognition after bleaching, uses
      oxygen radicals generated during the GFP bleaching process to photooxidize 3,3'
      diaminobenzidine (DAB) into an electron-dense precipitate that can be visualized
      by routine electron microscopy and electron tomography. The amount of DAB product
      produced by the GRAB method appears to be linear with the initial fluorescence,
      and the resulting images are of sufficient quality to reveal detailed spatial
      information. This is exemplified by the observed intra-Golgi stack and
      intracisternal distribution of a human Golgi resident glycosylation enzyme, N
      acetylgalactosaminyltransferase-2 fused either to enhanced GFP or CFP.

PMID- 16278658
TI  - Liquid-based free-flow electrophoresis-reversed-phase HPLC: a proteomic tool.

PMID- 16278660
TI  - Phase II study of gemcitabine and cisplatin in locally advanced/metastatic
      oesophageal cancer.
AB  - Palliative chemotherapy for inoperable/metastatic oesophageal cancer has limited
      activity. This study assesses the feasibility and activity of gemcitabine and
      cisplatin in this group of patients. In total, 42 patients with locally
      advanced/metastatic squamous or adenocarcinoma of the oesophagus were treated
      with gemcitabine 1250 mg m(-2) days 1 and 8 and cisplatin 75 mg m(-2) day 1 in a
      21-day cycle. Interim safety analysis was carried out after the first 19 patients
      suggested significant toxicity. The dose of gemcitabine was subsequently reduced
      to 1000 mg m(-2). Patients were assessed for toxicity and response. The median
      number of treatment cycles per patient was 4 (range 1-6). Grade 3-4 neutropenia
      occurred in 37% of cycles; however, there was only one episode of neutropenic
      fever. Nonhaematological toxicities included fatigue, nausea and vomiting. Among
      32 patients eligible for response, there were three complete responses and 16
      partial responses (overall response rate of 45%); nine patients had stable
      disease. Median survival was 11 months. The response rate appears to be greatest
      in those with squamous carcinoma compared to adenocarcinoma (71 vs 33%, P=0.036).
      The combination of gemcitabine and cisplatin in this schedule has manageable
      toxicity and significant activity in patients with locally advanced/metastatic
      oesophageal cancer and is worthy of further study.

PMID- 16278661
TI  - O6-(4-bromothenyl)guanine reverses temozolomide resistance in human breast tumour
      MCF-7 cells and xenografts.
AB  - Tumour resistance to chemotherapy involving methylating agents such as DTIC
      (dacarbazine) and temozolomide is linked to expression of the DNA repair protein
      O(6)-alkylguanine-DNA alkyltransferase (MGMT). There is considerable interest in
      improving the efficacy of such O(6)-alkylating chemotherapy by the prior
      inactivation of MGMT. We have examined the effect of the modified guanine base,
      O(6)-(4-bromothenyl)guanine (PaTrin-2, Patrin, Lomeguatrib) on MGMT activity and
      cell or xenograft tumour growth inhibition by temozolomide in the human breast
      carcinosarcoma cell line, MCF-7. PaTrin-2 effectively inactivated MGMT in MCF-7
      cells (IC(50) approximately 6 nM) and in xenografts there was complete
      inactivation of MGMT within 2 h of dosing (20 mg kg(-1) i.p.) and only slight
      recovery by 24 h. MGMT inactivation in a range of murine host tissues varied
      between complete and approximately 60%, with extensive recovery by 24 h. PaTrin-2
      (10 microM) substantially increased the growth inhibitory effects of temozolomide
      in MCF-7 cells (D(60)=10 microM with PaTrin-2 vs 400 microM without). In MCF-7
      xenografts, neither temozolomide (100 mg kg(-1) day(-1) for 5 days) nor PaTrin-2
      (20 mg kg(-1) day(-1) for 5 days) had any significant effect on tumour growth. In
      contrast, the PaTrin-2-temozolomide combination produced a substantial tumour
      growth delay: median tumour quintupling time was increase by 22 days (P<0.005)
      without any significant increase in toxicity as assessed from animal weight. A
      PaTrin-2-temozolomide combination may therefore be beneficial in the treatment of
      human breast cancers.

PMID- 16278662
TI  - Quantitative genetics: similar strokes for different folks.

PMID- 16278663
TI  - Genetic and epigenetic changes in the development of multiple colorectal cancers
      in the general population.

PMID- 16278664
TI  - Ectodomain shedding of the hypoxia-induced carbonic anhydrase IX is a
      metalloprotease-dependent process regulated by TACE/ADAM17.
AB  - Carbonic anhydrase IX (CA IX) is a transmembrane protein whose expression is
      strongly induced by hypoxia in a broad spectrum of human tumours. It is a highly
      active enzyme functionally involved in both pH control and cell adhesion. Its
      presence in tumours usually indicates poor prognosis. Ectodomain of CA IX is
      detectable in the culture medium and body fluids of cancer patients, but the
      mechanism of its shedding has not been thoroughly investigated. Here, we analysed
      several cell lines with natural and ectopic expression of CA IX to show that its
      ectodomain release is sensitive to metalloprotease inhibitor batimastat (BB-94)
      and that hypoxia maintains the normal rate of basal shedding, thus leading to
      concomitant increase in cell-associated and extracellular CA IX levels. Using CHO
      M2 cells defective in shedding, we demonstrated that the basal CA IX ectodomain
      release does not require a functional TNFalpha-converting enzyme (TACE/ADAM17),
      whereas the activation of CA IX shedding by both phorbol-12-myristate-13-acetate
      and pervanadate is TACE-dependent. Our results suggest that the cleavage of CA IX
      ectodomain is a regulated process that responds to physiological factors and
      signal transduction stimuli and may therefore contribute to adaptive changes in
      the protein composition of tumour cells and their microenvironment.

PMID- 16278665
TI  - Surrogate markers and survival in women receiving first-line combination
      anthracycline chemotherapy for advanced breast cancer.
AB  - Surrogate markers may help predict the effects of first-line treatment on
      survival. This metaregression analysis examines the relationship between several
      surrogate markers and survival in women with advanced breast cancer after
      receiving first-line combination anthracycline chemotherapy 5-fluorouracil,
      adriamycin and cyclophosphamide (FAC) or 5-fluorouracil, epirubicin and
      cyclophosphamide (FEC). From a systematic literature review, we identified 42
      randomised trials. The surrogate markers were complete or partial tumour
      response, progressive disease and time to progression. The treatment effect on
      survival was quantified by the hazard ratio. The treatment effect on each
      surrogate marker was quantified by the odds ratio (or ratio of median time to
      progression). The relationship between survival and each surrogate marker was
      assessed by a weighted linear regression of the hazard ratio against the odds
      ratio. There was a significant linear association between survival and complete
      or partial tumour response (P<0.001, R(2)=34%), complete tumour response (P=0.02,
      R(2)=12%), progressive disease (P<0.001, R(2)=38%) and time to progression
      (P<0.0001, R(2)=56%); R(2) is the proportion of the variability in the treatment
      effect on survival that is explained by the treatment effect on the surrogate
      marker. Time to progression may be a useful surrogate marker for predicting
      survival in women receiving first-line anthracycline chemotherapy and could be
      used to estimate the survival benefit in future trials of first-line chemotherapy
      compared to FAC or FEC. The other markers, tumour response and progressive
      disease, were less good.

PMID- 16278666
TI  - Upregulation of calcium-sensing receptor and mitogen-activated protein kinase
      signalling in the regulation of growth and differentiation in colon carcinoma.
AB  - In the present study, we demonstrate that Ca2+-induced growth inhibition and
      induction of differentiation in a line of human colon carcinoma cells (CBS) is
      dependent on mitogen-activated protein (MAP) kinase signaling and is associated
      with upregulation of extracellular calcium-sensing receptor (CaSR) expression.
      When CBS cells were grown in Ca2+-free medium and then switched to medium
      supplemented with 1.4 mM Ca2+, proliferation was reduced and morphologic features
      of differentiation were expressed. E-cadherin, which was minimally expressed in
      nonsupplemented medium, was rapidly induced in response to Ca2+ stimulation.
      Sustained activation of the extracellular signal-regulated kinase (ERK) occurred
      in Ca2+-supplemented medium. When an inhibitor of ERK activation (10 microM
      U0126) was included in the Ca2+-supplemented culture medium, ERK-activation did
      not occur. Concomitantly, E-cadherin was not induced, cell proliferation remained
      high and differentiation was not observed. The same level of Ca2+ supplementation
      that induced MAP kinase activation also stimulated CaSR upregulation in CBS
      cells. A clonal isolate of the CBS line that did not upregulate CaSR expression
      in response to extracellular Ca2+ was isolated from the parent cells. This
      isolate failed to produce E-cadherin or undergo growth inhibition/induction of
      differentiation when exposed to Ca2+ in the culture medium. However, ERK
      activation occurred as efficiently in this isolate as in parent CBS cells or in a
      cloned isolate that underwent growth reduction and differentiation in response to
      Ca2+ stimulation. Together, these data indicate that CaSR upregulation and MAP
      kinase signalling are both intermediates in the control of colon carcinoma cell
      growth and differentiation. They appear to function, at least in part,
      independently of one another.

PMID- 16278667
TI  - Activation of nuclear factor-kappaB in human prostate carcinogenesis and
      association to biochemical relapse.
AB  - Nuclear factor (NF)-kappaB/p65 regulates the transcription of a wide variety of
      genes involved in cell survival, invasion and metastasis. We characterised by
      immunohistochemistry the expression of NF-kappaB/p65 protein in six
      histologically normal prostate, 13 high-grade prostatic intraepithelial neoplasia
      (PIN) and 86 prostate adenocarcinoma specimens. Nuclear localisation of p65 was
      used as a measure of NF-kappaB active state. Nuclear localisation of NF-kappaB
      was only seen in scattered basal cells in normal prostate glands. Prostatic
      intraepithelial neoplasias exhibited diffuse and strong cytoplasmic staining but
      no nuclear staining. In prostate adenocarcinomas, cytoplasmic NF-kappaB was
      detected in 57 (66.3%) specimens, and nuclear NF-kappaB (activated) in 47
      (54.7%). Nuclear and cytoplasmic NF-kappaB staining was not correlated (P=0.19).
      By univariate analysis, nuclear localisation of NF-kappaB was associated with
      biochemical relapse (P=0.0009; log-rank test) while cytoplasmic expression did
      not. On multivariate analysis, serum preoperative prostate specific antigen
      (P=0.02), Gleason score (P=0.03) and nuclear NF-kappaB (P=0.002) were independent
      predictors of biochemical relapse. These results provide novel evidence for NF
      kappaB/p65 nuclear translocation in the transition from PIN to prostate cancer.
      Our findings also indicate that nuclear localisation of NF-kappaB is an
      independent prognostic factor of biochemical relapse in prostate cancer.

PMID- 16278668
TI  - Spread of human cancer cells occurs with probabilities indicative of a nongenetic
      mechanism.
AB  - There has been much uncertainty as to whether metastasis requires mutation at the
      time of spread. Here, we use clinical data to calculate the probability of the
      spread of melanoma and breast cancer cells. These calculations reveal that the
      probability of the spread of cancer cells is relatively high for small tumours
      (approximately 1 event of spread for every 500 cells for melanomas of 0.1 mm) and
      declines as tumours increase in size (approximately 1 event of spread for every
      10(8) cells for melanomas of 12 mm). The probability of spread of breast cancer
      cells from the lymph nodes to the periphery is approximately 1 event of spread
      for every 10(8) cells in the nodal masses, which have a mean diameter of 5 mm,
      while the probability of spread of cancer cells from the breast to the periphery
      when the primary masses are 5 mm is also approximately 1 event of spread for
      every 10(8) cells. Thus, the occurrence of an event of spread from the breast to
      the lymph nodes appears not to increase the propensity of the progeny of those
      cells to spread from the lymph nodes to the periphery. These values indicate that
      the spread of human breast cancer and melanoma cells is unlikely to occur by a
      mechanism requiring mutation at the time of spread.

PMID- 16278669
TI  - DNA replication licensing and cell cycle kinetics of normal and neoplastic
      breast.
AB  - Mcm2-7 (MCM) proteins are part of the origin licensing machinery that regulates
      initiation of DNA replication. Geminin is a licensing repressor and prevents
      reinitiation of DNA replication during S-G2-M phase by blocking reloading of Mcm2
      7 at replication origins. Here, we have analysed these replication licensing
      factors (RLFs) to determine whether the pathway becomes deregulated during
      mammary carcinogenesis, and have assessed their potential value as prognostic
      markers. Protein expression profiles were generated for Ki67, Mcm2, geminin, HER
      2, ER and PR in a series of reduction mammoplasty (n=18) and breast cancer
      specimens (n=120), and compared to clinicopathological parameters. A large
      proportion of epithelial cells of the terminal duct lobular unit reside in a
      primed 'replication licensed' but not proliferating state. This state is
      characterised by Mcm2 expression and absence of Ki67 and the S/G2/M marker
      geminin. In breast cancers, increasing tumour grade is associated with increased
      Ki67, Mcm2 and geminin expression. The Mcm2/Ki67 ratio decreases through the
      grades, indicating a shift from a predominantly licensed state to an actively
      proliferating state. This shift is associated with an increase in the
      geminin/Ki67 ratio, signifying a shortening of G1 phase in breast cancer cells.
      Ki67, Mcm2 and the Mcm2/Ki67 ratio are statistically significantly associated
      with the Nottingham Prognostic Index (NPI), but geminin and the geminin/Ki67
      ratio are not. Ki67, Mcm2 and Mcm2/Ki67 are highly correlated with one another,
      with Mcm2 being the single most important predictor of NPI score (P<0.001).
      However, only 12% of variation in NPI is explained by Mcm2, as the labelling
      index for this marker is approaching 100% for many of the high-grade tumours. The
      origin licensing phenotypes of normal breast and breast cancers therefore relate
      to their cellular differentiation status, and high-level MCM expression in more
      poorly differentiated tumours severely constrains their use as prognostic markers
      in breast cancer.

PMID- 16278671
TI  - The effect of Hus1 on ionizing radiation sensitivity is associated with
      homologous recombination repair but is independent of nonhomologous end-joining.
AB  - Mammalian Hus1 plays an important role in maintaining genomic integrity. Cells
      lacking mouse Hus1 are hypersensitive to DNA damage inducers including UV and
      camptothecin (CPT). By using clonogenic assay, we show here that Hus1 deficient
      mouse cells are hypersensitive to ionizing radiation (IR) compared with their
      Hus1-positive counterparts. However, these cells show similar induction levels
      and similar rejoining rates of DNA double strand breaks (DSBs) following IR,
      indicating that the effect of Hus1 on cell radiosensitivity is independent of
      nonhomologous end-joining (NHEJ). By combining an I-SceI-induced-DNA DSBs system
      and a siRNA approach, we also show that knocking down Hus1 decreases the
      efficiency of homologous recombination repair (HRR), which is associated with the
      cellular sensitivity to IR-induced killing. Together, these results indicate that
      the role of Hus1 affecting the sensitivity of cells to IR-induced killing is
      independent of NHEJ but might be linked to HRR.

PMID- 16278670
TI  - Stabilization of prolactin receptor in breast cancer cells.
AB  - The role of the hormone prolactin (PRL) in the pathogenesis of breast cancer is
      mediated by its cognate receptor (PRLr). Ubiquitin-dependent degradation of the
      PRLr that negatively regulates PRL signaling is triggered by PRL-mediated
      phosphorylation of PRLr on Ser349 followed by the recruitment of the beta
      transducin repeats-containing protein (beta-TrCP) ubiquitin-protein isopeptide
      ligase. We report here for the first time that interaction between PRLr and beta
      TrCP is less efficient in human breast cancer cells than in non-tumorigenic human
      mammary epithelial cells. Furthermore, we demonstrate that both PRLr degradation
      and PRLr phosphorylation on Ser349 are impaired in breast tumor cells and
      tissues, an observation that directly correlates with enhanced expression of the
      PRLr in malignant breast epithelium. These findings represent a novel mechanism
      through which altered PRLr stability may directly influence the pathogenesis of
      breast cancer.

PMID- 16278672
TI  - Deregulation of homologous recombination DNA repair in alkylating agent-treated
      stem cell clones: a possible role in the aetiology of chemotherapy-induced
      leukaemia.
AB  - Chemotherapeutic regimes involving alkylating agents, such as methylators and
      crosslinking nitrogen mustards, represent a major risk factor for acute myeloid
      leukaemia. A high frequency of microsatellite instability and evidence of MSH2
      loss in alkylating chemotherapy-related acute myeloid leukaemia (t-AML) suggests
      that DNA mismatch repair (MMR) dysfunction may be an initiating event in disease
      evolution. Subsequent accumulation of secondary genetic changes as a result of
      DNA MMR loss may ultimately lead to the gross chromosomal abnormalities seen in t
      AML. Homologous recombination repair (HRR) maintains chromosomal stability by the
      repair of DNA double-strand breaks, and is therefore a possible target for
      deregulation in MMR dysfunctional t-AML. In order to test this hypothesis Msh2-
      proficient and -deficient murine embryonic stem (ES) cells were used to examine
      the effects of MMR status and methylating agent treatment on cellular expression
      of DNA double-strand break repair genes. HRR gene expression was significantly
      deregulated in Msh2 null ES cell clones compared to wild-type clones.
      Furthermore, some Msh2 null clones expressed high levels of Rad51 specifically, a
      critical component of HRR. Such Rad51 superexpressing clones were also observed
      when expression was determined in monocytic myeloid cells differentiated from ES
      cells. A deregulated HRR phenotype could be partially recapitulated in MMR
      competent wild-type cells by treatment with the methylating agent, N-methyl-N
      nitrosourea. Furthermore, treatment with melphalan, a leukaemogenic DNA
      crosslinking chemotherapy nitrogen mustard predicted to elicit HRR, selected
      against cells with deregulated HRR. These data suggest a t-AML mechanism whereby
      DNA MMR loss promotes the emergence of HRR gene superexpressing clones, with
      concomitant chromosomal instability. However, melphalan selection against clones
      with deregulated HRR suggests that persistence and expansion of unstable clones
      may require additional genetic alterations that promote cell survival.

PMID- 16278673
TI  - Accelerated onsets of gastric hamartomas and hepatic adenomas/carcinomas in
      Lkb1+/-p53-/- compound mutant mice.
AB  - Germline mutations in the LKB1 gene are responsible for Peutz-Jeghers syndrome
      (PJS), which is characterized by gastrointestinal hamartomas and increasing risk
      of cancer. Mice with Lkb1(+/-) mutation develop gastric hamartomas after >20
      weeks of age, and hepatocellular adenomas and carcinomas >30 weeks. It has been
      reported that, in PJS patients, carcinomas progressed from hamartomas contain p53
      mutations, and that LKB1 regulates p53-dependent apoptosis. To investigate the
      roles of LKB1 and p53 mutations in tumorigenesis, we constructed compound mutant
      mice of Lkb1 and p53 genes. In the Lkb1(+/-)p53(-/-) mice, formation of gastric
      hamartomas and hepatic tumors was accelerated. However, histopathology of
      hamartomas was similar between Lkb1(+/-)p53(-/-) and Lkb1(+/-) mice, and Lkb1
      genotype remained heterozygous, suggesting that the p53 mutation affected
      hamartoma initiation. Contrary to the heterozygous hamartomas in the stomach and
      duodenum, the hepatic adenomas in Lkb1(+/-)p53(-/-) mice showed loss of Lkb1
      heterozygosity (LOH), suggesting that lack of p53 stimulated Lkb1 LOH and tumor
      initiation in the liver. Taken together, these results indicate that lack of p53
      causes earlier onsets of gastric hamartomas and hepatic tumors in Lkb1(+/-)p53(-/
      ) mice.

PMID- 16278674
TI  - Physical interaction of apoptosis-inducing factor with DNA and RNA.
AB  - Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein, which upon
      apoptosis induction translocates to the nucleus where it interacts with DNA by
      virtue of positive charges clustered on the AIF surface. Here we show that the
      AIF interactome, as determined by mass spectroscopy, contains a large panel of
      ribonucleoproteins, which apparently bind to AIF through the RNA moiety. However,
      AIF is devoid of any detectable RNAse activity both in vitro and in vivo.
      Recombinant AIF can directly bind to DNA as well as to RNA. This binding can be
      visualized by electron microscopy, revealing that AIF can condense DNA, showing a
      preferential binding to single-stranded over double-stranded DNA. AIF also binds
      and aggregates single-stranded and structured RNA in vitro. Single-stranded poly
      A, poly G and poly C, as well double-stranded A/T and G/C RNA competed with DNA
      for AIF binding with a similar efficiency, thus corroborating a computer
      calculated molecular model in which the binding site within AIF is the same for
      distinct nucleic acid species, without a clear sequence specificity. Among the
      preferred electron donors and acceptors of AIF, nicotine adenine dinucleotide
      phosphate (NADP) was particularly efficient in enhancing the generation of higher
      order AIF/DNA and AIF/RNA complexes. Altogether, these data support a model in
      which a direct interaction of AIF contributes to the compaction of nucleic acids
      within apoptotic cells.

PMID- 16278675
TI  - Stable gene silencing of cyclin B1 in tumor cells increases susceptibility to
      taxol and leads to growth arrest in vivo.
AB  - Cyclin B1 is the regulatory subunit of cyclin-dependent kinase 1 (Cdk1) and is
      critical for the initiation of mitosis. Accumulating data indicate that the
      deregulation of cyclin B1 is tightly linked to neoplastic transformation. To
      study the phenotype and the potential preclinical relevance, we generated HeLa
      cell lines stably transfected with the plasmids encompassing short hairpin RNA
      (shRNA) targeting cyclin B1. We demonstrate that the reduction of cyclin B1
      caused inhibition of proliferation by arresting cells in G2 phase and by inducing
      apoptosis. Cells, entering mitosis, were impaired in chromosome condensation and
      alignment. Importantly, HeLa cells with reduced cyclin B1 were more susceptible
      to the treatment of small interfering RNA targeting Polo-like kinase 1 (Plk1) and
      to the administration of the chemotherapeutic agent taxol. Finally, HeLa cells
      with reduced cyclin B1 showed inhibited tumor growth in nude mice compared to
      that of control cells. In summary, our data indicate that cyclin B1 is an
      essential molecule for tumor cell survival and aggressive proliferation,
      suggesting that the downregulation of cyclin B1, especially in combination with
      other molecular targets, might become an interesting strategy for antitumor
      intervention.

PMID- 16278676
TI  - Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human
      renal cell carcinoma.
AB  - Epigenetic alterations like DNA methylation and the resulting inactivation of
      cancer-related genes often contribute to the development of various cancers. To
      identify the genes that are silenced by aberrant methylation in renal cell
      carcinoma (RCC), we subjected two RCC lines to methylated CpG island
      amplification/representational difference analysis. This identified 27 CpG
      islands. Combined bisulfite restriction analysis of these CpG islands in primary
      RCC cases revealed that four were methylated in a tumor-specific manner. One of
      these was identified as the human homeo-box gene B13 (HOXB13) gene, but the
      remaining three CpG islands were not associated with known genes. The methylation
      frequencies of HOXB13 in primary RCC samples and lines were 30 and 73%,
      respectively. The methylation status of HOXB13 correlated with the loss of its
      expression both in RCC lines and primary tumors, and methyltransferase inhibitor
      treatment induced the recovery of its expression. Exogenous expression of HOXB13
      in RCC cells that lacked endogenous HOXB13 expression suppressed colony formation
      and induced apoptotic features. Furthermore, HOXB13 methylation correlated
      positively with tumor grade and microvessel invasion. These results suggest that
      HOXB13 is a novel candidate tumor suppressor gene in RCC and that its
      inactivation may play an important role in both RCC tumorigenesis and
      progression.

PMID- 16278677
TI  - Elevated levels of ornithine decarboxylase cooperate with Raf/ERK activation to
      convert normal keratinocytes into invasive malignant cells.
AB  - Ornithine decarboxylase (ODC) overexpression coupled with activated Ras is fully
      sufficient to oncogenically transform primary keratinocytes. To determine the Ras
      effector pathways that represent the minimal essential contribution to full
      oncogenic transformation in this context, we evaluated the cooperativity of
      different Ras effector mutants with overexpressed ODC in an in vivo tracheal
      xenotransplantation assay for epithelial cell invasiveness. Primary
      keratinocytes, isolated from either K6/ODC transgenic mouse skin (expressing
      increased ODC) or from normal littermate skin were infected with retrovirus
      producing an activated RasV12 or partial loss-of-function effector mutants of
      RasV12 that selectively induce only the Raf/ERK, RalGDS, or the PI3-kinase
      signaling pathway. Whereas keratinocytes expressing a fully activated RasV12 are
      not invasive in tracheal xenotransplants, ODC-overexpressing keratinocytes
      acquire an invasive phenotype with additional expression of either RasV12 or
      activation of the Raf/ERK pathway. Independent of a mutated ras, elevated levels
      of ODC activate the Akt/mTOR signaling pathway as well as the Rho/Rac pathway in
      primary keratinocytes. Thus, Raf/ERK signaling is sufficient to cooperate with
      increased ODC activity in the conversion of normal keratinocytes to invasive
      cells. In order to promote invasiveness in keratinocytes, elevated levels of ODC
      may cooperate with Raf/ERK via activation of the Akt and Rho/Rac signaling
      pathway.

PMID- 16278678
TI  - Ha-ras(val12) induces HSP70b transcription via the HSE/HSF1 system, but HSP70b
      expression is suppressed in Ha-ras(val12)-transformed cells.
AB  - Heat shock proteins (Hsps) are overexpressed in many tumors, but are
      downregulated in some tumors. To check for a direct effect of Ha-Ras(val12) on
      HSP70 transcription, we transiently expressed the oncoprotein in Rat1 fibroblasts
      and monitored its effect on HSP70b promoter-driven reporter gene. We show that
      expression of Ha-Ras(val12) induced this promoter. Promoter analysis via
      systematic deletions and point mutations revealed that Ha-Ras(val12) induces
      HSP70b transcription via heat shock elements (HSEs). Also, Ha-Ras(val12)
      induction of HSE-mediated transcription was dramatically reduced in HSF1-/-
      cells. Yet, residual effect of Ha-Ras(val12) that was still measured in HSF1-/-
      cells suggests that some of the Ha-Ras(val12) effect is Hsf1-independent. When
      HSF1-/- cells, stably expressing Ha-Ras(val12), were grown on soft agar only
      small colonies were formed suggesting a role for heat shock factor 1 (Hsf1) in Ha
      Ras(val12)-mediated transformation. Although Ha-ras(Val12) seems to be an inducer
      of HSP70's expression, we found that in Ha-ras(Val12-)transformed fibroblasts
      expression of this gene is suppressed. This suppression is correlated with higher
      sensitivity of Ha-ras(val12)-transformed cells to heat shock. We suggest that Ha
      ras(Val12) is involved in Hsf1 activation, thereby inducing the cellular
      protective response. Cells that repress this response are perhaps those that
      acquire the capability to further proliferate and become transformed clones.

PMID- 16278680
TI  - CITED1 homozygous null mice display aberrant pubertal mammary ductal
      morphogenesis.
AB  - Expression microarray analysis identified CITED1 among a group of genes
      specifically upregulated in the pubertal mouse mammary gland. At puberty, CITED1
      localizes to the luminal epithelial cell population of the mammary ducts and the
      body cells of the terminal end buds. Generation of CITED1 gene knockout mice
      showed that homozygous null mutants exhibit retarded mammary ductal growth at
      puberty and, in addition, dilated ductal structures with a lack of spatial
      restriction of the subtending branches. Analysis of CITED1 homozygous null and
      heterozygous null mammary gland gene expression using microarrays suggested that
      the mammary-specific phenotype seen in the homozygous null females is due to a
      disturbance in the transcription of a number of key mediators of pubertal ductal
      morphogenesis. These include estrogen and TGFbeta responsive genes, such as the
      EGFR/ErbB2 ligand, amphiregulin, whose transcription we suggest is directly or
      indirectly regulated by CITED1.

PMID- 16278681
TI  - CRIPak, a novel endogenous Pak1 inhibitor.
AB  - p21-activated protein kinase 1 (Pak1) plays an important role in several cellular
      processes, including cytoskeleton reorganization, promotion of the cell survival,
      and the estrogen receptor (ER) signaling. Pak1 expression and activity is
      deregulated in a number of cancers. Pak1 is activated by a variety of
      physiological signals; however, less is known about the negative regulators of
      Pak1. Here, we report a negative regulator of Pak1. By performing a yeast two
      hybrid screen of a mammary gland library, we identified cysteine-rich inhibitor
      of Pak1 (CRIPak) as a novel Pak1-interacting protein. We found that CRIPak is an
      intronless gene that localized to chromosome 4p16.3. It contains 13 zinc-finger
      domains and has three trypsin inhibitor-like, cysteine-rich domains and is widely
      expressed in a number of human cells and tissues. We further found that CRIPak
      interacted with Pak1 through the N-terminal regulatory domain and inhibited Pak1
      kinase in both in vitro and in vivo assays. CRIPak inhibited Pak1-mediated LIM
      kinase activation and enhancement of ER transactivation. Conversely, selective
      inhibition of the endogenous CRIPak resulted in an increased Pak1 activity, and
      consequently, increased cytoskeleton remodeling and Pak1-mediated ER
      transactivation activity. The hormonal stimulation of cells enhanced CRIPak
      expression and promoted its colocalization with ER in the nuclear compartment.
      Our findings suggest that CRIPak is a novel negative regulator of the Pak1 and
      has a role in the modulation of Pak1-mediated ER transactivation in breast cancer
      cells.

PMID- 16278679
TI  - Mitochondrial DNA determines androgen dependence in prostate cancer cell lines.
AB  - Prostate cancer progresses from an androgen-dependent to androgen-independent
      stage after androgen ablation therapy. Mitochondrial DNA plays a role in cell
      death and metastatic competence. Further, heteroplasmic large-deletion
      mitochondrial DNA is very common in prostate cancer. To investigate the role of
      mitochondrial DNA in androgen dependence of prostate cancers, we tested the
      changes of normal and deleted mitochondrial DNA in accordance with the
      progression of prostate cancer. We demonstrated that the androgen-independent
      cell line C4-2, established by inoculation of the androgen-dependent LNCaP cell
      line into castrated mice, has a greatly reduced amount of normal mitochondrial
      DNA and an accumulation of large-deletion DNA. Strikingly, the depletion of
      mitochondrial DNA from androgen-dependent LNCaP resulted in a loss of androgen
      dependence. Reconstitution of normal mitochondrial DNA to the mitochondrial DNA
      depleted clone restored androgen dependence. These results indicate that
      mitochondrial DNA determines androgen dependence of prostate cancer cell lines.
      Further, mitochondrial DNA-deficient cells formed tumors in castrated athymic
      mice, whereas LNCaP did not. The accumulation of large deletion and depletion of
      mitochondrial DNA may thus play a role in the development of androgen
      independence, leading to progression of prostate cancers.

PMID- 16278682
TI  - Loss of one HuD allele on chromosome #1p selects for amplification of the N-myc
      proto-oncogene in human neuroblastoma cells.
AB  - In human neuroblastoma tumors, amplification of the N-myc proto-oncogene and loss
      of all or part of the short arm of chromosome #1 are both associated with a poor
      prognosis. Accruing evidence indicates that it is the absence of one allele of
      the HuD (ELAVL4) gene, encoding the neuronal-specific RNA-binding protein HuD and
      localized to 1p34, that is linked to amplification. In 12 human neuroblastoma
      cell lines, N-myc amplification correlates with loss of one HuD allele and
      decreased HuD expression. Transfection experiments demonstrate that modulating
      HuD expression affects N-myc gene copy number as well as expression. Introduction
      of a sense HuD construct into two N-myc amplified cell lines considerably
      increases N-myc expression whereas gene copy number decreases. Conversely,
      expression of antisense HuD in N-myc nonamplified SH-SY5Y cells reduces HuD and N
      myc mRNA levels even as cells show amplification of the N-myc gene. Thus, N-myc
      gene copy number is modulated by alteration of HuD expression. We propose that
      haploinsufficiency of HuD due to chromosome #1p deletion in neuroblastoma selects
      for cells that amplify N-myc genes. Application of these findings could lead to
      more effective therapies in the treatment of those patients with the worst
      prognosis.

PMID- 16278683
TI  - p53 tumor suppressor protein regulates the levels of huntingtin gene expression.
AB  - The p53 protein is a transcription factor that integrates various cellular stress
      signals. The accumulation of the mutant huntingtin protein with an expanded
      polyglutamine tract plays a central role in the pathology of human Huntington's
      disease. We found that the huntingtin gene contains multiple putative p53
      responsive elements and p53 binds to these elements both in vivo and in vitro.
      p53 activation in cultured human cells, either by a temperature-sensitive mutant
      p53 protein or by gamma-irradiation (gamma-irradiation), increases huntingtin
      mRNA and protein expression. Similarly, murine huntingtin also contains multiple
      putative p53-responsive elements and its expression is induced by p53 activation
      in cultured cells. Moreover, gamma-irradiation, which activates p53, increases
      huntingtin gene expression in the striatum and cortex of mouse brain, the major
      pathological sites for Huntington's disease, in p53+/+ but not the isogenic p53-/
      mice. These results demonstrate that p53 protein can regulate huntingtin
      expression at transcriptional level, and suggest that a p53 stress response could
      be a modulator of the process of Huntington's disease.

PMID- 16278685
TI  - LDL particle size, fat distribution and insulin resistance in obese children.
AB  - BACKGROUND: The importance of small dense low-density lipoprotein (sdLDL)
      cholesterol in coronary heart disease has been demonstrated in many studies. Body
      fat accumulation, especially abdominal adiposity, is one of the important factors
      modifying the expression of sdLDL in adults. OBJECTIVE: To determine the
      prevalence of sdLDL in obese children, and to investigate its relationship with
      anthropometric and metabolic variables. SUBJECTS: A total of 30 obese children
      (22 males, 8 females) aged 12.6+/-0.6 years (mean+/-s.e.), who presented to our
      outpatient clinic with obesity. METHODS: LDL peak particle diameter was
      determined using gel electrophoresis. LDL subclasses were classified into sdLDL
      (pattern B; diameter<25.5 nm) and non-sdLDL (pattern A; diameter>or=25.5 nm).
      Anthropometric and metabolic variables were also determined to identify factors
      modifying LDL particle size. RESULTS: sdLDL was detected in 11 children (40.0%).
      In children with sdLDL, waist/height ratio was significantly higher (P=0.0466),
      and they had significantly higher triglyceride (TG) (P=0.0035) and lower high
      density lipoprotein cholesterol (HDLC) levels (P=0.036). Peak LDL diameter as a
      continuous variable was significantly correlated with HDLC and TG levels. In
      multiple regression analysis, body mass index and waist/height ratio were
      significant determinants of the peak LDL diameter variability. CONCLUSIONS: We
      found a high prevalence of sdLDL in obese children, and a relationship of peak
      LDL diameter with abdominal fat accumulation, HDLC and TG levels. The presence of
      sdLDL might be an important risk factor for the metabolic syndrome.

PMID- 16278684
TI  - Glycogen synthase kinase-3 is a negative regulator of extracellular signal
      regulated kinase.
AB  - Glycogen-synthase kinase-3 (GSK-3) and extracellular signal-regulated kinase
      (ERK) are critical downstream signaling proteins for the PI3-kinase/Akt and
      Ras/Raf/MEK-1 pathway, respectively, and regulate diverse cellular processes
      including embryonic development, cell differentiation and apoptosis. Here, we
      show that inhibition of GSK-3 using GSK-3 inhibitors or RNA interference (RNAi)
      significantly induced the phosphorylation of ERK1/2 in human colon cancer cell
      lines HT29 and Caco-2. Pretreatment with the PKCdelta-selective inhibitor
      rottlerin or transfection with PKCdelta siRNA attenuated the phosphorylation of
      ERK1/2 induced by the GSK-3 inhibitor SB-216763 and, furthermore, treatment with
      SB-216763 or transfection with GSK-3alpha and GSK-3beta siRNA increased PKCdelta
      activity, thus identifying a role for PKCdelta in the induction of ERK1/2
      phosphorylation by GSK-3 inhibition. Treatment with SB-216763 increased
      expression of cyclooxygenase-2 (COX-2) and IL-8, which are downstream targets of
      ERK1/2 activation; this induction was abolished by MEK/ERK inhibition, suggesting
      GSK-3 inhibition induced COX-2 and IL-8 through ERK1/2 activation. The
      transcriptional induction of COX-2 and IL-8 by GSK-3 inhibition was further
      demonstrated by the increased COX-2 and IL-8 promoter activity after SB-216763
      treatment or transfection with GSK-3alpha or GSK-3beta siRNA. Importantly, our
      findings identify GSK-3, acting through PKCdelta, as a negative regulator of
      ERK1/2, thus revealing a novel crosstalk mechanism between these critical
      signaling pathways.

PMID- 16278686
TI  - Effects of docosahexaenoic acid supplementation on blood lipids, estrogen
      metabolism, and in vivo oxidative stress in postmenopausal vegetarian women.
AB  - BACKGROUND: Vegetarians are generally deficient in long-chain n-3 fatty acids.
      Long-chain n-3 fatty acids have a beneficial effect on plasma lipid levels, and
      some studies showed that they had breast cancer suppression effect. One of the
      biomarkers of breast cancer risk is the ratio of urinary 2-hydroxyestrone (2
      OHE(1)) to 16alpha-hydroxyestrone (16alpha-OHE(1)). OBJECTIVE: To investigate the
      effect of docosahexaenoic acid (DHA, 22:6n-3) supplementation on blood lipids,
      estrogen metabolism and oxidative stress in vegetarians. DESIGN: Single-blind,
      randomized, placebo-controlled trial. INTERVENTIONS: Twenty-seven postmenopausal
      vegetarian women were recruited. After a 2-week run-in period with 6 g placebo
      corn oil, the subjects were subsequently randomized to receive either 6 g corn
      oil (n=13) or 6 g DHA-rich algae oil (2.14 g of DHA/day) (n=14) for 6 weeks. Two
      subjects in corn oil group withdrew before completion. MAIN OUTCOME MEASURES:
      Plasma lipids, urinary 2-OHE(1) and 16alpha-OHE(1), urinary F(2)-isoprostanes and
      plasma alpha-tocopherol. RESULTS: Plasma LDL-DHA and EPA level increased
      significantly by DHA supplementation. DHA decreased plasma cholesterol (C) levels
      (P=0.04), but did not influence the levels of plasma TG, LDL-C and HDL-C, alpha
      tocopherol, urinary F(2)-isoprostanes, 2-OHE(1), 16alpha-OHE(1) and ratio of 2
      OHE(1) to 16alpha-OHE(1) as compared to corn oil. CONCLUSION: DHA supplementation
      at a dose of 2.14 g/day for 42 days decreases plasma cholesterol but neither does
      it show beneficial effects on estrogen metabolism, nor does it induce deleterious
      effects on the observed in vivo antioxidant or oxidative stress marker in
      postmenopausal vegetarian women. SPONSORSHIP: A grant (# DOH89-TD-1062) from
      Department of Health, Executive Yuan, Taiwan.

PMID- 16278687
TI  - The Florence diet is not Mediterranean. Really?

PMID- 16278688
TI  - Validity of overweight and obesity in a nation based on self-report versus
      measurement device data.
AB  - OBJECTIVE: To analyze overweight and obesity in a nation by self-report (SR) data
      and by data about the target person provided via other household members compared
      to measurement devices (MD). The magnitude of hypothesized under-reporting by the
      SR data should be estimated with adjustment for age, gender, and education.
      DESIGN: Two cross-sectional studies, nationally representative health examination
      surveys (response rates: 61.4 and 73.2%, respectively). SETTING: Adult general
      population of Germany aged 20-79 years. SUBJECTS: Sample 1 included 6806
      residents. Samples 2 (n=98 673) and 3 (n=34 960) included residents in the second
      survey. MEASUREMENTS: In sample 1 MD data were collected, in sample 2 SR data
      were collected, and in sample 3 body weight and height information was provided
      from another household member living together with the target person. RESULTS: MD
      data revealed higher proportions of overweight and obesity compared to SR. Among
      women with body mass index (BMI) 35.00 or higher, the odds ratio (OR) was 3.9
      (95% confidence interval, CI, 3.2-4.7), and among men 2.8 (CI, 2.2-3.6) for MD
      versus SR. Data from other household members also revealed higher proportions of
      overweight and obesity than SR (OR for BMI 35.00 or higher 2.1, CI, 1.7-2.5, for
      data from other household members versus SR in women and OR 1.3, CI, 1.1-1.5, in
      men). CONCLUSIONS: MD data should be used when providing proportions of
      overweight and obesity in a nation such as Germany.

PMID- 16278689
TI  - A critique of Truswell's A2 milk review.

PMID- 16278690
TI  - The relationship between folate and docosahexaenoic acid in men.
AB  - OBJECTIVE: Docosahexaenoic acid (DHA, 22:6n-3), an essential omega 3 fatty acid,
      may protect against disorders of emotional regulation as well as cardiovascular
      disease. Animal studies demonstrate that dietary folate can increase tissue
      concentrations of DHA, although the literature, to date, includes no human
      studies examining the possibility that folate status may affect plasma DHA
      concentrations. The objective of this study is to determine if the blood
      concentrations of folate and DHA are correlated in humans. DESIGN: Retrospective
      study. SETTING: An American research hospital. SUBJECTS: A total of 15 normal and
      22 hostile and aggressive subjects, with a mean age of 38 years. METHODS:
      Concentrations of plasma polyunsaturated essential fatty acids and red blood cell
      folate (RBC folate) were obtained prior to 1996, before American flour was
      enriched with folate. RESULTS: RBC folate was significantly correlated with
      plasma DHA, r=0.57, P=0.005 in the aggressive group. Age, smoking and alcohol
      consumption did not alter the results. No other essential fatty acids were
      significantly associated with RBC folate in either group. CONCLUSIONS: The
      positive relationship between plasma DHA and RBC folate concentrations suggests
      that these two nutrients should be examined together in order to make the most
      accurate inferences about their relative contributions to disease pathogenesis.
      Our findings present one explanation why some conditions associated with
      hostility and low DHA status, such as cardiovascular disease and emotional
      disorders, are also associated with low folate status. SPONSORSHIP: National
      Institutes of Health, National Institute on Alcohol Abuse and Alcoholism.

PMID- 16278691
TI  - Consumers' readiness to eat a plant-based diet.
AB  - OBJECTIVE: The aim of this study was to examine consumers' readiness to change to
      a plant-based diet. DESIGN: Mail survey that included questions on readiness to
      change, eating habits and perceived benefits and barriers to the consumption of a
      plant-based diet. SETTING: Victoria, Australia. SUBJECTS: A total of 415 randomly
      selected adults. RESULTS: In terms of their readiness to eat a plant-based diet,
      the majority (58%) of participants were in the precontemplation stage of change,
      while 14% were in contemplation/preparation, and 28% in action/maintenance. Those
      in the action/maintenance stage ate more fruit, vegetables, nuts, seeds, whole
      meal bread, and cooked cereals than those in earlier stages. There were
      statistically significant differences in age and vegetarian status between the
      stages of change, but not for other demographic variables. There were strong
      differences across the stages of change with regard to perceived benefits and
      barriers to plant-based diets. For example, those in action/maintenance scored
      highest for benefit factors associated with well-being, weight, health,
      convenience and finances, whereas those in the precontemplation stage did not
      recognise such benefits. CONCLUSIONS: These findings can be utilised to help
      provide appropriate nutrition education and advertising, targeted at specific
      stages of change. For example, education about how it is possible to obtain iron
      and protein from a plant-based diet and on the benefits of change, in addition to
      tips on how to make a gradual, easy transition to a plant-based diet, could help
      progress precontemplators to later stages. SPONSORSHIP: Australian Research
      Council.

PMID- 16278692
TI  - Pomegranate juice supplementation in chronic obstructive pulmonary disease: a 5
      week randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: The aim of the present study is to investigate the effect of
      antioxidant polyphenol-rich pomegranate juice (PJ) supplementation for 5 weeks on
      patients with stable chronic obstructive pulmonary disease (COPD), since the
      oxidative stress plays a major role in the evolution and pathophysiology of COPD.
      DESIGN: A randomized, double-blind, placebo-controlled trial was conducted.
      SUBJECTS: A total of 30 patients with stable COPD were randomly distributed in
      two groups (15 patients each). INTERVENTIONS: Both groups consumed either 400 ml
      PJ daily or matched placebo (synthetic orange-flavoured drink) for 5 weeks.
      Trolox Equivalent Antioxidant Capacity (TEAC) of PJ, blood parameters (14
      haematological and 18 serobiochemical), respiratory function variables,
      bioavailability of PJ polyphenols (plasma and urine) and urinary isoprostane (8
      iso-PGF(2alpha)) were evaluated. RESULTS: The daily dose of PJ (containing 2.66 g
      polyphenols) provided 4 mmol/l TEAC. None of the polyphenols present in PJ were
      detected in plasma or in urine of volunteers. The most abundant PJ polyphenols,
      ellagitannins, were metabolized by the colonic microflora of COPD patients to
      yield two major metabolites in both plasma and urine (dibenzopyranone
      derivatives) with no TEAC. No differences were found (P > 0.05) between PJ and
      placebo groups for any of the parameters evaluated (serobiochemical and
      haematological), urinary 8-iso-PGF(2alpha), respiratory function variables and
      clinical symptoms of COPD patients. CONCLUSIONS: Our results suggest that PJ
      supplementation adds no benefit to the current standard therapy in patients with
      stable COPD. The high TEAC of PJ cannot be extrapolated in vivo probably due to
      the metabolism of its polyphenols by the colonic microflora. The understanding of
      the different bioavailability of dietary polyphenols is critical before claiming
      any antioxidant-related health benefit. SPONSORSHIP: 'Fundacion Seneca' (Murcia,
      Spain), Project PB/18/FS/02 and Spanish CICYT, Project AGL2003-02195.

PMID- 16278694
TI  - Meal glycaemic load of normal-weight and overweight Hong Kong children.
AB  - OBJECTIVE: To describe the pattern of meal glycaemic load of children in Hong
      Kong and to determine whether the meal glycaemic load is associated with
      childhood overweight. METHOD: Dietary records (3-day) of 316 Hong Kong children
      aged 6-7 years were collected. Glycaemic load was calculated from the estimated
      weight (WT), carbohydrate content (%CHO) and glycaemic index (GI) of each food
      taken using the equation: (% CHO x GI x WT/100). The meal glycaemic load was then
      the sum of the glycaemic loads of all food taken in each meal. Logistic
      regression analyses were used to compare the average meal glycaemic load (of
      breakfast, lunch and dinner) and other dietary parameters between overweight
      children and normal-weight children. RESULTS: Breakfast, lunch, dinner and snacks
      provided, respectively, 17, 29, 29 and 25% of the total glycaemic load in a day.
      White rice (excluding congee (rice porridge) and glutinous rice) contributed
      almost half of the total glycaemic load. Adjusted logistic regression showed that
      the meal glycaemic load was not significantly associated with childhood
      overweight after adjusting for parental obesity, birth weight, sleeping duration,
      mean energy intake and paternal smoking. CONCLUSION: Meal glycaemic load
      calculated from current diet was not an independent factor associated with
      childhood overweight in children aged 6-7 years. Our data suggested that
      modifying the type of rice/staple consumed and choosing low-GI snacks could have
      a major influence on the total meal glycaemic load of young Hong Kong children.

PMID- 16278693
TI  - Prescreening tools for diabetes and obesity-associated dyslipidaemia: comparing
      BMI, waist and waist hip ratio. The D.E.S.I.R. Study.
AB  - OBJECTIVE: To compare the sensitivities of BMI, waist circumference and waist hip
      ratio (WHR) in identifying subjects who should be screened for diabetes and/or
      for obesity-associated dyslipidaemia. DESIGN: Cross-sectional study. SETTING:
      Central-western France. PARTICIPANTS: More than 3000 men and women, aged 40-64
      years, from the French study: data from an epidemiological study on the insulin
      resistance syndrome (D.E.S.I.R.). MAIN OUTCOME MEASURES: Sensitivity and
      specificity for screened diabetes (fasting plasma glucose>or=7.0 mmol/l) and
      screened dyslipidaemia (triglycerides>or=2.3 mmol/l and/or HDL-cholesterol
      <0.9/1.1 mmol/l (men/women)) according to BMI, waist circumference and WHR.
      RESULTS: Sensitivities increased as more corpulent subjects were screened, but
      they increased slowly after screening the top 30%: body mass index (BMI)>or=27/26
      kg/m(2) (men/women) or waist >or=96/83 cm or WHR>or=0.96/0.83. These values were
      chosen as thresholds. In men, BMI had a nonsignificantly higher sensitivity than
      waist or WHR for both diabetes and dyslipidaemia (77 vs 74 and 66% P<0.3, 0.09;
      56 vs 54 and 49% P<0.5, 0.16). For women, waist had a slightly higher sensitivity
      than BMI or WHR (82 vs 77 and 77% P<0.8, 0.7) for diabetes; for dyslipidaemia,
      waist and WHR had similar sensitivities, higher than for BMI (65 and 67 vs 54%
      P<0.16, 0.13). CONCLUSIONS: We propose that for screening in a French population
      40-64 years of age, the more obese 30% of the population, identified either by
      BMI, waist or WHR be screened for diabetes and obesity-associated dyslipidaemia.

PMID- 16278695
TI  - Relationship between birth weight and urea kinetics in children.
AB  - OBJECTIVE: To explore the effect of birth weight on urea kinetics in young
      healthy children. DESIGN: Observational study. SETTING: Tertiary center for
      treatment of malnutrition. SUBJECTS: A total of 17 male children, 6-24 months
      old, who had recovered from malnutrition. INTERVENTIONS: Urea kinetics were
      measured using stable isotope methodology with [(15)N(15)N]-urea over 36 h.
      RESULTS: Birth weight was negatively related to urea hydrolysis after controlling
      for the intake of protein (adjusted R (2 ) = 0.91, P = 0.001) and separately for
      energy intake (adjusted R (2) = 0.95, P = 0.001), age (adjusted R (2) = 0.90, P =
      0.001) and rate of weight gain (adjusted R (2) = 0.91, P = 0.001). There was a
      tendency for higher urea production in the children with lower birth weight after
      controlling for nitrogen intake (adjusted R (2) = 0.93, P = 0.099), and
      separately for age (adjusted R (2) = 0.94, P = 0.06) and rate of weight gain
      (adjusted (R (2) = 0.92, P = 0.096). Urea excretion was not significantly related
      to birth weight. CONCLUSIONS: The salvaging of urea nitrogen following urea
      hydrolysis contributed significantly more to the nitrogen economy in children
      with lower birth weight compared to those with higher birth weight. This may be
      as a result of reductive adaptation in the children with lower birth weight as a
      consequence of inappropriate prenatal nutrition and growth.

PMID- 16278696
TI  - Dietary patterns and their socio-demographic determinants in 10 European
      countries: data from the DAFNE databank.
AB  - OBJECTIVE: To describe the dietary patterns of 10 European countries and their
      socio-demographic determinants, using the comparable between-countries DAFNE
      data. DESIGN: Analysis of standardized and postharmonized data collected through
      the national household budget surveys. SETTING: Nationally representative surveys
      undertaken in 10 European countries, generally in the second half of the 1990s.
      RESULTS: The differences in the fruit and vegetable consumption previously
      identified between Mediterranean and Northern European countries seem to be
      leveling out, particularly in relation to fruit consumption. Pulses, however,
      still characterize the diet of the Mediterraneans. Straying from their
      traditional food choices, Mediterraneans recorded high availability of
      unprocessed red meat, while Central and Northern Europeans preferably consumed
      meat products. The household availability of beverages (alcoholic and non
      alcoholic) is generally higher among Central and Northern European populations.
      Principal component (PC) analysis led to the identification of two dietary
      patterns in each of the 10 countries. The first was similar in all countries and
      indicated 'wide-range' food buyers. The second was slightly more varied and
      described 'beverage and convenience' food buyers. PC1 was common among households
      of retired and elderly members, while PC2 was common among households located in
      urban or semi-urban areas and among adult Scandinavians living alone.
      CONCLUSIONS: The dietary patterns identified point towards a progressive
      narrowing of dietary differences between North and South European countries. The
      comparable between-countries DAFNE data could prove useful in ecological studies,
      in the formulation of dietary guidelines and public health initiatives addressing
      specific population groups. SPONSORSHIP: European Commission.

PMID- 16278697
TI  - Pharmacokinetic analysis of rapacuronium and its metabolite during liver
      transplantation: an assessment of its potential as a pharmacodynamic probe.
AB  - The liver extracts aminosteroidal neuromuscular blocking drugs. We hypothesized
      that the duration of action of these drugs might provide a pharmacodynamic probe
      for assessing graft function during orthotopic liver transplantation. The
      pharmacokinetics of rapacuronium and its active metabolite, ORG 9488, were
      prospectively studied in 11 patients. Rapacuronium (1.5 mg/kg) was administered
      at induction of anesthesia, 2 minutes after clamping the portal vein, and 5
      minutes after reperfusion of the new graft. Blood samples were drawn at
      intervals, and an independent laboratory analyzed plasma for both rapacuronium
      and ORG 9488. Rapacuronium's pharmacokinetics were characterized for 3 stages of
      the transplant using NONMEM software to construct mixed-effects compartmental
      models. Rapacuronium plasma clearance during the first stage of orthotopic liver
      transplantation was 7.25 mL/kg/min. Clearance decreased by only 44% during the
      anhepatic stage, to 3.91 mL/kg/min, and remained decreased after reperfusion.
      This effect suggests that an alternate clearance pathway exists. The clearance
      for ORG 9488 was 13.5 mL/kg/min during the paleohepatic and anhepatic stages, but
      it decreased 83% on reperfusion, suggesting accumulation after reperfusion. This
      pharmacokinetic analysis suggests that rapacuronium may not be suitable for use
      as a pharmacodynamic probe.

PMID- 16278699
TI  - Soft tissue sarcomas of the extremities.

PMID- 16278698
TI  - Surgical management of esophageal carcinoma.

PMID- 16278700
TI  - Patient selection and technical considerations for off-pump coronary surgery.

PMID- 16278701
TI  - Managing exsanguination: what we know about damage control/bailout is not enough.

PMID- 16278702
TI  - Baylor Regional Transplant Institute: an update on liver, kidney, and pancreas
      transplantation.

PMID- 16278703
TI  - Albert Julio Alvarez, FAHP: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 16278704
TI  - Harold Clifton Urschel, Jr., MD, LLD(HON), DS(HON): a conversation with the
      editor. Interview by William Clifford Roberts.

PMID- 16278705
TI  - Clinical outcomes in patients with type 2 diabetes managed by a diabetes resource
      nurse in a primary care practice.
AB  - OBJECTIVES: The purpose of this observational cohort study was to observe
      outcomes in geriatric (aged > or =65 years) and nongeriatric (<65 years) patients
      after employing a diabetes resource nurse (DRN) case manager in a suburban 12
      physician family practice. STUDY DESIGN: Data were collected by retrospective
      chart review of 106 patients enrolled in the diabetes care project who completed
      at least 6 months of the project between March 1999 and January 2001. POPULATION:
      Patients were recruited by either referral from their primary physician or
      invitation from the DRN. OUTCOMES MEASURED: Utilizing measures from the American
      Diabetes Association and the Diabetes Quality Improvement Project, comprehensive
      protocols were developed for implementation of process measures and management of
      glucose by the DRN. Active management protocols were not put in place for
      hypertension, lipids, or depression, but appropriate clinical measures were taken
      during patient visits. Data were collected at baseline, 6 months, and 12 months.
      RESULTS: Improvements in process measures were seen for geriatric and
      nongeriatric patients: 77% of patients had foot exams, 100% had > or =2 blood
      pressure measurements, 92% had eye exams, and 99% had lipid profiles. Both groups
      had improvement in hemoglobin A1c levels (means 7.2% to 6.6% for geriatric
      patients and 8.9% to 6.8% for nongeriatric patients). The number of hypoglycemia
      incidents decreased in both groups. Depression scores improved in the
      nongeriatric group. CONCLUSIONS: Results appear to corroborate a growing body of
      evidence supporting nurse intervention protocols as a way to improve diabetes
      care. A randomized controlled trial is planned to examine the effectiveness of
      the DRN.

PMID- 16278706
TI  - Collaborative colorectal cancer screening: a successful quality improvement
      initiative.
AB  - PROBLEM: Low screening and referral rates for colorectal cancer at a primary care
      clinic suggest the need for alternative methods to identify patients and complete
      the screening process. DESIGN: A review of >5000 medical charts established
      baseline screening and referral data. After a 3-month trial of a screening
      protocol, the research team conducted a follow-up medical chart review to
      determine referral levels. BACKGROUND AND SETTING: The clinic is an 8-physician
      primary care facility in Southlake, Texas, and is one of 36 clinics affiliated
      with HealthTexas Provider Network. KEY MEASURES FOR IMPROVEMENT: The goal was to
      increase referrals for colorectal cancer to at least 85% among patients aged 50
      to 75 years. STRATEGIES FOR IMPROVEMENT: The entire staff of the primary care
      clinic and the gastroenterology office became involved in the referral process.
      The team used simple tools such as chart stickers to draw attention to patients
      requiring screening, generation of referral forms that were numbered for follow
      up and faxed to the gastroenterologists, and patient educational material on
      colorectal cancer screening. These tools were designed to overcome specific
      barriers to successful screening that the team had identified. EFFECTS OF CHANGE:
      Referrals for sigmoidoscopy, colonoscopy, and double-contrast barium enema
      increased from 47% to 86%. Fecal occult blood testing was arranged for additional
      patients through the primary care office. Revenues related to colonoscopies
      increased by about 50% for the gastroenterologist group, the hospital, and the
      pathology group affiliated with Southlake Family Medicine. LESSONS LEARNED: This
      colorectal cancer screening protocol succeeded in its 3-month trial because it
      was collaborative, opportunistic, simple, and made good business sense. The
      protocol is now being implemented at other HealthTexas Provider Network offices.

PMID- 16278707
TI  - Invited commentary: Preventing colon cancer: looking over the horizon.

PMID- 16278708
TI  - Improving colorectal cancer screening through clinical systems redesign.

PMID- 16278709
TI  - Severe headache for 5 weeks.

PMID- 16278711
TI  - Group beating resulting from ventricular parasystole.

PMID- 16278710
TI  - Diverse manifestations associated with a single dermatosis.

PMID- 16278712
TI  - Ezetimibe (Zetia): a new type of lipid-lowering agent.

PMID- 16278713
TI  - The learned intermediary doctrine and its effects on prescribing physicians.

PMID- 16278714
TI  - Facts and ideas from anywhere.

PMID- 16278715
TI  - Predictors for nonsentinel node involvement in breast cancer patients with
      micrometastases in the sentinel lymph node.
AB  - Sentinel lymph node (SLN) biopsy in breast cancer allows for a more thorough
      pathologic assessment with serial sectioning and cytokeratin staining. This has
      resulted in increased detection of micrometastatic disease (tumor size < 2 mm) in
      the SLN. Unfortunately, the value of completion axillary dissection after finding
      micrometastatic disease in the SLN remains poorly defined. Over a 2-year period,
      a prospective database of 305 patients who underwent SLN biopsy for breast cancer
      at Baylor University Medical Center was reviewed. Eighty-four (27.5%) of the
      patients had evidence of metastatic disease in the SLN. Twenty-four of the 41
      patients identified as having micrometastatic disease in the SLN underwent
      completion axillary lymph node dissection. In these patients, all nonsentinel
      nodes were further studied by serial sectioning and immunohistochemistry. The
      median age of these 24 patients was 52 years (range, 34-83). Their primary tumor
      stages were T1a and T1b (n = 5), T1c (n = 15), and T2 (n = 4). A total of 328
      nonsentinel lymph nodes were examined, including 225 from patients with
      infiltrating ductal carcinoma (n = 17) and 103 from patients with infiltrating
      lobular carcinoma (n = 7). In the patients with infiltrating ductal carcinoma, no
      additional nodal metastases were identified, while in those with infiltrating
      lobular carcinoma, additional nodal disease was found in 5 lymph nodes (2 of 12
      patients, 17%). Primary tumor characteristics were not predictive of additional
      nodal disease. These data suggest that patients with micro-metastasis in the SLN
      from infiltrating lobular carcinoma have a significant risk of harboring
      additional nodal disease and should undergo completion axillary dissection.
      However, those with micrometastatic disease from infiltrating ductal carcinoma
      have a very low incidence of additional metastasis and may not need completion
      axillary dissection.

PMID- 16278716
TI  - Evaluation and management of the incidental adrenal mass.

PMID- 16278718
TI  - Quinine allergy causing acute severe systemic illness: report of 4 patients
      manifesting multiple hematologic, renal, and hepatic abnormalities.
AB  - Quinine is widely used for the common symptom of leg cramps. Quinine tablets
      require a prescription, but quinine and the product from which it is derived,
      cinchona, are also available without prescription. They are components of over
      the-counter remedies for many common symptoms, of nutrition products, and of
      beverages such as tonic water and bitter lemon. Although quinine has been used
      for centuries, initially as an extract from the bark of the cinchona tree,
      allergic reactions to quinine can be severe and can affect multiple organs. These
      allergic reactions can cause thrombocytopenia, neutropenia, anemia, disseminated
      intravascular coagulation, acute renal failure, liver toxicity, and neurological
      abnormalities. Because quinine use is often intermittent, defining quinine as a
      cause of an acute disorder may be difficult. Moreover, since quinine use is often
      self-regulated, patients may not mention it in response to direct questions about
      medication use, adding to diagnostic difficulty. The diversity and severity of
      quinine-associated disorders and the difficulties of diagnosis are illustrated by
      the presentation of 4 case histories. Awareness of the variety of potential
      quinine-associated reactions is important for accurate diagnosis and critical for
      prevention of recurrent illness.

PMID- 16278719
TI  - Debate on the use of arthroscopic surgery for osteoarthritis of the knee.

PMID- 16278717
TI  - Oncologic positron emission tomography: a surgical perspective.

PMID- 16278721
TI  - Physical medicine and rehabilitation at Baylor University Medical Center.

PMID- 16278722
TI  - Baylor University Medical Center then and now.

PMID- 16278720
TI  - History of the Baylor Charles A. Sammons Cancer Center.

PMID- 16278724
TI  - Peter Allen Dysert II, MD: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 16278725
TI  - Zelig ("ZECK") Herbert Lieberman, MD: a conversation with the editor. Interview
      by William Clifford Roberts.

PMID- 16278723
TI  - Gary L. Davis, MD: a conversation with the editor. Interview by William Clifford
      Roberts.

PMID- 16278726
TI  - Pelvic pain and history of previous pelvic surgery.

PMID- 16278728
TI  - Mediation.

PMID- 16278727
TI  - Angiotensin II receptor blockers.

PMID- 16278729
TI  - Facts and ideas from anywhere.

PMID- 16278730
TI  - Gastroduodenal Crohn's disease.

PMID- 16278731
TI  - Considerations in nerve repair.

PMID- 16278732
TI  - Communication gaffes: a root cause of malpractice claims.

PMID- 16278736
TI  - Facts and principles learned at the 30th Annual Williamsburg Conference on Heart
      Disease.

PMID- 16278734
TI  - Dimensions of consciousness.

PMID- 16278737
TI  - Baylor Research Institute: 2003 update.

PMID- 16278738
TI  - Martin Alan Menter, MD: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 16278740
TI  - Ellen Taylor Seldin: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 16278741
TI  - Headaches and seizures.

PMID- 16278739
TI  - Donald Wayne Seldin, MD: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 16278742
TI  - Psoriasiform lesions on trunk and palms.

PMID- 16278743
TI  - A 30-year-old pregnant woman with bradycardia.

PMID- 16278744
TI  - Voriconazole: the newest triazole antifungal agent.

PMID- 16278745
TI  - Handling requests from attorneys.

PMID- 16278746
TI  - Facts and ideas from anywhere.

PMID- 16278747
TI  - Managing conflict of interest: sense and sensibility.

PMID- 16278748
TI  - The Evidence Based Medicine approach to diagnostic testing: practicalities and
      limitations.
AB  - Evidence-Based Medicine (EBM) has become a popular approach to medical decision
      making and is increasingly part of undergraduate and postgraduate medical
      education. EBM follows four steps: 1. formulate a clear clinical question from a
      patient's problem; 2. search the literature for relevant clinical articles; 3.
      evaluate (critically appraise) the evidence for its validity and usefulness; 4.
      implement useful findings into clinical practice. This review describes the
      concepts, terminology and skills taught to attendees at EBM courses, focusing
      specifically on the approach taken to diagnostic questions. It covers how to ask
      an answerable clinical question, search for evidence, construct diagnostic
      critically appraised topics (CATs), and use sensitivity, specificity, likelihood
      ratios, kappa and phi statistics. It familiarises readers with the lexicon and
      techniques of EBM and allows better understanding of the needs of EBM
      practitioners.

PMID- 16278750
TI  - Biochemical assessment and long-term monitoring in patients with acromegaly:
      statement from a joint consensus conference of the Growth Hormone Research
      Society and the Pituitary Society.

PMID- 16278749
TI  - Insulin and insulin resistance.
AB  - As obesity and diabetes reach epidemic proportions in the developed world, the
      role of insulin resistance and its consequences are gaining prominence.
      Understanding the role of insulin in wide-ranging physiological processes and the
      influences on its synthesis and secretion, alongside its actions from the
      molecular to the whole body level, has significant implications for much chronic
      disease seen in Westernised populations today. This review provides an overview
      of insulin, its history, structure, synthesis, secretion, actions and
      interactions followed by a discussion of insulin resistance and its associated
      clinical manifestations. Specific areas of focus include the actions of insulin
      and manifestations of insulin resistance in specific organs and tissues,
      physiological, environmental and pharmacological influences on insulin action and
      insulin resistance as well as clinical syndromes associated with insulin
      resistance. Clinical and functional measures of insulin resistance are also
      covered. Despite our incomplete understanding of the complex biological
      mechanisms of insulin action and insulin resistance, we need to consider the
      dramatic social changes of the past century with respect to physical activity,
      diet, work, socialisation and sleep patterns. Rapid globalization, urbanisation
      and industrialization have spawned epidemics of obesity, diabetes and their
      attendant co-morbidities, as physical inactivity and dietary imbalance unmask
      latent predisposing genetic traits.

PMID- 16278751
TI  - Diagnostic molecular pathology: current techniques and clinical applications,
      part I.

PMID- 16278752
TI  - A randomized trial of valved vs nonvalved implantable ports for vascular access.
AB  - BACKGROUND: Vascular access devices placed into the central venous system are
      used routinely in the medical management of many patients. Catheter tip occlusion
      is a common complication of open-ended catheters, causing difficulty with blood
      withdrawal and infusion. This study evaluated whether a valved subcutaneous port
      system would have fewer associated complications than a standard nonvalved port.
      METHODS: Study subjects requiring port placement were randomized to receive a
      PASV (valved) port or a nonvalved BardPort. Standard technique was used to place
      both types of ports. Patients were monitored for 180 days after implantation, and
      data on major complications were collected. Difficulty with blood return and
      excess time spent accessing the port were studied as indicators of catheter tip
      occlusion. This study is an interim analysis of an ongoing prospective study,
      with an anticipated accrual of 100 patients. RESULTS: Fifty-four patients were
      randomized to receive either the PASV port (n = 27) or a BardPort (n = 27). All
      patients required venous access for treatment of malignancy. No major
      complications were identified from port placement. No patient had major sepsis
      due to infected catheters. Overall complications included catheter leakage in 1
      patient (3.7%, BardPort) and venous thrombosis in 1 patient in each group (3.7%
      per group). Difficulty in blood draw was noted in the PASV group on 16 of 273
      (5.9%) port accessions and in the BardPort group on 30 of 266 (11.3%) accessions
      (P = 0.04). Thrombolytic agents were required in 14 (5.1%) port accessions in the
      PASV group and 21 (7.9%) port accessions in the BardPort group (P = 0.25).
      Significantly more total time was spent ensuring adequate blood draw from
      BardPorts as opposed to PASV ports (870 vs 435 minutes, respectively) (P = 0.01).
      CONCLUSION: This initial analysis reveals that the valved PASV port system is
      associated with significantly fewer instances of poor blood return and thus
      decreases the time required for nurses to obtain blood return before infusion.

PMID- 16278753
TI  - Dispelling the myths of exercise and asthma.

PMID- 16278754
TI  - Outcomes of endoluminal gastric plication for the treatment of gastroesophageal
      reflux disease.

PMID- 16278755
TI  - Summaries from the meeting "International Update on Osteoarthritis of the Knee".

PMID- 16278757
TI  - Current challenges and choices in scientific publication.

PMID- 16278756
TI  - Angiographic confirmation of graft patency after coronary artery bypass graft
      surgery using interrupted nitinol clips.

PMID- 16278758
TI  - History of cardiology at Baylor University Medical Center.

PMID- 16278759
TI  - History of the cardiothoracic surgical service at Baylor University Medical
      Center.

PMID- 16278760
TI  - A brief history of urology at Baylor University Medical Center.

PMID- 16278762
TI  - John Flake Anderson, MD: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 16278761
TI  - History of ophthalmology at Baylor University Medical Center.

PMID- 16278763
TI  - John W. Hyland, MD: a conversation with the editor. Interview by William Clifford
      Roberts.

PMID- 16278764
TI  - Thomas John (Jock) Murray, OC, MD, FRCP(C), MACP, LLD(HON), DSc(Hon), FRCP(Lon):
      a conversation with the editor. Interview by William Clifford Roberts.

PMID- 16278765
TI  - Persistent rash on the face and lips.

PMID- 16278766
TI  - Incidental skeletal abnormalities in a 22-year-old man.

PMID- 16278767
TI  - Exercise electrocardiogram.

PMID- 16278768
TI  - Chest pain in an adolescent.

PMID- 16278769
TI  - Ziprasidone mesylate (Geodon for injection): the first injectable atypical
      antipsychotic medication.

PMID- 16278770
TI  - Package inserts and the standard of care.

PMID- 16278771
TI  - Facts and ideas from anywhere.

PMID- 16278772
TI  - Standardised, metabolite-specific assays with validated decision limits: utopian
      ideal or achievable goal?

PMID- 16278773
TI  - HbA1c standardisation destination--global IFCC Standardisation. How, why, where
      and when--a tortuous pathway from kit manufacturers, via inter-laboratory
      lyophilized and whole blood comparisons to designated national comparison
      schemes.
AB  - Glycohaemoglobins were first used in routine clinical laboratories for diabetes
      monitoring around 1977 and at the time all methods had either no calibrators, or
      used material with assayed values derived from individual manufacturers' assays.
      Over the next five to fifteen years, lyophilised and whole blood sample exchanges
      were shown to improve inter-laboratory variability markedly. The use of a precise
      HPLC method as the "standard method" in the Diabetes Control and Complications
      Trial (DCCT) led to significant further improvement. National standardisation
      schemes in the mid to late 1990s in the USA, Japan and Sweden further improved
      the quality and accuracy of HbA1c assays in clinical use. The work of the IFCC
      Working Group on Standardisation of HbA1c in establishing true International
      Reference Methods for HbA1c and the successful preparation of pure HbA1c
      calibration material should lead to further improvements in inter-method and
      inter-laboratory variability, essential to the long-term monitoring of patients
      with diabetes.

PMID- 16278774
TI  - Vitamin D: a hormone for all seasons--how much is enough?
AB  - Further understanding of its endocrine mechanisms and increased evidence for
      autocrine/paracrine actions has recently enhanced our knowledge of the biological
      activities of the vitamin D metabolite 1,25-dihydroxyvitamin D (1,25(OH)2D). The
      recognition of the contribution of vitamin D depletion to increased risk of
      osteoporosis, and most importantly the risk of hip fracture in the elderly, has
      increased the clinical significance of clinical laboratory testing for vitamin D
      status. Research has revealed that at least three genes contribute to vitamin D
      activity within tissues. These are the vitamin D receptor as well as two major
      vitamin D metabolising enzymes, CYP27B1, responsible for synthesis of 1,25(OH)2D
      and CYP24, responsible for catabolism of vitamin D metabolites. Current research
      focuses on the contribution of vitamin D metabolism to increasing vitamin D
      activity. This is of particular interest in bone forming cells where increased
      1,25(OH)2D activity has been proposed to contribute to strengthening the
      skeleton. As well, solid tumours such as prostate, breast and colon cancers are
      another increasing area of vitamin D research. The major issues for the clinical
      laboratory in vitamin D testing include defining clinical decision limits for the
      interpretation of serum 25-hydroxyvitamin D (25OHD) levels and improving the
      precision and accuracy of this assay.

PMID- 16278775
TI  - Improving the measurement of 25-hydroxyvitamin D.

PMID- 16278776
TI  - Androgen insufficiency in ageing men: how is it defined and should it be treated?

PMID- 16278777
TI  - Are routine testosterone assays good enough?

PMID- 16278778
TI  - [LVII Annual Meeting of the Spanish Society of Neurology, Barcelona, Spain, 23-25
      November 2005. Abstracts].

PMID- 16278779
TI  - Ether stress increases adrenomedullin gene expression and levels in the rat
      adrenal.
AB  - To study the contribution of adrenomedullin in the adrenal medulla in the stress
      response, we measured plasma and adrenal levels of adrenomedullin in sham
      operated (intact) rats and in rats without adrenal medulla, with or without
      exposure to ether vapor for 15 min. Adrenomedullin levels decreased drastically
      after demedullation. Effect stress resulted in increased adrenomedullin levels in
      both adrenal and plasma in sham-operated rats, but not in demedullated rats. The
      responses of plasma adrenocorticotropin to stress were similar, but the
      elevations in plasma corticosterone levels were significantly less in
      demedullated rats. In the sham-operated rat, preproadrenomedullin mRNA levels
      were increased after stress, and this effect was not blocked by pretreatment with
      hexamethonium. We conclude that stress increases adrenomedullin synthesis and
      secretion from the adrenal medulla through a hexamethonium-insensitive mechanism,
      and that adrenomedullin release from the adrenal medulla may play a role in
      cortical steroidogenesis.

PMID- 16278780
TI  - Statins modulate the levels of osteoprotegerin/receptor activator of NFkappaB
      ligand mRNA in mouse bone-cell cultures.
AB  - Statins stimulate bone formation partly by inducing osteoblast differentiation,
      although there is controversy about the effects of statins on bone mineral
      density and fracture risk. Several studies have revealed that statins suppress
      bone resorption. However, the mechanism by which statins inhibit bone resorption
      is still unclear. The present study was performed to clarify the effects of
      statins on osteoclast formation as well as the levels of osteoprotegerin (OPG)
      and receptor activator of NFkappaB ligand (RANKL) mRNA in mouse bone-cell
      cultures by semiquantitative RT-PCR. 10(-8) M 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3] significantly stimulated osteoclast formation and 10(-6) M statins
      (mevastatin and simvastatin) significantly antagonized osteoclast formation
      stimulated by 1,25(OH)2D3 in mouse bone-cell cultures, including both osteoblasts
      and osteoclasts. 10(-6) M mevastatin and simvastatin increased the level of OPG
      mRNA in mouse bone-cell cultures. On the other hand, 10(-6) M mevastatin and
      simvastatin inhibited the level of RANKL mRNA in these cultures. In conclusion,
      the present study demonstrates that statins inhibit osteoclast formation in mouse
      bone-cell cultures. Moreover, statins also increased and decreased the levels of
      OPG and RANKL mRNA expression in these cultures, respectively. The modulation of
      OPG/RANKL may be involved in the inhibition of osteoclast formation by statins.

PMID- 16278781
TI  - Bone microenvironment-related growth factors, zoledronic acid and dexamethasone
      differentially modulate PTHrP expression in PC-3 prostate cancer cells.
AB  - Bone metastasis microenvironment-related growth factors such as insulin-like
      growth factor 1 (IGF-1), transforming growth factor beta 1 (TGF-beta1), basic
      fibroblast growth factor (bFGF) and interleukin 6 (IL-6) show survival factor
      activity, thereby inhibiting chemotherapy-induced apoptosis of PC-3 prostate
      cancer cells in vitro. Recently, zoledronic acid has been shown to induce
      apoptosis in PC-3 prostate cancer cells while overexpression of parathyroid
      hormone-related protein (PTHrP) inhibits serum deprivation-induced apoptosis in
      PC-3 cells. Consequently, we have investigated whether IGF-1, TGF-beta1, bFGF, IL
      6, zoledronic acid and/or dexamethasone affect the expression of the PTHrP and
      type I PTH/PTHrP receptor (PTH.1R) in PC-3 prostate cancer cells using relative
      quantitative PCR and real-time PCR (expression at mRNA level) and
      immunocytochemical and immunofluorescence analysis (expression at protein level).
      Our data show that IGF-1, TGF-beta1, bFGF and IL-6 increase PTHrP mRNA expression
      and its perinuclear localization, while zoledronic acid (50 muM, 100 muM for 24 h
      and 48 h) and dexamethasone suppress PTHrP expression in PC-3 cells. We did not
      detect any appreciable change of the PTH.1R expression due to IGF-1, TGF- beta1,
      bFGF, IL-6, zoledronic acid or dexamethasone in PC-3 cells. Therefore, it is
      conceivable that bone metastasis microenvironment-related survival factor/anti
      apoptotic activity and zoledronic acid anticancer action/pro-apoptotic activity
      on PC-3 cells is mediated, at least in part, by differential modulation of PTHrP
      expression.

PMID- 16278782
TI  - The effect of the HIV protease inhibitor ritonavir on proliferation,
      differentiation, lipogenesis, gene expression and apoptosis of human
      preadipocytes and adipocytes.
AB  - HIV patients in highly active antiretroviral therapy (HAART) develop
      lipodystrophy and insulin resistance. Protease inhibitors have been shown to
      alter adipocyte metabolism in murine cell lines. In this study, biological
      effects of the HIV protease inhibitor, ritonavir, were investigated on human SGBS
      preadipocytes and adipocytes. Ritonavir dose-dependently impaired preadipocyte
      proliferation and adipogenic differentiation. Gene expression analysis measured
      by real-time PCR, showed no effect of ritonavir (up to 20 microM) on expression
      of mRNA of PPARgamma2 and SREBP1c, but suppressed adiponectin mRNA while
      increasing IL-6 mRNA expression. In human adipocytes, ritonavir at therapeutic
      concentrations inhibited insulin-stimulated lipogenesis, reduced GLUT4 mRNA,
      fatty acid synthase and adiponectin expression, while increasing IL-6 mRNA
      expression. Finally, long-term treatment (72 and 120 h) of SGBS adipocytes but
      not preadipocytes with ritonavir induced apoptosis in up to 15% of the cells. All
      together, these data show effects of ritonavir on human preadipocytes and
      adipocytes aiming at reducing adipose tissue mass and increasing insulin
      resistance. These in vitro findings may partly explain the clinical findings in
      patients under HAART. Furthermore, SGBS cells may serve as a useful tool in
      further investigation of the mechanism of protease inhibitor action in human
      adipocytes.

PMID- 16278783
TI  - Increase of insulin sensitivity by stevioside in fructose-rich chow-fed rats.
AB  - The intake of dietary fructose has undergone a marked increase around the world,
      especially the developed countries, in recent times. Stevioside, a glycoside
      contained in the leaves of Stevia rebaudiana Bertoni (Compositae), was used to
      screen the effect induced by a diet containing 60% fructose on insulin resistance
      in rats. Single oral administration of stevioside for 90 min decreased plasma
      glucose concentrations in a dose-dependent manner in rats receiving fructose-rich
      chow for four weeks. In addition, insulin action on glucose disposal rate was
      measured using the glucose-insulin index, the product of the areas under the
      curve of glucose, and insulin during the intraperitoneal glucose tolerance test.
      Oral administration of stevioside (5.0 mg/kg) in rats given four weeks of
      fructose-rich chow for 90 min reversed the value of glucose-insulin index,
      indicating that stevioside has the ability to improve insulin sensitivity in this
      insulin-resistant animal model. Time for the loss of plasma glucose lowering
      response to tolbutamide (10.0 mg/kg, i. p.) in fructose-rich chow fed rats was
      also markedly delayed by repeated stevioside treatment three times daily compared
      to the vehicle-treated group. The plasma glucose-lowering activity of tolbutamide
      was introduced to account for varying levels of endogenous insulin secretion, and
      is widely used as the indicator of insulin resistance development. Thus, it
      provided the supportive data that repeated oral administration of stevioside
      delayed the development of insulin resistance in rats on a high-fructose diet.
      Increased insulin sensitivity by stevioside administration was further identified
      using the plasma glucose-lowering action of exogenous insulin in streptozotocin
      induced diabetic rats (STZ-diabetic rats). Oral administration of stevioside at
      0.2 mg/kg three times daily into STZ-diabetic rats for ten days increased the
      response to exogenous insulin. Taken together, this demonstrated that oral
      administration of stevioside improves insulin sensitivity, and seems suitable as
      an adjuvant for diabetic patients and/or those that consume large amounts of
      fructose.

PMID- 16278784
TI  - Soluble TNF receptors and albuminuria in non-obese Japanese type 2 diabetic
      patients.
AB  - The aim of this study was to investigate the relationships between albuminuria
      and tumor necrosis factor (TNF)-alpha or soluble TNF receptors (sTNF-R1, sTNF-R2)
      in eighty-eight non-obese Japanese type 2 diabetic patients stratified into two
      groups according to albuminuria status-microalbuminuria or normoalbuminuria.
      Patients with microalbuminuria were older and had significantly higher
      concentrations of sTNF-R1 and sTNF-R2 than those with normoalbuminuria. There
      was, however, no significant difference in sex, diabetes duration, smoking, BMI,
      systolic and diastolic blood pressure, HbA (1c), serum creatinine, and lipid
      profile between the two groups. Although serum TNF-alpha was positively
      correlated to serum sTNF-R1 and sTNF-R2, serum TNF-alpha level did not differ
      with respect to albuminuria. Univariate regression analysis showed that urinary
      albumin concentration was positively correlated to age (r=0.380, p<0.001), serum
      creatinine (r=0.214, p<0.05) and concentrations of sTNF-R1 (r=0.364, p<0.001) and
      sTNF-R2 (r=0.342, p<0.005). Other variables, including TNF-alpha, were not
      associated with albuminuria. Multiple regression analyses showed that urinary
      albumin concentration was independently predicted by the level of sTNF-R1
      (F=32.1), which explained 26.3% of the variability of urinary albumin
      concentration. From these results, it can be concluded that serum soluble TNF
      receptor is an important independent factor associated with albuminuria in non
      obese Japanese type 2 diabetic patients.

PMID- 16278785
TI  - New "pre-diabetes" category and the metabolic syndrome in Japanese.
AB  - BACKGROUND: Recently, impaired fasting glucose (IFG) was redefined as fasting
      plasma glucose of 100-125 mg/dl, and individuals with IFG and/or impaired glucose
      tolerance (IGT) were referred to as having "pre-diabetes". However, there is a
      lack of data using the new definition of IFG and "pre-diabetes". OBJECTIVE: The
      aim of this study was to examine associations of the metabolic syndrome
      components with the new "pre-diabetes" category in relatively lean Japanese.
      METHODS: Six hundred and sixty-one Japanese study participants underwent a 75 g
      oral glucose tolerance test. They were classified into three groups-normal
      (n=225), pre-diabetes (n=308), and diabetes (n=128). The metabolic syndrome was
      defined according to the National Cholesterol Education Program Adult Treatment
      Panel III, as modified for waist circumference criteria by the Regional Office
      for the Western Pacific Region of WHO. RESULTS: Prevalence of the metabolic
      syndrome in each group was 10.7%, 27.9%, and 53.9%, respectively. Of the
      metabolic syndrome components, the OR for prevalent pre-diabetes was 2.00 (95%
      CI, 1.73-2.31, p<0.001) for fasting glucose, 1.93 (95% CI, 1.54-2.42, p<0.001)
      for waist circumference, and 1.36 (95% CI, 1.10-1.68, p=0.005) for triglycerides.
      Similar associations were found in prevalent diabetes. Insulin resistance
      assessed using Stumvoll's index was significantly associated with both pre
      diabetes and diabetes. CONCLUSION: Pre-diabetes and the metabolic syndrome
      frequently coexist in relatively lean Japanese. This association seems to link
      with abdominal adiposity and insulin resistance.

PMID- 16278786
TI  - Day-long subcutaneous infusion of exenatide lowers glycemia in patients with type
      2 diabetes.
AB  - Exenatide (exendin-4) is an incretin mimetic with potential antidiabetic
      activity. This study examined the effects of a continuous subcutaneous (SC)
      infusion of exenatide (0.2, 0.4, 0.6, or 0.8 microg/kg/day) or placebo (PBO) on
      glycemic control over 23 h intervals. Twelve subjects with type 2 diabetes
      treated with metformin and/or diet received 10 infusions (4 exenatide, 6 PBO) on
      consecutive days. Exenatide was given in a dose-increasing design with at least
      one placebo infusion between each exenatide infusion, and with meals and a snack
      provided during the first 14 h of infusion. Plasma exenatide concentrations were
      dose-proportional. Plasma glucose (4-23 h) was lower in all exenatide arms
      compared to placebo (p<0.0001). The change in insulin/glucagon ratio and amylin
      concentrations from pre-infusion to post-infusion was increased (p<0.005, p<0.05,
      respectively) in the combined exenatide arms, but remained unchanged in the
      placebo groups. Nausea and vomiting were the most common treatment emergent
      adverse events. Exenatide infusion also appeared to have positive effects on beta
      cell and alpha-cell function as measured by proinsulin/insulin ratios and mean
      glucagon concentrations. In summary, exenatide lowered plasma glucose during both
      prandial and fasting states when delivered as a continuous SC infusion over
      twenty-three hours, suggesting that exenatide can provide day-long glycemic
      control in patients with type 2 diabetes.

PMID- 16278787
TI  - Thyroid hormone dysregulation in intrauterine growth retardation associated with
      maternal malnutrition and/or anemia.
AB  - Data on the effect of maternal malnutrition and/or anemia on thyroid hormone
      regulation in human fetuses are scarce, and would be of great importance in
      examining the relevance of Barker's hypothesis, which proposes adaptation of
      fetuses to undernutrition leading to permanent metabolic and endocrine changes
      that form the basis of adult diseases. To examine the quantitative variations in
      thyroid hormone profile of neonates born to malnourished and/or anemic mothers,
      we quantitated the T3, T4, rT3 and TSH levels in cord blood of neonates and
      maternal blood of their corresponding mothers that are malnourished and/or
      anemic. Further, we classified neonates born to each of these groups of mothers
      into Small for Gestational Age (SGA) or Appropriate for Gestational Age (AGA)
      based on the intrauterine growth curve for our population, and examined the
      thyroid hormone profile in these neonates. Our results show that firstly, the
      effects of malnutrition or anemia on thyroid hormone profile are distinct,
      secondly, significantly higher levels of cord blood T4 and correspondingly lower
      levels of T3 and rT3 are observed in the neonates born to anemic and malnourished
      mothers and thirdly, decreases in cord blood T3 levels were observed in Small for
      Gestational Age neonates born to anemic mothers. These observations lead us to
      speculate that alterations in the pituitary-thyroid function result in beneficial
      adaptations to the hostile intrauterine environment in malnutrition related
      growth retardation and anemia.

PMID- 16278788
TI  - Effects of long-term beer ingestion on plasma concentrations and urinary
      excretion of purine bases.
AB  - To investigate the long-term effects of beer ingestion on plasma concentrations
      of purine bases (hypoxanthine, xanthine, and uric acid), ten healthy males
      ingested beer (15 ml/kg body weight) every evening for three months. Blood and 24
      hour urine samples were collected in the morning on one day before and one, two,
      and three months after starting the experiment to determine the plasma
      concentrations and urinary excretion of uric acid, hypoxanthine, and xanthine.
      Plasma concentrations and urinary excretion of uric acid, hypoxanthine, and
      xanthine in five of the participants that did not regularly ingest beer at a
      quantity of more than 15 ml/kg body weight in a single day prior to the
      experiment were not increased during the experimental period. In contrast, plasma
      concentrations and urinary excretion of uric acid were increased in five
      participants who regularly ingested more than 15 ml/kg body weight of beer in a
      single day prior to the experiment, although hypoxanthine and xanthine levels
      were not significantly increased during the experimental period. In both groups,
      uric acid clearance and purine ingestion were not significantly different
      throughout the study. Our results suggest that the production of uric acid caused
      by ethanol ingestion from beer is a significant contributor to the increase in
      plasma uric acid concentration in patients that regularly consume more than 15
      ml/kg body weight of beer each day. Therefore, patients with gout should be
      encouraged to refrain from drinking large amounts of beer on a daily basis.

PMID- 16278789
TI  - Increased plasma ghrelin levels in chronic renal failure are not associated with
      hemodynamic parameters.
AB  - BACKGROUND/AIMS: Hardly anything is known about the effect of renal function on
      plasma ghrelin levels. Ghrelin is an orexigenic hormone with important
      hemodynamic effects. We examined differences in plasma ghrelin levels between
      chronic renal failure (CRF) patients and healthy subjects, and ghrelin's
      relationship with indices of left ventricular (LV) function. METHODS: Fasting
      total plasma ghrelin levels were measured in 122 CRF patients (57 on, 65 not on
      hemodialysis) and 57 control subjects. Indices of LV function were evaluated
      using echocardiography. RESULTS: Total plasma ghrelin levels were higher in
      patients with CRF compared to controls, but were not different between patients
      on and those not on hemodialysis. In a multivariate linear regression model,
      presence of kidney dysfunction explained 41 % of the variability of ghrelin
      values. The etiology of renal failure (diabetic nephropathy or not) had no
      influence on ghrelin levels in the renal patients. Ghrelin levels were not
      associated with indices of LV systolic function or blood pressure in these
      patients. CONCLUSION: Fasting plasma ghrelin concentrations are higher in CRF
      patients regardless of their need for hemodialysis compared to controls. The
      etiology of renal failure does not have any effect on plasma ghrelin levels. In
      addition, ghrelin levels are not associated with hemodynamic parameters in
      patients with CRF.

PMID- 16278790
TI  - Ghrelin expression in neuroendocrine tumours of the gastrointestinal tract with
      multiple endocrine neoplasia type 1.
AB  - Ghrelin is a novel gastrointestinal-brain hormone that was first described by
      Kojima et al. as a growth-hormone-releasing peptide. It can be isolated and
      purified from different tissues. Evidence of antiproliferative effects in
      neoplastic cells (binding to normal and neoplastic tissues) supports the
      hypothesis that ghrelin also plays an important role in endocrine regulation.
      Whether ghrelin may be involved in formation of neuroendocrine tumours (NET) of
      the gastrointestinal tract (GIT) in cases of MEN-1 is under discussion. Over the
      last sixteen years, 227 patients with GIT NET were treated at our institution.
      Mutations of the menin gene were identified in twelve patients. Eleven of these
      tumours (islet cell tumours) were localized in the pancreas and one in the
      stomach. Tissues from these tumours were resected, fixed in formalin and embedded
      in paraffin. Sections were examined by immunohistochemistry with a primary
      antibody for ghrelin. Three out of twelve NET in MEN-1 patients (25%) showed
      ghrelin expression by immunohistochemistry. Comparison between ghrelin-positive
      and ghrelin-negative tumours regarding biological activity, morphological aspects
      and clinicopathological parameters shows no substantial differences. The reported
      incidence of ghrelin expression in NET of the gastrointestinal tract by MEN-1 was
      not seen in our patients. Whether or not ghrelin has an influence on
      neuroendocrine tumour development related to deficient menin-genes is unknown.

PMID- 16278791
TI  - Interleukin-6 and mood disorders in endocrine disease.

PMID- 16278793
TI  - Evidence-based practice for cognitive-communication disorders after traumatic
      brain injury.

PMID- 16278794
TI  - The use of standardized tests for individuals with cognitive-communication
      disorders.
AB  - The assessment of individuals with cognitive-communication disorders after
      traumatic brain injury can present a major challenge to speech-language
      pathologists. For this reason, the Academy of Neurologic Communication Disorders
      and Sciences Practice Guidelines Group dedicated a specific writing committee to
      this topic. This article summarizes the writing committee's efforts related to
      the use of standardized, norm-referenced tests. The article begins with the key
      questions speech-language pathologists might ask in choosing a standardized test.
      We then provide a summary of the results of the writing committee's data
      gathering activities and a brief description of the tests that appeared to meet
      most established criteria for validity and reliability for use with this clinical
      population. The article concludes with the identification of areas in which
      instruments and additional normative data are needed.

PMID- 16278795
TI  - Nonstandardized assessment approaches for individuals with traumatic brain
      injuries.
AB  - Nonstandardized assessment procedures serve a variety of purposes, including
      determining competencies in domains for which there are no standardized tests,
      describing performance in the context of real-world settings and activities, and
      exploring the effects of systematic changes in communication and cognitive
      demands and partner supports. This article reviews evidence on the use of
      nonstandardized procedures for the assessment of individuals with traumatic brain
      injury and offers recommendations for the use of the procedures that are
      supported by the available evidence.

PMID- 16278796
TI  - Self-regulation after traumatic brain injury: a framework for intervention of
      memory and problem solving.
AB  - Self-regulation of behavior is mediated by the frontal lobes and commonly
      disrupted after a traumatic brain injury. The rehabilitation field is only now
      beginning to understand self-regulation as a set of dynamic relationships between
      metacognitive beliefs and knowledge, ongoing self-monitoring or self-assessment
      during activities, and self-control (i.e., strategy decisions). This article
      provides a framework for understanding self-regulated learning and problem
      solving, along with a summary of the existing intervention literature. We
      conclude by providing clinicians with principles that emphasize accurate self
      monitoring and explicit instruction to connect self-monitoring to strategy
      decisions.

PMID- 16278797
TI  - Behavioral and social interventions for individuals with traumatic brain injury:
      a summary of the research with clinical implications.
AB  - Specialists in communication disorders who work with individuals who have
      traumatic brain injury (TBI) often focus their rehabilitative efforts on the
      cognitive, social, and behavioral dimensions of disability. These domains of
      functioning are included in the scope of practice of the American Speech-Language
      and Hearing Association because of their close associations with communication
      effectiveness. This article summarizes relevant research findings and clinical
      perspectives in the areas of intervention for disorders of behavioral self
      regulation and social-interactive competence after TBI. This clinical summary is
      associated with a systematic evidence review sponsored by the TBI Practice
      Guidelines Group of the Academy of Neurologic Communication Disorders and
      Sciences (ANCDS).

PMID- 16278798
TI  - Instructional techniques in cognitive rehabilitation: a preliminary report.
AB  - Instruction is an essential component of effective cognitive rehabilitation,
      which requires teaching or reteaching a variety of skills and concepts to people
      with compromised learning. Currently, the field lacks a cohesive set of
      principles to guide clinicians' instructional behaviors. A review of the
      literature in related fields, in conjunction with findings in neuropsychology,
      reveals evidence-based principles that lead to effective instructional design and
      implementation. This article summarizes this work and attempts to provide
      clinicians with principles to guide their treatment planning when training or
      teaching clients with cognitive-communication disorders.

PMID- 16278799
TI  - [The H-index].

PMID- 16278800
TI  - [The concept of allostasis and allostatic load: psychoneuroimmunological
      findings].
AB  - Classical theories have conceptualized stress as a reaction to threat to the
      homeostasis within the organism requiring an adaptive response. However,
      postulating mechanisms that could link such responses to long-term detrimental
      health outcomes remains difficult. The allostatic load concept enables us to
      think about how mediators can be protective in the short run but may have
      damaging effects when overused and/or not shut off. It further facilitates the
      formulation of cause-effects cascades to explain the link of dysregulations in
      stress mediators such as glucocorticoids and catecholamines and increased
      susceptibility for certain diseases. In the first section, we briefly summarize
      the theoretical background. We then employ the concept to integrate findings from
      basic and clinical research on dysregulations of the stress response systems in
      multiple sclerosis and breast cancer. Based on this model, it seems likely that
      such dysregulations are implicated in progression and possibly pathogenesis of
      these diseases. When using allostatic load as a heuristic model, one needs to
      consider that stress mediators and outcomes are interconnected in a non-linear
      network.

PMID- 16278801
TI  - [Faustlos -- promotion of social-emotional competences in elementary schools and
      kindergartens].
AB  - Aggressive and violent behavior of children often is caused by a lack of social
      and emotional competences, which blocks constructive problem- and conflict
      management. Therefore lots of different US-American prevention approaches for the
      promotion of crucial social competences have been developed. Faustlos is the
      first German violence prevention curriculum, which promotes the social and
      emotional competences of first grade pupils and kindergarten aged children. The
      curriculum builds on the promotion of empathy, impulse control and anger
      management. Evaluation studies on the effectiveness of Faustlos prove its
      positive effects on aggressive behavior and on the promotion of social-emotional
      competence. Further, the feedback of people working with Faustlos concerning the
      acceptance and practicability of the program is positive too. Besides the
      development of additive materials (e. g. Faustlos for parents) evaluation studies
      on the long-term effects of the program are needed.

PMID- 16278803
TI  - [Assessing work motivation in rehabilitation -- presentation of new concepts and
      results related to the factorial validity].
AB  - Within the science of rehabilitation and the medical research field there is a
      lack of an adequate instrument to assess work motivation. In order to be able to
      evaluate work-referred motivation structures with their strengths and weaknesses
      a multi-dimensional viewpoint was conceptualised on the basis of an interview
      study. Three new concepts were developed to which 12 scales with 202 items were
      assigned ("motivational self image" with six scales; "motivational intention of
      action" and "motivational goodness of fit" both with three scales). In a pilot
      study using a sample of vocational rehabilitants the major part of the concepts
      was identified using factor analysis. In certain areas modifications were made,
      so that 10 scales remained forming the basis for the development of a diagnostic
      instrument.

PMID- 16278804
TI  - [The CL-BaDo -- a documentation form for consultation-liaison services].

PMID- 16278802
TI  - [work motivation -- assessment instruments and their relevance for medical care].
AB  - The relevance of work motivation for medical research and healthcare, in
      particular rehabilitation, is described. Four diagnostic instruments in the
      German language are introduced which can assess work motivation using a scale
      system: AVEM, JDS, LMI and FBTM. Their possible application and potential usage
      for the clinical area are discussed. Apart from the FBTM, none of these
      instruments can be directly used as a general instrument in a normal medical
      clinical setting. Finally, a current model for work motivation (compensatory
      model of work motivation and volition) is presented that contains basis concepts,
      which are judged as important for future research questions concerning the
      development of motivation diagnostic instruments.

PMID- 16278805
TI  - OCT-1 is over-expressed in intestinal metaplasia and intestinal gastric
      carcinomas and binds to, but does not transactivate, CDX2 in gastric cells.
AB  - Intestinal metaplasia (IM) is a preneoplastic lesion of the stomach in which
      there is transdifferentiation of the gastric mucosa to an intestinal phenotype.
      The caudal-related homeobox gene CDX2 encodes an intestine-specific transcription
      factor crucial for the regulation of proliferation and differentiation of
      intestinal cells. In addition, CDX2 is involved in the induction of IM in the
      stomach. The aim of this study was to access the putative involvement of OCT-1 in
      the induction of CDX2 expression de novo in gastric mucosa leading to the onset
      of IM. OCT-1 protein expression was evaluated by immunohistochemistry in 31
      biopsies with chronic gastritis, 15 biopsies with foci of IM and adjacent gastric
      mucosa and 42 gastric carcinomas. Furthermore, we evaluated OCT-1 binding by
      electrophoretic mobility shift assay and activation of the CDX2 promoter by co
      transfecting a CDX2 promoter/reporter construct with an OCT-1 expression vector
      in two gastric carcinoma cell lines, GP220 and MKN45. Our results show that OCT-1
      is expressed in chronic gastritis, particularly when it is adjacent to IM and is
      expressed in 87% of IM foci. Furthermore, 74% of the gastric carcinomas were
      positive for OCT-1 and a strong association was observed between OCT-1 expression
      and intestinal-type carcinoma. We identified that OCT-1 binds to the CDX2
      promoter, although we could not see a transactivation effect in gastric carcinoma
      cell lines. In conclusion, we observed increased OCT-1 expression in IM and in
      intestinal gastric carcinomas and identified the capacity of OCT-1 to bind to the
      CDX2 promoter, although we could not demonstrate a direct effect of OCT-1 in the
      transactivation of CDX2.

PMID- 16278806
TI  - Expression of receptors for putative anabolic growth factors in human
      intervertebral disc: implications for repair and regeneration of the disc.
AB  - Low back pain (LBP) is a common, debilitating and economically important
      disorder. Current evidence implicates loss of intervertebral disc (IVD) matrix
      consequent upon 'degeneration' as a major cause of LBP. Degeneration of the IVD
      involves increases in degradative enzymes and decreases in the extracellular
      matrix (ECM) component in a process that is controlled by a range of cytokines
      and growth factors. Studies have suggested using anabolic growth factors to
      regenerate the normal matrix of the IVD, hence restoring disc height and
      reversing degenerative disc disease. However, for such therapies to be successful
      it is vital that the target cells (i.e. the disc cells) express the appropriate
      receptors. This immunohistochemical study has for the first time investigated the
      expression and localization of four potentially beneficial growth factor
      receptors (i.e. TGFbetaRII, BMPRII, FGFR3 and IGFRI) in non-degenerate and
      degenerate human IVDs. Receptor expression was quantified across regions of the
      normal and degenerate disc and showed that cells of the nucleus pulposus (NP) and
      inner annulus fibrosus (IAF) expressed significantly higher levels of the four
      growth factor receptors investigated. There were no significant differences
      between the four growth factor expression in non-degenerate and degenerate
      biopsies. However, expression of TGFbetaRII, FGFR3 and IGFRI, but not BMP RII,
      were observed in the ingrowing blood vessels that characterize part of the
      disease aetiology. In conclusion, this study has demonstrated the expression of
      the four growth factor receptors at similar levels in the chondrocyte-like cells
      of the NP and IAF in both non-degenerate and degenerate discs, implicating a role
      in normal disc homeostasis and suggesting that the application of these growth
      factors to the degenerate human IVD would stimulate matrix production. However,
      the expression of some of the growth factor receptors on ingrowing blood vessels
      might be problematic in a therapeutic approach.

PMID- 16278807
TI  - The cytotoxic effect of anthrax lethal toxin on human lung cells in vitro and the
      protective action of bovine antibodies to PA and LF.
AB  - The excretion of protein toxins by vegetative cells of Bacillus anthracis is
      critical to the development of the lethal consequences of anthrax, particularly
      inhalational anthrax. Whilst the lung macrophages and other phagocytic cells
      transfer the spores from the lung cavities into the lymphatic system, and provide
      an initial germination site for the proliferation of the vegetative cells, it
      appears that much of the tissue pathology at the time of the host's death could
      be due to the action of the toxins, especially lethal toxin-protective antigen
      (PA) plus lethal factor (LF). The widespread tissue oedema and hypoxia may in
      part reflect a direct attack by lethal toxin on vascular endothelial cells. Also
      the distribution of the receptor for PA on a variety of cell types including
      epithelial cells as well as endothelial cells, and the involvement of the lungs
      in the pathology raises the question of whether lung epithelial cells are also
      susceptible to lethal toxin. To investigate this possibility a series of in vitro
      cytotoxicity experiments were carried out with human lung epithelial cells and
      microvascular endothelial cells. In these experiments lethal toxin (PA 500 ng ml(
      1) plus 10-100 ng ml(-1) LF) was shown to cause a progressive loss of cell
      viability that developed slowly over at least 3 days. Affinity purified bovine
      colostrum antibodies for both PA and LF were equally effective in providing a
      100% protection for epithelial cells from this cytotoxic action of lethal toxin.
      This was achieved at a 10:1 molar ratio of the particular antibody to its
      respective target.

PMID- 16278808
TI  - A clinical flow cytometric biomarker strategy: validation of peripheral leukocyte
      phospholipidosis using Nile red.
AB  - Phospholipidosis, or intracellular accumulation of phospholipids, is caused by
      specific classes of xenobiotics. This phenomenon represents a challenge for risk
      assessment that could benefit from the use of biomarkers in the clinical
      development of new drug candidates. Flow cytometry, coupled with the lipophilic
      fluoroprobe Nile red, was correlated to histopathology, electron microscopy and
      inorganic phosphorus detection to validate the utility of this method for
      monitoring phospholipidosis in peripheral blood leukocytes. Replicate studies
      with model test compounds were conducted in which F344 rats were given 4 or 7
      doses of either maprotiline hydrochloride, imipramine hydrochloride, tilorone
      dihydrochloride, amikacin hydrate or vehicle control. Transmission electron and
      light microscopy were used to examine peripheral blood smears and tissue samples
      for the presence of cytoplasmic vacuoles. Unstained and Nile red stained lysed
      peripheral blood samples were acquired for analysis using a FACScan flow
      cytometer. Inorganic phosphorus concentration in the liver was determined from
      extracted phospholipids and compared with flow cytometry and histological data.
      It was demonstrated that flow cytometric analysis of Nile red stained lysed whole
      blood can be used to detect drug-induced phospholipid accumulation in circulating
      peripheral leukocytes. Furthermore, clinically detectable leukocyte
      phospholipidosis may be a useful surrogate for coincident or premonitory
      detection of target organ phospholipidosis.

PMID- 16278809
TI  - Preventive effect of neutropenia on carbon tetrachloride-induced hepatotoxicity
      in rats.
AB  - The preventive effect of neutropenia on carbon tetrachloride (CCl4)-induced
      hepatotoxicity was examined in rats. In rats treated once with CCl4 (1 ml kg(-1),
      i.p.), the serum levels of alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST), indices of liver cell damage, and the hepatic activity of
      myeloperoxidase (MPO), an index of tissue neutrophil infiltration, increased at 6
      h after the intoxication and further increased at 24 h. The liver of CCl4 
      treated rats showed an increase in the concentration of thiobarbituric acid
      reactive substances (TBARS), an index of lipid peroxidation, and decreases in
      superoxide dismutase (SOD) activity and reduced glutathione (GSH) concentration
      at 6 h after the intoxication followed by a further increase in TBARS
      concentration and further decreases in SOD activity and GSH concentration at 24 h
      with increased xanthine oxidase (XO) activity at 24 h. Neutropenic treatment with
      anti-rat neutrophil antiserum (2 ml kg(-1), i.p.) at 0.5 h after CCl4
      intoxication attenuated the increases in serum ALT and AST activities and hepatic
      MPO activity and TBARS concentration and the decreases in hepatic SOD activity
      and GSH concentration found at 6 and 24 h after CCl4 intoxication and the
      increase in hepatic XO activity found at 24 h after the intoxication. This
      neutropenia reduced the necrotic and degenerative changes with inflammatory cell
      infiltration in the liver cell of CCl4 -treated rats. These results indicate that
      neutropenia prevents CCl4 -induced hepatotoxicity in rats by attenuating the
      disruption of hepatic reactive oxygen species metabolism mediated by neutrophils
      accumulating in the liver tissue.

PMID- 16278810
TI  - Tissue-specific mtDNA lesions and radical-associated mitochondrial dysfunction in
      human hearts exposed to doxorubicin.
AB  - Doxorubicin causes a chronic cardiomyopathy. Although the exact pathogenesis is
      unknown, recent animal data suggest that somatically acquired alterations of
      mitochondrial DNA (mtDNA) and concomitant mitochondrial dysfunction play an
      important role in its onset. In this study, skeletal and myocardial muscles were
      examined from human autopsies. Compared to controls (n = 8), doxorubicin-exposed
      hearts (n = 6) showed low absolute enzyme activity of mtDNA-encoded nicotinamide
      adenine dinucleotide hydrogen dehydrogenase (NADH DH, 79% residual activity, p =
      0.03) and cytochrome c oxidase (COX, 59% residual activity, p < 0.001), but not
      of succinate dehydrogenase (SDH), which is encoded exclusively by nuclear DNA.
      NADH DH/SDH and COX/SDH ratios were 37% (p < 0.001) and 27% (p < 0.001) of
      controls. Expression of the mtDNA-encoded subunit II of COX was reduced (82%, p =
      0.04), compared to its unchanged nucleus-encoded subunit IV. MtDNA-content was
      diminished (56%, p = 0.02), but the 'common' mtDNA-deletion was increased (9.2
      fold, p = 0.004). Doxorubicin-exposed hearts harboured numerous additional mtDNA
      rearrangements lacking direct repeats. They contained elevated levels of
      malondialdehyde (MDA) (p = 0.006, compared to controls), which correlated
      inversely with the COX/SDH ratio (r = -0.45, p = 0.02) and the mtDNA-content (r =
      -0.75, p = 0.002), and correlated positively with the levels of the 'common'
      deletion (r = 0.80, p < 0.001). Doxorubicin-exposed hearts also contained the
      highest levels of superoxide (p < 0.001, compared to controls), which correlated
      negatively with the mtDNA-encoded respiratory chain activities, such as the
      COX/SDH ratio (r = -0.57, p = 0.02) and the NADH/SDH ratio (r = -0.52, p = 0.04),
      as well as with the mtDNA content (r = -0.69, p = 0.003), and correlated
      positively with the frequency of the 'common' deletion (r = 0.76, p < 0.001) and
      the MDA levels (r = 0.86, p < 0.001). Doxorubicin-exposed hearts contained
      electron-dense deposits within mitochondria. Hearts exposed to other
      anthracyclines (n = 6) or skeletal muscle (all groups) had no mitochondrial
      dysfunction. Doxorubicin, unlike other anthracyclines, augments lipid
      peroxidation, induces mtDNA mutations and decreases mtDNA content in human
      hearts. These lesions have an impact on mitochondrial function and could be of
      importance in the pathogenesis of clinical cardiomyopathy.

PMID- 16278811
TI  - Conditional deletion of Indian hedgehog from collagen type 2alpha1-expressing
      cells results in abnormal endochondral bone formation.
AB  - Indian hedgehog (Ihh) is actively involved in endochondral bone formation.
      Although expression of Ihh is mostly restricted to pre-hypertrophic chondrocytes,
      the role of chondrocyte-derived Ihh in endochondral bone formation is not
      completely understood. To address such unresolved issues, we used the Cre/loxP
      approach to generate mice (Col2alpha1Cre; Ihhd/Ihhd) in which the Ihh gene was
      selectively ablated from collagen type II expressing cells. Mutant mice were born
      with the expected ratio of Mendelian inheritance, but died shortly after birth
      and were smaller in size, exhibiting malformed and retarded growth of limbs with
      severe skeletal deformities. Alizarin red S staining showed abnormal
      mineralization of axial and appendicular bones. Histological analysis of mutant
      long bones revealed abnormal endochondral bone formation with loss of a normal
      growth plate. In addition, in vivo bromo-deoxyuridine (BrdU) labelling showed a
      marked decrease in chondrocyte proliferation. A delay in chondrocyte hypertrophy
      in Col2alpha1Cre; Ihhd/Ihhd mice was detected by the expression of collagen type
      X and osteopontin, using in situ hybridization. Furthermore, there was no
      expression of bone markers such as collagen type I, bone Gla protein, Runx2/Cbfa1
      or PTH-R in the perichondrium of mutant mice, indicating the absence of
      osteoblasts from endochondral bones. Thus, selective loss of chondrocyte-derived
      Ihh recapitulated the defects in Ihh(-/-) animals, providing direct in vivo
      evidence that Ihh not only regulates chondrocyte proliferation and
      differentiation but also exerts effects on osteoblast differentiation.
      Understanding the exact functions of the molecules involved in endochondral bone
      formation will form the basis for further study to determine the molecular
      mechanisms of skeletal diseases involving various cellular components of bone.

PMID- 16278812
TI  - PD-L2:PD-1 involvement in T cell proliferation, cytokine production, and integrin
      mediated adhesion.
AB  - The B7 family member programmed death ligand 2 (PD-L2) has been implicated in
      both positive and negative regulation of T cell activity. In this study, we
      demonstrate that on human T cells, PD-L2 acts only as a negative regulator of T
      cell activity, inhibiting proliferation, IL-2 production, and IFN-gamma
      production via its interaction with programmed death-1 (PD-1). This study also
      shows a novel role for PD-1 in inhibiting beta1 and beta2 integrin-mediated
      adhesion. PD-L2 inhibition of T cell function involves modulation of the
      phosphoinositide 3-OH kinase (PI 3-K)/AKT and extracellular signal-related kinase
      (ERK)/mitogen-activated protein kinase (MAPK) pathways, with PD-L2 inhibiting
      anti-CD3-induced AKT phosphorylation within minutes and ERK phosphorylation after
      hours. Analysis of phosphatase activity of Src homology 2 domain-containing
      tyrosine phosphatase (SHP)-1 and SHP-2 in response to anti-CD3 mAb or anti-CD3
      mAb + PD-L2 stimulation revealed that while SHP-1 phosphatase activity is not
      affected by stimulation, SHP-2 phosphatase activity is significantly increased by
      anti-CD3 mAb + PD-L2 stimulation. Anti-CD3 mAb + PD-L2 stimulation also increased
      the level of SHP-2 associated with the PD-1 receptor. These results suggest that
      catalytically active SHP-2 associated with the PD-1 receptor is involved in
      modulating T cell function.

PMID- 16278813
TI  - Analysis of Lyn/CD22 double-deficient B cells in vivo demonstrates Lyn- and CD22
      independent pathways affecting BCR regulation and B cell survival.
AB  - B cell fate is determined by the strength of signals from the antigen receptor
      and from co-receptors that adjust the activation threshold and tune the B cell to
      its environment. These co-receptors have been broadly classified into inhibitory
      and enhancing groups, yet some, such as CD22, may have dual effects. CD22
      recruits a variety of signal enhancers at the same time as Lyn-dependent
      phosphorylation leads to the binding of the inhibitory phosphatase SHP-1. To
      assess the relative importance of Lyn- and CD22-dependent and -independent
      pathways, we generated Lyn and CD22 single-deficient mice and Lyn/CD22 double
      deficient mice expressing the MD4 immunoglobulin transgene against hen egg
      lysozyme (IgHEL). This genetic approach has enabled us to compare the
      contributions of Lyn and CD22 to B cell development in vivo, independent of BCR
      specificity and in the presence and absence of self-antigen. Our results show
      that although the effects of Lyn are dominant in negative regulation of B cell
      hyperactivity, Lyn and CD22 have independent and additive effects on B cell
      survival. These findings emphasize the subtle nature of regulation at the BCR and
      the usefulness of genetic complementation to dissect common and parallel
      pathways.

PMID- 16278814
TI  - Requirement of the Fc receptor common gamma-chain for gamma delta T cell-mediated
      promotion of murine experimental autoimmune encephalomyelitis.
AB  - Immunoglobulin Fcgamma receptors (FcgammaR) are comprised of a ligand-binding
      alpha-chain that sometimes associates with a cell signaling common gamma-chain.
      These receptors comprise an important family of effector molecules that link
      humoral and cell-mediated adaptive immunity and regulate innate immunity. Recent
      animal studies suggest that FcgammaR in general, and FcR alpha-chains in
      particular, are required for full development of experimental autoimmune
      encephalomyelitis (EAE). We show here that deletion of the gamma-chain renders
      mice resistant to EAE, whereas deletion of the alpha-chains of FcgammaRI,
      FcgammaRIIB and FcgammaRIII has no protective effect. Susceptibility to EAE is
      fully restored in common gamma-chain-/- mice into which wild-type splenocytes are
      adoptively transferred, but EAE is not restored in common gamma-chain-/- mice
      given wild-type splenocytes depleted of gammadelta T cells. These data indicate
      that although the common gamma-chain is required for full development of EAE in
      mice, this requirement is likely FcgammaR alpha-chain-independent. Expression of
      the common gamma-chain by gammadelta T cells, probably in conjunction with the T
      cell receptor/CD3 complex, is likely the key requirement for full development of
      EAE.

PMID- 16278815
TI  - Methylation of APC, TIMP3, and TERT: a new predictive marker to distinguish
      Barrett's oesophagus patients at risk for malignant transformation.
AB  - Barrett's associated oesophageal adenocarcinoma (EAC) is one of the most rapidly
      increasing malignancies in Western countries. Because of its poor prognosis,
      management of this disease through screening of Barrett's oesophagus (BE)
      patients and identification of those with a high risk of developing an
      adenocarcinoma seems a promising approach. Early molecular markers of malignant
      transformation might contribute to such screening approaches. Gene promoter
      methylation analysis was performed on normal, pre-neoplastic, and neoplastic
      lesions from BE patients. All lesions of interest were sampled by microdissection
      from formalin-fixed paraffin-embedded tissue sections. We found that, in 27
      adenocarcinomas, APC, TIMP3, TERT, CDKN2A, and SFRP1 promoters were methylated in
      93%, 65%, 64%, 48%, and 91%, respectively; in contrast MLH1, RASSF1, RARB, CDH1,
      and FHIT promoters were methylated in less than 5% of the tumours. In BE mucosa
      from patients who had progressed to adenocarcinoma (12 samples), APC, TIMP3, and
      TERT promoters were hypermethylated in 100%, 91%, and 92% of cases, whereas in BE
      mucosa from patients who had not progressed (16 samples) methylation was found
      only in 36%, 23%, and 17%, respectively. Furthermore, the epigenetic profile of
      BE with and without EAC differed significantly with, respectively, 81% and 26% of
      the PCR samples showing promoter hypermethylation for APC, TIMP3, and TERT (p <
      0.0001). Promoter methylation of CDKN2A was infrequently detected in BE samples,
      while SFRP1 methylation was observed in all samples. Our results suggest that
      promoter methylation profiling of BE using multiple target genes including APC,
      TIMP3, and TERT might be used as a predictive marker for increased EAC risk.

PMID- 16278816
TI  - Career choices for pathology: national surveys of graduates of 1974-2002 from UK
      medical schools.
AB  - In the past 10 years there has been increasing concern about recruitment of
      junior doctors into pathology, particularly histopathology, in the UK. In this
      study, we report on career choices for pathology, derived from postal
      questionnaire surveys of all qualifiers from all UK medical schools in nine
      qualification years since 1974. 74% (24,623/33,417) and 73% (20,709/28,468) of
      doctors responded at 1 and 3 years after qualification. The percentage of doctors
      choosing pathology 1 year after qualification has fallen sharply in recent years:
      between 1974 and 1983 it was 4.5% (95% confidence interval 4.1-4.9%) and between
      1993 and 2002 it was 2.3% (CI 2.0-2.5%). 57% of doctors who chose pathology 1
      year after qualification were still working in pathology at year 10. Hours and
      conditions of work, the doctor's personal assessment of their aptitudes, and
      their experience of the subject as a student influenced long-term career choices
      for pathology. Recruitment of UK graduates into the pathology specialties must
      increase to meet demand in the new and expanding subspecialties. This depends on
      developing innovative ways of raising the profile of pathology to medical
      students and junior hospital doctors.

PMID- 16278817
TI  - TGF-beta1 drives partial myofibroblastic differentiation in chondromyxoid fibroma
      of bone.
AB  - Chondromyxoid fibroma (CMF) is a rare benign cartilaginous bone tumour with a
      lobular architecture containing stellate and myofibroblast-like spindle cells.
      The aim of this study was to investigate the presence, spatial distribution, and
      extent of myoid differentiation in CMF and to evaluate a possible causative role
      for TGF-beta1 signalling, which is known to promote smooth muscle actin (SMA)
      expression. Twenty cases were studied for immunoreactivity for muscle-specific
      actin (MSA), SMA, desmin, h-caldesmon, calponin, TGF-beta1, and plasminogen
      activator inhibitor type 1 (PAI-1). The extent of myofibroblastic differentiation
      was further investigated ultrastructurally, including immuno-electron microscopy
      using antibodies against MSA and SMA, focusing upon the different cell types in
      CMF. The expression of potential genes driving this process was quantified by Q
      RT-PCR (TGF-beta1, fibronectin, its EDA splice variant, and PAI-1). Tumour cells,
      especially those with a spindled morphology, showed diffuse immunoreactivity for
      MSA, SMA, TGF-beta1, and PAI-1, while desmin, h-caldesmon, and calponin were
      absent. Ultrastructurally, neoplastic cells showed the presence of myofilaments
      and rare dense bodies, which were more prominent in spindle cells and less so in
      chondroblast-like cells. Immuno-electron microscopy confirmed the actin nature of
      these myofilaments. No fibronexus was identified. The functional activity of TGF
      beta1 was demonstrated by the identification of PAI-1, a related downstream
      molecule both immunohistochemically as well as by Q-RT-PCR. There was a linear
      correlation between TGF-beta1 and PAI-1 expression. Fibronectin-EDA levels were
      low. We have therefore substantiated the presence of morphological,
      immunohistochemical, and immuno-electron microscopic partial myofibroblastic
      differentiation in CMF, driven by TGF-beta1 signalling.

PMID- 16278819
TI  - ILK over-expression in human colon cancer progression correlates with activation
      of beta-catenin, down-regulation of E-cadherin and activation of the Akt-FKHR
      pathway.
AB  - Integrin-linked kinase (ILK) has been implicated in the development and
      progression of several human malignancies. However, the role of ILK in human
      colon cancer progression is not well established, neither have its possible in
      vivo downstream effectors in the disease been identified. We studied, by
      immunohistochemistry, ILK, beta-catenin, E-cadherin, p-Akt and p-FKHR protein
      expression in 125 primary colon carcinomas and 45 corresponding lymph node
      metastases. ILK was expressed in 98.4% of the primary tumours and in 100% of
      metastatic lesions. The levels of ILK expression correlated strongly with tumour
      invasion, tumour grade and stage and were significantly higher in metastatic
      tumours. Activation of beta-catenin, down-regulation of E-cadherin and activation
      of the Akt-FKHR pathway correlated significantly with both ILK expression and
      tumour progression parameters. In conclusion, our results suggest that ILK may
      have an important role in progression of human colon cancer, possibly through in
      vivo regulation of beta-catenin, E-cadherin and Akt pathways. Our study also
      provides some evidence implicating p-FKHR in human colon carcinogenesis and ILK
      signalling.

PMID- 16278818
TI  - Synovial fluid macrophages are capable of osteoclast formation and resorption.
AB  - To determine whether synovial fluid (SF) macrophages isolated from the SF of
      osteoarthritis (OA), rheumatoid arthritis (RA) and pyrophosphate arthropathy
      (PPA) joints are capable of osteoclast formation, and to investigate the cellular
      and humoral factors required for this to occur, SF macrophages (CD14+) were
      isolated from the knee joint SF from patients with OA, RA and PPA and cultured
      for up to 14 days with macrophage-colony stimulating factor (M-CSF) and soluble
      receptor activator for nuclear factor-kappaB ligand (RANKL) or tumour-necrosis
      factor-alpha (TNFalpha) and interleukin-1alpha (IL-1alpha). Osteoclast
      differentiation was assessed by expression of tartrate-resistant acid phosphatase
      (TRAP) and vitronectin receptor (VNR), F-actin ring formation and lacunar
      resorption. Osteoclast formation and lacunar resorption was seen in RANKL-treated
      cultures of SF macrophages isolated from OA, RA and PPA joints with the largest
      amount of resorption noted in RA and PPA SF macrophage cultures. In TNFalpha/IL
      1alpha-treated RA and PPA SF macrophage cultures, osteoclasts capable of lacunar
      resorption were also formed. Lacunar resorption was more extensive in RANKL than
      TNFalpha/IL-1alpha-treated cultures. These findings indicate that SF macrophages
      are capable of differentiating into mature osteoclasts capable of lacunar
      resorption. M-CSF in combination with RANKL or TNFalpha/IL-1alpha was required
      for osteoclast formation. As inflammatory synovial fluids contain an increase in
      the number of macrophages and an increase in the amounts of RANKL, TNFalpha and
      IL-1alpha, these findings suggest that one means whereby bone erosions may form
      in rheumatoid or crystal arthritis is by differentiation of synovial fluid
      macrophages into osteoclasts.

PMID- 16278820
TI  - Iron-free neoplastic nodules and hepatocellular carcinoma without cirrhosis in
      Wistar rats fed a diet high in iron.
AB  - Although excess hepatic iron in hereditary haemochromatosis and dietary iron
      overload in the African causes hepatocellular carcinoma, it usually does so in
      the presence of cirrhosis. A direct hepatocarcinogenic effect of iron has not
      been proved. Moreover, an animal model of hepatocellular carcinoma induced by
      iron overload has not been available. The aim of this study was to develop such a
      model and to use it to ascertain whether excess hepatic iron is directly
      hepatocarcinogenic. Sixty Wistar albino rats were fed a chow diet and 60 the same
      diet supplemented initially with 2% carbonyl iron for 12 months, followed by 0.5%
      ferrocene for 20 months. Five rats from each group were sacrificed every 4 months
      for 24 months for histological and biochemical monitoring. By 16 months,
      hepatocytes in all the rats receiving the iron-supplemented diet showed grade 4
      iron overload, comparable in degree with that seen in patients with advanced
      hereditary haemochromatosis and dietary iron overload. Altered hepatic foci and
      pre-neoplastic nodules were first seen at 16 months. These increased in size and
      number with time, were iron-free, stained positively with placental glutathione
      sulphydryl transferase, and showed the same histological features as the iron
      free foci described in patients with hepatocellular carcinoma complicating
      hereditary haemochromatosis. At 32 months the eight surviving rats in the iron
      overloaded group were sacrificed. The livers of five of these rats contained pre
      neoplastic nodules and one showed, in addition, an iron-free, well-differentiated
      hepatocellular carcinoma. The tumour stained positively for placental glutathione
      sulphydryl transferase. Neither cirrhosis nor portal fibrosis was present in this
      or any iron-loaded animal. We conclude that hepatocellular carcinoma may
      complicate dietary hepatic iron overload in Wistar albino rats in the absence of
      fibrosis or cirrhosis, confirming an aetiological association between dietary
      iron overload and the tumour and suggesting that iron may be directly
      hepatocarcinogenic.

PMID- 16278821
TI  - Inducible nitric oxide synthase activity correlates with lymphangiogenesis and
      vascular endothelial growth factor-C expression in head and neck squamous cell
      carcinoma.
AB  - Nitric oxide (NO) is a diatomic free radical molecule that has been implicated in
      tumour angiogenesis and progression of head and neck squamous cell carcinoma
      (HNSCC). However, the mechanism underlying the effect of NO on tumour spread
      remains largely unknown. Tumour lymphangiogenesis has recently received
      considerable attention and there is increasing evidence that it is relevant for
      metastasis to lymph nodes in HNSCC. Here, we study the correlation between
      inducible NOS synthase (iNOS) activity and lymphangiogenesis in a series of 60
      HNSCCs and the possible involvement of the lymphangiogenic factor vascular
      endothelial growth factor (VEGF)-C. HNSCC presenting with lymph node metastasis
      had a significantly higher lymphatic vessel density in both the tumour mass and
      the peritumour area (p = 0.006 and p = 0.001, respectively). Similarly, tumours
      with lymph node metastasis showed greater lymphatic vessel area than tumours with
      no lymph node involvement (p = 0.001 for intratumour lymphatics and p < 0.001 for
      peritumour lymphatics). iNOS activity measured in specimens from the tumour
      periphery correlated strongly with both lymphatic vessel density and lymphatic
      vessel area (p = 0.01, rs = 0.45 and p < 0.001, rs = 0.725, respectively).
      Conversely, these correlations were not observed in specimens from the tumour
      core. In addition, VEGF-C mRNA expression was significantly elevated in tumours
      with high iNOS activity (p = 0.008, rs = 0.563), and VEGF-C expression correlated
      positively with the presence of lymph node metastases (p = 0.03). In vitro, in
      the A431 human squamous carcinoma cell line, exogenous and endogenous stimulation
      of the iNOS pathway led to up-regulation of VEGF-C, which was blocked by the NOS
      inhibitor L-NNA. Taken together, our results indicate that iNOS activity may
      promote lymphangiogenesis and spread to lymph nodes in HNSCC, with the possible
      involvement of VEGF-C.

PMID- 16278822
TI  - Role of metalloproteinases MMP-9 and MT1-MMP in CXCL12-promoted myeloma cell
      invasion across basement membranes.
AB  - Malignant plasma cells in multiple myeloma home to the bone marrow (BM),
      accumulate in different niches and, in late disease, migrate from the BM into
      blood. These migratory events involve cell trafficking across extracellular
      matrix (ECM)-rich basement membranes and interstitial tissues. Metalloproteinases
      (MMP) degrade ECM and facilitate tumour cell invasion. The chemokine CXCL12 is
      expressed in the BM, and it was previously shown that it triggers myeloma cell
      migration and activation. In the present work we show that CXCL12 promotes
      myeloma cell invasion across Matrigel-reconstituted basement membranes and type I
      collagen gels. MMP-9 activity was required for invasion through Matrigel towards
      CXCL12, whereas TIMP-1, a MMP-9 inhibitor that we found to be expressed by
      myeloma and BM stromal cells, impaired the invasion. In addition, we show that
      the membrane-bound MT1-MMP metalloproteinase is expressed by myeloma cells and
      contributes to CXCL12-promoted myeloma cell invasion across Matrigel. Increase in
      MT1-MMP expression, as well as induction of its membrane polarization by CXCL12
      in myeloma cells, might represent potential mechanisms contributing to this
      invasion. CXCL12-promoted invasion across type I collagen involved
      metalloproteinases different from MT1-MMP. These data indicate that CXCL12 could
      contribute to myeloma cell trafficking in the BM involving MMP-9 and MT1-MMP
      activities.

PMID- 16278823
TI  - Mutation, selection, and evolution of the Crohn disease susceptibility gene
      CARD15.
AB  - Three common mutations in the CARD15 (NOD2) gene are known to be associated with
      susceptibility to Crohn disease (CD), and genetic data suggest a gene dosage
      model with an increased risk of 2-4-fold in heterozygotes and 20-40-fold in
      homozygotes. However, the discovery of numerous rare variants of CARD15 indicates
      that some heterozygotes for the common mutations have a rare mutation on the
      other CARD15 allele, which would support a recessive model for CD. We addressed
      this issue by screening CARD15 for mutations in 100 CD patients who were
      heterozygous for one of the three common mutations. We also developed a strategy
      for evaluating potential disease susceptibility alleles (DSAs) that involves
      assessing the degree of evolutionary conservation of involved residues, predicted
      effects on protein structure and function, and genotyping in a large sample of
      cases and controls. The evolutionary analysis was aided by sequencing the entire
      coding region of CARD15 in three primates (chimp, gibbon, and tamarin) and
      aligning the human sequence with these and orthologs from other species. We found
      that 11 of the 100 CD patients screened had a second potential pathogenic
      mutation within the exonic and periexonic sequences examined. Assuming that there
      are no additional pathogenic mutations in noncoding regions, our study suggests
      that most carriers of the common DSAs are true heterozygotes, and supports
      previous evidence for a gene dosage model. Four novel nonsynonymous mutations
      were detected, one of which would produce premature termination of translation
      c.2686C>T (p.Arg896X). Two potential DSAs--c.2107C>T (p.Arg703Cys) and g.2238T>A
      (c.74-7T>A)--were significantly associated with CD in the case control sample.
      Analysis of the evolution of CARD15 revealed strong conservation of the encoded
      protein, with identity to the human sequence ranging from 99.1% in the chimp to
      44.5% in fugu. Higher primates possess an open reading frame (ORF) upstream of
      the putative initiation site in other species that encodes a further 27 N
      terminal amino acids, while four regions of high conservation are observed
      outside of the known domains of CARD15, indicative of additional residues of
      functional importance. The strategy developed here may have general application
      to the assessment of mutation pathogenicity and genetic models in other complex
      disorders.

PMID- 16278824
TI  - The UMD TP53 database and website: update and revisions.
AB  - Mutation of the p53 gene is the most frequent genetic alteration found in human
      cancer, but it is also the most frequently reported with more than 22,000
      mutations published in 2,000 papers. In 1991, we developed a database and
      software to handle and analyze all this information. The database has been widely
      used for clinical analysis and molecular epidemiology. We have expanded the scope
      of the database by integrating structural, phylogenetic and biological
      information on wild-type (wt) and mutant TP53. Integration of the TP53 mutant
      activity database provides unique information that will be useful to both
      clinicians and scientists. All of this information is available from a new
      website (www.umd.be:2072/) that will generate a detailed informative page for
      every TP53 mutant in the database. New tools to check TP53 mutations and minimize
      errors found in the literature are also available.

PMID- 16278825
TI  - Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis:
      molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A.
AB  - Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal-recessive
      disease that affects young children. It presents as a severe hyperinflammatory
      syndrome with activated macrophages and T lymphocytes. Mutations in the perforin
      1 gene (PRF1) were found in FHL-2 in 15-50% of all cases. Defective granule
      exocytosis caused by mutations in the hMunc13-4 gene (UNC13D) has been described
      in FHL-3. FHL-4 patients have mutations in STX11, a t-SNARE involved in
      intracellular trafficking. We analyzed a large group of 63 unrelated patients
      with FHL of different geographic origins (Turkey:32; Germany:23; others:8) for
      mutations in STX11, PRF1, and UNC13D. We identified mutations in 38 samples (20
      in PRF1, 12 in UNC13D, and six in STX11). Of 32 patients from Turkey, 14 had
      mutations in PRF1, six had mutations in UNC13D, and six had mutations in STX11.
      The mutation Trp374X in PRF1 was found in 12 patients from Turkey and was
      associated with a very early onset of the disease below the age of 3 months in
      all cases. In contrast, three of 23 and four of 23 patients from Germany, and
      three of eight and two of eight from other origins showed mutations in PRF1 and
      UNC13D, respectively, but none in STX11. Thus, FHL-2, FHL-3, and FHL-4 account
      for 80% of the HLH cases of Turkish origin, and for 30% of German patients.
      Furthermore, we identified mutations in RAB27A in three patients with FHL-related
      Griscelli syndrome type 2. In functional studies using a mammalian two-hybrid
      system we found that missense mutations Ala87Pro in Rab27a and Leu403Pro in
      hMunc13-4 each prevented the formation of a stable hMunc13-4/Rab27a complex in
      vitro. Our findings demonstrate extensive genetic and allelic heterogeneity in
      FHL and delineate an approach for functionally characterizing missense mutations
      in RAB27A and UNC13D.

PMID- 16278826
TI  - Cryptic haplotypes of SERPINA1 confer susceptibility to chronic obstructive
      pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and
      morbidity worldwide. While cigarette smoking is a major cause of COPD, only 15%
      of smokers develop the disease, indicating major genetic influences. The most
      widely recognized candidate gene in COPD is SERPINA1, although it has been
      suggested that SERPINA3 may also play a role. To detect cryptic genetic variants
      that might contribute to disease, we identified 15 SNP haplotype tags from high
      density SNP maps of the two genes and evaluated these SNPs in the largest case
      control genetic study of COPD conducted so far. For SERPINA1, six newly
      identified haplotypes with a common backbone of five SNPs were found to increase
      the risk of disease by six- to 50-fold, the highest risk of COPD reported to
      date. In contrast, no haplotype associations for SERPINA3 were identified.

PMID- 16278827
TI  - Dihaloindium hydride as a novel reducing agent.
AB  - Dihaloindium hydrides (X2InH) are novel reducing reagents, which act in both an
      ionic and a radical manner. The hydrides were easily generated from InX3 and
      Bu3SnH to reduce a variety of functionalities such as aldehydes, ketones, enones,
      and imines. The combination of a phosphine and Cl2InH accomplished the selective
      transformation from acid chlorides to aldehydes. One-pot treatment of Cl2InH,
      enones, and aldehydes achieved reductive aldol reactions, in which the
      predominant reduction of enones was followed by an aldol reaction between the
      resulting indium enolates and the remaining aldehydes. It is noteworthy that both
      anti- and syn-selective aldols were obtained by the use of THF and an aqueous
      solvent, respectively. The replacement of Bu3SnH with Et3SiH as a hydride source
      allowed the catalytic use of InBr3 to give the syn-selective aldols. The
      dehalogenation of alkyl halides was achieved by a catalytic amount of InCl3 in
      the presence of Bu3SnH. This procedure was applied to some representative
      cyclizations as radical proof. A simple and non-toxic system, NaBH4/InCl3, also
      promoted dehalogenation, intramolecular cyclization, and intermolecular coupling
      reactions. In addition, the Et3SiH/InCl3 system was found applicable to an
      effective intramolecular cyclization of enynes.

PMID- 16278829
TI  - Chromatographic analysis of allosteric effects between ibuprofen and
      benzodiazepines on human serum albumin.
AB  - The effects of (R)- and (S)-ibuprofen on the binding of benzodiazepines to human
      serum albumin (HSA) were examined by biointeraction chromatography. The
      displacement of benzodiazepines from HSA by (R)- and (S)-ibuprofen was found to
      involve negative allosteric interactions (or possible direct competition) for
      most (R)-benzodiazepines. However, (S)-benzodiazepines gave positive or negative
      allosteric effects and direct competition when displaced by (R)- or (S)
      ibuprofen. Association equilibrium constants and coupling constants measured for
      these effects indicated that they involved two classes of ibuprofen binding
      regions (i.e., low- and high-affinity sites). Based on these results, a model was
      proposed to explain the binding of benzodiazepines to HSA and their interactions
      with ibuprofen. This model gave good agreement with previous reports examining
      the binding of benzodiazepines to HSA.

PMID- 16278830
TI  - Molecular dynamics simulation studies of a protein-RNA complex with a selectively
      modified binding interface.
AB  - The RNA recognition motif (RRM) is one of the most common RNA binding domains. We
      have investigated the contribution of three highly conserved aromatic amino acids
      to RNA binding by the N-terminal RRM of the U1A protein. Recently, we synthesized
      a modified base (A-4CPh) in which a phenyl group is tethered to adenine using a
      linker of 4 methylene groups. The substitution of this base for adenine in the
      target RNA selectively stabilizes the complex formed with a U1A protein in which
      one of the conserved aromatic amino acids is replaced with Ala (Phe56Ala). In
      this article, we report molecular dynamics (MD) simulations that probe the
      structural consequences of the substitution of A-4CPh for adenine in the wild
      type and Phe56Ala U1A-RNA complexes and in the free RNA. The simulations suggest
      that A-4CPh stabilizes the complex formed with Phe56Ala by adopting a folded
      conformation in which the tethered phenyl group fills the site occupied by the
      phenyl group of Phe56 in the wild-type complex. In contrast, an extended
      conformation of A-4CPh is predicted to be most stable in the complex formed with
      the wild-type protein. The calculations indicate A-4CPh is in an extended
      conformation in the free RNA. Therefore, preorganizing the structure of the
      phenyl-tethered base for binding may improve both the affinity and specificity of
      the RNA containing A-4CPh for the Phe56Ala U1A protein. Taken together, the
      previous experimental work and the calculations reported here suggest a general
      design strategy for altering RRM-RNA complex stability.

PMID- 16278831
TI  - Electrostatic properties of cowpea chlorotic mottle virus and cucumber mosaic
      virus capsids.
AB  - Electrostatic properties of cowpea chlorotic mottle virus (CCMV) and cucumber
      mosaic virus (CMV) were investigated using numerical solutions to the Poisson
      Boltzmann equation. Experimentally, it has been shown that CCMV particles swell
      in the absence of divalent cations when the pH is raised from 5 to 7. CMV,
      although structurally homologous, does not undergo this transition. An analysis
      of the calculated electrostatic potential confirms that a strong electrostatic
      repulsion at the calcium-binding sites in the CCMV capsid is most likely the
      driving force for the capsid swelling process during the release of calcium. The
      binding interaction between the encapsulated genome material (RNA) inside of the
      capsid and the inner capsid shell is weakened during the swelling transition.
      This probably aids in the RNA release process, but it is unlikely that the RNA is
      released through capsid openings due to unfavorable electrostatic interaction
      between the RNA and capsid inner shell residues at these openings. Calculations
      of the calcium binding energies show that Ca(2+) can bind both to the native and
      swollen forms of the CCMV virion. Favorable binding to the swollen form suggests
      that Ca(2+) ions can induce the capsid contraction and stabilize the native form.

PMID- 16278833
TI  - Normal lymphocytes from leukemic samples as an internal quality control for
      fluorescence intensity in immunophenotyping of acute leukemias.
AB  - BACKGROUND: Multiparametric flow cytometry has become an indispensable but
      complex tool for the diagnosis of acute leukemias. Interpretation of
      immunophenotypic data within a six-parameter analytical space relies on the
      standardization and validation of the instrument, the reagents, and the
      procedure. To address whether or not residual normal lymphocytes, usually present
      within leukemic samples, can serve as internal quality control for fluorescence
      intensity, 116 leukemic and 35 normal samples were analyzed. METHODS: Eight
      laboratories participated in the study and recruited a total of 151 individuals
      including 29 patients with B-cell precursor acute lymphoblastic leukemia (BCP
      ALL), 77 with acute myeloid leukemia (AML), 10 with T-cell precursor acute
      lymphoblastic leukemia (T-ALL), and 35 normal bone marrow donors. Lymphocytes
      were gated according to the CD45hi/SSClo gating strategy, after which median
      fluorescence intensities (MFI) as well as percentages of positive cells
      (%positive) for CD19, CD22, CD7, and CD3 were recorded. Nonparametric statistics
      were used to compare variation within and between laboratories. RESULTS: Normal
      lymphocytes within leukemic samples do not show substantial differences compared
      to lymphocytes from normal controls with respect to expression of CD19, CD22,
      CD7, and CD3. In particular, longitudinal control charts of MFI values for CD3
      antigen provide useful information on analytical and instrument performance.
      CONCLUSION: Residual normal lymphocytes can serve as internal quality control for
      studies addressing fluorescence intensity in the setting of immunophenotyping of
      acute leukemias.

PMID- 16278832
TI  - Body dysmorphic disorder and social phobia: cross-sectional and prospective data.
AB  - Much attention has been paid to the relationship between body dysmorphic disorder
      (BDD) and obsessive-compulsive disorder (OCD). However, to our knowledge, no
      published study has focused directly on the relationship between BDD and social
      phobia (SP). This is striking given similar clinical features of the two
      disorders, data showing elevated comorbidity between them, and Eastern
      conceptualizations of BDD as a form of SP. In this study, 39.3% of 178
      individuals with current BDD had comorbid lifetime SP, and 34.3% had current SP.
      SP onset was typically before BDD. Individuals with BDD, with and without
      lifetime SP, were similar on many general characteristics (e.g., age of BDD
      onset, gender distribution, BDD severity, overall functional disability).
      However, subjects with BDD+SP were significantly less likely to be employed, were
      more likely to report lifetime suicidal ideation, and had poorer global social
      adjustment on one of two measures. Both BDD and SP were associated with elevated
      social anxiety; subjects with BDD+SP experienced additional social anxiety that
      appeared independent of BDD symptoms. Examining 1-year prospective data available
      for 161 subjects, BDD+SP subjects were somewhat less likely to experience
      remission (partial or full) of their BDD symptoms over 1-year follow-up, although
      this difference was not statistically significant (hazard ratio = .64, P = .18).
      In summary, these findings, including elevated rates of SP in patients with BDD,
      highlight a need for additional research on the relationship between BDD and SP.

PMID- 16278834
TI  - Natural and edible biopolymer poly-gamma-glutamic acid: synthesis, production,
      and applications.
AB  - Poly-gamma-glutamic acid (gamma-PGA) is a very promising biodegradable polymer
      that is produced by Bacillus subtilis. Gamma-PGA is water-soluble, anionic,
      biodegradable, and edible. This paper reviews the production of a strain of gamma
      PGA and recent developments with respect to applications in terms of Ca
      absorption, moisturizing properties, gamma-PGA conjugation, super absorbent
      polymer, and so on. Our recent research shows that gamma-PGA can be used as an
      immune-stimulating and anti-tumor agent, especially at high molecular weight.

PMID- 16278835
TI  - Assimilation, dissimilation, and detoxification of formaldehyde, a central
      metabolic intermediate of methylotrophic metabolism.
AB  - Methanol is a valuable raw material used in the manufacture of useful chemicals
      as well as a potential source of energy to replace coal and petroleum.
      Biotechnological interest in the microbial utilization of methanol has increased
      because it is an ideal carbon source and can be produced from renewable biomass.
      Formaldehyde, a cytotoxic compound, is a central metabolic intermediate in
      methanol metabolism. Therefore, microorganisms utilizing methanol have adopted
      several metabolic strategies to cope with the toxicity of formaldehyde.
      Formaldehyde is initially detoxified through trapping by some cofactors, such as
      glutathione, mycothiol, tetrahydrofolate, and tetrahydromethanopterin, before
      being oxidized to CO2. Alternatively, free formaldehyde can be trapped by sugar
      phosphates as the first reaction in the C1 assimilation pathways: the xylulose
      monophosphate pathway for yeasts and the ribulose monophosphate (RuMP) pathway
      for bacteria. In yeasts, although formaldehyde generation and consumption takes
      place in the peroxisome, the cytosolic formaldehyde oxidation pathway also plays
      a role in formaldehyde detoxification as well as energy formation. The key
      enzymes of the RuMP pathway are found in a variety of microorganisms including
      bacteria and archaea. Regulation of the genes encoding these enzymes and their
      catalytic mechanisms depend on the physiological traits of these organisms during
      evolution.

PMID- 16278836
TI  - Unsymmetric bidentate ligands in metal-catalyzed carbonylation of alkenes.
AB  - Characteristic features of unsymmetric bidentate ligands, in which the two
      coordination atoms are not equivalent, are reviewed with a focus on their use in
      metal-catalyzed olefin carbonylations. High enantioselectivity for a variety of
      substrates was achieved using ligand 9 in Rh-catalyzed hydroformylation.
      Unsymmetric ligand 21e shows high productivity accompanied by high regio- and
      enantioselectivities in the Pd-catalyzed alternating copolymerization of 1-alkene
      with CO. The advantages of electronic unsymmetry are demonstrated especially in
      the spectroscopic observation of single steps involved in catalytic cycles.

PMID- 16278837
TI  - Cross-linking chemistry and biology: development of multifunctional photoaffinity
      probes.
AB  - An efficient method of photoaffinity labeling has been developed based on
      rationally designed multifunctional photoprobes. Photoaffinity techniques have
      been used to elucidate the protein structure at the interface of biomolecules by
      the photochemical labeling of interacting sites. However, the identification of
      labeled sites within target proteins is often difficult. Novel biotinyl bioprobes
      bearing a diazirine photophore have contributed significantly to the rapid
      elucidation of ligand binding sites within proteins, thereby extending
      conventional photoaffinity methods. This article discusses the synthesis and
      applications of various photoprobes bearing a biotin, including strategies using
      cleavable linkages between photophores. The combination of photoaffinity methods
      with chip technology is also described as a novel entry to rapid affinity-based
      screening of inhibitors. This review focuses on a rapid and reliable
      photoaffinity method utilizing diazirine-based multifunctional photoprobes with
      numerous potential applications in functional proteomics of biomolecular
      interactions.

PMID- 16278838
TI  - Rh2[MTPA]4, a dirhodium complex as NMR auxiliary for chiral recognition.
AB  - The dirhodium complex Rh(+II)2[(+)-MTPA]4 is introduced as an NMR auxiliary for
      enantiodifferentiation. As a soft Lewis acid, it is particularly useful for the
      recognition of soft Lewis base molecules. The donor properties of ligands can be
      divided into several categories and are exemplified by various classes of
      phosphorus-containing functionalities. In addition, the thermodynamics of the
      underlying ligand-complex equilibria are discussed and stereochemical
      implications demonstrated. The extension of the dirhodium method to absolute
      configuration determination is evaluated. The outlook for future applications
      with further non-phosphorus ligands is presented.

PMID- 16278839
TI  - Discovery and development of microporous metal carboxylates.
AB  - We have found a form of copper(II) terephthalate that occluded an enormous amount
      of gases such as N2, Ar, O2, and Xe. Copper(II) terephthalate is the first metal
      complex found capable of adsorbing gases. This complex has opened a new field of
      adsorbent chemistry and is recognized as a leader in the construction of
      microporous metal complexes. In extending the route for the synthesis of
      microporous complexes, we obtained many new porous materials that are widely
      recognized as useful materials for applications in areas such as gas storage,
      molecular sieves, catalysis, inclusion complexes, and surface science.

PMID- 16278840
TI  - In vivo butyrylcholinesterase activity is not increased in Alzheimer's disease
      synapses.
AB  - OBJECTIVE: We tested the premise that cholinesterase inhibitor therapy should
      target butyrylcholinesterase (BuChE) in Alzheimer's disease (AD), not
      acetylcholinesterase (AChE) alone, because both enzymes hydrolyze acetylcholine,
      and BuChE is increased in AD cerebral cortex. METHODS: To examine this issue in
      vivo, we quantified human cerebral cortical BuChE activity using tracer kinetic
      estimates (k(3)) of 1-[(11)C]methyl-4-piperidinyl n-butyrate ([(11)C]BMP)
      hydrolysis determined by positron emission tomography. Validation of the putative
      positron emission tomography method included regional distribution, positive
      correlation with age, and attenuation by the nonselective cholinesterase
      inhibitor physostigmine, but no attenuation by the AChE-selective inhibitor
      donepezil. Positron emission tomography scans in AD patients (n = 15) and control
      subjects (n = 12) measured both BuChE (using [(11)C]BMP) and AChE activity (using
      N-[(11)C] methylpiperidin-4-yl propionate, an established method). RESULTS: As
      expected, AChE activity in AD cerebral cortex was decreased to 75 +/- 13% of
      normal (p = 0.00001). Contrary to prediction, accompanying BuChE activity also
      was decreased to 82 +/- 14% of normal (p = 0.001). INTERPRETATION: Failure to
      observe increased [(11)C]BMP hydrolysis in vivo makes it less likely that
      incremental BuChE contributes importantly to acetylcholine hydrolysis in AD. The
      findings do not support the premise that inhibitor therapy should target BuChE so
      as to prevent increased levels of BuChE from hydrolyzing acetylcholine in AD
      cerebral cortex.

PMID- 16278841
TI  - Rapid eye movement sleep behavior disorder and potassium channel antibody
      associated limbic encephalitis.
AB  - Of six patients registered in our center with nonparaneoplastic limbic
      encephalitis associated with antibodies to voltage-gated potassium channels, the
      five men had rapid eye movement sleep behavior disorder (RBD) coincident with
      voltage-gated potassium channel antibody-associated limbic encephalitis onset. In
      three patients, immunosuppression resulted in resolution of RBD in parallel with
      remission of the limbic syndrome. RBD persisted in two patients with partial
      resolution of the limbic syndrome. Our findings suggest that RBD is frequent in
      the setting of voltage-gated potassium channel antibody-associated limbic
      encephalitis and can be related to autoimmune-mediated mechanisms. In addition,
      these observations suggest that impairment of the limbic system may play a role
      in the pathogenesis of RBD.

PMID- 16278842
TI  - A novel processing method for injection-molded polyether-urethane scaffolds. Part
      2: cellular interactions.
AB  - A large-scale scaffold processing method with injection molding has been
      successfully developed. Water was used as a foaming agent for the new technique.
      NaCl was used as a porogen to achieve an open-cell structure. Organic solvents,
      which are common foaming agents for polyurethane, where not used. Toxic remains
      in the polymer were therefore prevented. Biocompatibility tested gave a mean
      optical density of 81% from WST-1 proliferation assay. In comparison to the
      previously study processing method, hot pressing (Haugen H, Ried V, Brunner M,
      Will J, Wintermantel E. J Mater Sci: Mater Med2004;15:343-346), the current
      scaffolds had an increase of 20% of the mean optical density. Cell seeding showed
      that human fibroblasts adhered to the surface and proliferated. The spread of the
      adhered fibroblasts was uniform on the surface. A quantitative MTT analysis
      proved that there was a significant (p < 0.01) increase in the OD level after 7
      and 14 days of incubation. This cell layer thickened with increased incubation
      time from 7 to 14 days (p < 0.05) and had typical fibroblast morphology.

PMID- 16278844
TI  - Nanoindentation of dental composites.
AB  - The intent of this project was to evaluate the elastic modulus and hardness of
      four composites with different fillers, a microfill, a hybrid, a dental resin
      cement, and a fiber filler, using nanoindentation. An indentation load of 0.001 N
      was used and 100 indents per specimen were taken. The elastic modulus measured
      for the Choice composite was 30.2-30.3 GPa, 15.9-16.0 GPa for Micronew, 24.6-27.1
      GPa for Renew, and 36.4-47.1 GPa for Restolux. The statistical analysis indicated
      a significant difference in the elastic modulus for all four composites. Micronew
      had the lowest hardness (1.2-1.3 GPa) followed by Renew (1.6-1.8 GPa), Choice
      (2.6-2.8 GPa), and Restolux (2.7-4.0 GPa). The statistical analysis indicated a
      significant difference between Choice and Restolux from Micronew and Renew, with
      Renew and Micronew not being significantly different from each other.
      Nanoindentation of dental composites, using a 10 x 10 matrix of indentations,
      resulted in a wide range of measured values for the elastic modulus and hardness
      because of the size of the filler particle, the location of the indenter within
      the filler particle, the composition of the filler particles, and the location of
      the indenter within the filler/resin matrix.

PMID- 16278843
TI  - Stair ascent kinematics affect UHMWPE wear and damage in total knee replacements.
AB  - Investigations were performed to characterize the wear patterns of tibial inserts
      in a load-controlled knee simulator by incorporating both normal gait and
      clinically acquired stair climbing kinematics and load conditions. Two different
      tibial insert designs were evaluated: the NexGen Cruciate Retaining Augmentable
      and NexGen Legacy Posterior Stabilized inserts. Two test conditions were run:
      standard gait only, and gait with bouts of stair climbing at a ratio of 70:1.
      Gravimetric wear measurements, damage and contact area assessments, and kinematic
      evaluations were performed. The addition of stair climbing kinematics
      significantly affected the wear behavior. Regardless of design, wear rates for
      standard gait tests were significantly higher than those that included bouts of
      stair climbing. The damage modes seen in both test conditions were primarily
      burnishing with secondary scratching and pitting. At 2 Mc, the damage areas were
      not significantly different between the two designs, but the damage area with
      stair climbing was significantly larger than that with gait alone. The fact that
      even small bouts of an additional activity of daily living could markedly impact
      wear simulator results calls into question the usefulness of studies that rely
      solely on kinematics and load inputs assumed from level gait.

PMID- 16278845
TI  - Nanofiber generation of hydroxyapatite and fluor-hydroxyapatite bioceramics.
AB  - In this study, we produced hydroxyapatite (HA) and fluor-hydroxyapatite (FHA)
      bioceramics as a novel geometrical form, the nanoscale fiber, for the biomedical
      applications. Based on the sol-gel precursors of the apatites, an electrospinning
      technique was introduced to generate nanoscale fibers. The diameter of the fibers
      was exploited in the range of a few micrometers to hundreds of nanometers (1.55
      microm-240 nm) by means of adjusting the concentration of the sols. Through the
      fluoridation of apatite, the solubility of the fiber was tailored and the
      fluorine ions were well released from the FHA. The HA and FHA nanofibers produced
      in this study are considered to find potential applications in the biomaterials
      and tissue engineering fields.

PMID- 16278846
TI  - Design and delivery of silver sulfadiazine from alginate microspheres-impregnated
      collagen scaffold.
AB  - A reconstituted collagen scaffold impregnated with silver sulfadiazine (SSD)
      loaded alginate microspheres, capable of delivering the drug in a controlled
      manner has been developed. SSD-loaded alginate microspheres were prepared by
      modified water-in-oil emulsion technique through interfacial ionic gelation of
      alginate using CaCl2. The SSD-loaded microspheres were impregnated in pepsin
      solubilized collagen, in situ, while inducing fibrillation and cast as thin
      scaffold. Morphological features of microspheres and microsphere-impregnated
      collagen were analyzed through SEM. Distribution homogeneity of impregnated
      microspheres, their in vitro behavior in (Dulbecco's modified minimal essential
      media) DMEM, and antibacterial efficiency against ATCC pathogens were determined.
      Initial drug load of 20% (w/w) with respect to alginate and 40% (v/v) of 2%
      alginate with respect to oil phase were found to produce microspheres of optimum
      drug entrapment (3%) and required size range (300-370 microm). In vitro drug
      release studies from the scaffold showed an initial burst release of 47.5% and a
      controlled release for 72 h with equilibrium concentration of 68.8%. SSD-loaded
      microspheres exhibited minimal inhibitory concentration (MIC) and minimal
      bactericidal concentration (MBC) levels of 32 and 40.2 microg/mL to both K.
      pneumoniae and E. coli respectively. P. aeruginosa showed MIC and MBC levels of
      44.8 and 51.2 microg/mL respectively, while Staphylococcus aureus exhibited MIC
      and MBC at the same concentration range (57.6 microg/mL). The collagen-based
      scaffold impregnated with SSD-loaded alginate microspheres can deliver SSD in a
      controlled fashion, can control infection for extended time period with lesser
      dressing frequencies, and will enable easier assessment of wound.

PMID- 16278848
TI  - Role of fluid dynamics on the healing of an in vivo tissue engineered vascular
      graft.
AB  - A polyester (PET) reinforced fibrin-FN-VEGF-TGFbeta vascular graft, formed by a
      four-step preclotting technique of a porous PET arterial graft, shows the
      overlapping inflammation, proliferation, and remodeling steps of normal wound
      healing when implanted in the descending thoracic aorta (DTA) position in the
      dog, forming a surface layer of endothelial cells. While the DTA grafts readily
      healed (i.e., endothelialized), similar grafts implanted in the carotid-femoral
      artery position did not fully heal. Since the initial phases of healing were
      shown to be dependent upon the transport of blood-borne constituents to the graft
      surface, the extent of healing appears to be dependent on the fluid dynamics
      present in the artery-graft-artery construct. The length of the noncompliant
      graft, the construction of the anastomoses, bends in the construct, graft
      diameter, and graft compliance can affect the fluid dynamics in the implant, and
      thus the healing of the graft. This has clinical relevance for the testing and
      development of new vascular graft materials.

PMID- 16278849
TI  - In-vitro leakage susceptibility of tracheoesophageal shunt prostheses in the
      absence and presence of a biofilm.

PMID- 16278851
TI  - Gelatin-based biomimetic tissue adhesive. Potential for retinal reattachment.
AB  - An adhesive that cures under moist/wet conditions could facilitate surgical
      procedures for retinal reattachment. We are investigating an adhesive that mimics
      the factor XIIIa-mediated crosslinking of fibrin that occurs in the late stages
      of the blood coagulation cascade. Specifically, we use gelatin as the structural
      protein (in place of fibrin), and crosslink gelatin using a calcium-independent
      microbial transglutaminase (in place of the calcium-dependent transglutaminase
      factor XIIIa). Injection of gelatin and microbial transglutaminase (mTG) into the
      vitreous cavity of Sprague Dawley white rats did not elicit structural or
      cellular damage to the retina as evidenced from histological evaluation 2 weeks
      post-injection. Qualitative in vitro studies indicate that the gelatin-mTG
      adhesive binds to bovine retinal tissue under wet conditions. Quantitative lap
      shear tests were performed with more robust bovine tissue from the choroid and
      sclera. The lap-shear strength of the biomimetic gelatin-mTG adhesive was
      independent of tissue-type and ranged from 15 to 45 kPa, which is comparable to
      the values reported for other soft-tissue adhesives. These studies suggest that
      the mTG-crosslinked gelatin may provide a simple, safe, and effective adhesive
      for ophthalmic applications.

PMID- 16278850
TI  - Microstructure and corrosion behavior of porous coatings on titanium alloy by
      vacuum-brazed method.
AB  - The microstructural evolution and electrochemical characteristics of brazed
      porous-coated Ti-6Al-4V alloy were analyzed and compared with respect to the
      conventionally 1300 degrees C sintering method. The titanium filler metal of low
      melting-point (934 degrees C) Ti-15Cu-15Ni was used to braze commercially pure
      (CP) titanium beads onto the substrate of Ti-6Al-4V alloy at 970 degrees C for 2
      and 8 h. Optical microscopy, scanning and transmission electron microscopy, and X
      ray diffractometry (XRD) were used to characterize the microstructure and phase
      of the brazed metal; also, the potentiostat was used for corrosion study.
      Experimental results indicate that the bead/substrate contact interface of the
      970 degrees C brazed specimens show larger contact area and higher radius
      curvature in comparison with 1300 degrees C sintering method. The microstructure
      of brazed specimens shows the Widmanstatten structure in the brazed zone and
      equiaxed alpha plus intergranular beta in the Ti-6Al-4V substrate. The
      intermetallic Ti2Ni phase existing in the prior filler metal diminishes, while
      the Ti2Cu phase can be identified for the substrate at 970 for 2 h, but the
      latter phase decrease with time. In Hank's solution at 37 degrees C, the
      corrosion rates of the 1300 degrees C sintering and the 970 degrees C brazed
      samples are similar at corrosion potential (E(corr)) in potentiodynamic test, and
      the value of E(corr) for the brazed sample is noble to the sintering samples. The
      current densities of the brazed specimens do not exceed 100 microA/cm2 at 3.5 V
      (SCE). These results suggest that the vacuum-brazed method exhibits the
      potentiality to manufacture the porous-coated specimens for biomedical
      application.

PMID- 16278852
TI  - Pyruvate carboxylase deficiency: metabolic characteristics and new neurological
      aspects.
AB  - OBJECTIVE: Pyruvate carboxylase (PC) deficiency is a rare metabolic disease.
      Recently, therapeutic possibilities have been introduced. We aimed to report the
      largest series of the B type of PC deficiency, focusing on some neurological
      aspects that have not yet been documented. METHODS: We retrospectively studied
      nine patients with the severe neonatal form of PC deficiency diagnosed in our
      hospital. Detailed clinical features, brain imaging, biochemical characteristics,
      and global outcome are reported. RESULTS: All patients had axial hypotonia and
      tachypnea during the first hours of life. The initial level of consciousness was
      preserved in most patients. Abnormal movements (high-amplitude tremor and
      hypokinesia) and bizarre ocular behavior were the most common findings, whereas
      epilepsy was infrequent. Brain magnetic resonance imaging mostly disclosed cystic
      periventricular leukomalacia. Hypoglycemia, lactic acidosis, and
      hypercitrullinemia were invariably found. Hyperammoniemia, hypernatremia, and
      high proline and lysine were frequently detected. A rapid fatal outcome was
      observed in most patients. INTERPRETATION: Clinical and biochemical
      characteristics of this deficiency are highly suggestive. Abnormal movements such
      as rigidity and hypokinesia (hypokinetic-rigid syndrome) are an important
      hallmark and may orientate to PC deficiency when associated with severe lactic
      acidosis.

PMID- 16278853
TI  - APOE epsilon4 is not associated with Alzheimer's disease in elderly Nigerians.
AB  - Since 1992, research teams from Indiana University and the University of Ibadan
      have been collecting and comparing data from two diverse, elderly populations to
      identify risk factors for dementia and Alzheimer's disease. Apolipoprotein E
      (APOE) was genotyped in 2,245 Nigerian samples. Of these, 830 had a diagnosis:
      459 were normal, and 140 had dementia including 123 diagnosed with Alzheimer's
      disease. In contrast with other populations, the APOE epsilon4 allele was not
      significantly associated with Alzheimer's disease or dementia. This lack of
      association in the Yoruba might reflect genetic variation, environmental factors,
      as well as genetic/environmental interactions.

PMID- 16278855
TI  - COL6A1 genomic deletions in Bethlem myopathy and Ullrich muscular dystrophy.
AB  - We have identified highly similar heterozygous COL6A1 genomic deletions, spanning
      from intron 8 to exon 13 or intron 13, in two patients with Ullrich congenital
      muscular dystrophy and the milder Bethlem myopathy. The 5' breakpoints of both
      deletions are located within a minisatellite in intron 8. The mutations cause in
      frame deletions of 66 and 84 amino acids in the amino terminus of the triple
      helical domain, leading to intracellular accumulation of mutant polypeptides and
      reduced extracellular collagen VI microfibrils. Our studies identify a deletion
      prone region in COL6A1 and suggest that similar mutations can lead to congenital
      muscle disorders of different clinical severity.

PMID- 16278854
TI  - Clinical and biochemical spectrum of D-bifunctional protein deficiency.
AB  - OBJECTIVE: D-bifunctional protein deficiency is an autosomal recessive inborn
      error of peroxisomal fatty acid oxidation. Although case reports and small series
      of patients have been published, these do not give a complete and balanced
      picture of the clinical and biochemical spectrum associated with this disorder.
      METHODS: To improve early recognition, diagnosis, prognosis, and management of
      this disorder and to provide markers for life expectancy, we performed extensive
      biochemical studies in a large cohort of D-bifunctional protein-deficient
      patients and sent out questionnaires about clinical signs and symptoms to the
      responsible physicians. RESULTS: Virtually all children presented with neonatal
      hypotonia and seizures and died within the first 2 years of life without
      achieving any developmental milestones. However, within our cohort, 12 patients
      survived beyond the age of 2 years, and detailed information on 5 patients with
      prolonged survival (> or =7.5 years) is provided. INTERPRETATION: Biochemical
      analyses showed that there is a clear correlation between several biochemical
      parameters and survival of the patient, with C26:0 beta-oxidation activity in
      cultured skin fibroblasts being the best predictive marker for life expectancy.
      Remarkably, three patients were identified without biochemical abnormalities in
      plasma, stressing that D-bifunctional protein deficiency cannot be excluded when
      all peroxisomal parameters in plasma are normal.

PMID- 16278856
TI  - Rates of cerebral atrophy in autopsy-confirmed progressive supranuclear palsy.
AB  - OBJECTIVE: To determine the rates of cerebral atrophy and ventricular expansion
      in six patients with autopsy confirmed progressive supranuclear palsy (PSP) and
      multiple antemortem volumetric head MRI scans. METHODS: This study uses the
      boundary shift integral to determine rates of cerebral atrophy and ventricular
      expansion in six patients with pathologically confirmed PSP compared with six age
      and sex-matched control subjects. RESULTS: Patients with PSP had a rate of
      cerebral atrophy and ventricular expansion of 1.3 and 7.0% per year compared with
      0.4 and 1.8% in control subjects. INTERPRETATION: These rates provide a benchmark
      that can be used to monitor future treatment response in PSP.

PMID- 16278857
TI  - Strontium-containing hydroxyapatite (Sr-HA) bioactive cement for primary hip
      replacement: an in vivo study.
AB  - The purpose of this study was to evaluate the strontium-containing hydroxyapatite
      (Sr-HA) cement in primary hip replacement, using a rabbit model, and to
      investigate the histological findings at the cement-implant and bone-cement
      interfaces under weight-bearing conditions. Unilateral hip replacement was
      performed with Sr-HA cement or polymethylmethacrylate (PMMA) cement in rabbits
      and observations were made after 6 months. Good fixation between the Sr-HA cement
      and implant was observed. Osseointegration of the Sr-HA cement with cancellous
      bone was widespread. Many multinucleus cells covered the surface of the cement,
      and resorbed the superficial layer of the cement. By scanning electron microscopy
      (SEM) and energy-dispersive X-ray (EDX) analysis, high calcium and phosphorus
      levels were detected at the interface with a thickness of about 10 microm.
      Intimate contact was also observed between the Sr-HA cement and cortical bone
      without fibrous layer intervening. The overall affinity index of bone on Sr-HA
      cement was (85.06 +/- 5.40)%, which is significantly higher than that on PMMA
      cement (2.77%+/- 0.49%). On the contrary, a fibrous layer was consistently
      observed between PMMA cement and bone, and PMMA cement evoked an inflammatory
      response and foreign body reaction in the surrounding bony tissues. Results
      suggested good bioactivity and bone-bonding ability of the Sr-HA cement under
      weight-bearing conditions.

PMID- 16278858
TI  - Antioxidant inhibition of poly(carbonate urethane) in vivo biodegradation.
AB  - This study compared the effect of an antioxidant on the in vivo biodegradation of
      a poly(carbonate urethane) (PCU) and a poly(ether urethane) (PEU). Unstrained PEU
      and PCU films with and without Santowhite were implanted subcutaneously into 3
      month-old Sprague-Dawley rats for 3, 6, and 12 months. Characterization of
      unstabilized PEU and PCU with ATR-FTIR and SEM showed soft-segment and hard
      segment degradation consistent with previous studies. In particular, evidence of
      chain scission and crosslinking of the surface was present in the ATR-FTIR
      spectra of explanted specimens. Addition of 2.2 wt % antioxidant inhibited the in
      vivo degradation of both PCU and PEU. Although the antioxidant probably improved
      polyurethane biostability by decreasing the susceptibility of the polymer to
      degradation, modulation of the cellular response to prevent the release of
      degradative agents was also possible. To differentiate the effects, the foreign
      body response was investigated with the use of a standard cage implant protocol.
      Polyurethane films were implanted in wire mesh cages subcutaneously in rats for
      4, 7, and 21 days. There were no statistical differences among materials in the
      inflammatory exudate cell counts, adherent cell densities, or percent fusion of
      macrophages into foreign-body giant cells (FBGCs). Therefore, it was concluded
      that the antioxidant inhibited degradation by capturing oxygen radicals that
      would otherwise cause polyurethane chain scission and crosslinking.

PMID- 16278859
TI  - Study on blood compatibility with poly(2-methoxyethylacrylate)--relationship
      between surface structure, water structure, and platelet compatibility in 2
      methoxyethylacrylate/2-hydroxyethylmethacrylate diblock copolymer.
AB  - Diblock copolymers composed of 2-methoxyethylacrylate (MEA) and 2
      hydroxyethylmethacrylate (HEMA) were firstly prepared (the composition ratio =
      90/10, 79/21, 66/34, and 48/52 mol/mol) by anion living polymerization. ESCA
      analysis of their surface structures (dry state) revealed that PMEA segment was
      segregated to the top surface in all of the polymers, whereas the results of
      contact angle of water (wet state) showed that the surfaces were covered with
      PHEMA segment. In vitro platelet adhesion test showed that these polymers had the
      excellent compatibility with platelet compared to PHEMA homopolymer. Water
      structure in the hydrated copolymers was investigated by DSC and freezing bound
      water was observed for all the polymers like PMEA homopolymer, whereas it was not
      found in PHEMA homopolymer. Further investigation of water structure based on the
      results of DSC and EWCMS (equilibrium water content by moisture sorption)
      suggested that freezing bound water existed in PHEMA segment in addition to PMEA
      segment. We have proposed that the water plays a key role in the appearance of
      good blood compatibility of the copolymer, according to our previous works
      (Tanaka et al. Biomacromolecules 2002;3:36-41, Tanaka et al. J Biomed Mater Res A
      2004;68:684-695).

PMID- 16278860
TI  - In vivo biocompatibility of bacterial cellulose.
AB  - The biocompatibility of a scaffold for tissue engineered constructs is essential
      for the outcome. Bacterial cellulose (BC) consists of completely pure cellulose
      nanofibrils synthesized by Acetobacter xylinum. BC has high mechanical strength
      and can be shaped into three-dimensional structures. Cellulose-based materials
      induce negligible foreign body and inflammatory responses and are considered as
      biocompatible. The in vivo biocompatibility of BC has never been evaluated
      systematically. Thus, in the development of tissue engineered constructs with a
      BC scaffold, it is necessary to evaluate the in vivo biocompatibility. BC was
      implanted subcutaneously in rats for 1, 4, and 12 weeks. The implants were
      evaluated in aspects of chronic inflammation, foreign body responses, cell
      ingrowth, and angiogenesis, using histology, immunohistochemistry, and electron
      microscopy. There were no macroscopic signs of inflammation around the implants.
      There were no microscopic signs of inflammation either (i.e., a high number of
      small cells around the implants or the blood vessels). No fibrotic capsule or
      giant cells were present. Fibroblasts infiltrated BC, which was well integrated
      into the host tissue, and did not elicit any chronic inflammatory reactions. The
      biocompatibility of BC is good and the material has potential to be used as a
      scaffold in tissue engineering.

PMID- 16278861
TI  - Lipoprotein-associated phospholipase A2 is associated with risk of dementia.
AB  - OBJECTIVE: High levels of the inflammatory marker lipoprotein-associated
      phospholipase A2 (Lp-PLA2) have been proposed to be a predictor of coronary heart
      disease and stroke. Because both inflammation and vascular disease are associated
      with dementia, the objective of the present study was to examine the association
      between Lp-PLA2 and the risk of dementia. METHODS: Within the Rotterdam Study, a
      population-based prospective cohort study, we performed a case-cohort study. Of
      the 6,713 participants at risk for dementia, a random sample of 1,742 individuals
      was drawn. During follow-up (mean, 5.7 years), 302 incident dementia cases were
      identified. Cox proportional hazard models were used to estimate the association
      of Lp-PLA2 and dementia. RESULTS: We found that subjects with higher levels of Lp
      PLA2 had an increased risk of dementia. Compared with the first quartile of Lp
      PLA2, age- and sex-adjusted hazard ratios (HRs; 95% confidence interval [CI]) for
      dementia for the second, third, and fourth quartiles were 1.19 (0.78-1.81), 1.15
      (0.74-1.79), and 1.56 (1.03-2.37), respectively (p value for trend 0.04).
      Additional adjustment for cardiovascular and inflammatory factors did not change
      the estimates. INTERPRETATION: This is the first study to our knowledge that
      shows that Lp-PLA2 is associated with the risk of dementia independent of
      cardiovascular and inflammatory factors and provides evidence for a potential
      role of Lp-PLA2 in identifying subjects at risk for dementia.

PMID- 16278862
TI  - Ubiquilin 1 polymorphisms are not associated with late-onset Alzheimer's disease.
AB  - Several studies have reported evidence for linkage of late-onset Alzheimer's
      disease (LOAD) to chromosome 9. Recently, an intronic polymorphism affecting
      alternative splicing of exon 8 of ubiquilin 1 (UBQLN1) was reported to be
      associated with LOAD. We attempted to replicate this observation by genotyping
      this polymorphism, rs12344615 (also known as UBQ-8i), in a large sample of 1,544
      LOAD cases and 1,642 nondemented controls. We did not find any evidence that this
      single nucleotide polymorphism, or any of six others tested in UBQLN1, increases
      risk for LOAD.

PMID- 16278864
TI  - Interleukin-6 involvement in brain arteriovenous malformations.
AB  - We recently reported that the GG genotype of the interleukin-6 (IL-6)-174G>C
      promoter polymorphism is associated with clinical presentation of intracranial
      hemorrhage in brain arteriovenous malformation (AVM) patients. In this study, we
      investigated whether tissue IL-6 expression was associated with IL-6-174G>C
      genotype, and whether IL-6 was linked to downstream targets involved in
      angiogenesis and vascular instability. Our results showed that the highest IL-6
      protein levels in brain AVM tissue were associated with IL-6-174GG genotype (GG:
      57.7 +/- 20.2; GC: 35.6 +/- 26.6; CC: 13.9 +/- 10.2pg/mg; p = 0.001). IL-6
      protein levels were increased in AVM tissue from patients with hemorrhagic
      presentation compared with patients without hemorrhage (55 +/- 22 vs 40 +/-
      27pg/mg; p = 0.038). IL-6 messenger RNA expression strongly correlated with
      messenger RNA levels of IL-1beta, tumor necrosis factor-alpha, IL-8, matrix
      metalloproteinase-3 (MMP-3), MMP-9, and MMP-12. We further investigated the
      plausibility of IL-6 being an upstream cytokine responsible for initiating the
      angiogenic cascade by cell culture and animal experiments. IL-6 induced MMP-3 and
      MMP-9 expression and activity in mouse brain and increased proliferation and
      migration of cerebral endothelial cells. Together, our results suggest that the
      IL-6 genotype associated with intracranial hemorrhage modulates IL-6 expression
      in brain AVM tissue, which is consistent with the hypothesis that inflammatory
      processes induce angiogenic activity possibly contributory to brain AVM
      intracranial hemorrhage.

PMID- 16278866
TI  - Improvement in hydrophilicity of PHBV films by plasma treatment.
AB  - Poly(3-hydroxybutyrate-co-hydroxyvalerate) (PHBV) films were prepared by the
      solvent cast method. Oxygen and nitrogen plasma treatment were used to improve
      the hydrophilicity of the surface of PHBV films. The surface properties were
      characterized by contact angle measurement and X-ray photoelectron spectroscopy
      (XPS). The water contact angle of PHBV films decreased after plasma treatment,
      which suggested that the surfaces became more hydrophilic. The effects of
      exposure time, plasma generating power, and chamber pressure on water contact
      angle were investigated. Although the decrease of contact angle with both plasma
      treatments was similar, the change of PHBV surface structure was different. XPS
      analysis showed that the oxygen content and the ratio of O/C increased markedly
      after oxygen plasma treatment, while after nitrogen plasma treatment, the surface
      was enriched with nitrogen atoms. Furthermore, it was found that C-O and C-C
      bonds were broken with both plasma treatment, while different new bonds were
      formed, that is, COOH (for oxygen plasma), and C-N, C=N, and amide bonds (for
      nitrogen plasma) have been generated after plasma irradiation. Dog bone marrow
      stromal cell culture studies showed that cells grew better on the plasma treated
      surface. These results demonstrate potentiality of this method for grafting
      useful component in future tissue-engineering applications.

PMID- 16278867
TI  - Sub-micron texturing for reducing platelet adhesion to polyurethane biomaterials.
AB  - Platelet adhesion is a key event in thrombus development on blood-contacting
      medical devices. It has been demonstrated that changes to the chemistry of a
      material surface can reduce platelet adhesion. In this work, it is hypothesized
      that sub-micron surface textures may also reduce adhesion via a decrease in the
      surface area of material with which platelets can make contact, and hence a
      decreased probability of interaction with adhesive ligands. A polyether(urethane
      urea) was textured with two different sizes of sub-micron pillars using a
      replication molding technique that did not alter the material surface chemistry.
      Adhesion of platelets was assessed in a physiologically relevant shear stress
      range of 0-67 dyn/cm2 using a rotating disk system. Platelets were
      immunofluorescently labeled and adhesion was compared on smooth and textured
      samples. Platelet adhesion was greatest at low shear stress ranging from 0 to 5
      dyn/cm2, and sub-micron textures were observed to reduce platelet adhesion in
      this range. Additionally, non-adherent platelets did not demonstrate large-scale
      activation after exposure to textured samples. We conclude that surface textures
      with sub-platelet dimensions may reduce platelet adhesion from plasma to
      polyether(urethane urea) at low shear stress.

PMID- 16278868
TI  - Biological effects of calcium sulfate as a bone graft substitute in ovine
      metaphyseal defects.
AB  - Calcium sulfate has been used as a bone graft substitute in many fields, from
      dentistry to orthopedics. However, the results of many studies have yielded
      inconclusive results. In the present study, a sheep model was used with tibial
      and femoral metaphyseal defects to determine whether calcium sulfate was as
      effective as autograft and allograft in promoting new bone formation in a
      critical size defect. Medical-grade calcium sulfate pellets, autograft bone,
      allograft bone, or nothing was used to fill the metaphyseal defects. The sheep
      were allowed to heal for 12 weeks. Sagittal sections from the bones were analyzed
      with high-resolution contact radiographs, backscattered electron microscopy, and
      light microscopy. The volume fractions of bone within the defect perimeter were
      determined, and the histologic quality of the bone was observed. The volume
      fraction of new bone in the autograft, calcium sulfate, and allograft were not
      statistically different, but all were significantly different than the untreated
      control. The majority of the calcium sulfate had been resorbed at 12 weeks, and
      the histologic quality of the bone appeared similar to the autograft-treated
      bone. Calcium sulfate appears to be a useful biocompatible bone graft substitute
      that yields results similar to autograft bone in sheep metaphyseal defects.

PMID- 16278865
TI  - Cellular response to phase-separated blends of tyrosine-derived polycarbonates.
AB  - Two-dimensional thin films consisting of homopolymer and discrete compositional
      blends of tyrosine-derived polycarbonates were prepared and characterized in an
      effort to elucidate the nature of different cell responses that were measured in
      vitro. The structurally similar blends were found to phase separate after
      annealing with domain sizes dependent on the overall composition. The thin
      polymer films were characterized with the use of atomic force microscopy (AFM),
      water contact angles, and time-of-flight secondary ion mass spectrometry (TOF
      SIMS) and significant changes in roughness were measured following the annealing
      process. Genetic expression profiles of interleukin-1beta and fibronectin in
      MC3T3-E1 osteoblasts and RAW 264.7 murine macrophages were measured at several
      time points, demonstrating the time and composition-dependent nature of the cell
      responses. Real-time reverse transcriptase polymerase chain reaction (RT-PCR)
      depicted upregulation of the fibronectin gene copy numbers in each of the blends
      relative to the homopolymers. Moreover, the interleukin-1beta expression profile
      was found to be compositionally dependent. The data suggest strongly that optimal
      composition and processing conditions can significantly affect the acute
      inflammatory and extracellular matrix production responses.

PMID- 16278869
TI  - Testing the utility of rationally engineered recombinant collagen-like proteins
      for applications in tissue engineering.
AB  - Collagens are attractive proteins as materials for tissue engineering. Over the
      last decade, significant progress has been made in developing technologies for
      large-scale production of native-like human recombinant collagens. Yet, the
      rational design of customized collagen-like proteins for smart biomaterials to
      enhance the quality of engineered tissues has not been explored. We mapped the D4
      domain of human collagen II as most critical for supporting migration of
      chondrocytes and used this information to genetically engineer a collagen-like
      protein consisting of tandem repeats of the D4 domain (mD4 collagen). This novel
      collagen has been utilized to fabricate a scaffold for support of chondrocytes.
      We determined superior qualities of cartilaginous constructs created by
      chondrocytes cultured in scaffolds containing the mD4 collagen in comparison to
      those formed by chondrocytes cultured in bare scaffolds or those coated with wild
      type collagen II. Our results are a first attempt to rationally engineer collagen
      like proteins with characteristics tailored for specific needs of cartilage
      engineering and provide a basis for rational engineering of similar proteins for
      a variety of biomedical applications.

PMID- 16278870
TI  - Effect of cast molded rifampicin/silicone on Staphylococcus epidermidis biofilm
      formation.
AB  - Infection is one of the most common catheter-related complications, especially in
      shunt systems used to treat hydrocephalus. Staphylococcus epidermidis is directly
      related to biomaterial infections owing to its ability to form a biofilm on
      implanted materials. In this study, scanning electron microscopy (SEM) and atomic
      force microscopy (AFM) were employed to investigate the effect of the antibiotic
      rifampicin on the colonization and growth of S. epidermidis 35984 on the surface
      of silicone. A cast molding method was used to load rifampicin into the silicone
      precursor before it was cured. Bacteria with a diameter of 800-1000 nm and height
      of 200-500 nm were found to be embedded in the biofilm. Compact multilayer
      biofilm structures were found on silicone surfaces upon incubation for 4 and 24
      h. On the other hand, sparser biofilm structures were observed on rifampicin
      loaded surfaces after incubation for the same duration. Deformation of bacteria
      was observed by AFM. Moreover, different bacterial colony structures on the
      surfaces of silicone and rifampicin-loaded silicone were observed by AFM and SEM.

PMID- 16278871
TI  - Dissolution behavior and in vitro evaluation of sputtered hydroxyapatite films
      subject to a low temperature hydrothermal treatment.
AB  - Hydroxyapatite (HA) was coated onto titanium substrates using radio frequency
      sputtering. Some of the as-sputtered films were hydrothermally recrystallized at
      110 degrees C. In immersion tests, the as-sputtered film completely dissolved
      after 2 days in a culture medium, whereas the thickness of hydrothermally treated
      films increased with an increase in immersion period, reaching a thickness of
      127% after a period of 4 weeks. The proliferation and alkaline phosphatase (ALP)
      activity of MC3T3-E1 osteoblast-like cells on the as-sputtered and hydrothermally
      treated films were investigated, and the cell morphology was also observed using
      scanning electron microscopy. The proliferation of MC3T3-E1 cells on the as
      sputtered films was suppressed, whereas proliferation on the hydrothermally
      treated films was comparable to that on control and titanium substrate. The
      suppression of cell proliferation is associated with an increase in pH of the
      culture medium caused by dissolution of the as-sputtered film. After a 96-h
      culture time, the ALP activity of the cells on the hydrothermally treated film
      was higher than that on the control, titanium substrate, and as-sputtered film
      samples. From scanning electron microscopic observations, it was found that the
      MC3T3-E1 cells on the hydrothermally treated films were elongated and had
      established more intricate filopodia networks with each other, which were also
      observed for MC3T3-E1 cells on the as-sputtered films after a period of 24 h.

PMID- 16278872
TI  - How do brain tumors alter functional connectivity? A magnetoencephalography
      study.
AB  - OBJECTIVE: This study was undertaken to test the hypothesis that brain tumors
      interfere with normal brain function by disrupting functional connectivity of
      brain networks. METHODS: Functional connectivity was assessed by computing the
      synchronization likelihood in a broad band (0.5-60Hz) or in the gamma band (30
      60Hz) between all pairwise combinations of magnetoencephalography signals.
      Magnetoencephalography recordings were made at rest in 17 brain tumor patients
      and 15 healthy control subjects. For a given threshold of synchronization
      likelihood values, graphs of the suprathreshold connections between each
      magnetoencephalography channel and the others channels were built. RESULTS: In
      some regions, a variable number of channels without connectivity (missing
      connective points) at this threshold was found. The number of missing connective
      points was higher in patients with brain tumors than in control subjects (p <
      0.0001, broad and gamma band) and was higher for left-sided than right-sided
      tumors (p = 0.008, broad band; p < 0.0001, gamma band). Individual results
      analysis indicates that the majority of brain tumor patients display several
      regions with missing connective point alterations in the affected and in the
      contralateral hemisphere. INTERPRETATION: Our findings suggest that brain tumors
      induce a loss of functional connectivity that affects multiple brain regions, and
      that left side brain tumors have the more severe consequences in this respect.

PMID- 16278873
TI  - Electrolytic deposition of calcium phosphate/chitosan coating on titanium alloy:
      growth kinetics and influence of current density, acetic acid, and chitosan.
AB  - Electrolytically deposited calcium phosphate/chitosan coating demonstrated good
      bone marrow stromal cell attachment. The aim of this study was to understand the
      coating's growth kinetics as well as the effects of current density, acetic acid,
      and chitosan on the coating's formation. The scanning electron micrographs found
      that calcium phosphate crystals homogeneously distributed into chitosan
      aggregates as early as 30 min. X-ray diffraction patterns and Fourier transform
      infrared spectra demonstrated that the coating experienced a compositional
      conversion from octacalcium phosphate to carbonate apatite during the deposition
      process. Electric current influenced the deposition. Higher current density
      accelerated the process and induced faster and more chitosan deposition. Both
      acetic acid and chitosan were found to inhibit calcium phosphate deposition.
      Chitosan was thought to induce stronger effects than acetic acid did.
      Furthermore, the inhibitive effect related to their concentration in the
      electrolyte. When chitosan concentration increased to a certain degree, this
      inhibitive effect not only affected calcium phosphate deposition, but also
      affected its own deposition. The chitosan content within the hybrid coating was
      small, which could be verified through Raman spectrum. At the same time, no clear
      evidence of chemical reactions could be found between these two components. We
      considered that both components were just naturally wrapped to form as a whole.

PMID- 16278874
TI  - Characterization and bioactivity of tape-cast and sintered TCP sheets.
AB  - The purpose of this study was to investigate the influence of sintering
      temperature on in vivo and in vitro bioactivities of sintered tricalcium
      phosphate (TCP) sheets prepared by the tape casting technique. Green sheets of
      beta-TCP prepared by tape casting were sintered for 2 h in a furnace at
      atmospheric pressure, at five different sintering temperatures: 900, 1000, 1100,
      1150, and 1200 degrees C. Measurement of X-ray diffraction and Fourier transform
      infrared spectrometry showed the presence of alpha-tricalcium phosphate phase in
      the TCP sheet sintered at 1200 degrees C, in addition to beta-TCP phase. As
      compared with the other sintered TCP sheet, the TCP sheet sintered at 1200
      degrees C demonstrated a lower dissolution rate in phosphate buffered saline
      solution at 37 degrees C and pH 7.4 over 24 weeks, and more amount of apatite
      formation in Hanks' balanced salt solution with pH 7.4 was observed. After 4
      weeks' implantation of sintered TCP sheets into tibial diaphyses of rabbits, the
      bone-sheet contact of the TCP sheet sintered at 1200 degrees C was significantly
      higher than that of the TCP sheet sintered at 900 degrees C. These results
      indicate that a flat sintered TCP sheet prepared by tape casting is a promising
      material for a bone substitute.

PMID- 16278875
TI  - Tissue engineered cartilage using human articular chondrocytes immortalized by
      HPV-16 E6 and E7 genes.
AB  - Chondrocytes are useful as a cell culture system for studying arthritic
      degeneration in tissue engineered cartilage. However, primary chondrocytes have
      short in vitro lifespan and rapid shift of collagen phenotype. In this study, we
      used a high dosage of retroviral vector LXSN16E6E7 to transduce human primary
      chondrocytes and obtained an actively proliferating cell line, designated hPi,
      which expresses HPV-16 E6/E7 mRNA in early passages. Parental primary
      chondrocytes cease to grow after five passages, whereas hPi could be propagated
      beyond 100 passages without requiring additional cell elements in defined medium.
      After 48 passages, hPi can also give many profiles similar to those of parental
      primary chondrocyte, including type II collagen in mRNA and protein level,
      aggrecan in mRNA level, lacunae in type I collagen matrices, and morphology with
      GAG-specific Alcian blue staining. hPi has shown neoplastic transformation, as
      examined by NOD-SCID mice tumorigenicity assays for 3 months. Our results
      indicated that human primary chondrocytes could be immortalized by transduction
      with HPV-16 E6/E7, preserving stable cartilage-specific differentiation markers.
      The established chondrocyte cell line could provide a novel model to engineer
      cartilage in vitro and in vivo for cartilage repair research and clinical
      application.

PMID- 16278876
TI  - Osteoblast response to zirconia-hybridized pyrophosphate-stabilized amorphous
      calcium phosphate.
AB  - Calcium phosphate bioceramics, such as hydroxyapatite, have long been used as
      bone substitutes because of their proven biocompatibility and bone binding
      properties in vivo. Recently, a zirconia-hybridized pyrophosphate-stabilized
      amorphous calcium phosphate (Zr-ACP) has been synthesized, which is more soluble
      than hydroxyapatite and allows for controlled release of calcium and phosphate
      ions. These ions have been postulated to increase osteoblast differentiation and
      mineralization in vitro. The focus of this work is to elucidate the
      physicochemical properties of Zr-ACP and to measure cell response to Zr-ACP in
      vitro using a MC3T3-E1 mouse calvarial-derived osteoprogenitor cell line. Cells
      were cultured in osteogenic medium and mineral was added to culture at different
      stages in cell maturation. Culture in the presence of Zr-ACP showed significant
      increases in cell proliferation, alkaline phosphatase activity (ALP), and
      osteopontin (OPN) synthesis, whereas collagen synthesis was unaffected. In
      addition, calcium and phosphate ion concentrations and medium pH were found to
      transiently increase with the addition of Zr-ACP, and are hypothesized to be
      responsible for the osteogenic effect of Zr-ACP.

PMID- 16278877
TI  - Phase II jaw movements and masseter muscle activity during chewing in Papio
      anubis.
AB  - It was proposed that the power stroke in primates has two distinct periods of
      occlusal contact, each with a characteristic motion of the mandibular molars
      relative to the maxillary molars. The two movements are called phase I and phase
      II, and they occur sequentially in that order (Kay and Hiiemae [1974] Am J. Phys.
      Anthropol. 40:227-256, Kay and Hiiemae [1974] Prosimian Biology, Pittsburgh:
      University of Pittsburgh Press, p. 501-530). Phase I movement is said to be
      associated with shearing along a series of crests, producing planar phase I
      facets and crushing on surfaces on the basins of the molars. Phase I terminates
      in centric occlusion. Phase II movement is said to be associated with grinding
      along the same surfaces that were used for crushing at the termination of phase
      I. Hylander et al. ([1987] Am J. Phys. Anthropol. 72:287-312; see also Hiiemae
      [1984] Food Acquisition and Processing, London: Academic Press, p. 257-281;
      Hylander and Crompton [1980] Am J. Phys. Anthropol. 52:239-251, [1986] Arch.
      Oral. Biol. 31:841-848) analyzed data on macaques and suggested that phase II
      movement may not be nearly as significant for food breakdown as phase I movement
      simply because, based on the magnitude of mandibular bone strain patterns,
      adductor muscle and occlusal forces are likely negligible during movement out of
      centric occlusion. Our goal is to better understand the functional significance
      of phase II movement within the broader context of masticatory kinematics during
      the power stroke. We analyze vertical and transverse mandibular motion and
      relative activity of the masseter and temporalis muscles during phase I and II
      movements in Papio anubis. We test whether significant muscle activity and, by
      inference, occlusal force occurs during phase II movement. We find that during
      phase II movement, there is negligible force developed in the superficial and
      deep masseter and the anterior and posterior temporalis muscles. Furthermore,
      mandibular movements are small during phase II compared to phase I. These results
      suggest that grinding during phase II movement is of minimal importance for food
      breakdown, and that most food breakdown on phase II facets occurs primarily at
      the end of phase I movement (i.e., crushing during phase I movement). We note,
      however, that depending on the orientation of phase I facets, significant
      grinding also occurs along phase I facets during phase I.

PMID- 16278878
TI  - Vertebrate homologues of Frodo are dynamically expressed during embryonic
      development in tissues undergoing extensive morphogenetic movements.
AB  - Frodo has been identified as a protein interacting with Dishevelled, an essential
      mediator of the Wnt signaling pathway, critical for the determination of cell
      fate and polarity in embryonic development. In this study, we use specific gene
      probes to characterize stage- and tissue-specific expression patterns of the
      mouse Frodo homologue and compare them with Frodo expression patterns in Xenopus
      embryos. In situ hybridization analysis of mouse Frodo transcripts demonstrates
      that, similar to Xenopus Frodo, mouse Frodo is expressed in primitive streak
      mesoderm, neuroectoderm, neural crest, presomitic mesoderm, and somites. In many
      cases, Frodo expression is confined to tissues undergoing extensive
      morphogenesis, suggesting that Frodo may be involved in the regulation of cell
      shape and motility. Highly conserved dynamic expression patterns of Frodo
      homologues indicate a similar function for these proteins in different
      vertebrates.

PMID- 16278879
TI  - Molecular genetics in classic Ehlers-Danlos syndrome.
AB  - Classic Ehlers-Danlos syndrome is a heritable disorder of connective tissue that
      is characterized by skin hyperextensibility, fragile and soft skin, delayed wound
      healing with formation of atrophic scars, easy bruising, and generalized joint
      hypermobility. Mutations in the COL5A1 and the COL5A2 gene, encoding the alpha1
      and the alpha2-chain of type V collagen respectively, are identified in
      approximately 50% of patients with a clinical diagnosis of classic EDS. In
      approximately one third of patients, the disease is caused by a mutation leading
      to a non-functional COL5A1 allele, and resulting in haplo-insufficiency of type V
      collagen. In a smaller proportion of patients, a structural mutation in COL5A1 or
      COL5A2, resulting in the production of a functionally defective type V collagen
      protein, is responsible for the phenotype. Inter- and intrafamilial phenotypic
      variability is observed, but no genotype-phenotype correlations can be made so
      far. The relatively low mutation detection rate in the COL5A1/A2 genes suggests
      genetic heterogeneity. Indeed rarely mutations in type I collagen have been
      identified in patients with classic EDS. Mutations in the gene for tenascin-X
      have been implicated in an autosomal recessive condition phenotypically
      overlapping with classic EDS. Several other candidate genes, such as decorin,
      have emerged from the study of transgenic mouse models with clinical and
      ultrastructural features reminiscent of classic EDS. However, to date, no human
      examples have been reported for these mouse models.

PMID- 16278880
TI  - Tenascin-X, collagen, elastin, and the Ehlers-Danlos syndrome.
AB  - Tenascin-X is an extracellular matrix protein initially identified because the
      gene encoding it overlaps with the human CYP21B gene. Because studies of gene and
      protein function of other tenascins had been poorly predictive of essential
      functions in vivo, we used a genetic approach that critically relied on an
      understanding of the genomic locus to uncover an association between inactivating
      tenascin-X mutations and novel recessive and dominant forms of Ehlers-Danlos
      syndrome (EDS). Tenascin-X provides the first example of a gene outside of the
      fibrillar collagens and their processing enzymes that causes EDS. Tenascin-X null
      mice recapitulate the skin findings of the human disease, confirming a causative
      role for this gene in EDS. Further evaluation of these mice showed that tenascin
      X is an important regulator of collagen deposition in vivo, suggesting a novel
      mechanism of disease in this form of EDS. Further studies suggest that tenascin-X
      may do this through both direct and indirect interactions with the collagen
      fibril. Recent studies show that TNX effects on matrix extend beyond the collagen
      to the elastogenic pathway and matrix remodeling enzymes. Tenascin-X serves as a
      compelling example of how human "experiments of nature" can guide us to an
      understanding of genes whose function may not be evident from their sequence or
      in vitro studies of their encoded proteins.

PMID- 16278881
TI  - Osteogenesis imperfecta, current and future medical treatment.
AB  - Physiotherapy, rehabilitation, and orthopedic surgery are the mainstay of
      treatment in moderate to severe forms of osteogenesis imperfecta (OI).
      Nevertheless, medical treatment with bisphosphonates can bring significant
      additional improvements. Benefits include decreased pain, lower fracture
      incidence, and better mobility. Among the various bisphosphonates, intravenous
      pamidronate has been studied in most detail. It is unclear whether oral
      bisphosphonates are as effective as intravenous pamidronate. As the effect of
      bisphosphonates on the skeleton is largest during growth, it appears logical to
      start medical therapy of OI patients as early as possible. However, the optimal
      treatment regimen and the long-term consequences of pamidronate treatment in
      children are currently unknown. Given these uncertainties, treatment with
      bisphosphonates during growth should be reserved for patients who have
      significant clinical problems, such as vertebral compression fractures or long
      bone deformities. Medical therapies other than bisphosphonates, such as growth
      hormone and parathyroid hormone, play a minor role at present. Gene-based therapy
      currently remains in the early stages of preclinical research.

PMID- 16278882
TI  - Molecular characterization of the Caenorhabditis elegans ALP/Enigma gene alp-1.
AB  - Members of the ALP/Enigma family of PDZ-LIM proteins play a role in cytoskeletal
      anchorage and mutations in at least one member of this family are associated with
      human cardiomyopathy. Here, we describe the analysis of the Caenorhabditis
      elegans alp-1 gene. alp-1 is predicted to encode the entire nematode ALP/Enigma
      protein family, consisting of one ALP-related protein with a single LIM domain
      and three Enigma-like proteins containing four LIM domains. We demonstrate that
      the ALP-1 proteins are expressed in muscle cells, where they localize to actin
      anchorage and muscle attachment sites. We show that the PDZ domain of the ALP-1
      proteins is sufficient to target the protein to the dense bodies, which are
      important actin anchorage sites in C. elegans body wall muscle. We demonstrate
      that the C. elegans ALP/Enigma proteins are also localized to cell-cell junctions
      and to both epithelial and muscle cell nuclei. These findings suggest new roles
      for the ALP/Enigma protein family that may lead to the understanding of their
      involvement in cardiomyopathy.

PMID- 16278884
TI  - Unusual cerebrotendinous xanthomatosis with fronto-temporal dementia phenotype.
AB  - Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage
      disease caused by a deficiency of the mitochondrial enzyme 27-sterol hydroxylase
      (CYP27). We report a 53-year-old man, with an unusual phenotype of CTX. He had
      xanthomas since adolescence. He had no mental retardation and developed at 44
      years a progressive neuropsychiatric phenotype, suggestive of fronto-temporal
      dementia according to clinical Neary criteria. Cataract and ataxia were absent.
      Cerebral MRI revealed diffuse hyperintense T2 abnormalities in the supratentorial
      white matter without cerebellar atrophy or lesions, while Technetium-99m-ECD
      brain SPECT revealed a severe cerebellar hypoperfusion. Serum cholestanol level
      was elevated with excessive urinary bile alcohols excretion. Mutation analysis
      revealed that he was compound heterozygous for two mutations in the CYP27A1 gene:
      1016 C > T (exon 5) on one allele and a novel mutation, 1435C > G (exon 8) on the
      other allele. A follow-up study was conducted to evaluate the effects of
      chenodeoxycholic acid (CDCA) and simvastatin treatment during 3 years. In spite
      of this treatment, cognitive functions declined but no other signs of
      neurological deterioration appeared.

PMID- 16278883
TI  - A genetic approach to fracture epidemiology in childhood.
AB  - The purpose of this report is to provide a review of both childhood fracture
      epidemiology and known heritable causes for fracture predisposition to the
      Medical Geneticist, who is frequently consulted to assess children with multiple
      or unexplained fractures for a physiologic etiology. A detailed knowledge of the
      clinical and laboratory evaluation for osteogenesis imperfecta (OI) and other
      single-gene disorders is obviously essential to complete a useful evaluation of
      such children. The experienced clinician will immediately recognize that single
      gene disorders represent only a small fraction of these patients. In infants, non
      accidental trauma (NAT) unfortunately is the likely explanation for the fracture
      pattern, but in some infants, and certainly in older children with recurrent
      fractures, no medical explanations can be found. Recent studies in which bone
      mineral density (BMD) has been associated with genetic variation at a number of
      candidate genes are promising but these studies are too premature yet to be used
      clinically. Nonetheless, we do expect that in the future whole-genome approaches
      in conjunction with key clinical and epidemiological variables may be combined
      through an informatics approach to create better predictors of fracture
      susceptibility for these populations of patients.

PMID- 16278885
TI  - Iridic and retinal coloboma associated with prenatal methimazole exposure.

PMID- 16278886
TI  - Ebstein anomaly and duplication of the distal arm of chromosome 15: report of two
      patients.
AB  - Ebstein anomaly of the tricuspid valve is an uncommon congenital heart defect. We
      report two unrelated patients with Ebstein anomaly and duplication of the distal
      long arm of chromosome 15 (15q22 --> qter and 15q24 --> qter). Duplication of 15q
      is a well-described phenotype that includes congenital heart defects, and these
      are the first cases with Ebstein anomaly. Duplication of 15q likely affects the
      early morphogenesis of cardiac structures, including the normal formation of the
      tricuspid valve.

PMID- 16278887
TI  - Fetal type IV glycogen storage disease: clinical, enzymatic, and genetic data of
      a pure muscular form with variable and early antenatal manifestations in the same
      family.
AB  - We report on a family of three consecutive fetuses affected by type IV glycogen
      storage disease (GSD IV). In all cases, cervical cystic hygroma was observed on
      the 12-week-ultrasound examination. During the second trimester, fetal hydrops
      developed in the first pregnancy whereas fetal akinesia appeared in the second
      pregnancy. The diagnosis was suggested by microscopic examination of fetal
      tissues showing characteristic inclusions exclusively in striated fibers, then
      confirmed by enzymatic studies on frozen muscle. Antenatal diagnosis was
      performed on the third and fourth pregnancies: cervical cystic hygroma and low
      glycogen branching enzyme (GBE) activity on chorionic villi sample (CVS) were
      detected in the third pregnancy whereas ultrasound findings were normal and GBE
      activity within normal range on CVS in the fourth pregnancy. Molecular analysis
      showed that the mother was heterozygous for a c.1471G > C mutation in exon 12,
      leading to the replacement of an alanine by a tyrosine at codon 491 (p.A491T);
      the father was heterozygous for a c.895G > T mutation in exon 7, leading to the
      creation of a stop codon at position 299 (p.G299X). GSD IV has to be considered
      in a context of cervical cystic hygroma with normal karyotype, particularly when
      second trimester hydrops or akinesia develop. Enzymatic analysis of GBE must be
      performed on CVS or amniotic cells to confirm the diagnosis. Characteristic
      intracellular inclusions are specific to the disease and should be recognized,
      even in macerated tissues after fetal death. Genetic analysis of the GBE gene may
      help to shed some light on the puzzling diversity of GSD IV phenotypes.

PMID- 16278888
TI  - Molecular cytogenetic characterization of a familial
      der(1)del(1)(p36.33)dup(1)(p36.33p36.22) with variable phenotype.
AB  - Chromosome deletions involving 1p36 are the most common known terminal
      rearrangements occurring at a frequency of approximately 1 in 5,000 live births.
      In contrast, duplications of the same region have been reported rarely. We
      describe a familial rearrangement der(1)del(1)(p36.33)dup(1)(p36.33p36.22)
      identified in a mother, daughter, and son. These individuals help define a
      syndrome with variable mental disability, attention deficit-hyperactivity
      disorder, and a distinctive facial appearance with wide palpebral fissures, broad
      nasal root, macrostomia, ear malformations, and prominent incisors. Based on our
      results we suggest that the complex rearrangement seen in our family could be the
      result of the breakage-fusion-bridge (BFB) cycles model of formation.

PMID- 16278890
TI  - The pattern of MyoD and contractile protein localization in primary epaxial
      myotome reflects the dynamic progression of nascent myoblast differentiation.
AB  - The localization of contractile and regulatory proteins in early stages of
      epaxial primary myotome development was analyzed by immunofluorescence
      microscopy. Contractile proteins that appear in an ordered sequence in the rostro
      caudal axis of somite development were found to reiterate that sequence in the
      dorso-medial-to-ventro-lateral axis of primary epaxial myotome development. Pair
      wise localization of MyoD-titin, desmin-titin, and desmin-myosin defined three
      zones extending from the dermomyotome dorso-medial lip (DML) into the primary
      myotome layer. Zones M1 and M2, which were positive for MyoD + titin and MyoD +
      titin + desmin, respectively, were restricted to the dorso-medial-most extremity
      of the myotome layer and did not expand during the course of myotome development.
      Zone M3 was positive for MyoD, desmin, titin, myosin, and cardiac troponin T and
      was the only zone that expanded during primary myotome development. Myotome
      fibers in zone M3 were unit-length, spanning the full rostro-caudal axis of the
      myotome while fibers in zones M1 and M2 were shorter than unit length. Anti-myoD
      immunofluorescence, when detected in cells lacking contractile-protein-positive
      cytoplasm, was restricted to the DML and nascent myotome cells immediately
      subjacent to the DML. These results demonstrate a dynamic spatio-temporal
      sequence in the differentiation program of nascent myotome cells as they emerge
      from the DML; zones M1 and M2 reflect standing waves of sequential contractile
      protein activation during the maturation of nascent myotomal myoblasts, while the
      expanding zone M3 reflects the accumulation of mature myotome fibers expressing a
      full cohort contractile proteins.

PMID- 16278889
TI  - Genomic profiling of mixer and Sox17beta targets during Xenopus endoderm
      development.
AB  - The transcription factors Mixer and Sox17beta have well-characterized roles in
      endoderm specification during Xenopus embryogenesis. In order to more thoroughly
      understand the mechanisms by which these endodermal regulators act, we expressed
      Mixer and Sox17beta in naive ectodermal tissue and, using oligonucleotide-based
      microarrays, compared their genomic transcriptional profile to that of unaffected
      tissue. Using this approach, we identified 71 transcripts that are upregulated by
      Mixer or Sox17beta, 63 of which have previously uncharacterized roles in endoderm
      development. Furthermore, an in situ hybridization screen using antisense probes
      for several of these clones identified six targets of Mixer and/or Sox17beta that
      are expressed in the endoderm during gastrula stages, providing new and regional
      markers of the endoderm. Our results contribute further insight into the
      functions of Mixer and Sox17beta and bring us closer to understanding at the
      molecular level the pathways that regulate endoderm development.

PMID- 16278891
TI  - A family with Duane anomaly and distal limb abnormalities: a further family with
      the arthrogryposis-ophthalmoplegia syndrome.
AB  - A two-generation family is reported in which three members have Duane anomaly and
      distal limb abnormalities. All three affected have photopic electroretinogram
      responses that are abnormal or at the lower limit of the normal range with normal
      scotopic responses. Two affected family members also have hearing loss. The
      likeliest diagnosis is the syndrome listed as "arthrogryposis-ophthalmoplegia
      syndrome" on the London Dysmorphology Database or as "arthrogryposis with
      oculomotor limitation and electroretinal abnormalities" or "oculomelic aplasia"
      in OMIM [MIM 108145]. In view of the similarities with Okihiro syndrome, a search
      for mutations within the SALL4 gene was undertaken, but none were identified.

PMID- 16278892
TI  - Myhre syndrome in a female with previously undescribed symptoms: further
      delineation of the phenotype.
AB  - Myhre syndrome is a rare connective tissue disease characterized by
      nonprogressive stiffness of the large joints, short stature with a peculiar
      build, and a distinctive facial phenotype. Developmental delay is common. Three
      female patients have so far been described. Here, we report on a 16-year-old
      female with Myhre syndrome. She has vertebral defects, hypertrophic scar
      formation, and a stiff skin in addition to the features that have previously been
      reported in association with Myhre syndrome.

PMID- 16278893
TI  - Perlman syndrome: clinical report and nine-year follow-up.
AB  - We present the clinical and follow-up data of a female infant with Perlman
      syndrome from birth to the age of 9 years. Main features of Perlman syndrome
      include polyhydramnios, fetal overgrowth, neonatal macrosomia, macrocephaly,
      dysmorphic facial features, visceromegaly, nephroblastomatosis, and a
      predisposition for Wilm's tumor. In our patient, the nephromegaly with
      nephroblastomatosis was not present at birth or during the neonatal period; it
      became evident in the first months of postnatal life. A Wilm's tumor was
      diagnosed when she was about 1 year old. Long term follow-up documents the
      natural history of Perlman syndrome and allows us to establish the long-term
      prognosis of the affected individuals.

PMID- 16278894
TI  - Distal arthrogryposis type 2A may be associated with juvenile glaucoma.

PMID- 16278895
TI  - RE: An epidemiological analysis of CHARGE syndrome: preliminary results from a
      Canadian study [Issekutz et al., 2005].

PMID- 16278896
TI  - A paternally derived inverted duplication of distal 14q with a terminal 14q
      deletion.
AB  - A girl presented with a phenotype including neonatal hypotonia, psychomotor
      retardation, mental retardation, short stature, and facial dysmorphism. She
      demonstrated common features of both 14q31-qter duplication and terminal 14q
      deletion. She had undergone surgery for patent ductus arteriosus and pyloric
      stenosis in infancy. Her karyotype was 46,XX,der(14) dup(14)(q32.3
      q31.3)del(14)(q32.3). Molecular cytogenetic analysis showed a paternally derived
      14q31.3-q32.3 duplication and a terminal 14q deletion and led to the correlations
      between a particular genotype and phenotype. This is the first description of a
      deletion and inverted duplication of 14q, and adds 14q to the growing list of the
      inverted duplication associated with a terminal deletion.

PMID- 16278897
TI  - Report of a third family with Oliver syndrome.

PMID- 16278898
TI  - Severe bilateral panlobular emphysema and pulmonary arterial hypoplasia: unusual
      manifestations of Menkes disease.
AB  - Menkes disease is an X-linked recessive disorder of copper transport
      characterized by neurological deterioration, connective tissue, and vascular
      defects, abnormal hair, and death in early childhood. We report on a patient with
      Menkes disease in whom severe diffuse emphysema caused respiratory failure and
      death at 14 months of age. He had severe growth and developmental delays and
      other typical clinical manifestations of Menkes disease. He developed respiratory
      problems requiring continuous supplemental oxygen and a progressively enlarging
      soft tissue mass appeared on the neck. Imaging studies revealed cystic spaces in
      multiple lobes of the lung consistent with bullous emphysema. The neck mass was
      determined to be an internal jugular venous aneurysm. At autopsy, extensive
      emphysematous change was evident. Post-mortem barium injections of the pulmonary
      arterial system revealed marked dilatation and tortuosity of the preacinar
      pulmonary arteries and reduced numbers of intra-acinar arteries. Severe
      emphysema, presumably caused by abnormal elastin due to deficiency of the copper
      dependent enzyme lysyl oxidase, may represent an underestimated clinical
      complication of Menkes disease and should be considered in the differential
      diagnosis of chronic respiratory disease in these patients.

PMID- 16278899
TI  - Co-existing point mutations of mitochondrial DNA in a patient with a heart
      abnormality and Pearson syndrome-like symptoms.

PMID- 16278900
TI  - Wilms tumor in an 11-year-old with hemihyperplasia.

PMID- 16278901
TI  - Mos 46,XX,r(18).ish r(18)(18ptel-,18qtel-)/46,XX.ish del(18)(18ptel-): an example
      for successive ring chromosome formation.

PMID- 16278902
TI  - Majewski osteodysplastic primordial dwarfism type II (MOPD II) complicated by
      stroke: clinical report and review of cerebral vascular anomalies.
AB  - We report on a 2 9/12-year-old boy with disproportionate short stature,
      microcephaly, subtle craniofacial dysmorphisms, and generalized skeletal
      dysplasia, who developed a left hemiparesis. Brain neuroimaging disclosed a
      complex cerebral vascular anomaly (CVA) with stenosis of the right anterior
      cerebral artery and telangiectatic collateral vessels supplying the cerebral
      cortex, consistent with moyamoya disease. Based on clinical and skeletal
      features, a diagnosis of Majewski osteodysplastic primordial dwarfism type II
      (MOPD II) was established. Review of 16 published patients with CVA affected by
      either Seckel syndrome or MOPD II suggested that CVA is preferentially associated
      to the latter subtype affecting about 1/4 of the patients.

PMID- 16278904
TI  - CRELD1 and GATA4 gene analysis in patients with nonsyndromic atrioventricular
      canal defects.

PMID- 16278903
TI  - A patient with monosomy 1p36, atypical features and phenotypic similarities with
      Cantu syndrome.
AB  - We report on a 16-year-old boy with a distal 1p36 deletion with some clinical
      features consistent with Cantu syndrome (OMIM#239850). He also has
      hypercholesterolemia, type II diabetes, recurrent bony fractures, and non
      alcoholic steatohepatitis, not previously described in either condition. The 1p36
      deletion was detected in a screen of all chromosome subtelomeres using multiplex
      ligation-dependent probe amplification and was verified using FISH with a region
      specific BAC clone. We suggest that patients suspected of having Cantu syndrome,
      especially those with unusual or more severe manifestations be analyzed for
      distal 1p36 deletions.

PMID- 16278905
TI  - Investigation of patients with mental retardation and dysmorphic features using
      comparative genomic hybridization and subtelomeric multiplex ligation dependent
      probe amplification.

PMID- 16278907
TI  - Costello syndrome and hyperinsulinemic hypoglycemia.
AB  - Costello syndrome is characterized by mental retardation, loose skin, coarse
      facies, skeletal abnormalities, cardiovascular abnormalities (congenital heart
      defects, cardiomyopathy, rhythm disturbances), and predisposition to neoplasia.
      Endocrine abnormalities including growth hormone deficiency, adrenal
      insufficiency, glucose intolerance, parathyroid adenoma with hyperprolactinemia
      and hypoglycemia have been described. Hypoglycemia has been documented due to
      growth hormone and cortisol deficiency. We report on two patients with Costello
      syndrome and persistent hyperinsulinemic hypoglycemia and review the endocrine
      manifestations of Costello syndrome. Both patients required diazoxide therapy to
      stop the unregulated insulin secretion and maintain normoglycemia. The mechanism
      of persistent hyperinsulinism in patients with Costello syndrome is unclear.

PMID- 16278908
TI  - No detectable genomic aberrations by BAC array CGH in Kabuki make-up syndrome
      patients.

PMID- 16278909
TI  - A multilayer poly(dimethylsiloxane) electrospray ionization emitter for sample
      injection and online mass spectrometric detection.
AB  - An ESI emitter made of poly(dimethylsiloxane) interfaces on-chip sample
      preparation with MS detection. The unique multilayer design allows both the
      analyte and the spray solutions to reside on the device simultaneously in
      discrete microfluidic environments that are spatially separated by a
      polycarbonate track-etched, nanocapillary array membrane (NCAM). In direct spray
      mode, voltage is applied to the microchannel containing a spray solution
      delivered via a syringe pump. For injection, the spray potential is lowered and a
      voltage is applied that forward biases the membrane and permits the analyte to
      enter the spray channel. Once the injection is complete, the bias potential is
      switched off, and the spray voltage is increased to generate the ESI of the
      injected analyte plug. Consecutive injections of a 10 microM bovine insulin
      solution are reproducible and produce sample plugs with limited band broadening
      and high quality mass spectra. Peptide signals are observed following transport
      through the NCAM, even when the peptide is dissolved in solutions containing up
      to 20% seawater. The multilayer emitter shows great potential for performing
      multidimensional chemical manipulations on-chip, followed by direct ESI with
      negligible dead volume for online MS analysis.

PMID- 16278911
TI  - Enantiospecific chemisorption of small molecules on intrinsically chiral Cu
      surfaces.

PMID- 16278912
TI  - Staggered to eclipsed conformational rearrangement of [Co2(CO)6(PPh3)2] in the
      solid state: an X-ray diffraction study at high pressure and low temperature.

PMID- 16278910
TI  - Fabrication and performance of a three-dimensionally adjustable device for the
      amperometric detection of microchip capillary electrophoresis.
AB  - A microchip CE-amperometric detection (AD) system has been fabricated by
      integrating a two-dimensionally adjustable CE microchip and an AD cell containing
      a one-dimensionally adjustable disk detection electrode in a Plexiglas holder. It
      facilitates the precise 3-D alignment between the channel outlet and the
      detection electrode without a complicated 3-D manipulator. The performance of
      this unique system was demonstrated by separating five aromatic amines (1,4
      phenyldiamine, aniline, 2-methylaniline, 4-chloroaniline, and 1-naphthylamine) of
      environmental concern. Factors influencing their separation and detection
      processes were examined and optimized. The five analytes have been well separated
      within 140 s in a 74 cm long separation channel at a separation voltage of +2500
      V using a 10 mM phosphate buffer (pH 3.5). Highly linear response is obtained for
      the five analytes over the range 20-200 microM with the detection limits ranging
      from 0.46 to 1.44 microM, respectively. The present system demonstrated long-term
      stability and reproducibility with RSDs of less than 5% for the peak current (n =
      9). The new approach for the microchannel-electrode alignment should find a wide
      range of applications in CE, flowing injection analysis, and other microfluidic
      analysis systems.

PMID- 16278914
TI  - Tl2[Aryl2P4]: a thallium complexed diaryltetraphosphabutadienediide and its two
      electron oxidation to a diaryltetraphosphabicyclobutane, aryl2p4.

PMID- 16278913
TI  - Photochemical regulation of DNA-binding specificity of MyoD.

PMID- 16278915
TI  - On the rigidity of polynorbornenes with dipolar pendant groups.
AB  - A range of polynorbornenes (PNBs) with fused dipolar pendant groups at C-5,6
      positions was synthesized by ring-opening metathesis polymerization catalyzed by
      a ruthenium carbene complex (Grubbs I). Photophysical studies, EFISH
      measurements, and atomic force microscopy images have been used to investigate
      the structures and morphology of these polymers. These results suggest that the
      polymers may adopt rigid rod-like structures. The presence of the double bonds in
      PNBs appeared to be indispensable for the rigidity of the polymers. Interaction
      between unsaturated pendant groups may result in coherent alignment leading to a
      rod-like structure.

PMID- 16278916
TI  - A mechanistic and kinetic study of the formation of metal nanoparticles by using
      synthetic tyrosine-based oligopeptides.
AB  - Synthetic oligopeptides containing redox-active tyrosine residues have been
      employed to prepare gold and silver nanoparticles. In this reduction process an
      electron from the tyrosinate ion of the peptide is transferred to the metal ion
      at basic pH through the formation of a tyrosyl radical, which is eventually
      converted to its dityrosine form during the reaction. This reaction mechanism was
      confirmed from UV-visible, fluorescence, and EPR spectroscopy and was found to be
      pH-dependent. Transmission electron microscopy measurement shows that the average
      size and the monodispersity of gold nanoparticles increase as the number of
      tyrosine residues in the peptide increases. The kinetic study, based on
      spectrophotometric measurements of the surface plasmon resonance optical
      property, shows that the rate of formation of gold nanoparticles was much faster
      at higher pH than at lower pH and was also dependent on the number of tyrosine
      residues present in the peptide. The dityrosine form of the peptide was found to
      retain reducing properties like those of tyrosine in basic medium.

PMID- 16278917
TI  - Development of a ligand knowledge base, part 1: computational descriptors for
      phosphorus donor ligands.
AB  - A prototype collection of knowledge on ligands in metal complexes, termed a
      ligand knowledge base (LKB), has been developed. This contribution describes the
      design of DFT-calculated descriptors for monodentate phosphorus(III) donor
      ligands in a range of representative complexes. Using the resulting data, a
      ligand space is mapped and predictive models are derived for metal complexes.
      Important characteristics, including chemical, computational and statistical
      robustness for the generation and exploitation of such an LKB are described.
      Chemical robustness ensures transferability of the descriptors, as well as
      comprehensive sampling of ligand space. To make the calculations amenable to
      automation in an e-science setting, a reliable, well-defined computational
      approach has been sought from which the descriptors can be readily extracted. The
      LKB has been explored with multivariate statistical methods. Principal component
      analysis (PCA) is used for the mapping of chemical space, projecting multiple
      descriptors into scatter plots which illustrate the clustering of chemically
      similar ligands. Interpretation of the resulting principal components in terms of
      established steric and electronic properties and the importance of its
      statistical robustness to variations in the ligand set are discussed. Multiple
      linear regression (MLR) models have been derived, demonstrating the versatility
      of the descriptors for modeling varied experimentally determined parameters (bond
      lengths, reaction enthalpies and bond-stretching frequencies). The importance of
      re-sampling methods for testing the robustness of predictions is highlighted. A
      strategy for the construction of a robust LKB suitable for the modeling of ligand
      and complex behavior is outlined based on these observations.

PMID- 16278918
TI  - A new approach to enantiopure C3-symmetric molecules.
AB  - Chiral base chemistry has been used to create three chiral centres in one pot on
      a C3-symmetric substrate. The potential of this new approach to C3-symmetric
      molecules is exemplified by the creation of an enantiopure C3v-symmetric triol,
      triphosphane and tripyridine. A ruthenium complex of the last compound has been
      studied by X-ray crystallography.

PMID- 16278919
TI  - Simultaneous determination of glutathione and reactive oxygen species in
      individual cells by microchip electrophoresis.
AB  - A microchip electrophoresis method was developed for simultaneous determination
      of reactive oxygen species (ROS) and reduced glutathione (GSH) in the individual
      erythrocyte cell. In this method, cell sampling, single-cell loading, docking,
      lysing, and capillary electrophoretic separation with LIF detection were
      integrated on a microfluidic chip with crossed channels. ROS was labeled with
      dihydrorhodamine 123 in the intact cell, while GSH was on-chip labeled with 2,3
      naphthalene-dicarboxaldehyde, which was included in the separation medium. On
      chip electrical lysis, characterized by extremely fast disruption of the cellular
      membrane (<40 ms), was exploited to minimize enzymatic effects on analyte
      concentrations during the determination. The microfluidic network was optimized
      to prevent cell leaking from the sample reservoir (S) into separation during the
      separation phase. The structure of the S was modified to avoid blockage of its
      outlet by deposited cells. Detection limits of 0.5 and 6.9 amol for ROS and GSH,
      respectively, were achieved. The average cell throughput was 25 cells/h. The
      effectiveness of the method was demonstrated in the simultaneous determination of
      GSH and ROS in individual cells and the variations of cellular GSH and ROS
      contents in response to external stimuli.

PMID- 16278920
TI  - Chiral separations on multichannel microfluidic chips.
AB  - Chiral separations of FITC-labeled basic drugs on multichannel microfluidic chips
      with LIF detector were investigated. A preliminary screening procedure for seven
      neutral CDs was performed under optimized conditions for chiral separations of
      three FITC-labeled drugs (baclofen, norfenefrine, and tocainide) on a mono
      channel microfluidic chip. According to the results of screening, FITC-baclofen
      and FITC-norfenefrine as well as two chiral selectors including gamma-CD and
      dimethyl-beta-CD (DM-beta-CD) were selected as models to perform chiral
      separations on a two-channel chip. FITC-baclofen enantiomers were separated
      completely by gamma-CD in one channel, while resolution of FITC-norfenefrine
      enantiomers was achieved by DM-beta-CD in the other channel in the same run.
      Furthermore, the feasibility of using one chiral selector to separate multiple
      chiral samples was studied on a four-channel chip. These results show that
      multichannel chip has a potential for chiral high-throughput screening.

PMID- 16278921
TI  - Precolumn diastereomerization and micellar electrokinetic chromatography on a
      plastic microchip: rapid chiral analysis of amino acids.
AB  - Precolumn derivatization and chiral separation of DL-amino acids based on
      diastereomerization have been performed on an integrated poly(dimethylsiloxane)
      microchip. Diastereomeric derivatives were formed in a microfabricated precolumn
      reactor by the reaction of amino acid enantiomers with o-phthaldialdehyde/2,3,4,6
      tetra-O-acetyl-1-thio-beta-D-glucopyranose (OPA/TATG), and separated by MEKC in
      an achiral environment without chiral selectors in the running buffer. Optimized
      precolumn reactions and chiral separations of amino acids were achieved within
      2.5 min. Resolutions of diastereomers of OPA/TATG-amino acids were in the range
      of 2.5-6.1 at optimized separation conditions. Simultaneous separation of a
      mixture of five chiral amino acids was successfully performed in a single run in
      less than 100 s.

PMID- 16278922
TI  - Determination of vitamin C and preservatives in beverages by conventional
      capillary electrophoresis and microchip electrophoresis with capacitively coupled
      contactless conductivity detection.
AB  - The separation and detection of commonly used preservatives (benzoate, sorbate)
      and vitamin C by both conventional CE and microchip electrophoresis with
      capacitively coupled contactless conductivity detection is presented. The
      separation was optimized by adjusting the pH-value of the buffer and the use of
      hydroxypropyl-beta-CD (HP-beta-CD) and CTAB as additives. For conventional CE,
      optimal separation conditions were achieved in a histidine/tartrate buffer at pH
      6.5, containing 0.025% HP-beta-CD and 0.1 mM CTAB. LOD ranged from 0.5 to 3 mg/L
      (S/N = 3) and the RSDs for migration time and peak area were less than 0.1 and
      2%, respectively. A considerable reduction of analysis time can be accomplished
      by using microchip electrophoresis without significant loss in sensitivity under
      optimal separation conditions. A histidine/tartrate buffer at pH 6.5,
      incorporating 0.06% HP-beta-CD and 0.25 mM CTAB, gave detection limits ranging
      between 3 and 10 mg/L and satisfactory reproducibilities of < or =0.4% for the
      migration time and < or =3.5% for the peak area. The methods developed are useful
      for the quantitative determination of food additives in real samples such as soft
      drinks and vitamin C tablets.

PMID- 16278923
TI  - New advances in microchip fabrication for electrochromatography.
AB  - There is a great demand in separation technologies for faster and more effective
      analysis processes. Miniaturization is a suitable technique for satisfying this
      demand as reduction in size gives increased separation speed with higher
      efficiency. CEC is an electric-field-mediated separation technique where the
      liquid flow is generated by the electric field itself. The main advantage of
      using electric field over pressure for flow generation is the flat flow profile
      of the EOF; thus, CEC is one of the best candidates to construct a novel and high
      efficiency microanalytical device. The aim of the present paper is to review the
      basic fabrication and bonding principles, as well as connection and system
      integration options for microfluidics-based electrochromatography. The physical
      structure and fluidic channel formation are critically evaluated, including glass
      microstructuring and fusion bonding. Recent developments in nanoflow measurements
      and the application of various flow control units are also extensively discussed.

PMID- 16278924
TI  - Inadvertent tracheal perforation during thyroidectomy.

PMID- 16278925
TI  - Intestinal absorption characteristics of ketoprofen in rats.
AB  - The present study aims to investigate the intestinal absorption characteristics
      of ketoprofen in rats. The pharmacokinetic profile of ketoprofen was evaluated
      following a single p.o. administration of ketoprofen (1 mg/kg) to rats in the
      absence and presence of benzoic acid or lactic acid (2 and 10 mg/kg), the
      substrates of monocarboxylic acid transporters. The pharmacokinetic profiles of
      ketoprofen (1 mg/kg) were significantly altered by the concurrent use of benzoic
      acid or lactic acid (10 mg/kg), compared with the control (given ketoprofen
      alone). The Cmax and AUC of ketoprofen in the presence of benzoic acid or lactic
      acid (10 mg/kg) were significantly (p<0.05) lower than those from the control
      group, while there was no significant change in Tmax and the terminal plasma half
      life (T1/2) of ketoprofen. These results suggest that ketoprofen shares a common
      transport pathway with benzoic acid and lactic acid during the intestinal
      absorption in rats.

PMID- 16278926
TI  - Comparative bioavailability of two oral formulations of ranitidine.
AB  - The current requirement of the Mexican Authorities to demonstrate the
      interchangeability of ranitidine formulations is to establish that the
      dissolution profile of the drug shows similarity. In order to establish if this
      requirement is adequate, the bioavailability of two formulations that did not
      meet this similarity were compared. Twenty-five female volunteers received 150 mg
      ranitidine (Azantac or Midaven) under fasting conditions in two separate sessions
      using a cross-over design. Plasma samples were obtained at selected times for a
      period of 12 h and stored frozen at -80 degrees C until analysed. Ranitidine
      plasma levels were determined and pharmacokinetic parameters were obtained.
      Values (mean+/-SEM) were: Cmax 528.85+/-25.34 and 563.03+/-33.25 ng/ml, tmax
      2.76+/-0.19 and 2.79+/-0.18 h, and AUC12 h 2694.94+/-99.50 and 2648.51+/-133.38
      ng.h/ml, for Azantac or Midaven, respectively. No statistically significant
      difference was obtained in the parameters evaluated. Moreover, 90% confidence
      limits were 96.6%-116.2% and 90.7%-105.1% for Cmax and AUC12 h ratios,
      respectively, indicating that the formulations tested are bioequivalent, despite
      the dissimilarity in the dissolution profile of the formulations. These results
      suggest that the comparative dissolution profile is not an adequate test to
      demonstrate the interchangeability of ranitidine formulations.

PMID- 16278927
TI  - In vitro inhibitory effects of non-steroidal anti-inflammatory drugs on 4
      methylumbelliferone glucuronidation in recombinant human UDP
      glucuronosyltransferase 1A9--potent inhibition by niflumic acid.
AB  - The inhibitory potencies of non-steroidal anti-inflammatory drugs (NSAIDs) on UDP
      glucuronosyltransferase (UGT) 1A9 activity were investigated in recombinant human
      UGT1A9 using 4-methylumbelliferone (4-MU) as a substrate for glucuronidation. 4
      MU glucuronidation (4-MUG) showed Michaelis-Menten kinetics with a Km value of
      6.7 microM. The inhibitory effects of the following seven NSAIDs were
      investigated: acetaminophen, diclofenac, diflunisal, indomethacin, ketoprofen,
      naproxen and niflumic acid. Niflumic acid had the most potent inhibitory effect
      on 4-MUG with an IC50 value of 0.0341 microM. The IC50 values of diflunisal,
      diclofenac and indomethacin were 1.31, 24.2, and 34.1 microM, respectively, while
      acetaminophen, ketoprofen and naproxen showed less potent inhibition. Niflumic
      acid, diflunisal, diclofenac and indomethacin inhibited 4-MUG competitively with
      Ki values of 0.0275, 0.710, 53.3 and 69.9 microM, respectively, being similar to
      each IC50 value. In conclusion, of the seven NSAIDs investigated, niflumic acid
      was the most potent inhibitor of recombinant UGT1A9 via 4-MUG in a competitive
      manner.

PMID- 16278928
TI  - The effect of increased lipoprotein levels on the pharmacokinetics of
      cyclosporine A in the laboratory rat.
AB  - The response of cyclosporine A (CyA) blood concentrations following changes in
      lipoprotein levels have been inconsistent. Some studies show increases in
      concentrations, whereas others have shown decreases. The intent of this study was
      to examine the effect of two rat models of increased lipoprotein on the
      pharmacokinetics of CyA. One was a simulated high fat content meal, in which 1%
      cholesterol in peanut oil was administered. The other was the poloxamer 407
      induced model of hyperlipidemia. Rats in these two groups were compared to a
      group fasted overnight before the study. In rats given a simulated high fat meal,
      at most time points the mean blood and plasma concentrations were lower, though
      not significantly, compared to fasted animals. Oral lipid led to no significant
      changes in the measured pharmacokinetic parameters of blood or plasma area under
      the concentration vs time curve (AUC), clearance (CL), volume of distribution
      (Vd) or plasma unbound fraction. In the poloxamer 407-treated hyperlipidemic rats
      there were significant reductions in plasma unbound fraction plasma, Vd and
      terminal half-life, but not AUC or CL, compared to normolipidemic rats. In
      contrast, the CL, Vd and t1/2 in the oral lipid-fed rats were all significantly
      higher than the poloxamer 407 treated animals. Oral absolute bioavailability of
      CyA was unchanged by oral lipid. In humans and rats the pharmacokinetics of CyA
      in the face of increased lipoprotein levels do not correspond well to what is
      typically seen for other drugs that are known to bind to lipoproteins.

PMID- 16278929
TI  - Physiological role of D-aspartate oxidase in the assimilation and detoxification
      of D-aspartate in the yeast Cryptococcus humicola.
AB  - The physiological role of D-aspartate oxidase (ChDASPO) in the yeast Cryptococcus
      humicola was analysed through the growth characteristics of a ChDASPO gene
      disrupted strain (daspoDelta) and the expression profile of ChDASPO on various
      combinations of carbon and nitrogen sources. The daspoDelta strain, constructed
      by homologous integration of the yeast URA3 marker, grew as well as the wild-type
      strain on ammonium chloride, L-aspartate or D-alanine as the sole nitrogen
      source. In contrast, the daspoDelta strain did not grow at all on D-aspartate,
      not only as the sole nitrogen source but also as the sole carbon source or as the
      sole nitrogen and carbon source, and grew more slowly than the wild-type strain
      on D-glutamate as the sole nitrogen source. In the wild-type strain, the
      induction of ChDASPO activity strictly depended on the presence of D-aspartate
      and was little affected by the co-presence of ammonium chloride, but it was
      significantly reduced by the co-presence of both glucose and ammonium chloride,
      which, however, did not abolish the induction, allowing considerable expression
      of ChDASPO. This expression pattern was consistent with that shown by Northern
      blot analysis. The daspoDelta strain was more sensitive than the wild-type to the
      growth retardation by acidic D-amino acids, but not to that by the corresponding
      L-isomers or D-alanine. These results clearly show that in the yeast, DASPO plays
      an essential role in the assimilation of D-aspartate and acts as a detoxifying
      agent for D-aspartate.

PMID- 16278930
TI  - Expression of the GPD1 and GPP2 orthologues and glycerol retention during growth
      of Debaryomyces hansenii at high NaCl concentrations.
AB  - The highly NaCl-tolerant yeast Debaryomyces hansenii produces and obtains high
      levels of intracellular glycerol as a compatible solute when grown at high NaCl
      concentrations. The effect of high NaCl concentrations (4%, 8% and 12% w/v) on
      the glycerol production and the levels of intra- and extracellular glycerol was
      determined for two D. hansenii strains with different NaCl tolerance and compared
      to one strain of the moderately NaCl-tolerant yeast Saccharomyces cerevisiae.
      Initially, high NaCl tolerance seems to be determined by enhanced glycerol
      production, due to an increased expression of DhGPD1 and DhGPP2 (AL436338) in D.
      hansenii and GPD1 and GPP2 in S. cerevisiae; however, the ability to obtain high
      levels of intracellular glycerol seems to be more important. The two D. hansenii
      strains had higher levels of intracellular glycerol than the S. cerevisiae strain
      and were able to obtain high levels of intracellular glycerol, even at very high
      NaCl concentrations, indicating the presence of, for example, a type of closing
      channel, as previously described for other yeast species.

PMID- 16278931
TI  - Activation of S phase checkpoint by cigarette smoke extract in
      Schizosaccharomyces pombe.
AB  - Cigarette smoke has long been recognized as a major environmental pollutant that
      can cause significant damage to the cellular macromolecules. Although much is
      known about the types of damage, little is known about the cellular responses to
      the stress caused by cigarette smoke. We have used the fission yeast
      Schizosaccharomyces pombe to elucidate the overall cellular responses towards
      cigarette smoke. Here, we demonstrate that fission yeast cells exposed to aqueous
      extract of cigarette smoke exhibit cell cycle arrest and cell death in a dose
      dependent manner. Cigarette smoke treatment also results in accumulation of
      reactive oxygen species, unusual nuclear morphology and altered cellular
      structure. Our data further establish activation of the S phase checkpoint in
      cigarette smoke-exposed Sz. pombe cells. The checkpoint proteins Rad3, Rad26,
      Rad17, Rad1, Hus1 and Cds1 play key roles in this process, as evidenced by cell
      survival and biochemical analysis, although another checkpoint protein, Rad9,
      seems to be less required. Our results also suggest involvement of the stress
      activated protein kinase Spc1/Sty1 and the bZIP transcription factors Atf1 and
      Pap1 in the cellular response towards cigarette smoke extract. These findings
      indicate activation of the critical S phase checkpoint and cell cycle arrest in
      Sz. pombe following CSE assault.

PMID- 16278932
TI  - Cloning and characterization of a dextranase gene from Lipomyces starkeyi and its
      expression in Saccharomyces cerevisiae.
AB  - A dextranase-encoding cDNA from L. starkeyi KSM22 was isolated and characterized.
      The 2052 bp cDNA fragment (lsd1) harbouring the dextranase gene exhibited one
      open reading frame (ORF) composed of 1824 bp flanked by a 41 bp 5'-UTR and a 184
      bp 3'-UTR, including a 27 bp poly(A) tail. The lsd1 gene contains no introns. The
      open reading frame encodes a 608 amino acid polypeptide (LSD1) with a 67.6 kDa
      predicted molecular mass. There was a 77% deduced amino acid sequence identity
      between the LSD1 dextranase and the dextranase from Penicillium minioluteum. The
      primary structure of LSD1 dextranase exhibits distant similarity with the enzymes
      of the glycosyl hydrolase family 49 that comprises Penicillium dextranase. The
      optimum pH of LSD1 was 6.0 and the optimum temperature was 37 degrees C. LSD1
      dextranase activity was substantially abolished by exposure to 1 mM Hg2+, Ag3+
      and Mn2+. LSD1 exhibited high hydrolysing activity towards dextran (100%),
      soluble starch (22%) and mutan (8%).

PMID- 16278933
TI  - New weakly expressed cell cycle-regulated genes in yeast.
AB  - We present an approach combining bioinformatics prediction with experimental
      microarray validation to identify new cell cycle-regulated genes in Saccharomyces
      cerevisiae. We identify in the order of 100 new cell cycle-regulated genes and
      show by independent data that these genes in general tend to be more weakly
      expressed than the genes identified hitherto. Among the genes not previously
      suggested to be periodically expressed we find genes linked to DNA repair, cell
      size monitoring and transcriptional control, as well as a number of genes of
      unknown function. Several of the gene products are believed to be phosphorylated
      by Cdc28. For many of these new genes, homologues exist in Schizosaccharomyces
      pombe and Homo sapiens for which the expression also varies with cell cycle
      progression.

PMID- 16278935
TI  - Electrospray[+] tandem quadrupole mass spectrometry in the elucidation of ergot
      alkaloids chromatographed by HPLC: screening of grass or forage samples for novel
      toxic compounds.
AB  - Ergot alkaloids are mycotoxins generated by grass and grain pathogens such as
      Claviceps, for example. Ergot alkaloid-poisoning syndromes, such as tall fescue
      toxicosis from endophyte-infected tall fescue grass, are important veterinary
      problems for cattle, horses, sheep, pigs and chickens, with consequent impact on
      food, meat and dairy industries. Damage to livestock is of the order of a billion
      dollars a year in the United States alone. HPLC with UV and fluorescence
      detection are the predominant means of ergot alkaloid determination, with focus
      on quantitation of the marker compound ergovaline, although ELISA methods are
      undergoing investigation. These techniques are excellent for rapid detection, but
      of poor specificity in defining new or poorly characterized ergot alkaloids and
      related compounds. This paper demonstrates the facility of using electrospray(+)
      mass spectrometry with multiple reaction monitoring (MRM) detection during
      chromatographic examination of ergot alkaloid standards of lysergic acid,
      lysergol, ergonovine, ergovaline, ergotamine, ergocornine, ergocryptine and
      ergocrystine by HPLC. Ergoline-8 position epimers could be separated on the
      gradient HPLC system for ergocornine, ergocrystine and ergonovine and appeared as
      shoulders for ergotamine and ergovaline; epimers generally showed different
      patterns of relative intensity for specific MRM transitions. There was reasonable
      correspondence between retention of standards on the 2-mm ESI(+)MS phenyl-hexyl
      based reverse phase column and those on the 4-mm C18-based column. Since up to
      10% of clinical cases involving toxin exposure display unidentified
      chromatographic peaks, 11 samples of feed components associated with such cases
      were studied with developed MRM methods to attempt elucidation of crucial
      components if possible. Ergotamine appeared in all, ergovaline appeared in five
      and ergocornine appeared in six; ergonovine, ergocryptine, ergocrystine and
      lysergol also appeared in several. In addition, molecular weights of compounds
      newly revealed by mass spectrometry suggested ergosine, ergostine and ergoptine
      in four samples, for which standards were not available. Dehydrated products of
      ergotamine, ergocrystine and ergocornine were discovered, along with
      dihydrogenated ergocrystine and ergocryptine in seven of the samples, and the
      issue was raised as to whether dehydration was strictly an instrument-derived
      artifact. Finally, five of the samples, along with fescue seed standard,
      evidenced one or more of 14 new ergot alkaloids ranging in size from 381 to 611
      molecular weight and with key mass spectral characteristics of ergot alkaloids,
      specifically the pair of peaks m/z 223 and 208, corresponding to the ergoline
      ring system and its demethylated variant, respectively. It is anticipated that
      findings such as these will provide impetus to future development of analytical
      methodology for these heretofore relatively rare ergot alkaloid species.

PMID- 16278936
TI  - Dissection of the molecular basis of mycophenolate resistance in Saccharomyces
      cerevisiae.
AB  - IMP dehydrogenase (IMPDH) is required for the de novo synthesis of guanine
      nucleotides. While most invertebrates have one IMPDH gene and humans and mice
      have two, Saccharomyces cerevisiae contains four, IMD1-IMD4. Although Imd2 is 92%
      identical to Imd3, it is the only S. cerevisiae IMPDH that is resistant to
      mycophenolic acid in vitro and is the only one of the four that supports drug
      resistant growth. Thus, S. cerevisiae is unique in possessing two classes of
      IMPDH enzymes with very different drug susceptibilities. The mycophenolate
      sensitive growth phenotype has become an important genetic tool in yeast,
      particularly as an indicator for mutations in the transcription elongation
      machinery. Here we exploit the distinct drug sensitivity of these two closely
      related IMPDH genes to identify the naturally occurring determinants of drug
      resistant growth. Using chimeric IMD2-IMD3 genes in a strain null for IMD genes,
      we show that one of the 39 amino acid differences between these enzymes is
      responsible for much of its drug resistance. The IMP dehydrogenase activity of
      purified chimeric Imd3 containing the Imd2 residue at position 253 was eight-fold
      more resistant than native Imd3. The reciprocal change in Imd2 resulted in a 23
      fold loss of resistance. Hence, acquisition of a hydroxyl side-chain at 523 is
      sufficient to confer a drug-resistant phenotype upon this organism. We identified
      the major determinant of the functional distinction between IMD genes in this
      yeast and suggest that selective pressure on this species forced divergence of
      one member of this gene family toward drug resistance.

PMID- 16278937
TI  - Feedforward neural network models for handling class overlap and class imbalance.
AB  - This paper proposes a framework for training feedforward neural network models
      capable of handling class overlap and imbalance by minimizing an error function
      that compensates for such imperfections of the training set. A special case of
      the proposed error function can be used for training variance-controlled neural
      networks (VCNNs), which are developed to handle class overlap by minimizing an
      error function involving the class-specific variance (CSV) computed at their
      outputs. Another special case of the proposed error function can be used for
      training class-balancing neural networks (CBNNs), which are developed to handle
      class imbalance by relying on class-specific correction (CSC). VCNNs and CBNNs
      are compared with conventional feedforward neural networks (FFNNs), quantum
      neural networks (QNNs), and resampling techniques. The properties of VCNNs and
      CBNNs are illustrated by experiments on artificial data. Various experiments
      involving real-world data reveal the advantages offered by VCNNs and CBNNs in the
      presence of class overlap and class imbalance.

PMID- 16278938
TI  - Theoretical analysis of a TIME-FREQUENCY-PCNN auditory cortex model.
AB  - A particular pulsed neural model of the auditory cortex, the Time-Frequency Pulse
      Coupled Neural Network (TF-PCNN), has shown to decompose its stimulus from the
      cochlea into characteristic pulse-coded time-frequency (TF) stop and pass
      regions. A derived sum of spectrograms representation with these zero- or one
      valued TF weightings has already been applied for the denoising of speech in a
      previous work. This decomposition is now related to the concept of TF projection
      filters, which allows to reinterpret the model equations. The functionality
      imposed by the model equations can so be accessed and justified from a TF signal
      processing perspective, in addition to its biological motivation from
      experimentally observed neurophysiological behavior and simulations.

PMID- 16278939
TI  - A high-order graph generating self-organizing structure.
AB  - A large class of neural network models have their units organized in a lattice
      with fixed topology or generate their topology during the learning process. These
      network models can be used as neighborhood preserving map of the input manifold,
      but such a structure is difficult to manage since these maps are graphs with a
      number of nodes that is just one or two orders of magnitude less than the number
      of input points (i.e., the complexity of the map is comparable with the
      complexity of the manifold) and some hierarchical algorithms were proposed in
      order to obtain a high-level abstraction of these structures. In this paper a
      general structure capable to extract high order information from the graph
      generated by a large class of self-organizing networks is presented. This
      algorithm will allow to build a two layers hierarchical structure starting from
      the results obtained by using the suitable neural network for the distribution of
      the input data. Moreover the proposed algorithm is also capable to build a
      topology preserving map if it is trained using a graph that is also a topology
      preserving map.

PMID- 16278940
TI  - Antenna impedance matching with neural networks.
AB  - Impedance matching between transmission lines and antennas is an important and
      fundamental concept in electromagnetic theory. One definition of antenna
      impedance is the resistance and reactance seen at the antenna terminals or the
      ratio of electric to magnetic fields at the input. The primary intent of this
      paper is real-time compensation for changes in the driving point impedance of an
      antenna due to frequency deviations. In general, the driving point impedance of
      an antenna or antenna array is computed by numerical methods such as the method
      of moments or similar techniques. Some configurations do lend themselves to
      analytical solutions, which will be the primary focus of this work. This paper
      employs a neural control system to match antenna feed lines to two common
      antennas during frequency sweeps. In practice, impedance matching is performed
      off-line with Smith charts or relatively complex formulas but they rarely perform
      optimally over a large bandwidth. There have been very few attempts to compensate
      for matching errors while the transmission system is in operation and most
      techniques have been targeted to a relatively small range of frequencies. The
      approach proposed here employs three small neural networks to perform real-time
      impedance matching over a broad range of frequencies during transmitter
      operation. Double stub tuners are being explored in this paper but the approach
      can certainly be applied to other methodologies. The ultimate purpose of this
      work is the development of an inexpensive microcontroller-based system.

PMID- 16278941
TI  - The use of gas-sensor arrays to diagnose urinary tract infections.
AB  - Sensorial analysis based on the utilisation of human senses, is one of the most
      important and straightforward investigation methods in food and chemical
      analysis. An electronic nose has been used to detect in vivo Urinary Tract
      Infections from 45 suspected cases that were sent for analysis in a UK Health
      Laboratory environment. These samples were analysed by incubation in a volatile
      generation test tube system for 4-5 h. The volatile production patterns were then
      analysed using an electronic nose system with 14 conducting polymer sensors. An
      intelligent model consisting of an odour generation mechanism, rapid volatile
      delivery and recovery system, and a classifier system based on learning
      techniques has been considered. The implementation of an Extended Normalised
      Radial Basis Function network with advanced features for determining its size and
      parameters and the concept of fusion of multiple classifiers dedicated to
      specific feature parameters has been also adopted in this study. The proposed
      scheme achieved a very high classification rate of the testing dataset,
      demonstrating in this way the efficiency of the proposed scheme compared with
      other approaches. This study has shown the potential for early detection of
      microbial contaminants in urine samples using electronic nose technology.

PMID- 16278942
TI  - Neural networks for the optimization of crude oil blending.
AB  - Crude oil blending is an important unit in petroleum refining industry. Many
      blend automation systems use real-time optimizer (RTO), which apply current
      process information to update the model and predict the optimal operating policy.
      The key unites of the conventional RTO are on-line analyzers. Sometimes oil
      fields cannot apply these analyzers. In this paper, we propose an off-line
      optimization technique to overcome the main drawback of RTO. We use the history
      data to approximate the output of the on-line analyzers, then the desired optimal
      inlet flow rates are calculated by the optimization technique. After this off
      line optimization, the inlet flow rates are used for on-line control, for example
      PID control, which forces the flow rate to follow the desired inlet flow rates.
      Neural networks are applied to model the blending process from the history data.
      The new optimization is carried out via the neural model. The contributions of
      this paper are: (1) Stable learning for the discrete-time multilayer neural
      network is proposed. (2) Sensitivity analysis of the neural optimization is
      given. (3) Real data of a oil field is used to show effectiveness of the proposed
      method.

PMID- 16278943
TI  - A multi-clustering fusion scheme for data partitioning.
AB  - A multi-clustering fusion method is presented based on combining several runs of
      a clustering algorithm resulting in a common partition. More specifically, the
      results of several independent runs of the same clustering algorithm are
      appropriately combined to obtain a distinct partition of the data which is not
      affected by initialization and overcomes the instabilities of clustering methods.
      Subsequently, a fusion procedure is applied to the clusters generated during the
      previous phase to determine the optimal number of clusters in the data set
      according to some predefined criteria.

PMID- 16278944
TI  - Full-state tracking control of a mobile robot using neural networks.
AB  - In this paper a nonholonomic mobile robot with completely unknown dynamics is
      discussed. A mathematical model has been considered and an efficient neural
      network is developed, which ensures guaranteed tracking performance leading to
      stability of the system. The neural network assumes a single layer structure, by
      taking advantage of the robot regressor dynamics that expresses the highly
      nonlinear robot dynamics in a linear form in terms of the known and unknown robot
      dynamic parameters. No assumptions relating to the boundedness is placed on the
      unmodeled disturbances. It is capable of generating real-time smooth and
      continuous velocity control signals that drive the mobile robot to follow the
      desired trajectories. The proposed approach resolves speed jump problem existing
      in some previous tracking controllers. Further, this neural network does not
      require offline training procedures. Lyapunov theory has been used to prove
      system stability. The practicality and effectiveness of the proposed tracking
      controller are demonstrated by simulation and comparison results.

PMID- 16278945
TI  - A statistical framework for haplotype block inference.
AB  - The existence of haplotype blocks transmitted from parents to offspring has been
      suggested recently. This has created an interest in the inference of the block
      structure and length. The motivation is that haplotype blocks that are
      characterized well will make it relatively easier to quickly map all the genes
      carrying human diseases. To study the inference of haplotype block
      systematically, we propose a statistical framework. In this framework, the
      optimal haplotype block partitioning is formulated as the problem of statistical
      model selection; missing data can be handled in a standard statistical way;
      population strata can be implemented; block structure inference/hypothesis
      testing can be performed; prior knowledge, if present, can be incorporated to
      perform a Bayesian inference. The algorithm is linear in the number of loci,
      instead of NP-hard for many such algorithms. We illustrate the applications of
      our method to both simulated and real data sets.

PMID- 16278946
TI  - Randomized algorithms for motif detection.
AB  - MOTIVATION: Motif detection for DNA sequences has many important applications in
      biological studies, e.g. locating binding sites regulatory signals, designing
      genetic probes etc. In this paper, we propose a randomized algorithm, design an
      improved EM algorithm and combine them to form a software tool. RESULTS: (1) We
      design a randomized algorithm for consensus pattern problem. We can show that
      with high probability, our randomized algorithm finds a pattern in polynomial
      time with cost error at most x l for each string, where l is the length of the
      motif and can be any positive number given by the user. (2) We design an improved
      EM algorithm that outperforms the original EM algorithm. (3) We develop a
      software tool, MotifDetector, that uses our randomized algorithm to find good
      seeds and uses the improved EM algorithm to do local search. We compare
      MotifDetector with Buhler and Tompa's PROJECTION which is considered to be the
      best known software for motif detection. Simulations show that MotifDetector is
      slower than PROJECTION when the pattern length is relatively small, and
      outperforms PROJECTION when the pattern length becomes large. AVAILABILITY: It is
      available for free at
      http://www.cs.cityu.edu.hk/~lwang/software/motif/index.html, subject to copyright
      restrictions.

PMID- 16278947
TI  - Active site driven ligand design: an evolutionary approach.
AB  - An evolutionary approach for designing a ligand molecule that can bind to the
      active site of a target protein is described in this article. An earlier attempt
      in this regard assumed a fixed tree structure of the ligand on both sides of the
      pharmacophore, and used a genetic algorithm for optimizing the van der Waals
      energy. However, it is evident that knowledge about the size of the tree is
      difficult to obtain an a priori. Moreover, it will also change from one active
      site to another. This limitation is overcome in the present article by using
      variable string length genetic algorithm (VGA) for evolving an appropriate
      arrangement of the basic functional units of the molecule to be designed, whose
      size may now vary. The crossover and mutation operators are appropriately
      redesigned in order to tackle the concept of variable length chromosomes. Once
      the geometry of the molecule is obtained, the possible three-dimensional
      structure and its docking energy is determined. Results are demonstrated for five
      different target proteins both numerically and pictorially. It is found that not
      only does the molecule designed using variable length representation, in general,
      have lower energy values, the docking energies are also lower, as compared to the
      molecule evolved using fixed size representation.

PMID- 16278948
TI  - Multiclass molecular cancer classification by kernel subspace methods with
      effective kernel parameter selection.
AB  - Microarray techniques provide new insights into molecular classification of
      cancer types, which is critical for cancer treatments and diagnosis. Recently, an
      increasing number of supervised machine learning methods have been applied to
      cancer classification problems using gene expression data. Support vector
      machines (SVMs), in particular, have become one of the most effective and leading
      methods. However, there exist few studies on the application of other kernel
      methods in the literature. We apply a kernel subspace (KS) method to multiclass
      cancer classification problems, and assess its validity by comparing it with
      multiclass SVMs. Our comparative study using seven multiclass cancer datasets
      demonstrates that the KS method has high performance that is comparable to
      multiclass SVMs. Furthermore, we propose an effective criterion for kernel
      parameter selection, which is shown to be useful for the computation of the KS
      method.

PMID- 16278949
TI  - Effective algorithms for tag SNP selection.
AB  - Single nucleotide polymorphisms (SNPs), due to their abundance and low mutation
      rate, are very useful genetic markers for genetic association studies. However,
      the current genotyping technology cannot afford to genotype all common SNPs in
      all the genes. By making use of linkage disequilibrium, we can reduce the
      experiment cost by genotyping a subset of SNPs, called Tag SNPs, which have a
      strong association with the ungenotyped SNPs, while are as independent from each
      other as possible. The problem of selecting Tag SNPs is NP-complete; when there
      are large number of SNPs, in order to avoid extremely long computational time,
      most of the existing Tag SNP selection methods first partition the SNPs into
      blocks based on certain block definitions, then Tag SNPs are selected in each
      block by brute-force search. The size of the Tag SNP set obtained in this way may
      usually be reduced further due to the inter-dependency among blocks. This paper
      proposes two algorithms, TSSA and TSSD, to tackle the block-independent Tag SNP
      selection problem. TSSA is based on A* search algorithm, and TSSD is a heuristic
      algorithm. Experiments show that TSSA can find the optimal solutions for medium
      sized problems in reasonable time, while TSSD can handle very large problems and
      report approximate solutions very close to the optimal ones.

PMID- 16278950
TI  - An integrated feature selection and classification method to select minimum
      number of variables on the case study of gene expression data.
AB  - This paper introduces a novel generic approach for classification problems with
      the objective of achieving maximum classification accuracy with minimum number of
      features selected. The method is illustrated with several case studies of gene
      expression data. Our approach integrates filter and wrapper gene selection
      methods with an added objective of selecting a small set of non-redundant genes
      that are most relevant for classification with the provision of bins for genes to
      be swapped in the search for their biological relevance. It is capable of
      selecting relatively few marker genes while giving comparable or better leave-one
      out cross-validation accuracy when compared with gene ranking selection
      approaches. Additionally, gene profiles can be extracted from the evolving
      connectionist system, which provides a set of rules that can be further developed
      into expert systems. The approach uses an integration of Pearson correlation
      coefficient and signal-to-noise ratio methods with an adaptive evolving
      classifier applied through the leave-one-out method for validation. Datasets of
      gene expression from four case studies are used to illustrate the method. The
      results show the proposed approach leads to an improved feature selection process
      in terms of reducing the number of variables required and an increased in
      classification accuracy.

PMID- 16278951
TI  - A quantitative analysis of interfacial amino acid conservation in protein-protein
      hetero complexes.
AB  - A long-standing question in molecular biology is whether interfaces of protein
      protein complexes are more conserved than the rest of the protein surfaces.
      Although it has been reported that conservation can be used as an indicator for
      predicting interaction sites on proteins, there are recent reports stating that
      the interface regions are only slightly more conserved than the rest of the
      protein surfaces, with conservation signals not being statistically significant
      enough for predicting protein-protein binding sites. In order to properly address
      these controversial reports we have studied a set of 28 well resolved hetero
      complex structures of proteins that consists of transient and non-transient
      complexes. The surface positions were classified into four conservation classes
      and the conservation index of the surface positions was quantitatively analyzed.
      The results indicate that the surface density of highly conserved positions is
      significantly higher in the protein-protein interface regions compared with the
      other regions of the protein surface. However, the average conservation index of
      the patches in the interface region is not significantly higher compared with
      other surface regions of the protein structures. This finding demonstrates that
      the number of conserved residue positions is a more appropriate indicator for
      predicting protein-protein binding sites than the average conservation index in
      the interacting region. We have further validated our findings on a set of 59
      benchmark complex structures. Furthermore, an analysis of 19 complexes of antigen
      antibody interactions shows that there is no conservation of amino acid positions
      in the interacting regions of these complexes, as expected, with the variable
      region of the immunoglobulins interacting mostly with the antigens.
      Interestingly, antigen interacting regions also have a higher number of non
      conserved residue positions in the interacting region than the rest of the
      protein surface.

PMID- 16278952
TI  - Fold helical proteins by energy minimization in dihedral space and a DFIRE-based
      statistical energy function.
AB  - Statistical energy functions are discrete (or stepwise) energy functions that
      lack van der Waals repulsion. As a result, they are often applied directly to a
      given structure (native or decoy) without further energy minimization being
      performed to the structure. However, the full benefit (or hidden defect) of an
      energy function cannot be revealed without energy minimization. This paper tests
      a recently developed, all-atom statistical energy function by energy minimization
      with a fixed secondary helical structure in dihedral space. This is accomplished
      by combining the statistical energy function based on a distance-scaled finite
      ideal-gas reference (DFIRE) state with a simple repulsive interaction and an
      improper torsion energy function. The energy function was used to minimize 2000
      random initial structures of 41 small and medium-sized helical proteins in a
      dihedral space with a fixed helical region. Results indicate that near-native
      structures for most studied proteins can be obtained by minimization alone. The
      average minimum root-mean-squared distance (rmsd) from the native structure for
      all 41 proteins is 4.1 A. The energy function (together with a simple clustering
      of similar structures) also makes a reasonable selection of near-native
      structures from minimized structures. The average rmsd value and the average rank
      for the best structure in the top five is 6.8 A and 2.4, respectively. The
      accuracy of the structures sampled and the structure selections can be improved
      significantly with the removal of flexible terminal regions in rmsd calculations
      and in minimization and with the increase in the number of minimizations. The
      minimized structures form an excellent decoy set for testing other energy
      functions because most structures are well-packed with minimum hard-core overlaps
      with correct hydrophobic/hydrophilic partitioning. They are available online at
      http://theory.med.buffalo.edu.

PMID- 16278953
TI  - Rank-based methods as a non-parametric alternative of the T-statistic for the
      analysis of biological microarray data.
AB  - We have recently introduced a rank-based test statistic, RankProducts (RP), as a
      new non-parametric method for detecting differentially expressed genes in
      microarray experiments. It has been shown to generate surprisingly good results
      with biological datasets. The basis for this performance and the limits of the
      method are, however, little understood. Here we explore the performance of such
      rank-based approaches under a variety of conditions using simulated microarray
      data, and compare it with classical Wilcoxon rank sums and t-statistics, which
      form the basis of most alternative differential gene expression detection
      techniques. We show that for realistic simulated microarray datasets, RP is more
      powerful and accurate for sorting genes by differential expression than t
      statistics or Wilcoxon rank sums - in particular for replicate numbers below 10,
      which are most commonly used in biological experiments. Its relative performance
      is particularly strong when the data are contaminated by non-normal random noise
      or when the samples are very inhomogenous, e.g. because they come from different
      time points or contain a mixture of affected and unaffected cells. However, RP
      assumes equal measurement variance for all genes and tends to give overly
      optimistic p-values when this assumption is violated. It is therefore essential
      that proper variance stabilizing normalization is performed on the data before
      calculating the RP values. Where this is impossible, another rank-based variant
      of RP (average ranks) provides a useful alternative with very similar overall
      performance. The Perl scripts implementing the simulation and evaluation are
      available upon request. Implementations of the RP method are available for
      download from the authors website (http://www.brc.dcs.gla.ac.uk/glama).

PMID- 16278954
TI  - Mining time-dependent gene features.
AB  - This paper presents an application of the Independent Component Analysis (ICA)
      method to genomic data. In particular, experimentally produced perturbation
      effects over the E.coli bacterium are monitored through the changes of gene
      expression values observed at regular times, and until steady state has been
      reached. The aim is to control the response of the SOS system to DNA damage. We
      might assume that only part of the genetic regulatory network is affected
      directly by the perturbation conditions, as indirect cascade effects might also
      be present, and some genes may change just because of randomness. ICA decomposes
      the gene matrix and identifies groups of genes belonging to a certain estimated
      component by virtue of co-expression; it is of course of interest to establish co
      regulation dynamics, which might underlie the captured correlation. Stronger
      forms of dependence, like Mutual Information, are thus computed and compared with
      linear correlation in order to validate the results and establish the role of the
      identified components in determining the network dynamics.

PMID- 16278955
TI  - Neural models for predicting viral vaccine targets.
AB  - We applied artificial neural networks (ANN) for the prediction of targets of
      immune responses that are useful for study of vaccine formulations against viral
      infections. Using a novel data representation, we developed a system termed
      MULTIPRED that can predict peptide binding to multiple related human leukocyte
      antigens (HLA). This implementation showed high accuracy in the prediction of the
      promiscuous peptides that bind to five HLA-A2 allelic variants. MULTIPRED is
      useful for the identification of peptides that bind multiple HLA-A2 variants as a
      group. By implementing ANN as a classification engine, we enabled both the
      prediction of peptides binding to multiple individual HLA-A2 molecules and the
      prediction of promiscuous binders using a single model. The ANN MULTIPRED
      predicts peptide binding to HLA-A*0205 with excellent accuracy (area under the
      receiver operating characteristic curve--AROC>0.90), and to HLA-A*0201, HLA
      A*0204 and HLA-A*0206 with high accuracy (AROC>0.85). Antigenic regions with high
      density of binders ("antigenic hot-spots") represent best targets for vaccine
      design. MULTIPRED not only predicts individual 9-mer binders but also predicts
      antigenic hot spots. Two HLA-A2 hot-spots in Severe Acute Respiratory Syndrome
      Coronavirus (SARS-CoV) membrane protein were predicted by using MULTIPRED.

PMID- 16278956
TI  - A hybrid genetic algorithm and expectation maximization method for global gene
      trajectory clustering.
AB  - Clustering time-course gene expression data (gene trajectories) is an important
      step towards solving the complex problem of gene regulatory network modeling and
      discovery as it significantly reduces the dimensionality of the gene space
      required for analysis. Traditional clustering methods that perform hill-climbing
      from randomly initialized cluster centers are prone to produce inconsistent and
      sub-optimal cluster solutions over different runs. This paper introduces a novel
      method that hybridizes genetic algorithm (GA) and expectation maximization
      algorithms (EM) for clustering gene trajectories with the mixtures of multiple
      linear regression models (MLRs), with the objective of improving the global
      optimality and consistency of the clustering performance. The proposed method is
      applied to cluster the human fibroblasts and the yeast time-course gene
      expression data based on their trajectory similarities. It outperforms the
      standard EM method significantly in terms of both clustering accuracy and
      consistency. The biological implications of the improved clustering performance
      are demonstrated.

PMID- 16278957
TI  - Italian AIDS vaccine candidate advances into Phase II trials.

PMID- 16278958
TI  - Russian AIDS vaccine candidate approved for human testing.

PMID- 16278959
TI  - Funding. Coalition launches campaign to reauthorize Ryan White CARE Act.

PMID- 16278960
TI  - Immigration. African's petition for review of asylum denied on appeal.

PMID- 16278961
TI  - Transfusion. $900,000 payout for HIV blood error in England.

PMID- 16278962
TI  - Disclosure. Court: threat to disclose serostatus constitutes stalking.

PMID- 16278963
TI  - Prisons. HIV prevention trumps First Amendment behind bars.

PMID- 16278964
TI  - Needle exchange. HIV prevention programs dealt setback in New Jersey.

PMID- 16278965
TI  - Within- and between-day stability of treadmill walking VO2 in children with
      hemiplegic cerebral palsy. Stability of walking VO2 in children with CP.
AB  - Within- and between-day stability in locomotor energy use was quantified in 13
      children with hemiplegic CP. During testing, subjects were familiarized with the
      laboratory environment (Session 1), performed three 5-min level treadmill walks
      (Trials 1, 2, and 3) at 0.67 m x s-1 (Session 2), and completed a single 5-min
      walk (Trial 4) at 0.67 m x s-1 (Session 3). In Sessions 2 and 3, HR was assessed
      and expired air was collected and analyzed to determine VO2. Data analyses
      revealed no significant difference (P > 0.05) in either net VO2 (ml x kg-1 x min
      1) or EEIHR (b x m-1) across the three trials performed in Session 2 and between
      average measures of net VO2 and EEIHR quantified in Session 2 and those obtained
      in Session 3. Mean within-day coefficient of variation (CV) values for net VO2
      and EEIHR were 8.6% +/- 8.5% and 13.9% +/- 7.8%, respectively. Analysis of
      between-day variability and energy expenditure revealed a between-day CV value of
      13.1% for net VO2 and 24.0% for EEIHR. In addition, significant inverse
      relationships between GMFM scores and within-day (r = -0.61) and between-day (r =
      -0.58) CV values for net VO2 were detected. Viewed in concert, these data suggest
      that fairly stable within- and between-day measures of locomotor energy
      expenditure during level treadmill walking can be achieved in subjects with
      hemiplegic CP if testing is preceded by a short period of treadmill
      accommodation. However, children with greater motor dysfunction may require an
      extended period of treadmill accommodation to reduce trial-to-trial variability
      in walking energy use.

PMID- 16278967
TI  - Bibliography current world literature. Transfusion medicine.

PMID- 16278966
TI  - Trunk sway measurements during stance and gait tasks in Parkinson's disease.
AB  - To achieve a unified assessment of postural instability in Parkinson's disease
      (PD) over a range of clinical stance and gait tasks, which may provide an insight
      into a tendency to fall, we measured trunk sway in the anterior-posterior and
      medial-lateral directions in freely moving PD patients and age-matched controls.
      We also measured task duration as time to complete the task or time to loss of
      balance. Patients had larger amplitudes of trunk sway velocities for stance tasks
      (e.g. mean pitch velocity when standing on two-legs eyes closed equalled 19.1 +/-
      6.4 for PD patients on medication versus 4.8 +/- 0.3 degrees/s for controls, p =
      0.0003) and for an expected (following prior warning) retropulsion test (mean
      roll angle equalled 4.3 +/- 0.5 degrees for PD patients versus 2.2 +/- 0.6
      degrees for controls, p = 0.0003) than controls. Patients were more likely to
      fall earlier for stance tasks, and took longer to complete gait tasks (e.g.
      walking 3 m eyes closed, mean time 6.8 +/- 0.6 sees versus 4.9 +/- 0.1 sees, p =
      0.0001). These differences between patients and controls were, in most cases,
      independent of medication. Based on these results we defined a simple test
      battery of stance and gait tasks that could discriminate between PD patients who
      had recent falls and controls. These results indicate that trunk sway measures
      recorded during stance and gait tasks provide useful information on balance
      deficits leading to falls in PD patients.

PMID- 16278968
TI  - Evidence-based emergency medicine/systematic review abstract. To dive or not to
      dive? Use of hyperbaric oxygen therapy to prevent neurologic sequelae in patients
      acutely poisoned with carbon monoxide.

PMID- 16278969
TI  - Evidence-based emergency medicine/rational clinical examination abstract.
      Diagnosing pneumonia by medical history and physical examination.

PMID- 16278970
TI  - Sacred disease secrets revealed: the genetics of human epilepsy.
AB  - Neurons throughout the brain suddenly discharging synchronously and recurrently
      cause primarily generalized seizures. Discharges localized awhile in one part of
      the brain cause focal-onset seizures. A genetically determined generalized
      hyperexcitability had been predicted in primarily generalized seizures, but
      surprisingly the first epilepsy gene discovered, CHRNA4, was in a focal (frontal
      lobe)-onset syndrome. Another surprise with CHRNA4 was its encoding of an ion
      channel present throughout the brain. The reason why CHRNA4 causes focal-onset
      seizures is unknown. Recently, the second focal (temporal lobe)-onset epilepsy
      gene, LGI1 (unknown function), was discovered. CHRNA4 led the way to mutation
      identifications in 15 ion channel genes, most causing primarily generalized
      epilepsies. Potassium channel mutations cause benign familial neonatal
      convulsions. Sodium channel mutations cause generalized epilepsy with febrile
      seizures plus or, if more severe, severe myoclonic epilepsy of infancy. Chloride
      and calcium channel mutations are found in rare families with the common
      syndromes childhood absence epilepsy and juvenile myoclonic epilepsy (JME).
      Mutations in the EFHC1 gene (unknown function) occur in other rare JME families,
      and yet in other families, associations are present between JME (or other
      generalized epilepsies) and single nucleotide polymorphisms in the BRD2 gene
      (unknown function) and the malic enzyme 2 (ME2) gene. Hippocrates predicted the
      genetic nature of the 'sacred' disease. Genes underlying the 'malevolent' forces
      seizing 1% of humans have now been revealed. These, however, still account for a
      mere fraction of the genetic contribution to epilepsy. Exciting years are ahead,
      in which the genetics of this extremely common, and debilitating, neurological
      disorder will be solved.

PMID- 16278971
TI  - Is it necessary to admit low-risk patients with suspected acute coronary syndrome
      to inpatient telemetry beds?

PMID- 16278972
TI  - Molecular pathogenesis of Parkinson's disease.
AB  - Parkinson's disease (PD) is a common and incurable neurodegenerative disease,
      affecting 1% of the population over the age of 65. Despite a well-described
      clinical and pathological phenotype, the molecular mechanisms which lead to
      neurodegeneration remain elusive. However, there is a wealth of evidence from
      both toxin based models and genetic based models, which suggest a major etiologic
      role for mitochondrial dysfunction, protein aggregation, the ubiquitin-proteasome
      system and kinase signalling pathways in the pathogenesis of PD. Ultimately, an
      understanding of the molecular events which precipitate neurodegeneration in
      idiopathic PD will enable the development of targeted and effective therapeutic
      strategies. We review the latest evidence for the proposed molecular processes
      and discuss their relevance to the pathogenesis of sporadic PD.

PMID- 16278973
TI  - In hurricanes' aftermath, keeping infection under control.

PMID- 16278974
TI  - Lawsuit against HIV/AIDS funding policy.

PMID- 16278975
TI  - Proceedings and abstracts of the 5th International Meeting on Metabotropic
      Glutamate Receptors.

PMID- 16278977
TI  - [BPL and the current status of the CAO].

PMID- 16278976
TI  - [The records of the Medical Faculty of the University of Leipzig on the Woyzeck
      case, discovered again after 180 years].
AB  - Through Georg Buchner's drama the case of Johann Christian Woyzeck gained
      worldwide fame. For the first time ever this study presents the testimonial drawn
      up by the Medical Faculty of Leipzig University, which until now had been
      regarded as having been lost. Now, however, the first-named author rediscovered
      it in the files of the Leipzig University Archives. The testimonial proved to be
      a decisive importance, as it sealed Woyzeck's execution in 1824. Before
      presenting major passages from the testimonial this study give an overview of the
      chronology of the Woyzeck case and the other medico-psychiatric testimonials
      drawn up by Leipzig municipal physician Johann Christian August Clarus. It also
      reveals which professors of Leipzig Medical Faculty were involved in drawing up
      the final testimonial which confirmed Clarus's findings and rejected the
      objections raised by Woyzeck's counsel - remarkably without examining the
      offender himself first-hand, but merely relying on and evaluating the
      testimonials drawn up by Clarus.

PMID- 16278978
TI  - Our oral health improves. CDC/NIH report cites progress, disparities.

PMID- 16278979
TI  - Do doctors practice what is preached? A survey of the Harvard Medical School
      faculty shows that, yes, mainly they do. Healthy habits and low BMIs prevail.

PMID- 16278980
TI  - Aspirin: quitting cold turkey could be dangerous. Studies have linked aspirin
      withdrawal to heart attacks.

PMID- 16278981
TI  - Cancer protection.

PMID- 16278982
TI  - By the way, doctor. Do you think flu shots might also prevent lung cancer?

PMID- 16278983
TI  - By the way, doctor. Is there a brain scan that can specifically diagnose
      Alzheimer's disease?

PMID- 16278984
TI  - Developmental data in preschool children born after prolonged pregnancy.
AB  - AIM: To evaluate children born post-term (gestational age>or=42 weeks) with
      respect to developmental data obtained at the ages of 4 and 5.5 y. METHODS: The
      study population included all children (n=354) born in 1991 at Huddinge
      University Hospital with a gestational age of >or=42 wk. The births were
      identified and perinatal data were collected through the Swedish National Birth
      Registry. Developmental assessments from the child health centres were analysed.
      Children born at term, but before a gestational age of 42 wk, served as controls.
      Logistic regression analysis was used to analyse the data. RESULTS: Children born
      post-term had more developmental deviations than the controls (estimated odds
      ratio 2.20; 95% CI: 1.29-3.85). Boys had more deviations than girls (estimated
      odds ratio 1.92; 95% CI: 1.11-3.45). CONCLUSION: Our results indicate that there
      might be an association between post-term birth and developmental deviations.

PMID- 16278985
TI  - A non-handicapped cohort of low-birthweight children: growth and general health
      status at 11 years of age.
AB  - AIMS: To describe and compare physical growth, current health status, functional
      limitations and neurodevelopmental impairments (defined as low IQ, school
      problems or psychiatric disorder) at 11 y of age in a population of non
      handicapped low-birthweight (LBW) children with that of normal-birthweight (NBW)
      children. METHODS: A population-based sample of 130 LBW children (weighing less
      than 2000 g at birth) without major handicaps, and a random sample of 131 NBW
      children born at term. Somatic and mental health and cognitive abilities were
      assessed through questionnaires to parents, a physical examination, standardized
      tests of cognitive function (WISC-R) and a semi-structured interview (Children
      Assessment Schedule). RESULTS: General somatic health status was similar for the
      LBW and NBW children. The LBW children were shorter (mean difference -2.5 cm; 95%
      CI -0.9 to -4.2) and had a smaller head circumference (mean difference -0.8 cm;
      95% CI -0.4 to -1.1) but similar weights and body mass indices. Differences and
      similarities in anthropometric measures were the same at 5 and 11 y of age. The
      LBW children had higher systolic (mean difference 3.2 mmHg; 95% CI -0.6 to -0.3)
      but similar diastolic blood pressure. A higher proportion of LBW children had
      decreased visual acuity and hearing impairment. Forty per cent of LBW children
      had neurodevelopmental impairments, compared to 20% of NBW children (OR 2.6; 95%
      CI 1.5 to 4.5). CONCLUSION: At 11 y of age, survivors of moderately low
      birthweight without major handicaps may have generally good health, but are at
      risk of neurodevelopmental impairments.

PMID- 16278987
TI  - Behavioural effects of phenylalanine-free amino acid tablet supplementation in
      intellectually disabled adults with untreated phenylketonuria.
AB  - AIM: To evaluate the effects of phenylalanine (Phe)-free essential amino acid
      (AA) tablets enriched in tyrosine and tryptophan on the performance of
      intellectually disabled adult patients with untreated phenylketonuria (PKU).
      METHODS: Phe-free AA tablets and placebo tablets were administered to 19
      untreated PKU subjects on a normal diet for 6 mo in a prospective double-blinded
      crossover study. The adaptive behaviour of the patients was tested prior to the
      study and at 6 and 12 mo after the start, using a simplified version of the
      Vineland Adaptive Behaviour Scale. For each sub-domain, the patients were rated
      either "0" (for poor performance) or "1" (for good performance). Neurological
      signs and symptoms and specific behavioural characteristics were recorded monthly
      by caretakers. Every 6 mo, neurological examination of the patients was
      performed, and the caretakers were interviewed. The statistical significance of
      the results was tested by means of the Fisher's exact and Wilcoxon tests.
      RESULTS: The most significant changes were an improved concentration and the
      development of a meaningful smile, which were observed in 44% and 43% of the
      patients on AA tablet treatment, respectively, but not patients on placebo. Other
      important but less significant changes included increased awareness of external
      stimuli (63%) and less self-injury (43%), and 40% were smiling and laughing
      occasionally. The mean overall rating increased from an initial value of 6.3 to
      10.1 in patients when on AA tablet treatment (p=0.002), and to 7.0 in patients
      when on placebo (p=0.068). The difference between active AA treatment and placebo
      was statistically significant (p=0.027). CONCLUSIONS: This pilot study suggests
      that Phe-free AA tablets enriched in tyrosine and tryptophan may improve the
      quality of life in some intellectually disabled adults with untreated PKU.

PMID- 16278986
TI  - Cefuroxime axetil versus placebo for children with acute respiratory infection
      and imaging evidence of sinusitis: a randomized, controlled trial.
AB  - AIM: To evaluate the efficacy of antibiotic treatment in children who presented
      in medical care with respiratory infection and had imaging evidence of sinusitis.
      METHODS: Eighty-two children (4-10 y) with acute respiratory symptoms and
      ultrasonography findings suggestive of acute rhinosinusitis were enrolled in a
      randomized, double-blind trial. The sinus findings were confirmed with plain
      radiographs. The children received either cefuroxime axetil in 125-mg capsules
      twice a day for 10 d or placebo. Main outcome measures were complete cure in 2 wk
      and absence of prolonged symptoms or complications. RESULTS: A total of 72
      children (88%) completed follow-up. The sinusitis findings in the ultrasound
      could be confirmed with plain radiographs in 65 of the 72 patients (90%). The
      proportion of children completely cured by day 14 was similar in both groups
      (difference 6%, 95% confidence interval -16% to 29%). Similarly, there was no
      significant difference in the proportions of children who escaped prolonged
      disease and complications between the groups (difference 7%, -9% to 24%).
      CONCLUSION: A 10-d course of cefuroxime axetil offered no clinical benefit to
      children with an acute respiratory illness and imaging evidence of acute
      sinusitis.

PMID- 16278988
TI  - Erythrocyte membrane acetylcholinesterase, Na+, K+-ATPase and Mg2+-ATPase
      activities in patients with classical galactosaemia.
AB  - BACKGROUND: Classical galactosaemia is commonly presented by high blood galactose
      (Gal) and galactose-1-phosphate (Gal-1-P) levels followed by mental retardation,
      seizures, etc. dependent on the mutation of the patients. AIM: To evaluate Gal
      and Gal-1-P in the blood of patients and to correlate their levels with their
      erythrocyte membrane acetylcholinesterase (AChE), Na+,K+-ATPase and Mg2+-ATPase
      activities. METHODS: Blood was obtained from nine patients on poor diet (group B)
      followed by a 30-d strict diet (group A) and controls (group C) in order to
      evaluate Gal and Gal-1-P in Guthrie cards and to correlate their concentrations
      with the above enzyme activities, which were measured spectrophotometrically.
      RESULTS: With the patients on a "loose" diet, AChE, Na+,K+-ATPase and Mg2+-ATPase
      activities were found to be decreased, as compared with those on strict diet and
      controls. Significantly (p<0.01) inverse correlation coefficients of the enzyme
      activities were found with Gal-1-P levels. CONCLUSION: (a) AChE, Na+,K+-ATPase
      and Mg2+-ATPase activities were determined to be decreased in poorly controlled
      patients with classical galactosaemia. (b) The enzyme activities were inversely
      correlated with the Gal-1-P blood levels. (c) Since Na+,K+-ATPase in the
      erythrocyte membranes is the isomer of Na+,K+-ATPase distributed in many tissues
      and in the brain, evaluation of the enzyme activity in the erythrocytes could be
      a useful peripheral marker of Gal-1-P toxicity.

PMID- 16278989
TI  - Intra- and interindividual variability of glucuronidation of paracetamol during
      repeated administration of propacetamol in neonates.
AB  - BACKGROUND: Major changes in drug clearance and metabolism are observed during
      infancy, in part based on ontogenic regulation of various metabolic pathways.
      Since paracetamol provides a good substrate to study UGT (1A6) activity, urinary
      metabolites of propacetamol were determined in neonates in whom propacetamol was
      repeatedly administered. METHODS: Paracetamol glucuronide (APAP-G), paracetamol
      sulphate (APAP-S) and free paracetamol were determined in urine samples of
      neonates during repeated administration of propacetamol. Spearman rank and linear
      multiple regression (MedCalc, Mariakerke, Belgium) were used to study the effect
      of postnatal age, of postconceptional age and of repeated administration on the
      relative contribution of APAP-G to overall urine paracetamol (APAP-G+APAP-S+free
      paracetamol) elimination (G/T ratio). RESULTS: 147 samples were collected in 23
      neonates. Molar median G/T ratio was 14% (range 1-53). Besides increasing G/T
      ratio with increasing postnatal (p<0.0001) and postconceptional age (p<0.01),
      repeated administration (p<0.01) also correlated with an increasing G/T ratio,
      and repeated administration remained significant (p<0.01) after correction of
      postnatal and postconceptional age in a multiple regression model. CONCLUSION:
      Major variability in the ontogeny of UGT activity to overall elimination of
      paracetamol was documented in neonates. Besides postnatal and postconceptional
      age, a significant effect of repeated administration on UGT activity was
      documented.

PMID- 16278990
TI  - Birth centre care over a 10-year period: infant morbidity during the first month
      after birth.
AB  - AIM: To study morbidity during the first month of life affecting infants of
      mothers booked for birth centre care during pregnancy. METHODS: 3238 live single
      born infants whose mothers were admitted to an in-hospital birth centre, located
      at South Hospital in Stockholm, between 1989 and 2000 were compared with 179,502
      infants whose mothers received standard maternity care in the Stockholm region
      during the same period, and who fulfilled the same medical inclusion criteria as
      those of the birth centre group. Information on other exposures and outcomes was
      collected from the Swedish Medical Birth and Hospital Discharge Registers.
      Logistic regression analyses were performed to calculate the odds ratio (OR),
      using 95% confidence intervals (95% CI). RESULTS: Compared with infants born in
      standard care, infants in the birth centre group had a higher risk of respiratory
      problems (OR 1.39; 95% CI 1.14-1.69), a difference correlated to less serious
      respiratory diagnoses. However, the difference was not statistically significant
      if the birth centre group was compared only with infants born in standard care at
      South Hospital (OR 1.18; 95% CI 0.94-1.47). Birth centre care was associated with
      a lower risk of fractures (OR 0.40; 95% CI 0.25-0.63). CONCLUSION: Birth centre
      care was not associated with severe infant morbidity and even appeared to reduce
      the risk of birth trauma, such as clavicle and other fractures.

PMID- 16278991
TI  - Use of supplementary equipment for resuscitation of newborn infants at tertiary
      perinatal centres in Australia and New Zealand.
AB  - AIM: Neonatal resuscitation is a common and important intervention. International
      consensus statements advise how newborns should be resuscitated and suggest
      equipment to be used. Use of equipment not specifically recommended in these
      guidelines has been advocated. We wished to determine how widely this
      supplementary equipment is used in a geographically defined region. METHODS: Each
      of the 25 tertiary perinatal centres with on-site deliveries in Australia and New
      Zealand was surveyed. The questionnaire asked about the use of the following
      items during delivery room resuscitation: pulse oximetry, exhaled carbon dioxide
      detection, polyethylene wrapping, oxygen blenders, laryngeal mask and
      oropharyngeal airways. RESULTS: Data were obtained from all centres. Pulse
      oximetry is used at 12 (48%) centres. Exhaled CO2 detection is used to confirm
      endotracheal tube placement at three (12%) of the centres. Polyethylene wrapping
      is used to prevent heat loss in very-low-birthweight infants at delivery at 11
      (44%) centres. Oxygen blenders are used to modify the amount of oxygen delivered
      at nine (36%) centres. Laryngeal mask airways are infrequently used at two (8%)
      centres. Oropharyngeal airways are infrequently used at five (20%) centres.
      CONCLUSION: There is considerable variation in the equipment and techniques used
      to resuscitate newly born infants. Use of equipment not specifically recommended
      in international consensus statements is widespread. These are potentially
      effective tools to improve resuscitation. The evidence supporting their use is,
      however, limited. Urgent evaluation of their efficacy and safety is required
      before even more widespread use occurs.

PMID- 16278992
TI  - Early post-convulsive prolongation of QT time in children.
AB  - AIM: An important differential diagnosis of seizures in childhood is the long QT
      syndrome. Childhood epilepsy occurs about 400 times more often than long QT
      syndrome. We had observed children with slight post-convulsive prolongation of QT
      time more often than the reported incidence of long QT syndrome. We therefore
      conducted a prospective study to define the characteristics of post-convulsive
      prolongation of QT time in children. METHODS: We investigated 30 consecutive
      infants and children (3 mo to 14 y) within 2 h after seizures. A follow-up ECG
      was obtained 1-9 d later. We also obtained ECGs from 30 healthy age- and gender
      matched controls. We calculated the QT interval corrected for heart rate (QTc) by
      Bazett's formula in leads II, V5, V6, QT dispersion and the number of notched T
      waves. RESULTS: We found a QTc interval of more than 440 ms in one or more leads
      in the first ECG in seven of 30 infants and children compared to 1 of 30 in the
      follow-up ECG (p=0.0003) and two of 30 in the healthy controls (p=0.14). Average
      QTc was higher for all leads in the first ECG. This was statistically significant
      in leads II (414 vs 402 ms, p=0.008), V5 (416 vs 404 ms, p=0.002) and V6 (415 vs
      399 ms, p=0.001). Compared to healthy controls, QT dispersion was slightly larger
      in the early post-convulsive ECG (36 vs 31 ms, p=0.03). Notched T waves occurred
      more frequently in the early compared to the late post-convulsive ECGs (p=0.009).
      CONCLUSION: Slight to moderate post-convulsive prolongation of the QT interval is
      not rare but transient in paediatric patients.

PMID- 16278993
TI  - Autonomic nervous system functions in children with breath-holding spells and
      effects of iron deficiency.
AB  - AIM: To analyse the activity of the autonomic nervous system during breath
      holding spells, we assessed the ECG changes, including ventricular repolarization
      parameters before and during the spell. We also analysed the effects of iron
      deficiency on these ECG parameters. METHODS: The study group consisted of 37
      children with breath-holding spells (30 cyanotic, 7 pallid) (mean age+/-SD:
      12.9+/-10.8 mo). Twenty-six healthy children (mean age+/-SD: 14.4+/-8.6 mo)
      served as a control group. All patients and controls had standard 12-lead
      simultaneous surface ECG. All patients had ECG recordings during at least one
      severe breath-holding spell obtained by "event recorder". Traces obtained by
      "event recorder" were analysed in terms of mean heart rate and the frequency and
      duration of asystole during the spell. RESULTS: Respiratory sinus arrhythmia on
      standard ECGs and asystole frequency during spells were higher in patients with
      pallid breath-holding spells. Patients with iron deficiency had a lower frequency
      of respiratory sinus arrhythmia and prolonged asystole time during the spell.
      There was no difference in terms of ventricular repolarization parameters (QT/QTc
      intervals and QT/QTc dispersions) between patients and controls and between
      patient subgroups (cyanotic versus pallid). CONCLUSION: These results confirmed
      the presence of autonomic dysregulation in children with breath-holding spells.
      Iron deficiency may have an impact on this autonomic dysregulation. Ventricular
      repolarization was unaffected in patients with breath-holding spells.

PMID- 16278994
TI  - Outcome in neonates with congenital heart disease referred for respiratory
      extracorporeal membrane oxygenation.
AB  - AIM: To evaluate the proportion of neonates referred for extracorporeal membrane
      oxygenation (ECMO) support in the modern era of advanced conventional treatments
      for respiratory failure who actually had congenital heart disease (CHD), and to
      assess the impact of this diagnostic route on patient condition and outcome.
      METHODS: A retrospective case-note review of neonatal ECMO and cardiac admissions
      to a single, tertiary ECMO and cardiac intensive care unit (ICU) between March
      1999 and February 2002. RESULTS: 287 symptomatic neonates presented to the ICU
      with previously undiagnosed cardiac or respiratory disease. Eighty-two with
      presumed respiratory failure were referred for ECMO, and 205 with suspected CHD
      were referred for cardiac evaluation. Eight (10%) ECMO referrals, all with
      presumed persistent pulmonary hypertension of the newborn (PPHN), were found to
      have CHD (transposition: 3; total anomalous pulmonary venous connection: 3; left
      heart obstructive lesions: 2). Mortality in this group was 50%, compared with 11%
      for correctly identified CHD patients (odds ratio 8.2, 95% CI 1.92, 35.4,
      p<0.01). For all neonates with CHD, the risk of death was increased by the
      presence of cardiovascular collapse and end-organ dysfunction at presentation to
      the ICU (p<0.01 for both). CONCLUSION: Neonates with CHD may present as severe
      "PPHN" via the ECMO service. Poor outcome in these patients relates to the high
      incidence of cardiovascular collapse and end-organ dysfunction. Early
      echocardiography is recommended for neonates with presumed PPHN. Neonatal ECMO
      support should be based in centres with cardiac surgical services.

PMID- 16278995
TI  - Mothers' experiences of child health clinic services in Sweden.
AB  - AIM: To investigate women's experiences of child health clinic (CHC) care and
      risk factors for being dissatisfied. Experiences of specific aspects of care were
      further explored in subgroups of women who were not generally satisfied. METHODS:
      All Swedish-speaking women admitted to any of the approximately 600 antenatal
      clinics in Sweden during 3 wk evenly spread over 1 y in 1999 and 2000 were
      invited to participate in the study. Altogether, 3113 women agreed to
      participate. Data were collected by questionnaires: in early pregnancy, 2 mo and
      1 y postpartum, and from the Swedish Medical Birth Register. For the purpose of
      this study, data from the 2415 women who answered the question used as the
      principal outcome in this study, i.e. overall satisfaction with CHC care, were
      analysed. RESULTS: Psychological factors, such as maternal depressive symptoms
      and worry about caring for the newborn, and serious infant feeding problems were
      predictors of less satisfied or mixed feelings about CHC care. About one in three
      women were dissatisfied with the attention paid to their own needs, and a similar
      proportion said information about vaccinations was insufficient. Of the four
      subgroups-mothers whose babies had feeding problems and mothers with depressive
      symptoms at 2 mo, 1 y, and on both occasions-the latter group was the least
      satisfied with the nurse and the time allocated to various issues. CONCLUSIONS:
      Swedish mothers appear to be satisfied with the attention given to their infants
      at CHCs, but many feel that their own needs as new mothers are neglected. This
      study supports current development towards screening for maternal depression at
      CHCs.

PMID- 16278996
TI  - Low-birthweight adolescents: quality of life and parent-child relations.
AB  - AIM: To explore the effect of low birthweight on quality of life, the parent
      child relationship and the parents' mental health. DESIGN/STUDY GROUPS: A
      population-based follow-up of 56 very-low-birthweight (<or=1500 g), 60 term small
      for-gestational-age (birthweight<10th centile) and 83 term control adolescents
      (birthweight>or=10th centile) at 14 y of age. OUTCOME MEASURES: Child Health
      Questionnaire (Child Form, Parent Form), Parental Bonding Instrument rated by
      adolescents and parents; Symptom Checklist-90-Revised rated by mothers and
      fathers. RESULTS: There were no group differences in self-reported health or self
      esteem. Parents reported more behavioural problems and lower psychosocial health
      for very-low-birthweight adolescents (p<0.001) compared with controls. Results
      did not differ significantly between small-for-gestational-age and control
      adolescents. The youngsters, their mothers and fathers perceived the same amount
      of relational warmth in all three groups. Very-low-birthweight parents reported
      more emotional impact than control parents, especially in the presence of
      psychiatric problems and cerebral palsy. There were no group differences in
      mothers' or fathers' mental health. CONCLUSION: The low-birthweight adolescents
      perceived quality of life as others did, but the parents reported functional
      disadvantages for the very-low-birthweight group. Birthweight did not influence
      the warmth in the parent-child relationship. Parents of very-low-birthweight
      adolescents experienced increased emotional burden, but they did not have more
      mental health problems than others.

PMID- 16278997
TI  - Breastfeeding patterns, beliefs and attitudes among Kurdish mothers in
      Diyarbakir, Turkey.
AB  - AIM: The aim was to rapidly assess existing breastfeeding patterns, beliefs and
      attitudes in the province of Diyarbakir, a socio-economically disadvantaged
      region of Turkey. METHODS: A cross-sectional survey exploring demographic and
      breastfeeding patterns was carried out among 921 mothers with children 6-18 mo of
      age. Results were quantitatively analysed. Focus group interviews dealing with
      beliefs and attitudes were separately carried out among 107 mothers and analysed
      by qualitative content analysis. RESULTS: Nearly all mothers had breastfed their
      infants at some time, but exclusive breastfeeding was rare. About 62.2% of the
      mothers had waited for at least 24 h before initiating breastfeeding. Almost half
      of the infants received sweetened water as a first feeding. There was agreement
      on the superiority of breastfeeding and awareness of its contraceptive effect.
      Early introduction of sugared water, water and supplementary feeds was considered
      desirable. Working in the fields and pregnancy were considered situations
      counteracting breastfeeding. CONCLUSION: The attitude to breastfeeding was highly
      positive, but more information is needed to encourage the use of colostrum,
      discourage early supplementation and promote exclusive breastfeeding during the
      first 6 mo of life.

PMID- 16278998
TI  - Socio-economic determinants, maternal smoking and coffee consumption, and
      exclusive breastfeeding in 10205 children.
AB  - AIM: To examine socio-economic factors, smoking, coffee consumption and exclusive
      breastfeeding duration. METHODS: This study was part of a prospective cohort
      study of children born between 1 October 1997 and 1 October 1999 (the All Babies
      in Southeast Sweden (ABIS) study). Eleven socio-economic characteristics
      (parental employment, civil status, whether parents were born in Sweden, parental
      education, residence at birth and during child's first year, crowded living),
      maternal smoking, coffee consumption, infant sex, siblings, parental age, and
      maternal alcohol consumption during pregnancy were analysed using logistic
      regression and Cox's proportional hazards method. All data were obtained through
      questionnaires distributed at infant birth and at 1 y of age. Exclusive
      breastfeeding duration<4 mo and actual breastfeeding duration were our main
      outcome measures. RESULTS: Out of 10205 infants, 2206 (21.6%) were exclusively
      breastfed for less than 4 mo ("short exclusive breastfeeding"; SEBF). Backward
      stepwise regression analysis identified the following risk factors for SEBF:
      maternal smoking (95% confidence interval for adjusted odds ratio, 95% CI AOR
      2.00-2.82), low maternal education (95% CI AOR 1.45-2.19), maternal employment
      less than 3 mo during pregnancy (95% CI AOR 1.17-1.54), paternal age<or=29 y (95%
      CI AOR 1.14-1.47), maternal age<or=29 y (95% CI AOR 1.08-1.39) and low paternal
      education (95% CI AOR 1.08-1.48). The odds ratio for SEBF increased with the
      number of cigarettes smoked. Coffee consumption was not associated with duration
      of exclusive breastfeeding. CONCLUSION: This study indicates that socio-economic
      factors and smoking may be of importance to the risk of breastfeeding exclusively
      for less than 4 mo, while coffee consumption is not.

PMID- 16278999
TI  - Gender affects self-evaluation in children with cystic fibrosis and their healthy
      siblings.
AB  - AIM: To determine whether self-esteem among children with cystic fibrosis (CF)
      and their healthy siblings differs from that of a healthy reference group and
      whether there are differences within and between sibling pairs. METHODS: All
      Swedish CF children 6-14 y old with a healthy sibling in the same age range
      (n=65) were invited to participate, 55 sibling pairs and their parents taking
      part in the study. Five aspects of the children's self-concept-physical
      characteristics, skills and talents, mental well-being, relations to parents and
      family, and relations to others-were assessed by the "I think I am" self
      evaluation questionnaire. Severity of illness was assessed by means of the
      Shwachman Clinical Evaluation System. RESULTS: Whereas self-evaluation did not
      differ between groups at a general level, healthy girls as well as those with CF
      scored lower than girls in the reference group on the "mental well-being" and
      "relations to parents and family" subscales. Comparison of gender combinations
      (sick girl/healthy boy, sick girl/healthy girl, sick boy/healthy boy, sick
      boy/healthy girl) suggested that girls pay a cost of a lesser sense of
      psychological well-being and feelings of inadequacy in relation to their parents
      and family. The Shwachman score of the sick child was not related to the level of
      self-esteem. CONCLUSION: When CF is present among siblings, girls seem to carry
      more of the family pain than boys, a finding that calls for an increased
      awareness of the girls' situation by members of care teams.

PMID- 16279000
TI  - Ages and Stages Questionnaire used to measure cognitive deficit in children born
      extremely preterm.
AB  - AIM: To validate the Ages and Stages Questionnaire (ASQ) and to measure average
      cognitive deficit in children born extremely preterm. METHODS: Parents of 30 term
      children aged 36-42 mo completed the ASQ and the children underwent the Wechsler
      Preschool and Primary Scales of Intelligence--Revised. In a second study, the ASQ
      was obtained in 22 children born extremely preterm and 19 term children at the
      age of 35-44 mo. RESULTS: The overall ASQ score correlated significantly with IQ
      (p=0.007). The children born extremely preterm had an ASQ score of -1.06 SD below
      the score of the term children (p=0.048). CONCLUSION: The ASQ identified a
      developmental deficit of the expected magnitude.

PMID- 16279001
TI  - Neurodevelopmental outcome and haematological course of a long-time survivor with
      homozygous alpha-thalassaemia: case report and review of the literature.
AB  - AIM: Homozygous alpha-thalassaemia, also called haemoglobin (Hb) Bart's hydrops
      fetalis, has been thought to be a lethal condition. Due to prenatal diagnosis and
      intrauterine blood transfusions, a few patients with Hb Bart's hydrops fetalis
      have survived. This fact raises the urgent questions of clinical management and
      appropriate follow-up of these patients, both of which are addressed in this
      article. METHODS: We report on a 6.5-y-old patient with homozygous alpha
      thalassaemia and review the literature of 13 other survivors published to date.
      Transfusion requirements were evaluated and the rate of liver iron accumulation
      was assessed by biomagnetic liver susceptometry before and after institution of
      iron-chelating therapy. Psychometric evaluation was carried out using Munich's
      Functional Development Test, the Columbia Mental Maturity Scale, the Kaufman
      Assessment Battery for Children, and the Peabody Picture Vocabulary Test.
      RESULTS: Our patient had significant delay of psychomotor development.
      Psychometric evaluation at the age of 5 y revealed an IQ of 85 and an
      intellectual level of a 4-y-old child. Early tissue iron overload was seen, but a
      negative iron balance was achieved after institution of desferrioxamine treatment
      at dosages used for beta-thalassaemia. CONCLUSION: Homozygous alpha-thalassaemia
      should no longer be regarded as a lethal condition. Early intervention during
      pregnancy and careful haematological as well as neuropsychological follow-up was
      able to provide long-term survival and good life quality in our patient.

PMID- 16279002
TI  - Long-term follow-up of a girl with primary aldosteronism: effect of potassium
      supplement.
AB  - We followed up a girl with primary aldosteronism for 8 y, which was diagnosed at
      6 y of age when she was referred to us for evaluation of heart murmur and growth
      failure. The diagnosis of bilateral adrenal hyperplasia was made by selective
      adrenal venous sampling. Following potassium supplement, her retarded growth was
      corrected dramatically, and she attained a normal adult height. Puberty developed
      normally and menarche occurred at 12 y of age. Blood pressure was also controlled
      adequately. Myocardial hypertrophy associated with aortic damage was noted at 13
      y of age. Chronic renal failure developed with proteinuria and enlarged renal
      cysts. CONCLUSION: Serum electrolytes should be included in the evaluation of
      children with impaired growth. Although primary aldosteronism is a rare
      occurrence in children, the condition appears to deserve special attention not
      only from the viewpoint of growth failure and hypokalaemia but from the
      occurrence of late organ damage to the kidney and heart.

PMID- 16279003
TI  - Acute severe spinal cord dysfunction in a child with meningitis: Streptococcus
      pneumoniae and Mycoplasma pneumoniae co-infection.
AB  - Tetraplegia developed abruptly in an 11-y-old with pneumococcal meningitis.
      Magnetic resonance imaging showed multiple hyperintensities at the brainstem
      spinal cord junction. Serological tests were positive for Mycoplasma pneumoniae
      (microparticle agglutination and specific IgMs). Erythromycin and dexamethasone
      were started promptly, and 10 d later the patient was discharged with normal
      neurological function. CONCLUSION: Tetraplegia during the course of pneumococcal
      meningitis in an 11-y-old girl disappeared after treatment with ceftriaxone,
      erythromycin and dexamethasone.

PMID- 16279005
TI  - Serum amyloid A (SAA) protein and high-sensitivity C-reactive protein (hsCRP) in
      healthy newborn infants and healthy young through elderly adults.
AB  - AIM: To determine the levels of serum amyloid A (SAA) protein and high
      sensitivity C-reactive protein (hsCRP) in different age groups. METHODS: Serum
      samples from 70 healthy newborn infants, 80 blood donors and 81 healthy elderly
      individuals were analysed using a nephelometric method. The 231 samples were
      grouped as follows: 35 umbilical cords, 35 newborns, 48 young adults, 28 middle
      aged adults, and 85 elderly adults. RESULTS: Serum levels of both SAA and hsCRP
      were lower in umbilical cords than in the newborns and young, middle-aged and
      elderly adults (p<0.0001). The SAA and hsCRP levels were comparable in newborns,
      and young and middle-age adults, but higher in elderly adults (p<0.0001-0.03).
      SAA (r2=0.159, p<0.0001) and hsCRP (r2=0.059, p<0.0001) were positively
      correlated with age and to each other (r2=0.385, p<0.0001). CONCLUSION: Serum
      levels of SAA and hsCRP in umbilical cord blood are close to the detection limit
      and lower than in the other age groups investigated. The elderly have generally
      higher levels than the younger age groups, which require higher decision levels
      in inflammatory diseases, including infections. In newborns and young and middle
      aged adults, the lower decision levels of 10 mg/l for SAA and 5 mg/l for CRP are
      suggested.

PMID- 16279004
TI  - Cervicofacial nocardiosis in an immunocompetent child.
AB  - Nocardiosis occurs primarily as an opportunistic infection in an
      immunocompromised host. The infection may on rare occasion occur in a normal host
      confounding the diagnosis. It is also notably an uncommon infection in children.
      We report a 1-y-old girl with cervicofacial nocardial infection who presented
      with acute suppurative otitis media and lymphadenitis. This child did not have
      any predisposing risk factors for this infection and responded well to treatment
      with co-trimoxazole and chloramphenicol. She is doing well on follow-up.
      CONCLUSION: Nocardiosis in an immunocompetent small child is reported.

PMID- 16279006
TI  - [Results of 46 digital replantations. With a minimal follow-up of one year].
AB  - Forty six digital replantations were analysed with a minimum follow-up of one
      year. The mechanism of the injury and the level of the amputation were
      systematically analysed to asses the objective (mobility, sensitivity,
      prehension), and the subjective results (pain, vasomotor dysfunction,
      satisfaction). The replantations were typically in the long fingers in young men
      (index and middle fingers at the level of the middle phalanx) by work or
      industrial accident (complete section or digital crushing). Seventeen
      replantations (37%) were secondarily amputated. Arterial thrombosis was the main
      cause of amputation in 94% of the cases and had occurred in 50% of the cases by
      the forty eight postoperative hour. An early revascularization procedure was
      attempted in ten cases (21%). Among these ten revascularizations procedures, we
      noted eight failures (80%). During the first six postoperative weeks, the
      complications of the replantations were skeletal displacements, tendon ruptures
      and joint subluxations. After six weeks, the complications were joint stiffness
      (26%), sensory deficits (19.5%), severe cold intolerance (13%), vasomotor
      dysfunction (10%) with stiffness of the proximal interphalangeal joints in 60% of
      the cases. We noted other complications such as neuroma of distal stump,
      cutaneous retraction and deformation of the fingers. Finally, only nine digital
      replantations (19.5%) evolved favourably with complete restoration of
      sensorimotor function without any complication. The best results were obtained
      from amputations of the middle finger with the mechanism of section being a
      circular saw (40%).

PMID- 16279007
TI  - [Some problems on the organ transplantation in Japan from the viewpoint of the
      neurocritical care units].
AB  - The authors have referred to several issues encountered in the neuroemergency and
      critical care facilities in our country through the declaration of brain death to
      the successful removal of organs for donation. One of the most important is the
      fact that the legal validity of death in brain dead patients is only assured when
      the patient shows the advance directive for organ donation in Japan. So far as
      the selection of the recipient is not started until the brain death is declared
      legally, longer than 12 hours are to be spent in vain between the declaration of
      brain death and the beginning of the operation of removing the organs for
      donation. As there remain such several problems to be solved as mentioned above
      for organ donation in Japan, so it is suggested that the medical sciences and
      ethics should be respected and adopted in the rules for the organ donations by
      the national government.

PMID- 16279008
TI  - Medicare program; home health prospective payment system rate update for calendar
      year 2006. Final rule.
AB  - This final rule sets forth an update to the 60-day national episode rates and the
      national per-visit amounts under the Medicare prospective payment system for home
      health agencies. This final rule is the first update of the home health
      prospective payment system (HH PPS) rates that uses the revised area labor market
      Metropolitan Statistical Area designations for calendar year 2006. In
      implementing the new area labor market designations, we are allowing for a one
      year transition period. This transition consists of a blend of 50 percent of the
      new area labor market designations' wage index and 50 percent of the previous
      area labor market designations' wage index. In addition, we are revising the
      fixed dollar loss ratio, which is used in the calculation of outlier payments.

PMID- 16279009
TI  - [Tacrolimus (FK506) in refractory ulcerative colitis: an alternative to
      proctocolectomy?].

PMID- 16279010
TI  - Adsorption of lanthanoid ions on calcite.
AB  - The adsorption of 14 trivalent lanthanoid ions and yttrium ion (denoted by Ln3+)
      on calcite surfaces was investigated under various solution conditions of pH (pH
      = 6.8-7.8) and calcium ion concentration (pCa = -log[Ca2+]= 2.0 and 3.0), and
      different surface conditions of calcite crystals (well-developed and rough
      surfaces). The lanthanoid ions were equilibrated in a solution of ionic strength
      0.1 mol dm-3(NaCl) saturated with calcite at 25.0 degrees C using excess (solid)
      calcite crystals suspended in solution. The concentrations of the lanthanoid ions
      on the calcite crystals (C(cry)/mol kg-1) and in solution (C(soln)/mol dm-3) were
      determined by means of inductively coupled plasma-mass spectrometry (ICP-MS). It
      is found that the distribution ratio (D=C(cry)/C(soln) decreases as the atomic
      number of the lanthanoid increases showing the so called Tetrad Effect. D values
      increase with increasing pH, whereas they are independent of the calcium ion
      concentration (i.e., carbonate ion concentration). These results indicate that
      lanthanoid ions are adsorbed on the calcite surface together with hydroxide ions,
      i.e., the adsorption of hydroxo-complexes. The heavy lanthanoid ions (Er3+ to
      Lu3+) are adsorbed as monohydroxo-complexes, (Ln(OH)2+), whereas those of the
      light lanthanoids are predominantly adsorbed as dihydroxo-complexes (Ln(OH)2+).
      Other lanthanoids show competitive adsorption reactions of mono- and dihydroxo
      complexes. Both successive adsorption constants of hydroxo complexes increase
      with decreasing atomic number of the lanthanoid. The rough surface of calcite is
      quite active and the distribution ratio of the lanthanoid ions on the rough
      surface is much higher than that on the well-developed crystalline surface. Rates
      of adsorption of lanthanide ions were measured and mechanisms are being discussed

PMID- 16279011
TI  - Validation of the Portuguese version of the Asthma Quality of Life Questionnaire
      [AQLQ-M] by Marks.
AB  - Quality of Life is one of the leading evaluations in the diagnosis, therapy and
      investigation of patients with asthma. The aim of this study was to evaluate the
      psychometric properties of the Portuguese version of the Asthma Quality of Life
      Questionnaire (AQLQ-M) designed by Marks in Australia. This questionnaire
      consists of 20 items describing the impact of asthma on patient's lifestyle and
      covers 4 dimensions (breathlessness, mood, social limitation and worrying). After
      a process of translation, backtranslation, and pretest, the Portuguese version of
      AQLQ-M was administered to 82 adults asthmatics living in 3 different urban
      areas. The following data were also recorded: age, sex, main symptoms, duration
      of disease, hospital visits, severity of disease, and medication. All patients
      performed spirometry. The reliability study (internal consistency with Cronbach's
      alpha coefficient and inter-item correlation analysis) gave satisfactory results
      (range of r= 0.58 to 0.94; a= 0.91 to 0.97). Results for construct validity shown
      that the breathlessness dimension presented the largest numbers of significant
      correlations with the most important clinical variables of asthma. In conclusion,
      this study has shown that the Portuguese version of the AQLQ-M has good
      psychometric properties, and is suitable for use on individual patients with
      asthma in our country.

PMID- 16279012
TI  - [TIPS or paracentesis for refractory ascites in cirrhosis?].

PMID- 16279013
TI  - [The risk of pancreatic surgery].

PMID- 16279014
TI  - [DNA chip technology applied to pancreatic carcinoma].

PMID- 16279015
TI  - [Virtual colonoscopy with 'virtual' bowel cleansing? More questions than answers
      ...].

PMID- 16279016
TI  - [Relationship between serum calcium level and PTH concentration proved with
      sevelamer hydrochloride].
AB  - About a dialysis patient's calcium-phosphate (Ca.P) metabolism, in general good
      control is obtained by use of sevelamer hydrochloride. As for this, what is
      significantly depended on not only lower P concentration but also lower Ca
      concentration by the change to sevelamer hydrochloride from calcium carbonate.
      However, by one side, much rises of i-PTH are observed by most patients with
      change to sevelamer hydrochloride. In this examination, Deltai-PTH was
      intentionally correlated with Delta calcium concentration but there was no
      correlation in i-PTH and Ca concentration.

PMID- 16279017
TI  - [Effect of calcium on N-terminal truncation of PTH in human parathyroid cells].
AB  - Serum PTH (7-84) is accumulated in patients with secondary hyperparathyroidism.
      It is also known that serum calcium (Ca) increases the generation of N-terminally
      truncated forms of parathyroid hormone (PTH). In this study, we examined whether
      accumulation of PTH (7-84) fraction is a parathyroid glandular origin or not by
      using primary cultured parathyroid cells from patients with primary and secondary
      hyperparathyroidism. The Bio-PTH/I-PTH ratio, indicating the ratio of PTH (1-84)
      to the sum of (1-84) PTH and N-terminally truncated fragment, was suppressed by
      increase in extracellular Ca2+ concentration for both cultured parathyroid cells
      prepared from parathyroid adenomas and uremia-associated secondary
      hyperparathyroidism. There is no difference between the ratios in primary and
      secondary hyperparathyroidism. These findings suggest that N-terminal truncation
      is regulated by extracellular Ca2+ concentration in parathyroid cells, but
      accumulation of PTH (7-84) fragments in patients with secondary
      hyperparathyroidism is mainly caused by uremia.

PMID- 16279018
TI  - [Significance of serum PTH (7-84) as a reliable nutritional marker in
      hemodialysis patients].
AB  - To evaluate the significance of serum PTH (7-84) in hemodialysis patients,
      correlation of the serum PTH (7-84) level with various nutritional markers was
      investigated in HD patients. Serum PTH was determined in 170 male HD patients by
      either a Bio intact PTH assay or a second-generation intact PTH assay. The level
      of bone formation markers and bone resorption markers were also measured. Lean
      body mass in trunk region was measured by dual X-ray absorptiometry. The serum
      PTH (7-84) level was obtained for the difference between serum I-PTH and Bio-PTH.
      Serum PTH (1-84) was directly obtained from the serum Bio-PTH value. Serum PTH (7
      84) correlated significantly with nutritional markers such as body weight,
      albumin, PCR, TAC BUN, BUN, phosphate and lean body mass in trunk, whereas PTH (1
      84) only correlated with phosphate. The correlation of serum PTH (7-84) with bone
      metabolic markers was no less significant than that for PTH (1-84). The results
      suggest that serum level of PTH (7-84) may provide clinically useful information,
      not only of the bone metabolic state but also of the nutritional state in HD
      patients, in sharp contrast to the exclusive correlation of PTH (1-84) with bone
      metabolic state.

PMID- 16279019
TI  - [Vascular calcification in advanced secondary hyperparathyroidism].
AB  - Cardiovascular disease is one of the largest cause of mortality in maintenance
      hemodialysis patients. Vascular calcifications frequently encountered in
      hemodialysis patients. In advanced uremic secondary hyperparathyroidism model
      mice, vascular calcifications were observed in their aorta, by Kossa staining.
      This mouse model may be a useful model to study vascular calcification in
      maintenance hemodialysis patients.

PMID- 16279020
TI  - [Low dose estrogen replacement therapy (ERT) for postmenopausal hemodialysis (HD)
      patients].
AB  - We studied the short-time effects of low dose estradiol (E2) on bone metabolism
      in hemodialysis (HD) patients. We prescribed transdermal E2 (0.36 mg every other
      day) to 17 non-diabetic postmenopausal osteoporotic HD patients and measured
      intact parathyroid hormone (iPTH), serum NTX (sNTX), intact osteocalcin (iOC),
      and bone resorptive cytokines including IL-6 and TNF-alpha. Serum E2 increased
      from 20 to approximately 40 pg/mL, which is comparable to that of male HD
      patients. Three-month treatment decreased serum calcium by 0.7 mg/dL followed by
      a significant elevation of iPTH and iOC. Despite the increase of iPTH, collagen
      breakdown product, sNTX did not change significantly, implying decreased skeletal
      sensitivity to PTH resorbing effect. IL-6 and TNF-alpha decreased, but this trend
      was not statistically significant. Bone pain and/or pain from carpal tunnel
      syndrome resolved by ERT. We needed to dose-up active vitamin D to control
      enhanced iPTH. Our data suggests that E2 attenuates the resorbing effect of PTH
      and stimulates bone formation, also in HD patients.

PMID- 16279021
TI  - [Clinical effect of introduction of sevelamer hydrochloride in patients with
      hyperphosphatemia undergoing maintenance dialysis].

PMID- 16279022
TI  - [Sevelamer hydrochloride and K/DOQI guidelines].

PMID- 16279023
TI  - [Parathyroid gland intervention therapy for patients with secondary
      hyperparathyroidism due to dialysis].

PMID- 16279024
TI  - [Sevelamer hydrochloride and vitamin D for controlling serum calcium, phosphorus
      and bone metabolism in patients undergoing hemodialysis].

PMID- 16279025
TI  - [Role of sevelamer hydrochloride in the Coronary Artery Calcification Index].

PMID- 16279026
TI  - [Cell proliferation of parathyroid gland in patients with progressive secondary
      hyperparathyroidism: Vitamin D receptor, calcium sensing receptor, and cell cycle
      regulation factor].

PMID- 16279027
TI  - [Management of secondary hyperparathyroidism].

PMID- 16279028
TI  - [Present status and problems in vitamin D and sevelamer therapy (discussion)].

PMID- 16279030
TI  - Advances in the treatment of heart failure.

PMID- 16279029
TI  - Your duty to noncompliant patients.

PMID- 16279031
TI  - [Dilated cardiomyopathy and heart failure].

PMID- 16279032
TI  - [Endothelial dysfunction and its clinical impact on patients with chronic
      obstructive lung disease].

PMID- 16279033
TI  - [Gastroesophageal reflux disease: pathogenesis, clinical manifestation,
      diagnostics, and treatment].

PMID- 16279034
TI  - [Hyperhomocysteinemia in patients with cerebral stroke].
AB  - Moderate hyperhomocysteinemia often accompanies cerebral strokes. The aim of this
      study was to evaluate serum levels of homocysteine in patients with stroke, and
      its dependence on stroke type, the patient's age and gender, presence or absence
      of arterial hypertension (AH) background, and cholesterol level. The subjects
      were 71 patients and 23 healthy adults. The results demonstrate a significant
      elevation of homocysteine concentration in the stroke patient vs. the healthy
      subjects, and its dependence on gender, AH background, repeated strokes, and
      cholesterol level (p < 0.05).

PMID- 16279035
TI  - [Diagnostics of diabetes mellitus in the acute period of myocardial infarction].
AB  - The purpose of the study was to measure glycosylated hemoglobin (HbA1c) level in
      patients with hyperglycemia during the acute period of myocardial infarction
      (MI). The authors performed retrospective evaluation of glycemia level within a
      period of 90 to 120 previous days. The study revealed that measurement of this
      parameter during first 1 to 3 days of MI allows, firstly, primary diagnostics of
      type II diabetes which occurred at least 3 months before the MI, and, secondly,
      confirmation of the already existing diagnosis of concomitant diabetes,
      evaluation of the degree of its compensation before the occurrence of the MI and
      the effectiveness of the antidiabetic treatment. The results of such testing
      allow timely and adequate glucose-regulating therapy, lowering of diabetes hyper
      diagnostics, and thus, improvement of therapeutic tactics.

PMID- 16279036
TI  - [Absorptional function of the small bowel in patients with chronic obstructive
      bronchitis].
AB  - The purpose of the study was to evaluate intestinal absorption of fats, proteins
      and carbohydrates in patients with chronic obstructive bronchitis (COB) depending
      on the functional condition of the lungs, and clinical manifestation of its
      disorder. Fat, protein and carbohydrate absorption was studied in 68 COB
      patients. Lung ventilation was evaluated by means of spirography, pulmonary gas
      exchange--via measurement of paO2 of arterialized capillary blood by Astrup
      method. Fat absorption was evaluated using Kamer method and radioindication with
      131I-trioleate-glycerine and 131I-oleic acid; protein absorption was determined
      using 131I-albumin; carbohydrate absorption was determined by d-xylose test. The
      study demonstrated that deterioration of respiratory and ventilatory pulmonary
      functions in patients with COB impaired fat, protein and carbohydrate absorption:
      paO2 > or = 70 mmHg and ventilatory insufficiency (VI) I were associated with an
      significant reduction of fat absorption by 49% on the average, protein--by 23%,
      carbohydrates--by 15%; paO2 = 70-40 mmHg and VI II-III--with reduction of these
      parameters by 104%, 69%, and 41%, respectively. The results show a direct
      correlation between body weight (BW) deficit and the reduction of fat, protein,
      and carbohydrate absorption (r = 0.549, 0.707, and 0.482, respectively) in COB
      patients. The most prominent was the correlation between BW deficit and the
      reduction of protein absorption. Thus the study of intestinal absorption of fats,
      proteins and carbohydrates in patients with COB demonstrates not only reduction
      of absorption, correlating with the degree of the impairment of ventilatory and
      respiratory pulmonary functions, but also direct correlations between BW deficit
      and reduction of fat, protein and carbohydrate absorption.

PMID- 16279037
TI  - [Melanin-producing and NO-synthase gastric cells and the processes of cell
      regeneration in gastric and duodenal ulcers].
AB  - The subjects of the study were 50 patients with gastric ulcer, 110 patients with
      duodenal ulcer, 70 patients with chronic Helicobacter-associated gastritis, and
      60 practically healthy individuals. Diagnosis was based upon the results of
      clinical, instrumental, and morphological examination. The results of the study
      show thatfunctional activity of gastric epitheliocytes and apudocytes,
      manifesting in decrease or increase of certain hormone activity, correlates with
      the process of apoptosis, which leads either to activation of ulcerogenesis, or
      to healing of a peptic ulcer. The study established the role of NO-positive
      melatonin epitheliocytes in peptic ulcer development.

PMID- 16279038
TI  - [Immediate and long-term effects of endoscopic papillosphincterotomy in patients
      with cholelithiasis].
AB  - The subjects of the study were 164 patients, divided into two groups. Group I
      included 76 patients at the physicochemical stage of cholelithiasis, and 38
      patients after cholecystectomy, who underwent endoscopic papillosphincterotomy
      (EPST). Group II (control) included 30 patients at the physicochemical stage of
      cholelithiasis, and 20 patients after cholecystectomy, who did not undergo EPST.
      Endoscopic retrograde pancreatocholangiography revealed type II Oddi's sphincter
      dysfunction in all the patients. Evaluation of the chemical composition of bile
      in Group I, performed 6, 12, 18, and 24 months after EPST, revealed its graduate
      stabilization. In Group II the dynamics of bile composition was negative--in 8
      patients bile became more lithogenic. Long-term observations showed that 6 years
      after EPST bile was lithogenic only in 4 Group I patients, while at the same
      moment in 25 Group I patients bile lithogenicity did not disappear, but even
      worsened. Biliferous tract ultrasonography, performed long after EPST, found
      biliary sludge in 4 Group I patients. 6-year observation of Group Il patients,
      including ultrasonography, demonstrated that during the 4th year of observation
      biliary sludge occurred in as many as 28 patients, in 15 of whom small
      concrements on the bottom of the gall bladder were found during the 5-6th year of
      observation, and in 3 of whom a solitary concrement of 4 to 5 mm in diameter was
      found in the choledoch. The results demonstrate that it is appropriate to perform
      EPST as early as at the physicochemical stage of cholelithiasis, because this
      procedure results in stabilization of biliary colloid balance and thus prevents
      biliary sludge and forming of gall bladder concrements. At the same time, 36% of
      patients with cholelithiasis at various stages who did not undergo EPST, formed
      gall bladder concrements. EPST is also appropriate in some patients after
      cholecystectomy, in order to prevent repeating gall bladder concrement formation.

PMID- 16279039
TI  - [Immunoregulatory cytokines and chronization of type C hepatitis: matching of
      clinical and immunological manifestations].
AB  - The study demonstrates significant changes of cytokine-producing ability of
      mononuclear blood leucocytes in type 'hepatitis, correlating with the degree of
      hepatic lesion. The results showed that various morphologic types of chronic
      virus type C hepatitis were associated with disbalance in production of pro- and
      antiinflammatory cytokines, i.e. decrease of tumor necrosis factor (TNF)-alpha
      concentration and a significant rise of interleukin (IL)-4 and IL-10
      concentations, which were the most prominent in cases of severe hepatic fibrosis
      and high histologic activity of hepatitis. The study established a direct
      correlation between increase of the ability of mononuclear blood leucocytes to
      synthesize IL-4, and the progress of the pathologic process.

PMID- 16279040
TI  - [Use of fragmin in program hemodialysis of patients with terminal chronic renal
      failure].
AB  - The subjects of the study were 60 patients at the end stage of chronic renal
      failure of various origins, who were on program hemodialysis (PHD) in Dialysis
      Center of City hospital #20. The main group consisted of 25 patients, who were
      administered fragmin (Pfizer, USA), a low-molecular heparin, for hypocoagulation
      during the procedure of hemodialysis. The drug was administered in a bolus dose
      of 5000 aXa ICU into the arterial line after connecting it to a fistula needle.
      The control group (35 patients) received unfranctionated heparin (UFH) in a
      conventional way (a bolus of 2000 to 2500 IU before the beginning of the
      procedure, followed by 1200 to 1500 IU/h in a continuous infusion, stopped 1 hour
      prior to the end of the dialysis). The following parameters were measured at the
      beginning and the end of the procedure: the number of thrombocytes, hemoglobin
      and hematocrit levels, activated partial thromboplastin time, activated
      coagulation time, antithrombin III level, and anti-Xa factor activity. Standard
      regimen of UFH administration allowed satisfactory hypocoagulation, but the
      necessary dose was hard to select. A bolus dose of fragmin led to adequate
      hypocoagulation in all the patients: there were no fibrin or blood clots in the
      lines or the dialyzer, or hemorrhage from the sites of puncture after the
      procedure. Anti-Xa-factor activity grew after a bolus injection of fragmin. By
      the end of the procedure the inhibitory activity of fragmin towards Xa-factor
      remained at the level of 0.44 +/- 0.7 IU/ml. The results show that a single dose
      of fragmin is effective and safe during a standard procedure of hemodialysis
      lasting up to 5 hours.

PMID- 16279041
TI  - [Use of the ACE inhibitor perindopril in patients with chronic obstructive lung
      diseases, complicated by cor pulmonale].
AB  - The purpose of the study was to evaluate hemodynamic effects and safety of the
      ACE inhibitor perindopril in treatment of secondary pulmonary hypertension (PH)
      in patients with chronic obstructive bronchitis (COB). The subjects were 42
      patients with COB and secondary PH (functional class (FC) III-IV), whose
      treatment included 4-week administration of perindopril. Studied were hemodynamic
      parameters and day profile of blood pressure (24-hour monitoring). Treatment of
      these patients with perindopril resulted in improvement of PH, positive changes
      in the right heart, and normalization of blood pressure day profile. Both course
      treatment and prolonged administration of perindopril were effective in COB
      patients with clinical manifestations of FC III and IV PH. Long outpatient
      administration of perindopril in individual doses led to good clinical results
      and significant positive hemodynamic changes. According to the authors, the ACE
      inhibitor perindopril may be recommended for correction of hemodynamic
      disturbances in cases of chronic cor pulmonale in patients with chronic
      obstructive lung diseases.

PMID- 16279042
TI  - [Efficacy of isosorbide-5-mononitrate retard in patients with stable exertional
      angina].
AB  - The aim of the study was to evaluate efficiency of isosorbide-5-mononitrate (IMN)
      retard (40 to 80 mg/day) in 33 patients older than 60 with stable angina pectoris
      (functional class III-IV). The study shows that IMN is an effective and safe
      antianginal agent in treatment of patients with stable angina: it decreased the
      frequency of anginal attacks (from 4.1 +/- 0.34 to 0.8 +/- 0.13 per day, p <
      0.0001), and additional nitroglycerin intake (from 2.2 +/- 0.32 to 0.2 +/- 0.05
      tablets per day, p < 0.0001); according to the results of 24-hour ECG monitoring,
      it reduced ST-segment depression (from 2.2 +/- 0.17 to 0.9 +/- 0.09, p < 0.0001),
      preventing episodes of painful and silent myocardial ischemia (from 3.5 +/- 0.37
      to 2.1 +/- 0.31, p < 0.0001); increased life quality as demonstrated by
      evaluation of physical (from 19.7 +/- 2.2 to 45.7 +/- 2.22, p < 0.0001), and
      mental (from 30.9 +/- 2.67 to 57.5 +/- 2.67, p < 0.0001) components using MOS-SF
      36 questionnaire. Adverse effects of the drug (headache and hypotension) were
      observed in 6 (16.6%) patients.

PMID- 16279043
TI  - [Indicators of heart failure functional classes at the stage of sanatorium
      rehabilitation of patients with myocardial infarction].
AB  - Heart failure (HF) is one of the most frequent consequences of acute myocardial
      infarction (AMI). The purpose of the study was to establish the most informative
      indicators of HF functional classes at the stage of sanatorium rehabilitation of
      Ml patients. The subjects were 509 Ml patients aged 56.1 +/- 0.5 years,
      undergoing rehabilitation in Saint Petersburg sanatorium Repino. Most of the
      patients (69%) were male. 433 patients (84.9%) had HF: 222 (51.2%)--functional
      class (FC) I HF, 166 (38.3%)--FC II HF, 23 (5.3%)--FC III HF, 22 (5%)--FC IV HF.
      The study established several informative indicators that allow a doctor to
      determine the FC of HF, such as left ventricle measurements; contraction
      fraction, determined by means of EchoCG; physical exercise tolerance, determined
      by means of veloergometry; decrease of working capacity, determined by means of
      24-hour ECG monitoring; distance walked by patients during 6-minute walking test.

PMID- 16279044
TI  - [A case of rupture of aneurysm of noncoronary sinus of Valsalva].

PMID- 16279045
TI  - [A rare case of generalized echinococcosis].

PMID- 16279046
TI  - [Primary small bowel lymphangioectasis].

PMID- 16279047
TI  - [Disputable aspects of acid-suppressive therapy].

PMID- 16279048
TI  - [The past, present, and future of semiotics and diagnostics].

PMID- 16279049
TI  - The anatomy of a national meeting or where is my crystal ball?

PMID- 16279050
TI  - Medium-chain acyl-CoA dehydrogenase deficiency: a case presentation.
AB  - When an infant presents with hypoglycemia, acidosis, hepatomegaly, and
      respiratory arrest, the neonatal team must be alert to the possibility of a
      metabolic disorder. Among those to be considered is medium-chain acyl-CoA
      dehydrogenase deficiency, which occurs in 1 in 10,000-23,000 live births.
      Recognizing and treating this disorder early could decrease the morbidity and
      mortality associated with the diagnosis.

PMID- 16279051
TI  - The neonatal respiratory pump: a developmental challenge with physiologic
      limitations.
AB  - Newborn lungs are particularly susceptible to pathophysiology. Respiratory
      distress commonly brings infants to the intensive care nursery. Premature birth
      compromises the infant's ability to respond to early lung dysfunction because of
      the reduced functional reserve available at younger gestational ages. The
      respiratory pump consists of respiratory musculature and the chest wall. The
      respiratory pump is the physiologic "machine" that responds to lung pathology.
      From gestation onward, components of the pump undergo developmental changes that
      influence its compensatory ability in the neonate. Careful observation of the
      synchrony of the chest wall and abdomen during spontaneous breathing efforts
      assists the caretaker in detecting respiratory compromise and impending
      respiratory failure. Noninvasive monitoring of respiratory patterns is a valuable
      tool for the neonatal caregiver, who must understand the developmental changes in
      the respiratory pump and be able to identify an infant's ineffective responses to
      lung pathophysiology.

PMID- 16279052
TI  - Myelomeningocele, avocados, and rubber tree plants.
AB  - Infants with myelomeningocele and the nurses who care for them have something in
      common. Both are at higher risk than the general population for developing latex
      allergies. This article provides a review of the literature regarding latex
      production, latex allergic responses in children and adults, types of latex
      allergic reactions, and prevention of latex allergies.

PMID- 16279053
TI  - Heparin-induced thrombocytopenia in neonates.
AB  - Heparin-induced thrombocytopenia (HIT), an immune-mediated response to heparin
      administration, has been recognized in adults for some time, but only recently
      recognized in neonates and children. HIT Type I is a mild, self-limiting
      condition. HIT type II is a severe immune reaction to heparin that leads to
      thrombocytopenia and often thromboembolic complications. The incidence of HIT
      Type II is 2-5 percent in adults on heparin products and may be as high in
      neonates and children. The mortality rate from HIT in adults is 7-30 percent and
      is unknown but potentially high in newborns as well. The cardinal sign of HIT is
      a drop in platelet count by 50 percent or platelet counts below 70,000
      100,000/mm3. This drop usually occurs five to ten days after the first exposure
      to heparin. Treatment is immediate cessation of all heparin therapy and
      initiation of alternative anticoagulants, especially the direct thrombin
      inhibitors lepirudin and argatroban. This article reviews the literature on HIT
      and presents a case of neonatal HIT following heart surgery.

PMID- 16279054
TI  - Newborn screening guidelines for the critically ill infant.
AB  - The use of mass spectrometry in newborn screening has made possible the early
      diagnosis of various metabolic diseases. However, because aminoglycosides, blood
      transfusions, nothing by mouth status, and the presence of heparinized solutions
      all affect the results of newborn screens, neonates in critical care units who
      receive such treatments ought to be screened under specific practice guidelines.
      Many of the devastating sequelae of metabolic diseases are preventable if
      diagnosed early, making the development of such practice guidelines for use in
      the NICU especially important. Additionally, no standardized practice guidelines
      presently exist for determining who, whether birth hospital or primary care
      provider, is responsible for notifying the parent of a positive result and thus
      ensuring invaluable follow-up care. Such standardized guidelines for screening
      practice are needed to prevent devastating neurologic sequelae for children whose
      condition may otherwise escape unaddressed. Newborn screening guidelines
      developed at Johns Hopkins Hospital and Memorial Regional Hospital provide a
      helpful starting point.

PMID- 16279055
TI  - Pneumothorax in the neonate: assessment and diagnosis.

PMID- 16279056
TI  - A day in the NICU: finding the strength to make a difference.

PMID- 16279057
TI  - Offering the physics exam to residents early in their residency is helpful to the
      residents and the radiology department. For the proposition.

PMID- 16279058
TI  - Offering the physics exam to residents early in their residency is helpful to the
      residents and the radiology department. Against the proposition.

PMID- 16279059
TI  - Segmented crystalline scintillators: an initial investigation of high quantum
      efficiency detectors for megavoltage x-ray imaging.
AB  - Electronic portal imaging devices (EPIDs) based on indirect detection, active
      matrix flat panel imagers (AMFPIs) have become the technology of choice for
      geometric verification of patient localization and dose delivery in external beam
      radiotherapy. However, current AMFPI EPIDs, which are based on powdered-phosphor
      screens, make use of only approximately 2% of the incident radiation, thus
      severely limiting their imaging performance as quantified by the detective
      quantum efficiency (DQE) (approximately 1%, compared to approximately 75% for
      kilovoltage AMFPIs). With the rapidly increasing adoption of image-guided
      techniques in virtually every aspect of radiotherapy, there exist strong
      incentives to develop high-DQE megavoltage x-ray imagers, capable of providing
      soft-tissue contrast at very low doses in megavoltage tomographic and,
      potentially, projection imaging. In this work we present a systematic theoretical
      and preliminary empirical evaluation of a promising, high-quantum-efficiency,
      megavoltage x-ray detector design based on a two-dimensional matrix of thick,
      optically isolated, crystalline scintillator elements. The detector is coupled
      with an indirect detection-based active matrix array, with the center-to-center
      spacing of the crystalline elements chosen to match the pitch of the underlying
      array pixels. Such a design enables the utilization of a significantly larger
      fraction of the incident radiation (up to 80% for a 6 MV beam), through increases
      in the thickness of the crystalline elements, without loss of spatial resolution
      due to the spread of optical photons. Radiation damage studies were performed on
      test samples of two candidate scintillator materials, CsI(Tl) and BGO, under
      conditions relevant to radiotherapy imaging. A detailed Monte Carlo-based study
      was performed in order to examine the signal, spatial spreading, and noise
      properties of the absorbed energy for several segmented detector configurations.
      Parameters studied included scintillator material, septal wall material, detector
      thickness, and the thickness of the septal walls. The results of the Monte Carlo
      simulations were used to estimate the upper limits of the modulation transfer
      function, noise power spectrum and the DQE for a select number of configurations.
      An exploratory, small-area prototype segmented detector was fabricated by
      infusing crystalline CsI(Tl) in a 2 mm thick tungsten matrix, and the signal
      response was measured under radiotherapy imaging conditions. Results from the
      radiation damage studies showed that both CsI(Tl) and BGO exhibited less than
      approximately 15% reduction in light output after 2500 cGy equivalent dose. The
      prototype CsI(Tl) segmented detector exhibited high uniformity, but a lower-than
      expected magnitude of signal response. Finally, results from Monte Carlo studies
      strongly indicate that high scintillator-fill-factor configurations,
      incorporating high-density scintillator and septal wall materials, could achieve
      up to 50 times higher DQE compared to current AMFPI EPIDs.

PMID- 16279061
TI  - Dose-response characteristics of an amorphous silicon EPID.
AB  - Electronic portal imaging devices (EPIDs) were originally developed for the
      purpose of patient setup verification. Nowadays, they are increasingly used as
      dosimeters (e.g., for IMRT verification and linac-specific QA). A prerequisite
      for any clinical dosimetric application is a detailed understanding of the
      detector's dose-response behavior. The aim of this study is to investigate the
      dosimetric properties of an amorphous silicon EPID (Elekta IVIEWGT) with respect
      to three photon beam qualities: 6, 10, and 25 MV. The EPID showed an excellent
      temporal stability on short term as well as on long term scales. The stability
      throughout the day was strongly influenced by warming up, which took several
      hours and affected EPID response by 2.5%. Ghosting effects increased the
      sensitivity of the EPID. They became more pronounced with decreasing time
      intervals between two exposures as well as with increasing dose. Due to ghosting,
      changes in pixel sensitivity amounted up to 16% (locally) for the 25 MV photon
      beam. It was observed that the response characteristics of our EPID depended on
      dose as well as on dose rate. Doubling the dose rate increased the EPID
      sensitivity by 1.5%. This behavior was successfully attributed to a dose per
      frame effect, i.e., a nonlinear relationship between the EPID signal and the dose
      which was delivered to the panel between two successive readouts. The sensitivity
      was found to vary up to 10% in the range of 1 to 1000 monitor units. This
      variation was governed by two independent effects. For low doses, the EPID signal
      was reduced due to the linac's changing dose rate during startup. Furthermore,
      the detector reading was influenced by intrabeam variations of EPID sensitivity,
      namely, an increase of detector response during uniform exposure. For the beam
      qualities which were used, the response characteristics of the EPID did not
      depend on energy. Differences in relative dose-response curves resulted from
      energy dependent temporal output characteristics of the accelerator. If ghosting
      is prevented from affecting the results and all dose-response effects are
      properly corrected for, the EPID signal becomes independent of dose rate, dose,
      and exposure time.

PMID- 16279060
TI  - Monte Carlo modeling of the response of NRC's 90Sr/90Y primary beta standard.
AB  - The BEAMnrc/EGSnrc Monte Carlo code system is employed to develop a model of the
      National Research Council of Canada primary standard of absorbed dose to tissue
      in a beta radiation field, comprising an extrapolation chamber and 90Sr/90Y beta
      source. We benchmark the model against the measured response of the chamber in
      terms of absorbed dose to air, for three different experimental setups when
      irradiated by the 90Sr/90Y source. For the first setup, the chamber cavity depth
      is fixed at 0.2 cm and the source-to-chamber distance varied between 11 and 60
      cm. In the other two cases, the source-to-chamber distance is fixed at 30 cm. In
      one case the response for different chamber depths is studied, while in the other
      case the chamber depth is fixed at 0.2 cm as different thicknesses of Mylar are
      added to the front surface of the extrapolation chamber. The agreement as a
      function of distance between the calculated and measured responses is within
      0.37% for a variation in response of a factor of 29. In the case of dose versus
      chamber depth, the agreement is within 0.4% for the ISO-recommended nominal
      depths of 0.025-0.25 cm. Agreement between calculated and measured responses is
      very good (between 0.02% and 0.2%) for added Mylar foils of thicknesses up to
      10.8 mg cm(-2). For larger Mylar thicknesses, deviations of 0.6%-1.2% are
      observed, which are possibly due to the systematic uncertainties associated with
      the restricted collisional stopping powers of air or Mylar used in the
      calculations. We conclude that our simulation model represents the extrapolation
      chamber and 90Sr/90Y source with adequate accuracy to calculate correction
      factors for accurate realization of dose rate to tissue at a depth of 7 mg cm(-2)
      in an ICRU tissue phantom, despite the fact that the uncertainties in the
      physical characteristics of the source leave some uncertainty in certain
      calculated quantities.

PMID- 16279063
TI  - Optimal steel thickness combined with computed radiography for portal imaging of
      nasopharyngeal cancer patients.
AB  - The poor image quality of conventional metal screen-film portal imaging system
      has long been of concern, and various methods have been investigated in an
      attempt to enhance the quality of portal images. Computed radiography (CR) used
      in combination with a steel plate displays image enhancement. The optimal
      thickness of the steel plate had been studied by measuring the modulation
      transfer function (MTF) characteristics. Portal images of nasopharyngeal
      carcinoma patients were taken by both a conventional metal screen-film system and
      this optimal steel and CR plate combination system. Compared with a conventional
      metal screen-film system, the CR-metal screen system achieves a much higher image
      contrast. The measured modulation transfer function (MTF) of the CR combination
      is greater than conventional film-screen portal imaging systems and also results
      in superior image performance, as demonstrated by receiver operator
      characteristic (ROC) analysis. This optimal combination steel CR plate portal
      imaging system is capable of producing high contrast portal images conveniently.

PMID- 16279062
TI  - Patient positioning method based on binary image correlation between two edge
      images for proton-beam radiation therapy.
AB  - A new technique based on normalized binary image correlation between two edge
      images has been proposed for positioning proton-beam radiotherapy patients. A
      Canny edge detector was used to extract two edge images from a reference x-ray
      image and a test x-ray image of a patient before positioning. While translating
      and rotating the edged test image, the absolute value of the normalized binary
      image correlation between the two edge images is iteratively maximized. Each time
      before rotation, dilation is applied to the edged test image to avoid a steep
      reduction of the image correlation. To evaluate robustness of the proposed
      method, a simulation has been carried out using 240 simulated edged head front
      view images extracted from a reference image by varying parameters of the Canny
      algorithm with a given range of rotation angles and translation amounts in x and
      y directions. It was shown that resulting registration errors have an accuracy of
      one pixel in x and y directions and zero degrees in rotation, even when the
      number of edge pixels significantly differs between the edged reference image and
      the edged simulation image. Subsequently, positioning experiments using several
      sets of head, lung, and hip data have been performed. We have observed that the
      differences of translation and rotation between manual positioning and the
      proposed method were within one pixel in translation and one degree in rotation.
      From the results of the validation study, it can be concluded that a significant
      reduction in workload for the physicians and technicians can be achieved with
      this method.

PMID- 16279064
TI  - Helical cone beam CT with an asymmetrical detector.
AB  - If a multislice or other area detector is shifted to one side to cover a larger
      field of view, then the data are truncated on one side. We propose a method to
      restore the missing data in helical cone-beam acquisitions that uses measured
      data on the longer side of the asymmetric detector array. The method is based on
      the idea of complementary rays, which is well known in fan beam geometry; in this
      paper we extend this concept to the cone-beam case. Different cases of
      complementary data coverage and dependence on the helical pitch are considered.
      The proposed method is used in our prototype 16-row CT scanner with an asymmetric
      detector and a 700 mm field of view. For evaluation we used scanned body phantom
      data and computer-simulated data. To simulate asymmetric truncation, the full,
      symmetric datasets were truncated by dropping either 22.5% or 45% from one side
      of the detector. Reconstructed images from the prototype scanner with the
      asymmetrical detector show excellent image quality in the extended field of view.
      The proposed method allows flexible helical pitch selection and can be used with
      overscan, short-scan, and super-short-scan reconstructions.

PMID- 16279065
TI  - Stability of a mobile electron linear accelerator system for intraoperative
      radiation therapy.
AB  - The flexibility of mobile electron accelerators, which are designed to be
      transported to an operating room and plugged into a normal 3-phase outlet, make
      them ideal for use in intraoperative radiation therapy. However, their
      transportability may cause trepidation among potential users, who may question
      the stability of such an accelerator over a period of use. In order to address
      this issue, we have studied the short-term stability of the Mobetron system over
      20 daily quality assurance trials. Variations in output generally varied within
      +/-2% for the four energies produced by the unit (4, 6, 9, and 12 MeV) and
      changes in energy produced an equivalent shift of less than 1 mm on the depth
      dose curve. Hours of inactivity, with the Mobetron powered on for use either
      throughout the day or overnight, led to variations in output of about 1%.
      Finally, we have tested the long-term stability of the absolute dose output of
      the Mobetron, which showed a change of about 1% per year.

PMID- 16279066
TI  - A constrained tracking algorithm to optimize plug patterns in multiple isocenter
      gamma knife radiosurgery planning.
AB  - We developed a source blocking optimization algorithm for Gamma Knife
      radiosurgery, which is based on tracking individual source contributions to
      arbitrarily shaped target and critical structure volumes. A scalar objective
      function and a direct search algorithm were used to produce near real-time
      calculation results. The algorithm allows the user to set and vary the total
      number of plugs for each shot to limit the total beam-on time. We implemented and
      tested the algorithm for several multiple-isocenter Gamma Knife cases. It was
      found that the use of limited number of plugs significantly lowered the integral
      dose to the critical structures such as an optical chiasm in pituitary adenoma
      cases. The main effect of the source blocking is the faster dose falloff in the
      junction area between the target and the critical structure. In summary, we
      demonstrated a useful source-plugging algorithm for improving complex multi
      isocenter Gamma Knife treatment planning cases.

PMID- 16279067
TI  - Computed tomography simulation with superquadrics.
AB  - Accurate and efficient simulation of an x-ray transform for representative
      structures plays an important role in research and development of x-ray CT, for
      the evaluation and improvement of CT image reconstruction algorithms, in
      particular. Superquadrics are a family of three-dimensional objects, which can be
      used to model a variety of anatomical structures. In this paper, we propose an
      algorithm for the computation of x-ray transforms for superellipsoids and tori
      with a monochromatic x-ray. Their usefulness is demonstrated by projection and
      reconstruction of a superquadric-based thorax phantom. Our work indicates that
      superquadric modeling provides a more realistic visualization than quadratic
      modeling, and a faster computation than spline methods.

PMID- 16279068
TI  - Comparison of full-field digital mammography to screen-film mammography with
      respect to contrast and spatial resolution in tissue equivalent breast phantoms.
AB  - To determine if the improved contrast resolution of full-field digital
      mammography (FFDM) with reduced spatial resolution allows for superior or equal
      phantom object detection compared with screen-film mammography (SFM). Tissue
      equivalent breast phantoms simulating an adipose to glandular ratio of
      50/50,30/70, and 20/80 were imaged according to each manufacturers'
      recommendation with four full-field digital mammography units (Fuji, Sectra,
      Fischer, and General Electric) and a screen-film mammography unit (MammoMatII
      2000, Siemens, Munich, Germany). A total of 20 images were obtained in both hard-
      and soft-copy formats. For the purpose of soft-copy display, the screen-film hard
      copy images were digitized with a 50 microm micron scanner. Six radiologists,
      experts in breast imaging, and three physicists, experts in scoring mammography
      phantoms, participated in a reader study where each reader scored each phantom
      for visibility of line-pairs and for 24 objects (fibers, clusters of specks, and
      masses). The data were recorded, entered into a database, and analyzed by a mixed
      effect model. The limiting spatial resolution in line-pairs per millimeter
      visible with the digital units was less, regardless of display modality used,
      than that provided by the screen-film unit. The difference was statistically
      significant for the General Electric (p < 0.01) and Fuji digital mammography
      units (p = 0.03). With respect to the number of visible objects, a statistically
      significant higher number could be detected with the screen-film unit as compared
      to the Fischer (p < 0.01) and Sectra (p < 0.01) digital mammography units, but
      there was no significant difference between the other digital units and screen
      film. Overall, there was significantly better performance on the 50/50 phantom
      than with the 30/70 and 20/80 phantoms (p = 0.01, p < 0.01) for object
      visibility. For the digital mammography units, soft-copy display performed better
      than hard-copy display for the Fischer and Sectra images, but worse for Fuji and
      General Electric. In addition, soft-copy display of digitized screen-film images
      was significantly better than hard-copy display (p =0.02) of the original screen
      films for object visibility, but worse for spatial resolution. The higher
      contrast resolution of the FFDM units tested did not result in improved detection
      of line-pair resolution or objects in the phantoms tested versus screen-film
      mammography. The phantom performance of a digital mammography unit seems to be
      influenced by the type of detection task (line-pair resolution versus object
      visibility), the display modality (soft-copy versus hard-copy) chosen to score
      the phantoms, and the parenchymal pattern composition of the phantom.

PMID- 16279069
TI  - Chord-based versus voxel-based methods of electron transport in the skeletal
      tissues.
AB  - Anatomic models needed for internal dose assessment have traditionally been
      developed using mathematical surface equations to define organ boundaries,
      shapes, and their positions within the body. Many researchers, however, are now
      advocating the use of tomographic models created from segmented patient computed
      tomography (CT) or magnetic resonance (MR) scans. In the skeleton, however, the
      tissue structures of the bone trabeculae, marrow cavities, and endosteal layer
      are exceedingly small and of complex shape, and thus do not lend themselves
      easily to either stylistic representations or in-vivo CT imaging. Historically,
      the problem of modeling the skeletal tissues has been addressed through the
      development of chord-based methods of radiation particle transport, as given by
      studies at the University of Leeds (Leeds, U.K.) using a 44-year male subject. We
      have proposed an alternative approach to skeletal dosimetry in which excised
      sections of marrow-intact cadaver spongiosa are imaged directly via microCT
      scanning. The cadaver selected for initial investigation of this technique was a
      66-year male subject of nominal body mass index (22.7 kg m(-2)). The objectives
      of the present study were to compare chord-based versus voxel-based methods of
      skeletal dosimetry using data from the UF 66-year male subject. Good agreement
      between chord-based and voxel-based transport was noted for marrow irradiation by
      either bone surface or bone volume sources up to 500-1000 keV (depending upon the
      skeletal site). In contrast, chord-based models of electron transport yielded
      consistently lower values of the self-absorbed fraction to marrow tissues than
      seen under voxel-based transport at energies above 100 keV, a feature directly
      attributed to the inability of chord-based models to account for nonlinear
      electron trajectories. Significant differences were also noted in the dosimetry
      of the endosteal layer (for all source tissues), with chord-based transport
      predicting a higher fraction of energy deposition than given by voxel-based
      transport (average factor of about 1.6). The study supports future use of voxel
      based skeletal models which (1) permit nonlinear electron trajectories across the
      skeletal tissues, (2) do not rely on mathematical algorithms for treating the
      endosteal tissue layer, and (3) do not implicitly assume independence of marrow
      and bone trajectories as is the case for chord-based skeletal models.

PMID- 16279070
TI  - The x-ray time of flight method for investigation of ghosting in amorphous
      selenium-based flat panel medical x-ray imagers.
AB  - Amorphous selenium (a-Se) based real-time flat-panel imagers (FPIs) are finding
      their way into the digital radiology department because they offer the practical
      advantages of digital x-ray imaging combined with an image quality that equals or
      outperforms that of conventional systems. The temporal imaging characteristics of
      FPIs can be affected by ghosting (i.e., radiation-induced changes of sensitivity)
      when the dose to the detector is high (e.g., portal imaging and mammography) or
      the images are acquired at a high frame rate (e.g., fluoroscopy). In this paper,
      the x-ray time-of-flight (TOF) method is introduced as a tool for the
      investigation of ghosting in a-Se photoconductor layers. The method consists of
      irradiating layers of a-Se with short x-ray pulses. From the current generated in
      the a-Se layer, ghosting is quantified and the ghosting parameters (charge
      carrier generation rate and carrier lifetimes and mobilities) are assessed. The x
      ray TOF method is novel in that (1) x-ray sensitivity (S) and ghosting parameters
      can be measured simultaneously, (2) the transport of both holes and electrons can
      be isolated, and (3) the method is applicable to the practical a-Se layer
      structure with blocking contacts used in FPIs. The x-ray TOF method was applied
      to an analysis of ghosting in a-Se photoconductor layers under portal imaging
      conditions, i.e., 1 mm thick a-Se layers, biased at 5 V/ microm, were irradiated
      using a 6 MV LINAC x-ray beam to a total dose (ghosting dose) of 30 Gy. The
      initial sensitivity (S0) of the a-Se layers was 63 +/- 2 nC cm(-2) cGy(-1). It
      was found that S decreases to 30% of S0 after a ghosting dose of 5 Gy and to 21%
      after 30 Gy at which point no further change in S occurs. At an x-ray intensity
      of 22 Gy/s (instantaneous dose rate during a LINAC x-ray pulse), the charge
      carrier generation rate was 1.25 +/- 0.1 x 10(22) ehp m(-3) s(-1) and, to a first
      approximation, independent of the ghosting dose. However, both hole and electron
      transport showed a strong dependence on the ghosting dose: hole transport
      decreased by 61%, electron transport by up to approximately 80%. Therefore,
      degradation of both hole and electron transport due to the recombination of
      mobile charge carriers with trapped carriers (of opposite polarity) were
      identified as the main cause of ghosting in this study.

PMID- 16279071
TI  - Photon and electron collimator effects on electron output and abutting segments
      in energy modulated electron therapy.
AB  - In energy modulated electron therapy a large fraction of the segments will be
      arranged as abutting segments where inhomogeneities in segment matching regions
      must be kept as small as possible. Furthermore, the output variation between
      different segments should be minimized and must in all cases be well predicted.
      For electron therapy with add-on collimators, both the electron MLC (eMLC) and
      the photon MLC (xMLC) contribute to these effects when an xMLC tracking technique
      is utilized to reduce the x-ray induced leakage. Two add-on electron collimator
      geometries have been analyzed using Monte Carlo simulations: One isocentric eMLC
      geometry with an isocentric clearance of 35 cm and air or helium in the treatment
      head, and one conventional proximity geometry with a clearance of 5 cm and air in
      the treatment head. The electron fluence output for 22.5 MeV electrons is not
      significantly affected by the xMLC if the shielding margins are larger than 2-3
      cm. For small field sizes and 9.6 MeV electrons, the isocentric design with
      helium in the treatment head or shielding margins larger than 3 cm is needed to
      avoid a reduced electron output. Dose inhomogeneity in the matching region of
      electron segments is, in general, small when collimator positions are adjusted to
      account for divergence in the field. The effect of xMLC tracking on the electron
      output can be made negligible while still obtaining a substantially reduced x-ray
      leakage contribution. Collimator scattering effects do not interfere
      significantly when abutting beam techniques are properly applied.

PMID- 16279073
TI  - Composition of MRI phantom equivalent to human tissues.
AB  - We previously developed two new MRI phantoms (called the CAG phantom and the CAGN
      phantom), with T1 and T2 relaxation times equivalent to those of any human tissue
      at 1.5 T. The conductivity of the CAGN phantom is equivalent to that of most
      types of human tissue in the frequency range of 1 to 130 MHz. In this paper, the
      relaxation times of human tissues are summarized, and the composition of the
      corresponding phantoms are provided in table form. The ingredients of these
      phantoms are carrageenan as the gelling agent, GdCl3 as a T1 modifier, agarose as
      a T2 modifier, NaCl (CAGN phantom only) as a conductivity modifier, NaN3 as an
      antiseptic, and distilled water. The phantoms have T1 values of 202-1904 ms and
      T2 values of 38-423 ms when the concentrations of GdCl3 and agarose are varied
      from 0-140 micromol/kg, and 0%-1.6%, respectively, and the CAGN phantom has a
      conductivity of 0.27-1.26 S/m when the NaCl concentration is varied from 0%-0.7%.
      These phantoms have sufficient strength to replicate a torso without the use of
      reinforcing agents, and can be cut by a knife into any shape. We anticipate the
      CAGN phantom to be highly useful and practical for MRI and hyperthermia-related
      research.

PMID- 16279072
TI  - FTRAC--a robust fluoroscope tracking fiducial.
AB  - C-arm fluoroscopy is ubiquitous in contemporary surgery, but it lacks the ability
      to accurately reconstruct three-dimensional (3D) information. A major obstacle in
      fluoroscopic reconstruction is discerning the pose of the x-ray image, in 3D
      space. Optical/magnetic trackers tend to be prohibitively expensive, intrusive
      and cumbersome in many applications. We present single-image-based fluoroscope
      tracking (FTRAC) with the use of an external radiographic fiducial consisting of
      a mathematically optimized set of ellipses, lines, and points. This is an
      improvement over contemporary fiducials, which use only points. The fiducial
      encodes six degrees of freedom in a single image by creating a unique view from
      any direction. A nonlinear optimizer can rapidly compute the pose of the fiducial
      using this image. The current embodiment has salient attributes: small dimensions
      (3 x 3 x 5 cm); need not be close to the anatomy of interest; and accurately
      segmentable. We tested the fiducial and the pose recovery method on synthetic
      data and also experimentally on a precisely machined mechanical phantom. Pose
      recovery in phantom experiments had an accuracy of 0.56 mm in translation and
      0.33 degrees in orientation. Object reconstruction had a mean error of 0.53 mm
      with 0.16 mm STD. The method offers accuracies similar to commercial tracking
      systems, and appears to be sufficiently robust for intraoperative quantitative C
      arm fluoroscopy. Simulation experiments indicate that the size can be further
      reduced to 1 x 1 X 2 cm, with only a marginal drop in accuracy.

PMID- 16279074
TI  - MOSFET dosimeter depth-dose measurements in heterogeneous tissue-equivalent
      phantoms at diagnostic x-ray energies.
AB  - The objective of the present study was to explore the use of the TN-1002RD metal
      oxide-semiconductor field effect transistor (MOSFET) dosimeter for measuring
      tissue depth dose at diagnostic photon energies in both homogeneous and
      heterogeneous tissue-equivalent materials. Three cylindrical phantoms were
      constructed and utilized as a prelude to more complex measurements within
      tomographic physical phantoms of pediatric patients. Each cylindrical phantom was
      constructed as a stack of seven 5-cm-diameter and 1-cm-thick discs of materials
      radiographically representative of either soft tissue (S), bone (B), or lung
      tissue (L) at diagnostic photon energies. In addition to a homogeneous phantom of
      soft tissue (SSSSSSS), two heterogeneous phantoms were constructed: SSBBSSS and
      SBLLBSS. MOSFET dosimeters were then positioned at the interface of each disc,
      and the phantoms were then irradiated at 66 kVp and 200 mAs. Measured values of
      absorbed dose at depth were then compared to predicated values of point tissue
      dose as determined via Monte Carlo radiation transport modeling. At depths
      exceeding 2 cm, experimental results matched the computed values of dose with
      high accuracy regardless of the dosimeter orientation (epoxy bubble facing toward
      or away from the x-ray beam). Discrepancies were noted, however, between measured
      and calculated point doses near the surface of the phantom (surface to 2 cm
      depth) when the dosimeters were oriented with the epoxy bubble facing the x-ray
      beam. These discrepancies were largely eliminated when the dosimeters were placed
      with the flat side facing the x-ray beam. It is therefore recommended that the
      MOSFET dosimeters be oriented with their flat sides facing the beam when they are
      used at shallow depths or on the surface of either phantoms or patients.

PMID- 16279075
TI  - Feasibility study of helical tomotherapy for total body or total marrow
      irradiation.
AB  - Total body radiation (TBI) has been used for many years as a preconditioning
      agent before bone marrow transplantation. Many side effects still plague its use.
      We investigated the planning and delivery of total body irradiation (TBI) and
      selective total marrow irradiation (TMI) and a reduced radiation dose to
      sensitive structures using image-guided helical tomotherapy. To assess the
      feasibility of using helical tomotherapy, (A) we studied variations in pitch,
      field width, and modulation factor on total body and total marrow helical
      tomotherapy treatments. We varied these parameters to provide a uniform dose
      along with a treatment times similar to conventional TBI (15-30 min). (B) We also
      investigated limited (head, chest, and pelvis) megavoltage CT (MVCT) scanning for
      the dimensional pretreatment setup verification rather than total body MVCT
      scanning to shorten the overall treatment time per treatment fraction. (C) We
      placed thermoluminescent detectors (TLDs) inside a Rando phantom to measure the
      dose at seven anatomical sites, including the lungs. A simulated TBI treatment
      showed homogeneous dose coverage (+/-10%) to the whole body. Doses to the
      sensitive organs were reduced by 35%-70% of the target dose. TLD measurements on
      Rando showed an accurate dose delivery (+/-7%) to the target and critical organs.
      In the TMI study, the dose was delivered conformally to the bone marrow only. The
      TBI and TMI treatment delivery time was reduced (by 50%) by increasing the field
      width from 2.5 to 5.0 cm in the inferior-superior direction. A limited MVCT
      reduced the target localization time 60% compared to whole body MVCT. MVCT image
      guided helical tomotherapy offers a novel method to deliver a precise,
      homogeneous radiation dose to the whole body target while reducing the dose
      significantly to all critical organs. A judicious selection of pitch, modulation
      factor, and field size is required to produce a homogeneous dose distribution
      along with an acceptable treatment time. In addition, conformal radiation to the
      bone marrow appears feasible in an external radiation treatment using image
      guided helical tomotherapy.

PMID- 16279076
TI  - Is it time to retire the CTDI for CT quality assurance and dose optimization?

PMID- 16279077
TI  - Intraoperative image processing for surgical guidance.

PMID- 16279078
TI  - Alignment of sparse freehand 3-D ultrasound with preoperative images of the liver
      using models of respiratory motion and deformation.
AB  - We present a method for alignment of an interventional plan to optically tracked
      two-dimensional intraoperative ultrasound (US) images of the liver. Our clinical
      motivation is to enable the accurate transfer of information from three
      dimensional preoperative imaging modalities [magnetic resonance (MR) or computed
      tomography (CT)] to intraoperative US to aid needle placement for thermal
      ablation of liver metastases. An initial rigid registration to intraoperative
      coordinates is obtained using a set of US images acquired at maximum exhalation.
      A preprocessing step is applied to both the preoperative images and the US images
      to produce evidence of corresponding structures. This yields two sets of images
      representing classification of regions as vessels. The registration then proceeds
      using these images. The preoperative images and plan are then warped to
      correspond to a single US slice acquired at an unknown point in the breathing
      cycle where the liver is likely to have moved and deformed relative to the
      preoperative image. Alignment is constrained using a patient-specific model of
      breathing motion and deformation. Target registration error is estimated by
      carrying out simulation experiments using resliced MR volumes to simulate real US
      and comparing the registration results to a "bronze-standard" registration
      performed on the full MR volume. Finally, the system is tested using real US and
      verified using visual inspection.

PMID- 16279079
TI  - Robust nonrigid registration to capture brain shift from intraoperative MRI.
AB  - We present a new algorithm to register 3-D preoperative magnetic resonance (MR)
      images to intraoperative MR images of the brain which have undergone brain shift.
      This algorithm relies on a robust estimation of the deformation from a sparse
      noisy set of measured displacements. We propose a new framework to compute the
      displacement field in an iterative process, allowing the solution to gradually
      move from an approximation formulation (minimizing the sum of a regularization
      term and a data error term) to an interpolation formulation (least square
      minimization of the data error term). An outlier rejection step is introduced in
      this gradual registration process using a weighted least trimmed squares
      approach, aiming at improving the robustness of the algorithm. We use a patient
      specific model discretized with the finite element method in order to ensure a
      realistic mechanical behavior of the brain tissue. To meet the clinical time
      constraint, we parallelized the slowest step of the algorithm so that we can
      perform a full 3-D image registration in 35 s (including the image update time)
      on a heterogeneous cluster of 15 personal computers. The algorithm has been
      tested on six cases of brain tumor resection, presenting a brain shift of up to
      14 mm. The results show a good ability to recover large displacements, and a
      limited decrease of accuracy near the tumor resection cavity.

PMID- 16279080
TI  - A system for real-time XMR guided cardiovascular intervention.
AB  - The hybrid magnetic resonance (MR)/X-ray suite (XMR) is a recently introduced
      imaging solution that provides new possibilities for guidance of cardiovascular
      catheterization procedures. We have previously described and validated a
      technique based on optical tracking to register MR and X-ray images obtained from
      the sliding table XMR configuration. The aim of our recent work was to extend our
      technique by providing an improved calibration stage, real-time guidance during
      cardiovascular catheterization procedures, and further off-line analysis for
      mapping cardiac electrical data to patient anatomy. Specially designed optical
      trackers and a dedicated calibration object have resulted in a single calibration
      step that can be efficiently checked and updated before each procedure. An X-ray
      distortion model has been implemented that allows for distortion correction for
      arbitrary c-arm orientations. During procedures, the guidance system provides a
      real-time combined MR/X-ray image display consisting of live X-ray images with
      registered recently acquired MR derived anatomy. It is also possible to
      reconstruct the location of catheters seen during X-ray imaging in the MR derived
      patient anatomy. We have applied our registration technique to 13 cardiovascular
      catheterization procedures. Our system has been used for the real-time guidance
      of ten radiofrequency ablations and one aortic stent implantation. We demonstrate
      the real-time guidance using two exemplar cases. In a further two cases we show
      how off-line analysis of registered image data, acquired during electrophysiology
      study procedures, has been used to map cardiac electrical measurements to patient
      anatomy for two different types of mapping catheters. The cardiologists that have
      used the guidance system suggest that real-time XMR guidance could have
      substantial value in difficult interventional and electrophysiological
      procedures, potentially reducing procedure time and delivered radiation dose.
      Also, the ability to map measured electrical data to patient specific anatomy
      provides improved visualization and a path to investigation of cardiac
      electromechanical models.

PMID- 16279081
TI  - Fast generation of digitally reconstructed radiographs using attenuation fields
      with application to 2D-3D image registration.
AB  - Generation of digitally reconstructed radiographs (DRRs) is computationally
      expensive and is typically the rate-limiting step in the execution time of
      intensity-based two-dimensional to three-dimensional (2D-3D) registration
      algorithms. We address this computational issue by extending the technique of
      light field rendering from the computer graphics community. The extension of
      light fields, which we call attenuation fields (AFs), allows most of the DRR
      computation to be performed in a preprocessing step; after this precomputation
      step, DRRs can be generated substantially faster than with conventional ray
      casting. We derive expressions for the physical sizes of the two planes of an AF
      necessary to generate DRRs for a given X-ray camera geometry and all possible
      object motion within a specified range. Because an AF is a ray-based data
      structure, it is substantially more memory efficient than a huge table of
      precomputed DRRs because it eliminates the redundancy of replicated rays.
      Nonetheless, an AF can require substantial memory, which we address by
      compressing it using vector quantization. We compare DRRs generated using AFs (AF
      DRRs) to those generated using ray casting (RC-DRRs) for a typical C-arm geometry
      and computed tomography images of several anatomic regions. They are
      quantitatively very similar: the median peak signal-to-noise ratio of AF-DRRs
      versus RC-DRRs is greater than 43 dB in all cases. We perform intensity-based 2D
      3D registration using AF-DRRs and RC-DRRs and evaluate registration accuracy
      using gold-standard clinical spine image data from four patients. The
      registration accuracy and robustness of the two methods is virtually identical
      whereas the execution speed using AF-DRRs is an order of magnitude faster.

PMID- 16279082
TI  - Markerless real-time 3-D target region tracking by motion backprojection from
      projection images.
AB  - Accurate and fast localization of a predefined target region inside the patient
      is an important component of many image-guided therapy procedures. This problem
      is commonly solved by registration of intraoperative 2-D projection images to 3-D
      preoperative images. If the patient is not fixed during the intervention, the 2-D
      image acquisition is repeated several times during the procedure, and the
      registration problem can be cast instead as a 3-D tracking problem. To solve the
      3-D problem, we propose in this paper to apply 2-D region tracking to first
      recover the components of the transformation that are in-plane to the
      projections. The 2-D motion estimates of all projections are backprojected into 3
      D space, where they are then combined into a consistent estimate of the 3-D
      motion. We compare this method to intensity-based 2-D to 3-D registration and a
      combination of 2-D motion backprojection followed by a 2-D to 3-D registration
      stage. Using clinical data with a fiducial marker-based gold-standard
      transformation, we show that our method is capable of accurately tracking
      vertebral targets in 3-D from 2-D motion measured in X-ray projection images.
      Using a standard tracking algorithm (hyperplane tracking), tracking is achieved
      at video frame rates but fails relatively often (32% of all frames tracked with
      target registration error (TRE) better than 1.2 mm, 82% of all frames tracked
      with TRE better than 2.4 mm). With intensity-based 2-D to 2-D image registration
      using normalized mutual information (NMI) and pattern intensity (PI), accuracy
      and robustness are substantially improved. NMI tracked 82% of all frames in our
      data with TRE better than 1.2 mm and 96% of all frames with TRE better than 2.4
      mm. This comes at the cost of a reduced frame rate, 1.7 s average processing time
      per frame and projection device. Results using PI were slightly more accurate,
      but required on average 5.4 s time per frame. These results are still
      substantially faster than 2-D to 3-D registration. We conclude that motion
      backprojection from 2-D motion tracking is an accurate and efficient method for
      tracking 3-D target motion, but tracking 2-D motion accurately and robustly
      remains a challenge.

PMID- 16279083
TI  - Computer-aided placement of deep brain stimulators: from planning to
      intraoperative guidance.
AB  - In current practice, optimal placement of deep-brain stimulators (DBSs) used to
      treat movement disorders in patients with Parkinson's disease and essential
      tremor is an iterative procedure. A target is chosen preoperatively based on
      anatomical landmarks identified on magnetic resonance images. This point is used
      as an initial position that is refined intraoperatively using both microelectrode
      recordings and macrostimulation. In this paper, we report on our current progress
      toward developing a system for the computer-assisted preoperative selection of
      target points and for the intraoperative adjustment of these points. The system
      consists of a deformable atlas of optimal target points that can be used to
      select automatically the preoperative target, of an electrophysiological atlas,
      and of an intraoperative interface. Results we have obtained show that automatic
      prediction of target points is an achievable goal. Our results also indicate that
      electrophysiological information could be used to resolve structures not visible
      in anatomic images, thus improving both preoperative and intraoperative guidance.
      Our intraoperative system has reached the stage of a working prototype and we
      compare targeting accuracy as well as the number of paths needed to reach the
      targets with our system and with the method in current clinical use.

PMID- 16279084
TI  - Compensating for intraoperative soft-tissue deformations using incomplete surface
      data and finite elements.
AB  - Image-guided liver surgery requires the ability to identify and compensate for
      soft tissue deformation in the organ. The predeformed state is represented as a
      complete three-dimensional surface of the organ, while the intraoperative data is
      a range scan point cloud acquired from the exposed liver surface. The first step
      is to rigidly align the coordinate systems of the intraoperative and preoperative
      data. Most traditional rigid registration methods minimize an error metric over
      the entire data set. In this paper, a new deformation-identifying rigid
      registration (DIRR) is reported that identifies and aligns minimally deformed
      regions of the data using a modified closest point distance cost function. Once a
      rigid alignment has been established, deformation is accounted for using a
      linearly elastic finite element model (FEM) and implemented using an incremental
      framework to resolve geometric nonlinearities. Boundary conditions for the
      incremental formulation are generated from intraoperatively acquired range scan
      surfaces of the exposed liver surface. A series of phantom experiments is
      presented to assess the fidelity of the DIRR and the combined DIRR/FEM approaches
      separately. The DIRR approach identified deforming regions in 90% of cases under
      conditions of realistic surgical exposure. With respect to the DIRR/FEM
      algorithm, subsurface target errors were correctly located to within 4 mm in
      phantom experiments.

PMID- 16279085
TI  - A fully automated calibration method for an optical see-through head-mounted
      operating microscope with variable zoom and focus.
AB  - Ever since the development of the first applications in image-guided therapy
      (IGT), the use of head-mounted displays (HMDs) was considered an important
      extension of existing IGT technologies. Several approaches to utilizing HMDs and
      modified medical devices for augmented reality (AR) visualization were
      implemented. These approaches include video-see through systems, semitransparent
      mirrors, modified endoscopes, and modified operating microscopes. Common to all
      these devices is the fact that a precise calibration between the display and
      three-dimensional coordinates in the patient's frame of reference is compulsory.
      In optical see-through devices based on complex optical systems such as operating
      microscopes or operating binoculars-as in the case of the system presented in
      this paper-this procedure can become increasingly difficult since precise camera
      calibration for every focus and zoom position is required. We present a method
      for fully automatic calibration of the operating binocular Varioscope M5 AR for
      the full range of zoom and focus settings available. Our method uses a special
      calibration pattern, a linear guide driven by a stepping motor, and special
      calibration software. The overlay error in the calibration plane was found to be
      0.14-0.91 mm, which is less than 1% of the field of view. Using the motorized
      calibration rig as presented in the paper, we were also able to assess the
      dynamic latency when viewing augmentation graphics on a mobile target; spatial
      displacement due to latency was found to be in the range of 1.1-2.8 mm maximum,
      the disparity between the true object and its computed overlay represented
      latency of 0.1 s. We conclude that the automatic calibration method presented in
      this paper is sufficient in terms of accuracy and time requirements for standard
      uses of optical see-through systems in a clinical environment.

PMID- 16279086
TI  - Augmented virtuality based on stereoscopic reconstruction in multimodal image
      guided neurosurgery: methods and performance evaluation.
AB  - Displaying anatomical and physiological information derived from preoperative
      medical images in the operating room is critical in image-guided neurosurgery.
      This paper presents a new approach referred to as augmented virtuality (AV) for
      displaying intraoperative views of the operative field over three-dimensional (3
      D) multimodal preoperative images onto an external screen during surgery. A
      calibrated stereovision system was set up between the surgical microscope and the
      binocular tubes. Three-dimensional surface meshes of the operative field were
      then generated using stereopsis. These reconstructed 3-D surface meshes were
      directly displayed without any additional geometrical transform over preoperative
      images of the patient in the physical space. Performance evaluation was achieved
      using a physical skull phantom. Accuracy of the reconstruction method itself was
      shown to be within 1 mm (median: 0.76 mm +/- 0.27), whereas accuracy of the
      overall approach was shown to be within 3 mm (median: 2.29 mm +/- 0.59),
      including the image-to-physical space registration error. We report the results
      of six surgical cases where AV was used in conjunction with augmented reality. AV
      not only enabled vision beyond the cortical surface but also gave an overview of
      the surgical area. This approach facilitated understanding of the spatial
      relationship between the operative field and the preoperative multimodal 3-D
      images of the patient.

PMID- 16279088
TI  - [Vistas in research of regional incidence of malignant tumors. 1955].

PMID- 16279087
TI  - An augmented reality system for patient-specific guidance of cardiac catheter
      ablation procedures.
AB  - We present a system to assist in the treatment of cardiac arrhythmias by catheter
      ablation. A patient-specific three-dimensional (3-D) anatomical model,
      constructed from magnetic resonance images, is merged with fluoroscopic images in
      an augmented reality environment that enables the transfer of electrocardiography
      (ECG) measurements and cardiac activation times onto the model. Accurate mapping
      is realized through the combination of: a new calibration technique, adapted to
      catheter guided treatments; a visual matching registration technique, allowing
      the electrophysiologist to align the model with contrast-enhanced images; and the
      use of virtual catheters, which enable the annotation of multiple ECG
      measurements on the model. These annotations can be visualized by color coding on
      the patient model. We provide an accuracy analysis of each of these components
      independently. Based on simulation and experiments, we determined a segmentation
      error of 0.6 mm, a calibration error in the order of 1 mm and a target
      registration error of 1.04 +/- 0.45 mm. The system provides a 3-D visualization
      of the cardiac activation pattern which may facilitate and improve diagnosis and
      treatment of the arrhytmia. Because of its low cost and similar advantages we
      believe our approach can compete with existing commercial solutions, which rely
      on dedicated hardware and costly catheters. We provide qualitative results of the
      first clinical use of the system in 11 ablation procedures.

PMID- 16279089
TI  - [Use of plastic surgery in management of malignancies. 1956].

PMID- 16279090
TI  - [The development and state of the art of Russian onco-orthopedics].

PMID- 16279091
TI  - [Prognostic factors in soft-tissue sarcoma].

PMID- 16279092
TI  - [Current aspects of surgical treatment for primary and metastatic tumors of the
      spine combined with radiation and chemotherapy].

PMID- 16279093
TI  - [Comparison of methods of reconstructive vascular and microvascular surgery used
      in management of tumors].
AB  - Choice of procedure of treatment of defects of reconstructive surgery for locally
      advanced tumors is discussed. Part 1 deals with use of autovenous vessels and
      synthetic prosthetics for management of chief artery defects, while Part 2--with
      bone, soft tissue and skin defects as well as combination defects. Experience
      with application of free grafts and flaps in microvascular anastomosis is
      evaluated and relevant recommendations are given.

PMID- 16279094
TI  - [Thymidylate synthase, thymidine phosphorylase and dihydropyrimidine
      dehydrogenase expression in soft-tissue sarcoma versus capecitabine potential].
AB  - Expression of thymidylate synthase (TS), thymidine phosphorylase (TP) and
      dihydropyrimidine dehydrogenase (DPD) can predict for clinical outcome of
      fluoropyrimidine-based therapy and there is every likelihood that relevant tumors
      will respond. High TP expression was observed in 35 (42%) patients with soft
      tissue sarcoma. Seven out of 26 (27%) such patients revealed molecular phenotype
      prognostically favorable for capecitabine therapy. More clinical research is
      required to assess the efficacy of capecitabine-based therapy.

PMID- 16279095
TI  - [Vascular endothelial growth factor and two types of its receptors in breast
      cancer].
AB  - Levels of VEGF, VEGFR-1 and VEGFR-2 were determined by enzyme immunoassay in
      tumor and adjacent normal tissue samples from 39 breast cancer patients. Those
      parameters were significantly higher in tumor tissue. Direct correlations were
      established between VEGF and VEGFR-1, on the one hand, and VEGF and VEGFR-2, on
      the other. VEGF expression in breast tumor was relatively higher at earlier
      stages of tumor growth. VEGF and VEGFR-1 expression was consistently higher in
      progesterone receptor negative tumors.

PMID- 16279096
TI  - [The role of clinical and imaging criteria in risk assessment during preoperative
      chemotherapy for osteosarcoma].
AB  - Prognosis for stage IIB osteosarcoma was evaluated versus the role of
      preoperative management of clinico-radiologic status in 293 patients. Three--five
      preoperative intra-arterial cycles of doxorubicin 90mg/m2 or cisplatin 120mg/m2
      were given in 1986-1999, and later were followed by 3-4 cycles of doxorubicin and
      cisplatin in similar doses. Clinico-radiologic status was assessed in the course
      of preoperative chemotherapy. One hundred fifty patients were alive at the last
      examination, 139 had died of tumor progression, and 4 - chemotherapy
      complication. The two courses of preoperative chemotherapy were followed by more
      favorable outcome. Complete clinical response, tumors downsized to 300 mm, intra
      osseous healing, periosteal assimilation and margination of extra-osseous masses
      had a significant positive impact on disease-free survival in the chemotherapy
      group. The data were used for the developing of models for individual risk
      evaluation and prognosis. Clinico-radiologic status monitoring in the course of
      preoperative chemotherapy is instrumental in predicting risks as well as
      designing alternative strategies of treatment at earlier stages.

PMID- 16279098
TI  - [Monophasic synovial sarcoma: comparison of immunohistochemical and
      ultrastructural phenotypes and problems of differential diagnosis].
AB  - Diagnostics of monophasic synovial sarcoma is highly complicated mostly due to a
      wide range of cellular and histologic variation. This calls for use of additional
      examination techniques such as immunohistochemical and electron microscopic.

PMID- 16279097
TI  - [The features of expression of cellular adhesion molecules in primary colorectal
      cancer and its metastases].
AB  - Features of expression, distribution and interaction of E-cadherin, beta-catenin
      and CD-44v6 were immunologically assayed in samples from primary colorectal
      tumors (129) and their metastases to the lymph nodes (35) and liver (92).
      Reduction or total absence of E-cadherin expression was significantly more
      typical of tumors metastasizing, at different stages, to the liver (64/84, 76%)
      than in metastasis-free ones (14/45, 31%) (p=0.014). Enhanced cytoplasmic
      immunoreactivity and beta-catenin nuclear translocation occurred in 80% of
      disseminated tumors. Such alterations of E-cadherin, beta-catenin expression may
      be regarded as unfavorable prognosis factors involved in colorectal cancer. No
      significant correlation between CD-44v6 expression and tumor cell ability to
      metastasize was recorded.

PMID- 16279099
TI  - [Infectious complications after prosthesis implantation in patients with bone
      tumors].
AB  - Data on the retrospective analysis of 245 cases of endoprosthetic replacement of
      bones and major joints are presented. Intraprosthetic infection-related
      complications were reported in 11%. They developed within 3 months in 64% and
      their frequency was significantly higher in cases of repeat surgery, resection of
      proximal tibia with subsequent endoprosthetic replacement of defective knee joint
      as well as adjuvant polychemotherapy. Anti-infective treatment alone was
      effective in 11%; complications were aborted by means of surgery of varying
      extent in 75%.

PMID- 16279100
TI  - [Thermoradiotherapy as a component of desmoid tumor management: 10-year
      experience].
AB  - Data on radio- and thermoradiotherapy of 83 patients with extra-abdominal desmoid
      tumors are discussed. In a group of 57 patients followed up for 10 years or less,
      the relapse-free survival rates, in thermoradiotherapy-treated cases, were
      significantly higher (74.4% and 28.6%) than in those receiving radiotherapy (9.3%
      and 57.1%). Monitoring tumor temperature during local hyperthermia is a factor of
      relapse-free survival of vital importance.

PMID- 16279101
TI  - [Thermoradiochemotherapy of inoperable soft-tissue sarcoma].
AB  - Three groups of patients with inoperable soft-tissue sarcoma received
      preoperative radiotherapy (57), thermoradiotherapy (102) and
      thermoradiochemotherapy (16) (n=175). Five year recurrence-free survival in group
      1 was 37+/-7%, group 2 48+/-6%, and group 3 - 56+/-1,7%. Patients survived 5
      years and more in group 3 (60+/-2%), group 2 - 50+/-7%, and group I 44+/-8%
      (p>0.05). Local hyperthermia used in conjunction with radio- and
      chemoradiotherapy was followed by a significant rise in the rate of complete and
      partial tumor regression.

PMID- 16279102
TI  - [Radiotherapy as a component of treatment for Ewing's sarcoma].
AB  - The main stages of development of such conservative modalities as radio- and
      chemoradiotherapy for localized Ewing's sarcoma are discussed. Factors affecting
      five-year overall and recurrence-free survival of patients treated with
      chemoradiotherapy are presented.

PMID- 16279103
TI  - [Expression of epidermal growth factor receptor (EGFR) in ovarian carcinoma stage
      III-IV].
AB  - Hyperexpression of epidermal growth factor receptor (EGFR) is often identified as
      unfavorable prognosis for different epithelial cancers. The study was concerned
      with an attempt of establishing a relationship between EGFR expression, on the
      one hand, and patient's clinico-morphological status, prognosis and efficacy of
      chemotherapy for stage III-IV serous ovarian carcinoma, on the other. EGFR
      hyperexpression predominated in advanced aggressive tumors and involved a
      significantly shorter period preceding tumor progression. Similarly, overall
      survival median in patients with EGFR hyperexpression (21+/-4 months) appeared
      lower than without it (42+/-8 months). In serous ovarian carcinoma stage III-IV,
      EGFR hyperexpression should be considered sufficient for prognosis of
      chemotherapy efficacy, pre-progression time and survival.

PMID- 16279105
TI  - [Use of endoscopy for sacral resection: a clinical case].
AB  - A case of clinical application of endoscopy in the course of surgery for sacral
      resection is discussed. Video-assisted frontal approach was used to ligate
      internal ileac vessels and to detach the fore end of tumor. Subsequently, the
      sacrum was removed via back access. Unlike standard methods using trans- or
      extraperitoneal frontal approach, our procedure involved less trauma and was
      followed by a shorter rehabilitation period.

PMID- 16279104
TI  - [Pre- and early natal exposure to geomagnetic field as risk for melanoma and
      basal cell skin tumors].
AB  - Histories of 173 male and female patients with melanoma and basal cell skin
      tumors (BCST) were followed to elucidate the influence of pre- and early natal
      exposure to geomagnetic field (GMF) on future incidence of cancer. A positive
      correlation was established between exposure to GMF during critical months of
      prenatal period, on the one hand, and melanoma detection, on the other. However,
      a similar correlation involving BCST was inverse which suggests a difference in
      the etiologies. Tumor regression coefficients which link total Ki-indices for
      critical months of pre- and early natal exposure with tumor detection time are
      presented.

PMID- 16279106
TI  - [Results of repeat large-scale dissection of soft-tissue sarcoma following non
      radical removal].
AB  - The reports deals with the data on repeat large-scale dissection of soft-tissue
      sarcoma following non-radical removal in 23 patients (13 males and 10 females ,
      aged 14-75; mean age 42+/-30.2 yrs). Repeat surgery was carried out 3-6 weeks
      after primary one. Tumor progression was registered in 8 (34.8%): local
      recurrences which required radical intervention 4 (17.4%), distant metastases - 6
      (26.1%) (lung - 3; liver - 1; lung and mediastinal lymph nodes - 1; lung and
      lumbar vertebra - 1). During the study, 5 patients died of tumor progression; all
      of them revealed distant metastases while 2 had local recurrences. Overall 5-year
      survival in 23 patients was 78%; whereas disease-free one - 65%.

PMID- 16279108
TI  - [The use of minimally invasive procedures for diagnosis and therapy of patients
      with spinal tumors].

PMID- 16279107
TI  - [Surgical treatment for pathologic fractures of long tubular bones in metastatic
      cancer].
AB  - Surgery for pathological fracture of long tubular bones associated with
      metastatic cancer was given to 77 patients (1993-2000): segmental resection with
      endoprosthetic replacement - 26; intramedullary osteosynthesis - 17; perosseous
      extrafocal osteosynthesis - 34. No intraoperative complication was reported.
      Infection-related postoperative complications, mainly in perosseous
      osteosynthesis, developed in 5 (7%). All patients were self-sufficient on days 3
      10 after operation.

PMID- 16279109
TI  - [Range of combined treatment of locally advanced skin cancer].
AB  - Due to combined use of surgery, chemo- and radiotherapy, 58.8% of patients with
      locally advanced squamous cell carcinoma survived for 5 years. More organ-saving
      operations could be performed as a result of administering cisplatin, bleomycin
      and 5-fluorouracil chemotherapy in conjunction with radiation and subsequent
      surgery. Greater extent of tumor excision and microsurgery involved lower
      incidence of relapse. Yet, the preliminary results of our combined treatment
      pointed to relatively high frequency of objective response matched by lower
      incidence of relapse which calls for further investigation.

PMID- 16279110
TI  - [Experience with use of mustoforan at the Clinical Oncological Dispensary of the
      Republic of Tatarstan].

PMID- 16279111
TI  - [Health suppliers or service representatives?].

PMID- 16279112
TI  - [A campaign to struggle against rude behavior].

PMID- 16279113
TI  - [Avian influenza reinforcement of protective measures].

PMID- 16279114
TI  - [Responsibilities the nurse].

PMID- 16279115
TI  - [Stoma therapy, in the past and today].

PMID- 16279116
TI  - [New treatments for urinary incontinence in adults].

PMID- 16279117
TI  - [Measures or palliative treatments for urinary incontinence].

PMID- 16279118
TI  - [Fecal incontinence, fecal soiling is not fatal].

PMID- 16279119
TI  - [Illustration of diabetes and its small inconveniences].

PMID- 16279120
TI  - [Changes in hospitals].

PMID- 16279121
TI  - [Hospitals, transformations without end].

PMID- 16279122
TI  - [Public hospitals, impossible to reform?].

PMID- 16279123
TI  - [The role of nursing care following reform of the health care system in Canada].

PMID- 16279124
TI  - [The organization by sections at the University Hospital Center of Toulouse].

PMID- 16279125
TI  - [Hospital reform, what is the future of role of the nurse?].

PMID- 16279126
TI  - [Bibliographic components].

PMID- 16279127
TI  - [Establishing priorities to ensure care for patients].

PMID- 16279129
TI  - [III--Cares at the level of the family. 5. Helping the family to express fear,
      aggression or an anticipation of fear].

PMID- 16279128
TI  - [Preventing accidental exposure to blood].

PMID- 16279130
TI  - Informed patient consent to participation in cluster randomized trials: an
      empirical exploration of trials in primary care.
AB  - Cluster randomized trials are increasingly common. Obtaining informed patient
      consent to participation in these trials raises practical challenges and ethical
      issues. The aims of this paper were to 1) develop a typology of interventions
      employed in cluster randomized trials in primary care; 2) assess whether the
      likelihood of seeking individual consent to participation varies by intervension
      type; 3) assess whether this likelihood has increased over time; 4) assess
      evidence for under reporting of consent procedures; 5) articulate reasons for not
      obtaining consent; and 6) make recommendations for future trial investigators. We
      collected data on trial interventions and consent procedures from reports of 152
      recently published trials, and 47 unpublished trials. We develop a typology of
      interventions based on reasons for adopting a clustered design. We examine
      proportions seeking individual consent to participation among trials involving
      different types of intervention, in different periods, and among published and
      unpublished trials. Two-thirds of the trials had multifaceted interventions.
      Trials involving different types of intervention had different propensities to
      seek consent, largely because of practical obstacles to obtaining consent.
      Obtaining consent can compromise internal validity. More recent trials are no
      more likely to obtain consent than past trials. There was no evidence of under
      reporting of consent procedures in publications. In conclusion, future trial
      investigators should consider both practical reasons and scientific arguments for
      not obtaining individual patient consent for all interventions in their trials.
      Where feasible, they should allow patients to opt out of the trial. Lay
      individuals should represent trial participants as part of the process of cluster
      consent to participation, and lay individuals could also be involved in
      considering ethical issues during trial planning. A more public debate may
      clarify the general acceptability of not obtaining consent in certain situations.

PMID- 16279131
TI  - Determinants of the intracluster correlation coefficient in cluster randomized
      trials: the case of implementation research.
AB  - The objective of this research was to identify determinants of the magnitude of
      intracluster correlation coefficients (ICCs) in cluster randomized trials from
      the field of implementation research. A survey of experts was conducted to
      generate a priori hypotheses of factors that might affect ICC size. Hypotheses
      were tested on empirical estimates of ICCs calculated from 21 implementation
      research datasets, mainly from the UK. Effects of setting (primary or secondary
      care), type of variable (process or outcome), type of measurement (objective or
      subjective), prevalence of outcome and size of cluster were tested. In total, 220
      ICCs were available (range 0 to 0.415). Significant differences in ICC magnitude
      were found. The ICCs were significantly higher for process than for outcome
      variables, and for secondary care outcomes compared with primary care outcomes.
      The effects of prevalence and size were less clear cut. There was no evidence to
      suggest that type of measurement affected ICC size. In conclusion, accurate
      estimates of ICCs are essential for sample size calculations for cluster
      randomized trials of professional behaviour change interventions. This study
      demonstrates that ICCs are sensitive to a number of trial factors, particularly
      setting and outcome type. These factors must be considered when planning such
      cluster randomized trials.

PMID- 16279132
TI  - Prior distributions for the intracluster correlation coefficient, based on
      multiple previous estimates, and their application in cluster randomized trials.
AB  - Numerous estimates for the intracluster correlation coefficient (ICC) are
      available in research databases and publications. When planning a cluster
      randomized trial, an anticipated value for the ICC is required; currently,
      researchers base their choice informally on the magnitude of previous ICC
      estimates. In this paper, we make use of the wealth of ICC information by
      formally constructing informative prior distributions, while acknowledging the
      varying relevance and precision of the estimates available. Typically, for a
      planned trial in a given clinical setting, multiple relevant ICC estimates are
      available from each of several completed studies. Our preferred model allows for
      the imprecision in each ICC estimate around its underlying true value and,
      separately, allows for the similarity of ICC values from the same study. The
      relevance of each previous estimate to the planned clinical setting is
      considered, and estimates corresponding to less relevant outcomes or population
      types are given less influence. We find that such downweighting can increase the
      precision of the anticipated ICC. In trial design, the prior distribution
      constructed allows uncertainty about the ICC to be acknowledged, and we describe
      how to choose a design that provides adequate power across the range of likely
      ICC values. Prior information on the ICC can also be incorporated in analysis of
      the trial data, when taking a Bayesian approach. The methods proposed enable
      available ICC information to be summarised appropriately by an informative prior
      distribution, which is of direct practical use in cluster randomized trials.

PMID- 16279133
TI  - Differential recruitment in a cluster randomized trial in primary care: the
      experience of the UK back pain, exercise, active management and manipulation (UK
      BEAM) feasibility study.
AB  - BACKGROUND: Cluster randomized trials, which randomize groups of patients rather
      than individuals, are commonly used to evaluate healthcare interventions such as
      training programmes targeted at health professionals. This article reports the
      dangers of randomizing entire primary care practices when participants cannot be
      identified before randomization, as shown by a UK national trial. METHOD: The UK
      BEAM trial, a national cluster randomized 3 x 2 x 2 factorial trial, was designed
      to evaluate three treatments for back pain in primary care: "active management";
      randomized by practice; and spinal manipulation and exercise classes, both
      randomized by individual. RESULTS: Two hundred and thirty-one participants were
      recruited in the feasibility study, 165 (141% of expected recruitment) from
      active (management) practices but only 66 (54% of expected recruitment) from
      traditional (management) practices. The participants in active practices were
      significantly different from those in traditional practices, notably in suffering
      from milder back pain. CONCLUSIONS: The feasibility study highlighted the dangers
      of randomizing clusters when individuals cannot be identified beforehand.
      Different numbers and types of participants were recruited in the two types of
      cluster. This differential recruitment led us to change the main trial design by
      abandoning practice level randomization. Instead all practices were trained in
      active management to maximize recruitment. Ideally cluster randomized trials
      should identify patients beforehand, to minimize the chance of selection bias. If
      this is not possible, patient recruitment should be independent in both
      intervention and control clusters. Pilot studies are especially important for
      cluster randomized trials, to identify unforeseen problems.

PMID- 16279134
TI  - Reducing selection bias in a cluster randomized trial in West African villages.
AB  - Selection bias in cluster randomized trials may threaten the validity of the
      results. This bias may occur either at the level of the cluster or of the
      individual. We describe measures for maintaining comparability of intervention
      groups in a cluster randomized trial of a health education package to reduce
      dietary salt. The setting was 12 villages of the Ashanti region of Ghana. In
      total, 1896 villagers between 40 and 75 years of age were selected to take part
      in the trial using stratified random sampling, based on age and sex. Following
      individuals' consent and baseline measurements in a pair of villages, villages
      were randomized to intervention or control arms, stratified for locality (semi
      urban or rural). Primary outcomes of the trial were reduction in 24-hour urinary
      sodium and blood pressure. Of the villagers, 1013 individuals agreed to take
      part, with a response rate of 53%. The groups were comparable with respect to
      mean (SD) systolic and diastolic blood pressure (125/74 (27/14) mmHg versus
      126/75 (25/14) mmHg) and other outcomes. In conclusion, in this study blind
      recruitment, aided by randomization in small blocks, and stratified random
      sampling of the subjects within the clusters helped to ensure comparability of
      intervention groups, which is vital for the validity of the trial results.

PMID- 16279135
TI  - Randomization inference for balanced cluster-randomized trials.
AB  - This paper discusses the choice of randomization tests for inferences from
      cluster-randomized trials that have been designed to ensure a balanced allocation
      of clusters to treatments. Methods for covariate-adjusted randomization tests are
      reviewed and their application to balanced cluster-randomized trials discussed.
      Two cluster-randomized trials with balanced designs are used to illustrate the
      choices that can be made in selecting a randomization test, and methods for
      obtaining confidence intervals for treatment effects are illustrated. The balance
      imposed by the randomization in these trials makes adjustment for covariates less
      beneficial than for an unbalanced design. However, the adjusted analyses do not
      appear generally to have worse properties than the unadjusted ones, and may
      provide protection against any imbalance that has not been controlled for in the
      design. The only case when adjustment for covariates may result in worse
      precision is when a large number of cluster-level covariates are included in the
      analysis. An expression is provided that allows the size of this effect to be
      calculated for any given set of cluster-level covariates.

PMID- 16279136
TI  - Standardized mean differences in individually-randomized and cluster-randomized
      trials, with applications to meta-analysis.
AB  - The magnitude of the effect of an intervention on a quantitative outcome may be
      expressed as a standardized mean difference by dividing the difference in means
      by the standard deviation of the outcome. This is useful to compare outcomes
      measured using different scales, especially in meta-analysis. However,
      uncertainty about the standard deviation leads to complicated formulae to avoid
      bias and to compute the correct standard error. We review approximate and exact
      formulae and argue for the use of the exact formulae. We then extend the formulae
      to cluster-randomized trials, and show how the calculations may be implemented
      using published results. We also describe methods for estimating the standard
      deviation. Various pitfalls are identified which can lead to major errors
      especially in the cluster-randomized setting.

PMID- 16279137
TI  - Design and analysis of clinical trials with clustering effects due to treatment.
AB  - Where patients receive therapy as a group, there are good theoretical reasons to
      believe that variation in the outcome will be smaller for patients treated in the
      same group than for patients treated in different groups. Similarly, where
      different therapists treat different groups of patients, outcome for patients
      treated by the same therapist may differ less than outcome for patients treated
      by different therapists. Clinical trials evaluating such therapies need to
      consider this potential lack of independence. As with cluster-randomized trials,
      this has implications for the precision of treatment effects estimates and
      statistical power. There are nevertheless differences between clustering due to
      the organization of treatment and that due to randomization. In cluster
      randomized trials the distribution of cluster sizes in each treatment arm should
      be similar as a consequence of randomization unless there is differential loss to
      follow-up. With clustering due to therapy group or therapist, cluster size may
      differ systematically between treatment arms, due to size of therapy groups or
      differing health professional caseload. Intra-cluster correlation may also differ
      between treatment arms. The implications of differential cluster size and
      intracluster correlation for design and analysis will be illustrated by data from
      two trials, the first comparing nurse practitioner care with general practitioner
      care, and the second comparing a group therapy with individual treatment as
      usual. The special case where a group therapy or therapist is compared with an
      unclustered treatment is examined in detail using a simulation study. The
      implications of differential clustering effects for sample size and power are
      addressed. It is argued that the design and analysis of this type of trial should
      take account of possible heterogeneity in cluster size and intracluster
      correlation.

PMID- 16279138
TI  - The use of random effects models to allow for clustering in individually
      randomized trials.
AB  - BACKGROUND: We describe different forms of clustering that may occur in
      individually randomized trials, where the observed outcomes for different
      individuals cannot be regarded as independent. We propose random effects models
      to allow for such clustering, across a range of contexts and trial designs, and
      investigate their effect on estimation and interpretation of the treatment
      effect. METHODS: We apply our proposed models to two individually randomized
      trials with potential for clustering, a trial of teleconsultation in hospital
      referral (the main outcome being offer of a further hospital appointment) and a
      trial of exercise therapy delivered by physiotherapists for low back pain (the
      outcome being a back pain score). Extensions to the methods include the
      possibility of explaining heterogeneity between clusters using cluster level
      characteristics and the potential dilution of cluster effects due to
      noncompliance. RESULTS: In the teleconsultation trial, the odds ratio was
      significant (1.52, 95% CI 1.27 to 1.82) when clustering was ignored, but smaller
      and nonsignificant (1.36, 95% CI 0.85 to 2.13) when clustering by hospital
      consultant was taken into account. The 95% range of estimated treatment effects
      across consultants was from 0.21 to 8.76. This variability was only partially
      explained by the specialty of the consultant. In the back pain trial, although
      there was an overall benefit of exercise (change of - 0.51 points on the back
      pain score) and little evidence of clustering, the estimated treatment effects
      for different physiotherapists ranged from -1.26 to +0.26 points. CONCLUSIONS:
      Clustering is an important issue in many individually randomized trials. Ignoring
      it can lead to underestimates of the uncertainty and too extreme P-values. Even
      when there is little apparent heterogeneity across clusters, it can still have a
      large impact on the estimation and interpretation of the treatment effect.

PMID- 16279139
TI  - Overlap coefficient for assessing the similarity of pharmacokinetic data between
      ethnically different populations.
AB  - We developed a method to assess the similarity of pharmacokinetic data between
      ethnically different populations. An evaluation of confidence intervals for the
      mean difference in pharmacokinetic parameters, such as area under the
      concentration-versus-time curve (AUC), between populations is often used. We
      propose the use of the overlap coefficient (OC), which represents the proportion
      of overlap between two probability distributions, as a measure of the similarity
      between distributions. We considered five OC estimators--two parametric ones and
      three nonparametric ones. Simulation studies were conducted to compare the
      performance of the five OC estimators and their bootstrap confidence intervals.
      Results showed that nonparametric estimators with fixed-bandwidth kernel density
      estimation had a smaller mean squared error in almost all situations, and their
      coverage probabilities were close to the nominal level. The proposed method was
      applied to pharmacokinetic data from a bridging study of a combination therapy
      for metastatic colorectal cancer patients in the USA and Japan. From the analyses
      of this study, it was suggested that the distributions of the logarithmically
      transformed AUC for leucovorin and 5-fluorouracil were similar between the two
      populations.

PMID- 16279140
TI  - Translational clinical trials: an entropy-based approach to sample size.
AB  - Translational clinical trials are small studies of therapies emerging from the
      laboratory. These trials are essential for generating early evidence regarding
      the effects of treatment on specific targets in the disease pathway and for
      guiding the next studies to be done. The statistical properties of such studies
      have been neglected, in part, because they do not fit the well-known clinical
      trials developmental paradigm. This paper discusses the translational trial
      setting, and presents an information (entropy) based approach to understanding
      the properties and use of these trials. The combination of biological knowledge
      with a designed experiment (albeit a small one) is a powerful device for
      resolving much of the considerable uncertainty surrounding an emerging
      therapeutic concept. An approach to motivating the sample size for translational
      trials is presented.

PMID- 16279141
TI  - The Society for Clinical Trials supports United States legislation mandating
      trials registration.

PMID- 16279142
TI  - Ethics and evidence in clinical trials.

PMID- 16279143
TI  - Where's the utility in Bayesian data-monitoring of clinical trials?
AB  - BACKGROUND: Data monitoring is now an established part of good practice in
      clinical trials. Bayesian procedures for data-monitoring of treatment trials have
      been proposed and used, but sometimes without explicit consideration of
      utilities. A natural statistical framework for evidence-based medicine is a
      Bayesian approach to decision-making that incorporates an integrated summary of
      the available evidence and associated uncertainty with assessment of utilities.
      METHODS: We explore this approach to data monitoring, explicitly addressing
      separately the individual, scientific and public health perspectives. The Data
      Monitoring Committee's decision can then be thought of as a weighted combination
      of these perspectives. These ideas are illustrated with a trial of treatments for
      oesophageal cancer. RESULTS: For a Bayesian approach without explicit utilities
      we show that a utility structure is, in fact, implicit, and that it may be viewed
      as a weighted sum of the individual and scientific utilities. CONCLUSIONS: We
      argue that explicit consideration of utilities leads to decision-making that is
      more transparent, and lays foundations for data monitoring of more complex
      trials.

PMID- 16279144
TI  - Meta-analysis of individual patient data from randomized trials: a review of
      methods used in practice.
AB  - BACKGROUND: Meta-analyses based on individual patient data (IPD) are regarded as
      the gold standard for systematic reviews. However, the methods used for analysing
      and presenting results from IPD meta-analyses have received little discussion.
      METHODS: We review 44 IPD meta-analyses published during the years 1999-2001. We
      summarize whether they obtained all the data they sought, what types of
      approaches were used in the analysis, including assumptions of common or random
      effects, and how they examined the effects of covariates. RESULTS: Twenty-four
      out of 44 analyses focused on time-to-event outcomes, and most analyses (28)
      estimated treatment effects within each trial and then combined the results
      assuming a common treatment effect across trials. Three analyses failed to
      stratify by trial, analysing the data is if they came from a single mega-trial.
      Only nine analyses used random effects methods. Covariate-treatment interactions
      were generally investigated by subgrouping patients. Seven of the meta-analyses
      included data from less than 80% of the randomized patients sought, but did not
      address the resulting potential biases. CONCLUSIONS: Although IPD meta-analyses
      have many advantages in assessing the effects of health care, there are several
      aspects that could be further developed to make fuller use of the potential of
      these time-consuming projects. In particular, IPD could be used to more fully
      investigate the influence of covariates on heterogeneity of treatment effects,
      both within and between trials. The impact of heterogeneity, or use of random
      effects, are seldom discussed. There is thus considerable scope for enhancing the
      methods of analysis and presentation of IPD meta-analysis.

PMID- 16279145
TI  - Randomized controlled trials of aprotinin in cardiac surgery: could clinical
      equipoise have stopped the bleeding?
AB  - BACKGROUND: Aprotinin is a serine protease inhibitor used to limit perioperative
      bleeding and reduce the need for donated blood transfusions during cardiac
      surgery. Randomized controlled trials of aprotinin evaluating its effect on the
      outcome of perioperative transfusion have been published since 1987, and
      systematic reviews were conducted in 1992 and 1997. METHODS: A systematic search
      was conducted for all RCTs of aprotinin that used placebo controls or were open
      label with no active control treatment. Data collected included the primary
      outcome, objective of each study, whether a systematic review was cited or
      conducted as part of the background and/or rationale for the study and the number
      of previously published RCTs cited. Cumulative meta-analyses were performed.
      RESULTS: Sixty-four randomized, controlled trials of aprotinin were found,
      conducted between 1987 and 2002, reporting an endpoint of perioperative
      transfusion. Median trial size was 64 subjects, with a range of 20 to 1784. A
      cumulative meta-analysis indicated that aprotinin greatly decreased the need for
      perioperative transfusion, stabilizing at an odds ratio of 0.25 (p < 10 - 6) by
      the 12th study, published in June of 1992. The upper limit of the confidence
      interval never exceeded 0.65 and results were similar in all subgroups. Citation
      of previous RCTs was extremely low, with a median of 20% of prior trials cited.
      Only 7 of 44 (15%) of subsequent reports referenced the largest trial (N = 1784),
      which was 28 times larger than the median trial size. CONCLUSIONS: This study
      demonstrates that investigators evaluating aprotinin were not adequately citing
      previous research, resulting in a large number of RCTs being conducted to address
      efficacy questions that prior trials had already definitively answered.
      Institutional review boards and journals could reduce the number of redundant
      trials by requiring investigators to conduct adequate searches for prior evidence
      and conducting systematic reviews.

PMID- 16279146
TI  - Equipoise in the enhanced supression of the platelet IIb/IIIa receptor with
      integrilin trial (ESPRIT): a critical appraisal.
AB  - Enhanced Supression of the Platelet IIb/IIIa Receptor with Integrilin Trial
      (ESPRIT) was a multicenter randomized controlled clinical trial in which
      participants were randomized between eptifibatide and placebo. A "clinical hold"
      was initially placed on the trial by the US Food and Drug Administration (FDA),
      which was concerned about the placebo-only control arm. The hold was lifted after
      additional information concerning the use of platelet glycoprotein IIb/IIIa
      inhibitors in clinical practice, derived from a survey of interventional
      cardiologists, was provided. The trial's principal investigator and colleagues
      have described how these issues were resolved, and advance a claim of equipoise
      for the trial. In this critical appraisal we examine the information and
      arguments proffered in support of the trial design and conclude that they
      evidence a misunderstanding of equipoise. We believe that a placebo-only control
      arm was not justified by the information provided by the trialists.

PMID- 16279147
TI  - A critical history of individual and collective ethics in the lineage of Lellouch
      and Schwartz.
AB  - The notions of individual and collective ethics were first explicitly defined in
      the biostatistical literature in 1971 to motivate a mathematical solution to a
      posed ethical dilemma. This paper reviews key antecedents to these concepts and
      traces explicit references to them over time, primarily in the biostatistical
      literature. Following a historical exposition of these texts, a critical thematic
      analysis shows the following: the normative force of these concepts has not been
      adequately argued. Individual and collective ethics do not solve the problem of
      how to use accumulating data to inform ethical action. The notions of the
      "individual" and the "collective" are too vague to prompt clear moral
      imperatives, especially in difficult cases. These concepts have not been
      successfully linked to a standard ethical framework. Finally, the paper concludes
      with the observation that a systematic, comprehensive ethical framework must be
      identified to fulfill the intuitions behind individual and collective ethics.

PMID- 16279148
TI  - Unblinding of trial participants to their treatment allocation: lessons from the
      Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).
AB  - BACKGROUND: The gold standard clinical trial design is the double-blind,
      randomized, controlled trial. No standard practice exists for the "unblinding" of
      trial participants and no legal obligation is placed on investigators to inform
      participants of their treatment allocation or study results at the end of a
      trial. Here we document our experiences of unblinding the 2520 Scottish
      participants in the Prospective Study of Pravastatin in the Elderly at Risk
      (PROSPER). METHODS: The objectives of the PROSPER unblinding process were to
      provide all study participants with their study medication status and on-trial
      cholesterol levels and to respect the rights of participants not to be unblinded.
      It was considered imperative by the study executive that the blind was maintained
      until the presentation and publication of the results. Staff therefore remained
      "blinded" throughout the unblinding process. Inappropriate contact with the
      PROSPER participants was avoided by confirming their current vital status and
      health status. RESULTS: To coincide with the presentation of the PROSPER results,
      all participants, for whom it was deemed appropriate, were sent a summary of the
      results and were offered the opportunity to be advised of their treatment
      allocation and on-trial lipid profiles. The majority of participants opted for
      telephone unblinding. All primary care physicians who had patients randomised to
      the study were also sent a summary of the study results and sealed documents
      detailing the treatment allocation and lipid profiles for each patient. Relocated
      patients were traced and the information forwarded to their new primary care
      physicians. CONCLUSION: The dissemination of study results and treatment
      allocation to study participants is an integral part of the research process and
      should be included in the design of any clinical trial.

PMID- 16279149
TI  - The use of systematic reviews when designing studies.
AB  - BACKGROUND: The importance of systematic reviews in identifying gaps in the
      evidence base and providing a quantitative basis for informing new research
      initiatives is widely acknowledged, but little is known about what actually
      happens in practice. Our objective was to assess the use made of results of
      reviews in the designing of new studies. METHODS: Of all Cochrane reviews
      published in 1996, those updated in 2002 or 2003 were identified. Authors of
      trials added in the updates were contacted and asked if use had been made of the
      1996 Cochrane or other reviews in designing their study. RESULTS: Of 32 authors
      of studies newly included in 33 Cochrane reviews which met our inclusion
      criteria, 24 (75%) responded. Eleven (46%) respondents were aware of the relevant
      Cochrane review at the time they designed their study. In eight (33%) cases the
      design of the new study had been influenced by a review; in two (8%) this was the
      relevant Cochrane review. CONCLUSIONS: Cautious interpretation of these results
      is necessary, but it is apparent that the proportion of study investigators using
      Cochrane or other systematic reviews in designing their new studies was very
      limited. Inclusion of encouragement in publication or application guidelines to
      consider and cite review results is desirable.

PMID- 16279151
TI  - Physiotherapy in stable COPD.

PMID- 16279150
TI  - Abstracts presented at the American Society of Clinical Oncology conference: how
      completely are trials reported?
AB  - PURPOSE: To assess how completely trials published in conference proceedings are
      reported and whether this has changed over time. METHODS: Conference abstracts
      published at the American Society of Clinical Oncology (ASCO) conference (1992
      and 2002) were read to identify reports of randomized trials. A checklist was
      devised (based on CONSORT) to assess the completeness of reporting. RESULTS: Four
      hundred and ninety-four abstracts reporting randomized trials were identified;
      209 in 1992 and 285 in 2002. More trials included "randomized" in the title in
      2002 compared to 1992 (54% versus 36%). Almost no trials stated the method of
      allocation concealment, 12% stated the method of blinding, 95% described eligible
      participants and 98% described the interventions. Ninety-five per cent reported
      the number of participants in each trial. The median number of participants per
      trial increased over time; 120 in 1992 and 209 in 2002 (P < 0.01). In 1992, 67%
      of trials reported the number of participants analysed, compared to only 49% in
      2002 (P < 0.01), 28% reported or suggested intention to treat analysis dropping
      to 15% in 2002. Twenty-nine abstracts in 2002 and five in 1992 reported no
      results, with a promise of presentation at the meeting. CONCLUSIONS: The
      reporting of conference abstracts for trials should be improved to further
      facilitate understanding of their conduct and validity.

PMID- 16279152
TI  - Supported and unsupported arm exercise capacity following lung volume reduction
      surgery: a pilot study.
AB  - STUDY OBJECTIVES: Lung volume reduction surgery (LVRS) has been shown to improve
      lung function, leg exercise capacity and quality of life in subjects with severe
      COPD. This is the first study to examine the effect of LVRS on supported and
      unsupported arm exercise capacity. DESIGN: Eight subjects with COPD (% pred FEV1
      +/- SD = 31.1 +/- 9.8%) completed testing. At baseline (T1), after eight weeks
      pulmonary rehabilitation (T2) and four months after LVRS (T3), each subject had
      tests of lung function, and performed three symptom-limited exercise tests to
      peak work capacity: supported arm exercise (SAE), unsupported arm exercise (UAE)
      and leg exercise (LE). MEASUREMENTS: The FEV1 (% pred) increased from 27.8 +/-
      7.4 (mean +/- SD) at T2 to 36.3 +/- 7.1 at T3 (P < 0.05). Peak oxygen consumption
      (VO2) remained similar from T1 to T2 for SAE, UAE and LE (all P = 1.0) but
      increased from T2 to T3 (P < 0.05) (SAE: T2 = 0.59 +/- 0.2 L/min, T3 = 0.72 +/-
      0.1 L/min; UAE: T2 = 0.45 +/- 0.1 L/min, T3 = 0.54 +/- 0.1 L/min; LE: T2 = 0.68
      +/- 0.2 L/min, T3 = 0.81 +/- 0.2 L/min). The ratio of end-expiratory lung volume
      to total lung capacity was reduced at peak SAE and LE from T2 to T3 (P < 0.01)
      (SAE: T2 = 81 +/- 4.0%, T3 = 76 +/- 2.7%; LE: T2 = 81 +/- 5.1%, T3 = 75 +/-
      3.6%). CONCLUSION: There was a significant increase in SAE and UAE capacity
      following LVRS. Dynamic hyperinflation was reduced during SAE following LVRS.

PMID- 16279154
TI  - Chronic Respiratory Diseases. Rare lung diseases. Introduction.

PMID- 16279153
TI  - An evaluation of the acute impact of pursed lips breathing on walking distance in
      nonspontaneous pursed lips breathing chronic obstructive pulmonary disease
      patients.
AB  - This study was designed to test the effects of pursed lips breathing (PLB) during
      exercise in patients with chronic obstructive pulmonary disease (COPD) who did
      not spontaneously perform PLB. Sixty-nine COPD patients, mean FEV1 (SD) 1.09
      (0.5), age 68 (51-83) were recruited to the study. They performed three
      incremental shuttle walk tests (ISWT). The first walk was designed to identify
      natural PLBs and the next two walks were performed in a random order; ISWT + PLB
      or ISWT whilst breathing normally. Measures of respiratory rate (RR),
      breathlessness and oxygen saturation were taken before and after walks. Data was
      analysed using the t-test. Fifteen patients demonstrated PLB on baseline ISWT and
      were therefore excluded from further walking tests although baseline data was
      included in the analysis. There was no significant difference between walks, mean
      (SD), 298.5 (173.7) PLB and non-PLB; 292.5 (161.9) nor any difference in
      dyspnoea. There was a significant reduction in end exercise RR and recovery time
      with PLB, mean difference (95% CI); 6.2 (4.5-7.9) and 24.9 (2.8-47.0) seconds,
      respectively. Patients who showed a good response with the PLB walk (41%) had
      significantly higher baseline breathlessness, Borg score, mean (SD), 1.5 (1.0)
      versus 0.74 (0.96) (P = 0.02). Natural PLB patients demonstrated lower exercise
      tolerance on the baseline walk (P = 0.01) and a trend towards greater resting
      breathlessness than those who did not. This study shows PLB during exercise and
      recovery results in lower post exercise RR and speeds return to pre exercise
      breathlessness, compared with exercise and non-PLB. Reductions in RR appear to be
      greatest in those patients with resting breathlessness.

PMID- 16279155
TI  - Small vessel vasculitis of the lung.
AB  - The diagnosis and management of SVV remains one of the most challenging clinical
      scenarios encountered by a clinician. Careful attention to detail and a thorough
      knowledge of the specific disorders, their therapies, and complications thereof
      is required to optimally care for these patients. The recent completion of a
      number of randomized, controlled, multicenter clinical trials has greatly
      improved our knowledge base and ability to care for vasculitis patient. The next
      decade holds even more promise.

PMID- 16279156
TI  - Macrolides in cystic fibrosis.
AB  - Macrolide antibiotics have been licensed since the 1950s and have an important
      role in the treatment of a diverse range of infectious diseases. Macrolide
      antibiotics have antibacterial activity against gram-positive bacteria, some gram
      negative bacteria and intracellular pathogens. The spectrum of antibacterial
      activity combined with excellent intracellular and tissue penetration has led to
      the extensive use of this class of drugs in respiratory disease. Macrolide
      antibiotics also have demonstrated anti-inflammatory properties in various in
      vitro and in vivo model systems. Novel antimicrobial and anti-inflammatory
      properties of macrolide may result in clinical benefits, particularly in
      conditions where the infectious agent is inherently resistant to macrolides.
      Three randomized control trials have demonstrated improved lung function in
      patients treated with the macrolide antibiotic, azithromycin. Azithromycin was
      generally well tolerated and resulted in reduction in the inflammatory response
      which may be due to an immunomodulatory role. Short term studies (three to six
      months) have not demonstrated the development of increased bacterial resistance
      or the emergence of new pathogens following azithromycin.

PMID- 16279157
TI  - Weaning from long-term mechanical ventilation.
AB  - As many as 5% of patients who need mechanical ventilation will require prolonged
      mechanical ventilation (PMV). The cost of their care and its associated morbidity
      is alarming; however, good outcomes can be achieved when their care is
      specialized and delivered in a programmatic manner. In this article, we review
      some of the common and potentially reversible reasons why patients fail
      successfully liberation from mechanical ventilation. We examine the outcomes of
      patients requiring PMV and present evidence that supports the development of
      specialized units where patients can be cohorted and may produce better outcomes
      than would be likely if these patients remained in the ICU.

PMID- 16279158
TI  - The effect of home oxygen therapy on hospitalization in moderate hypoxaemic COPD.
AB  - BACKGROUND: The aim of the study was to determine whether home oxygen therapy
      (HOT) reduces hospitalization in moderate hypoxaemic COPD patients. METHODS: We
      studied 170 consecutive moderate hypoxaemic COPD patients (PaO2 on room air and
      rest: 7.3-9.5 kPa), who were treated with HOT for at least one month. The
      patients were acting as their own control. Admission rates, days spent in
      hospital and number of patients with at least one hospitalization were compared
      in two periods of 10 months before and after initiation of HOT. RESULTS: The
      admission rates, number of days spent in hospital and number of patients with at
      least one hospitalization was not reduced (preoxygen period versus postoxygen
      period): 1.55 (2.00) versus 1.67 (2.26), 14.3 (19.9) versus 14.8 (23.7), and
      60.6% versus 61.2%--P-level > 0.05 for all three parameters. CONCLUSIONS: Our
      results do not support the hypothesis that home oxygen therapy reduces
      hospitalization in patients with COPD without severe hypoxaemia. However, as this
      is not a randomized study, we cannot exclude that oxygen therapy has prevented
      progression of the disease, and that without this therapy, the hospitalization
      could have been even higher.

PMID- 16279159
TI  - Spirometry should be measured in the offices of general practitioners.

PMID- 16279160
TI  - Limitations to spirometry being performed in 'the office'.

PMID- 16279161
TI  - Short-range intercellular calcium signaling in bone.
AB  - The regulation of bone turnover is a complex and finely tuned process. Many
      factors regulate bone remodeling, including hormones, growth factors, cytokines
      etc. However, little is known about the signals coupling bone formation to bone
      resorption, and how mechanical forces are translated into biological effects in
      bone. Intercellular calcium waves are increases in intracellular calcium
      concentration in single cells, subsequently propagating to adjacent cells, and
      can be a possible mechanism for the coupling of bone formation to bone
      resorption. The aim of the present studies was to investigate whether bone cells
      are capable of communicating via intercellular calcium signals, and determine by
      which mechanisms the cells propagate the signals. First, we found that
      osteoblastic cells can propagate intercellular calcium transients upon mechanical
      stimulation, and that there are two principally different mechanisms for this
      propagation. One mechanism involves the secretion of a nucleotide, possibly ATP,
      acting in an autocrine action to purinergic P2Y2 receptors on the neighboring
      cells, leading to intracellular IP3 generation and subsequent release of calcium
      from intracellular stores. The other mechanism involves the passage of a small
      messenger through gap junctions to the cytoplasm of the neighboring cells,
      inducing depolarization of the plasma membrane with subsequent opening of
      membrane bound voltage-operated calcium channels. Next, we found that osteoblasts
      can propagate these signals to osteoclasts as well. We demonstrated that
      paracrine action of ATP was responsible for the wave propagation, but now the
      purinergic P2X7 receptor was involved. Thus, the studies demonstrate that calcium
      signals can be propagated not only among osteoblasts, but also between
      osteoblasts and osteoclasts in response to mechanical stimulation. Thus,
      intercellular calcium signaling can be a mechanism by which mechanical stimuli on
      bone are translated into biological signals in bone cells, and propagated through
      the network of cells in bone. Further, the observations offer new pharmacological
      targets for the modulation of bone turnover, and perhaps even for the treatment
      of bone metabolic disorders.

PMID- 16279162
TI  - Bethany Care Society responds to Auditor's report.

PMID- 16279163
TI  - Report shows rise in concerns related to legal/ethical scope of practice.

PMID- 16279165
TI  - A multidisciplinary approach to blood pressure management in patients with
      diabetes.

PMID- 16279164
TI  - Fatigue, stress, and fitness to practice.

PMID- 16279166
TI  - New resources on screening for HIV in pregnancy.

PMID- 16279167
TI  - Internet generates new roles for RNs.

PMID- 16279168
TI  - JBEAM: multiscale curve coding via beamlets.
AB  - A multiscale coder for curves and boundaries is presented. It utilizes a
      multiscale structure--beamlets--that is designed primarily for linear and
      curvilinear features. The coder is composed of three main components: 1) a rate
      distortion optimized beamlet-based representation, 2) a tree-based coding from a
      beamlet representation to a symbol stream, and 3) an entropy coder. This coder is
      named "JBEAM." Taking advantage of its multiscale property, we utilized tree
      based coding to make it progressive. The derived coder has a low order of
      computational complexity. Simulations demonstrate an advantage over the state-of
      the-art industrial standard: JBIG 2. A software package, which includes an
      implementation of JBEAM, is made available. Variations and potential improvements
      of this method will be discussed. This work may inspire more activities in this
      line of research, improving curve coding.

PMID- 16279169
TI  - Adaptive snakes using the EM algorithm.
AB  - Deformable models (e.g., snakes) perform poorly in many image analysis problems.
      The contour model is attracted by edge points detected in the image. However,
      many edge points do not belong to the object contour, preventing the active
      contour from converging toward the object boundary. A new algorithm is proposed
      in this paper to overcome this difficulty. The algorithm is based on two key
      ideas. First, edge points are associated in strokes. Second, each stroke is
      classified as valid (inlier) or invalid (outlier) and a confidence degree is
      associated to each stroke. The expectation maximization algorithm is used to
      update the confidence degrees and to estimate the object contour. It is shown
      that this is equivalent to the use of an adaptive potential function which varies
      during the optimization process. Valid strokes receive high confidence degrees
      while confidence degrees of invalid strokes tend to zero during the optimization
      process. Experimental results are presented to illustrate the performance of the
      proposed algorithm in the presence of clutter, showing a remarkable robustness.

PMID- 16279170
TI  - Affine-permutation invariance of 2-D shapes.
AB  - Shapes provide a rich set of clues on the identity and topological properties of
      an object. In many imaging environments, however, the same object appears to have
      different shapes due to distortions such as translation, rotation, reflection,
      scaling, or skewing. Further, the order by which the object's feature points are
      scanned changes, i.e., the order of the pixels may be permuted. Relating two
      dimensional shapes of the same object distorted by different affine and
      permutation transformations is a challenge. We introduce a shape invariant that
      we refer to as the intrinsic shape of an object and describe an algorithm,
      BLAISER, to recover it. The intrinsic shape is invariant to affine-permutation
      distortions. It is a uniquely defined representative of the equivalence class of
      all affine-permutation distortions of the same object. BLAISER computes the
      intrinsic shape from any arbitrarily affine-permutation distorted image of the
      object, without prior knowledge regarding the distortions or the undistorted
      shape of the object. The critical step of BLAISER is the determination of the
      shape orientation and we provide a detailed discussion on this topic. The
      operations of BLAISER are based on low-order moments of the input shape and,
      thus, robust to error and noise. Examples illustrate the performance of the
      algorithm.

PMID- 16279171
TI  - The long-range saliency of edge- and corner-based salient points.
AB  - A major goal of salient-point (SP) detection is increasing computational
      efficiency. Therefore, methods which can detect saliency of a large region by
      evaluation of only a small local patch are of particular interest. This paper
      checks for well-known detectors whether saliency outreaches the actual SPs.

PMID- 16279172
TI  - Adaptive active appearance models.
AB  - The active appearance model (AAM) is a powerful tool for modeling images of
      deformable objects and has been successfully used in a variety of alignment,
      tracking, and recognition applications. AAM uses subspace-based deformable models
      to represent the images of a certain object class. In general, fitting such
      complicated models to previously unseen images using standard optimization
      techniques is a computationally complex task because the gradient matrix has to
      be numerically computed at every iteration. The critical feature of AAM is a fast
      convergence scheme which assumes that the gradient matrix is fixed around the
      optimal coefficients for all images. Our work in this paper starts with the
      observation that such a fixed gradient matrix inevitably specializes to a certain
      region in the texture space, and the fixed gradient matrix is not a good estimate
      of the actual gradient as the target texture moves away from this region. Hence,
      we propose an adaptive AAM algorithm that linearly adapts the gradient matrix
      according to the composition of the target image's texture to obtain a better
      estimate for the actual gradient. We show that the adaptive AAM significantly
      outperforms the basic AAM, especially in images that are particularly challenging
      for the basic algorithm. In terms of speed and accuracy, the idea of a linearly
      adaptive gradient matrix presented in this paper provides an interesting
      compromise between a standard optimization technique that recomputes the gradient
      at every iteration and the fixed gradient matrix approach of the basic AAM.

PMID- 16279173
TI  - The Rician inverse Gaussian distribution: a new model for non-Rayleigh signal
      amplitude statistics.
AB  - In this paper, we introduce a new statistical distribution for modeling non
      Rayleigh amplitude statistics, which we have called the Rician inverse Gaussian
      (RiIG) distribution. It is a mixture of the Rice distribution and the inverse
      Gaussian distribution. The probability density function (pdf) is given in closed
      form as a function of three parameters. This makes the pdf very flexible in the
      sense that it may be fitted to a variety of shapes, ranging from the Rayleigh
      shaped pdf to a noncentral chi2-shaped pdf. The theoretical basis of the new
      model is quite thoroughly discussed, and we also give two iterative algorithms
      for estimating its parameters from data. Finally, we include some modeling
      examples, where we have tested the ability of the distribution to represent
      locale amplitude histograms of linear medical ultrasound data and single-look
      synthetic aperture radar data. We compare the goodness of fit of the RiIG model
      with that of the K model, and, in most cases, the new model turns out as a better
      statistical model for the data. We also include a series of log-likelihood tests
      to evaluate the predictive performance of the proposed model.

PMID- 16279175
TI  - A universal noise removal algorithm with an impulse detector.
AB  - We introduce a local image statistic for identifying noise pixels in images
      corrupted with impulse noise of random values. The statistical values quantify
      how different in intensity the particular pixels are from their most similar
      neighbors. We continue to demonstrate how this statistic may be incorporated into
      a filter designed to remove additive Gaussian noise. The result is a new filter
      capable of reducing both Gaussian and impulse noises from noisy images
      effectively, which performs remarkably well, both in terms of quantitative
      measures of signal restoration and qualitative judgements of image quality. Our
      approach is extended to automatically remove any mix of Gaussian and impulse
      noise.

PMID- 16279174
TI  - Inclusion filters: a class of self-dual connected operators.
AB  - In this paper, we define a connected operator that either fills or retains the
      holes of the connected sets depending on application-specific criteria that are
      increasing in the set theoretic sense. We refer to this class of connected
      operators as inclusion filters, which are shown to be increasing, idempotent, and
      self dual (gray-level inversion invariance). We demonstrate self duality for 8
      adjacency on a discrete Cartesian grid. Inclusion filters are defined first for
      binary-valued images, and then the definition is extended to grayscale imagery.
      It is also shown that inclusion filters are levelings, a larger class of
      connected operators. Several important applications of inclusion filters are
      demonstrated-automatic segmentation of the lung cavities from magnetic resonance
      imagery, user interactive shape delineation in content-based image retrieval,
      registration of intravital microscopic video sequences, and detection and
      tracking of cells from these sequences. The numerical performance measures on 100
      cell tracking experiments show that the use of inclusion filter improves the
      total number of frames successfully tracked by five times and provides a
      threefold reduction in the overall position error.

PMID- 16279176
TI  - Robust estimation approach for blind denoising.
AB  - This work develops a new robust statistical framework for blind image denoising.
      Robust statistics addresses the problem of estimation when the idealized
      assumptions about a system are occasionally violated. The contaminating noise in
      an image is considered as a violation of the assumption of spatial coherence of
      the image intensities and is treated as an outlier random variable. A denoised
      image is estimated by fitting a spatially coherent stationary image model to the
      available noisy data using a robust estimator-based regression method within an
      optimal-size adaptive window. The robust formulation aims at eliminating the
      noise outliers while preserving the edge structures in the restored image.
      Several examples demonstrating the effectiveness of this robust denoising
      technique are reported and a comparison with other standard denoising filters is
      presented.

PMID- 16279178
TI  - Toward a generic evaluation of image segmentation.
AB  - Image segmentation plays a major role in a broad range of applications.
      Evaluating the adequacy of a segmentation algorithm for a given application is a
      requisite both to allow the appropriate selection of segmentation algorithms as
      well as to tune their parameters for optimal performance. However, objective
      segmentation quality evaluation is far from being a solved problem. In this
      paper, a generic framework for segmentation evaluation is introduced after a
      brief review of previous work. A metric based on the distance between
      segmentation partitions is proposed to overcome some of the limitations of
      existing approaches. Symmetric and asymmetric distance metric alternatives are
      presented to meet the specificities of a wide class of applications. Experimental
      results confirm the potential of the proposed measures.

PMID- 16279177
TI  - Blind image restoration with eigen-face subspace.
AB  - Performance of conventional image restoration methods is sensitive to signal-to
      noise ratios. For heavily blurred and noisy human facial images, information
      contained in the eigen-face subspace can be used to compensate for the lost
      details. The blurred image is decomposed into the eigen-face subspace and then
      restored with a regularized total constrained least square method. With
      Generalized cross-validation, a cost function is deduced to include two unknown
      parameters: the regularization factor and one parameter relevant to point spread
      function. It is shown that, in minimizing the cost function, the cost function
      dependence of any one unknown parameter can be separated from the other one,
      which means the cost function can be considered roughly, depending on single
      variable in an iterative algorithm. With realistic constraints on the regularized
      factor, a global minimum for the cost function is achieved to determine the
      unknown parameters. Experiments are presented to demonstrate the effectiveness
      and robustness of the new method.

PMID- 16279179
TI  - Generalized ISAR--part I: an optimal method for imaging large naval vessels.
AB  - We describe a generalized inverse synthetic aperture radar (ISAR) process that
      performs well under a wide variety of conditions common to the naval ISAR tests
      of large vessels. In particular, the generalized ISAR process performs well in
      the presence of moderate intensity ship roll. The process maps localized
      scatterers onto peaks on the ISAR plot. However, in a generalized ISAR plot, each
      of the two coordinates of a peak is a fixed linear combination of the three ship
      coordinates of the scatterer causing the peak. Combining this process with
      interferometry will then provide high-accuracy three-dimensional location of the
      important scatterers on a ship. We show that ISAR can be performed in the
      presence of simultaneous roll and aspect change, provided the two Doppler rates
      are not too close in magnitude. We derive the equations needed for generalized
      ISAR, both roll driven and aspect driven, and test them against simulations
      performed in a variety of conditions, including large roll amplitudes.

PMID- 16279180
TI  - Generalized ISAR--part II: interferometric techniques for three-dimensional
      location of scatterers.
AB  - This paper is the second part of a study dedicated to optimizing diagnostic
      inverse synthetic aperture radar (ISAR) studies of large naval vessels. The
      method developed here provides accurate determination of the position of
      important radio-frequency scatterers by combining accurate knowledge of ship
      position and orientation with specialized signal processing. The method allows
      for the simultaneous presence of substantial Doppler returns from both change of
      roll angle and change of aspect angle by introducing generalized ISAR ates. The
      first paper provides two modes of interpreting ISAR plots, one valid when roll
      Doppler is dominant, the other valid when the aspect angle Doppler is dominant.
      Here, we provide, for each type of ISAR plot technique, a corresponding
      interferometric ISAR (InSAR) technique. The former, aspect-angle dominated InSAR,
      is a generalization of standard InSAR; the latter, roll-angle dominated InSAR,
      seems to be new to this work. Both methods are shown to be efficient at
      identifying localized scatterers under simulation conditions.

PMID- 16279181
TI  - Isotropic polyharmonic B-splines: scaling functions and wavelets.
AB  - In this paper, we use polyharmonic B-splines to build multidimensional wavelet
      bases. These functions are nonseparable, multidimensional basis functions that
      are localized versions of radial basis functions. We show that Rabut's elementary
      polyharmonic B-splines do not converge to a Gaussian as the order parameter
      increases, as opposed to their separable B-spline counterparts. Therefore, we
      introduce a more isotropic localization operator that guarantees this
      convergence, resulting into the isotropic polyharmonic B-splines. Next, we focus
      on the two-dimensional quincunx subsampling scheme. This configuration is of
      particular interest for image processing because it yields a finer scale
      progression than the standard dyadic approach. However, up until now, the design
      of appropriate filters for the quincunx scheme has mainly been done using the
      McClellan transform. In our approach, we start from the scaling functions, which
      are the polyharmonic B-splines and, as such, explicitly known, and we derive a
      family of polyharmonic spline wavelets corresponding to different flavors of the
      semi-orthogonal wavelet transform; e.g., orthonormal, B-spline, and dual. The
      filters are automatically specified by the scaling relations satisfied by these
      functions. We prove that the isotropic polyharmonic B-spline wavelet converges to
      a combination of four Gabor atoms, which are well separated in the frequency
      domain. We also show that these wavelets are nearly isotropic and that they
      behave as an iterated Laplacian operator at low frequencies. We describe an
      efficient fast Fourier transform-based implementation of the discrete wavelet
      transform based on polyharmonic B-splines.

PMID- 16279182
TI  - Building robust wavelet estimators for multicomponent images using Stein's
      principle.
AB  - Multichannel imaging systems provide several observations of the same scene which
      are often corrupted by noise. In this paper, we are interested in multispectral
      image denoising in the wavelet domain. We adopt a multivariate statistical
      approach in order to exploit the correlations existing between the different
      spectral components. Our main contribution is the application of Stein's
      principle to build a new estimator for arbitrary multichannel images embedded in
      additive Gaussian noise. Simulation tests carried out on optical satellite images
      show that the proposed method outperforms conventional wavelet shrinkage
      techniques.

PMID- 16279183
TI  - Optimization of integer wavelet transforms based on difference correlation
      structures.
AB  - In this paper, a novel lifting integer wavelet transform based on difference
      correlation structure (DCCS-LIWT) is proposed. First, we establish a relationship
      between the performance of a linear predictor and the difference correlations of
      an image. The obtained results provide a theoretical foundation for the following
      construction of the optimal lifting filters. Then, the optimal prediction lifting
      coefficients in the sense of least-square prediction error are derived. DCCS-LIWT
      puts heavy emphasis on image inherent dependence. A distinct feature of this
      method is the use of the variance-normalized autocorrelation function of the
      difference image to construct a linear predictor and adapt the predictor to
      varying image sources. The proposed scheme also allows respective calculations of
      the lifting filters for the horizontal and vertical orientations. Experimental
      evaluation shows that the proposed method produces better results than the other
      well-known integer transforms for the lossless image compression.

PMID- 16279184
TI  - Reconstructing arbitrarily focused images from two differently focused images
      using linear filters.
AB  - We present a novel filtering method for reconstructing an all-in-focus image or
      an arbitrarily focused image from two images that are focused differently. The
      method can arbitrarily manipulate the degree of blur of the objects using linear
      filters without segmentation. The filters are uniquely determined from a linear
      imaging model in the Fourier domain. An effective and accurate blur estimation
      method is developed. The simulation results show that the accuracy and
      computational time of the proposed method are improved compared with the previous
      iterative method and that the effects of blur estimation error on the quality of
      the reconstructed image are very small. The method performs well for real images
      acquired without visible artifacts.

PMID- 16279185
TI  - Super-resolution reconstruction of hyperspectral images.
AB  - Hyperspectral images are used for aerial and space imagery applications,
      including target detection, tracking, agricultural, and natural resource
      exploration. Unfortunately, atmospheric scattering, secondary illumination,
      changing viewing angles, and sensor noise degrade the quality of these images.
      Improving their resolution has a high payoff, but applying super-resolution
      techniques separately to every spectral band is problematic for two main reasons.
      First, the number of spectral bands can be in the hundreds, which increases the
      computational load excessively. Second, considering the bands separately does not
      make use of the information that is present across them. Furthermore, separate
      band super-resolution does not make use of the inherent low dimensionality of the
      spectral data, which can effectively be used to improve the robustness against
      noise. In this paper, we introduce a novel super-resolution method for
      hyperspectral images. An integral part of our work is to model the hyperspectral
      image acquisition process. We propose a model that enables us to represent the
      hyperspectral observations from different wavelengths as weighted linear
      combinations of a small number of basis image planes. Then, a method for applying
      super resolution to hyperspectral images using this model is presented. The
      method fuses information from multiple observations and spectral bands to improve
      spatial resolution and reconstruct the spectrum of the observed scene as a
      combination of a small number of spectral basis functions.

PMID- 16279186
TI  - Polyphase antialiasing in resampling of images.
AB  - Changing resolution of images is a common operation. It is also common to use
      simple, i.e., small, interpolation kernels satisfying some "smoothness" qualities
      that are determined in the spatial domain. Typical applications use linear
      interpolation or piecewise cubic interpolation. These are popular since the
      interpolation kernels are small and the results are acceptable. However, since
      the interpolation kernel, i.e., impulse response, has a finite and small length,
      the frequency domain characteristics are not good. Therefore, when we enlarge the
      image by a rational factor of (L/M), two effects usually appear and cause a
      noticeable degradation in the quality of the image. The first is jagged edges and
      the second is low-frequency modulation of high-frequency components, such as
      sampling noise. Both effects result from aliasing. Enlarging an image by a factor
      of (L/M) is represented by first interpolating the image on a grid L times finer
      than the original sampling grid, and then resampling it every M grid points.
      While the usual treatment of the aliasing created by the resampling operation is
      aimed toward improving the interpolation filter in the frequency domain, this
      paper suggests reducing the aliasing effects using a polyphase representation of
      the interpolation process and treating the polyphase filters separately. The
      suggested procedure is simple. A considerable reduction in the aliasing effects
      is obtained for a small interpolation kernel size. We discuss separable
      interpolation and so the analysis is conducted for the one-dimensional case.

PMID- 16279187
TI  - Wireless image transmission using turbo codes and optimal unequal error
      protection.
AB  - A novel image transmission scheme is proposed for the communication of set
      partitioning in hierarchical trees image streams over wireless channels. The
      proposed scheme employs turbo codes and Reed-Solomon codes in order to deal
      effectively with burst errors. An algorithm for the optimal unequal error
      protection of the compressed bitstream is also proposed and applied in
      conjunction with an inherently more efficient technique for product code
      decoding. The resulting scheme is tested for the transmission of images over
      wireless channels. Experimental evaluation clearly demonstrates the superiority
      of the proposed transmission system in comparison to well-known robust coding
      schemes.

PMID- 16279188
TI  - A Bayesian framework for noise covariance estimation using the facet model.
AB  - In image processing literature, thus far, researchers have assumed the
      perturbation in the data to be white (or uncorrelated) having a covariance matrix
      sigma2I, i.e., assumption of equal variance for all the data samples and that no
      correlation exists between the data samples. However, there have been very few
      attempts to estimate noise characteristics under the assumption that there is a
      correlation between data samples. In this work, we propose a new and a novel
      approach for the simultaneous Bayesian estimation of the unknown colored or
      correlated noise (population) covariance matrix and the hyperparameters of the
      covariance model using the well-known facet model. We also estimate the facet
      model coefficients. We use the facet model because of its simple, yet elegant,
      mathematical formulation. We use the generalized inverted Wishart density as the
      prior model for the noise covariance matrix. We place a structure on the
      covariance matrix using the parameters of a correlation filter. These
      hyperparameters are estimated by a new extension of the expectation-maximization
      algorithm called the generalized constrained expectation maximization algorithm
      that we developed.

PMID- 16279189
TI  - No-reference quality assessment using natural scene statistics: JPEG2000.
AB  - Measurement of image or video quality is crucial for many image-processing
      algorithms, such as acquisition, compression, restoration, enhancement, and
      reproduction. Traditionally, image quality assessment (QA) algorithms interpret
      image quality as similarity with a "reference" or "perfect" image. The obvious
      limitation of this approach is that the reference image or video may not be
      available to the QA algorithm. The field of blind, or no-reference, QA, in which
      image quality is predicted without the reference image or video, has been largely
      unexplored, with algorithms focusing mostly on measuring the blocking artifacts.
      Emerging image and video compression technologies can avoid the dreaded blocking
      artifact by using various mechanisms, but they introduce other types of
      distortions, specifically blurring and ringing. In this paper, we propose to use
      natural scene statistics (NSS) to blindly measure the quality of images
      compressed by JPEG2000 (or any other wavelet based) image coder. We claim that
      natural scenes contain nonlinear dependencies that are disturbed by the
      compression process, and that this disturbance can be quantified and related to
      human perceptions of quality. We train and test our algorithm with data from
      human subjects, and show that reasonably comprehensive NSS models can help us in
      making blind, but accurate, predictions of quality. Our algorithm performs close
      to the limit imposed on useful prediction by the variability between human
      subjects.

PMID- 16279190
TI  - Modeling visual attention's modulatory aftereffects on visual sensitivity and
      quality evaluation.
AB  - With the fast development of visual noise-shaping related applications (visual
      compression, error resilience, watermarking, encryption, and display), there is
      an increasingly significant demand on incorporating perceptual characteristics
      into these applications for improved performance. In this paper, a very important
      mechanism of the human brain, visual attention, is introduced for visual
      sensitivity and visual quality evaluation. Based upon the analysis, a new
      numerical measure for visual attention's modulatory aftereffects, perceptual
      quality significance map (PQSM), is proposed. To a certain extent, the PQSM
      reflects the processing ability of the human brain on local visual contents
      statistically. The PQSM is generated with the integration of local perceptual
      stimuli from color contrast, texture contrast, motion, as well as cognitive
      features (skin color and face in this study). Experimental results with
      subjective viewing demonstrate the performance improvement on two PQSM-modulated
      visual sensitivity models and two PQSM-based visual quality metrics.

PMID- 16279191
TI  - Senate budget chairman pushes potentially less painful health care savings plan.
      Medicaid, Medicare proposals face opposition from.

PMID- 16279192
TI  - User-fee boost would up safety, reputations. A new paper suggests that drug
      makers, FDA can't afford not to raise user fees.

PMID- 16279193
TI  - WellPoint purchase of wellchoice shakes up health care marketplace. Health plans
      will face tough competition for national products.

PMID- 16279194
TI  - [Isolation and characterization of a novel radiation-resistant rod-shaped
      bacterium].
AB  - A novel radiation-resistant bacterium was isolated from soil of lake bank in
      Beijing. The bacterium produced orange-pigmented colonies and formed rod-shaped
      cells that stained gram negative alike the Deinobacter grandis previously
      described by Japan's scientist. It was found with electron microscopy that the
      isolate is of 0.6 microm - 1.6 microm size and has a 30-40 nm thickness of cell
      wall, being slightly larger and thicker than the Deinobacter grandis. There was a
      difference in the concentration and molecule weight of catalase between the
      isolate and the Deincoccus radiodurans R1. The deoxyribonucleic acid guanine plus
      cytosine (G + C) base ratio was 70.7 mol%. 16S RNA gene sequencing also showed
      that this rod-shaped bacterium possessed a high homology with the Deinobacter
      grandis, suggesting that it might be classified into the genus Deinobacter and
      constitute a new species in this genus.

PMID- 16279195
TI  - [Cloning and functional analysis of promoter pagC from attenuated Salmonella
      typhimurium].
AB  - This study describes the cloning and function of promoter pagC (P(pagC)) from
      Salmonella typhimurium. The expression plasmid containing the in vivo-inducible
      promoter pagC and HGV-NS3 gene was introduced into the attenuated Salmonella
      typhimurium SL7207 to investigate the function of P(pagC). The expressed HGV-NS3
      protein was detectable by SDS-PAGE and Western blotting in the recombinant
      bacteria in the presence of low concentration of Mg2+ (<50 mmol/L). When the
      concentration of Mg2+ reached to 50 mmol/L, the amount of expressed HGV-NS3 was
      decreased significantly. The recombinant bacteria were multiplied in LB medium
      containing 50 mmol/L of Mg2+ and used as a DNA vaccine to orally inoculate C57
      mice for three times. The results of serum antibodies, T lymphocyte proliferative
      response and cytotoxic T lymphocyte response of immunized mice showed that the
      oral vaccine could iuduce strong humoral and cellular immune responses in mice,
      which indicates that the P(pagC) is a strong in vivo-inducible promoter and can
      be used in attenuated Salmonella typhimurium to construct an effective oral
      vaccine.

PMID- 16279196
TI  - [Gene cloning of rpoD and its impact on biosynthesis of antibiotics in
      Fluorescent pseudomonas M18].
AB  - Fluorescent pseudomonas M18, one of plant growth promoting rhizobacteria which
      can inhibit growth of several phytopathogenes, produces several secondary
      metabolites including antibiotics phenazine-1-carboxylic acid (PCA) and
      pyoluteorin (Plt). The rpoD gene encoding the housekeeping sigma factor sigma70
      was cloned and sequenced from M18. Through sequencing and homogeneous comparison,
      the deduced RpoD amino acid sequence between M18 strain and
      Pseudomonasfluorescens CHAO shows 100% identity. It indicates that rpoD gene is
      very conserved in different members of fluorescent pseudomonads. The rpoD gene
      was placed downstream of the constitutive Ptac promoter in the shuttle vector
      pME6032 between E. coli and Pseudomonas fluorescens and the recombinant plasmid
      was introduced into M18. It was found that the time of both PCA and Plt began to
      accumulate was 4 and 8 hours earlier and the yield of these antibiotics was
      increased one and six times more respectively in M18 in comparison with the
      control.

PMID- 16279197
TI  - [Cloning and expression of the apx III A gene of Actinobacillus pleuropneumonie].
AB  - The apx III A gene of Actinobacillus pleuropneumonie (App) was amplified by PCR.
      The amplified DNA fragment 3 466bp was cloned into pMD18-T. After R.E. analysis
      and sequencing, the apx III A gene in pMD18-T was ligated into pBluescrip II
      SK(+), the recombinant expression plasmid pET-28b/apx III A was constructed and
      analysed with R. E., the protein of apx III A gene expressed in E. coli BL21 was
      detected by Western blotting. Based on expressed apx III A protein as antigen,
      empty expression vector as control, the ELISA to detect antibody against apx III
      A was developed and was primarily used to detect serum samples.

PMID- 16279199
TI  - [Complete sequence analysis on potato virus M infecting Solanum muricatum].
AB  - The complete sequence of Potato virus M from Solanum muricatum was determined.
      The liner, single-strand and positive sense genomic RNA was 8526 nucleotides long
      and six open reading frames were identified. The genome organization was typical
      feature of genus Carlavirus. Sequence analysis showed that PVM isolates shared
      62.5% - 97.2% nucleotide and 60.9% - 97.4% amino acid identities. The coat
      protein gene was most conserved and TGB3 gene was greatly variable. Phylogenetic
      tree analysis suggested that the Idaho potato isolate (PVM-Id) was a distant
      strain, and other 4 isolates were grouped discriminatively based on CP and NABP
      amino acid sequences respectively. This is the first report of PVM from Solanum
      muricatum.

PMID- 16279198
TI  - [Cloning and expression of S9-1 gene of rice black-streaked dwarf virus in
      Escherichia coli].
AB  - The cDNA of RBSDV S9 was amplified by RT-PCR using the total RNA of infected
      maize leaves as the template, and then the PCR product was cloned into
      pBluescriptII SK. After the DNA sequence was determined, the S9-1 gene was
      subcloned into E. coli expression vector pET-21d. SDS-PAGE analysis revealed that
      a 40 kD protein was highly expressed. N-terminal sequence analysis confirmed the
      40 kD protein was S9-1 protein. Antiserum was prepared using the purified
      protein. Western blotting indicated that S9-1 protein could be detected in the
      infected maize leaves.

PMID- 16279200
TI  - [Expression of antigenic region of VP1 gene of swine vesicular disease in
      Escherichia coli].
AB  - The antigenic region of VP1 gene of swine vesicular disease virus was amplified
      by reverse transcription polymerase chain reaction (RT-PCR) and nested polymerase
      chain reaction (nPCR). After the amplified fragment was cloned into the
      expression vector pProEX-HTb. The insert position,the size and the reading frame
      of the insertion were identified by PCR, restriction digestion and sequence
      analysis of the recombinant plasmids. SDS-PAGE and Western blot indicated that
      the transformed BL21(DE3) by the recombinant plasmids and induced by IPTG could
      express the antigen region of VP1 of swine vesicular disease virus, the expressed
      antigen protein could be recognized by the positive serum of SVDV.

PMID- 16279201
TI  - [Food-grade expression of human Cu/Zn-superoxide dismutase gene in Lactococcus
      lactis].
AB  - A food-grade gene expression system in L. lactis using the lacF gene as selection
      marker was constructed and further used for food-grade expression of human Cu/Zn
      superoxide dismutase (Cu/Zn SOD). Firstly, an integrative plasmid pUCEmDE
      containing homologous fragments with 0.5 kb flank sequences of the lacF gene was
      constructed. The lacF gene was in-frame deleted by double cross-over between the
      plasmid pUCEmDE and the chromosomal DNA in L. lactis MG5267 and resulted in a
      food-grade host WZ103 that was confirmed by PCR and Lac phenotype examination.
      After that, a complementary plasmid pMG36eF in which the lacF gene was controlled
      by the strong constitutive promoter P32 was electroporated into WZ103 and
      resulted in the restoration of Lac+ phenotype, indicating that the lacF function
      in WZ103 could be complemented by the lacF gene in pMG36eF. Finally, a food-grade
      plasmid pWZ104 used for the expression of Cu/Zn SOD was constructed, in which the
      lacF gene was used as a selective marker instead of any antibiotic resistance
      genes. Expressed Cu/Zn SOD in WZ103 (pWZ104) was demonstrated and showed
      biological activity through non-denatured PAGE and SOD activity gel-staining.

PMID- 16279202
TI  - [Purification and characterization of a uridine phosphorylase from Enterobacter
      aerogenes EAM-Z1].
AB  - A uridine phosphorylase(UPase) was isolation from Enterobacter aerogenes EAM-Z1
      and purified by means of ammonium sulfate precipitation, DEAE-cellulose, Phenyl
      Sepharose, DEAE-Sepharose, FPLC ion exchange, and Sephacryl S-200 column
      chromatography. The purified UPase showed homogeneity on the native polacrylamide
      gel electrophoresis. The UPase is a trimer of 43 kD subunits. Fifteen residues
      from the amino terminal end of UPase were identified as MRMVDLIATKRDGGE. The
      isoelectric point was pH 4.46. Michaelis constant for uridine was 0.29 mmol/L.
      The UPase has a maximal activity at a pH value of 7.8 and 50 degrees C. The UPase
      could catalyses the phosphorolysis of uridine, thymidine, 5-Fluorouridine, 5
      Fluoro-2'-deoxyuridine, uracil-beta-D-arbinofuranoside, and could also catalyse
      the synthesis of 5-Fluorouridine, a better prodrug form of the anticancer drug 5
      fluorouracil, from 5-fluorouracil and uridine, and 47% uridine was converted to 5
      Fluoro-uridine.

PMID- 16279203
TI  - [Relationship between key enzyme activities of inosine-producing pathway and
      inosine accumulation].
AB  - The specific activities of key enzymes relating to the pathway of inosine
      synthesis of three different bacterial strains including high-yield, low-yield
      and wild strains were determined and compared systematically. A close
      relationship between inosine production and the specific activities of key
      enzymes was found. According to the enzyme characteristics of high-yield strain,
      suggestions on further strain improvement by modification of genetic engineering
      were proposed. Enzymology study is believed to be an effective way to make
      screening of high-yield strains more efficient.

PMID- 16279204
TI  - [Biodiversity of bacterial isolates on three different media from coking
      wastewater treatment system].
AB  - Bacteria from coking wastewater treatment sludge samples were directly plated on
      three different isolation media (YPG, LB and WW) and the biodiversity of isolates
      was examined with DNA fingerprinting. Plate counts with YPG, LB and WW media were
      1.6 x 10(6) CFU/mL, 7.0 x 10(5) CFU/mL and 9.8 x 10(5) CFU/mL respectively. 137
      single colony isolates were obtained from these three media. ARDRA with enzymes
      Hinfl revealed 14 operational taxonomic units (OUT) which were dominated by YPG
      OTU1 group accounting for 34 isolates and WW-OTU6 group for 25 isolates. The
      biodiversity of isolates from these two dominant OUT groups was further
      investigated by a genomic fingerprinting technique, ERIC-PCR. The results
      indicated that there were 20 different ERIC-PCR types present among the YPG-OTU1
      group and only 3 among the WW-OTU6 group. The data showed that the populations of
      bacteria isolated on three different media were significantly different from each
      other and a higher degree of genetic diversity was observed among strains
      isolated from YPG media. So YPG may be recommended to be used for a non-selective
      medium for isolating more diversified bacteria from wastewater bio-treatment
      systems.

PMID- 16279205
TI  - [Study on the ammonia-oxidizing bacteria from activated sludge samples by the
      molecular analysis].
AB  - The molecular analysis methods of PCR amplification, random cloning and
      sequencing were used to investigate the ammonia-oxidizing bacterial community
      composition and the activity of ammonia-monooxygenase (AMO) from the activated
      sludge samples of an industrial wastewater treatment plant receiving sewage with
      high ammonia concentration. It is the first time to use PCR-DGGE combined
      technique to analysis the difference of dominant bacterial community compositions
      of the activated sludge samples in China. The result showed that the ammonia
      oxidizing bacteria (AOB) detected from the activated sludge samples all belong to
      Nitrosomonas sp. The activity of AMO, the stability of bacteria community
      composition and the treatment efficiency of the wastewater treatment system were
      improved evidently, after the activated sludge system was operated for a certain
      extant. It is suggested that the molecular techniques will contribute to our
      understanding of the diversity and function of AOB and will benefit to improve
      the industrial wastewater treatment system.

PMID- 16279206
TI  - [Genetic diversity analysis of Chinese stylo anthracnose pathogens using random
      amplified polymorphic DNA].
AB  - Genetic diversity of 43 Colletotrichum gloeosporioides isolates from stylo in
      China were analyzed using random amplified polymorphic DNA (RAPD) with eight
      arbitrary 10-base oligonucleotide primers compared with 276 isolates from other
      countries including two of Colletotrichum cutaturn based on a wide survey and
      disease sample collection. The results showed a good DNA polymorphism between
      isolates. The amplified fragments were between 0.3-2.8 kb. Chinese isolates were
      grouped in clusters II, III and VI with the majority in cluster VI based on six
      clusters of isolates from South America, the centre of origin of Stylosanthes
      genus. The genetic variation in the Chinese pathogen population was very limited
      compared with that in South America, the centre of host-pathogen diversity. The
      results also showed that a genetic variation in Chinese population of
      Colletotrichum gloeosporioides existed, though this variation was less
      significant. Isolates grouped by geographic origin and host species or genotypes
      indicated isolates from different host species or genotypes had their own
      parasitic specialization on genetic basis and pathogens from different countries
      evolved in their own way relatively.

PMID- 16279207
TI  - [Sequence diversity of the 3' end genome for Zucchini yellow mosaic virus
      isolates].
AB  - The present study analyzed the 3' end sequence of nine mainland isolates of
      Zucchini yellow mosaic virus (ZYMV) genome including the coat protein (CP) gene
      and 3' end un-translated region (UTR). Obtained sequence data was compared with
      previously reported sequences of 16 ZYMV isolates from other regions of the
      world. In a certain degree, similarity of nucleic acid sequence for CP gene was
      found being related with the host origin and geological distribution, but not
      very obvious. Similarity of the CP amino acid sequences deduced from nucleic acid
      sequences of the 25 ZYMV isolates reached a higher sequence similarity and a
      clearer relationship to the host origins than to the geological distributions.
      According to its variation, the amino acid sequence of ZYMV CP was divided into
      two parts--"the high variable region" contains about 41 amino acids at its N end,
      while "the conservative region" includes CP core-region and C termini amino
      acids. Our results showed that the trend of ZYMV variation for its rapid adoption
      for fitness of the ecological condition, especially to host interaction by
      mutation of its genomic RNA.

PMID- 16279208
TI  - [Chemical modification of Streptococcus suis type 2 haemolysin].
AB  - The haemolysin of Streptococcus suis type 2 Jiangsu isolate was purified. Effects
      of protein modification reagents on the haemolysin activity were detected. The
      haemolysin was not affected by PCMB, succinic anhydride (SA), EDC, and N-AI
      modification, and it indicated that sulfhudryl groups, amino groups, carboxyl
      groups and tyrosine residues were not essential to haemolysin activity. The
      haemolysin activity was significantly decreased after NBS, DEPC, 2, 3-Diacetyl,
      H2O2 modification and was greatly increased after DTT modification. The results
      indicated that tryptophane residues, histidine residues, arginine residues and
      disulfides groups seemed to be essential to the haemolysin activity.

PMID- 16279209
TI  - [Study on morphological change of aspergillus flavus damaged by citral with a
      multi-channel micro-spectrophotometer system].
AB  - Citral extracted from litsea cubeb oil was used as antibacterial drug; toxigenic
      and atoxigenic Aspergillus flavus cell (AFC) were used as its target. Multi
      channel micro-spectrophotometer (MMSP) and micro-image analysis were applied.
      Under the pressure of citral, changes in AFC were measured, including items such
      as absorbance, area, perimeter, major axis length and minor axis length. We found
      that toxigenic AFC had two characteristic absorbent peaks at 410 nm and 665 nm,
      and that the waveforms of absorption spectrum of toxigenic and atoxigenic AFC
      migrated and their peak areas increased, and that four morphological parameters
      reduced with citral concentration increasing. The results suggest that citral
      damages selective permeability and structure of membrane to enter to cell, and
      acts on target molecule or organelle to bring changes in physiology and
      biochemistry. In real-time, in-situ and non-invasive situation, the dynamic
      changes in shape and intracellular macromolecule are fastly measured during the
      drugs damage a living cell, which not only provides these changes with necessary
      physical parameters, but also has an importance in theoretical research and
      experimental method.

PMID- 16279210
TI  - [Fusion and apoptosis of epithelial cells induced by muramidase released protein
      of Streptococcus suis type 2].
AB  - The pathogenic role of muramidase released protein (MRP), a virulence factor of
      Streptococcus suis type 2 (SS2) is poorly understood. The purified MRP was co
      incubated with HEp-2 cells to determine the effect of MRP on epithelial cells.
      Under light microscope, two principal morphologic changes were observed. Firstly,
      the cells were fused to form syncytia and a apoptosis followed. Secondly, single
      cell was also induced to apoptosis at high level as 18%, which was verified by
      transmission electron microscopy and flow cytometry. It showed that MRP alone was
      capable of a virulence factor of SS2.

PMID- 16279211
TI  - [Characterization of insecticidal crystal proteins genes from Bacillus
      thuringiensis 4.0718 strain].
AB  - In this study, we rapidly identified Bacillus thuringiensis 4.0718 strain that
      harbored the known cryl and cry2 type genes by a PCR strategy. Three pairs of
      universal oligonucleotide primers were designed to detect all known cry1, cry2
      and cry3 type gene sequences. Then the DNA of the positive strain 4.0718 was
      probed with a set of specific primers. One feature of this screening method was
      that each gene was expected to produce a PCR product having a precise molecular
      weight. PCR products having different sizes probably represented the gene was a
      potentially novel gene. Differentiations among these genes was determined on the
      basis of the electrophoresis patterns of PCR products. Finally, five cry1 type
      genes (cry1 Aa, cry1 Ab, cry1 Ac, cry1 Cb, a novel cry4.5 type genes) and one
      cry2 Ac type gene had been detected from Bacillus thuringiensis 4.0718 strain.

PMID- 16279212
TI  - [Cloning of ipaB gene from Shigella flexneri and its expression in yeast cell].
AB  - ipaB gene amplified from S. flexneri 2a by PCR was cloned into pGBKT7 vector
      (Named pGBKT-ipaB) and sequencing indicated that the amino encoded by the cloned
      gene was the same as the reported; The recombination plasmid pGBKT-ipaB was
      transformed into the yeast strain AH109, in which the fusion expression of IpaB
      was analyzed with SDS-PAGE and Western blotting. This provided the basis for
      screening the interacting protein with IpaB by two hybrid system and
      understanding the function of IpaB in the pathogenesis of S. flexneri further.

PMID- 16279214
TI  - [Research progress of moderately halophilic eubacteria].

PMID- 16279213
TI  - [Isolation of a bacterium producing epoxide hydrolase with high
      enantioselectivity and optimization of fermentation conditions].
AB  - A bacterial strain 463# producing epoxide hydrolase was isolated from oil
      contaminated soils. It showed high enantioselectivity towards styrene oxide, and
      also towards glycidates, such as ethyl phenyl glycidate and ethyl benzyl
      glycidate. The strain was identified as Bacillus sp. The fermentation conditions
      for this strain were optimized. With 1% glucose as carbon source, 1% (NH4)2SO4
      and 0.5% beef extract as nitrogen source, Bacillus sp. 463 grew well and showed
      high epoxide hydrolase activity. In addition, 2-10 mmol/L styrene oxide could
      promote the production of epoxide hydrolase.

PMID- 16279215
TI  - [Microbial functional genomics].

PMID- 16279216
TI  - [Vasospasmolytic effects of acupuncture?].

PMID- 16279217
TI  - [Options for debridement in the therapy of chronic wounds].
AB  - Debridement is defined as the removal of non-vital tissue from wounds. In chronic
      wounds, debridement means the elimination of necrosis as well as the clearing
      away of wound dressings, foreign bodies, and other non-vital substances.
      Sufficient debridement represents one basic prerequisite for a non-delayed wound
      healing process. In addition to treating the causal factors for delayed wound
      healing, debridement should be the first step in an adequate phase-adapted wound
      bed preparation for chronic wounds. This report aims to review the different
      options available in the execution of debridement in chronic wounds. The
      following therapeutic measures are available for the debridement of chronic
      wounds: surgery, maggot therapy, laser, ultrasound, hydrotherapy, wet-to-dry
      method, autolysis, proteolytic enzymes, osmotic or chemical debridement. There is
      no single correct debridement for all patients! Patients are individuals and
      therefore different methods of debridement may make sense. Which therapeutic
      option is chosen is determined by multiple factors. Moreover, depending on the
      wound milieu, the successive application of different methods can be useful.

PMID- 16279218
TI  - [Use of Lactobacillus as a probiotic factor to treat urogenital and intestinal
      infections as well as to prevent and treat allergic diseases].
AB  - Lactobacilli are probiotic micro-organisms that are part of the oral, intestinal
      and urogenital commensal flora. The beneficial effect of these bacterial strains,
      especially the eradication of or protection against pathogenic bacteria and
      yeasts, was shown by several studies. The preventive and therapeutic effect of
      lactobacilli applies to diarrhoea and urogenital infections in particular.
      Lactobacilli also seem to have a protective influence on the development and
      treatment of atopic disease.

PMID- 16279219
TI  - Is there a vasospasmolytic effect of acupuncture in patients with secondary
      Raynaud phenomenon?
AB  - BACKGROUND: Raynaud phenomenon (RP) is a vasospastic disorder of the digital
      arteries. Severe forms are found in patients with connective tissue diseases.
      Vasospasmolytic therapies are often limited by side effects such as orthostatic
      hypotension. PATIENTS/METHODS: We investigated therefore the effect of
      acupuncture in a double blind, placebo-controlled, randomized trial in patients
      with secondary RP. The study was performed during the winter season by licensed
      acupuncturists weekly for 8 weeks (points chosen for the verum group: L.I.4,
      S.J.5, St.36, P.6, Du.20, Ex.28). RESULTS: An improvement was detected in both
      groups but there was no significant effect on clinical symptoms - based on
      patient diaries (average number of attacks before and after treatment: verum 1.9
      +/- 2.0 vs. 1.4 +/- 1.7 attacks/ day and placebo 2.8 +/- 1.8 vs. 1.9 +/- 1.1;
      duration of attacks: verum 15 +/- 12 vs. 12 +/- 9 min. and placebo 31 +/- 17 vs.
      16 +/- 6; n.s.) or on skin microcirculation, measured by local cold testing.
      CONCLUSIONS: A specific vasospasmolytic effect of acupuncture could not be
      proven. This may be due to minor morphologic changes of supplying arteries or a
      severe local defect in endothelial function rather than a neurological
      disturbance which might be influenced by acupuncture. Much larger studies would
      be needed to identify the possible small benefit from acupuncture. If long-term
      relief is not obtained, it is unlikely to be cost-effective.

PMID- 16279220
TI  - [Psoriasis arthritis--long-term treatment of two patients with leflunomide].
AB  - The prodrug leflunomide is an immunomodulatory agent whose M1 metabolite inhibits
      the proliferation of T- and B-lymphocytes. The efficacy of leflunomide in
      rheumatoid arthritis suggests it may be useful psoriasis arthritis. Two patients
      with psoriasis arthritis in whom NSAIDs, glucocorticosteroids, sulfasalazine,
      cyclosporine and methotrexate were not as effective as expected were treated with
      leflunomide for 18 and 27 months. At regular visits examination of the joints
      (according to the ACR criteria) and the skin (PASI), the visual analogue scale
      for pain, and the quality of life (HAQ) were assessed. In both patients
      progression of the joint disease was arrested, pain reduced and quality of life
      improved. The cutaneous findings did not change, even though topical therapy was
      continued. Leflunomide is a long-term treatment option for patients with
      predominantly joint disease. In case of insufficient response, combination with
      other anti-inflammatory drugs, e.g. methotrexate, is possible. As leflunomide has
      little effect on psoriatic skin lesions, additional topical therapy is necessary.

PMID- 16279221
TI  - [Elastolytic granulomas of the legs in familial visceral lymphangiodysplasia with
      chronic lymphedema].
AB  - Annular elastolytic giant cell granuloma is a rare skin condition of unknown
      origin characterized by giant cell granulomas with elastophagocytosis and loss of
      elastic tissue. Sun-exposed areas are most commonly affected. We report on an
      unusual case of elastolytic granulomas developing in chronic lymphedema of the
      legs in a female patient with visceral lymphangiodysplasia.

PMID- 16279222
TI  - [Granulomatous dermatitis following herpes zoster with detection of varicella
      zoster virus DNA].
AB  - The occurrence of a granulomatous inflammation following herpes zoster infection
      is uncommon and its pathogenesis is unclear. A 74-year-old male patient developed
      multiple red-brown papules following a secondary generalized infection with
      varicella zoster virus in the same area. The patient was suffering from a chronic
      lymphocytic B-cell leukaemia. Histopathologically, granulomatous dermatitis with
      multinucleate giant cells was found. Varicella zoster virus DNA was identified by
      polymerase chain reaction in the tissue. After a renewed antiviral therapy, skin
      lesions disappeared completely.

PMID- 16279223
TI  - [Blistering autoimmune dermatoses (II): therapy].

PMID- 16279224
TI  - [Progressive alopecia with pruritus].

PMID- 16279225
TI  - [Grouped blisters and mediastinal tumor in a 50-year-old woman].

PMID- 16279226
TI  - [Assessment of quality of life in dermatology].

PMID- 16279227
TI  - [--what is the lesson?].

PMID- 16279228
TI  - Dermatofibrosarcoma protuberans--an update.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a rare fibroblastic skin tumor of
      intermediate malignancy. Its pathogenesis has not yet been fully clarified.
      Recent basic genetic research has shown chromosomal translocations, generally
      termed "ring chromosomes", in DFSP. These arise from a fusion of chromosome
      regions 17q22 and 22q13, the gene loci which code the alpha chain of type I
      collagen. The diagnosis is made histologically. Differentiation from atypical
      dermatofibroma and dermatomyofibroma, as well as from malignant fibrous
      histiocytoma, whose prognosis is usually much less favorable, can be improved by
      immunostaining for CD 34 and Factor XIIIa. The extent of the tumors can be
      estimated by CT and more precisely with MRI. All these techniques fail to detect
      the fine tumor fascicles extending into the adjacent connective tissue and fat.
      Surgery is the therapy of choice for DFSP. The locally infiltrative growth
      pattern features clinically inapparent extensions which often extend for long
      distances in a horizontal direction. These tumor extensions are best detected by
      uninterrupted histological check of all margins, including the base (3-D
      histology), with paraffin sections. Re-excision of tumor-positive areas until
      tumor-free margins are obtained ("histographic surgery") insures a high cure rate
      (97%) while preserving normal tissue.

PMID- 16279229
TI  - [Cyclooxygenases in the skin].
AB  - Cyclooxygenases (COX)-1 and COX-2 catalyse the key steps of prostaglandin
      biosynthesis and are the major target for non-steroidal anti-inflammatory drugs.
      In general, COX-1 but not COX-2 is expressed in healthy tissues of adults. After
      incision or acute irritant dermatitis, COX-2 is induced transiently. The
      development of UV-induced erythema and edema as well as of skin tumours is
      significantly governed by COX-2 activity. Squamous cell carcinomas and actinic
      keratoses are prominent examples of epithelial tumours with COX-2 overexpression
      in the tumour parenchyma, inflammatory infiltrate and associated vessels.
      According to multi-stage carcinogenesis studies in mouse skin and experiments
      with transgenic mice, there is a causal relationship between aberrant COX-2
      expression and activity in the epithelium and tumour promotion and tumour
      progression. The transgenic overexpression of COX-2 causes an "autopromoted" skin
      phenotype, i.e. it dramatically sensitizes the tissue for the development of
      squamous cell carcinomas. Vice versa, the genetic ablation of COX-2, as well as
      of COX-1, results in a reduced tumour burden in murine skin. A major mechanism by
      which COX-2 contributes to epidermal tumour formation seems to be the disturbance
      of terminal keratinocyte differentiation. Because of these data, selective COX-2
      inhibitors are ranked among the most promising agents for skin cancer prevention
      and therapy.

PMID- 16279231
TI  - [Controversy in dermatology--laser therapy and melanocytic nevi].

PMID- 16279230
TI  - [Dramatic increase in lymphogranuloma venereum among homosexual men in Hamburg].
AB  - Classical sexually transmitted diseases, including syphilis and gonorrhea, have
      recently increased significantly among homosexual men in Hamburg. During the last
      year we also observed an increase in patients with lymphogranuloma venereum (LGV)
      at the ifi-institute in Hamburg. In 2003, we identified 4 homosexual patients
      with LGV in different clinical stages. None of the patients has traveled outside
      Germany. Three of these patients were HIV-infected. In all cases Chlamydia
      trachomatis was identified by SDA (strand displacement amplification) in genital
      swabs or lymph node aspirates. In three cases sequencing of ompA PCR products was
      performed and in each instance revealed the C. trachomatis serovar L2. Other
      important genital pathogens were excluded by specific PCR tests, bacteriological
      and serological tests. LGV should be included in the differential diagnosis of
      anogenital and oral erosions, especially in homosexual patients and HIV-infected
      patients. Novel nucleic acid amplification tests can be used for the rapid and
      reliable diagnosis of LGV by identifying Chlamydia trachomatis.

PMID- 16279232
TI  - [Two cases of frontal fibrosing alopecia in postmenopausal women].
AB  - Frontal fibrosing alopecia (FFA) is an uncommon, slowly progressive, cicatricial
      alopecia which mainly affects postmenopausal women. It is considered to be a
      variant of lichen planopilaris. We describe two postmenopausal women who
      developed over 11 and 24 months an asymptomatic atrophic alopecia, restricted to
      the frontal hairline. The diagnosis of FFA was confirmed by biopsy showing a
      perifollicular lymphocytic infiltrate with fibrosis. Topical corticosteroids, in
      one case combined with minoxidil, administered for 3 months arrested the hair
      loss. The treatment of FFA is often difficult. In most cases, the disease
      resolves spontaneously after several years. Immunomodulators such as
      corticosteroids and calcineurin antagonists should be tried in the early stage of
      FFA (frontal effluvium with perifollicular erythema) in order to arrest the
      disease in its inflammatory phase.

PMID- 16279233
TI  - [Syphilis maligna in an HIV-negative patient].
AB  - A 21-year-old patient with a history of drug addiction presented with
      generalized, centrally-ulcerated papules and haemorrhagic crusts. Initially,
      differential diagnostic considerations included pityriasis lichenoides et
      varioliformis acuta and syphilis. Biopsy and serological testing confirmed the
      latter diagnosis. Syphilis maligna is a rare form of secondary syphilis; symptoms
      include a papulonecrotic exanthem and general malaise with fevers and wasting. In
      the past the disease was described in connection with tuberculosis; today it is
      most often seen in association with HIV.

PMID- 16279234
TI  - [Sarcoidosis, myasthenia gravis and anterior ischaemic optic neuropathy: severe
      side effects of adjuvant interferon-alpha-therapy in malignant melanoma?].
AB  - In dermato-oncology, interferon-alpha is widely used as treatment of cutaneous
      lymphoma and as adjuvant therapy in high risk malignant melanoma. With
      increasingly wide administration of interferon-alpha (IFN-alpha), not only early
      onset side effects, such as influenza-like symptoms, but also uncommon late-onset
      side effects are being recognized. We present three patients with melanoma who
      developed rare side effects in the course of adjuvant IFN-alpha-therapy:
      sarcoidosis, myasthenia gravis and anterior ischaemic optic neuropathy. Based on
      current knowledge a causal relationship between these diseases and the
      administration of IFN-alpha can neither be affirmed or absolutely ruled out.
      Therefore special attention should be paid to such coincidences.

PMID- 16279235
TI  - [Skin and sports].

PMID- 16279236
TI  - [Verruciform hyperkeratoses with erythema of the distal extremities of a 19 year
      old man].

PMID- 16279237
TI  - [Granuloma after ear-piercing].

PMID- 16279238
TI  - [Guidelines for phototoxic and photoallergic reactions].

PMID- 16279239
TI  - [Four years of quality assurance of dermatologic procedures: report from the ABD
      clearing institution].
AB  - BACKGROUND: Expert dermatologic evaluation is the most relevant tool for
      secondary prevention in occupational dermatology in Germany. If there is a
      possibility of a work-related skin disorder in an employee, dermatologists may
      conduct the relevant diagnostic procedures (e.g. patch-and prick-tests, serology)
      at the expenses of the public employers' liability insurance fund (UVT). Most
      dermatologists make careful use of this unparalleled privilege, which is also an
      obligation. However, recently, with an increasing number of dermatologist's
      reports submitted, there have been occasional complaints by the UVT concerning
      overly extensive testing. In 1999 the Task Force on Occupational and
      Environmental Dermatology (ABD) of the German Dermatological Society established
      a clearing procedure. Two experienced occupational dermatologists will-
      separately--give their expert opinion on dermatologist's reports which have been
      forwarded anonymously by the UVT for expert review. RESULTS: Thus far, from May
      1999 to May 2003 155 dermatologist's reports have been submitted to the clearing
      procedure. The complaints were in > 95% of cases considered justified by the
      experts. Their criticism was primarily directed towards excessive testing
      procedures and failure to provide sufficient clinical information. CONCLUSIONS:
      The UVT does not undertake such extensive preventive efforts for any other
      occupational disease. Therefore, quality management of the dermatologist's
      procedure--conducted by dermatologists and providing transparency--is essential
      to maintain and develop this effective tool of secondary prevention for the
      benefit of workers and employers.

PMID- 16279240
TI  - [Piercing--the forgotten allergic problem].

PMID- 16279241
TI  - [After care of melanoma--how much is enough?].

PMID- 16279242
TI  - Recurrent erysipelas: risk factors.
AB  - BACKGROUND: Several systemic and regional risk factors have been described for
      erysipelas. However, those predisposing for recurrent episodes are not well
      defined. MATERIALS AND METHODS: We performed a retrospective analysis of 574
      patients hospitalized in our institution during a 3 year period. The analysis
      included demographic, epidemiologic, and medical chart review data with special
      attention to background disorders. The patients with single and recurrent
      episodes of erysipelas were compared. RESULTS: The recurrent cases occurred
      mainly in the lower limb with several risk factors that were statistically more
      common than in the single episode group including overweight, venous
      insufficiency, lymphedema, tinea pedis, and previous regional surgical
      intervention or trauma. CONCLUSIONS: Patients with erysipelas, especially when it
      involves the lower limb, should be instructed to reduce weight, control venous
      insufficiency and/or lymphedema and to emphasize prevention and treatment of
      tinea pedis. The role of prophylactic antibiotics requires further study.

PMID- 16279243
TI  - [Relevance of histological examination in the diagnosis of autoimmune bullous
      dermatoses].
AB  - The histopathological picture of many autoimmune bullous dermatoses is considered
      to be relatively characteristic. However, different entities may show similar
      histological findings. In addition, the picture depends on both the stage of the
      disease and prior treatment. Autoimmune bullous dermatoses are characterized by
      the production of autoantibodies to structural proteins of the skin. In most
      instances, the autoantigens have been identified and are available as recombinant
      proteins. Utilizing these recombinant forms, specific and sensitive assays have
      been developed for the detection of circulating autoantibodies in the serum. The
      detection of autoantibodies in skin or mucous membranes and/or serum is required
      for the diagnosis of autoimmune bullous dermatoses. The task of the
      dermatopathologist in the diagnostic process of autoimmune bullous dermatoses is
      to describe precisely the histopathological findings, to mention differential
      diagnoses and to recommend how these can be confirmed or excluded by
      immunopathological and immunoserological studies.

PMID- 16279245
TI  - [Trichophyton mentagrophytes var. nodulare--an emerging cause of tinea pedis?].
AB  - BACKGROUND: The spectrum of organisms causing dermatophytoses is changing
      continuously. PATIENTS/METHODS: Two strains of Trichophyton mentagrophytes var.
      nodulare are characterized mycologically; both were isolated for the first time
      in our laboratory within the past 2 years from patients with tinea pedis.
      RESULTS: Distinctive features of Trichophyton mentagrophytes var. nodulare are a
      bright yellow-orange pigmentation of the thallus, a marked exudation of pigment,
      and the development of nodular bodies. Trichophyton mentagrophytes var. nodulare
      is an anthropophilic variety of Trichophyton mentagrophytes causing tinea and
      onychomycosis. CONCLUSIONS: Trichophyton mentagrophytes var. nodulare has been
      found only very rarely in Germany and is relatively unknown. An increased
      awareness of this dermatophyte is needed in order to track its possible spread.

PMID- 16279244
TI  - [Patients' view of melanoma follow-up].
AB  - BACKGROUND: About 20% of melanoma patients develop progressive disease during
      follow-up. This is an alarming number for the patients. In view of new
      recommendations for melanoma follow-up, this study assesses the performance and
      quality of follow-up as perceived by the patients. PATIENTS AND METHODS: A
      questionnaire was distributed to 462 patients with melanoma being followed in the
      skin cancer units of the universities of Cologne and Munster. Follow-up was based
      on recommendations published in 1994 by Malignant Melanoma Committee of the
      German Dermatological Society. RESULTS: Follow-up was regularly performed. In
      Munster, 62% patients were seen in the university clinic, while in Cologne 53% of
      patients were followed jointly by the university clinic and practicing
      dermatologists. Radiological examinations were regularly repeated in 70% of the
      collective. 70% of patients reported performing self-examinations. 14% had
      developed progressive disease. 15% made use of psycho-social help. CONCLUSIONS:
      The questionnaire reveals that the interdisciplinary follow-up and self
      examinations proposed in the new recommendations are already well accepted. Based
      on latest standards, 90% of the patients felt that follow-up was reassuring.
      Psychosocial services should be offered more directly with emphasis on both
      social services and psychological support. Systematic patient inquiries can be
      used to establish quality standards for follow-up which are more patient
      oriented.

PMID- 16279246
TI  - [Squamous cell carcinoma in lupus vulgaris].
AB  - Lupus vulgaris and carcinoma in lupo have become rare events that take place in
      the developed countries only under special circumstances. A 53-year-old woman
      developed such a carcinoma. She suffered from alcoholism, a well known risk
      factor for tuberculosis. The diagnosis of lupus vulgaris was confirmed by biopsy
      when an erythematous lesion on her arm that had been present for 25 years
      enlarged and subsequently ulcerated. Chemotherapy was discontinued because of
      lack of compliance and the ulcer grew markedly over the following 16 months.
      Therefore the entire lesion was excised. Histology showed a squamous cell
      carcinoma within the ulcer. Neither further systemic manifestations of
      tuberculosis nor metastases of the carcinoma were found. Under continuous
      combined antituberculous therapy, the patient remained free of symptoms. This
      case underlines the problems associated with a disease that has been nearly
      forgotten in the western countries. It also shows that alcoholism is a risk
      factor for tuberculosis, along with debilitating diseases such as lymphoma and
      AIDS as well as immunosuppressive therapy.

PMID- 16279248
TI  - [Bullous autoimmune dermatoses (I): Pathogenesis and diagnosis].

PMID- 16279247
TI  - [Argyria--an almost-forgotten dyschromia].
AB  - A 79-year-old woman presented with a long history of grey-blue discoloration of
      the light-exposed areas. Her face, forearms, and the backs of both hands were
      affected. The proximal parts of her fingernails were impressively discolored, but
      her toenails were not affected. The patient reported that she had received oral
      therapy with the silver-containing drug Gastrarctin in 1959. The diagnosis of
      argyria was confirmed by documenting high tissue levels of silver in light
      exposed skin. Argyria has become uncommon as medications containing silver are no
      longer employed and occupational protection for those with exposure to silver
      salts has become more refined.

PMID- 16279249
TI  - [Disseminated erythematous maculae with central bullae formation. Generalized
      fixed drug exanthema].

PMID- 16279250
TI  - [Guideline for vulvovaginal candidiasis. 6 November 2002 status. Professional
      Society of Infections and Infection Immunology of the German Society of
      gynecology and obstetrics and German Language Mycologic Society e.V].

PMID- 16279251
TI  - [Comment on the letter and response regarding "Treatment of psoriasis capilliti
      with Dethranol].

PMID- 16279252
TI  - [Atopic dermatitis guideline--no evidence based recommendations for
      phototherapy].

PMID- 16279253
TI  - Study conduct, monitoring and data management in a trinational trial: the OPTIMA
      model.
AB  - The OPTions In Management with Antiretrovirals (OPTIMA) Trial, a collaboration
      between three governmental agencies in the USA, UK and Canada is a large-scale,
      multicenter, randomized controlled trial designed to compare the relative
      efficacy of different therapeutic strategies in HIV disease. The collaboration of
      three coordinating centers introduced unique data management issues including: a)
      use of different data systems for managing "country" trial data; b) two-way data
      transfer between the coordinating centers and the center where OPTIMA data is
      merged and analysis files are generated; and c) translation of certain data forms
      (mainly patient completed questionnaires) into French and Spanish. The
      involvement of three data centers provided a challenge in planning, designing and
      executing data management procedures in OPTIMA. Processes were implemented to
      ensure the trial's successful execution at the trinational level, without
      disregarding country-specific requirements and regulations. The OPTIMA model
      required a significant time and resource investment on behalf of all agencies
      involved, but allowed for autonomy and a sense of joint ownership of data in
      different countries.

PMID- 16279254
TI  - Small group processes relevant to data monitoring committees in controlled
      clinical trials: an overview of reviews.
AB  - BACKGROUND: The quality of the decisions reached by data monitoring committees
      (DMCs) is crucial. The aim of this paper is to identify factors that may make
      errors more or less likely in small, task-oriented, decision-making expert groups
      and to consider the implications of these factors for data monitoring committees.
      METHODS: A systematic overview was carried out of reviews of empirical studies of
      small group processes and decision errors in small, task-oriented decision-making
      groups in laboratory or real-world settings, published between 1950 and 2002 (n =
      57 included reviews). RESULTS: These reviews suggest that a number of factors may
      increase the likelihood that small groups will make poor and potentially
      erroneous decisions. The most important of these, in terms of empirical support,
      are: biased or overly directive leadership, expression of a limited range of
      opinions during group discussion, poor procedures for identifying or appraising
      the available information, and presentation of the available information in a way
      that is likely to result in biased perception of it. CONCLUSIONS: The main
      implications for DMCs relate to membership, the role of the chairperson, the
      information provided for DMCs and training for DMC members. Selection methods
      that encourage a degree of diversity within the DMC are recommended. Chairs of
      DMCs should be experienced members, who have the skills to facilitate a
      discussion, can manage conflict effectively and can be impartial. Adherence to a
      prespecified analysis plan is recommended to reduce the risk of error associated
      with strong evidence or excess information. Training in the use of methodical
      decision-making procedures, education about the factors that influence decision
      quality and an opportunity to participate in mock DMC discussions may be of
      benefit for new members.

PMID- 16279255
TI  - Covariate-based constrained randomization of group-randomized trials.
AB  - Group-randomized study designs are useful when individually randomized designs
      are either not possible, or will not be able to estimate the parameters of
      interest. Blocked and/or stratified (for example, pair-matched) designs have been
      used, and their properties statistically evaluated by many researchers. Group
      randomized trials often have small numbers of experimental units, and strong,
      geographically induced between-unit correlation, which increase the chance of
      obtaining a "bad" randomization outcome. This article describes a procedure-
      random selection from a list of acceptable allocations--to allocate treatment
      conditions in a way that ensures balance on relevant covariates. Numerous
      individual- and group-level covariates can be balanced using exact or caliper
      criteria. Simulation results indicate that this method has good frequency
      properties, but some care may be needed not to overly constrain the
      randomization. There is a trade-off between achieving good balance through a
      highly constrained design, and jeopardizing the appearance of impartiality of the
      investigator and potentially departing from the nominal Type I error.

PMID- 16279256
TI  - Bayesian estimation of vaccine efficacy.
AB  - Protective vaccine efficacy, VEs, is measured as one minus the incidence rate
      ratio (IRR) or the relative risk (RR) in the vaccinated group compared with the
      unvaccinated group. In this paper, we systematically present Bayesian estimation
      of protective vaccine efficacy based on the Poisson and binomial distributions.
      We also propose a new tool, the vaccine efficacy acceptability curve, to
      represent the uncertainty for the estimate of the vaccine efficacy graphically.
      It is very useful, especially when there is no universal agreement on the
      acceptable vaccine efficacy. The vaccine efficacy acceptability curve is defined
      as the posterior probability that the measure of vaccine efficacy VEs > or = k
      for each acceptable value k. When a vaccine is highly efficacious, the number of
      vaccinated susceptibles being infected is likely to be very small or even zero.
      Then the assumptions of normality and log-normality of IRR or RR usually do not
      hold well. Although frequentist exact methods provide good estimates of the
      confidence interval, they are overly conservative and are computationally
      difficult to extend to estimate the vaccine efficacy acceptability curve. In this
      paper, our focus is on Bayesian estimation of protective vaccine efficacy, its
      highest probability density credible set, and the vaccine efficacy acceptability
      curve through Markov chain Monte Carlo (MCMC) methods. We illustrate the methods
      using the data from two pertussis vaccine studies and the H. influenza Type B
      preventive trial.

PMID- 16279257
TI  - Factorial designs: a graphical aid for choosing study designs accounting for
      interaction.
AB  - The presence of possible treatment interaction when designing a factorial study
      can be either greeted with dismay (for an antagonistic or negative interaction)
      or can be welcome (in the case of a synergistic effect). The type of potential
      interaction may greatly influence the choice of study design. Depending on the
      magnitude of an expected additive or multiplicative interaction, a three-arm
      study, instead of a 2 x 2 factorial, may yield greater statistical power. A
      graphical aid for examining the loss of power due to the presence of such
      interaction is developed. The technique can also be applied to designing studies
      where prespecified subgroup analyses are of particular interest. Tests for
      interaction effects between subgroups are usually underpowered, even if the
      subgroups have been prespecified in the protocol. The technique can be used to
      determine the appropriate sample sizes in the subgroups to ensure adequate power
      to detect potential interaction effects. The method is illustrated with respect
      to a published 2 x 2 factorial study. In this study, interaction reduced the
      power of the final analysis to detect significant main effects.

PMID- 16279259
TI  - A reporting tool for real-time assessment of study data availability.
AB  - A simple framework for assessing and reporting data availability in an ongoing
      clinical trial is described. Protocol requirements, visit schedules and data
      availability are combined into a simple report to track the progress of a study.

PMID- 16279260
TI  - Eformoterol n-of-1 trials in chronic obstructive pulmonary disease poorly
      reversible to salbutamol.
AB  - AIMS: Benefits of long acting beta 2 agonists are unclear for severe chronic
      obstructive pulmonary disease (COPD) patients with poor response to short acting
      bronchodilators. We aimed to evaluate 1) effects of eformoterol in such patients
      using a 'n-of-1' double crossover study design, and 2) aggregate data as a double
      blind, double crossover randomized control trial. METHODS: Subjects with forced
      expiratory volume in one second (FEV1) < 60% predicted, and poor response to
      short acting bronchodilators were studied six times over 18 weeks. During that
      time they were prescribed four weeks of either eformoterol or placebo, followed
      by the alternate, and then a second crossover. Four-weekly measures included six
      minute walk distance (6MWD), FEV1, previous two weeks of symptoms, and chronic
      respiratory questionnaire (CRQ) including treatment goal items. RESULTS: Of 27
      original subjects (21 male, mean age of 70 years, five smokers, mean
      prebronchodilator FEV1 36% predicted), one subject had clinically significant
      concordant improvement in the CRQ dyspnoea domain and 6MWD (by 51 metres), but
      not for other outcomes. There were no concordant improvements in any other
      subjects. Aggregate double crossover data analysis demonstrated no improvement in
      any outcome measures. CONCLUSIONS: The 'n-of-1' study design and aggregate data
      analysis demonstrated lack of benefit from eformoterol in COPD patients with poor
      response to short acting bronchodilators.

PMID- 16279261
TI  - BMI and oral glucocorticoids as predictors of prognosis in COPD patients on long
      term oxygen therapy.
AB  - AIMS: The objectives of the study were to determine whether body mass index
      (BMI), and oral corticosteroid use predict survival and hospitalization in
      hypoxaemic chronic obstructive pulmonary disease (COPD) patients. METHODS: The
      study was a prospective cohort study with analysis of a nationwide database
      (Danish Oxygen Register). We studied survival and hospitalization in 221
      hypoxaemic COPD patients who were on long-term oxygen therapy (LTOT). RESULTS:
      Low BMI was strongly associated with high mortality (P < 0.001). Maintenance
      treatment with steroids was only associated with higher mortality in overweight
      patients (BMI > or = 25 kg/m2), RR = 3.8 (1.4-10.5), P = 0.011. Whereas BMI had
      no influence on risk of any hospitalization in patients using oral steroids, high
      BMI was independently associated with reduced risk of any hospitalization in
      patients without oral steroids [the RR of any hospitalization for each 1 kg/m2
      increase in BMI was 0.94 (CI: 0.90-0.99), P = 0.009]. Overall, the use of oral
      steroids was associated with increased risk of any hospitalization, RR = 1.7 (1.2
      2.4), P = 0.002. This increase was especially pronounced in the group with BMI
      above 25 kg/m2, where steroid treatment increased the risk of any hospitalization
      with RR = 3.6 (1.5-8.7), P = 0.005. CONCLUSIONS: In hypoxaemic patients on LTOT,
      low BMI is an independent risk factor of death and any hospitalization.
      Maintenance treatment with oral corticosteroids is associated with increased
      mortality and hospitalization in COPD patients with high BMI. Our findings
      suggest that loss of body weight should be avoided, and that oral corticosteroids
      should be used cautiously in patients on LTOT--especially those with high BMI.
      Further research on the role of changes in body composition as a prognostic
      factor is needed.

PMID- 16279262
TI  - Factors associated with prognosis in COPD: influence of body composition and
      systemic corticosteroid use on morbidity and mortality.

PMID- 16279263
TI  - Long-term continuous positive airway pressure (CPAP) outcomes from a sleep
      service using limited sleep studies and daycase CPAP titration in the management
      of obstructive sleep apnoea/hypopnoea syndrome.
AB  - BACKGROUND: Detailed polysomnography (PSG) and overnight continuous positive
      airway pressure (CPAP) titration as the basis for investigation and treatment of
      obstructive sleep apnoea/hypopnoea syndrome (OSAHS) incurs high costs from
      inpatient stays and technician attendance, even when split night studies are
      employed. Responding to rapidly increasing demand, from 1996 the sleep service at
      Glasgow Royal Infirmary adopted limited sleep studies and daycase CPAP titration
      as first line management. Here we describe the outcomes of this service between
      1996 and 1999. METHODS: Data were collected from prospective records made at
      follow up by sleep technicians and by casenote review. RESULTS: Results were
      available for 158 subjects (97.5%) of 162 commenced on CPAP during this period.
      One hundred and forty-eight (91%) were diagnosed by limited sleep studies and 80
      (50%) were diagnosed at home. The median follow up was 23 months (interquartile
      range (IQR), 13-35). Median use of CPAP in those continuing therapy was 5.3
      hours/night (IQR, 3.1 to 6.5) and 77% were still using CPAP at three years. Only
      initial low CPAP compliance (< 2 hours/night) significantly predicted early CPAP
      cessation. In those still on CPAP in 1999, the mean drop in Epworth Sleepiness
      Scale score was 4.6 points (95% confidence intervals, 3.2 to 6.0). CONCLUSION:
      These data from the CPAP population at Glasgow Royal Infirmary provide
      information on longterm outcomes using a diagnostic protocol based on limited
      sleep studies and daycase CPAP titration.

PMID- 16279264
TI  - A low-cost way to manage obstructive sleep apnea: does it pay?

PMID- 16279265
TI  - Training options: one size fits all?

PMID- 16279266
TI  - Performance enhancement in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Exercise limitation is a hallmark of chronic obstructive pulmonary
      disease (COPD) and is integral to the associated impaired health status of these
      patients. The poor exercise tolerance is multifactorial in origin, relating to
      airflow obstruction, disadvantageous lung mechanics, reduced oxygen delivery and
      skeletal muscle dysfunction. A number of interventions have been studied to
      determine whether they can impact on exercise performance. The most evidence
      based of these is exercise training, which along with other approaches, both
      previously investigated and putative, are discussed in this review.

PMID- 16279267
TI  - Short burst oxygen therapy is unhelpful?

PMID- 16279268
TI  - Short burst oxygen therapy is helpful?

PMID- 16279269
TI  - Genetics and the Dutch Hypothesis.
AB  - BACKGROUND: Increasingly, molecular genetic techniques are being used to improve
      our understanding of a number of common late onset complex disorders, such as
      hypertension, Alzheimer's disease and noninsulin dependent diabetes mellitus.
      Molecular genetic approaches have the potential to yield new information about
      disease pathogenesis that may be of great importance for the development of
      future treatments. AIMS: This review discusses the evidence for a genetic
      contribution to the development of chronic obstructive pulmonary disease (COPD)
      and specifically focuses on the hypothesis that asthma and COPD share some
      pathogenic mechanisms as originally proposed in 1960 in a theory that has since
      become known as the Dutch Hypothesis. In particular we will review the evidence
      from molecular genetics, both in support of and against the theory.

PMID- 16279271
TI  - The science of recruiting minority populations to screening trials.

PMID- 16279270
TI  - Withholding and withdrawing life prolonging treatment in the intensive care unit:
      a current European perspective.
AB  - BACKGROUND: Many deaths are now preceded by an end of life decision, particularly
      in the intensive care unit (ICU), but such practices vary considerably between
      countries, ICUs and individuals, depending on many factors including cultural and
      religious background, family and peer pressure and local practice. AIMS: In this
      review, we will discuss the application of the four key ethical principles-
      beneficence, nonmaleficence, autonomy and distributive justice--to
      withdrawing/withholding decisions. METHODS: Drawing data from several national
      and international studies, we then summarize the current situation across Europe
      regarding such practices before making some suggestions as to how we could
      facilitate the often difficult decision making process by improved communication
      between staff, patient and relatives.

PMID- 16279272
TI  - A randomized trial of recruitment methods for older African American men in the
      Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
AB  - BACKGROUND: Incidence rates for many types of cancer are higher among African
      American men than in the general population, yet African American men are less
      likely to participate in cancer screening trials. This paper describes the
      outcomes of a randomized trial (the AAMEN Project) designed to recruit African
      American men aged 55-74 years to a prostate, lung and colorectal cancer screening
      trial. METHODS: The recruitment interventions address four types of barriers to
      clinical trial participation: sociocultural barriers, economic barriers,
      individual barriers and barriers inherent in study design. Subjects were
      randomized to a control group or one of three increasingly intensive intervention
      arms, which used different combinations of mail, phone and in person church-based
      recruitment. RESULTS: Of the 39,432 African American men residing in the
      geographically defined study population (southeastern Michigan and northern
      Ohio), 17,770 men (45%) could be contacted, and 12,400 (31% of 39,432) were found
      to be eligible to participate. No statistically significant differences in age,
      education or income level were found among participants in the four study arms. A
      significantly greater enrollment yield (3.9%) was seen in the most intensive,
      church-based intervention arm, compared to the enrollment yields in the other two
      intervention arms (2.5 and 2.8%) or the control group (2.9%) (P < 0.01).
      CONCLUSIONS: The intervention that involved the highest rate of face-to-face
      contact with the study participants produced the highest enrollment yield, but
      several strategies that were thought could improve yield had no effect. These
      findings, which are consistent with current literature on population-based
      recruitment, should facilitate the development of future recruitment efforts
      involving older African American men.

PMID- 16279273
TI  - Nonparametric prediction of event times in randomized clinical trials.
AB  - In clinical trials with planned interim analysis, it can be valuable for
      logistical reasons to predict the times of landmark events such as the 50th and
      100th event. Bagiella and Heitjan (Stat Med 2001; 20: 2055-63) proposed a
      parametric prediction model for failure-time outcomes assuming exponential
      survival and Poisson enrollment. When little is known about the distributions of
      interest, there is concern that parametric prediction methods may be biased and
      inefficient if their underlying distributional assumptions are invalid. We
      propose nonparametric approaches to make point and interval predictions for
      landmark dates during the course of the trial. We obtain point predictions using
      the Kaplan-Meier estimator to extrapolate the survival probability into the
      future, selecting the time when the expected number of events is equal to the
      landmark number. To construct prediction intervals, we use a simulation strategy
      based on the Bayesian bootstrap. Monte Carlo results demonstrate the superiority
      of the nonparametric method when the assumptions underlying the parametric model
      are incorrect. We demonstrate the methods using data from a trial of
      immunotherapy of chronic granulomatous disease.

PMID- 16279258
TI  - Methodologic issues in terminating enrollment of a subgroup of patients in a
      multicenter randomized trial.
AB  - The National Emphysema Treatment Trial (NETT) was a multicenter randomized
      controlled trial comparing medical treatment plus lung-volume-reduction surgery
      (LVRS) to medical treatment alone for the treatment of severe emphysema. The
      primary outcomes specified for the trial were mortality from all causes and
      change in functional status as indicated by the change in maximum exercise
      capacity measured two years after randomization. A secondary objective of the
      trial was to define criteria to identify subgroups of patients at risk of harm or
      benefit from LVRS. Stopping guidelines for safety and efficacy based on 30-day
      mortality and a combination of overall mortality and functional status at two
      years were specified at the inception of the trial. Although specific subgroups
      of patients likely to benefit were not identified in advance, several clinical
      factors were specified as likely to be important in defining subgroups with
      differential outcome. In May 2001, with 40% of expected deaths accrued, the Data
      and Safety Monitoring Board determined that a subgroup of patients was at
      significantly higher risk of 30-day mortality from LVRS without counterbalancing
      evidence of functional benefit, and recommended that the protocol be modified to
      exclude further randomization of such patients. The trial's sponsor, the National
      Heart, Lung and Blood Institute, accepted the recommendation, which was rapidly
      communicated to participating clinics. This paper describes the operational
      aspects of identification of the subgroup and implementation of the
      recommendation to continue the trial, but to terminate enrollment of new patients
      in the subgroup. These aspects include notification of the investigators, the
      institutional review boards, the Research Group, the patients and the medical
      community. We also describe the repercussions of the publication and the
      misinterpretations of the results based on media coverage.

PMID- 16279274
TI  - Use of joint models to assess treatment effects on disease markers and clinical
      events: the Proscar Long-Term Efficacy and Safety Study (PLESS).
AB  - Clinical trials often collect longitudinal measurements of a disease marker and
      time to a major clinical event of the disease to assess treatment effects. It
      makes sense to combine the treatment effects on both the longitudinal disease
      marker and the time to clinical event, especially when the clinical event is also
      mediated through the disease marker over time. In this paper we apply a joint
      modeling approach in the assessment of the treatment effects in treating benign
      prostatic hyperplasia (BPH) for the Proscar Long-Term Efficacy and Safety Study
      (PLESS).

PMID- 16279275
TI  - Are missing outcome data adequately handled? A review of published randomized
      controlled trials in major medical journals.
AB  - BACKGROUND: Randomized controlled trials almost always have some individuals with
      missing outcomes. Inadequate handling of these missing data in the analysis can
      cause substantial bias in the treatment effect estimates. We examine how missing
      outcome data are handled in randomized controlled trials in order to assess
      whether adequate steps have been taken to reduce nonresponse bias and to identify
      ways to improve procedures for missing data. METHODS: We reviewed all randomized
      trials published between July and December 2001 in BMJ, JAMA, Lancet and New
      England Journal of Medicine, excluding trials in which the primary outcome was
      described as a time-to-event. We focused on trial designs, how missing outcome
      data were described and the statistical methods used to deal with the missing
      outcome data, including sensitivity analyses. RESULTS: We identified 71 trials of
      which 63 (89%) reported having partly missing outcome data: 13 trials had more
      than 20% of patients with missing outcomes. In 26 trials that measured the
      outcome at a single time point, 92% performed a complete case analysis and 8%
      imputed the missing outcomes using baseline values or the worst case value. In 37
      trials with repeated measures of the outcome, 46% performed complete case
      analyses, potentially excluding individuals with some follow-up data, while 14%
      performed a repeated measures analysis, 19% used the last observation carried
      forward, 11% imputed with the worst case value and 2% imputed using regression
      predictions. Thirteen (21%) of trials with missing data reported a sensitivity
      analysis. CONCLUSIONS: Our review shows that missing outcome data are a common
      problem in randomized controlled trials, and are often inadequately handled in
      the statistical analysis in the top tier medical journals. Authors should
      explicitly state the assumptions underlying the handling of the missing outcomes
      and justify them through data descriptions and sensitivity analyses.

PMID- 16279276
TI  - Time trends in personnel certification and turnover in the Collaborative Ocular
      Melanoma Study.
AB  - BACKGROUND: The purpose of this analysis was to examine and quantify the
      coordinating center workload in regard to certification and turnover of clinical
      personnel who participated in the Collaborative Ocular Melanoma Study (COMS).
      METHODS: The COMS was a set of multicenter, multidisciplinary randomized clinical
      trials conducted to evaluate radiotherapy for initial treatment of choroidal
      melanoma, a primary eye cancer. Patients were screened, enrolled, treated, and
      followed for mortality and clinical outcomes at 43 clinical centers in the United
      States and Canada, beginning late in 1986. Clinical centers were added to the
      COMS during three calendar periods. Training and certification of clinical
      personnel was performed by five resource centers and coordinated at the COMS
      coordinating center. A personnel database was maintained at the coordinating
      center for tracking certification progress, recertification, transfers and
      resignations. Certification records were analyzed for the period 1986 through
      1998 when patient accrual and treatment were completed. RESULTS: Clinical
      personnel (929 individuals) were certified for one or more of nine distinct roles
      in the COMS, resulting in 1,342 certifications; 26% were certified for two or
      more positions. The total number certified for each role ranged from 114 to 208.
      Certifications per year ranged from 260 in 1987 to 35 in 1997. The certification
      workload at the coordinating center rose following addition of each group of new
      clinical centers. It also increased in 1995 as a result of recertification of
      current personnel mandated by the external data monitoring committee.
      CONCLUSIONS: This analysis documented that training and certification were
      continuing tasks, and not limited to initiation of the study. Resignations and
      reassignments of certified personnel were responsible for 642 decertifications.

PMID- 16279277
TI  - Web-based communications and management of a multi-center clinical trial: the
      Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project.
AB  - While efficient methods of communication are known to be essential in conducting
      large multicenter clinical trials, very little information is provided on actual
      methods that can be implemented to improve communication. An integrated
      technology-based communication system was developed for the Sequenced Treatment
      Alternatives to Relieve Depression (STAR*D) project, which prospectively defines
      treatments that are most effective for participants with a diagnosis of a
      nonpsychotic major depressive disorder (MDD) who report an unsatisfactory
      clinical outcome to an initial and, if necessary, subsequent treatment(s). This
      web-based communication system is comprised of a multi-faceted study Web site,
      including a help desk, document sharing, a project directory and reports. In
      addition, automated reporting via e-mail and an online data correction mechanism
      are also available. The STAR*D communication system improves communication
      between study personnel and improves the quality of the study's data through the
      integration of system elements, the integration of those elements with
      traditional forms of communication,, by filling the gaps not addressed by those
      traditional methods and by reducing the staff workload burden.

PMID- 16279278
TI  - Optimizing clinical trial supply requirements: simulation of computer-controlled
      supply chain management.
AB  - BACKGROUND: Computer-controlled systems are commonly used in clinical trials to
      control dispensing and manage site inventories of trial supplies. Typically such
      systems are used with an interactive telephone or web system that provide an
      interface with the study site. Realizing the maximum savings in medication
      associated with this approach has, in the past, been problematic as it has been
      difficult to fully estimate medication requirements due to the complexities of
      these algorithms and the inherent variation in the clinical trial recruitment
      process. METHODS: We describe the traditional and automated methods of supplying
      sites. We detail a simulation approach that models the automated system. We
      design a number of simulation experiments using this model to investigate the
      supply strategy properties that influence medication overage and other strategy
      performance metrics. RESULTS: The computer-controlled medication system gave
      superior performance to the traditional method. In one example, a 75% overage of
      wasted medication in the traditional system was associated with higher supply
      failure than an automated system strategy with an overage of 47%. In a further
      example, we demonstrate that the impact of using a country stratified as opposed
      to site stratified scheme affects the number of deliveries and probability of
      supply failures more than the amount of drug wasted with respective increases of
      20, 2300 and 4%. Medication savings with automated systems are particularly
      significant in repeat dispensing designs. We show that the number of packs
      required can fall by as much as 50% if one uses a predictive medication
      algorithm. CONCLUSIONS: We conclude that a computer-controlled supply chain
      enables medication savings to be realized and that it is possible to quantify the
      distribution of these savings using a simulation model. The simulation model can
      be used to optimize the prestudy medication supply strategy and for midstudy
      monitoring using real-time data contained in the study database.

PMID- 16279279
TI  - The Society for Clinical Trials supports United States legislation mandating
      trials registration. Position paper.
AB  - The official position of the Society for Clinical Trials is to support
      legislation in the United States and internationally that mandates registration
      of all controlled clinicals trials at or before enrollment of the first
      participant. The major trial sponsor would be responsible for ensuring
      contribution of trial information. The mechanism for registering trials would be
      through research ethics review boards, and registration would be required for
      ethics approval and before trial initiation. Standardized data and a unique
      identification number would be available for each registered trial.

PMID- 16279280
TI  - Statistical evaluation of learning curve effects in surgical trials.
AB  - Randomized controlled trials (RCTs) in surgery have been impeded by concerns that
      improvements in the technical performance of a new technique over time (a
      "learning curve") may distort comparisons. The statistical assessment of learning
      curves in trials has received little attention. In this paper, we discuss what a
      learning curve effect is, the factors which effect it, how to display it, and how
      to incorporate the learning effect into the trial analysis. Bayesian hierarchical
      models are proposed to adjust the trial results for the existence of a learning
      curve effect. The implications for trial evaluation and data collection are
      considered.

PMID- 16279281
TI  - Statistical issues in multisite effectiveness trials: the case of brief strategic
      family therapy for adolescent drug abuse treatment.
AB  - The statistical development of the multisite Brief Strategic Family Therapy
      (BSFT) Trial of the National Institute on Drug Abuse's Clinical Trials Network
      provides a useful, real example of how an effectiveness trial can differ from an
      efficacy trial. In particular, two design elements distinguish this effectiveness
      trial from an efficacy trial. First, because the goal of the trial is to show
      that the use of BSFT would be an improvement on current practice, it was decided
      to compare BSFT to treatment as usual at each location. This decision ensures
      that the trial has the most ecological validity to the participating community
      treatment providers. Second, the desire to generalize the results to general
      clinical practice dictates that variability (in effect) across community
      treatment providers be estimated using a random effects model. These two
      decisions jointly influence the sample size calculations. Allowing variation in
      treatment as usual, will increase the variability in effect sizes across sites
      and estimation of this variability as a random effect necessitates a larger
      sample size (both number of community treatment providers and participants per
      community treatment provider), than is the case for a fixed site effect estimate.
      Details of these effects and their implications for the statistical design are
      presented.

PMID- 16279282
TI  - The Women's Health Initiative Study of Cognitive Aging (WHISCA): a randomized
      clinical trial of the effects of hormone therapy on age-associated cognitive
      decline.
AB  - The Women's Health Initiative Study of Cognitive Aging (WHISCA) was a two armed,
      randomized, placebo controlled, clinical trial designed to assess the efficacy of
      postmenopausal hormone therapy on age related changes in specific cognitive
      functions. WHISCA was an ancillary study to the Women's Health Initiative (WHI)
      and the WHI Memory Study (WHIMS) and enrolled 2302 women aged 66 to 84 years
      (mean 73.9; standard deviation 3.8) who did not meet criteria for dementia. Women
      were randomly assigned by the WHI to hormone treatment (unopposed conjugated
      estrogens (CEE) 0.625 mg/day if they were without a uterus; CEE combined with
      medroxyprogesterone acetate (MPA) 2.5 mg/day otherwise) or placebo for an average
      of three years before the first WHISCA assessment. WHISCA investigated the
      effects of hormone therapy on rates of change over time in memory, other aspects
      of cognition (language, attention, spatial ability), motor function, and mood. In
      this paper, we present the study rationale and design, including specific
      cognitive measures, and the challenges of incorporating WHISCA into an ongoing
      randomized trial. WHISCA provided a unique opportunity to investigate the
      potential of hormone therapy to modify age related changes in specific cognitive
      functions. WHISCA also demonstrated the feasibility of adding a detailed
      cognitive assessment into an ongoing clinical trial to address an important issue
      in women's health, despite the challenges of maintaining the integrity of the
      parent studies, ensuring high retention, and achieving high quality assurance
      across sites.

PMID- 16279283
TI  - Design and statistical issues in the homocysteinemia in kidney and end stage
      renal disease (HOST) study.
AB  - The Homocysteine Study (HOST) Veterans Affairs Cooperative Studies Program No.
      453, is a prospective, randomized, two arm, double blind study of patients with
      end stage renal disease (ESRD) or advanced chronic kidney disease (ACKD, defined
      as an estimated creatinine clearance of 30 ml/min or less). Its primary objective
      is to determine whether administration of high doses of three vitamins, folic
      acid, vitamin B6 and vitamin B12, to lower the high plasma homocysteine levels,
      will reduce all cause mortality. The secondary objectives are to examine whether
      the treatment lowers the incidence of myocardial infarction, stroke, amputation
      of a lower extremity, a composite of death and the foregoing three events, the
      plasma homocysteine level, and, in ESRD patients undergoing hemodialysis,
      thrombosis of the vascular access. A unique feature of this trial is that after
      initial evaluation at enrollment and one return visit the follow up is
      exclusively by phone (or, if necessary, by mail). The subject is contacted every
      three months throughout the duration of the study from a central location. The
      study drug is shipped to the patient from a central location rather supplied
      locally. In a two year enrollment period, 2006 patients are to be enrolled. The
      duration of the observation period is four to six years. Data will be stored and
      analyzed at a coordinating center. The study design has the power to detect a
      reduction in all cause mortality rate of 17%. Issues related to the unique
      features of the design of this study are discussed.

PMID- 16279284
TI  - Regulatory reforms and GCP clinical trials with new drugs in India.
AB  - Current Indian drug regulations do not allow for toxicology testing and clinical
      trials in India with compounds or molecules discovered abroad, except for
      treatments of tropical, cancer and cardiovascular diseases as part of global
      studies. The number of GCP Phase II/III trials by foreign sponsors has increased
      dramatically since 1995, attesting to the potential of India for lower cost
      trials and reduction in drug development costs and time, due to rapid patient
      recruitment. However, there have been problems with regard to intellectual
      property protection and adherence to informed consent guidelines. Starting in
      2005, a series of regulatory reforms and patent protection will be instituted
      that are designed to address many of these concerns; the nature of these reforms
      are presented and discussed. However, sponsors need to pay close attention to
      informed consent and other ethical issues in Indian trials, which enroll mainly
      poor and uneducated patients.

PMID- 16279285
TI  - An agenda for clinical trials: clinical trials in the genomic era.

PMID- 16279286
TI  - Dynamic treatment regimes.

PMID- 16279287
TI  - Lying, cheating and stealing in clinical research.

PMID- 16279288
TI  - The effect of correlation structure on treatment contrasts estimated from
      incomplete clinical trial data with likelihood-based repeated measures compared
      with last observation carried forward ANOVA.
AB  - Valid analyses of longitudinal data can be problematic, particularly when
      subjects dropout prior to completing the trial for reasons related to the
      outcome. Regulatory agencies often favor the last observation carried forward
      (LOCF) approach for imputing missing values in the primary analysis of clinical
      trials. However, recent evidence suggests that likelihood-based analyses
      developed under the missing at random framework provide viable alternatives. The
      within-subject error correlation structure is often the means by which such
      methods account for the bias from missing data. The objective of this study was
      to extend previous work that used only one correlation structure by including
      several common correlation structures in order to assess the effect of the
      correlation structure in the data, and how it is modeled, on Type I error rates
      and power from a likelihood-based repeated measures analysis (MMRM), using LOCF
      for comparison. Data from four realistic clinical trial scenarios were simulated
      using autoregressive, compound symmetric and unstructured correlation structures.
      When the correct correlation structure was fit, MMRM provided better control of
      Type I error and power than LOCF. Although misfitting the correlation structure
      in MMRM inflated Type I error and altered power, misfitting the structure was
      typically less deleterious than using LOCF. In fact, simply specifying an
      unstructured matrix for use in MMRM, regardless of the true correlation
      structure, yielded superior control of Type I error than LOCF in every scenario.
      The present and previous investigations have shown that the bias in LOCF is
      influenced by several factors and interactions between them. Hence, it is
      difficult to precisely anticipate the direction and magnitude of bias from LOCF
      in practical situations. However, in scenarios where the overall tendency is for
      patient improvement, LOCF tends to: 1) overestimate a drug's advantage when
      dropout is higher in the comparator and underestimate the advantage when dropout
      is lower in the comparator; 2) overestimate a drug's advantage when the advantage
      is maximum at intermediate time points and underestimate the advantage when the
      advantage increases over time; and 3) have a greater likelihood of overestimating
      a drug's advantage when the advantage is small. In scenarios in which the overall
      tendency is for patient worsening, the above biases are reversed. In the
      simulation scenarios considered in this study, which were patterned after acute
      phase neuropsychiatric clinical trials, the likelihood-based repeated measures
      approach, implemented with standard software, was more robust to the bias from
      missing data than LOCF, and choice of correlation structure was not an impediment
      to its implementation.

PMID- 16279290
TI  - Isotonic designs for phase I cancer clinical trials with multiple risk groups.
AB  - BACKGROUND: In phase I cancer clinical trials, adjustment for patient differences
      in toxicity susceptibility can be carried out with stratification into risk
      groups. Separate trials conducted for each risk group can lead to conflicting
      decisions, in which higher doses are recommended for higher risk groups. Designs
      which covariate adjust often require assumptions that clinicians may be
      uncomfortable with. METHODS: We extend up-and-down designs, isotonic designs and
      the continual reassessment method (CRM) to multiple risk groups with two-way
      isotonic regression. The only assumption about the groups is that they can be
      ordered according to their toxicity risk. The first two extensions, in
      particular, are nonparametric and easy for clinicians to understand. RESULTS:
      Simulations were based on an ongoing helical tomotherapy trial. Seven different
      toxicity scenarios were considered. The proposed methods compared favorably to a
      covariate adjusted CRM. The extended up-and-down designs inherited the
      conservativeness from the original designs. CONCLUSION: Our experience
      demonstrates that the escalation rules of multiple risk groups can be linked,
      without a parametric assumption about the group toxicity curve, to borrow
      strength and to ensure nonconflicting dosage recommendations.

PMID- 16279289
TI  - The effects of an open design on trial participant recruitment, compliance and
      retention--a randomized controlled trial comparison with a blinded, placebo
      controlled design.
AB  - BACKGROUND: In randomized trials there may be no overriding reason whether or not
      to have a placebo control. PURPOSE: We assessed the effects of an open trial
      design (no placebo and people know what tablets they are given) compared with a
      blinded, placebo-controlled design on recruitment, compliance and retention
      within a randomized trial of secondary osteoporotic fracture prevention. METHODS:
      We undertook a randomized controlled comparison nested within a placebo
      controlled trial of nutritional supplementation amongst people aged 70 years or
      over who had previously sustained a fracture, recruited in a UK teaching
      hospital. Randomization was 2:1 in favour of the blinded, placebo-controlled
      trial design. RESULTS: From 180 eligible participants randomized to receive
      information based on the open trial design, 134 (74.4%) consented to take part,
      compared with 233 (65.1%) of 358 people randomized to the blinded, placebo
      controlled design (difference 9.4%, 95% confidence interval 1.3-17.4%).
      Reluctance to take a placebo and the desire to know tablet allocation were
      reasons given for not taking part in the blinded, placebo-controlled design.
      There was no significant difference in tablet compliance. Open trial participants
      were more likely to remain in the trial for one year (difference 13.9%, 95%
      confidence interval 3.1-24.6%), mainly reflecting the high retention of the open
      trial no tablet group compared to the open trial tablet group (difference 23.6%,
      95% confidence interval 11.9-35.2%). The odds ratio for reporting an adverse
      event in the open trial compared to the blinded, placebo-controlled design was
      0.64 (95% confidence interval 0.28-1.49), and for reporting a fracture was 0.81
      (0.36-1.85). CONCLUSIONS: We conclude that using an open trial design may enhance
      participant recruitment and retention and thus improve generalizability and
      statistical power, but withdrawal rates may differ between the study allocations
      and may threaten the internal validity of the trial.

PMID- 16279291
TI  - ORI findings of scientific misconduct in clinical trials and publicly funded
      research, 1992-2002.
AB  - BACKGROUND: Since 1992 the Office of Research Integrity (ORI) had reviewed
      investigations of scientific misconduct in research funded by the US Public
      Health Service (PHS). ORI defined scientific misconduct as "fabrication,
      falsification, plagiarism, or other practices that seriously deviate from those
      that are commonly accepted within the scientific community for proposing,
      conducting, or reporting research". PURPOSE: The purpose of this study was to
      summarize the findings and administrative actions reported in ORI notices of
      scientific misconduct in clinical trials occurring between May 1992 and 2002.
      METHODS: Findings of misconduct were gathered from publicly available sources:
      the ORI annual reports and the NIH Guide to Grants and Contracts. RESULTS:
      Clinical trials accounted for 17 (13%) of the 136 investigations that resulted in
      findings of scientific misconduct, and they were noted in 12 (11%) of the 113
      brief reports of investigations closed with findings of no scientific misconduct.
      In clinical trials, the most severe sanction, debarment from US Government
      funding, was applied in six (35%) of the cases of misconduct compared to 79 (66%)
      of 119 cases from all other types of research combined. Of individuals cited for
      misconduct in clinical trials, three (18%) held doctorates in contrast to 81
      (68%) in other types of research. CONCLUSIONS: In clinical trials, junior
      employees may bear the burden of sanction for scientific misconduct. The most
      frequently applied sanction was the requirement that a plan of supervision of the
      sanctioned employees accompany any future application for funding which would
      include them. This imposition of sanction on an individual employee does not
      address possible causes of misconduct which may be inherent in the overall
      pattern of leadership, training and supervision in the trial. Furthermore, the
      definition of misconduct, as interpreted by the Departmental Appeals Board,
      excludes carelessness and other poor research practices that may lead to
      dissemination of more incorrect data than misconduct.

PMID- 16279292
TI  - Limited access data sets from studies funded by the National Heart, Lung, and
      Blood Institute.
AB  - The NHLBI has recently developed standards for protection of subject
      confidentiality which enable distribution of large data sets collected in
      completed epidemiological studies and clinical trials. This allows other
      investigators to pursue research using the data these studies have generated. An
      ethical commitment to protect the privacy of the research subjects requires
      careful review and some compromise in data details prior to distribution. To meet
      the challenge posed by the ethical and legal requirements to protect
      participants' privacy and making data sets useful for researchers, the NHLBI has
      devised a policy which seeks to balance these two opposing forces. This paper
      describes this policy as well as the limited access data sets currently available
      from NHLBI.

PMID- 16279293
TI  - Liability issues for data monitoring committee members.
AB  - In randomized clinical trials, a data monitoring committee (DMC) is often
      appointed to review interim data to determine whether there is early convincing
      evidence of intervention benefit, lack of benefit or harm to study participants.
      Because DMCs bear serious responsibility for participant safety, their members
      may be legally liable for their actions. Despite more than three decades of
      experiences with DMCs, the issues of liability and indemnification have yet to
      receive appropriate attention from either government or industry sponsors. In
      industry-sponsored trials, DMC members are usually asked to sign an agreement
      delineating their responsibilities and operating procedures. While these
      agreements may include language on indemnification, such language sometimes
      protects only the sponsor rather than the DMC members. In government-sponsored
      trials, there has been even less structure, since typically there are no signed
      agreements regarding DMC activities. This paper discusses these issues and
      suggests sample language for indemnification agreements to protect DMC members.
      This type of language should be included in DMC charters and in all consulting
      agreements signed by DMC members.

PMID- 16279295
TI  - Closing out a large clinical trial: lessons from the prospective study of
      pravastatin in the elderly at risk (PROSPER).
AB  - Relatively little has been written about the practicalities of the closeout of
      large, multi-centre clinical trials, but this aspect of trial conduct and design
      is both important and requires careful planning in order to be accomplished in a
      timely and orderly fashion. Here, we document our recent experiences of closing
      down the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). This
      five-year study with over 5800 subjects was closed down and published in 2002. We
      describe the methods used to ensure the speedy progression from the start of the
      closeout period through data lock to publication and presentation of the results.
      We discuss the strategic planning of all aspects of the closeout process, the
      training of staff for final visits, the methods used to follow-up all study
      participants including those used in dealing with "difficult to contact" and
      defaulted patients, and the strategies employed to ensure that study participants
      were left with positive feelings about the study. We also detail the methods
      employed to expedite the throughput of study paperwork and endpoints and the
      cleaning of data in preparation for data lock and subsequent publication and
      presentation of the results. Based on our experiences we summarize the most
      important aspects of closeout design and make recommendations for future studies,
      the most important of which is that a well-planned and well-managed closeout is a
      key feature of any large scale clinical trial and a coherent and practicable
      closeout strategy should be an integral part of the design.

PMID- 16279294
TI  - The Vermont Diabetes Information System (VDIS): study design and subject
      recruitment for a cluster randomized trial of a decision support system in a
      regional sample of primary care practices.
AB  - BACKGROUND: Despite evidence that optimal care for diabetes can result in reduced
      complications and improved economic outcomes, such care is often not achieved.
      The Vermont Diabetes Information System (VDIS) is a registry-based decision
      support and reminder system based on the Chronic Care Model and targeted to
      primary care physicians and their patients with diabetes. PURPOSE: To develop and
      evaluate a regional decision support system for patients with diabetes. METHODS:
      Randomized trial of an information system with clustering at the practice level.
      Ten percent random subsample of patients selected for a home interview. SUBJECT:
      and setting includes 10 hospitals, 121 primary care providers, and 7348 patients
      in 55 Vermont and New York primary care practices. RESULTS: We report on the
      study design and baseline characteristics of the population. Patients have a mean
      age of 63 years and a mean glycosolated hemoglobin A1C of 7.1 %. Sixty percent of
      the population has excellent glycemic control (A1 C < 7%); 45% have excellent
      lipid control (serum LDL-cholesterol <100 mg /dL and serum triglycerides <400
      mg/dL). Twenty-five percent have excellent blood pressure control (<130/80mmHg).
      These results compare favorably to recent national reports. However, only 8% are
      in optimal control for all three of hyperglycemia, lipids and blood pressure.
      CONCLUSIONS: Our experience to date indicates that a low cost decision support
      and information system based on the Chronic Care Model is feasible in primary
      care practices that lack sophisticated electronic information systems. VDIS is
      well accepted by patients, providers and laboratory staff. If proven beneficial
      in a rigorous, randomized, controlled evaluation, the intervention could be
      widely disseminated to practices across America and the world with a substantial
      impact on the outcomes and costs of diabetes. It could also be adapted to other
      chronic conditions. We anticipate the results of the study will be available in
      2006.

PMID- 16279296
TI  - The role of measurement reliability in clinical trials.
AB  - One of the principal characteristics of an outcome measure in a clinical trial,
      and any measurement in general, is its reliability. Reliability refers to the
      reproducibility of the measurement when repeated at random in the same subject or
      specimen. Reliability is often confused with validity, which refers to the extent
      to which the variable properly measures the underlying trait of interest. The
      coefficient of reliability is an estimate of the proportion of all variation that
      is not due to measurement error and is readily estimated from replicate
      measurements. The reliability of a measurement determines its maximal correlation
      or R2 and slope (or effect size) in regression models, its sensitivity and
      specificity when used for classifications or predictions, and the power of a
      statistical test employing the measurement. All decline as the reliability of the
      measure declines. The reliability of a measurement is an important consideration
      in the choice of the primary outcome measure for a clinical trial and in the
      choice of measures used for assessment of eligibility and exclusion. Reliability
      of measures should be assessed and assured by a quality control program based on
      randomly selected duplicate assessments. Just as the power of a study is reported
      in a final publication, so also should the reliability of the outcome and
      eligibility measurements so as to allow the authors to better describe, and
      readers to better understand, the sources of imprecision in study results, and
      those who follow to improve the design of future trials.

PMID- 16279297
TI  - Comparison of alternative estimation methods in confirmatory factor analyses of
      the General Health Questionnaire.
AB  - This paper examines the implications of violating assumptions concerning the
      continuity and distributional properties of data in establishing measurement
      models in social science research. The General Health Questionnaire-12 uses an
      ordinal response scale. Responses to the GHQ-12 from 201 Hong Kong immigrants on
      arrival in Australia showed that the data were not normally distributed. A series
      of confirmatory factor analyses using either a Pearson product-moment or a
      polychoric correlation input matrix and employing either maximum likelihood,
      weighted least squares or diagonally weighted least squares estimation methods
      were conducted on the data. The parameter estimates and goodness-of-fit
      statistics provided support for using polychoric correlations and diagonally
      weighted least squares estimation when analyzing ordinal, nonnormal data.

PMID- 16279298
TI  - Clark and Hatfield's evidence of women's low receptivity to male strangers'
      sexual offers revisited.
AB  - Although frequently cited, there has been no published scientific replication of
      Clark and Hatfield's (1989) and Clark's (1990) findings concerning women's low
      receptivity to male strangers' offers of casual sex. Consistently across three
      identically designed naturalistic experiments (aggregated N = 144), these authors
      reported a 0% acceptance rate by women. The present research analyzed an informal
      "real-life" journalistic project (N= 100) initiated by an Austrian magazine, in
      which results indicated a 6.1% acceptance rate (95% CI: 2.8-12.6%) for a complete
      stranger offering women immediate sexual involvement. Various contextual
      differences, such as setting, subjects' age and attractiveness, and age
      differences between requestor and receiver, probably contributed to the observed
      difference in outcome between the journalistic project and the original
      experiments. The present findings point to the importance of contextual effects
      in naturalistic investigations of women's receptivity to sexual offers.

PMID- 16279299
TI  - Death anxiety and death depression in Spanish nurses.
AB  - This study examined the dimensional structure of Tomas-Sabado and Gomez-Benito's
      Death Anxiety Inventory and Templer, et al.'s Death Depression Scale-Revised. The
      responses of 244 Spanish nurses to the Spanish forms of both scales were
      evaluated by means of a principal axis factor analysis with direct Oblimin
      rotation. Five significant factors were identified: Internally Generated Death
      Anxiety, Death Depression, Externally Generated Death Anxiety, Death Threat, and
      Death Sadness, accounting for 51.6% of the variance. The distribution of the
      factor loadings for the items of both scales on the five factors supported the
      discriminant validity of the constructs specific to each of the scales and
      justified their use in evaluating death anxiety and death depression
      independently.

PMID- 16279300
TI  - Educational attainment and suicide rates in the United States.
AB  - We examined the relationship between educational attainment and suicide rate in
      the United States for 2001. Suicide rates, adjusted for age, were compared with
      percentage of college graduates, median household income, and poverty in 50
      states in 2001. The correlations of suicide rates with educational attainment and
      median household income were both negative and statistically significant. Poverty
      was not significantly related to suicide rates. We concluded that higher
      education and income were associated with a decrease in suicide rates in 2001.
      Data from other years require examination for this conclusion to be
      generalizable.

PMID- 16279301
TI  - Implications of the United States census 2000 in analyzing and reporting new
      findings of disparities in health.
AB  - This paper argues that, when analyzing and reporting new findings of disparities
      in health, two areas from the recent U.S. Census of 2000 should be considered for
      those findings to be meaningful. The first is to avoid analyzing and reporting
      findings of disparity with an emphasis on the term "Hispanic" and instead to
      specify the particular Hispanic group from which such findings were collected,
      such as Mexican-American versus Cuban communities. The second point is that such
      findings should also take into consideration combination of two or more races.
      For example, reporting would allow for multiple groupings for respondents who
      consider themselves African American and White, or African American, Asian, and
      White.

PMID- 16279302
TI  - Evaluating psychometric properties of Farsi version of the Positive and Negative
      Perfectionism Scale.
AB  - This study examined the psychometric properties of the Farsi version of the
      Positive and Negative Perfectionism Scale. Two samples of 97 (56 women, 41 men)
      and 115 (67 women, 48 men) undergraduate students at the University of Tehran
      participated. Findings supported the internal consistency, test-retest
      reliability, concurrent validity, and factor structure of the Farsi version.
      Factor analysis provided evidence for two dimensions of perfectionism, Positive
      and Negative perfectionism. The two dimensions had significant negative and
      positive correlations, respectively, with measures of psychological distress and
      health, respectively. The Farsi version of the Positive and Negative
      Perfectionism Scale presented good psychometric properties for use in research.

PMID- 16279303
TI  - Re-using text from one's own previously published papers: an exploratory study of
      potential self-plagiarism.
AB  - A preliminary, two-part study explored the extent to which authors reuse portions
      of their own text from previously published papers. All 9 articles from a recent
      issue of a psychology journal were selected as target papers. Up to 3 of the most
      recent references cited in each of the target articles and written by the same
      authors were also obtained. All target articles and their corresponding
      references were stored digitally. Then, using specialized software, each
      reference was compared to its target article to assess the number of strings of
      text identical to both papers. Only one of the nine target articles reused
      significant amounts of text from one of its references. To explore further the
      possibility of additional text reuse, the references in each of the 9 sets of
      papers were compared against each other. The new comparison identified 5 pairs of
      papers with a substantial number of identical strings of text of 6 consecutive
      words in length or longer, but most of the reused text was confined to the Method
      section. The results suggest that some of these authors reuse their own text with
      some frequency, but this was largely confined to complex methodological
      descriptions of a research design and procedure.

PMID- 16279304
TI  - Willingness to seek help for psychosocial problems among Latino and white
      American college students.
AB  - This study compared 50 Latino and 50 White American students' perceptions of the
      severity of 25 psychological problems, their willingness to seek help for these
      problems, and their preferences for caregivers. Each group received a modified
      version of the Personal Problems Inventory. Latino students rated depression,
      financial concerns, and discrimination as more severe problems; their preference
      for mental health workers consistently significantly exceeded those of White
      students, although both groups preferred seeking help from family and community
      resources. Findings suggest the possibility of a greater role for therapists
      serving Latino students than currently exists.

PMID- 16279305
TI  - Mathematical background and attitudes toward statistics in a sample of Spanish
      college students.
AB  - To examine the relation of mathematical background and initial attitudes toward
      statistics of Spanish college students in social sciences the Survey of Attitudes
      Toward Statistics was given to 827 students. Multivariate analyses tested the
      effects of two indicators of mathematical background (amount of exposure and
      achievement in previous courses) on the four subscales. Analysis suggested grades
      in previous courses are more related to initial attitudes toward statistics than
      the number of mathematics courses taken. Mathematical background was related with
      students' affective responses to statistics but not with their valuing of
      statistics. Implications of possible research are discussed.

PMID- 16279306
TI  - Some neglected contributions of Wilhelm Wundt to the psychology of memory.
AB  - Wilhelm Wundt, whose name is rarely associated with the scientific study of
      memory, conducted a number of memory experiments that appear to have escaped the
      awareness of modern cognitive psychologists. Aspects of Wundt's system are
      reviewed, particularly with respect to his experimental work on memory. Wundt
      investigated phenomena that would fall under the modern headings of iconic
      memory, short-term memory, and the enactment and generation effects, but this
      research has been neglected. Revisiting the Wundtian perspective may provide
      insight into some of the reasons behind the historical course of memory research
      and in general into the progress of science in psychology.

PMID- 16279307
TI  - The "don't ask, don't tell" policy and military performance.
AB  - This paper is a response to Schumm's 2004 critique of Belkin's 2003 article,
      dealing with the "Don't Ask, Don't Tell" policy in the U.S. military. Schumm's
      critique specified four reasons for continuing to exclude homosexuals from
      military service: military effectiveness, sexual asymmetries, Christian soldiers'
      dilemma of "living a lie" and skewed opinions of policy makers and military
      elites. Each of these categories is analyzed and discussed.

PMID- 16279308
TI  - Breast cancer: a manual for a proposed group treatment integrating evidence based
      resilience factors.
AB  - The paper presents the structure and content of a manual for a proposed treatment
      of breast cancer patients in groups. The proposed treatment is structured, time
      limited, and integrates elements from 1995 work of Spiegel and the Yalom 1995
      theory of group therapy as well as empirically derived resilience factors.
      Addressing the psychological specificity of breast cancer, the overall treatment
      goals are to help patients to acquire new coping skills for relieving stress, to
      increase their personal and social competence and their use of available social
      support, to increase family coherence, to enhance optimism and quality of life,
      and to help patients develop new values and priorities that comply with their
      current and future life situation.

PMID- 16279309
TI  - Are employees' ratings of coworkers' organizational citizenship behavior
      influenced by their own perceptions of organizational justice?'.
AB  - Partial correlation analysis of questionnaire data from 62 of 65 employees of a
      Turkish company indicated that employees' own perceptions of organizational
      justice in terms of distributive, procedural, and interactional justice were
      related to how they rated their coworkers' organizational citizenship behavior.
      Specifically, all three two-way interactions between the justice variables were
      related to organizational citizenship behavior.

PMID- 16279311
TI  - Response to Skinner, et al. on "National personality characteristics: II.
      Adaption-innovation in Canadian, American, and British samples".
AB  - Skinner, et al. interpreted as significant the difference between means for
      Canadian men and women on Kirton's inventory and those for British and American
      samples. The means were similar to prior values. Skinner, et al.'s groups were
      large and composed of very unequal numbers of men and women, which factors could
      account for their interpretation. As reported, their analysis is insufficient to
      interpret very small mean variations as differences in national character.

PMID- 16279310
TI  - Quantitative and qualitative research in hypnosis: a commentary on Woodard.
AB  - In recent articles Woodard extended the Snygg and Combs theory of "Perceptually
      Oriented Hypnosis" to effect a rapprochement with a Phenomenology of Hypnosis.
      Both use the "Phenomenal Field" of consciousness, but they provide different
      interpretations and approaches to the essence of hypnosis. Snygg and Combs were
      heavily reliant on Gestalt psychology with a Cartesian dualism while
      Phenomenology maintains the unity of quality and quantity within consciousness.
      This commentary presents the philosophical basis for the two methods used to
      arrive at the essence of hypnosis in clinical practice.

PMID- 16279312
TI  - Test of the definition of learning disability based on the difference between IQ
      and achievement.
AB  - A learning disability is commonly defined as a discrepancy between IQ and
      achievement. This has been criticized for identifying too many children as having
      a learning disability who have high IQs and average academic achievement. Such
      overidentification as actually occurred was assessed in 473 referred children (8
      16 years, M= 10, SD=2) with normal intelligence. Learning disability was defined
      as a significant discrepancy (p<.05) between predicted and obtained achievement
      in reading, mathematics, or written expression on the Wechsler Individual
      Achievement Test. Predicted achievement was based on the child's WISC-III Full
      Scale IQ. Overidentification was considered to occur when a child scored at or
      above age level in reading, mathematics, and writing but still had a significant
      discrepancy between predicted and obtained achievement by virtue of a high IQ.
      Learning disability was diagnosed in 312 (66%) of the children. There was no
      overidentification because all children had one or more WIAT scores below the
      normative level for their age, i.e., < 100. Further, only 7% of the children were
      identified with a learning disability based on a WIAT score in the 90s. These
      children had a mean IQ of 123 and were rated by their teachers and parents as
      having learning problems.

PMID- 16279313
TI  - Addendum to concerns about professional schools.
AB  - The present research adds to the October 2004 comments in the American
      Psychologist of Templer and Arikawa who reported that traditional clinical
      psychology graduate students had greatly higher mean GRE scores than professional
      school students. The traditional and professional students had mean undergraduate
      GPAs of 3.62 (SD= .13) and 3.36 (SD= .14), respectively. The mean respective
      percentages of applicants to 148 traditional and 50 professional programs
      accepted were 10.4 (SD= 9.5) and 44.4 (SD= 19.5), respectively.

PMID- 16279315
TI  - Factorial structure of short scales measuring manic-depression in Kuwaiti
      undergraduates.
AB  - A sample of 202 Kuwaiti college students (63 men and 139 women; Mage=21.6 yr.,
      SD=2.4) responded to the Thalbourne, et al.'s Manic-Depressiveness Scale. In a
      factor analysis with a varimax rotation, 14 of 18 items had significant loadings
      (>.3) on the first factor, including 8 items of the original depression scale. 6
      items significantly loaded on the second factor, including 3 items of the
      original mania scale. This did not match the hypothetical structure of the scale.

PMID- 16279314
TI  - Social dominance orientation and opinions about what is America's most serious
      social problem.
AB  - This study tested whether a measure of Social Dominance Orientation was
      associated with opinions about America's most serious social problem. 150
      undergraduates enrolled in social problems classes responded to the 14-item scale
      and to an open-ended question, "In your opinion, what is the most serious social
      problem in our country today?". Analysis shows that mean scale scores differed
      significantly across social problem responses. Correspondence analysis, plotting
      association between scale scores and social problem responses, was interpreted as
      support for social dominance theory. Higher scale scores were associated with
      problems of crime and negative values and lower scores with problems of education
      and racism.

PMID- 16279316
TI  - Using a paired-associate learning task to assess parent-child phenotypic
      similarity.
AB  - The fact of uncertain paternity has led some researchers to hypothesize that
      children should more closely resemble their fathers than their mothers. The
      evidence in support of this hypothesis is mixed, partly because the procedures
      used to measure perceived phenotypic similarity may not be sensitive enough to
      detect small effects and partly because comparisons are made between fathers and
      mothers rather than random control groups. In the present experiment the
      viability of using a paired-associate learning paradigm to investigate parent
      child phenotypic similarity is demonstrated using 15 stimulus sets of colored
      photographs picturing two adults and one child. Using a 2 x 2 between subjects
      analysis of variance for total errors across learning trials, evidence indicated
      genetic relatedness for both mothers and fathers influences perceived resemblance
      and that association of male facial features with those of children, whether
      paternal or not, are learned more quickly than female facial features. While the
      significance of genetic relatedness to facial similarity was expected, the
      overall sex difference was not. However, the additive combination of these
      variables, genetic relatedness and maleness may explain why children seem to more
      closely resemble their fathers.

PMID- 16279317
TI  - Death obsession in Arabic and Western countries.
AB  - The current investigation compared a measure of death obsession among 1,853
      volunteer undergraduates from four Arab countries (Egypt, Kuwait, Lebanon, and
      Syria) with 791 from three Western countries, i.e., Britain, Spain, and the USA.
      Comparable Arabic, Spanish, and English versions of the Death Obsession Scale
      were used. The mean scores on death obsession for the Arabic participants were
      higher than those of their Western counterparts for both men and women.

PMID- 16279318
TI  - Perceptually oriented hypnosis: cross-cultural perspectives.
AB  - Literature is reviewed and summarized relevant to present cross-cultural,
      shamanic, and spiritual aspects of hypnosis. Explanations are offered within the
      framework of Woodard's theory of Perceptually Oriented Hypnosis. Research on
      cross-cultural aspects of hypnosis could enhance understanding of
      phenomenological and perceptual aspects of hypnosis, increase knowledge of
      hypnotic phenomena, and expand understanding of perceptual awareness. A summary
      of the qualitative research methodologies to enhance understanding of
      multicultural hypnotic experiences is presented. This groundwork provides for
      further exploration of cross-cultural hypnosis. Surprisingly, some suggestions
      have remained underutilized or not published.

PMID- 16279319
TI  - Comment on McCall, Trombetta, and Gipe's 2004 proposed impression management
      explanation for the credit card effect.
AB  - There is a dearth of empirically supported theoretical explanation since its
      introduction; Feinberg's 1986 credit card effect showed greater product
      valuations and donation intentions by experimental participants when asked to
      make such estimates in the presence of credit card stimuli. This comment on
      McCall, Trombetta, and Gipe (2004) notes potential flaws and adjudged over
      interpretation of results in their attempt to replicate successfully and derive
      theoretical explanation for the credit card effect.

PMID- 16279320
TI  - Validity and reliability of the audit and CAGE-AID in Northern Plains American
      Indians.
AB  - According to the Indian Health Service, substance abuse and Type 2 diabetes are
      serious problems among Native Americans. To assess substance use in a medical
      setting, valid screening tests are needed so the Alcohol Use Disorders
      Identification Test (AUDIT), a simple brief screen for excessive drinking, and
      the CAGE-adapted to Include Drugs (CAGE-AID) for identifying primary care
      patients with alcohol and drug disorders were given 50 Northern Plains American
      Indians with diabetes. Both are short, easy to administer, have good sensitivity
      and specificity, and can be easily incorporated into a medical history protocol
      or intake procedure. Reliability coefficients were above .90 and appeared to have
      sufficient concurrent and divergent validity indicated by moderate correlations
      with the General Well-being Schedule (rs=-.39 and -.36), the Family-Adaptation,
      Partnership, Growth, Affection, & Resolve (r =-.47 and -.36), and the Beck
      Depression Inventory-IT (r = .36 and .29).

PMID- 16279321
TI  - Humor and gender roles: does age make a difference?
AB  - Crawford's analysis in 2003 suggests that humor interacts with gender so that
      traditional social norms of femininity and masculinity may be reinforced or
      diinished. Yet age as a covariate was not considered. Assessment of the attitudes
      toward humor among 72 older women (M=72.0, SD=9.8, range=51-93 years) and 24
      older men (M=69.8, SD=6.8, range=59-90 years) in 1996 by Vitulli and Parman
      suggest ratings on a Likert-type scale (anchored by 5: strongly agree and 1:
      strongly disagree) in which humor and gender interact. Moreover, a post hoc
      Scheffe test showed a significant sex effect on the female-oriented scale. Older
      women perceived humor as an important quality for women, whereas older men did
      not. Generational differences among studies on humor and sex underscore the need
      for contemporary research inclusive of age measures.

PMID- 16279322
TI  - Long term symptoms and limitations of activity of people with traumatic brain
      injury: a ten-year follow-up.
AB  - This study examined the effect of Traumatic Brain Injury 10 years post-injury.
      Frequencies of head injury symptoms and activity limitation by level of severity
      were measured in a consecutive series of 61 adults who were admitted to a
      tertiary-care center for traumatic brain injury. Irritability and Anxiety were
      the most frequently reported symptoms from the Head Injury Symptom Checklist.
      Bothered by noise and Bothered by light were the least frequently reported.
      Trouble hearing what is said in a group conversation and Trouble hearing what is
      said in a one-to-one conversation were the most commonly reported limitations of
      activity from the Health and Activity Limitations Survey. Overall, this study
      illustrates that symptoms remain many years following brain injury, irrespective
      of the injury's severity.

PMID- 16279323
TI  - Eysenck Personality Questionnaire scales and paper-and-pencil tests related to
      creativity.
AB  - Pearson correlations for scores on scales of the 1975 version of the Eysenck
      Personality Questionnaire with measures of schizotypy, hypomania, and creative
      traits are reported for 625 undergraduates. The Psychoticism scores are
      correlated .30 with Hypomanic traits, .25 with Perceptual Aberration, and .20
      with the How Do You Think, a test of attitudes and activities related to
      creativity. Extraversion is also related to creativity-relevant scores. Results
      support a broad and nonspecific role for the Psychoticism scale in relation to
      both creativity and subclinical symptomatology.

PMID- 16279324
TI  - Sex- and age-related differences in mathematics.
AB  - This study examined sex differences and age-related changes in mathematics based
      on Eccles's 1985 expectancy-value model of "achievement-related choices" and
      Dweck's 1986 motivation-process model. We have assessed motivational variables
      and performance in mathematics for youth in Grades 5, 7, and 9 in a German
      comprehensive secondary school. Significant sex differences in Grades 7 and 9
      were observed even when school marks were controlled for. Furthermore, the
      results indicated differences between Grade 7 and Grade 9 on most of the
      motivational variables. Older students show a less favorable motivational
      pattern. Our results give evidence of the importance of motivational
      encouragement in mathematics classes, especially for girls and low achieving
      learners.

PMID- 16279325
TI  - Short form of Sarason's Social Support Questionnaire: French adaptation and
      validation.
AB  - The original short form of Sarason's Social Support Questionnaire measures two
      dimensions of social support, availability and satisfaction. The factorial
      structure of the social support was assessed in a French sample along with the
      association between the dimensions of social support and personality traits such
      as Extraversion, Neuroticism, and Depression. A 6-item French version was
      administered to 648 subjects: 348 university freshmen (228 females, 120 males)
      and 304 unemployed men. A principal component analysis followed by oblique
      rotations was undertaken on each sample. This yielded two factors, Availability
      and Satisfaction. These results sustained the stability of the factorial
      structure from one culture to another. Validity and reliability were
      satisfactory. Moreover, these two dimensions were correlated with two personality
      scales (high extraversion, low depression). Such results agree with previous
      results establishing relations between social support and salutogenic dimensions
      of personality.

PMID- 16279326
TI  - Relation of urinary incontinence, menopausal symptoms, and life satisfaction in
      middle-age Korean women.
AB  - Associations of urinary incontinence, menopausal symptoms and life satisfaction
      of 235 middle-age Korean women (40 to 59 years) were investigated, based on
      responses to a self-report questionnaire. Urinary incontinence was positively
      correlated with menopausal symptoms (r =.24) and negatively correlated with life
      satisfaction (r=-.11). Life satisfaction was negatively correlated with
      menopausal symptoms (r = -.28). All rs indicate weak associations and account for
      small common variables. Even so, results suggest effective treatment of urinary
      incontinence and menopausal symptoms could enhance life satisfaction through
      promoting healthy behavior and emotional health in such middle-age women.

PMID- 16279327
TI  - Competitiveness among Japanese, Chinese, and American undergraduate students.
AB  - Although research indicates that competitiveness, defined as the desire to win in
      interpersonal situations, is an important individual difference that influences a
      range of social interactions, little research has focused on competitiveness in
      cultures outside the United States. This study investigated competitiveness in
      three cultures by comparing Chinese (n=61), Japanese (n=232), and American
      (n=161) undergraduate college students. Nationality and sex were compared on two
      scales of the revised Competitiveness Index. Analysis indicated that American
      students scored higher on Enjoyment of Competitiveness than Chinese and Japanese
      students, but no difference was found on Contentiousness. Men scored higher than
      women on Enjoyment of Competition but not on Contentiousness. The findings
      indicate that sex and cultural patterns influence some but not all aspects of
      competitiveness.

PMID- 16279328
TI  - Tobacco and alcohol tax relationships with suicide in Switzerland.
AB  - Previous research has shown an empirical link between tobacco and alcohol use and
      suicide. If tobacco and alcohol use contribute to suicidal behaviors, then
      policies designed to reduce the tobacco and alcohol consumption may succeed in
      reducing suicides as well. To test this hypothesis, correlations for suicide
      rates with alcohol consumption, taxes on alcohol and tobacco in Switzerland were
      examined using sets of time-series data from Switzerland in 1965-1994. The tax on
      tobacco correlated significantly negatively with male standardized suicide rate.
      The tax on alcohol also correlated significantly with male standardized suicide
      rate in an autoregressive model. On the other hand, significant relationships
      with female suicide rate were not found. Policies designed to reduce tobacco
      consumption are consistent with a benefit of reducing suicides, particularly for
      men in this sample.

PMID- 16279329
TI  - Psychometric properties of the Trauma Stages of Recovery.
AB  - Of the trauma theories available, Herman's has captured the essential features
      common to most traumatic etiologies. Continued development of this theory has
      included dimensions within stages of recovery. The Trauma States of Recovery is
      presented here as a way of assessing stages of recovery and inherent components.
      Three samples of about 500 college students each and a clinical sample (n=34)
      were recruited. Independent principal components analyses, employing a scree
      plot, gave a five-component solution accounting for 40.2% of the total variance.
      The component solution employed Promax rotation for the correlated components.
      The five components were named Emotional Awareness and Control, Symptom Mastery,
      Coping, Memory, and Relationships. Internal consistencies, test-retest
      reliability, and split-half reliability were acceptable. Response bias was low.
      Convergent validity (with various subscales from the Beck Depression Inventory,
      the Self-esteem Scale, the Spielberger Anger-Expression Scale, and the
      Dissociative Experiences Scale) and discriminant validity (with various subscales
      of the AIDS Knowledge and Attitudes Survey and Jackson's Personality Research
      Form Dominance Scale) were promising. The Trauma Stages of Recovery also
      significantly discriminated between clinical and nonclinical samples on three of
      the five components, Symptom Mastery, Coping, and Memory.

PMID- 16279330
TI  - Sensation seeking and the use and selection of media materials.
AB  - 175 individuals recruited from urban universities (n=82) and the surrounding
      community (120 women, 55 men; 82 18- to 25-yr.-olds, 26 26- to 34-yr.-olds, 44 35
      to 50-yr.-olds, 23 50 yr. old or over) completed a sensation seeking scale and
      measures of the frequency with which they used specific media and selected
      specific television programming, film, and music genres. Regression analyses
      showed Sensation Seeking to be associated positively with Movie Theatre
      Attendance and with the Selection of Urban Music Genres. Sensation Seeking was
      also associated negatively with Selection of Light Film Genres.

PMID- 16279331
TI  - Pervasive developmental disorders rating scale: development and construct
      validity.
AB  - The Pervasive Developmental Disorders Rating Scale was designed for use in
      screening of pervasive developmental disorders. This paper describes the
      rationale and development of the scale and assesses its construct validity with
      ratings from a sample of 362 children ranging in age from 1 to 12 years and
      diagnosed with autistic disorder. The hypothesized heirarchical factor model and
      two competing models were examined through confirmatory factor analysis. The
      analysis supported the factor structure of the hypothesized model in this
      particular sample of children with autistic disorder. Limitations and areas for
      research are discussed.

PMID- 16279332
TI  - College students' acceptance of potential treatments for ADHD.
AB  - The purpose of the current study was to investigate the influence that the
      professional occupation of a consultant making a treatment recommendation may
      have on college students' (82 women and 52 men) acceptance of a proposed
      treatment for a child displaying characteristics of Attention
      Deficit/Hyperactivity Disorder. Consultants were special education teachers,
      school psychologists, or physicians. The study also examined college students'
      ratings of treatment acceptability associated with three frequently implemented
      interventions of either nonspecific medication, token economy with response cost,
      or time-out for children with characteristics of Attention Deficit/Hyperactivity
      Disorder. Analysis indicated college students found a token economy intervention
      was the least acceptable recommendation by a physician.

PMID- 16279333
TI  - Effects of receptive listening on the congruence of speakers' response latencies
      in dialogues.
AB  - The present study investigated the receptiveness of speakers toward
      conversational partners in dialogues by comparing duration of response latencies
      in both Compromise and Debate conditions. 12 dyads of speakers holding opposing
      opinions participated in a 15-min. dialogue. Six dyads in the Compromise
      condition reached a conclusion through discussion and consideration of the
      partner's opinion. The six dyads in the Debate condition imposed their opinion on
      the conversational partner. Analysis indicated that in compromise dialogues, the
      response latencies of the conversational partners become similar over the time
      course, while in debate diaogues, the response latency does not become similar,
      suggesting that speakers having a receptive attitude adjust their response
      latencies to match the partner's. The role of congruence of response latencies in
      dyadic communication was discussed.

PMID- 16279335
TI  - Increasing differentiation of women and men: gender trait analysis 1974-1997.
AB  - Analysis of the responses of some 4,000 college students showed increasing
      differentiation in the ratings of gender characteristics of typical women and
      men, especially with regard to feminine traits. Roughly similar patterns were
      observed in five other studies using the same gender traits. All studies showed
      continued or increased sex typing on affectionate and sympathetic. In the present
      study women became more feminine, and males became less, on all but one of the
      feminine traits. This increasing differentiation of women and men is not
      consistent with predictions from the sociocultural model; they are more
      consistent with those of the evolutionary model.

PMID- 16279334
TI  - Sample homogeneity and coefficient alpha: comment on MJI and Alkhateeb's
      reliability generalization study and a theoretical clarification.
AB  - Reliability generalization studies are increasingly frequently reported in the
      literature, including Mji and Alkhateeb's 2005 study of the Conceptions of
      Mathematics Questionnaire. The present article comments on an issue of
      reliability generalization as used in that study and clarifies a theoretical
      point regarding the meaning of coefficient alpha and what data features tend to
      influence it as a measure of score reliability.

PMID- 16279336
TI  - The General Health Questionnaire and Eysenck's three-dimensional model of
      personality.
AB  - A sample of 115 men and women between the ages of 20 and 60 completed the 30-item
      General Health Questionnaire together with the short-form Revised Eysenck
      Personality Questionnaire. The data indicate psychological distress so assessed
      is correlated .43 (p <.001) with Neuroticism and -.26 (p <.01) with Introversion
      but is unrelated to Psychoticism scores.

PMID- 16279337
TI  - Note on Korbanka and Gaede's MMPI-2 scale of history of emotional abuse.
AB  - Korbanka and Gaede recently developed an MMPI-2 scale by discriminant analysis to
      identify people who were emotionally abused in childhood or adolescence. The
      scale had an exceptionally high classification rate in the initial sample of
      mental health outpatients, and the authors recommended that it be validated in
      other samples. This note reinforces the recommendation for cross-validation,
      examines item overlap with other scales, shows emotionally abused patients
      responded to many items more positively and with more favorable self-description
      than emotionally unabused patients, and comments on the method used to develop
      the scale.

PMID- 16279338
TI  - Utility of the impact of event scale in screening for posttraumatic stress
      disorder.
AB  - This study assesses the optimal cut-off point for the Impact of Event Scale and
      compares its screening properties with those of the Self-rating Inventory for
      Posttraumatic Stress Disorder among war-related trauma victims. 74 patients with
      war-related trauma were administered the Impact of Event Scale and the Self
      rating Inventory for Posttraumatic Stress Disorder, followed 1 wk. later by the
      Clinician-administered PTSD Scale. Receiver operating characteristic analysis
      indicated for the Impact of Event Scale a sensitivity of .77 and a specificity of
      .51 at a cut-off value of 36. For the Self-rating Inventory for Posttraumatic
      Stress Disorder a sensitivity of .86 and a specificity of .69 were found at a cut
      off value of 52. The authors conclude that careful use of the Impact of Event
      Scale as a screening measure for Posttraumatic Stress Disorder is warranted.

PMID- 16279339
TI  - Dimensionality and construct validity of a video-based, objective personality
      test for the assessment of willingness to take risks in road traffic.
AB  - The study at hand reports first results about the dimensionality and construct
      validity of a newly developed objective, video-based personality test, which
      assesses the willingness to take risks in traffic situations. On the basis of the
      theory of risk homeostasis developed by Wilde, different traffic situations with
      varying amounts of objective danger were filmed. These situations mainly
      consisted of situations with passing maneuvers and speed choice or traffic
      situations at intersections. Each of these traffic situations describes an action
      which should be carried out. The videos of the traffic situations are presented
      twice. Before the first presentation, a short written explanation of the
      preceding traffic situation and a situation-contingent reaction is provided. The
      respondents are allowed to obtain an overview of the given situations during the
      first presentation of each traffic situation. During the second presentation the
      respondents are asked to indicate at which point the action that is contingent on
      the described situation will become too dangerous to carry out. Latencies for
      items were recorded as a measure for the magnitude of the person's subjectively
      accepted willingness to take risks in the sense of the risk homeostasis theory by
      Wilde. In a study with 243 people with different education and sex, the one
      dimensionality of the test corresponding to the latency model by Scheiblechner
      was investigated. Analysis indicated that the new measure assesses a one
      dimensional latent personality trait which can be interpreted as subjectively
      accepted amount of risk (target risk value). First indicators for the construct
      validity of the test are given by a significant correlation with the construct
      related secondary scale, adventurousness of the Eysenck Personality Profiler
      with, at the same time, nonsignificant correlations to the two secondary scales,
      extroversion and emotional stability, that are not linked to the construct.

PMID- 16279340
TI  - Internal consistency reliability of the Francis Scale of Attitude toward Alcohol
      among adolescents in Northern Ireland.
AB  - The Francis Scale of Attitude toward Alcohol was completed by 324 adolescents (M=
      17.1 yr., SD=3.6) in Northern Ireland to examine reliability of the measure among
      this age group. These data support its internal consistency (.89) and suggest
      that the Francis Scale of Attitude toward Alcohol is psychometrically appropriate
      for use among this age group.

PMID- 16279342
TI  - Confirmatory factor analysis of the eating disorder inventory.
AB  - The Japanese version of the Eating Disorder Inventory was completed by 204 female
      university students. Confirmatory factor analyses supported the 9 factors
      reported by Shimura, et al. (2003). Further, maximum likelihood factor analysis
      yielded nine factors, accounting for 48.8% of the total variance. There was also
      adequate fit for each of the 9 subscales. This study provided additional evidence
      on validity for this Japanese version.

PMID- 16279341
TI  - Exploring high school science students' perceptions of parental involvement in
      their education.
AB  - This exploratory study describes high school students' perceptions of their
      parents' involvement in their education and in relation to school achievement. A
      new 12-item Parental Involvement Scale was used to measure parents' involvement
      in curricular and extracurricular activities and using exploratory analyses to
      estimate the scale's properties. Exploratory analysis resulted in the reduction
      of the 12 items to 8, with an internal consistency (Cronbach alpha) .82. Grade 12
      science students indicated that their less educated parents were involved in
      activities pertaining to their learning; however, high perceived parental
      involvement in curricular activities was related to low achievement. It is
      recommended that further exploratory analyses be undertaken to examine the
      reported two-dimensional model of the Parental Involvement Scale.

PMID- 16279343
TI  - Opening access to physicians wins dollar 1.2M performance bonus.

PMID- 16279344
TI  - Sharing gains with physicians may be legally possible.
AB  - Hospitals that would like to pay physicians to encourage them to find more cost
      effective ways of delivering care have a new tool at their disposal: Gainsharing
      agreements.

PMID- 16279345
TI  - Population management software improves physician performance.
AB  - After eight years of using electronic medical records, one physician group found
      that its performance on certain measures was no better than practices still using
      paper records, until they added population management software.

PMID- 16279346
TI  - Rapid ED access reduces patients leaving without being seen.
AB  - Implementing a brief sign-in process for emergency department patients, and
      completing full registration later at the bedside, has allowed the University of
      California, San Diego Medical Center to eliminate a major patient flow
      bottleneck.

PMID- 16279347
TI  - Hospitals open cardiac clinics to improve care for women.
AB  - Responding to studies that show women are more likely to die from heart disease
      than men, hospitals around the country are opening specialized heart clinics to
      improve treatment of heart disease in women.

PMID- 16279348
TI  - Why do some CPOEs work while others flounder?
AB  - When groups from other hospitals come to see the acclaimed computerized physician
      order entry system (CPOE) at Alamance Regional Medical Center, it's not that hard
      to tell who will have problems with their own CPOE project.

PMID- 16279349
TI  - Tests for equivalence based on odds ratio for matched-pair design.
AB  - Currently, methods for evaluation of equivalence under a matched-pair design use
      either difference in proportions or relative risk as measures of risk
      association. However, these measures of association are only for cross-sectional
      studies or prospective investigations, such as clinical trials and they cannot be
      applied to retrospective research such as case-control studies. As a result,
      under a matched-pair design, we propose the use of the conditional odds ratio for
      assessment of equivalence in both prospective and retrospective research. We
      suggest the use of the asymptotic confidence interval of the conditional odds
      ratio for evaluation of equivalence. In addition, a score test based on the
      restricted maximum likelihood estimator (RMLE) is derived to test the hypothesis
      of equivalence under a matched-pair design. On the other hand, a sample size
      formula is also provided. A simulation study was conducted to empirically
      investigate the size and power of the proposed procedures. Simulation results
      show that the score test not only adequately controls the Type I error but it can
      also provide sufficient power. A numerical example illustrates the proposed
      methods.

PMID- 16279350
TI  - Estimation of cancer drug potencies and relative potencies from in vitro data.
AB  - A method is proposed for the estimation of drug or toxicity potencies using in
      vitro data. A typical experiment in cancer research is presented where cells from
      a tumor-derived cell line were deposited as fixed volumes in 12-well cell culture
      plates. After waiting for 72 hours (for further growth), the wells were exposed
      to different concentrations of a drug and, at the end of the experiment, the
      numbers of surviving cells were counted. In this article, the "standard model" is
      extended to take explicit account of the error structure generated by the two
      experimental stages, namely, the cell deposition stage (and growth, prior to
      challenging by drug) and the cell counting stage (by hemacytometer) that are
      fundamental to the design but have usually been ignored in the modeling process.
      A simulation study illustrates substantial gains in efficiency in the estimation
      of the median effective dose.

PMID- 16279351
TI  - Assessment of equivalence using a concordance correlation coefficient in a
      repeated measurements design.
AB  - Some assay validation studies are conducted to assess agreement between repeated,
      paired continuous data measured on the same subject with different measurement
      systems. The goal of these studies is to show that there is an acceptable level
      of agreement between the measurement systems. Equivalence testing is a reasonable
      approach in assay validation. In this article, we use an equivalence-testing
      criterion based on a decomposition of a concordance correlation coefficient
      proposed by Lin (1989, 1992). Using a variance components approach, we develop
      bounds for conducting statistical tests using the proposed equivalence criterion.
      We conduct a simulation study to assess the performance of the bounds. The
      criteria are the ability to maintain the stated test size and the simulated power
      of the tests using these bounds. Bounds that perform well for small sample size
      are preferred. We present a computational example to demonstrate the methods
      described in the article.

PMID- 16279352
TI  - The fallback procedure for evaluating a single family of hypotheses.
AB  - In testing multiple hypotheses, control of the familywise error rate is often
      considered. We develop a procedure called the "fallback procedure" to control the
      familywise error rate when multiple primary hypotheses are tested. With the
      fallback procedure, the Type I error rate (alpha) is partitioned among the
      various hypotheses of interest. Unlike the standard Bonferroni adjustment,
      however, testing hypotheses proceeds in an order determined a priori. As long as
      hypotheses are rejected, the Type I error rate can be accumulated, making tests
      of later hypotheses more powerful than under the Bonferroni procedure. Unlike the
      fixed sequence test, the fallback test allows consideration of all hypotheses
      even if one or more hypotheses are not rejected early in the process, thereby
      avoiding a common concern about the fixed sequence procedure. We develop
      properties of the fallback procedure, including control of the familywise error
      rate for an arbitrary number of hypotheses via illustrating the procedure as a
      closed testing procedure, as well as making the test more powerful via alpha
      exhaustion. We compare it to other procedures for controlling familywise error
      rates, finding that the fallback procedure is a viable alternative to the fixed
      sequence procedure when there is some doubt about the power for the first
      hypothesis. These results expand on the previously developed properties of the
      fallback procedure (Wiens, 2003). Several examples are discussed to illustrate
      the relative advantages of the fallback procedure.

PMID- 16279353
TI  - Decision-theoretic views on simultaneous testing of superiority and
      noninferiority.
AB  - In a simultaneous testing of noninferiority and superiority in clinical trials,
      there is no multiplicity penalty. Ng (2003), however, argues that even though
      there is no inflation of the Type I error rate, this type of simultaneous testing
      is problematic because it may lead to loss of power in the subsequent
      confirmatory trial. And he recommends to conduct only one test chosen on the
      basis of the sponsor's preliminary assessment. We view the question of whether
      one should simultaneously test for noninferiority and superiority from a decision
      theoretic view point. We develop the loss function approach implicit in Ng's
      research and compare his recommendation to simultaneous testing procedures
      indexed by a variety of design parameters. We find that the simultaneous testing
      procedure generally provides smaller loss than Ng's method, except when the prior
      distribution allocates a large probability to equivalence of the two treatments.

PMID- 16279354
TI  - Sample size calculation for simulation-based multiple-testing procedures.
AB  - In this article, we present a simple method to calculate sample size and power
      for a simulation-based multiple testing procedure which gives a sharper critical
      value than the standard Bonferroni method. The method is especially useful when
      several highly correlated test statistics are involved in a multiple-testing
      procedure. The formula for sample size calculation will be useful in designing
      clinical trials with multiple endpoints or correlated outcomes. We illustrate our
      method with a quality-of-life study for patients with early stage prostate
      cancer. Our method can also be used for comparing multiple independent groups.

PMID- 16279355
TI  - Sample size computation for two-sample noninferiority log-rank test.
AB  - When an experimental therapy is less extensive, less toxic, or less expensive
      than a standard therapy, we may want to prove that the former is not worse than
      the latter through a noninferiority trial. In this article, we discuss a
      modification of the log-rank test for noninferiority trials with survival
      endpoint and propose a sample size formula that can be used in designing such
      trials. Performance of our sample size formula is investigated through
      simulations. Our formula is applied to design a real clinical trial.

PMID- 16279356
TI  - Maximum likelihood estimation in survival studies under progressive interval
      censoring with random removals.
AB  - Censoring occurs commonly in clinical trials. This article investigates a new
      censoring scheme, namely, Type II progressive interval censoring with random
      removals to cope with the setting that patients are examined at fixed regular
      intervals and dropouts may occur during the study period. We discuss the maximum
      likelihood estimation of the model parameters and derive the corresponding
      asymptotic variances when survival times are assumed to be Weibull distributed.
      An example is discussed to illustrate the application of the results under this
      censoring scheme.

PMID- 16279357
TI  - Analysis of longitudinal binary data with missing data due to dropouts.
AB  - Longitudinal binary data from clinical trials with missing observations are
      frequently analyzed by using the Last Observation Carry Forward (LOCF) method for
      imputing missing values at a visit (e.g., the prospectively defined primary visit
      time point for analysis at the end of treatment period). Usually, to understand
      time trend in treatment response, analyses are also performed separately on data
      at intermediate time points. The objective of such analyses is to estimate the
      proportion of "response" at a time point and then to compare two treatment groups
      (e.g., drug vs. placebo) by testing for the difference in the two proportions of
      response. The commonly used methods are Fisher's exact test, chi-squared test,
      Cochran-Mantel-Haenszel test, and logistic regression. Analyses based on the
      Observed Cases (OC) data are usually also performed and compared with those
      obtained by LOCF. Another approach that is gaining popularity (after the
      introduction of PROC GENMOD by the SAS Institute) is to use the method of
      Generalized Estimating Equations (GEE) with a view to include all repeated
      observations in the analysis in a more comprehensive manner. It is now well
      recognized, however, that results obtained by these methods are susceptible to
      bias, depending on the "missing data mechanism." Of particular concern is the
      bias introduced by NMAR dropouts. Because there is no one method to
      satisfactorily handle dropouts in data analysis, consensus is gathering toward
      doing analyses by several methods (including methods to handle NMAR dropouts) to
      evaluate sensitivity of results to model assumptions. In this article, we
      demonstrate application of the following methods for handling dropouts in
      longitudinal binary data: Generalized Linear Mixture Models (GLMM) (for handling
      NMAR dropouts), Weighted GEE (for handling MAR dropouts), and GEE (MCAR
      dropouts). The results are also compared with those obtained by logistic
      regression (univariate) on both LOCF and OC data.

PMID- 16279358
TI  - Hypoglycemia, hypoglycemia unawareness and counterregulation in children and
      adolescents with type 1 diabetes mellitus.
AB  - Three clinical phenomena have been defined in the last decade in patients with
      diabetes mellitus as a dangerous iatrogenic sequel of hypoglycemia. These are
      hypoglycemia unawareness, defective glucose counterregulation and a lowered
      hypoglycemic threshold for hypoglycemic symptoms. Former mild hypoglycemia
      episodes cause a decrease and a delay in the protective hormonal
      counterregulatory response and warning symptoms in subsequent episodes, and in
      the absence of these, risk of severe hypoglycemia increases considerably. It has
      been demonstrated that when protection is provided against hypoglycemia with
      strict monitoring programs designed to avoid even mild hypoglycemia episodes,
      blunted autonomic symptoms and counterregulatory hormonal responses are
      rectified. Therefore, the best course of action in the treatment of pediatric
      diabetes mellitus is frequent blood sugar measurements, flexible multiple dose
      insulin regimens facilitating insulin dose adjustments as required, and a diet.
      In order to implement this, it is essential to organize an intensive training
      program with the patient and family, and to provide psychological support and
      close coordination with the diabetes treatment team.

PMID- 16279359
TI  - Girls with gonadotrophin-dependent precocious puberty: do they all deserve
      neuroimaging?

PMID- 16279360
TI  - Central precocious puberty in girls: prediction of the aetiology.

PMID- 16279361
TI  - The gonadotrophins response to GnRH test is not a predictor of neurological
      lesion in girls with central precocious puberty.
AB  - OBJECTIVES: To assess the value of gonadotrophin releasing hormone (GnRH)
      stimulation test in identifying intracranial abnormality in girls with central
      precocious puberty (CPP). PATIENTS AND METHODS: A study of 67 girls diagnosed
      with CPP who underwent cranial MRI scans. Patients were not receiving any therapy
      and there were no neurological signs or symptoms at presentation. Patients
      underwent evaluation of GnRH stimulation test and plasma oestradiol levels at
      presentation. RESULTS: Mean age at onset of puberty was 6.2 years (range 2.0 to
      8.0 years). Intracranial abnormalities were present in 10 (15%) patients, while
      57 girls (85%) had no abnormalities. No significant difference was shown between
      girls with intracranial abnormality and girls without intracranial abnormality in
      basal LH or FSH values, peak LH or FSH values, LH/FSH peak ratios, peak LH/basal
      LH ratios, peak FSH/ basal FSH ratios at presentation. CONCLUSION: GnRH
      stimulation test does not identify those with underlying intracranial abnormality
      at presentation. MRI imaging remains necessary in all cases of central precocious
      puberty in girls.

PMID- 16279362
TI  - Hypopituitarism and neurodevelopmental abnormalities in relation to central
      nervous system structural defects in children with optic nerve hypoplasia.
AB  - OBJECTIVE: Optic nerve hypoplasia (ONH) is a heterogeneous disease with variable
      findings of pituitary insufficiency, CNS and neurodevelopmental abnormalities. We
      characterized the spectrum of endocrinopathy in a cohort of children with ONH and
      attempted to correlate the presence of different midline CNS findings with the
      degree of hypopituitarism. The correlation of variable CNS abnormalities with the
      presence of a seizure disorder and neurodevelopmental delay was also examined.
      METHODS: Charts of 56 patients with ONH referred to our endocrine clinics between
      1990 and 2000 were reviewed. Neurodevelopmental assessment was based on
      questionnaires sent to families during the study period. RESULTS: Forty-six
      patients (82%) had hypopituitarism, with growth hormone deficiency being the most
      common endocrinopathy. All patients with diabetes insipidus, hypocortisolism, and
      hypogonadotropin hypogonadism also had combined pituitary hormone deficiency.
      Evolving pituitary hormone deficiency was observed in two of 37 patients
      diagnosed with hypopituitarism in the first 3 years of life. No single midline
      CNS finding correlated with the presence of hypopituitarism or a seizure
      disorder. However, hydrocephalus or a seizure disorder was more commonly seen in
      patients with developmental delay. CONCLUSION: ONH is a heterogeneous disorder
      with possible multifactorial etiologies. All patients with this diagnosis deserve
      a comprehensive endocrine and neurodevelopmental evaluation.

PMID- 16279363
TI  - MC4R marker associated with stature in children and young adults: a longitudinal
      study.
AB  - We investigated the associations between a polymorphism in the melanocortin 4
      receptor (MC4R) gene and changes in body size and composition from childhood to
      adulthood in the Quebec Family Study. Ninety-one subjects (43 males) less than 18
      years of age (mean age 13.5 +/- 2.4 years; range 8.4-17.8 years) at baseline were
      re-measured 11.2 years later on average. The anthropometric variables analyzed
      were height, weight, body mass index, percent body fat, sum of skinfolds, fat
      mass index, and fat free mass index (FFMI). All variables were adjusted for age
      and sex. The subjects were genotyped for the MC4R C-2745T polymorphism. Forty
      five subjects were homozygotes for the common allele (C/C), 36 were heterozygotes
      (C/T) and 10 were homozygotes for the rare allele (T/T). The rare allele was
      associated with increased height at baseline as well as at the follow-up visit.
      Although FFMI tended to increase more in subjects carrying the rare allele, no
      significant differences were found for the changes over time for the other
      phenotypes. These results suggest that DNA sequence variation in the MC4R locus
      may contribute to the gain in body height from childhood to adulthood.

PMID- 16279364
TI  - Prevalence and characteristics of type 2 diabetes mellitus in 9-18 year-old
      children with diabetic ketoacidosis.
AB  - OBJECTIVE: To estimate the prevalence of type 2 diabetes mellitus (DM2) in 9-18
      year-old children with diabetic ketoacidosis (DKA) and to describe the presenting
      biochemical characteristics and response to standardized DKA treatment. METHODS:
      Data were collected from a consecutive sample of 9-18 year-old children
      presenting with DKA. DKA was defined as hyperglycemia and ketosis with an initial
      pH <7.3, or bicarbonate <15 mmol/l. Patients were classified as having DM2 if
      they had negative autoantibody status and normal or elevated fasting C-peptide.
      RESULTS: The prevalence of DM2 in patients with DKA was 13.0% (6.1-23.3%). There
      was no significant difference in the presenting pH (7.14 vs 7.15), but blood
      glucose was higher (735 vs 587 mg/dl) in patients with DM2, than in patients with
      type 1 DM (DM1). The duration of insulin infusion until resolution of acidosis
      (17.3 vs 13.2 h) and intensive care unit stay (2.4 vs 1.6 days) were longer in
      patients with DM2. Seven of the nine patients with DM2 did not require insulin at
      1-year follow-up. CONCLUSIONS: Children with DM2 can present with DKA and
      constitute a significant percentage in the above 9-year age group. The need for
      insulin must be carefully re-evaluated as DKA resolves in these patients.
      Adolescents with DM2 and their families need to be educated about DKA.

PMID- 16279365
TI  - Decreased first phase insulin response in children with congenital insensitivity
      to pain with anhidrosis.
AB  - Nerve growth factor (NGF) and its receptor tyrosine kinase A (TrkA) participate
      in endocrine pancreas morphogenesis and insulin secretion in vitro. Mutations in
      the TrkA gene cause the syndrome of congenital insensitivity to pain with
      anhydrosis (CIPA). We hypothesized that CIPA may represent a natural model for
      impaired NGF effect on insulin secretion in humans. Glucose challenge tests were
      performed in seven children with CIPA. We calculated the first phase insulin
      response (FPIR), the second phase insulin response (SPIR) and glucose disposal
      rate. FPIR was impaired in four and borderline in two patients. SPIR and glucose
      disposal rate were within the normal range. Oral glucose tolerance test was
      normal in all patients. Low FPIR in. CIPA suggests for the first time that the
      NGF-TrkA pathway may play a role in insulin secretion in response to glucose
      challenge in humans. Additional studies on the clinical significance of NGF-TrkA
      effects on insulin secretion are required.

PMID- 16279366
TI  - Early changes in 24-hour ambulatory blood pressure are associated with high
      normal albumin excretion rate in children with type 1 diabetes mellitus.
AB  - OBJECTIVE: The relationship between urinary albumin excretion rate (AER) and
      elevated blood pressure (BP) is unclear as a cause-effect phenomenon in the
      development of diabetic nephropathy. The aim of this study was to examine the
      association between AER, HbA1c and BP in children with normoalbuminuria. METHODS:
      24-hour ambulatory BP assessment was performed in 78 children with type 1
      diabetes mellitus (DM1), age mean +/- SD 13.4 +/- 2.7 yr, range 7.3-18.3 yr, DM1
      duration mean +/- SD 6.6 +/- 2.9 yr, range 2.1-11.9 yr. Using generalised linear
      mixed models with systolic (SBP) and diastolic (DBP) blood pressure as dependent
      variables, the effects of AER and HbA1c were examined, adjusting for age, gender,
      DM1 duration and insulin dose. RESULTS: Patients with high normal AER (7-20
      microg/min) had higher SBP during daytime and night-time compared to the low
      normal AER (< or = 7 microg/min) (mean +/- SD 118.20 +/- 7.98 and 110.33 +/- 7.08
      mm Hg, p = 0.02; mean +/- SD 108.76 +/- 9.21 and 100.20 +/- 7.75 mm Hg, p = 0.03,
      respectively). DBP was also higher both during day- and night-time when compared
      to the < or = 7 microg/min group (mean +/- SD 73.40 +/- 6.50 and 64.86 +/- 5.67
      mm Hg, p = 0.002; mean +/- SD 62.50 +/- 6.75 and 56.30 +/- 5.56 mm Hg, p = 0.03
      day- and night-time, respectively). CONCLUSION: A rise in SBP and DBP is
      associated with increased levels of AER even within the normal range.

PMID- 16279367
TI  - Pregnancy outcomes in women with classical congenital adrenal hyperplasia due to
      21-hydroxylase deficiency.
AB  - OBJECTIVE: Despite earlier detection, treatment, and surgical advances, fertility
      prognosis in women with classical 21-hydroxylase deficiency (21-OHD) is still
      low, especially in the salt-wasting (SW) form. PATIENTS AND METHODS: We analysed
      the course and outcome of four pregnancies in two simple virilizing (SV) and one
      SW patient. RESULTS: The evaluation of carrier status indicated that all three
      fathers had two normal CYP21 genes. During the pregnancy, the dose of
      prednisolone was increased in one of the SV patients and the SW patient. In the
      SW patient who developed pre-eclampsia, the dose of fludrocortisone was also
      increased. Three patients gave birth to a total of four healthy girls who were
      heterozygotes for 21-OHD with normal genitalia (one by vaginal delivery and three
      by Caesarean section). Family studies revealed that the mother of the SW patient
      has nonclassical 21-OHD. CONCLUSION: Improving a low birth rate in females with
      SW 21-OHD remains a problem and new approaches are required. If the mother has 21
      OHD (even nonclassical 21-OHD), pre-conception counselling and paternal
      genotyping are advisable and prenatal dexamethasone therapy should be considered.

PMID- 16279368
TI  - Near normalisation of lumbar spine bone density in young women with osteopenia
      recovered from adolescent onset anorexia nervosa: a longitudinal study.
AB  - To investigate the effect of the progression of adolescent onset anorexia nervosa
      (AN) on bone parameters we followed two cohorts (Disease cohort and recovered
      cohort) of adolescents for a total of 5.2 years. In the 'Disease' cohort (n =
      18), lumbar spine bone density (BMD) was reduced by 0.6 SD after 0.8 years of
      disease and was reduced a further 1.0 SD after a total 2.5 years of disease (p <
      0.001). At the third lumbar vertebra there was bone loss (-3.7%, p < 0.05)
      resulting in reduced volumetric BMD (-5.1%, p < 0.08). In the 'recovered' cohort,
      lumbar spine BMD was reduced by 1.9 SD after 1.7 years of disease, and increased
      by 1.5 SD after 2.7 years of recovery (p < 0.001). At the third lumbar vertebra
      there was an increase in bone mass (20.5%, p < 0.001) and bone volume (14.1%, p <
      0.001), resulting in increased volumetric BMD (6.3%, p < 0.08). Normalisation of
      lumbar spine BMD may be achieved in patients with adolescent onset AN when the
      successful recovery of body weight is combined with the return of regular menses.

PMID- 16279369
TI  - Constitutional delayed puberty in males and hypogonadotropic hypogonadism: a
      reliable and cost-effective approach to differential diagnosis.
AB  - Forty-six male teenagers 13-19 years old with delayed puberty (DP) underwent
      gonadotropin releasing hormone (GnRH) and human chorionic gonadotropin (HCG)
      stimulation as part of their work-up. All were followed to age 18 and beyond.
      Thirty-seven had constitutional delayed puberty (CDP). Nine had hypogonadotropic
      hypogonadism (HH). At referral 34 youngsters with CDP were properly diagnosed
      when the lower limit for the luteinizing hormone (LH) response to GnRH (Factrel
      0.1 mg i.v.) was set at 12 IU/l. Three boys with CDP failed to reach that level
      and were not assigned appropriately. All nine patients with HH had basal serum
      testosterone (T) < 50 ng/dl when first seen and LH responses to GnRH stimulation
      < 8.0 IU/l. In the late 1970s, five subjects with DP were given HCG 3,000 IU (two
      patients daily for 5 days; three on 3 alternate days). Serum T was measured
      before the first, and 48 hours after the last injection (day 7). With recognition
      of the long biological half-life of injected HCG and receptor downregulation by
      daily doses, the protocol was changed. In the early 1980s, the dose of HCG was
      randomized to either 500 IU or 1,000 IU given on 3 alternate days. T was measured
      before the first injection (basal), 48 hours later (day 3) and 48 hours after the
      third injection (day 7). At referral 35 patients with CDP, including one GnRH
      failure, met the criterion for a positive response to HCG stimulation based on
      their own reactions (T > 170 ng/dl on day 3; > 200 on day 7). Eleven patients
      with DP failed the test. Nine had HH and two had CDP. The nine patients with HH
      included the two given daily injections and the three given HCG 3,000 IU on 3
      alternate days. Of the two with CDP, one, an obese boy with a normal GnRH test,
      only received 500 IU HCG (5.6 IU/kg), which may have been inadequate. The other
      failed both tests. Of the 35 responders, 17 (group 1) were given HCG 500 IU and
      18 (group 2) were given 1,000 IU i.m. on 3 alternate days. Seven boys in group 1
      and 12 in group 2 had serum T determined on day 3, and all 35 had T measured on
      day 7. There was no significant difference between the basal T levels in the two
      groups or in their responses to HCG, and the results were pooled. The combined
      data in the patients with CDP were then compared with those of the nine patients
      with HH, recognizing that the result on day 7 in the two patients given daily
      injections may reflect receptor down-regulation. Setting the limit for a normal T
      response at > 170 ng/dl 48 hours after a single injection of HCG and > 200 ng/dl
      after the third injection assigned all the patients with CDP appropriately. The
      data on the patients with HH are less complete, with only three T values 48 hours
      after the first injection However, even after three injections of HCG on
      alternate days, only one of nine patients with HH approached the lowest level
      achieved by the patients with CDP after a single injection. The data confirm that
      a basal serum T 50 ng/dl is evidence of the onset of puberty. In those with serum
      T < 50 ng/ dl our data suggest that a single injection of HCG 15 IU/kg, with
      serum T determined 48 hours later, is more discriminatory and offers the most
      reliable, easy to perform, least painful, and by far the most cost effective test
      to differentiate CDP from HH.

PMID- 16279370
TI  - Hypogonadotropic hypogonadism associated with cleidocranial dysostosis.
AB  - BACKGROUND: Cleidocranial dysostosis (CCD) is a rare autosomal dominant disease
      with high penetrance and extremely variable expression. Some of the clinical
      manifestations include large, broad and short cranium with frontal and parietal
      bossing and a supraglabellar depression, facial part of the cranium relatively
      small with hypertelorism, absent or poorly defined superior and inferior
      clavicular depressions. PATIENT REPORT: A 17 year-old girl with CCD was referred
      to the pediatric endocrinology and metabolism clinic because she failed to reach
      any signs of puberty.

PMID- 16279371
TI  - Reversible weight gain and prolactin levels--long-term follow-up in childhood.
AB  - In adult patients weight gain is a frequent complaint of hyperprolactinaemia and
      it has been associated with a high prevalence of obesity. Normalization of
      prolactin (PRL) levels result in weight loss. The nature of this link is poorly
      defined. In this report we describe a 14 year-old female with primary amenorrhea
      and persistent progressive weight gain. The patient's height, weight and BMI were
      152 cm, 70 kg, and 30.3 kg/m2, respectively. Basal hormonal investigation showed
      normal free thyroxin, TSH, IGF-I, cortisol and ACTH values. Serum PRL level was
      very high (16,278 mIU/l; normal range 63-426 mIU/l). Magnetic resonance imaging
      scan showed the presence of a pituitary microadenoma. Treatment with the non
      selective dopamine agonist pergolide caused a significant reduction of serum PRL
      concentration with a remarkable decrease of body weight. During follow-up, repeat
      MRI scan revealed disappearance of the microadenoma. The reduction of the daily
      dose of pergolide was associated with an increase of serum PRL with significant
      weight gain. A further reduction of body weight was subsequently observed with an
      increase of pergolide dosage. Serum PRL measurement may be useful as part of the
      endocrine work-up of obese children with a history of unexplained recent weight
      gain, especially if associated with pituitary-gonadal axis dysfunction. The
      relationship between PRL secretion and weight change needs to be examined in
      prospective larger studies.

PMID- 16279372
TI  - Coincidence of multiple endocrine neoplasia type IIa and type 1 diabetes
      mellitus.

PMID- 16279373
TI  - Canine influenza virus surfaces.

PMID- 16279374
TI  - Loss of livestock reaches millions.

PMID- 16279375
TI  - Companies contribute to animal rescue and relief.

PMID- 16279376
TI  - Humans receive skilled care at veterinary school hospital.

PMID- 16279377
TI  - Hurricanes double up on Kornegay.

PMID- 16279378
TI  - Disagrees with AVMA stand on foie gras production.

PMID- 16279379
TI  - More on law/animal rights.

PMID- 16279380
TI  - Additional comments on revised sow housing policy.

PMID- 16279381
TI  - Additional comments on revised sow housing policy.

PMID- 16279382
TI  - Abandoned dog becomes unexpected gift.

PMID- 16279383
TI  - What is your diagnosis? Pneumatosis coli.

PMID- 16279384
TI  - Strategies for the diagnosis and treatment of ovarian cysts in dairy cattle.

PMID- 16279386
TI  - Cardiopulmonary effects of controlled versus spontaneous ventilation in pigeons
      anesthetized for coelioscopy.
AB  - OBJECTIVE: To evaluate the cardiorespiratory effects of controlled versus
      spontaneous ventilation in pigeons anesthetized for coelioscopy. DESIGN:
      Prospective study. ANIMALS: 30 healthy adult pigeons (Columbia livia). PROCEDURE:
      During isoflurane anesthesia, 15 pigeons were allowed to breathe spontaneously
      (SP group) and 15 were mechanically ventilated (MV group) by use of a pressure
      limited ventilator. In each group, cardiopulmonary variables (including end-tidal
      CO2 concentration [ETCO2]) were measured before (baseline), during, and after
      coelioscopy. An arterial blood sample was collected for blood gas analyses from
      each pigeon before coelioscopy and after the procedure, when the caudal thoracic
      air sac was still open. RESULTS: At baseline, hypoventilation was greater in the
      SP group than the MV group. Compared with the SP group values, ETCO2
      overestimated PaCO2 to a greater degree in the MV group. Cardiovascular variables
      were not different between groups. After coelioscopy (when the air sac was open),
      PaCO2 had decreased significantly from baseline in the MV group. In the SP group,
      hypoventilation worsened despite an increase in respiratory rate. After
      coelioscopy, PaO2 in the SP group had decreased from baseline and was lower than
      PaO2 in the MV group; arterial blood pressure and heart rate in the MV group had
      decreased from baseline and were lower than values in the SP group. CONCLUSIONS
      AND CLINICAL RELEVANCE: In adult pigeons, controlled ventilation delivered by a
      pressure-limited device was not associated with clinically important adverse
      cardiopulmonary changes but may be associated with respiratory alkalosis and
      cardiovascular depression when air sac integrity has been disrupted.

PMID- 16279385
TI  - Evaluation of hemodynamic measurements, including lithium dilution cardiac
      output, in anesthetized dogs undergoing ovariohysterectomy.
AB  - OBJECTIVE: To measure cardiac output in healthy female anesthetized dogs by use
      of lithium dilution cardiac output and determine whether changes in mean arterial
      pressure were caused by changes in cardiac output or systemic vascular
      resistance. DESIGN: Prospective clinical study. ANIMALS: 20 healthy female dogs.
      PROCEDURE: Dogs were anesthetized for ovariohysterectomy. Ten dogs breathed
      spontaneously throughout anesthesia, and 10 dogs received intermittent positive
      pressure ventilation. Cardiovascular and respiratory measurements, including
      lithium dilution cardiac output, were performed during anesthesia and surgery.
      RESULTS: Mean arterial pressure and systemic vascular resistance index were low
      after induction of anesthesia and just prior to surgery and increased
      significantly after surgery began. Cardiac index (cardiac output indexed to body
      surface area) did not change significantly throughout anesthesia and surgery.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results provide baseline data for cardiac
      output and cardiac index measurements during clinical anesthesia and surgery in
      dogs. Changes in mean arterial pressure do not necessarily reflect corresponding
      changes in cardiac index.

PMID- 16279387
TI  - Supraspinatus tendinosis associated with biceps brachii tendon displacement in a
      dog.
AB  - A 4-year-old spayed female Australian Cattle Dog (Blue Heeler) was evaluated
      because of right forelimb lameness of 5 months' duration. Orthopedic evaluation
      revealed signs of pain localized to the cranial aspects of both shoulder joints.
      Via magnetic resonance imaging, the mass of the supraspinatus tendon insertion in
      both shoulder joints was increased, compared with findings in cadavers of
      clinically normal dogs; additional imaging procedures revealed that, compared
      with clinically normal tendons, the tendon had increased signal intensity that
      was consistent with increased fluid content. The increased supraspinatus tendon
      mass in each shoulder joint was associated with medial displacement of the biceps
      brachii tendon, which was more severe in the right limb. Arthroscopic evaluations
      of both shoulder joints revealed no abnormalities. The dog underwent surgery, and
      the abnormal parts of the tendons were resected. The most prominent finding on
      histologic examination of excised tissues was severe myxomatous degeneration. The
      lameness resolved, and at 22 months after surgery, the dog was reported to have
      had no recurrence of lameness. The clinical signs and histologic appearance of
      the tendons in this dog strongly resemble findings associated with tendinosis in
      humans. Decompression of the biceps brachii tendon may have contributed to the
      successful outcome after surgery in this dog. Supraspinatus tendinosis should be
      considered among the differential diagnoses in dogs with uni- or bilateral
      forelimb lameness.

PMID- 16279388
TI  - Putative aqueous humor misdirection syndrome as a cause of glaucoma in cats: 32
      cases (1997-2003).
AB  - OBJECTIVE: To characterize the clinical and morphologic aspects of aqueous humor
      misdirection syndrome (AHMS) in cats and provide a hypothesis regarding its
      pathogenesis on the basis of detailed analysis of affected cats. DESIGN:
      Retrospective study. ANIMALS: 32 cats (40 eyes). PROCEDURE: Medical records of
      cats in which AHMS was diagnosed from July 1997 to August 2003 were reviewed. In
      certain cats, results of additional diagnostic testing were also obtained,
      including A-scan, B-scan, and high-resolution ultrasonography; streak
      retinoscopy; video keratometry; and infrared neutralizing videoretinoscopy as
      well as results of analysis of flash-frozen sections and histologic examination
      of enucleated globes. RESULTS: Cats had a uniformly shallow anterior chamber,
      intact lens zonules, and a narrowed approach to an open iridocorneal angle. Mean
      age of affected cats was 11.7 years (range, 4 to 16 years), and female cats were
      significantly more often affected than male cats. Clinical signs included
      mydriasis, decreased pupillary light reflex, decreased menace response, and
      blindness. Glaucomatous changes to the optic nerve, incipient cataracts, and
      eventual blindness were seen. Intraocular pressure was > or = 20 mm Hg (range, 12
      to 58 mm Hg) in 32 of 40 eyes. Ultrasonography and histologic examination
      revealed a thickened anterior vitreal face interposed between the lens and
      ciliary body, partial ciliary cleft collapse, and cavitated vitreal regions.
      Various treatment modalities were used. CONCLUSIONS AND CLINICAL RELEVANCE: AHMS
      affects older cats, especially females, and may result in glaucoma, vision loss,
      and signs of ocular pain. Topical administration of carbonic anhydrase inhibitors
      decreased intraocular pressure.

PMID- 16279389
TI  - Outcome of dogs with high-grade soft tissue sarcomas treated with and without
      adjuvant doxorubicin chemotherapy: 39 cases (1996-2004).
AB  - OBJECTIVE: To examine the effect of adjuvant doxorubicin chemotherapy on outcome
      in dogs with high-grade (grade 3) soft tissue sarcomas (HGSTSs). DESIGN:
      Retrospective case series. ANIMALS: 39 dogs. PROCEDURES: Medical records of dogs
      with HGSTSs were reviewed. Dogs treated with surgery alone or receiving single
      agent doxorubicin chemotherapy postoperatively were included in the study. Owners
      and referring veterinarians were contacted for follow-up information. Slides from
      histologic sections were reviewed to confirm the diagnosis of HGSTSs. Cases in
      which follow-up examination was not performed and radiation therapy or
      chemotherapy other than doxorubicin was administered were excluded. RESULTS: 39
      dogs met inclusion criteria. Twenty-one dogs received adjuvant doxorubicin. Tumor
      , patient-, and treatment-related variables were not significantly associated
      with measured outcomes including local, metastatic, and overall disease-free
      intervals as well as survival time. Overall median disease-free interval was 724
      days with a median survival time of 856 days for all dogs. CONCLUSIONS AND
      CLINICAL RELEVANCE: Adjuvant doxorubicin-based chemotherapy did not benefit this
      population of dogs with HGSTSs. Outcome for visceral HGSTSs was similar to that
      of nonvisceral HGSTSs in these cases.

PMID- 16279390
TI  - Cardiac lymphoma and pericardial effusion in dogs: 12 cases (1994-2004).
AB  - OBJECTIVE: To determine clinical characteristics and clinicopathologic findings,
      including results of pericardial fluid analysis, and determine the outcome
      associated with pericardial effusion caused by cardiac lymphoma in dogs. DESIGN:
      Retrospective case series. ANIMALS: 12 dogs. PROCEDURE: Medical records of
      affected dogs were reviewed for echocardiographic findings, radiographic
      findings, results of pericardial fluid analysis, clinicopathologic findings,
      treatment protocols, and outcomes. RESULTS: Pericardial effusion was detected by
      echocardiography in all 12 dogs, and lymphoma was detected by cytologic
      examination of the effusion (11/12 dogs) or histologic examination of pericardium
      (3/12). Large-breed dogs were overrepresented; median weight was 40.5 kg (89.1
      lb). Most hematologic and biochemical changes were mild and non-specific.
      Survival time for dogs treated with combination chemotherapeutic agents was 157
      days and for dogs that did not receive chemotherapy survival time was 22 days.
      This difference was not significant, but several dogs had long-term survival.
      CONCLUSIONS AND CLINICAL RELEVANCE: Cardiac lymphoma is an uncommon cause of
      pericardial effusion, and results suggest that cardiac lymphoma does not always
      warrant the poor prognosis of other stage V, substage b lymphomas.

PMID- 16279391
TI  - Prognostic value of magnetic resonance imaging in dogs with paraplegia caused by
      thoracolumbar intervertebral disk extrusion: 77 cases (2000-2003).
AB  - OBJECTIVE: To determine whether magnetic resonance imaging findings in dogs with
      paraplegia caused by thoracolumbar intervertebral disk extrusion were predictive
      of clinical outcome. DESIGN: Retrospective case series. ANIMALS: 77 dogs.
      PROCEDURE: Medical records and magnetic resonance images were reviewed; clinical
      outcome was classified as successful (regained ability to walk with no more than
      mild neurologic deficits) or unsuccessful (severe neurologic deficits persisted).
      The prognostic value of magnetic resonance imaging was compared with prognostic
      value of deep pain perception, duration of clinical signs, and rate of onset of
      clinical signs. RESULT: 33 (43%) dogs had areas of hyperintensity of the spinal
      cord greater than or equal to the length of the L2 vertebral body on T2-weighted
      magnetic resonance images. All 44 dogs without areas of hyperintensity on T2
      weighted images had a successful outcome, but only 18 of the 33 (55%) dogs with
      an area of hyperintensity did. Only 5 of 16 dogs with an area of hyperintensity
      that had also lost deep pain perception had a successful outcome. The odds ratio
      for an unsuccessful outcome for a dog with an area of hyperintensity (29.87) was
      higher than the odds ratio for a dog that had lost deep pain perception (5.24).
      Duration and rate of onset of clinical signs were not associated with clinical
      outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggest that results of
      magnetic resonance imaging can be used to predict clinical outcome in dogs with
      paraplegia caused by intervertebral disk extrusion.

PMID- 16279392
TI  - Relationship between antimicrobial susceptibility of clinical mastitis pathogens
      and treatment outcome in cows.
AB  - OBJECTIVE: To determine whether there was any association between results of in
      vitro antimicrobial susceptibility testing of pathogens isolated from cows with
      mild or moderate clinical mastitis and outcome of treatment. DESIGN:
      Observational study. ANIMALS: 133 cows with mild or moderate mastitis in a single
      quarter. PROCEDURE: Cows were treated by means of intramammary infusion of
      pirlimycin (50 mg) in the affected quarter once daily for 2 days; additional
      intramammary treatments with the same product were administered if the milk
      continued to appear abnormal. Duration of treatment and days until clinical cure
      were recorded. Bacterial isolates were tested for antimicrobial susceptibility by
      means of a broth micro-dilution technique. RESULTS: Environmental streptococci,
      coliforms, and coagulase-negative Staphylococcus spp were the most commonly
      isolated pathogens. Duration of treatment and days until clinical cure were not
      significantly different for cows from which pathogens that were susceptible or
      resistant to pirlimycin were isolated. Bacteriologic cure rates 14 and 21 days
      after treatment were not significantly different for cows with mastitis caused by
      susceptible or resistant bacteria. Similar results were found when data only from
      cows with mastitis caused by gram-positive isolates were analyzed. CONCLUSIONS
      AND CLINICAL RELEVANCE: In the present study, differences in clinical outcome for
      cows with mild or moderate mastitis that could be attributed to differences in
      results of in vitro susceptibility testing were not identified. The use of in
      vitro susceptibility testing to guide intramammary mastitis treatment cannot be
      recommended on the basis of results of this study.

PMID- 16279393
TI  - Ultrasonographic assessment of change in abomasal position during the last three
      months of gestation and first three months of lactation in Holstein-Friesian
      cows.
AB  - OBJECTIVE: To determine changes in abomasal position and dimensions during the
      last 3 months of gestation and first 3 months of lactation via transabdominal
      ultrasonography and determine whether surgical correction of left-displaced
      abomasum (LDA) by right flank omentopexy alters abomasal position within the
      abdomen in Holstein-Friesian cows. DESIGN: Observational study. ANIMALS: 20
      heifers and 20 cows with no history of an LDA and 7 cows that had been treated
      for LDA via right flank omentopexy during an earlier lactation. Procedure
      Ultrasonographic measurements were obtained 8 times during the last 3 months of
      gestation and first 3 months of lactation. Abomasal length, width, and volume
      were calculated from these measurements. RESULTS: The abomasum was always wider
      than it was long and located predominantly to the right of the midline. The
      presence of a right flank omentopexy had no effect on the measured parameters.
      Abomasal length decreased and width increased during the last 3 months of
      gestation, resulting in a more transverse orientation of the abomasum within the
      abdomen. These changes appeared to be in response to cranial expansion of the
      gravid uterus. The abomasum returned to a more caudal and right sagittal position
      within 14 days after parturition. CONCLUSIONS AND CLINICAL RELEVANCE: Abomasal
      dimensions, position, and volume change markedly during the last 3 months of
      gestation and first 3 months of lactation. Results permit detection of abnormal
      abomasal position in ill cows and indicate that the preferred location for
      abomasopexy is 20 cm caudal to the xiphoid process and 5 to 10 cm to the right of
      the ventral mid-line.

PMID- 16279394
TI  - Protothecal enteritis as a cause of protein-losing enteropathy in a bull.
AB  - Prototheca spp are achlorophyllic saprophytic algae found in wastewater, sewage,
      agricultural waste, and possibly elsewhere in the environment. Infections with
      these organisms have been reported in cattle, humans, and dogs; affected cattle
      commonly develop mastitis. A 5-year-old Brahman-cross bull was evaluated because
      of a history of diarrhea and weight loss. The history and physical examination
      and clinicopathologic findings were similar to those associated with
      granulomatous enteritis caused by Mycobacterium avium subsp paratuberculosis
      (Johne's disease), which is the most common protein-losing enteropathy of cattle.
      However, diagnostic tests for paratuberculosis yielded negative results. Biopsy
      specimens from the ileum, jejunum, and ileocecal lymph node were collected for
      histologic examination and preparation of tissue impression smears; Prototheca
      like organisms were identified. Because of the poor prognosis associated with
      this infection and the lack of safe and economical therapeutic agents for cattle,
      the owner decided to euthanatize the bull. Infection with Prototheca organisms
      was confirmed postmortem. As this case illustrates, protothecosis may be a cause
      of granulomatous enteritis in cattle.

PMID- 16279395
TI  - Gastrointestinal problems as a cause of iron deficient anaemia.

PMID- 16279396
TI  - Large hiatal hernia and iron deficiency anaemia: clinico-endoscopical findings.
AB  - BACKGROUND: Iron deficiency anaemia (IDA) in men and postmenopausal women is
      mostly due to chronic gastrointestinal blood loss. One of the most common missed
      lesions while performing upper endoscopy in the work-up of IDA, are Cameron
      lesions, located at the neck of a large hiatal hernia. AIMS: Description of the
      bio-clinical and endoscopic findings of a large hiatal hernia, diagnosed in
      patients presenting with iron deficiency anaemia. Furthermore, a review of the
      literature concerning the diagnostic and therapeutic management of these patients
      will be outlined. STUDY: We retrospectively evaluated 36 patients, presenting
      with IDA (hemoglobin < 10 g/dl) associated with a large hiatal hernia. RESULTS:
      Cardiopulmonary complications of anaemia were the presenting symptoms, rather
      than gastrointestinal related complaints or bleeding. Cameron lesions were
      visualized only in 18 (50%) of our patients at their first presentation. There
      was no obvious correlation between the presence of Cameron lesions and visible
      gastrointestinal blood loss. Initially, almost all of our patients were treated
      medically. Seven underwent surgical repair of the hiatal hernia and all remained
      asymptomatic afterwards. CONCLUSION: We conclude that a hiatal hernia, with or
      without visible Cameron lesions, is a real and maybe underestimated cause of IDA.
      Finding a large hiatal hernia on upper endoscopy, together with a negative
      colonoscopy, completes the diagnostic work-up of IDA in most of these elderly
      patients. Currently, no guidelines concerning the optimal therapeutic management
      of this problem are available. Therapy may depend upon the need of transfusion,
      the efficiency of medical treatment, the risks of surgery and the preference and
      general condition of the patient.

PMID- 16279397
TI  - [The Lemierre syndrome: a complicated oropharyngeal infection].
AB  - The Lemierre syndrome or 'necrobacillosis' is a post angina sepsis caused by an
      acute oropharyngeal infection with a secondary thrombophlebitis of the internal
      jugular vein. There are often septic emboli in the lungs, although intestinal
      organs can also be affected. This syndrome is caused by the strictly anaerobic
      gram-negative pathogen Fusobacterium necrophorum, sometimes in combination with
      other pathogens. The patient typically presents with high fever, pain in the
      neck, malaise and dyspnoea one week after the start of an angina. Plain chest
      radiograph shows bilateral nodular infiltrates, ultrasound reveals a
      thrombophlebitis of the internal jugular vein. CT scan can be useful to confirm
      the diagnosis and possible complications. In the beginning there is often a
      transient hyperbilirubinemia with toxic inflammatory blood results. Under the
      correct antibiotic regime complete recovery can be obtained.

PMID- 16279398
TI  - Antimicrobial susceptibility of group B streptococci collected in two Belgian
      hospitals.
AB  - OBJECTIVE: to determine the in vitro susceptibility of group B streptococci (GBS)
      to antibiotics, used for intrapartum chemoprophylaxis and treatment of
      infections; to determine the rate of resistance to erythromycin and clindamycin
      and the phenotype distribution of GBS strains. METHODS: 262 GBS strains from
      pregnant women at 35-37 weeks' gestation were collected in University Hospital
      Gasthuisberg (Leuven) and Imelda Hospital (Bonheiden). The minimum inhibitory
      concentrations (MICs) of penicillin G, amoxicillin, cefazolin, cefotaxime,
      erythromycin, clindamycin, gentamicin, vancomycin and linezolid were determined
      by the agar dilution method, according to NCCLS guidelines. RESULTS: all isolates
      were susceptible to penicillin, amoxicillin, cefazolin, cefotaxime, vancomycin
      and linezolid. We found resistance rates of 16.7% to erythromycin and 11.0% to
      clindamycin. Of all erythromycin-resistant strains, 63.6% had the cMLSB
      phenotype, 20.5% the iMLSB phenotype and 15.9% the M-phenotype. For 25% of
      erythromycin-resistant strains, the resistance was of a very high level (MICs
      ranging from 128 microg/mL to 256 microg/mL). All these isolates belong to the
      cMLSB phenotype. For the remaining 75% the resistance to erythromycin was of low
      level (MICs ranging from 1 microg/mL to 4 microg/mL). These isolates had the
      cMLSB phenotype (38.6%), the iMLSB phenotype (20.5%) and the M-phenotype (15.9%).
      CONCLUSION: the susceptibility of GBS to the beta-lactam antibiotics supports the
      continued use of penicillin for intrapartum chemoprophylaxis. For women who are
      allergic to penicillin, clindamycin or erythromycin are considered to be the
      alternatives, however resistance rates to these antibiotics are significant.

PMID- 16279400
TI  - Macroprolactinemia: clinical significance and characterization of the condition.
AB  - The purpose of this study was to characterize the clinical picture of
      macroprolactinemic patients and to further assess whether macroprolactinemia was
      part of an auto-immune syndrome. Eighty-two hyperprolactinemic (serum PRL > 1000
      mU/l) patients were investigated and the PEG precipitation test identified 14
      patients with macroprolactinemia (bb PRL). They were submitted to a hormonal and
      autoimmune screening and an IV TRH test. Bioactivity of their serum prolactin was
      evaluated, using an Nb2 assay. The biochemical nature of bb-PRL was investigated
      by immunoprecipitation with anti-IgG antibodies. Seventy-nine percent of the
      studied patients presented with infertility, amenorrhoea, galactorrhoea,
      mastodynia, gynaecomastia or erectile dysfunction. In most cases, however, these
      symptoms could be explained by the presence of other non hyperprolactinemia
      related pathology. Despite the finding of in vitro biological activity in all
      macroprolactinemic sera tested, our results suggest a variable in vivo
      bioactivity of bb-PRL, probably related to a reduced capacity to cross vascular
      endothelium. In this study, we demonstrated that in 12 out of 13 samples (85%),
      bb-PRL consisted of PRL-IgG complexes. There was no clinical or laboratory
      evidence of auto-immunity.

PMID- 16279399
TI  - Timing of aortic valve replacement in elderly patients with symptomatic aortic
      valve disease using outpatient clinical parameters.
AB  - OBJECTIVE: To determine by how far worsening outpatient clinical parameters can
      affect outcome after aortic valve replacement, in patients with preserved left
      ventricular function and symptomatic aortic valve disease. PATIENTS AND METHODS:
      Five hundred patients with aortic valve disease underwent aortic valve
      replacement using a bioprosthesis. In 348 patients, another procedure was added.
      The preoperative outpatient parameters were investigated for their effect on
      hospital and long-term mortality. A Fisher exact, Kaplan-Meier univariate and Cox
      proportional hazard analysis were used. RESULTS: A retrospective follow-up of
      2022 patient years was obtained. Five preoperative parameters were found to be
      more present in patients with a decreased left ventricular function: 1) severity
      of symptoms, 2) previous myocardial infarction, 3) conduction defects, 4) aortic
      valve regurgitation and 5) increasing need for medication. In patients with an
      ejection fraction of 50% or more, logistic regression analysis showed that
      hospital mortality increased with need for medication (p=0.004), previously
      performed CABG (0.015), increase in symptoms (p=0.018) and myocardial infarction
      (p=0.034). A Kaplan-Meier analysis revealed aortic valve regurgitation (p=0.017)
      and increased need for medication (p=0.012) as significant on long-term survival.
      Presence of a previous myocardial infarction showed a trend (p=0.062). A Cox'
      proportional hazard analysis showed for global mortality increased need for
      medication (p=0.010) and previous myocardial infarction (p=0.018) as independent
      factors and for long-term mortality, this was aortic valve regurgitation
      (p=0.001). CONCLUSIONS: Results after aortic valve replacement deteriorate with
      the presence of valve regurgitation, a preoperative myocardial infarction,
      increasing need for medication or severity of symptoms, even for an ejection
      fraction of 50% or more. Anamnesis with special care to the degree of symptoms
      and increasing need for medication early in the valve disease could lead to early
      referral, thereby reducing number of patients with severe symptoms and improving
      postoperative results.

PMID- 16279401
TI  - Portal vein gas after concurrent chemoradiotherapy for advanced oesophageal
      carcinoma.
AB  - Portal vein gas is a rare but potentially lethal condition commonly caused by
      mucosal damage, bowel distention and sepsis. However, the association between
      portal vein gas and concurrent chemoradiotherapy has not been documented. We
      present the case of a 56-year old woman with portal vein gas revealed on computed
      tomography (CT) after concurrent chemoradiotherapy for advanced oesophageal
      carcinoma. The portal vein gas totally disappeared 10 days later without any
      specific treatment. This case demonstrates that the option of close observation
      for portal vein gas after concurrent chemoradiotherapy is appropriate for
      consideration. If physical examination, CT findings and laboratory data are
      unremarkable, it is essential that the patient undergoes close observation and
      repeated follow-up CT.

PMID- 16279402
TI  - Hypocalcemia: a rare complication of von Hippel-Lindau disease.
AB  - von Hippel-Lindau disease is a hereditary neoplastic syndrome, characterized by
      malignant and benign lesions in multiple organs. Pancreatic involvement is very
      common and is in general asymptomatic. We describe a case of malabsorption with
      severe hypocalcemia in a patient with von Hippel-Lindau disease, caused by
      exocrine pancreatic insufficiency, probably due to severe cystic transformation
      of the pancreas.

PMID- 16279403
TI  - Myopericarditis revealing adult-onset Still's disease.
AB  - We report the case of a 33 year-old man presenting with fever, arthralgias, sore
      throat, dyspnea and chest pain. Myopericarditis was diagnosed on the basis of
      electrocardiogram, echocardiography and cardiac magnetic resonance imaging (MRI).
      The dramatic increase in ferritinemia suggested the diagnosis of adult-onset
      Still's disease (AOSD), which could be established according to criteria of
      Yamaguchi. Rapid improvement occured under corticosteroids. Myocarditis is very
      rare in AOSD, pericarditis being more frequent. We report herein the first
      description of AOSD associated myocarditis evidenced by cardiac MRI.

PMID- 16279404
TI  - A revision of the descriptions of ectomycorrhizas published since 1961.
AB  - All available publications providing descriptions of ectomycorrhizas (ECM) were
      reviewed in order to build a database containing details on fungus forming the
      ECM, host tree, country where the material for description was collected, and
      habitat of the ECM. Other secondary data were also recorded. In all 1244
      descriptions of ECM published since 1961 in 479 papers were reviewed. The number
      of different ECM morphotypes described was 814. Most ECM described were collected
      in Europe and North America. Gymnosperms were the most common tree associates,
      and boreal and temperate forests the most studied ecosystems. Fungal symbionts
      were mostly Basidiomycota, epigeous, and with mushroom-like morphology. The paper
      also addresses the gaps in ECM knowledge that mycorrhizologists should address in
      future studies.

PMID- 16279405
TI  - Ectomycorrhizal mycobionts of Pisonia grandis on coral cays in the Capricorn
      Bunker group, Great Barrier Reef, Australia.
AB  - The diversity of ectomycorrhizal mycobionts of Pisonia grandis (Nyctaginaceae)
      from coral cays in the Capricorn-Bunker group, Great Barrier Reef, Australia, was
      examined. Only two ectomycorrhiza morphotypes (brown and black) were identified
      in soil from seven cays and DNA from both morphotypes was subjected to ITS-RFLP
      and sequence analysis. The brown morphotype was present in soil from all cays but
      the black morphotype was only observed in soil from three cays. ITS-RFLP analysis
      showed that the brown and black morphotypes were formed by different fungal taxa,
      with the RFLP pattern for the black morphotype being consistent with that of the
      culture previously obtained from black ectomycorrhizal roots on Heron Island.
      Comparison with the GenBank database revealed that closest matches to both
      morphotypes were sequences for various Thelephoraceae (Basidiomycota), but the
      brown and black morphotypes had only 80% sequence similarity to each other.
      Neighbour-joining analysis of these sequences with sequences for other
      Thelephoraceae grouped the brown and black morphotypes in a well-supported clade
      with several Tomentella species, suggesting that both belong to this genus. The
      data are discussed in relation to ectomycorrhizal fungal diversity and the coral
      cay habitat.

PMID- 16279406
TI  - Optional mitochondrial introns and evidence for a homing-endonuclease gene in the
      mtDNA rnl gene in Ophiostoma ulmi s. lat.
AB  - Strains of Ophiostoma ulmi, O. novo-ulmi subsp. americana, O. novo-ulmi subsp.
      novo-ulmi and O. himal-ulmi were examined for optional introns/insertions within
      the following mitochondrial genes: small subunit RNA gene (rns), large ribosomal
      subunit gene (rnl) and the cytochrome oxidase subunit I gene (coxI). Insertions
      were noted in the rns and coxI genes in strains of O. ulmi, the less aggressive
      species, but absent in strains of the more aggressive O. novo-ulmi subsp.
      americana. Strains of all species examined had a group I intron present in the
      U11 region of the mitochondrial-rnl gene. In all but two strains of O. novo-ulmi
      subsp. americana, this rnl-U11 intron was about 1.5 kb in length whereas a 2.6 kb
      version of this element was present in all strains representing O. ulmi, O. novo
      ulmi subsp. novo-ulmi, and Ophiostoma himal-ulmi. Irrespective of size, this
      intron based on RNA folds is a class IA1 group I intron and it encodes a putative
      ORF for the rps3 ribosomal protein. The size variation of the rnl-U11 intron was
      examined in detail for two strains of O. novo-ulmi subsp. americana and sequence
      data suggests the presence of a complex ORF within the 2.6 kb version of this
      intron; here a homing endonuclease-like gene has been inserted in frame and fused
      to the carboxyl-terminus of the putative rps3 coding region. The mitochondrial
      optional introns/insertions in combination with nuclear markers might be useful
      in distinguishing among the various species and subspecies of the O. ulmi s. lat.
      complex.

PMID- 16279407
TI  - Ophiostoma dentifundum sp. nov. from oak in Europe, characterized using molecular
      phylogenetic data and morphology.
AB  - Previous phylogenetic studies based on ITS sequence data have shown that
      Ophiostoma species with Sporothrix anamorphs include several species complexes.
      Isolates from oak in Poland and Hungary, which have previously been referred to
      as O. stenoceras, as well as isolates morphologically similar to S. inflata
      formed the basis of this study. Identification was based on sequences for the ITS
      region of rDNA operon and partial beta-tubulin gene. Analyses showed that
      isolates from Poland and Hungary reside in a well resolved clade, separate from
      those in the O. stenoceras-complex. The morphology of these isolates was compared
      with those of strains in the O. stenoceras complex and S. inflata. Morphological
      differences in teleomorph and anamorph structures were found between the isolates
      from Poland and Hungary and those in the O. stenoceras-complex. Growth
      characteristics and the presence of the teleomorph in culture could be used to
      separate this fungus from isolates in the S. inflata-complex. The fungus from
      Poland and Hungary is described here as O. dentifundum sp. nov. It is
      phylogenetically most closely related to isolates of S. inflata, which represent
      four well defined groups based on morphology and DNA sequence phylogeny.

PMID- 16279408
TI  - Phenotypic and DNA sequence data comparisons reveal three discrete species in the
      Ceratocystis polonica species complex.
AB  - Ceratocystis polonica and C. laricicola are two morphologically similar species
      that occur on conifers and reside in the Ceratocystis coerulescens species
      complex. They, however, represent two ecologically distinct entities. C. polonica
      causes blue stain on Norway spruce (Picea abies) and other spruce species (Picea
      spp.) in Eurasia and is associated with the bark beetles Ips typographus, I.
      typographus japonicus, I. amitinus and I. duplicatus. In contrast, C. laricicola
      lives in a symbiotic relationship with the bark beetles Ips cembrae and I.
      subelongatus that infest various larch species (Larix spp.). The objective of
      this study was to consider the phylogenetic relationships of C. polonica and C.
      laricicola and more specifically to determine the identity of Japanese isolates
      from both spruce and larch, based on sequences derived from the ITS regions of
      the rRNA operon, the beta-tubulin gene and the HMG box of the MAT-2 gene.
      Isolates were also compared based on morphology and cultural characteristics.
      Comparisons of anamorph and teleomorph structures confirmed that C. polonica and
      C. laricicola are indistinguishable based on morphology. Both species had an
      optimal growth temperature of 25 degrees C. However, at temperatures between 31
      33 degrees, C. polonica isolates grew slowly or not at all, while C. laricicola
      isolates grew more actively at these temperatures. Thus, a growth test at 32
      degrees can differentiate these species. Phylograms generated using parsimony for
      the three gene regions were strongly congruent. These showed three distinct
      clades supported by high bootstrap values. Two of the clades clearly separate C.
      laricicola from Europe and C. polonica, supporting the view that they represent
      two discrete taxa. A third clade included isolates obtained from galleries of Ips
      subelongatus on Larix kaempferi in Japan. This fungus clearly represents a
      discrete taxon that is closely related to, but distinct from C. laricicola, which
      is described here as C. fujiensis sp. nov.

PMID- 16279409
TI  - Taxonomic re-evaluation of Leptographium lundbergii based on DNA sequence
      comparisons and morphology.
AB  - The genus Leptographium was described in 1927 and currently includes 48 species,
      with L. lundbergii as the type species. In recent years, the taxonomic status of
      L. lundbergii has not been uniformly agreed upon and it has been the topic of
      considerable debate. The problem was compounded by the absence of a type
      specimen, and the species was epitypified at a later stage. Unfortunately, the
      whereabouts of the epitype is now unknown. In 1983, Wingfield & Marasas described
      L. truncatum, which is morphologically similar to L. lundbergii. Based on DNA
      comparisons and similarities in their morphology, this fungus was reduced to
      synonymy with L. lundbergii. The loss of the type specimen as well as variation
      in the morphology of strains identified as L. lundbergii prompted us to re
      examine the taxonomic status of this species. A number of strains from various
      geographic areas were studied. These include a strain of L. lundbergii deposited
      at CBS by Melin in 1929 (CBS 352.29) as well as the ex-type strain of L.
      truncatum. The strains were compared based on morphology and comparison of
      multiple gene sequences. Three genes or genic regions, ITS2 and part of the 28S
      gene, partial beta-tubulin and partial elongation factor 1-alpha were compared.
      Strains currently identified as L. lundbergii, represented a complex of species.
      Strains initially described as L. truncatum clustered separately from other L.
      lundbergii strains, could be distinguished morphologically and should be treated
      as a distinct taxon. L. lundbergii is provided with a new and expanded
      description based on a neotype designated for it. A third group was also
      identified as separate from the main L. lundbergii clade and had a distinct
      Hyalorhinocladiella-type anamorph, described here as H. pinicola sp. nov.

PMID- 16279410
TI  - Leptographium longiclavatum sp. nov., a new species associated with the mountain
      pine beetle, Dendroctonus ponderosae.
AB  - The mountain pine beetle, Dendroctonus ponderosae, and its fungal associates are
      devastating the lodgepole pine forests in British Columbia, Canada. During our
      fungal survey, an unknown Leptographium species has been consistently isolated
      from both D. ponderosae and infested lodgepole pine (Pinus contorta var.
      latifolia). This Leptographium species has similar morphology with the
      Leptographium anamorph of Ophiostoma clavigerum whose association with the D.
      ponderosae is well known. However, thorough morphological comparisons showed that
      this fungus is distinct from all the other Leptographium species described in the
      literature, and especially from O. clavigerum. Comparison of DNA sequences of
      multiple loci and the profiles by the PCR-RFLP marker also confirmed that this
      Leptographium species represents an undescribed taxon. Based on its distinct
      morphological, physiological characteristics and phylogenetic position, we
      describe it as L. longiclavatum sp. nov.

PMID- 16279411
TI  - Characterisation of manganese superoxide dismutase from Phytophthora nicotianae.
AB  - Three polypeptides with manganese superoxide dismutase (MnSOD) activity were
      found in mycelium, zoospores and germinated cysts of Phytophthora nicotianae.
      Their relative molecular weights in non-denaturing gels were approximately 34.5,
      36 and 50 kDa. No evidence for the presence of either iron or copper/zinc SODs
      was detected at any of the developmental stages examined. The level of activity
      of the MnSOD polypeptides was similar in mycelia and spores. Degenerate PCR was
      used to amplify partial genes of two different MnSODs, designated PnMnSODI and
      PnMnSOD2, from P. nicotianae. Southern blot analysis indicated that there are two
      PnMnSOD1 genes in the P. nicotianae genome. Full length sequence was obtained for
      one of these genes, PnMnSOD1a, from a P. nicotianae bacterial artificial
      chromosome (BAC) library. RNA blots probed with PnMnSOD1 showed similar levels of
      expression in vegetative and sporulating hyphae, lower levels in germinated cysts
      and no detectable expression in zoospores. PnMnSOD1a had 96%, 97 % and 99 % amino
      acid identity with homologous genes from P. ramorum, P. infestans and P. sojae,
      respectively. The second gene cloned from P. nicotianae, PnMnSOD2, had only 38 %
      amino acid identity with PnMnSOD1a and was homologous to MnSODs that possessed an
      N-terminal mitochondrial targeting sequence in Phytophthora species and other
      eukaryotes. Southern blots indicated that there is one copy of PnMnSOD2 in the P.
      nicotianae genome. PnMnSOD2 was expressed at similar levels in mycelia and
      germinated cysts but PnMnSOD2 transcripts were not detectable in zoospores.

PMID- 16279412
TI  - New PCR assay detects rare tooth fungi in wood where traditional approaches fail.
AB  - Lu et al. (2002) described a method for identifying Hericium species by PCR,
      using the primers HT-U1 and HT-L1 which they specifically designed for this
      purpose. In our hands these primers do not appear to discriminate between tooth
      fungi and other wood decay species. Therefore PCR primers were designed that
      discriminated Creolophus cirrhatus from other species (HER2F/HER3R), and which
      discriminate Hericium alpestre, H. coralloides and H. erinaceus from other wood
      decay Ascomycota and Basidiomycota but not from each other (HER2F/HER2R). Using
      the HER2F/HER3R primers together with traditional isolation and direct incubation
      procedures, the location of C. cirrhatus in Turkey oak logs was mapped. The PCR
      approach often detected C. cirrhatus in locations where it was suspected to be,
      based on patterns of staining and decay, but where it was not revealed by
      isolation onto agar media, emphasising the value of adopting several approaches
      to unravel fungal community structure in wood.

PMID- 16279413
TI  - Foraging behaviour of Armillaria rhizomorph systems.
AB  - The foraging behaviour of Armillaria rhizomorph systems is poorly understood
      owing to their cryptic position within the soil. We investigated foraging in a
      homogeneous environment (i.e. agar), finding that rhizomorph systems of the more
      parasitic species, A. mellea, A. ostoyae, and A. tabescens, lacked melanin and
      the approximately cylindrical cord-like form observed in the field. In contrast,
      rhizomorph systems of the more saprotrophic species, A. calvescens, A. gallica,
      and A. sinapina, developed radially resembling those in the field. For the three
      saprotrophic Armillaria species, the number of rhizomorph tips, total rhizomorph
      length and total rhizomorph surface area were significantly positively correlated
      with increasing rhizomorph system diameter and elapsed time in two developmental
      tests. However, the fractal dimension (D), used as a measure of foraging
      intensity, was temporally invariable, suggesting that one component of foraging
      behaviour is innate. In a heterogeneous environment (i.e. sand) and in the
      absence of a potential nutrient source, we observed that rhizomorph systems of A.
      gallica most often developed asymmetrically. While rhizomorph foraging was
      unresponsive to the lateral placement of an uncolonised stem segment, we were
      able to demonstrate directional growth toward an uncolonised Quercus velutina
      stem segment placed above or below the colonised source stem segment. When
      neighboring rhizomorph systems were conspecific genets of A. gallica, we observed
      that the growth of one rhizomorph system was directed toward zones unoccupied by
      its neighbour. However, the foraging intensity of the neighbouring genets, as
      measured by fractal dimension (D), was unaffected by the proximity of a
      neighbour. When neighbouring rhizomorph systems represented different species (A.
      gallica and A. mellea), A. gallica rhizomorph systems produced more total length
      and more foraging tips but concentrated their rhizomorph production away from the
      neighbouring A. mellea genet. In contrast, A. mellea rhizomorph systems produced
      significantly more foraging tips per unit length, both overall and in the zone of
      confrontation with the neighbouring A. gallica genet. Our observations are
      consistent with field observations of territoriality among Armillaria genets, and
      provide evidence that rhizomorph systems of more parasitic Armillaria spp. are
      able to compete effectively with the larger rhizomorph systems of more
      saprotrophic Armillaria species.

PMID- 16279414
TI  - Identification and characterization of Armillaria tabescens from the southeastern
      United States.
AB  - In the southeastern USA, Armillaria root rot disease on peach (Prunus persica) is
      caused by Armillaria tabescens, and to a lesser degree by A. mellea. Recent
      attempts to genetically characterize A. tabescens isolates using rDNA indicated
      the existence of heterozygosity in diploid isolates. In order to clarify this
      heterozygosity, DNA from stipe and single spore cultures of A. tabescens isolate
      SC.MF-1.01 was characterized using RFLP and sequence analysis. Direct sequencing
      of rDNA amplicons from diploid stipe tissue indicated heterozygosity in the IGS1
      and ITS2 regions. IGS1 copies A and B, and ITS copies A and B segregated in a 1:1
      ratio in single spore progeny, whereby IGS1 copy A always segregated with ITS
      copy A and IGS1 copy B always segregated with ITS copy B. The results indicate
      the existence of divergent haplotypes in the two nuclei of SC.MF-1.01 diploid
      mycelium and a single locus for rDNA tandem repeats. Additional IGS1 copies,
      designated IGS1 copy C, D, and E, with variable AluI restriction sites were
      cloned from SC.MF-1.01 diploid mycelium indicating polymorphism within ribosomal
      tandem repeats in A. tabescens. IGS1 copies C, D, and E were found once each in
      100 clones analyzed, and therefore seemed to be rare compared to copies A (44
      clones) and B (53 clones). RFLP and sequence analysis of the ribosomal IGS1 and
      ITS1 regions in North American A. tabescens isolates indicated that
      heterozygosity is common in A. tabescens diploid mycelium. A PCR-based molecular
      technique was developed to distinguish A. tabescens from many other North
      American Armillaria species, including A. mellea.

PMID- 16279416
TI  - Release and dispersal of basidiospores from Amanita muscaria var. alba and their
      infiltration into a residence.
AB  - Release and dispersal of basidiospores of Amanita muscaria var. alba and their
      potential to infiltrate a nearby residence were investigated. Basidiospore
      release mainly occurred in the first three days following the expansion of the
      caps. The concentrations of released basidiospores near basidiomata were 77 137,
      75 062, and 41 738 spores m(-3) in the first three days, respectively, with the
      highest concentration at 281 738 spores m(-3) air. After three days, the
      concentration dropped by 95%. At the second location, airborne basidiospore
      concentrations dropped 96-99% after three days with the concentrations of 940,
      575, and 1359 spores m(-3) in the first three days, respectively. The diurnal
      pattern showed a relatively extended night peak. Relative humidity and dew were
      positively correlated with basidiospore release and short distance dispersal.
      Rain and rain rate were positively correlated with basidiospore release, but not
      correlated with short distance dispersal. The basidiospore release period of
      Amanita muscaria var. alba was short, but within such a period it released a
      large amount of basidiospores. However, only less than 5% of basidiospores
      released were dispersed to the second location 5.2 m away and 2.7 m above the
      basidiomata. Only < 0.1% of basidiospores dispersed from the basidiomata were
      found inside a nearby residence. Amanita muscaria var. alba showed a low
      potential of infiltrating the residence.

PMID- 16279415
TI  - Phylogenetic analyses of DNA sequences reveal species partitions amongst isolates
      of Armillaria from Africa.
AB  - The basidiomycete genus Armillaria causes root rot and death to woody plants in
      boreal, temperate and tropical regions of the world. Armillaria root rot has been
      described from various parts of Africa on many different hosts. However, very
      little is known regarding the evolutionary relationships among Armillaria species
      in Africa. The aim of this study was to determine the phylogenetic relationships
      between isolates originating from different regions in Africa using nDNA
      sequences from two non-coding gene regions. The ITS and the IGS-1 regions of the
      ribosomal DNA operon were sequenced and analysed using different phylogenetic
      tree searching methods. Phylogenetic trees grouped the African taxa in two
      strongly supported clades. One of these represented A. fuscipes and the other an
      undescribed but distinct species.

PMID- 16279417
TI  - Andrastin A and barceloneic acid metabolites, protein farnesyl transferase
      inhibitors from Penicillium albocoremium: chemotaxonomic significance and
      pathological implications.
AB  - A survey of Penicillium albocoremium was undertaken to identify potential
      taxonomic metabolite markers. One major and four minor metabolites were
      consistently produced by the 19 strains surveyed on three different media.
      Following purification and spectral studies, the metabolites were identified as
      the known protein farnesyl transferase inhibitors andrastin A (1) and barceloneic
      acid A (2) along with barceloneic acid B (3), barceloneic lactone (4), and methyl
      barceloneate (5). These compounds are significant taxonomic markers for P.
      albocoremium; moreover this is the first report of a methyl ester of a
      barceloneic acid being produced as a secondary metabolite. Tissue extracts
      created following pathogenicity trials involving P. albocoremium and Allium cepa
      confirmed the production of these five metabolites in planta. Barceloneic acid B
      was found to be biologically active against a P388 murine leukemia cell line.

PMID- 16279418
TI  - Gjaerumia, a new genus in the Georgefischeriales (Ustilaginomycetes).
AB  - Teliospores, basidia, cultures, hyphal septations, cellular interactions and
      nucleotide sequences from the D1/D2 region of the nuclear large subunit ribosomal
      RNA gene of Entyloma ossifragi occurring on Narthecium ossifragum (Nartheciaceae)
      were examined and compared with findings in the Georgefischeriales and other
      Ustilaginomycetes. The data show that Entyloma ossifragi is a member of the
      Georgefischeriales. Among the Georgefischeriales, Entyloma ossifragi
      morphologically is very similar to Jamesdicksonia species, but differs from this
      genus and all other Georgefischeriales by the formation of dolipores without
      striations that become closed during teliosporogenesis. In addition, in our
      molecular phylogenetic analyses Entyloma ossifragi stands well apart from
      Jamesdicksonia, forming with some Tilletiopsis specimens a statistically
      supported cluster. Accordingly, the genus Gjaerumia gen. nov. and the family
      Gjaerumiaceae fam. nov. are proposed to accommodate Entyloma ossifragi in the
      Georgefischeriales. The new combination G. ossifragi (syn. Entyloma ossifragi) is
      made.

PMID- 16279419
TI  - New Asian species of the genus Anamika (euagarics, hebelomatoid clade) based on
      morphology and ribosomal DNA sequences.
AB  - Two dark-spored agaric species from Asia are placed in the genus Anamika
      (Agaricales or euagarics clade). This result is supported by ITS and nLSU-rDNA
      sequences with strong measures of branch support, in addition to several
      morphological and ecological similarities. An inclusive ITS study was performed
      using a mixed model Bayesian analysis that suggests the derived status of Anamika
      within Hebeloma, thereby rendering Hebeloma a paraphyletic genus. However, the
      monophyly of Hebeloma cannot be rejected outright given ITS and nLSU-rDNA data.
      Thus, we propose two new Asian species in Anamika: A. angustilamellata sp. nov.
      from dipterocarp and fagaceous forests of southwestern China and northern
      Thailand; and A. lactariolens comb. nov., a Japanese species originally described
      in the genus Alnicola. A complete description of A. angustilamellata, including
      illustrations, is provided.

PMID- 16279420
TI  - A new species of Hypocrella, H. macrostroma, and its phylogenetic relationships
      to other species with large stromata.
AB  - Two specimens of a new species of Hypocrella with large stromata were collected
      in Bolivia and Costa Rica. The morphology of the new species, H. macrostroma sp.
      nov., was compared with that of other species with large stromata, i.e. H.
      africana, H. gaertneriana, and H. schizostachyi. In addition, phylogenetic
      analyses of partial sequences from three genes, large subunit nuclear ribosomal
      DNA (LSU), translation elongation factor 1-alpha (EF1-alpha), and RNA polymerase
      II subunit 1 (RPB1), were conducted to determine the relationships of the new
      species to other species of Hypocrella/Aschersonia. Phylogenetic analyses show
      that H. macrostroma belongs to a strongly supported clade that includes H.
      africana, H. schizostachyi, and Aschersonia insperata, whereas other Hypocrella
      species belong to two sister clades. Hypocrella macrostroma is described and
      illustrated, and a lectotype is designated for H. gaertneriana.

PMID- 16279421
TI  - Phylogenetic analysis and real time PCR detection of a presumbably undescribed
      Peronospora species on sweet basil and sage.
AB  - Downy mildew of sweet basil (Ocimum basilicum) has become a serious disease issue
      for the producers of sweet basil in Switzerland since it was first recorded in
      2001. Reported in Africa in Uganda as early as 1933, major outbreaks of this
      disease in Europe were first noted in Italy in 1999 and in the USA from 1993.
      Previous reports have named the pathogen as Peronospora lamii. Its preferential
      hosts belong to the Lamiaceae family including basils (Ocimum spp.), mints (Menta
      spp.), sages (Salvia spp.) and other aromatics. This study investigated the
      taxonomic status of the downy mildew pathogen, using both morphological
      characters and molecular analysis of the ITS region of the rDNA. The inherent
      variability of conidial dimensions made species differentiation difficult.
      Sequence homology and phylogenetic analysis of nine collections of the
      Peronospora on sweet basil showed unique ITS sequences distinct from those of P.
      lamii and any other sequenced Peronospora species. This paper describes and
      illustrates the morphology of this presumably undescribed species of Peronospora.
      Its taxonomic position and relationships with other related species in the same
      genus are presented and discussed. In addition to this work, PCR primers for real
      time PCR analysis have been developed for the specific detection of this downy
      mildew pathogen from infected tissues or seeds. It is shown that these primers
      can also be used in classic PCR.

PMID- 16279422
TI  - Microcolonial rock inhabiting fungi and lichen photobionts: evidence for
      mutualistic interactions.
AB  - On nutrient-poor rock surfaces, yeast-like black fungi (also called microcolonial
      fungi, MCF) may derive organic carbon either from the atmosphere or from
      interactions with other rock-inhabiting microorganisms. Interactions between free
      living rock inhabiting heterotrophic fungi and phototrophic algae were
      investigated using axenic cultures. Five typical MCF strains were incubated with
      pure cultures of four lichen photobionts isolated from lichens growing in similar
      locations. After 2-12 months of combined cultivation, the fungal and algal
      colonies developed an overlapping structure involving both partners. Microscopic,
      histological and ultrastructural methods were used to investigate the changes
      that occur after prolonged contact. Histological analysis demonstrated changes in
      the spatial organisation of mixed colonies when in contact with each other. The
      branching of fungal hyphae was more pronounced in the vicinity of algal cells,
      thus increasing the potential contact surface. Photobiont cells were not changed
      in size, but a reduction of sporulation could be observed in some Trebouxia
      strains. Close cell wall contacts between fungal and algal cells were formed and
      mucilage accumulated at the contact places. The ability of MCF to form
      associations with potential photobionts present on rock surfaces was thus
      demonstrated for pure cultures in vitro.

PMID- 16279423
TI  - Colonization of cantaloupe roots by Monosporascus cannonballus.
AB  - Penetration of Monosporascus cannonballus into and growth within cantaloupe roots
      was studied using light and electron microcopy. Germ tubes penetrated the
      epidermis, and hyphae grew, without branching, almost directly to the xylem. The
      hyphae traversed the endodermis into protoxylem cells, and then grew extensively
      within the lumen of metaxylem vessels. Eventually, the hyphae grew back out into
      the cortical cells. A relatively low percentage of cells within both the cortex
      and xylem of lesions contained hyphae. The hyphae were generally localized within
      the lesion and could rarely be isolated more than 2 mm away from the margin of
      the lesion. Regardless of tissue type, hyphae were predominately intracellular.
      M. cannonballus appeared to be most similar to vascular wilt pathogens in its
      mode of parasitism, but does not spread via the vascular system to above-ground
      plant tissues.

PMID- 16279424
TI  - Development of a PCR-based diagnostic assay for the specific detection of the
      entomopathogenic fungus Metarhizium anisopliae var. acridum.
AB  - The entomopathogenic fungus Metarhizium anisopliae var. acridum is registered as
      a mycopesticide for acridid control in Africa and Australia. Traditionally,
      identification of M. anisopliae var. acridum infection in grasshoppers and
      locusts has relied upon development of fungal growth in infected cadavers.
      Conventional methods of detection of this entomopathogen in the environment and
      non-target organisms have been based on culture and bioassay. A PCR-based method
      for the detection of M. anisopliae var. acridum was developed. Sequence data from
      the distinct ITS rDNA regions facilitated the design of PCR primers that were
      used in PCR-based diagnostic assays for the detection of fungal DNA. The
      amplified sequence was 420 bp in length and specific to M. anisopliae var.
      acridum. Isolates of M. anisopliae var. anisopliae and M. flavoviride produced no
      PCR product with these primers. Other fungal entomopathogens, plant pathogens,
      mycopathogens, and soil saprophytes were also not detected by the pathogen
      specific primers. The assay was also effective for the detection of M. anisopliae
      var. acridum DNA in the presence of soil DNA extracts and in infected
      grasshoppers.

PMID- 16279425
TI  - TennCare medicaid program moving back to capitation.

PMID- 16279426
TI  - States move to capitation to reduce costs, improve quality and increase access.

PMID- 16279427
TI  - Physician organizations turn to care management.

PMID- 16279429
TI  - [Future possibilities of the multiple sclerosis treatment].
AB  - Multiple sclerosis is an autoimmune disease of the central nervous system.
      Pathogenetic mechanisms involve inflammation and neurodegeneration leading to
      myelin sheaths destruction and irreversible nerve fibre loss. At present mainly
      the inflammatory part can be influenced and undoubtedly only the earliest
      beginning of the treatment can effectively postpone irreversible disability. High
      dose corticosteroids remain the "gold standard" in MS attack treatment.
      Interferon beta and glatiramer acetate represent disease modifying drugs. Both of
      these medicaments decrease the number of attacks for about 30 %, however each
      patient responds differently. In many cases new attacks appear and it is
      necessary to intensify the treatment--to add immunosuppresives, to use
      combinations of steroid and cytostatic treatment. Intravenous immunoglobulins
      represent second line treatment. In the case of rapid disease progression
      immunoablation and stem cells transplantation is available. From recently tested
      drugs the most successful was the monoclonal antibody natalizumab. Unfortunately
      because of serious adverse effects in patients treated by combination of
      interferon beta + natalizumab, the application has been stopped. Monoclonal
      antibody against inteleukin 12 and chemokine receptor CCR2, cytostatics fumarate,
      laquinimod and cladribine are also tested in the clinical studies. DNA
      vaccination represents revolutionary opportunity of inducing tolerance against
      myelin autoantigens.

PMID- 16279428
TI  - [Purkinje's concept of a neuron].
AB  - With his experiments and findings J. Ev. Purkyne influenced 34 scientific
      disciplines; in some of them he is assumed to be their founder (embryophysiology,
      histology, pharmacological physiology, biophysics, comparative physiology). He
      was the pioneer in the field of neuroscience not only due to his neuroanatomical
      descriptions but namely due to his neurophysiological experiments. Beside the
      description of "Purkyne cells" and cells of other regions of the brain, Purkyne
      studied also the structure of neuronal processes and it is possible to attribute
      him the first description of dendrites. Existing material shows that Purkyne
      studied also the structure of hippocampus. Those and other papers prove that
      Purkyne recognised possible functional differences between various types of
      neurons and he speculated about their mutual relations. Only contemporary
      particularly detailed knowledge on the structure of hippocampal neuronal
      circuits, description of the mediator interaction and modulation together with
      the identification of neuroplastic processes in the hippocampus enable to
      accomplish the Purkyne's attempt to correlate the structure and function.

PMID- 16279430
TI  - [Aging eye--its specific features and diseases].
AB  - Practically oriented overview of the anatomical and physiological changes in the
      eye during aging is presented together with the description of diseases typical
      for the advanced age. The growing number of patients with eye diseases of
      advanced age and the comparatively low awareness of this fact within the medical
      community brought us to the publishing of the presented overview. It is necessary
      to increase the understanding of geriatric problems among ophthalmologists as
      well as to enhance the awareness of the age related changes in the eye during
      ageing among the physicians--non-ophthalmologists (namely among the general
      practitioners, internists, geriatrists) who treat seniors for other diseases.
      Namely they can meet in their everyday praxis the problems of drug interaction
      and the general and ophthalmologic side effects of various types of treatment.
      The use of ophthalmologic drugs (e.g. anti-glaucoma remedies) is connected with
      undesirable effects on the organism in any age and namely in elderly patients.

PMID- 16279431
TI  - [Lung cancer operability--history and presence].
AB  - Review of contemporary publication on the operability of lung cancer in the Czech
      Republic and in other countries is presented. Since 1912, when 374 cases of lung
      cancer were described, the incidence has risen and culminated towards the end of
      the 20th century. From the available treatment modalities, surgery gives the best
      results. An overview of papers describing the beginning of thoracic surgery in
      the Monde and in the Czech Republic is given. In the Czech Republic during 2002,
      11.3% of all lung cancers were resected. From the TRN clinics in the Czech
      Republic about 20 to 27% of patients are recommended. In the leading world
      centres the operability is higher--about 25 to 35% of patients. The improvement
      of operability of lung cancer is possible namely by the increase of timely
      diagnosed tumors and by more frequent use of neoadjuvant medication in the
      treatment algorithms.

PMID- 16279432
TI  - [Intermittent catheterization of urinary bladder--indications, technique,
      complications].
AB  - The intermittent catheterization technique is considered at present to be one of
      pillars of the therapy of lower urinary tract dysfunction. The technique
      gradually became used also in the treatment of some non-neurogenic voiding
      dysfunctions. There are many ways, how the intermittent catheterization could be
      performed (methodology, catheter material and type, lubrication type and method,
      catheterization frequency). Authors provide an overview of present indications to
      use the treatment; they describe individual techniques and draw attention to the
      possible complications and their solution. Next they emphasize the necessity of
      individual approach to intermittent catheterization technique in individual
      patients in the broader context of general concept of treatment.

PMID- 16279433
TI  - [Time perception in functional brain imaging].
AB  - BACKGROUND: Knowledge of physiological mechanisms underlying time perception is
      still rather limited. The aim of our study was to search for a 'time
      accumulator', i.e. the part of the brain where information on the duration of
      time is stored. METHODS AND RESULTS: Nine healthy volunteers were given a time
      reproduction task during event-related fMRI. Subjects were instructed to retain
      the duration of the stimulus presented (presentation phase) and then to reproduce
      it by pressing a button (reproduction phase). Two different analyses were made:
      event-related (P < 0.05, FWR corrected) and parametric (BOLD signal
      increase/decrease during the presentation/reproduction phases correlated with the
      time intervals; P < 0.01, FDR corrected). When the event-related approach was
      employed, activation was noted bilaterally in the inferior prefrontal cortex
      (IPFC), supplementary motor area (SMA), precuneus and secondary visual cortex. On
      the right, there was activation in the dorsolateral prefrontal cortex (DLPFC),
      gyrus cinguli and inferior parietal lobule. On the left, the primary sensory
      motor cortex was activated. While during the presentation phase the left DLPFC
      activity inversely correlated with the presented duration, a nearly identical
      area showed positive correlation in the reproduction phase. CONCLUSIONS: The
      event-related analysis did not allow distinguishing the process of time
      perception from many cognitive processes running simultaneously. In turn, the
      parametric analysis was based on visualizing regions, in which the signal
      correlated with the varying duration of the time interval provided the level of
      attention, decision-making and the processes of behavioral response planning and
      execution were constant. Moreover, the right and left DLPFC seem to play
      different roles in time perception. While the left one is functioning as a "time
      accumulator", the right one is rather involved in the recognition of previously
      perceived intervals.

PMID- 16279435
TI  - [Periodic limb movements in sleep: polysomnographic and actigraphic methods for
      their detection].
AB  - BACKGROUND: The aim of our study was to compare the results obtained by
      simultaneous polysomnographic and actigraphic recording and thus to estimate the
      specificity and sensitivity of actigraphic evaluation of periodic leg movements
      in sleep (PLMS). As a standard method, PLMS are detected by means of
      polysomnography, including superficial EMG of anterior tibial muscles. Since
      1995, there have been efforts to detect PLMS by means of actigraphy, which is
      more convenient for both patient and investigator. METHODS AND RESULTS:
      Recordings were done during 44 nights in 42 patients (10 women, mean age 49.2, SD
      13.1 years) in our sleep laboratory. The same criteria for periodic leg movements
      and the cut-off periodic leg movements index (PLMI > 5) were used in both
      methods. For the actigraphic way of PLMS detection, we found a specificity of
      90%, sensitivity 60%, positive predictive value 88.2%, negative predictive value
      64.3 % and total diagnostic accuracy of 73.3%. A close correlation (Spearman's
      coefficient rho > 0.64, p < 0.0001) between PLMI resulting from either method of
      recording was observed, though the PLMI actigraph proved to be significantly
      lower (Sign test--p < 0.01). CONCLUSIONS: Our study has proven good specificity a
      negative predictive value of the actigraphic recording. To improve its
      sensitivity, we suggest to reduce the threshold of significant presence PLMS, as
      expressed by PLMI, from 5 to 3. Actigraphy seems to be a suitable method from
      PLMS screening in the general population for both clinical and research purposes.

PMID- 16279434
TI  - [Heart rate variability during sleep].
AB  - BACKGROUND: Changes in the tone of the autonomic nervous system during sleep
      occur and characterize individual sleep stages and probably also sleep cycles.
      The spectral analysis of the heart rate variability (SA HRV) is a tool for exact
      assessment of autonomic nervous activity giving us precise information on the
      activity of the autonomic nervous system--on its sympathetic and parasympathetic
      component. METHODS AND RESULTS: All night polysomnographic recording was
      performed in 11 healthy subjects, during which the SA HRV was carried out. The
      total spectral power of the heart rate variability and relative values of its
      individual components were evaluated: the very low frequency component (VLF), the
      low frequency component (LF), and high frequency component (HF). The absolute
      value of the RR-interval duration was assessed. The LF spectral band in
      normalized units was significantly higher during REM sleep than in non-REM sleep.
      On the other hand, the HF spectral band in normalized units was significantly
      higher during non-REM sleep compared to REM sleep. The LF/HF ratio, which
      reflects the sympathovagal balance, had a maximal value during REM sleep and
      reached its minimum in non-REM sleep. A gradual lengthening of the RR-interval
      and lowering of the LF/HF ratio during night was observed. CONCLUSIONS: The SA
      HRV showed to be a sensitive method for detection of activity of the autonomic
      nervous system during sleep. The sympathovagal balance was shifted to prevailing
      sympathetic activity in REM sleep. On the contrary, during non-REM sleep this
      balance was shifted towards prevailing parasympathetic influence. A gradual
      increase of parasympathetic influence during night was also observed.

PMID- 16279436
TI  - [Alternating hemiplegia of childhood (AHC)].
AB  - BACKGROUND: Alternating hemiplegia of childhood (AHC) is a rare neurological
      disease of unknown aetiology characterized by recurrent paroxysmal attacks of
      side-alternating hemiplegias of variable duration associated with other
      paroxysmal dysfunctions. Paroxysmal attacks start in infants but neurological
      deficits become progressive with the age. METHODS AND RESULTS: During the last 20
      years 8 patients (5 boys, 3 girls) with AHC were followed. Mean age at the time
      of diagnosis was 2.75 years, age range 2-5 years; mean follow up period 13.9
      years (range 1 month-20 years) The diagnosis was based on clinical history and
      neurological findings, completed by neurophysiological and neuroimaging methods
      (SPECT, PET), and results of psychological and biochemical findings. Paroxysmal
      phenomena (occulo-motor, tonic, choreo-athetotic, autonomic) appearing at the age
      of 4.1 +/- 2.2 months and followed by repeated attacks of hemiplegia (age onset
      16.3 +/- 13.0 months) were the first symptoms. Progressive neurological
      impairment covering spasticity, dyskinetic syndrome, cerebellar ataxia and
      intellectual deficit was present in all cases, epileptic seizures in 7 out of 8
      patients. On ictal SPECT/PET examination hypoperfusion/glucose hypometabolism
      were demonstrated above affected hemispheres including basal ganglia, both
      thalami and cerebellar hemispheres. Improvement of hemiparesis was illustrated by
      nocturnal videomonitoring. CONCLUSIONS: AHC is a chronic disease with progressive
      neurological deficit. A flunarizine therapy has a favorable effect on frequency
      and severity of paroxysmal attacks, but does not prevent a progressive
      neurological impairment.

PMID- 16279437
TI  - [Embolism of the upper mesenteric artery].
AB  - The article presents a case report of a 53-year-old man, who underwent abdominal
      surgery for the ischemic vascular necrosis of the small bowel and right colon of
      the embolic aetiology and who has had several serious comorbidities. Resection of
      the major part of the small bowel and right hemicolectomy with high jejunostomy
      and transversostomy was performed. Not only has the patient very well tolerated
      the first surgery, but he tolerated also the other one with recovery of passage
      continuity. The other surgery was necessary due to mycotic infection in the right
      atrium (vegetations at the heart pacing electrode). After 5 months the patient
      died because of generalisation of mycotic infection. The problem of mesenteric
      vascular occlusions is discussed.

PMID- 16279438
TI  - [Treatment of juvenile pemphigus vulgaris with intravenous immunoglobulins].
AB  - Juvenile pemphigus vulgaris (JPV) is a rare autoimmune disease. It is treated by
      different immunosuppressive drugs, which may have serious side effects. Such
      problems are most apparent in the therapy of children and adolescents. The use of
      intravenous immunoglobulins (IVIG) is a safe and effective method and therefore
      it can replace or at least postpone the initiation of the combined
      immunosuppressive therapy. The article reports experience with the IVIG therapy
      of severe JPV in 16-year-old female patient. The double combination of IVIG and
      prednisone was used. IVIG were administered in a dose of 400 mg/kg/day during
      three consecutive days with the intervals of 1-2 months. Totally 5 cycles were
      applied. The therapeutic effect was excellent, it started within few days, but it
      was only temporary and lasted for 1-2 months. IVIG therapy enabled the dose of
      prednisone to be reduced from 50 mg/day to 15 mg/day. Following the cessation of
      IVIG, the double combination therapy of prednisone and azathioprine was
      initiated, but it was unsuccessful in controlling the disease. Remission of JPV
      achieved with triple combination of prednisone (25 mg/day), azathioprine (100
      mg/day) and dapsone (50 mg/day) was comparable to that of IVIG and prednisone
      combination. On the basis of their positive experience the authors recommend to
      use IVIG also for cases of childhood and juvenile pemphigus, in which this
      therapy can delay the need for administration of immunosuppressive drugs with
      potential of serious adverse effects.

PMID- 16279440
TI  - [How many pathological gamblers are in the Czech Republic?].
AB  - The number of pathological gamblers in the Czech Republic is not known. Every
      10th male adolescent 18-year-old gambles once a month or more often. The number
      of slot machines in the Czech Republic is 1 per 200 of residents. Considering the
      prevalence of pathological gambling in other countries, we estimate that the
      prevalence of pathological gambling in the Czech Republic is probably not lower
      than 0.5-1% of population. Many more people are affected indirectly (family
      members and the victims of gambling related crimes). Effective prevention should
      both decrease availability and the demand.

PMID- 16279439
TI  - [Alcohol and pregnancy].
AB  - Alcohol abuse in pregnancy causes fetal alcohol spectrum disorders ranging from
      discreet developmental problems to fetal alcohol syndrome. That is why pregnant
      women and the women considering pregnancy should abstain from alcohol. Fetal
      alcohol spectrum disorders occur even after drinking at early stages of pregnancy
      when women are not aware of being pregnant. According to one study 75% Czech
      women drank alcohol before pregnancy and one third of them continued during first
      three months of pregnancy. According to new epidemiological data 83.4% of Czech
      women aged between 18 and 40 drank alcohol during the year preceeding the
      pregnancy. The prevention in this area in the Czech Republic is clearly not
      satisfactory, and it is complicated by the alcohol advertising targeted at women,
      low taxation of alcohol and other factors.

PMID- 16279441
TI  - [A hitherto unknown priority of Jan Ev. Purkyne--myocardial sleeves of the
      pulmonary veins. Contribution to the pathogenesis of atrial fibrillation].
AB  - According to recent electrophysiological discoveries, atrial fibrillation is
      triggered by ectopic beats which in most cases originate in the pulmonary veins,
      in extensions of left atrial myocardium upon these veins, so called myocardial
      sleeves. In the relevant literature it is stated that this anatomical structure
      was first described by Ferdinand Raeuschel in 1836 in the publication "De
      arteriarum et venarum structura". This publication appeared as Raeuschel's
      dissertation thesis at the faculty of medicine in Breslau (now Polish Wroclaw) at
      the department of physiology under the leadership of Jan Ev. Purkyne. In the
      introduction, the author thanks his tutor for introducing him into the
      problematic and for the continuous help, stating that all new discoveries in the
      dissertation should be ascribed to Purkyne. Thus, the description of myocardial
      sleeves of pulmonary veins appears as a yet further priority of the great Czech
      scientist.

PMID- 16279442
TI  - Spatial information transmission using orthogonal mutual coherence coding.
AB  - We use the coherence of a light beam to encode spatial information. We apply this
      principle to obtain spatial superresolution in a limited aperture system. The
      method is based on shaping the mutual intensity function of the illumination beam
      in a set of orthogonal distributions, each one carrying the information for a
      different frequency bandpass or spatial region of the input object. The coherence
      coding is analogous to time multiplexing but with multiplexing time slots that
      are given by the coherence time of the illumination beam. Most images are static
      during times much longer than this coherence time, and thus the increase of
      resolution in our system is obtained without any noticeable cost.

PMID- 16279443
TI  - Far-zone approximation for partially coherent sources.
AB  - A general condition is derived for the distance beyond which the far-zone
      approximation can be used in studying propagation of light from a partially
      coherent source. The distance steadily increases as a function of the coherence
      radius across the source, reaching the usual value in the coherent limit.

PMID- 16279444
TI  - Bayesian approach to non-Gaussian field statistics for diffusive broadband
      terahertz pulses.
AB  - We develop a closed-form expression for the probability distribution function for
      the field components of a diffusive broadband wave propagating through a random
      medium. We consider each spectral component to provide an individual observation
      of a random variable, the configurationally averaged spectral intensity. Since
      the intensity determines the variance of the field distribution at each
      frequency, this random variable serves as the Bayesian prior that determines the
      form of the non-Gaussian field statistics. This model agrees well with
      experimental results.

PMID- 16279446
TI  - Design principles of multifiber resonant directional couplers with hollow Bragg
      fibers: example of a 3 x 3 coupler.
AB  - When several hollow photonic crystal fibers (HPCFs) are placed in proximity to
      each other, radiation-induced interfiber coupling between their core guided modes
      is observed. Under certain conditions coupling between the core modes of two
      touching collinear fibers can have a resonant increase via excitation of a low
      quality intermirror cavity resonant state. Such coupling, however, decreases
      dramatically within the first micrometer of intermirror separation. Moreover,
      when fibers are touching, in the frequency domain a large number of accidental
      degeneracies with fiber surface and mirror states complicate the design of a
      stable 2 x 2 coupler. To alleviate these problems we consider coupling among
      three hollow Bragg fibers. When placed in the vertices of an isosceles triangle,
      even for a finite separation between fibers, triangular interfiber cavity forms a
      high-quality resonator that can be tuned via additional structural elements to a
      particular frequency of interest. Interfiber surface states are suppressed by
      keeping the fiber separation finite, thus allowing stable coupling conditions in
      a 3 x 3 HPCF coupler configuration.

PMID- 16279445
TI  - Generation of optical vector beams with a diffractive optical element
      interferometer.
AB  - We present a novel approach to generating radially and azimuthally polarized
      vector beams that utilize an interferometer constructed from two identical
      diffractive optical elements. The measured polarization properties of four vector
      beam states and their phase relationships are in good agreement with theoretical
      expectations. This interferometer is passively phase stable and robust, making it
      suitable for linear and nonlinear optical (superresolution) microscopy.

PMID- 16279447
TI  - Passive mode locking at harmonics of the free spectral range of the intracavity
      filter in a fiber ring laser.
AB  - We report the passive mode-locking at harmonics of the free spectral range (FSR)
      of the intracavity multi-channel filter in a fiber ring laser. The laser uses a
      sampled fiber Bragg grating (SFBG) with a free spectral range (FSR) of 0.8 nm, or
      99 GHz at 1555 nm, and a length of highly nonlinear photonic crystal fiber with
      low and flat dispersion. Stable picosecond soliton pulse trains with twofold to
      sevenfold enhancement in the repetition rate, relative to the FSR of the SFBG,
      have been achieved. The passive mode-locking mechanism that is at play in this
      laser relies on a dissipative four-wave mixing process and switching of
      repetition rate is realized simply by adjustment of the intracavity polarization
      controllers.

PMID- 16279448
TI  - Breaking the limit of maximum effective area for robust single-mode propagation
      in optical fibers.
AB  - We propose and demonstrate a novel approach in optical fiber design in which the
      optical waveguide is formed by a ring of large air holes surrounding a solid
      silica core. With an appropriate choice of the geometrical configuration, robust
      single-transverse-mode propagation with a record effective area of 1417 microm2,
      verified by various methods, was demonstrated. A breakthrough was made toward the
      development of practical ultra-high-power fiber lasers as we observed negligible
      loss of the fiber at bending diameters as small as 15 cm.

PMID- 16279449
TI  - Self-aligning method of fiber-to-waveguide pigtailing.
AB  - An innovative self-aligning technique for the pigtailing of optical fibers to
      buried channel planar waveguides is presented, based on selective etching. This
      technique utilizes a plug-and-socket mechanism that is intrinsically self
      aligning and mechanically stable. The processes involved have been specifically
      designed to facilitate the bulk manufacture of pigtailed single or multiple
      fibers and waveguides. An optimized alignment geometry for the physical
      connection of fibers to waveguides is presented.

PMID- 16279450
TI  - All-optical flip-flop based on an active Mach-Zehnder interferometer with a
      feedback loop.
AB  - A novel architecture for an all-optical flip-flop is validated experimentally.
      The architecture comprises a single semiconductor optical amplifier-based Mach
      Zehnder interferometer with an external feedback loop. The experimental results
      show optical bistable operation for a latching device with an on-off contrast
      ratio of 11 dB that employs set and reset pulses of less than 250 pJ, although
      the energy of these pulses could be greatly reduced by optical integration of the
      whole device.

PMID- 16279451
TI  - Lifting polarization degeneracy of modes by fiber design: a platform for
      polarization-insensitive microbend fiber gratings.
AB  - Polarization dependence in microbend gratings is an inherent problem, even in
      perfectly circular fibers, since antisymmetric modes are almost degenerate linear
      combinations of four distinct, polarization-sensitive modes. We demonstrate a
      novel fiber design that lifts polarization degeneracies of the antisymmetric
      modes to solve this problem. By intentionally exacerbating the polarization
      splittings, we achieve coupling to only the polarization-insensitive doublet,
      over wavelength ranges exceeding 100 nm, thus demonstrating a device with
      practical usable bandwidths. This allows all previous applications envisaged with
      UV-induced long-period gratings to be realized with the significantly lower-cost
      microbend technology platform.

PMID- 16279452
TI  - Multiwavelength laser light transmission of hollow optical fiber from the visible
      to the mid-infrared.
AB  - We report on low-loss multiwavelength laser delivery of hollow optical fiber in a
      wide wavelength region, from the visible to the infrared. Improved methods of
      liquid-phase coating were used to fabricate the hollow fiber with inner films of
      a silver and a cyclic olefin polymer (COP) layer. The surface roughness of the
      silver layer was reduced dramatically by pretreatment on the inner glass surface
      with an SnCl2 solution. The COP layer roughness was also decreased by using an
      ambient atmosphere of tetrahydrofuran (THF) solvent during the COP layer
      formation. Owing to the smooth surfaces, hollow fiber with optimum COP film
      thickness for CO2 laser light simultaneously yields low losses for a Er:YAG laser
      and a red pilot beam. The power durability of CO2 and Er:YAG lasers, as well as
      the loss properties for the pilot beam, is demonstrated.

PMID- 16279453
TI  - Model-based processing of a holographic moire.
AB  - A state space model for the determination of dual phase distributions in a
      holographic moire in the presence of nonsinusoidal waveforms, random noise, and
      miscalibration of the piezoelectric (PZT) devices is proposed. The extraction of
      these phase terms requires incorporating two PZTs into the moire setup. A
      Toeplitz approximation method (TAM) is applied for phase determination, and
      modification to the Toeplitz covariance matrix formed from the phase-shifted
      moire fringes by application of a denoising step in the state-feedback matrix is
      proposed. This step ensures that the phase terms can even be estimated at a
      signal-to-noise ratio much lower than that of the original TAM or by our
      previously suggested polynomial based method.

PMID- 16279454
TI  - Determination of curvature and twist by digital shearography and wavelet
      transforms.
AB  - A new technique based on digital shearography for determining the transient
      curvature and twist of a continuously deforming object from a series of speckle
      patterns is presented. The intensity variation of each pixel is analyzed along
      the time axis by using a complex Morlet wavelet transform. The absolute sign of
      the phase variation is determined by introduction of a temporal carrier when the
      speckle patterns are captured by a high-speed camera. A high-quality spatial
      distribution of the deflection derivative is extracted at any instant without the
      need for temporal or spatial phase unwrapping. The continuous Haar wavelet
      transform is subsequently processed as a differentiation operator to reconstruct
      the instantaneous curvature and twist of a continuously deforming object.

PMID- 16279455
TI  - Broadband nulling of a vortex phase mask.
AB  - A pulse transmitted through a helical vortex phase mask undergoes a temporal
      Hilbert transform. The fluence transmitted into the unfavorable plane wave mode
      is found to increase as the square of the bandwidth and, to first order, is
      independent of the topological charge.

PMID- 16279456
TI  - Double-pass axially resolved confocal Mueller matrix imaging polarimetry.
AB  - We present experimental depth-resolved complete polarization-sensitive
      measurements of a stack of linear retarders and glass plates by using what is to
      the best of our knowledge the first combination of a confocal imaging system with
      a complete Mueller matrix polarimeter. The axially resolved Mueller matrices were
      compared with a forward simulation, with good agreement.

PMID- 16279457
TI  - Remote imaging laser-induced breakdown spectroscopy and remote cultural heritage
      ablative cleaning.
AB  - We report, for what we believe to be the first time, on remote imaging laser
      induced breakdown spectroscopy (LIBS). Measurements have been performed by using
      a tripled Nd:YAG laser working at 355 nm with 170 mJ pulse energy, with an
      expanded beam that is focused onto a target at 60 m distance. The LIBS signal is
      detected by using an on-axis Newtonian telescope and an optical multichannel
      analyzer. The imaging is performed by scanning the laser beam on the target. The
      same setup is also used in demonstrations of remote laser ablation for cleaning
      of contaminated objects with applications toward cultural heritage.

PMID- 16279458
TI  - Observation of amplitude and phase in ridge and photonic crystal waveguides
      operating at 1.55 microm by use of heterodyne scanning near-field optical
      microscopy.
AB  - We apply heterodyne scanning near-field optical microscopy (SNOM) to observe with
      subwavelength resolution the amplitude and phase of optical fields propagating in
      several microfabricated waveguide devices operating around the 1.55 microm
      wavelength. Good agreement between the SNOM measurements and predicted optical
      mode propagation characteristics in standard ridge waveguides demonstrates the
      validity of the method. In situ observation of the subwavelength-scale
      distribution and propagation of optical fields in straight and 90 degrees bend
      photonic crystal waveguides facilitates a more detailed understanding of the
      optical performance characteristics of these devices and illustrates the
      usefulness of the technique for investigating nanostructured photonic devices.

PMID- 16279459
TI  - Fabrication of multimode interference waveguides in glass by use of a femtosecond
      laser.
AB  - We report on the fabrication of multimode interference (MMI) waveguides that
      split single-mode light into multimode light in synthesized silica by use of
      femtosecond laser pulses. The number of modes at the output facet is dependent on
      both the width and the length of the MMI waveguides. The output spectral
      responses of the MMI waveguides in the visible region were examined. The
      fabricated MMI waveguides can be used as compact power splitters with large fan
      outs.

PMID- 16279460
TI  - Ultrafast all-optical modulation on a silicon chip.
AB  - We experimentally demonstrate ultrafast all-optical modulation using a micrometer
      sized silicon photonic integrated device. The device transmission is strongly
      modulated by photoexcited carriers generated by low-energy pump pulses. A p-i-n
      junction is integrated on the structure to permit control of the generated
      carrier lifetimes. When the junction is reverse biased, carriers are extracted
      from the device in a time as short as 50 ps, permitting greater than 5 Gbit/s
      modulation of optical signals on a silicon chip.

PMID- 16279461
TI  - Diffraction engineering in arrays of photonic crystal waveguides.
AB  - Light propagation in uniform arrays of photonic crystal waveguides is studied. We
      demonstrate that, in stark contrast to the case of conventional waveguide arrays,
      diffraction can be tailored both in magnitude and sign by varying only the
      spacing between adjacent waveguides. Diffraction management in ultracompact
      arrays of straight photonic crystal waveguides is demonstrated by solving
      Maxwell's equations through the time-domain finite-element method.

PMID- 16279462
TI  - Design and analysis of mach-Zehnder interferometer sensors based on dual strip
      antiresonant reflecting optical waveguide structures.
AB  - Mach-Zehnder interferometer sensors based on dual strip antiresonant reflecting
      optical waveguide (ARROW) structures are proposed. By adjusting the degree of
      structural symmetry to control the coupling behavior of the dual strip ARROW, an
      interferometric sensor without any bending structures can be realized. Operating
      principles and an analysis of the device are discussed in detail.

PMID- 16279463
TI  - Integrated all-optical pulse regenerator in chalcogenide waveguides.
AB  - We report a fully integrated, passive, all-optical regenerator capable of terabit
      per second operation, based on a highly nonlinear chalcogenide (As2S3) glass rib
      waveguide followed by an integrated Bragg grating bandpass filter. We demonstrate
      a clear nonlinear power transfer curve with 1.4 ps optical pulses, capable of
      improving the signal-to-noise ratio and reducing the bit error rate for digital
      signals.

PMID- 16279464
TI  - Two-mode injection locking in vertical-cavity surface-emitting lasers.
AB  - We report on the dynamics that accompany polarization switching induced by
      orthogonal optical injection in a vertical-cavity surface-emitting laser (VCSEL).
      As the injection strength increases, the VCSEL bifurcates to injection-locked
      steady states and time-periodic and possibly chaotic dynamics. Of particular
      interest is a two-mode injection-locking solution, i.e., locking of the two VCSEL
      polarization modes. A detailed stability analysis unveils new bistability
      mechanisms in optical injection problems.

PMID- 16279465
TI  - High-power Yb-doped multicore ribbon fiber laser.
AB  - A highly elongated double-clad ribbon fiber that comprises a pure-silica inner
      cladding with transverse dimensions of approximately 1.4 mm by 0.23 mm with a
      linear array of ten ytterbium-doped cores has been fabricated and operated in a
      simple laser configuration pumped by two diode stacks. The fiber laser yielded
      320 W of output power at a center wavelength of 1045 nm in a combined beam with
      beam propagation factors of approximately 2 (perpendicular to the array) and
      approximately 150 (parallel to the array) for 576 W of launched pump power. The
      slope efficiency with respect to absorbed pump power was 62%. The prospects for
      further power scaling and improved beam quality and efficiency are discussed.

PMID- 16279466
TI  - Distributed-feedback terahertz quantum-cascade lasers with laterally corrugated
      metal waveguides.
AB  - We report the demonstration of distributed-feedback terahertz quantum-cascade
      lasers based on a first-order grating fabricated via a lateral corrugation in a
      double-sided metal ridge waveguide. The phase of the facet reflection was
      precisely set by lithographically defined facets by dry etching. Single-mode
      emission was observed at low to moderate injection currents, although multimode
      emission was observed far beyond threshold owing to spatial hole burning. Finite
      element simulations were used to calculate the modal and threshold
      characteristics for these devices, with results in good agreement with
      experiments.

PMID- 16279467
TI  - Spectral derivative based image reconstruction provides inherent insensitivity to
      coupling and geometric errors.
AB  - A reconstruction algorithm for multiwavelength diffuse optical tomography is
      presented, where instead of using data at each wavelength separately or even
      simultaneously, the difference in data for multiple wavelength pairs is used to
      reconstruct absolute concentration maps of chromophores. The results indicate a
      dramatic improvement in image reconstruction and the elimination of image
      artifacts, which are often associated with unknown measurement errors such as
      coupling coefficients and external boundary variations, because these errors are
      often less dependent on wavelength, and are effectively removed from the data set
      of the first derivative of intensity with respect to wavelength.

PMID- 16279469
TI  - High-energy quasi-phase-matched optical parametric oscillation in a periodically
      poled MgO:LiNbO3 device with a 5 mm x 5 mm aperture.
AB  - Fabrication of a 5 mm thick periodically poled MgO-doped LiNbO3 device with a
      32.1 microm period for mid-infrared generation was demonstrated. The periodic
      structure was evaluated by measurement of second-harmonic generation with the d31
      coefficient. Optical parametric oscillation using this device with an uncoated 5
      mm x 5 mm aperture and a 36 mm effective length realized a high-energy output of
      77 mJ for both signal (wavelength 1.83 microm) and idler (2.54 microm) waves with
      a 72% slope efficiency at 110 mJ pumping of a Q-switched Nd:YAG laser with a 12
      ns pulse duration.

PMID- 16279468
TI  - Diffuse optical measurement of blood flow in breast tumors.
AB  - Blood flow contrast between tumor and normal tissues in patients with malignant
      and benign breast cancer was measured by diffuse optical correlation methods. The
      measurements were carried out with a hand-held optical probe that was manually
      scanned over the tumor-bearing breast. Increased blood flow was observed in tumor
      regions relative to healthy tissue, and control subjects did not exhibit
      significant blood flow heterogeneity. The measurements introduce a new optical
      contrast for diffuse optical mammography.

PMID- 16279470
TI  - Continuous-wave-controlled nonlinear x-wave generation.
AB  - We demonstrate that the interaction between a two-dimensional localized wave
      packet and a continuous-wave background can lead to efficient x-wave generation
      in nonlinear bidispersive optical systems. This x-wave generation process was
      found to depend on both the relative phase and amplitude of the background with
      respect to the superimposed wave packet. Pertinent configurations that lead to
      such generation are considered.

PMID- 16279471
TI  - Surface-emitted terahertz-wave difference-frequency generation in two-dimensional
      periodically poled lithium niobate.
AB  - We report on the demonstration of surface-emitted terahertz- (THz-) wave
      difference-frequency generation from two-dimensional (2D) periodically poled
      lithium niobate (PPLN). The two orthogonal periodic structures individually
      compensate for both the phase mismatch of the launched lasers and the generated
      THz wave. Tunable 1.5-1.8 THz wave generation with a bandwidth of 10-GHz was
      obtained by use of two 2D PPLN crystals. We also confirmed that THz waves were
      simultaneously generated into two opposite directions, which suggests the
      possibility of higher THz-wave output power.

PMID- 16279472
TI  - Application of the homogenization approximation to rough one-dimensional photonic
      crystals.
AB  - As previously reported [Opt. Lett. 29, 2791 (2004)], one-dimensional photonic
      crystals exhibit a decrease in their normal reflectivity if their interfaces are
      not flat. We show that the homogenization approximation accurately predicts this
      diminished optical response by comparing results with finite-difference time
      domain (FDTD) simulations applied to the same roughened structures. Within the
      parameter range tested (rms roughness < 20% and rms wavelengths < 100% of the
      photonic crystal periodicity), the homogenization approximation accurately
      reproduces the reflectivities obtained by the FDTD simulations, which are much
      more computationally expensive.

PMID- 16279473
TI  - Rotating vectorial vortices produced by space-variant subwavelength gratings.
AB  - A new class of vectorial vortex based on coherent addition of two orthogonal
      circularly polarized Bessel beams of identical order but with different
      propagation constants is presented. The transversely space-variant axially
      symmetric polarization distributions of these vectorial fields rotate as they
      propagate, while they maintain a propagation-invariant Bessel intensity
      distribution. These properties were demonstrated by use of discrete space-variant
      subwavelength gratings for 10.6 microm CO2 laser radiation. The polarization
      properties were verified by both full space-variant polarization analysis and
      measurements. Rotating intensity patterns are also demonstrated by transmitting
      the vectorial vortices through a linear polarizer.

PMID- 16279474
TI  - Large negative Goos-Hanchen shift from a weakly absorbing dielectric slab.
AB  - It is theoretically shown that the negative Goos-Hanchen shifts near resonance,
      Re[k(z)d] = m pi, can be an order of magnitude larger than the wavelength for
      both TE- and TM-polarized beams reflected from a weakly absorbing dielectric slab
      if the absorption of the slab is sufficiently weak, which is different from the
      case for a lossless dielectric slab [Phys. Rev. Lett. 91, 133903 (2003)].

PMID- 16279475
TI  - Synchronous self-elimination of autocorrelation interference in Fourier-domain
      optical coherence tomography.
AB  - We have developed a new algorithm and configuration for self-eliminating the
      autocorrelation of the object wave in Fourier-domain optical coherence
      tomography. A self-interferogram of the object wave is acquired synchronously
      with the standard interferogram of the recombined object and reference waves. The
      former is then subtracted from the latter after Fourier transformation. The
      algorithm is validated by numerical simulation and by experimental measurement of
      a U.S. Air Force target and a feline eye.

PMID- 16279476
TI  - Raman probe using a single hollow waveguide.
AB  - A simple Raman probe was realized using a single flexible hollow waveguide (HW).
      A HW coated with a silver film, which had reasonable transmission and little
      optical background noise, was used as a bidirectional transmission fiber for both
      the excitation and collection of Raman scattered light. The HW itself generated
      no Raman scattering or fluorescence noise during transmission. A complex
      filtering system at the end of the waveguide was thus unnecessary. In addition,
      the measured Raman spectra showed better signal-to-noise ratios than a
      conventional Raman fiber probe. The HW's suitability as a Raman fiber probe was
      also demonstrated.

PMID- 16279477
TI  - Resonant terahertz transmission in subwavelength metallic hole arrays of sub-skin
      depth thickness.
AB  - We study surface-plasmon-enhanced terahertz transmission through subwavelength
      metallic hole arrays of sub-skin-depth thickness. Dynamic evolution of surface
      plasmon resonance in terms of array thickness is characterized by use of
      terahertz time-domain spectroscopy in the frequency range 0.1-4.5 THz. A critical
      thickness of lead array film is observed, above which surface-plasmon coupling of
      terahertz pulses begins and is enhanced rapidly as the array thickness is
      increased toward the skin depth. The experimental results indicate that high
      efficiency extraordinary terahertz transmission can be achieved at an array
      thickness of only one third of skin depth.

PMID- 16279478
TI  - Mode-locked fiber laser frequency-controlled with an intracavity electro-optic
      modulator.
AB  - We demonstrate a mode-locked, erbium-doped fiber laser with its repetition
      frequency synchronized to a second fiber laser via an intracavity electro-optic
      modulator (EOM). With servo control from the EOM (bandwidth approximately 230
      kHz) and a slower speed intracavity piezoelectric transducer (resonance at
      approximately 20 kHz), we demonstrate stabilization of the repetition frequency
      with an in-loop rms timing jitter of 10 fs, integrated over a bandwidth from 1 Hz
      to 100 kHz. This represents what is to our knowledge the first time an EOM has
      been introduced inside a mode-locked laser cavity for fast servo action and the
      lowest timing jitter reported for a mode-locked fiber laser.

PMID- 16279479
TI  - Interexaminer reliability and validity for diagnosis of temporomandibular
      disorders of visual leg measurements used in dental kinesiology.
AB  - AIMS: To determine the reliability and the validity of visual leg measurements
      used in dental kinesiology, which suggests that a masticatory dysfunction, such
      as occurs in temporomandibular disorders (TMD), can influence the length and the
      internal rotation of lower limbs. METHODS: The leg-length inequality test and the
      internal foot-rotation test were performed independently by 3 different examiners
      on 41 subjects who were also screened for TMD. Data were analyzed by means of
      kappa statistics and by calculation of sensitivity and specificity values.
      RESULTS: Chance-corrected reliability was generally poor for both the leg-length
      inequality test (0.33 < or = k < or = 0.39) and the internal foot-rotation test
      (0.15 < or = k < or = 0.27). Sensitivity and specificity values of the tests to
      differentiate TMD and healthy subjects were below acceptable thresholds; they
      ranged from 0.41 to 0.57. CONCLUSION: Visual evaluations of leg-length inequality
      and internal foot rotation were unreliable and are not valid for TMD diagnoses.
      The results of chiropractic visual leg measurement procedures in dentistry should
      be interpreted with caution, particularly when clinical decisions may lead to
      nonreversible dental treatment.

PMID- 16279480
TI  - Catastrophizing is associated with clinical examination findings, activity
      interference, and health care use among patients with temporomandibular
      disorders.
AB  - AIMS: To examine whether catastrophizing is associated with clinical examination
      findings, pain-related activity interference, and health care use among patients
      with pain related to temporomandibular disorders (TMD). METHODS: Patients with
      TMD (n = 338; 87% female; mean age, 37 years) completed measures of pain, pain
      related activity interference, health care use, and depression, and received a
      Research Diagnostic Criteria/ Temporomandibular Disorders (RDC/TMD) clinical
      examination from an oral medicine specialist. RESULTS: Catastrophizing was not
      significantly associated with the more objective clinical examination measures of
      maximum assisted jaw opening and jaw-joint sounds, but it was associated with the
      more subjective examination measures (unassisted opening without pain, extraoral
      muscle site palpation pain severity, joint site palpation pain severity) and with
      increased TMD-related activity interference and number of health care visits (P
      values for all < .01). Even after controlling for demographic variables, pain
      duration, and depression severity, catastrophizing remained significantly
      associated with extraoral muscle and joint site palpation pain severity and with
      activity interference and number of health care visits. CONCLUSION: TMD patients
      who catastrophize have higher scores on clinical examination measures reflecting
      more widely dispersed and severe pain upon palpation of TMD-related facial muscle
      and joint sites, as well as greater TMD-related activity interference and health
      care use. Clinicians should consider screening patients with moderate or greater
      TMD pain and activity interference for catastrophizing. Cognitive-behavioral
      interventions may help reduce pain, disability, and health care use of patients
      who catastrophize.

PMID- 16279482
TI  - Post-traumatic stress disorder among patients with orofacial pain.
AB  - AIMS: To examine the presence and impact of post-traumatic stress disorder (PTSD)
      in a sample of patients seeking treatment for orofacial pain. METHODS: One
      hundred forty-one consecutive patients with an array of orofacial pain conditions
      were screened using a structured clinical interview for PTSD and the PTSD Symptom
      Checklist--Civilian Version (PCL), a brief PTSD self-report inventory.
      Additionally, participants received a clinical examination and self-report
      questionnaires to assess pain, coping styles, and presence of post-traumatic
      symptoms. RESULTS: Thirty-three (23%) patients received a full lifetime or
      current PTSD diagnosis, with an additional 11 patients receiving a partial PTSD
      diagnosis. Only 5 of these 44 patients had ever been previously diagnosed with
      PTSD. PTSD symptoms were associated with higher pain scores (P < .05) and
      affective distress (P < .01). Furthermore, discriminant function analyses
      suggested that the PCL accurately classified 89% of these cases (sensitivity =
      .85, specificity = .90, positive predictive power = 74%, negative predictive
      power = 95%). CONCLUSION: These results suggest that PTSD is prevalent in the
      orofacial pain setting and that PTSD symptomatology is associated with increased
      pain and affective distress that may complicate clinical presentation.
      Furthermore, PTSD can be accurately and efficiently assessed using a brief, self
      report inventory.

PMID- 16279481
TI  - Use of the Research Diagnostic Criteria for Temporomandibular Disorders for
      multinational research: translation efforts and reliability assessments in The
      Netherlands.
AB  - AIMS: To outline the steps taken to conduct and to culturally adapt Dutch
      translations of the Research Diagnostic Criteria for Temporomandibular Disorders
      (RDC/TMD) history questionnaire, clinical examination form, and verbal
      instructions to the patients, and to assess the reliability of the clinical
      examination. METHODS: For the linguistic translation from English into Dutch, the
      forward and back-translation approach was followed. For cultural adaptation, an
      expert panel reviewed the translation, and a pretest was performed on a small
      clinical sample. Examiner training and calibration were carried out, and the
      clinical reliability of a "gold standard examiner" and 3 clinicians was assessed
      on 18 symptomatic TMD patients and 6 asymptomatic controls. The order of the
      examinations was based on a quasi-random Latin square design. Intraclass
      correlation coefficients (ICCs) were calculated to assess the overall
      interexaminer reliability of the clinical examination. RESULTS: A linguistically
      valid and culturally equivalent translation of the RDC/TMD into Dutch resulted
      from the above-outlined procedure. As for the clinical reliability, the ICC
      values obtained could mostly be considered "excellent" or, less frequently, as
      "fair to good." Poor reliability was found only for some of the palpation tests.
      For uncommon diagnoses (disc displacement without reduction and without limited
      mouth opening; osteoarthritis), no reliable ICC value could be calculated.
      CONCLUSION: The mode described by the authors for preparing clinical sites for
      RDC/TMD-based research is a feasible one.

PMID- 16279483
TI  - Pressure pain threshold in the detection of masticatory myofascial pain: an
      algometer-based study.
AB  - AIMS: To compare pressure pain threshold (PPT) values for masticatory muscles in
      patients with signs and symptoms of myofascial pain and in asymptomatic
      individuals. METHODS: Fifty women with masticatory myofascial pain comprised the
      symptomatic group (group 1), while 49 TMD symptom-free women were selected as
      controls (group 2). The PPT was obtained with the aid of an algometer by applying
      pressure to the masseter and to the anterior, middle, and posterior temporalis. A
      90.8% specificity value was used to determine the appropriate PPT cutoff values
      for all 4 muscles studied. Receiver operator characteristic (ROC) curve areas and
      the likelihood ratio (LR) were also evaluated. RESULTS: The 3-way ANCOVA test
      (group, muscle, and side) revealed a significantly lower PPT for all muscles in
      the symptomatic group (P < .001). The lowest overall PPT was found for the
      masseter muscle, followed by the anterior, middle, and posterior temporalis (P <
      .001). The 90.8% specificity was obtained with PPT values of 1.5 kgf/cm2 for the
      masseter, 2.47 kgf/cm2 for the anterior temporalis, 2.75 kgf/cm2 for the middle
      temporalis, and 2.77 kgf/cm2 for the posterior temporalis. The anterior
      temporalis had the highest LR. ROC curve areas of 0.84, 0.92, 0.90, and 0.90 were
      obtained for the masseter, anterior, middle, and posterior temporalis,
      respectively. CONCLUSION: The masseter and temporalis muscles require different
      pressures for distinguishing masticatory myofascial pain patients from
      asymptomatic individuals. Because the highest sensitivity (77%) and LR were found
      for the anterior temporalis, this muscle was considered to have the most suitable
      discriminative capacity.

PMID- 16279484
TI  - Distribution of mucopolysaccharides and glycoproteins in the articular discs of
      temporomandibular joints in human fetuses.
AB  - AIMS: To evaluate the distribution of mucopolysaccharides and glycoproteins in
      the articular discs of temporomandibular joints (TMJs) in human fetuses at
      different stages of development in order to test the hypothesis that the
      development and histological maturation of the articular disc has already begun
      by the 12th week of gestation. METHODS: Eighteen human fetuses at gestational
      ages 12, 14, and 16 weeks were used (6 fetuses of each age). Sections (6 microm
      wide) of the articular discs were stained with trichromic stain for collagen
      fibers, Mayer's mucicarmine for mucopolysaccharides, and Schiff's periodic acid
      reaction for glycoproteins. The densities of the stained zones were measured by
      means of Image J software. The nonparametric Kruskal-Wallis test was used to
      evaluate the differences among stained zones in the 3 fetus groups. RESULTS: TMJ
      tissues of four of the six 12-week-old fetuses were stained positive for collagen
      fibers, mucopolysaccharides, and glycoproteins. In these fetuses the stain was
      localized to the articular posterior area and was denser in that area than in the
      middle and anterior areas. The stained areas in the 14-week-old fetuses were
      distributed throughout the articular discs, with isolated clear unstained areas.
      The stained areas of all the articular discs of the 16-week-old fetuses were more
      compact than those of the 12-and 14-week-old fetuses. In all the fetuses
      examined, the collagen fibers along the articular disc had a wavy appearance. The
      fossa of the temporal bone was observed in all the fetuses as a straight
      structure that was similar in the 3 fetus groups. The densities (mean +/- SD) of
      the stained zones were 38.36% +/- 3.39%, 59.5% +/- 1.56%, and 94.04% +/- 2.04%
      for 12, 14, and 16 weeks of gestation, respectively; these densities were
      significantly different (chi2 = 15.16; df = 2, P < .001). CONCLUSION: This study
      indicates that mucopolysaccharides and glycoproteins as well as collagen fibers
      are present at 12, 14, and 16 weeks of gestation. This suggests that the
      histological maturation of the articular disc has already begun at the 12th week
      and is complete by the 16th week of gestation.

PMID- 16279485
TI  - The effect of experimental cartilage damage and impairment and restoration of
      synovial lubrication on friction in the temporomandibular joint.
AB  - AIMS: To evaluate how the frictional coefficient of the porcine temporomandibular
      joint (TMJ) is affected by an impairment of the synovial lubrication produced by
      an experimental abrasion of the articular cartilage and the application of
      hyaluronic acid (HA) with different molecular weights to the abraded cartilage
      surfaces. METHODS: Erosion of the articular cartilage was produced by scouring it
      with sandpaper. Impairment and restoration of synovial lubrication were modeled
      by washing the joint space with phosphate-buffered saline (PBS) and by the
      application of HA with different molecular weights. After measuring the
      frictional coefficients in the intact TMJs (n = 10), the effects of washing with
      PBS, sandpaper scouring, and the application of HA were subsequently examined.
      RESULTS: The mean frictional coefficient in the intact joint was 0.0154 (SD
      0.0043). After PBS washing and sandpaper scouring, it increased significantly to
      0.0235 (SD 0.0052) and 0.0520 (SD 0.0088), respectively. Subsequent application
      of HA resulted in a significant decrease (43% to 56%) of the frictional
      coefficient. Observations by scanning electron microscopy showed that after
      sandpaper scouring, the superficial cartilage layer was disrupted and inner layer
      was exposed, creating an irregular surface. CONCLUSION: Joint friction may
      increase by approximately 350% following an experimental scouring of the
      cartilage surface and impairment of synovial lubrication. Lubrication by means of
      HA decreased joint friction by approximately 50%.

PMID- 16279486
TI  - Case report of a posterior disc displacement without and with reduction.
AB  - This article presents the case of a patient with an acute posterior disc
      displacement without reduction (PDDWR), whose temporomandibular joint (TMJ)
      showed, after physiotherapeutic manipulation, the characteristics of a posterior
      disc displacement with reduction (PDDR). Opto-electronic condylar movement
      recordings in both the PDDR state and the PDDWR state, and magnetic resonance
      imaging (MRI) scans of the TMJ in the PDDR state were carried out to document the
      case. The first 2 physiotherapeutic manipulations were initially successful in
      reducing the disc, but a few days later the joint showed a relapse to the PDDWR
      state. From the third manipulation on, now 12 months ago, the patient has been
      free of symptoms of the PDDWR state. Condylar movement traces of the joint in the
      PDDWR state indicated that the condyle was prevented from entering the fossa
      completely. The downward condylar movement deflections during the early phase of
      closing, recorded after the second manipulation, showed the reduction of the
      posteriorly displaced disc during closing. The movement recordings also showed
      that the PDDR could be eliminated by submaximal opening and closing movements.
      The MRI scans, taken after the third, successful manipulation, showed the disc to
      be in a normal position with respect to the condyle when the mouth was closed,
      and to be posteriorly displaced when the mouth was maximally opened. The case
      shows that manipulation techniques may successfully reverse an acute PDDWR into a
      PDDR. The technique of MRIs and condylar movement recordings show promise in
      further unraveling the morphological and clinical features of posterior disc
      displacements.

PMID- 16279487
TI  - International Association for the Study of Pain. 11th World Congress on Pain.
      August 21-26, 2005, Sydney, Australia.

PMID- 16279488
TI  - [Pathomorphology of the endocardium and myocardium in the heart injury].
AB  - Light, polarization, luminescent microscopy, phase contrast, special staining
      methods and scanning electron microscopy were used for studying sections and
      fragments of the endocardium and myocardium from 123 patients who had died of
      heart contusion and ischemic heart disease and from 50 rats with experimental
      heart contusion. The morphological classification of heart contusion and
      differential-diagnostic table of myocardial alterations due to contusion of the
      heart and ischemic heart disease are proposed to facilitate pathomorphological
      diagnosis of heart contusion. The classification of pathomorphological signs in
      heart contusion is presented.

PMID- 16279489
TI  - [Modern structure of the pancreatic injuries].
AB  - Current structure of pancreatic traumas of peace time is considered. The
      dynamics, mechanism and characteristics of pancreastic injury are described.
      Surgical treatment of pancreatic injuries and causes of their inadequate
      management are analysed. This will contribute to improvement of the quality of
      treatment of pancreatic injuries and of expert evaluation.

PMID- 16279490
TI  - [Estimation of postnatal life duration of the premature newborns by postnatal
      involution of hemopoietic tissue of the liver].
AB  - 140 dead fetuses and neonates of 21-40 week gestation were studied with
      morphometric study of hemopoietic activity of hepatic parenchyma. The correlation
      regression analysis has established that hemopoietic activity of the liver in
      premature neonates reduces exponentially with duration of their extrauterine
      life. First, there was hyperplasia of hemopoietic tissue of the liver, its
      involution was observed 19 hours after birth, on the average, reaching maximum to
      the end of early neonatal period. Basing on the difference of gestation age
      estimated by the degree of hemopoietic activity of hepatic parenchyma and
      neonatal mass, a regression model of determination of neonatal period of life of
      premature babies was developed. The results of the study can be used for
      practical application in forensic medical examination of perinatal death cases.

PMID- 16279491
TI  - [Forensic medical characteristics of the injuries inflicted by home-made
      arbalest].
AB  - The classification of arbalests as a representative of the class of missiles is
      presented. Basic design characteristics of such weapon, wounds and damage to
      cotton targets from shot distances 1, 3, 5, 10 and 15 m are described.

PMID- 16279492
TI  - [Estimation of shooting distance for a pneumatic gun MP-654 K loaded with small
      lead shots].
AB  - The experimental material has shown possibility of definition of shooting
      distance and some technical characteristics of the barrel of the pneumatic gun
      loaded with shots.

PMID- 16279493
TI  - [Forensic medical examination of abrasions in the study of mummified tissues in
      experiment].
AB  - Morphological and biophysical characteristics of abrasions and intact skin were
      studied during the process of their mummification at temperatures from 40 to 70
      degrees C. The time after which the injuries become undetectable because color of
      the skin and injuries coincides, was determined. Changes in configuration and
      area of abrasions while drying are described. The rate of mummification and
      duration of the latter were established by dielectric indices of abrasions and
      skin at 10 cm wave length.

PMID- 16279494
TI  - [Forensic-medical assessment of terroristic chemical attacks].
AB  - By potential damage, chemical terroristic attacks are much more dangerous than
      terroristic bombing. To fight chemical terrorism it is necessary to create the
      system of medical-environmental defense of the population. In line with emergency
      medicine, forensic medical service is a very important element of the
      antiterroristic defense. The activity of forensic-medical experts in the field of
      terroristic chemical attack is analysed.

PMID- 16279495
TI  - [Identification of human gender by hand x-ray].
AB  - A planimetric analysis of hand bones x-ray images is proposed for gender
      identification. The gender is determined by two methods: by interval estimation
      of bones size and calculation of the discriminant function and its comparison
      with group centroid values.

PMID- 16279496
TI  - [Personal identification by complex study of characteristics of the teeth and
      dentition structures].
AB  - A multimodality dental examination was made and anatomomorphological features of
      teeth and tooth sequences were studied in 200 policemen using clinical
      examination, morphological investigation of plaster jaw models, analysis of x
      rays and statistics, intraoral videocamera pictures, computer processing. The
      scheme of creation of dental data bank applicable in personal identification is
      offered.

PMID- 16279497
TI  - [Properties of the molecular-genetic individual identification system on the
      basis of D1S111 locus in terms of forensic-expert typing of DNA].
AB  - The article presents a comparative analysis of reference nucleotide sequences for
      locus D1S111, estimation of basic parameters of this locus polymorphism in the
      representative sample of Russian population for use as an individual
      identification molecular-genetic system in forensic expert examinations.

PMID- 16279498
TI  - [Use of thin-layer chromatography for detection of 11-nor-9-carboxy-delta9
      tetrahydrocannabinol in the urine].
AB  - A simple method of thin-layer chromatography for detection of 11-nor-9-carboxy
      delta9-tetrahydrocannabinol in biological material (urine) can be used in
      chemicotoxicological laboratories and chemical departments of forensic-medical
      expert examination without special facilities.

PMID- 16279499
TI  - [Detection of furadan in biological fluids].
AB  - Optimal conditions have been determined for furadan isolation from biological
      fluids by means of the mixture of solvents ethyl acetate-acetone in volume 1:1.
      Possible purification of the compound from coextractive substances of biomaterial
      on the column with silica gel L 100/160 mcm is demonstrated. IR
      spectrophotometric methods and high performace liquid chromatography with a
      detector of photodiode matrix are proposed for identification and quantitation of
      furadan in blood and urine specimens.

PMID- 16279500
TI  - [Forensic-medical diagnostic implication of morphine levels in the blood and
      urine].
AB  - Toxicological characteristics are presented for 198 cases of acute parenteral
      poisoning with morphine and heroin. The range of their metabolites concentration
      in the blood and urine encountered in practice are analysed. Principal causes of
      death due to opiate poisoning in inpatients are shown. Opiates toxicity was
      assessed by the method of logit-regression and dose-effect curves for analysis of
      probability of death depending on opiate metabolite concentration in blood and
      urine. Relations between probability of death and detection of morphine in
      biological media of the victims are considered. Morphine concentrations in the
      blood and urine undoubtedly indicating morphine poisoning are determined.

PMID- 16279501
TI  - [Establishment of remoteness of the soft tissues trauma by morphological
      methods].

PMID- 16279502
TI  - [Vishnevskii's spots. History of the discovery].

PMID- 16279503
TI  - Alternative therapies for postmenopausal women.
AB  - Alternative therapies are being used by postmenopausal women in attempts to treat
      all of the complaints and medical conditions of the menopause. One-fifth of those
      who take prescription drugs for these indications also take herbal remedies
      and/or high-dose vitamins, most often without disclosing the fact to the
      physician. Although studies of alternative therapies are short-term and rarely
      focused on safety--let alone efficacy--in the long-term, there are many studies
      spread over the large number of substances involved. More than 130 studies,
      including meta-analyses, are reviewed in this article under the headings of
      phytoestrogens, especially from soy; therapies for hot flushes; and preventives
      for cardiovascular disease, osteoporosis, and breast cancer. Special attention is
      given to the recently recognized daidzein metabolite equol, and for the sake of
      completeness there are reviews of the unconventional, but not botanical,
      treatments estriol, transdermal progesterone, and dehydroepiandrosterone. The
      total picture produced by conscientious review of the studies is bleak overall,
      but there seems to be good reason to pursue the possibilities inherent in soy
      protein with phytoestrogens in populations of women who endogenously produce
      equol.

PMID- 16279504
TI  - Defining poor responders in assisted reproduction.
AB  - OBJECTIVE: The aim of this study was to establish an objective definition of
      "poor responders" for patients undergoing treatment with assisted reproduction.
      METHODS: A total of 782 infertile couples treated with assisted reproduction were
      studied by retrospective analysis of the data. Simple linear regression was
      performed between the number of oocytes retrieved and the clinical pregnancy
      rate. The sensitivity and specificity were then calculated and the receiver
      operator characteristic (ROC) curves were drawn in order to determine a critical
      number of oocytes retrieved below which the clinical pregnancy rate was
      significantly diminished. RESULTS: An excellent correlation was found between the
      number of oocytes retrieved and the clinical pregnancy rate (r = 0.90). The
      clinical pregnancy rate started to become significantly lower when fewer than 5,
      6, and 8 oocytes were retrieved from patients treated with ICSI, IVF, or
      TeSE/ICSI, respectively. CONCLUSIONS: The definition of poor responders in
      assisted reproduction depends on the treatment modality. Poor responders are
      patients undergoing treatment with ICSI, IVF, or TeSE/ICSI from whom fewer than
      5, 6, or 8 oocytes are retrieved, respectively.

PMID- 16279506
TI  - The journey from infertility to parenting multiples: a dream come true?
AB  - Infertility deeply affects psychosocial aspects of young couples, who often
      erroneously take fertility for granted. The inevitable transformation from
      apparently healthy adults into patients can lead to loss of self-esteem,
      confidence, health, close relationships, security, and hope. Frequently, when
      emotional and psychological resources are diminished after prolonged infertility,
      the couple may express their desperate wish for a family in the form of accepting
      without reservation the risks of a multiple pregnancy, ignoring the undeniable
      increased morbidity and mortality associated with these gestations. It is unclear
      why a couple embarking on the journey of infertility treatment may prefer a
      pregnancy that is tenfold as likely to have a serious adverse outcome. Of the
      three potential explanations for such an attitude--desperation, denial, and
      ignorance--only the last one can be solved with patient education and adequate
      counseling. At the same time, it is unjustified to avoid assisted reproductive
      technologies because of potential adverse outcome, however necessary it is to
      acknowledge the risk of multiple births.

PMID- 16279505
TI  - Gender gap in cerebrovascular accidents: comparison of the extent, severity, and
      risk factors in men and women aged 45-65.
AB  - BACKGROUND AND OBJECTIVE: Few data are available on sex differences among
      relatively young adult stroke patients. The aim of the present study is to
      analyze such differences in mortality, principal risk factors, and outcome
      measures among patients aged 45-65 with acute stroke. The identification of these
      differences is indispensable for developing optimal strategies for the prevention
      and care of this disease. METHODS AND RESULTS: Retrospective study of 114 women
      and 190 men, aged 45-65 years, hospitalized from 1990 to 1998 in the Hadassah
      Medical Centers with confirmed CVA. Medical background, clinical presentation,
      imaging results, risk factors, lifestyle information, and rehabilitative status
      data were retrieved from medical records. No gender differences were observed in
      clinical presentation or imaging studies. In-hospital mortality rate among women
      was higher than men, 13.2% vs. 5.8%. A significant gender gap in comorbidity with
      diabetes, hypertension, and hypercholesterolemia was found: 29.1% of women vs.
      14.3% of men. Men more than women had a history of ischemic heart disease (35.8%
      vs. 21.9%) and smoking and alcohol consumption (43.9% vs. 16.4%; 6.9% vs. 0.9%).
      Use of rehabilitative services was similar between the sexes. CONCLUSIONS: This
      study shows marked gender differences among younger adult stroke patients. The
      concomitance of multiple risk factors in the women may have contributed to the
      observed higher mortality rate. Characterization of risk factors for CVA in both
      sexes may aid in developing prevention strategies to reduce stroke incidence in
      this age group.

PMID- 16279507
TI  - The value of saline salpingosonography as a surrogate test of tubal patency in
      low-resource settings.
AB  - BACKGROUND: Tubal factor, which accounts for 15-30% of infertility in all women,
      is common in developing countries with high rates of pelvic inflammatory disease
      but limited resources. It is possible to outline the fallopian tubes by injecting
      isotonic saline transcervically during transvaginal ultrasound scanning of the
      pelvis, and both color flow Doppler and 3-dimensional scanning modes have been
      employed to improve visualization of the tubes, with varying success. METHOD: We
      investigated the value of saline salpingosonography (SSG), using 2-dimensional
      transvaginal ultrasound scanning, as a screening test of tubal patency in 113
      women by comparing SSG findings to those at HSG or laparoscopy. RESULTS: The
      findings at SSG correlated well with the results of HSG or laparoscopy, with an
      overall concordance of 82.5%. SSG was more accurate at diagnosing patent tubes
      than blocked tubes and was well tolerated. The results are, however, unreliable
      when it is difficult to inject the saline and when the patient experiences severe
      pain during the procedure. CONCLUSION: SSG is a useful screening tool for
      investigating infertility, particularly in low-resource settings.

PMID- 16279509
TI  - [Pneumonias: diagnosis and antibacterial therapy].

PMID- 16279508
TI  - Introital swab testing for Chlamydia trachomatis in a resource-poor setting: an
      Indian perspective.
AB  - OBJECTIVE: Chlamydia trachomatis (CT) is implicated both in tubal infertility and
      in cervical dysplasia. Early detection of this infection is uncommon due to its
      asymptomatic nature and to lack of adequate health care facilities, leading to
      irreversible sequelae. This study evaluates the use of an introital specimen from
      women attending the Institute's infertility clinic to detect CT by polymerase
      chain reaction (PCR) and to correlate it with intraepithelial changes (IEC) of
      the cervix by Pap smears. METHODS: Introital and endocervical swab specimens were
      taken from 100 infertile women for PCR. An endocervical smear was taken for Pap
      staining. RESULTS: The CT infection rate was 34%. Sensitivity of introital and
      endocervical specimens for detection of CT was 82.4% and 85.3%, respectively (P >
      0.05); both had 100% specificity. Sixty-seven percent of infected women were less
      than 30 years of age and only 15% of these reported discharge.
      Vaginitis/cervicitis was observed in 35% of the positive cases. IEC suggesting
      inflammation was seen in 74% of the infected women, as compared to 48% of
      subjects with normal cytology (p = 0.016). Being noninvasive, self collection of
      an introital specimen can be advocated in large-scale settings in our country for
      detection of CT in order to contain the infection and its complications.

PMID- 16279510
TI  - [Activated oxygen metabolites in tuberculosis].

PMID- 16279511
TI  - [The tuberculosis epidemic situation and basic tuberculosis-controlling measures
      in Moscow in 1934-2003].

PMID- 16279512
TI  - [Primary respiratory tuberculosis in children: Hyperdiagnosis or hypodiagnosis].
AB  - The diagnosis of bacteriologically negative tuberculosis (TB) in children is
      traditionally based on clinical criteria, such as a history of contact with a
      patient with TB, a positive tuberculin test suggesting TB infection and
      radiological TB changes. To improve the early diagnosis of TB, the authors
      applied computed tomography (CT) to 284 children with suspected TB (a study
      group) who had negative bacterial tests and normal chest X-ray films. To identify
      individual diagnostic criteria, the study group was divided into 4 subgroups: 1)
      119 patients with positive tuberculin tests (> or = 10 mm induration) and a known
      contact with a TB patient; 2) 100 patients with positive tuberculin tests (> or =
      10 mm induration) without known contact with a TB patient; 3) 33 patients with
      negative tuberculin tests (> or = 10 mm induration) and a known contact with a TB
      patient; 4) 32 patients with negative tuberculin tests (> or = 10 mm induration)
      without known contact with a TB patient. A control comprised 29 children with
      bacteriologically verified TB and normal chest X-ray films. Conventionally
      radiological studies revealed undiagnosed lung parenchymal abnormalities in 35
      (29.4%), 16 (16.0%), 4 (12.1%), and 5 (15.6%) children in Subgroups 1, 2, 3, and
      4, respectively, and in 11 (37.9%) children in the control group. Intrathoracic
      lymph nodes of > or = 5 mm were rarely diagnosed in all the groups of patients,
      including children with bacteriologically verified TB. Calcified lymph nodes were
      visualized in 62 (52.1%), 40 (40.0%), 18 (54.5%), and 7 (21.9%) children in
      Subgroups 1, 2, 3, and 4, respectively, and in 15 (51.7%) children in the control
      group. CT revealed an active TB process in 49 (41.2%), 23 (23.0%), 12 (35.4%) and
      1 (3.1%) children in Subgroups 1, 2, 3, and 4, respectively. The findings
      demonstrated the hypodiagnosis of active TB in the infected children contacting a
      TB patient when CT is not applied.

PMID- 16279513
TI  - [Influence of environmental factors on the immunological responsiveness of
      Mycobacterium tuberculosis-infected children].
AB  - The specific features of immunological responsiveness were studied in 124
      Mycobacterium tuberculosis (MBT)-infected children aged 7-14 years in relation to
      the ecological characteristics of their living area. All the children had early
      primary tuberculosis infection. The MBT-infected children were found to have
      first-degree secondary immunodeficiency. The latter was most pronounced in the
      dwellers of industrial areas, who had T-lymphocytic deficiency, the impaired
      supopulational composition of T cells, their diminished functional activity, an
      increased response to specific antigen, as well as dysimmunoglobulinemia,
      elevated levels of circulating immune complexes. The hyposuppressor types of
      cellular immunodeficiency and total T lymphopenia were observed in children
      living in the ecological crisis area. Superinfection and concomitant diseases
      create conditions for the progression of secondary immunodeficiency and for the
      development of severe forms of the disease.

PMID- 16279514
TI  - [Causes of death from tuberculosis in children under the present-day conditions].
AB  - Analysis of the causes of death from tuberculosis in 15 children in one of the
      central regions of Russia has indicated that in the past 14 years, the
      territorial childhood mortality rates have been 0.10-0.20 per 100,000 children.
      The main cause of death is tuberculous meningoencephalitis (n = 10); caseous
      pneumonia (n = 3), and generalized tuberculosis with severe concomitant diseases
      (n = 2) were less common. Tuberculous meningoencephalitis was postmortally
      diagnosed in 4 children who had received intensive nonspecific therapy using
      large doses of corticosteroid hormones. This led to the development of severe
      pyonecrotic meningoencephalitis with great brain edema and hemorrhoidal portions,
      which was early known as steroid-induced tuberculosis.

PMID- 16279515
TI  - [A new approach to treating secondary pulmonary hypertension].
AB  - OBJECTIVE: to study the clinical and hemodynamic effects and safety of the ACE
      inhibitor dirotone and AT1-receptor antagonist losartan in secondary pulmonary
      hypertension (PH) in patients with chronic obstructive bronchitis (COB). SUBJECTS
      AND METHODS: The time course of changes in hemodynamic parameters and diurnal BP
      profile in 48 patients with COB concurrent with Functional Class (FC) III-IV
      secondary PH, receiving 4-week therapy including dirotone and losartan. RESULTS:
      The inclusion of dirotone or losartan into the combined therapy of patients with
      secondary pulmonary hypertension resulted in alleviated PH, caused positive
      changes in the right cardiac cavities, and normalized diurnal BP variables.
      Therapy with dirotone was effective in COB patients with the clinical signs of FC
      III PH only during its course use, that with losartan was beneficial in FC III
      and IV PH. The long-term outpatient use of losartan in individually adjusted
      doses produced pronounced beneficial clinical effects and led to significantly
      improved hemodynamic parameters. CONCLUSION: The ACE inhibitor dirotone and the
      AT1-receptor antagonist losartan may be recommended for the correction of
      hemodynamic disorders in secondary PH in patients with COB.

PMID- 16279516
TI  - [Intensive pharmacotherapy for massive recurrent pulmonary hemorrhages].

PMID- 16279517
TI  - [Impact of drug resistance of the causative agent on the outcomes of treatment
      for pulmonary tuberculosis in the Arkhangelsk Region].
AB  - The present study was undertaken to assess the results of treatment in patients
      with pulmonary tuberculosis in the Arkhangelsk Region in 1999 and to analyze the
      results of treatment in relation to the infection with Mycobacterium tuberculosis
      with different profiles of sensitivity to antituberculous drugs. The outcomes of
      treatment were assessed in relation to the infection with Mycobacterium
      tuberculosis with different profiles of sensitivity to antituberculous drugs in
      76 patients to whom the BACTEC test was applied. Beneficial effects of therapy
      were recorded in 150 (63.9%) of the 235 new cases. In 29 (12.3%) patients, it
      ended in death, ineffective treatment was recorded in 20 (8.5%) first detected
      patients; 29 (12.3%) new cases discontinued treatment; the result of therapy was
      unknown in 7 (3.0%). There was a low efficiency of chemotherapy (26.2%), its
      inefficiency in 24 (39.4%) patients; treatment was discontinued in 18 (29.5%)
      cases and its outcome was unknown in 1 (1.6%) patient. Resistance to one
      antituberculous agent timely used in the effective chemotherapy regimen did not
      affect the outcome of treatment. The spread of drug resistance in pulmonary
      tuberculosis in the Arkhagelsk Region directly affects the outcome of the
      disease.

PMID- 16279519
TI  - [Postoperative rehabilitation in patients with sequels of tuberculous and
      nonspecific gonitis after total endoprosthetic repair of the knee joint].
AB  - To evaluate the effectiveness of rehabilitative measures, comprehensive studies
      have been conducted in 37 patients with sequels of tuberculous and nonspecific
      gonitis, who underwent primary total endoprosthetic repair of the knee joint with
      an Osteonics-7000 cement fixation prosthesis (USA) in 1996 to 2002. After
      discharge from hospital, 18 patients received a complete course of
      rehabilitation, 19 patients refused it for different reasons. The results were
      assessed just after completion of the course of rehabilitation (3 months after
      surgery), following 1 year and on the last examination (on the average 45.2
      months later). Statistically significant advantages in the function of the knee
      joint and in the force of its extensors were observed in the group of patients
      undergoing a complete course of postoperative rehabilitation just after
      completion of the course and a year after surgery. The last examination revealed
      a great difference between the patients who had undergone a complete course of
      rehabilitation and those who had refused it.

PMID- 16279518
TI  - [The predictive value of thyroid function in patients with respiratory
      tuberculosis].
AB  - Enzyme immunoassay was used to determine the levels of thyrotropric hormone
      (TTH), total and free fractions of thyroxine, and triiodothyronine in patients
      with respiratory tuberculosis. 61.8% of the patients were found to have type 3
      euthyroid pathology that was characterized by the elevated levels of thyroxine
      and triiodothyronine with the unchanged level of TTH and by the absence of
      clinical manifestations of thyrotoxicosis. The levels of the total and free
      fractions of triiodothyronine and thyroxine were higher in patients with lung
      destruction, dissemination, or bacterial isolation than in those without these
      manifestations. The positive clinical and X-ray changes were followed up by
      regression of thyroid shifts in patients with the baseline high values of thyroid
      hormones. Antituberculous drugs did not affect thyroid function.

PMID- 16279520
TI  - [Geography of endobronchial pathology in the Astrakhan Region during
      anthropogenic burden of the region].
AB  - Bronchoscopy was made in 2264 patients with tuberculosis (1998-2003). The
      development included 1274 patients with endobronchial pathology that was divided
      into 3 groups: 1) nonspecific endoronchitis; 2) tuberculous bronchial lesions (+
      cicatricial stenoses); and 3) benign and malignant bronchial tumors. In the
      Astrakhan Region, endobronchial pathology is nonuniformly distributed, its
      greater proportion being observed in the southeastern and south-western areas of
      the region. Endoronchitis holds the lead (74%), next are bronchial tuberculosis
      (19%) and tumors (7%). There is an association of endobronchial pathology with
      atmospheric discharges of noxious substances exceeding the maximally allowable
      concentrations. Moreover, a correlation analysis revealed a close relationship of
      endobronchitis to bronchial tuberculosis and a tumorous process.

PMID- 16279521
TI  - [A case of tuberculosis of the appendix vermiformis].

PMID- 16279522
TI  - [A case of misdiagnosis of tuberculosis in a patient with pulmonary
      lymphogranulomatosis and destructive pneumonia in the presence of AIDS].

PMID- 16279523
TI  - [The Ryazan regional pediatric tuberculosis sanatorium].

PMID- 16279524
TI  - [Isolation rate of enterotoxigenic staphylococci in patients with sepsis,
      pneumonia and burns].
AB  - The occurrence of Staphylococcus aureus strains producing enterotoxins of types
      SEA and SEB, which isolated from patients of different profile and caused the
      infectious process accompanied by pronounced intoxication without vomiting and
      enteric disturbances, was determined by means of the indirect hemagglutination
      test. The collection included 28 strains isolated in sepsis, 38 strains isolated
      in pneumonia, 57 strains isolated from patients with burns and 23, from the hands
      and nasopharynx of the medical staff. Among the staphylococcal strains isolated
      in sepsis, 75.6% synthesized SEA and 5.4%, SEB. The occurrence of SEA- and SEB
      positive strains isolated in pneumonia was, respectively, 42.1% and 2.6%. From
      patients with burns SEA-positive staphylococci were mainly isolated (92.9%). Only
      3% of the cultures isolated in wound infections produced SEA. From the medical
      staff, 13.4% of SEA-positive strains and 17.3% of SEB-positive strains were
      isolated. The data obtained from this study indicate the expediency of the
      determination of the enterotoxigenic properties of S. aureus clinical isolates in
      medical institutions for prophylactic measures with a view to the prevention of
      the spread of pathogenic clones.

PMID- 16279525
TI  - [Influence of glucose and galactose on the morphology and biological properties
      of Yersinia pseudotuberculosis].
AB  - When cultivated in the presence of glucose, irrespective of temperature and the
      degree of aeration, Y. pseudotuberculosis cells have the ovoid form, constant
      size and low hydrophobic properties of their surface. Meanwhile the
      characteristics of the bacteria grown in the medium, carbohydrate-free or with
      galactose added, essentially depend on the conditions of medium aeration. Under
      the conditions of intensive stirring at both temperatures these bacteria acquire
      the coccoid form, not typical for Yersinia, they have a smaller area
      (approximately 2 times) and more hydrophobic surface in comparison with the cells
      grown in the presence of glucose. Under stationary conditions the differences
      between the cells, cultivated in the presence of galactose and glucose, in form
      and area disappear, but the differences in the hydrophobic properties of the
      surface are retained. As revealed in this study, the cells grown in the presence
      of galactose and under the conditions of intensive medium stirring, in contrast
      to those grown with glucose, have 1.5-fold greater invasive activity,
      irrespective of aeration conditions, eightfold greater resistance to ampicillin
      and twofold greater resistance to streptomycin and erythromycin.

PMID- 16279526
TI  - [Profiles of the utilization of 20 amino acids as the only source of nitrogen and
      carbon in bacteria of the genera Klebsiella, Enterobacter, Serratia,
      Escherichia].
AB  - The profiles of the utilization of 20 protein amino acids in 118 Klebsiella
      pneumoniae sub- sp. pneumoniae, K. oxytoca, K. planticola, K. mobilis,
      Enterobacter cloacae, Serratia marscescens, S. liquefaciens, Escherichia coli
      strains isolated from clinical material were studied. The utilization of amino
      acids was determined on minimal saline agar containing amino acid as the only
      source of nitrogen and carbon; the results were evaluated after 72-hour
      incubation at 37 degrees C. 17 profiles of amino-acid utilization were thus
      determined, most of them genus-specific in enterobacteria: Klebsiella (profiles
      No. 1--6, 9, 10), Enterobacter (No. 11--13), Serratia (No. 14--16), Escherichia
      (No. 17). The full coincidence of amino-acid utilization profiles in bacteria of
      K. mobilis (No. 1, 6) and K. pneumoniae subsp. pneumoniae with out of such
      profiles in bacteria of the genera Enterobacter, Serratia, Escherichia was
      established, which confirmed that K. mobilis (formerly Enterobacter aerogenes)
      belonged to the genus Klebsiella.

PMID- 16279527
TI  - [Level of IgG antibodies to bacteria of 12 species in the blood sera of rabbits,
      immunized with preparations obtained from Neisseria meningitidis, grown under the
      stress conditions].
AB  - The blood sera of rabbits, immunized with preparations obtained from N.
      meningitidis of serogroups A, B or C, cultivated under the stress conditions,
      were studied. These sera were found to contain IgG antibodies not only to N.
      meningitidis antigens, but also to the bacterial antigens of 12 species. The sera
      of rabbits, immunized with meningococcal preparation of serogroup A, were found
      to have the elevated levels of IgG antibodies, in comparison with the control, to
      the antigens of 3 other bacterial species; the blood sera of rabbits, immunized
      with meningococcal preparation of serogroup B, were found the elevated levels of
      IgG antibodies to the antigens of 11 other bacterial species; and the blood sera
      of rabbits, immunized with meningococcal preparation of serogroup C, to the
      antigens of 9 other bacterial species. The study of serogroup B meningococci,
      used as an example, revealed the influence of the growth phase of the culture on
      the content of cross-reacting antigens. Their greatest amount was determined at
      the stationary phase when the stressor effect on the culture reached its maximum
      and their least amount, at the exponential phase when the stressor effect on the
      culture was minimal. It was, therefore, found to be expedient to obtain
      immunodiagnostic and test systems from N. meningitidis cultures, grown to middle
      of the exponential phase of growth.

PMID- 16279528
TI  - [Ultrastructural immunochemical study of pathogenic Burkholderia capsule].
AB  - The capsular structures of Burkholderia pseudomallei, B. mallei, B. cepacia and
      their avirulent noncapsular mutants were studied with the use of electron ahd
      immunocytochemical techniques. For this purpose, antimelio-idosis monoclonal
      antibodies (McAb) G11 and 1 G2, epitope-aimed at capsular glycopyotein of 200 kD
      and outer-membrane proteins of 42 and 39 kD, were used. As revealed in this
      study, the typical causative agents of melioidosis and glanders formed the
      capsule and exhibited high virulence due to the antiphagocytic activity of 200 kD
      glycoprotein, whose epitopes were found to be incorporated into the capsule, in
      contrast to avirulent variants and B. cepacia, found to have no such structure.
      The recognition of the membrane determinants of McAb 1 G2 on the outer-membrane
      surface of the non-capsular variants of microbes known to be the causative agents
      of melioidosis and glanders was indicative of absence of the capsule in these
      microbial cells. These data concerning the role of 200 kD antigen in virulence,
      its structural and functional characteristics may be efffectively used in the
      study of the pathogenetic mechanisms of melioidosis and glanders, as well as in
      the construction of preparations for their immunodiagnostics and prophylaxis.

PMID- 16279529
TI  - [The effectiveness of antibiotics on bacteria in biofilms].
AB  - Bacteria can form different types of communities, united by common notion:
      biofilms. The aim of the present study was to determine the capacity of different
      antibiotics to penetrate into biofilms and act on unrelated bacteria. The study
      revealed that the formation of barriers between the community and the environment
      on artificial biofilms occurred in all strains of unrelated Gram-positive and
      Gram-negative bacteria used in this investigation. The capacity of antibiotics to
      penetrate into biofilms varied in different strains of the same species. For
      certain antibiotics similarity in their penetrating capacity was found to exist
      with respect to biofilms of unrelated bacteria. The penetration of antibiotics
      into mixed biofilms depended on the strain which determined its minimal value, so
      that the protection of one microorganism by another was thus observed. The method
      for the evaluation of the effectiveness of antibiotic penetration into bacterial
      biofilms, suitable for use in bacteriological laboratories, is proposed.

PMID- 16279530
TI  - [The ecology and prevalence of arboviruses on the territory of the Saratov
      Region].
AB  - The territorial spread of Tahyna, Batai, Sindbis, West Nile fever and Crimean
      Congo hemorrhagic fever viruses throughout the Saratov region in 1998 - 2000 was
      analyzed. The characteristics of the epizootic activity of the natural foci of
      these arboviruses in different landscape zones (temperate forest-steppes, steppes
      and semi-deserts) were calculated. The species composition of small mammals, the
      natural reservoirs of the causative agents of arbovirus infections, was
      determined.

PMID- 16279531
TI  - [Ensuring the sanitary and epidemiological safety of the child population in
      Russia].
AB  - The summarizing data on new negative tendencies in the state of health of
      children and adolescents in Russia are presented. The two-fold increased
      proportion of children with chronic pathology and disability is noted. Special
      attention is drawn to a high level of child morbidity in diseases of respiratory
      organs, especially bronchial asthma. Measures ensuring the sanitary and hygienic
      safety of the child population in Russia, including improvements in the
      organization of nourishment, vaccinal prophylaxis, working out hygienic criteria
      and health-saving technologies, have been analyzed. Priorities in the work aimed
      at the liquidation of negative tendencies in the health of the child population
      in Russia have been determined.

PMID- 16279532
TI  - [Epidemic process of pertussis in Moscow].
AB  - Materials reflecting the dynamics of pertussis morbidity during the period of
      1958 - 2003 under the conditions of prolonged mass immunization of the child
      population with adsorbed DPT vaccine are presented. The planned vaccination of
      children led to the decrease of pertussis morbidity during the first 10 years,
      but groundless abstentions from vaccination during the 1980s - 1990s contributed
      to a sharp rise in morbidity among children of younger age groups. During the
      recent four years a rise in pertussis morbidity was registered in 2000 (71.79 per
      100,000 of the population), followed by the most significant for the last 20
      years drop in morbidity in 2002--down to 9.89. But in 2003 the growth of
      morbidity was again registered (38.67). Recently periodic rises and drops in
      morbidity occurred simultaneously with the increased coverage of children of
      younger age groups with vaccination. In recent years changes in the age structure
      of patients were observed: the specific proportion of school children increased
      (in 2003 morbidity rates in children aged 6 - 10 years were 288.6 - 270.7),
      simultaneously high morbidity among children aged up to one year (274.9) was
      registered. The specific proportion of pertussis-affected children aged above 7
      years reached 65%. From the late 1990s until present in 87.1% of cases strains of
      serotype 1.0.3 prevailed in the population of B. pertussis strains. But in recent
      years the circulation of strains 1.2.3, spread in the prevaccination period and
      having toxicity similar to that of strains of serotype 1.0.3, while exceeding
      them in virulence, in sufficiently high proportion (7.0% in 2002) was noted. This
      was indicative of the possibility of the unfavorable development of the epidemic
      process of pertussis infection.

PMID- 16279533
TI  - [Evaluation of the vaccinal process in skin-scarification and oral immunization
      of rabbits with live smallpox vaccines].
AB  - On the basis of comparative experimental evaluation of specific features in the
      course of the vaccinal process after the immunization of laboratory animals with
      live smallpox vaccines, intended for oral use (in tablets) and for skin
      scarification was proposed. In experiments on rabbits, made with the use of
      virological and immunological methods, the counteraction of the elements
      constituting the vaccinal process was analyzed, the integral evaluation of its
      course was given, the greater safety of the oral preparation in comparison with
      the traditional vaccine for immunization by skin-scarification method were
      established. The conclusion was made that oral immunization was the safest
      immunization method under modern conditions and promising one for using live
      vaccines with population immunity being at a low level or absent.

PMID- 16279534
TI  - [Immunological characteristics in the therapy of atopic dermatitis in children
      with polycomponent vaccine Immunovac BN-4].
AB  - IgE-mediated reactions linked with the polarization of the immune process
      towards, mainly, the activation of Th2 lymphocytes which synthesized
      interleukins, responsible for switching over B lymphocytes to the production of
      IgE, were found to be the most important mechanism of the pathogenesis of atopic
      dermatitis (AD). The use of immunomodulating preparations, capable of changing
      unbalance in the system of Th1/Th2 cells, is one of promising approaches to the
      complex therapy of AD. Poly-component vaccine Immunovac BN-4 was included into
      the complex therapy of AD in children, The dynamics of immunological
      characteristics was studied for the period of 6 months after the end of the
      course of therapy. A considerable increase in the absolute and relative amount of
      lymphocytes with markers CD3, CD4, CD16, CD21, CD25, a rise in the levels of IgA,
      IgG and a decrease in the level of total IgE in the blood serum were established.
      The inclusion of the polycomponent vaccine into the complex therapy of AD may be
      recommended.

PMID- 16279535
TI  - [Preparation of Pseudomonas aeruginosa recombinant outer-membrane protein F and
      the study of its antigenic properties].
AB  - In Escherichia coli M15, the gene of P. aeruginosa recombinant outer-membrane
      protein F (OprF) was cloned. OprF, chromatographically purified on Ni-agarose and
      containing an additional sequence of 6 histidines on the N-end, was obtained. The
      purified OprF specifically reacted with rabbit serum, hyperimmune to P.
      aeruginosa, and in the mice injected with this protein specific IgG antibodies
      were synthesized. The optimum concentrations of P. aeruginosa OprF were selected
      for further tests of its protective properties from infection induced by P.
      aeruginosa.

PMID- 16279536
TI  - [Antibacterial acitivity of the peptide complex isolated from the preparation of
      leukocytic interferon].
AB  - A complex of low-molecular cationic peptides having an anti-bacterial effect with
      respect to Gram-positive and Gram-negative bacteria was isolated from the
      preparation of leukocytic interferon. The antibacterial action of the peptide
      complex was experimentally studied in vitro. The study revealed that the degree
      of the antibacterial activity of the peptide complex depended on the
      concentration of the bacterial culture under study, the ionic power of the
      incubation medium and did not depend on the presence of the products of bacterial
      vital activity in the growth medium. The antibacterial action of the peptide
      complex on the test cultures of Gram-positive and Gram-negative bacteria, as well
      as on the cultures of bacteria isolated from patients with infectious
      inflammatory diseases of the organs of the urinary system, was established. These
      results opened prospects for the development of fundamentally new antibacterial
      preparation on the basis of the peptide complex obtained in our studies.

PMID- 16279537
TI  - [Generation of dendrite cells and the use of immunomodulators of bacterial origin
      as cell differentiation inducers].
AB  - The generation of ripe dendrite cells (DC) of marrow origin was obtained with the
      use of the vaccine Immunovac-BN-4, an immunomodulator of microbial origin, as
      well as Klebsiella pneumoniae LPS and TNF-alpha, as ripening inducers. These
      inducers equally led to the ripening of DC. The generation of ripe DC was
      characterized by morphological, phenotypical and functional changes. The
      immunophenotype of cells altered from CD34+, CD38-, CD40-, CD80-, CD86-, MHC I-,
      MHC II-, F4/80- to CD34-, CD38+, CD40+, CD80+, MHC I+, MHC II+, F4/ 80(low). In
      parallel with the ripening of DC their phagocytic activity decreased. In culture
      medium with ripe DC the levels of such cytokines as IL-1b, IL-6, IL-12, IFN
      gamma, TNF-alpha significantly increased and the production of IL-4 decreased.
      The content of IL-2 and IL-10 remained unchanged.

PMID- 16279538
TI  - [Electrophoretic mobility and energy charge of the adenyl system of blood
      lymphocytes in guinea pigs immunized against plague with strain Yersinia pestis
      ev subcultures with different immunogenicity].
AB  - The injection of highly immunogenic vaccine strain Yersinia pestis EV, line
      NIIEG, into guinea pigs was accompanied, as early as 24 hours after this
      injection, by a drop in the electrophoretic mobility of the main amount of
      lymphocytes, significant shifts in the content and quantitative relation of
      adenine nucleotides in the mixed lymphocyte population, as well as T and B
      lymphocytes after their preparative electrophoretic sorting. The immunizatiom of
      guinea pigs with strain EV of the Japanese line, possessing faint immunogenic
      properties, produced few changes in the electrophoretic mobility of lymphocytes;
      no significant changes in the energy charge of the adenylate system of
      lymphocytes and their subpopulations in comparison with intact animals were
      established. The study of the metabolic processes in lymphocytes and their
      populations makes it possible to give more precise characterization to evaluate
      the prospects of various vaccine preparations.

PMID- 16279539
TI  - [Antibiotic resistance and putative origin of Staphylococcus aureus and
      Klebsiella strains isolated from the children with intestinal dysbacteriosis].
AB  - The results of the statistical treatment of data on the analyses of 766 children,
      the residents of Moscow, for dysbacteriosis are presented; of these children, 34
      were aged up to 1 month and 732, from 1 month to 1 year. This study revealed that
      in the fist year of life in children with dysbacteriosis the dominating bacterial
      species were S. aureus, bacteria of the genus Klebsiella and fungi of the genus
      Candida. From the intestine of children aged up to 1 month S. aureus and
      Klebsiella were isolated more often than from children aged up to 1 year. The
      results of the study of antibioticograms demonstrated that 21.6% of S. aureus
      strains and 74.4% of Klebsiella strains were multiresistant to antibiotics.
      Taking into account the fact that multiresistance to antibiotics was
      characteristic of hospital strains, the suggestion was made that the isolated
      strains were of hospital origin and such strains could colonize the intestine of
      children in maternity hospitals.

PMID- 16279540
TI  - [The verification of the results of screening antibodies to hepatitis C virus in
      blood donors].
AB  - 6,744 persons were examined for the presence of antibodies to hepatitis C virus
      (HCV) before blood donation (4,219 persons in Moscow and 2,525 persons in St.
      Petersburg). The serum samples found to contain antibodies to HCV were
      additionally studied by the immunoblot techniques. The positive results of
      antibody screening were registered in 78 persons: 26 persons in Moscow (0.62%)
      and 52 in St. Petersburg (2.05%). In both cities the positive results of
      screening were confirmed in 62% of cases. Different occurrence of the profile
      with the presence of antibodies to all fragments of the virus: 52% in Moscow, 12%
      in St. Petersburg (chi2 = 12.11; p < 0.001). Considerable differences were also
      registered in the spread of individual antibodies.

PMID- 16279541
TI  - [Detection of the markers of herpes simplex virus and cytomegalovirus in newborns
      and infants].
AB  - A total of 111 children suspected for herpesvirus infection were examined. In
      blood and urine samples the infectious activity of herpes simplex virus (HSV) and
      cytomegalovirus (CMV) was detected by the rapid culture method (RCM) and the
      presence of virus DNA--by the polymerase chain reaction (PCR). HSV and/or CMV
      were detected by two laboratory methods in 57 examined children (51%). Of these,
      in 18 children (16.2%) both HSV and CMV were detected. The coincidence of the
      results of the detection of HSV and CMV by these two methods was observed in
      72.4% and 75.2% of cases respectively. The comparative analysis of the detection
      of anti-CMV IgG and IgM was made with the use of commercial test systems produced
      bythe following manufacturers: "Vector-Best" and "Bioservice" (Russia), "HUMAN"
      and "Boehringer" (Germany). The effective detection of both anti-CMV (IgG and
      IgM) was ensured by the test systems "Boehringer". The test system "Vector-Best"
      for anti-CMV IgG proved to be not inferior as regards sensitivity and
      specificity. The German test systems demonstrated the highest specificity in the
      detection of low-avid antibodies. The data obtained in this study indicate that
      the detection rate of HSV and CMV markers in newborns and infants suspected for
      herpesvirus infection was, on the average, 20 - 40%. Reliable diagnostics in
      newborns and infants is possible only in the presence of the combination of at
      least 2 serological tests (the determination of antivirus IgM and IgG avidity)
      and 2 methods for the detection of direct herpesvirus markers (PCR and RCM).

PMID- 16279542
TI  - [Use of infusoria Paramecium caudatum for the evaluation of the toxicity of
      antigens of different causative quarantine agents].
AB  - The results of the evaluation of the toxicity of bacterial antigens obtained from
      the causative agents of plaque, glanders, melioidosis, cholera on infusoria of
      the species P. caudatum, as well as on cell lines L-929, CHO K-1 and peritoneal
      macrophages of BALB/c mice, are presented. As revealed in this study, the method
      of toxicity determination on infusoria is similar in its sensitivity to the
      methods of testing on. CHO K-1 and L-929 cells, but the former is simpler, more
      available and permits the determination of toxic doses producing disturbances in
      the vital activity of the infusoria, but not leading to their death.

PMID- 16279543
TI  - [Role of neutrophils in the regulation of the reproductive tract microbiocenosis
      in women].
AB  - The influence of neutrophils and their secretory products on the microflora of
      the vaginal contents in healthy women and in women having dysbiotic processes in
      the vagina was studied. The secretory products of neutrophils were found to
      produce a bactericidal effect on the representatives of the opportunistic
      bacteria, this effect being less pronounced with respect to lactic-acid bacteria.
      The established effect of neutrophils on bacteria is regarded as one of the
      mechanisms of microbiocenosis formation, ensuring colonization resistance.

PMID- 16279544
TI  - [Spectrum of antibodies to iron-regulated proteins in the blood sera of patients
      with meningococcal infection].
AB  - 55 paired sera from 25 patients with meningococcal infection (meningitis,
      meningococcemia) were studied with the use of immunoblotting. In these sera
      antibodies to 15 iron-regulated proteins (IRP) were detected. In the process of
      the development of meningococcal infection an increase in the content of specific
      antibodies to IRP with molecular weights of 35 kDa (38%), 43 kDa (52%) and 47 kDa
      (38%) was found to occur. The induction of antibodies did not depend on the group
      of the infecting strain, as well as on the patient's age.

PMID- 16279545
TI  - [Rodents as the vectors of infective agents in the natural foci of infections in
      the Moscow megapolis].
AB  - This work deals with the results of 40-year observations on the circulation of
      infective agents in the natural foci of infections (tularemia, leptospirosis,
      hemorrhagic fever with renal syndrome) among rodents and other small mammals in
      the territory of the Moscow. The monitoring of their frequency and the infection
      rates remains the main effective measure for the prophylaxis of dangerous
      infections among the population of the megapolis.

PMID- 16279547
TI  - [Evaluation of the epidemiological situation in different territories of the
      Russian Federation, based on the Bank of Standard Blood Sera].
AB  - The Bank of Standard Sera created in the Gamaleya Research Institute of
      Epidemiology and Microbiology provide for evaluation the epidemiological
      situation in any separate territory and in the whole of the country. The
      collection of certified blood sera is divided according to different territories
      of the country and makes it possible to obtain the retrospective and operative
      information on the level of population immunity and the immune structure of the
      population with respect to different infective agents, and to reveal the
      susceptible group of the population. The analysis of the unfavorable character of
      the epidemiological situation in the inspected territory with due consideration
      of its climato-geographical and anthropogenic environmental, socio-demographic
      characteristics, the level of population immunity and the immune structure of the
      population with respect to different infective agents makes it possible to carry
      out the epidemiological diagnostic (an outbreak, the import of infection, the use
      of a bacteriological weapon), prognosis and the prophylaxis of diseases, as well
      as the epidemiological cartography of territory.

PMID- 16279546
TI  - [Seroepidemiological characterization of virus hepatitis in the Republic of
      Armenia].
AB  - The survey of the population immunological structure with respect to parenteral
      hepatitis showed awide circulation of hepatitis B (HB) and hepatitis C (HC)
      viruses among the adult population of Armenia. During the 5 year period of
      observation the number of persons having antibodies to HC virus increased 2.7
      fold. High occurrence of antibodies to HBsAg of HB virus among the healthy
      population in 2002 (12.0%) in comparison with 1997 (5.4%) reflected a decreased
      infection rate with HB virus as well. Antibodies to hepatitis A (HA) virus were
      isolated, on the average, in 64 % of persons. Simultaneously with a decrease in
      the proportion of HA cases an increased number of HC patients was registered. No
      circulation of hepatitis E virus was detected. A high percentage of hepatitis
      cases of mixed etiology was established, as well as an increased number of
      combined parenteral hepatitis cases was registered (57.1%).

PMID- 16279548
TI  - [Level of IgE at different stages of HIV infection].
AB  - The content of total IgE in 109 patients at different stages of HIV infection are
      presented. The infection was at the asymptomatic stage in 30 patients, the stage
      of generalized lymphadenopathy in 29 patients, the stage of secondary
      manifestations in 36 patients, the stage of AIDS in 14 patients. The
      concentration of IgE was found to increase, on the average, at all stages of HIV
      infection (p < 0.001), the maximum level being observed at the stage of AIDS. The
      occurrence of high and low concentrations of total IgE was the same at the
      asymptomatic stage and the stage of generalized lymphadenopathy. At the stage of
      secondary manifestations the occurrence of low concentrations of IgE increased
      twofold. In the presence of parasitosis a significant rise in the content of
      total IgE was registered in HIV-infected patients.

PMID- 16279549
TI  - [Microbiological characterization of the causative agents of hospital infection
      in urological patients].
AB  - The analysis of the etiological structure of hospital infection in 52 urological
      patients has been carried out. The sensitivity of the causative agents of this
      infection to different antibiotics has been studied and recommendations on
      rational antibacterial therapy are given.

PMID- 16279550
TI  - [Levels of some cytokines and antibodies to hepatitis C virus in patients with
      chronic hepatitis C].
AB  - The comparison of the levels of some cytokines (tumor necrosis factor alpha (TNF
      alpha), IL-1beta, IL-2, IL-4) in the blood serum of patients with chronic
      hepatitis C (CHC) having different antibody spectrum was carried out. In CHC
      patients increased levels of the serum cytokines IL-1beta, TNF-alpha under study
      in comparison with cytokine levels in donor sera was noted. In patients with
      detected antiNS5 and antiHCV IgM and antiNS5 HCV the level of IL-1beta was
      significantly higher than that in CHC patients without antibodies in sera. A
      change in the levels of proinflammatory and anti-inflammatory cytokines in the
      blood sera of CHC patients may be of significant diagnostic and prognostic
      importance.

PMID- 16279551
TI  - [Substantiation of the composition, technology and standardization of the
      original medicinal forms of interferon and bactisporin].
AB  - New medicinal forms of immunobiological preparations--human lekocytic interferon
      and bactisporin--have been developed for local application in dentistry, surgery,
      gynecology. As the basis for these preparations, the pharmacopeial collagen
      solution has been used. The results obtained in this investigation indicate that
      the preparations are safe and possess wound-healing properties.

PMID- 16279552
TI  - [Concept of a probiotic preparation, containing original microbial metabolites].
AB  - The biological functions of Escherichia coli M-17 exometabolites, contained in
      the synthetic composition of the autostimulating preparation "Actoflor-C", were
      evaluated. As shown by in vitro experiments, the composition had higher
      stimulating activity with respectto some microorganisms of the normal microflora,
      in comparison with the prototype preparation "Actoflor". High doses of the
      preparation "Actoflor-C" were supposedly capable of having not only positive
      influence on the development of microbiocenosis, but also of producing
      therapeutic action and primarily on intestinal epithelial cells by compensating
      the insufficient supply of bacterial metabolites in dysbiotic states. The
      presented data made it possible to believe that the functional activity of
      microbiocenosis was greatly determined by the system of metabolic regulation. The
      presented results formed the basis for the use of bacterial metabolites in the
      therapeutic of microbiocenosis in man.

PMID- 16279553
TI  - [Rhinovirus diseases: pathogenesis, diagnostics and treatment].
AB  - Contemporary data on human rhinovirus diseases and their pathogenesis are
      presented. Special attention is paid to complications which may be caused by
      rhinovirus infections in allergy-susceptible patients. Furthermore, approaches to
      the diagnostics and treatment of rhinovirus diseases are described. In
      particular, the advantages of molecular methods for the diagnostics of rhinovirus
      infection (based on the PCR) in comparison with cultural and immunochemical
      methods are pointed out. New investigations aimed at the development of specific
      antirhinovirus preparations--capsid-binding (Pleconaril), blocking the binding of
      the virus with cell receptors (ICAM, soluble) and inhibiting rhinovirus protease
      3C--have been considered.

PMID- 16279554
TI  - [Morbidity in viral hepatitis A among population of the Kemerovo Region during
      the period of 1995 - 2003].

PMID- 16279555
TI  - European hazel (Corylus americana).

PMID- 16279556
TI  - Blocking aspirin-induced bronchospasm.

PMID- 16279557
TI  - Detection of causative foods by skin prick and atopy patch tests in patients with
      eosinophilic esophagitis: things are not what they seem.

PMID- 16279558
TI  - Personal protection against fire ants: what are the options?

PMID- 16279559
TI  - Treatment of ear pain in pilots in flight.

PMID- 16279560
TI  - The reading, writing, and arithmetic of the medical literature, part 2: critical
      evaluation of statistical reporting.
AB  - OBJECTIVE: To offer suggestions to help improve clinicians' understanding of the
      statistical analyses in the literature and their use of these methods in their
      own medical writings. DATA SOURCES: Literature searches began at the National
      Library of Medicine's online database and were traced to primary sources. STUDY
      SELECTION: All referenced information in this article was cited from primary
      sources. RESULTS: Physicians should be able to determine the variables studied
      and how they were measured, the comparisons that were made, the difference (with
      95% confidence interval) between the groups, the exact P value for the
      difference, the statistical test used in the analysis, whether the data conformed
      to the assumptions of the test, whether the study had adequate statistical power,
      and the clinical importance of the difference. CONCLUSION: Clinicians should know
      how to interpret statistical results so that they can use medical science to its
      full extent in treating patients.

PMID- 16279561
TI  - Recurrent streptococcal hepatic abscesses in a 46-year-old woman.

PMID- 16279562
TI  - The blocking effect of essential controller medications during aspirin challenges
      in patients with aspirin-exacerbated respiratory disease.
AB  - BACKGROUND: The blocking effect of controller medications for asthma could have
      an effect on the outcome of aspirin challenges in patients suspected of having
      aspirin-exacerbated respiratory disease (AERD). OBJECTIVE: To evaluate whether
      there was any blocking effect of long-acting beta2-agonists, systemic
      corticosteroids, and/or inhaled corticosteroids alone or as co-therapy with
      leukotriene modifier drugs (LTMDs). METHODS: Between 1981 and 2004, 678 patients
      with suspected AERD were admitted for aspirin challenge and desensitization. All
      patients had asthma, chronic sinusitis, nasal polyposis, and at least 1
      historical reaction to a nonsteroidal anti-inflammatory drug. Asthma controller
      medications taken during aspirin challenge were recorded and analyzed with
      respect to their potential effects on 4 possible outcomes of aspirin challenge,
      namely, naso-ocular reaction, lower airway reaction, classic upper and lower
      airway reaction, or a negative challenge result. RESULTS: When compared with AERD
      patients who received no controller medications, the combined use of LTMDs,
      inhaled corticosteroids, and long-acting beta2-agonists led to a statistically
      significant change in aspirin challenge outcomes (P = .009), mainly shifting the
      reaction from a classic upper and lower respiratory tract reaction to naso-ocular
      reactions only. LTMDs appeared to have the strongest effect (P < .001) in
      blocking lower respiratory tract reactions. Systemic corticosteroids did not have
      the same effects. Blocking of both upper and lower respiratory tract reactions to
      aspirin as a result of taking controller medications did not occur. CONCLUSION:
      Controller medications are frequently needed to stabilize airways of patients
      with AERD. LTMDs alone or in combination with other controllers blocked lower
      respiratory tract reactions during aspirin challenge in some patients with AERD
      but did not change the overall rate of positive aspirin challenge results and did
      not lead to false-negative challenges.

PMID- 16279563
TI  - Treatment of eosinophilic esophagitis with specific food elimination diet
      directed by a combination of skin prick and patch tests.
AB  - BACKGROUND: Eosinophilic esophagitis (EE) is a recently described disorder
      identified in patients with symptoms suggestive of gastroesophageal reflux
      disease (GERD) but unresponsive to conventional reflux therapies. Therapies have
      included corticosteroids, elemental diet, and diet restriction. We report our
      experience with skin prick and atopy patch testing and food elimination diets in
      patients diagnosed as having EE. OBJECTIVE: To identify food antigens that cause
      EE and the characteristics of patients who respond to food elimination vs those
      who are unresponsive. METHODS: Patients diagnosed as having EE had restricted
      diets based on skin prick and atopy patch testing results. Additional biopsies
      were performed after 4 to 8 weeks of restricted diet. Demographics, atopic
      tendencies, and food antigens were identified retrospectively in our food allergy
      database. RESULTS: A total of 146 patients diagnosed as having EE were evaluated
      with skin prick and atopy patch testing. Thirty-nine patients had unequivocal
      demonstration of food causing EE, with normalization of biopsy results on
      elimination and reoccurrence on reintroduction. An additional 73 patients, for a
      total 112 (77%) of 146 patients, had resolution of their EE as demonstrated by
      biopsy results. Fifteen (10%) of 146 patients were nonresponders manifested by no
      significant reduction in esophageal eosinophils despite restricted diet based on
      skin prick and atopy patch testing. Egg, milk, and soy were identified most
      frequently with skin prick testing, whereas corn, soy, and wheat were identified
      most frequently with atopy patch testing. CONCLUSION: In more than 75% of
      patients with EE, both symptoms and esophageal inflammation can be significantly
      improved with dietary elimination of foods. Skin prick and atopy patch testing
      can help identify foods in most patients.

PMID- 16279564
TI  - Personal protection measures against fire ant attacks.
AB  - BACKGROUND: Fire ant stings lead to significant morbidity and mortality each
      year. Virtually no information exists in the scientific literature about the
      effectiveness of personal protection measures against these ants. OBJECTIVES: To
      quantify the level of protection from ant stings by socks and cotton tights and
      to evaluate the efficacy of repellents and other chemicals in preventing stings.
      METHODS: Commercially obtained infant socks were fitted on a plastic doll's foot,
      which was touched to fire ant mounds in a series of controlled experiments. Socks
      and cotton tights were stretched over a human finger and placed in a fire ant
      mound to test the ability of ants to sting through fabric. Assays were developed
      to screen chemical substances for their ability to stop or prevent fire ant
      stings. RESULTS: Socks of any type reduced the number of fire ants that reached
      the skin and delayed the time required for ants to reach the skin above the sock
      level. Fire ants were unable to sting through all socks tested. Ants successfully
      stung both paper towels and human skin, regardless of chemical substance or
      repellent applied to them. CONCLUSIONS: Socks provide some degree of protection
      from fire ant stings; therefore, children living in fire ant-infested areas
      should wear them. Fire ants appear unable to sting through many commercially
      available socks. Cotton tights may be useful in protecting the lower extremities
      of children. Fire ants are not deterred from stinging by a wide variety of insect
      repellents and chemical substances.

PMID- 16279565
TI  - Allergic rhinitis and ear pain in flight.
AB  - BACKGROUND: Ear pain is the most common physiologic incident in hypobaric chamber
      training in the Japan Air Self-Defense Force, and the incidence of ear pain has
      been gradually increasing. There has been a concomitant increase in the incidence
      of allergic rhinitis in Japan. We hypothesized that the increased incidence of
      ear pain may be due to the increased incidence of eustachian tube dysfunction
      associated with allergic rhinitis. OBJECTIVE: To explore whether there is an
      association between allergic rhinitis and ear pain experienced in hypobaric
      chamber training. METHODS: We examined 9 years of training records and noted
      whether there was a seasonal influence on the occurrence of ear pain in 7047
      trainees. In addition, we studied the prevalence of allergic rhinitis among
      trainees during a representative training year using a questionnaire method,
      noting association between allergic rhinitis and the occurrence of ear pain.
      RESULTS: Comprehensive review of training records showed 429 (6.1%) of 7047
      trainees complained of ear pain. Ear pain occurred more often in spring than the
      other 3 seasons. The questionnaire data showed 202 (23.0%) of 878 trainees had
      allergic rhinitis. Trainees with allergic rhinitis complained of ear pain more
      often in the spring than trainees without allergic rhinitis. CONCLUSIONS: Active
      allergic rhinitis is closely associated with the occurrence of ear pain in
      hypobaric chamber training. A similar phenomenon might occur in an actual flight.
      Special attention should be paid to not only common cold but also allergic
      rhinitis in both hypobaric chamber training and actual flights.

PMID- 16279566
TI  - Cancer risk in asthmatic populations.
AB  - OBJECTIVE: To conduct a meta-analysis of epidemiologic studies to derive a pooled
      estimate of the association between asthma and cancer incidence and between
      allergy and cancer incidence. DATA SOURCES: Five cohort studies and 1 case
      control study of cancer incidence in asthma, 4 studies of cancer mortality in
      asthma, and 3 studies of cancer incidence in allergy. STUDY SELECTION: We
      searched the National Library of Medicine Gateway to identify observational
      studies of cancer incidence in asthma and included any case-control or cohort
      study of incident cancers or of cancer mortality that met the predefined
      inclusion criteria. RESULTS: There was no significant association between asthma
      and cancer incidence. A single large cohort study demonstrated a protective
      effect of asthma; the remaining cohort studies demonstrated a slightly elevated
      risk of cancer associated with asthma. Inconsistencies in study design features
      included control of smoking in analyses, use of a control group, and methods to
      identify asthma status. CONCLUSIONS: The method of asthma identification affects
      the validity of asthma classification and the severity of asthma examined. The
      inconsistency in study designs could have contributed to the variability in
      results and the underestimation of the impact of asthma on cancer incidence.

PMID- 16279567
TI  - Effects of adjuvant therapy with 0.1% olopatadine hydrochloride ophthalmic
      solution on quality of life in patients with allergic rhinitis using systemic or
      nasal therapy.
AB  - BACKGROUND: Allergic rhinoconjunctivitis patients are often treated with nasal or
      systemic allergy therapy, forgoing therapy for ocular symptoms. This treatment
      regimen leaves important aspects of the allergic reaction untreated and affects
      quality of life (QoL). The Rhinoconjunctivitis Quality of Life Questionnaire and
      the Allergic Conjunctivitis Quality of Life Questionnaire quantify separate
      aspects of QoL. OBJECTIVE: To determine the benefit gained in QoL, measured by
      these questionnaires, when antiallergy eyedrops (olopatadine) were added to
      patients' preexisting regimens of nasal or systemic allergic rhinitis treatment.
      METHODS: This was a 4-week prospective, multicenter, open-label, crossover,
      environmental QoL study. Visit 1 randomized patients to treatment group A or B
      and included baseline examinations and questionnaires. Group A instilled
      olopatadine twice daily and concomitantly with previously prescribed nasal or
      systemic antiallergy medication for 2 weeks. Group B received no ocular therapy
      and used only previously prescribed antiallergy medication for 2 weeks. Treatment
      group crossover occurred at visit 2. Patients again completed the questionnaires
      at visits 2 and 3. RESULTS: Two hundred patients completed the study, 97 in group
      A and 103 in group B. Groups A and B experienced ocular allergic symptoms for
      3.88 and 3.96 days, respectively, during the week before baseline. At visits 2
      and 3, questionnaire scores were significantly improved for each group when
      olopatadine was added compared with the nontreatment periods. By visit 2,
      olopatadine improved QoL by 49% compared with 5% in the nontreated group (P <
      .001). CONCLUSIONS: In this study, 90.5% of patients with allergic rhinitis
      treated nasally or systemically also had ocular allergic symptoms. Adding
      olopatadine to these patients' medication regimens significantly improved ocular
      allergic symptoms and overall QoL.

PMID- 16279569
TI  - Dermatophagoides extract-treated confluent type II epithelial cells (cA549) and
      human lung mesenchymal cell growth.
AB  - BACKGROUND: Chronic severe persistent asthma is associated with damaged
      epithelial cells with discontinuous tight junctions that contribute to
      dysregulated fibroblast and endothelial cell (mesenchymal) growth.
      Dermatophagoides species-derived proteases have been shown to cause damage to
      epithelial cell tight junctions. OBJECTIVE: To determine whether Dermatophagoides
      species can stimulate confluent A549 (cA549), a cell type with discontinuous
      tight junctions that approximate differentiated type II cells, to undergo altered
      growth and secrete putative soluble factors that affect the growth of human lung
      fibroblasts and microvascular endothelial cells. METHODS: Dialyzed
      Dermatophagoides pteronyssinus or Dermatophagoides farinae extracts (0, 300, 600,
      and 1000 AU/mL) were cultured with and without cA549 in serum-free media for 24
      hours. After changes in cA549 growth were recorded, conditioned media from
      extracts with cA549 (CM) and without cA549 (control media [CTLM]) were
      transferred to fibroblasts and endothelial cells for 24 hours. Fibroblast and
      endothelial cell growth responses to CM and CTLM were observed and measured.
      RESULTS: All conditions showed greater than 95% cell viability. Confluent A549
      showed dose-dependent growth changes characterized by increased aggregation when
      incubated with 300, 600, and 1000 AU/mL of D pteronyssinus in serum-free media
      relative to control. The CM, but not the CTLM, induced dose-dependent aggregation
      by fibroblasts and endothelial cells. Fibroblasts also showed decreased adhesion
      when incubated with CM. Dermatophagoides farinae-treated cA549 showed similar but
      weaker results. The use of serum, boiled CM, or boiled extract inhibited these
      findings. CONCLUSIONS: Dialyzed Dermatophagoides species extracts altered cA549
      growth and stimulated the secretion of factors that dysregulate mesenchymal cell
      growth in vitro.

PMID- 16279568
TI  - Effects of montelukast treatment on clinical and inflammatory variables in
      patients with cystic fibrosis.
AB  - BACKGROUND: In cystic fibrosis (CF), the inflammatory process contributes to
      progressive lung tissue damage. Cysteinyl leukotrienes have been found in the
      sputum of patients with CF at high concentrations sufficient to cause potent
      biological effects. OBJECTIVE: To evaluate the effect of anti-inflammatory
      treatment with montelukast sodium in patients with CF. METHODS: Twenty-six
      patients aged 6 to 18 years were recruited to this 20-week, randomized, double
      blind, placebo-controlled, crossover trial. Patients received montelukast or
      placebo for 8 weeks in addition to their regular CF treatment. Before and after
      treatment, findings from spirometry, whole-body plethysmography, and the clinical
      wheezing and cough scales were evaluated. At the same time, serum and sputum
      samples were obtained for the measurement of eosinophil cationic protein,
      interleukin 10 (IL-10), IL-8, and myeloperoxidase levels. RESULTS: Twenty-three
      patients completed the study. Compared with placebo use, montelukast treatment
      significantly improved forced expiratory volume in I second, peak expiratory
      flow, and forced expiratory flow between 25% and 75% and significantly decreased
      cough and wheezing scale scores (P < .001 for all). There were no significant
      changes in vital capacity, thoracic gas volume, airway resistance, and residual
      volume after treatment. Compared with placebo use, montelukast treatment
      decreased serum and sputum levels of eosinophil cationic protein and IL-8,
      decreased sputum levels of myeloperoxidase, and increased serum and sputum levels
      of IL-10 (P < .001 for all). CONCLUSIONS: Montelukast may have measurable anti
      inflammatory properties in patients with CF.

PMID- 16279570
TI  - Intraoperative anaphylaxis to bacitracin during pacemaker change and laser lead
      extraction.
AB  - BACKGROUND: Bacitracin is widely used in operating rooms to soak implants,
      irrigate compound fractures, and apply to surgical incisions. However, bacitracin
      is a known sensitizer and causes not only allergic contact dermatitis but also
      anaphylaxis. OBJECTIVE: To describe a 72-year-old woman with anaphylaxis after
      irrigation and packing of an infected pacemaker pocket with a bacitracin
      solution. METHODS: Skin prick testing to bacitracin and latex; serum tryptase,
      serum histamine, serum IgE to latex, and serial cardiac enzyme measurements;
      blood cultures, transthoracic echocardiograms, and venograms were performed to
      characterize the reaction. RESULTS: Six hours after the anaphylactic event, the
      patient had an elevated serum tryptase level of 49 ng/mL (reference range, 2-10
      ng/mL), which normalized the next morning. She had immediate-type skin prick test
      reactions to full-strength bacitracin ointment (500 U/g) and bacitracin solution
      (150 U/mL). Serum IgE level to latex was undetectable, and results of skin
      testing to latex were negative. CONCLUSIONS: To our knowledge, this is the first
      case report of anaphylaxis to bacitracin during pacemaker surgery. This case
      illustrates that intraoperative anaphylaxis to bacitracin can be life
      threatening.

PMID- 16279571
TI  - Neutrophil chemotaxis in a patient with neonatal-onset multisystem inflammatory
      disease and Muckle-Wells syndrome.
AB  - BACKGROUND: Neonatal-onset multisystem inflammatory disease (NOMID)/chronic
      infantile neurologic, cutaneous, and articular syndrome is an autoinflammatory
      disease characterized by urticarial rash, arthropathy, and central nervous system
      inflammation. OBJECTIVE: To describe a 13-year-old girl with overlapping symptoms
      of NOMID and Muckle-Wells syndrome who has a mutation in cryopyrin (NALP3).
      METHODS: We examined neutrophil migration using transwell assay and time-lapse
      videomicroscopy. We also examined p38 mitogen-activated protein kinase (MAPK)
      activation in patient and control neutrophils using Western blot analysis.
      RESULTS: Neutrophil defects in chemotactic migration were found to a variety of
      chemoattractants, including interleukin 8, N-formyl-methionyl-leucyl
      phenylalanine, complement C5a, and leukotriene B4. Her neutrophils exhibited
      elevated basal and stimulated p38 MAPK activation in response to interleukin 8, N
      formyl-methionyl-leucyl-phenylalanine, complement C5a, and leukotriene B4.
      CONCLUSIONS: This study is the first, to our knowledge, to demonstrate defects in
      neutrophil chemotaxis and p38 MAPK signaling in a patient with NOMID and Muckle
      Wells syndrome and a cryopyrin mutation.

PMID- 16279572
TI  - The science of web-based clinical trial management.

PMID- 16279573
TI  - Consumer and researcher collaboration in trials: filling the gaps.

PMID- 16279574
TI  - Optimal two-stage randomized phase II clinical trials.
AB  - Randomized phase II clinical trials can be an efficient means of evaluating
      several potential new treatments prior to a comparative phase III clinical trial.
      However, selection designs do not allow for an assessment of minimal efficacy,
      nor do they allow early closing of a study arm for lack of efficacy, and so are
      only appropriate when all arms have met minimal efficacy requirements. Classic
      two-stage hypothesis testing based designs such as a Simon two-stage optimal
      design can satisfy these requirements, when used in parallel for the multiple
      treatment arms. However, these can be inefficient and impractical in terms of the
      maximum planned sample size required for such a study. This article proposes a
      two-stage randomized phase II clinical trial, where the sample size is adaptive
      at the second stage to the number of treatment arms passing through the first
      stage. The study design relies on optimality criteria, which are analogous to
      those used by Simon for single-arm studies. The proposed design maintains similar
      operating characteristics to a strategy of using multiple single-arm studies, in
      most situations of primary interest. Furthermore, it generally has smaller actual
      sample size when most of the treatments are effective than using multiple single
      arm studies, leading to substantial efficiencies in terms of maximum planned
      sample size.

PMID- 16279575
TI  - Experimental designs for multicomponent interventions among persons with
      multifactorial geriatric syndromes.
AB  - This paper discusses issues about the design of clinical trials to test
      multicomponent interventions for multifactorial health conditions, such as
      geriatric syndromes in which more than one risk factor is related to the outcome.
      The issues covered include: identification and selection of modifiable risk
      factors related to the outcome of interest, selection of intervention components
      to reduce the deleterious effects of the modifiable risk factors, assignment of
      components of the intervention, blinding, sample size requirements and estimation
      of component effects. Each of these issues is explored using examples from nine
      illustrative multicomponent intervention trials. Statistical and clinical
      concerns regarding the design of multicomponent interventions are addressed. We
      also propose elements of multicomponent interventions for multifactorial health
      conditions that should be reported in publications and areas where future
      research is needed.

PMID- 16279576
TI  - Data monitoring in randomized controlled trials: surveys of recent practice and
      policies.
AB  - BACKGROUND: Data Monitoring Committees (DMCs) are increasingly involved in the
      conduct of randomized controlled trials, but there is little documented evidence
      of what they do. Three interlinked surveys were carried out as part of the
      DAMOCLES project to explore recent and current DMC practice and policy. METHODS:
      1) A questionnaire about DMC practice was sent to sample of 45 authors of trials
      published in selected journals in 2000. The sample was stratified by centre
      (single/multiple), disease area, and presence of DMC. 2) A sample of
      investigators in trials ongoing in the United Kingdom in 2001-02 was also sent a
      questionnaire about DMC practice. The sample was drawn from trials funded by the
      Medical Research Council, the United Kingdom Department of Health's Health
      Technology Assessment Programme, and a local and a multicentre research ethics
      committee. The sample was additionally stratified by funder (public/industry),
      centre (single/ multiple), and disease area. 3) A sample of major organisations
      involved in randomised controlled trials was sent a questionnaire about DMC
      policies. RESULTS: Information about DMC practice from the first survey was
      obtained from 31 trials (69%), of which four had a DMC. Information about DMC
      practice from the second survey was obtained about 36 trials (90%), of which 20
      had a DMC. Information about DMC policy from the third survey was obtained from
      25 out of 25 organisations. There was general agreement about the sorts of trials
      particularly needing independent DMCs, but there were few uniform approaches to
      their modes of functioning, and few of the organisations surveyed had developed
      formal policies. CONCLUSIONS: The roles of existing DMCs and policies governing
      DMC functioning vary widely across trials and organisations that sponsor or
      oversee trials, both within the UK and internationally. These findings reinforce
      previous calls for development of such policies across a wider range of
      organisations, better means to monitor their implementation within trials, and
      wider use of structured "charters", which set out DMC modus operandi in advance.
      Clinical Trials 2005; 2: 22-33. www.SCTjournal.com

PMID- 16279577
TI  - Evaluating the quality of informed consent.
AB  - CONTEXT: Although informed consent is a critical means of protecting the rights
      and interests of participants in clinical research, effective and efficient means
      of evaluating the quality of consent are needed. Having such means will be
      important to monitoring consent and testing potential improvements in the consent
      process. OBJECTIVE: To develop and test a practical and general means of
      evaluating the quality of informed consent for clinical research. Methods We
      developed and tested the Brief Informed Consent Evaluation Protocol (BICEP), a
      short telephone-based assessment of informed consent. As soon as patient
      participants completed the informed consent process for a participating VA
      Cooperative Studies Program clinical trial they called an interviewer who
      administered the BICEP. RESULTS: 632 participants completed BICEP, representing
      eight ongoing studies from 14 VA and one non-VA medical centers across the
      country. Site coordinators reported little to no difficulty implementing BICEP.
      The average duration of BICEP was 8.8 minutes (SD 3.6). Overall, patient
      participants evaluated the informed consent process positively. A reliable coding
      system was then developed to analyze the verbatim responses of the final 191
      participants. An Informed Consent Aggregate Score (ICAS) had a mean score of 8.23
      (SD 1.17) with a range of 0-10, with 10 a perfect score; and a Therapeutic
      Misconception Aggregate Score (TMAS) had a mean of 1.62 (SD 0.93) with a range of
      0-5, with 5 a perfect score. CONCLUSIONS: The BICEP is an efficient means of
      evaluating informed consent that is acceptable to research participants and
      research personnel. While participants tend to be satisfied with the informed
      consent process, the BICEP indicates there is room for improvement in the
      informed consent process for research.

PMID- 16279578
TI  - A web-based system for managing and co-ordinating multiple multisite studies.
AB  - Efficient and secure collection and management of information is essential in any
      modern biomedical study. Data management and coordination of multisite studies is
      a complex process. It involves development of systems for data collection, data
      cleaning with quality assurance checks, and specimen tracking, as well as
      development of procedures for conducting the study, training clinical sites, and
      communicating with sites to answer study questions and resolve and track data
      inquiries and resolutions. We developed a secure web-based system that is
      designed to automate evaluation of eligibility criteria and data collection,
      track specimens, serve as a resource for study-specific information, facilitate
      communication across sites in multisite studies, track data queries and
      resolutions, and allow administrative management of studies. The system combines
      a common framework across studies that defines the internal structure for all the
      web pages, with a study-specific one that defines the content of each page via a
      relational database. This combination creates a flexible and efficient
      environment enabling several multisite studies to be simultaneously or
      consecutively implemented and managed in a timely manner. We describe the
      development process, the system and its evaluation, current status, lessons
      learned, and future development plans.

PMID- 16279579
TI  - Web-based distributed data management in the childhood asthma research and
      education (CARE) network.
AB  - A well-designed distributed data management application provides an efficient,
      effective process to collect quality data in multicenter clinical trials. This
      paper describes the web-based clinical center data management application that
      was developed by the Data Coordinating Center of the Childhood Asthma Research
      and Education (CARE) Network. A series of modules was designed to allow the
      clinical staff at the remote clinical centers to enter clinical trial data,
      correct entry errors, respond to queries from the Data Coordinating Center, and
      submit data corrections for previously entered data to ultimately provide a clean
      and accurate dataset for analysis.

PMID- 16279580
TI  - A unified web-based query and notification system (QNS) for subject management,
      adverse events, regulatory, and IRB components of clinical trials.
AB  - Even after intensive review, interpretative questions, ambiguities,
      contradictions, or errors, will arise once the protocol is scrutinized by site
      IRBs and implemented at sites. This will occur despite preparation and
      implementation of site protocol training, and provision of well crafted case
      report forms for the reporting of clinical and laboratory evaluations and adverse
      events. Since many staff are involved in each protocol, site investigators or
      study coordinators might direct protocol queries, participant management, or IRB
      queries to different network participants, resulting in inconsistent responses.
      It is important to establish a response mechanism that ensures consistent
      responses and their systematic documentation. For reporting of adverse events,
      and the submission of or documentation of completion of regulatory requirements,
      an easily accessible and structured communications system is also required. This
      paper describes the development and implementation of a user-friendly web-based
      query and notification system (QNS) for subject management, adverse events,
      regulatory, and IRB components. This system was created in the Adolescent Trials
      Network for HIV/AIDS Interventions (ATN), using existing web based tools with
      minor modifications and minimal cost. The query and notification system is
      interactive and allows for free flow of information among the site coordinators
      and both the protocol teams and the regulatory group. The process of the system
      is transparent to users at the sites, although its use and maintenance is
      controlled by Data Operations Center staff, to assure that ATN requirements for
      review and approval are met. This results in consistency of and timeliness of
      responses to queries, timeliness and accuracy of adverse event reporting and the
      ability for the data operations center regulatory staff to provide notification
      of pending or delinquent regulatory submissions.

PMID- 16279581
TI  - Is the future for clinical trials internet-based? A cluster randomized clinical
      trial.
AB  - OBJECTIVE: To compare the efficiency and ease of use of internet data capture
      compared with conventional paper based data recording in the conduct of a
      clinical trial. DESIGN: Multicentre, cluster randomized clinical trial. SETTING:
      General practice in the UK. MAIN OUTCOME MEASURES: Timings for study landmarks,
      queries, data entry and monitoring time; Investigator Questionnaire Results.
      RESULTS: The internet-derived database was ready for release 33 days after the
      last patient visit compared with 48 days for the paper-derived database, despite
      much higher numbers of patients in the internet group. The mean times from visit
      to data entry were 10.2 (SD 18.9) days and 95.4 (SD 44.6) days respectively (P <
      0.01). The mean times from a visit to a query being resolved were 121.4 (SD 58.3)
      days and 182.1 (SD 58.9) days respectively (P < 0.01). The post-study responses
      from investigators were positive. Seventy-one percent of centres said they would
      prefer to use the internet rather than paper CRFs for future studies.
      CONCLUSIONS: There were efficiency gains seen with the use of an internet-based
      system when compared with a paper-based system in terms data entry, query
      resolution and the time to the release of the database. The investigators'
      response to the internet system was generally favourable although on average
      investigators reported increased time spent on the study. Further efficiency
      might be gained with improved programming, increased investigator familiarity
      with the internet system, and with newly adapted working practices for sponsors'
      monitors and database personnel.

PMID- 16279582
TI  - An integrated approach to consumer representation and involvement in a
      multicentre randomized controlled trial.
AB  - Although, consumer involvement in individual studies is often limited, their
      involvement in guiding health research is generally considered to be beneficial.
      This paper outlines our experiences of an integrated relationship between the
      organisers of a clinical trial and a consumer organisation. The PRISM trial is a
      UK multicentre, randomized controlled trial comparing treatment strategies for
      Paget's disease of the bone. The National Association for the Relief of Paget's
      Disease (NARPD) is the only UK support group for sufferers of Paget's disease and
      has worked closely with the PRISM team from the outset. NARPD involvement is
      integral to the conduct of the trial and specific roles have included: peer
      review; trial steering committee membership; provision of advice to participants,
      and promotion of the trial amongst Paget's disease patients. The integrated
      relationship has yielded benefits to both the trial and the consumer
      organisation. The benefits for the trial have included: recruitment of
      participants via NARPD contacts; well-informed participants; unsolicited patient
      advocacy of the trial; and interested and pro-active collaborators. For the NARPD
      and Paget's disease sufferers, benefits have included: increased awareness of
      Paget's disease; increased access to relevant health research; increased
      awareness of the NARPD services; and wider transfer of diagnosis and management
      knowledge to/from health care professionals. Our experience has shown that an
      integrated approach between a trial team and a consumer organisation is
      worthwhile. Adoption of such an approach in other trials may yield significant
      improvements in recruitment and quality of participant information flow. There
      are, however, resource implications for both parties.

PMID- 16279583
TI  - Problem we must come to grips with.

PMID- 16279584
TI  - Transintestinal oxygenation with perfluorocarbon: investigation of perfusion
      rate.
AB  - OBJECTIVE: Perfluorocarbons are structurally similar to hydrocarbons but with the
      hydrogen atoms replaced by fluorine. In general, perfluorocarbons have an
      excellent oxygen and carbon dioxide carrying capacity. We studied the suitability
      of oxygenated perfluorocarbon as an agent for transintestinal oxygenation and
      measured its perfusion rates under different conditions. SUBJECTS AND METHODS: We
      used FC-77 (Sumitomo 3M, Tokyo, Japan) perfluorocarbon and a rat hypoventilation
      model (room air, 20 breaths/min, a tidal volume of 10 ml/kg). Oxygenated FC-77
      was perfused through the small intestine for 4 hours. Rats were allocated to 3
      experimental groups according to the perfusion rate and a control group: Group 1
      (n=6), 10 ml/min; Group 2 (n=6), 2.5 ml/min; Group 3 (n=6), 0.75 ml/min; Group 4
      (n=6) served as a control (hypoventilation only). Arterial blood samples were
      drawn every 30 minutes. Standard blood gas analysis was performed. RESULTS: After
      four hours of perfusion, the PaO2 levels in Groups 1 to 3 were significantly
      better than Group 4 (p<0.01, Group 1: 141.7 +/- 18.0 mmHg, Group 2: 145.2 +/-
      25.1 mmHg, Group 3: 120.5 +/- 21.2 mmHg, Group 4: 67.4 +/- 7.2 mmHg). PaCO2
      levels in Groups 1 and 2 were significantly better than Groups 3 and 4 (p<0.01,
      Group 1: 42.6 +/- 7.2 mmHg, Group 2: 52.1 +/- 7.7 mmHg, Group 3: 78.2 +/- 22.8
      mmHg, Group 4: 75.3 +/- 10.3 mmHg). CONCLUSION: In the present settings, 8
      ml/kg/min was adequate for oxygenation and CO2 clearance. This approach promises
      to become another modality for respiratory assistance.

PMID- 16279585
TI  - Mitral valve replacement in children under 3 years of age.
AB  - OBJECTIVE: This study was undertaken to review our experience of mitral valve
      replacement in children under 3 years of age. METHODS: Between January 1990 and
      May 2004, 18 patients under 3 years of age underwent a total of 20 mitral valve
      replacements using a bileaflet mechanical prosthetic valve. There were 9 males
      and 11 females. The age at surgery ranged from 3 months to 3 (mean=1.02 +/- 0.72)
      years and body weight varied between 3.4 and 13.2 (mean=7.08 +/- 2.74) kg.
      RESULTS: There were 4 early and 2 late deaths, and these occurred in severe cases
      aged less than 1 year of age. Re-replacement of mitral valve was required in 3
      patients (valve thrombosis in 2 and pannus formation in 1). Orifice size of the
      implanted prosthesis (OS) as compared with the predicted normal size of the
      mitral valve (NS) was well correlated with maximum transprosthetic flow velocity
      estimated by Doppler echocardiography. In this study, the OS/NS>0.65 was
      maintained in all patients, and none required re-replacement because of
      prosthesis-patient mismatch. CONCLUSION: Patients less than 1 year of age had
      significant mortality and morbidity. The results were satisfactory in the
      remainder (1-3 years). During this follow-up period, none required re-replacement
      due to somatic growth, but it will be an unavoidable problem in the future. The
      OS/NS, which can be checked with a regular physical examination, may serve as a
      guide to determine the most appropriate timing for the second surgery.

PMID- 16279586
TI  - Learning curve of coronary surgery by a cardiac surgeon in Japan with the use of
      cumulative sum analysis.
AB  - OBJECTIVE: Case-volume has been believed to be of paramount importance in
      becoming a good cardiac surgeon. However, for a training cardiac surgeon there is
      no evidence regarding the specific number of necessary cases to attain the medico
      legally acceptable level. We attempted to observe the learning curve in
      performing coronary surgery with the use of the cumulative sum (CUSUM) method to
      provide some evidence. METHODS: From April 2000 to March 2004, a cardiac surgeon,
      being board-certified but not being on the attending staff, performed 50 coronary
      artery bypass grafting (CABG) under supervision of three different chief
      attending surgeons at three different hospitals. His learning curve was analyzed
      with the use of CUSUM. Mortality and morbidity and the average time of crossclamp
      and operation at each hospital were examined. Also, the learning curve of 100
      left internal mammary artery (LIMA) harvestings were analyzed via CUSUM in terms
      of harvesting time and injury rate. RESULTS: The CUSUM curve tended to come
      closer to the alert line (0.80 confidence) until the 23rd case, but never reached
      the alert line thereafter until the 50th case. The CUSUM curve never transgressed
      the alarm line (0.95 confidence) throughout 50 cases. The CUSUM curve of LIMA
      harvesting approached the alert line in the 38th case and the 59th case, but
      thereafter never reached the alert line and remained below the reassurance line
      from the 73rd case. CONCLUSION: Tentatively, it is inferred that approximately 23
      cases of CABG may be sufficient to allow for independent practice and that 73
      cases of LIMA harvesting are sufficient to allow independent practice.

PMID- 16279587
TI  - Long-term evaluation of bovine pericardial bioprostheses in young women:
      influence of pregnancy.
AB  - OBJECTIVES: To avoid the fetal and maternal risks associated with anticoagulant
      therapy during pregnancy, the use of bioprostheses has been advocated for young
      women with cardiac valve disease during the childbearing years. Several reports
      have suggested the probability of pregnancy-related accelerated structural valve
      deterioration (SVD). The aim of this study was to assess the effect of pregnancy
      and delivery on bovine pericardial bioprostheses. METHODS: Between 1986 and 2004,
      13 female patients received 14 bioprostheses. The women were segregated into two
      groups based on whether pregnancy occurred during follow-up: eight in the
      Pregnant Group (Group P) (including one case who underwent two operations), and
      six in the Nonpregnant Group (Group NP). RESULT: Early mortality was not
      observed. Late mortality was 12.5% for Group P and 16.7% for Group NP. There were
      a total of ten valve-related reoperations (seven in Group P and three in Group
      NP); the major reason was SVD in 64.3% of the cases. Freedom from valve-related
      reoperation at nine years was 28.6% in Group P and 33.3% in Group NP (p=0.338).
      Overall time from primary surgery to reoperation was 111 +/- 24.7 months, with no
      significant difference between the two groups (p=0.615). The Group P of eight
      patients had 12 pregnancies: ten deliveries and two abortions. There were no
      maternal or neonatal deaths. CONCLUSION: Pregnancy did not significantly
      influence the incidence of SVD and reoperation. The bioprostheses appears to
      provide female patients with more opportunity for uncomplicated pregnancies,
      deliveries and normal children than mechanical valves.

PMID- 16279588
TI  - Early onset of ganciclovir-resistant cytomegalovirus infection in a lung
      transplant recipient.
AB  - Ganciclovir resistance in cytomegalovirus (CMV) is an increasing problem in lung
      transplant recipients with adverse clinical outcomes. We experienced the
      successful treatment of ganciclovir-resistant CMV infection in a lung-transplant
      recipient still receiving CMV prophylaxis. A 24-year-old woman with
      lymphangioleiomyomatosis underwent a living-donor lobar lung transplantation. She
      was a primary CMV mismatch (D+/R-) patient. She recovered from her postoperative
      complications, and was about to be discharged. However, she suffered ganciclovir
      resistant CMV infection during prophylactic therapy. She was successfully treated
      with foscarnet, and is now alive without recurrence 18 months after surgery.

PMID- 16279589
TI  - Video-assisted thoracoscopic resection of a giant anterior mediastinal tumor
      (lipoma) using an original sternum-lifting technique.
AB  - We report here the complete thoracoscopic resection of a giant lipoma (18x15x5
      cm, 560 g) in a 33-year-old man using an original sternum-lifting technique. The
      patient had an uncomplicated postoperative course and was discharged on the
      seventh postoperative day. This is the largest reported anterior mediastinal
      tumor that was completely resected by video-assisted thoracic surgery without
      median sternotomy or thoracotomy. This original method may be useful from the
      standpoint of minimal access, rapid recovery, less pain, and good cosmetic
      results for an anterior mediastinal giant tumor.

PMID- 16279590
TI  - Gastric tube-to-pleural fistula seventeen months after esophagectomy: successful
      endoscopic treatment of an unusual complication.
AB  - A gastric tube-to-pleural fistula is an uncommon late complication of
      esophagectomy. In this report, a 71-year-old man who developed gastric tube-to
      pleural fistula 17 months after esophagectomy with intrathoracic reconstruction
      using a gastric tube is presented. Chest radiograph on admission showed massive
      right pleural effusion, which demonstrated empyema on chest drainage. Further
      imaging studies confirmed a gastric tube-to-pleural fistula that had no
      connection to the airway. We chose endoscopic intervention as a less invasive
      procedure and successfully treated the patient by plugging fibrin glue into the
      fistula under endoscopy. Review of the literature and discussion of the clinical
      features, differential causes, and treatment options of this rare and severe
      condition are presented.

PMID- 16279591
TI  - Anomalous systemic arterial supply to the basal segments of the left lung with
      two aberrant arteries.
AB  - A 30-year-old man was admitted to our hospital because of hemoptysis. Digital
      subtraction aortography revealed an anomalous systemic artery (10 mm diameter)
      from the descending thoracic aorta to the basal segments of the left lung. The
      presence of another smaller aberrant artery from the abdominal aorta was strongly
      suspected on the basis of aortography. We confirmed the presence of a smaller
      aberrant artery (3 mm diameter) traversing the pulmonary ligament after
      thoracotomy. We performed left lower lobectomy with resection of the two aberrant
      arteries via posterolateral thoracotomy with a favorable postoperative outcome.
      Although it is rare, the possibility of the presence of several aberrant arteries
      should be considered in anomalous systemic arterial supply to the basal segment
      of the left lung. Preoperative identification of aberrant arteries was useful for
      a safe operative procedure.

PMID- 16279592
TI  - Aortic valve lipomatous hamartoma in a young woman.
AB  - We present a rare case of lipomatous hamartoma of the aortic valve. A 17-year-old
      woman was admitted with cardiac murmur. Echocardiography demonstrated severe
      aortic regurgitation and a highly echoic mass on the right cusp of the aortic
      valve. Surgery was performed with a differential diagnosis of chronic infective
      endocarditis or aortic valve tumor. At operation, a yellowish bead-shaped tumor
      was detected on the right cusp of the aortic valve, and aortic valve replacement
      was performed. Histopathological examination confirmed a lipomatous hamartoma. To
      the best of our knowledge, this is the first reported case of a lipomatous
      hamartoma located on the aortic valve.

PMID- 16279593
TI  - Successful treatment of an adult patient with pulmonary abscess secondary to
      congenital cystic adenomatoid malformation.
AB  - We report a case of a 29 year old male who at age 25, developed a pulmonary
      abscess in the left lower lobe. A left lower lobectomy was performed following
      two recurrences on antibiotic treatment. The result of histopathological
      examination confirmed congenital cystic adenomatoid malformation (CCAM), a
      congenital disease characterized by multiple cysts resulting from adenomatous
      hyperplasia of the bronchial epithelia. In many cases, respiratory distress
      occurs during the neonatal period, and in about 80-85% of patients, CCAM is
      diagnosed before the age of two years due to respiratory infection. CCAM which
      was diagnosed in adulthood is very rare.

PMID- 16279594
TI  - Mediastinal malignant fibrous histiocytoma developing from a foreign body
      granuloma.
AB  - A patient with mediastinal malignant fibrous histiocytoma (MFH) apparently
      developing from a foreign body granuloma is reported. A 72-year-old man was
      admitted to our hospital complaining of generalized fatigue and palpitations. He
      had undergone surgery for pulmonary tuberculosis 46 years previously. Radiography
      and computed tomography of the chest showed a round 5-cm mass with marginal
      calcification in the right side of the anterior mediastinum. The mass was
      resected completely via median sternotomy. Intraoperative diagnosis of foreign
      body granuloma was made, based on gauze fragments found in the mass and
      intraoperative pathologic findings suggesting benign granulation tissue. The
      postoperative histopathologic diagnosis was myxoid MFH. To our knowledge,
      mediastinal MFH developing from a foreign body granuloma has not been reported
      previously.

PMID- 16279595
TI  - [Discovery and significance of thyroid hormone and its receptors].

PMID- 16279596
TI  - [Receptor-mediated nongenomic action of thyroid hormone: T3-dependent activation
      of PI3K-->akt/PKB-->mTOR signaling cascade, leading to the upregulation of ZAKI
      4alpha, a calcineurin inhibitor].

PMID- 16279598
TI  - [Mutations of the thyroid peroxidase gene].

PMID- 16279597
TI  - [Physiological and pathological significance of Na/I symporter gene and PDS gene
      on the thyroid function].

PMID- 16279599
TI  - [Thyroglobulin gene abnormalities].

PMID- 16279600
TI  - [Iodothyronine deiodinases and thyroid hormone metabolism].

PMID- 16279601
TI  - [Signal transduction by thyroid hormone receptors].

PMID- 16279602
TI  - [Animals with targeted mutations in thyroid hormone receptors].

PMID- 16279603
TI  - [Thyrotropin receptor and signal transduction].

PMID- 16279604
TI  - [Mouse model of Graves' disease].

PMID- 16279605
TI  - [Expression and function of the thyrotropin-releasing hormone (TRH)].

PMID- 16279607
TI  - [Effects of thyroid hormone on function and development of the brain].

PMID- 16279606
TI  - [Effects of thyroid hormone on growth and energy expenditure].

PMID- 16279608
TI  - [Effects of thyroid hormone on hematopoiesis].

PMID- 16279609
TI  - [Primary hypothyroidism].

PMID- 16279610
TI  - [Central hypothyroidism].

PMID- 16279611
TI  - [Resistance to thyroid hormone].

PMID- 16279612
TI  - [Congenital hypothyroidism].

PMID- 16279613
TI  - [Chronic thyroiditis (Hashimoto's disease)].

PMID- 16279614
TI  - [Basedow's disease].

PMID- 16279615
TI  - [Subacute thyroiditis and silent thyroiditis].

PMID- 16279616
TI  - [Nonthyroidal illness].

PMID- 16279617
TI  - [Thyroxine-binding globulin abnormalities].

PMID- 16279618
TI  - [Drug (amiodarone)-induced thyroid disease].

PMID- 16279619
TI  - [Nongenomic effects of thyroid hormones].

PMID- 16279620
TI  - [Mechanism of abnormal thyroid cell proliferation in normal and tumor tissues].

PMID- 16279621
TI  - [Genetic abnormality in thyroid cancers].

PMID- 16279622
TI  - [Discovery and significance of calcitonin].

PMID- 16279623
TI  - [Gene, structure, and biosynthesis of calcitonin].

PMID- 16279625
TI  - [Calcitonin receptor and its signal transduction].

PMID- 16279624
TI  - [Correlation between structure and bioactivity of calcitonin].

PMID- 16279626
TI  - [Distribution and regulation of calcitonin expression].

PMID- 16279627
TI  - [Calcitonin gene modified animals].

PMID- 16279628
TI  - [Calcitonin receptor gene recombinant animals].

PMID- 16279629
TI  - [Calcitonin assay].

PMID- 16279630
TI  - [Inhibitory effects of calcitonin on bone resorption].

PMID- 16279631
TI  - [Effect of calcitonin on the transport of Ca, Mg and PO4 across the small
      intestine].

PMID- 16279632
TI  - [Calcitonin actions on kidney].

PMID- 16279633
TI  - [Mechanism of antinociceptive action of calcitonin--involvement of descending
      serotonergic system].

PMID- 16279634
TI  - [Calcitonin in the pathogenesis and treatment of osteoporosis].

PMID- 16279635
TI  - [Paget's disease of bone].

PMID- 16279636
TI  - [Chronic renal failure].

PMID- 16279638
TI  - [Translational research on calcitonin].

PMID- 16279637
TI  - [Hyperparathyroidism].

PMID- 16279639
TI  - [Calcitonin receptor-stimulating peptides].

PMID- 16279640
TI  - [EBM of calcitonin].

PMID- 16279641
TI  - [Perspective for the new calcitonin preparation].

PMID- 16279642
TI  - [Gene, structure, synthesis, and expressional regulation of calcitonin gene
      related peptide].

PMID- 16279643
TI  - [Structural and pharmacological features of calcitonin gene-related peptide
      receptor subtypes].

PMID- 16279645
TI  - [Recent development of calcitonin gene-related peptide (CGRP) receptor
      antagonist].

PMID- 16279644
TI  - [Physiological actions of calcitonin gene-related peptide].

PMID- 16279647
TI  - [Gene, structure and biosynthesis of parathyroid hormone].

PMID- 16279646
TI  - [Discovery and significance of parathyroid hormone].

PMID- 16279648
TI  - [Parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor and the signal
      transduction].

PMID- 16279649
TI  - [Parathyroid hormone--its localization and transcriptional regulation].

PMID- 16279650
TI  - [Experimental animal models of primary hyperparathyroidism].

PMID- 16279651
TI  - [Parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor gene recombinant
      mice].

PMID- 16279652
TI  - [New assay for parathyroid hormone].

PMID- 16279653
TI  - [Anabolic and catabolic action of PTH].

PMID- 16279654
TI  - [Acceleration of bone formation].

PMID- 16279655
TI  - [Action of parathyroid hormone on the kidney].

PMID- 16279656
TI  - [Primary hyperparathyroidism].

PMID- 16279657
TI  - [Familial hypoparathyroidism].

PMID- 16279658
TI  - [Familial hypocalciuric hypercalcemia].

PMID- 16279659
TI  - [Secondary hyperparathyroidism].

PMID- 16279660
TI  - [Idiopathic hypoparathyroidism].

PMID- 16279661
TI  - [Pseudohypoparathyroidism].

PMID- 16279662
TI  - [Hypoparathyroidism].

PMID- 16279663
TI  - [Translational research on parathyroid hormone].

PMID- 16279664
TI  - [Perspective for development of parathyroid hormone and related compounds as
      therapeutic agents for osteoporosis].

PMID- 16279665
TI  - [PTHrP: gene, structure, biosynthesis, regulation of expression].

PMID- 16279666
TI  - [Physiological functions of parathyroid hormone-related peptide].

PMID- 16279667
TI  - [Parathyroid hormone-related peptide (PTHrP) gene recombinant mice].

PMID- 16279669
TI  - [Structure, expression profile and function of BMP].

PMID- 16279668
TI  - [Discovery of BMP (bone morphogenetic protein) and its significance in life
      science].

PMID- 16279670
TI  - [BMP receptors and signal transduction].

PMID- 16279671
TI  - [BMP antagonists].

PMID- 16279672
TI  - [Regulatory mechanism of bone morphogenetic protein gene expression].

PMID- 16279673
TI  - [BMP mutant animals].

PMID- 16279674
TI  - [Analysis of transgenic and knockout mice for BMP receptors].

PMID- 16279675
TI  - [Roles of BMP in chondrogenesis].

PMID- 16279676
TI  - [Stimulation of bone formation].

PMID- 16279677
TI  - [Roles of BMPs during endochondral bone formation].

PMID- 16279678
TI  - [Bone mass regulation].

PMID- 16279679
TI  - [Osteoporosis and bone morphogenetic protein (BMP)].

PMID- 16279680
TI  - [Osteosclerosis related with bone morphogenetic protein (BMP)].

PMID- 16279681
TI  - [Primary pulmonary hypertension].

PMID- 16279682
TI  - [Translational research using BMP family proteins].

PMID- 16279683
TI  - [Development of BMP-related drugs].

PMID- 16279684
TI  - [Fibroblast growth factor 23, a new phosphaturic factor in hypophosphatemic
      rickets/osteomalacia].

PMID- 16279685
TI  - [FGF: genes, structure, biosynthesis and function].

PMID- 16279686
TI  - [FGF receptor and FGF signaling pathways].

PMID- 16279687
TI  - [Regulation of fibroblast growth factor 23 in metabolic bone diseases].

PMID- 16279689
TI  - [Assay methods for FGF].

PMID- 16279688
TI  - [FGF-mutant mice].

PMID- 16279690
TI  - [Role of fibroblast growth factors (FGFs) in wound healing and regeneration].

PMID- 16279691
TI  - [Stimulation of fracture healing by FGFs].

PMID- 16279693
TI  - [Regulatory effect of FGF23 on phosphate and vitamin D metabolism].

PMID- 16279692
TI  - [Role of FGFs in osteogenesis and chondrogenesis].

PMID- 16279694
TI  - [Tumor-induced rickets/osteomalacia].

PMID- 16279695
TI  - [Autosomal dominant hypophosphatemic rickets/osteomalacia].

PMID- 16279696
TI  - [McCune-Albright syndrome].

PMID- 16279697
TI  - [FGF-23 in primary and secondary hyperparathyroidisms].

PMID- 16279698
TI  - [Translational research in FGFs].

PMID- 16279700
TI  - [Growth hormone (GH) gene, secretion, and biological activity].

PMID- 16279699
TI  - [Significance of GH as a regulator of bone metabolism].

PMID- 16279701
TI  - [GH receptor and its downstream signal transduction].

PMID- 16279702
TI  - [Senile osteoporosis].

PMID- 16279703
TI  - [Osteoporosis caused by pediatric diseases].

PMID- 16279704
TI  - [Osteopenia caused by growth hormone deficiency in childhood].

PMID- 16279705
TI  - [Chronic renal failure].

PMID- 16279706
TI  - [Fracture prevention and GH replacement therapy].

PMID- 16279707
TI  - [Growth disorders caused by mutations of GH-1 or GH receptor gene].

PMID- 16279708
TI  - [Osteopontin and regulation of bone metabolism].

PMID- 16279709
TI  - [Osteopontin-gene, structure and biosynthesis].

PMID- 16279710
TI  - [Osteopontin receptors and signal transduction].

PMID- 16279711
TI  - [Distribution and expression of osteopontin].

PMID- 16279712
TI  - [Regulation of osteopontin in vivo].

PMID- 16279713
TI  - [Osteopontin in rheumatoid arthritis].

PMID- 16279714
TI  - [Postmenopausal osteoporosis].

PMID- 16279715
TI  - [Osteopontin and atherosclerosis].

PMID- 16279716
TI  - [Osteopontin and its modulators].

PMID- 16279717
TI  - Deformation and flexural properties of denture base polymer reinforced with glass
      fiber sheet.
AB  - The purpose of this study was to investigate the deformation and flexural
      properties of acrylic and urethane polymers reinforced with glass fiber sheet.
      Four types of specimen--self-curing resin plate (R), light-curing oligomer plate
      containing a reinforcement (GO), and self-curing resin plate containing a
      reinforcement on one (GR) or both (GRG) sides--were prepared with three
      thicknesses: 1.5, 2.4, and 3.0 mm. Gaps between polymerized test specimen and a
      standard metal plate were measured at the corner (C), middle of the long sides
      (LS), and middle of the short sides (SS). The gaps for R were 0-2.0 microm. GO
      and GR markedly deformed at Points C, LS, and SS, and the degree of deformation
      increased as GO became thinner. Flexural strength was significantly increased by
      the reinforcement (p < 0.05). The flexural moduli of 3.0-mm thick R, GO, and GR
      were significantly smaller than that of 1.5-mm thick specimens.

PMID- 16279718
TI  - Effects of Ni2+ ions on cell viability and NO production of murine peritoneal
      exudate cells (macrophages) with and without lipopolysaccharide stimulation.
AB  - The purpose of this study was to clarify the cytotoxicity of Ni2+ ions against
      murine peritoneal exudate cells (PEC) (macrophages). First, we examined the cell
      viability of PEC with and without lipopolysaccharide (LPS) stimulation in culture
      media containing Ni2+ ions up to 1000 micromol/L. Results showed that the
      cytotoxicity of Ni2+ ions against PEC was dose-dependent and accelerated by LPS
      stimulation, especially in media with Ni2+ ions exceeding 100 micromol/L. Second,
      we measured the production of nitric oxide (NO) from PEC and found that LPS
      caused the PEC to produce abundant NO. However, high dose of Ni2+ ions at
      concentration more than 200 micromol/L hindered and inhibited NO production.
      These results pointed out that the cytotoxicity of Ni2+ ions against macrophages
      depended on both the Ni2+ ion concentration and the presence of bacteria with
      LPS. Further, NO--a killer of bacteria--was lost when LPS-stimulated macrophages
      were exposed to high dose of Ni2+ ions.

PMID- 16279719
TI  - Modified direct relining method produces an accurate adaptation of denture.
AB  - The purpose of this study was to examine if a modified direct relining method
      could result in excellent denture adaptation compared to a conventional method.
      Direct relining was done using heat-polymerized acrylic resin base on a maxillary
      cast with two times of three seconds of cooling using dichloro-difluoro-methane
      coolant. Discrepancy between cast and intaglio surface at residual ridge and
      center of palate was measured at 12 minutes after mixing of resin (Time 0) and at
      24 hours or seven days after water immersion (36 degrees C). At Time 0 (with
      three seconds of cooling), the discrepancy at ridge (0.39 +/- 0.27) and palate
      (0.66 +/- 0.31) was significantly lower compared to that of control (ridge = 0.93
      +/- 0.51; palate = 1.14 +/- 0.13, P < 0.05); and the same observations occurred
      at 24 hours and seven days too. On intaglio side (with three seconds of cooling),
      the peak temperature was 5 degrees C lower than that of control and it occurred
      at a delay of about 60 seconds. Based on the results of this study, we therefore
      suggested that this delayed and lowered temperature served to improve the
      adaptability of denture base.

PMID- 16279720
TI  - Radiopacity of experimental composite resins containing radiopaque materials.
AB  - This study aimed to investigate the relationship between the radiopacity of an
      experimental light-cured composite resin and the amount and type of its
      radiopaque material: Ti, SrCO3, ZrO2, BaSO4, or Bi2O3. Radiopacity of each
      material was evaluated in terms of aluminum equivalent thickness using an
      aluminum step wedge. Then, the half-value layer thickness of the experimental
      composite resin, which had an aluminium equivalent thickness of 1 mm, was
      evaluated. It was found that the effects of elemental composition were not
      identical when evaluated in terms of aluminum equivalent thickness and by half
      value layer. Nevertheless, both measurement methods indicated that radiopacity
      increased with increase in radiopaque material content as well as increase in
      atomic number of the element.

PMID- 16279722
TI  - Fracture toughness measurement of dental ceramics using the indentation fracture
      method with different formulas.
AB  - This study examined fracture toughness (KIC) measurements obtained using the
      indentation fracture (IF) method with a view to improving their reliability. The
      KIC values of five dental ceramics were measured using the IF method with five
      different formulas, and the single-edge precracked beam (SEPB) method was used as
      a control. The elastic moduli of the dental ceramics were evaluated by dynamic
      hardness test. Load conditions of the dental ceramics that produced a
      median/radial crack for the IF method formulas were investigated. Based on the
      resultant c/a and P/c1.5 values, the indentation load (P) required for
      median/radial crack occurrence varied greatly from 29.4 to 196 N depending on the
      ceramic used. Among the five formulas, none of the KIC values obtained by the IF
      method with Miyoshi's formula differed significantly (p > 0.05) from the values
      obtained using SEPB method. These results suggested that, after an appropriate
      indentation load is determined, reliable KIC values for small dental ceramic
      specimens can be easily obtained using the IF method if Miyoshi's formula is used
      in combination with the dynamic hardness test.

PMID- 16279721
TI  - Clinical evaluation of a polyacid-modified resin composite in class V carious
      lesions: 3-year results.
AB  - This study evaluated the three-year clinical performance of Class V restorations
      made of a polyacid-modified resin composite, Dyract. Ninety-two Class V carious
      lesions in 28 patients were restored with Dyract. Restorations were clinically
      evaluated at baseline, first, second, and third year recall visits, according to
      the modified Ryge criteria by two experienced, calibrated examiners. Retention
      rate after three years in Class V carious restorations was 92.4%, with only seven
      failed restorations. Color change and marginal discoloration in restorations were
      found to be statistically significant (p = 0.013 and p < 0.001, respectively) at
      the end of third year, but none of the affected restorations required
      replacement. The results of this study revealed that at the end of three years,
      Dyract exhibited good clinical success rate but significant color change and
      marginal discoloration in Class V carious lesions.

PMID- 16279723
TI  - Adhesive properties and kinetic polymerization behavior of resins containing
      adhesion promoting monomers for precious metals.
AB  - Adhesion promoting monomers -5-(4-vinylbenzyl)-2-thiobarbituric acid (5VS), 9,10
      epithiodecyl methacrylate (EP8MA), 9,10-epithiodecyl 4-vinylbenzoate (EP8VB), and
      3,4-epithiobutyl 2,2-bis(methacryloyloxymethyl)propionate (EP2BMA)--were added to
      the MMA liquid of a MMA-PMMA/TBBO resin. Three dental precious metal alloys were
      butt-jointed together with the MMA-PMMA/TBBO adhesive resin, and tensile bond
      strength was measured after 2,000 thermocycles in water. Polymerization kinetics
      of MMA by 2,2'-azobis (isobutyronitrile) at 70 degrees C in the presence of 5VS,
      EP8MA, EP8VB, or EP2BMA were examined quantitatively using a DSC to clarify the
      relationship between the adhesive properties of MMA-PMMA/TBBO adhesive resin and
      the kinetic polymerization behavior thereof. Obtained kinetic parameters
      indicated that 5VS was not suitable as an adhesive monomer for adhesive resin
      formulations and that EP2BMA possessed the latent potential as an adhesive
      monomer. Further, tensile test results revealed the applicability of EP8MA,
      EP8VB, and EP2BMA as an adhesive monomer component of adhesive resin
      formulations.

PMID- 16279724
TI  - In vitro color stability of provisional crown and bridge restoration materials.
AB  - Discoloration of provisional restorations can be an esthetic problem, especially
      when the treatment plan requires long-term provisionalization. In this study,
      therefore, we examined the effects of staining solution on the color stability of
      these provisional crown and bridge restoration materials: Structur, Temdent, and
      Tab 2000. Treatment solutions were namely carrot juice, tea, cola, light cola,
      and distilled water. Thirty samples were prepared for each type of provisional
      material, such that a total of 90 samples were prepared. The color value of each
      sample was measured with a colorimeter at baseline and after one day, one week,
      two weeks, and four weeks of immersion in various treatment solutions. Results
      were determined using the CIELAB system. Color change data were calculated and
      subjected to two-way analysis of variance. To examine significant interactions,
      one-way ANOVA and Tukey's multiple comparisons test were performed to identify
      differences between the solutions (p < or = 0.05). After four weeks of treatment,
      color difference values were found to range from 0.20 to 3.99 deltaE* units. The
      highest color difference values were obtained in carrot juice, cola, and tea with
      Structur samples after four weeks, where these values were categorized as
      "noticeable" and "unacceptable" color change values. Based on the results of this
      study, we do not recommend amine-containing Structur to be used as a provisional
      crown and bridge restorative material for treatments of a longer duration.

PMID- 16279725
TI  - New evaluation method by microfocus radiograph CT for 3D assessment of internal
      adaptation of all-ceramic crowns.
AB  - The aim of this study was to evaluate the effectiveness of the microfocus
      radiograph CT system in examining the adaptation of all-ceramic crowns three
      dimensionally and non-destructively. The computed tomograms of the crown and
      abutment model were filmed by microfocus radiograph CT. Using a volumetric
      rendering software, images of gaps were extracted and reconstructed three
      dimensionally, and their volume data analyzed. In order to compare this method
      with the conventional method, fitness test silicone paste was sandwiched between
      the abutment and all-ceramic crown. Adaptation of the crown on the abutment model
      was then observed non-destructively and three-dimensionally. Furthermore, the
      gaps could be analyzed in any arbitrary position. Concerning mean gap thickness,
      there was significant differences between the two measurement methods. However,
      it was very slight. We therefore concluded that the microfocus radiograph CT
      system is well positioned to be an extremely effective method in examining the
      adaptation of all-ceramic crowns.

PMID- 16279726
TI  - Effect of material and configuration of antagonist on combined wear.
AB  - The aim of this study was to investigate the effect of antagonist material and
      configuration on combined wear, which was produced by alternating toothbrush wear
      and simulated occlusal wear on one specimen. Worn volume and maximum worn depth
      comparisons were done using two antagonist materials (steel and ceramic) and two
      antagonist configurations (flat and round). For the material factor, worn volume
      by the ceramic antagonist was greater than that by steel antagonist in the
      combined wear test. For the configuration factor, the round ceramic antagonist
      induced a greater volume loss of the resin composite. As for maximum worn depth,
      both the material and configuration of antagonist were influencing factors in the
      combined wear test--where the round ceramic antagonist induced a deeper wear of
      the resin composite. Based on the results of this study, we concluded that a
      round ceramic antagonist is suitable to be used for evaluating the wear behavior
      of resin composites.

PMID- 16279727
TI  - Properties of an indirect composite material polymerized with two different
      laboratory polymerizing systems.
AB  - The purpose of the current study was to evaluate the performance of two
      laboratory light polymerization systems used to polymerize an indirect composite
      (Sinfony). A two-step polymerization system (Visio-Alfa and Beta) and a halogen
      metal halide unit (Twinkle MIII) were assessed. The composite was polymerized
      either with the Visio units or with the MIII unit for different exposure periods.
      Knoop hardness, water sorption, and solubility in water of the composite
      polymerized with the following modes were determined: Visio, 15 minutes; MIII,
      30, 60, 90, 120, and 180 seconds. Extension of light exposure time to the MIII
      unit improved the hardness of the composite from 30.5 (30 s) to 40.7 (180 s),
      whereas hardness obtained with the Visio units resulted in 24.8 (15 minutes).
      Water sorption and solubility of the composite were greater when it was
      polymerized with the Visio units than with the MIII unit.

PMID- 16279728
TI  - Color stability of a dental composite after immersion in various media.
AB  - The purpose of this study was to determine the effects of staining solutions on
      the different shades of a dental composite, and to compare these effects with
      that of distilled water. Two shades of effect (ET1 and ET2), two shades of enamel
      (EL and EM), and two shades of dentin (DA1 and DA2) were used. Specimens were
      immersed in three staining solutions (chlorhexidine gluconate, filtered coffee,
      and orange juice) and distilled water. Color changes were characterized using the
      CIELAB color space. Since significant interactions occurred, the staining effect
      of each solution on each shade was determined using one-way ANOVA and the levels
      of factor in one-way ANOVA were compared using Tukey's method (p < or = 0.05).
      The staining solutions were found to be more chromogenic than distilled water,
      and EM and DA2 shades were found to be more color-stable. Based on the color
      change results in this study, chlorhexidine gluconate (1.45), filtered coffee
      (1.43), and orange juice (1.02) were determined as having "slight" staining
      effects on the tested shades. As for the tested shades in this study, they
      revealed acceptable color change results.

PMID- 16279729
TI  - Effect of heat history on the corrosion of ferritic stainless steels used for
      dental magnetic attachments.
AB  - This study investigated the effect of heat history on the corrosion of keepers
      used for dental magnetic attachments. Ferritic stainless steels of SUS 444 and
      447J1 were prepared with heat treatments in the temperature range of 550-850
      degrees C for 1-5 hours. The stainless steels were electrochemically and
      metallurgically examined by anodic polarization curves in a 0.9% NaCl solution
      and by microstructural observation using an electron probe microanalyzer with
      WDS. Heating both kinds of stainless steel at 650-750 degrees C for two hours or
      more led to the deterioration of their corrosion resistance. For example, there
      was evidence of a reduction in the breakdown potentials and an increase in the
      current densities of the anodic polarization curves. These phenomena were
      attributed mainly to the precipitation of the sigma (FeCr) or chi (Fe18Cr6Mo5)
      phase, which sometimes resulted in intergranular corrosion. When dental alloys
      are cast in investment molds embedding the keepers, the heat time required for
      thermal expansion of the molds should be kept under one hour.

PMID- 16279730
TI  - In vivo effect of fluoride-substituted apatite on rat bone.
AB  - Different types of calcium phosphate compounds are commercially available for
      medical and dental applications as bone substitute materials. Biological apatites
      contain several kinds of minor elements such as carbonate (CO3), magnesium (Mg),
      and fluoride (F) in enamel, dentin, and bone. It has been shown that F ion and F
      substituted apatite promoted osteoblast proliferation and inhibited osteoclast
      cell activity. The purpose of this study was to investigate the in vivo rat tibia
      activity on F-substituted apatite (FAp). Apatites of unsintered calcium deficient
      apatite (CDA), and FAps, with low, medium, and high F concentrations, were
      implanted in rat tibia for 1 and 2 weeks. Implanted tissues were embedded in
      paraffin blocks, stained with hematoxylin-eosin and histomorphometrically
      observed. Results showed that low F concentration induced better and faster new
      bone formation in vivo compared to CDA. Therefore the results suggested that F as
      a minor element in bone rendered a suitable effect on bone formation in vivo.

PMID- 16279731
TI  - Effect of base monomer's refractive index on curing depth and polymerization
      conversion of photo-cured resin composites.
AB  - In this study, we examined the effect of the transmitted amount of visible light
      through a resin composite on the curing depth and polymerization conversion.
      Transmitted amount of visible light was strongly dependent on the magnitude of
      refractive index difference that existed between the resin and silica filler.
      More specifically, the differences arose from the type of base monomer used. The
      transmitted amount of visible light exhibited a good correlation with the curing
      depth and Knoop hardness ratio of the bottom surface against the top surface of
      the resin composite. To improve the polymerization conversion of the cavity
      floor, it is important to reduce the refractive index difference that exists
      between the base resin and silica filler.

PMID- 16279732
TI  - Surface composition and texture of titanium polished with colloidal silica
      suspension and chromic oxide slurry.
AB  - CP titanium was polished with a colloidal silica suspension and chromic oxide
      slurry under low and high pressures. The polished surfaces were characterized by
      means of EPMA and XPS. Irrespective of polishing pressure, colloidal silica
      suspension successfully created a mirror-like surface that was clean at EPMA
      level. However, XPS detected a small amount of silicon on the outermost surface.
      On the other hand, chromic oxide slurry under high pressure yielded a very uneven
      surface with numerous scratches. The EPMA and XPS results suggested the presence
      of chromium-containing species in the polished surface, which might include
      hydroxides as well as oxides. In addition, the level of oxygen concentration was
      noticeably raised, which probably resulted from the increase of surface oxide
      film thickness or the extension of oxide-to-metal transition zone.

PMID- 16279733
TI  - PBS buffer solutions with different pH values can change porosity of DNA-chitosan
      complexes.
AB  - We examined the effect of phosphate-buffered saline (PBS) solution with different
      pH values on the formation of porosity in the DNA/chitosan complexes, and
      evaluated the intercalation behavior of the complexes. Four different PBS
      solutions with pH = 6.0, 7.0, 7.4, and 7.8 were used for rinsing water-insoluble
      DNA-chitosan complexes. All complexes showed high porosities ranging from 83 to
      95%. Rinsing with PBS at pH 7.0, 7.4, and 7.8 reduced the porosity of the DNA
      chitosan complexes. Re-rinsing with PBS at pH 7.4 reduced the porosity of the DNA
      chitosan complex rinsed with PBS at pH 6.0. The appearances for porous formation
      were influenced by the differences in pH of PBS. Daunorubicin hydrochloride
      intercalated and bound in the grooves of DNA within all of the DNA-chitosan
      complexes, indicating that DNA in the complexes maintained its double-stranded
      helical structure. These results suggested that PBS-rinsed DNA-chitosan complex
      is promising as a scaffold material in tissue engineering.

PMID- 16279735
TI  - Color and translucency of resin composites for layering techniques.
AB  - The purpose of this study was to evaluate the colors of resin composites used for
      the layering technique, as well as the translucency at various thickness. For the
      purpose of calculating the translucency parameter (TP), black and white backings
      were used to evaluate the CIELAB parameters of Filtek Supreme (3M) and Gradia
      Direct (GC) disks of various thicknesses (0.5, 1.0, 2.0, 3.0 and 4.0 mm) and of
      three different shades (enamel-shade, body-shade, and opaque-shade). As for the
      color of each shade, it was evaluated using 4mm thick specimens on the white
      backing. Regarding TP, the opaque-shades were less translucent than the other
      shades. It was also found that translucency increased exponentially as thickness
      was reduced--regardless of shade. Regarding color, enamel-shades were more bluish
      (especially in GD) compared to the other shades, and the opaque-shades displayed
      a brighter and yellowish characteristic. In the layering technique, it is
      fundamental to have an accurate knowledge about the translucency and colors of
      the materials/shades used.

PMID- 16279734
TI  - In vitro corrosion of dental Ag-based alloys in polyvinylpyrrolidone iodine
      solution.
AB  - The corrosion and tarnish behaviors of three Ag-based alloys (Ag-Pd-Cu-Au alloy,
      Ag-In alloy, and Ag-Sn-Zn alloy) in polyvinylpyrrolidone iodine (povidone-iodine)
      solution were examined. The degree of tarnish was evaluated by visible-ray
      spectrocolorimetry. Corrosion potential measurements and analyses of corrosion
      products by X-ray diffractometry were carried out to elucidate the corrosion
      mechanism. The corrosion rate of the three Ag-based alloys in povidone-iodine
      solution at its practical concentration used as a gargle solution was so fast
      that the alloys tarnished within 10 seconds of immersion with the formation of
      AgI. Thermodynamic consideration and the results of surface analysis by X-ray
      diffractometry revealed that the main anodic and cathodic reactions were Ag + I(
      )-->AgI + e- and I2 + 2e(-)-->2I- respectively.

PMID- 16279736
TI  - Mechanical properties of an experimental soft lining material based on urethane
      oligomer.
AB  - The purpose of this study was to investigate the apparent viscosities and
      mechanical properties of two experimental light-curing soft lining materials (SLM
      1 and SLM-2) based on soft-type urethane oligomers, as well as the shear bond
      strength and dye penetration between the denture base resin and the polymerized
      SLMs after storage in water. The apparent viscosities of SLM-1 and SLM-2 were
      144.0-146.9 and 1.9 Pa x s respectively. After storage in water for two
      prescribed periods (one day and three months), the mechanical properties of the
      SLMs on the overall were 10.6-20.6 MPa for elastic modulus, 69.3-72.1 for
      hardness, and 3.8-4.0 MPa for adhesive strength. Tensile strength was observed to
      decrease after three months' storage in water, when compared to that after one
      day storage (p < 0.01). Water sorption rates also differed significantly (p <
      0.05)--namely 3.0 and 2.8 mg/cm2 for SLM-1 after one day and three months
      respectively, and 2.0 and 2.2 mg/cm2 for SLM-2. As for dye penetration, no
      infiltration was observed at the denture base resin-SLM interface after three
      months' storage. Based on the results of this study, it seemed like the SLMs
      possess many suitable properties for use with a new technique that we recently
      developed for preparing denture base resin and soft lining material.

PMID- 16279737
TI  - Twenty-four hour bond strength between layers of a highly loaded indirect
      composite.
AB  - This study evaluated the repair bond strength of Estenia composite. Disk
      specimens of a dentin material were conditioned with varying combinations of
      silane primer (Add-on Primer, Clearfil Porcelain Bond Activator, Clearfil
      Porcelain Bond Activator + Clearfil Mega Bond-Primer, Porcelain Liner M, and
      unprimed) and bonding agent (Clearfil Mega Bond-Bond, Modeling Liquid, Stain
      Diluent, and no bonding agent). After photopolymerization of the enamel material
      placed on each surface, the specimens were either wet- or dry-stored at 37
      degrees C for 24 hours. Average shear bond strength varied from 24.9 to 61.4 MPa,
      where the Clearfil Porcelain Bond Activator + Clearfil Mega Bond-Bond group and
      the Add-on Primer + Modeling Liquid group showed the greatest bond strength for
      dry and wet conditions respectively. To achieve reliable bond strength between
      layers of Estenia composite, it is highly recommended to use specific
      combinations of silane primer and bonding agent.

PMID- 16279738
TI  - Study of finite element modeling from CT images.
AB  - The use of finite element analysis is becoming more widespread with rapid
      advancements in computer technology. However, the field of dentistry is not
      enjoying the spillover benefits of the expanded use of this design simulation and
      analysis tool. Finite element modeling requires measurement of the object.
      However, as the living body is morphologically very complex, this requires a
      great deal of both time and skill using CAD applications, thus preventing its
      widespread adoption in the dental field. Although there have been reports of
      finite element modeling from CT images, these methods require skilled programmers
      for software development--which is another factor that prevents its widespread
      adoption in dentistry. Therefore, establishing a finite element modeling method
      that is both accurate and practical will be of great benefit in clinical
      dentistry. In the present study, a method using computer tomography and existing
      software was examined for finite element model construction based on computer
      tomography images. The results suggested that the method developed here is
      feasible and practical for clinical use.

PMID- 16279739
TI  - In vitro study on marginal and internal fit of CAD/CAM all-ceramic crowns.
AB  - The purpose of this study was to evaluate the marginal and internal fit of all
      ceramic crowns fabricated using the Decsy CAD/CAM system. A master die of
      maxillary first premolar was measured, and experimental crowns were fabricated.
      Four conditions were established by combining two convergence angles (4 degrees
      and 12 degrees) of the abutment with two different luting space settings (15
      microm and 55 microm). The results showed that the experimental crowns had a
      marginal gap of 42 to 56 microm. When the luting space setting was 15 microm, the
      internal gap was 85-88 microm; when the setting was 55 microm, the internal gap
      was 126-138 microm. The marginal gap for each experimental crown met the
      clinically acceptable criterion.

PMID- 16279740
TI  - SEM observation of collagen fibrils secreted from the body surface of osteoblasts
      on a CO3apatite-collagen sponge.
AB  - The secretion of collagen by osteoblasts was observed by scanning electron
      microscopy (SEM). Osteoblast-like cells were cultured on a CO3apatite-collagen
      sponge reinforced with a porous HAp frame. After three days' incubation, a number
      of newly created matrix fibrils, forming a network structure, were observed at
      the cell surface. SEM also showed that osteoblasts secreted collagen fibrils from
      their membrane, and that the collagen fibrils were twisted together. When
      collagen in an aqueous sol solution was sprayed onto the extremely smooth surface
      of a mica plate to support the secretion of osteoblasts, a collagen network
      structure could be clearly observed with atomic force microscopy (AFM). With this
      in vitro phenomenon, we could confirm the formation of collagen network structure
      without biological function. Therefore, it was suggested that the CO3apatite
      collagen sponge used in this study is a favorable scaffold biomaterial, on which
      osteoblasts could produce the unmistakable, characteristic extracellular matrix
      for mineralization. For therapeutic use of hard tissue biomaterials, collagen
      formation as an extracellular matrix (ECM) is very important because
      mineralization is subsequent to ECM.

PMID- 16279741
TI  - When should we suspect osteoporosis in patients with chronic airways disease?

PMID- 16279742
TI  - Depression and COPD: is smoking a link?

PMID- 16279744
TI  - Increased risk of depression in COPD patients with higher education and income.
AB  - This study examined potential modifying effects of income and education on the
      relationship between chronic obstructive pulmonary disease (COPD) and depression.
      The analysis was based on 44,963 Canadians aged 35 years or more who participated
      in the Canadian National Population Health Survey in 1996-1997. Logistic
      regression analysis was used to examine the association between prevalence of
      depression and COPD according to sex, income adequacy or educational level. We
      used a bootstrap procedure to take sampling weights and design effects into
      account. People with COPD had twice the prevalence of depression compared to
      those without COPD. The association tended to be stronger in well-educated men
      [adjusted odds ratio (OR) = 3.02, 95% confidence interval (CI) = 1.04, 8.75] and
      women (OR = 2.60, 95% CI = 1.55, 4.38) than those less educated (men: OR= 1.19,
      95% CI = 0.47, 3.05; women: OR = 1.93, 95% CI = 0.96, 3.87). An increased
      prevalence of depression associated with COPD was also found in women with higher
      household income (adjusted odds ratio = 4.57, 95% CI = 2.27, 9.19) than those
      with lower income. However, this pattern was not found in men. In conclusion,
      COPD patients with higher education are more likely to be depressed. The
      modifying effect of income may vary by gender. Possible reasons for these
      findings are explored.

PMID- 16279743
TI  - Osteoporosis screening in people with airways disease.
AB  - We tested associations between risk factors and bone mineral density in airways
      disease subjects, and developed a clinical screening tool to identify people who
      could benefit from bone mineral density testing. Subjects were recruited through
      hospital outpatients and pharmacies (Newcastle, n = 172). With survey refinement,
      we then tested a revised tool in a second sample (Adelaide, n = 317). Study
      factors included oral/inhaled corticosteroid use, asthma severity, respiratory
      admissions, physical activity, percent predicted forced expiratory volume in one
      second (FEV1), body mass index, and smoking history. Outcomes were bone mineral
      density of lumbar vertebra (L2-4) and total (or neck of) femur. Analysis was
      logistic regression with generation of a simple screening algorithm based upon
      coefficients. Scoring algorithm risk factors for T-score of < - 2.0: age > or =
      68 = 10 points, bone mineral density < 20 = 25, weight < 60 kg = 20, 60-69 kg =
      10, > or = 80 cigarette pack years = 15, low-level leisure activity = 5, area
      under receiver operator curve 0.83. For a cut-off score of 10, sensitivity was
      91.2%, specificity 53.9%, positive and negative predictive values 52.3 and 91.7%,
      and 67.2% were correctly classified. In conclusions, our model has acceptable
      sensitivity, although limited specificity. Use of this tool may reduce
      unnecessary referrals for bone mineral density measurement.

PMID- 16279745
TI  - Physical and emotional aspects of self-reported health status: a two-factor model
      of the short-form Breathing Problems Questionnaire.
AB  - The short version of the Breathing Problems Questionnaire (BPQ) is used as an
      outcome tool in pulmonary assessment. The aim of the study was to establish the
      validity of scoring BPQ with two subscales, reflecting emotional and physical
      components of health-related quality of life (HRQoL). Two subscales were
      suggested by exploratory factor analysis conducted on a data set of 97 patients
      with chronic obstructive pulmonary disease (COPD). Both subscales were
      significantly associated with the 6 minute walk test, total quality of life, and
      emotional stability. Only the physical subscale was significantly associated with
      FEV1, and only the emotional subscale was significantly associated with
      happiness. Overall, the sizes of the different correlations are consistent with
      the conceptual differentiation of the two subscales. We suggest that evaluation
      of rehabilitation can be made with the two subscales as well as an overall score
      of the BPQ.

PMID- 16279746
TI  - Impact of long-term ventilation on patients' health status.
AB  - Therapy and rehabilitation of common causes of respiratory-induced disability are
      directed towards a reduction of exacerbations, minimization of symptom severity,
      and improvement, or at least maintenance, of the patient's health. Unfortunately,
      these diseases are frequently complicated by chronic respiratory failure (CRF),
      which determines a rapid increase in the impact of the disease on the patient's
      daily life and well-being. Under such circumstances, the effect of therapy on a
      patient's health status and well-being represents the most important subjective
      outcome of treatment. An adequate assessment of patient's quality of life can
      only be obtained from the patients themselves; that is, it requires direct
      measurement through the use of valid and reliable questionnaires, whether generic
      or disease-specific. The St George's Respiratory Questionnaire and the Maugeri
      Foundation Respiratory Failure Questionnaire have been shown to be applicable and
      reliable in patients on long-term ventilation.

PMID- 16279747
TI  - Nebulized antibiotic therapy: the evidence.
AB  - The main indications for nebulized antibiotic use are as maintenance therapy for
      patients with chronic Pseudomonas aeruginosa infection and in treatment protocols
      aimed at eradicating early P. aeruginosa infection. Daily nebulized antibiotic
      therapy has been used extensively in Europe for the last 25 years and recently in
      North America following the introduction of tobramycin solution for inhalation
      (TSI). The antibiotic is delivered directly to the site of infection, maximizing
      its efficacy and reducing its potential for toxicity. The efficacy of nebulized
      antibiotic therapy has been confirmed by meta-analyses of early studies which
      usually involved only small numbers of patients, and recently by large scale
      randomized control trials. These studies have shown that regular aerosolized
      antibiotic treatment results in improved respiratory function, less hospital
      admissions and respiratory exacerbations, and a significant reduction in the load
      of P. aeruginosa respiratory tract infection. Concerns about increasing bacterial
      resistance do not yet seem to have had any clinical impact. Successful
      eradication of early P. aeruginosa infection has been reported with nebulized
      colistin (in combination with oral ciprofloxacin), tobramycin and TSI. No
      advantage has been shown in studies comparing nebulized and intravenous
      antibiotics versus intravenous antibiotics alone in the treatment of acute
      respiratory exacerbations. Inhalation of antibiotics may provoke bronchospasm and
      patients should be assessed before and after treatment prior to continuing long
      term therapy at home.

PMID- 16279748
TI  - Inpatient pulmonary rehabilitation: does it make sense?
AB  - Among the nonpharmacological therapies, pulmonary rehabilitation (PR) is
      particularly appropriate for patients with chronic respiratory impairment who,
      despite any optimal drug management, are still symptomatic and experience
      restriction in every day activities. Pulmonary rehabilitation performed in
      inpatient, outpatient, or home settings demonstrates short- and long-term
      clinical efficacy. Although disease severity does not inherently dictate
      candidacy for exercise training, the degree of physiological and functional
      impairment may influence setting in which the training should occur. Therefore,
      inpatient rehabilitation is generally best-suited for the most sick and most
      disabled patients. The overall results from the literature confirm that the
      inpatient setting for a PR program is a feasible option and does not necessarily
      result in higher direct costs when balanced against duration and effectiveness in
      terms of improved outcomes.

PMID- 16279749
TI  - Improving the sampling technique of arterialized capillary samples to obtain more
      accurate PaO2 measurements.
AB  - Arterialized earlobe capillary blood samples (ELCS) have been used as a
      measurement of blood gas status for over 20 years. There is general acceptance
      that there is a strong correlation and limits of agreement between arterial and
      arterialized blood samples with respect to pH and PaCO2. Although the correlation
      between the arterial and arterialized PaO2 is good, the limits of agreement poor.
      Our aim was to improve the accuracy of this technique in the measurement of PaO2
      by simultaneously monitoring the oxygen saturation by pulse oximetry whilst
      taking an ELCS. We hypothesize that significant discrepancies between the SaO2
      and SpO2 highlight either a poorly arterialized sample or an over aerated sample
      from air bubbles. We compared the SpO2 with the SaO2 of an arterial sample from
      27 inpatients. We used the limits of agreement between these samples to define
      the degree of discordance we would accept between SaO2 and SpO2 before repeat
      ELCS. Subsequently, 252 consecutive patients attending our respiratory physiology
      unit over a six-month period had an ELCS and simultaneous SpO2. If there was a
      discrepancy between SaO2 and SpO2 of > 2% the ELCS was repeated. There was a good
      correlation and limits of agreement between the SpO2 and arterial SaO2 (r = 0.97,
      mean difference +/- 95% limits of agreement: 0.34 +/- 2.68). A difference of more
      than 2% between arterialized SaO2 and SpO2 was identified in 21 patients out of
      252 (8.3%) with SaO2 higher in two and lower in 19 (r = 0.96, mean difference +/-
      95% limits of agreement: 0.66 +/- 3.1). Repeat ELCS of these 21 samples reduced
      this discrepancy improving the concordance of the measurements (r = 0.98, mean
      difference +/- 95% limits of agreement: 0.47 +/- 1.0). In one case a difference
      of 3% remained between the saturations. We conclude that the addition of
      simultaneous pulse oximetry with ELCS will identify rogue measurements in about
      8% of cases highlighting the need for repeat samples and thus increasing the
      accuracy of the measurement of PaO2 by ELCS.

PMID- 16279750
TI  - Measurement of dyspnoea is measuring what?

PMID- 16279752
TI  - Mortgaging the future: dumping ethics with nuclear waste.
AB  - On August 22, 2005 the U.S. Environmental Protection Agency issued proposed new
      regulations for radiation releases from the planned permanent U.S. nuclear-waste
      repository in Yucca Mountain, Nevada. The goal of the new standards is to provide
      public-health protection for the next million years - even though everyone admits
      that the radioactive wastes will leak. Regulations now guarantee individual and
      equal protection against all radiation exposures above the legal limit. Instead
      E.P.A. recommended different radiation exposure-limits for different time
      periods. It also recommended using only the arithmetic mean of the dose
      distribution, to assess regulatory compliance during one time period, but using
      only the median dose to assess compliance during another period. This piece
      argues that these two changes - in exposure-limits and in methods of assessing
      regulatory compliance - have at least four disturbing consequences. The changes
      would threaten equal protection, ignore the needs of the most vulnerable, allow
      many fatal exposures, and sanction scientifically flawed dose calculations.

PMID- 16279751
TI  - The complexity of competing and conflicting interests.

PMID- 16279753
TI  - Nanoethics: from utopian dreams and apocalyptic nightmares towards a more
      balanced view.
AB  - Nanotechnology is a swiftly developing field of technology that is believed to
      have the potential of great upsides and excessive downsides. In the ethical
      debate there has been a strong tendency to strongly focus on either the first or
      the latter. As a consequence ethical assessments of nanotechnology tend to
      radically diverge. Optimistic visionaries predict truly utopian states of
      affairs. Pessimistic thinkers present all manner of apocalyptic visions. Whereas
      the utopian views follow from one-sidedly focusing on the potential benefits of
      nanotechnology, the apocalyptic perspectives result from giving exclusive
      attention to possible worst-case scenarios. These radically opposing evaluations
      hold the risk of conflicts and unwanted backlashes. Furthermore, many of these
      drastic views are based on simplified and outdated visions of a nanotechnology
      dominated by self-replicating assemblers and nanomachines. Hence, the present
      state of the ethical debate on nanotechnology calls for the development of more
      balanced and better-informed assessments. As a first step in this direction this
      contribution presents a new method of framing the ethical debate on
      nanotechnology. Thus, the focus of this paper is on methodology, not on normative
      analysis.

PMID- 16279754
TI  - Emotional engagement in professional ethics.
AB  - Recent results from two different studies show evidence of strong emotional
      engagement in moral dilemmas that require personal involvement or ethical
      problems that involve significant inter-personal issues. This empirical evidence
      for a connection between emotional engagement and moral or ethical choices is
      interesting because it is related to a fundamental survival mechanism rooted in
      human evolution. The results lead one to question when and how emotional
      engagement might occur in a professional ethical situation. However, the studies
      employed static dilemmas or problems that offered only two choices whose outcome
      was certain or nearly so, whereas actual problems in professional ethics are
      dynamic and typically involve considerable uncertainty. The circumstances of
      three example cases suggest that increasing personal involvement and uncertainty
      could have been perceived as changes, threats, or opportunities and could
      therefore have elicited an emotional response as a way to ensure the reputation,
      integrity or success of oneself or a group to which one belongs. Such emotional
      engagement is only suggested and more studies and experiments are required to
      better characterize the role of emotional engagement in professional ethics.

PMID- 16279755
TI  - Attitudes of academic and clinical researchers toward financial ties in research:
      a systematic review.
AB  - Involvement of industry in academic research is widespread and associated with
      favorable outcomes for industry. The objective of this study was to review
      empirical data on the attitudes of researchers toward industry involvement and
      financial ties in research. A review of the literature for quantitative data from
      surveys on the attitudes of researchers to financial ties in research, reported
      in English, resulted in the 17 studies included. Review of these studies revealed
      that investigators are concerned about the impact of financial ties on choice of
      research topic, research conduct and publication, but this concern is less among
      investigators already involved with industry. Researchers approve of industry
      collaboration and financial ties when the ties are indirectly related to the
      research, disclosure is upfront, and results and ideas are freely publicized.
      However, their trust in disclosure as a way to manage conflicts may reveal a lack
      of awareness of the actual impact of financial incentives on themselves and other
      researchers.

PMID- 16279756
TI  - A call to restructure the drug development process: government over-regulation
      and non-innovative late stage (Phase III) clinical trials are major obstacles to
      advances in health care.
AB  - The history of drug/vaccine development has included major advances guided
      primarily by risk/benefit analyses concerning the innovative agent, not by
      evidence-based clinical trials (Phase I-IV). Because the approval for new drugs
      is hindered under the present process, the system requires restructuring. The
      Phase I/II study period should be more flexible, using the "environment of
      knowledge" about the new agent, plus risk/benefit assessments. Phase III, as
      presently constructed, does not add new adverse events data, it provides a
      narrower profile of drug efficacy than properly done Phase II studies, and
      placebo-controlled trials continue to raise unresolved ethical and social issues.
      Phase III studies should be abandoned for most drugs, and substituted with
      properly powered Phase II dose-ranging studies plus careful post-marketing
      surveillance. Phase III should be a penalty for poor drug development, not a
      regulatory requirement. To accomplish efficient drug development, greater
      cooperation between pharmaceutical companies and governments in developing
      clinical trials is needed rather than over-regulation. These changes will
      synchronize the drug development and regulatory process with the current rapid
      drug discovery process, reduce drug development time and cost, and improve
      patient care.

PMID- 16279758
TI  - Using electronic discussion boards to teach responsible conduct of research.
AB  - This study presents the results of a survey of student satisfaction with
      electronic discussion boards in a course on the responsible conduct of research
      (RCR). On a 1-5 scale, the respondents stated that the use of the electronic
      discussion board was an effective teaching tool (4.71), that it enabled them to
      get feedback from their peers (4.43), that it helped promote discussion and
      debate (4.36), that it helped them learn how to analyze ethical dilemmas in
      research (4.36), and that they would consider using an electronic discussion
      board, if they ever taught a course themselves (4.76). In their written comments,
      the respondents indicated that electronic discussion boards are a convenient way
      of promoting debate and in-depth discussion. These results suggest, but do not
      prove, that discussion boards can promote debate and discussion in courses on
      research ethics. Instructors who teach RCR should consider using electronic
      discussion boards in regular or online courses, and they should consider studying
      the effectiveness of electronic discussion boards in research ethics education.
      Although electronic discussion boards cannot replace the face-to-face interaction
      that occurs in a classroom setting, they may provide a useful medium for the
      exchange of ideas and opinions online.

PMID- 16279759
TI  - Introduction to a symposium: integrating ethics into engineering and science
      courses.

PMID- 16279757
TI  - The gap between law and ethics in human embryonic stem cell research: overcoming
      the effect of U.S. federal policy on research advances and public benefit.
AB  - Key ethical issues arise in association with the conduct of stem cell research by
      research institutions in the United States. These ethical issues, summarized in
      detail, receive no adequate translation into federal laws or regulations, also
      described in this article. U.S. Federal policy takes a passive approach to these
      ethical issues, translating them simply into limitations on taxpayer funding, and
      foregoes scientific and ethical leadership while protecting intellectual property
      interests through a laissez faire approach to stem cell patents and licenses.
      Those patents and licenses, far from being scientifically and ethically neutral
      in effect, virtually prohibit commercially sponsored research that could
      otherwise be a realistic alternative to the federal funding gap. The lack of
      federal funding and related data-sharing principles, combined with the effect of
      U.S. patent policy, the lack of key agency guidance, and the proliferation of
      divergent state laws arising from the lack of Federal leadership, significantly
      impede ethical stem cell research in the United States, without coherently
      supporting any consensus ethical vision. Research institutions must themselves
      implement steps, described in the article, to integrate addressing ethical review
      with the many legal compliance issues U.S. federal and state laws create.

PMID- 16279760
TI  - Ethics across the computer science curriculum: privacy modules in an introductory
      database course.
AB  - This paper describes the author's experience of infusing an introductory database
      course with privacy content, and the on-going project entitled Integrating Ethics
      Into the Database Curriculum, that evolved from that experience. The project,
      which has received funding from the National Science Foundation, involves the
      creation of a set of privacy modules that can be implemented systematically by
      database educators throughout the database design thread of an undergraduate
      course.

PMID- 16279761
TI  - Ethics in an operations management course.
AB  - Graduates of the management major at the University of Pittsburgh at Greensburg
      find employment in a variety of organizations. As future managers with employees
      from different professions, students expressed an interest in discussing ethics
      cases in the operations management class. The semester starts with students
      familiarizing themselves with various professional and corporate codes of ethics.
      Throughout the semester a number of short ethics' cases in operations' areas such
      as inventory management, scheduling, facility location, and product design are
      introduced to illustrate ethical issues that a manager and his/her employees
      might face. Students prepare individual responses before the in-class
      discussions. The semester ends with a long group ethics case discussion and
      formal case presentations. In the end-of-semester survey, students responded very
      favorably to an ethics component in the operations management class.

PMID- 16279762
TI  - Introducing ethics across the curriculum at South Dakota School of Mines and
      Technology.
AB  - This paper describes how the Electrical and Computer Engineering Department at
      South Dakota School of Mines and Technology has chosen to integrate ethics into
      their curriculum. All university freshmen engineering students are introduced to
      ethics through the presentation of ethical dilemmas. During this exercise,
      students are forced to argue both sides ('for' and 'against') of a hypothetical
      ethical engineering dilemma. It provides a setting for great discussion with the
      desired outcome that they learn to carefully analyze a situation before they draw
      conclusions. In the sophomore year, students are introduced to methods to use the
      fundamental principles, the fundamental canons, and the suggested guidelines for
      use with the fundamental canons of ethics when analyzing appropriate action to be
      taken when confronted with ethical dilemmas. We currently use the 'sophomore'
      method for seniors because the sequencing is just beginning. Next year the
      seniors will do more in-depth analysis of ethical case studies.

PMID- 16279763
TI  - Teaching ethical analysis in environmental management decisions: a process
      oriented approach.
AB  - The general public and environmental policy makers often perceive management
      actions of environmental managers as "science," when such actions are, in fact,
      value judgments about when to intervene in natural processes. The choice of
      action requires ethical as well as scientific analysis because managers must
      choose a normative outcome to direct their intervention. I examine a management
      case study involving prescribed burning of sagebrush (Artemisia tridentata)
      communities in south-central Montana (USA) to illustrate how to teach students to
      ethically evaluate a management action by precisely identifying: 1) the proposed
      management action, 2) the deficiency of the system to be remedied by the action,
      3) the stakeholders affected by the action, and 4) the category and type of
      values affirmed in the management action. Through such analysis, students are
      taught to recognize implicit and explicit value judgments associated with
      management actions, identify stakeholders to whom managers have legitimate
      ethical obligations, and practice a general method of ethical analysis applicable
      to many forms of environmental management.

PMID- 16279764
TI  - 7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)
      1,2,4-triazolo[4,3-b]pyridazine: a functionally selective gamma-aminobutyric
      acid(A) (GABA(A)) alpha2/alpha3-subtype selective agonist that exhibits potent
      anxiolytic activity but is not sedating in animal models.
AB  - There is increasing evidence that compounds with selectivity for gamma
      aminobutyric acid(A) (GABA(A)) alpha2- and/or alpha3-subtypes may retain the
      desirable anxiolytic activity of nonselective benzodiazepines but possess an
      improved side effect profile. Herein we describe a novel series of GABA(A)
      alpha2/alpha3 subtype-selective agonists leading to the identification of the
      development candidate 17, a nonsedating anxiolytic in preclinical animal assays.

PMID- 16279765
TI  - Synthesis and characterization of the novel fluorescent prolyl oligopeptidase
      inhibitor 4-fluoresceinthiocarbamoyl-6-aminocaproyl-L-prolyl-2(S)
      (hydroxyacetyl)pyrrolidine.
AB  - The synthesis and characterization of the first fluorescent prolyl oligopeptidase
      inhibitor 4-fluoresceinthiocarbamoyl-6-aminocaproyl-L-prolyl-2(S)
      (hydroxyacetyl)pyrrolidine is described. This compound has an IC50 value of 0.83
      nM and a dissociation half-life of 160 min, and its fluorescence signal is
      detectable using standard filters for fluorescein. These properties make this
      compound a suitable probe for visualizing prolyl oligopeptidase in various
      applications.

PMID- 16279766
TI  - Identification of novel and improved antimitotic agents derived from noscapine.
AB  - Analogues of the natural product noscapine were synthesized and their potential
      as antitumor agents evaluated. The discovery of a novel regioselective O
      demethylation facilitated the synthesis of the potent aniline 6, which arrests
      mammalian cells in the G2/M phase of the cell cycle at 0.1 microM and also
      affects tubulin polymerization. Aniline 6 is orally bioavailable and is 250-fold
      more potent than noscapine in reducing cell proliferation in rapidly dividing
      cells.

PMID- 16279767
TI  - SAR by MS: discovery of a new class of RNA-binding small molecules for the
      hepatitis C virus: internal ribosome entry site IIA subdomain.
AB  - A new class of small molecules that bind the HCV RNA IRES IIA subdomain with sub
      micromolar affinity is reported. The benzimidazole 'hit' 1 with a KD
      approximately 100 microM to a 29-mer RNA model of Domain IIA was identified from
      a 180000-member library using mass spectrometry-based screening methods. Further
      MS-assisted SAR (structure-activity relationships) studies afforded benzimidazole
      derivatives with sub-micromolar binding affinity for the IIA RNA construct. The
      optimized benzimidazoles demonstrated activity in a cellular replicon assay at
      concentrations comparable to their KD for the RNA target.

PMID- 16279768
TI  - SAR and 3D-QSAR studies on thiadiazolidinone derivatives: exploration of
      structural requirements for glycogen synthase kinase 3 inhibitors.
AB  - The 2,4-disubstituted thiadiazolidinones (TDZD) are described as the first ATP
      noncompetitive GSK-3 inhibitors. Following an SAR study about TDZD, different
      structural modifications in the heterocyclic ring aimed to test the influence of
      each heteroatom on the biological study are here reported here. Various compounds
      such as hydantoins, dithiazolidindiones, rhodanines, maleimides, and triazoles
      were synthesized and screened as GSK-3 inhibitors. After an extensive SAR study
      among these different heterocyclic families, TDZDs have been revealed as a
      privileged scaffold for the selective inhibition of GSK-3. A CoMFA analysis was
      also performed highlighting the molecular electrostatic field interaction in the
      interaction of TDZDs with GSK-3. Moreover, first mapping studies indicate two
      binding modes which in turn might imply relevant differences in the mechanism
      that underly the inhibitory activity of TDZDs.

PMID- 16279769
TI  - Synthesis, molecular modeling studies, and selective inhibitory activity against
      monoamine oxidase of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-(1H)- pyrazole
      derivatives.
AB  - A novel series of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-(1H)-pyrazole
      derivatives have been synthesized and investigated for the ability to inhibit
      selectively the activity of the A and B isoforms of monoamine oxidase (MAO). All
      the synthesized compounds show high activity against both the MAO-A and the MAO-B
      isoforms with Ki values between 27 and 4 nM and between 50 and 1.5 nM,
      respectively, except for a few derivatives whose inhibitory activity against MAO
      B was in the micromolar range. Knowing that stereochemistry may be an important
      modulator of biological activity, we performed the semipreparative
      chromatographic enantioseparation of the most potent, selective, and chiral
      compounds. The separated enantiomers were then submitted to in vitro biological
      evaluation. The selectivity of the (-)-(S)-1 enantiomer against MAO-B increases
      twice and a half, while the selectivity of the (-)-(S)-4 enantiomer against MAO-A
      triples. Both the MAO-A and MAO-B isoforms respectively of the 1O5W and 1GOS
      models deposited in the Protein Data Bank were considered in the computational
      study. The docking study was carried out using several computational approaches
      with the aim of proposing possible binding modes of the MAO enantioselective
      compounds 1 and 4.

PMID- 16279770
TI  - Novel tetralone-derived retinoic acid metabolism blocking agents: synthesis and
      in vitro evaluation with liver microsomal and MCF-7 CYP26A1 cell assays.
AB  - The potent inhibitory activity of novel 2-benzyltetralone and 2
      benzylidenetetralone derivatives vs liver microsomal retinoic acid metabolizing
      enzymes and a MCF-7 CYP26A1 cell assay is described. In the liver microsomal
      assay, the 2-biphenylmethyl-6-hydroxytetralone derivatives 16a and 16b were found
      to be potent inhibitors (IC50 = 0.5 and 0.8 microM) compared with the broad
      spectrum P450 inhibitor ketoconazole and the retinoid mimetic R115866 (IC50 =
      18.0 and 9.0 microM, respectively). In the MCF-7 CYP26A1 cell assay, the 2-(4
      hydroxybenzyl)-6-methoxytetralone 5 and unsaturated benzylidene precursor 6 were
      found to be the most potent (IC50 = 7 and 5 microM, respectively), which was
      comparable with liarozole (7 microM) but considerably less active than R115866
      (IC50 = 5 nM). With a CYP26A1 homology model, the tetralones were shown to be
      positioned in a hydrophobic tunnel with additional interactions, e.g., transition
      metal coordination and hydrogen-bonding interactions with GLY300, observed for
      the potent 4-hydroxyphenyl substituted inhibitors.

PMID- 16279771
TI  - [N-ethyl- and [N,N'-diethyl-1,2-bis(2,6-difluoro-3-hydroxyphenyl)
      ethylenediamine]dichloroplatinum(II): structure and cytotoxic/estrogenic activity
      in breast cancer cells.
AB  - N-Ethyl and N,N'-diethyl derivatives (erythro- and threo-2-PtCl2; meso- and D,L-3
      PtCl2) of [meso- and [D,L-1,2-bis(2,6-difluoro-3
      hydroxyphenyl)ethylenediamine]dichloroplatinum(II) (meso- and D,L-1-PtCl2) were
      synthesized and tested for cytotoxicity on the estrogen receptor-positive (ER+)
      human MCF-7 breast cancer cell line. In this test, only D,L-1-PtCl2 and threo-2
      PtCl2 showed strong cytotoxic properties. This revealed the existence of at least
      one NH2 fragment as a prerequisite for antitumor activity. Furthermore, studies
      on the three-dimensional structure of the new compounds demonstrated that the
      aryl and alkyl residues at the five-membered chelate ring have to be arranged in
      equatorial positions for the triggering of cytotoxic effects, very likely due to
      the reaction with d(GpG) sequences in DNA resulting in GG-N7,N7 chelates. A
      contribution of the ER-mediated processes--(a) hindrance of the cellular
      processing of Pt-modified DNA by overexpression of high mobility group domain
      proteins and (b) interruption of the vicious circle of mutual growth stimulation
      of breast cancer cells and granulocytes/macrophages by reduction of the formation
      of key cytokines--to the anti-breast cancer activity of threo-2-PtCl2 is
      unlikely, since we did not observe transcription activation in the test on ER+
      MCF-7 breast cancer cells stably transfected with luciferase reporter plasmid
      ERE(wtc)luc.

PMID- 16279772
TI  - Ligand docking in the gastric H+/K+-ATPase: homology modeling of reversible
      inhibitor binding sites.
AB  - Using the recent high-resolution X-ray structures determined for the Ca2+-ATPase,
      we have generated two homology models of the gastric H+/K+-ATPase reflecting the
      E1 and E2 conformations adopted by P-type ATPases in their catalytic cycle. In
      regimes where the in situ solid-state NMR-determined structure for 1,2,3
      trimethyl-8-(pentafluorophenylmethoxy)imidazo[1,2-a]pyridinium iodide (TMPFPIP),
      a reversible inhibitor of the gastric H+/K+-ATPase, was retained in its
      predefined conformation and was allowed full torsional flexibility in docking,
      the ligands localized to discrete binding volumes in the E1 model and to a single
      central binding space, together with secondary peripheral locations, in the E2
      conformation. The results of these binding studies are in good agreement with
      current site-directed mutagenesis data and support the suggestion that the
      binding site is proximal to the loop between TM5 and TM6 and TM8, the
      transmembrane (TM) region considered important for cation translocation.
      Furthermore, the results of the simulation with the flexible ligand complement
      the solid-state NMR structural constraints of this inhibitor when bound in situ
      to the protein.

PMID- 16279773
TI  - Specific targeting highly conserved residues in the HIV-1 reverse transcriptase
      primer grip region. Design, synthesis, and biological evaluation of novel,
      potent, and broad spectrum NNRTIs with antiviral activity.
AB  - Pyrrolobenzoxazepinones (PBOs) represent a new class of human immunodeficiency
      virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs)
      whose prototype is 5. Molecular modeling studies based on the X-ray structures of
      HIV-1 RT prompted the synthesis of novel analogues which were tested as anti-HIV
      agents. The PBO derivatives specifically designed to target the highly conserved
      amino acid residues within the beta12-beta13 hairpin, namely primer grip, proved
      to be very potent against the most common mutant enzymes, including the highly
      resistant K103N mutant strain. Structure-activity relationships (SARs) are
      discussed in terms of a possible interaction with the RT binding site, depending
      on the nature of the substituents at C-6. Among the pyrrolobenzoxazepines
      investigated, 15c appeared to be the most promising NNRTI of the series
      characterized by potent antiviral activity, broad spectrum, and low cytotoxicity.
      15c showed synergistic antiviral activity with AZT.

PMID- 16279774
TI  - Virtual screening of novel CB2 ligands using a comparative model of the human
      cannabinoid CB2 receptor.
AB  - To identify novel selective CB2 lead compounds, a comparative model of the CB2
      receptor was constructed using the high-resolution bovine rhodopsin X-ray
      structure as a template. The CB2 model was utilized both in building the database
      queries and in filtering the hit compounds by a docking and scoring method. In G
      protein activation assays, 1-isoquinolyl[3-(trifluoromethyl)phenyl]methanone (40,
      NRB 04079) was found to act as a selective agonist at the human CB2 receptor.

PMID- 16279776
TI  - Benzophenone-based farnesyltransferase inhibitors with high activity against
      Trypanosoma cruzi.
AB  - Less toxic drugs are needed to combat the human parasite Trypanosoma cruzi
      (Chagas's disease). One novel target for antitrypanosomal drug design is
      farnesyltransferase. Several farnesyltransferase inhibitors based on the
      benzophenone scaffold were assayed in vitro and in vivo with the parasite. The
      common structural feature of all inhibitors is an amino function which can be
      protonated. Best in vitro activity (LC50 values 1 and 10 nM, respectively) was
      recorded for the R-phenylalanine derivative 4a and for the N-propylpiperazinyl
      derivative 2f. These inhibitors showed no cytotoxicity to cells. When tested in
      vivo, the survival rates of infected animals receiving the inhibitors at 7 mg/kg
      body weight/day were 80 and 60% at day 115 postinfection, respectively.

PMID- 16279775
TI  - Synthesis and 3D QSAR of new pyrazolo[3,4-b]pyridines: potent and selective
      inhibitors of A1 adenosine receptors.
AB  - A number of 4-aminopyrazolo[3,4-b]pyridines 5-carboxylic acid esters (2-8) were
      synthesized and evaluated for their binding affinity at the A1, A2A, and A3
      adenosine receptors (AR), in bovine cortical membranes, as well as for their
      affinity toward human A1AR (hA1AR). Some of the new compounds were characterized
      by a high affinity and selectivity toward the A1 receptor subtype, showing a
      significant improvement in comparison with other pyrazolo-pyridines previously
      reported in the literature. In particular the methyl ester 2h as well as the
      isopropyl ester 5h, both of them bearing a p-methoxyphenylethylamino side chain
      at the position 4, presented Ki values of 6 and 7 nM, respectively. To
      rationalize the relationships between structure and affinity of the novel
      compounds, a 3D QSAR model was also generated starting from compounds belonging
      to different classes of known A1AR antagonists.

PMID- 16279777
TI  - In vitro anticancer activities and optical imaging of novel intercalative non
      cisplatin conjugates.
AB  - The first pi-conjugated macrocyclic diimine and triaza DNA-binding intercalators
      and their platinum(II) conjugates have been synthesized by direct Schiff base
      cyclocondensation. The in vitro anticancer activities of compounds 3, 4, and 5
      were tested on five cancer cell lines: MCF-7, A549, P388, A2780, and A2780cisR.
      Ovarian tumors were included specifically to evaluate the new conjugates' ability
      to circumvent A2780cisR resistance. Antitumor effects of the newly conjugated
      compounds were compared to those of cisplatin. The data clearly indicate that
      improved drug efficiencies are achieved as a result of the intercalative
      moieties. The luminescent probe that was integrated in complexes 8-10 made it
      possible to monitor drug penetration using optical imaging. Enhanced targeting of
      tumor nuclei by the study compounds was confirmed by confocal microscopy. This
      paper describes a new class of platinum-based antitumorals differing from
      cisplatin in several critical aspects with the potential for significantly
      improving clinical outcomes in cancer patients.

PMID- 16279778
TI  - Antitumor polycyclic acridines. 17. Synthesis and pharmaceutical profiles of
      pentacyclic acridinium salts designed to destabilize telomeric integrity.
AB  - Palladium(0)-mediated Suzuki-Miyaura and Heck transformations have been exploited
      to provide examples of 8-methylquino[4,3,2-kl]acridines and 8,13
      dimethylquino[4,3,2-kl]acridinium iodides bearing bulky saturated (3
      acetoxy)propyl or (E)-3-(morpholin-4-yl)-3-oxopropenyl substituents variously in
      the 3-, 6-, or 10-positions of the pentacyclic nucleus. The
      pharmacological/pharmaceutical properties of four compounds (4, RHPS4), (5,
      IH383), (6, RHPS16), and (17, RHPS19) were measured to assess their clinical
      potential as DNA G-quadruplex-stabilizing/telomerase inhibitory agents. The
      following properties were measured: stability in tissue culture media in the
      presence of A549 lung and MCF-7 breast tumor cells, metabolic stability when
      incubated with rat liver microsomes, and rate of uptake and subcellular location
      in A549 and MCF-7 cells. Compound 17 was unstable in tissue culture media, failed
      to achieve nuclear access, and was excluded from further consideration. Of the
      other agents, 4 exhibited the most favorable pharmaceutical profile: the agent
      has appropriate stability in the presence of tumor cells and rat liver microsomes
      and achieves rapid ingress into cell nuclei where the putative molecular target
      is located.

PMID- 16279779
TI  - Some insights into the stereochemistry of inhibition of macrophage migration
      inhibitory factor with 2-fluoro-p-hydroxycinnamate and its analogues from
      molecular dynamics simulations.
AB  - Macrophage migration inhibitory factor (MIF) exhibits tautomerase activity on
      phenylpyruvate and has E-stereochemistry preference. To investigate the binding
      modes of its competitive inhibitors and evaluate their binding affinities,
      molecular dynamics simulations together with MM-PBSA (molecular mechanics Poisson
      Boltzmann surface area) analysis were performed on MIF complexed with (E)-2
      fluoro-p-hydroxycinnamate and five analogues. Pro-1 was discovered to form a
      bifurcated hydrogen bond between its protonated nitrogen and carboxylate oxygens
      of E-ligands and Tyr-36. No hydrogen bonds were found between Pro-1 and Z
      ligands. This distinct binding characteristic of E- and Z-ligands with Pro-1 may
      be the main factor for the large difference in their binding affinities, which is
      consistent with the previous report that Pro-1 is essential for the catalytic
      activity of MIF. MM-PBSA analysis revealed that energy components including van
      der Waals, electrostatic, and hydrophobic interactions are in favor of binding,
      among which electrostatic interactions are predominant to the binding affinity
      difference.

PMID- 16279780
TI  - Synthesis of N-{4-[(2,4-diamino-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6
      yl)thio]benzoyl}-L-glutamic acid and N-{4-[(2-amino-4-oxo-5-methyl-4,7-dihydro-3H
      pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid as dual inhibitors of
      dihydrofolate reductase and thymidylate synthase and as potential antitumor
      agents.
AB  - Two novel classical antifolates N-{4-[(2,4-diamino-5-methyl-4,7-dihydro-3H
      pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid 3 and N-{4-[(2-amino-4
      oxo-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic
      acid 4 were designed, synthesized, and evaluated as antitumor agents. Compounds 3
      and 4 were obtained from 2,4-diamino-5-methylpyrrolo[2,3-d]pyrimidine 7 and 2
      amino-4-oxo-5-methylpyrrolo[2,3-d]pyrimidine 12, respectively, in a concise three
      step sequence. Compound 3 is the first example, to our knowledge, of a 2,4
      diamino classical antifolate that has potent inhibitory activity against both
      human dihydrofolate reductase (DHFR) and human thymidylate synthase (TS).
      Compound 4 was a dual DHFR-TS inhibitor against the bifunctional enzyme derived
      from Toxoplasma gondii (tg). Further evaluation of the mechanism of action of 3
      implicated DHFR as its primary intracellular target. Both 3 and 4 were
      folylpolyglutamate synthetase (FPGS) substrates. Compound 3 also inhibited the
      growth of several human tumor cell lines in culture with GI50 < 10(-8) M. This
      study shows that the pyrrolo[2,3-d]pyrimidine scaffold is conducive to dual DHFR
      TS and tumor inhibitory activity, and the potency is determined by the 4-position
      substituent.

PMID- 16279781
TI  - Design, synthesis, and biological evaluation of dual binding site
      acetylcholinesterase inhibitors: new disease-modifying agents for Alzheimer's
      disease.
AB  - New dual binding site acetylcholinesterase (AChE) inhibitors have been designed
      and synthesized as new potent drugs that may simultaneously alleviate cognitive
      deficits and behave as disease-modifying agents by inhibiting the beta-amyloid (A
      beta) peptide aggregation through binding to both catalytic and peripheral sites
      of the enzyme. Particularly, compounds 5 and 6 emerged as the most potent
      heterodimers reported so far, displaying IC50 values for AChE inhibition of 20
      and 60 pM, respectively. More importantly, these dual AChE inhibitors inhibit the
      AChE-induced A beta peptide aggregation with IC50 values 1 order of magnitude
      lower than that of propidium, thus being the most potent derivatives with this
      activity reported up to date. We therefore conclude that these compounds are very
      promising disease-modifying agents for the treatment of Alzheimer's disease (AD).

PMID- 16279782
TI  - Cellular apoptosis and cytotoxicity of phenolic compounds: a quantitative
      structure-activity relationship study.
AB  - In this comprehensive study on the caspase-mediated apoptosis-inducing effect of
      51 substituted phenols in a murine leukemia cell line (L1210), we determined the
      concentrations needed to induce caspase activity by 50% (I50) and utilized these
      data to develop the following quantitative structure-activity relationship (QSAR)
      model: log 1/I50 = 1.06 B5(2) + 0.33 B5(3) - 0.18pi(2,4) - 0.92. B5(3) and B5(2)
      represent steric terms, while pi(2,4) represents the hydrophobic character of the
      substituents on the ring. The strong dependence of caspase-mediated apoptosis on
      mostly steric parameters suggests that the process is a receptor-mediated
      interaction with caspases or mitochondrial proteins being the likely targets.
      Conversely, cytotoxicity studies of 65 electron-releasing phenols in the L1210
      cell line led to the development of the following equation: log 1/ID50 = 
      1.39sigma+ - 0.28 B5(2,6) + 0.16 log P - 0.58I(2) - 1.04I(1) + 3.90. The low
      coefficient with log P may pertain to cellular transport that may be enhanced by
      a modest increase in overall hydrophobicity, while the presence of sigma+ is
      consistent with the suggestion that radical stabilization is of prime importance
      in the case of electron-releasing substituents. On the other hand, the QSAR for
      the interactions of 27 electron-attracting phenols in L1210 cells, log 1/ID50 =
      0.56 log P - 0.30 B5(2) + 2.79, suggests that hydrophobicity, as represented by
      log P is of critical importance. Similar cytotoxicity patterns are observed in
      other mammalian cell lines such as HL-60, MCF-7, CCRF-CEM, and CEM/VLB. The
      significant differences between the cytotoxicity and apoptosis QSAR for electron
      releasing phenols suggest that cytotoxicity involves minimal apoptosis in most of
      these substituted monophenols.

PMID- 16279783
TI  - Structural, mutagenic, and kinetic analysis of the binding of substrates and
      inhibitors of human phenylethanolamine N-methyltransferase.
AB  - The X-ray structure of human phenylethanolamine N-methyltransferase (hPNMT)
      complexed with its product, S-adenosyl-L-homocysteine (4), and the most potent
      inhibitor reported to date, SK&F 64139 (7), was used to identify the residues
      involved in inhibitor binding. Four of these residues, Val53, Lys57, Glu219 and
      Asp267, were replaced, in turn, with alanine. All variants had increased Km
      values for phenylethanolamine (10), but only D267A showed a noteworthy (20-fold)
      decrease in its kcat value. Both WT hPNMT and D267A had similar kcat values for a
      rigid analogue, anti-9-amino-6-(trifluoromethyl)benzonorbornene (12), suggesting
      that Asp267 plays an important role in positioning the substrate but does not
      participate directly in catalysis. The Ki values for the binding of inhibitors
      such as 7 to the E219A and D267A variants increased by 2-3 orders of magnitude.
      Further, the inhibitors were shown to bind up to 50-fold more tightly in the
      presence of S-adenosyl-L-methionine (3), suggesting that the binding of the
      latter brings about a conformational change in the enzyme.

PMID- 16279784
TI  - Radioiodinated flavones for in vivo imaging of beta-amyloid plaques in the brain.
AB  - In vivo imaging of beta-amyloid (A beta) peptide aggregates in the brain may lead
      to early detection of Alzheimer's disease (AD) and monitoring of the progression
      and effectiveness of AD treatment. The purpose of this study was to develop novel
      amyloid imaging agents based on flavone as a core structure. Radioiodinated
      flavone derivatives were designed and synthesized. The binding affinities of
      flavone derivatives for A beta aggregates varied from 13 to 77 nM. When in vitro
      plaque labeling was carried out using post-mortem AD brain sections, all flavones
      intensely stained not only amyloid plaques but also cerebrovascular amyloids. In
      biodistribution studies using normal mice, they displayed high brain uptakes
      ranging from 3.2 to 4.1% ID/g at 2 min postinjection. The radioactivity washed
      out from the brain rapidly (0.5-1.9% ID/g at 30 min), which is highly desirable
      for amyloid imaging agents. The results in the study suggest that these classes
      of radioiodinated flavones may be useful candidates as potential imaging agents
      for amyloid plaques.

PMID- 16279785
TI  - Synthesis and evaluation of estrogen receptor ligands with bridged oxabicyclic
      cores containing a diarylethylene motif: estrogen antagonists of unusual
      structure.
AB  - A new series of ligands for the estrogen receptor (ER) based on a three
      dimensional structural motif consisting of a bridged oxabicyclic core (7
      oxabicyclo[2.2.1]heptene or heptadiene) were synthesized and examined for their
      receptor binding activity and as regulators of transcription through the two ER
      subtypes, ER alpha and ER beta. The prototypical ligands also contain a 1,2
      diarylethylene motif, common to many nonsteroidal estrogens, as an embellishment
      on the oxabicyclic core. Thus, these ligands bear peripheral groups typically
      found in ER ligands, built here upon an overall three-dimensional core topology
      that is unusual for these targets. Most of these compounds were conveniently
      synthesized by a Diels-Alder reaction of various 3,4-diarylfurans with a variety
      of dienophiles, neat and under mild conditions in the absence of catalysts. Some
      of the synthesized compounds display good binding affinity for the ER, and in
      transcription assays, the highest affinity compounds are antagonists on both ERs.
      Molecular modeling studies suggest a structural basis for the antagonist activity
      of these compounds. These compounds, based on the bicyclo[2.2.1]core system,
      expand the structural diversity of ligands that can be antagonists for the
      estrogen receptors.

PMID- 16279786
TI  - Piperazinobenzopyranones and phenalkylaminobenzopyranones: potent inhibitors of
      breast cancer resistance protein (ABCG2).
AB  - In continuing research that led us to identify chromanone derivatives (J. Med.
      Chem. 2003, 46, 2125) as P-glycoprotein inhibitors, we obtained analogues able to
      modulate multidrug resistance (MDR) mediated by the breast cancer resistance
      protein (BCRP). The linkage of 5-hydroxybenzopyran-4-one to piperazines or
      phenalkylamines affords highly potent inhibitors of BCRP. By using sensitive
      (HCT116) and resistant colon cancer cells expressing BCRP, we evaluated the
      effect of 14 benzopyranone (chromone) derivatives on the accumulation and the
      cytotoxic effect of the anticancer drug, mitoxantrone. At 10 microM, three
      compounds increased both intracellular accumulation and cytotoxicity of
      mitoxantrone in HCT116/R cells with a comparable rate as fumitremorgin C and
      Gleevec used as reference inhibitors. The most potent molecules 5b and 5c are
      still active at 1 microM, whereas FTC shows weak inhibition. These molecules do
      not induce cell death as shown by the cell cycle distribution study, which makes
      them potential candidates for in vivo studies.

PMID- 16279787
TI  - Enantioselective nonsteroidal aromatase inhibitors identified through a
      multidisciplinary medicinal chemistry approach.
AB  - To identify enantioselective nonsteroidal aromatase inhibitors, a
      multidisciplinary medicinal chemistry approach was pursued. First, our earlier
      CoMFA model [Bioorg. Med. Chem. 1998,6, 377-388] was extended taking purposely
      into account previously discovered enantioselective aromatase inhibitors. The 3D
      QSAR model was then exploited to design chiral ligands, whose configurational
      assignment was obtained, after HPLC separation, by means of a combination of
      circular dichroism measurements and time dependent density functional
      calculations. Finally, the new enantiomeric inhibitors were separately tested to
      ascertain both their potency against the cytochrome P450 aromatase (CYP19; EC
      1.14.14.1), and their selectivity relative to another enzyme of the P450 family.
      A satisfactory agreement between experimental and predicted data allowed us to
      assert that a properly built "enantioselective CoMFA model" might constitute a
      useful tool for addressing enantioselective ligands design.

PMID- 16279788
TI  - Urotensin-II receptor ligands. From agonist to antagonist activity.
AB  - Urotensin II (U-II) is a disulfide bridged peptide hormone recently identified as
      the ligand of a G-protein-coupled receptor. Human U-II (H-Glu-Thr-Pro-Asp
      cyclo[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) has been described as the most potent
      vasoconstrictor compound identified to date. We have recently identified both a
      superagonist of hU-II termed P5U and the compound termed urantide, which is the
      most potent UT receptor peptide antagonist described to date. Our previous
      conformational studies showed that hU-II and its analogues with agonist activity
      adopt a well-defined type II' beta-hairpin structure in anisotropic SDS membrane
      like environment. This structural arrangement allows tight contact among the
      Trp7, Lys8, and Tyr9 side chains, which is fundamental to obtain full agonist
      activity. Here, we report an extensive SAR study on new analogues with
      agonist/antagonist activity on UT receptor. We investigated their biological
      activity and performed a conformational analysis by spectroscopic and
      computational methods. Our goal is to obtain a structure-based model able to
      explain the agonist/antagonist functional switching of these ligands.

PMID- 16279789
TI  - Light-induced anticancer activity of [RuCl2(DMSO)4] complexes.
AB  - The cytotoxicity and photocytotoxicity of trans-[RuCl2(DMSO)4] and cis
      [RuCl2(DMSO)4] complexes was tested in two melanoma cell lines, human (SK-MEL
      188) and mouse (S91). The trans isomer was found to be more effective for cell
      growth inhibition than its cis analogue both in the presence and in the absence
      of illumination. However, the antiproliferative activity of both isomers was
      significantly enhanced after irradiation with UVA light in comparison with their
      activity observed in the dark. The influence of light on the reaction of both
      ruthenium(II) isomers with the single-stranded hexanucleotide d(T2GGT2), chosen
      as a model system for DNA, was also studied using chromatography and mass
      spectrometry techniques. The photochemical reaction of the ruthenium(II)
      complexes with the oligonucleotide d(T2GGT2) resulted in the formation of Ru(G
      N7)2 adducts, which was not observed in the same time scale in thermal reactions.
      The initial short irradiation of the inert cis isomer was found to facilitate the
      covalent adduct formation with d(T2GGT2) in the secondary thermal reactions and
      with a rate comparable to that found for the trans isomer, which is ca. 5-10
      times more reactive in the dark.

PMID- 16279790
TI  - Synthesis and biological activity of anticancer ether lipids that are
      specifically released by phospholipase A2 in tumor tissue.
AB  - The clinical use of anticancer lipids is severely limited by their ability to
      cause lysis of red blood cells prohibiting intravenous injection. Novel delivery
      systems are therefore required in order to develop anticancer ether lipids (AELs)
      into clinically useful anticancer drugs. In a recent article (J. Med. Chem. 2004,
      47, 1694) we showed that it is possible to construct liposome systems composed of
      masked AELs that are activated by secretory phospholipase A2 in cancerous tissue.
      We present here the synthesis of six AELs and evaluate the biological activity of
      these bioactive lipids. The synthesized AEL 1-6 were tested against three
      different cancer cell lines. It was found that the stereochemistry of the
      glycerol headgroup in AEL-2 and 3 has a dramatic effect on the cytotoxicity of
      the lipids. AEL 1-4 were furthermore evaluated for their ability to prevent
      phosphorylation of the apoptosis regulating kinase Akt, and a correlation was
      found between their cytotoxic activity and their ability to inhibit Akt
      phosphorylation.

PMID- 16279791
TI  - Synthesis and evaluation of quindoline derivatives as G-quadruplex inducing and
      stabilizing ligands and potential inhibitors of telomerase.
AB  - A new series of quindoline derivatives (4a-j) were designed and synthesized to
      develop novel and potent telomerase inhibitors. The interaction of the G
      quadruplex of human telomere DNA with these newly designed molecules was examined
      via circular dichroism spectroscopy and electrophoretic mobility shift assay
      (EMSA). The selectivity between the quindoline derivative (4a) and G-quadruplex
      or duplex DNA was investigated by competition dialysis. These new compounds as
      inhibitors of telomerase were also investigated through the utilization of
      modified telomerase repeat amplification protocol (TRAP) assay. The results
      revealed that the introduction of electron-donating groups such as substituted
      amino groups at the C-11 position of quindoline significantly improved the
      inhibitory effect on telomerase activity ((Tel)IC50 > 138 microM for quindoline,
      0.44-12.3 microM for quindoline derivatives 4a-j). The quindoline derivatives not
      only stabilized the G-quadruplex structure but also induced the G-rich telomeric
      repeated DNA sequence to fold into quadruplex.

PMID- 16279792
TI  - Application of validated QSAR models of D1 dopaminergic antagonists for database
      mining.
AB  - Rigorously validated quantitative structure-activity relationship (QSAR) models
      have been developed for 48 antagonists of the dopamine D1 receptor and applied to
      mining chemical datasets to discover novel potential antagonists. Several QSAR
      methods have been employed, including comparative molecular field analysis
      (CoMFA), simulated annealing-partial least squares (SA-PLS), k-nearest neighbor
      (kNN), and support vector machines (SVM). With the exception of CoMFA, these
      approaches employed 2D topological descriptors generated with the MolConnZ
      software package (EduSoft, LLC. MolconnZ, version 4.05;
      http://www.eslc.vabiotech.com/ [4.05], 2003). The original dataset was split into
      training and test sets to allow for external validation of each training set
      model. The resulting models were characterized by cross-validated R2 (q2) for the
      training set and predictive R2 values for the test set of (q2/R2) 0.51/0.47 for
      CoMFA, 0.7/0.76 for kNN, R2 for the training and test sets of 0.74/0.71 for SVM,
      and training set fitness and test set R2 values of 0.68/0.63 for SA-PLS.
      Validated QSAR models with R2 > 0.7, (i.e., kNN and SVM) were used to mine three
      publicly available chemical databases: the National Cancer Institute (NCI)
      database of ca. 250,000 compounds, the Maybridge Database of ca. 56,000
      compounds, and the ChemDiv Database of ca. 450,000 compounds. These searches
      resulted in only 54 consensus hits (i.e., predicted active by all models); five
      of them were previously characterized as dopamine D1 ligands, but were not
      present in the original dataset. A small fraction of the purported D1 ligands did
      not contain a catechol ring found in all known dopamine full agonist ligands,
      suggesting that they may be novel structural antagonist leads. This study
      illustrates that the combined application of predictive QSAR modeling and
      database mining may provide an important avenue for rational computer-aided drug
      discovery.

PMID- 16279793
TI  - Inhibitors of tripeptidyl peptidase II. 3. Derivation of butabindide by
      successive structure optimizations leading to a potential general approach to
      designing exopeptidase inhibitors.
AB  - The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase that
      has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC
      3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to
      give Asp-Tyr(SO3H)-Met-OH + Gly-Trp-Met-Asp-Phe-NH2. Starting from Val-Pro-NHBu,
      a dipeptide of submicromolar affinity that had previously been generated to serve
      as a lead, successive optimization at P3, P1, and then P2 gave Abu-Pro-NHBu (18,
      Ki = 80 nM). Further transformation (by making a benzologue) gave the indoline
      analogue, butabindide (33) as a reversible inhibitor having nanomolar affinity
      (Ki = 7 nM). Retrospective analysis suggested the possibility of a general
      approach to designing exopeptidase inhibitors starting from the structure of the
      first hydrolysis product. Application of this approach to CCK-8 led to Abu-Phe
      NHBu (37), but this only had Ki = 9.4 microM. Molecular modeling, to determine
      the minimum energy conformations and explain the 1000-fold better affinity of
      butabindide, indicated that 37 cannot access the likely active conformation of
      butabindide.

PMID- 16279794
TI  - Design, synthesis, and binding studies of new potent ligands of cannabinoid
      receptors.
AB  - Despite their different chemical structures, delta9-tetrahydrocannabinol (THC)
      and anandamide (AEA) have common pharmacological properties. This study was aimed
      at finding new cannabinoid receptor ligands that overcome the instability of AEA
      and its analogues. To this end we planned the synthesis of a series of compounds
      which retained both a rigid structure, like that of plant cannabinoids, and a
      flexible portion similar to that of anandamide. Binding studies on CB1 and CB2
      receptors, anandamide membrane transporter (AMT), and fatty acid amide hydrolase
      (FAAH) showed that some of the newly developed compounds have high affinity and
      specificity for cannabinoid CB1 and CB2 receptors. Compound 25 is a potent CB1
      and CB2 ligand, with affinity constants significantly lower than AEA and similar
      to WIN 55-212, compound 52 is a potent CB2 ligand, although not very selective
      over CB1 receptors, and compound 43 is CB2 ligand, with at least a 26-fold
      selectivity over CB1 receptors. Compound 25 behaved as a inverse agonist at CB1
      receptors as assessed in the cyclic AMP functional assay.

PMID- 16279795
TI  - Tricyclic pyrazoles. 3. Synthesis, biological evaluation, and molecular modeling
      of analogues of the cannabinoid antagonist 8-chloro-1-(2',4'-dichlorophenyl)-N
      piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3
      carboxamide.
AB  - A series of analogues of 8-chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl
      1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide 4a (NESS
      0327) (Ruiu, S.; Pinna, G. A.; Marchese, G.; Mussinu, J. M.; Saba, P.; Tambaro,
      S.; Casti, P.; Vargiu, R.; Pani, L. Synthesis and Characterization of NESS 0327:
      A Novel Putative Antagonist of CB1 Cannabinoid Receptor. J. Pharmacol. Exp. Ther.
      2003, 306, 363-370) was synthesized and evaluated for their affinity to
      cannabinoid receptors. Depending on the chemical modification of the lead
      structure that was chosen, compounds 4b, 4c, 4i, 4l, and 4m still proved to be
      potent binders of the CB1 receptor. Moreover, several analogues (4c, 4d, 4e, and
      4m) demonstrated superior CB2 receptor binding affinities compared to the parent
      ligand. Compounds 4b, 4c, 4i, and 4l displayed the most promising pharmacological
      profiles, having the highest selectivity for CB1 receptors with Ki(CB2) to
      Ki(CB1) ratios of 11,250, 2000, 3330 and 4625, respectively. Compound 4c
      increased the intestinal propulsion in mice and antagonized the effect induced by
      the CB1 receptor agonist WIN 55,212-2. Finally, molecular modeling studies were
      carried out on a set of tricyclic pyrazoles (2a-4a) and on rimonabant 1
      (SR141716A), indicating that high CB1 receptors affinities were consistent for
      the tricyclic derivatives, both with a nonplanar geometry of the tricyclic cores
      and with a precise orientation of the substituent (chlorine) on this ring system.

PMID- 16279796
TI  - Novel benzopyridothiadiazepines as potential active antitumor agents.
AB  - The synthesis of novel thiadiazepine derivatives, that could be considered as
      constraint analogues of E-7010, are reported. These molecules were evaluated for
      their antiproliferative activity toward the murine L1210 leukemia cell line. Flow
      cytometric studies performed on L1210 cells with the most cytotoxic compounds
      showed an accumulation of the cells in the G2/M phases of the cell cycle with a
      significant percentage of tetraploid cells (8N DNA content). Submicromolar
      cytotoxicities were observed with compounds 2b, 4b, 4e, 4g, and 4i. Two of them,
      compounds 2b and 4b, were found to be potent inhibitors of tubulin polymerization
      with IC50 of respectively 3.8 and 2.4 microM compared to 2.4 microM for
      desoxypodophyllotoxin. A 4-methoxyphenylethyl substitution on the pyridinyl
      nitrogen of the benzopyridothiadiazepine was found to be essential for the
      antiproliferative activity. The in vitro activities of compounds 2b and 4b make
      benzopyridothiadiazepine dioxides a promising new class of tubulin binders which
      warrant further in vivo evaluation.

PMID- 16279797
TI  - Structure-activity relationship of triazafluorenone derivatives as potent and
      selective mGluR1 antagonists.
AB  - SAR (structure-activity relationship) studies of triazafluorenone derivatives as
      potent mGluR1 antagonists are described. The triazafluorenone derivatives are non
      amino acid derivatives and noncompetitive mGluR1 antagonists that bind at a
      putative allosteric recognition site located within the seven-transmembrane
      domain of the receptor. These triazafluorenone derivatives are potent, selective,
      and systemically active mGluR1 antagonists. Compound 1n, for example, was a very
      potent mGluR1 antagonist (IC50 = 3 nM) and demonstrated full efficacy in various
      in vivo animal pain models.

PMID- 16279798
TI  - Delta9-tetrahydrocannabinol immunochemical studies: haptens, monoclonal
      antibodies, and a convenient synthesis of radiolabeled delta9
      tetrahydrocannabinol.
AB  - Immunopharmacotherapy as an approach to combat drugs of abuse has become an
      active area of investigation. Marijuana is the most commonly used illicit drug in
      the U.S. The main active chemical in marijuana is delta9-tetrahydrocannabinol
      (delta9-THC); hence, monoclonal antibodies with high affinity and specificity for
      delta9-tetrahydrocannabinol could be valuable immunopharmacotherapeutic
      intervention and diagnostic tools. We have synthesized immunoconjugates that
      induce an effective immune response to delta9-THC and describe a convenient
      synthesis of radiolabeled delta9-THC. We demonstrate the value and use of this
      probe to select anti-delta9-THC antibodies that bind delta9-THC with good
      affinity. The synthetic route to radiolabeled delta9-THC has enabled the correct
      assessment of the affinity of these antibodies to their ligand and may facilitate
      future binding studies between delta9-THC and its analogues and the cannabinoid
      receptors.

PMID- 16279799
TI  - Irreversible inactivation of trypanothione reductase by unsaturated Mannich
      bases: a divinyl ketone as key intermediate.
AB  - Trypanothione reductase is a flavoenzyme unique to trypanosomatid parasites. Here
      we show that unsaturated Mannich bases irreversibly inactivate trypanothione
      reductase from Trypanosoma cruzi, the causative agent of Chagas' disease. The
      inhibitory potency of the compounds strongly increased upon storage of the DMSO
      stock solutions. HPLC, NMR, and mass spectrometry data of potential intermediates
      revealed a divinyl ketone as the active compound inactivating the enzyme. ESI-
      and MALDI-TOF mass spectrometry of trypanothione reductase modified by the
      Mannich base or the divinyl ketone showed specific alkylation of the active site
      Cys52 by a 5-(2'chlorophenyl)-3-oxo-4-pentenyl substituent. The reaction
      mechanism and the site of alkylation differ from those in Plasmodium falciparum
      thioredoxin reductase where the C-terminal redox active dithiol is modified.
      After deamination, unsaturated Mannich bases are highly reactive in
      polycondensation with trypanothione. Interaction of these compounds with both
      trypanothione and trypanothione reductase could account for their potent
      trypanocidal effect against Trypanosoma brucei.

PMID- 16279800
TI  - Damicoside from Axinella damicornis: the influence of a glycosylated galactose 4
      OH group on the immunostimulatory activity of alpha-galactoglycosphingolipids.
AB  - Alpha-galactoglycosphingolipids (alpha-GalGSLs) are unique immunostimulatory
      glycosphingolipids from marine sponges. Analysis of the glycosphingolipid
      composition of the marine sponge Axinella damicornis revealed the presence of a
      new alpha-GalGSL, damicoside (3a), which is the first alpha-GalGSL with a
      glycosylated galactose 4-OH group. Structure elucidation of damicoside was
      performed using spectroscopic and chemical methods. When tested in a spleen cell
      proliferation assay, 3a exhibited a stimulatory activity comparable to that of
      agelasphin (2), showing that a free galactose 4-OH group is not essential for the
      immunostimulatory activity of alpha-GalGSLs and providing a further step toward
      the complete understanding of their structure-activity relationship.

PMID- 16279801
TI  - Analysis of peptide-protein binding using amino acid descriptors: prediction and
      experimental verification for human histocompatibility complex HLA-A0201.
AB  - Amino acid descriptors are often used in quantitative structure-activity
      relationship (QSAR) analysis of proteins and peptides. In the present study,
      descriptors were used to characterize peptides binding to the human MHC allele
      HLA-A0201. Two sets of amino acid descriptors were chosen: 93 descriptors taken
      from the amino acid descriptor database AAindex and the z descriptors defined by
      Wold and Sandberg. Variable selection techniques (SIMCA, genetic algorithm, and
      GOLPE) were applied to remove redundant descriptors. Our results indicate that
      QSAR models generated using five z descriptors had the highest predictivity and
      explained variance (q2 between 0.6 and 0.7 and r2 between 0.6 and 0.9). Further
      to the QSAR analysis, 15 peptides were synthesized and tested using a T2
      stabilization assay. All peptides bound to HLA-A0201 well, and four peptides were
      identified as high-affinity binders.

PMID- 16279802
TI  - Exploratory chemistry toward the identification of a new class of multidrug
      resistance reverters inspired by pervilleine and verapamil models.
AB  - On the basis of the present knowledge of the substrate recognition site of ABC
      transporter proteins and inspired by the structures of verapamil and pervilleine
      A, a new class of Pgp-mediated multidrug resistance (MDR) reverters has been
      designed and synthesized. The new compounds are flexible molecules carrying one
      or two basic nitrogen atoms flanked, at properly modulated distance, by two
      aromatic moieties. Most of the molecules studied possess MDR inhibitory activity
      on anthracycline-resistant erythroleukemia K 562 cells, showing a potency that is
      higher than that of the reference compound verapamil and, in a few cases (7, 12,
      13,17, 20, 22, 28), is in the high nanomolar range. These compounds may be useful
      leads to develop new MDR reverting agents. In fact, the chemical structure of the
      class is fairly simple and can be implemented in a variety of ways that will
      allow the synthesis of new compounds that might be useful leads for the
      development of drugs to control Pgp-dependent MDR.

PMID- 16279803
TI  - Synthesis and monoamine transporter binding properties of 2,3-diaryltropanes.
AB  - Synthetic procedures were developed for the synthesis of 2beta,3beta- and
      2alpha,3alpha-diaryltropanes. These compounds are analogues of the 3-aryltropane
      2beta-carboxylic acid methyl ester class of monoamine uptake inhibitors, where
      the 2beta-carbomethoxy group has been replaced by an aryl group. The compounds
      were evaluated for inhibition of radioligand binding at the dopamine,
      norepinephrine, and serotonin transporters (DAT, NET, and 5-HTT, respectively).
      The results showed that the replacement of the 2beta-carbomethoxy group in the 3
      aryltropane class with a 2beta-aryl group led to compounds possessing very
      similar monoamine transporter binding properties. However, the 2beta,3beta
      diaryltropanes tended to be more potent at the DAT and more selective for the DAT
      relative to the NET and 5-HTT. One of the most interesting compounds was 3beta-(4
      methylphenyl)-2beta-(4-methylphenyl)tropane (3d), which showed an IC50 of 1.23 nM
      at the DAT with 289- and 185-fold selectivity for the DAT relative to the NET and
      5-HTT. The 2alpha,3alpha-diaryltropanes were much less potent at all three
      transporters than 2beta,3beta-diaryltropanes.

PMID- 16279804
TI  - Anilinodialkoxyquinazolines: screening epidermal growth factor receptor tyrosine
      kinase inhibitors for potential tumor imaging probes.
AB  - The epidermal growth factor receptor (EGFR), a long-standing drug development
      target, is also a desirable target for imaging. Sixteen dialkoxyquinazoline
      analogues, suitable for labeling with positron-emitting isotopes, have been
      synthesized and evaluated in a battery of in vitro assays to ascertain their
      chemical and biological properties. These characteristics provided the basis for
      the adoption of a selection schema to identify lead molecules for labeling and in
      vivo evaluation. A new EGFR tyrosine kinase radiometric binding assay revealed
      that all of the compounds possessed suitable affinity (IC50 = 0.4-51 nM) for the
      EGFR tyrosine kinase. All of the analogues inhibited ligand-induced EGFR tyrosine
      phosphorylation (IC50 = 0.8-20 nM). The HPLC-estimated octanol/water partition
      coefficients ranged from 2 to 5.5. Four compounds, 4-(2'-fluoroanilino)- and 4
      (3'-fluoroanilino)-6,7-diethoxyquinazoline as well as 4-(3'-chloroanilino)- and 4
      (3'-bromoanilino)-6,7-dimethoxyquinazoline, possess the best combination of
      characteristics that warrant radioisotope labeling and further evaluation in
      tumor-bearing mice.

PMID- 16279805
TI  - Discovery of novel and potent small-molecule inhibitors of NO and cytokine
      production as antisepsis agents: synthesis and biological activity of alkyl 6-(N
      substituted sulfamoyl)cyclohex-1-ene-1-carboxylate.
AB  - To develop a new therapeutic agent for sepsis, screening of the Takeda chemical
      library was carried out using mouse macrophages stimulated with
      lipopolysaccharide (LPS) to identify a new class of small-molecule inhibitors of
      inflammatory mediator production. The lead compound 5a was discovered, from which
      a series of novel cyclohexene derivatives I bearing a sulfamoyl and ester group
      were designed, synthesized and tested for their inhibitory activity against
      nitric oxide (NO) production. Derivatives I were synthesized by the coupling of
      sulfonyl chlorides and anilines with concomitant double bond migration in the
      presence of triethylamine, and phenyl ring substitution and modification of the
      ester and cyclohexene moieties were carried out. Among the compounds synthesized,
      ethyl (6R)-6-[N-(2-chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate
      [(R)-(+)-5n, TAK-242] was found to exhibit the most potent suppressive activity
      for the production of not only NO but also inflammatory cytokines, such as tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) induced by LPS
      stimulated mouse macrophages with IC50 values of 1.8, 1.9 and 1.3 nM,
      respectively. It shows marked beneficial effects in vivo also. Intravenous
      administration of (R)-(+)-5n at doses of 0.1 mg/kg or more suppressed the
      production of NO and various cytokines [TNF-alpha, IL-6 and IL-1beta] in the
      mouse endotoxin shock model. Furthermore, it protected mice from death dose
      dependently and all mice survived at a dose of 3 mg/kg. The minimum effective
      dose to protect mice from lethality in this model was 0.3 mg/kg, which was
      consistent with those for inhibitory effects on the production of NO and
      cytokines. Compound (R)-(+)-5n is currently undergoing clinical trials for the
      treatment of sepsis.

PMID- 16279806
TI  - Identification of borinic esters as inhibitors of bacterial cell growth and
      bacterial methyltransferases, CcrM and MenH.
AB  - As bacteria continue to develop resistance toward current antibiotics, we find
      ourselves in a continual battle to identify new antibacterial agents and targets.
      We report herein a class of boron-containing compounds termed borinic esters that
      have broad spectrum antibacterial activity with minimum inhibitory concentrations
      (MIC) in the low microgram/mL range. These compounds were identified by screening
      for inhibitors against Caulobacter crescentus CcrM, an essential DNA
      methyltransferase from gram negative alpha-proteobacteria. In addition, we
      demonstrate that borinic esters inhibit menaquinone methyltransferase in gram
      positive bacteria using a new biochemical assay for MenH from Bacillus subtilis.
      Our data demonstrate the potential for further development of borinic esters as
      antibacterial agents as well as leads to explore more specific inhibitors against
      two essential bacterial enzymes.

PMID- 16279807
TI  - Statistical tools for virtual screening.
AB  - In large-scale virtual screening (VS) campaigns, data are often computed for
      millions of compounds to identify leads, but there remains the task of
      prioritizing VS "hits" for experimental assays and the dilemma of assessing
      true/false positives. We present two statistical methods for mining large
      databases: (1) a general scoring metric based on the VS signal-to-noise level
      within a compound neighborhood; (2) a neighborhood-based sampling strategy for
      reducing database size, in lieu of property-based filters.

PMID- 16279808
TI  - Synthesis of two 3,5-disubstituted sulfonamide catechol ligands and evaluation of
      their iron(III) complexes for use as MRI contrast agents.
AB  - Two 3,5-disubstituted sulfonamide catechol ligands were synthesized. Tris(ligand)
      iron(III) complexes were prepared and investigated as MRI contrast agents.
      Longitudinal relaxivity (r1) values were determined for the complexes. The r1
      values in water were substantially higher than those of typical six-coordinate
      iron(III) complexes. The r1 values in plasma under the same conditions increased.
      The iron(III) complexes were administered to rats, and the kidney and liver
      signal intensities were measured by T1-weighted MR imaging experiments.

PMID- 16279809
TI  - 1-Benzhydryl-3-phenylurea and 1-benzhydryl-3-phenylthiourea derivatives: new
      templates among the CB1 cannabinoid receptor inverse agonists.
AB  - New 1-benzhydryl-3-phenylurea derivatives and their 1-benzhydryl-3-phenylthiourea
      isosteres were synthesized and evaluated for their human CB1 and CB2 cannabinoid
      receptor affinity. These compounds proved to be selective CB1 cannabinoid
      receptor ligands, acting as inverse agonists in a [35S]-GTPgammaS assay. The
      affinity of 3,5,5'-triphenylimidazolidine-2,4-dione and 3,5,5'-triphenyl-2
      thioxoimidazolidin-4-one derivatives, possessing the 1-benzhydryl-3-phenylurea
      and 1-benzhydryl-3-phenylthiourea moiety, respectively, was also evaluated. In
      conclusion, the 1-benzhydryl-3-phenylurea scaffold seems to be a new interesting
      template of CB1 cannabinoid receptor inverse agonists.

PMID- 16279811
TI  - Random chemistry as a new tool for the generation of small compound libraries:
      development of a new acetylcholinesterase inhibitor.
AB  - Random chemistry, the serendipitous generation of small compound libraries by
      gamma-irradiation of source compounds, presents a methodology providing
      reassembled and rearranged structures. The gamma-irradiation was applied to
      generate new acetylcholinesterase (AChE) inhibitors. The bioassay-guided
      fractionation as a deconvolution strategy was employed to analyze gained product
      mixture. The structure of the new highly potent AChE inhibitor, 9-amino-5,6,7,8
      tetrahydroacridin-4yl)methanol (1), was elucidated by NMR spectroscopy and ESI
      (tandem) mass spectrometry.

PMID- 16279813
TI  - Reviewing the literature traditional, systematic, evidence-based.

PMID- 16279815
TI  - Re: Hsieh TJ, et al. Assessment of orthodontic treatment outcomes: early
      treatment vs late treatment. Angle Orthod. 2005;75:162-170.

PMID- 16279810
TI  - Synthesis and pharmacological characterization of exo-2-(2'-chloro-5-pyridinyl)-7
      (endo and exo)-aminobicyclo[2.2.1]heptanes as novel epibatidine analogues.
AB  - Procedures were developed for the synthesis of exo-(2'-chloro-5-pyridinyl)-7
      (endo and exo)-amino[2.2.1]heptanes (3a and 3b). The compounds were evaluated for
      binding to the alpha4beta2 and alpha7 nicotinic acetylcholine receptors (nAChRs),
      for pharmacological activity in the mouse tail-flick and hot-plate assays, and
      for hypothermia and locomotor activity. Compounds 3a and 3b possessed alpha4beta2
      nAChR binding properties similar to those of (-)-nicotine and were nAChR agonists
      in all four mouse assays.

PMID- 16279816
TI  - Re: Response from Dr Hsieh.

PMID- 16279817
TI  - Extraoral vs intraoral appliance for distal movement of maxillary first molars: a
      randomized controlled trial.
AB  - Using randomized controlled trial methodology, the aim of this study was to
      evaluate and compare the treatment effects of an extraoral appliance (EOA) and an
      intraoral appliance (IOA) for distal movement of maxillary first molars. A total
      of 40 patients (mean 11.5 years, SD 1.29) at the Orthodontic Clinic, National
      Health Service, Skane County Council, Malmo, Sweden, were randomized to receive
      treatment with either extraoral traction (cervical headgear) or an IOA using
      superelastic coils for distal movement of maxillary first molars. The inclusion
      criteria were a nonextraction treatment plan, a Class II molar relationship and
      maxillary first molars in occlusion with no erupted maxillary second molars. The
      outcome measures to be assessed in the trial were treatment time, cephalometric
      analysis of distal molar movement, anterior movement of maxillary central
      incisors, ie, anchorage loss and sagittal and vertical skeletal positional
      changes of the maxilla and mandible. In the IOA group, the molars were distalized
      during an average time of 5.2 months, whereas in the EOA group the corresponding
      time was 6.4 months (P < .01). The mean amount of distal molar movement was
      significantly higher in the IOA than in the EOA group, three mm vs 1.7 mm (P <
      .001). Moderate anchorage loss was produced with the IOA implying increased
      overjet (0.9 mm) whereas the EOA created decreased overjet (0.9 mm). It can be
      concluded that the IOA was more effective than the EOA to create distal movement
      of the maxillary first molars.

PMID- 16279818
TI  - Early orthodontic treatment of skeletal open-bite malocclusion: a systematic
      review.
AB  - The aim of this study was a systematic review of the literature to assess the
      scientific evidence on the actual outcome of early treatments of open-bite
      malocclusions. A literature survey was done by applying the Medline database
      (Entrez PubMed). The survey covered the period from January 1966 to July 2004 and
      used the MeSH, Medical Subject Headings. The following study types that reported
      data on the treatment effects included: randomized clinical trials (RCT),
      prospective and retrospective studies with concurrent untreated as well as normal
      controls, and clinical trials comparing at least two treatment strategies without
      any untreated or normal control group involved. The search strategy resulted in
      1049 articles. After selection according to the inclusionary/exclusionary
      criteria, seven articles qualified for the final review analysis. No RCTs of
      early treatment of anterior open bite have been performed. Two controlled
      clinical trials of early anterior open bite have been performed, and these two
      studies indicated the effectiveness of treatment in the mixed dentition with
      headgears or functional appliances (or both). Most of the studies had serious
      problems of lack of power because of small sample size, bias and confounding
      variables, lack of method error analysis, blinding in measurements, and deficient
      or lack of statistical methods. Thus, the quality level of the studies was not
      sufficient enough to draw any evidence-based conclusions.

PMID- 16279819
TI  - Bridging and dimensions of sella turcica in subjects treated by surgical
      orthodontic means or orthodontics only.
AB  - The aim of the study was to compare the incidence of sella turcica bridging and
      sella turcica dimensions in 150 Caucasian subjects who had combined surgical
      orthodontic correction of their malocclusion with a randomly selected group of
      150 Caucasian subjects who were treated contemporaneously by orthodontic means
      only. Pretreatment lateral cephalometric radiographs were scanned and analyzed. A
      sella turcica bridge was identified as a continuous band of bony tissue extending
      from the anterior cranial fossa to the posterior cranial fossa. The dimensions of
      the sella turcica were measured. In the group treated by combined surgical
      orthodontic means, the incidence of bridging was 16.7%, whereas it was 7.3% in
      the orthodontics-only group (P = .012). Significant increases in the mean surface
      area (P = .02) and mean perimeter of the sella turcica (P = .01) were found for
      the combined surgical-orthodontic group compared with the orthodontics-only
      group. The mean interclinoid distance was significantly smaller in the surgical
      orthodontic group (P = .02). These findings appear to indicate the greater
      likelihood of sella turcica bridging and abnormal sella turcica dimensions in
      subjects treated by combined surgical-orthodontic means rather than by
      orthodontics only.

PMID- 16279820
TI  - The relation between the point of force application and flaring of the anterior
      segment.
AB  - The purpose of this study was to determine whether application of an intrusive
      force by an intrusion arch at the distal wings of the lateral incisor brackets
      causes a change in the axial inclination of the anterior segment. Maxillary
      incisor intrusion was performed, and records were taken from 40 adolescent
      patients at the beginning and end of intrusion. Intrusion of the maxillary
      anterior segment caused a statistically significant mean increase in axial
      inclination of the central incisor of 8.74 degrees. The following correlations
      were investigated and found not statistically significant. The correlation
      between the (1) distance from the point of force application to the center of
      resistance at the start of intrusion and the change in axial inclination of the
      incisor, (2) distance from the point of force application to the center of
      resistance at the start of intrusion and the change in distance from the incisal
      edge to the distal side of the first molar, (3) distance from the point of
      intrusive force application to the center of resistance at the start of intrusion
      and at the end of intrusion, (4) distance from the point of intrusive force
      application to the center of resistance at the start of intrusion and the change
      in this distance between start and end of intrusion, and (5) amount of intrusion
      and the change in axial inclination.

PMID- 16279821
TI  - Cephalometric predictors of long-term stability in the early treatment of Class
      III malocclusion.
AB  - The aim of this study was to examine the differences in the early craniofacial
      morphology of Class Ill malocclusions. Lateral cephalograms of 45 subjects with a
      Class III malocclusion and an anterior crossbite in the deciduous or mixed
      dentition were examined before treatment, after treatment, and during the long
      term retention stage. The anterior crossbites of all patients were corrected
      after a series of orthodontic treatments. After a mean follow-up period of 5.7
      years, all the subjects were reevaluated and divided into three groups according
      to the final occlusal status: good, fair, and poor occlusal stability. Twenty
      cephalometric variables on the pretreatment lateral cephalograms were analyzed by
      one-way analysis of variance and discriminant analysis to identify the key
      determinants for discriminating among the three groups. Among the 20 variables,
      11 showed statistical significance. Generally, the subjects with a smaller gonial
      angle and a more hypodivergent skeletal pattern had good prognosis after the
      early treatment of Class III malocclusion. When the AB to mandibular plane angle
      and N-perpendicular to point A were selected in discriminant analysis, the AB to
      mandibular plane angle was the most significant variable. Discriminant analysis
      showed a relatively high degree of correct classifications of the patients with
      early Class III malocclusion. In particular, discriminant analysis showed the
      highest accuracy (93.3%) when predicting a poor prognosis.

PMID- 16279822
TI  - Maxillary molar intrusion with fixed appliances and mini-implant anchorage
      studied in three dimensions.
AB  - The intrusion of an overerupted maxillary molar using traditional orthodontic
      treatment is a real challenge. The aim of this study was to investigate the
      envelope of intrusive movements of a maxillary molar in cases using mini-implants
      as anchorage with partial or full-mouth fixed edgewise appliances. The cusp tips
      of the pretreatment and postintrusion dental casts were recorded by a three
      dimensional (3D) digitizer. The 3D data of the serial dental casts were analyzed
      to distinguish the direction and magnitude of individual tooth movement. The mean
      intrusive movement of the maxillary first molars was three to four mm, with a
      maximum of over eight mm. For the adjacent maxillary second molars and second
      premolars, the amount of intrusion was two mm and 1-2 mm, respectively. This
      study demonstrated that significant true intrusion of maxillary molars could be
      obtained in a well-controlled manner by using fixed appliances with titanium mini
      implants as bony anchorage.

PMID- 16279823
TI  - Effects of a magnetic appliance in functional Class III patients.
AB  - The aim of this study was to determine the effects of a magnetic appliance in
      functional Class III patients. Standardized lateral head cephalograms and hand
      wrist films of 10 subjects (mean age nine years seven months) were taken. These
      records were repeated after a period of one year, and the serial films were
      compared to determine the direction of facial growth as the control group. After
      this observation period, the magnetic appliance was placed in the 10 patients for
      approximately 9.4 months. The significant findings showed a posterior rotation of
      the mandible (x = 2.1 +/- 0.7 degrees), increased overjet (x = 4.8 +/- 0.3 mm),
      decreased overbite (x = -3.7 +/- 0.7 mm), protrusion of the upper incisors (x =
      6.2 +/- 1.2 degrees), retrusion in the lower incisors (x = -0.6 +/- 0.3 degrees),
      reduced SNB angle (x = -1.8 +/- 0.8 degrees), increased ANB angle (x = 1.9 +/-
      0.3 degrees), and an increased mandibular plane angle (x = 2.1 +/- 0.7 degrees).
      The results of this study indicate that the primary effect of magnetic appliance
      was the increase in the posterior rotation of the mandible.

PMID- 16279824
TI  - Muscular forces exerted on the normal deciduous dentition.
AB  - This study evaluated the distributing characteristic of the forces exerting on
      the normal deciduous dentition and the relationship between the muscular forces,
      sex, and oral function. The pressure measurements were made with a computer-aided
      perioral force-measuring system designed by the authors. The forces were measured
      when the subject's head position was in a state of natural head position and oral
      function was at rest or with swallowing. The results indicated that the forces
      from lips, cheeks, and tongue at rest were about 37-208 N/m2, whereas the
      pressure during swallowing was about 1009-1679 N/m2. At rest, the pressure from
      lips and cheeks was higher than that from tongue (P < .05), whereas during
      swallowing, the lingual pressure was statistically larger (P < .001). A
      significant correlation existed between the muscular pressure and sex. When at
      rest, the boy's force from cheeks was higher than that of the girl's (P < .05)
      but during swallowing the boy's labial pressure was statistically higher than
      that of the girl's (P < .01). It was concluded that (1) the deciduous teeth are
      not in a state of absolute balance between external and internal forces, (2) the
      distributing manner and unbalanced mode of the forces are different with the
      different oral functions, (3) the lingual side of the mandibular anterior teeth
      endures great differences during oral functions and it may account for high
      incidence of malocclusion in this segment, and (4) a statistical difference
      between muscular forces and sex exists.

PMID- 16279826
TI  - Prediction of lower permanent canine and premolars width by correlation methods.
AB  - The aim of this study was to determine linear regression equations to estimate
      the widths of unerupted lower permanent canines and premolars using measurements
      obtained from 45 degrees oblique teleradiographs. The sample consisted of 30
      white Caucasian patients orthodontically treated at the Faculty of Dentistry,
      Universidade Federal do Rio de Janeiro. The records for each patient included a
      45 degrees oblique teleradiograph (left side) in the mixed dentition period and a
      dental cast of the permanent dentition. Pearson's test was applied between each
      lower canine, first and second premolars measured on the radiograph, and the sum
      of their actual widths measured on the dental cast. The strongest correlation
      occurred for the first premolars for one side (.82) and both sides (.84). One
      linear regression equation was determined to estimate the widths of un-erupted
      lower canine and premolars of both sides from a single measurement of the first
      premolar.

PMID- 16279825
TI  - Effects of preoperative ibuprofen and naproxen sodium on orthodontic pain.
AB  - Three experimental groups of 20 patients each, all of whom were to undergo fixed
      orthodontic treatment, were enrolled in this prospective study. Group 1 was given
      a placebo, group 2 was given 400 mg ibuprofen, and group 3 was given 550 mg
      naproxen sodium. All the patients received only one dose that was given one hour
      before archwire placement. All patients were asked to complete a questionnaire
      concerning the pain perceived after archwire placement. The questionnaire was in
      the form of a seven-page booklet that contained 100-mm horizontal Visual Analogue
      Scale on which the patient marked the degree of discomfort at the indicated time
      periods. The patients were instructed to make a check on the scale at each time
      interval to represent the perceived severity of pain during each of four
      activities, ie, chewing, biting, fitting back teeth together, and fitting front
      teeth together. Incidence and severity of pain were recorded by the patient at
      two hours, six hours, nighttime on the day of appointment, 24 hours after the
      appointment, and two days, three days, and seven days after bonding. The results
      revealed that patients taking 550 mg naproxen sodium one hour before archwire
      placement had significantly lower levels of pain at two hours, six hours, and
      nighttime after adjustment than patients taking placebo or ibuprofen. However,
      the use of additional postoperative doses was recommended to control orthodontic
      pain completely.

PMID- 16279827
TI  - Dental and alveolar arch widths in normal occlusion and Class III malocclusion.
AB  - The aim of this study was to compare the transverse dimensions of the dental
      arches and alveolar widths of Class III malocclusion group with a group of
      untreated normal occlusion subjects. This study was performed using measurements
      on dental casts of 150 normal occlusion (mean age, 21.6 +/- 2.6 years) and 100
      Class III malocclusion (mean age, 15.4 +/- 2.2 years) subjects. Independent
      samples t-test was applied for comparing the groups. The findings of this study
      indicated that the mandibular intercanine and intermolar alveolar widths were
      significantly larger in the Class Ill group when compared with the normal
      occlusion sample (P < .001). Maxillary interpremolar, intermolar widths and all
      maxillary alveolar width measurements were significantly narrower in the Class
      III group (P < .001). In addition, the lower canine and premolar alveolar width
      measurements were also statistically significantly larger in the normal occlusion
      group when compared with the Class III malocclusion group (P < .001). Subjects
      with Class III malocclusion tend to have the maxillary teeth inclined to the
      lingual and mandibular teeth inclined to the buccal direction because of the
      restriction of maxillary growth and development according to dental arch width
      measurements. Therefore, rapid maxillary expansion should be considered before or
      during the treatment of a Class III patient with or without face-mask therapy.

PMID- 16279828
TI  - Occlusal status in Asian male adults: prevalence and ethnic variation.
AB  - The purpose of this study was to determine the occlusal status in young Asian
      male adults of three ethnic groups. Study models of a sample of male army
      recruits (N = 339, age 17-22 years) with no history of orthodontic treatment were
      assessed. The ethnic proportions of the sample were Chinese 76.1% (n = 258),
      Malay 17.7% (n = 60), and Indian 6.2% (n = 21). British Standard Institute (BSI)
      and Angle's classification were used to determine incisor and molar
      relationships, respectively. Chi-square test or Fisher's Exact test was performed
      to compare the occlusal traits between ethnic groups. The distribution of incisor
      relationships of the total sample consisted of Class I = 48.1%, Class II/1 =
      26.3%, Class II/2 = 3.2%, and Class III = 22.4%. Right Angle's molar
      relationships were 49.9%, 24.5%, and 24.2% whereas left Angle's molar
      relationships were 53.1%, 25.1%, and 21.2% for Class I, II, and III,
      respectively. Comparison between ethnic groups found that Indian subjects were
      more likely to have Class II/1 malocclusions and clinically missing permanent
      teeth (P < .05). The study found that the overall prevalence of malocclusion
      (BSI) was Class I, Class II/1, Class III, and Class II/2 in descending order of
      proportions. Angle's Class I molar was most prevalent followed by Class II and
      Class III relations. A significant difference in occlusal status between the
      ethnic groups was found regarding incisor relationship and missing permanent
      teeth (P < .05).

PMID- 16279829
TI  - Cephalometric evaluation of maxillomandibular relationships in patients wearing
      complete dentures: a pilot study.
AB  - The purpose of this study was to evaluate the changes in vertical and sagittal
      maxillomandibular relationship of the patients who had been wearing dentures for
      an extensive period. Fifteen edentulous patients (seven men and eight women; mean
      age 63.5 years) who had worn dentures for six to 16 years (mean 10 years) were
      selected for this study. New prostheses were fabricated by conventional methods,
      and the patients were evaluated cephalometrically before and after the new
      prosthesis. The results were compared by Wilcoxon signed rank test (P < .05).
      Results indicated that a prognathic mandible and a pseudo Class III relationship
      with a reduced occlusal vertical dimension became a normal Class I
      maxillomandibular relation when the new prosthesis was inserted. A better facial
      profile was achieved.

PMID- 16279830
TI  - Orthodontic anchorage implants inserted in the median palatal suture and normal
      transverse maxillary growth in growing dogs: a biometric and radiographic study.
AB  - Small osseointegrated implants inserted in the palate provide a reliable
      anchorage control during orthodontic treatment. When these implants are inserted
      in the median palatal suture in growing individuals, the possible effects on
      normal transverse maxillary growth are still unknown. Therefore, the aim of this
      study was to evaluate the influence of orthodontic anchorage implants on
      transverse maxillary growth when inserted in the median palatal suture of growing
      dogs. Five growing dogs were used, one of them randomly selected as a control
      dog. The test dogs each received two implants in the median palatal suture.
      Impressions and occlusal radiographs of the upper jaws were taken at baseline
      (TO), after 84 days (T1), and at the end of the study after 168 days (T2).
      Measurements to compare increases in maxillary width between test dogs and
      control dog were performed on study casts and occlusal radiographs at TO, T1, and
      T2. Restricted transverse growth was observed in the test dogs in the canine
      region. Transverse growth in the region of second and fourth premolars was
      similar for the test dogs and the control dog. These results may be of some
      clinical relevance when orthodontic anchorage implants are to be inserted in
      growing individuals. An alternative insertion site, for example the parasagittal
      region, should be considered in these cases, to avoid possible negative effects
      on normal transverse maxillary development.

PMID- 16279831
TI  - Effect of changing a test parameter on the shear bond strength of orthodontic
      brackets.
AB  - The purpose of this study was to determine the effect of changing the crosshead
      speed of the testing machine on the shear bond strength of orthodontic brackets
      to enamel while standardizing all the other variables. Forty freshly extracted
      human molars were bonded using the Transbond XT adhesive system (3M Unitek,
      Monrovia, Calif). The teeth were randomly divided into two groups. In group I,
      the shear bond strength was measured at a crosshead speed of 5.0 mm/min, and in
      group II the shear bond strength was measured at a crosshead speed of 0.5 mm/
      min. Within half an hour from the initial bonding of each tooth, an
      occlusogingival load was applied to the bracket, producing a shear force at the
      bracket-tooth interface. This was accomplished by using the flattened end of a
      steel rod attached to the crosshead of a Universal Test Machine (Zwick GmbH & Co,
      Ulm, Germany). The t-test results (t = 2.71) indicated that there was a
      significant difference (P = .014) in the shear bond strengths between the group
      tested at a crosshead speed of 5.0 mm/min and the group tested at a crosshead
      speed of 0.5 mm/min. The mean shear bond strengths for the two groups were 7.0 +/
      4.6 MPa and 12.2 +/- 4.0 MPa, respectively. These findings indicated that it is
      important to identify the parameters included in shear bond testing in order to
      enable meaningful comparisons of the performance of different materials.

PMID- 16279832
TI  - Bond strength of disinfected metal and ceramic brackets: an in vitro study.
AB  - The aim of this in vitro investigation was to test whether disinfecting with
      Chlorhexamed fluid had an influence on the shear bond strength of metal and
      ceramic orthodontic brackets. Metal and ceramic brackets were fixed by the
      composite adhesives Transbond XT (light curing) and Concise (chemical curing) to
      224 bovine permanent mandibular incisors. Bovine teeth were divided into eight
      groups of 28 each as group 1: metal bracket/Transbond XT, group 2: disinfected
      metal bracket/Transbond XT, group 3: metal bracket/Concise, group 4: disinfected
      metal bracket/Concise, group 5: ceramic bracket/Transbond XT, group 6:
      disinfected ceramic bracket/Transbond XT, group 7: ceramic bracket/Concise, and
      group 8: disinfected ceramic bracket/Concise. Adhesive bonding was done according
      to the manufacturers' instructions. As shown by group comparison (Kruskal-Wallis
      test, univariate analysis of variance, P < .001), the disinfection of metal
      brackets had no statistically relevant influence on shear bond strength (P =
      .454). However, disinfecting ceramic brackets with either adhesive led to a
      significant reduction in shear bond strength compared with the untreated ceramic
      bracket group (P < .001). The Fisher's exact test of the Adhesive Remnant Index
      (ARI) scores showed a significant difference within the metal group bonded with
      different adhesives (P = .0003). The ARI scores 1 and 2 were not reached by the
      ceramic bracket groups. The disinfection of the ceramic brackets is a suitable
      procedure for clinical use because the measured shear bond strength values were
      higher than 6-8 MPa required in orthodontics.

PMID- 16279834
TI  - Class II correction in a severe hyperdivergent growth pattern, bilateral open
      bite and oral compromise.
AB  - Severe vertical growth pattern and open bites are frequent problems the
      orthodontist must resolve but require a proper diagnosis, treatment plan, timing,
      and mechanotherapy to be properly treated. A case report with these problems is
      presented.

PMID- 16279833
TI  - Effect of saliva contamiination on the shear bond strength of orthodontic
      brackets bonded with a self-etching primer.
AB  - This study evaluates the effect of saliva contamination at different stages of
      the bonding brackets procedure using the self-etching primer Adper Prompt L-Pop
      (3M ESPE, Minneapolis, Minn) and the resin orthodontic adhesive system Transbond
      XT (3M). A total of 70 brackets were bonded to human extracted premolars, which
      were divided into four groups: group 1, uncontaminated (control); group 2, saliva
      application before priming; group 3, saliva application after priming; and group
      4, saliva application before and after priming. Shear bond strength was measured
      with a universal test machine. The adhesive remnant on the tooth after debonding
      was determined using image analysis equipment. Significant differences were only
      observed between group 1 (12.42 +/- 3.27) and groups 2 (9.93 +/- 4.50) and 4
      (9.59 +/- 2.92) (P < .05). Concerning the adhesive remnant, no significant
      differences were found between the groups evaluated (P > .05).

PMID- 16279835
TI  - Early orthodontic treatment and long-term observation in a patient with Morquio
      syndrome.
AB  - Early orthodontic treatment and long-term observation in a patient with Morquio
      syndrome were demonstrated. To date, there are no case reports describing
      orthodontic treatment in such a patient. The patient showed spaced maxillary and
      mandibular arches with a tongue thrust habit at age seven years eight months. She
      also showed a protruded upper lip, labial inclination of the upper and lower
      anterior teeth, and thin enamel. The tongue thrust habit disappeared after the
      application of a removable orthodontic appliance. The spaced dentition in the
      upper and lower arches improved after treatment with a fixed appliance with
      closing loop arch wire (0.017 x 0.025") and bands on the upper and lower molars.
      We did not use an edgewise appliance because of the thin enamel. The protruded
      upper lip and labial inclination of the upper and lower anterior teeth were also
      improved after treatment, but optimal intercuspation of the teeth was not
      achieved. However, optimal intercuspation of the teeth was achieved after long
      term observation and the masticatory function was improved. It was suggested that
      early orthodontic treatment could improve the malocclusion in a patient with
      Morquio syndrome and that improvement of masticatory function could be achieved
      during a long-term retention period.

PMID- 16279838
TI  - Theta rhythms coordinate hippocampal-prefrontal interactions in a spatial memory
      task.
AB  - Decision-making requires the coordinated activity of diverse brain structures.
      For example, in maze-based tasks, the prefrontal cortex must integrate spatial
      information encoded in the hippocampus with mnemonic information concerning route
      and task rules in order to direct behavior appropriately. Using simultaneous
      tetrode recordings from CA1 of the rat hippocampus and medial prefrontal cortex,
      we show that correlated firing in the two structures is selectively enhanced
      during behavior that recruits spatial working memory, allowing the integration of
      hippocampal spatial information into a broader, decision-making network. The
      increased correlations are paralleled by enhanced coupling of the two structures
      in the 4- to 12-Hz theta-frequency range. Thus the coordination of theta rhythms
      may constitute a general mechanism through which the relative timing of disparate
      neural activities can be controlled, allowing specialized brain structures to
      both encode information independently and to interact selectively according to
      current behavioral demands.

PMID- 16279839
TI  - Systematic discovery of new recognition peptides mediating protein interaction
      networks.
AB  - Many aspects of cell signalling, trafficking, and targeting are governed by
      interactions between globular protein domains and short peptide segments. These
      domains often bind multiple peptides that share a common sequence pattern, or
      "linear motif" (e.g., SH3 binding to PxxP). Many domains are known, though
      comparatively few linear motifs have been discovered. Their short length (three
      to eight residues), and the fact that they often reside in disordered regions in
      proteins makes them difficult to detect through sequence comparison or
      experiment. Nevertheless, each new motif provides critical molecular details of
      how interaction networks are constructed, and can explain how one protein is able
      to bind to very different partners. Here we show that binding motifs can be
      detected using data from genome-scale interaction studies, and thus avoid the
      normally slow discovery process. Our approach based on motif over-representation
      in non-homologous sequences, rediscovers known motifs and predicts dozens of
      others. Direct binding experiments reveal that two predicted motifs are indeed
      protein-binding modules: a DxxDxxxD protein phosphatase 1 binding motif with a KD
      of 22 microM and a VxxxRxYS motif that binds Translin with a KD of 43 microM. We
      estimate that there are dozens or even hundreds of linear motifs yet to be
      discovered that will give molecular insight into protein networks and greatly
      illuminate cellular processes.

PMID- 16279842
TI  - The eventual pain and joy of grant writing.

PMID- 16279840
TI  - Persistent amyloidosis following suppression of Abeta production in a transgenic
      model of Alzheimer disease.
AB  - BACKGROUND: The proteases (secretases) that cleave amyloid-beta (Abeta) peptide
      from the amyloid precursor protein (APP) have been the focus of considerable
      investigation in the development of treatments for Alzheimer disease. The
      prediction has been that reducing Abeta production in the brain, even after the
      onset of clinical symptoms and the development of associated pathology, will
      facilitate the repair of damaged tissue and removal of amyloid lesions. However,
      no long-term studies using animal models of amyloid pathology have yet been
      performed to test this hypothesis. METHODS AND FINDINGS: We have generated a
      transgenic mouse model that genetically mimics the arrest of Abeta production
      expected from treatment with secretase inhibitors. These mice overexpress mutant
      APP from a vector that can be regulated by doxycycline. Under normal conditions,
      high-level expression of APP quickly induces fulminant amyloid pathology. We show
      that doxycycline administration inhibits transgenic APP expression by greater
      than 95% and reduces Abeta production to levels found in nontransgenic mice.
      Suppression of transgenic Abeta synthesis in this model abruptly halts the
      progression of amyloid pathology. However, formation and disaggregation of
      amyloid deposits appear to be in disequilibrium as the plaques require far longer
      to disperse than to assemble. Mice in which APP synthesis was suppressed for as
      long as 6 mo after the formation of Abeta deposits retain a considerable amyloid
      load, with little sign of active clearance. CONCLUSION: This study demonstrates
      that amyloid lesions in transgenic mice are highly stable structures in vivo that
      are slow to disaggregate. Our findings suggest that arresting Abeta production in
      patients with Alzheimer disease should halt the progression of pathology, but
      that early treatment may be imperative, as it appears that amyloid deposits, once
      formed, will require additional intervention to clear.

PMID- 16279843
TI  - The codon 620 single nucleotide polymorphism of the protein tyrosine phosphatase
      22 gene does not contribute to autoimmune thyroid disease susceptibility in the
      Japanese.
AB  - The etiology of the autoimmune thyroid diseases (AITDs), Graves' disease (GD),
      and Hashimoto's thyroiditis (HT) is largely unknown. However, genetic
      susceptibility is believed to play a major role. The lymphoid tyrosine
      phosphatase (LYP), encoded by the protein tyrosine phosphatase-22 (PTPN22) gene,
      is a powerful inhibitor of T cell activation. Recently, a single-nucleotide
      polymorphism (SNP), encoding a functional arginine to tryptophan residue change
      at PTPN22 codon 620 in Caucasians has been shown to be associated with GD and
      other autoimmune diseases. We have used a polymerase chain reaction (PCR)
      restriction fragment (XcmI) assay to examine genotypes at the codon 620
      polymorphism in 334 unrelated patients with AITD and 179 controls. None of the
      patients with AITD and controls had the tryptophan allele. These data suggest
      that the codon 620 polymorphism of the PTPN22 gene does not have a causal role
      for AITD in the Japanese. However, we cannot exclude the PTPN22 region as
      harboring another susceptibility locus for AITD in linkage disequilibrium with
      the Trp/Arg SNP.

PMID- 16279841
TI  - DC-SIGN induction in alveolar macrophages defines privileged target host cells
      for mycobacteria in patients with tuberculosis.
AB  - BACKGROUND: Interplays between Mycobacterium tuberculosis, the etiological agent
      of tuberculosis (TB) in human and host professional phagocytes, namely
      macrophages (Mphis) and dendritic cells (DCs), are central to immune protection
      against TB and to TB pathogenesis. We and others have recently shown that the C
      type lectin dendritic cell-specific intercellular adhesion molecule-3 grabbing
      nonintegrin (DC-SIGN; CD209) mediates important interactions between mycobacteria
      and human monocyte-derived DCs (MoDCs) in vitro. METHODS AND FINDINGS: In order
      to explore the possible role of DC-SIGN in M. tuberculosis infection in vivo, we
      have analysed DC-SIGN expression in broncho-alveolar lavage (BAL) cells from
      patients with TB (n = 40) or with other non-mycobacterial lung pathologies,
      namely asthma (n = 14) and sarcoidosis (n = 11), as well as from control
      individuals (n = 9). We show that in patients with TB, up to 70% of alveolar
      Mphis express DC-SIGN. By contrast, the lectin is barely detected in alveolar
      Mphis from all other individuals. Flow cytometry, RT-PCR, and enzyme-linked
      immunosorbent assay analyses of BAL-derived fluids and cells indicated that M.
      tuberculosis infection induces DC-SIGN expression in alveolar Mphis by a
      mechanism that is independent of Toll-like receptor-4, interleukin (IL)-4, and IL
      13. This mechanism most likely relies on the secretion of soluble host and/or
      mycobacterial factors that have yet to be identified, as both infected and
      uninfected bystander Mphis were found to express DC-SIGN in the presence of M.
      tuberculosis. Immunohistochemical examination of lung biopsy samples from
      patients with TB showed that the bacilli concentrate in pulmonary regions
      enriched in DC-SIGN-expressing alveolar Mphis in vivo. Ex vivo binding and
      inhibition of binding experiments further revealed that DC-SIGN-expressing
      alveolar Mphis constitute preferential target cells for M. tuberculosis, as
      compared to their DC-SIGN- counterparts. In contrast with what has been reported
      previously in MoDCs in vitro, ex vivo DC-SIGN ligation by mycobacterial products
      failed to induce IL-10 secretion by alveolar Mphis, and IL-10 was not detected in
      BALs from patients with TB. CONCLUSION: Altogether, our results provide further
      evidence for an important role of DC-SIGN during TB in humans. DC-SIGN induction
      in alveolar Mphis may have important consequences on lung colonization by the
      tubercle bacillus, and on pulmonary inflammatory and immune responses in the
      infected host.

PMID- 16279844
TI  - Association of CD40 gene polymorphism (C-1T) with susceptibility and phenotype of
      Graves' disease.
AB  - OBJECTIVE: Recently, a functional polymorphism in the CD40 gene at position -1, C
      to T change (C-1T) has been identified and the C/C genotype has been reported to
      be associated with Graves' disease (GD). DESIGN: We performed a case-control,
      replication study on 556 patients with GD and 611 healthy subjects in a Polish
      population. Furthermore, we analyzed the distribution of CD40 genotypes in
      subgroups of patients with GD divided according to age of onset, gender, family
      history, tobacco smoking, ophthalmopathy, and genetic parameters (CTLA4 49G,
      PTPN22/LYP 1858T or HLA-DRB1*03 alleles). RESULTS: Although the frequency of C/C
      genotype was increased in GD compared to controls, the difference was not
      significant (60.5% versus 55.8%, p = 0.062, odds ratio [OR] = 1.21, 95%
      confidence interval [CI]: 0.96-1.53). Because our study was underpowered to
      detect such a modest association, we performed a meta-analysis with the data from
      previous studies. The combined OR for the C/C genotype as a risk factor for GD
      was 1.22 (95% CI: 1.08-1.38, p = 0.001). We failed to find an interaction between
      CD40 genotypes and other GD susceptibility alleles. No significant genotype
      phenotype associations were found. CONCLUSIONS: Our results support the notion
      that CD40 C-1T polymorphism has a modest effect on genetic susceptibility to
      sporadic GD.

PMID- 16279845
TI  - Vitamin D receptor polymorphisms are associated with Graves' disease in German
      and Polish but not in Serbian patients.
AB  - Diverse genes are candidates for susceptibility to Graves' disease, including the
      vitamin D receptor (VDR), which regulates the transcription of target genes in
      response to the active metabolite 1,25(OH)(2)D(3). We analyzed four polymorphisms
      of the VDR gene (ApaI, TaqI, BsmI, and FokI) in patients with Graves' disease (n
      = 789) and healthy controls (n = 823) from three European populations (German,
      Polish, and Serbian). The VDR ApaI (rs7975232) and TaqI (rs731236) polymorphisms
      showed no significant difference in any population. The BsmI (rs1544410) variant
      "b" was associated with Graves' disease in the Polish population (p = 0.0070).
      The FokI (rs10735810) variant "f " was found to be associated with Graves'
      disease in Germans and "F" in Polish patients (p = 0.0024 and 0.0049,
      respectively). Construction of haplotypes for TaqI, ApaI, and BsmI showed the
      haplotype "Tab" to be the most frequent in the German and Polish population as
      well as in the Serbian patients, while "tAB" in Serbian controls. Our results
      show an association of VDR gene polymorphisms in the German and Polish population
      but not in the Serbian. Furthermore, the VDR polymorphisms are differentially
      distributed in the three populations. Therefore, VDR polymorphisms analysis needs
      to be stratified according to the population background.

PMID- 16279846
TI  - Expression of N-acetyl transferase human and human Arrest defective 1 proteins in
      thyroid neoplasms.
AB  - Protein acetylation is an important posttranslational modification regulating
      oncogenesis, apoptosis and cell cycle. NATH (N-acetyl transferase human) is
      overexpressed at the mRNA level in papillary thyroid carcinomas relative to non
      neoplastic thyroid tissue. The NATH protein has recently been demonstrated to be
      the partner of hARD1 (human Arrest defective 1) and this complex acetylates the N
      termini of proteins. ARD1 has also been implicated in the destabilization of the
      transcription factor HIF-1alpha (hypoxia inducible factor-1alpha). Using human
      thyroid papillary carcinoma biopsies and NATH- and hARD1-specific antibodies, we
      examined the levels of endogenous NATH and hARD1 proteins in 27 patients. We
      demonstrate that NATH protein level is upregulated in neoplastic versus non
      neoplastic tissue in good accordance with our previous mRNA findings. In all
      tumors in which NATH was downregulated compared to non-neoplastic tissue, the
      hARD1 protein level was concomitantly reduced. SiRNA-mediated knockdown of NATH
      resulted in decreased levels of hARD1 protein. Taken together, these results
      suggest that NATH positively affects the level of hARD1 protein both in vivo and
      in cell cultures.

PMID- 16279847
TI  - Disturbed expression of type 1 and type 2 iodothyronine deiodinase as well as
      titf1/nkx2-1 and pax-8 transcription factor genes in papillary thyroid cancer.
AB  - Type 1 and type 2 iodothyronine 5' deiodinases (D1 and D2, respectively) catalyze
      the conversion of thyroxine (T(4)) to triiodothyronine (T(3)). Similar to other
      genes crucial for T(3) generation, D1 and D2 expression might be disturbed in
      papillary thyroid cancer (PTC) possible as a result of impairments in thyroid
      transcription factors Titf1/Nkx2-1 and Pax-8. The aim of the study was to
      investigate changes in the expression of D1 and D2 in PTC compared to changes in
      the expression of Titf1/Nkx2-1 and Pax-8. Although D1 and D2 activities were
      decreased in tumor samples (PTC) compared to control C samples (tissues from a
      nontumorous part of the gland), the differences were not statistically
      significant. Contrary to that, their mRNA levels were significantly decreased in
      PTC samples compared to C samples (p = 0.017 and p = 0.012, respectively).
      Interestingly there was clear discrepancy between enzymatic activity and mRNA
      level of both deiodinases. There was a statistically significant correlation
      between D1 and Pax-8 (r = 0.464, p = 0.039), D2 and Pax-8 (r = 0.461, p = 0.041),
      D2 and Titf1/Nkx2-1 mRNA levels (r = 0.526, p = 0.017). Our results show that
      changes in D1 and D2 expression in PTC, including the discrepancy between
      deiodinases activity and mRNA level, might possibly related to impaired
      Titf1/Nkx2-1 and Pax-8 action.

PMID- 16279848
TI  - Thyroid hormone withdrawal in patients with differentiated thyroid carcinoma: a
      one hundred thirty-patient pilot survey on consequences of hypothyroidism and a
      pharmacoeconomic comparison to recombinant thyrotropin administration.
AB  - The study objective was to elucidate clinical, quality-of-life, and
      pharmacoeconomic effects of hypothyroidism secondary to thyroid hormone
      withdrawal (withdrawal) in athyroid patients with differentiated thyroid cancer
      (DTC). We also intended to compare societal costs of withdrawal and recombinant
      human thyroid-stimulating hormone administration (rhTSH) in this population. We
      mailed a 13-item pilot survey to patients with DTC who had undergone withdrawal
      before diagnostic whole-body scan (dxWBS). Using survey results and actual and
      estimated cost data, we retrospectively constructed a societal cost model
      comparing withdrawal versus rhTSH and performed a sensitivity analysis by
      increasing the conservatism of 8 assumptions about withdrawal costs. One hundred
      thirty (55%) of 236 patients answered the questionnaire. Among respondents, 92%
      had symptomatic and 85% multisymptomatic hypothyroidism. Almost half sought
      medical attention for hypothyroid complaints. Approximately one third drove motor
      vehicles while hypothyroid. Median absence from salaried work was 11 days per
      withdrawal. In the pharmacoeconomic model, societal costs per dxWBS were
      approximately 326 euro (25%) greater for withdrawal than for rhTSH. In the
      sensitivity analysis, societal costs of rhTSH exceeded those of withdrawal by
      approximately 307 euro (30%). In conclusion, hypothyroidism secondary to
      withdrawal causes important morbidity, safety risks, and productivity impairment.
      rhTSH avoids these drawbacks at roughly equivalent societal cost to that of
      withdrawal.

PMID- 16279849
TI  - Graves' disease with moderate-severe endocrine ophthalmopathy-long term results
      of a prospective, randomized study of total or subtotal thyroid resection.
AB  - The optimal thyroid surgery to be performed in patients with Graves' disease and
      concomitant endocrine ophthalmopathy is a matter of debate. We randomly assigned
      44 patients with moderate-severe eye signs in a trial of treatment with subtotal,
      leaving a small (approximately 2 g) thyroid remnant, or total thyroidectomy. At
      inclusion, the patients had been treated with antithyroid drugs, and
      corticosteroids been given to 12 (27%). All received postoperative thyroxine
      supplementation and were followed for 3 years at regular examinations. The eye
      disease improved in all cases, and throughout the study, the two groups did not
      differ with regard to subjective and objective eye symptoms and laboratory
      findings. At the study start, motility disturbances were present in 8 and 11 of
      the cases in the subtotal and total resection group and proptosis in 16 and 17,
      respectively. After 3 years, the corresponding data were 3 and 6 cases with
      motility defects and 16 and 15 cases with proptosis. Thyrotropin (TSH)-receptor
      antibody levels gradually fell and became nondetectable in 21 (49%). The surgical
      complication rate (permanent recurrent laryngeal nerve paresis and permanent
      hypoparathyroidism) was significantly higher in the total thyroidectomy group.
      The data indicate that in patients with Graves' disease and active endocrine
      ophthalmopathy, subtotal thyroidectomy, leaving a small thyroid remnant, will
      reduce the risk of surgical complications but not the beneficial effect of
      surgery.

PMID- 16279850
TI  - An assessment of urinary and breast milk iodine concentrations in lactating
      mothers from Gorgan, Iran, 2003.
AB  - Dietary iodine is essential for the production of thyroid hormones. Breast-fed
      infants are reliant on maternal iodine intake. The aim of this study was to
      evaluate iodine sufficiency in lactating women in Iran. The sample consisted of
      100 lactating mothers referred to the Taleghani Hospital of Gorgan, Iran. Goiter
      was graded according to World Health Organization (WHO) classification. Spot
      urine and breast-milk samples were collected for the measurement of iodine
      concentrations. Urine iodine concentrations (UIC) less than 100 and breast-milk
      iodine concentrations (MIC) less than 50 microg/L were considered consistent with
      iodine deficiency. Forty-three percent of women had grade 1 and 2 goiters,
      respectively. The median UIC was 259 microg/L. UIC was less than 100 in 16%.
      Grade 1 and 2 goiters were each present in 8% of mothers with UIC less than 100
      microg/L. The median MIC was 93.5 microg /L. MIC was less than 50 microg /L in
      19%. Grade 1 and 2 goiters were present in 11% and 8%, respectively, of women
      with MIC <50 mg/L. MIC and UIC levels were significantly correlated (r = 0.44, p
      < 0.0001). Iodine deficiency and goiter were associated (p < 0.0001). UIC and MIC
      concentrations are sufficient in Gorgan, Iran. However, individual infants remain
      at risk for low iodine intake via breast milk.

PMID- 16279851
TI  - Interobserver variation for ultrasound determination of thyroid nodule volumes.
AB  - Thyroid ultrasound is used in the routine clinical assessment and the follow-up
      of thyroid disorders. The follow- up of patients with thyroid nodules is mostly
      based on thyroid nodule volume determinations performed by different observers.
      However, for the judgment of treatment effects there is uncertainty about the
      interobserver variation of thyroid nodule volume measurements by ultrasound
      because there are no prospective blinded studies available comparing the
      interobserver variation in thyroid nodule volume measurement. The aim of our
      study was therefore to determine the variation of thyroid nodule volume
      determinations for different observers. We conducted a prospective blinded trial.
      Our study population consisted of 42 probands (8 men, 34 women) with an uniform
      distribution of thyroid nodule sizes (25 uninodular and 17 multinodular thyroid
      glands). We compared the results of 3 ultrasonographers with certified experience
      in thyroid ultrasound. The interobserver variation for the determination of
      thyroid nodule volume (n = 38) was 48.96% for the ellipsoid method and 48.64% for
      the planimetric method. The interobserver variation for determining thyroid
      volume (n = 40) was 23.69% for the ellipsoid method and 17.82% for the
      planimetric method. A regression analysis revealed that the probability for the
      identification of the same nodule in nodular thyroids by all sonographers is 90%,
      if the nodule is at least 15mm in greatest diameter. Future investigations should
      not describe changes in nodule volume less than 50% as therapy effects because
      only volume changes of at least 49% or more can be interpreted as nodule
      shrinkage or growth. Reporting of nodule volume modification 50% or more and lack
      of information for ultrasound procedures introduce a bias in studies evaluating
      the effects of nodule treatments. The clinical interpretation of a
      shrinking/growing thyroid nodule based on volume determinations by ultrasound is
      not well established because it is difficult to reproduce a two-dimensional image
      plane for follow-up studies.

PMID- 16279852
TI  - Postpartum thyroiditis: long-term follow-up.
AB  - OBJECTIVE: To determine the incidence of persistent hypothyroidism (PH) after a
      long follow-up in 45 patients with postpartum thyroiditis (PPT) from a
      nonselected population of 641 pregnant women (PPT incidence 7.8%) and the
      clinical and biochemical factors associated with PPT evolution. DESIGN AND
      PATIENTS: The 45 women who developed PPT were followed for 8.1 +/- 2.2 years
      after delivery. MEASUREMENTS: Age at delivery, family and personal history,
      smoking, newborn gender, breast-feeding, and PPT course were recorded.
      Thyrotropin (TSH) and free thyroxine (T(4)) concentrations and antithyroid
      antibodies were evaluated at each visit. PH was considered when it persisted one
      year after being diagnosed. RESULTS: Fourteen of 45 patients with PPT developed
      PH with a probability of 56% after a PPT episode with hypothyroidism. None of the
      patients who developed hyperthyroidism alone during PPT evolved to PH. PH risk
      was higher if the newborn was a girl (relative risk [RR] 3.88) and increased for
      each additional TSH unit during PPT and for every additional year of the mother's
      age. CONCLUSIONS: The probability of developing PH after a PPT with
      hypothyroidism episode is 56%. PPT screening in all women permits us to establish
      levothyroxine treatment, if necessary, before a new pregnancy.

PMID- 16279853
TI  - Acute suppurative thyroiditis after fine-needle aspiration causing
      thyrotoxicosis.
AB  - A case of thyrotoxicosis caused by acute suppurative thyroiditis after repeated
      fine-needle aspiration (FNA) is described. A 39-year-old woman with atopic
      dermatitis showed rapid enlargement of a left thyroid cyst after a third FNA. She
      had a high fever, painful swelling of the left thyroid, and elevated thyroid
      hormone levels. Ultrasonography revealed abscess formation in the left thyroid
      cyst. The cytologic examination of an FNA specimen showed abundant neutrophils,
      and culture of the aspirate yielded Staphylococcus aureus. Because antibiotic
      treatment for 1 month failed to improve the inflammatory findings, the patient
      subsequently underwent left thyroid lobectomy, which resulted in the
      normalization of thyroid function and the resolution of inflammation. Thyroid
      infection had possibly been induced by needle-track seeding, because atopic skin
      favors colonization by S. aureus because of local immunologic deficiency. FNA is
      a useful and safe technique for aspirating fluid from thyroid cysts, but special
      care is required in patients with atopic dermatatis to avoid bacterial infection.

PMID- 16279854
TI  - Atypical subacute thyroiditis caused by Epstein-Barr virus infection in a three
      year-old girl.
AB  - Subacute thyroiditis is a rare disease in childhood and is considered postviral
      in origin. Epstein-Barr virus (EBV) involvement has been suspected, but just once
      demonstrated in an adult female. We report a case of subacute thyroiditis during
      infectious mononucleosis in a 3-year-old girl. The diagnosis of infectious
      mononucleosis was supported, in addition to the typical clinical symptoms, by
      presence of EBV DNA both in plasma and leukocytes. Subacute thyroiditis was
      diagnosed based on elevated thyroid hormone levels with thyrotropin (TSH)
      suppression, high inflammation markers and almost absent (99)TC uptake by
      thyroid. Moreover after 3 months from diagnosis thyroid function went back to
      normal as well as the (99)TC uptake.

PMID- 16279856
TI  - Acute respiratory failure with cervically located benign cystic thyroid mass.

PMID- 16279855
TI  - Autoimmune thyroiditis associated with autoimmune hepatitis.

PMID- 16279857
TI  - Cavernous hemangioma of the thyroid.

PMID- 16279858
TI  - Withdrawal of the parenterally applicable form of thyrostatic drugs in Austria.

PMID- 16279862
TI  - Treatment of bipolar mania with atypical antipsychotics.
AB  - Acute manic episodes in bipolar disorder require rapid and effective relief.
      Pharmacotherapy has traditionally involved mood stabilizers such as lithium or
      divalproex. Evidence for the efficacy of atypical antipsychotics to treat bipolar
      mania, either as monotherapy or in combination with traditional mood-stabilizing
      agents, has increased in recent years. Since the combination of an atypical agent
      and a traditional mood stabilizer is generally well tolerated, it represents a
      first-line approach for the treatment of severe and treatment-resistant mania.
      Atypical antipsychotics have a superior neurological tolerability profile
      compared with typical antipsychotics and are preferentially recommended in most
      treatment guidelines. The atypical agents, olanzapine, risperidone, quetiapine,
      ziprasidone and aripiprazole, have demonstrated efficacy in bipolar mania in
      large randomized, controlled studies, and offer efficacy across a broader range
      of symptoms than typical antipsychotics, and may even have mood-stabilizing
      properties traditionally associated with lithium and divalproex. Olanzapine,
      risperidone and quetiapine have been shown to be effective for manic episodes
      both as monotherapy and in combination with other agents such as lithium and
      divalproex. Although the tolerability profiles of atypicals as a class are
      superior to those of conventional antipsychotics, there are differences among the
      atypical agents in their propensity to cause certain adverse events such as
      extrapyramidal symptoms (EPS) and weight gain, particularly in the long-term. The
      ultimate choice of the atypical agent will depend on the patient's individual
      needs, but atypical antipsychotics are clinically effective options for achieving
      mood stabilization in the treatment of acute bipolar mania.

PMID- 16279863
TI  - Bipolar depression: the role of atypical antipsychotics.
AB  - Acute manic episodes in bipolar disorder require rapid and effective relief.
      Bipolar depression is a major component of the bipolar disorder spectrum.
      Existing treatment options for bipolar depression include lithium, lamotrigine
      and conventional antidepressants. However, lithium is more effective in treating
      mania or hypomania than depression, both acutely and prophylactically,
      lamotrigine has only been demonstrated to be effective in one adequately powered
      study in acute bipolar I depression, and conventional antidepressants have been
      associated with emergent mania and cycle acceleration. Symptomatic outpatients
      can expect to spend, on average, 33% of their time in the depressive phase
      compared with 11% in the manic phase. Consequently, there is a need for
      additional agents to effectively treat bipolar depression. The atypical agents
      olanzapine, risperidone and quetiapine have demonstrated efficacy against the
      manic phase of bipolar disorder and appear also to have potential in the
      depressive phase. Olanzapine monotherapy significantly improved depressive
      symptoms compared with placebo in patients with bipolar disorder in an 8-week
      randomized, controlled clinical study, but the magnitude of the clinical effect
      was small. The observed improvement in depressive symptoms became moderately
      large when olanzapine was combined with the antidepressant fluoxetine. Quetiapine
      monotherapy also resulted in significant improvements compared with placebo in
      patients with either bipolar I or bipolar II disorder in another 8-week
      randomized, controlled clinical study, but the effect size was large. A 6-month
      open-label study of risperidone added to ongoing therapy demonstrated
      improvements in depressive symptoms in patients with bipolar and schizoaffective
      disorders experiencing a manic, hypomanic, mixed or depressive episode. The
      receptor-binding profile of these agents supports a role in the treatment of
      depressive symptoms and clinical data are beginning to emerge of their efficacy
      in both the acute and maintenance setting.

PMID- 16279864
TI  - The bipolar spectrum: diagnostic and pharmacologic considerations.
AB  - Bipolar disorder represents a clinically challenging, episodic, lifelong medical
      illness that is both disabling and dangerous to the patient and is associated
      with a high risk of suicide. The prognosis for bipolar patients is likely to
      worsen with delays in accurate diagnosis and treatment as time is allowed for
      more extensive complications and morbidity to accrue and for alcohol or other
      substance use comorbidity to complicate the course of the illness. Physicians
      face several challenges when diagnosing bipolar disorder, including overlapping
      symptomatology and comorbidity with other disorders, as well as the somewhat
      restrictive and categorical approach taken by the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition (DSM-IV) and the International
      Statistical Classification of Diseases, 10th Revision (ICD-10) diagnostic
      criteria. As a result, bipolar disorder is frequently unrecognized and
      misdiagnosed with considerable clinical and prognostic consequences for the
      patient. The accuracy of diagnosis of bipolar disorder could be improved through
      the introduction of a refined procedure for the identification and evaluation of
      a broader range of symptoms, and by careful attention to the presence of
      subthreshold symptomatology. A conceptual shift toward acceptance of a 'spectrum'
      model of bipolar disorder and the development of appropriate clinical diagnostic
      tools should assist physicians in differentiating bipolar disorder from other
      Axis I, Axis II, and personality disorders, as well as ensuring early diagnosis
      and therapeutic intervention.

PMID- 16279865
TI  - Maintenance therapy for bipolar disorder: current and future management options.
AB  - Bipolar disorder is an episodic condition usually requiring long-term, often life
      long, treatment to control acute symptoms and stabilize mood. Clinicians face
      several challenges when deciding on the most appropriate long-term management
      strategy for patients with bipolar disorder, and consideration must be given to
      the heterogeneity of symptoms, tolerability and patient acceptability as well as
      individual history of response. Numerous treatments are available for the
      management of bipolar disorder, including lithium, divalproex, conventional
      antipsychotics, the anticonvulsant lamotrigine, and several newer atypical
      agents, including olanzapine, risperidone, quetiapine, ziprasidone and
      aripiprazole. Antidepressants may also have a role in managing acute depressive
      episodes but are not recommended as monotherapy in either acute or long-term
      maintenance treatment. Studies suggest that pharmacologic treatment given in
      conjunction with cognitive therapy or group psychoeducation is superior to usual
      care. This article reviews current treatment options and management strategies
      for the long-term maintenance of health in patients with bipolar disorder.
      Particular emphasis is given to the atypical agents and psychosocial strategies
      aimed at optimizing treatment adherence and long-term outcomes.

PMID- 16279866
TI  - Living with bipolar disorder.
AB  - Bipolar disorder is a chronic, episodic disease characterized by intermittent
      episodes of depressive and manic symptoms. It causes significant and long-lasting
      distress, functional impairment and morbidity, and is associated with a high risk
      of mortality. Quality of life and disease burden, particularly in terms of
      lifestyle and general functioning, are gaining increasing recognition as valid
      therapeutic targets for intervention. Quality of life among patients with bipolar
      disorders is significantly impaired both during and between acute episodes.
      Somatic and mood symptoms, stigmatization, comorbid conditions, associated
      cognitive deficits and the burden of treatment all can combine to severely
      undermine patient quality of life and functioning at all levels. The tolerability
      of treatment is an important consideration when choosing a therapeutic option as
      patient satisfaction with, and adherence to, treatment can influence health
      outcomes and quality of life. Early intervention with the appropriate treatment
      can alter the course of bipolar disorder and improve the long-term experience of
      patients in their management of the disease.

PMID- 16279867
TI  - Identification of a short form of ubiquitin-specific protease 3 that is a
      repressor of rat glutathione S-transferase gene expression.
AB  - The transcription rate and protein expression from both GSTA2 (glutathione S
      transferase A2) and albumin genes decrease in rat liver after IL-6 (interleukin
      6) plus DEX (dexamethasone) treatment of primary hepatocytes or after LPS
      (lipopolysaccharide)-induced acute-phase response in animals. The down-regulation
      is associated with the induced expression of a nuclear protein (termed IL6DEX-NP
      for IL-6/DEX-induced nuclear protein) that binds to a specific site on the
      promoter of GSTA2, leading to a decrease in transcriptional activity. IL6DEX-NP
      is not similar to other transcription factors, and, for identification, we
      functionally cloned it from a rat liver library using a yeast one-hybrid screen
      based on DNA-binding activity. The cloned sequence was a truncated form of USP3
      (ubiquitin-specific protease 3) and the truncated USP3 protein in a yeast extract
      bound to DNA containing the IL6DEX-NP recognition sequence. Using 5'- and 3'-RACE
      (rapid amplification of cDNA ends), the complete sequence of USP3 was found in
      liver from LPS-treated rats. However, using Western blot analysis, only truncated
      forms of USP3 could be identified in nuclear extracts from LPS-treated rat
      livers. A GSTA2 promoter-reporter gene plasmid and USP3-expressing plasmids were
      transfected into rat hepatoma cells. Expression of the short form of USP3, but
      not the full-length protein, abolished expression from the reporter gene.
      Chromatin immunoprecipitation localized USP3 to the GSTA2 promoter in rat
      hepatocytes in vivo. We believe that the short form of USP3 is IL6DEX-NP and that
      it may play an important role in the negative regulation of proteins during the
      acute-phase response.

PMID- 16279868
TI  - Register now: validity later.

PMID- 16279869
TI  - Administrative registers in psychiatric research: a systematic review of validity
      studies.
AB  - OBJECTIVE: To conduct a systematic review of studies investigating the validity
      of administrative registers for use in psychiatric research. METHOD: Studies were
      identified using MEDLINE (1966-2004) and EMBASE (1980-2004) databases using
      keywords 'validity' or 'reliability' combined with 'register' or 'database$'.
      Studies reviewed by two raters blind to each other and quality assessed using a
      data extraction form devised by the authors. A narrative description of the
      findings is presented. RESULTS: Fourteen studies were identified, seven of which
      concerned Scandinavian registers. Ten studies were solely concerned with
      diagnostic validity and the most common single diagnosis studied was
      schizophrenia (five studies). Methods used and study quality varied widely.
      CONCLUSION: Given the importance of the area, relatively little high-quality work
      exists into systematically measuring the diagnostic data validity of registers
      for research purposes.

PMID- 16279870
TI  - Labour force activity by people with depression and anxiety disorders: a
      population-level second-order analysis.
AB  - OBJECTIVE: To identify the population-level first- and second-order effects among
      candidate correlates of labour force activity by people with ICD-10 depression
      and anxiety disorders. METHOD: Australian Bureau of Statistics multistage
      sampling strategies obtained a household sample of 37,580 individuals. Analyses
      were conducted using multiple binary logistic regression. RESULTS: The impact of
      depression and anxiety on labour force activity depended on the extent of
      employment restrictions, age and country of birth. Background second-order
      effects help explain labour force participation and employment in the wider and
      predominantly healthy community. A significantly greater proportion of those
      receiving mental health treatment for anxiety and depression were not in the
      labour force. CONCLUSION: These second-order effects reveal the substantial
      impact of depression and anxiety disorders on labour force activity across the
      working life. Those with more severe employment restrictions appear to need more
      intensive and continuous forms of assistance.

PMID- 16279871
TI  - Factors associated with chronic depressive episodes: a preliminary report from
      the STAR-D project.
AB  - OBJECTIVE: To identify baseline sociodemographic and clinical factors associated
      with a current chronic major depressive episode (MDE). METHOD: Outpatients with
      major depressive disorder enrolled in 41 US primary or psychiatric care sites
      were divided into two groups based on self-report of current episode length (<24
      or > or =24 months). Logistic regression models were used to identify factors
      associated with chronicity of current depressive episode. RESULTS: About 21.2% of
      1380 subjects were in current, chronic MDEs. Older age, less education, lower
      income, no private insurance, unemployment, greater general medical illness
      burden, lower physical quality of life, concurrent generalized anxiety disorder,
      fewer prior episodes, and history of prior suicide attempts were all associated
      with chronic episodes. Blacks, Hispanics, and patients receiving care in primary
      as opposed to psychiatric care settings exhibited greater chronicity. CONCLUSION:
      Chronic depressive episodes are common and are associated with greater illness
      burden, comorbidity, socioeconomic disadvantage, and racial/ethnic minority
      status.

PMID- 16279872
TI  - Cortisol level predicts executive and memory function in depression, symptom
      level predicts psychomotor speed.
AB  - OBJECTIVE: On a group level depression is related to hypercortisolism and to
      psychomotor retardation, executive dysfunction and memory impairment. However,
      intra-group heterogeneity is substantial. Why some are impaired while others
      remain in the normal range, is not clear. The present study aims at discerning
      the relative contribution of present symptom severity and hypercortisolism to
      impairment in the three domains of cognition. METHOD: Morning saliva cortisol was
      measured in 26 subjects with recurrent major depression prior to a
      neuropsychological examination with tests known to be sensitive to cognitive
      impairment in depression. RESULTS: Cortisol level correlated with executive
      dysfunction and post-encoding memory deficits, but not with processing speed.
      Depression level correlated with processing speed. These patterns remained
      significant after controlling for confounders through partial correlations.
      CONCLUSION: The association between cortisol and cognition is not an artifact of
      psychiatric symptom load. High level of saliva cortisol is associated with
      aspects of cognition that can be dissociated from psychomotor retardation, which
      is dependent on symptom load.

PMID- 16279873
TI  - Suicide trends following the Taiwan earthquake of 1999: empirical evidence and
      policy implications.
AB  - OBJECTIVE: Mental health impact of severe earthquakes on survivors has attracted
      considerable attention. Suicide represents a terminal outcome of the spectrum of
      potential major mental health issues spawned by severe earthquakes. This study
      used time-series analysis to examine the time trends of increased suicide rates
      after the Chi-Chi earthquake of 1999 in Taiwan in the affected counties. METHOD:
      Adult cause of death data were used to study monthly suicide rates per 100,000
      adult population in the study and control counties, during January 1995 to
      December 2001. Box and Tiao's event intervention analysis was used to examine
      changes in monthly suicide rates before and after the Chi-Chi earthquake.
      RESULTS: During the post-quake period, October 1999 to December 2001, the mean
      monthly suicide rate in the affected counties was 1.567 per 100,000, compared
      with the control counties' rate of 1.297 per 100,000. Mean monthly suicide rate
      among the high-exposure group was 42% higher during the 26 months following the
      earthquake than the average for the entire observation period. Examined by time
      trends, the increased suicide rate registered in the first month following the
      quake began a monthly gradual decline by 0.7/100,000 thereafter, accounting for a
      total reduction of 98% in quake-related suicides by the end of 10 months. Suicide
      rates fell to the baseline level after 10 months. CONCLUSION: We found that the
      mean monthly suicide rate for earthquake victims was higher while the low
      exposure group remained stable and consistent throughout the observation period,
      indicating that the impact on the high-exposure group was attributable to the
      earthquake. This indicates the need for providing strengthened psychiatric
      services during the first year following major disasters.

PMID- 16279875
TI  - Eleven-year clinical outcome of schizophrenia in Bali.
AB  - OBJECTIVE: To contrast the short-term and long-term outcome of schizophrenia in
      Bali. METHOD: The clinical outcomes of 46 schizophrenic patients (DSM-IV-TR)
      consecutively admitted to Bangli Mental Hospital were evaluated by Positive and
      Negative Syndrome Scale (PANSS) and Eguma's Social Adjustment Scale (ESAS) at a
      11-year follow-up, which was subsequent to a 5-year follow-up. RESULTS: Neither
      the PANSS score nor the ESAS score were significantly different, and there was a
      significant correlation between the two follow-up data. Subjects categorized into
      either the best or worst outcome group at the 5-year follow-up tended to be
      classified into the same category at the 11-year follow-up more often than those
      who were categorized into the medium outcome groups at the 5-year follow-up.
      CONCLUSION: The 5-year outcome of schizophrenia strongly predicted the 11-year
      outcome, especially for subjects who had gone into either a remissive or severe
      deterioration state within 5 years.

PMID- 16279874
TI  - Early insight predicts depression and attempted suicide after 4 years in first
      episode schizophrenia and schizophreniform disorder.
AB  - OBJECTIVE: To map the development of insight in the 4 years after presentation
      with first-episode schizophrenia and schizophreniform disorder and to determine
      the effects of evolving insight on depression and the likelihood of attempted
      suicide. METHOD: We assessed 101 individuals at presentation, 6 months and 4
      years. We measured insight, including recognition of mental illness, recognition
      of need for treatment and ability to relabel psychotic symptoms. We measured
      depression and recorded all suicide attempts. RESULTS: Insight improved with
      time. Recognition of mental illness at 6 months predicted depression and
      attempted suicide at 4 years. CONCLUSION: Six months after presentation, the
      greater the acknowledgement by people that they had a mental illness, the more
      depressed they were at 4 years and the greater the likelihood that they would
      attempt suicide by 4 years. This may have implications for disclosure of
      diagnosis.

PMID- 16279876
TI  - Neuropsychiatric symptoms in patients with multiple sclerosis.
AB  - OBJECTIVE: To explore the range of psychiatric symptoms in patients with multiple
      sclerosis (MS) and their association with neurological disability. METHOD:
      Patients diagnosed with MS during 1998-2000 in Rogaland and Hordaland counties,
      western Norway, were included. Psychiatric symptoms were assessed by the
      Neuropsychiatric Inventory (NPI). Patients with systemic lupus erythematosus
      (SLE) served as controls. RESULTS: Eighty-six of 93 eligible MS patients were
      included, and 80% showed at least one psychiatric symptom. The most frequent
      symptoms were depression (59%), sleep disturbance (48%), irritability/emotional
      lability (42%), and apathy (31%). Depression was associated with higher
      disability score. MS patients showed significantly higher NPI irritability score
      (P = 0.002), appetite disturbance score (P < 0.001), and apathy score (P = 0.01)
      than SLE patients. CONCLUSION: Neuropsychiatric symptoms occur frequently in
      patients with MS. Irritability and apathy are independent of disability and
      chronic disease and represent unique disease manifestations.

PMID- 16279877
TI  - Reducing the duration of untreated first-episode psychosis -- effects on baseline
      social functioning and quality of life.
AB  - OBJECTIVE: Long duration of untreated psychosis (DUP) is associated with poorer
      outcome. The TIPS study demonstrated that DUP can be reduced through early
      detection (ED). As quality of life (QoL) is associated with DUP it is expected
      that reduction of DUP leads to better QoL. METHOD: Consecutive first-episode
      patients with a DSM-IV diagnosis of non-organic, non-affective psychosis were
      included, 281 patients gave informed consent and 263 completed a full evaluation
      of QoL. RESULTS: There were no differences in subjective QoL between ED and No-ED
      groups attributable to reduction in DUP. There were significant bivariate
      differences in frequency of family and social contacts in favor of the ED group,
      but multivariate analyses indicated that these differences were based on
      differences in sample characteristics. CONCLUSION: Deterioration in QoL may
      precede overt symptom formation. Focus on functional loss in ED educational
      campaigns may identify risk subjects earlier in the course of the disorder.

PMID- 16279878
TI  - Internet forums: a self-help approach for individuals with schizophrenia?
AB  - OBJECTIVE: To study if and how online self-help forums for individuals with
      schizophrenia are used. METHOD: We analysed 1200 postings of 576 users in 12
      international schizophrenia forums regarding communicative skills [fields of
      interest and self-help mechanisms (SHM)]. RESULTS: The forums were predominantly
      used by affected individuals, few relatives or friends. The fields of interest of
      the users concern daily problems of the illness like symptoms and emotional
      involvement with the illness. Self-help mechanisms mostly used are disclosure and
      providing information. Emotional interaction e.g. empathy or gratitude were
      comparatively rare. CONCLUSION: Individuals suffering from schizophrenia
      participate in online self-help forums using the same SHM, discussing similar
      topics as do individuals with other psychiatric disorders as well as not affected
      relatives and caregivers. Therefore, this tool seems to be a useful approach to
      cope with alienation and isolation, albeit only a small number of schizophrenia
      forums are found in the Internet.

PMID- 16279879
TI  - Tuberculous meningitis masked by delirium in an alcohol-dependent patient: a case
      report.
AB  - OBJECTIVE: Patients with alcohol dependence syndrome can present with delirium
      which will mask underlying organic causes for the delirium. However, other
      medical diseases can also present with similar symptoms and should not be missed.
      The issues related to differentiating the different causes of delirium are
      briefly discussed. We describe a case of tuberculous meningitis in a patient with
      history of alcohol dependence who presented with delirium. METHOD: A case report.
      RESULTS: A 38-year-old male was admitted with history of irrelevant talk and
      abnormal behaviour of 2-month duration. He was also disoriented and his short
      term memory was impaired. He reported visual hallucinations. He had history of
      alcohol dependence of 5 years. A detailed mental status examination and
      neurological workup revealed an organic psychosis. CT scan showed a hypodense
      lesion suggestive of a tuberculoma. The cerebrospinal fluid findings were
      corroborative. He responded to antituberculous drugs which he took for one and a
      half years and recovered completely. He also underwent group therapy for his
      alcohol dependence and has since then refrained from alcohol intake. Currently he
      has gone back to his work as a car mechanic. CONCLUSION: We have highlighted the
      need for diagnosing and investigating carefully the cause of delirium in a
      patient with alcohol dependence syndrome. This shows that other curable causes of
      delirium must also be investigated in patients with alcohol dependence.

PMID- 16279883
TI  - Pro: Computerized tomographic fine needle aspiration (CT-FNA) is valuable in the
      management of infected pancreatic necrosis.

PMID- 16279885
TI  - Con: Computerized tomographic aspiration of infected pancreatic necrosis: the
      opinion against its routine use.

PMID- 16279886
TI  - A candidate's approach to a successful partnership.

PMID- 16279887
TI  - Endoscopic ampullectomy.

PMID- 16279888
TI  - Performance, tolerability, and symptoms related to prolonged pH monitoring using
      the Bravo system in Mexico.
AB  - BACKGROUND: The traditional system for esophageal 24-h pH monitoring requires
      transnasal introduction of the catheter with pH sensors; this technique produces
      discomfort, inconvenience, and interference with daily activity. Recently, a
      catheter-free pH monitoring system (Bravo) has been proposed as an alternative
      and promising method for 24-h pH. AIM: To evaluate performance, tolerability, and
      symptoms related to this new technology in our population. METHODS: Consecutive
      patients with gastroesophageal reflux disease (GERD) with indication for 24-h pH
      were included. pH Bravo capsule was placed 6 cm above the squamocolumnar junction
      using endoscopic measurement. Symptoms associated were evaluated daily in a
      personal diary until 7 days after the capsule attachment. Severity of symptoms
      was assessed by a 5-point Likert scale. Capsule detachment was assessed by chest
      X-ray. RESULTS: Eighty-four patients were included. Forty-nine were female (mean
      age 44 +/- 12 yr). Indications for pH monitoring were: nonresponse to proton pump
      inhibitor therapy in 38 (45%), preoperative evaluation for anti-reflux surgery in
      36 (43%), previous failed transnasal 24-h pH monitoring in 6 (7%), and extra
      esophageal manifestations of GERD in 4 (5%). The capsule was successfully
      attached in 95% of patients. At day 7, capsule detachment occurred spontaneously
      in all cases. Symptoms related to capsule attachment were: chest pain in 26
      (33%), foreign body sensation in 11 (14%), nausea in 5 (6%), and 9 (11%) patients
      had more than one symptom. Severities of those symptoms were mild, and no patient
      required removal of the capsule. Women and younger patients had more symptoms
      related to the procedure (p < 0.05). CONCLUSIONS: Esophageal pH monitoring with
      Bravo capsule is a safe, reliable, and tolerable method in patients with GERD.

PMID- 16279889
TI  - A prospective randomized trial of esomeprazole- versus pantoprazole-based triple
      therapy for Helicobacter pylori eradication.
AB  - OBJECTIVE: This prospective, randomized, controlled, head-to-head study was
      conducted to compare the efficacies of esomeprazole- and pantoprazole-based
      triple therapies for Helicobacter pylori eradication. METHODS: From January 2002
      to October 2003, 200 H. pylori-infected patients were randomly assigned to
      undergo twice daily treatment with esomeprazole 40 mg (n = 100) or pantoprazole
      40 mg (n = 100) combined with clarithromycin 500 mg and amoxicillin 1 g for 1 wk
      (ECA and PCA groups, respectively). Follow-up endoscopy was performed at 8 wks
      after the end of treatment to assess the treatment response. RESULTS: Intention
      to-treat analysis demonstrated a significantly higher eradication rate for the
      ECA group than for the PCA group (94%vs 82%, respectively, p= 0.009). Per
      protocol analysis also showed similar results (97%vs 84%, p= 0.003). Both groups
      had similar frequencies of adverse events (15%vs 24%) and drug compliance (97%vs
      96%). Multivariate analysis disclosed that the use of esomeprazole (OR: 1.56, 95%
      CI, 1.11-2.19) and good compliance 7.39 (95% CI, 1.27-42.95) were independent
      predictors of treatment success. Alcohol drinking was an independent predictor of
      eradication failure (OR: 0.18; 95% CI, 0.06-0.54). CONCLUSION: Esomeprazole-based
      triple therapy demonstrated a higher eradication rate than pantoprazole-based
      regimen. The differences in eradiation efficacies between the two study groups
      may be related to the more powerful acid inhibition effect and stronger anti-H.
      pylori activity of esomeprazole compared to pantoprazole.

PMID- 16279890
TI  - Helicobacter pylori: factors affecting eradication and recurrence.
AB  - Proton pump inhibitors play an important role in increasing the bioavailability
      of antibiotics in the gastric mucus by altering gastric volumes and increasing
      the stability of some antibiotics, e.g., clarithromycin. Increasing the doses of
      potent proton pump inhibitors has small effects on eradication rates but there
      may be differences between proton pump inhibitors that need further study.

PMID- 16279891
TI  - Urgent colonoscopy for evaluation and management of acute lower gastrointestinal
      hemorrhage: a randomized controlled trial.
AB  - OBJECTIVES: We hypothesized that early intervention in patients with lower
      gastrointestinal bleeding (LGIB) would improve outcomes and therefore conducted a
      prospective randomized study comparing urgent colonoscopy to standard care.
      METHODS: Consecutive patients presenting with LGIB without upper or anorectal
      bleeding sources were randomized to urgent purge preparation followed immediately
      by colonoscopy or a standard care algorithm based on angiographic intervention
      and expectant colonoscopy. RESULTS: A total of 50 patients were randomized to
      each group. A definite source of bleeding was found more often in urgent
      colonoscopy patients (diverticula, 13; angioectasia, 4; colitis, 4) than in the
      standard care group (diverticula, 8; colitis, 3) (the odds ratio for the
      difference among the groups was 2.6; 95% CI 1.1-6.2). In the urgent colonoscopy
      group, 17 patients received endoscopic therapy; in the standard care group, 10
      patients had angiographic hemostasis. There was no difference in outcomes among
      the two groups-including: mortality 2%versus 4%, hospital stay 5.8 versus 6.6
      days, ICU stay 1.8 versus 2.4 days, transfusion requirements 4.2 versus 5 units,
      early rebleeding 22%versus 30%, surgery 14%versus 12%, or late rebleeding
      16%versus 14% (mean follow-up of 62 and 58 months). CONCLUSION: Although urgent
      colonoscopy identified a definite source of LGIB more often than a standard care
      algorithm based on angiography and expectant colonoscopy, the approaches are not
      significantly different with regard to important outcomes. Thus, decisions
      concerning care for patients with acute LGIB should be based on individual
      experience and local expertise.

PMID- 16279892
TI  - Management of patients with severe hematochezia--with all current evidence
      available.
AB  - A randomized controlled trial (RCT) of routine urgent colonoscopy in severe lower
      gastrointestinal tract bleeding is reported in this journal from Duke. The only
      significant differences in results between the standard management (emergency red
      blood cell (RBC) scanning and angiography with elective colonoscopy) and urgent
      colonoscopy were in rates of finding a definitive bleeding site-one with a major
      stigmata of hemorrhage-and in not making a diagnosis. The trial was stopped early
      for logistics reasons a decade ago. The strengths and limitations of the study
      are discussed and contrasted with recent reports of other investigators. Similar
      to management of patients with non-variceal upper gastrointestinal tract (UGI)
      hemorrhage, triaging patients to level of care by comorbidity scores and stigmata
      of hemorrhage, successful colonoscopic hemostasis of focal lesions, and
      individualization of long-term medical, endoscopic, and surgical care are
      recommended based on promising reports by other investigators. Meanwhile, further
      RCTs for patients with severe hematochezia are warranted.

PMID- 16279893
TI  - A meta-analysis of the yield of capsule endoscopy compared to other diagnostic
      modalities in patients with obscure gastrointestinal bleeding.
AB  - OBJECTIVES: Due to its superior ability to examine the entire small bowel mucosa,
      capsule endoscopy (CE) has broadened the diagnostic evaluation of patients with
      obscure gastrointestinal bleeding (OGIB). Published studies have revealed a
      numerically superior performance of CE in determining a source of OGIB compared
      with other modalities, but due to small sample sizes, the overall magnitude of
      benefit is unknown. Additionally, the types of lesions more likely to be found by
      CE versus alternate modalities are also unknown. The aim of this study was to
      evaluate the yield of small bowel findings with CE in patients with OGIB compared
      to other modalities using meta-analysis. METHODS: We performed a recursive
      literature search of prospective studies comparing the yield of CE to other
      modalities in patients with OGIB. Data on yield and types of lesions identified
      among various modalities were extracted, pooled, and analyzed. Incremental yield
      (IY) (yield of CE-yield of comparative modality) and 95% confidence intervals
      (95% CI) of CE over comparative modalities were calculated. RESULTS: A total of
      14 studies (n = 396) compared the yield of CE with push enteroscopy for OGIB. The
      yield for CE and push enteroscopy was 63% and 28%, respectively (IY = 35%, p <
      0.00001, 95% CI = 26-43%) and for clinically significant findings (n = 376) was
      56% and 26%, respectively (IY = 30%, p < 0.00001, 95% CI = 21-38%). Three studies
      (n = 88) compared the yield of CE to small bowel barium radiography. The yield
      for CE and small bowel barium radiography for any finding was 67% and 8%,
      respectively (IY = 59%, p < 0.00001, 95% CI = 48-70%) and for clinically
      significant findings was 42% and 6%, respectively (IY = 36%, p < 0.00001, 95% CI
      = 25-48%). Number needed to test (NNT) to yield one additional clinically
      significant finding with CE over either modality was 3 (95% CI = 2-4). One study
      each compared the yield of significant findings on CE to intraoperative
      enteroscopy (n = 42, IY = 0%, p= 1.0, 95% CI =-16% to 16%), computed tomography
      enteroclysis (n = 8, IY = 38%, p= 0.08, 95% CI =-4% to 79%), mesenteric angiogram
      (n = 17, IY =-6%, p= 0.73, 95% CI =-39% to 28%), and small bowel magnetic
      resonance imaging (n = 14, IY = 36%, p= 0.007, 95% CI = 10-62%). Ten of the 14
      trials comparing CE with push enteroscopy classified the types of lesions found
      on examination. CE had a 36% yield for vascular lesions versus 20% for push
      enteroscopy, with an IY of 16% (p < 0.00001, 95% CI = 9-23%). Inflammatory
      lesions were also found more often in CE (11%) than in push enteroscopy (2%),
      with an IY of 9% (p= 0.0001, 95% CI = 5-13%). There was no significant difference
      in the yield of tumors or "other" findings between CE and push enteroscopy.
      CONCLUSIONS: CE is superior to push enteroscopy and small bowel barium
      radiography for diagnosing clinically significant small bowel pathology in
      patients with OGIB. In study populations, the IY of CE over push enteroscopy and
      small bowel barium radiography for clinically significant findings is >or=30%
      with an NNT of 3, primarily due to visualization of additional vascular and
      inflammatory lesions by CE.

PMID- 16279894
TI  - A prospective, randomized, double-blind, placebo-controlled trial of endoscopic
      steroid injection therapy for recalcitrant esophageal peptic strictures.
AB  - BACKGROUND AND AIMS: The aim of the study was to examine whether endoscopic
      intralesional corticosteroid injection into recalcitrant peptic esophageal
      strictures reduces the need for repeat stricture dilation. METHODS: Patients with
      a peptic esophageal stricture and recurrent dysphagia having had at least one
      dilation in the preceding 18 months were enrolled in a prospective randomized,
      double-blind study comparing steroid and sham injection. After endoscopic
      confirmation of recurrent stricture, patients were randomized to receive either
      0.5 cc/quadrant triamcinolone (40 mg/cc) or sham injection into the stricture
      followed by balloon dilation of the stricture. Patients were stratified by the
      number of dilations required in the preceding 18 months, severity of dysphagia,
      the presence of esophagitis, stricture severity, and prior therapy with a proton
      pump inhibitor. Patients and their physicians were blinded to the type of
      intervention received. Baseline dysphagia questionnaires were completed. Post
      procedurally all patients were placed on a standardized proton-pump inhibitor
      regimen and standardized telephone follow-up questionnaires were completed at 1
      wk and at 1, 3, 6, 9, and 12 months. The original sample-size calculation of 60
      patients could not be met in a timely fashion because of a low incidence of
      recalcitrant peptic stricture patients. RESULTS: A total of 30 patients were
      enrolled, 15 in the steroid group (10 men, mean age 66 yr) and 15 in the sham
      group (11 M, mean age 67 yr). Patients were followed for 1 yr, unless they
      underwent an antireflux operation or died. Two patients, one per group, died of
      non-esophageal causes at 1 and 12 months. Four patients had fundoplication, two
      in each group, unrelated to stricture or dysphagia. Two patients in the steroid
      group (13%) and nine in the sham group (60%) required repeat dilation (p= 0.011).
      CONCLUSIONS: In patients with recalcitrant peptic esophageal stricture, steroid
      injection into the stricture combined with acid suppression significantly
      diminishes both the need for repeat dilation and the average time to repeat
      dilation compared to sham injection and acid suppression alone.

PMID- 16279895
TI  - Palliation of nonresectable bile duct cancer: improved survival after
      photodynamic therapy.
AB  - OBJECTIVES: Preliminary uncontrolled studies of photodynamic therapy (PDT) of
      bile duct cancer (BDC) have shown astonishingly good results in the reduction of
      cholestasis, improvement of life quality, and potential improvement of survival
      time. Therefore, we investigated the influence of PDT on survival time in
      advanced BDC in a randomized controlled study. METHODS: Thirty-two patients with
      nonresectable BDC were randomized. In the PDT group 48 h after intravenous
      application of 2 mg/kg body weight of Photosan-3((R)), light activation was
      performed. In the control group, patients were treated with endoprostheses but no
      PDT. RESULTS: PDT group and the control group were comparable due to age, gender,
      performance status, bilirubin level, and BDC stage (Bismuth classification). The
      median survival time after randomization was 7 months for the control group and
      21 months for the PDT group (p= 0.0109). In half of the initially percutaneously
      treated patients, we could change from percutaneous to transpapillary drainage
      after PDT. Four patients showed infectious complications after PDT versus one
      patient in the control group. DISCUSSION: PDT is minimally invasive but shows a
      considerable postinterventional cholangitis rate. PDT has the potential to result
      in a changeover of current palliative treatment of BDC.

PMID- 16279896
TI  - The journal impact factor as a predictor of trial quality and outcomes: cohort
      study of hepatobiliary randomized clinical trials.
AB  - OBJECTIVES: To examine the association between the impact factor and
      characteristics of hepatobiliary randomized clinical trials. METHODS: A cohort
      study of 530 hepatobiliary randomized clinical trials was performed. The journal
      impact factor was extracted from Science Citation Index. For each trial, we
      extracted the sample size, the quality of randomization and blinding methods, and
      the statistical significance of the primary outcome measure. RESULTS: The median
      sample size was 45 participants (interquartile range 25-88). The allocation
      sequence generation was adequate in 273 trials (52%). Allocation concealment was
      adequate in 178 trials (34%). The primary outcome measure was statistically
      significant in 374 (71%) trials. Nonparametric analyses for trend indicated that
      the impact factor was significantly associated with the sample size (p < 0.01)
      and the proportion of trials with adequate allocation sequence generation (p <
      0.01) or allocation concealment (p= 0.02). The impact factor was not
      significantly associated with the study outcome (p= 0.28). CONCLUSIONS: The
      present study supports the use of the impact factor as a rough quality indicator.
      However, even trials in high impact journals may be small or may have inadequate
      quality. Critical appraisal of individual trials is always necessary,
      irrespective of the place of publication.

PMID- 16279897
TI  - The journal impact factor: judging a book by its cover.
AB  - Journal impact factors have been used to evaluate the quality of the work of an
      individual author and as a guide to the quality of a given study. Despite a rough
      correlation between the quality of an article and the impact factor of the
      journal it is published in, the reader cannot be sure of the value of an
      individual article without a careful appraisal of its content.

PMID- 16279898
TI  - Hypoadiponectinemia predicts the severity of hepatic fibrosis and pancreatic Beta
      cell dysfunction in nondiabetic nonobese patients with nonalcoholic
      steatohepatitis.
AB  - OBJECTIVES: The relationships between the adipokines tumor necrosis factor (TNF)
      alpha and adiponectin and the parameters of glucose homeostasis and severity of
      liver disease were assessed in nonobese nondiabetic subjects with nonalcoholic
      steatohepatitis (NASH). METHODS: A frequently sampled intravenous glucose
      tolerance test, serum cytokine measurement, and 7-day alimentary record were
      performed in 20 biopsy-proven NASH patients and 45 age-, sex-, and BMI-matched
      controls (30 insulin sensitive and 15 insulin resistant). RESULTS: Patients with
      NASH had impaired pancreatic beta-cell function compared with both insulin
      sensitive (adaptation index, AI: 97.7 +/- 17.7 vs 307.4 +/- 24.1 min(-2) mmol(-1)
      L; p= 0.00001) and insulin-resistant (adaptation index, AI: 97.7 +/- 17.7 vs
      201.4 +/- 41.1 min(-2) mmol(-1) L; p= 0.001) controls. Serum adiponectin levels
      were also significantly lower in the NASH group than in the two control groups
      and correlated with adaptation index and with the severity of hepatic steatosis,
      necroinflammation, and fibrosis. When NASH patients were grouped according to the
      severity of histological liver damage, adiponectin was the only variable
      discriminating patients with higher necroinflammatory grade and fibrosis score
      from those with milder lesions. CONCLUSIONS: Beta-cell secretory impairment is
      present in nonobese patients with NASH before glucose intolerance appears and may
      contribute to their increased risk for developing diabetes. Hypoadiponectinemia
      is a feature of NASH and may have a pathogenetic role in beta-cell dysfunction
      and in hepatic necroinflammation and fibrosis, independently of insulin
      resistance, visceral fat accumulation, TNF-alpha axis activity, and dietary
      habits. Our findings provide further rationale for therapeutic approaches aimed
      at increasing adiponectin levels together with restoring beta-cell function and
      insulin sensitivity.

PMID- 16279899
TI  - Response of hepatitis C genotype-4 naive patients to 24 weeks of Peg-interferon
      alpha2b/ribavirin or induction-dose interferon-alpha2b/ribavirin/amantadine: a
      non-randomized controlled study.
AB  - BACKGROUND AND AIM: Currently, pegylated interferon is the most effective therapy
      for hepatitis C but its cost is out of reach of most patients in the developing
      countries. The aim of this study was to assess the response rate of genotype-4
      patients to 24 wks of peg-interferon-alpha2b (Peg-IFN-alpha2b) and ribavirin
      (RBV) or interferon-alpha2b (IFN-alpha2b) with RBV and amantadine (AMD) as an
      alternative option. METHODS: In a controlled study, 180 biopsy-proven naive
      chronic hepatitis C patients were allocated into three groups based on their
      financial affordability to any of the study regimens. Group I (control) comprised
      40 patients who received Peg-IFN-alpha2b in a flat dose of 100 mug/wk (the dose
      available in Egypt) plus RBV 1,000-1,200 mg per day based on body weight for 48
      wks. Group II comprised 70 patients who received the same regimen for 24 wks.
      Group III comprised 70 patients who received induction-dose triple therapy (IDTT)
      in the form of IFN-alpha2b 3 MU once daily for the first 4 wks then reduced to
      TIW for 20 wks plus RBV 1,000-1,200 mg per day based on body weight and AMD 100
      mg twice daily for 24 wks. Six patients from group I, eight patients from group
      II, and four from group III discontinued the study either due to financial
      limitations and/or intolerable adverse effects of the drugs. RESULTS: Intention
      to-treat analysis revealed that sustained virological response (SVR) achieved in
      22 (55.0%), 34 (48.6%), and 20 (28.6%) in groups I, II, and III, respectively.
      Adherence-to-treatment analysis (80/80/80) revealed that SVR achieved in 22
      (64.7%), 34 (54.8%), and 20 (30.3%) in groups I, II, and III, respectively. In
      absence of eradication of hepatitis-C-virus-RNA at week 12, there was virtually
      no chance of achieving SVR. These data collectively may indicate that genotype 4
      is "not difficult to treat" as previously reported. CONCLUSION: Response of
      genotype-4 patients to 24 wks of Peg-IFN-alpha2b/RBV did not significantly differ
      from 48 wks, but was significantly higher than IDTT. Although SVR achieved by
      IDTT is less than Peg-IFN-alpha, yet it might provide a second option when the
      latter is not affordable. Early virological response should be used as a
      predictor to SVR to avoid unnecessary expenses in nonresponders patients.

PMID- 16279900
TI  - A randomized trial of pegylated interferon alpha-2b plus ribavirin in the
      retreatment of chronic hepatitis C.
AB  - OBJECTIVES: The efficacy of combination therapy with pegylated interferon (PEG
      IFN) alpha plus ribavirin (RBV) in the retreatment of chronic hepatitis C (CHC)
      in patients who previously failed combination standard IFN plus RBV or IFN
      monotherapy has not been well established. METHODS: Three hundred and twenty-one
      CHC patients including virologic nonresponders to combination IFN plus RBV (n =
      219) or IFN monotherapy (n = 47), and relapsers to combination therapy (n = 55)
      were randomized to receive PEG IFN alpha-2b 1.5 microg/kg per wk plus RBV 800 mg
      per day (Regimen A, n = 160) or PEG IFN alpha-2b 1.0 microg/kg per wk plus RBV
      1,000-1,200 mg per day (Regimen B, n = 161) for 48 wks. RESULTS: Sustained
      virologic response (SVR) occurred in 16% of the overall study population (Regimen
      A vs B, 18%vs 13%, p= 0.21), in 8% of the combination therapy nonresponders
      (10%vs 6%, p= 0.35), in 21% of the IFN monotherapy nonresponders (16%vs 27%, p=
      0.35), and in 42% of the combination therapy relapsers (50%vs 32%, p= 0.18). In
      nonresponders to prior combination therapy, HCV ribonucleic acid levels <100,000
      copies/mL at the end of the prior treatment course were associated with an
      increased SVR compared with levels >or=100,000 copies/mL (21%vs 5%, p= 0.002). In
      the overall study population, genotype 1 patients had lower SVR rates than others
      (14%vs 33%, p= 0.01), and African Americans had lower SVR than Caucasians (4%vs
      18%, p= 0.01). CONCLUSION: Combination therapy with PEG IFN alpha-2b plus RBV is
      more effective in patients who relapsed after combination standard IFN plus RBV
      than in nonresponders to either combination therapy or IFN monotherapy. There was
      no significant effect of dosing regimen.

PMID- 16279901
TI  - Higher efficacy of sequential therapy with interferon-alpha and lamivudine
      combination compared to lamivudine monotherapy in HBeAg positive chronic
      hepatitis B patients.
AB  - BACKGROUND: Monotherapy with interferon (IFN) or lamivudine is effective in a
      limited proportion of chronic hepatitis B (CHB) patients. A sequential
      combination may have better therapeutic effects by sustained viral suppression
      combined with immunomodulation. AIM: To compare the efficacy of sequential
      lamivudine and IFN therapy versus lamivudine monotherapy in HBeAg positive CHB
      patients. PATIENTS AND METHODS: Seventy-five treatment naive HBeAg positive
      patients with histologically proven CHB and alanine aminotransferase (ALT) >1.5 x
      ULN received lamivudine 100 mg per day for 52 wks with IFN 5 MIU per day added
      for 16 wks after the first 8 wks (group A, n = 38; age 30 +/- 12 yr; M:F = 35:3)
      or lamivudine 100 mg per day for 52 wks (group B, n = 37; age 30 +/- 16 yr; M:F =
      31:6). Biochemical and virologic responses were assessed at weeks 52 and 76 and
      analysis was done on intention-to-treat. Serial samples were studied for the
      emergence of lamivudine-resistant YM552I/VDD mutations by direct sequencing.
      RESULTS: At week 52, HBeAg loss occurred in 15 (39.5%) in group A and 14 (37.8%)
      in group B (p= 1.00). HBeAg loss, anti-HBe appearance, and undetectable DNA
      levels were seen in 26.3% and 13.5% (p= 0.249), respectively. Nine of 10 (90%)
      patients in group A and 1 of 5 (20%) in group B maintained the response through
      week 76 (p= 0.017). At week 76, 5 additional patients in group A and 3 in group B
      further achieved the primary end point and the overall HBeAg loss was observed in
      44.7% and 18.9% (p= 0.025) and HBeAg loss, anti-HBe appearance, and undetectable
      hepatitis B virus (HBV) DNA levels in 36.8% and 10.8% in group A and group B,
      respectively (p= 0.026). At week 76, undetectable HBV DNA was seen in 39.5% and
      16.2% in groups A and B, respectively (p= 0.039). Normal ALT was seen in 47.7%
      and 40.5% at week 52 (p= 0.489) and ALT was normal in 39.5% and 13.5% at week 76
      (p= 0.018) in groups A and B, respectively. YM552I/VDD-resistant mutants emerged
      in 6 of 38 (15.5%) patients in group A, and 3 of 37 (8.1%) in group B (p= ns).
      The rate of histological improvement was comparable in the two groups.
      CONCLUSIONS: Our results demonstrate that sequential therapy is superior to
      lamivudine monotherapy in achieving sustained seroconversion, ALT normalization,
      and HBV DNA loss. Compared to 80% with sequential therapy, only 20% Indian
      patients with CHB did not relapse after stopping lamivudine monotherapy.

PMID- 16279903
TI  - Delayed-release oral mesalamine at 4.8 g/day (800 mg tablet) for the treatment of
      moderately active ulcerative colitis: the ASCEND II trial.
AB  - BACKGROUND AND AIMS: Preliminary data have shown that delayed release oral
      mesalamine (Asacol) dosed at 4.8 g/day provided additional efficacy benefit
      compared to 1.6 g/day in patients with mildly to moderately active ulcerative
      colitis. Additionally, Asacol dosed at 2.4 g/day has been proved to be more
      effective than 1.6 g/day. Whether 4.8 g/day of mesalamine (dosed with an
      investigational 800 mg tablet) is more effective than Asacol 2.4 g/day (dosed
      with a 400 mg tablet) in patients with moderately active ulcerative colitis is
      unknown. METHODS: A randomized, double-blind, controlled trial (ASCEND II) was
      conducted to evaluate the efficacy of 4.8 g/day of mesalamine in adults with
      active ulcerative colitis. Three hundred eighty-six patients with mild to
      moderate ulcerative colitis were randomized for treatment with mesalamine 2.4
      g/day (400 mg tablet) or 4.8 g/day (800 mg tablet) for 6 wk. The primary efficacy
      population was 268 patients with moderately active ulcerative colitis treated
      with 2.4 g/day (n = 139) or 4.8 g/day (n = 129). The primary endpoint was the
      proportion of patients in each treatment group that achieved overall improvement
      ("treatment success," defined as either complete remission or a clinical response
      to therapy) from baseline at week 6. RESULTS: Seventy-two percent of patients
      receiving 4.8 g/day of mesalamine for moderate ulcerative colitis (89/124
      patients) achieved treatment success at week 6, compared with 59% of those who
      received 2.4 g/day (77/130 patients) (p= 0.036). Both regimens were well
      tolerated. Adverse events and clinically significant changes in laboratory
      results were similar in both treatment groups. CONCLUSIONS: Patients with
      moderately active ulcerative colitis treated with 4.8 g/day of mesalamine (800 mg
      tablet) are significantly more likely to achieve overall improvement at 6 wk
      compared to patients treated with 2.4 g/day.

PMID- 16279902
TI  - Anti-tissue transglutaminase antibodies in patients with abnormal liver tests: is
      it always coeliac disease?
AB  - BACKGROUND: Coeliac disease (CD) is found in 5-10% of patients with chronically
      abnormal liver tests and no obvious cause of liver disease. In this population
      the efficacy of screening for CD by anti-tissue transglutaminase (anti-tTG) may
      be impaired by the high rate of positive anti-tTG found in chronic liver disease.
      AIMS: To evaluate the prevalence of coeliac disease and the role of anti-tTG in
      patients with non-viral, non-autoimmune chronic and no obvious cause of liver
      damage. METHODS: Out of 2,512 consecutive patients with abnormal liver tests, 168
      (118 men, 50 women; mean age 40.7 +/- 12.6 years) were defined, on the basis of
      clinical data and liver biopsy, as NAFLD or cryptogenic chronic hepatitis. All
      were tested by recombinant IgA and IgG anti-tissue transglutaminase. Patients
      with a positive serology underwent endoscopy with duodenal biopsies. RESULTS:
      NAFLD was diagnosed in 121 patients, in 6 associated with cirrhosis, while 47
      patients were considered as cryptogenic hepatitis in the absence of steatosis.
      Anti-tTG were positive in 20/168 patients (3 IgA alone; 11 IgG alone; 6 both IgA
      and IgG). Coeliac disease was found at endoscopy and confirmed by histopathology
      only in the 6 patients (3.6%) with both IgA and IgG anti-tTG positivity. Four of
      the patients with CD had NAFLD (3.3%), in 2 of them associated with cirrhosis;
      while 2 of those with cryptogenic hepatitis (4.2%) had CD. CONCLUSIONS: The
      prevalence of CD in patients with chronically abnormal liver tests of unexplained
      etiology is 4%, with no relation with the degree of liver steatosis. Screening
      should be done by testing for IgA and IgG antibodies and then evaluating by
      endoscopy and biopsy only patients positive for both.

PMID- 16279904
TI  - Disease concordance, zygosity, and NOD2/CARD15 status: follow-up of a population
      based cohort of Danish twins with inflammatory bowel disease.
AB  - OBJECTIVES: A Danish cohort of twins with inflammatory bowel disease (IBD),
      Crohn's disease (CD) and ulcerative colitis (UC), has previously been collected.
      The aim of the present study was to reassess this cohort in order to compare
      clinical characteristics in concordant versus discordant twin pairs, test twin
      zygosity genetically, follow-up on disease concordance, and examine NOD2/CARD15
      genetic status. METHODS: The Danish cohort is one of two population-based cohorts
      worldwide and consists of 103 twin pairs. After median 13 yr of follow-up, all
      twins were contacted and hospital files were scrutinized to reassess disease
      concordance and obtain phenotype data. DNA was obtained from 123 twins for
      analysis of zygosity and prevalence of the three common NOD2/CARD15 mutations.
      RESULTS: Zygosity tested genetically was consistent with the former assessment
      based on questionnaires. The proband concordance for CD remained fairly stable:
      63.6% among monozygotic (MZ) twins and 3.6% among dizygotic (DZ) twins. Clinical
      characteristics were similar in twins from concordant versus discordant pairs.
      Forty-four percent of patients with CD were positive for >or=1 mutant allele of
      NOD2/CARD15 compared to 2% of UC patients (p < 0.001) and 19% of healthy twins
      (p= 0.02). The allele mutation frequency was 43% among the healthy twins to
      patients with CD versus 9% among twins to UC patients (p= 0.01). CONCLUSIONS:
      Previous questionnaire assessment of twin zygosity was confirmed by genetic test.
      Concordance for CD remained quite stable and was significantly higher among MZ
      than DZ twins. A high NOD2/CARD15 mutation frequency was observed both among CD
      twins and their healthy siblings.

PMID- 16279906
TI  - Intravenous iron sucrose versus oral iron supplementation for the treatment of
      iron deficiency anemia in patients with inflammatory bowel disease--a randomized,
      controlled, open-label, multicenter study.
AB  - OBJECTIVES: Anemia is a frequent complication in patients with inflammatory bowel
      disease (IBD). The optimal route for iron supplementation to replenish iron
      stores has not been determined so far. We therefore evaluated the efficacy and
      safety of intravenous iron sucrose as compared with oral iron sulfate for the
      treatment of iron deficiency anemia (IDA) in patients with IBD. METHODS: A
      randomized, prospective, open-label, multicenter study was performed in 46
      patients with anemia and transferrin saturation <or=20% and/or serum ferritin
      concentrations <or=20 microg/L. The intravenous group received a single dose of
      iron sucrose of 7 mg iron/kg body weight, followed by five 200 mg infusions for
      the following 5 wks. The oral group received iron sulfate 100-200 mg per day for
      6 wks. RESULTS: While a comparable increase in hemoglobin was observed for both
      administration routes (median increase 0.25 g/L in the intravenous group vs 0.21
      g/L in the oral group), only iron sucrose led to a rise in serum ferritin
      concentrations. Intractable gastrointestinal adverse events caused permanent
      study drug discontinuation in five patients (20.8%) receiving iron sulfate,
      whereas only one patient (4.5%) had to be withdrawn because of side effects due
      to iron sucrose. CONCLUSIONS: Although being equal in short-term efficacy and
      overall tolerability our results suggest a better gastrointestinal tolerability
      for iron sucrose. Larger trials are mandatory to prove a possible advantage of
      iron sucrose in short- and long-term efficacy as well as in tolerability over
      iron sulfate in the management of IDA in IBD.

PMID- 16279905
TI  - A prospective comparison study of MRI versus small bowel follow-through in
      recurrent Crohn's disease.
AB  - BACKGROUND: We aimed to determine the utility of magnetic resonance imaging (MRI)
      compared with small bowel follow-through (SBFT) in the assessment of known
      Crohn's disease. METHODS: Subjects, over age 18 yr who were to undergo SBFT
      investigations to assess for complications or extent of Crohn's disease were
      eligible. SBFT was performed by a single radiologist (IB), and within 4 wk MRI
      was performed by a single radiologist (HG) who was blinded to the SBFT results.
      For MRI, oral contrast was 2% barium sulfate (1,350 mL). After unenhanced T1
      weighted images and single shot fast spin echo T2 imaging, intravenous (IV)
      glucagon and gadolinium were given. Fast multiplanar spoiled-gradient recalled T1
      coronal sequences were obtained followed by abdominal and pelvic axial images.
      MRI and SBFT were compared for extent of disease, presence of complications, and
      for identification of extraintestinal disease. RESULTS: Paired studies were
      undertaken within a mean of 22 days in 30 subjects. Ten studies were normal by
      both modalities and 8 studies showed similar extent of Crohn's disease. SBFT
      revealed additional information in 4, including a stricture in 1 and ileosigmoid
      fistulas in 2. MRI provided enhanced information in 8, including identifying
      active inflammation in strictured areas based on wall enhancement patterns, vasa
      recta changes, and lymphadenopathy. CONCLUSIONS: On the basis of cost and
      accessibility, SBFT may still be a first line procedure of choice in some centers
      without MRI, but MRI's advantages of no radiation and the potential to identify
      active inflammation in strictured areas, extraintestinal, and colorectal disease
      make it an attractive alternative.

PMID- 16279907
TI  - Role of tumor necrosis factor-alpha and interleukin-10 gene polymorphisms in
      irritable bowel syndrome.
AB  - OBJECTIVES: Imbalances in the genetically controlled pro- and anti-inflammatory
      cytokine production may promote ongoing low-grade inflammation after an acute
      gastroenteritis, and subsequently, irritable bowel syndrome (IBS) (post
      infectious IBS, PI-IBS). We studied gene promoter single nucleotide polymorphisms
      (SNPs) of tumor necrosis factor-alpha (TNF-alpha, pro-inflammatory) and
      interleukin-10 (IL-10, anti-inflammatory) in IBS patients and controls. METHODS:
      DNA was extracted from peripheral blood leucocytes of 111 IBS patients and 162
      healthy controls. Genotype and allele frequencies were assessed by analyzing SNPs
      at position -308 (TNF-alpha) and -1082 and -819 (IL-10). RESULTS: Homozygous high
      producers for TNF-alpha (A/A) were rare (overall prevalence 2.6%). The
      heterozygous TNF-alpha genotype (G/A, high producer) was significantly more
      prevalent in IBS compared to controls (41%vs 26%, p= 0.02). More patients (41%)
      than controls (30%) were positive for the A allele (p= 0.044; odds ratio (OR)
      1.68, 95% confidence interval (CI) 1.01-2.79), with a similar trend for diarrhea
      (54%) versus constipation and alternating subtypes (<33%, p= 0.079), but not for
      subgroups according to a history of acute gastroenteritis. IL-10 genotypes were
      similarly distributed in patients and controls for both SNPs. Possession of a
      high producer TNF-alpha and a low producer IL-10 genotype were significantly more
      prevalent in IBS (9%) versus controls (3%, p= 0.035; OR 3.11, 95% CI 1.03-9.36)
      and in diarrhea (20%) compared to other IBS subtypes (<4%, p= 0.026).
      CONCLUSIONS: Our results support the emerging hypothesis that genetically
      determined immune activity plays a role in the pathophysiology of IBS. Future
      studies in larger, clinically relevant, IBS subgroups are warranted to establish
      definite associations with cytokine gene polymorphisms.

PMID- 16279908
TI  - Dysregulation of peripheral cytokine production in irritable bowel syndrome.

PMID- 16279909
TI  - Performance characteristics and evaluation of an automated-developed and
      quantitative, immunochemical, fecal occult blood screening test.
AB  - OBJECTIVES: Guaiac fecal occult blood colorectal cancer (CRC) screening tests
      (FOBT) are faulted for low sensitivity and nonspecificity for human hemoglobin
      (Hb). Automated-developed, immunochemical, human Hb FOBT (I-FOBT) is specific,
      eliminates diet restrictions, and Hb quantification allows selection of a
      threshold for colonoscopy. Aims were to determine 1) test reproducibility; 2)
      test stability; 3) intrapatient daily I-FOBT variation; 4) test sensitivity and
      specificity for neoplasia in 500 symptomatic/high-risk patients undergoing
      colonoscopy; and 5) to correlate fecal Hb measurements with findings. METHODS:
      The desktop instrument OC-Sensor (Eiken, Japan) automatically develops and
      quantitates 50 tests/h for Hb. Patients prepared three tests, which were
      quantified and then 1) repeatedly re-examined; 2) stored at 4 degrees C or 20
      degrees C or 28 degrees C and repeatedly examined; and 3) fecal Hb levels were
      correlated with colonoscopic findings. RESULTS: Five I-FOBTs re-examined five
      times in 1 day had no significant measurement changes. Thirty tests stored for 21
      or more days had a decay/day of 0.3%+/- 0.4 at 4 degrees C (NS), 2.2%+/- 1.7 at
      20 degrees C (NS), and 3.7%+/- 1.8 at 28 degrees C (p < 0.05). There were
      intrapatient variations between the three daily I-FOBTs (NS). At the recommended
      100 ng Hb/mL threshold, all six cases of CRCs and 20 out of 28 cases of advanced
      adenomas were detected; evaluated together their sensitivity and specificity were
      76.5% and 95.3%. CONCLUSIONS: Desktop, automated-developed, quantitative I-FOBT
      is now available. Refrigerated OC-Sensor samples are stable for 21 days, easy to
      prepare and develop and, at the 100 ng Hb/mL threshold, have high sensitivity,
      specificity, and negative predictive values for significant neoplasia.
      Suitability for population CRC screening awaits further evaluation.

PMID- 16279910
TI  - Inappropriate colorectal cancer screening: findings and implications.
AB  - OBJECTIVES: Inclusion of colorectal cancer screening as a performance measure in
      the Veterans Health Administration (VHA) health system appears to have improved
      screening rates but may have also increased inappropriate screening. Our aim was
      to ascertain whether the fecal occult blood test (FOBT) was being ordered
      appropriately. METHODS: We examined records of 500 consecutive primary care
      patients at a single VHA facility for whom FOBT had been ordered to determine
      whether the FOBT was appropriate and, if not, the reason why. RESULTS: We found
      that 18% of the sample had severe comorbid illness, 13% had signs or symptoms of
      gastrointestinal blood loss, 7% had a history of colorectal neoplasia or
      inflammatory bowel disease (high risk), 5% had undergone colonoscopy within prior
      5 yr, and 3% were younger than 50 yr of age. Overall, 35% of the patients had at
      least one reason that the FOBT was inappropriate and at least 19% of the patients
      should not have undergone any colorectal cancer test for screening or diagnosis.
      CONCLUSIONS: The FOBT order was inappropriate in a third of the sample, most
      commonly because of a documented life-limiting comorbidity. In addition, data
      suggested that FOBT was being used for diagnosis instead of screening. Screening
      patients unlikely to live long enough to develop and die from colorectal cancer
      provides no benefit and places these individuals at unjustifiable risk.
      Additionally, inappropriate screening utilizes resources that could be used to
      improve screening and follow-up for eligible individuals.

PMID- 16279911
TI  - Association between colonic screening, subject characteristics, and stage of
      colorectal cancer.
AB  - OBJECTIVES: Colorectal cancer remains a significant cause of mortality and
      morbidity in North America. Colorectal cancer survival is highly dependent on
      stage at diagnosis, therefore it is important to identify factors related to
      stage. This study evaluated the association between subject factors (e.g.,
      colonic screening, family history) and stage of colorectal cancer at diagnosis.
      METHODS: Population-based colorectal cancer cases recruited by the Ontario
      Familial Colon Cancer Registry between 1997 and 1999 were staged according to the
      tumor-nodal-metastasis (TNM) staging system and classified as early (TNM I/II) or
      late (TNM III/IV) stage. Epidemiologic information and stage was available for
      768 cases. Multivariate logistic regression was used to obtain odds ratios (OR)
      estimates. RESULTS: Having had screening endoscopy reduced the risk of late stage
      diagnosis (OR = 0.46, 95% CI 0.22-0.98). Being older (>45 yr) was associated with
      a reduced risk of late stage cancer (OR = 0.36, 95% CI 0.18-0.74), as was having
      a first degree relative with colorectal cancer (OR =0.66, 95% CI 0.46-0.95).
      Rural residence (OR = 1.48, 95% CI 1.01-2.17) and non-white ethnicity (OR = 3.34,
      95% CI 1.20-9.36) were associated with an increased risk of late stage cancer.
      CONCLUSIONS: Several factors are independently associated with late stage
      colorectal cancer. Colorectal cancer screening awareness and education programs
      need to consider targeting persons most likely to present with late stage
      colorectal cancer.

PMID- 16279912
TI  - Small gallstones are associated with increased risk of acute pancreatitis:
      potential benefits of prophylactic cholecystectomy?
AB  - OBJECTIVES: Pancreatitis is a severe complication of gallstone disease with
      considerable mortality. Small gallstones may increase the risk of pancreatitis.
      Our aims were to evaluate potential association of small stones with pancreatitis
      and potential beneficial effects of prophylactic cholecystectomy. METHODS: Stone
      characteristics were determined in patients with biliary pancreatitis (115),
      obstructive jaundice due to gallstones (103), acute cholecystitis (79), or
      uncomplicated gallstone disease (231). Sizes and numbers of gallbladder and bile
      duct stones were determined by ultrasonography and endoscopic retrograde
      cholangiopancreatography, respectively. Effects of prophylactic cholecystectomy
      were assessed by decision analyses with a Markov model and Monte Carlo
      simulations. RESULTS: Patients with pancreatitis or obstructive jaundice had more
      and smaller gallbladder stones than those with acute cholecystitis or
      uncomplicated disease (diameters of smallest stones: 3 +/- 1, 4 +/- 1, 8 +/- 1,
      and 9 +/- 1 mm, respectively, p < 0.01). Bile duct stones were smaller in case of
      pancreatitis than in obstructive jaundice (diameters of smallest stones: 4 +/- 1
      vs 8 +/- 1, p < 0.01). Multivariate analysis identified old age and small stones
      as independent risk factors for pancreatitis. Decision analysis in a
      representative group of patients with small (<or=5 mm) gallstones (5,000
      patients, 67% females, 45 yr old, 10-yr follow-up) indicates that life-years may
      be gained or lost by cholecystectomy, depending on incidence and mortality of
      pancreatitis. CONCLUSIONS: Small gallstones are associated with pancreatitis.
      Prophylactic cholecystectomy may lead to gain or loss of life-years in patients
      with small stones, depending on incidence and mortality of pancreatitis.

PMID- 16279913
TI  - Expression of Fas ligand by hepatic macrophages in patients with fulminant
      hepatic failure.
AB  - OBJECTIVES: The mechanisms of Fas-Fas ligand (Fas-FasL)-mediated apoptosis in the
      pathogenesis of fulminant hepatic failure (FHF) have not been well defined. This
      clinical study was carried out to assess which cells expressed Fas-FasL and to
      determine their involvement. METHODS: The subjects were 24 patients with FHF who
      underwent liver transplantation at our institution. For comparison, nine chronic
      hepatitis (CH) patients and six living liver donors (LD) were also enrolled.
      Liver tissues were obtained for histological (hematoxylin-eosin, terminal
      deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick-end labeling
      [TUNEL], immunohistochemistry, and double immunofluorescence staining) and
      reverse transcription PCR (RT-PCR; cytokines and chemokines) analysis. RESULTS:
      The numbers of TUNEL-, FasL-, and CD68-positive cells in the livers of patients
      with FHF were significantly larger than in those with CH or with normal livers.
      Double immunofluorescence staining showed that FasL was expressed predominantly
      on liver macrophages and rarely on CD8-positive lymphocytes. RT-PCR study showed
      increased expression of FasL; interferon-gamma; interleukin-18; macrophage
      inhibitory protein-1beta; and regulated upon activation, normal T cell expressed
      and secreted in the livers of patients with FHF compared with those of LD.
      CONCLUSIONS: Macrophages and their expression of FasL may play roles in the
      pathogenesis of FHF.

PMID- 16279915
TI  - New advances in evaluation and management of patients with polycystic liver
      disease.
AB  - Adult polycystic liver disease (APLD) is an autosomal dominant condition most
      commonly associated with polycystic kidney disease. However, over the last decade
      it has come to be recognized that APLD is a genetically heterogeneous disorder
      involving derangements on at least three different chromosomes. Mutations
      involving chromosomes 16 and 4 accounting for autosomal dominant polycystic
      kidney disease (ADPKD) type 1 and type 2 have been well described as have their
      gene products, polycystin-1 and polycystin-2. These have since been joined by a
      more recently recognized mutation in the short arm of chromosome 19 thought to be
      responsible for a much rarer form of autosomal dominant polycystic liver disease
      without any associated renal involvement. Despite the sometimes impressive
      physical and radiologic findings, only a minority of patients will progress to
      advanced liver disease or develop complications as a result of massive
      hepatomegaly. In these patients, medical management alone has proved ineffectual.
      Therefore, in the symptomatic APLD patient, surgical therapy remains the mainstay
      of therapy and includes cyst aspiration and sclerosis, fenestration with and
      without hepatic resection and orthotopic liver transplantation. The surgical
      literature on treatment of APLD, to include outcome measurements and complication
      rates are summarized. Additionally, we review other potential organ involvement
      and resultant complications.

PMID- 16279914
TI  - Interactions between commensal bacteria and gut sensorimotor function in health
      and disease.
AB  - Commensal bacteria inhabiting the human intestine (i.e., intestinal microflora)
      participate in the development and maintenance of gut sensory and motor
      functions, including the promotion of intestinal propulsive activity. On the
      other hand, intestinal motility represents one of the major control systems of
      gut microflora, through the sweeping of excessive bacteria from the lumen. There
      is emerging evidence indicating that changes in this bidirectional interplay
      contribute to the pathogenesis of gut diseases, such as small intestinal
      bacterial overgrowth and intestinal pseudo-obstruction. Recent interest has also
      been directed to the potential role of intestinal microflora in the pathogenesis
      of the irritable bowel syndrome. Although the status of intestinal microflora in
      the irritable bowel syndrome remains unsettled, small intestinal bacterial
      overgrowth (as detected with breath testing) and increased fermentation of foods
      with gas production, provide indirect evidence that microflora may contribute to
      symptom generation in irritable bowel syndrome. The potential benefit of
      antibiotic and probiotic therapy is currently under investigation and opens new
      perspectives in irritable bowel syndrome treatment.

PMID- 16279916
TI  - Milk thistle for alcoholic and/or hepatitis B or C liver diseases--a systematic
      cochrane hepato-biliary group review with meta-analyses of randomized clinical
      trials.
AB  - OBJECTIVES: Our objectives were to assess the beneficial and harmful effects of
      milk thistle (MT) or MT constituents versus placebo or no intervention in
      patients with alcoholic liver disease and/or hepatitis B and/or C liver diseases.
      METHODS: Randomized clinical trials studying patients with alcoholic and/or
      hepatitis B or C liver diseases were included (December 2003). The randomized
      clinical trials were evaluated by components of methodological quality. RESULTS:
      Thirteen randomized clinical trials assessed MT in 915 patients with alcoholic
      and/or hepatitis B or C liver diseases. The methodological quality was low: only
      23% of the trials reported adequate allocation concealment and only 46% were
      considered double blind. MT versus placebo or no intervention for a median
      duration of 6 months had no significant effects on all-cause mortality (relative
      risk (RR) 0.78, 95% confidence interval (CI) 0.53-1.15), complications of liver
      disease, or liver histology. Liver-related mortality was significantly reduced by
      MT in all trials (RR 0.50, 95% CI 0.29-0.88), but not in high-quality trials (RR
      0.57, 95% CI 0.28-1.19). MT was not associated with a significantly increased
      risk of adverse events. CONCLUSIONS: Based on high-quality trials, MT does not
      seem to significantly influence the course of patients with alcoholic and/or
      hepatitis B or C liver diseases. MT could potentially affect liver injury.
      Adequately conducted randomized clinical trials on MT versus placebo may be
      needed.

PMID- 16279917
TI  - Hemobilia caused by cytomegalovirus cholangiopathy.
AB  - A 57-yr-old male on long-term steroid therapy presented with hematemesis, fever,
      and a retroperitoneal fluid collection. Hemobilia was diagnosed, but the cause
      was not identified by ERCP, computed tomography, or angiography. Peroral
      cholangioscopy revealed multiple biliary ulcers. Cholangioscopic biopsies
      diagnosed cytomegalovirus (CMV) infection. Intravenous ganciclovir therapy was
      initiated, and was associated with cessation of bleeding. Biliary CMV disease is
      rare in HIV-negative persons, but should be considered in a patient with
      unexplained hemobilia. Cholangioscopy may be useful for diagnosis.

PMID- 16279919
TI  - Pyogenic liver abscess and occult colon cancer.

PMID- 16279921
TI  - Three-dimensional linear endoscopic ultrasound.

PMID- 16279922
TI  - New criteria for irritable bowel syndrome based on prospective symptom
      evaluation.

PMID- 16279924
TI  - Obesity and GERD: implications and consequences for bariatric surgery?

PMID- 16279923
TI  - Age and sex distribution of the incidence of Barrett's esophagus found in a Dutch
      primary care population.

PMID- 16279925
TI  - Genesis of a curmudgeon.

PMID- 16279927
TI  - Serum oligoclonal immunoglobulin bands in cirrhotic patients.

PMID- 16279926
TI  - A116C angiotensin II type 1 receptor gene polymorphism may predict hemodynamic
      response to losartan in patients with cirrhosis and portal hypertension.

PMID- 16279928
TI  - Colonic ulceration after sodium phosphate bowel preparation.

PMID- 16279929
TI  - Promotion of proximal reflux in adults and infants.

PMID- 16279932
TI  - Orphan GPCRs in the regulation of sleep and circadian rhythm.

PMID- 16279933
TI  - The hypocretins and sleep.
AB  - The hypocretins (also called the orexins) are two neuropeptides derived from the
      same precursor whose expression is restricted to a few thousand neurons of the
      lateral hypothalamus. Two G-protein coupled receptors for the hypocretins have
      been identified, and these show different distributions within the central
      nervous system and differential affinities for the two hypocretins. Hypocretin
      fibers project throughout the brain, including several areas implicated in
      regulation of the sleep/wakefulness cycle. Central administration of synthetic
      hypocretin-1 affects blood pressure, hormone secretion and locomotor activity,
      and increases wakefulness while suppressing rapid eye movement sleep. Most human
      patients with narcolepsy have greatly reduced levels of hypocretin peptides in
      their cerebral spinal fluid and no or barely detectable hypocretin-containing
      neurons in their hypothalamus. Multiple lines of evidence suggest that the
      hypocretinergic system integrates homeostatic, metabolic and limbic information
      and provides a coherent output that results in stability of the states of
      vigilance.

PMID- 16279934
TI  - Neuropeptide S as a novel arousal promoting peptide transmitter.
AB  - Behavioral arousal requires integration of multiple neurotransmitter and
      neuromodulatory systems. Identifying these systems is the key to not only a
      better understanding of the neurobiology of sleep/wakefulness but may also lead
      to the discovery of potential therapeutic targets for various sleep disorders. We
      review here a novel arousal promoting neuropeptide system, neuropeptide S (NPS)
      and its receptor. Pharmacologically, NPS activates NPS receptors at low nanomolar
      concentration to increase concentrations of intracellular Ca(2+). Anatomically,
      both NPS precursor and receptor mRNAs are found predominately in the central
      nervous system. NPS precursor mRNA is expressed only in several discrete regions
      located mainly in the brainstem. In particular, it is highly expressed in a
      previously undescribed group of neurons localized between locus coeruleus and
      Barrington's nucleus. NPS receptor mRNA is widely distributed in many brain areas
      with high expression levels in cortex, hypothalamus, amygdala and multiple
      midline thalamic nuclei. Functionally, central administration of NPS increases
      locomotor activity in both naive and habituated mice. It also significantly
      increases wakefulness and decreases paradoxical (rapid eye movement) sleep and
      slow wave sleep in rats. In addition, NPS suppresses anxiety-like behaviors in
      mice exposed to different behavioral paradigms measuring responses to novelty or
      stress. These studies indicate that the NPS system is a newly discovered
      transmitter system that regulates vigilance and emotional states. NPS appears to
      possess a unique pharmacological profile in producing both anxiolytic-like and
      hypervigilant effects.

PMID- 16279935
TI  - From heart to mind. The urotensin II system and its evolving neurophysiological
      role.
AB  - The discovery of novel biologically active peptides has led to an explosion in
      our understanding of the molecular mechanisms that underlie the regulation of
      sleep and wakefulness. Urotensin II (UII), a peptide originally isolated from
      fish and known for its strong cardiovascular effects in mammals, is another
      surprising candidate in the regulatory network of sleep. The UII receptor was
      found to be expressed by cholinergic neurons of laterodorsal and pedunculopontine
      tegmental nuclei, an area known to be of utmost importance for the on- and offset
      of rapid eye movement (REM) sleep. Recently, physiological data have provided
      further evidence that UII is indeed a modulator of REM sleep. The peptide
      directly excites cholinergic mesopontine neurons and increases the rate of REM
      sleep episodes. These new results and its emerging behavioral effects establish
      UII as a neurotransmitter/neuromodulator in mammals and should spark further
      interest into the neurobiological role of the peptide.

PMID- 16279937
TI  - Evolutionary mechanisms acting on proteinase inhibitor variability.
AB  - The interaction of proteinase inhibitors produced, in most cases, by host
      organisms and the invasive proteinases of pathogens or parasites or the dietary
      proteinases of predators, results in an evolutionary 'arms race' of rapid and
      ongoing change in both interacting proteins. The importance of these interactions
      in pathogenicity and predation is indicated by the high level and diversity of
      observable evolutionary activity that has been found. At the initial level of
      evolutionary change, recruitment of other functional protein-folding families has
      occurred, with the more recent evolution of one class of proteinase inhibitor
      from another, using the same mechanism and proteinase contact residues. The
      combination of different inhibitor domains into a single molecule is also
      observed. The basis from which variation is possible is shown by the high rate of
      retention of gene duplication events and by the associated process of inhibitory
      domain multiplication. At this level of reorganization, mutually exclusive
      splicing is also observed. Finally, the major mechanism by which variation is
      achieved rapidly is hypervariation of contact residues, an almost ubiquitous
      feature of proteinase inhibitors. The diversity of evolutionary mechanisms in a
      single class of proteins is unlikely to be common, because few systems are under
      similar pressure to create variation. Proteinase inhibitors are therefore a
      potential model system in which to study basic evolutionary process such as
      functional diversification.

PMID- 16279938
TI  - Structural and functional specificities of PDGF-C and PDGF-D, the novel members
      of the platelet-derived growth factors family.
AB  - The platelet-derived growth factor (PDGF) family was for more than 25 years
      assumed to consist of only PDGF-A and -B. The discovery of the novel family
      members PDGF-C and PDGF-D triggered a search for novel activities and
      complementary fine tuning between the members of this family of growth factors.
      Since the expansion of the PDGF family, more than 60 publications on the novel
      PDGF-C and PDGF-D have been presented, highlighting similarities and differences
      to the classical PDGFs. In this paper we review the published data on the PDGF
      family covering structural (gene and protein) similarities and differences among
      all four family members, with special focus on PDGF-C and PDGF-D expression and
      functions. Little information on the protein structures of PDGF-C and -D is
      currently available, but the PDGF-C protein may be structurally more similar to
      VEGF-A than to PDGF-B. PDGF-C contributes to normal development of the heart,
      ear, central nervous system (CNS), and kidney, while PDGF-D is active in the
      development of the kidney, eye and brain. In adults, PDGF-C is active in the
      kidney and the central nervous system. PDGF-D also plays a role in the lung and
      in periodontal mineralization. PDGF-C is expressed in Ewing family sarcoma and
      PDGF-D is linked to lung, prostate and ovarian cancers. Both PDGF-C and -D play a
      role in progressive renal disease, glioblastoma/medulloblastoma and fibrosis in
      several organs.

PMID- 16279936
TI  - Prokineticin 2 and circadian clock output.
AB  - Circadian timing from the suprachiasmatic nucleus (SCN) is a critical component
      of sleep regulation. Animal lesion and genetic studies have indicated an
      essential interaction between the circadian signals and the homeostatic processes
      that regulate sleep. Here we summarize the biological functions of prokineticins,
      a pair of newly discovered regulatory proteins, with focus on the circadian
      function of prokineticin 2 (PK2) and its potential role in sleep-wake regulation.
      PK2 has been shown as a candidate SCN output molecule that regulates circadian
      locomotor behavior. The PK2 molecular rhythm in the SCN is predominantly
      controlled by the circadian transcriptional/translational loops, but also
      regulated directly by light. The receptor for PK2 is expressed in the primary SCN
      output targets that regulate circadian behavior including sleep-wake. The
      depolarizing effect of PK2 on neurons that express PK2 receptor may represent a
      possible mechanism for the regulatory role of PK2 in circadian rhythms.

PMID- 16279939
TI  - Activation of the plasma membrane H-ATPase of Saccharomyces cerevisiae by glucose
      is mediated by dissociation of the H(+)-ATPase-acetylated tubulin complex.
AB  - In the yeast Saccharomyces cerevisiae, plasma membrane H(+)-ATPase is activated
      by d-glucose. We found that in the absence of glucose, this enzyme forms a
      complex with acetylated tubulin. Acetylated tubulin usually displays hydrophilic
      properties, but behaves as a hydrophobic compound when complexed with H(+)
      ATPase, and therefore partitions into a detergent phase. When cells were treated
      with glucose, the H(+)-ATPase-tubulin complex was disrupted, with two
      consequences, namely (a) the level of acetylated tubulin in the plasma membrane
      decreased as a function of glucose concentration and (b) the H(+)-ATPase activity
      increased as a function of glucose concentration, as measured by both ATP
      hydrolyzing capacity and H(+)-pumping activity. The addition of 2-deoxy-d-glucose
      inhibited the above glucose-induced phenomena, suggesting the involvement of
      glucose transporters. Whereas total tubulin is distributed uniformly throughout
      the cell, acetylated tubulin is concentrated near the plasma membrane. Results
      from immunoprecipitation experiments using anti-(acetylated tubulin) and anti
      (H(+)-ATPase) immunoglobulins indicated a physical interaction between H(+)
      ATPase and acetylated tubulin in the membranes of glucose-starved cells. When
      cells were pretreated with 1 mm glucose, this interaction was disrupted. Double
      immunofluorescence, observed by confocal microscopy, indicated that H(+)-ATPase
      and acetylated tubulin partially colocalize at the periphery of glucose-starved
      cells, with predominance at the outer and inner sides of the membrane,
      respectively. Colocalization was not observed when cells were pretreated with 1
      mm glucose, reinforcing the idea that glucose treatment produces dissociation of
      the H(+)-ATPase-tubulin complex. Biochemical experiments using isolated membranes
      from yeast and purified tubulin from rat brain demonstrated inhibition of H(+)
      ATPase activity by acetylated tubulin and concomitant increase of the H(+)-ATP
      ase-tubulin complex.

PMID- 16279940
TI  - End-damage-specific proteins facilitate recruitment or stability of X-ray cross
      complementing protein 1 at the sites of DNA single-strand break repair.
AB  - Ionizing radiation, oxidative stress and endogenous DNA-damage processing can
      result in a variety of single-strand breaks with modified 5' and/or 3' ends.
      These are thought to be one of the most persistent forms of DNA damage and may
      threaten cell survival. This study addresses the mechanism involved in
      recognition and processing of DNA strand breaks containing modified 3' ends.
      Using a DNA-protein cross-linking assay, we followed the proteins involved in the
      repair of oligonucleotide duplexes containing strand breaks with a phosphate or
      phosphoglycolate group at the 3' end. We found that, in human whole cell
      extracts, end-damage-specific proteins (apurinic/apyrimidinic endonuclease 1 and
      polynucleotide kinase in the case of 3' ends containing phosphoglycolate and
      phosphate, respectively) which recognize and process 3'-end-modified DNA strand
      breaks are required for efficient recruitment of X-ray cross-complementing
      protein 1-DNA ligase IIIalpha heterodimer to the sites of DNA repair.

PMID- 16279941
TI  - Metabolic control analysis reveals an important role for diacylglycerol
      acyltransferase in olive but not in oil palm lipid accumulation.
AB  - We applied metabolic control analysis to the Kennedy pathway for triacylglycerol
      formation in tissue cultures from the important oil crops, olive (Olea europaea
      L.) and oil palm (Elaeis guineensis Jacq.). When microsomal fractions were
      incubated at 30 degrees C rather than 20 degrees C, there was an increase in
      triacylglycerol labelling. This increase was accompanied by a build up of
      diacylglycerol (DAG) radioactivity in olive but not in oil palm, suggesting that
      the activity of DAG acyltransferase (DAGAT) was becoming limiting in olive. We
      used 2-bromooctanoate as a specific inhibitor of DAGAT and showed that the enzyme
      had a flux control coefficient under the experimental conditions of 0.74 in olive
      but only 0.12 in oil palm. These data revealed important differences in the
      regulation of lipid biosynthesis in cultures from different plants and suggest
      that changes in the endogenous activity of DAGAT is unlikely to affect oil
      accumulation in oil palm crops.

PMID- 16279942
TI  - Nerve influence on myosin light chain phosphorylation in slow and fast skeletal
      muscles.
AB  - Neural stimulation controls the contractile properties of skeletal muscle fibres
      through transcriptional regulation of a number of proteins, including myosin
      isoforms. To study whether neural stimulation is also involved in the control of
      post-translational modifications of myosin, we analysed the phosphorylation of
      alkali myosin light chains (MLC1) and regulatory myosin light chains (MLC2) in
      rat slow (soleus) and fast (extensor digitorum longus EDL) muscles using 2D-gel
      electrophoresis and mass spectrometry. In control rats, soleus and EDL muscles
      differed in the proportion of the fast and slow isoforms of MLC1 and MLC2 that
      they contained, and also in the distribution of the variants with distinct
      isoelectric points identified on 2D gels. Denervation induced a slow-to-fast
      transition in myosin isoforms and increased MLC2 phosphorylation in soleus,
      whereas the opposite changes in myosin isoform expression and MLC2
      phosphorylation were observed in EDL. Chronic low-frequency stimulation of EDL,
      with a pattern mimicking that of soleus, induced a fast-to-slow transition in
      myosin isoforms, accompanied by a decreased MLC2 phosphorylation. Chronic
      administration (10 mg x kg(-1) x d(-1) intraperitoneally) of cyclosporin A, a
      known inhibitor of calcineurin, did not change significantly the distribution of
      fast and slow MLC2 isoforms or the phosphorylation of MLC2. All changes in MLC2
      phosphorylation were paralleled by changes in MLC kinase expression without any
      variation of the phosphatase subunit, PP1. No variation in MLC1 phosphorylation
      was detectable after denervation or cyclosporin A administration. These results
      suggest that the low-frequency neural discharge, typical of soleus, determines
      low levels of MLC2 phosphorylation together with expression of slow myosin, and
      that MLC2 phosphorylation is regulated by controlling MLC kinase expression
      through calcineurin-independent pathways.

PMID- 16279943
TI  - Molecular analysis of the interaction between cardosin A and phospholipase
      D(alpha). Identification of RGD/KGE sequences as binding motifs for C2 domains.
AB  - Here we report the identification of phospholipase Dalpha as a cardosin A-binding
      protein. The interaction was confirmed by coimmunoprecipitation studies and pull
      down assays. To investigate the structural and molecular determinants involved in
      the interaction, pull-down assays with cardosin A and various glutathione S
      transferase-fused phospholipase Dalpha constructs were performed. Results
      revealed that the C2 domain of phospholipase Dalpha contains the cardosin A
      binding activity. Further assays with mutated recombinant forms of cardosin A
      showed that the RGD motif as well as the unprecedented KGE motif, which is
      structurally and charge-wise very similar to RGD, are indispensable for the
      interaction. Taken together our results indicate that the C2 domain of plant
      phospholipase Dalpha can act as a cardosin A-binding domain and suggest that
      plant C2 domains may have an additional role as RGD/KGE-recognition domains.

PMID- 16279944
TI  - Crystal structure of the beta-chain of human hepatocyte growth factor
      like/macrophage stimulating protein.
AB  - Hepatocyte growth factor like/macrophage stimulating protein (HGFl/MSP) and
      hepatocyte growth factor/scatter factor (HGF/SF) define a distinct family of
      vertebrate-specific growth factors structurally related to the blood proteinase
      precursor plasminogen and with important roles in development and cancer.
      Although the two proteins share a similar domain structure and mechanism of
      activation, there are differences between HGFl/MSP and HGF/SF in terms of the
      contribution of individual domains to receptor binding. Here we present a crystal
      structure of the 30 kDa beta-chain of human HGFl/MSP, a serine proteinase
      homology domain containing the high-affinity binding site for the RON receptor.
      The structure describes at 1.85 Angstrom resolution the region of the domain
      corresponding to the receptor binding site recently defined in the HGF/SF beta
      chain, namely the central cleft harboring the three residues corresponding to the
      catalytic ones of active proteinases (numbers in brackets define the sequence
      position according to the standard chymotrypsinogen numbering system) [Gln522
      (c57), Gln568 (c102) and Tyr661 (c195)] and an adjacent loop flanking the S1
      specificity pocket and containing residues Asn682 (c217) and Arg683 (c218)
      previously shown to be essential for binding of HGFl/MSP to the RON receptor. The
      study confirms the concept that the serine proteinase homology domains of
      HGFl/MSP and HGF/SF bind their receptors in an 'enzyme-substrate' mode,
      reflecting the common evolutionary origin of the plasminogen-related growth
      factors and the proteinases of the clotting and fibrinolytic pathways. However,
      analysis of the intermolecular interactions in the crystal lattice of beta-chain
      HGFl/MSP fails to show the same contacts seen in the HGF/SF structures and does
      not support a conserved mode of dimerization of the serine proteinase homology
      domains of HGFl/MSP and HGF/SF responsible for receptor activation.

PMID- 16279945
TI  - Shedding of the amyloid precursor protein-like protein APLP2 by disintegrin
      metalloproteinases.
AB  - Cleavage of the amyloid precursor protein (APP) within the amyloid-beta (Abeta)
      sequence by the alpha-secretase prevents the formation of toxic Abeta peptides.
      It has been shown that the disintegrin-metalloproteinases ADAM10 and TACE
      (ADAM17) act as alpha-secretases and stimulate the generation of a soluble
      neuroprotective fragment of APP, APPsalpha. Here we demonstrate that the related
      APP-like protein 2 (APLP2), which has been shown to be essential for development
      and survival of mice, is also a substrate for both proteinases. Overexpression of
      either ADAM10 or TACE in HEK293 cells increased the release of neurotrophic
      soluble APLP2 severalfold. The strongest inhibition of APLP2 shedding in
      neuroblastoma cells was observed with an ADAM10-preferring inhibitor. Transgenic
      mice with neuron-specific overexpression of ADAM10 showed significantly increased
      levels of soluble APLP2 and its C-terminal fragments. To elucidate a possible
      regulatory mechanism of APLP2 shedding in the neuronal context, we examined
      retinoic acid-induced differentiation of neuroblastoma cells. Retinoic acid
      treatment of two neuroblastoma cell lines upregulated the expression of both
      APLP2 and ADAM10, thus leading to an increased release of soluble APLP2.

PMID- 16279946
TI  - Induction of PAI-1 expression by tumor necrosis factor alpha in endothelial cells
      is mediated by its responsive element located in the 4G/5G site.
AB  - Plasminogen activator inhibitor type 1 (PAI-1) is induced by many proinflammatory
      and pro-oxidant factors. Among them, tumor necrosis factor alpha (TNFalpha), a
      pivotal early mediator that regulates and amplifies the development of
      inflammation, is one of the strongest PAI-1 synthesis activators. Location of the
      TNFalpha response element in the PAI-1 promoter is still ambiguous. In this
      study, we attempted to evaluate the significance of the element located in the
      4G/5G site of the PAI-1 promoter in the TNFalpha stimulation of PAI-1 expression
      in endothelial cells. PAI-1 expression was monitored at: (a) the level of mRNA
      using real-time PCR, (b) PAI-1 gene transcription by transfection reporter
      assays, and (c) protein synthesis using the enzyme immunoassay. NF-kappaB
      activity was monitored using the electrophoretic mobility shift assay. Its
      activity was modified by either antisense oligonucleotides or transfection of
      endothelial cells with the wild-type or mutated IkappaBalpha. We have shown that
      TNFalpha-induced expression and gene transcription of PAI-1 involves a regulatory
      region present in segment -664/-680 of the PAI-1 promoter. This reaction involves
      the TNFalpha-induced generation of superoxide leading to activation of NF-kappaB,
      and can be abolished by antioxidants and by overexpression of a super-suppressor
      phosphorylation-resistant IkappaBalpha. Stimulation of PAI-1 under these
      conditions involves the motif of the PAI-1 promoter adjacent to the 4G/5G site,
      which can directly interact with NF-kappaB. We show that activation of PAI-1 gene
      by TNFalpha and reactive oxygen species is mediated by interaction of NF-kappaB
      with the cis-acting element located in the -675 4G/5G insertion/deletion in the
      PAI-1 promoter.

PMID- 16279947
TI  - Molecular identification of adrenal inner zone antigen as a heme-binding protein.
AB  - The adrenal inner zone antigen (IZA), which reacts specifically with a monoclonal
      antibody raised against the fasciculata and reticularis zones of the rat adrenal,
      was previously found to be identical with a protein variously named 25-Dx and
      membrane-associated progesterone receptor. IZA was purified as a glutathione S
      transferase-fused or His(6)-fused protein, and its molecular properties were
      studied. The UV-visible absorption and EPR spectra of the purified protein showed
      that IZA bound a heme chromophore in high-spin type. Analysis of the heme
      indicated that it is of the b type. Site-directed mutagenesis studies were
      performed to identify the amino-acid residues that bind the heme to the protein.
      The results suggest that two Tyr residues, Tyr107 and Tyr113, and a peptide
      stretch, D99-K102, were important for anchoring the heme into a hydrophobic
      pocket. The effect of IZA on the steroid 21-hydroxylation reaction was
      investigated in COS-7 cell expression systems. The results suggest that the
      coexistence of IZA with CYP21 enhances 21-hydroxylase activity.

PMID- 16279948
TI  - Ca(2+) rise within a narrow window of concentration prevents functional injury of
      mitochondria exposed to hypoxia/reoxygenation by increasing antioxidative
      defence.
AB  - Injury of liver by ischaemia crucially involves mitochondrial damage. The role of
      Ca(2+) in mitochondrial damage is still unclear. We investigated the effect of
      low micromolar Ca(2+) concentrations on respiration, membrane permeability, and
      antioxidative defence in liver mitochondria exposed to hypoxia/reoxygenation.
      Hypoxia/reoxygenation caused decrease in state 3 respiration and in the
      respiratory control ratio. Liver mitochondria were almost completely protected at
      about 2 microM Ca(2+). Below and above 2 microM Ca(2+), mitochondrial function
      was deteriorated, as indicated by the decrease in respiratory control ratio.
      Above 2 microM Ca(2+), the mitochondrial membrane was permeabilized, as
      demonstrated by the sensitivity of state 3 respiration to NADH. Below 2 microM
      Ca(2+), the nitric oxide synthase inhibitor nitro-l-arginine methylester had a
      protective effect. The activities of the manganese superoxide dismutase and
      glutathione peroxidase after hypoxia showed maximal values at about 2 microM
      Ca(2+). We conclude that Ca(2+) exerts a protective effect on mitochondria within
      a narrow concentration window, by increasing the antioxidative defence.

PMID- 16279950
TI  - Characterization of the interaction between the plasma membrane H-ATPase of
      Arabidopsis thaliana and a novel interactor (PPI1).
AB  - Proton pump interactor, isoform 1 (PPI1) is a novel interactor of the C-terminus
      of Arabidopsis thaliana plasma membrane H(+)-ATPase (EC 3.6.3.6). We produced two
      fusion proteins consisting of, respectively, the first 88 amino acids or the
      entire protein deleted of the last 24 hydrophobic amino acids, and we show that
      the latter protein has a threefold higher affinity for the H(+)-ATPase. PPI1
      induced stimulation of H(+)-ATPase activity dramatically decreased with the
      increase of pH above pH 6.8, but became largely pH-independent when the enzyme C
      terminus was displaced by fusicoccin-induced binding of 14-3-3 proteins. The
      latter treatment did not affect PPI1 affinity for the H(+)-ATPase. These results
      indicate that PPI1 can bind the H(+)-ATPase independently of the C-terminus
      conformation, but is not able to suppress the C-terminus auto-inhibitory action.

PMID- 16279949
TI  - Chromosomal protein HMGN1 modulates the expression of N-cadherin.
AB  - HMGN1 is a nuclear protein that binds to nucleosomes and alters the accessibility
      of regulatory factors to their chromatin targets. To elucidate its biological
      function and identify specific HMGN1 target genes, we generated Hmgn1-/- mice.
      DNA microarray analysis of Hmgn1+/+ and Hmgn1-/- embryonic fibroblasts identified
      N-cadherin as a potential HMGN1 gene target. RT-PCR and western blot analysis
      confirmed a linkage between HMGN1 expression and N-cadherin levels. In both
      transformed and primary mouse embryonic fibroblasts (MEFs), HMGN1 acted as
      negative regulator of N-cadherin expression. Likewise, the N-cadherin levels in
      early embryos of Hmgn1-/- mice were higher than those of their Hmgn1+/+
      littermates. Loss of HMGN1 increased the adhesiveness, motility and aggregation
      potential of Hmgn1-/- MEFs, a phenotype consistent with increased levels of N
      cadherin protein. Re-expression of wild-type HMGN1, but not of the mutant HMGN1
      protein that does not bind to chromatin, in Hmgn1-/- MEFs, decreased the levels
      of N-cadherin and restored the Hmgn1+/+ phenotype. These studies demonstrate a
      role for HMGN1 in the regulation of specific gene expression. We suggest that in
      MEFs, and during early mouse development, the interaction of HMGN1 with chromatin
      down-regulates the expression of N-cadherin.

PMID- 16279951
TI  - His374 of wheat endoxylanase inhibitor TAXI-I stabilizes complex formation with
      glycoside hydrolase family 11 endoxylanases.
AB  - Wheat endoxylanase inhibitor TAXI-I inhibits microbial glycoside hydrolase family
      11 endoxylanases. Crystallographic data of an Aspergillus niger endoxylanase-TAXI
      I complex showed His374 of TAXI-I to be a key residue in endoxylanase inhibition.
      Its role in enzyme-inhibitor interaction was further investigated by site
      directed mutagenesis of His374 into alanine, glutamine or lysine. Binding
      kinetics and affinities of the molecular interactions between A. niger, Bacillus
      subtilis, Trichoderma longibrachiatumendoxylanases and wild-type TAXI-I and TAXI
      I His374 mutants were determined by surface plasmon resonance analysis. Enzyme
      inhibitor binding was in accordance with a simple 1 : 1 binding model.
      Association and dissociation rate constants of wild-type TAXI-I towards the
      endoxylanases were in the range between 1.96 and 36.1 x 10(4)m(-1) x s(-1) and
      0.72-3.60 x 10(-4) x s(-1), respectively, resulting in equilibrium dissociation
      constants in the low nanomolar range. Mutation of TAXI-I His374 to a variable
      degree reduced the inhibition capacity of the inhibitor mainly due to higher
      complex dissociation rate constants (three- to 80-fold increase). The association
      rate constants were affected to a smaller extent (up to eightfold decrease).
      Substitution of TAXI-I His374 therefore strongly affects the affinity of the
      inhibitor for the enzymes. In addition, the results show that His374 plays a
      critical role in the stabilization of the endoxylanase-TAXI-I complex rather than
      in the docking of inhibitor onto enzyme.

PMID- 16279952
TI  - Oxidized elafin and trappin poorly inhibit the elastolytic activity of neutrophil
      elastase and proteinase 3.
AB  - Neutrophil proteinase-mediated lung tissue destruction is prevented by
      inhibitors, including elafin and its precursor, trappin. We wanted to establish
      whether neutrophil-derived oxidants might impair the inhibitory function of these
      molecules. Myeloperoxidase/H(2)O(2) and N-chlorosuccinimide oxidation of the
      inhibitors was checked by mass spectrometry and enzymatic methods. Oxidation
      significantly lowers the affinities of the two inhibitors for neutrophil elastase
      (NE) and proteinase 3 (Pr3). This decrease in affinity is essentially caused by
      an increase in the rate of inhibitory complex dissociation. Oxidized elafin and
      trappin have, however, reasonable affinities for NE (K(i) = 4.0-9.2 x 10(-9) M)
      and for Pr3 (K(i) = 2.5-5.0 x 10(-8) M). These affinities are theoretically
      sufficient to allow the oxidized inhibitors to form tight binding complexes with
      NE and Pr3 in lung secretions where their physiological concentrations are in the
      micromolar range. Yet, they are unable to efficiently inhibit the elastolytic
      activity of the two enzymes. At their physiological concentration, fully oxidized
      elafin and trappin do not inhibit more than 30% of an equimolar concentration of
      NE or Pr3. We conclude that in vivo oxidation of elafin and trappin strongly
      impairs their activity. Inhibitor-based therapy of inflammatory lung diseases
      must be carried out using oxidation-resistant variants of these molecules.

PMID- 16279953
TI  - Tryptophan tryptophylquinone cofactor biogenesis in the aromatic amine
      dehydrogenase of Alcaligenes faecalis. Cofactor assembly and catalytic properties
      of recombinant enzyme expressed in Paracoccus denitrificans.
AB  - The heterologous expression of tryptophan trytophylquinone (TTQ)-dependent
      aromatic amine dehydrogenase (AADH) has been achieved in Paracoccus
      denitrificans. The aauBEDA genes and orf-2 from the aromatic amine utilization
      (aau) gene cluster of Alcaligenes faecalis were placed under the regulatory
      control of the mauF promoter from P. denitrificans and introduced into P.
      denitrificans using a broad-host-range vector. The physical, spectroscopic and
      kinetic properties of the recombinant AADH were indistinguishable from those of
      the native enzyme isolated from A. faecalis. TTQ biogenesis in recombinant AADH
      is functional despite the lack of analogues in the cloned aau gene cluster for
      mauF, mauG, mauL, mauM and mauN that are found in the methylamine utilization
      (mau) gene cluster of a number of methylotrophic organisms. Steady-state reaction
      profiles for recombinant AADH as a function of substrate concentration differed
      between 'fast' (tryptamine) and 'slow' (benzylamine) substrates, owing to a lack
      of inhibition by benzylamine at high substrate concentrations. A deflated and
      temperature-dependent kinetic isotope effect indicated that C-H/C-D bond breakage
      is only partially rate-limiting in steady-state reactions with benzylamine.
      Stopped-flow studies of the reductive half-reaction of recombinant AADH with
      benzylamine demonstrated that the KIE is elevated over the value observed in
      steady-state turnover and is independent of temperature, consistent with (a)
      previously reported studies with native AADH and (b) breakage of the substrate C
      H bond by quantum mechanical tunnelling. The limiting rate constant (k(lim)) for
      TTQ reduction is controlled by a single ionization with pK(a) value of 6.0, with
      maximum activity realized in the alkaline region. Two kinetically influential
      ionizations were identified in plots of k(lim)/K(d) of pK(a) values 7.1 and 9.3,
      again with the maximum value realized in the alkaline region. The potential
      origin of these kinetically influential ionizations is discussed.

PMID- 16279954
TI  - Hairpin ribozymes in combination with siRNAs against highly conserved hepatitis C
      virus sequence inhibit RNA replication and protein translation from hepatitis C
      virus subgenomic replicons.
AB  - Chronic hepatitis C virus (HCV) infection is a clinically important liver disease
      with limited therapeutic options in a significant proportion of patients.
      Therefore, novel efficient therapeutic agents are needed. Because the 5'- and 3'
      untranslated regions (UTRs) of HCV are highly conserved and functionally
      important for HCV replication, they are attractive targets for RNA-cleaving
      ribozymes or small interfering RNAs (siRNAs). In this study hairpin ribozymes
      (Rz) targeting HCV 5'- and 3'-UTR sequences were expressed from a retroviral
      vector transcript under control of two different RNA polIII promoters (tRNA(Val),
      U6). Ribozymes were evaluated in monocistronic, subgenomic I389/hyg-ubi/NS3
      3'/5.1 HCV replicon cells as single agents or in combination with siRNAs against
      HCV 5'- or 3'-UTR recently demonstrated to inhibit HCV replicons. Additionally,
      ribozyme constructs were generated with the 3'-terminus of the ribozyme flanked
      by constitutive transport element (CTE) sequences, an RNA motif that has
      previously been shown to enhance cleavage activity of hammerhead ribozymes. In
      our study, tRNA(Val) as well as U6 promoter-driven Rzs markedly reduced HCV
      replicon RNA expression and HCV internal ribosome entry site (IRES)-mediated HCV
      NS5B protein translation from monocistronic subgenomic replicons. However,
      attachment of CTE sequences to the 3'-terminus did not significantly enhance
      activity of Rzs tested in this study. Interestingly, we detected additive HCV
      inhibitory effects for combinations of tRNA(Val)-driven Rzs and U6-derived siRNAs
      both directed against highly conserved 5'- and 3'-UTR sequence, suggesting that a
      dual strategy of ribozymes and siRNAs might become a powerful molecular tool to
      specifically silence HCV RNA replication.

PMID- 16279955
TI  - A complete survey of Trichoderma chitinases reveals three distinct subgroups of
      family 18 chitinases.
AB  - Genome-wide analysis of chitinase genes in the Hypocrea jecorina (anamorph:
      Trichoderma reesei) genome database revealed the presence of 18 ORFs encoding
      putative chitinases, all of them belonging to glycoside hydrolase family 18.
      Eleven of these encode yet undescribed chitinases. A systematic nomenclature for
      the H. jecorina chitinases is proposed, which designates the chitinases
      corresponding to their glycoside hydrolase family and numbers the isoenzymes
      according to their pI from Chi18-1 to Chi18-18. Phylogenetic analysis of H.
      jecorina chitinases, and those from other filamentous fungi, including
      hypothetical proteins of annotated fungal genome databases, showed that the
      fungal chitinases can be divided into three groups: groups A and B (corresponding
      to class V and III chitinases, respectively) also contained the so Trichoderma
      chitinases identified to date, whereas a novel group C comprises high molecular
      weight chitinases that have a domain structure similar to Kluyveromyces lactis
      killer toxins. Five chitinase genes, representing members of groups A-C, were
      cloned from the mycoparasitic species H. atroviridis (anamorph: T. atroviride).
      Transcription of chi18-10 (belonging to group C) and chi18-13 (belonging to a
      novel clade in group B) was triggered upon growth on Rhizoctonia solani cell
      walls, and during plate confrontation tests with the plant pathogen R. solani.
      Therefore, group C and the novel clade in group B may contain chitinases of
      potential relevance for the biocontrol properties of Trichoderma.

PMID- 16279957
TI  - The economics of public health and medical care. 1932.

PMID- 16279958
TI  - The American approach to health insurance. 1934.

PMID- 16279959
TI  - The relationship of the Milbank Memorial Fund to the field of health and the
      medical profession. 1935.

PMID- 16279961
TI  - Nutrition in war and peace. 1947.

PMID- 16279960
TI  - Population trends and problems of public health. 1940.

PMID- 16279962
TI  - Mental hygiene and socio-environmental factors. 1948.

PMID- 16279963
TI  - Longitudinal analyses of four years of experience of a prepaid comprehensive
      medical care plan. 1958.

PMID- 16279964
TI  - Evaluating the quality of medical care. 1966.

PMID- 16279965
TI  - The epidemiologic transition: a theory of the epidemiology of population change.
      1971.

PMID- 16279966
TI  - The organization of personal health services. 1972.

PMID- 16279967
TI  - The failures of success. 1977.

PMID- 16279968
TI  - The compression of morbidity. 1983.

PMID- 16279969
TI  - "The high cost of dying": what do the data show? 1984.

PMID- 16279971
TI  - Supporting e-learners in healthcare.

PMID- 16279970
TI  - How good is the quality of health care in the United States? 1998.

PMID- 16279973
TI  - Effective e-learning for health professionals and students--barriers and their
      solutions. A systematic review of the literature--findings from the HeXL project.
AB  - INTRODUCTION: In 2003/4 the Information Management Research Institute,
      Northumbria University, conducted a research project to identify the barriers to
      e-learning for health professionals and students. The project also established
      possible ways to overcome these barriers. The North of England Workforce
      Development Confederation funded the project. METHODOLOGY: The project comprised
      a systematic review of the literature on barriers to and solutions/critical
      success factors for e-learning in the health field. Fifty-seven references were
      suitable for analysis. This review was supplemented by a questionnaire survey of
      learners and an interview study of learning providers to ensure that data
      identified from the literature were grounded in reality. RESULTS: The main
      barriers are: requirement for change; costs; poorly designed packages; inadequate
      technology; lack of skills; need for a component of face-to-face teaching; time
      intensive nature of e-learning; computer anxiety. A range of solutions can solve
      these barriers. The main solutions are: standardization; strategies; funding;
      integration of e-learning into the curriculum; blended teaching; user friendly
      packages; access to technology; skills training; support; employers paying e
      learning costs; dedicated work time for e-learning. CONCLUSIONS: The authors
      argue that librarians can play an important role in e-learning: providing support
      and support materials; teaching information skills; managing and providing access
      to online information resources; producing their own e-learning packages;
      assisting in the development of other packages.

PMID- 16279972
TI  - Studying health information from a distance: refining an e-learning case study in
      the crucible of student evaluation.
AB  - PURPOSE: To present a formative evaluation of the impact of a multimedia case
      study as a component of a masters course in health informatics delivered by
      distance learning. SETTING/PARTICIPANTS/RESOURCES: First and second year health
      informatics students undertaking four core modules of a masters programme at the
      University of Sheffield. METHODOLOGY: Individual qualitative user surveys and
      interviews. RESULTS/OUTCOMES: Formative evaluation has played a significant role
      in refining the case study through its text-based, intermediate and CD-ROM based
      stages. Feedback from students has resulted in clarification of case study tasks,
      clearer definition of teaching roles and a revised approach to assessment. At the
      same time it has highlighted the importance of ongoing revision and maintenance
      in keeping the scenarios realistic and current. DISCUSSION/CONCLUSION: The
      multimedia case study has met many of its original aims in providing greater
      cohesion for core modules and encouraging greater levels of interaction and
      multidisciplinary collaboration.

PMID- 16279974
TI  - A strategic approach to developing e-learning capability for healthcare.
AB  - OBJECTIVES: This article examines a strategic approach to developing e-learning
      capability to enhance learning opportunities for the workforce of a healthcare
      organization. Emphasis is given to the procurement of a bespoke Managed Learning
      Environment (MLE). Strategic organizational issues impacting on future e-learning
      developments are considered. METHODS: The 2-year implementation plan was
      evaluated through a two phase external research project. The first phase focused
      on the effectiveness of a training programme designed to build capacity for e
      learning within the Northern area and also included a virtual learning
      environment usability study which informed the MLE specification. The second
      phase evaluation is ongoing during 2005 and interim findings are presented.
      RESULTS: The MLE has been piloted and on-line learning packages have been
      acquired. There has been a phased take-up of e-learning opportunities and e-tutor
      training. Some virtual Communities of Practice have been established. Key
      organizational issues have been identified and ongoing findings are informing
      strategic planning. CONCLUSIONS: The healthcare MLE is offering enhanced learning
      opportunities and assisting area healthcare providers in training their dispersed
      workforces. Blended learning strategies are most successful. The need for
      protected time for e-learning is a key issue, financial savings are available.
      Progress has been slowed by identified organizational constraints-the MLE's
      benefits are widely recognized.

PMID- 16279975
TI  - Healthcare librarians and learner support: a review of competences and methods.
AB  - OBJECTIVES: London Health Libraries (LHL) are undertaking a project in order to
      develop the role of their library and knowledge services staff in supporting
      learners within the NHS in the London area (LHL Learner Support Project). This
      paper reports on the first phase of the project. METHODOLOGY: A literature
      analysis was carried out to provide guidance on the skills and competences needed
      for library and knowledge staff to perform this function. RESULTS: A variety of
      competences are identified, and structured in a model incorporating both training
      skills and general professional competencies. Library and knowledge staff will
      themselves need to have a high-level of information literacy and to be active
      lifelong learners. CONCLUSIONS: A 'blended learning' approach, involving e
      learning together with other methods, is identified as the most appropriate way
      for skills to be acquired.

PMID- 16279976
TI  - Using mobile technologies to give health students access to learning resources in
      the UK community setting.
AB  - OBJECTIVES: This article describes a project which explored the potential for
      mobile technologies to give health students in the community access to learning
      resources. The purpose included the need to identify possible barriers students
      could face in using mobile technologies. Another focus was to assess the students
      perceptions of the importance of being able to access learning resources in the
      community. METHODS: This 1-year project used two main approaches for data
      collection. A review of the literature on mobile technologies in the health
      context was conducted. This was used in a systematic way to identify key issues
      and trends. The literature review was used to inform the design and production of
      a questionnaire. This was distributed to and completed by a group of community
      health students at Northumbria University, UK. The questionnaire was piloted and
      there was a 100% completion rate with 49 returned forms. RESULTS: The literature
      review indicated that most mobile technology applications were occurring in the
      US. At the time of the review the most prevalent mobile technologies were PDAs,
      laptops, WAP phones and portable radios with use being concentrated around
      doctors in the acute sector. A range of advantages and disadvantages to the
      technology were discovered. Mobile technologies were mainly being used for
      clinical rather than learning applications. The students showed a low level of
      awareness of the technology but placed great importance to accessing learning
      resources from the community. CONCLUSIONS: Significant development and changes
      are taking place in mobile technologies. Since the data collection for this work
      was completed in 2004 podcasting and videocasting have become significant in
      mobile learning for health professionals. Librarians will need to address the
      relevance and implications of m-learning for their practice. Care and
      consideration needs to be given on the time and resources librarians allocate for
      the necessary development work around mobile technologies. Collaboration and
      partnership working will be most effective approach for librarians wishing to
      integrate their services with m-learning technologies.

PMID- 16279977
TI  - Implementation of e-learning and the teaching hospital: a local perspective.

PMID- 16279978
TI  - Learning and teaching resource discovery in the Health and Life Sciences-
      partnership and interoperability.

PMID- 16279979
TI  - E-learning in the common learning curriculum for health and social care
      professionals: information literacy and the library.

PMID- 16279980
TI  - A little e-learning can go a long way in transforming a traditional print-based
      distance learning course: a case study at the UK's Open University.

PMID- 16279981
TI  - e-FOLIO: using e-learning to learn about e-learning.

PMID- 16279983
TI  - Electrophysiological findings of peripheral neuropathy in newly diagnosed type II
      diabetes mellitus.
AB  - This study was aimed at assessing the electrophysiological signs of peripheral
      neuropathy in diabetes mellitus (DM) type II patients at diagnosis. Nerve
      conduction studies (NCS) of median, ulnar, peroneal, tibial and sural nerves were
      performed in 39 newly diagnosed DM subjects and compared to those of 40 healthy
      controls. Metabolic indices were also investigated. Electrophysiological
      alterations were found in 32 (82%) of the DM patients, and more than half of them
      (62.2%) showed multiple (two to five) abnormal parameters. Because most of the
      subjects (84.4%) had from two to five nerves involved, these alterations were
      widespread in the seven nerves evaluated. Forty-two percent of the patients had
      NCS alterations suggestive of distal median mononeuropathy, implying that
      metabolic factors in DM make the median nerve more susceptible to focal
      entrapment. A reduced sensory nerve action potential (SNAP) amplitude was
      observed in the median nerve in 70% of the patients, in the ulnar in 69% and in
      the sural nerve only in 22%. In the presence of a decrease in the SNAP amplitude
      of the ulnar or median nerve, the SNAP amplitude of the sural nerve was normal in
      82 or 80% of the subjects, respectively. This finding may be in keeping with a
      distal involvement of the sensory fibres, as explored by routine median or ulnar
      NCS. No correlation was found between metabolic indices and NCS parameters. In
      conclusion, a high percentage of newly diagnosed DM patients show signs of
      neuropathy, and upper limb nerve sensory NCS seem to be more sensitive in
      detecting it than lower limb NCS.

PMID- 16279984
TI  - Obesity and peripheral neuropathy risk: a dangerous liaison.
AB  - This study investigates motor (MNCS) and sensory (SNCS) nerve conduction in a
      sample of non-diabetic obese people without symptoms suggestive of neuropathy and
      looks for a possible metabolic alteration. Twenty-one patients and 20 age-matched
      controls underwent (a) MNCS (median, ulnar, peroneal, and tibial) and SNCS
      (median, ulnar, and sural); (b) quantitative sensory testing to measure sensory
      threshold for vibration, warm and cold sensation (WS-CS), heat and cold-induced
      pain; and (c) blood sample analysis to evaluate glucose and insulin levels and
      calculate the quantitative insulin-sensitivity check index (QUICKI). The obese
      group showed significantly decreased compound muscle action potential amplitude
      of tibial and peroneal nerves and decreased sensory action potential amplitude of
      all nerves. Most of the sensory thresholds were altered in obese patients.
      Insulin serum levels were significantly increased while QUICKI decreased in obese
      patients. WS and CS from the index and little fingers and WS from the big toe
      significantly correlated with QUICKI. Thermal and pain thresholds from the index
      and thermal thresholds from the little finger correlated with QUICKI values. The
      non-diabetic obese patients showed a subclinical involvement of different
      diameter sensory fibers. Such impairment was related to hyperinsulinemia and
      insulin sensitivity. The increase in sensory threshold of obese patients might be
      due to a metabolic alteration, potentially leading to a future clinical
      neuropathy.

PMID- 16279985
TI  - The course of aberrant reinnervation following nerve repair with fresh or
      denatured muscle autografts.
AB  - Denatured muscle grafts obtained by freeze thawing have been proposed to replace
      losses in the peripheral nerves. In the present report, we compare the
      performance of such grafts with fresh grafts in the rat median nerve. A long-term
      effect of muscle interposition on reinnervation was studied by behavioral
      assessment, muscle ATPase histochemistry, and retrograde labeling of motoneurons.
      There was no difference in grasping strength recovery between fresh and denatured
      10-mm-long muscle grafts. Recovery was delayed and incomplete. Twelve months
      after surgery, only 50% of the normal grasping strength was attained. Grasping
      recovery was not observed in the 20-mm-long graft groups. Pathway reinnervation
      was non-specific with a huge amount of motor fiber misdirection. A decrease in
      the number of misdirected motor fibers occurred with time and activity recovery.
      Muscle reinnervation was not specific with disturbance of the mosaic pattern and
      type-grouping formation. Preference of type I axons for reinnervating deeper
      zones was observed. Type I aberrant reinnervation was demonstrated in the muscle
      periphery. The mosaic distribution of type I and II muscle fibers was not stable,
      and readjustments were observed with time, correlating with grasping improvement.
      During grasping strength recovery, there was a decrease in the number of type I
      fibers peripherally located and an increase of those deeply disposed. A time- and
      activity-related recovery was associated with readjustment in the pathways and
      muscle fiber rearrangement. We suggest that muscle activity generates
      specificity.

PMID- 16279986
TI  - Ultrasound imaging of the rabbit peroneal nerve.
AB  - Ultrasound imaging of peripheral nerves is increasingly used in the clinic for a
      wide range of applications. Although yet unapplied for experimental neuroscience,
      it also has potential value in this research area. This study explores the
      feasibility, possibilities and limitations of this technique in rabbits, with
      special focus on peripheral nerve regeneration after trauma. The peroneal nerve
      of 25 New Zealand White rabbits was imaged at varying time intervals after a
      crush lesion. The ultrasonic appearance of the nerve was determined, and
      recordings were validated with in vivo anatomy. Nerve swelling at the lesion site
      was estimated from ultrasound images and compared with anatomical parameters. The
      peroneal nerve could reliably be identified in all animals, and its course and
      anatomical variations agreed perfectly with anatomy. Nerve diameters from
      ultrasound were related to in vivo diameters (p < 0.001, R(2) = 77%), although
      the prediction interval was rather wide. Nerve thickenings could be visualized
      and preliminary results indicate that ultrasound can differentiate between
      neuroma formation and external nerve thickening. The value of the technique for
      experimental neuroscience is discussed. We conclude that ultrasound imaging of
      the rabbit peroneal nerve is feasible and that it is a promising tool for
      different research areas within the field of experimental neuroscience.

PMID- 16279987
TI  - Large and small fiber neuropathy in chronic alcohol-dependent subjects.
AB  - The aim of the present study was to evaluate the occurrence of large and small
      fiber neuropathy among alcohol-dependent subjects and to correlate neuropathy
      with the pattern of alcohol abuse, age of the subjects, nutritional status, and
      biochemical parameters. The study sample comprised 98 consecutive alcohol
      dependent subjects without signs of malnutrition treated for detoxification
      voluntarily in the specialized unit of the Athens University Psychiatric Clinic
      in an inpatient basis. Polyneuropathy (PN) was graded using the neuropathy
      symptoms score and neurologic disability score, conduction velocity studies, and
      quantitative sensory tests. Seventy-seven men and 21 women aged 27-70 years took
      part in the study. PN was diagnosed in 57 subjects (58.2%). PN of both large and
      small fibers was found in 25 patients (25.5%); exclusively small fiber neuropathy
      was observed in 12 (12.2%) and exclusively large fiber neuropathy in 20 patients
      (20.4%). Neuropathy was significantly correlated with the age of the subjects,
      duration of alcohol abuse, liver dysfunction, macrocytosis, and blood sugar
      levels upon admission. PN was significantly more frequent in males than in
      females. The two groups of exclusively large and exclusively small fiber
      neuropathy did not differ significantly in any clinical and laboratory parameter.
      Subclinical neuropathy (stage 1) was observed in 11.2%, which also did not differ
      significantly in any clinical and laboratory parameter from the stage 2 PN group
      subjects. Our findings indicate the direct toxic effect of alcohol on peripheral
      nerve fibers as the main etiologic factor of alcoholic PN. Long-standing
      hyperglycemia may be another contributing factor. Impaired vitamin B(12)
      utilization may be also involved.

PMID- 16279988
TI  - Acute dysautonomia: a rare manifestation of diabetic autonomic neuropathy
      masquerading as pheochromocytoma.

PMID- 16279989
TI  - Chronic inflammatory demyelinating polyneuropathy after autologous peripheral
      blood stem cell transplantation.

PMID- 16279991
TI  - Charcot-Marie-Tooth disease due to the Thr124Met mutation in the myelin protein
      zero gene associated with multiple sclerosis.

PMID- 16279992
TI  - Peripheral nerve regeneration in cell adhesive peptide incorporated collagen
      tubes in rat sciatic nerve -- early and better functional regain.

PMID- 16279990
TI  - Multifocal motor neuropathy during treatment with infliximab.

PMID- 16279993
TI  - Isolated sural nerve neuropathies.

PMID- 16279994
TI  - Severe sensory neuropathy occurring in association with Hashimoto's thyroid
      disease.

PMID- 16279996
TI  - Could interchangeable use of dry powder inhalers affect patients?
AB  - The aim of asthma treatment is optimal disease control. Poor asthma control
      results in considerable patient morbidity, as well as contributing to the
      considerable burden placed by the disease on healthcare budgets. There is a need
      for costs to be carefully scrutinised, with the switching of patients to inhaler
      devices with lower acquisition costs likely to be increasingly considered.
      However, before such practice becomes widespread, it is important to establish
      whether or not this could adversely impact on patients and the level of disease
      control. For approval to have been given, all marketed inhalers must have
      satisfied current regulatory requirements for devices. Full preclinical and
      clinical development programmes are not required when application is made for
      authorisation to market a new inhaler containing an existing chemical entity,
      although clinical equivalence testing must be used. Both beneficial and adverse
      effects should be tested, and the limits of equivalence must be clearly defined,
      based on therapeutic relevance. It should be noted that equivalence studies are
      invalid when the end point is not responding (i.e. at the top of the dose
      response curve) and when equivalence limits approach or are equal to the
      magnitude of the drug effect. Approval on the basis of regulations designed to
      safeguard quality of dry powder inhalers does not mean that devices are
      interchangeable. When using an inhaler, there are many stages between the patient
      and the therapeutic effect, involving device design, pharmaceutical performance
      and patient behaviour. Regulations governing new devices cover only a few of the
      many factors affecting disease control. Furthermore, clinical trials to assess
      equivalence may not take into account factors in patient behaviour or variations
      in patient inhaler technique that may affect use of devices in real-life
      situations. When assessing the consequences of interchangeable use of dry powder
      inhalers on healthcare costs, it is important to ensure that the acquisition cost
      of the devices is not the only cost considered. Other costs that should be
      considered include the cost of time spent demonstrating to the patient how to use
      the new device, the cost of additional physician visits to address patient
      concerns and the management costs if disease control is adversely affected.

PMID- 16279997
TI  - Do all dry powder inhalers show the same pharmaceutical performance?
AB  - Important measures of pharmaceutical performance of dry powder inhalers include
      total emitted dose (TED, the quantity of drug emitted from the device when used
      at a fixed flow rate, typically 60 l/min or the flow rate achieved at a pressure
      drop of 4 kPa) and fine particle mass (FPM, the quantity of drug with small
      particles, typically with an aerodynamic diameter of less than 5 microns emitted
      from the device at a fixed flow rate). There is a wide range of dry powder
      inhalers available. The complexity of design decisions means that dry powder
      inhalers are very diverse, with identical designs unlikely. It is not surprising
      therefore that evidence from in vitro studies shows considerable variation in
      pharmaceutical performance of dry powder inhalers. Although neither TED nor FPM
      can accurately predict in vivo performance, it may be expected that highly
      variable or inhalation flow sensitive in vitro behaviour will be reflected in
      variable performance when used by patients.

PMID- 16279998
TI  - Can patients use all dry powder inhalers equally well?
AB  - If patients are unable to use their inhaler, drug delivery may be unsatisfactory
      and the patients may fail to benefit from the prescribed medication. It is
      important to consider whether patients can use all dry powder inhalers equally
      well. Changing a patient from a dry powder inhaler used well to one that the
      patient is unable to operate effectively could compromise asthma control. The
      many marketed dry powder inhalers reflect differences in design decisions that
      could affect lung deposition. Studies using different dry powder inhalers have
      confirmed that different lung deposition patterns are observed. Furthermore,
      there may be considerable individual variability in lung deposition. Differences
      in lung deposition patterns could have clinical effects. Studies may show similar
      clinical effectiveness with two inhalers, because most products are used at the
      plateau phase of the dose-response curve, although there may be differences in
      the adverse event profile. The ideal inhaler does not yet exist. Different dry
      powder inhalers show some but not all features of the ideal inhaler; hence,
      patients may prefer some aspects of one inhaler while favouring a different
      inhaler for other features. The individual balance of features will govern the
      overall preference for one inhaler over others. The method for operation of dry
      powder inhalers varies. Ease of use is seen as an important consideration when
      selecting an inhaler device, which should be evaluated in real-life studies using
      unselected patient populations. In conclusion, the evidence suggests that
      patients cannot use all dry powder inhalers equally well.

PMID- 16279999
TI  - Do patients show the same level of adherence with all dry powder inhalers?
AB  - Poor adherence with inhaled therapy presents a considerable problem. In the UK,
      non-adherence is estimated to occur in 10-46% of those prescribed inhaled
      corticosteroids and may contribute to an estimated 18-48% of asthma deaths.
      Before dry powder inhalers can be considered interchangeable, it is important to
      check that adherence is unaffected by any switching of the device dispensed to
      patients. Numerous studies have shown that adherence with inhaled medication is a
      multifactorial issue. A number of evidence-based guidelines have concluded that
      there is no difference in the delivery of treatments from different inhaler
      devices. However, many studies comparing different devices are designed to show
      equivalence. It is therefore difficult to determine whether the studies on which
      the guidelines are based were conducted with treatments already being used at the
      top of a dose-response curve. Furthermore, studies use selected patient
      populations who consent to take part and consequently receive regular contact
      with healthcare professionals, with emphasis on using the correct inhaler
      technique and on compliance. These studies do not therefore necessarily reflect
      real life. It is possible that patient preferences or perceptions of differences
      in efficacy are behind complaints when devices are switched. Patients vary in
      their preference for different dry powder inhalers, as shown in numerous studies
      of patient attitudes. There is evidence to indicate that patient claims of
      differences between inhalers that contain the same molecule from different
      manufacturers may have an objective basis. Healthcare professionals increasingly
      recognise the impact of patient attitudes on adherence. Accepting that patients
      make choices about their therapy is an integral part of achieving the partnership
      in management recommended by guidelines. The most effective treatment will not
      achieve disease control if it is not used or if it is used incorrectly. It may be
      short-sighted to change a device that a patient has chosen to one that is just
      given without consent, as this may result in poor adherence to therapy with
      consequent loss of control.

PMID- 16280000
TI  - Do healthcare professionals think that dry powder inhalers can be used
      interchangeably?
AB  - It is important to assess the attitudes of healthcare professionals to the
      interchangeable use of dry powder inhalers, as there is the potential for this to
      occur more frequently in the future. A survey of healthcare professionals in the
      UK found that 87% were concerned about potential problems arising from
      prescriptions that do not specify the device to be dispensed, and 46% were aware
      of actual incidents in which patients received an unfamiliar inhaler, including
      patient confusion, ineffective inhaler technique and the need to reissue
      prescriptions. In another survey conducted among 427 primary and secondary care
      physicians in Germany, Netherlands, UK and USA, one third of the physicians
      considered the device before considering the chemical entity within a class of
      treatments and over half the respondents reported problems with the device as one
      of the main reasons for switching inhaled therapy. In a survey conducted in
      Australia, Canada, France, Germany and UK, over 90% of the 726 physicians
      interviewed thought that interchangeable use of dry powder inhalers would have a
      negative impact on patient compliance and device handling and on willingness to
      use the inhaler if the patient was not involved in the choice. In total, 79% of
      physicians thought that substitution of a patient's regular dry powder inhaler
      with another could have a negative impact on asthma control. The majority of
      physicians (95%) were opposed to substitution of one dry powder inhaler for
      another if the pharmacist does not consult the patient or physician. A majority
      (86%) were concerned that switching between dry powder inhalers would have an
      adverse impact on workload. Only 9% of physicians thought that dry powder
      inhalers were interchangeable, with almost eight out of 10 (79%) considering that
      there should be official recognition that they are not interchangeable. In
      conclusion, a number of surveys among healthcare professionals have shown that
      they believe patient involvement in treatment choice to be essential for
      adherence to therapy. Dry powder inhalers were perceived as different and not
      interchangeable, with physicians opposed to substitution of one dry powder
      inhaler by another without consultation with the patient or physician.
      Consequently, physicians are in favour of official recognition that dry powder
      inhalers are not interchangeable, with any cost benefits likely to be outweighed
      by the need for additional consultations and prescriptions.

PMID- 16280001
TI  - Do patients think that dry powder inhalers can be used interchangeably?
AB  - As recognised in management guidelines, patients are the most important group of
      people in any prescribing decision. Despite their importance, few studies have
      asked what patients think about being switched between different inhalers. This
      paper reports two such studies, one involving interviews of a sample of patients
      and the other consisting of a quantitative survey of patients across five
      countries. In the qualitative study, four of the five patients interviewed
      reported that they would be confused, worried and unhappy about a switch in their
      dry powder inhaler and would revisit their physician to be shown how to use the
      inhaler or to ask for a new prescription for their old inhaler. In the
      quantitative survey of 499 patients with asthma, more than half (51%) were
      opposed to their current dry powder inhaler being replaced by a substitute
      device, with 83% reporting concerns. There was considerable concern about
      training in use of the new device and confusion about the need for change. Almost
      a quarter of patients (23%) would want training, and 23% of patients thought they
      would need information about the new inhaler. From limited information, it
      appears that patients would be concerned about switching of their existing dry
      powder inhaler for another, with the potential for confusion, need for additional
      consultations and need for training in the new device.

PMID- 16280002
TI  - Are outcomes the same with all dry powder inhalers?
AB  - Most clinicians and patients would intuitively say that the inhaler device used
      influences the outcome achieved in asthma. However, it is important to have
      objective evidence to support or refute this view. Systematic reviews have
      suggested that there is no difference in clinical effectiveness between dry
      powder inhalers and metered-dose inhalers. However, the studies included in the
      review were randomised clinical trials and not studies based on real-life
      clinical practice. In the real world, the efficacy of products as determined in a
      specified and well-monitored population is only one aspect of product performance
      -patient characteristics and behaviour are critical. Observational studies in
      real-world primary care settings suggest that the choice of inhaler device has an
      important impact on asthma outcomes. The IMS Mediplus database has now been used
      to compare outcomes among patients receiving initial maintenance therapy with
      beclometasone dipropionate administered via different dry powder inhalers.
      Patients using the DISKHALER dry powder inhaler used significantly less short
      acting beta(2)-agonist than those using the ROTAHALER dry powder inhaler. This
      suggests a difference in the level of asthma control with the different devices,
      even when the same chemical entity is delivered. Real-world studies suggest,
      therefore, that outcomes are not always the same with all dry powder inhalers.
      This indicates the need for further studies to investigate the impact of inhaler
      device choice and the impact of switching between devices.

PMID- 16280003
TI  - The way forward: dry powder inhalers should only be switched with physician
      agreement and patient training.
AB  - Assessment of pharmaceutical performance, patient behaviour and clinical outcomes
      shows that dry powder inhalers cannot be used interchangeably, even if they
      contain the same active chemical entity. Consequently, there should be no
      switching of device without the involvement of the physician and appropriate
      training for the patient.

PMID- 16280004
TI  - Editorial: It's good to talk.

PMID- 16280005
TI  - Melanocortin-1 receptor structure and functional regulation.
AB  - The melanogenic actions of the melanocortins are mediated by the melanocortin-1
      receptor (MC1R). MC1R is a member of the G-protein-coupled receptors (GPCR)
      superfamily expressed in cutaneous and hair follicle melanocytes. Activation of
      MC1R by adrenocorticotrophin or alpha-melanocyte stimulating hormone is
      positively coupled to the cAMP signaling pathway and leads to a stimulation of
      melanogenesis and a switch from the synthesis of pheomelanins to the production
      of eumelanic pigments. The functional behavior of the MC1R agrees with emerging
      concepts in GPCR signaling including dimerization, coupling to more than one
      signaling pathway and a high agonist-independent constitutive activity accounting
      for inverse agonism phenomena. In addition, MC1R displays unique properties such
      as an unusually high number of natural variants often associated with clearly
      visible phenotypes and the occurrence of endogenous peptide antagonists.
      Therefore MC1R is an ideal model to study GPCR function. Here we review our
      current knowledge of MC1R structure and function, with emphasis on information
      gathered from the analysis of natural variants. We also discuss recent data on
      the regulation of MC1R function by paracrine and endocrine factors and by
      external stimuli such as ultraviolet light.

PMID- 16280006
TI  - Melanoma inhibitory activity (MIA): an important molecule in melanoma development
      and progression.
AB  - Cutaneous malignant melanoma is the leading cause of skin cancer death in
      industrialized countries. Melanoma development and progression are well defined
      by clinical and histopathological aspects; however, detailed analysis of
      molecular changes is still ongoing. The protein MIA, which is strongly expressed
      in melanoma cells but not in melanocytes, is likely to represent a key molecule
      regulating melanoma progression. Consistent with this, several in vitro and in
      vivo model systems indicate a direct involvement of MIA in melanoma migration and
      invasion, with recent studies suggesting a central role for MIA in early melanoma
      development by regulating important melanoma-related pathways and molecules. The
      latest developments in MIA research are summarized in this review, which
      describes recently published data related to the MIA protein structure and
      function, the role of MIA in melanoma development and progression, and the
      regulation of MIA expression. Furthermore, newly discovered MIA-homologous genes
      are discussed.

PMID- 16280008
TI  - Pax3 target gene recognition occurs through distinct modes that are
      differentially affected by disease-associated mutations.
AB  - The paired box protein Pax3 is an essential regulator of muscle and neural crest
      derived cell types, including melanocytes. Within this lineage, Pax3 has been
      shown to regulate the genes encoding microphthalmia-associated transcription
      factor (Mitf) and tyrosinase-related protein-1 (Trp-1), despite each having
      dissimilar Pax3 recognition sequences. We have, therefore, examined the
      structural requirements for Pax3 binding to the MITF and TRP-1 promoter elements,
      focusing on the contribution of the paired domain and homeodomain to Pax3 target
      site recognition. Unexpectedly, although the MITF element is characterized by
      suboptimal recognition motifs for the paired domain and homeodomain, it sustains
      a higher level of Pax3 binding than TRP-1, which contains a canonical paired
      domain site. The basis for this difference involves a context-dependent
      cooperative binding event requiring both the paired domain and homeodomain, while
      the paired domain alone is sufficient for TRP-1 recognition. Significantly, the
      analysis of Waardenburg syndrome mutations reveals marked disparity in their
      effects on MITF and TRP-1 binding that further underscores mechanistic
      differences in their interaction with Pax3. Importantly, these mutations also
      exert distinct effects on the ability of Pax3 to regulate reporter genes fused to
      either the MITF or TRP-1 promoters. Our results, therefore, establish that Pax3
      can regulate target genes through alternate modes of DNA recognition that are
      differentially impacted by disease-causing mutations, which together have
      important implications for understanding Pax3-regulated gene networks.

PMID- 16280007
TI  - Membranous complexes characteristic of melanocytes derived from patients with
      Hermansky-Pudlak syndrome type 1 are macroautophagosomal entities of the
      lysosomal compartment.
AB  - Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder resulting from
      mutations in a family of genes required for efficient transport of lysosomal
      related proteins from the trans-Golgi network to a target organelle. To date,
      there are several genetically distinct forms of HPS. Many forms of HPS exhibit
      aberrant trafficking of melanosome-targeted proteins resulting in incomplete
      melanosome biogenesis responsible for oculocutaneous albinism observed in
      patients. In HPS-1, melanosome-targeted proteins are localized to characteristic
      membranous complexes, which have morphologic similarities to macroautophagosomes.
      In this report, we evaluated the hypothesis that HPS-1-specific membranous
      complexes comprise a component of the lysosomal compartment of melanocytes. Using
      indirect immunofluorescence, an increase in co-localization of misrouted
      tyrosinase with cathepsin-L, a lysosomal cysteine protease, occurred in HPS-1
      melanocytes. In addition, ribophorin II, an integral endoplasmic reticulum
      protein that is also a component of macroautophagosomes, and LC3, a specific
      marker of macrophagosomes, demonstrated localization to membranous complexes in
      HPS-1 melanocytes. At the electron microscopic level, the membranous complexes
      exhibited acid phosphatase activity and localization of exogenously supplied
      horseradish peroxidase (HRP)-conjugated gold particles, indicating incorporation
      of lysosomal and endosomal components to membranous complexes, respectively.
      These results confirm that membranous complexes of HPS-1 melanocytes are
      macroautophagosomal representatives of the lysosomal compartment.

PMID- 16280009
TI  - Inhibition of skin pigmentation by an extract of Lepidium apetalum and its
      possible implication in IL-6 mediated signaling.
AB  - The development of effective skin-lightening agents is an increasingly important
      area of research aimed at the treatment of hyperpigmentation induced by UV
      irradiation or by medical conditions such as melasma, postinflammatory
      melanoderma and solar lentigo. Although some inhibit tyrosinase, identifying and
      understanding the mechanisms of action of other agents is an important goal if
      more effective pigmentation inhibitors are to be developed. We present here that
      an extract of Lepidium apetalum (ELA) decreased UV-induced skin pigmentation in
      brown guinea pigs and melanogenesis of HM3KO human melanoma cells. Interestingly,
      ELA did not reduce melanogenesis in HM3KO cells unless they were co-cultivated in
      keratinocyte-conditioned medium prepared by culturing keratinocytes with ELA.
      Under these conditions, ELA decreased tyrosinase mRNA and protein expression as
      well as melanin content via an ELA-mediated increase in keratinocyte IL-6
      production which in turn was shown to decrease in the expression Mitf, a
      transcription factor implicated in tyrosinase gene expression and melanocyte
      differentiation. The results reveal that ELA may be an effective inhibitor of
      hyperpigmentation caused by UV irradiation or by pigmented skin disorders through
      a mechanism involving IL-6-mediated downregulation of Mitf rather than a direct
      inhibition of tyrosinase activity.

PMID- 16280010
TI  - Triazine-based tyrosinase inhibitors identified by chemical genetic screening.
AB  - As most of the available depigmenting agents exhibit only modest activity and
      some exhibit toxicities that lead to adverse side effects after long-term usage,
      there remains a need for novel depigmenting agents. Chemical genetic screening
      was performed on cultured melanocytes to identify novel depigmenting compounds.
      By screening a tagged-triazine library, we identified four compounds, TGH11,
      TGD10, TGD39 and TGJ29, as potent pigmentation inhibitors with IC50 values in the
      range of 10 microM. These newly identified depigmenting compounds were found to
      function as reversible inhibitors of tyrosinase, the key enzyme involved in
      melanin synthesis. Tyrosinase was further confirmed as the cellular target of
      these compounds by affinity chromatography. Kinetic data suggest that all four
      compounds act as competitive inhibitors of tyrosinase, most likely competing with
      L-3,4-dihydroxyphenylalanine (L-DOPA) for binding to the DOPA-binding site of the
      enzyme. No effect on levels of tyrosinase protein, processing or trafficking was
      observed upon treatment of melanocytes with these compounds. Cytotoxicity was not
      observed with these compounds at concentrations up to 20 muM. Our data suggest
      that TGH11, TGD10, TGD39 and TGJ29 are novel potent tyrosinase inhibitors with
      potential beneficial effects in the treatment of cutaneous hyperpigmentation.

PMID- 16280011
TI  - Melanin in human irides of different color and age of donors.
AB  - Melanin is the main chromophore of the human iris. This pigment is considered to
      be the most important factor that determines the color of the irides. Previous
      studies based mainly on chemical degradation methods showed that brown irides
      contain more melanin than blue ones. In our study, we used electron spin
      resonance (ESR) spectroscopy to detect and characterize melanin free radical
      centers and associated iron in human irides. Based on this method, we determined
      the amount of melanin in the irides and the relative content of iron in iridial
      melanin as a function of their color, shade, and the age of their donors.
      Chemical degradation of iridial homogenates enabled us to characterize the
      structure of eumelanin and determine the content of pheomelanin present in human
      and bovine irides. The ESR amplitude, the normalized intensity obtained by double
      integration of the ESR signal of melanin, and the content of the pigment in the
      irides depended on color and shade of the eyes being 40% higher in the brown
      group of the irides compared with all other groups. On the other hand, the
      relative iron content normalized to the melanin content in light blue irides
      showed a small decrease with age of donors. Melanin in human and bovine irides
      was mostly composed of eumelanin, and pheomelanin content was of the order of a
      few percent. Although some differences in the structure of eumelanin present in
      the human and bovine irides are possible, the results obtained in this study
      suggest that human irides contain eumelanin with very similar chemical
      properties.

PMID- 16280013
TI  - The histological analysis, colorimetric evaluation, and chemical quantification
      of melanin content in 'suntanned' fish.
AB  - Human melanocytes respond to UV irradiation by increasing the synthesis of
      melanin. While much is now understood of the pathways governing this process and
      the nature of the melanin synthesized, little is known of melanins produced by
      lower vertebrates and their capacity to respond to UV. Here we report that a
      fish, red seabream, can undergo 'suntanning'. Histological, colorimetric and
      chemical assays were performed for suntanned red seabream fish bred in net cages
      to analyse the melanins and compared with shaded or wild red seabream fish. For
      color evaluation, the L* values of suntanned fish were dramatically lower than
      those in the other two groups. Pyrrole-2,3,5-tricarboxylic acid (PTCA), an
      indicator of eumelanin, was detected in suntanned fish at five times higher
      levels than in shaded or wild fish while 4-amino-3-hydroxyphenyl-alanine (4-AHP),
      a marker for pheomelanin, could not be detected in any of the samples.
      Histological analysis showed that melanocytes in the suntanned skin enlarged and
      increased in number to form a monolayer at the surface of the skin. Analysis of
      L* values and PTCA levels showed quite a high correlation coefficient (r = 
      0.843). When comparing shaded and wild red seabream fish, the scores were closer
      but some significant differences were still found in some body areas. These
      results indicate that eumelanin accumulates in suntanned fish during the increase
      in skin color, which is induced by sunlight, presumably by ultraviolet radiation.

PMID- 16280015
TI  - The role of stress in ageing: research on the nematode, Caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans has proven a robust genetic model for studies
      of aging and the roles of stress. In this review we focus on the genetics of
      select long-lived and short-lived mutants of C. elegans that have proven useful
      in revealing the relationships that exist between oxidative stress and life span.
      The former are known to be controlled by an insulin/insulin-like signaling
      pathway, while the latter are affected by mitochondrial functions.

PMID- 16280016
TI  - Functional changes induced by chronic UVA irradiation to cultured human dermal
      fibroblasts.
AB  - Ultraviolet (UV) irradiation induces damage of the skin, and in particular,
      photoageing is known to be the result of chronic UV irradiation. Many
      investigations have attempted to clarify the mechanisms of photoageing induced by
      chronic UVA irradiation, but consensus has not been achieved yet by in vivo
      experiments, mostly due to differences among UV sources and animals used for
      experiments. In vitro experiments have shown that a single exposure to UVA
      irradiation causes overexpression of matrix metalloproteinases and denaturation
      of collagen, but the mechanisms of the photoageing effects of chronic UVA
      irradiation are still unclear. To examine the effects of chronic UVA irradiation,
      we used an in vitro fibroblast cellular ageing system as a model of photoageing.
      Chronic UVA irradiation of normal human fibroblasts induced shortening of the
      cellular life span and an increase of cellular diameter, in parallel with
      expression of senescence-associated beta-galactosidase. Extracellular degradation
      enzyme, matrix metalloproteinase 1 (MMP-1) was overexpressed after repeated UVA
      irradiation, but tissue inhibitor of metalloproteinase 1 (TIMP-1) expression was
      hardly changed by chronic UVA irradiation. We conclude that chronic UVA
      irradiation of normal human fibroblasts induces cellular functional changes,
      leading to accelerated cellular ageing and MMP-1 overexpression.

PMID- 16280017
TI  - Characteristic alterations of cutaneous neurogenic factors in photoaged skin.
AB  - BACKGROUND: Although it has been recognized that photoageing and chronological
      ageing differ in various morphological and biological aspects, the characteristic
      alterations of cutaneous neurogenic factors in photoaged skin are poorly
      characterized. OBJECTIVES: To characterize cutaneous neurogenic factors,
      including innervation, neuropeptides, nerve growth factor and interactions of
      mast cells, in photoaged skin. SUBJECTS AND METHODS: Paired biopsy specimens were
      obtained from sun-exposed volar forearm skin and from sun-protected dorsal upper
      arm skin of 20 elderly subjects. Various cutaneous neurogenic factors, including
      innervation, neuropeptides, neurokinin receptor, nerve growth factor, neurogenic
      inflammation and morphology of mast cells, were compared in sun-exposed vs. sun
      protected skin quantitatively and qualitatively. RESULTS: Cutaneous neurogenic
      factors associated with photoageing were characterized by a significant increase
      in the densities of dermal and intraepidermal nerve fibres, a correlation between
      epidermal innervation and the severity of photodamage, increases in the number of
      neuropeptidergic sensory nerve fibres in the dermis and in tissue levels of
      sensory neuropeptides, increases in the content of nerve growth factor, reduced
      expression of neurokinin receptor 1 by epidermal keratinocytes and by vascular
      endothelial cells and a tachykinin-specific reduction of cutaneous neurogenic
      inflammation. Mast cells in photodamaged skin showed several characteristic
      morphological features, including various degrees of activation and an intimate
      association with fibroblasts, which were distinct from those in sun-protected
      skin. Furthermore, mast cells in photodamaged skin possessed larger amounts of
      substance P within their granules than did those in sun-protected skin.
      CONCLUSIONS: These findings document for the first time characteristic
      alterations of cutaneous neurogenic factors in photodamaged skin and suggest that
      the cutaneous nervous system may be involved in photoageing processes.

PMID- 16280018
TI  - Correlation between age and the secretions of melanocyte-stimulating cytokines in
      cultured keratinocytes and fibroblasts.
AB  - BACKGROUND: The majority of skin changes associated with ageing are caused by
      photoageing and reflect cumulative sun exposure. Although the actinic damage
      plays a major role in skin pigmentation, it is also important to examine the
      effects of chronological cellular ageing on the pigmentation. The chief cellular
      components of the skin other than melanocytes are keratinocytes and fibroblasts,
      and the influences of age-related changes in those cells on skin pigmentation
      have not been elucidated. OBJECTIVE: To clarify the effects of cellular ageing of
      keratinocytes and fibroblasts on age-related skin pigmentation. METHODS: Using
      ELISA analysis, we measured the level of melanogenic cytokines secreted by
      cultured keratinocytes and fibroblasts derived from skin of various chronological
      ages. We also compared the cytokine secretion by cultured keratinocytes between
      the second and fifth cultures. RESULTS: There was no correlation between age and
      hepatocyte growth factor (HGF), stem cell factor (SCF), and basic fibroblast
      growth factor (bFGF) secretion by fibroblasts. On the other hand, a significant
      positive correlation existed between age and interleukin ((IL)-1alpha secretion
      (R2=0.50, P=0.002), and a relatively weak correlation existed between age and
      endothelin-1 (ET-1) secretion (R2=0.17, P=0.051, not significant). The IL-1alpha
      secretion by keratinocytes was significantly increased in the fifth cultures
      compared with the second cultures (P<0.005). CONCLUSIONS: These findings suggest
      that IL-1alpha secretion increases as cells grow older, and the increased
      secretion of IL-1alpha by aged keratinocytes may stimulate HGF production in
      dermal fibroblasts paracrinely and ET-1 production in keratinocytes autocrinely,
      which stimulates melanocyte proliferation and induces an increase of tyrosinase
      activity in melanocytes. Because IL-1alpha is a primary mediator that responds to
      inflammation and injury, the transcription of genes involved in skin inflammation
      may be persistently induced in the aged skin. Thus the increased secretion of IL
      1alpha by aged keratinocytes in the aged skin may play a role in the accentuated
      cutaneous pigmentation and other skin ageing.

PMID- 16280019
TI  - N-retinoyl-D-glucosamine, a new retinoic acid agonist, mediates topical retinoid
      efficacy with no irritation on photoaged skin.
AB  - BACKGROUND: Chronic ultraviolet (UV) radiation from sunlight induces wrinkle
      formation. Retinoic acid (RA) can markedly improve wrinkles, although RA does
      have some side-effects, such as skin irritation. As the efficacy and cytotoxicity
      of RA has been traced to its free carboxylic acid, we synthesized a new molecule,
      N-retinoyl-D-glucosamine (GRA), in which a glucosamine has been attached to the
      polar end group of all-trans retinoic acid. OBJECTIVES: To analyse the effect of
      topical GRA in wrinkle repair and anti-irritation in photoaged mice compared with
      topical RA, as well as to determine retinoic acid receptor (RAR) and retinoid X
      receptor (RXR) transactivation activity in vitro. METHODS: Hairless mice were
      irradiated with 60 mJ cm-2 of UVB for 10 weeks, and then topically treated with
      0.05% GRA or 0.05% RA for 8 weeks. An in vitro transcriptional assay was
      performed and the activity of GRA in 293 cells transfected with RAR-alpha or RXR
      alpha expression plasmid and luciferase reporter plasmid then determined.
      RESULTS: Topical GRA and RA brought about almost complete disappearance of the
      wrinkles caused by UVB irradiation. The two ligands promoted both a wide repair
      zone histologically, and the expression of type 1 collagen in the skin. In
      contrast, topical GRA treatment did not produce irritation such as erythema or
      roughness, or alteration of transepidermal water loss values, compared with RA.
      In the in vitro luciferase assay, GRA resulted in significant dose-dependent RAR
      transactivation activity in a 100 times higher concentration range than RA. GRA
      did not mediate RXR transactivation activity at all. CONCLUSIONS: Topical GRA
      appears to be able to repair photoaged skin damage without any of the irritation
      caused by topical RA, probably via RAR transactivation activity.

PMID- 16280020
TI  - Protective effect of matrix metalloproteinase inhibitors against epidermal
      basement membrane damage: skin equivalents partially mimic photoageing process.
AB  - BACKGROUND: The epidermal basement membrane (BM) plays important roles in
      adhesion between epidermis and dermis, and in controlling epidermal
      differentiation. The BM has been reported to be damaged in sun-exposed skin.
      Although matrix metalloproteinases (MMPs) are believed to be involved in the BM
      damage, there is no good in vitro model for examining BM damage by MMPs or for
      exploring methods to protect the BM. OBJECTIVES: To examine the involvement of
      MMPs in BM damage and approaches to protect the BM from such damage by using an
      in vitro skin-equivalent (SE) model. METHOD: SE was prepared by culturing human
      keratinocytes on contracted collagen gel including human fibroblasts. MMP-1, -2, 
      3 and -9, laminin 5 and type IV and VII collagens were determined by specific
      sandwich ELISAs, and MMP-2 and MMP-9 were analysed by gelatin zymography.
      Histological examination of SE was also carried out. RESULTS: Despite production
      of BM components such as laminin 5 and type IV and VII collagens in SEs, BM was
      rarely observed at the dermal-epidermal junction. Several MMPs, such as MMP-1, 
      2, -3 and -9, were observed to be present in conditioned media and some of them
      were in active forms. Tissue inhibitor of metalloproteinase (TIMP)-2 was not
      detected, although TIMP-1 was present. Synthetic MMP inhibitors, CGS27023A and
      MMP-inhibitor I, which inhibit MMP-1, -2, -3 and -9, markedly augmented
      deposition of laminin 5 and type IV and VII collagens at the dermal-epidermal
      junction, resulting in the formation of continuous epidermal BM. CONCLUSIONS: Our
      results indicate that MMPs are involved in the degradation of BM in SEs, and that
      MMP inhibitors exert a protective effect against BM damage.

PMID- 16280021
TI  - Enhancement of ultraviolet-induced apoptosis by NF-kappaB decoy oligonucleotides.
AB  - BACKGROUND: A decoy strategy utilizing oligonucleotides (ODN) containing the
      specific binding sequence of a certain transcription factor has been developed
      and is considered to be a potential new class of antigene therapy. However, the
      application of this new therapeutic modality to skin diseases has not been fully
      documented. OBJECTIVES: The aim of this work was to examine the effects of the
      nuclear factor (NF)-kappaB decoy ODN on UV-elicited skin change. METHODS: Mouse
      keratinocyte Pam 212 cells were transfected with NF-kappaB decoy ODN to examine
      the effects of the decoy ODN on ultraviolet (UV) B-induced apoptosis. Tape
      stripped rat dorsal skin was treated with an ointment containing NF-kappaB decoy
      ODN for the examination of the in vivo impact of the decoy ODN on sunburned cell
      (SBC) formation and UVB erythema. RESULTS: NF-kappaB decoy ODN specifically
      induced apoptosis of Pam 212 cells and SBC formation was significantly enhanced
      by topical NF-kappaB decoy ODN ointment, while UV-induced erythema was not
      affected. CONCLUSIONS: These data suggest that enhancement of UV-induced
      apoptosis by NF-kappaB decoy ODN may play a cancer-preventive role by further
      eliminating photodamaged keratinocytes.

PMID- 16280022
TI  - Impaired removal of 8-hydroxydeoxyguanosine induced by UVB radiation in naevoid
      basal cell carcinoma syndrome cells.
AB  - BACKGROUND: The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal
      dominant disorder characterized by tumorigenesis such as multiple basal cell
      carcinomas, odontogenic keratocysts and developmental abnormalities such as
      calcified dural folds and rib-anomalies. Recently, it has been shown that
      ultraviolet (UV) B exposure produced more BCCs in ptch knockout mice than wild
      mice. OBJECTIVES: To Investigate the role of UV in development of BCCs in NBCCS,
      cellular sensitivity to killing by UVB and removal of UVB-induced oxidative DNA
      damage were examined using fibroblasts derived from patients with NBCCS under
      physiologically relevant doses of UVB exposure. PATIENTS AND METHODS: Three
      patients with NBCCS, a 59-year-old male patient, an 18-year-old boy and a 13-year
      old boy were examined by photobiological analysis. Cellular sensitivity to
      killing by UVB and UVC and removal of oxidative DNA damage caused by UVB were
      tested using fibroblasts derived from these patients. We measured cellular 8
      hydroxydeoxyguanosine (8-OHdG) after UVB exposure up to 24 h after UVB exposure
      using high-performance liquid chromatography. RESULTS: All three cell strains
      derived from the patients with NBCCS were hypersensitive to killing by UVB (D10:
      50-70% of normal) but not by UVC. After UVB exposure, the production of 8-OHdG
      increased dose dependently up to 3200 J m-2 in both NBCCS cells and normal cells.
      In normal cells, 8-OHdG after UVB exposure returned to its basal level during 24
      h, whereas in NBCCS cells the amount of 8-OHdG after 800 J m-2 of UVB exposure
      did not return to its basal level even after 24 h. The result indicates the
      removal of 8-OHdG could be impaired in NBCCS cells. Ability in removal of thymine
      dimers of NBCCS cells was similar to that of normal cells. CONCLUSIONS:
      Hypersensitivity to UVB can be one of the diagnostic tools of NBCCS for those
      whose clinical features have not yet completed. Hypersensitivity to cell killing
      and the impairment of removal of 8-OHdG after UVB exposure may play some role in
      developing BCCs and other tumours in NBCCS.

PMID- 16280023
TI  - Cutaneous immunological activation elicited by a low-fluence pulsed dye laser.
AB  - BACKGROUND: Three years ago, the nonablative wrinkle reduction laser (a 585-nm
      laser, Chromogenex V3; Chromogenex Light Technologies, Llanelli, U.K.) was
      developed, and there have already been several reports about its clinical
      effectiveness. The Chromogenex V3 laser has also been reported to be effective in
      treating acne and atopic dermatitis. These results suggest that the Chromogenex
      V3 laser has some immunological role. In this study, we investigated
      immunological changes elicited by laser irradiation at the ultrastructural level
      and by analysis of interleukin (IL)-2 and IL-4 mRNA in skin homing T lymphocytes.
      MATERIALS AND METHODS: Eight healthy adult volunteers (mean age 56.3 years, range
      25-66 years) were recruited for this study. Ultrastructural analysis was done 3 h
      after the laser irradiation, as well as 1 day, 3 days, 1 week, 2 weeks, 4 weeks
      and 5 weeks later. IL-2 and IL-4 mRNAs in skin homing T cells cultured for 6
      weeks were semiquantitatively measured using reverse transcriptase-polymerase
      chain reaction. RESULTS: Ultrastructural observations revealed that at 3 h after
      laser therapy, neutrophils, monocytes and mast cells could already be seen in the
      extravascular dermis. These dermal acute inflammatory changes were observed also
      at 1 week after laser treatment. Two weeks after laser treatment, the capillaries
      showed an almost normal structure. Four weeks after laser treatment, many
      lymphocytes and fibroblasts were observed. The numbers of these lymphocytes
      increased further at 5 weeks after the laser treatment. One week after the laser
      irradiation, all subjects were positive for IL-2 mRNA and for IL-4 mRNA. The
      level of IL-4 mRNA was larger compared with that of IL-2 mRNA in all subjects.
      CONCLUSION: The Chromogenex V3 is a 585-nm visible light laser, and it may affect
      the skin not only by selective photothermolysis but also by direct cutaneous
      immunological activation.

PMID- 16280024
TI  - Islet-1 expression and its colocalization with luteinising hormone, thyroid
      stimulating hormone and oestrogen receptor alpha in the developing pituitary
      gland of the sheep foetus.
AB  - Islet-1 has been reported to be involved in pituitary development in the early
      stages of mouse embryogenesis. Oestrogen receptor (ER) and its expression may be
      involved in regulating pituitary development and its hormone-secreting function.
      Islet-1 expression and its correlations to ER in the developing pituitary gland
      are unknown. We therefore determined the pituitary cell specific expression of
      Islet-1 and its colocalization with ER alpha (ERalpha) in sheep foetus by
      immunohistochemistry. The results demonstrated that Islet-1-immunoreactive (ir)
      cells were distributed throughout the pituitary gland from day 60 of gestation
      until birth. The Islet-1-ir cell number was significant higher at day 90 and 120
      of gestation compared to that at day 60 and at birth. All of the ERalpha-ir cells
      were colocalized with Islet-1 at day 60 of gestation, although a few ERalpha-ir
      cells were negative for Islet-1 in the later stage of gestation. The dominant
      cell type expressing Islet-1 is the gonadotroph, although small proportions of
      thyrotrophs and lactotrophs also express Islet-1. The proportion of luteinising
      hormone-ir gonadotrophs possessing Islet-1 kept rising from day 60 to day 120 of
      gestation and persisted until birth. The proportion of thyroid-stimulating
      hormone-ir cells expressing Islet-1 was at a high level from day 60-120 of the
      gestation and significantly declined at birth. The percentage of prolactin (PRL)
      ir cells expressing Islet-1 was about 20% at day 60 of gestation. Very few PRL-ir
      cells contained Islet-1 in later stages of gestation. These data suggest that the
      development and functional establishment of pituitary gonadotrophs, thyrotrophs
      and lactotrophs might be regulated by the expressions of Islet-1 and ERalpha and
      by their interactions, although any mechanisms need to be elucidated further.

PMID- 16280025
TI  - Glucocorticoids and the development of agonistic behaviour during puberty in male
      golden hamsters.
AB  - During puberty, the agonistic behaviour of male golden hamsters undergoes a
      transition from play fighting to adult aggression. Repeated exposure to social
      stress early in puberty accelerates this transition. The present study
      investigated the possible role of glucocorticoids on the maturation of agonistic
      behaviour. First, we compared serum cortisol levels following a 20-min restraint
      stress during early puberty, mid-puberty or adulthood. Across puberty, animals
      exhibited a two-fold increase in post-restraint cortisol levels. We also compared
      corticotrophin-releasing hormone (CRH) immunoreactive fibres projecting to the
      median eminence between animals in early puberty and adulthood. The CRH fibre
      density was two-fold greater in adults compared to juveniles. Furthermore, we
      investigated the effects of stress hormones on the maturation of agonistic
      behaviour. Male hamsters were injected daily with dexamethasone, a corticosteroid
      receptor type II agonist (0, 10 or 40 microg/100 g), early in puberty from
      postnatal day 31 (P-31) to P-36. When paired with a smaller and younger intruder
      on P-37, attack frequency did not differ between groups. However, dexamethasone
      treated animals showed a dose-dependent decrease in the percentage of play
      fighting attacks and an increase in the percentage of adult attacks. In summary,
      puberty can be described as a period of increasing hypothalamic-pituitary-adrenal
      activity in male golden hamsters. Moreover, increasing glucocorticoid levels
      influence the maturation of agonistic behaviour. These data shed new light on the
      neuroendocrine mechanisms that regulate the maturation of social behaviours
      during puberty.

PMID- 16280026
TI  - Modelling the hypothalamic control of growth hormone secretion.
AB  - Here, we construct a mathematical model of the hypothalamic systems that control
      the secretion of growth hormone (GH). The work extends a recent model of the
      pituitary GH system, adding representations of the hypothalamic GH-releasing
      hormone (GHRH) and somatostatin neurones, each modelled as a single synchronised
      unit. An unpatterned stochastic input drives the GHRH neurones generating pulses
      of GHRH release that trigger GH pulses. Delayed feedback from GH results in
      increased somatostatin release, which inhibits both GH secretion and GHRH
      release, producing an overall pattern of 3-h pulses of GH secretion that is very
      similar to the secretory profile observed in male rats. Rather than directly
      stimulating somatostatin release, GH feedback triggers a priming effect,
      increasing releasable stores of somatostatin. Varying this priming effect to
      reduce the effect of GH can reproduce the less pulsatile form of GH release
      observed in the female rat. The model behaviour is tested by comparison with
      experimental observations with a range of different experimental protocols
      involving GHRH injections and somatostatin and GH infusion.

PMID- 16280027
TI  - Role of sex and sex steroids in mediating pituitary-adrenal responses to acute
      buspirone treatment in sheep.
AB  - Systematic characterisation of sex differences in the serotonergic modulation of
      the hypothalamic-pituitary-adrenal (HPA) axis may assist with our understanding
      of why stress-related disorders are disproportionately represented in women. In
      this study, we examined the acute effects of buspirone, a serotonergic 1A
      receptor subtype agonist, on the endocrine endpoints of adrenocorticotrophin
      (ACTH) and cortisol secretion in gonadectomised male and female sheep. Each sheep
      was treated with an acute i.v. injection containing vehicle or buspirone (0.03,
      0.1 and 0.3 mg/kg) in the presence and absence of sex steroid replacement (SSR).
      In males, SSR treatment consisted of testosterone (2 x 200 mg s.c. pellets) and,
      in females, the mid-luteal phase of the oestrus cycle was simulated by treatment
      with oestradiol (1 cm s.c. implant) and an intravaginal controlled internal drug
      release device containing 0.3 g progesterone. ACTH, cortisol, testosterone and
      progesterone were measured in jugular blood. Basal ACTH levels were higher in
      males, whereas basal cortisol levels were higher in females, regardless of sex
      steroid status. The magnitude of the increase in ACTH and cortisol secretion
      following buspirone treatment was dose-dependent. There were no differences in
      the ACTH responses of males and females to buspirone treatment, either in the
      presence or absence of sex steroid replacement. However, although the cortisol
      response to buspirone was greater in females, there was no discernable effect of
      sex steroid status in addition to this sex difference on either basal or
      buspirone-stimulated cortisol release. We conclude that the larger basal and
      buspirone-stimulated cortisol response measured in females may reflect a sex
      difference, either in the sensitivity of the adrenal gland to ACTH or in the
      catecholaminergic innervation of the adrenal gland. The lack of effect of sex and
      sex steroids in the ACTH secretory response to buspirone may indicate that the
      sex differences in serotonergic modulation of the HPA axis, as reported
      previously by our group, were mediated via serotonergic receptor subtypes other
      than the 1A receptor.

PMID- 16280028
TI  - Melatonin does not inhibit hypothalamic-pituitary-adrenal activity in waking
      young men.
AB  - The pineal hormone melatonin is mainly secreted during night-time which, in
      humans, is the normal time of sleep. It has been proposed that, during this
      period, melatonin exerts an inhibitory influence on secretory activity of the
      hypothalamic-pituitary-adrenal (HPA) system, although there is little evidence
      for this view in humans. In blind humans, a single oral dose of melatonin at bed
      time suppressed nocturnal cortisol secretion. However, suppression could have
      been secondary to an improved sleep after melatonin in these experiments. In the
      present study, we examined whether melatonin exerts a similar inhibitory effect
      on HPA activity in waking subjects. Fourteen healthy young men were tested at bed
      time, but kept awake throughout the experimental epoch. Thirty minutes after oral
      ingestion of 5 mg melatonin, activity of the HPA-system was stimulated through a
      standard insulin-induced hypoglycaemia. Adrenocorticotrophin hormone and cortisol
      concentrations under basal conditions before insulin injection, as well as in
      response to insulin-induced hypoglycaemia, were almost identical for the
      melatonin and placebo control conditions (P > 0.5). However, melatonin increased
      plasma prolactin concentrations (P < 0.01) and reduced systolic blood pressure in
      the time interval following hypoglycaemia (P < 0.05). Based on a review of the
      literature and our results, we conclude that melatonin per se has no
      substantially suppressing effect on HPA secretory activity, although such an
      effect can be gated by sleep-related processes.

PMID- 16280029
TI  - Pituitary-adrenal responses to cholinergic stimulation and acute mild stress are
      differentially elevated in male and female M(2) muscarinic receptor knockout
      mice.
AB  - Adrenocorticotrophic hormone (ACTH) and corticosterone responses to cholinergic
      stimulation are greater in male rats and mice than in females. To explore the
      role of M(2) muscarinic receptors in this sex difference, we administered the
      nonselective muscarinic agonist, oxotremorine, the acetylcholinesterase
      inhibitor, physostigmine, and saline (a mild stressor) to male and female M(2)
      receptor knockout (KO) and wild-type (WT) mice of the same genetic background.
      Because M(2) receptors function primarily as presynaptic autoreceptors, we
      hypothesized that their absence in M(2) KO mice would increase the sensitivity of
      hormone responses to cholinergic stimulation in these groups. Both male and
      female M(2) KO mice were significantly more responsive to the stress of saline
      injection than were their WT counterparts. Oxotremorine and physostigmine
      increased ACTH and corticosterone in all four groups, but to a significantly
      greater degree in KO males compared to WT males, KO females, and WT females. The
      increase in ACTH also was significantly greater in WT males compared to WT
      females. By contrast, the increase in corticosterone was significantly more in
      females compared to males, independent of genotype. Following pretreatment with
      the nonselective muscarinic antagonist, scopolamine, ACTH and corticosterone
      responses to oxotremorine and to saline in the M(2) KO mice were comparable with
      those of their WT counterparts. These findings suggest that the M(2) muscarinic
      receptor subtype influences male and female pituitary-adrenal responses following
      stimulation by both mild stress and cholinergic drugs. The M(2) receptor appears
      to regulate ACTH responses to cholinergic stimulation in males but not in
      females; however, other muscarinic receptors may be involved because
      corticosterone responses were higher in females compared to males. Because ACTH
      and corticosterone responses were greater in male and female M(2) KO mice, the
      M(2) receptor appears to dampen the stress response.

PMID- 16280030
TI  - Expression of mRNA for prolactin receptor (long form) in dopamine and pro
      opiomelanocortin neurones in the arcuate nucleus of non-pregnant and lactating
      rats.
AB  - Under most conditions, prolactin secretion from the pituitary gland is subject to
      negative-feedback regulation. Prolactin stimulates dopamine release from
      tuberoinfundibular (TIDA) neurones in the arcuate nucleus of the hypothalamus,
      which in turn suppresses the production of prolactin. However, during late
      pregnancy and continuing into lactation, this feedback mechanism becomes less
      responsive to prolactin and, as a result, a hyperprolactinaemic state develops.
      We investigated whether long-form prolactin receptor (PRL-R(L)) mRNA is present
      on TIDA neurones in nonpregnant and lactating rats. In addition, we examined
      whether PRL-R(L) mRNA is colocalized on hypothalamic pro-opiomelanocortin (POMC)
      neurones. Dual-label in situ hybridizations using an (35)S-labelled cRNA probe
      specific for long-form PRL-R, together with a digoxigenin-labelled RNA probe that
      encoded either tyrosine hydroxylase (TH) or POMC mRNA, were performed on brain
      sections. In both nonpregnant and lactating rats, the majority of TH mRNA
      positive cells (> 90%) were found to express long-form PRL-R mRNA. In sections
      from nonpregnant rats, few non-TH positive cells expressed PRL-R(L) mRNA. By
      contrast, during lactation, the proportion of PRL-R(L) mRNA-positive cells that
      were not TH mRNA-positive increased to approximately 70%. Only a small number of
      neurones in this subpopulation of PRL-R(L) mRNA-positive neurones were found to
      be positive for POMC mRNA. These data show that the loss of responsiveness to
      prolactin occurring during lactation is not due to down regulation of long-form
      PRL-R gene expression on TIDA neurones. Moreover, the persistent expression of
      PRL-R(L) in arcuate neuroendocrine circuits suggests that PRL-R-mediated
      signalling continues to be important in these neurones during lactation.

PMID- 16280031
TI  - Dopamine D(2)-like receptor function is converted from excitatory to inhibitory
      by thyroxine in the developmental hippocampus.
AB  - The mechanism by which a lack of thyroid hormone in the early development of the
      brain causes permanent mental retardation in cretins is currently unknown. On the
      other hand, an abnormality in dopamine-related brain function is believed to
      underlie some forms of mental illness. In this study, we demonstrate that
      although the activation of a dopaminergic D(2)-like receptor inhibited
      glutamatergic transmission in the hippocampal slices of normal adult rats,
      indicating the inhibitory action of the D(2)-like receptor on glutamatergic
      transmission, it markedly enhanced glutamatergic transmission both in a mutant
      hypothyroid rat with a missense mutation in thyroglobulin and in hypothyroid rats
      treated with methylmercaptoimidazole (MMI), indicating the excitatory action of
      the D(2)-like receptor on glutamatergic transmission. Paired pulse facilitation
      of field excitatory postsynaptic potentials was reduced by the activation of the
      D(2)-like receptors from MMI-induced hypothyroid rats, suggesting a presynaptic
      locus of the excitatory action of the D(2)-like receptors. In normal rats, the
      excitatory D(2)-like dopamine receptors were observed in the developing stages
      and were completely replaced by normal inhibitory responses up to adulthood.
      Furthermore, the continuous supplement of thyroxine from birth exerted a
      normalising effect on the abnormal excitatory property of D(2)-like dopamine
      receptors in the hippocampal slices of MMI-treated hypothyroid rats. From these
      results, it is suggested that thyroxine may play a crucial role in reversing the
      excitatory property of D(2)-like dopaminergic receptors in the immature brain to
      an inhibitory one in the mature brain. Moreover, we suggest that the abnormal
      excitatory property of D(2)-like dopaminergic receptors may develop in response
      to a lack of thyroxine and may contribute to some central nervous system
      deficits, including cognitive dysfunctions accompanied by hypothyroidism.

PMID- 16280032
TI  - Effect of exercise on ovarian morphology and expression of nerve growth factor
      and alpha(1)- and beta(2)-adrenergic receptors in rats with steroid-induced
      polycystic ovaries.
AB  - Oestadiol valerate (EV)-induced polycystic ovaries (PCO) in rats cause
      anovulation and cystic ovarian morphology. Denervation of ovarian sympathetic
      nerves restores ovulatory disruption. In the present study, we determined whether
      5 weeks of voluntary exercise influence ovarian morphology and the expression of
      sympathetic markers in the EV-induced PCO rat model. The effect of exercise on
      (i) ovarian morphology; (ii) mRNA and protein expression of nerve growth factor
      (NGF); and (iii) mRNA and number of ovarian-expressing cells for the NGF receptor
      (p75 neurotrophin receptor) and the alpha(1a)-, alpha(1b)-, alpha(1d)- and
      beta(2)-adrenergic receptors (ARs) in rats with EV-induced PCO was evaluated. PCO
      was induced by a single i.m. injection of EV, and controls were injected with oil
      alone in adult cycling rats. The rats were divided into four groups: (i) control
      (oil); (ii) exercise group (oil + exercise); (iii) a PCO group (EV); and (iv) a
      PCO exercise group (EV + exercise). The exercise and PCO exercise groups ran
      voluntarily for 5 weeks in computer-monitored wheels placed in the cages where
      they were housed. The results obtained indicated that ovarian morphology was
      almost normalised in the PCO exercise group; NGF mRNA and protein concentrations
      were normalised in the PCO exercise group; high numbers of NGF receptor
      expressing cells in PCO ovaries were lowered by exercise; and the number of
      immunopositive cells of the different AR subtypes were all reduced after exercise
      in the PCO group, except for the alpha(1b)- and beta(2)-AR whereas the mRNA
      levels were unaffected, indicating transcriptional regulation. In conclusion, our
      data indicate a beneficial effect of regular exercise, as a modulator of ovarian
      sympathetic innervation, in the prevention and treatment of human PCOS.

PMID- 16280033
TI  - The estrogen receptor-alpha A908G (K303R) mutation occurs at a low frequency in
      invasive breast tumors: results from a population-based study.
AB  - INTRODUCTION: Evidence suggests that alterations in estrogen signaling pathways,
      including estrogen receptor-alpha (ER-alpha), occur during breast cancer
      development. A point mutation in ER-alpha (nucleotide A908G), producing an amino
      acid change from lysine to arginine at codon 303 (K303R) results in receptor
      hypersensitivity to estrogen. This mutation was initially reported in one-third
      of hyperplastic benign breast lesions, although several recent studies failed to
      detect it in benign or malignant breast tissues. METHODS: We screened 653
      microdissected, newly diagnosed invasive breast tumors from patients in the
      Carolina Breast Cancer Study, a population-based case-control study of breast
      cancer in African American and white women in North Carolina, for the presence of
      the ER-alpha A908G mutation by using single-strand conformational polymorphism
      (SSCP) analysis and 33P-cycle sequencing. RESULTS: We detected the ER-alpha A908G
      mutation in 37 of 653 (5.7%) breast tumors. The absence of this mutation in
      germline DNA confirmed it to be somatic. Three tumors exhibited only the mutant G
      base at nucleotide 908 on sequencing, indicating that the wild-type ER-alpha
      allele had been lost. The ER-alpha A908G mutation was found more frequently in
      higher-grade breast tumors (odds ratio (OR) 2.83; 95% confidence interval (CI)
      1.09 to 7.34, grade II compared with grade I), and in mixed lobular/ductal tumors
      (OR 2.10; 95% CI 0.86 to 5.12) compared with ductal carcinomas, although the
      latter finding was not statistically significant. CONCLUSION: This population
      based study, the largest so far to screen for the ER-alpha A908G mutation in
      breast cancer, confirms the presence of the mutant in invasive breast tumors. The
      mutation was associated with higher tumor grade and mixed lobular/ductal breast
      tumor histology.

PMID- 16280034
TI  - Cortactin overexpression results in sustained epidermal growth factor receptor
      signaling by preventing ligand-induced receptor degradation in human carcinoma
      cells.
AB  - The chromosome 11q13 region is frequently amplified in human carcinomas and
      results in an increased expression of various genes including cortactin, and is
      also associated with an increased invasive potential. Cortactin acts as an
      important regulator of the actin cytoskeleton. It is therefore very tempting to
      speculate that cortactin is the crucial gene within the 11q13 amplicon that
      mediates the invasive potential of these carcinomas. Cortactin also participates
      in receptor-mediated endocytosis, and recent findings have shown that, during
      receptor internalization, cortactin overexpression inhibits the ubiquitylation
      mediated degradation of the epidermal growth factor receptor, resulting in a
      sustained ligand-induced epidermal growth factor receptor activity.

PMID- 16280035
TI  - Selective estrogen receptor modulators inhibit growth and progression of
      premalignant lesions in a mouse model of ductal carcinoma in situ.
AB  - INTRODUCTION: Ductal carcinoma in situ (DCIS) is a noninvasive premalignant
      lesion and is considered a precursor to invasive carcinoma. DCIS accounts for
      nearly 20% of newly diagnosed breast cancer, but the lack of experimentally
      amenable in vivo DCIS models hinders the development of treatment strategies.
      Here, we demonstrate the utility of a mouse transplantation model of DCIS for
      chemoprevention studies using selective estrogen receptor modulators (SERMs).
      This model consists of a set of serially transplanted lines of genetically
      engineered mouse mammary intraepithelial neoplasia (MIN) outgrowth (MIN-O) tissue
      that have stable characteristics. We studied the ovarian-hormone-responsiveness
      of one of the lines with a particular focus on the effects of two related SERMs,
      tamoxifen and ospemifene. METHODS: The estrogen receptor (ER) status and ovarian
      hormone-dependence of the mouse MIN outgrowth tissue were determined by
      immunohistochemistry and ovarian ablation. The effects of tamoxifen and
      ospemifene on the growth and tumorigenesis of MIN outgrowth were assessed at 3
      and 10 weeks after transplantation. The effects on ER status, cell proliferation,
      and apoptosis were studied with immunohistochemistry. RESULTS: The MIN-O was ER
      positive and ovarian ablation resulted in reduced MIN-O growth and tumor
      development. Likewise, tamoxifen and ospemifene treatments decreased the MIN
      growth and tumor incidence in comparison with the control (P < 0.01). Both SERMs
      significantly decreased cell proliferation. Between the two SERM treatment
      groups, there were no statistically significant differences in MIN-O size, tumor
      latency, or proliferation rate. In contrast, the ospemifene treatment
      significantly increased ER levels while tamoxifen significantly decreased them.
      CONCLUSION: Tamoxifen and ospemifene inhibit the growth of premalignant mammary
      lesions and the progression to invasive carcinoma in a transplantable mouse model
      of DCIS. The inhibitory effects of these two SERMs are similar except for their
      effects on ER modulation. These differences in ER modulation may suggest
      different mechanisms of action between the two related SERMs and may portend
      different long-term outcomes. These data demonstrate the value of this model
      system for preclinical testing of antiestrogen or other therapies designed to
      prevent or delay the malignant transformation of premalignant mammary lesions in
      chemoprevention.

PMID- 16280036
TI  - Genetic polymorphisms in human SULT1A1 and UGT1A1 genes associate with breast
      tumor characteristics: a case-series study.
AB  - INTRODUCTION: Estrogens are important in breast cancer development. SULT1A1 and
      UGT1A1 catalyze estrogen metabolism and are polymorphic. The SULT1A1*2 protein
      exhibits low activity, and a TA repeat within the UGT1A1 promoter alters the
      level of expression of the protein. We hypothesized that the SULT1A1*2 allozyme
      has decreased capacity to sulfate estrogens, that the SULT1A1*2 allele conferred
      increased capacity of cells to proliferate in response to estrogens, and that
      individuals with the variant SULT1A1 and UGT1A1 genotypes exhibited different
      breast tumor characteristics. METHODS: The capacity for SULT1A1*2 to sulfate
      17beta-estradiol and the capacity for cells expressing SULT1A1*1 or SULT1A1*2 to
      proliferate in response to 17beta-estradiol was evaluated. A case-series study
      was performed in a total of 210 women with incident breast cancer, including 177
      Caucasians, 25 African-Americans and eight women of other ethnic background. The
      SULT1A1 and UGT1A1 genotypes were determined and a logistic regression model was
      used to analyze genotype-phenotype associations. RESULTS: We determined that the
      SULT1A1*1/*1 high-activity genotype was associated with tumor size <or=2 cm (odds
      ratio = 2.63, 95% confidence interval = 1.25-5.56, P = 0.02). Individuals with
      low-activity UGT1A1 genotypes (UGT1A1*28/*28 or UGT1A1*28/*34) were more likely
      to have an age at diagnosis >or=60 years (odds ratio = 3.70, 95% confidence
      interval = 1.33-10.00, P = 0.01). Individuals with both SULT1A1 and UGT1A1 high
      activity genotypes had low tumor grade (odds ratio = 2.56, 95% confidence
      interval = 1.04-6.25, P = 0.05). Upon stratification by estrogen receptor status,
      significant associations were observed predominantly in estrogen receptor
      negative tumors. CONCLUSION: The data suggest that genetic variation in SULT1A1
      and UGT1A1 may influence breast cancer characteristics and might be important for
      breast cancer prognosis.

PMID- 16280037
TI  - CYP17 gene polymorphism in relation to breast cancer risk: a case-control study.
AB  - INTRODUCTION: The c.1-34T>C 5' promoter region polymorphism in cytochrome P450c17
      (CYP17), a key enzyme in the biosynthesis of estrogen, has been associated with
      breast cancer risk, but most previous studies have been relatively small.
      METHODS: We genotyped 1,544 incident cases of primary breast cancer and 1,502
      population controls, all postmenopausal Swedish women, for the CYP17 c.1-34T>C
      polymorphism and calculated odds ratios (ORs) and 95% confidence intervals (CIs)
      from logistic regression models. RESULTS: No overall association was found
      between CYP17 c.1-34T>C and breast cancer risk, OR 1.0 (95% CI 0.8-1.3) for the
      A2/A2 (CC) carriers compared to the A1/A1 (TT) carriers, regardless of
      histopathology. We detected an interaction between CYP17 c.1-34T>C and age at
      menarche (P = 0.026) but regarded that as a chance finding as no dose-response
      pattern was evident. Other breast cancer risk factors, including menopausal
      hormone use and diabetes mellitus, did not modify the overall results.
      CONCLUSION: It is unlikely that CYP17 c.1-34T>C has a role in breast cancer
      etiology, overall or in combination with established non-genetic breast cancer
      risk factors.

PMID- 16280038
TI  - CYP17 and breast cancer: no overall effect, but what about interactions?
AB  - Three large studies published in recent issues of Breast Cancer Research reported
      no overall evidence of an association between the CYP17 5'-untranslated region
      MspA1 polymorphism and breast cancer. The present commentary briefly highlights a
      few important observations and discusses some additional approaches to further
      assessment of associations between CYP17 common variants and breast cancer risk.
      In particular, the evolution of evidence on breast cancer and the CYP17 MspA1
      variant suggests that determination of possible interactions between gene
      variants postulated to influence risk and nongenetic risk factors would be more
      efficiently accomplished by pooled analyses, ideally involving all studies of
      breast cancer, than by attempting to synthesize published information.
      Furthermore, such analyses would also be relevant to investigation of potential
      gene-gene interactions between CYP17 and other common variants in genes encoding
      enzymes that are involved in the synthesis and inactivation of sex steroid
      hormones, preferably using optimal sets of single nucleotide polymorphisms.

PMID- 16280039
TI  - Clioquinol and pyrrolidine dithiocarbamate complex with copper to form proteasome
      inhibitors and apoptosis inducers in human breast cancer cells.
AB  - INTRODUCTION: A physiological feature of many tumor tissues and cells is the
      tendency to accumulate high concentrations of copper. While the precise role of
      copper in tumors is cryptic, copper, but not other trace metals, is required for
      angiogenesis. We have recently reported that organic copper-containing compounds,
      including 8-hydroxyquinoline-copper(II) and 5,7-dichloro-8-hydroxyquinoline
      copper(II), comprise a novel class of proteasome inhibitors and tumor cell
      apoptosis inducers. In the current study, we investigate whether clioquinol (CQ),
      an analog of 8-hydroxyquinoline and an Alzheimer's disease drug, and pyrrolidine
      dithiocarbamate (PDTC), a known copper-binding compound and antioxidant, can
      interact with copper to form cancer-specific proteasome inhibitors and apoptosis
      inducers in human breast cancer cells. Tetrathiomolybdate (TM), a strong copper
      chelator currently being tested in clinical trials, is used as a comparison.
      METHODS: Breast cell lines, normal, immortalized MCF-10A, premalignant
      MCF10AT1K.cl2, and malignant MCF10DCIS.com and MDA-MB-231, were treated with CQ
      or PDTC with or without prior interaction with copper, followed by measurement of
      proteasome inhibition and cell death. Inhibition of the proteasome was determined
      by levels of the proteasomal chymotrypsin-like activity and ubiquitinated
      proteins in protein extracts of the treated cells. Apoptotic cell death was
      measured by morphological changes, Hoechst staining, and poly(ADP-ribose)
      polymerase cleavage. RESULTS: When in complex with copper, both CQ and PDTC, but
      not TM, can inhibit the proteasome chymotrypsin-like activity, block
      proliferation, and induce apoptotic cell death preferentially in breast cancer
      cells, less in premalignant breast cells, but are non-toxic to normal/non
      transformed breast cells at the concentrations tested. In contrast, CQ, PDTC, TM
      or copper alone had no effects on any of the cells. Breast premalignant or cancer
      cells that contain copper at concentrations similar to those found in patients,
      when treated with just CQ or PDTC alone, but not TM, undergo proteasome
      inhibition and apoptosis. CONCLUSION: The feature of breast cancer cells and
      tissues to accumulate copper can be used as a targeting method for anticancer
      therapy through treatment with novel compounds such as CQ and PDTC that become
      active proteasome inhibitors and breast cancer cell killers in the presence of
      copper.

PMID- 16280040
TI  - Targeted therapy against Bcl-2-related proteins in breast cancer cells.
AB  - INTRODUCTION: Bcl-2 and Bcl-xL confer resistance to apoptosis, thereby reducing
      the effectiveness of chemotherapy. We examined the relationship between the
      expression of Bcl-2 and Bcl-xL and chemosensitivity of breast cancer cells, with
      the aim of developing specific targeted therapy. METHODS: Four human breast
      cancer cell lines were examined, and the effects of antisense (AS) Bcl-2 and AS
      Bcl-xL phosphorothioate oligodeoxynucleotides (ODNs) on chemosensitivity were
      tested in vitro and in vivo. Chemosensitivity was evaluated by the MTT (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay, and the
      antitumor effect was assessed in vivo by the success of xenograft transplantation
      into athymic mice. RESULTS: Treatment with AS Bcl-2 and Bcl-xL ODNs resulted in a
      sequence-specific decrease in protein expression, compared with controls.
      Treatment of BT-474, ZR-75-1, and MDA-MB-231 cells with AS Bcl-2 increased
      chemosensitivity to doxorubicin (DOX), mitomycin C (MMC), paclitaxel (TXL), and
      docetaxel (TXT). Transfection of the Bcl-2 gene into MDA-MB-453 cells decreased
      sensitivity to DOX and MMC. Treatment of MDA-MB-231, BT-474, and ZR-75-1 cells
      with AS Bcl-xL increased chemosensitivity to DOX, MMC and taxanes to a smaller
      extent than AS Bcl-2. This occurred in the setting of increased Bax and cleaved
      poly(ADP-ribose) polymerase, as well as decreased Bcl-2 and pAkt. AS Bcl-2 ODNs
      induced splenomegaly in association with increased serum IL-12, which was
      attenuated by methylation of the CpG motifs of AS Bcl-2; however, methylated CpG
      failed to negate the increased antitumor effect of AS Bcl-2. Bcl-2 and Bcl-xL, to
      a smaller extent, are major determinants of chemosensitivity in breast cancer
      cells. CONCLUSION: Targeted therapy against Bcl-2 protein with the use of AS ODNs
      might enhance the effects of chemotherapy in patients with breast cancer.

PMID- 16280041
TI  - Evolutionary conservation analysis increases the colocalization of predicted
      exonic splicing enhancers in the BRCA1 gene with missense sequence changes and in
      frame deletions, but not polymorphisms.
AB  - INTRODUCTION: Aberrant pre-mRNA splicing can be more detrimental to the function
      of a gene than changes in the length or nature of the encoded amino acid
      sequence. Although predicting the effects of changes in consensus 5' and 3'
      splice sites near intron:exon boundaries is relatively straightforward,
      predicting the possible effects of changes in exonic splicing enhancers (ESEs)
      remains a challenge. METHODS: As an initial step toward determining which ESEs
      predicted by the web-based tool ESEfinder in the breast cancer susceptibility
      gene BRCA1 are likely to be functional, we have determined their evolutionary
      conservation and compared their location with known BRCA1 sequence variants.
      RESULTS: Using the default settings of ESEfinder, we initially detected 669
      potential ESEs in the coding region of the BRCA1 gene. Increasing the threshold
      score reduced the total number to 464, while taking into consideration the
      proximity to splice donor and acceptor sites reduced the number to 211.
      Approximately 11% of these ESEs (23/211) either are identical at the nucleotide
      level in human, primates, mouse, cow, dog and opossum Brca1 (conserved) or are
      detectable by ESEfinder in the same position in the Brca1 sequence (shared). The
      frequency of conserved and shared predicted ESEs between human and mouse is
      higher in BRCA1 exons (2.8 per 100 nucleotides) than in introns (0.6 per 100
      nucleotides). Of conserved or shared putative ESEs, 61% (14/23) were predicted to
      be affected by sequence variants reported in the Breast Cancer Information Core
      database. Applying the filters described above increased the colocalization of
      predicted ESEs with missense changes, in-frame deletions and unclassified
      variants predicted to be deleterious to protein function, whereas they decreased
      the colocalization with known polymorphisms or unclassified variants predicted to
      be neutral. CONCLUSION: In this report we show that evolutionary conservation
      analysis may be used to improve the specificity of an ESE prediction tool. This
      is the first report on the prediction of the frequency and distribution of ESEs
      in the BRCA1 gene, and it is the first reported attempt to predict which ESEs are
      most likely to be functional and therefore which sequence variants in ESEs are
      most likely to be pathogenic.

PMID- 16280043
TI  - CYP2D6 variants and the prediction of tamoxifen response in randomized patients:
      author response.

PMID- 16280042
TI  - Gene expression profiling spares early breast cancer patients from adjuvant
      therapy: derived and validated in two population-based cohorts.
AB  - INTRODUCTION: Adjuvant breast cancer therapy significantly improves survival, but
      overtreatment and undertreatment are major problems. Breast cancer expression
      profiling has so far mainly been used to identify women with a poor prognosis as
      candidates for adjuvant therapy but without demonstrated value for therapy
      prediction. METHODS: We obtained the gene expression profiles of 159 population
      derived breast cancer patients, and used hierarchical clustering to identify the
      signature associated with prognosis and impact of adjuvant therapies, defined as
      distant metastasis or death within 5 years. Independent datasets of 76 treated
      population-derived Swedish patients, 135 untreated population-derived Swedish
      patients and 78 Dutch patients were used for validation. The inclusion and
      exclusion criteria for the studies of population-derived Swedish patients were
      defined. RESULTS: Among the 159 patients, a subset of 64 genes was found to give
      an optimal separation of patients with good and poor outcomes. Hierarchical
      clustering revealed three subgroups: patients who did well with therapy, patients
      who did well without therapy, and patients that failed to benefit from given
      therapy. The expression profile gave significantly better prognostication (odds
      ratio, 4.19; P = 0.007) (breast cancer end-points odds ratio, 10.64) compared
      with the Elston-Ellis histological grading (odds ratio of grade 2 vs 1 and grade
      3 vs 1, 2.81 and 3.32 respectively; P = 0.24 and 0.16), tumor stage (odds ratio
      of stage 2 vs 1 and stage 3 vs 1, 1.11 and 1.28; P = 0.83 and 0.68) and age (odds
      ratio, 0.11; P = 0.55). The risk groups were consistent and validated in the
      independent Swedish and Dutch data sets used with 211 and 78 patients,
      respectively. CONCLUSION: We have identified discriminatory gene expression
      signatures working both on untreated and systematically treated primary breast
      cancer patients with the potential to spare them from adjuvant therapy.

PMID- 16280044
TI  - Positive association between mammographic breast density and bone mineral density
      in the Postmenopausal Estrogen/Progestin Interventions Study.
AB  - INTRODUCTION: Mammographic breast density is a strong independent risk factor for
      breast cancer. We hypothesized that demonstration of an association between
      mammographic breast density and bone mineral density (BMD) would suggest a
      unifying underlying mechanism influencing both breast density and BMD. METHODS:
      In a cross-sectional analysis of baseline data from the Postmenopausal
      Estrogen/Progestin Interventions Study (PEPI), participants were aged 45 to 64
      years and were at least 1 year postmenopausal. Mammographic breast density
      (percentage of the breast composed of dense tissue), the outcome, was assessed
      with a computer-assisted percentage-density method. BMD, the primary predictor,
      was measured with dual-energy X-ray absorptiometry. Women quitting menopausal
      hormone therapy to join PEPI were designated recent hormone users. RESULTS: The
      mean age of the 594 women was 56 years. The average time since menopause was 5.6
      years. After adjustment for age, body mass index, and cigarette smoking, in women
      who were not recent hormone users before trial enrollment (n = 415), mammographic
      density was positively associated with total hip (P = 0.04) and lumbar (P = 0.08)
      BMD. Mammographic density of recent hormone users (n = 171) was not significantly
      related to either total hip (P = 0.51) or lumbar (P = 0.44) BMD. In participants
      who were not recent hormone users, mammographic density was 4% greater in the
      highest quartile of total hip BMD than in the lowest. In participants who were
      not recent hormone users, mammographic density was 5% greater in the highest
      quartile of lumbar spine BMD than in the lowest. CONCLUSION: Mammographic density
      and BMD are positively associated in women who have not recently used
      postmenopausal hormones. A unifying biological mechanism may link mammographic
      density and BMD. Recent exogenous postmenopausal hormone use may obscure the
      association between mammographic density and BMD by having a persistent effect on
      breast tissue.

PMID- 16280045
TI  - Quantification of the response of circulating epithelial cells to neodadjuvant
      treatment for breast cancer: a new tool for therapy monitoring.
AB  - INTRODUCTION: In adjuvant treatment for breast cancer there is no tool available
      with which to measure the efficacy of the therapy. In contrast, in neoadjuvant
      therapy reduction in tumour size is used as an indicator of the sensitivity of
      tumour cells to the agents applied. If circulating epithelial (tumour) cells can
      be shown to react to therapy in the same way as the primary tumour, then this
      response may be exploited to monitor the effect of therapy in the adjuvant
      setting. METHOD: We used MAINTRAC analysis to monitor the reduction in
      circulating epithelial cells during the first three to four cycles of neoadjuvant
      therapy in 30 breast cancer patients. RESULTS: MAINTRAC analysis revealed a
      patient-specific response. Comparison of this response with the decline in size
      of the primary tumour showed that the reduction in number of circulating
      epithelial cells accurately predicted final tumour reduction at surgery if the
      entire neoadjuvant regimen consisted of chemotherapy. However, the response of
      the circulating tumour cells was unable to predict the response to additional
      antibody therapy. CONCLUSION: The response of circulating epithelial cells
      faithfully reflects the response of the whole tumour to adjuvant therapy,
      indicating that these cells may be considered part of the tumour and can be used
      for therapy monitoring.

PMID- 16280046
TI  - Rac1 and Rac3 isoform activation is involved in the invasive and metastatic
      phenotype of human breast cancer cells.
AB  - INTRODUCTION: The metastatic progression of cancer is a direct result of the
      disregulation of numerous cellular signaling pathways, including those associated
      with adhesion, migration, and invasion. Members of the Rac family of small
      GTPases are known to act as regulators of actin cytoskeletal structures and
      strongly influence the cellular processes of integrin-mediated adhesion and
      migration. Even though hyperactivated Rac proteins have been shown to influence
      metastatic processes, these proteins have never been directly linked to
      metastatic progression. METHODS: To investigate a role for Rac and Cdc42 in
      metastatic breast cancer cell invasion and migration, relative endogenous Rac or
      Cdc42 activity was determined in a panel of metastatic variants of the MDA-MB-435
      metastatic human breast cancer cell line using a p21-binding domain-PAK pull down
      assay. To investigate the migratory and invasive potential of the Rac isoforms in
      human breast cancer, namely Rac1 and the subsequently cloned Rac3, we stably
      expressed either dominant active Rac1 or dominant active Rac3 into the least
      metastatic cell variant. Dominant negative Rac1 or dominant negative Rac3 were
      stably expressed in the most metastatic cell variant. Cell lines expressing
      mutant Rac1 or Rac3 were analyzed using in vitro adhesion, migration and invasion
      assays. RESULTS: We show that increased activation of Rac proteins directly
      correlates with increasing metastatic potential in a panel of cell variants
      derived from a single metastatic breast cancer cell line (MDA-MB-435). The same
      correlation could not be found with activated Cdc42. Expression of a dominant
      active Rac1 or a dominant active Rac3 resulted in a more invasive and motile
      phenotype. Moreover, expression of either dominant negative Rac1 or dominant
      negative Rac3 into the most metastatic cell variant resulted in decreased
      invasive and motile properties. CONCLUSION: This study correlates endogenous Rac
      activity with high metastatic potential and implicates Rac in the regulation of
      cell migration and invasion in metastatic breast cancer cells. Taken together,
      these results suggest a role for both the Rac1 and Rac3 GTPases in human breast
      cancer progression.

PMID- 16280047
TI  - What does an orphan G-protein-coupled receptor have to do with estrogen?
AB  - Estrogen affects multiple aspects of human physiology, including the normal
      growth and development of female reproductive tissues, bone integrity,
      cardiovascular and central nervous system functions, and plays a central role in
      normal mammary development and breast pathogenesis. It modulates diverse cell
      signaling pathways, some of which appear to be independent of the known estrogen
      receptors (ERs). Although many of estrogen's actions can be explained by the
      nuclear ERs (ER-alpha and ER-beta) functioning as ligand-activated RNA
      transcription factors, there are numerous rapid biochemical and physiological
      responses that cannot be explained by the classical genomic effects of estrogen
      signaling. It has long been postulated that the rapid effects of estrogen are due
      to a membrane-bound ER, and two recent reports suggest that it is in fact a G
      protein-coupled receptor named 'GPR30'.

PMID- 16280048
TI  - Key stages in mammary gland development: the mammary end bud as a motile organ.
AB  - In the rodent, epithelial end buds define the tips of elongating mammary ducts.
      These highly motile structures undergo repeated dichotomous branching as they
      aggressively advance through fatty stroma and, turning to avoid other ducts, they
      finally cease growth leaving behind the open, tree-like framework on which
      secretory alveoli develop during pregnancy. This review identifies the motility
      of end buds as a unique developmental marker that represents the successful
      integration of systemic and local mammotrophic influences, and covers relevant
      advances in ductal growth regulation, extracellular matrix (ECM) remodeling, and
      cell adhesion in the inner end bud. An unexpected growth-promoting synergy
      between insulin-like growth factor-1 and progesterone, in which ducts elongate
      without forming new end buds, is described as well as evidence strongly
      supporting self-inhibition of ductal elongation by end-bud-secreted transforming
      growth factor-beta acting on stromal targets. The influence of the matrix
      metalloproteinase ECM-remodeling enzymes, notably matrix metalloproteinase-2, on
      end bud growth is discussed in the broader context of enzymes that regulate the
      polysaccharide-rich glycosaminoglycan elements of the ECM. Finally, a critical,
      motility-enabling role for the cellular architecture of the end bud is identified
      and the contribution of cadherins, the netrin/neogenin system, and ErbB2 to the
      structure and motility of end buds is discussed.

PMID- 16280049
TI  - 25-Hydroxyvitamin D3 1alpha-hydroxylase expression in breast cancer and use of
      non-1alpha-hydroxylated vitamin D analogue.
AB  - INTRODUCTION: The cytochrome P450 mitochondrial enzyme 25-hydroxyvitamin D3
      1alpha-hydroxylase (1alpha-hydroxylase) of renal tubule cells hydroxylates the
      major circulating form of vitamin D (25(OH)D3) to the active systemic hormone
      1,25(OH)2D3. Local production of 1,25(OH)2D3 appears to occur also at other sites
      where 1alpha-hydroxylase is expressed for autocrine/paracrine regulation. To
      reduce risks of hypercalcemia during treatment with vitamin D, we have previously
      suggested use of non-1alpha-hydroxylated vitamin D analogues to target tissues
      where 1alpha-hydroxylase is expressed, including the parathyroid glands in
      secondary hyperparathyroidism. The present study was undertaken to examine
      expression of 1alpha-hydroxylase in breast cancer and to investigate whether a
      non-1alpha-hydroxylated vitamin D analogue displayed biological function. In
      addition, expression of the 25-hydroxyvitamin D3 24-hydroxylase (24-hydroxylase)
      and the vitamin D receptor (VDR) was investigated. METHODS: The expression of
      1alpha-hydroxylase, 24-hydroxylase and VDR was investigated in breast cancer
      specimens (n = 19) and normal breast tissues (n = 10) by immunohistochemistry
      and/or RT-PCR. Consecutive cryosections of 6 mum essentially free of immune cells
      were used in the analyses. The effect of vitamin D analogues on transcriptional
      activation was analyzed in transiently transfected MCF-7 breast cancer cells.
      RESULTS: 1alpha-hydroxylase protein was demonstrated in 79% and 100% of breast
      cancer specimens and normal breast, respectively. The overall relative mRNA
      levels of 1alpha-hydroxylase and 24-hydroxylase in normal breast compared to
      breast tumors were: 1alpha-hydroxylase, 1 +/- 0.07 versus 0.7 +/- 0.05,
      respectively (p < 0.001); 24-hydroxylase, 1 +/- 0.08 verus 2.1 +/- 0.2,
      respectively (p < 0.001). The VDR was expressed in 95% of the tumors as expected,
      with mRNA levels of 1 +/- 0.09 and 1.4 +/- 0.12 (p < 0.05) in breast cancer and
      normal breast, respectively. The ketoconazole-sensitive transcription activation
      potential of the non-1alpha-hydroxylated vitamin D analogue prodrug of EB1089
      (EB1285) was demonstrated in MCF-7 cells, which express 1alpha-hydroxylase. The
      activity of EB1285 was about 20% of 1,25(OH)2D3. CONCLUSION: These results
      demonstrate nearly normal expression levels of 1alpha-hydroxylase, 24-hydroxylase
      and VDR in the majority of investigated breast cancer specimens. A non-1alpha
      hydroxylated vitamin D analogue displayed activity in breast cancer cells. Such
      analogues may present future therapeutic options for proliferative disorders
      where 1alpha-hydroxylase is expressed.

PMID- 16280050
TI  - XRCC1 and XPD genetic polymorphisms, smoking and breast cancer risk in a Finnish
      case-control study.
AB  - INTRODUCTION: It has been suggested that individuals with reduced DNA repair
      capacities might have increased susceptibility to environmentally induced cancer.
      In this study, we evaluated if polymorphisms in DNA repair genes XRCC1
      (Arg280His, Arg399Gln) and XPD (Lys751Gln) modify individual breast cancer risk,
      with emphasis on tobacco smoking. METHODS: The study population consisted of 483
      incident breast cancer cases and 482 population controls of Finnish Caucasian
      origin. The genotypes were determined by PCR-RFLP-based methods. Odds ratio (OR)
      and confidence intervals (CIs) were calculated by unconditional logistic
      regression analyses. RESULTS: No statistically significant overall effect in the
      breast cancer risk was seen for any of the studied polymorphisms. However, a
      significant increase in breast cancer risk was seen among ever smoking women if
      they carried at least one XRCC1-399 Gln allele (OR 2.33, 95% CI 1.30-4.19, pint
      0.025) or XPD-751 Gln/Gln genotype (OR 2.52, 95% CI 1.27-5.03, pint 0.011)
      compared to smoking women not carrying these genotypes. The risks were found to
      be confined to women smoking at least five pack-years; the respective ORs were
      4.14 (95% CI 1.66-10.3) and 4.41 (95% CI 1.62-12.0). Moreover, a significant
      trend of increasing risk with increasing number of the putative at-risk genotypes
      (p for trend 0.042) was seen. Women with at least two at-risk genotypes had an OR
      of 1.54 (95% CI 1.00-2.41) compared to women with no at-risk genotypes. Even
      higher estimates were seen for ever actively smoking women with at least two at
      risk genotypes. CONCLUSION: Our results do not indicate a major role for XRCC1
      and XPD polymorphisms in breast cancer susceptibility, but suggest that they may
      modify the risk especially among smoking women.

PMID- 16280051
TI  - Clinical trial update: International Breast Cancer Study Group.
AB  - The International Breast Cancer Study Group (IBCSG) has been conducting large,
      phase III clinical trials since 1978. Prior to 1986, these activities were
      carried out under the name of Ludwig Breast Cancer Study Group. Seven trials of
      adjuvant therapies are currently open for patient accrual, five of which are
      described in this report. The IBCSG has been a leader in the field of tailored
      treatment approaches for specific subpopulations of patients with breast cancer,
      believing that what is best for the majority may not be best for a defined
      minority.

PMID- 16280052
TI  - Patterns of reduced nipple aspirate fluid production and ductal lavage
      cellularity in women at high risk for breast cancer.
AB  - INTRODUCTION: Nipple aspiration is a noninvasive technique for obtaining breast
      fluids from the duct openings of the nipple for the evaluation of abnormalities
      associated with breast cancer. Nipple aspirate fluid (NAF) can be elicited from
      48 to 94% of healthy women, and its production has been linked to an increased
      relative risk for breast cancer development. NAF production has been used in
      studies to guide the selection of ducts for ductal lavage, a procedure in which
      ducts are cannulated and flushed with saline to collect cells. In a previous
      multicenter trial to evaluate intraductal approaches in women at high-risk for
      breast cancer, NAF production was observed in 84% of the subjects. However, we
      observed a significantly lower proportion of fluid-yielding subjects in a similar
      series of high-risk women. The purpose of the present study was to identify
      variables associated with this reduction. METHOD: Nipple aspiration was performed
      on 33 high-risk women (defined as having a 5-year Gail model index of more than
      1.7, a personal or family history of breast cancer, and/or a BRCA1 or BRCA2
      germline mutation) to identify ductal orifices for lavage procedures. Lavage was
      performed on all fluid-yielding ducts and on nine non-fluid-yielding ducts.
      RESULTS: Fluid-yielding ducts were identified in 12 of 33 (36%) of the subjects
      in the present series, compared with 16 of 19 (84%) of the subjects undergoing
      identical procedures at our facility during a multicenter trial (P = 0.001).
      Reduced NAF yields were associated with postmenopausal status (P = 0.02), BRCA
      germline mutations (P = 0.004), and risk reduction therapies, including bilateral
      salpingo-oophorectomy (BSO) and/or selective estrogen receptor modulators (SERMs;
      P = 0.009). All nine (100%) of the ductal lavage specimens collected from non
      fluidyielding ducts were acellular, in comparison with 3 of 13 specimens from
      fluid-yielding ducts (P < .001). CONCLUSION: Analysis of high-risk women in the
      present series revealed patterns of reduced NAF production and ductal lavage
      cellularity compared with a previous multicenter trial. The present series
      included more BRCA-positive women, many of whom had undergone BSO and/or were
      using SERMs. Our data suggest that endocrine mechanisms associated with these
      risk-reducing therapies may be related to patterns of diminished breast fluid
      production.

PMID- 16280054
TI  - Expression analysis of candidate breast tumour suppressor genes on chromosome
      16q.
AB  - INTRODUCTION: Chromosome arm 16q is the second most frequent target of loss of
      heterozygosity in breast cancer and is, therefore, a candidate to contain one or
      more classic tumour suppressor genes (TSGs). E-cadherin at 16q22 was identified
      as a TSG in lobular breast cancer, but TSGs in ductal breast cancer remain
      elusive. Several genes have been suggested as potential candidates (e.g. CBFA2T3,
      CTCF and WWOX) but no inactivating mutations could be identified in these genes
      and they thus fail to fit the classic two-hit model for a TSG. With the
      completion of the human transcriptome, new candidate genes can be distinguished.
      Besides mutational inactivation, a TSG could, at least in a subset of the
      tumours, be transcriptionally suppressed or even inactivated. Studying candidate
      genes for expression and somatic mutations could thus identify the TSGs. METHODS:
      Possible candidates CBFA2T3, TERF2 and TERF2IP, FBXL8 and LRRC29 and FANCA were
      studied for insertion and deletion mutations and for expression differences using
      quantitative RT-PCR in a panel of tumour cell lines and primary tumours with and
      without loss of 16q. RESULTS: None of the genes showed mutations or obvious
      expression differences. FANCA expression increased with tumour grade. CONCLUSION:
      Apparently, the underlying genetics at chromosome 16q are complex or the TSGs
      remain to be identified. Multiple mechanisms, such as mutations, promoter
      hypermethylation or haploinsufficiency, might lead to the inactivation of a TSG.

PMID- 16280053
TI  - Mutation analysis of FANCD2, BRIP1/BACH1, LMO4 and SFN in familial breast cancer.
AB  - INTRODUCTION: Mutations in known predisposition genes account for only about a
      third of all multiple-case breast cancer families. We hypothesized that germline
      mutations in FANCD2, BRIP1/BACH1, LMO4 and SFN may account for some of the
      unexplained multiple-case breast cancer families. METHODS: The families used in
      this study were ascertained through the Kathleen Cuningham Foundation Consortium
      for Research into Familial Breast Cancer (kConFab). Denaturing high performance
      liquid chromatography (DHPLC) analysis of the coding regions of these four genes
      was conducted in the youngest affected cases of 30 to 267 non-BRCA1/2 breast
      cancer families. In addition, a further 399 index cases were also screened for
      mutations in two functionally significant regions of the FANCD2 gene and 253
      index cases were screened for two previously reported mutations in BACH1 (p. P47A
      and p. M299I). RESULTS: DHPLC analysis of FANCD2 identified six silent exonic
      variants, and a large number of intronic variants, which tagged two common
      haplotypes. One protein truncating variant was found in BRIP1/BACH1, as well as
      four missense variants, a silent change and a variant in the 3' untranslated
      region. No missense or splice site mutations were found in LMO4 or SFN. Analysis
      of the missense, silent and frameshift variants of FANCD2 and BACH1 in relatives
      of the index cases, and in a panel of controls, found no evidence suggestive of
      pathogenicity. CONCLUSION: There is no evidence that highly penetrant exonic or
      splice site mutations in FANCD2, BRIP1/BACH1, LMO4 or SFN contribute to familial
      breast cancer. Large scale association studies will be necessary to determine
      whether any of the polymorphisms or haplotypes identified in these genes
      contributes to breast cancer risk.

PMID- 16280055
TI  - A common missense variant in BRCA2 predisposes to early onset breast cancer.
AB  - INTRODUCTION: Mutations in the BRCA2 gene are one of the two major causes of
      hereditary breast cancer. Protein-truncating mutations of BRCA2 are usually
      deleterious and increase the risk of breast cancer up to 80% over a lifetime. A
      few missense mutations in BRCA2 are believed to have a similarly high penetrance,
      apart from more common neutral polymorphisms. It is often difficult to classify a
      particular sequence variant as a mutation or a polymorphism. For a deleterious
      variant, one would expect a greater allele frequency in breast cancer cases than
      in ethnic-matched controls. In contrast, neutral polymorphic variants should be
      equally frequent in the two groups. METHODS: We genotyped 3,241 cases of breast
      cancer diagnosed at under 51 years of age, unselected for family history, from 18
      hospitals throughout Poland and 2,791 ethnic-matched controls for a single BRCA2
      C5972T variant. RESULTS: The variant was present in approximately 6% of the
      Polish population. In the study, 13 women (11 cases and two controls (OR = 4.7; p
      = 0.02)) were homozygous for the variant allele. The overall odds ratio for
      breast cancer in women with a single copy of the BRCA2 C5972T variant was 1.1 (p
      = 0.7); however, the effect was significant for patients diagnosed at or before
      age 40 (OR = 1.4; p = 0.04). We reviewed the association between the BRCA2
      variant in different histologic subgroups and found the effect most pronounced in
      women who had ductal carcinoma in situ (DCIS) with micro-invasion (OR = 2.8; p <
      0.0001). CONCLUSION: The BRCA2 C5972T allele is a common variant in Poland that
      increases the risk of DCIS with micro-invasion. The homozygous state is rare but
      increases the risk of breast cancer five-fold.

PMID- 16280056
TI  - Metaplastic breast carcinomas exhibit EGFR, but not HER2, gene amplification and
      overexpression: immunohistochemical and chromogenic in situ hybridization
      analysis.
AB  - INTRODUCTION: Metaplastic breast carcinomas constitute a heterogeneous group of
      neoplasms, accounting for less than 1% of all invasive mammary carcinomas.
      Approximately 70-80% of metaplastic breast carcinomas overexpress the epidermal
      growth factor receptor (EGFR). Human epidermal growth factor receptor (HER)2 and
      EGFR have attracted much attention in the medical literature over the past few
      years owing to the fact that humanized monoclonal antibodies against HER2 and
      therapies directed against the extracellular ligand-binding domain or the
      intracellular tyrosine kinase domain of EGFR have proven successful in treating
      certain types of human cancer. We investigated whether HER2 and EGFR
      overexpression was present and evaluated gene amplification in a series of
      metaplastic breast carcinomas. METHOD: Twenty-five metaplastic breast carcinomas
      were immunohistochemically analyzed using a monoclonal antibody (31G7) for EGFR
      and two antibodies for HER2 (Herceptest and CB11) and scored using the Herceptest
      scoring system. Gene amplification was evaluated by chromogenic in situ
      hybridization using Zymed Spot-Light EGFR and HER2 amplification probe. The
      results were evaluated by bright field microscopy under 40x and 63x objective
      lenses. RESULTS: Nineteen (76%) metaplastic breast carcinomas exhibited EGFR
      ovexpression, and among these EGFR amplification (defined either by large gene
      clusters or >5 signals/nucleus in >50% of neoplastic cells) was detected in seven
      cases (37%): three carcinomas with squamous differentiation and four spindle cell
      carcinomas. One case exhibited HER2 overexpression of grade 2+ (>10% of cells
      with weak to moderate complete membrane staining), but HER2 gene amplification
      was not detected. CONCLUSION: Metaplastic breast carcinomas frequently
      overexpressed EGFR, which was associated with EGFR gene amplification in one
      third of cases. Our findings suggest that some patients with metaplastic breast
      carcinomas might benefit from novel therapies targeting EGFR. Because most
      metaplastic breast carcinomas overexpress EGFR without gene amplification,
      further studies to evaluate EGFR activating mutations are warranted.

PMID- 16280058
TI  - Reduction of D-dimer levels after therapeutic administration of antithrombin in
      acquired antithrombin deficiency of severe sepsis.
AB  - INTRODUCTION: In acute disseminated intravascular coagulation, the effect of
      antithrombin (AT) administration on elevated levels of D-dimer is not well
      established. In the present study, we report on changes in circulating levels of
      D-dimer in response to administration of AT in a series of patients with acquired
      AT deficiency due to severe sepsis. METHODS: Eight consecutive critically ill
      medical patients presenting with acute disseminated intravascular coagulation
      associated with severe sepsis/septic shock received a single bolus infusion of AT
      over 30 minutes, aiming to achieve physiological AT levels. Haemostatic
      parameters including D-dimer were assessed prior to, 6 and 24 h after AT
      administration. An average of 42 +/- 9 U/kg body weight was infused. RESULTS:
      Following AT substitution, elevated levels of D-dimer fell whereas AT levels
      rose. CONCLUSION: These observations support the notion that AT can favourably
      affect fibrin degradation accompanying disseminated intravascular coagulation of
      severe sepsis.

PMID- 16280057
TI  - Lack of evidence for qualitative treatment by disease severity interactions in
      clinical studies of severe sepsis.
AB  - INTRODUCTION: The design of clinical trials of interventions aimed at reducing
      mortality in patients with severe sepsis assumes that the relative treatment
      effect of the intervention is independent of the patients' risk for death. We
      reviewed published data from phase III clinical studies of severe sepsis to
      determine whether a relationship exists between risk for death and the relative
      benefit of the investigational agent. Such an interaction might warrant a change
      in the assumptions that underlie current trial designs. METHODS: We conducted a
      systematic review of published phase III, randomized, placebo-controlled trials
      in adult patients with sepsis, severe sepsis, or septic shock up to November
      2004. All studies enrolled patients with known or suspected infection, evidence
      of a systemic response to the infection, and one or more organ dysfunctions
      resulting from the systemic response. RESULTS: Twenty-two publications,
      investigating 17 molecular entities, fulfilled criteria for phase III or
      equivalent studies aimed at reducing mortality in adult patients with severe
      sepsis or septic shock. Three studies achieved the prospectively defined primary
      end-point of a statistically significant reduction in 28-day all-cause mortality.
      The control group mortality rates for these studies were 31%, 43% and 61%,
      indicating that the beneficial effects of adjunct therapies could be demonstrated
      over a wide range of illness severity. Analysis of subgroup data from failed
      studies provided no evidence that the efficacy of the therapeutics being
      investigated varied by baseline placebo mortality rates. Among all studies,
      interventions with anticoagulant activity or anti-inflammatory activity did not
      appear to be harmful in patients with evidence of less coagulopathy or less
      inflammation. CONCLUSION: Our review of published clinical data does not support
      the hypothesis that mortality risk of the population studied alters the relative
      treatment effect associated with anti-inflammatory or other agents used to treat
      severe sepsis. Clinical studies in severe sepsis should continue to enroll
      patients over a wide range of disease severity, as long as patients enrolled have
      evidence of sepsis-induced organ dysfunction(s), patients are at an appreciable
      risk for death (e.g. as evidenced by admission to an intensive care unit), and
      the potential for benefit outweighs the potential for harm.

PMID- 16280059
TI  - Quantifying bedside-derived imaging of microcirculatory abnormalities in septic
      patients: a prospective validation study.
AB  - INTRODUCTION: The introduction of orthogonal polarization spectral (OPS) imaging
      in clinical research has elucidated new perspectives on the role of
      microcirculatory flow abnormalities in the pathogenesis of sepsis. Essential to
      the process of understanding and reproducing these abnormalities is the method of
      quantification of flow scores. METHODS: In a consensus meeting with collaboraters
      from six research centres in different fields of experience with microcirculatory
      OPS imaging, premeditated qualifications for a simple, translucent and
      reproducible way of flow scoring were defined. Consecutively, a single-centre
      prospective observational validation study was performed in a group of 12
      patients with an abdominal sepsis and a new stoma. Flow images of the
      microcirculation in vascular beds of the sublingual and stoma region were
      obtained, processed and analysed in a standardised way. We validated intra
      observer and inter-observer reproducibility with kappa cross-tables for both
      types of microvascular beds. RESULTS: Agreement and kappa coefficients were >85%
      and >0.75, respectively, for interrater and intrarater variability in
      quantification of flow abnormalities during sepsis, in different subsets of
      microvascular architecture. CONCLUSION: Semi-quantitative analysis of
      microcirculatory flow, as described, provides a reproducible and transparent tool
      in clinical research to monitor and evaluate the microcirculation during sepsis.

PMID- 16280060
TI  - Impact of HIV/AIDS on care and outcomes of severe sepsis.
AB  - INTRODUCTION: There has been dramatic improvement in survival for patients with
      HIV/AIDS; however, some studies on patients with HIV/AIDS and serious illness
      have reported continued low rates of intensive care. The purpose of this study
      was to examine patterns of care and outcomes for patients with severe sepsis and
      HIV/AIDS and compare them with those of patients with severe sepsis without
      HIV/AIDS. METHODS: We assessed data from all 1999 discharge abstracts from all
      non-federal hospitals in six US states. Patient demographic characteristics,
      discharge diagnoses, resource use, and outcomes were extracted. Analyses were
      performed using chi-square, Wilcoxon rank sum, or regression techniques, as
      appropriate. RESULTS: We identified 74,020 patients with severe sepsis (7,638
      (10.3%) had HIV/AIDS) using ICD-9-CM codes. Patients with severe sepsis and
      HIV/AIDS had a similar mean length of stay (16.9 days versus 17.7 days; p =
      0.0669), had lower mean hospitalization cost (24,382 dollars versus 30,537
      dollars; p < 0.0001), were less likely to be admitted to the intensive care unit
      (37% versus 56%; p < 0.0001), and had a greater mortality (29% versus 20%; p <
      0.0001) than those without HIV/AIDS. After adjustment for cohort differences,
      patients with severe sepsis and HIV/AIDS had increased likelihood of death (OR
      (95% CI) = 2.41 (2.23-2.61)) and were substantially less likely to be admitted to
      the intensive care unit (OR (95% CI) = 0.54 (0.51-0.59)). When compared with
      those with severe sepsis and HIV/AIDS, patients with severe sepsis without
      HIV/AIDS were universally more likely to be admitted to the intensive care unit,
      even when they had comorbid illnesses with equal or worse expected in-hospital
      mortality (e.g., metastatic cancer). CONCLUSION: For patients with severe sepsis,
      there are differences in care and outcomes for those with HIV/AIDS. Further
      research is needed to examine the delivery of care for patients with severe
      sepsis and HIV/AIDS.

PMID- 16280061
TI  - Early hemoperfusion with an immobilized polymyxin B fiber column eliminates
      humoral mediators and improves pulmonary oxygenation.
AB  - INTRODUCTION: The objective of this study was to clarify the efficacy and
      mechanism of action of direct hemoperfusion with an immobilized polymyxin B fiber
      column (DHP-PMX) in patients with acute lung injury or acute respiratory distress
      syndrome caused by sepsis. METHOD: Thirty-six patients with sepsis were included.
      In each patient a thermodilution catheter was inserted, and the oxygen delivery
      index and oxygen consumption index were measured. DHP-PMX was performed in
      patients with a normal oxygen delivery index and oxygen consumption index (> 500
      ml/minute per m2 and > 120 ml/minute per m2, respectively). The Acute Physiology
      and Chronic Health Evaluation II score was used as an index of the severity of
      sepsis, and survival was assessed after 1 month. The humoral mediators measured
      were the chemokine IL-8, plasminogen activator inhibitor-1, and neutrophil
      elastase (NE). These mediators were measured before DHP-PMX treatment, and at 24,
      48, and 78 hours after the start of treatment. The arterial oxygen tension
      (PaO2)/fractional inspired oxygen (FiO2) ratio was measured before DHP-PMX
      treatment and at 24, 48, 72, 92, and 120 hours after the start of treatment.
      RESULTS: All patients remained alive after 1 month. Before DHP-PMX treatment, the
      Acute Physiology and Chronic Health Evaluation II score was 24 +/- 2.0, the IL-8
      level was 54 +/- 15.8 pg/ml, plasminogen activator inhibitor-1 was 133 +/- 28.1
      ng/ml, and NE was 418 +/- 72.1 mug/l. These three humoral mediators began to
      decrease from 24 hours after DHP-PMX treatment, and the decline became
      significant from 48 hours onward. The PaO2/FiO2 ratio was 244 +/- 26.3 before DHP
      PMX treatment but improved significantly from 96 hours onward. There were
      significant negative correlations between the PaO2/FiO2 ratio and blood levels of
      NE and IL-8. CONCLUSION: The mechanism of action of DHP-PMX is still not fully
      understood, but we report the following findings. The mean blood levels of
      plasminogen activator inhibitor-1, NE, and IL-8 were significantly decreased from
      48 hours after DHP-PMX treatment. The mean PaO2/FiO2 ratio was significantly
      improved from 96 hours after DHP-PMX treatment. Improvement in the PaO2/FiO2
      ratio appeared to be related to the decreases in blood NE and IL-8 levels.

PMID- 16280062
TI  - Elevated troponin and myocardial infarction in the intensive care unit: a
      prospective study.
AB  - INTRODUCTION: Elevated troponin levels indicate myocardial injury but may occur
      in critically ill patients without evidence of myocardial ischemia. An elevated
      troponin alone cannot establish a diagnosis of myocardial infarction (MI), yet
      the optimal methods for diagnosing MI in the intensive care unit (ICU) are not
      established. The study objective was to estimate the frequency of MI using
      troponin T measurements, 12-lead electrocardiograms (ECGs) and echocardiography,
      and to examine the association of elevated troponin and MI with ICU and hospital
      mortality and length of stay. METHOD: In this 2-month single centre prospective
      cohort study, all consecutive patients admitted to our medical-surgical ICU were
      classified in duplicate by two investigators as having MI or no MI based on
      troponin, ECGs and echocardiograms obtained during the ICU stay. The diagnosis of
      MI was based on an adaptation of the joint European Society of
      Cardiology/American College of Cardiology definition: a typical rise or fall of
      an elevated troponin measurement, in addition to ischemic symptoms, ischemic ECG
      changes, a coronary artery intervention, or a new cardiac wall motion
      abnormality. RESULTS: We screened 117 ICU admissions and enrolled 115
      predominantly medical patients. Of these, 93 (80.9%) had at least one ECG and one
      troponin; 44 of these 93 (47.3%) had at least one elevated troponin and 24
      (25.8%) had an MI. Patients with MI had significantly higher mortality in the ICU
      (37.5% versus 17.6%; P = 0.050) and hospital (50.0% versus 22.0%; P = 0.010) than
      those without MI. After adjusting for Acute Physiology and Chronic Health
      Evaluation II score and need for inotropes or vasopressors, MI was an independent
      predictor of hospital mortality (odds ratio 3.22, 95% confidence interval 1.04
      9.96). The presence of an elevated troponin (among those patients in whom
      troponin was measured) was not independently predictive of ICU or hospital
      mortality. CONCLUSION: In this study, 47% of critically ill patients had an
      elevated troponin but only 26% of these met criteria for MI. An elevated troponin
      without ischemic ECG changes was not associated with adverse outcomes; however,
      MI in the ICU setting was an independent predictor of hospital mortality.

PMID- 16280063
TI  - Mortality prediction using SAPS II: an update for French intensive care units.
AB  - INTRODUCTION: The standardized mortality ratio (SMR) is commonly used for
      benchmarking intensive care units (ICUs). Available mortality prediction models
      are outdated and must be adapted to current populations of interest. The
      objective of this study was to improve the Simplified Acute Physiology Score
      (SAPS) II for mortality prediction in ICUs, thereby improving SMR estimates.
      METHOD: A retrospective data base study was conducted in patients hospitalized in
      106 French ICUs between 1 January 1998 and 31 December 1999. A total of 77,490
      evaluable admissions were split into a training set and a validation set.
      Calibration and discrimination were determined for the original SAPS II, a
      customized SAPS II and an expanded SAPS II developed in the training set by
      adding six admission variables: age, sex, length of pre-ICU hospital stay,
      patient location before ICU, clinical category and whether drug overdose was
      present. The training set was used for internal validation and the validation set
      for external validation. RESULTS: With the original SAPS II calibration was poor,
      with marked underestimation of observed mortality, whereas discrimination was
      good (area under the receiver operating characteristic curve 0.858).
      Customization improved calibration but had poor uniformity of fit; discrimination
      was unchanged. The expanded SAPS II exhibited good calibration, good uniformity
      of fit and better discrimination (area under the receiver operating
      characteristic curve 0.879). The SMR in the validation set was 1.007 (confidence
      interval 0.985-1.028). Some ICUs had better and others worse performance with the
      expanded SAPS II than with the customized SAPS II. CONCLUSION: The original SAPS
      II model did not perform sufficiently well to be useful for benchmarking in
      France. Customization improved the statistical qualities of the model but gave
      poor uniformity of fit. Adding simple variables to create an expanded SAPS II
      model led to better calibration, discrimination and uniformity of fit, producing
      a tool suitable for benchmarking.

PMID- 16280064
TI  - Central venous catheter-related infection in a prospective and observational
      study of 2,595 catheters.
AB  - INTRODUCTION: Central venous catheterization is commonly used in critically ill
      patients and may cause different complications, including infection. Although
      there are many studies about CVC-related infection, very few have analyzed it in
      detail. The objective of this study was to analyze the incidence of catheter
      related local infection (CRLI) and catheter-related bloodstream infection (CRBSI)
      with central venous catheters (CVCs) according to different access sites.
      METHODS: This is a prospective and observational study, conducted in a 24-bed
      medical surgical intensive care unit of a 650-bed university hospital. All
      consecutive patients admitted to the ICU during 3 years (1 May 2000 and 30 April
      2003) were included. RESULTS: The study included 2,018 patients. The number of
      CVCs and days of catheterization duration were: global, 2,595 and 18,999;
      subclavian, 917 and 8,239; jugular, 1,390 and 8,361; femoral, 288 and 2,399. CRLI
      incidence density was statistically higher for femoral than for jugular (15.83
      versus 7.65, p < 0.001) and subclavian (15.83 versus 1.57, p < 0.001) accesses,
      and higher for jugular than for subclavian access (7.65 versus 1.57, p < 0.001).
      CRBSI incidence density was statistically higher for femoral than for jugular
      (8.34 versus 2.99, p = 0.002) and subclavian (8.34 versus 0.97, p < 0.001)
      accesses, and higher for jugular than for subclavian access (2.99 versus 0.97, p
      = 0.005). CONCLUSION: Our results suggest that the order for punction, to
      minimize the CVC-related infection risk, should be subclavian (first order),
      jugular (second order) and femoral vein (third order).

PMID- 16280065
TI  - Circulating immune parameters predicting the progression from hospital-acquired
      pneumonia to septic shock in surgical patients.
AB  - INTRODUCTION: Hospital-acquired pneumonia after surgery is one of the major
      causes of septic shock. The excessive inflammatory response appears to be
      responsible for the increased susceptibility to infections and subsequent sepsis.
      The primary aim of this study was to investigate immune parameters at the onset
      of pneumonia, before the development of subsequent septic shock. The secondary
      aim was to investigate the usefulness of these immune parameters in predicting
      progression from hospital-acquired pneumonia to septic shock. METHODS: This
      prospective clinical study included 76 patients with the diagnosis of hospital
      acquired pneumonia. Approval was obtained from the local institutional ethics
      committee and relatives of the patients gave informed consent. Of the 76
      patients, 29 subsequently developed septic shock. All patients were included
      within 4 h of establishing the diagnosis of hospital-acquired pneumonia (first
      collection of blood samples and the analysis of immune mediators). In addition,
      we defined early (within 12 h of onset of septic shock) and late (within 72 to 96
      h of onset) stages of septic shock for the collection of blood samples and the
      analysis of immune mediators. The immune parameters tumor necrosis factor-alpha,
      IL-1beta, IL-6, IL-8 and IL-10 as well as the endothelial leucocyte adhesion
      molecule were analyzed. RESULTS: In the pneumonia group with subsequent septic
      shock, levels of IL-1beta, IL-6, IL-8 and IL-10 were significantly increased
      before the onset of septic shock compared to patients without subsequent septic
      shock. This progression was best predicted by IL-1beta, IL-6, IL-8 and IL-10
      (area under the curve > or = 0.8). CONCLUSION: At the onset of hospital-acquired
      pneumonia, a significant relevant systemic cytokine mediated response had already
      been initiated. It might, therefore, be possible to identify patients at risk for
      septic shock with these predictive markers during early pneumonia. In addition,
      immune modulating therapy might be considered as adjuvant therapy.

PMID- 16280066
TI  - Prognosis for long-term survival and renal recovery in critically ill patients
      with severe acute renal failure: a population-based study.
AB  - INTRODUCTION: Severe acute renal failure (sARF) is associated with considerable
      morbidity, mortality and use of healthcare resources; however, its precise
      epidemiology and long-term outcomes have not been well described in a non
      specified population. METHODS: Population-based surveillance was conducted among
      all adult residents of the Calgary Health Region (population 1 million) admitted
      to multidisciplinary and cardiovascular surgical intensive care units between May
      1 1999 and April 30 2002. Clinical records were reviewed and outcome at 1 year
      was assessed. RESULTS: sARF occurred in 240 patients (11.0 per 100,000
      population/year). Rates were highest in males and older patients (> or = 65 years
      of age). Risk factors for development of sARF included previous heart disease,
      stroke, pulmonary disease, diabetes mellitus, cancer, connective tissue disease,
      chronic renal dysfunction, and alcoholism. The annual mortality rate was 7.3 per
      100,000 population with rates highest in males and those > or = 65 years. The 28
      day, 90-day, and 1-year case-fatality rates were 51%, 60%, and 64%, respectively.
      Increased Charlson co-morbidity index, presence of liver disease, higher APACHE
      II score, septic shock, and need for continuous renal replacement therapy were
      independently associated with death at 1 year. Renal recovery occurred in 78%
      (68/87) of survivors at 1 year. CONCLUSION: sARF is common and males, older
      patients, and those with underlying medical conditions are at greatest risk.
      Although the majority of patients with sARF will die, most survivors will become
      independent from renal replacement therapy within a year.

PMID- 16280067
TI  - Surfactant application during extracorporeal membrane oxygenation improves lung
      volume and pulmonary mechanics in children with respiratory failure.
AB  - INTRODUCTION: This study was performed to determine whether surfactant
      application during extracorporeal membrane oxygenation (ECMO) improves lung
      volume, pulmonary mechanics, and chest radiographic findings in children with
      respiratory failure or after cardiac surgery. METHODS: This was a retrospective
      chart review study in a pediatric intensive care unit (PICU). Seven patients
      received surfactant before weaning from ECMO was started (group S). They were
      compared to six patients treated with ECMO who did not receive surfactant (group
      C). These control patients were matched based on age, weight, and underlying
      diagnosis. Demographic data, ventilator settings, tidal volume, compliance of
      respiratory system (calculated from tidal volume/(peak inspiratory pressure -
      positive end-expiratory pressure), and ECMO flow were extracted. Chest
      radiographs were scored by two blinded and independent radiologists. Changes over
      time were compared between groups by repeated-measures analysis of variance
      (time*group interaction). Values are given as percentages of baseline values.
      RESULTS: The groups did not differ with regard to demographic data, duration of
      ECMO, ventilator settings, PICU and hospital days. After application of
      surfactant, mean tidal volume almost doubled in group S (from 100% before to
      186.2%; p = 0.0053). No change was found in group C (100% versus 98.7%). Mean
      compliance increased significantly (p = 0.0067) in group S (from 100% to 176.1%)
      compared to group C (100% versus 97.6%). Radiographic scores tended to decrease
      in group S within 48 h following surfactant application. ECMO flow tended to
      decrease in group S within 10 h following surfactant application but not in group
      C. Mortality was not affected by treatment. CONCLUSION: Surfactant application
      may be of benefit in children with respiratory failure treated with ECMO, but
      these findings need confirmation from prospective studies.

PMID- 16280068
TI  - Tezosentan reduces the microvascular filtration coefficient in isolated lungs
      from rats subjected to cecum ligation and puncture.
AB  - INTRODUCTION: We recently demonstrated that the non-selective endothelin-1 (ET-1)
      receptor blocker tezosentan antagonizes ovine acute lung injury (ALI) following
      infusion of endotoxin or ET-1 by reducing the enhanced lung microvascular
      pressure, although we could not exclude the possibility of a simultaneous decline
      in microvascular permeability. In the present study, our aim was to find out if
      tezosentan reverses the rise in microvascular filtration coefficient (Kfc) in rat
      lungs that have been isolated and perfused 12 h after cecum ligation and puncture
      (CLP) or infusion of ET-1. METHODS: Wistar rats (n = 42) were subjected to CLP.
      Postoperatively, rats were randomized to a CLP group (n = 7) and a CLP +
      tezosentan group (n = 7); the latter received tezosentan 30 mg/kg. A sham
      operated group (n = 5) underwent laparotomy without CLP. Twelve hours
      postoperatively, the lungs were isolated and perfused with blood from similarly
      treated rats that also were used to assess plasma concentration of ET-1 and
      protein kinase Calpha (PKCalpha) in lung tissue. Additionally, isolated blood
      perfused lungs from healthy rats were randomized to a control group (n = 8), an
      ET-1 group (n = 7) subjected to pulmonary arterial injection of ET-1 10 nM, and
      an ET-1 + tezosentan group (n = 7) that received tezosentan 30 mg/kg. All lung
      preparations received papaverine 0.1 microg/kg added to the perfusate for
      vasoplegia. Pulmonary hemodynamic variables, Kfc and lung compliance (CL) were
      assessed. RESULTS: After CLP, the plasma concentration of ET-1 increased.
      Papaverine abolished the vasoconstrictor response to ET-1 and the pulmonary
      vascular pressures remained close to baseline throughout the experiments. Both
      CLP and injection of ET-1 caused significant changes in Kfc and CL that were
      prevented in tezosentan-treated rats. Compared to sham-operated animals, CLP
      increased the content of PKCalpha by 50% and 70% in the cytosolic and the
      membrane fractions of lung tissue homogenates, respectively. Tezosentan prevented
      the upregulation of PKCalpha in the membrane fraction. CONCLUSION: In rat lungs
      isolated and perfused after CLP, tezosentan precludes both the increase in Kfc
      and the upregulation of PKCalpha in the membrane fraction of lung tissue.

PMID- 16280069
TI  - The use of prophylactic fluconazole in immunocompetent high-risk surgical
      patients: a meta-analysis.
AB  - INTRODUCTION: High-risk surgical patients are at increased risk of fungal
      infections and candidaemia. Evidence from observational and small randomised
      controlled studies suggests that prophylactic fluconazole may be effective in
      reducing fungal infection and mortality. We evaluated the effects of prophylactic
      fluconazole on the incidence of candidaemia and hospital mortality in
      immunocompetent high-risk surgical patients. METHODS: Randomised controlled
      studies involving the use of fluconazole in immunocompetent high-risk surgical
      patients from the Cochrane Controlled Trial Register (2005, issue 1) and from the
      EMBASE and MEDLINE databases (1966-30 April 2005), without any language
      restriction, were included. Two reviewers reviewed the quality of the studies and
      performed data extraction independently. RESULTS: Seven randomised controlled
      studies with a total of 814 immunocompetent high-risk surgical patients were
      considered. The use of prophylactic fluconazole was associated with a reduction
      in the proportion of patients with candidaemia (relative risk [RR] = 0.21, 95%
      confidence interval [CI] = 0.06-0.72, P = 0.01; I2 = 0%) and fungal infections
      other than lower urinary tract infection (RR = 0.39, 95% CI = 0.24-0.65, P =
      0.0003; I2 = 0%), but was associated with only a trend towards a reduction in
      hospital mortality (RR = 0.82, 95% CI = 0.62-1.08, P = 0.15; I2 = 7%). The
      proportion of patients requiring systemic amphotericin B as a rescue therapy for
      systemic fungal infection was lower after prophylactic use of fluconazole (RR =
      0.35, 95% CI = 0.17-0.72, P = 0.004; I2 = 0%). The proportion of patients
      colonised with or infected with fluconazole-resistant fungi was not significantly
      different between the fluconazole group and the placebo group (RR = 0.66, 95% CI
      = 0.22-1.96, P = 0.46; I2 = 0%). CONCLUSION: The use of prophylactic fluconazole
      in immunocompetent high-risk surgical patients is associated with a reduced
      incidence of candidaemia but with only a trend towards a reduction in hospital
      mortality.

PMID- 16280070
TI  - Prolonged refractory status epilepticus following acute traumatic brain injury: a
      case report of excellent neurological recovery.
AB  - INTRODUCTION: Refractory status epilepticus (RSE) secondary to traumatic brain
      injury (TBI) may be under-recognized and is associated with significant morbidity
      and mortality. METHODS: This case report describes a 20 year old previously
      healthy woman who suffered a severe TBI as a result of a motor vehicle collision
      and subsequently developed RSE. Pharmacological coma, physiological support and
      continuous electroencephalography (cEEG) were undertaken. RESULTS: Following 25
      days of pharmacological coma, electrographic and clinical seizures subsided and
      the patient has made an excellent cognitive recovery. CONCLUSION: With early
      identification, aggressive physiological support, appropriate monitoring,
      including cEEG, and an adequate length of treatment, young trauma patients with
      no previous seizure history and limited structural damage to the brain can have
      excellent neurological recovery from prolonged RSE.

PMID- 16280072
TI  - Mixed protocols: multiple ratios of FSH and LH bioactivity using highly purified,
      human-derived FSH (BRAVELLE) and highly purified hMG (MENOPUR) are unaltered by
      mixing together in the same syringe.
AB  - BACKGROUND: The use of mixed or blended protocols, that utilize both FSH and hMG,
      for controlled ovarian hyperstimulation is increasing in use. To reduce the
      number of injections a patient must administer, many physicians instruct their
      patients to mix their FSH and hMG together to be given as a single injection.
      Therefore, the goal of this study was to definitively determine if the FSH and LH
      bioactivities of highly purified, human-derived FSH (Bravelle) and highly
      purified hMG (Menopur) were altered by reconstituting in 0.9% saline and mixing
      in the same syringe. METHODS: Bravelle and Menopur were reconstituted in 0.9%
      saline and mixed in a Becton Dickinson plastic syringe. The FSH and LH
      bioactivities of the products were determined after injecting female and male
      rats, respectively, with Bravelle, Menopur, or a mixture of Bravelle and Menopur.
      Ratios of FSH:LH activity tested were 150:75 IU (1 vial Bravelle: 1 vial
      Menopur), 300:75 IU (3 vials Bravelle: 1 vial Menopur) or 300:225 IU (1 vial
      Bravelle: 3 vials of Menopur). RESULTS: There were no statistically significant
      changes in either FSH or LH bioactivity that occurred after mixing Bravelle with
      Menopur in the same syringe. The theoretical vs. actual FSH bioactivity for
      Bravelle and Menopur were 75 vs. 76.58 IU/mL and 75 vs. 76.0 IU/mL, respectively.
      For the 3 ratios of FSH:LH activity tested, 150:75 IU (1 vial Bravelle: 1 vial
      Menopur), 300:75 IU (3 vials Bravelle: 1 vial Menopur) or 300:225 IU (1 vial
      Bravelle: 3 vials of Menopur) tested, the theoretical vs. actual FSH
      bioactivities were 150 vs. 156.86 IU/mL, 300 vs. 308.69 IU/mL and 300 vs. 306.58
      IU/mL, respectively. The theoretical vs. actual LH bioactivity for Menopur in the
      above mentioned ratios tested were 75 vs. 77.50 IU/mL. For the 3 ratios of FSH:LH
      activity tested, 150:75 IU (1 vial Bravelle: 1 vial Menopur), 300:75 IU (3 vials
      Bravelle: 1 vial Menopur) or 300:225 IU (1 vial Bravelle: 3 vials of Menopur),
      the theoretical vs. actual LH bioactivities were 75 vs. 78.38 IU/mL, 75 vs. 78.63
      IU/mL and 225 vs. 233.48 IU/mL, respectively. CONCLUSION: Mixing human-derived
      FSH (Bravelle) with highly purified hMG (Menopur) in the same diluent, 0.9% NaCL,
      does not alter the FSH or LH bioactivity of either gonadotropin preparation.

PMID- 16280073
TI  - Subcutaneously administered Menopur, a new highly purified human menopausal
      gonadotropin, causes significantly fewer injection site reactions than Repronex
      in subjects undergoing in vitro fertilization.
AB  - BACKGROUND: The safety and tolerability of a new highly purified, urine-derived
      human menopausal gonadotropin (hMG) preparation [Menopur] was compared with a
      currently available hMG [Repronex] in women undergoing in vitro fertilization
      (IVF). METHODS: This was a randomized, open-label, parallel-group, multicenter
      study conducted in subjects undergoing IVF. Women (N = 125), 18-39 years of age,
      underwent pituitary down-regulation with leuprolide acetate beginning 7 days
      prior to onset of menses and continuing up to the day before hCG administration.
      Subjects were randomized to receive subcutaneous (SC) Menopur (n = 61) or
      Repronex SC (n = 64) for a maximum of 12 days. All adverse events (AEs) were
      recorded and subject self-assessments of injection site reactions were recorded
      in a daily diary. RESULTS: Significantly fewer subjects in the Menopur group
      reported injection site reactions (P < 0.001) compared to the Repronex group.
      Overall, there was no statistically significant difference in the incidence of
      AEs between the two treatment groups. CONCLUSION: Menopur SC offers a greater
      safety and tolerability profile compared to Repronex SC.

PMID- 16280074
TI  - Postoperative mortality after cancer surgery in octogenarians and nonagenarians:
      results from a series of 5,390 patients.
AB  - BACKGROUND: To support decisions about surgical treatment of elderly patients
      with cancer, population-based estimates of postoperative mortality (POM) rates
      are required. METHODS: Electronic records from the Rotterdam Cancer Registry were
      retrieved for octogenarians and nonagenarians who underwent resection in the
      period 1987-2000. POM was defined as death within 30 days of resection and both
      elective and emergency operations were included. RESULTS: In a series of 5.390
      operated patients aged 80 years and older, POM rates were 0.5% for breast cancer,
      1.7% for endometrial cancer and 4.2% for renal cancer. For patients with
      colorectal cancer, POM increased from 8% for the age group 80-84 to 13% for those
      85-89 to 20% in nonagenarians. For stomach cancer, the respective figures were
      11%, 20% and 44%. CONCLUSION: These results show that resections can be performed
      at acceptable risk in selected elderly patients with cancer.

PMID- 16280075
TI  - Fertility in four regions spanning large contrasts in serum levels of widespread
      persistent organochlorines: a cross-sectional study.
AB  - BACKGROUND: Persistent organochlorine pollutants (POPs) may interfere with
      reproductive function but direct evidence in humans is very limited. METHODS:
      Fertility was examined in four regions with contrasting blood levels of POPs.
      Pregnant women and their partners in Warsaw (Poland), Kharkiv (Ukraine) and
      Greenland were consecutively enrolled during antenatal visits. Swedish fishermen
      and their spouses were recruited separately and independently of current
      pregnancy. Lipid adjusted serum concentrations of 2,2',4,4',5,5'
      hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene
      (DDE) were available for both partners. Time to pregnancy interviews were
      obtained among 2269 women and 798 men provided a semen sample. RESULTS: Inuits
      had high levels of both POP markers, Swedish fishermen were high in CB-153 but
      low in DDE, men from Kharkiv were high in DDE and low in CB-153 while men from
      Warsaw were low in CB-153 and had intermediate DDE levels. Compared to Warsaw
      couples, fecundability was reduced among couples from Kharkiv [adjusted
      fecundability ratio (FR) 0.64 (95% CI 0.5-0.8)] and elevated in Swedish fishermen
      families [FR 1.26 (95% CI 1.0-1.6)]. Adjusted geometric means of sperm counts and
      morphology did not differ between regions while sperm motility was higher in men
      living in Warsaw. CONCLUSION: We observed regional differences in time to
      pregnancy and sperm motility that may be related to regional differences in POP
      blood levels, but other interpretations are also plausible. In particular,
      differences in access to safe contraception and in the prevalence of
      contraceptive failures are most likely to bias comparisons of time to pregnancy.

PMID- 16280077
TI  - The Swiss cheese model of safety incidents: are there holes in the metaphor?
AB  - BACKGROUND: Reason's Swiss cheese model has become the dominant paradigm for
      analysing medical errors and patient safety incidents. The aim of this study was
      to determine if the components of the model are understood in the same way by
      quality and safety professionals. METHODS: Survey of a volunteer sample of
      persons who claimed familiarity with the model, recruited at a conference on
      quality in health care, and on the internet through quality-related websites. The
      questionnaire proposed several interpretations of components of the Swiss cheese
      model: a) slice of cheese, b) hole, c) arrow, d) active error, e) how to make the
      system safer. Eleven interpretations were compatible with this author's
      interpretation of the model, 12 were not. RESULTS: Eighty five respondents stated
      that they were very or quite familiar with the model. They gave on average 15.3
      (SD 2.3, range 10 to 21) "correct" answers out of 23 (66.5%)--significantly more
      than 11.5 "correct" answers that would expected by chance (p < 0.001).
      Respondents gave on average 2.4 "correct" answers regarding the slice of cheese
      (out of 4), 2.7 "correct" answers about holes (out of 5), 2.8 "correct" answers
      about the arrow (out of 4), 3.3 "correct" answers about the active error (out of
      5), and 4.1 "correct" answers about improving safety (out of 5). CONCLUSION: The
      interpretations of specific features of the Swiss cheese model varied
      considerably among quality and safety professionals. Reaching consensus about
      concepts of patient safety requires further work.

PMID- 16280078
TI  - MiMiR: a comprehensive solution for storage, annotation and exchange of
      microarray data.
AB  - BACKGROUND: The generation of large amounts of microarray data presents
      challenges for data collection, annotation, exchange and analysis. Although there
      are now widely accepted formats, minimum standards for data content and
      ontologies for microarray data, only a few groups are using them together to
      build and populate large-scale databases. Structured environments for data
      management are crucial for making full use of these data. DESCRIPTION: The MiMiR
      database provides a comprehensive infrastructure for microarray data annotation,
      storage and exchange and is based on the MAGE format. MiMiR is MIAME-supportive,
      customised for use with data generated on the Affymetrix platform and includes a
      tool for data annotation using ontologies. Detailed information on the
      experiment, methods, reagents and signal intensity data can be captured in a
      systematic format. Reports screens permit the user to query the database, to view
      annotation on individual experiments and provide summary statistics. MiMiR has
      tools for automatic upload of the data from the microarray scanner and export to
      databases using MAGE-ML. CONCLUSION: MiMiR facilitates microarray data
      management, annotation and exchange, in line with international guidelines. The
      database is valuable for underpinning research activities and promotes a
      systematic approach to data handling. Copies of MiMiR are freely available to
      academic groups under licence.

PMID- 16280079
TI  - Prevalence of mental disorders and torture among Tibetan refugees: a systematic
      review.
AB  - BACKGROUND: Many Tibetan refugees flee Tibet in order to escape physical and
      mental hardships, and to access the freedoms to practice their culture and
      religion. We aimed to determine the prevalence of mental illnesses within the
      refugee population and determine the prevalence of previous torture reported
      within this population. METHODS: We performed a systematic literature search of
      10 electronic databases from inception to May 2005. In addition, we searched the
      internet, contacted all authors of located studies, and contacted the Tibetan
      Government-in-exile, to locate unpublished studies. We included any study
      reporting on prevalence of mental illness within the Tibetan refugee populations.
      We determined study quality according to validation, translation, and interview
      administration. We calculated proportions with exact confidence intervals.
      RESULTS: Five studies that met our inclusion criteria (total n = 410). All
      studies were conducted in North India and 4 were specifically in adult
      populations. Four studies provided details on the prevalence of torture and
      previous imprisonment within the populations. The prevalence of post-traumatic
      stress disorder ranged from 11-23%, anxiety ranged from 25-77%, and major
      depression ranged from 11.5-57%. CONCLUSION: Our review indicates that the
      prevalence of serious mental health disorders within this population is elevated.
      The reported incidence of torture and imprisonment is a possible contributor to
      the illnesses. Non-government organizations and international communities should
      be aware of the human rights abuses being levied upon this vulnerable population
      and the mental health outcomes that may be associated with it.

PMID- 16280076
TI  - Tat gets the "green" light on transcription initiation.
AB  - Human immunodeficiency virus type 1 (HIV-1) Tat transactivation is an essential
      step in the viral life cycle. Over the past several years, it has become widely
      accepted that Tat exerts its transcriptional effect by binding the
      transactivation-responsive region (TAR) and enhancing transcriptional elongation.
      Consistent with this hypothesis, it has been shown that Tat promotes the binding
      of P-TEFb, a transcription elongation factor composed of cyclin T1 and cdk9, and
      the interaction of Tat with P-TEFb and TAR leads to hyperphosphorylation of the C
      terminal domain (CTD) of RNA Pol II and increased processivity of RNA Pol II. A
      recent report, however, has generated renewed interest that Tat may also play a
      critical role in transcription complex (TC) assembly at the preinitiation step.
      Using in vivo chromatin immunoprecipitation assays, the authors reported that the
      HIV TC contains TBP but not TBP-associated factors. The stimulatory effect
      involved the direct interaction of Tat and P-TEFb and was evident at the earliest
      step of TC assembly, the TBP-TATA box interaction. In this article, we will
      review this data in context of earlier data which also support Tat's involvement
      in transcriptional complex assembly. Specifically, we will discuss experiments
      which demonstrated that Tat interacted with TBP and increased transcription
      initiation complex stability in cell free assays. We will also discuss studies
      which demonstrated that over expression of TBP alone was sufficient to obtain Tat
      activated transcription in vitro and in vivo. Finally, studies using self
      cleaving ribozymes which suggested that Tat transactivation was not compatible
      with pausing of the RNA Pol II at the TAR site will be discussed.

PMID- 16280080
TI  - Actuarial survival of a large Canadian cohort of preterm infants.
AB  - BACKGROUND: The increased survival of preterm and very low birth weight infants
      in recent years has been well documented but continued surveillance is required
      in order to monitor the effects of new therapeutic interventions. Gestation and
      birth weight specific survival rates most accurately reflect the outcome of
      perinatal care. Our aims were to determine survival to discharge for a large
      Canadian cohort of preterm infants admitted to the neonatal intensive care unit
      (NICU), and to examine the effect of gender on survival and the effect of
      increasing postnatal age on predicted survival. METHODS: Outcomes for all 19,507
      infants admitted to 17 NICUs throughout Canada between January 1996 and October
      1997 were collected prospectively. Babies with congenital anomalies were excluded
      from the study population. Gestation and birth weight specific survival for all
      infants with birth weight < 1,500 g (n = 3419) or gestation < or = 30 weeks (n =
      3119) were recorded. Actuarial survival curves were constructed to show changes
      in expected survival with increasing postnatal age. RESULTS: Survival to
      discharge at 24 weeks gestation was 54%, compared to 82% at 26 weeks and 95% at
      30 weeks. In infants with birth weights 600-699, survival to discharge was 62%,
      compared to 79% at 700-799 g and 96% at 1,000-1,099 g. In infants born at 24
      weeks gestational age, survival was higher in females but there were no
      significant gender differences above 24 weeks gestation. Actuarial analysis
      showed that risk of death was highest in the first 5 days. For infants born at 24
      weeks gestation, estimated survival probability to 48 hours, 7 days and 4 weeks
      were 88 (CI 84, 92)%, 70 (CI 64, 76)% and 60 (CI 53, 66)% respectively. For
      smaller birth weights, female survival probabilities were higher than males for
      the first 40 days of life. CONCLUSION: Actuarial analysis provides useful
      information when counseling parents and highlights the importance of frequently
      revising the prediction for long term survival particularly after the first few
      days of life.

PMID- 16280081
TI  - Exploration of phylogenetic data using a global sequence analysis method.
AB  - BACKGROUND: Molecular phylogenetic methods are based on alignments of nucleic or
      peptidic sequences. The tremendous increase in molecular data permits
      phylogenetic analyses of very long sequences and of many species, but also
      requires methods to help manage large datasets. RESULTS: Here we explore the
      phylogenetic signal present in molecular data by genomic signatures, defined as
      the set of frequencies of short oligonucleotides present in DNA sequences.
      Although violating many of the standard assumptions of traditional phylogenetic
      analyses--in particular explicit statements of homology inherent in character
      matrices--the use of the signature does permit the analysis of very long
      sequences, even those that are unalignable, and is therefore most useful in cases
      where alignment is questionable. We compare the results obtained by traditional
      phylogenetic methods to those inferred by the signature method for two genes:
      RAG1, which is easily alignable, and 18S RNA, where alignments are often
      ambiguous for some regions. We also apply this method to a multigene data set of
      33 genes for 9 bacteria and one archea species as well as to the whole genome of
      a set of 16 gamma-proteobacteria. In addition to delivering phylogenetic results
      comparable to traditional methods, the comparison of signatures for the sequences
      involved in the bacterial example identified putative candidates for horizontal
      gene transfers. CONCLUSION: The signature method is therefore a fast tool for
      exploring phylogenetic data, providing not only a pretreatment for discovering
      new sequence relationships, but also for identifying cases of sequence evolution
      that could confound traditional phylogenetic analysis.

PMID- 16280082
TI  - Specific and sensitive detection of the conifer pathogen Gremmeniella abietina by
      nested PCR.
AB  - BACKGROUND: Gremmeniella abietina (Lagerb.) Morelet is an ascomycete fungus that
      causes stem canker and shoot dieback in many conifer species. The fungus is
      widespread and causes severe damage to forest plantations in Europe, North
      America and Asia. To facilitate early diagnosis and improve measures to control
      the spread of the disease, rapid, specific and sensitive detection methods for G.
      abietina in conifer hosts are needed. RESULTS: We designed two pairs of specific
      primers for G. abietina based on the 18S rDNA sequence variation pattern. These
      primers were validated against a wide range of fungi and 14 potential conifer
      hosts. Based on these specific primers, two nested PCR systems were developed.
      The first system employed universal fungal primers to enrich the fungal DNA
      targets in the first round, followed by a second round selective amplification of
      the pathogen. The other system employed G. abietina-specific primers in both PCR
      steps. Both approaches can detect the presence of G. abietina in composite
      samples with high sensitivity, as little as 7.5 fg G. abietina DNA in the host
      genomic background. CONCLUSION: The methods described here are rapid and can be
      applied directly to a wide range of conifer species, without the need for fungal
      isolation and cultivation. Therefore, it represents a promising alternative to
      disease inspection in forest nurseries, plantations and quarantine control
      facilities.

PMID- 16280083
TI  - Using genomic DNA-based probe-selection to improve the sensitivity of high
      density oligonucleotide arrays when applied to heterologous species.
AB  - High-density oligonucleotide (oligo) arrays are a powerful tool for transcript
      profiling. Arrays based on GeneChip technology are amongst the most widely used,
      although GeneChip arrays are currently available for only a small number of plant
      and animal species. Thus, we have developed a method to improve the sensitivity
      of high-density oligonucleotide arrays when applied to heterologous species and
      tested the method by analysing the transcriptome of Brassica oleracea L., a
      species for which no GeneChip array is available, using a GeneChip array designed
      for Arabidopsis thaliana (L.) Heynh. Genomic DNA from B. oleracea was labelled
      and hybridised to the ATH1-121501 GeneChip array. Arabidopsis thaliana probe
      pairs that hybridised to the B. oleracea genomic DNA on the basis of the perfect
      match (PM) probe signal were then selected for subsequent B. oleracea
      transcriptome analysis using a .cel file parser script to generate probe mask
      files. The transcriptional response of B. oleracea to a mineral nutrient
      (phosphorus; P) stress was quantified using probe mask files generated for a wide
      range of gDNA hybridisation intensity thresholds. An example probe mask file
      generated with a gDNA hybridisation intensity threshold of 400 removed > 68 % of
      the available PM probes from the analysis but retained >96 % of available A.
      thaliana probe-sets. Ninety-nine of these genes were then identified as
      significantly regulated under P stress in B. oleracea, including the homologues
      of P stress responsive genes in A. thaliana. Increasing the gDNA hybridisation
      intensity thresholds up to 500 for probe-selection increased the sensitivity of
      the GeneChip array to detect regulation of gene expression in B. oleracea under P
      stress by up to 13-fold. Our open-source software to create probe mask files is
      freely available http://affymetrix.arabidopsis.info/xspecies/ and may be used to
      facilitate transcriptomic analyses of a wide range of plant and animal species in
      the absence of custom arrays.

PMID- 16280084
TI  - ErmineJ: tool for functional analysis of gene expression data sets.
AB  - BACKGROUND: It is common for the results of a microarray study to be analyzed in
      the context of biologically-motivated groups of genes such as pathways or Gene
      Ontology categories. The most common method for such analysis uses the
      hypergeometric distribution (or a related technique) to look for "over
      representation" of groups among genes selected as being differentially expressed
      or otherwise of interest based on a gene-by-gene analysis. However, this method
      suffers from some limitations, and biologist-friendly tools that implement
      alternatives have not been reported. RESULTS: We introduce ErmineJ, a
      multiplatform user-friendly stand-alone software tool for the analysis of
      functionally-relevant sets of genes in the context of microarray gene expression
      data. ErmineJ implements multiple algorithms for gene set analysis, including
      over-representation and resampling-based methods that focus on gene scores or
      correlation of gene expression profiles. In addition to a graphical user
      interface, ErmineJ has a command line interface and an application programming
      interface that can be used to automate analyses. The graphical user interface
      includes tools for creating and modifying gene sets, visualizing the Gene
      Ontology as a table or tree, and visualizing gene expression data. ErmineJ comes
      with a complete user manual, and is open-source software licensed under the Gnu
      Public License. CONCLUSION: The availability of multiple analysis algorithms,
      together with a rich feature set and simple graphical interface, should make
      ErmineJ a useful addition to the biologist's informatics toolbox. ErmineJ is
      available from http://microarray.cu.genome.org.

PMID- 16280086
TI  - Co-occurrence of autoimmune thyroid disease in a multiple sclerosis cohort.
AB  - BACKGROUND: Multiple sclerosis (MS), Hashimoto's disease and Graves' disease are
      autoimmune diseases that may share similar pathogenic mechanisms. The co
      occurrence rates and demographic characteristics of Graves' disease and
      Hashimoto's disease (HT) in our MS population are compared with the general
      population. METHODS: The prevalence of thyroid disease in our MS patients was
      determined by chart review and survey. Previous diagnosis of thyroid disease, age
      at diagnosis, treatment used, and about the use of disease modifying medications
      used to treat their MS were asked. Chart reviews were used to estimate the
      population prevalence of Graves' disease and Hashimoto's disease and to estimate
      the demographics of patients with thyroid disease. RESULTS: A significant co
      occurrence of Graves' disease with MS (p = 0.002), and a non-significant co
      occurrence of Hashimoto's disease were noted (p = 0.097). No difference in the
      age of onset or gender of thyroid disease in MS patients compared to the general
      population was found. CONCLUSION: There is a significant co-occurrence in
      patients with MS and Graves' disease, and a trend to co-occurrence in patients
      with MS and Hashimoto's disease. There are no differences in the demographics of
      patients with thyroid disease in our MS patients compared to the general
      population.

PMID- 16280087
TI  - A qualitative study of nursing student experiences of clinical practice.
AB  - BACKGROUND: Nursing student's experiences of their clinical practice provide
      greater insight to develop an effective clinical teaching strategy in nursing
      education. The main objective of this study was to investigate student nurses'
      experience about their clinical practice. METHODS: Focus groups were used to
      obtain students' opinion and experiences about their clinical practice. 90
      baccalaureate nursing students at Shiraz University of Medical Sciences (Faculty
      of Nursing and Midwifery) were selected randomly from two hundred students and
      were arranged in 9 groups of ten students. To analyze the data the method used to
      code and categories focus group data were adapted from approaches to qualitative
      data analysis. RESULTS: Four themes emerged from the focus group data. From the
      students' point of view," initial clinical anxiety", "theory-practice gap","
      clinical supervision", professional role", were considered as important factors
      in clinical experience. CONCLUSION: The result of this study showed that nursing
      students were not satisfied with the clinical component of their education. They
      experienced anxiety as a result of feeling incompetent and lack of professional
      nursing skills and knowledge to take care of various patients in the clinical
      setting.

PMID- 16280085
TI  - Genetic mapping of putative Chrna7 and Luzp2 neuronal transcriptional enhancers
      due to impact of a transgene-insertion and 6.8 Mb deletion in a mouse model of
      Prader-Willi and Angelman syndromes.
AB  - BACKGROUND: Prader-Willi and Angelman syndrome (PWS and AS) patients typically
      have an approximately 5 Mb deletion of human chromosome 15q11-q13, of opposite
      parental origin. A mouse model of PWS and AS has a transgenic insertion-deletion
      (TgPWS/TgAS) of chromosome 7B/C subsequent to paternal or maternal inheritance,
      respectively. In this study, we define the deletion endpoints and examine the
      impact on expression of flanking genes. RESULTS: Using molecular and cytological
      methods we demonstrate that 13 imprinted and 11 non-imprinted genes are included
      in the TgPWS/TgAS deletion. Normal expression levels were found in TgPWS brain
      for genes extending 9.1- or 5.6-Mb centromeric or telomeric of the deletion,
      respectively. Our molecular cytological studies map the proximal deletion
      breakpoint between the Luzp2 and Siglec-H loci, and we show that overall mRNA
      levels of Luzp2 in TgPWS and TgAS brain are significantly reduced by 17%.
      Intriguingly, 5' Chrna7 shows 1.7-fold decreased levels in TgPWS and TgAS brain
      whereas there is a > or =15-fold increase in expression in neonatal liver and
      spleen of these mouse models. By isolating a Chrna7-Tg fusion transcript from
      TgAS mice, we mapped the telomeric deletion breakpoint in Chrna7 intron 4.
      CONCLUSION: Based on the extent of the deletion, TgPWS/TgAS mice are models for
      PWS/AS class I deletions. Other than for the first gene promoters immediately
      outside the deletion, since genes extending 5.6-9.1 Mb away from each end of the
      deletion show normal expression levels in TgPWS brain, this indicates that the
      transgene array does not induce silencing and there are no additional linked
      rearrangements. Using gene expression, non-coding conserved sequence (NCCS) and
      synteny data, we have genetically mapped a putative Luzp2 neuronal enhancer
      responsible for approximately 33% of allelic transcriptional activity. The Chrna7
      results are explained by hypothesizing loss of an essential neuronal
      transcriptional enhancer required for approximately 80% of allelic Chrna7
      promoter activity, while the Chrna7 promoter is upregulated in B lymphocytes by
      the transgene immunoglobulin enhancer. The mapping of a putative Chrna7 neuronal
      enhancer inside the deletion has significant implications for understanding the
      transcriptional regulation of this schizophrenia-susceptibility candidate gene.

PMID- 16280088
TI  - Experiences in applying skills learned in a Mental Health First Aid training
      course: a qualitative study of participants' stories.
AB  - BACKGROUND: Given the high prevalence of mental disorders and the comparatively
      low rate of professional help-seeking, it is useful for members of the public to
      have some skills in how to assist people developing mental disorders. A Mental
      Health First Aid course has been developed to provide these skills. Two
      randomized controlled trials of this course have shown positive effects on
      participants' knowledge, attitudes and behavior. However, these trials have
      provided limited data on participants' subsequent experiences in providing first
      aid. To remedy this, a study was carried out gathering stories from participants
      in one of the trials, 19-21 months post-training. METHODS: Former course
      participants were contacted and sent a questionnaire either by post or via the
      internet. Responses were received from 94 out of the 131 trainees who were
      contacted. The questionnaire asked about whether the participant had experienced
      a post-training situation where someone appeared to have a mental health problem
      and, if so, asked questions about that experience. RESULTS: Post-training
      experiences were reported by 78% of respondents. Five key points emerged from the
      qualitative data: (1) the majority of respondents had had some direct experience
      of a situation where mental health issues were salient and the course enabled
      them to take steps that led to better effects than otherwise might have been the
      case; (2) positive effects were experienced in terms of increased empathy and
      confidence, as well as being better able to handle crises; (3) the positive
      effects were experienced by a wide range of people with varied expectations and
      needs; (4) there was no evidence of people over-reaching themselves because of
      over-confidence and (5) those who attended were able to identify quite specific
      benefits and many thought the course not only very useful, but were keen to see
      it repeated and extended. CONCLUSION: The qualitative data confirm that most
      members of the public who receive Mental Health First Aid training subsequently
      provide support to people with mental health problems and that this support
      generally has positive effects.

PMID- 16280089
TI  - Manipulative therapy and/or NSAIDs for acute low back pain: design of a
      randomized controlled trial [ACTRN012605000036617].
AB  - BACKGROUND: Acute low back pain is a common condition resulting in pain and
      disability. Current national and international guidelines advocate general
      practitioner care including advice and paracetamol (4 g daily in otherwise well
      adults) as the first line of care for people with acute low back pain. Non
      steroidal anti-inflammatory drugs (NSAIDs) and spinal manipulative therapy (SMT)
      are advocated in many guidelines as second line management options for patients
      with acute low back pain who are not recovering. No studies have explored the
      role of NSAIDs and/or SMT in addition to first line management for acute low back
      pain. The primary aim of this study is to investigate if NSAIDs and/or SMT in
      addition to general practitioner advice and paracetamol results in shorter
      recovery times for patients with acute low back pain. The secondary aims of the
      study are to evaluate whether the addition of SMT and/or NSAIDs influences pain,
      disability and global perceived effect at 1, 2, 4 and 12 weeks after onset of
      therapy for patients with significant acute low back pain. METHODS/DESIGN: This
      paper presents the rationale and design of a randomised controlled trial
      examining the addition of NSAIDs and/or SMT in 240 people who present to their
      general practitioner with significant acute low back pain.

PMID- 16280090
TI  - Regional variation in hospitalization for stroke among Asians/Pacific Islanders
      in the United States: a nationwide retrospective cohort study.
AB  - BACKGROUND: In Asia, stroke incidence varies dramatically from country to
      country. Little is known about stroke incidence in Asians/Pacific Islanders in
      the US, where regional heterogeneity in Asian/Pacific Islander sub-populations is
      great. We sought to characterize both the national and regional incidences of
      first and recurrent hospitalized acute ischemic stroke, subarachnoid hemorrhage,
      and intracerebral hemorrhage in Asians/Pacific Islanders compared to non-Hispanic
      whites. METHODS: We used the National Inpatient Sample of the 1997 Healthcare
      Cost and Utilization Project. It is a 20% stratified sample of hospitalizations
      to nonfederal hospitals in the US. National and regional projections were made
      using sampling weights specific for patients and hospitals. We identified stroke
      subtypes using previously validated ICD-9 codes. Age-adjusted incidence rates
      were calculated using the direct method with the US population in 2000 as the
      standard. RESULTS: There were 169,386 stroke hospitalizations in the database.
      Nationally, compared to whites, Asians/Pacific Islanders were more likely to have
      subarachnoid hemorrhage (incidence rate ratio {RR} female: 1.53, 95% CI 1.41
      1.65; male RR: 1.13, 95% CI 1.00-1.27) and intracerebral hemorrhage (female RR
      1.29, 95% CI 1.22-1.36; male RR: 1.58, 95% CI 1.50-1.67). However, when examined
      by geographic regions, Asians/Pacific Islanders had higher incidence rates of
      subarachnoid hemorrhage and intracerebral hemorrhage predominantly in the West,
      and lower rates of stroke elsewhere. CONCLUSION: Stroke incidence varies 3-fold
      among Asians/Pacific Islanders residing in different US regions. Geographic
      variation is less dramatic in whites. Whether genetic or cultural differences are
      responsible for dramatic heterogeneity among Asian/Pacific Islander populations
      is unclear and deserves further study.

PMID- 16280091
TI  - Prevalence of physical and verbal aggressive behaviours and associated factors
      among older adults in long-term care facilities.
AB  - BACKGROUND: Verbal and physical aggressive behaviours are among the most
      disturbing and distressing behaviours displayed by older patients in long-term
      care facilities. Aggressive behaviour (AB) is often the reason for using physical
      or chemical restraints with nursing home residents and is a major concern for
      caregivers. AB is associated with increased health care costs due to staff
      turnover and absenteeism. METHODS: The goals of this secondary analysis of a
      cross-sectional study are to determine the prevalence of verbal and physical
      aggressive behaviours and to identify associated factors among older adults in
      long-term care facilities in the Quebec City area (n = 2,332). RESULTS: The same
      percentage of older adults displayed physical aggressive behaviour (21.2%) or
      verbal aggressive behaviour (21.5%), whereas 11.2% displayed both types of
      aggressive behaviour. Factors associated with aggressive behaviour (both verbal
      and physical) were male gender, neuroleptic drug use, mild and severe cognitive
      impairment, insomnia, psychological distress, and physical restraints. Factors
      associated with physical aggressive behaviour were older age, male gender,
      neuroleptic drug use, mild or severe cognitive impairment, insomnia and
      psychological distress. Finally, factors associated with verbal aggressive
      behaviour were benzodiazepine and neuroleptic drug use, functional dependency,
      mild or severe cognitive impairment and insomnia. CONCLUSION: Cognitive
      impairment severity is the most significant predisposing factor for aggressive
      behaviour among older adults in long-term care facilities in the Quebec City
      area. Physical and chemical restraints were also significantly associated with
      AB. Based on these results, we suggest that caregivers should provide care to
      older adults with AB using approaches such as the progressively lowered stress
      threshold model and reactance theory which stress the importance of paying
      attention to the severity of cognitive impairment and avoiding the use of
      chemical or physical restraints.

PMID- 16280093
TI  - Ivermectin imposes selection pressure on P-glycoprotein from Onchocerca volvulus:
      linkage disequilibrium and genotype diversity.
AB  - Widespread use of ivermectin (IVM) as part of the Onchocerciasis Control Program
      (OCP) in West Africa could influence the evolution of the human filarial parasite
      Onchocerca volvulus. Use of IVM, in some areas for 15 years, may have restricted
      genetic diversity of O. volvulus, resembling effects attributed to a population
      bottleneck. Large population-based chemotherapy programmes, such as the OCP, may
      impose strong selection pressure on parasites and an examination of possible
      genetic selection by IVM in O. volvulus is warranted. IVM is a substrate for P
      glycoprotein; a homologue from O. volvulus (OvPGP) has been linked with IVM
      sensitivity. Linkage disequilibrium (LD) patterns of 28 genetic markers spanning
      the OvPGP locus were examined in 4 O. volvulus populations from the Volta Region
      of Ghana, West Africa. Reduced gene diversity, increased heterozygosity and an
      increase in the number of markers not in Hardy-Weinberg equilibrium were
      associated with increasing IVM treatment. The number of regions in LD decreased
      with treatment and with time. However, between 1999 and 2002, seven regions of
      OvPGP were always in complete LD, while surrounding areas showed a reduction in
      genetic variation. The use of IVM for onchocerciasis control has imposed strong
      selection on O. volvulus populations, reducing genetic variation and disrupting
      LD.

PMID- 16280094
TI  - Successive changes in tissue migration capacity of developing larvae of an
      intestinal nematode, Strongyloides venezuelensis.
AB  - Infective larvae of an intestinal nematode, Strongyloides venezuelensis, enter
      rodent hosts percutaneously, and migrate through connective tissues and lungs.
      Then they arrive at the small intestine, where they reach maturity. It is not
      known how S. venezuelensis larvae develop during tissue migration. Here we
      demonstrate that tissue invasion ability of S. venezuelensis larvae changes
      drastically during tissue migration, and that the changes are associated with
      stage-specific protein expression. Infective larvae, connective tissue larvae,
      lung larvae, and mucosal larvae were used to infect mice by various infection
      methods, including percutaneous, subcutaneous, oral, and intraduodenal
      inoculation. Among different migration stages, only infective larvae penetrated
      mouse skin. Larvae, once inside the host, quickly lost skin penetration ability,
      which was associated with the disappearance of an infective larva-specific
      metalloprotease. Migrating larvae had connective tissue migration ability until
      in the lungs, where larvae became able to settle down in the intestinal mucosa.
      Lung larvae and mucosal larvae were capable of producing and secreting adhesion
      molecules.

PMID- 16280095
TI  - Proposal to use pentoxifylline and Lyprinol therapy for chronic inflammatory
      diseases.

PMID- 16280092
TI  - Autoantibody profiles in the sera of patients with Q fever: characterization of
      antigens by immunofluorescence, immunoblot and sequence analysis.
AB  - Recent reports have shown that some of the immunological aspects of Q fever, a
      rickettsiosis caused by Coxiella burnetii, could be related to self-antigen
      responses. The aim of this study was to determine the specificity of the
      autoantibody response of patients with acute and chronic Coxiella infections.
      Smooth muscle and cardiac muscle-specific autoantibodies were observed in
      significant percentages in acutely or chronically affected Q fever patients when
      compared to healthy volunteers. Moreover, the incidence of cardiac muscle
      specific autoantibody was significantly higher among chronically ill patients
      compared to acutely ill patients. Moreover, a band of 50 kD of a HeLa extract was
      detected in most of the sera of individuals with chronic infections and previous
      sequence analysis suggests that this antigen presents a high degree of homology
      with the human actin elongation factor 1 alpha. Further research would be
      necessary to confirm if antibodies to human cytoskeletal proteins could be of
      clinical importance in chronically infected Q fever patients.

PMID- 16280096
TI  - Serum deprivation and re-addition: effects on cyclooxygenase inhibitor
      sensitivity in cultured glia.
AB  - A number of drugs were assessed for their ability to inhibit stimulus-evoked
      prostanoid synthesis in cultured glia. These drugs included non-selective
      cyclooxygenase (COX) inhibitors and those considered to be selective for the
      inducible isoform of this enzyme (COX-2). Experiments were carried out on normal
      cultures and those which had been maintained in serum-free growth medium for four
      days then re-exposed to serum for a further seven days. All of the drugs tested
      elicited concentration-dependent inhibitions of arachidonic acid (AA)-stimulated
      thromboxane B(2) (TXB(2)) accumulation in normal cultures with the following rank
      order of potency: indomethacin > piroxicam > nimesulide = NS398 > ibuprofen >>
      aspirin > paracetamol. In cultures which had been deprived of serum for four
      days, basal and AA-stimulated TXB(2) production was considerably reduced, as was
      the amount of COX immunoreactivity determined by Western blotting. Basal and AA
      stimulated TXB(2) production together with COX immunoreactivity were restored to
      control levels by the re-addition of serum to serum-deprived cultures for 7 days.
      In these cultures, the rank order of potency was: indomethacin > piroxicam >>
      ibuprofen > nimesulide = NS398 >> aspirin > paracetamol; however, there were
      marked charges in the apparent IC(50) values for particular drugs. Indomethacin,
      piroxicam and aspirin were very similar to control, but the potencies of
      ibuprofen (3-fold), NS398 (30-fold) and nimesulide (40-fold) were found to be
      decreased when compared to control. Paracetamol, on the other hand, was found to
      be almost 3-fold more potent under these conditions. Glia appear to express a COX
      with a novel sensitivity to particular inhibitors following serum deprivation and
      re-addition.

PMID- 16280097
TI  - Comparative study of anti-inflammatory and ulcerogenic activities of different
      cyclo-oxygenase inhibitors.
AB  - The aim of the present work was to study the in vivo anti-inflammatory activity
      of six NSAIDs, ibuprofen, diclofenac, nimesulide, meloxicam, celecoxib and
      rofecoxib, using the rat air-pouch model of inflammation to characterize the
      ability of these drugs to induce gastric damage and PGE(2) inhibition. Selective
      compounds were observed to have no ulcerogenic properties at anti-inflammatory
      doses; however, these drugs were weaker inhibitors of several inflammatory
      aspects such as cell influx and exudate formation. In contrast, the non-selective
      and preferential compounds present anti-inflammatory properties at lower doses
      than presented by selective drugs. At anti-inflammatory doses, only meloxicam and
      ibuprofen produced gastric damage and inhibition of PGE(2) synthesis, suggesting
      that ulcerogenic properties of NSAIDs cannot be predicted by their selectivity
      index, since meloxicam demonstrates ulcerogenic properties despite its
      preferential profile.

PMID- 16280098
TI  - Endothelin-1-dependent up-regulation of leptin production in gastric mucosal
      injury by indomethacin.
AB  - Leptin, a multifunctional hormone that regulates food intake and metabolic and
      endocrine responses, has emerged recently as an important modulatory factor in
      gastric mucosal resistance to injury. In this study, we applied the animal model
      of gastric mucosal injury caused by indomethacin to investigate the role of
      endothelin-1 (ET-1) in the mucosal leptin production. Using groups of rats
      subjected to intragastric administration of indomethacin (at 0-60 mg/kg), we show
      that gastric mucosal damage reached a maximum 4 h following the drug, and was
      accompanied by a marked elevation (up to 3.5-fold) in the mucosal leptin level,
      up to 4-fold enhancement in the expression of endothelin-converting enzyme-1 (ECE
      1) activity and up to 4.5-fold increase in ET-1 generation. Pretreatment with
      phosphoramidon, an inhibitor of ECE-1 activity, not only led to a decline in ECE
      1 and ET-1 generation, but also produced a dose-dependent reduction in the
      mucosal level of leptin and the extent of mucosal damage caused by indomethacin.
      This effect of phosphoramidon, however, was subject to suppression by the
      exogenous ET-1 administration. Moreover, a marked drop in the mucosal level of
      leptin and the reduction in the severity of mucosal damage was attained following
      pretreatment with ET(A) receptor antagonist BQ610, but not by ET(B) receptor
      antagonist BQ788. The results implicate ET-1 as a key factor in the regulation of
      leptin production associated with gastric mucosal response to injury, and show
      that the stimulatory effect of ET-1 on leptin production occurs via ET(A)
      receptor activation.

PMID- 16280100
TI  - Anti-inflammatory activity of aqueous leaf extract of Chromolaena odorata.
AB  - The anti-inflammatory activity of the aqueous extract of Chromolaena odorata was
      investigated in rats using the carrageenan-induced oedema, cotton pellet
      granuloma and formalin-induced oedema methods. The extract was administered
      orally at doses of 25, 50, 100 and 200 mg/kg. In the carrageenan method the paw
      oedema was significantly reduced by all the doses of the extract administered,
      with the 200 mg/kg dose producing the highest oedema inhibition (80.5%). In the
      cotton pellet method, granuloma weight was significantly reduced from 14 +/- 0.1
      to 9.0 +/- 0.1 mg, while in the formaldehyde induced arthritis the extract
      inhibited the oedema during the 10-day period. In conclusion, this study has
      established the anti-inflammatory activity of C. odorata and, thus, justifies the
      traditional uses of the plant in the treatment of wounds and inflammation.

PMID- 16280099
TI  - Peripheral and central activation of nitric oxide-cyclic GMP pathway by
      sildenafil.
AB  - Experimental studies have indicated the importance of cAMP and cGMP in modulation
      of peripheral sensory neurons leading to hyperalgesic response. The concentration
      of both depends upon the activity of phosphodiesterase, which is responsible for
      their degradation. The aim of the present study was to evaluate the effect of the
      PDE-5 inhibitor sildenafil on central or peripheral administration in formalin
      induced hyperalgesia in rats. Sildenafil dose-dependently and significantly
      attenuated both the early and late phase of formalin-induced hyperalgesia on
      central administration. However, sildenafil on peripheral administration
      inhibited only the late phase of formalin-induced hyperalgesia in rats. The anti
      nociceptive effect of sildenafil was blocked by L-NAME, a non-selective NOS
      inhibitor, and methylene blue (MB), a guanylate cyclase inhibitor, but sildenafil
      itself had little or no effect on the first phase of the formalin test in rats.
      The results from the present study indicates that sildenafil, besides peripheral
      actions, has a central anti-nociceptive effect, which may be due to activation of
      the NO-cGMP pathway, as this effect was blocked by L-NAME and MB. PDE-5
      inhibitors could be considered as a new class of anti-nociceptive agents for
      future drug development.

PMID- 16280101
TI  - Anti-inflammatory properties of kefir and its polysaccharide extract.
AB  - Kefir is a fermented beverage originating form the Caucasian regions composed of
      a number of bacteria and yeasts living together in polysaccharide grains secreted
      by them. Kefir can be considered a probiotic source as it presents anti
      bacterial, anti-mycotic, anti-neoplasic and immunomodulatory properties. Aiming
      to appraise a possible anti-inflammatory effect of kefir we conducted cotton
      induced granuloma and paw oedema assays in rats, the latter using carrageenan,
      dextran and histamine as stimuli. Kefir samples were thawed and continuously
      cultured during 15 days both in a molasses solution (50 g/l) and in cow's milk. A
      polysaccharide extract isolated from the grains (kefiran) was also tested in
      cotton-pellet experiments. The results showed significant inhibition in the
      formation of granuloma tissue for all the test groups, as compared to the blank
      group. Kefir suspensions in molasses presented an inhibition of 41 +/- 3% for the
      inflammatory process, fermented milk prepared from kefir showed 44 +/- 6%
      inhibition and kefiran extract 34 +/- 15%. Rat paw oedema also showed significant
      decreases with the mediators. Dextran-induced oedema was completely inhibited at
      1 h after input, with a 76% inhibition after 2 h. Carrageenan stimulus was
      inhibited 62% after the 3rd hour, and histamine by 52% after the 2nd hour. These
      results points to the existence of anti-inflammatory prebiotic compounds present
      in symbiotic cultures of kefir growing in both aqueous and milky suspensions.

PMID- 16280102
TI  - Anti-inflammatory activity of Justicia prostrata gamble in acute and sub-acute
      models of inflammation.
AB  - In this study, the aqueous (AQJP) and alcoholic (ALJP) extracts of the whole
      plant of Justicia prostrata Gamble (Acanthaceae) were screened for their acute
      and subacute anti-inflammatory activities using carrageenan-induced acute
      inflammation and cotton-pellet-induced granuloma (subacute inflammation),
      respectively, in rats. In the carrageenan-induced rat paw oedema model, both
      extracts were found to exhibit maximum reduction in paw volume at the first hour
      in a dose-dependent manner. At the dose of 500 mg/kg p.o., both extracts AQJP and
      ALJP showed maximum inhibition (51.39% and 62.5%, respectively) in rat paw oedema
      volume at the first hour of carrageenan-induced acute inflammation. In the cotton
      pellet granuloma assay, AQJP and ALJP at the dose of 500 mg/kg p.o. suppressed
      the transudative, exudative and proliferative phases of chronic inflammation.
      These extracts were able to (i) reduce the lipid peroxide content of exudates and
      liver and (ii) normalize the increased activity of acid and alkaline phosphatases
      in serum and liver of cotton pellet granulomatous rats. Preliminary phytochemical
      screening revealed the presence of lignans, triterpenes and phenolic compounds in
      ALJP, whereas phenolic compounds and glycosides in AQJP. The anti-inflammatory
      properties of these extracts may possibly be due to the presence of phenolic
      compounds. The anti-inflammatory effects produced by the extracts at the dose of
      500 mg/kg, p.o. was comparable with the reference drug diclofenac sodium (5 mg/kg
      p.o.).

PMID- 16280104
TI  - New advances in the management of metastatic breast cancer.

PMID- 16280105
TI  - Update: NCCN small cell and non-small cell lung cancer Clinical Practice
      Guidelines.

PMID- 16280106
TI  - Advances in the development of a therapeutic cancer vaccine.

PMID- 16280107
TI  - New approaches in the management of lung cancer.

PMID- 16280108
TI  - Update: NCCN colon cancer Clinical Practice Guidelines.

PMID- 16280110
TI  - Proteasome inhibitors in non-Hodgkin's lymphoma.

PMID- 16280111
TI  - Farnesyl transferase inhibition in hematologic malignancies.

PMID- 16280109
TI  - Update: NCCN prostate cancer Clinical Practice Guidelines.

PMID- 16280112
TI  - Trends in the management of chronic myelogenous leukemia.

PMID- 16280113
TI  - Comparative studies on erythropoietic agents.

PMID- 16280114
TI  - Management of deep vein thrombosis in cancer patients.

PMID- 16280115
TI  - New trends in the management of oral mucositis.

PMID- 16280116
TI  - Understanding the relationship between chronic and acute pain.

PMID- 16280117
TI  - Management of bone metastases: 2005 update.

PMID- 16280118
TI  - Update: NCCN breast cancer Clinical Practice Guidelines.

PMID- 16280119
TI  - Empirical Bayesian analysis of accident severity for motorcyclists in large
      French urban areas.
AB  - The present article deals with individual probabilities of different levels of
      injury in case of a motorcycle accident. The approach uses an empirical Bayesian
      method based on the Multinomial-Dirichlet model, see [Leonard, T., 1977. A
      Bayesian approach to some Multinomial estimation and pretesting problems, J. Am.
      Stat. Association, 72, 869-874], to conduct an analysis of the probability
      distributions about the severity of accidents at the level of individuals in
      large and dense French urban areas during year 2003. We model accident severity
      using four levels of injury: material damages only, slight injury, severe injury,
      fatal injury. Our application shows that sociodemographic characteristics of
      motorcyclists and factors influencing their speed behaviors, the suddenness of
      their collision and the vigilance of road users play significant roles on the
      shapes of their probability distributions of accident severity. The computation
      of posterior distributions of the levels of injury for different groups of
      motorcyclists enables us to rank them with respect to their risk of injury using
      second order stochastic dominance orderings. It is found that women motorcyclists
      between 30 and 50 years old driving powerful motorcycles are the most exposed to
      risk of injury.

PMID- 16280121
TI  - Unmet medical needs in antibacterial therapy.
AB  - The innate and evolutionary resourcefulness of bacterial pathogens virtually
      guarantees that there will always be important areas in which antimicrobial
      therapy can be improved. Current areas of need, or ones that are anticipated to
      be problematic in the near future include nosocomial infections caused by multi
      resistant Gram-negative bacteria, where the variety and prevalence of multidrug
      efflux pumps provides a particular challenge to the designers of new drugs. In
      the community setting, the current prevalence of ampicillin and trimethoprim
      sulfamethoxazole resistance, and the growing prevalence of fluoroquinolone
      resistance in Escherichia coli portend a need for new classes of oral agents to
      address this important need. On the Gram-positive side, the rapid increase in
      virulent community-acquired methicillin-resistant Staphylococcus aureus (MRSA)
      infections as a cause of pneumonia emphasizes the importance of developing more
      agents that are active against MRSA and that are effective for treating
      pneumonia. Finally, the importance of indwelling devices as a nidus for
      nosocomial infections emphasizes the need for effective agents for treating
      biofilm-associated device infection both inside and outside of the hospital.

PMID- 16280120
TI  - Analysis of T-cell responses in malaria-exposed and non-exposed donors using
      Plasmodium falciparum asexual blood stages enriched by a simple centrifugation
      method.
AB  - Several studies have reported on similar in vitro cellular responses to different
      malaria-antigen preparations in both malaria-primed and un-primed donors. Whether
      intact live parasites can exert a distinct type of response in either of the two
      groups is not well known. In this study, we developed a simple three-step
      centrifugation method for simultaneous enrichment of early and late blood stages
      from Plasmodium falciparum cultures. Such enriched P. falciparum fractions and
      other antigen preparations were used to stimulate lymphocytes from malaria
      exposed and non-exposed individuals to examine the proliferative activity and
      expansion of CD3+, gammadelta+, CD4+, and CD8+ T cells. While lymphocytes from
      malaria non-exposed donors proliferated relatively higher than those from malaria
      exposed donors in response to most antigens tested, the enriched fractions of
      live parasites exerted higher proliferative responses on cells from the latter
      donors. This suggests the existence of memory cells in the malaria-exposed
      donors, but not in the non-exposed ones. Flow cytometric analysis revealed a
      higher percentage expansion of CD4+ T cells in the responding cells of the
      exposed donors than the non-exposed ones. Taken together, this study reports on a
      simple method that simultaneously enriches for intact live early and late blood
      stages of P. falciparum parasites. Moreover, the study revealed higher expansion
      CD4+ T cells in the exposed individuals than the non-exposed in response to live
      malaria parasites and not to other parasite-antigen preparations.

PMID- 16280123
TI  - Elevated serum levels of proinflammatory cytokines and biomarkers of matrix
      remodeling in never-treated patients with familial hypercholesterolemia.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is a common inherited disorder of
      lipoprotein metabolism, whose origin involves mutations in the gene coding for
      the low-density lipoprotein receptor protein. Although FH is monogenic, wide
      variation occurs in the onset and severity of atherosclerosis in these patients.
      METHODS: Since data on levels of inflammatory proteins and/or active factors in
      FH patients who have never received lipid-lowering treatment are lacking, serum
      levels of MMP-3, active MMP-9 and TIMP-1 as well as pro-inflammatory cytokines
      (TNF-alpha, IL-18) were determined in never-treated homozygous FH Moroccan
      patients (n=4) and compared to those of heterozygous FH subjects (n=7) and of
      healthy control subjects (n=5). RESULTS: When compared to controls, homozygous FH
      patients exhibited levels of active MMP-9 and TIMP-1 (p<0.05), and of both high
      sensitive-CRP and IL-18 which were significantly elevated (p<0.05 and p<0.01,
      respectively). In heterozygous FH patients, intermediate values between FH
      homozygotes and healthy controls were observed for these markers, with the
      exception of MMP-9 activity whose levels were significantly elevated (p<0.05).
      Multivariate analysis revealed a positive correlation between apolipoprotein B,
      TIMP-1 and IL-18 levels, and between hs-CRP and IL-18 (p<0.01). CONCLUSIONS:
      Although the sample size of this FH group was limited, our data suggest that
      nontreated homozygous FH patients, and to a lesser degree heterozygous FH
      patients, exhibit not only a markedly proinflammatory vascular state but also
      pronounced extracellular matrix remodeling, as reflected by elevated circulating
      levels of inflammatory cytokines and MMPs.

PMID- 16280122
TI  - CysLT1 leukotriene receptor antagonists inhibit the effects of nucleotides acting
      at P2Y receptors.
AB  - Montelukast and pranlukast are orally active leukotriene receptor antagonists
      selective for the CysLT1 receptor. Conversely, the hP2Y(1,2,4,6,11,12,13,14)
      receptors represent a large family of GPCRs responding to either adenine or
      uracil nucleotides, or to sugar-nucleotides. Montelukast and pranlukast were
      found to inhibit nucleotide-induced calcium mobilization in a human monocyte
      macrophage like cell line, DMSO-differentiated U937 (dU937). Montelukast and
      pranlukast inhibited the effects of UTP with IC50 values of 7.7 and 4.3 microM,
      respectively, and inhibited the effects of UDP with IC50 values of 4.5 and 1.6
      microM, respectively, in an insurmountable manner. Furthermore, ligand binding
      studies using [3H]LTD4 excluded the possibility of orthosteric nucleotide binding
      to the CysLT1 receptor. dU937 cells were shown to express P2Y2, P2Y4, P2Y6,
      P2Y11, P2Y13 and P2Y14 receptors. Therefore, these antagonists were studied
      functionally in a heterologous expression system for the human P2Y receptors. In
      1321N1 astrocytoma cells stably expressing human P2Y(1,2,4,6) receptors, CysLT1
      antagonists inhibited both the P2Y agonist-induced activation of phospholipase C
      and intracellular Ca2+ mobilization. IC50 values at P2Y1 and P2Y6 receptors were
      <1 microM. In control astrocytoma cells expressing an endogenous M3 muscarinic
      receptor, 10 microM montelukast had no effect on the carbachol-induced rise in
      intracellular Ca2+. These data demonstrated that CysLT1 receptor antagonists
      interact functionally with signaling pathways of P2Y receptors, and this should
      foster the study of possible implications for the clinical use of these compounds
      in asthma or in other inflammatory conditions.

PMID- 16280124
TI  - Bifocal and PP1 interaction regulates targeting of the R-cell growth cone in
      Drosophila.
AB  - Bifocal is a putative cytoskeletal regulator and a Protein phosphatase-1 (PP1)
      interacting protein that mediates normal photoreceptor morphology in Drosophila.
      We show here that Bif and PP1-87B as well as their ability to interact with each
      other are required for photoreceptor growth cone targeting in the larval visual
      system. Single mutants for bif or PP1-87B show defects in axonal projections in
      which the axons of the outer photoreceptors bypass the lamina, where they
      normally terminate. The data show that the functions of bif and PP1-87B in either
      stabilizing R-cell morphology (for Bif) or regulating the cell cycle (for PP1
      87B) can be uncoupled from their function in visual axon targeting.
      Interestingly, the axon targeting phenotypes are observed in both PP1-87B mutants
      and PP1-87B overexpression studies, suggesting that an optimal PP1 activity may
      be required for normal axon targeting. bif mutants also display strong genetic
      interactions with receptor tyrosine phosphatases, dptp10d and dptp69d, and
      biochemical studies demonstrate that Bif interacts directly with F-actin in
      vitro. We propose that, as a downstream component of axon signaling pathways, Bif
      regulates PP1 activity, and both proteins influence cytoskeleton dynamics in the
      growth cone of R cells to allow proper axon targeting.

PMID- 16280125
TI  - Mechanisms differentiating normal from abnormal aggression: glucocorticoids and
      serotonin.
AB  - Psychopathology-associated human aggression types are induced by a variety of
      conditions, are behaviorally variable, and show a differential pharmacological
      responsiveness. Thus, there are several types of abnormal human aggression. This
      diversity was not reflected by conventional laboratory approaches that focused on
      the quantitative aspects of aggressive behavior. Recently, several laboratory
      models of abnormal aggression were proposed, which mainly model hyperarousal
      driven aggressiveness (characteristic to intermittent explosive disorder, post
      traumatic stress disorder, depression, chronic burnout, etc.) and hypoarousal
      driven aggressiveness (characteristic mainly to antisocial personality disorder
      and its childhood antecedent conduct disorder). Findings obtained with these
      models suggest that hyperarousal-driven aggressiveness has at its roots an
      excessive acute glucocorticoid stress response (and probably an exaggerated
      response of other stress-related systems), whereas chronic hypoarousal-associated
      aggressiveness is due to glucocorticoid deficits that affect brain function on
      the long term. In hypoarousal-driven aggressiveness, serotonergic
      neurotransmission appears to lose its impact on aggression (which it has in
      normal aggression), certain prefrontal neurons are weakly activated, whereas the
      central amygdala (no, or weakly involved in the control of normal aggression)
      acquires important roles. We suggest that the specific study of abnormal aspects
      of aggressive behavior would lead to important developments in understanding the
      specific mechanisms underlying different forms of aggression, and may ultimately
      lead to the development of better treatment approaches.

PMID- 16280126
TI  - A genome-wide linkage scan for ankle-brachial index in African American and non
      Hispanic white subjects participating in the GENOA study.
AB  - Little is known about the genetics of peripheral arterial disease (PAD). We
      performed linkage analyses to identify genomic regions that influence ankle
      brachial index (ABI), a measure of PAD, in 1310 African Americans (AA) (mean age
      62+/-9 years) and 796 non-Hispanic whites (NHW) (mean age 58+/-9 years) belonging
      to hypertensive sibships. ABI was determined at two sites in each lower extremity
      and the lower of the two average ABIs was used in the analyses after adjustment
      for age, age(2), sex, weight, total cholesterol, HDL cholesterol, and ever
      smoking. Genotypes were measured at microsatellite marker loci spaced
      approximately 10cM apart across the 22 autosomes. Heritability was assessed by
      SOLAR and linkage analyses performed using a variance components approach. Modest
      heritability (h(2)) was noted for the fully adjusted ABI in each ethnic group
      (h(2)=0.195, P=0.002 in AA; h(2)=0.212, P=0.006 in NHW). Univariate linkage
      analyses demonstrated tentative evidence of linkage (multipoint LOD=1.3-2.0) for
      ABI on chromosomes 1p, 6q, 7q, 10p, and 16p in AA and on chromosome 3p and 3q in
      NHW. In conclusion, ABI is a modestly heritable trait in AA and NHW hypertensive
      sibships. Quantitative trait linkage analyses identified several chromosomal
      regions that may harbor genes influencing ABI.

PMID- 16280127
TI  - Site-specific influence of polyunsaturated fatty acids on atherosclerosis in
      immune incompetent LDL receptor deficient mice.
AB  - Polyunsaturated fatty acids (PUFA) are thought to influence plasma lipid levels,
      atherosclerosis, and the immune system. In this study, we fed male LDL receptor
      deficient (LDLR(-/-)) mice and immune incompetent LDLR(-/-) RAG2(-/-) mice diets
      containing predominantly saturated fats (milk fat) or PUFA (safflower oil) to
      determine if the response to diet was influenced by immune status. Relative to
      milk fat diet, plasma lipid and VLDL levels in both the LDLR(-/-) and LDLR(-/-)
      RAG2(-/-) mice fed safflower oil diet were lower, suggesting that the primary
      effect of PUFA on plasma lipids was not due to its inhibition of the immune
      system. Neither diet nor immune status influenced hepatic triglyceride production
      and post-heparin lipase activity, suggesting that the differences in triglyceride
      levels are due to differences in rates of catabolism of triglyceride-rich
      lipoproteins. While both diets promoted atherogenesis, both aortic root and
      innominate artery atherosclerosis in LDLR(-/-) mice was less in safflower oil fed
      animals. In contrast, a site-specific effect of PUFA was observed in the immune
      incompetent LDLR(-/-) RAG2(-/-). In these mice, aortic root atherosclerosis, but
      not innominate artery atherosclerosis, was less in PUFA fed animal. These results
      suggest that PUFA and the immune system may influence innominate artery
      atherosclerosis by some overlapping mechanisms.

PMID- 16280128
TI  - Determination of volatile oak compounds in wine by headspace solid-phase
      microextraction and gas chromatography-mass spectrometry.
AB  - A headspace solid-phase microextraction (HS-SPME) and gas chromatography (GC)
      coupled to mass spectrometry (MS) method was developed to identify and quantify
      14 volatile oak compounds in aged red wines. The most important HS-SPME variables
      were optimised by experimental design technique in order to improved the
      extraction process. The selected conditions were: 10 mL of sample in 20 mL sealed
      vials with addition of 30% of sodium chloride (saturated solution),
      divinylbenzene-carboxen-polydimethylsiloxane (DVB-CAR-PDMS) fibre, 10 min of pre
      incubation time, 70 degrees C of temperature and 60 min of extraction time
      without agitation. The features of the method were established for the studied
      compounds in terms of linear range, slope and intercept of the calibration
      graphs, detection and quantification limits and repeatability. For all compounds
      detection limits were below their threshold levels and repeatability, in terms of
      relative standard deviation, was good, with values between 3 and 11%. Finally,
      the method was applied to the analysis of six aged red wines by both internal
      standard and standard addition calibration methods. The concentrations obtained
      with both methods were statistically compared.

PMID- 16280129
TI  - Enumeration and detection of aerosolized Aspergillus fumigatus and Penicillium
      chrysogenum conidia and hyphae using a novel double immunostaining technique.
AB  - The identification of collected airborne unicellular fungal conidia and hyphae
      using nonviable techniques is subjective and an imprecise process. Similarly, to
      determine whether an individual is allergic to a particular genus requires a
      separate immunodiagnostic analysis. This study demonstrates the development of a
      novel double immunostaining halogen assay, which enables (1) the simultaneous
      identification of collected airborne fungal conidia and hyphae of Aspergillus
      fumigatus and Penicillium chrysogenum using monoclonal antibodies and (2) the
      demonstration of patient-specific allergy to the same particles using human serum
      IgE. The results demonstrate that when conidia were ungerminated the binding of
      antibodies was homogeneous and localized in close proximity around the entire
      conidia for both species. However, when conidia were germinated, the proportion
      expressing antigen increased (P < 0.0001) for both species and the sites of
      binding of the two antibodies changed with double immunostaining restricted to
      the hyphal tips for A. fumigatus, in addition to the sites of germination for P.
      chrysogenum. The described immunoassay has the potential to identify fungal
      particles in personal environmental air samples, provided species-specific
      monoclonal antibodies are available, while simultaneously demonstrating allergic
      sensitization to the same particles by co-staining the samples with the patient's
      own serum. Such an immunoassay can use those fungi that the patient is actually
      exposed to and potentially avoids many problems associated with extract
      variability based on the performance of current diagnostic techniques for fungal
      allergy.

PMID- 16280131
TI  - Altruism, sex, and inbreeding when the genotype-phenotype map is additive.
AB  - Recently published theoretical results suggest that, in a sexual population, when
      genotypes code for phenotypes in a complex manner, it is possible for altruistic
      genotypes to spread through a metapopulation (i.e. through a collection of
      subpopulations). This spread tends to occur during periods when the environment
      deteriorates throughout the metapopulation. By contrast, under asexual
      reproduction, non-altruistic genotypes seem to be favoured, at least when
      subpopulations are substantial in size. The most relevant previous study makes
      use of Kauffman and Levin's "NK model" as a way to relate genotypes to fitness.
      Unfortunately, there are both conceptual and technical problems with the
      application of the NK model to populations that contain many different genotypes
      (e.g. polymorphic diploid populations with more than a few loci under selection).
      The present study presents a more tractable and biologically plausible model to
      study the causal relationship between sexual reproduction and altruism. In
      particular, phenotypes are determined by additive interactions among alleles at
      different loci in a diploid genome, with up to 200 loci under selection. In
      addition, subpopulations are substantially larger than those considered in the
      most relevant previous work. The results show that, so long as there are multiple
      "fitness peaks" in "phenotype space", the additive genotype-phenotype map leads
      to results that are similar to those from the NK model. Various parameters are
      manipulated in an effort to discover the determinants of altruistic and non
      altruistic outcomes. The findings should facilitate further investigations, and
      they should help to establish the plausibility of the suggested relationship
      between sexual reproduction and altruism. The results also suggest that
      inbreeding can lead to a similar result as asexuality. That is, inbreeding seems
      to enhance the probability that altruistic phenotypes will be eliminated.

PMID- 16280130
TI  - Tryptophan supports interaction of transmembrane helices.
AB  - Interactions of transmembrane helices play an important role in folding and
      oligomerization of integral membrane proteins. The interfacial residues of these
      helices frequently correspond to heptad repeat motifs. In order to uncover novel
      mechanisms underlying these interactions, we randomised a heptad repeat pattern
      with a complete set of amino acids. Those sequences that were capable of high
      affinity self-interaction upon integration into bacterial inner membranes were
      selected by means of the POSSYCCAT system. A comparison between selected and non
      selected sequences reveals that high-affinity sequences were strongly enriched in
      tryptophan residues that accumulated at specific positions of the heptad motif.
      Mutation of Trp in selected clones significantly reduced self-interaction of the
      transmembrane segments without affecting their efficiency of membrane
      integration. Conversely, grafting Trp onto artificial transmembrane segments
      strongly enhanced their interaction. We conclude that tryptophan supports
      interaction of transmembrane segments.

PMID- 16280132
TI  - IL4 receptor polymorphism is associated with increased risk of sudden deafness in
      Korean population.
AB  - The interleukin 4 receptor (IL4R) polymorphism Q576R (rs 180275) has been well
      known to be associated with atopy and other inflammatory diseases. A single
      nucleotide polymorphism (SNP) A > G transition potentiates the binding
      specificity of the adjacent tyrosine residue. In this study we investigated the
      possible relationship between sudden deafness (SD) and IL4R polymorphism Q576R in
      97 Korean SD patients and 613 controls using pyrosequencing method. The odds
      ratio (OR) for SD associated with the G vs. A allele was 2.58 [P < 0.0001, 95%
      confidence interval (CI) = 1.84-3.60]. We then sub-grouped SD into Tinnitus
      positive (+) and Tinnitus negative (-). G allele in Tinnitus (+) is significantly
      associated with the development of Tinnitus (+) [X(2) = 32.02, P < 0.0001, OR
      (95% CI) = 2.74 (1.91-3.93)] but not with Tinnitus (-). Taken together these
      results suggest that G allele could be a risk factor for SD.

PMID- 16280133
TI  - Non-neuronal nicotinic alpha 7 receptor, a new endothelial target for
      revascularization.
AB  - Alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) is widely expressed in
      the central and peripheral nervous systems, and is also found in several non
      neuronal tissues, such as endothelial cells (ECs), bronchial epithelial cells,
      skin keratinocytes and vascular smooth muscle cells. Recent evidence suggests
      that alpha7 nAChR is involved in angiogenesis. Here, we investigated the
      feasibility of alpha7 nAChR for revascularization in ischemic heart disease. RT
      PCR and immunohistochemistry were used to examine the expression of alpha7 nAChR
      in human umbilical vein endothelial cell (HUVECs). The cellular function was
      examined using MTT, fluorescence confocal microscopy and angiogenesis assay in
      vitro. The capillary density in the rat model of myocardial infarction (MI) was
      investigated using immunohistochemistry. The results showed that alpha7 nAChR
      agonists choline increased the expression of alpha7 nAChR mRNA and protein, the
      intracellular Ca 2+ concentration, proliferation and tube formation of ECs.
      Reverse effects were observed by using alpha7 nAChR antagonist alpha-BTX.
      Furthermore, in the rat model of MI, alpha7 nAChR agonist enhanced the capillary
      density in ischemic tissues, whereas antagonist mecamylamine and alpha-BTX
      inhibited the effect. Our results suggest that alpha7 nAChR is involved in the
      regulation of cellular function in ECs, and capillary formation in MI, which are
      the important steps of angiogenesis. Therefore, alpha7 nAChR on ECs may be a new
      endothelium target for revascularization in therapeutic angiogenesis of ischemic
      heart disease.

PMID- 16280134
TI  - Effect of Shiga-like toxin II from Escherichia coli O157:H7 on intestinal
      clearance of norfloxacin in rats.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 infection causes severe
      clinical symptoms, due to its bacterial toxin, called Shiga-like toxin (SLT).
      However, little is known about the information to establish a safe and efficient
      prescription to treat for EHEC O157:H7 patients. Thus, we investigated the effect
      of SLT-II on intestinal function in rats by using the antibiotic norfloxacin
      (NFLX) as a model drug. The intestinal clearance (CLi) of NFLX, determined by
      loop method in the jejunum, was significantly decreased by SLT-II. In
      histopathological experiment, epithalaxia was observed in SLT-II-treated rats
      without structural changes of tight junction suggesting the deterioration of
      active transport systems by SLT-II. CLi of NFLX in normal rats was decreased by
      carnitine (CAR), suggesting the possible involvement of CAR-sensitive transporter
      in CLi of NFLX. Taken together, these results suggest that the EHEC O157:H7
      infection might affect the intestinal disposition of NFLX due to the changing
      intestinal expression/function of drug transporters by SLT-II.

PMID- 16280136
TI  - Evodiamine inhibits in vitro angiogenesis: Implication for antitumorgenicity.
AB  - Evodiamine, the major bioactive compound isolated from Chinese herbal drug named
      Wu-Chu-Yu, has been reported to exhibit anti-tumor growth and metastasis.
      However, the effect of evodiamine on angiogenesis remains to be investigated. We
      used the fresh medium containing evodiamine or human lung adenocarcinoma cell
      (CL1 cells) derived conditioned media free of evodiamine to test their capability
      to induce in vitro angiogenesis, i.e., human umbilical vein endothelial cells
      (HUVECs) tube formation and invasion. We demonstrated that evodiamine could
      directly inhibit in vitro HUVECs tube formation and invasion. Locally
      administered evodiamine also inhibited the in vivo angiogenesis in the chick
      embryo chorioallantoic membrane (CAM) assay. The gene expression of vascular
      endothelial growth factor (VEGF) and the p44/p42 mitogen-activated protein kinase
      (MAPK, ERK) that correlated with endothelial cells angiogenesis were inhibited by
      evodiamine. We found that the evodiamine-treated CL1 cells derived conditioned
      medium showed decreased VEGF release and reduced ability of inducing in vitro
      tube formation. After the collection of conditioned media, the VEGF expression of
      remaining CL1 cells were determined by Western analyses and revealed that
      evodiamine decreased VEGF expression. Moreover, administration of recombinant
      human VEGF(165) (rhVEGF(165)) induced tube formation and ERK phosphorylation by
      HUVECs, and partially attenuated inhibitory effect of evodiamine. From these
      results, we suggested that evodiamine is a potent inhibitor of angiogenesis. The
      mechanism might involve at least the inhibition of VEGF expression, probably
      through repression of ERK phosphorylation.

PMID- 16280135
TI  - LPS-induced ROS generation and changes in glutathione level and their relation to
      the maturation of human monocyte-derived dendritic cells.
AB  - Lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) generation and the
      concomitant decline in the ratio of reduced glutathione (GSH) to oxidized
      glutathione (GSSG) were demonstrated in human monocyte-derived dendritic cells
      (DC). Further, their relation to the maturation of DC, characterized by the
      production of cytokines, up-regulation of cell surface molecules and allo
      stimulatory capacity, was examined. The LPS-induced ROS generation was
      demonstrated using electron paramagnetic resonance spectroscopy in intact cells,
      and was also confirmed using laser scanning confocal microscopy. The GSH/GSSG was
      assesed using a glutathione assay kit. When the DC were treated with alpha-phenyl
      tert-butylnitrone, the ROS generation was attenuated, but the declined GSH/GSSG
      was not attenuated, and only cytokine production was suppressed among the above
      mentioned maturation characteristics. When the DC were treated with glutathione
      monoethyl ester, both the ROS generation and the declined GSH/GSSG were
      attenuated, and the maturation characteristics were all suppressed. These
      findings suggest that the LPS-induced ROS generation and the concomitant decline
      in GSH/GSSG occur in human monocyte-derived DC and that the former is involved in
      cytokine production, while the latter is involved in the up-regulation of cell
      surface molecules and allo-stimulatory capacity. Since the cytokine production
      and the allo-stimulatory capacity of DC play an important role in inflammatory
      and immune responses, differential regulation of the ROS generation and the
      declined GSH/GSSG may be useful as therapeutic tools in diseases where both
      responses become entangled, such as sepsis and graft-versus-host disease.

PMID- 16280137
TI  - Effect of acute and chronic MK-801 administration on extracellular glutamate and
      ascorbic acid release in the prefrontal cortex of freely moving mice on line with
      open-field behavior.
AB  - The present study was designed to investigate the effects of acute and chronic
      administration of MK-801 (0.6 mg/kg), a noncompetitive NMDA-receptor antagonist
      on extracellular glutamate (Glu) and ascorbic acid (AA) release in the prefrontal
      cortex (PFC) of freely moving mice using in vivo microdialysis with open-field
      behavior. In line with earlier studies, acute administration of MK-801 induced an
      increase of Glu in the PFC. We also observed single MK-801 treatment increased AA
      release in the PFC. In addition, our results indicated that the basal AA levels
      in the PFC after MK-801 administration for 7 consecutive days were significantly
      decreased, and basal Glu levels also had a decreased tendency. After chronic
      administration (0.6 mg/kg, 7 days), MK-801 (0.6 mg/kg) challenge significantly
      decreased dialysate levels of AA and Glu. Our study also found that both acute
      and chronic administration of MK-801 induced hyperactivity in mice, but the
      intensity of acute administration was more than that of chronic administration.
      Furthermore, in all acute treatment mice, individual changes in Glu dialysate
      concentrations and the numbers of locomotion were positively correlated. In
      conclusion, this study may provide new evidence that a single MK-801
      administration induces increases of dialysate AA and Glu concentrations in the
      PFC of freely moving mice, which are opposite to those induced by repeated MK-801
      administration, with an unknown mechanism. Our results suggested that redox
      response might play an important role in the model of schizophrenic symptoms
      induced by MK-801.

PMID- 16280139
TI  - Analysis of the candidate tumor suppressor Ris-1 in primary human breast
      carcinomas.
AB  - Frequent chromosome 3 losses have been described in several tumors types, which
      strongly suggest the presence of one or several tumor suppressor genes. Recently,
      a novel candidate tumor suppressor gene termed Ris-1 (for Ras-induced senescence
      1) has been identified at chromosomal position 3p21.3. Ris-1 has been proposed to
      participate in anti-tumor responses that resemble cellular senescence and that
      are elicited by oncogenes such as Ras. To analyze the role of Ris-1 as a putative
      tumor suppressor gene in human breast cancer, we have performed a real-time
      quantitative analysis of its mRNA expression in 60 patients. Moreover, we carried
      out a first approach to evaluate the most common inactivation mechanism that can
      affect expression levels of tumor suppressor genes (mutation, promoter
      hypermethylation and allelic losses). Furthermore, a correlation study between
      expression as well as inactivating mechanisms of Ris-1 and several clinico
      pathological parameters of the tumors was designed, with the objective of
      appraising the prognostic value of Ris-1 status. Decreased expression of Ris-1
      was observed in 23% of the cases and overexpressed Ris-1 was detected in 15% of
      the primary breast tumors. Our data showed high frequency of LOH (30%) at one of
      the markers used. Nevertheless, a polymorphism related with the expression levels
      was described. Statistically significant correlations were found between
      decreased Ris-1 expression and negative progesterone receptors, as well as
      between overexpressing Ris-1 tumors and high histological grade. Despite all
      these data, we conclude that the suggested role of Ris-1 as tumor suppressor gene
      is not evident, at least in breast cancer. Future and larger series studies in
      different tumor types are necessary to clarify Ris-1 function in human cancer.

PMID- 16280138
TI  - The herbal medicine inchin-ko-to (TJ-135) induces apoptosis in cultured rat
      hepatic stellate cells.
AB  - Use of herbal remedies in the treatment of various diseases has a long tradition
      in Eastern medicine and the liver diseases are not an exception. In their use,
      lack of elucidation of mechanism(s) as well as randomized, placebo-controlled
      clinical trials has been a problem. Recently, we and others reported that inchin
      ko-to (TJ-135), one of herbal remedies, suppressed hepatic fibrosis in animal
      models. In the course of clarifying the mechanism, we directed our focus on
      hepatic stellate cells (HSCs), playing a pivotal role in hepatic fibrosis, and
      found that rat HSCs cultured with TJ-135 changed their morphology to star-like
      configuration with thin, slender and dendritic processes with fewer stress
      fibers, which might be the features in apoptosis. In fact, TJ-135 induced HSC
      apoptosis in a time- and concentration-dependent manner as judged by the nuclear
      morphology, quantitation of cytoplasmic histone-associated DNA oligonucleosome
      fragments and caspase 3 activity. In HSCs treated with TJ-135, increased
      expression of p53 and decreased expression of Bcl-2 and phosphorylated Akt and
      Bad were determined. HSC apoptosis is shown to be involved in the mechanisms of
      spontaneous resolution of rat hepatic fibrosis and the agent which induces HSC
      apoptosis has been shown to reduce experimental hepatic fibrosis in rats. Thus,
      the induction of HSC apoptosis could be the mechanism how TJ-135 works on the
      resolution of hepatic fibrosis. Our current data may shed light on the novel
      effect of the herbal remedy.

PMID- 16280140
TI  - Impact of alertness training on spatial neglect: a behavioural and fMRI study.
AB  - The effects of a 3-week computerised alertness training on chronic (>3 months)
      visuospatial hemineglect were investigated prospectively in seven patients by
      means of neuropsychological tests and functional magnetic resonance imaging
      (fMRI). Following the alertness training, the group showed improved alertness and
      a significant improvement in the performance of a neglect test battery over and
      above any improvement during a 3-week baseline phase. Improvements in the neglect
      tasks were accompanied by an increase of right hemisphere neural activity in
      frontal cortex, anterior cingulate cortex, precuneus, cuneus and angular gyrus.
      These areas have previously been associated with alertness and spatial attention.
      A similar pattern of increased neural activity was found for the left hemisphere.
      Four weeks after the end of the training, the patients' neglect test performance
      had mostly returned to baseline, while the increases in neural activity
      bilaterally in frontal areas, in the right anterior cingulate cortex, the right
      angular gyrus and the left temporoparietal cortex remained. The data show that a
      3-week computerised alertness training can improve performance both in alertness
      and neglect tests and that these behavioural improvements are associated with
      reactivation in areas associated with alerting and visuospatial attention. The
      limited stability of these effects over time suggests that a 3-week alertness
      training alone does not result in long lasting improvements in every patient, but
      refining the treatment protocol may lead to a more stable amelioration of neglect
      symptoms.

PMID- 16280141
TI  - Perinatal programming and functional teratogenesis: impact on body weight
      regulation and obesity.
AB  - It is increasingly accepted that alterations of the intrauterine and early
      postnatal nutritional, metabolic, and hormonal environment may cause
      predispositions for the development of diseases in later life. Studies in the
      offspring of diabetic mothers have decisively contributed to this perception.
      Alterations of the fetal and neonatal environment which offspring of diabetic
      mothers 'experience' seem to program a disposition to develop obesity, diabetes
      mellitus and Syndrome X-like alterations throughout later life. Underweight at
      birth is also suggested to lead to an increased risk of Syndrome X in later life
      ('Barker hypothesis'). Pathophysiological mechanisms are unclear. Hormones are
      important environment-dependent organizers of the developing neuro-endocrine
      immune network, which finally regulates all fundamental processes of life. When
      present in non-physiological concentrations during 'critical periods' of
      perinatal life, induced by alterations in the intrauterine or neonatal
      environment, hormones can act as 'endogenous functional teratogens'. Perinatal
      hyperinsulinism is pathognomonic in the offspring of diabetic mothers. Early
      hyperinsulinism also occurs as a result of early postnatal overfeeding. In rats,
      endogenous hyperinsulinism, as well as peripheral or only intrahypothalamic
      insulin treatment during perinatal development, may lead to 'malprogramming' of
      neuroendocrine systems regulating body weight, food intake and metabolism. This
      results in an increased disposition to become obese and to develop diabetes
      throughout life. In conclusion, a complex malprogramming of the central
      regulation of body weight and metabolism may provide a general etiopathogenetic
      concept, explaining perinatally acquired dispositions, thereby opening a wide
      field of primary prevention.

PMID- 16280142
TI  - Steroidal saponins from roots of Asparagus officinalis.
AB  - Sarsasapogenin M (1) and sarsasapogenin N (2), two new oligospirostanosides with
      a unique aglycone moiety, (25S)-5beta-spirostan-3beta, 17alpha-diol, along with
      seven known compounds (25S)-5beta-spirostan-3beta-ol-3-O-beta-d-glucopyranosyl
      (1,2)-[beta-d-xylopyranosyl-(1,4)]-beta-d-glucopyranoside (3), (25S)-5beta
      spirostan-3beta-ol-3-O-beta-d-glucopyranosyl-(1,2)-beta-d-glucopyranoside (4),
      (25S)-5beta-spirostan-3beta-ol-3-O-alpha-l-rhamnopyranosyl-(1,2)-[alpha-l
      rhamnopyranosyl-(1,4)]-beta-d-glucopyranoside (5), (25S)26-O-beta-d
      glucopyranosyl-5beta-furost-20 (22)-ene-3beta,26-diol-3-O-beta-d-glucopyranosyl
      (1,2)-beta-d-glucopyranoside (6), yamogenin (7), beta-sitosterol (8), and
      sitosterol-beta-d-glucoside (9) were isolated from the roots of Asparagus
      officinalis L. Their structures were determined by spectral analysis, including
      extensive 1D and 2D NMR experiments.

PMID- 16280143
TI  - Nongenomic actions of aldosterone: physiological or pathophysiological role?
AB  - The actions of aldosterone are usually divided into persistent genomic mediated
      by the classical mineralocorticoid receptor versus acute nongenomic actions.
      Rapid, nongenomic effects of aldosterone have been shown in a variety of tissues,
      although the physiological relevance of these nongenomic actions remains to be
      established. There is now growing evidence that both the nongenomic and genomic
      actions of aldosterone, are mediated via the same classical mineralocorticoid
      receptor, and there is cross talk between the nongenomic and classical actions of
      steroid hormones. Activation of tissue-specific, second messenger pathways may
      contribute to integration of nongenomic and classical actions of aldosterone.
      Further studies are required to determine the physiological or pathophysiological
      role of these nongenomic actions of aldosterone and whether they might amplify
      pathophysiological effects of aldosterone.

PMID- 16280144
TI  - Synthesis and pharmacological evaluations of new steroidal anti-inflammatory
      antedrugs: 9alpha-Fluoro-11beta,17alpha,21-trihydroxy-3,20-dioxo-pregna-1,4-diene
      16alpha-carboxylate (FP16CM) and its derivatives.
AB  - In continuing efforts to develop potent anti-inflammatory steroids without
      systemic adverse effects, methyl 9alpha-fluoro-11beta,17alpha,21-trihydroxy-3,20
      dioxo-pregna-1,4-diene-16alpha-carboxylate (FP16CM) and its 16-alkoxycarbonyl
      derivatives (FP16CE, FP16CP and FP16CB) were synthesized based on the antedrug
      concept. The steroids were evaluated for their pharmacological activities and
      adverse systemic effects. All steroidal antedrugs showed both binding affinity to
      the glucocorticoid receptor in liver cytosol and inhibitory effect on
      lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7
      macrophage cell. These compounds also inhibited croton-oil-induced ear edema and
      showed no systemic effects such as thymus atrophy and suppression of
      corticosterone level after 5-day treatment. Among those compounds tested, FP16CM
      showed the highest activities in receptor binding, NO inhibition and ear edema,
      these activities were comparable to those of prednisolone. Hydrolysis study in
      plasma showed that FP16CB was hydrolyzed rapidly, with the half-live (T1/2) of
      3.2 min and the half-lives of other compounds were between 16.9 and 29.4 min.
      These results support the antedrug concept, of which the decrease in systemic
      adverse effects is attributed to fast hydrolysis to inactive metabolite in the
      systemic circulation.

PMID- 16280145
TI  - 3-Keto steroids from the marine organisms Dendrophyllia cornigera and Cymodocea
      nodosa.
AB  - The new (20R)-22E-cholesta-4,22-diene-3,6-dione (1), along with three known 3
      keto steroids were isolated from the deep-water Mediterranean scleractinian coral
      Dendrophyllia cornigera (2-4). Moreover, four known related 3-keto steroids were
      isolated from the sea grass Cymodocea nodosa (5-8). The structure elucidation of
      steroid 1 and the full NMR resonance assignments of all isolated metabolites were
      based on interpretation of their spectral data. All compounds are reported for
      the first time as metabolites of the investigated organisms. Compounds 2 and 3
      showed significant cytotoxicity against lung cancer NSCLC-N6 cell line.

PMID- 16280147
TI  - Increased hepatotoxicity of acetaminophen in Hsp70i knockout mice.
AB  - The effect of the inducible forms of 70 kDa heat shock protein (Hsp70i) on
      acetaminophen (APAP) hepatotoxicity was assessed in an Hsp70i knockout mouse
      model. Absence of the Hsp70i protein in liver was verified by monitoring Hsp
      levels in knockout and control mice after heat stress (41.5 degrees C water bath
      immersion for 30 min). Hsp70i knockout mice were more susceptible to APAP-induced
      hepatotoxicity than controls, as indicated by elevated serum alanine
      aminotransferase activities 24 and 48 h after the APAP dose. Increased APAP
      hepatotoxicity in knockout mice was verified by morphological evaluation of liver
      sections. The difference in toxic response to APAP between knockout and control
      strain mice could not be attributed to differences in APAP bioactivation,
      assessed by measurement of CYP2E1 and glutathione S-transferase activities,
      hepatic nonprotein sulfhydryl content, or covalent binding of reactive APAP
      metabolites to proteins. Pretreatment with transient hyperthermia to produce a
      general upregulation of Hsps resulted in decreased APAP hepatotoxicity in both
      the knockout and control strains. Among thermally-pretreated mice, hepatotoxicity
      of APAP was greater in the knockouts compared with the control strain. These
      observations suggest that increased Hsp70i expression in response to APAP acts to
      limit the extent of tissue injury. Results further suggest that other factors
      related to heat stress can also contribute to protection against APAP toxicity.

PMID- 16280148
TI  - Aerobic spore-forming bacteria for assessing quality of drinking water produced
      from surface water.
AB  - Cryptosporidium and Giardia represent a major microbiological issue for drinking
      water production from surface water. As their monitoring through a treatment
      process is rather tedious and as low-concentration goals should be reached for
      drinking water, aerobic spore-forming bacteria (ASFB) have been studied as an
      indicator microorganism for a drinking water treatment plant using surface water.
      The results reveal that monitoring naturally occurring ASFB better highlights
      daily achievable performances and identifies unusual process events for global
      disinfection, for both physical and chemical treatment steps in a multi-barrier
      drinking water treatment plant. Advantages of ASFB over usual process parameters
      are that these microorganisms are more sensitive to process fluctuations. The use
      of ASFB also showed that the efficiency of ozone disinfection is not as
      significantly influenced by the water temperature as reported, despite similar or
      higher CT values applied during warmer periods. Thus, the disinfection of
      resistant microorganisms with ozone can also be an efficient process at lower
      water temperature. ASFB have been shown to be a conservative indicator for
      Cryptosporidium and Giardia up to a 1st stage filtration and the ASFB Log
      removals can be used to estimate Log removals for Cryptosporidium and Giardia:
      compared to ASFB, the Log removals for Cryptosporidium or Giardia are at least
      equal or 50% higher, respectively. Thus, the monitoring of ASFB along a drinking
      water treatment process could be a useful tool for performing risk analysis for
      parasites such as Cryptosporidium and Giardia, and would further allow
      integration of daily variability into a risk analysis.

PMID- 16280146
TI  - Developmental changes of serum steroids produced by cytochrome P450c17 in rat.
AB  - Serum levels of 17-hydroxypregnenolone, dehydroepiandrosterone, 17
      hydroxyprogesterone, and androstenedione were measured during the postnatal
      development of rats 1-14 weeks of age. A significant decrease in the serum levels
      of these steroids with increasing age was observed, using multiple regression
      analysis: 17-hydroxypregnenolone (beta= -1.56, S.E.= 0.25, P < 0.00001),
      dehydroepiandrosterone (beta= -0.43, S.E.= 0.07, P < 0.00001), 17
      hydroxyprogesterone (beta= -2.51, S.E.= 0.45, P < 0.00001), and androstenedione
      (beta= -1.63, S.E.= 0.33, P < 0.00001). A sex-related difference was not found.
      The observed decline in the serum levels of the steroids was directly
      proportional to the previously reported decrease in mRNA expression and enzyme
      activity of cytochrome P450c17 in the rat liver. Yet, despite this decrease to
      undetectable levels in liver after 7-8 weeks, significant amounts of 17
      hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, and
      androstenedione were still observed in the rat serum. This may partly be due to
      the mRNA expression of cytochrome P450c17 in tissues other than the liver, such
      as the testis and/or duodenum, after 4 weeks of age. Serum levels of
      pregnenolone, progesterone, and corticosterone in the developing rats were also
      examined.

PMID- 16280149
TI  - Lipophilic organic contaminants in the Rhine river, Germany.
AB  - Detailed gas chromatographic-mass spectrometric analyses applied to eight Rhine
      river water samples constituted a comprehensive characterization of the low
      molecular weight organic contamination. Within the group of predominant
      anthropogenic contaminants, only a few compounds were characterized as frequently
      detected or priority pollutants. Numerous compounds exhibiting physiological or
      ecotoxicological properties are only rarely reported or still unnoticed riverine
      contaminants. Information on environmental behaviour or ecotoxicological effects
      is still limited for most of these substances. In particular, several brominated
      compounds (mono- and dibrominated (methoxyphenyl)propionic acids and
      hydroxymethylacetophenones) were identified for the first time as environmental
      contaminants. Quantitative analyses differentiated five groups of pollutants with
      respect to their concentration profiles. The spatial distribution and the
      intensity of emission sources on the one hand and the environmental stability as
      well as the tendency to adsorb on the particulate matter on the other hand
      determined the quantitative occurrence of individual compounds.

PMID- 16280150
TI  - Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF
      16/FOXO.
AB  - The conserved SIR2 protein regulates life span in both yeast and worms: in both
      organisms overexpression of SIR2 can extend life span and in Caenorhabditis
      elegans this life span extension is dependent on the forkhead transcription
      factor, DAF-16. Here, we have done extensive genetic analysis with sir
      2.1(ok434), a null mutant of C. elegans sir-2.1, the closest homolog to yeast
      Sir2p and human SIRT1 to further elucidate its function in life span regulation.
      sir-2.1(ok434) mutants show a slight decrease in life span as well as sensitivity
      to various stresses. Our genetic analysis suggests that sir-2.1 is required for
      life span extension by caloric restriction, independent of the insulin/IGF-1
      signaling pathway. Importantly, analysis with unc-13 mutants indicates that sir
      2.1 and daf-16 have overlapping and distinct roles in life span regulation. Our
      expression analysis shows that sir-2.1 has overlapping and distinct expression
      pattern compared with daf-16, consistent with the results from our genetic data.
      Our data defines a central role for C. elegans SIR2 in regulation of life span by
      caloric restriction and demonstrates that sir-2.1 and daf-16 have both
      overlapping and distinct functions in regulation of C. elegans life span.

PMID- 16280151
TI  - Cognitive rehabilitation for severe dementia: critical observations for better
      use of existing knowledge.
AB  - Cognitive rehabilitation for severely demented patients is a hard job for a
      number of reasons. The most recent evidence-based strategies (such as the cued
      recall or the spaced retrieval techniques) aim to improve cognitive function at
      initial stages of the disease, while in more severe stages interventions such as
      validation therapy are used, which are traditionally adopted, but lack a solid
      scientific rationale, and often even a consistent evidence-based efficacy. Many
      studies have been carried out to try demonstrate the effect of these "therapies",
      or to project new interventions, while little attention has been given to the
      fact that simple neuropsychological principles keeping into account the nature of
      the pathological aging observed in dementia can be fruitfully adopted to improve
      and personalize different kinds of intervention. A rational use of current
      neuropsychological concepts optimizes the patient's benefit as well as the
      operator's efforts. A rehabilitative intervention based on current
      neuropsychological concepts and on awareness of the mechanisms of pathological
      ageing of cognition provides the possibility of tailored treatments for many
      different patients, an important reduction of burn-out in the personnel, and
      clinically relevant outcomes, such as an implicit orientation for the patient,
      with beneficial effects on mood and behavior.

PMID- 16280152
TI  - Quantification of the effects of environmental leaching factors on emissions from
      bottom ash in road construction.
AB  - The re-use of bottom ash in road construction necessitates a tool to predict the
      impact of trace metals on the surroundings over the lifetime of the road. The aim
      of this work was to quantify the effect of environmental factors that are
      supposed to influence leaching, so as to suggest guidelines in developing a
      leaching procedure for the testing of incineration residues re-used in road
      constructions. The effects of pH, L/S (liquid-to-solid ratio), leaching time, and
      leaching atmosphere on the leachate concentrations of Cd, Cr, Cu, Ni, Pb, and Zn
      were studied using a two-level full factorial design. The most significant factor
      for all responses was the pH, followed by L/S, though the importance of pH and
      L/S is often ignored in leaching tests. Multiple linear regression models
      describing the variation in leaching data had R(2) values ranging from 61-97%. A
      two-step pH-stat leaching procedure that considers pH as well as L/S and leaching
      time was suggested.

PMID- 16280153
TI  - Contribution of trona (magadi) into excessive fluorosis--a case study in Maji ya
      Chai ward, northern Tanzania.
AB  - Excessive fluoride ingestion predominantly comes from drinking water sources.
      However, prevalence and severity of dental and skeletal fluorosis in northern
      Tanzania have been reported to be higher than would be expected from ingestion of
      fluoride through drinking water alone. This study aimed at investigating the
      contribution of "trona" (also locally known as magadi) a food additive, to the
      prevalence and severity of fluorosis in northern Tanzania. The study was carried
      out in four villages (Embaseni, Kitefu and Ngurdoto) in Maji ya Chai ward; and
      Nkoanekoli in Poli ward, in Arusha region, Tanzania. Analysis of fluoride
      concentrations was carried out in drinking water sources as well as in magadi
      samples. Assessment of the prevalence of dental fluorosis using Dean's Index
      Method was carried out for a population of 2217 pupils in four primary schools
      located in the case study area. Fluoride concentration in drinking water sources
      was found to range from 1.7 to 11.3 mg/l, while the concentration in magadi
      samples in case study villages were in the range of 0.21 to 0.9 mg/g. Total
      fluoride ingestion through magadi and water were established to be 11.74
      mg/person/day in Embaseni, 36.1 mg/person/day in Ngurdoto, 10.88 mg/person/day in
      Kitefu and 5.7 mg/person/day in Nkoanekoli villages. Levels of total fluoride
      ingestion were directly correlated with Community Fluorosis Index (CFI) values,
      which were found to be 3.32 (in Embaseni), 3.67 (in Ngurdoto), 2.2 (in Kitefu)
      and 1.47 (in Nkoanekoli). The village with the highest fluoride consumption rate
      showed the highest CFI as well. High levels of fluoride concentrations in magadi
      suggest that excessive fluorosis in northern Tanzania may be due to the use of
      magadi in food preparations.

PMID- 16280154
TI  - Circulating matrix metalloproteinase-9 levels and alteplase treatment.

PMID- 16280155
TI  - The impact of chromosomal alteration on embryo development.
AB  - Chromosome alterations, such as those affecting telomere erosion, predictably
      occur with each cell division, others, which involve changes to the expression
      and replication of the X-chromosome occur at particular stages of development,
      while those that involve loss or gain of chromosomes occur in a random and so far
      unpredictable manner. The production of embryos in vitro and by somatic cell
      nuclear transfer (SCNT) has been associated with altered expression of marker
      genes on the X-chromosome and an increased incidence of chromosomally abnormal
      cells during early development. In the case of SCNT embryos chromosome
      abnormalities may be associated with the nuclear donor cell. Telomere rebuilding
      subsequent to SCNT appears to vary according to species and type of donor cell
      used. It is speculated that the rate of telomere erosion and incidence of
      chromosome abnormalities affects developmental potential of early embryos and may
      be potential predictors of developmental outcome.

PMID- 16280156
TI  - Strategies for improving fertility in the modern dairy cow.
AB  - The high producing dairy cow of the 21st century is subfertile during lactation.
      Our objectives are to characterize physiological periods limiting reproductive
      performance and to describe integrated management strategies to improve pregnancy
      rates. Ovarian recrudescence with normal re-occurring estrous cycles and
      restoration of fertility to first service are associated with a reduced
      occurrence of periparturient metabolic and reproductive disorders. Marked
      negative changes in energy balance and reduced immunocompetence influence
      gonadotropic and metabolic hormones. Induced ovarian inactivity was associated
      with enhanced uterine involution. Post-partum health and reproductive performance
      were improved when by-pass lipids enriched in polyunsaturated fatty acids were
      fed in the pre- and post-partum periods. Pharmaceutical control of follicle, CL,
      and uterine function with PGF, GnRH and intravaginal progesterone releasing
      inserts, has permitted development of more optimal timed-insemination programs
      for first service. Likewise, resynchronization of nonpregnant cows coupled with
      the use of ultrasound for early pregnancy diagnosis provides the opportunity for
      a second timed-insemination within 3 days of a nonpregnant diagnosis. Bovine
      somatotropin (bST) increases embryo development and embryo survival when coupled
      with a timed-insemination program or cows detected in estrus. Presence of a
      conceptus alters endometrial expression of genes and proteins in response to bST
      and nutraceuticals (i.e., unsaturated fatty acids such as eicosapentaenoic and
      docosahexaenoic acid in by-pass lipids) to improve pregnancy rates. Postovulatory
      increases in progesterone may enhance pregnancy rates in targeted populations of
      lactating dairy cows, but timing and magnitude of the progesterone increases are
      pharmaceutically dependent.

PMID- 16280159
TI  - Is apoptosis in bovine in vitro produced embryos related to early developmental
      kinetics and in vivo bull fertility?
AB  - Although several studies have indicated a paternal effect on bovine embryo
      development, no conclusive data exist on the effect of in vivo bull fertility on
      apoptosis. Therefore, it was the main objective of this study to compare the
      apoptotic cell ratio (ACR) in embryos originating from bulls with different in
      vivo fertility. However, since it is has been demonstrated before that bulls with
      different in vivo fertility differ in timing of first cleavage, it was necessary
      to investigate first the effect of timing of development on apoptosis in vitro in
      order to get an unbiased insight in the contribution of in vivo bull fertility on
      apoptosis in bovine blastocysts. In the first experiment, bovine embryos (n =
      939) were allocated to different groups according to cleavage rate at 30, 36 and
      48 hpi and blastocysts were selected at 7 and 8 dpi. The blastocyst rate at 7 dpi
      was significantly lower in embryos which had first cleaved at 48 hpi than in
      embryos from the 30 and 36 hpi group (P < 0.05). The ACR after TUNEL in day 7
      blastocyst was significantly lower in the 30 hpi group in comparison with the 36
      and 48 hpi group (P < 0.05) and lower in day 7 blastocysts than in day 8
      blastocysts. In the second experiment, sperm of eight bulls with different non
      return rates was used for in vitro bovine embryo production (n = 3820 oocytes).
      Cleavage rates (30, 36 and 48 hpi) and blastocyst rate (7 dpi) were determined.
      Only very low negative correlations could be found between in vivo and in vitro
      bull fertility and ACR did not differ between groups derived from sires with
      either low or normal fertility (P > 0.05). Further research in serum free
      conditions is needed to confirm that the lower ACR in early cleaved embryos could
      be mediated by the cooperative interaction of embryos of good quality cultured in
      group. In vivo bull fertility could hardly be correlated with in vitro blastocyst
      yield and could not be correlated with appearance of apoptosis.

PMID- 16280157
TI  - Embryo technologies and animal health - consequences for the animal following
      ovum pick-up, in vitro embryo production and somatic cell nuclear transfer.
AB  - Mammalian reproductive technologies that aim either to complement or to transcend
      conventional livestock breeding options have contributed to some of the most
      remarkable achievements in the field of reproductive biology in recent decades.
      In so doing they have extended our horizons in two distinct dimensions, the first
      concerning what it is technically possible to achieve and the second relating to
      the time-frame within which an individual's life-long developmental capability is
      initially established and ultimately realized or undermined. Our impressions of
      the benefits and values, or otherwise, of technologies such as in vitro embryo
      production and nuclear transfer are rightly influenced by the extent to which
      they impinge on the health of animals either subjected to or derived from them.
      Here, we consider some of the health implications of oocyte/embryo-centric
      technologies applied to farm livestock.

PMID- 16280160
TI  - Prevalence of chlamydiae in boars and semen used for artificial insemination.
AB  - Although there are indications for venereal transmission of chlamydiae in pigs,
      direct diagnostic evidence on the presence of these bacteria in boars and boar
      semen in particular is still incomplete. We investigated boars from two studs (A,
      B) in semen (A: n = 174; B: n = 100) and faeces (A: n = 174; B: n = 24) for
      chlamydiae using ompA-PCR and partial ompA gene sequencing. Additionally, blood
      serum was examined for chlamydial antibodies using an indirect ELISA (A: n = 171;
      B: n = 62). Chlamydiae were found in 9 (5.2%) and 24 (24.0%) semen specimens, and
      in 71 (40.1%) and 2 (8.3%) faecal samples from boars of stud A and B,
      respectively. Regarding individual chlamydial species, Chlamydophila psittaci and
      Chlamydia suis were identified most frequently, with the former predominating in
      semen (in 23 out of 33 positive samples) and the latter in faeces (68/73). In
      contrast, Chlamydophila pecorum was found only sporadically. Chlamydial
      antibodies were detected in 80 (46.8%) and 6 (9.7%) boars of stud A and B,
      respectively. No correlation was observed between the data from serology and PCR
      of semen or faeces in either of the studs. In conclusion, detection of chlamydiae
      in semen of boars suggests a potential for venereal transmission. Whether the
      high overall prevalence of chlamydial infections reflects a general situation in
      boars needs to be investigated. Serological testing failed to identify boars
      shedding chlamydiae in their semen.

PMID- 16280161
TI  - Sub-cellular accumulation of magnetic nanoparticles in breast tumors and
      metastases.
AB  - In this study, the sub-cellular accumulation of superparamagnetic iron oxide
      nanoparticles (SPIONs) in breast tumors and peripheral organs were investigated.
      MNPs were conjugated with luteinizing hormone releasing hormone (LHRH), whose
      receptors are expressed by most types of breast cancer cells. After the
      nanoparticles were injected into female nude mice bearing MDA-MB-435S.luc tumors,
      the mice were sacrificed to collect tumors and peripheral organs for biological
      and TEM analyses. LHRH conjugated SPIONs (LHRH- SPIONs) were found to accumulate
      in cancer cells, mainly in the primary tumors and the metastatic lungs, where
      they aggregated to form clusters. In contrast, most of the unconjugated SPIONs
      were collected in the liver cells. The results suggest that LHRH- SPIONs can be
      used to target cancer cells in the primary breast tumors and the lung metastases.
      TEM is also shown to be a useful tool for the studies of sub-cellular
      distributions of SPIONs in tumors and tissues.

PMID- 16280162
TI  - Pesticide exposure and lung cancer mortality in Leningrad province in Russia.
AB  - This study was carried out to examine the association between pesticide exposure
      and lung cancer mortality. We conducted an autopsy based case-control study in
      Leningrad Province in Russia. A total of 540 lung cancer cases and 582 controls
      were identified among subjects who had died in the hospitals of the Leningrad
      province between 1993 and 1998. Using work history records, we assessed exposure
      to pesticide at the level of industry and job title. Unconditional logistic
      regression was used to calculate adjusted odds ratio for pesticide exposure and
      lung cancer mortality. There was no association between ever exposure to
      pesticide and lung cancer mortality overall (odds ratio=1.06, 95% confidence
      interval=0.82-1.36) and in both men (odds ratio=1.11, 95% confidence
      interval=0.84-1.46) and women (odds ratio=0.74, 95% confidence interval=0.37
      1.46). We observed no statistically significant odds ratio by duration of
      pesticide exposure, intensity of pesticide exposure, and cumulative pesticide
      exposures with lung cancer mortality in both smokers and nonsmokers. Odds ratio
      also did not differ when the analysis was restricted to individuals who had
      exposure data with high confidence scores. Our findings suggest no associations
      between pesticide exposures and mortality of lung cancer in the population of the
      Leningrad province in Russia that deserves further evaluation.

PMID- 16280163
TI  - Exchange of polycyclic aromatic hydrocarbons across the air-water interface at
      the creek adjoining Mumbai harbour, India.
AB  - Concentration levels of polycyclic aromatic hydrocarbons (PAHs) have been
      determined in air and water in order to estimate the magnitude and direction of
      gas flux across the air-water interface at the creek adjoining the Mumbai
      harbour, India. The range of total PAHs was found to be 4.1-30.4 ng/m3 in air and
      84.3-377.5 ng/l in seawater, respectively. The lower molecular weight PAHs
      revealed positive values of the fluxes indicating the tendency for transfer of
      these contaminants from water to air. In contrast, fluxes of less volatile
      compounds like benzo(k)fluoranthene and benzo(a)pyrene were always from the
      atmosphere into the surface water of the creek at all locations and sampling
      periods. While the fugacity ratio ranged from 0.12 to 6.97, it was found greater
      than 1 for the lower molecular weight PAHs and less than 1 for higher molecular
      weight PAHs. The present study suggests the active transfer of lower molecular
      weight dissolved PAHs into the atmosphere due to volatilization and deposition of
      higher molecular weight gas-phase PAHs into the surface water.

PMID- 16280164
TI  - Identification of peptide ligands to the chemokine receptor CCR5 and their
      maturation by gene shuffling.
AB  - The determination of protein-protein interactions and their role in diverse
      pathophysiological processes is a promising approach to the identification of
      molecules of therapeutic potential. This paper describes the identification of
      peptidic CCR5 receptor ligands as potential drug leads against HIV-1 infection
      using in vitro evolution based on phage display. A phage-displayed peptide
      library was used to select for anti-CCR5 peptide. Further in vitro evolution of
      the peptide by exon shuffling was performed to identify peptides with optimized
      characteristics for CCR5 receptor. This peptide inhibited HIV coreceptor activity
      in a cell fusion assay with an IC50 of 5 microM. It did not exhibit either
      agonistic or antagonistic activity on CCR5 in the concentration range used. To
      our knowledge, this is a first report that describes the identification of
      peptide ligands specific to the CCR5 receptor from a phage-displayed library and
      the maturation of the selected peptide sequence by gene shuffling.

PMID- 16280165
TI  - Genomic organization, gene duplication, and expression analysis of interleukin
      1beta in channel catfish (Ictalurus punctatus).
AB  - Interleukin-1beta (IL-1beta) is one of the pivotal early response pro
      inflammatory cytokines that enables organisms to respond to infection and induces
      a cascade of reactions leading to inflammation. In spite of its importance and
      two decades of studies in the mammalian species, genes encoding IL-1beta were not
      identified from non-mammalian species until recently. Recent research,
      particularly with genomic approaches, has led to sequencing of IL-1beta from many
      species. Clinical studies also suggested IL-1beta as an immunoregulatory molecule
      potentially useful for enhancing vaccination. However, no IL-1beta genes have
      been identified from channel catfish, the primary aquaculture species from the
      United States. In this study, we identified two distinct cDNAs encoding catfish
      IL-1beta. Their encoding genes were identified, sequenced, and characterized. The
      catfish IL-1beta genes were assigned to bacterial artificial chromosome (BAC)
      clones. Genomic studies indicated that the IL-1beta genes were tandemly
      duplicated on the same chromosome. Phylogenetic analysis of various IL-1beta
      genes indicated the possibility of recent species-specific gene duplications in
      channel catfish, and perhaps also in swine and carp. Expression analysis
      indicated that both IL-1beta genes were expressed, but exhibited distinct
      expression profiles in various catfish tissues, and after bacterial infection
      with Edwardsiella ictaluri.

PMID- 16280166
TI  - TLR3 activation inhibits human mast cell attachment to fibronectin and
      vitronectin.
AB  - Mast cells are involved in both the genesis of allergic inflammation and in host
      defense; and reside in tissues where their location and responsiveness is
      regulated in part by adhesion to extracellular matrix proteins (ECM). We have
      reported that human mast cells (huMC) express TLR1-7, and 9 and respond to toll
      like receptors (TLR) ligands by releasing cytokines and leukotriene C4. To
      determine if TLR ligation could similarly affect mast cells via an influence on
      adhesion, we employed huMC; and as substrates, fibronectin (FN) and vitronectin
      (VN). huMC were thus treated with double-stranded RNA (dsRNA) and adhesion to ECM
      was quantified. FcvarepsilonRI dependent mast cell degranulation was assessed.
      Adhesion molecule expression and activation was measured by flow cytometry.
      Activation of huMC through TLR3 with increasing amounts of polyI:C inhibited mast
      cell adhesion in a dose-dependent manner. This decrease in adhesion was
      accompanied by a similar decrease in IgE-mediated mast cell degranulation.
      Activation of TLR3 on huMC resulted in a change in the conformation of CD29, the
      receptor for FN, to an inactive form. Thus, TLR3 activation decreases mast cell
      attachment to VN and FN through an active process and one, which would abrogate
      mast cell attachment dependent potentiation of IgE-mediated responses.

PMID- 16280167
TI  - Display and selection of chicken IgA Fab fragments.
AB  - Passive immune therapy is regaining interest to prevent and cure infectious
      diseases both in human and veterinary medicine. Therefore, systems are required
      that enable efficient targeted selection of antibodies originating from virtually
      any animal species. Here, a system for the selection of chicken IgA, using phage
      display, is described. A novel phagemid vector (pChick3) for the display and
      selection of chicken IgA antibodies in Fab format was developed. The
      functionality of pChick3 was demonstrated by construction of an immune antibody
      library using B cells from chickens infected with Eimeria acervulina. From this
      library, 10 different IgA fragments with specific binding to the E. acervulina
      antigen mix, the sporozoite or oocyst fractions were selected. These results
      demonstrate the efficiency and versatility of the pChick3 vector system that can
      readily be applied to construct libraries and subsequently select antibodies of
      the alpha isotype against a wide variety of pathogens and parasites.

PMID- 16280169
TI  - Long-lived plasma cells in immunity and immunopathology.
AB  - Following tetanus vaccination, a wave of antibody-secreting cells appear in the
      peripheral blood composed of vaccine-specific, migratory plasmablasts and plasma
      cells secreting antibodies specific for other antigens. The latter probably were
      tissue resident plasma cells formed in earlier immune responses that are
      mobilized due to competition with the newly formed tetanus-specific plasmablasts.
      Newly formed plasma cells secreting antibodies specific for a particular
      antigen/vaccine are accommodated in the bone marrow likely at the global expense
      of the pre-existing long-lived plasma cell population providing humoral memory
      for other antigens. Plasmablasts but not mature plasma cells are attracted by the
      ligands for the chemokine receptors CXCR4 and CXCR3. While CXCR4 and its cognate
      ligand is important for plasma cell homing to the bone marrow, CXCR3 and its
      ligand IP10 are likely to be involved in attracting them to inflamed tissue. In
      NZB/W mice, a model for systemic lupus, long-lived autoreactive plasma cells are
      present not only in bone marrow, but also in inflamed tissues and spleen.
      Autoreactive plasma cells in the spleen are present long before the onset of the
      disease, suggesting that these cells contribute to induction of immunopathology.

PMID- 16280168
TI  - Inhibition of interleukin-4 production in activated T cells via down-regulation
      of NF-AT DNA binding activity by apigenin, a flavonoid present in dietary plants.
AB  - Apigenin, a flavonoid present in many dietary plants, exhibits anti-allergic
      activity and inhibits IL-4 production by basophils and mast cells. However, the
      mechanism by which apigenin suppresses IL-4 production especially in T cells
      remains unclear. In this study, the effect of apigenin and its underlying
      mechanism on IL-4 production were investigated in activated T cells. Apigenin
      significantly inhibited IL-4 production in both EL4 T thymoma cells and primary
      lymph node cells. Apigenin also inhibited IL-4 gene promoter activity in EL4
      cells transiently transfected with IL-4 gene promoter constructs, but this
      inhibitory effect was impaired in EL4 cells transfected with an IL-4 promoter
      construct deleted of NF-AT binding sites. In addition, apigenin inhibited NF-AT
      DNA binding activities, indicating that apigenin may inhibit IL-4 production in T
      cells via down-regulation of NF-AT DNA binding activity.

PMID- 16280170
TI  - The face does predict the brain--midline facial and forebrain defects uncovered
      during the investigation of nasal obstruction and rhinorrhea. Case report and a
      review of holoprosencephaly and its classifications.
AB  - When the embryonic forebrain (the prosencephalon) fails to sufficiently divide
      into the two cerebral hemispheres, holoprosencephaly (HPE) results. This disorder
      can result in various skull and facial defects with brain abnormalities of
      varying severity. These brain defects ultimately dictate the prognosis. This
      varies from death in utero, to normal or near normal brain development. In these
      less severe cases, otherwise normally developing babies are born with rarely seen
      midfacial cleft deformities, giving away a structural brain deformity. We report
      a case of an otherwise developmentally normal seven-year-old boy who was being
      assessed for nasal obstruction and rhinorrhea. Investigation directed by a high
      index of suspicion uncovered an occult case of holoprosencephaly.

PMID- 16280171
TI  - Foreign body aspiration: clinical, radiological findings and factors associated
      with its late removal.
AB  - OBJECTIVE: The study was carried out to assess the clinical and radiological
      findings and factors related to delay in definite diagnosis of foreign body
      aspiration and its removal. METHODS: Medical charts of 280 bronchoscopic-proven
      foreign body (FB) inhalators were reviewed. To analyze factors related to late
      removal, the population studied was divided into two groups according to time
      elapsed between injury and care-seeking (up to 24h and longer than 24h) followed
      by FB removal. RESULTS: Most children (69.5%) were under three, most were males
      (63.1%) and in 47.5%, rigid bronchoscopy was performed 24h after the accident.
      Organic foreign bodies were found in 63.4% of cases, most frequently peanuts
      (20.5%). Mortality related to FB aspiration reached 0.7%. In comparison with
      endoscopic diagnosis, clinical and radiological abnormalities were found in 99.3
      and 84.3% (95% CI, 79.5-88.4%) of studied patients, respectively. The number of
      health services sought until definite diagnosis was the only factor associated
      with late removal (OR=23.0, 95% CI, 10.7-49.3%, p<0.001). CONCLUSION: The
      population studied presented a long delay in FB removal, thus demanding actions
      enhancing parent, physician and health services awareness, aiming at an earlier
      referral for diagnostic and therapeutic bronchoscopy.

PMID- 16280172
TI  - Prolonged diplopia following sinus vein thrombosis mimicking Gradenigo's
      syndrome.
AB  - We report about a boy with the symptoms of Gradenigo's syndrome (abducens nerve
      palsy, acute otitis media, unilateral headache). The MR imaging showed a sinus
      vein thrombosis instead of the expected petroapicitis. After 2 weeks of
      conservative therapy with antibiotics and anticoagulation, without any clinical
      effort the boy underwent a mastoidectomy. Headache and otitis media recovered
      quickly but the diplopia still remained after 25 months.

PMID- 16280173
TI  - The KTP laser: an emerging tool in pediatric otolaryngology.
AB  - PURPOSE: To report the frequency and spectrum of use of the potassium titanyl
      phosphate (KTP) laser in a tertiary referral pediatric otolaryngology practice
      and to focus on a novel use for the KTP laser which has not previously been
      described in the literature. DESIGN: A retrospective chart review of the
      operative log database of a pediatric otolaryngologist in a tertiary referral
      setting over a seven year period. RESULTS: Out of 2886 cases, a total of 49
      (1.7%) involved the use of the KTP laser. These included 7 otologic cases, 3
      laryngeal cases, 31 subglottic/tracheal cases, 1 esophageal case and 7 nasal
      cases. One of these cases involved a previously unreported use of the KTP laser,
      closure of a tracheo-esophageal fistula (TEF). CONCLUSION: The KTP laser is an
      important operative tool in pediatric otolaryngology and new uses for this laser
      continue to emerge. One of these, KTP closure of a TEF offers pediatric
      otolaryngologists the potential for significant changes in management of this
      congenital problem with reduced surgical morbidity. Familiarity with the KTP
      laser and expertise in its use and applications is essential in providing state
      of-the-art care to pediatric otolaryngology patients in a tertiary referral
      center.

PMID- 16280174
TI  - Three extraordinary complications of adenotonsillectomy.
AB  - In a 6-month period, three patients aged 5-11 years were transferred to our
      tertiary care children's hospital for management of severe complications
      following adenotonsillectomy. The first patient presented with headaches and
      lethargy and was found to have a sagittal sinus thrombosis from severe
      dehydration. The second patient was admitted immediately following an intra
      operative oral cavity fire due to electrocautery malfunction. She suffered
      partial-thickness burns to the buccal mucosa, palate, and lips. The third patient
      was admitted with torticollis. Grisel's syndrome was initially suspected, but a
      thorough work up resulted in the diagnosis of a conversion disorder. These cases
      comprise an interesting cohort of three little-known complications of
      adenotonsillectomy.

PMID- 16280175
TI  - Detection and differentiation of human hepatitis A strains by commercial
      quantitative real-time RT-PCR tests.
AB  - Performance characteristics of two commercial quantitative Hepatitis A virus
      (HAV) RT-PCR assays, the LightCycler Hepatitis A virus quantification kit (Roche
      Diagnostics) and the RealArt HAV LC RT PCR kit (artus GmbH) for detection and
      quantification of HAV were evaluated. Both assays rely on reverse transcription
      and amplification of extracted RNA. Dilutions of two HAV strains, belonging to
      different subtypes, were prepared to determine the precision, accuracy, linearity
      and the detection limit. Both assays were found to be suitable for quantification
      measurement of HAV RNA, but only the Roche kit was able to distinguish the
      different HAV strains tested. The linear range for the artus assay was 10(4)
      10(6)IU/ml and 2 x 10(4) to 2 x 10(8) RNA copies/ml for the Roche assay. The
      detection limit of Roche kit was 2 TCID(50)/ml or 500 RNA copies/ml and 5
      TCID(50)/ml or 50 IU/ml for the artus kit. Despite these small differences it is
      concluded that both assays are very suitable for detection and quantification of
      most prevalent HAV subtypes.

PMID- 16280176
TI  - A novel inhibitor of respiratory syncytial virus isolated from ethnobotanicals.
AB  - A novel low molecular weight compound, CJ 4-16-4, isolated from ethnobotanicals
      using bioassay-guided fractionation, was found to be a potent inhibitor of
      respiratory syncytial virus (RSV) in vitro and in vivo. In vitro, a very low
      micromolar efficacious dose was obtained against at least four of subtype A (RSV
      Long, RSV A2, and RSV A6 57754) and one of subtype B (Washington) RSV strains
      without seeing any significant cytotoxicity to Hep-2, MDCK or Vero cell lines.
      The drug inhibits growth of RSV in Hep-2 cells maintained in tissue culture at a
      very low concentration (approximately 0.07 microM) with cell toxicity >400 microM
      (TI>5880). In a cotton rat model of RSV infection, the drug was able to reduce
      viral titers by approximately 1 log at dose 12.5 and 25 mg/kg/day, and by >2 log
      at 100 mg/kg/day. This antiviral activity was specific as influenza A and B and
      herpes simplex 1 and 2 viruses were not inhibited. The results obtained indicate
      that CJ 4-16-4 warrants clinical development.

PMID- 16280177
TI  - Antiviral therapeutic efficacy of foscarnet in hepatitis B virus infection.
AB  - Foscarnet (PFA), a viral DNA polymerase inhibitor, is a clinical agent for herpes
      viruses. The goal of the study was to evaluate the therapeutic efficacy of PFA in
      hepatitis B virus (HBV) infection. Intravenous infusion of PFA (1 g/day) for 4
      weeks significantly reduced serum HBeAg (p<0.01) and HBV DNA copies (p<0.05) in
      31 patients who were diagnosed with active chronic HBV infection (CHB) and had
      not received antiviral treatment previously. Alanine aminotransaminase (ALT),
      aspartate aminotransaminase (AST) and gamma glutamyl transpeptidase (gamma-GT) of
      the patients declined (p<0.001, 0.001 and 0.01, respectively). Kidney function
      (blood creatinine and urea nitrogen) remained unchanged. Another 21 lamivudine
      resistant CHB patients with mutations at the tyrosine-methionine-aspartate
      aspartate motif (YMDD) displayed a response to PFA similar to that mentioned
      above, with reductions in HBeAg (p<0.05), HBV DNA (p<0.01) and liver enzymes (ALT
      and AST, p<0.001; gamma-GT, p<0.05). Moreover, PFA reduced serum HBeAg (p<0.01),
      HBV DNA (P<0.05), AST (p<0.05) and ALT (p<0.02) in a cohort of 13 severe CHB
      patients with advanced liver damage. PFA was also evaluated in vitro and in vivo.
      PFA inhibited HBV DNA replication in HBV-transfected human HepG2 cells (2.2.15
      cells) with reduced amount of HBV RC-DNA and DS-DNA. In the duck HBV-infected
      ducklings, PFA reduced viral DNA and duck HBsAg in the serum (p<0.01 for both).

PMID- 16280178
TI  - Cyclic nucleotide specific phosphodiesterases of the kinetoplastida: a unified
      nomenclature.

PMID- 16280179
TI  - Somatostatin receptors (sst2) regulate cGMP production in rat retina.
AB  - The present study investigated the effect of somatostatin in the regulation of
      cGMP levels in rat retina and the mechanisms involved in this process. Isolated
      rat retinas were treated alone or in the presence of somatostatin (0.01-10
      microM), BIM23014 (sst2 agonist, 0.01-10 microM), L-796,778 (sst3 agonist, 10
      microM), somatostatin (0.1 microM) in combination with CYN154806 (sst2
      antagonist, 1 microM), N(G)-methyl-L-arginine acetate salt (NMMA, inhibitor of
      the nitric oxide synthase (NOS), 250 microM), orthovanadate (inhibitor of
      tyrosine phosphatase, SHP-1, 1 microM), and arginine alone (250 microM). cGMP
      levels were quantified by ELISA. Immunohistochemistry studies were performed for
      the detection of cGMP and nNOS, while Western blot analysis was employed for the
      detection of SHP-1. Somatostatin increased cGMP levels in a concentration
      dependent manner. This increase was inhibited by CYN154806. BIM23014 increased
      cGMP levels only at the concentration of 10 microM, while L-796,778 had no
      effect. NMMA blocked completely the somatostatin stimulated increase of cGMP
      levels and nNOS was detected in rat retina. cGMP immunoreactivity was observed
      primarily in bipolar cells only of nitroprusside-treated retinas. SHP-1
      inhibition by orthovanadate reduced the somatostatin effect in a statistically
      significant manner. These results suggest that a SRIF/SHP-1/NO/cGMP mechanism
      underlies the actions of somatostatin in the retina and in its influence of
      retinal circuitry.

PMID- 16280180
TI  - The chromogranin-A (CgA) in prostate cancer.
AB  - Prostate cancer is one of the most frequent tumors in men. The neuroendocrine
      differentiation in prostate cancer has become more widely recognized and has
      attracted considerable attention as a potentially new finding with major
      diagnostic, prognostic and therapeutic implications. We investigated the role of
      the serum concentrations of CgA in a group of 57 patients with prostate cancer
      and in 61 elderly subjects with benign prostate hyperplasia (BPH). Neuron
      specific enolase (NSE) is the most frequently employed marker to detect
      neuroendocrine features. Serum prostate-specific antigen (PSA), CgA and NSE
      levels were determined. Comparing prostate cancer group versus BPH group, the CgA
      level difference was 63.00 ng/ml (p<0.0001) and the PSA level difference was
      50.86 mcg/ml (p<0.0001). Between prostate cancer group and control group the CgA
      level difference was 94.3 ng/ml (p<0.0001), the PSA level difference was 52.91
      mcg/ml (p<0.0001), and the NSE level difference was 1.34 microg/l (p<0.0001).
      Patients with higher CgA levels had poorer prognosis and survival, compared to
      those with lower CgA levels. These results support the concept that serum CgA
      level determination before treatment is a potential prognostic factor for
      prostate cancer.

PMID- 16280181
TI  - The effects of outpatient co-payment policy on healthcare usage by the elderly in
      Taiwan.
AB  - Aging and declining health are intrinsically related and are resulting in
      increasing healthcare spending in many countries. Control of healthcare spending
      and patient usage behavior are linked. This study examines the healthcare usage
      behavior of chronically ill elderly patients in Taiwan following an increase in
      co-payments. The differences in usage behavior are interpreted by comparing the
      frequency of hospital visits and the types of hospitals chosen by patients before
      and after the implementation of the new co-payment policy. Claim data of the
      Taipei branch of the National Health Insurance Bureau (NHIB) is used as a basis
      for this analysis. Analysis results indicate that choice of hospital type by the
      elderly is affected by an increase in co-payment, but that difference of the
      hospital type choice before and after the co-payment increase is too small to be
      practically significant. However, the frequency of visits decreased significantly
      after the implementation of the new co-payment policy. Medical care costs per
      visit for individual patients and for the National Health Insurance system both
      increased significantly. Visit frequency and hospital type choice, as well as
      diagnosis and treatment cost and co-payment, all show significant differences
      among different age groups of the elderly. The effects of co-payment increases
      are also discussed from the viewpoint of patients and of governmental policy.

PMID- 16280182
TI  - Direct to consumer advertising in pharmaceutical markets.
AB  - We study effects of direct-to-consumer advertising (DTCA) in the prescription
      drug market. There are two pharmaceutical firms providing horizontally
      differentiated (branded) drugs. Patients differ in their susceptibility to the
      drugs. If DTCA is allowed, this can be employed to induce (additional) patient
      visits. Physicians perfectly observe the patients' type (of illness), but rely on
      information to prescribe the correct drug. Drug information is conveyed by
      marketing (detailing), creating a captive and a selective segment of physicians.
      First, we show that detailing, DTCA and price (if not regulated) are
      complementary strategies for the firms. Thus, allowing DTCA induces more
      detailing and higher prices. Second, firms benefit from DTCA if detailing
      competition is not too fierce, which is true if investing in detailing is
      sufficiently costly. Otherwise, firms are better off with a ban on DTCA. Finally,
      DTCA tends to lower welfare if insurance is generous (low copayments) and/or
      price regulation is lenient. The desirability of DTCA also depends on whether or
      not the regulator is concerned with firms' profit.

PMID- 16280183
TI  - Vancomycin-resistant enterococci (VRE) in meat and environmental samples.
AB  - We investigated the spread of vancomycin-resistant enterococci (VRE) in strains
      from meat and environmental samples and the location of glycopeptide-resistance
      determinants in VanA isolates. VRE and VSE (vancomycin-sensitive enterococci)
      resistance patterns to six antimicrobials were also evaluated. A total of 59 meat
      isolates (35%) and 119 environmental isolates (26.5%) were glycopeptide resistant
      enterococci. In particular, 10.7% meat isolates belonged to the VanA, 8.3% to
      VanB and 16% to VanC phenotypes. Environmental samples presented 0.7% VanA, 14.5%
      VanB, and 11.4% VanC strains. Evident differences were not observed among the
      resistance patterns of VRE and VSE isolates. Neither an important difference was
      observed comparing the resistance patterns in enterococci from meat and
      environment. In particular a low incidence of beta-lactamic resistant strains was
      found, whereas high rates of resistance were observed for streptomycin (85.7% and
      92.8%), kanamycin (79.7% and 96%) and gentamycin (85.1% and 91.7%). An
      intermediate rate of resistant bacteria emerged for erythromycin (35.1% and
      10.5%). All VanA isolates independent of origin had more plasmids with different
      molecular weights. PCR amplification of the 732 bp fragment in plasmids from the
      VanA strains confirmed affiliation to the vanA gene cluster and the
      extrachromosomal location of the glycopeptide-resistance determinants. Our study
      suggests that food and environment play a potential role as reservoirs of
      resistance determinants, prompting the need to undertake epidemiological and
      molecular studies to evaluate the mobility of these genes.

PMID- 16280184
TI  - A comparison of population versus individual based cardiovascular disease
      prevention programs in Vasterbotten, Sweden.
AB  - The purpose of this paper is to determine if differences in health outcomes of
      two cardiovascular disease prevention programs can be attributed to the inclusion
      of population based efforts in one of the programs. Propensity score matching has
      been used to eliminate possible selection bias. The results indicate that the
      intervention including population-based measures was not more effective than the
      intervention directed toward the individual.

PMID- 16280185
TI  - Roles of acetylation and other post-translational modifications in melanocortin
      function and interactions with endorphins.
AB  - Phylogenetic, developmental, anatomic, and stimulus-specific variations in post
      translational processing of POMC are well established. For melanocortins, the
      role of alpha-N-acetylation and the selective activities of alpha, beta, and
      gamma forms are of special interest. Acetylation may shift the predominant
      activity of POMC products between endorphinergic and melanocortinergic actions
      which are often in opposition. This review addresses: (1) variations in POMC
      processing; (2) the influence of acetylation on the functional activity of alpha
      MSH; (3) state- and stimulus-dependent effects on the proportional distribution
      of forms of melanocortins and endorphins; (4) divergent effects of alpha-MSH and
      beta-endorphin administration; (5) potential roles of beta- and gamma-MSH.

PMID- 16280186
TI  - Effects of age on feeding behavior and chemosensory processing in the pond snail,
      Lymnaea stagnalis.
AB  - This study used behavioral and electrophysiological techniques to examine age
      related changes in the feeding behavior and chemosensory processing in the pond
      snail, Lymnaea stagnalis. Increasing age was associated with a 50% decrease in
      long-term food consumption. Analysis of short-term sucrose-evoked feeding bouts
      showed an age-related increase in the number of animals that failed to respond to
      the stimulus. Of the animals that did respond increasing age was associated with
      a decrease in the number of sucrose-evoked bites and a increase in the duration
      of the swallow phase. These changes were observed with both 0.01 and 0.05M
      sucrose stimuli but were not seen when 0.1M sucrose was used as the stimulus.
      Electrophysiological analysis of the chemosensory pathway in semi-intact lip-CNS
      preparations failed to demonstrate a significant change in the neuronal
      information entering the cerebral ganglia from the lips via the median lip nerve,
      but did demonstrate an age-related deficit in the neuronal output from the
      cerebral ganglia. This deficit was also dependent on the sucrose concentration
      and mirrored the concentration-dependent changes in feeding behavior. In summary,
      aging appeared to affect central but not peripheral processing of chemosensory
      information and suggests that this deficit contributes to the age-related changes
      in feeding behavior.

PMID- 16280187
TI  - Urinary cortisol excretion as a predictor of incident cognitive impairment.
AB  - Elevated glucocorticoid levels have been associated with cognitive impairment,
      including dementia. However, few longitudinal studies have examined the
      association between resting cortisol levels and the incidence of cognitive
      impairment. We measured overnight urinary excretion of cortisol in 538 high
      functioning men and women, 70-79 years of age, in 1988, and assessed their
      cognitive functioning in 1988, 1991, and 1995 using the short portable mental
      status questionnaire (SPMSQ). Compared to participants in the bottom quartile of
      urinary cortisol at baseline, those in the top three quartiles had higher risk of
      incident cognitive impairment over the 7-year follow up (i.e., decline in SPMSQ
      score to below six out of nine). This association was not affected by adjustment
      for age, gender, education level, ethnicity, smoking, prevalent cardiovascular
      disease, and blood pressure (adjusted odds ratio for the highest quartile 2.34,
      95% confidence interval, 1.07-5.14). There was no effect modification by gender;
      the association was equally strong in men and women. We conclude that urinary
      excretion of cortisol predicts incident cognitive impairment in older men and
      women.

PMID- 16280188
TI  - How far can the antigen content of tissue culture rabies vaccine be reduced
      safely?

PMID- 16280189
TI  - Imposex occurrence in marine whelks at a military facility in the high Arctic.
AB  - Imposex was found in the Arctic whelk Buccinum finmarkianum at several marine
      stations off Thule Air Base, an US military facility in Northwest Greenland. This
      indicates a widespread contamination with the antifouling agents, tributyltin
      (TBT) or triphenyltin (TPhT) in the area, but such contamination was not
      supported by the organotin analyses in sediments, whelks and clams, which in
      general was below the analytical detection limit. Organotin concentrations above
      the detection limit were found only at one station close to a quay, where the
      highest frequency of imposex also occurred. This suggests that imposex in B.
      finmarkianum is a biomarker of TBT more sensitive than the detection limits,
      which the analytical chemistry could achieve in this study.

PMID- 16280190
TI  - Lead shot from hunting as a source of lead in human blood.
AB  - This study investigates the relationship between the intake of birds hunted with
      lead shot and the lead concentration in human blood. Fifty adult men from Nuuk,
      Greenland took part in the study. From September 2003 to June 2004 they regularly
      gave blood samples and recorded how many birds they ate. We found a clear
      relationship between the number of bird meals and blood lead and also a clear
      seasonal variation. The concentration was highest in mid-winter when bird
      consumption is at its highest. Blood lead was low (15 microg/L, mean
      concentration) among the participants reporting not eating birds. Among those
      reporting to eat birds regularly, blood lead was significantly higher, up to 128
      microg/L (mean concentration). Concentrations depended on the frequency of bird
      meals: the more the bird meals, the higher the resulting blood lead. This clear
      relationship points to lead shot as the dominating lead source to people in
      Greenland.

PMID- 16280191
TI  - A meta-analysis of parent training: moderators and follow-up effects.
AB  - A meta-analysis of 63 peer-reviewed studies evaluated the ability of parent
      training programs to modify disruptive child behaviors and parental behavior and
      perceptions. This analysis extends previous work by directly comparing behavioral
      and nonbehavioral programs, evaluating follow-up effects, isolating dependent
      variables expressly targeted by parent training, and examining moderators.
      Effects immediately following treatment for behavioral and nonbehavioral programs
      were small to moderate. For nonbehavioral programs, insufficient studies
      precluded examining follow-up effects. For behavioral programs, follow-up effects
      were small in magnitude. Parent training was least effective for economically
      disadvantaged families; importantly, such families benefited significantly more
      from individually delivered parent training compared to group delivery. Including
      children in their own therapy, separate from parent training, did not enhance
      outcomes.

PMID- 16280192
TI  - Sickness absence and sickness attendance--what people with neck or back pain
      think.
AB  - This study explores the decision of 33 men and women to be sick-listed from work
      for neck pain or low-back pain. Qualitative interviews with the subjects, who
      lived in a city or a sparsely populated area of Sweden, were tape-recorded,
      transcribed and analysed in the interpretive tradition by the three authors. New,
      intense and threatening pain quickly made persons report sick. For other pain,
      sickness absence, its timing and duration, were negotiated on the basis of the
      subjects' self-image, work-duty norms, organisational and extra-organisational
      work factors. Thirty-one people aimed to return to work, but spine-related pain
      was a hindrance. Five strategies to avoid, delay or shorten sickness absence were
      identified. Concepts of the illness flexibility model well described how the
      workers balanced the factors driving them from work and those forcing them or
      attracting them to remain. The conclusion is that reporting sick is neither
      undertaken lightly nor for short-term reasons only. Instead, personal history and
      anticipated future, spine-related pain, workplace and labour market factors are
      also important considerations.

PMID- 16280193
TI  - Macrocephaly and the control of brain growth in autistic disorders.
AB  - Autism is a childhood-onset neuropsychiatric disorder characterized by marked
      impairments in social interactions and communication, with restricted stereotypic
      and repetitive patterns of behavior, interests, and activities. Genetic
      epidemiology studies indicate that a strong genetic component exists to this
      disease, but these same studies also implicate significant environmental
      influence. The disorder also displays symptomatologic heterogeneity, with broad
      individual differences and severity on a graded continuum. In the search for
      phenotypes to resolve heterogeneity and better grasp autism's underlying biology,
      investigators have noted a statistical overrepresentation of macrocephaly, an
      indicator of enlarged brain volume. This feature is one of the most widely
      replicated biological findings in autism. What then does brain enlargement
      signify? One hypothesis invoked for the origin of macrocephaly is a reduction in
      neuronal pruning and consolidation of synapses during development resulting in an
      overabundance of neurites. An increase in generation of cells is an additional
      mechanism for macrocephaly, though it is less frequently discussed in the
      literature. Here, we review neurodevelopmental mechanisms regulating brain growth
      and highlight one underconsidered potential causal mechanism for autism and
      macrocephaly--an increase in neurogenesis and/or gliogenesis. We review factors
      known to control these processes with an emphasis on nuclear receptor activation
      as one signaling control that may be abnormal and contribute to increased brain
      volume in autistic disorders.

PMID- 16280194
TI  - Spontaneous patterned retinal activity and the refinement of retinal projections.
AB  - A characteristic feature of sensory circuits is the existence of orderly
      connections that represent maps of sensory space. A major research focus in
      developmental neurobiology is to elucidate the relative contributions of neural
      activity and guidance molecules in sensory map formation. Two model systems for
      addressing map formation are the retinotopic map formed by retinal projections to
      the superior colliculus (SC) (or its non-mammalian homolog, the optic tectum
      (OT)), and the eye-specific map formed by retinal projections to the lateral
      geniculate nucleus of the thalamus. In mammals, a substantial portion of
      retinotopic and eye-specific refinement of retinal axons occurs before vision is
      possible, but at a time when there is a robust, patterned spontaneous retinal
      activity called retinal waves. Though complete blockade of retinal activity
      disrupts normal map refinement, attempts at more refined perturbations, such as
      pharmacological and genetic manipulations that alter features of retinal waves
      critical for map refinement, remain controversial. Here we review: (1) the
      mechanisms that underlie the generation of retinal waves; (2) recent experiments
      that have investigated a role for guidance molecules and retinal activity in map
      refinement; and (3) experiments that have implicated various signaling cascades,
      both in retinal ganglion cells (RGCs) and their post-synaptic targets, in map
      refinement. It is likely that an understanding of retinal activity, guidance
      molecules, downstream signaling cascades, and the interactions between these
      biological systems will be critical to elucidating the mechanisms of sensory map
      formation.

PMID- 16280195
TI  - Relationships between vocal characteristics and body size and shape in human
      males: an evolutionary explanation for a deep male voice.
AB  - A deep male voice may play a role in courtship and competitive behaviours in
      humans by attracting female mates and indicating body size to male competitors.
      The current correlational study investigated the relationship between vocal
      measures (fundamental and formant frequencies) and both body size and shape.
      Vocal samples and physical measures were obtained from 50 heterosexual male
      volunteers. A significant negative relationship was found between fundamental
      frequency and measures of body shape and weight. Further, a significant negative
      relationship was found between formant dispersion (the relationship between
      successive formant frequencies) and measures of body size as well as body shape.
      Findings are discussed in relation to the 'good genes' model of sexual selection
      and the size exaggeration theory of laryngeal descent.

PMID- 16280196
TI  - Biochemical diagnosis of organophosphate-insensitivity with neural
      acetylcholinesterase extracted by sonication from the adult tick synganglion.
AB  - A sonication method for the homogeneous extraction of acetylcholinesterase (AChE)
      from the synganglia of adult ticks is described. The method provides for the
      extraction of sufficient AChE for multiple assays of enzyme activity in the
      presence of specific organophosphate (OP) inhibitors for the rapid diagnosis of
      OP-insensitivity and assignment of homozygous susceptible (SS), heterozygous
      resistant (RS), and homozygous resistant (RR) genotypes to individual ticks. A
      single synganglion from adult ticks of either gender and various stages of
      feeding can successfully be used for AChE extraction. The study presents the
      results of diagnostic screening of four Boophilus microplus strains for OP
      insensitivity. The extraction method and these findings should find utility in
      support of researchers involved in the mitigation of acaricide resistance in tick
      populations worldwide, and in particular, the Cattle Fever Tick Surveillance and
      Quarantine Program maintained by USDA-APHIS/Veterinary Services along the south
      Texas border that prevents reentry of Boophilus spp. into the United States from
      endemic populations in Mexico.

PMID- 16280197
TI  - Generally applicable methods to purify intracellular coccidia from cell cultures
      and to quantify purification efficacy using quantitative PCR.
AB  - The objective of this study was to evaluate the utility of a simple, efficient,
      and rapid method for the isolation of Sarcocystis neurona merozoites and
      Besnoitia darlingi tachyzoites from cultured cells. The efficacy of this
      purification method was assessed by microscopy, SDS-PAGE, Western blotting,
      immuno-fluorescence, and three novel quantitative PCR assays. Culture medium
      containing host cell debris and parasites was eluted through PD-10 desalting
      columns. This purification method was compared to alternatives employing
      filtration through a cellulose filter pad or filter paper. The estimated recovery
      of S. neurona merozoites purified by the column method was 82% (+/-3.7) of the
      original merozoites with 97.5% purity. In contrast, estimated recovery of S.
      neurona merozoites purified by filter pad and filter paper was 40% and 30% with
      76% and 83% purity, respectively. The same procedures were applied to purify B.
      darlingi tachyzoites from cultured cells. Of the original cultured B. darlingi
      tachyzoites, 94% (+/-2.5) were recovered from the PD-10 column with 96.5%, purity
      whereas percentage recovery of B. darlingi tachyzoites purified by filter pad and
      filter paper were 51% and 35% with 84% and 88% purity, respectively. All
      described methods maintained sterility so that purified parasites could be
      subsequently cultured in vitro. However, purification using a PD-10 column
      minimized parasite loss and the loss of viability as determined by the trypan
      blue dye exclusion assay, the rate of parasite production, and plaque forming
      efficiency in cell culture. Moreover, column-purified parasites improved the
      sensitivity of an immuno-fluorescent (IFA) analysis and real-time quantitative
      PCR assays targeted to parasite 18S ribosomal DNA and hsp70 genes. This technique
      appears generally applicable for purifying coccidia grown in cell cultures.

PMID- 16280198
TI  - Comparative plasma dispositions of ivermectin and doramectin following
      subcutaneous and oral administration in dogs.
AB  - This study evaluates the comparative plasma dispositions of ivermectin (IVM) and
      doramectin (DRM) following oral and subcutaneous administration (200 microg/kg)
      over a 40-day period in dogs. Twenty bitches were allocated by weight in to four
      groups (Groups I-IV) of five animals each. Animals in the first two groups
      (Groups I and II) received orally the injectable solutions of IVM and DRM,
      respectively, at the dose of 200 microg/kg bodyweight. The other two groups
      (Groups III and IV) received subcutaneously injectable solutions at the same dose
      rate. Blood samples were collected between 1h and 40 days after treatment and the
      plasma samples were analysed by high performance liquid chromatography (HPLC)
      using fluorescence detection. The results indicated that IVM produced a
      significantly higher maximum plasma concentration (C(max): 116.80+/-10.79 ng/ml)
      with slower absorption (t(max): 0.23+/-0.09 day) and larger area under the
      concentration versus time curve (AUC: 236.79+/-41.45 ng day/ml) as compared with
      DRM (C(max): 86.47+/-19.80 ng/ml, t(max): 0.12+/-0.05 day, AUC: 183.48+/-13.17 ng
      day/ml) following oral administration of both drugs; whereas no significant
      differences were observed on the pharmacokinetic parameters between IVM and DRM
      after subcutaneous administrations. In addition, subcutaneously given IVM and DRM
      presented a significantly lower maximum plasma concentration (C(max): 66.80+/
      9.67 ng/ml and 54.78+/-11.99 ng/ml, respectively) with slower absorption (t(max):
      1.40+/-1.00 day and 1.70+/-0.76 day, respectively) and larger area under the
      concentration versus time curve (AUC: 349.18+/-47.79 ng day/ml and 292.10+/-78.76
      ng day/ml, respectively) as compared with the oral administration of IVM and DRM,
      respectively. No difference was observed for the terminal half-lives
      ((t(1/2lambda(z)) and mean residence times (MRT) of both molecules. Considering
      the pharmacokinetic parameters, IVM and DRM could be used by the oral or
      subcutaneous route for the control of parasitic infection in dogs.

PMID- 16280199
TI  - Seroprevalence of Toxoplasma gondii antibodies in captive mithuns (Bos frontalis)
      from India.
AB  - One hundred and four mithuns from India were tested for serum antibodies to
      Toxoplasma gondii by modified direct agglutination test. The overall prevalence
      of T. gondii antibodies in mithun was 28% (95% CI=19-37). Highest (prevalence
      rate=46, 95% CI=30-62) seroprevalence of T. gondii antibodies was found in
      mithuns above 3 years of age and lowest (prevalence rate=14, 95% CI=1-27) in
      mithuns of 6 months-1 year old. No statistically significant difference was
      observed between male (prevalence rate=23, 95% CI=10-36) and female (prevalence
      rate=31, 95% CI=20-42) seroprevalences (P=0.53). Significant difference was
      observed in the seroprevalence of T. gondii antibodies in mithuns of different
      strains with the highest (48%) seroprevalence recorded in Arunachal and lowest
      (14%) in Mizoram strain. The seroprevalence was higher in farm located at lower
      altitude (305 m a.s.l.) than the farm located at higher altitude (2134 m a.s.l.).
      This is the first serologic survey for T. gondii antibodies performed on mithuns
      from India.

PMID- 16280200
TI  - Characterization of a methionine adenosyltransferase over-expressing strain in
      the trypanosomatid Leishmania donovani.
AB  - Methionine adenosyltransferase (MAT: EC 2.5.1.6) catalyzes the synthesis of S
      adenosylmethionine (AdoMet) in two sequential steps, AdoMet formation and
      subsequent tripolyphosphate (PPPi) cleavage, induced by AdoMet. In pursuit of a
      better understanding of the biological function of the enzyme, the MAT gene was
      cloned into vector PX63NEO to induce episomal overexpression in leishmania
      parasites. Neomycin-selected clones originated a strain of such overexpressing
      parasites that accumulated more than 3-fold AdoMet than mock-transfected cells
      and showed over ten times the wild type MAT activity, concurring with a
      significant accumulation of the MAT protein during the early logarithmic phase
      and MAT transcripts throughout the growth cycle. The rate of AdoMet efflux,
      practically nil in the control promastigotes, was exceptionally high in the MAT
      overexpressing parasites, whilst growth in this strain was comparable to
      development in control cells, i.e., it was not affected by deleterious
      hypermethylation. Moreover, the modified strain was 10-fold more resistant to
      sinefungin, a S-adenosylmethionine-like antibiotic, than control cells. The
      effects of overexpression on polyamine metabolism and transport were likewise
      studied.

PMID- 16280201
TI  - Temporal changes in cellular energy following burn injury.
AB  - Availability of ADP is a predominant influence on respiratory control. Associated
      with severe burn injury is an increase in energy expenditure. The purpose of this
      study was to determine the temporal changes in ATP, ADP, NAD, and NADH following
      severe burn and thereby assess any related alterations in respiratory control and
      energy deficit. During isoflurane anesthesia and following intraperitoneal
      injection of saline, 32 mice were flame burned at 40% body surface area. Twelve
      mice served as controls. At 12, 24, 72, and 168 h post-burn, groups of mice
      underwent celiotomy with determination of hepatic surface blood flow using laser
      Doppler and oxygen saturation using pulse oximetry. Biopsies of liver were then
      frozen in liquid nitrogen for subsequent quantification of ATP, ADP, AMP, NAD,
      and NADH by HPLC. Mortality was 12.5% at 72 h post-burn and 25% at 1 week. Oxygen
      saturation and hepatic surface blood flow remained similar to control values
      throughout the week after burn. ATP, ADP, and energy charge decreased
      progressively following burn reaching a significant decrease from unburned
      controls at 72 h. Availability of NADH remained statistically similar to unburned
      controls throughout the week after burn. These results demonstrate that despite
      maintenance of baseline oxygen delivery, there was a nadir in ATP and ADP
      availability and energy charge in the liver at 72 h after burn. This finding
      supports the concept of a limitation in phosphorylation after injury.
      Availability of NADH remained at or above pre-burn concentrations suggesting that
      the rate of fuel oxidation was not a limiting factor for ongoing oxidative
      phosphorylation for energy.

PMID- 16280202
TI  - Update on ovine footrot in New Zealand: isolation, identification, and
      characterization of Dichelobacter nodosus strains [corrected].
AB  - Dichelobacter nodosus, a Gram-negative strict anaerobe, is the essential
      causative agent of ovine footrot. Despite its worldwide presence, the disease has
      significant economic impact in those sheep-farming countries with a temperate
      climate and moderate to high rainfall, such as New Zealand (NZ) and Australia. In
      this study, we aimed to isolate, identify, and characterize as many D. nodosus
      strains as possible from NZ farms by using polymerase chain reaction (PCR)-based
      technology. Understanding the virulence of this bacterium and showing extensive
      genomic variation in the fimbrial subunit gene (fimA) in different D. nodosus
      strains was very important to produce serogroup specific and effective vaccine
      for NZ. More than 100 footrot samples were collected from four different farming
      regions in NZ. Thousands of primary plates were cultured anaerobically and
      examined with Gram-staining in order to detect single colonies of D. nodosus.
      Approximately 500 plates that had potential D. nodosus colonies were subcultured
      several times to eliminate contaminating colonies until single colonies were
      obtained. Variable and a part of the conserved regions of the fimbrial subunit
      gene (fimA) were amplified directly from bacterial DNA extracted from footrot
      lesions and also from cultured NZ D. nodosus isolates, using the polymerase chain
      reaction. Different fimA amplimers were analyzed by DNA sequencing. On the basis
      of DNA sequence analysis, 16 new D. nodosus isolates belonging to eight different
      serogroups were identified from NZ. These new D. nodosus fimA sequences from NZ
      were different to previously reported strains and strains used in a commercial
      vaccine.

PMID- 16280203
TI  - Identification of three novel mycoplasma species from ostriches in South Africa.
AB  - Mycoplasmas have been implicated in certain clinical syndromes in ostriches and
      are associated with upper respiratory tract infections. As these infections
      result in production losses, they are of considerable economic importance to the
      South African ostrich industry. Although poultry mycoplasmas have been shown to
      infect ostriches, the existence of unique ostrich-specific mycoplasmas has been
      suggested. In this study, mycoplasmas were isolated from ostriches in the Klein
      Karoo, Central Karoo and Garden Route areas of the Western and Northern Cape
      Provinces of South Africa and identified using 16S rRNA gene sequencing. These
      sequences indicated that ostriches in these areas carry three unique mycoplasmas
      and were not infected with chicken mycoplasmas. Phylogenetic analysis of the 16S
      rRNA sequences of the three isolated ostrich mycoplasmas showed them to be quite
      divergent and to fall into two distinct phylogenetic groupings. Unique sequences
      within the 16S rRNA gene of the ostrich mycoplasmas were subsequently used for
      the development of specific primers for the detection and diagnosis of mycoplasma
      infections in ostriches. Chickens kept in close proximity to infected ostriches
      were not infected with these ostrich mycoplasmas.

PMID- 16280204
TI  - Molecular markers for detection of pathogenic Escherichia coli strains belonging
      to serogroups O 138 and O 139.
AB  - Escherichia coli strains belonging to O-serogroup 138 and 139 are important as
      disease agents in pigs causing post-weaning diarrhea and edema disease. Several
      types of shiga toxin-producing O 138 and O 139 strains were isolated from
      diarrheic humans and from cattle and food of bovine origin. Serotyping is the
      current method for detection of O 138 and O 139 strains but its applicability can
      be limited due to the presence of capsules and capsular-like bacterial surface
      antigens and in the case of rough LPS. To overcome these difficulties for
      diagnosis, we have developed a specific PCR method suitable for detection of
      different types of O 138 and O 139 strains. The O-antigen gene clusters of E.
      coli O 138 and O 139 type strains were sequenced, and the genes were identified
      on the basis of homology. By screening against 186 E. coli and Shigella type
      strains, two genes specific to each of E. coli O 138 and O 139 were identified,
      respectively, and were tested on 15 clinical and environmental isolates of those
      two serogroups in a double-blind test. The sensitivity of the PCR assays was
      determined, and the detection limits were 2 pg per mul of chromosomal DNA and 2
      CFU per 10 g of water or pork samples. PCR-based detection of O-antigen specific
      genes of E. coli O 138 and O 139 was shown to be accurate, highly sensitive and
      rapid, and is suggested as a new diagnostic tool for investigations of infections
      and outbreaks with these strains in animals and humans and for control of food.

PMID- 16280205
TI  - Sow performance in an endemically porcine reproductive and respiratory syndrome
      (PRRS)-infected farm after sow vaccination with an attenuated PRRS vaccine.
AB  - The objective of this field study was to evaluate in an endemically porcine
      reproductive and respiratory syndrome (PRRS) virus-infected farm the reproductive
      performance of sows after their vaccination with a PRRS attenuated vaccine. In a
      farrow-to-finish pig farm with history of endemic PRRS virus infection, a total
      of 200 gilts and sows were used. They were divided in 2 groups of 100 animals.
      The first group was used as untreated controls, while the animals of the second
      group were vaccinated against PRRS virus using the attenuated Porcilis PRRS
      vaccine (Intervet International, The Netherlands) based on European strain. All
      health and reproductive parameters were recorded from the time of vaccination up
      to next weaning. No adverse systemic or local reactions or side effects relative
      to vaccination were noted. Compared to controls, vaccinated sows showed
      significantly improved farrowing rate (89% versus 78%) and a tendency for fewer
      returns to oestrus, particularly those at irregular intervals. Fewer sows
      farrowed prematurely and showed post-partum dysgalactia syndrome, but more live
      pigs were born and weaned in each litter after vaccination. It was concluded that
      vaccination of sows with Porcilis PRRS attenuated vaccine in farms with endemic
      PRRSV infection has beneficial effects on their health and fertility.

PMID- 16280207
TI  - Serogrouping of United States and some African serotypes of bluetongue virus
      using RT-PCR.
AB  - The diagnostic potential of RT-PCR for detection of bluetongue virus (BTV)
      ribonucleic acid (RNA) sequence in cell culture and tissue samples from infected
      ruminants from United States, Sudan, South Africa and Senegal, was evaluated. The
      non structural protein 1 (NS1) gene of North American BTV serotype 11 was
      targeted for PCR amplification. The United States BTV serotypes 2, 10, 11, 13 and
      17 and the Sudanese BTV serotypes 1, 2, 4 and 16 and BTV serotype 4 from South
      Africa and BTV serotype 2 from Senegal were studied. RNAs from all BTV field
      isolates used in this study, propagated in cell cultures, were detected by the
      described RT-PCR-based assay. The first specific 790bp BTV PCR products were
      amplified using a pair of outer primers (BTV1 and BTV2). Specificity of the PCR
      products was confirmed by a nested amplification of a 520bp PCR product using a
      pair of internal (nested) primers (BTV3 and BTV4). The BTV PCR products were
      visualized on ethidium bromide-stained agarose gels. Amplification products were
      not detected when the RT-PCR-based assay was applied to RNAs from closely related
      orbiviruses including, epizootic hemorrhagic disease virus (EHDV) prototypes
      serotypes 1, 2, 4; RNA from Sudanese isolate of palyam orbiviruses serogroup and
      total nucleic acid extracts from uninfected Vero cells. Application of the nested
      BTV RT-PCR to clinical samples resulted in amplification of BTV RNA from blood
      and serum samples from goats experimentally infected with BTV4 and from naturally
      infected sheep, goats, cattle and deer. The results of this study indicated that
      this RT-PCR assay could be applied for rapid detection of BTV, in cell culture
      and clinical samples from susceptible ruminants during an outbreak of the
      disease, in the United States and African.

PMID- 16280206
TI  - The occurrence of treponemes in contagious ovine digital dermatitis and the
      characterisation of associated Dichelobacter nodosus.
AB  - Contagious ovine digital dermatitis (CODD) is a recently recorded, apparently new
      infection of the ovine hoof, which differs clinically from footrot caused by
      Dichelobacter nodosus and which fails to respond well to accepted treatment
      practices for footrot. Despite the welfare implications of such an infection,
      very little research has been performed on CODD to date and the aetiology remains
      confused. Suggestions have been made that there is a potential role for
      treponemes in the pathogenesis of CODD but that D. nodosus is apparently not
      involved. Six farms were therefore targeted in this study to provide a more in
      depth investigation into the bacterial flora of CODD lesions. Dark ground
      microscopy, culture and PCR techniques were used, concentrating on the presence
      of D. nodosus and spirochaetes, particularly those of the genus Treponema. The
      results demonstrated that isolates of D. nodosus were indeed present in a high
      percentage (74%) of CODD lesions compared with 31% of apparently healthy feet.
      The isolates were shown to be of similar virulence type to those reported
      previously in cases of footrot, and the range of serogroups was also found to be
      similar to footrot, with serogroup H being prevalent. Treponemes were present in
      70% of CODD lesions and 38% of apparently healthy feet, supporting a possible
      association between CODD and treponemes. However, any further progress on the
      aetiology of CODD and the potential for novel, effective treatment will depend on
      an improved ability to culture these organisms routinely in the laboratory
      thereby enabling their complete characterisation.

PMID- 16280208
TI  - Arterial and venous Doppler in the diagnosis and management of early onset fetal
      growth restriction.
AB  - Key issues in the management of early onset fetal growth restriction (IUGR<34
      weeks) are accurate diagnosis and assessment of fetal well-being to optimize
      timing of delivery by weighing fetal vs. neonatal risks. Cardiovascular,
      behavioral and fetal heart rate patterns in IUGR follow a predictable progression
      that corresponds with the severity of compromise. Umbilical artery (UA) Doppler
      primarily serves as a placental function test providing insufficient information
      to solely direct perinatal management. Venosus Doppler is an independent
      predictor of stillbirth and acidemia and needs to be examined when the UA index
      is elevated, especially if end-diastolic velocities are absent. Neonatal outcomes
      are primarily determined by gestational age and their antenatal prediction is too
      ineffective to guide management. Abnormal venous Doppler, biophysical profile
      score and mean minute variation of the fetal heart rate are strong predictors of
      fetal compromise therefore favoring delivery. Randomized trials indicate that
      delayed delivery has little effects on short-term outcome while producing a trend
      towards improved early childhood neurodevelopment. This stresses the need for
      excellent fetal surveillance techniques and their ongoing investigation through
      randomized management trials.

PMID- 16280209
TI  - Biological monitoring of welders exposed to aluminium.
AB  - To evaluate an adequate strategy for biological monitoring of aluminium (Al), a
      group of 62 Al welders (age in 1999: 23-51 years, median 35 years) was surveyed
      annually from 1999 to 2003 by determination of pre- and post-shift Al in urine
      and plasma. Biomonitoring was supplemented by personal air measurements of the
      total dust concentration. The welders' internal exposure was compared to the
      exposure of 60 non-exposed assembly workers (age in 1999: 21-51 years, median: 36
      years) who were surveyed in 1999, 2001 and 2003. Having a nearly constant dust
      exposure, median concentrations of Al in urine (Al in plasma) of the welders
      decreased from 40.1 microg/g to 19.8 microg/g creatinine (8.7 to 4.6 microg/l).
      For the control group the median levels of Al in urine (plasma) ranged from 4.8
      microg/g to 5.2 microg/g creatinine (2.4-4.3 microg/l) indicating a higher
      sensitivity for the marker Al in urine. No systematic differences have been found
      between pre- and post-shift internal exposure. This might be caused by the slow
      elimination kinetics and low systemic bioavailability of Al. A correlation
      analysis did not yield close relationships between dust exposure, Al in plasma
      and Al in urine underlining the importance of biomonitoring for assessment of Al
      exposure.

PMID- 16280210
TI  - Suppressive effect of 1-nitropyrene on benzo[a]pyrene-induced CYP1A1 protein
      expression in HepG2 cells.
AB  - The genotoxicity of polycyclic aromatic hydrocarbons (PAHs) and nitrated PAHs may
      be influenced by the interaction of the compounds. In this study, our data showed
      that benzo[a]pyrene (BaP)-DNA adduct levels were decreased in a dose-dependent
      manner when the human hepatoma cell line HepG2 simultaneously treated with BaP
      and 1-nitropyrene (1-NP). To further investigate the molecular mechanism by which
      1-NP interferes with the covalent binding of BaP to DNA, we conducted experiments
      to analyze the mRNA level and protein stability of cytochrome P450 1A1 (CYP1A1),
      which is engaged in the activation of BaP, leading to the generation of BaP-DNA
      adducts. Northern blot analysis presented that 1-NP attenuated BaP-induced CYP1A1
      mRNA expression by 30.4-39.6% (p < 0.05). Western blot analysis revealed that the
      co-treatment with BaP and 1-NP resulted in a significant inhibition of BaP
      induced CYP1A1 protein expression (70.7-88.2%, p < 0.05). However, the decrease
      in CYP1A1 protein levels was significantly larger than that in CYP1A1 mRNA
      levels. To confirm the effect of 1-NP on the CYP1A1 protein expression, in vitro
      proteolysis of CYP1A1 protein was evaluated. The results demonstrated that the
      addition of 1-NP enhanced CYP1A1 protein degradation and the proteolysis of
      CYP1A1 protein was inhibited by the addition of an antioxidant, dithiothreitol.
      In addition, the relative levels of reactive oxygen species (ROS) were elevated
      in HepG2 cells co-treated with BaP and 1-NP, indicating that the decrease of
      CYP1A1 protein level was probably attributed to the production of ROS generated
      by binary mixture. Taken together, these findings suggested that the
      transcriptional suppression and posttranslational mechanism may be involved in
      loss of CYP1A1 protein, causing the decrease of BaP-DNA adduct levels in the
      presence of binary mixtures of 1-NP and BaP.

PMID- 16280211
TI  - Expression profiling of estrogen-responsive genes in breast cancer cells treated
      with alkylphenols, chlorinated phenols, parabens, or bis- and benzoylphenols for
      evaluation of estrogenic activity.
AB  - We examined expression profiles of estrogen-responsive genes after treatment with
      alkylphenols (p-cresol (pC), 4-n-ethylphenol (4EP), 4-n-heptylphenol (4HP), 4-t
      octylphenol (4OP) and nonylphenol (NP)), chlorinated phenols (4-chlorophenol
      (4CP), 4-chloro-3,5-dimethylphenol (CDP), 2,4-dichlorophenol (DCP) and
      pentachlorophenol (PCP)), parabens (methylparaben (MPB), ethylparaben (EPB)
      propylparaben (PPB) and butylparaben (BuPB)), or bis- and benzoylphenols
      (bisphenols A and B and p-hydroxybenzophenone (pHBP)) by means of a DNA
      microarray assay first to evaluate the estrogenic activity of these chemicals and
      then to understand the structural basis for the activity. By selecting a set of
      120 genes showing greater statistical reliability for estrogen, a more reliable
      assay for each of the chemicals was achieved and, for the chemicals for which
      data were available, the results were consistent with those of previously
      reported estrogen receptor-binding and yeast two-hybrid assays except for
      chlorinated and few other phenols. Evaluation of the chemicals based on gene
      function indicated that the genes related to proliferation, transcription and
      transport were mostly up-regulated while significant numbers of genes related to
      enzymes and signaling were down-regulated. The genes related to transcription
      showed the highest degree of variation among the six functional categories
      (enzymes, signaling, proliferation, transcription, transport and others) for the
      chemicals with relatively high levels of estrogenic activity. These results
      indicate that the variations in chemicals and their biological effects can be
      monitored by the appropriate grouping of estrogen-responsive genes.

PMID- 16280212
TI  - Adduction of biomacromolecules with acrylamide (AA) in mice at environmental dose
      levels studied by accelerator mass spectrometry.
AB  - Since 2002, WHO has strongly called scientists to investigate intensively the
      toxicity and potential carcinogenicity of acrylamide (AA), because humans are
      widely exposed to AA via various foodstuffs. In this study we measured the
      biomacromolecule adducts of [2,3-(14)C]AA (0, 7.5 x 10(-2), 7.5 x 10(-1), 7.5,
      9.3 x 10(1), 2.4 x 10(2) and 1.0 x 10(3)microg/kg b.w.) in adult male mice by
      ultrasensitive accelerator mass spectrometry (AMS) technique. The aim is to
      evaluate the potential molecular toxicity of AA at human relevant dose levels,
      particularly towards the sperm cells. Hemoglobin (Hb), serum albumin (SA),
      protamine, sperm DNA, tails and heads were isolated 24h post dosing and the
      adduct levels were measured by AMS, respectively. Good log/log linear dose
      response correlations were established. Moreover, the correlation of AA-protamine
      adducts, AA-sperm DNA adducts, as well as AA-sperm head/tail adducts with AA-Hb
      or AA-SA adducts presented a linear log/log mode. In sperm, the formation of AA
      protamine adducts were predominating to AA-DNA adducts. The adducts on sperm
      heads/tails might both influence the fertility efficacy.

PMID- 16280213
TI  - Follow-up biomonitoring after accidental exposure to acrylonitrile:- implications
      for protein adducts as a dose monitor for short-term exposures.
AB  - The analysis of protein adducts is a valuable tool for the biomonitoring of
      humans exposed to alkylating compounds. In case of single or intermittent
      exposures, however, the significance and validity of adduct analysis is limited
      due to the typically small increase in adduct levels and a nonlinear adduct
      elimination kinetic. This issue was addressed in a follow-up observation of four
      workers accidentally exposed to acrylonitrile (ACN) in a train depot. N-2
      Cyanoethylvaline (CEV) in hemoglobin was analyzed in blood samples of the workers
      and of seven rescue team and hospital members, approximately, 25 days after the
      accident. Of the 11 potentially exposed persons, only the cleaning workers
      revealed adduct levels significantly above the general background. Further blood
      samples of the workers were analyzed after 85, 115 and 175 days, respectively. In
      these cases, the adduct concentrations declined to background levels associated
      with individual smoking habits. A linear regression analysis of the data points
      to a total elimination interval of 148 days, 2 weeks longer than the standard
      lifespan of erythrocytes and possibly due to a period of acrylonitrile
      circulation in the blood stream or release from unstable intermediates. The data
      allow a rough estimate of the initial protein adduct concentration and an
      evaluation of the internal dose on the basis of biological exposure equivalents.
      In conclusion, adduct analyses offer valuable information even in the case of
      short-term exposures.

PMID- 16280214
TI  - Urinary incontinence in European women seeking treatment--results from a large
      observational study.

PMID- 16280215
TI  - Effects of 17beta-estradiol on matrix metalloproteinase-1 synthesis by human
      dermal fibroblasts.
AB  - BACKGROUND: Hormone replacement therapy (HRT) has been used in treatment of
      various menopausal disorders. It has been well documented that HRT increases the
      amount of dermal collagen and skin thickness in vivo. However little is known
      about the effects of female sex hormones on dermal fibroblasts in vitro.
      OBJECTIVE: The aim of this study is to determine whether or not 17beta-estradiol
      affects mRNA expression and production of type I collagen, matrix
      metalloproteinases-1 (MMP-1), tissue inhibitor metalloproteinases-1 (TIMP-1) or
      transforming growth factor-beta1 (TGF-beta1) by human dermal fibroblasts.
      METHODS: Fibroblasts were cultured with and without 17beta-estradiol for 6h. We
      evaluated the changes of mRNA expressions and protein production of type I
      collagen, MMP-1, TIMP-1 and TGF-beta1. RESULTS: The mRNA expressions of collagen
      alpha1(I), MMP-1, TIMP-1, TGF-beta1 were not changed by 17beta-estradiol
      stimulations at a concentration of 10(-12) to 10(-8) M. However, 17beta-estradiol
      at concentrations of 10(-12) and 10(-10) M exhibited inhibitory effects on proMMP
      1, but not type I collagen or TIMP-1 synthesis. The synthesis of TGF-beta1 by
      fibroblasts stimulated with 10(-8) M of estradiol was significantly increased as
      compared with the control. However, the level of TGF-beta type II receptor
      phosphorylation was not elevated under the same conditions. CONCLUSION:
      Suppressed synthesis of MMP-1 at a low concentration of 17beta-estradiol may be
      partly involved in the dermal tissue remodeling to inhibit the degradative
      change.

PMID- 16280216
TI  - Distribution of liposomal breviscapine in brain following intravenous injection
      in rats.
AB  - AIM: To investigate distribution of breviscapine in brain after intravenous
      (i.v.) injection of liposomes. METHODS: Breviscapine liposomes were prepared by
      rotary evaporation-sonication method. Particle size, encapsulation efficiency and
      stability of liposomes were respectively examined. In vitro drug release was
      investigated in 0.9% sodium chloride at 37 degrees C. Rats were divided into two
      groups. Liposomes were given to one group and commercial injection (Injectio
      Breviscapine) was given to the other at a single dose of 28.1 mgkg(-1) i.v.,
      respectively. Scutellarin in rat brain at different sampling time was determined
      by RP-HPLC. The brain concentration-time curves of breviscapine liposomes and
      commercial injection were constructed and pharmacokinetic parameters were
      calculated and compared by statistic analysis. RESULTS: The average liposome
      diameter was 735+/-59 nm and encapsulation efficiency was 85.1+/-2.3%. The
      average accumulative release percentage of breviscapine liposomes in 0.9% sodium
      chloride was less than 30% within 24h. The mean concentration-time curves of
      breviscapine liposomes and commercial injection were both fitted to one
      compartment model. There are significant difference of parameter T(1/2) and AUC(0
      360) between liposome and commercial injection (p<0.05). T(1/2) of breviscapine
      liposomes and commercial injection were 23.13+/-7.71 and 6.27+/-1.84min,
      respectively. The brain AUC ratio of breviscapine liposomes to commercial
      injection was 443.4+/-92.3%. CONCLUSION: Compared with the commercial injection,
      liposomes delivered more drugs into the brain and have longer elimination time.

PMID- 16280217
TI  - Screening of plants used in Danish folk medicine to treat memory dysfunction for
      acetylcholinesterase inhibitory activity.
AB  - Aqueous and methanolic extracts of 11 plants, used in Danish folk medicine for
      improvement of memory and cognition, and 3 Corydalis species were tested for
      acetylcholinesterase inhibitory activity using the Ellman colorimetric method.
      Significant inhibitory activity in dose-dependent manner was observed for
      extracts of Corydalis cava, Corydalis intermedia, Corydalis solida ssp. laxa and
      Corydalis solida ssp. slivenensis. Extracts of Ruta graveolens, Lavandula
      angustifolia, Rosmarinus officinalis, Petroselinum crispum and Mentha spicata
      exhibited moderate inhibition of the enzyme, defined as more than 15% at 0.1
      mg/ml.

PMID- 16280218
TI  - An electrocution by metal kite line.
AB  - A case is reported in which death is caused due to electrocution by a copper wire
      that was used as string of the kite. Electric current flowed through the copper
      wire of cut down kite when it touched power line transmitting alternate current
      of 240 V at 50 Hz. The free end of copper wire had abraded against the victim's
      shoulder, neck and face, and finally entangled around the ear. A unique type of
      electrical injury is noticed due to contact with live copper wire. This paper
      stresses the unique danger of the kite flying.

PMID- 16280220
TI  - Study of the diagnostic value of iron in fresh water drowning.
AB  - The aim of our study was to test the diagnostic value of iron (Fe) in fresh water
      drowning by investigating the postmortem levels of hemodilution in drowning cases
      compared to control cases. Twenty-six typical fresh water drowning cases were
      selected from 128 immersion cases autopsied in our Department of Forensic
      Pathology between 1998 and 2004. The exclusion criteria were a long postmortem
      interval and other causes of death than drowning. For all selected cases, the
      diagnosis of drowning was based on the presence of autopsy findings and positive
      diatom test. A control population of 12 cases was also selected. For each
      drowning and control case, iron blood levels were measured in the left ventricle
      (LV) and right ventricle (RV) of the heart. The mean difference of iron
      concentration (RVFe-LVFe) between the drowning group and the control group was
      statistically compared. Furthermore, iron measurements were performed in 19
      drowning cases showing advanced putrefaction. The mean difference of iron
      concentration was significantly higher in the drowning cases compared with
      controls (P<0.001). All drowning cases showed hemodilution. No overlap was found
      in the RVFe-LVFe levels between the two groups. Resuscitation attempts seemed to
      have no effect on the results. In cases of drowning showing advanced
      putrefaction, the iron test was not reliable because biochemical iron measurement
      was often prevented by no sufficient blood in the heart or postmortem clots. In
      conclusion, according to our results, iron seems to be a good biochemical marker
      in fresh water drowning with a short postmortem interval.

PMID- 16280219
TI  - Validation of nine non-CODIS STR loci for forensic use in a population from
      Central Poland.
AB  - The D7S1517, D3S1744, D12S391, D2S1360, D6S474, D8S1132, D5S2500, D10S2325 and
      D4S236613 are STR loci potentially useful for forensic purposes whose analysis
      has recently become facilitated by availability of a commercial kit. The purpose
      of the study was to evaluate the usefulness of these loci for forensic
      identification in a population of Central Poland. The distribution of alleles of
      the nine STRs was determined in sample of 353 unrelated individuals born in
      Central Poland and indices of forensic informativeness were calculated. The
      studied loci were highly informative and did not show departures from Hardy
      Weinberg equilibrium. For the loci located on the same chromosomes (D2S1360,
      D3S1744 D4S2366, D5S2500, D7S1517, D8S1132, D12S391) as other loci commonly used
      for identification purposes (TPOX, D2S1338, D3S1358, FGA, D5S818, D7S820, D8S1179
      and D12S391) appropriate pairwise analysis of linkage disequilibrium was
      performed. In all cases no statistically significant deviation from independence
      was found. We conclude that the studied STRs are informative and, when necessary,
      can be used to extend the results obtained with other STRs commonly analyzed for
      identification purposes, in particular the CODIS set.

PMID- 16280221
TI  - Patterns of genetic polymorphism at the 10 X-chromosome STR loci in Mongol
      population.
AB  - Genetic diversity at 10 X-chromosome STR loci has been approved and widely used
      for forensic science field. In this paper, we have studied this genetic diversity
      in various Mongol ethnic group with geographic backgrounds. Allele frequencies of
      10 X-chromosome STR loci, including DXS7133, DXS6799, DXS8378, DXS7423, DXS6804,
      HPRTB, DXS7424, DXS7132, DXS6789 and DXS101, were obtained from healthy unrelated
      individuals (53 females and 47 males) of Mongol ethnic group lived in north
      China. Gene diversity analysis showed that the average heterozygosity was
      uniformly high (0.687) in the studied population. The coefficient of PIC was
      0.99998.

PMID- 16280222
TI  - X-chromosome STRs analysis of Ewenke ethnic population.
AB  - X-chromosome STR, known as microsatellite, is a kind of the most information
      genetic markers for specific biological materials. Because the size of X
      chromosome STR alleles is small, generally including 100-350 nucleotides, it is
      relatively easy to be amplified and detected with high sensitivity. We have
      investigated 10 X-chromosome STR loci in an Ewenke ethnic population who live in
      Neimengu of northeast China. Allele frequencies of 10 X-chromosome STR loci,
      including DXS7133, DXS6799, DXS8378, DXS7423, DXS6804, HPRTB, DXS7424, DXS7132,
      DXS6789 and DXS101, were obtained from healthy unrelated individuals (45 females
      and 53 males) of Ewenke ethnic group.

PMID- 16280223
TI  - Raw material enzymatic activity determination: a specific case for validation and
      comparison of analytical methods--the example of superoxide dismutase (SOD).
AB  - Implementation of ICH guideline for validation of analytical methods was tested
      in the case of two enzymatic assays of determination of superoxide dismutase
      (SOD) activity. Analytical figures of merits of two tested methods (NBT reference
      method and the so called WST-1 method) demonstrate the feasibility of such
      approach. Nevertheless specification usually admitted for physicochemical method
      (e.g., HPLC), needs to be clearly enlarged, for instance, up to 10% for
      repeatability and 20% for reproducibility. On the other hand, the cross
      validation performed between the two enzymatic activity determination techniques,
      though based on the same principle, clearly shows that the quality of results
      depends on small variation in the experimental conditions. This shows that an
      enzymatic activity determination should be strictly related to the technique
      used, especially in the pharmaceutical control quality field, and confirms that
      analytical figures of merits are strongly function of the technique used.
      Finally, it was demonstrated that both NBT reference method and WST-1 method give
      strictly similar results.

PMID- 16280224
TI  - Composition analysis of two batches of polysorbate 60 using MS and NMR
      techniques.
AB  - Batch variation in Tween 60 has shown to influence the rheological properties of
      semisolid emulsions. MS (LC-MS, GC-MS, MS(n)) and NMR ((13)C, (1)H, (1)H COSY and
      HMBC) techniques were used to analyze and compare the composition of two batches
      of Tween 60 with particular emphasis on the number of POE groups and their
      distribution within the molecule. Acid and saponification values were also
      determined. The batches contained different proportions of components (sorbitan
      polyethoxylates, sorbitan monoester-diester-polyethoxylates and isosorbide
      monoester-diester-polyethoxylates). The number of POE groups were averaged over
      the four sites in sorbitan and the two sites in isosorbide molecules. The batches
      differed from each other in terms of (i) the POE sorbitan stearate/POE sorbitan
      palmitate ratios (batch 1, 3:2 and batch 2, 4:5), (ii) the ratio of sorbitans to
      isosorbides (batch 1, 2:3; batch 2, 7:13); and (iii) the acid values (batch 1,
      3.1; batch 2, 0). It is concluded that liquid chromatography combined with
      electrospray mass spectrometry and ion trap separation is a useful tool for
      establishing the compositional profile of different batches of Tweens. (1)H NMR
      could provide a simple and rapid pharmacopoeial test for the ratio of sorbitan to
      isosorbide in Tweens.

PMID- 16280225
TI  - Validation of a reverse-phase high performance liquid chromatographic method for
      concurrent assay of a weak base (salmeterol xinafoate) and a pharmacologically
      active steroid (fluticasone propionate).
AB  - The analysis of weakly basic drugs such as salmeterol xinafoate (SX) by reverse
      phase liquid chromatography remains a problem, particularly when present in
      combination with other drugs such as steroids and weak acids. This study
      describes the validation of an assay for a weakly basic drug, salmeterol (SB),
      its weakly acidic counter-ion, 1-hydroxy-2-naphthoic acid (XA), and the neutral
      glucocorticoid, fluticasone propionate (FP) using a second-generation silica
      stationary phase (Inertsil ODS-2). The assay utilized an Inertsil ODS-2 base
      deactivated 250 mm x 4.6mm, 5 microm HPLC column, with 75:25 methanol:0.6%
      aqueous ammonium acetate as the mobile phase. Under these near neutral
      conditions, SB demonstrated a good peak shape (tailing factor=1.21+/-0.02, n=85).
      The method provided a short analysis time: XA, t(R)=2.96 min; SB, t(R)=5.23 min
      and FP, t(R)=7.01 min. The assay displayed good sensitivity for both XA (LOD for
      SX=0.22 microgmL(-1)) and SB (LOD for SX=0.26 microgmL(-1)). The limit of
      detection for FP was 0.19 microgmL(-1). Neither of the drugs was found to
      interfere in the determination of the other and the assay accuracy (% recovery)
      was high (the recoveries were: 99.58+/-1.85% for XA, 99.49+/-1.88% for SB and
      100.24+/-1.28% for FP). The assay reproducibility was determined with a mean
      coefficient of variance for the five calibration concentrations of XA=0.71+/
      0.18%; SB=1.11+/-0.64% and FP=0.92+/-0.14%. Analysis of a pressurized metered
      dose inhaler formulation demonstrated recovery of the analytes that are within
      pharmacopoeial limits. It was shown that RP-HPLC was suitable for the high
      throughput analysis of the combination of SX and FP.

PMID- 16280226
TI  - Online hyphenated liquid chromatography-nuclear magnetic resonance spectroscopy
      mass spectrometry for drug metabolite and nature product analysis.
AB  - Screening analysis that aims at rapidly distinguishing new molecules in the
      presence of a large number of known compounds becomes increasingly important in
      the fields of drug metabolite profiling and nature product investigation. In the
      past decade, online-coupled liquid chromatography-nuclear magnetic resonance
      spectroscopy-mass spectrometry (LC-NMR-MS) has emerged as a powerful tool for the
      detection and identification of known and, more important, emerging compounds in
      complex clinical, pharmaceutical samples and nature product extracts, due to the
      complementary information provided by the two detectors for unambiguous structure
      elucidation. This review discusses the practical conditions under which LC-NMR-MS
      is suitable as a routine tool for unknown analysis, as well as the fundamental
      concepts and their advantage aspects. Particular attention is paid to its major
      operating parameters that include the instrumental configurations, working modes,
      NMR probe improvement and LC mobile phase selection. Finally, the recent
      applications of LC-NMR-MS to clinical metabolite and nature product analysis are
      summarized which have shown the benefit of this promising hyphenated technique.

PMID- 16280228
TI  - Determination of omeprazole, hydroxyomeprazole and omeprazole sulfone using
      automated solid phase extraction and micellar electrokinetic capillary
      chromatography.
AB  - A sensitive method for the determination of omeprazole and its metabolites has
      been developed. It involves an automated solid phase extraction (SPE) procedure
      and capillary electrophoresis with UV detection. Omeprazole, hydroxyomeprazole
      and omeprazole sulfone could be separated by micellar electrokinetic capillary
      chromatography using a background electrolyte composed of 20 mM borate buffer and
      30 mM sodium dodecyl sulfate, pH 9.5. The isolation of omeprazole and its
      metabolites from plasma was automatically accomplished with an original SPE
      procedure using surface-modified styrene-divinylbenzene polymer cartridges. Good
      recovery data and satisfactory precision values were obtained. Responses were
      linear for the three analytes, from 0.08 to 2.0 microg/mL of plasma. Intra- and
      inter-day precision values of about 1.6% R.S.D. (n=10) and 2.5% R.S.D. (n=36),
      respectively, were obtained. The method is highly robust and no breakdown of the
      current or capillary blockages were observed during several weeks of operation.
      The validated method was applied to the determination of omeprazole in
      pharmaceutical preparations and for the analysis of plasma samples obtained from
      three volunteers who received oral doses of omeprazole.

PMID- 16280227
TI  - Quantitative determination of diclofenac sodium and aminophylline in injection
      solutions by FT-Raman spectroscopy.
AB  - The FT-Raman quantification of diclofenac sodium and aminophylline commercial
      injection solutions was performed. The efficiency of various spectra treatment
      procedures including classical univariate intensity ratio and multivariate
      partial least squares (PLS) and principal component regression (PCR) methods was
      compared. First, the calibration models were built using unnormalised spectra.
      Next, spectra normalised by the intensity of a selected band of CH(3)CN added as
      an internal standard to the studied samples were utilised. To compare the
      predictive ability of the models constructed, the relative standard error of
      prediction (RSEP) was calculated. The errors found for multivariate calibrations
      were a few times smaller than those for the univariate ones. Usually, the most
      effective was the PLS method, for which RSEP values of the order of 1-2% for
      calibration and 2-3% for testing data sets were obtained. Four commercial
      preparations of diclofenac sodium and one of aminophylline containing by weight,
      2.4% of the active pharmaceutical ingredient (API) were quantified applying the
      developed models. Concentrations found from the Raman data analysis correlate
      with the declared values and the results of reference analyses. For the studied
      diclofenac sodium solutions they amount to 99.2-101.2% of the former and 101.2
      102.4% of the latter quantities for the PLS models optimised for each medicine
      based on unnormalised spectra. These values for the aminophylline preparation
      were found to be 101.0 and 99.1%, respectively. It shows that the proposed
      procedure based on the chemometric treatment of FT-Raman spectra can be a fast
      and convenient alternative to the standard pharmacopoeial procedures of API
      quantification even in relatively diluted injection solutions.

PMID- 16280229
TI  - Determination of the iron state in ferrous iron containing vitamins and dietary
      supplements: application of Mossbauer spectroscopy.
AB  - Determination of the iron state in commercially manufactured iron containing
      vitamins and dietary supplements is important for evaluation of pharmaceuticals
      quality. Mossbauer (nuclear gamma-resonance) spectroscopy was used for analyzing
      the iron state in commercial pharmaceutical products containing ferrous fumarate
      (FeC(4)H(2)O(4)), ferrous sulfate (FeSO(4)), ferrous bisglycinate chelate
      (Ferrochel) and ferrous iron (hydrolyzed protein chelate). Mossbauer parameters
      and the iron states were determined for iron compounds in the studied
      pharmaceuticals. Various ferric and ferrous impurities were found in all of the
      commercial products. The quantities of ferric impurities exceeded the FDA
      limitation of 2% in products containing ferrous fumarate. The quantities of
      ferric impurities exceeded 58% and 30% in products containing ferrous
      bisglycinate chelate and ferrous iron (hydrolyzed protein chelate), respectively.
      The presence of ferrous and ferric impurities was not related to the ageing of
      the vitamins and dietary supplements. Two pharmaceutical products contained major
      iron compounds, the Mossbauer parameters of which did not correspond to the
      ferrous fumarate or ferrous bisglycinate chelate claimed by the manufacturer.

PMID- 16280230
TI  - Detecting simulation of attention deficits using reaction time tests.
AB  - The current study examined if a newly developed series of reaction time tests,
      the Computerized Tests of Information Processing (CTIP), were sensitive to
      simulation of attention deficits commonly caused by traumatic brain injury (TBI).
      The CTIP consists of three reaction time tests: Simple RT, Choice RT, and
      Semantic Search RT. These tests were administered to four groups: Control,
      Simulator, Mild TBI, and Severe TBI. Individuals attempting to simulate attention
      deficits produced longer reaction time scores, made more incorrect responses, and
      exhibited greater variability than cognitively-intact individuals and those with
      TBI. Sensitivity and specificity values were comparable or exceeded those
      obtained on the Test of Memory Malingering. As such, the CTIP offers considerable
      promise of serving as a viable malingering test that uses a distinctively
      different paradigm than the two-item, forced-choice procedure employed by
      traditional symptom validity tests.

PMID- 16280231
TI  - Factors associated with leisure activity among young adults with developmental
      disabilities.
AB  - The framework of the International Classification of Functioning, Disability, and
      Health (ICF) was applied to examine the factors associated with childhood
      impairment and leisure activity. Information on leisure activity was obtained
      using a structured questionnaire from a population-based cohort of young adults
      with childhood impairment. The results underscore the differences in leisure
      lifestyles by impairment type and severity. Activity limitations, educational
      attainment, and the acquisition of adult social roles were significant predictors
      of leisure activity. This study emphasizes the importance of improving daily
      activities, increasing attendance of postsecondary school and opportunities for
      competitive employment and participation in impairment-related programs to help
      increase the number and scope of types of leisure activities for young adults
      with developmental disabilities.

PMID- 16280232
TI  - Potential role of disc repositioning in preventing postsurgical recurrence of
      traumatogenic temporomandibular joint ankylosis: a retrospective review of 17
      consecutive cases.
AB  - The potential role of disc repositioning in preventing postsurgical recurrence of
      traumatogenic temporomandibular joint (TMJ) ankylosis was investigated. Seventeen
      cases of traumatogenic TMJ ankylosis underwent disc repositioning during
      arthroplasty. During surgery, the dislocated disc was carefully dissected outside
      the ankylotic TMJ and repositioned over the top of the condylar stump, and then
      sutured to the soft tissue of the zygomatic root. In the 22 ankylotic TMJs of the
      17 patients, dislocated discs were found in front of the ankylotic TMJ, behind
      the ankylotic TMJ or between the ramus and fossa. At the last follow-up (longer
      than 1 year) examination, interincisal opening distances ranged from 24 to 43 mm
      (mean 32.86 mm). No recurrence and TMJ symptoms were found during the period of
      follow-up. Disc repositioning in the treatment of traumatogenic TMJ ankylosis
      proves to be a feasible and effective method of preventing recurrence of this
      condition.

PMID- 16280233
TI  - Quality of life following lower third molar removal.
AB  - The objective of this study was to evaluate the quality of life (QoL) and degree
      of satisfaction among adult outpatients after surgical extraction of a lower
      third molar under local anaesthesia, and to assess the impact of thorough
      explanation of the anticipated postoperative course on their pain and daily
      activities. Ninety-two patients filled a questionnaire assessing social
      isolation, working isolation, eating ability, speaking ability, sleep impairment,
      physical appearance, discomfort at suture removal and overall satisfaction on
      days 4 and 7 after surgery. A 100-mm visual analogue scale (VAS) of pain was
      scored by the patients every day after extraction until day 7. Before extraction,
      patients were randomly allocated to one of two groups: the test group received
      detailed verbal instructions from a surgeon about the postoperative course after
      extraction of the third molars, together with a written text containing
      postoperative instructions. One day after extraction, they were asked by
      telephone about their status. The control group only received the written text
      with postoperative instructions, with a few basic oral explanations. Ninety-one
      patients (53 of them female) completed the questionnaires. The decrease in pain
      was linear over time. Men referred significantly less pain than women, but there
      were no statistically significant differences between the test and control
      groups. The test group was characterized by a significantly greater inability to
      work. Lower third molar surgery significantly affects patient quality of life and
      environment, particularly during the first 3 days after extraction.

PMID- 16280234
TI  - PET/CT in the evaluation of patients with squamous cell cancer of the head and
      neck.
AB  - The purpose of this study was to compare the findings of positron emission
      tomography (PET) with fused PET and computed tomography (CT) in patients with
      suspected locoregional and distant head and neck cancer and to evaluate the
      impact of those findings on clinical management. Studies of 25 patients were
      retrospectively evaluated. PET findings were classified as malignant, benign or
      equivocal. PET/CT findings were then similarly classified and the PET-only
      results were amended accordingly. Comparison of findings was done on lesion and
      patient levels. A total of 45 foci of increased 18F-fluorodeoxyglucose (FDG)
      uptake were noted in 18 patients. PET/CT imaging defined anatomic localization of
      41/45 lesions and clarified 6/10 equivocal PET findings. Additional information
      was provided by PET/CT regarding 9/45 (20%) of the lesions. PET/CT significantly
      affected patient management in 3/25 patients (12%) by limiting the extent of
      disease in one and excluding viable disease in two others. The accuracy of PET/CT
      was 88%, the sensitivity 100% and the specificity was 77%. The negative
      predictive value was 100% in this combined group of patients with locoregional
      and distant head and neck cancer. PET/CT is highly contributory for initial
      staging and in the evaluation of patients with suspected recurrent SCC of the
      head and neck, in whom anatomic imaging is inconclusive due to the locoregional
      distortions rendered by surgery and radiotherapy.

PMID- 16280235
TI  - Separation of the buccal cortical plate for removal of the deeply impacted
      mandibular molars.
AB  - We describe the case of 26-year-old patient who is apprehensive for any possible
      sequelae of the deeply impacted teeth. This case shows that separation of the
      buccal plate can have availability to remove deeply impacted molars with less any
      possible complications than those of sagittal split osteotomy.

PMID- 16280236
TI  - Influence of season on prevalence of cleft lip and palate.
AB  - According to the multifactorial threshold (MFT) model, cleft lip and palate (CLP)
      result from the influence of exogenous and endogenous genetic factors. Based on
      nearly 1000 cases of cleft lip with or without cleft palate treated in the clinic
      for maxillofacial surgery of the Martin-Luther University Halle-Wittenberg during
      the period 1946-1995, we investigated the influence of season on the occurrence
      of this malformation. Seasons of the year reflect various exogenous factors that
      may be accessible to prevention. The calculated date of conception served as
      comparison value between the study group and controls. The clefts of type III
      (CLP; P = 0.48), isolated CP (P = 0.933) or male patients with clefts of type I
      showed no significant deviation from the distribution in the control group over
      the year. We proved a significant maximum in spring, summer and autumn and a
      minimum in winter for the conception date of female patients with type I clefts
      (P = 0.033, relative risk = 2.6). Some of the seasonal factors implicated in the
      aetiology that play a role in the development of clefts could be:

PMID- 16280237
TI  - Criteria for trismus in head and neck oncology.
AB  - The aim of this study was to determine a functional cut-off point for trismus in
      head and neck oncology. In total, 89 patients (13 dentate, 30 partially dentate
      and 46 edentulous) treated for cancer of the oral cavity or oropharynx were asked
      whether they experienced a limited mouth opening. The mandibular function
      impairment questionnaire (MFIQ) was filled out and mouth opening was measured.
      The proportion correctly predicted (proportion true positives+proportion true
      negatives) was calculated. For cut-off points from 25 to 45 mm, differences in
      MFIQ scores of the restricted and non-restricted groups were analyzed. A receiver
      operating curve was constructed. The proportion correctly predicted was highest
      for cut-off point <or=35 mm (0.81), with a sensitivity of 0.71 and a specificity
      of 0.98. Differences in perceived mandibular function impairments were
      significant for all cut-off points of 35 mm or less. For the total group, the
      area under curve was 0.87. For the subgroups of dentate, partially dentate and
      edentulous patients, no consistent cut-off points could be found on the basis of
      the proportion correctly predicted and the significance of the difference in MFIQ
      scores. A mouth opening of <or=35 mm is a functional cut-off point for trismus in
      head and neck oncology patients.

PMID- 16280238
TI  - Rhino-orbitocerebral entomophthoramycosis.
AB  - Conidiobolus coronatus is recognized as a human pathogen causing subcutaneous
      fungal infection of the face in immunocompetent patients. The disease process is
      usually benign. We report, what we believe to be the first case of intracranial
      extension of C. coronatus producing rhino-orbitocerebral syndrome, and subsequent
      dissemination of C. coronatus in an immunocompetent patient.

PMID- 16280239
TI  - Correlation between reduction of syndecan-1 expression and clinico-pathological
      parameters in squamous cell carcinoma of tongue.
AB  - We examined expression of syndecan-1 in squamous cell carcinoma (SCC) of tongue
      using immunohistochemistry. Forty-three cases of SCC arising in lateral border of
      tongue were investigated. From the immunohistochemical staining pattern, the
      cases were divided into two groups based on expression of syndecan-1 at the supra
      peripheral cells of the tumor nest: Group A, completely or mainly positive; Group
      B, sporadically positive or negative. Most poorly differentiated SCC cases were
      classified into Group B (81.8%). The number of Group B cases in T1-2 was
      different from that in T3-4. The number of cases where syndecan-1 expression was
      reduced was much greater in T3-4, and represented the majority of Group B
      (86.7%). More than 80% of Grade 4D cases were in Group B (83.3%) based on the
      Yamamoto-Kohama criteria. These results indicate that reduction of syndecan-1
      correlates to histological grade, tumor size and mode of invasion in tongue SCC.

PMID- 16280240
TI  - Intratumoural expression of thymidylate synthase is an independent predictor of
      prognosis in patients with squamous cell carcinoma of the tongue: results from a
      retrospective study.
AB  - The aim of this study was to assess the importance of immunohistochemical
      thymidylate synthase (TS) expression level as a prognostic marker in tongue
      cancer patients. In 140 patients with primary squamous cell carcinoma (SCC) of
      the tongue, intratumoural TS expression was evaluated by immunohistochemistry.
      The level of TS expression was determined by a semiquantitative scoring system,
      ranging from 1+ to 3+ according to the ratio of TS-positive cells. Of 140
      patients, 64 (45.7%), 49 (35.0%) and 27 (19.3%) were assessed as 1+, 2+ and 3+,
      respectively. Univariate analyses demonstrated that both disease-free survival
      (DFS) and overall survival (OS) were significantly lower in patients with a TS 3+
      tumour than in those with a TS 1+/2+ tumour (DFS: P = 0.0082, OS: P = 0.0100). In
      a multivariate analysis using the Cox regression model, cervical lymph-node
      status and TS expression level were selected as independent factors for DFS and
      OS. Maintenance adjuvant chemotherapy by oral 5-fluorouracil (5-FU) significantly
      improved DFS and OS in patients with a TS 1+/2+ tumour (DFS: P = 0.0027, OS: P =
      0.0398). These data suggest that the level of immunohistochemical TS expression
      is an independent prognosticator in patients with tongue SCC, and may be useful
      in the selection of patients who would benefit from oral 5-FU adjuvant
      chemotherapy.

PMID- 16280241
TI  - Extended antimicrobial resistance screening of the dominant faecal Escherichia
      coli and of rare resistant clones.
AB  - Fifty faecal samples from healthy adults were grown on MacConkey agar and three
      pink colonies were subcultured, identified to species level and their
      antimicrobial susceptibility determined. Forty-seven samples yielded 141 isolates
      of Escherichia coli that were susceptible to most antimicrobials. Resistance was
      noted for ampicillin (30.5%), chloramphenicol (12.1%), tetracycline (23.4%),
      trimethoprim (24.8%) and co-trimoxazole (22.7%). A direct faecal plating method
      was used for extended resistance screening with E. coli as the indicator
      organism. Zone breakpoints were determined using normalised resistance
      interpretation and gave similar susceptibility results. Eighty-eight isolates of
      E. coli from within the zones of inhibition revealed four times more
      antimicrobial resistance. Extended antimicrobial resistance screening both
      provides the susceptibility profile of the dominant E. coli isolate and detects
      greater resistance in rare isolates.

PMID- 16280242
TI  - Evaluation of oxazaborolidine activity on Streptococcus mutans biofilm formation.
AB  - Dental diseases are among the most prevalent afflictions of humankind. These
      diseases are associated with the formation of biofilms harbouring pathogenic
      bacteria. Eight different derivatives of oxazaborolidines were synthesised and
      evaluated for their affect on Streptococcus mutans adhesion and biofilm
      formation. Structure-activity relationship was observed. The B-butyl moiety of
      the oxazaborolidines contributed an anti-adhesion effect for all derivatives,
      whilst its effect diminished when the boron atom was incorporated in a fused
      heterocyclic ring. The B-phenyl group induced bacterial adhesion in all tested
      compounds Oxazaborolidines may serve as novel agents for affecting oral biofilm
      formation. Moreover, the ability to alter the oxazaborolidine molecule and thus
      affect biofilms offers an excellent opportunity to study biofilm formation.

PMID- 16280243
TI  - Relationships between antimicrobial use and antimicrobial resistance in Gram
      negative bacteria causing nosocomial infections from 1991-2003 at a university
      hospital in Taiwan.
AB  - This study was conducted to evaluate the relationship between antimicrobial
      resistance and antimicrobial use in a university hospital in Taiwan. Disk
      susceptibility data of Escherichia coli, Klebsiella pneumoniae, Enterobacter
      cloacae, Serratia marcescens, Proteus spp., Pseudomonas aeruginosa, Acinetobacter
      spp., Stenotrophomonas maltophilia and other non-fermentative Gram-negative
      bacilli causing nosocomial infections were evaluated. Data on annual patient-days
      and annual consumption (defined daily dose (DDD) per 1000 patient-days) of
      extended-spectrum cephalosporins (cefotaxime, ceftriaxone, ceftazidime, flumoxef,
      cefepime and cefpirome), beta-lactam-beta-lactamase inhibitor combinations
      (ticarcillin/clavulanic acid and piperacillin/tazobactam), carbapenems (imipenem
      and meropenem), aminoglycosides (amikacin, gentamicin and tobramycin),
      fluoroquinolones (ciprofloxacin (oral and injectable) and oral levofloxacin and
      moxifloxacin) from 1991 to 2003 were analysed. Increasing trends of incidences of
      several of these bacteria causing all nosocomial infections or nosocomial
      bloodstream infections were noted from 1991 to 2003. The annual patient-days of
      the hospital significantly increased, from 360210 in 1991 to 672676 in 2002
      (linear regression analysis, P < 0.05), but slightly decreased in 2003 (629168)
      owing to the severe acute respiratory syndrome epidemic in Taiwan. The rise in
      cefotaxime-resistant or ciprofloxacin-resistant E. coli and meropenem-resistant
      P. aeruginosa was significantly correlated with increased consumption of extended
      spectrum cephalosporins, beta-lactam-beta-lactamase inhibitor combinations,
      carbapenems, fluoroquinolones and aminoglycosides (for ciprofloxacin-resistant E.
      coli and meropenem-resistant P. aeruginosa only) in the hospital (Pearson's
      correlation coefficient, r > 0.72 (or < -0.72) and P-value < 0.05). Increased
      ciprofloxacin-resistant K. pneumoniae and meropenem-resistant Acinetobacter spp.
      was significantly associated with the increased usage of extended-spectrum
      cephalosporins but not with the other four classes of antibiotics. This 13-year
      study in a hospital demonstrated significant changes in antimicrobial use, which
      may have affected antimicrobial resistance in certain Gram-negative bacteria at
      the hospital.

PMID- 16280244
TI  - Intrapulmonary pharmacokinetics and pharmacodynamics of meropenem.
AB  - The objective of this study was to determine the plasma and intrapulmonary
      pharmacokinetic parameters of intravenously administered meropenem in healthy
      volunteers. Four doses of 0.5 g, 1.0 g or 2.0 g meropenem were administered
      intravenously to 20, 20 and 8 healthy adult subjects, respectively. Standardised
      bronchoscopy and timed bronchoalveolar lavage (BAL) were performed following
      administration of the last dose. Blood was obtained for drug assay prior to drug
      administration and at the time of BAL. Meropenem was measured in plasma, BAL
      fluid and alveolar cells (ACs) using a combined high pressure liquid
      chromatographic-mass spectrometric technique. Plasma, epithelial lining fluid
      (ELF) and AC pharmacokinetics were derived using non-compartmental methods.
      Cmax/MIC90 (where Cmax is the maximum plasma concentration and MIC90 is the
      minimum inhibitory concentration required to inhibit 90% of the pathogen),
      AUC/MIC90 (where AUC is the area under the curve for the mean concentration-time
      data), intrapulmonary drug exposure ratios and percent time above MIC90 during
      the dosing interval (%T > MIC90) were calculated for common respiratory pathogens
      with MIC90 values of 0.12-4 microg/mL. In the 0.5 g dose group, the Cmax (mean+/
      S.D.), AUC(0-8 h) and half-life for plasma were, respectively, 25.8+/-5.8
      microg/mL, 28.57 microg h/mL and 0.77 h; for ELF the values were 5.3+/-2.5
      microg/mL, 12.27 microg h/mL and 1.51 h; and for ACs the values were 1.0+/-0.5
      microg/mL, 4.30 microg h/mL and 2.61 h. In the 1.0 g dose group, the Cmax, AUC(0
      8 h) and half-life for plasma were, respectively, 53.5+/-19.7 microg/mL, 55.49
      microg h/mL and 1.31 h; for ELF the values were 7.7+/-3.1 microg/mL, 15.34 microg
      h/mL and 0.95 h; and for ACs the values were 5.0+/-3.4 microg/mL, 14.07 microg
      h/mL and 2.17 h. In the 2.0 g dose group, the Cmax, AUC(0-8 h) and half-life for
      plasma were, respectively 131.7+/-18.2 microg/mL, 156.7 microg h/mL and 0.89 h.
      The time above MIC in plasma ranged between 28% and 78% for the 0.5 g dose and
      between 45% and 100% for the 1.0 g and 2.0 g doses. In ELF, the time above MIC
      ranged from 18% to 100% for the 0.5 g dose and from 25% to 88% for the 1.0 g
      dose. In ACs, the time above MIC ranged from 0% to 100% for the 0.5 g dose and
      from 24% to 100% for the 1.0 g dose. Time above MIC in ELF and ACs for the 2.0 g
      dose was not calculated because of sample degradation. The prolonged T > MIC90
      and high intrapulmonary drug concentrations following every 8 h administration of
      0.5-2.0 g doses of meropenem are favourable for the treatment of common
      respiratory pathogens.

PMID- 16280245
TI  - Nephrotoxicity of intravenous colistin: a prospective evaluation.
AB  - Twenty-one patients who received intravenous colistimethate sodium (CMS) for at
      least 7 days for the treatment of multidrug-resistant Gram-negative bacterial
      infections were included in a prospective cohort study at 'Henry Dunant' Hospital
      in Athens, Greece. The mean (+/- standard deviation) and median daily doses,
      cumulative doses and duration of treatment of intravenous CMS were, respectively,
      5.5 (+/- 1.9) and 6 million IU, 90.2 (+/- 52.0) and 72 million IU, and 17.7 (+/-
      11.7) and 15 days (range 7-54 days). Three patients (14.3%) developed
      nephrotoxicity during treatment with CMS. The cumulative dose of administered CMS
      was statistically correlated with the difference in values of serum creatinine
      between the end and start of CMS treatment (r = 0.6, P = 0.004 by Spearman's
      test).

PMID- 16280246
TI  - Interleukin-18 primes human basophilic KU812 cells for higher leukotriene
      synthesis.
AB  - The human basophilic cell line KU812 that is an established tool for studying the
      function of human basophils, is differentiated into mature basophils by
      interleukin (IL-3) or other agents. However, whether leukotrienes (LTs)-synthesis
      is affected by cytokines in KU812 cells remains unknown. KU812 cells were
      incubated with IL-3, IL-4, IL-6, IL-13 or IL-18 for up to 14 days. The A23187
      stimulated- and IgE cross-linked-synthesis of LTC(4) and LTB(4) were measured
      using an enzyme immunoassay (EIA). The expression of messenger RNA (mRNA) for LT
      synthesizing enzymes was examined by reverse transcriptase polymerase chain
      reaction (RT-PCR), and the expression of 5-lipoxygenase (5-LO) was examined by
      immunostaining. Incubation with IL-3 (10 ng/ml) and IL-18 (10 ng/ml) induced the
      expression of 5-LO. A23187stimulated LT-synthesis and IgE cross-linked LT
      synthesis were enhanced after incubation with IL-3 or IL-18. These results
      indicated that IL-3 and IL-18 primed human basophils for higher LT-synthesis.
      Thus, both IL-3 and IL-18 might be important factors for regulating LT-synthesis
      during the differentiation of human basophils.

PMID- 16280247
TI  - Selective serotonin re-uptake inhibition attenuates evoked glutamate release in
      the dorsal horn of the anaesthetised rat in vivo.
AB  - Augmentation of serotonergic neurotransmission at the level of the dorsal spinal
      cord is proposed to contribute to the analgesic activity of selective serotonin
      (5-HT) reuptake inhibitors (SSRIs). In this study we have utilised microdialysis
      perfusion to determine the effect of two structurally unrelated SSRIs on
      depolarisation-induced aspartate and glutamate release in the dorsal spinal cord
      of the anaesthetised rat. Perfusion with artificial extracellular fluid
      containing 45 mM potassium produced a significant increase in aspartate and
      glutamate efflux. Sensitivity, at least in part, to antagonism of calcium entry
      by high extracellular Mg2+ indicated a neuronal origin for a proportion of
      stimulated release. Reverse dialysis of paroxetine (1-30 microM) reduced the
      increase in glutamate in a concentration dependent manner, with a significant
      reduction evident following inclusion in the perfusate of 30 microM.
      Administration of an equi-potent dose of citalopram (300 micoM) also reduced
      depolarisation induced glutamate release. Aspartate levels tended to decrease in
      the presence of paroxetine and citalopram, but this trend did not reach
      significance. Co-perfusion of paroxetine (30 microM) with the selective 5-HT(1A)
      receptor antagonist WAY 100635 (100 microM) did not prevent the reduction in
      depolarisation induced glutamate efflux. These results demonstrate that local
      administration of SSRIs has an inhibitory influence on evoked release of
      glutamate in the dorsal horn. This could indicate regulation of excitatory
      neurotransmission mediated through augmented serotonergic neurotransmission and
      activation of a serotonergic receptor other than the 1A subtype. Alternatively,
      direct inhibition with voltage dependent calcium channels, potentially a property
      intrinsic to molecules with high selectivity for the 5-HT transporter, may
      underlie this effect.

PMID- 16280248
TI  - Accuracy and reliability of maternal recall of infant birth weight among older
      women.
AB  - PURPOSE: We assessed the accuracy and reliability of maternal recall of infant
      birth weight 35 to 70 years after delivery. METHODS: A total of 120 well
      functioning women (mean age 80 years; 45% Black) reported the birth weight for
      each live birth and then provided documentation of birth weights (n = 22) or
      reported birth weights a second time (n = 98). RESULTS: Agreement between
      recalled and documented birth weights was high for first births (ICC = 0.96) but
      moderate for subsequent births (ICC = 0.59). Maternal recall was highly reliable
      for first births (r = 0.95) and subsequent births (r = 0.87), and reliability
      remained high when considered separately by race, education, income, and age.
      CONCLUSION: Women report accurate and reliable infant birth-weight data an
      average of 57 years after delivery, and recall is particularly precise for first
      births.

PMID- 16280250
TI  - Long-term efficacy of levetiracetam for partial seizures.
AB  - OBJECTIVE: To obtain descriptive safety and efficacy data for long-term
      levetiracetam therapy and to allow patients benefiting from add-on levetiracetam
      to continue treatment until the drug was available commercially. METHODS: This
      long-term, noncomparative, open-label, follow-up study was conducted at 36 US
      sites. Patients with refractory partial epileptic seizures were eligible if they
      had benefited from add-on levetiracetam therapy in a previous study and wished to
      continue treatment. The levetiracetam dose was individualized over the range of
      1,000-4,000 mg/day. Withdrawal of concomitant AEDs to allow levetiracetam
      monotherapy was permitted. Patients were evaluated every 12 weeks and followed
      for up to 4 years. Median total seizure frequency per week was the primary
      efficacy variable. RESULTS: A total of 280 subjects, most of whom had refractory
      partial seizures with or without secondary generalization, were evaluated. Most
      were receiving either one (34.6%) or two (53.2%) concomitant antiepileptic drugs
      (AEDs) at entry. Overall, 199 (71.1%) subjects completed the study and 81 (28.9%)
      withdrew prematurely, most commonly due to loss or lack of efficacy or adverse
      events. The median total seizure frequency per week (0.7 at the selection visit)
      remained stable. The probability of being seizure-free during the first 12 weeks
      was 13.4% and 3.7% by week 216. Twenty-five (8.9%) subjects received
      levetiracetam monotherapy for at least 100 days. Levetiracetam was safe and well
      tolerated; the most common levetiracetam-related adverse events were dizziness
      (6.8%), convulsion (5.7%), and somnolence (5.0%). CONCLUSION: Efficacy and safety
      were maintained during long-term levetiracetam treatment of refractory partial
      seizures.

PMID- 16280249
TI  - Integrated in vivo pharmacology using an instrumented, unrestrained and conscious
      rat platform: application to rat models of diabetes.
AB  - INTRODUCTION: We define the technical and methodological aspects that led to a
      practical and reproducible biological in vivo platform allowing the measurement
      of more than 65 physiobiochemical parameters on a daily basis in freely moving
      conscious animals. Such a platform presents the ability to unleash incremental
      information in the hands of modern-day pharmacologists and physiologists.
      METHODS: To validate this platform, we fully characterized three rat models of
      Type 1 and Type 2 diabetes and their respective controls. Control, streptozotocin
      and alloxan-diabetic Wistar rats in addition to ZDF-Lean and ZDF-Fatty rats were
      chronically implanted with an arterial catheter and kept in metabolic cages. The
      catheter was connected to a minipump infusing saline at a constant rate to
      maintain patency and used to collect blood and measure hemodynamic parameters on
      a daily basis. RESULTS: Catheter implantation was successful in over 95% of
      animals and catheter patency was successfully maintained for 30 days in about 75%
      of animals. The three diabetic rat strains showed elevations in food and water
      consumption, urinary output, plasma glucose, blood urea nitrogen, triglycerides
      and cholesterol. The two Type I models also showed a depressed body weight and
      hemodynamic function. The STZ model differed from the alloxan-model by elevations
      in liver enzyme activities (AST, ALT, and bilirubin) and a more severe
      dyslipidemia (triglycerides and total cholesterol). The ZDF-Fatty rats
      distinguished themselves by higher body weight and elevated white blood cell
      counts. DISCUSSION: This integrated platform represents a significant improvement
      in standard in vivo evaluations and could greatly improve the pace of development
      of potential new drugs.

PMID- 16280251
TI  - Non-linear elastic properties of the lingual and facial tissues assessed by
      indentation technique. Application to the biomechanics of speech production.
AB  - This paper aims at characterizing the mechanical behavior of two human anatomical
      structures, namely the tongue and the cheek. For this, an indentation experiment
      was provided, by measuring the mechanical response of tongue and cheek tissues
      removed from the fresh cadaver of a 74 year old woman. Non-linear relationships
      were observed between the force applied to the tissues and the corresponding
      displacements. To infer the mechanical constitutive laws from these measurements,
      a finite element (FE) analysis was provided. This analysis aimed at simulating
      the indentation experiment. An optimization process was used to determine the FE
      constitutive laws that provided the non-linear force/displacements observed
      during the indentation experiments. The tongue constitutive law was used for
      simulations provided by a 3D FE biomechanical model of the human tongue. This
      dynamical model was designed to study speech production. Given a set of tongue
      muscular commands, which levels correspond to the force classically measured
      during speech production, the FE model successfully simulated the main tongue
      movements observed during speech data.

PMID- 16280252
TI  - Social space, social class and Bourdieu: health inequalities in British Columbia,
      Canada.
AB  - This article adopts Pierre Bourdieu's cultural-structuralist approach to
      conceptualizing and identifying social classes in social space and seeks to
      identify health effects of class in one Canadian province. Utilizing data from an
      original questionnaire survey of randomly selected adults from 25 communities in
      British Columbia, social (class) groupings defined by cultural tastes and
      dispositions, lifestyle practices, social background, educational capital,
      economic capital, social capital and occupational categories are presented in
      visual mappings of social space constructed by use of exploratory multiple
      correspondence analysis techniques. Indicators of physical and mental health are
      then situated within this social space, enabling speculations pertaining to
      health effects of social class in British Columbia.

PMID- 16280253
TI  - Signalling via the reperfusion injury signalling kinase (RISK) pathway links
      closure of the mitochondrial permeability transition pore to cardioprotection.
AB  - Post-ischemic interventions that activate phosphatidylinositol-3-OH kinase (PI3K)
      Akt or ERK1/2 pro-survival kinases (the so-called "reperfusion injury signalling
      kinase (RISK) pathway") during the first few minutes of reperfusion protect
      against lethal reperfusion-induced injury. We have previously shown that insulin
      protects against reperfusion-induced injury via activation of the PI3K-Akt
      pathway. In addition, opening of the mitochondrial permeability transition pore
      (mPTP) at the time of reperfusion is a major determinant of lethal reperfusion
      induced injury, and pharmacologically inhibiting it is cardioprotective. In this
      study, we examined the relationship between the pro-survival kinase pathways and
      mPTP opening. Specifically, we tested the hypothesis that activation of the pro
      survival kinase pathway by insulin protects cardiomyocytes by reducing the
      probability of mPTP opening upon reperfusion. Laser illumination of the
      fluorophore, tetramethyl rhodamine methyl ester (TMRM), was used to induce
      oxidative stress in the preparation of adult rat ventricular cardiomyocytes.
      Maintained illumination ultimately induces mPTP opening, detected as a global
      mitochondrial depolarization, followed by ATP depletion and rigor contracture.
      Insulin significantly delayed mPTP opening by a factor of approximately 1.7-fold
      (P<0.001). The effect of insulin was prevented by Wortmannin and by LY-294002,
      inhibitors of the PI3K pathway, by SH-6, a selective inhibitor of Akt, and by L
      NAME, an inhibitor of nitric oxide production. The expression of a dominant
      negative construct of Akt eliminated the effect of insulin in delaying mPTP
      opening in a cardiac cell line. Furthermore, the overexpression of constitutively
      active Akt was sufficient to maximally delay mPTP opening. These results indicate
      that activation of the PI3K-Akt pro-survival kinase pathway inhibits opening of
      the mPTP, and demonstrate an important link between the survival kinases and the
      mPTP.

PMID- 16280254
TI  - Developing salt-tolerant crop plants: challenges and opportunities.
AB  - Soil salinity, one of the major abiotic stresses reducing agricultural
      productivity, affects large terrestrial areas of the world; the need to produce
      salt-tolerant crops is evident. Two main approaches are being used to improve
      salt tolerance: (i) the exploitation of natural genetic variations, either
      through direct selection in stressful environments or through mapping
      quantitative trait loci and subsequent marker-assisted selection; and (ii) the
      generation of transgenic plants to introduce novel genes or to alter expression
      levels of the existing genes to affect the degree of salt stress tolerance. Here,
      we discuss the challenges and opportunities provided by recently developed
      functional tools for the development of salt-tolerant crops.

PMID- 16280255
TI  - Prediction of early and confirmed virological response by genotypic inhibitory
      quotients for lopinavir in patients naive for lopinavir with limited exposure to
      previous protease inhibitors.
AB  - OBJECTIVE: To determine the impact of genotypic inhibitory quotient (GIQ) for
      lopinavir (LPV) in patients failing HAART with limited antiretroviral exposure.
      DESIGN: Retrospective analysis of a prospective trial. METHODS: Lopinavir GIQ was
      calculated as the ratio between the mean trough concentration (C(trough)) and the
      number of protease mutations using eight different HIV drug resistance mutation
      lists or algorithms. Early (by week 12) and confirmed (up to week 24) virological
      response (HIV-RNA< 400 copies/mL, ECVR) was used as dependent variable in
      logistic regression model. RESULTS: Seventy-one of 109 (65%) patients achieved
      ECVR. At multivariable logistic regression analysis, each mug/mL increase of GIQ
      was correlated with increasing probability of ECVR as far as the following
      mutations were computed: multi-protease inhibitor (PI) associated mutations
      listed by IAS (OR=1.17; 95% CI=0.99-1.39; P=0.058), mutations associated with LPV
      resistance by ANRS algorithm (OR=1.21; 95% CI=1.02-1.44; P=0.03), major mutations
      associated with LPV resistance by Stanford database (OR=1.16; 95% CI=1-1.35;
      P=0.05), and the whole set of mutations associated with LPV resistance in the
      same database (OR=1.22; 95% CI=1.02-1.46; P=0.03). Using ROC curve method, a
      specific threshold GIQ was assessed, above which this parameter could predict
      ECVR with the highest sensitivity (74.6% with GIQ obtained through Stanford LPV
      mutations) or specificity (89.5% with GIQ obtained through ANRS LPV mutations).
      CONCLUSIONS: Our results suggest that increasing GIQ can improve virological
      outcome even in patients with limited exposure to PIs. Further studies are
      necessary to understand what HIV protease mutations should be considered and
      whether such mutations should be weighted differently to improve LPV GIQ
      predictive value.

PMID- 16280256
TI  - Rhinovirus/enterovirus RNA in tonsillar tissue of children with tonsillar
      disease.
AB  - BACKGROUND: Human rhinoviruses (HRVs) together with the closely related human
      enteroviruses (HEVs) cause most of the acute respiratory illnesses throughout the
      year. HRVs have been detected in most parts of the respiratory tract but not in
      pharyngeal tonsils. OBJECTIVES: We aimed to find out whether HRVs were detectable
      in tonsillar tissue and if their presence correlated to the tonsillar disease.
      STUDY DESIGN: Thirty-three tonsillar samples collected in February-March 2003
      from children with no acute respiratory symptoms were studied with HRV in situ
      hybridization (HRV-ISH). Ten tonsillar samples were further examined in a
      separate laboratory by two different reverse transcription polymerase chain
      reaction (RT-PCR) methods designed for detection of HRV/HEV RNA. RESULTS: Twenty
      of the 33 samples (62%) were positive by HRV-ISH. Five positive and five negative
      HRV-ISH samples were investigated by two different PCR methods. HRV/HEV RNA was
      detected in 9 of the 10 specimens by a hanging drop-nested PCR. One HRV-ISH
      negative sample was positive by a conventional non-nested PCR. One of the samples
      studied by all three methods, from a patient with recurrent tonsillitis, had no
      detectable HRV/HEV RNA. Positive result in HRV-ISH did not correlate
      significantly with underlying tonsillar disease, history of respiratory
      infections or bronchial asthma. Altogether HRV/HEV RNA was detected in 75% of the
      tonsils with no correlation to patients' operation indication or history of
      respiratory diseases. CONCLUSIONS: In February-March, HRV/HEV RNA was frequently
      found in tonsillar tissue in children irrespective of the tonsillar pathology.
      Whether detection of the RNA is a marker of chronic infection or is merely
      remnant of past infection is not known.

PMID- 16280257
TI  - Allogeneic hematopoietic cell transplantation following nonmyeloablative
      conditioning as treatment for hematologic malignancies and inherited blood
      disorders.
AB  - Allogeneic hematopoietic cell transplantation (HCT) after myeloablative
      conditioning regimens has been an effective treatment for many patients with
      hematologic malignancies or inherited blood disorders. Unfortunately, such
      regimens have been associated with significant toxicity, limiting their use to
      otherwise healthy, relatively young patients. In an attempt to extend treatment
      by allogeneic HCT to older patients and those with comorbid conditions, several
      groups of investigators have developed reduced-intensity or truly
      nonmyeloablative conditioning regimens, lacking such toxicity. Analogous to
      conventional regimens, reduced-intensity regimens both eliminated host-versus
      graft (rejection) reactions and produced major anti-tumor effects. In contrast,
      nonmyeloablative regimens have relied on optimizing both pre-and posttransplant
      immunosuppression to overcome host-versus-graft reactions, while anti-tumor
      responses have depended mainly on immune-mediated graft-versus-tumor effects. In
      this review, we define reduced-intensity and truly nonmyeloablative regimens,
      describe the preclinical development and clinical application of a very low
      intensity nonmyeloablative regimen, and review results with reduced-intensity
      regimens in patients with hematologic malignancies or inherited blood disorders.

PMID- 16280258
TI  - Acute actions of marine toxin latrunculin A on the electrophysiological
      properties of cultured dorsal root ganglion neurones.
AB  - The effects of latrunculin A, isolated from the nudibranch Chromodoris sp., on
      the excitability of neonatal rat cultured dorsal root ganglion neurones were
      investigated using patch-clamp recording and Ca(2+) imaging techniques. Under
      current-clamp conditions, acute application of latrunculin A (100 microM)
      reversibly induced multiple action potential firing and significantly increased
      action potential duration. No significant effects on action potential peak
      amplitude, threshold of action potential firing, resting membrane potential and
      input resistance were observed. Under voltage-clamp conditions, significant and
      dose-dependent suppression of K(+) current was seen with 10-100 microM
      latrunculin A. Additionally, a significant difference between inhibition of the
      current measured at the peak and the end of a 100 ms voltage step was seen with
      100 microM latrunculin A. Fura-2 fluorescence Ca(2+) imaging revealed that
      latrunculin A (100 microM) significantly inhibited Ca(2+) transients evoked by
      KCl-induced depolarisation in all neurones. In 36% of DRG neurones, latrunculin A
      alone had no effect on intracellular Ca(2+). In 64% of neurones, latrunculin A
      alone evoked a transient rise in intracellular Ca(2+). Moreover, latrunculin A
      (10-100 microM) significantly inhibited the mean high voltage-activated Ca(2+)
      current. The effects of latrunculin A on action potential firing and K(+)
      currents were attenuated by intracellular phalloidin, an indication that these
      effects are mediated through actin disruption.

PMID- 16280259
TI  - Quantification of ACE inhibiting peptides in human plasma using high performance
      liquid chromatography-mass spectrometry.
AB  - An HPLC-MRM-MS method was developed for the quantification of 17 small ACE
      inhibiting (ACEI) peptides in plasma samples collected from human volunteers
      after the consumption of a peptide-enriched drink. The assay shows the high
      selectivity and sensitivity necessary to monitor small changes in the levels of
      the ACEI peptides after consumption of drinks developed to effect lowering of the
      blood pressure. Four different sample preparation methods were tested and
      evaluated. The final sample preparation method selected is simple and effective
      and consists mainly of the removal of proteins by acidification and heating,
      followed by a large volume injection. Additional sample preparation steps such as
      solid phase extraction and liquid/liquid partitioning were studied. Although they
      resulted in cleaner extracts, losses of specific peptides such as SAP were
      frequently seen. The isotope labeled form of one of the peptides to be
      quantified, [U(13)C]IPP, was used as an internal standard. The limit of detection
      of the assay is below 0.01 ng ml(-1). The limit of quantification is between 0.05
      and 0.2 ng ml(-1), which is approximately 10% of the expected peptide
      concentration in plasma based on a normal diet. The intra- and inter-day relative
      standard deviations for all peptides have shown to be below 25% and the method
      has an accuracy of better than 75%. The long-term stability is good. At least 200
      samples could be analysed before the system had to be cleaned. The assay has been
      successfully applied to blood samples collected from volunteers during a human
      trial.

PMID- 16280260
TI  - Development and validation of a rapid HPLC method for simultaneous determination
      of tramadol, and its two main metabolites in human plasma.
AB  - Tramadol, an analgesic agent, and its two main metabolites O-desmethyltramadol
      (M1) and N-desmethyltramadol (M2) were determined simultaneously in human plasma
      by a rapid and specific HPLC method. The sample preparation was a simple
      extraction with ethyl acetate. Chromatographic separation was achieved with a
      Chromolith Performance RP-18e 50 mm x 4.6 mm column, using a mixture of
      methanol:water (13:87, v/v) adjusted to pH 2.5 by phosphoric acid, in an
      isocratic mode at flow rate of 2 ml/min. Fluorescence detection (lambda(ex)=200
      nm/lambda(em)=301 nm) was used. The calibration curves were linear (r(2)>0.997)
      in the concentration range of 2.5-500 ng/ml, 1.25-500 ng/ml and 5-500 ng/ml for
      tramadol, M1 and M2, respectively. The lower limit of quantification was 2.5
      ng/ml for tramadol, 1.25 ng/ml for M1 and 5 ng/ml for M2. The within- and between
      day precisions in the measurement of QC samples at four tested concentrations
      were in the range of 2.5-9.7%, 2.5-9.9% and 5.9-11.3% for tramadol, M1 and M2,
      respectively. The developed procedure was applied to assess the pharmacokinetics
      of tramadol and its two main metabolites following administration of 100mg single
      oral dose of tramadol to healthy volunteers.

PMID- 16280261
TI  - A LC-MS/MS method to quantify the novel cholesterol lowering drug ezetimibe in
      human serum, urine and feces in healthy subjects genotyped for SLCO1B1.
AB  - Ezetimibe (Ezetrol) is a novel cholesterol lowering drug which disposition is not
      fully understood in man. We developed a selective and high-sensitive assay to
      measure serum concentration-time profiles, renal and fecal elimination of
      ezetimibe in pharmacokinetic studies. Ezetimibe glucuronide, the major metabolite
      of ezetimibe was determined by enzymatic degradation to the parent compound.
      Ezetimibe was measured after extraction with methyl tert-butyl ether using 4
      hydroxychalcone as internal standard and liquid chromatography coupled via an
      APCI interface with tandem mass spectrometry (LC-MS/MS) for detection. The
      chromatography (column XTerra) MS, C(18), 2.1 mm x 100 mm, particle size 3.5
      microm) was done isocratically with acetonitrile/water (60/40, v/v; flow rate 200
      microl/min). The MS/MS analysis was performed in the negative ion mode (m/z
      transition: ezetimibe 408-271, internal standard 223-117). The validation ranges
      for ezetimibe and total ezetimibe were as follows: serum 0.0001-0.015 microg/ml
      and 0.001-0.2 microg/ml; urine and fecal homogenate 0.025-10 microg/ml and 0.1-20
      mg/ml, respectively. The assay was successfully applied to measure ezetimibe
      disposition in two subjects genotyped for the hepatic uptake transporter SLCO1B1.

PMID- 16280262
TI  - A liquid chromatographic-mass spectrometric evidence of dihydrosanguinarine as a
      first metabolite of sanguinarine transformation in rat.
AB  - Adult rats were orally administered with a single dose of sanguinarine (10 mg SA
      per 1 kg body weight) in 1.0 ml water. In the plasma and the liver,
      dihydrosanguinarine (DHSA) was identified as a SA metabolite by high performance
      liquid chromatography-electrospray ionization mass spectrometry (HPLC/ESI-MS).
      Significantly higher levels of DHSA were found in both the plasma and the liver
      in comparison with those of SA. SA and DHSA were not detected in the urine. The
      formation of DHSA might be the first step of SA detoxification in the organism
      and its subsequent elimination in phase II reactions. Benz[c]acridine (BCA), in
      the literature cited SA metabolite, was found neither in urine nor in plasma and
      liver.

PMID- 16280263
TI  - Identification and quantitative determination of benproperine metabolites in
      human plasma and urine by liquid chromatography-tandem mass spectrometry.
AB  - Two novel metabolites of benproperine (BPP), 1-[1-methyl-2-[2
      (phenylmethyl)phenoxy]ethyl]-3-piperidinol (3-OH-BPP) and 1-[1-methyl-2-[2
      (phenylmethyl)phenoxy]ethyl]-4-piperidinol (4-OH-BPP), were confirmed by
      comparison of retention times and mass spectra with those of synthetic standards
      using liquid chromatography-tandem mass spectrometry. Selective and sensitive
      procedures were developed for the simultaneous determination of BPP, 3-OH-BPP and
      4-OH-BPP in human plasma and urine. The analytes were extracted from plasma
      sample and enzymatically hydrolyzed urine samples by liquid-liquid extraction,
      separated through a Diamonsil C(18) column (150 mm x 4.6 mm i.d.) and determined
      by tandem mass spectrometry with an electrospray ionization interface in selected
      reaction monitoring mode. Dextromethorphan was used as internal standard. The
      mobile phase consisted of acetonitrile-water-formic acid (34:66:1, v/v/v), and
      flow-rate was 0.5 ml min(-1). This method has a lower limit of quantification
      (LLOQ) of 60, 4.0 and 4.0 nmol l(-1)for BPP, 3-OH-BPP and 4-OH-BPP in plasma,
      4.9, 4.7 and 2.4 nmol l(-1) in urine, respectively. The intra- and inter-run
      precision were measured to be below 9.2%, and the accuracy was within +/-4.3% for
      the analytes. The method was successfully used to determine BPP, 3-OH-BPP and 4
      OH-BPP in plasma and urine for pharmacokinetic investigation. The results
      indicated residue of 3-OH-BPP in the body at least 192 h after an oral dose of
      BPP.

PMID- 16280264
TI  - Specific determination of threonine in biological samples by gas chromatography
      with electron capture detection.
AB  - Threonine was oxidized into acetaldehyde at 0 degrees C for 30 min with periodic
      acid. The acetaldehyde formed was converted to a hydrazone with 2,4
      dinitrophenyhydrazine. The hydrazone was extracted with n-heptane and quantified
      by gas liquid chromatography with electron capture detection. An internal
      standard, 2-amino-3-hydroxyhexanoic acid, was used. The calibration curve of
      threonine was linear up to 200 nmol in 200 microl sample solution and the
      determination limit of threonine was 1 nmol in 200 microl sample solution. The
      recoveries were 100.0, 94.0 and 100.0% from homogenates of octopus tentacles and
      blood plasma and rat livers, respectively. This method was applied to the
      determination of threonine in tissues of rats given threonine and starved
      octopuses. This threonine determination method has been used for studies on the
      metabolism of d-lactate.

PMID- 16280265
TI  - Liquid chromatography-mass spectrometry method for the determination of
      nicardipine in human plasma.
AB  - A simple and sensitive liquid chromatography-mass spectrometry method is
      described for the determination of nicardipine in human plasma. Chromatographic
      separation of the analyte was achieved on a C(18) column using a mobile phase of
      methanol, water and formic acid (320:180:0.4, v/v/v). Selected ion monitoring
      (SIM) in positive mode was used for analyte quantification at m/z 480.2 for
      nicardipine and m/z 256.4 for diphenhydramine. The run time was less than 5 min.
      The linearity over the concentration range of 0.05-20.0 ng/ml for nicardipine was
      obtained and the lower limit of quantification was 0.05 ng/ml. For each level of
      QC samples, inter-day and intra-day precisions (R.S.D.) were < or =9.3 and 11.1%,
      respectively, and accuracy (RE) was +/-4.9%. The present LC-MS method was
      successfully applied in the pharmacokinetic studies of nicardipine hydrochloride
      delayed-release tablets in two formulations after oral administration to healthy
      volunteers.

PMID- 16280266
TI  - 13C-urea breath test in the management of Helicobacterpylori infection.
AB  - The urea breath test is a noninvasive and very accurate test for the diagnosis of
      Helicobacter pylori infection. However, false negative urea breath test results
      have been reported to occur in a considerable percentage of the individuals
      taking proton pump inhibitors; the interval needed to be completely confident
      that false negative tests had been excluded has varied among the different
      studies between 6 and 14 days. The impact of H(2)-receptor antagonists on the
      accuracy of urea breath test remains controversial, although, in contrast with
      proton pump inhibitors, the data suggest that H(2)-receptor antagonists, for the
      most part, have little effect on the result of the urea breath test. The urea
      breath test does not represent a suitable tool for estimating the density of H.
      pylori colonization. The only quantitative information to be obtained from the
      urea breath test is that the higher the delta value, the lower the probability of
      a false-positive urea breath test result. Although some authors have demonstrated
      a correlation between urea breath test values and histological lesions of the
      gastric mucosa, the practical utility of this relationship remains unclear. It
      has been suggested that the pretreatment urea breath test has the potential to
      identify patients who require modification of the standard therapeutic regimen
      (for example, prolonging the duration of treatment or increasing the
      pharmacological dose when bacterial density is high), but other studies could not
      confirm this relationship. Some studies have shown that the urea breath test is
      less accurate in patients who have undergone partial gastrectomy. Finally, in
      contrast with biopsy-based methods, which are responsible for a high number of
      false-negative results when used to diagnose H. pylori infection in patients with
      upper gastrointestinal bleeding, urea breath test seems not to be negatively
      influenced by the presence of this complication.

PMID- 16280268
TI  - Extending the reach of ambulatory blood pressure monitoring: masked and resistant
      hypertension.

PMID- 16280267
TI  - Lessons for inflammatory bowel disease from rheumatology.
AB  - There are several areas of overlap between gastroenterology and rheumatology,
      some related to the side effects of drugs but others related to the similarities
      in probable pathogenic mechanisms and treatments. This is best illustrated by
      comparison between inflammatory bowel disease and rheumatoid arthritis-conditions
      of uncertain aetiology that are due to a combination of genetic and environmental
      factors and are associated with chronic inflammation in the absence of any
      clearly recognisable pathogen. Medical research is increasingly specialised but
      careful comparison of the relevant gastroenterological and rheumatological
      literatures suggests several common areas that are worthy of greater attention
      than they are currently receiving. These could include studies to address the
      following questions: (1) What are the functional and antigen-binding differences
      of the HLA class II alleles that are differently associated with rheumatoid
      arthritis and ulcerative colitis? (2) Why are both Crohn's disease and rheumatoid
      arthritis associated with smoking, yet, with one condition (Crohn's disease)
      increasing recently in incidence and the other (rheumatoid arthritis) becoming
      less common? (3) Which genetic and/or environmental factors distinguish the
      Turkish patients with HLA-B51-associated Behcet's disease who tend not to develop
      colitis and the Japanese patients with HLA-B51-associated Behcet's disease who
      develop colitis? (4) Is pANCA directly involved in the pathogenesis of ulcerative
      colitis-given evidence of its direct involvement in the pathogenesis of
      vasculitis? (5) Given the arguably greater similarity between rheumatoid
      arthritis and ulcerative colitis than with Crohn's disease, is etanercept
      effective in ulcerative colitis? (6) Do the very different risks of cancer in
      chronically inflamed colon and inflamed joints imply that cancer development
      requires both NFkappaB activation, to inhibit apoptosis, and the presence of
      agents, such as bacteria, to initiate DNA damage?

PMID- 16280269
TI  - Association of estrogen receptor beta gene polymorphisms with left ventricular
      mass and wall thickness in women.
AB  - BACKGROUND: Left ventricular (LV) hypertrophy is a significant risk factor for
      cardiovascular disease. Given sex-based differences in cardiac structure and
      remodeling, we hypothesized that variation in estrogen pathway genes might be
      associated with alteration of LV structure. METHODS: We studied 1249 unrelated
      individuals, 547 men and 702 women (mean age 59 years) from the Framingham Heart
      Study. Eight single nucleotide polymorphisms in the genes for estrogen receptor
      alpha and estrogen receptor beta (ESR2) were tested for association with 5 LV
      measures: LV mass (LVM), LV wall thickness (LVWT), LV internal diameter at end
      diastole and end-systole, and fractional shortening. Sex-specific multiple
      regression analyses were performed adjusting for age, weight, height, systolic
      and diastolic blood pressure, hypertension treatment, diabetes, and in women,
      menopausal status. RESULTS: In men, there was no evidence of association between
      the estrogen pathway polymorphisms tested and LV structure or function. In women,
      however, two polymorphisms, ESR2 rs1256031 and ESR2 rs1256059, in linkage
      disequilibrium with one another, were associated with LVM and LVWT (P = .0007 to
      .03); the association was most pronounced in those women with hypertension (P =
      .0006 to .01). The association did not appear to be explained by variation in
      blood pressure, plasma lipoprotein levels, or hyperglycemia. CONCLUSIONS: The
      ESR2 polymorphisms are associated with LV structural differences in women with
      hypertension in a community-based population. These data are consistent with the
      hypothesis that genetic factors may mediate part of the observed sex-based
      differences in LV structure and remodeling.

PMID- 16280270
TI  - Hypertension in HIV-infected patients: prevalence and related factors.
AB  - BACKGROUND: Little is known about hypertension in the HIV-infected population.
      This study aimed to assess the prevalence of hypertension and related factors in
      HIV-infected patients. METHODS: In this prospective cross-sectional study, 710
      HIV-infected patients (626 on combination antiretroviral therapy and 84 naive)
      managed at the outpatient clinic of a tertiary hospital during 2003 and 802
      controls completed the study protocol consisting of medical examination and a 6
      month follow-up period including three control visits. RESULTS: Hypertension
      prevalence was 13.1% in HIV-infected patients and 13.5% in the control group. Age
      (per 10-year increment) (odds ratio [OR]: 1.92; 95% confidence interval [CI]:
      1.48-2.48), body mass index (OR: 1.18; 95% CI: 1.10-1.27), and lipoaccumulation
      pattern of fat redistribution (OR: 2.26; 95% CI: 1.20-4.24) were independently
      and significantly associated with the presence of hypertension in HIV-infected
      patients at logistic regression analysis. CONCLUSIONS: The present results
      suggest no meaningful difference in prevalence of hypertension between subjects
      with and without HIV infection. Thus, the influence of combination antiretroviral
      therapy appears to have little impact on the prevalence of hypertension.

PMID- 16280271
TI  - Dipping and variability of blood pressure and heart rate at night are heritable
      traits.
AB  - BACKGROUND: Blunted nocturnal blood pressure dipping (NBPD) as well as high
      variability in blood pressure (BPV) and low variability in heart rate (HRV), are
      associated with increased cardiovascular morbidity and mortality. The aim of this
      study was to determine whether these traits are heritable. METHODS: We studied
      260 healthy siblings without antihypertensive drugs from 118 Swedish families.
      The BPV and HRV were defined as the standard deviation of BP and heart rate
      values recorded during 24 h, daytime (6 am to 10 pm), and night-time (10 pm to 6
      am). The NBPD was defined as the ratio between night-time and daytime BP.
      Heritability was estimated with a maximal likelihood method implemented in the
      Solar software package with and without adjustment for significant covariates.
      RESULTS: At night, significant heritability was found for systolic (33%, P <
      .05), diastolic (36%, P < .05), and mean (42%, P < .01) BPV. After covariate
      adjustment the corresponding heritability values were 23% (P = .08), 29% (P <
      .05), and 37% (P < .05). Daytime BPV was not heritable. The heritability of NBPD
      was 38% (P < .05) for systolic, 9% (P = .29) for diastolic, and 36% (P < .05) for
      mean BP, but after adjustment only systolic NBPD was significant (29%, P < .05).
      Heart rate was highly heritable both during daytime (57%, P < .001) and night
      time (58%, P < .001), but the variability of heart rate, after adjustment, was
      only significant at night (37%, P < .05). CONCLUSIONS: Our data suggest that BPV
      and HRV are partially under genetic control and that genetic loci of importance
      for these traits could be mapped by linkage analysis.

PMID- 16280272
TI  - Long-term reproducibility of routine ambulatory blood pressure monitoring in
      stable pediatric renal transplant recipients.
AB  - BACKGROUND: The aim of this study was to evaluate, in stable pediatric renal
      transplant recipients, the long-term reproducibility of average office and
      ambulatory blood pressure (BP) readings and day-to-night BP variability under
      similar clinical conditions. METHODS: The study involved 18 pediatric kidney
      transplant recipients who had repeated routine office and 24-h ambulatory BP
      monitoring (ABPM) in three visits, 12 months apart, over a 2-year period.
      Reproducibility of office and ambulatory BP averages between pairwise
      measurements were analyzed by calculating the mean difference and the standard
      deviation of the difference (SDD). Nondippers were arbitrarily defined by
      applying both a pediatric and an adult definition, respectively. RESULTS:
      Throughout the 2-year period, there were no significant differences in mean
      office, 24-h, daytime, night-time systolic, and diastolic BP values. Overall, SDD
      were lower for ambulatory BP recordings than for office BP measurements
      indicating a better long-term reproducibility for ABPM compared with office BP
      readings. The SDD for systolic and diastolic BP ranged from 12.4 to 13.7 and 6.3
      to 9.5 for office BP and from 6.2 to 7.3 and 5.1 to 5.6 for 24-h BP,
      respectively. Regardless of the definition applied to define dipper and nondipper
      status, only half of the study group showed consistency in their circadian BP
      variability when comparing the three ABPMs. CONCLUSIONS: The present study
      demonstrates that long-term reproducibility of ABPM is superior to that for
      office measurements. Day-to-night BP variability, however, appears to change over
      time, making it questionable to classify a recipient as a dipper or nondipper
      during a single ABPM recording.

PMID- 16280273
TI  - Self-monitoring of blood pressure promotes achievement of blood pressure target
      in primary health care.
AB  - BACKGROUND: The majority of hypertensive patients do not reach the target blood
      pressure (BP). We sought to clarify whether intermittent self-monitoring of BP
      leads to better BP control compared to ordinary treatment in general practice.
      METHODS: Two hundred sixty-nine hypertensive patients participated in this
      multicenter, randomized, parallel-group study in primary health care. Home BP was
      measured in the self-monitoring (SM) group at 0, 2, 4, and 6 months, and in the
      control (C) group at 0 and 6 months. The participating physicians were instructed
      to intensify the antihypertensive therapy when needed. RESULTS: At the beginning,
      both groups had similar home BP levels (SM 143.1 +/- 17.4/85.3 +/- 7.4 mm Hg v C
      143.9 +/- 18.3/85.4 +/- 7.5 mm Hg). After 6 months, there were significant
      decreases in systolic (P <or= .0001), diastolic (P <or= .0029), and pulse
      pressures (P <or= .021) in both groups. Systolic (-7.8 +/- 13.1 mm Hg v -4.5 +/-
      12.2 mm Hg, P = .047) and pulse pressure (-4.7 +/- 9.0 mm Hg v -2.2 +/- 10.0 mm
      Hg, P = .042) decreased significantly more than in the self-monitoring group. The
      decrease in diastolic pressure was similar in both groups (SM -3.1 +/- 6.2 mm Hg
      v C -2.3 +/- 8.3 mm Hg, P = not significant). The patients in the SM group
      reached home BP target more often than those in the C group (29% v 16%, P =
      .016). There was a nonsignificant trend toward lower office BP values in the SM
      group. CONCLUSIONS: Self-monitoring decreased systolic and pulse pressure
      significantly more than ordinary treatment and promoted achievement of target BP.
      This was most likely due to improved patient compliance and more active treatment
      by the physicians. Our results suggest that home measurement is useful in the
      control of hypertension.

PMID- 16280274
TI  - Self-monitoring of blood pressure in primary care: is it useful?

PMID- 16280275
TI  - Cardiovascular outcome in treated hypertensive patients with responder, masked,
      false resistant, and true resistant hypertension.
AB  - BACKGROUND: The aim of this study was to evaluate the cardiovascular outcome in
      apparently responder hypertensive patients with responder and masked
      hypertension, and in apparently resistant hypertensive patients with false and
      true resistant hypertension. METHODS: The occurrence of fatal and nonfatal
      cardiovascular events was evaluated in 340 patients with responder hypertension
      (clinic blood pressure [BP] <140/90 mm Hg and daytime BP <135/85 mm Hg), 126 with
      masked hypertension (clinic BP <140/90 mm Hg and daytime BP >135 or 85 mm Hg),
      146 with false resistant hypertension (clinic BP >or=140 or 90 mm Hg and daytime
      BP <135/85 mm Hg), and 130 with true resistant hypertension (clinic BP >or=140 or
      90 mm Hg and daytime BP >135 or 85 mm Hg). RESULTS: During follow-up period (4.98
      +/- 2.9 years), the event-rate per 100 patient-years was 0.87, 2.42, 1.2, and 4.1
      in patients with responder, masked, false resistant, and true resistant
      hypertension, respectively. After adjustment for several covariates, including
      clinic BP (forced into the model), Cox regression analysis showed that
      cardiovascular risk was significantly higher in masked hypertension (masked
      versus responder hypertension, relative risk [RR] 2.28, 95% confidence interval
      [CI] 1.1-4.7, P < .05) and in true resistant hypertension (true resistant versus
      responder hypertension, RR 2.94, 95% CI 1.02-8.41, P < .05), whereas there was no
      significant difference between false resistant and responder hypertension.
      CONCLUSIONS: This study shows that patients with masked hypertension are at
      higher risk than those with responder hypertension, and that those with false
      resistant hypertension are at lower risk than those with true resistant
      hypertension. Ambulatory BP monitoring should be performed in treated
      hypertensive patients to obtain a better prognostic stratification.

PMID- 16280276
TI  - Reflections on masked hypertension.

PMID- 16280277
TI  - Aortic valve sclerosis and albuminuria predict cardiovascular events
      independently in hypertension: a losartan intervention for endpoint-reduction in
      hypertension (LIFE) substudy.
AB  - BACKGROUND: Aortic valve (AV) sclerosis and urine albumin/creatinine ratio (UACR)
      are both markers of atherosclerosis. We aimed to investigate whether they
      predicted cardiovascular (CV) events independently in patients with hypertension
      and electrocardiographic left ventricular (LV) hypertrophy. METHODS: After 2
      weeks of placebo treatment, clinical, laboratory, and echocardiographic variables
      were assessed in 960 hypertensive patients from the LIFE Echo substudy who had
      electrocardiographic LV hypertrophy. Morning urine albumin and creatinine were
      measured calculating UACR. The presence of AV sclerosis was defined as valve
      thickening or calcification. Fifteen patients with mild AV stenosis were
      excluded. The patients were followed for 60 +/- 4 months and the composite
      endpoint (CEP) of CV death, nonfatal stroke, or nonfatal myocardial infarction
      was recorded. RESULTS: A value of UACR above the median value of 1.406 was
      associated with higher incidence of CEP and CV death in patients with AV
      sclerosis (CEP: 18.8% v 9.0% P < 0.05, CV death: 7.1% v 0.7% P < 0.01) and in
      patients without AV sclerosis (CEP: 14.0% v 4.9% P < 0.001, CV death: 5.1% v 1.1%
      P < 0.01). In Cox regression analysis, AV sclerosis predicted CEP (hazard ratio
      [HR] = 1.52, P < .05), but not CV death (HR = 1.30 [0.62 to 2.70], NS)
      independently of logUACR (HR = 1.70 and HR = 3.25, both P < .001). After
      adjusting for the Framingham Risk Score, CV disease, diabetes, smoking, and
      treatment allocation, AV sclerosis predicted CEP (HR = 1.5, P < .05) but not CV
      death (HR = 1.4, NS) independently of logUACR (HR = 1.2, P = .09 and HR = 1.94, P
      < .05). CONCLUSIONS: In hypertensive patients with electrocardiographic LV
      hypertrophy, AV sclerosis predicted CEP but not CV death independently of UACR
      after adjusting for CV risk factors and treatment allocation, indicating that AV
      sclerosis and UACR might be markers of different aspects of the atherosclerotic
      process.

PMID- 16280278
TI  - G-6A polymorphism of the angiotensinogen gene and its association with left
      ventricular mass in asymptomatic young adults from a biethnic community: the
      Bogalusa Heart Study.
AB  - BACKGROUND: Angiotensinogen (AGT), the precursor of angiotensin II and a rate
      limiting factor in the renin-angiotensin system, is implicated in left
      ventricular hypertrophy, as angiotensin II is a potent stimulator of cardiac
      growth. A genetic variant (G-6A) in the proximal promoter region of the AGT gene
      may be particularly important for changes in left ventricular mass (LVM).
      However, previous findings associating this variant with LVM among relatively
      older adults with cardiovascular morbidity are inconsistent and contradictory.
      METHODS: This study examined the effect of G-6A polymorphism on LVM in a biethnic
      (African American and white), community-based sample of 362 asymptomatic younger
      adults (mean age 32.5 years, 71% white, 39% male). Two-dimensional M-mode
      echocardiography was used to assess LVM, and the indexation of LVM for
      height(2.7) (LVMI) was used to adjust for body size. RESULTS: The frequency of
      the variant A(-6) allele was higher in subjects of African American than in white
      ethnicity (0.819 v 0.439, P < .0001), with carriers (GA+AA) representing 97.0% of
      African American as compared to 66.6% of white subjects. After adjusting for age,
      ethnicity (for total sample), gender, body mass index, systolic BP, and
      homeostasis model assessment index of insulin resistance, mean levels for both
      LVM and LVMI showed a significant decreasing trend with increasing gene dosage of
      the A(-6) allele in white subjects, African American subjects, and the total
      sample. CONCLUSIONS: These results indicate that the A(-6) allele frequency
      differs markedly between African Americans and white individuals, and that the
      variant allele modulates LVM and LVMI in a beneficial manner in asymptomatic
      young adults of white and African American ethnicities.

PMID- 16280279
TI  - Methylenetetrahydrofolate reductase gene polymorphisms in essential hypertension
      relation: with the development of hypertensive end-stage renal disease.
AB  - BACKGROUND: The pathogenesis of hypertensive nephropathy is multifactoral and in
      addition to BP, other factors contribute to the development of this renal
      pathology and its progression to end-stage renal disease. These include genetic
      predisposition and increased pleasure level of homocysteine-intermediate protein
      catabolism product known to induce kidney injury. The 677C --> T polymorphism in
      the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene is associated with
      elevated homocysteine level in the general population, and therefore it has been
      hypothesized to be a risk factor for the development of renal failure in the
      course of essential hypertension. METHODS: In this case-control, cross-sectional
      study the frequency of the MTHFR 677C --> T and the 1298A --> C polymorphism was
      compared between patients with hypertension-related chronic renal failure (n =
      90), patients with essential hypertension without kidney injury (n = 90), and
      healthy individuals (n = 90) who were matched for age and gender. In addition,
      the influence of these polymorphisms on homocysteine concentration in individuals
      with essential hypertension was examined. RESULTS: The frequency of the MTHFR 677
      TT genotype did not differ between groups (4.5%, 12.3%, and 11.1%, respectively).
      Patients with hypertension and the 677TT genotype showed significantly higher
      homocysteine levels as compared to individuals having CC and CT. In the
      multivariate correlation analysis the MTHFR 677TT genotype (P < .01; beta =
      0.27), age (P < .001; beta = 0.33), and body mass index (P < .01; beta = 0.3)
      were independent predictors for total homocysteine level. CONCLUSIONS: Plasma
      homocysteine levels in individuals with essential hypertension is affected by the
      MTHFR 677C --> T polymorphism. However, we did not prove the hypothesis that
      MTHFR 677C --> T influences the risk of development of renal failure in the
      course of hypertension.

PMID- 16280280
TI  - Hypertension induced by aortic coarctation above the renal arteries is associated
      with immune cell infiltration of the kidneys.
AB  - BACKGROUND: Renal tubulointerstitial infiltration of activated T cells and
      macrophages is invariably present and plays a role in elevation of arterial
      pressure in nearly all animal models of hypertension (HTN). The role, if any, of
      elevated renal arterial pressure in the pathogenesis of this inflammatory process
      is uncertain. Also unclear is whether the cellular infiltration is caused by the
      local activation of immune cells in the kidney or a consequence of leukocyte
      activation in the systemic circulation. METHODS: We studied activation of
      peripheral blood leukocytes and cellular infiltration in the kidneys of Sprague
      Dawley rats with abdominal aorta coarctation (banding) above renal arteries,
      which causes severe HTN proximal but not distal to coarctation. RESULTS: Compared
      with the sham operated controls, the aorta-banded group exhibited
      tubulointerstitial accumulation of activated T cells, macrophages, angiotensin-II
      positive cells, leukocyte function-associated antigen-1 integrin expressing
      cells, increased nitrotyrosine abundance (a measure of oxidative stress), and
      increased macrophage chemoattractant protein-1 in the kidneys which are not
      exposed to HTN in this model. These findings were associated with the activation
      of the circulating leukocytes in the aorta-banded animals. CONCLUSIONS: Increased
      baromechanical stress is not a requisite for accumulation of T cells and
      macrophages in the kidney in the coarctation-induced HTN and possibly in other
      hypertensive disorders. On the contrary, renal hypoperfusion and the consequent
      activation of renin-angiotensin system may mediate this process by promoting
      local induction of chemoattractant and inflammatory cytokines. The observed
      tubulointerstitial inflammation in this model is associated with leukocyte
      activation in the systemic circulation.

PMID- 16280281
TI  - High pulse pressure associated with cardiovascular events in patients with type 2
      diabetes undergoing hemodialysis.
AB  - BACKGROUND: The aims of this study were to examine systolic BP (SBP), diastolic
      BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) in patients with
      type 2 diabetes undergoing hemodialysis (HD), and to assess the relationships
      between these parameters and cardiovascular (CV) events such as coronary heart
      disease and congestive cardiac failure. METHODS: A total of 80 Afro-Caribbean
      type 2 diabetic patients undergoing hemodialysis in three centers in Guadeloupe,
      French West Indies, were included in this cross-sectional study. Pre- and
      postdialysis BP were recorded. Logistic regression methods and areas under the
      receiver operating characteristic curves were used. RESULTS: The mean age (+/-
      standard deviation) was 62.2 years (+/-10.2 years). A total of 24 subjects (30%)
      had one or more CV events. Sixteen (20%) had coronary disease, 15 (18.8%) cardiac
      failure, and seven (8.8%) had both. The medians [interquartile ranges] for
      predialysis PP was higher in patients with CV comorbidity than in patients
      without a history of CV at 84.5 mm Hg [74.5 to 92.3]v 69.5 mm Hg [61.0 to 79.5],
      P = .003. Areas under the ROC curves (95% confidence intervals) predialysis were
      significant only for SBP and PP at 0.70 (0.58 to 0.82) v 0.71 (0.59 to 0.83)
      without statistical differences. After adjustment for gender, age, body mass
      index, antihypertensive use, time on hemodialysis (>or=2 years), and hemoglobin
      rate, the odds ratio was significant only predialysis, and a higher odds ratio
      was found for PP at 2.25 (1.22 to 4.18), P = .01, than for SBP 1.97 (1.12 to
      3.49), P = .02. CONCLUSIONS: Our results suggest that the strongest association
      of PP with CV morbidities should be considered in therapeutic strategies. These
      results show the necessity of targeting antihypertensive treatment to patients'
      predialysis blood pressure values.

PMID- 16280282
TI  - Pulse pressure predicts cardiovascular risk in patients with type 2 diabetes
      mellitus.
AB  - BACKGROUND: Pulse pressure (PP), a marker of arterial stiffness, is a better
      predictor of coronary heart disease (CHD) risk than systolic blood pressure (SBP)
      or diastolic blood pressure (DBP) in older adults. Whether this is also true in
      subjects with type 2 diabetes, who are at increased risk for cardiovascular
      disease, is unknown. METHODS: Data on 2911 type 2 diabetic subjects relating to
      blood pressure (BP), other risk factors, and cardiovascular events were
      abstracted from The Cardiff Diabetes Database. Logistic regression was used to
      assess the relationship among BP components and the risk of CHD, cerebrovascular
      (CVD), and peripheral vascular (PVD) events after correction for age, gender,
      cholesterol, and smoking status. RESULTS: In the 4-year follow-up period there
      were 574 CHD, 168 CVD, and 157 PVD events. Both PP and SBP, but not DBP, were
      positively associated with the risk of all event types. However, PP emerged as
      the best predictor of CHD events, and SBP as the best predictor of CVD and PVD
      events. Total and HDL-cholesterol were the most important variables associated
      with PP after age. CONCLUSIONS: In summary, PP is a better predictor of CHD
      events than SBP in persons with type 2 diabetes, but the converse is true for CVD
      and PVD.

PMID- 16280284
TI  - Blockade of sympathetic nervous system activity by rilmenidine increases plasma
      adiponectin concentration in patients with essential hypertension.
AB  - BACKGROUND: Adiponectin is an adipose tissue-specific protein with
      antiatherogenic and insulin-sensitizing properties. In patients with essential
      hypertension plasma adiponectin levels are lower than in healthy subjects. It is
      hypothetized that low plasma adiponectin concentration may be involved in the
      pathogenesis of vascular complications in hypertension. The aim of the study was
      to evaluate the effect of 6 months of antihypertensive therapy with rilmenidine
      on plasma adiponectin concentration in patients with essential hypertension.
      METHODS: In 20 patients with essential hypertension (mean age 39 +/- 14 years; 11
      F, 9 M; mean duration of hypertension 8 +/- 9 years) plasma adiponectin
      concentration (ELISA; B-Bridge International, San Jose, CA), insulin sensitivity
      (metabolic clearance of glucose-M value and M/plasma insulin ratio) by the
      euglycemic-hyperinsulinemic glucose clamp technique, and body fat content (DEXA)
      were estimated twice, before and after 6 months of antihypertensive monotherapy
      with rilmenidine (daily dose 1 to 2 mg). RESULTS: The 6 months of treatment with
      rilmenidine resulted in a significant decrease of systolic (P = .007), diastolic
      (P = .002), and mean arterial blood pressure (P = .002), no significant change of
      body mass index (27.7 +/- 4.7 and 27.6 +/- 4.4 kg/m(2)), total body fat content
      (25.4 +/- 7.3 and 24.9 +/- 6.8 kg), and insulin sensitivity parameters (M value
      6.0 +/- 2.5 and 5.8 +/- 4.3 mg/kg/min and M/plasma insulin ratio 7.4 +/- 5.0 and
      6.9 +/- 4.3 mg/kg/min/mU/L). However after 6 months of treatment with rilmenidine
      a significant increase in plasma adiponectin concentration (from 12.5 +/- 6.1 to
      16.9 +/- 11.1; P = .0002) was observed. CONCLUSIONS: Antihypertensive therapy
      with rilmenidine correlates with an increase of plasma adiponectin concentration
      without any significant changes of insulin sensitivity and body fat content in
      patients with essential hypertension.

PMID- 16280285
TI  - Differential associations of statin and fibrate treatment with carotid arterial
      remodeling.
AB  - BACKGROUND: The effects of statins on intima-media thickness (IMT) are well
      documented, whereas those of fibrates are unknown. Therefore we compared IMT
      under treatment with each class of drugs. METHODS: We studied a cohort of
      consecutive dyslipidemic subjects treated with statin (n = 291) or fibrate (n =
      82) drugs. Fibrate-treated subjects were matched with the same number of statin
      treated subjects to obtain two subgroups of similar demographic and risk factors
      including LDL cholesterol. Common carotid far wall IMT and lumen diameter were
      measured by ultrasonography. RESULTS: In the entire study population, IMT was
      greater in the fibrate group than in the statin group (P < .001), even after
      adjustment for LDL cholesterol and other covariates (P < .05). In the matched
      groups, IMT was greater in fibrate group than in the statin group (P < .01), even
      after adjustment for LDL cholesterol and other covariates including treatment
      duration (P < .01). The IMT correlated positively with treatment duration in the
      fibrate group (P < 0.05) but not in the statin group. In addition, IMT correlated
      positively with carotid lumen diameter in both the fibrate and statin groups (P <
      .05, P < .01) but with a lower slope in the former (P < .05). CONCLUSIONS: In
      this study fibrate treatment was associated with greater IMT, steeper IMT-time
      relationship, and lower compensatory carotid enlargement than was statin
      treatment. These differences were not explained by differences in LDL
      cholesterol.

PMID- 16280286
TI  - A home blood pressure monitoring study comparing the antihypertensive efficacy of
      two angiotensin II receptor antagonist fixed combinations.
AB  - BACKGROUND: The objective of this prospective, randomized, open-label, blinded
      endpoint study was to compare the antihypertensive efficacy of valsartan 80 mg v
      irbesartan 150 mg when combined with hydrochlorothiazide (HCTZ) 12.5 mg. METHODS:
      Untreated or uncontrolled hypertensive adults (n = 800) were enrolled by primary
      care physicians. After a 5-week open-label lead-in phase in which all patients
      received 12.5 mg HCTZ once daily, subjects whose blood pressure (BP) remained
      uncontrolled were randomized (n = 464) to valsartan/HCTZ (80/12.5 mg) or
      irbesartan/HCTZ (150/12.5 mg) for 8 weeks. Home BP monitoring (HBPM) was
      performed in the morning and in the evening for 5 days, at baseline, and after 8
      weeks. Office BP measurements were obtained at baseline and after 8 weeks.
      RESULTS: Irbesartan/HCTZ produced greater reductions in average systolic BP (SBP)
      and diastolic BP (DBP) measured by HBPM than valsartan/HCTZ (SBP: -13.0 v -10.6
      mm Hg, P = .0094; DBP: -9.5 v -7.4 mm Hg, P = .0007). These differences were more
      pronounced in the morning (trough) than in the evening. Office BP measurements
      also showed greater reductions in trough seated SBP and DBP with irbesartan/HCTZ
      compared with valsartan/HCTZ. Normalization rates observed with HBPM (SBP <135 mm
      Hg and DBP <85 mm Hg) were significantly greater with irbesartan/HCTZ than with
      valsartan/HCTZ (50.2 v 33.2%; P = .0003). The overall safety was similar in the
      two groups. CONCLUSIONS: The superior BP-lowering potency of the fixed
      combination irbesartan/HCTZ (150/12.5 mg) over valsartan/HCTZ (80/12.5 mg),
      evidenced independently from the investigators by HBPM, supports the use of this
      technique in trials with prospective, randomized, open-label, blinded-endpoint
      designs.

PMID- 16280287
TI  - Nocturnal hypoxia is associated with silent cerebrovascular disease in a high
      risk Japanese community-dwelling population.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) is recognized as a risk factor for
      cerebrovascular disease. The objective of this study was to investigate the
      relationship between nocturnal hypoxia and silent cerebral infarct (SCI) in the
      general population. METHODS: In the 2001 annual health check in Nishiarita,
      Japan, 170 individuals at high risk were screened who met more than three of the
      following criteria: high blood pressure, hypercholesterolemia, left ventricular
      hypertrophy by electrocardiography, hemoglobinA(1)c >6.5%, proteinuria, central
      obesity, heavy smoking habit, heavy drinking, and family history of stroke.
      Overnight pulse oximetry, brain magnetic resonance imaging, and carotid/cardiac
      ultrasonography were performed in 146 (mean age 67.4 +/- 9.0 years) of the 170
      individuals in whom pulse oximetry was successfully performed. RESULTS: Subjects
      were classified into a nocturnal hypoxia group (n = 36) and a nonhypoxia group (n
      = 110) based on a 3% oxygen desaturation index (ODI) 5.6 times per hour during
      sleep (highest quartile) by pulse oximetry. The presence of silent cerebral
      infarct (SCI) (57% v 35%, P = .03) was significantly higher in the hypoxia group
      than in the nonhypoxia group. The number of SCI was positively correlated with
      age (r = 0.23, P < .01), systolic blood pressure (r = 0.196, P < .05), and 3% ODI
      (r = 0.318, P < .001). Even after adjustment for confounding factors using
      logistic regression analysis, nocturnal hypoxia (odds ratio = 2.2, 95% confidence
      interval = 1.10 to 5.30, P = .026) as well as systolic blood pressure and age (10
      year increase: odds ratio = 1.22, 95% confidence interval 1.00 to 1.48, P = .048)
      were independently associated with SCI in the study subjects. CONCLUSIONS: Based
      on the study results, SDB assessed by overnight pulse oximetry was associated
      with silent cerebral disease in a high-risk, community-dwelling Japanese
      population.

PMID- 16280288
TI  - Simvastatin and losartan enhance nitric oxide and reduce oxidative stress in salt
      induced hypertension.
AB  - BACKGROUND: The renin-angiotensin-aldosterone system and oxidative stress play a
      major role in the pathogenesis of hypertension. METHODS: We examined the effects
      of simvastatin, an HMG-CoA inhibitor, and losartan, an angiotensin type 1
      receptor antagonist, in Dahl rats fed a high salt diet (8% NaCl), and treated
      with either simvastatin (3 mg/kg/d), losartan (10 mg/kg/d), or their combination
      using the drinking water as vehicle, for 3 weeks. Mean blood pressure (MAP) was
      measured by tail-cuff plethysmography. Plasma levels of nitric oxide (NO) and
      prostanoids, as well as plasma and tissue angiotensin II (Ang II) and aldosterone
      (ALDO) were analyzed by enzyme immunoassay. Renal and aortic superoxide
      production was determined by fluorescence spectrometry. Vascular reactivity of
      second-order mesenteric arteries was assessed in vitro. RESULTS: Simvastatin,
      losartan, and the drug combination attenuated the salt-induced increase in MAP.
      Plasma NO was elevated by simvastatin, losartan, and the combination, whereas
      plasma thromboxane was reduced by losartan. Simvastatin, losartan, and the
      combination reduced renal Ang II, but only the combination reduced cardiac Ang
      II. Heart and renal ALDO were reduced by simvastatin, losartan, and the
      combination. Aortic and renal NADPH-dependent superoxide production was reduced
      by simvastatin, losartan, and the combination. The response to acetylcholine, in
      mesenteric arteries preconstricted with norepinephrine, was greater in the
      losartan group. CONCLUSIONS: Thus, treatment with simvastatin and losartan
      lowered oxidative stress and improved endothelial function. Simvastatin
      significantly reduced the effect of losartan on vascular reactivity in mesenteric
      arteries, suggesting that their combination may be contraindicated.

PMID- 16280289
TI  - Increased transient receptor potential channel TRPC3 expression in spontaneously
      hypertensive rats.
AB  - BACKGROUND: Disturbances in the regulation of cytosolic calcium concentration
      have been attributed to primary hypertension, but the role of calcium-permeable
      transient receptor potential canonical channel 3 (TRPC3) has not yet been
      evaluated in primary hypertension. METHODS: Expression of TRPC3 was determined
      using in-cell Western assay. Evaluation of RNA interference for the
      downregulation of a specific gene in cells by small interfering RNA was
      performed. Measurements of cytosolic calcium were carried out using the
      fluorescent dye fura2. RESULTS: Expression of TRPC3 was significantly increased
      in monocytes from spontaneously hypertensive rats (SHR) compared with
      normotensive Wistar-Kyoto rats (WKY). Transplasmamembrane calcium influx and
      thapsigargin-induced sustained calcium increase were significantly higher in SHR
      compared with WKY. In the presence of the TRP channel blocker SKF-96365 these
      differences were no longer observed. Specific TRPC3-knockdown by transfection of
      monocytes from SHR with small interfering RNA significantly reduced TRPC3
      expression, trans-plasma membrane calcium influx, and thapsigargin-induced
      sustained calcium increase. CONCLUSIONS: This study shows, for the first time,
      increased TRPC3 channel expression and increased TRPC3-related calcium influx in
      SHR.

PMID- 16280290
TI  - Rebound weight gain as associated with high plasma norepinephrine levels that are
      mediated through polymorphisms in the beta2-adrenoceptor.
AB  - BACKGROUND: A successful weight loss program is essential treatment for obesity
      related diseases, but it is well known that the majority of individuals do not
      succeed in weight loss maintenance. The present study evaluates hormonal
      mechanisms and the relationship of beta2-adrenoceptor polymorphisms involved in
      individuals who regain weight after initially successful weight loss. METHODS:
      Overweight Japanese men (n = 154) were enrolled in a 24-month weight loss
      program. Body mass index (BMI), total body fat mass, plasma norepinephrine (NE)
      and leptin levels, and beta2-adrenoceptor polymorphisms (Arg16Gly, Gln27Glu) were
      measured every 6 months for the 24-month period. Maintenance of weight loss was
      defined as significant weight loss (>or=10% reduction) from entry weight at 6
      months and maintenance of the weight loss for an additional 18 months. Rebound
      weight gain was defined as significant weight loss at 6 months but subsequent
      regain of body weight during the next 18 months. RESULTS: The results showed that
      37 subjects maintained weight loss during 24 months, whereas 36 subjects had
      rebound weight gain. The BMI at entry and calorie intake and physical activity at
      each period were similar between the two groups. Subjects who maintained weight
      loss had at entry a significantly lower fat mass and plasma NE levels compared to
      those with rebound weight gain. Body fat mass, NE, and leptin levels at entry
      predicted the degree of change in body weight during the 24-month study period.
      Subjects with rebound weight gain had a significantly higher frequency of the
      Gly16 allele for the beta2-adrenoceptor polymorphism compared to subjects who had
      a 24-month maintenance of weight loss. Subjects carrying the Gly16 allele also
      had significantly higher plasma NE, leptin, and body fat mass levels and a
      greater waist-to-hip ratio both at entry and throughout the study. CONCLUSIONS: A
      high initial degree of body fat mass and high plasma NE levels as determined by
      the Gly16 allele for the beta2-adrenoceptor polymorphisms predict those
      individuals who will have rebound weight gain after their initial successful
      weight loss.

PMID- 16280291
TI  - Sympathetic drive as a determinant of weight loss intervention outcome strengths
      and limitations.

PMID- 16280292
TI  - Occupational contact urticaria and protein contact dermatitis.
AB  - Irritant dermatitis and eczema are the most prevalent occupational skin diseases.
      Less common are immediate contact reactions such as contact urticaria and protein
      contact dermatitis. Occupational contact urticaria can be subdivided into two
      categories, immunological and non immunological. However, some agents can induce
      these two types of reactions. Contact urticaria to natural rubber latex is
      particularly frequent among health care personnel, but contact urticaria to a
      wide variety of other substances occurs in many other occupations. Among those at
      risk are cooks, bakers, butchers, restaurant personnel, veterinarians,
      hairdressers, florists, gardeners, and forestry workers. Protein contact
      dermatitis in some of these occupations is caused principally by proteins of
      animal or plant origin, especially among individuals with a history of atopic
      dermatitis. Diagnosis requires careful interrogation, clinical examination and
      skin tests (open tests and prick tests with immediate lecture) to identify a
      particular contact allergen.

PMID- 16280294
TI  - Bathing-suit ichthyosis. A peculiar phenotype of lamellar ichthyosis in South
      African blacks.
AB  - Autosomal recessive congenital ichthyosis is a heterogeneous group of disorders
      of cornification showing a wide spectrum of clinical phenotypes.Here, thirteen
      cases of a so far unreported distinct type of autosomal recessive congenital
      ichthyosis are described. All the skin lesions were present at birth and ten were
      then compatible with collodion baby. Shedding of the collodion led to an
      ichthyotic condition with a very characteristic distribution of the lesions which
      involved the trunk, the most proximal parts of the upper limbs, scalp and neck
      but spared the central face and extremities. The term "bathing-suit" ichthyosis
      is suggested for this unusual phenotype of lamellar ichthyosis.

PMID- 16280293
TI  - The skin in primary immunodeficiency disorders.
AB  - Primary immunodeficiency disorders comprise serious and rare diseases,
      predominantly in children. The skin may be involved in a primary immunodeficiency
      and the cutaneous alterations such as infections, eczematous dermatitis,
      erythroderma, autoimmune dermatoses and vasculitis may be the basis for the
      ultimate diagnosis. Dermatologists may realize something is wrong with the
      immunity of their patient and prompt diagnosis of the defect can lead to
      lifesaving treatment. Since atypical presentations of well known dermatoses are
      common in immunodeficiency disorders, histopathology and bacterial, fungal or
      viral tests of the skin lesions are often indispensable. The knowledge of skin
      findings in primary immunodeficiency diseases may help dermatologists to play a
      role in the early detection of these diseases. Key findings constitute specific
      skin symptoms combined with unusual or severe infections.

PMID- 16280295
TI  - Further delineation of the hypotrichosis-deafness syndrome.
AB  - We recently delineated a novel disorder characterized by hypotrichosis, nail
      dystrophy and sensorineural deafness and caused by a missense mutation in GJB2
      (connexin26). The patient, a girl, was two years old when we first saw her. We
      had the opportunity to re-examine her at four years of age and found that the
      phenotype had changed appreciably. The hypotrichosis was less pronounced, but the
      nail dystrophy had worsened. Intriguingly, the phenotype now included a mucositis
      and skin lesions identical to those found in erythrokeratodermia variabilis.
      There is now a considerable overlap with other gap junction disorders and we
      propose that some cases of erythrokeratodermia variabilis without mutations in
      either GJB3 or GJB4 but with deafness may be caused by mutations in GJB2. This is
      the first description of the evolution of a gap junction disease over time and we
      note that follow-up of patients suffering from gap junction skin disorders is
      necessary to fully delineate the phenotypes caused by mutations in gap junction
      genes.

PMID- 16280296
TI  - Delineation of the various shapes and patterns of nevi.
AB  - It has been proposed that all nevi reflect mosaicism, and this concept has been
      corroborated at the molecular level in a number of nevi. If the concept of
      mosaicism holds true, one would expect that the various types of nevi should be
      characterized by intrinsic shapes or patterns. A photographic review of 1,188
      recognizable images of a list of nevi of the skin was undertaken in order to
      delineate a classification of the various shapes and patterns of nevi. We
      disclosed three distinct shapes and two so far undescribed archetypical patterns,
      in addition to the well-known Blaschko-linear, flag-like and extensive garment
      like patterns, to which all lesions could be allocated. The newly delineated
      shapes are called round or oval shape; patches with indented borders; and
      teardrop or triangular shape. The newly proposed archetypical configurations are
      the agminated pattern and the diffuse patchy pattern. Other mosaic patterns, such
      as the phylloid pattern or the lateralization pattern, were not observed in any
      of the images reviewed. We conclude that the various types of nevi can be
      assigned to specific shapes or patterns. Admittedly, however, a given nevus may
      manifest itself in several different shapes, whereas its archetypical pattern
      tends to be the same. This 'archetypical' pattern can be taken as the perfect or
      ideal model of a given type of nevus, whereas the newly described shapes are
      subordinated to the archetypical patterns and are best considered to be
      'nonarchetypical'. Our work gives more consistency to the idea that nevi reflect
      mosaicism, because they display repetitive shapes and patterns.

PMID- 16280297
TI  - Desmoplastic hairless hypopigmented nevus (DHHN). A distinct variant of giant
      melanocytic nevus.
AB  - Desmoplastic hairless hypopigmented nevus (DHHN) is the name Ruiz-Maldonado et
      al. gave to a new variant of giant congenital melanocytic nevus characterized
      clinically by a hard ligneous consistency, absence of hair and progressive loss
      of pigment. Histologically, dermal fibrosis consistent with desmoplasia is a
      predominant feature. We describe a 6-year-old boy with a hard hairless pigmented
      congenital nevus involving the lumbosacral area, buttocks, perineum and scrotum.
      During the first years of life, the nevus showed a progressive reduction in
      colour, size and consistency. These changes continued until the age of four when
      a well-demarcated tumour appeared, within the nevus, on the right buttock.
      Resection of this outgrowth was performed. Histologically, nevus cells of normal
      appearance between thick collagen bundles were present. Immunostaining revealed
      S100 +, Vim +, HMB45--results. The nevus has continued to involute to date. An
      immune response against the melanocytes of the nevus may explain this type of
      evolution.

PMID- 16280298
TI  - The role of lesional T cells in recalcitrant psoriasis during infliximab therapy.
AB  - With infliximab therapy (anti-TNF-alpha) for plaque psoriasis, over 80% of
      patients reach > or = 75% PASI improvement in 10 weeks of treatment. We describe
      a patient with severe recalcitrant psoriasis who was treated with infliximab 5
      mg/kg for 22 weeks. Rather than the expected improvement, this patient
      experienced an initial exacerbation, followed by the lack of efficacy over the
      entire 22-week period of treatment. Before, during and after treatment we
      performed immunohistochemical analyses on lesional biopsies, with respect to T
      cells, NK-T cells, epidermal growth and differentiation. We found a discrepancy
      between the clinical aggravation and marked reductions of lesional T cell
      subsets. The most prominent decrease was for CD4+ T cells (72-74%), which
      suggests that a reduction of T cells in the psoriatic plaque might not be a
      guarantee for positive clinical outcomes. Remarkably, the number of epidermal
      CD94+ NK-T cells correlated fairly well with the lack of clinical efficacy,
      supposing a pathogenic role for these cells in psoriasis. Further studies are
      needed to clarify the ambiguous role of conventional pathogenic T cells in plaque
      psoriasis.

PMID- 16280300
TI  - Microvessel density and HIF-1alpha expression correlate with malignant potential
      in fibrohistiocytic tumors.
AB  - Angiogenesis is a central process in the growth of solid tumors. Hypoxia
      inducible factor-1alpha (HIF-1alpha) is an oxygen-dependent transcriptional
      activator, which plays a crucial role in tumor angiogenesis. However, involvement
      of HIF-1alpha has never been studied in so-called fibrohistiocytic tumors, such
      as dermatofibroma (DF), dermatofibrosarcoma protuberans (DFSP) and malignant
      fibrous histiocytoma (MFH). We analyzed the extents of angiogenesis in relation
      to the expression levels of HIF-1alpha in 26 DF, 13 DFSP and 23 MFH cases. MFH
      showed significantly higher microvessel density (MVD) compared with DF and DFSP.
      Immunohistochemically, HIF-1alpha-positive cases constituted 31%, 15% and 98% of
      DF, DFSP and MFH, respectively, indicating significantly higher HIF-1alpha
      expression in MFH compared with DF and DFSP. Furthermore, MFH cases expressing
      high levels of HIF-1alpha showed significantly higher MVD than those with low
      levels of HIF-1alpha. Thus, higher levels of angiogenesis and HIF-1alpha
      expression are both closely associated with the malignant potential in so-called
      fibrohistiocytic tumors, and HIF-1alpha is possibly involved in angiogenesis in
      MFH.

PMID- 16280299
TI  - Comedolytic effect of a novel RARgamma-specific retinoid, ER36009: comparison
      with retinoic acid in the rhino mouse model.
AB  - In addition to natural retinoids, new synthetic retinoids, such as adapalene and
      tazarotene, are currently available for the treatment of acne. In this study, we
      evaluated the comedolytic effect of a novel retinoic acid receptor (RAR)-gamma
      specific retinoid, ER36009, in the rhino mouse. The animals were treated for five
      days a week with ER36009 (0.00001, 0.000025, 0.00010, 0.00025%), all-trans
      retinoic acid (RA) (0.001, 0.005, 0.010, 0.050%), two commercial formulations
      (Differine((R)) 0.1% adapalene gel, and Tazorac 0.1% tazarotene gel) and acetone
      as a control, for two weeks. After the treatments, utricle diameter and apoptosis
      of the follicular epidermis were examined. ER36009 was 96 times more potent than
      RA in the utricle diameter reduction assay. It also eliminated apoptosis of the
      follicular epidermis and restored normal apoptosis at the granular layer. These
      data indicate that ER36009 is a potent comedolytic agent compared with other
      currently available retinoids.

PMID- 16280301
TI  - A comparative non randomized study of narrow-band (NB) (312 +/- 2 nm) UVB
      phototherapy versus sequential therapy with oral administration of low-dose
      Cyclosporin A and NB-UVB phototherapy in patients with severe psoriasis vulgaris.
AB  - Sequential therapy may improve the efficacy and safety of single treatments for
      severe psoriasis. We compared sequential Cyclosporin A and narrow-band UVB
      phototherapy versus narrow-band UVB phototherapy alone. A group of 30 patients
      with severe psoriasis received 3 mg/kg/day Cyclosporin A for 4 weeks. Afterwards,
      Cyclosporin A was rapidly tapered and phototherapy begun. An additional 30
      patients received phototherapy alone. Treatments were given until psoriasis
      cleared or until partial improvement was achieved without further amelioration
      despite another week of treatment. Both treatments were highly effective and well
      tolerated but sequential therapy was more effective in lesions of UV-shielded
      body areas; itching disappeared more quickly. The cumulative narrow-band UVB
      dosages and number of exposures were lower. No difference was seen at follow-up
      extended up to 9 months. Sequential therapy was well tolerated and allowed for
      the reduction of narrow-band UVB dosage and exposures, quick relief of itching
      and improvement of UV-shielded lesions.

PMID- 16280302
TI  - Radiotherapy in multilocalized lymphedema-associated angiosarcoma.
AB  - We report an 80-year-old woman, suffering from a recurrence of a multilocalized
      lymphedema-associated angiosarcoma of the right arm. The tumor consisted of solid
      tumor cell formations and "classical" spongiform tumor complexes. In the tumor
      periphery, pathological endothelial cell proliferates on pre-existing dilated
      lymphatic capillaries were detectable, which, together with immunohistology (CD
      31+/Desmoplakin-1-2.17+/CD 34-), supported the diagnosis of lymphangiosarcoma.
      Complete remission was achieved under radioimmunotherapy (54 Gy/Interferon beta).
      A further recurrence 3 months later outside the primary therapy fields was
      successfully treated with radiotherapy alone. During a follow-up observation
      period of 3 years, there was neither local recurrence nor metastasis. This case
      demonstrates for the first time the long-lasting efficacy of photon radiation in
      a case of histologically-defined lymphangiosarcoma. Further studies should
      elucidate the suitability of radio monotherapy as first-line therapy in
      lymphedema-associated angiosarcoma with lymphatic endothelium-like
      immunohistology.

PMID- 16280303
TI  - Lymphatic mapping and sentinel lymphonodectomy in recurrent cutaneous squamous
      cell carcinomas.
AB  - There are subsets of cutaneous squamous cell carcinoma (SCC), including recurrent
      tumours, that have a high-risk for both local recurrence and metastasis. Since
      the presence of regional lymph node metastases carries a poor prognosis, the
      early evaluation of the nodal status is crucial for staging and treatment
      planning. Recent trials have shown that the lymphatic mapping (LM) and sentinel
      lymphonodectomy (SLNE) may be successfully employed to screen nodal basins in
      patients with high-risk cutaneous SCCs at clinical stage N0. We report our
      experience with this procedure in five selected patients affected with recurrent
      cutaneous SCCs. A metastatic sentinel lymph node (SLN) was found in 1 of the 5
      cases. No false negative result was observed. SLNE is a feasible and minimally
      invasive staging procedure in patients with high-risk cutaneous SCCs. It may
      select patients with clinically occult metastases in the regional nodal basins,
      who can be submitted to therapeutic lymph node dissection (LND), avoiding the
      morbidity of a prophylactic LND in patients without metastases in SLNs.

PMID- 16280304
TI  - Primary cutaneous marginal zone B-cell lymphoma.
AB  - We report a Japanese case of primary cutaneous marginal zone B-cell lymphoma
      (PCMZL). This 46-year-old woman presented with a subcutaneous nodule on her right
      forearm. With the combined morphology,the immunophenotype, and molecular
      analysis, we diagnosed this lesion as PCMZL. Furthermore, we reviewed the 16
      cases of PCMZL in the Japanese literature. The ages of the patients ranged from
      26 to 75 years (mean 55.7 years) with a slight female predilection. Clinically,
      most of the skin lesions were erythematous nodular lesions. The involved regions
      were the face and neck in eight cases, the trunk in six and the arms in five.
      None had Borrelia burgdorferi infection or a history of thyroiditis. Two patients
      had suffered from Sjogren's syndrome. Histopathologically, lymphoepithelial
      lesions were found in nine cases. The chromosomal aberrations in MALT lymphoma
      such as t(11;18)(q21;q21), t(14;18)(q32;q21) and t(3;14)(p14.1;q32) were not
      reported in any of the Japanese cases. Although two patients developed metastasis
      on the skin after radiation therapy, none died of lymphoma.

PMID- 16280305
TI  - A prospective study of the responsiveness of depression and suicidal ideation in
      acne patients to different phases of isotretinoin therapy.
AB  - The degree and manner to which isotretinoin affects the mental health of acne
      patients has not been extensively researched, despite reports of possible
      associations between isotretinoin and depression. In this study, 33 patients with
      acne were prescribed a standard 16-week treatment regime with isotretinoin. At
      the initiation of isotretinoin treatment, week 8 review and termination of
      treatment, patients completed validated measures of depression, hopelessness and
      self-rated dermatological severity and were also assessed dermatologically using
      an acne grading protocol. When the first phase of isotretinoin treatment (week 1
      to week 8) was compared to the second phase (week 9 to week 16), patients
      reported significant improvements in the cognitive-affective features of
      depression during the first phase of treatment, but not during the second phase.
      Corresponding improvements in the somatic symptoms of depression and hopelessness
      were not found. The implications of the research are discussed in relation to
      methodological design issues in this area.

PMID- 16280306
TI  - Mycosis fungoides presenting as pigmented purpuric eruption.
AB  - A case of pigmented purpuric eruptions evolving to mycosis fungoides during the 4
      year follow-up period is described. Clinical manifestation was characterized by
      petechial lesions with irregular shaped, diffusely pigmented plaques partly
      sharing morphological similarities with chronic pigmented purpura.
      Histologically, lymphocytes infiltrated around the capillaries of the superficial
      dermis with extravasated erythrocytes as well as into the epidermis to form
      Pautrier microabscesses. Whereas CD4+ cells were observed in the epidermis and
      upper dermis, CD8+ cells tended to be distributed around the capillaries.
      Notably, the Rumpel-Leede test revealed extensive punctuate purpura limited to
      the lesional skin. The aggregation response of platelets was not impaired. Either
      CD4+ tumor lymphocytes or CD8+ reactive lymphocytes appeared to induce capillary
      damage resulting in the formation of petechial lesions. Pigmented purpuric
      eruptions, such as atypical chronic pigmented purpura, is thus an important
      initial clinical manifestation of mycosis fungoides.

PMID- 16280307
TI  - Sister Mary Joseph's nodule: a clue to finding pancreatic cancer in a patient
      previously affected by gastric cancer.
AB  - An 82-year-old man with Sister Mary Joseph's nodule (SMJN) is reported. He had a
      past history of gastric cancer, which had been removed in its early stage.
      Histopathological findings, in which CA19-9 and other markers, such as PCNA and
      p53, were strongly positive in SMJN but negative in specimens from the gastric
      cancer, suggested that the nodule had derived from another internal malignancy
      and a detailed search led to the discovery of a pancreatic cancer.

PMID- 16280308
TI  - Trombiculiasis: clinical contribution.
AB  - Neotrombicula autumnalis is an arthropod usually living in the soil, except for
      the short period of the larval stage when it becomes a real parasite of warm
      blooded hosts. We present a case of human trombiculiasis, which is unusual
      because of the parasite transmission from animals to humans, as in a typical
      synanthropic dermatosis.

PMID- 16280309
TI  - Rapid onset of acute carcinoma of the glans penis arising three years after a
      lichen sclerosus.
AB  - Lichen sclerosus and atrophicus (LSA) is an inflammatory disease of incompletely
      characterised pathogenesis. If the development of squamous cell carcinoma (SCC)
      during the evolution of LSA is well described in women, this complication is a
      matter of discussion in men. We report an unusual case of acute and aggressive
      SCC which complicated the evolution of an LSA of the glans penis within three
      years. This type of observation is rarely reported in the medical literature.

PMID- 16280310
TI  - Atopic eczema complicated by systemic lupus erythematosus.
AB  - We report two patients with atopic eczema (AE), who developed systemic lupus
      erythematosus (SLE). Case 1 was a 25-year-old man who developed SLE during
      treatment of AE in our department. He had a positive antinuclear antibody (ANA)
      (1:640), anti-ssDNA, anti-SSA and anti-RNP. Case 2 was a 27-year-old man who had
      a past history of AE. He developed SLE and had a positive ANA (1:320), anti
      ssDNA, anti-dsDNA and anti-SSA. Among 33 patients with SLE in our department,
      four had suffered from AE (12%). There have been a few reports of AE complicated
      by SLE. Even if it is very rare, like case 1, that two morbid conditions, AE and
      SLE simultaneously exist in an individual, our findings suggest that it is
      necessary to measure various autoantibodies in ANA (+) patients with AE and to
      carefully monitor those patients for long-term development of SLE symptoms if
      other autoantibodies are positive.

PMID- 16280311
TI  - Fatal natural killer cell lymphoma arising in a patient with a crop of Epstein
      Barr virus-associated disorders.
AB  - Natural killer (NK) lymphoma in Asia is frequently associated with latent Epstein
      Barr (EBV) infection. Unlike the adult cases, EBV-associated NK/T cell lymphomas
      in children are often preceded by various EBV-related disorders, including
      chronic active EBV infection (CAEBV), hypersensitivity to mosquito bites (HMB),
      virus-associated haemophagocytic syndrome (VAHS), and hydroa vacciniforme (HV)
      like eruptions. Here, we report a 14-year-old Japanese girl who sequentially
      developed all the symptoms related to EBV-associated NK/T cell
      lymphoproliferative disorders in a 12-year clinical course. Our observations
      confirm the spectrum of EBV-associated cutaneous disorders and indicate the
      importance of long-term follow-up.

PMID- 16280312
TI  - Coordination dynamics of the horse-rider system.
AB  - The authors studied the interaction between rider and horse by measuring their
      ensemble motions in a trot sequence, comparing 1 expert and 1 novice rider.
      Whereas the novice's movements displayed transient departures from phase
      synchrony, the expert's motions were continuously phase-matched with those of the
      horse. The tight ensemble synchrony between the expert and the horse was
      accompanied by an increase in the temporal regularity of the oscillations of the
      trunk of the horse. Observed differences between expert and novice riders
      indicated that phase synchronization is by no means perfect but requires extended
      practice. Points of contact between horse and rider may haptically convey
      effective communication between them.

PMID- 16280313
TI  - Emotion and motor control: movement attributes following affective picture
      processing.
AB  - The authors investigated the impact of emotion on the performance of a square
      tracing task after participants (N = 40) were exposed to pleasant (P), unpleasant
      (U), and neutral (N) pictures. Physiological and self-report measures indexed
      affective valence and arousal. In Experiment 1, greater error followed exposure
      to 4 consecutive U images than exposure to 4 consecutive P images. Speed of
      performance did not vary as a function of valence. In Experiment 2, participants
      viewed 1 slide per trial within a modified exposure protocol. Speed of
      performance varied as a function of valence; faster performance followed U
      relative to P stimuli. Accuracy of performance did not vary between conditions.
      Corresponding self-report and physiological measures generally corroborated
      previous evidence. Findings collectively indicated that the length of exposure to
      affective stimuli mediates speed and accuracy of motor performance; compared with
      P stimuli, U stimuli led to either increased error (short exposure) or increased
      speed (multiple exposures). The authors conclude that brief and extended
      exposures to affective pictures have direct behavioral consequences, and they
      discuss the implications of that finding.

PMID- 16280314
TI  - Deliberate control of continuous motor performance.
AB  - The authors examined the means by which people vary movement parameters to
      satisfy more than 1 constraint at a time in a repetitive motor task. The authors
      expected that when participants (N = 12) were simultaneously confronted with
      spatial and temporal constraints in an ellipse-drawing task, they would either
      exploit the intrinsic amplitude-frequency relationships or activate less natural
      control regimes to prioritize their movement goals. By focusing on local
      amplitude and frequency errors and parameter changes from 1 movement to the next,
      the authors distinguished parameter changes that reflected exploitation of
      biomechanics from those that required deliberate control. The findings
      demonstrated that at low movement speeds, participants can pursue multiple
      movement goals simultaneously; at higher speeds, their capacity to satisfy
      multiple task goals is reduced. The authors used a new method of inferring
      deliberate control from movement kinematics in the present study.

PMID- 16280315
TI  - Timing precision in circle drawing does not depend on spatial precision of the
      timing target.
AB  - The authors manipulated the width of a timing target in continuous circle drawing
      to determine whether a more stringent spatial-timing criterion would produce an
      increase in participants' (N = 30) temporal variability. They also examined the
      effect of the computational method of determining cycle duration. There was no
      effect of spatial precision on temporal variability in circle drawing, and
      tapping and circle drawing were found to use the same criterion. Those findings
      lend strong support to the earlier view of R. B. Ivry, R. M. Spencer, H. N.
      Zelaznik, and J. Diedrichsen (2002), who argued that continuous tasks such as
      circle drawing are timed differently from discrete-like tasks such as tapping.
      Therefore, the results of the present study provide support for the event and
      emergent timing frameworks.

PMID- 16280316
TI  - Plane of motion mediates the coalition of constraints in rhythmic bimanual
      coordination.
AB  - The authors hypothesized that the modulation of coordinative stability and
      accuracy caused by the coalition of egocentric (neuromuscular) and allocentric
      (directional) constraints varies depending on the plane of motion in which
      coordination patterns are performed. Participants (N = 7) produced rhythmic
      bimanual movements of the hands in the sagittal plane (i.e., up-and-down
      oscillations resulting from flexion-extension of their wrists). The timing of
      activation of muscle groups, direction of movements, visual feedback, and across
      trial movement frequency were manipulated. Results showed that both the
      egocentric and the allocentric constraints modulated pattern stability and
      accuracy. However, the allocentric constraint played a dominant role over the
      egocentric. The removal of vision only slightly destabilized movements,
      regardless of the effects of directional and (neuro)muscular constraints. The
      results of the present study hint at considering the plane in which coordination
      is performed as a mediator of the coalition of egocentric and allocentric
      constraints that modulates coordinative stability of rhythmic bimanual
      coordination.

PMID- 16280317
TI  - Transfer, control, and automatic processing in a complex motor task: an
      examination of bounce juggling.
AB  - The authors evaluated the hypothesis that controlled and automatic processes are
      opposite ends of a continuum of learning (e.g., R. M. Shiffrin & W. Schneider,
      1977) vs. an alternative, concurrent emergence hypothesis (e.g., J. M. Bebko et
      al., 2003; G. Logan, 1989). The authors also measured potential positive transfer
      effects of learning from one motor task to another. Four experienced cascade
      jugglers and 5 novices learned to bounce juggle, practicing regularly for 5
      weeks. The experienced jugglers showed positive transfer of learning, maintaining
      a lead of approximately 6-10 days over the novices, even as both groups
      automatized the new skill. Measures of automatic and controlled processing were
      positively correlated, indicating that those processes emerge concurrently. The
      authors present a model in which controlled and automatic processes emerge
      orthogonally.

PMID- 16280318
TI  - EMG activity in selected target muscles during imagery rising on tiptoes in
      healthy adults and poststroke hemiparetic patients.
AB  - The authors sought to gain further knowledge about activation of target muscles
      during imagery engagement in a motor task. Six hemiparetic patients and 9 healthy
      participants performed 3 real rises on tiptoes and then, after pausing, 3 imagery
      rises on tiptoes. Metronome beats guided the rate of rises and descents.
      Electromyographic (EMG) activity from the medial gastrocnemius and the rectus
      femoris muscles were monitored bilaterally throughout the performance of both
      tasks. In 3 healthy participants and 3 individuals with hemiparesis, EMG activity
      was related to the imagery task in at least 1 of the target muscles. Conversely,
      in the other participants, motor imagery practice was not accompanied by task
      related EMG activity in the monitored muscles. In all cases, the increment in
      activation level during motor imagery practice was very low in comparison with
      that of real performance. The findings were not unequivocal; therefore, EMG
      activity may sometimes, but not always, be recorded during motor imagery practice
      both in healthy individuals and in poststroke hemiparetic participants. Further
      research is needed to align motor imagery practice with the objectives of motor
      rehabilitation.

PMID- 16280319
TI  - The human motor control system's response to mechanical perturbation: should it,
      can it, and does it ensure stability?
AB  - From among the diverse meanings of stability, the one the author adopts here is
      that the effects of a perturbation are opposed, and therefore small effects
      remain small. Except in linear systems, however, instability need not lead to
      unbounded motion and may actually be desirable when maneuverability is important.
      Moreover, properties of nerves, muscles, and tendons present serious challenges
      to stabilization. A review of observations from the motor control literature
      reveals that responses to perturbations in many common situations assist rather
      than resist the perturbation and are therefore presumably destabilizing. The
      observations encompass situations of position maintenance as well as impending or
      ongoing movement. The author proposes that the motor control system responds to a
      sudden perturbation by a pattern of muscle activity that mimics an accustomed
      voluntary movement, oblivious of stability considerations. What prevents runaway
      motion in the face of short-term instability appears to be voluntary
      intervention.

PMID- 16280320
TI  - DPM1, the catalytic subunit of dolichol-phosphate mannose synthase, is tethered
      to and stabilized on the endoplasmic reticulum membrane by DPM3.
AB  - Dolichol-phosphate mannose (DPM) synthase is required for synthesis of the
      glycosylphosphatidylinositol (GPI) anchor, N-glycan precursor, protein O-mannose,
      and C-mannose. We previously identified DPM3, the third component of this enzyme,
      which was co-purified with DPM1 and DPM2. Here, we have established mutant
      Chinese hamster ovary (CHO) 2.38 cells that were defective in DPM3. CHO2.38 cells
      were negative for GPI-anchored proteins, and microsomes from these cells showed
      no detectable DPM synthase activity, indicating that DPM3 is an essential
      component of this enzyme. A coiled-coil domain near the C terminus of DPM3 was
      important for tethering DPM1, the catalytic subunit of the enzyme, to the
      endoplasmic reticulum membrane and, therefore, was critical for enzyme activity.
      On the other hand, two transmembrane regions in the N-terminal portion of DPM3
      showed no specific functions. DPM1 was rapidly degraded by the proteasome in the
      absence of DPM3. Free DPM1 was strongly associated with the C terminus of Hsc70
      interacting protein (CHIP), a chaperone-dependent E3 ubiquitin ligase, suggesting
      that DPM1 is ubiquitinated, at least in part, by CHIP.

PMID- 16280321
TI  - The heat shock protein 90-CDC37 chaperone complex is required for signaling by
      types I and II interferons.
AB  - Interferon signaling pathways are critical to both innate and adaptive immunity.
      We have demonstrated here that the inhibition of heat shock protein 90 (Hsp90)
      functions by small interfering RNAs or chemical inhibitors blocking interferon
      induced gene expression. Hsp90 was required for signal transducers and activators
      of transcription 1 phosphorylation, and in its absence, Janus kinase (JAK) 1/2
      were degraded by the proteosome. JAK1 interacts with Hsp90 and the CDC37 co
      chaperone, and both interactions are destabilized by Hsp90 inhibitors. The
      biological consequences were suggested by experiments showing that T cell
      activation by interferon-gamma-primed macrophages and the antiviral response of
      interferons required Hsp90. We conclude that JAK1/2 are client proteins of Hsp90
      and that Hsp90 and CDC37 play a critical role in types I and II interferon
      pathways.

PMID- 16280322
TI  - In vitro transport of membrane proteins to peroxisomes by shuttling receptor
      Pex19p.
AB  - The peroxin Pex19p comprising 299 amino acids functions in peroxisomal membrane
      assembly. We here developed a cell-free system for transport of membrane proteins
      to peroxisomes. Pex19p interacts with multiple membrane peroxins, including other
      membrane biogenesis peroxins, Pex16p and Pex26p, involved in matrix protein
      import. Cell-free synthesized, 35S-labeled Pex19p was targeted to subcellular
      fractions containing peroxisomes from Chinese hamster ovary-K1 cells as well as
      peroxisomes isolated from rat liver in an ATP-dependent manner. Such
      translocation was also reproduced with in vitro synthesized 35S-Pex16p with two
      transmembrane segments and C-tail anchor-type 35S-Pex26p, upon incubation with
      35S-Pex19p in the reaction mixtures containing isolated peroxisomes. The
      transported 35S-Pex16p and 35S-Pex26p were integrated into membranes as assessed
      by the sodium carbonate extraction method. Peroxisome-associated and partly
      Na2CO3-resistant 35S-Pex19p was released to the cytosolic fraction upon
      incubation in the absence of ATP, whereas 35S-Pex16p and 35S-Pex26p remained in
      the membranes. Furthermore, not only 35S-Pex19p but also 35S-Pex19p complexes
      each with 35S-Pex16p and 35S-Pex26p were bound to 35S-Pex3p in vitro. Together,
      these results strongly suggested that Pex19p translocates the membrane peroxins
      from the cytosol to peroxisomes in an ATP- and Pex3p-dependent manner and then
      shuttles back to the cytosol.

PMID- 16280325
TI  - WITHDRAWN: Phosphorylation of dead-box RNA helicase DDX3 by mitotic cyclin
      B/CDC2, but not cyclin A/CDK2.
AB  - Withdrawn by the Author.

PMID- 16280323
TI  - beta-arrestin-dependent, G protein-independent ERK1/2 activation by the beta2
      adrenergic receptor.
AB  - Physiological effects of beta adrenergic receptor (beta2AR) stimulation have been
      classically shown to result from G(s)-dependent adenylyl cyclase activation. Here
      we demonstrate a novel signaling mechanism wherein beta-arrestins mediate beta2AR
      signaling to extracellular-signal regulated kinases 1/2 (ERK 1/2) independent of
      G protein activation. Activation of ERK1/2 by the beta2AR expressed in HEK-293
      cells was resolved into two components dependent, respectively, on G(s)
      G(i)/protein kinase A (PKA) or beta-arrestins. G protein-dependent activity was
      rapid, peaking within 2-5 min, was quite transient, was blocked by pertussis
      toxin (G(i) inhibitor) and H-89 (PKA inhibitor), and was insensitive to depletion
      of endogenous beta-arrestins by siRNA. beta-Arrestin-dependent activation was
      slower in onset (peak 5-10 min), less robust, but more sustained and showed
      little decrement over 30 min. It was insensitive to pertussis toxin and H-89 and
      sensitive to depletion of either beta-arrestin1 or -2 by small interfering RNA.
      In G(s) knock-out mouse embryonic fibroblasts, wild-type beta2AR recruited beta
      arrestin2-green fluorescent protein and activated pertussis toxin-insensitive
      ERK1/2. Furthermore, a novel beta2AR mutant (beta2AR(T68F,Y132G,Y219A) or
      beta2AR(TYY)), rationally designed based on Evolutionary Trace analysis, was
      incapable of G protein activation but could recruit beta-arrestins, undergo beta
      arrestin-dependent internalization, and activate beta-arrestin-dependent ERK.
      Interestingly, overexpression of GRK5 or -6 increased mutant receptor
      phosphorylation and beta-arrestin recruitment, led to the formation of stable
      receptor-beta-arrestin complexes on endosomes, and increased agonist-stimulated
      phospho-ERK1/2. In contrast, GRK2, membrane translocation of which requires
      Gbetagamma release upon G protein activation, was ineffective unless it was
      constitutively targeted to the plasma membrane by a prenylation signal (CAAX).
      These findings demonstrate that the beta2AR can signal to ERK via a GRK5/6-beta
      arrestin-dependent pathway, which is independent of G protein coupling.

PMID- 16280324
TI  - Conserved role of the linker alpha-helix of the bacterial disulfide isomerase
      DsbC in the avoidance of misoxidation by DsbB.
AB  - In the bacterial periplasm the co-existence of a catalyst of disulfide bond
      formation (DsbA) that is maintained in an oxidized state and of a reduced enzyme
      that catalyzes the rearrangement of mispaired cysteine residues (DsbC) is
      important for the folding of proteins containing multiple disulfide bonds. The
      kinetic partitioning of the DsbA/DsbB and DsbC/DsbD pathways partly depends on
      the ability of DsbB to oxidize DsbA at rates >1000 times greater than DsbC. We
      show that the resistance of DsbC to oxidation by DsbB is abolished by deletions
      of one or more amino acids within the alpha-helix that connects the N-terminal
      dimerization domain with the C-terminal thioredoxin domain. As a result, mutant
      DsbC carrying alpha-helix deletions could catalyze disulfide bond formation and
      complemented the phenotypes of dsbA cells. Examination of DsbC homologues from
      Haemophilus influenzae, Pseudomonas aeruginosa, Erwinia chrysanthemi, Yersinia
      pseudotuberculosis, Vibrio cholerae (30-70% sequence identity with the
      Escherichia coli enzyme) revealed that the mechanism responsible for avoiding
      oxidation by DsbB is a general property of DsbC family enzymes. In addition we
      found that deletions in the linker region reduced, but did not abolish, the
      ability of DsbC to assist the formation of active vtPA and phytase in vivo, in a
      DsbD-dependent manner, revealing that interactions between DsbD and DsbC are also
      conserved.

PMID- 16280326
TI  - Glutamic acid-rich proteins of rod photoreceptors are natively unfolded.
AB  - The outer segment of vertebrate photoreceptors is a specialized compartment that
      hosts all the signaling components required for visual transduction. Specific to
      rod photoreceptors is an unusual set of three glutamic acid-rich proteins (GARPs)
      as follows: two soluble forms, GARP1 and GARP2, and the N-terminal cytoplasmic
      domain (GARP' part) of the B1 subunit of the cyclic GMP-gated channel. GARPs have
      been shown to interact with proteins at the rim of the disc membrane. Here we
      characterized native GARP1 and GARP2 purified from bovine rod photoreceptors.
      Amino acid sequence analysis of GARPs revealed structural features typical of
      "natively unfolded" proteins. By using biophysical techniques, including size
      exclusion chromatography, dynamic light scattering, NMR spectroscopy, and
      circular dichroism, we showed that GARPs indeed exhibit a large degree of
      intrinsic disorder. Analytical ultracentrifugation and chemical cross-linking
      showed that GARPs exist in a monomer/multimer equilibrium. The results suggested
      that the function of GARP proteins is linked to their structural disorder. They
      may provide flexible spacers or linkers tethering the cyclic GMP-gated channel in
      the plasma membrane to peripherin at the disc rim to produce a stack of rings of
      these protein complexes along the long axis of the outer segment. GARP proteins
      could then provide the environment needed for protein interactions in the rim
      region of discs.

PMID- 16280327
TI  - A pathway for tumor necrosis factor-alpha-induced Bcl10 nuclear translocation.
      Bcl10 is up-regulated by NF-kappaB and phosphorylated by Akt1 and then complexes
      with Bcl3 to enter the nucleus.
AB  - Bcl10 overexpression and nuclear translocation were originally identified in
      mucosa-associated lymphoid tissue lymphoma with t(1;14)(p32;q32) chromosome
      translocation. DNA amplification of Bcl10 was also found in other solid tumors.
      We have recently shown that nuclear translocation of Bcl10 is a specific
      molecular determinant of Helicobacter pylori-independent mucosa-associated
      lymphoid tissue lymphoma (Kuo, S.-H., Chen, L. T., Yeh, K.-H., Wu, M. S., Hsu, H.
      C., Yeh, P. Y., Mao, T. L., Chen, C. L., Doong, S. L., Lin, J. T., and Cheng, A.
      L. (2004) J. Clin. Oncol. 22, 3491-3497). However, the molecular mechanism of
      Bcl10 nuclear translocation remains unknown. In this study, we observed that
      tumor necrosis factor-alpha (TNFalpha) up-regulates the expression of Bcl10 and
      induces a fraction of Bcl10 nuclear translocation in human breast carcinoma MCF7
      cells. Chromatin immunoprecipitation assays and electrophoretic mobility shift
      assays indicated that an NF-kappaB-binding site resides in the Bcl10 5 '
      untranslated region. This study also demonstrates that Akt1, activated by
      TNFalpha, phosphorylates Bcl10 at Ser218 and Ser231 and that phosphorylated Bcl10
      subsequently complexes with Bcl3 to enter the nucleus. Either inhibition of Akt1
      or depletion of Bcl3 blocks Bcl10 nuclear translocation. In summary, these
      findings characterize a molecular linkage that directs Bcl10 nuclear
      translocation in response to TNFalpha treatment.

PMID- 16280328
TI  - MCP-1-induced human osteoclast-like cells are tartrate-resistant acid
      phosphatase, NFATc1, and calcitonin receptor-positive but require receptor
      activator of NFkappaB ligand for bone resorption.
AB  - MCP-1 (monocyte chemotactic protein-1) is a CC chemokine that is induced by
      receptor activator of NFkappaB ligand (RANKL) in human osteoclasts. In the
      absence of RANKL, treatment of human peripheral blood mononuclear cells with
      macrophage colony-stimulating factor and MCP-1 resulted in tartrate-resistant
      acid phosphatase (TRAP)-positive multinuclear cells that are positive for
      calcitonin receptor (CTR) and a number of other osteoclast markers, including
      nuclear factor of activated t cells, cytoplasmic, calcineurin-dependent 1
      (NFATc1). Although NFATc1 was strongly induced by MCP-1 and was observed in the
      nucleus, MCP-1 did not permit the formation of bone-resorbing osteoclasts,
      although these cells had the typical TRAP(+)/CTR(+) multinuclear phenotype of
      osteoclasts. Despite a similar appearance to osteoclasts, RANKL treatment was
      required in order for TRAP(+)/CTR(+) multinuclear cells to develop bone
      resorption activity. The lack of bone resorption was correlated with a deficiency
      in expression of certain genes related to bone resorption, such as cathepsin K
      and MMP9. Furthermore, calcitonin blocked the MCP-1-induced formation of
      TRAP(+)/CTR(+) multinuclear cells as well as blocking osteoclast bone resorption
      activity, indicating that calcitonin acts at two stages of osteoclast
      differentiation. Ablation of NFATc1 in mature osteoclasts did not prevent bone
      resorption activity, suggesting NFATc1 is involved in cell fusion events and not
      bone resorption. We propose that the MCP-1-induced TRAP(+)/CTR(+) multinuclear
      cells represent an arrested stage in osteoclast differentiation, after NFATc1
      induction and cellular fusion but prior to the development of bone resorption
      activity.

PMID- 16280329
TI  - The C-terminal activating region 2 of the Epstein-Barr virus-encoded latent
      membrane protein 1 activates NF-kappaB through TRAF6 and TAK1.
AB  - Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is oncogenic
      and indispensable for EBV-mediated B cell transformation. LMP1 is capable of
      activating several intracellular signaling pathways including the NF-kappaB
      pathway, which contributes to the EBV-mediated cell transformation. Two regions
      in the cytoplasmic carboxyl tail of LMP1, namely C-terminal activating regions 1
      and 2 (CTAR1 and CTAR2), are responsible for NF-kappaB activation, with CTAR2
      being the main NF-kappaB activator. Although the CTAR1-mediated NF-kappaB
      activation was previously shown to be TRAF3-dependent, we showed here that the
      CTAR2-mediated NF-kappaB activation is mainly TRAF6-dependent but TRAF2/5
      independent. In contrast to the interleukin-1 receptor/toll-like receptor
      mediated NF-kappaB pathways, the CTAR2-mediated NF-kappaB pathway does not
      require MyD88, IRAK1, or IRAK4 for TRAF6 engagement. Furthermore, we showed that
      TAK1 is required for NF-kappaB activation by LMP1. Thus, LMP1 utilizes two
      distinct pathways to activate NF-kappaB: a major one through
      CTAR2/TRAF6/TAK1/IKKbeta (canonical pathway) and a minor one through
      CTAR1/TRAF3/NIK/IKKalpha (noncanonical pathway).

PMID- 16280332
TI  - Challenges in advancing mental and physical health of patients with serious
      mental illness.

PMID- 16280330
TI  - Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP and PC-3
      prostate epithelial cells.
AB  - Sulforaphane (SFN), an isothiocyanate first isolated from broccoli, exhibits
      chemopreventive properties in prostate cancer cells through mechanisms that are
      poorly understood. We recently reported on a novel mechanism of chemoprotection
      by SFN in human colon cancer cells, namely the inhibition of histone deacetylase
      (HDAC). Here, we show that addition of 15 microM SFN also inhibited HDAC activity
      by 40, 30 and 40% in BPH-1, LnCaP and PC-3 prostate epithelial cells,
      respectively. The inhibition of HDAC was accompanied by a 50-100% increase in
      acetylated histones in all three prostate cell lines, and in BPH-1 cells treated
      with SFN there was enhanced interaction of acetylated histone H4 with the
      promoter region of the P21 gene and the bax gene. A corresponding 1.5- to 2-fold
      increase was seen for p21Cip1/Waf1 and Bax protein expression, consistent with
      previous studies using HDAC inhibitors, such as trichostatin A. The downstream
      events included cell cycle arrest and activation of apoptosis, as evidenced by
      changes in cell cycle kinetics and induction of multi-caspase activity. These
      findings provide new insight into the mechanisms of SFN action in benign prostate
      hyperplasia, androgen-dependent prostate cancer and androgen-independent prostate
      cancer cells, and they suggest a novel approach to chemoprotection and
      chemotherapy of prostate cancer through the inhibition of HDAC.

PMID- 16280331
TI  - Defined genetic events associated with the spontaneous in vitro transformation of
      ElA/Ras-expressing human IMR90 fibroblasts.
AB  - In contrast to rodent cells, normal human fibroblasts are generally resistant to
      neoplastic transformation in vitro. Here, we report the derivation and
      characterization of a spontaneously transformed cell line from normal human IMR90
      fibroblasts transduced with E1A and Ras oncogenes. Unlike the parental, non
      tumorigenic E1A/Ras-expressing IMR90 cells, these spontaneously transformed cells
      displayed aberrant growth potential in vitro and were capable of tumorigenesis in
      vivo. In contrast to the parental E1A/Ras-expressing cells, both the
      spontaneously transformed cells and cells derived from resultant tumors displayed
      specific t(7q;8q) and t(5q;17) structural chromosomal changes. Chromosome 8q
      contains c-Myc, which is capable of activating the telomerase catalytic subunit
      hTERT. Notably, upregulation of c-Myc, hTERT and telomerase activity were
      detected only in the tumorigenic cells. Transduction of Myc siRNA into the
      tumorigenic cells led to a concomitant downregulation of hTERT. Furthermore,
      transduction of Myc or hTERT into the non-tumorigenic E1A/Ras-expressing IMR90
      cells was able to confer tumorigenesis on these cells. These studies suggest that
      the t(7;8) translocation may result in Myc overexpression and its subsequent
      activation of hTERT, which may contribute to the tumorigenicity of the IMR90
      cells. Furthermore, this report describes additional successful neoplastic
      transformation of human IMR90 fibroblasts by defined genetic elements. The
      spontaneously transformed cells we have derived provide a valuable model system
      for the study of neoplastic transformation.

PMID- 16280333
TI  - Obesity - an epidemic of the twenty-first century: an update for psychiatrists.
AB  - Obesity is a chronic relapsing condition associated with significant morbidity
      and premature mortality. The prevalence of obesity has increased dramatically
      over the last 20 years and continues to do so, primarily as a result of changes
      in dietary intake and exercise patterns. There are considerable challenges
      associated with the management of the obesity epidemic involving both public
      health policies and individual treatment. Management of the obese individual
      involves lifelong lifestyle change for all, drugs for some, and surgery for a
      few. Appropriate selection of patients and the setting of realistic goals are
      crucial to the success of any weight-reducing programme. The aim of obesity
      management is to reduce associated morbidity and mortality, not necessarily to
      restore normal body weight. While the current trends in obesity are depressing, a
      better understanding of the pathophysiology and treatment of the condition should
      allow the clinician to be more optimistic for the future.

PMID- 16280334
TI  - Weight change with atypical antipsychotics in the treatment of schizophrenia.
AB  - Weight gain is a common complication of antipsychotic treatment. Its consequences
      include decreased self-esteem, reduced quality of life, reduced adherence with
      medication and increased morbidity and mortality. Most studies that assess weight
      change are short term. Among the atypicals mean weight gain is greatest with
      olanzapine and clozapine and least with aripiprazole and ziprasidone. Mean weight
      change obscures the marked individual variation in weight change that occurs
      during antipsychotic treatment i.e. irrespective of the antipsychotic, some
      subjects lose weight, some maintain their weight and some gain weight. In several
      long-term naturalistic studies (>6 months) mean weight gain is less marked than
      in randomised controlled trials of a shorter or comparable duration. This may
      reflect selective prescribing, the effect of weight management interventions and
      differences in the statistical analysis employed. With most antipsychotics weight
      stabilizes in the short to medium term but with clozapine it may continue beyond
      the first year. With some drugs clinical improvement is associated with short
      term weight gain. Predictors of long-term weight gain include lower body mass
      index, increased appetite and rapid initial weight increase. Weight gain is
      greater in first onset patients due to the lack of prior antipsychotic exposure
      and associated weight gain. The potential for weight gain should be discussed
      with patients before starting antipsychotic treatment and weight monitored
      regularly during treatment. It may be possible to predict weight gain before an
      antipsychotic is started or early on in treatment enabling high-risk patients to
      receive more intensive strategies to reduce weight gain.

PMID- 16280335
TI  - The role of lifestyle interventions and weight management in schizophrenia.
AB  - The recognition that schizophrenia is associated with metabolic comorbidity and a
      subsequent greater risk of cardiovascular events compared to the general
      population has led to attempts to reduce this metabolic burden. Increased weight,
      and smoking rates combined with less exercise and poor dietary choices, have led
      to a variety of behavioural programmes and pharmacological agents being evaluated
      with the aim of improving lifestyle and managing weight. Adjunctive
      pharmacological strategies for weight management have not been shown to be
      consistently effective and remain contraindicated in many schizophrenia subjects.
      However some novel compounds with recent promising data suggest that research
      should not be abandoned. In contrast a variety of behavioural interventions have
      shown a consistent degree of success not only with weight management but also in
      achieving lifestyle changes. Many reported data-sets are naturalistic or open
      label indicating that there is a difficulty in performing traditional randomized
      controlled studies in this area. The long-term naturalistic studies and holistic
      approaches show that weight management and significant lifestyle changes are
      attainable goals in schizophrenia patients. Weight management and lifestyle
      advice should be routinely offered to all schizophrenia subjects.

PMID- 16280336
TI  - An overview of the central control of weight regulation and the effect of
      antipsychotic medication.
AB  - Weight regulation is a complex system necessary for maintaining health. Obesity
      and cachexia are consequences of dysregulation and cause significant physical
      morbidity and mortality. In the developed world, obesity is a growing epidemic. A
      greater understanding of the neuroanatomy of weight regulation has been gained
      through advances in imaging and neural mapping techniques. The neural connections
      between key hypothalamic and other central nuclei have been elucidated. Advances
      in molecular biology have led to the identification and cloning of important
      peripheral and central weight regulating peptides. Weight gain as a consequence
      of antipsychotic use is increasingly being recognized as a serious clinical
      issue. The weight regulation system provides a framework upon which
      antipsychotics exert their weight-inducing effects. Some studies have sought,
      with inconsistent results, to establish associations between antipsychotic use
      and levels of weight regulating mediators. The receptor pharmacology of
      antipsychotics known to increase weight can be studied with a view to
      establishing genetic variants contributing to the risk. To date, the 5-HT(2C)
      receptor 759C/T polymorphism shows most promise. Further studies are required to
      replicate previous findings and establish new associations.

PMID- 16280337
TI  - Clustering of metabolic comorbidity in schizophrenia: a genetic contribution?
AB  - People with schizophrenia are more likely to develop type 2 diabetes than the
      general population. Although an increased risk of diabetes has been attributed to
      environmental determinants such as diet, lifestyle and antipsychotic drugs, the
      association between these two disorders was noticed well before the advent of
      current lifestyles and pharmacological interventions, raising the possibility of
      a shared genetic basis. Schizophrenia and type 2 diabetes are common diseases
      with a complex mode of inheritance which includes both genetic factors and
      environmental determinants. As susceptibility genes for both type 2 diabetes and
      schizophrenia are beginning to be identified there is increasing interest in the
      possibility of shared susceptibility loci between the two conditions. This
      article reviews the genetic basis to schizophrenia and type 2 diabetes and
      discusses the potential for shared loci between both conditions.

PMID- 16280338
TI  - Diabetes and schizophrenia 2005: are we any closer to understanding the link?
AB  - The association between schizophrenia and diabetes has been recognized for well
      over a century, but the underlying reasons for this association are unclear. In
      October 2003, an international group of diabetologists and psychiatrists met to
      review the literature relating to the association, and to create pragmatic
      guidelines for the management of diabetic risk in patients with severe mental
      illness. Since that meeting, over 100 additional papers have been published on
      the association between glucose abnormalities and schizophrenia, and this is a
      clear reflection of the level of interest in this clinically important area.
      Diabetes is highly prevalent among the schizophrenia population, but most
      sufferers remain undiagnosed in the community. The reasons why individuals with
      schizophrenia are more prone to developing diabetes than the general population
      are poorly defined, but likely to be multifactorial. The role of antipsychotic
      medications in the development of diabetes and other pre-diabetic states remains
      controversial, but it appears that the attributable risk is low. Traditional risk
      factors most probably account for much of the diabetes seen in schizophrenia
      populations, suggesting that routine screening and aggressive risk factor
      management are especially important in this patient group.

PMID- 16280339
TI  - Lipids for psychiatrists - an overview.
AB  - Serum cholesterol is a major risk factor for cardiovascular disease. Total
      cholesterol, LDL cholesterol and triglycerides are positively related to
      cardiovascular disease, while HDL cholesterol has an inverse relationship.
      Measurement of lipids is essential in individuals with established cardiovascular
      disease or type 2 diabetes, and may also be carried out in healthy individuals as
      part of cardiovascular risk assessment. Lifestyle measures are important in
      cardiovascular disease prevention, but the mainstay of lipid lowering therapy is
      appropriate use of lipid lowering drugs. Total and LDL cholesterol are the
      primary targets for treatment, but consideration should also be given to raising
      HDL cholesterol and lowering triglycerides where appropriate. Statins are the
      most frequently used lipid lowering agents, but there is an important place for
      other drugs, including ezetimibe, fibrates and nicotinic acid.

PMID- 16280340
TI  - The potential impact of antipsychotics on lipids in schizophrenia: is there
      enough evidence to confirm a link?
AB  - Lipid abnormalities are common in the general population and early data suggests
      that they may be more common in people with schizophrenia. Little data exist from
      treatment-naive patients making it difficult to differentiate any genetic
      contribution associated with a diagnosis of schizophrenia from the lifestyle
      risks associated with this diagnosis. Additional potential risks associated with
      antipsychotic drug treatment have been noted in the literature since 1971. The
      majority of the existing data on lipids derive from retrospective and cross
      sectional analyses of datasets that have been designed for other purposes.
      Specifically screening bias for lipid testing and treatment selection bias are
      important potential confounders. Prospective clinical trials are difficult to
      interpret, as many are short-term, report on non-fasting data and were never
      designed to evaluate the differential effects of antipsychotic drugs on lipids as
      a primary endpoint. There is little reported data on lipid fractions such as LDL
      and HDL. Nevertheless there is some evidence from placebo-controlled studies that
      antipsychotics may be differentially associated with a small, clinically
      insignificant increase in cholesterol and a larger, potentially clinically
      significant increase in triglycerides. Further prospective randomized trials,
      using fasting data and controlling for established risk factors such as diet and
      exercise are essential to determine if there are clinically meaningful
      differential effects on lipids associated with individual antipsychotic drugs.

PMID- 16280341
TI  - Metabolic syndrome and cardiovascular disease.
AB  - Metabolic syndrome is a constellation of clinical findings that identify
      individuals at higher than normal risk of developing diabetes mellitus or
      cardiovascular disease. There are two principal definitions, one emerging from
      the American National Cholesterol Education Program Expert Panel on Detection,
      Evaluation, and Treatment of High Blood Cholesterol in Adults, and the other from
      the World Health Organization. Both definitions share the common elements of
      abdominal obesity, hypertriglyceridaemia, low HDL-cholesterol, hypertension and
      abnormal glucose regulation. The syndrome is relatively common across continents,
      and also among those without marked obesity. It is even more common among
      patients with major mental health disorders such as schizophrenia. Metabolic
      syndrome can be used to assess risk for cardiovascular disorder and death, and is
      an alternative to Framingham Risk Calculations. C-reactive protein may play an
      additional role in risk prediction. Ongoing monitoring for all components of the
      metabolic syndrome is necessary. Individuals at high risk require multimodal
      interventions, including lifestyle interventions and targeted medications as
      appropriate.

PMID- 16280342
TI  - Metabolism, lifestyle and bipolar affective disorder.
AB  - Lifestyle, illness and treatment factors in people with bipolar disorder (BD) may
      confer additional risk of morbidity and mortality to the increasing rates of
      obesity, metabolic syndrome, diabetes mellitus and cardiovascular mortality in
      the general population.The aim of this review is to examine whether the risk of
      obesity and related morbidity and mortality are raised in BD, and possible
      contributory effects of lifestyle, illness and treatment factors to this
      risk.Systematic search of Medline and Cochrane Collaboration for relevant studies
      followed by a critical review of literature was carried out.Mortality from
      cardiovascular causes and pulmonary embolism (standardized mortality ratio
      approximately 2.0), and morbidity from obesity and type 2 diabetes mellitus may
      be increased in BD compared to the general population. Reduced exercise and poor
      diet, frequent depressive episodes, comorbidity with substance misuse and poor
      quality general medical care contribute to the additional risk of these medical
      problems in people with BD. There is no evidence that patients with BD are more
      sensitive than other patients to weight gain and medical problems associated with
      long-term use of psychotropic medication; in fact long-term treatment with
      lithium, antipsychotics and tricyclic antidepressants may reduce overall
      mortality. Psychiatrists, general practitioners and other health professionals
      should work together to systematically assess and manage weight gain and related
      medical problems to reduce the morbidity and mortality associated with obesity in
      BD. There is insufficient evidence to associate any of these factors with
      specific drug treatments. More research is required to understand how BD changes
      the risk for physical health comorbidity.

PMID- 16280344
TI  - Weight gain as a prognostic indicator of therapeutic improvement during acute
      treatment of schizophrenia with placebo or active antipsychotic.
AB  - Treatment-emergent weight gain may be a general marker of therapeutic
      improvement, even when improvements occur in the absence of active antipsychotic
      treatment. To investigate the association between treatment-emergent weight gain
      and therapeutic improvement across placebo and active treatments, and to examine
      the association between reported treatment-emergent weight changes and the
      treatments' reported efficacy. Data from a randomized, double-blind trial
      comparing treatment of schizophrenia with placebo and olanzapine were used to
      correlate weight change and change in psychopathology. Additionally, we
      correlated effect sizes of the efficacy of clozapine, olanzapine, risperidone,
      haloperidol and placebo (reported in meta-analytical reviews), with their
      reported weight changes. Weight gain significantly correlated with clinical
      improvements for placebo and olanzapine. The correlation between treatments'
      efficacy and corresponding weight changes was high (r 0.88, p 0.05). Treatment
      emergent weight gain appears to be an important marker of symptom reduction, and
      may not be exclusively attributable to pharmacological perturbations.

PMID- 16280343
TI  - Do guidelines for severe mental illness promote physical health and well-being?
AB  - The effective management of individuals with severe mental illnesses (SMIs)
      requires an holistic approach that offers reliable symptom control, but also
      addresses other clinical, emotional and social needs. The physical health of
      individuals with an SMI is often poor, with many being overweight or obese,
      having hypertension, diabetes or dyslipidaemia, and at significant risk of
      developing cardiovascular disease or other comorbidities. We have recently
      reviewed current UK and US guidelines for the management of individuals with
      schizophrenia and bipolar disorder, and found very different approaches to the
      holistic care of people with SMIs, especially in relation to the management of
      physical health and cardiovascular risk. UK guidelines acknowledge the high risk
      of physical morbidity and mortality in individuals with an SMI, but fail to
      address in detail the specifics of physical health monitoring and lifestyle
      management. US guidelines are more descriptive in terms of the type and extent of
      monitoring recommended, but there are inconsistencies between the guidelines
      produced by different organizations, and studies in the field suggest that none
      of them is being adequately implemented. Clear and consistent recommendations on
      how and when to monitor weight, cardiovascular function, and metabolic parameters
      and, importantly, what to do with the results, would support clinicians wishing
      to integrate physical and mental healthcare. Publication of specific
      recommendations on evidence-based physical health interventions that can work for
      people with SMIs would also help primary care and mental health services improve
      general well-being in their patients with severe mental illnesses.

PMID- 16280345
TI  - The effect of smoking on DNA effects in the comet assay: a meta-analysis.
AB  - The comet assay (alkaline single-cell gel electrophoresis, SCG or SCGE) is
      frequently used in biomonitoring to detect genotoxic effects in humans exposed at
      the workplace or in their environment. Because of its ready accessibility, blood
      is most frequently used in such studies. Many studies investigated cigarette
      smoking either as a genotoxic exposure itself or as a potential confounding
      factor in occupational studies. However, although smoking is considered to be a
      relevant exposure towards various genotoxins, conflicting results have been
      reported in the comet assay studies. The actual reasons for this discrepancy are
      not known. To further evaluate evidence for smoking-related DNA effects in the
      comet assay, we now used a meta-analysis approach based on a literature search.
      We identified 38 studies from 37 publications which were suited for a formal meta
      analysis based on the standardized mean difference (SMD) between the study
      groups. The evaluation of these 38 studies indicated higher levels of DNA damage
      in smokers than in non-smokers [under a random effects model, SMD = 0.55, 95%
      confidence interval = (0.16-0.93)]. Subdividing these studies into studies
      investigating the effect of smoking as a genotoxic exposure (Type A studies, n =
      12) and studies investigating smoking as a potential confounder in occupational
      studies (Type B, n = 26) indicated a significant difference only in Type A
      studies but not in Type B studies. Furthermore, studies using image analysis or
      image length measurements (n = 23) only indicated a tendency for a genotoxic
      effect of smoking, whereas studies using an arbitrary score (n = 15) found a
      significantly higher level of DNA damage in smokers.

PMID- 16280347
TI  - Breakdown of abdominal patterning in the Tribolium Kruppel mutant jaws.
AB  - During Drosophila segmentation, gap genes function as short-range gradients that
      determine the boundaries of pair-rule stripes. A classical example is Drosophila
      Kruppel (Dm'Kr) which is expressed in the middle of the syncytial blastoderm
      embryo. Patterning defects in Dm'Kr mutants are centred symmetrically around its
      bell-shaped expression profile. We have analysed the role of Kruppel in the short
      germ beetle Tribolium castaneum where the pair-rule stripes corresponding to the
      10 abdominal segments arise during growth stages subsequent to the blastoderm. We
      show that the previously described mutation jaws is an amorphic Tc'Kr allele.
      Pair-rule gene expression in the blastoderm is affected neither in the amorphic
      mutant nor in Tc'Kr RNAi embryos. Only during subsequent growth of the germ band
      does pair-rule patterning become disrupted. However, only segments arising
      posterior to the Tc'Kr expression domain are affected, i.e. the deletion profile
      is asymmetric relative to the expression domain. Moreover, stripe formation does
      not recover in posterior abdominal segments, i.e. the Tc'Kr(jaws) phenotype does
      not constitute a gap in segment formation but results from a breakdown of
      segmentation past the 5th eve stripe. Alteration of pair-rule gene expression in
      Tc'Kr(jaws) mutants does not suggest a direct role of Tc'Kr in defining specific
      stripe boundaries as in Drosophila. Together, these findings show that the
      segmentation function of Kruppel in this short-germ insect is fundamentally
      different from its role in the long-germ embryo of Drosophila. The role of Tc'Kr
      in Hox gene regulation, however, is in better accordance to the Drosophila
      paradigm.

PMID- 16280346
TI  - Normal myoblast fusion requires myoferlin.
AB  - Muscle growth occurs during embryonic development and continues in adult life as
      regeneration. During embryonic muscle growth and regeneration in mature muscle,
      singly nucleated myoblasts fuse to each other to form myotubes. In muscle growth,
      singly nucleated myoblasts can also fuse to existing large, syncytial myofibers
      as a mechanism of increasing muscle mass without increasing myofiber number.
      Myoblast fusion requires the alignment and fusion of two apposed lipid bilayers.
      The repair of muscle plasma membrane disruptions also relies on the fusion of two
      apposed lipid bilayers. The protein dysferlin, the product of the Limb Girdle
      Muscular Dystrophy type 2 locus, has been shown to be necessary for efficient,
      calcium-sensitive, membrane resealing. We now show that the related protein
      myoferlin is highly expressed in myoblasts undergoing fusion, and is expressed at
      the site of myoblasts fusing to myotubes. Like dysferlin, we found that myoferlin
      binds phospholipids in a calcium-sensitive manner that requires the first C2A
      domain. We generated mice with a null allele of myoferlin. Myoferlin null
      myoblasts undergo initial fusion events, but they form large myotubes less
      efficiently in vitro, consistent with a defect in a later stage of myogenesis. In
      vivo, myoferlin null mice have smaller muscles than controls do, and myoferlin
      null muscle lacks large diameter myofibers. Additionally, myoferlin null muscle
      does not regenerate as well as wild-type muscle does, and instead displays a
      dystrophic phenotype. These data support a role for myoferlin in the maturation
      of myotubes and the formation of large myotubes that arise from the fusion of
      myoblasts to multinucleate myotubes.

PMID- 16280348
TI  - Pelota controls self-renewal of germline stem cells by repressing a Bam
      independent differentiation pathway.
AB  - In the Drosophila ovary, germline stem cell (GSC) self-renewal is controlled by
      both extrinsic and intrinsic factors. The Bmp signal from niche cells controls
      GSC self-renewal by directly repressing a Bam-dependent differentiation pathway
      in GSCs. pelota (pelo), which has been previously shown to be required for
      Drosophila male meiosis, was identified in our genetic screen as a dominant
      suppressor of the dpp overexpression-induced GSC tumor phenotype. In this study,
      we reveal the unexpected new role of Pelo in controlling GSC self-renewal by
      repressing a Bam-independent differentiation pathway. In pelo mutant ovaries,
      GSCs are lost rapidly owing to differentiation. Results from genetic mosaic
      analysis and germ cell-specific rescue show that it functions as an intrinsic
      factor to control GSC self-renewal. In pelo mutant GSCs, Bmp signaling activity
      detected by Dad-lacZ expression is downregulated, but bam expression is still
      repressed. Furthermore, bam mutant germ cells are still able to differentiate
      into cystocytes without pelo function, indicating that Pelo is involved in
      repressing a Bam-independent differentiation pathway. Consistent with its
      homology to the eukaryotic translation release factor 1alpha, we show that Pelo
      is localized to the cytoplasm of the GSC. Therefore, Pelo controls GSC self
      renewal by repressing a Bam-independent differentiation pathway possibly through
      regulating translation. As Pelo is highly conserved from Drosophila to mammals,
      it may also be involved in the regulation of adult stem cell self-renewal in
      mammals, including humans.

PMID- 16280350
TI  - Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is
      differentially linked to CNS immune cell recruitment.
AB  - Understanding the mechanisms of immune cell migration to multiple sclerosis
      lesions offers significant therapeutic potential. This study focused on the
      chemokines CXCL12 (SDF-1) and CXCL13 (BCA-1), both of which regulate B cell
      migration in lymphoid tissues. We report that immunohistologically CXCL12 was
      constitutively expressed in CNS parenchyma on blood vessel walls. In both active
      and chronic inactive multiple sclerosis lesions CXCL12 protein was elevated and
      detected on astrocytes and blood vessels. Quantitative PCR demonstrated that
      CXCL13 was produced in actively demyelinating multiple sclerosis lesions, but not
      in chronic inactive lesions or in the CNS of subjects who had no neurological
      disease. CXCL13 protein was localized in perivascular infiltrates and scattered
      infiltrating cells in lesion parenchyma. In the CSF of relapsing-remitting
      multiple sclerosis patients, both CXCL12 and CXCL13 were elevated. CXCL13, but
      not CXCL12, levels correlated strongly with intrathecal immunoglobulin production
      as well as the presence of B cells, plasma blasts and T cells. About 20% of CSF
      CD4+ cells and almost all B cells expressed the CXCL13 receptor CXCR5. In vitro,
      CXCL13 was produced by monocytes and at much higher levels by macrophages. CXCL13
      mRNA and protein expression was induced by TNFalpha and IL-1beta but inhibited by
      IL-4 and IFNgamma. Together, CXCL12 and CXCL13 are elevated in active multiple
      sclerosis lesions and CXCL12 also in inactive lesions. The consequences of CXCL12
      up-regulation could be manifold. CXCL12 localization on blood vessels indicates a
      possible role in leucocyte extravasation, and CXCL12 may contribute to plasma
      cell persistence since its receptor CXCR4 is retained during plasma cell
      differentiation. CXCL12 may contribute to axonal damage as it can become a
      neurotoxic mediator of cleavage by metalloproteases, which are present in
      multiple sclerosis lesions. The strong linkage of CXCL13 to immune cells and
      immunoglobulin levels in CSF suggests that this is one of the factors that
      attract and maintain B and T cells in inflamed CNS lesions. Therefore, both
      CXCL13 and CXCR5 may be promising therapeutic targets in multiple sclerosis.

PMID- 16280351
TI  - Distinct right frontal lobe activation in language processing following left
      hemisphere injury.
AB  - Right hemisphere activation during functional imaging studies of language has
      frequently been reported following left hemisphere injury. Few studies have
      anatomically characterized the specific right hemisphere structures engaged. We
      used functional MRI (fMRI) with verbal fluency tasks in 12 right-handed patients
      with left temporal lobe epilepsy (LTLE) and 12 right-handed healthy controls to
      localize language-related activity in the right inferior frontal gyrus (RIFG).
      During the phonemic task, LTLE patients activated a significantly more posterior
      region of the right anterior insula/frontal operculum than healthy controls (P =
      0.02). Activation of the left inferior frontal gyrus (LIFG) did not differ
      significantly between the two groups. This suggests that, following left
      hemisphere injury, language-related processing in the right hemisphere differs
      from that with a functionally normal left hemisphere. The localization of
      activation in the left and right inferior frontal gyri was determined with
      respect to the anatomical sub-regions pars opercularis (Pop), pars triangularis
      (Ptr) and pars orbitalis (Por). In the LIFG, both healthy controls (8 out of 12)
      and LTLE patients (9 out of 12) engaged primarily Pop during phonemic fluency.
      Activations in the RIFG, however, were located mostly in the anterior
      insula/frontal operculum in both healthy controls (8 out of 12) and LTLE patients
      (8 out of 12), albeit in distinct regions. Mapping the locations of peak voxels
      in relation to previously obtained cytoarchitectonic maps of Broca's area
      confirmed lack of homology between activation regions in the left and right IFG.
      Verbal fluency-related activation in the RIFG was not anatomically homologous to
      LIFG activation in either patients or controls. To test more directly whether
      RIFG activation shifts in a potentially adaptive manner after left hemisphere
      injury, fMRI studies were performed in a patient prior to and following
      anatomical left hemispherectomy for the treatment of Rasmussen's encephalitis. An
      increase in activation magnitude and posterior shift in location were found in
      the RIFG after hemispherectomy for both phonemic and semantic tasks. Together,
      these results suggest that left temporal lobe injury is associated with
      potentially adaptive changes in right inferior frontal lobe functions in
      processing related to expressive language.

PMID- 16280349
TI  - Mis-specified cells die by an active gene-directed process, and inhibition of
      this death results in cell fate transformation in Drosophila.
AB  - Incorrectly specified or mis-specified cells often undergo cell death or are
      transformed to adopt a different cell fate during development. The underlying
      cause for this distinction is largely unknown. In many developmental mutants in
      Drosophila, large numbers of mis-specified cells die synchronously, providing a
      convenient model for analysis of this phenomenon. The maternal mutant bicoid is
      particularly useful model with which to address this issue because its mutant
      phenotype is a combination of both transformation of tissue (acron to telson) and
      cell death in the presumptive head and thorax regions. We show that a subset of
      these mis-specified cells die through an active gene-directed process involving
      transcriptional upregulation of the cell death inducer hid. Upregulation of hid
      also occurs in oskar mutants and other segmentation mutants. In hid bicoid double
      mutants, mis-specified cells in the presumptive head and thorax survive and
      continue to develop, but they are transformed to adopt a different cell fate. We
      provide evidence that the terminal torso signaling pathway protects the mis
      specified telson tissue in bicoid mutants from hid-induced cell death, whereas
      mis-specified cells in the head and thorax die, presumably because equivalent
      survival signals are lacking. These data support a model whereby mis
      specification can be tolerated if a survival pathway is provided, resulting in
      cellular transformation.

PMID- 16280352
TI  - Getting the measure of spasticity in multiple sclerosis: the Multiple Sclerosis
      Spasticity Scale (MSSS-88).
AB  - Spasticity is most commonly defined as an inappropriate, velocity dependent,
      increase in muscle tonic stretch reflexes, due to the amplified reactivity of
      motor segments to sensory input. It forms one component of the upper motor neuron
      syndrome and often leads to muscle stiffness and disability. Spasticity can,
      therefore, be measured through electrophysiological, biomechanical and clinical
      evaluation, the last most commonly using the Ashworth scale. None of these
      techniques incorporate the patient experience of spasticity, nor how it affects
      people's daily lives. Consequently, we set out to construct a rating scale to
      quantify the perspectives of the impact of spasticity on people with multiple
      sclerosis. Qualitative methods (in-depth patient interviews and focus groups,
      expert opinion and literature review) were used to develop a conceptual framework
      of spasticity impact, and to generate a pool of items with the potential to
      convert this framework into a rating scale with multiple dimensions. This item
      pool was administered, in the form of a questionnaire, to a sample of people with
      multiple sclerosis and spasticity. Guided by Rasch analysis, we constructed and
      validated a rating scale for each component of the conceptual framework.
      Decisions regarding item selection were based on the integration and assimilation
      of seven specific analyses including clinical meaning, ordering of thresholds,
      fit statistics and differential item functioning. The qualitative phase (17
      patient interviews, 3 focus groups) generated 144 potential scale items and a
      conceptual model with eight components addressing symptoms (muscle stiffness,
      pain and discomfort and muscle spasms,), physical impact (activities of daily
      living, walking and body movements) and psychosocial impact (emotional health,
      social functioning). The first postal survey was sent to 272 people with multiple
      sclerosis and had a response rate of 88%. Findings supported the development of
      scales for each component but demonstrated that five item response options were
      too many. The 144-item questionnaire, reformatted with four-item response
      options, was administered with four validating instruments to an independent
      sample of 259 people with multiple sclerosis (response rate 78%). From the
      responses, an 88-item instrument with eight subscales was developed that
      satisfied criteria for reliable and valid measurement. Correlations with other
      measures were consistent with predictions. The 88-item Multiple Sclerosis
      Spasticity Scale (MSSS-88) is a reliable and valid, patient-based, interval-level
      measure of the impact of spasticity in multiple sclerosis. It has the potential
      to advance outcomes measurement in clinical trials and clinical practice, and
      provides a new perspective in the clinical evaluation of spasticity.

PMID- 16280353
TI  - Silent event-related fMRI reveals deficient motor and enhanced somatosensory
      activation in orofacial dystonia.
AB  - Previous studies showed cortical dysfunction and impaired sensorimotor
      integration in primary generalized and focal hand dystonia. We used a whistling
      task and silent event-related fMRI to investigate functional changes in patients
      with blepharospasm and patients with a combination of blepharospasm and
      oromandibular dystonia (Meige's syndrome). Whistling served as a model for a
      skilful orofacial movement with a high demand on sensorimotor integration. It
      allowed us to study the oromandibular motor system that is clinically affected in
      Meige's syndrome but not in isolated blepharospasm. In Meige's syndrome,
      functional MRI revealed deficient activation of the primary motor and ventral
      premotor cortex within the mouth representation area during whistling. Compared
      with healthy controls, both forms of orofacial dystonia had increased activation
      of bilateral somatosensory areas and the caudal supplementary motor area (SMA) in
      common. While overactivity of somatosensory areas and caudal SMA in Meige
      patients was partly reversed by botulinum toxin treatment, impaired motor
      activation was not. We conclude that impaired motor activation appears to be
      specific for the clinically affected oromandibular motor system in Meige's
      syndrome while enhanced somatosensory activation is a common abnormality in both
      forms of orofacial dystonia independent of the affected motor system.
      Somatosensory overactivity indicates an altered somatosensory representation in
      orofacial dystonia while impaired motor activation may be a functional correlate
      of reduced cortical inhibition during oromandibular motor execution in Meige's
      syndrome.

PMID- 16280354
TI  - Capture by misleading information and its false acceptance in patients with
      traumatic brain injury.
AB  - Exposure to misleading information, presented after a critical episode, can alter
      or impair memory reports about that episode. Here, we examine vulnerability to
      misleading information in patients with traumatic brain injury (TBI). The ability
      to initiate an effective retrieval strategy and inhibit irrelevant or interfering
      information requires participation from the prefrontal cortices, which are
      susceptible to damage following brain injury. We report that TBI patients are
      more prone to interference effects produced by misleading information during a
      cued-recall task and are more likely to accept this information as the product of
      'remembering' compared with healthy controls. The results are consistent with a
      model proposing that patients are captured by highly accessible responses
      eliminating their opportunity to engage in recollection. Correlations between the
      cued-recall interference task and other executive measures helped elucidate the
      processes underlying 'capture'. In TBI patients, reduced recollection produced by
      a misleading prime was associated with impaired prospective remembering when
      engaged in a background task. A common functional deficit that may underlie poor
      performance on both tasks is the failure to inhibit previously relevant but
      currently irrelevant information. Subjective reports pertaining to the subject's
      cued-recall response were indexed by electrodermal activity. In control subjects,
      larger skin conductance responses (SCRs) were associated with a greater frequency
      of guess reports, suggesting that SCRs provide a marker for uncertainty regarding
      the candidacy of a selected response. TBI patients did not show this
      relationship, suggesting that impairments of post-retrieval evaluation might also
      underlie greater false acceptance of misinformation. Discussion focuses on the
      role of the prefrontal cortex and cognitive processes that mediate the selection
      and evaluation of memories.

PMID- 16280355
TI  - Advances in the management of endometriosis: an update for clinicians.
AB  - Endometriosis is a chronic and recurrent disease characterized by the presence
      and proliferation of endometrial tissue outside the uterine cavity, which occurs
      in approximately 10% of women of reproductive age. In this estrogen-dependent
      disorder, lesions become inactive and gradually undergo regression during states
      of ovarian down-regulation, such as amenorrhoea or menopause. The impact of
      endometriosis includes impaired fertility potential, as well as symptoms of
      dysmenorrhoea, dyspareunia and chronic non-menstrual pain, all of which adversely
      affect quality of life. Management of endometriosis focuses on pain relief and
      includes medical and surgical treatment. Pharmacologic therapies currently in use
      include combination oral contraceptives (COCs), danazol, GnRH analogues and
      progestins. Although some agents show efficacy in relieving pain, all differ in
      their side effects, making it difficult to achieve a balance between efficacy and
      safety. Efficacy has been demonstrated with danazol or GnRH analogues; however,
      treatment is limited to 6 months because of significant metabolic side effects.
      Alternatives for longer-term management of symptoms include add-back therapy with
      GnRH analogues, COCs or progestins. Newer options for treatment of endometriosis
      include depot medroxyprogesterone acetate subcutaneous injection, as well as
      several agents under investigation that may prove to have therapeutic potential.

PMID- 16280356
TI  - HLA-G in human reproduction: aspects of genetics, function and pregnancy
      complications.
AB  - The non-classical human leukocyte antigen (HLA) class Ib genes, HLA-E, -G and -F,
      are located on chromosome 6 in the human major histocompatibility complex (MHC).
      HLA class Ib antigens resemble the HLA class Ia antigens in many ways, but
      several major differences have been described. This review will, in particular,
      discuss HLA-G and its role in human reproduction and in the human MHC. HLA-G
      seems to be important in the modulation of the maternal immune system during
      pregnancy and thereby the maternal acceptance of the semiallogenic fetus. Recent
      findings regarding aspects of HLA-G polymorphism, the possible significance of
      this polymorphism in respect to HLA-G function and certain complications of
      pregnancy (such as pre-eclampsia and recurrent spontaneous abortions (RSA)) are
      discussed together with possible importance to IVF. Finally, aspects of a
      possible role of HLA-G in organ transplantation and in inflammatory or autoimmune
      disease, and of HLA-G in an evolutionary context, are also briefly examined.

PMID- 16280358
TI  - Granule-mediated killing by granzyme B and perforin requires a mannose 6
      phosphate receptor and is augmented by cell surface heparan sulfate.
AB  - During granule-mediated killing by cytotoxic T lymphocytes or natural killer
      cells, the serine protease granzyme B enters the target cell by endocytosis and
      induces apoptosis. Previous studies suggested a role for the mannose 6-phosphate
      receptor, but further experiments with purified granzyme B indicated this was not
      essential. Additionally, it is now clear that grB is exocytosed from killer cells
      in a high-molecular-weight complex with the proteoglycan serglycin. Here granzyme
      B was delivered as a purified monomer, or in complex with either
      glycosaminoglycans or serglycin, and killing was evaluated. When granzyme B was a
      monomer, soluble mannose 6-phosphate had a limited impact, whereas apoptosis
      induced by the complexed grB was effectively inhibited by mannose 6-phosphate.
      Most importantly, when granzyme B and perforin were delivered together from
      granules, inhibition by mannose 6-phosphate was also observed. In pulldown assays
      mediated by the cation-independent mannose 6-phosphate receptor, granzyme B bound
      to the receptor more intensely in the presence of immobilized heparan sulfate. We
      therefore propose the model that under physiological conditions serglycin-bound
      granzyme B is critically endocytosed by a mannose 6-phosphate receptor, and
      receptor binding is enhanced by cell surface heparan sulfate.

PMID- 16280357
TI  - Regulation of histone deacetylase 4 expression by the SP family of transcription
      factors.
AB  - Histone deacetylases mediate critical cellular functions but relatively little is
      known about mechanisms controlling their expression, including expression of
      HDAC4, a class II HDAC implicated in the modulation of cellular differentiation
      and viability. Endogenous HDAC4 mRNA, protein levels and promoter activity were
      all readily repressed by mithramycin, suggesting regulation by GC-rich DNA
      sequences. We validated consensus binding sites for Sp1/Sp3 transcription factors
      in the HDAC4 promoter through truncation studies and targeted mutagenesis.
      Specific and functional binding by Sp1/Sp3 at these sites was confirmed with
      chromatin immunoprecipitation (ChIP) and electromobility shift assays (EMSA).
      Cotransfection of either Sp1 or Sp3 with a reporter driven by the HDAC4 promoter
      led to high activities in SL2 insect cells (which lack endogenous Sp1/Sp3). In
      human cells, restored expression of Sp1 and Sp3 up-regulated HDAC4 protein
      levels, whereas levels were decreased by RNA-interference-mediated knockdown of
      either protein. Finally, variable levels of Sp1 were in concordance with that of
      HDAC4 in a number of human tissues and cancer cell lines. These studies together
      characterize for the first time the activity of the HDAC4 promoter, through which
      Sp1 and Sp3 modulates expression of HDAC4 and which may contribute to tissue or
      cell-line-specific expression of HDAC4.

PMID- 16280359
TI  - Chk1 and p21 cooperate to prevent apoptosis during DNA replication fork stress.
AB  - Cells respond to DNA replication stress by triggering cell cycle checkpoints,
      repair, or death. To understand the role of the DNA damage response pathways in
      determining whether cells survive replication stress or become committed to
      death, we examined the effect of loss of these pathways on cellular response to
      agents that slow or arrest DNA synthesis. We show that replication inhibitors
      such as excess thymidine, hydroxyurea, and camptothecin are normally poor
      inducers of apoptosis. However, these agents become potent inducers of death in S
      phase cells upon small interfering RNA-mediated depletion of the checkpoint
      kinase Chk1. This death response is independent of p53 and Chk2. p21-deficient
      cells, on the other hand, produce a more robust apoptotic response upon Chk1
      depletion. p21 is normally induced only late after thymidine treatment. In Chk1
      depleted cells p21 induction occurs earlier and does not require p53. Thus, Chk1
      plays a primary role in the protection of cells from death induced by replication
      fork stress, whereas p21 mediates through its role in regulating entry into S
      phase. These findings are of potential importance to cancer therapy because we
      demonstrate that the efficacy of clinically relevant agents can be enhanced by
      manipulation of these signaling pathways.

PMID- 16280360
TI  - An effector domain mutant of Arf6 implicates phospholipase D in endosomal
      membrane recycling.
AB  - In this study, we investigated the role of phospholipase D (PLD) in mediating
      Arf6 function in cells. Expression of Arf6 mutants that are defective in
      activating PLD, Arf6N48R and Arf6N48I, inhibited membrane recycling to the plasma
      membrane (PM), resulting in an accumulation of tubular endosomal membranes.
      Additionally, unlike wild-type Arf6, neither Arf6 mutant could generate
      protrusions or recruit the Arf6 GTPase activating protein (GAP) ACAP1 onto the
      endosome in the presence of aluminum fluoride. Remarkably, all of these
      phenotypes, including accumulated tubular endosomes, blocked recycling, and
      failure to make protrusions and recruit ACAP effectively, could be recreated in
      either untransfected cells or cells expressing wild-type Arf6 by treatment with 1
      butanol to inhibit the formation of phosphatidic acid (PA), the product of PLD.
      Moreover, most of the defects present in cells expressing Arf6N48R or N48I could
      be reversed by treatment with agents expected to elevate PA levels in cells.
      Together, these observations provide compelling evidence that Arf6 stimulation of
      PLD is required for endosomal membrane recycling and GAP recruitment.

PMID- 16280361
TI  - Nonclassical action of retinoic acid on the activation of the cAMP response
      element-binding protein in normal human bronchial epithelial cells.
AB  - Vitamin A (retinol) is essential for normal regulation of cell growth and
      differentiation. We have shown that the retinol metabolite retinoic acid (RA)
      induces mucous cell differentiation of normal human tracheobronchial epithelial
      (NHTBE) cells. However, early biological effects of RA in the differentiation of
      bronchial epithelia are largely unknown. Here, we showed that RA rapidly
      activated cAMP response element-binding protein (CREB). However, RA did not use
      the conventional retinoic acid receptor (RAR)/retinoid X receptor (RXR) to
      activate CREB. RA activated CREB in NHTBE and H1734 cells in which RARs/RXR were
      silenced with small interfering RNA (siRNA) targeting RAR/RXR expression or
      deactivated by antagonist. Inhibition of protein kinase C (PKC) or extracellular
      regulated kinase (ERK1/2) blocked the RA-mediated activation of CREB. In
      addition, depletion of p90 ribosomal S6 kinase (RSK) via siRSK1/2 completely
      abolished the activation, suggesting that PKC, ERK, and RSK are required for the
      activation. Altogether, this study provides the first evidence that RA rapidly
      activates CREB transcription factor via PKC, ERK, and RSK in a retinoid receptor
      independent manner in normal bronchial epithelial cells. This noncanonical RA
      signaling pathway may play an important role in mediating early biological
      effects in the mucociliary differentiation of bronchial epithelia.

PMID- 16280362
TI  - Proteolysis of cortactin by calpain regulates membrane protrusion during cell
      migration.
AB  - Calpain 2 regulates membrane protrusion during cell migration. However, relevant
      substrates that mediate the effects of calpain on protrusion have not been
      identified. One potential candidate substrate is the actin binding protein
      cortactin. Cortactin is a Src substrate that drives actin polymerization by
      activating the Arp2/3 complex and also stabilizes the cortical actin network. We
      now provide evidence that proteolysis of cortactin by calpain 2 regulates
      membrane protrusion dynamics during cell migration. We show that cortactin is a
      calpain 2 substrate in fibroblasts and that the preferred cleavage site occurs in
      a region between the actin binding repeats and the alpha-helical domain. We have
      generated a mutant cortactin that is resistant to calpain proteolysis but retains
      other biochemical properties of cortactin. Expression of the calpain-resistant
      cortactin, but not wild-type cortactin, impairs cell migration and increases
      transient membrane protrusion, suggesting that calpain proteolysis of cortactin
      limits membrane protrusions and regulates migration in fibroblasts. Furthermore,
      the enhanced protrusion observed with the calpain-resistant cortactin requires
      both the Arp2/3 binding site and the Src homology 3 domain of cortactin.
      Together, these findings suggest a novel role for calpain-mediated proteolysis of
      cortactin in regulating membrane protrusion dynamics during cell migration.

PMID- 16280363
TI  - The inositol polyphosphate 5-phosphatase, PIPP, Is a novel regulator of
      phosphoinositide 3-kinase-dependent neurite elongation.
AB  - The spatial activation of phosphoinositide 3-kinase (PI3-kinase) signaling at the
      axon growth cone generates phosphatidylinositol 3,4,5 trisphosphate
      (PtdIns(3,4,5)P3), which localizes and facilitates Akt activation and stimulates
      GSK-3beta inactivation, promoting microtubule polymerization and axon elongation.
      However, the molecular mechanisms that govern the spatial down-regulation of
      PtdIns(3,4,5)P3 signaling at the growth cone remain undetermined. The inositol
      polyphosphate 5-phosphatases (5-phosphatase) hydrolyze the 5-position phosphate
      from phosphatidylinositol 4,5 bisphosphate (PtdIns(4,5)P2) and/or
      PtdIns(3,4,5)P3. We demonstrate here that PIPP, an uncharacterized 5-phosphatase,
      hydrolyzes PtdIns(3,4,5)P3 forming PtdIns(3,4)P2, decreasing Ser473-Akt
      phosphorylation. PIPP is expressed in PC12 cells, localizing to the plasma
      membrane of undifferentiated cells and the neurite shaft and growth cone of NGF
      differentiated neurites. Overexpression of wild-type, but not catalytically
      inactive PIPP, in PC12 cells inhibited neurite elongation. Targeted depletion of
      PIPP using RNA interference (RNAi) resulted in enhanced neurite differentiation,
      associated with neurite hyperelongation. Inhibition of PI3-kinase activity
      prevented neurite hyperelongation in PIPP-deficient cells. PIPP targeted
      depletion resulted in increased phospho-Ser473-Akt and phospho-Ser9-GSK-3beta,
      specifically at the neurite growth cone, and accumulation of PtdIns(3,4,5)P3 at
      this site, associated with enhanced microtubule polymerization in the neurite
      shaft. PIPP therefore inhibits PI3-kinase-dependent neurite elongation in PC12
      cells, via regulation of the spatial distribution of phospho-Ser473-Akt and
      phospho-Ser9-GSK-3beta signaling.

PMID- 16280364
TI  - Molecular mechanism of cell-autonomous circadian gene expression of Period2, a
      crucial regulator of the mammalian circadian clock.
AB  - Although circadian transcription of Period2 (Per2) is fundamental for the
      generation of circadian rhythm, the molecular mechanism remains unclear. Here we
      report that cell-autonomous circadian transcription of Per2 is driven by two
      transcriptional elements, one for rhythm generation and the other for phase
      control. The former contains the E-box-like sequence (CACGTT) that is sufficient
      and indispensable to drive oscillation, and indeed circadian transcription
      factors site-specifically bind to it. Furthermore, the nature of this atypical E
      box is different from that of the classical circadian E-box. The current feedback
      loop model is based mainly on Period1. Our results provide not only compelling
      evidence in support of this model but also an explanation for a general basic
      mechanism to produce various patterns in the phase and amplitude of cell
      autonomous circadian gene expression.

PMID- 16280365
TI  - IL-4 inhibits calcium transients in bovine trachealis cells by a ryanodine
      receptor-dependent mechanism.
AB  - IL-4 and IL-13 have important roles in the pathogenesis of asthma. A novel
      finding was that brief exposure of airway smooth muscle cells to IL-4 inhibited
      carbachol-stimulated calcium transients. We hypothesized that IL-4 inhibits
      transients by decreasing calcium store content and tested this by measuring the
      effects of IL-4 on transients induced by a nonspecific ionophore. Bovine
      trachealis cells were loaded with fura 2-AM, and cytosolic calcium concentrations
      ([Ca2+]i) were measured in single cells by digital microscopy. Stimulation (S1)
      with carbachol (10 microM) caused rapid, transient increases in [Ca2+]i to 1299
      +/- 355 nM (n=5). After recovery of calcium stores, stimulation (S2) of the same
      cells with ionomycin (10 microM), in the absence of extracellular calcium, also
      increased [Ca2+]i to give S2/S1 ratio of 1.03 +/- 0.29. However, after 20 min of
      IL-4 (50 ng/ml), but not IL-13, ionomycin transients were decreased to 0.50 +/-
      0.16 (S2/S1, P=0.02, n=6). IL-4 did not inhibit transients with ryanodine
      receptor calcium release channels (RyR) blocked by ryanodine (200 microM)
      (S2/S1=1.01+/-0.11) but still did in the presence of 8-bromo cyclic ADP-ribose,
      an antagonist of cyclic ADP-ribose (cADPR) signaling at RyR (S2/S1=0.48+/-0.13).
      Together, findings suggest that IL-4 decreases intracellular calcium stores by
      mechanisms dependent on RyR, but not on cADPR signaling.

PMID- 16280366
TI  - Immunomodulatory impact of the A2A adenosine receptor on the profile of
      chemokines produced by neutrophils.
AB  - In LPS-stimulated human neutrophils, engagement of the adenosine A2A receptor
      selectively prevented the expression and release of TNF-alpha, MIP-1alpha/CCL3,
      MIP-1beta/CCL4, MIP-2alpha/CXCL2, and MIP-3alpha/CCL20. In mice lacking the A2A
      receptor, granulocytes that migrated into the air pouch 4 h after LPS injection
      expressed higher mRNA levels of TNF-alpha, MIP-1alpha, and MIP-1beta than PMNs
      from wild-type mice. In mononuclear cells present in the air pouch 72 h after LPS
      injection, expression of IL-1beta, TNF-alpha, IL-6, and MCP-2/CCL6 was higher in
      A2AR knockout mice. In addition to highlighting neutrophils as an early and
      pivotal target for mediating adenosine anti-inflammatory activities, these
      results identify TNF-alpha and the MIP chemokine family as gene products whose
      expression is pivotally affected by activation of A2AR in LPS-activated PMNs.
      Modulation by A2AR in the production of inflammatory signals by PMNs may thus
      influence the evolution of an inflammatory response by reducing the activation
      status of inflammatory cells.

PMID- 16280367
TI  - Congenital structural anomalies in offspring of women with epilepsy--a population
      based cohort study in Finland.
AB  - BACKGROUND: Offspring of women with epilepsy may have an increased risk for
      congenital malformations, probably attributable to maternal antiepileptic
      medication. We conducted this population-based study to obtain valid and accurate
      estimates on major congenital malformations in the offspring of women with
      epilepsy, based on a large and representative patient cohort. METHODS: We
      identified all women (n = 6,535) entitled to full reimbursement for antiepileptic
      medication indicated for epilepsy for the first time between 1985 and 1994 from
      the Social Insurance Institution of Finland database. A reference cohort (n =
      14,704) was identified from the Finnish Population Register Centre. Information
      on children born between 1993 and 2000 (patient cohort, n = 2,162; reference
      cohort, n = 5,413) was obtained from the Medical Birth Register. Information on
      children born with malformation (patient cohort, n = 116; reference cohort, n =
      151) was obtained from the Finnish Register of Congenital Malformations. RESULTS:
      The prevalence of major malformation was 54/1,000 births among patients with
      epilepsy and 28/1,000 births among mothers without epilepsy, corresponding to a 2
      fold overall risk for malformation in the offspring of women with epilepsy. The
      risk for spina bifida [odds ratio (OR) = 11.3, 95% confidence interval (CI) 2.34
      108] and congenital anomalies of genital organs (OR = 8.38, 95% CI 2.15-47.4) was
      substantially elevated in the offspring of mothers with epilepsy. CONCLUSIONS:
      The absolute excess in the prevalence of major malformations was 26/1,000 births
      in the offspring of mothers with epilepsy in relation to the offspring of
      reference mothers. The highest relative risk was observed in spina bifida and
      congenital anomalies of genital organs. However, these malformations cover only a
      small proportion of all major malformations.

PMID- 16280368
TI  - Decline in, and lack of difference between, average birth weights among African
      and Portuguese babies in Portugal.
AB  - BACKGROUND: In preliminary data in Portugal, we found that African babies of
      migrant mothers were heavier than White Portuguese babies born in Lisbon. We
      investigate whether this pattern is replicated in the national data, and in
      addition the trends in birth weight in these groups. METHODS:  DESIGN AND
      SETTING: Births registered between 1995 and 2002 classified by reported
      nationality of mothers. PARTICIPANTS: 849,595 Portuguese births ('Portuguese'
      nationality, predominantly of European descent) and 22,463 African births
      ('Angola', 'Cape Verde', or 'Guinea Bissau, Republic of Guinea or Equatorial
      Guinea' nationality, predominantly of African origin). RESULTS: Among Portuguese
      births, there was a decline in births to teenaged mothers and an increase to
      mothers aged >or=35 years, with >9 years of education or in a non-manual class,
      but among African births there was an increase in births to teenaged mothers and
      a decline to mothers from advantaged socioeconomic backgrounds. Using the Wilcox
      Russell method, overall mean birth weights of term Portuguese (3,303, SD 424 g)
      and African (3297, SD 441 g) babies were not different but the percentage of
      small preterm births was higher among African (4.7%) than among Portuguese (2.9%)
      births. Between 1995 and 2002, mean birth weight of term Portuguese babies
      declined by 58 g (3,334-3,276 g) and of African babies by 57 g (3,341-3,284 g).
      The left shift of the birth weight distributions was independent of maternal age,
      parity, and social factors among Portuguese babies, but among African babies the
      decrease appeared to be associated with socioeconomic advantage. CONCLUSION:
      There has been a downward trend in birth weights in Portugal among both
      Portuguese and African term births, but average birth weights of the two groups
      were similar.

PMID- 16280369
TI  - Conversion from calcineurin inhibitors to sirolimus in chronic allograft
      dysfunction: changes in glomerular haemodynamics and proteinuria.
AB  - BACKGROUND: The study was conducted in order to describe possible intraglomerular
      haemodynamic changes inducing proteinuria after 14 patients with chronic
      allograft dysfunction were converted from calcineurin inhibitors (CIs) to
      sirolimus without changing concomitant immunosuppression or antihypertensive
      treatment. METHODS: Creatinine, glomerular filtration rate (GFR), proteinuria,
      renal functional reserve (RFR) and effective renal plasma flow (ERPF) were
      determined before and 8 months after conversion. Intraglomerular pressure (P(G)),
      afferent arteriolar resistance (AAR) and efferent arteriolar resistance (EAR)
      were calculated using Gomez's formula. RESULTS: Creatinine (1.97 vs 2.075 mg/dl;
      P = 0.270) and GFR (40 vs 43 ml/min; P = 0.505) remained unchanged, proteinuria
      increased (338 vs 1146 mg/24 h; P = 0.006), RFR decreased (34.84 vs 13.47%; P =
      0.019), ERPF (248 vs 310.6 ml/min; P = 0.0625) and P(G) (42.72 vs 46.17 mmHg; P =
      0.0625) tendentially increased and AAR tendentially decreased (14.12 vs 10.28
      dyne/s/cm(5); P = 0.0625). CONCLUSION: After conversion, P(G) shows a tendency to
      increase and RFR decreases significantly-characteristics of hyperfiltration,
      which could possibly partially explain the increase of proteinuria. Therefore,
      the application of angiotensin-converting enzyme inhibitors or angiotensin II
      receptor blockers seems promising. To avoid hyperfiltration, conversion should be
      performed early when renal insufficiency is still moderate.

PMID- 16280370
TI  - Angiotensin II: a key factor in the inflammatory and fibrotic response in kidney
      diseases.
AB  - Angiotensin II (AngII) participates in the pathogenesis of renal diseases,
      through the regulation of two key processes inflammation and fibrosis. AT1 and
      AT2 are the main receptors of AngII. AT1 mediates most of the actions of AngII.
      This receptor regulates the expression of profibrotic factors, such as connective
      tissue growth factor (CTGF). The Smad signalling pathway and the Rho/Rho kinase
      system are two novel mechanisms involved in AngII-induced matrix regulation
      recently described. The role of AT2 receptors in renal pathophysiological
      processes is not fully elucidated. Experimental data suggest that AT2 receptors
      through activation of nuclear factor-kappaB participate in renal inflammatory
      cell recruitment. Studies in animal models of kidney injury have shown that the
      combined blockade of both AT1 and AT2 receptors, as well as the inhibition of the
      NF-kappaB pathway are necessary to stop the inflammatory process fully. On the
      whole, these data highlight the complex signalling systems activated by AngII and
      suggest novel potential targets to block fibrosis and inflammation in renal
      diseases.

PMID- 16280371
TI  - Indexing glomerular filtration rate for body surface area is useful in obese
      subjects.

PMID- 16280372
TI  - Lack of a centre effect in UK renal units: application of an artificial neural
      network model.
AB  - BACKGROUND: Dialysis centre effect has been suggested to influence survival in
      end-stage renal disease (ESRD) patients. Few studies over the past decade have
      commented on the existence of the centre effect using logistic regression models.
      METHODS: We used high quality prospectively collected data from the UK Renal
      Registry (UKRR) and created an artificial neural network model to predict
      mortality within 1 year in this cohort. We used a multitude of demographic
      variables including co-morbodities as well as relevant laboratory data to create
      a prognostic model. RESULTS: A highly efficient model for predicting 1 year
      mortality was created after restricting the model to use demographic and case
      enriched data [area under the receiver operating characteristic curve (AUROC) =
      0.974]. The addition of the dialysis centre code and centre size as input
      variables did not add to the efficiency of the model (AUROC = 0.962). Moreover,
      dialysis centre code or size alone was not predictive of mortality when applied
      to an artificial neuronal network architecture (AUROC = 0.649 and 0.628).
      CONCLUSION: Residual effects in previous studies may have been due to the non
      linear nature of the data and complex intervariable relationships. Centre size
      and other centre-related factors have no impact on survival on ESRD.

PMID- 16280373
TI  - Highlights of the epidemiology of renal replacement therapy in Central and
      Eastern Europe.
AB  - BACKGROUND: In the past 15 years, dramatic political and economic changes have
      occurred in Central and Eastern Europe (CEE) which also had a positive impact on
      the availability of renal replacement therapy. The aim of the present study was
      to analyse the progress achieved in the new millennium. METHODS: Data from 18 CEE
      countries collected during two independent surveys (1999 and 2002) were validated
      using information from national and ERA-EDTA registries, and analysed. RESULTS:
      The data collected from 18 CEE countries clearly document further development and
      improvement of renal replacement therapy in this region of Europe. In 63% of
      countries, the incidence rate had become comparable with that observed in more
      developed European countries. The two main modalities of dialysis, i.e.
      haemodialysis and peritoneal dialysis, are used. The frequency of the use of PD
      varies between 0.5% and nearly 37%. Privatization of dialysis units has started
      in 18 CEE countries. Currently between 2.5% (Russia) and 90% (Hungary) of
      patients are treated in non-public centres. Renal transplantation is quite well
      developed in half of the CEE states. In the states on the territory of the former
      Soviet Union, substantial progress in renal replacement therapy was achieved in
      the Baltic states, but the development in Byelorussia and Russia is still
      unsatisfactory. CONCLUSION: The availability and outcome of renal replacement
      therapy in the majority of states in CEE have become comparable with what is seen
      in more developed Western Europe. Nevertheless, large differences exist between
      individual countries. In particular, definite improvement is urgent in
      Byelorussia and Russia.

PMID- 16280374
TI  - Effect of previously failed kidney transplantation on peritoneal dialysis
      outcomes in the Australian and New Zealand patient populations.
AB  - BACKGROUND: There is limited information about the outcomes of patients
      commencing peritoneal dialysis (PD) after failed kidney transplantation. The aim
      of the present study was to compare patient survival, death-censored technique
      survival and peritonitis-free survival between patients initiating PD after
      failed renal allografts and those after failed native kidneys. METHODS: The study
      included all patients from the ANZDATA Registry who started PD between April 1,
      1991 and March 31, 2004. Times to death, death-censored technique failure and
      first peritonitis episode were examined by multivariate Cox proportional hazards
      models. For all outcomes, conditional risk set models were utilized for the
      multiple failure data, and analyses were stratified by failure order. Standard
      errors were calculated by using robust variance estimation for the cluster
      correlated data. RESULTS: In total, 13,947 episodes of PD were recorded in 23,579
      person-years. Of these, 309 PD episodes were started after allograft failure.
      Compared with PD patients who had never undergone kidney transplantation, those
      with failed renal allografts were more likely to be younger, Caucasian, New
      Zealand residents and life-long non-smokers with lower body mass index (BMI),
      poorer initial renal function and a longer period from commencement of the first
      renal replacement therapy to PD. On multivariate analysis, PD patients with
      failed kidney transplants had comparable patient mortality [weighted hazards
      ratio (HR) 1.09, 95% confidence interval (CI) 0.81-1.45, P = 0.582], death
      censored technique failure (adjusted HR 0.91, 95% CI 0.75-1.10, P = 0.315) and
      peritonitis-free survival (adjusted HR 0.92, 95% CI 0.72-1.16, P = 0.444) with
      those PD patients who had failed native kidneys. Similar findings were observed
      in a subset of patients (n = 5496) for whom peritoneal transport status was known
      and included in the models as a covariate. CONCLUSION: Patients commencing PD
      after renal allograft failure experienced outcomes comparable with those with
      failed native kidneys. PD appears to be a viable option for patients with failed
      kidney allografts.

PMID- 16280375
TI  - Efficacy of an educational programme for secondary school students on opinions on
      renal transplantation and organ donation: a randomized controlled trial.
AB  - CONTEXT: Organ shortage for transplantation is a crucial problem; educational
      interventions may increase donations and decrease opposition. OBJECTIVE: To test
      the efficacy of an educational programme on opinions on organ transplantation and
      kidney donation. DESIGN AND PARTICIPANTS: Cluster Randomized Controlled Trial:
      eight intervention and eight control schools were randomly selected from the 33
      public schools that agreed to participate. Targets: students in the last 2 years
      of secondary school (17-18 years); seven schools per group completed the study.
      EDUCATIONAL PROGRAMME: INTERVENTION: first questionnaire (anonymous); 2 h lesson
      in each class; 2 h general session with patients and experts; second
      questionnaire. CONTROL: questionnaires. MAIN OUTCOME MEASURES: Differences
      between questionnaires (comparative analysis); interest; satisfaction with the
      programme; (cross-sectional analysis). RESULTS: 1776 first, 1467 second
      questionnaires were retrieved. Living kidney donation: at baseline 78.8% of
      students would donate a kidney to a relative/friend in need. The answers were
      unaffected by type of school but depended on sex (females more prone to donate,
      P<0.001); the answers did not change after the lessons. Cadaveric kidney
      donation: baseline opinions were mixed (intervention schools: 31.5% yes, 33.7%
      no, 34.8% uncertain), depending on type of school (classical-scientific high
      schools more positive than technical institutes, P<0.001), sex (males more prone
      to donate, P<0.001). Answers on living and cadaveric donation were correlated
      (P<0.001). The educational intervention increased favourable (31.5 to 42.9%) and
      uncertain (34.8 to 41.1%) opinions and decreased negative ones (33.7 to 16%)
      (P<0.001). CONCLUSIONS: Educational interventions are effective in increasing
      interest and improving opinions about cadaveric organ donation.

PMID- 16280376
TI  - The suddenly speechless florist on chronic dialysis: the unexpected threats of a
      flower shop? Diagnosis: dialysis related Wernicke encephalopathy.

PMID- 16280377
TI  - Grafted kidney, native kidney and proteinuria after pre-emptive pancreas-kidney
      transplantation: questions and answers.

PMID- 16280378
TI  - The effects of methotrexate on Drosophila development, female fecundity, and gene
      expression.
AB  - Methotrexate (MTX), a synthetic folate analog, is a tight-binding inhibitor of
      dihydrofolate reductase (DHFR), a key enzyme for the biosynthesis of purines,
      thymidylate, and several amino acids. As a consequence, MTX decreases titres of
      reduced folates, interferes with DNA synthesis, and results in the arrest of
      rapidly proliferating cells, making it a drug of choice for the treatment of a
      variety of cancers and auto-immune disorders. MTX is also a known teratogen in
      all higher animals tested, but there is little information about the effects of
      this drug on invertebrates. Here we show that MTX has little effect on the
      survival of Drosophila melanogaster adult flies, but severely diminishes female
      fecundity. Reduced oviposition, coupled with aberrant egg morphologies, resulted
      in near sterility of MTX-treated females. Rare surviving progeny showed
      developmental abnormalities including larval tumors, and bristle, wing, eye, and
      leg defects. To determine if these phenotypes could be attributed solely to DHFR
      inhibition, microarray analysis was undertaken and included MTX-treated females,
      ovaries, and cell line samples. Genes encoding transcripts that were perturbed by
      the drug were verified using quantitative real-time RT-PCR. Many of these genes
      were involved in cell cycle regulation, signal transduction, transport, defense
      response, transcription, or various aspects of metabolism. These studies show
      that MTX treatment has multiple targets and, in addition, provides a new
      invertebrate model for the study of teratogenesis.

PMID- 16280379
TI  - Involvement of gelsolin in cadmium-induced disruption of the mesangial cell
      cytoskeleton.
AB  - Cadmium (Cd2+) is known to cause a selective disruption of the filamentous actin
      cytoskeleton in the smooth muscle-like renal mesangial cell. We examined the
      effect of Cd2+ on the distribution of the actin-severing protein, gelsolin. Over
      8 h, CdCl2 (10 microM) caused a progressive shift of gelsolin from a diffuse
      perinuclear and cytoplasmic distribution to a pattern decorating F-actin
      filaments. Over this time filaments were decreased in number in many cells, and
      membrane ruffling was initiated. Western blotting and 125I-F-actin gel overlays
      demonstrated an increase in actin-binding gelsolin activity in the cytoskeletal
      fraction of cell extracts following Cd2+ treatment. In in vitro polymerization
      assays, gelsolin acted as a nucleating factor and increased the rate of
      polymerization. Cytosolic extracts also increased the polymerization rate.
      Addition of Cd2+ together with gelsolin further increased the rate of
      polymerization. Gelsolin enhanced depolymerization of purified actin, and Cd2+
      partially suppressed this effect. However, cytoskeletal extracts from Cd2+
      treated cells also markedly increased depolymerization, suggesting further that
      Cd2+ may activate cellular component(s) such as gelsolin for actin binding. We
      conclude that a major effect of Cd2+ on the mesangial cell cytoskeleton is
      manifest through activating the association of gelsolin with actin, with
      gelsolin's severing properties predominating under conditions found in Cd2+
      treated cells.

PMID- 16280380
TI  - Effect of methoxychlor and estradiol on cytochrome p450 enzymes in the mouse
      ovarian surface epithelium.
AB  - Although the ovarian surface epithelium (OSE) is responsive to hormones and
      endocrine-disrupting chemicals, little information is available on the
      metabolizing capabilities of the OSE. Thus, we tested the hypothesis that the OSE
      is capable of expressing genes regulating phase I metabolism of estrogen and the
      estrogenic endocrine disruptor methoxychlor (MXC). To test this hypothesis, we
      isolated mouse OSE cells and cultured them with vehicle (dimethylsulfoxide;
      DMSO), 3 microM MXC, or 0.1 microM 17beta-estradiol (E2) +/- the anti-estrogen
      ICI 182,780 (1 microM) for 14 days. After culture, the cells were subjected to
      quantitative real-time polymerase chain reaction for cytochrome P450s (CYPs) 1A1,
      1B1, 2C29, and 1A2, and estrogen receptor alpha (ERalpha). Our results indicate
      that E2 and MXC did not alter the expression of CYP1A1 or CYP1A2. In contrast, E2
      significantly increased expression of CYP1B1 compared to controls (DMSO = 0.93 +/
      0.1, E2 = 3.12 +/- 0.64 genomic equivalents (GE), n = 4, p < or = 0.01). The E2
      induced increase in CYP1B1 was abolished by co-treatment with ICI 182,780 (0.41
      +/- 0.17 GE). MXC treatment did not affect CYP1B1 expression. Both MXC and E2
      increased expression of CYP2C29 (DMSO = 0.02 +/- 0.003; MXC = 0.04 +/- 0.008; E2
      = 0.46 +/- 0.03 GE, n = 4, p < or = 0.05). MXC- and E2-induced elevations in
      CYP2C29 were abolished by co-treatment with ICI 182,780 (0.02 +/- 0.005; 0.02 +/-
      0.07 GE). In addition, E2 increased ERalpha expression 15-fold compared to
      controls (DMSO = 1.10 +/- 0.09, E2 = 15.0 +/- 3.60 GE, n = 3, p < or = 0.05), and
      ICI 182,780 abolished the E2-induced increase in ERalpha expression (1.85 +/-
      1.09 GE). MXC treatment did not affect ERalpha expression. These data indicate
      that the OSE expresses enzymes known to metabolize native and xenoestrogens and
      that MXC and E2 modulate expression of some of them through ER-linked mechanisms.

PMID- 16280381
TI  - The paradoxical effects of lead in interferon-gamma knockout BALB/c mice.
AB  - It has been reported that lead (Pb) exposure enhances interleukin (IL)-4 and
      inhibits interferon-gamma (IFNgamma) production in wild-type (WT) BALB/c mice.
      Here, we examined Pb effects on immunity in IFNgamma knockout (KO) mice. Lead
      significantly enhanced serum IgG1 anti-keyhole limpet hemocyanin (KLH) levels in
      WT mice compared to the controls; Pb also increased serum IgG2a anti-KLH levels,
      but the IgG1:IgG2a ratio was greater with Pb. In addition, total serum IgE
      levels, but not IgE anti-KLH levels, were increased. In the KO mice, the serum
      IgG1, IgG2a, IgE anti-KLH, and total IgE levels were significantly lower than
      those of WT mice. Surprisingly, Pb significantly enhanced IgG1 and IgG2a anti-KLH
      levels in the KO mice. However, for these mice, unlike the WT mice, Pb caused a
      greater percentage change in IgG2a than in IgG1 anti-KLH, indicating less skewing
      toward type-2 immunoglobulins. Lead also enhanced the delayed-type
      hypersensitivity (DTH) response in WT mice. Not surprisingly, very low DTH
      occurred in the KO mice; however, Pb induced a strong KLH-specific DTH response.
      The in vivo Pb exposure significantly increased in vitro production of IL-4, IL
      5, and IL-10, but not IFNgamma, IL-2 and IL-12, by KLH-induced WT and KO spleen
      cells. In contrast to KLH, dinitrofluorobenzene contact hypersensitivity (DNFB
      CHS) was detected in all groups, and Pb did not affect this response, which
      suggests that Pb has only a slight effect on CD8+ T cell-related responses. As
      previously reported, Pb enhances Th2 responses in WT mice; however, in the KO
      mice, Pb enhanced Th1-related anti-KLH production and a Th2-related DTH. The Pb
      enhancement of DTH in IFNgamma-deficient mice is likely due to promotion of type
      2 cytokines and enhancement of major histocompatibility complex (MHC) class II
      expression.

PMID- 16280382
TI  - Smokeless tobacco impairs the antioxidant defense in liver, lung, and kidney of
      rats.
AB  - The present study was designed to evaluate the effects of long-term use of
      aqueous extract of gutkha (a form of smokeless tobacco) on the antioxidant
      defense status and histopathological changes in liver, lung, and kidney of male
      Wistar rats. Animals were orally administered aqueous extract of smokeless
      tobacco (AEST) at a low dose (96 mg/kg body weight per day) for 2 and 32 weeks,
      and at a high dose (960 mg/kg body weight per day) for 2 weeks. High-dose AEST
      for 2 weeks decreased the hepatic glutathione (GSH) and glutathione peroxidase
      (GPx), and increased lipid peroxidation (Lpx) by 17%, 19%, and 20%, respectively.
      Low-dose AEST for 32 weeks significantly decreased (p < 0.05) the antioxidant
      status in these organs. In liver, AEST decreased GSH levels and the activities of
      superoxide dismutase (SOD), catalase (CAT), and GPx by 34.6%, 29%, 17.1%, and
      17.4%, respectively, but it increased Lpx by 64%. In kidney, GSH, SOD, CAT, and
      GPx were decreased by 26.6%, 23%, 33%, and 18%, respectively, with an increase of
      Lpx by 65%. AEST decreased the lung GSH, SOD, CAT, and GPx, and increased lung
      Lpx by 43%, 28.5%, 37%, 40%, and 24%, respectively. However, no change in the
      plasma levels of vitamins A, C, and E were observed with AEST treatment.
      Histopathological findings suggest that administration of AEST at the high dose
      for 2 weeks or at the low dose for 32 weeks could cause mild to moderate
      inflammation in liver and lungs. In conclusion, a decrease in the antioxidant
      defense system and long-term inflammation caused by smokeless tobacco may be risk
      factors for gutkha-induced pathogenesis.

PMID- 16280383
TI  - The ribosomal protein rpL11 associates with and inhibits the transcriptional
      activity of peroxisome proliferator-activated receptor-alpha.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the
      nuclear receptor superfamily whose ligands, the peroxisome proliferators (PPs),
      are liver tumor promoters in rodents. Interaction cloning was performed using
      bacterially expressed PPARalpha to identify proteins involved in PP signaling.
      The ribosomal protein L11 (rpL11), a component of the large 60S subunit, was
      identified as a PPARalpha-associated protein. Since rpL11 is a regulator of p53
      and the cell cycle, the association between this protein and PPARalpha was
      examined in detail. PPARalpha-rpL11 interaction was confirmed using yeast and
      mammalian two-hybrid systems as well as in vitro pull-down assays. The
      association with rpL11 occurs within the D-domain (hinge-region) of PPARalpha.
      Unlike PPARalpha, the two closely related isoforms PPARbeta and gamma do not
      interact with rpL11. Cotransfection of mammalian cells with rpL11 resulted in
      ligand-dependent inhibition of transcriptional activity of PPARalpha. Ribosomal
      protein L11-mediated inhibition of gene expression is associated with decreased
      binding to the PPAR-response element (PPRE) DNA sequence. Release of rpL11 from
      the ribosome by serum deprivation or low-dose actinomycin D did not dramatically
      affect PPRE-driven luciferase activity when PPARalpha was overexpressed by
      cotransfection. However, when endogenous levels of PPARalpha are examined and
      rpL11 concentration is manipulated by expression by small interference RNA, the
      ability of peroxisome proliferator to induce PPRE-driven reporter activity and
      target gene mRNA is affected. These studies show that rpL11 inhibits PPARalpha
      activity and adds further evidence that ribosomal proteins play roles in the
      control of transcriptional regulation.

PMID- 16280384
TI  - Aflatoxin B1 alters the expression of p53 in cytochrome P450-expressing human
      lung cells.
AB  - Aflatoxin B1 (AFB1) is a potent dietary hepatocarcinogen in animals and probably
      in humans. Mutations (and altered expression) of the tumor suppresser gene p53
      have been observed in liver tumors from patients exposed to high dietary AFB1.
      Inhalation of AFB1-laden grain dusts has been associated with an increased
      incidence of lung cancer in humans as well. We examined the effects of low
      concentrations of AFB1 on the expression of p53 and MDM2 in human bronchial
      epithelial cells (BEAS-2B) transfected with cDNA for either cytochrome P450 (CYP)
      1A2 (B-CMV1A2) or CYP 3A4 (B3A4), two isozymes that are responsible for AFB1
      activation in human liver and possibly the lung. Untreated B-CMV1A2 and B3A4
      cells constitutively expressed p53. Exposure to a range (0.015-15 microM for 30
      min) of AFB1 concentrations caused a concentration-dependent decline in p53
      expression in B-CMV1A2 cells, and to a lesser extent, in B3A4 cells. The AFB1
      mediated decrease in p53 continued for at least 12 h after 30-min exposures to
      1.5 muM AFB(1). Mirroring the decrease in p53 expression was a concentration
      dependent increase in the expression of the 76-kDa MDM2 isoform in B-CMV1A2 and B
      3A4 cells. Interestingly, AFB1 did not induce DNA laddering, an indicator of
      apoptotic cell death, but proteolytic activation of caspase-3 was detected in
      AFB1-treated B-CVM1A2 cells. In total, these data show that low, environmentally
      relevant concentrations of AFB1 alter the expression of p53 and MDM2 in these
      human lung cells, and that cells that stably express CYP 1A2 were more
      susceptible to this effect than nontransfected, or 3A4-expressing cells.

PMID- 16280385
TI  - Impact of repeated exposure on the toxicokinetics of BDE 47 in mice.
AB  - 2,2',4,4'-Tetrabromodiphenyl ether (BDE 47) is the major polybrominated diphenyl
      ether (PBDE) found in environmental samples and human tissue despite its small
      contribution to global production and usage. Currently, three toxicokinetic
      studies are available investigating single-dose exposures; this is the first
      study to investigate toxicokinetic parameters following repeated exposure to BDE
      47. The disposition and excretion of BDE 47 was monitored in adult female C57BL/6
      mice for 5 days following ten consecutive 1.0-mg/kg oral doses and compared with
      results from our previous study. Results of the present study suggest greater
      retention of BDE 47 and nonlinear disposition patterns following repeated
      exposure to this dose in mice. No target tissues of sequestration or potential
      toxicity were determined; however, some tissues, such as the liver, demonstrated
      patterns of interest following repeated exposure that were not previously
      observed in acute toxicokinetic studies. Repeated exposure to BDE 47 results in
      higher concentrations remaining in adipose tissue, which demonstrates its
      potential for bioaccumulation. The data also suggest that excretion of BDE 47 may
      be decreased following repeated exposure. These results, in combination with
      evidence of its persistence and toxicity, underlie the need to further understand
      BDE 47 toxicokinetics across species at steady-state conditions.

PMID- 16280386
TI  - Genetic analysis of glutathione S-transferase A1 polymorphism in the Chinese
      population and the influence of genotype on enzymatic properties.
AB  - Genetic polymorphisms of human glutathione S-transferases (hGSTs) have important
      implications for drug efficacy and cancer susceptibility. hGSTA1 is the most
      abundant subfamily of hGSTs. The aim of this study was to investigate the
      distribution of hGSTA1 genetic polymorphism in the Chinese population and whether
      there exists the potential activity alterations caused by this polymorphism.
      Therefore, genomic DNA was extracted from peripheral blood of 140 healthy Chinese
      people and 11 normal liver tissues obtained from patients who had undergone liver
      surgery. Two variants in the promoter region of the hGSTA1 gene were identified
      by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP).
      Activities toward selected substrates of the wild type (hGSTA1*A) and variant
      (hGSTA1*B) were measured spectrometrically using S-9 fractions from liver
      samples. Delta5-androstene-3,17-dione (AD), cumene hydroperoxide (CuOOH), and 1
      chloro-2,4-dinitrobenzene (CDNB) were used as marker substrates toward hGSTA1,
      hGSTA, and hGST, respectively. The kinetic parameters (Km, Vmax, and Vmax/Km) of
      hGSTA1 were determined with different concentrations of AD. The results showed
      that, in the study population, the proportions of hGSTA1*A/*A, hGSTA1*A/*B, and
      hGSTA1*B/*B genotypes were 75.0, 24.3, and 0.7%, respectively, and the allele
      frequencies of hGSTA1*A and hGSTA1*B were detected to be 87.1 and 12.9%,
      respectively. The variant hGSTA1 showed a significantly decreased activity for AD
      isomerization as compared to the wild type. Kinetic analyses revealed that the
      V(max) value of the variant hGSTA1 was 48% of that of the wild type despite a Km
      value of 62% (p < 0.01). This means that the Vma)/Km) in the variant hGSTA1 was
      76%. These data indicate that the distribution of hGSTA1 gene is polymorphic in
      Chinese and is different from those in other racial populations. The promoter
      sequence polymorphism of the hGSTA1 gene is associated with decreased Km and Vmax
      values of the enzyme in individuals with the variant allele. This variant is also
      associated with a decrease in hGSTA1 activity toward preferred substrates. This
      altered activity, however, is accompanied by significant individual variation in
      the variant population.

PMID- 16280390
TI  - e-Health Initiative update: proceedings from the e-Health Technology Summit.

PMID- 16280388
TI  - Activation-induced deaminase cloning, localization, and protein extraction from
      young VH-mutant rabbit appendix.
AB  - Studies in mouse, human, and chicken suggest that activation-induced deaminase
      (AID) is involved in three known processes leading to antibody diversification:
      somatic hypermutation, gene conversion, and class-switch recombination.
      Developing rabbit appendix provides a particularly good site for studying all
      three of these B cell maturation events. We report here successful cloning of
      rabbit AID and isolation of AID protein from rabbit appendix-cell nuclear and
      cytoplasmic extracts. We succeeded in identifying and locating AID protein in
      cells by immunohistochemical and immunofluorescent staining techniques and
      examined colocalization of AID and other molecules important for Ab
      diversification. This report extends our knowledge about AID to a mammalian
      species that uses gene conversion to diversify rearranged Ig genes. Although much
      work remains to understand fully the mechanism of action of AID and its
      association with other cellular components, the rabbit system now offers a
      particularly useful model for future studies of these dynamics.

PMID- 16280391
TI  - Error reporting: patient safety's weakest link.

PMID- 16280392
TI  - Mandatory state-based error-reporting systems: current and future prospects.
AB  - The magnitude of medical errors documented in the 1999 Institute of Medicine
      report "To Err Is Human" encouraged health care leaders across the country to
      evaluate and improve current systems of care. To aid in this effort, the authors
      recommended and provided guidelines for establishing state-based mandatory error
      reporting systems. This repository for medical errors would allow experts to
      categorize, trend, and analyze data, generating institutional responsibility and
      increasing knowledge about medical mistakes. To be effective, these systems must
      employ efficient data collection methods, techniques for analysis, and feedback
      mechanisms. They must also engage institutional leaders in fostering a culture of
      safety and encourage multidisciplinary collaboration to learn from mistakes and
      improve microsystem-level processes. A review of current systems reveals extreme
      variation across states in each of these areas. However, initial successes do
      exist, suggesting the true potential of these systems and the need for continued
      evaluation as systems progress in future efforts.

PMID- 16280393
TI  - Health care provider use of private sector internal error-reporting systems.
AB  - The purpose of this study was to review the state of the art of private sector
      internal error-reporting systems and to begin to develop a classification system
      for comparing systems. Interviews were conducted to research and examine 9
      systems currently on the market. Analysis resulted in the following observations:
      (1) 7 of the systems are stand-alone, while 2 are part of larger hospital
      information systems; (2) most of the systems have been in existence for less than
      5 years; (3) acute care hospitals are the primary clients; (4) systems are
      capable of interfacing with other information systems and root-cause analysis
      programs; and (5) systems are browser based and accessible via the Internet
      and/or the provider's intranet. Additional studies are needed to determine the
      impact of these systems on health outcomes. However, one fact is clear: tracking
      incidents will not improve patient safety unless administrators close the
      feedback loop on quality.

PMID- 16280394
TI  - Understanding keys to successful implementation of electronic decision support in
      rural hospitals: analysis of a pilot study for antimicrobial prescribing.
AB  - Electronic clinical decision support systems (CDSS) have been hailed for their
      potential to improve clinical outcomes. Using a pretest/posttest design, an
      Internet-based CDSS designed to optimize antimicrobial prescribing was pilot
      tested for community-acquired pneumonia in 5 rural hospitals in southwestern
      Idaho. An antimicrobial management team was created in each hospital to address
      clinicians' perception of excessive time required for direct use of the CDSS. In
      pooled hospital data, agreement with CDSS recommendations improved to a
      statistically significant level. However, inspection of data at the individual
      hospital level demonstrated that almost all improvement occurred in a single
      hospital. Failure in the other hospitals appeared to be primarily a consequence
      of organizational and cultural barriers. These barriers are discussed to
      understand keys for successful future implementation of CDSS in rural hospitals,
      drawing on experience with cultural barriers from other industries, specifically
      aviation.

PMID- 16280395
TI  - Accuracy of administrative data for identifying patients with pneumonia.
AB  - The goal of this study was to determine the accuracy and the impact of 5
      different claims-based pneumonia definitions. Three International Classification
      of Diseases, Version 9, (ICD-9), and 2 diagnosis-related group (DRG)-based case
      identification algorithms were compared against an independent, clinical
      pneumonia reference standard. Among 10748 patients, 272 (2.5%) had pneumonia
      verified by the reference standard. The sensitivity of claims-based algorithms
      ranged from 47.8% to 66.2%. The positive predictive values ranged from 72.6% to
      80.8%. Patient-related variables were not significantly different from the
      reference standard among the 3 ICD-9-based algorithms. DRG-based algorithms had
      significantly lower hospital admission rates (57% and 65% vs 73.2%), lower 30-day
      mortality (5.0% and 5.8% vs 10.7%), shorter length of stay (3.9 and 4.1 days vs
      5.6 days), and lower costs (USD $4543 and USD $5159 vs USD $8585). Claims-based
      identification algorithms for defining pneumonia in administrative databases are
      imprecise. ICD-9-based algorithms did not influence patient variables in our
      population. Identifying pneumonia patients with DRG codes is significantly less
      precise.

PMID- 16280396
TI  - Interactive voice response reminder effects on preventive service utilization.
AB  - This study evaluated the effects of interactive voice response (IVR) system
      reminders to managed care organization (MCO) members to obtain mammograms,
      Papanicolaou (Pap) tests, and influenza immunizations. The MCO identified 3
      member cohorts and sent IVR reminders to get preventive services. Analyses
      employed claims data to examine relationships between IVR reminders and
      preventive service use 5 to 9 months post-intervention among members without
      prior utilization. Multivariate logistic regressions controlling for age, gender
      (for influenza immunizations), and risk stratum confirmed hypothesized
      relationships between intervention and preventive services: mammograms, odds
      ratio (OR) = 1.263 (95% confidence interval [CI] = 1.104, 1.444); Pap tests, OR =
      1.241 (1.107, 1.391); influenza immunizations, OR = 2.072 (1.665, 2.580). IVR
      reminders are associated with higher rates of mammograms, Pap tests, and
      influenza immunizations. Study limitations include unknown generalizability of
      results and possible self-selection. There is justification for more IVR
      interventions and research to enhance MCO members' preventive service
      utilization.

PMID- 16280397
TI  - Assessing quality and efficiency of discharge summaries.
AB  - Discharge summaries are intended to transfer important clinical information from
      inpatient to outpatient settings and between hospital admissions. The authors
      created a point scale that rated summaries in 4 key areas and applied the scale
      at a community teaching hospital over 3 years. Charts of 150 patients were
      selected equally from those discharged early and late in the academic year.
      Residents dictated all summaries after July 2003 using a prominently displayed
      template. Two residents and a senior physician assessed dictation quality.
      Considerable differences were found among raters, particularly in the evaluation
      of style. The average of the 3 raters' scores improved 21%, and dictation length
      decreased 67% after introduction of the template (P < .001). No relationship was
      found among service intensity (measured as chart weight), dictation length
      (measured in lines), and quality. Measured by a comprehensive rating scale, the
      quality of discharge summaries increased with use of a template while their
      length decreased.

PMID- 16280398
TI  - Quality of care of Medicare patients with diabetes in a metropolitan fee-for
      service primary care integrated delivery system.
AB  - Diabetes care in the United States is suboptimal. Although closed-panel health
      maintenance organizations (HMOs) and the Department of Veterans Affairs (VA)
      report performance superior to national norms, fee-for-service performance is
      uncertain. To address this issue, 3 outcome and 5 process indicators were
      measured for 2010 Medicare diabetes patients across 22 sites in a large, fee-for
      service primary care group practice. American Diabetes Association standards for
      glycemic control, low-density lipoprotein cholesterol, and blood pressure were
      met by 53%, 46%, and 19% of patients, respectively. Diabetes Quality Improvement
      Project/Alliance poor control markers for the same measures were exceeded by 9%,
      20%, and 54% of patients. Chart abstraction demonstrated annual eye examination,
      foot examination, and nephropathy screening rates of 16%, 49%, and 38%, while
      Medicare claims showed an annual eye examination rate of 63%. Observed processes
      and outcomes in this fee-for-service setting were superior to reported national
      performance and similar to the best performance in staff-model HMOs and the VA.

PMID- 16280400
TI  - The Agency for Healthcare Research and Quality's Effective Health Care Program:
      creating a dynamic system for discovering and reporting what works in health
      care.

PMID- 16280399
TI  - Case study: identifying potential problems at the human/technical interface in
      complex clinical systems.
AB  - Many who would like to improve patient safety in health care have advocated for
      the widespread adoption of computerized physician order entry and electronic
      medical records. However, unforeseen consequences of this new technology may put
      patients at greater risk of harm, not less. The authors present a clinical
      scenario that demonstrates system vulnerabilities in the interface between humans
      and such technology. Furthermore, the authors suggest that managers could
      anticipate these vulnerabilities by using techniques such as cause-and-effect
      analysis or failure mode and effect analysis, both before the installation of
      electronic medical records and as ongoing surveillance mechanisms. The case study
      demonstrates that adoption of technology is not a quick fix to the patient safety
      issue; proactive and ongoing efforts to address the human factors issues raised
      by the introduction of new technology will be required to prevent patient harm.

PMID- 16280404
TI  - Comparative quantitative acid-base analysis in coronary artery bypass, severe
      sepsis, and diabetic ketoacidosis.
AB  - The main objective of this study was to assess the relationship of standard base
      excess (SBE) to delta strong ion difference effective (DeltaSIDe) in critical
      illness. Critical illness is characterized by variable plasma nonvolatile weak
      acid components (DeltaA(-)), and SBE becomes discordant with DeltaSIDe. The
      author hypothesized that both acid-base models are equivalent when SBE and
      DeltaSIDe are corrected for DeltaA(-). A retrospective chart review was performed
      to assess this hypothesis by looking at changes in SBE, DeltaSIDe, and DeltaA(-)
      in 30 coronary artery bypass graft surgery patients, 30 severe sepsis patients,
      and 15 diabetic ketoacidosis patients. SBE equals the sum of the DeltaSIDe and
      DeltaA(-). The SBE quantifies the magnitude of the metabolic acid-base
      derangement, the DeltaSIDe quantifies the plasma strong cation/anion imbalance,
      and the DeltaA(-) quantifies the magnitude of the hypoalbuminemic alkalosis. The
      partitioning of SBE into physicochemical components can facilitate analyses of
      complex acid-base disorders in critical illness.

PMID- 16280405
TI  - Outcome of critically ill human immunodeficiency virus-infected patients in the
      era of highly active antiretroviral therapy.
AB  - The purpose of this study was to determine the effect of prior use of highly
      active antiretroviral therapy (HAART) on outcome of human immunodeficiency virus
      (HIV)- patients admitted to intensive care units (ICUs). This study was a
      retrospective chart review of 242 HIV-infected patients who required 259
      consecutive admissions to a university-affiliated hospital ICU during a 3-year
      period. Patient demographics, CD4 count, admission diagnosis, prior HAART,
      Pneumocystis jiroveci prophylaxis, length of stay, and ICU and hospital mortality
      were determined. Overall hospital mortality was 39%. Comparing patients who had
      received HAART before an ICU admission to those who had not, we found no
      difference between ICU or hospital mortality, need of mechanical ventilation, ICU
      and hospital length of stay, and incidence of P jiroveci. Pulmonary diagnosis was
      the most frequent ICU admission diagnosis (30%). Logistic regression analysis
      showed HIV-related illness and mechanical ventilation were significant
      independent predictors of increased hospital mortality.

PMID- 16280406
TI  - Use of admission troponin in critically ill medical patients.
AB  - Serum troponin I (TnI) is a sensitive marker of cardiac injury. A relation
      between elevated TnI and mortality has been suggested. In this retrospective
      chart review of 221 patients admitted to the medical intensive care unit (MICU)
      during a 6-month period, the authors studied the use of admission TnI levels in
      predicting mortality in MICU-admitted patients. Data retrieved included
      demographics, admission diagnosis, troponin, electrocardiogram, Acute Physiology
      and Chronic Health Evaluation (APACHE) II score, echocardiogram, requirements for
      mechanical ventilation and vasopressor support, development of multiorgan
      failure, mortality, and discharge disposition. There were 132 patients for whom
      TnI level was sent within 24 hours of admission; these patients comprised the
      study group. The median age was 70 years; 59% were female. The mean APACHE II
      score was 22. Troponin I was positive in 31% of patients (median level, 0.4 Ug/L;
      range 0-358 Ug/L). The hospital mortality was 39%. Positive TnI showed a weak
      association with intensive care unit (ICU) mortality (P = .049) but not with
      overall mortality. There was no significant correlation between admission TnI
      concentration and APACHE II score (P = .33), administration of vasopressor
      medications (P = .115), or development of multiorgan failure (P = .64). The
      authors concluded that there is no benefit in obtaining a routine admission
      troponin level in MICU patients when an acute coronary event is not suspected.

PMID- 16280408
TI  - In acute organophosphate poisoning, the efficacy of hemoperfusion on clinical
      status and mortality.
AB  - The aims of this study were to report experience in patients with organophosphate
      poisoning (OPP) and to discuss the potential role for hemoperfusion (HP) in the
      management of severe OPP. At the emergency service of a university hospital, 52
      patients with acute OPP were included in this retrospective study. The patients
      were divided into 2 groups (Group 1, severe poisoning, n = 25; and Group 2, mild
      poisoning, n = 27). All patients with mild OPP survived. Seven patients (28%) of
      the 25 with severe OPP died. This study supports previous data documenting that
      HP is unnecessary in the management of mild OPP. Although there was not a control
      group (severe poisoning without HP treatment) in this study, experience suggests
      that HP can be useful in severe cases. Reports from centers having experience
      with severe OPP can help clarify this controversial issue. Randomized controlled
      (prospective) studies investigating the possible beneficial effects of HP on
      patient survival in patients with severe OPP with control group are needed.

PMID- 16280407
TI  - Drotrecogin alfa (activated) in sepsis: initial experience with patient
      selection, cost, and clinical outcomes.
AB  - During a 1-year period, the authors examined clinical experience with drotrecogin
      alfa, activated for sepsis in a 24-bed medical-surgical intensive care unit.
      Drotrecogin alfa, activated was administered 46 times to 44 patients (3% of all
      intensive care unit admissions). Eighty-six percent of patients were on
      vasopressors; 95% were mechanically ventilated. Mean Acute Physiology and Chronic
      Health Evaluation II score was 22.0 at admission and 21.9 during the 24 hours
      before drug administration. The 28-day all-cause mortality was 36.4% and hospital
      mortality was 43.2%, trending higher (P = .10) than in the PROWESS study, which
      can be attributed to clinical use in patients who would not have met PROWESS
      study inclusion criteria. Failure to complete a 96-hour infusion of drotrecogin
      alfa, activated and transfer from another hospital or nursing home before
      treatment were associated with poor outcome. Total cost of hospital care,
      including mean drotrecogin alfa, activated drug cost of 7,312 US dollars,
      exceeded reimbursement by a mean of 18,227 US dollars.

PMID- 16280409
TI  - Linezolid-associated serotonin syndrome after concomitant treatment with
      citalopram and mirtazepine in a critically ill bone marrow transplant recipient.
AB  - Linezolid was initially discovered as an antidepressant because of its effect on
      blocking intracellular metabolism of serotonin, norepinephrine, and other
      biogenic amines. As time passed, it was realized that linezolid possessed
      antibacterial activity, and linezolid has been developed and marketed as such. In
      medicine we are quick to categorize drugs into specific classes as a mechanism to
      recall indication and use. By classifying linezolid as an antibacterial, it is
      common to forget about its antidepressant roots. A case report involving
      linezolid with citalopram and mirtazepine in the precipitation of serotonin
      syndrome in a critically ill bone marrow transplant patient is described in this
      article.

PMID- 16280410
TI  - Fulminant miliary tuberculosis with adult respiratory distress syndrome
      undiagnosed until autopsy: a report of 2 cases and review of the literature.
AB  - Despite an overall decline in the incidence of tuberculosis (TB), the percentage
      of cases representing miliary TB has remained stable. We report 2 cases of fatal
      miliary TB that remained unrecognized until autopsy, occurring within a 6-month
      period at 1 Detroit institution. These cases represent the wide range of
      presentation of miliary TB, from an acute fulminant course to a cryptic prolonged
      course with subtle clinical findings. Both cases shared a common end point with
      the development of adult respiratory distress syndrome.

PMID- 16280411
TI  - Intensive care of patients with human immunodeficiency virus infection: time to
      take another look.

PMID- 16280412
TI  - Linopirdine modulates calcium signaling and stimulus-secretion coupling in
      adrenal chromaffin cells by targeting M-type K+ channels and nicotinic
      acetylcholine receptors.
AB  - Adrenal chromaffin cells synthesize and release catecholamines and several other
      transmitters that play important physiological roles in the coordinated response
      to stress or danger. The main trigger for secretion is acetylcholine (ACh)
      released from splanchnic nerve terminals that activates nicotinic ACh receptors
      (nAChRs) on the chromaffin cells, causing membrane depolarization and Ca2+ entry
      primarily through voltage-gated Ca2+ channels (Ca-channels). G protein-coupled
      receptors (GPCRs) can also trigger secretion, and it has been suggested that
      closure of M-type K+ channels might contribute to this process. However, GPCRs
      have multiple effects on calcium signaling and secretion, including release of
      intracellular Ca2+ stores, activation of second messenger pathways and kinases,
      and Ca2+ entry through store/receptor-operated channels. Hence, the effects of M
      channel closure on [Ca2+]i signaling and transmitter release remain unclear. We
      have investigated the effects of linopirdine, a relatively selective blocker of M
      channels, on stimulus-secretion coupling in chromaffin cells. Linopirdine
      produced a small increase in [Ca2+]i in approximately 63% of cells because of
      influx through Ca-channels. However, this was not sufficient to promote
      catecholamine release. We also show that linopirdine reduced cholinergic
      stimulated increases in [Ca2+]i and secretion, primarily through potent block of
      nAChRs and a subtle effect on Ca2+ entry via Ca-channels. Hence, our data support
      the hypothesis that M-channels help control the excitability of chromaffin cells,
      but additional pathways need to be recruited by GPCRs to trigger catecholamine
      release. Furthermore, linopirdine potently targets nAChRs to modulate stimulus
      secretion coupling in adrenal chromaffin cells.

PMID- 16280413
TI  - A model of controlled acute hyperglycemia in rats: Effects of insulin and
      glucagon-like peptide-1 analog.
AB  - A rodent model of controlled acute hyperglycemia that is sensitive to glucose
      lowering agents insulin and glucagon-like peptide-1 (GLP-1) analog has been
      developed. The studies show that anesthesia could be induced in fasted rats with
      ketamine (100 mg/kg) plus a low dose of xylazine (5 mg/kg) without inducing the
      acute hyperglycemia typically associated with these agents. Under these
      conditions, continuous infusion of glucose (10 and 20%) via the jugular vein for
      30 to 150 min induced hyperglycemia in a time-dependent fashion. Administration
      of "loading" boluses of glucose (0.2-0.6 ml of a 20% solution) prior to
      continuous infusion of 10% glucose produced more immediate and sustained
      hyperglycemia. Plasma levels of a variety of glucoregulatory and stress hormones
      such as insulin, growth hormone, glucagon, and corticosterone were determined.
      Only glucagon levels changed significantly during induction and maintenance of
      hyperglycemia. The infusion of insulin (0.1 U/kg/h) or GLP-1 analog (10
      microg/kg/h) effectively lowered blood glucose from its elevated levels. Insulin
      produced a significant increase in glucagon levels, and GLP-1 analog produced a
      significant increase in insulin levels without any change in other
      glucoregulatory and stress hormone levels. In conclusion, the present studies
      identified a novel approach for the induction of anesthesia and surgical
      manipulations without inducing hyperglycemia and further defined an approach for
      producing acute hyperglycemia in a controlled fashion in rodents. This model will
      be beneficial to study the influence of hyperglycemia in acute models of critical
      illness where hyperglycemia develops following the precipitating event. This
      model was responsive to insulin and GLP-1 analog, both of which were effective in
      ameliorating hyperglycemia.

PMID- 16280414
TI  - Expression of a dominant negative FGF receptor in developing GNRH1 neurons
      disrupts axon outgrowth and targeting to the median eminence.
AB  - During development, neurons that synthesize and release gonadotropin-releasing
      hormone (GNRH1) extend their axons to the median eminence (ME) to establish
      neurosecretory contacts necessary for hormone secretion. Signals that coordinate
      this process are not known, but could involve the activation of fibroblast growth
      factor receptors (FGFRs) expressed on developing GNRH1 neurons. Using both whole
      animal and cell culture approaches, this study examines the direct role of FGFR
      signaling in the extension and guidance of GNRH1 axons to the ME. In vivo
      retrograde labeling with fluorogold (FG) first showed a significant reduction in
      the projections of GNRH1 axons to the circumventricular organs (including the ME)
      in transgenic mice expressing a dominant negative FGF receptor (dnFGFR) in GNRH1
      neurons. Using a primary GNRH1 neuronal culture system, we examined if
      compromised axon extension and directional growth led to the reduced axon
      targeting efficiency seen in vivo. Primary cultures of GNRH1 neurons were
      established from Embryonic Day 15.5 embryos, an age when GNRH1 neurons are
      actively targeting the ME. Cultured GNRH1 neurons expressing dnFGFR (dnFGFR
      neurons) exhibited attenuated activation of signaling pathways and reduced
      neurite outgrowth in response to FGF2. Further, dnFGFR neurons failed to
      preferentially target neurites toward cocultured ME explant and FGF2-coated
      beads, suggesting a defect in axon pathfinding. Together, these findings describe
      a direct role of FGFR signaling in the elongation and guidance of GNRH1 axons to
      the ME.

PMID- 16280415
TI  - Stress stimulates AMP-activated protein kinase and meiotic resumption in mouse
      oocytes.
AB  - This study examined the effects of three different cellular stresses on oocyte
      maturation in meiotically arrested mouse oocytes. Cumulus-cell enclosed oocytes
      (CEO) or denuded oocytes (DO) from immature, eCG-primed mice were cultured for 17
      18 h in dbcAMP-containing medium plus increasing concentrations of the metabolic
      poison, sodium arsenite, or the free radical-generating agent, menadione.
      Alternatively, oocytes were exposed to osmotic stress by pulsing with sorbitol
      and returned to control inhibitory conditions for the duration of culture.
      Arsenite and menadione each dose-dependently induced germinal vesicle breakdown
      (GVB) in both DO and CEO. DO, but not CEO, pulsed for 60 min with 500 mM sorbitol
      were stimulated to resume maturation. The lack of effect in CEO suggests that the
      cumulus cells may be playing a protective role in osmotic stress-induced GVB. The
      AMP-activated protein kinase (PRKA; formerly known as AMPK) inhibitors, compound
      C and araA, completely blocked the meiosis-stimulating effects of all the tested
      stresses. Western blots showed that acetyl-CoA carboxylase, an important
      substrate of PRKA, was phosphorylated before GVB, supporting a role for PRKA in
      stress-induced maturation. Together, these data show that a variety of stresses
      stimulate GVB in meiotically arrested mouse oocytes in vitro and suggest that
      this effect is mediated through activation of PRKA.

PMID- 16280416
TI  - Defective reproductive organ morphology and function in domestic rooster
      embryonically exposed to o,p'-DDT or ethynylestradiol.
AB  - Environmental pollutants with estrogenic activity have a potential to disrupt
      estrogen-dependent developmental processes. The objective of this study was to
      investigate if embryonic exposure to the environmental estrogens o,p'-DDT (1-(2
      chlorophenyl)-1-(4-chlorophenyl)-2,2,2-trichloroethane; 37, 75, 150 or 300
      microg/g egg) and EE2 (17alpha-ethynyl estradiol; 60 ng/g egg) affects the
      reproductive system in domestic roosters. Following egg injection on Embryonic
      Day 4, the newly hatched chicks were sexed by cloacal inspection. A skewed
      phenotypic sex ratio with overrepresentation of chicks deemed as females was
      observed in the groups exposed to the three highest doses of o,p'-DDT but not in
      the EE2-exposed group. Normal sex ratios were observed in all groups at
      adulthood. However, a cloacal deformation seemed to remain in the adult roosters,
      causing an abnormal semen flow upon semen collection. Semen yield was
      significantly reduced in both o,p'-DDT-exposed and EE2- exposed birds, whereas
      semen quality was unaffected. When killed, deformations of the left testis were
      found in all treatment groups. Image analysis revealed a reduced seminiferous
      tubular area in the roosters exposed to the two highest doses of o,p'-DDT.
      Embryonic exposure to o,p'-DDT caused decreased comb weight and right-spur
      diameter, while EE2 only affected right-spur diameter. In conclusion, this study
      shows that embryonic exposure to estrogenic compounds can induce permanent
      effects in male birds. The effects of the two studied compounds were partly
      similar but o,p'-DDT also induced alterations not seen in the EE2-treated birds.

PMID- 16280418
TI  - Changes in the odor quality of androstadienone during exposure-induced
      sensitization.
AB  - Androstadienone is a steroid found in human sweat and other secretions. It has
      been widely proposed as a candidate for a human pheromone. As an odorant it
      possesses some unique properties. Here we demonstrate that, firstly, there is a
      very wide range of thresholds in the human population, and they are not normally
      distributed. Secondly, repetitive exposure causes a decrease in detection
      threshold of more than four orders of magnitude, and thirdly, accompanying this
      sensitization process is a change in the perceived odor quality. Those with low
      to intermediate sensitivities ascribe to it a wide range of odor descriptors
      across the hedonic scale, but as these individuals become sensitized, their
      description changes to predominantly putrid. We propose that this change in odor
      quality reflects the presence of at least two receptor populations for
      androstadienone; a low-affinity receptor conveying pleasant odor qualities and a
      high-affinity receptor mediating unpleasant odor qualities. We further propose
      that repetitive exposure results in the increased expression of the high-affinity
      receptor thereby shifting the balance of perception to the negative end of the
      hedonic scale.

PMID- 16280417
TI  - Smooth muscle and purinergic contraction of the human, rabbit, rat, and mouse
      testicular capsule.
AB  - The smooth-muscle cells of the testicular capsule (tunica albuginea) of man, rat,
      and mouse were examined by electron microscopy. They were characteristically
      flattened, elongated, branching cells and diffusely incorporated into the
      collagenous matrix and did not form a compact muscle layer. Contractile and
      synthetic smooth-muscle cell phenotypes were identified. Nerve varicosities in
      close apposition to smooth muscle were seen in human tissue. Contractions induced
      by adenosine 5'-triphosphate (ATP), alpha, beta-methylene ATP, noradrenaline
      (NA), acetylcholine (ACh), and electrical field stimulation (EFS) of autonomic
      nerves were investigated. Nerve-mediated responses of the rabbit and human tunica
      albuginea were recorded. The EFS-induced human responses were completely
      abolished by prazosin. In the rabbit, EFS-induced contractile responses were
      reduced by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid by 36% and by
      prazosin by 77%. Both antagonists together almost completely abolished all EFS
      induced contractions. The human tunica albuginea was contracted by NA, ATP, and
      alpha, beta-methylene ATP, but not by ACh. The rabbit and rat tunica albuginea
      were contracted by NA, ATP, alpha, beta-methylene ATP, and ACh. The mouse tunica
      albuginea was contracted by ACh, ATP, and alpha, beta-methylene ATP, but relaxed
      to NA. Immunohistochemical studies showed that P2X1 (also known as P2RX1) and
      P2X2 (also known as P2RX2) receptors were expressed on the smooth muscle of the
      rodent testicular capsule, expression being less pronounced in man. The
      testicular capsule of the rat, mouse, rabbit, and man all contain contractile
      smooth muscle. ATP, released as a cotransmitter from sympathetic nerves, can
      stimulate the contraction of rabbit smooth muscle. Human, rat, and mouse
      testicular smooth muscle demonstrated purinergic responsiveness, probably
      mediated through the P2X1 and/or P2X2 receptors.

PMID- 16280419
TI  - Diet-heart hypothesis: will diversity bring reconciliation?

PMID- 16280420
TI  - Dietary protein content and the diet's net acid load: opposing effects on bone
      health.

PMID- 16280421
TI  - Obesity in older adults: technical review and position statement of the American
      Society for Nutrition and NAASO, The Obesity Society.
AB  - Obesity causes serious medical complications and impairs quality of life.
      Moreover, in older persons, obesity can exacerbate the age-related decline in
      physical function and lead to frailty. However, appropriate treatment for obesity
      in older persons is controversial because of the reduction in relative health
      risks associated with increasing body mass index and the concern that weight loss
      could have potential harmful effects in the older population. This joint position
      statement from the American Society for Nutrition and the NAASO, The Obesity
      Society reviews the clinical issues related to obesity in older persons and
      provides health professionals with appropriate weight-management guidelines for
      obese older patients. The current data show that weight-loss therapy improves
      physical function, quality of life, and the medical complications associated with
      obesity in older persons. Therefore, weight-loss therapy that minimizes muscle
      and bone losses is recommended for older persons who are obese and who have
      functional impairments or medical complications that can benefit from weight
      loss.

PMID- 16280422
TI  - Mediterranean diet in relation to body mass index and waist-to-hip ratio: the
      Greek European Prospective Investigation into Cancer and Nutrition Study.
AB  - BACKGROUND: Adherence to a Mediterranean diet has been reported to increase
      longevity, but concerns have been expressed that such a diet may promote
      overweight and obesity. OBJECTIVE: The objective was to investigate whether
      adherence to the traditional Mediterranean diet, as operationalized in a
      Mediterranean diet score, is associated with body mass index (BMI) and waist-to
      hip ratio (WHR). DESIGN: In a general population sample of 23,597 adult men and
      women participating in the Greek European Prospective Investigation into Cancer
      and Nutrition Study, a validated food-frequency questionnaire was interviewer
      administered, and anthropometric, sociodemographic, physical activity, and other
      lifestyle characteristics were recorded. BMI and WHR were regressed on a score
      that reflects adherence to the traditional Mediterranean diet and potentially
      confounding variables. RESULTS: In models in which total energy intake was
      included, adherence to the Mediterranean diet was unrelated to BMI in both sexes
      and was weakly related to WHR only in women. When energy intake was not
      controlled for, a 2-point increase in the score was found to correspond to
      increases of approximately 650 and 150 g in the weight of an average-height man
      and woman, respectively, whereas the WHR was found to increase by approximately
      0.001 units in men and 0.004 units in women. CONCLUSIONS: Adherence to a
      Mediterranean diet was essentially unrelated to BMI, with small differences
      depending on model choice and having no practical consequences. Overweight is a
      genuine problem in Greece and perhaps other Mediterranean countries, but it is
      likely to be related to limited physical activity in conjunction with excessive
      positive energy balance.

PMID- 16280423
TI  - Factors influencing variation in basal metabolic rate include fat-free mass, fat
      mass, age, and circulating thyroxine but not sex, circulating leptin, or
      triiodothyronine.
AB  - BACKGROUND: Basal metabolic rate (BMR) is the largest component of daily energy
      demand in Western societies. Previous studies indicated that BMR is highly
      variable, but the cause of this variation is disputed. All studies agree that
      variation in fat-free mass (FFM) plays a major role, but effects of fat mass
      (FM), age, sex, and the hormones leptin, triiodothyrionine (T3), and thyroxine
      (T4) remain uncertain. OBJECTIVE: We partitioned the variance in BMR into within-
      and between-subject effects and explored the roles of FFM, FM, bone mineral
      content, sex, age, and circulating concentrations of plasma leptin, T3, and T4.
      DESIGN: This was a cross-sectional study of 150 white adults from northeast
      Scotland, United Kingdom. RESULTS: Only 2% of the observed variability in BMR was
      attributable to within-subject effects, of which 0.5% was analytic error. Of the
      remaining variance, which reflected between-subject effects, 63% was explained by
      FFM, 6% by FM, and 2% by age. The effects of sex and bone mineral content were
      not significant (P > 0.05). Twenty-six percent of the variance remained
      unexplained. This variation was not associated with concentrations of circulating
      leptin or T3. T4 was not significant in women but explained 25% of the residual
      variance in men. CONCLUSIONS: Our data confirm that both FFM and FM are
      significant contributors to BMR. When the effect of FM on BMR is removed, any
      association with leptin concentrations disappears, which suggests that previous
      links between circulating leptin concentrations and BMR occurred only because of
      inadequate control for the effects of FM.

PMID- 16280424
TI  - Acute in vivo elevation of intravascular triacylglycerol lipolysis impairs
      peripheral T cell activation in humans.
AB  - BACKGROUND: Previous studies have shown suppressive effects of polyunsaturated
      fatty acids (PUFAs) on T cell proliferation, but the precise mechanism for this
      effect has not been fully investigated in vivo in humans. OBJECTIVE: The
      objective was to determine whether this effect is the result of altered T cell
      membrane properties and impaired CD3- and CD28-mediated signaling in vivo in
      humans. DESIGN: Peripheral T cells were isolated from healthy subjects before and
      2 h after an intravenous infusion of heparin plus a PUFA-rich lipid emulsion
      during a euglycemic hyperinsulinemic clamp to induce a 2.5-fold elevation in
      plasma linoleic acid concentration without significant change in plasma total
      free fatty acid concentrations. RESULTS: Intravenous infusion of heparin plus the
      lipid emulsion reduced peripheral T cell membrane fluidity and altered lipid raft
      organization, both of which were associated with reduced T cell proliferation
      after stimulation with CD3 plus CD28. Tyrosine phosphorylation of linker of
      activated T cells and activation of protein kinase B in T cells were also
      impaired without a reduction in T cell receptor expression. In addition, acute
      PUFA elevation was associated with a reduction in T cell membrane cholesterol
      exchange with the cellular milieu ex vivo. CONCLUSIONS: A selective increase in
      plasma linoleic acid concentration and in intravascular lipolysis has a
      suppressive effect on peripheral T cell CD28-dependent activation, and this
      effect is associated with changes in plasma membrane properties. Our results have
      important implications for nutritional therapy in patients at high risk of septic
      complications and may also be of relevance to postprandial lipid metabolism
      disorders such as insulin resistance and type 2 diabetes.

PMID- 16280425
TI  - Individual variability in cardiovascular disease risk factor responses to low-fat
      and low-saturated-fat diets in men: body mass index, adiposity, and insulin
      resistance predict changes in LDL cholesterol.
AB  - BACKGROUND: Although reductions in total and saturated fat consumption are
      recommended to reduce the risk of cardiovascular disease, individual variability
      in plasma lipid responses exists. OBJECTIVE: Our aim was to determine the effect
      of adiposity and insulin resistance on the lipoprotein response to diets lower in
      total and saturated fat than the average American diet (AAD). DESIGN: A
      randomized, double-blind, 3-period crossover controlled feeding design was used
      to examine the effects on plasma lipids of 3 diets that differed in total fat:
      the AAD [designed to contain 38% fat and 14% saturated fatty acids (SFAs)], the
      Step I diet (30% fat with 9% SFAs), and the Step II diet (25% fat with 6% SFAs).
      The diets were fed for 6 wk each to 86 free-living, healthy men aged 22-64 y at
      levels designed to maintain weight. RESULTS: Compared with the AAD, the Step I
      and Step II diets lowered LDL cholesterol by 6.8% and 11.7%, lowered HDL
      cholesterol by 7.5% and 11.2%, and raised triacylglycerols by 14.3% and 16.2%,
      respectively. The Step II diet response showed significant positive correlations
      between changes in both LDL cholesterol and the ratio of total to HDL cholesterol
      and baseline percentage body fat, body mass index, and insulin. These
      associations were largely due to smaller reductions in LDL cholesterol with
      increasing percentage body fat, body mass index, or insulin concentrations.
      Subdivision of the study population showed that the participants in the upper one
      half of fasting insulin concentrations averaged only 57% of the reduction in LDL
      cholesterol with the Step II diet of the participants in the lower half.
      CONCLUSION: Persons who are insulin resistant respond less favorably to Step II
      diets than do those who are insulin sensitive.

PMID- 16280426
TI  - The Medi-RIVAGE study: reduction of cardiovascular disease risk factors after a 3
      mo intervention with a Mediterranean-type diet or a low-fat diet.
AB  - BACKGROUND: Epidemiologic studies link Mediterranean-type diets to a low
      incidence of cardiovascular disease; however, few dietary intervention studies
      have been undertaken, especially in primary prevention. OBJECTIVES: In the
      Mediterranean Diet, Cardiovascular Risks and Gene Polymorphisms (Medi-RIVAGE)
      study, the effects of a Mediterranean-type diet (Med group) or a low-fat diet
      (low-fat group) on risk factors were evaluated in 212 volunteers (men and women)
      with moderate risk factors for cardiovascular disease. DESIGN: After the 3-mo
      dietary intervention, changes in many risk factors were evaluated. Dietary
      questionnaires and plasma nutritional markers were used to test compliance.
      RESULTS: Although the dietary goals were only partially reached, changes in
      dietary habits were observed in both groups (n = 169): protein, carbohydrate, and
      fiber intakes increased and fat quality (decreased saturated fat and increased
      monounsaturated or polyunsaturated fat) improved. BMI, total and triacylglycerol
      rich lipoprotein (TRL) cholesterol, triacylglycerols, TRL triacylglycerols,
      apolipoproteins A-I and B, insulinemia, glycemia, and the homeostasis model
      assessment score were significantly lower after 3 mo. The reductions in total
      cholesterol, triacylglycerols, and insulinemia remained significant after
      adjustment for BMI. There was a trend for a diet-by-time interaction for LDL
      cholesterol (P = 0.09). Our data predicted a 9% reduction in cardiovascular
      disease risk with the low-fat diet and a 15% reduction with this particular
      Mediterranean diet. CONCLUSION: After a 3-mo intervention, both diets
      significantly reduced cardiovascular disease risk factors to an overall
      comparable extent.

PMID- 16280427
TI  - Low-fat dairy consumption and reduced risk of hypertension: the Seguimiento
      Universidad de Navarra (SUN) cohort.
AB  - BACKGROUND: Some observational studies have shown a beneficial effect of dairy
      consumption on blood pressure, especially in overweight and relatively young (<40
      y) persons. However, no results from prospective studies conducted in a free
      living population exist that show this association in middle-aged adults.
      OBJECTIVE: The aim of the present study was to assess whether total, low-fat, and
      whole-fat dairy consumption was associated prospectively with the risk of
      hypertension. DESIGN: This was a prospective study conducted in 5880 university
      graduates in Spain, aged >20 y in 2000 (mean age: 37 y), free of hypertension and
      cardiovascular disease at baseline, and followed-up with mailed questionnaires
      for a median of 27 mo. Dairy consumption was assessed with a previously validated
      semiquantitative food-frequency questionnaire. RESULTS: One hundred eighty new
      cases of hypertension were identified. The hazard ratio of hypertension between
      extreme quintiles of low-fat dairy product consumption was 0.46 (95% CI: 0.26,
      0.84; P for trend = 0.02) after adjustment for the main known risk factors for
      hypertension and several dietary factors. No significant association between
      whole-fat dairy products or total calcium intake and incident hypertension was
      seen. CONCLUSION: In this Mediterranean cohort, low-fat dairy consumption, but
      not whole-fat dairy consumption, was associated with a lower risk of incident
      hypertension.

PMID- 16280428
TI  - Fetal programming of body composition: relation between birth weight and body
      composition measured with dual-energy X-ray absorptiometry and anthropometric
      methods in older Englishmen.
AB  - BACKGROUND: Reduced fetal growth is associated with differences in body
      composition in adult life that may predispose to cardiovascular disease and
      diabetes. Most published data are based on simple anthropometric measures, which
      incompletely describe body composition. OBJECTIVE: The objective was to assess
      body composition and fat distribution by using dual-energy X-ray absorptiometry
      (DXA). DESIGN: This was a case-control study of 64-72-y-old white men (n = 32)
      with a low (mean: 2.76 kg) or high (mean: 4.23 kg) birth weight. RESULTS:
      Compared with the high-birth-weight group, after adjustment for weight and
      height, the low-birth-weight group had a higher percentage body fat (29.31%
      compared with 25.33%; P = 0.029) and fat mass (P = 0.039) but a lower fat-free
      soft tissue (56.32 compared with 59.22 kg; P = 0.024), muscle mass (27.25
      compared with 29.22 kg; P = 0.022), and muscle-to-fat ratio. Low birth weight was
      also associated with a higher trunk-to-limb fat ratio after control for total fat
      mass (1.42 compared with 1.16; P = 0.005) or percentage body fat (P = 0.041). The
      same body mass index predicted a greater percentage body fat (P = 0.019) in the
      low- than in the high-birth-weight group, and the same ratio of trunk-to-limb
      skinfold thickness (or waist-to-hip ratio) predicted a higher trunk-to-limb fat
      ratio (P < 0.01). CONCLUSION: Lifelong differences in adult body composition and
      fat distribution between the low- and high-birth-weight groups are consistent
      with programming in early life. The use of BMI to predict percentage body fat and
      the use of the trunk-to-limb skinfold thickness ratio (and waist-to-hip ratio) to
      predict the trunk-to-limb fat ratio measured by DXA can be misleading when low-
      and high-birth-weight groups are compared.

PMID- 16280429
TI  - Estimation of total-body and limb muscle mass in hemodialysis patients by using
      multifrequency bioimpedance spectroscopy.
AB  - BACKGROUND: Skeletal muscle mass can be measured noninvasively with magnetic
      resonance imaging (MRI), but this is time-consuming and expensive. OBJECTIVE: We
      evaluated the use of multifrequency bioimpedance spectroscopy (BIS) measurements
      of intracellular volume (ICV) to model total-body skeletal muscle mass (TBMM) and
      limb skeletal muscle mass in hemodialysis patients. DESIGN: TBMM was measured by
      MRI in 20 male and 18 female hemodialysis patients with a median (range) age of
      54 y (33-73 y), weight of 78.9 kg (43.2-120 kg), and body mass index (BMI; in
      kg/m2) of 27.3 (19.4-46.6). We measured total body water (TBW) by using D2O
      dilution, extracellular volume (ECV) as bromide space, and ICV as TBW minus
      bromide space. Total body potassium (TBK) measured as 40K was used as an
      independent model of TBMM. BIS was used to measure whole-body TBW (ankle to
      wrist) and TBW in the arms and legs. BIS-estimated ICV was used to construct
      models to calculate limb muscle mass and TBMM. The latter was compared with
      models derived from isotopic methods. RESULTS: BIS yielded a model for TBMM [TBMM
      = 9.52 + 0.331 x ICV + 2.77 (male) + 0.180 x weight (kg) - 0.133 x age] (R2 =
      0.937, P < 0.0001) as precise as TBK-measured TBMM [TBMM = 1.29 + 0.00453 x TBK
      (mEq) + 1.46 (male) + 0.144 x weight (kg) - 0.0565 x age] (R2 = 0.930, P <
      0.0001) or isotopic methods. BIS models were also developed for measuring leg and
      arm muscle mass. CONCLUSION: BIS provides an estimate of TBMM that correlates
      well with isotopic methods in approximating values obtained by MRI and can be
      used to estimate limb muscle mass.

PMID- 16280430
TI  - Body fat distribution, body composition, and respiratory function in elderly men.
AB  - BACKGROUND: Most population studies have reported weak or nonsignificant
      associations between body mass index (BMI; in kg/m2) and lung function.
      OBJECTIVE: This study focused on the distinct effects of fat distribution and
      body composition on lung function and examined these relations in elderly men.
      DESIGN: The study was a cross-sectional evaluation of 2744 men aged 60-79 y who
      were free of cardiovascular disease and cancer and were drawn from general
      practices in 24 British towns. Anthropometric and body-composition [including fat
      mass (FM), fat-free mass (FFM), and percentage body fat (%BF) evaluated with
      bioelectric impedance] measurements were made, and lung function was examined by
      using spirometry. RESULTS: Height-standardized forced expiratory volume in 1 s
      (FEV1) was diminished only in lean (BMI < 22.5) and obese (BMI > or = 30) men,
      but forced vital capacity (FVC) tended to decrease with increasing BMI (P <
      0.01). All other measures of adiposity [ie, waist circumference (WC), waist-hip
      ratio (WHR), FM, and %BF] were significantly and inversely related to FEV1 and
      FVC after adjustment for confounders, including age and cigarette smoking (all: P
      < 0.05). This was seen both in nonobese (BMI < 30) and obese men. FFM was
      positively associated with FEV1 (P = 0.03) and to a lesser extent with FVC.
      Higher BMI and FFM were both associated with reduced odds of a low FEV1-FVC ratio
      (ie, <70%). CONCLUSION: Total body fat and central adiposity are inversely
      associated with lung function, but increased FFM reflecting increases in muscle
      mass is associated with increased lung function and lower odds of low FEV1:FVC in
      the elderly.

PMID- 16280432
TI  - Functional magnetic resonance imaging of human hypothalamic responses to sweet
      taste and calories.
AB  - BACKGROUND: Evidence exists that beverages do not trigger appropriate
      anticipatory physiologic responses, such as cephalic phase insulin release.
      Therefore, it is of interest to elucidate the food properties necessary for
      triggering adaptive responses. Previously, we found a prolonged dose-dependent
      decrease in the hypothalamic functional magnetic resonance imaging signal after
      ingestion of a glucose solution. OBJECTIVES: The aims of the present study were
      to measure the effects of sweet taste and energy content on the hypothalamic
      response to glucose ingestion and to measure the concomitant changes in blood
      glucose and insulin concentrations. DESIGN: Five healthy, normal-weight men
      participated in a randomized crossover design trial. The subjects were scanned 4
      times for 37 min on separate days with functional magnetic resonance imaging.
      After 7 min, they ingested 1 of the following 4 stimuli (300 mL of each): water
      (control), a glucose solution, an aspartame (sweet taste) solution, or a
      maltodextrin (nonsweet carbohydrate) solution. RESULTS: Glucose ingestion
      resulted in a prolonged and significant signal decrease in the upper hypothalamus
      (P < 0.05). Water, aspartame, and maltodextrin had no such effect. Glucose and
      maltodextrin ingestions resulted in similar increases in blood glucose and
      insulin concentrations. However, only glucose triggered an early rise in insulin
      concentrations. Aspartame did not trigger any insulin response. CONCLUSIONS: Our
      findings suggest that both sweet taste and energy content are required for a
      hypothalamic response. The combination of sweet taste and energy content could be
      crucial in triggering adaptive responses to sweetened beverages.

PMID- 16280431
TI  - The relation of sugar intake to beta cell function in overweight Latino children.
AB  - BACKGROUND: Few studies have investigated the association between sugar intake
      and insulin dynamics in children, and none have examined this association in
      overweight Latino youth. OBJECTIVE: We aimed to examine the relation between
      dietary components, especially sugar intake, and insulin dynamics in overweight
      Latino youth. DESIGN: We examined 63 overweight Latino children aged 9-13 y.
      Dietary intake was determined by 3-d records, and body composition was measured
      with dual-energy X-ray absorptiometry. Insulin sensitivity (S(I)), acute insulin
      response (AIR), and disposition index (an index of beta cell function) were
      measured by using a frequently sampled intravenous-glucose-tolerance test and
      minimal modeling. Hierarchical regression analysis ascertained the potential
      independent relation between insulin dynamics and dietary components. RESULTS:
      The relation between macronutrient intake and any variable related to insulin
      dynamics was not significant. However, higher total sugar intake, although not
      related to S(I), was significantly associated with lower AIR (beta = -0.296, P =
      0.045) and lower beta cell function (beta = -0.421, P = 0.043), independent of
      the covariates age, sex, body composition, Tanner stage, and energy intake. Sugar
      sweetened beverage intakes trended toward inverse association with lower AIR
      (beta = -0.219, P = 0.072) and beta cell function (beta = -0.298, P = 0.077).
      CONCLUSIONS: In overweight Latino children, higher intakes of sugar and sugar
      sweetened beverages were associated with lower AIR and disposition index, which
      suggested that these children already have early signs of poor beta cell
      function. These results emphasize the need for early nutritional interventions to
      reduce daily sugar intake in overweight Latino children and potentially reduce
      their risk for type 2 diabetes.

PMID- 16280433
TI  - Dysprosium as a nonabsorbable fecal marker in studies of zinc homeostasis.
AB  - BACKGROUND: Dysprosium is a nonabsorbable rare earth element that has had
      successful application as a marker for fecal excretion of unabsorbed zinc.
      OBJECTIVE: Our goals were 1) to evaluate the efficacy of administering dysprosium
      with all meals over several days as a method of determining the completeness of
      fecal collections, 2) to determine the similarity of gastrointestinal transit
      kinetics and excretion patterns of dysprosium and zinc tracer administered
      simultaneously over several days, and 3) to evaluate alternative methods of using
      the data for fecal excretion of orally administered zinc tracer and dysprosium to
      measure the fractional absorption of zinc. DESIGN: 70Zn and dysprosium were
      administered orally with all meals for 5 consecutive days to 7 healthy, free
      living adults consuming a constant diet based on habitual intake. Additional
      tracers, 67Zn and 68Zn, were administered intravenously. Urine and fecal samples
      were collected during tracer administration and for 8 d after the last dose.
      Isotope ratios were measured in urine and feces, and total zinc and dysprosium
      were measured in fecal samples. RESULTS: The mean recovery of dysprosium was
      101.3 +/- 2.4%. The zinc oral tracer and dysprosium had similar fecal excretory
      patterns; the correlation coefficient for 70Zn and dysprosium in fecal samples
      exceeded 0.99 (P < 0.0001) for each subject. Fractional zinc absorption
      measurements using various dysprosium methods correlated well (r > 0.95) with
      those from the fecal monitoring and dual-isotope-tracer ratio methods.
      CONCLUSION: Administration of dysprosium is a useful means of determining the
      completeness of fecal collections and of measuring zinc absorption.

PMID- 16280434
TI  - Iron supplement use and iron status among US adults: results from the third
      National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Patients with hemochromatosis are instructed to avoid taking
      supplemental iron. Whether supplemental iron intakes lead to higher iron status
      among healthy persons remains less clear. OBJECTIVE: The objective was to
      ascertain whether supplemental iron intakes are associated with increases in iron
      transport (transferrin saturation) and stores (serum ferritin) among US adults
      aged > or = 19 y. DESIGN: We analyzed data for 5948 adults from whom a fasting
      serum sample was collected during the third National Health and Nutrition
      Examination Survey. We used multivariable linear regression and analysis of
      variance to assess the association of supplemental iron intake with iron
      transport and stores among men (aged 19-30 y or > 30 y) and women (nonpregnant
      premenopausal or postmenopausal); multiple comparison tests were also performed.
      RESULTS: Healthy adults who took supplements containing average daily amounts of
      iron at < or = 3 times the recommended dietary allowance (RDA) did not have
      significantly higher iron transport or stores than did those who did not take
      supplements. In younger men, the intake of > 32 mg Fe/d (> 4x RDA) was associated
      with mean transport iron concentrations that were significantly higher than those
      in persons who took 0 to < or = 24 mg Fe/d. In older men, the intake of > 32 mg
      Fe/d (> 4x RDA) was associated with mean iron stores that were significantly
      higher than those in persons who took 0 to < or = 24 mg Fe/d; a similar result
      was observed in postmenopausal women, but it was of borderline statistical
      significance. CONCLUSION: Supplement users should be made aware of the amount of
      iron necessary to satisfy dietary requirements and informed of the possible
      influence that excess iron intake can have on body iron stores and health.

PMID- 16280435
TI  - Effect of a fortified maize-meal porridge on anemia, micronutrient status, and
      motor development of infants.
AB  - BACKGROUND: Maize-meal porridge is used for infant feeding in many African
      countries, including South Africa. A low-cost, finely milled, maize-meal porridge
      was fortified with beta-carotene, iron, and zinc (100% of recommended dietary
      allowance), as well as ascorbic acid, copper, selenium, riboflavin, vitamin B-6,
      vitamin B-12, and vitamin E. OBJECTIVE: We assessed whether the fortified
      porridge could reduce anemia and improve the micronutrient status and motor
      development of infants. DESIGN: Infants aged 6-12 mo (n = 361) were randomly
      assigned to receive either the fortified or unfortified porridge for 6 mo.
      Primary outcomes were hemoglobin and serum retinol, zinc, and ferritin
      concentrations and motor development. Growth was assessed as a secondary outcome.
      Primary and secondary outcomes were assessed at baseline and 6 mo. RESULTS: Two
      hundred ninety-two infants completed the study. The fortified-porridge group had
      an intervention effect of 9.4 microg/L (95% CI: 3.6, 15.1 microg/L) for serum
      ferritin and 9 g/L (95% CI: 6, 12 g/L) for hemoglobin concentrations. The
      proportion of infants with anemia decreased from 45% to 17% in the fortified
      porridge group, whereas it remained >40% in the control group. The fortified
      porridge group achieved on average 15.5 of the 25 motor development score items,
      whereas the control group achieved 14.4 items (P = 0.007). Serum retinol
      concentration showed an inconsistent effect, and no intervention effect was
      observed for serum zinc concentrations. CONCLUSIONS: This low-cost fortified
      porridge can potentially have a significant effect in reducing anemia and
      improving iron status and motor development of infants in poor settings. The
      formulation needs some adjustment in terms of zinc fortification.

PMID- 16280436
TI  - Effect of Lactobacillus GG on intestinal integrity in Malawian children at risk
      of tropical enteropathy.
AB  - BACKGROUND: Tropical enteropathy is an asymptomatic villous atrophy of the small
      bowel that is prevalent in the developing world and is associated with altered
      intestinal function and integrity. The histology of tropical enteropathy
      resembles that seen in small-bowel bacterial overgrowth. OBJECTIVE: This study
      tested the hypothesis that treatment of 3-5-y-old Malawian children with the
      probiotic Lactobacillus GG would improve their intestinal function and integrity.
      DESIGN: Clinically healthy children (n = 164) were enrolled in a placebo
      controlled, randomized, double-blind trial. Intestinal function and integrity
      were measured by using the site-specific sugar-absorption test before and after
      30 d of treatment with Lactobacillus GG or placebo. The primary outcomes were the
      ratios of urinary lactulose to mannitol (L:M) and of urinary sucrose to lactulose
      (S:L) excretion. RESULTS: Of the 161 children who completed the study, 119 (73%)
      had tropical enteropathy on enrollment (L:M > 0.10). Children receiving
      Lactobacillus GG did not differ significantly from the placebo group in the
      excretion (in % of dose administered) of mannitol (mean +/- SD: 8.9 +/- 4.4 and
      8.9 +/- 3.9, respectively), lactulose (0.31 +/- 0.20 and 0.33 +/- 0.23,
      respectively), or sucrose (0.078 +/- 0.058 and 0.082 +/- 0.075, respectively).
      L:M and S:L also did not differ significantly between the Lactobacillus and
      placebo groups (0.19 +/- 0.13 and 0.20 +/- 0.12, respectively, for L:M; 0.58 +/-
      0.46 and 0.65 +/- 0.57, respectively, for S:L). CONCLUSION: Administration of
      Lactobacillus GG for 30 d had no effect on the intestinal integrity of 3-5-y-old
      Malawian children.

PMID- 16280437
TI  - Relation between elevated serum alanine aminotransferase and metabolic syndrome
      in Korean adolescents.
AB  - BACKGROUND: Concern is growing about nonalcoholic fatty liver disease, not only
      because it is a common liver disorder but also because it is one of the leading
      causes of chronic liver disease. Unexplained elevations in aminotransferase
      concentrations have been strongly associated with adiposity and thus may
      represent nonalcoholic fatty liver disease. OBJECTIVE: We investigated the
      relation between nonviral or nonalcoholic elevations in alanine aminotransferase
      (ALT) and the metabolic syndrome in Korean adolescents. DESIGN: Data were
      obtained from 1594 subjects aged 10-19 y from the Korean National Health and
      Nutrition Examination Survey 1998, a cross-sectional health survey of a
      nationally representative sample of noninstitutionalized civilian South Koreans.
      Body mass index, waist circumference, blood pressure, fasting glucose, lipid
      profiles, and serum ALT were measured. RESULTS: The prevalence of elevated ALT (>
      40 U/L) was 3.6% in boys and 2.8% in girls. The prevalence of metabolic syndrome
      was 3.3% in both boys and girls. The components of the metabolic syndrome were
      significantly worse in the group with elevated ALT concentrations than in the
      group with normal ALT concentrations. The odds ratios (95% CIs) for elevated ALT
      were 6.6 (3.7, 11.8), 2.3 (1.2, 4.6), and 3.0 (1.6, 5.8) in the adolescents with
      abdominal obesity, high triacylglycerol concentrations, and low HDL-cholesterol
      concentrations, respectively. The odds ratios for elevated ALT were 1.5 (0.7,
      3.1), 2.6 (1.1, 6.2), and 6.2 (2.3, 16.8) in the adolescents with 1, 2, and > or
      = 3 risk factors (metabolic syndrome), respectively. CONCLUSION: The metabolic
      syndrome was strongly associated with elevated ALT concentrations in Korean
      adolescents, and this association existed in a graded fashion across the number
      of metabolic components.

PMID- 16280438
TI  - A 4-wk intervention with high intake of carotenoid-rich vegetables and fruit
      reduces plasma C-reactive protein in healthy, nonsmoking men.
AB  - BACKGROUND: Whether different intakes of vegetables and fruit modulate
      immunologic markers is currently not known. OBJECTIVE: We investigated the
      effects of low, medium, and high intakes of vegetables and fruit on markers of
      immune functions, including nonspecific markers of inflammation. DESIGN: In a
      randomized controlled trial, nonsmoking men consumed a diet that included < or =
      2 servings/d of vegetables and fruit for 4 wk. The subjects were then randomly
      assigned to 1 of 3 groups to consume 2 servings/d, 5 servings/d, or 8 servings/d
      of carotenoid-rich vegetables and fruit for another 4-wk period. Plasma
      concentrations of vitamins C and E and carotenoids were measured. The assessment
      of immunologic and inflammatory markers included the number and activity of
      natural killer cells, secretion of cytokines, lymphocyte proliferation, and
      plasma C-reactive protein concentrations. RESULTS: The high intake (8 servings/d)
      of vegetables and fruit significantly increased total carotenoid concentrations
      in plasma compared with the low intake (2 servings/d; week 4 compared with week
      8), whereas concentrations of vitamins C and E did not differ between week 4 and
      week 8. Immunologic markers were not significantly modulated. In contrast, C
      reactive protein was significantly reduced at week 8 in the subjects who consumed
      8 servings/d of vegetables and fruit compared with those who consumed 2
      servings/d. CONCLUSIONS: In healthy, well-nourished, nonsmoking men, 4 wk of low
      or high intakes of carotenoid-rich vegetables and fruit did not affect markers of
      immune function. However, a high intake of vegetables and fruit may reduce
      inflammatory processes, as indicated by the reduction of plasma C-reactive
      protein.

PMID- 16280439
TI  - Pulmonary cachexia, systemic inflammatory profile, and the interleukin 1beta -511
      single nucleotide polymorphism.
AB  - BACKGROUND: Cachexia is common in chronic obstructive pulmonary disease (COPD)
      and is thought to be linked to an enhanced systemic inflammatory response.
      OBJECTIVE: We investigated differences in the systemic inflammatory profile and
      polymorphisms in related inflammatory genes in COPD patients. DESIGN: A cross
      sectional study was performed in 99 patients with COPD (Global Initiative for
      Chronic Obstructive Lung Disease stages II-IV), who were stratified by cachexia
      based on fat-free mass index (FFMI; in kg/m2: <16 for men and <15 for women) and
      compared with healthy control subjects (HCs). Body composition was determined by
      bioelectrical impedance analysis. Plasma concentrations and gene polymorphisms of
      interleukin 1beta (IL-1beta -511), IL-6 (IL-6 -174), and the tumor necrosis
      factor system (TNF-alpha -308 and lymphotoxin-alpha +252) were determined. Plasma
      C-reactive protein, leptin, and urinary pseudouridine (as a marker of cellular
      protein breakdown) were measured. RESULTS: Fat mass, leptin, and pseudouridine
      were significantly different (P < 0.001) between noncachectic patients (NCPs) and
      cachectic patients (CPs: n = 35); the systemic inflammatory cytokine profile was
      not. NCPs had a body compositional shift toward a lower fat-free mass and a
      higher fat mass compared with HCs. CPs and NCPs had a greater systemic
      inflammatory response (P < 0.05) than did HCs, as reflected in C-reactive
      protein, soluble TNF-R75, and IL-6 concentrations. The overall distribution of
      the IL-1beta -511 polymorphism was significantly different between the groups (P
      < 0.05). CONCLUSIONS: In COPD patients, who are characterized by an elevated
      systemic inflammatory response, cachexia is not discriminatory for the extent of
      increase in inflammatory status. This study, however, indicates a potential
      influence of genetic predisposition on the cachexia process.

PMID- 16280440
TI  - Aging is associated with diminished accretion of muscle proteins after the
      ingestion of a small bolus of essential amino acids.
AB  - BACKGROUND: Previous evidence suggests that aging in healthy persons does not
      result in decreased incorporation of muscle proteins after a bolus ingestion of
      15 g essential amino acids (EAAs). OBJECTIVE: We sought to examine whether
      ingestion of a smaller bolus of EAAs is associated with diminished accretion of
      muscle proteins in the elderly when compared with the young. DESIGN: Eleven
      elderly subjects (mean +/- SEM: 68 +/- 2 y) and 8 young control subjects (mean +/
      SEM: 31 +/- 2 y) were studied in the postabsorptive state and for 3.5 h after a
      bolus ingestion of approximately 7 g EAAs. Muscle protein accretion and synthesis
      were measured with the femoral arteriovenous phenylalanine net balance technique
      during a constant infusion of L-[ring-(2)H5]phenylalanine. RESULTS: Similar to
      previous observations, no significant differences in the postabsorptive
      phenylalanine net balance were observed between the groups. However, the mean (+/
      SEM) net phenylalanine uptake after EAA ingestion was significantly less in the
      elderly (9.9 +/- 3.7 mg/leg) than in the young (25.1 +/- 3.7 mg/leg; P < 0.05).
      The mean (+/-SEM) rate of disappearance of phenylalanine during the same period
      significantly increased above basal rates in the young (36 +/- 3 compared with 30
      +/- 3 nmol x min(-1) x 100 mL leg volume(-1); P < 0.05) but not in the elderly
      (30 +/- 3 compared with 28 +/- 5 nmol x min(-1) x 100 mL leg volume(-1); P >
      0.05). CONCLUSIONS: These data indicate that aging results in a diminished
      accretion of muscle proteins after ingestion of a small dose of EAAs. These
      findings may have practical implications with respect to the amount of protein
      contained in supplements given to the elderly for enhancing the stimulation of
      muscle protein synthesis.

PMID- 16280441
TI  - Appetite assessment: simple appetite questionnaire predicts weight loss in
      community-dwelling adults and nursing home residents.
AB  - BACKGROUND: Anorexia-related weight loss can have devastating consequences on
      quality-of-life, morbidity, and mortality. Without a simple tool to evaluate
      appetite, health care providers often use inaccurate surrogates, such as
      measurement of energy consumption and nutritional risk, to reflect appetite.
      OBJECTIVE: We aimed to validate a simple tool for assessing appetite and
      predicting weight loss. DESIGN: This was a cross-sectional measurement study
      conducted on long-term care residents and community-dwelling adults. Construct
      validity of the 8-item Council on Nutrition appetite questionnaire (CNAQ) and its
      4-item derivative, the simplified nutritional appetite questionnaire (SNAQ), were
      examined through correlation with a previously validated research tool: the
      appetite hunger and sensory perception questionnaire (AHSP). The length and
      complexity of the AHSP render it inefficient for clinical use. The sensitivity
      and specificity of the CNAQ and SNAQ to predict significant weight loss were
      calculated. RESULTS: Cronbach's alpha coefficients for the CNAQ were 0.47 (long
      term care group) and 0.72 (community-dwelling group). In the long-term care
      group, the CNAQ correlated with the AHSP (r = 0.60, P < 0.001) and with the AHSP
      domains of taste (r = 0.47, P < 0.0001), hunger (r = 0.51, P < 0.0001), and smell
      (r = 0.53, P < 0.0001). The CNAQ showed sensitivities and specificities for 5%
      and 10% weight losses of 80.2 and 80.3 and 82.4 and 81.9, respectively. The SNAQ
      had sensitivities and specificities for 5% and 10% weight losses of 81.3 and 76.4
      and 88.2 and 83.5, respectively. CONCLUSIONS: The SNAQ and CNAQ are short, simple
      appetite assessment tools that predict weight loss in community-dwelling adults
      and long-term care residents. The SNAQ is a 4-item derivative of the CNAQ and
      thus is clinically more efficient.

PMID- 16280442
TI  - Effectiveness and cost-effectiveness of early screening and treatment of
      malnourished patients.
AB  - BACKGROUND: About 25-40% of hospital patients are malnourished. With current
      clinical practices, only 50% of malnourished patients are identified by the
      medical and nursing staff. OBJECTIVE: The objective of this study was to report
      the cost and effectiveness of early recognition and treatment of malnourished
      hospital patients with the use of the Short Nutritional Assessment Questionnaire
      (SNAQ). DESIGN: The intervention group consisted of 297 patients who were
      admitted to 2 mixed medical and surgical wards and who received both malnutrition
      screening at admission and standardized nutritional care. The control group
      consisted of a comparable group of 291 patients who received the usual hospital
      clinical care. Outcome measures were weight change, use of supplemental drinks,
      use of tube feeding, use of parenteral nutrition and in-between meals, number of
      consultations by the hospital dietitian, and length of hospital stay. RESULTS:
      The recognition of malnutrition improved from 50% to 80% with the use of the SNAQ
      malnutrition screening tool during admission to the hospital. The standardized
      nutritional care protocol added approximately 600 kcal and 12 g protein to the
      daily intake of malnourished patients. Early screening and treatment of
      malnourished patients reduced the length of hospital stay in malnourished
      patients with low handgrip strength (ie, frail patients). To shorten the mean
      length of hospital stay by 1 d for all malnourished patients, a mean investment
      of 76 euros (91 US dollars) in nutritional screening and treatment was needed.
      The incremental costs were comparably low in the whole group and in the subgroup
      of malnourished patients with low handgrip strength. CONCLUSIONS: Screening with
      the SNAQ and early standardized nutritional care improves the recognition of
      malnourished patients and provides the opportunity to start treatment at an early
      stage of hospitalization. The additional costs of early nutritional care are low,
      especially in frail malnourished patients.

PMID- 16280443
TI  - Effects of moderate doses of vitamin A as an adjunct to the treatment of
      pneumonia in underweight and normal-weight children: a randomized, double-blind,
      placebo-controlled trial.
AB  - BACKGROUND: Randomized controlled trials have shown inconsistent responses of
      childhood pneumonia to the use of vitamin A as an adjunct to the standard
      treatment of pneumonia. OBJECTIVE: We evaluated the effect of a moderate dose of
      vitamin A as an adjunct to standard antimicrobial treatment on the duration of
      respiratory signs in children with pneumonia. DESIGN: Children, aged 2-59 mo,
      with pneumonia and weight-for-age <50th percentile who had been admitted to the
      Baca Ortiz Children's Hospital in Quito, Ecuador, were randomly assigned to
      receive 50,000 IU (aged 2-12 mo) or 100,000 IU (aged >12-59 mo) vitamin A or a
      placebo. RESULTS: Of the 287 children enrolled, 145 received vitamin A and 142
      received placebo. No overall differences were observed between the 2 groups in
      the duration of signs of pneumonia. Multiple linear regression showed a
      significant interaction between basal serum retinol concentration and vitamin A
      group for the time (in h) to remission of respiratory signs (beta = -3.57, SE =
      1.09, P = 0.001). Duration of clinical signs was less in children with basal
      serum retinol concentrations >200 microg/L who received vitamin A supplements
      than in children with similar concentrations who received placebo (69.9 +/- 49.9
      h compared with 131.3 +/- 143.9 h; P = 0.049). CONCLUSIONS: Overall, we found no
      effect of a moderate dose of vitamin A supplementation on the duration of
      uncomplicated pneumonia in underweight or normal-weight children aged <5 y.
      However, a beneficial effect was seen in children with high basal serum retinol
      concentrations.

PMID- 16280444
TI  - Two ethnic-specific polymorphisms in the human Agouti-related protein gene are
      associated with macronutrient intake.
AB  - BACKGROUND: The Agouti-related protein (AGRP), an appetite modulator, induces
      hyperphagia when administered intracerebroventricularly or when overexpressed in
      transgenic mice. Exogenous administration of AGRP in rodents predisposes to high
      fat and high sugar intakes. OBJECTIVE: The objective was to examine the potential
      associations of 2 ethnic-specific polymorphisms in the AGRP gene (Ala67Thr in
      whites and -38C>T in blacks) in the Health, Risk Factors, Exercise Training, and
      Genetics (HERITAGE) Family Study. DESIGN: We examined the effect of the 2
      polymorphisms in the AGRP gene on self-reported macronutrient intakes in 478
      white and 272 black participants in the HERITAGE Family Study. RESULTS: Both AGRP
      polymorphisms showed a significant association with energy intake. In whites, a
      smaller proportion of total energy was derived from fat by the Ala67Thr
      heterozygotes (mean +/- SEM: 29.4 +/- 0.7%) than by the Ala67Ala homozygotes
      (31.5 +/- 0.5%; P = 0.009), mainly because of a lower intake of saturated (P =
      0.06) and monounsaturated (P = 0.01) fats by the Ala67Thr heterozygotes. The
      percentage of energy from carbohydrates was 2.6% greater in the Ala67Thr
      heterozygotes (55.1 +/- 1.1%) than in the Ala67Ala homozygotes (52.5 +/- 0.6%; P
      = 0.03). In blacks, protein intake was associated with the -38C>T promoter
      polymorphism. T/T homozygotes had a significantly lower protein intake than did
      the C-allele carriers (C/C: 16.8 +/- 0.4%; C/T: 17.2 +/- 0.2%; T/T: 15.4 +/-
      0.7%; P = 0.04). No significant differences in total energy and alcohol intakes
      existed between genotype groups in blacks or whites. CONCLUSIONS: The present
      study suggests that 2 ethnic-specific AGRP variants, previously shown to be
      associated with leanness in the HERITAGE Family Study, are also associated with
      macronutrient intake.

PMID- 16280445
TI  - Effect of ferroportin Q248H polymorphism on iron status in African children.
AB  - BACKGROUND: Iron deficiency is common in African children, but genetic variations
      affecting susceptibility have not been identified. The Q248H mutation in
      ferroportin, a cellular iron exporter regulated by iron status and inflammation,
      may be associated with high iron stores in African adults. OBJECTIVE: The study
      examined the prevalence of iron deficiency in African children in an area where
      malaria transmission is low to absent and investigated whether ferroportin Q248H
      provides protection from iron deficiency. DESIGN: Complete blood counts, serum
      markers of iron status and inflammation, and ferroportin Q247H were measured in
      208 preschool children in Harare, Zimbabwe. Iron deficiency was defined by serum
      ferritin and C-reactive protein (CRP) concentrations (definition 1) or by
      ferritin and the ratio of transferrin receptor to log10 ferritin (definition 2).
      RESULTS: Q248H was present in 40 children (38 heterozygotes, 2 homozygotes),
      elevated CRP was present in 26 (12.5%), and iron deficiency was present in 50
      (24.0%) (definition 1) or 55 (26.4%) (definition 2). The interaction between
      ferroportin Q248H and CRP was significant for ferritin concentrations (P = 0.027)
      in a 2-factor analysis of variance model. With elevated CRP, the estimated
      geometric mean (SE range) ferritin concentration was 74 (52-106) microg/L for
      Q248H heterozygotes but 24 (20-30) microg/L for wild-type subjects (P = 0.016).
      With normal CRP, the ferritin concentration was 16 (14-19) microg/L whether or
      not the mutation was present. After adjustment for age and weight-for-height z
      score, the odds ratio (OR) for iron deficiency in Q248H heterozygotes was not
      significant according to definition 1 (OR: 0.53; 95% CI: 0.18, 1.40; P = 0.222)
      or definition 2 (OR: 0.39; 95% CI: 0.14, 1.07; P = 0.068). CONCLUSIONS: Any
      effect of Q248H in protecting against iron deficiency may be observable in
      children exposed to repeated inflammatory conditions. Further studies of iron
      status and ferroportin Q248H in African children are needed.

PMID- 16280446
TI  - Long-term protein intake and dietary potential renal acid load are associated
      with bone modeling and remodeling at the proximal radius in healthy children.
AB  - BACKGROUND: Protein and alkalizing minerals are increasingly described as playing
      a major role in influencing bone status, not only in the elderly but also in
      children and adolescents. OBJECTIVE: We examined whether the long-term dietary
      protein intake and diet net acid load are associated with bone status in
      children. DESIGN: In a prospective study design in 229 healthy children and
      adolescents aged 6-18 y, long-term dietary intakes were calculated from 3-d
      weighed dietary records that were collected yearly over the 4-y period before a
      one-time bone analysis. Dietary acid load was characterized as potential renal
      acid load (PRAL) by using an algorithm including dietary protein, phosphorus,
      magnesium, and potassium. Proximal forearm bone variables were measured by
      peripheral quantitative computed tomography. RESULTS: After adjustment for age,
      sex, and energy intake and control for forearm muscularity, BMI, growth velocity,
      and pubertal development, we observed that long-term dietary protein intake was
      significantly positively associated with periosteal circumference (P < 0.01),
      which reflected bone modeling, and with cortical area (P < 0.001), bone mineral
      content (P < 0.01), and polar strength strain index (P < 0.0001), which reflected
      a combination of modeling and remodeling. Children with a higher dietary PRAL had
      significantly less cortical area (P < 0.05) and bone mineral content (P < 0.01).
      Long-term calcium intake had no significant effect on any bone variable.
      CONCLUSIONS: Long-term dietary protein intake appears to act anabolically on
      diaphyseal bone strength during growth, and this may be negated, at least partly,
      if dietary PRAL is high, ie, if the intake of alkalizing minerals is low.

PMID- 16280447
TI  - Effects of calcium, dairy product, and vitamin D supplementation on bone mass
      accrual and body composition in 10-12-y-old girls: a 2-y randomized trial.
AB  - BACKGROUND: Little is known about the relative effectiveness of calcium
      supplementation from food or pills with or without vitamin D supplementation for
      bone mass accrual during the rapid growth period. OBJECTIVE: The purpose was to
      examine the effects of both food-based and pill supplements of calcium and
      vitamin D on bone mass and body composition in girls aged 10-12 y. DESIGN: This
      placebo-controlled intervention trial randomly assigned 195 healthy girls at
      Tanner stage I-II, aged 10-12 y, with dietary calcium intakes <900 mg/d to 1 of 4
      groups: calcium (1000 mg) + vitamin D3 (200 IU), calcium (1000 mg), cheese (1000
      mg calcium), and placebo. Primary outcomes were bone indexes of the hip, spine,
      and whole body by dual-energy X-ray absorptiometry and of the radius and tibia by
      peripheral quantitative computed tomography. RESULTS: With the use of intention
      to-treat or efficacy analysis, calcium supplementation with cheese resulted in a
      higher percentage change in cortical thickness of the tibia than did placebo,
      calcium, or calcium + vitamin D treatment (P = 0.01, 0.038, and 0.004,
      respectively) and in higher whole-body bone mineral density than did placebo
      treatment (P = 0.044) when compliance was >50%. With the use of a hierarchical
      linear model with random effects to control for growth velocity, these
      differences disappeared. CONCLUSIONS: Increasing calcium intake by consuming
      cheese appears to be more beneficial for cortical bone mass accrual than the
      consumption of tablets containing a similar amount of calcium. Diverse patterns
      of growth velocity may mask the efficacy of supplementation in a short-term trial
      of children transiting through puberty.

PMID- 16280448
TI  - Nutrition, mild hyperparathyroidism, and bone mineral density in young Japanese
      women.
AB  - BACKGROUND: The adverse effects of poor nutrition on the bones of young Asian
      women have not been fully elucidated. OBJECTIVE: The purpose of this study was to
      investigate possible associations of vitamin D nutrition, calcium intake, and
      other nutrients with bone metabolism and bone mass in young Japanese women.
      DESIGN: The subjects were 108 female college students aged 19-25 y. Dietary
      nutrients were measured by using the duplicate sampling method on 3 weekdays.
      Serum 25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone, and bone
      turnover markers were also measured. Bone mineral density (BMD) of the spine and
      femur was measured by dual-energy X-ray absorptiometry. RESULTS: The proportions
      of the subjects with low 25(OH)D (< 30 nmol/L) and high intact parathyroid
      hormone (> or = 6.9 pmol/L) concentrations were 32.4% and 15.7%, respectively.
      Serum 25(OH)D concentrations (P = 0.0265) and calcium intake (P = 0.0103) were
      inversely associated with serum intact parathyroid hormone. In addition to weight
      and physical activity, the presence of mild hyperparathyroidism was associated
      with a low BMD of the lumbar spine (P = 0.0062) and the femoral neck (P =
      0.0250), and a low calcium intake was associated with a low BMD of the femoral
      neck (P = 0.0044). CONCLUSIONS: Low calcium intake (based on low BMD of the
      femoral neck only) and mild hyperparathyroidism (based on low BMD of both the
      femoral neck and lumbar spine), partly explained by low vitamin D nutrition and a
      low calcium intake, are important predictors of low BMD in young Japanese women.
      Effects of poor nutrition and mild hyperparathyroidism on bone peak bone mass in
      young women should be further investigated in longitudinal studies.

PMID- 16280449
TI  - Waist circumference gain compared with waist circumference as predictors of type
      2 diabetes risk.

PMID- 16280450
TI  - Utility of the relative-dose-response and modified-relative-dose-response tests
      as population indicators of vitamin A status.

PMID- 16280451
TI  - Validity of the dose-response tests for the determination of vitamin A status.

PMID- 16280452
TI  - How justifiable is it to distort the energy profile of a diet to obtain benefits
      in body weight control?

PMID- 16280453
TI  - Potential harm of vitamin E supplementation.

PMID- 16280454
TI  - Structural elucidation of human oxidative metabolites of muraglitazar: use of
      microbial bioreactors in the biosynthesis of metabolite standards.
AB  - Muraglitazar (Pargluva), a dual alpha/gamma peroxisome proliferator-activated
      receptor activator, is currently in clinical development for treatment of type 2
      diabetes. This study describes the structural elucidation of the human oxidative
      metabolites of muraglitazar through the use of a combination of microbial
      bioreactors, NMR and accurate mass analyses, and organic synthesis. Plasma,
      urine, and feces were collected from six healthy subjects following oral
      administration of 14C-labeled muraglitazar (10 mg, 100 microCi) and pooled
      samples were analyzed. Approximately 96% of the recovered radioactive dose was
      found in the feces and 3.5% in the urine. The parent compound represented >85% of
      the radioactivity in plasma. The fecal radioactivity was distributed among 16
      metabolites (M1-M12, M14-M16, and M8a) and the parent drug, of which
      hydroxylation and O-demethylation metabolites (M5, M10, M11, M14, and M15)
      represented the prominent human metabolites. The urinary radioactivity was
      distributed into several peaks including muraglitazar glucuronide (M13) and the
      parent drug. Low concentrations of metabolites in human samples prevented direct
      identification of metabolites beyond liquid chromatographic (LC)-mass
      spectrometric analysis. Microbial strains Cunninghamella elegans and
      Saccharopolyspora hirsuta produced muraglitazar metabolites that had the same
      high performance liquid chromatography retention times and the same tandem mass
      spectrometric (MS/MS) properties as the corresponding human metabolites. The
      microbial metabolites M9, M10, M11, M14, M15, and M16 were isolated and analyzed
      by NMR. Based on these LC-MS/MS and NMR analyses, and organic synthesis, the
      structures of 16 human oxidative metabolites were identified. The oxidative
      metabolism of muraglitazar was characterized by hydroxylation, O-demethylation,
      oxazolering opening, and O-demethylation/hydroxylation, as well as O-dealkylation
      and carboxylic acid formation. This study demonstrated the utility of microbial
      bioreactors for the identification of metabolites.

PMID- 16280455
TI  - Metabolism of the psychotomimetic tryptamine derivative 5-methoxy-N,N
      diisopropyltryptamine in humans: identification and quantification of its urinary
      metabolites.
AB  - The urinary metabolites of 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) in
      humans have been investigated by analyzing urine specimens from its users. For
      the unequivocal identification and accurate quantification of its major
      metabolites, careful analyses were conducted by gas chromatography/mass
      spectrometry, liquid chromatography/mass spectrometry, and liquid chromatography
      tandem mass spectrometry, using authentic standards of each metabolite
      synthesized. Three major metabolic pathways were revealed as follows: 1) side
      chain degradation by O-demethylation to form 5-hydroxy-N,N-diisopropyltryptamine
      (5-OH-DIPT), which would be partly conjugated to its sulfate and glucuronide; 2)
      direct hydroxylation on position 6 of the aromatic ring of 5-MeO-DIPT, and/or
      methylation of the hydroxyl group on position 5 after hydroxylation on position 6
      of the aromatic ring of 5-OH-DIPT, to produce 6-hydroxy-5-methoxy-N,N
      diisopropyltryptamine (6-OH-5-MeO-DIPT), followed by conjugation to its sulfate
      and glucuronide; and 3) side chain degradation by N-deisopropylation, to the
      corresponding secondary amine 5-methoxy-N-isopropyltryptamine (5-MeO-NIPT). Of
      these metabolites, which retain structural characteristics of the parent drug, 5
      OH-DIPT and 6-OH-5-MeO-DIPT were found to be more abundant than 5-MeO-NIPT.
      Although the parent drug 5-MeO-DIPT was detectable even 35 h after dosing, no
      trace of its N-oxide was detected in any of the specimens examined.

PMID- 16280456
TI  - Inhibition of lung cancer cell growth by quercetin glucuronides via G2/M arrest
      and induction of apoptosis.
AB  - Lung cancer is the leading cause of cancer death in many developed countries,
      including Taiwan. Quercetin, a widely distributed bioflavonoid, is well known to
      induce growth inhibition in a variety of human cancer cells. Quercetin
      glucuronides are the main circulating metabolites after dietary supplements with
      quercetin in humans. However, there is little information available as to how
      quercetin glucuronides affect human cancer cells. We investigated the effects of
      quercetin glucuronides in a human lung cancer cell line NCI-H209. We checked the
      cell viability, cell cycle checkpoint proteins, pro- and antiapoptotic proteins,
      caspase-3 activity, and gene expression by flow cytometry and Western blot. The
      viability of cells decreased in a dose- and time-dependent manner. Cell cycle
      analysis revealed a significant increase of the proportion of cells in G2/M phase
      and subG0/G1 phase (corresponding to apoptotic cells). Moreover, quercetin
      glucuronides increased the expressions of cyclin B, Cdc25c-ser-216-p, and Wee1
      proteins, indicating the G2/M arrest. We also demonstrated a concurrent decrease
      of the mitochondrial membrane potential, release of cytochrome c, up-regulation
      of Bax, down-regulation of Bcl-2, and activation of caspase-3, and subsequently,
      cleavage of poly(ADP-ribose) polymerase. In addition, quercetin glucuronide
      induced apoptosis was totally blocked by the broad-spectrum caspase inhibitor
      benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone. Taken together, we demonstrated
      that quercetin glucuronides inhibited proliferation through G2/M arrest of the
      cell cycle and induced apoptosis via caspase-3 cascade in the human lung cancer
      cell line NCI-H209. Delineation of the biological effects of specific major
      quercetin metabolites on chemotherapeutic potential or chemoprevention of human
      cancers warrants further investigation.

PMID- 16280458
TI  - The importance of maturational studies in airway smooth muscle.

PMID- 16280459
TI  - Effect of p47phox gene deletion on ROS production and oxygen sensing in mouse
      carotid body chemoreceptor cells.
AB  - Membrane potential in oxygen-sensitive type I cells in carotid body is controlled
      by diverse sets of voltage-dependent and -independent K(+) channels. Coupling of
      Po(2) to the open-closed state of channels may involve production of reactive
      oxygen species (ROS) by NADPH oxidase. One hypothesis suggests that ROS are
      produced in proportion to the prevailing Po(2) and a subset of K(+) channels
      closes as ROS levels decrease. We evaluated ROS levels in normal and p47(phox)
      gene-deleted [NADPH oxidase knockout (KO)] type I cells using the ROS-sensitive
      dye dihydroethidium (DHE). In normal cells, hypoxia elicited an increase in ROS,
      which was blocked by the specific NADPH oxidase inhibitor 4-(2-aminoethyl)
      benzenesulfonyl fluoride (AEBSF, 3 mM). KO type I cells did not respond to
      hypoxia, but the mitochondrial uncoupler azide (5 microM) elicited increased
      fluorescence in both normal and KO cells. Hypoxia had no effect on ROS production
      in sensory and sympathetic neurons. Methodological control experiments showed
      that stimulation of neutrophils with a cocktail containing the chemotactic
      peptide N-formyl-Met-Leu-Phe (1 microM), arachidonic acid (10 microM), and
      cytochalasin B (5 microg/ml) elicited a rapid increase in DHE fluorescence. This
      response was blocked by the NADPH oxidase inhibitor diphenyleneiodonium (10
      microM). KO neutrophils did not respond; however, azide (5 microM) elicited a
      rapid increase in fluorescence. Physiological studies in type I cells
      demonstrated that hypoxia evoked an enhanced depression of K+ current and
      increased intracellular Ca2+ levels in KO vs. normal cells. Moreover, AEBSF
      potentiated hypoxia-induced increases in intracellular Ca2+ and enhanced the
      depression of K+ current in low O(2). Our findings suggest that local
      compartmental increases in oxidase activity and ROS production inhibit the
      activity of type I cells by facilitating K+ channel activity in hypoxia.

PMID- 16280460
TI  - Activation of endothelial NADPH oxidase during normoxic lung ischemia is KATP
      channel dependent.
AB  - Previous studies have shown endothelial cell membrane depolarization and
      generation of reactive oxygen species (ROS) in endothelial cells with abrupt
      reduction in shear stress (ischemia). This study evaluated the role of ATP
      sensitive potassium (K(ATP)) channels and NADPH oxidase in the ischemic response
      by using Kir6.2-/- and gp91(phox)-/- mice. To evaluate ROS generation, we
      subjected isolated perfused mouse lungs labeled with 2',7'
      dichlorodihydrofluorescein (DCF), hydroethidine (HE), or diphenyl-1
      pyrenylphosphine (DPPP) to control perfusion followed by global ischemia. In wild
      type C57BL/6J mice, imaging of subpleural endothelial cells showed a time
      dependent increase in intensity for all three fluorescence probes with ischemia,
      which was blocked by preperfusion with cromakalim (a K(ATP) channel agonist) or
      diphenyleneiodonium (DPI, a flavoprotein inhibitor). Endothelial cell
      fluorescence with bis-oxonol, a membrane potential probe, increased during lung
      ischemia indicating cell membrane depolarization. The change in membrane
      potential with ischemia in lungs of gp91(phox)-/- mice was similar to wild type,
      but ROS generation did not occur. Lungs from Kir6.2-/- showed marked attenuation
      of the change in both membrane potential and ROS production. Thus membrane
      depolarization during lung ischemia requires the presence of a K(ATP) channel and
      is required for activation of NADPH oxidase and endothelial ROS generation.

PMID- 16280462
TI  - A unifying explanation of primary generalized seizures through nonlinear brain
      modeling and bifurcation analysis.
AB  - The aim of this paper is to explain critical features of the human primary
      generalized epilepsies by investigating the dynamical bifurcations of a nonlinear
      model of the brain's mean field dynamics. The model treats the cortex as a medium
      for the propagation of waves of electrical activity, incorporating key
      physiological processes such as propagation delays, membrane physiology, and
      corticothalamic feedback. Previous analyses have demonstrated its descriptive
      validity in a wide range of healthy states and yielded specific predictions with
      regards to seizure phenomena. We show that mapping the structure of the nonlinear
      bifurcation set predicts a number of crucial dynamic processes, including the
      onset of periodic and chaotic dynamics as well as multistability. Quantitative
      study of electrophysiological data supports the validity of these predictions.
      Hence, we argue that the core electrophysiological and cognitive differences
      between tonic-clonic and absence seizures are predicted and interrelated by the
      global bifurcation diagram of the model's dynamics. The present study is the
      first to present a unifying explanation of these generalized seizures using the
      bifurcation analysis of a dynamical model of the brain.

PMID- 16280461
TI  - Voice recognition and cross-modal responses to familiar speakers' voices in
      prosopagnosia.
AB  - Recognizing the voices of people we know does not only activate "voice areas" in
      the temporal lobe but also extraauditory areas including the fusiform "face area"
      (FFA). This cross-modal effect could reflect that individual face and voice
      information become specifically associated when becoming acquainted with a
      person. Here, we addressed whether the ability to have individual face
      representations 1) plays a role in voice recognition and 2) is required to
      observe cross-modal responses to voices in face areas. We compared speaker
      recognition performance and neuroimaging responses during the processing of
      familiar and nonfamiliar speakers' voices in a developmental prosopagnosic
      subject (SO) with the respective findings obtained in a group of 9 control
      subjects. Despite scoring worse than controls on recognition of familiar
      speakers' voices, SO had normal cross-modal responses in the FFA and normal
      connectivity between FFA and the voice regions. However, she had reduced
      activations in areas that usually respond to familiarity with people. An
      indication for the malfunctioning of her FFA was reduced connectivity of the FFA
      to a subset of these supramodal areas. In combination these data suggest that 1)
      voice recognition benefits from the ability to process faces at an individual
      level and 2) cross-modal association of voices and faces in the brain is achieved
      by a sensory binding and does not depend on a top-down mechanism subsequent to
      successful person recognition.

PMID- 16280463
TI  - Brain processing of the signals ascending through unmyelinated C fibers in
      humans: an event-related functional magnetic resonance imaging study.
AB  - Event-related functional magnetic resonance imaging was used to investigate brain
      processing of the signals ascending from peripheral C and Adelta fibers evoked by
      phasic laser stimuli on the right hand in humans. The stimulation of both C and
      Adelta nociceptors activated the bilateral thalamus, bilateral secondary
      somatosensory cortex, right (ipsilateral) middle insula, and bilateral Brodmann's
      area (BA) 24/32, with the majority of activity found in the posterior portion of
      the anterior cingulate cortex (ACC). However, magnitude of activity in the right
      (ipsilateral) BA32/8/6, including dorsal parts in the anterior portion of the ACC
      (aACC) and pre-supplementary motor area (pre-SMA), and the bilateral anterior
      insula was significantly stronger following the stimulation of C nociceptors than
      Adelta nociceptors. It was concluded that the activation of C nociceptors,
      related to second pain, evokes different brain processing from that of Adelta
      nociceptors, related to first pain, probably due to the differences in the
      emotional and motivational aspects of either pain, which are mainly related to
      the aACC, pre-SMA, and anterior insula.

PMID- 16280464
TI  - Structural brain changes in tinnitus.
AB  - Tinnitus is a common but poorly understood disorder characterized by ringing or
      buzzing in the ear. Central mechanisms must play a crucial role in generating
      this auditory phantom sensation as it persists in most cases after severing the
      auditory nerve. One hypothesis states that tinnitus is caused by a reorganization
      of tonotopic maps in the auditory cortex, which leads to an overrepresentation of
      tinnitus frequencies. Moreover, the participation of the limbic system in
      generating tinnitus has been postulated. Here we aimed at identifying brain areas
      that display structural change in tinnitus. We compared tinnitus sufferers with
      healthy controls by using high-resolution magnetic resonance imaging and voxel
      based morphometry. Within the auditory pathways, we found gray-matter increases
      only at the thalamic level. Outside the auditory system, gray-matter decrease was
      found in the subcallosal region including the nucleus accumbens. Our results
      suggest that reciprocal involvement of both sensory and emotional areas are
      essential in the generation of tinnitus.

PMID- 16280465
TI  - Hemispheric specialization for processing auditory nonspeech stimuli.
AB  - The left hemisphere specialization for speech perception might arise from
      asymmetries at more basic levels of auditory processing. In particular, it has
      been suggested that differences in "temporal" and "spectral" processing exist
      between the hemispheres. Here we used functional magnetic resonance imaging to
      test this hypothesis further. Fourteen healthy volunteers listened to sequences
      of alternating pure tones that varied in the temporal and spectral domains.
      Increased temporal variation was associated with activation in Heschl's gyrus
      (HG) bilaterally, whereas increased spectral variation activated the superior
      temporal gyrus (STG) bilaterally and right posterior superior temporal sulcus
      (STS). Responses to increased temporal variation were lateralized to the left
      hemisphere; this left lateralization was greater in posteromedial HG, which is
      presumed to correspond to the primary auditory cortex. Responses to increased
      spectral variation were lateralized to the right hemisphere specifically in the
      anterior STG and posterior STS. These findings are consistent with the notion
      that the hemispheres are differentially specialized for processing auditory
      stimuli even in the absence of linguistic information.

PMID- 16280466
TI  - Novel mechanism of P-fimbriated Escherichia coli virulence in pyelonephritis.

PMID- 16280467
TI  - Race and kidney disease outcomes: genes or environment?

PMID- 16280468
TI  - Observational research databases in renal disease.
AB  - Observational, patient-oriented research is a term that describes clinical or
      community-based studies in that they do not involve an experiment or
      intervention. Observational research studies can be designed and implemented by a
      primary data collection or using previously collected patient data. The latter is
      less expensive, although it has some distinct limitations. Many research
      databases are readily available and can be used to answer important questions
      that are relevant to kidney disease. This review summarizes the types of research
      analyses that can be conducted using existing databases, the types of research
      databases available, and a general approach for addressing a proposed research
      question using existing data.

PMID- 16280469
TI  - Toll-like receptor-7 modulates immune complex glomerulonephritis.
AB  - Viral infections may trigger immune complex glomerulonephritis via Toll-like
      receptors (TLR), as certain TLR trigger immunity upon recognition of viral
      nucleic acids. On the basis of previous findings regarding viral double-stranded
      RNA and TLR3 in experimental lupus erythematosus, a similar role for TLR7 that
      recognizes viral single-stranded RNA was hypothesized. Immunostaining of kidney
      sections of nephritic MRLlpr/lpr mice revealed TLR7 expression in infiltrating ER
      HR3-positive macrophages and few CD11c-positive dendritic cells but not in
      glomerular mesangial cells as observed for TLR3. This finding was consistent with
      the distribution pattern of intravenously injected single-stranded RNA in
      nephritic MRLlpr/lpr mice. TLR7 ligation activated monocytes and dendritic cells,
      both isolated from MRLlpr/lpr mice, to secrete IFN-alpha, IL-12p70, IL-6, and
      CCL2. In vivo, a single injection of the TLR7 ligand imiquimod increased serum
      levels of IL-12p70, IFN-alpha, and IL-6. A course of 25 microg of imiquimod given
      every other day from week 16 to 18 of age aggravated lupus nephritis in
      MRLlpr/lpr mice. This was associated with increased glomerular immune complex
      deposits as well as interstitial expression of CCL2 in imiquimod-treated
      MRLlpr/lpr mice. Different types of viral nucleic acids seem to modulate systemic
      autoimmunity through specific interactions with their respective TLR. Different
      TLR expression profiles on immune cell subsets and nonimmune parenchymal cell
      types determine the molecular mechanisms involved in viral infection-associated
      exacerbation of lupus nephritis and possibly other types of immune complex
      glomerulonephritis.

PMID- 16280470
TI  - Type IV collagen induces podocytic features in bone marrow stromal stem cells in
      vitro.
AB  - Bone marrow-derived stromal stem cells (BMSC) can differentiate along a variety
      of mesenchymal lines, including mesangial cells. For determining whether BMSC can
      be induced to differentiate along podocytic lines in vitro, canine BMSC were
      cultured on plastic, type I collagen, and NC1 hexamers of type IV collagen from
      normal and Alport canine glomerular basement membrane. Results were compared with
      a mouse podocyte cell line. In the case of the podocyte line, differentiation
      occurred on all three matrices as indicated by the expression of synaptopodin and
      CD2-associated protein (CD2AP) and organization of myosin heavy chain IIA into a
      linear pattern. BMSC proliferated equally well on all matrices, but cells that
      were grown on type IV collagen NC1 hexamers became larger and stellate. Evidence
      for podocytic differentiation occurred on all three collagen matrices as
      indicated by the redistribution of myosin IIA to a linear pattern and expression
      of synaptopodin, CD2AP, and alpha-actinin. A punctate distribution of CD2AP was
      seen only in cells that were grown on normal and Alport glomerular basement
      membrane NC1 hexamers. Differentiated podocytes expressed the alpha1, alpha2, and
      alpha5 chains of type IV collagen but at higher levels in cells that were grown
      on NC1 hexamers. Similar results were obtained in BMSC for the alpha1 and alpha2
      chains only. The alpha3, alpha4, and alpha6 chains were never detected in the
      podocyte line or BMSC. These results indicate that BMSC undergo a degree of
      podocytic differentiation in vitro and greater when grown on type IV collagen NC1
      hexamers than type I collagen. Alport and normal NC1 hexamers seem equally
      permissive to BMSC growth and differentiation, suggesting that these processes
      are not influenced specifically by the alpha3/alpha4/alpha5 network. BMSC may be
      useful in the development of stem cell-based reconstitution of glomeruli that are
      damaged by disease and for gene therapy of genetic glomerular diseases such as
      Alport syndrome.

PMID- 16280471
TI  - Left ventricular geometry in children with mild to moderate chronic renal
      insufficiency.
AB  - Left ventricular hypertrophy (LVH) is the most important independent marker of
      cardiovascular risk in adults with chronic kidney disease. Cardiovascular
      morbidity seems increased even in children with chronic renal insufficiency
      (CRI), but the age and stage of CRI when cardiac alterations become manifest are
      unknown. For assessing the prevalence and factors associated with abnormal LV
      geometry in children with CRI, echocardiograms, ambulatory BP monitoring, and
      biochemical profiles were obtained in 156 children aged 3 to 18 yr with stages 2
      through 4 chronic kidney disease (GFR 49 +/- 19 ml/min per 1.73 m2) and compared
      with echocardiograms obtained in 133 healthy children of comparable age and
      gender. LV mass was indexed to height2.7. Concentric LV remodeling was observed
      in 10.2%, concentric LVH in 12.1%, and eccentric LVH in 21% of patients. LVH was
      more common in boys (43.3 versus 19.4%; P < 0.005). Probability of LVH
      independently increased with male gender (odds ratio [OR] 2.62; P < 0.05) and
      standardized body mass index (OR 1.56; P = 0.01). Low hemoglobin, low GFR, young
      age, and high body mass index were independent correlates of LV mass index (0.005
      < P < 0.05). LV concentricity (relative wall thickness) was positively associated
      with serum albumin (P < 0.05). Probability of abnormal LV geometry increased with
      C-reactive protein >10 mg/dl (OR 26; P < 0.001). In conclusion, substantial
      cardiac remodeling of both concentric and eccentric type is present at young age
      and early stages of CRI in children. Prevalence of LVH is related to male gender,
      anemia, and ponderosity but not to BP. Additional effects of volume status and
      inflammation on cardiac geometry are also evident.

PMID- 16280472
TI  - Plasma osteoprotegerin is associated with mortality in hemodialysis patients.
AB  - Expression of bone proteins resulting from transdifferentiation of vascular
      smooth muscle cells into osteoblasts suggests that vascular calcifications are a
      bioactive process. Regulating molecules such as osteoprotegerin (OPG) and
      receptor activator of NF-kappaB ligand (RANKL) could play a key role in bone
      vascular calcification imbalance. This study investigated the contribution of
      these proteins as well as mineral metabolism disorders in hemodialysis (HD)
      patient outcome. A total of 185 HD patients were followed up prospectively for 2
      yr. In addition to clinical characteristics, mineral metabolism markers as well
      as OPG and soluble RANKL (sRANKL) were measured at baseline. After 2 yr, survival
      rates were described with Kaplan-Meier and compared with Cox regression analyses;
      50 patients died (27 from cardiovascular diseases). Calcium, phosphate, and
      calcium x phosphate product were not associated with mortality. Both
      hyperparathyroidism (parathyroid hormone > or =300 pg/ml) and hypoparathyroidism
      (parathyroid hormone <150 pg/ml) were poorly associated with all-cause and
      cardiovascular mortality. By contrast, elevated OPG levels predicted all-cause
      (relative risk [RR] 2.67; 95% confidence interval [CI] 1.32 to 5.41; P = 0.006)
      and cardiovascular mortality (RR 3.15; 95% CI 1.14 to 8.69; P = 0.03). Low levels
      of sRANKL were associated with a protective effect for all-cause mortality (RR
      0.45; 95% CI 0.21 to 0.94; P = 0.03). The association of OPG with all-cause
      mortality was stronger in patients with C-reactive protein > or =12.52 mg/L. In
      this condition, both highest (RR 5.68; 95% CI 1.48 to 22.73; P = 0.01) and lowest
      tertiles (RR 5.37; 95% CI 147 to 1968; P = 0.01) significantly predicted poor
      outcome. These results show that regulating-bone molecules, especially OPG, are
      strong predictors of mortality in HD patients, suggesting that OPG is a vascular
      risk factor, in particular in patients who have high C-reactive protein levels.
      OPG determination therefore should be added to the biologic follow-up of these
      patients.

PMID- 16280476
TI  - Changes ahead for IJSEM in 2006.

PMID- 16280477
TI  - The preparation of the approved lists of bacterial names.

PMID- 16280473
TI  - Skin autofluorescence, a measure of cumulative metabolic stress and advanced
      glycation end products, predicts mortality in hemodialysis patients.
AB  - Tissue advanced glycation end products (AGE) are a measure of cumulative
      metabolic stress and trigger cytokines driven inflammatory reactions. AGE are
      thought to contribute to the chronic complications of diabetes and ESRD. Tissue
      autofluorescence is related to the accumulation of AGE. Therefore, skin
      autofluorescence (AF) may provide prognostic information on mortality in
      hemodialysis (HD) patients. Skin AF was measured noninvasively with an AF reader
      at baseline in 109 HD patients. Overall and cardiovascular mortality was
      monitored prospectively during a period of 3 yr. The AF reader was validated
      against AGE contents in skin biopsies from 29 dialysis patients. Forty-two of the
      109 (38.5%) HD patients died. Cox regression analysis showed that AF was an
      independent predictor of overall and cardiovascular mortality (for overall
      mortality odds ratio [OR] 3.9), as were pre-existing cardiovascular disease (CVD;
      OR 3.1), C-reactive protein (OR 1.1), and serum albumin (OR 0.3). Multivariate
      analysis revealed that 65% of the variance in AF could be attributed to the
      independent effects of age, dialysis and renal failure duration, presence of
      diabetes, triglycerides levels, and C-reactive protein. AF was also independently
      linked to the presence of CVD at baseline (OR 8.8; P < 0.001). AF correlated with
      collagen-linked fluorescence (r = 0.71, P < 0.001), pentosidine (r = 0.75, P <
      0.001), and carboxy(m)ethyllysine (both r = 0.45, P < 0.01). Skin AF is a strong
      and independent predictor of mortality in ESRD. This supports a role for AGE as a
      contributor to mortality and CVD and warrants interventions specifically aimed at
      AGE accumulation.

PMID- 16280478
TI  - Vibrio gigantis sp. nov., isolated from the haemolymph of cultured oysters
      (Crassostrea gigas).
AB  - Polyphasic analysis of four new Vibrio isolates originating from the haemolymph
      of diseased cultured oysters is described. The new isolates were closely related
      to Vibrio splendidus, having 98 % 16S rRNA gene sequence similarity. Phylogenetic
      analysis based on DNA gyrase subunit B (gyrB), RNA polymerase sigma70 factor
      (rpoD), replication origin-binding protein (rctB) and transmembrane regulatory
      protein (toxR) genes, fluorescent amplified fragment length polymorphism and DNA
      DNA hybridization experiments clearly showed that the new isolates form a tight
      genomic group that is different from the currently known Vibrio species. It is
      proposed that these new isolates should be accommodated in a novel species,
      Vibrio gigantis sp. nov. Phenotypic features that differentiate V. gigantis from
      other known Vibrio species include arginine dihydrolase, gelatinase and beta
      galactosidase activities, NO(2) production, growth at 35 degrees C, and
      utilization of sucrose, melibiose, amygdalin, glycerol, galactose, starch and
      glycogen. The type strain is LGP 13T (=LMG 22741T=CIP 108656T).

PMID- 16280479
TI  - Proteiniphilum acetatigenes gen. nov., sp. nov., from a UASB reactor treating
      brewery wastewater.
AB  - Two proteolytic, strictly anaerobic bacterial strains (TB107(T) and TB6-6) were
      isolated from the granule sludge of an upflow anaerobic sludge blanket reactor
      treating brewery wastewater. The strains were Gram-negative, non-spore-forming
      and motile. Cells were rod-shaped (0.6-0.9x1.9-2.2 microm). Growth of the strains
      was observed at 20-45 degrees C and pH 6.0-9.7. The strains were proteolytic.
      Yeast extract, peptone, pyruvate, glycine and l-arginine could be used as carbon
      and energy sources. Weak growth was also observed with tryptone, l-serine, l
      threonine and l-alanine as carbon and energy sources. Both strains did not use
      any of the tested carbohydrates, alcohols and fatty acids except pyruvate. Acetic
      acid and NH3 were produced from yeast extract, peptone and l-arginine, and
      propionic acid was also produced from yeast extract. Pyruvate was converted to
      acetic acid and CO2. Gelatin was not hydrolysed. Indole and H2S were not
      produced. The two strains did not grow in medium containing 20 % bile. Addition
      of strain TB107T to a syntrophic propionate-degrading co-culture accelerated the
      propionate-degradation rate. The predominant cellular fatty acid was the branched
      chain fatty acid anteiso-C(15 : 0) (46.21 %). The genomic DNA G+C contents of
      strains TB107T and TB6-6 were 46.6 and 48.9 mol%, respectively. Phylogenetic
      analysis based on 16S rRNA gene sequences revealed that the two strains represent
      a new phyletic sublineage within the Cytophaga-Flavobacterium-Bacteroides (CFB)
      group, with <91 % 16S rRNA gene sequence similarity to the closest species with
      validly published names. On the basis of polyphasic evidence from this study, a
      new genus and species, Proteiniphilum acetatigenes gen. nov., sp. nov., is
      proposed, with strain TB107T (=JCM 12891T=AS 1.5024T) as the type strain.

PMID- 16280481
TI  - Suttonella ornithocola sp. nov., from birds of the tit families, and emended
      description of the genus Suttonella.
AB  - Phenotypic and phylogenetic studies were performed on three strains of Gram
      negative, rod-shaped organisms recovered from dead birds of the tit families
      (blue tit, coal tit and long-tailed tit). Morphological, cultural and biochemical
      studies indicated that the organisms were related to the family
      Cardiobacteriaceae in the gamma-subclass of the Proteobacteria. Comparative 16S
      rRNA gene sequencing studies confirmed these findings and demonstrated that the
      bacterium represents a hitherto unknown subline within this family. The closest
      phylogenetic relative of the strains isolated from the birds was found to be
      Suttonella indologenes, although a sequence divergence of approximately 5 %
      demonstrated that the unknown bacterium represented a novel species. On the basis
      of the results of the phylogenetic analysis and phenotypic criteria, it is
      proposed that the bacteria recovered from the diseased birds represent a novel
      species, Suttonella ornithocola sp. nov., with strain B6/99/2T (=CCUG 49457T=NCTC
      13337T) as the type strain.

PMID- 16280480
TI  - Sulfurihydrogenibium yellowstonense sp. nov., an extremely thermophilic,
      facultatively heterotrophic, sulfur-oxidizing bacterium from Yellowstone National
      Park, and emended descriptions of the genus Sulfurihydrogenibium,
      Sulfurihydrogenibium subterraneum and Sulfurihydrogenibium azorense.
AB  - A novel thermophilic, sulfur-oxidizing Gram-negative bacterium, designated strain
      SS-5T, was isolated from the Calcite Hot Springs in Yellowstone National Park,
      USA. The cells were motile rods (1.2-2.8 microm long and 0.6-0.8 microm wide).
      The new isolate was a facultative heterotroph capable of using elemental sulfur
      or thiosulfate as an electron donor and O2 (1-18 %; optimum 6 %, v/v) as an
      electron acceptor. Hydrogen did not support growth. The isolate grew
      autotrophically with CO2. In addition, strain SS-5T utilized various organic
      carbon sources such as yeast extract, tryptone, sugars, amino acids and organic
      acids. Growth was observed between 55 and 78 degrees C (optimum 70 degrees C; 3.5
      h doubling time), pH 6.0 and 8.0 (optimum pH 7.5), and 0 and 0.6 % (w/v) NaCl
      (optimum 0 %). The G+C content of the genomic DNA was 32 mol%. Phylogenetic
      analysis based on the 16S rRNA gene sequence indicated that the isolate was a
      member of the genus Sulfurihydrogenibium. On the basis of the physiological and
      molecular characteristics of the new isolate, we propose the name
      Sulfurihydrogenibium yellowstonense sp. nov. with SS-5T (=JCM 12773T=OCM 840T) as
      the type strain. In addition, emended descriptions of the genus
      Sulfurihydrogenibium, Sulfurihydrogenibium subterraneum and Sulfurihydrogenibium
      azorense are proposed.

PMID- 16280482
TI  - Nitrincola lacisaponensis gen. nov., sp. nov., a novel alkaliphilic bacterium
      isolated from an alkaline, saline lake.
AB  - A novel alkaliphilic bacterium, strain 4CAT, was isolated from decomposing wood
      taken from the shore of Soap Lake, a saline, alkaline lake in Grant County, WA,
      USA. Cells of the isolate were Gram-negative, asporogenous, short, motile rods
      that utilized only a limited range of organic acids as sole carbon and energy
      sources. In addition to oxygen, the strain possessed the ability to reduce in the
      presence of acetate. Strain 4CAT was oxidase- and catalase-positive; it degraded
      Tween 60, but not DNA, urea, gelatin or starch. It grew at pH values from 7.5 to
      11.0, with optimum growth occurring at pH 9.0, and growth was observed in NaCl
      concentrations of 0.2-1.3 M, with optimum growth at 0.8 M NaCl. The optimum
      temperature for growth was 37 degrees C. Strain 4CAT was resistant to
      erythromycin, bacitracin, novobiocin, polymyxin B, neomycin, gentamicin,
      streptomycin, carbenicillin, rifampicin and tetracycline, and was susceptible to
      nalidixic acid, chloramphenicol, ampicillin and penicillin. The isolate's 16S
      rRNA gene sequence indicated that it belonged to the gamma-Proteobacteria,
      showing 90-94 % similarity to its closest relatives. Maximum-likelihood
      phylogenetic inferences placed strain 4CAT within a novel lineage related to the
      marine bacterial genera Neptunomonas and Marinobacterium. The DNA G+C content of
      the isolate was 47.4 mol%. On the basis of genotypic and phenotypic
      characterization, it was concluded that strain 4CAT should be placed in a
      separate taxon as a novel genus and species, with the proposed name Nitrincola
      lacisaponensis gen. nov., sp. nov. The type strain is 4CAT (=ATCC BAA-920T=DSM
      16316T).

PMID- 16280483
TI  - Nonlabens tegetincola gen. nov., sp. nov., a novel member of the family
      Flavobacteriaceae isolated from a microbial mat in a subtropical estuary.
AB  - An orange-pigmented, Gram-negative, non-motile, rod-shaped, strictly aerobic
      bacterium (UST030701-324T) was isolated from a microbial mat in an estuary in the
      Bahamas. The DNA G+C content was 33.6 mol%. Predominant fatty acids were i15 : 0,
      i16 : 0, i17 : 0 3-OH, and summed feature 3, comprising i15 : 0 2-OH and/or 16 :
      1omega7c. MK-6 was the only respiratory quinone. Flexirubin-type pigments were
      not produced. Phylogenetic analysis based on 16S rRNA gene sequences placed
      UST030701-324T in a distinct lineage in the family Flavobacteriaceae with less
      than 90.7 % sequence similarity to the members of the nearest genus,
      Psychroflexus. UST030701-324T can be distinguished from other members of
      Flavobacteriaceae by a number of chemotaxonomic and phenotypic characteristics.
      It is thus proposed that UST030701-324T represents a novel taxon designated
      Nonlabens tegetincola gen. nov., sp. nov. The type strain is UST030701-324T
      (=NRRL B-41136T=JCM 12886T).

PMID- 16280484
TI  - Luteibacter rhizovicinus gen. nov., sp. nov., a yellow-pigmented
      gammaproteobacterium isolated from the rhizosphere of barley (Hordeum vulgare
      L.).
AB  - Three strains of Gram-negative, aerobic, yellow-pigmented, chemo-organotrophic
      bacteria, motile by a polar flagellum, were isolated from the rhizosphere of
      spring barley (Hordeum vulgare L.) at a research field near Copenhagen, Denmark.
      The three strains, LJ79, LJ96T and LJ99, formed visible colonies on one-tenth
      strength tryptic soy broth supplemented with agar (1/10 TSBA) after incubation
      for 6 days at 15 degrees C. The strains hydrolysed starch, casein (skimmed milk),
      gelatin and various pentoses and hexoses and grew on MacConkey agar and full
      strength TSBA. Growth on 1/10 TSBA occurred at 4-30 degrees C, pH 6-9 and 0-3 %
      (w/v) NaCl. The strains had identical 16S rRNA gene sequences and ERIC
      (enterobacterial repetitive intergenic consensus sequence) fingerprint profiles,
      but could be differentiated by their RAPD (random amplified polymorphic DNA)
      fingerprint patterns. Strain LJ96(T) had a DNA G+C content of 64.3 mol% and the
      major fatty acids were 15 : 0 iso (23.4 %), 17 : 1 iso omega9c (25.5 %) and 17 :
      0 iso (18.1 %). Phylogenetic analysis of the 16S rRNA gene sequences of the three
      strains showed 96 % sequence similarity to Rhodanobacter lindaniclasticus LMG
      18385T, 95 % to Frateuria aurantia DSM 6220T and 96 % to Fulvimonas soli LMG
      19981T. Using LJ96T DNA as probe, DNA-DNA hybridizations documented the
      relationship of the three strains to a single species (87.4-98.7 % relatedness)
      and showed less than 30 % relatedness to Frateuria aurantia DSM 6220T and
      Fulvimonas soli DSM 14263T. Rhodanobacter lindaniclasticus LMG 18385T is not
      extant and the strain not available from any public strain collections, thus DNA
      DNA hybridization could not include this strain. On the basis of genotypic and
      phenotypic characteristics, the three yellow-pigmented strains could also be
      differentiated from Frateuria aurantia, Fulvimonas soli and Rhodanobacter
      lindaniclasticus. The name Luteibacter rhizovicinus gen. nov., sp. nov. is
      proposed, with the type strain LJ96T (=DSM 16549T=ATCC BAA-1015T).

PMID- 16280485
TI  - Photobacterium aplysiae sp. nov., a lipolytic marine bacterium isolated from eggs
      of the sea hare Aplysia kurodai.
AB  - A bacterium, named GMD509T, showing lipolytic activity was isolated from the eggs
      of the sea hare Aplysia kurodai collected at Mogiyeo (depth, 12 m), an
      uninhabited small island in the South Sea of Korea. The strain is Gram-negative,
      motile, facultatively anaerobic, mesophilic and weakly halophilic. Optimal growth
      of strain GMD509T occurs in the presence of 3.0 % (w/v) NaCl and at pH 8 and 25
      degrees C. The whole-cell fatty acid profile of the isolate includes C16 : 1, C16
      : 0 and C18 : 1 as major fatty acids and its DNA G+C content is 45 mol%.
      Phylogenetic analyses of 16S rRNA gene sequences place this bacterium in the
      gamma-Proteobacteria, within the genus Photobacterium. The 16S rRNA gene sequence
      of strain GMD509T is most similar to those of Photobacterium frigidiphilum (97.8
      %), Photobacterium profundum (97.5 %) and Photobacterium indicum (97.4 %). DNA
      DNA relatedness levels between the isolate and its closest known phylogenetic
      relatives, P. frigidiphilum and P. indicum, are 25.3 and 13.7 %, respectively.
      Strain GMD509T therefore represents a novel species, for which the name
      Photobacterium aplysiae sp. nov. is proposed, with the type strain GMD509T (=KCTC
      12383T=JCM 12948T).

PMID- 16280487
TI  - Marinomonas dokdonensis sp. nov., isolated from sea water.
AB  - Two Gram-negative, motile, non-spore-forming, slightly halophilic bacteria
      (strains DSW10-10T and DSW10-19) were isolated from sea water and subjected to a
      polyphasic taxonomic study. They grew optimally at 30 degrees C and in the
      presence of 2-3 % (w/v) NaCl. Strains DSW10-10T and DSW10-19 were characterized
      chemotaxonomically as containing Q-8 as the predominant ubiquinone and C18 : 17c,
      C16 : 0 and C16 : 17c and/or iso-C15 : 0 2-OH as the major fatty acids. Their DNA
      G+C contents were 45 x 3-45 x 7 mol%. Strains DSW10-10T and DSW10-19 exhibited a
      16S rRNA gene sequence similarity value of 100 % and possessed a mean DNA-DNA
      relatedness level of 85 %. Phylogenetic analyses based on 16S rRNA gene sequences
      showed that strains DSW10-10T and DSW10-19 fell within the radiation of the
      cluster encompassed by the genus Marinomonas. Strains DSW10-10T and DSW10-19 had
      16S rRNA gene sequence similarity levels of 95 x 7-97 x 7 % with respect to the
      type strains of Marinomonas species with validly published names. Levels of DNA
      DNA relatedness were low enough to indicate that the two strains constitute a
      distinct Marinomonas species. On the basis of phenotypic data and phylogenetic
      and genetic distinctiveness, strains DSW10-10T (=KCTC 12394T=DSM 17202T) and
      DSW10-19 were placed in the genus Marinomonas as members of a novel species,
      Marinomonas dokdonensis sp. nov.

PMID- 16280486
TI  - Leadbetterella byssophila gen. nov., sp. nov., isolated from cotton-waste
      composts for the cultivation of oyster mushroom.
AB  - A bacterial strain, designated 4M15T, was isolated from cotton-waste composts
      used as mushroom cultivation in South Korea. Properties of this isolate were
      studied on the basis of physiological and biochemical characteristics, fatty acid
      profile, isoprenoid quinone, DNA G+C content and phylogenetic position based on
      16S rRNA gene sequence analysis. The strain was found to form a distinct
      phylogenetic lineage related to the family 'Flexibacteraceae' within the phylum
      'Bacteroidetes'. No recognized species showed >85 % 16S rRNA gene sequence
      similarity to strain 4M15T. The fatty acid profile of strain 4M15(T) included
      C(16 : 1)omega7c/iso-C(15 : 0) 2-OH (30.5 %), iso-C(15 : 0) (24.2 %), iso-C(15 :
      0) 2-OH/C(16 : 1)omega7c (15.9), iso-C(17 : 0) 3-OH (10.5 %) and C(16 : 0) (5.6
      %). The major isoprenoid quinone was menaquinone MK-7. The DNA G+C content was
      33.0 mol%. Cells were Gram-negative, strictly aerobic, rod-shaped, non-motile,
      catalase-positive, oxidase-positive and flexirubin-positive. The strain
      hydrolysed aesculin, gelatin, starch and tyrosine. Several phenotypic tests could
      be used to differentiate strain 4M15T from other members of the family
      'Flexibacteraceae'. On the basis of the data presented, strain 4M15T should be
      assigned to the phylum 'Bacteroidetes' as a novel genus and species, for which
      the name Leadbetterella byssophila gen. nov., sp. nov. is proposed. The type
      strain is 4M15T (=KACC 11308T=DSM 17132T).

PMID- 16280488
TI  - Characterization of alkaliphilic Bacillus strains used in industry: proposal of
      five novel species.
AB  - Twenty alkaliphilic bacterial strains from industrial applications or enzyme
      studies were subjected to a polyphasic taxonomic investigation, including 16S
      rRNA gene sequencing, determination of genomic DNA G+C content, DNA-DNA
      hybridization, fatty acid analysis and standard bacteriological characterization.
      By comparing the groupings obtained based on the genomic DNA G+C content and the
      construction of a phylogenetic tree based on the 16S rRNA gene sequence, 12
      clusters of similar strains were recognized. DNA-DNA hybridization revealed that
      these clusters represented five novel genospecies. Further analysis supported the
      proposal of five novel species in the genus Bacillus: Bacillus wakoensis sp. nov.
      (type strain N-1T=JCM 9140T=DSM 2521T), Bacillus hemicellulosilyticus sp. nov.
      (type strain C-11T=JCM 9152T=DSM 16731T), Bacillus cellulosilyticus sp. nov.
      (type strain N-4T=JCM 9156T=DSM 2522T), Bacillus akibai sp. nov. (type strain
      1139T=JCM 9157T=ATCC 43226T) and Bacillus mannanilyticus sp. nov. (type strain AM
      001T=JCM 10596T=DSM 16130T).

PMID- 16280489
TI  - Spiroplasma penaei sp. nov., associated with mortalities in Penaeus vannamei,
      Pacific white shrimp.
AB  - A new bacterial strain, designated SHRIMP(T), isolated from the haemolymph of the
      Pacific white shrimp, Penaeus vannamei, was serologically distinct from other
      spiroplasmas. Cells of this strain were helical in form and variable in length.
      Examination by electron microscopy revealed wall-less cells delineated by a
      single cytoplasmic membrane. The organisms grew well in M1D media supplemented
      with 2 % NaCl. Strain SHRIMP(T) grew at temperatures of 20-37 degrees C, with
      optimum growth occurring at 28 degrees C. The strain catabolized glucose and
      hydrolysed arginine, but did not hydrolyse urea. The G+C content of the DNA was
      29 +/-1 mol%. Strain SHRIMP(T) (=ATCC BAA-1082T=CAIM 1252T) is designated the
      type strain of a novel species, Spiroplasma penaei sp. nov., which represents a
      new subgroup (I-9) of the group I spiroplasmas.

PMID- 16280490
TI  - Dokdonia donghaensis gen. nov., sp. nov., isolated from sea water.
AB  - Two Gram-negative, non-motile, non-spore-forming, slightly halophilic bacterial
      strains, DSW-1T and DSW-21, were isolated from sea water and subjected to a
      polyphasic taxonomic study. They grew optimally at 30 degrees C and in the
      presence of 2 % (w/v) NaCl. Strains DSW-1T and DSW-21 were characterized
      chemotaxonomically as containing MK-6 as the predominant menaquinone and iso-C15
      : 0, iso-C17 : 0 3-OH and iso-C15 : 1 as the major fatty acids. Their DNA G+C
      content was 38 mol%. Strains DSW-1T and DSW-21 exhibited four nucleotide
      differences in their 16S rRNA gene sequences and possessed a mean DNA-DNA
      relatedness level of 78 %. Phylogenetic analyses based on 16S rRNA gene sequences
      revealed that strains DSW-1T and DSW-21 formed a distinct lineage within the
      family Flavobacteriaceae. The 16S rRNA gene sequences of strains DSW-1T and DSW
      21 had similarity levels of less than 92 x 2 % to the sequences of other members
      of the family Flavobacteriaceae. There were some differences in phenotypic
      properties between the two strains and Cellulophaga species, the nearest
      phylogenetic neighbours. On the basis of phenotypic, phylogenetic and genetic
      data, strains DSW-1T (=KCTC 12391T=DSM 17200T) and DSW-21 were classified in a
      novel genus and species, Dokdonia donghaensis gen. nov., sp. nov.

PMID- 16280491
TI  - Silvimonas terrae gen. nov., sp. nov., a novel chitin-degrading facultative
      anaerobe belonging to the 'Betaproteobacteria'.
AB  - A taxonomic study was carried out on a bacterial strain, designated KM-45T,
      isolated from forest soil collected near Daejeon, South Korea. Comparative 16S
      rRNA gene sequence analysis indicated a clear affiliation of this bacterium to
      the 'Betaproteobacteria' and that it was related most closely to Chitinibacter
      tainanensis BCRC 17254T, Formivibrio citricus DSM 6150T and Iodobacter
      fluviatilis ATCC 33051T (92.4, 91.2 and 88.9 % 16S rRNA gene sequence similarity,
      respectively). Cells were Gram-negative, facultatively anaerobic, motile and rod
      shaped. The strain grew well on R2A medium and utilized a broad spectrum of
      carbon sources. The G+C content of the genomic DNA was 58 mol% and the
      predominant ubiquinone was Q-8. Major fatty acids were C(16 : 0), C(16 :
      1)omega7c/iso-C(15 : 0) 2-OH, C(18 : 1)omega7c/omega9t/omega12t and C(17 : 0)
      cyclo. On the basis of the evidence presented, it is proposed that strain KM-45T
      should be placed in a novel genus and species, for which the name Silvimonas
      terrae gen. nov., sp. nov. is proposed. The type strain is KM-45T (=KCTC
      12358T=NBRC 100961T).

PMID- 16280492
TI  - Methylobacterium isbiliense sp. nov., isolated from the drinking water system of
      Sevilla, Spain.
AB  - Three pink-pigmented facultatively methylotrophic bacteria were isolated from
      drinking water. These strains (designated AR24T, AR25 and GR32) have been
      characterized on the basis of phenotypic traits, 16S rRNA gene sequence analysis
      and DNA-DNA hybridization. According to the results of these analyses, the three
      strains belong to the genus Methylobacterium. Analysis of 16S rRNA gene sequences
      revealed that the three isolates constituted a single phylogenetic group. The
      level of 16S rRNA gene sequence similarities with respect to the type strains of
      the genus Methylobacterium were less than 96.5 %, except for the type strain of
      Methylobacterium nodulans (98.1 %). The G+C content of their DNA ranged from 69.0
      to 69.7 mol%. DNA-DNA hybridization values confirmed that they constitute a novel
      species for which we propose the name Methylobacterium isbiliense sp. nov. The
      type strain is AR24T (=CECT 7068T=CCM 7304T).

PMID- 16280493
TI  - Paenibacillus alkaliterrae sp. nov., isolated from an alkaline soil in Korea.
AB  - A Gram-positive, rod-shaped, motile and endospore-forming bacterial strain, KSL
      134T, was isolated from an alkaline soil in Korea, and its taxonomic position was
      investigated by a polyphasic study. Strain KSL-134T grew optimally at pH 7 x 5
      and 30 degrees C. Its cell wall peptidoglycan contained meso-diaminopimelic acid.
      Strain KSL-134T was characterized as having MK-7 as the predominant menaquinone
      and anteiso-C15 : 0 as the major fatty acid. The DNA G+C content was 49 x 4 mol%.
      Phylogenetic analyses based on 16S rRNA gene sequences showed that strain KSL
      134T formed a distinct lineage within the evolutionary radiation encompassed by
      the genus Paenibacillus. Similarity levels between the 16S rRNA gene sequence of
      strain KSL-134T and those of the type strains of recognized Paenibacillus species
      ranged from 90 x 4 to 96 x 5 %. DNA-DNA relatedness levels and some differential
      phenotypic properties were enough to distinguish strain KSL-134T from several
      phylogenetically related Paenibacillus species. On the basis of phenotypic and
      phylogenetic data, strain KSL-134T (=KCTC 3956T=DSM 17040T) was classified in the
      genus Paenibacillus as a member of a novel species, for which the name
      Paenibacillus alkaliterrae sp. nov. is proposed.

PMID- 16280494
TI  - Methylosarcina lacus sp. nov., a methanotroph from Lake Washington, Seattle, USA,
      and emended description of the genus Methylosarcina.
AB  - An obligately methanotrophic bacterial strain, LW14T, isolated from the sediment
      of Lake Washington, Seattle, USA, is described taxonomically. The isolate is an
      aerobic, Gram-negative, non-motile bacterium capable of growth on methane, and
      possesses type I intracytoplasmic membranes (i.e. it is a type I methanotroph).
      The strain possesses particulate methane monooxygenase (MMO) and has no soluble
      MMO. Formaldehyde is assimilated via the ribulose monophosphate cycle. The
      isolate grows within a pH range of 4-8, with the optimum between pH 5.5 and 6.5.
      The cellular fatty acid profile is dominated by C(16 : )omega18c, C(16 :
      1)omega7c and C(16 : 1)omega5t fatty acids. The DNA G+C content is 53.3+/-0.4
      mol%. On the basis of sequence analysis of the 16S rRNA gene, isolate LW14T is
      related most closely to representatives of the genus Methylosarcina. However, DNA
      DNA hybridization analysis reveals only a distant relationship between isolate
      LW14T and the previously described Methylosarcina species. On the basis of its
      phenotypic and genotypic characteristics, LW14T represents a novel species of the
      genus Methylosarcina, for which the name Methylosarcina lacus sp. nov. is
      proposed, with LW14T (=ATCC BAA-1047T=JCM 13284T) as the type strain.

PMID- 16280495
TI  - Paenibacillus mendelii sp. nov., from surface-sterilized seeds of Pisum sativum
      L.
AB  - A Gram-variable, facultatively anaerobic, endospore-forming bacterium was
      isolated from surface-sterilized seeds of the garden pea and characterized with
      phenotypic and molecular methods. A PCR with the Paenibacillus-specific primer
      PAEN515F and the 16S rRNA gene sequence indicated that strain C/2T belongs to the
      genus Paenibacillus and is closely related to Paenibacillus phyllosphaerae (94.0
      % sequence similarity). Strain C/2T generated a unique phenotypic profile, in
      particular for the production of acid from substrates. The DNA G+C content (50.8
      mol%) and the major fatty acid (anteiso-C(15 : 0)) are consistent with the genus
      Paenibacillus. DNA-DNA hybridization distinguished strain C/2T from other
      phylogenetically related Paenibacillus species and, therefore, strain C/2T (=CCM
      4839T=LMG 23002T) is here described as the type strain of a novel species, for
      which the name Paenibacillus mendelii sp. nov. is proposed.

PMID- 16280496
TI  - Shewanella pneumatophori sp. nov., an eicosapentaenoic acid-producing marine
      bacterium isolated from the intestines of Pacific mackerel (Pneumatophorus
      japonicus).
AB  - An eicosapentaenoic acid-producing bacterium, previously described as Shewanella
      sp. strain SCRC-2738, was classified by phenotypic characterization,
      chemotaxonomic analysis, 16S rRNA gene sequence analysis and DNA-DNA
      hybridization. The isolate was Gram-negative, rod-shaped and motile by using
      polar flagella. The strain grew at 4-32 degrees C; the optimum growth temperature
      was 27 degrees C. NaCl was required for growth. The major isoprenoid quinones
      were ubiquinone-7 and ubiquinone-8 and its DNA G+C content was 42.8 mol%. The
      whole-cell fatty acids mainly (above 5 %) consisted of iso-C(13 : 0), iso-C(15 :
      0), C(16 : 0), C(16 : 1)omega7c, C(18 : 1)omega7c and C(20 : 5)omega3
      (eicosapentaenoic acid). Phylogenetic analysis based on the 16S rRNA gene
      sequence showed that strain SCRC-2738T was related closely (sequence similarities
      above 99 %) to Shewanella marinintestina (99.3 %), Shewanella sairae (99.3 %) and
      Shewanella schlegeliana (99.2 %). DNA-DNA hybridization and phenotypic
      characteristics confirmed that strain SCRC-2738T merited classification as a
      novel species of the genus Shewanella, for which the name Shewanella
      pneumatophori sp. nov. is proposed. The type strain is SCRC-2738T (=JCM
      13187T=NCIMB 14060T).

PMID- 16280497
TI  - Sphingomonas yunnanensis sp. nov., a novel gram-negative bacterium from a
      contaminated plate.
AB  - A Gram-negative bacterium, YIM 003T, which was isolated from a contaminated plate
      in the laboratory, was subjected to a polyphasic taxonomic study. The organism
      had short-rod-shaped, motile cells, formed yellow-pigmented colonies on ISP2
      medium and its optimum growth pH was 7.0-7.5. The major respiratory lipoquinone
      was ubiquinone Q-10. The phosphate-containing lipids detected in strain YIM 003T
      were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylcholine, sphingoglycolipid and one unidentified phospholipid. The
      major fatty acids were C(18 : 1)omega7c (59.8 %), C(16 : 0) (9.9 %), ai-C(17 : 0)
      (5.3 %), i-C(17 : 0) (4.4 %) and C(14 : 0) 2-OH (15.8 %). The G+C content of the
      genomic DNA was 67.5 mol%. Strain YIM 003T exhibited levels of 16S rRNA gene
      sequence similarity of 98.2 % to Sphingomonas phyllosphaerae FA2T and 98.0 % to
      Sphingomonas adhaesiva DSM 7418T but showed less than 97.0 % similarity with
      respect to other species with validly published names. The DNA-DNA relatedness
      values of the isolate with S. phyllosphaerae FA2T and S. adhaesiva DSM 7418T were
      59 and 26 %, respectively. The phenotypic characteristics and genotypic data
      indicate that strain YIM 003T should be distinguished from S. phyllosphaerae FA2T
      and S. adhaesiva DSM 7418T. Therefore, on the basis of the polyphasic taxonomic
      data presented, a novel species of the genus Sphingomonas, Sphingomonas
      yunnanensis sp. nov., is proposed, with the type strain YIM 003T (=CCTCC AB
      204064T=KCTC 12346T).

PMID- 16280498
TI  - Description of Gluconacetobacter swingsii sp. nov. and Gluconacetobacter
      rhaeticus sp. nov., isolated from Italian apple fruit.
AB  - Two Gram-negative, rod-shaped, non-spore-forming bacteria (DST GL01T and DST
      GL02T) were isolated from apple fruit juice in the region of the Italian Alps. On
      the basis of 16S rRNA gene sequence similarities, strains DST GL01T and DST GL02T
      were shown to belong to the alpha-subclass of the Proteobacteria, and, in
      particular, to the genus Gluconacetobacter, in the Gluconacetobacter xylinus
      branch (98.5-100 %). Chemotaxonomic data (major ubiquinone, Q10; predominant
      fatty acid, C(18 : 1omega7c), accounting for approximately 50 % of the fatty acid
      content) support the affiliation of both strains to the genus Gluconacetobacter.
      The results of DNA-DNA hybridizations, together with physiological and
      biochemical data, allowed genotypic and phenotypic differentiation between
      strains DST GL01T and DST GL02T and from the 11 validly published
      Gluconacetobacter species. They therefore represent two new species, for which
      the names Gluconacetobacter swingsii sp. nov. and Gluconacetobacter rhaeticus sp.
      nov. are proposed, with the type strains DST GL01T (=LMG 22125T=DSM 16373T) and
      DST GL02T (=LMG 22126T=DSM 16663T), respectively.

PMID- 16280499
TI  - Thalassobius mediterraneus gen. nov., sp. nov., and reclassification of Ruegeria
      gelatinovorans as Thalassobius gelatinovorus comb. nov.
AB  - A Gram-negative, slightly halophilic, non-pigmented, strictly aerobic, chemo
      organotrophic bacterium was isolated from sea water off the western Mediterranean
      coast near Valencia (Spain). This strain was able to grow on several organic
      acids and amino acids added to a minimal medium as carbon sources, but used few
      carbohydrates or yielded slight growth when sugars were used. Phylogenetic
      analysis based on an almost complete 16S rRNA gene sequence revealed that strain
      XSM19T was a member of the Roseobacter group within the 'Alphaproteobacteria',
      with its closest phylogenetic neighbour being Ruegeria gelatinovorans (97.6 %
      sequence similarity). Following a polyphasic approach, it was concluded that
      strain XSM19T represents a new genus and novel species, for which the name
      Thalassobius mediterraneus sp. nov. is proposed. The type strain is XSM19T (=CECT
      5383T=CIP 108400T=CCUG 49438T). It is also proposed that R. gelatinovorans (Ruger
      & Hofle 1992) Uchino et al. 1999 is reclassified as Thalassobius gelatinovorus
      comb. nov.

PMID- 16280500
TI  - Roseovarius mucosus sp. nov., a member of the Roseobacter clade with trace
      amounts of bacteriochlorophyll a.
AB  - Among a group of marine isolates that were found to be positive for genes of the
      bacterial photosynthetic reaction centre, a strain was selected for
      characterization that was phylogenetically close to the genus Roseovarius. The
      strain, designated DFL-24T, originated from a culture of Alexandrium ostenfeldii
      (dinoflagellate) and contained small amounts of bacteriochlorophyll a,
      corresponding to about 1 % of the amount found in intensely pigmented aerobic
      phototrophs such as Roseobacter litoralis. Cells were rods of 0.5-0.7x1.3-3.0
      microm often with uneven ends, suggesting a budding mode of division. True
      motility was not observed. Electron micrographs of ultrathin sections revealed a
      Gram-negative cell-wall structure. Cultures did not grow without addition of sea
      salts and tolerated up to 10 % (w/v) sea-water salts. Acetate, butyrate,
      tricarboxylic acid cycle intermediates, glutamate and glycerol were used as
      growth substrates, but not glucose or fructose. Biotin, thiamine and nicotinic
      acid were required as growth factors. The DNA G+C content was 63 mol%. 16S rRNA
      gene sequence analysis placed the strain within the Roseobacter lineage of the
      'Alphaproteobacteria'. Its closest phylogenetic neighbour was Roseovarius
      tolerans showing 96.4 % 16S rRNA gene sequence similarity. Based also on its
      physiological and biochemical characteristics, the strain is considered to
      represent a novel species of the genus Roseovarius, Roseovarius mucosus sp. nov.
      Strain DFL-24T (=DSM 17069T=NCIMB 14077T) is the type strain. The 16S rRNA gene
      sequence of DFL-24T was found to have a similarity of 99.7 % with an unidentified
      strain, 253-13 (=DSM 17070), which was likewise characterized and shown to
      constitute another strain of the species.

PMID- 16280501
TI  - Alteromonas hispanica sp. nov., a polyunsaturated-fatty-acid-producing,
      halophilic bacterium isolated from Fuente de Piedra, southern Spain.
AB  - Strain F-32T, which produces exopolysaccharides and contains polyunsaturated
      fatty acids, was isolated from a hypersaline water sample collected from Fuente
      de Piedra (southern Spain). Phylogenetic analyses indicated conclusively that the
      strain in question belonged to the genus Alteromonas. Phenotypic tests showed
      that it could be assigned to the genus Alteromonas although it had a number of
      distinctive characteristics: it is moderately halophilic, growing best with 7.5
      10 % w/v NaCl; it grows at 4 degrees C and produces H2S; it does not grow with d
      cellobiose, d-fructose, d-galactose, d-glucose or lactose as sole sources of
      carbon and energy; and its fatty-acid profile is typical of Alteromonas but it
      also contains a large amount of an unusual acid with three double bonds [18 :
      3omega6c (6, 9, 12); 5.01 %, w/v]. The major isoprenoid quinone is Q8. The DNA
      G+C content is 46.3 mol%. The phylogenetic, phenotypic and genetic properties of
      strain F-32T place it within a novel species, for which the name Alteromonas
      hispanica sp. nov. is proposed. The type strain is F-32T (=CECT 7067T=LMG
      22958T).

PMID- 16280502
TI  - Cyclobacterium amurskyense sp. nov., a novel marine bacterium isolated from sea
      water.
AB  - The taxonomic position of a novel marine, heterotrophic, aerobic, pigmented, non
      motile bacterium isolated from sea water was determined. 16S rRNA gene sequence
      analysis revealed that strain KMM 6143T is a member of the genus Cyclobacterium.
      The results of DNA-DNA hybridization experiments supported by phenotypic and
      chemotaxonomic data showed that the isolate represents a novel species of the
      genus Cyclobacterium, for which the name Cyclobacterium amurskyense sp. nov. is
      proposed. The type strain is KMM 6143T (=KCTC 12363T=LMG 23026T).

PMID- 16280503
TI  - Alkalibacillus filiformis sp. nov., isolated from a mineral pool in Campania,
      Italy.
AB  - A halo-alkaliphilic, Gram-positive, non-motile bacterium, designated strain 4AGT,
      was isolated from a mineral pool located in Malvizza, Campania, southern Italy.
      On the basis of 16S rRNA gene sequence analysis, strain 4AGT was shown to belong
      to the genus Alkalibacillus within the phylum Firmicutes; its phylogenetic
      distance from recognized Alkalibacillus species was <95.0 %. Chemotaxonomic data
      (MK-7 as the major menaquinone; directly cross-linked meso-diaminopimelic acid in
      the cell wall; phosphatidylglycerol and diphosphatidylglycerol as major polar
      lipids; iso-C(15 : 0), anteiso-C(15 : 0) and iso-C(17 : 0) as major fatty acids;
      and glycine betaine and glutamate as major compatible solutes) supported the
      affiliation of the strain to the genus Alkalibacillus. The results of DNA-DNA
      hybridization and physiological and biochemical tests allowed genotypic and
      phenotypic differentiation of strain 4AGT from the two recognized Alkalibacillus
      species. Strain 4AGT therefore represents a novel species, for which the name
      Alkalibacillus filiformis sp. nov. is proposed. The type strain is 4AGT (=DSM
      15448T=ATCC BAA-956T).

PMID- 16280504
TI  - Conserved indels in protein sequences that are characteristic of the phylum
      Actinobacteria.
AB  - Gram-positive bacteria with a high G+C content are currently recognized as a
      distinct phylum, Actinobacteria, on the basis of their branching in 16S rRNA
      trees. Except for an insert in the 23S rRNA, there are no unique biochemical or
      molecular characteristics known at present that can distinguish this group from
      all other bacteria. In this work, three conserved indels (i.e. inserts or
      deletions) are described in three widely distributed proteins that are
      distinctive characteristics of the Actinobacteria and are not found in any other
      groups of bacteria. The identified signatures are a 2 aa deletion in cytochrome-c
      oxidase subunit 1 (Cox1), a 4 aa insert in CTP synthetase and a 5 aa insert in
      glutamyl-tRNA synthetase (GluRS). Additionally, the actinobacterial specificity
      of the large insert in the 23S rRNA was also tested. Using primers designed for
      conserved regions flanking these signatures, fragments of most of these genes
      were amplified from 23 actinobacterial species, covering many different families
      and orders, for which no sequence information was previously available. All the
      61 sequenced fragments, except two in GluRS, were found to contain the indicated
      signatures. The presence of these signatures in various species from 20 families
      within this phylum provides evidence that they are likely distinctive
      characteristics of the entire phylum, which were introduced in a common ancestor
      of this group. The absence of all four of these signatures in Symbiobacterium
      thermophilum suggests that this species, which is distantly related to other
      actinobacteria in 16S rRNA and CTP synthetase trees, may not be a part of the
      phylum Actinobacteria. The identified signatures provide novel molecular means
      for defining and circumscribing the phylum Actinobacteria. Functional studies on
      them should prove helpful in understanding novel biochemical and physiological
      characteristics of this group of bacteria.

PMID- 16280505
TI  - Halobacillus yeomjeoni sp. nov., isolated from a marine solar saltern in Korea.
AB  - A Gram-positive or Gram-variable, motile, endospore-forming, halophilic bacterial
      strain, MSS-402T, was isolated from a marine solar saltern in Korea, and
      subjected to a polyphasic taxonomic study. Some cells of strain MSS-402T were
      long filamentous rods. The isolate grew optimally at 37 degrees C and in the
      presence of 3-5 % (w/v) NaCl. Strain MSS-402T had cell-wall peptidoglycan based
      on l-orn-d-Asp, MK-7 as the predominant menaquinone and anteiso-C(15 : 0),
      anteiso-C(17 : 0) and iso-C(16 : 0) as major fatty acids. The DNA G+C content was
      42.9 mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that
      strain MSS-402T falls within the evolutionary radiation of species of the genus
      Halobacillus. Levels of 16S rRNA gene sequence similarity between strain MSS-402T
      and the type strains of recognized Halobacillus species ranged from 98.0 % (with
      Halobacillus halophilus) to 99.2 % (with Halobacillus litoralis and Halobacillus
      trueperi). Levels of DNA-DNA binding indicated that strain MSS-402T represents a
      genomic species that is distinct from recognized Halobacillus species. Strain MSS
      402T was differentiated from Halobacillus species by means of several phenotypic
      characteristics. On the basis of its phenotypic properties and phylogenetic and
      genetic distinctiveness, strain MSS-402T (=KCTC 3957T=DSM 17110T) should be
      classified as the type strain of a novel Halobacillus species, for which the name
      Halobacillus yeomjeoni sp. nov. is proposed.

PMID- 16280506
TI  - Reclassification of Alcaligenes latus strains IAM 12599T and IAM 12664 and
      Pseudomonas saccharophila as Azohydromonas lata gen. nov., comb. nov.,
      Azohydromonas australica sp. nov. and Pelomonas saccharophila gen. nov., comb.
      nov., respectively.
AB  - The aim of this study was to clarify the taxonomic position of the nitrogen
      fixing and hydrogen-oxidizing bacteria Alcaligenes latus strains IAM 12599T, IAM
      12664 and IAM 12665 and Pseudomonas saccharophila IAM 14368T. It was found that
      the type strain of Alcaligenes latus, IAM 12599T, showed 99 x 9 and 96 x 1 % 16S
      rRNA gene sequence similarity to strains IAM 12665 and IAM 12664, respectively. A
      comparison using DNA-DNA hybridization suggested that strains IAM 12599T and IAM
      12665 belong to a single species (89 x 7 %) and that strain IAM 12664 (35 x 1 %)
      forms a separate species. The phenotypic characteristics also support the
      conclusion that these bacteria should be identified as two species of a new
      genus: Azohydromonas lata gen. nov., comb. nov. (type strain IAM 12599T=DSM
      1122T=LMG 3321T=ATCC 29712T; reference strain IAM 12665=DSM 1123=LMG 3325=ATCC
      29714) and Azohydromonas australica sp. nov. (type strain IAM 12664T=DSM
      1124T=LMG 3324T=ATCC 29713T). Pseudomonas saccharophila IAM 14368T was found to
      be closely related to the phototrophic bacterium Roseateles depolymerans, with 96
      x 8 % 16S rRNA gene sequence similarity, but the two bacteria are quite different
      with respect to their metabolism and some significant phenotypic characteristics,
      suggesting that they cannot be included in a single genus. Further studies on
      their nifH gene sequences, G+C content of the DNA and cellular fatty acid
      composition confirm that Pseudomonas saccharophila should be reclassified: the
      name Pelomonas saccharophila gen. nov., comb. nov. is proposed, with the type
      strain IAM 14368T (=LMG 2256T=ATCC 15946T).

PMID- 16280507
TI  - Halolactibacillus halophilus gen. nov., sp. nov. and Halolactibacillus miurensis
      sp. nov., halophilic and alkaliphilic marine lactic acid bacteria constituting a
      phylogenetic lineage in Bacillus rRNA group 1.
AB  - Eleven novel strains of marine-inhabiting lactic acid bacteria that were isolated
      from living and decaying marine organisms collected from a temperate area of
      Japan are described. The isolates were motile with peritrichous flagella and non
      sporulating. They lacked catalase, quinones and cytochromes. Fermentation
      products from glucose were lactate, formate, acetate and ethanol. Lactate yield
      as percentage conversion from glucose was affected by the pH of the fermentation
      medium: approximately 55 % at the optimal growth pH of 8.0, greater than
      approximately 70 % at pH 7.0 and less than approximately 30 % at pH 9.0. The
      molar ratio of the other three products was the same at each cultivation pH,
      approximately 2 : 1 : 1. Carbohydrates and related compounds were aerobically
      metabolized to acetate and pyruvate as well as lactate. The isolates were
      slightly halophilic, highly halotolerant and alkaliphilic. The optimum NaCl
      concentration for growth was 2.0-3.0 % (w/v), with a range of 0-25.5 %. The
      optimum pH for growth was 8.0-9.5, with a range of 6.0-10.0. The G+C content of
      the DNA was 38.5-40.7 mol%. The isolates constituted two genomic species (DNA-DNA
      relatedness of less than 41 %) each characterized by sugar fermentation profiles.
      The cell-wall peptidoglycan of both phenotypes contained meso-diaminopimelic
      acid. The major cellular fatty acids were C(16 : 0) and a-C(13 : 0). Comparative
      sequence analysis of the 16S rRNA genes revealed that these isolates represent
      novel species constituting a phylogenetic unit outside the radiation of typical
      lactic acid bacteria and an independent line of descent within the group composed
      of the halophilic/halotolerant/alkaliphilic and/or alkalitolerant species in
      Bacillus rRNA group 1, with 94.8-95.1 % similarity to the genus Paraliobacillus,
      93.7-94.1 % to the genus Gracilibacillus and 93.8-94.2 % to Virgibacillus
      marismortui. On the basis of possession of physiological and biochemical
      characteristics common to typical lactic acid bacteria within Bacillus rRNA group
      1, chemotaxonomic characteristics and phylogenetic independence, a new genus and
      two species, Halolactibacillus halophilus gen. nov., sp. nov. and
      Halolatibacillus miurensis sp. nov., are proposed. The type strains are
      Halolactibacillus halophilus M2-2T (=DSM 17073T=IAM 15242T=NBRC 100868T=NRIC
      0628T) (G+C content 40.2 mol%) and Halolactibacillus miurensis M23-1T (=DSM
      17074T=IAM 15247T=NBRC 100873T=NRIC 0633T) (G+C content 38.5 mol%).

PMID- 16280508
TI  - Deinococcus deserti sp. nov., a gamma-radiation-tolerant bacterium isolated from
      the Sahara Desert.
AB  - Two gamma- and UV-radiation-tolerant, Gram-negative, rod-shaped bacterial
      strains, VCD115T and VCD117, were isolated from a mixture of sand samples
      collected in the Sahara Desert in Morocco and Tunisia, after exposure of the sand
      to 15 kGy gamma radiation. Phylogenetic analysis based on 16S rRNA gene sequences
      and DNA-DNA hybridizations showed that VCD115T and VCD117 are members of a novel
      species belonging to the genus Deinococcus, with Deinococcus grandis as its
      closest relative. The DNA G+C contents of VCD115T and VCD117 are 59.8 and 60.6
      mol%, respectively. The major fatty acids (straight-chain 15 : 1, 16 : 1, 17 : 1
      and 16 : 0), polar lipids (dominated by phosphoglycolipids and glycolipids) and
      quinone type (MK-8) support the affiliation to the genus Deinococcus. The strains
      did not grow on rich medium such as trypticase soy broth (TSB), but did grow as
      whitish colonies on tenfold-diluted TSB. The genotypic and phenotypic properties
      allowed differentiation of VCD115T and VCD117 from recognized Deinococcus
      species. Strains VCD115T and VCD117 are therefore identified as representing a
      novel species, for which the name Deinococcus deserti sp. nov. is proposed, with
      the type strain VCD115T (=DSM 17065T=LMG 22923T).

PMID- 16280509
TI  - Spiroplasma leucomae sp. nov., isolated in Poland from white satin moth (Leucoma
      salicis L.) larvae.
AB  - Spiroplasma sp. strain SMA(T), isolated in Poland from white satin moth larvae,
      Leucoma salicis L. (Lepidoptera: Lymantriidae), was serologically distinct from
      other Spiroplasma species, groups or subgroups. Dark-field microscopy of the
      cells revealed the classical helical shape and subsequent transmission electron
      microscopy revealed cells surrounded by only a single cell membrane (lacking a
      cell wall). Growth of strain SMA(T) occurred in M1D medium at 30 degrees C.
      Strain SMA(T) catabolized both glucose and arginine, but did not hydrolyse urea.
      The G+C content of the DNA was 24+/-1 mol% as determined by melting temperature
      analysis. Serological analysis revealed a very weak cross-reactivity (positive
      reaction only up to a 1 : 80 dilution) with two Spiroplasma strains, 277F
      (Spiroplasma sp. group I-4) and LB-12 (Spiroplasma sp. group I-5). Strain SMA(T)
      (=ATCC BAA-521T=NBRC 100392T) is designated the type strain of a novel species,
      Spiroplasma leucomae sp. nov. (class Mollicutes: order Entomoplasmatales: family
      Spiroplasmataceae).

PMID- 16280510
TI  - 'Candidatus Phytoplasma graminis' and 'Candidatus Phytoplasma caricae', two novel
      phytoplasmas associated with diseases of sugarcane, weeds and papaya in Cuba.
AB  - During 2003, surveys of sugarcane yellow leaf disease and papaya bunchy top-like
      disease were carried out on plantations in Havana province, Cuba, to determine
      the roles of weeds and Auchenorrhyncha insects in the epidemiology of these
      diseases. More than 250 plant and insect samples were collected and indexed by
      using a nested PCR for phytoplasma 16S rDNA with the generic primer pairs P1/P7
      and R16F2n/R16R2. The PCR products were further characterized by restriction
      fragment length polymorphism using HaeIII, AluI, Sau3AI, Tru9I, HhaI, HpaII and
      TaqI endonucleases, giving patterns that distinguished them from those of the
      other reference phytoplasmas analysed. Phylogenetic analysis of 16S rRNA gene
      sequences identified the phytoplasmas present in sugarcane (Saccharum officinarum
      L.), Cynodon dactylon L., Conyza canadensis L. Cronq., Sorghum halepense L.
      Pers., Macroptilium lathyroides L. Urb., Saccharosydne saccharivora (Westwood)
      and Cedusa spp., and those in papaya (Carica papaya L.) and Empoasca papayae, as
      two novel provisional phytoplasma species. We propose that these phytoplasmas
      should be given Candidatus status, as 'Candidatus Phytoplasma graminis' and
      'Candidatus Phytoplasma caricae', respectively.

PMID- 16280511
TI  - Methanomethylovorans thermophila sp. nov., a thermophilic, methylotrophic
      methanogen from an anaerobic reactor fed with methanol.
AB  - A novel thermophilic, obligately methylotrophic, methanogenic archaeon, strain
      L2FAW(T), was isolated from a thermophilic laboratory-scale upflow anaerobic
      sludge blanket reactor fed with methanol as the carbon and energy source. Cells
      of strain L2FAW(T) were non-motile, irregular cocci, 0.7-1.5 mum in diameter and
      usually occurred singly (sometimes forming clusters of two or four cells). The
      cells stained Gram-negative and lysed immediately in 0.1 % (w/v) SDS. Growth was
      inhibited by chloramphenicol and tetracycline, but not by penicillin, bacitracin,
      spectinomycin, vancomycin or kanamycin. Methanol and mono-, di- and
      trimethylamine were used as substrates, but H2/CO2, formate, acetate, propanol,
      dimethyl sulfide and methanethiol were not. The temperature range for growth was
      42-58 degrees C, with an optimum at 50 degrees C. The fastest growth was observed
      at a salinity below 100 mM NaCl; no growth occurred above 300 mM NaCl. The
      optimal pH for growth was 6.5; growth was observed from pH 5 to pH 7.5. The G+C
      content of the genomic DNA was 37.6 mol%. Analysis of the 16S rRNA gene sequence
      and the partial methyl-CoM reductase gene sequence revealed that the organism was
      phylogenetically closely related to Methanomethylovorans hollandica DMS1T (98 %
      similarity for the 16S rRNA gene sequence and 91 % similarity for the methyl-CoM
      reductase gene sequence). The DNA-DNA relatedness between L2FAW(T) and
      Methanomethylovorans hollandica DMS1T was 46 %. On the basis of these results,
      strain L2FAW(T) (=DSM 17232T=ATCC BAA-1173T) represents the type strain of a
      novel species, for which the name Methanomethylovorans thermophila sp. nov. is
      proposed.

PMID- 16280512
TI  - Dialister micraerophilus sp. nov. and Dialister propionicifaciens sp. nov.,
      isolated from human clinical samples.
AB  - Seventeen anaerobic, Gram-negative, tiny coccobacilli were collected in France
      from various human clinical samples. Biochemical analyses as well as molecular
      studies, including 16S rRNA and dnaK gene sequencing, affiliated all the isolates
      to the genus Dialister. However, 16S rRNA and dnaK gene sequence similarities
      were below 95.2 and 79.7 %, respectively, when comparisons were performed with
      the currently described species Dialister pneumosintes and Dialister invisus. Two
      clusters consisting of 13 and four isolates could be differentiated. 16S rRNA-
      and dnaK-based phylogeny confirmed that these two clusters represent two novel
      and distinct lineages within the genus Dialister. Finally, phenotypic, genotypic
      and phylogenetic data supported the proposal of the two novel species Dialister
      micraerophilus sp. nov. (type strain ADV 04.01T=AIP 25.04T=CIP 108278T=CCUG
      48837T) and Dialister propionicifaciens sp. nov. (type strain ADV 1053.03T=AIP
      26.04T=CIP 108336T=CCUG 49291T). The G+C content of the DNA of the D.
      micraerophilus type strain is 36.3 mol%. On the basis of 16S rRNA gene sequence
      analysis, 11 isolates originating from Canada could also be affiliated to D.
      micraerophilus sp. nov., and were included in the species description.

PMID- 16280513
TI  - Enterococcus devriesei sp. nov., associated with animal sources.
AB  - The taxonomic position of two bovine strains, LMG 13603 and LMG 14595, assigned
      to the species Enterococcus raffinosus on the basis of biochemical features, was
      reinvestigated. Both reference strains and two other isolates, 6/1 (=LMG 22829)
      originating from a charcoal-broiled river lamprey and IE38.4 (=LMG 22830) from
      the air of a poultry slaughter by-product processing plant, occupied a clearly
      separate position, on the basis of sequence analysis of the housekeeping gene
      pheS (encoding the phenylalanyl-tRNA synthase alpha-subunit), relative to the
      type strain of E. raffinosus and all other enterococcal species with validly
      published names. 16S rRNA gene sequencing of strains LMG 13603, LMG 14595, 6/1
      and IE38.4 confirmed their phylogenetic position in the Enterococcus avium
      species group, there being more than 99 % 16S rRNA gene sequence similarity to
      most members of the group, including E. raffinosus, and revealed Enterococcus
      pseudoavium as the closest phylogenetic relative (99.8-99.9 %). Further
      phenotypic and genotypic analyses using whole-cell-protein electrophoresis,
      (GTG)(5)-PCR fingerprinting, ribotyping and DNA-DNA hybridization experiments
      demonstrated that all four strains represent a novel enterococcal species, for
      which the name Enterococcus devriesei sp. nov. is proposed. The type strain is
      LMG 14595T (=CCM 7299T).

PMID- 16280514
TI  - Lactobacillus arizonensis is a later heterotypic synonym of Lactobacillus
      plantarum.
AB  - The 'Lactobacillus plantarum group' encompasses the taxa Lactobacillus plantarum
      subsp. plantarum, Lactobacillus plantarum subsp. argentoratensis, Lactobacillus
      paraplantarum, Lactobacillus pentosus and Lactobacillus arizonensis. In this
      study, the phylogenetic position of L. arizonensis was examined using 16S rRNA
      gene-specific methodologies (16S rRNA sequencing and ribotyping) and genomic DNA
      based investigations [repetitive extragenic palindromic DNA (rep)-PCR and DNA-DNA
      hybridization]. Our results show that the L. arizonensis type strain could not be
      distinguished from the type strain of L. plantarum or from various L. plantarum
      reference strains. Therefore, it is proposed that the species L. arizonensis
      should be reclassified as a heterotypic synonym of L. plantarum.

PMID- 16280515
TI  - Terrabacter terrae sp. nov., a novel actinomycete isolated from soil in Spain.
AB  - A Gram-positive, aerobic, long-rod-shaped, non-spore-forming bacterium (strain
      PPLB(T)) was isolated from soil mixed with Iberian pig hair. This actinomycete
      showed keratinase activity in vitro when chicken feathers were added to the
      culture medium. Strain PPLB(T) was oxidase-negative and catalase-positive and
      produced lipase and esterase lipase. This actinomycete grew at 40 degrees C on
      nutrient agar and in the same medium containing 5 % (w/v) NaCl. Growth was
      observed with many different carbohydrates as the sole carbon source. On the
      basis of 16S rRNA gene sequence similarity, strain PPLB(T) was shown to belong to
      the genus Terrabacter of the family Intrasporangiaceae. Strain PPLB(T) showed
      98.8 % 16S rRNA gene sequence similarity to Terrabacter tumescens. Chemotaxonomic
      data, such as the main ubiquinone (MK-8), the main polar lipids
      (phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylinositol) and
      the main fatty acids (i-C(15 : 0), ai-C(15 : 0), i-C(16 : 0) and ai-C(17 : 0))
      supported the affiliation of strain PPLB(T) to the genus Terrabacter. The G+C
      content of the DNA was 71 mol%. The results of DNA-DNA hybridization (36.6 %
      relatedness between Terrabacter tumescens and strain PPLB(T)) and physiological
      and biochemical tests suggested that strain PPLB(T) belongs to a novel species of
      the genus Terrabacter, for which the name Terrabacter terrae sp. nov. is
      proposed. The type strain is PPLB(T) (=CECT 3379T=LMG 22921T).

PMID- 16280516
TI  - Gramella portivictoriae sp. nov., a novel member of the family Flavobacteriaceae
      isolated from marine sediment.
AB  - A yellow-pigmented, Gram-negative, slowly gliding, rod-shaped, strictly aerobic
      bacterium (UST040801-001T) was isolated from marine sediment. The DNA G+C content
      was 39.9 mol%. The predominant fatty acids were a15 : 0, i15 : 0, i15 : 0 3-OH,
      i17 : 1omega9c, i17 : 0 3-OH and summed feature 3, comprising i15 : 0 2-OH and/or
      16 : 1omega7c (altogether representing 76.2 % of the total). MK-6 was the only
      respiratory quinone. Flexirubin-type pigments were not produced. Phylogenetic
      analysis based on 16S rRNA gene sequences indicated that Gramella echinicola KMM
      6050T (the only species in the genus) was the closest relative of UST040801-001T,
      sharing 98.0 % sequence similarity. The DNA-DNA relatedness between UST040801
      001T and Gramella echinicola KMM 6050T was 13 %. Strain UST040801-001T can be
      distinguished from G. echinicola by means of 11 phenotypic traits. The results of
      molecular and phenotypic analyses suggested that UST040801-001T represents a
      novel species of Gramella. The name Gramella portivictoriae sp. nov. is proposed
      for this bacterium, with UST040801-001T (=NRRL B-41137T [corrected] =JCM 13192T)
      as the type strain.

PMID- 16280517
TI  - Halalkalicoccus tibetensis gen. nov., sp. nov., representing a novel genus of
      haloalkaliphilic archaea.
AB  - A haloalkaliphilic archaeon (strain DS12T) isolated from Lake Zabuye, the Tibetan
      Plateau, China, was characterized to elucidate its taxonomy. The strain was
      aerobic, chemo-organotrophic, and grew optimally at 40 degrees C, pH 9.5-10.0 and
      3.4 M NaCl. Cells of strain DS12T were non-motile cocci and stained Gram
      variable. The major polar lipids of strain DS12T were diphytanyl and phytanyl
      sesterterpanyl diether derivatives of phosphatidylglycerol and
      phosphatidylglycerol phosphate methyl ester. No glycolipids were detected.
      Phylogenetic analysis revealed that the strain formed a distinct lineage within
      the family Halobacteriaceae. The low 16S rRNA gene sequence similarity values to
      its closest relatives (91.5-92.5 %) and its signature bases both suggest that the
      strain has no close affinity with any members of the family Halobacteriaceae with
      validly published names. Therefore, it is proposed that strain DS12T (=AS
      1.3240T=JCM 11890T) represents the type strain of a novel species in a new genus,
      Halalkalicoccus tibetensis gen. nov., sp. nov.

PMID- 16280518
TI  - Thermococcus coalescens sp. nov., a cell-fusing hyperthermophilic archaeon from
      Suiyo Seamount.
AB  - A cell-fusing hyperthermophilic archaeon was isolated from hydrothermal fluid
      obtained from Suiyo Seamount of the Izu-Bonin Arc. The isolate, TS1(T), is an
      irregular coccus, usually 0.5-2 microm in diameter and motile with a polar tuft
      of flagella. Cells in the exponential phase of growth fused at room temperature
      in the presence of DNA-intercalating dye to become as large as 5 microm in
      diameter. Fused cells showed dark spots that moved along in the cytoplasm. Large
      cells with a similar appearance were also observed upon culture at 87 degrees C,
      suggesting the occurrence of similar cell fusions during growth. Transmission
      electron microscopy revealed that cells in the exponential phase possessed a thin
      and electron-lucent cell envelope that could be lost subsequently during culture.
      The fragile cell envelope must be related to cell fusion. The cells grew at 57-90
      degrees C, pH 5.2-8.7 and at NaCl concentrations of 1.5-4.5 %, with the optima
      being 87 degrees C, pH 6.5 and 2.5 % NaCl. The isolate was an anaerobic chemo
      organotroph that grew on either yeast extract or tryptone as the sole growth
      substrate. The genomic DNA G+C content was 53.9 mol%. Phylogenetic analysis based
      on 16S rRNA gene sequencing indicated that the isolate was closely related to
      Thermococcus species. However, no significant DNA-DNA hybridization was observed
      between genomic DNA of strain TS1(T) and phylogenetically related Thermococcus
      species. We propose that isolate TS1(T) represents a novel species, Thermococcus
      coalescens sp. nov., with the name reflecting the cell fusion activity observed
      in the strain. The type strain is TS1(T) (=JCM 12540T=DSM 16538T).

PMID- 16280519
TI  - Bacteroides coprosuis sp. nov., isolated from swine-manure storage pits.
AB  - Two Gram-negative, anaerobic, non-spore-forming, rod-shaped organisms were
      isolated from a swine-manure storage pit. Based on morphological and biochemical
      criteria, the strains were tentatively identified as belonging to the genus
      Bacteroides but they did not appear to correspond to any recognized species of
      the genus. Comparative 16S rRNA gene sequencing studies showed that the strains
      were related closely to each other and confirmed their placement in the genus
      Bacteroides, but sequence divergence values of >10 % from reference Bacteroides
      species demonstrated that the organisms from manure represent a novel species.
      Based on biochemical criteria and molecular genetic evidence, it is proposed that
      the unknown isolates from manure be assigned to a novel species of the genus
      Bacteroides, as Bacteroides coprosuis sp. nov. The type strain is PC139T (=CCUG
      50528T=NRRL B-41113T).

PMID- 16280520
TI  - Pseudoalteromonas byunsanensis sp. nov., isolated from tidal flat sediment in
      Korea.
AB  - A Gram-negative, motile, strictly aerobic, violet-pigment-producing bacterium,
      designated strain FR1199T, was isolated from tidal flat sediment of Byunsan,
      South Korea. Phylogenetic analysis of the 16S rRNA gene sequence revealed that
      strain FR1199T represents a distinct line of descent within the genus
      Pseudoalteromonas. The phenotypic features of strain FR1199T were similar to
      those of Pseudoalteromonas phenolica and Pseudoalteromonas luteoviolacea, but
      several physiological and chemotaxonomical properties readily distinguished
      strain FR1199T from these species. Major fatty acids were straight-chain
      saturated (C(16 : 0)) and monounsaturated C(18 : 1)omega7c fatty acids. The DNA
      G+C content was 39 mol%. On the basis of polyphasic evidence, it is concluded
      that the isolate represents a novel species within the genus Pseudoalteromonas,
      for which the name Pseudoalteromonas byunsanensis sp. nov. is proposed. The type
      strain is FR1199T (=JCM 12483T=KCTC 12274T).

PMID- 16280521
TI  - Palleronia marisminoris gen. nov., sp. nov., a moderately halophilic,
      exopolysaccharide-producing bacterium belonging to the 'Alphaproteobacteria',
      isolated from a saline soil.
AB  - Strain B33(T) is a moderately halophilic, exopolysaccharide-producing, Gram
      negative, non-motile rod isolated from a hypersaline soil bordering a saline
      saltern on the Mediterranean seaboard in Murcia (Spain). The bacterium is
      chemoheterotrophic and strictly aerobic. It contains a pink pigment but does not
      synthesize bacteriochlorophyll a. It requires 0.66 M Na+, 0.1 M Mg2+ and 0.1 M K+
      for optimum growth. It does not produce acid from carbohydrates. It cannot grow
      with carbohydrates, organic acids, sugars, alcohols or amino acids as sole
      sources of carbon and energy. Its major fatty-acids are 18 : 1omega7c (68.9 %)
      and 19 : 0 cyclo omega8c (12.8 %). The sole respiratory lipoquinone found in
      strain B33T is ubiquinone-10. The DNA G+C content is 64.2 mol%. 16S rRNA gene
      sequence comparisons show that the isolate is a member of the Roseobacter clade
      within the class 'Alphaproteobacteria'. The similarity values with Roseivivax
      halodurans and Roseivivax halotolerans are 88.2 and 88.0 % respectively and 92.2
      % with Salipiger mucosus. DNA-DNA hybridization values with these species are <30
      %. In the light of the polyphasic evidence gathered in this study it is proposed
      that the isolate be classified as a novel genus and species with the name
      Palleronia marisminoris gen. nov., sp. nov. The proposed type strain is strain
      B33T (=CECT 7066T=LMG 22959T).

PMID- 16280522
TI  - Isolation and characterization of methylotrophic methanogens from anoxic marine
      sediments in Skan Bay, Alaska: description of Methanococcoides alaskense sp.
      nov., and emended description of Methanosarcina baltica.
AB  - Three novel strains of methylotrophic methanogens were isolated from Skan Bay,
      Alaska, by using anaerobic cultivation techniques. The water was 65 m deep at the
      sampling site. Strains AK-4 (=OCM 774), AK-5T (=OCM 775T=DSM 17273T) and AK-9
      (=OCM 793) were isolated from the sulfate-reducing zone of the sediments. Each of
      the strains was a non-motile coccus and occurred singly. Cells grew with
      trimethylamine as a catabolic substrate and strain AK-4 could also catabolize
      methanol. Yeast extract and trypticase peptones were not required for growth, but
      their addition to the culture medium slightly stimulated growth. Each of the
      strains grew at temperatures of 5-28 degrees C; they were slight halophiles and
      grew fastest in the neutral pH range. Analysis of the 16S rRNA gene sequences
      indicated that strain AK-4 was most closely related to Methanosarcina baltica.
      DNA-DNA hybridization studies showed 88 % relatedness, suggesting that strain AK
      4 represents a novel strain within this species. Strains AK-5T and AK-9 had
      identical 16S rRNA gene sequences that were most closely related to the sequence
      of Methanococcoides burtonii (99.8 % sequence similarity). DNA-DNA hybridization
      studies showed that strains AK-5T and AK-9 are members of the same species (88 %
      relatedness value), but strain AK-5T had a DNA-DNA relatedness value of only 55 %
      to Methanococcoides burtonii. This indicates that strains AK-5T and AK-9 should
      be considered as members of a novel species in the genus Methanococcoides. We
      propose the name Methanococcoides alaskense sp. nov., with strain AK-5T (=OCM
      775T=DSM 17273T) as the type strain.

PMID- 16280523
TI  - Haloterrigena saccharevitans sp. nov., an extremely halophilic archaeon from Xin
      Jiang, China.
AB  - A novel extremely halophilic strain, isolated from Aibi salt lake, Xin-Jiang,
      China, was subjected to polyphasic taxonomic characterization. This strain,
      designated AB14T, is neutrophilic, motile and requires at least 10 % (w/v) NaCl
      for growth. Strain AB14T grows at 24-58 degrees C, with optimal growth at 42-45
      degrees C. Mg2+ is not required, but growth is observed in MgCl2 concentrations
      as high as 1.0 M. Strain AB14T possesses the diphytanyl (C20C20) and phytanyl
      sesterterpanyl diether (C20C25) derivatives of phosphatidylglycerol,
      phosphatidylglycerol phosphate methyl ester and mannose-2,6 disulfate 1-->2
      glucose-glycerol diether. The genomic DNA G+C content is 66.6 mol%. The 16S rRNA
      gene sequence similarity values of strain AB14T with its nearest phylogenetic
      neighbours (Haloterrigena thermotolerans and Haloterrigena turkmenica) are 98.6
      and 96.0 %, respectively. DNA-DNA hybridization revealed 54 % relatedness between
      strain AB14T and Haloterrigena thermotolerans JCM 11050T and 21 % between strain
      AB14T and Haloterrigena turkmenica JCM 9101T. It is therefore proposed that
      strain AB14T represents a novel species, for which the name Haloterrigena
      saccharevitans sp. nov. is proposed. The type strain is AB14T (=AS 1.3730T=JCM
      12889T).

PMID- 16280524
TI  - Rhizobium daejeonense sp. nov. isolated from a cyanide treatment bioreactor.
AB  - A polyphasic study was carried out to determine the taxonomic position of two
      aerobic, cyanide-degrading bacterial strains, designated L61T and L22, which had
      been isolated from a bioreactor for the treatment of nickel-complexed cyanide.
      The two isolates exhibited almost identical taxonomic characteristics.
      Phylogenetic analysis inferred from comparative 16S rRNA gene sequences indicated
      that the isolates fall in a sublineage of the genus Rhizobium comprising the type
      strains of Rhizobium giardinii, Rhizobium radiobacter, Rhizobium rubi, Rhizobium
      larrymoorei, Rhizobium vitis, Rhizobium undicola, Rhizobium loessense, Rhizobium
      galegae and Rhizobium huautlense. Cells of the two isolates are Gram-negative,
      aerobic, motile and non-spore-forming rods (0.6-0.7x1.1-1.3 microm), with
      peritrichous flagella. The DNA G+C content is 60.1-60.9 mol%. Cellular fatty
      acids are C(16 : 0) (2.2-3.3 %), C(18 : 0) (2.1-3.2 %), C(19 : 0) cyclo omega8c
      (9.9-16.8 %), C(20 : 3)omega6,9,12c (2.7-3.3 %), summed feature 3 (7.2-7.7 %) and
      summed feature 7 (67.8-73.7 %). The strains formed nodules on a legume plant,
      Medicago sativa. A nifH gene encoding denitrogenase reductase, the key component
      of the nitrogenase enzyme complex, was detected in L61T by PCR amplification by
      using a nifH-specific primer system. Strains L61T and L22 were distinguished from
      the type strains of recognized Rhizobium species in the same sublineage based on
      low DNA-DNA hybridization values (2-4 %) and/or a 16S rRNA gene sequence
      similarity value of less than 96 %. Moreover, some phenotypic properties with
      respect to substrate utilization as a carbon or nitrogen source, antibiotic
      resistance and growth conditions could be used to discriminate L61T and L22 from
      Rhizobium species in the same sublineage. Based on the results obtained in this
      study, L61T and L22 are considered to be representatives of a novel species of
      Rhizobium, for which the name Rhizobium daejeonense sp. nov. is proposed. The
      type strain is L61T (=KCTC 12121T=IAM 15042T=CCBAU 10050T).

PMID- 16280525
TI  - Bacillus ruris sp. nov., from dairy farms.
AB  - Four novel ellipsoidal spore-forming Bacillus isolates with swollen sporangia,
      isolated from raw milk and feed concentrate, showed a high level of similarity in
      SDS-PAGE, fatty acid methyl esters and routine phenotypic tests. However, 16S
      rRNA gene sequence comparisons showed that this taxon was different from other
      related Bacillus species, and only a low level of DNA relatedness was found with
      the closest phylogenetic and phenotypic relative, Bacillus galactosidilyticus.
      This taxon could be differentiated from B. galactosidilyticus on the basis of
      morphological differences, stronger acid reactions with a wide range of
      substrates after 48 h incubation, and qualitative and quantitative differences in
      fatty acid content. On the basis of these data, a novel species, Bacillus ruris
      sp. nov., is proposed, with LMG 22866T (=DSM 17057T) as the type strain.

PMID- 16280526
TI  - Oryzihumus leptocrescens gen. nov., sp. nov.
AB  - Three novel strains were isolated from a soil sample collected in Japan using GPM
      agar plates supplemented with superoxide dismutase and/or catalase. The strains
      were Gram-positive, catalase-positive, irregular rod-shaped bacteria with meso
      diaminopimelic acid as a peptidoglycan diagnostic diamino acid, and the acyl type
      of the peptidoglycan was acetyl. The major menaquinone was MK-8(H4). Mycolic
      acids were not detected. The G+C content of the DNA was 72-73 mol%. On the basis
      of morphological and chemotaxonomic properties and a phylogenetic analysis using
      16S rRNA gene sequences, these strains were classified as a novel genus and
      species, Oryzihumus leptocrescens gen. nov., sp. nov., in the family
      Intrasporangiaceae of the order Actinomycetales. The type strain is KV-628T
      (=NRRL B-24347T=JCM 12835T=NBRC 100762T).

PMID- 16280527
TI  - Actinoalloteichus spitiensis sp. nov., a novel actinobacterium isolated from a
      cold desert of the Indian Himalayas.
AB  - An actinobacterial strain, RMV-1378T, isolated from a cold desert of the Indian
      Himalayas, was subjected to polyphasic taxonomic characterization. The strain
      formed branching, non-fragmenting vegetative hyphae and did not produce
      diffusible pigments. Neither aerial mycelium nor spore formation was observed.
      The G+C content of the DNA was 72.0 mol%. The strain had chemotaxonomic
      characteristics typical of the genus Actinoalloteichus and was closely related
      (99.3 % 16S rRNA gene sequence similarity) to Actinoalloteichus cyanogriseus,
      currently the only Actinoalloteichus species with a validly published name.
      However, the results of DNA-DNA hybridization experiments showed 51.9 %
      relatedness with the type strain of A. cyanogriseus. On the basis of the above
      data and the physiological and biochemical distinctiveness of RMV-1378T (=MTCC
      6194T=JCM 12472T=DSM 44848T), this strain should be classified as the type strain
      of a novel species of Actinoalloteichus, for which the name Actinoalloteichus
      spitiensis sp. nov. is proposed.

PMID- 16280528
TI  - Description of two novel species, Sphingomonas abaci sp. nov. and Sphingomonas
      panni sp. nov.
AB  - Two Gram-negative, rod-shaped, non-spore-forming bacterial strains designated
      C42T and C52T were isolated in the Medical Clinic for Small Animals and Ungulates
      at the University for Veterinary Medicine Vienna, Austria. On the basis of 16S
      rRNA gene sequence similarity, both strains were shown to belong to the genus
      Sphingomonas. Strain C42T showed the greatest levels of sequence similarity with
      Sphingomonas melonis DSM 14444T and Sphingomonas aquatilis KCTC 2881T (both 97.7
      %). Strain C52T showed the greatest levels of sequence similarity with
      Sphingomonas koreensis KCTC 2882T (97.2 %), Sphingomonas aquatilis KCTC 2881T
      (97.1 %) and S. melonis DSM 14444T (97.0 %). The presence of Q-10 as the main
      ubiquinone, the predominance of the compound sym-homospermidine in the polyamine
      patterns, the presence of a Sphingomonadaceae-specific sphingoglycolipid in the
      polar lipid patterns, the presence of the fatty acid 2-OH C(14 : 0) and the lack
      of 3-hydroxy fatty acids supported the identification of the two novel strains as
      members of the genus Sphingomonas sensu stricto. Unique physiological
      characteristics, protein patterns, quantitative differences in their fatty acid
      profiles and the results of genomic fingerprinting and DNA-DNA hybridizations
      differentiated strains C42T and C52T from closely related Sphingomonas species.
      Hence, the two strains are described as novel species of the genus Sphingomonas
      sensu stricto. The names Sphingomonas abaci sp. nov. (type strain C42T=LMG
      21978T=DSM 15867T) and Sphingomonas panni sp. nov. (type strain C52T=LMG
      21979(T)=DSM 15761T) are proposed.

PMID- 16280529
TI  - Alcaligenes aquatilis sp. nov., a novel bacterium from sediments of the Weser
      Estuary, Germany, and a salt marsh on Shem Creek in Charleston Harbor, USA.
AB  - Four nitrite-dissimilating strains, isolated from Weser Estuary sediments, were
      investigated using a polyphasic taxonomic approach. Phylogenetic analysis based
      on 16S rRNA gene sequences indicated that these strains belong to the
      'Betaproteobacteria' and are related to the genus Alcaligenes. The highest level
      of sequence similarity (100 %) was found with strain M3A (=ATCC 700596), a
      dimethyl sulfide-producing marine isolate that was included in this study. DNA
      DNA hybridizations between the five strains and related Alcaligenes faecalis
      strains confirmed that the former belong to a single and novel species within the
      genus Alcaligenes. The isolates are Gram-negative, motile, rod-shaped cells with
      a DNA G+C content of about 56 mol%. The whole-cell fatty acid profiles of the
      isolates were very similar and included C(16 : 0), C(17 : 0) cyclo, C(18 :
      1)omega7c, summed feature 2 (comprising any combination of C(12 : 0) aldehyde, an
      unknown fatty acid of equivalent chain length 10.928, C(16 : 1) iso I and C(14 :
      0) 3-OH) and summed feature 3 (C(15 : 0) iso 2-OH and/or C(16 : 1)omega7c) as the
      major fatty acid components. On the basis of their phylogenetic, genomic and
      phenotypic properties, the five novel strains can be assigned to the genus
      Alcaligenes as a novel species, for which the name Alcaligenes aquatilis sp. nov.
      is proposed. The type strain is LMG 22996T (=CCUG 50924T).

PMID- 16280530
TI  - Paenibacillus assamensis sp. nov., a novel bacterium isolated from a warm spring
      in Assam, India.
AB  - A polyphasic approach was used to characterize a bacterium, GPTSA 11(T), isolated
      from a warm spring located in a reserve forest in Assam, India. The cells are
      Gram-variable, strictly aerobic, sporulating motile rods. The major fatty acids
      of the strain are C(15 : 0) anteiso (48.42 %), C(16 : 0) iso (11.59 %), C(16 :
      1)omega11c (6.16 %), C(15 : 0) iso (6.03 %), C(17 : 0) anteiso (5.68 %) and C(16
      : 1)omega7c alcohol (5.01 %). The presence of the fatty acid C(16 : 1)omega7c
      alcohol distinguishes this strain from other closely related species of the genus
      Paenibacillus. The strain contains MK-7 as the diagnostic menaquinone. The G+C
      content of the genomic DNA is 41.2 mol%. Analysis of the 16S rRNA gene sequence
      (1466 nt) revealed the presence of signature sequences PAEN 515F (5'
      GAGTAACTGCTCTCGGAATGACGGTACTTGAGAAGAAAGCCCC-3') and PAEN 862F (5'
      TCGATACCCTTGGTGCCGAAGT-3'), which were found in the species of the genus
      Paenibacillus surveyed by Shida et al. [Shida, O., Takagi, H., Kadowaki, K.,
      Nakamura, L. K. & Komagata, K. (1997). Int J Syst Bacteriol 47, 289-298]. The
      sequence shows closest similarity (95.85 %) to that of Paenibacillus apiarius,
      followed by Paenibacillus alvei (94.34 %), Paenibacillus cineris (93.87 %),
      Paenibacillus favisporus (93.80 %), Paenibacillus chibensis (93.47 %) and
      Paenibacillus azoreducens (93.40 %). Biochemical, physiological, chemotaxonomic
      and phylogenetic analyses justify placement of the strain in the genus
      Paenibacillus but not within any existing species. It should, therefore, be
      considered as representing a novel species, for which the name Paenibacillus
      assamensis sp. nov. is proposed. The type strain is GPTSA 11T (=MTCC 6934T=JCM
      13186T).

PMID- 16280531
TI  - Pontibacter actiniarum gen. nov., sp. nov., a novel member of the phylum
      'Bacteroidetes', and proposal of Reichenbachiella gen. nov. as a replacement for
      the illegitimate prokaryotic generic name Reichenbachia Nedashkovskaya et al.
      2003.
AB  - The taxonomic position of a marine, gliding, pink-pigmented, aerobic,
      heterotrophic and Gram-negative bacterium was established using a polyphasic
      approach. 16S rRNA gene sequence analysis indicated that the strain was a member
      of the phylum 'Bacteroidetes' in which it occupied a separate lineage. The
      predominant cellular fatty acids were C15 : 0 iso, C17 : 0 iso 3-OH, summed
      feature 3 and summed feature 4. The DNA G+C content was 48.7 mol%. Phylogenetic
      evidence and the results of phenotypic, genotypic and chemotaxonomic analyses
      strongly support the assignment of the newly isolated bacterium as a member of a
      novel genus and species, for which the name Pontibacter actiniarum gen. nov., sp.
      nov. is proposed. The type strain is KMM 6156T (=KCTC 12367T=LMG 23027T). It is
      also proposed that the illegitimate names Reichenbachia and Reichenbachia
      agariperforans are replaced with Reichenbachiella and Reichenbachiella
      agariperforans, respectively.

PMID- 16280533
TI  - Telonema antarcticum sp. nov., a common marine phagotrophic flagellate.
AB  - Telonema is a widely distributed group of phagotrophic flagellates with two known
      members. In this study, the structural identity and molecular phylogeny of
      Telonema antarcticum was investigated and a valid description is proposed.
      Molecular phylogeny was studied using small-subunit rRNA (SSU rRNA) gene
      sequences. The pear-shaped cell had two subequal flagella that emerged laterally
      on the truncated antapical tail. One flagellum had tripartite hairs. The cell was
      naked, but had subsurface vesicles containing angular paracrystalline bodies of
      an unknown nature. A unique complex cytoskeletal structure, the subcortical
      lamina, was found to be an important functional and taxonomic feature of the
      genus. Telonema has an antero-ventral depression where food particles are
      ingested and then transferred to a conspicuous anterior food vacuole. The
      molecular phylogeny inferred from the SSU rRNA gene sequence suggested that
      Telonema represents an isolated and deep branch among the tubulocristate
      protists.

PMID- 16280532
TI  - Mycoplasma amphoriforme sp. nov., isolated from a patient with chronic
      bronchopneumonia.
AB  - A mycoplasma was isolated from the sputum of an immunodeficient patient with
      recurrent bronchitis. The isolate designated strain A39T was very fastidious and
      atypical for a mycoplasma in its colonial appearance. Classical biochemical tests
      for mycoplasma speciation could not differentiate the isolate from the pathogens
      Mycoplasma pneumoniae and Mycoplasma genitalium and serological identification as
      a recognized Mycoplasma species was lacking. Specific PCR detection for these two
      species was negative. Subsequently, other strains were isolated from human
      patients that appeared to be similar to strain A39T in their physiological and
      genetic characteristics. Analysis of the 16S rRNA gene placed strain A39T and
      other isolates in the pneumoniae group of mycoplasmas, with the highest sequence
      similarity to Mycoplasma testudinis (96.8 %), but with only 93.0 % similarity to
      M. pneumoniae and M. genitalium. Examination of the 16S-23S rRNA internally
      transcribed spacer sequence, protein electrophoresis profile, genome size and
      serological reactions indicated that this organism represents a novel species,
      for which the name Mycoplasma amphoriforme sp. nov. is proposed, with strain A39T
      (=NCTC 11740T=ATCC BAA-992T) as the type strain.

PMID- 16280534
TI  - Culturing and environmental DNA sequencing uncover hidden kinetoplastid
      biodiversity and a major marine clade within ancestrally freshwater Neobodo
      designis.
AB  - Bodonid flagellates (class Kinetoplastea) are abundant, free-living protozoa in
      freshwater, soil and marine habitats, with undersampled global biodiversity. To
      investigate overall bodonid diversity, kinetoplastid-specific PCR primers were
      used to amplify and sequence 18S rRNA genes from DNA extracted from 16 diverse
      environmental samples; of 39 different kinetoplastid sequences, 35 belong to the
      subclass Metakinetoplastina, where most group with the genus Neobodo or the
      species Bodo saltans, whilst four group with the subclass Prokinetoplastina
      (Ichthyobodo). To study divergence between freshwater and marine members of the
      genus Neobodo, 26 new Neobodo designis strains were cultured and their 18S rRNA
      genes were sequenced. It is shown that the morphospecies N. designis is a
      remarkably ancient species complex with a major marine clade nested among older
      freshwater clades, suggesting that these lineages were constrained
      physiologically from moving between these environments for most of their long
      history. Other major bodonid clades show less-deep separation between marine and
      freshwater strains, but have extensive genetic diversity within all lineages and
      an apparently biogeographically distinct distribution of B. saltans subclades.
      Clade-specific 18S rRNA gene primers were used for two N. designis subclades to
      test their global distribution and genetic diversity. The non-overlap between
      environmental DNA sequences and those from cultures suggests that there are
      hundreds, possibly thousands, of different rRNA gene sequences of free-living
      bodonids globally.

PMID- 16280535
TI  - Cellular identity of an 18S rRNA gene sequence clade within the class
      Kinetoplastea: the novel genus Actuariola gen. nov. (Neobodonida) with
      description of the type species Actuariola framvarensis sp. nov.
AB  - Environmental molecular surveys of microbial diversity have uncovered a vast
      number of novel taxonomic units in the eukaryotic tree of life that are
      exclusively known by their small-subunit (SSU) rRNA gene signatures. In this
      study, we reveal the cellular and taxonomic identity of a novel eukaryote SSU
      rRNA gene sequence clade within the Kinetoplastea. Kinetoplastea are ubiquitously
      distributed flagellated protists of high ecological and medical importance. We
      isolated an organism from the oxic-anoxic interface of the anoxic Framvaren Fjord
      (Norway), which branches within an unidentified kinetoplastean sequence clade.
      Ultrastructural studies revealed a typical cellular organization that
      characterized the flagellated isolate as a member of the order Neobodonida
      Vickerman 2004, which contains five genera. The isolate differed in several
      distinctive characters from Dimastigella, Cruzella, Rhynchobodo and Rhynchomonas.
      The arrangement of the microtubular rod that supports the apical cytostome and
      the cytopharynx differed from the diagnosis of the fifth described genus (Neobodo
      Vickerman 2004) within the order Neobodonida. On the basis of both molecular and
      microscopical data, a novel genus within the order Neobodonida, Actuariola gen.
      nov., is proposed. Here, we characterize its type species, Actuariola
      framvarensis sp. nov., and provide an in situ tool to access the organism in
      nature and study its ecology.

PMID- 16280536
TI  - Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005. Improved
      consensus network techniques for genome-scale phylogeny.
AB  - Although recent studies indicate that estimating phylogenies from alignments of
      concatenated genes greatly reduces the stochastic error, the potential for
      systematic error still remains, heightening the need for reliable methods to
      analyze multigene data sets. Consensus methods provide an alternative, more
      inclusive, approach for analyzing collections of trees arising from multiple
      genes. We extend a previously described consensus network method for genome-scale
      phylogeny (Holland, B. R., K. T. Huber, V. Moulton, and P. J. Lockhart. 2004.
      Using consensus networks to visualize contradictory evidence for species
      phylogeny. Mol. Biol. Evol. 21:1459-1461) to incorporate additional information.
      This additional information could come from bootstrap analysis, Bayesian
      analysis, or various methods to find confidence sets of trees. The new methods
      can be extended to include edge weights representing genetic distance. We use
      three data sets to illustrate the approach: 61 genes from 14 angiosperm taxa and
      one gymnosperm, 106 genes from eight yeast taxa, and 46 members of a gene family
      from 15 vertebrate taxa.

PMID- 16280537
TI  - Strong and weak male mutation bias at different sites in the primate genomes:
      insights from the human-chimpanzee comparison.
AB  - Male mutation bias is a higher mutation rate in males than in females thought to
      result from the greater number of germ line cell divisions in males. If errors in
      DNA replication cause most mutations, then the magnitude of male mutation bias,
      measured as the male-to-female mutation rate ratio (alpha), should reflect the
      relative excess of male versus female germ line cell divisions. Evolutionary
      rates averaged among all sites in a sequence and compared between mammalian sex
      chromosomes were shown to be indeed higher in males than in females. However, it
      is presently unknown whether individual classes of substitutions exhibit such
      bias. To address this issue, we investigated male mutation bias separately at non
      CpG and CpG sites using human-chimpanzee whole-genome alignments. We observed
      strong male mutation bias at non-CpG sites: alpha in the X-autosome comparison
      was approximately 6-7, which was similar to the male-to-female ratio in the
      number of germ line cell divisions. In contrast, mutations at CpG sites exhibited
      weak male mutation bias: alpha in the X-autosome comparison was only
      approximately 2-3. This is consistent with the methylation-induced and
      replication-independent mechanism of CpG transitions, which constitute the
      majority of mutations at CpG sites. Interestingly, our study also indicated weak
      male mutation bias for transversions at CpG sites, implying a spontaneous
      mechanism largely not associated with replication. Male mutation bias was equally
      strong at CpG and non-CpG sites located within unmethylated "CpG islands,"
      suggesting the replication-dependent origin of these mutations. Thus, we found
      that the strength of male mutation bias is nonuniform in the primate genomes.
      Importantly, we discovered that male mutation bias depends on the proportion of
      CpG sites in the loci compared. This might explain the differences in the
      magnitude of primate male mutation bias observed among studies.

PMID- 16280538
TI  - Beyond pairwise distances: neighbor-joining with phylogenetic diversity
      estimates.
AB  - The "neighbor-joining algorithm" is a recursive procedure for reconstructing
      trees that is based on a transformation of pairwise distances between leaves. We
      present a generalization of the neighbor-joining transformation, which uses
      estimates of phylogenetic diversity rather than pairwise distances in the tree.
      This leads to an improved neighbor-joining algorithm whose total running time is
      still polynomial in the number of taxa. On simulated data, the method outperforms
      other distance-based methods. We have implemented neighbor-joining for subtree
      weights in a program called MJOIN which is freely available under the Gnu Public
      License at http://bio.math.berkeley.edu/mjoin/.

PMID- 16280539
TI  - Tracing hybrid incompatibilities to single amino acid substitutions.
AB  - Deleterious interactions among genes cause reductions in fitness of
      interpopulation hybrids (hybrid breakdown). Identifying genes involved in hybrid
      breakdown has proven difficult, and few studies have addressed the molecular
      basis of this widespread phenomenon. Because proper function of the mitochondrial
      electron transport system (ETS) requires a coadapted set of nuclear and
      mitochondrial gene products, ETS genes present an attractive system for studying
      the evolution of coadapted gene complexes within isolated populations and the
      loss of fitness in interpopulation hybrids. Here we show the effects of single
      amino acid substitutions in cytochrome c (CYC) on its functional interaction with
      another ETS protein, cytochrome c oxidase (COX) in the intertidal copepod
      Tigriopus californicus. The individual and pairwise consequences of three
      naturally occurring amino acid substitutions in CYC are examined by site-directed
      mutagenesis and found to differentially effect the rates of CYC oxidation by COX
      variants from different source populations. In one case, we show that
      interpopulation hybrid breakdown in COX activity can be attributed to a single
      naturally occurring amino acid substitution in CYC.

PMID- 16280540
TI  - The fate of mutations surfing on the wave of a range expansion.
AB  - Many species, including humans, have dramatically expanded their range in the
      past, and such range expansions had certainly an impact on their genetic
      diversity. For example, mutations arising in populations at the edge of a range
      expansion can sometimes surf on the wave of advance and thus reach a larger
      spatial distribution and a much higher frequency than would be expected in
      stationary populations. We study here this surfing phenomenon in more detail, by
      performing extensive computer simulations under a two-dimensional stepping-stone
      model. We find that the probability of survival of a new mutation depends to a
      large degree on its proximity to the edge of the wave. Demographic factors such
      as deme size, migration rate, and local growth rate also influence the fate of
      these new mutations. We also find that the final spatial and frequency
      distributions depend on the local deme size of a subdivided population. This
      latter result is discussed in the light of human expansions in Europe as it
      should allow one to distinguish between mutations having spread with Paleolithic
      or Neolithic expansions. By favoring the spread of new mutations, a consequence
      of the surfing phenomenon is to increase the rate of evolution of spatially
      expanding populations.

PMID- 16280541
TI  - Molecular evolution of the ankyrin gene family.
AB  - Ankyrins are membrane adaptor molecules that play important roles in coupling
      integral membrane proteins to the spectrin-based cytoskeleton network. Human
      mutations of ankyrin genes lead to severe genetic diseases such as fatal cardiac
      arrhythmias and hereditary spherocytosis. To elucidate the evolutionary history
      of ankyrins, we have identified novel ankyrin sequences in insect, fish, frog,
      chicken, dog, and chimpanzee genomes and explored the phylogenetic relationships
      of the ankyrin gene family. Our data demonstrate that duplication of ankyrin
      genes occurred at two different stages. The first duplication resulted from an
      independent evolution event specific in Arthropoda after its divergence from
      Chordata. Following the separation from Urochordata, expansion of ankyrins in
      vertebrates involved ancestral genome duplications. We did not find evidence of
      coordinated arrangements of gene families of ankyrin-associated membrane proteins
      on paralogous chromosomes. In addition, evolution of the 24 ANK-repeats
      strikingly correlated with the exon boundary sites of ankyrin genes, which might
      have occurred before its duplication in vertebrates. Such correlation is
      speculated to bring functional diversity and complexity. Moreover, based on the
      phylogenetic analysis of the ANK-repeat domain, we put forward a novel model for
      the putative primordial ankyrin that contains the fourth six-ANK-repeat subdomain
      and the spectrin-binding domain. These findings will provide guides for future
      studies concerning structure, function, evolutionary origins of ankyrins, and
      possibly other cytoskeletal proteins.

PMID- 16280542
TI  - Evolution and development of the chordates: collagen and pharyngeal cartilage.
AB  - Chordates evolved a unique body plan within deuterostomes and are considered to
      share five morphological characters, a muscular postanal tail, a notochord, a
      dorsal neural tube, an endostyle, and pharyngeal gill slits. The phylum Chordata
      typically includes three subphyla, Cephalochordata, Vertebrata, and Tunicata, the
      last showing a chordate body plan only as a larva. Hemichordates, in contrast,
      have pharyngeal gill slits, an endostyle, and a postanal tail but appear to lack
      a notochord and dorsal neural tube. Because hemichordates are the sister group of
      echinoderms, the morphological features shared with the chordates must have been
      present in the deuterostome ancestor. No extant echinoderms share any of the
      chordate features, so presumably they have lost these structures evolutionarily.
      We review the development of chordate characters in hemichordates and present new
      data characterizing the pharyngeal gill slits and their cartilaginous gill bars.
      We show that hemichordate gill bars contain collagen and proteoglycans but are
      acellular. Hemichordates and cephalochordates, or lancelets, show strong
      similarities in their gill bars, suggesting that an acellular cartilage may have
      preceded cellular cartilage in deuterostomes. Our evidence suggests that the
      deuterostome ancestor was a benthic worm with gill slits and acellular gill
      cartilages.

PMID- 16280543
TI  - Evolutionary conservation of expression profiles between human and mouse
      orthologous genes.
AB  - Mouse models are often used to study human genes because it is believed that the
      expression and function are similar for the majority of orthologous genes between
      the two species. However, recent comparisons of microarray data from thousands of
      orthologous human and mouse genes suggested rapid evolution of gene expression
      profiles under minimal or no selective constraint. These findings appear to
      contradict non-array-based observations from many individual genes and imply the
      uselessness of mouse models for studying human genes. Because absolute levels of
      gene expression are not comparable between species when the data are generated by
      species-specific microarrays, use of relative mRNA abundance among tissues (RA)
      is preferred to that of absolute expression signals. We thus reanalyze human and
      mouse genome-wide gene expression data generated by oligonucleotide microarrays.
      We show that the mean correlation coefficient among expression profiles detected
      by different probe sets of the same gene is only 0.38 for humans and 0.28 for
      mice, indicating that current measures of expression divergence are flawed
      because the large estimation error (discrepancy in expression signal detected by
      different probe sets of the same gene) is mistakenly included in the between
      species divergence. When this error is subtracted, 84% of human-mouse orthologous
      gene pairs show significantly lower expression divergence than that of random
      gene pairs. In contrast to a previous finding, but consistent with the common
      sense, expression profiles of orthologous tissues between species are more
      similar to each other than to those of nonorthologous tissues. Furthermore, the
      evolutionary rate of expression divergence and that of coding sequence divergence
      are found to be weakly, but significantly positively correlated, when RA and the
      Euclidean distance are used to measure expression-profile divergence. These
      results highlight the importance of proper consideration of various estimation
      errors in comparing the microarray data between species.

PMID- 16280544
TI  - No evidence for tissue-specific adaptation of synonymous codon usage in humans.
AB  - It has been proposed that the synonymous codon usage of human tissue-specific
      genes was under selective pressure to modulate the expression of proteins by
      codon-mediated translational control (Plotkin, J. B., H. Robins, and A. J.
      Levine. 2004. Tissue-specific codon usage and the expression of human genes.
      Proc. Natl. Acad. Sci. USA 101:12588-12591.) To test this model, we analyzed by
      internal correspondence analysis the codon usage of 2,126 human tissue-specific
      genes expressed in 18 different tissues. We confirm that synonymous codon usage
      differs significantly between the tissues. However, the effect is very weak: the
      variability of synonymous codon usage between tissues represents only 2.3% of the
      total codon usage variability. Moreover, this variability is directly linked to
      isochore-scale (>100 kb) variability of GC-content that affect both coding and
      introns or intergenic regions. This demonstrates that variations of synonymous
      codon usage between tissue-specific genes expressed in different tissues are due
      to regional variations of substitution patterns and not to translational
      selection.

PMID- 16280545
TI  - Inference and analysis of the relative stability of bacterial chromosomes.
AB  - The stability of genomes is highly variable, both in terms of gene content and
      gene order. Here I calibrate the loss of gene order conservation (GOC) through
      time by fitting a simple probabilistic model on pairwise comparisons involving
      126 bacterial genomes. The model computes the probability of separation of pairs
      of contiguous genes per unit of time and fits the data better than previous ones
      while allowing a mechanistic interpretation for the loss of GOC with time.
      Although the information on operons is not used in the model, I observe, as
      expected, that most highly conserved pairs of genes are indeed within operons.
      However, even the other pairs are much more conserved than expected given the
      observed experimental rearrangement rates. After 500 Myr, about 50% of the
      originally contiguous orthologues remain so in the average genome. Hence, the
      large majority of rearrangements must be deleterious and random genome
      rearrangements are unlikely to provide for positively selected structural
      changes. I then use the deviations from the model to define an intrinsic measure
      of genome stability that allowed the comparison of distantly related genomes and
      the inference of ancestral states. This shows that clades differ in genome
      stability, with cyanobacteria being the least stable and gamma-proteobacteria the
      most stable. Without correction for phylogeny, free-living bacteria are the least
      stable group of genomes, followed by pathogens, and then endomutualists. However,
      after correction for phylogenetic inertia (or the removal of cyanobacteria from
      the analysis), there is no significant association between genome stability and
      lifestyle or genome size. Hence, although this method has allowed uncovering some
      of mechanisms leading to rearrangements, we still ignore the forces that
      differentially shape selection upon genome stability in different species.

PMID- 16280546
TI  - Expression pattern shifts following duplication indicative of
      subfunctionalization and neofunctionalization in regulatory genes of Arabidopsis.
AB  - Gene duplication plays an important role in the evolution of diversity and novel
      function and is especially prevalent in the nuclear genomes of flowering plants.
      Duplicate genes may be maintained through subfunctionalization and
      neofunctionalization at the level of expression or coding sequence. In order to
      test the hypothesis that duplicated regulatory genes will be differentially
      expressed in a specific manner indicative of regulatory subfunctionalization
      and/or neofunctionalization, we examined expression pattern shifts in duplicated
      regulatory genes in Arabidopsis. A two-way analysis of variance was performed on
      expression data for 280 phylogenetically identified paralogous pairs. Expression
      data were extracted from global expression profiles for wild-type root, stem,
      leaf, developing inflorescence, nearly mature flower buds, and seedpod. Gene,
      organ, and gene by organ interaction (G x O) effects were examined. Results
      indicate that 85% of the paralogous pairs exhibited a significant G x O effect
      indicative of regulatory subfunctionalization and/or neofunctionalization. A
      significant G x O effect was associated with complementary expression patterns in
      45% of pairwise comparisons. No association was detected between a G x O effect
      and a relaxed evolutionary constraint as detected by the ratio of nonsynonymous
      to synonymous substitutions. Ancestral gene expression patterns inferred across a
      Type II MADS-box gene phylogeny suggest several cases of regulatory
      neofunctionalization and organ-specific nonfunctionalization. Complete linkage
      clustering of gene expression levels across organs suggests that regulatory
      modules for each organ are independent or ancestral genes had limited expression.
      We propose a new classification, regulatory hypofunctionalization, for an overall
      decrease in expression level in one member of a paralogous pair while still
      having a significant G x O effect. We conclude that expression divergence
      specifically indicative of subfunctionalization and/or neofunctionalization
      contributes to the maintenance of most if not all duplicated regulatory genes in
      Arabidopsis and hypothesize that this results in increasing expression diversity
      or specificity of regulatory genes after each round of duplication.

PMID- 16280547
TI  - The origins of eukaryotic gene structure.
AB  - Most of the phenotypic diversity that we perceive in the natural world is
      directly attributable to the peculiar structure of the eukaryotic gene, which
      harbors numerous embellishments relative to the situation in prokaryotes. The
      most profound changes include introns that must be spliced out of precursor
      mRNAs, transcribed but untranslated leader and trailer sequences (untranslated
      regions), modular regulatory elements that drive patterns of gene expression, and
      expansive intergenic regions that harbor additional diffuse control mechanisms.
      Explaining the origins of these features is difficult because they each impose an
      intrinsic disadvantage by increasing the genic mutation rate to defective
      alleles. To address these issues, a general hypothesis for the emergence of
      eukaryotic gene structure is provided here. Extensive information on absolute
      population sizes, recombination rates, and mutation rates strongly supports the
      view that eukaryotes have reduced genetic effective population sizes relative to
      prokaryotes, with especially extreme reductions being the rule in multicellular
      lineages. The resultant increase in the power of random genetic drift appears to
      be sufficient to overwhelm the weak mutational disadvantages associated with most
      novel aspects of the eukaryotic gene, supporting the idea that most such changes
      are simple outcomes of semi-neutral processes rather than direct products of
      natural selection. However, by establishing an essentially permanent change in
      the population-genetic environment permissive to the genome-wide repatterning of
      gene structure, the eukaryotic condition also promoted a reliable resource from
      which natural selection could secondarily build novel forms of organismal
      complexity. Under this hypothesis, arguments based on molecular, cellular, and/or
      physiological constraints are insufficient to explain the disparities in gene,
      genomic, and phenotypic complexity between prokaryotes and eukaryotes.

PMID- 16280548
TI  - Apicobasal polarity complexes.

PMID- 16280549
TI  - Caught Nek-ing: cilia and centrioles.
AB  - The Nek family of cell-cycle kinases is widely represented in eukaryotes and
      includes numerous proteins that were described only recently and remain poorly
      characterized. Comparing Neks in the context of clades allows us to examine the
      question of whether microbial eukaryotic Neks, although not strictly orthologs of
      their vertebrate counterparts, can provide clues to ancestral functions that
      might be retained in the vertebrate Neks. Relatives of the Nek2/NIMA proteins
      play important roles at the G2-M transition in nuclear envelope breakdown and
      centromere separation. Nek6, Nek7 and Nek9 also seem to regulate mitosis. By
      contrast, Nek1 and Nek8 have been linked with polycystic kidney disease. Results
      of statistical analysis indicate that the family coevolved with centrioles that
      function as both microtubule-organizing centers and the basal bodies of cilia.
      This evolutionary perspective, taken together with functional studies of
      microbial Neks, provides new insights into the cellular roles of the proteins and
      disease with which some of them have been linked.

PMID- 16280550
TI  - Secrets of a double agent: CDK7 in cell-cycle control and transcription.
AB  - In metazoans, cyclin-dependent kinase 7 (CDK7) has essential roles in both the
      cell-division cycle and transcription, as a CDK-activating kinase (CAK) and as a
      component of the general transcription factor TFIIH, respectively. Controversy
      over its double duty has been resolved, but questions remain. First, how does
      CDK7 achieve the dual substrate specificity necessary to perform both roles?
      Second, is there a deeper connection implied by the dichotomy of CDK7 function,
      for example similar mechanisms controlling cell division and gene expression,
      and/or actual coordination of the two processes? Enzymological studies have
      revealed solutions to the unusual substrate recognition problem, and there is
      evidence that the distinct functions of CDK7 can be regulated independently.
      Finally, despite divergence in their wiring, the CAK-CDK networks of budding
      yeast, fission yeast and metazoans all link transcriptional regulation with
      operation of the cell-cycle machinery. This connection might help to ensure that
      mRNAs encoding effectors of cell division are expressed at the right time in the
      cycle.

PMID- 16280551
TI  - A WAVE2-Abi1 complex mediates CSF-1-induced F-actin-rich membrane protrusions and
      migration in macrophages.
AB  - Colony-stimulating factor 1 (CSF-1) is an important physiological chemoattractant
      for macrophages. The mechanisms by which CSF-1 elicits the formation of
      filamentous actin (F-actin)-rich membrane protrusions and induces macrophage
      migration are not fully understood. In particular, very little is known regarding
      the contribution of the different members of the Wiskott-Aldrich Syndrome protein
      (WASP) family of actin regulators in response to CSF-1. Although a role for WASP
      itself in macrophage chemotaxis has been previously identified, no data was
      available regarding the function of WASP family verprolin-homologous (WAVE)
      proteins in this cell type. We found that WAVE2 was the predominant isoform to be
      expressed in primary macrophages and in cells derived from the murine
      monocyte/macrophage RAW264.7 cell line (RAW/LR5). CSF-1 treatment of macrophages
      resulted in WAVE2 accumulation in F-actin-rich protrusions induced by CSF-1.
      Inhibition of WAVE2 function by expressing a dominant-negative mutant or
      introducing anti-WAVE2 antibodies in RAW/LR5 cells, as well as reduction of
      endogenous WAVE2 expression by RNA-mediated interference (RNAi), resulted in a
      significant reduction of CSF-1-elicited F-actin protrusions. WAVE2 was found in a
      protein complex together with Abelson kinase interactor 1 (Abi1) in resting or
      stimulated cells. Both WAVE2 and Abi1 were recruited to and necessary for the
      formation of F-actin protrusions in response to CSF-1. Reducing the levels of
      WAVE2, directly or by targeting Abi1, resulted in an impaired cell migration to
      CSF-1. Altogether these data identify a WAVE2-Abi1 complex crucial for the normal
      actin cytoskeleton reorganization and migration of macrophages in response to CSF
      1.

PMID- 16280554
TI  - Hope in the darkest days: breastfeeding support in emergencies.

PMID- 16280553
TI  - Involvement of Rac in actin cytoskeleton rearrangements induced by MIM-B.
AB  - Numerous scaffold proteins coordinate signals from the environment with actin
      based protrusions during shape change and migration. Many scaffolds integrate
      signals from Rho-family GTPases to effect the assembly of specific actin
      structures. Here we investigate the mechanism of action MIM-B (missing in
      metastasis-B) on the actin cytoskeleton. MIM-B binds actin monomer through a WASP
      homology 2 motif, bundles actin filaments via an IRSp53/MIM domain, and is a long
      isoform of MIM, a proposed metastasis suppressor. We analysed the activity of MIM
      B toward the actin cytoskeleton as well as its potential link to cancer
      metastasis. Endogenous MIM-B protein is widely expressed and its expression is
      maintained in various metastatic cell lines. MIM-B induces lamellipodia-like
      actin-rich protrusions. The IRSp53/MIM domain of MIM-B, as well as Rac activity
      are required to induce protrusions, but not the WASP homology 2 motif. MIM-B
      binds and activates Rac via its IRSp53/MIM domain, but this is not sufficient to
      induce lamellipodia. Finally, our data revealed that actin bundling and Rac
      binding properties of MIM-B are not separable. Thus, MIM-B is unlikely to be a
      metastasis suppressor but acts as a scaffold protein that interacts with Rac,
      actin and actin-associated proteins to modulate lamellipodia formation.

PMID- 16280552
TI  - Tum/RacGAP50C provides a critical link between anaphase microtubules and the
      assembly of the contractile ring in Drosophila melanogaster.
AB  - A central question in understanding cytokinesis is how the cleavage plane is
      positioned. Although the positioning signal is likely to be transmitted via the
      anaphase microtubule array to the cell cortex, exactly how the microtubule array
      determines the site of contractile ring formation remains unresolved. By
      analysing tum/RacGAP50C mutant Drosophila embryos we show that cells lacking Tum
      do not form furrows and fail to localise the key cytokinetic components Pebble (a
      RhoGEF), Aurora B kinase, Diaphanous, Pav-KLP and Anillin. The GAP activity of
      Tum is required for cytokinesis: in its absence cytokinesis fails early even
      though Tum is present on microtubules at the cell equator where the furrow should
      form. Disruption of the Pebble-interacting domain leaves Tum localised to the
      cell equator on cortically associated microtubules, again with no evidence of
      furrowing. These data support a model in which Tum/RacGAP, via its interaction
      with Pbl, provides a critical link between the anaphase microtubule spindle and
      cytokinetic furrow formation in Drosophila cells.

PMID- 16280555
TI  - In-hospital formula supplementation of healthy breastfeeding newborns.
AB  - The UNICEF/WHO Baby-Friendly Hospital Initiative suggests that breastfeeding
      activities in hospital are important to later breastfeeding. Understanding
      reasons for in-hospital supplementation may help to optimize the successful
      implementation of this initiative. The objective was to identify predictors of in
      hospital initial formula supplementation of healthy, breastfeeding newborns. The
      authors analyzed 564 Canadian mother-infant pairs and interviewed nurses. Half of
      the study infants (47.9%) received formula in hospital; the median age at first
      supplementation was 8.4 hours. Risk for supplementation was affected by birth
      occurring between 7 PM and 9 AM (hazard ratio [HR] varied with time) and high
      maternal trait anxiety (HR=1.61, 95% confidence interval [CI]=1.01, 2.59). The
      following variables were protective against supplementation: planning to
      exclusively breastfeed (HR=0.46, 95% CI=0.33, 0.64), planning to breastfeed for
      >or=3 months (HR=0.56, 95% CI=0.37-0.86), childbirth education (HR=0.61, 95%
      CI=0.43, 0.86), mother born in Canada (HR=0.68, 95% CI=0.53, 0.87), completion of
      community college (HR=0.76, 95% CI=0.59, 0.98), male infant (HR=0.78, 95%
      CI=0.61, 0.99), and breastfeeding at delivery (HR varied with time). Nurses
      reported breastfeeding problems, infant behavior, and maternal fatigue as reasons
      for supplementing. Reassessing patterns of night feeds and encouraging
      breastfeeding at delivery may decrease supplementation. Trait anxiety reduction
      and the role of infant gender in supplementation merit further study.

PMID- 16280556
TI  - Indicators of effective breastfeeding and estimates of breast milk intake.
AB  - The authors tested indicators of effective breastfeeding to identify those that
      provide reliable estimates of human milk intake. Human milk intake of 82 full
      term infants was measured by test weights before and after feeding and compared
      with commonly used breastfeeding indicators: rooting, length of time before latch
      on, latch-on, suckle, observable swallowing, and audible swallowing. Two models
      were tested: model 1, describing indicators at 96 hours postpartum, and model 2,
      describing indicators at >96 hours postpartum. Median (interquartile) milliliters
      of mother's milk consumed per feeding was 26 ml (range, 4-47) at 96 hours and 54
      ml (range, 26-73) at >96 hours. Significant predictors of human milk intake in
      model 1 were rooting and observable swallowing (R2=26%, P<.01). In model 2,
      audible swallowing alone estimated human milk intake (R2=29%, P<.001). Observed
      swallowing and rooting during the first 4 days (96 hours) following birth and
      audible swallowing after that time should be included in the breastfeeding
      assessment of full-term infants.

PMID- 16280557
TI  - Human milk pumping rates of mothers of singletons and mothers of multiples.
AB  - Rates of breastfeeding are increasing, but the methods by which human milk is fed
      to infants is not well described. Using a retrospective survey design, the
      authors collected information about infant feeding from mothers of term, preterm,
      singleton, and multiple-gestation infants (n=346). Human milk feeding methods
      were characterized as solely at the breast, pumped only, or a combination. Sixty
      eight percent of mothers in the study fed their infants at least some human milk;
      77% of these mothers reported pumping milk. There was no difference in the
      percentage of pumping based on multiple gestation or length of pregnancy. Feeding
      human milk solely at the breast at early postpartum time points was associated
      with longer durations of human milk feeding overall. More research is needed to
      better understand why mothers choose pumping over direct human milk feedings and
      to evaluate the health outcomes associated with this practice.

PMID- 16280558
TI  - The use of ultrasound to characterize milk ejection in women using an electric
      breast pump.
AB  - This study aimed to use ultrasound imaging to investigate the milk ejection
      characteristics of women during a 10-minute expression using an electric breast
      pump capable of applying 2 markedly different vacuum patterns. The classic
      pattern (47 cycles/min) and 3-phase pattern (pre-milk ejection: 120 cycles/min,
      post-milk ejection: 20 cycles/min for 2 minutes post-milk ejection then 55-78
      cycles/min for 8 minutes) were tested, and the milk expressed was collected in 30
      second intervals. Multiple milk ejections (96%) were detected (classic: 3.27+/
      2.05; 3-phase: 3.72+/-1.19) and associated with increases in milk flow. Almost
      half of the total volume of milk expressed was removed during the first milk
      ejection (classic: 41.38+/-21.48%; 3-phase: 46.72+/-26.60%). There was no
      correlation between the number of milk ejections and both the total volume of
      milk and percentage of available milk for either pattern. In conclusion, milk
      ejection characteristics and efficiency of milk expression did not change in
      response to different expression patterns.

PMID- 16280559
TI  - Breastfeeding mothers' experiences using a supplemental feeding tube device:
      finding an alternative.
AB  - Strategies promoting initiation and successful continuation of breastfeeding are
      important in facilitating the breastfeeding experience. However, unique
      difficulties with breastfeeding may occur that necessitate specific
      interventions, to prevent early weaning and promote satisfaction with the
      breastfeeding experience. Special devices have been recommended and used to help
      women overcome various breastfeeding problems. A supplemental feeding tube device
      (SFTD) is a device that permits supplemental nourishment for infants while still
      preserving the breastfeeding goals of the mother. The purpose of this
      naturalistic study was to describe the experiences of breastfeeding mothers who
      used SFTDs to establish, reestablish, or supplement infant feeding at the breast.
      From the findings, 3 groups of themes emerged: seeking a solution, managing the
      challenges, and forming opinions. The underlying theme identified by all of the
      participants in the study was "finding an alternative." Women found the SFTD to
      be an acceptable alternative that facilitated their breastfeeding experience.

PMID- 16280560
TI  - Immunologic factors in human milk: the effects of gestational age and
      pasteurization.
AB  - This study compared concentrations of total protein, lysozyme, and
      immunoglobulins (IgA, IgG, IgM) in samples of colostrum (n=101) obtained from
      mothers of infants<32 weeks, 32 to 36(6) 7 weeks, and >or=37 weeks gestational
      age, both before and after pasteurization. Total protein was measured by
      refraction index, lysozyme by the lysoplate method, and immunoglobulins through
      the radial immunodiffusion technique. The total protein concentration was greater
      in colostrum of the <32 weeks and 32 to 36(6) 7 weeks categories compared to full
      term (P<.001), while concentrations of lysozyme and IgM were similar. IgA
      concentrations were higher in the <32 weeks group compared to the full-term and
      similar to the 32 to 36(6) 7 weeks group (P<.05). The IgG was higher in the <32
      weeks category compared to 32 to 36(6) 7 weeks, and both were similar to the full
      term (P<.05). Pasteurization significantly decreased all of the factors analyzed.

PMID- 16280562
TI  - Keeping abreast of the latest developments in lactation and breastfeeding:
      strategies for the lactation consultant.

PMID- 16280561
TI  - Symptoms of postpartum depression and breastfeeding.
AB  - Despite important health benefits, the presence of depressive symptoms may
      decrease the prevalence of breastfeeding. The current study assessed the
      relationship between depressive symptoms and breastfeeding at 6 and 12 weeks
      postpartum. Participants were recruited from a cohort completing a clinical trial
      of calcium for prevention of preeclampsia. At 6 weeks postpartum, the Edinburgh
      Postnatal Depression Scale (EPDS) was completed by mail. At 12 weeks postpartum,
      the EPDS was completed at an outpatient visit. There was an inverse relationship
      between depressive symptoms and breastfeeding at 6 weeks postpartum (P<.001) but
      not at 12 weeks. This relationship persisted even after controlling for prior
      history of depression, increased life stress, and current psychoactive
      medication. The results suggest that depressive symptoms early in the postpartum
      period may lower the prevalence of breastfeeding.

PMID- 16280563
TI  - A breastfeeding curriculum for residents and medical students: a
      multidisciplinary approach.
AB  - Medical school and residency training programs, in which practice patterns are
      established, frequently lack formal education in breastfeeding in the United
      States. This project, a curriculum based on the Wellstart Lactation Management
      Guide, was developed for resident physicians and medical students at the
      University of New Mexico to address the deficiency in formal education about
      breastfeeding. The curriculum, developed and implemented by faculty members from
      obstetrics/gynecology, pediatrics, and family medicine, includes formal
      interactive teaching sessions, discussion of breastfeeding issues on daily
      clinical rounds, and patient visits with lactation support personnel. Interns
      from the Departments of Pediatrics, Obstetrics/Gynecology, and Family Medicine
      participate. Surveys of participating residents and faculty demonstrate highly
      favorable attitudes. In conclusion, a multidisciplinary approach to breastfeeding
      education is feasible and well received by both teachers and residents.

PMID- 16280564
TI  - Feeding solid foods to your baby: what every parent should know.

PMID- 16280567
TI  - Not every graft has what it takes to attract a mossy fiber.

PMID- 16280568
TI  - The tuning properties of antennal lobe projection neurons.

PMID- 16280569
TI  - Brain microarray: finding needles in molecular haystacks.

PMID- 16280570
TI  - Neural circuitry underlying rule use in humans and nonhuman primates.

PMID- 16280572
TI  - Flashy science: controlling neural function with light.

PMID- 16280573
TI  - New neurons in the adult mammalian brain: synaptogenesis and functional
      integration.

PMID- 16280574
TI  - Time and the brain: how subjective time relates to neural time.
AB  - Most of the actions our brains perform on a daily basis, such as perceiving,
      speaking, and driving a car, require timing on the scale of tens to hundreds of
      milliseconds. New discoveries in psychophysics, electrophysiology, imaging, and
      computational modeling are contributing to an emerging picture of how the brain
      processes, learns, and perceives time.

PMID- 16280571
TI  - Lateralization of the vertebrate brain: taking the side of model systems.

PMID- 16280576
TI  - Wnt signaling in neural circuit development.

PMID- 16280575
TI  - The role of RNA and RNA processing in neurodegeneration.

PMID- 16280577
TI  - Epigenetic mechanisms and gene networks in the nervous system.

PMID- 16280578
TI  - Neurobiological mechanisms of the placebo effect.

PMID- 16280579
TI  - Activation in visual cortex correlates with the awareness of stereoscopic depth.
AB  - Using event-related functional magnetic resonance imaging, we studied the
      activation correlating with the awareness of stereoscopic depth using a bistable
      slanted surface (slant rivalry). Bistability resulted from incongruence between
      two slant-defining cues: binocular disparity and monocular perspective. The
      stimulus was perceived as alternating between the perspective-dominated percept
      (monocular depth) and the disparity-dominated percept (stereopsis), while sensory
      input remained constant, enabling us to study changes in awareness of depth
      associated with either cue. Transient activation relating to perceptual
      alternations was found bilaterally in the caudal part of the intraparietal
      sulcus, in the right-hemispheric anterior intraparietal sulcus, within visual
      area V4d-topo, and inferior to area MT+. Transient activation correlating
      specifically with alternations toward the disparity-dominated percept was found
      in a number of visual areas, including dorsal visual areas V3A, V7, and V4d-topo
      and visual areas MT+ and lateral occipital complex. No activation was found for
      alternations toward the perspective-dominated percept. Our results show that of
      all visual areas responsive to disparity-defined depth, V4d-topo shows the most
      robust signal changes correlating with the instigation of stereoscopic depth
      awareness (stereopsis).

PMID- 16280580
TI  - Interactions between metabotropic glutamate 5 and adenosine A2A receptors in
      normal and parkinsonian mice.
AB  - Evidence for heteromeric receptor complexes comprising adenosine A2A and
      metabotropic glutamate 5 (mGlu5) receptors in striatum has raised the possibility
      of synergistic interactions between striatal A2A and mGlu5 receptors. We
      investigated the role of striatal A2A receptors in the locomotor stimulant and
      antiparkinsonian properties of mGlu5 antagonists using complementary
      pharmacologic and genetic approaches. Locomotion acutely stimulated by the mGlu5
      antagonist [2-methyl-6-(phenylethynyl)-pyridine (MPEP)] was absent in mGlu5 knock
      out (KO) mice and was potentiated by an A2A antagonist KW-6002 [(E)-1,3-diethyl-8
      (3,4-dimethoxystyryl)-7-methylxanthine], both in normal and in dopamine-depleted
      (reserpinized) mice. Conversely, the MPEP-induced motor response was markedly
      attenuated in single and double A2A and D2 receptor KO mice. In contrast, motor
      stimulation by a D1 dopamine agonist was not attenuated in the KO mice. The A2A
      receptor dependence of MPEP-induced motor stimulation was investigated further
      using a postnatal forebrain-specific conditional (Cre/loxP system) KO of the A2A
      receptor. MPEP loses the ability to stimulate locomotion in conditional KO mice,
      suggesting that this mGlu5 antagonist effect requires the postdevelopmental
      action of striatal A2A receptors. The potentiation of mGlu5 antagonist-induced
      motor stimulation by an A2A antagonist and its dependence on both D2 and
      forebrain A2A receptors highlight the functional interdependence of these
      receptors. These data also strengthen a rationale for pursuing a combinational
      drug strategy for enhancing the antiparkinsonian effects of A2A and mGlu5
      antagonists.

PMID- 16280581
TI  - Neural activity in macaque parietal cortex reflects temporal integration of
      visual motion signals during perceptual decision making.
AB  - Decision-making often requires the accumulation and maintenance of evidence over
      time. Although the neural signals underlying sensory processing have been studied
      extensively, little is known about how the brain accrues and holds these sensory
      signals to guide later actions. Previous work has suggested that neural activity
      in the lateral intraparietal area (LIP) of the monkey brain reflects the
      formation of perceptual decisions in a random dot direction-discrimination task
      in which monkeys communicate their decisions with eye-movement responses. We
      tested the hypothesis that decision-related neural activity in LIP represents the
      time integral of the momentary motion "evidence." By briefly perturbing the
      strength of the visual motion stimulus during the formation of perceptual
      decisions, we tested whether this LIP activity reflected a persistent, integrated
      "memory" of these brief sensory events. We found that the responses of LIP
      neurons reflected substantial temporal integration. Brief pulses had persistent
      effects on both the monkeys' choices and the responses of neurons in LIP, lasting
      up to 800 ms after appearance. These results demonstrate that LIP is involved in
      neural time integration underlying the accumulation of evidence in this task.
      Additional analyses suggest that decision-related LIP responses, as well as
      behavioral choices and reaction times, can be explained by near-perfect time
      integration that stops when a criterion amount of evidence has been accumulated.
      Temporal integration may be a fundamental computation underlying higher cognitive
      functions that are dissociated from immediate sensory inputs or motor outputs.

PMID- 16280583
TI  - Localization and identification of concurrent sounds in the owl's auditory space
      map.
AB  - In nature, sounds from multiple sources sum at the eardrums, generating complex
      cues for sound localization and identification. In this clutter, the auditory
      system must determine "what is where." We examined this process in the auditory
      space map of the barn owl's (Tyto alba) inferior colliculus using two spatially
      separated sources simultaneously emitting uncorrelated noise bursts, which were
      uniquely identified by different frequencies of sinusoidal amplitude modulation.
      Spatial response profiles of isolated neurons were constructed by testing the
      source-pair centered at various locations in virtual auditory space. The neurons
      responded whenever a source was placed within the receptive field, generating two
      clearly segregated foci of activity at appropriate loci. The spike trains were
      locked strongly to the amplitude modulation of the source within the receptive
      field, whereas the other source had minimal influence. Two sources amplitude
      modulated at the same rate were resolved successfully, suggesting that source
      separation is based on differences of fine structure. The spike rate and
      synchrony were stronger for whichever source had the stronger average binaural
      level. A computational model showed that neuronal activity was primarily
      proportional to the degree of matching between the momentary binaural cues and
      the preferred values of the neuron. The model showed that individual neurons
      respond to and synchronize with sources in their receptive field if there are
      frequencies having an average binaural-level advantage over a second source.
      Frequencies with interaural phase differences that are shared by both sources may
      also evoke activity, which may be synchronized with the amplitude modulations
      from either source.

PMID- 16280582
TI  - Migration from a mitogenic niche promotes cell-cycle exit.
AB  - During development, neural precursors proliferate in one location and migrate to
      the residence of their mature function. The transition from a proliferative stage
      to a migratory stage is a critical juncture; errors in this process may result in
      tumor formation, mental retardation, or epilepsy. This transition could be the
      result of a simple sequential process in which precursors exit the cell cycle and
      then begin to migrate or a dynamically regulated process in which migration away
      from a mitogenic niche induces precursors to exit the cell cycle. Here, we show,
      using in vivo and in vitro approaches, that granule cell precursors proliferate
      when they are exposed to the microenvironment of the external granule cell layer
      (EGL) and exit the cell cycle as a result of migrating away from this
      environment. In vivo, granule cell precursors that remain in the EGL because of
      impaired migration continue to proliferate in the mitogenic niche of the EGL. In
      vitro, granule cell precursors that are introduced into an organotypic cerebellar
      slice proliferate preferentially in the EGL. We identify Sonic Hedgehog as a
      critical component of the EGL mitogenic niche. Together, these data indicate that
      migration away from a mitogenic niche promotes transition from a proliferative to
      a nonproliferative, migratory stage.

PMID- 16280584
TI  - Kinetics and spontaneous open probability conferred by the epsilon subunit of the
      GABAA receptor.
AB  - GABAA receptors mediate synaptic and extrasynaptic inhibition. Native receptors
      consist of alpha and beta subunits, which are required for function, and another
      "modulatory" subunit, for example, gamma, delta, or epsilon. Of these, the
      epsilon subunit has the most restricted distribution, confers resistance to
      neurosteroid and anesthetic modulation, and causes spontaneous channel opening.
      Little is known, however, about how epsilon affects receptor kinetics, which in
      turn shape responses to both ambient and synaptic GABA exposure. Here, we
      expressed human alpha2beta1, alpha2beta1gamma2, or alpha2beta1epsilon subunit
      combinations in human embryonic kidney 293 cells and used rapid solution exchange
      to study receptor kinetics in outside-out patches. The epsilon subunit greatly
      slowed deactivation and recovery after brief GABA pulses. During long, saturating
      GABA pulses, the rate of desensitization was slower for alpha2beta1epsilon and
      alpha2beta1gamma2 than for alpha2beta1. However, in alpha2beta1epsilon, the final
      extent of desensitization was large compared with that of alpha2beta1gamma2.
      Responses in alpha2beta1epsilon, but not the others, were often followed by an
      "overshoot" above the baseline, suggesting that a fraction of channels are
      spontaneously open and are transiently silenced by receptor activation and
      subsequent desensitization. The baseline current and associated noise were
      reduced by picrotoxin, revealing that epsilon-containing channels are open
      approximately 4% of the time in the absence of GABA. These results suggest that,
      if epsilon-containing receptors are expressed at synapses, the synaptic currents
      would be long-lasting but may rundown quickly under high-frequency activation. In
      addition, silencing of spontaneous openings by desensitization raises the
      possibility that tonic inhibition mediated by epsilon-containing receptors may be
      regulated by phasic inhibition.

PMID- 16280585
TI  - Gephyrin regulates the cell surface dynamics of synaptic GABAA receptors.
AB  - The efficacy of fast synaptic inhibition is critically dependent on the
      accumulation of GABAA receptors at inhibitory synapses, a process that remains
      poorly understood. Here, we examined the dynamics of cell surface GABAA receptors
      using receptor subunits modified with N-terminal extracellular ecliptic pHluorin
      reporters. In hippocampal neurons, GABAA receptors incorporating pHluorin-tagged
      subunits were found to be clustered at synaptic sites and also expressed as
      diffuse extrasynaptic staining. By combining FRAP (fluorescence recovery after
      photobleaching) measurements with live imaging of FM4-64-labeled active
      presynaptic terminals, it was evident that clustered synaptic receptors exhibit
      significantly lower rates of mobility at the cell surface compared with their
      extrasynaptic counterparts. To examine the basis of this confinement, we used
      RNAi to inhibit the expression of gephyrin, a protein shown to regulate the
      accumulation of GABAA receptors at synaptic sites. However, whether gephyrin acts
      to control the actual formation of receptor clusters, their stability, or is
      simply a global regulator of receptor cell surface number remains unknown.
      Inhibiting gephyrin expression did not modify the total number of GABAA receptors
      expressed on the neuronal cell surface but significantly decreased the number of
      receptor clusters. Live imaging revealed that clusters that formed in the absence
      of gephyrin were significantly more mobile compared with those in control
      neurons. Together, our results demonstrate that synaptic GABAA receptors have
      lower levels of lateral mobility compared with their extrasynaptic counterparts,
      and suggest a specific role for gephyrin in reducing the diffusion of GABAA
      receptors, facilitating their accumulation at inhibitory synapses.

PMID- 16280586
TI  - Src-family kinases stabilize the neuromuscular synapse in vivo via protein
      interactions, phosphorylation, and cytoskeletal linkage of acetylcholine
      receptors.
AB  - Postnatal stabilization and maturation of the postsynaptic membrane are important
      for development and function of the neuromuscular junction (NMJ), but the
      underlying mechanisms remain poorly characterized. We examined the role of Src
      family kinases (SFKs) in vivo. Electroporation of kinase-inactive Src constructs
      into soleus muscles of adult mice caused NMJ disassembly: acetylcholine receptor
      (AChR)-rich areas became fragmented; the topology of nerve terminal, AChRs, and
      synaptic nuclei was disturbed; and occasionally nerves started to sprout.
      Electroporation of kinase-overactive Src produced similar but milder effects. We
      studied the mechanism of SFK action using cultured src(-/-);fyn(-/-) myotubes,
      focusing on clustering of postsynaptic proteins, their interaction with AChRs,
      and AChR phosphorylation. Rapsyn and the utrophin-glycoprotein complex were
      recruited normally into AChR-containing clusters by agrin in src(-/-);fyn(-/-)
      myotubes. But after agrin withdrawal, clusters of these proteins disappeared
      rapidly in parallel with AChRs, revealing that SFKs are of general importance in
      postsynaptic stability. At the same time, AChR interaction with rapsyn and
      dystrobrevin and AChR phosphorylation decreased after agrin withdrawal from
      mutant myotubes. Unexpectedly, levels of rapsyn protein were increased in src(-/
      );fyn(-/-) myotubes, whereas rapsyn-cytoskeleton interactions were unaffected.
      The overall cytoskeletal link of AChRs was weak but still strengthened by agrin
      in mutant cells, consistent with the normal formation but decreased stability of
      AChR clusters. These data show that correctly balanced activity of SFKs is
      critical in maintaining adult NMJs in vivo. SFKs hold the postsynaptic apparatus
      together through stabilization of AChR-rapsyn interaction and AChR
      phosphorylation. In addition, SFKs control rapsyn levels and AChR-cytoskeletal
      linkage.

PMID- 16280587
TI  - Event-related brain potential correlates of human auditory sensory memory-trace
      formation.
AB  - The event-related potential (ERP) component mismatch negativity (MMN) is a neural
      marker of human echoic memory. MMN is elicited by deviant sounds embedded in a
      stream of frequent standards, reflecting the deviation from an inferred memory
      trace of the standard stimulus. The strength of this memory trace is thought to
      be proportional to the number of repetitions of the standard tone, visible as the
      progressive enhancement of MMN with number of repetitions (MMN memory-trace
      effect). However, no direct ERP correlates of the formation of echoic memory
      traces are currently known. This study set out to investigate changes in ERPs to
      different numbers of repetitions of standards, delivered in a roving-stimulus
      paradigm in which the frequency of the standard stimulus changed randomly between
      stimulus trains. Normal healthy volunteers (n = 40) were engaged in two
      experimental conditions: during passive listening and while actively
      discriminating changes in tone frequency. As predicted, MMN increased with
      increasing number of standards. However, this MMN memory-trace effect was caused
      mainly by enhancement with stimulus repetition of a slow positive wave from 50 to
      250 ms poststimulus in the standard ERP, which is termed here "repetition
      positivity" (RP). This RP was recorded from frontocentral electrodes when
      participants were passively listening to or actively discriminating changes in
      tone frequency. RP may represent a human ERP correlate of rapid and stimulus
      specific adaptation, a candidate neuronal mechanism underlying sensory memory
      formation in the auditory cortex.

PMID- 16280588
TI  - Silencing primary dystonia: lentiviral-mediated RNA interference therapy for DYT1
      dystonia.
AB  - DYT1 is the most common inherited dystonia. Currently, there are no preventive or
      curative therapies for this dominantly inherited disease. DYT1 dystonia is caused
      by a common three-nucleotide deletion in the TOR1A gene that eliminates a
      glutamic acid residue from the protein torsinA. Recent studies suggest that
      torsinA carrying the disease-linked mutation, torsinA(DeltaE) acts through a
      dominant-negative effect by recruiting wild-type torsinA [torsinA(wt)] into
      oligomeric structures in the nuclear envelope. Therefore, suppressing
      torsinA(DeltaE) expression through RNA interference (RNAi) could restore the
      normal function of torsinA(wt), representing a potentially effective therapy
      regardless of the biological role of torsinA. Here, we have generated short
      hairpin RNAs (shRNAs) that mediate allele-specific suppression of torsinA(DeltaE)
      and rescue cells from its dominant-negative effect, restoring the normal
      distribution of torsinA(wt). In addition, delivery of this shRNA by a recombinant
      feline immunodeficiency virus effectively silenced torsinA(DeltaE) in a neural
      model of the disease. We further establish the feasibility of this viral-mediated
      RNAi approach by demonstrating significant suppression of endogenous torsinA in
      mammalian neurons. Finally, this silencing of torsinA is achieved without
      triggering an interferon response. These results support the potential use of
      viral-mediated RNAi as a therapy for DYT1 dystonia and establish the basis for
      preclinical testing in animal models of the disease.

PMID- 16280589
TI  - Peptide YY(3-36) inhibits both anorexigenic proopiomelanocortin and orexigenic
      neuropeptide Y neurons: implications for hypothalamic regulation of energy
      homeostasis.
AB  - Peptide YY(3-36) (PYY(3-36)) is released by endocrine cells of the gut and may
      serve as an important long-distance neuropeptide signal relating energy balance
      information to the brain to depress food intake. The postulated mechanism is the
      activation of anorexigenic proopiomelanocortin (POMC) neurons of the hypothalamic
      arcuate nucleus. In striking contrast, using voltage and current-clamp recording,
      we found that PYY(3-36) consistently, dose dependently, and reversibly inhibited
      POMC cells by reducing action potentials, hyperpolarizing the membrane potential,
      decreasing input resistance and inward calcium currents, increasing G-protein
      gated inwardly rectifying K+ channel currents, and presynaptically inhibiting
      release of excitatory glutamate. Importantly, we found PYY(3-36) had similar
      inhibitory effects on identified orexigenic neuropeptide Y (NPY) neurons. In both
      cell types, these effects were blocked by BIIE0246, a Y2 receptor antagonist.
      Together, these data argue that anorexigenic actions of PYY(3-36) are mediated
      more likely by inhibition of NPY neurons. Dual PYY(3-36) inhibition of both NPY
      and POMC cells may temporarily reduce the contribution of arcuate cells to
      feeding circuits, enhancing the role of other CNS loci.

PMID- 16280590
TI  - Metabotropic glutamate receptor 8-expressing nerve terminals target subsets of
      GABAergic neurons in the hippocampus.
AB  - Presynaptic metabotropic glutamate receptors (mGluRs) show a highly selective
      expression and subcellular location in nerve terminals modulating
      neurotransmitter release. We have demonstrated that alternatively spliced
      variants of mGluR8, mGluR8a and mGluR8b, have an overlapping distribution in the
      hippocampus, and besides perforant path terminals, they are expressed in the
      presynaptic active zone of boutons making synapses selectively with several types
      of GABAergic interneurons, primarily in the stratum oriens. Boutons labeled for
      mGluR8 formed either type I or type II synapses, and the latter were GABAergic.
      Some mGluR8-positive boutons also expressed mGluR7 or vasoactive intestinal
      polypeptide. Interneurons strongly immunopositive for the muscarinic M2 or the
      mGlu1 receptors were the primary targets of mGluR8-containing terminals in the
      stratum oriens, but only neurochemically distinct subsets were innervated by
      mGluR8-enriched terminals. The majority of M2-positive neurons were mGluR8
      innervated, but a minority, which expresses somatostatin, was not. Rare neurons
      coexpressing calretinin and M2 were consistently targeted by mGluR8-positive
      boutons. In vivo recording and labeling of an mGluR8-decorated and strongly M2
      positive interneuron revealed a trilaminar cell with complex spike bursts during
      theta oscillations and strong discharge during sharp wave/ripple events. The
      trilaminar cell had a large projection from the CA1 area to the subiculum and a
      preferential innervation of interneurons in the CA1 area in addition to pyramidal
      cell somata and dendrites. The postsynaptic interneuron type-specific expression
      of the high-efficacy presynaptic mGluR8 in both putative glutamatergic and in
      identified GABAergic terminals predicts a role in adjusting the activity of
      interneurons depending on the level of network activity.

PMID- 16280591
TI  - Dopamine modulation of state-dependent endocannabinoid release and long-term
      depression in the striatum.
AB  - Endocannabinoids are important mediators of short- and long-term synaptic
      plasticity, but the mechanisms of endocannabinoid release have not been studied
      extensively outside the hippocampus and cerebellum. Here, we examined the
      mechanisms of endocannabinoid-mediated long-term depression (eCB-LTD) in the
      dorsal striatum, a brain region critical for motor control and reinforcement
      learning. Unlike other cell types, strong depolarization of medium spiny neurons
      was not sufficient to yield detectable endocannabinoid release. However, when
      paired with postsynaptic depolarization sufficient to activate L-type calcium
      channels, activation of postsynaptic metabotropic glutamate receptors (mGluRs),
      either by high-frequency tetanic stimulation or an agonist, induced eCB-LTD.
      Pairing bursts of afferent stimulation with brief subthreshold membrane
      depolarizations that mimicked down-state to up-state transitions also induced eCB
      LTD, which not only required activation of mGluRs and L-type calcium channels but
      also was bidirectionally modulated by dopamine D2 receptors. Consistent with
      network models, these results demonstrate that dopamine regulates the induction
      of a Hebbian form of long-term synaptic plasticity in the striatum. However, this
      gating of plasticity by dopamine is accomplished via an unexpected mechanism
      involving the regulation of mGluR-dependent endocannabinoid release.

PMID- 16280593
TI  - Central and peripheral axon branches from one neuron are guided differentially by
      Semaphorin3D and transient axonal glycoprotein-1.
AB  - For multiple axons from one neuron to extend in different directions to unique
      targets, the growth cones of each axon must have distinct responses to guidance
      cues. However, the mechanisms by which separate axon branches are guided along
      different pathways are mainly unknown. Zebrafish Rohon-Beard (R-B) sensory
      neurons extend central axon branches in the spinal cord and peripheral axons to
      the epidermis. To investigate the differential guidance mechanisms of the central
      versus peripheral R-B axon branches, we used live-growth cone imaging in vivo
      combined with manipulation of individual guidance molecules. We show that a
      semaphorin expressed at the dorsal spinal cord midline, Semaphorin3D (Sema3D),
      may act to repel the peripheral axons out of the spinal cord. Sema3D knock-down
      reduces the number of peripheral axons. Remarkably, Sema3D ectopic expression
      repels and induces branching of peripheral axons in vivo but has no effect on
      central axons from the same neurons. Conversely, central axons require a growth
      promoting molecule, transient axonal glycoprotein-1 (TAG-1), to advance, whereas
      peripheral axons do not. After TAG-1 knock-down, central growth cones display
      extensive protrusive activity but make little forward advance. TAG-1 knock-down
      has no effect on the motility or advance of peripheral growth cones. These
      experiments show how Sema3D and TAG-1 regulate the motility and behavior of
      growth cones extending in their natural in vivo environment and demonstrate that
      two different axon branches from one neuron respond differently to guidance cues
      in vivo.

PMID- 16280592
TI  - The role of Snapin in neurosecretion: snapin knock-out mice exhibit impaired
      calcium-dependent exocytosis of large dense-core vesicles in chromaffin cells.
AB  - Identification of the molecules that regulate the priming of synaptic vesicles
      for fusion and the structural coupling of the calcium sensor with the soluble N
      ethyl maleimide sensitive factor adaptor protein receptor (SNARE)-based fusion
      machinery is critical for understanding the mechanisms underlying calcium
      dependent neurosecretion. Snapin binds to synaptosomal-associated protein 25 kDa
      (SNAP-25) and enhances the association of the SNARE complex with synaptotagmin.
      In the present study, we abolished snapin expression in mice and functionally
      evaluated the role of Snapin in neuroexocytosis. We found that the association of
      synaptotagmin-1 with SNAP-25 in brain homogenates of snapin mutant mice is
      impaired. Consequently, the absence of Snapin in embryonic chromaffin cells leads
      to a significant reduction of calcium-dependent exocytosis resulting from a
      decreased number of vesicles in releasable pools. Overexpression of Snapin fully
      rescued this inhibitory effect in the mutant cells. Furthermore, Snapin is
      relatively enriched in the purified large dense-core vesicles of chromaffin cells
      and associated with synaptotagmin-1. Thus, our biochemical and
      electrophysiological studies using snapin knock-out mice demonstrate that Snapin
      plays a critical role in modulating neurosecretion by stabilizing the release
      ready vesicles.

PMID- 16280595
TI  - Analysis of microarray studies performed in the neurosciences.
AB  - The application of microarray technology to basic and applied fields of science
      has been progressing rapidly and broadly since its initial description. The field
      of neuroscience stands to benefit particularly, as nervous tissue is the most
      transcriptionally active system within most biological organisms. Moreover, large
      numbers of cell and animal models have been created that mimic many biochemical
      and behavioral features of neurological states and diseases. In the present
      study, data on study designs, tissue sources, technology platforms, bioinformatic
      tools, and results obtained from 448 published microarray studies were collected.
      The data were then summarized to determine overall usage statistics of
      microarrays. Future directions and applications for microarrays in the
      neurosciences were then inferred from the data analyzed.

PMID- 16280594
TI  - Touching a rubber hand: feeling of body ownership is associated with activity in
      multisensory brain areas.
AB  - In the "rubber-hand illusion," the sight of brushing of a rubber hand at the same
      time as brushing of the person's own hidden hand is sufficient to produce a
      feeling of ownership of the fake hand. We shown previously that this illusion is
      associated with activity in the multisensory areas, most notably the ventral
      premotor cortex (Ehrsson et al., 2004). However, it remains to be demonstrated
      that this illusion does not simply reflect the dominant role of vision and that
      the premotor activity does not reflect a visual representation of an object near
      the hand. To address these issues, we introduce a somatic rubber-hand illusion.
      The experimenter moved the blindfolded participant's left index finger so that it
      touched the fake hand, and simultaneously, he touched the participant's real
      right hand, synchronizing the touches as perfectly as possible. After
      approximately 9.7 s, this stimulation elicited an illusion that one was touching
      one's own hand. We scanned brain activity during this illusion and two control
      conditions, using functional magnetic resonance imaging. Activity in the ventral
      premotor cortices, intraparietal cortices, and the cerebellum was associated with
      the illusion of touching one's own hand. Furthermore, the rated strength of the
      illusion correlated with the degree of premotor and cerebellar activity. This
      finding suggests that the activity in these areas reflects the detection of
      congruent multisensory signals from one's own body, rather than of visual
      representations. We propose that this could be the mechanism for the feeling of
      body ownership.

PMID- 16280596
TI  - Microarray and real-time PCR analyses of gene expression in the honeybee brain
      following caffeine treatment.
AB  - To test the idea that caffeine might induce changes in gene expression in the
      honeybee brain, we contrasted the transcriptional profiles of control and
      caffeine-treated brains using high-throughput cDNA microarrays. Additional
      quantitative real-time PCR was performed on a subset of eight transcripts to
      visualize the temporal changes induced by caffeine. Genes that were significantly
      upregulated in caffeine-treated brains included those involved in synaptic
      signaling (GABA:Na symporter, dopamine D2R-like receptor, and synapsin),
      cytoskeletal modifications (kinesin and microtubule motors), protein translation
      (ribosomal protein RpL4, elongation factors), and calcium-dependent processes
      (calcium transporter, calmodulin- dependent cyclic nucleotide phosphodiesterase).
      In addition, our study uncovered a number of novel, caffeine-inducible genes that
      appear to be unique to the honeybee. Time-dependent profiling of caffeine
      sensitive gene expression shows significant upregulation 1 h after treatment
      followed by moderate downregulation after 4 h with no additional changes occuring
      after 24 h. Our results provide initial evidence that the dopaminergic system and
      calcium exchange are the main targets of caffeine in the honeybee brain and
      suggest that molecular responses to caffeine in an invertebrate brain are similar
      to those in vertebrate organisms.

PMID- 16280597
TI  - Increased vulnerability to L-DOPA toxicity in dopaminergic neurons From VMAT2
      heterozygote knockout mice.
AB  - Parkinson's disease (PD) is characterized by a preferential loss of dopaminergic
      neurons in the substantia nigra pars compacta. The etiology of PD remains
      unclear; however, generation of reactive oxygen species during oxidation of free
      dopamine (DA) in the cytoplasm might be one of the causes of selective
      dopaminergic neuron loss in PD. Vesicular monoamine transporter type 2 (VMAT2)
      proteins in nerve terminals take up and partition DA from neuronal cytoplasm into
      synaptic vesicles. Alterations of VMAT2 function might therefore cause
      cytoplasmic accumulation of free DA, which is toxic for dopaminergic neurons. We
      showed that dopaminergic neurons from VMAT2 heterozygous knockout mice were more
      vulnerable to the toxic effect of L-3, 4-dihydroxyphenylalanine (L-DOPA, a DA
      precursor) than those from wild-type mice. Our results suggest that reduction of
      VMAT2 activity might attenuate the efficacy of L-DOPA therapy for patients with
      PD.

PMID- 16280598
TI  - Phox2 and dHAND transcription factors select shared and unique target genes in
      the noradrenergic cell type.
AB  - The noradrenergic cell type is characterized by the expression of proteins
      involved in the biosynthesis, transport, and secretion of noradrenaline and is
      dependent on the sequential and combinatorial expression of numerous
      transcription factors, including Phox2a, Phox2b, dHAND, GATA2, GATA3, and MASH1.
      Phox2a and Phox2b transactivate the promoter of the gene encoding the
      noradrenergic biosynthetic enzyme, dopamine beta-hydroxylase (DBH), and dHAND
      potentiates the activity of Phox2a. In this study, we use chromatin
      immunoprecipitation assays to identify target genes of the Phox2 proteins and
      dHAND. All three proteins are bound to the DBH and PHOX2B promoter regions in SH
      SY5Y neuroblastoma cells. The interaction between Phox2a and dHAND is analyzed by
      fluorescent anisotropy, which demonstrates that dHAND causes an eightfold
      increase in the affinity of Phox2a for its recognition sites on the DBH promoter
      region. The Phox2 proteins are not found on the genes encoding other
      noradrenergic enzymatic or transport proteins but are reciprocally bound to each
      other's promoters in SH-SY5Y cells. Together with Phox2a and Phox2b, dHAND is
      bound to the PHOX2B promoter and is also associated with the GATA2 and eHAND
      genes in the absence of the Phox2 proteins. These results demonstrate the direct
      interactions of the Phox2 and dHAND transcription factors within a noradrenergic
      cell type. The Phox2 proteins were found to share all target genes, whereas dHAND
      binds to genes independently of Phox2a.

PMID- 16280599
TI  - High salt culture conditions suppress proliferation of rat C6 glioma cell by
      arresting cell-cycle progression at S-phase.
AB  - As one of the in vitro model experiments for investigating a possible effect of
      extracellular environmental stresses on glial cell proliferation, the influence
      of high salt culture conditions on the growth of rat C6 glioma cells was
      examined. Exposure to the culture medium containing high concentrations of NaCl
      reduced the number of viable cells in a concentration-dependent manner without
      any significant change in their viability. In contrast, proliferation of these
      cells was not substantially altered by culturing them in hyperosmotic medium
      containing either sucrose or glycerol, both of which were osmotically almost
      equivalent to high salt culture medium. On the other hand, expression of the egr
      1 gene, an immediate early gene related to the proliferation and differentiation
      of various cells, was enhanced by culturing glioma cells in high salt medium
      while the reduction of glial fibrillary acidic protein content, an index of glial
      cell differentiation, was observed under the same culture conditions. Further
      studies on the relationship between egr-1 gene expression and the cell cycle
      showed that cell-cycle progression was arrested at S-phase by culturing glioma
      cells in high salt medium. Moreover, both resveratrol and CPT-11, which are known
      to arrest cell-cycle progression, elevated egr-1 mRNA levels in glioma cells.
      Thus, these observations suggest that high salt culture conditions might suppress
      the proliferation of rat C6 glioma cells as a consequence of arresting cell-cycle
      progression at S-phase, resulting secondarily in the compensatory enhancement of
      egr-1 gene expression.

PMID- 16280601
TI  - No evidence for association between dyslexia and DYX1C1 functional variants in a
      group of children and adolescents from Southern Italy.
AB  - Recently, DYX1C1, a candidate gene for developmental dyslexia, encoding a nuclear
      tetratricopeptide repeat domain protein dynamically regulated in brain, has been
      characterized through a translocation breakpoint in a Finnish family. Two
      putatively functional variants, -3G/A and 1249G/T, have been reported to be
      significantly associated with dyslexia in this population. Further studies,
      conducted on different ethnic groups (English and Canadian), have not confirmed a
      role for DYX1C1 variants in increasing the risk for dyslexia. We investigated the
      role of these variants in dyslexic children and adolescents from Southern Italy.
      No significant evidence for association between dyslexia and these DYX1C1
      putative functional variants has been shown. We argue that the different DYX1C1
      allele frequencies shown among Italian and Finnish subjects with dyslexia could
      be attributable to the different linkage disequilibrium structure of these
      populations.

PMID- 16280600
TI  - Regional distribution of the prostaglandin E2 receptor EP1 in the rat brain:
      accumulation in Purkinje cells of the cerebellum.
AB  - Prostaglandin E2 (PGE2), is a major prostanoid produced by the activity of
      cyclooxygenases (COX) in response to various physiological and pathological
      stimuli. PGE2 exerts its effects by activating four specific E-type prostanoid
      receptors (EP1, EP2, EP3, and EP4). In the present study, we analyzed the
      expression of the PGE2 receptor EP1 (mRNA and protein) in different regions of
      the adult rat brain (hippocampus, hypothalamus, striatum, prefrontal cerebral
      cortex, parietal cortex, brain stem, and cerebellum) using reverse transcription-
      polymerase chain reaction, Western blotting, and immunohistochemical methods. On
      a regional basis, levels of EP1 mRNA were the highest in parietal cortex and
      cerebellum. At the protein level, we found very strong expression of EP1 in
      cerebellum, as revealed by Western blotting experiments. Furthermore, the present
      study provides for the first time evidence that the EP1 receptor is highly
      expressed in the cerebellum, where the Purkinje cells displayed very high
      immunolabeling of their perikaryon and dendrites, as observed in the
      immunohistochemical analysis. Results from the present study indicate that the
      EP1 prostanoid receptor is expressed in specific neuronal populations, which
      possibly determine the region-specific response to PGE2.

PMID- 16280602
TI  - Anti-fibroblast growth factor-2 antibodies attenuate mechanical allodynia in a
      rat model of neuropathic pain.
AB  - Peripheral nerve injury leads to the activation of spinal cord astrocytes, which
      contribute to maintaining neuropathic (NP) pain behavior. Fibroblast growth
      factor-2 (FGF-2), a neurotrophic and gliogenic factor, is upregulated by spinal
      cord astrocytes in response to ligation of spinal nerves L5 and L6 (spinal nerve
      ligation [SpNL]). To evaluate the contribution of spinal astroglial FGF-2 to
      mechanical allodynia following SpNL, neutralizing antibodies to FGF-2 were
      injected intrathecally. Administration of 18 microg of anti-FGF-2 antibodies
      attenuated mechanical allodynia at day 21 after SpNL and reduced FGF-2 and glial
      acidic fibrillary protein mRNA expression and immunoreactivity in the L5 spinal
      cord segment of rats with SpNL. These results suggest that endogenous astroglial
      FGF-2 contributes to maintaining NP tactile allodynia associated with reactivity
      of spinal cord astrocytes and that inhibition of spinal FGF-2 ameliorates NP pain
      signs.

PMID- 16280603
TI  - Effect of amyloid peptides on the increase in TrkA receptor expression induced by
      nicotine in vitro and in vivo.
AB  - The ability of nicotine to induce a cytoprotective or neuroprotective action
      occurs through several downstream mechanisms. One possibility is that the drug
      increases the expression of tyrosine kinase A (TrkA) nerve growth factor (NGF)
      receptors. Certain beta-amyloid peptides (e.g., Abeta1-42) have been shown to
      bind with high affinity to alpha7 nicotinic receptors and thus interfere with a
      potentially neurotrophic influence. Treatment of differentiated PC-12 cells with
      nicotine produced a concentration-dependent increase in cell-surface TrkA
      receptors that occurred concomitantly with cytoprotection. The effect of nicotine
      was blocked by either of the alpha7 receptor antagonists alpha-bungarotoxin
      (alpha-BTX) or methyllycaconatine. The cytoprotective action of nicotine also was
      inhibited by pretreatment with 10-100 nM Abeta1-42. Nicotine also was
      administered (four injections of 30 microg, spaced evenly over 24 h) to rats by
      direct injection into a lateral cerebral ventricle. Brain TrkA expression was
      increased significantly in hippocampus and entorhinal cortex (up to 32% above
      control), with no changes found in cerebral cortex or hypothalamus. The nicotine
      induced increases in TrKA expression in hippocampus and entorhinal cortex were
      significantly inhibited by 10 microg alpha-BTXor by 10 nmol Abeta1-42. Therefore,
      physiologically relevant concentrations of Abeta1-42 can prevent nicotine-induced
      TrkA receptor expression in brain regions containing cholinergic neurons
      susceptible to the neurotoxicity associated with Alzheimer's disease.

PMID- 16280607
TI  - Letter to the editor: outbreaks caused by parvovirus B19.

PMID- 16280605
TI  - Mouse brain synaptosomes accumulate copper-67 efficiently by two distinct
      processes independent of cellular prion protein.
AB  - The prion protein (PrPC) is a copper-binding, cell-surface protein that plays an
      essential role in the etiology of transmissible spongiform encephalopathies.
      Atomic absorption spectroscopy studies have established that synaptosomal copper
      content is reduced in PrPC-deficient mice as compared with wild-type (WT) or PrP-
      overexpressing mice. To address the question of whether this is the result of a
      loss of function of PrPC in copper transport across the plasma membrane at the
      synapse, we have used synaptosomes incubated with 67Cu as a model system to
      characterize the mechanism of copper accumulation in nerve terminals. Our results
      demonstrate that mouse brain synaptosomes accumulate copper efficiently by at
      least two distinct mechanisms. In the presence of 1 mM EDTA, copper was taken up
      via a saturable high-affinity process that was moderately susceptible to
      competition by high concentrations of NiCl2. Uptake characteristics were clearly
      different in the presence of 400 microM histidine, with the most noticeable
      dissimilarities being considerably elevated uptake rates and moderate competition
      by ZnCl2 rather than NiCl2. No significant differences in copper uptake
      capability between WT and PrPC-knockout synaptosomes were observed under any of
      the experimental conditions tested in this study. Furthermore, preincubation of
      synaptosomes with an antibody binding to the copper-binding repeat region of the
      prion protein had no effect on copper uptake either. Taken together, our data
      indicate that synaptosomal copper uptake is independent of PrPC.

PMID- 16280604
TI  - Impairment of long-term potentiation in the CA1, but not dentate gyrus, of the
      hippocampus in Obese Zucker rats: role of calcineurin and phosphorylated CaMKII.
AB  - Obese Zucker rat (OZR) is a genetic model of obesity with noninsulin-dependent
      diabetes and hypertension. The OZR exhibit hyperinsulinemia, hyperlipidmia, and
      high circulating glucocorticoid levels. We have shown previously that long-term
      potentiation (LTP) is impaired in the CA1 region of the hippocampus of OZR. In
      the present work, although electrophysiological recording from anesthetized OZR
      hippocampus showed impaired LTP in the CA1, an intact LTP was recorded in the
      dentate gyrus (DG) region of the hippocampus of the same OZR. Thus, LTP is
      differentially impaired in the CA1 compared with the DG region of OZR
      hippocampus. Immunoblotting was used to investigate the molecular mechanism
      responsible for impairment of LTP in the CA1 but not in the DG region. Analysis
      revealed reduction in the levels of phosphorylated calcium-dependent calmodulin
      kinase II (P-CaMKII) and total CaMKII in the CA1 region of OZR. However, in the
      DG region, reduction was observed only in the levels of total CaMKII, with no
      change in P-CaMKII levels. The ratio of P-CaMKII to total CaMKII was increased in
      the DG but not in the CA1 area of hippocampus of OZR. Although unchanged in the
      CA1, calcineurin levels were significantly reduced in the DG of OZR. These
      findings suggest that the DG might possess a compensatory mechanism whereby
      calcineurin levels are reduced to allow sufficient P-CaMKII to produce an
      apparently normal LTP in the DG area of OZR hippocampus.

PMID- 16280608
TI  - Letter to the editor: outbreaks caused by parvovirus B19.

PMID- 16280609
TI  - Pneumococcal vaccination policy in Europe.
AB  - Infection due to Streptococcus pneumoniae (Pneumococcus) (Pnc) is an important
      cause of invasive clinical manifestations such as meningitis, septicaemia and
      pneumonia, particularly in young children and the elderly. A 23-valent
      polysaccharide Pnc vaccine (PPV) has been available for many years and a 7-valent
      conjugate Pnc vaccine (PCV) has been licensed since 2001 in Europe. As part of a
      European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a
      questionnaire was distributed to all 15 EU member states, Switzerland, Norway and
      the 10 accession countries in 2003 to ascertain current pneumococcal vaccination
      policy. Twenty three of the 27 target countries, constituting the current
      European Union (plus Norway and Switzerland), completed the questionnaire. PPV
      was licensed in 22 of the 23 responding countries and was in the official
      recommendations of 21. In all the 20/21 countries for which information was
      available, risk groups at higher risk of infection were targeted. The number of
      risk groups targeted ranged from one to 12. At least 17 countries recommend that
      PPV be administered to all those >65 years of age (in three countries, to those
      over 60 years of age). Thirteen countries had developed national recommendations
      for PCV in 2003. No country recommended mass infant immunisation at that time,
      but rather targeted specific risk groups (between 1 and 11), particularly
      children with asplenia (n=13) and HIV infection (n=12). PCV use was restricted to
      children under two years of age in seven countries, and in four countries to
      children under five years of age. Future decisions on use of pneumococcal
      vaccines in Europe will be decided on the basis of several factors including:
      local disease burden; the predicted impact of any universal programme,
      particularly the importance of serotype replacement and herd immunity (indirect
      protection to the unvaccinated population); the effectiveness of reduced dose
      schedules, and vaccine cost. Indeed, at least one country, Luxembourg, has since
      implemented a universal infant PCV immunisation policy.

PMID- 16280610
TI  - The epidemiology of severe Streptococcus pyogenes associated disease in Europe.
AB  - Several European countries reported outbreaks of severe disease caused by
      Streptococcus pyogenes in the late 1980s. This marked a departure from the
      previous decades, where very few such outbreaks were noted. These changes in
      disease occurrence formed part of a global phenomenon, the reasons for which have
      yet to be explained. Results of surveillance activities for invasive S. pyogenes
      infection within Europe over the past fifteen years identified further increases
      in many countries. However, variations in surveillance methods between countries
      preclude robust comparisons being made, illustrating the need for a unified
      surveillance strategy across Europe. This was finally embodied in the Strep-EURO
      programme, introduced in 2002.

PMID- 16280611
TI  - Outbreak of tinea corporis gladiatorum, a fungal skin infection due to
      Trichophyton tonsurans, in a French high level judo team.
AB  - An outbreak of 49 cases of tinea corporis gladiatorum due to Trichophyton
      tonsurans infection occurred in a high level judo team of 131 members in Orleans,
      central France, between October 2004 and April 2005. The team was divided into 5
      groups: cadet-junior boys (n=44), cadet-junior girls (n=33), male university
      students (n= 15), female university students (n=21), and a group called 'pole
      technique' made up of high level judokas who have finished academic study (n=18).
      The outbreak involved 86% of the cadet-junior boys, but only 6 men in the 'pole
      technique' (33%) and only 5 of the 69 other team members (7%) (cadet-junior girls
      and university students). We describe the outbreak and the results of a survey
      that found a known risk factor for the 'pole technique': sharing an electric hair
      shaver. Personal hygiene practices were found to be very good among the cadet
      junior boys. The high attack rate in this group may be linked to the poor shower
      facilities in the gymnasium where they practiced that led them to have their
      showers several hours after the end of daily practice.

PMID- 16280612
TI  - Wound botulism in injectors of drugs: upsurge in cases in England during 2004.
AB  - Wound infections due to Clostridium botulinum were not recognised in the UK and
      Republic of Ireland before 2000. C. botulinum produces a potent neurotoxin which
      can cause paralysis and death. In 2000 and 2001, ten cases were clinically
      recognised, with a further 23 in 2002, 15 in 2003 and 40 cases in 2004. All cases
      occurred in heroin injectors. Seventy cases occurred in England; the remainder
      occurred in Scotland (12 cases), Wales (2 cases) and the Republic of Ireland (4
      cases). Overall, 40 (45%) of the 88 cases were laboratory confirmed by the
      detection of botulinum neurotoxin in serum, or by the isolation of C. botulinum
      from wounds. Of the 40 cases in 2004, 36 occurred in England, and of the 12 that
      were laboratory confirmed, 10 were due to type A. There was some geographical
      clustering of the cases during 2004, with most cases occurring in London and in
      the Yorkshire and Humberside region of northeast England.

PMID- 16280613
TI  - Real or media-mediated outbreak of coxsackie infections in 2002 in Greece?
AB  - The purpose of this study was to provide evidence about the existence of a
      coxsackie B outbreak in Greece in 2002 by comparing data of laboratory confirmed
      coxsackie B recent infections in northern Greece between 1998-2001 with data from
      2002. The infections were confirmed serologically, using the indirect
      immunofluorescence method detecting IgM antibodies for coxsackie B1-B6 viruses.
      Sera from 2701 patients residents of northern Greece who were suspected to be
      suffering from coxsackie B virus infections were examined: 2056 between 1998 and
      2001, and 645 in 2002. The comparison between the results of laboratory confirmed
      cases and data available at the laboratory between the two periods showed that:
      The total number of patients examined per year was higher in 2002 (645 versus an
      annual average of 514 in 1998-2001). The proportion of laboratory confirmed
      recent infections was lower in 2002 (27.8% versus 32.7%) and the estimated
      incidence was 0.66/10,000 for 2002 and 0.32-0.84/10,000 for 1998-2001. The age
      distribution differed: the proportions of cases in children versus cases in
      adults were reversed in 2002 compared with 1998-2001, with a higher proportion
      among children in 2002. The difference between the two periods was statistically
      significant. Children aged 3-5 years were the age group most affected in 2002.
      Seasonal distribution remained the same for both periods (peaks in spring and
      autumn). In 2002, three fatal cases occurred in April, but no deaths were
      reported in 1998-2001. The clinical syndromes involved also differed: cases of
      respiratory infections, mainly pneumonia, rose from 5.75% to 24.3% in children in
      2002 and cases of myopericarditis rose in adults from 13% in 1998-2001 to 29.5%
      in 2002. The last finding, combined with the involvement of the media (because of
      the three fatal cases) and the panic in the general public that followed
      suggested that an outbreak had occurred, but we conclude that there was no
      outbreak.

PMID- 16280614
TI  - An outbreak of mumps in Sweden, February-April 2004.
AB  - Between 24 February and 26 April 2004, Vastra Gotaland county in Sweden reported
      42 cases of suspected mumps. A descriptive study of the cases was undertaken. A
      questionnaire was administered by telephone and vaccine effectiveness was
      calculated using the screening method. Seventy four per cent (31/42) of the
      suspected cases were interviewed by telephone. Eight out of the 42 serum samples
      were positive or equivocal for mumps IgM by ELISA. Mumps virus genome was
      identified in 21/42 (50%) saliva samples. Eleven were selected for sequencing and
      all were confirmed to be mumps virus. Cases were predominantly from 2 small
      towns. Eighteen out of 19 cases that developed bilateral swelling could be linked
      to one small town. The median age of interviewed cases was 43 years (range 5 to
      88). Six cases were admitted to hospital, 5 of which were older than 30 years.
      The highest incidence occurred in the 35 to 44 years age group. Vaccine
      effectiveness was estimated to be 65% for 1 dose and 91% for 2 doses. This
      descriptive study shows the increasing age of mumps cases with increasing vaccine
      coverage. Vaccine effectiveness was particularly high for 2 doses. Second-dose
      uptake must be ensured, as primary vaccine failure is well documented in mumps.
      Stronger precautions must be taken to avoid pools of susceptible older
      individuals accumulating due to the increased risk of complications.

PMID- 16280615
TI  - Navigation and analysis of the energy landscape of small proteins using the
      activation-relaxation technique.
AB  - The resolution of the protein folding problem has been tied to the development of
      a detailed understanding of the configurational energy or of the free energy
      landscape associated with these molecules. Using the activation-relaxation
      technique and a simplified energy model, we present here a detailed analysis of
      the energy landscape of 16-residue peptide that folds into a beta-hairpin. Our
      results support the concept of an energy landscape with an effective topology
      consistent with a scale-free network.

PMID- 16280616
TI  - A methodology for efficiently sampling the conformation space of molecular
      structures.
AB  - Motivated by recently developed computational techniques for studying protein
      flexibility, and their potential applications in docking, we propose an efficient
      method for sampling the conformational space of complex molecular structures. We
      focus on the loop closure problem, identified in the work of Thorpe and Lei (2004
      Phil. Mag. 84 1323-31) as a primary bottleneck in the fast simulation of
      molecular motions. By modeling a molecular structure as a branching robot, we use
      an intuitive method in which the robot holds onto itself for maintaining loop
      constraints. New conformations are generated by applying random external forces,
      while internal, attractive forces pull the loops closed. Our implementation,
      tested on several model molecules with low number of degrees of freedom but many
      interconnected loops, gives promising results that show an almost four times
      speed-up on the benchmark cube-molecule of Thorpe and Lei.

PMID- 16280617
TI  - Counting out to the flexibility of molecules.
AB  - We outline the mathematical models, and the related counting algorithms, that are
      the basis for fast computations to predict biomolecular flexibility and rigidity.
      Within these mathematical models, we describe the snap-shot flexibility
      (instantaneous motions) of biomolecules, extracted from a single snap-shot of the
      molecule and the connection to larger finite motions. We illustrate the results
      and techniques with direct analysis of simple secondary structures. Understanding
      these basic ideas clarifies both the limits and the power of the algorithms, as
      well as the prospects for extensions and refinements of these algorithms.

PMID- 16280618
TI  - Constrained geometric simulation of diffusive motion in proteins.
AB  - We describe a new computational method, FRODA (framework rigidity optimized
      dynamic algorithm), for exploring the internal mobility of proteins. The rigid
      regions in the protein are first determined, and then replaced by ghost templates
      which are used to guide the movements of the atoms in the protein. Using random
      moves, the available conformational phase space of a 100 residue protein can be
      well explored in approximately 10-100 min of computer time using a single
      processor. All of the covalent, hydrophobic and hydrogen bond constraints are
      maintained, and van der Waals overlaps are avoided, throughout the simulation. We
      illustrate the results of a FRODA simulation on barnase, and show that good
      agreement is obtained with nuclear magnetic resonance experiments. We
      additionally show how FRODA can be used to find a pathway from one conformation
      to another. This directed dynamics is illustrated with the protein dihydrofolate
      reductase.

PMID- 16280619
TI  - Protein flexibility using constraints from molecular dynamics simulations.
AB  - Proteins are held together in the native state by hydrophobic interactions,
      hydrogen bonds and interactions with the surrounding water, whose strength as
      well as spatial and temporal distribution affects protein flexibility and hence
      function. We study these effects using 10 ns molecular dynamics simulations of
      pure water and of two proteins, the glutamate receptor ligand binding domain and
      barnase. We find that most of the noncovalent interactions flicker on and off
      over typically nanoseconds, and so we can obtain good statistics from the
      molecular dynamics simulations. Based on this information, a topological network
      of rigid bonds corresponding to a protein structure with covalent and noncovalent
      bonds is constructed, with account being taken of the influence of the flickering
      hydrogen bonds. We define the duty cycle for the noncovalent interactions as the
      percentage of time a given interaction is present, which we use as an input to
      investigate flexibility/rigidity patterns, in the algorithm FIRST which
      constructs and analyses topological networks.

PMID- 16280620
TI  - Protein folding by motion planning.
AB  - We investigate a novel approach for studying protein folding that has evolved
      from robotics motion planning techniques called probabilistic roadmap methods
      (PRMs). Our focus is to study issues related to the folding process, such as the
      formation of secondary and tertiary structures, assuming we know the native fold.
      A feature of our PRM-based framework is that the large sets of folding pathways
      in the roadmaps it produces, in just a few hours on a desktop PC, provide global
      information about the protein's energy landscape. This is an advantage over other
      simulation methods such as molecular dynamics or Monte Carlo methods which
      require more computation and produce only a single trajectory in each run. In our
      initial studies, we obtained encouraging results for several small proteins. In
      this paper, we investigate more sophisticated techniques for analyzing the
      folding pathways in our roadmaps. In addition to more formally revalidating our
      previous results, we present a case study showing that our technique captures
      known folding differences between the structurally similar proteins G and L.

PMID- 16280621
TI  - Combinatorial docking approach for structure prediction of large proteins and
      multi-molecular assemblies.
AB  - Protein folding and protein binding are similar processes. In both, structural
      units combinatorially associate with each other. In the case of folding, we
      mostly handle relatively small units, building blocks or domains, that are
      covalently linked. In the case of multi-molecular binding, the subunits are
      relatively large and are associated only by non-covalent bonds. Experimentally,
      the difficulty in the determination of the structures of such large assemblies
      increases with the complex size and the number of components it contains.
      Computationally, the prediction of the structures of multi-molecular complexes
      has largely not been addressed, probably owing to the magnitude of the
      combinatorial complexity of the problem. Current docking algorithms mostly target
      prediction of pairwise interactions. Here our goal is to predict the structures
      of multi-unit associations, whether these are chain-connected as in protein
      folding, or separate disjoint molecules in the assemblies. We assume that the
      structures of the single units are known, either through experimental
      determination or modeling. Our aim is to combinatorially assemble these units to
      predict their structure. To address this problem we have developed CombDock.
      CombDock is a combinatorial docking algorithm for the structural units assembly
      problem. Below, we briefly describe the algorithm and present examples of its
      various applications to folding and to multi-molecular assemblies. To test the
      robustness of the algorithm, we use inaccurate models of the structural units,
      derived either from crystal structures of unbound molecules or from modeling of
      the target sequences. The algorithm has been able to predict near-native
      arrangements of the input structural units in almost all of the cases, suggesting
      that a combinatorial approach can overcome the imperfect shape complementarity
      caused by the inaccuracy of the models. In addition, we further show that through
      a combinatorial docking strategy it is possible to enhance the predictions of
      pairwise interactions involved in a multi-molecular assembly.

PMID- 16280623
TI  - Elastic network models for understanding biomolecular machinery: from enzymes to
      supramolecular assemblies.
AB  - With advances in structure genomics, it is now recognized that knowledge of
      structure alone is insufficient to understand and control the mechanisms of
      biomolecular function. Additional information in the form of dynamics is needed.
      As demonstrated in a large number of studies, the machinery of proteins and their
      complexes can be understood to a good approximation by adopting Gaussian (or
      elastic) network models (GNM) for simplified normal mode analyses. While this
      approximation lacks chemical details, it provides us with a means for assessing
      the collective motions of large structures/assemblies and perform a comparative
      analysis of a series of proteins, thus providing insights into the mechanical
      aspects of biomolecular dynamics. In this paper, we discuss recent applications
      of GNM to a series of enzymes as well as large structures such as the HK97
      bacteriophage viral capsids. Understanding the dynamics of large protein
      structures can be computationally challenging. To this end, we introduce a new
      approach for building a hierarchical, reduced rank representation of the protein
      topology and consequently the fluctuation dynamics.

PMID- 16280622
TI  - Structural transitions in Cowpea chlorotic mottle virus (CCMV).
AB  - Viral capsids act as molecular containers for the encapsulation of genomic
      nucleic acid. These protein cages can also be used as constrained reaction
      vessels for packaging and entrapment of synthetic cargos. The icosahedral Cowpea
      chlorotic mottle virus (CCMV) is an excellent model for understanding the
      encapsulation and packaging of both genomic and synthetic materials. High
      resolution structural information of the CCMV capsid has been invaluable for
      evaluating structure-function relationships in the assembled capsid but does not
      allow insight into the capsid dynamics. The dynamic nature of the CCMV capsid
      might play an important role in the biological function of the virus. The CCMV
      capsid undergoes a pH and metal ion dependent reversible structural transition
      where 60 separate pores in the capsid open or close, exposing the interior of the
      protein cage to the bulk medium. In addition, the highly basic N-terminal domain
      of the capsid, which is disordered in the crystal structure, plays a significant
      role in packaging the viral cargo. Interestingly, in limited proteolysis and mass
      spectrometry experiments the N-terminal domain is the first part of the subunit
      to be cleaved, confirming its dynamic nature. Based on our fundamental
      understanding of the capsid dynamics in CCMV, we have utilized these aspects to
      direct packaging of a range of synthetic materials including drugs and inorganic
      nanoparticles.

PMID- 16280624
TI  - Solvation and desolvation effects in protein folding: native flexibility, kinetic
      cooperativity and enthalpic barriers under isostability conditions.
AB  - As different parts of a protein chain approach one another during folding, they
      are expected to encounter desolvation barriers before optimal packing is
      achieved. This impediment originates from the water molecule's finite size, which
      entails a net energetic cost for water exclusion when the formation of
      compensating close intraprotein contacts is not yet complete. Based on recent
      advances, we extend our exploration of these microscopic elementary desolvation
      barriers' roles in the emergence of generic properties of protein folding. Using
      continuum Go-like C(alpha) chain models of chymotrypsin inhibitor 2 (CI2) and
      barnase as examples, we underscore that elementary desolvation barriers between a
      protein's constituent groups can significantly reduce native conformational
      fluctuations relative to model predictions that neglected these barriers. An
      increasing height of elementary desolvation barriers leads to thermodynamically
      more cooperative folding/unfolding transitions (i.e., higher overall empirical
      folding barriers) and higher degrees of kinetic cooperativity as manifested by
      more linear rate-stability relationships under constant temperature. Applying a
      spatially non-uniform thermodynamic parametrization we recently introduced for
      the pairwise C(alpha) potentials of mean force, the present barnase model further
      illustrates that desolvation is a probable physical underpinning for the
      experimentally observed high intrinsic enthalpic folding barrier under
      isostability conditions.

PMID- 16280625
TI  - Energy landscapes and properties of biomolecules.
AB  - Thermodynamic and dynamic properties of biomolecules can be calculated using a
      coarse-grained approach based upon sampling stationary points of the underlying
      potential energy surface. The superposition approximation provides an overall
      partition function as a sum of contributions from the local minima, and hence
      functions such as internal energy, entropy, free energy and the heat capacity. To
      obtain rates we must also sample transition states that link the local minima,
      and the discrete path sampling method provides a systematic means to achieve this
      goal. A coarse-grained picture is also helpful in locating the global minimum
      using the basin-hopping approach. Here we can exploit a fictitious dynamics
      between the basins of attraction of local minima, since the objective is to find
      the lowest minimum, rather than to reproduce the thermodynamics or dynamics.

PMID- 16280627
TI  - Singing and evil in visual art.
AB  - Surprisingly, singing and music sometimes are connected with poor or even lethal
      outcomes. One example is personified in the legend of Orpheus, who through the
      power of his songs, succeeded in leading the wild Thracians into the Greek
      religion. This did not save him, however, from being murdered by Thracian women
      probably because of his paedophilic tendency. The scene has been illustrated
      since 490 BC on Attic red-figure vases. The Sirens, with the body of a bird and
      the head of a female and dwelling in the Sicilian Sea, were creatures who
      attracted sailors by their song and devoured the unhappy wretches who had been
      unable to resist their seductive singing. This topic has also been depicted on
      ancient Greek vases as part of the Odyssey. The idea that beautiful singing with
      an instrument can also be a symbol of sin and a sign of the devil is deeply
      rooted in Christian thinking. This aspect of music as the power of evil is
      extensively depicted in Dutch and Flemish genre paintings where singing and
      playing string instruments were also common symbols of lust and vices, seduction
      and, therefore, moral decay. Some examples of the power of evil in singing in
      representative art are presented in this article.

PMID- 16280626
TI  - Computational architecture of the yeast regulatory network.
AB  - The topology of regulatory networks contains clues to their overall design
      principles and evolutionary history. We find that while in- and out-degrees of a
      given protein in the regulatory network are not correlated with each other, there
      exists a strong negative correlation between the out-degree of a regulatory
      protein and in-degrees of its targets. Such correlation positions large
      regulatory modules on the periphery of the network and makes them rather well
      separated from each other. We also address the question of relative importance of
      different classes of proteins quantified by the lethality of null-mutants lacking
      one of them as well as by the level of their evolutionary conservation. It was
      found that in the yeast regulatory network highly connected proteins are in fact
      less important than their low-connected counterparts.

PMID- 16280628
TI  - Breath management: gender-based differences in classical singers.
AB  - Fifty-five subjects (38 female, 17 male), consisting of professional operatic
      singers, singing teachers and advanced classical voice students, were surveyed to
      explore gender-based differences in breath management strategies for singing.
      Respondents evaluated extent and significance of thoracic and abdominal movement
      for inhalation and for control of singing extended phrases. Females were found to
      concentrate breath efforts lower in the body than did men (hypogastric vs.
      epigastric regions). Both groups relied heavily on low thoracic activity to
      provide an antagonistic mechanism for control. Results corroborated a review of
      standard pedagogical literature, which showed variations in recommended breathing
      methods that strongly correlate to the gender of the author.

PMID- 16280629
TI  - Muscular patterns and activation levels of auxiliary breathing muscles and thorax
      movement in classical singing.
AB  - The aim of this paper is to present an overview of the findings in seven studies
      exploring muscular patterns and muscle activation levels in selected muscles by
      classical singers. In addition, the relationship of these muscles to thorax (TX)
      movement was investigated. Loading levels and respiratory phasing of upper
      trapezius (TR), sternocleidomastoideus (STM) and the scalenes (SC) were
      investigated in vocalization tasks with variation in vocal loudness and pitch.
      Further, muscle activity in the posterior neck (PN) was investigated in
      inhalation and phonation and, finally, TR, intercostal (INT), lateral abdominal
      (OBL) and anterior abdominal (RC) muscle loading in student and professional
      singers was examined. Muscle activity was recorded by use of an ambulatory four
      channel monitoring system (Physiometer PHY 400, Premed, Norway). TX movement was
      traced with two strain gauge sensors (RES-117) placed around the upper TX and
      lower TX. A phasing of upper TR activity to INT and OBL activity was discovered,
      all muscles supporting the expiration phase. During phonation, TR contributes in
      the compression of the upper TX, thus serving as an accessory muscle of
      expiration. TR activity is reduced with short breathing cycles and is mostly
      inactive in simplified speaking tasks. During phonation, professional opera
      singers activate the expiratory-phased TR, INT, OBL and RC muscles to higher
      levels than student singers do. STM and SC show correlated activity patterns
      during inhalation and phonation by classical singers. During demanding singing,
      expiratory-phased STM and SC activity peaks produce a counterforce to the
      compression of upper TX at high pitches. As breathing demands are lowered, STM
      and SC activity are reduced and attain inspiratory phasing. Substantial muscle
      activity is observed in PN during inhalation and phonation. EMG biofeedback
      performed on TR and STM have a secondary effect of lowering EMG activity in PN.

PMID- 16280630
TI  - 'Mixing' the registers: glottal source or vocal tract?
AB  - Electroglottograph and microphone signals are examined of scale passages crossing
      the boundary between chest and middle registers in the female singing voice. From
      a protocol executed by professional classical singers, the examples are selected
      to illustrate differing approaches to the chest-middle transition, as well as to
      illuminate varying theories on the female middle register, specifically the
      question of 'mixing' the primary registers, chest and falsetto. The results
      suggest that the skillful tuning of the resonances of the vocal tract contributes
      more toward the pedagogical goal of smoothing the register transition than does a
      presumed mixing of the registers at the glottal source.

PMID- 16280631
TI  - Resonance strategies revealed in recorded tenor high notes.
AB  - With careers that depend to a large extent on the amplitude and sonorous beauty
      of their voices, opera singers must pay special attention to high notes, where
      the wide spacing of the harmonics of the voice source intensifies the critical
      importance of the tuning of the resonances of the vocal tract. This study uses
      spectrum analysis to examine a large number of recordings of a particularly
      challenging high note for tenors, the final sustained B4-flat of the aria
      'Celeste Aida' from Verdi's opera Aida. The resonance strategy most frequently
      found uses a markedly displaced second formant to create a dominant resonance at
      the frequency of the third harmonic, about 1,400 Hz. Other strategies and
      combinations of strategies are examined as well. Arguments concerning the
      validity of drawing conclusions from the acoustic signals available in commercial
      recordings are considered, and it is concluded that such recordings can contain
      valuable information on resonance strategies for those who aspire to sing similar
      high notes.

PMID- 16280632
TI  - The interplay between glottis and vocal tract during the male passaggio.
AB  - The transition between 'chest' and 'head' register is essential for male opera
      singers in order to reach the higher pitches. The 'passaggio', which is a scale
      passage where this transition takes place, but also a maneuver of register
      equalization, is typically difficult to learn. Studies on parameters for a
      definition of this transition are restricted to a small number of singers so far.
      Audio, electroglottographic, and equivalent subglottic pressure signals of 11
      male opera singers were recorded while singing scales on open back vowels and
      passing the register transition. A spectrum analysis of the audio signal revealed
      that the second harmonic (H2) dominates in 'chest', resonated by the first
      formant (F1), together with the fourth harmonic (H4), supported by the second
      formant (F2). During the passaggio, H2 level decreases because it loses the
      resonance of F1, while the third harmonic (H3) gains the resonance of F2. At this
      point the H4 level drops because that harmonic is no longer supported by F2. The
      transition from 'chest' to 'head' register is marked by characteristic changes in
      the amplitude patterns of the partials H2, H3, and H4, and the frequency
      progressions of the first two formants, defining an objective distinction between
      the two registers.

PMID- 16280633
TI  - Serotonin transporter function is an early step in left-right patterning in chick
      and frog embryos.
AB  - The neurotransmitter serotonin has been shown to regulate a number of embryonic
      patterning events in addition to its crucial role in the nervous system. Here, we
      examine the role of two serotonin transporters, the plasma membrane serotonin
      transporter (SERT) and the vesicular monoamine transporter (VMAT), in embryonic
      left-right asymmetry. Pharmacological or genetic inhibitors of either SERT or
      VMAT specifically randomized the laterality of the heart and viscera in Xenopus
      embryos. This effect takes place during cleavage stages, and is upstream of the
      left-sided gene XNR-1. Targeted microinjection of an SERT-dominant negative
      construct confirmed the necessity for SERT function in embryonic laterality and
      revealed that the descendants of the right ventral blastomere are the most
      dependent upon SERT signaling in left-right patterning. Moreover, the importance
      of SERT and VMAT in laterality is conserved in chick embryos, being upstream of
      the early left-sided gene Shh. Endogenous transcripts of SERT and VMAT are
      expressed from the initiation of the primitive streak in chick and are
      asymmetrically expressed in Hensen's node. Taken together our data characterize
      two new right-sided markers in chick gastrulation, identify a novel, early
      component of the left-right pathway in two vertebrate species, and reveal a new
      biological role for serotonin transport.

PMID- 16280634
TI  - Gliogenic radial glial cells show heterogeneity in the developing mouse spinal
      cord.
AB  - The central nervous system of the mammalian embryo is organized according to the
      expression of region-specific transcription factors along the anteroposterior
      and/or the dorsoventral axis. For example, the dorsal ventricular zone (VZ) of
      the embryonic spinal cord expresses Pax3 and Pax7, the ventral VZ expresses Pax6,
      and the more ventral VZ expresses Nkx2.2. Properties of neuronal precursors
      located in the VZ are determined by the characteristic expression patterns of
      these transcription factors, leading to the generation of distinct classes of
      neurons. Recent studies demonstrated that radial glial cells produce neurons in
      addition to glia during central nervous system development. Thus, neuronal
      precursor diversity may be dependent upon the diversity of radial glial cells. To
      investigate this hypothesis, we analyzed the expression of radial glial cell
      markers and transcription factors in the mouse embryonic spinal cord. We show
      that radial glial cells indeed express domain-specific transcription factor.
      Moreover, they varied in expression of the astrocyte-specific glutamate
      transporter. The region where the astrocyte-specific glutamate transporter is
      strongly expressed in the ventral radial glial cells is closely related to the
      Pax6-expressing domain, and the weakly expressing region corresponding to the
      Nkx2.2-expressing domain. Furthermore, dorsal radial fibers expressed ephrin-B1.
      Thus, different types of radial glial cells exist in different domains defined by
      the transcription factor expression at E12.5. We also show that this diversity
      continues to the gliogenic stage of radial glial cells. This raises the idea that
      astrocytes generated from different domains along the dorsoventral axis in the
      mouse spinal cord have distinct characteristics.

PMID- 16280635
TI  - Immunohistochemical and microarray analyses of a mouse model for the smith-lemli
      opitz syndrome.
AB  - The Smith-Lemli-Opitz syndrome is a mental retardation/malformation syndrome with
      behavioral components of autism. It is caused by a deficiency in 3beta
      hydroxysteroid-Delta7-reductase (DHCR7), the enzyme required for the terminal
      enzymatic step of cholesterol biosynthesis. The availability of Smith-Lemli-Opitz
      syndrome mouse models has made it possible to investigate the genesis of the
      malformations associated with this syndrome. Dhcr7 gene modification (Dhcr7-/-)
      results in neonatal lethality and multiple organ system malformations. Pathology
      includes cleft palate, pulmonary hypoplasia, cyanosis, impaired cortical response
      to glutamate, and hypermorphic development of hindbrain serotonergic neurons. For
      the current study, hindbrain regions microdissected from gestational day 14 Dhcr7
      /-, Dhcr7+/- and Dhcr7+/+ fetuses were processed for expression profiling
      analyses using Affymetrix oligonucleotide arrays and filtered using statistical
      significance (S-score) of change in gene expression. Of the 12,000 genes
      analyzed, 91 were upregulated and 98 were downregulated in the Dhcr7-/-
      hindbrains when compared to wild-type animals. Fewer affected genes, representing
      a reduced affect on these pathways, were identified in heterozygous animals.
      Hierarchical clustering identified altered expression of genes associated with
      cholesterol homeostasis, cell cycle control and apoptosis, neurodifferentiation
      and embryogenesis, transcription and translation, cellular transport,
      neurodegeneration, and neuronal cytoskeleton. Of particular interest, Dhcr7 gene
      modification elicited dynamic changes in genes involved in axonal guidance. In
      support of the microarray findings, immunohistochemical analyses of the
      netrin/deleted in colorectal cancer axon guidance pathway illustrated midline
      commissural deficiencies and hippocampal pathfinding errors in Dhcr7-/- mice. The
      results of these studies aid in providing insight into the genesis of human
      cholesterol-related birth defects and neurodevelopmental disorders and highlight
      specific areas for future investigation.

PMID- 16280636
TI  - Involvement of the ubiquitin-mediated proteolytic system in the signaling pathway
      induced by ceramide in primary astrocyte cultures.
AB  - The selective degradation of abnormal or short half-life proteins in eukaryotic
      cells proceeds through the ubiquitin-mediated proteolytic system (UbPS). The
      signals that tag the proteins for their ubiquitination are well known. In the
      present study, our aim was to investigate the relationship between the action of
      ceramide and the changes in the expression of certain mRNAs of the Ub pathway and
      in the activation of the UbPS in cultured astrocytes (ASTs). Changes in the
      expression of components that are known to be substrates of the UbPS and that
      participate in the regulation of the cell death process were also studied.
      Addition of different concentrations of C2 ceramide to cultured ASTs produced an
      increase in the expression of the Ub gene and in the gene that encodes E1, one of
      the enzymes involved in the ubiquitination process, without any changes on cell
      viability. Immunocytochemical studies showed an increase in the expression of Bcl
      2 with no changes in cytochrome c. Also, there was an increase in the nuclear
      reactivity of NFkappaB, suggesting a translocation of this factor towards the
      nucleus. Western blots showed a decrease in IkappaB and its phosphorylated form
      as well as an increase in Bcl-2 with no changes in cytochrome c. All of these
      compounds appear to be acting as possible modulators of AST responses to C2
      ceramide. Our results suggest that in AST primary cultures, C2 ceramide, at the
      concentrations used in this study, does not produce apoptosis. However, it
      induces an activation of the UbPS, probably as a consequence of an activation of
      phosphatases and kinases, or through the generation of reactive oxygen species,
      which act as triggering signals of the UbPS. The fundamental role of NFkappaB and
      Bcl-2 as antiapoptotic factors is discussed.

PMID- 16280638
TI  - An opportunity to distance the FDA from Washington politics.

PMID- 16280637
TI  - Matrix metalloproteinases and their inhibitors in the developing mouse brain and
      spinal cord: a reverse transcription quantitative polymerase chain reaction
      study.
AB  - Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are essential for
      coordinated extracellular matrix turnover during central nervous system
      development. Reverse transcription quantitative polymerase chain reaction was
      employed to evaluate the mRNA expression of MMP-2, -3, -7, -9, -10, -11, -12, 
      13, -14, -15, and -24, and TIMP-1, -2, -3, and -4 in the prosencephalon,
      rhombencephalon, and spinal cord of 1- to 40-week-old mice. The molecular data
      were interpreted in the context of morphological observations. Significantly
      higher expression levels of MMP-2, -11, -13, -14, -15, and -24, and TIMP-1 and -3
      were found in the brain and spinal cord 1 week after birth compared to later time
      points, while MMP-9 and TIMP-2 upregulation was restricted to the brain. This
      upregulation coincided with the maximal extension of the transient cerebellar
      external granular layer, a marker of neuronal progenitor proliferation and
      migration. MMP-12 was significantly upregulated at later time points and found to
      be positively correlated with myelination in the rhombencephalon and spinal cord.
      MMP-3, -7, and -10 mRNA expressions remained unchanged or were negligible. In
      summary, while most of the MMPs and TIMPs studied seem to be involved in cell
      proliferation and migration, MMP-12 might be decisive for myelination.

PMID- 16280639
TI  - Advances in diabetes research: from cell biology to cell therapy. Proceedings of
      the Fourth Annual Rachmiel Levine Diabetes and Obesity Symposium. November 4-8,
      2003. Universal City, California, USA.

PMID- 16280640
TI  - The Fourth Annual Rachmiel Levine Symposium: introduction.

PMID- 16280641
TI  - Immunotherapeutic approaches to prevent, ameliorate, and cure type 1 diabetes.
AB  - Type 1A diabetes (T1D) is caused by autoimmune islet beta cell destruction
      precipitated by environmental triggers in genetically predisposed individuals.
      Islet beta cells produce insulin and are the primary target of this autoimmune
      disorder. Insulin, glutamic acid decarboxylase, and insulinoma associated-2
      autoantibodies (IAA, GAD65, and IA-2) are the autoantibodies that have been
      associated most clearly with the development of T1D. Despite our current ability
      to predict T1D using genetic markers and detecting islet autoantibodies, we have
      yet to find a safe way to prevent the disease. However, there are more than 100
      different therapies that prevent T1D in the nonobese diabetic (NOD) mouse model
      or the BioBreeding (BB) rats. This paper reviews a few select therapeutic
      approaches that have been or are being evaluated as possibilities for the
      prevention, amelioration, or cure of T1D.

PMID- 16280642
TI  - Genetic and genomic studies of the BTBR ob/ob mouse model of type 2 diabetes.
AB  - The BTBR mouse strain harbors alleles promoting insulin resistance. When made
      genetically obese (ob/ob), these mice develop severe type 2 diabetes (fasting
      glucose >400 mg/dL). By contrast, C57BL/6 ob/ob mice are able to compensate for
      the obesity-induced insulin resistance by increasing pancreatic insulin secretion
      and thus maintain only slightly elevated plasma glucose levels (<250 mg/dL).
      Islet insulin secretory responses to glucose are undiminished in the remaining
      islets of BTBR ob/ob mice. A genome-wide linkage analysis identified 3 major loci
      influencing plasma glucose and/or insulin levels in an F2ob/ob sample derived
      from the 2 strains. A locus on chromosome 2 affects insulin sensitivity and is
      independent of obesity. Loci on chromosomes 16 and 19 affect fasting glucose and
      insulin levels and likely affect beta-cell mass or function. Analysis of mRNA
      expression patterns revealed a reduction in lipogenic gene expression in adipose
      tissue associated with obesity. Conversely, hepatic lipogenic gene expression
      increases in obese mice, but to a much greater extent in the diabetes-resistant
      C57BL/6 strain. We propose that hepatic lipogenic capacity affects susceptibility
      to obesity-induced diabetes.

PMID- 16280643
TI  - Role of nitric oxide in diabetic complications.
AB  - Diabetic vascular disease is accompanied by decreased formation of the
      vasodilators, nitric oxide (NO), and prostacyclin and increased formation of
      vasoconstrictor eicosanoids, which exacerbate the progression of vascular
      disease. Similarities between the dysfunction introduced by short-term effects of
      elevated glucose and long-term effects of diabetes suggest that the alteration in
      endothelial factors in diabetes primarily results from exposure of endothelial
      cells to elevated glucose, although undoubtedly hyperlipidemia contributes as
      well. A key alteration in endothelial cell phenotype is increased formation of
      reactive oxygen species. This is in part due to uncoupling of endothelial NO
      synthase such that it generates superoxide anion in addition to NO. This is
      responsible for NO synthase to produce peroxynitrite, a damaging molecule.
      Peroxynitrite inactivates prostacyclin synthase leading to the accumulation of
      inflammatory and prothrombotic eicosanoids. This not only helps to explain the
      impairment of endothelial vasodilator mechanisms, but also increased progression
      of vascular disease. Many of these cellular abnormalities can be prevented by
      adequate scavenging of oxygen-derived free radicals or by blocking the actions of
      the eicosanoids at thromboxane (TP) receptors. Exposure to elevated glucose also
      gives rise to oxidants in smooth muscle, and recent studies indicate that
      oxidation of cysteine thiols under these conditions may prevent physiological NO
      signaling. As a result, the responsiveness to NO is impaired and accounts in part
      for abnormal endothelium-dependent vasodilation.

PMID- 16280645
TI  - Gene therapy for type 1 diabetes.
AB  - The most intensively studied autoimmune disorder, type 1 diabetes mellitus (DM1),
      has attracted perhaps the greatest interest for gene-based therapeutic and
      prophylactic interventions. The final clinical manifestation of this
      immunologically and genetically complex disease, the absence of insulin, is the
      major starting point for almost all the gene therapy modalities attempted to
      date. Insulin replacement by transplantation of islets of Langerhans or surrogate
      beta cells is the obvious choice, but the allogeneic nature of the transplants
      activates potent antidonor immunoreactivity necessitating gene and cell-based
      immunosuppressive strategies as an alternative to the toxic pharmacologic
      immunosuppressives indicated for classic solid organ transplants. Accumulating
      knowledge of the cellular mechanisms involved in onset, however, have yielded
      promising tolerance induction prophylactic approaches using genes and cells.
      Despite the early successes in a number of animal models, the true test of
      efficacy in humans remains to be demonstrated.

PMID- 16280644
TI  - Integrating genetic and gene expression data to study the metabolic syndrome and
      diabetes in mice.
AB  - Increasingly, the mouse is becoming the standard model for mammalian physiology
      and disease. It can be genetically analyzed and manipulated with relative ease.
      Moreover, the endogenous genetic variation that exists among inbred mouse strains
      can be exploited to identify genetic control of complex physiologic processes
      involved in diabetes and the metabolic syndrome, among other conditions relevant
      to human disease. Recent advances in genetics and gene expression technology have
      greatly increased the knowledge to be derived from this approach when applied to
      traditional genetic studies.

PMID- 16280646
TI  - Oxidative stress and pancreatic beta-cell dysfunction.
AB  - Oxidative stress is induced under diabetic conditions through various pathways,
      including the electron transport chain in mitochondria and the nonenzymatic
      glycosylation reaction, and is likely involved in progression of pancreatic beta
      cell dysfunction developing in diabetes. beta-Cells are vulnerable to oxidative
      stress, possibly due to low levels of antioxidant enzyme expression. When
      oxidative stress was induced in vitro in beta cells, the insulin gene promoter
      activity and mRNA levels were suppressed, accompanied by the reduced activity of
      pancreatic and duodenal homeobox factor-1 (PDX-1) (also known as IDX-1/STF
      1/IPF1), an important transcription factor for the insulin gene. The suppression
      of oxidative stress by a potent antioxidant, N-acetyl-l-cysteine or probucol, led
      to the recovery of insulin biosynthesis and PDX-1 expression in nuclei and
      improved glucose tolerance in animal models for type 2 diabetes. As a possible
      cause of this, we recently found that PDX-1 was translocated from the nucleus to
      the cytoplasm in response to oxidative stress. Furthermore, the addition of a
      dominant-negative form of c-Jun N-terminal kinase (JNK) inhibited the oxidative
      stress-induced PDX-1 translocation, suggesting an essential role of JNK in
      mediating the phenomenon. Taken together, the oxidative stress-mediated
      activation of the JNK pathway leads to nucleocytoplasmic translocation of PDX-1
      and thus is likely involved in the progression of beta-cell dysfunction found in
      diabetes.

PMID- 16280648
TI  - The recent finding that tissue factor is produced by the pancreatic islets
      constitutes a possible link between insulin resistance and cardiovascular
      disease.
AB  - Approximately 70% of the patients admitted to the hospital with an acute
      myocardial infarction have type 2 diabetes mellitus or impaired glucose tolerance
      (IGT). Insulin resistance with compensatory hyperinsulinemia is a feature that is
      common to both type 2 diabetes and IGT. Increased risk of coronary heart disease
      (CHD) in conditions characterized by insulin resistance has been associated with
      hyperinsulinemia and hyperproinsulinemia. As indicated in several studies, there
      exists a connection between postprandial hyperinsulinemia/hyperglycemia and
      activation of the coagulation cascade. The recent finding that tissue factor (TF)
      is produced and secreted by the alpha and beta cells of the islets of Langerhans
      maybe the link between these 2 conditions. The local production of TF in human
      islets and excretion of microparticle-bound or alternatively spliced soluble TF
      in response to prolonged periods of hyperglycemia provide a tentative explanation
      for the activation of the TF pathway during hyperinsulinemia. Here we review the
      field and set forth a hypothesis that links TF expression in the islets of
      Langerhans to the increased risk of CHD.

PMID- 16280650
TI  - Advanced glycation end products and diabetic nephropathy.
AB  - Chronic hyperglycemia and oxidative stress in diabetes results in the formation
      and accumulation advanced glycation end products (AGEs). AGEs have a wide range
      of chemical, cellular, and tissue effects that contribute to the development of
      microvascular complications. In particular, AGEs appear to have a key role in the
      diabetic nephropathy. Their importance as downstream mediators of tissue injury
      in diabetic kidney disease is demonstrated by animal studies using inhibitors of
      advanced glycation to retard the development of nephropathy without directly
      influencing glycemic control. AGE modification of proteins may produce in changes
      charge, solubility, and conformation leading to molecular dysfunction as well as
      disrupting interactions with other proteins. AGEs also interact with specific
      receptors and binding proteins to influence the renal expression of growth
      factors and cytokines, implicated in the progression of diabetic renal disease.
      The effects of AGEs appears to be synergistic with other pathogenic pathways in
      diabetes including oxidative stress, hypertension, and activation of the renin
      angiotensin system. Each of these pathways may be activated by AGEs, and each may
      promote the formation of AGEs in the vicious cycle associated with progressive
      renal damage. It is likely that therapies that inhibit the formation of AGEs or
      remove established AGE modifications will form an important component part of
      future therapy in patients with diabetes, acting in concert with conventional
      approaches to prevent diabetic renal injury.

PMID- 16280649
TI  - Genetic basis of diabetic nephropathy.
AB  - Diabetes mellitus is the leading cause of end-stage renal disease. Development
      and progression of diabetic nephropathy result from a combination of genetic
      susceptibility and metabolic and hemodynamic abnormalities. In America, some
      racial and ethnic minorities have a significant burden of diabetic nephropathy,
      and, although genetic studies suggest that inherited factors play a major role in
      the pathogenesis of diabetic nephropathy, little information has been gained on
      the genes and molecular mechanisms involved. The genetic background of diabetic
      nephropathy is believed to be polygenic, and the genes predisposing to the
      development and progression of diabetic nephropathy are actively being
      investigated. New knowledge in identifying and understanding the role of
      susceptibility gene(s) will provide valuable information that could help develop
      new preventive and therapeutic strategies.

PMID- 16280651
TI  - T-cell assays to determine disease activity and clinical efficacy of immune
      therapy in type 1 diabetes.
AB  - Type 1 (insulin-dependent) diabetes mellitus results from a T cell-mediated
      autoimmune destruction of the pancreatic beta cells in genetically predisposed
      individuals. Therapies directed against T cells have been demonstrated to halt
      the disease process and prevent recurrent beta-cell destruction after islet
      transplantation. Less is known about the nature and function of these T cells,
      the cause of the loss of tolerance to islet autoantigens, why the immune system
      apparently fails to suppress autoreactivity, and whether (or which)
      autoantigen(s) are critically involved in the initiation or progression of
      disease. Autoreactive T cells have proven to be valuable targets to study
      pathogenic or diabetes-related processes. Measuring T-cell autoreactivity also
      provided critical information to determine the fate of islet allografts
      transplanted to type 1 diabetic patients. Furthermore, these studies have
      provided proof of operational immunologic tolerance to islet allografts as well
      as valuable information to improve and customize immunosuppressive therapy.
      Currently, technologies to detect T-cell auto- and alloreactivity in type 1
      diabetic recipients of islet allografts are applied to monitor islet allograft
      survival in relation with various immunosuppressive therapies and to guide
      tapering of these therapies after successful restoration of insulin production.
      Although it is generally appreciated that studies on cellular auto- and
      alloimmunity are hampered by the complex nature of such immune responses and the
      required technical and physical skills, it has been a worthwhile quest to unravel
      the role of T cells in the pathogenesis of type 1 diabetes and islet allograft
      destruction.

PMID- 16280647
TI  - Targeting T lymphocytes for immune monitoring and intervention in autoimmune
      diabetes.
AB  - Recognition of a peptide-MHC complex by the T cell receptor (TCR) is a key
      interaction that initiates T lymphocyte activation or silencing during an immune
      response. Fluorochrome-labeled recombinant MHC class II-peptide reagents function
      as soluble mimetics of this interaction, bind to their specific TCR, and allow
      for detection of antigen-specific CD4+ T cells. These reagents are now under
      scrutiny for "immune staging" of patients at risk of type 1 diabetes, in an
      effort to diagnose islet autoimmunity early enough to block immune-mediated beta
      cell destruction. Several issues are currently being addressed to improve the
      performance of these T cell assays: enrichment steps for better sensitivity,
      multiplexing of several islet epitopes, simultaneous monitoring of CD4+ and CD8+
      responses, detection of low avidity T cells, combination of quantitative (number
      of positive cells) and qualitative (cytokine secretion, naive/memory phenotype)
      readouts. CD4+ T cells are key effectors of autoimmunity, and these MHC class II
      peptide reagents, through their signaling properties, might also provide
      therapeutics to block the autoimmune process at its onset, analogous to the use
      of OKT3gammao1(AlaAla) anti-CD3 antibody but in an antigen-specific fashion. The
      aim of such therapeutics is to potentiate different physiological control
      mechanisms to restore immune tolerance. Mechanisms initiated by this pathway may
      be capable of triggering elimination of pathogenic T cells through antigen
      specific apoptosis and anergy, combined with the induction of regulatory T cells
      with broad suppressive function.

PMID- 16280652
TI  - Autoimmune destruction of pancreatic beta cells.
AB  - Type 1 diabetes results from the destruction of insulin-producing pancreatic beta
      cells by a beta cell-specific autoimmune process. Beta cell autoantigens,
      macrophages, dendritic cells, B lymphocytes, and T lymphocytes have been shown to
      be involved in the pathogenesis of autoimmune diabetes. Beta cell autoantigens
      are thought to be released from beta cells by cellular turnover or damage and are
      processed and presented to T helper cells by antigen-presenting cells.
      Macrophages and dendritic cells are the first cell types to infiltrate the
      pancreatic islets. Naive CD4+ T cells that circulate in the blood and lymphoid
      organs, including the pancreatic lymph nodes, may recognize major
      histocompatibility complex and beta cell peptides presented by dendritic cells
      and macrophages in the islets. These CD4+ T cells can be activated by interleukin
      (IL)-12 released from macrophages and dendritic cells. While this process takes
      place, beta cell antigen-specific CD8+ T cells are activated by IL-2 produced by
      the activated TH1 CD4+ T cells, differentiate into cytotoxic T cells and are
      recruited into the pancreatic islets. These activated TH1 CD4+ T cells and CD8+
      cytotoxic T cells are involved in the destruction of beta cells. In addition,
      beta cells can also be damaged by granzymes and perforin released from CD8+
      cytotoxic T cells and by soluble mediators such as cytokines and reactive oxygen
      molecules released from activated macrophages in the islets. Thus, activated
      macrophages, TH1 CD4+ T cells, and beta cell-cytotoxic CD8+ T cells act
      synergistically to destroy beta cells, resulting in autoimmune type 1 diabetes.

PMID- 16280654
TI  - Update on regulatory issues in pancreatic islet transplantation.
AB  - Over the past 12 years, the US Food and Drug Administration (FDA) has reviewed
      more than 40 investigational new drug applications for the use of allogeneic
      pancreatic islets to treat type 1 diabetes mellitus. Recent advances in islet
      cell isolation, transplantation, and immunosuppressive maintenance have led to
      multiple centers reporting promising results in the treatment of type 1 diabetes
      with allogeneic islet cells. The FDA held an advisory committee meeting on
      October 9-10, 2003, to explore the potential for licensing allogeneic islets as a
      therapy for severe type 1 diabetes. This article highlights the manufacturing
      challenges, discussed by the FDA advisory committee, that remain to be resolved
      before allogeneic islets can be approved for treatment of type 1 diabetes. This
      article also briefly addresses the challenges facing the clinical trial design of
      studies that could be used to support licensure.

PMID- 16280653
TI  - Peptide-mediated immunosuppression.
AB  - There is now a substantial body of data demonstrating the abilities of synthetic
      peptides and peptide analogues to inhibit the auto- and alloimmune response in
      vitro and in vivo. We have studied the immunomodulatory role of synthetic
      peptides derived from highly conserved regions of the class II MHC alpha chain.
      These MHC-derived peptides inhibit the rat, human, and mouse mixed lymphocyte
      response (MLR), proliferation to autoantigen, cytokine production, and cytolytic
      T lymphocyte (CTL) generation. Our studies demonstrated that the inhibitory
      effect of the MHC class II nonpolymorphic peptides is mediated through the
      induction of apoptosis in APCs via a nonclassic caspase-independent pathway. In
      addition, T lymphocytes initially stimulated in the presence of HLA-DQA1 are
      rendered hyporesponsive to subsequent stimuli. Immunomodulation by HLA-DQA1 was
      effective in vivo because it prevented both the priming and the effector function
      of primed allogeneic T cells in a murine DTH model. Our data demonstrate that
      peptides derived from highly conserved regions of the class II MHC alpha chain
      can alter T-lymphocyte immune responses both in vitro and in vivo. These results
      have important implications for the development of a novel therapy for immune
      mediated diseases.

PMID- 16280655
TI  - Evaluation of erectile dysfunction therapy in patients previously nonadherent to
      long-term medications: a retrospective analysis of prescription claims.
AB  - Erectile dysfunction (ED) can lead to treatment noncompliance in patients taking
      medications for chronic health conditions. Using the Intelligent Health
      Repository, NDCHealth's longitudinal, United States health care claims database,
      we examined the impact of treating ED on adherence to long-term therapies in
      previously nonadherent patients. Male patients >or=18 years of age were
      identified who received antidepressant (AD), antihypertensive (AH), oral
      hypoglycemic (OHG), or lipid-lowering (LL) agents and initiated therapy with
      sildenafil citrate (Viagra) between January and June 2003. Treatment adherence
      was determined using medication possession ratios (MPRs) for the 12 months before
      and after the first prescription of sildenafil. Prior to initiation of therapy
      for ED with sildenafil, 64% of patients with comorbid medications were not
      adherent (MPR <0.8). Among these patients, 728 (27%) received AD, 2112 (78%)
      received AH, 984 (18%) received OHG, and 1078 (40%) received LL agents, with 66%
      of patients receiving multiple therapeutic classes. During the 12-month period
      after the first sildenafil prescription, patients had a significant increase in
      medication adherence compared with the 12 months before the first prescription of
      sildenafil (P < 0.0001). The percentage of patients who became adherent (MPR
      >or=0.8) with medications after sildenafil treatment was from 22% to 36%. With
      the exception of the LL group, there was a significant relationship between >or=3
      sildenafil prescriptions and change in MPR (P < 0.05). Patients aged >or=65 years
      had similar improvement in MPR as patients <or=65 years. Treatment of ED with
      sildenafil improved adherence in patients taking common long-term medications who
      were previously nonadherent.

PMID- 16280656
TI  - Safety of zinc gluconate glycine (Cold-Eeze) in a geriatric population: a
      randomized, placebo-controlled, double-blind trial.
AB  - Zinc gluconate glycine lozenges are an over-the-counter homeopathic remedy that
      significantly reduced the duration and severity of common colds in adults in 2
      independent clinical trials. To evaluate the safety of zinc gluconate glycine
      lozenges in elderly individuals with 1 or more health conditions, with or without
      a cold. This randomized, double-blind, placebo-controlled, parallel-group trial
      enrolled men and women between 60 and 91 years of age, who self-administered 1
      zinc gluconate glycine or placebo lozenge every 3 to 4 hours for 6 days. One or
      more of the following conditions was present in the study population: arthritis,
      cancer, depression, heart disease, hypertension, lung disease, osteoporosis,
      prostate disease, and stroke. Assessments were performed at baseline and at 7 (+/
      1 day) and 14 days. The safety evaluation considered physical examinations,
      clinical laboratory tests, vital signs, adverse events, and concomitant
      medications. Of 75 persons enrolled, 66 completed the study. Safety assessments
      demonstrated no clinically significant differences between treatment groups. Four
      participants taking zinc tablets and 3 participants taking placebo tablets
      reported mild adverse events. Of those participants taking zinc tablets, 6
      adverse events were possibly related to the study product and 2 adverse events
      were probably related to the study product. Of those participants taking placebo
      tablets, 3 adverse events were reported that were possibly related to the study
      product. No serious or clinically significant adverse events were noted. Zinc
      gluconate glycine lozenges are safe and well tolerated by a geriatric population
      and are suitable for prophylactic or therapeutic use to reduce the duration or
      severity of the common cold.

PMID- 16280657
TI  - Follicular dendritic cell immunohistochemical markers in angioimmunoblastic T
      cell lymphoma.
AB  - Angioimmunoblastic T-cell lymphoma is characterized by a paracortical
      proliferation of medium to large neoplastic T cells, often with clear cytoplasm,
      in a background of arborizing high endothelial venules, many surrounded by
      follicular dendritic cells (FDCs). IHC staining may be applied to highlight these
      extrafollicular FDCs, traditionally using CD21, or CD23. Several alternative FDC
      markers have been described, including CNA.42, cystatin A/acid cysteine
      proteinase inhibitor (ACPI, involved in antigen presentation), and fascin (an
      actin binding protein). The authors stained a collection of 45 angioimmunoblastic
      T-cell lymphomas with CD21, CD23, CNA.42, cystatin A, and fascin for direct
      comparison of FDC staining characteristics in this setting. CD21 highlighted the
      expected dendritic network of cell processes, within residual follicles and
      outside of follicles, often adjacent to proliferating vessels. CD23 exhibited
      similar staining quality but was less sensitive than CD21. CNA.42 showed only
      diffuse weak labeling of FDCs. Cystatin A stained the cytoplasm of follicular
      dendritic cells within and outside of follicles; however, staining was often not
      sharply localized to dendritic cell processes, and scoring was further
      complicated by reactivity with other cell types in over half of the cases.
      Likewise, fascin stained a variety of cell types, including strong staining of
      interdigitating dendritic-like cells, moderate staining of endothelial cells, and
      only weak staining of follicular dendritic cells within and outside of follicles.
      Thus, CD21 remains the most reliable marker of follicular dendritic cells in
      angioimmunoblastic T-cell lymphoma.

PMID- 16280658
TI  - Utility of syndecan-1 (CD138) expression in the diagnosis of undifferentiated
      malignant neoplasms: a tissue microarray study of 1,754 cases.
AB  - Syndecan-1, a heparan sulfate-rich membrane glycoprotein, is expressed in plasma
      cells and is considered a reliable marker of plasmacytic differentiation.
      However, it has not been widely tested in non-hematolymphoid tissues, and thus
      its utility in the setting of an undifferentiated malignant neoplasm has not been
      evaluated. The authors conducted an extensive study of CD138 staining in over
      1,700 normal, benign, and malignant non-hematolymphoid tissues, using five tissue
      microarrays. Immunohistochemical staining was performed with two commercially
      available CD138 monoclonal antibodies directed against syndecan-1 (Serotec,
      Oxford, UK, and DAKO, Carpenteria, CA). In addition to the specific membrane
      staining, many normal tissues and epithelial tumors showed strong cytoplasmic
      immunoreactivity. A small subset of mesenchymal neoplasms also showed membrane
      and cytoplasmic immunoreactivity. In squamous cell carcinoma of the head and
      neck, renal cell carcinoma, and prostate adenocarcinoma, the intensity of CD138
      staining inversely correlated with the histologic grade of the carcinoma.
      However, statistically significant staining differences and their correlation
      with histologic grades differed depending on whether the Serotec or the DAKO
      antibody was used. These results indicate that CD138 immunoreactivity is
      widespread in normal and neoplastic epithelial tissues, as well as a variety of
      undifferentiated epithelial and mesenchymal processes. The authors conclude that
      the expression of syndecan-1, although relatively specific to plasma cells within
      the hematolymphoid system, should be interpreted with extreme caution in the
      setting of an undifferentiated neoplasm. Furthermore, the two commercially
      available monoclonal CD138 antibodies tested in this study showed significant
      differences in their immunoreactivity in different tumor types.

PMID- 16280659
TI  - CD5-positive B-cell neoplasms of indeterminate immunophenotype: a
      clinicopathologic analysis of 26 cases.
AB  - The flow cytometric classification of CD5-positive small B-cell neoplasms is
      dependent largely on the differential expression of CD23 and FMC-7. Occasional
      CD5-positive neoplasms with prominent co-expression of these antigens are
      encountered, precluding definitive immunophenotypic classification. The authors
      studied the clinicopathologic features of 26 neoplasms with this indeterminate
      immunophenotype. Available morphologic material was reviewed and analysis of
      CYCLIN D1 derangement was performed in selected cases by a combination of
      immunohistochemical, molecular, and cytogenetic techniques. Individual neoplasms
      were classified based on correlation of morphologic features and results of
      CYCLIN D1 studies. The neoplasms were classified into five categories: chronic
      lymphocytic leukemia (14 cases), "favor chronic lymphocytic leukemia" (3 cases),
      mantle cell lymphoma (3 cases), lymphoplasmacytic lymphoma (1 case), and
      unclassifiable (5 cases). Three of the unclassifiable neoplasms had morphologic
      features of mantle cell lymphoma, but CYCLIN D1 derangement could not be
      demonstrated. Neither relative expression of CD23 and FMC-7 nor intensity of CD20
      or surface immunoglobulin expression was helpful in final classification. The
      authors conclude that CD5-positive small B-cell neoplasms with an indeterminate
      immunophenotype are a heterogeneous group, requiring additional studies for final
      classification. The majority (65%) appear to be chronic lymphocytic leukemia,
      with most of the remaining cases either definitively mantle cell lymphoma or
      unclassifiable.

PMID- 16280660
TI  - SP4, a novel anti-cyclin D1 rabbit monoclonal antibody, is a highly sensitive
      probe for identifying mantle cell lymphomas bearing the t(11;14)(q13;q32)
      translocation.
AB  - Immunohistochemistry is the most widely used approach in the diagnosis of mantle
      cell lymphoma (MCL). However, its reliability may be hampered by several
      technical reasons, necessitating the use of alternative techniques such as the
      identification of the t(11;14)(q13;q32) translocation to characterize such
      lesions. The authors compared two monoclonal antibodies (DCS-6 and SP4) for
      assessing cyclin D1 immunoreactivity in a series of 22 MCLs. Their results
      documented that SP4, a novel rabbit monoclonal antibody, is more effective than
      the mouse monoclonal antibody DCS-6, one of the most commonly used reagents in
      daily practice. Although DCS-6 and SP4 were capable of identifying cyclin D1
      immunoreactivity in 95.4% and 100% of the cases analyzed, respectively, the
      prevalence of cyclin D1 immunoreactive neoplastic cells was significantly (P <
      0.0001) higher with SP4 (86.6 +/- 13.1%) than with DCS-6 (39.8 +/- 32%).
      Moreover, the staining intensity was faint in 16 (76.2%) cases and moderate to
      strong in 5 (23.8%) cases immunostained with DCS- 6, while all the cases showed a
      moderate to strong immunoreactivity with SP4 (P < 0.0001). According to an
      arbitrary score based on the percentage of immunoreactive neoplastic cells and
      staining intensity, only 10 (45.4%) cases were considered high cyclin D1
      expressors after staining with DCS-6, whereas all the cases were high expressors
      with SP4 (P < 0.0001). These data provide evidence that the SP4 monoclonal
      antibody may be a fast, easy-to-interpret, and reliable surrogate for the
      detection of the (11;14) translocation by molecular techniques.

PMID- 16280661
TI  - Distribution and ZAP-70 expression of WHO lymphoma categories in Shanxi, China: a
      review of 447 cases using a tissue microarray technique.
AB  - This study aims to assess the distribution of lymphoma subtypes in Shanxi, China,
      according to the World Health Organization (WHO) classification, and to compare
      the relative distribution with other areas of the world. H&E-stained tissue
      sections from the archives of the Shanxi Tumor Hospital, China, were reviewed and
      447 cases with sufficient materials were selected for detailed study. A panel of
      antibodies and probes was assembled, including antibodies to ALK1, bcl-6, CDs
      1alpha, 3, 4, 5, 7, 8, 10, 15, 20, 23, 30, 43, 56, 68, 79alpha, and 99, cyclin
      D1, EMA, kappa, lambda, LMP1, PAX5, TdT, Vs38C and ZAP70, plus EBER RNA probe by
      in situ hybridization. The 447 lymphoma cases, subtyped according to the WHO
      classification, were assembled in triplicate into 11 tissue microarrays and
      examined with the panel of markers described. Among the 447 cases, 385 (82.6%)
      were confirmed to be non-Hodgkin lymphomas (NHL) and 62 (13.9%) were Hodgkin
      lymphomas of classic type (CHL). Of the NHL cases, 68.6% were B-cell lymphomas
      and 30.6% T/NK-cell lymphomas. Histiocytic neoplasms accounted for only three
      cases (0.8%). Diffuse large B-cell lymphomas (DLBCL) were the most common subtype
      (35.1%), followed by peripheral T-cell lymphomas unspecified (PTun, 12.0%),
      extranodal marginal zone B-cell lymphomas (MALT lymphomas, 11.7%), follicular
      lymphomas (FL, 8.6%), T-lymphoblastic lymphomas (T-LBL, 7.0%), anaplastic large
      cell lymphomas (ALCL, 4.2%), B small lymphocytic lymphomas (B SLL, 3.6%), and
      mantle cell lymphomas (MCL, 2.6%). Of 263 B-cell neoplasms, 105 (39.9%) expressed
      immunoglobulin light chain, including 52 kappa and 53 lambda, detectable in
      paraffin sections. The incidence of DLBCL was similar to many Western countries
      and Asia. The frequency of FL was, however, much lower than the usual pattern in
      Western countries, although NK/T-cell lymphomas were more common (30.6%), similar
      to other countries in Asia, including Japan and Korea. With regard to markers of
      EBV infection, 8 of 385 (2.1%) NHL cases gave positive findings by both in situ
      hybridization (EBER RNA) and immunohistochemistry (LMP-1), whereas 24 (6.2%)
      expressed only the EBER and 12 (3.1%) expressed only LMP-1. EBV positivity was
      found in 24 of 119 (20.2%) T and NK cell lymphomas, in 20 of 263 (7.6%) B cell
      neoplasms, and in 37 of 62 (59.7%) CHLs. In CHLs there was complete concordance
      of results by both in situ hybridization (EBER RNA) and immunohistochemistry (LMP
      1) procedures. ZAP70 was detected in most T cell-lineage disorders (61.4%) and
      also in a subset of B small lymphocytic lymphomas (50%). However, ZAP-70 was
      expressed in a minority of other types of B-cell lymphomas, including precursor B
      cell acute lymphoblastic leukemia (25%), diffuse large B-cell lymphoma (26.7%),
      follicular lymphoma (15.2%), and lymphoplasmacytic lymphoma (9.1%).
      Immunohistochemical analysis represents an effective method for assessing ZAP-70
      expression and reveals that a variety of B-cell malignant neoplasms express ZAP
      70, albeit at low frequency.

PMID- 16280662
TI  - Correlation of HER2 gene amplification with immunohistochemistry in breast cancer
      as determined by a novel monoplex polymerase chain reaction assay.
AB  - Amplification of the HER2 oncogene in breast cancer identifies patients who are
      likely to respond to anti-HER2 mAb therapy. Current clinical practice dictates
      that all breast cancers first undergo HER2 screening by IHC. Strongly positive
      (3+ on a 0-to-3+ scale) IHC cases are considered as HER2-amplified tumors and are
      not evaluated further because of the strong correlation between HER2 gene
      amplification as measured by FISH and 3+ IHC. This strong correlation has
      recently been questioned, and some data suggest that over 50% of 3+ IHC HER2
      immunostains may not be due to HER2 gene amplification. To help resolve this
      discrepancy, the authors developed a quantitative PCR assay for HER2.
      Quantitative PCR was used to determine the amount of HER2 DNA relative to a
      control gene, IF2 (eukaryotic translation initiation factor, 2p11.1-q11.1). The
      PCR assay is performed on genomic DNA isolated from paraffin-embedded breast
      cancer tissue. The PCR assay developed is a monoplex assay in which the HER2 and
      IF2 PCRs are performed in separate cuvettes. Cases of HER2 FISH amplified breast
      cancer and HER2 FISH nonamplified breast cancer were chosen for study by monoplex
      HER2 PCR. HER2 overexpression was evaluated by IHC. Twenty-two cases of HER2
      positive and 22 cases of HER2-negative breast cancer, as determined by FISH, were
      assayed for HER2 by PCR and IHC. Sixteen of the 44 cases were interpreted as 3+
      IHC. All 16 showed HER2 amplification by PCR and 15 showed HER2 amplification by
      FISH. One FISH negative case was found to be HER2 amplified by PCR and showed 3+
      IHC stain, suggesting the FISH result in this case was underinterpreted. Two FISH
      positive cases were found to be negative by PCR and negative in IHC as well,
      suggesting the FISH result in these cases was overinterpreted. The authors
      conclude that 3+ IHC membrane staining correctly identifies neoplasms showing
      HER2 gene amplification. Monoplex HER2 PCR may offer significant advantages over
      both IHC and FISH for HER2 testing in breast cancer.

PMID- 16280663
TI  - Potential diagnostic utility of CDX-2 immunophenotyping in extramammary Paget's
      disease.
AB  - Extramammary Paget's disease (EMPD) is a rare condition whose importance is
      amplified by its association with either cutaneous or internal malignancy.
      Recently it has been shown that EMPD is not a single disease but can be divided
      into cutaneous and endodermal subtypes. The authors studied 12 new cases of
      immunohistochemically well-characterized EMPD, including HER-2/neu and CDX-2
      immunophenotyping. The latter represents a novel application of this nuclear
      transcription factor, considered to be a relatively specific IHC marker for
      gastrointestinal-type epithelium. Cutaneous EMPD, accounting for 10 of the 12
      (83%) cases, was CDX2-/HER2+; endodermal EMPD, accounting for 2 of the 12 (17%)
      cases, was CDX2+/HER2-. Four of the 12 cases (33%) were associated with a
      malignancy (two cutaneous adenocarcinomas, two colorectal carcinomas). The two
      cases of cutaneous adenocarcinoma occurred in the cutaneous group (2/10 [20%]),
      while the two cases of rectal carcinoma (one invasive, one in situ) occurred in
      the endodermal group (2/2 [100%]). Since EMPD subtypes have specific implications
      with regard to cancer risk, immunophenotyping should be performed in all cases.
      CDX-2 immunoreactivity may be useful in the subtyping of EMPD.

PMID- 16280664
TI  - Differential immunoprofiles of hepatocellular carcinoma, renal cell carcinoma,
      and adrenocortical carcinoma: a systemic immunohistochemical survey using tissue
      array technique.
AB  - The differential diagnoses of hepatocellular carcinoma (HCC), renal cell
      carcinoma (RCC), and adrenocortical carcinoma (ACC) are sometimes difficult due
      to their overlapping histologic features. Immunohistochemistry is a helpful
      adjunct in supporting the histologic diagnosis. In this study, the authors used
      the tissue array technique to systemically analyze the efficacy of different
      immunohistochemical panels in discerning these neoplasms. Immunohistochemical
      stains were performed on a total of 895 tumors (including 170 HCCs, 176 RCCs, and
      40 ACCs) using monoclonal antibodies against hepatocyte antigen (HPA), CD10, RCC
      marker, vimentin, alpha-inhibin, keratins (KL-1, CAM 5.2, 7, and 20), epithelial
      membrane antigen, and polyclonal antibodies against carcinoembryonic antigen
      (pCEA) and alpha-fetoprotein, and antibodies Melan-A (A103), MOC31, and BG8. HPA
      immunostain alone detected 85.9% of HCCs, and the addition of canalicular pattern
      of pCEA and CD10 immunostains raised the sensitivity to 94.7%. RCC marker was
      positive in 54.5% of RCCs but was negative in all non-RCC tumors. Using positive
      CD10 and negative HPA and pCEA together with RCC marker increased the sensitivity
      to 74.4%. Immunoreactivity for alpha-inhibin and A103 could be detected in 67.5%
      and 55% of ACCs, respectively. When the two antibodies were combined, 82.5% of
      ACCs were labeled. Proper selection of immunohistochemical stains aid in the
      differential diagnosis of the three neoplasms. Using the tissue array technique,
      the authors also showed an effective model for comprehensive antibody testing.

PMID- 16280665
TI  - Regenerative hyperplasia of follicular epithelium in chronic lymphocytic
      thyroiditis.
AB  - The thyroid gland is an endocrine organ composed of stable cells. It is well
      known that regenerative capacity of the thyroid tissue is minimal. Various
      degrees of morphologic alterations do occur in chronic lymphocytic thyroiditis
      (CLT), including Hashimoto's thyroiditis. Eighty-five CLT cases were analyzed for
      these morphologic alterations. Small, irregular, atrophic or hyperplastic thyroid
      follicles were seen adjacent to the lymphocytic infiltration. There was nuclear
      enlargement, loss of nuclear polarity in thyrocytes and intrafollicular thyrocyte
      proliferation in these follicles. We thought that the morphologic alterations in
      involved follicles could be due to regenerative hyperplasia with increased
      proliferative activity and basement membrane abnormalities. To examine this
      hypothesis we investigated Ki-67 and laminin immunoreactivity in the involved
      follicles adjacent to lymphocytic infiltration areas. The uninvolved follicles
      were used as controls. Immunopositivity of Ki-67 in involved follicles was
      significantly higher than that in uninvolved follicles (2.97% +/- 2.16 versus
      0.83% +/- 1.63, P < 0.001). Laminin immunostaining indicated the destruction or
      irregular distribution of basement membrane in involved follicles. We conclude
      that the increased cell proliferation activity and basement membrane
      abnormalities in the follicles with morphologic changes adjacent to CLT occur in
      conjunction with regenerative hyperplasia.

PMID- 16280666
TI  - Immunohistochemistry in the differential diagnosis between primary and secondary
      intestinal adenocarcinoma of the urinary bladder.
AB  - Distinguishing between primary adenocarcinomas and secondary colonic
      adenocarcinomas of the urinary bladder is often difficult because they appear
      morphologically similar but invariably require different treatment strategies.
      The aim of the study was to define the utility of a limited immunohistochemical
      panel consisting of CDX-2, cytokeratins 7 (CK7) and 20 (CK20), and
      carcinoembryonic antigen (CEA) in differentiating primary from secondary bladder
      adenocarcinomas. Formalin-fixed, paraffin-embedded tissues from 8 primary bladder
      adenocarcinomas and 23 colorectal adenocarcinomas involving the bladder were
      included in the study. Statistical analysis was performed using the Fisher exact
      test. The majority (87.5%) of primary bladder adenocarcinomas were CDX-2
      negative, and only one case of primary bladder adenocarcinoma was positive, while
      CDX-2 was strongly expressed in the nucleus of all cases of secondary (colonic)
      bladder tumor (P < 0.0005). Five cases (62.5%) of primary bladder adenocarcinoma
      and one case (4.3%) of secondary bladder tumor showed positive staining for CK7
      (P = 0.002), whereas CK20 showed positive staining in five cases (62.5%) of
      primary bladder adenocarcinoma and in all the secondary bladder tumors (P =
      0.012). All 23 secondary bladder tumors and 7 primary bladder adenocarcinomas
      (87.5%) expressed CEA (P = 0.25). These data demonstrate that a restricted
      immunohistochemical panel consisting of CDX-2, CK7, CK20, and CEA may be of use
      in differentiating primary bladder adenocarcinoma from secondary adenocarcinoma
      of colorectal origin.

PMID- 16280667
TI  - Immunohistochemical detection of NRSA on small cell lung cancer with a monoclonal
      antibody (MAG-1) that recognizes the carboxyl terminus of provasopressin.
AB  - A single monoclonal antibody (MAG-1) directed against the C-terminal 18-amino
      acid region (VAGc18) of provasopressin was examined as an agent for recognizing
      the tumor-specific NRSA marker common to small cell lung cancer (SCLC) in
      formalin-fixed tissues with ABC immunohistochemistry. SCLC tumors were obtained
      from several tissue locations and included primary, metastatic, and recurrent
      disease. Positive staining was found in 91% of cases (53/58). All five of the
      unreactive tumors were of the lungs or chest wall, and there did not appear to be
      an association of this negativity with disease stage, age, or sex. Alternatively,
      almost all primary lesions, almost all metastatic lesions, and all recurrent
      lesions examined gave a positive reaction with MAG-1. For this study, vasopressin
      producing cells of the human anterior hypothalamus served as a positive control,
      while negative controls comprised normal lung tissue, tumor that received MAG-1
      in the presence of an excess of antigen (VAGc18 peptide), or tumor reacted with a
      commercial IgG1 isotype as primary antibody. All of the results indicate that MAG
      1 can be effectively used to selectively identify the NRSA marker on almost all
      SCLC tumors, at all disease stages, and at all locations. Since all four tumors
      tested showing no reactivity with MAG-1 gave a positive reaction for
      synaptophysin, it is proposed that a combined use of MAG-1 with synaptophysin
      antibodies could allow all SCLC tumors to be detected by ABC
      immunohistochemistry.

PMID- 16280668
TI  - eIF4E as a marker for cervical neoplasia.
AB  - Eukaryotic translation initiation factor 4E (eIF4E) is upregulated in cancers of
      the breast and head and neck. The authors have shown that eIF4E is increased in
      cervical neoplasia and that eIF4E upregulates human papillomavirus (HPV)
      oncoprotein E7. The aim of this study was to quantitate eIF4E in tissues
      representing a wide range of cervical pathology. The potential correlation
      between dysplastic grade or tumor stage with eIF4E upregulation and/or HPV
      genotype was analyzed for 10 normal, 27 cancer, and 37 dysplasia cases. A
      progressive increase in eIF4E staining intensity was found with increasing
      cervical pathology (P < 0.0001). No difference was seen in eIF4E stain intensity
      by either tumor type--squamous cell cancer (n = 18), adenocarcinoma (n = 4), or
      other types of cancer (n = 5) (P = 0.97)--or by tumor grade--II (n = 5) versus
      III (n = 7). Likewise, neither an HPV typing result of HPV 16 (n = 10) versus non
      HPV 16 (n = 4) nor single HPV infection (n = 11) versus dual HPV infection (n =
      3) significantly altered the eIF4E stain results (P = 0.86 and 0.97,
      respectively). These results indicate that eIF4E stain intensity may be useful as
      a marker for cervical neoplasia.

PMID- 16280669
TI  - High-resolution immunophenotyping of subcellular compartments in tissue
      microarrays by enzyme metallography.
AB  - Ultrasensitive bright field in situ hybridization assays using enzyme
      metallography (EnzMet) have been developed and validated, but little is known
      regarding the applicability of EnzMet for immunophenotypic detection of protein
      via IHC. Superior resolution via discrete metallographic deposits offers the
      potential for enhancing high-resolution immunophenotyping. Using high-complexity
      tissue microarrays (TMAs), 88 common solid tumors were evaluated by automated
      EnzMet (Nanoprobes and Ventana). Targets were chosen to assess the ability of
      EnzMet to specifically localize encoded antigens in the nucleus (estrogen
      receptor), cytoplasm (cytokeratins), and cytoplasmic membrane (HER2) in TMAs.
      Results were compared with conventional IHC diaminobenzidine (DAB)
      immunostaining. There was full concordance between the EnzMet and conventional
      IHC results. Furthermore, the EnzMet reaction products did not appreciably
      diffuse, were dense and sharply defined, and provided excellent high-resolution
      differentiation of cellular compartments in paraffin sections for the nuclear,
      cytoplasmic, and cell membrane-localized antigens evaluated. The higher density
      of elemental silver deposited during enzyme metallography permitted evaluation of
      core immunophenotypes at a relatively low magnification, allowing more tissue to
      be screened in an efficient manner. This preliminary study shows the utility of
      using enzyme metallography for high-resolution immunophenotyping in TMAs.

PMID- 16280671
TI  - Deep-brain stimulation in Parkinson's disease: long-term efficacy and safety -
      What happened this year?
AB  - PURPOSE OF REVIEW: Deep-brain high-frequency stimulation of the thalamus was
      introduced in 1987 to treat tremor, and was applied in 1993 to the subthalamic
      nucleus to treat advanced Parkinson's disease. High-frequency stimulation of the
      subthalamic nucleus has become the surgical therapy of choice. This review
      concentrates on recent data on long-term results and side-effects, after 12 years
      of practice using this technique. RECENT FINDINGS: A literature search produced
      260 papers from February 2004 to March 2005. The stable efficacy of high
      frequency stimulation of the subthalamic nucleus on Parkinson's disease motor
      symptoms is confirmed. Evidence for a neuroprotective effect is still lacking.
      There are transient neuropsychological disturbances, but no cognitive impairment
      over time. Complications are rare and mild, mortality is extremely low and
      hardware complications are highly variable. SUMMARY: The safety and innocuity of
      the method legitimizes earlier operations, before impairment of the quality of
      life. Depression and suicide are related to pre-existing co-morbidities and
      multifactorial causes that could become contraindications. Neuropsychological
      effects should be documented, to determine whether they are caused by an
      alteration of high-frequency stimulation of the subthalamic nucleus, or
      inappropriate electrode placement. There is an urgent need for the organization
      of research and reports, and no need to report small series replicating well
      established conclusions. Clinical reports should concentrate on unobserved
      effects in relation to causative parameters, based on the precise location of
      electrodes, and on clinical reports comparable between teams and on methods to
      optimize and facilitate the tuning of parameters and postoperative evaluations in
      order to make this treatment easier to provide for the neurologist.

PMID- 16280672
TI  - Neuro-oncology update: 2005.

PMID- 16280673
TI  - Treatment of astrocytomas.
AB  - PURPOSE OF REVIEW: Astrocytomas are the most common primary brain tumors. We will
      review recent developments in the understanding of the biology of these neoplasms
      and recent trials demonstrating promising improvements in the survival of
      patients with malignant gliomas. RECENT FINDINGS: Temozolomide along with
      radiation has become the standard of care for patients with newly diagnosed
      glioblastoma. Nonetheless, despite this advance in treatment, these tumors remain
      incurable. Biological markers and alternative treatment regimens will likely
      improve survival in patients with high-grade gliomas. SUMMARY: A recent study
      demonstrating the benefit of combined temozolomide and radiation provides a
      platform on which to build new treatment regimens. Further developments in the
      understanding of the biology of these tumors will permit specific interventions
      in selected patients that ultimately will improve outcomes.

PMID- 16280674
TI  - An update on oligodendroglial neoplasms.
AB  - PURPOSE OF REVIEW: The most widely accepted brain tumor classification system
      remains morphology-based but the increasing knowledge of the molecular
      pathogenesis of oligodendroglial tumors has spurred translational research
      yielding new diagnostic and therapeutic paradigms. These data have accumulated
      rapidly and, in combination with exciting new insights in the cellular origin of
      these tumors, necessitate a review. RECENT FINDINGS: 'Cancer stem cells' have
      been identified in gliomas. Further study of these cells will not only provide
      information on the cellular origin and pathogenesis of these tumors but may also
      give rise to new treatments that target a cell pool not amenable to current
      therapeutic strategies. Molecular tumor characteristics have been correlated with
      imaging findings, treatment response and prognosis. This has enabled neuro
      oncologists to take a risk-stratified approach to patients with
      oligodendrogliomas that optimizes treatment efficacy and minimizes toxicity.
      Furthermore, more accurate epidemiological data have become available from
      population-based studies. SUMMARY: In spite of remarkable progress over the last
      15 years, these tumors remain incurable. The search for a cure has to go on,
      while currently available multidisciplinary treatments are refined.

PMID- 16280675
TI  - Update on primary central nervous system lymphoma.
AB  - PURPOSE OF REVIEW: Primary central nervous system lymphoma is a rare form of
      extranodal non-Hodgkin's lymphoma that is confined to the central nervous system
      and eye. Numerous studies examining this disorder have been published in the past
      2 years. This review will discuss recent advances in the understanding of the
      pathology, radiographic appearance, and treatment of this disorder. RECENT
      FINDINGS: Novel treatment regimens continue to be studied for newly diagnosed and
      recurrent primary central nervous system lymphoma. As overall survival improves,
      the burden of late neurotoxicity has become more apparent. Neuropsychological
      testing of patients treated with chemoradiation shows significant cognitive
      deficits that can be attributed to whole brain irradiation. Standardization of
      phase II clinical trials across individual institutions remains an important goal
      within the oncology community. The International Primary Central Nervous System
      Lymphoma Collaborative Group (IPCG) has proposed guidelines for the baseline
      evaluation and response criteria for clinical trials of the disorder. In
      addition, series of patients with uncommon histological variants of primary
      central nervous system lymphoma have been published. SUMMARY: In 2005, the
      optimal treatment for primary central nervous system lymphoma remains undefined.
      Treatment of newly diagnosed disease should include methotrexate-based
      chemotherapy but the role of irradiation and intrathecal chemotherapy remain
      unclear. Salvage therapy for progressive or recurrent primary central nervous
      system lymphoma is an area of active interest but no standard recommendations
      exist at the present time. Future studies on the biology of recurrent primary
      central nervous system lymphoma should help to clarify treatment options for
      these patients.

PMID- 16280676
TI  - Brain metastases.
AB  - PURPOSE OF REVIEW: Brain metastases occur in 10-30% of cancer patients, and they
      are associated with a dismal prognosis. Radiation therapy has been the mainstay
      of treatment for patients without surgically treatable lesions. For patients with
      good prognostic factors and a single metastasis, surgical resection is
      recommended. The management of patients with multiple metastases, poor prognostic
      factors, or unresectable lesions is, however, controversial. Recently published
      data will be reviewed. RECENT FINDINGS: Radiation therapy has been shown to
      substantially reduce the risk of local recurrence after surgical resection of
      brain metastases, although this does not translate into improved survival.
      Recently, stereotactic radiosurgery has emerged as an increasingly important
      alternative to surgery that appears to be associated with less morbidity and
      similar outcomes. Other potentially promising therapies under investigation
      include interstitial brachytherapy, new chemotherapeutic agents that cross the
      blood-brain barrier, and targeted molecular agents. SUMMARY: Patients with brain
      metastases are now eligible for a number of treatment options that are
      increasingly likely to improve outcomes. Randomized, prospective trials are
      necessary to better define the utility of radiosurgery versus surgery in the
      management of patients with brain metastases. Future investigations should
      address quality of life and neurocognitive outcomes, in addition to traditional
      outcome measures such as recurrence and survival rates. The potentially
      substantial role for chemotherapeutics that cross the blood-brain barrier and for
      novel targeted molecular agents is now being elucidated.

PMID- 16280677
TI  - Cognitive sequelae of brain tumor treatment.
AB  - PURPOSE OF REVIEW: The neurocognitive sequelae of anticancer treatment have
      received increasing attention especially among individuals with low-grade
      gliomas, primary central nervous system lymphoma and those undergoing
      prophylactic cranial irradiation for systemic malignancies. These groups are
      especially vulnerable because they often experience extended survival during
      which neurocognitive complications of therapy may cause more impairment than the
      tumor itself. The purpose of this review is to highlight recent clinical reports
      of neurocognitive sequelae among patients without significant central nervous
      system tumor burden and to describe the experimental studies which may explain
      the pathogenesis of the disorder. RECENT FINDINGS: The neurocognitive deficits
      among survivors of primary central nervous system lymphoma without residual tumor
      and pituitary tumors were reported recently. Both provide an opportunity to
      distinguish the effects of treatment from the effects of tumor. Moreover, animal
      studies demonstrate the negative consequences of radiation on hippocampal
      neurogenesis, learning and memory. The mechanism of impaired neurogenesis may be
      due to inflammation, which can be aborted with restoration of neurogenesis
      through the administration of non-steroidal anti-inflammatory agents. SUMMARY: If
      inhibition of neurogenesis is the basis of neurocognitive sequelae from
      irradiation and non-steroidal anti-inflammatory agents can restore neurogenesis
      then a clinical trial may be worthwhile to confirm this benefit in humans.

PMID- 16280678
TI  - Drivers of brain plasticity.
AB  - PURPOSE OF REVIEW: Neural plasticity represents a crucial mechanism of the human
      brain to adapt to environmental changes in the developing and adult human central
      nervous system. This property of the central nervous system contributes to
      learning and functional recovery from neurological diseases such as stroke. Novel
      interventional approaches have been proposed and are under investigation to
      modulate neural plasticity, enhance it when it plays an adaptive role and
      downregulate it when it is considered maladaptive. RECENT FINDINGS: One of the
      purposes of research in neurorehabilitation has been to develop interventional
      approaches to enhance the beneficial effects of training. Procedures like
      cortical stimulation, administration of central nervous system active drugs and
      modulation of afferent input have been evaluated as drivers of neural plasticity
      in healthy subjects and in small groups of patients with stroke. So far, these
      studies have shown promising results and translation into the clinic is under
      investigation. SUMMARY: Cortical stimulation and purposeful changes in afferent
      input that modulate neural plasticity impact on behavioral markers of
      performance, learning and functional recovery and represent promising tools in
      neurorehabilitation.

PMID- 16280679
TI  - Neuropharmacological modulation of cognitive deficits after brain damage.
AB  - PURPOSE OF REVIEW: This review discusses recent studies that have implications
      for potential neuropharmacological interventions which target cognitive deficits
      resulting from traumatic brain injury or stroke. RECENT FINDINGS: An important
      new study concerning the activity of N-methyl-D-aspartate (NMDA) receptors after
      brain injury reveals that previous influential hypotheses about an increase in
      glutamate triggering neuronal death may need to be revised. Furthermore, the
      study suggests that cognitive function may be best preserved by stimulation of
      NMDA receptors with agonists rather than by the use of antagonists, as previously
      believed. Investigations of animal models of stroke and traumatic brain injury
      have further demonstrated the possibility of intervening in the acute and sub
      acute stages to protect specific brain systems, such as preservation of the
      cholinergic system (via cholinesterase inhibitors) and hippocampal neurons (via a
      D2 agonist). Clinical trials in humans indicate it is also possible to target
      these neurotransmitter systems to enhance cognitive performance in patients with
      chronic deficits. In particular, recent studies demonstrated that it is possible
      to ameliorate the effects of two common cognitive syndromes, visual neglect and
      aphasia. SUMMARY: Cognitive deficits are an extremely common consequence of
      either traumatic brain injury or stroke. Recent studies demonstrate the potential
      for using neuropharmacological intervention after acquired brain injury to
      prevent or ameliorate the effects of cognitive impairments. These treatments,
      however, are still in their preliminary stages and further research is required
      to identify the most effective compounds.

PMID- 16280680
TI  - Assessment of subjective health and health-related quality of life in persons
      with acquired or degenerative brain injury.
AB  - PURPOSE OF REVIEW: Health-related quality of life is a new outcome variable in
      neurology. Several generic measures aim at assessing this variable in adults with
      neurological diseases. Disease-specific measures are still rare; however,
      individuals with neurological diseases frequently suffer from cognitive
      impairment, yet are often excluded from health-related quality of life
      investigations. When included in such studies, cognitive functioning is not
      monitored via neuropsychological evaluation, possibly leading to methodological
      problems. Papers from May 2004 until July 2005 are reviewed with respect to
      psychometric quality and information about persons after traumatic brain injury,
      stroke, Parkinson's disease or dementia. RECENT FINDINGS: Several new cross
      sectional and longitudinal outcome studies are reviewed. The Medical Outcome
      Study Short Form with 36 items, the Sickness Impact Profile and the Nottingham
      Health Profile were identified as the most frequently used measures in neurology.
      For traumatic brain injury, two new generic instrument validations (Life
      Satisfaction Index-A, Subjective Quality of Life Profile) and one internationally
      validated disease-specific development (Quality of Life after Brain Injury) were
      found; for stroke, one disease-specific tool (Burden of Stroke Scale) was
      identified. In Parkinson's disease, the disease-specific health-related quality
      of life measure Parkinson's Disease Questionnaire-39 is well validated. In
      dementia, three dementia-specific instruments (Quality of Life for Dementia,
      Quality of Life in Late-Stage Dementia Scale and Quality of Life in Alzheimer's
      Disease Scale) seem to be valid. SUMMARY: In neurology, only a few measures have
      been developed and validated for respondents with cognitive impairment, often
      showing poorer validity results than studies involving healthy persons. Health
      related quality of life assessment should therefore be validated in the specific
      diseases and, if necessary, combined with a neuropsychological evaluation and a
      disease-specific health-related quality of life measure.

PMID- 16280681
TI  - Rehabilitation interventions after mild head injury.
AB  - PURPOSE OF REVIEW: This review examines current management and rehabilitation
      strategies for mild traumatic brain injury, with emphasis on the need to address
      multiple potential causative factors in order to enhance outcomes and to conduct
      more controlled efficacy studies. RECENT FINDINGS: Whilst most individuals who
      sustain mild traumatic brain injury make a good recovery, a proportion experience
      significant ongoing disability. In some cases this is due to diffuse axonal
      injury and cognitive impairment, but in others symptoms are exacerbated by
      factors such as pain, stress, personality issues or litigation, or in children,
      previous head injury, behavioural or learning difficulties. Provision of
      information early after injury results in reduced symptom reporting in adults and
      children. There is also a need, however, to address these other factors in
      treatment. Psychological therapy using a cognitive behavioural approach may be
      helpful, but controlled evaluations of such interventions have been lacking.
      Recent uncontrolled studies have examined the impact of computer-mediated
      interventions to remediate visual and verbal processing and oculomotor problems
      and the impact of quantitative electroencephalography. More rigorous efficacy
      studies of these approaches are needed. Guidelines for management of sports
      related concussion and timing of return to play also require a more solid
      scientific basis. SUMMARY: The evidence base for management of mild traumatic
      brain injury is still very limited. There is a need to conduct more carefully
      controlled prospective studies and examine the influence of factors not directly
      related to the brain injury as a basis for formulating more uniform management
      guidelines.

PMID- 16280682
TI  - Biomarkers for neurodegenerative diseases.
AB  - PURPOSE OF REVIEW: A major goal of current clinical research in neurodegenerative
      diseases is to improve early detection of disease and presymptomatic detection of
      neuronal dysfunction. We also need better tools to assess disease progression in
      this group of disorders. Currently, many potential disease-modifying therapies
      are being developed and evaluated at the preclinical stage, and will lead to
      clinical trials in the near future for which biomarkers are urgently needed. This
      review summarizes the field of biomarker research in the major neurodegenerative
      diseases. RECENT FINDINGS: Many different approaches are being undertaken to
      identify biomarkers and include imaging, neurophysiological and cognitive testing
      in addition to newer technologies such as biochemical, proteomic, metabanomic and
      gene array profiling of tissue and biofluids from patients. Key recent findings
      in each of these areas are discussed. SUMMARY: The ideal biomarker needs to be
      easy to quantify and measure, reproducible, not subject to wide variation in the
      general population and unaffected by co-morbid factors. For evaluation of
      therapies the biomarker needs to change linearly with disease progression and
      closely correlate with established clinico-pathological parameters of the
      disease. It is unlikely that any one biomarker will fulfil all these
      characteristics, and it is likely that more than one biomarker will be needed for
      early diagnosis and similarly for evaluation of disease progression for
      therapeutic trials. For example, the combination of more detailed clinical
      assessments encompassing specific cognitive and neurophysiological testing, in
      addition to imaging, biochemical and genomic profiling, is likely to be needed.

PMID- 16280683
TI  - How genetics research in Parkinson's disease is enhancing understanding of the
      common idiopathic forms of the disease.
AB  - PURPOSE OF REVIEW: Rapid progress in genetics has meant that there are now five
      genes identified for 'Parkinson's disease'. The detailed phenotypes vary, but
      generally the dominant genes cause a Lewy body disease spectrum whereas recessive
      genes cause a milder parkinsonism with variable inclusion body pathology. The
      subject of this review is to highlight these discoveries and to discuss their
      relationships to idiopathic Parkinson's disease. RECENT FINDINGS: In January
      2004, mutations in PINK1, coding for a mitochondrial kinase, were found to be
      causal for recessive parkinsonism. Subsequently, several studies have found
      additional mutations associated with early onset parkinsonism. Some cases have
      been described with a phenotype much closer to idiopathic Parkinson's disease,
      but it does not appear that PINK1 is a major risk factor for the sporadic
      disease. Later in the same year, the LRRK2 gene was shown to cause a dominant
      disease with a broader phenotype. The protein product was named dardarin and
      contains GTPase and kinase domains. Lewy bodies have been reported in LRRK2
      cases, potentially linking this gene with sporadic Parkinson's disease. One
      mutation, G2019S, is found in a significant percentage of cases, including
      sporadic Parkinson's disease. SUMMARY: Mutations in these two genes, along with
      previously described Mendelian variants, are beginning to yield important
      information about loss of specific neuronal groups or to protein inclusion
      pathology. How this relates to sporadic Parkinson's disease, however, is not yet
      fully defined. There are clear phenotypic overlaps with genetic and sporadic
      Parkinson's disease, especially for the dominant genes, suggesting that common
      facets of pathogenesis may exist.

PMID- 16280684
TI  - Amyotrophic lateral sclerosis: recent advances and future therapies.
AB  - PURPOSE OF REVIEW: Amyotrophic lateral sclerosis is a rare but fatal motoneuron
      disorder. Despite intensive research riluzole remains the only available therapy,
      with only marginal effects on survival. Here we review some of the recent
      advances in the search for a disease-modifying therapy for amyotrophic lateral
      sclerosis. RECENT FINDINGS: A number of established agents have recently been re
      investigated for their potential as neuroprotective agents, including beta-lactam
      antibiotics and minocycline. Progress has also been made in exploiting growth
      factors for the treatment of amyotrophic lateral sclerosis, partly due to
      advances in developing effective delivery systems to the central nervous system.
      A number of new therapies have also been identified, including a novel class of
      compounds, heat-shock protein co-inducers, which upregulate cell stress responses
      thereby mediating neuroprotection. Non-drug-based therapies are also under
      development, with progress in gene-silencing and stem cell therapies. SUMMARY: In
      the past few years, significant advances have been made in both our understanding
      of amyotrophic lateral sclerosis pathogenesis and the development of new
      therapeutic approaches. However, caution must be exercised in view of the long
      standing failure to successfully transfer therapeutic compounds to the clinic. A
      deeper awareness in the research community of the need for clinically relevant
      preclinical studies, coupled with a better understanding of the issues
      surrounding clinical trial design for amyotrophic lateral sclerosis, offers hope
      that the growing list of validated preclinical therapeutics can finally yield an
      effective disease-modifying treatment.

PMID- 16280685
TI  - Immunotherapy for Alzheimer's disease and other dementias.
AB  - PURPOSE OF REVIEW: The aim of this article is to review the role of immunotherapy
      in the removal of proteins which accumulate abnormally in neurodegenerative
      disorders associated with dementia, in particular amyloid-beta accumulation in
      Alzheimer's disease. RECENT FINDINGS: In both transgenic mouse models and in two
      trials of amyloid-beta immunotherapy for human Alzheimer's disease, active
      immunization with amyloid-beta 1-42 results in the removal of amyloid-beta
      plaques from the cerebral cortex associated with, in the mouse models,
      improvement in cognitive function. Cerebral amyloid angiopathy and
      neurofibrillary tangles persist, however, and there is also concern about T
      lymphocyte immune reactions in the meninges in the human cases. Active
      immunization schedules are being developed to minimize T lymphocyte reactions and
      to maximize antibody production and passive immunization protocols are being
      devised. Immunotherapy for removal of the proteins which accumulate in other
      neurodegenerative disorders associated with dementia such as prion proteins and
      alpha-synuclein are in the early stages of development. SUMMARY: Dementias in the
      elderly are an increasing medical, social and economic problem and current
      treatments are only effective. In the majority of dementias, proteins accumulate
      within cells and in the extracellular compartments of the brain. In the most
      common dementia, Alzheimer's disease, amyloid-beta accumulates as plaques in the
      extracellular space of the grey matter and in artery walls as cerebral amyloid
      angiopathy and tau protein accumulates as neurofibrillary tangles within neurons.

PMID- 16280686
TI  - Residual cognitive function in comatose, vegetative and minimally conscious
      states.
AB  - PURPOSE OF REVIEW: The clinical evaluation of cognition in non-communicative
      severely brain-damaged patients is inherently difficult. In addition to novel
      behavioural 'consciousness-scales', the role of para-clinical markers of
      consciousness, such as event related potentials and functional neuroimaging is
      reviewed. RECENT FINDINGS: New behavioural scales for vegetative and minimally
      conscious patients have been shown to reduce diagnostic error but regrettably
      remain underused in clinical routine. Electrophysiological studies have confirmed
      their role in estimating outcome and possibly cognition. Several recent
      functional neuroimaging studies have shown residual cortical function in
      undeniably vegetative patients. This cortical activation, however, seems limited
      to primary 'low-level' areas and does not imply 'higher-order' integration,
      considered necessary for conscious perception. Minimally conscious patients show
      large-scale high-order cerebral activation, apparently dependent upon the
      emotional relevance of the stimulation. SUMMARY: Careful clinical assessment of
      putative 'conscious behaviour' in vegetative and minimally conscious patients is
      the first requirement for their proper diagnosis and management. Complementary
      functional neuroimaging and electrophysiological studies will have a major impact
      on future clinical decision making and may guide selective therapeutic options.
      At present, more experimental evidence and the elucidation of methodological and
      ethical controversies are awaited prior to their routine clinical use.

PMID- 16280687
TI  - Decision-making and impulse control after frontal lobe injuries.
AB  - PURPOSE OF REVIEW: For a long time, the prefrontal cortex has been considered a
      'nonfunctional' brain area, and understanding its function has lagged behind
      other areas. This is no longer true since appreciation of the vital role that
      this brain region plays in adaptive behaviors, and especially decision-making, is
      now evident more than ever. The present review highlights recent progress made in
      this area of research. RECENT FINDINGS: Decision-making is a term often referred
      to in the psychological literature as one of the 'executive functions' that play
      a role in managing (like an executive) other cognitive functions, such as memory,
      attention, and language. Considerable research efforts have been directed towards
      differentiating various processes of executive functions, but much of this effort
      in the past has focused on the dorsolateral prefrontal cortex sector. Here we
      will review findings that address decision-making and its link to the
      ventromedial prefrontal cortex. SUMMARY: Decision-making impairments as
      encountered in neurological and psychiatric patients are costly in terms of
      individual human suffering and in financial terms. In addition to its obvious
      value in advancing fundamental knowledge in neuroscience, understanding the
      neural mechanisms of decision-making is likely to have important practical
      consequences, including the understanding and management of neuropsychiatric
      disorders such as addiction, as well as the management of a considerable number
      of elderly people suffering from a decline in cognitive functions critical for
      decision-making, in spite of relatively intact memory and general intellect,
      which impact real-life matters that are important to themselves and their family.

PMID- 16280688
TI  - Healthy and pathological processes in adult development: new evidence from
      neuroimaging of the aging brain.
AB  - PURPOSE OF REVIEW: Recent research has revealed that the population of older
      adults is composed not only of individuals who are either healthy or have an age
      related disease, most commonly Alzheimer's disease, but also individuals with
      mild cognitive impairment who are at-risk for or already in the prodromal stage
      of Alzheimer's disease. These variations in cognitive aging can be related to
      their neural bases via structural and functional neuroimaging methods. RECENT
      FINDINGS: Healthy aging appears to primarily affect a frontal-striatal system
      that undergirds executive control of cognition, while minimally affecting medial
      temporal lobe structures. Functional imaging studies suggest that enhanced
      prefrontal engagement may offer compensatory plasticity that minimizes age
      related cognitive losses. Mild cognitive impairment appears to affect the
      entorhinal cortex in particular, with functional consequences in other brain
      regions. Alzheimer's disease is characterized by severe hippocampal injury,
      although early-stage Alzheimer's disease may relatively spare some cortical
      regions. SUMMARY: Advances in in-vivo imaging methods are providing the tools for
      identifying different trajectories of neurocognitive aging, and knowledge about
      these brain changes may promote opportunities for treatment.

PMID- 16280689
TI  - The neurological basis of visual neglect.
AB  - PURPOSE OF REVIEW: A recent study has confirmed the enormous impact of visual
      neglect on the health services of the western world. Neglect was present in 48%
      of a sample of 166 right hemisphere stroke patients, and the severity of neglect
      predicted the extent of functional disability and family burden more accurately
      than did the extent of brain damage. Given the medical significance of neglect
      and its tantalizing relevance to understanding human conscious experience, it is
      unsurprising that the neuropsychological literature concerning the syndrome
      continues to grow rapidly. RECENT FINDINGS: We include brief surveys of six
      topics currently attracting attention in the field: the anatomical focus of
      neglect; the visual input pathways implicated; impairments of spatial working
      memory; the nature of visual extinction; perceptual distortions in neglect;
      studies on healthy subjects using transcranial magnetic stimulation; and the use
      of prism adaptation for the rehabilitation of neglect. SUMMARY: There is steady
      progress in understanding the essential components of neglect and their brain
      localization. Every step towards clarity, however, seems to be matched by a new
      discovery of the inherent complexity of the syndrome. The clinical expression of
      neglect may reflect the interaction of a variety of spatially lateralized and non
      lateralized impairments, not all of which are present in all patients. The quest
      for an effective technique for the clinical rehabilitation of neglect continues,
      with prism adaptation emerging as the most promising approach to date.

PMID- 16280691
TI  - A CCR5-tropic simian-HIV molecular clone capable of inducing AIDS in rhesus
      macaques.
AB  - We previously reported the derivation of a CCR5 (R5)-tropic pathogenic strain
      SHIVSF162P3. Here, we show that a simian-HIV (SHIV) molecular clone expressing
      the entire env gp160 of SHIVSF162P3, termed SHIV P3gp160, could fully
      recapitulate the in vivo replicative characteristics of the parental isolate.
      SHIV P3gp160 is mucosally transmissible, preferentially depletes memory CD4 T
      cells, and induced simian AIDS in 2 of 6 infected macaques. The availability of
      an infectious R5 SHIV molecular clone that can be transmitted mucosally and
      causes disease provides an important reagent for studies of lentiviral
      pathogenesis and AIDS vaccine research.

PMID- 16280692
TI  - A transcription inhibitor, actinomycin D, enhances HIV-1 replication through an
      interleukin-6-dependent pathway.
AB  - We previously demonstrated that Actinomycin D (ActD) enhanced HIV-1 replication
      in the MT-2 cell, a human T-cell leukemia virus type-1-infected cell line. The MT
      2 cell is known to produce multiple cytokines spontaneously. In this study, we
      investigated the impact of ActD on the cytokine production from MT-2 cells and
      HIV-1 replication in a latently infected cell line, U1. MT-2 cells were pulse
      treated with 0 or 200 nM of ActD, and culture supernatants were collected 3 days
      after incubation. Supernatants from untreated cells (Sup0) induced HIV-1
      replication by 150-fold in U1 cells. Culture supernatants from ActD-treated cells
      (Sup200) enhanced HIV-1 replication by 1200-fold. A combination of a sequential
      chromatographic approach and mass spectrometric analysis identified that the HIV
      inducing factors in Sup200 were interleukin (IL)-6 and tumor necrosis factor
      (TNF)-beta. Quantitative analysis revealed that ActD treatment increased the
      concentration of IL-6 in Sup200 by 600% compared with that in Sup0 but decreased
      the amount of TNFbeta in Sup200 by 85%. Northern blot analysis showed that ActD
      treatment increased IL-6 transcripts; however, no change was seen in TNFbeta
      transcripts. These results suggest that ActD induces replication of HIV-1 through
      modulation of cytokine production.

PMID- 16280693
TI  - Direct comparison of the acute in vivo effects of HIV protease inhibitors on
      peripheral glucose disposal.
AB  - The clinical use of HIV protease inhibitors (PIs) is associated with the
      development of peripheral insulin resistance. The incidence and degree of
      impaired glucose tolerance observed in treated patients vary considerably between
      drugs, however. To compare the ability of HIV PIs to alter peripheral glucose
      disposal acutely in a genetically identical model system at therapeutically
      relevant drug levels, healthy lean male rats previously naive to PI exposure were
      given ritonavir, amprenavir, lopinavir/ritonavir (4:1), or atazanavir by
      continuous intravenous infusion to achieve steady state drug levels of 10 or 25
      muM rapidly. Under euglycemic hyperinsulinemic clamp conditions, a dose-dependent
      reduction in the peripheral glucose disposal rate (Rd) was observed with all the
      PIs except atazanavir. The rank order of sensitivity was ritonavir, lopinavir,
      and then amprenavir. Changes in skeletal muscle and heart 2-deoxyglucose (2-DOG)
      uptake correlated with reductions in Rd. All 3 of these PIs also produced
      significant reductions in 2-DOG uptake into primary rat adipocytes in vitro.
      Atazanavir had no effect on glucose uptake in vitro or in vivo. The in vivo
      potency of PIs to impair peripheral glucose disposal acutely correlates with the
      degree of insulin resistance observed in HIV-infected patients receiving these
      drugs. Preclinical testing of novel candidate PIs in a rodent model system may be
      useful in identifying the future risk of altering glucose homeostasis.

PMID- 16280694
TI  - Durable efficacy of enfuvirtide over 48 weeks in heavily treatment-experienced
      HIV-1-infected patients in the T-20 versus optimized background regimen only 1
      and 2 clinical trials.
AB  - BACKGROUND: The T-20 Versus Optimized Background Regimen Only (TORO) 1 and TORO 2
      clinical trials are open-label, controlled, parallel-group, phase 3 studies
      comparing enfuvirtide plus an optimized background (OB) of antiretrovirals (n =
      661) with OB alone (n = 334) in treatment-experienced HIV-1-infected patients.
      METHODS: The primary objective at week 48 was to investigate durability of
      efficacy, as measured by the percentage of patients maintaining their week 24
      response or improving. Efficacy analyses used the intent-to-treat population.
      RESULTS: A total of 73.7% of patients randomized to the enfuvirtide group
      remained on treatment through week 48 versus 21.3% originally randomized to the
      control group. At week 48, a higher proportion of week 24 responders maintained
      their response or were new responders in the enfuvirtide group than in the
      control group in each responder category: HIV-1 RNA level > or =1.0 log(10)
      change from baseline, <400 copies/mL and <50 copies/mL (37.4%, 30.4%, and 18.3%
      in the enfuvirtide group vs. 17.1%, 12.0%, and 7.8% in the control group,
      respectively; P < 0.0001 for all comparisons). CD4 cell count increases from
      baseline were twice as great in the enfuvirtide group as in the control group.
      CONCLUSION: These data demonstrate durable efficacy of enfuvirtide plus OB over
      48 weeks.

PMID- 16280695
TI  - Safety of enfuvirtide in combination with an optimized background of
      antiretrovirals in treatment-experienced HIV-1-infected adults over 48 weeks.
AB  - BACKGROUND: Antiretroviral tolerability is a critical factor contributing to
      treatment outcome. The T-20 Versus Optimized Background Regimen Only (TORO)
      studies assessed the safety and efficacy of enfuvirtide in treatment-experienced
      HIV-1-infected patients. METHODS: A total of 997 patients were randomized at a
      2:1 ratio to an optimized background antiretroviral regimen plus enfuvirtide (n =
      663) or an optimized background regimen alone (control group; n = 334). Control
      patients could switch to enfuvirtide on virologic failure. RESULTS: In total,
      26.5% of patients randomized to enfuvirtide and 36.6% to the control group
      discontinued study treatment before week 48; the percentage of patients withdrawn
      for safety reasons (including adverse events [AEs], deaths, and laboratory
      abnormalities) was 14.0% in the enfuvirtide group and 11.6% in the control group.
      Injection site reactions (ISRs) occurred in 98% of enfuvirtide patients and led
      to treatment discontinuation in 4.4%. Treatment-related (defined as possibly,
      probably, or remotely) AE rates per 100 patient-years were lower with enfuvirtide
      (96.2) than in the control group (149.9); diarrhea, nausea, and fatigue, the most
      frequently reported AEs, were significantly less frequent with enfuvirtide than
      in the control group. Pneumonia was significantly more frequent in patients
      treated with enfuvirtide (6.7 vs. 0.6 events per 100 patient-years), although the
      incidence was within expected ranges for this population. Lymphadenopathy was
      also higher in enfuvirtide-treated patients (7.1 vs. 1.2 events per 100 patient
      years) for control patients. CONCLUSION: The addition of enfuvirtide to an
      optimized background regimen does not exacerbate AEs commonly associated with
      antiretrovirals. ISRs limited treatment in <5% of patients.

PMID- 16280696
TI  - Abacavir and lamivudine fixed-dose combination tablet once daily compared with
      abacavir and lamivudine twice daily in HIV-infected patients over 48 weeks
      (ESS30008, SEAL).
AB  - BACKGROUND: Abacavir (ABC) and lamivudine (3TC) administered twice daily were
      compared with an ABC + 3TC fixed-dose combination (Epzicom, Kivexa; EPZ)
      administered once daily, both in combination with a protease inhibitor (PI) or
      nonnucleoside reverse transcriptase inhibitor (NNRTI). METHODS: Two hundred sixty
      HIV-infected subjects with more than 6 months of ABC and 3TC administered twice
      daily plus a PI or NNRTI with an HIV-1 RNA level less than 400 copies/mL for more
      than 3 months and a CD4 count greater than 50 cells/mm were randomized 1:1 to ABC
      + 3TC administered twice daily or EPZ administered once daily. RESULTS: At
      baseline, median time on ABC and 3TC administered twice daily was 22 months, and
      median CD4 count and HIV-1 RNA level were 554 cells/mm and <50 copies/mL,
      respectively. EPZ administered once daily was established as not inferior to ABC
      + 3TC administered twice daily based on the proportion of nonvirologic failures
      (confirmed HIV-1 RNA level > or =1265 copies/mL; 90% confidence interval: -3.4 to
      6.4; (intent to treat [ITT]: missing [M] = failure [F]). Proportions with an HIV
      1 RNA level <50 copies/mL were 81% of those taking EPZ once daily and 82% of
      those taking ABC + 3TC twice daily at week 48 (ITT: M = F). Virologic failure was
      rare (2 patients taking the once-daily regimen, 4 patients taking the twice-daily
      regimen). There was a low incidence of grade 2 through 4 adverse events (AEs) and
      no drug-related serious AEs or hypersensitivity reactions. CONCLUSIONS: EPZ
      administered once daily was established as not inferior to ABC + 3TC administered
      twice daily in a regimen containing an NNRTI or a PI over 48 weeks. A dual
      nucleoside backbone of ABC and 3TC administered once or twice daily is effective,
      durable, and well tolerated.

PMID- 16280697
TI  - Quality of life in a clinical trial of highly active antiretroviral therapy alone
      or with intravenous or subcutaneous interleukin-2 administration.
AB  - OBJECTIVE: To assess the impact of subcutaneous and intravenous interleukin-2 (IL
      2) on health-related quality of life (HRQOL) in adults with HIV-1 receiving
      highly active antiretroviral therapy (HAART). DESIGN: Randomized clinical trial.
      SETTING: Twenty-two institutions from the Adult AIDS Clinical Trials Group.
      PATIENTS: One hundred forty-eight HIV-infected adults randomized, with baseline
      HRQOL data. METHODS: HAART (indinavir plus 2 nucleoside analogues) for 12 weeks,
      followed by 72 weeks of continued HAART alone, HAART plus subcutaneous IL-2, or
      HAART plus intravenous IL-2. OUTCOME MEASURES: Scores for 8 dimensions of HRQOL,
      an unweighted summary score, and a visual analogue health rating score. RESULTS:
      The IL-2 subcutaneous group had the best mean change in 6 of 8 dimension
      subscales and in the summary scale at 28 weeks (16 weeks after baseline). At 52
      weeks, the IL-2 subcutaneous group had the best mean change in all the subscales
      and the summary scale. The differences were statistically significant for 3
      subscales and the summary scale. Midcycle changes were statistically
      significantly worse for the subcutaneous IL-2 group for 4 subscales and the
      summary scale. CONCLUSIONS: We found evidence of a short-term but not long-term
      adverse impact of IL-2 on HRQOL and some evidence of long-term benefit for the
      subcutaneous group.

PMID- 16280698
TI  - Validation of a brief screening instrument for substance abuse and mental illness
      in HIV-positive patients.
AB  - BACKGROUND: Substance abuse (SA) and mental illness (MI) commonly co-occur with
      HIV infection in the United States and have important implications for clinical
      management of HIV/AIDS. Yet SA/MI often go untreated due in part to a lack of
      practical, validated screening tools. SETTING: HIV clinic in academic medical
      center. METHODS: The 16-item SA/MI Symptoms Screener (SAMISS) targets SA/MI in
      HIV-positive patients. Consecutive consenting HIV-positive patients completed the
      SAMISS and then a reference standard diagnostic tool, SCID, the Structured
      Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition). RESULTS: Twenty percent of participants (29/148) had
      an SA diagnosis and 41% (59/143) had an MI diagnosis in the past year on the
      SCID; 48% (68/143) had 1 or both. Thirty-seven percent (55/148) screened positive
      for SA and 69% (99/143) screened positive for MI on the SAMISS. The SAMISS had
      86% (95% CI: 68%-96%) sensitivity and 75% (66%-82%) specificity for SA and 95%
      (86%-99%) sensitivity and 49% (38%-60%) specificity for MI. Patients with SA were
      likely to show up as false positives for MI and vice versa. CONCLUSION: The
      SAMISS functioned well as a first-line screening tool for SA/MI in this HIV
      clinic population. It missed few cases and was easily incorporated into a busy
      clinical setting. Persons screening positive require a more rigorous confirmatory
      psychiatric evaluation.

PMID- 16280699
TI  - Predictors of mortality for patients with advanced disease in an HIV palliative
      care program.
AB  - BACKGROUND: Despite advances in treatment, AIDS and its associated comorbidities
      remain important causes of death. Traditional HIV prognostic markers may be less
      useful in predicting death in current late-stage patients than in the era before
      highly active antiretroviral therapy. METHODS: We used standardized baseline and
      follow-up data to describe causes of death and predictors of mortality in a
      cohort of patients with advanced disease referred to a specialized HIV palliative
      care program at a large urban medical center. RESULTS: Of 230 patients, 56% were
      male with a median age of 43 years; 54% were Hispanic and 39% were African
      American; 41% had a history of injection drug use; 89% had prior AIDS-defining
      illnesses; and median baseline values included a CD4 count of 39 cells/mm, HIV
      viral load of 65,202 copies/mL, Karnofsky score of 30, and 5 impaired activities
      of daily living (ADL). Over a median follow-up of 126 days (range: 1-823 days),
      120 patients died; 54% of these died of late-stage HIV disease and/or bacterial
      pneumonia or sepsis, 19% of non-AIDS-defining cancers, 13% of liver failure
      and/or cirrhosis, and 12% of other progressive end-organ disease (eg, cardiac,
      pulmonary, renal). On multivariate analysis, death was predicted only by age (>65
      years), baseline number of ADL impairments, and Karnofsky score (P < 0.0001 for
      all) and not by any AIDS-specific variables. CONCLUSIONS: For patients with late
      stage disease referred to an HIV palliative care program, age and markers of
      functional status were more predictive of mortality than traditional HIV
      prognostic variables. Close to half of all deaths were attributable to non-AIDS
      specific causes, including cancer and end-organ failure. These findings suggest
      the need for renewed study of predictors of mortality and prognostic markers in
      patients with advanced HIV disease and related comorbidities in the HAART era.

PMID- 16280700
TI  - A 12-month treatment with tenofovir does not impair bone mineral accrual in HIV
      infected children.
AB  - BACKGROUND: Short-term use of tenofovir (TDF) has been associated with bone
      mineral loss in adults and children. OBJECTIVE: To assess whether the
      substitution of stavudine with TDF would result in decreased bone mineral content
      (BMC) and bone mineral density (BMD) accrual in HIV-infected children. METHODS:
      The lumbar spine and whole-body BMC and BMD were measured by dual-energy x-ray
      absorptiometry in 16 HIV-infected children (age range: 6.4-17.9 years) on stable
      highly active antiretroviral therapy. Bone measurements were obtained 12 months
      before the switch, at baseline, and 12 months after switching to TDF. Expected
      changes in bone measurements were calculated from cross-sectional data obtained
      from 166 healthy children. RESULTS: The BMC and BMD increments observed before
      switching therapy did not differ from expected increments. Similarly, the changes
      detected during treatment with TDF did not differ significantly from those
      calculated in healthy controls. CONCLUSIONS: Substitution to a TDF-containing
      antiretroviral regimen does not seem to impair bone mineral accrual in children
      showing a good immunologic response to antiretroviral treatment.

PMID- 16280701
TI  - A population-based analysis of temporal trends in the incidence of squamous anal
      canal cancer in relation to the HIV epidemic.
AB  - Squamous cell carcinoma of the anal canal (SCCA) is etiologically linked to human
      papillomavirus, and its incidence is increased among the immunosuppressed. We
      used data from the Surveillance, Epidemiology, and End Results program to analyze
      the incidence of SCCA in relation to 3 separate periods during the HIV epidemic:
      the pre-HIV era (1973-1981), the HIV era (1982-1995), and the highly active
      antiretroviral treatment (HAART) era (1996-2001). The incidence per 100,000
      population of SCCA increased from 0.6 in the pre-HIV era to 0.8 in the HIV era
      and to 1.0 in the HAART era. The gap in SCCA incidence between women and men
      decreased from a ratio of 1.6:1 in the pre-HIV era to 1.5:1 in the HIV era and to
      1.2:1 in the HAART era. There was a significant increase in incidence rates among
      men and women aged 30 to 54 years in the HAART era compared with the HIV era. Men
      were more likely to be diagnosed with early-stage disease, but they were less
      likely than women to receive radiation therapy. The incidence of SCCA has
      particularly increased among men and those between 30 and 54 years of age since
      the introduction of HAART.

PMID- 16280702
TI  - Distribution of HIV-1 variants in the Democratic Republic of Congo suggests
      increase of subtype C in Kinshasa between 1997 and 2002.
AB  - The Democratic Republic of Congo (DRC) is characterized by low and stable HIV
      prevalences and high HIV-1 genetic diversity and is most probably the epicenter
      of HIV-1 group M. Our major goal was to study the distribution of HIV-1 variants
      over a 5-year period against a background of political instability and civil war.
      A total of 288 HIV-1-positive samples collected in 2002 from sentinel population
      groups in an HIV serosurveillance study performed in 4 cities (Kinshasa [capital
      city], Mbuji-Mayi [south], Lubumbashi [southeast], and Kisangani [northeast])
      were genetically characterized by sequencing and phylogenetic analysis of the V3
      V5 env region. The results were compared with those obtained in 1997. Similarly,
      as in 1997, an extremely high genetic diversity of HIV-1 strains overall and a
      heterogeneous geographic distribution were seen in 2002. All subtypes and several
      circulating recombinant forms were present, high intrasubtype diversity was
      observed, and 5.6% of the samples could not be classified. In each geographic
      region of the DRC, the genetic diversity was significantly higher than in
      neighboring countries. Comparison of subtype distribution in similar population
      groups in Kinshasa in 1997 and 2002 revealed an overall increase of subtype C in
      Kinshasa from 2.1% to 9.7% and, more precisely, from 0% to 18.9% in female sex
      workers (P = 0.013). Genetic characterization of HIV-positive samples from
      sentinel surveys adds significant additional information on new trends in the HIV
      epidemic. These changes could have implications regarding the spread of HIV
      infection in the DRC as well on vaccine and/or treatment strategies.

PMID- 16280703
TI  - High-risk sexual behavior in adults with genotypically proven antiretroviral
      resistant HIV infection.
AB  - BACKGROUND: The substantial frequency of drug resistance in persons recently
      infected with HIV implies exposure among HIV-uninfected individuals to HIV
      infected persons with drug-resistant virus. Although there is an increasing
      emphasis on understanding high-risk behavior among HIV-infected patients, little
      work has focused on those with drug-resistant virus. METHODS: We examined
      antiretroviral-treated patients with drug resistance in the Study of the
      Consequences of the Protease Inhibitor Era, a clinic-based cohort of HIV-infected
      adults. Sexual behavior was ascertained by self-administered questionnaire.
      Genotypic antiretroviral resistance testing was performed on isolates from
      participants with a plasma HIV RNA level > or =100 copies/mL. RESULTS: Among 279
      participants on antiretroviral therapy, 168 (60%) had genotypic resistance to at
      least 1 drug. In those with drug resistance, 27% of men who have sex with men
      (MSM) and 11% of heterosexual men and women reported at least 1 episode of
      unprotected penile-anal or penile-vaginal intercourse in the previous 4 months;
      17% of MSM and 6% of heterosexual participants reported unprotected intercourse
      with an HIV-uninfected or status unknown partner. In a multivariable model of
      predictors of unprotected anal or vaginal intercourse with an HIV-uninfected or
      status unknown partner, there was strong evidence for an effect of younger age,
      depression, and sildenafil use and moderate evidence for frequent alcohol use.
      CONCLUSIONS: Among HIV-infected patients with drug-resistant viremia, there is a
      substantial prevalence of high-risk sex with HIV-uninfected partners. The
      presence of definable risk factors for unsafe sex suggests a role for targeted
      rather than broad intervention, particularly when resources are limited.

PMID- 16280704
TI  - The development and utility of a clinical algorithm to predict early HIV-1
      infection.
AB  - The association between self-reported clinical factors and recent HIV-1
      seroconversion was evaluated in a prospective cohort of 4652 high-risk
      participants in the HIV Network for Prevention Trials (HIVNET) Vaccine
      Preparedness Study. Eighty-six individuals seroconverted, with an overall annual
      seroconversion rate of 1.3 per 100 person-years. Four self-reported clinical
      factors were significantly associated with HIV-1 seroconversion in multivariate
      analyses: recent history of chlamydia infection or gonorrhea, recent fever or
      night sweats, belief of recent HIV exposure, and recent illness lasting > or =3
      days. Two scoring systems, based on the presence of either 4 or 11 clinical
      factors, were developed. Sensitivity ranged from 2.3% (with a positive predictive
      value of 12.5%) to 72.1% (with a positive predictive value of 1%). Seroconversion
      rates were directly associated with the number of these clinical factors. The use
      of scoring systems comprised of clinical factors may aid in detecting early and
      acute HIV-1 infection in vaccine and microbicide trials. Organizers can educate
      high-risk trial participants to return for testing during interim visits if they
      develop these clinical factors. Studying individuals during early and acute HIV-1
      infection would allow scientists to investigate the impact of the intervention
      being studied on early transmission or pathogenesis of HIV-1 infection.

PMID- 16280705
TI  - Lower mother-to-child HIV-1 transmission in boys is independent of type of
      delivery and antiretroviral prophylaxis: the Italian Register for HIV Infection
      in Children.
AB  - The relationship between infant's gender and rate of HIV-1 mother-to-child
      transmission (MTCT) was evaluated in a prospective cohort of 4151 children (2166
      boys and 1985 girls) born to HIV-1-infected mothers enrolled in the Italian
      Register for HIV Infection in Children. Logistic regression models were performed
      to estimate crude odds ratios (ORs) and adjusted odds ratios (AORs) and 95% CIs
      for factors potentially influencing MTCT separately for the period 1985-1995 and
      the period 1996-2001. To evaluate rates of MTCT by gender in specific subgroups,
      separate logistic regression models by mode of delivery and antiretroviral
      prophylaxis were performed. Among children born in 1985-1995, 15.5% boys (95% CI:
      13.6-17.7) and 17.9% girls (95% CI: 15.7-20.3) were infected (P = 0.1181). After
      1995, a lower proportion of boys (3.1% [95% CI: 2.0-4.4]; AOR: 0.43 [95% CI: 0.26
      0.71], P = 0.0008) than girls (AOR: 6.3%, 95% CI: 4.8-8.1) was infected. Lower
      AORs for boys persisted independently of elective cesarean delivery (AOR: 0.31,
      95% CI: 0.14-0.71); other than elective cesarean (AOR: 0.38, 95% CI: 0.19-0.78)
      and antiretroviral prophylaxis (zidovudine monotherapy (AOR: 0.11, 95% CI: 0.03
      0.38); none (AOR: 0.43, 95% CI: 0.21-0.90). No difference was observed when
      combined therapy in the mother was administered (AOR: 1.14, 95% CI: 0.30-4.32),
      but results were likely to be biased by the very low rate of infected children in
      this group. A lower proportion of HIV-1-infected boys in children born after 1995
      was found. Factor(s) intrinsic to gender (rather than type of delivery or
      maternal antiretroviral prophylaxis) may be involved, because the risk of
      infection in boys was lower independent of interventions. A possible explanation
      is that, among infected fetuses, more girls survive up to the end of pregnancy
      and may take advantage of the benefits of preventive strategies.

PMID- 16280706
TI  - Integrating prevention of mother-to-child HIV transmission into routine antenatal
      care: the key to program expansion in Cameroon.
AB  - With funds from Elizabeth Glaser Pediatric AIDS Foundation, the Cameroon Baptist
      Convention Health Board implemented a program to prevent mother-to-child
      transmission of HIV-1 (PMTCT) as part of its routine antenatal care, with single
      dose maternal and infant peripartum nevirapine (NVP) prophylaxis of HIV-positive
      mothers and their babies. Nurses, midwives, nurse aides, and trained birth
      attendants counseled pregnant women, obtained risk factor data, and offered free
      HIV testing with same-day results. From February 2000 through December 2004, this
      program rapidly expanded to 115 facilities in 6 of Cameroon's 10 provinces, not
      only to large hospitals but to remote health centers staffed by trained birth
      attendants. We trained 690 health workers in PMTCT and counseled 68,635 women,
      91.9% of whom accepted HIV testing. Of 63,094 women tested, 8.7% were HIV-1
      positive. Independent risk factors for HIV-1 infection included young age at
      first sexual intercourse, multiple sex partners, and positive syphilis serology
      (P < 0.001 for each). We counseled 98.7% of positive and negative mothers on a
      posttest basis. Of 5550 HIV-positive mothers, we counseled 5433 (97.9%) on single
      dose NVP prophylaxis. Consistent training and programmatic support contributed to
      rapid upscaling and high uptake and counseling rates.

PMID- 16280708
TI  - Assessment of adherence to highly active antiretroviral therapy in a cohort of
      African HIV-infected children in Abidjan, Cote d'Ivoire.
AB  - African HIV-infected children benefit from access to antiretroviral treatments
      but little is known about their adherence. A cross-sectional assessment of
      adherence to highly active antiretroviral therapy was conducted among a group of
      children recruited in an observational cohort in Abidjan, Cote d'Ivoire.
      Adherence was determined by a 1-month recall by child or caregiver, with full
      adherence signifying no interruptions in the prior month. One-third reported less
      than full adherence. Undetectable viral load was associated with full adherence
      in a subset of children with a P value <10% (P = 0.098). As compared with
      children with full adherence, those with less than full adherence were
      significantly older and more likely to be taking efavirenz. These findings
      underscore the necessity of assessing and supporting children's adherence
      routinely in AIDS care institutions.

PMID- 16280707
TI  - High maternal HIV-1 viral load during pregnancy is associated with reduced
      placental transfer of measles IgG antibody.
AB  - BACKGROUND: Studies among HIV-1-infected women have demonstrated reduced
      placental transfer of IgG antibodies against measles and other pathogens. As a
      result, infants born to women with HIV-1 infection may not acquire adequate
      passive immunity in utero and this could contribute to high infant morbidity and
      mortality in this vulnerable population. METHODS: To determine factors associated
      with decreased placental transfer of measles IgG, 55 HIV-1-infected pregnant
      women who were enrolled in a Nairobi perinatal HIV-1 transmission study were
      followed. Maternal CD4 count, HIV-1 viral load, and HIV-1-specific gp41 antibody
      concentrations were measured antenatally and at delivery. Measles IgG
      concentrations were assayed in maternal blood and infant cord blood obtained
      during delivery to calculate placental antibody transfer. RESULTS: Among 40 women
      (73%) with positive measles titers, 30 (75%) were found to have abnormally low
      levels of maternofetal IgG transfer (<95%). High maternal HIV-1 viral load at 32
      weeks' gestation and at delivery was associated with reductions in placental
      transfer (P < 0.0001 and P = 0.0056, respectively) and infant measles IgG
      concentrations in cord blood (P < 0.0001 and P = 0.0073, respectively). High
      maternal HIV-1-specific gp41 antibody titer was also highly correlated with both
      decreased placental transfer (P = 0.0080) and decreased infant IgG (P < 0.0001).
      CONCLUSIONS: This is the first study to evaluate the relationship between
      maternal HIV-1 viremia, maternal HIV-1 antibody concentrations, and passive
      immunity among HIV-1-exposed infants. These data support the hypothesis that high
      HIV-1 viral load during the last trimester may impair maternofetal transfer of
      IgG and increases risk of measles and other serious infections among HIV-1
      exposed infants.

PMID- 16280709
TI  - Genetic characterization of full-length HIV type 1 genomes from 3 infected paid
      blood donors in Henan, China.

PMID- 16280710
TI  - Osteoporosis in HIV-infected subjects: a combined effect of highly active
      antiretroviral therapy and HIV itself?

PMID- 16280711
TI  - The effect of limb length discrepancy on health-related quality of life: is the
      '2 cm rule' appropriate?
AB  - The primary goal of surgical equalization of lower extremity limb length
      discrepancy is to enhance the quality of life of patients by improving their
      function, gait, appearance, and pain secondary to compensation for the limb
      length discrepancy. While many surgeons use a cutoff point of 2 cm as an
      indication for intervention, little attention has been given to the effect of
      limb length discrepancy on quality of life. Therefore, the purpose of this study
      was to determine the relationship between limb length discrepancy and health
      related quality of life and to assess whether the commonly accepted 2 cm cutoff
      serves to predict patients with and without quality of life perturbations. The
      Child Health Questionnaire was used to collect information from the parents of 76
      children diagnosed with limb length discrepancy, and these data were compared
      with data from scanograms. Differences in quality of life became more apparent
      with increasing limb length discrepancy, especially among psychosocial health
      domains. As expected, patients with a limb length discrepancy of 2 cm or below
      generally fared better than patients with larger discrepancies, but no discrete
      cutoff could be identified within this group.

PMID- 16280712
TI  - Serial bone scintigraphy in Legg-Calve-Perthes disease: correlation with the
      Catterall and Herring classification.
AB  - Radiographic classifications in Legg-Calve-Perthes disease are difficult to use
      in the early stage of the disease. Changes on bone scintigraphy
      (revascularization versus recanalization pathway) precede the radiographic
      changes. Our purpose was to study the correlation between serial bone
      scintigraphy and radiographic classifications in Legg-Calve-Perthes disease. In
      86 patients, 95 hips that presented with Legg-Calve-Perthes disease in the early
      stage were followed with serial bone scintigraphy and radiographs. Forty-four
      hips showed recanalization: pathway A on bone scintigraphy. Of these hips 96%
      were classified as Herring A or B and 66% as Catterall 2. Thirty-five hips showed
      revascularization: pathway B on bone scintigraphy. Of this group 82.8% were
      classified as Herring C and 17.1% as Herring B. All pathway B hips have Catterall
      3 or 4. Sixteen hips showed pathway C: regression from pathway A to pathway B.
      They presented in 56% of cases with Herring B, 44% with Herring C, and in 81%
      with Catterall 3 or 4 classifications. We can conclude that there is a
      significant correlation between the vascularization pattern and the radiographic
      classification of Herring and Catterall.

PMID- 16280713
TI  - Avascular necrosis of the femoral head in sickle-cell disease: restoration of
      sphericity and congruency following triple pelvic osteotomy. A case report.
AB  - A 9-year-old boy, originally from Zaire, presented with homozygous sickle-cell
      disease and a unilateral avascular necrosis of the femoral head. He was treated
      with a triple pelvic osteotomy to improve containment and stimulate remodelling
      of the head following prior partial reduction in a spica cast. Four and a half
      years postoperatively the patient was pain free with normal hip function.
      Radiography revealed a well-centred hip with a mild coxa magna and a nearly
      spherical femoral head. In geographic regions with a small black population,
      sickle cell disease and related orthopaedic problems are rarely encountered, but
      one must be prepared for the occasional patient. Triple pelvic osteotomy for the
      treatment of femoral head necrosis associated with sickle cell disease has not
      yet been reported and has led in this case to a highly satisfying improvement of
      the hip.

PMID- 16280714
TI  - Perthes' disease in the very young child.
AB  - We report two cases of very young children who presented with irritable hips and
      in whom magnetic resonance imaging with gadolinium-enhancement revealed ischaemic
      changes affecting the capital ossific nucleus. Radiological changes consistent
      with Perthes' disease subsequently appeared. In the published literature Perthes'
      disease has been reported in children as young as 24 months. Gadolinium-enhanced
      magnetic resonance imaging has revealed Perthes' disease in younger children
      which can predate the appearance of radiographic changes by up to 3 months.

PMID- 16280715
TI  - Is concomitant bone surgery necessary at the time of open reduction in
      developmental dislocation of the hip in children 12-18 months old? Comparison of
      open reduction in patients younger than 12 months old and those 12-18 months old.
AB  - It is controversial to perform bone surgery at the time of open reduction in
      developmental dislocation of the hip in children 12-18 months old. The purpose of
      this study is to investigate whether concomitant bone surgery is necessary in
      patients treated with medial open reduction in this age range. Patients that were
      under 12 months of age at the time of open reduction were compared with patients
      that were 12-18 months old. Forty-four hips of 30 patients treated with open
      reduction through Ferguson's medial approach have been included in the study.
      Mean follow-up was 19.6 years (13-27.5). Age at the time of open reduction was
      less than 12 months in 21 hips (group A) and 12 months or more in 23 hips (group
      B). There was no significant difference between two groups concerning avascular
      necrosis or unsatisfactory radiological outcome (Severin's groups III and IV). A
      higher rate of secondary bone surgery was necessary in group B than in group A.
      Although secondary bone surgery is needed at a higher frequency in children 12-18
      months old, the radiological outcome is not significantly different for patients
      younger than 12 months. Therefore, the recommendation of concomitant bone surgery
      on a routine basis during open reduction in developmental dislocation of the hip
      in children 12-18 months old is debatable.

PMID- 16280716
TI  - Alternative reliable techniques in femoral torsion measurement.
AB  - The clinical and conventional bi-planar determinations of femoral torsion were
      compared with the tomographic technique, the reliability of which was confirmed.
      Femoral torsions were measured with the trochanteric prominence angle test, the
      sinus-wave bi-planar conventional radiographic technique, the modified Hermann bi
      planar conventional radiographic technique and the limited three-dimensional
      volumetric tomography technique in 34 femora of 17 patients. There was a strong
      correlation between the modified Hermann and the limited tomography techniques
      for 14 intact and 20 fractured femora. If limited three-dimensional volumetric
      tomography cannot be obtained, the modified Hermann bi-planar conventional
      radiographic technique must be used in patients who have scarring about the
      proximal femur and obesity. Otherwise use of the trochanteric prominence angle
      test is much more cost-effective and is as accurate as the limited three
      dimensional volumetric tomography technique.

PMID- 16280717
TI  - Bensahel et al. and International Clubfoot Study Group evaluation of treated
      clubfoot: assessment of interobserver and intraobserver reliability.
AB  - In order to assess interobserver and intraobserver reliability of an evaluation
      system of the International Clubfoot Study Group, 30 children treated for
      unilateral clubfoot and their radiographs were examined by three different
      observers. The mean intraobserver kappa value was found to be 0.62. The mean
      interobserver kappa value was 0.73. These kappa values correlated with a
      substantial degree of agreement. Interobserver reliability for all subgroup
      evaluations (morphologic, functional and radiological) and total scores was 90%
      or over. This also indicates a good interobserver reliability. In conclusion, the
      Bensahel et al. and International Clubfoot Study Group outcome evaluation system
      may be used reliably for the assessment of outcome of the treatment of clubfoot.

PMID- 16280718
TI  - Carrying angle in children: a normative study.
AB  - Information about the carrying angle and its variations are important in the
      management of paediatric elbow injuries. We measured the carrying angle using
      bony landmarks for 300 rural South Indian children aged 5-18 years. The study
      confirms that the clinical carrying angle correlates best with age up to 15
      years, following which there was a slight decrease in the angles. The rate of
      increase of the carrying angle for boys and girls is 0.42 and 0.60 degrees per
      year respectively. Sex differences seem to gradually increase with a maximum
      being around puberty. The carrying angle is greater in girls than in boys by a
      mean of 1.31 degrees. The carrying angle did not correlate well with height,
      weight, humeral length or ulnar length. The reproducibility of measuring the
      carrying angle by the simple technique used in our study leads us to propose that
      this may be used in actual clinical practice.

PMID- 16280719
TI  - Orthopaedic manifestations and management of spondyloepimetaphyseal dysplasia
      Strudwick type.
AB  - Spondyloepimetaphyseal dysplasia (SEMD) Strudwick type is a rare autosomal
      dominant condition arising from defects in COL2A1 the genes responsible for the
      biosynthesis of procollagen type II. The orthopaedic manifestations of patients
      can be hypoplastic odontoid peg with atlantoaxial instability, severe kyphosis or
      lordosis of dorsal and lumbar spines, hip subluxation, coxa vara and early severe
      hip osteoarthritis, and malalignment of lower limbs like genu valgum or club
      foot. We report a mother and daughter with SEMD Strudwick Type and describe their
      orthopaedic problems, surgical management and clinical outcome after 30 years and
      7 years of follow-up respectively.

PMID- 16280720
TI  - Treatment of severely displaced proximal humeral fractures in children with
      elastic stable intramedullary nailing.
AB  - We report on our 8-year experience of using elastic stable intramedullary nailing
      for severely displaced proximal humeral fractures in children. Fourteen patients
      (mean age 13.4 years) with seven epiphyseal and seven metaphyseal fractures
      underwent intramedullary nailing, using single nail fixation in 12 cases.
      Clinical and radiological healing was achieved at 2.4 and 3.2 months,
      respectively. Complications included temporary shoulder and elbow stiffness in
      one and four cases, respectively, one nail breakage at removal, two cases with
      minor humeral shortening, and two cases with minor varus deformity. At the final
      (14.6-month) follow up all patients had a symptom-free full range of motion.
      Elastic stable intramedullary nailing is a valid method of treating severely
      displaced proximal humeral fractures in children.

PMID- 16280721
TI  - Neurovascular complications and severe displacement in supracondylar humerus
      fractures in children: defensive or offensive strategy?
AB  - Out of 210 children suffering from severely displaced supracondylar fractures, 76
      (36%) presented with immediate neurovascular complications: 47 (22%) were
      neurological, 16 (8%) vascular and 13 (6%) both. Injury to two nerves
      simultaneously was observed in six patients. The median nerve was affected in 28
      cases, the ulnar nerve in 25 and the radial nerve in 13. Posterolateral
      displacement was associated with 86% of damage to the median nerve and 56% of
      damage to the ulnar nerve. Posteromedial displacement was associated with all
      incidents of injury to the radial nerve with one exception. Each patient made
      full neurological recovery, spontaneously and following primary or secondary
      neurolysis performed on nerve injuries in continuity. Two situations of primary
      abolition of the radial pulse were encountered, one involving a pink hand in
      12.5% of cases and the other involving a white hand in 1.5% of cases. There was
      posterolateral displacement in three out of four patients. Postoperative
      vascularization was revealed by immediate return of the radial pulse in 26
      patients and delayed return in three others. Urgent anatomical reduction of the
      fracture and its early fixation are crucial. A conservative therapeutic approach
      is customary in the majority of neurovascular complications. Prognosis is
      generally excellent. Ischaemia of the limb and total ruptures of the nerve are
      very rare.

PMID- 16280722
TI  - Correlation between iatrogenic ulnar nerve injury and angular insertion of the
      medial pin in supracondylar humerus fractures.
AB  - The aim of this study was to assess the correlation between the occurrence of
      iatrogenic ulnar nerve injury and frontal and saggital angular insertion of the
      medial pin in type 3 pediatric supracondylar humerus fractures treated by closed
      reduction and percutaneous fixation using a cross-pin configuration. Radiographs
      of 90 children were retrospectively reviewed and two radiographic parameters were
      measured. The frontal humerus-pin angle was formed between the long axis of the
      humerus shaft and the axis of the medial pin on an anteroposterior radiograph.
      The saggital humerus-pin angle was formed between the long axis of the humerus
      shaft and the axis of the medial pin on a lateral radiograph and expressed as
      positive and negative values if the insertion direction of the pin was anterior
      to posterior or posterior to anterior, respectively. There was a significant
      difference between the mean saggital humerus-pin angle values of ulnar nerve
      injury and no neurological complication groups (12.1 degrees versus 1.6 degrees ,
      respectively; P=0.001). It was concluded that, anteroposterior insertion of the
      medial pin in the saggital plane, while the elbow was in hyperflexion, correlated
      with the occurrence of iatrogenic ulnar nerve injury.

PMID- 16280723
TI  - Pink pulseless hand following supra-condylar fractures: an audit of British
      practice.
AB  - A postal questionnaire was sent to the members of the British Society for
      Children's Orthopaedic Surgery to form a consensus on the management of displaced
      supra-condylar fractures especially when complicated by a 'pink pulseless hand'.
      A majority of the paediatric orthopaedic practitioners in the United Kingdom
      would deal with the uncomplicated supra-condylar fractures as soon as possible
      but not after midnight. In the absence of a radial pulse, stabilization would be
      considered even after midnight. If the hand remains pulseless but well perfused
      after stabilization the preferred option would be to observe and rely on
      collateral circulation rather than treating it more aggressively.

PMID- 16280724
TI  - Partial physeal growth arrest treated by bridge resection and artificial dura
      substitute interposition.
AB  - We treated four cases of partial physeal growth arrest by resecting the bone
      bridge and interposing an expanded polytetrafluoroethylene membrane, which has
      minimal tissue response. We evaluated three cases with sufficiently long follow
      up. No apparent recurrence of the bone bridge and no limb length discrepancy
      occurred in any of the cases. No remodeling after the operation occurred. In one
      case, which underwent this operation and corrective osteotomy of the proximal
      tibia, slight recurrence of the varus deformity occurred which was detected only
      by radiographs, and did not compromise the alignment of the leg. There were no
      complications.

PMID- 16280725
TI  - Ultrasound: a helpful technique in the analysis of congenital vertical talus. A
      case report.
AB  - Congenital vertical talus is a rare condition. In newborns, the diagnosis is
      evident in severe forms, but it can be difficult to confirm in mild ones. Non
      ossified tarsal navicular cannot be visualized on standard roentgenograms until
      it is ossified. This work demonstrates that ultrasound is helpful in the early
      diagnosis of congenital vertical talus and in the evaluation of the therapeutic
      concept and effects.

PMID- 16280726
TI  - Recurrent migratory sympathetically maintained pain syndrome in a child: a case
      report.
AB  - A 10-year-old boy presented with pain and swelling of short duration in his right
      hand. A traumatic cause was ruled out. He had clinical features suggestive of
      sympathetic overactivity in the form of hyperesthesia, edema and dry skin. The
      results of a few baseline investigations performed at this stage were all within
      normal limits. A provisional diagnosis of sympathetically maintained pain
      syndrome (SMPS) was made. He responded dramatically to a stellate ganglion block.
      His symptoms recurred within 3 weeks, though now in the lower limb. Again the
      clinical features were consistent with SMPS. His response to a lumbar sympathetic
      block was again dramatic. This case illustrates that the diagnosis of SMPS is
      essentially clinical and that prompt diagnosis and treatment with sympathetic
      blocks can be very rewarding.

PMID- 16280727
TI  - Tripartite patella: late appearance of a third ossification center in childhood.
AB  - Bilateral radiographic progression of the supero-lateral fragment of a bipartite-
      into a tripartite patella with unilateral symptoms. An 8 year old girl presented
      a bilateral bipartite patella Stage III as an incidental finding after fall on
      the flexed right knee. Serial radiographs two years later revealed a bilateral
      progression of the bipartite- into a tripartite patella with complaints only on
      the post-traumatic right side. Observation was opted as therapy. There was no
      correlation of symptoms and radiological findings of the fragmentation of the
      bipartite- into a tripartite patella. Therefore we conclude the etiology of a
      bilateral late appearance of a third ossification center.

PMID- 16280731
TI  - Stem cells--brave new world?

PMID- 16280732
TI  - Transurethral resection of superficial bladder cancer: technically safe,
      oncologically anything but perfect.

PMID- 16280733
TI  - Ureteral obstruction and stents: still a difficult problem for patients and
      urologists alike.

PMID- 16280734
TI  - Epidermal growth factor and spermatogenesis.

PMID- 16280735
TI  - How to decrease pain during transrectal ultrasound guided prostate biopsy: a look
      at the literature.
AB  - PURPOSE: There is growing interest among urologists on the need for decreasing
      pain during transrectal ultrasound (TRUS) guided prostate biopsy. MATERIALS AND
      METHODS: We performed a systematic MEDLINE search of clinical trials of any kind
      of anesthesia, analgesia or sedation during TRUS guided prostate biopsy published
      since 2000. We critically analyzed the impact of pain and discomfort associated
      with the procedure, the described methods for evaluating it and the different
      techniques that have been described. RESULTS: There is strong evidence in the
      current literature that patient tolerance and comfort during TRUS guided prostate
      biopsy can be improved by anesthesia/analgesia. What remains is the need to urge
      all urologists to introduce it in clinical practice as a routine part of the
      procedure, whatever the biopsy scheme. CONCLUSIONS: Of the various options
      periprostatic anesthetic infiltration has been shown to be safe, easy to perform
      and highly effective. It should be considered the gold standard at the moment,
      even if the optimal technique remains to be established. Further studies
      addressing this issue are warranted.

PMID- 16280736
TI  - The effects of 5alpha-reductase inhibitors on the natural history, detection and
      grading of prostate cancer: current state of knowledge.
AB  - PURPOSE: The Prostate Cancer Prevention Trial (PCPT) showed that the 5alpha
      reductase inhibitor (5ARI) finasteride significantly decreased the 7-year period
      prevalence of prostate cancer vs placebo. However, Gleason score 7-10 tumors were
      significantly more common in the finasteride vs the placebo group. We considered
      data on the effects of 5ARIs on prostate cancer natural history and detection.
      MATERIALS AND METHODS: A detailed review was performed of the literature
      identified from the MEDLINE database examining the effects of 5ARIs on prostate
      cancer prevalence and tumor histopathology. RESULTS: In PCPT there were fewer
      biopsies performed for cause in the finasteride vs the placebo group and the
      proportion of high grade tumors in the treatment groups did not diverge with
      time. Given that finasteride has an effect on prostate specific antigen and
      prostate volume, which are key factors in triggering prostate biopsies, they may
      be significant confounders of Gleason score results. Prostate shrinkage in the
      finasteride treated group may minimize biopsy sampling error. Furthermore,
      histological studies have shown that 5ARIs have a significant effect on prostate
      architecture, which can make the interpretation of prostate specimens in men
      treated with 5ARIs difficult. Further evaluation of PCPT findings will help
      determine the true nature of these observations. CONCLUSIONS: 5ARIs decrease the
      risk of prostate cancer but also alter the detection of disease through effects
      on prostate specific antigen, and prostate volume and histology. The weight of
      evidence suggests an artifactual effect of finasteride on Gleason grading in the
      PCPT. The role of 5ARIs for prostate cancer chemoprevention needs further
      examination before it can be considered for wide recommendation.

PMID- 16280737
TI  - Sexual dysfunction after radical prostatectomy: prevalence, treatments,
      restricted use of treatments and distress.
AB  - PURPOSE: Cancer of the prostate (CAP) is one of the most common malignancies
      affecting North American men with about 215,000 new cases and 35,800 CAP related
      deaths annually. The most prevalent intervention for localized CAP is radical
      prostatectomy (RP) with 10-year survival rates approaching 90%. Studies of men in
      post-RP recovery indicate that 44% to 75% experience sexual dysfunction and more
      than 60% experience distress in reaction to sexual dysfunction problems. These
      findings are increasingly significant as prostate specific antigen testing
      continues to increase CAP detection rates, resulting in more and younger post-RP
      patients confronting sexual dysfunction. MATERIALS AND METHODS: A MEDLINE
      database search was performed for articles published from 1966 to September 2004.
      RESULTS: Despite effectiveness 30% to 50% of patients who turn to sexually
      assistive aids after RP discontinue use within a year. This suggests that the
      achievement of physical responsiveness to an aid is necessary but it is not a
      sufficient factor in long-term sexual adaptation. Current research exploring this
      gap between effectiveness and ongoing use supports a broader perspective of
      sexual dysfunction emphasizing several factors, including perceptions of
      inadequacy, anxieties in regard to performance and depression in each member of
      the couple, overly enthusiastic expectations, partner physical/emotional
      readiness to resume active sex, the meaning to the couple of using a sexual aid
      and the quality of the nonsexual relationship of the couple. CONCLUSIONS: Our
      findings reveal the need to explore broader strategies for improving patient
      coping ability and adaptation. They also point to the need to explore the role of
      resumed satisfying sexuality in overall quality of life following treatment.

PMID- 16280738
TI  - Kidney displacement simulator for retroperitoneal laparoscopic nephrectomy.
AB  - PURPOSE: We evaluated the efficacy of a renal displacement simulator originally
      developed at our department for retroperitoneal laparoscopic nephrectomy.
      MATERIALS AND METHODS: A total of 12 patients with a malignant localized renal
      (7) or ureteral (5) neoplasm underwent multidetector row computerized tomography.
      Imaging data were sent to a dedicated work station to create volume rendering and
      virtual laparoscopic images of the kidney, which was displaced ventral using a
      retroperitoneal balloon. These findings were compared with video images obtained
      during laparoscopy surgery. RESULTS: The kidney displacement simulator depicted
      all renal arteries (100% sensitivity) and 13 of 14 renal veins (93% sensitivity).
      Hilar anatomy, including the tumor, as well as major vessels and their
      relationships were visualized by the simulator in the laparoscopic views. The
      major vessel portions completely corresponded to those seen during surgery, and
      the left adrenal and gonadal veins were also synchronized quite well.
      CONCLUSIONS: Our kidney displacement simulator was able to visualize the major
      vessel portions and branched small vessels, such as the adrenal and gonadal
      veins, prior to surgery. It is considered useful for providing guidance to
      surgeons and decreasing operative risks and possible complications.

PMID- 16280739
TI  - Cystic renal cell carcinomas in adults. Is preoperative recognition of
      multilocular cystic renal cell carcinoma possible?
AB  - PURPOSES: We correlated clinicopathological and imaging features of multilocular
      cystic renal cell carcinoma (MCRCC) to propose preoperative criteria for
      therapeutic modalities. MATERIALS AND METHODS: A total of 24 RCCs with a chiefly
      cystic component were identified from 1993 to 2002. In each case histological
      slides and available imaging studies were retrieved. Two tumor groups were
      defined, namely MCRCC and clear RCC with cystic change (CRCC) by intrinsic growth
      or necrotic degeneration. Radiological correlation using computerized tomography
      and magnetic resonance imaging was performed considering criteria such as an
      expansile nodule, cyst wall thickness and septa. RESULTS: On imaging MCRCC
      presented as a multilocular cystic mass lacking an expansile nodule, and with
      regular thin cyst wall and septa. On pathological study MCRCC presented as
      complex, multilocular cystic carcinoma with septa covered by low nuclear grade
      clear renal tumor cells without a grossly expansile nodule. They were staged pT1
      with a free clinical course. In contrast, CRCC was identified on imaging with an
      expansile nodule (5 mm or greater), thick, irregular cyst wall and septa. On
      pathological study CRCC was characterized by a grossly expansile nodule in the
      septa and/or cyst wall. Nuclear grade and TNM stage were higher in CRCC.
      CONCLUSIONS: Preoperative recognition of MCRCC is possible using strict
      computerized tomography and/or magnetic resonance imaging criteria. The current
      study confirms the low malignant potential of MCRCC. Nephron sparing surgery
      should be proposed when MCRCC is suspected.

PMID- 16280740
TI  - Lymphovascular invasion independently predicts increased disease specific
      survival in patients with transitional cell carcinoma of the upper urinary tract.
AB  - PURPOSE: We investigated the prognostic impact of lymphovascular invasion (LVI)
      and traditional prognostic factors for survival in a large series of patients
      treated surgically for upper tract transitional cell carcinoma (TCC). We also
      developed a prognostic factors-based model for risk stratification of upper tract
      TCC. MATERIALS AND METHODS: We identified a study population of 173 consecutive
      patients treated surgically for upper tract TCC at our institution between 1980
      and 2002. We compared LVI with other pathological features and determined the
      disease specific survival rate. RESULTS: LVI was found in 52 patients (30.1%). As
      tumor grade and pathological stage increased, the incidence of LVI increased
      significantly. LVI was found in 12 of 133 patients (9.0%) without lymph node
      metastasis compared with 40 of 40 patients (100%) with lymph node metastasis.
      Five and 10-year disease specific survival rates were 84.9% and 80.4% in the
      absence of LVI, and 40.2% and 21.1% in the presence of LVI, respectively (p
      <0.001). In multivariate analysis LVI, pathological T stage and tumor grade were
      independent predictors for disease specific survival. The relative risk of death
      could be expressed with the formula, exp(0.729 x tumor grade + 1.659 x
      pathological T stage + 1.160 x LVI). Using this equation the patients were
      stratified into low risk (grade 1 or 2, LVI negative, stage pT2 or lower), high
      risk (any tumor grade, LVI positive, stage pT3 or greater) and intermediate risk
      (all others) groups with significant differences in survival. Five and 10-year
      disease specific survival rates were 93.0% and 89.4% in the low risk group (82
      patients), 66.8% and 62.9% in the intermediate risk group (53 patients), and
      25.6% and 0% in the high risk group (38 patients), respectively. CONCLUSIONS: In
      addition to pathological stage and tumor grade, LVI is an independent prognostic
      factor for disease specific survival in upper tract TCC. Patients in the high
      and/or intermediate risk groups may benefit from integrated therapies with
      surgery and postoperative systemic chemotherapy.

PMID- 16280741
TI  - The management of malignant ureteral obstruction treated with ureteral stents.
AB  - PURPOSE: We developed an algorithm for the management of ureteral obstruction due
      to malignant extrinsic compression. MATERIALS AND METHODS: We retrospectively
      reviewed all ureteral stents placed for noncalculous reasons at our institution
      from January 1, 1990 to January 1, 2004. Further clinical information was
      gathered from 157 patients with malignant extrinsic ureteral compression. Failure
      was defined as recurrent ureteral obstruction or an inability to place stents
      cystoscopically. RESULTS: A total of 157 patients underwent retrograde ureteral
      stent attempt for malignant extrinsic ureteral obstruction. Mean patient age was
      54.7 years (range 23 to 83) and average followup was 13.6 months. Of our patients
      61% were women, and the most common cancer diagnoses were ovarian cancer (in 26),
      lymphoma (17) and cervical cancer (16). A total of 24 patients required immediate
      percutaneous nephrostomy (PCN) referral. There were 32 patients who experienced a
      late failure and required PCN (average 180 days after initial stent), and 83
      patients in our series (52.9%) who experienced 110 major complications. Type of
      cancer did not predict need for PCN. However, when invasion into the bladder was
      noted on cystoscopy, 55.9% (19 of 34, p = 0.008) progressed to PCN referral. A
      total of 77 patients underwent stent replacement on average 2.8 times and with an
      interval of 95 days. CONCLUSIONS: In our series patients with malignant extrinsic
      ureteral compression presenting for ureteral stent(s) experienced a failure rate
      of 35.7% (56 of 157). Invasion at cystoscopy had a significant predictive value
      for progression to PCN. We present an algorithm on the management of extrinsic
      malignant ureteral obstruction.

PMID- 16280742
TI  - Long-term benefit of 5-aminolevulinic acid fluorescence assisted transurethral
      resection of superficial bladder cancer: 5-year results of a prospective
      randomized study.
AB  - PURPOSE: As shown in various studies 5-aminolevulinic acid (ALA) induces
      fluorescence of malignant and dysplastic bladder tissue and increases tumor
      detection rates by about 20%. However, data on the long-term benefits are sparse.
      Thus, the 5-year outcome data of a prospective randomized trial comparing
      patients who initially underwent bladder tumor resection (TUR) under standard
      white light or with ALA induced fluorescence were evaluated. MATERIALS AND
      METHODS: A total of 115 patients with suspected superficial bladder cancer were
      randomized to undergo standard or ALA assisted TUR. After the second look TUR at
      6 weeks patients were followed for a median of 39 (standard) and 42 (ALA) months.
      RESULTS: Median time to first recurrence was 5 months in the standard and 12
      months in the ALA group. Recurrence-free survival was 25% in the standard and 41%
      in the ALA group. The recurrence rate at 2, 12, 36 and 60 months after initial
      TUR was 41%, 61%, 73% and 75%, and 16%, 43%, 59% and 59% in the white light and
      ALA groups, respectively. The total number of recurrences was 82 in the standard
      and 61 in the ALA group. Tumor progression occurred in 9 patients in the standard
      and 4 in the ALA group. Cost analysis suggests a considerable economical
      advantage of ALA fluorescence assisted TUR compared to the standard procedure.
      CONCLUSIONS: The initial advantage of improved tumor detection and decreased
      recurrence rates by ALA fluorescence assisted TUR is maintained for years, and
      effectively reduces morbidity and costs in patients with superficial bladder
      tumors.

PMID- 16280743
TI  - Restaging transurethral resection of high risk superficial bladder cancer
      improves the initial response to bacillus Calmette-Guerin therapy.
AB  - PURPOSE: This study was an evaluation of whether restaging transurethral
      resection (TUR) of superficial bladder cancer improves the early response to
      bacillus Calmette-Guerin (BCG) therapy. MATERIALS AND METHODS: A total of 347
      patients with high risk superficial bladder cancer (high grade Ta and T1 tumors
      associated with carcinoma in situ) underwent a single transurethral resection
      (TUR, 132 patients) or restaging TUR (215 patients) before receiving 6 weekly
      intravesical BCG treatments. The patients were evaluated for response (presence
      or absence of tumor) at first followup cystoscopy, at 6 and 12 months after
      treatment, and evaluated for disease stage progression within 3 years of
      followup. RESULTS: Of the 132 patients who underwent a single TUR before BCG
      therapy, 75 (57%) had residual or recurrent tumor at the first cystoscopy and 45
      (34%) later had progression, compared with 62 of 215 patients (29%) who had
      residual or recurrent tumors and 16 (7%) who had progression after undergoing
      restaging TUR (p = 0.001). CONCLUSIONS: Restaging TUR of high risk superficial
      bladder cancer improves the initial response rate to BCG therapy, reduces the
      frequency of subsequent tumor recurrence and appears to delay early tumor
      progression.

PMID- 16280744
TI  - Uroplakin II as a promising marker for molecular diagnosis of nodal metastases
      from bladder cancer: comparison with cytokeratin 20.
AB  - PURPOSE: Current methods used to determine pathological examination of the
      lymphatics after radical cystectomy are tedious and costly. We performed a
      systemic study of uroplakin II (UP II) and cytokeratin 20 (CK 20) expression in
      pelvic lymph nodes on multiple sides in patients with bladder cancer. MATERIALS
      AND METHODS: A total of 82 pelvic lymph node and 19 bladder tumor samples were
      obtained from 21 patients with bladder cancer by radical cystectomy with pelvic
      lymphadenectomy for reverse transcriptase-polymerase chain reaction assay.
      RESULTS: Of the 19 bladder tumor tissue specimens 19 (100%) and 13 (68.4%) were
      positive for UP II and CK 20 mRNA expression, respectively. UP II mRNA was
      detected in 15 of 16 pelvic lymph node samples (93.8%) with pathologically proven
      metastases, whereas 9 (56.6%) were positive for CK 20 mRNA. The reverse
      transcriptase-polymerase chain reaction assay for UP II was statistically more
      sensitive than that for CK 20 in detecting not only primary tumors, but also
      metastatic pelvic lymph nodes (p = 0.0179 and 0.0373, respectively). Of 66 pelvic
      lymph node samples without metastasis UP II was detected in 6 (10%), while CK 20
      was not. In addition, UP II and CK 20 mRNA could be detected in at least 50 and
      500 bladder cancer HT1197 cells, respectively. CONCLUSIONS: These results
      indicate that UP II might be a more useful marker than CK 20 for detecting
      micrometastases of bladder cancer in the pelvic lymph nodes, although a greater
      number of patients and longer followup are needed to come to a definitive
      conclusion.

PMID- 16280753
TI  - A multicenter clinical trial on the use of (-5, -7) pro prostate specific
      antigen.
AB  - PURPOSE: The determination of pro prostate specific antigen (proPSA) forms has
      been suggested to be promising in prostate cancer diagnosis. In this multicenter
      trial we evaluated the diagnostic usefulness of (-5, -7) proPSA. MATERIALS AND
      METHODS: A total of 2,055 white men, including 1,046 with and 1,009 without
      prostate cancer, with total PSA (tPSA) between 0.28 and 81 ng/ml were
      retrospectively analyzed. Of these men 2,026 and 1,727 had tPSA less than 20 and
      less than 10 ng/ml, respectively. All subjects were untreated for prostatic
      disease and underwent multisector needle biopsy of the prostate. An Elecsys 2010
      analyzer was used to determine tPSA, free PSA (fPSA) and (-5, -7) proPSA in the
      2,055 serum samples. ROC analyses were performed to discriminate men with biopsy
      positive and negative results in the entire and in select tPSA ranges. RESULTS:
      In the select tPSA range 2 to 4 ng/ml the area under the ROC curve for proPSA
      (0.53) and proPSA/fPSA (0.59) was not significantly larger than that for tPSA
      (0.60) or the fPSA/tPSA (f/tPSA) ratio (0.64). In the tPSA range 4 to 10 ng/ml
      the area under the curve for the ratio proPSA/fPSA (0.67) was larger than for
      tPSA (0.53) but not larger than for f/tPSA (0.69). The f/tPSA ratio demonstrated
      the best discriminatory power in this tPSA range of 4 to 10 ng/ml. CONCLUSIONS:
      In this multicenter study no improvement in diagnostic accuracy was shown when
      comparing (-5, -7) proPSA and the corresponding ratios with tPSA or f/tPSA.
      Further studies using other proPSA forms or tumor associated proteins should be
      done.

PMID- 16280754
TI  - Use of 2.6 ng/ml prostate specific antigen prompt for biopsy in men older than 60
      years.
AB  - PURPOSE: Since the United States Food and Drug Administration approved the
      prostate specific antigen (PSA) blood test as an aid to early prostate cancer
      detection, using a cutoff of 4.0 ng/ml in 1994, this cutoff has been widely
      adopted to recommend prostate biopsy. There has been recent investigation into
      lowering the PSA prompt for biopsy, especially in men younger than 60 years. We
      determined how a lower cutoff would perform in men older than 60 years. MATERIALS
      AND METHODS: From a prostate cancer screening study we studied 782 consecutive
      men who underwent prostate biopsy for PSA greater than 2.5 ng/ml or suspicious
      digital rectal examination. Biopsy results were evaluated as a function of
      patient age. RESULTS: Clinical and pathological characteristics of cancers
      detected in the PSA range 2.6 to 4.0 ng/ml were similar regardless of patient
      age. Overall PSA between 2.6 and 4.0 ng/ml was associated with a cancer detection
      rate of 16.2% using a sextant biopsy technique. PSA velocity was similar in men
      with prostate cancer in all age groups. CONCLUSIONS: More than 15% of men with
      PSA 2.6 to 4.0 ng/ml who are 40 years or older have prostate cancer detected with
      sextant needle biopsies. PSA velocity, tumor stage, Gleason grade and tumor
      volume were similar in all age groups.

PMID- 16280755
TI  - Comparison of endorectal magnetic resonance imaging, guided prostate biopsy and
      digital rectal examination in the preoperative anatomical localization of
      prostate cancer.
AB  - PURPOSE: We compared the accuracy of endorectal magnetic resonance imaging
      (erMRI), transrectal ultrasound (TRUS) guided biopsy and digital rectal
      examination (DRE) for detecting the location of cancer in the prostate gland and
      seminal vesicles. MATERIALS AND METHODS: This is a retrospective study of 106
      consecutive patients with prostate cancer who were referred for erMRI before
      radical prostatectomy. Step-section pathological data and erMRI were available in
      90 patients, DRE data were available on 86 and individually labeled sextant core
      biopsies were available in 45. T1 and T2-weighted erMRI was interpreted by a
      single reader, who scored the likelihood of tumor on a 5-point scale in each
      seminal vesicle and in 12 locations in the prostate gland. MR spectroscopy data
      were not used for erMRI interpretation. One pathologist reviewed whole mount
      serial sections of radical prostatectomy specimens. The area under ROC curves was
      used to evaluate accuracy. RESULTS: The area under ROC curves for tumor
      localization was higher for erMRI than for DRE at the prostatic apex (0.72 vs
      0.66), mid gland (0.80 vs 0.69) and base (0.83 vs 0.69). It was likewise higher
      for erMRI than for TRUS biopsy in the mid gland (0.75 vs 0.68) and base (0.81 vs
      0.61) but not in the apex (0.67 vs 0.70). On mixed model analysis erMRI
      significantly increased the accuracy of prostate cancer localization by DRE or
      TRUS biopsy (each p <0.0001). CONCLUSIONS: For prostate cancer localization erMRI
      contributes significant incremental value to DRE or TRUS biopsy findings (each p
      <0.0001).

PMID- 16280756
TI  - The relationship between tumor volume and the number of positive cores in men
      undergoing multisite extended biopsy: implication for expectant management.
AB  - PURPOSE: We assessed the relationship between the number of positive cores
      obtained at extended biopsy and tumor volume in radical prostatectomy specimens
      as a tool for predicting the biological significance of prostate cancer from
      biopsy data. MATERIALS AND METHODS: The study group included 207 men who were
      treated with radical prostatectomy without neoadjuvant therapy at our cancer
      center. All patients were diagnosed by systematic extended biopsy (10 or 11
      cores) performed between 1997 and 2003. The variables analyzed were patient age,
      prostate specific antigen, clinical stage, biopsy Gleason score, maximum tumor
      length in a core, greatest percent of tumor in a core, total tumor length, total
      percent of tumor in all cores, positive core location, initial or repeat biopsy
      and prostate volume in subgroups based on the number of positive cores, that is
      group 1-1, group 2-2 and group 3-3 or more cores. Bivariate correlation analysis
      and multiple logistic regression analysis were used to determine the predictors
      of insignificant cancer. RESULTS: The number of positive cores was significantly
      related to total tumor volume (r = 0.433, p <0.001). Insignificant prostate
      cancer (volume less than 0.5 cc and Gleason score 6 or less) was found in 21.7%
      of patients (45 of 207). The incidence of insignificant cancer was 42.5% (31 of
      73 patients) in group 1, 16.4% (10 of 61) in group 2 and 5.5% (4 of 73) in group
      3. There was a significant difference in the incidence of insignificant cancer
      among the subgroups (group 1 vs 2 p <0.001, group 1 vs 3 p <0.0001 and group 2 vs
      3 p <0.05). The best model for predicting insignificant cancer in group 1 was the
      combination of tumor length less than 2 mm, Gleason score 3 + 4 or less and
      prostate volume greater than 50 cc with 83.9% sensitivity (26 of 31 patients) and
      61.9% specificity (26 of 42). CONCLUSIONS: The probability of insignificant
      cancer was directly related to the number of positive cores. Tumor length in a
      core, Gleason score and prostate volume significantly enhanced the prediction
      model for insignificant cancer in men with 1 positive core who underwent extended
      biopsy.

PMID- 16280757
TI  - Relationship between body size and prostate cancer in a sibling based case
      control study.
AB  - PURPOSE: Body size has been hypothesized to affect the risk of prostate cancer
      (PCa). However, previous studies have provided conflicting results, in that some
      show positive associations, whereas others indicate inverse associations or null
      findings. To further understand this we examined the effects of weight, height,
      body mass index and lean body mass (LBM) on PCa risk and aggressiveness in a
      sibling based case-control study. MATERIALS AND METHODS: A total of 439 cases
      were recruited at major medical institutions in Cleveland, Ohio and Detroit,
      Michigan, and 479 unaffected brothers were recruited as controls. Conditional
      logistic regression with robust variance estimation was used to evaluate the
      association between body size and PCa. RESULTS: Higher LBM was inversely
      associated with PCa, especially in men with more aggressive disease or a later
      age at onset. Comparing those above and below the 25th percentile showed an OR of
      0.49 (95% CI 0.28 to 0.84) and 0.28 (95% CI 0.14, 0.56), respectively. Similar
      inverse patterns were observed for weight. No noteworthy associations were
      observed between PCa and height or body mass index. CONCLUSIONS: These
      observations suggest that PCa may be affected by LBM.

PMID- 16280758
TI  - Serum levels of shed Her2/neu protein in men with prostate cancer correlate with
      disease progression.
AB  - PURPOSE: We determined the association between serum levels of shed Her-2/neu
      protein and disease progression in men with prostate cancer. MATERIALS AND
      METHODS: Serum from 279 patients enrolled in a prospective serum bank and
      database at New York University Medical Center was analyzed using the Food and
      Drug Administration approved Immuno-1 Her-2/neu assay. Patients were classified
      by the Prostate-Specific Antigen Working Group model into 5 groups, namely group
      1-no evidence of cancer in 60, group 2-clinically localized disease in 67, group
      3-prostate specific antigen increasing after therapy and no clinical metastases
      in 77, group 4-clinical metastases and castration sensitivity in 42, and group 5
      clinical metastases and castration resistance in 33. A cutoff of 14 ng/ml for
      normal serum Her-2/neu was established based on the 95th order statistic in group
      1. RESULTS: Of 279 patients 37 (13.3%) had increased serum Her-2/neu, that is 5%,
      11.9%, 10.4%, 16.7% and 33.3% in groups 1 to 5, respectively. There was a
      significant difference between patients with (groups 4 and 5) and without (groups
      2 and 3) clinical metastases (p = 0.006). In group 5 patients serum Her-2/neu was
      significantly higher than in group 2 patients (p <0.02). The risk of cause
      specific death increased significantly with each unit increase in serum Her-2/neu
      (p <0.001). CONCLUSIONS: Increased serum Her-2/neu correlates with the presence
      of metastatic disease and it may indicate an increased risk of death in patients
      with castrate, metastatic prostate cancer. The detection of serum Her-2/neu is a
      minimally invasive alternative to tumor sampling for identifying potential
      candidates for anti-Her-2/neu treatment strategies. Further studies are needed to
      optimize this assay for application in the clinical setting.

PMID- 16280759
TI  - Low serum testosterone levels are associated with positive surgical margins in
      radical retropubic prostatectomy: hypogonadism represents bad prognosis in
      prostate cancer.
AB  - PURPOSE: It has been reported that more aggressive prostate cancer (PC) can be
      associated with low serum testosterone levels. The relationship between serum
      androgens and PC is still not completely understood. In this study we examined
      the association of prognostic factors in men who underwent radical retropubic
      (RRP) prostatectomy with low or normal total testosterone. MATERIALS AND METHODS:
      We retrospectively evaluated 64 consecutive patients with localized PC treated
      with RRP between July 2002 and November 2003. PC was diagnosed by transrectal
      ultrasonography guided biopsy performed for either a suspicious digital rectal
      examination or serum prostate specific antigen greater than 4.0 ng/ml. Gleason
      score was determined in prostatic biopsies. Pathological TNM staging (1997),
      capsular perforation, seminal vesicle involvement and surgical margin status were
      determined in all surgical specimens. The threshold for serum total testosterone
      was 270 ng/dl. In all analyses p <0.05 was considered statistically significant.
      RESULTS: There were no statistically significant differences among prostate
      specific antigen, Gleason score (biopsy or specimen), pathological stage,
      capsular perforation and seminal vesicle involvement. However, patients with low
      total testosterone had increased positive surgical margins (p = 0.026).
      CONCLUSIONS: Patients with low total testosterone more frequently present with
      positive surgical margins in RRP specimens. The true association between low
      testosterone and poor clinical outcome in the long term needs validation in large
      prospective studies.

PMID- 16280760
TI  - Lymphovascular invasion is an independent prognostic factor in prostatic
      adenocarcinoma.
AB  - PURPOSE: Gleason grade and tumor stage are well established prognostic factors in
      prostate cancer. Histological demonstration of tumor in lymphovascular spaces has
      been associated with poor prognosis in many tumor types but it is not included in
      current prostate cancer grading and staging schemes. Whether lymphovascular
      invasion is an independent prognostic factor for disease progression in prostate
      cancer is uncertain. We retrospectively investigated lymphovascular invasion as a
      predictive factor for biochemical failure and cancer specific survival following
      radical prostatectomy. MATERIALS AND METHODS: The records of 504 patients with
      prostatic adenocarcinoma undergoing radical prostatectomy were reviewed for
      lymphovascular invasion. Clinical followup data were available on 459 cases. Mean
      followup was 44 months (range 1.5 to 144). Multivariate analysis was performed
      using the Cox model. RESULTS: Lymphovascular invasion was identified in 106 cases
      (21%). Univariate analysis showed a significant association between
      lymphovascular invasion and higher preoperative serum prostate specific antigen
      (PSA), advanced pathological stage, higher Gleason score, positive surgical
      margins, extraprostatic extension, seminal vesicle invasion, lymph node
      metastasis and perineural invasion (each p <0.001). No association was observed
      between lymphovascular invasion and patient age at surgery, prostate weight or
      high grade prostatic intraepithelial neoplasia. Lymphovascular invasion was an
      independent predictor of PSA recurrence (HR 1.6, 95% CI 1.12 to 2.38, p = 0.01)
      and cancer specific survival (HR 2.75, 95% CI 1.04 to 2.28, p = 0.041) after
      controlling for tumor stage, surgical margins and Gleason grade on multivariate
      analysis. Five-year cancer specific survival was 90% in men with lymphovascular
      invasion compared to 98% in those without lymphovascular invasion (p <0.001).
      CONCLUSIONS: Lymphovascular invasion can be identified in approximately 20% of
      prostate cancer cases. Lymphovascular invasion is an independent risk factor for
      PSA recurrence and cancer death in patients with prostate cancer.

PMID- 16280761
TI  - Cystoprostatectomy for effective palliation of symptomatic bladder invasion by
      prostate cancer.
AB  - PURPOSE: We evaluated the palliative effect of cystoprostatectomy (CP) for
      palliating pelvic symptoms in patients with bladder invasion by prostate cancer.
      MATERIALS AND METHODS: A total of 38 patients with clinical T4 prostate cancer,
      including primary tumors in 17 and recurrence following radiation therapy in 21,
      underwent palliative CP. Local symptoms, the need for surgical procedures to
      relieve obstruction, and chronic tube drainage for urinary obstruction before
      surgery and 3 months after surgery were compared. Average followup was 23 months.
      Time to local and systemic symptom recurrence, biochemical progression and
      metastasis was measured and disease specific survival was determined. RESULTS:
      Local symptoms were reported by 34 patients (89%) before surgery and by 8 (21%)
      after surgery (p = 0.000). Preoperatively a total of 22 tubes were inserted in 13
      patients to overcome urinary obstruction. Average indwelling tube duration was
      6.9 months. A total of 24 transurethral prostatic tumor resections were performed
      in 11 patients. Following CP local symptoms were relieved permanently in 30
      patients. The average interval between surgery and clinical systemic disease was
      26 months. Median time to biochemical progression, metastasis and systemic
      symptoms was 8, 18 and 26 months, respectively. Median disease specific survival
      was 31 months (range 1.7 to 81.2). No perioperative deaths occurred. Rectal
      injuries occurred in 5 cases (13%) during surgery. CONCLUSIONS: Radical CP
      provides effective and durable palliation in patients with locally advanced
      prostate cancer. This procedure can be performed with acceptable morbidity in a
      select group of patients.

PMID- 16280762
TI  - Preoperative prostate specific antigen doubling time and velocity are strong and
      independent predictors of outcomes following radical prostatectomy.
AB  - PURPOSE: Prostate specific antigen (PSA) is a useful marker for predicting
      outcomes following treatment for prostate cancer but, given the evolving nature
      of prostate cancer, there is an ongoing need to refine its use. We assessed
      preoperative PSA doubling time (PSADT) and PSA velocity (PSAV) as predictors of
      outcome following radical retropubic prostatectomy (RRP). MATERIALS AND METHODS:
      We identified 2,290 men who were treated with RRP for prostate cancer between
      1990 and 1999 with multiple preoperative PSA measurements available. PSADT was
      calculated by log linear regression and PSAV was calculated by linear regression.
      These parameters were used in preoperative and postoperative multivariate models
      for the end points of biochemical and clinical progression, and cancer death.
      RESULTS: At a median followup of 7.1 years (range 0.1 to 14.5) biochemical
      progression, clinical progression and death from prostate cancer were observed in
      583, 156 and 42 patients, respectively. The HR for death from prostate cancer was
      6.22 (95% CI 3.33 to 11.61) in men with PSADT less than 18 months vs 18 or
      greater and 6.54 (95% CI 3.51 to 12.19) in men with PSAV greater than 3.4 ng/ml
      yearly vs 3.4 or less. On multivariate analysis adjusting for preoperative or
      postoperative variables PSADT and PSAV remained significant predictors of each
      outcome. When assessed jointly, PSAV was significant as a predictor of
      biochemical progression, while PSADT was a significant predictor of clinical
      progression and cancer death. CONCLUSIONS: This study confirms the usefulness of
      preoperative PSA kinetics for predicting post-RRP outcomes, which may be useful
      for stratifying patients, so that rational management decisions can be made with
      respect to observation, intervention and adjuvant treatment. While PSADT maybe
      biologically more accurate and stronger on multivariate analysis, PSAV is
      clinically easier to use and a good approximation in the short term.

PMID- 16280763
TI  - Gynecomastia and breast pain induced by adjuvant therapy with bicalutamide after
      radical prostatectomy in patients with prostate cancer: the role of tamoxifen and
      radiotherapy.
AB  - PURPOSE: We investigated the role of tamoxifen and radiotherapy (RT) for the
      prevention and treatment of gynecomastia and breast pain during adjuvant
      bicalutamide monotherapy after radical prostatectomy (RP) in patients with
      prostate cancer. Also, we evaluated their effects on patient hormonal status,
      quality of life (QOL), sexual function and prostate specific antigen relapse-free
      survival. MATERIALS AND METHODS: This was a multicenter prospective trial. From
      January 2002 to February 2004, 102 patients who had undergone RP for localized or
      locally advanced prostate cancer were recruited and randomized into 3 groups,
      namely group 1-those receiving only 150 mg bicalutamide as adjuvant hormonal
      therapy, group 2-those receiving bicalutamide and 10 mg tamoxifen, and group 3
      those receiving bicalutamide and RT. Patients in group 1 in whom gynecomastia or
      breast pain developed were subsequently randomized to receive tamoxifen or RT
      soon after symptoms started. Gynecomastia, breast pain, prostate specific
      antigen, QOL, sexual function and hormonal levels were assessed. Minimum followup
      was 12 months. RESULTS: Of group 1 patients 67% had gynecomastia compared with 8%
      in group 2 and 34% in group 3. Breast pain was more frequent in group 1 than in
      groups 2 and 3 (58% vs 7% and 30%, respectively). Differences were significant
      between groups 1 and 2 (OR 0.12 p <0.001), and groups 1 and 3 (OR 0.52 p < 0.01).
      In patients in group 1 who had gynecomastia or breast pain a significant decrease
      in symptoms was achieved in those receiving tamoxifen (p <0.05). Treatments were
      well tolerated in the 3 groups. No differences in QOL between groups 2 and 3 were
      found. At a median followup of 26 months we observed 12 biochemical relapses.
      CONCLUSIONS: Gynecomastia and breast pain induced by bicalutamide monotherapy
      after RP can be prevented and treated. Tamoxifen has been shown to be more
      effective and safe than RT in this setting. QOL and sexual function are not
      negatively influenced by these 2 treatment options.

PMID- 16280764
TI  - Long-term salvage radiotherapy outcome after radical prostatectomy and relapse
      predictors.
AB  - PURPOSE: We assessed the efficacy of salvage radiotherapy (SRT) and analyzed
      predictors of biochemical progression-free survival (bPFS) and distant metastasis
      free survival in patients with clinically localized disease recurrence after
      radical prostatectomy. MATERIALS AND METHODS: The records of 114 patients treated
      with SRT at 2 institutions between 1991 and 2001 were retrospectively reviewed.
      Time to biochemical recurrence and to distant metastases was analyzed using the
      Kaplan-Meier estimation. Candidate predictors of bPFS and distant metastasis-free
      survival were analyzed using the log rank test and Cox regression. Acute and late
      complications were scored using Radiation Therapy Oncology Group/European
      Organization for Research and Treatment of Cancer criteria. RESULTS: At a median
      followup of 6.3 years (range 1.9 to 13.3) for SRT 4 and 6-year bPFS was 50% (95%
      CI 42% to 61%) and 33% (95% CI 24% to 43%), respectively. The 6-year actuarial
      probability of distant metastases after SRT was 14%. Multivariate analysis
      demonstrated an independent association of increasing Gleason score,
      lymphovascular invasion and lack of a complete response to SRT with decreased 5
      year bDFS. These factors were associated with significantly less 5-year distant
      metastasis-free survival. Pre-RT prostate specific antigen greater than 2.0 ng/ml
      was associated with significantly decreased 5-year bDFS and distant metastasis
      free survival, although it was not maintained on multivariate analysis.
      CONCLUSIONS: SRT results in durable prostate specific antigen control in select
      patients. It is well tolerated with few severe late effects. Increasing Gleason
      score, lymphovascular invasion and lack of a complete response to SRT are
      significant risks for disease progression requiring additional management.

PMID- 16280765
TI  - Minimizing treatment without compromising cure with primary surveillance for
      clinical stage I embryonal predominant nonseminomatous testicular cancer: a
      population based analysis from British Columbia.
AB  - PURPOSE: We evaluated the outcome of patients with embryonal carcinoma
      predominant (ECP) clinical stage (CS) I nonseminomatous testicular germ cell
      tumors (NSGCT) treated with primary surveillance or primary retroperitoneal lymph
      node dissection (RPLND). MATERIALS AND METHODS: This study was a retrospective
      evaluation of the pathology, use of chemotherapy, surgery and outcomes in all
      patients with CS I NSGCT who were diagnosed within the province of British
      Columbia between 1990 and 2000. RESULTS: A total of 205 patients were identified,
      of whom 107 (52%) had ECP disease. Of these patients 72 (67%) underwent primary
      surveillance, 32 (33%) underwent primary RPLND and 3 refused treatment. Median
      followup was 4 years (range 1 to 10). In the primary surveillance group 24
      patients (33%) had relapse and all were treated initially with chemotherapy with
      6 also requiring RPLND. The remaining 48 patients (67%) in the surveillance group
      were cured of disease with orchiectomy alone. In the primary RPLND group 18
      patients (56%) had pathological stage I disease and 14 (44%) had pathological
      stage II disease. In the primary RPLND group 15 patients (46%) required
      chemotherapy with 11 (34%) receiving adjuvant chemotherapy and 4 receiving
      chemotherapy for post-RPLND relapse. No deaths from ECP testicular cancer
      occurred in either group. The 4-year chemotherapy-free survival rate was 65% in
      the surveillance group vs 50% in the RPLND group (p = 0.2). CONCLUSIONS: For
      appropriately selected patients with CS I ECP NSGCT, primary surveillance results
      in fewer therapeutic interventions compared to RPLND without compromising the
      probability of cure.

PMID- 16280766
TI  - Reproducibility of lymphoscintigraphy for lymphatic mapping in patients with
      penile carcinoma.
AB  - PURPOSE: We evaluated the reproducibility of lymphoscintigraphy in the assessment
      of the location and number of sentinel nodes in patients with penile carcinoma.
      MATERIALS AND METHODS: A total of 20 patients were prospectively included in
      analysis. Lymphoscintigraphy was performed after intradermal injection of
      technetium nanocolloid around the tumor or excision scar. We performed 10-minute
      anterior dynamic imaging, and static anterior and lateral images were obtained at
      30 minutes and 2 hours. The following day scintigraphy was repeated after a
      second injection of the radiolabeled colloid given in an identical fashion,
      preceded by acquisition of a starting image. An observer evaluated the paired
      images and count rates were calculated from the images. RESULTS: At least 1
      sentinel node was visualized in all patients on the first lymphoscintigram. A
      total of 56 sentinel nodes were seen in 38 basins. Drainage to both groins was
      seen in 18 patients. In 1 of these patients drainage to the prepubic area was
      also observed. There were 2 patients with drainage to 1 groin. The second
      lymphoscintigram revealed the same drainage pattern in all patients- the same
      number of nodal basins and number of sentinel nodes were visualized at identical
      locations. All hotspots that were visualized during the first lymphoscintigram
      showed an unequivocal increase in radioactivity after repeat injection. Thus, the
      reproducibility of penile lymphoscintigraphy was 100% (95% CI 85%-100%). The
      Pearson correlation coefficient of the paired count rates was 0.69 (p <0.0001).
      CONCLUSIONS: Results of lymphoscintigraphy in patients with penile carcinoma are
      highly reproducible for assessment of the number and location of sentinel nodes.

PMID- 16280767
TI  - Phallic preserving surgery in patients with invasive squamous cell carcinoma of
      the penis.
AB  - PURPOSE: Standard surgical methods to eradicate invasive squamous cell carcinoma
      of the penis often result in significant deformities. Wide local excision with
      skin grafting in select cases results in the preservation of normal phallic
      appearance and function. MATERIALS AND METHODS: Seven patients with invasive
      squamous cell carcinoma of the penis were treated with wide excision and
      resurfaced by 1 of 3 methods, namely 1) a split-thickness graft, 2) a full
      thickness graft or 3) shaft skin advancement. RESULTS: At 1 to 5 years of
      followup there was 1 local recurrence proximal to the original resection site.
      Local excision of recurrence resulted in no evidence of disease at 2 years of
      followup following repeat excision. All other patients had no local recurrence.
      CONCLUSIONS: In select cases wide local excision with grafting or skin
      advancement results in a normal phallic appearance without jeopardizing cancer
      control.

PMID- 16280775
TI  - Wound complications after hand assisted laparoscopic surgery.
AB  - PURPOSE: Hand assisted laparoscopic surgery (HALS) provides benefits similar to
      standard laparoscopy but generally requires a larger incision. We assessed the
      nature of and risk factors for incisional complications after HALS. MATERIALS AND
      METHODS: All patients who underwent HALS at our institution from February 1997
      through December 2003 were included in a prospective and retrospective review to
      assess postoperative wound complications. Literature regarding wound
      complications associated with open surgery and standard laparoscopy was reviewed.
      RESULTS: A total of 424 consecutive procedures performed on 422 patients were
      evaluated. Postoperative HALS incision site complications included 29 infections
      (6.8%), 15 hernias (3.5%) and 2 dehiscences (0.5%). Multivariate logistic
      regression models revealed that HALS incision site hernias were associated with
      current or past tobacco smoking (6.0%, p = 0.04), with a trend toward
      significance for diabetes mellitus (14%, p = 0.07), male gender (5.3%, p = 0.08)
      and renal failure (16%, p = 0.08). HALS incision site infections were associated
      with omission of perioperative antibiotics (13%, p = 0.007), obesity (12%, p =
      0.03) and increased operative time (252 vs 222 minutes in patients with and
      without infection, respectively, p = 0.001). CONCLUSIONS: Our findings suggest
      that wound infections and hernias occur less frequently with HALS than with open
      surgery, but more often than with standard laparoscopy. Certain patient
      comorbidities (eg obesity), modifiable risk factors (eg smoking status) and
      procedural variables (eg omission of perioperative antibiotics or length of
      procedure) may adversely influence HALS wound complications. This information can
      be used to decide between HALS and standard laparoscopic approaches in particular
      patients.

PMID- 16280776
TI  - Prevalence of interstitial cystitis symptoms in women: a population based study
      in the primary care office.
AB  - PURPOSE: We estimated the prevalence of urinary symptoms related to interstitial
      cystitis (IC) in women in a primary care practice and confirmed in the United
      States the results of a Finnish population based prevalence study. MATERIALS AND
      METHODS: Every female patient presenting to our office for a routine office visit
      between January 9, 2004 and September 24, 2004 was evaluated for urinary symptoms
      using 2 validated surveys, namely the O'Leary-Sant (OLS) IC symptom and problem
      index, and the Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale.
      RESULTS: Of the 1,218 women in the study group 13 (1.1%) reported severe symptoms
      and problems (12 or greater on the OLS survey), including 7 (0.6%) who met
      previously established criteria for probable IC. In the same population scores on
      the PUF questionnaire indicated that 154 women (12.6%) likely had IC.
      CONCLUSIONS: Based on previously published criteria for use of the OLS survey the
      prevalence of urinary symptoms corresponding to probable IC in our study
      population (575/100,000 or 0.57%, 95% CI 150 to 1,000) was similar to the 0.45%
      rate previously reported. However, the results of the PUF questionnaire indicated
      that the prevalence of IC in women may actually be much higher (12,600/100,000 or
      12.6%, 95% CI 10,700 to 14,500). We suggest that the true prevalence of IC in
      women may be somewhere between these 2 extremes. Further investigation of these
      questionnaires as screening tools for IC is warranted. IC may be more common in
      women than previously reported.

PMID- 16280777
TI  - Cyclosporine A and pentosan polysulfate sodium for the treatment of interstitial
      cystitis: a randomized comparative study.
AB  - PURPOSE: In a previous retrospective analysis, cyclosporine A (CyA) was highly
      efficient in treating patients with interstitial cystitis. A prospective
      randomized study with this immunosuppressive agent was warranted. We compared CyA
      to pentosan polysulfate sodium (PPS) in patients with interstitial cystitis.
      MATERIALS AND METHODS: A total of 64 patients with interstitial cystitis meeting
      the National Institute of Diabetes and Digestive and Kidney Diseases criteria
      were enrolled in a randomized prospective study. Patients were randomized in a
      1:1 ratio to 1.5 mg/kg CyA twice daily (27 women, 5 men) or 100 mg PPS 3 times
      daily (26 women, 6 men) for a period of 6 months. The primary end point was daily
      micturition frequency, and secondary end points were mean and maximal voided
      volume, number of nocturia episodes, O'Leary-Sant symptom and problem indexes,
      visual analogue scale for pain, and subjective global response assessment.
      RESULTS: CyA was superior to PPS in all clinical outcome parameters measured at 6
      months. Micturition frequency in 24 hours was significantly reduced in the CyA
      arm compared to the PPS arm (-6.7 +/- 4.7 vs -2.0 +/- 5.1 times). The clinical
      response rate (according to global response assessment) was 75% for CyA compared
      to 19% for PPS (p <0.001). Although there were more adverse events in the CyA arm
      than in the PPS arm, 29 patients completed the 6-month followup in both groups.
      CONCLUSIONS: CyA is more effective than PPS in interstitial cystitis.

PMID- 16280778
TI  - Cyanoacrylic glue: a minimally invasive nonsurgical first line approach for the
      treatment of some urinary fistulas.
AB  - PURPOSE: We evaluated the adaptability and the efficacy of a cyanoacrylic glue
      for the conservative treatment of urinary fistulas of different etiologies using
      an endoscopic, percutaneous or endovaginal approach. MATERIALS AND METHODS: From
      May 1998 to July 2004, 13 patients with long lasting iatrogenic and/or
      inflammatory urinary fistulas were treated conservatively with endoscopic,
      percutaneous or endovaginal application of 1 to 3 cc of cyanoacrylic glue.
      RESULTS: The complication rate in this cohort of 13 patients was low. Occlusion
      therapy failed in 2 genitourinary fistulas which were wider (diameter greater
      than 1 cm) and short. In the remaining 11 cases urinary fistulas were
      successfully sealed and at a median followup of 35 months no relapses were
      observed. CONCLUSIONS: Cyanoacrylic glue is suitable for endoscopic, percutaneous
      and endovaginal use. This occlusion therapy represents a safe and minimally
      invasive approach that might be offered as a first line option for the treatment
      of urinary fistulas, especially narrow and long tract fistulas.

PMID- 16280789
TI  - Urological intervention in patients with cystinuria is decreased with medical
      compliance.
AB  - PURPOSE: Theoretically patients with cystinuria compliant with medical treatment
      should undergo fewer surgical procedures than those noncompliant with treatment.
      We describe a single urologist's experience (SYN) with the effects of medical
      management on the number of surgical interventions required in patients with
      cystinuria treated at our metabolic stone clinic (MSC). MATERIALS AND METHODS:
      The records of 20 patients with cystine stones seen at our MSC (mean followup of
      42.5 months) were evaluated. The number of surgical interventions (endourology or
      open surgery) during followup were recorded as surgical events. Patients were
      placed into a compliant or noncompliant category based on their attendance record
      at scheduled appointments at our MSC and whether they adhered to the prescribed
      medical regimen by report. Patients were classified in an active disease category
      if recent imaging revealed a clinically significant stone burden greater than 3
      mm. Statistical analysis of the number of surgical events for stone-free patients
      compliant with treatment versus noncompliant was conducted (Student's t test).
      RESULTS: Of the 20 patients 11 were categorized as compliant and 9 as
      noncompliant. Of the compliant patients the average number of surgical events was
      1.0 per patient versus 4.0 in the noncompliant group (p <0.05). Of the 11
      compliant patients 8 (73%) were stone-free compared to 3 (33%) in the
      noncompliant group. CONCLUSIONS: The majority of our patients with cystinuria
      compliant with treatment underwent a significantly fewer number of surgical
      procedures per year than those noncompliant with treatment. Active medical
      management in patients with cystinuria compliant with treatment decreases the
      incidence of surgical interventions.

PMID- 16280793
TI  - Renal artery pseudoaneurysm following laparoscopic partial nephrectomy.
AB  - PURPOSE: We describe the presentation, evaluation and management of hemorrhage
      due to renal artery pseudoaneurysm following laparoscopic partial nephrectomy.
      MATERIALS AND METHODS: Of the 345 laparoscopic partial nephrectomies performed by
      us during a 5-year period 6 patients (1.7%) had postoperative hemorrhage from a
      renal artery pseudoaneurysm. Patient charts were reviewed to identify pertinent
      preoperative, intraoperative and postoperative data. RESULTS: Median tumor size
      was 3.5 cm (range 2.2 to 5), intraoperative blood loss was 175 cc (range 50 to
      500), warm ischemia time was 32 minutes (range 30 to 45) and operative time was
      3.8 hours (range 2.5 to 5). The mean percent of kidney excised was 31% and
      pelvicaliceal system entry was suture repaired in all 6 patients. No patient
      required blood transfusion perioperatively. Average hospital stay was 3.4 days
      (range 2.5 to 6). Delayed postoperative hemorrhage occurred at a median of 12
      days (range 8 to 15). Angiography revealed a renal artery pseudoaneurysm most
      commonly at a third or fourth order branch (4 and 2 patients, respectively).
      Percutaneous embolization was successful in each patient. CONCLUSIONS: Renal
      artery pseudoaneurysm is an uncommon complication following laparoscopic partial
      nephrectomy. These patients often present in delayed fashion. Selective
      angiographic embolization is the initial treatment of choice.

PMID- 16280794
TI  - The actual incidence of bladder perforation following transurethral bladder
      surgery.
AB  - PURPOSE: In this prospective study we evaluated the incidence of bladder
      perforation after transurethral bladder tumor resection. MATERIALS AND METHODS: A
      total of 36 patients (33 male, 3 female, mean age +/- SD 65.6 +/- 11.43 [range 26
      to 81]) with a solid mass in the bladder (mean 20.3 +/- 8.7 mm, range 5 to 40)
      were included in the study. Transurethral resections were performed with a 24Fr
      resectoscope. After the procedure an 18Fr Foley catheter was inserted into the
      bladder and 400 ml of 1/4 saline diluted contrast solution was instilled under
      gravity from 60 cm above the bladder. Complete filling and post-drainage
      radiographs were taken and examined for any evidence of extravasation. Regular
      evaluations with cystoscopy and ultrasound/computerized tomography were done to
      detect possible tumor recurrence and perivesical seeding. RESULTS:
      Histopathological examination of the tumors showed transitional cell carcinoma in
      35 patients and chronic eosinophilic cystitis in 1. Review of the cystograms
      revealed various degrees of extraperitoneal contrast extravasation around the
      resected area in 21 patients (58.3%). The only statistically significant
      difference between patients with and without extravasation was in tumor size
      (logistic stepwise regression p = 0.030,) among factors tested including patient
      age and localization, number of foci, tumor grade and stage. No apparent clinical
      problems requiring medical or surgical intervention other than urethral
      catheterization developed and no evidence of extravesical tumor seeding as per
      ultrasound and/or computerized tomography was seen during a mean followup of 21.9
      months (range 7 to 40). CONCLUSIONS: The extravasation of urine (asymptomatic
      perforation) after transurethral bladder tumor resection may occur much more
      frequently than believed or reported. It seems that this extravasation does not
      impose a significant risk of extravesical tumor seeding.

PMID- 16280802
TI  - Changes in brain activity following sacral neuromodulation for urinary retention.
AB  - PURPOSE: Sacral nerve stimulation (neuromodulation) can restore bladder sensation
      and the ability to void in women with urinary retention due to sphincter
      overactivity (Fowler's syndrome). Modulation of central afferent activity is
      considered critical to this therapeutic effect but the neural mechanisms are
      poorly understood. Therefore, we undertook a functional brain imaging study to
      determine how neuromodulation acts on brain centers involved in the
      representation and control of bladder function. MATERIALS AND METHODS: Eight
      patients with Fowler's syndrome and 8 healthy controls underwent brain imaging
      with positron emission tomography to identify regions of brain activity relating
      to the perception of bladder fullness and their modulation by sacral nerve
      stimulation. RESULTS: In healthy controls bladder fullness enhanced activity in
      brainstem (midbrain) and limbic cortical regions. Women with urinary retention
      showed no significant brainstem activity but did show enhanced limbic cortical
      activity when the bladder was full in the absence of neuromodulation.
      Neuromodulation restored a normal pattern of midbrain activity and decreased
      cortical activity in this group. CONCLUSIONS: Our study provides novel
      neuroimaging evidence for the existence of abnormal interaction between brainstem
      and cortical centers in women with urinary retention. Furthermore, we have been
      able to show evidence that the therapeutic effect of sacral neuromodulation is
      achieved through restoration of activity associated with brainstem autoregulation
      and attenuation of cingulate activity.

PMID- 16280803
TI  - Tolterodine extended release attenuates lower urinary tract symptoms in men with
      benign prostatic hyperplasia.
AB  - PURPOSE: In this open label, prospective study we determined the efficacy and
      tolerability of tolterodine extended release (ER) in men with benign prostatic
      hyperplasia (BPH) and lower urinary tract symptoms (LUTS) in whom previous alpha
      blocker therapy had failed. MATERIALS AND METHODS: A total of 43 consecutive men
      with BPH and LUTS in whom a mean of 5.7 months of alpha-blocker therapy had
      failed due to adverse events (11) or a lack of efficacy (32) received tolterodine
      ER (4 mg daily) for 6 months. Primary efficacy end points were American
      Urological Association symptom score, and mean daytime and nighttime micturition
      frequency. Secondary end points were the peak urinary flow rate, post-void
      residual volume, the incidence of urinary retention, total score on the erectile
      function domain of the International Index of Erectile Function and adverse
      events. RESULTS: A total of 39 men (91%) with a mean age of 61 years completed
      the 6-month trial. Mean 24-hour micturition frequency decreased from 9.8 to 6.3
      voids and nocturia decreased from 4.1 to 2.9 episodes nightly. Significant
      changes in mean American Urological Association symptom scores (-6.1), the peak
      urinary flow rate (1.9 ml per second) and post-void residual volume (-22 ml) were
      also observed. Of the men 27 (63%) were potent at baseline and 29 (67%) were
      potent after 6 months of tolterodine ER treatment. Mean International Index of
      Erectile Function erectile function domain scores increased (6.9). Four men (9%)
      discontinued therapy because of intolerable dry mouth. There were no reports of
      urinary retention. CONCLUSIONS: Treatment with tolterodine ER in men with BPH and
      LUTS may be a reasonable therapeutic option as initial therapy or after failed
      treatment with alpha-blockers.

PMID- 16280813
TI  - End stage polycystic kidney disease: indications and timing of native nephrectomy
      relative to kidney transplantation.
AB  - PURPOSE: We evaluated the indications for and outcome of pre-transplant,
      concomitant and post-transplant native nephrectomy in patients with end stage
      polycystic kidney disease (PCKD). MATERIALS AND METHODS: The records of 32
      patients were retrospectively reviewed using the electronic database at our
      institution. RESULTS: Between January 1992 and December 2002, 171 patients with
      end stage PCKD received a kidney transplant at University of California-San
      Francisco. A total of 32 patients (18.7%) underwent pre-transplant (7, group 1),
      concomitant (16, group 2) or post-transplant (9, group 3) native nephrectomy. Of
      these patients 25 underwent bilateral nephrectomy. Median followup was 18 months.
      Indications for nephrectomy were hematuria, a renal mass and chronic pain in
      group 1, lack of space in group 2 and urinary tract infection in group 3. Mean
      operative time +/- SEM was 231 +/- 14, 370 +/- 24 and 208 +/- 14 minutes in
      groups 1 to 3, respectively (p = 0.001). Mean intraoperative blood loss was 533
      +/- 105, 573 +/- 155 and 522 +/- 181 ml in groups 1 to 3, respectively (p not
      significant). Two group 2 patients required blood transfusions. Postoperative
      complications requiring surgical intervention included wound dehiscence in group
      1 and abdominal bleeding in group 3. Mean hospital stay was comparable among
      groups 1 to 3 at 7 +/- 0.7, 8.6 +/- 1.2 and 6.3 +/- 0.6 days, respectively (p not
      significant). At 3 months mean serum creatinine was not significantly different
      between groups 2 and 3 at 1.3 +/- 0.1 and 1.5 +/- 0.2 mg/dl, respectively.
      CONCLUSIONS: Unilateral or bilateral nephrectomy for PCKD at transplantation is
      safe in terms of postoperative patient morbidity and graft function. We perform
      concomitant native nephrectomy when indicated, preferably in recipients of living
      donor kidney transplants.

PMID- 16280816
TI  - Potency following robotic radical prostatectomy: a questionnaire based analysis
      of outcomes after conventional nerve sparing and prostatic fascia sparing
      techniques.
AB  - PURPOSE: Anatomical nerve sparing radical prostatectomy provides excellent cancer
      control, although the recovery of sexual function is variable. We recently
      described a technique to preserve the prostatic fascia (veil of Aphrodite) that
      appears to enhance the quality of nerve preservation during robotic
      prostatectomy. In January 2003 we initiated a prospective study comparing
      patients undergoing prostatic fascia preservation with those undergoing
      conventional nerve sparing robotic radical prostatectomy. We report results at 12
      months of followup MATERIALS AND METHODS: From January to August 2003, 58 potent
      men with a Sexual Health Inventory for Men score (SHIM) of greater than 21
      without phosphodiesterase 5 inhibitors underwent Vattikuti Institute
      prostatectomy, including 35 with preservation of the prostatic fascia (study) and
      23 with conventional nerve sparing (control). Potency was assessed with self
      administered SHIM questionnaires 12 months after surgery. The primary end point
      was achievement of erections strong enough for penetration with or without oral
      medications. The secondary end point was the ability to achieve normal erections
      (SHIM greater than 21) with and without medications. RESULTS: At 12 months of
      followup 17 of 23 control (74%) and 34 of 35 study (97%) patients achieved
      erections strong enough for intercourse (p = 0.002). Four control (17%) and 18
      study (51%) patients achieved normal erections (SHIM greater than 21) without
      medication (p <0.0001). Six control (26%) and 30 study (86%) patients achieved
      normal erections with or without phosphodiesterase 5 inhibitors (p <0.0001).
      CONCLUSIONS: Potency rates after radical prostatectomy vary with the measure used
      to define potency. Irrespective of the definition used patients undergoing
      prostatic fascia preserving radical prostatectomy have significantly better
      potency outcomes than patients undergoing conventional nerve sparing robotic
      prostatectomy at 12 months of followup.

PMID- 16280829
TI  - A prospective randomized single-blind comparison of ureteral stents composed of
      firm and soft polymer.
AB  - PURPOSE: Ureteral stents are composed of different polymers and it is unclear if
      stent composition influences patient comfort. We compared the impact of stents
      composed of firm and soft polymer on patient health related quality of life.
      MATERIALS AND METHODS: A total of 130 patients requiring insertion of ureteral
      stents during the treatment of urinary calculi were randomized to receive a stent
      composed of firm (Percuflex, group 1) or soft (Contour, group 2) polymer.
      Patients were asked to complete the Ureteric Stent Symptoms Questionnaire, a
      validated instrument, at weeks 1 and 4 with the stent in situ and 4 weeks after
      its removal, this served as the main outcome measure. Additional assessments
      included difficulty in stent insertion and the need for early stent removal.
      RESULTS: There were 78 men and 38 women in total (61 in group 1 and 55 in group
      2) with a mean age of 51 years (range 22 to 79) and no difference in age between
      the 2 groups (p = 0.9). Comparison of the results of the Ureteric Stent Symptoms
      Questionnaire survey at weeks 1 and 4 with stent in situ revealed no significant
      differences in the domain scores of urinary symptoms (p = 0.9 and p = 0.8), pain
      (p = 0.8 and p = 0.6) and general health (p = 0.6 and p = 0.4). Similarly, there
      were no differences in the number of days with reduced activities, work
      performance (p = 0.7) and sexual dysfunction between the 2 groups. A similar
      number of patients (8 and 7 in groups 1 and 2, respectively) required stent
      removal earlier than planned due to stent related symptoms. CONCLUSIONS: This
      randomized study showed no difference in the impact on patient quality of life
      between ureteral stents composed of firm or soft polymer.

PMID- 16280830
TI  - Transurethral bladder tumor resection: intraoperative and postoperative
      complications in a residency setting.
AB  - PURPOSE: We established a database on the incidence of intraoperative and
      postoperative complications associated with transurethral bladder tumor resection
      (TURBT) in an academic teaching setting, and we prospectively recorded all TURBTs
      performed by residents and fellows in our urology department. MATERIALS AND
      METHODS: : We prospectively evaluated all TURBTs performed between November 2003
      and October 2004. All cases were performed at least in part by residents and
      fellows under direct attending supervision at a single academic medical center
      with 3 different teaching hospitals. Intraoperative complications were recorded
      by the resident and attending surgeon at the completion of the operative
      procedure. At patient discharge from the hospital the data sheet was reviewed,
      and length of stay, postoperative transfusions and any other complications were
      recorded. RESULTS: A total of 173 consecutive TURBTs were performed by residents
      and fellows at 3 different teaching hospitals. There were 10 (5.8%)
      complications, including 4 (2.3%) cases of hematuria that required blood
      transfusion and 6 (3.5%) cases of bladder perforation. Of these 6 perforations 4
      were small extraperitoneal perforations requiring only prolonged catheter
      drainage. These perforations were caused by residents in their first or third
      year of urology training. Two perforations were intraperitoneal, caused by a
      senior resident or a fellow, 1 of which required abdominal exploration to control
      bleeding. CONCLUSIONS: TURBT is a reasonably safe procedure when performed by
      urologists in training under direct attending supervision. The complication rate
      was 5.8%, however only 1 case required surgical intervention. Contrary to
      expected findings, more senior residents were involved in the complications,
      likely secondary to their disproportionate roles in more difficult resections.

PMID- 16280831
TI  - A novel computer based expert decision making model for prostate cancer disease
      management.
AB  - PURPOSE: We propose a strategic, computer based, prostate cancer decision making
      model based on the analytic hierarchy process. We developed a model that improves
      physician-patient joint decision making and enhances the treatment selection
      process by making this critical decision rational and evidence based. MATERIALS
      AND METHODS: Two groups (patient and physician-expert) completed a clinical study
      comparing an initial disease management choice with the highest ranked option
      generated by the computer model. Participants made pairwise comparisons to derive
      priorities for the objectives and subobjectives related to the disease management
      decision. The weighted comparisons were then applied to treatment options to
      yield prioritized rank lists that reflect the likelihood that a given alternative
      will achieve the participant treatment goal. Aggregate data were evaluated by
      inconsistency ratio analysis and sensitivity analysis, which assessed the
      influence of individual objectives and subobjectives on the final rank list of
      treatment options. RESULTS: Inconsistency ratios less than 0.05 were reliably
      generated, indicating that judgments made within the model were mathematically
      rational. The aggregate prioritized list of treatment options was tabulated for
      the patient and physician groups with similar outcomes for the 2 groups. Analysis
      of the major defining objectives in the treatment selection decision demonstrated
      the same rank order for the patient and physician groups with cure, survival and
      quality of life being more important than controlling cancer, preventing major
      complications of treatment, preventing blood transfusion complications and
      limiting treatment cost. Analysis of subobjectives, including quality of life and
      sexual dysfunction, produced similar priority rankings for the patient and
      physician groups. Concordance between initial treatment choice and the highest
      weighted model option differed between the groups with the patient group having
      59% concordance and the physician group having only 42% concordance. CONCLUSIONS:
      This study successfully validated the usefulness of a computer based prostate
      cancer management decision making model to produce individualized, rational,
      clinically appropriate disease management decisions without physician bias.

PMID- 16280832
TI  - Incidence and clinical characteristics of National Institutes of Health type III
      prostatitis in the community.
AB  - PURPOSE: Few population-based epidemiological studies of prostatitis have been
      performed. We used coded physician diagnoses and subsequent chart reviews to
      estimate the incidence and clinical characteristics of physician diagnosed
      National Institutes of Health (NIH) type III prostatitis. MATERIALS AND METHODS:
      Computer searches of the Kaiser Permanente Northwest (Portland, Oregon) database
      were performed on the 2-year interval May 2002 to May 2004 to identify new
      diagnoses of chronic prostatitis (International Classification of Diseases, 9th
      Revision code 601.1) and prostatitis not otherwise specified (International
      Classification of Diseases, 9th Revision code 601.9). Of the 1,223 men identified
      with these coded diagnoses, chart reviews were performed on a random subset of
      413 (33.8%). Patients were categorized based on NIH prostatitis definitions of
      type I/II-evidence of pyuria and/or bacteriuria on urinalysis or culture, type
      III-presence of at least 1 of the pain or urinary symptoms in the NIH Chronic
      Prostatitis Symptom Index (pain in the perineum, testicles, tip of penis, pubic
      or bladder area, dysuria, ejaculatory pain, incomplete emptying, urinary
      frequency), type IV-inflammation on prostate biopsy and Other-symptoms other than
      those listed. RESULTS: Of the 413 patients 57 were previously diagnosed with
      prostatitis (prevalent cases), 46 had no evidence of a prostatitis diagnosis in
      the medical record and 7 were treated by physicians outside of the Kaiser
      Permanente Northwest plan. Of the remaining 303 the distribution was 58 type
      I/II, 189 type III, 33 type IV and 23 Other. The incidence of physician diagnosed
      type III prostatitis was 3.3 per 1,000 person-years. If those with isolated
      urinary symptoms were excluded from analysis, the incidence decreased to 2.8 per
      1,000 person-years. The mean age of those with type III prostatitis was 52.9
      years (range 29 to 82). The most common presenting symptoms were dysuria, urinary
      frequency and perineal pain. Symptom duration at presentation was less than 3
      months in 44%, 3 months or greater in 31% and unspecified in 25%. The majority
      (78%) of new prostatitis diagnoses was made by primary care physicians.
      CONCLUSIONS: These data indicate that prostatitis is commonly diagnosed in the
      community setting, and that type III prostatitis accounts for the majority of
      these diagnoses. The duration and complexity of symptoms are less than those
      reported in established prostatitis research cohorts. Most prostatitis diagnoses
      in the community are made by nonurologists.

PMID- 16280833
TI  - Local cost structures and the economics of robot assisted radical prostatectomy.
AB  - PURPOSE: Robot assisted prostatectomy (RAP) is more costly than traditional
      radical retropubic prostatectomy (RRP) under the cost structures at certain
      hospitals. However, this finding may not be the case in all care settings. We
      investigated the sensitivity of RAP and RRP inpatient costs to variations in
      length of stay (LOS), local hospitalization costs and robotic case volume in the
      specialist and generalist settings. MATERIALS AND METHODS: We developed a model
      of RAP vs RRP costs in the specialist and generalist settings using published
      data on operative time and LOS, and cost data from our academic medical center.
      All inpatient cost centers were included, namely surgery costs, professional
      fees, postoperative care, robotic equipment and service. Extensive 1 and 2-way
      sensitivity analyses were performed. RESULTS: Our base case model demonstrated a
      cost premium for RAP vs RRP of USD $783 and $195 in the specialist and generalist
      settings, respectively. Sensitivity analysis of our model assumptions
      demonstrated that RAP could achieve cost equivalence with RRP at a surgical
      volume of 10 cases weekly. If case volume increased to 14 cases weekly, RAP would
      be less expensive than RRP in some practice settings in which RAP LOS was less
      than 1.5 days. CONCLUSIONS: The inpatient costs of robotic assisted prostatectomy
      are volume dependent and cost equivalence with generalist radical retropubic
      prostatectomy is possible at higher volume RAP specialty centers. While RAP may
      be cost competitive with RRP at high cost hospitals or high volume RAP specialist
      centers, this procedure would exist at a cost premium to RRP in other practice
      settings.

PMID- 16280834
TI  - Highlights from the Society of Urologic Oncology, 5th Annual Meeting, December 3
      4, 2004, Bethesda, Maryland, United States of America.
AB  - PURPOSE: The fifth annual meeting of the Society of Urologic Oncology was held
      December 3 and 4, 2004 in Bethesda, Maryland. The program provides a forum for
      the discussion of important issues in genitourinary malignancies among
      urologists, radiation oncologists and medical oncologists. MATERIALS AND METHODS:
      Agenda topics included kidney cancer, bladder cancer and prostate cancer. Several
      sessions featured new developments in basic, translational and clinical research.
      Each session was reviewed for content following the meeting and the highlights
      were summarized. The Young Urologic Oncologists' Forum was again a successful
      component of the meeting but it is beyond the scope of this summary. RESULTS:
      Sessions on kidney cancer focused on molecular genetics and advances in molecular
      therapeutics. Radio frequency ablation of renal masses was also addressed. Topics
      discussed in bladder cancer included screening and surgical management. Dr.
      Donald Skinner received the Huggins Medal and he addressed the society on the
      management of invasive bladder cancer. Reviewed session topics in prostate cancer
      included neoadjuvant treatment paradigms, radiation treatment and adjuvant
      therapy in patients in whom primary treatment has failed. A state-of-the-art
      lecture addressed hereditary prostate cancer. CONCLUSIONS: The Society of
      Urologic Oncology meeting is unique in its multidisciplinary forum and focus on
      urological oncology. The meeting this year highlighted emerging trends, and the
      current state-of-the-art in kidney, bladder and prostate cancer. Additional focus
      was given to new molecular based diagnostic and therapeutic strategies for
      genitourinary malignancies.

PMID- 16280838
TI  - The impact of tumor stage on prognosis in children with adrenocortical carcinoma.
AB  - PURPOSE: We evaluated treatment outcomes in children with adrenocortical
      carcinoma. MATERIALS AND METHODS: We studied 34 children with a median age of 3
      years. In 27 of 28 patients without intracaval extension complete surgical
      excision was accomplished, while tumor resection combined with thrombectomy was
      carried out in 5 of 6 children with vascular invasion. In 2 children with
      cavoatrial thrombus the thrombectomy required cardiopulmonary bypass with deep
      hypothermia and circulatory arrest. Children with incomplete excision of the
      tumor and/or stage IV disease received adjuvant chemotherapy. RESULTS:
      Ultrasonography, computerized tomography and magnetic resonance imaging exhibited
      specificity of 100% in the diagnosis of vascular invasion, and sensitivity of
      50%, 66% and 100%, respectively. Patient age, tumor stage or size and vascular
      invasion were associated with survival in univariate analysis. Tumor stage was
      the only independent factor associated with survival in multivariate analysis.
      The overall 5-year survival rates according to tumor stage were 100% in stage I,
      85% in stage II, 40% in stage III and 0% in stage IV. Of 11 children with local
      recurrence only 2 were alive without disease at 96 and 204 months after
      reoperation with complete tumor excision. Only 2 of 6 patients with vascular
      invasion were disease-free at 17 and 50 months. A total of 10 children with stage
      IV disease treated with chemotherapy died within a median of 6 months.
      CONCLUSIONS: Tumor stage was the most relevant prognostic factor for children
      with adrenocortical carcinoma. Reoperation for local tumor recurrence and
      thrombectomy for inferior vena caval tumor invasion should be attempted whenever
      possible.

PMID- 16280839
TI  - Does the less aggressive multimodal approach of treating bladder-prostate
      rhabdomyosarcoma preserve bladder function?
AB  - PURPOSE: The treatment of bladder-prostate rhabdomyosarcoma has evolved into
      multimodal therapy, including chemotherapy, radiotherapy and organ sparing
      surgery with bladder preservation. We investigated bladder function in children
      who underwent multimodal therapy at our institution and retained the original
      bladder for at least 6 months after treatment ended. MATERIALS AND METHODS: We
      evaluated 8 children with bladder-prostate rhabdomyosarcoma treated at our
      institution between 1999 and 2003 according to inclusion criteria. All patients
      underwent history, physical examination and urodynamic study at least 6 months
      after completion of treatment (range 6 to 39 months). RESULTS: All patients were
      treated following the same chemotherapy and radiotherapy scheme. Three patients
      (37.5%) were asymptomatic and had normal urodynamic studies, and 1 had only
      dysuria (this patient later underwent continent urinary diversion with transverse
      colon). The 4 remaining patients had urological complaints, and the urodynamic
      findings were reduced bladder capacity in 4, overactivity plus sensory urgency in
      2, sensory urgency only in 1 and suprapubic pain during filling in 1.
      CONCLUSIONS: Among 8 patients 3 had normal urinary function and 4 had minor
      tolerable alterations. Cystectomy and urinary diversion were later necessary in
      only 1 patient due to disabling dysuria. The fact that the original functioning
      bladder was preserved in 7 of 8 patients suggests the feasibility of multimodal
      therapy. Long-term followup will still be necessary for definite conclusions,
      since we recognize that the deleterious effects, mainly of radiotherapy, may take
      longer to become evident.

PMID- 16280840
TI  - Clinical manifestations and functional outcomes in children with eosinophilic
      cystitis.
AB  - PURPOSE: Eosinophilic cystitis is a rare disorder, with fewer than 30 pediatric
      cases reported in the literature. We describe our experience with pediatric
      eosinophilic cystitis during a 20-year period. MATERIALS AND METHODS: Four
      children referred to our institution were subsequently diagnosed with
      eosinophilic cystitis between 1984 and 2004. A retrospective chart review was
      performed to assess clinical presentation, diagnosis, treatment and outcomes.
      RESULTS: Mean patient age at presentation was 10.8 years (range 5 to 18) and male
      to-female ratio was 3:1. All 4 patients presented with irritative urinary
      symptoms, including 3 with dysuria and/or gross hematuria and 2 with urinary
      frequency, lower abdominal pain and/or a concomitant urinary tract infection.
      Allergic diseases (asthma, allergic rhinitis, etc) were present in 3 patients,
      and a formal allergen skin test was positive in 2 of those tested. A bladder mass
      mimicking malignancy was documented in 2 patients. Three patients had symptom
      resolution with conservative treatment, while 1 had development of an unremitting
      tumefactive process that eventually required partial cystectomy and bladder
      augmentation. CONCLUSIONS: Eosinophilic cystitis is a rare condition with a wide
      range of clinical manifestations. Children can present with a bladder mass
      mimicking sarcoma, underscoring the need for biopsy before diagnosis and
      treatment of a presumed oncological process. The condition usually follows a
      benign course, although unremitting progression remains a possibility.

PMID- 16280841
TI  - New concepts in feminizing genitoplasty--is the Fortunoff flap obsolete?
AB  - PURPOSE: We retrospectively evaluated the results of an original technique that
      combines mobilization of the urogenital sinus with the creation of urogenital
      flaps to enlarge the vaginal introitus for 1-stage feminizing genitoplasty in
      children with urogenital sinus anomalies, thus, avoiding the use of posteriorly
      based perineal flaps. MATERIALS AND METHODS: A total of 11 patients with
      urogenital sinus anomalies have undergone a modified Fortunoff technique
      combining total urogenital mobilization with the creation of urogenital sinus
      flaps by a single surgeon (RG) since 1998. Patient age at surgery ranged from 3
      months to 13 years (mean 3.8 years). Diagnoses included congenital adrenal
      hyperplasia in 7 patients, cloacal malformation in 2 and urogenital sinus
      malformation in 2. Eight patients underwent a perineal approach and 3 underwent a
      posterior sagittal approach. RESULTS: Followup ranged from 3 months to 5 years
      (mean 2.5 years). The cosmetic appearance was considered superior to that
      achieved with previous techniques. The vagina had a more physiological position
      in all patients except 1, and no patient had development of vaginal stenosis. One
      patient had development of a mild mid urethral stricture that required a single
      dilation using anesthesia. In this patient cystourethroscopy performed 3 years
      later was normal. CONCLUSIONS: We believe that the redundant urogenital sinus
      tissue must not be discarded, but rather incorporated into the reconstruction of
      the posterior vaginal wall, thus, avoiding the use of perineal skin flaps. This
      modification allows placement of the vaginal opening in a more physiological
      position with a better cosmetic appearance than previous techniques.

PMID- 16280842
TI  - A multicenter evaluation of technical preferences for primary hypospadias repair.
AB  - PURPOSE: Considerable controversy exists regarding the optimal surgical technique
      for the repair of mid shaft and proximal hypospadias. We sought to evaluate
      differences in surgical preferences among an international cohort of pediatric
      urologists. MATERIALS AND METHODS: An anonymous questionnaire containing relevant
      demographic data as well as choices of technique to repair 5 representative
      hypospadias cases was developed and administered. RESULTS: Of 121 pediatric
      urologists contacted 101 completed the survey, representing an 83% response rate.
      The majority were full-time academic pediatric urologists who performed 6 to 10
      hypospadias surgeries monthly. A total of 92 respondents (confidence interval
      [CI) 0.84 to 0.96) preferred the tubularized incised urethral plate (TIP)
      technique for the repair of distal hypospadias. Similarly, 82 (CI 0.72 to 0.88)
      preferred TIP for the repair of mid shaft hypospadias. The 2 most common
      techniques for repair of proximal hypospadias without chordee, preferred by 43
      correspondents each (CI 0.33 to 0.53), were TIP and transverse island flap (TVIF)
      onlay. For repair of moderate (30-degree to 40-degree) chordee dorsal plication
      was preferred by 82 respondents, while a ventral approach was preferred by 12.
      When moderate chordee was associated TVIF onlay was preferred by 35 (CI 0.26 to
      0.45) and TIP by 24 respondents (CI 0.16 to 0.34). For severe chordee (greater
      than 50 degrees) 31 respondents preferred dorsal plication, while 68 chose some
      form of ventral repair. Among the respondents 37 approach proximal hypospadias
      associated with severe chordee using a staged procedure, while 40 use a single
      stage procedure using a TVIF tube (CI 0.30 to 0.50). Using Spearman's rank
      correlation coefficient, no significant correlations were identified between
      respondent practice demographics and choice of repair for each hypothetical
      hypospadias case. CONCLUSIONS: In this cohort of pediatric urologists we observed
      that the majority prefers TIP to repair distal and mid shaft hypospadiac defects.
      Significant variability exists for preferred technique for proximal hypospadias
      and chordee correction. These results support the need for prospective trials
      comparing techniques for the repair of proximal hypospadias.

PMID- 16280843
TI  - A multivariable assessment of renal size and growth of scarred kidneys in
      children.
AB  - PURPOSE: We applied a recently developed multivariable renal size nomogram to
      sonographic measurements of kidneys with known scarring to assess systematically
      their sizes and growth patterns compared to normal kidneys. MATERIALS AND
      METHODS: We retrospectively reviewed renal sonograms of 138 kidneys (55 right and
      83 left) with known scarring. The sizes of these scarred kidneys were compared to
      the 95% prediction limits calculated according to the multivariable renal size
      nomogram, adjusting for patient age, gender, race, weight and height. The growth
      of scarred kidneys was evaluated by fitting individual linear regression lines
      using serial sonographic measurements and comparing the results with normal
      predicted values. RESULTS: The sizes of 89.1% of the right and 81.9% of the left
      scarred kidneys were within the 95% normal prediction limits. Only 17 of 138 of
      the scarred renal units showed smaller kidney sizes compared to the normal
      prediction limits. Serial sonographic measurements revealed that compared to
      normal predicted values, 24 of 60 left and 16 of 38 right scarred kidneys grew
      within +/- 1.0% annually of the boundaries of normal predicted values.
      Additionally, 8 left and 7 right scarred kidneys indicated a growth rate of more
      than 1% annually higher than the normal predicted values. CONCLUSIONS:
      Multivariable analyses of renal sonographic measurements provided a dynamic
      picture of kidney well-being in children with renal scarring. We found that the
      majority of scarred kidneys were within the normal predicted limits, and a large
      proportion of these kidneys grew equally well compared to those with normal
      anatomy.

PMID- 16280844
TI  - Management of the failed pyeloplasty: a contemporary review.
AB  - PURPOSE: We reviewed our experience with open dismembered pyeloplasty, with
      specific focus on the presentation and management of failed pyeloplasty in the
      pediatric population. MATERIALS AND METHODS: We performed a retrospective review
      of patients who had undergone open dismembered pyeloplasty between 1998 and 2003.
      All patients with less than 6 months of followup were excluded from analysis. The
      patients were followed postoperatively with serial ultrasounds, with renograms
      reserved for those patients with prolonged, persistent or worsening
      hydronephrosis, or recurrent symptoms during followup. RESULTS: A total of 105
      pyeloplasties were performed in 103 patients (71 males and 32 females) 1 to 204
      months old (mean 60), with an overall success rate of 93.3%. Followup ranged from
      6 to 69 months (mean 23). The 7 patients with treatment failure were males 1 to
      204 months old (mean 125), who presented most commonly with pain within 3 to 38
      months (mean 13.1) after initial surgery. Subsequent ultrasound revealed
      worsening hydronephrosis, and renography in these patients showed a pattern
      consistent with obstruction. Five patients underwent initial balloon dilation, in
      which 1 was successful. In addition, 1 of these patients underwent an
      unsuccessful antegrade laser endopyelotomy. Six patients (86%) underwent open
      surgery, consisting of ureterocalicostomy in 3 and reoperative dismembered
      pyeloplasty in 3. Dense scarring was seen in all patients, 2 patients had a
      redundant pelvis causing kinking and 2 patients had unrecognized crossing
      vessels. Overall salvage rate was 100% with continued followup of 3 to 50 months
      (mean 18). CONCLUSIONS: Dismembered pyeloplasty was successful in the vast
      majority of patients. In our series failures occurred as late as 3 years
      postoperatively, although most presented within 12 months of followup. Excluding
      routine postoperative nuclear renography did not seem to affect our ability to
      identify these cases. Although anatomical features such as renal pelvic size may
      have a role, failure is most likely secondary to technical issues, including
      missed crossing vessels and dependency of the anastomosis. In this series failed
      pyeloplasties did not respond well to balloon dilation, likely due to scar
      formation. Our current practice is to manage failures by open surgery, although
      endoscopic management by an incision may be an option.

PMID- 16280845
TI  - Testicular hypotrophy does not correlate with grade of adolescent varicocele.
AB  - PURPOSE: Testicular hypotrophy is the most widely accepted indication for
      correcting adolescent varicocele. Previous studies in adolescents have shown a
      relationship between increasing grade of varicocele and the likelihood of
      testicular hypotrophy. As this relationship has significant clinical
      implications, we studied the correlation between grade and testicular volume
      disproportion in our adolescent varicocele population. MATERIALS AND METHODS: We
      reviewed the adolescent varicocele database at our institution. A total of 168
      patients 8 to 21 years old were studied. We routinely calculated testis volumes
      using scrotal ultrasound. Testicular disproportion was calculated using the
      equation [(size of unaffected testis) - (size of affected testis)]/(size of
      unaffected testis) x 100%. Disproportion was categorized as less than 10%, 10% to
      20% and more than 20%. Varicoceles were graded by an attending urologist with the
      patient standing, using the system of Dubin and Amelar. Analysis of variance and
      Pearson chi-square indicated no significant differences in volume differential
      between varicocele grades. RESULTS: Mean +/- SD volume differential was 18% +/-
      15% for grade I, 25% +/- 20% for grade II and 19% +/- 14% for grade III. ANOVA
      revealed no significant difference in mean volume differential between the 3
      varicocele grades (p = 0.10). When categorizing patients into 3 levels of volume
      differential (less than 10%, 10% to 20%, more than 20%) no significant
      correlation was observed between varicocele and volume differential (p = 0.48,
      chi-square test). CONCLUSIONS: Grade of varicocele does not correlate with
      presence or severity of testicular disproportion in adolescent boys with
      varicocele as measured by scrotal ultrasound.

PMID- 16280849
TI  - Phyllodes tumor of the prostate.

PMID- 16280850
TI  - Left inferior vena cava in a living kidney donor.

PMID- 16280851
TI  - Fluorescence guided optical coherence tomography for the diagnosis of early
      bladder cancer in a rat model.
AB  - PURPOSE: We describe the technique of fluorescence image guided optical coherence
      tomography (FG-OCT). We examined its ability to enhance specificity and
      sensitivity for the noninvasive diagnosis of early bladder cancer. MATERIALS AND
      METHODS: Transitional cell carcinoma was developed in 54 Fisher 344 female rats
      by intravesical methyl-nitroso-urea instillations. Two or three rats were
      diagnosed sequentially by 5-ALA (5-aminolevulinic acid hydrochloride) induced
      fluorescence imaging, cross-sectional OCT and histological microscopy weekly
      during weeks 11 to 33 following initial methyl-nitroso-urea instillation to track
      the course of carcinogenesis. RESULTS: The specificity of fluorescence detection
      was significantly enhanced by FG-OCT (53% and 93%, respectively, p <0.0001). The
      sensitivity of fluorescence detection and FG-OCT was 79% and 100%, respectively.
      CONCLUSIONS: FG-OCT cystoscopy has the potential to diagnose early bladder cancer
      with high sensitivity and specificity with drastically decreased imaging time
      compared to that of white light guided OCT cystoscopy.

PMID- 16280852
TI  - Regulation of tight junction proteins and bladder epithelial paracellular
      permeability by an antiproliferative factor from patients with interstitial
      cystitis.
AB  - PURPOSE: Previous reports have suggested that the bladder epithelial barrier may
      be compromised in interstitial cystitis (IC). Antiproliferative factor (APF) is a
      small glycoprotein made specifically by bladder epithelial cells in patients with
      IC that induces changes in expression of certain epithelial cell proteins and
      profoundly inhibits cell growth. Therefore, we confirmed the increased
      permeability and decreased tight junction formation of bladder epithelial cell
      monolayers grown from biopsies in patients with IC compared to cells from normal
      controls. We then determined the effect of APF on the permeability of normal
      bladder epithelial cell monolayers and the expression of tight junction proteins.
      MATERIALS AND METHODS: Permeability was determined by measuring the C-mannitol
      and H-inulin flux between cells in confluent monolayers on Transwell culture
      plates (Corning, Corning, New York). Tight junction formation was assessed by
      immunofluorescence microscopy and the expression of specific proteins was
      determined by Western blot. RESULTS: APF treatment caused significant increases
      in the paracellular permeability of normal bladder epithelial cell monolayers and
      the attenuation of tight junctions compared to mock APF, similar to changes seen
      in IC cells. APF treatment also decreased expression of the tight junction
      proteins zonula occludens-1 and occludin. CONCLUSIONS: Because of its apparent
      effects on bladder epithelial cell tight junctions and paracellular permeability
      in vitro, APF may contribute to the leakiness of the bladder epithelial barrier
      seen in IC.

PMID- 16280853
TI  - Dual pulse shock wave lithotripsy: in vitro and in vivo study.
AB  - PURPOSE: We evaluated the performance of a novel dual pulse lithotriptor for
      extracorporeal lithotripsy. MATERIALS AND METHODS: A piezoelectric lithotriptor
      was modified to produce pairs of successive (tandem) shock waves. Four kidney
      stone models were exposed in vitro to 500 single shock waves with a standard
      lithotriptor. Another set of stones was exposed 1 at a time to 250 pairs of shock
      waves with the tandem lithotriptor. The time delay between the first and second
      shock waves was increased in steps of 50 microseconds between 100 and 600
      microseconds. Four stones were used per delay, ie 44 phantoms were fractured with
      the tandem system. Rabbits were used in vivo to demonstrate that the novel device
      does not produce more tissue trauma. Five rabbits were exposed to shock waves
      generated by the new device, 5 were treated with the standard system and 5 served
      as the sham treated group. Renal damage caused by the 2 systems was compared 1
      week after shock wave application. RESULTS: Enhanced fragmentation efficiency was
      achieved at a delay of 250 microseconds. In vivo results indicate that the dual
      pulse shock wave generator does not produce more kidney tissue damage.
      CONCLUSIONS: Tandem lithotriptors may improve the quality and rate of stone
      comminution without increasing tissue damage. The device enhances cavitation
      induced damage to kidney stones. Extensive in vivo experiments will be important
      to evaluate the new design.

PMID- 16280854
TI  - The effects of botulinum-A toxin on bladder function and histology in spinal cord
      injured rats: is there any difference between early and late application?
AB  - PURPOSE: We explored the effects of early and late application of botulinum-A
      toxin (BTX-A) on reservoir function and histological bladder changes in spinal
      cord injured rats. MATERIALS AND METHODS: The study was done in 30 Sprague-Dawley
      rats randomly allocated into 5 groups. Group 1 of 6 rats underwent sham operation
      only. Group 2 of 6 rats underwent spinal cord transection. Group 3 of 6 rats
      underwent spinal cord transection followed by BTX-A application into the detrusor
      muscle 7 days later. Group 4 of 6 rats underwent spinal cord transection,
      followed by BTX-A application into the detrusor muscle 28 days later. Group 5 of
      6 rats underwent spinal cord transection followed by saline injection into the
      detrusor muscle after 28 days. Spinal cord injury was created by transecting the
      cord at the T9 to T10 level. All rats underwent cystometric examination initially
      and on day 42 before sacrifice. The bladders were removed and examined
      histologically for fibrosis and hyperplasia. RESULTS: On cystometric examination
      BTX-A caused an improvement in baseline pressure, and the frequency and amplitude
      of uninhibited detrusor contractions (p <0.001). No significant differences were
      observed in maximal bladder capacity or urethral opening pressure (p >0.05).
      Histologically BTX-A led to decreased fibrosis and hyperplasia (p <0.001). No
      significant differences were found between histological or cystometric among the
      groups with respect to receiving BTX-A in the early and late periods (p >0.05).
      CONCLUSIONS: BTX-A has a functional and histological healing effect on detrusor
      hyperreflexia subsequent to spinal cord injury in rats. Although administering
      BTX-A in the early period had better quantifiable functional and histological
      outcomes compared to the late period, the difference was not statistically
      significant.

PMID- 16280855
TI  - Intrathecal or dietary glycine inhibits bladder and urethral activity in rats
      with spinal cord injury.
AB  - PURPOSE: We examined the influence of intrathecal or dietary glycine on bladder
      and urethral activity in rats with spinal cord injury. MATERIALS AND METHODS: A
      total of 20 female Sprague-Dawley rats were used 4 weeks after lower thoracic
      spinal cord injury. The rats were divided into standard and 1% glycine diet
      groups. In the standard diet group isovolumetric cystometry and urethral pressure
      measurement were performed before and after intrathecal injection of glycine. In
      the 1% glycine diet group bladder and urethral activity were compared with
      control recordings in the standard diet group. RESULTS: In the standard diet
      group intrathecal injection of glycine prolonged the interval and decreased the
      amplitude of bladder contractions, decreased baseline urethral pressure and
      altered urethral activity during bladder contraction from a pattern of detrusor
      sphincter dyssynergia to detrusor-sphincter synergy at 100 mug glycine. In the 1%
      glycine diet group the interval and amplitude of bladder contractions were
      prolonged and decreased, respectively, compared with those in the standard diet
      group. Baseline urethral pressure was lower than in the standard diet group even
      after intrathecal injection of 100 mug glycine. Urethral pressure did not change
      during bladder contraction and it was the same as baseline pressure. Residual
      urine volume was lower than in the standard diet group. CONCLUSIONS: Intrathecal
      or dietary glycine inhibits bladder and urethral activity, and improves detrusor
      hyperreflexia and detrusor-sphincter dyssynergia.

PMID- 16280856
TI  - Biocompatibility and implantation properties of 2 differently braided,
      biodegradable, self-reinforced polylactic acid urethral stents: an experimental
      study in the rabbit.
AB  - PURPOSE: Biodegradable urethral stents have been in clinical use for more than 10
      years. To solve the problems connected with the helical spiral configuration of
      the stents used to date we developed a new tubular mesh configuration and
      evaluated the biocompatibility properties and degradation time of 2 differently
      braided stents in the rabbit urethra. MATERIALS AND METHODS: The biodegradable,
      self-expanding stents were made of self-reinforced polylactic acid polymer
      blended with BaSO4 (Alfa Chem, Kings Point, New York). Two braiding patterns,
      namely a diamond 1/1 and a regular 2/2 + 1 (Prodesco, Perkasie, Pennsylvania),
      were used to produce a tubular mesh configuration. Stainless steel stents with
      1/1 braiding served as controls. The stents were inserted into the posterior
      urethra of 36 male rabbits. The animals were sacrificed after 1 week, 1 month, 6
      months or 12 months. Light microscopy and scanning electron microscopy analyses
      were done. RESULTS: Tissue reactions to operative trauma were seen in all
      specimens at week 1. The changes gradually abated in the biodegradable stent
      groups, whereas chronic inflammatory changes and fibrosis were increasingly seen
      with metallic stents after 6 months. Epithelial hyperplasia increased with time
      for all stent types and materials. As expected, stent fragmentation started at 6
      months. CONCLUSIONS: Biodegradable polymers are suitable materials for braided
      urethral stents. However, the braided configuration of the stent with a decreased
      mass of material does not prevent the development of epithelial hyperplasia. The
      biodegradable, self-expanding, braided stents functioned well in the rabbit
      urethra and are suitable for clinical studies.

PMID- 16280857
TI  - Possible mechanism of referred pain in the perineum and pelvis associated with
      the prostate in rats.
AB  - PURPOSE: Since persistent pain in the perineum and pelvic floor associated with
      chronic prostatitis /chronic pelvic pain syndrome has been hypothesized to be
      referred pain, it might also be explained by neural mechanisms. MATERIALS AND
      METHODS: Dual retrograde fluorescent labeling and immunohistochemistry were
      identified as methods with which to investigate the neurogenic aspect of this
      status. The dual distribution of dorsal root ganglia (DRG) cells was determined
      after double retrograde fluorescent staining of the prostate and pelvic floor,
      and the prostate and perineum somatic nerves. Calcitonin gene-related peptide
      (CGRP) and substance P (SP) in dual labeled cells were determined by
      immunohistochemistry, giving possible insight into the cause of pelvic pain.
      RESULTS: Fluorescent double labeled cells were found in the lumbar and sacral
      DRG, while double labeled cells were distributed predominantly in L6 to S1 and L1
      to L2 segment DRG in groups 1 and 2, respectively. On immunohistochemistry some
      of them were confirmed to contain CGRP and SP. Thus, there are crossover pathways
      between the prostate and pelvic floor. CONCLUSIONS: The findings that we present
      confirm that the peripheral process of DRG cells dichotomizes to the prostate,
      sphincter and somatic parties simultaneously. Some of these cells contain CGRP
      and SP, which indicate that referred pain in the perineum and pelvic floor may be
      caused by an axon reflex in the peripheral process of DRG neurons.

PMID- 16280858
TI  - Prostanoid transport by multidrug resistance protein 4 (MRP4/ABCC4) localized in
      tissues of the human urogenital tract.
AB  - PURPOSE: The seminal vesicles are the major source of prostaglandins in seminal
      fluid. For prostanoid action on cell surfaces they must be released from
      synthesizing cells. MRP4/ABCC4 (multidrug resistance protein 4 adenosine
      triphosphate-binding cassette, subfamily C, member 4) is an adenosine
      triphosphate dependent export pump for organic anions that may mediate prostanoid
      transport across the plasma membranes. Therefore, we analyzed whether MRP4 is
      expressed in the seminal vesicles and other tissues of the human urogenital
      tract, whether MRP4 and prostanoid synthesizing enzymes are co-expressed in the
      same cell type and whether MRP4 functions as a prostanoid export pump. MATERIALS
      AND METHODS: The expression and localization of MRP4 and prostanoid synthesizing
      enzymes were investigated in several tissues of the male human urogenital tract
      by immunoblot and immunofluorescence analyses. Prostanoid transport was measured
      into inside-out membrane vesicles from cells expressing recombinant human MRP4.
      RESULTS: MRP4 and prostanoid synthesizing enzymes were co-expressed in the
      epithelial cells of human seminal vesicles. Moreover, MRP4 was localized in the
      plasma membrane of epithelial cells of the ureter, in the basolateral membrane of
      glandular epithelial cells of the prostate, and in smooth muscle cells of the
      bladder and corpus cavernosum. Transport studies established MRP4 as an efflux
      pump for prostaglandin E2 (Michaelis constant [Km] 3.5 muM), thromboxane B2 (Km
      9.9 muM) and prostaglandin F2alpha (Km 12.6 muM). CONCLUSIONS: The co-expression
      of prostanoid synthesizing enzymes and MRP4 in epithelial cells of the human
      seminal vesicles and the function of MRP4 as a prostanoid efflux pump indicate
      that MRP4 mediates prostanoid transport from these cells, which are the main
      prostanoid synthesizing cells in the male urogenital tract.

PMID- 16280859
TI  - Effect of epidermal growth factor on spermatogenesis in the cryptorchid rat.
AB  - PURPOSE: Epidermal growth factor (EGF) is secreted mainly from the submandibular
      glands. Submandibular gland ablation causes a marked decrease in male fertility,
      which suggests that EGF influences spermatogenesis. We investigated the effect of
      EGF in combination with orchiopexy on cryptorchid rat testes in which tubular
      deterioration had become partially irreversible. MATERIALS AND METHODS:
      Unilaterally cryptorchid rats were obtained by daily administration of 7.5 mg
      flutamide (Nihonkayaku, Tokyo, Japan), an androgen receptor antagonist, to
      pregnant rats. At age 10 weeks the unilaterally cryptorchid rats underwent
      orchiopexy with or without EGF administered into the cryptorchid testis. EGF
      solution (10 microg/ml) was delivered into the seminiferous tubules by retrograde
      perfusion through the rete testis. At 14 days testicular recovery was assessed
      based on the maturity of spermatogenesis using a modified Johnsen score and from
      the number of apoptotic germ cells per seminiferous tubule. RESULTS: Mean Johnsen
      score +/- SEM was significantly higher in the orchiopexy with EGF than in the
      orchiopexy without EGF group (7.85 +/- 0.12 vs 7.12 +/- 0.13, p <0.001). The
      number of apoptotic germ cells tended to be smaller in the orchiopexy with EGF
      group than in the orchiopexy without EGF group (0.16 +/- 0.05 vs 0.28 +/- 0.08).
      CONCLUSIONS: Although orchiopexy for cryptorchidism partly improved
      spermatogenesis, recovery was limited. EGF administered in combination with
      orchiopexy was more effective for spermatogenesis than orchiopexy alone. This may
      be applicable in patients with cryptorchidism.

PMID- 16280863
TI  - Re: C-reactive protein: a biomarker of survival in patients with metastatic renal
      cell carcinoma treated with subcutaneous interleukin-2 based immunotherapy.

PMID- 16280864
TI  - Re: The accuracy of 250 fine needle biopsies of renal tumors.

PMID- 16280865
TI  - Re: The accuracy of 250 fine needle biopsies of renal tumors.

PMID- 16280866
TI  - Re: A prospective analysis of the time to normalization of serum androgens
      following 6 months of androgen deprivation therapy in patients on a randomized
      phase III clinical trial using limited hormonal therapy.

PMID- 16280868
TI  - Re: prevalence of testicular intraepithelial neoplasia in healthy males.

PMID- 16280869
TI  - Re: Lymphatic sparing laparoscopic varicocelectomy: a microsurgical repair.

PMID- 16280870
TI  - Re: Percutaneous management of calculi within horseshoe kidneys.

PMID- 16280872
TI  - Re: Transobturator vaginal tape inside out for the surgical treatment of female
      stress urinary incontinence: anatomical considerations.

PMID- 16280875
TI  - Re: Is benign prostatic hyperplasia a risk factor for chronic renal failure?

PMID- 16280889
TI  - Managing phantom limb pain.

PMID- 16280890
TI  - How to assess phenytoin levels.

PMID- 16280891
TI  - Getting down to the lower GI tract.

PMID- 16280894
TI  - HIPAA guidelines for using PDAs.

PMID- 16280895
TI  - Improving care for patients with subarachnoid hemorrhage.

PMID- 16280896
TI  - Giving medication by retrograde infusion.

PMID- 16280901
TI  - Too many problems.

PMID- 16280921
TI  - Preventing perioperative complications in special populations.

PMID- 16280923
TI  - What do men in nursing really think? Survey respondents speak out.

PMID- 16280924
TI  - Stroke (brain attack).

PMID- 16280925
TI  - Take charge with an automated external defibrillator.

PMID- 16280927
TI  - Systemic lupus erythematosus: unmasking a great imitator.

PMID- 16280926
TI  - Diamond in the rough.

PMID- 16280929
TI  - Keeping respiratory syncytial virus at bay.

PMID- 16280936
TI  - Testing the corneal reflex.

PMID- 16280937
TI  - Assessing venous ulcers and venous insufficiency.

PMID- 16280938
TI  - What is atlantoaxial instability?

PMID- 16280939
TI  - Vibrio vulnificus.

PMID- 16280941
TI  - Mitral valve regurgitation after myocardial infarction.

PMID- 16280942
TI  - Pediatric intravenous insertion in the emergency department: bevel up or bevel
      down?
AB  - OBJECTIVE: Intravenous catheters are usually inserted with the bevel facing up.
      Bevel down may be superior in small and/or dehydrated children. We seek to
      determine whether there is a difference in the success rate of intravenous
      insertion using these 2 methods. METHODS: We recruited children requiring an
      intravenous catheter in the emergency department where there was time to obtain
      consent. Patients were randomized to have the first attempt bevel up or bevel
      down. If the first attempt was unsuccessful, the alternate technique was used on
      second attempt. Attempts beyond 2 were not tracked. RESULTS: We recruited 428
      patients. Data are available from 396 (201 bevel-up and 195 bevel-down
      techniques). At least 63 different nurses participated. The nurses participated
      in the study a median number of 2 times (maximum, 36). Four nurses used the bevel
      down technique more than 10 times. The success rate on first attempt was 75.6%
      (95% confidence interval [CI], 69.8-81.4) for bevel up and 60% (95% CI, 53.2
      66.8) for bevel down. The success rate on second attempt was 56.8% (95% CI, 45.3
      68.2) for bevel up and 42.9% (95% CI, 30.3-55.5) for bevel down. In the subgroup
      of infants weighing less than 5 kg, there was no difference between the 2
      techniques on the first attempt, with bevel up having a success of 33% (95% CI,
      8.4-57.6) and bevel down 30% (95% CI, 4.1-55.9). CONCLUSIONS: The bevel-up
      technique performed superior to bevel-down technique in this study. The bevel
      down technique might be useful in small infants.

PMID- 16280943
TI  - Child life intervention during angiocatheter insertion in the pediatric emergency
      department.
AB  - OBJECTIVE: Current literature is deficient regarding the scope of procedures for
      which certified child life specialist (CCLS) services are effective in the
      pediatric emergency department. The purpose of this study is to analyze the
      effect of CCLS intervention during routine peripheral venous angiocatheter
      insertion on child procedure-related distress. METHODS: Eligible children were
      aged 2 to 16 years. Subjects were randomly assigned to CCLS intervention or
      standard care. The Observation Scale of Behavior Distress-revised (OSBD-r) [J
      Pediatr Psychol 12 (1987) 543] was recorded during the procedure. Secondary
      outcomes included child and parent State Trait Anxiety Inventories [Manual for
      the State-Trait Anxiety Inventory (1973) and Manual for the State-Trait Anxiety
      Inventory for Children (1973)] and an adapted parent customer satisfaction survey
      [Eval Program Plann 5 (1982) 233; Eval Program Plann 6 (1983) 299; and J Paediatr
      Child Health 31 (1995) 435]. Explanatory and intention-to-treat analyses were
      performed. RESULTS: One hundred forty-nine children completed the study. Although
      there was no statistical difference in mean total OSBD-r in the intention-to
      treat analysis, the mean difference of 0.61 OSBD units (95% confidence interval,
      0.04-1.19) in the anticipation phase in the 4- to 7-year age group was
      statistically significant. When the patients with only 1 insertion attempt were
      analyzed (n = 121), the total OSBD-r, anticipation, and preparation phase
      differences were statistically significant in the intention-to-treat analysis. In
      the explanatory analysis (n = 138), a mean significant difference in total OSBD-r
      score of 1.80 (95% confidence interval, 0.19-3.42) was found. There were no
      significant differences in child or parent anxiety or customer satisfaction
      between groups. CONCLUSIONS: CCLS intervention may reduce the behavioral stress
      associated with angiocatheter insertion, especially in children aged 4 to 7
      years. These data further support the role of the CCLS as a patient and family
      advocate during routine procedures.

PMID- 16280944
TI  - Emergency department pediatric all-terrain vehicle injuries in West Central
      Illinois.
AB  - OBJECTIVES: This study was prepared to evaluate pediatric all-terrain vehicle
      related injuries treated in a tertiary care emergency department in West Central
      Illinois. METHODS: A retrospective descriptive study was performed of local
      emergency department cases entered into the US Consumer Product Safety Commission
      database. All visits involving an all-terrain vehicle-related injury in children
      younger than 18 years from January 1994 to December 2001 were explicitly reviewed
      and compared with aggregate national Consumer Product Safety Commission pediatric
      all-terrain vehicle data. RESULTS: One hundred eighty-seven children (age range,
      2-17 years) from 14 West Central Illinois counties were treated in the emergency
      department during the study period. Injury patterns followed a national trend of
      an increasing annual incidence after 1998 (P = 0.05). The majority of patients
      were boys (78%) and were 12 years or younger (71%). Contusions (31.8%), fractures
      (25%), and lacerations (18.8%) accounted for the majority of injuries. Although
      observed injuries correlated well with national injury estimates for injury
      position, age, and sex, more head and chest injuries were noted locally. Derived
      injury severity scores had a mean of 3.1 (range, 1-50), and no difference was
      noted in the injury severity score for helmet use, sex, or age younger than 12
      years. CONCLUSIONS: Overall, the incidence of all-terrain vehicle-related
      injuries in West Central Illinois in the emergency department is increasing, and
      local injury patterns correlate well with those reported on a national level.

PMID- 16280945
TI  - Pediatric emergencies on a US-based commercial airline.
AB  - OBJECTIVES: The purpose of this investigation was to determine the incidence and
      character of pediatric emergencies on a US-based commercial airline and to
      evaluate current in-flight medical kits. METHODS: In-flight consultations to a
      major US airline by a member of our staff are recorded in an institutional
      database. In this observational retrospective review, the database was queried
      for consultations for all passengers up to 18 years old between January 1, 1995,
      and December 31, 2002. Consultations were reviewed for type of emergency, use of
      the medical kit, and unscheduled landings. RESULTS: Two hundred twenty-two
      pediatric consultations were identified, representing 1 pediatric call per 20,775
      flights. The mean age of patients was 6.8 years. Fifty-three emergencies were
      preflight calls, and 169 were in-flight pediatric consultations. The most common
      in-flight consultations concerned infectious disease (45 calls, 27%),
      neurological (25 calls, 15%), and respiratory tract (22 calls, 13%) emergencies.
      The emergency medical kit was used for 60 emergencies. Nineteen consultations
      (11%) resulted in flight diversions (1/240,000 flights), most commonly because of
      in-flight neurological (9) and respiratory tract (5) emergencies. International
      flights had a higher incidence than domestic flights of consultations and
      diversions for pediatric emergencies. CONCLUSIONS: The most common in-flight
      pediatric emergencies involved infectious diseases and neurological and
      respiratory tract problems. Emergency medical kits should be expanded to include
      pediatric medications.

PMID- 16280946
TI  - A randomized controlled trial of sport helmet interventions in a pediatric
      emergency department.
AB  - OBJECTIVE: To evaluate the effectiveness of 3 competing pediatric emergency
      department (ED) interventions aiming to increase sport helmet use in a state
      without helmet legislation. METHODS: A randomized controlled clinical trial was
      conducted during the 7-month period between April and October 2003 at an urban
      pediatric ED in a state without current helmet legislation. We enrolled 200
      assenting English-speaking children aged 5 to 16 years, admitted to the ED for
      treatment, and who did not currently own a helmet. Participants were randomized
      into 3 experimental arms. A control group received usual care, that is, verbal
      counseling regarding helmet use. Subjects in one treatment arm received a voucher
      to receive a free helmet that could be redeemed at a different location within
      the hospital. Subjects in a second treatment arm actually received a free helmet
      directly in the ED. The main outcome measure was reported helmet use at follow
      up, assessed by telephone interviews of both the child and a parent. RESULTS:
      Directly receiving a free helmet in the ED significantly increased reported
      helmet use relative to the control group; the odds that a parent reported helmet
      use were nearly 16 times higher (P < 0.01), and the odds that a child reported
      helmet use were nearly 10 times higher (P < 0.01). Receiving a free helmet also
      significantly increased reported helmet use when compared with the voucher
      intervention group. Reported use between the control group and the voucher
      intervention group was not significantly different. CONCLUSIONS: Directly
      receiving a free helmet in the pediatric ED appears to be an effective hospital
      based strategy to increase pediatric helmet use.

PMID- 16280947
TI  - Preprocedural fasting state and adverse events in children receiving nitrous
      oxide for procedural sedation and analgesia.
AB  - STUDY OBJECTIVE: Established fasting guidelines for analgesia and sedation are
      difficult to follow in the emergency department (ED), and the association between
      preprocedural fasting and adverse events has been questioned. We characterize the
      fasting status of patients receiving procedural sedation and analgesia with
      nitrous oxide (N2O) in a pediatric ED and assess the relationship between fasting
      status and adverse events. METHODS: A prospective case series was conducted in a
      children's hospital ED over an 8-month period. Patients receiving N2O for
      procedural sedation and analgesia were enrolled and followed up by telephone
      call. Preprocedural fasting state and adverse events, as well as N2O
      concentration, adjunctive drugs, and deepest level of sedation, were recorded.
      Adverse events were analyzed in relation to fasting status. RESULTS: Two hundred
      twenty children who underwent procedural sedation and analgesia with N2O were
      enrolled. Fasting status was obtained in 218 patients (99.1%). Of these, 155
      (71.1%; 95% confidence interval [CI], 64.5%-77.0%) did not meet fasting
      guidelines for solids There were no serious adverse events and no episodes of
      aspiration (1-sided 97.5% CI, 0%-1.7%). While in the ED, 46 minor adverse events
      occurred in 37 patients (16.8%; 95% CI, 12.1%-22.4%). Emesis occurred in 15
      patients (7%), including 4 (6.3%; 95% CI, 1.8%-15.5%) of 63 patients who met and
      in 11 (7.1%; 95% CI, 3.6%-12.3%) of 155 patients who did not meet fasting
      guidelines for solids. There was no significant difference in median fasting
      duration between patients with and without emesis. CONCLUSION: Seventy-one
      percent of patients undergoing ED procedural sedation and analgesia with N2O did
      not meet established fasting guidelines. In this series, there was no association
      between preprocedural fasting and emesis. There were no serious adverse events.

PMID- 16280948
TI  - Pediatric body packing: drug smuggling reaches a new low.
AB  - The case of a 6-year-old boy presenting with severe clinical manifestations of an
      opioid intoxication and who is discovered to be an international "body packer" is
      presented and discussed. This article is the first to report on the phenomenon of
      body packing in young children. It also highlights the use of prescription
      opioids as cargo, which has not previously been addressed in the literature.

PMID- 16280949
TI  - Limping child with profound weakness.

PMID- 16280951
TI  - True-true, unrelated: a case report.
AB  - OBJECTIVES: Sudden cardiac deaths in previously healthy children are frequently
      due to undiagnosed cardiovascular diseases, either congenital or acquired. In an
      uncommon clinical entity known as commotio cordis, sudden death from cardiac
      arrest can occur in young athletes after a blunt blow to the chest, in the
      absence of preexisting cardiovascular disease. We present a case in which the
      clinician's high index of suspicion leads to the diagnosis of acute myocarditis
      in a patient whose sudden cardiac deterioration was initially attributed to the
      result of recent blunt chest trauma. METHODS: A case report and review of
      literature via MEDLINE (1996-2004) search using the key words "myocarditis,"
      "commotio cordis," and "myocardial contusion." RESULTS: A 12-year-old boy was
      admitted with elevated cardiac enzymes and respiratory distress after being hit
      in the chest with a dodgeball. Shortly after admission, the patient developed
      refractory ventricular arrhythmia, which was thought to be the result of blunt
      chest trauma. Further evaluation with endomyocardial biopsy, however,
      demonstrated acute myocarditis as the true etiology, for which the patient
      received immunosuppressive treatment. Unfortunately, the patient eventually
      required cardiac transplantation because of progressive irreversible cardiac
      dysfunction due to myocarditis. CONCLUSIONS: Although acute myocarditis, commotio
      cordis, and myocardial contusion can all present with malignant ventricular
      arrhythmia, other clinical features and approaches to management of each disease
      are very different. This case illustrates the importance of having a broad
      differential diagnosis in mind when presented with a previously healthy child in
      sudden cardiogenic shock.

PMID- 16280950
TI  - Negative-pressure pulmonary edema: a rare complication of upper airway
      obstruction in children.
AB  - Negative-pressure pulmonary edema is a rare but life-threatening complication of
      upper airway obstruction. Because negative-pressure pulmonary edema may occur in
      a large spectrum of pathologies associated with upper airway obstruction,
      awareness of this condition is crucial during daily clinical practice. We report
      a case of negative-pressure pulmonary edema during anesthetic recovery to
      highlight this condition. CASE: A 2-year-old boy was scheduled for orchidopexy
      under general anesthesia. Shortly after an uneventful operation, the patient
      presented airway obstruction. Serious oxygen desaturation and bradycardia ensued,
      during inefficient attempts at positive-pressure ventilation. After emergency
      intubation, copious pink secretions emerged from the airway. Pulmonary edema was
      confirmed by clinical examination, pulse oximetry, and chest radiography. The
      finding of pulmonary edema was resolved within 24 hours after mechanical
      ventilation and positive end-expiratory pressure. The child suffered no sequelae.
      This report highlights the clinical features of negative-pressure pulmonary edema
      and serves as a reminder to the pediatrician who must be able to recognize and
      initiate treatment for conditions that are uncommon but life-threatening.

PMID- 16280952
TI  - Congenital lobar emphysema: tube thoracostomy not the treatment.
AB  - A 23-month-old boy was transferred to our facility after being diagnosed with a
      right-sided pneumothorax in an outlying hospital emergency department. The
      patient's primary complaint was a nonproductive cough and runny nose. Vital signs
      were stable with 98% oxygen saturation by pulse oximetry. Physical examination
      was unremarkable except for diminished breath sounds on the right. Chest x-ray
      revealed a large lucency over the right lung field, yet an intact vascular
      pattern. Computed tomography scan of the chest revealed congenital lobar
      emphysema of the right upper lobe. The pathophysiology, clinical presentation,
      diagnostic evaluation, and management of congenital lobar emphysema are reviewed.

PMID- 16280954
TI  - Dilated cardiomyopathy in a 7-year-old girl.
AB  - Pediatric patients with dilated cardiomyopathy can initially be present for
      medical attention with non-specific and misleading signs and symptoms. We present
      the case of a 7-year-old girl with vague complaints of fever, vomiting, and
      abdominal pain and cardiac murmur on physical exam who progressed to congestive
      heart failure before her dilated cardiomyopathy was diagnosed. Clinicians should
      maintain a high index of suspicion for dilated cardiomyopathy in any patient with
      cardiac murmur and systematic symptoms.

PMID- 16280953
TI  - Tracheoinnominate artery fistula: a rare and often fatal complication of
      indwelling tracheostomy tubes.
AB  - Fistula formation between the innominate artery and the trachea is a rare but
      potentially catastrophic complication after tracheostomy. Although surgery is the
      definitive treatment of tracheoinnominate artery fistula, the responsibility for
      making the proper diagnosis and stabilizing the patient before surgery often
      falls on the personnel in the emergency department. We describe the emergency
      department management of a 14-year-old girl with a tracheoinnominate artery
      fistula. A discussion of the risk factors, diagnostic considerations, and
      emergency department management strategies of tracheoinnominate artery fistula is
      presented.

PMID- 16280955
TI  - Adolescent substance use: brief interventions by emergency care providers.
AB  - Use of tobacco, alcohol and other drugs plays a major role in adolescent
      morbidity and mortality. When under the influence of alcohol or other drugs,
      adolescents are at increased risk for injuries, unprotected sex, or interpersonal
      violence. Alcohol and other drugs are major factors in adolescent deaths,
      contributing to motor vehicle crashes, homicides, and suicides. Adolescents tend
      to have shorter substance use histories therefore they often experience
      emergency/acute care health treatment resulting from substance use related trauma
      and/or overdose. Substance use screening of adolescents who present to an
      Emergency Department (ED) is vitally important. The CRAFFT is a valid and
      reliable screening tool that was developed for use with adolescents. If an
      adolescent screens positive, then the next step is to determine their stage of
      use and readiness for change in preparation for doing a brief intervention.
      Helping patients to recognize the potential relation between their substance use
      and health related consequences, may motivate them to decrease their use for harm
      reduction. Motivational interviewing is an effective, evidence-based approach to
      helping people change their high risk behavior.

PMID- 16280956
TI  - Vaccines in the pipeline.

PMID- 16280958
TI  - Report of the National Consensus Conference on Family Presence During Pediatric
      Cardiopulmonary Resuscitation and Procedures.
AB  - Representatives from 18 national organizations were convened for a conference to
      develop recommendations regarding family presence (FP) during pediatric
      procedures and cardiopulmonary resuscitation. Before the conference, invitees
      were given a questionnaire and provided with current literature regarding FP. A
      modified Delphi process was used to develop consensus, including use of multiple
      questionnaires and breakouts for discussion of specific issues. Participants were
      encouraged to develop consensus recommendations based on the literature and
      discussions. Changes in attitude were tracked with repeat questionnaires. Results
      of the conference were circulated to participants for review and revision.
      Consensus recommendations include (1) consider FP as an option for families
      during pediatric procedures and cardiopulmonary resuscitation, (2) offer FP as an
      option after assessing factors that could adversely affect the interaction, (3)
      if family is not offered the option for FP, document the reasons why, (4) always
      consider the safety of the health care team, (5) develop in-hospital transport
      and transfer policies and procedures for FP, such as family member definition,
      preparation of the family, handling disagreements, and providing support for the
      staff, (6) obtain legal review of policies, (7) include education in FP in all
      core curricula and orientation for health care providers, (8) promote research
      into best methods for education; effects of FP on patients, family, and staff;
      best practices for FP; and legal issues regarding FP, among others. These
      recommendations were approved in concept by the American Academy of Pediatrics
      and the Ambulatory Pediatrics Association.

PMID- 16280960
TI  - ECGs in the ED.

PMID- 16280959
TI  - Case records of Wright State University. Arm disuse during varicella.

PMID- 16280961
TI  - Thrown out of a pickup: multiple injuries.

PMID- 16280964
TI  - Functional dyspepsia: subgroups, history and outcomes.
AB  - Dyspepsia is a symptom complex common both in the population and in clinical
      practice. Persons with dyspeptic symptoms who have not been evaluated are
      considered to have uninvestigated dyspepsia. If, after investigation, no
      structural or biochemical explanation is identified to explain the person's
      symptoms, the diagnosis of functional dyspepsia is made. While substantial
      efforts have been made to provide symptom-based criteria for the diagnosis of
      functional dyspepsia, the etiology and natural history of the disorder remains
      elusive. Population-based studies have often had difficulty distinguishing
      functional dyspepsia from irritable bowel syndrome. Clinically, there is clearly
      substantial overlap and many persons with functional dyspepsia either present
      with symptoms consistent with the irritable bowel syndrome or will develop such
      symptoms at a later date. Even if one can accept functional dyspepsia as an
      entity separate from irritable bowel syndrome, it is clearly a heterogeneous
      disorder. Unfortunately attempts using different strategies to subcategorize
      functional dyspepsia have not made progress with respect to elucidating
      pathophysiology or directing therapy. Importantly, most persons with functional
      dyspepsia experience symptom variability resulting in subgroup reassignment over
      time. Persons presenting with functional dyspepsia will likely remain symptomatic
      over time. Sadly, at the present time, gastroenterologists have little ability to
      predict what those symptoms will be, to understand the mechanism for their
      existence or to offer therapies that offer a reasonable likelihood of success
      based on a pathophysiologic rationale.

PMID- 16280962
TI  - Pediatric emergency medicine: legal briefs.

PMID- 16280963
TI  - The management of univestigated dyspepsia in primary care.
AB  - Dyspepsia is very common in western countries, where 10-40% of the population
      experience upper abdominal pain or discomfort over the course of one year. Mostly
      it is a chronic relapsing problem. Prompt endoscopy is imperative in all patients
      with sinister symptoms (including the first appearance of symptoms after the age
      of 50-55). In other patients endoscopy is unlikely to contribute to medical
      management. In those a ''test and treat'' strategy implying non invasive testing
      for Helicobacter pylori (H. pylori) and treatment of the infection if present
      seems to be the best approach under current conditions (H. pylori prevalence
      among dyspeptics 28-61% in recent studies). If the patient is H. pylori-negative
      and in case of persisting symptoms after successful H. pylori eradication,
      empirical treatment with an antisecretory drug is justified. Endoscopy is
      reserved for those patients in whom this approach fails. With a continuing
      decrease in H. pylori prevalence the accuracy of the used non-invasive H. pylori
      test needs to be high and urea breath tests are to be preferred, the faecal
      antigen test being a reasonable alternative. At a very low prevalence of H.
      pylori in the dyspeptic population (below 10%) non invasive testing for H. pylori
      loses its significance and empirical treatment with an antisecretory drug becomes
      a rational first step. The physician involved in the care for dyspeptic patients
      needs to be aware of the current H. pylori prevalence.

PMID- 16280965
TI  - An urgency to identify and treat chronic hepatitis C.
AB  - The human and monetary costs of chronic hepatitis C and the complications arising
      from this disease, including hepatocellular carcinoma and liver transplantation,
      emphasize the increased urgency to treat hepatitis C virus (HCV)-infected
      patients earlier in the course of their disease. The current standard of
      treatment for patients chronically infected with HCV is combination therapy with
      pegylated interferon plus ribavirin. Among undertreated groups of patients are
      those with persistently normal alanine aminotransferase levels, those coinfected
      with human immunodeficiency virus and HCV, and nonresponders to previous
      treatment with standard interferon. This review summarizes the rationale for
      earlier treatment of chronic HCV infection, as well as evidence showing that
      patients who do not achieve a virologic response on treatment may derive benefit
      from treatment, including improved histologic characteristics and delayed
      progression of disease.

PMID- 16280966
TI  - Diagnostic accuracy of a new rapid urease test (Pronto Dry), before and after
      treatment of Helicobacter pylori infection.
AB  - AIM: The diagnosis of Helicobacter pylori infection can be made easily by the
      rapid urease test during endoscopy. The mainly commercial rapid urease test
      available in routine practice, is in liquid phase, need to be stored at 4 degrees
      C and generally they are not ready to use. Recently a new rapid urease test, the
      Pronto Dry, has been reported to be faster in the final reading, ready to use,
      and it can be stored at room temperature. Aim of the study was to evaluate the
      diagnostic accuracy and the reaction time of Pronto Dry vs liquid phase-rapid
      urease test, before and after treatment of Helicobacter pylori infections.
      METHODS: A total of 315 untreated dyspeptic patients and 323 post-treatment
      patients, were enrolled in this study. At endoscopy, 5 biopsy samples were
      obtained from the antrum and from the corpus for histology; culture and rapid
      urease tests (liquid phase and Dry test). Helicobacter pylori status was defined
      according to European guidelines. Sensitivity and specificity of both rapid
      urease test were assessed at 5, 15, 30 minutes, and 3 and 24 hours after the
      endoscopy. RESULTS: One hundred and eleven out of 315 untreated dyspeptic
      patients were found to be positive for Helicobacter pylori infection, and 56/323
      patients were found still positive after treatment. Sensitivity at 5, 15, 30
      minutes, and 3 and 24 hours in untreated patients were 45%, 71.2%, 81.1%, 90.1%
      and 91.9% respectively for the Pronto Dry vs 6.3%, 31.5%, 51.3%, 78.4% and 90.1%
      for liquid phase rapid urease test. Sensitivity at the same times in not
      eradicated patients were 33.9%, 66.1%, 85.7%, 92.8 and 92.8% respectively for the
      Pronto Dry vs 3.6%, 37.5%, 55.3%73.2%, 92.8% for liquid phase rapid urease test.
      CONCLUSIONS: Pronto Dry showed to have higher sensitivity in pre and post
      treatment setting compared to liquid phase-rapid urease test within 3 hours of
      incubation time.

PMID- 16280967
TI  - Analysis of hepatitis C virus infection among health-care workers: an
      observational study.
AB  - AIM: Hepatitis C virus (HCV) is one of the most common blood-borne pathogens
      transmitted from patients to health care workers (HCWs). The Centers for Disease
      Control and Prevention (CDC) have developed a set of universal precautions to
      help prevent transmission of blood-borne pathogens between patients and HCWs in
      health care settings. HCV infection status among HCWs and proportion of HCWs
      experiencing occupational blood exposure accidents were monitored to assess the
      risk of HCV infection among HCWs at a hospital in Catania, Italy. METHODS: The
      number of HCWs reporting occupational blood exposure accidents during 1999 and
      2004 were compared to examine whether there was any change in the incidence of
      these accidents among 900 HCWs. HCV infection status of these HCWs was also
      analyzed in 1999 and 2004 to determine how many were infected with HCV during
      this time period. RESULTS: HCV infection was detected in 21 out of 900 subjects
      in 1999. The remaining 879 HCWs remained HCV-negative until they were last tested
      in 2004. There was a statistically significant decrease in the number of HCWs
      that experienced occupational blood exposure accidents from 306 in 1999 to 240 in
      2004 (P = 0.001). CONCLUSIONS: The finding that all 871 HCV-negative HCWs
      remained HCV-negative from 1999 until 2004 supports the view that the set of
      universal precautions recommended by the CDC are helpful for preventing HCV
      transmission from patients to HCWs. HCWs must continue following these
      precautions to prevent transmission of HCV and other blood-borne pathogens
      between patients and HCWs in the future.

PMID- 16280968
TI  - Infliximab in refractory severe ulcerative colitis: a case report.

PMID- 16280969
TI  - Cigarette smoking among adults--United States, 2004.
AB  - One of the national health objectives for 2010 is to reduce the prevalence of
      cigarette smoking among adults to < or =12% (objective no. 27-1a). To assess
      progress toward this objective, CDC analyzed self-reported data from the 2004
      National Health Interview Survey (NHIS) sample adult core questionnaire. This
      report describes the results of that analysis, which indicated that, in 2004,
      approximately 20.9% of U.S. adults were current smokers. This prevalence is lower
      than the 21.6% prevalence among U.S. adults in 2003 and is significantly lower
      than the 22.5% prevalence among adults in 2002. The prevalence of heavy smoking
      (> or =25 cigarettes per day) has also declined during the past 11 years, from
      19.1% of smokers in 1993 to 12.1% of smokers in 2004. Tobacco-use prevention and
      control measures appear to be decreasing both the prevalence of cigarette smoking
      and the proportion of heavy smokers, who are at high risk for tobacco-related
      morbidity and mortality. However, to further decrease smoking prevalence among
      adults and to meet the national health objective, effective comprehensive tobacco
      control programs that address both initiation and cessation of smoking should be
      fully implemented in every state and territory.

PMID- 16280970
TI  - State-specific prevalence of cigarette smoking and quitting among adults--United
      States, 2004.
AB  - After stagnating in the early 1990s, cigarette smoking prevalence among adults in
      the United States declined during the late 1990s and early 2000s. In 2002, for
      the first time, more than half of those who had ever smoked had quit smoking. To
      assess the prevalence of current and never cigarette smoking and the proportion
      of ever smokers who had quit smoking, CDC analyzed state/area data from the 2004
      Behavioral Risk Factor Surveillance System (BRFSS). This report summarizes the
      results of that analysis, which indicated substantial variation in current
      cigarette smoking prevalence among 49 states, the District of Columbia (DC),
      Puerto Rico (PR), and the U.S. Virgin Islands (USVI) (range: 9.5%-27.6%). In 44
      states, DC, PR, and USVI, the majority of persons had never smoked. In 34 states,
      PR, and USVI, more than 50% of ever smokers had quit smoking. Effective,
      comprehensive tobacco-use prevention and control programs should be continued and
      expanded to further reduce initiation among young persons and to ensure that
      smokers have access to effective smoking-cessation services, including proactive
      telephone quitline counseling.

PMID- 16280971
TI  - Outbreak of mesotherapy-associated skin reactions--District of Columbia area,
      January-February 2005.
AB  - Mesotherapy is a treatment involving local subcutaneous injections of minute
      quantities of various substances (e.g., vitamins or plant extracts) for cosmetic
      purposes (e.g., fat and wrinkle reduction or body contouring) or relief of
      musculoskeletal pain. In February 2005, the Virginia Department of Health and CDC
      were notified of a cluster of skin reactions unresponsive to antimicrobial
      therapy among patients who had been administered mesotherapy by an unlicensed
      practitioner in the District of Columbia (DC) area. This report 1) summarizes the
      subsequent investigation by CDC and state and local health departments in
      Virginia, Maryland, and DC, which identified prolonged skin reactions in 14
      patients, and 2) provides recommendations for practices related to mesotherapy.
      Patients should accept medical therapy only from licensed practitioners and
      should not permit injection of substances that have not been approved by the Food
      and Drug Administration (FDA). Licensed practitioners should follow safe
      injection practices when practicing mesotherapy and patients should observe that
      safe-injection practices are followed.

PMID- 16280972
TI  - Prevalence of receiving multiple preventive-care services among adults with
      diabetes--United States, 2002-2004.
AB  - An estimated 7% of the U.S. population has diabetes; however, only 70% of these
      persons have had the disease diagnosed. Recommended preventive-care services such
      as annual foot and eye examinations can prevent or delay amputation and
      blindness. Measurement of glycosylated hemoglobin (A1C) two or more times per
      year is important for glycemic control and diabetes management. Three national
      health objectives for 2010 are to increase the proportion of adults with diabetes
      who have an annual dilated eye examination (objective no. 5-13; target: 75%), an
      annual foot examination (objective no. 5-14; target: 75%), and A1C measurements
      at least twice each year (objective no. 5-12; target: 50%). To determine the
      percentage of U.S. adults with diabetes receiving each of these three preventive
      care services and the percentage receiving all three services, CDC analyzed data
      from Behavioral Risk Factor Surveillance System (BRFSS) surveys for 2002-2004.
      This report summarizes the results of that analysis, which determined that four
      in 10 U.S. adults with diabetes reported receiving all three preventive-care
      services; persons with recently diagnosed diabetes and current smokers were least
      likely to receive all three preventive-care services. Increased understanding of
      barriers to receiving multiple preventive-care services and continued
      interventions to ensure their delivery can improve the health status of persons
      with diabetes.

PMID- 16280973
TI  - Good laboratory practices for waived testing sites: survey findings from testing
      sites holding a certificate of waiver under the clinical laboratory improvement
      amendments of 1988 and recommendations for promoting quality testing.
AB  - Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), simple, low
      risk tests can be waived and performed with no routine regulatory oversight in
      physicians' offices and various other locations. Since CLIA was implemented,
      waived testing has steadily increased in the United States. Surveys conducted
      during 1999-2004 by the Centers for Medicare & Medicaid Services and studies
      funded by CDC during 1999-2003 evaluated testing practices in sites holding a
      CLIA Certificate of Waiver (CW). Although study findings indicate CW sites
      generally take measures to perform testing correctly, they raise quality concerns
      about practices that could lead to errors in testing and poor patient outcomes.
      These issues are probably caused, in part, by high personnel turnover rates, lack
      of understanding about good laboratory practices, and inadequate training. This
      report summarizes study findings and provides recommendations developed by the
      Clinical Laboratory Improvement Advisory Committee for conducting quality waived
      testing. These recommendations include considerations before introducing waived
      testing, such as management responsibility for testing, regulatory requirements,
      safety, physical and environmental requirements, benefits and costs, staffing,
      and documentation. They also cover good laboratory practices for the three phases
      of testing: 1) before testing (test ordering and specimen collection), 2) during
      testing (control testing, test performance, and result interpretation and
      recording), and 3) after testing (result reporting, documentation, confirmatory
      testing, and biohazard waste disposal). They are intended to be used by those who
      would benefit from improving their knowledge of good laboratory practices.
      Continued monitoring of waived testing, with a focus on personnel education and
      training, is needed to improve practices and enhance patient safety as waived
      testing continues to increase.

PMID- 16280974
TI  - Pulmonary hypertension surveillance--United States, 1980-2002.
AB  - PROBLEM/CONDITION: Pulmonary hypertension, which is listed on hospital records
      and death certificates as either primary (i.e., idiopathic) pulmonary
      hypertension or pulmonary hypertension secondary to another underlying condition
      or disease, is considered rare amongst the U.S. population. Limited reports have
      been published regarding surveillance data for this debilitating and often fatal
      condition. REPORTING PERIOD COVERED: 1980-2002. DESCRIPTION OF SYSTEMS: This
      report summarizes mortality data from the National Vital Statistic System (NVSS)
      and hospital discharge data from the National Hospital Discharge Survey (NHDS)
      for 1980-2002 and Medicare hospital claims data for 1990-2002. NVSS, maintained
      by CDC's National Center for Health Statistics (NCHS), compiles multiple cause of
      death information from official death certificates filed in the United States.
      NHDS, also conducted annually by NCHS, includes information on discharges from a
      sample of nonfederal, short-stay hospitals. Annual hospital claims and enrollment
      data for all Medicare beneficiaries aged > or =65 years are provided by the
      Center for Medicare and Medicaid Services. Because pulmonary hypertension might
      be reported secondary to other diseases, this report presents data for pulmonary
      hypertension as any contributing cause of death or any-listed hospital diagnosis.
      Since 1980, the numbers of deaths and hospitalizations, death rates, and
      hospitalization rates have increased for pulmonary hypertension, particularly
      among women and older adults. During 1980-2000, death rates were higher for men
      than women; however, by 2002, no difference in rate was observed because of
      increasing death rates among women and declining death rates among men.
      Hospitalization rates were higher for men than for women until 1995; after 1995,
      higher rates were observed among women. Death rates since 1985 and Medicare
      hospitalization rates throughout the reporting period 1990-2002 have been higher
      for blacks than for whites. In addition, two distinct geographic clusters were
      observed for the highest hospitalization rates in the Medicare population and the
      highest death rates for pulmonary hypertension, in the western United States and
      in the Appalachian region. INTERPRETATION: Increases in mortality from and
      hospitalization for pulmonary hypertension might reflect increased physician
      awareness and changes in diagnosing and reporting this chronic disease. Although
      pulmonary hypertension historically has been considered a disease of women of
      childbearing age, it affects all ages and racial populations. Older women
      represent the majority of patients and decedents with this condition. More
      research is needed concerning cause, prevention, and treatment of pulmonary
      hypertension. Public health initiatives should include increasing physician
      awareness that early detection is needed to initiate prompt, effective disease
      management. Additional epidemiologic initiatives also are needed to ascertain
      prevalence and incidence of various pulmonary hypertension disease entities such
      as pulmonary arterial hypertension.

PMID- 16280975
TI  - Lack of fiber cell induction stops normal growth of rat lenses in organ culture.
AB  - PURPOSE: Lens organ culture has been widely used as a model system for studying
      cataract induction and prevention. While rat lenses remain transparent and viable
      for a week or longer in culture, they do not increase in weight. This study was
      undertaken to determine what accounts for the lack of weight increase. METHODS:
      Lenses from 4-week-old Sprague-Dawley rats were cultured using standard methods.
      Histological analysis was performed on sections from methacrylate embedded
      tissue. 35S-labeled amino acids were used to metabolically label lenses in
      culture for the purpose of analyzing protein synthesis. BrdU labeling was used to
      assess synthesis of DNA in vivo and in vitro. RESULTS: Lenses from young, rapidly
      growing rats do not increase in weight after being put into organ culture.
      Protein synthesis continues in the cultured lenses although at decreased levels
      as time in culture increases. Lens epithelial cells continue to synthesize DNA as
      indicated by BrdU labeling, however, the normal migration of epithelial cells
      from the proliferative zone to the equator does not occur in culture. In the
      cultured lens, the shape of the lens bow gradually changes, becoming compressed
      towards the capsule. CONCLUSIONS: The differentiation of lens epithelial cells
      into fibers is arrested in the cultured lens; consequently lenses in organ
      culture do not grow normally.

PMID- 16280976
TI  - Anti-thyroid methimazole in an acidosis-induced retinopathy rat model of
      retinopathy of prematurity.
AB  - PURPOSE: Methimazole (MMI), an anti-thyroid drug known to reduce serum levels of
      L-thyroxine (T4) and insulin-like growth factor-1 (IGF-1), has been previously
      reported to increase the incidence of neovascularization (NV) in an oxygen
      induced retinopathy (OIR) model of retinopathy of prematurity (ROP) in rats. We
      investigated the effect of MMI on the incidence and severity of NV in a non
      oxygen-induced model of ROP, acidosis-induced retinopathy (AIR). METHODS: Newborn
      Sprague Dawley rats were raised in expanded litters of 25 in room air for four or
      ten days under one of the two following conditions: (1) Our established model of
      AIR (acidosis via NH4Cl gavage (10 mmol/kg) twice daily from days 2 to 7,
      followed by two days of recovery) or (2) MMI (given as a 0.1% solution to nursing
      mothers) in the above AIR model. Left eyes were fixed, and retinas were dissected
      and ADPase-stained. Flat mounted retinas were graded in a masked manner for
      presence and severity of NV, and retinal vascular areas were quantified. Serum
      IGF-1 and T4 concentrations were measured by radioimmunoassay on days 4 and 10.
      Arterial blood pH measurements were performed on day 4. RESULTS: The incidence
      and severity of NV were similar between AIR and MMI-AIR rats (incidence: 24% and
      33%). Serum IGF-1 concentrations in 10 day MMI-AIR rats were significantly lower
      than untreated non-acidotic controls (medians: 158 ng/ml and 207 ng/ml; p=0.03).
      Serum IGF-1 concentrations were similar between 10 day AIR rats and untreated non
      acidotic controls (medians: 189 ng/ml and 207 ng/ml; p>0.9). CONCLUSIONS: MMI
      does not increase the incidence or severity of NV in an AIR neonatal rat model of
      ROP. Although serum IGF-1 has been considered permissive for NV in immature
      retinas, supranormal concentrations of serum IGF-1 may not be necessary for
      abnormal retinal angiogenesis. Further studies are warranted on the roles of
      serum IGF-1 and L-thyroxine in the pathogenesis of ROP.

PMID- 16280977
TI  - Myocilin mt1 promoter polymorphism in Turkish patients with primary open angle
      glaucoma.
AB  - PURPOSE: To evaluate the association of the myocilin gene promoter variant 
      1000C>G (MYOC.mt1) with primary open angle glaucoma (POAG) and its possible role
      on the phenotype and the severity of glaucoma in Turkish patients. METHODS:
      Eighty eight POAG patients and 123 healthy subjects were included in the study.
      All subjects were genotyped by PCR-RFLP. Allele and genotype frequencies between
      healthy subjects and glaucoma patients were compared by the chi2 test. The age at
      diagnosis, the age at inclusion, the maximum IOP at diagnosis and the number of
      antiglaucomatous medications were compared between MYOC.mt1 carriers and non
      carriers using the Student's t-test; C/D ratio, mean deviation (MD), and pattern
      standard deviation values were compared with the Mann-Whitney U-test. Statistical
      significance was defined as p<0.05. RESULTS: MYOC.mt1 genotype and allele
      frequencies did not differ in POAG and healthy subjects (p=0.204 and p=0.083,
      respectively). In the control group, 17.1% of the subjects were MYOC.mt1
      carriers, while 27.3% of the POAG patients were MYOC.mt1 carriers (p=0.107). The
      odds ratio for CG was 1.859 (95% CI: 0.9-3.7; p=0.084) and for GG 1.594 (95% CI:
      0.31-8.13; p=0.575). The phenotype variables were quite similar in MYOC.mt1
      carriers and non-carriers. Gender by itself or with the MYOC.mt1 did not have any
      effect on IOP, C/D ratio, or MD values (univariate analysis of variance, p>0.05).
      No significant difference was found in the distribution of genotypes between
      different stages of glaucoma groups (p=0.93). CONCLUSIONS: Our results suggest
      that in our Turkish glaucoma patients, MYOC.mt1 is not a risk factor for the
      development of POAG and is not associated with the phenotype and severity of
      glaucoma.

PMID- 16280978
TI  - Sequence variations in the retinal fascin FSCN2 gene in a Spanish population with
      autosomal dominant retinitis pigmentosa or macular degeneration.
AB  - PURPOSE: Only one mutation in the retinal fascin gene (FSCN2) has so far been
      associated with autosomal dominant retinitis pigmentosa (adRP) and macular
      dystrophy (adMD), in a Japanese population. Our study was designed to identify
      mutations in the FSCN2 gene among Spanish persons with adRP or adMD. METHODS:
      Denaturing gradient gel electrophoresis and direct genomic sequencing were used
      to evaluate the complete coding region and flanking intronic sequences of the
      FSCN2 gene for mutations in 150 unrelated adRP and 15 adMD index patients, and in
      50 sporadic cases of retinitis pigmentosa, together with 50 controls. Ophthalmic
      and electrophysiological examination of retinitis pigmentosa patients and their
      relatives was carried out according to pre-existing protocols. RESULTS: Sixteen
      nucleotide substitutions were detected in the coding sequence of the index
      patients. Nine of these, His7Tyr, Ala122Thr, Ser126Phe, His138Tyr, Arg149Gln,
      Ala240Thr, Ala323Thr, Asn331His, and Phe367Leu are missense mutations, one is a
      nonsense mutation (Lys302Stop), and six are silent mutations. Co-segregation of
      the mutations in the families showed no direct relation between mutation and
      disease. CONCLUSIONS: The photoreceptor-specific FSCN2 gene showed a relatively
      high number of sequence variations. The mutation 208delG in FSCN2, the only
      mutation so far associated with adRP or adMD, and which presumably causes a null
      allele, was not detected in these Spanish families. The nonsense mutation,
      Lys302Stop, detected in one adRP Spanish family is not the cause of the disease.
      These findings support the fact that the kind and frequency of the mutations
      depend on the ethnic population.

PMID- 16280979
TI  - Role of the CCL2/MCP-1 -2518A>G gene polymorphism in HLA-B27 associated uveitis.
AB  - PURPOSE: Acute anterior uveitis (AAU) is the most common form of uveitis. Up to
      50% of patients with AAU are HLA-B27 positive. Since HLA B27 itself plays only a
      minor role in the overall genetic background, other genetic variants are likely
      to contribute to the susceptibility to AAU. The chemokine (C-C motif) ligand 2
      (CCL2) gene, coding for monocyte chemoattractant protein-1 (MCP-1), a chemotactic
      cytokine, is involved in the induction of uveitis. A CCL2 gene polymorphism,
      which is characterized by an A>G substitution at nucleotide -2518 in the promoter
      region of CCL2 has been previously shown to affect MCP-1 synthesis. The purpose
      of the present study was to investigate a hypothesized association between this
      genetic variant and the presence of HLA-B27 associated AAU. METHODS: The study
      group comprised 114 patients with HLA-B27 associated AAU. One hundred and eleven
      healthy HLA-B27 positive individuals served as the HLA-B27 positive control
      group, whereas 81 healthy HLA-B27 negative individuals served as a HLA-B27
      negative control group. Genotyping for the CCL2 -2518A>G polymorphism was
      performed by polymerase chain reaction. RESULTS: Carriers of a CCL2 -2518G allele
      were found significantly more often in patients with HLA-B27 associated AAU than
      among HLA-B27 positive controls (49.2% and 31.5%, respectively; odds ratio 2.1;
      95% confidence interval 1.2-3.6; p=0.007). CONCLUSIONS: Our data suggest that the
      CCL2 -2518A>G polymorphism may play a role in HLA-B27 associated acute anterior
      uveitis.

PMID- 16280980
TI  - Cerebral hyperperfusion after carotid endarterectomy is associated with
      preoperative hemodynamic impairment and intraoperative cerebral ischemia.
AB  - The aim of this study was to investigate whether postoperative hyperperfusion is
      associated with preoperative cerebral hemodynamic impairment due to chronic
      ischemia and with acute cerebral ischemia during clamping of the internal carotid
      artery (ICA) during carotid endarterectomy (CEA). Transcranial cerebral oxygen
      saturation (SO2) was monitored intraoperatively using near-infrared spectroscopy
      in 89 patients undergoing CEA for ipsilateral ICA stenosis (>70%). Cerebral blood
      flow (CBF) and cerebrovascular reactivity (CVR) to acetazolamide were also
      measured using single photon emission computed tomography (SPECT) before CEA. In
      addition, CBF was measured immediately after CEA and on the third postoperative
      day. Hyperperfusion (CBF increase>100% compared with preoperative values) was
      observed immediately after CEA in 10 of 18 patients (56%) with reduced
      preoperative CVR. Also, post-CEA hyperperfusion was observed in nine of 16
      patients (56%) whose SO2 during clamping of the ICA decreased to less than 90% of
      the preclamping value. Logistic regression analysis showed that reduced
      preoperative CVR and reduced SO2 during ICA clamping were significant independent
      predictors of the development of hyperperfusion immediately after CEA. In fact,
      all patients with reduced preoperative CVR and reduced SO2 during ICA clamping
      developed post-CEA hyperperfusion, and two of these patients developed cerebral
      hyperperfusion syndrome. These data suggest that development of cerebral
      hyperperfusion after CEA is associated with preoperative hemodynamic impairment
      and intraoperative cerebral ischemia.

PMID- 16280981
TI  - Wnt-Ryk signalling mediates medial-lateral retinotectal topographic mapping.
AB  - Computational modelling has suggested that at least two counteracting forces are
      required for establishing topographic maps. Ephrin-family proteins are required
      for both anterior-posterior and medial-lateral topographic mapping, but the
      opposing forces have not been well characterized. Wnt-family proteins are
      recently discovered axon guidance cues. We find that Wnt3 is expressed in a
      medial-lateral decreasing gradient in chick optic tectum and mouse superior
      colliculus. Retinal ganglion cell (RGC) axons from different dorsal-ventral
      positions showed graded and biphasic response to Wnt3 in a concentration
      dependent manner. Wnt3 repulsion is mediated by Ryk, expressed in a ventral-to
      dorsal decreasing gradient, whereas attraction of dorsal axons at lower Wnt3
      concentrations is mediated by Frizzled(s). Overexpression of Wnt3 in the lateral
      tectum repelled the termination zones of dorsal RGC axons in vivo. Expression of
      a dominant-negative Ryk in dorsal RGC axons caused a medial shift of the
      termination zones, promoting medially directed interstitial branches and
      eliminating laterally directed branches. Therefore, a classical morphogen, Wnt3,
      acting as an axon guidance molecule, plays a role in retinotectal mapping along
      the medial-lateral axis, counterbalancing the medial-directed EphrinB1-EphB
      activity.

PMID- 16280982
TI  - Functional waters in intraprotein proton transfer monitored by FTIR difference
      spectroscopy.
AB  - Much progress has been made in our understanding of water molecule reactions on
      surfaces, proton solvation in gas-phase water clusters and proton transfer
      through liquids. Compared with our advanced understanding of these physico
      chemical systems, much less is known about individual water molecules and their
      cooperative behaviour in heterogeneous proteins during enzymatic reactions. Here
      we use time-resolved Fourier transform infrared spectroscopy (trFTIR) and in situ
      H2(18)O/H2(16)O exchange FTIR to determine how the membrane protein
      bacteriorhodopsin uses the interplay among strongly hydrogen-bonded water
      molecules, a water molecule with a dangling hydroxyl group and a protonated water
      cluster to transfer protons. The precise arrangement of water molecules in the
      protein matrix results in a controlled Grotthuss proton transfer, in contrast to
      the random proton migration that occurs in liquid water. Our findings support the
      emerging paradigm that intraprotein water molecules are as essential for
      biological functions as amino acids.

PMID- 16280984
TI  - Neuroscience: rewiring the adult brain.
AB  - Any analysis of plastic reorganization at a neuronal locus needs a veridical
      measure of changes in the functional output--that is, spiking responses of the
      neurons in question. In a study of the effect of retinal lesions on adult primary
      visual cortex (V1), Smirnakis et al. propose that there is no cortical
      reorganization. Their results are based, however, on BOLD (blood-oxygen-level
      dependent) fMRI (functional magnetic resonance imaging), which provides an
      unreliable gauge of spiking activity. We therefore question their criterion for
      lack of plasticity, particularly in the light of the large body of earlier work
      that demonstrates cortical plasticity.

PMID- 16280988
TI  - A less toxic solution.

PMID- 16280989
TI  - DARPA dreaming.

PMID- 16280990
TI  - Flu in circulation.

PMID- 16280992
TI  - Deadly flu virus can be sent through the mail.

PMID- 16280993
TI  - Far East lays plans to be stem-cell hotspot.

PMID- 16280996
TI  - Boeing strike leaves satellites stranded on launch pad.

PMID- 16280997
TI  - Bush buries US bunker-buster project.

PMID- 16280994
TI  - Researchers break the rules in frustration at review boards.

PMID- 16280998
TI  - Antigravity craft slips past patent officers.

PMID- 16280999
TI  - Congress attacked over species bill.

PMID- 16281001
TI  - Animal testing: more than a cosmetic change.

PMID- 16281002
TI  - Linguistics: tongue tied.

PMID- 16281003
TI  - Psychiatric disease: all in the mind of a mouse.

PMID- 16281004
TI  - Path to approval proves rocky for copycat biodrugs.

PMID- 16281008
TI  - Biodiversity: journals must take a broader view.

PMID- 16281007
TI  - Biodiversity: saving Florida panther makes sense.

PMID- 16281009
TI  - Biodiversity needs the help of global change managers, not museum-keepers.

PMID- 16281019
TI  - Neurobiology: triggers for channel opening.

PMID- 16281020
TI  - Materials Science: erasing electron mass.

PMID- 16281022
TI  - Seismology: the start of something big?

PMID- 16281023
TI  - Circadian rhythms: clock coordination.

PMID- 16281021
TI  - Microbiology: RAMP resistance.

PMID- 16281025
TI  - Gravitational tractor for towing asteroids.
AB  - We present a design concept for a spacecraft that can controllably alter the
      trajectory of an Earth-threatening asteroid by using gravity as a towline. The
      spacecraft hovers near the asteroid, with its thrusters angled outwards so that
      the exhaust does not impinge on the surface. This proposed deflection method is
      insensitive to the structure, surface properties and rotation state of the
      asteroid.

PMID- 16281026
TI  - Green chemistry: biodiesel made with sugar catalyst.
AB  - The production of diesel from vegetable oil calls for an efficient solid catalyst
      to make the process fully ecologically friendly. Here we describe the preparation
      of such a catalyst from common, inexpensive sugars. This high-performance
      catalyst, which consists of stable sulphonated amorphous carbon, is recyclable
      and its activity markedly exceeds that of other solid acid catalysts tested for
      'biodiesel' production.

PMID- 16281027
TI  - Pathogenic bacteria induce aversive olfactory learning in Caenorhabditis elegans.
AB  - Food can be hazardous, either through toxicity or through bacterial infections
      that follow the ingestion of a tainted food source. Because learning about food
      quality enhances survival, one of the most robust forms of olfactory learning is
      conditioned avoidance of tastes associated with visceral malaise. The nematode
      Caenorhabditis elegans feeds on bacteria but is susceptible to infection by
      pathogenic bacteria in its natural environment. Here we show that C. elegans
      modifies its olfactory preferences after exposure to pathogenic bacteria,
      avoiding odours from the pathogen and increasing its attraction to odours from
      familiar nonpathogenic bacteria. Particular bacteria elicit specific changes in
      olfactory preferences that are suggestive of associative learning. Exposure to
      pathogenic bacteria increases serotonin in ADF chemosensory neurons by
      transcriptional and post-transcriptional mechanisms. Serotonin functions through
      MOD-1, a serotonin-gated chloride channel expressed in sensory interneurons, to
      promote aversive learning. An increase in serotonin may represent the negative
      reinforcing stimulus in pathogenic infection.

PMID- 16281028
TI  - Subunit arrangement and function in NMDA receptors.
AB  - Excitatory neurotransmission mediated by NMDA (N-methyl-D-aspartate) receptors is
      fundamental to the physiology of the mammalian central nervous system. These
      receptors are heteromeric ion channels that for activation require binding of
      glycine and glutamate to the NR1 and NR2 subunits, respectively. NMDA receptor
      function is characterized by slow channel opening and deactivation, and the
      resulting influx of cations initiates signal transduction cascades that are
      crucial to higher functions including learning and memory. Here we report crystal
      structures of the ligand-binding core of NR2A with glutamate and that of the NR1
      NR2A heterodimer with glutamate and glycine. The NR2A-glutamate complex defines
      the determinants of glutamate and NMDA recognition, and the NR1-NR2A heterodimer
      suggests a mechanism for ligand-induced ion channel opening. Analysis of the
      heterodimer interface, together with biochemical and electrophysiological
      experiments, confirms that the NR1-NR2A heterodimer is the functional unit in
      tetrameric NMDA receptors and that tyrosine 535 of NR1, located in the subunit
      interface, modulates the rate of ion channel deactivation.

PMID- 16281029
TI  - Simulation of equatorial and high-latitude jets on Jupiter in a deep convection
      model.
AB  - The bands of Jupiter represent a global system of powerful winds. Broad eastward
      equatorial jets are flanked by smaller-scale, higher-latitude jets flowing in
      alternating directions. Jupiter's large thermal emission suggests that the winds
      are powered from within, but the zonal flow depth is limited by increasing
      density and electrical conductivity in the molecular hydrogen-helium atmosphere
      towards the centre of the planet. Two types of planetary flow models have been
      explored: shallow-layer models reproduce multiple high-latitude jets, but not the
      equatorial flow system, and deep convection models only reproduce an eastward
      equatorial jet with two flanking neighbours. Here we present a numerical model of
      three-dimensional rotating convection in a relatively thin spherical shell that
      generates both types of jets. The simulated flow is turbulent and quasi-two
      dimensional and, as observed for the jovian jets, simulated jet widths follow
      Rhines' scaling theory. Our findings imply that Jupiter's latitudinal transition
      in jet width corresponds to a separation between the bottom-bounded flow
      structures in higher latitudes and the deep equatorial flows.

PMID- 16281030
TI  - Two-dimensional gas of massless Dirac fermions in graphene.
AB  - Quantum electrodynamics (resulting from the merger of quantum mechanics and
      relativity theory) has provided a clear understanding of phenomena ranging from
      particle physics to cosmology and from astrophysics to quantum chemistry. The
      ideas underlying quantum electrodynamics also influence the theory of condensed
      matter, but quantum relativistic effects are usually minute in the known
      experimental systems that can be described accurately by the non-relativistic
      Schrodinger equation. Here we report an experimental study of a condensed-matter
      system (graphene, a single atomic layer of carbon) in which electron transport is
      essentially governed by Dirac's (relativistic) equation. The charge carriers in
      graphene mimic relativistic particles with zero rest mass and have an effective
      'speed of light' c* approximately 10(6) m s(-1). Our study reveals a variety of
      unusual phenomena that are characteristic of two-dimensional Dirac fermions. In
      particular we have observed the following: first, graphene's conductivity never
      falls below a minimum value corresponding to the quantum unit of conductance,
      even when concentrations of charge carriers tend to zero; second, the integer
      quantum Hall effect in graphene is anomalous in that it occurs at half-integer
      filling factors; and third, the cyclotron mass m(c) of massless carriers in
      graphene is described by E = m(c)c*2. This two-dimensional system is not only
      interesting in itself but also allows access to the subtle and rich physics of
      quantum electrodynamics in a bench-top experiment.

PMID- 16281031
TI  - Experimental observation of the quantum Hall effect and Berry's phase in
      graphene.
AB  - When electrons are confined in two-dimensional materials, quantum-mechanically
      enhanced transport phenomena such as the quantum Hall effect can be observed.
      Graphene, consisting of an isolated single atomic layer of graphite, is an ideal
      realization of such a two-dimensional system. However, its behaviour is expected
      to differ markedly from the well-studied case of quantum wells in conventional
      semiconductor interfaces. This difference arises from the unique electronic
      properties of graphene, which exhibits electron-hole degeneracy and vanishing
      carrier mass near the point of charge neutrality. Indeed, a distinctive half
      integer quantum Hall effect has been predicted theoretically, as has the
      existence of a non-zero Berry's phase (a geometric quantum phase) of the electron
      wavefunction--a consequence of the exceptional topology of the graphene band
      structure. Recent advances in micromechanical extraction and fabrication
      techniques for graphite structures now permit such exotic two-dimensional
      electron systems to be probed experimentally. Here we report an experimental
      investigation of magneto-transport in a high-mobility single layer of graphene.
      Adjusting the chemical potential with the use of the electric field effect, we
      observe an unusual half-integer quantum Hall effect for both electron and hole
      carriers in graphene. The relevance of Berry's phase to these experiments is
      confirmed by magneto-oscillations. In addition to their purely scientific
      interest, these unusual quantum transport phenomena may lead to new applications
      in carbon-based electronic and magneto-electronic devices.

PMID- 16281032
TI  - A record of Permian subaqueous vent activity in southeastern Brazil.
AB  - The remarkable occurrence of more than 4,500 conical siliceous mounds in an area
      of less than 1.5 square kilometres has been reported in the Parana basin, near
      Anhembi, Sao Paulo, in southeastern Brazil. These structures, which are up to two
      metres high, are thought to have been formed at the margin of a very shallow,
      broad but waning internal sea, and it was originally suggested that they are
      stromatolites. Yet their restricted occurrence, unusual abundance and nearly pure
      siliceous composition have never been satisfactorily explained by this
      hypothesis. Here we report field and laboratory observations on their shape,
      construction, composition and mineralogy. On the basis of our data we suggest
      that the conical mounds are the result of subaqueous Late Permian vent activity
      in southwestern Gondwana. The present siliceous cone field differs considerably
      from other Palaeozoic siliceous hot spring deposits, such as those at Rhynie,
      Scotland, and the Drummond basin, Australia, and therefore represents an unusual
      occurrence of vent activity.

PMID- 16281033
TI  - The deterministic nature of earthquake rupture.
AB  - Understanding the earthquake rupture process is central to our understanding of
      fault systems and earthquake hazards. Multiple hypotheses concerning the nature
      of fault rupture have been proposed but no unifying theory has emerged. The
      conceptual hypothesis most commonly cited is the cascade model for fault rupture.
      In the cascade model, slip initiates on a small fault patch and continues to
      rupture further across a fault plane as long as the conditions are favourable.
      Two fundamental implications of this domino-like theory are that small
      earthquakes begin in the same manner as large earthquakes and that the rupture
      process is not deterministic--that is, the size of the earthquake cannot be
      determined until the cessation of rupture. Here we show that the frequency
      content of radiated seismic energy within the first few seconds of rupture scales
      with the final magnitude of the event. We infer that the magnitude of an
      earthquake can therefore be estimated before the rupture is complete. This
      finding implies that the rupture process is to some degree deterministic and has
      implications for the physics of the rupture process.

PMID- 16281034
TI  - Single origin of a pan-Pacific bird group and upstream colonization of
      Australasia.
AB  - Oceanic islands have long served as natural laboratories for understanding the
      diversification of life. In particular, the many thousands of islands spanning
      the tropical Pacific support an unparalleled array of terrestrial communities
      whose patterns of diversity contributed fundamental insights to the development
      of classical speciation and biogeographic theory. Much of this work is founded on
      an assumption derived from traditional taxonomic approaches, namely that faunas
      on these widely separated archipelagos stem from a simple one-way, downstream
      flow of colonists from continents to islands. Here we show, with the use of
      molecular phylogenetic data from one of the original bird families used to
      justify this assumption, that a diverse array of endemic island genera and
      species are the product of a single radiation that diversified across all major
      Pacific archipelagos in a non-stepping-stone fashion, and recently recolonized
      continental areas. The geographic scope and lineage-specific approach of this
      study reveal evolutionary patterns long obscured by traditional taxonomic surveys
      and indicate that widely dispersed archipelagos can be sources of biological
      diversity.

PMID- 16281035
TI  - A mutation accumulation assay reveals a broad capacity for rapid evolution of
      gene expression.
AB  - Mutation is the ultimate source of biological diversity because it generates the
      variation that fuels evolution. Gene expression is the first step by which an
      organism translates genetic information into developmental change. Here we
      estimate the rate at which mutation produces new variation in gene expression by
      measuring transcript abundances across the genome during the onset of
      metamorphosis in 12 initially identical Drosophila melanogaster lines that
      independently accumulated mutations for 200 generations. We find statistically
      significant mutational variation for 39% of the genome and a wide range of
      variability across corresponding genes. As genes are upregulated in development
      their variability decreases, and as they are downregulated it increases,
      indicating that developmental context affects the evolution of gene expression. A
      strong correlation between mutational variance and environmental variance shows
      that there is the potential for widespread canalization. By comparing the
      evolutionary rates that we report here with differences between species, we
      conclude that gene expression does not evolve according to strictly neutral
      models. Although spontaneous mutations have the potential to generate abundant
      variation in gene expression, natural variation is relatively constrained.

PMID- 16281036
TI  - Fruitless specifies sexually dimorphic neural circuitry in the Drosophila brain.
AB  - The Drosophila fruitless (fru) gene product Fru has been postulated to be a
      neural sex determination factor that directs development of the central nervous
      system (CNS), thereby producing male-typical courtship behaviour and inducing
      male-specific muscle. Male-specific Fru protein is expressed in small groups of
      neurons scattered throughout the CNS of male, but not female, Drosophila.
      Collectively, these observations suggest that Fru 'masculinizes' certain neurons,
      thereby establishing neural substrates for male-typical behaviour. However,
      specific differences between neurons resulting from the presence or absence of
      Fru are unknown. Previous studies have suggested that Fru might result in sexual
      differences in the CNS at the functional level, as no overt sexual dimorphism in
      CNS structure was discernible. Here we identify a subset of fru-expressing
      interneurons in the brain that show marked sexual dimorphism in their number and
      projection pattern. We also demonstrate that Fru supports the development of
      neurons with male-specific dendritic fields, which are programmed to die during
      female development as a result of the absence of Fru. Thus, Fru expression can
      produce a male-specific neural circuit, probably used during heterosexual
      courtship, by preventing cell death in identifiable neurons.

PMID- 16281037
TI  - Suppression of Polycomb group proteins by JNK signalling induces
      transdetermination in Drosophila imaginal discs.
AB  - During the regeneration of Drosophila imaginal discs, cellular identities can
      switch fate in a process known as transdetermination. For leg-to-wing
      transdetermination, the underlying mechanism involves morphogens such as Wingless
      that, when activated outside their normal context, induce ectopic expression of
      the wing-specific selector gene vestigial. Polycomb group (PcG) proteins maintain
      cellular fates by controlling the expression patterns of homeotic genes and other
      developmental regulators. Here we report that transdetermination events are
      coupled to PcG regulation. We show that the frequency of transdetermination is
      enhanced in PcG mutant flies. Downregulation of PcG function, as monitored by the
      reactivation of a silent PcG-regulated reporter gene, is observed in
      transdetermined cells. This downregulation is directly controlled by the Jun
      amino-terminal kinase (JNK) signalling pathway, which is activated in cells
      undergoing regeneration. Accordingly, transdetermination frequency is reduced in
      a JNK mutant background. This regulatory interaction also occurs in mammalian
      cells, indicating that the role of this signalling cascade in remodelling
      cellular fates may be conserved.

PMID- 16281038
TI  - A resetting signal between Drosophila pacemakers synchronizes morning and evening
      activity.
AB  - The biochemical machinery that underlies circadian rhythms is conserved among
      animal species and drives self-sustained molecular oscillations and functions,
      even within individual asynchronous tissue-culture cells. Yet the rhythm
      generating neural centres of higher eukaryotes are usually composed of
      interconnected cellular networks, which contribute to robustness and synchrony as
      well as other complex features of rhythmic behaviour. In mammals, little is known
      about how individual brain oscillators are organized to orchestrate a complex
      behavioural pattern. Drosophila is arguably more advanced from this point of
      view: we and others have recently shown that a group of adult brain clock neurons
      expresses the neuropeptide PDF and controls morning activity (small LN(v) cells;
      M-cells), whereas another group of clock neurons controls evening activity (CRY+,
      PDF- cells; E-cells). We have generated transgenic mosaic animals with different
      circadian periods in morning and evening cells. Here we show, by behavioural and
      molecular assays, that the six canonical groups of clock neurons are organized
      into two separate neuronal circuits. One has no apparent effect on locomotor
      rhythmicity in darkness, but within the second circuit the molecular and
      behavioural timing of the evening cells is determined by morning-cell properties.
      This is due to a daily resetting signal from the morning to the evening cells,
      which run at their genetically programmed pace between consecutive signals. This
      neural circuit and oscillator-coupling mechanism ensures a proper relationship
      between the timing of morning and evening locomotor activity.

PMID- 16281039
TI  - Principal pathway coupling agonist binding to channel gating in nicotinic
      receptors.
AB  - Synaptic receptors respond to neurotransmitters by opening an intrinsic ion
      channel in the final step in synaptic transmission. How binding of the
      neurotransmitter is conveyed over the long distance to the channel remains a
      central question in neurobiology. Here we delineate a principal pathway that
      links neurotransmitter binding to channel gating by using a structural model of
      the Torpedo acetylcholine receptor at 4-A resolution, recordings of currents
      through single receptor channels and determinations of energetic coupling between
      pairs of residues. We show that a pair of invariant arginine and glutamate
      residues in each receptor alpha-subunit electrostatically links peripheral and
      inner beta-sheets from the binding domain and positions them to engage with the
      channel. The key glutamate and flanking valine residues energetically couple to
      conserved proline and serine residues emerging from the top of the channel
      forming alpha-helix, suggesting that this is the point at which the binding
      domain triggers opening of the channel. The series of interresidue couplings
      identified here constitutes a primary allosteric pathway that links
      neurotransmitter binding to channel gating.

PMID- 16281040
TI  - Cis-trans isomerization at a proline opens the pore of a neurotransmitter-gated
      ion channel.
AB  - 5-hydroxytryptamine type 3 (5-HT3) receptors are members of the Cys-loop receptor
      superfamily. Neurotransmitter binding in these proteins triggers the opening
      (gating) of an ion channel by means of an as-yet-uncharacterized conformational
      change. Here we show that a specific proline (Pro 8*), located at the apex of the
      loop between the second and third transmembrane helices (M2-M3), can link binding
      to gating through a cis-trans isomerization of the protein backbone. Using
      unnatural amino acid mutagenesis, a series of proline analogues with varying
      preference for the cis conformer was incorporated at the 8* position. Proline
      analogues that strongly favour the trans conformer produced non-functional
      channels. Among the functional mutants there was a strong correlation between the
      intrinsic cis-trans energy gap of the proline analogue and the activation of the
      channel, suggesting that cis-trans isomerization of this single proline provides
      the switch that interconverts the open and closed states of the channel.
      Consistent with this proposal, nuclear magnetic resonance studies on an M2-M3
      loop peptide reveal two distinct, structured forms. Our results thus confirm the
      structure of the M2-M3 loop and the critical role of Pro 8* in the 5-HT3
      receptor. In addition, they suggest that a molecular rearrangement at Pro 8* is
      the structural mechanism that opens the receptor pore.

PMID- 16281042
TI  - Possible solar origin of the 1,470-year glacial climate cycle demonstrated in a
      coupled model.
AB  - Many palaeoclimate records from the North Atlantic region show a pattern of rapid
      climate oscillations, the so-called Dansgaard-Oeschger events, with a quasi
      periodicity of approximately 1,470 years for the late glacial period. Various
      hypotheses have been suggested to explain these rapid temperature shifts,
      including internal oscillations in the climate system and external forcing,
      possibly from the Sun. But whereas pronounced solar cycles of approximately 87
      and approximately 210 years are well known, a approximately 1,470-year solar
      cycle has not been detected. Here we show that an intermediate-complexity climate
      model with glacial climate conditions simulates rapid climate shifts similar to
      the Dansgaard-Oeschger events with a spacing of 1,470 years when forced by
      periodic freshwater input into the North Atlantic Ocean in cycles of
      approximately 87 and approximately 210 years. We attribute the robust 1,470-year
      response time to the superposition of the two shorter cycles, together with
      strongly nonlinear dynamics and the long characteristic timescale of the
      thermohaline circulation. For Holocene conditions, similar events do not occur.
      We conclude that the glacial 1,470-year climate cycles could have been triggered
      by solar forcing despite the absence of a 1,470-year solar cycle.

PMID- 16281043
TI  - Testosterone replacement therapy and the risk of prostate cancer. Is there a
      link?
AB  - Substantial evidence supports the value of testosterone replacement therapy (TRT)
      in improving quality of life in men with proven aging male syndrome (AMS).
      Benefits of TRT include improved bone mineral density, reduced fracture risk,
      increased muscle mass, and improved mood, sense of well being, and libido, among
      others. There is currently a heated debate about the theoretical association
      between TRT and the initiation, progression, and aggressiveness of prostate
      cancer; however, this link has not been uniformly studied, and any results have
      been contradictory and nonconclusive. Although no clear evidence links TRT to
      prostate cancer, the possibility of increasing the risk of a clinical
      manifestation of a latent pre-existing malignancy can influence the decision
      about TRT use. Current recommendations are to exclude prostate cancer before
      initiating TRT in men over age 40 and to closely monitor men in the first year of
      testosterone replacement, followed by observation in subsequent years.

PMID- 16281044
TI  - Penis invalidating cicatricial outcomes in an enlargement phalloplasty case with
      polyacrylamide gel (Formacryl).
AB  - The present article reports the case of a patient subjected to polyacrylamide
      polymers-composed gel cutaneous infiltration in the penis for cosmetic purposes,
      resulting in severe invalidating outcomes. A significant tissue reaction to the
      subcutaneous injection of polyacrylamide gel for the penis enlargement purpose
      resulted in permanent and invalidating scars both on the esthetic and functional
      levels. Such a result must be simply taken into account both singly and in the
      light of the international literature to exclude this method as standard uro
      andrologic activity.

PMID- 16281045
TI  - Gene transfer for the therapy of erectile dysfunction: progress in the 21st
      century.
AB  - Gene transfer represents the next potential era of advancement in medicine for
      the prevention of the effects of aging or for treatment of genetic or acquired
      disease. For gene transfer to be a practical successor to today's oral and
      minimally invasive therapies, the product must have a high safety profile and a
      long duration of effectiveness to correct the need for on-demand administration.
      Several types of vectors have been used in preclinicals studies, but because of
      widely publicized adverse events, progress using viral vectors in humans has been
      limited. There is a current phase I human trial using naked DNA as the vector
      with the maxi-K gene to modify cellular contractility. Preliminary results in the
      safety trial thus far have shown no treatment-related adverse events, no transfer
      to the semen, and the possibility of efficacy in one participant.

PMID- 16281046
TI  - Tyrosine-612 in PDE5 contributes to higher affinity for vardenafil over
      sildenafil.
AB  - Despite close structural similarity, vardenafil (Levitra) is 32-fold more potent
      than sildenafil (Viagra) to inhibit cGMP-binding cGMP-specific PDE (PDE5); this
      is due to differences between their heterocyclic rings. In co-crystals with PDE5,
      one of the rings of vardenafil or sildenafil interacts with Tyr(612), a catalytic
      site AA, via (1) a hydrogen bond with a water molecule and (2) hydrophobic bonds.
      For mutant PDE5(Y612F), which ablates hydrogen-bonding potential, vardenafil or
      sildenafil inhibition was strengthened (2.2- or 3.0-fold, respectively), implying
      that the Tyr(612) hydroxyl is a negative determinant for these inhibitors. For
      mutant PDE5(Y612A), which ablates both hydrogen bonding and hydrophobic-bonding
      potential, vardenafil inhibition was weakened much more than sildenafil
      inhibition (122- and 26-fold, respectively), suggesting that hydrophobic bonds
      involving Tyr(612) are stronger for vardenafil than for sildenafil.

PMID- 16281047
TI  - Testing for fetal exposure to illicit drugs using umbilical cord tissue vs
      meconium.
AB  - OBJECTIVE: We assessed the agreement of testing for fetal exposure to illicit
      drugs contrasting paired specimens of meconium vs umbilical cord tissue. METHODS:
      We obtained paired samples of meconium and umbilical cord tissue from 118
      pregnancies with high suspicion of illicit drug use by the mothers. Each specimen
      was tested for amphetamines, opiates, cocaine, cannabinoids, and phencyclidine
      using drug class-specific immunoassays. RESULTS: The agreement of drug screening
      results between cord and meconium was above 90% for all drugs tested. Meconium
      identified 21 cases as positive for amphetamines. The paired cord identified 20
      of these, and in addition identified three other positives that the meconium
      labeled as negative. Gas chromatography-mass spectrometry confirmed these three
      cord samples as methamphetamine positive. Meconium identified 97 samples that
      were negative for amphetamines, while the cord identified 94 of these as negative
      but three as positive. Agreement of cord with meconium for amphetamines was
      96.6%. The concordance for opiates was 94.9%, for cocaine was 99.2%, and for
      cannabinoids was 90.7%. CONCLUSIONS: Umbilical cord tissue performs as well as
      meconium in assessing fetal drug exposure to amphetamines, opiates, cocaine, and
      cannabinoids. Results of studies using the cord may have a more rapid return to
      the clinician, because waiting for meconium to be passed sometimes requires
      several days. Moreover, in some cases the meconium is passed in utero making
      collection impossible, whereas cord should always be available for drug testing.

PMID- 16281048
TI  - Fetal pulse oximetry and neonatal outcome: a study in a developing country.
AB  - BACKGROUND: The aim of this cohort, prospective study was to compare the
      diagnostic value of intrapartum fetal pulse oximetry (FPO) with that of fetal
      scalp blood gas (FSBG) for an abnormal neonatal outcome in cases with abnormal
      fetal heart rate (FHR) tracings. METHODS: Fetal oxygen saturation was
      continuously monitored with Nellcor N-400 FPO during labor. Simultaneous FSBG
      determinations were obtained. The results were analyzed in relation to umbilical
      arterial cord blood pH and neonatal outcome. Studied FPO cutoff levels were 30
      and 40% hemoglobin saturation and that of FSBG pH was 7.2. RESULTS: During the
      study, there were 9825 deliveries; 415 had abnormal FHR. Only 150 fulfilled the
      whole screening panel. When the outcome variable was umbilical arterial pH, the
      positive predictive values of the three methods (FPO30, FPO40, FSBG) were 57, 61
      and 65% and the negative predictive values were 43, 39 and 35% respectively. The
      sensitivity of FPO30 was highest (75%). Considering abnormal neonatal outcome,
      again the sensitivity was also highest for FPO30 (89%). The sensitivity of FSBG
      was 82%. The specificity of the three methods were 53, 49 and 38% respectively.
      CONCLUSION: The diagnostic value of intrapartum FPO compares favorably with FSBG.
      FPO seems to be a reliable and less invasive tool and may decrease unnecessary
      interventions and unnecessary fetal scalp blood sampling in cases of suspected
      fetal distress. The FPO cutoff of 30% saturation defined by previous studies
      appears to be appropriate.

PMID- 16281049
TI  - Monochorionic diamniotic infants without twin-to-twin transfusion syndrome.
AB  - BACKGROUND: Monochorionic-diamniotic twins (MoDi) occur in 0.3% of all
      pregnancies. Twin-to-twin transfusion syndrome (TTS) that occurs in 20% of MoDi
      pregnancies is associated with high perinatal morbidity and mortality. MoDi twins
      without TTS are more frequent (80%) but have been scarcely reported. OBJECTIVE:
      To study perinatal morbidity and mortality of 74 MoDi twin sets without TTS and
      to compare it to that of 38 sets of MoDi twins with TTS. METHODS: Chorionicity
      was determined by gender and placental examination. Gestational age (GA) was set
      by sonography and pediatric examination. TTS was diagnosed clinically and by
      sonography, discordance was defined by twins birth weight difference > or =20%,
      and fetal growth restriction was determined by using a twin-specific nomogram.
      RESULTS: MoDi twin pregnancies without and with TTS were similar in demographics,
      live births, history of preeclampsia, fetal distress and cesarean delivery. They
      were different (p<0.01) in discordant pregnancies (36 and 79%), GA at delivery
      (32 and 29 weeks) intrauterine growth restriction (39 and 89%) and neonatal
      mortality (12 and 36%). Concordant (47 sets) and discordant (27 sets) MoDi twins
      without TTS were clinically similar. CONCLUSIONS: MoDi twins without TTS have
      high rates of birth weight discordance, fetal growth restriction, fetal distress,
      prematurity and cesarean delivery. Although their perinatal mortality is low, the
      reported occurrence and the short- and long-term impacts of fetal and neonatal
      morbidities warrants attention.

PMID- 16281050
TI  - A bedside prediction-scoring model for late-onset neonatal sepsis.
AB  - OBJECTIVE: Insufficient tools for bedside prediction of late-onset neonatal
      sepsis (LNS) initiated this study. The objective was to develop and validate a
      simple prediction-scoring model for LNS defined as culture-proven sepsis
      occurring 72 hours after birth. METHODS: The study was performed at a university
      hospital in Bangkok. The derivation phase included medical records of 1870
      neonates, randomly selected from 9347 records of neonates who had been
      hospitalized for >72 hours during 1998 to 2000, of which 1824 records were
      available. In all, 100 neonates were clinically suspected of sepsis and 17 had
      proven LNS. The validation phase included 73 neonates suspected of having sepsis
      during July 2002 to June 2003 and 25 who had LNS. Weighted coefficients from
      Cox's proportional hazards model and receiver-operating-characteristic (ROC)
      curve analysis were used. RESULTS: The incidence density of LNS was 17/11355
      (1.5/1000) person-days. A scoring model was developed and consisted of the
      following: hypotension (score 4), abnormal body temperature (score 3),
      respiratory insufficiency (score 2), neutrophil band form fraction >1% (score 2),
      platelet count <150 x 10(3)/microl (score 2), and umbilical venous
      catheterization (1 to 7 or >7 days; score 2 or 4). The area under the ROC curves
      for prediction of LNS in a neonate suspected of sepsis in each of the two phases
      was 0.85 and 0.80, respectively (p=0.436). The mean probabilities of LNS were
      approximately 0.10 (low risk) for scores from 0 to 3; 0.50 (intermediate risk)
      for scores from 4 to 6; and 0.70 (high risk) for scores > or =7. CONCLUSION: A
      simple prediction-scoring model for LNS was developed. Validation of the scores
      suggested good diagnostic performance.

PMID- 16281051
TI  - Global notes: the 10/90 gap disparities in global health research.

PMID- 16281052
TI  - Metalloendoprotease cleavage triggers gelsolin amyloidogenesis.
AB  - Amyloid diseases like Alzheimer's disease and familial amyloidosis of Finnish
      type (FAF) stem from endoproteolytic cleavage of a precursor protein to generate
      amyloidogenic peptides that accumulate as amyloid deposits in a tissue-specific
      manner. FAF patients deposit both 8 and 5 kDa peptides derived from mutant
      (D187Y/N) plasma gelsolin in the extracellular matrix (ECM). The first of two
      aberrant sequential proteolytic events is executed by furin to yield a 68 kDa
      (C68) secreted fragment. We now identify the metalloprotease MT1-matrix
      metalloprotease (MMP), an integral membrane protein active in the ECM, as a
      protease that processes C68 to the amyloidogenic peptides. We further demonstrate
      that ECM components are capable of accelerating gelsolin amyloidogenesis.
      Proteolysis by MT1-MMP-like proteases proximal to the unique chemical environment
      of the ECM offers an explanation for the tissue-specific deposition observed in
      FAF and provides critical insight into new therapeutic strategies.

PMID- 16281053
TI  - A dual role for PP1 in shaping the Msn2-dependent transcriptional response to
      glucose starvation.
AB  - In yeast, glucose depletion elicits a quick response in the transcription of
      stress-related genes. The main transcriptional activator that orchestrates this
      response is Msn2, whose nuclear localization and DNA binding are negatively
      controlled by the cAMP-dependent protein kinase (PKA). Msn2 activation by sudden
      glucose depletion correlates with a fast but transient decrease in
      phosphorylation of several sites in its nuclear localization signal (NLS). Here
      we show that protein phosphatase 1 (PP1) is the direct antagonist of PKA
      dependent phosphorylation at the Msn2 nuclear import domain and therefore a
      potential mediator of glucose starvation signals that target this transcription
      factor. Apart from PKA, the protein kinase Snf1 can also directly modify one of
      the Msn2 phosphorylation sites (S582) and thereby repress Msn2 function.
      Consequently, in snf1 mutants, rephosphorylation of the NLS happens to be much
      slower during prolonged starvation. Thus, a second, Reg1-dependent form of PP1
      indirectly influences Msn2 functionality by modulating Snf1 kinase activation and
      repression. Different activities of PP1 are therefore involved in shaping
      induction and adaptation of the transcriptional stress response during acute
      glucose starvation.

PMID- 16281054
TI  - Structural insight into poly(A) binding and catalytic mechanism of human PARN.
AB  - Poly(A)-specific ribonuclease (PARN) is a processive, poly(A)-specific 3'
      exoribonuclease. The crystal structure of C-terminal truncated human PARN
      determined in two states (free and RNA-bound forms) reveals that PARNn is folded
      into two domains, an R3H domain and a nuclease domain similar to those of Pop2p
      and epsilon186. The high similarity of the active site structures of PARNn and
      epsilon186 suggests that they may have a similar catalytic mechanism. PARNn forms
      a tight homodimer, with the R3H domain of one subunit partially enclosing the
      active site of the other subunit and poly(A) bound in a deep cavity of its
      nuclease domain in a sequence-nonspecific manner. The R3H domain and, possibly,
      the cap-binding domain are involved in poly(A) binding but these domains alone do
      not appear to contribute to poly(A) specificity. Mutations disrupting
      dimerization abolish both the enzymatic and RNA-binding activities, suggesting
      that the PARN dimer is a structural and functional unit. The cap-binding domain
      may act in concert with the R3H domain to amplify the processivity of PARN.

PMID- 16281055
TI  - Inhibition of cap-dependent translation via phosphorylation of eIF4G by protein
      kinase Pak2.
AB  - Translation is downregulated in response to a variety of moderate stresses,
      including serum deprivation, hyperosmolarity and ionizing radiation. The
      cytostatic p21-activated protein kinase 2 (Pak2)/gamma-PAK is activated under the
      same stress conditions. Expression of wild-type Pak2 in cells and addition of
      Pak2 to reticulocyte lysate inhibit translation, while kinase-inactive mutants
      have no effect. Pak2 binds to and phosphorylates initiation factor (eIF)4G, which
      inhibits association of eIF4E with m(7)GTP, reducing initiation. The Pak2-binding
      site maps to the region on eIF4G that contains the eIF4E-binding site; Pak2 and
      eIF4E compete for binding to this site. Using an eIF4G-depleted reticulocyte
      lysate, reconstitution with mock-phosphorylated eIF4G fully restores translation,
      while phosphorylated eIF4G reduces translation to 37%. RNA interference releases
      Pak2-induced inhibition of translation in contact-inhibited cells by 2.7-fold.
      eIF4G mutants of the Pak2 site show that S896D inhibits translation, while S896A
      has no effect. Activation of Pak2 in response to hyperosmotic stress inhibits cap
      dependent, but not IRES-driven, initiation. Thus, a novel pathway for mammalian
      cell stress signaling is identified, wherein activation of Pak2 leads to
      inhibition of cap-dependent translation through phosphorylation of eIF4G.

PMID- 16281056
TI  - SOD2 overexpression: enhanced mitochondrial tolerance but absence of effect on
      UCP activity.
AB  - We have created P1 artificial chromosome transgenic mice expressing the human
      mitochondrial superoxide dismutase 2 (SOD2) and thus generated mice with a
      physiologically controlled augmentation of SOD2 expression leading to increased
      SOD2 enzyme activities and lowered superoxide levels. In the transgenic mice,
      effects on mitochondrial function such as enhanced oxidative capacity and greater
      resistance against inducers of mitochondrial permeability were observed.
      Superoxide in the mitochondrial matrix has been proposed to activate uncoupling
      proteins (UCPs), thus providing a feedback mechanism that will lower respiratory
      chain superoxide production by increasing a proton leak across the inner
      mitochondrial membrane. However, UCP1 and UCP3 activities and mitochondrial ATP
      production rates were not altered in isolated mitochondria from SOD2 transgenic
      mice, despite lowered superoxide levels. Globally, the transgenic mice displayed
      normal resting metabolic rates, indicating an absence of effect on any UCP
      activities, and normal oxygen consumption responses after norepinephrine
      injection. These results strongly suggest that endogenously generated matrix
      superoxide does not regulate UCP activity and in vivo energy expenditure.

PMID- 16281057
TI  - SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered
      IRF-3 activation pathways.
AB  - Viral infection or TLR3 engagement causes activation of the transcription factors
      IRF-3 and NF-kappaB, which collaborate to induce transcription of type I IFN
      genes. IKKepsilon and TBK1 are two IKK-related kinases critically involved in
      virus- and TLR3-triggered activation of IRF-3. We identified a protein termed
      SIKE (for Suppressor of IKKepsilon) that interacts with IKKepsilon and TBK1. SIKE
      is associated with TBK1 under physiological condition and dissociated from TBK1
      upon viral infection or TLR3 stimulation. Overexpression of SIKE disrupted the
      interactions of IKKepsilon or TBK1 with TRIF, RIG-I and IRF-3, components in
      virus- and TLR3-triggered IRF-3 activation pathways, but did not disrupt the
      interactions of TRIF with TRAF6 and RIP, components in TLR3-triggered NF-kappaB
      activation pathway. Consistently, overexpression of SIKE inhibited virus- and
      TLR3-triggered interferon-stimulated response elements (ISRE) but not NF-kappaB
      activation. Knockdown of SIKE potentiated virus- and TLR3-triggered ISRE but not
      NF-kappaB activation. Moreover, overexpression of SIKE inhibited IKKepsilon- and
      TBK1-mediated antiviral response. These findings suggest that SIKE is a
      physiological suppressor of IKKepsilon and TBK1 and plays an inhibitory role in
      virus- and TLR3-triggered IRF-3 but not NF-kappaB activation pathways.

PMID- 16281058
TI  - Structural basis for UTP specificity of RNA editing TUTases from Trypanosoma
      brucei.
AB  - Trypanosomatids are pathogenic protozoa that undergo a unique form of post
      transcriptional RNA editing that inserts or deletes uridine nucleotides in many
      mitochondrial pre-mRNAs. Editing is catalyzed by a large multiprotein complex,
      the editosome. A key editosome enzyme, RNA editing terminal uridylyl transferase
      2 (TUTase 2; RET2) catalyzes the uridylate addition reaction. Here, we report the
      1.8 A crystal structure of the Trypanosoma brucei RET2 apoenzyme and its
      complexes with uridine nucleotides. This structure reveals that the specificity
      of the TUTase for UTP is determined by a crucial water molecule that is
      exquisitely positioned by the conserved carboxylates D421 and E424 to sense a
      hydrogen atom on the N3 position of the uridine base. The three-domain structure
      also unveils a unique domain arrangement not seen before in the
      nucleotidyltansferase superfamily, with a large domain insertion between the
      catalytic aspartates. This insertion is present in all trypanosomatid TUTases. We
      also show that TbRET2 is essential for survival of the bloodstream form of the
      parasite and therefore is a potential target for drug therapy.

PMID- 16281061
TI  - Evaluation of cerebral blood flow by single-photon emission computed tomography
      in young Asian Indians with hypertension.
AB  - The objective of the study was to investigate abnormalities of regional cerebral
      blood flow (rCBF) in young (age 33.0+/-6.3 years; range 21-45 years) non-diabetic
      and normolipidemic Asian Indians with hypertension. The rCBF was assessed with
      single-photon emission computed tomography (SPECT) in patients with hypertension
      (n = 33) and healthy controls (n = 20). The SPECT findings were normal in 41
      subjects and showed abnormalities of cerebral perfusion in 10 subjects, all of
      which were hypertensive patients. These observations are extremely important for
      a vast number of young hypertensive patients in India. To prevent cerebrovascular
      accidents in future, patients with hypertension and decreased rCBF should be
      carefully monitored and their hypertension should be strictly controlled. These
      subjects may also be researched as potential candidates for preventive
      antiplatelet therapy.

PMID- 16281059
TI  - Structure of a central stalk subunit F of prokaryotic V-type ATPase/synthase from
      Thermus thermophilus.
AB  - The crystal structure of subunit F of vacuole-type ATPase/synthase (prokaryotic V
      ATPase) was determined to of 2.2 A resolution. The subunit reveals unexpected
      structural similarity to the response regulator proteins that include the
      Escherichia coli chemotaxis response regulator CheY. The structure was
      successfully placed into the low-resolution EM structure of the prokaryotic holo
      V-ATPase at a location indicated by the results of crosslinking experiments. The
      crystal structure, together with the single-molecule analysis using fluorescence
      resonance energy transfer, showed that the subunit F exhibits two conformations,
      a 'retracted' form in the absence and an 'extended' form in the presence of ATP.
      Our results postulated that the subunit F is a regulatory subunit in the V
      ATPase.

PMID- 16281060
TI  - The pre-B-cell receptor induces silencing of VpreB and lambda5 transcription.
AB  - The pre-B-cell receptor (pre-BCR), composed of Ig heavy and surrogate light chain
      (SLC), signals pre-BII-cell proliferative expansion. We have investigated whether
      the pre-BCR also signals downregulation of the SLC genes (VpreB and lambda5),
      thereby limiting this expansion. We demonstrate that, as BM cells progress from
      the pre-BI to large pre-BII-cell stage, there is a shift from bi- to mono-allelic
      lambda5 transcription, while the second allele is silenced in small pre-BII
      cells. A VpreB1-promoter-driven transgene shows the same pattern, therefore
      suggesting that VpreB1 is similarly regulated and thereby defines the promoter as
      a target for transcriptional silencing. Analyses of pre-BCR-deficient mice show a
      temporal delay in lambda5 downregulation, thereby demonstrating that the pre-BCR
      is essential for monoallelic silencing at the large pre-BII-cell stage. Our data
      also suggest that SLP-65 is one of the signaling components important for this
      process. Furthermore, the VpreB1/lambda5 alleles undergo dynamic changes with
      respect to nuclear positioning and heterochromatin association, thereby providing
      a possible mechanism for their transcriptional silencing.

PMID- 16281062
TI  - Effects of losartan and irbesartan on serum uric acid in hypertensive patients
      with hyperuricaemia in Chinese population.
AB  - Therapy with losartan compared to irbesartan was performed in a Chinese sample of
      hypertensive patients with elevated serum uric acid (SUA) levels. After 1 week of
      screening and a 2 week single-blinded placebo baseline period, patients were
      treated for 4 weeks with losartan 50 mg or irbesartan 150 mg. After 4 weeks,
      patients with SiDBP <90 mmHg and SiSBP <140 mmHg continued the same dose regimen
      for another 4 weeks. If blood pressure was not controlled after 4 weeks of
      treatment, the dose of either regimen was doubled to losartan 100 mg and
      irbesartan 300 mg. There were 351 patients randomized (176 to losartan and 175 to
      irbesartan), and of these, 325 patients completed the study (162 in the losartan
      group and 163 in the irbesartan group). At baseline, the median SUA level in the
      losartan group was 422 and 420 micromol/l in the irbesartan group. At 8 weeks of
      therapy, SUA decreased by 63 mumol/l in the losartan group compared to 12 mumol/l
      in the irbesartan group (P < 0.0001). Blood pressure declined comparably in both
      groups from 151/92 mmHg at baseline to 137/83 and 135/83 (losartan and
      irbesartan, respectively, NS). No severe AEs were found for either treatment
      group. Therapy with losartan decreased SUA levels significantly more than
      irbesartan in Chinese patients with hypertension and elevated SUA levels,
      demonstrating the unique uricosuric effect of this ARB in this ethnic group.

PMID- 16281063
TI  - Absolute lymphocyte count recovery after induction chemotherapy predicts superior
      survival in acute myelogenous leukemia.
AB  - Absolute lymphocyte count (ALC) recovery postautologous stem cell transplantation
      is an independent predictor for survival in acute myelogenous leukemia (AML). The
      role of ALC recovery after induction chemotherapy (IC) in AML is unknown. We
      hypothesize that ALC recovery after IC has a direct impact on survival. We have
      now evaluated the impact of ALC recovery after IC on overall survival (OS) and
      leukemia-free survival (LFS) in 103 consecutive, newly diagnosed AML patients
      treated with standard IC and consolidation chemotherapy (CC) from 1998 to 2002.
      ALC recovery was studied at days 15 (ALC-15), 21 (ALC-21), 28 (ALC-28) after IC
      and before the first CC (ALC-CC). Superior OS and LFS at each time point were
      observed with an ALC-15, ALC-21, ALC-28, and ALC-CC > or = 500 cells/microl.
      Patients with an ALC > or = 500 cells/microl at all time points vs those who did
      not have superior OS and LFS (not reached vs 13 months, P<0.0001; and not reached
      vs 11 months, P<0.0001, respectively). Multivariate analysis demonstrated ALC >
      or = 500 cells/microl at all time points to be an independent prognostic factor
      for survival. Our data suggest a critical role of lymphocyte (immune) recovery on
      survival after IC in AML.

PMID- 16281065
TI  - Reply to 'Epidemiological analysis of second primary malignancies in more than
      9500 patients treated with imatinib' by Pilot et al.

PMID- 16281064
TI  - Imatinib does not impair specific antitumor T-cell immunity in patients with
      chronic myeloid leukemia.

PMID- 16281066
TI  - A transgenic mouse model for TEL-JAK2-induced B-cell lymphoma/leukemia.

PMID- 16281067
TI  - Overcoming MDR-associated chemoresistance in HL-60 acute myeloid leukemia cells
      by targeting sphingosine kinase-1.
AB  - We examined the involvement of sphingosine kinase-1, a critical regulator of the
      sphingolipid balance, in susceptibility to antineoplastic agents of either
      sensitive or multidrug-resistant acute myeloid leukemia cells. Contrary to
      parental HL-60 cells, doxorubicin and etoposide failed to trigger apoptosis in
      chemoresistant HL-60/Doxo and HL-60NP16 cells overexpressing MRP1 and MDR1,
      respectively. Chemosensitive HL-60 cells displayed sphingosine kinase-1
      inhibition coupled with ceramide generation. In contrast, chemoresistant HL-60/
      Doxo and HL-60/VP16 had sustained sphingosine kinase-1 activity and did not
      produce ceramide during treatment. Enforced expression of sphingosine kinase-1 in
      chemosensitive HL-60 cells resulted in marked inhibition of apoptosis that was
      mediated by blockade of mitochondrial cytochrome c efflux hence suggesting a
      control of apoptosis at the pre-mitochondrial level. Incubation with cell
      permeable ceramide of chemoresistant cells led to a sphingosine kinase-1
      inhibition and apoptosis both prevented by sphingosine kinase-1 over-expression.
      Furthermore, F-12509a, a new sphingosine kinase inhibitor, led to ceramide
      accumulation, decrease in sphingosine 1-phosphate content and caused apoptosis
      equally in chemosensitive and chemoresistant cell lines that is inhibited by
      adding sphingosine 1-phosphate or overexpressing sphingosine kinase-1. F-12509a
      induced classical apoptosis hallmarks namely nuclear fragmentation, caspase-3
      cleavage as well as downregulation of antiapoptotic XIAP, and release of
      cytochrome c and SMAC/Diablo.

PMID- 16281068
TI  - Fatty acids, inhibitors for the DNA binding of c-Myc/Max dimer, suppress
      proliferation and induce apoptosis of differentiated HL-60 human leukemia cell.
AB  - c-Myc is instrumental in the progression of Burkitt's lymphoma including HL-60
      human leukemia cells. We tested fatty acids for their inhibitory effect on the
      DNA binding of c-Myc/Max dimeric proteins of human origin, prepared as
      recombinant proteins encompassing DNA binding (basic) and dimerization (HLHZip)
      domain, and found that those suppress proliferation and induce apoptosis of DMSO
      differentiated HL-60 cells. The analyzed IC50 values of myristic acid, stearic
      acid, gamma-linolenic acid, linoleic acid, linolenic acid and arachidonic acid by
      EMSA were 97(+/-3), 2.2(+/-1.2), 55(+/-5), 32(+/-2), 62(+/-12), 22(+/-2)microM
      for DNA binding of recombinant c-Myc/Max, respectively. According to the results
      shown by XTT assay, their influence on proliferation was quite different from the
      rank order of IC50. Whereas the degree of influence of the unsaturated fatty
      acids on the proliferation of DMSO-differentiated HL-60 cells was similar, the
      influence of saturated fatty acids, stearic acid in particular, was very weak at
      same concentrations. In addition, we confirmed that these fatty acids have no
      influence on the expression of c-Myc in DMSO-differentiated HL-60 cells. Our
      experiments demonstrated that the inhibitors for the DNA binding of c-Myc/Max
      contribute to the downregulation of Myc-dependent proliferation and to the
      inducement of apoptosis, and serve as an exploration of potent new inhibitors.

PMID- 16281069
TI  - Inhibition of human leukemia xenograft in nude mice by adenovirus-mediated tissue
      inhibitor of metalloproteinase-3.
AB  - Considerable studies have demonstrated the pivotal roles of matrix
      metalloproteinases (MMPs) in leukemia dissemination and extramedullary
      infiltration. Tissue inhibitors of matrix metalloproteinases (TIMPs) are
      multifunctional proteins with MMPs inhibitory effects. However, little is known
      about the application of TIMPs in the treatment of leukemia. Here, we
      investigated the effects of TIMP-3 overexpression via adenoviral gene delivery on
      the in vitro growth and invasiveness of leukemic cells and the in vivo progress
      of K562-derived xenografts in nude mice. The in vitro invasiveness of K562 cells
      was markedly impaired by AdTIMP-3 infection. Moreover, TIMP-3 significantly
      inhibited K562-derived angiogenic factors-induced proliferation, migration and
      bFGF-induced tube formation of endothelial cells (ECs) in vitro, and reduced VEGF
      induced gelatinases expression and activation in ECs. Although TIMP-3
      overexpression had no direct effect on the growth of K562 cells in vitro,
      repeated intratumoral injection of AdTIMP-3 significantly inhibited the growth of
      K562 xenografts in nude mice. Furthermore, lower microvessel density, less vessel
      maturity and increased apoptosis were observed in AdTIMP-3-treated K562
      xenografts, suggesting the importance of antiangiogenic action of TIMP-3. These
      data demonstrated the potential of applying AdTIMP-3 as an effective
      antiangiogenic adjuvant in the treatment of leukemia progression.

PMID- 16281070
TI  - The Eighth International Childhood Acute Lymphoblastic Leukemia Workshop ('Ponte
      di legno meeting') report: Vienna, Austria, April 27-28, 2005.
AB  - The International Acute Lymphoblastic Leukemia Working Group, the so-called
      'Ponte di Legno Workshop' has led to substantial progress in international
      collaboration in leukemia research. On April 27-28, 2005, the 8th Meeting was
      held in Vienna, Austria, to continue the discussions about special common
      treatment elements in randomized clinical trials, ethical and clinical aspects of
      therapy. Furthermore, collaborative projects of clinical relevance with special
      emphasis on rare genetic subtypes of Childhood ALL were established. The
      following report summarizes the achievements and aspects of possible future
      cooperation.

PMID- 16281071
TI  - Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia
      (AML) with favorable cytogenetics [t(8;21) and inv(16)].
AB  - Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a
      good prognosis with current anthracycline- and cytarabine-based protocols. Tandem
      analysis with flow cytometry (FC) and real-time RT-PCR (RQ-PCR) was applied to 55
      patients, 28 harboring a t(8;21) and 27 an inv(16), including one case with a
      novel CBFbeta/MYH11 transcript. A total of 31% (n=17) of CR patients relapsed:
      seven with t(8;21) and 10 with inv(16). The mean amount of minimal residual
      disease (MRD) detected by FC in relapsed and nonrelapsed patients was markedly
      different: 0.3 vs 0.08% (P=0.002) at the end of treatment. The mean number of
      fusion transcript copies/ ABL x 10(4) also differed between relapsed and non
      relapsed patients: 2385 vs 122 (P=0.001) after induction, 56 vs 7.6 after
      intensification (P=0.0001) and 75 vs 3.3 (P=0.0001) at the end of chemotherapy.
      Relapses were more common in patients with FC MRD level >0.1% at the end of
      treatment than in patients with < or = 0.1%: cumulative incidence of relapse
      (CIR) was 67 and 21% (P=0.03), respectively. Likewise, using RQ-PCR, a cutoff
      level of >10 copies at the end of treatment correlated with a high risk of
      relapse: CIR was 75% for patients with RQ-PCR >10 compared to 21% for patients
      with RQ-PCR levels < or = 10 (P=0.04). Combined use of FC and RQ-PCR may improve
      MRD detection, and provide useful clinical information on relapse kinetics in AML
      patients.

PMID- 16281072
TI  - Mutations of genes in the receptor tyrosine kinase (RTK)/RAS-BRAF signal
      transduction pathway in therapy-related myelodysplasia and acute myeloid
      leukemia.
AB  - Mutations of the FLT3, c-KIT, c-FMS, KRAS, NRAS, BRAF and CEBPA genes in the
      receptor tyrosine kinase (RTK)/RAS-BRAF signal-transduction pathway are frequent
      in acute myeloid leukemia (AML). We examined 140 patients with therapy-related
      myelodysplasia or AML (t-MDS/t-AML) for point mutations of these seven genes. In
      all, 11 FLT3, two c-KIT, seven KRAS, eight NRAS and three BRAF mutations were
      identified in 29 patients (21%). All but one patient with a FLT3 mutation
      presented with t-AML (P=0.0002). Furthermore, FLT3 mutations were significantly
      associated with previous radiotherapy without chemotherapy (P=0.03), and with a
      normal karyotype (P=0.004), but inversely associated with previous therapy with
      alkylating agents (P=0.003) and with -7/7q- (P=0.001). RAS mutations were
      associated with AML1 point mutations (P=0.046) and with progression from t-MDS to
      t-AML (P=0.008). Noteworthy, all three patients with BRAF mutations presented as
      t-AML of M5 subtype with t(9;11)(p22;q23) and MLL-rearrangement (P=0.01). In t
      AML RAS/BRAF mutations were significantly associated with a very short survival
      (P=0.017). Half of the patients with a mutation in the RTK/RAS-BRAF signal
      transduction pathway (denoted 'class-I' mutations) simultaneously disclosed
      mutation of a hematopoietic transcription factor (denoted 'class-II' mutations)
      (P=0.046) suggesting their cooperation in leukemogenesis.

PMID- 16281074
TI  - D276G mutation is associated with a poor prognosis in imatinib mesylate-resistant
      chronic myeloid leukemia patients.

PMID- 16281073
TI  - Transient or long-term silencing of BCR-ABL alone induces cell cycle and
      proliferation arrest, apoptosis and differentiation.
AB  - BCR-ABL fusion protein, a t(9;22) translocation product is indispensable for
      generation, maintenance and progression of chronic myeloid leukemia. RNA
      interference is an approach to silence gene at post-transcriptional level. We
      show that dsRNA targeted against the translocation region leads to more than 90%
      inhibition of BCR-ABL mRNA and protein expression levels using K562 as a model.
      Lack of BCR-ABL leads to cell cycle arrest in G1 phase as observed by decrease in
      cyclin D1 and increase in p21 and p27 cdk inhibitors mRNA. Apoptosis resistance
      imparted by BCR-ABL is lost in these cells in caspase-dependent or independent
      manner. Decrease in Bcl-XL is observed along with decrease in mitochondrial
      membrane integrity. Transient removal of BCR-ABL expression has a profound effect
      on proliferation and clonogenic capacity also confirmed by long-term silencing
      using lentiviral vectors. Interestingly, low level of BCR-ABL message leads to
      enhanced erythroid differentiation and reduced expression of megakaryocytic
      markers. Importantly, in six CML patient samples studied, silencing BCR-ABL in
      the lineage depleted enriched stem cell population leads to a decrease in colony
      forming capacity. Thus, long-term silencing of BCR-ABL might prove to be a
      promising alternative approach in CML patients especially for those who do not
      respond to any other drug treatment.

PMID- 16281076
TI  - Infrequent epigenetic dysregulation of CIP/KIP family of cyclin-dependent kinase
      inhibitors in multiple myeloma.

PMID- 16281075
TI  - Improved treatment results for childhood acute myeloid leukemia in Taiwan.
AB  - To improve treatment results for children with de novo acute myeloid leukemia
      (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A,
      for AML other than acute promyelocytic leukemia (APL), for which modified
      conventional protocols were used. From January 1, 1997, to December 31, 2002, 141
      children younger than 17 years old with de novo AML were enrolled. In total, 117
      patients with non-APL AML were treated with induction therapy of idarubicin and
      cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing
      regimens for four monthly courses, and moderate-dose therapy with idarubicin and
      Ara-C for four monthly courses. The first 19 patients with APL were treated with
      all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients
      receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy
      for 2 years. Stem cell transplantation was performed in 29 patients in first
      remission with a similar outcome as chemotherapy alone. The remission rate in the
      AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year
      event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/-
      9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year
      event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.

PMID- 16281077
TI  - Successive clinical trials for childhood acute myeloid leukemia at St Jude
      Children's Research Hospital, from 1980 to 2000.
AB  - Despite substantial progress in the management of childhood acute myeloid
      leukemia (AML), only about 50% of patients are cured by intensive chemotherapy.
      The long-term results of clinical trials may reveal principles that can guide the
      development of future therapy. From 1980 to 2000, 251 patients <15 years of age
      with newly diagnosed AML were enrolled on one of the five consecutive St Jude AML
      studies. The median age of the 128 boys and 123 girls was 6.2 years; 193 were
      white, 45 black, and 13 of other racial groups. With the exception of one
      protocol (AML-83), outcomes improved in general over the two decades. The
      estimated 5-year event-free survival (+/-s.e.) was 30.8+/-5.6% for AML-80; 11.1+/
      4.3% for AML-83; 35.9+/-7.4% for AML-87; 43.5+/-6.2% for AML-91; and 45.0+/-11.1%
      for AML-97. Resistant or relapsed AML caused the great majority of treatment
      failures. Increasing the intensity of chemotherapy (AML-87) did not improve
      outcome, partially because of toxicity, nor did prolonging postremission therapy
      by adding sequential myeloablative (AML-80) or nonmyeloablative (AML-83)
      chemotherapy cycles. We conclude that subtype-specific therapies are needed to
      replace the 'one size fits all' strategy of the past two decades.

PMID- 16281079
TI  - Assay for high glucose-mediated islet cell sensitization to apoptosis induced by
      streptozotocin and cytokines.
AB  - Pancreatic beta-cell apoptosis is known to participate in the beta-cell
      destruction process that occurs in diabetes. It has been described that high
      glucose level induces a hyperfunctional status which could provoke apoptosis.
      This phenomenon is known as glucotoxicity and has been proposed that it can play
      a role in type 1 diabetes mellitus pathogenesis. In this study we develop an
      experimental design to sensitize pancreatic islet cells by high glucose to
      streptozotocin (STZ) and proinflammatory cytokines [interleukin (IL)-1beta, tumor
      necrosis factor (TNF)-alpha and interferon (IFN)-gamma]-induced apoptosis. This
      method is appropriate for subsequent quantification of apoptotic islet cells
      stained with Tdt-mediated dUTP Nick-End Labeling (TUNEL) and protein expression
      assays by Western Blotting (WB).

PMID- 16281080
TI  - Recent neuroanatomical studies on the neurovascular bundle of the prostate and
      cavernosal nerves: clinical reflections on radical prostatectomy.
AB  - The neurovascular bundle of the prostate and cavernosal nerves have been used to
      describe the same structure ever since the publication of the first studies on
      the neuroanatomy of the lower urogenital tract of men, studies that were prompted
      by postoperative complications arising from radical prostatectomy. In urological
      surgery every effort is made to preserve or restore the neurovascular bundle of
      the prostate to avoid erectile dysfunction (ED). However, the postoperative
      potency rates are yet to be satisfactory despite all advancements in radical
      prostatectomy technique. As the technology associated with urological surgery
      develops and topographical studies on neuroanatomy are cultivated, new
      observations seriously challenge the classical teachings on the topography of the
      neurovascular bundle of the prostate and the cavernosal nerves. The present
      review revisits the classical and most recent data on the topographical anatomy
      of the neurovascular bundle of the prostate and cavernosal nerves and their
      implications on radical prostatectomy techniques.

PMID- 16281081
TI  - A case-control study of risk factors for male infertility in Nigeria.
AB  - AIM: To evaluate the association between selected potential socio-demographic and
      behavioral risk factors and infertility in Nigerian men. METHODS: There were two
      groups in this study. One group consisted of 150 men with proven male
      infertility, and the other consisted of 150 fertile men with normal semen
      parameters. Both were matched for age, place of residence and key socio
      demographic variables. They were compared for sexual history, past medical and
      surgical history, past exposures to sexually transmitted infections and
      treatment, past and current use of drugs as well as smoking and alcohol intake
      history. RESULTS: Infertile men were significantly more likely than fertile men
      to report having experienced penile discharge, painful micturition and genital
      ulcers, less likely to seek treatment for these symptoms and more likely to seek
      treatment with informal sector providers. Multivariate analysis showed that male
      infertility was significantly associated with bacteria in semen cultures, self
      reporting of previous use of traditional medications and moderate to heavy
      alcohol intake, but not with smoking and occupational types. CONCLUSION:
      INFERTILITY is associated with various proxies of sexually transmitted infections
      (STIs) and poor healthcare-seeking behavior for STIs in Nigerian men.

PMID- 16281082
TI  - Effect of piperine on the epididymis of adult male rats.
AB  - AIM: To study the effect of piperine on the epididymal antioxidant system of
      adult male rats. METHODS: Adult male rats were orally administered piperine at
      doses of 1 mg/kg, 10 mg/kg and 100 mg/kg body weight each day for 30 consecutive
      days. Twenty-four hours after the last treatment, the rats were weighed and
      killed with ether and the epididymis was dissected from the bodies. Sperm
      collected from the cauda region of the epididymis was used for the assessment of
      its count, motility and viability. Caput, corpus and cauda regions of the
      epididymis were separated and homogenized separately to obtain 10 % homogenates.
      The supernatants were used for the assays of sialic acid, superoxide dismutase,
      catalase, glutathione peroxidase, glutathione reductase, lipid peroxidation and
      hydrogen peroxide generation. RESULTS: Body weight of the piperine-treated rats
      remained unchanged. The weights of the caput, corpus and cauda regions of the
      epididymis significantly decreased at dose of 100 mg/kg. Epididymal sperm count
      and motility decreased at 10 mg/kg and 100 mg/kg, and sperm viability decreased
      significantly at 100 mg/kg. Sialic acid levels in the epididymis decreased
      significantly at 100 mg/kg while significant decrease in the cauda region alone
      was observed at 10 mg/kg. A significant decline in the activities of superoxide
      dismutase, catalase, glutathione peroxidase and glutathione reductase, along with
      an increase in hydrogen peroxide generation and lipid peroxidation were observed
      at 10 mg/kg and 100 mg/kg. CONCLUSION: Piperine caused a decrease in the activity
      of antioxidant enzymes and sialic acid levels in the epididymis and thereby
      increased reactive oxygen species levels that could damage the epididymal
      environment and sperm function.

PMID- 16281083
TI  - Erythropoietin gene transfer into rat testes by in vivo electropo-ration may
      reduce the risk of germ cell loss caused by cryptorchidism.
AB  - AIM: To investigate the effects of rat Erythropoietin (Epo) on spermatogenesis by
      transferring rat Epo gene into cryptorchid testes by means of in vivo
      electroporation. METHODS: Sprague-Dawley rats with surgically-induced unilateral
      cryptorchidism were divided into three groups: the first group was given
      intratesticular injections of pCAGGS-Epo (pCAGGS-Epo group), the second group was
      given intratesticular injections of pCAGGS (pCAGGS group), and the third group
      were given intratesticular injections of phosphate-buffered saline (PBS group).
      At the same time, square electric pulses of 30 V were applied six times with a
      time constant of 100 ms. One or two weeks after injection, each testis was
      weighed and the ratio of the total number of germ cells to that of Sertoli cells
      (G/S ratio) was calculated to evaluate the impairment of spermatogenesis. Ten
      testes taken from each of the three groups were examined at each time point.
      RESULTS: The testicular weight after the injection of pCAGGS-Epo or pCAGGS
      control plasmid was (0.85+/-0.08) g and (0.83+/-0.03) g, respectively, at week 1
      (P = 0.788) and (0.62+/-0.06) g and (0.52+/-0.02) g, respectively, at week 2 (P =
      0.047). At week 1, spermatids and sperm were more abundant in testes with pCAGGS
      Epo than those in the control testes. At week 2, spermatids and sperm were hardly
      detected in either group. The G/S ratio was 23.27 +/-6.80 vs. 18.63+/-5.30 at
      week 1 (P = 0.0078) and 7.16+/-3.06 vs. 6.05+/-1.58 at week 2 (P = 0.1471),
      respectively. CONCLUSION: The transfer of Epo to rat testes by in vivo
      electroporation may reduce the risk of the germ cell loss caused by
      cryptorchidism.

PMID- 16281084
TI  - Change of the cell cycle after flutamide treatment in prostate cancer cells and
      its molecular mechanism.
AB  - AIM: To explore the effect of androgen receptor (AR) on the expression of the
      cell cycle-related genes, such as CDKN1A and BTG1, in prostate cancer cell line
      LNCaP. METHODS: After AR antagonist flutamide treatment and confirmation of its
      effect by phase contrast microscope and flow cytometry, the differential
      expression of the cell cycle-related genes was analyzed by a cDNA microarray. The
      flutamide treated cells were set as the experimental group and the LNCaP cells as
      the control. We labeled cDNA probes of the experimental group and control group
      with Cy5 and Cy3 dyes, respectively, through reverse transcription. Then we
      hybridized the cDNA probes with cDNA microarrays, which contained 8 126 unique
      human cDNA sequences and the chip was scanned to get the fluorescent values of
      Cy5 and Cy3 on each spot. After primary analysis, reverse transcription
      polymerase chain reaction (RT-PCR) tests were carried out to confirm the results
      of the chips. RESULTS: After AR antagonist flutamide treatment, three hundred and
      twenty-six genes (3.93%) expressed differentially, 97 down-regulated and 219 up
      regulated. Among them, eight up-regulated genes might be cell cycle-related,
      namely CDC10, NRAS, BTG1, Wee1, CLK3, DKFZP564A122, CDKN1A and BTG2. The CDKN1A
      and BTG1 gene mRNA expression was confirmed to be higher in the experimental
      group by RT-PCR, while p53 mRNA expression had no significant changes.
      CONCLUSION: Flutamide treatment might up-regulate CDKN1A and BTG1 expression in
      prostate cancer cells. The protein expressions of CDKN1A and BTG1 play an
      important role in inhibiting the proliferation of cancer cells. CDKN1A has a
      great impact on the cell cycle of prostate cancer cells and may play a role in
      the cancer cells in a p53-independent pathway. The prostate cancer cells might
      affect the cell cycle-related genes by activating AR and thus break the cell
      cycle control.

PMID- 16281085
TI  - Effects of icariin on erectile function and expression of nitric oxide synthase
      isoforms in castrated rats.
AB  - AIM: To investigate the effect of icariin on erectile function and the expression
      of nitric oxide synthase (NOS) isoforms in castrated rats. METHODS: Thirty-two
      adult male Wistar rats were randomly divided into one sham-operated group (A) and
      three castrated groups (B, C and D). One week after surgery, rats were treated
      with normal saline (groups A and B) or oral icariin (1 mg/[kg.day] for group C
      and 5 mg/[kg.day] for group D) for 4 weeks. One week after treatment, the
      erectile function of the rats was assessed by measuring intracavernosal pressure
      (ICP) during electrostimulation of the cavernosal nerve. The serum testosterone
      (ST) levels, the percent of smooth muscle (PSM) in trabecular tissue, and the
      expression of mRNA and proteins of neuronal nitric oxide synthase (nNOS),
      inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS)
      and phosphodiesterase V (PDE5) in corpus cavernosum (CC) were also evaluated.
      RESULTS: ICP, PSM, ST and the expression of nNOS, iNOS, eNOS and PDE5 were
      significantly decreased in group B compared with those in group A (P 0.01).
      However, ICP, PSM and the expression of nNOS and iNOS were increased in groups C
      and D compared with those in group B (P 0.05). Changes in ST and the expression
      of eNOS and PDE5 were not significant (P 0.05) in groups C and D compared with
      those in group B. CONCLUSION: Oral treatment with icariin ( 98.6 % purity) for 4
      weeks potentially improves erectile function. This effect is correlated with an
      increase in PSM and the expression of certain NOS in the CC of castrated rats.
      These results suggest that icariin may have a therapeutic effect on erectile
      dysfunction.

PMID- 16281086
TI  - Contragestazol (DL111-IT) inhibits proliferation of human androgen-independent
      prostate cancer cell line PC3 in vitro and in vivo.
AB  - AIM: To evaluate the antiproliferative activity of contragestazol (DL111-IT) on
      the human prostate cancer cell line PC3 in vitro and in vivo and to elucidate its
      potential molecular mechanisms. METHODS: The cell killing ability of DL111-IT was
      measured by the 3-(4,5-dimethylthia-zol,2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) reagent assay method and the tumor xenograft model. The cell cycle was
      analyzed by flow cytometry and protein expression, including retinoblastoma
      (pRb), cyclin-dependent kinase 4 (CDK4) and cyclin D1, was detected by Western
      blotting. RESULTS: DL111-IT exhibited high efficiency on cell growth inhibition
      of the human androgen-independent prostate cancer cell line PC3. The drug
      concentration that yielded 50% cell inhibition (IC50 value) was 9.9 mg/mL. In the
      PC3 tumor xenograft study, DL111-IT (1.25 mg/kg-20.0 mg/kg) given once a day for
      10 days significantly inhibited tumor growth, with the inhibition rate ranging
      from 21% to 50%. Flow cytometric analysis indicated that DL111-IT could cause G1
      arrest in the PC3 cell line, but not apoptosis. DL111-IT enhanced pRb expression
      and down-regulated CDK4 and cyclin D1 expression, suggesting that cell cycle
      regulation might contribute to the anticancer property of DL111-IT. CONCLUSION:
      DL111-IT inhibits the proliferation of human androgen-independent prostate cancer
      cell line PC3 in vitro and in vivo by a cell cycle regulation pathway.

PMID- 16281087
TI  - Characteristics of sildenafil erections in healthy young men.
AB  - AIM: To determine the effect of sildenafil citrate on the nocturnal penile
      erections (i.e. time to onset, the duration of erection, and the interval between
      first and second erections) of healthy young men. METHODS: Twenty-two potent men,
      23-29 years old, were recruited for the study. All subjects completed three
      sessions over consecutive nights using the RigiScan monitoring device (Dacomed,
      Minneapolis, USA). After a first night of adaptation, night 2 records were their
      baseline values, and on night 3 they received 100 mg of sildenafil citrate.
      Statistical comparisons were done between the second and third night data.
      RESULTS: The mean time to onset of the first erection with sildenafil citrate was
      (34+/-18) min, whereas it was (74+/-24) min (P 0.0001) without sildenafil
      citrate. The number of erections observed during the first 5 h after sildenafil
      citrate medication was 3.6+/-0.5 in contrast to 2.4+/-0.5 with no medication
      (P=0.001). The interval between first and second erections was shorter with
      sildenafil citrate: (52+/-26) min vs. (85+/-34) min (P = 0.01). The duration of
      the last erection was statistically significantly longer with the sildenafil
      citrate: (64 +/-33) min vs. (42 +/-28) min (P 0.001). CONCLUSION: Healthy young
      men achieved erection within 34 min after sildenafil citrate administration,
      which is shorter than the 1 h interval proposed by the manufacturer. The interval
      between the first and second erections was shorter and the duration of the last
      nocturnal erection was longer.

PMID- 16281088
TI  - Aphrodisiac potentials of the aqueous extract of Fadogia agrestis (Schweinf. Ex
      Hiern) stem in male albino rats.
AB  - AIM: To evaluate the phytochemical constituents and the aphrodisiac potential of
      the aqueous extract of Fadogia agrestis (Rubiaceae) stem in male albino rats.
      METHODS: The aqueous stem extract of the plant was screened for phytochemical
      constituents. Male rats were orally dosed with 18 mg/kg, 50 mg/kg and 100 mg/kg
      body weight, respectively, of the extract at 24 h intervals and their sexual
      behavior parameters and serum testosterone concentration were evaluated at days
      1, 3 and 5. RESULTS: Phytochemical screening revealed the presence of alkaloids
      and saponins while anthraquinones and flavonoids are weakly present. All the
      doses resulted in significant increase in mount frequency, intromission frequency
      and significantly prolonged the ejaculatory latency (P 0.05) and reduced mount
      and intromission latency (P 0.05). There was also a significant increase in serum
      testosterone concentrations in all the groups in a manner suggestive of dose
      dependence (P 0.05). CONCLUSION: The aqueous extract of Fadogia agrestis stem
      increased the blood testosterone concentrations and this may be the mechanism
      responsible for its aphrodisiac effects and various masculine behaviors. It may
      be used to modify impaired sexual functions in animals, especially those arising
      from hypotestosteronemia.

PMID- 16281089
TI  - Antispermatogenic activity of Morinda lucida extract in male rats.
AB  - AIM: To investigate the effect of Morinda lucida Benth (Rubiaceae) on the
      reproductive activity of male albino rats. METHODS: Two groups of rats were
      treated with 400 mg/(kg .d) of Morinda lucida leaf extract for 4 and 13 weeks,
      respectively. The control rats received the vehicle. All the treated rats had
      corresponding recovery groups. At the end of each experimental period, animals
      were killed and organ weights, sperm characteristics, serum testosterone levels,
      histology of the testes and fertility were assessed. RESULTS: Morinda lucida leaf
      extract did not cause any changes in body and somatic organ weights, but
      significantly increased the testis weight (P 0.05). The sperm motility and
      viability, and the epididymal sperm counts of rats treated for 13 weeks were
      significantly reduced (P 0.05). Sperm morphological abnormalities and serum
      testosterone levels were significantly increased (P 0.05). There were various
      degrees of damage to the seminiferous tubules. The extract reduced the fertility
      of the treated rats by reducing the litter size. Reversal of these changes,
      however, occurred after a period of time. CONCLUSION: The extract of Morinda
      lucida has reversible antispermatogenic properties.

PMID- 16281090
TI  - Effects of Basella alba and Hibiscus macranthus extracts on testosterone
      production of adult rat and bull Leydig cells.
AB  - AIM: To determine the androgenic effects of Basella alba and Hibiscus macranthus
      extracts in the rat and the bull, and to develop a novel in vitro test system
      using Leydig cells from bull testes. METHODS: The effect of methanol extracts
      from both plants on testosterone production in isolated Leydig cells from the rat
      and the bull was analyzed using 125I-radioimmunoassay (125I-RIA). Rat Leydig
      cells were obtained by common methods, whereas a novel technique was used to
      purify Leydig cells from bull testes. RESULTS: Bull testes from the slaughter
      house were a cheap source of pure Leydig cells. In culture, these cells produced
      testosterone for 5-6 days, which can be stimulated by human chorionic
      gonadotrophin (hCG). Basella alba extracts significantly enhanced testosterone
      production in bull and rat Leydig cells in a concentration-dependent manner.
      Hibiscus macranthus showed no androgenic effect but was shown to inhibit
      testosterone production at higher concentrations. CONCLUSION: Leydig cells
      purified from bull testes can be used as an alternative tool in experimental
      animal research. Certain fractions of Basella alba extract demonstrated
      androgenic potential whereas Hibiscus macranthus extracts did not.

PMID- 16281091
TI  - Significant reduction of sperm disomy in six men: effect of traditional Chinese
      medicine?
AB  - AIM: To test the hypothesis that levels of sperm disomy fell significantly in six
      men treated by traditional Chinese medicine (TCM). METHODS: Fluorescence in situ
      hybridization (FISH) was done on the sperm heads of six men before and during
      treatment by TCM. RESULTS: There was a significant reduction in sperm disomy in
      all six men. This coincided with TCM treatment. CONCLUSION: This is the first
      study reporting a significant reduction in sperm disomy in men over a given time
      course. The fact that this coincided with TCM treatment is intriguing but no
      conclusions can be drawn from this until placebo-controlled clinical trials are
      implemented.

PMID- 16281092
TI  - Chronic prostatitis in Korea: a nationwide postal survey of practicing urologists
      in 2004.
AB  - AIM: To examine the diagnosis and treatment of chronic prostatitis by means of a
      nationwide postal survey of practicing urologists in 2004. METHODS: A random
      sample of 850 Korean urologists from the Korean Urological Association Registry
      of Physicians were asked to complete a questionnaire that explored practicing
      characteristics, attitudes and diagnostic and treatment strategies in the
      management of chronic prostatitis. RESULTS: Of the 850 questionnaires sent, 302
      were returned (response rate 35.5%) and 275 were induced in the final analysis.
      More than 50% believed in a multifactorial etiology for chronic prostatitis and
      52% considered chronic abacterial prostatitis to be bacterial in nature. For
      routine diagnostic assessment, the most commonly used tests were reported to be
      urinalysis (95.3%), analysis of expressed prostatic secretions (89.5%) and
      digital rectal examination (81.1%). Only a few urologists use specific lower
      urinary tract cultures. Symptom assessment according to the National Institute of
      Health-Chronic Prostatitis Symptom Index was less frequently used (12.7%). First
      choices for therapy included antibiotics (96.4%), alpha-blockers (71.6%) and sitz
      baths (70.5%). If unsuccessful, urologists frequently continued to prescribe a
      second course of either alpha-blockers (69.5%) or antibiotics (57.8%).
      CONCLUSION: These data provide a picture of current practice regarding the
      management of chronic prostatitis in Korea. The diagnostic and treatment
      practices for prostatitis do not follow standard textbook algorithms. Further
      studies are needed to elucidate the etiology and pathogenesis of chronic
      prostatitis and to establish guidelines for its diagnosis and treatment.

PMID- 16281093
TI  - Evaluation of the mechanisms of damage to flexible ureteroscopes and suggestions
      for ureteroscope preservation.
AB  - AIM: To investigate the causes and costs of flexible ureteroscope damage, and to
      develop recommendations to limit damage. METHODS: The authors analysed repair
      figures and possible causes of damage to 35 instruments sent for repair to a
      leading UK supplier over a 1-year period, and calculated cost figures for
      maintenance of the instruments as opposed to repair and replacement costs.
      RESULTS: All damages were handling-induced and therefore did not fall under the
      manufacturer's warranty: 28 % were damaged by misfiring of the laser inside the
      instrument; 72 %, mainly crushing and stripping of the ureteroscope shaft tube,
      were likely to have occurred during out-of-surgery handling, washing and
      disinfection. Seventeen (4 %) instruments were not repaired and consequently
      taken out of service due to the extensive costs involved. Eighteen (51 %)
      ureteroscopes were repaired at an average cost of 10 833 USD. CONCLUSION: Damages
      to flexible ureteroscopes bear considerable costs. Most damages occur during
      handling between surgical procedures. Thorough adherence to handling procedures,
      and courses for theater staff and surgeons on handling flexible instruments may
      help to reduce these damages and prove a cost-saving investment. The authors
      provide a list of recommended procedural measures that may help to prevent such
      damages.

PMID- 16281094
TI  - Outpatient varicocelectomy performed under local anesthesia.
AB  - AIM: To report a series of varicocelectomy performed under pure local anesthesia.
      METHODS: From July 1988 to June 2003, a total of 575 patients, aged between 15
      and 73 years, underwent high ligation of the internal spermatic vein for
      treatment of a varicocele testis under a regional block in which a precise
      injection of 0.8 % lidocaine solution was delivered to involved tissues after
      exact anatomical references were made. A 100-mm visual analog scale (VAS) was
      used to assess whether the pain level was acceptable. RESULTS: The surgeries were
      bilateral in 52 cases, and unilateral in 523 cases. All were successfully
      performed on an outpatient basis except in the case of two patients, who were
      hospitalized because their surgeries required general anesthesia. Overall, 98.6 %
      (567/575) of men could go back to work by the end of the first post-operative
      week and only 8 (1.4 %) men reported feeling physical discomfort on the eighth
      day. The VAS scores varied from 11 mm to 41 mm with an average of (18.5+/-11.3)
      mm that was regarded as tolerable. CONCLUSION: This study has shown
      varicocelectomy under local anesthesia to be possible, simple, effective,
      reliable and reproducible, and a safe method with minimal complications. It
      offers the advantages of more privacy, lower morbidity, with no notable adverse
      effects resulting from anesthesia, and a more rapid return to regular physical
      activity with minor complications.

PMID- 16281095
TI  - A rare diagnosis: testicular dysgenesis with carcinoma in situ detected in a
      patient with ultrasonic microlithiasis.
AB  - A rare case is presented where a dysgenetic testis with microinvasive carcinoma
      in situ (CIS, also known as intratubular germ cell neoplasm of unclassified type
      [IGCNU] and testicular intraepithelial neoplasia [TIN]) with microinvasion to
      rete testis and the interstitial tissue was found in a 32-year-old man presenting
      with mild scrotal pain and ultrasonic testicular microlithiasis. Knowledge of the
      association of ultrasound and CIS is important to diagnose patients at the stage
      prior to development of an overt germ cell tumor. The patient had three of four
      disorders considered symptoms of the testicular dysgenesis syndrome (TDS): a
      dysgenetic left testicle with CIS, a mild left-sided cryptorchidism (high
      positioned scrotal hypotrophic testis) and a slightly reduced semen quality.
      Therefore, it should be kept in mind that a patient with one TDS symptom may
      harbour the other, even CIS or testicular cancer. Accordingly, patients with one
      TDS symptom ought to be examined for the presence of the others, and if more that
      one is present, extra concern is warranted.

PMID- 16281096
TI  - Congenital agenesis of seminal vesicle.
AB  - Congenital agenesis of the seminal vesicle (CASV) is frequently associated with
      congenital absence of the vas deferens (CAVD) or ipsilateral congenital
      vasoureteral communication. We reported two cases of a rare condition that the
      vas deferens open ectopically into Mullerian duct cyst associated with agenesis
      of the ipsilateral seminal vesicle. The diagnosis was confirmed by vasography.
      Transurethral unroofing of the Mullerian duct cyst was performed in both patients
      with favourable results, however, assisted reproductive technology (ART) was
      still necessary for them to father children.

PMID- 16281109
TI  - Patent guide for miniaturists.
AB  - Inventors who are mystified by the concepts of "nonobviousness" and "enablement"
      may be surprised to find that the two concepts have a simple explanation in
      information theory. Viewing an invention as a low-probability, high-information
      event helps explain why an invention that appears inventive (nonobvious) to an
      inventor may appear obvious to a patent examiner, and suggests some strategies
      for overcoming the examiner's bias. Viewing enablement as a means of increasing
      the probability that a claimed invention can be practiced successfully helps in
      understanding how to support a broad claim effectively by virtual or "paper"
      patenting. The notion of entropy, or mean information content, as applied to
      inventions, may guide inventors in their search for new inventions.

PMID- 16281097
TI  - Life-threatening meningitis resulting from transrectal prostate biopsy.
AB  - After antibiotic prophylaxis with metronidazole and levofloxacin, a transrectal
      sextant biopsy was performed under the guide of transrectal ultrasonography
      (TRUS) for a 75-year-old suspicious patient with prostate adenocarcinoma.
      Although antibiotics were also given after this procedure, the patient still
      developed fever, anxious, agrypnia and headache. Blood cultures remained
      negative. Lumbar puncture was performed and was consistent with Escherichia coli
      bacterial meningitis.

PMID- 16281110
TI  - DNA analysis in microfabricated formats.
AB  - The use of microfabricated DNA analysis tools utilizing microfluidics will
      provide the next generation of inexpensive DNA diagnostics. It will also provide
      methodologies to measure gene expression in a massively parallel manner,
      eventually providing the methodologies to measure most or all the human genes of
      significance on a single chip. These technologies, including PCR analysis,
      electrophoresis and gene chips are described using examples from the archival
      literature.

PMID- 16281111
TI  - Filtration of sub-100 nm particles using a bulk-micromachined, direct-bonded
      silicon filter.
AB  - For successful size separation in biomedical applications, the filter used must
      meet several strict criteria. Not only must it have precisely-machined sub-100 nm
      pores (<5% variation), but it must also be able to handle large and small volumes
      with very high reduction ratios (>10(4)). In this paper, we will present a bulk
      micromachined, direct-bonded silicon nanofilter that can remove particles as
      small as 44 nm. In doing so, we will describe the fabrication, the gas and liquid
      characterization, and the filtrations studies done on 44 nm and 100 nm beads.

PMID- 16281112
TI  - An integrated micromachined electrochemical pump and dosing system.
AB  - In this paper a micromachined electrochemically driven pump capable of dosing
      precise nanoliter amounts of liquid is presented. The pump consists of a
      micromachined channel structure realized in silicon by reactive ion etching. On
      top of this structure a Pyrex((R)) cover piece with noble metal electrodes was
      bonded. The fluid to be dispensed is stored in a meander shaped reservoir which
      is part of the channel structure. This meander starts in an electrolyte solution
      containing reservoir, on top of which two noble metal electrodes are positioned.
      By the electrochemical production of gas bubbles by electrolysis of water at
      these electrodes, liquid can be driven out of the meander. The measured volume
      displacements were in close agreement with theory. Pump rates as low as a few
      nl/s could accurately be controlled via the actuation current through the
      electrodes. By applying current pulses rather than a continuous current, preset
      amounts of fluid in the nanoliter range could be dosed successfully. Because the
      resulting device consists of simple channel structures and metal electrodes it
      can easily be integrated in miniaturized chemical analysis systems to dose
      reagents or calibration solutions.

PMID- 16281113
TI  - Microfabricated biocapsules provide short-term immunoisolation of insulinoma
      xenografts.
AB  - This study examines the viability and functionality of two insulinoma cell lines,
      RIN (1048) and betaTC6F7, encapsulated within microfabricated biocapsules.
      Surface and bulk micromachining are integrated in the biocapsule fabrication
      process, resulting in a diffusion membrane with uniform pore size distribution as
      well as mechanical and chemical stability, surrounded by an anisotropically
      etched silicon wafer, which serves as the encapsulation cavity. Insulinoma cells
      (4500 cells/biocapsule) were enclosed within these microfabricated biocapsules
      and subjected to a static incubation study after either implantation in BALB-C
      mice or incubation in vitro. Examination of retrieved microfabricated biocapsules
      revealed an insulin stimulatory index of approximately 1.5 for encapsulated RIN
      cells and 3.6 for encapsulated betaTC6F7 cells for biocapsules with 18 nm pore
      sized microfabricated membranes, similar to indices of biocapsules incubated in
      vitro. There was an 80% decrease in cell stimulatory response between in vitro
      and in vivo 66 nm-biocapsules as compared to 20% for 18 nm-biocapsules,
      indicating that the immunoisolatory effectiveness depends greatly on achieving
      uniform pore sizes in the size range of 18 nm or smaller. The present study
      demonstrates the feasibility of using microfabricated biocapsules for the
      immunoisolation of insulinoma cells lines. The microfabricated biocapsule may
      serve as an alternative to conventional polymeric based biocapsules for possible
      use as in vivo insulin secreting bioreactor.

PMID- 16281114
TI  - Array biosensor: optical and fluidics systems.
AB  - Optical and fluidics systems have been developed as central components for an
      automated array biosensor. Disposable planar waveguides are patterned with
      immobilized capture antibodies using a physically isolated patterning (PIP)
      method. The PIP method enables simultaneous deposition of several antibodies and
      completely circumvents cross-immobilization problems encountered with other array
      deposition processes. A multi-channel fluidics cell allows numerous assays to be
      performed on the patterned waveguide. The sensing arrays are optically
      interrogated using a diode laser with a tailored output to optimize coupling to
      and maximize excitation uniformity within the waveguide. A patterned cladding is
      employed to optically isolate the waveguide from perturbations induced by the
      permanently attached flow cells. Compact optics image the evanescently excited
      fluorescence onto a large area, cooled CCD array. The image data is processed and
      automated signal analysis corrects for local background and noise variations.

PMID- 16281115
TI  - Multifunctional biocompatible membrane and its application to fabricate a
      miniaturized glucose sensor with potential for use in vivo.
AB  - A multifunctional membrane with biocompatibility, diffusion-limiting effect, and
      the ability to curtail the responses of an H(2)O(2) electrode to ascorbate and
      urate was prepared. It was composed of MB, AB, and CTA, where MB is the copolymer
      of 2-methacryloyloxyethyl phosphorylcholine (MPC) and n-butylmethacrylate (BMA),
      AB is the copolymer of acrylamide-2-methylpropane sulfonic acid (AMPS) and BMA,
      CTA is cellulose triacetate. Investigation of the biocompatibility of this
      membrane showed that, compared with CTA, relatively few platelets bound to it.
      The membrane was coated onto the working electrode of a needle-type glucose
      sensor on which immobilized glucose oxidase membrane has been coated. The sensor
      did not respond to ascorbate and urate at their concentration normally
      encountered in blood. Its response was not inhibited by metal ions in blood at
      usual concentration. The sensor exhibited superior thermostability in addition to
      a rapid response (<90 seconds in batch operation), good reproducibility (RE<5%),
      good stability (more than 36 hours continuously in heparinized whole blood), and
      a wide dynamic range (5-650 mg/dl glucose). The sensor was used to determine
      glucose in serum. The data obtained from the sensor showed good agreement with
      that from a clinical autoanalyzer (R=0.973).

PMID- 16281134
TI  - Capsule endoscopy.

PMID- 16281135
TI  - Endoscopic tumor diagnosis and treatment.

PMID- 16281136
TI  - Endoscopic ultrasound.

PMID- 16281137
TI  - ERCP topics.

PMID- 16281139
TI  - Gastrointestinal bleeding.

PMID- 16281138
TI  - Colon tumours and colonoscopy.

PMID- 16281140
TI  - Barrett's esophagus.

PMID- 16281142
TI  - The Munich Polypectomy Study (MUPS): prospective analysis of complications and
      risk factors in 4000 colonic snare polypectomies.
AB  - BACKGROUND AND STUDY AIMS: Screening colonoscopy with polypectomy has been shown
      to reduce the morbidity and mortality associated with colorectal cancer. However,
      there is a lack of large and systematic prospective studies of the complications
      of polypectomy. PATIENTS AND METHODS: Data on all snare polypectomies performed
      in 13 institutions (six hospitals and seven gastroenterology offices) were
      recorded prospectively during a 20-month period, including data on a 30-day
      follow-up period. The primary end points of the study were polypectomy
      complications, which were classed as "major" or "minor". Risk factors for
      complications were analyzed for both patient characteristics and polyp
      parameters. RESULTS: A total of 3976 snare polypectomies in 2257 patients (mean
      age 64.5 years) were included in the study. The mean polyp size was 1.1 cm, and
      72% were sessile. Complications occurred in 9.7% of patients (6.1% of polyps);
      75% of these complications were minor; and the mortality rate was zero.
      Multivariate regression analysis revealed polyp size as the main risk factor,
      both for complications overall (odds ratio 6.56, 95%CI 4.45-9.67) and for major
      complications (odds ratio 31.01, 95%CI 7.53-128.1). Right-sided polyp location
      was a significant risk factor for major complications (odds ratio 2.40, 95%CI
      1.34-4.28). Setting a cut-off value of 3% as an acceptable rate for major
      complications, polyps larger than 1 cm in the right colon or 2 cm in the left
      colon, and multiple polyps carried an increased risk. CONCLUSIONS: Colonoscopic
      polypectomy is associated with a 10% rate of complications, but three-quarters of
      these are of minor clinical significance. More than 90% of the complications can
      be managed conservatively if adequate endoscopic expertise is available.
      Guidelines for intensified follow-up after polypectomy should be based on the
      size, location, and number of a patient's polyps.

PMID- 16281143
TI  - Evaluation of a novel colonoscope designed for easier passage through flexures: a
      randomized study.
AB  - BACKGROUND AND STUDY AIMS: A new colonoscope (XCF-Q160AW prototype, Olympus,
      Tokyo, Japan) has been developed, designed with an additional passive bending
      function to ease intubation through the left colonic flexure. In this study we
      investigated whether this function could be included in a standard colonoscope
      without jeopardizing general performance, particularly passage through the
      sigmoid colon. PATIENTS AND METHODS: 280 outpatients referred for routine
      colonoscopy at Telemark Hospital were randomly allocated to colonoscopy with a
      standard colonoscope (Olympus 140 series) or the XCF-Q160AW prototype. Sedation
      was given on demand. End points were cecal intubation and the patients' grading
      of pain in a questionnaire. RESULTS: Cecal intubation rates were 85% and 87% for
      standard and prototype endoscopes, respectively (P = 0.57). On-demand sedation
      was given to nine (7%) and 15 (11%) of the patients, respectively (P = 0.17). Of
      the patients, 256 (85%) returned their questionnaire, with 87 (63%) in the
      standard group and 109 (77%) in the prototype group reporting that they had
      experienced 'no pain/slight pain' (P < 0.001). In a multiple logistic regression
      analysis, this difference in experienced pain remained statistically significant
      after adjustment for interendoscopist variation and the use of the endoscope
      stiffening function. Two patients in the study, in whom there had previously been
      several unsuccessful attempts at negotiating the splenic flexure, were
      successfully examined with the prototype colonoscope. CONCLUSION: Examination
      with the Olympus XCF-Q160AW prototype with a passive bending function caused less
      pain than use of a standard Olympus 140 series colonoscope, without compromising
      other endoscope functions for colonic intubation.

PMID- 16281141
TI  - Widespread endoscopic mucosal resection of the esophagus with strategies for
      stricture prevention: a preclinical study.
AB  - BACKGROUND AND STUDY AIMS: Circumferential endoscopic mucosal resection of the
      esophagus is complicated by stricture formation. Prophylactic measures for
      avoiding such strictures have not been well studied. The aim of this preclinical
      study was to assess strategies for prevention of esophageal strictures in a
      porcine model following widespread endoscopic mucosal resection (EMR). METHODS: A
      total of 18 60-kg pigs were included in the study. The roles of strip width
      (group 1), prophylactic steroids (group 2), and prophylactic stents (group 3) in
      the prevention of post-mucosectomy strictures were studied. Six animals were
      included in each group. Esophageal mucosal resection was achieved using a novel
      widespread EMR technique previously described by our group. Animals in group 1
      underwent partial (50% circumference) mucosal resection without prophylactic
      measures, while animals in the other two groups underwent circumferential mucosal
      resection. Animals in group 2 received 80 mg of triamcinolone injected directly
      into the exposed submucosal tissue (20 mg injection in four quadrants). Animals
      in group 3 received esophageal metal stents coated with small-intestine submucosa
      (SIS) that were deployed immediately post-resection. Animals were kept alive for
      1 month. RESULTS: Partial and circumferential widespread EMRs were achieved in
      all animals. There were no procedural complications. Repeat endoscopy at 1 month
      showed no strictures in group 1. Only four animals were studied in group 2, owing
      to the high complication rate (periesophageal abscess in all animals) with one
      early death. Three of the surviving animals developed mild to tight strictures.
      In group 3, all animals developed tight strictures; however, there was early
      stent migration in four animals and premature stent removal in two animals
      because of persistent vomiting. CONCLUSIONS: Partial widespread EMR of the
      esophagus heals without stricture formation and does not require prophylactic
      intervention. The use of deep mural steroid injection following a circumferential
      resection does not appear to prevent strictures and may result in serious adverse
      events. Short-term use of esophageal stents is inadequate for stricture
      prevention. However, better results may be anticipated with longer term (at least
      6 weeks) stent use.

PMID- 16281144
TI  - Gastrointestinal findings in patients with autoimmune pancreatitis.
AB  - BACKGROUND AND STUDY AIMS: Autoimmune pancreatitis (AIP) is a condition that has
      been proposed as a clinical entity only fairly recently. Its pathogenesis
      involves autoimmune mechanisms. Although the radiological findings in patients
      with AIP have been well evaluated, few studies have focused on the
      gastrointestinal findings in these patients. The aim of this study was to explore
      the endoscopic and histological findings in the gastrointestinal tract in
      patients with autoimmune pancreatitis. PATIENTS AND METHODS: The endoscopic
      findings in the stomach (n = 10), the duodenum (n = 18), the major duodenal
      papilla (n = 18), and the colon (n = 5) in 24 patients with AIP were reviewed.
      These were compared with the results of histological examination of gastric
      mucosa (n = 13), duodenal mucosa (n = 9), the major duodenal papilla (n = 3), and
      colonic mucosa (n = 3) in these patients. All these specimens were subjected to
      immunohistochemical study using anti-IgG4 antibody. RESULTS: Foci of slightly
      pale, thickened mucosa with loss of visible vascular pattern were observed in the
      stomach in four patients and in the colon in two patients on endoscopy. Slight or
      moderate swelling of the major duodenal papilla was detected in five patients.
      Slight to moderate lymphoplasmacytic infiltration was observed in the lamina
      propria of the gastric and colonic mucosa, and of the major duodenal papilla.
      Heavy infiltration with IgG4-positive plasma cells (>10 cells per high-power
      field) was observed in the lamina propria of the stomach in seven patients, of
      the colon in two patients, and of the major duodenal papilla in three patients;
      this was not observed in the control patients, who had other diseases.
      CONCLUSIONS: Although there were no specific endoscopic findings in the stomach
      or colon in patients with autoimmune pancreatitis, foci of slightly pale,
      thickened mucosa with loss of visible vascular pattern were observed in some
      cases. This indistinct change seen on endoscopy appears to be due to heavy
      infiltration with IgG4-positive plasma cells, associated with CD4- or CD8
      positive T lymphocytes, in the lamina propria of the gastric or colonic mucosa.

PMID- 16281146
TI  - Information required to provide informed consent for endoscopy: an observational
      study of patients' expectations.
AB  - BACKGROUND AND STUDY AIMS: The aim of this study was to determine how much
      information patients require about the risk of complications in order to provide
      informed consent to undergo endoscopy. PATIENTS AND METHODS: Endoscopic
      complications and their consequences were discussed with consecutive patients who
      had undergone endoscopy. The patients were asked how common each complication
      would have to be for them to require information about the complication before
      providing adequately informed consent. RESULTS: Data were obtained from 150
      gastroscopy patients (51% male, median age 55.5 years) and 150 colonoscopy
      patients (60% male, median age 54.4 years). Patients in both groups were more
      likely to want to know about major rather than minor complications at a lower
      level of risk (P < 0.001 at a risk greater than one in 1000). Similar proportions
      of gastroscopy patients (n = 29, 19%) and colonoscopy patients (n = 21, 14 %)
      wanted to know about all possible complications, no matter how inconsequential or
      rare. Colonoscopy patients were less likely to want no information about any
      complications than gastroscopy patients (n = 1, 0.7% and n = 15, 10%,
      respectively; P < 0.001). CONCLUSIONS: The information patients require in order
      to provide informed consent is very variable. Many appear to make a judgement
      about the need for information depending on the perceived severity of the
      complication, but some want information about all complications, irrespective of
      risk and severity. The level of risk at which they require this information is
      likely to be higher than the level used by doctors who are obtaining consent from
      patients. The process may be improved by providing procedure-specific information
      leaflets that offer information regarding common and serious complications.

PMID- 16281145
TI  - Barrett's esophagus: a discrepancy between macroscopic and histological
      diagnosis.
AB  - BACKGROUND AND STUDY AIMS: The diagnosis of Barrett's esophagus at present
      requires endoscopic and histological confirmation of specialized intestinal
      metaplasia. This study prospectively analyzed the endoscopic and histological
      prevalence of Barrett's esophagus and the risk factors for the presence of
      Barrett's esophagus among patients being treated in an endoscopy unit. PATIENTS
      AND METHODS: A total of 474 unselected patients (58% men; mean age 52 y) were
      included in the study. Two biopsy specimens each were taken from below and above
      the squamocolumnar junction and from the antrum and gastric body. Four-quadrant
      biopsies were taken every 1-2 cm to confirm a macroscopic suspicion of Barrett's
      esophagus. RESULTS: Barrett's esophagus was suspected at endoscopy in 109
      patients (23%). Of the 109 patients with endoscopically suspected Barrett's
      esophagus, only 46 (42%) had the finding confirmed histologically. The
      sensitivity and specificity for the endoscopic diagnosis of Barrett's esophagus
      were 62% and 84%, respectively. A multivariate logistic regression analysis
      identified age (P = 0.0001; odds ratio per life-year 1.087; 95% CI, 1.046-1.139),
      male sex (P = 0.0020; OR 6.346; 95% CI, 2.094-22.314), and the number of biopsies
      (P = 0.0025; OR 1.661; 95% CI, 1.247-2.392) as factors associated with evidence
      of intestinal metaplasia on biopsy. CONCLUSION: The striking discrepancy between
      the endoscopic findings and the histological diagnosis may be due to the focal
      distribution of intestinal metaplasia. This emphasizes the importance of an
      adequate biopsy protocol. In addition, better methods of detecting focal islands
      of intestinal metaplasia that are not visible at conventional endoscopy are
      needed.

PMID- 16281147
TI  - Feasibility of endoscopic ultrasound-guided OncoGel (ReGel/paclitaxel) injection
      into the pancreas in pigs.

PMID- 16281148
TI  - Single-dose brachytherapy for the palliative treatment of esophageal cancer.

PMID- 16281149
TI  - Small-intestinal pathology on capsule endoscopy: miscellaneous.

PMID- 16281150
TI  - Modified rendezvous technique for bilateral biliary drainage through a jejunal
      interponat of the common bile duct with anastomotic strictures.

PMID- 16281151
TI  - A new method of endoscopic submucosal dissection using submucosal injection of
      jelly.

PMID- 16281152
TI  - A new approach to the bile duct via needle puncture of the papillary roof.

PMID- 16281153
TI  - Acute pancreatitis and acute cholecystitis caused by hemobilia after percutaneous
      ultrasound-guided liver biopsy.

PMID- 16281154
TI  - Recurrent rectal bleeding from an appendiceal stump granuloma: a rare late
      complication of appendectomy.

PMID- 16281155
TI  - Ileal ascariasis detected by magnified terminal ileoscopy.

PMID- 16281156
TI  - [Management of hypertension in upheaval?].

PMID- 16281157
TI  - [Results of the "Health Program Hypertension" of the German Health Insurance
      (DKV)].
AB  - BACKGROUND AND OBJECTIVE: In 2003 the German Health Insurance (DKV: Deutsche
      Krankenversicherung) initiated a "Health Program Hypertension" for its insured
      persons with the aim of motivating patients to adopt the accepted general
      measures for blood pressure reduction and to self-monitor their blood pressure.
      PATIENTS AND METHODS: Participation in the program was voluntary and without
      charge. The interventional measures included regular contact by phone with
      trained medical personnel, personal consultations targeting general measures and
      self measurement of blood pressure. Each patient was given training material and
      a blood pressure monitor, and a risk profile was made for each patient. Regular
      reports were given to the patients and their physicians. RESULTS: The data of the
      first 1373 hypertensives who have been in the continuing program were analysed.
      The patients" average age was 61+/-9.9 years, 81% males. 94% of the participants
      reported taking antihypertensive medication. Initially 615 patients (44.8%) had
      an increased blood pressure on self-measurement ((3)135/85 mmHg). The blood
      pressure of these patients was significantly reduced, after an average of 16.3
      months, from 145/91+/-12.7 mmHg to 135/84 +/-12.8 mmHg (p<0.001). A statistically
      significant weight reduction was achieved in 308 patients (22.4%) with a body
      mass index (BMI) of (3) 30 kg/m2, from 33.4 to 32.9 kg/m2 (p<0.001). Lipid
      metabolism, important life-style parameters (food and physical activity) and a
      knowledge of important laboratory tests (glucose and creatinine) also changed
      positively. Antihypertensive medication remained nearly unchanged during the
      period of observation. CONCLUSIONS: The patients participating in the Health
      Program Hypertension were already reasonably well controlled. The program
      achieved further lasting improvement of blood pressure. In addition the
      participants were motivated to adopt a more health-conscious life style. Training
      and care of the patients by a medical services centre would seem sensible and
      successful. But it remains a challenge, especially to reach poorly controlled
      hypertensives and to motivate them to an active participation in the program.

PMID- 16281160
TI  - [U-shaped relationship between nocturnal blood pressure and organ impairment].

PMID- 16281159
TI  - [Endothelial ion channels -- novel targets for antihypertensive therapy].
AB  - Endothelial cation channel are important regulators of vascular tone by
      modulating intracellular Ca(2+)-signaling and thus adequate synthesis of
      vasodilating factors. The overall importance of these ion channels suggests that
      they may represent novel pharmacotherapeutic targets in addition to the well
      known voltage-gated calcium channels in vascular smooth muscle. In this short
      overview we summarize the current knowledge about endothelial ion channels and
      their roles for endothelium-dependent vasodilatation. Furthermore, we
      perspectively discuss the usefulness of specific openers of endothelial Ca(2+)
      activated K(+)-channels and TRPV-channels as novel antihypertensive drugs.

PMID- 16281161
TI  - [Therapy of obesity-associated hypertension].
AB  - There is a 50 % prevalence of obesity with arterial hypertension. This ratio can
      increase up to 80 %, depending on body mass index. Important pathogenetic origins
      are quantity of visceral body fat along with the activation of neuroendocrineum
      (sympathicus, renin-angiotensin system), an induction of insulin resistance with
      hyperinsulinemia, and a direct compression of the medulla by fat deposits in the
      kidneys, which results in hemodynamic changes and an increase in blood pressure.
      The primary aim is a reduction in weight by means of a balanced diet and life
      style modification, which can be augmented by weight reducing medication.
      Orlistat lowers blood pressure and body weight simultaneously, whereas
      sibutramine accomplishes this only under certain circumstances. Interestingly,
      blood pressure increases again over the course of 10 years following weight
      reducing surgical procedures, despite ongoing weight loss. Antihypertensive
      differential therapy should be focused on pathophysiology and concomitant and
      target organ disease. Thus ACE inhibitors (alternatively angiotensin receptor
      blockers), in combination with low dose diuretics, should be preferentially
      administered, followed by calcium antagonists. Beta blockers should be used if
      definite cardiac indications are present.

PMID- 16281162
TI  - [Isolated systolic hypertension].

PMID- 16281163
TI  - [Large artery wall properties -- what is relevant for the classic management of
      hypertension?].
AB  - Decisions about the management of patients with hypertension should not be based
      on the level of blood pressure alone but also on the presence of target organ
      damage. Apart of classical sites of target organ damage - kidney and heart - the
      assessment of functional and structural alterations of large arteries is of
      increasing clinical importance. Modern non-invasive procedures allow the
      assessment of large artery wall properties within the clinical routine.
      Hypertension associated large artery damage may present as structural and
      functional alterations. Structural alterations comprise intima-media thickening,
      plaque formation, stenosis of the artery and formation of aneurysms. Functional
      alterations comprise endothelial dysfunction and alterations of the mechanical
      properties of the arterial wall with increasing stiffness and loss of the
      Windkessel function. Loss of central artery elastic properties will ensue an
      early reflection of the pulse wave with a resulting increase in central systolic
      and central diastolic pressure. This causes an increase in left ventricular
      afterload and a reduction in diastolic perfusion of the myocardium. In the last
      decade the relevance of large artery structural alterations, endothelial
      dysfunction and arterial stiffness for the risk of cardiovascular morbidity and
      mortality in hypertensive patients could be demonstrated convincingly.
      Measurement of intima-media-thickness therefore is part of the standard
      evaluation of hypertensive patients. Because of the equal prognostic relevance of
      functional properties of the arterial wall, assessment of large artery functional
      alterations is helpful for the risk stratification of hypertensive patients.
      Modern antihypertensive drugs have favourable effects on arterial wall
      properties. Therefore, the quantification of large artery wall properties should
      be part of the management of hypertensive patients.

PMID- 16281164
TI  - [Treatment of high blood pressure in acute stroke -- pro].

PMID- 16281165
TI  - [Treatment of high blood pressure in acute stroke -- contra].

PMID- 16281166
TI  - [Twenty-four hour ambulatory blood pressure monitoring].

PMID- 16281167
TI  - cdx4/lacZ and cdx2/lacZ protein gradients formed by decay during gastrulation in
      the mouse.
AB  - Expression of the mouse caudal genes cdx4 and cdx2 is examined by use of lacZ
      reporter constructs expressed in transgenic mouse embryos. During early
      gastrulation, up to at least 8.5 days of development, reporter mRNA distributions
      are apparently similar to those of endogenous cdx mRNAs. By 8.25 to 8.8 days,
      cdx/lacZ protein activities have become distributed as posterior-to-anterior
      gradients along the neural and mesoderm tissues. The gradients form by decay of
      activity as cells become distanced from the regressing tailbud. In situ
      hybridization studies indicate that the decay is primarily in cdx/lacZ protein
      activities rather than mRNAs. As gastrulation proceeds, the locations of the
      gradients regress progressively posteriorly along the growing axis. Our results
      indicate how cdx4 and cdx2 protein gradients might be generated by decay during
      normal development. The smoothness of the gradients that we detect shows that
      there cannot be extensive mixing of cells once they leave the tailbud to
      contribute to the growing axis. An enhancer element located in the first intron
      of the cdx4 gene is essential for correct transgene expression.

PMID- 16281168
TI  - Mouse chimaeras developed from electrofused blastocysts: new evidence for
      developmental plasticity of the inner cell mass.
AB  - Blastocysts obtained from mice differing in pigmentation (albino versus
      pigmented) and the isoforms of glucose phosphate isomerase (GPI 1A versus 1B)
      were electrofused and those containing a single chimaeric inner cell mass (ICM)
      were transferred to the uterus of pseudopregnant recipients. The pups were
      recovered on the 20(th) day by Caesarian section and fostered by females that had
      littered on the previous night or 24 h earlier. Altogether nine adult animals and
      two pups, which died soon after delivery, were available for GPI analysis.
      Between 9 and 13 organs/tissues were examined and the relative contribution of
      the GPI 1A and 1B isoforms was estimated using an electrophoretic GPI assay.
      Eight adult animals were overtly chimaeric and one was chimaeric in some internal
      tissues only. Eight mice were males: seven were fertile, one was infertile. The
      ninth adult mouse was a hermaphrodite. The fertile animals produced sperm of one
      genotype only, i.e. derived either from the albino or from the pigmented
      component. This is the first report showing that adult chimaeras can be produced
      from two combined blastocysts, provided that fusion of the adhering trophectoderm
      cells is first induced and the orientation of blastocysts enables the two ICMs to
      integrate into a single ICM. Our results suggest that in the preimplantation
      blastocyst, the organisation of the ICM remains labile thus making it possible
      for the fused blastocysts to establish new embryonic organisation and to develop
      into a single organism.

PMID- 16281169
TI  - Expression of regulatory genes for pancreas development during murine embryonic
      stem cell differentiation.
AB  - Insulin-producing cells derived from embryonic stem cells could be surrogates for
      beta cells in diabetes therapy. However, their derivation remains hard to achieve
      with current protocols which rely on initial embryoid body formation. We assume
      that factors known to inhibit pancreas development contribute to this limitation
      in vitro. To evaluate this hypothesis, embryoid bodies were examined after
      different culture periods by real time RT-PCR to profile the expression of genes
      known to regulate embryonic pancreas development. Our data indicate that
      transcripts for pancreas markers (insulin, glucagon and amylase ) were expressed
      during differentiation, but the highest levels achieved were at least 10(5) times
      lower than in the adult mouse pancreas. Notch signalling was activated as
      suggested by Delta, Jagged, Ngn3 and NeuroD1 profiles. However, Sonic hedgehog, a
      known inhibitor of pancreas induction in vivo drastically increased in day 6
      embryoid bodies, while Inhibin betaA and betaB were down-regulated and
      follistatin up-regulated. Members of the Fibroblast- and Transforming Growth
      Factor families which pattern the endoderm were expressed at low levels, while
      those that inhibit pancreas development were highly transcribed. The profile of
      pancreas regulators expressed in embryoid bodies is therefore not compatible with
      differentiation of pancreatic and insulin-producing cells. These findings provide
      an explanation for the limited derivation of such cells to date, in addition to
      basic information for establishing novel differentiation protocols.

PMID- 16281170
TI  - Xenopus nodal related-1 is indispensable only for left-right axis determination.
AB  - In Xenopus, multiple nodal-related genes are expressed in the organizer region.
      Among them, only Xenopus nodal related-1 (Xnr-1) is expressed unilaterally in the
      left lateral plate mesoderm (LPM) at late neurula-early tailbud stage. To
      elucidate the essential role of Xnr-1 for left-right specification, loss of
      function experiments using antisense morpholino oligonucleotides (MOs) targeting
      three different regions of Xnr-1 were performed. Left-side injection of Xnr-1 MO
      suppresses the left-side specific genes such as Xnr-1, Xenopus antivin (lefty)
      and Xenopus pitx2 and randomizes cardiac and visceral left-right orientation. In
      contrast, paraxial bilateral expression of Xnr-1 along the posterior notochord is
      not affected by the Xnr-1 MO. In embryos injected with the Xnr-1 MO, morphology
      of dorsal axial structures is normal and dorsal expression of sonic hedgehog and
      TGF-beta5 is not changed. Right-side injection of Nodal protein, or
      polyethyleneimine-based gene transfer of Xnr-1 mRNA in the right LPM induces Xnr
      1 and pitx2 in the same side and fully (more than 90%) reverses situs of the
      internal organs. Left-side injection of Nodal protein restores normal left-right
      orientation in the embryos that were injected with Xnr-1 MO into the left
      blastomere and would cause randomization of the left-right axis without the Nodal
      injection. Taken together, unilateral expression of Xnr-1 in the left LPM directs
      the orientation of the left-right axis by driving the left-specific gene cascade.
      Knockdown of Xnr-1 function by the MOs suggests that Xnr-1 is indispensable only
      for the left-right orientation and dispensable for other embryonic axes probably
      owing to the redundancy in the function of multiple Xnrs.

PMID- 16281171
TI  - Systematic screening for genes specifically expressed in the anterior
      neuroectoderm during early Xenopus development.
AB  - A cDNA library derived from the anterior neuroectoderm (ANE) of Xenopus late
      gastrula embryos was systematically screened to isolate novel developmental
      regulatory genes involved in early brain development. We isolated 1,706 5
      expressed sequence tags (ESTs), which were subdivided into 1,383 clusters and
      categorized into 19 classes based on predicted functions according to their
      similarities to other known genes. Of these, 757 clusters that were considered
      possible novel regulatory genes or unknown genes were subjected to expression
      pattern analysis using whole-mount in situ hybridization. Genes from 69 clusters
      (9%) were expressed in the ANE region. Based on their expression patterns and
      predicted amino acid sequences, 25 genes were selected for further analysis as
      novel Xenopus genes expressed broadly or region-specifically in the ANE. Eighteen
      genes were expressed in postulated patterning centers in the neuroectoderm,
      including the anterior (four genes) and lateral (nine genes) neural ridges, the
      midbrain-hindbrain boundary region (one gene) and the midline region of the
      neural plate (two genes), whereas 13 genes were expressed in the eye anlagen.
      Therefore, early regionalization of the neuroectoderm appears to occur mainly in
      those neural patterning centers and the eye anlagen. We determined the entire
      coding regions of p54nrb, Semaphorin 6D and a novel gene designated scribble
      related protein 1 (SCRP1). Interestingly, Semaphorin 6D is expressed in the
      mesoderm with a dorsoventral gradient, as well as in the ectoderm at the gastrula
      stage, implying a new role for this protein in development other than in axon
      guidance.

PMID- 16281172
TI  - Involvement of Hex in the initiation of feather morphogenesis.
AB  - In a previous study, we showed that the proline-rich divergent homeobox gene
      Hex/Prh is expressed in dorsal skin of the chick embryo before and during feather
      bud development and that the pattern of Hex mRNA expression in the epidermis is
      similar to that of Wnt7a mRNA. In order to study the function of Hex and the
      relationship between Hex and Wnt7a in feather bud development, sense and/or
      antisense sequences of Hex or Wnt7a were ectopically and transiently expressed in
      the dorsal skin with the epidermal side toward the cathode by electroporation at
      the placode stage and then the skin was cultured. Increased expression of Wnt7a
      and beta-catenin mRNA was observed in the same region where Hex-EGFP fusion
      protein was expressed 2 days after culture, which was followed by extra bud
      formation a few days later as a result of the stimulation of cell proliferation.
      Concomitantly, expression of Notch1 mRNA, which is expressed in normal bud
      development, increased in Hex-overexpressing skin. However, ectopic Wnt7a
      expression induced neither Hex expression nor extra bud formation in normal skin.
      Antisense Wnt7a specifically inhibited bud initiation in Hex-overexpressing skin
      but did not in normal skin. Taken together, these results suggest that Hex is
      upstream of Wnt7a and beta-catenin and regulates the Wnt signaling pathway in
      feather bud initiation and that some other Wnt signals in addition to Wnt7a may
      be required for bud initiation.

PMID- 16281173
TI  - The homeobox gene Msx in development and transdifferentiation of jellyfish
      striated muscle.
AB  - Bilaterian Msx homeobox genes are generally expressed in areas of cell
      proliferation and in association with multipotent progenitor cells. Likewise,
      jellyfish Msx is expressed in progenitor cells of the developing entocodon, a
      cell layer giving rise to the striated and smooth muscles of the medusa. However,
      in contrast to the bilaterian homologs, Msx gene expression is maintained at high
      levels in the differentiated striated muscle of the medusa in vivo and in vitro.
      This tissue exhibits reprogramming competence. Upon induction, the Msx gene is
      immediately switched off in the isolated striated muscle undergoing
      transdifferentiation, to be upregulated again in the emerging smooth muscle cells
      which, in a stem cell like manner, undergo quantal cell divisions producing two
      cell types, a proliferating smooth muscle cell and a differentiating nerve cell.
      This study indicates that the Msx protein may be a key component of the
      reprogramming machinery responsible for the extraordinary transdifferentation and
      regeneration potential of striated muscle in the hydrozoan jellyfish.

PMID- 16281174
TI  - A newly discovered oxidant defence system and its involvement in the development
      of Aurelia aurita (Scyphozoa, Cnidaria): reactive oxygen species and elemental
      iodine control medusa formation.
AB  - In Aurelia aurita, applied iodine induces medusa formation (strobilation). This
      process also occurs when the temperature is lowered. This was found to increase
      oxidative stress resulting in an increased production of iodine from iodide. One
      polyp produces several medusae (initially termed ephyrae) starting at the polyp's
      oral end. The spreading of strobilation down the body column is controlled by a
      feedback loop: ephyra anlagen decrease the tyrosine content in adjacent polyp
      tissue by producing melanin from tyrosine. Endogenous tyrosine is able to remove
      iodine by forming iodiferous tyrosine compounds. The reduced level of tyrosine
      causes the ephyra-polyp-border to move towards the basal end of the former polyp.
      We argue that an oxidant defence system may exist which makes use of iodide and
      tyrosine. Like other marine invertebrates, polyps of Aurelia contain iodide ions.
      Inevitably produced peroxides oxidise iodide into iodine. The danger to be harmed
      by iodine is strongly decreased by endogenous tyrosine which reacts with iodine
      to form iodiferous tyrosine compounds including thyroxin. Both substances
      together, iodide and tyrosine, form an efficient oxidant defence system which
      shields the tissue against damage by reactive oxygen species. In the course of
      evolution (from a species at the basis of the animal kingdom like Aurelia to a
      highly evolved species like man) the waste product thyroxin (indicating a high
      metabolic rate) has developed into a hormone which controls the metabolic rate.

PMID- 16281175
TI  - A simple in vivo approach to investigate invasive trophoblast cells.
AB  - Intrauterine trophoblast cell invasion is an essential part of hemochorial
      placentation. Aberrant trophoblast cell invasion has been associated with
      pathologies including preeclampsia and fetal growth restriction. In this study,
      we describe an in vivo method to assess trophoblast cell invasion using a
      transgenic rat model, constitutively expressing heat stable human placental
      alkaline phosphatase (Rosa 26 promoter driven human placental alkaline
      phosphatase, R26-hAP). Wild-type female Fischer 344 inbred rats were mated with
      hemizygous R26-hAP transgenic male Fischer 344 rats and sacrificed during the
      second half of pregnancy. Heat stable alkaline phosphatase (AP) activity
      associated with the invasive transgenic trophoblast cells was monitored in the
      wild-type uterine mesometrial compartment and used as an index of trophoblast
      cell invasion. The expression pattern of cytokeratins by invasive trophoblast
      cells mimicked the uterine mesometrial distribution of AP activity. Trophoblast
      cell invasion exhibited a gestation-dependent profile with peak invasion between
      days 18-20 of pregnancy. In summary, we have devised a simple in vivo method for
      assessing intrauterine trophoblast cell invasion. This technique should
      facilitate the discovery of endogenous regulatory mechanisms controlling
      trophoblast cell invasion and should represent an effective method of testing the
      impact of various environmental stressors on an essential part of hemochorial
      placentation.

PMID- 16281176
TI  - Developmental expression of Xenopus fragile X mental retardation-1 gene.
AB  - Dysregulation of Fragile X mental retardation-1 (Fmr1) gene expression results in
      an inherited form of mental retardation known as the Fragile X syndrome (FXS).
      Fmr1 is a highly conserved gene with a broad yet distinctive expression pattern
      during vertebrate development. Here, we examined the expression pattern of Fmr1
      during Xenopus embryonic development. Zygotic expression of Fmr1 began just prior
      to gastrulation and gradually increased during subsequent embryonic stages. By in
      situ hybridization, Fmr1 transcripts were detected by early tailbud stage and
      showed robust expression in the central nervous system (CNS), eye and pharyngeal
      arches. By late tailbud stage, Fmr1 expression became stronger in the CNS and
      craniofacial regions including the ear vesicle and eye. In addition, the
      notochord expressed high levels of Fmr1 transcripts in the late tailbud stage
      embryos. In the tadpole brain, the olfactory bulb and cerebellum exhibited strong
      Fmr1 expression. The developmental expression pattern of Fmr1 is consistent with
      the wide range of abnormalities observed in FXS. Further, our findings indicate
      that Xenopus will serve as an excellent model to study the developmental basis of
      this disease.

PMID- 16281177
TI  - Isolation and proteomic analysis [corrected] of cell wall-deficient Haematococcus
      pluvialis mutants.
AB  - The green alga Haematococcus pluvialis has a plant-like cell wall consisting of
      glycoproteins and cellulose that is modified during the cell cycle and under
      various conditions. These features allow Haematococcus to be used as a model
      organism for studying cell wall biology. Development of the Haematococcus model
      is hampered by the absence of mutants that could provide insight into the
      biosynthesis and assembly of wall components. Haematococcus mutants (WM#537 and
      WM#2978) (WM--wall mutant) with defective cell walls were obtained by chemical
      mutagenesis. WM#537 features a secondary wall of considerably reduced thickness,
      whereas WM#2978 possesses a somewhat reduced secondary wall with little
      intervening space between the wall and plasmalemma. 2-DE revealed that a majority
      of the cell wall proteins were present in the wild-type and mutant cell walls
      throughout the cell cycle. PMF identified 55 wall protein orthologs from these
      strains, including a subset of induced proteins known to be involved in wall
      construction, remodeling, and defense. Down-regulation of certain wall proteins
      in the two mutants was associated with the wall defects, whereas overexpression
      of other proteins may have compensated for the defective walls in the two
      mutants.

PMID- 16281178
TI  - Immunoproteomics of outer membrane proteins and extracellular proteins of
      Shigella flexneri 2a 2457T.
AB  - Shigella flexneri 2a is an important pathogen causing bacillary dysentery in
      humans. In order to investigate any potential vaccine candidate proteins present
      in outer membrane proteins (OMPs) and extracellular proteins of S. flexneri 2a
      2457T, we use the proteome mapping and database analyzing techniques. A
      subproteome map and database of OMPs were established first. One hundred and nine
      of the total 126 marked spots were cut out and processed to MALDI-TOF-MS and PMF.
      Eighty-seven spots were identified and they represented 55 OMP entries.
      Furthermore, immunoproteomics analysis of OMPs and extracellular proteins were
      performed. Total of 34 immunoreactive spots were identified, in which 22 and 12
      were from OMPs and extracellular proteins, respectively. Eight novel antigens
      were found and some of these antigens may be potential vaccine candidate
      proteins. These results are useful for future studying of pathogenicity, vaccine,
      and novel antibacterial drugs. Maps and tables of all identified proteins are
      available on the Internet at www.proteomics.com.cn.

PMID- 16281179
TI  - Glycomic/glycoproteomic analysis by liquid chromatography/mass spectrometry:
      analysis of glycan structural alteration in cells.
AB  - The alteration of glycosyltransferase expression and the subsequent changes in
      oligosaccharide structures are reported in several diseases. The analysis of
      glycan structural alteration in glycoproteins is becoming increasingly important
      in the discovery of therapies and diagnostic markers. In this study, we propose a
      strategy for glycomic/glycoproteomic analysis based on oligosaccharide profiling
      by LC/MS followed by proteomic approaches, including 2-DE and 2-D lectin blot. As
      a model of aberrant cells, we used Chinese hamster ovary cells transfected with N
      acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of a
      bisecting N-acetylglucosamine (GlcNAc) to beta-mannose of the mannosyl core of N
      linked oligosaccharides. LC/MS equipped with a graphitized carbon column (GCC)
      enabled us to elucidate the structural alteration induced by the GnT-III
      expression. Using 2-D lectin blot followed by LC/MS/MS, the protein carrying an
      extra N-acetylhexosamine in cells transfected with GnT-III was successfully
      identified as integrin alpha3. Thus, oligosaccharide profiling by GCC-LC/MS
      followed by proteomic methods can be a powerful tool for glycomic/glycoproteomic
      analysis.

PMID- 16281180
TI  - Albumin depletion of human plasma also removes low abundance proteins including
      the cytokines.
AB  - The use of proteomics for efficient, accurate, and complete analysis of clinical
      samples poses a variety of technical challenges. The presence of higher abundance
      proteins in the plasma, such as albumin, may mask the detection of lower
      abundance proteins such as the cytokines. Methods have been proposed to deplete
      the sample of these higher abundance proteins to facilitate detection of those
      with lower abundance. In this study, a commercially available albumin depletion
      kit was used to determine if removal of albumin would measurably reduce detection
      of lower abundance cytokine proteins in human plasma. The Montage Albumin Deplete
      Kit (Millipore) was used to deplete albumin from LPS-stimulated whole blood from
      15 normal human donors. Albumin depletion was measured using the BCG reagent and
      SDS-PAGE, and cytokine recovery was determined by a microassay immunoassay that
      measures both pro- and anti-inflammatory cytokines. Average albumin depletion
      from the samples was 72%. However, several cytokines were also significantly
      reduced when the albumin was removed from the plasma. Additionally, there was a
      variable reduction in cytokine recovery from a known mixture of cytokines in a
      minimal amount of plasma that were loaded onto the columns. These data
      demonstrate that there may be a non-specific loss of cytokines following albumin
      depletion, which may confound subsequent proteomic analysis.

PMID- 16281181
TI  - Human urine proteome analysis by three separation approaches.
AB  - The urinary proteome is known to be a valuable field of study related to organ
      functions. There have been several extensive urine proteome studies. However, the
      overlapping rate among different studies is relatively low. Whether the low
      overlapping rate was caused by different sample sources, preparation, separation
      and identification methods is unknown. Moreover, low molecular mass (<10 kDa)
      proteins have not been studied extensively. In this report, male and female
      pooled urine samples were collected from healthy volunteers. The urinary proteins
      were acetone precipitated, separated and identified by three approaches, 1-DE
      plus 1-D LC/MS/MS, direct 1-D LC/MS/MS and 2-D LC/MS/MS. 1-D tricine gels were
      used to separate low molecular mass proteins. The tandem mass spectra of positive
      identifications were quality controlled both by manual validation and using
      advanced mass spectrum scanner software. A total of 226 urinary proteins were
      identified; 171 proteins were identified by proteomics approach for the first
      time, including 4 male-specific proteins. Twelve low molecular mass proteins were
      identified. Most urinary proteins had a molecular mass between 30 and 60 kDa and
      a pI between 4 and 10. The apparent molecular masses of many proteins were
      different from theoretical ones, which indicated their post-translational
      modification and degradation. The effects of sample preparation, separation and
      identification methods on the overlapping rate of different experiments are
      discussed.

PMID- 16281182
TI  - Proteomics-based analysis of a counter-oxidative stress system in Porphyromonas
      gingivalis.
AB  - Porphyromonas gingivalis is a Gram-negative anaerobic pathogen associated with
      chronic periodontitis. Although anaerobic, P. gingivalis exhibits a high degree
      of aerotolerance, which enables it to survive within periodontal pockets. The aim
      of the present study was to examine the effect of oxidative stress on protein
      expression in P. gingivalis to obtain a better understanding of the mechanism
      underlying its aerotolerance. To accomplish this, P. gingivalis cells were grown
      under conditions of hemin limitation (0.01 microg/mL) to avoid the oxygen
      protective effect of hemin on oxidative stress. The proteins were then extracted
      from cultures either left untreated or subjected to oxidative stress and
      separated by 2-DE. The resultant protein expression profiles were examined by
      image scanning, and those found to differ depending on the presence or absence of
      aeration were subjected to MALDI-MS and then analyzed using the ORF database of
      P. gingivalis W83 from The Institute of Genomic Research. Oxidative stress was
      found to affect the expression of numerous proteins in P. gingivalis cells. In
      particular, the levels of HtpG, GroEL, DnaK, AhpC, TPR domain protein, and
      trigger factor were substantially increased.

PMID- 16281183
TI  - A study of Streptococcus thermophilus proteome by integrated analytical
      procedures and differential expression investigations.
AB  - Streptococcus thermophilus is a Gram-positive bacterium belonging to the group of
      lactic acid bacteria, among which several genera play an essential role in
      manufacture of food products. Recently, a genomic consortium sequenced and
      annotated its entire genome, which has been demonstrated to contain 1900 coding
      sequences. In this study, we have revealed the expression products of almost 200
      different genes using a proteomic strategy combining 2-DE plus MALDI-TOF PMF and
      differential 1-DE plus muLC-ESI-IT-MS/MS. Thus, a number of cellular pathways
      related to important physiological processes were described at the proteomic
      level. Almost 50 genes were related to multiple electrophoretic species, whose
      heterogeneity was mainly due to variability in pI values. A 2-DE reference map
      obtained for lactose-grown cells was compared with those obtained after heat,
      cold, acid, oxidative and starvation stresses. Protein up/down-regulation
      measurements demonstrated that adaptation to different environmental challenges
      may involve the contribution of unique as well as combined physiological
      mechanisms. Common regulatory sites in the promoter region of genes whose
      expression was induced after stress were identified. These results provide a
      better comprehension of biochemical processes related to stress resistance in S.
      thermophilus, allowing defining the molecular bases of adaptative responses or
      markers for the identification of strains with potential industrial applications.

PMID- 16281184
TI  - The secretome of Pleurotus sapidus.
AB  - Due to their unique capability to attack lignified biopolymers, extracellular
      enzymes of white-rot fungi enjoy an increasing interest in various fields of
      white biotechnology. The edible fungus Pleurotus sapidus was selected as a model
      organism for the analysis of the secretome by means of 2-DE. For enzyme
      production, the fungus was grown in submerged cultures either on peanut shells or
      on glass wool as a carrier material. Identification of the secreted enzymes was
      performed by tryptic digestion, ESI-MS/MS ab initio sequencing, and homology
      searches against public databases. The spectrum of secreted enzymes comprised
      various types of hydrolases and lignolytic enzymes of the manganese
      peroxidase/versatile peroxidase family. While peptidases were secreted mainly by
      the cultures grown on peanut shells, versatile peroxidase type enzymes dominated
      in the cultures grown on glass wool.

PMID- 16281185
TI  - Pathogen elicitor-induced changes in the maize extracellular matrix proteome.
AB  - The extracellular matrix is a vital compartment in plants with a prominent role
      in defence against pathogen attack. Using a maize cell suspension culture system
      and pathogen elicitors, responses to pathogen attack that are localised to the
      extracellular matrix were examined by a proteomic approach. Elicitor treatment of
      cell cultures induced a rapid change in the phosphorylation status of
      extracellular peroxidases, the apparent disappearance of a putative extracellular
      beta-N-acetylglucosamonidase, and accumulation of a secreted putative xylanase
      inhibitor protein. Onset of the defence response was attended by an accumulation
      of glyceraldehyde-3-phosphate dehydrogenase and a fragment of a putative heat
      shock protein. Several distinct spots of both proteins, which preferentially
      accumulated in cell wall protein fractions, were identified. These three novel
      observations, viz. (i) secretion of a new class of putative enzyme inhibitor,
      (ii) the apparent recruitment of classical cytosolic proteins into the cell wall
      and (ii) the change in phosphorylation status of extracellular matrix proteins,
      suggest that the extracellular matrix plays a complex role in defence. We discuss
      the role of the extracellular matrix in signal modulation during pathogen-induced
      defence responses.

PMID- 16281186
TI  - High-throughput MS-based protein phenotyping: application to haptoglobin.
AB  - A high-throughput affinity capture and reduction approach was developed for
      phenotype and post-translational modification analysis of a complexed globular
      protein, haptoglobin (Hp), directly from human plasma. Hp was selectively
      retrieved utilizing anti-Hp antibodies immobilized onto affinity pipette tips,
      eluted onto a formatted mass spectrometer target for reduction of Hp alpha-chains
      (Hpalpha1 and Hpalpha2) and subjected to subsequent MALDI-MS analysis. The
      affinity capture and reduction approach was originally developed from a pre
      extraction reduction methodology that was optimized to an affinity capture post
      reduction technique for intact Hp alpha-chain variant analysis, phenotype
      classification and ensuing post-translational variant detection. Three common Hp
      phenotypes (1-1, 2-1 and 2-2) were assigned according to detection of Hpalpha1
      and/or Hpalpha2 reduced intact chain(s) average mass(es). The affinity capture
      post-reduction approach was scaled for high-throughput Hp alpha-chain phenotype
      analysis from a normal plasma cohort. The entire sample cohort was successfully
      analyzed and phenotyped using the developed approach. Additionally, Hp post
      translational variants were detected and assigned via accurate MS analyses. The
      results of this study suggest use of the methodology in future analyses of other
      similarly complexed proteins and in normal versus disease cohort population
      proteomics studies.

PMID- 16281187
TI  - Virtual identification of essential proteins within the protein interaction
      network of yeast.
AB  - Topological analysis of large scale protein-protein interaction networks (PINs)
      is important for understanding the organizational and functional principles of
      individual proteins. The number of interactions that a protein has in a PIN has
      been observed to be correlated with its indispensability. Essential proteins
      generally have more interactions than the nonessential ones. We show here that
      the lethality associated with removal of a protein from the yeast proteome
      correlates with different centrality measures of the nodes in the PIN, such as
      the closeness of a protein to many other proteins, or the number of pairs of
      proteins which need a specific protein as an intermediary in their
      communications, or the participation of a protein in different protein clusters
      in the PIN. These measures are significantly better than random selection in
      identifying essential proteins in a PIN. Centrality measures based on graph
      spectral properties of the network, in particular the subgraph centrality, show
      the best performance in identifying essential proteins in the yeast PIN. Subgraph
      centrality gives important structural information about the role of individual
      proteins, and permits the selection of possible targets for rational drug
      discovery through the identification of essential proteins in the PIN.

PMID- 16281188
TI  - The European Proteomics Association (EuPA) is in the field. Report of the formal
      inauguration of the European Proteome Association (Munich, Germany, August 29,
      2005).
AB  - After one year of preparation the European Proteomics Association (EuPA) was
      formally inaugurated on August 29, 2005, on the occasion of the 4(th) HUPO World
      Congress in Munich, Germany. Delegates from 16 European countries elected Dr.
      Friedrich Lottspeich, President of the German Proteome Society, as the first EuPA
      President. The EuPA Board also comprises Professor Mathias Uhlen as Vice
      President, along with Professor Michael Dunn (Ireland), Professor Concha Gil
      (Spain), Dr. Jean Charles Sanchez (Switzerland) and Professor Pier Giorgio
      Righetti (Italy) as Coordinators for the presently defined focus activities of
      the EuPA. The general objectives of the EuPA are to promote proteomic activities
      throughout Europe, emphasising the benefits and contribution of proteomics to
      biological researchers, industry, the general public and politicians.

PMID- 16281189
TI  - Long-range J(CH) heteronuclear coupling constants in cyclopentane derivatives.
AB  - Detailed measurements of long-range heteronuclear spin-spin coupling constants,
      especially (2, 3)J(CH) spin-spin couplings for various cyclopentane derivatives,
      are reported. The measurements are based on a 2D heteronuclear correlation
      experiment named G-BIRD(R, X)-CPMG-HSQMBC.

PMID- 16281190
TI  - Single-session behavioral treatment of earthquake-related posttraumatic stress
      disorder: a randomized waiting list controlled trial.
AB  - In an attempt to develop a brief treatment for disaster survivors, the present
      study examined the effectiveness of a single session of modified behavioral
      treatment in earthquake-related posttraumatic stress disorder. Fifty-nine
      earthquake survivors in Turkey were randomized into either single-session
      modified behavioral treatment (SSBT) designed to enhance sense of control over
      earthquake-related fears or waiting list control condition (WL). The WL group
      received SSBT after a second baseline assessment. Follow-ups were at weeks 6, 12,
      24, and at 1-2 years posttreatment. Significant treatment effects were found on
      all measures at posttreatment. The improvement rate was 49% at week 6; it rose to
      80% by week 12, 85% by week 24, and 83% by the 1-2-year follow-up. Brief
      behavioral treatment has promise as a cost-effective intervention for disaster
      survivors.

PMID- 16281191
TI  - DESNOS in three postconflict settings: assessing cross-cultural construct
      equivalence.
AB  - This study examined the cross-cultural construct equivalence of the Structured
      Interview for Disorders of Extreme Stress (SIDES), an instrument designed to
      assess symptoms of Disorders of Extreme Stress Not Otherwise Specified (DESNOS).
      Participants completed the SIDES as a part of an epidemiological survey conducted
      between 1997 and 1999 among survivors of war or mass violence in Algeria (n =
      652), Ethiopia (n = 1,200), and Gaza (n = 585). Findings indicated that the
      factor structure of the SIDES across samples was not stable; thus construct
      equivalence was not shown. A multistep interdisciplinary method is proposed to
      improve the cross-cultural construct validity of a psychiatric concept. This
      method accommodates universal chronic sequelae of extreme stress and accommodates
      culture-specific symptoms across a variety of cultures.

PMID- 16281192
TI  - Juvenile conduct disorder as a risk factor for trauma exposure and posttraumatic
      stress disorder.
AB  - Juvenile conduct disorder (CD) is a well-documented risk factor for posttraumatic
      stress disorder (PTSD). This study examines the mechanisms underlying this
      relationship by using data from 3,315 twin pairs in the Vietnam Era Twin
      Registry. Results indicate the number of conduct disorder symptoms increased risk
      of trauma exposure and PTSD in a dose-response fashion. This increased risk was
      mediated in part by the positive association between CD and lifestyle factors and
      was not due to confounding by shared genetic or familial vulnerability. The
      findings suggest CD increases risk for trauma exposure and PTSD among male
      veterans through direct and indirect mechanisms. Veterans who have a history of
      CD are at high risk for trauma exposure and development of PTSD.

PMID- 16281193
TI  - The prevalence of traumatic events in young Japanese women.
AB  - In an effort to address important cross-cultural considerations in the study of
      posttraumatic stress disorder (PTSD), the present study is the first to assess
      the prevalence of a variety of potentially traumatic events among young Japanese
      women across life phases. Overall, our results proved similar to those reported
      in previous Western studies: Traumatic events were quite common among our
      participants (80.3%; n = 883). This finding is not surprising given that many of
      them lived through the 1995 Kobe earthquake. Yet our study found that even when
      "natural disaster" was excluded, the rate remained 53.1%. Comparing four life
      phases, we found the most consistent differences between preschool and other life
      phases. The prevalence of potentially traumatic events and the percentage of most
      distressing events that participants reported were significantly lower in the
      preschool phase.

PMID- 16281194
TI  - Posttraumatic stress, anxiety, and depression in survivors of severe acute
      respiratory syndrome (SARS).
AB  - This study examines the psychological impact of severe acute respiratory syndrome
      (SARS) in 195 adult patients in Hong Kong. The Impact of Event Scale-Revised and
      Hospital Anxiety and Depression Scale were administered to patients 1 month after
      their discharge. Of the participants 10% to 18% reported symptoms related to
      posttraumatic stress disorder, anxiety, and depression. Symptom severity was
      associated with high perceived life threat and low emotional support. Women and
      participants who had low education level were more likely to have symptoms of
      avoidance. Participants who personally knew someone who had SARS were more likely
      to be affected by depressive symptoms.

PMID- 16281195
TI  - Consistency of retrospective reports of DSM-IV criterion A traumatic stressors
      among substance use disorder patients.
AB  - Posttraumatic stress disorder (PTSD) is prevalent among substance use disorder
      (SUD) patients. Although Criterion A trauma is critical to the formulation of a
      PTSD diagnosis, little research has examined the reliability of retrospective
      reports of such stressors and factors that affect reporting among these patients.
      This study examined these issues among SUD patients. Participants (N = 120) were
      assessed by interviews and questionnaires after entering inpatient SUD treatment
      and at a 6-month follow-up. About 40% of participants met criteria for a current
      PTSD diagnosis. Results revealed moderate stability of Criterion A trauma
      reports, which improved when Criterion A requirements were relaxed (i.e.,
      participants were required to report the stressor but not the Criteria A1 and
      A2). Intrusive symptoms were associated with increased stressor reporting over
      time, whereas numbing symptoms and SUD abstinence were associated with decreased
      stressor reporting over time. Dissociative symptoms were associated with changes
      in reporting in either direction.

PMID- 16281196
TI  - Systematic review of screening instruments for adults at risk of PTSD.
AB  - The development of effective methods of screening for posttraumatic stress
      disorder (PTSD) is important in the context of mass trauma, the geographical
      dispersion of victims, and the restricted availability of specialists in
      psychological trauma. The review focused on published English-language screening
      instruments for civilian PTSD consisting of 30 items or fewer and validated
      against structured clinical interviews. Thirteen instruments were identified
      meeting these criteria, all consisting of symptoms of traumatic stress. The
      review concluded that the performance of some currently available instruments is
      near to their maximal potential effectiveness, and that instruments with fewer
      items, simpler response scales, and simpler scoring methods perform as well as if
      not better than longer and more complex measures.

PMID- 16281197
TI  - The use of the trauma symptom inventory in the assessment of PTSD symptoms.
AB  - This study examined the Trauma Symptom Inventory (TSI; Briere, 1995) in a sample
      of 62 trauma-exposed community residents (80% Caucasian, 89% women), including 16
      who had posttraumatic stress disorder (PTSD). PTSD and non-PTSD groups differed
      on seven TSI clinical scales and one validity scale, with effect sizes (r)
      ranging from 0.26 to 0.53. The largest effect sizes and best diagnostic utility
      were found for the Defensive Avoidance and Anxious Arousal scales. Diagnostic
      utility analyses suggest that TSI subscales in isolation are not superior to
      existing measures of PTSD. A logistic regression using the five most
      discriminating TSI scales produced a correct classification rate of 85.5%. TSI
      scales also demonstrated good convergent validity with other measures of PTSD.
      Overall, the results provide preliminary support for the use of the TSI in the
      assessment of PTSD.

PMID- 16281198
TI  - PTSD in former prisoners of war: prewar, wartime, and postwar factors.
AB  - We investigated relationships among prewar, wartime, and postwar factors and
      posttraumatic stress disorder (PTSD) severity in a community sample of 160 former
      prisoners of war (POWs). Data were collected from structured clinical interviews,
      self-report questionnaires, and military service records. POW camp trauma was
      most predictive of PTSD severity, followed by a refined postwar Social Support
      variable: Interpersonal Connection. Prewar conduct disorder behavior was
      positively predictive of PTSD and negatively predictive of Interpersonal
      Connection. Combat exposure and age at capture were also predictive of PTSD.
      Prewar family closeness was not a significant predictor of PTSD but was
      predictive of postwar Interpersonal Connection. This study provides further
      empirical evidence that trauma, when sufficiently severe, is the most significant
      predictor of PTSD severity.

PMID- 16281199
TI  - Capitol hill staff workers' experiences of bioterrorism: qualitative findings
      from focus groups.
AB  - Little systematic information is available on mental health issues related to
      bioterrorism. Five focus groups were conducted with Capitol Hill office staff (n
      = 28 total participants) to learn about their experience of the anthrax incident
      on October 15, 2001. More than 2,000 verbal passages were coded into categories
      and themes by using qualitative analysis software. Issues emerging from the
      discussions included difficulties utilizing customary social supports, concerns
      over potential long-term dangers created by efforts to eradicate the anthrax, and
      nonadherence to antianthrax medication regimens. Nonadherence to antibiotic
      prophylaxis is of immediate concern for response to future bioterrorist events as
      well as infectious disease epidemics. Other topics that warrant attention are
      social support and mental health interventions.

PMID- 16281200
TI  - Secondary traumatic stress among disaster mental health workers responding to the
      September 11 attacks.
AB  - Relationships between secondary traumatic stress (STS) symptoms and therapist
      characteristics and assignment variables were examined for 81 disaster mental
      health (DMH) workers who responded to the terrorist attacks of September 11,
      2001. Higher STS was associated with therapist variables of heavier prior trauma
      caseload, less professional experience, youth, and therapist's discussion of his
      or her own trauma or trauma work in his or her own therapy. Therapist gender and
      personal trauma history were not significantly related to STS. Assignment
      variables associated with higher STS included longer length of assignment and
      more time spent with child clients, firefighters (who suffered great losses in
      the tragedy), or clients who discussed morbid material. Recommendations for
      practice include informing DMH recruits of therapist risk factors and assigning
      at-risk DMH workers to lower-risk assignments.

PMID- 16281201
TI  - Assault, psychiatric diagnoses, and sociodemographic variables in relation to
      help-seeking behavior in a national sample of women.
AB  - Using a national probability household sample of 4,008 women, we estimated the
      prevalence and correlates of formal and informal help seeking. One-year
      prevalences of formal help seeking (e.g., seeking help from professional) and
      informal help seeking (e.g., seeking help from a relative or friend) were 10.6
      and 6.6%, respectively. In the final multivariable model, increased likelihood of
      informal help seeking was associated with younger age, history of sexual assault,
      and past-year diagnoses of posttraumatic stress disorder (PTSD) and major
      depressive episode (MDE). Similarly, increased likelihood of formal help seeking
      was associated with younger age, Caucasian racial/ethnic status, history of
      sexual assault, history of physical assault, and past-year diagnoses of PTSD and
      MDE. Implications for helping professionals and public education programs are
      discussed.

PMID- 16281202
TI  - Physiological arousal and dissociation in acute trauma victims during trauma
      narratives.
AB  - The aim of the present study was to examine whether the finding of suppressed
      physiological activity in dissociative rape-trauma victims (Griffin, Resick, &
      Mechanic, 1997) was replicable in a nonsexual assault trauma group. A sample of
      17 high-dissociating (HD) participants and 18 low-dissociating (LD) participants
      who had experienced a motor vehicle accident or physical assault described their
      trauma while skin conductance, heart rate activity, and self-reported mood were
      recorded. HD individuals demonstrated a trend for elevated heart rate during the
      experiment compared with LD participants, but both groups displayed comparable
      skin-conductance levels. Curve estimation analysis indicated that the two groups
      had a similar pattern of physiological responding during the trauma narratives.
      These findings challenge the notion that dissociative reactions are associated
      with reduced psychophysiological arousal after trauma.

PMID- 16281203
TI  - Deployment stressors, gender, and mental health outcomes among Gulf War I
      veterans.
AB  - Findings indicate that war-zone exposure has negative implications for the
      postdeployment adjustment of veterans; however, most studies have relied on
      limited conceptualizations of war-zone exposure and focused on male samples. In
      this study, an array of deployment stressors that were content valid for both
      female and male Gulf War I military personnel was examined to elucidate gender
      differences in war-zone exposure and identify gender-based differential
      associations between stressors and mental health outcomes. While women and men
      were exposed to both mission-related and interpersonal stressors and both
      stressor categories were associated with mental health outcomes, women reported
      more interpersonal stressors and these stressors generally had a stronger impact
      on women's than on men's mental health. Exceptions are described, and
      implications are discussed.

PMID- 16281204
TI  - Embedded journalists in the Iraq war: are they at greater psychological risk?
AB  - The current war in Iraq saw an alliance between the media and the military, a
      process called embedded journalism. The aim of this study was to explore whether
      this process affected the journalists' vulnerability to psychological distress.
      Eighty-five of 100 journalists approached agreed to participate; 38 (44.7%) were
      embedded. There were no differences between embedded and unilateral (non
      embedded) journalists on demographic measures or in their exposure to traumatic
      events. Similarly, the two groups did not differ on indices of posttraumatic
      stress disorder, depression, psychological distress, and substance use. Based on
      General Health Questionnaire scores, one third of all journalists were
      psychologically distressed. There is no evidence from the recent war in Iraq
      suggesting that embedded journalists are at increased risk for psychological
      problems.

PMID- 16281205
TI  - The role of loss of meaning in the pursuit of treatment for posttraumatic stress
      disorder.
AB  - Clinical observation and theory suggest that people who have difficulty coping
      with their exposure to traumatic events often experience a loss of meaning to
      their lives. This article examines the contribution of loss of meaning to seeking
      help from clergy and/or mental health providers. Results support the hypotheses
      that veterans who have suffered a greater loss of meaning are more likely to seek
      help from clergy and from VA mental health professionals. We suggest that
      veterans who seek help from clergy are particularly desirous of achieving a
      restoration of meaning that is specific to their loss, and that this quest
      sustains a continued pursuit of mental health treatment, especially among those
      who seek help from the VA.

PMID- 16281206
TI  - Motives to drink as mediators between childhood sexual assault and alcohol
      problems in adult women.
AB  - Two models are proposed to relate maladaptive emotion regulation strategies and
      alcohol-related problems for women with a history of childhood sexual assault
      (CSA). The distress coping model suggests only one motive-drinking to cope with
      negative emotions-mediates the relationship between CSA and alcohol problems. The
      emotion regulation model suggests two motives mediate the relationship between
      CSA and alcohol problems: drinking to cope with negative emotions and drinking to
      enhance positive emotions. These models were tested in a random community sample
      of 697 women, ranging from 25 to 75 years old. Both motives partially mediated
      the relationship between CSA and alcohol problems. Effects were small, but
      reliable.

PMID- 16281207
TI  - Correlation between traumatic events and posttraumatic stress disorder among
      North Korean defectors in South Korea.
AB  - The number of North Korean defectors entering South Korea has been increasing
      rapidly since 1994. Two hundred North Korean defectors in South Korea were
      studied to identify their experiences of traumatic events in North Korea and
      during defection, and the correlation with Posttraumatic Stress Disorder (PTSD).
      Researchers conducted face-to-face interviews and assisted defectors in
      performing a self-report assessment of this survey. The study questionnaire
      consisted of demographic characteristics, the Traumatic Experiences Scale for
      North Korean Defectors, and the PTSD part of the Structured Clinical Interview
      for DSM-III-R Korean version. Prevalence rate of PTSD in defectors was 29.5%,
      with a higher rate for women. In factor analysis, the 25 items of traumatic
      events experienced in North Korea were divided into three factors: Physical
      Trauma, Political-Ideological Trauma, and Family-Related Trauma. In addition, the
      19 items of traumatic events during defection were grouped into four factors:
      Physical Trauma, Detection and Capture-Related Trauma, Family-Related Trauma, and
      Betrayal-Related Trauma. In multifactorial logistic regression analysis, Family
      Related Trauma in North Korea had a significant odds ratio.

PMID- 16281208
TI  - Treatment of residual insomnia after CBT for PTSD: case studies.
AB  - Insomnia is one of the most common symptoms of posttraumatic stress disorder
      (PTSD). Evidence suggests that insomnia may persist for many PTSD patients after
      other symptoms have responded to cognitive-behavioral therapy (CBT). The present
      article reports the effects of administering a five-session cognitive-behavioral
      insomnia treatment to 5 patients who responded to CBT for PTSD yet continued to
      report insomnia. Insomnia treatment was associated with improvements on
      subjective sleep measures (Pittsburgh Sleep Quality Index, Insomnia Severity
      Index, and Beliefs and Attitudes about Sleep Scale) and self-monitored sleep
      efficiency and related measures in 4 of 5 cases. Results highlight issues
      specific to treating insomnia in trauma populations and future directions for
      examining treatment of insomnia associated with PTSD.

PMID- 16281209
TI  - Psychometric properties of a Swedish translation of the Clinician-Administered
      PTSD Scale--Diagnostic Version.
AB  - Internal consistency (N = 172) and convergent validity (N = 73) of a Swedish
      translation of the Clinician-Administered PTSD Scale-Diagnostic Version (CAPS-DX)
      were evaluated with violence victims with posttraumatic stress disorder (PTSD).
      The CAPS-DX evidenced a promising internal consistency, and significant
      correlations (Pearson product-moment) with the PTSD Symptom Scale Self-Report
      version (PSS-SR) and the Impact of Event Scale-Revised (IES-R). Additionally,
      each subscale of the CAPS-DX (intrusion, avoidance/numbing, and arousal) was
      significantly correlated with the corresponding subscales of the PSS-SR and the
      IES-R. Results of the present study are discussed in the context of internal
      consistencies and convergent validity coefficients of the CAPS with other PTSD
      symptom measures in previous studies.

PMID- 16281210
TI  - Prediction of numbing and effortful avoidance in female rape survivors with
      chronic PTSD.
AB  - The purpose of the present study was to investigate the relationships among
      numbing, arousal, intrusion, and avoidance in a sample of 272 female rape
      survivors. Multiple regression analyses were conducted to test a theoretical
      model, which posits that hyperarousal and numbing are functionally related
      mechanisms and intrusions and avoidance are functionally related. Results
      supported the hypothesis that arousal explained the majority of the variance in
      numbing beyond that explained by avoidance and intrusion. In addition, intrusive
      symptoms explained the majority of the variance in effortful avoidance beyond
      that explained by numbing and arousal. The findings suggest that numbing and
      effortful avoidance may be separate mechanisms associated with symptoms of
      arousal and intrusion, respectively.

PMID- 16281211
TI  - Role of peer support and emotional expression on posttraumatic stress disorder in
      student paramedics.
AB  - This exploratory study contrasted and tested the predictive value of the reverse
      buffering hypothesis of social support and the information processing model of
      posttraumatic stress disorder (PTSD) in an investigation of trauma-related
      symptomatology (TRS) in a single sample of 42 student paramedics. Participants
      completed several anonymous self-report measures of PTSD symptomatology, peer
      social support, and attitude toward emotional expression. Regression-based path
      analyses did not support either theory of PTSD in this population. A path model
      of PTSD in student paramedics was subsequently developed, indicating that a
      direct relationship exists between duty-related trauma exposure, dysfunctional
      peer social support, and students' negative attitudes toward emotional
      expression. This new model accounted for 30% of the variance in student
      paramedics' TRS.

PMID- 16281212
TI  - Traumatic brain injury, dissociation, and posttraumatic stress disorder in road
      traffic accident survivors.
AB  - This study investigated the symptom profiles of acute stress disorder (ASD) and
      posttraumatic stress disorder (PTSD) in participants who did and did not sustain
      traumatic brain injury (TBI), following a road traffic accident. The participants
      were assessed at three time points: as soon as possible posttrauma as well as at
      6 weeks and 3 months posttrauma. At the first assessment, fewer participants from
      the TBI group recalled feeling fear and helplessness at the time of the trauma,
      fewer TBI participants reported recurrent intrusive thoughts and images, and more
      TBI participants reported dissociation since the trauma, relative to the non-TBI
      group. At the second assessment, fewer participants from the TBI group recalled
      feeling intense helplessness at the time of the trauma. Fewer TBI participants
      also reported reliving and physiological reactions on trauma reminders relative
      to the non-TBI group. At 3 months posttrauma, there was no difference in PTSD
      symptom profile between non-TBI and TBI groups. Our findings indicate that the
      presence of TBI is likely to influence the distribution of certain symptoms, but
      need not be a significant barrier to diagnosing ASD and PTSD.

PMID- 16281213
TI  - War zone stress without direct combat: the Australian naval experience of the
      Gulf War.
AB  - This study examines psychological stressors reported by Australian Navy Gulf War
      veterans in relation to the 1991 Gulf War and other military service. Using a 44
      item questionnaire, veterans reported few direct-combat encounters during the
      Gulf War; however, they reported many other stressful experiences, including fear
      of death and perceived threat of attack, more frequently in relation to the Gulf
      War than other military service. Reporting of stressful experiences was
      associated with younger age, lower rank, and deployment at the height of the
      conflict. These experiences may partly explain increased rates of psychological
      disorders previously demonstrated in this Navy veteran population. Findings
      highlight the importance of documenting war experiences in close proximity to
      deployment, and developing war exposure instruments which include naval
      activities and which reflect stressors other than those related to direct combat.

PMID- 16281214
TI  - Effects of brief eclectic psychotherapy in patients with posttraumatic stress
      disorder: randomized clinical trial.
AB  - Brief Eclectic Psychotherapy (BEP) is a manualized psychotherapy for
      posttraumatic stress disorder (PTSD) which has proven effective for police
      officers. This article reports on a randomized clinical trial using BEP to treat
      other types of PTSD patients recruited from an outpatient clinic. Twenty-four
      patients were randomly assigned to a treatment or a waitlist group. Assessment of
      PTSD was made before and after the treatment period (4 months). No significant
      differences between the groups were observed at pretest. By posttest, BEP had
      effectively reduced PTSD as well as general anxiety symptoms in the treated group
      of outpatients as compared to the waitlist group.

PMID- 16281215
TI  - Traumatic Exposure Severity Scale (TESS): a measure of exposure to major
      disasters.
AB  - The debate about the role of the intensity of the stressor has occupied a central
      focus in posttraumatic stress disorder literature. There is currently a paucity
      of instruments with established psychometric properties measuring severity of
      trauma exposure in disaster survivors. The Traumatic Exposure Severity Scale was
      developed specifically to assess dimensions of exposure to an earthquake disaster
      in adults. Its 24 items assess a wide range of stressors organized into five
      subscales, derived from factor analyses: Resource Loss, Damage to Home and Goods,
      Personal Harm, Concern for Significant Others, and Exposure to the Grotesque. The
      scale provides both Occurrence and Distress scores. It has good internal
      reliability and validity. The instrument correlates significantly, but
      moderately, with a number of traumatic stress measures and the Beck Depression
      Index.

PMID- 16281216
TI  - Is dissociation a multidimensional construct? Data from the Multiscale
      Dissociation Inventory.
AB  - The dimensionality of dissociation was examined in a combined sample of 1,326
      general population, clinical, and university participants who completed the
      Multiscale Dissociation Inventory (MDI). Principal components analysis identified
      five moderately intercorrelated factors (mean r = .39): Disengagement, Identity
      Dissociation, Emotional Constriction, Memory Disturbance, and
      Depersonalization/Derealization. Differential relationships were found between
      individual MDI factors and demographics, trauma history, clinical status,
      posttraumatic stress, and scores on other dissociation measures. Surprisingly,
      after controlling for sex and age, trauma exposure accounted for only 3 to 7% of
      the variance in MDI factors. The notion of dissociation as a general trait was
      not supported. Instead, dissociation may represent a variety of
      phenomenologically distinct and only moderately related symptom clusters whose
      ultimate commonality is more theoretical than empirical.

PMID- 16281217
TI  - An investigation of retrieval inhibition in acute stress disorder.
AB  - Acute stress disorder is characterized by dissociative responses that are
      theorized to result in deficient encoding and retrieval of trauma-related
      material. This study examined retrieval inhibition using the list method of the
      directed forgetting paradigm in traumatized individuals with acute stress
      disorder (ASD; n = 14), no ASD (n = 14), and a nontraumatized control group (n =
      15). Participants were presented with a list of intermixed positive, neutral, and
      trauma-related words. Instructions to forget that list and instead remember a
      second list were then given, and a new list presented. ASD participants exhibited
      poorer recall of to-be-forgotten trauma words than the non-ASD and control
      groups. The ASD group also demonstrated deficient recognition of to-be-remembered
      and to-be-forgotten positive words. Severity of acute posttraumatic stress
      response was associated with retrieval impairments. The cumulative findings
      suggest that ASD is associated with impoverished memory for trauma-related and
      positive material.

PMID- 16281218
TI  - An experimental examination of emotional experience, expression, and disclosure
      in women reporting a history of childhood sexual abuse.
AB  - Researchers have suggested that childhood sexual abuse (CSA) is a distal risk
      factor for the development of emotion regulation difficulties in adulthood. The
      present study examined 20 females with and without a history of CSA on the
      dimensions of subjective emotional experience (positive and negative activation),
      facial expressivity, and disclosure (positive and negative emotion words) in
      response to positively and negatively valenced film stimuli. The CSA group
      reported experiencing reduced positive activation while no group differences were
      found for negative activation. The CSA group disclosed fewer negative emotion
      words to express their experience and exhibited a trend towards less facial
      expressivity. The results are interpreted within the context of CSA survivors'
      emotional responding difficulties, and their implications are discussed.

PMID- 16281219
TI  - Impact of childhood traumatic events, trauma-related guilt, and avoidant coping
      strategies on PTSD symptoms in female survivors of domestic violence.
AB  - This investigation utilized path analyses to examine the direct and indirect
      effects of experiences of potentially traumatic events in childhood, trauma
      related guilt, and the use of avoidant coping strategies on level of PTSD
      symptomatology among a sample of female survivors of domestic violence. The
      results of this investigation indicated that individuals with more extensive
      histories of potentially traumatic events in childhood were more likely to report
      the experience of trauma-related guilt after exposure to domestic violence
      victimization in adulthood. Further, the path model indicated that experiencing
      trauma-related guilt was associated with greater use of avoidant coping
      strategies. Trauma-related guilt was related to increased PTSD symptomatology
      both directly and indirectly through the use of avoidant coping strategies. These
      findings highlight the importance of attending to guilt-based affective and
      cognitive reactions, maladaptive coping strategies, and the association between
      these constructs when treating survivors of relationship violence with multiple
      exposures to potentially traumatic events.

PMID- 16281220
TI  - Posttraumatic symptoms and self-dysfunction as consequences and predictors of
      sexual revictimization.
AB  - Posttraumatic symptomatology (PTS) and self-dysfunction (SD) were examined as
      correlates and predictors of sexual revictimization in a prospective study of 339
      college women. Both PTS and SD were associated with a history of child and adult
      sexual victimization. Compared to a history of child victimization, a history of
      adult victimization was associated with greater self-dysfunction. Both PTS and SD
      predicted revictimization during the study; however, self-dysfunction also
      predicted victimization in the absence of prior victimization. In a multivariate
      model, PTS did not directly predict victimization during the study, although SD
      mediated the relationship between PTS and victimization. Sexual victimization
      (child or adult) prior to the study predicted PTS, which predicted SD, which
      predicted victimization during the study. Findings suggest that prior child and
      adult victimization are directly related to later sexual victimization, and are
      indirectly related to later sexual victimization via the impact of PTS on SD.

PMID- 16281222
TI  - Interventions for survivors of the tsunami disaster: report from Sri Lanka.

PMID- 16281221
TI  - Facial recognition performance of female inmates as a result of sexual assault
      history.
AB  - This study examined the effect of sexual assault history on facial recognition
      performance. Gender of facial stimuli and posttraumatic stress disorder (PTSD)
      symptoms also were expected to influence performance. Fifty-six female inmates
      completed an interview and the Wechsler Memory Scale-Third Edition Faces I and
      Faces II subtests (Wechsler, 1997). Women with a sexual assault exhibited better
      immediate and delayed facial recognition skills than those with no assault
      history. There were no differences in performance based on the gender of faces or
      PTSD diagnosis. Immediate facial recognition was correlated with report of PTSD
      symptoms. Findings provide greater insight into women's reactions to, and the
      uniqueness of, the trauma of sexual victimization.

PMID- 16281224
TI  - Deployment stressors, gender, and mental health outcomes among Gulf War I
      veterans.
AB  - Findings indicate that war-zone exposure has negative implications for the
      postdeployment adjustment of veterans; however, most studies have relied on
      limited conceptualizations of war-zone exposure and focused on male samples. In
      this study, an array of deployment stressors that were content valid for both
      female and male Gulf War I military personnel was examined to elucidate gender
      differences in war-zone exposure and identify gender-based differential
      associations between stressors and mental health outcomes. While women and men
      were exposed to both mission-related and interpersonal stressors and both
      stressor categories were associated with mental health outcomes, women reported
      more interpersonal stressors and these stressors generally had a stronger impact
      on women's than on men's mental health. Exceptions are described, and
      implications are discussed.

PMID- 16281225
TI  - Disparities in mental health treatment following the World Trade Center Disaster:
      implications for mental health care and health services research.
AB  - To assess disparities in mental health treatment in New York City (NYC) after the
      World Trade Center Disaster (WTCD) reported previously related to care access, we
      conducted analyses among a cross-sectional survey of adults who had posttraumatic
      stress disorder (PTSD) or major depression (N = 473) one year after the event.
      The dependent variables examined were use of mental health services, in general,
      and use of mental health services related to the WTCD. Similar dependent
      variables were developed for medication usage. Although a number of bivariate
      results were statistically significant for postdisaster mental health visits, in
      a multivariate logistic regression model, only WTCD exposure remained
      significant. For service utilization related to the WTCD, the multivariate
      results indicated that African Americans were less likely to have had these
      visits compared to Whites, while those with a regular doctor, who had greater
      exposure to WTCD events, and those who had a perievent panic attack were more
      likely to have had such visits. In terms of medication use, multivariate results
      suggested that African Americans were less likely to use postdisaster
      medications, whereas persons 45 + years old and those with a regular doctor, were
      more likely to use them. For WTCD-related medication use, multivariate models
      indicated that African Americans were less likely to use medications, relative to
      Whites, while those between 45 and 64 years old, those with a regular doctor,
      those exposed to more WTCD events, and those who had a perievent panic attack,
      were more likely to have taken medications related to the disaster. The primary
      reason respondents gave for not seeking treatment (55% of subsample) was that
      they did not believe that they had a problem (73%). Other reasons were that they
      wanted to solve the problem on their own (5%), had problems accessing services
      (6%), had financial problems (4%), or had a fear of treatment (4%). Despite the
      availability of free mental health services offered in a supportive and
      potentially less stigmatizing environment post disaster, there still appeared to
      be barriers to receiving postdisaster services among those presumably in need of
      care.

PMID- 16281227
TI  - Patterns of treatment response in chronic posttraumatic stress disorder: an
      application of latent growth mixture modeling.
AB  - This study attempts to differentiate groups of individuals who exhibit different
      patterns of recovery following treatment for chronic posttraumatic stress
      disorder (PTSD) and describes these groups in terms of relevant characteristics
      at program intake. A sample of 2,219 Vietnam veterans who had completed a 12-week
      treatment program was followed up at 6, 12, and 24 months post admission using
      self-report measures. With change in PTSD symptoms over time as the focus, latent
      growth mixture modeling was used to assign individual veterans to subgroups. A
      three-group solution provided the best account of the data. Two groups showed
      moderate and consistent improvement over time although the larger group (n =
      1,380) began treatment with more PTSD symptoms and improved more quickly over
      time. The smallest group (n = 87) showed a substantially different trajectory,
      with almost no net change in symptom levels over the 24-month period. The groups
      also varied significantly in terms of their characteristics, with symptom
      severity and improvements over time reflecting greater comorbidity and younger
      age. The results have both research and clinical implications.

PMID- 16281226
TI  - Disaster-related posttraumatic stress symptoms and sustained attention:
      evaluation of depressive symptomatology and sleep disturbances as mediators.
AB  - Research about attentional functioning following trauma has almost exclusively
      been performed in patient populations with combat-related posttraumatic stress
      disorder (PTSD). In this study the relationship between sustained attention and
      PTSD symptoms was examined in a community sample of survivors of a major disaster
      using the Paced Auditory Serial Addition Task (PASAT) and the Self-Rating Scale
      for PTSD (SRS-PTSD) 2-3 years postdisaster. Analyses revealed low but significant
      partial correlations between PTSD symptoms and the least difficult subtests,
      ruling out the effects of age, education, depressive symptomatology, and sleep
      disturbances. These results demonstrate that PTSD symptoms link to attentional
      dysfunction 2-3 years postdisaster.

PMID- 16281228
TI  - Co-occurrence of posttraumatic stress disorder with positive psychotic symptoms
      in a nationally representative sample.
AB  - The association between posttraumatic stress disorder (PTSD) and positive
      psychotic symptoms was examined in the National Comorbidity Survey (N = 5,877).
      The Composite International Diagnostic Interview (CIDI) was used to make DSM-III
      R (Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised;
      American Psychiatric Association, 1987) diagnoses. Posttraumatic stress disorder
      was found to be associated with an increased likelihood of endorsing one or more
      psychotic symptoms after adjusting for sociodemographics, psychiatric and medical
      comorbidity (odds ratios (OR) = 1.83; 95% confidence interval (CI): 1.43-2.45; p
      < .001). The co-occurrence of PTSD with psychotic symptoms was marked by greater
      levels of severity (higher total number of PTSD symptoms, greater levels of
      comorbidity, and high distress) compared with PTSD alone. This is the first
      population-based study to investigate PTSD in relation to endorsement of positive
      psychotic symptoms, and a strong association was obtained.

PMID- 16281229
TI  - Prevalence and denial of sexual abuse in a male psychiatric inpatient population.
AB  - While the link between sexual abuse and psychiatric morbidity is well
      established, there are only a few studies that have investigated the prevalence
      of sexual abuse in male psychiatric populations and these studies have typically
      employed designs that ignore methodological issues specific to male sexual abuse.
      The present study aims to contribute to this research using as methodologically
      sound approach as possible. Seventy-four male inpatients were interviewed using a
      questionnaire (J. N. Briere, 1992) about childhood sexual experiences.
      Approximately one third reported incidents that met this study's criteria for
      sexual abuse. Many of these men did not label such experiences as "sexual abuse."
      The results suggest that mental health professionals need to be aware that many
      of their male patients may have a history of sexual abuse and that potential
      minimization or denial of it is a barrier to disclosure.

PMID- 16281230
TI  - Personal resources, coping self-efficacy, and quake exposure as predictors of
      psychological distress following the 1999 earthquake in Turkey.
AB  - This study examined the predictive power of personal resources (i.e., self
      esteem, optimism, and perceived control), severity of earthquake experience
      (i.e., material and human loss and perceived threat), and coping self-efficacy
      (CSE) on general distress, intrusion, and avoidance symptoms among the survivors
      of the 1999 Marmara earthquake in Turkey. Specifically, we expected that CSE
      would mediate the links between personal resources, severity of earthquake
      experience, and distress. Survivors (N = 336) filled out various measures of
      earthquake exposure, personal resources, CSE, and distress. Results of the path
      analyses indicated that personal resources, earthquake experiences, CSE, and
      gender have direct effects on intrusion and general distress. Personal resources
      had also an indirect effect on general distress mediated by CSE. Findings were
      discussed considering the implications for conservation of resources model and
      social cognitive theory as well as for interventions following natural disasters.

PMID- 16281231
TI  - Sleep quality in complicated grief.
AB  - The aim of the present study was to evaluate severity of sleep disturbances in a
      group of 105 individuals presenting with complicated grief (CG) accompanied or
      not by comorbid depression and/or posttraumatic stress disorder (PTSD). A sample
      of 105 adults meeting criteria for CG was included in this study. All completed
      the Pittsburgh Sleep Quality Index (PSQI). The total sample presented a mean
      global PSQI score of 9.44, indicating overall poor sleep quality. Comorbid
      depression, but not PTSD, further worsened sleep quality. Further studies are
      required to investigate the potential role of poor sleep quality as a modifiable
      risk factor of complicated grief response.

PMID- 16281232
TI  - Mismatch of posttraumatic stress disorder (PTSD) symptoms and DSM-IV symptom
      clusters in a cancer sample: exploratory factor analysis of the PTSD Checklist
      Civilian Version.
AB  - The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM
      IV; American Psychiatric Association, 1994a) conceptualization of posttraumatic
      stress disorder (PTSD) includes three symptom clusters: reexperiencing,
      avoidance/numbing, and arousal. The PTSD Checklist-Civilian Version (PCL-C)
      corresponds to the DSM-IV PTSD symptoms. In the current study, we conducted
      exploratory factor analysis (EFA) of the PCL-C with two aims: (a) to examine
      whether the PCL-C evidenced the three-factor solution implied by the DSM-IV
      symptom clusters, and (b) to identify a factor solution for the PCL-C in a cancer
      sample. Women (N = 148) with Stage II or III breast cancer completed the PCL-C
      after completion of cancer treatment. We extracted two-, three-, four-, and five
      factor solutions using EFA. Our data did not support the DSM-IV PTSD symptom
      clusters. Instead, EFA identified a four-factor solution including
      reexperiencing, avoidance, numbing, and arousal factors. Four symptom items,
      which may be confounded with illness and cancer treatment-related symptoms,
      exhibited poor factor loadings. Using these symptom items in cancer samples may
      lead to overdiagnosis of PTSD and inflated rates of PTSD symptoms.

PMID- 16281233
TI  - A taxometric investigation of dissociation in Vietnam veterans.
AB  - There is long-standing debate about whether elevated dissociative symptoms are
      common in posttraumatic stress disorder (PTSD) or whether there is a distinct
      subtype of cases with elevated dissociation. The current investigation examined
      the latent structure of dissociative symptoms in a sample of 316 male, trauma
      exposed Vietnam veterans, 76 of whom were diagnosed with current PTSD. Three
      taxometric procedures (MAMBAC, MAXEIG, and MAXCOV) were performed on three
      indicator sets drawn from the Dissociative Experiences Scale. Taxometric analyses
      consistently revealed a taxon (subtype) of highly dissociative individuals. The
      taxon members had significantly more severe posttraumatic symptoms and were more
      often diagnosed with current PTSD than were non-taxon members. Among participants
      with a current PTSD diagnoses, only 32% belonged to the dissociative taxon,
      suggesting that there is a subtype of severe PTSD with elevated dissociation.

PMID- 16281234
TI  - Psychometric properties of the PTSD Checklist with older primary care patients.
AB  - In this article the authors evaluated the posttraumatic stress disorder (PTSD)
      Checklist's (PCL) psychometric properties in 142 older adult primary care
      patients screened for several psychiatric disorders. Several established PCL
      scoring rules were assessed. Receiver operating characteristic analyses revealed
      a PCL score of 37 achieving optimal sensitivity and specificity, when compared to
      the PCL's algorithm-derived PTSD diagnosis (based on whether at least one
      reexperiencing, three avoidance/numbing, and two hyperarousal symptoms were
      endorsed with a rating of 3 or higher, indicating at least moderate severity).
      Among depressed, anxious, and substance abusing older adults, the PCL
      demonstrated adequate internal consistency. It also revealed similar convergence
      with the Center for Epidemiological Studies-Depression scale, found in previous
      research. Implications for using the PTSD Checklist with community-dwelling older
      adults in primary care are discussed.

PMID- 16281236
TI  - Editorial comments: Complex developmental trauma.

PMID- 16281237
TI  - Disorders of extreme stress: The empirical foundation of a complex adaptation to
      trauma.
AB  - Children and adults exposed to chronic interpersonal trauma consistently
      demonstrate psychological disturbances that are not captured in the posttraumatic
      stress disorder (PTSD) diagnosis. The DSM-IV (American Psychiatric Association,
      1994) Field Trial studied 400 treatment-seeking traumatized individuals and 128
      community residents and found that victims of prolonged interpersonal trauma,
      particularly trauma early in the life cycle, had a high incidence of problems
      with (a) regulation of affect and impulses, (b) memory and attention, (c) self
      perception, (d) interpersonal relations, (e) somatization, and (f) systems of
      meaning. This raises important issues about the categorical versus the
      dimensional nature of posttraumatic stress, as well as the issue of comorbidity
      in PTSD. These data invite further exploration of what constitutes effective
      treatment of the full spectrum of posttraumatic psychopathology.

PMID- 16281238
TI  - Phenomenology and psychological assessment of complex posttraumatic states.
AB  - The authors offer a framework for the assessment of psychological responses
      associated with exposure to early onset, multiple, or extended traumatic
      stressors. Six prominent and overlapping symptoms clusters are described: altered
      self-capacities, cognitive symptoms, mood disturbance, overdeveloped avoidance
      responses, somatoform distress, and posttraumatic stress. A strategy for the
      structured, psychometrically valid assessment of these outcomes is introduced,
      and specific recommendations for use of various generic and trauma-specific child
      and adult measures are provided. Implications of trauma assessment for treatment
      planning are discussed.

PMID- 16281239
TI  - Dissociation: An insufficiently recognized major feature of complex posttraumatic
      stress disorder.
AB  - The role of dissociation in (complex) posttraumatic stress disorder (PTSD) has
      been insufficiently recognized for at least two reasons: the view that
      dissociation is a peripheral, not a central feature of PTSD, and existing
      confusion regarding the nature of dissociation. In this conceptual article, the
      authors address both issues by postulating that traumatization essentially
      involves some degree of division or dissociation of psychobiological systems that
      constitute personality. One or more dissociative parts of the personality avoid
      traumatic memories and perform functions in daily life, while one or more other
      parts remain fixated in traumatic experiences and defensive actions. Dissociative
      parts manifest in negative and positive dissociative symptoms that should be
      distinguished from alterations of consciousness. Complex PTSD involves a more
      complex structural dissociation than simple PTSD.

PMID- 16281240
TI  - Posttraumatic stress disorder treatment outcome research: The study of
      unrepresentative samples?
AB  - The authors review sample composition and enrollment data for 34 studies cited in
      the International Society for Traumatic Stress Studies (ISTSS) 2000 Practice
      Guidelines as meeting the Level A U.S. Agency for Health Care Policy and Research
      (AHCPR) classification for treatment of adult posttraumatic stress disorder
      (PTSD), and compare data from more recent research. Findings reveal that many
      published reports omitted vital data including exclusion criteria and rates,
      demographics, and trauma exposure history. Moreover, severe comorbid
      psychopathology, a common feature of treatment-seeking individuals with PTSD,
      emerged as the predominant reason for exclusion across studies. Subsequently
      published studies exhibited improved reporting of sample characteristics and
      demonstrated comparable outcomes despite inclusion of more diverse trauma
      exposure samples. Findings indicate the need for future efficacy research to
      adopt more comprehensive reporting requirements and to test the applicability of
      validated treatments to individuals suffering from as yet unstudied combinations
      of PTSD and prevalent comorbid disorders.

PMID- 16281241
TI  - Treatment of complex posttraumatic self-dysregulation.
AB  - The authors describe a three-phase sequential integrative model for the
      psychotherapy of complex posttraumatic self-dysregulation: Phase 1 (alliance
      formation and stabilization), Phase 2 (trauma processing), and Phase 3
      (functional reintegration). The technical precautions designed to maximize
      safety, trauma processing, and reintegration regardless of the specific treatment
      approach are discussed. Existing and emerging treatment models that address
      posttraumatic dysregulation of consciousness, bodily functioning, emotion, and
      interpersonal attachments are also described. The authors conclude with
      suggestions for further clinical innovation and research evaluation of
      therapeutic models that can enhance the treatment of PTSD by addressing complex
      posttraumatic self-dysregulation.

PMID- 16281242
TI  - Clinical applications of the attachment framework: Relational treatment of
      complex trauma.
AB  - The self and attachment difficulties associated with chronic childhood abuse and
      other forms of pervasive trauma must be understood and addressed in the context
      of the therapeutic relationship for healing to extend beyond resolution of
      traditional psychiatric symptoms and skill deficits. The authors integrate
      contemporary research and theory about attachment and complex developmental
      trauma, including dissociation, and apply it to psychotherapy of complex trauma,
      especially as this research and theory inform the therapeutic relationship.
      Relevant literature on complex trauma and attachment is integrated with
      contemporary trauma theory as the background for discussing relational issues
      that commonly arise in this treatment, highlighting common challenges such as
      forming a therapeutic alliance, managing frame and boundaries, and working with
      dissociation and reenactments.

PMID- 16281243
TI  - Participant reactions to survey research in the general population after
      terrorist attacks.
AB  - There remains concern that survey research after a disaster can precipitate or
      exacerbate distress among study participants. The authors surveyed 5,774 persons
      in three random-digit-dial telephone surveys of the general population of New
      York City conducted 1-2 months, 4-5 months, and 6-9 months after the terrorist
      attack on September 11, 2001. Overall, 746 (12.9%) people who finished the
      surveys said that the survey questions were upsetting but only 57 (1.0% overall)
      were still upset at the end of the interview, and 19 (0.3%) wanted assistance
      from a counselor. Ten persons who did not finish the survey also received
      counselor assistance. Persons with mental health symptoms were more likely to
      find the survey questions emotionally upsetting as were participants who lacked
      salutary resources, including health insurance and a regular health care
      provider. Although relatively few of those interviewed found the survey
      assessment disturbing, the presence of a small number of respondents who wanted
      mental health assistance suggests the need for a mental health backup system for
      research conducted soon after exposure to large-scale traumatic events.

PMID- 16281244
TI  - The double-barreled burden of child abuse and current stressful circumstances on
      adult women: The kindling effect of early traumatic experience.
AB  - Child sexual abuse and child physical abuse were compared to assess how these
      experiences might both positively predict and sensitize women to the effects of
      current stress exposure, assessed in terms of psychosocial resource loss (e.g.,
      personal and interpersonal resources). Resource loss was in turn, hypothesized to
      increase later depressive mood and posttraumatic stress disorder severity.
      Participants were 176 low-income women (58% African American, 38% European
      American), interviewed twice over 6 months. Child sexual abuse predicted
      increases in resource loss, which then predicted posttraumatic stress disorder
      and depressive mood. Women who reported higher levels of child physical abuse
      were more negatively impacted by resource loss than those who reported lower
      child physical abuse. Results suggest that child abuse results in both greater
      stress exposure later and greater vulnerability to that exposure.

PMID- 16281245
TI  - Psychological consequences of the Bam earthquake on professional and
      nonprofessional helpers.
AB  - This study compared the psychological status of rescue personnel who had formal
      training (Red Crescent workers, i.e., Red Cross workers, and firefighters) with
      university student volunteers who had no formal training in handling traumatic
      situations in the Bam earthquake. One hundred student volunteers, 18 Red Crescent
      workers, and 36 firefighters participated in this study. Participants completed
      the Civilian Mississippi Scale, the General Health Questionnaire (GHQ-28), and
      the Anxiety Sensitivity Index. Helpers without formal training showed higher
      scores on posttraumatic stress disorder (PTSD) and GHQ subscales compared to
      trained rescue personnel. In addition, a significant number of volunteers without
      formal training met criteria for a possible PTSD diagnosis by scoring above the
      cut-off point for the Mississippi scale. Those who had higher scores on the
      Anxiety Sensitivity Index showed greater adverse psychological effects.

PMID- 16281247
TI  - Religiosity and secondary traumatic stress in Israeli-Jewish body handlers.
AB  - This study investigated the relationship between religiosity and levels of
      secondary traumatic stress in Israeli-Jewish body handlers. The Impact of Event
      Scale (IES), the General Health Questionnaire, 12 Items (GHQ-12), and a prior
      exposure severity tool were used to assess secondary traumatic stress symptoms in
      63 ultraorthodox male body handlers as they compared to 86 secular forensic
      identification technicians from the Israeli police. Excluding possible
      confounders of age and number of years at the job, there was no significant
      difference between the religious and nonreligious groups on the intrusion and
      avoidance scores, whereas the GHQ-12 scores were significantly higher among the
      religious group. Religiosity did not seem to have a salutary effect on secondary
      traumatic stress in this cohort.

PMID- 16281246
TI  - Identification and posttraumatic stress disorder symptoms in rescue workers in
      the Marmara, Turkey, earthquake.
AB  - After the 1999 Marmara Turkey earthquake, 434 volunteer rescue workers and 154
      soldiers who were control subjects completed the Questionnaire for Identification
      with Deceased Victims and the Impact of Event Scale-Revised (IES-R).
      Identification with the Deceased as Oneself, Identification with the Deceased as
      a Friend, Identification with the Deceased as a Family Member, and IES-R
      Intrusion, Avoidance, and Hyperarousal subscale scores were significantly higher
      in rescue workers. Identification-Self, Identification-Friend, and Identification
      Family correlated with the IES-R subscale and total scores. The set of
      identification variables was significantly associated with group membership
      before, but not after, IES-R scores were controlled. Findings suggest that
      identification with deceased victims, not rescue work per se, is the risk factor
      of concern for posttraumatic stress disorder in rescue workers.

PMID- 16281248
TI  - Risk and resilience in canine search and rescue handlers after 9/11.
AB  - Research has suggested that rescue workers are at increased risk for
      psychological distress. To determine whether 9/11 deployment was a significant
      risk factor for canine search and rescue handlers, 82 deployed handlers were
      compared to 32 nondeployed handlers on measures of posttraumatic stress disorder
      (PTSD), depression, anxiety, acute stress, and clinical diagnoses. Deployed
      handlers reported more PTSD and general psychological distress 6 months after
      9/11. Among deployed handlers, prior diagnoses and peritraumatic reactions were
      associated with psychological distress whereas social support and training were
      protective. Results suggest that more extensive screening and prophylactic
      interventions for individuals with a history of mental illness could be
      beneficial. Future research should examine identified risk/resilience factors
      prospectively, and training and intervention should be designed accordingly.

PMID- 16281249
TI  - Event-list construction and treatment of exposure data in research on political
      violence.
AB  - Event lists are commonly applied for measuring exposure to various kinds of
      potentially stressful and traumatizing life events. Before making general
      conclusions about the psychological effects of exposure to such events,
      problematic issues related to the use of event-list data need to be discussed and
      resolved. This article focuses on issues related to the construction and
      application of event lists for measuring exposure to political violence such as
      issues related to reliability, the applicability of the additive assumption,
      whether to weight event-list items, and the possible consequences of incomplete
      event lists. Alternative future approaches to these measurement issues are also
      discussed.

PMID- 16281250
TI  - Development and validation of a new instrument to assess lifetime trauma and
      victimization history.
AB  - This article describes a new easy-to-administer and understand, interview-based
      instrument that systematically and comprehensively assesses a person's Lifetime
      Trauma and Victimization History (LTVH). The LTVH inquires about 30 traumas and
      victimization experiences (including general traumas, physical assault/abuse,
      sexual assault/abuse, kidnapping/stalking, family/friend murdered or committed
      suicide, witnessed trauma to someone else, and crime victimizations) and age of
      onset, perpetrator, degree of danger and fear experienced, duration, and
      frequency of each experience. We present evidence of predictive validity of the
      LTVH as well as convergent and criterion validity for the child abuse items using
      information from individuals with documented histories of child abuse and neglect
      and matched comparisons (without documented histories of childhood
      victimization). The 896 individuals (mean age = 39.5 years) reported 11,850
      traumas or victimization experiences. The LTVH demonstrates good predictive,
      criterion-related, and convergent validity and a high level of agreement between
      earlier and current reports of certain types of traumas.

PMID- 16281251
TI  - Sexual revictimization among sexual minorities: A preliminary study.
AB  - The present study examined patterns of sexual assault and its psychological
      correlates among gay men, lesbians, and bisexual men and women (GLB). A community
      sample of 342 GLB individuals completed questionnaires assessing victimization
      history and psychological functioning. Nearly 63% of participants reported some
      form of sexual assault, and nearly 40% reported sexual revictimization, defined
      as contact or penetrative sexual assault reported in both childhood and
      adulthood. Gay men and bisexual men and women were more likely to report sexual
      revictimization than lesbians. Sexual victimization was associated with greater
      psychological distress, with sexually revictimized individuals reporting the
      highest levels of psychological symptomatology. The implications of these
      findings are discussed, and suggestions for future directions are offered.

PMID- 16281252
TI  - Which instruments are most commonly used to assess traumatic event exposure and
      posttraumatic effects?: A survey of traumatic stress professionals.
AB  - We report findings from a Web-based survey of the International Society for
      Traumatic Stress Studies' members (n = 227) regarding use of trauma exposure and
      posttraumatic assessment instruments. Across clinical and research settings, the
      most widely used tests included the Posttraumatic Stress Diagnostic Scale, Trauma
      Symptom Inventory, Life Events Checklist, Clinician-Administered Post-traumatic
      Stress Disorder (PTSD) Scale, PTSD Checklist, Impact of Event Scale-Revised, and
      Trauma Symptom Checklist for Children. Highest professional degree, time since
      degree award, and student status yielded no differences in extent of reported
      trauma assessment test use.

PMID- 16281253
TI  - Psychological impact of types of sexual trauma among college women.
AB  - Studies typically demonstrate that sexual victimization is associated with
      negative outcomes, yet they often fail to control for other trauma exposure and
      rarely address the impact of developmental level at the time of exposure or the
      type of sexual trauma experienced. The present study addresses these confounds by
      identifying groups of women with unique, nonoverlapping sexual trauma histories
      and examines the association between type of sexual trauma exposure and mental
      health impairment, social adjustment, and sexual functioning. This study compared
      five discrete groups of college-sophomore women based on self-identified trauma
      histories including no trauma, childhood sexual assault, childhood sexual abuse,
      adolescent sexual assault, and revictimization. Significant differences based on
      sexual trauma type were observed; individuals who experienced adolescent sexual
      assault or revictimization were at greatest risk for psychopathology, poor social
      adjustment, and risky sexual behaviors.

PMID- 16281254
TI  - Health costs following motor vehicle accidents: The role of posttraumatic stress
      disorder.
AB  - This pilot study examined whether posttraumatic stress disorder (PTSD) was
      associated with increased health costs following severe injury caused by motor
      vehicle accidents. Three groups of injury survivors were created from a larger
      sample--PTSD only, no-PTSD-low physical function, and no-PTSD--high physical
      function-and these groups were compared on health cost outcomes at 12 and 24
      months. The presence of PTSD was associated with increased total health costs for
      both Year 1 and Year 2. However, PTSD, per se, did not independently contribute
      to total health costs. This study suggests that ongoing physical health problems
      must be considered in order to accurately assess the unique contribution that
      PTSD makes to health costs in the physically injured population.

PMID- 16281255
TI  - Evaluation of premorbid personality factors and pre-event posttraumatic stress
      symptoms in the development of posttraumatic stress symptoms associated with a
      bus explosion in Israel.
AB  - This study examined the role played by indicators of premorbid personality in the
      development of posttraumatic stress symptoms (PTSS). The initial sample consisted
      of 185 undergraduate students who had coincidentally been evaluated for their
      PTSS levels 2 weeks prior to a terrorist explosion. A week after the explosion,
      the sample was assessed to determine the extent of actual exposure. Of the
      initial 185 students, 81 reported being exposed and thus constituted the final
      cohort. They were reevaluated at 1 month after the explosion. Both assessments
      included personality and PTSS evaluation. Data analyses revealed five positive
      predictors of PTSS levels: high pre-attack PTSS levels, personal exposure,
      significant other's exposure, indirect exposure, and high premorbid levels on the
      harm avoidance personality dimension.

PMID- 16281256
TI  - Emotional numbing in relation to stressful civilian experiences among college
      students.
AB  - Investigators have shown that hyperarousal is the best predictor of emotional
      numbing (EN), as compared with avoidance and reexperiencing. The aim of the
      present study was to extend this finding to the context of stressful civilian
      experiences among college students. Participants (N = 1,292) completed self
      report checklists of stressful civilian experiences and PTSD symptoms. The
      results of multiple regression analyses in two subsamples consistently indicated
      that both hyperarousal and avoidance were good predictors of EN. These findings
      suggest that avoidance may play a more important role in the relationship between
      hyperarousal and EN in college students.

PMID- 16281257
TI  - Multidimensional nature of posttraumatic growth in an Australian population.
AB  - Recent trauma literature has supported a philosophical shift from a pathogenic to
      a salutogenic paradigm in which the focus is on positive, as well as negative,
      posttrauma changes; however, empirical knowledge exploring the different domains
      of positive change or posttraumatic growth (PTG) is scarce. The present study
      investigated the multidimensionality of PTG in Australian undergraduate students
      (N = 219). Results indicated five factors for the Posttraumatic Growth Inventory,
      and moderate levels of PTG. Trauma severity was found to significantly predict
      PTG in addition to a positive correlation between PTG and negative posttrauma
      effects. While not negating negative effects of traumatic experiences, this area
      of traumatology research has important implications for redefining the "victims"
      of trauma as individuals capable of positive change rather than merely surviving.

PMID- 16281259
TI  - Population-based study of cancer among carriers of a constitutional structural
      chromosomal rearrangement.
AB  - We measured the occurrence of cancer in an unselected cohort of carriers of
      constitutional structural rearrangements in virtually complete nationwide
      registries for cancer and constitutional cytogenetic abnormalities. We identified
      4,816 carriers of a constitutional structural rearrangement in the Danish
      Cytogenetic Registry and searched for cancer diagnoses by linkage to the Danish
      Cancer Registry. There was no overall increased risk for cancer among carriers
      (standardized incidence ratio [SIR], 0.96; 95% confidence interval [CI], 0.84
      1.10), and no significant difference from that expected was found in balanced and
      unbalanced rearrangements or in any subtypes of rearrangements. We found
      significantly lower risks for carriers with rearrangements involving chromosome
      21 (SIR, 0.50; 95% CI, 0.22-0.99) and for paternally inherited rearrangements
      (SIR, 0.30; 95% CI, 0.06-0.88). Risk estimates for the observed type-specific
      cancers showed an increased risk for non-Hodgkin lymphoma (SIR, 2.11; 95% CI,
      1.09-3.69). However, subgroup analyses were not guided by study hypotheses, and
      our statistical evaluation of the data should be looked upon as exploratory. In
      addition, we found 12 constitutional structural rearrangements with a breakpoint
      potentially associated with a cancer-related gene. Potential new loci associated
      with type-specific cancers were suggested by the findings of families with more
      than one affected carrier and by the involvement of the same cytogenetic bands in
      unrelated carriers. Molecular mapping of these breakpoints might provide new
      insight into cancer predisposition.

PMID- 16281258
TI  - Proteomic analysis of rat laryngeal muscle following denervation.
AB  - Laryngeal muscle atrophy induced by nerve injury is a major factor contributing
      to the disabling symptoms associated with laryngeal paralysis. Alterations of
      global proteins in rat laryngeal muscle following denervation were, therefore,
      studied using proteomic techniques. Twenty-eight adult Sprague-Dawley rats were
      divided into normal control and denervated groups. The thyroarytenoid (TA) muscle
      was excised 60 days after right recurrent laryngeal nerve was resected. Protein
      separation and identification were preformed using 2-DE and MALDI-MS with
      database search. Forty-four proteins were found to have significant alteration in
      expression level after denervation. The majority of these proteins (57%), most of
      them associated with energy metabolism, cellular proliferation and
      differentiation, signal transduction and stress reaction, were decreased levels
      of expression in denervated TA muscle. The remaining 43% of the proteins, most of
      them involved with protein degradation, immunoreactivity, injury repair,
      contraction, and microtubular formation, were found to have increased levels of
      expression. The protein modification sites by phosphorylation were detected in
      22% of the identified proteins that presented multiple-spot patterns on 2-D gel.
      Significant changes in protein expression in denervated laryngeal muscle may
      provide potential therapeutic strategies for the treatment of laryngeal
      paralysis.

PMID- 16281260
TI  - Critically short telomeres in acute myeloid leukemia with loss or gain of parts
      of chromosomes.
AB  - Telomeres, nucleoprotein complexes at chromosome ends, protect chromosomes
      against end-to-end fusion. Previous in vitro studies in human fibroblast models
      indicated that telomere dysfunction results in chromosome instability. Loss of
      telomere function can result either from critical shortening of telomeric DNA or
      from loss of distinct telomere-capping proteins. It is less clear whether
      telomere dysfunction has an important role in human cancer development in vivo.
      Acute myeloid leukemia (AML) is a good model to study mechanisms that generate
      chromosome instability in human cancer development because distinct groups of AML
      are characterized either by aberrations that theoretically could result from
      telomere dysfunction (terminal deletions, gains/losses of chromosome parts,
      nonreciprocal translocations), or aberrations that are unlikely to result from
      telomere dysfunction (e.g., reciprocal translocations or inversions). Here we
      demonstrate that AML with multiple chromosome aberrations that theoretically
      could result from telomere dysfunction is invariably characterized by critically
      short telomeres. Short telomeres in this group are not associated with low
      telomerase activity or decreased expression of essential telomeric capping
      proteins TRF2 and POT1. In contrast, telomerase activity levels are significantly
      higher in AML with short telomeres. Notably, short telomeres in the presence of
      high telomerase may relate to significantly higher expression of TRF1, a negative
      regulator of telomere length. Our observations suggest that, consistent with
      previous in vitro fibroblast models, age-related critical telomere shortening may
      have a role in generating chromosome instability in human AML development.

PMID- 16281261
TI  - Chromosome 18 suppresses tumorigenic properties of human prostate cancer cells.
AB  - Although prostate cancer is still the most diagnosed cancer in men, most genes
      implicated in its progression are yet to be identified. Chromosome abnormalities
      have been detected in human prostate tumors, many of them associated with
      prostate cancer progression. Indeed, alterations (including deletions or
      amplifications) of more than 15 human chromosomes have been reported in prostate
      cancer. We hypothesized that transferring normal human chromosomes into human
      prostate cancer cells would interfere with their tumorigenic and/or metastatic
      properties. We used microcell-mediated chromosome transfer to introduce human
      chromosomes 10, 12, 17, and 18 into highly tumorigenic (PC-3M-Pro4) and highly
      metastatic (PC-3M-LN4) PC-3-derived cell lines. We tested the in vitro and in
      vivo properties of these hybrids. Introducing chromosome 18 into the PC-3M-LN4
      prostate cancer cell line greatly reduced its tumorigenic phenotype. We observed
      retarded growth in soft agar, decreased invasiveness through Matrigel, and
      delayed tumor growth into nude mice, both subcutaneously and orthotopically. This
      phenotype is associated with a marker in the 18q21 region. Combined with the loss
      of human chromosome 18 regions often seen in patients with advanced prostate
      cancer, our results show that chromosome 18 encodes one or more tumor-suppressor
      genes whose inactivation contributes to prostate cancer progression.

PMID- 16281263
TI  - Sonographically guided thoracentesis and rate of pneumothorax.
AB  - PURPOSE: To assess whether thoracenteses performed with sonographic guidance are
      associated with a lower rater of pneumothorax and tube thoracostomy than those
      performed without sonographic guidance. METHODS: We reviewed the medical records
      of 523 subjects undergoing their initial diagnostic thoracentesis at our
      institution from July 1, 2001, to June 30, 2002. We excluded 73 subjects in whom
      no chest imaging had been performed within 5 days of thoracentesis or who had pre
      existing chronic hydropneumothorax. RESULTS: Of the 450 thoracenteses performed,
      305 (67.8%) were performed with sonographic guidance and 145 (32.2%) were
      performed without. On postthoracentesis imaging in all subjects, 30
      pneumothoraces (6.7%) were found (23 inpatients, 7 out-patients). Eight patients
      required a tube thoracostomy for their pneumothorax. Pneumothorax occurred in 15
      of 305 procedures (4.9%) performed with sonographic guidance and 15 of 145
      procedures (10.3%) performed without (p < 0.05). Tube thoracostomy was performed
      in 0.7% of patients whose thoracentesis was performed with sonographic guidance
      and in 4.1% in those that were not (p < 0.05). We found no correlation between
      pneumothorax after thoracentesis and age, inpatient status, loculation of
      effusion, or volume of pleural fluid removed. CONCLUSIONS: The routine use of
      sonography during diagnostic thoracentesis is associated with a reduced rate of
      pneumothorax and tube thoracostomy.

PMID- 16281264
TI  - Foot pedal-activated injector for contrast-enhanced sonography.
AB  - We assessed the feasibility and convenience of an injector that is electrically
      activated by a foot pedal for contrast-enhanced sonography. Thirty-seven patients
      with liver lesions underwent contrast-enhanced sonography using an injector that
      is activated by a foot pedal. The contrast agent was injected by pressing the
      foot pedal. All the studies were successfully performed without complications.
      The device enables the sonologist to keep the probe stationary during the
      injection and avoids the need for additional personnel. Pedal activated injection
      is a safe, useful, and convenient method of contrast-enhanced sonography.

PMID- 16281265
TI  - Sonographic appearance of a carcinoma developed in ectopic axillary breast
      tissue.
AB  - Primary breast cancer of ectopic axillary breast tissue is almost never diagnosed
      preoperatively. When not accompanied by nipple-areolar complex, the mass is often
      believed to be a lipoma, an enlarged lymph node, or a skin lesion such as a
      sebaceous cyst or hydradenitis suppurativa. When an axillary mass is found, a
      percutaneous needle biopsy is mandatory to rule out the diagnosis of cancer in
      ectopic breast tissue. We describe the sonographic findings of a case of ductal
      carcinoma in axillary ectopic breast tissue.

PMID- 16281266
TI  - Sonographic appearance of a tear of the lateral internal oblique muscle resulting
      from cough.
AB  - During forced respiratory movement such as coughing, complications can occur,
      including abdominal muscle rupture. We report a case of spontaneous tear of the
      internal oblique muscle resulting from violent cough diagnosed by sonography. The
      physiology of cough and the possible pathophysiologic mechanism of this case is
      discussed.

PMID- 16281267
TI  - Color Doppler twinkling artifact in a calcified liver mass.
AB  - Twinkling artifact in color Doppler imaging is related both to the presence of a
      strongly reflective structure and to the scanner's settings. This artifact has
      been described in association with calculi and various foreign bodies, but to our
      knowledge it has not been reported in a hepatic mass. If a calcified hepatic mass
      is examined with color Doppler Mapping without using spectral Doppler analysis,
      misinterpreted as real blood flow and lead to the erroneous of hypervascular
      mass.

PMID- 16281268
TI  - Sonographic measurement of the thickness of subcutaneous tissues in nonalcoholic
      fatty liver disease versus other chronic liver diseases.
AB  - PURPOSE: To measure an average subcutaneous tissue thickness in nonalcoholic
      fatty liver disease (NAFLD) and other liver diseases using bedside sonography and
      make comparisons of thickness between groups. The study also addressed whether a
      cut-off subcutaneous tissue thickness exists below which NAFLD is unlikely.
      METHODS: Sonograph was performed on 113 consecutive patients with chronic liver
      disease. Diagnosis was derived from serological data combined with liver biopsy
      in all cases. Distance was measured between the skin and the liver surface and
      was labeled the subcutaneous tissue thickness. RESULTS: Of the 113 patients, 16
      were diagnosed with NAFLD, 56 were diagnosed with chronic hepatitis C, 17 were
      diagnosed with autoimmune liver disease, and 24 had miscellaneous diagnoses
      (hepatitis B, hemochromatosis, granulomatous hepatitis, and cryptogenic
      hepatitis). The subcutaneous tissue thickness was 25.6 mm +/- 5.6 mm in NAFLD
      versus 19.5 mm +/- 5.2 in the non-NAFLD patients (p < 0.001). The subcutaneous
      tissue thickness of the HCV group was 20.2 mm +/- 4.8, and although it was not
      different than all other patients, it was different from the NAFLD patients (p <
      0.01). Fifteen out of sixteen of the NAFLD patients had a greater than average
      subcutaneous tissue thickness (20 mm). CONCLUSIONS: A sonographically measured
      subcutaneous tissue thickness of less than 20 mm makes the diagnosis of NAFLD
      unlikely.

PMID- 16281269
TI  - Tubular ectasia of the epididymis: a sign of postvasectomy status.
AB  - PURPOSE: To find out if "tubular ectasia of the epididymis" is suggestive of
      postvasectomy status. METHODS: Tubular ectasia of the epididymis is defined as
      enlargement of the epididymis with multiple interfaces (i.e., a speckled
      appearance). We found 24 cases exhibiting tubular ectasia of the epididymis over
      a period of six years. We reviewed the sonographic findings of tubular ectasia of
      the epididymis and evaluated the prevalence of associated findings. RESULTS: In
      24 patients with tubular ectasia of the epididymis, 16 cases were bilateral, five
      were right-sided, and three were left-sided. Twenty-one patients had history of
      vasectomy, of the three remaining cases, 1 had history of inguinal hernia repair,
      one had prostatitis, and one had undetermined etiology. Associated abnormalities
      included dilated vas deferens (n = 4), tubular ectasia of the testis (n = 2),
      large spermatoceles (n = 6), hydrocele (n = 3), and varicocele (n = 4). In 2
      cases, spermatic granulomas were suspected. CONCLUSION: Tubular ectasia of the
      epididymis is suggestive of postvasectomy epididymis. This sonographic feature is
      helpful in evaluating a patient with scrotal discomfort. However, this sign can
      also be associated with other causes of vas obstruction.

PMID- 16281270
TI  - Patients' tolerance and early complications of transrectal sonographically guided
      prostate biopsy: prospective study of 300 patients.
AB  - PURPOSE: To determine the degree of pain and discomfort associated with
      transrectal sonography (TRS)-guided biopsy of the prostate and to analyze the
      complications associated with this procedure. METHODS: Three hundred men referred
      as part of an investigation to exclude prostate cancer were studied. The reasons
      for referral were suspected prostate cancer due to increased serum prostate
      specific antigen level (>4 ng/ml), the finding of a palpable nodule or greater
      firmness of one prostatic lobe than the other on digital rectal examination, or
      the finding of a suspicious area of neoplasm of the prostate on TRS biopsy. All
      TRS-guided biopsies were performed as outpatient procedures without anesthesia.
      Ciprofloxacin prophylaxis was used in all patients before biopsy. Tolerance of
      the procedure was recorded immediately after the examination and graded on a
      scale of 0-4 as follows: 0, no pain; 1, very mild pain; 2, moderate pain; 3,
      severe pain; 4, intolerable pain. Complications recorded in the first week after
      the procedure were analyzed. They included mild pain, self-limiting hematuria,
      hematospermia, rectal bleeding, severe hematuria, septicemia, severe hemorrhage
      of the anus, and vasovagal attack. RESULTS: Out of 300 TRS-guided biopsies, 10
      early complications were recorded. The most frequent was septicemia, which was
      seen in 5 cases (1.7%). Hematuria occurred in 29 patients, 3 of which were
      severe. Rectal bleeding and vasovagal attack occurred in 1 patient each. All
      patients made a full recovery with appropriate conservative management. Ten cases
      (3.33%) of severe pain (grade 3) and intolerable pain (grade 4) were observed.
      Three out of these 10 patients completed the procedure. The procedure was
      terminated in 1 patient, and 6 patients required local anesthetic due to perianal
      disease. CONCLUSIONS: TRS-guided prostate biopsy can be performed without local
      anesthesia in 90% of patients. Prophylactic antibiotics are mandatory to minimize
      approximately infectious complications.

PMID- 16281271
TI  - Conservative management of live tubal pregnancies by ultrasound guided potassium
      chloride injection and systemic methotrexate treatment.
AB  - Unruptured live tubal ectopic pregnancies are often managed surgically.
      Significantly elevated beta-hCG levels in these patients make treatment with
      methotrexate ineffective. However, achieving cardiac asystole via sonographically
      guided injection of potassium chloride (KCl) along with systemic methotrexate can
      improve treatment outcome. We describe the successful conservative management of
      3 cases of unruptured tubal pregnancy with cardiac activity and significantly
      elevated beta-hCG levels. Under sonographic guidance, KCl was injected into the
      fetal heart to achieve cardiac asystole, and patients concurrently received a
      systemic methotrexate injection. The resolution of ectopic pregnancy was achieved
      and surgery was avoided in all 3 cases. Conservative management may thus be an
      option for patients with live ectopic pregnancies.

PMID- 16281272
TI  - Vein wall dissection: a rare puncture-related complication of brachiocephalic
      fistula. Gray-scale and color Doppler sonographic findings.
AB  - We describe a case of brachiocephalic fistula vein wall dissection (VWD)
      occurring in a 36-year-old female hemodialysis patient. Unlike subcutaneous or
      subfascial infiltrations for which the mechanism is blood extravasation, VWD
      seems to be due to disruption of the fistula vein layers caused by misplacement
      of the outflow (venous) needle bevel. In this setting, the pressure of the
      dialysis blood pump acts as the driving force of the dissecting column, extending
      it proximally. Gray-scale and color Doppler sonography proved to be very useful
      in the differential diagnosis of VWD, particularly with thrombosis of the
      fistula. Sonography also helped us decide when to resume cannulations.

PMID- 16281273
TI  - Squamous cell carcinoma of the liver: metastasis or primary neoplasm?

PMID- 16281274
TI  - Wandering spleen--the challenge of ultrasound diagnosis: report of 7 cases.
AB  - PURPOSE: To summarize our experience with sonographic diagnosis of wandering
      spleen in children and assess for the typical sonographic findings of wandering
      spleen, complications, and possible diagnostic pitfalls. METHODS: We identified
      all pediatric patients from 1998-2003 with a surgically confirmed diagnosis of
      wandering spleen. All sonographic examinations were reviewed for splenic
      position, size, echotexture, and parenchymal blood flow. RESULTS: Seven children
      were identified with a mean age of 9.7 years (range 4.2-15.3 years). All
      presented with abdominal pain. Abdominal sonography, performed in all children
      demonstrated a low position of the spleen (n = 6), splenomegaly (n = 4), and
      absence of parenchymal flow in the three patients with splenic torsion and
      infarction. The diagnosis was made preoperatively via sonography in five
      children; three required repeated hospital admissions before the correct
      diagnosis was established. Complications occurred in five patients (gastric
      obstruction [n = 1], splenic infarction [n = 3], and recurrent pancreatitis [n =
      1]). CONCLUSION: The most specific sonographic finding for wandering spleen is
      low position of the spleen. However, if the spleen regains its normal or near
      normal position, the diagnosis may be missed and the condition may recur, and
      result in complications.

PMID- 16281275
TI  - Electromyographic studies in mdx and wild-type C57 mice.
AB  - The electromyographic (EMG) characteristics of human Duchenne muscular dystrophy
      (DMD) have been well-described. However, to our knowledge, no prior needle
      electromyographic (EMG) studies of motor unit morphology have been undertaken in
      muscles from the mdx mouse, an animal that is genetically homologous to DMD.
      There are significant phenotypic differences between the human and murine
      dystrophic conditions, bringing into question whether the mdx mouse is an
      appropriate animal model for DMD. This study was done in order to characterize
      the EMG findings in mdx mice, compared to normal wild-type mice, and to assess
      for similarities to DMD. The tibialis anterior and gastrocnemius/soleus muscles
      from 34 mice (16 C57 wild-type and 18 mdx), divided into four age groups (3, 12,
      18, and 24 months), were examined. Wild-type muscles showed normal insertional
      activity and no abnormal activity at rest. Motor unit action potential (MUAP)
      parameters were characterized. In contrast to wild-type muscles, mdx muscles
      showed increased insertional activity, abnormal spontaneous potentials, and the
      presence of complex repetitive discharges (CRDs). MUAPs showed increased numbers
      of phases (4.0 +/- 0.6, P < 0.001) and duration (7.1 +/- 1.2 ms, P < 0.02), as
      well as late components (15%). These EMG data indicate that mdx muscles display
      EMG characteristics similar to those found in muscles from boys with DMD, lending
      credence to the mdx mouse as an animal model for this disease. The data obtained
      in this study indicate a potential role for EMG as an in vivo, objective
      measurement tool that could be used longitudinally to monitor the effects of
      therapeutic interventions in mdx mice. This is important as there are few
      objective measures of muscle function in murine models that do not require
      killing the animal.

PMID- 16281276
TI  - An alternative test of electromyographic normalization in patients.
AB  - The value of electromyography (EMG) in the interpretation of normal and
      pathological movement depends on recording, processing, and normalization
      procedures. Traditionally, maximum voluntary isometric contraction (MVIC) of
      individual muscles is commonly used for EMG normalization. However, this is a
      time- and energy-consuming procedure, especially in patients. The aim of the
      present study was to compare an alternative method of recording the MVIC of lower
      limb muscles to the traditional method in healthy, young subjects as well as
      individuals with a stroke. The alternative method consisted of recording the
      maximum effort of several thigh and leg muscles simultaneously using two tasks on
      a dynamometer. Five healthy subjects and five individuals who had a stroke
      performed both MVIC tasks. The healthy group repeated the test 3 h later on the
      same day. In general, the method of computing maximum EMG from the alternative
      MVIC test yielded values that were equal or greater than those from the
      traditional test in both groups. In the healthy group, muscles showed similar
      EMGs in the two sessions, indicating that the test was reliable. These results
      suggest that the less time-consuming alternative method of computing maximum EMG
      values used here provides a reasonable alternative when time and fatigue become
      issues, especially when testing patient populations.

PMID- 16281277
TI  - Short- or long-term effects of adult myoblast transfer on properties of
      reinnervated skeletal muscles.
AB  - Skeletal muscle demonstrates a force deficit after repair of injured peripheral
      nerves. Data from the literature indicate that myoblast transfer enhances
      recovery of muscle function. Thus, we tested the hypothesis that transfer of
      adult myoblasts improves the properties of reinnervated rabbit tibialis anterior
      (TA) muscles in both the short term (4 months) and long term (14 months). Two
      months after transection and immediate suture of the common peroneal nerve, TA
      muscles were made to degenerate by cardiotoxin injection and then transplanted
      with adult myoblasts cultured for 13 days. Under these conditions, muscles
      studied at 4 months were heavier, contained larger fibers, and developed a
      significantly higher maximal force than muscles that had only been denervated
      reinnervated. In the long term, although muscles made to degenerate were heavier
      and developed a significantly higher maximal force than denervated-reinnervated
      muscles, myoblast transfer failed to improve these parameters. However, the
      overall characteristics of long-term operated muscles tended clearly to approach
      those of the controls. Taken together, these results may have significant
      implications in certain orthopedic contexts, particularly after immediate or
      delayed muscle reinnervation.

PMID- 16281278
TI  - Prolonged limb allograft survival with CD 40 costimulation blockade, T-cell
      depletion, and megadose donor bone-marrow transfusion.
AB  - The purpose of this study was to determine the efficacy of a treatment regimen
      consisting of CD 40 costimulation blockade, T-cell depletion, and megadose donor
      bone marrow transfusion in the limb allograft model. C57Bl/6 mice underwent limb
      transplantation from Balb/c mice and received MR1 (anti-CD 40 ligand monoclonal
      antibody), and CD4(+) and CD8(+) T cell-depleting antibodies with and without 120
      x 10(6) donor bone-marrow transfusion. Recipients treated only with antibodies
      showed rejection at 51.4+/-17 (mean+/-SEM) days, while those who also received
      donor bone marrow had allograft survival of 67+/-16.4 days, with a range up to 91
      days. Treated specimens with rejection had less lymphocytic infiltration than
      untreated controls. Recipients of donor bone marrow also demonstrated early mixed
      chimerism, which disappeared after 1 month. While allograft survival was
      prolonged, tolerance was not achieved, and the mechanism of rejection was more
      consistent with a chronic process.

PMID- 16281279
TI  - Microsurgical training curriculum for learning kidney and liver transplantation
      in the rat.
AB  - During the education of the next generation of scientists in experimental
      research, careful instruction in surgical techniques is of major importance. This
      applies in particular to complicated microsurgical models, which require a
      structured teaching concept with clearly laid-down working steps and adequate
      didactic resources. Transplantations in rats are undoubtedly among the most
      difficult models in experimental surgery. Because completely sutured orthotopic
      liver transplantation and kidney transplantation have been practiced for many
      years in our Surgical Research Unit, techniques must be transmitted to future
      generations. A microsurgical training program has been set up with the aim of
      being efficient, transparent, and motivating. Simply learning-by-doing in the
      sense of "laissez-faire" is ineffective and costly. Our training program is based
      on "three-phase didactics," in which the learning targets are presented in
      sequence and are clearly defined. This report is intended to give a brief
      overview of the principal transplantation models and to serve as a guide for
      teaching these models.

PMID- 16281280
TI  - Gradual graft-cell repopulation with recipient cells following vascularized bone
      and limb allotransplantation.
AB  - Little is known about the fate of graft cells following vascularized bone
      allografting. This study was conducted to define the process of graft-cell
      repopulation with recipient cells. Sixty-five vascularized tibial bone and 50
      limb allotransplantations were performed in rat sex-mismatched pairs. FK 506 was
      used for immunosuppression. The ratio of donor and recipient cells in the graft
      was evaluated by semiquantitative polymerase chain reaction, using the Y
      chromosome primers. Allografted bones had no rejection episodes. In the
      vascularized bone allograft model, donor-derived cells were gradually replaced by
      cells of recipient origin, such that by 24 weeks, they comprised only 10% of
      total cells. In the limb allograft model, male recipient cells were detected in
      female grafts not at 1 week but at 48 weeks posttransplantation. The ratio of
      recipient cells was more than 10% in the femur and tibia. Recipient-derived cells
      gradually migrated into the grafted bone cells with the passage of time.

PMID- 16281281
TI  - Preferential occurrence of 1-2 microindels.
AB  - Microindels are unique, infrequent mutations that result in inserted and deleted
      sequences of different sizes (between one and 50 nucleotides) at the same
      nucleotide position. Little is known about the mutational mechanisms that are
      responsible for these mutations. From our database of 6,016 independent somatic
      mutational events in the lacI gene in Big Blue mice, we assembled the 30
      microindels (0.5%) for analysis. Microindels with one nucleotide inserted and two
      nucleotides deleted (1-2 microindels) accounted for seven (23%) of the
      microindels observed, with the remaining microindels distributed among 21 other
      combinations of insertion and deletion sizes. A preferential occurrence of 1-2
      microindels (20%) was also observed in human germline transmitted mutations in
      the Human Gene Mutation Database (HGMD). An examination of the sequence flanking
      the mouse 1-2 microindels did not reveal obvious site specificity or associated
      secondary structure. A detailed examination of 1-2 microindels did not reveal the
      features typical of pure microinsertion and microdeletion events, but rather
      suggested a unique mutational mechanism. The 1 bp insertion in 1-2
      microinsertions, and pure 1 bp insertions show distinct features. The mechanism
      for 1-2 microindels is not obviously a simple combination of pure microinsertion
      and microdeletion events. The dramatic enhancement of 1-2 microindels requires
      explanation. We speculate that certain error-prone polymerases may be responsible
      for the preferential occurrence of 1-2 microindels in both somatic tissues and
      germ cells. It is estimated that a human adult carries roughly 400 billion
      somatic 1-2 microindels with the potential to predispose to cancer.

PMID- 16281282
TI  - NMR structure of protein yqbG from Bacillus subtilis reveals a novel alpha
      helical protein fold.

PMID- 16281283
TI  - Vowel sound extraction in anterior superior temporal cortex.
AB  - We investigated the functional neuroanatomy of vowel processing. We compared
      attentive auditory perception of natural German vowels to perception of nonspeech
      band-passed noise stimuli using functional magnetic resonance imaging (fMRI).
      More specifically, the mapping in auditory cortex of first and second formants
      was considered, which spectrally characterize vowels and are linked closely to
      phonological features. Multiple exemplars of natural German vowels were presented
      in sequences alternating either mainly along the first formant (e.g., [u]-[o],
      [i]-[e]) or along the second formant (e.g., [u]-[i], [o]-[e]). In fixed-effects
      and random-effects analyses, vowel sequences elicited more activation than did
      nonspeech noise in the anterior superior temporal cortex (aST) bilaterally.
      Partial segregation of different vowel categories was observed within the
      activated regions, suggestive of a speech sound mapping across the cortical
      surface. Our results add to the growing evidence that speech sounds, as one of
      the behaviorally most relevant classes of auditory objects, are analyzed and
      categorized in aST. These findings also support the notion of an auditory "what"
      stream, with highly object-specialized areas anterior to primary auditory cortex.

PMID- 16281284
TI  - Identifying human parieto-insular vestibular cortex using fMRI and
      cytoarchitectonic mapping.
AB  - The parieto-insular vestibular cortex (PIVC) plays a central role in the cortical
      vestibular network. Although this region was first defined and subsequently
      extensively studied in nonhuman primates, there is also ample evidence for a
      human analogue in the posterior parietal operculum. In this study, we
      functionally and anatomically characterize the putative human equivalent to
      macaque area PIVC by combining functional magnetic resonance imaging (fMRI) of
      the cortical response to galvanic vestibular stimulation (GVS) with probabilistic
      cytoarchitectonic maps of the human parietal operculum. Our fMRI data revealed a
      bilateral cortical response to GVS in posterior parieto-insular cortex. Based on
      the topographic similarity of these activations to primate area PIVC, we suggest
      that they constitute the functionally defined human equivalent to macaque area
      PIVC. The locations of these activations were then compared to the probabilistic
      cytoarchitectonic maps of the parietal operculum (Eickhoff et al. [2005a]: Cereb
      Cortex, in press; Eickhoff et al. [2005c]: Cereb Cortex, in press), whereby the
      functionally defined PIVC matched most closely the cytoarchitectonically defined
      area OP 2. This activation of OP 2 by vestibular stimulation and its
      cytoarchitectonic features, which are similar to other primary sensory areas,
      suggest that area OP 2 constitutes the human equivalent of macaque area PIVC.

PMID- 16281286
TI  - Spectrum of mutations in mut methylmalonic acidemia and identification of a
      common Hispanic mutation and haplotype.
AB  - Cobalamin nonresponsive methylmalonic acidemia (MMA, mut complementation class)
      results from mutations in the nuclear gene MUT, which codes for the mitochondrial
      enzyme methylmalonyl CoA mutase (MCM). To better elucidate the spectrum of
      mutations that cause MMA, the MUT gene was sequenced in 160 patients with mut
      MMA. Sequence analysis identified mutations in 96% of disease alleles. Mutations
      were found in all coding exons, but predominantly in exons 2, 3, 6, and 11. A
      total of 116 different mutations, 68 of which were novel, were identified. Of the
      116 different mutations, 53% were missense mutations, 22% were deletions,
      duplications or insertions, 16% were nonsense mutations, and 9% were splice-site
      mutations. Sixty-one of the mutations have only been identified in one family. A
      novel mutation in exon 2, c.322C>T (p.R108C), was identified in 16 of 27 Hispanic
      patients. SNP genotyping data demonstrated that Hispanic patients with this
      mutation share a common haplotype. Three other mutations were seen exclusively in
      Hispanic patients: c.280G>A (p.G94R), c.1022dupA, and c.970G>A (p.A324T). Seven
      mutations were seen almost exclusively in black patients, including the
      previously reported c.2150G>T (p.G717V) mutation, which was identified in 12 of
      29 black patients. Two mutations were seen only in Asian patients. Some
      frequently identified mutations were not population-specific and were identified
      in patients of various ethnic backgrounds. Some of these mutations were found in
      mutation clusters in exons 2, 3, 6, and 11, suggesting a recurrent mutation.

PMID- 16281287
TI  - An interactive web database of factor H-associated hemolytic uremic syndrome
      mutations: insights into the structural consequences of disease-associated
      mutations.
AB  - Factor H (FH) is a central complement regulator comprised of 20 short complement
      repeat (SCR) domains. Nucleotide changes within this gene (CFH) have been
      observed in patients with hemolytic uremic syndrome (HUS), and also
      membranoproliferative glomerulonephritis and age-related macular degeneration.
      All parts of FH are affected, but many mutations are clustered in the C-terminal
      part of FH. Up to now, structural analyses of HUS have been based on SCR-20, a
      domain that is involved in FH interactions with C3b, heparin, and endothelial
      cells. In order to identify the structural and functional consequence of HUS
      mutations, further disease-associated mutations were analyzed in terms of
      homology and nuclear magnetic resonance (NMR) models for factor H SCR domains. An
      interactive web database of 54 human HUS-associated mutations and others was
      created from the literature (www.FH-HUS.org). This has comprehensive search and
      analysis tools, integrating phenotypic and genetic data with structural analysis.
      Each mutation can be highlighted on the SCR structure together with the patient
      FH and C3 levels where available. Two new insights were obtained from our
      collection of data. First, phenotypic data on FH clarify our previously-proposed
      classification of Type I and Type II disorders that both lead to HUS, where Type
      I affects FH secretion and folding, and Type II leads to expressed protein in
      plasma that is functionally defective. Second, the new mutations show more
      clearly that SCR domains from SCR-16 to SCR-19 are important for the ligand
      binding activities of FH as well as SCR-20. This FH web database will facilitate
      the interpretation of new mutations and polymorphisms when these are identified
      in patients, and it will clarify the functional role of FH.

PMID- 16281285
TI  - Neural bases of categorization of simple speech and nonspeech sounds.
AB  - Categorization is fundamental to our perception and understanding of the
      environment. However, little is known about the neural bases underlying the
      categorization of sounds. Using human functional magnetic resonance imaging
      (fMRI) we compared the brain responses to a category discrimination task with an
      auditory discrimination task using identical sets of sounds. Our stimuli differed
      along two dimensions: a speech-nonspeech dimension and a fast-slow temporal
      dynamics dimension. All stimuli activated regions in the primary and nonprimary
      auditory cortices in the temporal cortex and in the parietal and frontal cortices
      for the two tasks. When comparing the activation patterns for the category
      discrimination task to those for the auditory discrimination task, the results
      show that a core group of regions beyond the auditory cortices, including
      inferior and middle frontal gyri, dorsomedial frontal gyrus, and intraparietal
      sulcus, were preferentially activated for familiar speech categories and for
      novel nonspeech categories. These regions have been shown to play a role in
      working memory tasks by a number of studies. Additionally, the categorization of
      nonspeech sounds activated left middle frontal gyrus and right parietal cortex to
      a greater extent than did the categorization of speech sounds. Processing the
      temporal aspects of the stimuli had a greater impact on the left lateralization
      of the categorization network than did other factors, particularly in the
      inferior frontal gyrus, suggesting that there is no inherent left hemisphere
      advantage in the categorical processing of speech stimuli, or for the
      categorization task itself.

PMID- 16281288
TI  - Fates of Cdh23/CDH23 with mutations affecting the cytoplasmic region.
AB  - BUS/Idr mice carrying a mutant waltzer allele (vbus) are characterized by splayed
      hair bundles in inner ear sensory cells, providing a mouse homolog of
      USH1D/DFNB12. RT-PCR-based screening for the presence of mutations in mouse
      Cdh23, the gene responsible for the waltzer phenotype, has identified a G>A
      mutation in the donor splice site of intron 67 (Cdh23:c.9633+1G>A: GenBank
      AF308939.1), indicating that two altered Cdh23 molecules having intron-derived
      COOH-terminal structures could be generated in BUS mouse tissues. Immunochemical
      analyses with anti-Cdh23 antibodies showed, however, no clear Cdh23-related
      proteins in vbus/vbus tissues, while the antibodies immunoreacted with
      approximately 350 kDa proteins in control mice. Immunofluorescent experiments
      revealed considerable weakening of Cdh23 signals in sensory hair cell stereocilia
      and Reissner's membrane in the vbus/vbus inner ear, and transmission electron
      microscopy demonstrated abundant autophagosome/autolysosome vesicles, suggesting
      aberrant Cdh23:c.9633+1G>A-derived protein-induced acceleration of lysosomal bulk
      degradation of proteins. In transfection experiments, signal sequence-preceded
      FLAG-tagged transmembrane plus cytoplasmic regions (TMCy) of tissue-specific
      Cdh23(+/-68) isoforms were localized to filamentous actin-rich protrusions and
      the plasma membrane of cultured cells, whereas FLAG-TMCy:c.9633+1G>A proteins
      were highly insoluble and retained in the cytoplasm. In contrast, FLAG-tagged
      TMCy:p.Arg3175His and human TMCy:c.9625_9626insC forms were both localized to the
      plasma membrane in cultured cells, allowing prediction that USH1D-associated
      CDH23:p.Arg3175His and CDH23:c.9625_9626insC proteins could be transported to the
      plasma membrane in vivo. The present results thus suggest different fates of
      CDH23/Cdh23 with mutations affecting the cytoplasmic region.

PMID- 16281289
TI  - Amygdala-prefrontal dissociation of subliminal and supraliminal fear.
AB  - Facial expressions of fear are universally recognized signals of potential
      threat. Humans may have evolved specialized neural systems for responding to fear
      in the absence of conscious stimulus detection. We used functional neuroimaging
      to establish whether the amygdala and the medial prefrontal regions to which it
      projects are engaged by subliminal fearful faces and whether responses to
      subliminal fear are distinguished from those to supraliminal fear. We also
      examined the time course of amygdala-medial prefrontal responses to supraliminal
      and subliminal fear. Stimuli were fearful and neutral baseline faces, presented
      under subliminal (16.7 ms and masked) or supraliminal (500 ms) conditions. Skin
      conductance responses (SCRs) were recorded simultaneously as an objective index
      of fear perception. SPM2 was used to undertake search region-of-interest (ROI)
      analyses for the amygdala and medial prefrontal (including anterior cingulate)
      cortex, and complementary whole-brain analyses. Time series data were extracted
      from ROIs to examine activity across early versus late phases of the experiment.
      SCRs and amygdala activity were enhanced in response to both subliminal and
      supraliminal fear perception. Time series analysis showed a trend toward greater
      right amygdala responses to subliminal fear, but left-sided responses to
      supraliminal fear. Cortically, subliminal fear was distinguished by right ventral
      anterior cingulate activity and supraliminal fear by dorsal anterior cingulate
      and medial prefrontal activity. Although subcortical amygdala activity was
      relatively persistent for subliminal fear, supraliminal fear showed more
      sustained cortical activity. The findings suggest that preverbal processing of
      fear may occur via a direct rostral-ventral amygdala pathway without the need for
      conscious surveillance, whereas elaboration of consciously attended signals of
      fear may rely on higher-order processing within a dorsal cortico-amygdala
      pathway.

PMID- 16281290
TI  - Lateralized functional components of spatial cognition in the avian hippocampal
      formation: evidence from single-unit recordings in freely moving homing pigeons.
AB  - Previous research has revealed that the functional components of spatial
      cognition are lateralized in the forebrain of birds, including the hippocampal
      formation (HF). To investigate how HF cells in the left and right avian brain may
      differentially participate in representations of space, we recorded single-units
      from the HF of homing pigeons as they ran a plus maze for food. The rate maps of
      left HF cells often displayed elongated regions of increased activity in the
      center of the maze and along the maze corridors, whereas right HF cells tended to
      display patches at the ends of maze arms at/near goal locations. Left HF cells
      displayed a higher degree of spatial-specificity compared with right HF cells,
      including higher patch-specificity, higher reliability, and a higher incidence of
      location-correlated activity. Analysis of speed-correlated and trajectory
      dependent activity also revealed significant HF-lateralized differences. Right HF
      cells tended to display significant negative correlations between spike rate and
      speed, although speed-dependent rate maps indicate that this relationship did not
      explain their space-specific activity. Left HF cells displayed a significantly
      higher incidence of trajectory-dependent space-specific activity than was
      observed in the right HF, suggesting that left HF cells may participate in
      navigating among goal locations. Differences in the correlates of left and right
      pigeon HF cells are consistent with unilateral HF-lesion data suggesting that the
      functional components of spatial cognition are lateralized in the avian brain,
      and furthermore, provide a basis for hypotheses regarding how the left and right
      HF support different aspects of spatial cognition.

PMID- 16281291
TI  - Functional connectivity with the hippocampus during successful memory formation.
AB  - Although it is well established that the hippocampus is critical for episodic
      memory, little is known about how the hippocampus interacts with cortical regions
      during successful memory formation. Here, we used event-related functional
      magnetic resonance imaging (fMRI) to identify areas that exhibited differential
      functional connectivity with the hippocampus during processing of novel objects
      that were subsequently remembered or forgotten on a postscan test. Functional
      connectivity with the hippocampus was enhanced during successful, as compared
      with unsuccessful, memory formation, in a distributed network of limbic cortical
      areas-including perirhinal, orbitofrontal, and retrosplenial/posterior cingulate
      cortex-that are anatomically connected with the hippocampal formation. Increased
      connectivity was also observed in lateral temporal, medial parietal, and medial
      occipital cortex. These findings demonstrate that successful memory formation is
      associated with transient increases in cortico-hippocampal interaction.

PMID- 16281292
TI  - Dealing with the shortcomings of spatial normalization: multi-subject
      parcellation of fMRI datasets.
AB  - The analysis of functional magnetic resonance imaging (fMRI) data recorded on
      several subjects resorts to the so-called spatial normalization in a common
      reference space. This normalization is usually carried out on a voxel-by-voxel
      basis, assuming that after coregistration of the functional images with an
      anatomical template image in the Talairach reference system, a correct voxel
      based inference can be carried out across subjects. Shortcomings of such
      approaches are often dealt with by spatially smoothing the data to increase the
      overlap between subject-specific activated regions. This procedure, however,
      cannot adapt to each anatomo-functional subject configuration. We introduce a
      novel technique for intra-subject parcellation based on spectral clustering that
      delineates homogeneous and connected regions. We also propose a hierarchical
      method to derive group parcels that are spatially coherent across subjects and
      functionally homogeneous. We show that we can obtain groups (or cliques) of
      parcels that well summarize inter-subject activations. We also show that the
      spatial relaxation embedded in our procedure improves the sensitivity of random
      effect analysis.

PMID- 16281293
TI  - Are structural biases at protein termini a signature of vectorial folding?
AB  - Experimental investigations of the biosynthesis of a number of proteins have
      pointed out that part of the native structure may be acquired already during
      translation. We carried out a comprehensive statistical analysis of some average
      structural properties of proteins that have been put forward as possible
      signatures of this progressive buildup process. Contrary to a widespread belief,
      we found that there is no major propensity of the amino acids to form contacts
      with residues that are closer to the N-terminus. Moreover, we found that the C
      terminus is significantly more compact and locally organized than the N-terminus.
      This bias, though, is unlikely to be related to vectorial effects, since it
      correlates with subtle differences in the primary sequence. These findings
      indicate that even if proteins acquire their structure vectorially, no signature
      of this seems to be detectable in their average structural properties.

PMID- 16281294
TI  - Entorhinal cortex lesions disrupt fear conditioning to background context but
      spare fear conditioning to a tone in the rat.
AB  - Recent studies have shown that the integrity of the entorhinal cortex (EC) is not
      required for simple contextual conditioning. In background contextual
      conditioning, i.e., when a phasic cue is present during training, the involvement
      of the EC is still a matter of debate. Therefore, the present work further
      examines whether the EC is required for background contextual conditioning using
      a tone as the phasic cue. Rats sustaining either excitotoxic lesions of the EC or
      sham-lesions were trained with one of two procedures differing with respect to
      the predictive value of the tone: a paired procedure in which the tone perfectly
      predicts shock occurrence and overshadows context, and an unpaired procedure in
      which the predictive value of the tone is reduced. Conditioned fear was assessed
      by freezing responses during conditioning, reexposure to the training context,
      and reexposure to the tone in a new context. Postshock freezing was reduced in
      rats with entorhinal lesions. In all rats trained with the paired procedure,
      freezing to the context was low and freezing to the tone was high, suggesting
      that the tone has overshadowed the context during the conditioning session. The
      reverse pattern was observed with the unpaired procedure in sham-operated rats.
      In rats with entorhinal lesions trained with the unpaired procedure, freezing
      responses to the context was markedly reduced. In a new context, however,
      entorhinal-lesioned rats showed higher freezing scores than those of sham
      lesioned rats. Freezing to the tone was unaffected by the lesion irrespective of
      the tone's predictive value. As a whole, these results support the notion that
      the EC is required for normal background contextual freezing.

PMID- 16281296
TI  - Clinical analysis in familial cortical myoclonic tremor allows differential
      diagnosis with essential tremor.
AB  - Familial cortical myoclonic tremor (FCMT) is a rare disorder often leading to a
      wrong clinical diagnosis of essential tremor. Electrophysiological data are
      usually considered to allow a correct diagnosis. We describe a FCMT French family
      with previously unreported clinical features such as sensitivity to glucose
      deprivation, vibration, repetitive visual patterns, and intense visual or
      auditory stimulation and contrasts. Electrophysiological studies of the
      propositus confirm the cortical reflex myoclonus elicited by photic stimulation
      and the absence of epileptic electroencephalographic discharges. We emphasize
      that a precise clinical analysis can lead to a correct diagnosis before
      electrophysiological confirmation. This is also the first-ever report of efficacy
      of levetiracetam in FCMT.

PMID- 16281297
TI  - Pregnancy in dystonic women with in situ deep brain stimulators.
AB  - In the past few years, an increasing number of dystonic patients, of both sexes,
      have undergone insertion of deep brain stimulators (DBS) with consistent
      improvement of their symptoms and enhancement of their quality of life. We
      describe 3 women with dystonia who, after insertion of bilateral globus pallidus
      internus stimulators, succeeded in conceiving and completing pregnancies, 2 of
      them having married. These histories illustrate the significant positive impact
      that DBS can have on women's social relationships. Based on this experience, we
      also provide an overview of some of the issues that might arise in pregnancy and
      during delivery in dystonic women with an in situ deep brain stimulator.

PMID- 16281299
TI  - Geometrical validation of intravascular ultrasound radiofrequency data analysis
      (Virtual Histology) acquired with a 30 MHz boston scientific corporation imaging
      catheter.
AB  - Recently, the plaque characterization field was explored with the use of the
      substrate (frequency domain analysis) rather than the envelope (amplitude or gray
      scale imaging) of the intravascular ultrasound (IVUS) radiofrequency data.
      However, there is no data about the agreement of quantitative outcome between the
      two methods. The aim of this study was to assess the correlation and agreement
      between quantitative coronary ultrasound and the geometrical measurements
      provided by the spectral analysis of ultrasound radiofrequency data [IVUS-Virtual
      Histology (IVUS-VH), Volcano Therapeutics). Twenty-five patients were included in
      this study. The IVUS catheter used was a commercially available mechanical sector
      scanner (Ultracross 2.9 Fr 30 MHz catheter, Boston Scientific) covered with an
      outer sheath. IVUS-VH significantly underestimated lumen [relative difference
      (RD)=14.8+/-5.6; P<0.001], vessel (RD=14.1+/-4.8; P<0.001), and plaque (RD=11.5+/
      10.8; P<0.001) cross-sectional areas (CSAs). Nevertheless, when adjusted for the
      ultrasound propagation delay caused by the sheath, relative differences of
      measurements were remarkably low (0.49%+/-6.3%, P=0.64 for lumen; 2.33%+/-4.6%,
      P=0.007 for vessel; and 4.2%+/-10.4%, P=0.005 for plaque CSA). These data suggest
      that the volumetric output of the IVUS-VH software underestimates measurements
      when acquired with a 30 MHz catheter. However, after applying a mathematical
      adjustment method for the ultrasound propagation delay caused by the outer sheath
      of the 30 MHz catheter, relative differences of direct measurements were
      negligible. These results suggest that ultrasound radiofrequency data analysis
      could provide, aside from precise compositional data, an accurate geometrical
      output.

PMID- 16281300
TI  - IVUS max.

PMID- 16281301
TI  - Changes in the distribution and fine structure of the intralobular blood vessels
      of the submandibular gland in the postnatally developing mouse.
AB  - Previous studies have shown that the blood vessels supplying the endocrine organs
      and the mucosa of the intestinal canals change in terms of not only their
      distribution but also their structure with the development and growth of each
      organ. We examined changes in the distribution and structure of intralobular
      blood vessels, including capillaries, throughout the postnatal development of the
      submandibular gland, an exocrine organ. The mouse submandibular gland from days 0
      (birth) to 49 was investigated chronologically and ultrastructurally. The
      capillaries changed from continuous to fenestrated on day 10, coincident with an
      increase in the number of acini to more than the number of terminal tubules. The
      number of sections of intralobular blood vessels per unit area gradually
      decreased with increasing acinar size and was lowest on day 21 when pups were
      weaned; the same number was maintained from then on. In contrast with the
      reduction in the number of intralobular blood vessels, the number of capillary
      pores appeared to increase gradually. Acinar size increased further till day 28.
      Capillary pore number also increased further, till day 35, apparently in relation
      to the increasing acinar size. These findings suggest that the changes in
      distribution and structure of the intralobular blood vessels in the submandibular
      gland of the postnatally developing mouse are closely related to the development
      of the parenchymal cells in preparation for weaning and sexual maturity.

PMID- 16281302
TI  - Establishment of epidermal cell lines derived from the skin of the Atlantic
      bottlenose dolphin (Tursiops truncatus).
AB  - The Atlantic bottlenose dolphin (Tursiops truncatus), a marine mammal found off
      the Atlantic coast, has become the focus of considerable attention because of an
      increasing number of mortality events witnessed in this species over the last
      several years along the southeastern United States. Assessment of the impact of
      environmental stressors on bottlenose dolphins (BND) has been difficult because
      of the protected status of these marine mammals. The studies presented herein
      focused on establishing epidermal cell cultures and cell lines as tools for the
      in vitro evaluation of environmental stressors on BND skin. Epidermal cell
      cultures were established from skin samples obtained from Atlantic BND and
      subjected to karyotype analysis. These cultures were further characterized using
      immunohistochemical methods demonstrating expression of cytokeratins. By two
      dimensional polyacrylamide gel electrophoresis (2D-PAGE), we observed that the
      proteomic profile of BND skin tissue samples shared distinct similarities with
      that of skin-derived cultures. Epidermal cell cultures were transfected with a
      plasmid encoding the SV40 small t- and large T-antigens, as well as the neomycin
      resistance gene. Five neomycin-resistant clones were isolated and expanded, and
      all of them proliferated at a faster rate than nontransfected BND epidermal
      cultures, which exhibited signs of senescence. Cell lysates prepared from two
      transfected clones were shown to express, by Western blot analysis, both SV40
      tumor antigens. These experimental results are consistent with the concept that
      transfected clones expressing SV40 tumor antigens represent immortalized BND cell
      lines. Epidermal cell lines derived from Tursiops truncatus will provide a unique
      tool for studying key features of the interaction occurring between dolphins and
      the environment in which they live at their most crucial interface: the skin.

PMID- 16281303
TI  - New agents with antimycobacterial activity.
AB  - In this paper, we report that a series of structurally simple a
      halogenoacetamides show potent and excellent antimycobacterial activities against
      drug-sensitive Mycobacterium tuberculosis H(37)Rv and drug-resistant M. avium.

PMID- 16281305
TI  - Synthesis of 5,6-dimethyl-9-methoxy-1-phenyl-6H-pyrido[4,3-b]carbazole
      derivatives and their cytotoxic activity.
AB  - Starting from 2-(6-methoxy-1-methyl-9H-carbazol-2-yl)ethylamine 7 and mixed
      anhydrides of 4-nitrobenzoic acid or 4-methoxybenzoic acid, the corresponding 5,6
      dimethyl-9-methoxy-1-(4-substituted phenyl)-6H-pyrido[4,3-b]carbazoles 11a-b, 5,6
      dimethyl-9-hydroxy-1-(4-substituted phenyl)-6H-pyrido[4,3-b]carbazoles 12a, 12c,
      and their quaternary salts 13a-d were obtained. The four new pyridocarbazole
      derivatives 12a-c and 13d satisfy the international activity criterion for
      synthetic compounds, namely an ID(50) value lower then 4 microg/mL in preliminary
      in vitro cytotoxic activity screening against the A549 cell line (non-small cell
      lung cancer).

PMID- 16281304
TI  - Synthesis by microwave irradiation and antidiarrhoeal activity of benzotriazinone
      and saccharine derivatives.
AB  - The synthesis by microwave irradiation and the biological results of novel
      benzotriazinone and saccharine derivatives with potential antidiarrhoeal activity
      is described. Conventional and microwave heatings were compared for the
      reactions. Good yields and short reaction times are the main advantages of our
      synthetic route. Among the tested compounds, compound 12 inhibited motility both
      in in-vitro and in-vivo tests.

PMID- 16281306
TI  - Stereoisomers of compounds with symmetric constitutions.
AB  - Chiral organic compounds with unsymmetric constitutions can lead to N(r) = 2(n)
      stereoisomers. By contrast, if a chiral compound has a symmetric constitution,
      then the number of stereoisomers is reduced. In this publication, we wish to
      present an algorithm to calculate the number of stereoisomers of chiral organic
      compounds of the latter type (e. g. sugar acids). The first step is the
      development of two different functions for unbranched compounds where the number
      of repeating units is even or uneven. Other stereogenic units like double bonds,
      chiral axes or planes are not discussed. The results are then checked against the
      actual isomers. The next step leads to a unified equation to predict the precise
      number of stereoisomers that can exist. Thus, the relationship between chirality
      and symmetry is shown in detail. Additionally, the algorithm is applied to some
      drug molecules with symmetric constitutions.

PMID- 16281307
TI  - Synthesis and antiplatelet activity of new imidazole-4-carboxylic acid
      derivatives.
AB  - 1-Arylalkyl-5-phenylsulfonamino-imidazole-4-carboxylic acid esters and their
      carboxamides with an additional secondary amino group were synthesized and
      identified as antiplatelet agents in a low micromolar range (Born-test, inducer
      collagen). To describe the mechanism of action more precisely the Born-test was
      carried out as well with ADP, adrenaline or PAF, respectively. In addition, two
      compounds were investigated for their COX-1 inhibitory activities. Provided the
      essential structural criteria are met i.e. amide group or ester, sulfonylamino
      rest, hydrophobic moieties, and a secondary amino function, slight structural
      modifications are able to shift the pattern of activity among the above platelet
      receptors. So, the ester 5c exhibits PAF antagonistic activity at IC(50) = 1
      microM and COX-1 inhibition (IC(50) = 0.4 microM). The carboxamide 6c shows ADP
      antagonistic properties (IC(50) = 2 microM). Compound 6g is as well PAF
      antagonistic (IC(50) = 4 microM) and a COX-1 inhibitor (IC(50) = 1 microM). The
      derivative 6i shows a strong antiadrenergic (IC(50) = 0.15 microM) and PAF
      antagonistic (IC(50) = 0.66 microM) effect.

PMID- 16281308
TI  - New pyrimido[5,4-c]cinnolines with antiplatelet activities.
AB  - Twenty one new pyrimido[5,4-c]cinnolines containing different lipophilic moieties
      (viz. phenyl, 4-methoxyphenyl, 2-furanyl, 2-thienyl) in position 2 and additional
      basic groups (e.g., alkylaminopropyl, dialkylaminopropyl and
      cyclohexylaminopropyl) in position 4 of the title ring system have been prepared
      and investigated for antiplatelet effects (Born test). Ten of them inhibited the
      platelet aggregation induced by collagen with an IC(50) below 10 micromol/L (6a,
      6b, 6c, 6g, 6h, 6i, 6k, 6m, 6q, 6u). A closer inspection of the antiplatelet
      effect with other inducers showed antagonism against adrenaline (6m), ADP
      antagonist (6i) and PAF antagonist activities (6m, 6i, 6u) in nanomolar (IC(50))
      concentration ranges.

PMID- 16281309
TI  - Synthesis and biological activity of novel acyclic versions of Neplanocin A.
AB  - Novel acyclic Neplanocin A analogues were designed and synthesized. The coupling
      of the alkyl bromide with nucleosidic bases (T, U, 5-FU, 5-IU, C, A) and
      desilylation afforded a series of novel acyclic nucleosides. The synthesized
      compounds were evaluated for their antiviral and antitumor activity.

PMID- 16281311
TI  - Synthesis and antiviral evaluation of novel exomethylene acyclic nucleosides and
      phosphonic acid nucleosides.
AB  - This paper describes a very simple synthesis route of novel acyclic nucleosides
      and phosphonic acid nucleosides. The condensation of the mesylates 6 and 17 with
      the natural nucleosidic bases (A, C, U, T) under nucleophilic substitution
      (K(2)CO(3), 18-Crown-6, DMF) and deprotection afforded the target nucleosides
      (11, 12, 13, 14) and phosphonic acid nucleosides (22, 23, 24, 25). In addition,
      these compounds were evaluated for their antiviral properties against various
      viruses. Uracil derivative 24 shows significant anti-HCMV activity (EC(50) =
      10.24 microM).

PMID- 16281310
TI  - The topical protective effect of soybean-germ oil against UVB-induced cutaneous
      erythema: an in vivo evaluation.
AB  - The preparation and detailed composition of an oil newly extracted from pure soy
      germ (not less than 96 % hypocotyle) are presented. Experiments in vivo showed
      that soybean-germ oil (SGO) possesses a remarkable protective activity against
      UVB-induced skin inflammation, exceeding that of tocopherol acetate by a factor
      of 2. These results suggest that SGO might have interesting therapeutic and
      cosmetic applications in the management of skin diseases initiated, sustained, or
      exacerbated by an over production of free radicals.

PMID- 16281313
TI  - Springlike nanohelical structures in chiral block copolymers.

PMID- 16281312
TI  - Synthesis and anti-HCMV activity of novel 5'-norcarboacyclic nucleosides.
AB  - A very simple route for synthesizing a novel carboacyclic version of 5 cent
      noraristeromycin is described. Condensation of the mesylates 9 and 23 with the
      natural nucleosidic bases (A, U, T, C) under standard nucleophilic substitution
      (K(2)CO(3), 18-Crown-6, DMF) and deblocking conditions, afforded the target
      nucleosides 14, 15, 16, 17, 28, 29, 30, and 31. In addition, these compounds were
      evaluated for their antiviral properties against various viruses.

PMID- 16281314
TI  - Controlled autocatalytic nitration of phenol in a microreactor.

PMID- 16281315
TI  - Mild and chemoselective peptide-bond cleavage of peptides and proteins at azido
      homoalanine.

PMID- 16281316
TI  - Dynamic combinatorial libraries of dye complexes as sensors.

PMID- 16281317
TI  - Indole-based macrocycles as a class of receptors for anions.

PMID- 16281318
TI  - Synthesis of ansa-[n]silacyclopentadienyl-cycloheptatrienyl-chromium complexes (n
      = 1, 2): novel precursors for polymers bearing chromium in the backbone.
AB  - Reaction of [(eta5-C5H4Li)(eta7-C7H6Li)Cr]tmeda with a variety of
      dialkyl(dichloro)silanes in aliphatic solvents afforded the corresponding
      [1]silatrochrocenophanes. Structural characterization by X-ray diffraction
      analysis of the [1]silatrochrocenophanes bearing Me2Si, (iPr)2Si, and
      silacyclobutane bridges revealed tilt angles alpha of 15.56(12) degrees , 15.8(1)
      degrees , and 16.33(17) degrees , respectively. Analogously, a
      [2]silatrochrocenophane (6) was prepared in excellent yield by reaction of [(eta5
      C5H4Li)(eta7-C7H6Li)Cr]tmeda with 1,2-dichloro-1,1,2,2-tetramethyldisilane. This
      complex also was characterized structurally and exhibited a tilt angle alpha of
      2.60(15) degrees. The [1]silatrochrocenophane bearing the Me2Si bridge underwent
      facile and regioselective carbon-silicon bond cleavage with [Pt(PEt3)4] to give a
      very high yield of an oxidative addition product. The ring-opening polymerization
      of these novel [1]silatrochrocenophanes afforded ring-opened chromium-based
      polymers.

PMID- 16281319
TI  - Fine tuning of the electronic properties of linear pi-conjugated oligomers by
      covalent bridging.
AB  - A series of oligothienylenevinylenes, pi-conjugated oligomers rigidified by
      ethylene bridges attached at different sites of the conjugated backbone, have
      been constructed by multistep synthetic methodologies. Electronic absorption
      spectra show that the rigidification of the conjugated system produces a
      bathochromic shift of the absorption maximum and a narrowing of the HOMO-LUMO
      energy gap, as compared to the spectra of an open-chain reference compound. The
      cyclic voltammograms of all oligomers show that these compounds can be reversibly
      oxidized into their cation radicals and dications and that rigidification
      produces a large negative shift of the first oxidation potential, which is
      indicative of a considerable increase of the HOMO level. Electrochemical data
      confirm that covalent bridging strongly affects the HOMO and LUMO levels and
      these data demonstrate that the sites of fixation of the bridges on the pi
      conjugated backbone exert a determining effect on the relative stability of the
      cation radical and dication. Examination of these various results in the light of
      theoretical calculations shows that in addition to a local control of bond length
      alternation, and hence of the HOMO-LUMO gap, the fixation of covalent bridges at
      selected positions of the pi-conjugated system limits the deformation of the pi
      conjugated structure upon oxidation to the charged states.

PMID- 16281320
TI  - Preferred 3D-structure of peptides rich in a severely conformationally restricted
      cyclopropane analogue of phenylalanine.
AB  - Terminally blocked, homo-peptide amides of (R,R)-1-amino-2,3-diphenylcyclopropane
      1-carboxylic acid (c3diPhe), a chiral member of the family of Calpha
      tetrasubstituted alpha-amino acids, from the dimer to the tetramer, and
      diastereomeric co-oligopeptides of (R,R)- or (S,S)-c3diPhe with (S)-alanine
      residues to the trimer level were prepared in solution and fully characterized.
      The synthetic effort was extended to terminally protected co-oligopeptide esters
      to the hexamer, where c3diPhe residues are combined with achiral alpha
      aminoisobutyric acid residues. The preferred conformations of the peptides were
      assessed in solution by FT-IR absorption, NMR, and CD techniques, and for seven
      oligomers in the crystal state (by X-ray diffraction) as well. This study clearly
      indicates that c3diPhe, a sterically demanding cyclopropane analogue of
      phenylalanine, tends to fold peptides into beta-turn and 3(10)-helix
      conformations. However, when c3diPhe is in combination with other chiral
      residues, the conformation preferred by the resulting peptides is also dictated
      by the chiral sequence of the amino acid building blocks. The (S,S)-enantiomer of
      this alpha-amino acid, unusually lacking asymmetry in the main chain, strongly
      favors the left-handedness of the turn/helical peptides formed.

PMID- 16281321
TI  - New evidence confirms dangers of physician self-referrals to specialty hospitals.
      Legislators side with community hospitals over objections to self-referral abuse.

PMID- 16281322
TI  - Pump-noise transfer in optical parametric chirped-pulse amplification.
AB  - We report on direct observation of temporal contrast degradation of short pulses
      amplified by optical parametric chirped-pulse amplification. We show that,
      despite injection seeding, quantum-noise-induced fast modulations (< 50 ps) of
      the temporal profile of the pump pulse are imprinted on the spectrum of the
      amplified chirped pulse and give rise to a large picosecond pedestal in the time
      domain.

PMID- 16281323
TI  - Influence of mechanical properties of two resin cements on durability of bond
      strength to dentin after cyclic loading.
AB  - The purpose of this study was to evaluate how the different mechanical properties
      of two luting agents (acrylic resin cement and resin composite cement) influenced
      their bond strength to dentin, after cyclic loading that simulated chewing.
      Stainless steel rods were bonded to the flattened dentin surfaces with each
      luting agent. After immersion in water for 24 hours, half the specimens of each
      group were tested for tensile bond strength and the remaining half were subjected
      to a vertical load (75.6 N, 1.2 Hz) using an acrylic stylus--which upon contact
      with the specimen would rotate counterclockwise and then counter-rotate. Bond
      strength of the resin composite cement with self-etching was found to be
      significantly lower than the other adhesive systems. After 100,000 cycles, the
      bond strength of resin composite cement was significantly decreased while acrylic
      resin cement showed no decrease in bond strength.

PMID- 16281324
TI  - Basic evaluation of cast joining for electroformed coping using multi-purpose
      alloys.
AB  - The purpose of this study was to evaluate the bonding interface and bonding
      strength of electroformed coping when cast joining was used with a multi-purpose
      alloy. The multi-purpose alloy was cast at a mold temperature of 700, 750 or 800
      degrees C. A high noble alloy tab was also soldered onto an electroformed coping
      as a control. Sectioned surfaces of cast joining and soldered specimens were
      observed using a scanning electron microscope and analyzed using an electron
      probe micro analyzer. Shear bonding strength of specimens cast at 750 degrees C
      and that of soldered specimens were determined. The edge of the cast joining
      alloy was round, but this improved as temperature increased. Diffusion of
      elements from the cast joining alloy and electroformed coping was detected at the
      interface, which contributed to a significantly higher bonding strength in the
      cast joining specimen than in the soldered specimen. These results suggested that
      the cast joining could be potentially employed for electroformed copings.

PMID- 16281325
TI  - Small angle neutron scattering observation of chain retraction after a large step
      deformation.
AB  - The process of retraction in entangled linear chains after a fast nonlinear
      stretch was detected from time-resolved but quenched small angle neutron
      scattering (SANS) experiments on long, well-entangled polyisoprene chains. The
      statically obtained SANS data cover the relevant time regime for retraction, and
      they provide a direct, microscopic verification of this nonlinear process as
      predicted by the tube model. Clear, quantitative agreement is found with recent
      theories of contour length fluctuations and convective constraint release, using
      parameters obtained mainly from linear rheology. The theory captures the full
      range of scattering vectors once the crossover to fluctuations on length scales
      below the tube diameter is accounted for.

PMID- 16281326
TI  - Arm retraction potential of branched polymers in the absence of dynamic dilution.
AB  - We study the stress relaxation of model polymer networks containing low contents
      of star shaped and linear dangling polymers. As compared with their melts, the
      behavior of star and dangling polymers leads to a dynamic response with
      unprecedented large relaxation times. By comparing data of star melts with those
      corresponding to stars and dangling chains residing in polymer networks, we were
      able to identify the effects of dynamic dilution clearly. Since in polymer
      networks the dynamic dilution effect is suppressed, we were able by the first
      time to experimentally test the validity of the potential for arm retraction
      proposed by Pearson and Helfand.

PMID- 16281327
TI  - Decision making for incompetent patients: who decides and by what standards?

PMID- 16281328
TI  - Patient autonomy and biomedical research: judicial compromise in Moore v. Regents
      of the University of California.

PMID- 16281329
TI  - Genes, parents, and assisted reproductive technologies: ARTs, mistakes, sex,
      race, and law.

PMID- 16281331
TI  - The white world of nursing homes: the myriad barriers to access facing today's
      elderly minorities.
AB  - In this note, Ms. Aeschleman explores the cultural, social, and economic barriers
      faced by elderly minorities in need of nursing home care. Ms. Aeschleman argues
      that minority elders face greater economic barriers to nursing home access than
      Whites because of factors such as lower average incomes and a lack of access to
      and assistance with government programs. Culturally, Ms. Aeschleman argues that
      minorities face barriers to nursing home care because of language differences,
      the location of nursing homes within communities, traditions, and both overt and
      indirect acts of discrimination from nursing home staff, administrators, and
      White clients. Following a discussion of these barriers, Ms. Aeschleman suggests
      options to give elderly minorities equal access to nursing homes through federal
      and state incentives, as well as community-based activism and awareness
      campaigns.

PMID- 16281330
TI  - Disputes over frozen preembryos and the "right not to be a parent".

PMID- 16281332
TI  - Toxic epidermal necrolysis and clarithromycin.
AB  - Toxic epidermal necrolysis almost always occurs after taking a medication.
      Despite spectacular clinical signs, it is mainly diagnosed with pathologic
      techniques. The identification of a drug as the cause for the immune related
      cytotoxic reaction can be difficult if the molecule is not generally known to be
      a classical cause of this reaction. The present study describes a female patient
      who rapidly developed a severe bullous skin disease after taking clarithromycin
      for tonsillitis. The case illustrates the process involved in attributing
      causality to a molecule using an established imputability assessment framework.

PMID- 16281333
TI  - Medical treatment for Asian immigrant children--does mother know best?

PMID- 16281335
TI  - Vascular Burden of the Brain: New Therapeutic Directions. Proceedings of an IPA
      expert consensus conference, Madrid, Spain, November 2001.

PMID- 16281334
TI  - What should the law say about disclosure of genetic information to relatives?

PMID- 16281336
TI  - The argument against a physician's duty to warn for genetic diseases: the
      conflicts created by Safer v. Estate of Pack.

PMID- 16281337
TI  - Old law meets new medicine: revisiting involuntary psychotropic medication of the
      criminal defendant.

PMID- 16281338
TI  - Choosing substantive justice: a discussion of "choice," "rights" and the new
      reproductive technologies.

PMID- 16281339
TI  - Surrogacy: a last resort alternative for infertile women or a commodification of
      women's bodies and children?

PMID- 16281340
TI  - Criminal penalties for women engaging in substance abuse during pregnancy.

PMID- 16281342
TI  - [Problems of radiation exposure in X-ray computed tomography and optimization of
      exposure dose].

PMID- 16281341
TI  - Inverting the viability test for abortion law.

PMID- 16281343
TI  - Abrogating stare decisis by statute: may Congress remove the precedential effect
      of Roe and Casey?

PMID- 16281344
TI  - [Understanding of patient dose information and patient size adjustment].

PMID- 16281345
TI  - [Setting scan conditions for contrast enhanced abdominal CT with viewpoint on
      disease].

PMID- 16281347
TI  - [Optimization of the imaging display for each patient in computed tomography].

PMID- 16281346
TI  - [Optimization of image quality by CT scanner automatic exposure control systems].

PMID- 16281348
TI  - [The Friday lections of J.M. Charcot].
AB  - Studies of the life and work of Jean Martin Charcot (1825-1893) carried out over
      the last fifteen years all see in him one of the figures mainly responsible for
      the constitution of clinical neurology as a specific area of research, in
      particular in French-speaking areas. The aim of this study is to analyse, by the
      use of computational linguistic technique, the language of his lessons to
      demonstrate a rhetoric use of verbs to obtain the verdict from the jury of
      disciplines: the disease's name.

PMID- 16281349
TI  - [Operationalized psychodynamic diagnostic (OPD)--potential for quality
      assurance].
AB  - OBJECTIVES: Psychotherapy is subjected to the legal conditions of quality
      assurance(QA). Does operationalized psychodynamic diagnostics (OPD) contribute
      substantially to this? METHODS: We investigated the application of OPD in
      outpatient psychodynamic psychotherapy, inpatient treatment, rehabilitation, and
      legal assessment. RESULTS: Psychodynamic diagnostics, treatment plan, and
      evaluation by means of the OPD and Heidelberg Structural Change Scale (HSCS) may
      be comprehensibly described for quality assurance (QA) of outpatient and
      inpatient psychotherapy. Virtually all psychodynamic conceptualized departments
      for psychosomatic medicine and psychotherapy as well as some rehabilitation
      centres applied OPD. Furthermore, data-collection periods were defined during and
      after inpatient short- and long-term psychotherapy. OPD serves QA in legal
      assessment and is of a pivotal significance in judicial proceedings. CONCLUSIONS:
      It must be deliberated whether more extensive use of QA, in cooperation with
      outpatient psychotherapists and in comparison to institutions, could be of
      benefit to patients.

PMID- 16281350
TI  - [Unperfect, handicapped persons: for a history of didactics of neuro and
      psychomotor rehabilitation of children in Italy].
AB  - The history of paediatrics disability and of the attempts at creating a
      "rehabilitation strategy" for disabled children, in Italy, has yet to be written.
      This contribution is part of a project involving medical historians,
      psychologists and neurologists, all from Rome University "La Sapienza".

PMID- 16281351
TI  - [A documentation form for the consultation-liaison service: development of the CL
      BaDo].
AB  - OBJECTIVES: In consultation liaison (CL) psychiatry and psychosomatics a
      multicenter documentation form for the assessment of clinical characteristics of
      patients and CL service delivery is urgently needed for health care planning and
      future mental health research. METHODS: In several steps a joint working party of
      the psychosomatic and psycho-therapeutic societies in Germany (German College for
      Psychosomatic Medicine, German Society of Psychosomatic Medicine and
      Psychotherapy, General Medical Society for Psychotherapy) developed a
      documentation form for C-L service (CL-BaDo). The goals and quality criteria of
      the patient registration form are defined in an extended consensus process of C-L
      experts. A pool of formerly 60 items was reduced to 36 items collecting data
      concerning sociodemographic characteristics, referral information, anamneses,
      actual psychiatric and somatic status and diagnoses, C-L interventions and
      treatment recommendations. To enable comparisons, the formulation of items are
      adapted to existing inpatient and outpatient documentation forms (Psy-BaDo,EuroQA
      CL). A special manual guides the coding of the CL-BaDo. RESULTS: 16 CL services
      in Germany and Austria participated in the testing and pilot study of six months
      demonstrating the comprehensibility and fast completion of CL-BaDo and
      consultants' high acceptance of the form. A time-saving and user-friendly
      electronic version for data entry and data analyses was developed using hand-held
      technology. CONCLUSION: The data of the CL-BaDo can be used for 1) quality
      management and communication purposes with referring departments and 2) for
      multicenter collaborative studies, mental health care management and care
      planning.

PMID- 16281352
TI  - Sweet collaborations.

PMID- 16281353
TI  - Tackling biology's big question.
AB  - Working from opposite ends of the protein folding problem, two research teams
      have developed powerful mathematical strategies that offer the potential to
      greatly clarify the relationship between primary sequence and native structure.

PMID- 16281355
TI  - Uncovering hidden relationships.
AB  - Two new studies tackle the complexities of synthetic genetic interaction-
      identifying relationships between gene products that interact functionally rather
      than physically.

PMID- 16281354
TI  - Splitting hairs.
AB  - A dual-transgenic mouse with localized expression of two different fluorescent
      markers is the foundation for an inventive strategy for dissecting hair follicles
      and isolating their component cell populations.

PMID- 16281357
TI  - Labeling on the surface.
AB  - A strategy for labeling cell-surface proteins in living cells with small-molecule
      fluorophores allowed scientists to study receptor trafficking by single-cell FRET
      imaging in real time.

PMID- 16281356
TI  - A synthetic solution to gene delivery.
AB  - A self-assembling polymer-DNA nanoparticle serves as a vehicle for highly
      efficient gene delivery to cells.

PMID- 16281358
TI  - Proceedings of the International Symposium on Growth Hormone, Santiago de
      Compostela, Spain, 18-20 November 2004.

PMID- 16281359
TI  - Therapeutic resistance in breast cancer: Impact of growth factor signalling
      pathways and implications for future treatment. Proceedings of the 1st
      Tenovus/AstraZeneca workshop, 3-4 February 2005, Cardiff, United Kingdom.

PMID- 16281360
TI  - [How to confirm or exclude the existence of cirrhosis of the liver?].

PMID- 16281361
TI  - [Legislative base on occupational medicine in Russian Federation].

PMID- 16281362
TI  - [Justifying hyperbaric oxygenation use for medical correction in individuals
      working in extreme conditions].
AB  - Experimental studies were conducted to justify possibility of hyperbaric
      oxygenation to correct functional state in individuals working in extreme
      conditions. Studies were aimed to determine stress resistance in apparently
      healthy individuals, to choose hyperbaric oxygenation method and mode.

PMID- 16281364
TI  - [Influence of industrial pollutants on bronchial permeability].
AB  - Findings are that prevalence of COLD among workers of chemical industrial complex
      in Kemerovo city, who contact organic chemicals, is 1.6 times higher than that
      among those in contact with irritants and 5.4 times higher than that in reference
      group. Chemical industry workers develop dysbalance of pro- and antioxidant
      processes, that is maximal in those contacting organic solvents.

PMID- 16281363
TI  - [Peculiarities of relationships between throat microflora and immune state among
      residents of areas with various antropogenous loads].
AB  - The work covered state of normal throat microflora in accordance with immune
      state among individuals long residing in areas with various technogenic loads.
      The authors revealed both general and specific changes in quantitative and
      qualitative contents of normal throat microflora in accordance with cellular and
      humoral immunity, as well as with industrial factors.

PMID- 16281365
TI  - [Occupational morbidity in Ukraine].
AB  - The authors analyzed occupational morbidity in Ukraine over 1990-2003, in
      comparison with european data. Regions with higher and lower occupational
      morbidity were identified. Analysis covered occupational diseases for certain
      industries in accordance with exposure to dust, chemicals, noise, vibration,
      physical strain.

PMID- 16281366
TI  - [Evaluating possibility of free radicals formation in decomposition of mullite
      and kaolin as a factor determining cytotoxicity of high-alumina refractories].

PMID- 16281367
TI  - [External respiration parameters in workers engaged in synthetic detergents
      production].
AB  - The study covers results of thorough clinical and functional examination of
      workers engaged into contemporary chemical production. The authors studied
      effects caused in immunity parameters, respiratory organs and skin by sensitizing
      and irritating chemicals. Findings are that the most significant changes in
      external respiration parameters and high predisposition to respiratory diseases
      are associated with specific sensitizing to industrial allergen and with higher
      IgE levels.

PMID- 16281369
TI  - [Acute toxic effects of chemical reagents used in petroleum production].

PMID- 16281368
TI  - [Respiration biomechanics in patients with berylliosis and chronic toxico
      chemical bronchitis].

PMID- 16281370
TI  - [Health state of workers engaged in mining industry].

PMID- 16281371
TI  - [Immune state in workers contacting occupational hazards].

PMID- 16281372
TI  - [Sleep-related breathing disturbances in motor neuron disease].
AB  - Presented are the results of the study of respiratory parameters, together with
      standard polysomnography, in 18 patients with motor neuron disease (13 males, 5
      females, mean age 61,5 +/- 10,6 years). AHI =10 epis./h was found in 10 (56%)
      cases. Other 4 patients demonstrated a low level (less 94%) of average blood
      saturation during sleep. The highest number of obstructive episodes was observed
      in patients with progressive bulbar palsy and amyotrophic lateral sclerosis (ALS)
      with bulbar signs. The lowest level of nighttime saturation was registered in
      patients with ALS without bulbar signs. Mean saturation (less than 94%) was
      associated with more pronounced limb muscle weakness, rapid disease progression
      and worse survival.

PMID- 16281373
TI  - [Changes of the thyroid hormone status in children with cerebral palsy and other
      neurological pathology].
AB  - Content of thyroid hormones (T3 and T4) and thyrotropin (TTG) hormone in blood
      plasma has been studied in 142 children with neurological pathology (cerebral
      palsy, perinatal CNS lesion). In most cases, there was a significant increase of
      T3 and T4 and reduction of TTG as compared to control group of healthy children.
      The changes of thyroid hormones content depended on the patient's age and
      severity of a pathological condition. A mother pregnancy course impacted on the
      hormones level. The content of T3 and T4 in blood plasma was higher in case of
      cystitis in mother's anamnesis or a persistent threat of preterm delivery. In
      patients, a TTG reduction correlated with mental retardation. In those with
      marked dysplasia of osseous tissue (osteoclast, osteopathy), the TTG content was
      higher comparing to patients without such malformations.

PMID- 16281374
TI  - [Reminyl efficacy in dementia with Levi bodies].
AB  - Reminyl (galantamine)-- a cholinesterase inhibiting component--was used in
      treatment of 15 patients with dementia featured by the presence of Levi bodies in
      brain neurons. The treatment duration was 16 weeks with elevation of the drug
      dosage every 4 weeks--from 8mg to 12 mg twice a day. Treatment evaluation was
      conducted clinically and by psychometrical tests and scales. Reminyl improved
      patient's state reducing cognitive, behavioral and psychotic disturbances. The
      highest effect was achieved in 2/3 patients. Side-effects (nausea, dizziness,
      dyspepsia, general sickness, etc) were observed in 47% cases. Only in 2 patients
      they caused treatment withdrawal. The absence of aggravation of extrapyramidal
      disorders is emphasized.

PMID- 16281375
TI  - [Comparative efficacy and tolerability of paroxetine and amitriptiline in long
      term therapy preventing depressive recurrences].
AB  - An open comparative randomized study of paroxetine (selective inhibitor of
      serotonin re-uptake) and tricyclic antidepressant amitriptiline has been
      conducted. These drugs were used for the treatment of 43 patients with recurrent
      depression (RD) with frequent relapses (ICD-10 F33.0-F33.2) during 12 months.
      There were 2 groups matched for demographic and clinical data, one included 21
      patients treated by paroxetine and the other 22 patients switched to
      amitriptiline. Basing on clinical records and scores on a number of scales, i.e.
      HAM-D, CGI, quality of life, high efficacy of the drugs was confirmed, being
      estimated as 90,5% responders in the paroxetine group and 69,2% in the
      amitriptiline one, with the marked advantage of the former medication. The better
      tolerability, possibility of single intake and absence of severe side-effects
      argue for preferable use of paroxetine during long-term therapy in RD patients
      with frequent relapses.

PMID- 16281376
TI  - [Blood serum of patients with secondary progressive multiple sclerosis changes
      neuron electric activity].
AB  - An effect of 20% blood serum estimated by the changes of background and excited
      spike activity of Retzius' neuron by Hirudo medicinalis, which does not contain
      myelin, has been studied in 2 groups of patients. The first group comprised
      patients with serum, containing antibodies to gangliosides, and the second one-
      patients without such antibodies. Incubation of Reitzius neurons in the serum
      with GM1-antibodies within 40 min resulted in the change of spike form, increase
      of cell stimulation threshold by average 20%, reduction of the frequency of
      spontaneous impulse activity by average 28%, decrease of the spikes number in
      response to the lower frequency (0.5 Hz) synaptic stimulation and inhibition of
      adaptation to the high frequency (10 Hz) stimulation. The use of the serum
      without GM1-antibodies caused a different change of the spike form and increased
      the stimulation threshold by 8% and sparser background impulse activity of the
      neuron by 40%. During low frequency synaptic activation of the neuron (0.5%),
      there was sensitivity disturbance and inhibition of the electric response to the
      high frequency stimulation. The results suggest that neuron injuries in multiple
      sclerosis may develop before morphological appearances of myelin lesions.

PMID- 16281377
TI  - [A study of some genes related to serotoninergic and dopaminergic systems and
      auditory evoked-potentials (P300) in patients with schizophrenia and spectrum
      disorders and their first-degree relatives].
AB  - The changes of P300 parameters (lower amplitude and increased latency) are
      thought to be the most prominent phenomena of schizophrenia. A role of gene
      polymorphism in P300 generation was supported by several associative studies in
      psychiatrically well subjects and patients with mental disorders. We studied P300
      parameters and the following polymorphisms: T102C for the serotonin receptor type
      2A (5-HTR2A) gene, the 5-HTTLPR for the serotonin transporter gene, -809G/A, 
      616G/C N -52C/T SNPs in the promoter region of the dopamine D4 receptor (DRD4)
      gene and the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) in
      74 patients with schizophrenia and spectrum disorders and 71 their first-degree
      relatives. No association was found between serotonergic system genes and P300.
      The -809G/A DRD4 gene polymorphism was related to amplitude in all frontal leads
      (p=0,01) in patients. In relatives, an association was observed between -521C/T
      DRD4 variants and latency (p=0,005) as well as between the COMT gene polymorphism
      and P300 amplitude (p=0,004) at the central lead. Thus, the genes involved in
      dopaminergic system play a role in P300 generation both in patients with
      schizophrenia and spectrum disorders and their relatives.

PMID- 16281378
TI  - [Relation between immunological and neurophysiologic markers during exacerbation
      of schizophrenic process].
AB  - Relation between leukocyte elastase (LE) activity of peripheral blood and
      temporal parameters of late cognitive component of event-related potentials (ERP)
      was studied in 36 patients with different types of schizophrenia and 28 healthy
      controls. Both P300 latency and amplitude correlated with LE activity in
      patients, but not in controls. The results suggest a relationship between innate
      immunity activation and pathophysiologic processes underlying cognitive
      impairment in schizophrenia. Possible mechanisms of the correlations revealed are
      analyzed.

PMID- 16281379
TI  - [Executive system of psychiatric service and improvement of its efficiency on
      regional level].

PMID- 16281380
TI  - [G.I. Rossolimo--a founder of the first Russian battery for personality and
      intellect testing].

PMID- 16281381
TI  - [Anticonvulsive pharmacotherapy may aggravate epilepsy course].

PMID- 16281383
TI  - [Higher mental functions in Chernobyl liquidators].

PMID- 16281382
TI  - [Azaphen: a return to clinical practice].

PMID- 16281385
TI  - [Natural history and rational treatment of epilepsy].

PMID- 16281384
TI  - [Neuroradiological aspects of Joubert syndrome: an analysis of two cases].

PMID- 16281386
TI  - [Reflex epilepsies].

PMID- 16281387
TI  - [Management of status epilepticus].

PMID- 16281388
TI  - [Gender and pain].

PMID- 16281389
TI  - [European action plan on mental health. Facing the challenges, building
      solution].

PMID- 16281390
TI  - [Petr Aleksandrovich Hersten (1871-1947)].

PMID- 16281391
TI  - [Possibilities of endoscopic surgery in treatment of chronic venous insufficiency
      of the lower extremities].
AB  - The authors present their experiences with endoscopic dissection of perforating
      veins in patients with severe forms of chronic venous insufficiency with special
      reference to the peculiarities of blood supply of the extremity superficial
      tissue. The generalized morphological description of the perforating
      arteriovenous structures of the leg is presented as a vascular formation
      including the arteries and veins put in the general connective-tissue vagina and
      beginning from the profound or/and muscular veins and arteries. Operations were
      made on 56 patients aged 25-76 years, 40 of them had postthrombotic disease, 16 -
      varicose disease. The endoscopic subfascial dissection of the perforating veins
      was conducted using the standard set of tools for laparoscopic surgery of K.
      Storz Company. During the surgical procedure the perforating vascular bunch in
      the subfascial space was isolated, the veins were intersected electrosurgically,
      the other parts of the vascular bunch were preserved. On the average, the
      patients were in the hospital for 7+/-2 days. Trophic ulcers healed up during 7
      30 days. Long-term results were good in 30%, satisfactory in 64%, unsatisfactory 
      in 6%. So, the selective endoscopical dissection of perforating veins is thought
      to be a radical, minimally invasive, anatomically and functionally reasonable
      method of elimination of the horizontal venous blood regurgitation. This
      technique resulted in a considerably decreased number of postoperative
      complications and less time of hospital treatment.

PMID- 16281392
TI  - [Bronchopleural fistula--risk factors, prophylactics and treatment in
      oncopulmanology].
AB  - The problem in question is actual because of great incidence of postoperative
      complications and considerable problems with treatment of them. The authors made
      an analysis of surgical treatment of 506 patients with primary cancer and
      carcinoid tumors of the lung. The authors have developed a system of individual
      prognosis of risk of the development of bronchopleural fistulas (BPF), introduced
      an original technique of bronchomyoplasty with the help of m.serratus anterior
      and m.lattissimus dorsi. It resulted in 1.2% less frequency of the development of
      BPF. Current methods and highly informative techniques were used in examining the
      patients. The total number of the examined patients, program and research methods
      allowed reliable conclusions to be obtained.

PMID- 16281393
TI  - [Indications and contraindications to extraperitoneal closing external intestinal
      fistulas].
AB  - Prognostic factors of recurrent external intestinal fistulas after
      extraperitoneal closing them were studied in 74 patients operated on in the
      Sverdlovsk region clinical hospital N1 in 1990-2004. There were no lethal
      outcomes. Good results were noted in 40 out of 74 (54.05%) patients.
      Postoperative complications developed in 34 (45.95%) patients, including 21
      (28.38%) recurrent intestinal fistulas. Using the methods of mathematical
      analysis it was found that the recurrent intestinal fistulas resulted from
      persisting inflammatory alterations in the tissues of the peritoneal and
      intestinal walls and also from appearing due to operation mechanical injuries of
      patency of the intestine canal in the places of suturing the fistulas or the
      initial ones - in the abducent parts of the intestine. The indications and
      contraindications are proposed concerning the using, rational technical means of
      extraperitoneal closing the external intestinal fistulas.

PMID- 16281394
TI  - [Immune correction in patients with colostomas and fistulas].
AB  - Symptoms of secondary immune deficiency were revealed in 37 out of 84 wounded
      with colonic fistulas and colostomas. During the preparation of the patients to
      restorative operations for the improvement of the immune system functions the
      patients were given transfusions of donor leuko-suspension taken from subjects
      with high titer of antibody in blood serum to colon bacillus and intravenous
      infusions of immunoglobulin. Such immunocorrection allowed restoration of immune
      potential of organism during a short time and improvement of the operation
      results.

PMID- 16281395
TI  - [Algorithm of preoperative preparation in surgical treatment of lung echinococcus
      complicated by a rupture into the bronchus].
AB  - The clinical material includes 10 years of observations of 289 patients with lung
      echinococcosis complicated by a rupture into the bronchus. Different operative
      interventions were performed in 278 cases. The indications for operation, their
      volume and preoperative preparation were based on clinico-rentgenological signs
      and divided into 4 groups: 1 - patients with a rentgenological sign of the folded
      chitin membrane, or a ring-shaped shadow; 2 - patients with non-homogeneous
      complicated cysts; 3 - patients with "floating chitin membrane"; 4 patients with
      a rupture of the cyst into the bronchus and pleural cavity simultaneously. The
      third group patients needed more intensive preoperative preparation while the
      fourth group patients had an indication to urgent drainage of the pleural cavity
      or urgent operations in the absence of the purulent discharge from the drains.
      So, the proposed algorithm of the preoperative preparation of lung echinococcosis
      patients complicated by a rupture into the bronchus facilitates the improvement
      of the management of this category of patients.

PMID- 16281396
TI  - [Comparative assessment of the effectiveness of traditional and
      videothoracoscopic thymectomies in complex treatment of myasthenic thymomas].
AB  - A retrospective matched-pair comparison was undertaken to evaluate the surgical
      and neurological outcomes after open and VATS thymectomy for patients with
      myasthenia gravis (MG) and thymoma. Ten women and seven men aged 14-77 years were
      operated upon in St. Petersburg Center of intensive pulmanology and thoracic
      surgery during the years 1995-2002. Results of two groups were compared: 1 -
      operated by VATS (9 patients) and 2 - operated via sterno- or thoracotomy (8
      patients). The first step evaluated the distribution of age, gender, myasthenia
      severity, size, type of thymoma and Masaoka's stage. No difference between the
      groups was found. At the same time, the length of chest tube, blood loss,
      severity of postoperative pains were significantly lower in the first group as
      compared with the second one: 1.3+/-0.9 vs 6.2+/-4.5 days; 82.5+/-22.7 vs 557.1+/
      212 ml; and 1.9+/-0.8 vs 6.1+/-1.2 points respectively. The number of
      postoperative complications was almost the same. All the patients were followed
      up during 24-96 months. There were no thymoma recurrences in the both groups. No
      statistical differences were found in MG course between the groups. A conclusion
      is made that VATS removing of noninvasive thymoma is technically feasible and
      safe for the patients. VATS thymectomy can provide the same results in MG
      treatment as the open approaches.

PMID- 16281397
TI  - [Specific features of diagnosis of hormonal insufficiency in patients with tumors
      of the adrenal cortex].
AB  - An examination of 145 patients with incidentalomas and 195 women with virale
      syndrome has shown that 20% of patients with incidentalomas and 23.1% of patients
      with steroidogenesis have disorders of the adrenal steroidogenesis characteristic
      of the obliterated form of congenital hyperplasia of the adrenal cortex (CHAC)
      with a defect of 11beta-hydroxylase on the basis of the following biochemical
      criteria: the elevation in blood of the basal levels of 11-desoxycortisole and
      11beta-desoxycorticosterone, decreased excretion of free cortisole with urine,
      lower indices of hydrocortisole/cortisone in blood and free cortisole/free
      cortisone in urine, in the test with corticotropin - elevation in blood of the
      level of 11-desoxycortisole and 11-desoxycorticosterone, decreased relationships
      cortisole/11-desoxycortisole and cortisole/cortisone and lower growth of the
      levels of corticosterone and cortisole. The data obtained suggest that long
      standing obliterated form of CHAC with a defect of 11beta-hydroxylase might be
      the cause of the formation of certain incidentalomas.

PMID- 16281398
TI  - [A technique of videothoracoscopic thymectomy in diseases of the thymus].
AB  - Intensive development of thoracoscopic thymectomy (Tthy) has been initiated
      during the last decade. Unfortunately very few instances of using the procedures
      have been described in Russian medical literature. So, the paper describes in
      detail the technique and results obtained in our clinic. At the period from 1998
      through 2004 37 Tthy operations were performed in the St. Petersburg Center of
      intensive pulmonology and thoracic surgery. There were 21 female and 15 male
      patients with mean age 41.5+/-18.9 years. Myasthenia gravis (MG) was diagnosed in
      19 of those patients. Different thoracoscopic approaches were used for Tthy: 20
      from the right side, 15 from the left side and 2 combined approaches with neck
      incision. In 2 cases when invasive thymoma was suspected, sternotomy had to be
      used. There were 6 postoperative complications (1 haemothorax and 5 myasthenia
      cases). One patient died in 45 days after operation because of the ventilation
      associated pneumonia. The results of treatment were followed up in 34 patients
      during 6-34 months. The MG course was followed up in 17 out of 19 patients, 9
      (52.9%) being asymptomatic, 6 (35.3%) improved and 2 (11.8%) stable. Tthy is a
      novel technical possibility for a removal of the thymus gland. The procedure is
      quite safe and radical in the hand of a surgeon experienced in mediastinal and
      thoracoscopic surgery. Treatment of thymoma using Tthy requires meticulous
      technique and longer follow-up.

PMID- 16281399
TI  - [Actual questions of endocrinous surgery: a viewpoint of a participant of
      international congresses in 2003-2004].

PMID- 16281400
TI  - [The history of surgery of the thyroid gland].

PMID- 16281401
TI  - [Comparative aspects of the methods of diagnosis of soft tissue injuries in
      traumas of the talocrural articulation].
AB  - The authors give grounds for using effective methods of diagnosis of injuries of
      the talocrural articulation in clinical practice. The role of MRT, USI,
      thermometry are presented in a comparative aspect. The diagnostic means of
      traditional X-ray examinations are also shown. It was found that thermometry in
      complex with X ray methods of diagnosis and USI systematized the diagnostic
      information, allowed corrections of medical programs, determined the time of the
      end of restoration of injured elements of the talocrural articulation with
      special reference to each patient.

PMID- 16281402
TI  - [Aggregation state of blood and the significance of its impairments in bleedings
      of portal genesis].
AB  - Account of such indices of blood rheology as viscosity, erythrocyte aggregation
      coefficient, indices of lipid peroxidation and endogenous intoxication allowed
      the authors to fulfill therapeutic treatment of patients with hemorrhage of
      portal genesis more efficiently.

PMID- 16281403
TI  - [Immediate results of pneumonectomies in lung cancer patients older than 70
      years].
AB  - During 1970-2002 pneumonectomy for lung cancer was fulfilled on 155 patients
      older than 70 years of age. Immediate postoperative lethality took place in
      19.3%. From 142 male patients after pneumonectomy 30 (21.1%) patients died, from
      13 female patients - nobody died. The whole time was divided into 3 periods 10
      years each. It was noted that postoperative lethality decreased from 21.4% in the
      first period to 13.8% - in the third one. Lethality was substantially decreased
      in patients aged 70-72 from 32.6% in 1970-1981 to 6.9% in 1992-2002. In patients
      older than 75 lethality failed to decrease. The main causes of lethal outcomes
      were acute cardio-vascular insufficiency and thromboembolism of the pulmonary
      artery.

PMID- 16281404
TI  - [Endarterectomy from the distal arterial bed in prosthetics of the aorta and
      iliac arteries].
AB  - The work presents an experience with surgical treatment of 32 patients with
      critical ischemia of the lower extremities developed against the background of
      two-levels occlusive lesion of the arterial bed of the lower extremities. All the
      patients had atherosclerosis. Occlusion of the abdominal part of the aorta was
      the cause of reconstruction of the aorta and iliac arteries in 15 patients,
      occlusion of the iliac artery - in 14 patients, aneurysm of the abdominal aorta -
      in 3 patients. In all the patients the proximal lesion was associated with
      occlusion of the femoral arteries. In addition to proximal reconstruction,
      retrograde endarterectomy was made with a special instrument from the femoral
      arteries through the arteriotomy opening intended for distal anastomosis of a
      synthetic prosthesis. Complete revascularisation of the arterial bed of the lower
      extremities was obtained in all the patients. There were no lethal outcomes.

PMID- 16281405
TI  - [Acute hemorrhoidal thrombosis: essence of the idea, correctness of the name and
      unification of terminology. alternative approaches to treatment].
AB  - Acute thrombosis of hemorrhoidal nodes (ATHN) was treated in 402 patients aged
      from 19 through 73 years of age. It was found that the decision for the volume
      and method of treatment should be determined individually and differentially,
      paying special attention to the degree of microcirculatory alterations in the
      walls of cavernous veins. Multi-component conservative therapy is the method of
      choice for treatment of ATHN of the 1st severity degree. For the II and III
      degree operation is indicated which should be fulfilled urgently (within 3 days)
      or in a postponed (within 5-7 days) order. Hemorrhoidectomy by Milligan-Morgan
      method with the tight suturing of the postoperative wounds and complete
      restoration of the mucous membrane of the anal canal allowed getting better
      immediate and long-term results.

PMID- 16281406
TI  - [Effectiveness of hernioplasty with using a polypropylene mesh implant in
      treatment of postoperative ventral hernias].
AB  - A new method of operative treatment of postoperative ventral hernias is proposed
      which provides reliable fixation of the implant along the whole line of the
      primary scar. It excludes its migration due to profound integration into all
      layers of the abdominal wall and reliable fixation at different levels and with
      sufficient distance from the hernia hilus. The method can be used for any size of
      the hernia hilus. This method of plasty of the anterior abdominal wall is
      especially indicated for great, inreducible hernias, for great defects of the
      abdominal wall and incarcerated postoperative hernias when continuous
      preoperative preparation is impossible. Long-term results of the operative
      treatment were analyzed in terms from 1 year to 3 years in 16 patients aged from
      40 to 73 years of age (mean age 58+/-2.6 years) with great and giant
      postoperative hernias. No recurrences were noted.

PMID- 16281407
TI  - [Foreign bodies in surgeon's practice].

PMID- 16281408
TI  - [A case of successful treatment of severe acute surgical sepsis].

PMID- 16281409
TI  - [Multiple iatrogenic foreign bodies in the small intestine].

PMID- 16281410
TI  - [An organismoid teratoma of the abdominal cavity in a 7 year old child].

PMID- 16281411
TI  - [Erast Gavrilovich Salishchev--an outstanding pedagogue of the higher school
      (1851-1901)].

PMID- 16281412
TI  - [The role of changes of the perforating veins in the development of chronic
      venous insufficiency of lower extremities].

PMID- 16281413
TI  - [The present-day features of surgical infection].

PMID- 16281414
TI  - [Surgical treatment of lung cancer in elderly patients].

PMID- 16281415
TI  - [Academic Medicine today].

PMID- 16281416
TI  - [Long duration of hospital stay in a clinical service].
AB  - In order to identify determining factors and complications in illness, we
      evaluated patients under long period hospitalization, in a Clinical Service.
      METHODS: retrospective and descriptive studies. Figures were evaluated by Chi-,
      Fisher T and Test T, thrue variables. We call long period hospitalization to a
      staying of 10 days or longer. RESULTS: 322 patients were evaluated. 50 (15,5%)
      presented (LS) and 272 < 10 days staying. Age average was 63,8 for < 10 days and
      66 for (LS). Mostly of diagnosis at admission for < 10 days were respiratory
      dysfunction (25%) including pneumonia (10%), urinary infection and heart failure,
      and for LS pneumonia 20%, acute neurological disease 18 %. The 46 % of LS
      required surgery vs. 20,6% (p < 1,01). The LS needed parenteral nutrition 26 %
      vs. 12,5% (p < 0,02). The average of maximum amount of drugs/day in staying was:
      5,8 for < 10 days and 8,76 for LS (p < 0,01). Hospital complications in LS were
      28 % vs. 11% (p < 0,01), mainly nosocomial pneumonia (p < 0,01) and endovascular
      infections (p < 0,01). Staying in ICU was 54% for LS vs. 19% (p < 0,01), and
      average of days in intensive care unit (ICU) was 8 in LS vs. 3 (p < 0,01). There
      wasn't any difference in mortality. CONCLUSION: the admission's diagnosis and the
      ICU's staying were the main causes of LS, but not so age and co-morbilities
      studied. The LS patients require more complex and expensive staying. They present
      more hospital complications.

PMID- 16281417
TI  - [Drug monitoring in hospitals of Cordoba City (Argentina). 2-year-experience of
      the Pharmacological Department as a peripheric effect of ANMAT].
AB  - There were designed Monitorings study (FVG), centred on three Public Hospitals of
      C6rdoba, seeking to detect Adverse Reactions for medicines. To such purpose there
      were realized forming courses of human resources in FVG. FVG's cards were
      distributed, of own design, recovered then. For statistical calculation there was
      applied the INFO 4. 84 informed cards were recovered. The groups of involved
      medicines: they were: Antibiotics (22%), cardiovascular (16%), antiulcerous
      (10%), anxiolytics (8.75%), nonsteroidal anti-inflammatory (8%), onchologics
      (6%), anticonvulsants (3.75%), hypolypemics (3.5%), sexual hormones (2.5%),
      hypoglycemics (2.5%), plasmatic expansors (2.5%). The organs affected by RAM
      were: Central Nervous System (25%), skin (25%), gastrointestinal (17.5%), Bleeds
      (7.5%), cardiovascular (7.5%), respiratory (7%), immune (6%), renal (4%). The
      analysis of imputability indicated: Definite RAM: 10 % Probable RAM: 90%.

PMID- 16281418
TI  - [Hyperhomocysteine like thrombocytic risk factor in patient with systemic lupus
      erythematous with antiphospholipid syndrome].
AB  - OBJECTIVES: to detect the prevalence of hyperhcy in SLE patients with and without
      antiphospholipid syndrom; to compare the Hcy levels between those patients and
      healthy controls and to determine the correlation between hyperhcy and
      antiphospholipid antibodies. PATIENTS AND METHODS: we studied 44 SLE patients: 17
      had antiphospholipid syndrom and 27 didn't have it, and we compared them to 24
      healthy controls. All of them where checked clinically and with laboratory tests
      like anticardiolypin antibodies, lupus anticoagulant and Hcy. Hcy > 9 was
      considered abnormal. Patient who had hyperhcy were treated with folic
      acid+vitB6+vitB12 a month along. STATISTICAL ANALYSIS: cualytative variables: chi
      square or Fischer's; cuantitative variables: Student's T test or Mann-Whitney's
      test. RESULTS AND CONCLUSIONS: there were 35 trombotic manifestations in 44
      patients. Hyperhcy was present in 27 SLE patients (61,4%), 12 of them had
      antiphospholipid syndrom. Hcy concentrations patients vs.controls was
      statisticaly different (p=0,002). There was also stastisticaly different the hcy
      concentration from SLE patients with SAF vs controls (p=0,003) and without SAF vs
      controls (p= 0,015). From 33 SLE patients, 20 (33%) were aCL(+). 15(75%) of them
      had hiperhcy.

PMID- 16281419
TI  - [Maternal mortality. A necessary revision for its acknowledgement, its medical
      and social causes and a proposal of actions to be undertaken for its reduction].
AB  - Maternal mortality is a portrait not only related to maternal health and to the
      characteristic of the medical services, but also to the social, cultural and
      political conditions of a given society. It occurs 120 billons pregnancy every
      year and almost 600.000 women die because of causes related to pregnancy,
      delivery or puerperal diseases, 95% of those deaths occur in underdeveloped
      countries. In Swiss, Finland, Canada and Holland, 4 deaths are registered, while
      in Somalia and Nigeria 1000 death are reported for each 100.000 alive new baby
      (NV), Meanwhile, in Latin America and the Caribe, 190 death are reported, almost
      23.000 women death every year, which clearly shows a great difference between
      countries. These differences also occur within a given country, as in Argentina,
      where the prevalence is 44 for each 100.000 NV, Buenos Aires has 9 while Formosa
      as 177. We pointed out that nonqualified medical services is a very important
      fact on the above mentioned maternal death, because of the lack of attention of
      the sepsis, the hemorrahages, the prolonged delivery work and the eclampsia. But
      abortion is the most important cause of maternal death. We mentioned the social,
      educational and sanitary facts of illegal abortion. In developed countries pre
      eclampsia is the main factor. It is mentioned the strategies of the International
      Conference "Maternity without Risk" carried out in Nairobi in 1987 and the Task
      Force Inter Regional Agency for the Reduction of Maternal Mortality. 2004 as a
      good recommendation to be taken into account in order to diminish maternal
      mortality. We propose to highlight the use of the Maternal Mortality Committee
      and the application of the Epidemiological Survey System, in order to diminish
      maternal mortality and some particular ones for the prevalent pathologies and it
      is concluded that maternal mortality could diminish not only with better sanitary
      conditions, but also with equal social conditions, specially in underdeveloped,
      countries where this situation is a real problem.

PMID- 16281420
TI  - [Admission to medical education at the School of Medical Sciences of the National
      University of La Plata: its effectiveness].
AB  - BACKGROUND: The present paper, based on studies carried out as from the year 1972
      at the Department of Anatomy "C" of the Medical Sciences School of the National
      University of La Plata, analyzes the performance of students who entered the
      aforementioned School with and without entrance examination. OBJECTIVES: To
      evaluate the performance achieved by the students, considering for the analysis a
      cross section of two groups, those who entered the School between the years 1985
      and 1988 and those who did it between 1992 and 1999, without and with entrance
      examination respectively. MATERIALS AND METHODS: The following variables were
      evaluated: Dropout average percentage. Average percentage of students who passed
      in November, December and March. Average percentage of students who passed the
      mid-term tests. Mid-term tests average mark. The performance records of each
      student in the department were audited: personal information, assistance, mid
      term tests marks, homework, familiarity with topic of the day, interest in the
      practical activity and student overall impression. The statistical analysis
      evaluated whether there were any particular differences between the groups
      compared. RESULTS: Dropout average percentage: without admissibility*: 27,15%,
      with admissibility: 7,91% Average percentage of students who passed in November,
      December and March: without admissibility: 50,75%, with admissibility: 90,43%
      Average percentage of students who passed the mid-term tests: without
      admissibility: 68,75%, with admissibility: 93,29% Mid-term tests average mark:
      without admissibility: 6,63%, with admissibility: 6,86% *Admissibility = entrance
      examination CONCLUSIONS: The overall performance of the students with entrance
      selection surpasses the one of those who entered directly.

PMID- 16281421
TI  - [Forgetfulness of the histology curriculum in medical students].
AB  - MEMORY: ability to record, file, classify and later recover of information.,
      essential in processing information and learning, in analogy with a computer.
      FORGETFULNESS: failure to transfer information from short term memory to long
      term memory or to recover information from the latter. AIM: to study
      forgetfulness in contents of Histology in students one and half year after
      regular course. To evaluate level of re-utilization of contents in second and
      third year courses. Students with high performance in 2002 (n=26) were evaluated
      with 20 cytology and histology questions and 20 questions related to organs. 20
      multiple choice and 20 brief filled answers were used, expressing the level of
      usefulness of the contents in Physiology and Physicochemistry, and in the first
      quarter of Pathology, Microbiology and Pharmacology. The performance of 2002
      course was compared with the current test, results of cytology and histology
      questions versus organs ones and multiple choice answers versus brief filled
      answers. The loss was in the order of 50% in the recovery of contents (37.07 +/-
      1,76 = 92,6% vs. 18,52 +/- 4,33 = 46,3%) without difference between cytology and
      histology versus organs neither among multiple choice answers versus brief filled
      answers. The highest usefulness in the contents refers to Pathology (69%) and
      Physiology (50%) and the lesser to PhysicoChemistry.(7%) We estimate that
      forgetfulness in our students would have been even higher without the employment
      of active techniques of learning.

PMID- 16281422
TI  - [Chronology and current status of the therapy in acute pancreatitis].
AB  - This article realize a retrospective analysis of the course of acute pancreatitis
      and evidence changes of concepts upon physiopathogenesis aspects, the natural
      history of the disease and the therapeutic management. The responsability of the
      biliary factor its accepted but the classic mechanism of the biliopancreatic
      reflux by common chanel its on discussion. Relativeness to natural history of the
      acute pancreatitis, however of to remain un known sone aspects to ellucidate on
      the future, today its accepted the biphasic course of the severe pancreatitis,
      with one initial period and other tardif, to second or their week, with septic
      complications or evolution to resolution of process. The concept of systemic
      inflammatory response syndrome and failure of organ systems (renal insufficiency,
      pulmonary insufficiency) its essential for interpretation of the ominous
      consequences of one inopportune surgical approach on the early period, associated
      with high mortality. One schematic personnel square present the different
      therapeutics procedures along the years, from the distant and dogmatic surgery
      for principle, until the actual moment where the conservative attitude its of
      unanimous acquiescence on critic period of disease. The surgery its indicated on
      second phase, with developing of septic complications, reactivation or
      persistence of systemic inflammatory response syndrome with increasing severity
      of pancreatitis.

PMID- 16281423
TI  - [Evidence based medicine].
AB  - Evidence based medicine is a systematic method employed to secure the best
      scientific available evidence when making clinical decisions. Several steps are
      taken in these process, describing a clinical scenario, formulating a specific
      clinical question, searching the literature for the pertinent studies, selecting
      the relevant articles using rules of evidence, understanding and calculating
      measures of effect, and finally incorporating the evidence and patients
      preferences in the clinical decision process.

PMID- 16281424
TI  - FDA introductory comments: clinical studies design and evaluation issues.

PMID- 16281425
TI  - How FDA currently makes decisions on clinical studies.

PMID- 16281426
TI  - Introduction to Bayesian methods I: measuring the strength of evidence.
AB  - Bayesian inference is a formal method to combine evidence external to a study,
      represented by a prior probability curve, with the evidence generated by the
      study, represented by a likelihood function. Because Bayes theorem provides a
      proper way to measure and to combine study evidence, Bayesian methods can be
      viewed as a calculus of evidence, not just belief. In this introduction, we
      explore the properties and consequences of using the Bayesian measure of
      evidence, the Bayes factor (in its simplest form, the likelihood ratio). The
      Bayes factor compares the relative support given to two hypotheses by the data,
      in contrast to the P-value, which is calculated with reference only to the null
      hypothesis. This comparative property of the Bayes factor, combined with the need
      to explicitly predefine the alternative hypothesis, produces a different
      assessment of the strength of evidence against the null hypothesis than does the
      P-value, and it gives Bayesian procedures attractive frequency properties.
      However, the most important contribution of Bayesian methods is the way in which
      they affect both who participates in a scientific dialogue, and what is
      discussed. With the emphasis moved from "error rates" to evidence, content
      experts have an opportunity for their input to be meaningfully incorporated,
      making it easier for regulatory decisions to be made correctly.

PMID- 16281427
TI  - Introduction to Bayesian methods II: fundamental concepts.
AB  - The use of Bayesian design and analysis is burgeoning. In this introduction to
      Bayesian methods, we provide basic examples of Bayesian thinking and formalism on
      which more complicated and comprehensive approaches are built. These include
      adjusting estimates using related information, the use of Bayes theorem in
      diagnostic testing, the relationship of the prior and posterior distributions for
      situations where both the data and prior distribution are Gaussian, and the key
      steps in a Bayesian analysis. If Bayesian methods are carefully developed and
      applied, they have excellent objective (i.e., frequentist) properties, providing
      marvelous tools to help improve the FDA regulatory process.

PMID- 16281428
TI  - Introduction to Bayesian methods III: use and interpretation of Bayesian tools in
      design and analysis.
AB  - The Bayesian approach and several of its advantages in drug and medical device
      development are described. One advantage from the perspective of analysis is that
      it provides a methodology for synthesizing information. However, taking a
      Bayesian approach to designing clinical trials is potentially more valuable than
      using this approach in analyzing trial results. Bayesian methodology provides a
      mechanism for updating what is known as results accumulate during a trial. Such
      updating can be incorporated completely explicitly and prospectively. An
      important way in which the Bayesian approach can be used is in calculating the
      predictive probability distribution of future results on the basis of current
      results. I show how to exploit predictive distributions in adapting to results
      that accumulate during the course of a trial. Possible adaptations including
      decreasing or increasing sample size, dropping treatment arms, and modifying the
      randomization proportions to the various arms depending on the interim results.
      Consequences of taking a Bayesian approach to clinical trial design are
      efficiency, better treatment of patients in the trial, and greater precision
      regarding the primary endpoints. An example of the last of these is Bayesian
      modeling of the relationship between early and longer term endpoints. Such
      modeling also enables earlier decision making. Case studies 2 and 3 deal with
      trials that were shorter and smaller, respectively, because of such modeling.

PMID- 16281429
TI  - A Bayesian approach to randomized controlled trials in children utilizing
      information from adults: the case of Guillain-Barre syndrome.
AB  - BACKGROUND: Guillain-Barre syndrome (GBS) is a rare neurologic disease that
      occurs at all ages, causing a progressive, ascending paralysis that usually
      resolves over weeks or months. The disease appears to be identical in children
      and adults, except that children recover more quickly, with fewer residua. For
      patients who lose the ability to walk independently, the main treatment options
      are plasmapheresis or intravenous immune globulin (IVIg), treatments that have
      shown to have identical effectiveness in adults in two large RCTs involving 388
      patients. The effectiveness of the treatments in children has only been studied
      in small, poorly controlled studies. If one could capture all eligible patients
      in the United States, only about 100-300 children would be available for a trial
      annually. METHODS: The goal of this case was to demonstrate how Bayesian methods
      could be used to incorporate prior information on treatment efficacy from adults
      to design a randomized noninferiority trial of IVIg versus plasmapheresis in
      children. A Bayesian normal-normal model on the hazard ratio of time to
      independent walking was implemented. RESULTS: An evidence-based prior was
      constructed that was equivalent to 72 children showing exact equivalence between
      the therapies. A design was constructed based on a Bayesian normal-normal model
      on the hazard ratio, yielding a sample size of 160 children, with a preposterior
      analysis demonstrating a "Type I" error rate of 5% and a power of 77%.
      CONCLUSIONS: This case study illustrates a rational approach to constructing an
      evidence-based prior that would allow information from adults to formally augment
      data from children to minimize unnecessary pediatric experimentation. The
      frequentist properties of a Bayesian design can be evaluated and reported as they
      would be for a standard design. Discussion of the appropriate prior for such
      designs is both a necessary and desirable feature of Bayesian trials.

PMID- 16281430
TI  - Using prior distributions to synthesize historical evidence: comments on the
      Goodman-Sladky case study of IVIg in Guillain-Barre syndrome.
AB  - One feature of the Bayesian approach is that it provides methods for synthesizing
      what is known about a question of interest and provides a formalism based on the
      laws of probability for incorporating this auxiliary knowledge into the planning
      and the analysis of the next study. In this comment, we use elements of the
      Goodman-Sladky case study to illustrate (1) the use of Bayesian methods to
      quantify historical information about an intervention through the specification
      of a prior distribution, (2) an approach to the analysis of the sensitivity of
      the conclusions of a Bayesian analysis to the specification of the prior
      distribution, and (3) we comment on the role of research synthesis for combining
      information about an intervention from different data sources as a tool to help
      summarize evidence about the intervention.

PMID- 16281431
TI  - Bayesian predictions of final outcomes: regulatory approval of a spinal implant.
AB  - We describe a randomized controlled trial of an investigational spinal implant.
      The investigational device has an obvious benefit in comparison with control in
      that it precludes the need for harvesting bone graft and the pain and morbidity
      associated with it. Therefore, the principal comparison is one of noninferiority.
      The primary endpoint is overall success at two years. The "noninferiority margin"
      is 10%. Waiting for two years after the last patient's surgery may not be
      necessary depending on earlier measurements of success. We model the relationship
      between one- and two-year results. Our Bayesian analysis considers all available
      information, including some patients who have both one- and two-year results and
      some patients who have only one-year results. Our study provides an example in
      which Bayesian predictive modeling provided earlier information than otherwise
      and therefore it shortened the time line of the development of a therapeutic
      strategy.

PMID- 16281432
TI  - ASTIN: a Bayesian adaptive dose-response trial in acute stroke.
AB  - Understanding the dose-response is critical for successful drug development. We
      describe an adaptive design to efficiently learn about the dose-response and the
      ED95. A dynamic termination rule allows for early discontinuation either for
      efficacy or futility. The design was deployed in ASTIN, a phase II proof-of
      concept trial of the neuroprotectant, neutrophil inhibitory factor (NIF), in
      acute stroke. We discuss the learning from this trial.

PMID- 16281433
TI  - The experience in the FDA's Center for Devices and Radiological Health with
      Bayesian strategies.

PMID- 16281434
TI  - Enhanced physiotherapy management of acute exacerbations of chronic obstructive
      pulmonary disease.

PMID- 16281435
TI  - Barriers to success for an evidence-based guideline for chronic obstructive
      pulmonary disease.
AB  - OBJECTIVES: To evaluate 1) barriers to clinical guideline use and 2) the
      relationship between guideline use and inpatient outcomes in chronic obstructive
      pulmonary disease (COPD). METHODS: 1) Four focus groups of specific health
      professions (n = 30), from three metropolitan hospitals, and interview of 99
      medical officers (MOs), linked to 349 admissions, both guided by behavioural
      modelling theory; 2) association between guideline use and patient outcomes
      (length of hospital stay > or = 14 days, and readmission within 28 or 90 days)
      was evaluated in a cohort of 405 COPD patients. RESULTS: 1) In focus groups,
      nurses and allied health professionals emphasized facilitation issues including
      paperwork duplication and time limitations as barriers, but considered improved
      patient care outcomes as the major guideline use determinant. There were similar
      findings in junior MOs (nonconsultants) by both focus group and interview, with
      the addition of a need for a sense of ownership. Senior MOs (consultants) greatly
      emphasized sense of ownership. Barriers to guideline use varied between types of
      units. Behavioural modelling explained 49% of the variation in intention to use
      the guideline for MOs. For nonconsultants, habit and intention were significantly
      associated with extent of guideline use. 2) Patient outcomes: guideline use was
      not associated with length of stay or readmission. CONCLUSIONS: 1) Guideline
      implementation should address issues relevant to different health professions,
      units and seniority of profession. 2) Guideline use was not associated with
      reductions in readmission or length of stay.

PMID- 16281436
TI  - Factors associated with reduced FEV1 in adult patients with cystic fibrosis in a
      relatively affluent area.
AB  - Data collected on adult cystic fibrosis (CF) patients and entered onto the CF
      database in the south and west regions of England were analysed for the year
      2001. FEV1 was taken as a marker of lung disease severity. Data on 371 patients
      (158 female) mean age 24.7 years (range 16.0-48.9) were assessed. FEV1 was
      reduced in CF patients infected with Pseudomonas aeruginosa (Pa) (mean 62.6%
      predicted) compared with those without (mean FEV1 77.8%, P < 0.00001). The
      reduction was noted irrespective of age group. FEV1 progressively reduced with
      the increasing need for high-intensity treatment (P < 0.00001) and with the
      diagnosis of diabetes mellitus (P = 0.03). FEV1 correlated with body mass index
      (BMI) (r = + 0.42, P < 0.0001). Genetic profile and poverty and deprivation score
      did not affect the value of FEV1. Chronic infection with Pa mainly in young
      adults, treatment intensity, diabetes mellitus and reduced body mass index are
      associated with reduced FEV1 in adult patients with cystic fibrosis in the south
      and west regions of England. In this relatively affluent area, scores of poverty
      and deprivation were not associated with the decline in lung function tests.

PMID- 16281437
TI  - Physiotherapy management of cystic fibrosis.
AB  - For many years physiotherapy for cystic fibrosis (CF) was synonymous with a daily
      routine of postural drainage and percussion. Improved longevity and a desire for
      independence, together with a clearer understanding of the pathophysiology of the
      disease, has led to the development of many airway clearance techniques. The
      contribution of 'chest' physiotherapy remained unchallenged until recent times
      when lack of robust evidence and the presentation of asymptomic infants and
      adults led some physiotherapists to question this traditional approach. As
      survival increases into the fourth and fifth decade unique complications have
      evolved and physiotherapy management is challenged with nonrespiratory aspects of
      treatment. This review will consider the evidence for, and current practice of
      airway clearance, the value of exercise and the emerging problems of
      musculoskeletal complications and incontinence.

PMID- 16281438
TI  - Management of the chronically ventilated patient with a tracheostomy.
AB  - Tracheostomy is the most common surgical procedure performed on critically ill
      patients. For those who survive their critical illnesses but remain ventilator
      dependent, tracheostomy provides patients with a secure airway that frees the
      mouth for oral nutrition, enhances verbalized speech, and promotes generalized
      comfort. Avoiding complications from tracheostomy requires a skilled multi
      disciplinary approach to ensure that the benefits outweigh the risks of the
      procedure.

PMID- 16281439
TI  - Exhaled nitric oxide in paediatric asthma.
AB  - Assessment of airway function is difficult in young children with asthma, and in
      addition, only reflects the status of the disease at the time of the measurement.
      Thus, there is increasing interest in monitoring airway inflammation in asthma,
      which may provide a longer term assessment of disease activity. Most methods of
      assessing asthmatic inflammation are invasive, and are not feasible in the
      paediatric population. This review discusses exhaled nitric oxide as a marker of
      asthmatic inflammation, and compares it with other recognized markers. Exhaled
      nitric oxide has the potential to become a noninvasive method of assessing asthma
      control in the paediatric population.

PMID- 16281440
TI  - [Cooling off...the cold, really?].

PMID- 16281441
TI  - [Primary HIV infection: an update].
AB  - Acute HIV infection is a frequently symptomatic event. Presenting as a
      mononucleosis-like disease with fever, lymphadenopathy, myalgias, rash and
      headache, it is insufficiently identified. Since acute HIV infection is
      associated with high viral loads it is important to diagnose patients with this
      entity, in order to prevent transmission. An evolution towards AIDS can happen
      more rapidly according to length and severity of the symptoms, but it is still
      controversial whether very early therapy during acute seroconversion is
      beneficial on the long-run. Randomised controlled trials of early short-term
      antiretroviral treatment versus deferred therapy are both ethically justifiable
      and necessary.

PMID- 16281442
TI  - [Swiss recommendations for the management of gential herpers and herpes simplex
      virus infection of the neonate].
AB  - Genital herpes is being recognised as a medical problem of increasing importance.
      Diagnosis and management are complex. The present recommendations have been
      established by a multidisciplinary panel of specialists and endorsed by all Swiss
      medical societies involved in the medical care of such patients. The aim is to
      improve the care of affected patients, to reduce horizontal and vertical
      transmission and to diminish the psychosocial burden.

PMID- 16281443
TI  - [Occupational exposures with risk of transmission of HIV, HBC and HCV in health
      care workers].
AB  - Health care workers are often victims of occupational injuries by contaminated
      sharps or projection of contaminated fluids to mucous membranes and are therefore
      at risk for transmission of HIV, HBV and HCV. Every technical and organisation
      related measure useful to prevent injuries should be implemented and personal
      protection equipment must be made available to workers. Promotion of hepatitis B
      immunization is a key issue. Immediate evaluation of injured employee is
      necessary to assess the risk related to exposure and the indication for post
      exposure prophylaxis (anti-retroviral therapy for HIV, immunoglobulins and
      vaccination for hepatitis B). When a health care worker has been exposed to one
      of the blood-born viruses, thorough information and follow-up should be offered
      by a specialist.

PMID- 16281444
TI  - [Community-acquired pneumonia: attitude case of treatment failure].
AB  - It can be determined that for nearly one out of five patients hospitalized for a
      community-acquired pneumonia the empirical treatment chosen will fail. Those for
      whom the treatment failed face a bad outcome with a mortality rate as a high as
      43%. Most causes of failure can be attributable to the patient rather than to the
      antibiotic or to the pathogen. The studies related to treatment failure show that
      resistance of the causal agent to antibiotic is rarely the cause, as opposed to
      discordant therapy (causal agent not covered by chosen antibiotherapy), which
      plays an important role. In these studies the multivariate analysis were able to
      show that concordant therapy (causal agent covered by chosen antibiotherapy),
      vaccination against influenza, monocytosis and old age were possible protective
      factors against treatment failure.

PMID- 16281445
TI  - [Positive blood cultures during a 2 years period at Hospital cantonal de
      Fribourg].
AB  - Several authors, mainly from the United States, have reported on the microbiology
      and interpretation of positive blood cultures. We conducted a retrospective study
      over a 2 years period to address this issue in a medium-size swiss hospital: two
      hundred and thirty-two episodes of positive blood culture were recorded, with 403
      microorganisms; Escherichia coli (22%), Staphylococcus aureus (21%) and coagulase
      negative staphylococci (110%) were the most frequent isolates. The latter were
      considered as contaminants in 38% of cases. Half the episodes were nosocomial,
      23% originated from the urinary tract and 18% were linked to a vascular catheter.
      Attributable mortality of bacteremia/fungemia was 9%, significantly higher for
      fungi (36%) than for bacteria (8%; p 0.009).

PMID- 16281447
TI  - [Fulminant smoking in smoke].

PMID- 16281446
TI  - [Blood culture negative endocarditis: a diagnostic challenge].
AB  - Blood culture negative endocarditis (BCNE) account for about 5% of all cases of
      endocarditis. Diagnosis and initiation of antimicrobial therapy may be delayed,
      with a negative impact on clinical outcome. The most common cause of BCNE is
      antimicrobial drug therapy before blood sampling. Other common causes include
      slow growing and non cultivable organisms. Identification of the etiologic agent
      is critical in the management of BCNE and molecular tools such as broad range
      16SrRNA PCR technique followed by direct automated sequencing and microorganism
      specific PCR are promising. Some authors have proposed to include these
      techniques among major Duke's criteria for the diagnosis of BCNE.

PMID- 16281448
TI  - [Geneva, 1820-1836: the iodine affair].

PMID- 16281449
TI  - [Science without conscience is not the ruin of the soul].

PMID- 16281450
TI  - [Behavior disorders in children and adolescents: what is the responsibility of
      medicine?].

PMID- 16281451
TI  - [Avian influenza, the new menace that hangs over our heaven (6)].

PMID- 16281452
TI  - [The Nobel prize for medicine 2005 goes to two Australians who revolutionized the
      treatment of gastroduodenal ulcer].

PMID- 16281453
TI  - [Some "definitive" responses to the Chernobyl nuclear disaster].

PMID- 16281454
TI  - [In what can we believe in again?].

PMID- 16281455
TI  - Regulation of Sertoli cell and germ cell differentation.
AB  - Unwanted childlessness affects approximately one in six couples worldwide.
      According to the World Health Organization, in nearly 40% of cases the cause can
      be attributed to the female, in 20% to the male, in 25% to both, and in 15% the
      cause remains unknown. The incidence of male factor infertility in the general
      population is approximately 7%. The majority of these men experience irreversible
      idiopathic infertility and cannot father children without some form of medical
      intervention. Male factor infertility, in addition, may be caused by testicular
      germ cell cancer, which is known to represent the most common cancer among young
      men in Western industrialized countries. There is growing evidence that this
      cancer originates from fetal germ cells exhibiting an aberrant programme of gene
      expression and that tumour progression may be favoured by an aberrant Sertoli
      cell-germ cell communication. The present monograph aims to shed more light on
      the regulation of Sertoli and germ cell differentiation. Involving knockout and
      transgenic mouse models, the authors focus on (a) male factor infertility that
      might be related to altered maturation of Sertoli cells, (b) male factor
      infertility that might be due to incorrect histone-to-protamine exchange in
      haploid spermatids, and (c) progression of testicular germ cell cancer that might
      be favoured by an aberrant Sertoli cell-germ cell communication.

PMID- 16281456
TI  - Lessons learned from the 1954 Field Trial of Poliomyelitis Vaccine.

PMID- 16281457
TI  - Monitoring data on data monitoring.

PMID- 16281458
TI  - Dynamic treatment regimes: practical design considerations.
AB  - BACKGROUND: Clinical management of chronic disease requires a dynamic treatment
      regime (DTR): rules for choosing the new treatment based on the history of
      response to past treatments. Estimating and comparing the effects of DTRs from a
      sample of observed trajectories of treatment and outcome depends on the
      untestable assumption that new treatments are assigned independently of potential
      future responses to treatment, conditional on the history of treatments and
      response to date ("sequential ignorability"). In longitudinal observational
      studies, sequential ignorability must be assumed, while randomization of dynamic
      regimes can guarantee it. METHODS: Using several clinical examples, we describe
      the simplest randomized experimental designs for comparing DTRs. We begin by
      considering an initial treatment A and a second treatment B, and discuss how a
      dynamic treatment regime that starts with A and leads (sometimes) to B, might be
      compared to either fixed treatment A or B. We also illustrate the problem of
      finding the optimal sequence of treatments in a DTR, when there are several
      choices. We describe and contrast two ways of incorporating randomization into
      studies to compare such regimes: baseline randomization among DTRs versus
      randomization at the decision points (sequentially randomized designs).
      CONCLUSIONS: We discuss estimation and inference from both baseline randomized
      and sequentially randomized designs and conclude with a discussion of the
      differences between the experimental and observational approaches to optimizing
      and comparing dynamic treatment regimes.

PMID- 16281459
TI  - Sensitivity analysis of causal inference in a clinical trial subject to
      crossover.
AB  - In many clinical trials it is possible for some subjects to cross over between
      treatment arms. One can evaluate the effect of crossover by modeling it as a
      missing-data problem, where for subjects who cross over, one treats the
      unobserved value of the outcome in the original randomization arm as the missing
      data. The as-treated analysis is invalid if the crossover is nonignorable, in the
      sense that the crossovers represent a nonrandom sample of the randomized
      subjects. A recent area of general interest is the development of methods for
      measuring the sensitivity of inferences to nonignorability in the missing-data
      mechanism; one such approach is that of Troxel et al. In this paper we apply
      their method to the problem of measuring sensitivity to nonignorable crossover in
      randomized trials, extending it to the case where the crossover mechanism may
      differ between arms. Our method allows us to identify circumstances under which
      the as-treated analysis may be more or less sensitive to nonignorable crossover.
      We illustrate it with the example of a randomized clinical trial (RCT) in
      multiple sclerosis and a study of the effect of military service on income.

PMID- 16281460
TI  - Methodology of neuropsychological research in multicentre randomized clinical
      trials: a model derived from the International Subarachnoid Aneurysm Trial.
AB  - As advances in medicine and surgery lead to reductions in mortality rates for
      life-threatening conditions, it has become increasingly important to refine the
      methodology of auditing long-term morbidity. The inclusion of appropriate
      neuropsychological outcomes in a large multicentre randomized clinical trial
      poses considerable methodological and logistical difficulties. This paper
      presents a model developed to implement such a multicentre neuropsychological and
      quality of life audit for a subset of patients within the International
      Subarachnoid Aneurysm Trial (ISAT), the largest ever randomized trial in the
      treatment of subarachnoid haemorrhage. Based on our experience of collecting
      quality of life and neuropsychological outcomes from more than 550 patients, data
      are presented on the relative cost and efficacy of different organizational
      strategies, methods of canvassing patients and associated response rates. On the
      basis of this experience, we estimate a potential recruitment pool of 135 cases
      would be required to obtain some neuropsychological data on 100 cases. The design
      of any similar trial would therefore need to accommodate a loss to follow-up of
      approximately one third of the sample. In addition, our experience suggests that
      for a trial of this size and complexity, the deployment of centrally-based co
      ordinators travelling to satellite centres is more cost-effective than employing
      co-ordinators based at those centres. Extrapolations from the observations and
      calculations reported here can be employed as an evidence base to inform the
      design of neuropsychological outcome studies in large multicentre trials.

PMID- 16281461
TI  - Treatment effects monitoring committees and early stopping in large clinical
      trials.
AB  - BACKGROUND: Treatment effects monitoring is a process carried out over the course
      of a trial to determine whether it should continue unaltered. The purpose of
      monitoring is to protect persons enrolled from harm, caused either by exposure to
      an ineffective or harmful treatment or failure to provide a better treatment. The
      aim of this paper is to characterize treatment effects monitoring committees
      (TEMCs) as extant in published trials and to examine the effect of their presence
      on the premature stopping of a trial. METHODS: Trials published in 1990-1995 in
      the Annals of Internal Medicine, Archives of Internal Medicine, British Medical
      Journal, Journal of the American Medical Association, Lancet, New England Journal
      of Medicine or Controlled Clinical Trials were identified via MEDLINE (4279
      publications). Abstracts were screened to include only trials with parallel
      treatment designs and sample sizes of > or = 200, reducing the set to 661 papers.
      Those papers were then read, reducing the set to 562 after exclusion of papers
      not reporting trial results. The results that follow come from a review of these
      562 published papers and from the responses to two questionnaires. The first was
      mailed to the corresponding author, and the second to the chair of the monitoring
      body or other contact as provided by the author in response to the first
      questionnaire. RESULTS: Less than half (48%) of the 562 trials had TEMCs. Factors
      having a positive univariate relationship with the presence of a TEMC include
      National Institutes of Health (NIH) sponsorship, larger sample size,
      multicentered, longer data collection and follow-up, and mortality as an outcome.
      Most of the early stops occurred in trials with TEMCs (66 out of 78). The odds
      ratios for early stopping for trials with TEMCs versus those without TEMCs was
      4.4 (CI: 2.3-8.5). CONCLUSIONS: The evidence suggests that early stopping is
      associated with the presence of a TEMC, but a substantial number of trial reports
      do not mention the presence of a TEMC even when one was used to stop a trial
      early.

PMID- 16281462
TI  - Reported use of data monitoring committees in the main published reports of
      randomized controlled trials: a cross-sectional study.
AB  - BACKGROUND: We describe a review of published main reports of randomized
      controlled trials (RCTs), in order to measure the frequency of reported use of
      data monitoring committees (DMCs) and factors associated with reported DMC use.
      METHODS: Twenty-four higher impact general and specialist medical journals were
      handsearched for main reports of RCTs in order to provide a cross-sectional
      sample of trials published in the year 2000. Additionally, the same general
      medical journals were handsearched for 1990 to allow a comparison across time.
      RESULTS: Of 662 RCTs published in 2000, 120 (18%) explicitly reported using a
      DMC, while 107 (16%) reported planned interim analyses. Overall, about a quarter
      (24%) reported at least one of these. A higher proportion of trials reported
      using a DMC in 2000 than 1 990 (70/282, 25% versus 21/204, 10%) in the general
      medical journals. Logistic regression models suggested the more important
      variables associated with increased reported DMC use were: later year of
      publication, publication in general medical journal, survival-based endpoint,
      multicentre trial, increasing number of patients recruited, at least one arm
      involving a placebo, at least one arm involving a drug, factorial design and USA
      involvement in the trial. CONCLUSIONS: In 2000, about a quarter of main RCT
      reports mention use of a DMC. Actual use of DMCs is likely to be somewhat
      greater. Reporting use of a DMC was more likely for larger and longer trials
      among other factors. We believe the factors affecting reported use affect actual
      use. It is recommended that when a DMC oversees a trial, brief details should be
      explicitly included in the main trial paper. Standard nomenclature for DMCs is
      recommended.

PMID- 16281463
TI  - Systematic qualitative review of the literature on data monitoring committees for
      randomized controlled trials.
AB  - AIMS: To systematically review the published literature on data monitoring
      committees (DMCs) for randomized controlled trials (RCT) and summarize
      information and opinions on best practice. This was part of the DAMOCLES project.
      METHODS: A systematic and comprehensive search of five online bibliographic
      databases was performed, identifying 4007 potentially relevant articles. These
      were assessed in two stages by the authors. The 84 most relevant articles were
      agreed and were supplemented with extracts from 16 books: ultimately, 100 sources
      were reviewed. A series of 23 questions plus subquestions were developed to
      structure the data extraction and interpretation process. RESULTS: Much has been
      written about DMCs but by a rather small community of authors. The papers
      included some results of surveys, but were mainly opinion pieces based on the
      authors' beliefs, practices and experiences. There is a lack of empirical
      evidence for many aspects of DMCs. There was a great range of detail in the
      literature relating to the prespecified questions. It was generally agreed that
      interim monitoring of accumulating data was necessary in some form for most
      trials. Questions such as membership of the DMC featured widely in the literature
      with opinions and practice ranging from 3-20 members, of whom between none and
      all should be independent. There was a consensus that formal statistical methods
      should be used as tools to guide decision making rather than as hard rules.
      Conversely, topics such as the training and experience required for DMC
      membership were discussed in very few papers. CONCLUSIONS: There is a consensus
      in the published literature in a number of areas, although there are many
      different models for structure and functions of a DMC. While uncertainty remains
      about some issues, it is strongly recommended that an explicit set of guidelines
      (Charter) is prepared for each DMC prior to the start of the trial specifying
      clearly how it will operate.

PMID- 16281464
TI  - Lessons for cluster randomized trials in the twenty-first century: a systematic
      review of trials in primary care.
AB  - BACKGROUND: Evidence suggests that cluster randomized trials are often poorly
      designed and analysed. There is little recent research on the methodologic
      quality of cluster randomized trials and none focuses on primary health care
      where these trials are increasingly common. METHODS: We conducted a systematic
      review of recent cluster randomized trials in primary health care, searching the
      Cochrane Controlled Trials Register. We also searched for unpublished trials in
      conference proceedings, and the UK National Research Register. We assess
      methodologic quality using a checklist, articulate problems facing investigators
      conducting these trials, and examine the extent to which carrying out a cluster
      randomized trial (as opposed to an individually randomized trial) in primary care
      may reduce power. RESULTS: We found 367 trial reports. Many trials were reported
      more than once. We characterize 152 independent cluster randomized trials in
      primary health care published between 1997 and 2000, and briefly describe 47
      trials unpublished at December 2000. The quality of design and analysis was
      variable. Of published trials reporting sample size calculations 20% accounted
      for clustering in these calculations, 59% of published trials accounted for
      clustering in analyses. Unpublished trials were more recent and of higher
      quality. Reporting quality was better in journals reporting more cluster
      randomized trials. Many trial investigators reported problems with adherence to
      protocol, recruitment and type of intervention. CONCLUSIONS: Methodologic quality
      of cluster randomized trials in primary health care is variable and reporting
      needs improvement. The use of cluster randomization should be indicated in the
      title or abstract so these kinds of trials are easier to identify. Communicating
      appropriate methodology to health care researchers continues to be a challenge.
      Cluster randomized trials should always be piloted and information from pilots
      and unsuccessful trials shared more widely.

PMID- 16281465
TI  - The Complications of Age-Related Macular Degeneration Prevention Trial (CAPT):
      rationale, design and methodology.
AB  - BACKGROUND: The Complications of Age-Related Macular Degeneration Prevention
      Trial (CAPT) is a randomized clinical trial to evaluate whether prophylactic
      laser treatment to the retina can prevent the complications of the advanced stage
      of Age-Related Macular Degeneration (AMD), the leading cause of irreversible
      blindness. METHODS: CAPT is conducted in 23 clinical centers and in three central
      resource centers. The primary outcome measure is change in visual acuity;
      secondary outcomes include the incidence of complications of AMD, changes in
      other measures of visual functioning and vision-related quality of life. In
      total, 1052 patients with two high-risk eyes were enrolled. One eye was
      randomized to receive laser treatment and the other eye to observation. All
      patients were treated immediately after randomization and again at 12 months,
      dependent on clinical status. All patients are followed via study visits and
      telephone calls for a minimum of five years. Study visit procedures include
      established tests of visual function conducted by examiners masked to the
      treatment assignment of each eye, a biomicroscopic examination by
      CAPTophthalmologists, and photographs of each eye taken according to protocol and
      assessed by masked graders in a centralized Photograph Reading Center. RESULTS:
      This paper describes the CAPT study, including study rationale, operational
      structure, and measures implemented to ensure standardization of assessments,
      adherence to protocol, quality assurance, and maintaining follow-up. Several
      features related to study design and procedures that are specific to CAPT are
      highlighted, including clinic selection and judgements regarding patient
      eligibility. CONCLUSIONS: An intervention that can reduce the risk of advanced
      AMD by 30% in the eyes of people with two high-risk eyes may halve the rate of
      bilateral blindness from AMD. It would also yield substantial savings in
      expenditures devoted to treating advanced AMD and the disability it causes, and
      enhance the quality of life for people at risk.

PMID- 16281466
TI  - Using clinical trials as a condition of coverage: lessons from the National
      Emphysema Treatment Trial.
AB  - In making evidence-based coverage decisions, The Centers for Medicare & Medicaid
      Services (CMS) often must balance the need for rigorous evaluation of medical
      technologies with the public's demand for rapid access to new services. During
      the mid-1990s, this dilemma was apparent with regard to a promising, yet
      unproven, new procedure for emphysema patients known as lung volume reduction
      surgery (LVRS). In a unique decision, CMS provided coverage for LVRS only under
      the protocol of the National Emphysema Treatment Trial (NETT), which it
      cosponsored with the National Heart, Lung, and Blood Institute. The CMS has
      recently revised its coverage policy for LVRS based on the results of the NETT.
      This paper provides a history and rationale for CMS's approach to paying for
      LVRS. It also discusses lessons learned from the NETT experience and potential
      implications for future collaborations between health plans and the clinical
      research enterprise that would provide better information for coverage treatment
      decisions.

PMID- 16281467
TI  - The Salk Polio Vaccine Trial of 1954: risks, randomization and public involvement
      in research.
AB  - The year 2004 marks the fiftieth anniversary of the celebrated 1954 Salk Polio
      Vaccine Trial. This enormous clinical trial, involving 1.8 million children, was
      carried out with the co-operation and assistance of hundreds of thousands of lay
      volunteers, along with medical professionals and local health departments
      throughout the USA. While the trial was an impressive public health achievement,
      firmly establishing the efficacy of the killed virus vaccine and paving the way
      for eradication of the disease, it was not without controversy. This article
      recounts the story of this important early clinical trial and how the social and
      political conditions at the time affected its planning and execution.

PMID- 16281468
TI  - A conversation with Paul Meier. Interview by Harry M Marks.

PMID- 16281469
TI  - [Guide for peer reviewers of scientific article].
AB  - Despite its shortcomings, peer review is still the best tool of scientific
      publishing. It brings benefits not only to the journal and its authors, but to
      the peer reviewers: they are privileged to have an insight into the latest
      research and still unpublished results in their scientific field. Reviewers also
      build up their ability to critically assess scientific papers, which may be
      useful in their own professional work and development. We wrote these brief
      guidelines to help Croatian-speaking physicians to satisfactorily respond in case
      they receive a scientific journal editor's request for a manuscript review. The
      guidelines were created primarily for new reviewers, but they may be useful as a
      refresher text for experienced reviewers.

PMID- 16281470
TI  - [Advanced myocardial ischemia in patients with diabetes mellitus--early results
      of surgical treatment].
AB  - In this restrospetive study, data on 272 coronary artery disease patients with
      concomitant diabetes mellitus treated between 12/1997 and 12/2002 were analyzed.
      Eighty patients inderwent complete arterial revascularization (DM-ART), whereas
      192 patients underwent coronary revascularization using arterial-venous grafts
      (DN-NEART). The following preoperative data and risk factors were analyzed:
      arterial hypertension, hyperlipoproteinemia, number of vessels involved, left
      coronary artery stenosis, unstable angina, previous myocardial infarction (MI),
      previous cardiac surgery, EuroScore. During a 30-day postoperative period, the
      following complications were analyzed: bleeding, perioperative MI, wound
      infection, sternal dehiscence, neurologic dysfunction, mortality. DM-ART patients
      had a higher rate of hyperlipoproteinemia (p=0.004). Difference was only found
      for the occurrence of perioperative MI in DM-NEART group (p<0.001). Total
      arterial revascularization without cardiopulmonary bypass is a reliable and safe
      choice in patients with concomitant diabetes mellitus irrespective of its type.
      Definitive conclusions can only be made after five- or ten-year evaluation of
      postoperative mirbidity and mortality.

PMID- 16281471
TI  - [The impact of glucose absorbed from dialysis solution on body weight gain in
      peritoneal dialysis treated patients].
AB  - A proportion of peritoneal dialysis (PD) patients experience substantial body
      weight (BW) gain with time. It is caused by fat tissue accumulation or fluid
      retention. It is believed that fat tissue accumulates due to caloric contribution
      of glucose absorbed from dialysis solution or to the mitochondrial fat regulatory
      uncoupling protein (UCP) gene polymorphism. This study examined BW fluctuations
      in 40 patients (24 females, 16 males), treated by PD at least 36 months (initial
      mean age 54.50+/-9.00 years, mean BW 68.00+/-8.50 kg and mean height 164.00+/
      8.50 cm), relation of the BW fluctuation and caloric contribution of glucose
      absorbed from dialysis solution and characteristics of the patients with BW gain.
      Initial BW increased after 6, 12, 24 and 36 months by 5.90+/-3.50 kg, 7.90+/-4.90
      kg, 9.50+/-5.00 and 11.00+/-5.00 kg, or for 8.68, 11.62, 13.97 and 16.18% of the
      initial value, respectively. After the first 6 and 12 months 38 patients gained
      weight, 39 after 24 and all 40 patients after 36 months. There was not
      significant correlation between BW gain and caloric contribution of glucose
      absorbed from dialysis solution. Female patients had initially lower BW, but for
      the first 12 months period significantly increased BW more than males, and not
      for the other observed periods. High transporters (patients with higher
      transport, higher transmission of glucose from peritoneal solution into the
      blood, and urea and creatinine in the opposite direction, with rapid decrement of
      osmolality gradient between dialysate and blood that is necessary for excessive
      fluid elimination), had lower initial BW and, although without statistical
      significance, only within the first period increased BW more than low
      transporters. In conclusion, with time BW gain was found in all the PD dialysis
      patients, it was not related to caloric contribution of glucose absorbed from
      dialysis solution, and women and high transporters increased BW weight more than
      men and low transporters in the first year of treatment. The BW gain is at least
      in part caused by fluid retention.

PMID- 16281472
TI  - [Optic nerve injury from the medical expertise point of view].
AB  - The optic nerve can be injured directly or indirectly. Direct injury occurs in
      association with orbital or craniocerebral injury with interruption of anatomical
      and functional optic nerve integrity. Indirect injuries occur when the force of
      impact is transmitted to the optic nerve. In the indirect injury group the mostly
      false diagnosed is traumatic opticoneuropathy especially after whiplash injury.
      According to Quebec classification, after whiplash injury Ist to IIIrd degree,
      ophthalmologic examination or visual field testing is not necessary, because
      there is no possibility of optic nerve injury. The first signs of injured optic
      nerve are the loss of maximal visual acuity and the presence of pupillary defect.
      High doses of glucocorticoids or surgical decompression can be applied in the
      treatment of traumatic opticoneuropathy.

PMID- 16281473
TI  - [Ocular manifestations in patients with human immunodeficiency virus infection
      before and after the introduction of highly active antiretroviral therapy].
AB  - The aim of this study was to determine and compare the incidence of various
      ophthalmlogic changes before anfd after the initiation of highly active
      antiretroviral therapy (HAART) in HIV-infected patients treated at the University
      Hospital for Infectious Diseases "Dr. Fran Mihaljevic" in Zagreb. This
      retrospective longitudinal analysis included all adult patients with confirmed
      HIV-1 infection divided into two groups: period before HAART (1995-1997) and
      period after HAART (1998-2000). Only those patients who underwent at least two
      ophthalmologic examinations in any of the two or in both periods were considered
      eligible. In total, 85 patients were enrolled in the study, 50 during the 1995
      1997 period and 47 in the period 1998-2000 (12 patients were monitored in both
      periods). The mortality rate was significantly lower in patients treated during
      the HAART era, with an average decrease in mortality rates of 59.3%. During the
      period of ophthalmologic monitoing from 1995 to 1997, only 9 (18%) patients
      received HAART, and 33 (70.2%) in the period 1998-2000. In total, 208 ophthalmic
      abnormalities were recorded, 132 (63.5%) in the first and 76 (36.5%) in the
      second period. Vascular changes were most frequently diagnosed (113/208 or 54.3%
      cases) of which cotton-wool exudates in 55 and microaneurysms in 54 cases.
      Cytomegalovirus (CMV) retinitis was most commonly diagnosed among infectious
      ocular complications (altogether 39 episodes). Changes in the anterior segment
      were observed in only 11/208 (5.3%) cases, while neuro-ophthalmic manifestations
      were sees in 39/208 patients (18.7%). The incidence of CMV-retinitis episodes in
      the first monitored period was 57.2 (95% CI, 38.5-86.6) per 100 years of follow
      up and in the HAART era 7.6 (95% CI, 1.6-22.4; p<0.0001) per 100 years of follow
      up. The visual acuity in patients from the HAART era was significantly more
      frequently preserved than in patients from the pre HAART era on follow-up
      examinations (p<0.001). Our study showed that the incidence of CMV-retinitis
      declined significantly in the period 1998-2000, while the decrease in the
      incidence rates of other ocular manifestations was less profound. In contrast to
      the pre HAART era, there was no worsening of visual acuity in the HAART era.

PMID- 16281474
TI  - [Hemorrhoids--diagnosis and treatment options].
AB  - Hemorrhoids are a common condition in adult population with prevalence of about
      4%. Only a third of patients with symptomatic hemorrhoids seek medical help. The
      annual rate of office visits for hemorrhoids is 12 for every 1000 patients in the
      United States. Hemorrhoids consist of connective tissue cushions surrounding
      direct arteriovenous communication. They can cause bleeding, pain and itching but
      other anorectal diseases should be ruled out. Current guidelines recommend a
      minimum of anoscopy and flexible sigmoidoscopy for bright-red rectal bleeding.
      Care depends on the extent of hemorroids. First-degree hemorrhoids can be managed
      with medical treatment. Surgery is reserved for patients with third and fourth
      degree hemorrhoids and failure of nonoperative treatment. A new method of the
      stapled hemorrhoidectomy has been introduced which significantly reduces
      postoperative pain, hospital stay and use of analgesics with results that are
      equal to excisional hemorrhoidectomy.

PMID- 16281475
TI  - [The importance of the team work in diagnosis of pituitary adenomas: the five
      tier World Health Organization classification].
AB  - In the last ten years great changes occurred concerning the basic knowledge on
      pituitary adenomas. Many different classifications of pituitary adenomas were
      proposed. In 2000 World Health Organization accepted the five-tier classification
      of pituitary adenomas proposed by Kovacs and Horvath. It is based on clinical and
      biochemical results, neuroradiological imaging, operative findings,
      pathohistological examination, immunocytochemistry and electron microscopy
      studies on more than 10 000 surgically treated pituitary adenomas. Its importance
      is that it supplies the endocrinologist, neurosurgeon and oncologist with
      valuable information concerning the biological behavior, growth potential,
      treatment response and prognosis of pituitary adenomas. Due to the financial
      restraints, lack of facilities and unavailability of well trained personnel this
      five-tier classification cannot be fully implemented at our institution.
      Nonetheless, a perfectly useful diagnosis may be made in instances of limited
      sources. Clinical, biochemical, neuroradiological and intraoperative data coupled
      with basic histology are fundamental. Together with the novel biological
      techniques that provide the data on tumor's growth rate, aggressiveness and
      invasiveness, they ar necessary in establishing the correct diagnosis which will
      direct patient's future treatment. We strongly advocate in favor of this five
      tier classification of pituitary neoplasms and hope it will reach the full
      implementation.

PMID- 16281476
TI  - [Biochemical markers of bone turnover--clinical application and limitations].
AB  - Biochemical markers of bone turnover detect activity of bone cells, namely
      osteoblasts and osteoclasts. Osteoclasts resorb bone, and fragments of collagen
      type I (telopeptides, pyridinolines) are released into extracellular fluid and
      subsequently transported in blood and urine. Osteoblasts synthesise bone matrix
      proteins, among which are some of clinical significance: collagen type I
      propeptide, osteocalcin and bone alkaline phosphatase. Considerable scientific
      evidence has demonstrated that biochemical markers of bone turnover enable
      insight into dynamics of bone turnover, growth and repair. The most comprehensive
      data are available for the monitoring of osteoporosis treatment effects, for
      which use clinical guidelines have been defined. Measurement of biochemical
      markers of bone turnover in other metabolic bone disorders and malignant diseases
      with skeletal involvement is important in diagnostic assessment and therapy
      monitoring. Interpretation of results should take into consideration biological
      variations of these analytes.

PMID- 16281477
TI  - [Role of physicians in violence against women in family].
AB  - Health protection of every individual is the main goal of health activity and
      because of that violence against women in family is important everyday health
      issue in Croatia. The principles of medical science and the principles of
      professional ethics oblige us to search the real causes of illness, even if
      causes are not of biological basis. Physicians and the rest of health workers
      have duty to have knowledge about signs of violence on women, denounce to
      competent authorities every case of violence against women in family and give
      adequate medical treatment and healing. In this review article were used medical,
      judicial, victimological and sociological literature, because only through co
      ordinated and responsible co-operation with social service, administration of
      justice, police, non-government associations and the rest of professionals
      involved in victim protection, we can help women to live in healthier family
      union.

PMID- 16281478
TI  - [Croatian Medical Association, Andrija Stampar and public health politics in the
      Kingdom of Serbs, Croats and Slovenians (Kingdom of Yugoslavia)].
AB  - The research on work of doctor Andrija Stampar (1888-1958) as the head of the
      Hygienic division of The Ministry of Public Health of the Kingdom of Serbs,
      Croats and Slovenians from 1919 till 1929-1931 is presented, as well as the
      influence of the Health Section of the League of Nations and Rockefeller
      Foundation. Special attention is also given to the resistance of practicing
      physicians around the Croatian Medical Association in Zagreb to Stampar's project
      of socialization of medicine. In addition, I will elaborate on the changing of
      the official public health politics after Stampar's dismissal from the Ministry
      in 1931, as well as the new changes connected with the founding of politically
      more independent province - Banovina Hrvatska in 1939. The article is mostly
      based on unpublished archival sources about the life and work of A. Stampar, as
      well as the documentation of Rockefeller Foundation.

PMID- 16281479
TI  - [Is erythropoietin just a promoter of erythropoiesis?].

PMID- 16281480
TI  - [Treatment of ischemic heart disease: old traditions and new trends].

PMID- 16281481
TI  - [Variants of heart remodeling in essential hypertension: prevalence and
      determinants].
AB  - AIM: To study myocardial remodeling (MR) in hypertensive patients with normal and
      excessive body mass, to analyse MR features depending on clinical and hemodynamic
      parameters. MATERIAL AND METHODS: Structural-functional conditions of the
      myocardium were studied with echocardiography, and determination of left
      ventricular remodeling (LVR) type was made in 734 untreated hypertensive patients
      aged 19-76 years. RESULTS: Patients with essential hypertension (EH) stage I had
      mostly excentric left ventricular hypertrophy (LVH). The number of patients with
      concentric LVH increases with age, disease severity. This type of LVH occurs more
      frequently in males than in females. In females, LVH severity depends, primarily,
      on the degree of obesity. If EH combines with obesity, structural alterations of
      the myocardium are more prominent than in isolated pathology. In android obesity,
      LVH is more frequent. CONCLUSION: In EH, structural alterations of the heart and
      a LVR variant are determined, besides arterial pressure, by such factors as age
      and gender, duration of EH, obesity, its degree and kind.

PMID- 16281482
TI  - [I/D-polymorphism of ACE gene, morphofunctional heart condition and blood
      pressure 24-h profile in young men with arterial hypertension].
AB  - AIM: To study the effects of ACE gene polymorphism on morphofunctional condition
      of the heart and 24-h blood pressure profile (BPP) in young men with
      hypertension. MATERIAL AND METHODS: A total of 174 young and middle-aged
      hypertensive men (mean age 32 +/- 4.6 years and 48 +/- 3.1 years, respectively)
      were examined (echocardiography, 24-h BP monitoring, tests for I/D-polymorphism
      of ACE gene). RESULTS: Genotype ID appeared most prevalent both in the young and
      middle-aged examinees (56 and 49%, respectively). Interventricular septal
      thickness and left ventricular myocardial mass were the largest in young
      hypertensive patients carrying genotype DD. Mean 24-h and nocturnal diastolic BP
      was significantly higher in young hypertensive patients with genotype II vs
      middle-aged patients with the same genotype. Carriers of genotype II had maximal
      variability of systolic and pulse blood pressure. CONCLUSION: Genotype DD
      appeared most unfavourable in relation to left ventricular myocardial
      hypertrophy. Its carriers had the thickest right ventricular myocardium, the
      largest mass of the left ventricle. Homozygotes by allele-I had most pronounced
      changes in a 24-h BP profile.

PMID- 16281483
TI  - [Intrarenal hemodynamics and blood pressure in hypertensive patients with renal
      artery anomalies].
AB  - AIM: To determine characteristics of a clinical course, 24-h profile of arterial
      pressure (AP), of renal hemodynamics, involvement of target organs in patients
      with arterial hypertension (AH) of the third degree and anomalies of renal
      arteries. MATERIAL AND METHODS: 24-h monitoring of AP, echocardiography,
      measurement of microalbuminuria, renal hemodynamic were made in 15 patients (9
      female, 6 male) having resistant AH of the third degree and different anomalies
      of renal arteries (mean age 45.3 +/- 1.9 years). The control group consisted of
      patients with essential AH stage III (mean age 45.3 +/- 1.8 years). The groups
      were comparable by sex, age, duration of AH. RESULTS: The patients of the study
      group had a significantly lower pulsatility index in the renal artery and
      interlobular level and resistance index at the segmental and interlobular level
      of the RA on the side of the anomaly. There was a significantly higher minimal
      diastolic blood flow velocity in the segmental level of RA on the side of the
      anomaly. Renal scintigraphy revealed a decreased index of radiopharmaceutical
      accumulation. A positive correlation was found between the pulsatility index,
      resistance at a segment RA level and variability, an increase of morning
      diastolic blood pressure. The groups had significant differences neither by 24-h
      AP indices nor by severity of target organ lesion. CONCLUSION: Patients with RA
      anomalies have specific renal hemodynamics determining renal hypoperfusion on the
      side of the anomaly which may be involved in development of resistance to
      hypotensive therapy.

PMID- 16281484
TI  - [Immunological mechanisms in pathogenesis of coronary atherosclerosis].
AB  - AIM: To evaluate functional parameters of immune system in patients with
      different variants of ischemic heart disease (IHD): stable angina pectoris and
      myocardial infarction; the role of immunological disorders in pathogenesis of
      IHD. MATERIAL AND METHODS: Immunological investigation of 136 IHD patients (102
      with stable angina and 34 with myocardial infarction) included the study of the
      phenotype of lymphocytes: CD3, CD4, CD8, CD16, CD19, CD11/18, CD25, CD95 and HLA
      DR. Measurements were made of serum concentrations of IL-1beta, IL-2, IL-6, IL-8,
      TNF-alpha, rIL-2 and expression of mRNA IL-1beta, IL-2, IL-6, TGFb1 in vascular
      wall of patients with coronary atherosclerosis (angina pectoris, myocardial
      infarction). RESULTS: One of the basic mechanisms taking part in development of
      atherosclerosis is immune-mediated inflammation of the vascular wall.
      Inflammatory cytokines have a significant role in this process. The serum levels
      of IL-1beta, IL-2, IL-6, IL-8, TNF-alpha in patients with coronary
      atherosclerosis were found to be significantly higher than in healthy controls.
      The study of IL-1beta, IL-2, IL-6, TGFb1 in tissue revealed that radial artery
      wall contains mRNA of the cytokines. The main cytokine of the aorta appeared to
      be IL-2, and the main peripheral artery cytokines were IL-1beta, IL-6.
      CONCLUSION: Increased serum concentrations of IL-1beta, IL-2, IL-8 in patients
      with coronary atherosclerosis reflect immune-inflammatory nature of the disease.
      Detection of dissimilar cytokines in tissue sampling reflects not only different
      degree of vascular involvement in the process but also phase evolution of the
      disease. Coronary atherosclerosis may result in adaptive immune response.

PMID- 16281485
TI  - [Serum levels of sexual hormones in young and middle-age healthy subjects with
      risk factors of coronary heart disease and patients with coronary heart disease].
AB  - AIM: To study sexual hormones levels in risk of beginning and development of
      coronary heart disease (CHD) in young and middle-aged (up to 50 years) men and
      women. MATERIAL AND METHODS: Sexual hormones were studied in 105 patients (53
      males and 52 females) aged 25-50 years. Of them, 88 suffered from IHD and 17 had
      CHD risk factors. Twenty healthy controls were matched by age and gender. LH,
      FSH, estradiol, testosteron were measured in blood serum by enzyme immunoassay
      (Elecsys kit, Beringer Mannheim). RESULTS: Young and middle-aged (under 50 years
      of age) males and females with IHD or its risk factors have changed levels of
      sexual hormones. CONCLUSION: In IHD male hormones levels increase in women but
      decrease in men while female hormones increase in men and decrease in women.

PMID- 16281486
TI  - [Five-year trends in main risk factors of coronary heart disease among open
      population of Tyumen].
AB  - AIM: To study five-year trends in main risk factors of coronary heart disease
      (CHD) among 35-54-year-old population of Tyumen. MATERIAL AND METHODS: Five-year
      monitoring of 1597 males and females aged 35-54 years was performed as two
      cardiological screening trials. The risk factors were assessed both by standard
      and extended WHO criteria. RESULTS: Risk factors studied had the following
      prevalence trends: a rise in the rate of obesity (7.2-14.5%),
      hypercholesterolemia by standard criteria (14.4-27.8%) and hypertriglyceridemia
      (5.8-16.7%) among men aged 35-44 years; a rise of the rate of isolated systolic
      arterial hypertension by extended criteria (3.5-8.8%), smoking (10.6-19.2%), hypo
      alphacholesterolemia (3.9-11.6%) among women aged 35-44 years; a rise in the rate
      of isolated systolic arterial hypertension (3.9-14.7%), a decrease of diastolic
      arterial hypertension rate by extended criteria (49.0-31.3%) among women aged 45
      54 years. Five-year monitoring revealed that among 45-54-year-old men the number
      of those who smoke irregularly significantly increased (7.3-21.5%), while the
      number of non-smokers fell (44.3-21.5%). CONCLUSION: Tyumen population is
      characterized by a high prevalence of the risk factors with a negative 5-year
      trend. The results of the screenings give grounds for conduction of a large-scale
      prophylactic program in an open Tyumen population with a focus on priorities of
      prophylactic interventions.

PMID- 16281487
TI  - [Apolipoprotein B100 as a risk factor of acute coronary syndrome and this risk
      factor effect on arterial hypertension in patients with ischemic heart disease].
AB  - AIM: To clarify correlations between an elevated concentration of apolipoprotein
      B100 (apoB) in blood plasma and risk of acute coronary syndrome (ACS); to study
      apoB level in hypertensive patients and its correlation with ischemic heart
      disease (IHD) risk in these patients. MATERIAL AND METHODS: Lipid serum spectrum
      (cholesterol, triglycerides (TG), lipoprotein a (Lpa) and apoB was studied in 456
      patients with ACS by NYHA criteria, 119 patients with chronic IHD and 86 patients
      free of cardiovascular diseases (controls). All 575 patients with IHD were
      divided into those with and without hypertension (426 and 149 patients,
      respectively). RESULTS: Lpa was significantly higher in patients with ACS; apoB
      was higher in ACS and chronic IHD patients. ApoB was higher in IHD normotensive
      patients than in controls and higher in IHD hypertensive patients than in IHD
      normotensive patients and in the control group. Lpa in IHD hypertensive patients
      was significantly higher (p < 0.045) than in the controls as well as TG (p <
      0.05). By the other parameters the groups did not differ. CONCLUSION: The blood
      plasma level of apoB higher than 130 mg/dl is an independent and significant risk
      factor of ACS in IHD patients especially at the age under 60. The level of apoB
      over 115 mg/dl is a significant risk factor of IHD. The significance of this
      lipid factor rises in concomitant hypertension.

PMID- 16281488
TI  - [Disturbance of endothelium-dependent vasodilation and morphological changes of
      the radial artery in patients with coronary heart disease].
AB  - AIM: To elucidate whether endothelium-dependent vasodilation (EDVD) is a method
      of early diagnosis of endothelial dysfunction or is a sign of established
      morphological changes in the vascular wall. MATERIAL AND METHODS:
      Endothelialfunction was studied in 44 males with essential hypertension (EH)
      (mean age 46.9 +/- 0.9 years), in 52 patients with coronary heart disease (CHD)
      (mean age 50.0 +/- 0.9 years) after mammary-coronary and aortocoronary bypass
      operation with use of radial artery (RA), and in 28 healthy males (mean age 44.2
      +/- 1.2 years). Intraoperative RA biopsy results for patients with ischemic heart
      disease after coronary artery bypass grafting with RA as an arterial graft were
      analysed. RESULTS: Patients with CHD showed thicker complex intima-media (TIM) of
      the common carotid arteries compared to control and hypertensive patients free of
      CHD clinical symptoms. This is associated with lowering of EDVD in RA and,
      therefore, suggests systemic occurrence of endothelial dysfunction. The
      histological study of RA has found hyperplasia of the internal vascular intima of
      1.1 +/- 0.2 degree in 97% of CHD patients. Combination of CHD with hypertension
      showed thicker intima, higher index of intima thickness and RA narrowing
      percentage vs such parameters in CHD free of hypertension. CONCLUSION: Impaired
      EDVD in the test with reactive hyperemia is due to morphological changes in the
      radial artery, its intima. The degree of changes in endothelial vascular
      reactions in RA is closely related to severity of systemic atherosclerosis. In
      CHD, RA has a marked intimal hyperplasia which leads to vasospasticity and may
      result in development of stenosis in its use as a graft for myocardial
      revascularization. One of the basic factors influencing the degree of intimal
      hyperplasia of the radial artery is severity of arterial hypertension.

PMID- 16281489
TI  - [Multidirectional effects of exercise of various type and intensity on lipid
      transport system of blood in healthy subjects and patients with coronary heart
      disease].
AB  - AIM: To evaluate effects of dynamic exercise (DE) and static leg exercise (SE)
      varying by intensity on blood serum spectrum of lipoproteins and apolipoproteins
      in healthy persons and patients with coronary heart disease (CHD). MATERIAL AND
      METHODS: Healthy 12 men and 12 CHD patients of functional class I performed
      bicycle DE of maximal (for age) intensity (100%), submaximal (80, 70 and 60%), SE
      of maximal and submaximal intensity. Blood samples were taken before the
      exercise, after it and 3 hours after the exercise. RESULTS: DE of high intensity
      (80% and higher) and SE of maximal and moderate intensity (100 and 60%,
      respectively) produced atherogenic changes in the blood of both healthy subjects
      and CHD patients: a rise in total cholesterol, LDLP cholesterol, triglycerides,
      apolipoprotein (apo) B and apo B/ apo AI. Moderate (60%) DE gave rise to
      antiatherogenic changes in the blood: a fall in lipoproteins containing apoB and
      a rise in concentration of apo AI both in healthy and CHD subjects. CONCLUSION:
      To prevent atherosclerosis by correction of atherogenic lipid disorders, CHD
      patients and healthy persons should do DE of moderate intensity in addition to
      other prophylactic measures.

PMID- 16281490
TI  - [Two-year results after implantation of a metallic stent EPHESOS in patients with
      coronary heart disease].
AB  - AIM: To evaluate two-year results of using a metallic stent EPHESOS in patients
      with native atherosclerotic lesion of coronary arteries (without prior
      interventions). MATERIAL AND METHODS: The stent was implanted to 731 patients.
      53% had manifestations of unstable angina. 42% of the lesions were complicated.
      The length of the stenosis was 15.5 +/- 6.8 mm, 44% stenoses were long. RESULTS:
      The success of stenting was 99.6%. Cases of acute and subacute thrombosis were
      absent. Non-Q wave myocardial infarction in primary hospitalization developed in
      4 patients. For 6 months, cardiovascular complications (death, angina,
      restenosis, repeated revascularization) occurred in 21%. Angiographic control
      follow-up of 6 months maximum covered 329 (45%) patients. Hemodynamically
      significant restenosis was detected in 18% patients. Cardiovascular complications
      for 24 months occurred in 39%. CONCLUSION: The EPHESOS stent has demonstrated a
      stable long-term effect on prevention of thrombosis and restenosis in the
      majority of patients with a relatively high risk of intervention.

PMID- 16281491
TI  - [Effects of aggressive therapy with simvastatin in patients with acute coronary
      syndrome and initially normal level of LDLP cholesterol on cardiovascular
      outcomes (LAOKOON). Pilot randomized trial].
AB  - AIM: To examine anti-inflammatory effect of statins on outcomes of acute coronary
      syndrome (ACS). MATERIAL AND METHODS: The trial included 211 ACS patients without
      ST elevation at ECG. The patients were followed up for 180 days. The anti
      inflammatory action was studied for 30 days. The patients were divided into two
      groups by the treatment: simvastatin 10 mg + aspirin 325 mg (104 patients, group
      1) and simvastatin 40 mg + aspirin 325 mg (107 patients, group 2) for 30 days.
      RESULTS: Simvastatin in maximal dose lowed LDLP cholesterol from 101 +/- 9.8 to
      72 +/- 3.3 mg/dl, in a minimal dose--from 104 +/- 11.3 to 81 +/- 2.1 mg/dl (p <
      0.05). Only maximal dose simvastatin produced a significant reduction of C
      reactive protein (CRP) to the disease day 14. The integral index including all
      cases of cardiovascular death +acute myocardial infarction+progressive
      angina+rehospitalization was 70 scores for group 1 and 137 for group 2 (p =
      0.047). CONCLUSION: Use of simvastatin in ACS patients, initially normal level of
      LDLP cholesterol and elevated level of CRP produced a dose-dependent effect,
      alleviated inflammation and improved the disease course.

PMID- 16281492
TI  - [An 8-year study of depression effects on myocardial infarction risk in a
      population of 25-64 year old men].
AB  - AIM: To study depression effects on the risk of myocardial infarction (MI) for 8
      years in men aged 25-64 years. MATERIAL AND METHODS: A random representative
      sample of men (n = 657) at the age between 25 and 64 living in Novosibirsk were
      screened in 1994 in the scope of WHO program "MONICA-psychosocial". The response
      was 82.1%. WHO "Register of Acute Myocardial Infarction" detected 58 cases of MI
      in the control period 1994-2002. Statistics were obtained with the program set
      SPSS-10. Cox regression model was used for estimation of a relative MI risk
      (RMIR). RESULTS: RMIR in 25-64-year-old men for 8 years was 2-fold higher in men
      with depression than without it, in the age group of 55-64-old men--5-fold.
      Depression was in 65.8% MI patients. The highest RMIR was in men with depression
      engaged in hard labour, retired, poorly educated, divorced, widowed. CONCLUSION:
      Risk of MI in men is related to depression due to social and economic status.

PMID- 16281493
TI  - [Catalytic autoantibodies in autoimmune myocarditis: clinical and pathogenetic
      implications].
AB  - AIM: To evaluate pathogenetic and clinical significance of autoantibodies (AAB)
      with catalytic activity in the serum of patients with autoimmune myocarditis
      (AM). MATERIAL AND METHODS: The study was made on the sera from 99 patients with
      AM of different course: malignant, benign, myocardiosclerosis (MCS). In addition
      to standard immunological parameters, the study was made of serum levels of
      anticardiomyosine-antiCM (protabzymes) and anti-DNA (DNA-abzymes) of AAB. After
      obtaining anti-CM and anti-DNA IgG-AT, we determined non-specific and specific
      proteolytic activity of anti-CM. RESULTS: Maximal specific activity of
      protabzymes was seen in 73% patients with malignant AM, it correlated with blood
      levels of anti-CM AAB, DNA-abzymes activity was very high in 45% patients. In MCS
      proteolytic activity of autoAT was absent in 61% patients. In benign AM
      occurrence of protabzymes was confirmed in 35% cases. Elevated DNA-hydrolyzing
      activity of DNA-abzymes occurred in 13% cases. The activity had no significant
      correlation with serum titers of AB. In MCS proteolytic activity of AAB was
      absent in 61% cases, but high activity of anti-CM AAB was in 28%. The activity of
      DNA-abzymes in 44% ranged considerably which, in seropositive cases, detected
      significant correlation with serum titers of DNA-binding autoAT. CONCLUSION:
      Evaluation of catalytic activity of AAB may be considered as a criterial test
      assessing the stage, clinical variants and severity of AM. It also permits
      formulation of the disease prognosis and its possible outcomes.

PMID- 16281494
TI  - [The role of plasmatic erythrocytic membrane in formation of hypoxia in patients
      with chronic cardiac failure].
AB  - AIM: To study oxygen supply to erythrocytes in patients with chronic cardiac
      failure as a factor provoking hypoxia. MATERIAL AND METHODS: The trial enrolled
      12 men with chronic cardiac failure (CCF) of functional NYHA class II aged 37 to
      74 years (group A). Group B--healthy donors (n = 10) aged 20-40 years.
      Conformation changes of hemoporphirine were detected with degradation
      spectroscopy, viscosity of plasmatic membrane--with resonance spectroscopy.
      Degradation spectroscopy estimated content of Hb-ligant complexes as 0.34 +/-
      0.013; complexes I Hb-NO 0.73 +/- 0.11, complexes II Hb-NO 0.28 +/- 0.08 (group
      A). RESULTS: Electronic-paramagnetic spectroscopy has estimated: S--0.716 +/-
      0.005 (group A), 0.667 +/- 0.011 (group B). In group B- 0.5 +/- 0.08; 0.41 +/-
      0.22; 0.55 +/- 0.12, respectively. CONCLUSION: Patients with CHF have high
      microviscosity of plasmatic erythrocytic membrane near location of polar lipid
      groups; subnormal content of oxyhemoglobin and elevation of the number of
      complexes of nitric hemoglobin-oxide; altered binding of nitric oxide with
      hemoglobin.

PMID- 16281495
TI  - [Low ability of blood lymphocytes to produce interferon-gamma in patients with
      idiopathic prolapse of mitral valve].
AB  - AIM: To examine lymphocyte ability to synthetize interferon-gamma in patients
      with mitral prolapse (MP). MATERIAL AND METHODS: The diagnosis of MP was made in
      75 patients at echocardiography. ECG monitoring was made and the study of the
      ability of blood lymphocytes to produce IFN-gamma (If-g). RESULTS: The ability to
      produce If-g was diminished. This phenomenon is associated with chronic
      inflammation, autonomic disregulation of cardiac activity, depends on gender.
      CONCLUSION: Cytokine modulates metabolism of connective tissue in MP so If-g may
      participate in MP pathogenesis. Therefore, If-g and/or its inductors may prevent
      some MP-related complications due to its deficiency.

PMID- 16281496
TI  - [Long-term prognosis in patients with rheumatoid arthritis depending on baseline
      variability of cardiac rhythm].
AB  - AIM: The study of outcomes of rheumatoid arthritis (RA) depending on cardiac
      rhythm variability (CRV). MATERIAL AND METHODS: A total of 78 patients with RA of
      I--III degree of activity aged 38-83 years (mean age 60.3 +/- 10.8 years) were
      examined using 24-h AP and ECG monitoring. Follow-up was 2-4 years. RESULTS: A
      clear correlation was seen between RA activity and CRV. CONCLUSION: In patients
      with high activity of RA, CRV decline reflect severity of inflammation. In low RA
      activity, low CRV may point to the presence of IHD. Low CRV in RA activity of
      degree I-II may indicate high risk of sudden cardiac death and acute myocardial
      infarction within 2-4 years.

PMID- 16281497
TI  - [Heart affection in patients with ankylosing spondiloarthritis].
AB  - AIM: To study features of heart disease in patients with alkylosing
      spondyloarthritis (ASA). MATERIAL AND METHODS: We examined 56 ASA patients. Most
      of the examinees had spinal problems, moderate activity, x-ray sacroileitis stage
      III. RESULTS: Pulmonary hypertension was detected in 60.7%, right ventricular
      (RV) hypertrophy--in 37.5%, RV dilation--in 30.4% patients. Interventricular
      septum, left ventricular posterior wall were thickened (p < 0.05). Left
      ventricular diastolic dysfunction was registered in 18.2% ASA patients. The
      changes correlated with the disease duration, spinal lesion, especially of
      thoracic part. CONCLUSION: Pulmonary hypertension is a frequent finding in ASA
      patients. Echocardiography (ECG) is highly informative in detection of pulmonary
      hypertension and right heart disorders in ASA patients. ECG is a screening method
      in diagnosis of pulmonary hypertension in ASA patients.

PMID- 16281498
TI  - [Microalbuminuria--an independent indication for administration of ACE
      inhibitors: role of fosinopril (PREVEND IT trial)].

PMID- 16281499
TI  - [Endothelin aggression in pathogenesis of chronic cardiac failure and approaches
      to its therapeutic correction].

PMID- 16281500
TI  - Global status of immunization safety: report based on the WHO/ UNICEF Joint
      Reporting Form, 2004 update.

PMID- 16281501
TI  - [Expressions of telomerase reverse transcriptase and vascular endothelial growth
      factor and their correlation in prostate cancer].
AB  - OBJECTIVE: To investigate the expressions of telomerase reverse transcriptase
      (TRT) and vascular endothelial growth factor (VEGF) and their correlation in
      prostate cancer (PCa). METHODS: TRT and VEGF expressions were assayed in 30 cases
      of PCa and 30 cases of benign prostatic hyperplasia (BPH) by means of
      immunohistochemistry (SP) combined with computer assisted image analysis.
      RESULTS: The expression of TRT was detected in 19 of the 30 cases of PCa and 5 of
      30 cases of BPH, and that of VEGF in 23 of the 30 PCa and 14 of the 30 BPH
      patients. TRT and VEGF expressions were significantly higher in cancer tissues
      than in BPH (P < 0.05). A significant correlation was observed between TRT and
      VEGF expressions (r = 0.8333, P < 0.05). CONCLUSION: The expression of TRT or
      VEGF might be a malignant phenotype in PCa. The expression of TRT is
      significantly correlated with that of VEGF, but the mechanisms are yet to be
      further studied.

PMID- 16281502
TI  - [Expression and significance of the matrix metalloproteinase inhibitor RECK gene
      in prostate cell strains].
AB  - OBJECTIVE: To investigate the expression and significance of RECK gene and MMP-9
      in prostate cell strains such as BPH-1, DU45, LNCaP and PC-3. METHODS: The
      expression of mRNA of RECK and MMP-9 was measured by RT-PCR and RECK protein was
      evaluated by Western blot. RESULTS: The mRNA level of the RECK gene in the
      prostate carcinoma cell strains, such as DU45, LNCaP and PC-3, was lower than
      that in the benign prostate hyperplasia cell line BPH-1, while MMP-9 had a higher
      expression. The protein level of RECK in DU-45, LNCaP and PC-3 was lower than
      that in the BPH-1. CONCLUSION: The RECK gene is supposed to be a kind of tumor
      suppressor gene, which may act by inhibiting the activity of MMP-9.

PMID- 16281503
TI  - [Identification of response element gene sequence for non-steroid hormone
      transcription factors for the activation and up-regulation of L-plastin
      expression in prostate cancer].
AB  - OBJECTIVE: To search and identify the non-steroid receptor binding cis-acting
      elements in the L-plastin promoter in prostate cancer, and the correlative
      regulation pathway and transcription factors. METHODS: On the basis of
      construction of the L-plastin promoter luciferase vectors which were removed the
      steroid hormone receptor AR and ER binding elements, the promoter on the vector
      was nest-deleted by Exonuclease III and the relative luciferase plasmids were
      constructed. Transfected these twelve plasmids into prostate cancer cell line
      LNCaP under dihydrotestosterone-stimulated situation or not and test the
      intensity of luciferase, then we got the regulation message of every 200 bp part
      of the promoter in prostate cancer. After the analysis of relative programme, we
      got the possible regu- lation pathway of non-steroid hormone transcription
      factors. After removing the possible transcription factors binding site sequence
      by site-specific mutagenesis, the changes luciferase of activities proved our
      reasoning. RESULTS: We succeed in segmental deletion of the L-plastin promoter,
      and constructing the relative plasmids containing part L-plastin promoter on
      luciferase vector pGL3-basic. After testing the luciferase activities of
      constructed plasmids, we found the sequence from 206 to 1 of L-plastin promoter
      had significant luciferase activity. The software TRANSFECT showed that there
      were binding elements for transcription factors AP-4 at seq-198 to 192 and SP-1
      at seq-54 to 41 on the short part promoter (206 to 1). The recombinant plasmids
      deleted the AP-4 and SP-1 binding elements had lower luciferase activity than the
      wild-type. CONCLUSION: There are some other non-steroid hormone pathway to
      regulate the expression of L-plastin except the steroid hormone pathway in
      prostate cancer. The main binding sites of the non-steroid hormone regulator lies
      in the sequence from 206 to 1. Transcription factors AP4 and SP-1 may up
      regulated the expression of L-plastin by binding these sites.

PMID- 16281504
TI  - [Changes of cycle and apoptosis of spermatogenic cells and antioxidant capacity
      in male rats with diabetes mellitus].
AB  - OBJECTIVE: To explore the changes of cycle and apoptosis of spermatogenic cells
      and antioxidant capacity of the serum and testis in male rats with diabetes
      mellitus. METHODS: Thirty male rats were divided into two groups, 10 for normal
      control and 20 for the diabetes group. The rats were injected intraperitoneally
      with streptozocin (TZ) to develop diabetes, and 12 weeks later, their survival
      rate and testis weight were recorded. The percentage of G0/G, S and G2/M phases
      and apoptosis in spermatogenic cells were measured with flow cytometry (FCM).
      Malondialdehyde (MDA) and nitric oxide (NO) levels, superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px) and NO synthase (NOS) activities in the serum and
      testis were measured with thiobarbituric acid reactive substances (TBARs), nitric
      acid reoxidized enzyme, xanthine oxidative enzyme, 5,5 Dithiobis (2,2
      nitrobenzoate) (TNB) and visible light photometer methods, respectively. RESULTS:
      Twelve weeks after the male rats got diabetes, their survival rate, body weight
      and testis weight were significantly lower (p < 0.05), and the percentages of
      G0/G1 phases and apoptotic spermatogenic cells were obviously higher (P < 0.05)
      than the normal control. At the same time, the percentage of S and G2/M phases
      spermatogenic cells decreased. So the spermatogenic cells were arrested in G0/G1
      phase. In the diabetic rat serum and testis, especially in the testis, MDA levels
      were distinctly higher and SOD activities were significantly lower than those in
      the control. Serum GSH-Px activities of the diabetic rats were significantly
      lower (p < 0.05), while testis GSH-Px activities were significantly higher than
      those in control group (P < 0.01). NO contents in the serum and testis of the
      diabetic rats (P < 0.01) increased significantly, particularly the former, while
      NOS activities in the serum decreased significantly as compared with the control
      (P < 0.5). CONCLUSION: The increase in testis and serum MDA levels and NO
      contents and the decrease in the antioxidant enzyme activity of the diabetic rats
      may be relevant to spermatogenic disorder caused by the increase of G0/G1 phases
      arrest and spermatogenic cells apoptosis.

PMID- 16281505
TI  - [Experimental study of changes in microscopic characteristics and ability of
      secreting testosterone of aged SD rat leydig cells].
AB  - OBJECTIVE: To research the changes in microscopic characteristics and ability of
      secreting testosterone between aged SD rat Leydig cells and young SD rat Leydig
      cells. METHODS: The total and free serum testosterone levels of serum both young
      and aged rats were examined. The changes in microscopic characteristics between
      young and aged rat Leydig cells were observed under microscope and electron
      microscope. The testosterone secreted by cultured Leydig cells of stimulated by
      hCG and Forskolin both groups were detected. RESULTS: A significant difference
      was found in both total and free testosterone levels between young and old rats
      (P < 0.05). Aged SD rat Leydig cells were observed smaller in volume and more
      markedly stained than young ones; The secretion ability of aged rat Leydig cells
      was found lower than that of young rat Leydig cells with or without hCG and
      Forskolin stimulation (P < 0.05). CONCLUSION: The secreting index of aged SD rat
      Leydig cells is lower than that of young rat Leydig cells both in vivo and vitro,
      and the reason is the system of synthesizing testosterone is arrested.

PMID- 16281506
TI  - [Survey on reproductive health status of Shanghai college students].
AB  - OBJECTIVE: To explore reproductive health condition of college students in
      Shanghai and provide scientific basis for reproductive health education. METHODS:
      From July 2004 to March 2005, 1192 college students (majors including medicine,
      science and engineering, arts and culture; 618 medical students and 549 non
      medical; 555 male and 612 female) from seven time-day colleges in Shanghai were
      investigated with a reproductive health questionnaire involving sex. The
      questionnaire was constituted by 72 topics, involving the need of education, sex
      attitude, sex videos, sex hygiene knowledge and sexually transmitted diseases
      (STDs), etc. RESULTS: 39.33% (459/1167) students thought they had accepted formal
      sex education; 49.19% (574/1167) students chose lecture as the favorite way;
      41.90% (489/1167) students thought the reproductive health education would not
      increase the incidence of premarital sexual behavior; 64.10% (748/1167) students
      thought it was necessary to give college students reproductive health
      instructions and knowledge. On the other hand, we found 45.05% (250/555) boys and
      27.45% (168/612) girls could accept the premarital sexual behaviors; 35.32%
      (196/555) boys and 39.38% (241/612) girls could accept premarital pregnancy;
      44.39% (518/1167) students could calculate the safe period accurately; 71.38%
      (833/1167) students knew emergency contraception measures; 57.67% (673/1167)
      students knew how to and when to use condoms; To our surprise, only 2.19%
      (12/549) non-medical students and 12.14% (75/618) medical students knew exactly
      the whole 4 sexually transmitted diseases that needed to be essentially prevented
      in China. CONCLUSION: At present, the reproductive health condition of college
      students in Shanghai is sophisticated. Much more education on sex safety, self
      protection skills and acquired immunodeficiency syndrome (AIDS) knowledge, etc
      should be reinforced.

PMID- 16281507
TI  - [Expression of nerve growth factor in cavernous tissue and its effects on the
      treatment of rats with diabetic erectile dysfunction].
AB  - OBJECTIVE: To investigate the content of nerve growth factor (NGF) in penis of
      rats with diabetic erectile dysfunction (DED) and apply rhNGF to treat the DED
      rat model to study the pathogenesis mechanism of DED and treatment effects by NGF
      for DED rat model. METHODS: Fifty adult male SD rats were randomly selected to
      make up diabetic models. After 8 weeks, the mRNA and protein levels of NGF in rat
      penis were detected. Then the rest of rats were divided into 5 groups: normal
      control group, non-treated diabetes group, NGF treatment group, insulin treatment
      group, NGF plus insulin treatment group. After 8 weeks of treatment,
      intracavernous pressure (ICP) was measured. The content of neuronal nitric oxide
      synthase (nNOS) in the erectile tissue was also value- ated by
      immunohistochemistry staining. RESULTS: Compared with those of normal control
      group, the mRNA content of NGF and protein in the penis of non-treated diabetic
      rats is increased significantly. Compared with non-treated diabetic group, ICP
      was much higher in the treated groups which received NGF or/and insulin therapy,
      and the changes in nNOS staining of those groups were the same. CONCLUSION: The
      injury of pelvic splanchnic nerves in advanced stage of diabetes may lead to DED,
      which may be relevant to the abnormal of NGF level or the NGF receptors. The
      increased extent of NGF in penis of rat with DED suggests that erectile nerves be
      severely damaged by diabete and the increase of producing NGF couldn't compensate
      the needs for reproduction of the nerve fibers. The ability of combination of NGF
      with its receptor may also be damaged. It is helpful to use exogenous NGF to
      lessen the partly neuropathy and improve the erectile dysfunction of diabetic
      rats. The abnormal of NGF may play an important role in the pathogenesis of
      diabetic ED and its treatment.

PMID- 16281508
TI  - [Study on the knowledge of and attitude to sexual dysfunction in aged men].
AB  - OBJECTIVE: To investigate the knowledge of and attitude to sexual dysfunction in
      aged men, and to discuss the status and needs of male healthcare. METHODS: Two
      thousand seven hundred and twenty-eight men (40-70 years old) were surveyed on
      sexual dysfunction using the randomized questionnaire in Xicheng District,
      Beijing. RESULTS: The prevalence of erectile dysfunction (ED) was 41.2%, and only
      12.1% ED patients were to see the doctor. 52.4% aged men thought the sexual life
      was important or very important during the life, and 55.6% thought ED would exert
      negative impact on the quality of life and the partner relationship. Although
      27.4% knew that ED was a kind of disease, 49.0% thought ED was a nature rule.
      Compare to the 41.2% ED prevalence, only 9.7% male were dissatisfied with their
      sexual life, and later ratio was 14.1% among the partner. CONCLUSION: In China,
      the status of the knowledge of and attitude to sexual dysfunction in aged men was
      unsatisfactory to some extent. There is a lot of work to do especially in sexual
      healthcare education and improvement on diagnostic and treatment of sexual
      dysfunction.

PMID- 16281509
TI  - [Specific expression of beta-actin during spermatogenesis in rats].
AB  - OBJECTIVE: To screen the stage-specific expression proteins during rats
      spermatogenesis, and to investigate the beta-actin expression and localization in
      the tissues of rat testicular. METHODS: Highly enriched type A spermatogonia,
      pachytene spermatocytes and round spermatids were isolated by STAPUT method
      (sedimentation velocity at unit gravity, with 2% - 4% BSA gradient in DMEM/F12
      medium) respectively to get the total proteins. The difference of protein
      expression between the three kinds of cells was analyzed by two-dimensional
      electrophoresis. Then the distribution of beta-actin in rat testicular tissues
      was investigated using specific anti-beta-actin antibodies by immunohistochemical
      method. RESULTS: beta-actin was identified as a stage-specific expression protein
      by two-dimensional electrophoresis. beta-actin protein was more strongly
      expressed in type A spermatogonia and pachytene spermatocytes, but not in round
      spermatids. The immunohistochemical results showed that beta-actin was mainly
      located in the cytoplasm of type A spermatogonia and pachytene spermatocytes and
      in the nuclei of nearly mature spermatids. CONCLUSION: beta-actin protein is a
      stage-specific expressed protein and may play an important role in
      spermatogenesis.

PMID- 16281510
TI  - [A controlled randomized trial of the use of combined L-carnitine and acetyl-L
      carnitine treatment in men with oligoasthenozoospermia].
AB  - OBJECTIVE: To determine the efficacy and safety of combined L-carnitine and
      acetyl-L-carnitine therapy in infertile males with oligoasthenozoospermia.
      METHODS: One hundred fifty patients with oligoasthenozoospermia were randomized
      selected into treatment and control groups. The treatment group with 90 patients
      were given L-carnitine (2 g/d) and acetyl-L-carnitine (1 g/d) orally, twice a
      day. The patients in control group were given Vitamin E 100 mg plus Vitamin C 100
      mg, tid. The oral therapy lasted three months and patients accepted sperm
      analysis every one month. The L-carnitine level in seminal plasma was examined by
      high performance liquid chromatography (HPC). Side effects as well as pregnant
      rate were observed. RESULTS: In the treatment group, 85 patients out of 90
      finished the three month treatment. Female spouses of 10 patients (11.6%)
      achieved pregnancy. Moreover, their forward motile sperm per ejaculation, total
      motile sperm, as well as the concentration of L-carnitine in seminal plasma were
      increased significantly (P < 0.01). In control group, 53 patients out of 60
      completed three months therapy. Two pregnancy (3.7%) was observed. Though some
      increase was seen in number of forward motile sperm and total motile sperm per
      ejaculation, the changes were not statistically significant (P > 0.05). The
      difference of the pregnant rate between two groups was statistically significant.
      No side effects were found. CONCLUSION: Combined treatment with L-carnitine and
      acetyl-L-calmitine can be an effective and safe option for treating
      oligoasthenozoospermia by means of significantly improving forward motile sperm
      and total motile sperm per ejaculation, as well as increasing pregnant rates.

PMID- 16281511
TI  - [Diagnosis and differential diagnosis of Kallmann syndrome].
AB  - OBJECTIVE: To study diagnosis and differential diagnosis of Kallmann syndrome.
      METHODS: The examinations including routine karyotyping, sex hormone, GnRH
      stimulation test and MRI were performed. RESULTS: Cytogenetic analysis of his
      peripheral lymphocyte by G banding showed a normal male karyotype. GnRH
      stimulation test presented a good reaction. Plasma levels of luteinizing hormone
      (LH), follicle-stimulating hormone (FSH) and testosterone were very low. Absent
      olfactory bulb was found by magnetic resonance imaging (MRI). CONCLUSION:
      Karyotype analysis, sexual hormone, GnRH stimulation test and MRI are very
      important the diagnosis of Kallmann syndrome.

PMID- 16281512
TI  - [The results of surgery on HIV carriers with urinary system disease].
AB  - OBJECTIVE: To approach characteristics of performing operation on HIV carriers
      with urinary system diseases. METHODS: To summarize author's experiences of
      surgery on 41 HIV carriers suffering urinary system diseases abroad from April
      1996 to May 2004. RESULTS: The 41 HIV carriers received HAART and were performed
      with corresponding operations, followed up from 4 to 30 months post-operatively.
      The 31 carriers have recovered well up to date, while 4 carriers died of AIDS.
      Among them, 2 patients with penis cancer who received a partial peotomy and a
      patient with renal tuberculosis receiving left nephrectomy were died of AIDS
      within 4-8 months after operations whose CD4+ T lymphocyte number was below 0.2 x
      10(9)/L. CONCLUSION: Prior to operation, HIV carriers should receive HAART
      ordinarily to control copy of the virus. The CD4+ T lymphocyte number is
      important for selecting a proper time for operation and deciding the further
      after surgery. We also take note to CD4+ T lymphocyte number to monitor progress
      of the AIDS. For those HIV carriers, endourologic surgery and laparoscopy should
      be taken so far as possible. Meanwhile, medical stuffs must pay more attention to
      preventing occupational infection during surgery.

PMID- 16281513
TI  - [Long term survival results in advanced prostate cancer treated with combined
      androgen blockade].
AB  - OBJECTIVE: To understand long-term survival rate after combined androgen blockade
      (CAB) in patients with advanced prostate cancer. METHODS: A selected population
      of 59 patients with advanced prostate cancer were treated with CAB. 28.81%
      (17/59) of patients had clinical locally advanced disease (stage T3-4N0M0), and
      45.76% (27/59) of patients had metastatic disease (stage TxNxM+). Overall,
      patients were followed for a median of 62 (range 6-136) months. RESULTS: Of the
      59 patients with advanced prostate cancer, 3-year, 5-year and 7-year overall
      survival rates were 79.36%, 61.46% and 49.15%, respectively. The 5-year survival
      rate were 80.77% and 32.65% for clinical locally advanced disease and metastatic
      disease. Specifically, men with poorly differentiated prostate cancer had a 5
      year survival of only 30% when compared with men with well-differentiated
      prostate disease who had a 5-year survival of 86.21%. CONCLUSION: Based on these
      findings, men with poorly differentiated cancer, stage T3c-4NxMx or TxNxM+ and
      PSA level above 30 microg/L had a high probability of dying from their advanced
      prostate cancer.

PMID- 16281514
TI  - [The effect of double-balloon and triple-channel transurethral perfusion and
      drainage catheter on patient's sperm quality in the therapy of chronic
      prostatitis].
AB  - OBJECTIVE: To investigate the clinical improvement of patient's sperm quality
      after the therapy on chronic prostatitis (CP) with double-balloon and triple
      channel transurethral perfusion and drainage catheter. METHODS: Double-balloon
      and triple-channel transurethral perfusion and drainage catheter along with
      millimeter wave physical therapy and intravenous infusion with antibiotics were
      adopted to treat 58 CP patients. The patient's sperm quality was analyzed pre-
      and post- therapy by Computer-assisted Sperm Analysis Instrument. RESULTS: The
      comparison of patient's sperm quality parameters between pre- and post-therapy:
      percentage of motile sperm (42.66 +/- 17.12)% vs (55.23 +/- 14.79)%, grade a
      sperm (12.63 +/- 12.50)% vs (29.84 +/- 14.86)%, grade a + b sperm (29.14 +/
      15.04)% vs (42.28 +/- 12.67)%, amplitude of the lateral head displacement (ALH)
      (3.04 +/- 1.55) microm vs (2.69 +/- 1.67) microm. The differences between pre-
      and post-therapy in above mentioned sperm parameters were all statistically
      significant (P < 0.01). While the differences among other sperm parameters were
      not statistically significant (P > 0.05). CONCLUSION: Timely and effective
      therapy with transurethral perfusion and drainage catheter can improve the
      patient's sperm quality significantly, but sperm movement function cannot resume
      completely in a short time.

PMID- 16281515
TI  - [Effect of secretory human calcitonin gene-related peptide recombinant AAV on
      penile erection in streptozotocin-induced diabetic rat].
AB  - OBJECTIVE: To determine whether recombinant adeno-associated virus-mediated
      overexpression of hCGRP in the corpus cavernosum can affect the continuous
      production of hCGRP in the penile tissue and enhance erectile responses in STZ
      induced diabetic rats. METHODS: Diabetes mellitus was induced by a single
      intraperitoneal injection of 60 mg/kg streptozotocin in male SD rats. VssHGCMV
      hCGRP, VssCMV-GFP and rAAV solution were injected into the corporal cavernosum of
      STZ-induced diabetic rats, respectively. The corporal tissue was obtained from
      groups of 8 rats on day 5 post-injection, and the expressions of CGRP and GFP in
      cavernosal tissue were detected using immunohistochemistry and laser scanning
      confocal microscopy, respectively. Cavemosal tissue cAMP and cGMP levels were
      measured using radioimmunoassay. On day 5 post-injection, intracavernous pressure
      induced by electrostimulation of penile dorsal nerves was measured and recorded
      with a biological signal processing system in each group rat. RESULTS: rAAV
      transduction efficiency of GFP reporter gene was measured by laser scanning
      confocal microscopy and was observed in the penile tissue, especially in the
      corporal cavernosum and the vessel 5 days after transfection with VssCMV-GFP.
      Immunohistochemistry showed that the CGRP increased in the corporal cavernosum.
      In addition, both cAMP and cGMP levels in the corpora cavernosa transfected with
      VssHGCMV-hCGRP were significantly increased, compared with controls [(48.4 +/-
      6.5) nmol/L and (21.2 +/- 13.6) nmol/L vs (16.7 +/- 2.5) nmol/L and (0.42 +/-
      0.12) nmol/L, respectively]. More importantly, 5 days after administration of
      VssHGCMV-hCGRP,a significant increase was observed in the erectile response to
      penile dorsal nerve stimulation in the diabetic rat [(60.5 +/- 4.5) mm Hg vs (22.
      3 +/- 1.3) mm Hg]. CONCLUSIONS: This results demonstrate that rAAV-mediated
      transfer of the CGRP gene can increase production of endogenous CGRP, cAMP and
      cGMP in corpora cavernosa of STZ-induced diabetic rats. Moreover, overexpression
      of CGRP enhances ICP and the erectile response to penile dorsal nerve stimulation
      in the diabetic rat.

PMID- 16281516
TI  - [Current research on psychological hindrance in patients with chronic
      prostatitis].
AB  - Chronic prostatitis (CP) is a common and painful disease in young and middle-aged
      men, with its causes remaining confused. In recent years, in-depth studies have
      been made on the interaction between CP and psychological hindrance. This review
      focuses on the manifestation and the mechanism of psychological hindrance in CP
      patients as well as on the effect of psychological therapy, and is meant to offer
      some reference to the etiology and semiology studies of CP.

PMID- 16281517
TI  - [Effects of some micronutrients on partial androgen deficiency in the aging
      male].
AB  - With the step-up of the aging process, the increase of old population and the
      advance of living standard, China has already entered into the aged society.
      Problems on the health and life quality of the aging male have been receiving
      more and more attention from scientific researchers. Partial androgen deficiency
      in the aging male (PADAM) is a kind of syndrome which affects the aging male s
      health. At present, testosterone supplementation therapy is mostly used to
      improve the symptoms of PADAM, but it may bring some adverse effects, such as
      erythrocytosis and hyperplasia and carcinoma of the prostate. Some studies have
      shown that quite a few nutrients, especially vitamin A, vitamin E, zinc and
      selenium are favorably related to androgen deficiency and sperm production. This
      article discussed the effects of micronutrients on PADAM.

PMID- 16281518
TI  - [The relaxation effects of six extracts from Chinese herbs on the corpus
      cavernosum tissue of rabbit in vitro].
AB  - OBJECTIVE: To study the relaxants effects of six extractions from Chinese Herbs
      (neferine, tetrandrine, kakonein, scutellarin, ginsenoside Rgl and ginsenoside
      Rb1) on the corpus cavernosum tissue of rabbit in vitro. METHODS: Isolated
      stripes of rabbit corpus cavernosum tissue were precontracted with 10(-5) mol/L
      phenylephrine (PE). Relaxation in response to cumulative doses of six extracts at
      (10(-8) - 10(-3)) mol/L was determined. RESULTS: On rabbit cavernosal muscle
      stripes precontracted with PE, neferine, tetrandrine, kakonein and scutellarin
      showed dose dependent relaxation. IC50 values were 4.60 x 10(-6), 3.73 x 10(-5),
      8.03 x 10(-4) and 3.33 x 10(-3) mol/L, respectively. However, in the meantime, it
      was found that the relaxant effects of ginsenoside Rgl and ginsenoside Rbl less
      significant to stripes precontracted with PE. When the final concentration was
      10(-3) mol/L, the relaxations were only (16.32 +/- 5.45)% and (11.21 +/- 3.10)%.
      CONCLUSION: Among the six extracts which showed relaxant effects to rabbit
      cavernosal muscle stripes precontracted with PE, neferine had greater functions
      than the other five extracts.

PMID- 16281519
TI  - [From better erection to better sex: viagra updates 2005].
AB  - Viagra (sildenafil citrate) has been proven as the first choice of treatment for
      erectile dysfunction (ED) due to its producing rigid, sustained erection and
      rapid onset of action. In recent years, more and more studies on efficacy of
      Viagra focused on the improvement of overall sex life, as well as the
      psychological impact on the ED patients. Using several psychological assessment
      tools such as erectile dysfunction inventory of treatment satisfaction (EDITS),
      self-esteem and relationship (SEAR) questionnaire, psychological impact of
      erectile dysfunction (PIED) scores, these studies found that Viagra treatment
      significantly improved the following psychological factors: satisfaction of both
      ED patients and their partners with sexual intercourse and sexual relationship,
      confidence and self-esteem of the patients, desire for intimacy and sexual
      intercourse. The significant increased frequency of sexual intercourse attempts
      and improvement of health-related quality of life were also seen in the patients
      receiving Viagra treatment. Thus, Viagra produces the better erection and then
      promotes the better sex cycle.

PMID- 16281520
TI  - [Tattoo dyes, old and new].

PMID- 16281521
TI  - [Therapy options for psoriasis in childhood and adolescence].
AB  - Up to 30% of all psoriatic patients show their first symptoms during childhood
      and adolescence. In 1/4 of these children, psoriatic lesions appear within the
      first two years of life. The treatment of pediatric psoriasis differs
      considerably in several ways from that of adults. Not only the age and intensity
      but also physical development, prognostic criteria and social background should
      be considered. Standard procedures, clinical trials of high quality and
      therapeutic guidelines for psoriasis in childhood are still lacking. This review
      surveys the therapeutic management of pediatric and juvenile psoriasis. Current
      topical and systemic therapy options are critically reviewed. Prevention as well
      as enhancement of quality of life are also considered.

PMID- 16281522
TI  - [Randomized, placebo-controlled, double blind clinical trial for the evaluation
      of the efficacy and safety of oral methantheliniumbromide (Vagantin) in the
      treatment of focal hyperhidrosis].
AB  - BACKGROUND: Methanthelinium bromide is a quaternary ammonium derivate with
      anticholinergic activity. Since 1951 it has been used to treat patients with
      hyperhidrosis. However, all efficacy data has so far been limited to case reports
      and case series. We here report on the results of the first randomised clinical
      controlled trial on the efficacy and safety of methanthelinium bromide. PATIENTS
      AND METHODS: A total of 41 patients with a mean age (+/- standard deviation) of
      28 +/- 9.8 years (Range 18.7-54.8) were included, 31 (76%) of them were females.
      Main inclusion criteria were are focal hyperhidrosis of a one year or longer
      duration and a gravimetrically assessed sweat production of > or =50 mg/min.
      Patients were treated with 2 x 50 mg methanthelinium bromide or placebo orally
      daily for 4 weeks. The therapeutic effect was determined by repeated gravimetric
      measurement of sweat production and by recording the patients' degree of
      satisfaction. RESULTS: The efficacy was most pronounced for patients with an
      axillary hyperhidrosis of > or =50 mg/min (p = 0.02, chi2-test, two-sided). For
      the total group the main axillary sweat production decreased in the verum-treated
      arm from a mean value of 89.2 +/- 73.4 mg/min prior to therapy to 53.3 +/- 48.7
      mg/min during therapy (p = 0.02, Wilcoxon test, two-sided). In contrast, no
      difference was detected in the placebo arm with 60.7 +/- 42.8 mg/min prior to and
      59.1 +/- 40.6 mg/min during therapy (p = 0.92, Wilcoxon test, two-sided). For the
      palmar sweat production no difference between the verum- and the placebo-treated
      group was found. No serious adverse events were reported. As expected, dryness of
      the mouth, a known adverse reaction of anticholinergics, was reported
      significantly more frequently in the verum-treated arm. CONCLUSIONS:
      Methanthelinium bromide has been considered for many years as a therapeutic
      option for the treatment of focal hyperhidrosis. However, its efficacy and safety
      have not previously been investigated in controlled randomised studies. We
      demonstrated both a decline in axillary sweat production and good tolerance.
      Therefore, the treatment of axillary hyperhidrosis with methanthelinium bromide
      in a regimen of 50 mg twice daily can be recommended, especially in those cases
      which are refractory to topical treatment with for example aluminium chloride
      hexahydrate solution. In contrast, we found no evidence for a clinically relevant
      diminution of palmar sweating.

PMID- 16281523
TI  - [Elemental analysis of tattoo dyes-is there a potential risk from tattoo dyes?].
AB  - BACKGROUND: Tattoo dyes in current use can cause foreign body reactions. METHODS:
      There are no rules regulating the composition of tattoo dyes. We performed
      elemental analysis on a series of dyes obtained from tattoo studios to determine
      if any dangerous materials were present. The composition of the dyes was
      determined using scanning electron microscopy in combination with energy
      dispersive X-ray microanalysis (EDS). This technique demonstrates bets the
      presence of elements of the sodium family and proves the presence of various
      metals. It provides no insight in chemical structures or bonds. RESULTS:
      Elemental analysis revealed multiple metallic components in the dyes; these
      materials may be responsible for persistent foreign body reactions even years
      after being placed in the skin. Silicon, aluminium, titanium and copper were
      found in various yellow, green and red dyes. The composition of various dyes of
      the same colour from different sources was highly variable. CONCLUSIONS: The
      tattoo dyes currently in use contain a number of components which cannot be
      regarded as "tissue inert". Chronic foreign body reactions can be expected even
      after many years.

PMID- 16281524
TI  - [Treatment of pemphigus vulgaris with high-dose intravenous immunoglobulins in a
      patient with steroid-induced osteonecrosis of the femoral head].
AB  - High-dose immunoglobulins (IVIG) are important agents in the treatment of
      numerous autoimmune disorders. In the field of dermatology, increasing numbers of
      patients with bullous autoimmune disorders and mixed connective tissue diseases
      have been treated. We successfully treated a patient with pemphigus vulgaris with
      IVIG, after he had developed osteonecrosis of his right femoral head while on
      azathioprine and corticosteroids. After reduction of oral corticosteroids, his
      disease flared dramatically. The addition of a high dose immunosuppressive
      regimen including azathioprine and dapsone failed to help. Thus high dose IVIG (2
      mg/kg, 4 weeks interval) therapy was initiated and induced complete healing of
      the skin lesions. The clinical improvement and the titer of the relevant
      autoantibodies against desmoglein 3 and desmoglein 1 showed correlation.

PMID- 16281525
TI  - [Acute juvenile pityriasis rubra pilaris in a 2-year-old child].
AB  - Pityriasis rubra pilaris (PRP) is a rare idiopathic erythematosquamous disorder.
      Griffiths proposed five clinical and prognostic forms: (1) classic adult, (2)
      atypical adult, (3) classic juvenile, (4) circumscribed juvenile and (5) atypical
      juvenile. A 2 1/2 year old boy presented with type 3 PRP; as is typical, the skin
      eruption was preceded by an infectious disorder. Although type 3 PRP normally
      shows spontaneous resolution after several months to years, our young patient had
      a severe and protracted course, only responding to systemic retinoids.

PMID- 16281526
TI  - [Heat shock proteins in dermatology].

PMID- 16281527
TI  - [Cobbled aggregated moles with coarse nodes in a 49-year old woman].

PMID- 16281528
TI  - [Erythemic swelling of the upper arms, leukocytosis, and CRP elevation in a 78
      year old woman].

PMID- 16281529
TI  - [Actinic prurigo].

PMID- 16281530
TI  - [Prof. Dr. Med H.-J. Vogt on his 70th birthday].

PMID- 16281532
TI  - Make promises a reality.

PMID- 16281531
TI  - [Smoking--effects on the skin: a case for an alternate characterization].

PMID- 16281533
TI  - More losers than winners from Agenda for Change.

PMID- 16281534
TI  - Live and let go.

PMID- 16281535
TI  - The ethical divide.
AB  - Ethics is an area of growing interest in nursing and is a compulsory part of
      nurse education. Yet record numbers of nurses care being removed from the
      register and media stories of poor practice are rife. This article explores the
      issues. Ethics is about how we ought to behave towards one another. Ethics can be
      seen as elitist and too theoretical, failing to bridge the theory-practice gap.
      Discussion of ethics in health care tends to concentrate on issues with a 'gee
      whizz' factor. Health care is a moral enterprise and, therefore, nursing has
      moral ends.

PMID- 16281537
TI  - Looking for someone to blame.

PMID- 16281536
TI  - Breathe easy.
AB  - Empowering patients to manage their own asthma needs a time commitment from
      nurses but pays dividends in terms of symptom control and patients' quality of
      life. Asthma management plans need to be tailored to individual patients. Active
      management of the condition can reduce hospital admissions, visits to A&E, GP
      visits and days off work. Patients need simple messages to manage their own
      asthma. Adjustable dosing results in better asthma control and less use of
      medication.

PMID- 16281538
TI  - Stride forth with poles.

PMID- 16281539
TI  - Psychiatry: the career of choice.

PMID- 16281540
TI  - Core nursing values brought to life through stories.
AB  - AIM: To determine what contributes to the professional fulfilment of registered
      nurses. METHOD: An interpretive research approach was used to gather data from a
      large international sample of nurses from a variety of nursing specialties. A web
      based data-collection method was developed to solicit and receive submissions.
      FINDINGS: Nurses who believed they provided high quality care and made strong
      connections with patients were usually very satisfied with their careers.
      CONCLUSION: Nurses who become well satisfied with their career choice live out
      their core values and engage in interdependence. They entwine themselves in a
      mutually dependent way with patients, learning and growing together as they share
      the journey through the care trajectory.

PMID- 16281541
TI  - Obtaining and communicating information about genetics.
AB  - This article, the last in this series, focuses on the ways a nurse can acquire
      relevant genetic information for effective practice and how this information can
      be communicated successfully.

PMID- 16281542
TI  - Infection rislks associated with urinary catheters.
AB  - Urinary catheterisation can kill. It is one of the most common healthcare
      interventions but carries the risk of 'significant danger' to patients from
      infection (Pratt et al 2001). While essential for some patients, this invasive
      procedure is sometimes unjustified and even forgotten once in place (Saint et al
      2005). Accountability for the safe management of urinary catheters by using
      evidence-based guidelines is emphasised. New ways of examining practice and
      planning for improvement (Department of Health 2005), and new technology (Tambyah
      2004) will contribute to better outcomes for those patients for whom the
      procedure is essential.

PMID- 16281543
TI  - Resuscitation trolley.

PMID- 16281544
TI  - The management of patients' pain in wound care.
AB  - This article raises professional awareness of patients' experiences of pain at
      wound dressing change, and provides nurses with practical strategies that enable
      them to minimise the pain and trauma experienced by patients during wound care
      procedures.

PMID- 16281545
TI  - Pressure ulcer risk in the peri-operative environment.
AB  - Every patient attending the operating theatre will at some stage be at risk of
      developing a pressure ulcer. Some of the important issues associated with
      pressure ulcer risk in the peri-operative environment are discussed. There are
      gaps in the knowledge base and a need for further research. These factors should
      be taken into account by peri-operative nurses in the care of surgical patients.

PMID- 16281546
TI  - Mind mapping.

PMID- 16281547
TI  - Study support.

PMID- 16281548
TI  - The truth about failure.

PMID- 16281549
TI  - [Preliminary study on bacterial diversity in a hot spring by using culture
      independent approach].
AB  - Bacterial biodiversity of the hot spring Dagunguo in Tengchong Rehai in Yunnan
      Province, China was preliminarily studied with culture-independent method. Five
      complete 16S rDNA sequences were obtained and phylogenetically analysed. Four of
      these sequences were closely related to the genera: Bacillus, Hydrogenobacter and
      Pseudomonas, and the other one was clustered with the Family
      Thermodesulfobacteriaceae between an unpublished genus Geothermobacterium and
      Thermodesulfobacteria. The V8 high variable region(about 600bp) of 16S rDNA from
      the five 16S rDNA sequences and the genomic DNA were obtained by PCR. All of the
      PCR products were run DGGE. The pattern of DGGE and the phylogenetic tree of the
      five sequences not only indicated the hot spring Dagunguo of Yunnan province has
      plenty of bacterial species but also showed they were dominant bacterial species
      in the hot spring.

PMID- 16281550
TI  - [Sequence analysis of NS1 gene of some H9N2 subtype influenza viruses isolated
      from chickens in China].
AB  - The nonstructural protein (NS1) genes of eight H9N2 subtype influenza virus
      strains isolated from diseased chickens on different farms during 1996 - 2001
      were amplified and sequenced. The nucleotide and deduced amino acid sequences of
      NS1 genes of these isolates were compared. The results showed that the homologies
      of nucleotide and amino acid of the isolates were 96.5% - 99.5% and 94.5 - 98.6%,
      respectively. These indicated that NS1 genes of H9N2 influenza viruses isolated
      in China were well conserved. Comparison of the amino acid sequences of NS1 genes
      of these isolates with those of H9N2 viruses isolated in Hong Kong of China,
      Korea and Pakistan demonstrated that nonstructural (NS1) proteins of the eight
      strains had a deletion of 13 amino acid residues at the carboxy terminus.
      Phylogenetic analyses showed NS1 genes of these isolates belonged to the same
      lineage and derived from an early chicken H9 virus isolated in 1994. The NS1
      genes of the eight isolates belong to different sublineages from those of the
      H9N2 viruses isolated in Hong Kong, Korea and Pakistan, suggesting that the
      geographical distribution plays a significant role in the evolution of the H9N2
      subtype influenza viruses.

PMID- 16281551
TI  - [Construction of genetic engineering microogranism of salt tolerant degrading
      strain].
AB  - H1 ( Halomonas sp.) was a strain of salt tolerance (18% NaCl, W/V) and degrading
      phenylacetic acid, plasmid pDT3 was a derivation of pUC19 inserted mpd gene
      (methyl parathion degrading gene), which is obtained from methyl parathion (MP)
      degrading strain DLL-E4 (Pseudomonas putida). Recombinant plasmids pKT-MP and
      pBBR-MP were constructed by inserting Hind III fragment (which include whole mpd
      gene) of pDT3 into broad host vector pKT230 and pBBR1-MCS2. With the aid of help
      plasmid pRK2013, pKT-MP and pBBR-MP were transferred into H1 (called tri-parent
      conjugation) and multi-functioned GEMs H-pKT-MP and H-pBBR-MP were constructed,
      which were salt tolerant, phenylacetic acid-degrading and MP-degrading. The
      activity of MP hydrolase of H-pBBR-MP and H-pKT-MP was 1 x and 2 x the one of DLL
      E4. The MP hydrolase activity of two GEMs were constant.

PMID- 16281552
TI  - [Codon optimization and expression in Pichia pastoris of E2 gene of classical
      swine fever virus].
AB  - Codon bias was one of the important parameter which influence heterogenous gene
      expression, optimizing codon sequence could improve expression level of
      heterogenous gene. In the preview study, wildtype E2 gene was expressed poorly in
      Pichia pastoris, in order to improve the expression level of E2 gene in Pichia
      pastoris, the low usage codons of E2 gene were mutated into high usage codons in
      Pichia pastoris by directed-mutagenesis based on PCR. The result showed that,
      compared with the results reported in preview study, the expression level of E2
      gene in Pichia pastoris was improved observably by substituting 24 low usage
      codons of E2 gene for the high usage synonymous codons. It suggested the stragety
      to improve the expression of E2 gene in Pichia pastoris by codon optimization was
      successful.

PMID- 16281553
TI  - [Relativity betweeen expression level of potato virus X coat protein and the
      codon usage of wobble codon].
AB  - The relationship between the quantities of rare codons and the expression levels
      of foreign genes is very important in gene engineering. But up to now, there is
      few experiment on it in multi-cellular eukaryotes, especially in plants. To study
      the effect of rare codons on the expression level of potato virus X (PVX) coat
      protein (CP) in transgenic tobacco, some preferred codons in PVX coat protein
      gene were substituted with synonymous rare codons without changing the encoded
      amino acid sequence using site-specific mutation. The modified coat protein gene
      (cpm) and non-modified coat protein gene (cpw) were inserted into binary vector
      under the control of CaMV35S promoter, and these two plant expression constructs
      were transferred into tobacco (Nicotiana tabacum cv. Xanthi) genomes via
      Agrobacterium mediated method and transgenic plants were generated. Western blot
      and ELISA of these transgenic tobaccos showed that the expression level of
      modified CP is about one third to one sixth of that of non-modified CP. Northern
      blot analysis of RNAs from some transformants indicated that the transcriptional
      levels of cpm are the same as that of cpw, which implicated that the quantity of
      rare codons in foreign gene was a possible limited factor in foreign gene
      expression process. Changing the quantity of rare codons maybe an effective
      method for organism to control gene expression.

PMID- 16281554
TI  - [Sequence aanlysis of intergenic region of rice stripe virus RNA4: evidence for
      mixed infection and genomic variation].
AB  - The intergenic region (IR) of the RNA4 of 22 isolates of Rice stripe virus (RSV)
      in China was cloned and sequenced. The IR sequences were compared with one
      another and with that from Japan. Sequence comparisons showed that these isolates
      could be divided into three different types, with the IR length of 634 bp, 654 bp
      and 732 bp, respectively. It is interesting to note three different types all
      occurred in Yunnan RSV natural population, whereas other province only existed
      654 bp type length isolates. Mixed infections with different types of IR length
      coexisting in some isolates in Yunnan was observed. IR sequences were not more
      conserved (83% - 100%) among the populations of RSV from China than with those of
      RSV isolates from Japan (83% - 94%). There were two important structure
      characteristics in IRs sequences. Firstly, there was a-19 nt insertion in 654 bp
      type isolates and a-103 nt in 732 bp type isolates in comparison to 634 bp type
      isolates. This inserted sequences were rather highly conserved. Blast analysis
      indicates the 16 nt (AGAAACATGAGAGTA) in 19 nt insertation was very similar in
      sequence to wheat cDNA library; and the 20 nt (AGAATTGCCTTGGTGTTAT) in 103 nt
      insertion was identical to a stretch sequences of barley cDNA library.
      Recombination hot-spot sequences existed in RNA4 IR. Secondly, IRs sequence was
      rich in U and A residues where two distant hairpin structures could be formed
      with computer-assisted folding analysis. One was highly conserved and stable, but
      the other was rather unstable because of bases variation. It is believed that
      this stabilised hairpin structure, rather than a sequence motif, might serve as a
      transcription terminator during the synthesis of mRNAs from the ambisense
      segments. Negative selection constraints imposed by secondary structure might
      have maintained the conserved sequences. In this paper, the relationship between
      the lowest free energy of the unstable hairpin structures and the different
      pathogenesis among some isolates was also discussed in this paper.

PMID- 16281555
TI  - [Integration and expression of beta-endoglucanase I from Trichoderma reesei in
      brewing yeast].
AB  - An integration plasmid pA15-PET for expression and secretion of beta
      Endoglucanase I (EG I ) in yeast was constructed by insertion of EG I cDNA
      between yeast alcohol dehydrogenase promoter and terminator region. The plasmid
      contained part of yeast rDNA sequence, which was used as a homologous fragment
      for integration. The EG I cDNA was introduced into an engineered brewing yeast
      BE9711 containing alpha-acetolactate decarboxylase (alpha-ALDC) encoding gene and
      integrated onto its rDNA sequence of chromosomal DNA by co-transformation of pA15
      PET and a YEP type plasmid pA15TXR carrying G418 resistance. The stable
      engineered brewing yeast expressing intracellulase alpha-ALDC and extracellular
      EG I simultaneously were obtained.

PMID- 16281556
TI  - [Expression of phosphofructokinase gene from Escherichia coli K-12 in obligately
      autotrophic bacterium Acidithiobacillus thiooxidans].
AB  - A plasmid pSDK-1 containing the Escherichia coli phosphofructokinase-1 (EC 2.7.1.
      11) gene (pfkA) was constructed and transferred into Acidithiobacillus
      thiooxidans Tt-Z2 by conjugation. The transfer frequency of plasmid from E. coli
      to Tt-Z2 was 2.6 x 10(-6). More than 68% of Tt-Z2 cells carried the recombinant
      plasmids after being cultured for 50 generations without selective pressure,
      which showed that pSDK-1 was maintained consistently in Tt-Z2. The pfkA gene from
      E. coli could be expressed in this obligately autotrophic bacterium but the
      enzyme activity (14 U/g was lower than that in E. coli (K-12: 86 U/g; DF1010
      carrying plasmid pSDK-1: 97 U/g). In th presence of glucose, the Tt-Z2
      transconjugant consumed glucose leading to a better growth yield.

PMID- 16281557
TI  - [Cloning and expression of a 2-naphthoate monooxygenase gene (nmo) in
      Burkholderia sp. JT1500].
AB  - A 4.8kb DNA fragment from one blue colony of the pLARF1 gene library of
      Burkholderia sp. JT1500 was subcloned to pUC18, designated as pEK123. The
      sequence of the inserted 4.8kb DNA' of pEK123 was analyzed and submitted to EMBL
      nucleotide database, the accession # is AJ566333. The transformants of pEK123
      could also become blue in LB agar and sequence analysis showed that three open
      reading frames and a putative promoter sequence were located in this inserted
      fragment. Then the 4.4kb insert fragment of pEK123 was double digested with Xba I
      / Kpn I and EcoR I / Xba I respectively to construct plamsids pXK3 and pEX12. The
      pXK3 contained only one 1158bp open reading frame (ORF) and pEX12 with other two
      ORFs. Unlike pEK123, the colonies of pEX12 did not show any blue color even
      incubated for 72h in LB agar, but the transformants of pXK3 did oxidize indole
      into indigo. The deduced 43kD protein of 1158bp ORF showed 64% homology of amino
      acid composition to Ralstonia eutropha HF39 hydroxylase (bec). Results of
      substrate transformation analysis showed that the transformants of pEK123 was
      able to catalyze the oxidation of 2-naphthoate but not other key intermediates in
      2-naphthoate metabolic pathway. These results confirmed that the product of
      1158bp ORF is 2-naphthoate monooxygenase. Though the oxygenase activity of pEK123
      is much higher than that of pXK3, SDS-PAGE analysis found no difference between
      the amount of the band of monooxygenase produced by pXK3 or pEK123, but one more
      band was found produced by pEK123. According to the difference of substrate
      analysis between pXK3 and pEK123, it is supposed that the products of two open
      reading frames up stream of nmo gene had strong influence on the activity of the
      monooxygenase. Benzoate was oxidized by free-cell extracts of the transformants
      of pEK123 in the transformation experiment with different aromatic substrates. As
      the DNA sequence and amino acid sequence of 2-naphthoate monoxygenase (nmo) did
      no show any homology with the DNA sequence and amino acid sequence of benzoate
      oxygenases reported, the pathway of benzoate oxidation conducted by nmo is on the
      investigation.

PMID- 16281558
TI  - [Cloning and expression of human canstatin and its purification and bioactivity].
AB  - Total RNA was extracted from placenta umbilical tissue and the canstatin cDNA was
      amplified from total RNA by net-RT-PCR technique. The amplified cDNA was cloned
      into pSP72 and sequenced. The canstatin cDNA was cut down from pSP72C with BamH I
      / Nde I and ligated into the vector pET-3c. The resultant plasmid pETC was then
      transformed into E. coli BL21 (DE3). The canstatin gene was efficiently expressed
      after IPTG induction as a 25 kD band on SDS-PAGE. The expressed product
      constituted approximately 27.9% of the total bacterial proteins estimated by
      densitometry and existed mainly as inclusion body. The inclusion bodies were
      washed, lysed, refolded and purified on the Sephadex G-75 gel filtration column
      to a purity of 91.4%. CAM assay showed that 10 microg purified canstatin is
      enough to inhibit the angiogenesis of chichen embryo microcapillary vessel.

PMID- 16281559
TI  - [Study on development of DNA microarrays for human papillomavirus (HPV)
      diagnosis].
AB  - To study the technology for establishing DNA microarrays for the diagnosis of
      HPV. HPV6, 11, 16 and 18 gene fragments were isolated and printed onto
      aminosilane-coated glass slides by PixSys 5500 microarray printer as probes to
      prepare the HPV. HPV samples, after labeled with Cy3 or Cy5, were hybridaized
      with the microarray followed by scanning for analysis. The experimental condition
      for preparing the HPV gene chips was investigated and the possibility of HPV
      genotying using DNA microarrays was discussed. The technique established in this
      study for preparing HPV DNA microarrays is applicable and has potential clinical
      application significance.

PMID- 16281560
TI  - [Differential expression of human macrophage genes encoding cytokines and their
      regulatory elements after Mycobacterium tuberculosis infection].
AB  - To investigate whether the genes encoding cytokines and their regulatory elements
      participated in the immune response to Mycobacterium tuberculosis infection.
      Expression microarray was employed to compare the avirulent strain and clinically
      isolated strains infection induced macrophage cytokine differential expression.
      Results were cytokines IFN, TNF, TGF, IL and their regulatory elements are
      involved in the immune reaction. IL-19 was first reported to be involved in the
      anti-Mtb immunity. Relative expression level of theses factors before and after
      infection were assayed too. The data provides clues for further scrutinize the
      role of cytokines and related elements in the interaction between Mycobacterium
      tuberculosis and host macrophage.

PMID- 16281561
TI  - [Detection and identification of Xanthomonas oryzae pv. oryzae and Xanthomonas
      oryzae pv. oryzicola by real-time fluorescent PCR].
AB  - A novel and sensitive real time PCR was developed to detection Xanthomonas oryzae
      pv. oryzae and Xanthomonas oryzae pv. oryzicola, which cause the bacteria leaf
      blight (BLB) and leaf streak respectively, Universal and specific TaqMan probes,
      which were designed based on the sequence of Putative siderophore receptor gene
      cds were used to detect 13 bacteria and one phytoplasmas, only in X. oryzae pv.
      oryzae and X. oryzae pv. oryzicola, fluorescent signal can be collected with
      their specific probes respectively. The level of detection of the probe was
      30.6fg plasmid, roughly equaling to one cell and 100 times sensitive than PCR gel
      electrophoresis detection. X. oryzae pv. oryzae and X. oryzae pv oryzicola were
      detected from seed washes and DNA extracted from the seed washes of naturally
      infected seeds and infected leaves as small as 10g naturally infected seeds or
      0.3g leaf. This method is little time consumption (only 2h) and without
      contamination from PCR product.

PMID- 16281562
TI  - [Studies on the properties of Cecropin-XJ expressed in yeast from Xinjiang
      silkworm].
AB  - The purpose of this study is to investigate the properties of recombinant
      Cecropin-XJ isolated from Xinjing silkworm and expressed in Pichia yeast.
      According to Agarose Diffusion Assay, this recombinant Cecropin-XJ has exhibited
      an extreme heat-stable characteristic and the ability to kill ampicillin
      resistant S. aureus and S. enterica. Moreover, we have observed that the Cecropin
      XJ well tolerant to extreme acidic, basic, and high salt environments as well as
      resistant to 24 hours digestion by artificial gastric juice. The inhibition
      capability to S. aureus with 1mg Cecropin-XJ is equal to 1200U ampicillin. With a
      broad spectrum of antibacterial activities, the Cecropin-XJ is able to inhibit
      the Gram-positive bacteria and Gram-negative bacteria. These findings could lead
      it to a broad applications for agriculture, medical, domestic animal and food
      industry. The further investigation of the antibacterial mechanism of cecropin-XJ
      is needed.

PMID- 16281563
TI  - [Analysis of the main amatoxins and phallotoxins in Amanita exitialis--a new
      species in China].
AB  - The content and distribution of the main Amatoxins (alpha-amanitin, beta
      amanitin) and Phallotoxins (Phallacidin, Phallisin, Phalloin, Phalloidin) in the
      three tissues (cap, stipe and volva) of Amanita exitialis were evaluated by means
      of high-performance liquid chromatography. The results showed that Amanita
      exitialis was a lethal mushrooms, the cap had the highest content of total
      toxins, it reached 8152.6 microg/g dry weight, the toxins content in stipe
      reached 3742.3 microg/g dry weight, whereas the volva had the lowest content of
      total toxins,it had only 1142.5 microg/g dry weight. The distribution of
      Amatoxins and Phallotoxins in the tissues were revealed and it displayed that the
      content of Amatoxins (alpha-amanitin and beta-amanitins especially alpha
      amanitin) in the cap, stipe or volva of A. exitialis was higher than that of
      Phallotoxins (Phallacidin, Phallisin, Phalloidin and Phalloin). But the content
      of Phallotoxins especially Phallacidin was gradationally higher from cap to stipe
      and to volva.

PMID- 16281564
TI  - [Purification and identification of surfactin isoforms produced by Bacillus
      subtilis B2 strain].
AB  - Crude lipopeptide was extracted with methanol from the pellet which was
      precipitated with 6 mol/L HCl from the culture medium of Bacillus subtilis B2
      strain. The crude lipopeptide was purified by gel filtration on Sephadex LH-20
      column, the obtained product was referred to as sub-pure lipopeptide. The MALDI
      TOF mass spectrum showed that B2 produced only lipopeptide surfactin. Sub-pure
      lipopeptide was run on muRPC C2/C18 column by HPLC SMART SYSTEM with aim at
      separation of surfactin isoforms. The surfactin isoforms fractions was detected
      by MALDI-TOF-PSD mass spectrometry, results indicated that the surfactin isoforms
      of B2 strain was cyclic lipodecapeptide L-Glu-L-Leu-D-Leu-L-Val-L-Asp-D-Leu-L-Leu
      containing fatty acid with a side chain length of 13, 14 and 15 carbon atoms.

PMID- 16281565
TI  - [Study on the degradation pathway of biphenyl by Rhodococcus pyridinovorans R04].
AB  - Metabolites of Rhodococcus pyridinovorans R04 from biphenyl were analyzed by GC
      MS. The results demonstrated that biphenyl was degraded via a route of 2,3
      dihydro-2,3-dihydroxybiphenyl and 2,3-dihydroxybiphenyl. 4-Benzoylbutyric acid
      and 1-phenylethanone were also found in the GC-MS analysis, which indicated there
      were other pathways beside the main route.

PMID- 16281567
TI  - [Detection of linear chromosomes and plasmids among 15 genera in the
      Actinomycetales].
AB  - Bacterial chromosomes and plasmids are commonly circular, however, linear
      chromosomes and plasmids were discovered among 5 genera of the Actinomycetales.
      Here, we use pulsed field gel electrophoresis to study the genomes of 19 species
      which belong to 15 genera in the Actinomycetales. All chromosomes of 19 species
      are linear DNA, and linear plasmids with different sizes and copy numbers are
      detected among 5 species. This work provide basis for investigating the possible
      novel functions of linear replicons beyond Streptomyces and also helps to develop
      Actinomycetales artificial linear chromosome.

PMID- 16281566
TI  - [Breeding of excellent baker's yeast strain with good flocculation].
AB  - An excellent baker's yeast strain ZLTH-58 (MATa/alpha, leu-, FLO1) with high
      biomass, high-sugar-tolerance and good flocculation was constructed by primary
      screening, isolation of haploid, mutagenesis, cloning and expression of FLO1 gene
      and hybridization. The results showed that strain ZLTH-58 had excellent
      properties of the parental strains BL56 and BL61. The biomass of strain ZLTH-58
      was 1.21 times of the parental strain BL56; The ability of high-sugar-tolerance
      of strain ZLTH-58 was higher than the parental strain BL61. The ability of
      flocculation of strain ZLTH-58 was better than the parental strains BL56 and
      BL61. The factors that affected the biomass of strain ZLTH-58 were also detected.
      Biomass reached 83.06 g/L under the optimal fermentation conditions, having a
      1.35-fold improvement. Strain ZLTH-58 is also stable in genetics characters by
      analysis of genetic stability and it has the potential for use in industrial
      processes.

PMID- 16281568
TI  - [Novel functions of the Actinomycetales linear replicons and its applications].

PMID- 16281570
TI  - [Progress on molecular mechanism of Staphylococcus epidermidis biofilm].

PMID- 16281569
TI  - [Research progress on the squalene synthase].

PMID- 16281572
TI  - Traditional wellness initiatives delve deeper into DM waters.
AB  - Wellness initiatives delve deeper into DM. DM-style interventions are finding a
      place at the worksite as employer-payers look for new ways to trim costs, boost
      productivity, and prevent low-risk employees from moving into higher risk
      categories. See how wellness programs are expanding to meet the needs of the
      chronically ill at work.

PMID- 16281571
TI  - New HF guidelines emphasize prevention, end-of-life decisions.

PMID- 16281573
TI  - Taking the middle ground in the build vs. buy dilemma.
AB  - A third solution in the build vs. buy dilemma. Deciding whether to outsource for
      DM services or build a program internally can be a tough call--especially for
      smaller plans. However, Blue Cross of Idaho opted for a third course of action
      that provides the plan with the decision support it needs without giving up local
      control. See how the approach works to the health plan's advantage.

PMID- 16281574
TI  - Leveraging the power of EMRs to drive DM.
AB  - The future is now for EMR-driven DM. While most health care organizations have
      yet to enjoy the operational efficiency that system-wide EMRs can offer, a few
      pioneering groups are already reaping the clinical rewards that can be achieved
      through EMR-driven DM initiatives. In fact, Portland, OR-based Providence Health
      System has had enough success with its CareManager system that it has partnered
      with Kryptiq Corporation to offer the DM program to other groups--even while it
      continues to develop the application.

PMID- 16281575
TI  - [The JDDG on its own account].

PMID- 16281576
TI  - [Lichen sclerosus and squamous cell carcinoma of the vulva].
AB  - Genital lichen sclerosus in women is a clinically and histologically well defined
      disease. In addition to the classical atrophic form, there is a hypertrophic
      variant, which is characterised histologically by squamous cell hyperplasia. The
      aetiology is unknown but an autoimmune pathogenesis seems most likely. Infectious
      or hormonal influences do not play a major role. We describe a squamous cell
      carcinoma of the vulva with a co-existing lichen sclerosus. This case raises
      again the question of a precancerous potential of lichen sclerosus. In the
      dermatological literature, only a few cases with association of lichen sclerosus
      and squamous cell carcinoma are known. This is in contrast to gynaecological
      literature, where a high number of squamous cell carcinomas has been described.
      Gynaecologists search for the histological findings of lichen sclerosus adjacent
      to squamous cell carcinoma. Such an attempt is not valid without the clinical
      signs of lichen sclerosus, so that indeed classical lichen sclerosus does not
      seem to be a precancerous lesion. On the other hand, the hypertrophic form of
      lichen sclerosus seems to be associated with squamous cell carcinoma in about 3
      5% of case.

PMID- 16281577
TI  - [Micrographic controlled surgery (3D-histology) in cutaneous melanoma].
AB  - Frederic E. Mohs was the first to apply micrographic surgery in cutaneous
      surgery. As a result in the English literature, micrographic surgery (3D
      histology) is usually called Mohs micrographic surgery (MMS). Techniques of 3D
      histology have been applied in various skin tumours. The method is most suitable
      for tumours with continuous spread. Excisions with 3D-histology can be performed
      with smaller initial safety margins. Thus less normal tissue is excised and often
      better cosmetic results can be obtained. Techniques of 3D-histology such as the
      Mohs technique (MMS) and the "Tuebingen Cake" technique are compared with routine
      histopathology. In addition, the current status of 3D-histology in cutaneous
      melanoma is assessed. Prospective randomized studies on 3D-histology in cutaneous
      melanoma are not available. Nevertheless, 3D-histology should usually be employed
      for lentigo maligna melanoma. In functionally and cosmetically important areas
      (face, hand, foot) 3D-histology may allow reduced safety margins in other
      histological types of cutaneous melanoma.

PMID- 16281578
TI  - [Efficacy, side effects and patient satisfaction with wrist conduction block
      anaesthesia prior to the treatment of palmar hyperhidrosis with botulinum toxin
      type A].
AB  - BACKGROUND: The treatment of palmar hyperhidrosis with botulinum toxin type A
      (BTX A) injections is one of the most effective therapeutic options. However,
      without adequate anaesthesia this treatment is not feasible in most patients. The
      anaesthesia of the radial, median and ulnar nerves (wrist block) is despite the
      absence of good data considered effective but risky. PATIENTS AND METHODS:
      Between 1.10.1999 and 30.9.2001 retrospectively the efficacy, side effects and
      the patient satisfaction regarding the overall performance of the wrist block
      prior to the treatment of the palmar hyperhidrosis with BTX A was investigated.
      The study took place at the department of dermatology in Mannheim. RESULTS: Of
      the 38 patients treated, 33 were finally included into the trial. The patients
      chose the average score of 7,9 +/- 2,1 (sd) on a scale from "0" to "10" (not at
      all effective--maximally effective) for the efficacy of the wrist block in
      reducing pain. The patients were very content with the wrist block and granted it
      the average score of 7,7 +/- 2,1 (sd) on a scale from "0" to "10" (not at all
      content--maximum content). Unwanted effects could be seen in 31/33 patients
      (93,9%): these were dizziness, headache or haematoma at the spot of injection as
      well as pain caused by the injections of the local anaesthesia or paresthesias
      such as tickling of the hand or arm. All side effects caused by the wrist block
      were reversible and lasted--except in one patient--only for a short time. 29/33
      patients (87,9%) recommended the wrist block prior to treating palmar
      hyperhidrosis with BTX A and 28/33 patients (84,9%) could not imagine to agree to
      such a treatment without local anaesthesia. CONCLUSION: The wrist block
      effectively reduces pain due to the treatment of palmar hyperhidrosis with BTX A.
      Major side effects are rare; patient acceptance and satisfaction are high.

PMID- 16281579
TI  - Effect of the vehicle on the amount of stratum corneum removed by tape stripping.
AB  - BACKGROUND: The penetration of topically applied substances into the stratum
      corneum can non-invasively be studied using the tape stripping procedure. This
      method was applied to investigate in vivo the penetration of a fragrance,
      vanillin, applied in ethanol and a w/o emulsion. METHODS: Twenty tape strips were
      removed from each skin area treated with vanillin in ethanol or w/o emulsion,
      respectively. The concentration of vanillin was determined for each tape strip.
      In addition, the pseudo-absorption of the corneocytes was determined to calculate
      the SC profile. RESULTS: The vanillin concentration was correlated both with the
      tape number and with the stratum corneum profile. Depending on whether the tape
      number or the profile of the stratum corneum were correlated with the vanillin
      concentration, different distributions within the stratum corneum were obtained.
      Different amounts of stratum corneum were removed with 20 tape strips dependent
      on the vehicle applied previously. The application of the w/o emulsion led to the
      removal of nearly the half the amount of corneocytes stripped from the ethanol
      treated area. CONCLUSIONS: The results obtained underline the general necessity
      to correlate the amount of stratum corneum with the amount of substance in
      penetration studies.

PMID- 16281580
TI  - [Diagnostic pitfall: herpes simplex recidivans on the finger].
AB  - Herpes simplex recidivans is one of the most common dermatological infections. In
      typical (perioral, labial or genital) localization, the diagnosis is simple and
      often made by the patient. In atypical locations, the disease may be misdiagnosed
      by the physician. A 28-year-old patient presented with recurrent herpes simplex
      virus exacerbations on his left index finger, accompanied by neuralgic pains and
      lymphadenitis. He had been misdiagnosed by a variety of specialists for several
      years and had often been unable to work. The diagnosis of recurrent herpes
      simplex was made by the patient's history and the clinical symptoms and was
      confirmed by the detection of Herpes simplex virus-specific DNA by PCR.

PMID- 16281581
TI  - [Nitric oxide in the pathogenesis of inflammatory dermatoses].

PMID- 16281582
TI  - [Persistent papule/mole blisters/pustules papulary pustels on the face of a 21
      year old man].

PMID- 16281583
TI  - [Cosmetic dermatology in German dermatology departments--outcome of a national
      survey].
AB  - The demand for non-surgical cosmetic treatments has grown considerably in recent
      years. It appears German dermatology departments now also increasingly seem to
      offer many of these methods. In 2001 we evaluated the use of different non
      surgical cosmetic techniques in German dermatology departments through means of a
      national questionnaire. Information was requested from 85 departments, of which
      63.5% responded. The outcome revealed that 96.3% of the participating departments
      have lasers at their disposal to treat cosmetic skin lesions, 79.6% carry out
      injections with botulinum toxin, 59.3% perform chemical peels and 37% perform
      tissue augmentation with injectable fillers. Overall, the ratio between desired
      and adverse effects as well as the economic benefit of all evaluated methods was
      judged as positive by the interviewees. In a comparison of all evaluated
      modalities, the therapeutic index was considered most favourable with botulinum
      toxin and most unfavourable with injectable filling agents. With regard to cost
      effectiveness, soft tissue augmentation was judged best, while chemical peels
      alongside lasers were regarded as least advantageous in this respect. Further
      evaluated topics were indications, substances, organisation and other issues. In
      summary the survey confirmed that a large number of German dermatology
      departments employ non-surgical cosmetic procedures matching the international
      upward trend of cosmetic dermatology.

PMID- 16281584
TI  - [Imiquimod--a substance with a broad working spectrum].

PMID- 16281585
TI  - [Thromboangiitis obliterans: an overview].
AB  - Thromboangiitis obliterans is a vascular disease characterized by a segmental,
      non-atherosclerotic inflammation of the small and medium-sized arteries and
      veins. The vascular changes are mainly found on the distal extremities.
      Involvement of visceral organs is rare. Affected patients are mostly young male
      smokers, who develop ulcers and gangrene of the toes and fingers as a result of
      the vascular ischaemia. Diagnosis is made using characteristic clinical criteria
      as well as pathological findings in arteriography and histopathology. Although
      the exact underlying causes of Buerger's disease are still unknown, the disease
      is strongly associated with tobacco smoking. Although most investigators
      speculate about an autoimmune mechanism, no causative antigens have yet been
      discovered. The only definite form of therapy is the discontinuation of tobacco
      use. On the basis of smoking cessation, further therapies (e.g. administration of
      prostacyclin analoga) are possible. The mortality rate for patients with
      Buerger's disease is not higher than that for the rest of the adult population,
      but patients often require minor and major limb amputation due to ulcerations.

PMID- 16281586
TI  - [Syphilis with HIV coinfection].
AB  - In recent years a rising incidence of syphilis has been observed, especially in
      the population of homosexual men. Because of altered sexual behavior in terms of
      increased promiscuity paralleled by decreased use of condoms and the fact that a
      syphilis infection increases the susceptibility to HIV coinfection, the incidence
      of HIV is also rising once again in this population. In patients with HIV
      coinfection, the course of syphilis is often atypical or dramatic. Stage-specific
      features suggesting coinfection include prolonged primary ulcers persisting well
      into the secondary stage, numerous atypical cutaneous findings in the second
      stage and a rapid progression from stage to stage. The diagnosis of syphilis may
      be more difficult because of false positive or false negative serological
      findings in patients with HIV coinfection. Whether or not the CNS is more often
      involved is this patient group has not been established by prospective studies
      and remains controversial. However, WHO and CDC recommendations include
      evaluation of the CSF in HIV-infected patients with either late syphilis or when
      the time course is unknown period. There is worldwide agreement on the therapy of
      syphilis in patients with HIV coinfection. Patients with early syphilis should be
      treated with 2.4 benzathine penicillin i.m. once or twice; patients with late
      syphilis, twice or three times. Patients presenting with clinical or serological
      signs of neurosyphilis require 18-24 million IU penicillin i.v. daily for at
      least 2 weeks.

PMID- 16281587
TI  - [Azelaic acid 15% gel in the treatment of acne vulgaris. Combined results of two
      double-blind clinical comparative studies].
AB  - BACKGROUND: Topical measures are still the mainstay in the therapy of mild-to
      moderate acne vulgaris. Azelaic acid 20% in a cream formulation has been
      established as an efficacious and safe topical drug for 15 years. A new non
      alcoholic hydrogel formulation containing 15% azelaic acid was clinically tested
      against two standard drugs--5% benzoyl peroxide (BPO) and 1% clindamycin.
      PATIENTS AND METHODS: In two independent, randomized, blinded comparative trials
      15% azelaic acid gel was clinically tested against 5% benzoyl peroxide (BPO) gel
      in 351 patients and against 1% clindamycin gel in 229 patients. The drugs were
      applied b.i.d. for 4 months. RESULTS: Azelaic acid 15% gel proved to be as
      effective as BPO and clindamycin with median % reduction of the inflamed lesion
      (papules and pustules) of 70%, and 71% respectively. The azelaic acid gel was
      well-tolerated, the side effects (local burning and irritation) were distinctly
      less than with BPO but more pronounced than with clindamycin. Despite these side
      effects, the treatment was well-accepted by the majority of patients.
      CONCLUSIONS: Azelaic acid gel is an effective topical monotherapy for mild-to
      moderate acne vulgaris; its new gel form is an enrichment of acne therapy.

PMID- 16281588
TI  - [Imiquimod for the topical treatment of focal epithelial hyperplasia (Heck
      disease) in a child].
AB  - Focal epithelial hyperplasia (FEH) or Heck disease is a rare skin disease caused
      by human papilloma viruses (HPV). The case of a 9-year old boy is presented to
      demonstrate the successful treatment of massive FEH with 5% imiquimod cream.
      Initially, the patient had noticed several separate papules, which spread and
      developed into multiple peri- and intraoral papillomatous nodules. The lesions
      were treated with carbon dioxide laser destruction. However, multiple, skin
      coloured papillomatous nodules were found on the tongue, buccal mucosa and lips
      1.5 years later. Treatment with imiquimod was initiated, because the patient
      suffered tremendously from the disease. 5% imiquimod cream was applied 3 times
      per week. Regression of lesions was obvious after 1 month of treatment. Complete
      clearance was achieved after 2 additional months of treatment and no recurrence
      was detected over a follow-up period of 5 months. Our case points out the
      clinical value of imiquimod for the non-traumatic and almost painless therapy of
      HPV-induced skin diseases in children.

PMID- 16281589
TI  - [Pemphigoid gestationis--first sign of metastatic choriocarcinoma].
AB  - A 29-year-old woman developed pruritic urticarial plaques and vesicles 3 months
      after delivery of a healthy daughter. Two months later pemphigoid gestationis
      (PG) was diagnosed based on histopathological and immunopathological findings. At
      the same time elevated serum levels for beta-HCG and a large mass in the liver
      were noted. A liver biopsy confirmed the diagnosis of metastatic choriocarcinoma,
      which was responsible for the PG metastasis. Upon initiation of chemotherapy,
      complete healing of the PG was observed within 4 weeks and autoantibodies to
      BP180NC16A could no longer be identified. In parallel, both a decrease of beta
      HCG levels and tumor size was observed.

PMID- 16281590
TI  - [Chronic favus caused by infection with Trichophyton schonleinii].
AB  - A 25-year-old female patient from Kosovo presented with a slowly progressive
      cicatricial alopecia which had started when she was 6 years old. Her brother in
      Kosovo had similar lesions. At the erythematous border of the hairless area,
      crusts, erosions and pustules were apparent. Mycological examination identified
      Trichophyton schonleinii, the causative pathogen of favus. Histological
      examination revealed hyphae and showed no features suggestive of other causes of
      cicatricial alopecia. Systemic terbinafine combined with topical
      ciclopiroxolamine resulted in rapid improvement of this disease which is seldom
      seen in Central Europe.

PMID- 16281591
TI  - [Prevention of atopic eczema].

PMID- 16281592
TI  - [Tender livid papules].

PMID- 16281593
TI  - [Erythematous, acrally prominent plaques in a 66 year old woman].

PMID- 16281594
TI  - [Oral candidiasis].

PMID- 16281595
TI  - [Multiple erythematous plaques with steady progression].

PMID- 16281596
TI  - 4th Intercontinental Meeting of Hair Research Societies 2004 the "World of Hair".

PMID- 16281597
TI  - Differential diagnosis of hair loss in children.
AB  - Hair loss in childhood covers a broad differential diagnosis and often presents
      the involved dermatologist and pediatrician with a diagnostic and therapeutic
      challenge. Correct classification of the hair disease, especially in the case of
      underlying genetic syndromes, metabolic defects or endocrine disorders, is often
      an important prerequisite for continued normal physical and mental development of
      the young patients. Dealing with hair loss in childhood, one should differentiate
      between congenital and acquired diseases. The clinical manifestation profile, the
      age of the patient when the initial manifestation occurred, and the presence of
      associated symptoms are important for the classification of the hair disease. In
      the present paper, a classification of hair loss in childhood based on clinical
      appearance, age of onset and associated symptoms is proposed as a guide for the
      evaluation of hair loss and alopecia in childhood.

PMID- 16281598
TI  - Estrogens and the hair follicle.
AB  - While it is undisputed that estrogens (1 beta-estradiol, E2) are mainly involved
      in skin physiology and operate as potent hair growth modulators, our knowledge
      about the estrogen target cells in skin and exact signaling pathways is still
      very limited. The current review provides an overview of estrogen effects on hair
      follicle cycling, cutaneous expression of estrogen receptors, and potential
      functions of estrogens in hair biology. We discuss potential target genes of
      estrogen receptor-mediated signaling in the skin, explore the interplay of
      estrogens with other hormones, growth factors and enzymes, and define major open
      questions in this intriguing and far too long neglected area of hair research.

PMID- 16281599
TI  - [Tertiary prevention of occupational skin diseases].
AB  - BACKGROUND: Inpatient tertiary prevention of occupational skin diseases is
      indicated when the employee is threatened with loosing their job. Earlier studies
      have shown that with intensive tertiary preventive measures, 2/3 of such
      individuals can continue their jobs long-term. Data on the effectiveness of
      tertiary prevention for various occupational groups has not been previously
      available. PATIENTS AND METHODS: The outcome of all participants treated in the
      year 2002 was analyzed according to occupational groups with respect to
      diagnosis, medical intervention prior and during the inpatient period. RESULTS:
      In 91% of 296 cases contact dermatitis of the hands was diagnosed (75% primary
      irritant contact dermatitis (37% chronic irritant contact dermatitis, 38%
      irritated atopic hand eczema, 16% allergic contact dermatitis). Clinically
      relevant Type IV-delayed hypersensitivity (allergic contact dermatitis) reactions
      were identified in 42% of cases; in most cases, the delayed hypersensitivity
      followed irritant contact dermatitis. In more than 83% of cases, a complete or
      nearly complete remission was achieved. Clinical relevant Type IV sensitization
      was most frequent in hairdressers (66%). Cleaning and housekeeping personnel most
      frequently used corticosteroids on a regular basis (60%) and most often
      experienced corticosteroid withdrawal (53%) and atrophy of the skin of the hands
      (23%). CONCLUSION: The data from studies on the tertiary prevention of
      occupational skin diseases reveal strategies for the optimization of outpatient
      care indicate specific occupational risk factors. The variance between
      professions may reflect differing approaches to secondary prevention.

PMID- 16281600
TI  - [Standards and perspectives of dermatology in Germany].

PMID- 16281601
TI  - Unusual association between acrokeratosis verruciformis of Hopf and multiple
      keratoacanthomas. Successful therapy with acitretin.
AB  - A 62-year-old man presented with the unusual association of acrokeratosis
      verruciformis of Hopf and multiple keratoacanthomas. Both conditions were treated
      successfully with acitretin.

PMID- 16281602
TI  - [Papuloerythroderma of Ofuji with urticarial lesions].
AB  - Papuloerythroderma of Ofuji is a rare disease that mainly affects older men of
      Asiatic origin. Clinically, it is marked by highly pruritic papules which form
      larger plaques or may give rise to erythroderma. Larger body folds of the abdomen
      are typically spared (deckchair sign). There is a dispute whether
      papuloerythroderma of Ofuji represents an own entity or should be regarded as a
      variant of other inflammatory, neoplastic, or paraneoplastic dermatoses. We
      present a case of papuloerythroderma of Ofuji in a European patient in which the
      clinical course as well as the laboratory and histology suggested a relation to
      mycosis fungoides. Our patient developed pruritic urticarial plaques when
      systemic corticosteroids were tapered, but cleared complete with cyclosporin A.

PMID- 16281603
TI  - [New aspects in the pathogenesis of psoriasis].

PMID- 16281604
TI  - [Eruptive spread of erosive skin lesions in a 33-year old patient].

PMID- 16281605
TI  - [Tinea capitis].

PMID- 16281606
TI  - [H. J. Schwanitz: a life for occupational dermatology].

PMID- 16281607
TI  - [Prevention and regeneration of barrier disturbances in occupational
      dermatology].
AB  - Over the past 10 years primary, secondary and tertiary prevention of occupational
      skin disorders has been shown to be successful, documented with appropriate
      statistical methods. Interventional strategies are the main features of secondary
      and tertiary prevention, now well-established in occupational dermatology.
      Primary prevention is best accomplished by health education measures, both in the
      form on individual counseling and seminars. This overview reviews the scientific
      background of hand eczema with respect to barrier damage and repair and then
      considers the options for individualized and focused prevention. Special
      anatomical features of the interdigital space and palms, as well as functional
      disorders, such as palmar hyperhidrosis, are discussed. The importance of barrier
      regeneration is considered in light of the role of an acid pH, the epidermal
      calcium gradient and aspects of percutaneous absorption. The effects of anti
      oxidants are considered, and new bioengineering methods which rely on physiologic
      measuring techniques are reviewed.

PMID- 16281608
TI  - Keloids--clinical diagnosis, pathogenesis, and treatment options.
AB  - Keloids are defined as excessive scar tissue formation extending beyond the area
      of the original skin injury and occurring in predisposed individuals. They are
      considered to be a result of abnormal wound healing. The pathogenetic mechanisms
      that cause keloids remain unknown. Experiments with cells derived from keloid
      tissue revealed a number of abnormalities in cellular functions, such as in
      proliferation, apoptosis, or expression of growth factors and extracellular
      matrix proteins. Furthermore, several studies have reported altered keratinocyte
      fibroblast interactions in keloids. Despite the diverse pathological changes in
      cellular functions and expression profiles of cells derived from keloid tissue,
      recent genetic studies have provided evidence that single genes may act as major
      regulators of keloid formation. We provide an overview of the pathogenetic
      mechanisms of keloid formation in the context of their clinical characteristics
      and current therapeutic approaches.

PMID- 16281609
TI  - Determination of the formation of the stratum corneum reservoir for two different
      corticosteroid formulations using tape stripping combined with UV/VIS
      spectroscopy.
AB  - BACKGROUND: The stratum corneum, the outermost layer of the skin, not only
      represents a barrier, but also a reservoir for topically applied substances. Both
      properties influence the penetration process, as does the vehicle. It determines
      the penetration pathway and the retention time of the topically applied
      substances. METHODS: Two commercial products (Temovate Cream and Temovate
      Emollient), both containing 0.05% clobetasol propionate, were applied on the
      inner forearms of healthy volunteers. 20 tape strips were removed from each
      treated skin area. The horny layer profile was determined measuring the
      absorption of the corneocytes at 430 nm. The concentration of clobetasol
      propionate on the individual tapes was then analyzed. RESULTS: We found
      differences in the reservoir formation depending on the formulation applied,
      which correlated to the biological response in the form of a blanching effect.
      CONCLUSIONS: The method applied is well-suited to determine the reservoir
      formation in the stratum corneum for topically applied substances.

PMID- 16281610
TI  - [Dermatology at the University Hospital of Mbarara, Uganda].
AB  - The Georg Klingmuller Clinic is part of Mbarara University Teaching Hospital
      (MUST) in south-western Uganda. Established in 1999, this clinic cares for about
      6,000 dermatological patients per year. We review the disease spectrum, available
      diagnostic tools, and therapeutic options in this clinic. In addition, the
      importance of dermatology for the fight against HIV/AIDS is discussed with
      respect to the socio-economic background of a sub-Saharan country. Co-operation
      with dermatology departments in Germany may not only help to diagnose skin
      diseases in Mbarara, but may also be valuable for the visiting dermatologist to
      manage the increasing numbers of patients with dark skin at home.

PMID- 16281611
TI  - [Anaphylaxis after injection of corticosteroid preparations-
      carboxymethylcellulose as a hidden allergen].
AB  - Two patients developed anaphylaxis after injection of a corticosteroid
      preparation containing carboxymethylcellulose (E466). In both cases skin tests
      yielded positive immediate type reactions to pure carboxymethylcellulose. This
      hydrophilic derivative of cellulose has found wide application in the
      pharmaceutical, cosmetics and food industry. The diagnosis is based on skin
      testing as 9% of the normal population was found to have serum IgE antibodies to
      this compound. In case of anaphylaxis after injection of corticosteroids,
      carboxymethylcellulose in addition to corticosteroids should be included for skin
      testing.

PMID- 16281612
TI  - [Zosteriform pigmented purpura of Schamberg: case report and differential
      diagnosis of zosteriform skin lesions].
AB  - A 13-year-old boy presented with progressive pigmented purpura of Schamberg in an
      unusual zosteriform distribution. He recently has taken methylphenidate which has
      not been described as a cause of Schamberg disease. Many different skin diseases
      can present in a zosteriform distribution. They are reviewed systematically and
      sorted by pathogenetic criteria.

PMID- 16281613
TI  - [Systemic ALlambda amyloidosis associated with vascular fragility].
AB  - A 63-year-old patient had experienced bilateral spontaneous periorbital
      hemorrhage for one year. After hospitalization because of recurring hemoptysis,
      biopsies of skin and colon revealed systemic ALlambda amyloidosis. In addition,
      the heart and lungs appeared to be involved. Monoclonal gammopathy was excluded
      by a normal plasma cell count and a polyclonal expression pattern in a bone
      marrow sample and by radiographic examination. The patient was treated with a
      relatively non-aggressive regimen of melphalan and prednisolone monthly with
      careful hematologic monitoring. This approach led to a significant improvement in
      relevant parameters. Recent advances in diagnosis, monitoring and therapy have
      made it easier to manage patients with amyloidosis with their poor prognosis.

PMID- 16281614
TI  - [Histopathology of photodermatoses].

PMID- 16281615
TI  - [Follicular papules and plaques with effluvium].

PMID- 16281616
TI  - [Recommendations for standards of water iontophoresis].

PMID- 16281617
TI  - [Carl Adolph von Basedow on the on the occasion of the 150th anniversary of the
      day he died].
AB  - In 2004 we commemorate the 150th day of death of Carl Adolph von Basedow, who
      takes a lasting place in the history of medicine for his description of the
      Merseburg triad (exophthalmos, goitre, tachycardia) with hyperthyroidism. There
      has been a long-lasting dispute over who first described these diagnostic
      features. In Germany, the dermatologically-relevant features of hyperthyroidism
      are known as Basedow disease. In the Anglo-American literature the name "Graves'
      disease" is predominately used, but also authors such as Parry or Flajani are
      also recognised. More than 60 other publications concerning arsenic poisoning,
      gonorrhoeal arthritis, anthrax, thrombophlebitis as well as a variety of surgical
      and gynaecological problems reflect the vast field of activity and broad
      scientific interests of the family doctor Basedow, who reached brilliant and
      lasting achievements on his own and without considerable resources.

PMID- 16281618
TI  - [Integrated health care--new opportunities for the specialist].

PMID- 16281619
TI  - [Pustular diseases of the newborn].
AB  - In the newborn, there exists a wide spectrum of pustular skin diseases. These
      range from transitory, benign adaptation disorders up to systemic, life
      threatening illnesses. In 30-60% of newborns pustules are observed in association
      with the relatively harmless Erythema toxicum, the origin of which is still
      unknown today. It is necessary to differentiate this from the pustular diseases
      which may be of infectious or non-infectious nature and which require therapy.
      Typical pathogens include Malassezia furfur, Staphylococci, Streptococci, Candida
      spp. and the herpes virus group.

PMID- 16281620
TI  - [Alpha-glucosylrutin, a highly effective flavonoid for protection against
      oxidative stress].
AB  - The flavonoid alpha-glucosylrutin (AGR) is a potent antioxidant with a high
      epidermal bioavailability. This makes this substance particularly suitable for
      various dermato-cosmetic applications. Flavonoids are phytamines with a common
      chemical structure and a broad range of activities, the most prominent being
      their radical scavenging ability. Reactive oxygen species (ROS) damage cells by
      different mechanisms. Direct cytotoxic effects include destruction of the cell
      membrane by causing radical chain reactions or induction of mutagenic changes in
      the nuclear and mitochondrial DNA. Indirect changes involve modification of
      intracellular signal transduction pathways that regulate inflammatory or
      proliferative activities. The excellent antioxidant efficacy of AGR has been
      shown in various experimental studies, both in vitro and in vivo. Subsequent
      clinical studies have demonstrated that AGR is also effective in the prevention
      of dermatologic diseases in which oxidative stress is of pathogenetic relevance,
      e.g. in polymorphous light eruption (PLE). Other promising dermato-cosmetic areas
      for AGR application are aging of the skin, especially photoaging. All in vivo
      evaluations indicate that AGR in the applied concentrations is a very well
      tolerated ingredient for medical skin care preparations.

PMID- 16281621
TI  - [Longitudinal melanonychia induced by hydroxyurea therapy].
AB  - Four case reports of patients with myeloproliferative syndrome receiving therapy
      with hydroxycarbamide (synonymous: hydroxyurea) and developing streaky
      longitudinal pigmentation appeared in fingernails and toenails several months
      after starting this therapy. BACKGROUND: Pigmentation of finger- and toenails
      presents a wide range of differential diagnostic considerations. They can be of
      infectious, melanocytic or exogenous origin or caused by metabolic disorders.
      PATIENTS AND METHODS: Three women and one man, ranging in age from 62 and 87
      years, were treated with hydroxycarbamide for myeloproliferative syndrome or
      chronic myelogenous leukemia for five to twelve years. All four patients were
      Fitzpatrick skin types II. RESULTS: Several months after starting this therapy,
      they developed streaky longitudinal pigmentation of their fingernails and
      toenails. In two patients, these findings were diagnosed by chance, whereas two
      patients sought dermatological advice because of nail pigmentation. In two of the
      patients the longitudinal pigmentation disappeared a few month after
      discontinuation of hydroxycarbamide. The melanonychia persisted in another
      patient, while the fourth was lost to follow-up. CONCLUSIONS: When melanonychia
      is identified in hematology-oncology patients, a careful medical history should
      be obtained. A list of medications is crucial, since hydroxycarbamide causes nail
      pigmentation. In each case of nail pigmentation, an acral lentiginous melanoma
      must be excluded.

PMID- 16281622
TI  - How to get your paper accepted in an English-language journal.

PMID- 16281623
TI  - [The "red melanoma"--a rare form of amelanotic malignant melanoma].
AB  - The two major variants of amelanotic malignant melanoma are the verrucous and the
      polypoid forms. A further--albeit rare--red eczematous variety has also been
      described. We report two female patients with reddish, non-pigmented, scaly
      lesions on the upper arm and the shoulder that had developed 2 to 3 years
      previously. One biopsy showed the diagnosis of a melanoma growing in situ while
      the second revealed a highly atypical melanocytic tumour. However, the
      histopathological examination of the entire tumour showed a superficial spreading
      amelanotic malignant melanoma. Therefore, in non-healing erythematous lesions,
      even without pigmentation or ulceration, the rare differential diagnosis of
      amelanotic malignant melanoma should be taken in consideration and a biopsy
      should be performed prior to therapy without histological control.

PMID- 16281624
TI  - [Pseudosarcomatous variant of a genital fibroepithelial stromal polyp in a
      pregnancy].
AB  - Fibroepithelial stromal polyps are benign neoplasms of the lower genital tract
      occurring mostly in young to middle-aged women in their reproductive years.
      Clinically they appear as tender, skin-colored, sack-like tumors and usually have
      a bland microscopic appearance. Sometimes, especially during pregnancy or with
      hormone therapy, a worrisome hypercellular and pseudosarcomatous pattern can be
      seen in the dermis. Awareness of this neoplasm with a possibly high degree of
      atypia is of crucial importance in order to avoid unnecessary radical surgery.

PMID- 16281625
TI  - [Miliaria and follicular atrophodermia as an early sign of Bazex-Dupre-Christol
      syndrome].
AB  - The Bazex-Dupre-Christol syndrome (BDC syndrome) is a rare X-chromosomal
      dominantly inherited genodermatosis. Major symptoms are (1) follicular
      atrophoderma, (2) congenital hypotrichosis, and (3) multiple basal cell
      carcinomas, the latter appearing in the second or third decade. More variably
      associated findings are milia, hypohidrosis, disorders of cornification,
      hyperflexibility of joints, and skeletal abnormalities. A 2.5-year-old Turkish
      girl presented with early signs of BDC syndrome in the form of milia, follicular
      atrophoderma on the face and hands, and hypotrichosis. Accurate diagnosis of this
      genodermatosis is necessary to prevent the development of basal cell carcinomas
      by sun protection and regular dermatological inspection.

PMID- 16281626
TI  - [Primary cutaneous B-cell lymphomas].

PMID- 16281627
TI  - [Nodular erythema and B-symptoms].

PMID- 16281628
TI  - [A beardless 34-year-old male patient].

PMID- 16281629
TI  - [Topical skin therapy with glucocorticoids--therapeutic index].

PMID- 16281630
TI  - [10 years "Doctors in Aid of Children with Skin Diseases in Africa"--personal
      impressions].
AB  - Within the scientific establishment of dermatology, it is difficult to initiate
      or to support basic dermatology services in Third World countries. The author
      describes his experiences over 10 years in backing a community-based health care
      project in western Kenya. The problems with supporting tropical dermatology in
      Germany are also discussed.

PMID- 16281631
TI  - [Remarks on the opinions of the DSTDG on the current situation of syphilis
      therapy in Germany. JDDG 2003; 1:668].

PMID- 16281632
TI  - [Wart treatment, evidence-based].

PMID- 16281633
TI  - [Body piercing--risks, consequences and psychological background of a cultural
      phenomenon].
AB  - Many different medical specialists are confronted with the increasingly popular
      practice of body piercing in their daily practice. This paper describes the most
      typical forms of this body modification practice, their origins and peculiarities
      as well as their complications and side effects. Some of the multi-facetted and
      often intense psychological motivations for body piercing are explored.

PMID- 16281634
TI  - [Lipoedema--current status, new perspectives].
AB  - Because of the lifelong and often progressive course and the mental trauma to the
      patients, lipoedema is an important dermatologic disorder. Complex physical
      therapy programs were introduced as a standard therapy years ago and can achieve
      an impressive oedema reduction. Liposuction in tumescent local anesthesia with
      vibrating microcannulas has proved to be a new effective treatment. A targeted
      and permanent reduction of the fat tissue leads to an increased quality of life
      due to an improved appearance, reduced tendency to swelling and less pain.

PMID- 16281635
TI  - [Efficacy and benefit of a 5-FU/salicylic acid preparation in the therapy of
      common and plantar warts--systematic literature review and meta-analysis].
AB  - BACKGROUND: (1) Salicylic acid (SA) and 5-Fluorouracil (5-FU) are effective drugs
      in wart therapy. (2) In Germany, increasing data on the benefit and the economic
      efficiency of drugs at Level I of evidence-based medicine are needed. METHODS:
      Evaluation of the effectiveness and benefits of a drug combination containing 0.5
      % 5-FU and 10% SA in the therapy of (a) common and (b) plantar warts in form of a
      two-step procedure--(1) Systematic literature analysis, (2) Meta-analysis of the
      randomised-controlled studies (RCTs). RESULTS: (1) The efficacy of 5-FU/SA
      therapy was tested in a total of 625 patients (n=8 RCTs) with common warts and
      101 patients (n=4 RCTs) with plantar warts. The therapeutic effect across all
      studies in common warts was 63.4% response (complete healing) for 5-FU/SA vs.
      23.1% for the 5-FU-free controls, respectively. In plantar warts, the response
      was 63.0% vs. 11.0%. (2) A meta-analysis of n=7 RCTs on common warts (n=325
      patients) showed a mean risk difference of 0.42 (CI 0.34-0.50, p < 0.05), thus a
      significant superiority of 5-FU/SA over SA. A comparable result was also found
      for plantar warts. CONCLUSION: The combination of 5-FU and SA is an effective and
      beneficial therapy for common and plantar warts.

PMID- 16281636
TI  - Topical cosmetics and perioral dermatitis.
AB  - BACKGROUND: Perioral dermatitis (PD) is a common dermatological disease whose
      aetiology and pathogenesis remain speculative. Both cosmetics and topical
      corticosteroids have been implicated. PATIENTS AND METHODS: 75 patients with PD
      and 125 randomly selected control patients with negative PD records were included
      in a questionnaire-based study focusing on cosmetics, their use, and topical
      corticosteroids. The patients were assessed for atopy by clinical criteria, prick
      tests and specific IgE against a mixture of aeroallergens (CAP SX 1). RESULTS:
      There were no significant (p < 0.05) differences in facial skin cleansing between
      the two groups except for night-time cleansing, which was performed more often in
      the patient group. The use of skin care products yielded significant differences
      between the patient and control group in respect to skin care in the morning and
      the use of day creams. Otherwise, the groups did not differ in their skin care
      regime (number of skin care products used, type of product, frequency of care).
      The mean monthly expenditure on cosmetic products did not differ significantly
      between the two groups. 25.3% of the patients used topical corticosteroids which
      were initiated in all cases after the onset of the rash. Significantly (p <
      0.001) higher values were found in the patient group regarding history of atopic
      diseases (49.3% vs. 15.2%), prick test reactivity (> or =2 reactive prick tests:
      49.3% vs. 8.0%), and specific IgE against aeroallergens (CAP SX1 classes > or =2:
      50.7% vs. 15.2%). CONCLUSIONS: The often heard argument that PD results mainly
      from external factors is no longer tenable. A variable interaction between
      external (e.g. cosmetics) and intrinsic factors (e.g. atopic constitution)
      appears to lead to PD, perhaps by subclinical repetitive irritation and final
      overtaxing of the reparative capacity of the epithelial barrier function.

PMID- 16281637
TI  - [Acquired reactive perforating collagenosis after curettage of seborrheic
      keratoses].
AB  - Acquired reactive perforating collagenosis (ARPC) developed in an 81-year-old
      woman two weeks after curettage of seborrheic keratoses. Treatment with
      allopurinol and antipruritic ointment was given. After four months, there was
      complete re-epithelialization, leaving atrophic scars.

PMID- 16281638
TI  - [Grover's disease following hemodialysis in a patient with renal failure].
AB  - A 54-year-old woman with polycystic renal disease and renal failure developed
      Grover's disease while undergoing renal dialysis. Grover's disease or transitory
      acantholytic dermatosis is characterized by intensely pruritic, hyperkeratotic,
      succulent papules and plaques located on the trunk. The pathogenesis is unknown;
      genetic factors and actinic damage have been implicated. Medications, heat or
      immunosuppression can worsen the disease. Associations with atopic dermatitis,
      contact dermatitis and asteatotic dermatitis have also been described.
      Differential diagnostic considerations include folliculitis, scabies and
      dermatitis herpetiformis. Therapeutic options include moisturizing agents and
      phototherapy, as well as topical and systemic retinoids. There are only few case
      reports in the literature describing Grover's disease occurring during
      hemodialysis treatment. All such previous patients have been men; ours is the
      first woman.

PMID- 16281639
TI  - [Erythema induratum-nodular vasculitis].

PMID- 16281640
TI  - [Recurrent moles and nasal blisters after radiation therapy in a 71-year old
      woman].

PMID- 16281641
TI  - [Polymorphous light dermatoses].

PMID- 16281642
TI  - [Systemic therapy of cutaneous lupus erythematosus].

PMID- 16281643
TI  - Small is beautiful: but may be breathless.

PMID- 16281644
TI  - Emotional and behavioural problems in Swedish 7- to 9-year olds with asthma.
AB  - BACKGROUND: The purpose of this study is to compare emotional and behavioural
      problems between preadolescent children with asthma and healthy children, and to
      explore if disease factors relate to problem scores. DESIGN: This was a cross
      sectional study of 59 children, 34 boys and 25 girls, aged 7-9 years with mild (n
      = 11), moderate (n = 38) or severe (n = 10) asthma. A normative sample of 306
      children in the same age range, 150 boys and 156 girls, was used as a comparison
      group. METHODS: Parents assessed emotional and behavioural problems using the
      Child Behaviour Checklist. Peak expiratory flow rate and urinary eosinophil
      protein X were used as measures of lung function and inflammation. Children were
      interviewed about activity restriction and symptoms during the last week using
      the Paediatric Asthma Quality of Life Questionnaire. Parents scored day, night
      and exercise-induced symptoms during the same week. RESULTS: On average, children
      with asthma were attributed more problems than healthy children of the same age
      and comparable family socio-economic status. Effect sizes were 0.80 (95%
      confidence interval 0.52-1.09) for total problems, 0.89 (0.60-1.18) for
      internalizing problems and 0.67 (0.38-0.95) for externalizing problems. The
      relative risk for children with asthma exceeding the 95% cut-offpoint for total
      problems was 4.2 (2.1-8.3) compared to healthy children. CONCLUSION: Children
      with parent-reported exercise-induced asthma symptoms were attributed more total
      problems than asthmatic children without such symptoms. Parent-reported day
      symptoms and child report of symptoms and restricted activities related with
      problem scores to a lesser degree. Objective measures of lung function and
      inflammation were not related to problem scores. Concurrent eczema increased
      problem scores. It is concluded that asthma in preadolescent children is
      associated with emotional and behavioural problems. Special attention should be
      paid to children reported to have exercise-induced symptoms.

PMID- 16281645
TI  - Care plans for acutely deteriorating COPD: a randomized controlled trial.
AB  - INTRODUCTION: Acute exacerbations of chronic obstructive pulmonary disease (COPD)
      are a frequent reason for admission to hospital and are responsible for the
      majority of the direct economic costs of treating COPD. AIMS: To test whether an
      individualized care plan for patients experiencing acute exacerbations of COPD
      result in reduced health care utilization and improved quality of life for
      patients. METHODS: Ninety-two patients with confirmed COPD were selected by
      general practitioners or district nurses, and randomly assigned to care plan or
      usual care groups. The care plan was developed in collaboration with general
      practitioners, secondary care specialists, specialist nurses, ambulance service
      providers and the after hours clinic. Patients were followed for 12 months, and
      the primary end-points were frequency of use of primary care services and
      hospital admissions. RESULTS: There was no significant reduction in hospital
      admissions or improvement in quality of life in the group of patients who used
      the care plan compared to controls. The care plan group called out the ambulance
      service more frequently [2.8 (1.3, 4.3) versus 1.1 (0.7, 1.5) calls per 12
      months; P = 0.03], and there was a trend towards greater use of oral prednisone
      [2.3 (1.4, 3.2) versus 1.3 (0.8, 1.8) courses per 12 months; P = 0.06].
      CONCLUSION: In contrast to asthma, the provision of individualized self
      management plans, whose content was enhanced to provide guidance to carers and
      health care professionals, did not reduce health care utilization or improve
      overall quality of life during acute exacerbations of COPD. Other strategies are
      required.

PMID- 16281646
TI  - Reduction in resting energy expenditure following lung volume reduction surgery
      in subjects with chronic obstructive pulmonary disease.
AB  - STUDY OBJECTIVES: Some subjects with COPD have an elevated resting energy
      expenditure (REE) which may be related to an increased work of breathing at rest.
      The purpose of this study was to examine the effect of lung volume reduction
      surgery (LVRS) on REE and body weight. DESIGN: Ten subjects with COPD were
      recruited (mean age +/- SD = 61.4 +/- 6.1 years). At baseline (which was
      following preoperative pulmonary rehabilitation) and four months following LVRS
      (combined with postoperative pulmonary rehabilitation), each subject had tests of
      lung function, REE via indirect calorimetry using a canopy system, six minute
      walk distance (6MWD) and quality of life (QoL) using the St George's Hospital
      Respiratory Questionnaire (SGRQ). MEASUREMENTS: The FEV1 (% predicted) increased
      from 27.7 +/- 5.8% (mean +/- SD) at baseline to 33.9 +/- 7.8% following LVRS (P <
      0.05). REE (% predicted) was 110 +/- 9.8% at baseline and decreased to 106 +/-
      6.7% following LVRS (P = 0.04). Body mass index (BMI) following LVRS was
      unchanged (P = 0.67). No correlation between the change in BMI and change in REE
      was shown (r2 = 0.3, P = 0.1). There was a significant improvement in QoL
      following LVRS (P < 0.001). 6MWD also significantly increased from 354 +/- 83 m
      to 412 +/- 82 m following LVRS (P = 0.001). CONCLUSION: Whilst there was an
      increase in lung function and a reduction in REE following LVRS, there was no
      corresponding change to body weight. The improvement in REE following LVRS may be
      related to an improvement in work of breathing.

PMID- 16281647
TI  - Establishing a diagnosis of cystic fibrosis.
AB  - Cystic fibrosis (CF) is a recessively inherited condition caused by mutation of
      the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
      Characterization of the genetic defect has improved understanding of the
      condition and, in the majority of cases, diagnosis is straightforward. However,
      in a significant number, diagnosis remains a challenge. This paper will discuss
      the management of these issues and reflect on atypical presentations. In addition
      we will discuss situations in which genetic variations of the CFTR gene are not
      associated with a classical CF phenotype and the implications for practice in
      both paediatric and adult clinics.

PMID- 16281648
TI  - Anxiety and self-management behaviour in chronic obstructive pulmonary disease:
      what has been learned?
AB  - A considerable amount of literature has described the prevalence of anxiety in
      patients with the lung condition chronic obstructive pulmonary disease (COPD).
      Few, if any, papers have reviewed the interrelationship between anxiety symptoms
      and self-management interventions in this population. This is the aim of the
      current review. First, the review examines the evidence suggesting that anxiety
      is more common in COPD than other populations. Secondly, the focus shifts to
      evaluating the evidence for and against the efficacy of COPD self-management
      programmes. Finally this paper examines the relationship between anxiety and COPD
      self-management with particular reference to the benefits and possible harm of
      some COPD self-management goals and anxious patients.

PMID- 16281649
TI  - Essential communication skills in individual smoking cessation.
AB  - When dealing with smokers it is important to realize that nicotine addiction
      plays a major role. Minimal clinic smoking cessation advice by a physician is a
      powerful motivation to quit and even short intervention (<3 minutes) is effective
      especially when repeated. There is a dose-response relationship between the
      number and duration of sessions and quit rate. The optimum programme contains 4-5
      sessions of 10-15 minutes duration during the first six weeks after quit day. It
      is essential that smokers select a target quit day and stop smoking completely on
      that day as even a few cigarettes per day in the first weeks are strongly related
      to relapse. Administration of nicotine replacement products or bupropion may
      double success rates. The communication with smokers should be emphatic and
      adjusted to the level of change. Barriers to successful smoking cessation and
      structured interventions are described. The use of the five As to motivated
      smokers and the five Rs to smokers not ready to quit is recommended. Telephone
      and written material may supplement clinic visits in the follow-up period.

PMID- 16281650
TI  - 'Papillomatization' and 'malignant transformation' of an abscess cavity in a 25
      year old man with recurrent respiratory papillomatosis who may have had Lemierre
      syndrome.
AB  - We report here an unusual case of a 25-year old male with juvenile onset
      recurrent respiratory papillomatosis who developed an infestation of papillomata
      'papillomatization' of an old abscess cavity that, when removed, was coincidently
      found to contain a 2 cm well differentiated squamous cell carcinoma. The abscess
      cavity had been caused by a previous Fusobaterium necrophorum infection that
      probably developed as a result of septic emboli from his internal jugular veins.
      This once common but now rare occurrence was first reported by Dr Lemierre in
      1936 (Lemierre syndrome).

PMID- 16281651
TI  - Clinical trials of airway clearance techniques.

PMID- 16281652
TI  - How good is the evidence for ambulatory oxygen in chronic obstructive pulmonary
      disease.

PMID- 16281653
TI  - Airway clearance in bronchiectasis: a randomized crossover trial of active cycle
      of breathing techniques (incorporating postural drainage and vibration) versus
      test of incremental respiratory endurance.
AB  - OBJECTIVES: The purpose of this study was to compare the efficacy of the test of
      incremental respiratory endurance (TIRE) with active cycle of breathing
      techniques (ACBT) [incorporating postural drainage (PD) and vibration] as methods
      of airway clearance in adults with bronchiectasis. DESIGN: A randomized crossover
      study in which a single session of ACBT (incorporating PD and vibration) was
      compared to a single session of TIRE was carried out in 20 patients (14 female)
      with stable, productive bronchiectasis. MEASUREMENTS: Weight of sputum (treatment
      plus 30 min) was the primary outcome measure recorded. Pre- and post-treatment
      measures of lung function and SpO2 were also recorded. RESULTS: All 20 patients
      were stable during the study period. Sputum weight expectorated during and 30 min
      post-ACBT (incorporating PD and vibration) treatment was significantly greater
      than the sputum weight expectorated during and 30 min post-TIRE treatment [mean
      difference 2.44 g (95% CI 0.43-4.45)]. CONCLUSION: ACBT (incorporating PD and
      vibration) is a more effective method of airway clearance in bronchiectasis than
      TIRE during single treatment sessions.

PMID- 16281654
TI  - Randomized controlled trial of alendronate in airways disease and low bone
      mineral density.
AB  - BACKGROUND: Patients with airways disease have been demonstrated to be at risk of
      osteoporosis, and this is likely to be multifactorial. Our aim was to identify
      patients with low bone mineral density (BMD) using a screening program, and then
      evaluate the benefit of daily alendronate. METHOD: Subjects with hip or lumbar
      spine baseline T-scores < - 2.5, or Z-score < - 1.0 commenced on
      alendronate/calcium (10 mg/600 mg day) or placebo/calcium, in a double blind
      randomized controlled trial. BMD by dual emission X-ray absorptiometry (lumbar
      vertebrae 2-4, neck of femur, total femur) was repeated after 12 months, with
      adverse events recorded. RESULTS: 145 subjects (74 male, 71 female, mean age 67,
      median FEV1 1.0 litres = 43% of predicted) were enrolled; 66 alendronate/calcium,
      79 placebo/calcium with 24 and 26 withdrawals, respectively. Per protocol but not
      intention to treat analysis of covariance demonstrated statistically significant
      improvements in T and Z scores for lumbar spine bone mineral density (P = 0.035,
      P = 0.040), with no improvement demonstrated at the hip. CONCLUSIONS: Improvement
      in bone mineral density has been demonstrated at the lumbar spine, but not hip,
      by per protocol analysis, with daily alendronate, at 12 months.

PMID- 16281655
TI  - Prescribing practice for intermittent oxygen therapy: a GP survey.
AB  - INTRODUCTION: UK figures show that the prescription of home oxygen cylinders for
      intermittent use is substantial. AIM: To examine GP assessment criteria and
      prescribing practice for intermittent oxygen therapy in patients with a diagnosis
      of chronic obstructive pulmonary disease (COPD) in Northern Ireland. METHODS: A
      postal questionnaire was sent to all GPs (n = 534) in two health boards who had
      prescribed cylinder oxygen in a six month period prior to the study. The
      questionnaire was piloted to establish reliability and validity. RESULTS:
      Completed questionnaires were returned by 52% (280/534) of GPs. GPs 'most
      frequently' used advice from hospital specialists [82% (230/280)] to determine
      the need for intermittent oxygen. Criteria such as breathlessness score on
      exercise (e.g., BORG), oximetry on exercise, local guidelines or national
      guidelines were used less frequently or never. CONCLUSIONS: Most patients are
      likely to have been prescribed intermittent oxygen without any objective
      assessment. Implementation of evidence-based guidelines and a formal oxygen
      assessment service, would rationalize the use of intermittent oxygen therapy and
      enable better targeting of this expensive resource.

PMID- 16281656
TI  - High versus low intensity exercise training in pulmonary rehabilitation: is more
      better?
AB  - BACKGROUND: Exercise training is considered a necessary component of
      comprehensive pulmonary rehabilitation. However, to date, there is no consensus
      on an exercise training strategy for pulmonary rehabilitation, and this has
      resulted in varied approaches to this intervention in its literature. As in
      healthy individuals, the effect of exercise training on patients with chronic
      lung disease is dose dependent, with higher intensities resulting in greater
      physiological adaptations than lower intensities. RESULTS: It is not clear from
      our review of the literature that these enhanced physiological effects from
      higher levels of exercise training translate into a reduced burden of symptoms,
      hence a better quality of life. Indeed, there is some evidence that pulmonary
      rehabilitation approaches incorporating lower intensities of exercise training
      are at least as good in improving questionnaire rated symptoms of health status.
      This provides food for thought, since the prominent goal of pulmonary
      rehabilitation should be to reduce bothersome symptoms or enhance health status,
      not simply increase endurance time on a cycle ergometer.

PMID- 16281657
TI  - Crosscultural communication in those with airway diseases.
AB  - Transcultural consultations are becoming commonplace. Such consultations arise
      because patients from ethnic groups consult doctors, but also because patients
      consult doctors from other ethnic backgrounds. Such consultations require a
      cultural awareness and sensitivity which may be particularly necessary when
      concerning those with respiratory illnesses which are often long-term and about
      which there may be considerable stigma. The prevalence of respiratory disease can
      vary between ethnic groups, most noticeably in tuberculosis and smoking; and in
      diseases such as asthma, health service usage and treatment can vary
      significantly with ethnicity. Some of this may represent cultural, rather than
      disease specific differences. Good communication is essential throughout medical
      practice, but in transcultural consultations it is especially important that the
      doctor pays appropriate attention to likely patient beliefs and approaches to
      shared decision making. Usual negotiation regarding goals and outcomes first
      requires the clinician to understand how a patient's understanding of illness may
      vary from a traditional western scientific approach. Special attention needs to
      be paid to the optimal way of using interpreters and more time is often needed
      for crosscultural consultations. Specific training is necessary for health
      practitioners to enable them to acquire the skills for crosscultural care and
      this involves learning about other cultures and an appreciation of how a change
      in attitude often needs to be incorporated into the clinical approach. Acquiring
      these skills and understandings to facilitate optimal transcultural consultation
      enables transfer of these skills to other similar clinical scenarios such as the
      approach to those with disability. The global burden of long-term respiratory
      disease, both infectious and noncommunicable, coupled with increased migration
      and geographical mobility means that a successful crosscultural approach is now a
      priority area for attention.

PMID- 16281658
TI  - Breathing techniques in patients with chronic obstructive pulmonary disease
      (COPD).
AB  - BACKGROUND: Breathing techniques are included in the rehabilitation program of
      patients with chronic obstructive pulmonary disease (COPD). The efficacy of
      breathing techniques aiming at improving symptoms of dyspnea and eliciting
      physiological effects is discussed in this paper. In patients with COPD,
      breathing techniques aim to relieve symptoms and ameliorate adverse physiological
      effects by: 1) increasing strength and endurance of the respiratory muscles; 2)
      optimizing the pattern of thoracoabdominal motion; and 3) reducing dynamic
      hyperinflation of the rib cage and improving gas exchange. Evidence exists to
      support the effectiveness of pursed lips breathing, forward leaning position,
      active expiration and inspiratory muscle training, but not for diaphragmatic
      breathing. Careful patient selection, proper and repeated instruction and control
      of the techniques, and assessment of the effects are necessary. Despite the
      evidence that breathing techniques are effective, several problems need to be
      resolved. The limited evidence for the transfer of the effects of breathing
      techniques during resting conditions to exercise conditions raises several
      questions. Do breathing techniques have to be practiced during activities of
      daily living?

PMID- 16281659
TI  - Chronic bronchitis: should it worry us?
AB  - BACKGROUND: Chronic bronchitis (CB) has been studied using standardized
      questionnaires for decades. From being the key element in the 'British
      hypothesis' chronic bronchitis was reduced to being an innocent disorder in the
      1980s. However, there is now good evidence that chronic bronchitis is associated
      with an increased risk from both overall and chronic obstructive pulmonary
      disease (COPD) specific mortality. Presumably through increasing the frequency of
      lower respiratory tract infections chronic bronchitis is associated with excess
      decline in lung function, hospital admission and other disease specific outcomes.
      The prevalence of chronic bronchitis increases with increasing age and the burden
      associated with chronic bronchitis in this growing proportion of the population
      is large. Vital prognosis in the elderly is affected by CB and this condition
      presumably deserves more attention from the medical profession.

PMID- 16281660
TI  - Why do we need another respiratory journal?

PMID- 16281661
TI  - Lung volume reduction surgery: where are we now?

PMID- 16281662
TI  - Not all self-management programs in chronic obstructive pulmonary disease have
      positive results: why is replication a problem?

PMID- 16281663
TI  - Economic evaluation of a comprehensive self-management programme in patients with
      moderate to severe chronic obstructive pulmonary disease.
AB  - AIMS: The main objective of this study was to investigate whether a comprehensive
      self-management programme, including self-treatment guidelines for exacerbations
      and a fitness programme, is an efficient treatment option for chronic obstructive
      pulmonary disease (COPD) patients. METHOD: We randomly allocated 248 COPD
      patients to either self-management (127) or usual care (121). Data on preference
      based utilities (EuroQol-5D), health-related quality of life (HRQoL), health-care
      resource use and productivity losses associated with exacerbations were
      prospectively collected. Quality-adjusted life years (QALYs) were calculated. The
      economic analysis took the societal perspective and the observation period was
      one year. RESULTS: As we observed that the groups were equally effective in terms
      of QALYs and HRQoL (SGRQ), we described a cost minimization analysis only. The
      self-management programme-specific costs amounted to Euro 642 per patient. In the
      base-case cost analysis, the incremental cost difference amounted to Euro 838 per
      patient per year in favour of usual care. When only direct medical costs were
      included, the incremental annual cost of self-management relative to usual care
      was Euro 179 per person per year. If time costs for the fitness programme were
      set to zero, the costs for self-management diminished to Euro 542. Sensitivity
      analysis showed that these results were robust to changes in the underlying
      assumptions. CONCLUSION: We conclude that the COPE self-management programme is
      not an efficient treatment option for moderate to severe COPD patients who rate
      their HRQoL relatively high. The programme was twice as expensive as usual care
      and had no measurable beneficial effects on QALYs or HRQoL.

PMID- 16281664
TI  - Impact on readmission rates and mortality of a chronic obstructive pulmonary
      disease inpatient management guideline.
AB  - AIMS: Chronic obstructive pulmonary disease (COPD) is a common condition
      associated with considerable morbidity, mortality and hospital admissions.
      However, published COPD management guidelines have major limitations and lack
      practical summaries. We aimed to optimally develop, implement, and evaluate a
      multidisciplinary COPD inpatient management 'ACCORD' guideline, including prompts
      for comprehensive day one assessments through to a discharge criteria checklist.
      METHOD: Two intervention and two control public teaching hospitals in Adelaide,
      South Australia, took part, with pre-intervention (721 COPD admissions over 7
      months) and intervention phases (509 COPD admissions over 7 months). During the
      intervention stage the ACCORD guideline was placed in the case notes on the day
      of admission or soon after. Readmissions were categorized as either emergency or
      elective and compared between the study arms, as were mortality and potential
      confounders (age, gender, number of comorbidities), with Poisson regression
      analysis. RESULTS: Of case notes of eligible COPD patients, 60% had the ACCORD
      guideline placed, of which 76% had evidence of use as judged by completion of
      guideline entry and tick boxes. The ACCORD guideline was associated with an
      increase in elective admissions and a reduction in emergency admissions in the
      intervention group in relation to the control group (P < 0.01), with no
      difference in overall admissions or death rates. CONCLUSIONS: The ACCORD
      guideline was associated with a shift from emergency admissions to more planned
      elective care, suggesting more proactive care of health problems, but without
      overall reduction in admissions.

PMID- 16281665
TI  - Measurement of dyspnea in chronic obstructive pulmonary disease: what is the tool
      telling you?
AB  - AIMS: Dyspnea is the most common symptom experienced by patients with chronic
      obstructive pulmonary disease (COPD) and is linked to decreases in patient
      activity levels and quality of life. Use of standardized tools to measure dyspnea
      has a long history in respiratory care. However, in many cases it is not clear
      what is being quantified when using a particular tool. This review will consider
      the definition of and mechanisms believed to contribute to dyspnea, attempting to
      clarify what is being quantified in common tools currently available for dyspnea
      measurement.

PMID- 16281666
TI  - Endurance versus strength training in chronic obstructive pulmonary disease: 1)
      Endurance training.

PMID- 16281667
TI  - Endurance versus strength training in chronic obstructive pulmonary disease: 2)
      Resistance training.

PMID- 16281668
TI  - Intensive care and invasive ventilation in the elderly patient, implications of
      chronic lung disease and comorbidities.
AB  - AIMS: Elderly patients have an increasing prevalence of illness that requires
      consideration of critical care and invasive ventilatory support. Although
      critical care of even the very elderly can provide value, with increasing age the
      potential risks of treatment and diminishing returns with respect to quality and
      quantity of life result in a need for careful evaluation. Variable combinations
      of impaired organ function, active disease and residual pathology from past
      disease and injury all affect critical care, with the consequence that the
      elderly are a very heterogeneous population. Recognizing that critical care is a
      limited resource, it is important to identify patients who may be at increased
      risk or least likely to benefit from treatment. Patients with functional
      impairments, nutritional deficiencies and multiple comorbidities may be at
      highest risk of poor outcomes. Those with very severe disease, extreme age and
      requirements for prolonged ventilatory support have high in-hospital mortality.
      Functional impairments, comorbidities and severity of illness are usually more
      important considerations than chronologic age. The objective of this review is to
      identify how common problems of the elderly affect critical care and decisions
      concerning use of invasive ventilatory support.

PMID- 16281669
TI  - Living and dying with respiratory failure: facilitating decision making.
AB  - Respiratory failure is a predictable cause of death in end stage lung disease
      including COPD and neuromuscular disorders, and the symptom burden for these
      individuals in the last six months of life is significant. Palliative care
      services are less well-developed for patients with chronic disorders compared to
      those with malignant disease; and communication problems can be compounded by a
      mismatch in expectations between patients and health care providers on prognosis
      and other issues. Most patients want more information about their illness to
      facilitate participation in decision making. Noninvasive ventilation may extend
      life and palliate symptoms in neuromuscular disorders such as Duchenne muscular
      dystrophy and motor neurone disease/ALS.

PMID- 16281670
TI  - Use of hypnotics in patients with chronic obstructive pulmonary disease.

PMID- 16281671
TI  - Cancer in the US Associated Pacific Islands (UASPI): history and participatory
      development.
AB  - The US-associated Pacific Island jurisdictions (USAPI) have great disparities in
      health care and comprehensive cancer care compared to the United States. Cancer
      mortality ranks first or second among the leading causes of death in most of
      these island nations. The USAPI has formed the Cancer Council of the Pacific
      Islands (CCPI), an indigenous council to identify and address the cancer health
      disparities of the region. The CCPI efforts were formally launched in 2002 with
      the support of the Center to Reduce Cancer Health Disparities, a Center of the
      National Cancer Institute (CRCHD-NCI) and the National Center for Minority Health
      Disparities, a Center of the National Institutes of Health (NCMHD-NIH).
      Facilitating partners are the Department of Family Medicine and Community Health,
      University of Hawai'i and 'Imi Hale - Native Hawaiian Cancer Network, a program
      of Papa Ola Lokahi. The objectives of this initiative are to describe and address
      the cancer health disparities in the USAPI. Over the past 2 years there has been
      considerable progress in identifying and prioritizing cancer prevention and
      control needs; launching cancer prevention and control efforts in each of the
      jurisdictions; and leveraging additional funding to support ongoing activities.
      The support from the Center to Reduce Cancer Health Disparities in fostering a
      participatory model of development has been landmark in the establishment and
      implementation of this initiative. This manuscript provides a historical
      background on cancer in the USAPI and prefaces 9 cancer assessments in this
      journal from the Commonwealth of the Northern Mariana Islands, Guam, American
      Samoa, Republic of the Marshall Islands, Republic of Belau, and the four states
      (Yap, Pohnpei, Kosrae and Chuuk) of the Federated States of Micronesia.

PMID- 16281672
TI  - Cancer Council of the Pacific Islands: speaking with one voice.

PMID- 16281673
TI  - Cancer in American Samoa.
AB  - This study, funded by the National Cancer Institute, assessed cancer awareness
      and service needs in American Samoa. Cancer is the second-leading cause of death
      in American Samoa, yet cancer specific resources are lacking. Assistance is
      needed to help: 1) increase cancer outreach and community awareness; 2) increase
      the cancer capacity of health professionals; 3) improve laboratory capacity for
      cancer screening and detection; and 4) establish a comprehensive and coordinated
      system of cancer services.

PMID- 16281674
TI  - Cancer in the Commonwealth of the Northern Marianas Islands (CNMI).
AB  - The purpose of this study, funded by the National Cancer Institute, was to
      document the state of cancer awareness and services in the Commonwealth of the
      Northern Mariana Islands (CNMI) and to begin to identify cancer-care needs.
      Findings suggest that cancer is the second-leading cause of death in the CNMI,
      and that the most prevalent cancers are those that can be prevented and/or cured
      with early detection and treatment. Key informants identified a number of cancer
      related service needs, and an action plan was developed based on three priority
      areas: 1) developing a cancer registry; 2) increasing resources dedicated to
      cancer prevention and control programs, and 3) increasing capacity of health
      professionals and support staff.

PMID- 16281675
TI  - Cancer in Chuuk State, Federated States of Micronesia.
AB  - The purpose of this study, funded by the National Cancer Institute, was to
      document the state of cancer awareness and services in Chuuk State, Federated
      States of Micronesia (FSM) and to begin to identify the need for cancer-care
      services. Findings suggest that cancer is the third-leading cause of death in
      Chuuk, yet cancer-related awareness, prevention, detection, and treatment
      services are limited. A number of needs were identified, and an action plan was
      developed based on five priority areas: 1) establishing a cancer registry; 2)
      improving ICD coding skills and knowledge; 3) increasing public awareness about
      cancer; 4) establishing an office dedicated to cancer; and 5) increasing
      screening of high-risk individuals.

PMID- 16281676
TI  - Cancer in Kosrae State, Federated States of Micronesia.
AB  - Little is known about the impact of cancer and the extent of cancer-related
      services in Kosrae. The purpose of this study, funded by the National Cancer
      Institute, was to document the state of cancer awareness and services in Kosrae
      and to begin to identify cancer-care needs. Findings suggest that cancer is the
      eighth-leading cause of death in Kosrae, although a number of factors contribute
      to a possible undercount of cancer cases. Cancer-related services are limited. A
      number of needs were identified, and an action plan was developed based on three
      priority areas: 1) establishing a cancer registry; 2) increasing public awareness
      about cancer risk, prevention, and detection; and 3) expanding cancer screening
      and detection programs.

PMID- 16281677
TI  - Cancer in Pohnpei State, Federated States of Micronesia.
AB  - A cancer needs assessment, funded by the National Cancer Institute, was conducted
      in Pohnpei State (Pohnpei), Federated States of Micronesia (FSM). Findings
      revealed that cancer is the third leading cause of death in Pohnpei, yet cancer
      related awareness, prevention, detection, and treatment services are limited. A
      number of needs were identified, and an action plan was developed based on five
      priority areas: 1) increasing community awareness about cancer (especially,
      cervix, breast, liver and lung) and related risk factors; 2) securing funding for
      cancer prevention and control planning and activities; 3) establishing a fully
      staffed cancer prevention and control office; 4) building local capacity for
      cancer cytology; and 5) increasing capacity to obtain and process lab specimens
      for high-risk patients.

PMID- 16281678
TI  - Cancer in Yap State, Federated States of Micronesia.
AB  - Little is known about the impact of cancer and the extent of cancer-related
      services in Yap. The purpose of this study, funded by the National Cancer
      Institute, was to document the state of cancer awareness and services in Yap and
      to prioritize cancer-care needs. Findings suggest that cancer is the leading
      cause of death in Yap, yet cancer-related awareness, prevention, detection, and
      treatment services are limited. A number of needs were identified, and an action
      plan was developed based on five priority areas: 1) establishing a cancer
      registry; 2) increasing awareness of cancer risk, prevention, and detection; 3)
      expanding cancer screening and detection programs; 4) expanding cancer-related
      training opportunities for clinical staff; and 5) purchasing cancer-related
      equipment & supplies.

PMID- 16281679
TI  - Cancer in the Territory of Guam.
AB  - The purpose of this study, funded by the National Cancer Institute, was to assess
      cancer awareness and service needs in Guam. Guam maintains a cancer registry, and
      data suggest that cancer is the second-leading cause of death in Guam. A chapter
      of the American Cancer Society has been established on the island. Although basic
      cancer diagnosis and treatment services can be provided on Guam, many cancer
      patients must travel to Hawai'i, the U.S. continent, or to Asian countries to
      seek more advanced medical care. This places a severe strain on the island's
      limited financial resources that, in turn, affects all aspects of health care for
      the people of Guam. Key informants identified a number of cancer-related service
      needs, and an action plan was developed based on five priority areas: 1)
      increasing the capacity of cancer prevention and control staff; 2) increasing
      public awareness of cancer risk factors; 3) expanding the capacity of the Guam
      Cancer Registry; 4) establishing a Cancer Prevention and Control Advisory Board
      for the Territory; and 5) improving early detection and screening for priority
      cancers.

PMID- 16281680
TI  - Cancer in the Republic of Palau (Belau).
AB  - This study, funded by the National Cancer Institute, assessed cancer awareness
      and service needs in the Republic of Belau (Belau) in April 2003. Cancer
      prevention and control is a concern for Belau, and this country maintains a
      cancer registry to track cases and outcomes. However, assistance is needed to
      strengthen and expand existing cancer-related services. Key informants requested
      help to develop a comprehensive cancer prevention and control program, increase
      the capacity of professional staff in diagnosing and treating cancer, and improve
      laboratory and pathology services.

PMID- 16281681
TI  - Cancer in the Republic of the Marshall Islands.
AB  - This study, funded by the National Cancer Institute, assessed cancer awareness
      and service needs in the Republic of the Marshall Islands (RMI). Findings suggest
      that cancer is the second-leading cause of death in the RMI and is, in part, a
      consequence of 12 years of nuclear testing in this region of the Pacific.
      However, cancer-related services are lacking. Assistance is needed to establish a
      national cancer registry, to increase public awareness about cancer and related
      risk factors, and to develop and implement a cancer prevention and screening
      program.

PMID- 16281682
TI  - Cancer in Micronesia.
AB  - Between November 1998 and December 1999, trained medical record abstractors
      visited the Micronesian jurisdictions of Chuuk, Kosrae, Pohnpei, and Yap (the
      four states of the Federated States of Micronesia), as well as the Republic of
      Palau (Belau), the Republic of Kiribati, the Republic of the Marshall Islands
      (RMI), and the Republic of Nauru to review all available medical records in order
      to describe the epidemiology of cancer in Micronesia. Annualized age-adjusted,
      site-specific cancer period prevalence rates for individual jurisdictions were
      calculated. Site-specific cancer occurrence in Micronesia follows a pattern
      characteristic of developing nations. At the same time, cancers associated with
      developed countries are also impacting these populations. Recommended are
      jurisdiction-specific plans that outline the steps and resources needed to
      establish or improve local cancer registries; expand cancer awareness and
      screening activities; and improve diagnostic and treatment capacity.

PMID- 16281683
TI  - Cancer epidemiology in the freely associated U.S. Pacific Island jurisdictions:
      challenges and methodologic issues.
AB  - The health care systems of the U.S.-associated Pacific Island jurisdictions,
      especially the three freely associated states (Federated States of Micronesia,
      Republic of the Marshall Islands, and Republic of Belau), are faced with problems
      similar to developing countries such as malnutrition and infectious diseases, as
      well as diseases relating to westernization such as diabetes, heart disease, and
      cancer. Although cancer has emerged as an important cause of morbidity and
      mortality in the Pacific, little population-based data are currently available.
      This paper addresses some of the practical and methodological challenges to
      obtaining accurate and reliable cancer data in these jurisdictions. This paper
      discusses the use of annualized period prevalence to allow for some measurement
      of cancer burden when cancer incidence cannot be accurately calculated. This
      method, however, has its own limitations as cancer prevalence relates to both
      incidence and duration of illness, and numerous factors impact survival potential
      (i.e., preexisting diseases, lifestyle practices, and access to treatment). In
      addition, under-ascertainment and data quality issues will impact any cancer
      morbidity or mortality measurements. Thus, improvement in the health care
      systems, including the creation and ongoing support of active cancer registries
      would be the optimal approach to better delineating cancer occurrence and risk
      for the populations of these Pacific Island jurisdictions.

PMID- 16281684
TI  - Epidemiology of cancer in the Republic of Kiribati.
AB  - Little is known about cancer epidemiology in Kiribati. Between November 1998 and
      December 1999, trained medical record abstractors visited 8 Micronesian
      jurisdictions including the Republic of Kiribati to review all available medical
      records in order to describe the epidemiology of cancer in Micronesia and to
      better understand the cancer data and control systems in each entity. The
      Republic of Kiribati has identified many prevalent preventable cancers. The lack
      of a robust cancer data tracking and surveillance system, as well as the lack of
      resources to institute a technologically and medically sustainable cancer control
      system was apparent. The implementation or existence of a national comprehensive
      cancer control strategic plan would facilitate greater identification,
      prevention, and treatment of cancer patients. The health sector and Government of
      Kiribati are working towards this end.

PMID- 16281685
TI  - Cancer in Pacific people in New Zealand: a descriptive study.
AB  - Non-Maori Pacific people constitute a significant and rapidly growing population
      in New Zealand. An accompanying change in lifestyle associated with changing
      socio-economic environments results in a change in disease patterns including
      cancer. The paucity of reliable data on cancer necessitates our effort to
      contribute to the control of cancer by reviewing the available information. Our
      study indicates a high incidence among non-Maori Pacific people of some cancers
      of public health importance as well as a disproportionately high mortality rate
      compared to non-Maori, non-Pacific people in New Zealand. In addition, we
      challenge previous documentation of a significant and high incidence of cervical
      cancer among Pacific women compared to non-Pacific people in New Zealand. We also
      identified the need to remedy the inadequacy in data quality as part of any
      strategy to prevent and control the rising incidence and mortality attributed to
      cancer among non-Maori Pacific people. In addition we have commenced regional
      training on cancer epidemiology and propose further cancer studies in both New
      Zealand and the Pacific Islands.

PMID- 16281686
TI  - Epidemiology of cancer in the Republic of Nauru.
AB  - Between November 1998 and December 1999, the Republic of Nauru was one of 8
      Micronesian jurisdictions visited by trained medical record abstractors to review
      all available medical records in order to describe the epidemiology of cancer in
      Micronesia and to better understand the cancer data and control systems in each
      entity. There is likely incomplete ascertainment of cancer cases in the Republic
      of Nauru because of historical events, and the lack of a robust cancer registry
      and a systematic cancer surveillance system. A national comprehensive cancer
      control strategic plan and the implementation of that plan would facilitate
      greater prevention, treatment and control of cancer. The government of Nauru is
      working towards this end.

PMID- 16281687
TI  - Smoking rates and risk factors among youth in the Republic of the Marshall
      Islands: results of a school survey.
AB  - Rapidly increasing tobacco use in developing countries will result in a large and
      increasing burden of tobacco-related illnesses as their populations age. The
      Republic of the Marshall Islands (RMI) is an island nation in the Pacific with a
      1999 census population of 50,840, of whom more than fifty percent were under
      twenty years of age. There are limited data on the prevalence of smoking among
      youth in the RMI. A school survey of 3,294 RMI students in grades 5 through 12
      was conducted in 2000. Urban and outer atoll schools were included in the sample.
      Demographic data and information on tobacco use and risk factors were collected.
      The overall smoking rate in this school sample was 10.6%. There were
      significantly higher smoking rates in the high school age group; the rate of
      smoking among 18 year olds was 33.5%. Smoking rates were higher among males
      compared to females (18.7% vs. 3.4%) and higher among outer atoll students
      compared to urban students (14.5% vs. 9.4%). The most prominent risk factors for
      smoking were: age, male gender, receiving or wearing tobacco-labeled equipment or
      clothing and willingness to participate in other high-risk behaviors. The survey
      provides an estimate of smoking rates among Marshallese school students and
      identifies and quantifies significant risk factors for smoking. This information
      can assist in guiding a comprehensive tobacco control strategy in the Republic of
      the Marshall Islands.

PMID- 16281688
TI  - Disparities in outcomes for pediatric cancer patients treated in Hawai'i:
      comparing Hawai'i residents to children referred from the Pacific Islands.
AB  - This article examines whether pediatric cancer patients referred to Hawai'i from
      the Pacific Islands had poorer outcomes than Hawai'i residents treated at the
      same hospital. For children admitted from 1981 to 2002, we obtained data on
      patient demographics and outcomes from a review of medical charts and physician
      case reviews. We found that pediatric cancer patients referred from the Pacific
      Islands for treatment in Hawai'i had a higher relative risk of death, of not
      receiving treatment in a timely manner, of not completing treatment, and of being
      lost to follow-up than pediatric cancer patients that were residents of Hawai'i.
      The higher risk of poor outcomes for pediatric cancer patients referred from the
      Pacific Islands can be addressed by improving the health care systems in both the
      Pacific Islands and in Hawai'i.

PMID- 16281689
TI  - Native Hawaiians mortality, morbidity, and lifestyle: comparing data from 1982,
      1990, and 2000.
AB  - This paper shares 2000 data on Native Hawaiian health and compares the 2000 data
      with data from 1982 and 1990. The findings suggest that Native Hawaiians continue
      to die at younger ages than Hawai'i residents in other ethnic groups, have a
      higher prevalence of hypertension, diabetes, and asthma than other ethnic groups,
      and have higher rates of smoking, drinking, and being overweight. Compared to
      earlier years, however, smoking and drinking prevalence has decreased, and more
      Native Hawaiians are getting physical exams and other screening exams. These
      improvements may be related to increases in Native Hawaiian health professionals,
      supported by the Native Hawaiian Health Scholarship Program, and to increased
      access to health education and to care through outreach programs such as the
      Native Hawaiian Health Care Systems and the Breast and Cervical Cancer Control
      Program. If these programs are allowed to continue and to expand, we should see
      an improvement in overall health status of Native Hawaiians.

PMID- 16281690
TI  - Tobacco use prevention and control: implications for Native Hawaiian communities.
AB  - Despite the fact that the State of Hawai'i has the second lowest smoking
      prevalence rate in the nation, a higher proportion of Native Hawaiians continue
      to smoke cigarettes. Three data sources are examined and reveal that tobacco use
      and the health impact of tobacco use disproportionately affects Native Hawaiian
      adults and youths in Hawai'i. Studies have documented that dissemination of the
      approaches and methods shown to be effective will reduce the number of young
      people who become addicted to tobacco, increase the success rate of people trying
      to quit using tobacco, decrease the exposure of nonsmokers to environmental
      tobacco smoke, and decrease the burden of tobacco-related diseases and death.
      Strategies recommended for reducing tobacco use among Native Hawaiians include:
      (1) the development of collaboration with local school districts to implement
      school-based prevention programs in conjunction with community-based and media
      based activities and (2) the Native Hawaiian Health Programs developing
      activities to implement the "5 A's" for brief clinical interventions.

PMID- 16281691
TI  - Demographic, treatment, and survival patterns for Native Hawaiians with lung
      cancer treated at a community medical center from 1995 to 2001.
AB  - Lung cancer is the leading cause of death from cancer among persons of Native
      Hawaiian ancestry. Because a large number of Native Hawaiian patients with cancer
      are treated at this hospital, a single-institution review was conducted to
      compare recent non-small cell lung cancer (NSCLC) survival and treatment patterns
      in Native Hawaiian and non-Native Hawaiian patients. A total of 1,394 cases of
      NSCLC registered between January 1995 and December 2001 were reviewed; of those,
      229 patients self-reported Native Hawaiian ancestry. Independent predictors of
      survival were determined by proportional hazards regression modeling. The median
      age at diagnosis for all cases of NSCLC, and for males and females separately,
      was significantly lower for Native Hawaiian vs. non-Native Hawaiian patients.
      Although there were no significant differences in the distribution of cancer
      stage, the median age at diagnosis at each stage was also significantly lower for
      Native Hawaiian vs. non-Native Hawaiian patients. A higher proportion of patients
      were women in the Native Hawaiian group. Differences in the time to receiving
      primary treatment, or the proportions receiving surgery, radiation therapy, or
      chemotherapy, for each stage of disease, were not significant. Controlling for
      age, gender, stage and Native Hawaiian ancestry was associated with an increased
      mortality risk. An observed higher mortality risk from NSCLC for Native Hawaiians
      was not associated with differences in treatment as appropriate for stage, nor
      with delays in treatment; this suggests other factors, including environmental or
      biological influences, as contributors to unfavorable lung cancer outcomes among
      Native Hawaiians.

PMID- 16281692
TI  - Ethnic differences in breast cancer in Hawai'i: age, stage, hormone receptor
      status, and survival.
AB  - Previous examinations of breast cancer and survival in Hawai'i's 5 major ethnic
      groups have found that Native Hawaiian women have the highest breast cancer
      mortality rates. Although ethnic disparities in survival are reduced when age and
      stage at diagnosis are controlled for statistically, prior studies could not
      explain ethnic variation in survival among women who were diagnosed at the same
      stage. We examined variations in breast tumor characteristics for a multiethnic
      sample of 4,583 women diagnosed in 1990-1997 by stage and age group and extended
      previous multivariate analyses by adding a new prognostic variable: estrogen
      receptor (ER) and progesterone receptor (PR) status. Logistic regression was used
      to examine the influence of age, stage, and hormone status on 5-year survival.
      With a few exceptions, greater proportions of Native Hawaiian women were
      diagnosed both in later stages of disease and at earlier ages compared to women
      of other ethnicities, and smaller proportions of Native Hawaiians survived 5
      years post diagnosis in each stage and age group. Surprisingly, greater
      proportions of Native Hawaiian women in all age groups had ER/PR positive tumors,
      which is a prognostic indicator for better, not worse, survival. Native Hawaiian
      women had an increased risk of death and Japanese women had an increased chance
      of survival after controlling for age, stage, and ER/PR status. Future studies
      should examine other reasons for better survival of Japanese women and worse
      survival of Native Hawaiian women, including socioeconomic status, access to
      health insurance, adequacy of recommended screening frequency, co-morbid
      conditions, treatment appropriateness and compliance, and genetic markers of
      tumor aggressiveness.

PMID- 16281693
TI  - Native Hawaiian preferences for informed consent and disclosure of results from
      research using stored biological specimens.
AB  - Increasingly, genetic and biomedical researchers are developing protocols to
      reexamine human tissue specimens that were obtained and stored during clinical
      care or previous research studies. Although some communities and associations are
      developing guidelines for human-tissue research, guideline development rarely
      considers consumer preferences for informed consent and disclosure of results.
      This study, examining Native Hawaiian preferences for informed consent and
      disclosure of results (n = 429, 83.2% Native Hawaiian), was modeled after a
      national study of consumer preferences, allowing comparison between the national
      sample and the Hawai'i-based sample. The interview schedule included two
      scenarios on research requiring the re-use of clinically derived and research
      derived biological specimens. For each, participants were asked if informed
      consent should be required: a) in general; b) if the specimen was personally
      identified; and c) if the specimen was de-identified, or anonymized. Participants
      were also asked if they would want to know the results of the research and if
      they would want their doctor to be told. Regardless of how specimens were
      obtained, 78% of Native Hawaiians would want to be asked for their consent for
      the re-use of identified specimens and about 35% would want to be consented for
      the re-use of anonymized specimens. In both cases, Native Hawaiians in the
      Hawai'i sample were more likely than Whites in the national sample to want an
      informed consent process. Similar proportions in both samples would want findings
      from research on stored specimens reported to them (about 90%) and to their
      physicians (about 80%). These findings call into question the "Common Rule" and
      the guidelines of the American Society of Human Genetics, which do not require
      researchers to obtain informed consent for research use of anonymized specimens.

PMID- 16281694
TI  - Primary care physicians' knowledge, attitudes and practices related to cancer
      screening and cancer prevention clinical trials.
AB  - Native Hawaiians have high cancer incidence and mortality rates, thus would
      benefit from timely cancer screening and opportunities to participate in cancer
      prevention clinical trials. Two-hundred-fifty-four (254) primary care physicians
      (PCPs) were surveyed for their knowledge, attitudes, and practices related to
      cancer screening and prevention, clinical trials and participation of Native
      Hawaiians in them. More than 90% of responding PCPs follow guidelines for breast
      and cervical cancer screening and counsel patients on smoking cessation, and 75%
      or greater follow guidelines for colonoscopy/sigmoidoscopy testing and counsel
      patients on exercise, diet, and weight management. About 60% reported familiarity
      with at least one of three prevention trials offered at the time of the survey,
      and 28% reported having referred or recommended patients to cancer prevention
      trials in the past. Major barriers to discussing trials with patients included
      lack of awareness on the part of physicians and patients, limited support staff,
      and time constraints. Less than 30% of respondents were aware of community
      resources supporting cancer research. This study indicated that Hawai'i PCPs
      follow national guidelines for cancer screening, and many are aware of ongoing
      prevention trials. However, additional participation in cancer screening and
      prevention activities will require attention to reducing logistical barriers and
      increasing awareness of cancer information and research services.

PMID- 16281695
TI  - Ka Lokahi Wahine: a culturally based training for health professionals.
AB  - Native Hawaiian women in Hawai'i suffer the highest breast cancer incidence and
      death rates among women from Hawai'i's five major ethnic groups. Native Hawaiian
      women have the third highest breast cancer mortality rate in the nation,
      following African American and Native American/Alaska Native women. While overall
      cancer mortality rates in other U.S. populations have improved, epidemiological
      research shows mortality rates among Native Hawaiians has dramatically increased
      since 1976. Several barriers prevent Native Hawaiian entry into health care.
      Frequently cited barriers are: a history of oppression; high prevalence of
      behavioral risk factors; ineffective screening, prevention and treatment efforts;
      poor utilization of existing services; poor financial and geographical access to
      care; an absence of culturally appropriate programs, and few Native Hawaiian
      health professionals. To address poor health service utilization and to sensitize
      the health care system in Hawai'i, the Native Hawaiian Breast Cancer Sub
      Committee (NHBCSC) of the American Cancer Society Hawai'i Pacific, developed and
      implemented a culturally based training for health professionals. The training is
      designed to meet continuing medical and professional education requirements.
      Professional in-service training began in 2001, with over 300 of Hawai'i's health
      care professionals participating, to date (March 2004). This training provides a
      model for other cultural and ethnic groups.

PMID- 16281696
TI  - Increasing participation in cancer research: insights from Native Hawaiian women
      in medically underserved communities.
AB  - The cancer burden falls heavily on Native Hawaiian women, and of particular
      concern are those living in medically underserved communities where participation
      in potentially helpful clinical studies may be limited. Difficulty in accrual of
      Native Hawaiian women to a culturally-grounded intervention led researchers to
      conduct focus groups aimed at exploring attitudes towards research, use of a
      traditional Hawaiian practice for family discussion, and study promotion. Social
      marketing theory guided the development of discussion questions and a survey.
      Through purposive sampling, 30 women from medically underserved communities were
      recruited. Content analysis was used to identify major discussion themes.
      Findings indicate that lack of informational access may be a major barrier to
      participation. Study information disseminated through community channels with
      targeted outreach to social and religious organizations, promotion through face
      to-face contact with researchers, and culturally tailored messages directed to
      families were preferred. Community oriented strategies based on linkages with
      organizational networks may increase participation.

PMID- 16281697
TI  - Factors associated with health-seeking behaviors of Native Hawaiian men.
AB  - Native Hawaiian men have higher mortality rates and lower life expectancies than
      Caucasian men in the United States and in Hawai'i. As an initial step in
      developing targeted cancer awareness interventions for Native Hawaiian men, the
      Native Hawaiian Cancer Committee (NHCC) of the American Cancer Society Hawai'i
      Pacific, Inc. conducted focus groups of Native Hawaiian men living in four
      geographical areas in Hawai'i in 2002-2003. The purpose was to explore attitudes
      and practices related to health-seeking behaviors among Native Hawaiian men. In
      all, 54 urban- and rural-dwelling men participated. Many common issues related to
      access to care, perceptions, attitudes, as well as cultural values were
      identified. These findings provide opportunities to motivate Hawaiian men to
      navigate the current healthcare system and facilitate access to healthcare.
      Integrating cultural strengths and preferences into health-seeking approaches can
      readily affect behaviors, and with time, improve the health status of Native
      Hawaiian men.

PMID- 16281698
TI  - Ethnic identities and lifestyles in a multi-ethnic cancer patient population.
AB  - This report examined ethnic identity in 367 recently diagnosed cancer patients in
      Hawai'i's primary ethnic groups: Japanese, Hawaiians, Europeans, and Filipinos.
      The study assessed ethnic self-identify; definitions of and participation in
      different ethnic lifestyles; and relationships between measures of ethnic self
      identity, lifestyle, and other indicators of ethnic and cultural affiliations.
      Results indicated that medical record-based ethnic indicators were well linked to
      individual self-reports of family pedigree. Self-descriptors included non
      standard terms such as "American" and "Local," and respondents reported following
      between five and six different ethnically-associated ways of life. Multivariate
      analysis indicated that ethnic self-identity made a unique contribution that went
      beyond standard ethnic and acculturative markers in explaining lifestyles. This
      study provides strong support for multiculturalism in this ethnically
      heterogeneous population.

PMID- 16281699
TI  - Health research in the Pacific.
AB  - The Pacific Island countries are geographically scattered, with contrasting
      environmental, social, and political systems, and in varying stages of economic
      development, but all are going through a rapid epidemiological transition.
      Processes that took place over thousands of years in Western countries have been
      very much compacted in time in the Pacific. These processes have produced major
      changes in environment and lifestyle, which have produced epidemics of non
      communicable disease. While it is important to consider non-communicable diseases
      as a group, it is also important to conduct research into their specific causes.
      There has been a great deal of research into cardiovascular disease and diabetes
      in the Pacific, but it is only recently that the importance of cancer as a major
      source of mortality and morbidity in the Pacific has been recognised, even though
      it appears to carry a similar burden of morbidity and mortality. It is therefore
      important that research into the causes and control of cancer in the Pacific is
      conducted. However, it is also crucially important that this research both learns
      from the successes and avoids the mistakes of the past. In particular, it is
      crucial that cancer research in the Pacific is not another opportunity for
      "research colonialism," but instead provides opportunities for Pacific-training
      of Pacific health researchers and the conduct of Pacific-led research.

PMID- 16281700
TI  - The 'place' of data.
AB  - Health disparities research has been at the forefront for many researchers,
      organizations, and funding agencies. Collecting, interpreting, and disseminating
      data on particular disparate populations are at the core of this research
      process, data which have been interpreted to be meaningful to the benefit of and
      use by communities. The purpose of this paper is to explore the question, "How is
      data used?" with an appreciation for indigenous beliefs and community based
      research. An analogy, from the perspective of "place," will be used to illustrate
      how data is used through various levels of commitment or belonging one has to a
      particular place. Recommendations on the collection, interpretation and
      dissemination of data from this perspective conclude this paper.

PMID- 16281701
TI  - Time to care.

PMID- 16281702
TI  - The poisoning of 'awa: the non-traditional use of an ancient remedy.
AB  - In the traditional practice of Native Hawaiians, 'awa (Piper methysticum) has
      long been revered as a medicine, a sacred plant central to religious ceremony,
      and a social drink. In the late 1990s, 'awa attracted global attention as an
      herbal alternative to existing pharmaceuticals for reducing stress, anxiety, pain
      and assorted ailments. Marketed since 1994 as a dietary supplement, within seven
      years 'awa had earned the title of a "superstar" and quickly became one of the
      top eight herbal remedies in an expanding $18 billion-plus herbal remedy
      industry. In one study, the plant was even argued to possess chemopreventive
      properties, when cancer incidence and kava consumption in Pacific island
      communities were correlated. In 2002, however, the remedy was banned in several
      European countries, after case reports of liver toxicity allegedly associated
      with its nontraditional use surfaced. In the United States (US), the Food and
      Drug Administration issued a consumer advisory leading several retailers to
      voluntarily withdraw products containing 'awa from their shelves. These actions
      have sent shock waves throughout Pacific Island communities seeking to derive
      economic benefit from a relatively new and little-regulated industry. Moreover,
      they threaten the vitality of centuries of Native Hawaiian cultural practice.
      Clinical studies advocating both sides of the safety debate have been published,
      as producers, marketers and users attempt to influence government action. At the
      same time, issues of cultural exploitation, religious freedom, traditional
      practice, and native intellectual property rights are absent from the debate,
      leaving the future of native practice hanging in the balance. Whether or not the
      herb's status is restored, the situation raises critical questions: Is 'awa
      toxic? Or, does the poison derive from its use outside of traditional practice?

PMID- 16281703
TI  - Cancer, reproductive abnormalities, and diabetes in Micronesia: the effect of
      nuclear testing.
AB  - Many suggest that cancer and other diseases in Micronesia have been caused by
      nuclear testing in the Pacific. The 50-year commemoration of the March 1, 1954
      Bravo thermonuclear test has rekindled interest in this area. This paper explores
      the documentation for, and the plausibility of, claims for disease causation by
      nuclear testing. Given the sheer volume of testing that the US conducted in the
      Pacific, it appears plausible that excess cancer would have occurred in areas of
      Micronesia other than the Marshall Islands. An excess of birth abnormalities in
      the Marshall Islands has been documented. While diabetes is not a radiogenic
      disease, and other cancers are generally less radiogenic than leukemia or thyroid
      cancer, the social and cultural effects of nuclear testing specifically, and the
      strategic uses to which Micronesia has been put generally, have had roles in the
      social production of disease. Integration into a globalized, cosmopolitan economy
      with attendant phenomena such as the importation of tobacco, alcohol, foods of
      poor nutritional value, and new cultural mores-are also factors.

PMID- 16281704
TI  - The Special Populations Networks for cancer awareness research and training.
AB  - The Special Populations Networks (SPN) project is widely regarded as perhaps the
      most successful in the history of the National Cancer Institute (NCI) at
      performing cancer awareness, research, and training activities within minority
      and underserved communities throughout the United States and its territories. Key
      to that success is the trust established among the community, its researchers and
      the NCI. Composed of 18 separate grant awards, the SPN project was implemented in
      April 2000 to integrate the communities' need for cancer information with the
      NCI's need to increase cancer awareness, perform new research, and train minority
      junior investigators for research in populations with a disproportionate burden
      of cancer. To date, the 18 networks have conducted more than 1,000 awareness
      events, trained more than 2,000 community health aides, won 135 grants to support
      pilot research projects, published 130 peer-reviewed papers, and raised another
      $20 million to support SPN activities. Successful implementation of the SPN
      project required the principal investigators to establish and maintain close
      working relationships with key community leaders and organizations in cooperation
      with NCI.

PMID- 16281705
TI  - Na Liko Noelo: a program to develop Native Hawaiian researchers.
AB  - Native Hawaiians are underrepresented in health research. They also have
      expressed dissatisfaction with the way in which many non-native researchers have
      formulated research questions, conducted research, and disseminated findings
      about Native Hawaiians. 'Imi Hale - Native Hawaiian Cancer Network was funded by
      the National Cancer Institute to increase research training and mentorship
      opportunities for Native Hawaiians. To this end, 'Imi Hale has followed
      principles of community-based participatory research to engage community members
      in identifying research priorities and assuring that research is beneficial, and
      not harmful, to Native Hawaiians. Developing indigenous researchers is a
      cornerstone of the program and, in its first 4 years 'Imi Hale enrolled 78 Native
      Hawaiian "budding researchers (called Na Liko Noelo in Hawaiian), of which 40
      (68%) have participated in at least one training and 28 (36%) have served as
      investigators, 40 (51%) as research assistants, and 10 (13%) as mentors on cancer
      prevention and control studies. The major challenge for Na Liko Noelo is finding
      the time needed to devote to research and writing scientific papers, as most have
      competing professional and personal obligations. Program evaluation efforts
      suggest, however, that 'Imi Hale and its Na Liko Noelo program are well accepted
      and are helping develop a cadre of community-sensitive indigenous Hawaiian
      researchers.

PMID- 16281706
TI  - Addressing the cancer control needs of Pacific Islanders: experience of the
      Pacific Islander Cancer Control Network.
AB  - PURPOSE: This paper describes the accomplishments of the Pacific Islander Cancer
      Control Network (PICCN). PICCN's objectives fall under two broad categories:
      increasing cancer awareness and enhancing cancer control research among Samoans,
      Tongans, and Chamorros. METHODS: PICCN established an infrastructure for
      addressing the goals that include the University of California, Irvine; the UCI
      Chao Family Comprehensive Cancer Center; and community-based organizations (CBOs)
      in areas where large numbers of Pacific Islanders live. Activities that increase
      cancer awareness include assessing existing cancer education materials,
      developing new culturally-sensitive materials, and distributing the materials in
      a culturally-sensitive manner. Activities that enhance cancer control research
      include training Pacific Islander investigators and providing them with mentors
      to help with the development of research projects. RESULTS: During the four
      project years, PICCN has conducted more than 180 cancer awareness activities in
      its six study sites: Carson, CA; San Mateo, CA; San Diego, CA; Salt Lake City,
      UT; American Samoa; and Guam. PICCN members have also participated in conferences
      and lead discussions about the importance of clinical trials for Pacific
      Islanders. In addition, the Network has trained nine Pacific Islander
      investigators (three individuals from each ethnic group) in its cancer control
      academy. Finally, PICCN investigators are conducting pilot research projects that
      will answer important questions regarding the cancer control needs of these
      Pacific Islanders and set the stage for interventions aimed at addressing the
      needs. CONCLUSION: PICCN is advancing the national goal of eliminating cancer
      related health disparities through its cancer awareness and research activities
      for Pacific Islanders.

PMID- 16281707
TI  - APPEAL: fighting for social justice in tobacco control among Native Hawaiians and
      Pacific Islanders through leadership and capacity building.

PMID- 16281708
TI  - The Pacific Island Health Care Project: easing the cancer burden in the United
      States associated Pacific Islands.
AB  - Cancer is a serious and ever increasing problem in the United States Associated
      Pacific Islands (USAPIs). Nearly 30% of all consultations and referrals are for
      cancer. Depending on the type of cancer, the prognosis for long-term survival is
      often poor and the cost of caring for such patients is considerable. Tripler Army
      Medical Center (TAMC) provides tertiary medical care to patients from the USAPIs
      in support of Graduate Medical Education (GME) at no cost to the patient or
      jurisdiction. Continuing its tradition of leading telemedicine initiatives in the
      Pacific, TAMC has developed a web-based electronic consultation and referral
      network, the Pacific Island Health Care Project (PIHCP). Ten sites in Micronesia
      and one in American Samoa were provided with computer equipment. Local clinicians
      request consultation from TAMC specialists through the internet, attaching
      supporting imagery. The consults are posted on a secure web page, where they are
      viewed, evaluated, forwarded, and commented on by the consultants. Experience
      with more than 2,100 cases indicates that the Internet can be easily used as a
      store-and-forward consultation format and offers a cost effective means for
      distance consultation, referral, and learning. This format has provided for a
      more rational evaluation of all patients but especially patients with cancer.
      Patients who are terminally ill, have widely metastasized disease, and/or have
      inoperable tumors or recurrences are excluded so that limited resources can be
      used for those most likely to benefit. There has been overwhelming enthusiasm for
      such Internet consultations between referring physicians and consultants. Many
      Pacific Islander patients have received state-of-the-art medical care through
      this program. At the same time, the training of TAMC physicians and residents has
      been enhanced by their opportunity to care for these remarkable and deserving
      patients from the Pacific.

PMID- 16281709
TI  - National Cancer Institute's Cancer Information Service in the Pacific: developing
      partnerships to meet the cancer information needs of Asian American & Pacific
      Islander populations.

PMID- 16281710
TI  - The traditional Hawaiian diet: a review of the literature.
AB  - The prevalence of obesity is increasing among all Americans, including Native
      Hawaiians. Because obesity is a risk factor for major chronic diseases and
      shortens lifespan, it is important to develop and test interventions to prevent
      and reduce it. Traditional Hawaiian Diet (THD) programs, conducted over the last
      two decades, were examined in the context of national information on weight loss
      and obesity prevention programs. This review reveals that THD programs appeal to
      Native Hawaiians, especially the education about the health and cultural values
      of native foods and the support of peers. The majority of participants realize
      short-term weight loss and improvements in health, but few individuals sustain a
      significant weight loss. Most participants have difficulty adhering to the THD,
      citing barriers to accessing fresh, affordable produce and the lack of support
      systems and environments that embrace healthy eating. Any THD program offered in
      the future should address these barriers and engage participants for at least a
      year. This review includes a logic model that can be used to help program
      providers improve THD programs and increase the rigor of evaluation efforts.
      Additionally, public health professionals and Native Hawaiians should advocate
      for environmental changes that will support healthy lifestyles, for example:
      increase access by Native Hawaiians to the land and ocean; provide land for home,
      neighborhood and community gardening; support local farmers; remove junk-food
      vending machines from public buildings (including schools); improve school
      lunches; and mandate daily, enjoyable physical education classes in schools and
      after-school programs.

PMID- 16281711
TI  - Report on the National Conference on Tobacco or Health conference, 2003.

PMID- 16281712
TI  - 9th Biennial Symposium on Minorities, the Medically Underserved and Cancer, 2004:
      a conference report.

PMID- 16281713
TI  - An outpouring of intellect and aloha: conference report on Kamehameha Schools'
      2003 Research Conference on the Education and Well-being of Hawaiians.

PMID- 16281714
TI  - [Prevention of periprocedural myocardial damage in patients undergoing
      percutaneous coronary intervention].
AB  - Myocardial injury during coronary intervention occurs in 10-40% of cases and is
      often characterized by a slight increase in the markers of myocardial necrosis,
      without symptoms, electrocardiographic changes or impairment of cardiac function.
      However, even small increases in creatine kinase (CK)-MB levels are an expression
      of a true and detectable infarction and may be associated with a higher follow-up
      mortality. The cause of CK-MB elevation in case of procedural complications is
      obvious; however, most cases of minor CK-MB elevation occur in patients with
      uncomplicated procedures with excellent final angiographic results. It has been
      suggested that the main mechanism explaining the occurrence of myocardial
      necrosis during otherwise successful coronary intervention may be distal
      microembolization of plaque components, an enhanced inflammatory state or total
      plaque burden and/or instability. Different treatments have been proposed to
      prevent myocardial injury during coronary intervention, including nitrate
      infusion, intracoronary beta-blockers, adenosine and IIb/IIa inhibitors, but none
      of these (apart from the use of IIb/IIIa inhibitors) have been routinely
      introduced into clinical practice. Previous observational studies suggested a
      beneficial effect of pre-treatment with statins in this setting; the ARMYDA
      (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) trial is the
      first prospective, randomized, placebo-controlled study, evaluating the effects
      of 7-day therapy with 40 mg/day of atorvastatin on post-procedural release of
      markers of myocardial damage in patients with stable angina undergoing
      percutaneous intervention. In this study therapy with atorvastatin was associated
      with an 80% risk reduction in the occurrence of periprocedural myocardial
      infarction, as well as with a significant reduction in post-intervention peak
      levels of all markers of myocardial damage. The mechanisms underlying the
      beneficial effects of atorvastatin may be an inflammatory action reducing
      myocardial injury necrosis due to microembolization, an improvement in
      endothelial function on microcirculation, and direct myocardial protection.

PMID- 16281715
TI  - [Use of imaging in the evaluation of heart transplant recipients].
AB  - Common complications after heart transplantation include acute rejection and
      coronary allograft vasculopathy. In order to detect the presence of rejection,
      tissue Doppler imaging echocardiography provides high accuracy and allows to
      optimize the timing of endomyocardial biopsies, which remain the cornerstone in
      rejection diagnosis. Coronary allograft vasculopathy is often a diffuse disease
      so that it is difficult to recognize by imaging modalities, such as myocardial
      perfusion scintigraphy, which are based on intra-patient comparison of different
      areas. Quantitative assessment of the myocardial blood flow by positron emission
      tomography overcomes this issue. Dobutamine stress echocardiography provides
      accurate diagnosis as well as useful prognostic information. Nevertheless,
      intracoronary ultrasound is nowadays considered the gold standard for
      vasculopathy assessment, since it is able to detect a minimum intimal thickening
      which represents the early feature of disease. Magnetic resonance represents the
      most attractive approach, though it has not yet gained widespread clinical use.

PMID- 16281716
TI  - [Breast arterial calcifications and coronary calcifications: a common link with
      atherosclerotic subclinical disease?].
AB  - Coronary artery calcifications seem to be correlated with a high risk of coronary
      heart disease. Computed tomography has been shown to be capable of providing
      accurate, non-invasive measurements of coronary artery calcifications. Coronary
      calcium is a recognized marker of atherosclerosis. Atherosclerotic burden of
      coronary arteries correlates strongly with the amount of coronary artery
      calcifications measured by computed tomography. The presence and extent of breast
      arterial calcifications detected at mammography has been associated with diabetes
      and hypertension and it seems to be correlated with the extent of coronary
      atherosclerosis. This review analyzes the relationship between coronary artery
      calcifications, breast arterial calcifications and the increased risk of
      subsequent cardiovascular events.

PMID- 16281717
TI  - [Cardiac arrest management in outpatient clinics: integration between hospital
      emergency care and the 118 emergency system in the model of Turin ASL 3].
AB  - The incidence of sudden cardiac death ranges from 0.4 to 1.28 every 1000
      inhabitants per year. Sudden cardiac death is responsible for about 10% of all
      deaths in Italy in 2000. It is unpredictable and is related to malignant
      ventricular arrhythmias that may be interrupted in more than 70% of cases.
      Survival rates generally do not exceed 5% in out-of-hospital cardiac arrest, but,
      as previously reported, early defibrillation may increase survival rate by 3
      times. The Italian law of April 3, 2001, and its recent amendments authorized
      healthcare providers and trained lay rescuers to use automated external
      defibrillators either for in-hospital or out-of-hospital settings. We planned a
      program for early defibrillation in ASL 3 in four outpatient clinics where a
      transit of 300,000 patients was expected in 2004. Defibrillators were placed in
      wall-mounted boxes. Opening of these boxes enable an automatic calling to the 118
      emergency service that is able to dispatch an advanced cardiac life support team
      to the pertinent outpatient clinic. The system of wall-mounted boxes
      automatically communicates by modem with a programmable rate, the state of repair
      and efficiency of the single boxes, in order to simplify the control of the whole
      system of defibrillators. This plan of Turin ASL 3 is innovative in the
      metropolitan area and emphasizes the central role of the 118 emergency system in
      the management of out-of-hospital cardiac arrest, even in hospital settings such
      as outpatient clinics with a high number of old users at higher risk of cardiac
      events. This plan with the availability of automatic calling of the 118 emergency
      service will be proposed to remaining local hospital utilities for their
      outpatient settings as well as to other public utilities such as general stores,
      drugstores, airports where a significant transit mat be expected. The plan will
      include a specific training for the use of automated external defibrillators by
      first responders.

PMID- 16281718
TI  - [Percutaneous coronary revascularization in patients over eighty: acute and long
      term results].
AB  - BACKGROUND: As a consequence of prolonged life expectancy the number of older
      patients with symptomatic coronary artery disease is constantly increasing. The
      aim of the study was to evaluate procedural success, immediate and long-term
      outcomes and the predictive factors of prognosis in patients aged > 80 years with
      high-risk coronary artery disease treated with coronary angioplasty. METHODS: In
      this retrospective study, we report the diagnostic and therapeutic strategies
      adopted in patients aged > 80 years admitted to our institution for acute
      coronary syndrome with or without ST-segment elevation or disabling angina (CCS
      class 3-4) and the immediate and long-term results of patients treated with
      coronary angioplasty. RESULTS: A conservative approach was adopted in 180
      patients (33%, group 1) out of the total number of 545 patients, while 365
      patients (67%, group 2) underwent coronary angiography. Among these, 85%
      underwent revascularization. Relevant comorbidities were significantly higher in
      group 1 (59 vs 16%, p < 0.001) while a clinical presentation with ST-elevation
      myocardial infarction was prevalent in group 2 (15 vs 6%, p = 0.007). The in
      hospital mortality was 19% in group 1 and 7.9% in group 2 (p = 0.001). Among 198
      patients treated with angioplasty, procedural success was achieved in 93% of
      cases, with 8% in-hospital mortality. Periprocedural myocardial infarction
      occurred in 3.3% and major bleeding in 5.6% of patients. At multivariate analysis
      ST-elevation myocardial infarction and cardiogenic shock were significantly
      related to the in-hospital mortality. At follow-up (mean 25 +/- 13 months) 13
      patients died, 9 from cardiac causes and 4 from noncardiac events. Recurrence of
      ischemia requiring revascularization occurred in 15.9% of cases. Cumulative
      survival at follow-up was respectively 86% at 1 year and 83% at 5 years, while
      the event-free survival at 5 years was 59% in the entire group, without any
      significant difference among patients with multivessel disease in whom a complete
      vs an incomplete revascularization was performed. The presence of severe
      comorbidities appeared to be the only predictive factor of unfavorable outcome at
      long-term follow-up at multivariate analysis. CONCLUSIONS: In patients aged > 80
      years with symptomatic ischemic heart disease at high risk, the invasive approach
      was prevalent. Higher mortality rates were found in patients in whom coronary
      angiography was not performed. Comorbidities represent an important negative
      prognostic factor, impairing both the possibility of an invasive approach and
      conditioning an unfavorable outcome of revascularized patients. Coronary
      angioplasty can be successfully performed even in elderly patients. The in
      hospital mortality turns out significantly higher in the setting of an acute ST
      elevation myocardial infarction or in cardiogenic shock patients. For patients
      overcoming the acute phase, high survival rates can be expected at follow-up.

PMID- 16281719
TI  - [Sirolimus-eluting stent for in-stent restenosis treatment: single center results
      in an unselected study population].
AB  - BACKGROUND: Sirolimus-eluting stents have already proved to be efficient in the
      prevention of restenosis in de novo lesions and have been already proposed as a
      potential treatment of in-stent restenosis. In the present study, we evaluated
      the effectiveness of sirolimus-eluting stent implantation in unselected patients
      with in-stent restenosis. METHODS: Fifty consecutive patients (59 lesions) were
      treated with sirolimus-eluting stents for instent restenosis. The incidence of
      major adverse cardiovascular events and restenosis was evaluated at 1-year
      clinical and angiographic follow-up. RESULTS: At baseline, 54% of the lesions
      were complex (46% proliferative and 8% total occlusions). Small vessel size (< or
      = 2.5 mm) was present in 30%, a long lesion (> 20 mm) in 25%, and diabetes in 42%
      of the patients. The angiographic follow-up was obtained in 47 patients (55
      lesions). Restenosis was observed in 13% of the lesions. At the 1-year follow-up,
      the incidence of major adverse cardiovascular events was 16% (4% acute myocardial
      infarction, 12% target lesion revascularization). CONCLUSIONS: This study
      confirms the efficacy of sirolimus-eluting stents for the treatment of instent
      restenosis in an unselected population of consecutive patients at high risk of
      restenosis and with a broad range of morphological lesion patterns.

PMID- 16281720
TI  - [Myocardial strain rate in normal subjects].
AB  - BACKGROUND: Strain rate (SR) is considered as an accurate index of myocardial
      contractility, capable of differentiating regional myocardial contractions from
      hypokinetic ones. It is not dependent on adjacent myocardial motion or heart
      translation. Clinical studies proved this method to be useful in case of heart
      disease but detailed analyses, homogeneous normal reference parameters, and
      studies about atrial myocardium are still scanty. The aim of this study was to
      evaluate longitudinal SR of the left myocardial ventricle and atrium in normal
      subjects. METHODS: Nineteen normal subjects were examined with tissue Doppler
      imaging; SR values were obtained off-line on images stored by internal software
      using the curved M-mode of the left ventricle and atrium. Mean SR values were
      obtained at the distal, mid, and basal left ventricular segments of the septum
      and lateral wall, and at the basal and distal left atrial segments of the septum
      and lateral wall. RESULTS: Ventricular SR values showed a negative systolic peak,
      two positive peaks at rapid filling and one at late filling. In the distal
      segments systolic SR values were lower and that of rapid filling were higher.
      Systolic events showed a progression from the base to the apex; the diastolic
      ones had an opposite trend. SR values of the closest atrial segments to the
      annulus showed the same progression as the ventricular ones; in the distal
      segments systolic SR was positive and diastolic SR was negative. The
      atrioventricular sequence of the cardiac cycle is identified. CONCLUSIONS: The
      method to obtain SR is semiautomatic and objective; image acquisition at a frame
      rate > 100/s identifies accurately the components of the SR curves. The analysis
      of the progression of events can allow to study ventricular and atrial
      synchronization of contraction, relaxation, and compliance.

PMID- 16281721
TI  - [Unruptured aneurysm of non-coronary sinus of Valsalva mimicking a right atrial
      mass].
AB  - Sinus of Valsalva aneurysms are extremely rare with a predominance in the Asian
      population. The clinical presentation may be ambiguous, depending on which sinus
      is affected and on the conditions of the lesion. We report a case of a 33-year
      old patient with Down syndrome. Ambulatory transthoracic and transesophageal
      echocardiography both show a mass located in the right atrium presumed to be of
      mixomatous nature. Intraoperative transesophageal echocardiography and surgical
      exploration lead to the diagnosis of sinus of Valsalva aneurysm.

PMID- 16281722
TI  - Demography and function of children with limb loss.
AB  - This retrospective study was designed for the period 1982-2002 to collect the
      basic data on the demography, level and side of the amputation, involved limbs,
      age, gender, and prosthetic functional level in children with limb loss. A total
      of 232 children were assessed through their prosthetic records. Seventy-two
      percent (195 children) presented lower-limb involvement, and 28% (77 children)
      had upper-limb loss. The age of the children varied between 1 and 15 years with a
      mean age of 9.90 +/- 2.32 years. Results of the study revealed that the leading
      amputation cause in children was congenital limb absence. The most frequent
      levels were determined as trans-tibial and trans-radial in lower and upper limbs,
      respectively. Findings showed that more boys (60%) were affected, and 84% of all
      amputations were found to be unilateral. It was also seen that right-side
      amputations (54%) were more common than left-side amputations (46%). The outcome
      of the study showed that 96% of children with lower-limb loss reached a
      functional gait pattern without any aids, while the percentage of independence in
      activities of daily living was found to be 88% in upper-limb loss.

PMID- 16281723
TI  - Transition from sitting to standing after trans-femoral amputation.
AB  - Standing up is an important and common daily activity. It is essential for
      independence and a prerequisite for walking. Many elderly and many subjects with
      impairments have problems with transition from sitting to standing. The aim of
      the present study was to determine whether there was any difference between the
      characteristics of standing up in trans-femoral amputees and healthy subjects.
      Five young trans-femoral amputees and five healthy subjects were included in the
      study. They were asked to stand up. The body motion was recorded using an
      Optotrak contactless optical system. The force and moment vectors exerted on the
      seat were recorded by a JR3 six-axis robot wrist sensor. The force under the feet
      was recorded by two AMTI force plates. The trans-femoral amputees were found to
      stand up more slowly than the healthy subjects. The angles of the hip, knee, and
      ankle joints on the amputated side were different from the angles on the healthy
      side or in the healthy subjects. There was also a great difference in loading
      between the healthy and the prosthetic foot. It can be concluded that there are
      differences in standing up between the trans-femoral amputees and the healthy
      subjects. These differences may indicate a reason for problems many elderly trans
      femoral amputees face when standing up.

PMID- 16281724
TI  - Socket versus bone-anchored trans-femoral prostheses: hip range of motion and
      sitting comfort.
AB  - This is the first study to report on hip range of motion (ROM) among active
      prosthesis users, when wearing and not wearing a trans-femoral socket prosthesis
      and to compare with individuals rehabilitated with an osseointegrated bone
      anchored prosthesis. In addition, discomfort when sitting with the prosthesis is
      reported in both groups. The study group all had a non-vascular amputation and
      were divided into those supplied with a socket prosthesis (S group) (n = 43, mean
      age 51 years, 74% men) or a bone-anchored prosthesis (OI group) (n = 20, mean age
      46 years, 75% men). Active hip ROM was measured with a goniometer, and self
      reported problems with discomfort when sitting were recorded. The hip motion
      decreased in all directions when wearing the socket prosthesis compared to
      without it (P < 0.001 for all directions), and 37% of the subjects had less than
      90 degrees of hip flexion when wearing their prosthesis. Discomfort when sitting
      was reported among 44% (n = 19) in the S group and was more common among
      individuals with less than 90 degrees of hip flexion motion (P= 0.025). In the OI
      group, no restriction in hip motion was measured with the prosthesis, and no
      subject had less than 90 degrees of flexion and 5% (n = 1) reported discomfort
      when sitting. This study shows that a trans-femoral prosthetic socket
      significantly reduces the ROM of the hip and that discomfort when sitting is
      common among individuals wearing such prostheses. Further, the study confirms
      that individuals using a bone-anchored prosthesis have no restricted hip motion
      with the prosthesis and report very few problems with discomfort when sitting.

PMID- 16281725
TI  - Sand-casting technique for trans-tibial prostheses.
AB  - A sand-casting technique for trans-tibial sockets was applied to 28 amputees, and
      the prosthetic fit observed through transparent check sockets. The results were
      better than historical reports of fittings with plaster of Paris casting by
      qualified prosthetists. The fit was consistently and evenly larger than the
      stump, but total contact could be achieved by applying three (two to five) stump
      socks. This would normally be considered on the high side of a good fit.

PMID- 16281726
TI  - Are Canadian prostheses used? A long-term experience.
AB  - The Canadian prosthesis is indicated for the more proximal levels of amputation
      of the lower limb (very short trans-femoral, hip disarticulation and
      hemipelvectomy cases); it is frequently rejected by many patients for different
      reasons (awkwardness, intolerance of the socket, excessive energy expenditure to
      ambulate among others). The objective was to analyse the use or rejection of
      Canadian prostheses (n = 23) after an 8-year follow-up study (range: 2 -16
      years). The sample consisted of 52% men and 48% women, and the average age at the
      time of amputation was 52.26 +/- 19.71 SD years (range: 1-74 years). The most
      frequent aetiology was malignant tumour (56.5%). Eight of the subjects continued
      to use the prosthesis through the entire study (34.7%). Gender, age, and
      aetiology were not significant determinants of use. The daily use was 12.5 h per
      day. The rejection of the Canadian prosthesis was after 20 months of use (range:
      2-48 months), and the main reasons were death (all tumour causes), intolerance to
      the socket, or difficulty in ambulation. In conclusion, many years after their
      discharge from rehabilitation services, more than one-third of the sample (34.7%)
      were wearers of the Canadian prosthesis.

PMID- 16281727
TI  - Trans-femoral amputee gait: socket-pelvis constraints and compensation
      strategies.
AB  - The paper deals with the identification of motor strategies adopted by trans
      femoral amputees to compensate for the constraints of hip motion induced by the
      interference of the socket with the pelvis and, particularly, with the ischial
      tuberosity. A group of 11 subjects with trans-femoral amputation, three of whom
      wore two different prostheses, giving a sample size of 14 cases, were studied by
      gait-analysis protocols: the present paper focuses on the pelvis-thigh kinematics
      at foot strike. The results showed that, at the prosthetic side, the hip is
      significantly less flexed and less extended, respectively, at the ipsilateral and
      contralateral foot strike. Moreover, the pelvis is significantly more anterior
      tilted at sound foot strike. The anterior step length showed a decreased sound
      limb anterior step in 12 out of 14 cases. The authors interpret these results as
      a combination of mechanical constraints and compensatory actions: the reduced
      prosthetic hip extension is determined by the mechanical constraint involved in
      the pelvis-socket interference; and the increased pelvis tilt and sound hip
      flexion occurring at the same time are compensating strategies, adopted by the
      amputees, in order to obtain a functional step length and symmetrical thigh
      inclinations. Those factors determine a gait pattern which is functional, only
      slightly slower than normal gait, and without any perceivable alterations. On the
      other hand, the authors show that the increased pelvis tilting necessarily
      overloads the lumbar tract of the spine and may be related to the frequent
      occurrence of low-back pain in amputee subjects, despite the positive functional
      gait recovery.

PMID- 16281728
TI  - Removable rigid dressings versus soft dressings: a randomized, controlled study
      with dysvascular, trans-tibial amputees.
AB  - This study compares a standard soft dressing (SSD) with a removable rigid
      dressing (RRD) in a randomized, controlled trial using 50 dysvascular trans
      tibial amputees. Both dressing types were applied immediately post-operatively
      and were only removed for wound dressing changes. Half the subjects were
      allocated prospectively by ballot to either the RRD group or the SSD group. There
      was a strong trend indicating that primary wound healing of the stump occurred
      almost 2 weeks earlier in subjects using the RRD (RRD = 51.2 days +/- 19.4; SSD =
      64.7 days +/- 29.5; P= 0.07; RRD: n =17; SSD: n = 14.) There were no significant
      differences between the other parameters measured which included time to
      prosthetic fitting, length of hospital stay, incidence of stump breakdown, and
      time taken for stump volume to stabilize. The incidence of stump damage due to
      falls was also recorded, the results indicating that RRDs may protect the new
      stump from trauma.

PMID- 16281729
TI  - Clinical, epidemiological and cost aspects of contact lens related infectious
      keratitis in Belgium: results of a seven-year retrospective study.
AB  - AIM: Evaluation of the clinical, epidemiological and cost aspects of contact lens
      related infectious corneal ulcers requiring hospitalisation. METHODS: A
      retrospective analysis was performed on the files of patients hospitalised for
      contact lens induced corneal ulcer in the eight Belgian University Hospitals over
      a seven-year period (January 1997 until December 2003). For all hospitalised
      patients registration of the diagnosis is compulsory using the International Code
      of Diagnostics (ICD-9). RESULTS: 107 patients with contact lens related corneal
      ulcer were included. The great majority, 99 subjects, used soft contact lenses,
      of which 9 were disposables, 73 planned replacement and 17 conventional lenses.
      Only 6 patients were night and day wearers. Three patients used daily disposable
      lenses. The most frequently cultured organisms were Pseudomonas and other Gram
      negative germs (70%) and Acanthamoeba (16%). The majority (77%) of the corneal
      ulcerations were localised centrally which resulted in an average visual loss of
      4 lines. In 16 patients a corneal graft was performed and one eye had to be
      eviscerated. CONCLUSION: Despite important technological improvements in contact
      lens materials and care systems, the problem of infectious ulceration has all but
      disappeared. On the contrary, during the study period, the number of patients
      hospitalised increased from 5 in 1997 to 22 in 2003, which is only partially
      explained by the increasing prevalence of lens wearers: 3,5% of the Belgian
      population in 1995 and 6,5% in 2003.

PMID- 16281730
TI  - [Bilateral optic neuropathy from methanol intoxication. A case report].
AB  - Methanol poisoning generally occurs after voluntary or accidental ingestion and
      can be responsible for blindness by optic neuropathy. We describe two cases of
      methanol poisoning who developed bilateral optic atrophy despite a treatment
      combining corticosteroids and vitamin B. Through these observations we recall the
      physiopathology as well as the clinical and therapeutic aspects of this type of
      intoxication.

PMID- 16281731
TI  - Trilateral retinoblastoma: a literature review, 1971-2004.
AB  - This study analyzes modern views on the history, variants, age at diagnosis of
      trilateral retinoblastoma, median time from retinoblastoma to trilateral
      retinoblastoma, the largest size and percentage of trilateral retinoblastoma
      among retinoblastoma cases, functions of pineal gland, genetics, ocular and
      intracranial histology, diagnosis, treatment, therapy results, survival rates and
      frequency of screening of trilateral retinoblastoma.

PMID- 16281732
TI  - [Amblyopia and strabismus in our environment].
AB  - PURPOSE: This study aimed to identify the characteristics of amblyopia in a group
      of strabismic patients in our environment in order to improve management.
      METHODS: A prospective study was carried out in the General Hospital, Douala,
      from July 1991 to July 2003. All strabismic patients had a complete
      ophthalmological examination including an oculomotor evaluation and skiascopy
      after cycloplegia. RESULTS: 330 patients were examined. The mean age at initial
      consultation was 13.97 years +/- 12.21. The prevalence of amblyopia was 80.46% in
      esotropia and 59.40% in exotropia. The precocity of strabismus, eccentric
      fixation, torticollis, presence of a vertical element and nystagmus were
      aggravating factors for amblyopia. CONCLUSION: In order to carry out early and
      coherent management of strabismus, it is important to train and inform all those
      who are involved in the care process.

PMID- 16281733
TI  - Surgical treatment outcomes of congenital and juvenile cataracts.
AB  - PURPOSE: Evaluation of visual outcome after lens aspiration with or without
      intraocular lens implantation for isolated congenital and juvenile cataract in
      children aged 6 years and younger. MATERIAL AND METHODS: Retrospective review of
      48 children with isolated congenital and juvenile cataract who were surgically
      treated between January 1993 and December 2002 and had a minimal follow-up of 12
      months. RESULTS: In the group of children with unilateral cataract, 33% (3 out of
      9 children) of aphakic children and 45.5% (5 out of 11 children) of pseudophakic
      children attained a final best corrected visual acuity of 20/200 and 20/60
      respectively. In the group of children with bilateral involvement, 35% (6 out of
      17 children) of aphakic children have a final best corrected visual acuity of
      20/30 and 63.7% (7 out of 11 children) of pseudophakic children have a final best
      corrected visual acuity of 20/25 or more. CONCLUSION: The results of this study
      emphasize the need for early surgery and good organisation of postsurgical care
      in patients with pediatric cataract to optimise visual outcome. Furthermore
      patients with isolated unilateral congenital cataract surgically treated at an
      average age of 15 months without primary lens implantation and with variable and
      low compliance have suboptimal results. The effect of early surgery with primary
      lens implantation on the long term visual outcome in pediatric cataract needs to
      be further evaluated.

PMID- 16281734
TI  - Needling-revision of failed filtering blebs.
AB  - PURPOSE: To investigate the efficacy and safety of needling-revision of failed
      blebs after trabeculectomy. METHODS: A retrospective chart review of 28 eyes of
      28 patients who underwent a trabeculectomy with subsequent needling-revision
      between January 2002 and December 2003. The mean follow-up was 15 months after
      the first needling-revision. All interventions were conducted by the same
      surgeon. Absolute success was defined as an IOP <18 mmHg without medication or as
      an IOP reduction > 20% without medication if the preoperative IOP was < or = 21
      mmHg. Relative success was defined as meeting these criteria with or without
      medication. RESULTS: The mean interval between trabeculectomy and the first
      needling-revision was 5 months. Repeated needling-revision (up to 3 times) was
      performed as clinically necessary. In 90% of the needling-revisions 5-FU was used
      to prevent postoperative fibrosis. The mean +/- SD IOP before needling-revision
      and at the last follow-up was respectively 24.7 +/- 6 and 15.7 +/- 3 mmHg
      (p<0.001) Needling-revision was an absolute success in 39% (11/28) and a relative
      success in 68% (19/28). Minor complications attributed to needling-revision
      occurred in 32% including self reabsorbing subconjunctival bleeding (1),
      filamental (1) and punctate keratitis (1), transient choroidal effusion (3),
      wound leak (4) and hyphaema (2). Progression of cataract occurred in 1 patient. A
      serious complication occurred in 1 case (hypotony with persistent macular
      oedema). CONCLUSIONS: Bleb needling-revision can prevent more invasive
      intervention in a significant number of patients with failed trabeculectomy
      blebs. Complications are similar to those seen after trabeculectomy.

PMID- 16281735
TI  - One year of intravitreal injections of steroids.
AB  - PURPOSE: Chronic macular oedema sometimes does not respond to classic treatment
      such as laserphotocoagulation, periocular and systemic steroids or carbonic
      anhydrase inhibitors. High dose intravitreal injection of steroids can be a
      valuable alternative in these patients. METHODS: Sixty-four eyes of 51 patients
      with chronic macular oedema, refractory to conventional treatments, received an
      intravitreal injection of 4 mg Kenacort (triamcinolone acetonide). At
      postoperative controls (1 day, 1 month, 3 months, 6 months, 1 year), the visual
      acuity, intraocular pressure, central retinal thickness on OCT II were analyzed
      retrospectively. RESULTS: In the diabetic group, but also in cases of chronic
      uveitis, retinal vein thrombosis, birdshot chorioretinopathy, Irvine Gass
      syndrome, cellophane maculopathy and age-related macular degeneration with
      classic subfoveolar neovascular membrane, dramatic decrease of the oedema was
      observed on funduscopy and OCT. A statistically significant reduction of mean
      central foveal thickness of 61% at 1 week and 49% at 3 months post-injection was
      demonstrated on OCT. Considerable gain in visual acuity was noted. The highest
      benefit in post-operative visual acuity was achieved after 3 months and averaged
      a gain of +3.55 Snellen lines (n=39). In 17% of eyes a rise in intraocular
      pressure was noted. Unfortunately we had one case of endophthalmitis in a poorly
      regulated diabetic woman. Six eyes were retreated because of recurrence of
      macular oedema. CONCLUSION: Intravitreal injection of steroids can dramatically
      help in some cases of chronic macular oedema, not reacting to classic treatment.
      The injection should be performed under sterile conditions since endophthalmitis
      is a potential risk. The most frequent complication seems to be a rise in
      intraocular pressure in cortisone responders.

PMID- 16281736
TI  - Gaussian broad-beam excimer laser: clinical and experimental results.
AB  - PURPOSE: To evaluate the mid-term (1-3 years) results of the Gaussian broad-beam
      excimer laser Delivery System (DS) after single treatment for the correction of
      myopia. To study the corneal surface with scanning electron microscopy (SEM)
      after excimer laser ablation using a flying spot delivery system (Bausch & Lomb)
      and a Gaussian Delivery System (GDS) (InPro). METHODS: The 1035 consecutive eyes
      studied were split in four groups with respect to the treated myopia, expressed
      in spherical equivalent: low myopia up to -3.00 D (183 eyes), moderate myopia
      from -3.25 D to -6.00 D (540 eyes), high myopia from -6.25 D to -10.00 D (210
      eyes) and very high myopia from -10.25 D to -20.00 D (102 eyes). Four post-mortem
      eyes of two donors were treated using the flying spot DS on one eye and the GDS
      on the other eye. RESULTS: We achieved postoperative spheriqual equivalent within
      +/- 1 D of emmetropia in respectively 99.1%, 98.9%, 83% and 21% of the eyes of
      group 1, 2, 3 and 4. UCVA was 10/10 or better in respectively 65%, 51% and 19% of
      group 1, 2 and 3. UCVA was 5/10 or better in respectively 86% and 75% of group 3
      and 4. The defocus equivalent refraction was 1.0 or less in respectively 98%,
      93%, 62%, and 7% of the four groups. On SEM, the corneal surface presented a
      smooth and polished profile for the GDS. CONCLUSIONS: The Gaussian Delivery
      System gives comparable results to the flying spot laser system for surface laser
      ablation in myopic eyes up to -10 D. Advantages of this system are: smooth
      ablation surface, short treatment time, low haze rate, high reliability and easy
      maintenance of the device due to the optical DS. It is an interesting alternative
      for the more complex mechanical DS.

PMID- 16281738
TI  - The G protein-coupled receptors: pharmacogenetics and disease.
AB  - Genetic variation in G-protein coupled receptors (GPCRs) is associated with a
      wide spectrum of disease phenotypes and predispositions that are of special
      significance because they are the targets of therapeutic agents. Each variant
      provides an opportunity to understand receptor function that complements a
      plethora of available in vitro data elucidating the pharmacology of the GPCRs.
      For example, discrete portions of the proximal tail of the dopamine D1 receptor
      have been discovered, in vitro, that may be involved in desensitization,
      recycling and trafficking. Similar in vitro strategies have been used to
      elucidate naturally occurring GPCR mutations. Inactive, over-active or
      constitutively active receptors have been identified by changes in ligand
      binding, G-protein coupling, receptor desensitization and receptor recycling.
      Selected examples reviewed include those disorders resulting from mutations in
      rhodopsin, thyrotropin, luteinizing hormone, vasopressin and angiotensin
      receptors. By comparison, the recurrent pharmacogenetic variants are more likely
      to result in an altered predisposition to complex disease in the population.
      These common variants may affect receptor sequence without intrinsic phenotype
      change or spontaneous induction of disease and yet result in significant
      alteration in drug efficacy. These pharmacogenetic phenomena will be reviewed
      with respect to a limited sampling of GPCR systems including the
      orexin/hypocretin system, the beta2 adrenergic receptors, the cysteinyl
      leukotriene receptors and the calcium-sensing receptor. These developments will
      be discussed with respect to strategies for drug discovery that take into account
      the potential for the development of drugs targeted at mutated and wild-type
      proteins.

PMID- 16281737
TI  - New biochemical insights into the pathogenesis of osteoarthritis and the role of
      laboratory investigations in clinical assessment.
AB  - Osteoarthritis (OA) is among the most frequent diseases in the population and a
      common cause of pain and disability in adults. The principal disease hallmarks
      for assessment of OA are still clinical observation and radiographic aspects.
      However, the efficacy of therapeutic interventions is complicated by the time
      required to observe radiographic signs, useful for both diagnosis and assessment.
      Thus, laboratory markers have received growing attention in recent years, in an
      attempt to improve diagnosis, assessment of disease activity and severity, and
      evaluation of therapeutic effects. Many biomarkers have been proposed, in
      particular those reflecting cartilage and bone turnover and synovitis. Among
      these, COMP, antigenic keratan sulphate, hyaluronan, YKL-40, type III collagen N
      propeptide, and urinary glucosyl-galactosyl pyridinoline appear to be the most
      promising. However, serum or urinary determinations of these molecules are
      difficult to interpret adequately due to their complex metabolism. New
      ultrasensitive methods for C-reactive protein have improved the usefulness of
      this marker, especially in the assessment of disease activity. Routine
      examination of synovial fluid is still essential for diagnosis and includes
      leukocyte count and crystal detection; specialized testing includes the
      evaluation of the levels of markers of local inflammation such as
      metalloproteinases and cytokines, which appear to be crucial to the pathogenesis
      of OA.

PMID- 16281739
TI  - [Herbal medicines in Spain: the current situation].

PMID- 16281740
TI  - [Assessing preoperative use of medicinal plants during preanesthetic interviews].
AB  - OBJECTIVES: To assess the use of medicinal plant preparations in preanesthetic
      interviews at a Spanish university hospital. MATERIALS AND METHODS: A total of
      500 questionnaires were randomly distributed over a period of 3 months to
      patients attending a preanesthetic assessment interview. RESULTS: Of the 431
      valid questionnaires returned, 154 (35.73%) were from patients who reported
      consumption of some type of herbal remedy and 55 (12.76%) were from patients who
      used a medicinal plant considered in the literature to be potentially toxic.
      Consumption was higher among women (64.28%) (P < 0.001). Among users of these
      plants, 137 (88.96%) reported that they did not consider them to be medications
      and 141 (91.55%) would not have told the anesthesiologist about their use during
      a routine clinical interview. CONCLUSION: There is considerable use of medicinal
      herbs with potentially adverse interactions with various drugs used during the
      perioperative period. Anesthesiologists need to be familiar with such herbs and
      their effects and to ask specific questions about their use during the
      preanesthetic interview.

PMID- 16281741
TI  - [Comparison of the bispectral index and spectral entropy in gynecological
      surgery].
AB  - OBJECTIVES: Spectral entropy quantifies variations in cortical electrical
      activity measured by electroencephalography and frontal activity measured by
      electromyography. The aim of this study, in the context of general anesthesia,
      was to compare bispectral index values with the two components of spectral
      entropy: state entropy and response entropy. MATERIAL AND METHODS: Sixteen women
      (ASA I-II) undergoing gynecological surgery were enrolled. The bispectral index
      was maintained between 40 and 50 for all patients. Both sensors, for monitoring
      the bispectral index and spectral entropy, were placed on each patient.
      Simultaneous readings were recorded at the following moments: operating room
      arrival, induction, relaxation, intubation, switching on the vaporizer, start of
      surgery, traction of the intestinal mesenteries and maneuvering of the electric
      scalpel, switching off the vaporizer, end of surgery, during cough, extubation,
      and eye opening. The data sets were subjected to analysis of variance, and the
      intraclass correlation coefficient (ICC) was used to analyze agreement. RESULTS:
      Differences between mean values of the bispectral index, state entropy and
      response entropy were observed at operating room arrival, intubation, and
      induction. Differences when the patient awakened from anesthesia were observed
      only between the bispectral index and response entropy, on the one hand, and
      state entropy on the other. There was no agreement (ICC<0.7) upon operating room
      arrival, maneuvering the electric scalpel, or awakening from anesthesia.
      CONCLUSION: The bispectral index, state entropy, and response entropy show good
      agreement during recordings that reflect the effects of anesthesia. The
      differences observed at baseline and upon awakening can be attributed to frontal
      electromyographic activity. Distinguishing cortical electrical activity from
      frontal electromyographic activity may provide additional information in these
      situations.

PMID- 16281742
TI  - [Percutaneous tracheotomy with the Ciaglia Blue Rhino technique: a critical
      analysis after 1 year].
AB  - OBJECTIVES: To report our experience during a learning period with the Ciaglia
      Blue Rhino (William Cook Europe) kit for percutaneous tracheotomy. PATIENTS AND
      METHODS: This prospective, observational study included 38 adult patients who
      underwent elective placement of a percutaneous tracheostomy tube with the Ciaglia
      Blue Rhino introducer kit. The study was carried out from April 2002 to May 2003.
      The main variables analyzed were duration of the procedure, level of difficulty
      (easy, moderately difficult, difficult), and complications while the procedure
      was being performed. RESULTS: The mean time of orotracheal intubation was 13.5
      days (range, 2-28 days). The mean duration of the procedure was 12 minutes 36
      seconds (range, 4 minutes 30 seconds-29 minutes; 95% confidence interval, 10
      minutes 30 seconds-14 minutes 36 seconds). The procedure was rated easy in 60.5%
      of the cases, moderately difficult in 31.6%, and difficult in 7.9%. Some form of
      complication occurred in 28 patients (73.6%), the most common being puncture of
      the orotracheal tube (28.9%) and slight bleeding (26.3%). Two patients (5.2%)
      died, from massive hemorrhage in 1 case and pneumothorax in the other.
      CONCLUSIONS: The Ciaglia Blue Rhino technique for percutaneous tracheotomy is
      useful, rapid, and easy but not free of risk. There is a learning curve that
      calls for caution and an experienced physician to perform the maneuvers, given
      that potentially fatal complications can occur.

PMID- 16281743
TI  - [Cardiovascular and respiratory complications after pneumonectomy].
AB  - Thoracic surgery has made important progress thanks to parallel advances in
      anesthetic techniques, which have lowered mortality and complication rates.
      Pneumonectomy, however, continues to carry a high risk of perioperative death and
      morbidity, with complications involving the heart and lung being the most common.
      Pneumonectomy requires careful preoperative assessment to identify patients at
      high risk of cardiac complications. However, there is no evidence available on
      the best approach to take in determining risk of impaired lung function after
      pneumonectomy. Postoperative arrhythmias increase mortality, although evidence
      does not suggest a need for systematic prophylactic treatment of patients who
      will undergo lung resection. The incidence of acute myocardial infarction ranges
      from 1.5% to 5% and diagnosis is difficult because most episodes are silent. The
      incidence of post-pneumonectomy pulmonary edema is between 4% and 7% and evidence
      indicates that prevention is the most important therapeutic measure. Patients
      tend to have greater risk of pneumonia after thoracotomy, but few studies have
      provided a high level of evidence for the usefulness of antibiotic prophylaxis in
      chest surgery. The aim of the present study was to review the literature on the
      most common complications of surgery on the lung in order to support decision
      making based on the integration of knowledge and clinical judgment acquired with
      experience. A MEDLINE search was carried out to locate studies published from
      1980 through January 2005.

PMID- 16281744
TI  - [Severe hemodynamic deterioration during epidural anesthesia for endovascular
      treatment of thoracic aortic stenosis].
AB  - A 72-year-old woman diagnosed with critical descending aortic stenosis was
      scheduled for endovascular treatment by angioplasty and implantation of an aortic
      stent. Her medical history included arterial hypertension, lipid metabolic
      disorder, obesity, Takayasu disease, dermatopolymyositis, and alleged allergy to
      iodine contrast and local anesthetics. After the allergies were ruled out, it was
      decided to use a regional anesthetic technique to avoid the postoperative
      complications of general anesthesia and achieve better hemodynamic control during
      surgery. Surgery was carried out under epidural anesthesia and intravenous
      sedation. After angioplasty and during self-expansion of the stent, the patient's
      hemodynamics deteriorated rapidly; she lost consciousness and required
      orotracheal intubation and immediate resuscitation measures. The literature
      describes in detail the management of patients with thoracic aortic lesions,
      including the most appropriate way to provide anesthesia. General anesthesia
      seems to be preferred, although care is taken to individualize the decision. We
      analyze this case of a patient with severe thoracic aortic stenosis undergoing
      endovascular treatment under epidural anesthesia.

PMID- 16281745
TI  - [Hypovolemic shock during surgery caused by a rectus sheath hematoma].
AB  - Prophylactic treatment with low molecular weight heparins (LMWH) is currently
      widely used to prevent thromboembolic events. However, such treatment is not free
      of risk. Among the possible complications described is rectus sheath hematoma. We
      report the case of a patient undergoing surgery for a hypophysial adenoma
      approached by the transsphenoidal route. He received LMWH prophylaxis for
      thromboembolism and showed a tendency to hypotension during surgery. The
      patient's condition deteriorated to hypovolemic shock accompanied by episodes of
      atrial fibrillation with rapid ventricular response. With the transfusion of
      medications, blood products and plasma volume expanders, the patient was
      stabilized and surgery was completed. A computed tomography scan then revealed a
      hematoma occupying the greater part of the left anterior rectus muscle. With
      conservative wait-and-see treatment the abdominal symptoms disappeared and the
      hematoma gradually receded until fully resolved. Spontaneous rectus sheath
      hematoma is a rare condition. Presentation is quite nonspecific and computed
      tomography is needed for reaching a firm diagnosis. When a hematoma is large, the
      initial clinical picture may include hypovolemic shock, which may develop during
      surgery if the hematoma is not diagnosed early. Intraoperative management will be
      much more difficult than it would have been if diagnosis and treatment had taken
      place before the operation.

PMID- 16281746
TI  - [Anesthetic management for thoracoscopic repair of type I esophageal atresia with
      continuous-flow single-lung ventilation].
AB  - We describe a continuous flow mode of ventilation for repair of type I esophageal
      atresia in an infant. This type of atresia is defined by distal stenosis of the
      esophagus with a proximal blind pouch and no connection to the tracheobronchial
      tree. In traditional repair procedures the surgical approach is by thoracotomy,
      but newer videoassisted thoracoscopic techniques have introduced novel challenges
      to ventilatory mechanics in these low-weight infants. The literature contains
      little discussion of the anesthetic management or respiratory mechanics of these
      patients. Trying to maintain adequate tidal volume and oxygenation while
      thoracoscopic maneuvers take place increases the risk of barotrauma. Single-lung
      ventilation with a continuous flow respirator was effective in the case we
      report.

PMID- 16281747
TI  - [On the information patients receive].

PMID- 16281748
TI  - [Emergency lower limb anesthesia by combined sciatic-femoral nerve block].

PMID- 16281749
TI  - [Epidural anesthesia and analgesia in a patient with cerebral manifestations of
      Wilson's disease].

PMID- 16281750
TI  - [Attempted suicide with super warfarin].

PMID- 16281751
TI  - [Delayed improvement of anemia treated with intravenous iron and epoetin alfa
      after hip replacement surgery].

PMID- 16281752
TI  - [Selective intubation through a rigid bronchoscope].

PMID- 16281753
TI  - [Usefulness of scales for predicting postoperative nausea and vomiting].

PMID- 16281754
TI  - [Randomized controlled trial comparing a low dose to a conventional dose of
      hyperbaric bupivacaine for scheduled cesarean section. Reflections].

PMID- 16281756
TI  - [The incorporation of hospitals--the need and the significance].

PMID- 16281755
TI  - [Distal end of a weighted nasogastric tube in the right bronchial tree].

PMID- 16281757
TI  - [Food allergy--effect of physician attitude on the diagnosis and reported
      prevalence].
AB  - BACKGROUND: There is great variation in the reported incidence of food allergies,
      especially the estimated cross allergy to cow's milk and soy. OBJECTIVE: To
      assess the attitude of allergists, pediatric gastroenterologists, chief
      pediatricians and physicians working in the community to cross-sensitivity to
      cow's milk and soybean. Sesame allergy was used to assess the physician's
      familiarity with food allergy. METHODS: Questionnaires were mailed to 186
      physicians of different disciplines. The opinions of primary physicians in the
      community were assessed according to 171 questionnaires completed at a food
      allergy conference. RESULTS: A total of 54% of the allergists estimated that less
      than 5% of children with cow's milk allergy are allergic to soy, significantly
      lower than pediatric gastroenterologists and community physicians. On the other
      hand, only 15% of the pediatric gastroenterologists reported that they
      encountered patients allergic to sesame, significantly less than allergists (65%)
      and chief pediatricians (44%). Only half (51%) of the allergists encountered
      patients allergic to both cow's milk and soy, significantly less than pediatric
      gastroenterologists (88%) and chief pediatricians (80%). Although the community
      physicians felt that the incidence of cross-sensitivity to cow's milk and soy was
      high, 94% of them were familiar with only a few such patients. CONCLUSIONS: There
      is significant variability in the attitude and judgment of physicians from
      different specialties regarding food allergy. It seems that the physician's
      opinion is influenced by "general knowledge" more than by his own experience. We
      suggest emphasizing through education that there are two distinct entities of
      cow's milk intolerance: IgE-mediated allergy and non-IgE-mediated.

PMID- 16281758
TI  - [Incidence of influenza among patients admitted to the department of internal
      medicine during the winter season].
AB  - BACKGROUND: Influenza is a common disease, especially in the winter season.
      Influenza virus causes symptoms of acute viral illness, development of
      complications and worsening of chronic diseases. Vaccination may prevent
      influenza illness. OBJECTIVES: 1. To determine the rate of vaccination against
      influenza. Furthermore, in the immunized patients--the study aimed to determine
      the efficiency of the vaccination. 2. To determine the incidence of influenza
      illness among patients admitted to a Department of Internal Medicine during the
      winter season. METHODS: We performed a prospective screening of 124 consecutive
      patients hospitalized in the Department of Internal Medicine during February
      1998. Demographic parameters (age, sex) and admission diagnosis were collected.
      All patients were asked about influenza vaccination in the last fall. Blood
      samples were collected on admission and 10-30 days later. Three relevant virus
      subtypes were examined. Virus subtype was determined in all patients with
      evidence of influenza illness. RESULTS: Eleven patients (8.9%) were found with
      evidence of acute influenza illness at the time of hospitalization. The rate of
      patients with chronic pulmonary disease was higher in this group than in the
      group without evidence of influenza (p = 0.03). Forty-four out of 124 patients
      (35.5%) had been vaccinated against influenza. In the vaccinated patients, the
      protective antibody level for all 3 subtypes developed in 27.3% of cases and for
      one or two subtypes in 50% of cases. In 22.7% of patients no protective level of
      antibody was detected for any subtype. CONCLUSIONS: It is necessary to encourage
      vaccination in the high-risk group patient, especially those with chronic
      pulmonary disease. It is essential to develop new vaccination strategies and
      prophylactic antiviral medications.

PMID- 16281759
TI  - [Annual rate of development of noise induced hearing loss in exposed workers].
AB  - The rate of development of noise induced hearing loss (NIHL) in a group of 150
      male workers exposed to industrial noise of over 85 dBA, was compared with the
      rate of a group of 40 unexposed workers. It was found that while the average
      annual rate of decline in the exposed group (for frequencies 1000-4000 HZ) was
      about 1 dB/year, it was less than 0.5 dB/ year in the unexposed group. These
      findings attest to the need to improve current prevention modalities (hearing
      conservation programs). In addition, the findings point to the importance of
      guaranteeing the accuracy of the audiometric tests as the usual "measurement
      error" is often greater than the expected real change (1-2 dB/year). These
      findings also question the value of current annual audiometry (a statutory
      requirement) in relation to providing significant new information.

PMID- 16281760
TI  - [Legal involvement in psychiatric care].
AB  - In an amendment to the law regarding the treatment of the Mental Health patient
      in 1991, authority was given to the regional psychiatrists' committee to oversee
      compulsory orders for psychiatric hospitalization and compulsory orders for
      outpatient psychiatric treatment--and the extension of these orders. On 1st of
      June 2002 a pilot study was started in the Jerusalem region, in which mental
      health patients were to be represented by lawyers employed by the Ministry of
      Justice. The pilot study began as an initiative of the Ministry of Justice, in
      agreement with the Ministry of Health. We describe 3 cases which demonstrate that
      the procedure of legal representation lacks the necessary balance between medical
      and legal considerations. The decision of the regional psychiatrists' committee
      or the court is liable to worsen the patients' mental health status and even to
      accelerate aggression towards self or others. In rare cases a premature discharge
      based on legal considerations rather than medical evaluation may result in
      suicide, as demonstrated in one of the vignettes. The article discusses the
      unbalanced approach of legal versus medical consideration, preference of
      "liberty" over health and the "wish" of the patient rather than his well-being.
      The article considers the unbalanced approach of the legal system to appeals of
      therapists against the decision of the regional psychiatrists' committee, where
      prosecutors of the state decided an appeal of this kind over the staff treating
      the patient has no precedence. That was presented as justification that it should
      be rejected. A pilot study compared between patients discharged from compulsory
      hospitalization through regional psychiatrists' committee or court and patients
      discharged on a medical basis without legal interference. The study showed a
      shorter stay in the community in the first group (42%) compared to 75% stay in
      the community in the second group, after six months. We are of the opinion that
      the current provision of legal assistance is lacking the necessary balance
      between medical and legal considerations; the 'wish for freedom' as a default,
      although illogical, is within the new system of legal aid, and is more
      considerate and important than the 'best interests' of the patient and his
      health.

PMID- 16281761
TI  - [Emergency room consultation policy prevents surgery delay in elderly patients
      with hip fractures].
AB  - Clinical guidelines for the management of hip fractures strongly emphasize the
      critical role of early surgery as a major factor affecting better health
      outcomes. Shortening the time from admission to pre-operative consultation by
      bringing the consultants to the emergency room, before patient admission to the
      orthopedic ward, is am efficient cost effective hospital policy that enables
      adherence to guideline recommendations. Early pre-operative specialist
      consultation is an efficient cost effective policy for preventing delay of
      surgery following hip fracture in the elderly.

PMID- 16281762
TI  - [Coronary artery imaging using computed tomography (CT): present and future].

PMID- 16281763
TI  - [Coronary artery imaging using cardiac CTA].
AB  - For many years noninvasive imaging of the coronary arteries was limited due to
      cardiac motion and the tortuous course of the arteries through the imaging plane.
      The introduction of new 16 and 64 detectors (multi-slice) CT scanners allows
      noninvasive imaging of the coronary arteries as well as the heart and great
      vessels. Soft atheromatous plaques can be evaluated and arterial stenosis grading
      is now feasible by "freezing" the heart motion, using ECG gated retrospective
      reconstructions. In addition, this novel technique can provide data about cardiac
      function, including heart muscle contractility, perfusion and ejection fraction.
      The cardiac CTA study, performed during one breath-hold, involves the intravenous
      injection of non-ionic iodinated contrast medium, and the use of ionizing
      radiation. Cardiac CT angiography is highly sensitive in the diagnosis of
      arterial luminal narrowing and stenosis, patency of intravascular stents and is
      useful in the follow-up of CABG bypass surgery. In addition, it will probably
      play an important role in evaluating high risk asymptomatic people, as well as
      patients with unclear cardiac symptoms.

PMID- 16281764
TI  - [Pharmacogenetics: towards personalized medicine].
AB  - For 50 years, pharmacogenetics has been studying the genetic basis for
      variability in drug response between individual patients, both with respect to
      drug toxicity and drug efficacy. Following the completion of The Human Genome
      Project about three years ago, and the development of technologies allowing rapid
      identification of polymorphic alleles using DNA chips, pharmacogenetics would
      soon allow the introduction of personalized medicine. For most medical
      disciplines, this would allow pharmacotherapy according to each patient's
      individual genetic data. This would allow a reduction in the rates of adverse
      drug reactions, currently responsible by American and European estimates for
      about 6% of new admissions to internal medicine wards, and causing more morbidity
      annually than road accidents or breast cancer. The purpose of this review is to
      delineate the principles of pharmacogenetics, focusing on the aspects closest to
      implementation in the clinic: the polymorphism of liver CYP450 metabolic enzymes,
      mostly CYP2D6 and CYP2C19. We shall also review current efforts to better
      understand the scope of human genome diversity, and present several examples for
      variability in drug efficacy and genetic polymorphism of drug target genes.
      Education of health professionals in pharmacogenetics as part of their
      pharmacology curricula, and explaining its potential to the general public, would
      be indispensable for the success of personalized medicine.

PMID- 16281765
TI  - [Exercise prescription for diabetics: more than a general recommendation].
AB  - Physical activity (PA) offers numerous benefits in diabetes prevention and
      management. These include better glycemic control, reduction of co-morbidities
      such as hypertension, dyslipidemia and cardiovascular disease, decreased
      mortality and improved quality of life. Many caretakers are unaware of the
      specific recommendations and restrictions regarding PA in diabetic patients. This
      may result in the withholding of an important therapeutic tool from patients, the
      unnecessary limitation of PA in patients keen to undertake it, or, on the other
      hand, in adverse reactions to exercise which may be prevented. This review
      presents PA recommendations in both type 1 and 2 diabetics, which include aerobic
      activity and strength training. Several safety points before commencing or
      increasing the intensity of a PA program are also addressed; assessment of the
      cardiovascular response to exercise, the presence of retinopathy, neuropathy,
      nephropathy, and proper foot care, are essential.

PMID- 16281766
TI  - [A review of the evidence based smoking cessation interventions delivered by the
      family physician].
AB  - Smoking is one of the most preventable causes of morbidity and mortality
      resulting in almost 10,000 deaths each year in Israel. Since tobacco-related
      disease is preventable, efforts to promote cessation in patients who smoke should
      be a routine step in preventive primary care measures. In Israel, 26% of the
      adult population smoke. Within this group, a third want to quit but only two
      percent succeed in abstaining from smoking for a whole year. Family physicians
      are in an ideal position to facilitate patients' attempts to quit smoking: 70% of
      smoking patients report that firm, supportive messages from their family
      physician can act as an important motivating factor to quit smoking. The updated
      Clinical Practice Guidelines from the US Public Health Service recommend that
      family physicians should opportunistically advise smokers to stop smoking during
      routine consultation, encourage and assist smokers in the use of nicotine
      replacement therapies or bupropion and refer smokers to professional behavioral
      or psychological counselors specializing in smoking cessation. Most physicians
      rank smoking as the most important behavior affecting health, but few physicians
      are confident in their own ability to help their patients stop smoking. In this
      review the authors present several evidence-based strategies that were found to
      be helpful in promoting smoking cessation when delivered by general
      practitioners. The power of the physician's advice, first and second line agents,
      behavioral counseling and stage based interventions, are all discussed in detail.

PMID- 16281767
TI  - [Political poisoning with dioxins--a weapon of chemical "disgracefulness"].
AB  - The recent attempt to poison Ukrainian President, Viktor Yuschenko with dioxins,
      raised public concern regarding this toxic chemical. In industrial countries,
      there is a constitutive exposure of humans to dioxin compounds, which are formed
      as by-products in manufacturing processes of various chlorinated organic
      chemicals and in waste incinerators. Dioxins are extremely stable in the
      environment and have a low turnover rate in the body--sometimes they are detected
      years after the original exposure. Of the dioxins, the most notoriously famous is
      the TCDD (2,3,7,8 tetrachlorodibenzo-p-dioxin). Dioxins exhibit high acute
      toxicity in various animal species. Humans, however, are considered less
      susceptible and so far there were no reported deaths following acute dioxin
      poisoning. Nevertheless, numerous adverse health effects are attributed to dioxin
      exposure. The most prominent is the chloracne--an acute acneiform eruption,
      usually appearing on facial skin. There is a solid evidence base that some
      dioxins are carcinogens. Other long-term deleterious effects of dioxin include:
      immunosuppression, effects on reproduction, impairments in developmental,
      neurological and cognitive functions in infants, increased risk for diabetes and
      cardiovascular diseases and various hormonal alterations. The action of dioxins
      resembles that of hormones, since their toxicity is mostly receptor-mediated.
      Dioxins manifest their toxicity in extremely low concentrations. Although there
      are compounds that exhibit their biological activity at even lower dose range
      (e.g. nerve gases), this potency of dioxins is considered extraordinary, since
      there is an every-day exposure to dioxins through environmental vectors mostly
      via the food chain. Until now, there is no antidotal cure for dioxins, but only
      symptomatic treatment combined with techniques that accelerate its excretion rate
      from the body.

PMID- 16281768
TI  - [Genital piercing].
AB  - Piercing is defined as puncturing an organ in order to place a jewel in the
      perforated site. There is almost no external organ in the human body that has
      escaped piercing. The origin of piercing traces back to the dawn of human
      history. Piercing is performed for decorative or symbolic purposes. Genital
      piercing (male or female) has recently extended into Western societies in general
      and to Israel in particular. The aim of genital piercing is said to be both
      decorative and for the enhancement of sexual pleasure. There are several types of
      genital piercing. The procedure is performed by non-medical persons, not within
      medical institutions, and may involve severe complications. Israeli legislation
      that regulates genital piercing is lacking.

PMID- 16281769
TI  - [And wine maketh glad the heart of man: is it so?--allergy to alcoholic drinks].
AB  - Adverse reactions to alcoholic drinks are common, especially in asthmatic
      patients. Since these drinks are the end product of a long process consisting of
      multiple ingredients, many factors may induce such reactions. This is a case
      study of a woman who has suffered from recurrent episodes of cutaneous eruption
      and dyspnea. Meticulous inquiry eventually revealed that drinking white wine was
      responsible for those symptoms. Grapes, barley, various fruits, alcohol,
      preserving substances like sulfite, biogenic amines like histamine and other
      ingredients can all be potential triggers of the adverse reactions to alcoholic
      drinks. On the other hand, alcohol has been shown to have various effects on the
      immune system including the allergic reaction. This case report and review of the
      literature may shed some light on this common yet unknown phenomenon.

PMID- 16281770
TI  - [Rembrandt and a lesson in anatomy was it just a dream?].

PMID- 16281771
TI  - [Explosion of cardiovascular risks in family practice].

PMID- 16281772
TI  - [Acid inhibitors for asthma patients].

PMID- 16281773
TI  - [What does the H. pylori eradication bring?].

PMID- 16281774
TI  - [Better to start from top?].

PMID- 16281775
TI  - [Weapons of mass destruction on our table].

PMID- 16281776
TI  - [Greater aim safety in intervertebral disk surgery? ( interview by Thomas
      Meissner)].

PMID- 16281777
TI  - [For coronary disease patients risky].

PMID- 16281778
TI  - [Caution, when the patient is confused!].

PMID- 16281779
TI  - [Pain remedies regardless of unclear diagnosis?].

PMID- 16281780
TI  - [Weight loss prevents hypertension].

PMID- 16281781
TI  - [The metabolic syndrome and mental illness: relevance, risk factors and practical
      consequences].
AB  - The prevalence of the metabolic syndrome and its sequelae (cardiovascular
      diseases and diabetes mellitus) is elevated in patients with depression and
      schizophrenic disorders in comparison with mentally healthy persons. A variety of
      factors have been proposed to explain this association. These include overlapping
      pathophysiological mechanisms, an unhealthy lifestyle (poor dietary choices,
      smoking, lack of exercise), genetic factors and a lack of compliance with
      therapeutic programs. In addition to this, attention is increasing being focused
      on the metabolic side effects of (atypical) neuroleptics. Cases of acute
      ketoacidosis may also be associated with the use of these substances. Since none
      of the neuroleptics currently commercially available can be guaranteed to be free
      of metabolic side effects, strict monitoring of depressive or schizophrenic
      patients receiving such treatment is mandatory.

PMID- 16281782
TI  - [Relationships between mental and cardiac diseases].
AB  - Affective and schizophrenic illnesses are associated with an elevated--in
      particular cardiovascular-related--risk of mortality. Patients with a cardiac
      disease who suffer from episodes of depression should be treated with selective
      serotonin reuptake inhibitors. Sertraline and citalopram have a low potential for
      interaction. Thioridazine, pimozid and ziprasidone are the substances that most
      commonly lead to lengthening of the QTc interval and thus to repolarization
      disorders. However, the results of studies carried out to date show that, in
      contrast to thioridazine and pimozid, ziprasidone has not so far been suspected
      of having an association with sudden heart death. Prior to starting treatment
      with tricyclic antidepressants or neuroleptics, a baseline ECG should be
      obtained. Follow-up ECG should be recorded and consideration given to possible
      drug interactions leading to cardiac arrhythmias, in particular when low-potency
      antipsychotics are used.

PMID- 16281783
TI  - [Precursors of stable hypertension. Office hypertension and normotension].

PMID- 16281784
TI  - [Deformation of the fist due to Taekwondo training].
AB  - Over a period of 25 years a 40-year-old taekwondo world champion had conditioned
      his hand for so-called "breaking championships", by repeatedly striking
      progressively harder materials (sand, dried peas, a mixture of dried peas and
      small stones, and such like). An MRI investigation revealed an augmentation of
      tissue between the heads of the metacarpals. The biomechanical effect resulting
      from this "smoothing" of the striking area of the fist is to reduce the peak load
      acting on the prominent bony elements on impact, and thus reduce the risk of
      injury. The build-up of tissue represents a response of connective tissue to
      repetitive microtrauma.

PMID- 16281785
TI  - [The situation of patients with dementia may be rectified by Gingko Biloba].

PMID- 16281786
TI  - [How a small Brandenburg town will catch physicians].

PMID- 16281787
TI  - [... but every EU practitioner can unexamined become general practice physician].

PMID- 16281788
TI  - [Success fee for pain therapy].

PMID- 16281789
TI  - [Fortuitous finding microhematuria].
AB  - The present article describes the procedure to be followed when the rapid urinary
      test is positive, and identifies possible diffential diagnoses.

PMID- 16281791
TI  - [What child's groin produces...].

PMID- 16281792
TI  - Religion can make you sick or help keep you well.

PMID- 16281793
TI  - The locus theologicus of U.S. Hispanic/Latino/a Theology and its implications for
      Clinical Pastoral Education (CPE) curriculum development.
AB  - The author examines the history of theological method based on the term locus
      theologicus, the refinement of this method by Liberation Theologians and U. S.
      Hispanic/Latino/a Theologians, and describes one experience of using contextual
      theology to develop curriculum for Second-Year Clinical Pastoral Education (CPE)
      Residents.

PMID- 16281794
TI  - Same-sex attraction, homosexual orientation, and gay identity: a three-tier
      distinction for counseling and pastoral care.
AB  - Given recent prevalence estimates most pastoral caregivers and counselors will
      work with persons who experience same-sex attraction (SSA). Many of the people
      who experience SSA will report such a consistency in the directionality and
      intensity of their attractions that they think of themselves as having a
      homosexual orientation. Others will integrate their experiences of SSA into a gay
      identity. What can facilitate pastoral care and counseling is an intentional use
      of this three-tier distinction: experiences of SSA, homosexual orientation, and
      gay identity. A discussion of this three-tier distinction is followed by specific
      suggestions for utilizing this conceptual framework as a resource in pastoral
      care and counseling.

PMID- 16281795
TI  - Correlates of compassion fatigue and burnout in chaplains and other clergy who
      responded to the September 11th attacks in New York City.
AB  - Participants at a June 2002 conference about the September 11th attacks were
      tested for compassion fatigue, compassion satisfaction, and burnout. The sample
      consisted of 343 clergy, including 97 chaplains. A total of 149 (43.4%) of the
      participants had responded as disaster-relief workers following the September
      11th attacks. The number of hours clergy worked with trauma victims each week was
      directly related to compassion fatigue among responders and non-responders.
      Compassion fatigue also was positively related to the number of days that
      responders worked at Ground Zero, while disaster-relief work with the American
      Red Cross reduced compassion fatigue and burnout. Clinical Pastoral Education
      tended to decrease compassion fatigue and burnout and increase compassion
      satisfaction in both responders and non-responders. Burnout was inversely related
      to age in both groups.

PMID- 16281796
TI  - A study of religion, ministry, and meaning in caregiving among health
      professionals in an institutional setting in New York City.
AB  - The clinical staff of a large metropolitan nursing home was surveyed about their
      religious practices, the degree to which they saw their work as a ministry, and
      the meaning they obtain from being caregivers. Age, race, gender, education, and
      various other measures were also taken. As hypothesized, religiosity made a
      significant positive contribution to participants' belief their work was a
      ministry to those in need. Multiple regression revealed that African American and
      older staff scored significantly higher on both dependent variables, whereas
      Caucasians were significantly less likely to view their work as ministry. Staff
      who worked with long-term patients derived significantly more meaning from their
      work, but they were no more likely to see it as ministry. Religiosity appears to
      enhance the meaning caregivers get from their work, and this may be beneficial to
      patients. Further research may identify other factors that enhance the meaning
      caregivers get from their work.

PMID- 16281797
TI  - Grief and critical care nursing: occurrence and resolution.
AB  - This article reports on research designed to assess the level of grief and the
      mechanisms of resolution experienced by critical care nurses as they relate to
      patient death. This prospective exploratory, descriptive study surveyed
      Registered Nurses (N=92) assigned to Critical Care Units at the University of
      Colorado Hospital in Denver, Colorado. Based on the findings, the author offers
      suggestions for ways to provide grief management education to staff as well as
      timely grief ministry by chaplains.

PMID- 16281798
TI  - The spirituality of People of Color living with AIDS in long-term care.
AB  - This article describes research results regarding the role of
      religion/spirituality among the chronically ill that highlights the benefits of
      religious beliefs and practices on patient health and well being. The author
      reports results from a questionnaire administered to People of Color living with
      AIDS who reside in a nursing home. The results suggest a strong spirituality as
      evidenced in a desire to communicate with God through frequent prayer and the
      reading of the patient's Holy Book. It includes high levels of hope, feelings of
      being loved, and attendance at religious services and classes held in the nursing
      home.

PMID- 16281800
TI  - Programmatic staff care in an outpatient setting.
AB  - Traditionally, chaplains have provided care for staff through consultation,
      informal conversation, grief work, and more formal counsel and ritual. This
      article discusses four programmatic approaches to staff care created in response
      to particular assessed needs: "Finding Soul" addresses staff care needs to find
      meaning and joy in their work and to contribute to the "soul" of the institution.
      "Existential Expedition" helps staff both deal with their accumulated grief and
      provide better direct care around existential issues being faced by their
      patients. "After Book" provides a way for staff to have closure with
      parents/families and to provide holistic care to families after discharge from
      the system. "The Labyrinth Program" provides staff with an opportunity to de
      stress and to attend to their emotional and spiritual well-being. Focused upon
      staff care, these programs also secondarily benefit both patients/families and
      the vision and mission of the institution.

PMID- 16281799
TI  - A teaching project for training family residents regarding the services of
      hospital chaplains.
AB  - In doing a curriculum evaluation for Behavioral Science training of Family
      Medicine Residents, it was determined that the knowledge of the work of the
      chaplains in inpatient care was somewhat limited. The Behavioral Science Educator
      initiated a collaborative project with the Department of Pastoral Care in order
      to facilitate an increased awareness of the chaplains' services, since the
      chaplains are part of the patient treatment team. This article is a description
      and evaluation of that project.

PMID- 16281801
TI  - Recalling the power of intimate engagement in clinical pastoral education's
      history.

PMID- 16281802
TI  - Idea of an "Order of Pastoral Care" presents problems on the national level.

PMID- 16281803
TI  - The need for an order of pastoral care bound to end in tears.

PMID- 16281804
TI  - Clinical Pastoral Education for Jews an enriching experience.

PMID- 16281805
TI  - The pastoral visit as Pas de deux.

PMID- 16281806
TI  - The bad-enough mother.

PMID- 16281807
TI  - Help in the midst of helplessness.

PMID- 16281808
TI  - Decisions at the end of life: a CPE supervisor's personal reflection.

PMID- 16281809
TI  - Summary judgment on patient's battery and negligence claims reversed. Mullins v.
      Parkview Hospital, Inc.

PMID- 16281810
TI  - Commencement of limitation period delayed by hospital's lack of cooperation.

PMID- 16281811
TI  - [Treatment options in monogenic disorders of keratinization].

PMID- 16281812
TI  - [Melanoma-stroma interactions and melanoma progression].
AB  - Cutaneous melanoma is an aggressive tumor which can metastasize early in its
      course. Not only the melanoma cells but also the tumor microenvironment play an
      important role in tumor development and progression. We review the structural and
      functional aspects of interactions between melanoma cells and the stroma and
      discuss some clinical implications.

PMID- 16281813
TI  - [Sentinel lymph node biopsy in malignant melanoma--an update].
AB  - Ten years after the introduction of the sentinel lymph node biopsy technique in
      the management of malignant melanoma, it is time to take stock. The complex
      method has proved itself sufficiently sensitive, although a certain percentage of
      false-negative histological results have to be taken into account. Presently, it
      is still a point at issue whether sentinel lymph node biopsy should be regarded
      as the standard of care in high-risk patients. Three prospective multicentre
      trials have failed to demonstrate a survival benefit resulting from elective
      lymph node dissection. In contrast, a retrospective multicentre study has
      recently shown that patients with node metastases diagnosed by the sentinel
      procedure benefit from early excision of their nodal disease in terms of overall
      survival, as compared to patients with delayed dissection of palpable nodes.
      Studies worldwide have established the pathologic status of the sentinel lymph
      node biopsy as the most important prognostic factor for recurrence and survival
      after the excision of primary melanoma. As with any invasive staging procedure,
      sentinel lymph node biopsy should have demonstrated therapeutic consequences.
      Unfortunately, an unequivocally acknowledged adjuvant therapy is lacking.
      Moreover, the impact of complete lymph node dissection after positive sentinel
      biopsy on survival or local disease control has not yet been clarified.

PMID- 16281814
TI  - Bexarotene--an alternative therapy for progressive cutaneous T-cell lymphoma?
      First experiences.
AB  - BACKGROUND: A standard therapy for advanced cutaneous T-cell lymphomas has not
      yet been defined. Bexarotene is a new retinoid x receptor-specific retinoid that
      has been approved for systemic second-line therapy for cutaneous T-cell lymphomas
      in the USA and Europe. In order to evaluate the efficacy of bexarotene in
      cutaneous T-cell lymphomas, a pilot trial was initiated. PATIENTS AND METHODS: In
      a pilot project 10 patients with advanced cutaneous T-cell lymphomas, who had
      received a variety of previous treatments, were treated with bexarotene at the
      departments of dermatology in Munster, Minden and Charite Berlin, Germany. The
      patients received bexarotene at a dose of 300 mg/m2 body surface daily. According
      to the percentage of tumour reduction and affected body surface, the response
      rates were divided in complete and partial remission, stable disease and
      progressive disease. Laboratory parameters i.e. cholesterol, triglycerides
      transaminases, T3, T4, and TSH were screened regularly. RESULTS: In 2 patients a
      short partial remission was achieved; however, after a few weeks progression
      followed. In 4 patients a lasting stabilisation was obtained. The other 4
      patients showed a progressive disease during therapy. 6 patients developed
      hypertriglyceridemia with levels up to 2000 mg/dl; therapy had to be suspended in
      3 patients because of these adverse drug events. CONCLUSION: Weighing benefits
      and risks, bexarotene can at present not be recommended as standard therapy in
      the treatment of patients with progressive cutaneous lymphomas.

PMID- 16281815
TI  - [Solar keratosis: from precancerous lesion to pre-invasive squamous cell
      carcinoma--therapeutic approach with a bioinductive method].
AB  - BACKGROUND: Solar keratoses are precancerous lesions in chronically UV-damaged
      skin with histological features consistent with pre-invasive squamous cell
      carcinoma. They require therapeutic intervention in order to prevent progression
      towards invasive carcinoma. Treatment options include topical medications and
      destructive methods. We report on a new approach--topical bioinductive therapy
      with imiquimod 5% cream. PATIENTS AND METHODS: In a prospective case series, 7
      patients with solar keratoses have been treated with topical imiquimod 5%. The
      cream was applied 5 days/week over 2 weeks. After end of treatment, the outcome
      was assessed at regular control visits and, in some cases, histologically
      confirmed. One patient was followed up as untreated control. RESULTS: In 6 of the
      7 treated patients, the lesions cleared completely; one patient did not respond.
      The patients did not show new solar keratoses during a follow-up period of about
      2 years. The untreated patient showed spontaneous clearance of his keratoses.
      Local skin reactions during treatment included erythema, oedema and erosions in
      varying degrees, all of which completely resolved. CONCLUSIONS: Bioinductive
      therapy with imiquimod 5% cream represents a promising therapeutic approach for
      cutaneous precancerous lesions such as solar keratoses.

PMID- 16281816
TI  - [Porokeratotic eccrine ostial and dermal duct naevus (PEODDN)].
AB  - The porokeratotic eccrine ostial and dermal duct naevus or PEODDN represents a
      very rare hamartoma of the eccrine sweat glands. A 16-year old boy had developed
      subtle hyperkeratotic skin lesions on his right hallux at six months of age. When
      he was eight years old, he developed similar lesions on his right palm.
      Clinically the lesions were coniform hyperkeratoses. The histopathological
      examination confirmed the diagnosis of a PEODDN showing typical cornoid lamella
      where the eccrine secretory ducts penetrated the epidermis. Although
      porokeratotic eccrine ostial and dermal duct naevi are generally considered as
      unresponsive to conservative treatment, in our patient topical treatment with
      tazarotene gel 0.1% resulted in a significant improvement within three weeks.

PMID- 16281817
TI  - [Smoking -- effects on the skin].

PMID- 16281818
TI  - [Livid red nodules on the chest, back and upper arms in an 86-year-old man].

PMID- 16281819
TI  - [Recommendations for quality management in dermatologic clinics and dermatologist
      practices].

PMID- 16281820
TI  - [Rudolf Happle -- the 65th birthday].

PMID- 16281821
TI  - Antifungal activity of Boerhavia diffusa against some dermatophytic species of
      Microsporum.
AB  - Various extracts petroleum ether, chloroform, ethyl acetate and ethyl alcohol) of
      aerial and root parts of Boerhavia diffusa was sereened for Antitungal activity
      (Inhibition in sporulation) against dermatophytic fungi Microsporum gypseum, M.
      fulvum and M. canis by using broth dilution method. Extracts of aerial part not
      show any noticeable antifungal activity. Ethyl acetate extract of root part of
      the plant was found to be most effective of against target fungal species. The
      maximum inhibition of mycelial growth was observed for M. gypseum (78.83%)
      followed by M. fulvum (62.33%) and M. canis (42.30%) of ethyl acetate in the test
      concentration of 1000 microg/ml 24 hours of incubation. The sporulation of target
      fungal species decreases with increasing supplementation of phytoextract,
      confirms the presence of some antifungal phytochemical moiety in roots of the
      plant.

PMID- 16281822
TI  - Antifungal activity of some actinomycetes isolated from various habitats.
AB  - A total of 287 actinomycetes were isolated from 79 samples collected from five
      different habitats i.e., cultivated field soil (CFS), garden soil (GS), compost
      (CM), decaying organic matter (DOM) and stored agricultural products (SAP) of
      different localities of Sagar, Madhya Pradesh (23 degrees 50 degrees N latitude
      and 78 degrees 40 degrees E longitude). These were screened for antagonistic
      activity against Candida albicans, Aspergillus niger, Microsporum gypseun and
      Trichophyton sp. using 'Cross streak method'. Out of these, a total of 166
      isolates were found antagonistic to Candida albicans, while 164, 134 and 132
      actinomycetes showed antagonistic properties against A. niger, M. gypseum and
      Trichophyton sp., repectively. A total of 17 isolates showed very strong
      anticandidal activity causing total inhibition in the growth of C. albicans and
      hence, distribution of isolated test actinomycetes in different habitats and the
      cultural and antagonistic properties of selected 17 promising strains are
      reported here.

PMID- 16281823
TI  - Strain improvement studies on production of cephalosporin C from Acremonium
      chrysogenum ATCC 48272.
AB  - Strain development for antibiotic production has been an essential prerequistie
      for efficient production process. Studies were carried out to produce high
      antibiotic yield strain by using UV and N-methyl-N1-nitro-nitrosoguanidine (NTG)
      as mutagens. A superior mutant (PNTG-22) with a productivity of 2.4 time (810
      1995 microg/ml higher than, the parent strain was produced.

PMID- 16281824
TI  - Characterisation of a new bioactive actinomycete AUB N5/8 from marine sediments.
AB  - Actinomycetes were isolated from marine sediments off Machilipatnam coast of
      Andhra Paradesh by plating on Starch-Casein Agar medium. From which one isolate
      AUB N5/8 was selected for detailed morphological, cultural, physiological and
      biochemical studies. The genera encountered were, Streptomycetes. Studies were
      compared with known strain S. baarinenisis (ISP 5232). It showed enough
      significant difference to create the status of a separate species for our isolate
      AUB N5/8. Hence it was designated as Streptomyces kavutarensis Sp.nov.

PMID- 16281825
TI  - Screening of actinomycetes isolated from soil samples of Ajmer, Rajasthan for
      antimicrobial activity.
AB  - Several strains of actinomycetes were isolated from soil samples collected from
      various localities ofAjmer district. These isolates were tested for their
      antagonistic proerties against few test organisms viz. Bacillus subtilis,
      Escherichia coli, Pseudomonas aeruginosa, Staphylococcus sp., Saccharomyces
      cerevisiae and Aspergillus niger. Some of these actinomycete strains exhibited
      antimicrobial activity against bacteria, no antifungal activity was observed. Six
      such isolates were selected for detailed morphological, cultural, physiological
      and biochemical studies for identification. Five of these were identified as
      members beloging to the genus Streptomyces and the remaining one belonging to the
      genus Actinoplanes.

PMID- 16281827
TI  - Healing-promoting action of rhinax with dual action on chronic gastric and
      duodenal ulcers induced by acetic acid in rats.
AB  - Healing promoting actions of Rhinax, a multiconstituent herbal preparation, was
      investigated in chronic gastric and duodenal ulcer models induced by acetic acid
      in rats and the effects were compared with those of famotidine by gross of
      histological evaluation. Rhinax markedly promoted the well balanced healing of
      gastric ulcer at oral does of 25-100 mg/kg x 2 /day, as evidenced by the
      reduction of ulcer, regeneration of mucosa and proliferation of connecitve
      tissue. Rhinax caused an increase in gastric mucosa secretion in all the
      regenerated mucosa around the gastric ulcers. Famotidine failed to promote the
      healing of gastric ulcers at 100 mg/kg x 2/ day p.o. Rhinax also significantly
      accelerated the healing of acetic acid -induced duodenal ulcers as well
      famotidine. These results indicate that Rhinax is characterised by a potent
      promoting action on the healing of chronic ulcers, suggesting that the increase
      in gastric mucus secretion might be associated with the antiulcer action of
      Rhinax in rats.

PMID- 16281826
TI  - Production of industrially important enzymes by some actinomycetes producing
      antifungal compounds.
AB  - Seventeen strains of actinomycetes antagonistic to yeast and moulds have been
      tested for their ability to produce amylase, lipase, gelatinase and caseinase
      using solid media containing starch, Tween-20, gelatin and skimmed milk,
      respectively, Enzyme producing potential of test strains is expressed in ternis
      of relative enzyme activity (REA). Actinomycetes strain Streptomyces somaliensis
      GS 1242 and Streptomyces sampsonii GS 1322 showed higher amylase production (REA
      6.5) while maximum lipase activity was noted in Streptomyces strain SAP 1089 (REA
      7.0). Gelatinase activity was noted higher is S. sampsonii GS 1322 (REA 9.6) and
      S. somaliensis GS 1242 (REA 8.8). Enzyme producing potential of these strains has
      been discussed in terms of their industrial significance.

PMID- 16281828
TI  - Investigation on the gastroprotective and antidiarrhoeal properties of Aegle
      marmelos unripe fruit extract.
AB  - The Study was designed to verify the gastroprotective and antidiarrhoeal effects
      of unripe fruit extract of Aegle marmelos Corr. The gastroprotective function of
      this extract was evaluated in rats against gastric mucosal damage induced by
      hypothermic restraint stress, absolute ethanol, and indomethacin, whereas the
      antidiarrhoeal activity was investigated by studying the influence on
      gastrointestinal transit as measured by a charcoal marker and on castor oil
      induced accumulation of intestinal fluid in mice and also on contractile
      responses evoked by acetylcholine, histamine, serotonin, and barium chloride in
      isolated guinea-pig ileum, the results demonstrated that pretreatment of animals
      with unripe fruit extract (50 and 100 mg/kg, i.p.) produces a significant
      inhibition of gastric lesion induced by ethanol but not those induced by
      restraint stress or indomethacin and suggest a probable involvement of a
      prostaglandin-independent mechanism of gastroprotection. At similar doses, both
      the intestinal transit as well as the accumulation of intestinal fluids induced
      by castor oil in mice were significantly inhibited by raw fruit extract.
      Furthermore, the extract antagonized the contractile responses evoked by
      different agonists on guinea-pig ileum in vitro and its inhibitory potential for
      the drugs are in the order of acetylcholine > histamine > serotonin > barium
      chloride. Taken together, these results point out a possible antidiarrhoeal
      effect of unripe fruit extract of A. marmelos Corr., since inhibition of
      intestinal motility and secretion can control clinical diarrhoea.

PMID- 16281829
TI  - [Polyneoplasia in the structure of urologic cancer morbidity].
AB  - A retrospective analysis of case histories made for cancer patients treated from
      1980 to 2004 has established 2233 cases of urological cancer. Of them, 540
      (24.2%) had polyneoplasia. Urogenital cancer most frequently runs in parallel
      with neoplasia of the colon, stomach, kidney, skin and prostate. These patients
      should be adequately examined and followed up to detect primary metachronic tumor
      early and to treat radically subsequent tumors.

PMID- 16281830
TI  - [The role of a positive surgical margin after retropubic radical prostatectomy in
      prognosis of recurrent prostatic cancer].
AB  - To estimate the occurrence of positive surgical margins (SM) in conduction of
      radical retropubic prostatectomy and SM role in development of the recurrence, we
      studied 216 surgical patients with prostatic cancer aged 41 to 73 years. Stages
      T2a,b, T3a, T1 and T3b were detected in 41.8, 35.6, 18.7 and 3.9% patients,
      respectively. A positive SM was verified in 68 of 193 (35.2%) patients. Of them,
      36 (52.9%) patients had a focal (a single or short SM), while 32 (47.1%) patients
      had a long SM. The recurrence occurred in 31 (16.1%) cases, primarily in a long
      SM. In SM-free patients (group 1) one-year survival was 82% being very close to
      that in group 2 with a focal SM (83%). The differences between the groups were
      also minimal by three-year survival (75 and 73.6%, respectively). Thus,
      recurrence-free survival in the focal process and a short SM differs by three
      year survival in the groups insignificantly. The period between month 12 and 24
      is most risky in respect to recurrences in a short SM. Patients with a long SM
      had maximal number of prostatic cancer recurrences.

PMID- 16281831
TI  - [Adrenal tumors: topical diagnosis and surgical outcomes].
AB  - A total of 128 adrenalectomies were made for catechol-producing tumor (n = 69),
      mineralocorticism (n = 27), primary and metastatic adrenal cancer (n = 20), other
      tumors (n = 12). A stable hypotensive result after adrenalectomy was observed in
      97.1, 66.8% patients with pheochromocytoma and mineralocorticism, respectively.
      The rest patients improved, i.e. their malignant hypertension converted to a
      benign one. If cancer involves the upper segment of the kidney, the tumor often
      invades the adrenal. Therefore, pre- and intraoperative search for adrenal tumor
      must be made.

PMID- 16281832
TI  - [Plastic repair of the urinary tract with intestinal graft].
AB  - Enteroplasty of the urinary tract was made in 224 patients (175 male and 49
      female, age 21-72 years): enteroplasty of the ureter (n = 25), augmentation
      cystoplasty (n = 38), replacement of the urinary bladder after radical cystectomy
      for cancer (n = 161). The grafts were made of the small intestine segments--149
      (66,5%), sigmoid--45 (20%), stomach--25 (11.2%), appendix--3 (1.3%). Total
      postoperative lethality reached 2.7%. Early and late complications occurred in
      26.8 and 32.2% patients, respectively. In half the cases complications were
      related to the derivation method. Fifty three reoperations were made, most
      frequent of them was percutaneous nephrostomy. Thus, use of gastrointestinal
      tract segments for replacement of the urinary tract provides adequate urine
      outflow from the kidneys, close to natural micturition. Introduction of advanced
      methods of urine derivation prevents formation of urinary fistulas and improves
      quality of the patients' life.

PMID- 16281833
TI  - [One-stage transurethral resection of the urinary bladder and the prostate in
      patients with superficial cancer of the urinary bladder combined with benign
      prostatic hyperplasia].
AB  - Combination of urinary bladder cancer (UBC) with benign prostatic hyperplasia
      (BPH) is a prognostically unfavourable factor. To assess clinical efficacy of one
      stage transurethral resection of UBC and BPH in combination with adjuvant
      immunotherapy, we examined 181 patients with UBC stage Tis, Ta-T1 and BTH. All
      the patients have undergone one- and two-stage endoscopic operations. TUR of the
      urinary bladder and the prostate was made in 87 patients. Stage-by-stage TUR of
      the urinary bladder and TUR of the prostate were made in 94 controls. We
      conducted postoperative immunotherapy with BCG vaccine (imuron) as an adjuvant
      therapy in 114 (63%) patients. Postoperative UBC recurrence occurred in 124
      (68.5%) patients: 49 (56.3%) patients of the study group and 75 (79.7%) controls
      (p < 0.05). Reoperation (TUR of the urinary bladder) was performed in all cases
      of UBC recurrence. Five-year survival in the study group was 71% and 68.0%
      survived in the control group (p > 0.05). The conclusion is made that in
      combination of superficial UBC with BPH indications appear for TUR of the urinary
      bladder and TUR of the prostate with adjuvant immunotherapy. Early elimination of
      infravesical obstruction lowers UBC recurrence rate and improves the patients'
      quality of life.

PMID- 16281834
TI  - [Efficacy of ciprofloxacine antibiotic prophylaxis of infectious complications
      after TUR of the prostate].
AB  - We compared efficacy of preoperative prophylactic antibiotic treatment (PPAT)
      with cyprofloxacine used orally (0.5 g), intravenously (0.4 g) and routine
      antibiotics in TUR of the prostate. A multicenter open randomized study covered
      120 patients. PPAT efficacy was estimated by the rate of urinary infection (UI),
      frequency and duration of antibiotic treatment in the postoperative period,
      hospitalization duration. All the patients were divided into three groups: 39
      patients of group 1 received oral cyprofloxacine 90-120 min before TUR of the
      prostate, 38 patients of group 2 received intravenous cyprofloxacine 30-60 min
      before TUR, 43 patients of group 3 (control) received routine antibiotic
      prophylaxis. The following results were obtained: 24-48 hours after the operation
      no cases of UI in group 1, 11.5 and 11.6% in groups 2 and 3, respectively, (p =
      0.048); 7 days after TUR--UI in all the groups (2.6, 20, 23.3%, respectively); 14
      days after TUR--UI in 5.1, 28.6, 27.9% patients, respectively. Mean duration of
      hospital stay was 11.7 +/- 7.6 days in group 1, 12.1 +/- 8.1 days in group 2,
      12.5 +/- 7.8 days in group C (p > 0.05). Postoperative antibiotics were given to
      16.7, 34.1 and 68.9% patients, respectively. Thus, cyprofloxacine in group 1
      lowered UI risk and postoperative antibiotics significantly, in group 2 it had no
      influence on UI rate but reduced postoperative antibiotics significantly.

PMID- 16281835
TI  - [Prostatilen effects on voiding disorders in patients with benign prostatic
      hyperplasia].
AB  - The authors review the experience with prostatilen treatment gained in the
      urological clinic of the St-Petersburg State Medical University and analyze
      treatment outcomes for 96 patients with benign prostatic hyperplasia (BPH) aged
      from 51 to 89 years. Prostatilen proved its efficacy in relieving manifestations
      of infravesical obstruction in BPH, therefore, prostatilen administration in the
      treatment of patients with initial or moderate subjective and objective symptoms
      is justified. Dimexide suppositoria containing 30 mg of prostatilen are
      preferable.

PMID- 16281836
TI  - [Impase in the treatment of erectile dysfunction].
AB  - The authors review epidemiology, classification, etiology and pathogenesis of
      erectile dysfunction (ED), its diagnosis and treatment with a focus on mechanisms
      of action and efficacy of the drug impase. Impase is the drug of superlow doses
      of affinitively purified potentiated antibodies to human endothelial NO-synthase.
      The drug regulates NO synthesis in the cavernous bodies, enhances an NO relaxing
      action on their smooth muscles and blood flow in the penis under sexual
      stimulation. The drug demonstrated its high efficacy and safety in many clinical
      trials. Impase trial performed in the Research Institute of Urology in 2004 has
      found that impase is more effective in long-term administration, most of the
      examinees exhibited a clinical response only after one month of regular intake.
      The drug can be used both as the first-line monotherapy of ED and combined
      treatment of this disease. Clinical recommendations for practitioners on
      administration of impase are provided.

PMID- 16281837
TI  - [An evidence-based approach to writing reviews as illustrated by treatment of
      erectile dysfunction].
AB  - Reviews integrate the data from original sources of information on the given
      topic. The quality of the review of literature depends on the quality of initial
      information. The development of evidence-based medicine demands higher standards
      from clinical trials. The authors analyse available information on the treatment
      of erectile dysfunction basing on standard international requirements for
      clinical trials. A checking list is available for standardization of clinical
      assessment. The data obtained is ranged by the degree of statistical
      significance. Basing on the evidence-based approach, the conclusion on efficacy
      of the following modern drugs in the treatment of erectile dysfunction are made:
      sildenafil, iochimbin, prostaglandin E1 and tadalafil. The conclusion on efficacy
      of the other drugs against erectile dysfunction is impossible in view of
      methodological drawbacks of the trials.

PMID- 16281838
TI  - [Testosterone production by tumor tissue in partial androgen deficiency in aged
      men (PADAM)].
AB  - The aim of the study was examination of cause-effect relationships between PADAM,
      extragonadal production of androgens and high proliferative activity in aged men.
      The study group included 15 patients aged between 53 and 79 years with prostatic
      cancer (n = 5), urinary bladder cancer (n = 5) and cancer of the rectum (n = 5).
      Control samples of tissues of the prostatic gland, urinary bladder and rectum
      were obtained from dead bodies of men at the age between 18 and 29 years killed
      in the accidents at the age from 18 to 29 years. Testosterone levels in the
      tissues of peritumor zone of the prostate, in tumor tissue of patients with
      cancer of the prostate, urinary bladder and the rectum were higher than in blood
      serum. In prostatic cancer, testosterone in the tumor tissue was higher than in
      the tissues of prostatic peritumor zone. The values of Histochemical score AR of
      the peritumor zone in prostatic cancer patients were higher than those of the
      control group. It was detected that ER, PR, bcl-2, Ki-67 and p53 in prostatic
      tissue of young controls were absent while in patients with prostatic cancer
      these factors were expressed in the peritumor zone. In cancer of the urinary
      bladder, peritumor zone showed expression of PR, bcl-2, Ki-67 and p53, while no
      such expression was in the controls. ER, bcl-2, Ki-67 and p53 were registered in
      the peritumor zone of patients with cancer of the rectum but the controls had
      neither ER, bcl-2 nor p53 while Ki-67 expression in rectal cancer was higher than
      in the controls. The results of the study suggest that testosterone production by
      some tumors and tissues of the peritumor zone accompanied with high proliferative
      activity and dysregulation of the cell cycle is secondary to PADAM. These changes
      arise to compensate testicular deficiency and are manifestations of metabolic
      syndrome (X-syndrome). In this situation immune system fails to utilize all
      atypical cells.

PMID- 16281839
TI  - [Cavernous vegetative innervation and hemodynamics in patients with fibroplastic
      induration of the penis and erectile dysfunction].
AB  - Different versions on pathogenesis of Peirony's disease (PD) and erectile
      dysfunction in this disease made us to investigate cavernous innervation and
      hemodynamics in patients with fibroplastic induration of the penis. We have
      detected characteristic changes of cavernous electric activity and histochemical
      picture in biopsies of all our patients with PD. Of them, 61% had cavernous
      hemodynamic disorders. Our findings suggest that early affection of cavernous
      innervation may trigger PD pathogenesis and erectile dysfunction in this disease.

PMID- 16281840
TI  - [Congenital penile deviation: an integral diagnostic approach to correction].
AB  - A comparative analysis of diagnostic examination of 130 men with isolated
      congenital erectile penile deviation (EPD) aged 14-22 years (mean age 17 years)
      has demonstrated that true EPD can be determined objectively only at adequate
      erection. Therefore, the diagnosis should be based not on subjective opinion of
      the patient but on the results of artificial pharmacological erection or viagra
      test in combination with visual erotic and genital stimulation. Vacuum erection
      test is not justified. In patients with congenital EPD rigidity depends much on
      correlation between perfusion volume and functional volume of the penis
      (cavernous volume). The problem of congenital EPD can be formulated as the
      problem of "long penis". Measurements of the penis in the group of 54 patients
      with congenital EPD registered a low penile coefficient in 67% cases while a mean
      length of the penis in all the examinees was longer than a mean standard one and
      was about 13 cm in relaxed condition. EPD patients often suffer from
      asthenodepressive disorders deteriorating the copulative function. Psychotherapy
      and medication of the depressive syndrome result in stabilization of the
      psychological condition improving quality of life 1.3 times. Thus, an integrative
      diagnostic and therapeutic approach, due selection of the patients for operative
      correction of penile deviation can improve quality of the treatment aimed both at
      correction of erectile malformation and psychosexual adaptation of the patients.

PMID- 16281841
TI  - [The role of somatosensory evoked potentials in prognosis of efficacy of tibial
      neuromodulation in patients with hyperactive urinary bladder].
AB  - Registration of evoked brain potentials was used as a non-invasive and an
      objective method of diagnosis of the CNS diseases. Somatosensory evoked
      potentials (SSEP) in response to stimulation of the tibial nerve were studied in
      patients with hyperactive urinary bladder (HUB) to clarify SSEP role in prognosis
      of tibial neuromodulation (TNM) efficacy. Urodynamic parameters and SSEP were
      examined in 13 patients with symptoms of urinary accumulation disorders.
      Neurogenic HUB was diagnosed in 6 patients, idiopathic one--in 7 patients. TNM
      was delivered in 30-min weekly sessions (n = 12). Six of seven patients with a
      cortical potential responded to TNM. Of six cortical nonresponders a positive
      result was achieved only in two. Thus, patients with the cortical potential
      demonstrate better effect of TNM than those without the potential. It is
      suggested that TNM influences both sacral and supraspinal center of urination.

PMID- 16281842
TI  - [Efficacy of natural therapeutic factors of Belokurikha health resort in
      rehabilitation of patients with chronic prostatitis].
AB  - A total of 135 patients with chronic prostatitis have undergone rehabilitation in
      Belokurikha health resort. Of them, 35 patients of group 1 received basic therapy
      (nitrosiliceous baths, therapeutic exercise, massage of the prostate,
      psychotherapy); 40 patients of group 2 received basic therapy plus rectal tampons
      with sulphide mud from the lake Gorkoye of the Altai Administrative Area; 60
      patients of group 3 were given basic therapy plus rectal lavage of the prostate
      location with nitrosiliceous thermal water of Belokurikha health resort.
      Treatment efficacy was assessed by scales of the symptoms and sexual disorders,
      ejaculate tests, testosterone levels, immune status, results of Doppler vascular
      mapping of the prostate. The highest effect was achieved in group 3 (87.3%
      response). This therapy relieves inflammation, stimulates a sexual function,
      improves hemodynamics in the prostate, raises the number and motility of
      spermatozoa, corrects immune disorders, normalizes testosterone concentration in
      the blood. In group 2 the response was obtained in 81.6% patients. This treatment
      improves hemodynamics, raises the number of spermatozoa. In group 1 the effect
      was observed in 60.4% patients, it manifested with an insignificant improvement
      in prostatic hemodynamics, spermatogenesis, hormonal and immune systems.

PMID- 16281843
TI  - [Lipids content in renal tissue membranes in patients with urolithiasis and
      secondary pyelonephritis].
AB  - We studied cytomembranes of the interstitial tissue of renal medullary layer
      obtained by lifetime biopsy of renal tissue in the course of pyelolithotomy in 46
      patients with urolithiasis and secondary pyelonephritis. Biopsy structure was
      controlled with histological methods using standard staining. Basic phospholipids
      and cholesterol fractions in renal tissue cytomembranes were assayed at thin
      layer chromatography. The findings show significant changes in a nephron
      cytomembrane lipid phase in patients with urolithiasis and secondary
      pyelonephritis. There was a structural rearrangement of lipid biolayer of renal
      tissue cell membranes in response to microbial inflammation. Thus, use of
      membrane-stabilising drugs are grounded in patients with secondary pyelonephritis
      and urolithiasis.

PMID- 16281844
TI  - [Triombrast in diagnosis of urological diseases].
AB  - Radiocontrast substances have a significant role in x-ray diagnosis of urological
      diseases. Diagnostic and cost-effect efficacy, delivery, storage life are
      described for radiocontrast substance triombrast (sodium amidotrizoate) of
      Ukraine production (Kiev). The review was based on the authors' experience and
      results of clinical trials.

PMID- 16281845
TI  - [Combined treatment of papillary tumors of the pelvis and ureter of the solitary
      kidney in combination with ureteral endoprosthesis].

PMID- 16281846
TI  - [Vardenafil: long-term and continuous treatment of severe erectile disorders].
AB  - Two cases are analysed to show possibility of severe erectile dysfunction (ED)
      treatment with long-term and regular intake of phosphodilesterase-5 (PDE-5)
      vardenaphil. A 39-year-old patient had cavernous fibrosis due to intracavernous
      introduction of vasoactive medication. Vardenafil was taken in a dose 20 mg in
      the evening for 6 months. At control examination ED relieved to a mild degree.
      Further intake of vardenaphil on demand is recommended. The other man 22 years of
      age had a severe erectile dysfunction after hip bones fracture and subsequent
      reconstruction of the urethra. He received vardenafil in a dose 10 mg in the
      evening for 3 months. After the treatment ED improved to a mild degree and
      further on-demand intake is recommended.

PMID- 16281847
TI  - [A metachronic metastasis of renal cell carcinoma in the ureteral stump].

PMID- 16281848
TI  - [Epidemiology of urolithiasis].

PMID- 16281849
TI  - [Current principles of conservative treatment of urine incontinence in women].

PMID- 16281850
TI  - [Surgery for the thymoma combined with pure red cell aplasia and myasthenia
      gravis].
AB  - Pure red cell aplasia (PRCA) and myasthenia gravis (MG) are respectively combined
      with thymoma, however, these 3 complications are extremely rare coexisted as a
      clinical triad. A 73-year-old female with mediastinal tumor found in 2000 was
      pointed out anemia in June 2002. As PRCA was diagnosed by the bone marrow
      examination, blood transfusion had been performed. By a chest computed tomography
      (CT), a thymoma in size of 7 x 5 cm in diameter was recognized in the anterior
      mediastinum. The serum level of anti-acetylcholine receptor antibody was elevated
      to be 35 nmol/l. MG was simultaneously diagnosed with a decreased power of neck
      muscle. The extended thymectomy was performed in August 2002, and pathological
      diagnosis disclosed a 'type AB' by World Health Organization (WHO)
      classification. After the operation, the decreased power of neck muscle had been
      improved, however, PRCA had not been remitted in the early-postoperative term.
      Blood transfusion had been required (2-4 units/1-2 weeks) for the postoperative 7
      months' term. A cyclosporin (250 mg/day) as an adjuvant therapy was administered
      in April 2003. One month later, the patient's serum level of Hb had been over 10
      g/dl without blood transfusion. The patient has been followed up with reducing
      the dose of cyclosporin. CONCLUSIONS: Surgery for a thymoma combined with PRCA
      and MG was effective for MG but not for PRCA in an early-postoperative term,
      however, a multimodality therapy with immunosuppressant as a postoperative
      adjuvant should bring a favorable outcome to patient's clinical data, and the
      postoperative long-observation must be critical in this case.

PMID- 16281851
TI  - [Early and late results and problems of coronary artery bypass grafting in
      patients over 80-year-old].
AB  - This study evaluated the validity of coronary artery bypass grafting (CABG) in
      patients over 80-year-old investigating the early and late result, patient's
      opinion to the surgery, and change of activities of daily living scale. From July
      1993 to September 2002, consecutive 94 patients over 80-year-old were performed
      CABG in our institution. The group consisted of 43 female patients, and mean age
      of 82.6 years. Of these patients, 36 were operated conventional CABG (CABG group)
      and 58 patients were operated with off-pump CABG (OPCAB) group. There were no
      significant differences between 2 groups in preoperative characteristics except
      for anemia and hypertension. Operative results, including mortality, number of
      distal anastomoses, operative time had no significant differences between 2
      groups. But maximum CK-MB fraction was higher in CABG group. There were 4
      operative deaths, indicating operative mortality was 4.3%. Late results showed
      overall survival rate at 3 years was 81.1% and cardiac event free survival rate
      at 3 years was 88.8%. Questionnaire revealed over 80% patients were satisfied
      with the surgery but less than 40% patients felt activities of daily living (ADL)
      scale was improved. Operative results of CABG in octogenarians were satisfied,
      but more efforts to remain patient's high ADL were mandatory.

PMID- 16281852
TI  - [Concomitant off-pump coronary artery bypass and left lower lobectomy for lung
      cancer with pneumoconiosis].
AB  - Surgical strategy for patients for lung cancer with coronary disease remains
      controversial. We performed concomitant off-pump coronary artery bypass grafting
      (off-pump CABG: OPCAB) and left lower lobectomy with ND 2a lymph nodes dissection
      for lung cancer with pneumoconiosis. After CABG, due to fixed adhesion of
      peribronchial lymph node, left lower lobectomy was hard to carry out.
      Postoperative management was done with much difficulty for massive sputum and
      pneumonia caused by chronic inflammatory lung disease. As a result, postoperative
      course has been uneventful for 2 years after operation. In the concomitant OPCAB
      and lung resection with chronic inflammatory lung disease, whether the
      synchronous or 2 periods operation was appropriate was still unknown. We think
      that careful pre- and intraoperative assessment for this disease is important.

PMID- 16281853
TI  - [Pulmonary pleomorphic carcinoma].
AB  - Pleomorphic carcinoma is a rare primary pulmonary malignancy. We report 2
      surgical cases of pulmonary pleomorphic carcinoma. The first case was a 71-year
      old male. Chest computed tomography (CT) showed a rapidly growing tumor with
      irregular density. Transbronchial lung biopsy revealed the tumor to be malignant.
      Left lower lobectomy was performed. Pathological diagnosis was pleomorphic
      carcinoma (pT2N2M0, stage IIIA). He died 8 months after surgery due to brain
      metastasis and mediastinal lymph node metastasis. The second case was a 74-year
      old male who complained of bloody sputum. Chest CT showed a tumor with cavity in
      the right middle lobe. Brushing cytology under bronchofiberscopy revealed
      atypical cell. Right middle lobectomy and partial resection of the right lower
      lobe were performed. Pathological diagnosis was also pleomorphic carcinoma
      (pT2N0M0, stage IB). He has no findings of recurrence nor metastasis 15 months
      after the operation.

PMID- 16281854
TI  - [Comparison of right ventricular function between prevention and enlargement of
      pulmonary valve annulus after repair of tetralogy of Fallot; mid-term results].
AB  - Total of 41 patients with tetralogy of Fallot (TOF) who underwent intracardiac
      repair from 1993 to 1998 were divided into 2 groups: preservation (n = 14) or
      enlargement (n = 27) of the pulmonary valve annulus. The procedure was decided on
      the Z value of the annular size: above or under -2 SD of the standard value.
      Although postoperative right ventricular (RV) diastolic volume (RVEDV) and
      cardiothoracic ratio (CTR) were larger than the preservation group and pulmonary
      regurgitation (PR) existed in the enlargement group, RV pressure was decreased
      and central venous pressure (CVP) was low and RV contraction was preserved. The
      exercise capacity was also good and no significant arrhythmia was recognized. Our
      mid-term results showed that appropriate enlargement of the pulmonary valve
      annulus preserved good RV function in patients with TOF.

PMID- 16281855
TI  - [Advantages of side-to-side anastomosis in the assessment and revision of
      coronary artery bypass grafting].
AB  - With the advent of drug eluting stents in percutaneous coronary intervention,
      required quality level of coronary artery bypass grafting (CABG) has been
      elevating. To obtain nearly perfect patency of bypass grafts, intraoperative
      assessment and repair of abnormal grafts are helpful. We report systematic
      revision and safe repair technique of arterial grafts in CABG. Side-to-side
      instead of commonly used end-to-side anastomosis of arterial grafts is the first
      step in this technique. When any abnormalities are noted in intraoperative
      flowmetry of a graft, the distal surgical clip is removed. Free flow of the graft
      is measured. A coronary probe is gently inserted into the graft and the coronary
      artery. Vasodilators can be injected into the graft if necessary. When direct
      revision of the anastomosis is indicated, the graft is cut longitudinally from
      the distal end up to just proximal to the anastomotic site. The shape of the
      anastomosis can be observed directly without removing sutures. When re
      anastomosis is not indicated, the distal remnant graft tissue is folded back and
      utilized as a patch. Thus the graft can be easily closed without narrowing.

PMID- 16281856
TI  - [Off-pump coronary artery bypasssurgery in patients with mitral regurgitation].
AB  - Introduction of off-pump coronary artery bypass grafting (off-pump CABG : OPCAB)
      makes it possible to shorten the bypass time and cardiac arrest time in patients
      with both ischemic heart disease and valvular disease. This may be beneficial in
      patients with poor cardiac function and renal dysfunction. However, it is unclear
      whether such patients can tolerate the changes of hemodynamics during vertical
      displacement of the heart. In 3 patients who had ischemic heart disease with non
      ischemic mitral regurgitation, we performed OPCAB prior to mitral valve plasty.
      The changes of mitral regurgitation observed by transesophageal echocardiography
      and several hemodynamic parameters were monitored as the heart was moved to
      various positions during OPCAB. When a heart positioner (Starfish) was used,
      hemodynamic deterioration was not observed, and there was also no aggravation of
      mitral regurgitation. Based on these results, we conclude that it may be possible
      to carry out OPCAB safely in patients with associated mitral regurgitation.

PMID- 16281857
TI  - [The use of fibrous wound dressing sheets made of carboxymethylcellulose natrium
      in the postoperative management of tracheostomy].
AB  - Postoperative management of tracheostomy is very important to reduce several
      complications such as abnormal granulation and subcutaneous abscess. One of the
      causes is the use of gauzes and a disinfectant because they induce the secondary
      wound injury and prevention of wound healing. We used a fibrous wound dressing,
      carboxymethylcellulose natrium sheet (Aquacel) on the postoperative management of
      tracheostomy for 5 patients. The sheets were very useful to absorb exudates
      including blood and to make suitable moist and clean surroundings in all
      patients.

PMID- 16281858
TI  - [Blalock-Taussig shunt and pulmonary artery angioplasty for isolated unilateral
      absence of the right pulmonary artery; report of a case].
AB  - A 7-month-old girl was referred to us for further examination of absence of the
      right pulmonary artery. She had no symptom at that time. Diagnosis was made by
      chest computed tomography (CT) and cardiac catheterization. Though the size of
      the right pulmonary artery was not apparent, right pulmonary vein wedge
      angiography revealed the distal portion of right pulmonary artery sufficient for
      surgical repair. But the distance between the pulmonary trunk and right pulmonary
      artery was too far to perform direct anastomosis, and some systemic collaterals
      had already been recognized. Pulmonary vasculature was also not inadequate.
      Therefore we planned a palliative procedure. At the age of 7 months, right
      modified Blalock-Tausig shunt using 5mm expand-polytetrafluoroethylene (ePTFE)
      tube and angioplasty of the distal portion of right pulmonary artery using
      autologous pericardium roll with Dacron mesh was performed. Postoperative course
      was uneventful. She has been followed up for 6 months after the palliation. In
      the near future the completion of the definitive repair will be considered.

PMID- 16281859
TI  - [Bentall operation for the annuloaortic ectasia which merged liver cirrhosis and
      pericarditis; report of a case].
AB  - We report a case of successful aortic root replacement using a stented
      bioprosthetic valved conduit and pericardiectomy in a patient with liver
      cirrhosis and constrictive pericarditis. A 72-year-old man treated for alcoholic
      liver cirrhosis was referred for the aortic regurgitation and dilatation of sinus
      of Valsalva. He underwent Bentall operation using a stented bioprosthetic valved
      conduit and pericardiectomy successfully. For patients whose anticoagulation is
      contraindicated, aortic root replacement using valved conduit with bioprosthesis
      is useful option. Concomitant pericardiectomy for constrictive pericarditis may
      provide better long-term results.

PMID- 16281860
TI  - [Severe tracheal compression resulting from atherosclerotic aortic arch aneurysm;
      report of a case].
AB  - A 70-year-old woman presented with severe respiratory insufficiency similar to an
      asthma attack. Computed tomography (CT) revealed an atherosclerotic aneurysm
      (maximum diameter 106 mm) on the aortic arch which resulted in a severe tracheal
      compression. We performed an aortic arch replacement. After the operation, we
      tried to manage breathing without a respirator twice without success. We then
      performed a tracheotomy on the 12th day after operation. The patient could
      breathe independently on the 19th day after the first operation. Peri-and
      postoperative respiratory management was difficult but the patient was discharged
      on the 86th day after operation without further complication.

PMID- 16281861
TI  - [Stanford type A aortic dissection with occlusion of the brachiocephalic artery;
      report of a case].
AB  - A 73-year-old female was referred to our hospital because of pain in the right
      upper extremity, left hemiparesis and syncope. Computed tomography (CT) of the
      head showed no active lesion, but chest CT showed Stanford type A aortic
      dissection with occlusion of the brachiocephalic artery. Carotid ultrasonography
      showed occlusion of the right common carotid artery. Emergent graft replacement
      of the ascending aorta and aortic arch was performed. The right common carotid
      artery was opened but no thrombus was found. In order to restore and maintain the
      cerebral circulation, the right carotid artery was cannulated. Postoperative head
      CT showed a small cerebral infarction of the right parietal lobe. Syncope did not
      recur and her hemiparesis was treated by rehabilitation. Cannulation of the
      carotid artery is useful for cases with occlusion of the brachiocephalic artery.

PMID- 16281863
TI  - [Intrapulmonary aberrant needle; report of a case].
AB  - Intrapulmonary aberrant needles are rarely encountered in clinical practice. An
      intrathoracic aberrant needle should be always surgically removed as soon as
      possible. We report a case of an intrapulmonary aberrant needle removed with
      video-assisted thorascopic surgery (VATS) and briefly review the literature. A 47
      year-old man referred to us for chest discomfort was found to have an
      intrapulmonary aberrant needle at the right middle lobe by chest X-ray and
      computed tomography (CT). We tried simple extraction under thoracoscopy, but a
      residual fragment was recognized by intraoperative X-ray after the removal of the
      needle from the surface of the lung. We searched for the residual fragment by
      real-time fluoroscopic examination. Partial resection was performed to remove the
      residual needle fragment at the right lower lobe. The postoperative course was
      uneventful and the man was discharged on the postoperative day 10. Intraoperative
      chest X-ray is always necessary before closing the chest to avoid leaving the
      residual fragments in the lung. The real-time fluoroscopy is useful to search for
      the residual fragment.

PMID- 16281862
TI  - [Traumatic aortic regurgitation complicating chronic bronchitis; report of a
      case].
AB  - A 61-year-old man with diabetes mellitus and chronic bronchitis was brought to
      the hospital after falling from a roof accidentally. He received blunt trauma to
      the left chest wall including left rib fractures, pneumothorax, hemothorax and a
      fracture of left scapula. After endotracheal intubation and chest drainage, he
      was transferred to the intensive care unit. Sixteen days later, congestive heart
      failure appeared. Echocardiography showed a severe aortic valve regurgitation
      with a prolapse of non-coronary cusp. Eight months after the injury, his heart
      failure deteriorated. He underwent aortic valve replacement with a mechanical
      prosthesis. Upon examining the aortic valve, we noted 2 perforations in the non
      coronary cusp of the aortic valve. Postoperative course was uneventful.

PMID- 16281864
TI  - [Ruptured lung abscess; report of a case].
AB  - We reported an extremely rare case of ruptured lung abscess. A 60-year-old male
      was admitted to our hospital with sudden loss of consciousness. Thoracocentesis
      demonstrated pneumopyothorax. Right middle and lower lobectomy for ruptured
      abscess was performed. The patient remains well with no recurrent lung abscess 2
      years postoperatively. This case emphasizes that ruptured lung abscess is a cause
      of pneumopyothorax.

PMID- 16281865
TI  - [Congenital cystic adenomatoid malformation detected by prenatal sonography;
      report of 2 cases].
AB  - We report 2 cases of congenital cystic adenomatoid malformation (CCAM) detected
      by prenatal sonography. The first CCAM was diagnosed by fetal sonography in a
      female fetus at 30 weeks' gestation. The infant was born at 37 weeks' gestation,
      with a body weight of 2,770 g. After birth, chest computed tomography (CT) showed
      a multicystic mass in the middle lobe of the lung. She remained asymptomatic
      until age 21 months, when she suffered pneumonia. Two months later, middle
      lobectomy was performed. The second CCAM was diagnosed by fetal sonography in a
      female fetus at 25 weeks' gestation. She was born at 39 weeks' gestation, with a
      body weight of 3,292 g. Four days after birth, CCAM type II was diagnosed by
      chest CT. The infant was asymptomatic, and left lower lobectomy was performed 11
      months after birth.

PMID- 16281867
TI  - [The Japan Contact Lens Society Guidelines for Contact Lens. History].

PMID- 16281866
TI  - [Yolk sac tumor of the anterior mediastinum and pulmonary metastases; report of a
      case].
AB  - A 31-year-old female was clinically diagnosed as having a anterior mediastinal
      yolk sac tumor because of the elevation of the AFP (17,500 ng/ml), a large mass
      lesion (9 x 5 cm) in the anterior mediastinum and bilateral lung metastases.
      After 4 courses of chemotherapy with cisplatin (CDDP), etoposide (VP-16) and
      bleomycin hydrochloride (BLM), the mediastinal mass reduced in size significantly
      and the serum AFP level reached within normal range. Fluorodeoxyglucose-positron
      emission tomography (FDG-PET) showed a weak uptake in the mediastinum,
      accordingly the operation was performed. The tumor was completely removed and
      there were no viable foci of the tumor in part of the tumor. After the operation,
      4 courses of chemotherapy with carboplatin (CBDCA), VP-16 and ifosfamide (IFM)
      were performed. She is alive without evidence of recurrence in 5 months after
      operation. It was noticed that the serum AFP is a useful indicator for determing
      the chance of operation after chemotherapy.

PMID- 16281868
TI  - [The Japan Contact Lens Society Guidelines for Contact Lens. The types of contact
      lenses].

PMID- 16281869
TI  - [The Japan Contact Lens Society Guidelines for Contact Lens. Contact lens care].

PMID- 16281870
TI  - [The Japan Contact Lens Society Guidelines for Contact Lens. Adaptation and
      selection of a contact lenses].

PMID- 16281871
TI  - [The Japan Contact Lens Society Guidelines for Contact Lens. Prescription of a
      contact lenses].

PMID- 16281872
TI  - [The Japan Contact Lens Society Guidelines for Contact Lens. Contact lens
      complications].

PMID- 16281874
TI  - [The Japan Contact Lens Society Guidelines for Contact Lens. Basic principles].

PMID- 16281873
TI  - [The Japan Contact Lens Society Guidelines for Contact Lens. Special contact lens
      prescription].

PMID- 16281875
TI  - [A review 24: blepharospasm and hemifacial spasm].

PMID- 16281876
TI  - [Germany DRGs in 2004--now it will be in earnest].

PMID- 16281877
TI  - [Anti-p200 pemphigoid--a new bullous autoimmune dermatosis].
AB  - Anti-p200 pemphigoid is an autoimmune skin disease characterized by tense
      blisters, subepidermal split formation, and mainly neutrophilic inflammatory
      infiltration of the dermal-epidermal junction (DEJ). Direct immunofluorescence
      microscopy of perilesional skin biopsies demonstrates linear deposits of IgG and
      C3 along the DEJ, while by indirect immunofluorescence microscopy on NaCI-split
      human skin, patients' IgG labels the dermal side. The antigenic target of the
      autoantibodies is a 200 kD protein (p200) of the lower lamina lucida that can be
      detected in human dermal extracts by immunoblotting. While p200 is thought to be
      important for cell-matrix adhesion, its exact identity is unknown. To date, the
      p200 autoantigen has been demonstrated to be distinct from bullous pemphigoid
      antigens 180 und 230, laminin 1, 5, and 6, alpha6beta4 integrin, and type VII
      collagen. Biochemical characterization of the p200 molecule revealed a
      noncollagenous N-glycosylated acidic protein with an isoelectric point of
      approximately 5.5. We provide an overview on pathogenesis, clinical features,
      diagnosis, and treatment of this unique autoimmune dermatosis.

PMID- 16281878
TI  - [G-DRG Version 2004: changes in view of dermatology].
AB  - In the year 2004 the obligatory introduction of the new hospital funding system
      based on a Diagnosis Related Groups (DRG) system will become reality for all
      German hospitals. After all fundamental items of the new G-DRG version were made
      generally known, the possible consequences had to be considered. The first
      mandatory German case-based lump sum catalogue differs importantly from the
      previous payment models and requires intensive study. Economic considerations
      will increasingly play a role in the daily routine of hospitals and influence
      treatment patterns. Therefore, comprehensive knowledge of basic principles of G
      DRG is essential. In the following aspects of the reimbursement system with
      special relevance to dermatology are reviewed in detail. Additionally, the
      revised classification system versions OPS-301 SGB V and ICD-10-GM 2004 and the
      German coding standards version 2004 must be appropriately applied for
      dermatologic purposes.

PMID- 16281879
TI  - [DRGs in dermatology: results of the DRG evaluation project of the German Society
      of Dermatology (DDG)].
AB  - SUMMARY BACKGROUND: The implementation of a DRG system in Germany--voluntarily
      since January 1st, 2003, and obligatory after January 1 st, 2004--has led to
      uncertainty, particularly in the hospitals. There are fears that current well
      accepted German diagnostic and therapeutic services may not be properly financed
      by the new system. In response, the German Dermatologic Society (DDG) in
      cooperation with the DRG Research Group of the University Hospital Muenster and
      the German Medical Association carried out a DRG evaluation project in order to
      investigate the medical and economic homogeneity of the case groups. PATIENTS AND
      METHODS: 19,403 dermatological cases from 19 hospitals--ten university hospitals
      and nine non-university hospitals-were collected over a period of four months and
      then evaluated with regard to their performance, length of stay and cost
      homogeneity. RESULTS: The data provided the background needed to indicate
      suspected potential deficiencies for mapping dermatology cases within the German
      DRG system. Based on the data 10 modifications were formulated and submitted to
      the InEK by the deadline of March 31st, 2003. CONCLUSIONS: The results of the DRG
      Evaluation Project show that the G-DRG-Variant Version 1.0 does not offer the
      necessary possibilities of differentiation to map the broad spectrum of various
      dermatology services in Germany.

PMID- 16281880
TI  - Low dose isotretinoin combined with tretinoin is effective to correct
      abnormalities of acne.
AB  - BACKGROUND: Isotretinoin is well known in the therapy of acne papulopustulosa and
      acne conglobata. No study has investigated the pathophysiological changes of the
      skin of acne patients, especially when low dose oral isotretinoin is given in
      combination with topical tretinoin. PATIENTS AND METHODS: 28 patients were
      treated for 6 months with oral isotretinoin. In the acne conglobata group (A-C)
      patients were treated with 10 mg (Group A) or 20 mg isotretinoin (Groups B, C) in
      combination with topical 0.05% tretinoin cream. Group C was treated the first 2
      weeks with 0.05% betamethasone valerate cream instead of tretinoin cream. In the
      acne papulopustulosa group, the patients received 0.5 mg isotretinoin/kg
      bodyweight and 0.05% tretinoin cream, either alone (Group E), or with oral
      methylprednisolone during induction (Group D). RESULTS: Acne conglobata--A
      reduction of inflammatory lesion by 87-94% and of non-inflammatory lesions by 81
      88% was achieved (Groups A-C). A reduction of sebaceous gland size by 35-58%,
      sebum production by 90-95%, follicular keratinization by 55-70% and
      Propionibacteria by 33-73% was seen (Groups B and C better than Group A). In
      Group A the amount of lipids was only reduced by 6%, in Group B by 35% and in
      Group C by 40%. Acne papulopustulosa--Sebum excretion rate and follicular
      keratinization were reduced in Group D by 89% and 50% respectively, with
      isotretinoin alone by 94% and 53%. The amount of lipids was reduced in Group D by
      40% and in Group E by 21%. CONCLUSIONS: Because of the efficacy and cost-benefit
      relationship of isotretinoin in the treatment of acne compared to other
      therapeutic approaches, further use low dose isotretinoin in the described
      settings seems to justified.

PMID- 16281881
TI  - [Larva migrans "saxoniae": larva migrans infection in Saxony].
AB  - A 38 year old woman from Dresden presented in September 2002, about four weeks
      after the Elbe River flooding with signs of cutaneous larva migrans on the back
      of her hand. There was no history of travel to tropical or subtropical regions in
      the last few years. Cryotherapy as well as systemic ivermectin (Stromectol)
      therapy were not successful in stopping progress of the lesions. Combination
      therapy with systemic ivermectin and topical tiabendazole (Lombristop) induced
      full remission. Cutaneous larva migrans normally occurs in German patients only
      after recent visits to tropical or subtropical regions. In our patient, however,
      it was most likely due to the unusual climatic conditions in the summer of 2002
      in the Elbe region: Heavy rainfalls and inundation by regional rivers soaked the
      ground, followed by a period of unusually hot and sunny weather.

PMID- 16281882
TI  - [Successful treatment of Stewart-Treves syndrome with liposomal doxorubicin].
AB  - The Stewart-Treves syndrome (STS) is a lymphedema-associated angiosarcoma which
      usually develops in female patients after mastectomy and axillary lymph node
      dissection. A 55-year old woman developed STS in her lymphedematous left arm
      seven years after breast-preserving surgery with axillary lymph node dissection
      and radiotherapy. Various therapies which have been employed are radiotherapy and
      isolated limb perfusion with cytostatic agents. Since our patient had a huge
      lesion with additional chest wall involvement, neither approach represented a
      good option. Radiological staging showed no evidence of further lesions or
      metastases. We started infusion therapy with liposomal doxorubicin (20 mg/m2 body
      surface) fort six cycles at regular intervals of 14 days. The patient tolerated
      the therapy well. Palmar-plantar erythrodysesthesia, a well-known side effect of
      doxorubicin, did develop. Because the disease was stable, the therapy interval
      was increased to six weeks after the 6th cycle. The patient has shown no
      recurrence for eight months. STS is a very rare variant of an angiosarcoma with
      poor prognosis. The case report shows that liposomal doxorubicin provides an
      effective therapeutic option.

PMID- 16281883
TI  - [Skin undesirable medication adverse reactions--legal compliance and procedures
      for reporting].

PMID- 16281884
TI  - [Crusty erosion of the capillitium as well as cheek and nose in an 88-year old
      man].

PMID- 16281885
TI  - [Standards in psychotherapeutic medicine for artificial diseases (ICD-10F.68.1)].

PMID- 16281886
TI  - Maximizing power and minimizing treatment failures in clinical trials.
AB  - BACKGROUND: Response-adaptive randomization procedures have a long history in the
      theoretical statistics literature over the past four decades. The main idea
      historically was to develop randomization procedures that place fewer patients on
      the inferior treatment. More recent research has changed the main focus to that
      of usual considerations in typical clinical trials: power, sample size, expected
      treatment failures, maintaining randomization, among others. METHODS: We describe
      response-adaptive randomization procedures for simple clinical trials comparing
      two binomial success probabilities, including the randomized play-the-winner
      rule, the drop-the-loser rule, and a modification of the doubly-adaptive biased
      coin design. We treat as our principal goal minimizing expected treatment
      failures while preserving power and randomization. Based on some recent
      theoretical literature, the basic guidelines for selecting an appropriate
      procedure include targeting optimal allocation, having small variability, and
      preserving randomization. We use simulation to compare power and expected
      treatment failures according to these guidelines. RESULTS: When the two
      treatments had high probabilities (> 0.5) of success, the randomized play-the
      winner rule was less powerful than complete randomization and the drop-the-loser
      rule by 1-3 percent with slightly larger expected number of treatment failures
      than the drop-the-loser rule. For all the success probabilities we examined, the
      drop-the-loser rule was within 1 percent of the power of complete randomization
      with a modest reduction of treatment failures. The doubly-adaptive biased coin
      design was as powerful or slightly more powerful than complete randomization in
      every case and expected treatment failures were always less, with modest
      reductions of the order of 0.3 percent to 8.3 percent. CONCLUSIONS: We conclude
      that the drop-the-loser rule and a modification of the doubly-adaptive biased
      coin design are the preferred procedures, and simulations show that these
      procedures yield a modest reduction in expected treatment failures while
      preserving power over complete randomization.

PMID- 16281887
TI  - Multiple-stage screening and mortality in the Multiple Risk Factor Intervention
      Trial.
AB  - BACKGROUND: During the design phase of a clinical trial, sample size estimates
      should take into account medical screening criteria, the 'healthy volunteer'
      effect, consequences of run-in phases, and secular trends in the event rate of
      interest. All of these have been shown to relate to subsequent event rates, and
      hence trial power to detect intervention effects. The Multiple Risk Factor
      Intervention Trial (MRFIT) used three successive screenings of 361 662 men to
      enroll 12 866; observed coronary heart disease (CHD) mortality after a mean of
      6.9 years was substantially lower than projected during design. We explore
      factors which may have contributed to these mortality differences and whether
      they persisted throughout follow-up. METHODS: Proportional hazards models were
      used to compare 25-year mortality according to trial eligibility, self
      exclusions, medical exclusions, and participation. RESULTS: After adjustment for
      baseline risk factors and age, there was higher mortality among men excluded for
      presence of disease [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.43
      1.61, for total; HR 1.92, CI 1.75-2.11, for CHD] compared to those not excluded
      which persisted throughout follow-up. Volunteers had lower total (HR 0.82, CI
      0.76-0.87) and CHD (HR 0.79, CI 0.70-0.88) mortality than those discontinuing
      participation. Men excluded with characteristics deemed likely to interfere with
      adherence had higher total (HR 1.19, CI 1.07-1.33) and non-cardiovascular disease
      (CVD) (HR 1.32, CI 1.14-1.53) mortality but no higher CVD (HR 1.04, CI 0.88-1.23)
      or CHD (HR 0.98, CI 0.80-1.20) mortality compared to those not excluded.
      Differences in mortality were stronger during the first five years, but declined
      only slightly over 25 years. CONCLUSIONS: 25-year mortality was significantly
      higher for non-volunteers and exclusions. Differences between observed and
      predicted six-year total mortality for trial participants were largely
      attributable to volunteers and exclusions, but there were additional differences
      for CHD mortality, which were likely due to downward secular trends. These
      results emphasize the importance of anticipating these factors during clinical
      trial design, even for trials of short duration.

PMID- 16281888
TI  - Issues in regulatory guidelines for data monitoring committees.
AB  - As clinical trials have emerged as the major research method for evaluating new
      interventions, the process for monitoring intervention safety and benefit has
      also evolved. The Data Monitoring Committee (DMC) has become the standard
      approach to implement this responsibility for many Phase III trials. Recent draft
      guidelines on the operation of DMCs by the Food and Drug Administration (FDA)
      have raised issues that need further clarification or discussion, especially for
      industry sponsored trials. These include, the time when DMCs are needed, the role
      of the independent statistician to support the DMC, and sponsor participation at
      DMC meetings. This paper provides an overview of these issues, based on the
      discussions at the January, 2003 workshop sponsored by Duke Clinical Research
      Institute.

PMID- 16281889
TI  - Equipoise: a case study of the views of clinicians involved in two neonatal
      trials.
AB  - BACKGROUND: It is considered to be a fundamental ethical premise of human
      experimentation, that it should be carried out only where the effects of an
      intervention are unclear. The point at which it is considered that there is
      insufficient scientific and medical evidence to clearly state the superiority of
      an intervention has been termed equipoise. This concept has been the subject of
      much recent impassioned debate but little empirical research about the views of
      people involved in recruitment to randomized controlled trials (RCTs), and none
      in the particularly emotive area of neonatal intensive care. METHODS: Thirty
      neonatologists recruiting into one or both of two neonatal RCTs in five centres
      in England were interviewed using a semi-structured schedule to explore their
      involvement in randomised trials. The interviews were tape-recorded and
      transcribed. Equipoise was one among a range of topics covered. Concepts relating
      to equipoise were identified by close reading of the entire interviews. Themes
      emerging from the data were noted in their contexts then discussed between the co
      authors. Interviewees also completed a brief questionnaire about their
      demographic background, and their experience of research and RCTs. RESULTS:
      Almost all the neonatologists used the concept of equipoise [using words and
      phrases such as uncertainty, lack of knowledge (or ignorance), strengths of
      views, and balancing of pros and cons] in their interview and, for most of them,
      equipoise seemed to be a useful term. They explored ideas about equipoise at the
      individual and community levels, and some linked equipoise with notions of the
      responsibility that should be exercised by the scientific and professional
      communities. They differed in the importance they gave to individual equipoise,
      and in how they reacted to threats to equipoise. Feelings of doubt about a trial
      and disturbed equipoise were more often expressed by more junior doctors.
      CONCLUSIONS: Our findings suggest that the concept of equipoise goes beyond the
      idea of uncertainty. In part this is because it includes the balancing of benefit
      and harm; this balancing is part of a professional obligation and requires
      engagement with 'expert' knowledge. Equipoise could therefore be seen as 'active'
      or 'responsible' uncertainty. Elucidation of this difficult concept may help to
      facilitate recruitment for both clinicians and parents in future trials and
      thereby help to find answers to important clinical questions.

PMID- 16281890
TI  - Personal reflections on lessons learned from randomized trials involving newborn
      infants from 1951 to 1967.

PMID- 16281891
TI  - [Nursing scholarship and nursing research--where is it headed?].

PMID- 16281892
TI  - ["Tied down"--the process of becoming bedridden through gradual local
      confinement].
AB  - To be bedridden is a common phenomenon in nursing. However, there is no solid
      base of knowledge on reasons, types, development of and coping with this
      situation. The concept of being bedridden is applied in an arbitrary manner and
      the state of being bedridden is far from being clearly defined. A literature
      review revealed that only pathophysiological effects of this state are
      sufficiently explained. The aim of this study was to gain knowledge of the
      development of being confined to bed. Thirty-two interviews with elderly,
      bedridden people (nineteen women, thirteen men) were conducted. They were asked
      about their perspective on and their experience of the development of being
      confined to bed. Half of the interviewees lived in a nursing home, the others
      were cared for at home. Data collection and analysis were performed by using a
      Grounded Theory approach as developed by Strauss and Corbin. "Gradual local
      fixation" was identified as the core category. Becoming bedridden is a slow
      process by which the person is increasingly confined to one location. This
      development is related to an increasing need for support and to negative
      consequences such as a pathology of immobility, narrowing of interests, and loss
      of time. These consequences again are responsible for a downward spiral
      development. This study reveals phases of development and a range of factors
      influencing them. Many of these factors arise from the person and his/her
      interactional behaviour in the circumstances, other influences are structural
      factors such as external pressure caused by time constraints of professional
      nursing services or unfavourable arrangements of furniture. A lot of factors of
      being confined to bed are changeable. Long periods of being bedridden can be
      prevented in many cases, if early warning signs are being recognized and
      preventive measures are taken in time.

PMID- 16281893
TI  - [Ready for antiretroviral therapy? Therapy decision making experiences of persons
      living with HIV].
AB  - Readiness for therapy of people living with HIV is of major importance in the
      process of antiretroviral decision making. This qualitative study is part of a
      prospective multicentre investigation describing readiness for antiretroviral
      therapy (ART) and decision making in HIV-infected patients. The qualitative
      results present the daily experiences of people living with HIV in the treatment
      decision making process related to starting or changing ART. Based on a critical
      hermeneutic research design, interviews with twelve persons have been conducted.
      Two main categories were generated: "dealing with oneself and others" and
      "understanding and being understood". They describe the dialectical process of
      decision making with a focus on interactions with others. This process includes
      four themes: illness beliefs, health perspectives, therapy beliefs, life
      perspectives. The findings of this study reveal that partnerships of health care
      providers with HIV-infected patients are necessary for treatment decisions.
      Moreover; it is of major importance for health care providers to include
      patients' experiences and expertise and to allow time for the different
      dialogues.

PMID- 16281894
TI  - [Urinary incontinence as a risk factor for pressure sores does not withstand a
      critical examination].
AB  - The association between urinary incontinence and pressure sores is put down to
      various causes. Most frequently urinary wet and following maceration of the skin
      are mentioned. However, it is possible that urinary incontinence is only an
      indicator for other risk factors or a measure of the need for care without any
      causal relation to pressure sores. There are hardly any controlled or randomised
      studies; this lack of scientific evidence is problematic. Based on a case-control
      study including data of 200 patients as well as on the existing models of
      explanation, the following study tries to examine critically the connections
      between pressure sores and urinary incontinence. Out of the patients in our study
      population 97.5 percent were incontinent. Different categories of the risk factor
      urinary incontinence and different dichotomisations have led to different
      statistical results. Statements concerning the connection between urinary
      incontinence and pressure sores have to be interpreted critically. The dependence
      of urinary incontinence on other risk factors such as patients' need for care or
      compliance suggests that the causal connection to pressure sores be not reduced
      to the influence of wetness. We advise to research connections between urinary
      incontinence and pressure sores in a methodologically appropriate setting.

PMID- 16281895
TI  - [Migration specific transitions and family care-giving].
AB  - This qualitative study focuses on care-giving among Russo-German re-settlers.
      Since the early '90s, Russo-Germans have been increasingly allowed to return to
      Germany. Up to now, the phenomenon of care-giving in this group was little known.
      The meaning of family care-giving within this particular group of immigrants can
      only be understood by investigating the foundations of care, the kind of care
      given, and the ways of providing care. Using the Grounded Theory method, four
      data sets of 81 interviews have been conducted and analysed in Russia and
      Germany. Care-giving among Russo-German re-settlers is part of a system of
      comprehensive family care and support stemming from a collectivistically oriented
      family concept. Family care is taken for granted and experienced as a must. On
      account of their biographic experiences and the experiences of immigration, the
      caring behaviour of Russo-German re-settlers is not necessarily congruent with
      the caring behaviour practised in Germany, let alone the caring behaviour of
      professional carers. This has an impact on the utilization of professional
      support. In order to provide helpful and meaningful support professional carers
      have to take into account the whole system of family carers and to avoid the
      separation of the family.

PMID- 16281896
TI  - [Nursing and self-help in the context of chronic illness and disability].
AB  - The promotion and maintenance of independence of chronically ill or handicapped
      people are particular objectives of professional nursing as well as coping in
      self-help groups. Accordingly, nursing and self-help may complement each other in
      the care for chronically ill or handicapped people. Evidence suggests that self
      help groups contribute to health related knowledge, mutual aid and social support
      as well as modifications of attitudes of the group members and their social
      environment. They disburden the primary social networks and families of the
      afflicted persons and reinforce the "intelligent" utilisation of the professional
      services of the health care system. Nevertheless, the integration of self-help
      initiatives in the health care system is precarious. The co-operation between
      self-help groups and the professional health care system is characterised by an
      imbalance between medical laymen and experts. Nursing staff in hospitals are
      important co-operation partners and contact persons for self-help groups. To
      understand better the effects of self-help groups, longitudinal studies with non
      randomised comparison groups are needed. Further research should address the
      questions, how larger proportions of the population can be involved in self-help
      activities and how the relevance of self-help differs in various diagnosis
      groups. Research in the area of self-help is fragmented; research promotion and
      co-ordination in this area appear to be necessary.

PMID- 16281897
TI  - [Effects of cost saving strategies and staffing levels on patient and nurse
      outcomes. A literature review].
AB  - The effects of cost saving strategies and changes in staffing levels and skill
      mix in the inpatient care setting on patient and nurse outcomes have not yet been
      examined in Switzerland. In 2002 the Swiss Federal Office of Health mandated the
      Institute of Nursing Science at the University of Basel to conduct a literature
      review to examine the evidence available on this topic. The literature research
      and analysis cover the period from 1991 to 2003. Sixty publications out of a
      total of 260 reviewed abstracts were included and analyzed. The results show that
      in the inpatient care settings in Switzerland as well as in other countries
      positions for registered nurses have been reduced and/or the qualification and
      skill mix in care teams have been downgraded. Given the present health care
      situation where the intensity and complexity of caring for hospitalized patients
      is increasing, an imbalance occurs between the need for high quality care and the
      possibilities to offer this care. This affects patients' and nurses outcomes. The
      international results show a significant relationship between lower staffing
      levels and skill mix in care teams and higher complication, "failure-to-rescue",
      and mortality rates in patients, as well as a lower job satisfaction, and higher
      fluctuation, burnout and work-related injury rates in nursing personnel. Thus,
      nursing care within hospitals represents not only a cost factor but also an
      important quality factor which is essential in order to be able to realize good
      patient's outcomes.

PMID- 16281905
TI  - Phenotypic variability in human prion diseases.
AB  - Human prion diseases are rare neurodegenerative disorders that can occur as
      sporadic, familial or acquired disorders. Within each of these categories there
      is a wide range of phenotypic variation that is not encountered in other
      neurodegenerative disorders. The identification of the prion protein and its key
      role in the pathogenesis of this diverse group of diseases has allowed a fuller
      understanding of factors that influence disease phenotype. In particular, the
      naturally occurring polymorphism at codon 129 in the prion protein gene has a
      major influence on the disease phenotype in sporadic, familial and acquired prion
      diseases, although the underlying mechanisms remain unclear. Recent technical
      advances have improved our ability to study the isoforms of the abnormal prion
      protein in the brain and in other tissues. This has lead to the concept of
      molecular strain typing, in which different isoforms of the prion protein are
      proposed to correspond to individual strains of the transmissible agent, each
      with specific biological properties. In sporadic Creutzfeldt-Jakob disease there
      are at least six major combinations of codon 129 genotype and prion protein
      isotype, which appear to relate to distinctive clinical subgroups of this
      disease. However, these relationships are proving to be more complex than first
      considered, particularly in cases with more than a single prion protein isotype
      in the brain. Further work is required to clarify these relationships and to
      explain the mechanism of neuropathological targeting of specific brain regions,
      which accounts for the diversity of clinical features within human prion
      diseases.

PMID- 16281906
TI  - Mcm2 labelling of balloon cells in focal cortical dysplasia.
AB  - Balloon cells (BC) are the prominent and defining cellular component of type IIB
      Focal Cortical Dysplasia (FCD), a common cause of focal epilepsy in patients
      undergoing surgical treatment. BC are considered immature cells of uncommitted
      cellular differentiation having immunophenotypical characteristics of both
      neurones and glia. They are often located in the lower cortical layers and white
      matter underlying the dysplastic cortex, suggesting migratory arrest during
      development. We investigated the proliferative potential of BC in 15 cases of FCD
      from patients with a wide range of ages using immunohistochemistry for Mcm2 (mini
      chromosome maintenance protein) and Ki67. In the majority of cases, BC showed
      Mcm2 nuclear positivity. In addition, cells with intermediate neuronal-glial
      characteristics were labelled whilst the dysmorphic or hypertrophic pyramidal
      neuronal components of FCD were not. Ki67 labelled only occasional BC. These
      findings support the view that BC cells represent a pool of less differentiated
      glial cells with proliferative capacity which may have potential for delayed
      neuronal differentiation. Furthermore, as Mcm2 specifically identifies BC
      populations, this marker may be of diagnostic value in the subtyping of FCD
      lesions in patients with epilepsy.

PMID- 16281907
TI  - Cerebral amyloid angiopathy in a 95+ cohort: complement activation and
      apolipoprotein E (ApoE) genotype.
AB  - There is growing evidence that in Alzheimer's disease (AD) amyloid beta-protein
      (Abeta) triggers a chronic inflammatory reaction in cerebral amyloid plaques,
      including complement proteins. Abeta also accumulates cerebrovascularly in age-
      and AD-associated cerebral amyloid angiopathy (CAA). We investigated complement
      proteins in CAA in a population-based series using histological and
      immunohistochemical staining methods. The 74 subjects, aged 95 years or more, had
      undergone clinical neurological examination and apolipoprotein E (ApoE)
      genotyping. The brains had been studied for AD post-mortem, allowing us to relate
      the histopathological findings to clinical and genetic conditions. CAA with
      congophilic amyloid was found in 36/74 individuals (48.6%). The vascular amyloid
      deposits immunoreacted with antibodies to Abeta and complements 3d (C3d) and 9
      (C9). The positivity in complement stains increased with growing severity of CAA
      (P = 0.001). The presence of CAA associated with ApoE epsilon4 (P = 0.0005) and
      overrepresentation of epsilon4 among those with moderate or severe vs. mild CAA
      (P = 0.03) was demonstrated. The presence of CAA associated with dementia (P =
      0.01), which was contributed by both epsilon4+ (P = 0.02) and epsilon4- (P =
      0.06) subjects. Our study shows that complement proteins are deposited in the
      affected vessels in Abeta-associated CAA. They may solely represent the cerebral
      Abeta- burden associated to inflammatory stimuli, or signal a contribution in the
      clearance of cerebral Abeta, thereby contributing to the events associated with
      evolution of clinical dementia. Our results demonstrate a strong association
      between CAA and ApoE epsilon4 as well as dementia and suggest that the
      contribution of CAA to dementia is largely independent of ApoE epsilon4.

PMID- 16281908
TI  - p75NTR independent oligodendrocyte death in cuprizone-induced demyelination in
      C57BL/6 mice.
AB  - Feeding C57Bl/6 J mice the copper chelator cuprizone leads to selective apoptosis
      of mature oligodendrocytes and concomitant demyelination predominantly in the
      corpus callosum. The process of oligodendrocyte apoptosis in this animal model
      for multiple sclerosis (MS) involves early microglial activation, but no
      infiltration of T-lymphocytes. Therefore, this model could mimic early stages of
      oligodendrocyte degeneration Affected oligodendrocytes express the common
      neurotrophin receptor, p75(NTR), a 'stress-receptor' which under certain
      circumstances can induce apoptosis. Only affected oligodendrocytes in MS lesions
      and MS animal models express this receptor. In order to study the significance of
      p75(NTR) in the fate of oligodendrocytes, we have exposed wild-type as well as
      p75(NTR)-knockout mice to a 0.2% (w/w) cuprizone diet and performed a comparative
      immunohistochemical analysis of the corpus callosum at various time points.
      Surprisingly, our results show that the absence of p75(NTR) did not alter
      cuprizone-induced oligodendrocyte death (and subsequent de- or remyelination).
      Apparently, intracellular apoptosis pathways in adult oligodendrocytes do not
      require p75(NTR) activated signal transduction in the absence of T-lymphocytes
      and T-lymphocyte derived cytokines.

PMID- 16281909
TI  - Effects of short-term hypoxia on neuroglobin levels and localization in mouse
      brain tissues.
AB  - Nerve cells are highly susceptible to ischemic and hypoxic injuries. The
      neuroglobin (Ngb), found in vertebrate nerve cells, has been suggested to protect
      nerve cells from ischemic episodes by a yet unknown mechanism. However,
      contradicting reports exist regarding localization and up-regulation of Ngb in
      response to hypoxia. The aim of the present study was to probe the distribution
      of Ngb proteins in mouse brain and retina by immunohistochemistry, and to
      quantify the levels of Ngb mRNA by reverse-transcription-polymerase chain
      reaction (RT-PCR) after short-term (2 h) exposure to 7.6% oxygen. We found Ngb to
      be present throughout the neocortex, most abundantly in the perirhinal,
      entorhinal and temporal cortical areas, the thalamus and hypothalamus, the
      choroid plexus, the olfactory bulb and the cranial nerve nuclei in the brainstem.
      Intense staining was observed in the mesencephalic central grey area and the
      Purkinje cells. Two-hour hypoxic exposure caused no detectable changes in
      staining intensity or spatial distribution of Ngb neither in the Purkinje cells
      nor in any other brain areas observed. The RT-PCR data supported the lack of
      differences in brain Ngb levels between normal and oxygen-deprived animals. In
      the retina, Ngb localization by immunohistochemistry was confined to the inner
      segments of the photoreceptors, the plexiform layers and the ganglion cells.
      Short-termed hypoxia did not change retinal Ngb levels as assessed by both
      techniques. The lack of Ngb up-regulation in the brain is consistent with results
      from previous long-term hypoxic experiments, suggesting that Ngb is not regulated
      by pure hypoxia in vivo.

PMID- 16281910
TI  - Cellular and reticular variants of haemangioblastoma revisited: a
      clinicopathologic study of 88 cases.
AB  - The presence of histological variants of haemangioblastoma is well established,
      but data on the prognostic implications of histological subtyping are missing. We
      thus characterized clinical factors associated with histological subtypes, that
      is, of the cellular and reticular variant of haemangioblastoma, in a series of 88
      consecutive primary haemangioblastomas of the central nervous system. Ten
      haemangioblastomas were classified as 'cellular' according to Cushing and Bailey.
      As compared to the more common 'reticular' variant (n = 78), the proportion of
      tumours containing glial fibrillary acidic protein-positive tumour cells (80% vs.
      7%), as well as median Ki67 (MIB1) proliferation indices [4% (quartiles: 1-8%)
      vs. < 1% (<1-2%)], was significantly higher in cellular haemangioblastomas (P <
      0.01). Recurrences were more frequent in the cellular variant [2/8 (25%) vs. 4/51
      (8%)]. Kaplan-Meier analysis confirmed a significantly higher probability of
      recurrence in the cellular variant (Log-Rank test P < 0.01). Cox regression
      analysis not only confirmed the well established association of von Hippel-Lindau
      disease with tumour recurrence (P < 0.01), but also revealed an independent
      effect of histological subtype on the probability of recurrence (P < 0.05),
      whereas no significant influence of age, sex or tumour location was observed. To
      conclude, the results from this retrospective study suggest that histological
      subtyping of haemangioblastomas has prognostic implications and might contribute
      to identify patients at risk for recurrence.

PMID- 16281911
TI  - Contributors to white matter damage in the frontal lobe in Alzheimer's disease.
AB  - Abnormalities of cerebral white matter are present in a majority of patients with
      Alzheimer's disease (AD) and probably contribute to motor dysfunction and
      cognitive impairment. The white matter abnormalities are usually attributed to
      degenerative vascular disease and cerebral amyloid angiopathy (CAA) but the
      evidence is scanty or inconclusive. In the present study we examined sections of
      frontal lobe from 125 autopsy-confirmed cases of AD and assessed the relationship
      of degenerative large and small vessel disease, CAA, parenchymal Abeta load and
      APOE genotype, to several objective measures of white matter damage: extent of
      immunolabelling for glial fibrillary acidic protein (GFAP), axonal accumulation
      of amyloid precursor protein (APP), axon density in superficial and deep white
      matter, and intensity of staining for myelin. We found no association between
      atherosclerosis, arteriolosclerosis, CAA or APOE genotype and white matter
      damage. However, labelling of white matter for GFAP correlated strongly with the
      parenchymal Abeta load (P = 0.0003) and with APP accumulation (P = 0.008). Our
      findings suggest that severity of frontal white matter damage in AD is closely
      related to parenchymal Abeta load and that in most cases the contribution of
      degenerative vascular disease, CAA and APOE is relatively minor.

PMID- 16281912
TI  - Subarachnoid injection of Microfil reveals connections between cerebrospinal
      fluid and nasal lymphatics in the non-human primate.
AB  - Based on quantitative and qualitative studies in a variety of mammalian species,
      it would appear that a significant portion of cerebrospinal fluid (CSF) drainage
      is associated with transport along cranial and spinal nerves with absorption
      taking place into lymphatic vessels external to the central nervous system. CSF
      appears to convect primarily through the cribriform plate into lymphatics
      associated with the submucosa of the olfactory and respiratory epithelium.
      However, the significance of this pathway for CSF absorption in primates has
      never been established unequivocally. In past studies, we infused Microfil into
      the subarachnoid compartment of numerous species to visualize CSF transport
      pathways. The success of this method encouraged us to use a similar approach in
      the non-human primate. Yellow Microfil was injected post mortem into the cisterna
      magna of 6 years old Barbados green monkeys (Cercopithecus aethiops sabeus, n =
      6). Macroscopic and microscopic examination revealed that Microfil was (1)
      distributed throughout the subarachnoid compartment, (2) located in the
      perineurial spaces associated with the fila olfactoria, (3) present within the
      olfactory submucosa, and (4) situated within an extensive network of lymphatic
      vessels in the nasal submucosa, nasal septum and turbinate tissues. We conclude
      that the Microfil distribution patterns in the monkey were very similar to those
      observed in many other species suggesting that significant nasal lymphatic uptake
      of CSF occurs in the non-human primate.

PMID- 16281913
TI  - Primary intracranial myopericytoma: report of three cases and review of the
      literature.
AB  - Myopericytoma is a benign tumour generally arising in the subcutaneous and
      superficial soft tissues of the extremities. Very few cases have been reported in
      other locations and intracranial examples are exceptional. We now report on three
      cases of primary intracranial myopericytoma and review the literature on that
      rare entity. The patients were women in their fifties who presented with
      decreased visual acuity in two cases and raised intracranial pressure in one
      case. The tumour involved, respectively, the anterior cranial fossa, the orbital
      apex and the pineal region. Gross total resection was achieved in all three
      cases. Histological analysis revealed oval-to-spindle shaped myoid-appearing
      cells with a striking tendency for concentric perivascular growth. The lesional
      cells showed apparent differentiation towards perivascular myoid cells as
      witnessed by smooth muscle actin expression. In one case, an epithelioid
      differentiation was also present. None of the patients received adjuvant therapy.
      One patient died of unrelated causes 6 months after surgery. The other two are
      alive and well at 9 and 12 month follow-up respectively. Myopericytoma is a
      recently described neoplasm, and it is likely that reappraisal of intracranial
      haemangiopericytoma with which it shares many histopathologic features will lead
      to more case reports of primary intracranial myopericytoma.

PMID- 16281914
TI  - Co-expression/co-location of S100 proteins (S100B, S100A1 and S100A2) and protein
      kinase C (PKC-beta, -eta and -zeta) in a rat model of cerebral basilar artery
      vasospasm.
AB  - OBJECT: The cellular events leading to cerebral vasospasm after subarachnoid
      haemorrhages (SAH) involve a number of members of the protein kinase C (PKC)
      family. However, whereas calcium is thought to play a number of major roles in
      the pathophysiology of SAH, a number of PKCs function independently of calcium.
      We recently emphasized the potential role of the calcium-binding S100 proteins in
      a 'double haemorrhage' rat model of SAH-induced vasospasm. A number of S100
      proteins are known to interfere directly with PKC, or indirectly with PKC
      substrates. We therefore investigated whether specific S100 proteins and PKCs are
      co-expressed/co-located in a rat model of SAH-induced vasospasm. METHODS AND
      RESULTS: SAH-induced vasospasm in rats (by means of a double cisternal injection
      of autologous blood from a rat femoral artery) distinctly modified the expression
      levels of calcium-dependent PKC-alpha and PKC-beta and calcium-independent PKC
      eta and PKC-zeta in endothelial and smooth-muscle cells. The RNA levels of these
      four PKC isotypes were determined by quantitative RT-PCR. The present study
      reveals that, in endothelial cells, the S100B expression/location correlate well
      with those of PKC-eta, and those of S100A1 with PKC-beta. In smooth-muscle cells
      S100A2 expression/location correlate with those of PKC-eta, and those of S100B
      with PKC-zeta. CONCLUSION: The present data argue in favour of a joint action of
      the S100 protein network and the PKC signalling pathway during cerebral
      vasospasm.

PMID- 16281916
TI  - Iatrogenic vertebral artery injury.
AB  - Iatrogenic vertebral artery injury (VAI) results from various diagnostic and
      therapeutic procedures. The objective of this article is to provide an update on
      the mechanism of injury and management of this potentially devastating
      complication. A literature search was conducted using PubMed. The iatrogenic VAIs
      were categorized according to each diagnostic or therapeutic procedure
      responsible for the injury, i.e., central venous catheterization, cervical spine
      surgery, chiropractic manipulation, diagnostic cerebral angiography, percutaneous
      nerve block, and radiation therapy. The incidence, mechanisms of injury, and
      reparative procedures were discussed for each type of procedure. The type of VAI
      depends largely on the type of procedure. Laceration was the dominant type of
      acute injury in central venous catheterization and cervical spine surgery.
      Arteriovenous fistulae and pseudoaneurysms were the delayed complications.
      Arterial dissection was the dominant injury type in chiropractic manipulation and
      diagnostic cerebral angiography. Inadvertent arterial injection caused seizures
      or stroke in percutaneous nerve block. Radiation therapy was responsible for
      endothelial injury which in turn resulted in delayed stenosis and occlusion of
      the vertebral artery (VA). The proximal VA was the most vulnerable portion of the
      artery. Although iatrogenic VAIs are rare, they may actually be more prevalent
      than had previously been thought. Diagnosis of iatrogenic VAI may not always be
      easy because of its rarity and deep location, and a high level of suspicion is
      necessary for its early detection. A precise knowledge of the surgical anatomy of
      the VA is essential prior to each procedure to prevent its iatrogenic injury.

PMID- 16281917
TI  - Apnea testing for the diagnosis of brain death.
AB  - OBJECTIVES: A review is given on various methods, preconditions and pitfalls of
      apnea testing for the diagnosis of brain death. MATERIALS AND METHODS: An
      extensive medical data base search was implemented by information gathered from
      books and our own experience with more than 2000 apnea tests. RESULTS: While
      testing for apnea (AT) is considered indispensable worldwide, recommendations and
      handling differ. Rather than relying on elapsed time, a specific target value for
      the partial arterial pressure of carbon dioxide (PaCO2) should be aimed at being
      the maximum physiological stimulus for respiration. Methodological points are
      elaborated upon in detail for apneic oxygenation and hypoventilation. CONCLUSION:
      AT is an indispensable element of diagnosing brain death. Although with proper
      handling and adequate precautions AT is safe, it should be performed as a last
      resort. An international agreement on target values for the PaCO2 is desirable.

PMID- 16281918
TI  - Prognosis of epilepsy in a community-based study: 8 years of follow-up in an
      Argentine community.
AB  - OBJECTIVE: To assess the prognosis of epilepsy, the possibility of achieving
      remission of seizures, in patients who were identified in a population-based
      study carried out in Junin, a city of about 70,000 inhabitants in Buenos Aires
      Province, Argentina. On January 1, 1991 (prevalence day), 106 people had
      epilepsy, including 64 (60%) with the condition active. METHODS: Eight years
      later, we revisited the patients identified in the prevalence study. We analyzed
      risk factors in relation to remission of seizures. We also confirmed the specific
      cause of death. RESULTS: Ninety-six patients were revisited (10 were completely
      lost to follow-up). We divided them into two groups: the group in terminal
      remission (defined as a seizure-free period that extended from prevalence day
      until the visit day in 1998) which included 64 people (66.7%), and the group of
      those who continued to have seizures which included 32 (33.3%) patients, of whom
      eight (25%) died. The overall standardized mortality ratio was 2.45; the rate was
      two and a half times that of the general national population. CONCLUSION: The
      better prognosis was observed in the group with generalized idiopathic epilepsy
      syndrome. Patients with epilepsy secondary to underlying structural causes had
      the worst prognosis, with higher mortality.

PMID- 16281919
TI  - An evaluation of gender, body mass index, wrist circumference and wrist ratio as
      independent risk factors for carpal tunnel syndrome.
AB  - OBJECTIVES: The aim of this study was to evaluate the role of gender, body mass
      index (BMI), wrist ratio (WR) and wrist circumference as independent risk factors
      for carpal tunnel syndrome (CTS) and to analyze the strength of association of
      these factors. METHODS: We have undertaken a case-control study in 128 CTS
      patients and 109 controls. Based on clinical and electrophysiologic criteria, 109
      female and 19 male CTS patients as well as 62 female and 47 male control subjects
      were selected from patients and their relatives referred to our hospital. In
      total, 179 hands with CTS in three groups of severity (mild, moderate and severe)
      were examined. Height, weight, BMI, wrist width, depth, circumference and ratio
      were measured in all patients and control group. Mean values of different risk
      factors for CTS group and controls were measured. A logistic regression analysis
      was conducted to evaluate odds ratio of different risk factors. RESULTS: The mean
      values for BMI and WR were greater in CTS patients than in the subject group.
      Thirty-four, 89 and 57 patients had mild, moderate and severe CTS, respectively.
      Mean age, BMI, wrist circumference and ratio were not statistically significant
      in the three groups. Female gender, increased BMI and increased WR had odds ratio
      of 9.95, 1.75 and 1.12, respectively. CONCLUSION: Our study confirms that female
      gender, obesity and square wrists are independent risk factors for CTS.

PMID- 16281920
TI  - 99mTc-TRODAT-1 SPECT study in early Parkinson's disease and essential tremor.
AB  - OBJECTIVE: The clinical differentiation between early Parkinson's disease (PD)
      and essential tremor (ET) could be difficult, therefore, the aim of this study
      was to investigate 99mTc-TRODAT-1 SPECT as an applicable tool in this field.
      METHODS: 99mTc-TRODAT-1 single photon emission computed tomography (SPECT) was
      performed in 10 healthy volunteers, 27 patients with idiopathic PD (Hoehn and
      Yahr 1-1.5) and 12 patients with ET. The ratio of striatal (99m)Tc-TRODAT-1
      binding was calculated as the index of (striatum - occipital cortex)/occipital
      cortex. RESULTS: Compared with the striatal 99mTc-TRODAT-1 uptake in the ET group
      (0.49 +/- 0.07) or healthy controls (0.54 +/- 0.18), there was a significant
      decrease in the bilateral striatums of early PD, with a greater reduction in the
      contralateral striatum (0.27 +/- 0.08) than ipsilateral one (0.36 +/- 0.10, P <
      0.01). Its sensitivity and specificity of differentiating early PD from ET was
      96.4% and 91.7% respectively. CONCLUSION: 99mTc-TRODAT-1 SPECT can detect the
      dysfunction of nigrostriatal system in patients with early PD and provided a
      feasible tool to help differentiate early PD from ET.

PMID- 16281921
TI  - The influence of cerebrovascular risk factors on incident dementia in patients
      with Parkinson's disease.
AB  - OBJECTIVE: To examine if risk factors for cerebrovascular disease would increase
      the risk for dementia in patients with Parkinson's disease (PD). METHODS: Non
      demented patients were recruited from an epidemiological study of PD in the
      county of Rogaland, Norway. PD and dementia were diagnosed according to strict
      diagnostic criteria. Established cerebrovascular risk factors were recorded at
      baseline, and their influence on incident dementia was assessed 4 years later
      using logistic regression analysis. RESULTS: A total of 171 non-demented PD
      patients constituted the at-risk population. Seventy-two (55%) had at least one
      cerebrovascular risk factor. A total of 130 subjects (96% of survivors) completed
      the follow-up examination. Forty-three (33%) new cases of dementia were found.
      Twenty-five of the 72 (35%) patients with and 18 of the 58 (31%) subjects without
      any risk factor developed dementia (ns). A significant association with dementia
      was found for a diagnosis of heart failure in the univariate analyses. However,
      in the logistic regression analysis none of the cerebrovascular risk factors were
      significantly associated with incident dementia. CONCLUSIONS: In this large and
      representative cohort of patients with PD cerebrovascular risk factors were not
      associated with incident dementia, indicating that the disease-related
      degenerative brain changes are the main causes of dementia in PD.

PMID- 16281922
TI  - HLA class II and response to interferon-beta in multiple sclerosis.
AB  - OBJECTIVE: To study the relationship between human leucocyte antigen (HLA)
      genotype and clinical response to interferon-beta (IFN-beta). METHODS: We
      analysed the HLA class II genotypes of 96 multiple sclerosis (MS) patients
      treated with IFN-beta. The patients were classified as responders or non
      responders according to clinical criteria: one or more relapses or a sustained
      increase after 1 year treatment compared with the year prior to IFN-beta therapy
      of > or = 0.5 points on the Expanded Disability Status Scale (EDSS). RESULTS:
      There were 66 (69%) responders and 30 (31%) non-responders. Baseline clinical
      characteristics were similar. We found no association between HLA class II
      alleles and clinical response to IFN-beta. CONCLUSIONS: HLA genotype does not
      appear to influence the clinical response to IFN-beta in MS patients.

PMID- 16281923
TI  - Presence of Epstein-Barr virus and human herpesvirus 6B DNA in multiple sclerosis
      patients: associations with disease activity.
AB  - OBJECTIVE: To assess the presence of Epstein-Barr virus (EBV) and human
      herpesvirus 6B (HHV-6B) DNA in saliva and plasma from multiple sclerosis (MS)
      patients enrolled in a randomized, double-blind, placebo-controlled valacyclovir
      treatment study. METHODS: DNA was prepared following ultracentrifugation of
      saliva and plasma. EBV and HHV-6B DNAs were determined by real-time polymerase
      chain reaction. RESULTS: EBV and HHV-6B DNAs were detected in 41% and 65% of
      saliva samples, respectively. In patients treated with valacyclovir, the
      percentage of saliva samples with EBV was significantly reduced (9%; P =
      0.000017), whereas the frequency of HHV-6B positive samples was unchanged (57%; P
      = 0.38). Longitudinal studies demonstrated a time-dependent reduction in the
      frequency of saliva samples containing EBV following valacyclovir treatment. In
      contrast, plasma contained EBV and HHV-6B DNAs in 17% and 25% of the samples,
      respectively, and these numbers were not significantly reduced following
      valacylovir treatment (13% and 16%, respectively), nor were they different from
      those of healthy controls (6% and 39%, respectively). Patients with high disease
      activity had a significantly higher frequency of EBV (P = 0.018) and HHV-6B (P =
      0.023) positive samples than did patients with low disease activity. The presence
      of EBV and HHV-6B was strongly correlated in plasma (P < 0.00000001), but not in
      saliva (P = 0.41). CONCLUSION: MS patients express EBV and HHV-6B in both saliva
      and plasma, but only the expression of EBV in saliva is significantly reduced
      following valacyclovir treatment. Although EBV and HHV-6B DNAs can be detected in
      plasma from healthy individuals, the co-expression of both these viruses in MS
      patients is highly significant and further associated with clinical activity. The
      observations of viral DNA in plasma are consistent with an underlying immunologic
      defect in MS.

PMID- 16281924
TI  - Measurement of autonomic dysregulation in multiple sclerosis.
AB  - OBJECTIVE: Patients with definite multiple sclerosis (MS) were tested for
      autonomic nervous system (ANS) dysfunction using clinical symptomatology criteria
      and non-invasive laboratory testing. Exactly 45.45% of patients exhibited
      subjective symptoms of autonomic dysfunction and 42.42% of patients had abnormal
      laboratory tests results. METHODS: The sympathetic ANS tests were abnormal in
      30.3% of MS patients and the parasympathetic ANS tests were abnormal in 18.18% of
      MS patients. The most sensitive test for the presence of autonomic dysfunction
      was the sympathetic skin response. CONCLUSION: Autonomic dysfunction was often
      subclinical and we conclude that it is preferable to combine several tests for a
      more thorough and accurate evaluation of the ANS impairment in MS.

PMID- 16281925
TI  - Comparison of different screening tests for detecting diabetic foot neuropathy.
AB  - INTRODUCTION: Regarding the major role of sensory neuropathy in diabetic foot
      ulcers, the use of an appropriate screening test for early detection of this
      neuropathy has a crucial role in the management of diabetic foot disorders. As
      there were no previous studies that performed all screening tests in the same
      group of patients, we performed all tests in a single group of diabetic patients
      and compared them to find out the possible differences between the results.
      METHODS: A total of 142 diabetic outpatients at Shariati Teaching Hospital were
      chosen by systematic randomized selection. Different screening tests for
      detecting neuropathy in diabetic foot such as symptom and sign scores, Michigan
      Neuropathy Disability Score (MNDS), and testing by a monofilament were performed
      for each patient. RESULTS: According to the neuropathy symptom score, 54.9% of
      the patients were neuropathic, their score was higher than 5, and by neuropathy
      sign score, 10.1% were neuropathic with a score higher than 6. Regarding MNDS,
      42.7% of the subjects were neuropathic, with a score higher than 3. Finally,
      23.9% were unable to sense at least one point in the monofilament examination.
      CONCLUSIONS: There were obvious differences between the results of different
      methods in our study. However, there were significant correlations between them,
      except between sign and symptom score methods. For determining the most reliable
      screening test, further studies are needed to compare these methods with a gold
      standard test and reveal the specificity and sensitivity of these tests.

PMID- 16281926
TI  - Postural stability before and after hyperbaric oxygen treatment.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of hyperbaric
      oxygenation (HBO) on postural stability in healthy volunteers. The study was
      performed in accordance with treatment protocols for divers' decompression
      sickness and carbon monoxide poisoning. METHODS: Twenty-one healthy male divers,
      aged 31 +/- 6.88 years (mean +/- SD), were tested with quantitative Romberg's
      test before and after HBO (90 min in a pressure chamber at an ambient pressure of
      253 kPa, approximately 15 m of sea water, breathing pure oxygen). The
      quantitative Romberg's test is a calculation of the average sway for 50 s.
      RESULTS: No difference was found between sway before and after the HBO (P <
      0.05), i.e. we were unable to show that the results of quantitative Romberg's
      test are affected by HBO. Thus, the quantitative Romberg's test may be a valuable
      tool in evaluating patients with decompressions sickness, carbon monoxide
      intoxication and other neurological diseases normally treated with HBO.

PMID- 16281927
TI  - Frequent association of multiple sclerosis with varicella and zoster.
AB  - BACKGROUND: A possible association of multiple sclerosis (MS) with viral diseases
      has been postulated; in previous studies we have found that in Mexican mestizos
      the antecedent of varicella during childhood represents a risk factor for the
      development of MS during adulthood. AIM: We conducted a retrospective search for
      varicella and zoster infections associated with the development of MS. METHODS
      AND RESULTS: In a cohort of 82 consecutive patients with MS we found six cases,
      four of varicella and two of zoster, that were concurrent with the development or
      the progress of MS. CONCLUSIONS: The association of these pathologies is higher
      than expected and suggests a possible etiological relationship of the varicella
      zoster virus with MS.

PMID- 16281928
TI  - Response to: 'Clinical characteristics of patients with ischemic ocular nerve
      palsies and lacunar brain infarcts--a retrospective comparative study'.

PMID- 16281930
TI  - Interdigitating dendritic cell sarcoma/tumour of the tonsil.

PMID- 16281931
TI  - Mast cell leukaemia.

PMID- 16281932
TI  - The interactions between inflammation and coagulation.
AB  - Inflammation initiates clotting, decreases the activity of natural anticoagulant
      mechanisms and impairs the fibrinolytic system. Inflammatory cytokines are the
      major mediators involved in coagulation activation. The natural anticoagulants
      function to dampen elevation of cytokine levels. Furthermore, components of the
      natural anticoagulant cascades, like thrombomodulin, minimise endothelial cell
      dysfunction by rendering the cells less responsive to inflammatory mediators,
      facilitate the neutralisation of some inflammatory mediators and decrease loss of
      endothelial barrier function. Hence, downregulation of anticoagulant pathways not
      only promotes thrombosis but also amplifies the inflammatory process. When the
      inflammation-coagulation interactions overwhelm the natural defence systems,
      catastrophic events occur, such as manifested in severe sepsis or inflammatory
      bowel disease.

PMID- 16281933
TI  - Advances in the understanding of the congenital dyserythropoietic anaemias.
AB  - The congenital dyserythropoietic anaemias (CDAs) are a heterogeneous group of
      diseases in which the anaemia is predominantly caused by dyserythropoiesis and
      marked ineffective erythropoiesis; three major (types I, II and III) and several
      minor subgroups have been identified. Additional information on the natural
      history of these conditions, the beneficial role of splenectomy in CDA type II
      and efficacy of interferon-alpha in type I have recently been reported. A disease
      gene has been localised to a chromosomal segment in the three major types and in
      CDA type I, a disease gene has been identified (CDANI). Mutations have been
      detected in both familial and sporadic cases but the predicted protein structure
      gives few clues as to its function. In both type I and II, there are cases
      unlinked to the identified localisations, suggesting genetic heterogeneity.

PMID- 16281934
TI  - The gene expression signature of relapse in paediatric acute lymphoblastic
      leukaemia: implications for mechanisms of therapy failure.
AB  - Despite significant improvements in the treatment of childhood acute
      lymphoblastic leukaemia (ALL), the prognosis for relapsing patients remains poor.
      The aim of this study was to generate a transcriptional profile of relapsed ALL
      to increase our understanding of the mechanisms involved in therapy failure. RNA
      was extracted from 11 pairs of cryopreserved pre-B ALL bone marrow specimens
      taken from the same patients at diagnosis and relapse, and analysed using HG
      U133A microarrays. Relapse specimens overexpressed genes that are involved with
      cell growth and proliferation, in keeping with their aggressive phenotype. When
      tested in 72 independent specimens of pre-B ALL and T-ALL, the identified genes
      could successfully differentiate between diagnosis and relapse in either lineage,
      indicating the existence of relapse mechanisms common to both. These genes have
      functions relevant for oncogenesis, drug resistance and metastasis, but are not
      related to classical multidrug-resistance pathways. Increased expression of the
      top-ranked gene (BSG) at diagnosis was significantly associated with adverse
      outcome. Several chromosomal loci, including 19p13, were identified as potential
      hotspots for aberrant gene expression in relapsed ALL. Our results provide
      evidence for a link between drug resistance and the microenvironment that has
      previously only been considered in the context of solid tumour biology.

PMID- 16281935
TI  - Molecular typing of adult acute myeloid leukaemia: significance of
      translocations, tandem duplications, methylation, and selective gene expression
      profiling.
AB  - Although a number of molecular aberrations have been described in acute myeloid
      leukaemia (AML), no study has yet determined their relative prognostic
      importance. We have analysed blast cells from 250 adult patients treated at the
      same institution during a 15-year period. Balanced translocations were detected
      by multiplex polymerase chain reaction in 13% of the cases. Internal tandem
      duplication (ITD) of the FLT3 gene and partial tandem duplication of the MLL gene
      were found in 24% and 4%, respectively. Promoter hypermethylation of the P15,
      CDH1, ER and MDR1 genes was observed in 71%, 64%, 40% and 4%, respectively.
      Compared with normal bone marrow, the chemotherapy resistance protein MRP1 and
      apoptosis related genes BAX and CASPASE3 were found to be overexpressed in AML
      blasts. Univariate analysis revealed that the most important determinants of
      prognosis were presence of balanced translocations, age, white blood cell count
      and extramedullary disease, in order of statistical significance. In a
      multivariate analysis, balanced translocations retained their prognostic
      significance and FLT3 ITD as well as high gene expression of MDR1 were negative
      prognostic factors. From these data, which are the first to compare these
      molecular aberrations directly, we conclude that, when a battery of molecular
      changes is evaluated for upfront significance in AML, recurrent translocations
      are of prime importance for treatment outcome.

PMID- 16281936
TI  - Primary diffuse large B-cell non-Hodgkin lymphoma of the paranasal sinuses: a
      report of 14 cases.
AB  - Sinonasal lymphoma (SL) is a rare form of extranodal lymphoma. Of 33 SL cases, 14
      consecutive diffuse large B-cell lymphomas were treated with CHOP (adriamycin,
      cyclophosphamide, vincristine and prednisone) or CHOP-like chemotherapy regimen.
      Ten achieved complete remission (CR) and three achieved a partial remission. With
      a median follow-up period of 80 months, seven patients relapsed or progressed
      [one case including central nervous system (CNS) progression]. Four of the
      relapses involved the CNS. Eight patients were alive, including seven in CR and
      six patients had died of their lymphoma. This observation strongly suggests that
      CNS prophylaxis should be used in SL.

PMID- 16281937
TI  - Evaluation of cytomegalovirus-specific T-cell reconstitution in patients after
      various allogeneic haematopoietic stem cell transplantation using interferon
      gamma-enzyme-linked immunospot and human leucocyte antigen tetramer assays with
      an immunodominant T-cell epitope.
AB  - Cytomegalovirus (CMV) infection is a major complication for patients who received
      allogeneic haematopoietic stem cell transplantation (HSCT). Accurate monitoring
      of CMV-specific T-cell reconstitution is required for appropriate decision on
      treatment, such as anti-viral drugs, which have adverse effects. Although human
      leucocyte antigen (HLA) tetramer and interferon-gamma-enzyme-linked immunospot
      (IFN-gamma-ELISPOT) assays have been used to measure CMV-specific T cells,
      detailed comparison of these assays and kinetics of anti-CMV T-cell
      reconstitution between reduced-intensity transplantation (RIST) and conventional
      HSCT has not yet been performed. In this study, we performed prospective
      comparative monitoring of CMV-specific T cells using HLA tetramer and IFN-gamma
      ELISPOT assays with a single immunodominant CMV(495) peptide in 28 HLA-A*0201 and
      9 HLA-A*0206 patients after various allogeneic HSCTs. The IFN-gamma-ELISPOT assay
      was more sensitive for evaluation of functional T cells than the HLA tetramer
      assay, and CMV-specific T cells were reconstituted earlier in patients who
      received RIST without anti-thymocyte globulin (ATG) than those receiving RIST
      with ATG or conventional HSCT. The threshold level for protection from CMV
      reactivation was estimated as over 1 x 10(6) cells/l peripheral blood with the
      IFN-gamma-ELISPOT assay. These results demonstrate that the IFN-gamma-ELISPOT
      assay with CMV(495) provides more accurate evaluation on CMV immunity in HLA
      A*0201 and -A*0206 patients, and may be useful for determining timing of various
      treatments.

PMID- 16281938
TI  - Infections with human herpesvirus 6 variant B delay platelet engraftment after
      allogeneic haematopoietic stem cell transplantation.
AB  - The clinical significance of human herpesvirus (HHV-6) infections after
      allogeneic stem cell transplantation (SCT) remains controversial. We analysed
      cryoconserved plasma samples from 82 patients after allogeneic SCT by
      quantitative polymerase chain reaction for HHV-6 variants A and B. Platelet
      engraftment was delayed in patients with HHV-6B infections but not with HHV-6A
      infections detected before day +28. In multivariate analysis early HHV-6B
      infections and the type of conditioning were associated with platelet
      engraftment. In conclusion, the two variants of HHV-6 should be studied
      separately; early infections with HHV-6B may contribute to delayed platelet
      engraftment after allogeneic SCT.

PMID- 16281939
TI  - Homozygosity for human leucocyte antigen-C ligands of KIR2DL1 is associated with
      increased risk of relapse after human leucocyte antigen-C-matched unrelated donor
      haematopoietic stem cell transplantation.
AB  - Human leucocyte antigen (HLA)-C molecules regulate the function of natural killer
      cells and may be subdivided into two groups, C(1) and C(2), based on their
      specificity for inhibitory killer immunoglobulin-like receptors. We analysed the
      impact of the HLA-C genotype on outcome of HLA-C-matched unrelated donor
      haematopoietic stem cell transplantation (URD-HSCT) recipients. HLA-C(2)
      homozygous patients (n = 18) had lower probability of overall survival (P = 0.01)
      and disease-free survival (P = 0.02), resulting from increased relapse rate (P =
      0.02) when compared with both HLA-C(1) homozygous (n = 43) and HLA-C(1),C(2)
      heterozygous (n = 50) subgroups. Patients lacking HLA-C(1) should, therefore, be
      considered at increased risk of relapse following HLA-C-matched URD-HSCT.

PMID- 16281940
TI  - Circulating microparticles are elevated in haemophiliacs and non-haemophilic
      individuals aged <18 years.
AB  - Platelet and cell stimulation lead to plasma membrane remodelling, resulting in
      phosphatidylserine (PS) externalisation in the outer leaflet of the membrane,
      associated with the shedding of PS-rich microparticles (MPs), and contributes to
      thrombin generation by promoting the assembly of coagulation enzyme complexes. A
      previous study assessed MP levels in haemophiliacs after haemostatic treatment.
      To further investigate in vivo membrane remodelling, MP levels and
      characteristics were studied in 79 haemophiliacs and in 62 non-haemophiliacs.
      Both groups showed heterogeneity in MP levels, with higher values in individuals
      <18 years. This finding should be considered when studying MP levels in
      individuals <18 years.

PMID- 16281941
TI  - The expression of minichromosome maintenance protein-2 in normal and abnormal
      megakaryocytes and comparison with the proliferative marker Ki-67.
AB  - The minichromosome maintenance (Mcm) and Cdc6 proteins are important regulators
      of eucaryotic DNA replication. In most normal tissues, a similar proportion of
      cells express Mcm-2 and Ki-67. The present study showed that in both normal and
      abnormal states, the proportion of megakaryocytes expressing Mcm-2 is roughly
      seven times as many as those that express Ki-67. This is likely to be related to
      the process of endomitosis and endoreduplication. We also demonstrated that a
      significantly lower proportion of megakaryocytes in myelodysplastic syndrome
      express Mcm-2. These findings provide new insights into megakaryocyte biology.

PMID- 16281942
TI  - Haploinsufficiency of Runx1/AML1 promotes myeloid features and leukaemogenesis in
      BXH2 mice.
AB  - Haploinsufficiency of RUNX1/AML1 is associated with familial platelet disorder
      with a predisposition to acute myeloid leukaemia (FPD/AML), but the causal
      relationship remains to be addressed experimentally. Mice heterozygous for the
      Runx1 null mutation, Runx1+/-, are considered to be genetically comparable with
      human FPD/AML patients but do not develop spontaneous leukaemia. To induce
      additional genetic alterations, retroviral insertional mutagenesis was employed
      with the use of BXH2 mice, which develop myeloid leukaemia because of the random
      integration of retrovirus present in the mouse. Heterozygous disruption of Runx1
      in BXH2 mice resulted in a shortening of the latency period of leukaemia. In
      addition, BXH2-Runx1+/- mice exhibited more marked myeloid features than control
      mice. Moreover, the c-Kit gene, mutated in human RUNX leukaemias, was recurrently
      activated in BXH2-Runx1+/- mice, and a colony-forming assay revealed synergism
      between the Runx1+/- status and c-KIT overexpression. In conclusion, the BXH2
      Runx1+/- system is a promising mouse model to investigate the mechanism of
      leukaemogenesis in FPD/AML.

PMID- 16281943
TI  - Circulating CD10-/CD16low neutrophils provide a quantitative index of active bone
      marrow neutrophil release.
AB  - Circulating neutrophil phenotype and function are altered during neutrophilia
      associated with acute inflammatory states, however, the contribution of bone
      marrow neutrophil release to these changes has been difficult to quantify in
      humans. Accelerated release of neutrophils, with potentially distinct attributes,
      from the bone marrow and their dilution within the circulating pool may produce
      these apparent changes. Unfortunately selective analysis of these newly emergent
      neutrophils is difficult given their morphologic similarity to those already in
      the circulation and the coincident effect of soluble inflammatory mediators on
      circulating neutrophil phenotype and function. Using whole blood flow cytometry
      and cardiac surgery as an inflammatory stimulus, we demonstrate the emergence of
      a unique subpopulation of circulating neutrophils characterised as CD10(
      )/CD16(low), indicative of active bone marrow neutrophil release peri
      operatively. CD10(-)/CD16(low) neutrophils emerge at the same operative stages as
      band forms and a left shift, yet represent over 40% of circulating neutrophils
      postoperatively, and generate a greater stimulus-induced [Ca(2+)](i) flux than
      their CD10(+) counterparts. We conclude that CD10(-)/CD16(low) neutrophils
      represent a significant proportion of the circulating pool after cardiac surgery
      and that bone marrow release, a major contributor to neutrophilia, influences the
      phenotype and functional activity of circulating neutrophils following this acute
      inflammatory stimulus.

PMID- 16281944
TI  - The synthetic furanonaphthoquinone induces growth arrest, apoptosis and
      differentiation in a variety of leukaemias and multiple myeloma cells.
AB  - 2-methyl-naphtho[2,3-b]furan-4,9-dione (FNQ3), a synthetic analogue of the
      quinone kigelinone, has demonstrated a real potential for use in the treatment of
      a variety of solid tumours. Unlike other quinones, such as mitomycin-C and
      adriamycin, the cytotoxicity of FNQ3 is often 10- to 14-fold more potent towards
      the tumour cells than their normal counterparts. We report, for the first time,
      that the drug had activity against a broad spectrum of leukaemias and multiple
      myeloma cells. It decreased the growth of acute myeloid leukaemia (AML) and
      multiple myeloma cell lines in a dose-dependent fashion (50% inhibitory
      concentration approximately 1.25 microg/ml against most of the leukaemia cell
      lines). This dose apparently initiated mitochondrial collapse as measured by
      depolarisation of the mitochondrial membrane. FNQ3 potentiated the
      differentiation of HL-60 myeloid cells in the presence of either 1alpha,
      25(OH)(2) dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] or all-trans-retinoic acid
      (ATRA). FNQ3 inhibited the proliferation of primary AML cells while inducing
      apoptosis. Eleven of 14 (79%) AML marrow samples had a prominent decrease in
      their clonogenic growth when cultured in the presence of the drug. In summary,
      this drug has growth inhibitory, apoptotic and differentiative effects against
      myeloid leukaemias and multiple myeloma cells. FNQ3 may represent a new
      therapeutic approach to these malignancies.

PMID- 16281945
TI  - Windy weather and low humidity are associated with an increased number of
      hospital admissions for acute pain and sickle cell disease in an urban
      environment with a maritime temperate climate.
AB  - Sickle cell disease (SCD) is characterised by intermittent episodes of acute
      severe pain, related to vaso-occlusion. Environmental factors are thought to play
      an important role, and studies in tropical countries have suggested that cold and
      rainy seasons are associated with increased episodes of acute pain. We have
      studied retrospectively the number of admissions with acute pain and SCD to
      King's College Hospital, London, together with daily meteorological records
      collected locally. Data from 1400 d and 1047 separate admissions were analysed.
      Increased admissions were significantly associated with increased wind speed and
      low humidity, but showed no relationship to temperature, rainfall or barometric
      pressure. The strongest effect was for (maximum wind speed)/humidity, with 464
      admissions on days in the lowest two quartiles of this parameter and 582 in the
      highest quartiles. The effect of high wind and low humidity is likely to be
      related to skin cooling.

PMID- 16281946
TI  - Erythropoietin levels in the different clinical forms of hereditary
      spherocytosis.
AB  - Erythropoietin (EPO), the main growth factor responsible for the regulation of
      red blood cell production, may be overproduced when blood loss or haemolysis
      occurs. Patients with mild hereditary spherocytosis (HS) are able to maintain
      normal haemoglobin concentration, whereas typical and severe HS patients develop
      an anaemic state. Splenectomy usually reverses anaemia. We aimed to clarify the
      role of EPO in the response to enhanced spherocyte destruction, and to look for a
      linkage with the broad clinical spectra of HS. EPO levels, reticulocyte count and
      production index (RPI), other parameters used to classify HS and the protein
      deficiencies underlying HS were evaluated in previously diagnosed
      unsplenectomised (n = 24) and splenectomised (n = 10) patients presenting mild,
      typical or severe HS. A significant increase in EPO was observed in all
      unsplenectomised HS patients. In the mild form, a significant correlation of EPO
      with reticulocyte count and RPI was observed; however, this correlation
      disappeared in typical HS patients. Splenectomised HS patients presented a
      correction in EPO levels in all forms of HS, although the reticulocyte count and
      RPI sustained slightly higher values. Our data show HS as a disease linked to an
      overproduction of EPO, according to the severity of the disease; however, a
      disturbance in erythropoiesis seems to occur in typical HS. Moreover, splenectomy
      leads to a correction in the EPO levels.

PMID- 16281947
TI  - Modelling the human rhesus proteins: implications for structure and function.
AB  - The mammalian rhesus (Rh) proteins that carry the Rh blood group antigens of red
      blood cells are related to the ammonium channel (Amt) proteins found in both pro-
      and eukaryotes. However, despite their clinical importance the structure of the
      Rh antigens is presently unknown. We have constructed homology models of the
      human Rh proteins, RhD and RhAG using the structure of the Escherichia coli
      ammonia channel AmtB as a template, together with secondary structure predictions
      and the extensive available biochemical data for the Rh proteins. These models
      suggest that RhAG and the homologous non-erythrocyte Rhesus glycoproteins, RhBG
      and RhCG, have a very similar channel architecture to AmtB. By comparison, RhD
      and RhCE have a different arrangement of residues, indicating that if they
      function as ammonia channels at all, they must do so by a different mechanism.
      The E. coli AmtB protein is a homotrimer and our models provoke a reassessment of
      the widely accepted tetrameric model of the organisation of the erythrocyte Rh
      complex. A critical analysis of previously published data, together with
      sequencing yield data, lead us to suggest that the erythrocyte Rh complex could
      indeed also be trimeric.

PMID- 16281948
TI  - P53 codon 72 polymorphism is associated with disease progression in adult T-cell
      leukaemia/lymphoma.

PMID- 16281949
TI  - Annexin A2 may not play a role as a plasminogen receptor.

PMID- 16281952
TI  - Erythropoiesis and red cell function in vertebrate embryos.
AB  - All vertebrate embryos produce a specific erythroid cell population--primitive
      erythrocytes--early in development. These cells are characterized by expression
      of the specific embryonic haemoglobins. Many aspects of primitive erythropoiesis
      and the physiological function of primitive red cells are still enigmatic.
      Nevertheless, recent years have seen intensive efforts to characterize in greater
      detail the molecular events underlying the initiation of erythropoiesis in
      vertebrate embryos. Several key genes have been identified that are necessary for
      primitive and the subsequent definitive erythropoiesis, which differs in several
      aspect from primitive erythropoiesis. This review gives in its first part a short
      overview dealing with comparative aspects of primitive and early definitive
      erythropoiesis in higher and lower vertebrates and in the second part we discuss
      the physiological function of primitive red cells based mainly on results from
      mammalian and avian embryos.

PMID- 16281953
TI  - Regulation of erythropoietin production.
AB  - The glycoprotein hormone erythropoietin (EPO) is an essential growth and survival
      factor for erythroid progenitor cells, and the rate of red blood cell production
      is normally determined by the serum EPO concentration. EPO production is
      inversely related to oxygen availability, so that an effective feedback loop is
      established, which controls erythropoiesis. Since recombinant EPO became
      available as an effective therapeutic agent, significant progress has also been
      made in understanding the basis of this feedback control. The main determinant of
      EPO synthesis is the transcriptional activity of its gene in liver and kidneys,
      which is related to local oxygen tensions. This control is achieved by hypoxia
      inducible transcription factors (HIF), consisting of a constitutive beta-subunit
      and one of two alternative oxygen-regulated HIFalpha subunits (HIF-1alpha and HIF
      2alpha). In the presence of oxygen (normoxia) the HIFalpha subunits are
      hydroxylated, which targets them for proteasomal degradation. Under hypoxia,
      because of the lack of molecular oxygen, HIF cannot be hydroxylated and is
      thereby stabilized. Although HIF-1alpha was the first transcription factor
      identified through its ability to bind to an enhancer sequence of the EPO gene,
      more recent evidence suggests that HIF-2alpha is responsible for the regulation
      of EPO. Although EPO is a prime example for an oxygen- regulated gene, the role
      of the HIF system goes far beyond the regulation of EPO, because it operates
      widely in almost all cells and controls a broad transcriptional response to
      hypoxia, including genes involved in cell metabolism, angiogenesis and vascular
      tone. Further evidence suggests that apart from its effect as an erythropoietic
      hormone EPO acts as a paracrine, tissue-protective protein in the brain and
      possibly also in other organs.

PMID- 16281954
TI  - Anaemia and the heart.
AB  - Anaemia is common in patients with congestive heart failure (CHF). Its prevalence
      increases with disease severity as a consequence of renal insufficiency, cytokine
      production, blood loss, iron deficiency, malnutrition and/or plasma volume
      overload. Anaemia can contribute to worsening of CHF. There is a nonlinear
      relationship (U-shaped curve) between haemoglobin and survival. Prevalence of
      anaemia among elderly people with acute myocardial infarction is high and is
      associated with more frequent in-hospital events, including death. Anaemia is
      also associated with higher in-hospital mortality rate after coronary bypass
      surgery and with all-cause and cardiac mortality after percutaneous coronary
      interventions. Patients with anaemia and cardiovascular disease have a higher
      mortality rate after cardiac/noncardiac surgery as compared to those with anaemia
      but without cardiovascular disease or those with cardiovascular disease but
      without anaemia. However, not all authors confirmed these findings. Therefore,
      multicentre trials to clarify this issue are urgently needed. Pleiotropic effects
      of recombinant human erythropoietin include reduction of myocardial and cerebral
      infarct size without an increase in haematocrit, neovascularization as well as
      mobilization of endothelial progenitor cells.

PMID- 16281955
TI  - Anaemia in cancer patients: pathophysiology, incidence and treatment.
AB  - This review focuses on the pathophysiology, incidence and treatment of anaemia in
      cancer patients. Causative factors such as different chemotherapy regimens and
      patient risk factors for the development of anaemia are discussed in order to
      identify the patient group that is most likely to receive red blood cell
      transfusions and would thus have the largest benefit from treatment with
      erythropoietic proteins. The data available with recombinant human erythropoietin
      alfa, recombinant human erythropoietin beta and darbepoetin alfa are described in
      more detail and the significant benefit of treating cancer anaemia by these
      molecules is outlined. Finally, differences in treatment approaches between these
      erythropoietic proteins are discussed in order to guide treatment decisions
      specific for the individual patients' situation.

PMID- 16281956
TI  - Hyporesponsiveness to erythropoietic therapy due to chronic inflammation.
AB  - The anaemia associated with chronic renal failure is multi-factorial. Although a
      relative erythropoietin deficiency is a major factor, it has also been recognized
      in recent times that uraemia is a chronic inflammatory state, and thus patients
      with renal failure also develop anaemia due to mechanisms associated with chronic
      inflammation. Thus, patients with chronic renal failure have activation of
      various immune cells, both monocytes and T-cells. These mononuclear cells have
      also been shown to release pro-inflammatory cytokines such as IL-1, IL-6, TNF
      alfa and interferon gamma. These cytokines, particularly TNF-alfa and interferon
      gamma, are known to cause significant suppression of erythropoiesis. The exact
      molecular mechanism for this effect is not yet clear, but interferon gamma is an
      important stimulator of apoptosis in various cell types, including erythroid
      progenitor cells. This effect may be potentiated by other cytokines such as TNF
      alfa, and this might then antagonise the anti-apoptotic action of erythropoietin
      on erythroid progenitors cells, thus reducing responsiveness to exogenous
      erythropoietic therapy. Chronic renal failure is also associated with increased
      hepcidin production which may also exacerbate the anaemia by inducing a
      functional iron deficiency in such patients.

PMID- 16281957
TI  - Benefits and risks of iron therapy for chronic anaemias.
AB  - Iron is used widely for the treatment of anaemias with iron-restricted
      erythropoiesis. This intervention can be both beneficial and detrimental
      depending on the type of the underlying process. While in iron deficiency anaemia
      (IDA), the most frequent anaemia in the world, iron is the therapy of choice,
      this intervention can be harmful in the anaemia of chronic disease or anaemia
      associated with renal failure, the most common anaemias in hospitalized adult
      patients in Western countries. Iron is able to negatively affect cell-mediated
      immune effector mechanisms directed against invading microorganisms and tumour
      cells while at the same time, as an essential nutrient, it can stimulate the
      proliferation of these unwanted cells. In addition, iron catalyses the formation
      of toxic radicals leading to tissue damage or the promotion of cardiovascular
      events. Thus, it is essential to correctly diagnose the precise cause of anaemia
      and to consider the benefits and hazards of targeted iron therapy.

PMID- 16281958
TI  - Intravenous iron therapy: well-tolerated, yet not harmless.
AB  - In the majority of patients with chronic renal failure, it is essential to
      substitute erythropoietic agents and iron to maintain a haemoglobin level above
      11 g dL-1. Intravenous iron is more effective than oral iron. Substitution of
      intravenous iron is mainly performed using iron(III)-hydroxide-sucrose complex
      (iron sucrose) and iron(III)-sodium-gluconate in sucrose (iron gluconate), and
      is, in general, well-tolerated. Nonetheless, intravenous iron therapy has effects
      on endothelial cells, polymorphonuclear leucocytes and cytokines which are most
      likely related to non-transferrin bound labile iron. These effects suggest a role
      of iron in infection or atherosclerosis. Yet, not all available data support the
      association of iron with infection and atherosclerosis. A recent trial showed
      that iron sucrose is safe when given as treatment for iron deficiency or for
      maintenance of iron stores. Nevertheless, iron therapy should be handled with
      caution but its use should not be feared whenever indicated.

PMID- 16281959
TI  - Sex, haemoglobin and kidney disease: new perspectives.
AB  - Anaemia is recognized as a common complication of chronic kidney disease with
      significant associated morbidity and mortality. Published data document the
      negative impact of anaemia on cardiovascular disease outcomes, progression of
      chronic kidney disease (CKD), hospitalizations, rehabilitation and quality of
      life, among others. Gender differences have been identified in many of these
      areas as well as, and importantly, in cardiovascular and chronic kidney disease
      outcomes. Female gender is associated with lower risk of cardiovascular morbidity
      and mortality as well as slower progression of chronic kidney disease.
      Interestingly, there are some well-described physiological adaptations to anaemia
      in women, which include shifting of the haemoglobin oxygen dissociation curve to
      reduce oxygen affinity secondary to higher levels of 2,3-diphosphoglycerate.
      However, the complex physiology underlying the impact of anaemia or gender on
      patients with chronic kidney disease is not well-characterized to date.
      Furthermore, there has been little examination of the potential interaction
      between anaemia and gender on cardiac or kidney outcomes. In this paper, we
      review the documented impact of anaemia and gender on outcomes, and explore the
      interaction of anaemia and gender in patients with CKD. We also present data that
      describe the potential importance of considering gender when targeting specific
      levels of haemoglobin. The value of a new perspective on haemoglobin and gender
      in kidney disease is important from both a physiological and an economical
      perspective.

PMID- 16281960
TI  - The epidemiology and control of anaemia among pre-ESRD patients with chronic
      kidney disease.
AB  - Anaemia is a common condition among pre-end-stage renal disease (pre-ESRD)
      patients with chronic kidney disease (CKD). Indeed, data from clinical studies
      indicate that anaemia may be present in as many as two-thirds of such patients.
      Use of recombinant human erythropoietin (EPO) provides an effective means of
      correcting anaemia in CKD patients and helps to reduce the risk of renal disease
      progression and related problems. Unfortunately, EPO therapy is underutilized in
      these persons. Consequently, anaemia remains a major problem in the pre-ESRD CKD
      population. Evidence suggests that anaemia in the presence of CKD can lead to an
      increased risk of a number of adverse outcomes, including mortality, progression
      of kidney disease, coronary heart disease, stroke, hospitalization, and decreases
      in quality of life. Anaemia's association with these adverse outcomes suggests
      that effective treatment of anaemia in pre-ESRD CKD patients is of great
      importance and that substantial efforts should be made to ensure that these
      patients receive appropriate therapy to correct anaemia.

PMID- 16281962
TI  - Hormonal adjuvants for the treatment of renal anaemia.
AB  - Hormonal adjuvants, besides being erythropoietic agents, broaden the spectrum of
      therapeutic options for the treatment of the anaemia of chronic kidney disease
      (CKD). Lowering elevated parathyroid hormone levels by oral calcium
      supplementation and phosphate restriction, by varying dialysate calcium
      concentrations, by administration of vitamin D3 derivatives and, in the near
      future, by treatment with calcimimetics may prove efficient in some patients to
      fight extensive requirements of erythropoietic agents. Clinical evidence for a
      principal role of secondary hyperparathyroidism in resistance to erythropoietin,
      however, is lacking. Active vitamin D3 derivatives, in addition to their
      beneficial effects on secondary hyperparathyroidism, appear to exert a direct,
      stimulatory action on erythroid precursor cells and possibly also an inhibitory
      action on collagen synthesis by bone marrow stromal cells. Growth hormone (GH)
      induces insulin-like growth factor (IGF)-1, which in turn counteracts apoptosis
      similarly to erythropoietin, and fosters proliferation of burst- and colony
      forming units-erythroid (BFU-E, CFU-E). If erythropoietic agents improve survival
      of CKD patients, a similar benefit should apply for strategies that increase
      synthesis and bioavailabilty of IGF-1. The latter appears to be reduced in CKD
      patients, and zinc supplementation potentially enhances it via an increase in
      free IGF-1. Finally, androgens also exert anti-anaemic effects. Nandrolone
      decanoate constitutes the only androgen currently applicable for selected male
      dialysis patients over the age of 50 years. It should not be given to women,
      however, because of serious side effects. Collectively, hormonal interventions
      offer the potential to reduce requirements of erythropoietic agents, and some may
      also improve physical performance.

PMID- 16281961
TI  - Diabetic nephropathy and anaemia.
AB  - Anaemia is a frequent complication of diabetic nephropathy. It has only recently
      been recognised that in diabetic patients anaemia is seen not only in preterminal
      renal failure, but also frequently in patients with only minor derangement of
      renal function. At any level of glomerular filtration rate (GFR) anaemia is more
      frequent and severe in diabetic compared to nondiabetic patients. A major cause
      of anaemia is an inappropriate response of erythropoietin to anaemia. Additional
      factors are iron deficiency and iatrogenic factors, e.g. ACE inhibitor treatment.
      When serum creatinine is still normal, the erythropoietin concentration is
      predictive of more rapid loss of glomerular function. When serum creatinine is
      elevated, the haemoglobin values are predictive of the rate of progression. It is
      currently under investigation whether reversal of anaemia attenuates the rate of
      progression. Because most of the late complications of diabetes (retinopathy,
      neuropathy, heart disease, peripheral arterial disease) involve ischaemic tissue
      damage, it would be intuitively plausible that treatment with human recombinant
      erythropoietin should be beneficial, but definite evidence for this hypothesis is
      currently not available.

PMID- 16281963
TI  - Arterial structural and functional alterations in uraemia.
AB  - Epidemiological and clinical studies have shown that cardiovascular disease in
      patients with end-stage renal disease (ESRD) is frequently related to damage of
      large conduit arteries. Arterial disease is responsible for the high incidence of
      ischaemic heart disease, peripheral artery diseases, left ventricular hypertrophy
      and congestive heart failure. The vascular complications in ESRD are ascribed to
      two different but associated mechanisms, namely atherosclerosis and
      arteriosclerosis. Whereas the former principally affects the conduit function
      with ischaemic lesions being the most characteristic consequence, the latter
      primarily disturbs the dampening function of large arteries. Arteriosclerosis in
      ESRD patients is characterized by diffuse dilation and wall hypertrophy of large
      conduit arteries and stiffening of arterial walls. These changes represent a
      clinical form of an accelerated ageing process. The main clinical characteristics
      due to arterial stiffening are isolated increase in systolic blood pressure with
      normal or lower diastolic pressure resulting in an increased pulse pressure. The
      consequences of these alterations are: (i) an increased left ventricular
      afterload with development of left ventricular hypertrophy and increased
      myocardial oxygen demand; and (ii) altered coronary perfusion and subendocardial
      blood flow distribution. Epidemiological studies have identified arterial
      remodelling and stiffening as independent predictors of overall and cardiac
      mortality in ESRD patients.

PMID- 16281964
TI  - Anaemia after renal transplantation.
AB  - Anaemia is a frequent complication among long-term renal transplant recipients. A
      prevalence of approximately 40% has been reported in several studies. If renal
      function declines to stage 5 kidney disease, the prevalence of anaemia in kidney
      transplants is even higher. A positive correlation between haemoglobin
      concentration and creatinine clearance has been reported, which is a function of
      endogenous erythropoietin production by the functioning graft. Inflammation
      related to a retained kidney graft may cause hypo-responsiveness to
      erythropoietic agents once kidney transplant recipients return to dialysis.
      Furthermore, the use of azathioprine, mycophenolate mofetil and sirolimus may be
      associated with post-transplant anaemia. Along with erythropoietin deficiency,
      depletion of iron stores is one of the major reasons for anaemia in the kidney
      transplant population. The proportion of hypochromic red blood cells appears to
      be a useful parameter to measure iron supply and utilization as well as to
      estimate mortality risks in kidney transplant recipients. While anaemia is an
      important cardiovascular risk-factor after transplantation, our data suggest that
      anaemia is not associated with mortality and graft loss. Nevertheless, inadequate
      attention is paid so far to the management of anaemia after renal
      transplantation. A promising future aspect for risk reduction of cardiovascular
      disease includes the effect of erythropoietic agents on endothelial progenitor
      cells.

PMID- 16281965
TI  - Erythropoietin-induced, antibody-mediated pure red cell aplasia.
AB  - Pure red cell aplasia (PRCA) is a rare haematological condition that is
      characterized by severe aregenerative anaemia due to an almost complete cessation
      of red blood cell production. While antibody-mediated PRCA was extremely rare
      before 1998, the incidence of this disorder increased sharply after 1998 in
      patients receiving subcutaneous epoetin alfa produced by Ortho-Biotech and
      marketed outside the USA. The diagnosis of antibody-mediated PRCA relies mostly
      on the results of bone marrow biopsy or aspirate, which shows an absence of
      erythroid precursors and/or red cell maturation arrest while counts of white cell
      and platelet precursors are normal, and on the identification of circulating anti
      erythropoietin antibodies. Retrospective analysis of PRCA cases has shown that
      immunosuppressive therapy can induce a disappearance of anti-erythropoietin
      antibodies in most patients. Eur J Clin Invest 2005; 35 (Suppl. 3): 95-99.

PMID- 16281966
TI  - The National Anaemia Action Council, Inc.: the primary North American resource
      for anaemia education and research.
AB  - The mission of the National Anaemia Action Council, Inc. (NAAC) is to raise the
      awareness of health care professionals and the public regarding the prevalence,
      symptoms, consequences and under-treatment of anaemia. This editorial illustrates
      the goals and objectives of NAAC, and depicts past, present and future
      educational and research projects and findings. NAAC resources in anaemia-related
      education and research are described in detail.

PMID- 16281967
TI  - "Saying no is no easy matter" a qualitative study of competing concerns in
      rationing decisions in general practice.
AB  - BACKGROUND: The general practitioner in Norway is expected to ensure equity and
      effectiveness through fair rationing. At the same time, due to recent reforms of
      the Norwegian health care sector, both the role of economic incentives and
      patient autonomy have been strengthened. Studies indicate that modern general
      practitioners, both in Norway and in other countries are uncomfortable with the
      gatekeeper role, but there is little knowledge about how general practitioners
      experience rationing in practice. METHODS: Through focus group interviews with
      Norwegian general practitioners, we explore physicians' attitudes toward factors
      of influence on medical decision making and how rationing dilemmas are
      experienced in everyday practice. RESULTS: Four major concerns appeared in the
      group discussions: The obligation to ration health care, professional autonomy,
      patient autonomy, and competition. A central finding was that the physicians find
      rationing difficult because saying no in face to face relations often is felt
      uncomfortable and in conflict with other important objectives for the general
      practitioner. CONCLUSION: It is important to understand the association between
      using economic incentives in the management of health care, increasing patient
      autonomy, and the willingness among physicians to contribute to efficient, fair
      and legitimate resource allocation.

PMID- 16281968
TI  - Specific distribution of overexpressed aurora B kinase during interphase of
      normal epithelial cells.
AB  - BACKGROUND: It is known that aurora B, a chromosomal passenger protein
      responsible for the proper progression of mitosis and cytokinesis, is
      overexpressed throughout the cell cycle in cancer cells. Overexpression of aurora
      B produced multinuclearity and induced aggressive metastasis, suggesting that
      overexpressed aurora B has multiple functions in cancer development. However, the
      detailed dynamics and functions of overexpressed aurora B are poorly understood.
      RESULTS: We overexpressed GFP fused aurora B kinase in normal rat kidney
      epithelial cells. Using spinning disk confocal microscopy, we found that
      overexpressed aurora B-GFP was predominantly localized in the nucleus and along
      the cortex as a dot-like or short filamentous structure during interphase. Time
      lapse imaging revealed that a cytoplasmic fraction of overexpressed aurora B-GFP
      was incorporated into the nucleus after cell division. Immunofluorescence showed
      that the nuclear fraction of overexpressed aurora B did not induce ectopic
      phosphorylation of histone H3 after cell division. The cytoplasmic fraction of
      overexpressed aurora B-GFP was mainly associated with cortical actin filaments
      but not stress fibers. Myosin II regulatory light chain, one of the possible
      targets for aurora B, did not colocalize with cortical aurora B-GFP, suggesting
      that overexpressed aurora B did not promote phosphorylation of myosin II
      regulatory light chain in interphase cells. CONCLUSION: We conclude that
      overexpressed aurora B has a specific localization pattern in interphase cells.
      Based on our findings, we propose that overexpressed aurora B targets the nuclear
      and cortical proteins during interphase, which may contribute to cancer
      development and tumor metastasis.

PMID- 16281969
TI  - Lithuanian health care in transitional state: ethical problems.
AB  - BACKGROUND: Throughout the economic and political reforms in post-communist
      countries, significant changes have also occurred in public morality. One of the
      tasks of the Lithuanian health policy is to create mechanisms for strengthening
      the significance of ethical considerations in the decision-making processes
      concerning health care of individuals and groups of individuals, as well as
      considering the positions of physicians and the health care system itself in a
      general way. Thus, health care ethics could be analyzed at two levels: the micro
      level (the ethics of doctor-patient relationships) and the macro level (the
      ethics of health policy-making, which can be realized by applying the principles
      of equal access, reasonable quality, affordable care and shared
      responsibilities). To date, the first level remains dominant, but the need arises
      for our attention to refocus now from the micro level to the patterns of managing
      and delivering care, managing the health care resources, and conducting business
      practices. DISCUSSION: In attempting to increase the efficiency of health
      services in Lithuania, a common strategy has been in place for the last fifteen
      years. Decentralization and privatization have been implemented as part of its
      policy to achieve greater efficiency. Although decentralization in theory is
      supposed to improve efficiency, in practice the reform of decentralization has
      still to be completely implemented in Lithuania. Debates on health policy in
      Lithuania also include the issue of private versus public health care. Although
      the approach of private health care is changing in a positive way, it is obvious
      that reduced access to health services is the most vulnerable aspect. In the
      Lithuanian Health Program adopted in July 1998, the target of equity was
      stressed, stating that by 2010, differences in health and health care between
      various socio-economic groups should be reduced by 25%. SUMMARY: The
      restructuring of health care system in Lithuania should be based on a balance
      between decentralization and centralization, and between public and private
      health care sectors. Successful transition requires a balanced role of the
      government. Today it is obvious in Lithuania that continuous encouragement to
      make sacrifices was not enough to induce the system to function well, and in an
      ethical manner.

PMID- 16281970
TI  - Immediate endoscopic management of complete iatrogenic anterior urethral
      injuries: a case series with long-term results.
AB  - BACKGROUND: Urethral injury produces partial or complete disruption of the
      urethral integrity. Advances in endourology have made endoscopic management of
      most of these injuries feasible without greatly compromising the final result. We
      report our institutional experience of immediate endoscopic realignment of
      complete iatrogenic anterior urethral injury. METHODS: From May 1997 to May 2003,
      seven patients with complete anterior urethral disruption were managed by
      immediate endoscopy guided splinting of urethra. Retrograde urethroscopy,
      combined with fluoroscopic guidance and in some cases antegrade cystoscopy
      through a suprapubic stab cystostomy was performed. A guide wire was negotiated
      across the disruption. Later, a 16 F Foley catheter was placed for 1-3 weeks.
      Patients were followed up at 1, 3, 6 and 12 months and then yearly to assess the
      long-term outcome of endoscopic management. RESULTS: Immediate endoscopic
      realignment was achieved in all patients. Three patients developed recurrence at
      six months; that was treated by optical urethrotomy. Only one patient developed
      multiple recurrences over an average follow-up of 49.2 months (range 7 to 74
      months). He was offered open end-to-end urethroplasty at twenty months after
      third recurrence. Thus immediate endoscopic realignment avoided any further
      intervention in four patients (57.14%); while after an additional optical
      urethrotomy, urethroplasty could be avoided in six patients (87.2%). CONCLUSION:
      Immediate endoscopic realignment of traumatic urethral disruption is a feasible,
      safe and effective treatment modality for management of patients with iatrogenic
      complete anterior urethral injuries.

PMID- 16281971
TI  - Equine herpesvirus 2 (EHV-2) infection in thoroughbred horses in Argentina.
AB  - BACKGROUND: Equine herpesvirus 2 is a gamma-herpesvirus that infects horses
      worldwide. Although EHV-2 has been implicated in immunosuppression in foals,
      upper respiratory tract disease, conjunctivitis, general malaise and poor
      performance, its precise role as a pathogen remains uncertain. The purpose of the
      present study was to analyse the incidence of EHV-2 in an Argentinean horse
      population and correlate it with age and clinical status of the animals. RESULTS:
      A serological study on 153 thoroughbred racing horses confirmed the presence of
      EHV-2 in the Argentinean equine population. A virus neutralization test showed a
      total of 79.7 % animals were sero-positive for EHV-2. An increase in antibodies
      titre with age as well as infection at earlier ages were observed.EHV-2 was
      isolated from 2 out of 22 nasal swabs from horses showing respiratory symptoms.
      The virus grew slowly and showed characteristic cytopathic effect after several
      blind passages on RK13 cells. The identity of the isolates was confirmed by
      nested PCR and restriction enzyme assay (REA). CONCLUSION: This is the first
      report on the presence of EHV-2 in Argentina and adds new data to the virus
      distribution map. Though EHV-2 was isolated from foals showing respiratory
      symptoms, further studies are needed to unequivocally associate this virus with
      clinical symptoms.

PMID- 16281972
TI  - Development of an improved microneutralization assay for respiratory syncytial
      virus by automated plaque counting using imaging analysis.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the major cause of lower
      respiratory tract infection in infants and young children. Although several
      experimental RSV vaccines are under investigation, immuno therapy is the only
      treatment currently available. In assessing the immunogenicity of various vaccine
      formulations, a plaque reduction neutralization assay for the evaluation of RSV
      neutralizing antibody has been widely used. The method produces reliable results,
      but it is tedious and labor intensive as it relies on manual counting by
      laboratory personnel. To facilitate evaluation of phase II and phase III vaccine
      clinical trials, a more rapid, reliable and efficient neutralization assay is
      needed. RESULTS: An improved microneutralization assay for quantifying RSV
      neutralizing antibodies was developed using an ImmunoSpot Series I Analyzer
      (Cellular Technology Ltd., Cleveland, OH) for automated plaque counting. The
      method is an improvement of the established classical microneutralization assay
      in which immunostained plaques on transparent tissue culture plates are counted
      manually under a dissecting microscope. Image analyzer technology allows for
      fully automated counting of plaques distributed throughout an entire well.
      Adjustments, such as the use of opaque tissue culture plates and the TMB
      substrate, True Blue (KPL, Gaithersburg, MD), were required to adapt the assay
      for optimal detection of plaques by the image analyzer. The suitability and the
      accuracy of the method for counting RSV plaques were determined by comparative
      testing of a reference serum and two control sera by manual and automated
      counting methods. The results showed that the two methods were highly correlated
      (R = 0.9580) and the titers generated by them were within two-fold. CONCLUSION:
      Our results demonstrate that the semi-automated assay is rapid and reliable. It
      provides results within two fold to the classical plaque microneutralization
      assay and is readily applied to the evaluation of neutralizing antibody titers in
      sera obtained from epidemiology or vaccine clinical trials.

PMID- 16281974
TI  - Biochemical characterization of the Arctic char (Salvelinus alpinus) ovarian
      progestin membrane receptor.
AB  - Membrane progestin receptors are involved in oocyte maturation in teleosts.
      However, the maturation-inducing steroid (MIS) does not appear to be conserved
      among species and several progestins may fulfill this function. So far, complete
      biochemical characterization has only been performed on a few species. In the
      present study we have characterized the membrane progestin receptor in Arctic
      char (Salvelinus alpinus) and show that the 17,20beta-dihydroxy-4-pregnen-3-one
      (17,20beta-P) receptor also binds several xenobiotics, thus rendering oocyte
      maturation sensitive to environmental pollutants. We identified a single class of
      high affinity (Kd, 13.8 +/- 1.1 nM), low capacity (Bmax, 1.6 +/- 0.6 pmol/g
      ovary) binding sites by saturation and Scatchard analyses. Receptor binding
      displayed rapid association and dissociation kinetics typical of steroid membrane
      receptors, with t1/2 s of less than 1 minute. The 17,20beta-P binding also
      displayed tissue specificity with high, saturable, and specific 17,20beta-P
      binding detected in ovaries, heart and gills while no specific binding was
      observed in muscle, brain or liver. Changes in 17,20beta-P binding during oocyte
      maturation were consistent with its identity as the oocyte MIS membrane receptor.
      Incubation of fully-grown ovarian follicles with gonadotropin induced oocyte
      maturation, which was accompanied by a five-fold increase in 17,20beta-P receptor
      binding. In addition, competition studies with a variety of steroids revealed
      that receptor binding is highly specific for 17,20beta-P, the likely maturation
      inducing steroid (MIS) in Arctic char. The relative-binding affinities of all the
      other progestogens and steroids tested were less than 5% of that of 17,20beta-P
      for the receptor. Several ortho, para derivatives of DDT also showed weak binding
      affinity for the 17,20beta-P receptor supporting the hypothesis that xenobiotics
      may bind steroid receptors on the oocyte's surface and might thereby interfere
      with oocyte growth and maturation.

PMID- 16281973
TI  - Zebrafish sex determination and differentiation: involvement of FTZ-F1 genes.
AB  - Sex determination is the process deciding the sex of a developing embryo. This is
      usually determined genetically; however it is a delicate process, which in many
      cases can be influenced by environmental factors. The mechanisms controlling
      zebrafish sex determination and differentiation are not known. To date no sex
      linked genes have been identified in zebrafish and no sex chromosomes have been
      identified. However, a number of genes, as presented here, have been linked to
      the process of sex determination or differentiation in zebrafish. The zebrafish
      FTZ-F1 genes are of central interest as they are involved in regulating
      interrenal development and thereby steroid biosynthesis, as well as that they
      show expression patterns congruent with reproductive tissue differentiation and
      function. Zebrafish can be sex reversed by exposure to estrogens, suggesting that
      the estrogen levels are crucial during sex differentiation. The Cyp19 gene
      product aromatase converts testosterone into 17 beta-estradiol, and when
      inhibited leads to male to female sex reversal. FTZ-F1 genes are strongly linked
      to steroid biosynthesis and the regulatory region of Cyp19 contains binding sites
      for FTZ-F1 genes, further linking FTZ-F1 to this process. The role of FTZ-F1 and
      other candidates for zebrafish sex determination and differentiation is in focus
      of this review.

PMID- 16281975
TI  - Decreased expression of cytochrome P450 protein in non-malignant colonic tissue
      of patients with colonic adenoma.
AB  - BACKGROUND: Cytochrome P450 (CYP) enzymes in epithelial cells lining the
      alimentary tract play an important role in both the elimination and activation of
      (pro-)carcinogens. To estimate the role of cytochrome P450 in carcinogenesis of
      the colon, expression patterns and protein levels of four representative CYPs
      (CYP2C, CYP2E1, CYP3A4 and CYP3A5) were determined in colon mucosa of normal and
      adenomatous colonic tissue of patients with adenomas and disease-free controls.
      METHODS: Expression of CYP2C, CYP2E1, CYP3A4, and CYP3A5 in colon mucosa of
      normal and adenomatous colonic tissue of patients with adenoma and disease-free
      controls was determined by RT-PCR. Protein concentration of CYPs was determined
      using Western blot. RESULTS: With the exception of CYP3A5, expression of CYP mRNA
      was similar among groups and tissues (e.g. normal colon mucosa and adenoma).
      CYP3A5 mRNA expression was significantly higher in adenoma in comparison to
      normal tissue of patients with adenoma (approximately 48%). When comparing
      protein concentrations of CYPs measured in adenomas with neighboring normal
      colonic mucosa no differences were found. However, in normal tissue of patients
      with adenomas, protein levels of CYP2C8, CYP3A4 and CYP3A5, but not that of
      CYP2E1, were significantly lower than in biopsies obtained from disease-free
      controls. Specifically, in normal colonic mucosa of patients protein
      concentrations of CYP2C8, CYP3A4, and CYP3A5 were approximately 86%,
      approximately 69%, and approximately 54%, respectively, lower than in disease
      free controls. CONCLUSION: In conclusion, among other factors, the altered
      protein levels of certain CYPs (e.g. CYP2C8, CYP3A4 and CYP3A5) in colon mucosa
      might contribute to the development of neoplasia in the colon.

PMID- 16281976
TI  - Geographic bias related to geocoding in epidemiologic studies.
AB  - BACKGROUND: This article describes geographic bias in GIS analyses with
      unrepresentative data owing to missing geocodes, using as an example a spatial
      analysis of prostate cancer incidence among whites and African Americans in
      Virginia, 1990-1999. Statistical tests for clustering were performed and such
      clusters mapped. The patterns of missing census tract identifiers for the cases
      were examined by generalized linear regression models. RESULTS: The county of
      residency for all cases was known, and 26,338 (74%) of these cases were geocoded
      successfully to census tracts. Cluster maps showed patterns that appeared
      markedly different, depending upon whether one used all cases or those geocoded
      to the census tract. Multivariate regression analysis showed that, in the most
      rural counties (where the missing data were concentrated), the percent of a
      county's population over age 64 and with less than a high school education were
      both independently associated with a higher percent of missing geocodes.
      CONCLUSION: We found statistically significant pattern differences resulting from
      spatially non-random differences in geocoding completeness across Virginia.
      Appropriate interpretation of maps, therefore, requires an understanding of this
      phenomenon, which we call "cartographic confounding."

PMID- 16281977
TI  - Cost-consciousness among Swiss doctors: a cross-sectional survey.
AB  - BACKGROUND: Knowing what influences physicians attitudes toward health care costs
      is an important matter, because most health care expenditures are the results of
      doctors' decisions. Many decisions regarding medical tests and treatments are
      influenced by factors other than the expected benefit to the patient, including
      the doctor's demographic characteristics and concerns about cost and income.
      METHODS: Doctors (n = 1184) in Geneva, Switzerland, answered questions about
      their cost-consciousness, practice patterns (medical specialty, public.vs.
      private sector, number of patients per week, time spent with a new patient), work
      satisfaction, and stress from uncertainty. General linear models were used to
      identify independent risk factors of higher cost-consciousness. RESULTS: Most
      doctors agreed that trying to contain costs was their responsibility ("agree" or
      "totally agree": 90%) and that they should take a more prominent role in limiting
      the use of unnecessary tests (92%); most disagreed that doctors are too busy to
      worry about costs (69%) and that the cost of health care is only important if the
      patient has to pay for it out-of-pocket (88%). In multivariate analyses, cost
      consciousness was higher among doctors in the public sector, those who saw fewer
      patients per week, who were most tolerant of uncertainty, and who were most
      satisfied with their work. CONCLUSION: Thus even in a setting with very high
      health care expenditures, doctors' stated cost-consciousness appeared to be
      generally high, even though it was not uniformly distributed among them.

PMID- 16281979
TI  - Prevalence and correlates of abscesses among a cohort of injection drug users.
AB  - Recent studies have indicated that injection-related infections such as abscesses
      and cellulitis account for the majority of emergency room visits and acute
      hospitalizations accrued by local injection drug users. The objective of this
      analysis was to examine the prevalence and correlates of developing an abscess
      among a cohort of injection drug users in Vancouver and to identify socio
      demographic and drug use variables associated with abscesses at baseline. We
      examined abscesses among participants enrolled in a prospective cohort of
      injection drug users. Categorical variables were analyzed using the Pearson's chi
      square test and continuous variables were analyzed using the Wilcoxon signed rank
      test. Among 1 585 baseline participants, 341 (21.5%) reported having an abscess
      in the last six months. In a logistic regression model that adjusted for all
      variables that were associated with having an abscess at p < 0.1 in univariate
      analyses, female gender [odds ratio (OR) = 1.7, [95% CI: 1.2 - 2.4]; p = 0.002),
      recent incarceration (OR = 1.7, [95% CI: 1.3 - 2.2]; p < 0.001), sex trade
      involvement (OR = 1.4 [95% CI: 1.0 - 2.0]; p = 0.03), frequent cocaine use (OR =
      1.5 [95% CI: 1.2 - 2.0]; p = 0.002) and HIV serostatus (OR = 1.5, [95% CI: 1.2 -
      2.0]; p = 0.003) were positively associated with having an abscess. Explanations
      for these associations require further study, and interventions are needed to
      address this highly prevalent concern.

PMID- 16281978
TI  - Application of protein lysate microarrays to molecular marker verification and
      quantification.
AB  - This study presents the development and application of protein lysate microarray
      (LMA) technology for verification of presence and quantification of human tissue
      samples for protein biomarkers. Sub-picogram range sensitivity has been achieved
      on LMA using a non-enzymatic protein detection methodology. Results from a set of
      quality control experiments are presented and demonstrate the high sensitivity
      and reproducibility of the LMA methodology. The optimized LMA methodology has
      been applied for verification of the presence and quantification of disease
      markers for atherosclerosis. LMA were used to measure lipoprotein [a] and
      apolipoprotein B100 in 52 carotid endarterectomy samples. The data generated by
      LMA were validated by ELISA using the same protein lysates. The correlations of
      protein amounts estimated by LMA and ELISA were highly significant, with r2 > or
      = 0.98 (p < or = 0.001) for lipoprotein [a] and with r2 > or = 0.94 (p < or =
      0.001) for apolipoprotein B100. This is the first report to compare data
      generated using proteins microarrays with ELISA, a standard technology for the
      verification of the presence of protein biomarkers. The sensitivity,
      reproducibility, and high-throughput quality of LMA technology make it a
      potentially powerful technology for profiling disease specific protein markers in
      clinical samples.

PMID- 16281980
TI  - Retroperitoneal myolipoma.
AB  - BACKGROUND: Myolipoma is a benign tumour in which smooth muscle cells are mixed
      with adipocytes. CASE PRESENTATION: A 34-year old lady presented with a mass in
      the right iliac fossa detected on computerised tomographic (CT) scan. Wide
      excision of the retroperitoneal mass was done. Histopathology showed features of
      myolipoma. There was no recurrence or metastasis at three years. CONCLUSION:
      Myolipoma is a rare benign entity; hence a benign course and good prognosis are
      expected.

PMID- 16281981
TI  - CD8+, HLA-unrestricted, cytotoxic T-lymphocyte line against malignant melanoma.
AB  - A CD8+ cytotoxic T lymphocyte (CTL) line was derived from the peripheral blood
      mononuclear cells of a patient with primary melanoma. The CD8+ CTL line
      specifically lysed the autologous primary melanoma cells and not the natural
      killer cell-sensitive K562 cells or lymphokine activated killer cell-sensitive
      DAUDI cells. When a large panel of human leukocyte antigen (HLA)-matched and 
      unmatched allogeneic melanoma, glioma, breast and colorectal carcinoma cells was
      tested as targets in cytolysis assays, 4 HLA-matched and two HLA-unmatched
      allogeneic metastatic melanoma lines were lysed by the CD8+ CTL. Lysis of
      autologous and allogeneic melanoma cells was dependent on the effector-to-target
      cell ratio. Lysis of autologous melanoma cells was not blocked by anti-HLA class
      I or class II antibodies, confirming that the cytolytic activity of the CD8+ CTL
      was HLA-unrestricted. CTL lysis of autologous melanoma cells was CD3 (T cell
      receptor) dependent and FAS-FAS-L, and CD1 independent. Identification of the
      melanoma-associated antigen recognized by the HLA-unrestricted CTL may provide a
      vaccine for a broad population of melanoma patients.

PMID- 16281982
TI  - Trading people versus trading time: what is the difference?
AB  - BACKGROUND: Person trade-off (PTO) elicitations yield different values than
      standard utility measures, such as time trade-off (TTO) elicitations. Some people
      believe this difference arises because the PTO captures the importance of
      distributive principles other than maximizing treatment benefits. We conducted a
      qualitative study to determine whether people mention considerations related to
      distributive principles other than QALY-maximization more often in PTO
      elicitations than in TTO elicitations and whether this could account for the
      empirical differences. METHODS: 64 members of the general public were randomized
      to one of three different face-to-face interviews, thinking aloud as they
      responded to TTO and PTO elicitations. Participants responded to a TTO followed
      by a PTO elicitation within contexts that compared either: 1) two life-saving
      treatments; 2) two cure treatments; or 3) a life-saving treatment versus a cure
      treatment. RESULTS: When people were asked to choose between life-saving
      treatments, non-maximizing principles were more common with the PTO than the TTO
      task. Only 5% of participants considered non-maximizing principles as they
      responded to the TTO elicitation compared to 68% of participants who did so when
      responding to the PTO elicitation. Non-maximizing principles that emerged
      included importance of equality of life and a desire to avoid discrimination.
      However, these principles were less common in the other two contexts. Regardless
      of context, though, participants were significantly more likely to respond from a
      societal perspective with the PTO compared to the TTO elicitation. CONCLUSION:
      When lives are at stake, within the context of a PTO elicitation, people are more
      likely to consider non-maximizing principles, including the importance of equal
      access to a life-saving treatment, avoiding prejudice or discrimination, and in
      rare cases giving treatment priority based purely on the position of being worse
      off.

PMID- 16281983
TI  - Preferential attachment in the evolution of metabolic networks.
AB  - BACKGROUND: Many biological networks show some characteristics of scale-free
      networks. Scale-free networks can evolve through preferential attachment where
      new nodes are preferentially attached to well connected nodes. In networks which
      have evolved through preferential attachment older nodes should have a higher
      average connectivity than younger nodes. Here we have investigated preferential
      attachment in the context of metabolic networks. RESULTS: The connectivities of
      the enzymes in the metabolic network of Escherichia coli were determined and
      representatives for these enzymes were located in 11 eukaryotes, 17 archaea and
      46 bacteria. E. coli enzymes which have representatives in eukaryotes have a
      higher average connectivity while enzymes which are represented only in the
      prokaryotes, and especially the enzymes only present in betagamma-proteobacteria,
      have lower connectivities than expected by chance. Interestingly, the enzymes
      which have been proposed as candidates for horizontal gene transfer have a higher
      average connectivity than the other enzymes. Furthermore, It was found that new
      edges are added to the highly connected enzymes at a faster rate than to enzymes
      with low connectivities which is consistent with preferential attachment.
      CONCLUSION: Here, we have found indications of preferential attachment in the
      metabolic network of E. coli. A possible biological explanation for preferential
      attachment growth of metabolic networks is that novel enzymes created through
      gene duplication maintain some of the compounds involved in the original
      reaction, throughout its future evolution. In addition, we found that enzymes
      which are candidates for horizontal gene transfer have a higher average
      connectivity than other enzymes. This indicates that while new enzymes are
      attached preferentially to highly connected enzymes, these highly connected
      enzymes have sometimes been introduced into the E. coli genome by horizontal gene
      transfer. We speculate that E. coli has adjusted its metabolic network to a
      changing environment by replacing the relatively central enzymes for better
      adapted orthologs from other prokaryotic species.

PMID- 16281984
TI  - Evolution of virulence: coinfection and propagule production in spore-producing
      parasites.
AB  - BACKGROUND: The evolution of within-host growth rates by parasites is expected to
      depend on a trade-off between propagule production and virulence. The presence of
      coinfections, however, is thought to alter this trade-off, and hence alter the
      evolutionarily stable strategy (ESS) for the parasite. Here I consider a model
      wherein the number of coinfections that are identical by descent can depend on
      the parasite's reproductive strategy. Transmission success was treated as being
      either a negative-linear or a negative-exponential function of the total number
      of propagules produced by all coinfections. RESULTS: Increasing the number of
      unrelated coinfections either selected for a decrease in reproductive output by
      the parasite (linear case), or had no effect on the ESS (exponential case).
      Nonetheless, the total number of propagules produced within each host increased
      in both cases. Increasing the relatedness among coinfections, however, selected
      for reductions in parasite reproduction in both cases. CONCLUSION: Unrelated
      coinfection may increase overall parasite virulence, but the result stems from
      adding more infections rather than to more aggressive growth by the individual
      infections. However, all else being equal, if the coinfections are more related
      than expected by chance alone, then the total reproductive output by all
      coinfections would be expected to be reduced, resulting in reduced virulence.

PMID- 16281985
TI  - Increased risk of cancer among relatives of patients with lung cancer in China.
AB  - BACKGROUND: Genetic factors were considered as one of the risk factors for lung
      cancer or other cancers. The aim of this work was to determine whether a genetic
      predisposition accounts for such familial aggregation of cancer among relatives
      of lung cancer probands. METHODS: A case-control study was conducted in 800 case
      families identified by lung cancer patients (probands), and in 800 control
      families identified by the probands'spouses. The data were analysed with logistic
      regression analysis model. RESULTS: The data revealed a significantly greater
      overall risk of cancer (OR = 1.82, P < 0.01) in the proband group. The relatives
      of lung cancer probands maintained an increased risk of non-lung cancer (P <
      0.05) after adjusting for confounder factors. The crude odds ratio of a proband
      family having one family member with cancer was 1.67 compared with control
      families. Proband families were 2.56 times more likely to have two other family
      members with cancer. For three cancers and four or more cancers, the risk
      increased to 3.50 and 5.91, respectively. The most striking differences in cancer
      prevalence between proband and control families were noted for cancer risk among
      female relatives. The strongest effects were for not only lung cancer in any
      female relatives (OR 2.17, 95%CI 1.60-3.64) and mothers (OR 2.78, 95%CI 1.23
      5.12) and sisters (OR 2.03, 95%CI 1.26-3.97), but also non-lung cancer in females
      and mothers (OR 2.00, 95%CI 1.26-3.01, and OR 2.34, 95%CI 1.28-4.40,
      respectively). CONCLUSION: These data support the hypothesis of a genetic
      susceptibility to cancer in families with lung cancer, and the female genetic
      susceptibility to cancer might be greater than male.

PMID- 16281986
TI  - Distinct types of glial cells populate the Drosophila antenna.
AB  - BACKGROUND: The development of nervous systems involves reciprocal interactions
      between neurons and glia. In the Drosophila olfactory system, peripheral glial
      cells arise from sensory lineages specified by the basic helix-loop-helix
      transcription factor, Atonal. These glia wrap around the developing olfactory
      axons early during development and pattern the three distinct fascicles as they
      exit the antenna. In the moth Manduca sexta, an additional set of central glia
      migrate to the base of the antennal nerve where axons sort to their glomerular
      targets. In this work, we have investigated whether similar types of cells exist
      in the Drosophila antenna. RESULTS: We have used different P(Gal4) lines to drive
      Green Fluorescent Protein (GFP) in distinct populations of cells within the
      Drosophila antenna. Mz317::GFP, a marker for cell body and perineural glia,
      labels the majority of peripheral glia. An additional approximately 30 glial
      cells detected by GH146::GFP do not derive from any of the sensory lineages and
      appear to migrate into the antenna from the brain. Their appearance in the third
      antennal segment is regulated by normal function of the Epidermal Growth Factor
      receptor and small GTPases. We denote these distinct populations of cells as
      Mz317-glia and GH146-glia respectively. In the adult, processes of GH146-glial
      cells ensheath the olfactory receptor neurons directly, while those of the Mz317
      glia form a peripheral layer. Ablation of GH146-glia does not result in any
      significant effects on the patterning of the olfactory receptor axons.
      CONCLUSION: We have demonstrated the presence of at least two distinct
      populations of glial cells within the Drosophila antenna. GH146-glial cells
      originate in the brain and migrate to the antenna along the newly formed
      olfactory axons. The number of cells populating the third segment of the antenna
      is regulated by signaling through the Epidermal Growth Factor receptor. These
      glia share several features of the sorting zone cells described in Manduca.

PMID- 16281988
TI  - Evasion of innate immunity by vaccinia virus.
AB  - Vaccinia virus, a member of the Poxviridae, expresses many proteins involved in
      immune evasion. In this review, we present a brief characterisation of the virus
      and its effects on host cells and discuss representative secreted and
      intracellular proteins expressed by vaccinia virus that are involved in
      modulation of innate immunity. These proteins target different aspects of the
      innate response by binding cytokines and interferons, inhibiting cytokine
      synthesis, opposing apoptosis or interfering with different signalling pathways,
      including those triggered by interferons and toll-like receptors.

PMID- 16281989
TI  - Subversion of host cell signalling by the protozoan parasite Leishmania.
AB  - The protozoa Leishmania spp. are obligate intracellular parasites that inhabit
      the macrophages of their host. Since macrophages are specialized for the
      identification and destruction of invading pathogens, both directly and by
      triggering an innate immune response, Leishmania have evolved a number of
      mechanisms for suppressing some critical macrophage activities. In this review,
      we discuss how various species of Leishmania distort the host macrophage's own
      signalling pathways to repress the expression of various cytokines and
      microbicidal molecules (nitric oxide and reactive oxygen species), and antigen
      presentation. In particular, we describe how MAP Kinase and JAK/STAT cascades are
      repressed, and intracellular Ca2+ and the activities of protein tyrosine
      phosphatases, in particular SHP-1, are elevated.

PMID- 16281990
TI  - Introduction to immune cell signalling.
AB  - The dynamic interaction of cells of the immune system with other cells, antigens
      and secreted factors determines the nature of an immune response. The response of
      individual cells is governed by the sequence of intracellular signalling events
      triggered following the association of cell surface molecules during cell-cell
      contact or the detection of soluble molecules of host or pathogen origin. In this
      review we will first outline the general principles of intracellular signal
      transduction. We will then describe the signalling pathways triggered following
      the recognition of antigen, as well as the detection of cytokines, and discuss
      how the signalling pathways activated regulate the effector response.

PMID- 16281991
TI  - Constitutively activated CK2 potentially plays a pivotal role in Theileria
      induced lymphocyte transformation.
AB  - Activation of casein kinase II (CK2) was one of the first observations made on
      how Theileria parasites manipulate host cell signal transduction pathways and we
      argue that CK2 induction may in fact contribute to many of the different
      activation events that have been described since 1993 for Theileria-infected
      lymphocytes such as sustained activation of transcription factors c-Myc and NF
      kappaB. CK2 also contributes to infected lymphocyte survival by inhibiting
      caspase activation and is probably behind constitutive PI3-K activation by
      phosphorylating PTEN. Finally, we also discuss how CK2A may act not only as a
      kinase, but also as a stimulatory subunit for the protein phosphatase PP2A, so
      dampening down the MEK/ERK and Akt/PKB pathways and for all these reasons we
      propose CK2 as a central player in Theileria-induced lymphocyte transformation.

PMID- 16281992
TI  - Stimulation of innate immune responses by malarial glycosylphosphatidylinositol
      via pattern recognition receptors.
AB  - The glycosylphosphatidylinositol (GPI) anchor of Plasmodium falciparum is thought
      to function as a critical toxin that contributes to severe malarial pathogenesis
      by eliciting the production of proinflammatory responses by the innate immune
      system of mammalian hosts. Analysis of the fine structure of P. falciparum GPI
      suggests a requirement for the presence of both core glycan and lipid moieties in
      the recognition and signalling of parasite glycolipids by host immune cells. It
      has been demonstrated that GPI anchors of various parasitic protozoa can mediate
      cellular immune responses via members of the Toll-like family of pattern
      recognition receptors (TLRs). Recent studies indicate that GPI anchors of P.
      falciparum and other protozoa are preferentially recognized by TLR-2, involving
      the MyD88-dependent activation of specific signalling pathways that mediate the
      production of proinflammatory cytokines and nitric oxide from host macrophages in
      vitro. However, the contribution of malaria GPI toxin to severe disease syndromes
      and the role of specific TLRs or other pattern recognition receptors in innate
      immunity in vivo is only just beginning to be characterized. A better
      understanding of the molecular mechanisms underlying severe malarial pathogenesis
      may yet lead to substantial new insights with important implications for the
      development of novel therapeutics for malaria treatment.

PMID- 16281993
TI  - Subversion of immune cell signal transduction pathways by the secreted filarial
      nematode product, ES-62.
AB  - Filarial nematodes achieve longevity within the infected host by suppressing and
      modulating the host immune response. To do this, the worms actively secrete
      products that have been demonstrated to possess immunomodulatory properties. In
      this article we discuss the immunomodulatory effects of the phosphorylcholine
      containing filarial nematode secreted glycoprotein ES-62. In particular we
      describe how it modulates intracellular signal transduction pathways in a number
      of different cells of the immune system, in particular B-lymphocytes, T
      lymphocytes, macrophages and dendritic cells.

PMID- 16281994
TI  - Arachidonic Acid-Induced COX-1 and COX-2-Mediated Vasodilation in Rat Gingival
      Arterioles In Vivo.
AB  - The roles of cyclooxygenase (COX) and prostaglandins (PGs) in the regulation of
      vasoreactivity of rat gingival arterioles in vivo were evaluated by sing an
      intravital microscope. The superfusion of indomethacin (a nonselective COX
      inhibitor) or SC-560 (a selective COX-1 inhibitor) onto the gingiva significantly
      constricted the arterioles, though NS-398 (a selective COX-2 inhibitor) did not
      affect the diameter of the arterioles. The SC-560-mediated constriction of the
      arterioles was completely reversed by an additional treatment with arachidonic
      acid (AA). The superfusion of AA, beraprost-Na (an analogue of PGI2) or PGE2 onto
      the gingival significantly dilated the arterioles dose-dependently. The AA
      induced dilation of the arterioles was significantly reduced by the treatment
      with SC-560 or NS-398. The expression of COX-1 and COX-2 were positive in the
      endothelium, but not the smooth muscles, of the arterioles. The expression of PGE
      synthase (PGES) was found only in the smooth muscles, but not the endothelium, of
      the arterioles. Neither the endothelium nor the smooth muscles of the arterioles
      expressed PGI synthase (PGIS). These findings suggest that the COX-2-mediated PG
      cascade may collaborate with the COX-1 pathway in the regulation of arteriolar
      myogenic activity in rat gingiva in the case of the supply of a large amount of
      AA.

PMID- 16281996
TI  - Cutting the cake: allocation of NHS research and development funding.

PMID- 16281997
TI  - Somatic symptoms and depression: diagnostic confusion and clinical neglect.

PMID- 16281998
TI  - Randomised controlled trial of a lay-led self-management programme for
      Bangladeshi patients with chronic disease.
AB  - BACKGROUND: Reducing the impact of chronic disease in minority ethnic groups is
      an important public health challenge. Lay-led education may overcome cultural and
      language barriers that limit the effectiveness of professionally-led programmes.
      We report the first randomised trial of a lay-led self-management programme - the
      Chronic Disease Self-Management Programme (CDSMP) (Expert Patient Programme) - in
      a south Asian group. AIM: To determine the effectiveness of a culturally-adapted
      lay-led self-management programme for Bangladeshi adults with chronic disease.
      DESIGN OF STUDY: Randomised controlled trial. SETTING: Tower Hamlets, east
      London. METHOD: We recruited Bangladeshi adults with diabetes, cardiovascular
      disease, respiratory disease or arthritis from general practices and randomised
      them to the CDSMP or waiting-list control. Self-efficacy (primary outcome), self
      management behaviour, communication with clinician, depression scores, and
      healthcare use were assessed by blinded interviewer-administered questionnaires
      in Sylheti before randomisation and 4 months later. RESULTS: Of the 1363 people
      invited, 476 (34%) agreed to take part and 92% (439/476) of participants were
      followed up. The programme improved self-efficacy (difference: 0.67, 95%
      confidence interval [CI] = 0.08 to 1.25) and self-management behaviour (0.53; 95%
      CI = 0.01 to 1.06). In the 51% (121/238) of intervention participants attending
      three or more of the 6-weekly education sessions the programme led to greater
      improvements in self-efficacy (1.47; 95% CI = 0.50 to 1.82) and self-management
      behaviour (1.16; 95% CI = 0.50 to 1.82), and reduced HADS depression scores
      (0.64; 95% CI = 0.07 to 1.22). Communication and healthcare use were not
      significantly different between groups. The programme cost pound123 (181) per
      participant. CONCLUSION: A culturally-adapted CDSMP improves self-efficacy and
      self-care behaviour in Bangladeshi patients with chronic disease. Effects on
      health status were marginal. Benefits were limited by moderate uptake and
      attendance.

PMID- 16281999
TI  - The accuracy of the Framingham risk-score in different socioeconomic groups: a
      prospective study.
AB  - BACKGROUND: The primary prevention of cardiovascular disease involves using the
      Framingham risk score to identify high risk patients and then prescribe
      preventive treatments. AIM: To examine the performance of the Framingham risk
      score in different socioeconomic groups in a population with high rates of
      cardiovascular disease. DESIGN OF STUDY: A prospective study. SETTING: West of
      Scotland. METHOD: The observed 10-year cardiovascular disease and coronary heart
      disease mortality rates in 5626 men and 6678 women free from cardiovascular
      disease from the Renfrew/Paisley Study were compared with predicted rates,
      stratified by socioeconomic class and by area deprivation score. RESULTS: The
      ratio of predicted to observed cardiovascular mortality rate in the 12 304 men
      and women with complete risk factor information was 0.56 (95% confidence interval
      [CI] = 0.52 to 0.60), a relative underestimation of 44%. Cardiovascular disease
      mortality was underestimated by 48% in manual participants (predicted over
      observed = 0.52, 95% CI = 0.48 to 0.56) compared to 31% in the non-manual
      participants (predicted over observed = 0.69, 95% CI = 0.60 to 0.81, P = 0.0005).
      Underestimation was also worse in participants from deprived areas (P = 0.0017).
      Only 4.8% of individuals had a 10-year cardiovascular risk of >40% (equivalent to
      >30% 10-year coronary risk), and 81% of deaths occurred in the rest. If the
      Framingham score had been recalibrated for manual and non-manual members of this
      population, an additional 3611 individuals mainly from manual social classes
      would have reached the treatment threshold. CONCLUSION: Currently recommended
      risk scoring methods underestimate risk in socioeconomically deprived
      individuals. The likely consequence is that preventive treatments are less
      available to the most needy.

PMID- 16282001
TI  - Qualitative study of an educational intervention for GPs in the assessment and
      management of depression.
AB  - BACKGROUND: Previous research has not shown any significant health gain for
      patients as a result of providing education about depression for GPs. Reasons for
      this, however, are unclear. AIMS: To explore relationships between process and
      outcome in the setting of a randomised controlled trial of a complex educational
      intervention designed to provide GPs with training in the assessment and
      management of depression. DESIGN OF STUDY: Qualitative study utilising semi
      structured interviews. SETTING: General practice in the northwest of England.
      METHOD: Semi-structured interviews with 30 GPs in Liverpool and Manchester who
      participated in a randomised controlled trial. RESULTS: Three major barriers to
      the effectiveness of the intervention were identified: the lack of the GP's
      belief that he/she could have an impact on the outcome of depression, the
      appropriateness of the training, and the organisational context in which doctors
      had to implement what they had learned. CONCLUSION: Attitudes toward treating
      depression may need addressing at a much earlier point in medical education. If
      students are introduced to a biosocial model of depression at an early stage,
      they may feel more hopeful about their ability to intervene when faced with
      patients who exhibit significant degrees of functional disability in the context
      of apparently socially determined disorders. Postgraduate interventions should be
      tailored to the treatment of depression as a common chronic condition and be
      focused at the level of the organisation, not the individual practitioner.

PMID- 16282000
TI  - Deciding who gets treatment for depression and anxiety: a study of consecutive GP
      attenders.
AB  - BACKGROUND: Most research has focused on recognition by GPs of the common mental
      disorders: depression and anxiety. However, less is known about the factors that
      determine whether patients with those disorders that are recognised receive any
      active treatment. AIM: To investigate factors associated with receiving active
      treatment among consecutive attenders identified by GPs as having a common mental
      disorder. SETTING: Data were collected as part of a cluster randomised controlled
      trial in 30 general practices in the south of Bristol, UK, on the impact of
      mental health guidelines in primary care. METHOD: We studied 439 consecutive
      general practice attenders aged 16-64 years who were given a diagnosis of
      depression, anxiety, or chronic mixed anxiety and depression by their GP. The
      main outcome measure was the provision of any active treatment, whether
      pharmacological or psychological, for these disorders. Patient, GP, and practice
      level data, including sociodemographic, clinical, and administrative data were
      explored as predictors in a logistic regression model. Huber White variance
      estimates were used to account for hierarchical clustering. RESULTS: Of those
      patients identified as having a common mental disorder by the GP, 54% were
      offered active treatment. Higher symptom score, as measured by the General Health
      Questionnaire (GHQ) (odds ratio [OR] = 1.09; 95% confidence interval [CI] = 1.06
      to 1.13; P<0.001) and being male (OR = 1.54; 95% CI = 1.13 to 2.09; P = 0.006),
      were both associated with an increased likelihood of being offered active
      treatment. Patients with anxiety (OR = 0.24; 95% = CI 0.14 to 0.41; P<0.001), or
      chronic mixed anxiety/depression (OR = 0.41; 95% CI = 0.23 to 0.73; P = 0.003)
      were less likely to be offered active treatment than those considered to have
      depression. CONCLUSION: When deciding to offer active treatment for common mental
      disorders, GPs appear to be influenced by the severity of symptoms rather than
      their 'understandability' in relation to recent life stresses or the social
      context of distress. Further research is needed to investigate why men are more
      likely and those with an anxiety disorder less likely, to be offered active
      treatment.

PMID- 16282002
TI  - First myocardial infarction in a Dutch general practice population: trends in
      incidence from 1975-2003.
AB  - BACKGROUND: As morbidity registrations generally do not make distinct first and
      following myocardial infarctions, it is still unclear as to what extent the
      falling rates of myocardial infarctions are caused by lower incidences of first
      myocardial infarctions. AIM: To investigate the incidence of first myocardial
      infarctions in a general practice population. METHOD: Data were taken from the
      Continuous Morbidity Registration (CMR) Nijmegen, which has been collecting data
      from four general practices since 1971. For the 1975-2003 period, sex-specific
      and age-specific yearly incidence rates were obtained from the registration data
      of the CMR. Trends were studied with Poisson regression. RESULTS: During the
      study period, 827 patients with a first myocardial infarction were identified.
      The incidence of first myocardial infarctions has declined since 1986 to 2.1 per
      1000 for men and to 1.5 per 1000 for women. The average age of getting a first
      myocardial infarction increased with 3 years for men and slightly decreased for
      women. Since 1986, the incidence of sudden cardiac death from a first myocardial
      infarction has considerably declined for men and women to 0.9 and 0.7 per 1000
      respectively. CONCLUSION: A slight, significant, decline in incidence of first
      myocardial infarctions was found. From the mid eighties a mean annual decline of
      3.5% in death from first myocardial infarction was observed. Though the variance
      in rates of coronary heart diseases is not unambiguous, this may indicate an
      effect of primary prevention. The decline was more pronounced in men, with an
      increasing age of getting a first myocardial infarction.

PMID- 16282003
TI  - Sleep complaints among older general practice patients: association with
      depression.
AB  - This study aimed to determine the prevalence of subjective sleep difficulties
      among general practice patients aged 60 years and over and to investigate their
      association with depression (CES-D>or=16). Sixty-three per cent of the 1029
      participants reported experiencing sleep difficulties. Subjects who reported
      sleep problems were 3.7 times (95% confidence interval = 2.5 to 5.5) more likely
      to be depressed than those who did not (adjusted for age, sex, financial burden
      and perceived health). GPs should consider screening for the presence of
      depressive symptoms whenever older adults complain of sleep difficulties.

PMID- 16282004
TI  - Interventions to improve management of anxiety disorders in general practice: a
      systematic review.
AB  - BACKGROUND: Anxiety disorders are common in general practice and are associated
      with several problems regarding recognition and management. AIM: To
      systematically evaluate the effectiveness of interventions aimed at improving
      recognition, diagnosis, and management of patients with anxiety disorders. DESIGN
      OF STUDY: Systematic review. METHOD: MEDLINE, EMBASE, PsychINFO, and the Cochrane
      Clinical Trials' Register were searched up until 2003. Randomised controlled
      trials, controlled before/after trials, and interrupted time series for
      professional, organisational, financial, and regulatory interventions were
      eligible. Primary effect measures consisted of anxiety outcomes, diagnosis,
      prescription, and referral. Two reviewers independently made eligibility
      judgments: eight out of 563 articles were found to be eligible. Two reviewers
      participated independently in the quality assessment and data extraction process
      using a standardised form based on the Effective Practice and Organisation of
      Care checklist. Relative risks or standardised mean differences were calculated
      when possible. RESULTS: Four professional interventions and three organisational
      interventions were examined. In general, the professional interventions seemed to
      increase recognition, referral, and prescription as well as improving anxiety
      outcomes. Two out of three organisational interventions showed a positive effect
      on anxiety outcomes. The one study that took prescription into account showed no
      effect. CONCLUSIONS: The quality of care for patients with anxiety can be
      improved. A combination of professional and organisational interventions in which
      an external expert is introduced seems to be most promising. Additional research
      is nevertheless necessary to determine the exact effects of such interventions
      using patient effect measures, economic evaluations, and feasibility studies.

PMID- 16282006
TI  - Assisted suicide.

PMID- 16282009
TI  - Assisted suicide.

PMID- 16282010
TI  - Breakdown in communication.

PMID- 16282011
TI  - Low carbohydrate diets for diabetes control.

PMID- 16282012
TI  - Continuity of care versus speed of access.

PMID- 16282005
TI  - Educational and organisational interventions used to improve the management of
      hypertension in primary care: a systematic review.
AB  - BACKGROUND: The optimal way in which to organise and deliver care to patients
      with hypertension has not been clearly identified. AIM: To determine the
      effectiveness of educational and organisational strategies used to improve
      control of blood pressure. DESIGN OF STUDY: Systematic review of randomised
      controlled trials (RCTs). METHOD: Quantitative pooling of RCT data on patients
      with hypertension that evaluated the following interventions: (1) self
      monitoring, (2) educational interventions directed to the patient, (3)
      educational interventions directed to the health professional, (4) health
      professional (nurse or pharmacist) led care, (5) organizational interventions
      that aimed to improve the delivery of care, (6) appointment reminder systems.
      RESULTS: Fifty-six RCTs met our inclusion criteria. The methodological quality of
      included studies was variable. An organised system of regular review allied to
      vigorous antihypertensive drug therapy was shown to reduce blood pressure
      (weighted mean difference -8.2/-4.2mmHg, -11.7/-6.5mmHg, -10.6/-7.6mmHg for three
      strata of entry blood pressure) and all-cause mortality at 5 years follow-up
      (6.4% versus 7.8%, difference 1.4%) in a single large RCT (the Hypertension
      Detection and Follow-up study). Other interventions had variable effects. Self
      monitoring was associated with moderate net reduction in diastolic blood
      pressure, weighted mean difference (WMD): -2.03 mmHg, 95% confidence interval
      (CI) = -2.7 to -1.4 mmHg. Educational interventions directed towards physicians
      were associated with small reductions in systolic blood pressure (WMD) -2.0mmHg,
      95% CI = -3.5 to -0.6mmHg and diastolic blood pressure (WMD) -0.4mmHg, 95% CI 
      1.1 to 0.3mmHg. CONCLUSIONS: General practices and community-based clinics need
      to have an organised system of regular follow-up and review of their hypertensive
      patients. Antihypertensive drug therapy should be implemented by means of a
      vigorous stepped care approach when patients do not reach target blood pressure
      levels. These findings have important implications for recommendations concerning
      implementation of structured delivery of care in hypertension guidelines.

PMID- 16282013
TI  - Breakdown in communication.

PMID- 16282015
TI  - Medical benefits.

PMID- 16282016
TI  - Good night, sleep tight, don't let the bed bugs bite.

PMID- 16282017
TI  - Big charity in New Orleans.

PMID- 16282020
TI  - Leave the kids alone.

PMID- 16282021
TI  - Total quality madness?

PMID- 16282028
TI  - NSAIDs and fracture healing: what's the evidence?

PMID- 16282029
TI  - Current concepts in the evaluation and management of stress fractures.
AB  - Although new technologies aid in making a rapid diagnosis and help predict
      clinical course of treatment, the diagnosis of stress fractures remains dependent
      on a high index of suspicion. Management of stress fractures involves clinical
      knowledge of those stress fractures that are prone to complication. The
      identification of predisposing factors to stress injury should be addressed.
      These include proper nutrition, hormonal balance, and correcting biomechanical
      deficits and training errors. Comprehensive evaluation and treatment is essential
      in facilitating recovery from stress fracture. Several new and more aggressive
      prevention and treatment strategies have been reported. The maintenance of
      cardiovascular fitness throughout the recovery process remains a key to the
      fastest return to full participation.

PMID- 16282030
TI  - Sideline management of asthma.
AB  - The timely, efficient, and effective sideline management of asthma must be based
      on an understanding of the disease processes, awareness of evidence-based
      therapeutic intervention, and thorough knowledge of the individual athlete's past
      and present medical history. There is accumulating evidence that exercise-induced
      airway narrowing, if unrecognized or inadequately treated, can progress to a
      severe life-threatening status and should always be viewed as a potential medical
      emergency. A widening range of therapeutic measures is currently available to
      prevent and treat exercise asthma, and treatment must be tailored to the
      individual circumstances in order to optimize response.

PMID- 16282031
TI  - Strength training: what the team physician needs to know.
AB  - Strength training has become an integral part of preparing for and participating
      in sports. Strength is one of the four components of athleticism, along with
      power, speed, and agility. Optimal strength training and conditioning workouts
      are best directed by a coach with formal training in this discipline.
      Unfortunately, many high school and some college programs do not have access to
      certified strength and conditioning coaches. This task often falls to the
      individual sport coaches and medical staff (athletic trainers and physicians). In
      this article we present a framework for practical strength training knowledge
      including the concepts of specificity, prioritization, periodization, and
      progressive overload. We also discuss concepts of the sports medicine team and
      its approach to training and conditioning. This framework will give physicians
      and other athletic heath care providers the basic information needed to design
      and implement a safe and effective strength training program.

PMID- 16282032
TI  - Exertional heat stroke in competitive athletes.
AB  - Exertional heat stroke (EHS) is a serious medical condition that can have a
      tragic outcome if proper assessment and treatment are not initiated rapidly. This
      article focuses on critical misconceptions that pertain to the prevention,
      recognition, and treatment of EHS, including 1) the randomness of EHS cases, 2)
      the role of nutritional supplements in EHS, 3) temperature assessment, 4) onset
      of EHS and the possible lucid interval, 5) rapid cooling, and 6) return to play.
      Exploration of these topics will enhance the medical care regarding EHS.

PMID- 16282033
TI  - Osteoporosis in a female cross-country runner with femoral neck stress fracture.

PMID- 16282034
TI  - Stress fractures in the female athlete.
AB  - Stress fractures are common among female athletes, especially runners. Although
      both intrinsic and extrinsic factors can contribute to stress injury etiology,
      the female athlete triad--negative energy balance leading to menstrual
      irregularity, and reduced bone mineral mass--is a significant contributor to the
      incidence of stress fractures in the female athlete. When combined with impact
      weight-bearing activity, this triad puts these women at increased risk for stress
      fractures. Treatment must focus on reversing identified risk factors, in addition
      to relative rest, and maintenance of fitness. Most stress fractures heal without
      complication. High-risk stress fractures should be evaluated and treated by a
      practitioner with expertise in the care of these injuries.

PMID- 16282035
TI  - Musculoskeletal injuries in the pediatric and adolescent athlete.
AB  - There are approximately 35 million children participating in organized sports in
      the United States. With this increasing participation, we have seen an overall
      increase in sports-related injuries in young athletes over the past 20 years.
      Young athletes suffer both acute and chronic, or overuse, injuries. They are
      susceptible to many of the same injuries as their adult counterparts, but due to
      the effects of growth on the musculoskeletal system, they are at risk for
      injuries to the growth plate, apophysis, and joint surface. Common acute and
      overuse injuries seen in young athletes are discussed here.

PMID- 16282036
TI  - Issues unique to the masters athlete.
AB  - As our population ages, promotion of physical activity as a tool to prevent and
      treat disease will become increasingly important. A number of physiologic changes
      occur with aging that may impact athletic performance, including decrease in
      muscle mass, decrease in maximum heart rate, and decrease in VO2max. These
      changes are not completely age-related, however, and losses are diminished with
      continued physical training. Exercise modestly improves bone density, improves
      function in osteoarthritis, and is vital for patients with coronary artery
      disease. Preparticipation evaluation should include screening for cardiovascular
      disease in high-risk populations. Very few contraindications for exercise in the
      elderly exist. Exercise in the older population is safe, healthy, and should be
      encouraged.

PMID- 16282037
TI  - Anterior cruciate ligament tear prevention in the female athlete.
AB  - This paper examines the effectiveness of implementing neuromuscular and
      proprioceptive training programs in female athletes and their ability to decrease
      the incidence of anterior cruciate ligament (ACL) injury. The relationship of
      sex, age, and training on the incidence of ACL injury is pivotal in developing a
      comprehensive neuromuscular and proprioceptive training program to decrease ACL
      injuries occurring in female athletes. Based on the 2-year results, ACL incidence
      has remained consistently lower in the intervention group versus the control
      group. A prophylactic neuromuscular and proprioceptive training program may have
      a direct benefit in decreasing the number of ACL injuries incurred by female
      athletes. This research foundation endorses further epidemiologic and biomechanic
      studies to determine the exact mechanism of ACL injury and the most effective
      intervention that will effectively decrease ACL injuries in this high-risk
      population.

PMID- 16282038
TI  - An update on nonsteroidal anti-inflammatory drugs and cyclooxygenase-2
      inhibitors.
AB  - Selective inhibitors of the cyclooxygenase-2 enzyme were developed to treat pain
      and inflammation while reducing the risk of the serious gastrointestinal side
      effects seen with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). The
      results of several clinical trials have demonstrated an apparent increased risk
      of serious cardiovascular events in patients taking the COX-2-selective
      inhibitors. Although the risk was observed originally with trials conducted with
      rofecoxib, it was attributed generally to the entire class of COX-2-selective
      drugs based on a similar mechanism of action and a hypothesis that predicted the
      possibility of a prothrombotic effect of the drugs compared with nonselective
      NSAIDs. Subsequent studies have demonstrated that elevated cardiovascular risk is
      not limited to the use of COX-2-specific inhibitors. An increase in
      cardiovascular risk actually has been seen with anti-inflammatory drugs of the
      NSAID class, regardless of whether they are selective or nonselective inhibitors.
      The US Food and Drug Administration has recommended that all such drugs carry a
      black box warning for gastrointestinal and cardiovascular risks.

PMID- 16282039
TI  - The use of opioids in the treatment of osteoarthritis: when, why, and how?
AB  - As life expectancy increases every decade, the incidence and prevalence of
      osteoarthritis (OA) also will increase. Despite progress in our knowledge of the
      pathophysiology of OA, the management of OA-mediated pain continues to challenge
      physicians. Concern regarding the cardiovascular effects of cyclooxygenase-2
      inhibitors and the gastrointestinal and renal side effects of nonsteroidal anti
      inflammatory drugs (NSAIDs) in general has limited the use of these medications
      in the management of chronic non-cancer pain. Appropriately dosed and monitored
      use of opioids for OA pain, when more conservative methods have failed, has
      potentially fewer life-threatening complications associated with it than the more
      commonly and often less successfully employed pharmacotherapeutic approaches to
      care. When used as part of a multimodal approach to pain control, opioids are a
      safe and effective treatment for joint pain, including that of OA. Patients for
      whom NSAIDs are contraindicated, or for whom combined acetaminophen, tramadol,
      and NSAID therapy is ineffective, may be started on low-dose opioids and titrated
      as needed and tolerated. Patient education and informed consent, exercise,
      complementary medicine, and the use of a controlled substance agreement increases
      the likelihood of patient compliance with treatment guidelines, improving
      functional capacity and quality of life.

PMID- 16282040
TI  - Fibromyalgia: progress in diagnosis and treatment.
AB  - Fibromyalgia is a frequent cause of chronic widespread pain and affects up to 5%
      of the general population. Diagnosis and treatment have been especially
      challenging due to limited knowledge of etiology and poor response to
      conventional treatment of pain. Appreciation for the interactions of
      neurobiologic, psychologic, and behavioral factors in the disease pathogenesis
      has led to improved treatment options that can be effective in individual
      patients. Current evidence advocates a multifaceted program emphasizing patient
      education, medications for improving symptoms, and aggressive use of exercise and
      cognitive-behavioral approaches to retain or restore function.

PMID- 16282041
TI  - Targeting cytokines beyond tumor necrosis factor-alpha and interleukin-1 in
      rheumatoid arthritis.
AB  - Targeting tumor necrosis factor-a has proven of considerable value in treatment
      for rheumatoid arthritis, with substantial benefits achieved in a proportion of
      treated patients. However, a significant number of patients do not achieve
      sufficient improvement and as a result there remains considerable unmet clinical
      need. A number of cytokines have recently been described with proinflammatory
      activity in rheumatoid arthritis synovitis, including interleukin (IL)-6, IL-12,
      IL-15, and IL-18. We review recent data that support the notion that some or all
      of these moieties offer therapeutic potential. The possibility that some may be
      useful in partial responders to tumor necrosis factor blocking agents or in
      synergy with the latter is discussed.

PMID- 16282043
TI  - Tension-type headache: classification and diagnosis.
AB  - Tension-type headache (TTH) is the most prevalent form of primary headache in the
      general population. In this article, the diagnostic challenges of TTH are
      discussed. The classification of these headaches according to the second edition
      of the International Classification of Headache Disorders (ICHD-2) and the main
      differences between the ICHD-2 and the first edition of the classification (ICHD
      1, 1988) are discussed. The typical features of TTH also are highlighted.
      Finally, the differential diagnosis of episodic and chronic TTH, emphasizing the
      situations more likely to raise doubts, is discussed. The wide clinical spectrum
      of TTH frequently challenges the physician's diagnostic acumen. A structured
      approach to the patient and a better comprehension of this variability of
      presentation should translate into better quality of care and a more specific
      diagnosis for TTH sufferers.

PMID- 16282042
TI  - Pathophysiology of tension-type headache.
AB  - Tension-type headache is one of the most common primary headache disorders.
      Advances in basic pain and clinical research have improved our understanding of
      pathophysiologic mechanisms of tension-type headache. Increased excitability of
      the central nervous system generated by repetitive and sustained pericranial
      myofascial input may be responsible for the transformation of episodic tension
      type headache into the chronic form. Studies of nitric oxide (NO) mechanisms
      suggest that NO may play a key role in the pathophysiology of tension-type
      headache and that the antinociceptive effect of nitric oxide synthase inhibitors
      may become a novel principle in the future treatment of chronic headache. Future
      studies should focus on investigation of the source of peripheral nociception,
      the role of descending pain modulation, and the development of an animal model of
      tension-type headache to support the pathophysiologic importance of central
      sensitization in tension-type headache.

PMID- 16282044
TI  - Medication-overuse headache.
AB  - Medication-overuse headache (MOH) can be caused by almost all anti-headache drugs
      including analgesics, ergots, triptans, and combined preparations The prevalence
      of chronic daily headache (CDH) appears to be between 2% and 4% in the general
      population. Current epidemiologic studies suggest that MOH accounts for
      approximately 50% of these cases. The pathophysiology of MOH remains unclear. The
      only therapy is withdrawal from the overused substances. Prednisone decreases the
      duration of headache in the first days of withdrawal therapy. The only strategy
      to reduce the prevalence of MOH is to prevent the development of MOH in the first
      place by restriction of anti-headache drugs and constant education of patients.

PMID- 16282045
TI  - The long-term prognosis of tension-type headache.
AB  - Tension-type headache (TTH) is a very common problem that usually causes only
      minimal to moderate discomfort and little disability. If episodic TTH evolves to
      chronic TTH, then the morbidity in terms of discomfort, disability, and use of
      medication escalates dramatically. There are no long-term studies, but inferences
      can be made from population surveys. These suggest that episodic TTH occurs in
      15% to 75% of the population, but 30% to 40% is the most common estimate. There
      is a modest increase in prevalence between the ages of 30 and 50 years and a
      decrease to 25% to 35% prevalence after the age of 60 years. TTH appears to
      remain a problem for most sufferers throughout their lives.

PMID- 16282047
TI  - [Evaluating the effects of acupuncture on knee osteoarthritis: a stepwise
      approach to research, University of Maryland experience].
AB  - Conventional treatments for osteoarthritis (OA), the most common form of
      arthritis, are associated with unpleasant adverse effects and often ineffective.
      Acupuncture and traditional Chinese medicine (TCM) have been used for thousands
      of years to treat pain and other dysfunctions. However, the scientific evidence
      on the efficacy of acupuncture and TCM is equivocal, and adapting the Western
      biomedical model to assess them is a great challenge. By adopting a systematic,
      step-by-step approach, the research team at the University of Maryland has been
      carefully evaluating the effectiveness of acupuncture on knee OA over the past 10
      years. Their successful experience may be a useful model for future acupuncture
      and TCM research.

PMID- 16282046
TI  - Pharmacoprophylaxis of tension-type headache.
AB  - Although tension-type headache typically is not as disabling as migraine, its
      chronic form may significantly impair patients' functional ability. The
      pathogenesis of tension-type headache remains largely unknown. Compared with
      migraine, tension-type headache is the object of much less research. For a number
      of years, research on headache therapy has vastly emphasized migraine. Even
      cluster headache, which is far less frequent than tension-type headache, has been
      subject to more therapeutic trials than tension-type headache. Therefore, it is
      not surprising that since the advent of studies (as early as 1964) on
      amitriptyline, which remains a pivotal treatment choice, the number of emerging
      treatments for this condition remains scarce, even in 2005. This emphasizes the
      need for renewed interest in this field. However, alternate treatment approaches,
      such as botulinum toxin injections, albeit controversial, have renewed hopes
      lately. In addition, recent progress in the understanding of tension-type
      headache pathophysiology, such as the role of peripheral and central
      sensitization, has revived interest in the field. This is a review of available,
      proven, or suspected prophylactic therapies for tension-type headache.

PMID- 16282048
TI  - [Possibility of applying nanotechnology to research on the basic theory of
      traditional Chinese medicine].
AB  - The ancient theory and technology which are related to preventive treatment of
      disease by dietetic regulation and coordinating meridian according to 25 tones
      have been developed in the early 21st century. It is proved in sonocytology by
      nanotechnology that cells are able to produce noise, and the noise will change at
      first when the cells have any disorders. This theory is in accordance with the
      one in Huangdi Neijing. The nanotechnology can be introduced into the basic
      research of traditional Chinese medicine and may contribute to the modernization
      of traditional Chinese medicine.

PMID- 16282049
TI  - [Chinese Tuina: challenge of evidence-based medicine and development strategy].
AB  - Evidence-based medicine (EBM), which aims to get the best evidence from medical
      research, is a growing international movement in health care. Because of this new
      shift in medical practice, great attention should be paid to how to introduce EBM
      into Chinese Tuina, and this is a good opportunity for the development of Chinese
      Tuina. To adopt EBM will be beneficial to developing Chinese Tuina, improving
      clinical research, renewing education mode and getting more academic achievement.
      So it is necessary to establish a new experimental methodology combined with EBM
      in order to get great progress in Chinese Tuina.

PMID- 16282050
TI  - [Correlations of clinical symptoms and treatment efficacy in patients with
      rheumatoid arthritis treated with Chinese herbal drugs or Western medicine].
AB  - OBJECTIVE: To evaluate the correlations between clinical symptoms and treatment
      efficacy in patients with rheumatoid arthritis (RA). METHODS: Four hundred and
      thirteen patients were included in the clinical trial from 9 clinical centers.
      They were randomly divided into Western medicine-treated group with 204 cases and
      Chinese herbal drug-treated group with 209 cases. Eighteen clinical symptoms were
      evaluated before and after treatment. The Western medicine therapy included
      voltaren extended release tablets, methotrexate and sulfasalazine. The Chinese
      herbal drug therapy included glucosidorum Tripterygii totorum tablets and Yishen
      Juanbi Tablets combined with treatment based on syndrome differentiation. The
      American College of Rheumatology 20 (ACR20) was used as efficacy evaluation
      criteria. RESULTS: In the Chinese herbal drug-treated group, clinical symptoms
      such as arthralgia and tenderness of joints were positively correlated with the
      efficacy after 12-week treatment, while frequent urination at night was
      negatively correlated. In the same group, tenderness of joints and fever were
      positively correlated with the efficacy after 24-week treatment, while deep
      colored and turbid urine was negatively correlated. In the Western medicine
      treated group, tenderness of joints and thirst were positively correlated with
      the efficacy after 12-week treatment, while vertigo was negatively correlated.
      And in the same group, tenderness of joints was positively correlated with the
      efficacy after 24-week treatment, while heaviness of limbs was negatively
      correlated to the efficacy. The statistical results showed that the treatment
      efficacy was improved when the correlated symptoms were included in the
      indications. CONCLUSION: The treatment efficacy of RA is correlated with some
      symptoms, so further studies should proceed on these correlations in order to
      achieve better treatment outcome.

PMID- 16282051
TI  - [Study on relationship between polymorphism of apolipoprotein E gene and
      syndromes of phlegm and blood stasis in patients with coronary heart disease].
AB  - OBJECTIVE: To explore the relationship between polymorphism of apolipoprotein E
      (ApoE) exon 4 gene and different syndromes in patients with coronary heart
      disease (CHD). METHODS: Two hundred patients with CHD were divided into four
      groups according to syndrome differentiation, including syndrome of phlegm (PS),
      syndrome of blood stasis (BSS), syndrome of phlegm-blood stasis blocking (PBBS)
      and syndrome of non-phlegm and non-blood stasis (NPNBS). One hundred healthy
      volunteers were included in control group. Blood lipids were measured by routine
      examination. Total DNA of peripheral blood was extracted. ApoE genotypes were
      determined by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) technique. All data were analyzed by SAS software. RESULTS: (1)The
      occurrence rate of epsilon4 allele of ApoE in patients with CHD was 19.5%,
      significantly higher than 9.5% in the control group (P<0.05), and the E 3/4
      genotype was especially more frequent (P<0.01). (2) The levels of total
      cholesterol (TC), total triglycerides (TG) and low-density lipoprotein
      cholesterol (LDL-C) in patients with epsilon4 were higher than those in patients
      without epsilon4 (P<0.01). (3) The frequencies of epsilon4 allele and E3/4
      genotype in patients with PS were significantly higher than those in patients
      with BSS (P<0.05). CONCLUSION: ApoE epsilon4 allele, especially E3/4 genotype, is
      the risk factor of CHD. There is a relatively close relationship between patients
      with ApoE epsilon4 allele and PS. It may be one of the main susceptible genes in
      CHD patients with PS.

PMID- 16282052
TI  - [Clinical study on severe acute pancreatitis associated with hypoalbuminemia in
      early stage].
AB  - OBJECTIVE: To investigate the occurring mechanism and clinical characteristics of
      severe acute pancreatitis (SAP) associated with hypoalbuminemia in early stage
      and its influence on prognosis of SAP and the preventive and therapeutic
      management of this disease. METHODS: One hundred and thirty-eight cases diagnosed
      as SAP complicated by hypoalbuminemia in early stage were accepted in our
      hospital from August 1, 2003 to December 31, 2004, and they were divided into 2
      groups according to the level of plasma albumin: mild hypoalbuminemia (30 to 35
      g/L) group and severe hypoalbuminemia (<30 g/L) group. The complications in the
      early stage, related parameters, and the incidence rate of infection and
      mortality in the later stage were evaluated respectively. RESULTS: The incidence
      rates of renal dysfunction, shock, cardiovascular failure and gastrointestinal
      hemorrhage, the score of acute physiology and chronic health evaluation II
      (APACHE II ) and the frequencies of pulse and breath in the severe
      hypoalbuminemia group were all higher than those in the mild hypoalbuminemia
      group (P<0.05 or P<0.01). The differences of incidence rate of hepatic failure
      and the scores of Ranson and Balthazar CT between these two groups had no
      statistical significance (P>0.05). The incidence rate of infection and the
      mortality in the severe hypoalbuminemia group were higher than those in the mild
      hypoalbuminemia group (P<0.01) in the later stage of SAP. CONCLUSION:
      Hypoalbuminemia in the early stage can accelerate the deterioration in
      pathophysiology of SAP. The lower level of the plasma albumin is in the early
      stage, the more complications and the higher incidence rate of infection and
      mortality will be in the later stage. To relieve the extent of systemic
      inflammatory response syndrome (SIRS) and abundant supplement of albumin, amino
      acid and lipid in time may be crucial to prevent the occurrence and deterioration
      of hypoalbuminemia.

PMID- 16282053
TI  - [Immunological mechanism of exfoliative tongue fur in children with asthma].
AB  - OBJECTIVE: To explore the immunological mechanism of exfoliative tongue fur in
      children with asthma. METHODS: Thirty-nine children with asthma, twenty-eight
      children with repetitive respiratory tract infection (non-asthma) and eleven
      healthy children were divided into five groups, which were asthma with
      exfoliative fur or with non-exfoliative fur groups, non-asthma with exfoliative
      fur or with non-exfoliative fur groups and normal control group. The
      concentrations of keratin 13 and bcl-2 in cells exfoliated from tongue fur were
      detected by immunohistochemical method. The expression levels of blood cell
      chemokine receptor-3 (CCR-3) and CD4(+) were examined by flow cytometry, and the
      levels of serum cortisol and IgE were detected by radioimmunoassay. RESULTS: The
      levels of blood CD4(+) and CCR-3 of children with asthma and exfoliative fur were
      higher than those in the asthma with non-exfoliative fur group and the normal
      control group (P<0.05). The serum level of cortisol in the groups of asthma with
      exfoliative fur and non-asthma with exfoliative fur were lower than that in the
      other groups (P<0.05). The serum levels of IgE in asthma with exfoliative fur or
      with non-exfoliative fur groups were higher than that in the other groups
      (P<0.05). Concentrations of keratin 13 in the cells exfoliated from tongue fur in
      the groups of asthma or non-asthma with exfoliative fur were lower than that of
      the other groups (P<0.05). There was no significant difference of expression
      level of bcl-2 in the cells exfoliated from tongue fur among these five groups.
      CONCLUSION: There is a reasonably close relationship between the formation of
      exfoliative tongue fur and the immune system such as low level of serum cortisol
      and high levels of blood CD4(+) and CCR-3, which may all promote the formation of
      exfoliative fur. The disability of keratinization and apoptosis of epithelial
      cells of tongue may also be one cause for its formation.

PMID- 16282055
TI  - [Effects of liuwei dihuang pills on expressions of apoptosis-related genes bcl-2
      and Bax in pancreas of OLETF rats].
AB  - OBJECTIVE: To investigate the effects of Liuwei Dihuang Pills (LWDHP) on
      expressions of apoptosis-related genes bcl-2 and Bax in pancreas of OLETF rats.
      METHODS: Forty male OLETF rats were randomly divided into LWDHP-treated group and
      untreated group. Another ten male LETO rats were included in normal control
      group. OLETF rats in the LWDHP-treated group were given LWDHP (2.4 g.kg(-1).d(
      1)) orally since the age of 8 weeks and the rats in the other two groups were
      given distilled water orally. Body weights of rats were recorded weekly and blood
      glucose concentration was determined by oral glucose tolerance test (OGTT).
      Pancreas weights were recorded after rats were killed and the expression levels
      of bcl-2 mRNA and Bax mRNA were detected by reverse transcriptase-polymerase
      chain reaction (RT-PCR). RESULTS: In the LWDHP-treated group, the expression of
      bcl-2 mRNA in the pancreas of rats at the age of 40 weeks (1.25+/-0.07) was much
      higher than that in the untreated group (1.01+/-0.16), P<0.01. Bax mRNA level in
      the LWDHP-treated group (0.57+/-0.11) was obviously lower than that in the
      untreated group (1.18+/-0.28), P<0.01. There was no significant difference of
      pancreas-to-body weight ratios between the LWDHP-treated group and the untreated
      group. The ability of glucose tolerance was improved in the LWDHP-treated group.
      CONCLUSION: LWDHP can up-regulate the expression of bcl-2 and down-regulate the
      expression of Bax at transcription level, which maybe contribute to the anti
      apoptosis effects of LWDHP.

PMID- 16282054
TI  - [Effects of flavones extracted from Portulaca oleracea on ability of hypoxia
      tolerance in mice and its mechanism].
AB  - OBJECTIVE: To identify anti-hypoxia ingredients extracted from Portulaca oleracea
      and to find out the possible mechanism of its anti-hypoxia actions. METHODS:
      Seventy mice were randomly divided into seven groups which were untreated (normal
      saline), ginsenosides-treated, polysaccharide-treated, acidic components-treated,
      basic components-treated, alkaloids-treated and flavones-treated groups, and the
      ingredients of polysaccharide, acidic components, basic components, alkaloids and
      flavones were extracted from Portulaca olerace. The mice in each group were fed
      with corresponding ingredients for one week respectively. Then the survival time
      of mice in hypoxic conditions was observed. Another 90 mice were divided into 3
      groups: untreated (normal saline), ginsenosides-treated and flavones-treated
      groups. The mice in each of these 3 groups were divided into 3 subgroups
      according to 12-, 24- and 36-hour exposure to hypoxia (10% oxygen and 90%
      nitrogen), respectively. After exposure to hypoxia, the red blood cell count
      (RBC), hemoglobin (Hb) concentration and hematocrit (HCT) in mice were
      determined. The plasma erythropoietin (EPO) levels of mice were detected by
      enzyme-linked immunosorbent assay (ELISA) and the relative values of EPO mRNA in
      renal tissue and pallium of mice were determined by reverse transcriptase
      polymerase chain reaction (RT-PCR). RESULTS: The survival time of mice in hypoxic
      conditions in flavones-treated group was significantly longer than that in the
      untreated group. The RBC, Hb concentration, HCT, plasma EPO level and the
      relative values of EPO mRNA in renal tissue and pallium of mice were
      significantly higher in the flavones-treated group than those in the untreated
      group. CONCLUSION: The anti-hypoxia ingredients extracted from Portulaca oleracea
      are flavones and the anti-hypoxia effects may be obtained by improving the
      expression level of EPO and accelerating the generations of erythrocyte and Hb.

PMID- 16282056
TI  - [Protective effects of Salvia miltiorrhiza on rats with streptozotocin diabetes
      and its mechanism].
AB  - OBJECTIVE: To explore the effects of Salvia miltiorrhiza on renal morphology and
      renal function of rats with streptozotocin diabetes. METHODS: Thirty male Wistar
      rats were randomly divided into three groups, which were normal control group,
      untreated group and Salvia miltiorrhiza-treated group. Diabetic nephropathy was
      induced in rats of the last two groups by intraperitoneal injection of
      streptozotocin after unilateral nephrectomy. Then the rats in the normal control
      and untreated groups were fed with normal saline while those in the Salvia
      miltiorrhiza-treated group were fed Salvia miltiorrhiza preparation for 8 weeks.
      The glomerular volume (VG), kidney-to-body weight ratio (KW/BW), urinary albumin
      excretion rate (UAER) and creatinine clearance (Ccr) were observed. The
      expression levels of transforming growth factor-beta1 (TGF-beta1), connective
      tissue growth factor (CTGF), fibronectin (FN) and plasminogen activator inhibitor
      1 (PAI-1) were detected by real-time quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) at the end of the experiment. RESULTS: UAER,
      Ccr, VG and KW/BW ratio were significantly higher in the untreated group than
      those in the normal control group (P<0.05). The expression levels of TGF-beta1,
      CTGF, PAI-1 and FN in the untreated group were also significantly higher as
      compared with those in the normal control group (P<0.05). UAER, Ccr, VG, KW/BW
      ratio and the levels of TGF-beta1, CTGF, PAI-1 and FN in the Salvia miltiorrhiza
      treated group were obviously lower than those in the untreated group (P<0.05).
      CONCLUSION: Salvia miltiorrhiza can protect rats with streptozotocin diabetes
      from diabetic nephropathy by suppressing the over-expressions of TGF-beta1, CTGF,
      PAI-1 and FN in renal cortex.

PMID- 16282057
TI  - [Effect of ginseng fruit saponins on insulin sensitivity index in high fat-fed
      rats].
AB  - OBJECTIVE: To observe the effect of ginseng fruit saponins (GFS) on insulin
      sensitivity index in high fat-fed rats. METHODS: An animal model of insulin
      resistance was established by injecting low dose of streptozotocin (STZ) in high
      fat-fed rats. Effect of GFS on insulin sensitivity was detected with glucose
      infusion rate (GIR) by euglycemic hyperinsulinemic clamp technique. RESULTS: The
      level of fasting blood glucose and insulin in untreated group increased more
      significantly than that in normal control group (P<0.05, P<0.01), while the index
      of GIR decreased significantly (P<0.01). As compared with the untreated groupithe
      parameters of GFS-treated groups were improved significantly in a dosage
      dependent manner (P<0.05, P<0.01). CONCLUSION: GFS can improve experimental
      insulin resistance in rats.

PMID- 16282058
TI  - [Effects of yiqi huayu recipe and its decomposed formulas on apoptosis-related
      factors of anulus fibrosus cells in rats].
AB  - OBJECTIVE: To study the effects of Yiqi Huayu Recipe and its decomposed formulas
      medicated sera on expressions of bcl-2, Bax and caspase-8 of apoptotic anulus
      fibrosus cells in rats. METHODS: Immunohistochemical and integral optical density
      analytic methods were used to observe the effects of Yiqi Huayu Recipe-, Yiqi
      Recipe-, Huayu Recipe-medicated sera and insulin-like growth factor 1 (IGF-1) on
      the expressions of bcl-2, Bax and caspase-8 of apoptotic anulus fibrosus cells in
      rats induced by anti-Fas antibody. RESULTS: As compared with apoptosis group, bcl
      2 expression was higher, Bax and caspase-8 expressions were lower in Yiqi Huayu
      treated, Yiqi-treated, Huayu-treated and IGF-1 groups (P<0.01). As compared with
      Yiqi-treated group and Huayu-treated group, Bax expression was lower in Yiqi
      Huayu-treated group (P<0.05). CONCLUSION: Yiqi Huayu Recipe and its decomposed
      formulas can delay degeneration of the cervical intervertebral disc, which may be
      due to its action in regulating the expressions of bcl-2, Bax and caspase-8.

PMID- 16282059
TI  - [Protective effects of yanggan lidan granules on carbon tetrachloride-induced
      liver damage in mice].
AB  - OBJECTIVE: To observe the protective effects of Yanggan Lidan Granules (YGLDG) on
      carbon tetrachloride (CCl(4))-induced liver damage in mice and to find out its
      mechanism. METHODS: A model of chronic liver damage was established in mice by
      intraperitoneal injection of CCl(4). After three weeks, those model mice were
      treated with low-, medium-, high-dose YGLDG, Danning Tablets and bifendate
      respectively for four weeks. Then the levels of serum alanine aminotransferase
      (ALT) and aspartate aminotransferase (AST), as well as the contents of superoxide
      dismutase (SOD) and malondialdehyde (MDA) in liver tissues were detected.
      RESULTS: YGLDG could significantly reduce the levels of serum ALT and AST in
      model mice, and the content of MDA was obviously decreased while the content of
      SOD was increased in liver tissue. CONCLUSION: The therapeutic effect of YGLDG on
      mice with CCl(4)-induced liver damage is to relieve the seriousness of liver
      damage, and its mechanism may relate to reducing peroxidation activity in liver
      tissue.

PMID- 16282060
TI  - [Effects of sanqi qiancao recipe on hemorheological parameters of rabbits with
      copper intrauterine device].
AB  - OBJECTIVE: To explore the mechanism of Sanqi Qiancao Recipe (SQR) in treating
      metrorrhagia caused by copper intrauterine device (IUD) in rabbits and to provide
      experimental evidence for preventing and treating this disease. METHODS: Fifty
      six rabbits were randomly divided into seven groups, which were normal control
      group, sham-operation group, untreated group, indomethacin-treated group, low
      dose SQR-treated group, medium-dose SQR-treated group and high-dose SQR-treated
      group. Copper IUD insertion was operated in rabbits of the last five groups.
      Rabbits in the last four groups were treated orally with indomethacin and low-,
      medium- and high-dose SQR respectively for a week. Rabbits in the untreated
      group, normal control group and sham-operation group were given distilled water
      orally. Hematocrit, blood viscosity at low, medium and high shear rate, plasma
      viscosity and blood sedimentation were examined after treatment. RESULTS: The
      hematocrit, blood viscosity at low, medium and high shear rate and plasma
      viscosity were higher in the untreated group than those in the normal control
      group with significant differences (P<0.01) while those indexes in low-, medium-
      and high-dose SQR-treated groups were significantly lower than those in the
      untreated group (P<0.05 or P<0.01). CONCLUSION: SQR can lead to a decrease in
      blood viscosity and improve the blood flow, which may be one of the mechanisms of
      SQR in treating metrorrhagia after copper IUD insertion.

PMID- 16282061
TI  - [Experimental study on effects of shengmai injection: enhancing 5-FU anti-tumor
      efficacy and reducing its toxicity].
AB  - OBJECTIVE: To observe the effects of Shengmai Injection on enhancing efficacy and
      reducing toxicity of 5-fluorouracil (5-FU). METHODS: Fifty hepatoma 22 bearing
      mice were randomly divided into five groups: control group, 5-Fu group, Shengmai
      Injection (low, medium and high dose) combined with 5-FU groups. There were 10
      mice in each group. Mice in the five groups were injected introperitoneally the
      same amount of normal saline, 5-FU (20 mg.kg(-1).d(-1)) and Shengmai Injection
      (3.5 ml.kg(-1).d(-1), 7 ml.kg(-1).d(-1) and 14 ml.kg(-1).d(-1)) combined with 5
      FU respectively, once a day for 14 days. After that, all mice were killed and the
      tumor inhibiting rates, index of immunological function, liver and kidney
      function and the blood cells in the peripheral blood were observed. RESULTS: The
      tumor inhibiting rates were higher in each Shengmai Injection combined with 5-FU
      group than that in the 5-FU group (P<0.05). The levels of CD3, CD4, CD4/CD8, IgG,
      IgM in 5-FU group were lower (P<0.05), while those in the three Shengmai
      Injection combined with 5-FU groups were higher than those in the control group
      (P<0.05). The level of serum alanine aminotransferase (ALT) was higher and the
      WBC and PLT counts in the peripheral blood were lower in 5-FU group than those in
      the control group (P<0.05). But the levels of serum ALT in the three Shengmai
      Injection combined with 5-FU groups were consistent with that in the control
      group and the amounts of WBC decreased slightly. CONCLUSION: Shengmai Injection
      can enhance the anti-tumor effect of 5-FU. It can also improve the immunological
      function and reduce the adverse reactions of chemotherapy.

PMID- 16282063
TI  - [Clinical observation of bushen naqi huoxue granules in treating patients with
      chronic obstructive lung disease].

PMID- 16282062
TI  - [Growth-inhibiting effect of psoralen plus ultraviolet-A light therapy on K562
      cells].
AB  - OBJECTIVE: To observe the effects of psoralen plus ultraviolet-A light (PUVA) on
      K562 cells and the relative mechanism. METHODS: The effects of psoralen,
      ultraviolet-A light and PUVA on K562 cells were assayed by monotetrazolium test
      (MTT). DNA content was analyzed by flow cytometry (FCM). The apoptotic rates of
      K562 cells treated with 40 and 80 microg/ml psoralen for 24 and 48 hours were
      assayed by Annexin-V-FITC/PI reagent kit on FCM respectively. The ultrastructures
      of apoptotic cells were observed by a transmission electron microscope (TEM).
      RESULTS: Either single psoralen therapy or single ultraviolet-A irradiation had
      inhibiting effect on K562 cells. The inhibiting effect of PUVA on K562 cells was
      stronger than that of the single psoralen therapy or single ultraviolet-A light
      irradiation (P<0.05). Apoptotic peak (AP) was detected by FCM. TEM test showed
      that K562 cells treated with PUVA were smaller, having condensed cell nucleus,
      assembled chromatin, disintegrated nucleus body and the majority of the cells
      appeared to be apoptotic conformation. CONCLUSION: Psoralen has inhibiting effect
      on K562 cells, and the effect of PUVA is more significant. It is suggested that
      10 min irradiation and 40 microg/ml terminal concentration of psoralen be
      probably the best choice for PUVA. The inhibiting effect of PUVA is due to
      apoptosis.

PMID- 16282064
TI  - [Experience in clinical practice of doctrines in Huangdi Neijing: Part 1].

PMID- 16282065
TI  - [Professor SHI Yin-Yu's experience in treating osteoporosis].

PMID- 16282066
TI  - [Progress in research on the treatment of primary liver cancer with traditional
      Chinese medicine for activating blood to resolve stasis].

PMID- 16282067
TI  - [Progress in research on focal adhesion kinase signal transduction and cross
      talk].

PMID- 16282068
TI  - [On hypotaxis and parataxis in English translation of traditional Chinese
      medicine].

PMID- 16282069
TI  - [Brief discussion on English translation of the term "five elements" in
      traditional Chinese medicine].

PMID- 16282070
TI  - The evaluation of the JEWEL project: an innovative economic enhancement and HIV
      prevention intervention study targeting drug using women involved in
      prostitution.
AB  - The JEWEL (Jewellery Education for Women Empowering Their Lives) pilot study
      examined the efficacy of an economic empowerment and HIV prevention intervention
      targeting illicit drug-using women (n=50) who were involved in prostitution in
      Baltimore, Maryland. The intervention was comprised of six 2-hour sessions that
      taught HIV prevention risk reduction and the making, marketing and selling of
      jewellery. Bivariate comparisons examined behaviour change pre- and 3-months post
      intervention. The intervention's effect on the change in the number of sex trade
      partners from baseline to follow-up was explored with multiple linear regression.
      Participants were 62.0% African American, 5.0% were currently employed, and the
      median age was 39 years old (Inter Quartile Range [IQR]: 34-45). Women attended
      an average of six (IQR: 4.5-6.0) sessions. The women sold over $7,000 worth of
      jewellery in eleven sales. In comparing self-reported risk behaviours pre and 3
      month post intervention participation, we found significant reductions in:
      receiving drugs or money for sex (100% versus 71.0%, p<0.0005); the median number
      of sex trade partners per month (9 versus 3, p=0.02); daily drug use (76.0% vs.
      55.0%, p=0.003); the amount of money spent on drugs daily (US$52.57 versus
      US$46.71, p = 0.01); and daily crack use (27.3% versus 13.1.0%, p = 0.014). In
      the presence of other variables in a multivariate linear model, income from the
      jewelry sale was associated with a reduction in the number of sex trade partners
      at follow-up. The pilot indicated effectiveness of a novel, HIV prevention,
      economic enhancement intervention upon HIV sexual risk behaviours and drug
      utilization patterns.

PMID- 16282071
TI  - Programmes, resources, and needs of HIV-prevention nongovernmental organizations
      (NGOs) in Africa, Central/Eastern Europe and Central Asia, Latin America and the
      Caribbean.
AB  - This study assessed the programmes, resources, and needs of HIV-prevention
      nongovernmental organizations (NGOs) in 75 countries in Africa, Central/Eastern
      Europe and Central Asia, Latin America and the Caribbean. Multiple databases and
      expert recommendations were used to identify one major HIV-prevention NGO in the
      capital or a large city in each country, and in-depth interviews were conducted
      with each NGO Director. Most NGOs are carrying out their programmes with minimal
      funding and few regularly employed personnel. Most are highly dependent on
      international donors, but reliance on small grants with short funding periods
      limits programme development capacity. HIV-prevention activities varied by
      region, with African NGOs most likely to use peer education and community
      awareness events; Eastern European NGOs most likely to offer needle exchange;
      Latin American NGOs to have resource centres and offer risk reduction programmes;
      and Caribbean organizations to use mass education approaches. Across regions,
      NGOs most often targeted the general public and youth, although specialized at
      risk groups were the additional focus of attention in some regions. Limited
      funding, governmental indifference or opposition, AIDS stigma, and social
      discomfort discussing sex were often cited as barriers to new HIV-prevention
      programmes. NGOs are critical service providers. However, their funding,
      programmes, and resource capacities must be strengthened if NGOs are to realize
      their full potential in HIV prevention.

PMID- 16282072
TI  - A formative evaluation of the potential role of nurse practitioners in a central
      London HIV outpatient clinic.
AB  - In-house audit demonstrated that 49% (173/352) of patients attending routine HIV
      outpatient care are asymptomatic and have needs that could potentially be met by
      other health care professionals. We therefore evaluated the potential development
      and acceptability of nurse practitioner roles in contributing to HIV outpatient
      care. Data were collected through 26 consultation observations, 25 patient
      interviews, 2 patient focus groups, 22 provider interviews and 8 provider focus
      groups. Service users were key members of the evaluation team. With increasing
      HIV incidence and the change in focus of doctor-patient consultations from acute
      to chronic disease management, there are concerns about the sustainability of
      easily available routine HIV outpatient appointments using the same model of care
      that has prevailed over the past 20 years. Nurse practitioner models of care were
      considered acceptable for asymptomatic patients, including those who do not have
      complex issues related to highly active antiretroviral therapy (HAART). Key
      considerations for the role include training, supervision, referral pathways, and
      a clear understanding of the limitations of nursing practice. There is an
      emphasis on the need to consider 'new ways of working' throughout the service,
      rather than merely substituting or transferring clinical roles between
      professionals. Funding pending, nurse practitioner roles are planned for
      implementation in late 2004. Evaluation will determine impact on service
      utilization, health and economic outcomes.

PMID- 16282073
TI  - Narrowing sexual behavioural differences between Chinese and non-Chinese
      populations in Hong Kong: implications for sexually transmitted infection (STI)
      transmission.
AB  - Information on sexual networking between different ethnic groups, in particular
      between Chinese and non-Chinese, is scarce. This study compared patterns of
      sexual behaviour and determinants of unsafe sexual behaviours amongst the Chinese
      and non-Chinese residents of Hong Kong. Of the 2,060 respondents (2060/4157; 50%
      response rate), 73% identified themselves as being ethnic Chinese. Overall,
      having a non-regular partner was more common amongst the non-Chinese (36%) than
      the Chinese (17%) respondents. Chinese people who were at increased risk of
      having had sex with a non-regular partner included social hygiene clinic
      attendees and airport travellers, males and ever smokers. For non-Chinese this
      was inconsistent condom use and being aged 18-45. Predictors of inconsistent
      condom use for Chinese included being aged 18-45, never having been married, and
      having had sex with non-regular partners; for non-Chinese the predictors were
      being aged 18-45, having had sex with non-regular partners and being unafraid of
      AIDS. We conclude that there are similarities and differences in sexual risk
      taking behaviours between Chinese and non-Chinese residents in Hong Kong. To
      maximize potential public health benefits, behavioural interventions should be
      designed to address the different risk profiles of Chinese and non-Chinese
      populations separately.

PMID- 16282074
TI  - Long-term HIV/AIDS-related prevention behaviours among men having sex with men:
      Switzerland 1992-2000.
AB  - The aim of this paper is to present trends in reported HIV-related behaviours
      among men having sex with men (MSM) in Switzerland. In 1992, 1994, 1997 and 2000
      a standardized anonymous questionnaire was placed in gay newspapers and
      distributed in gay associations. High levels of protection (no anal sex or
      consistent condom use) with casual partners were found: around 90%, with a peak
      in 1994 and a slight decrease in 2000 to the level of 1992. With the steady
      partner, the level of protection was 57% in 1992, 61% in 1997 and decreased in
      2000 to the same level as in 1992. The proportion of couples with both HIV
      statuses known increased from 49% in 1994 to 59% in 2000. In 2000, 26% of
      concordant HIV negative couples protected themselves compared to 83% of those
      exposed to an actual or potential risk (HIV status discordant or unknown). Within
      each category of couples, there was no change over time in the level of reported
      practice of anal sex and condom use. This slight decrease in prevention behaviour
      justifies efforts to maintain HIV/AIDS prevention targeted at gay men.

PMID- 16282075
TI  - Sources of AIDS awareness among women in India.
AB  - Sources of AIDS awareness among rural and urban Indian women were analysed using
      data from the National Family and Health Survey (1998-2000). Two measures were
      developed to study the impact each source had on knowledge. 'Effectiveness' was
      defined as the proportion of women who had heard of AIDS from only one source,
      from among women who had heard of AIDS from that particular source and other
      sources. 'Independent effect' was the proportion who had heard of AIDS from only
      one source in relation to all women who had heard of AIDS. Television was the
      most effective medium, and also had the highest independent effect. Radio and
      print had very low effectiveness and independent effect. Although television and
      print audiences are growing in India, it is likely a sub-group of women will
      continue to lack media access. There is an urgent need to disseminate AIDS
      awareness to this 'media underclass'. Since the media will not reach this group,
      other sources including health workers, community level activities such as adult
      education programmes, and networks of friends and relatives need to be explored.

PMID- 16282076
TI  - Gender and race matching preferences for HIV post-test counselling in an African
      American sample.
AB  - This study tested whether having racially and gender-matched counsellors for HIV
      Post-test counselling were preferred. In the NIDA-funded EachOneTeachOne study,
      115 African American respondents (19-68) were asked would they rather talk to
      someone of the same sex and race. Forty-three percent of the counsellor
      respondent pairs were race concordant, and 58% were gender concordant. Chi-square
      statistics examined effects of gender, race and match. Out of those who desired a
      gender-match, 89% were men compared to 11% of women. Only 9% of African-Americans
      reported that they would feel more comfortable talking to an African-American
      counsellor. The sample size dropped due to non-response of the matching reference
      questions. Among the 39 race-counsellor concordant respondents (n=98), 23%
      expressed a preference for a race matched counsellor while no one with a race
      discordant counsellor expressed such a preference. Among the 56 respondents with
      a gender concordant counsellor (n=102), 27% said they would prefer a gender
      matched counsellor in the future; only 7% of those with a gender discordant
      counsellor expressed such as preference. Previously matched respondents were more
      likely to desire matched counsellors, but the majority still did not. Assumptions
      that race and gender matching are imperative are not supported by these findings.

PMID- 16282077
TI  - Cruising for sex: sexual risk behaviours and HIV testing of men who cruise,
      inside and outwith public sex environments (PSE).
AB  - This paper describes sexual risk behaviours and HIV testing amongst men who
      cruise an urban public sex environment (PSE) in southern England. Data were
      collated using a cross-sectional survey (response rate = 56%; n=216), sampling
      men from directly within the PSE. As such, this represents the first peer-review
      study generalizable to the wider population of urban PSE users. The current
      sample reflect a highly sexually active population, almost one-third (31%)
      reported over 50 sex partners in the last year. However, just one-quarter (26%)
      reported unprotected anal intercourse (UAI) with at least one partner outside of
      a 'safer sexual strategy'. Almost 1 in 12 (7%) reported UAI within the PSE. Over
      two-thirds (71%) had had a named HIV test of whom 16% had tested HIV positive.
      Just one-third (34%) of negative/untested PSE users had tested within the
      previous two years. Positive men were significantly more likely to report unsafe
      sex within the PSE in the last year. PSE users report lower levels of UAI than
      men in the local gay community but higher HIV prevalence. PSE-based UAI remains
      an HIV (re)infection risk. In concert, these findings suggest the importance of
      in situ targeted health promotion to prevent PSE-based risks.

PMID- 16282078
TI  - The role of stigma in reasons for HIV disclosure and non-disclosure to children.
AB  - This study examined how stigma may impact HIV-positive women's disclosure to
      their children. Participants included HIV-infected women recruited from AIDS
      service organizations located in large midwestern cities. Using a questionnaire
      and guided interview, quantitative data were obtained regarding perceived HIV
      related stigma and rates of maternal disclosure to children aged 5-18. According
      to the Kruskal-Wallis test, comparison between the disclosure groups showed non
      significant differences in the total score of HIV stigma (chi(2)=0.518 with df =
      2, p=0.77).

PMID- 16282080
TI  - Listening to children and young people affected by parental HIV: findings from a
      Scottish study.
AB  - This study, conducted between 1999 and 2002, set out to explore the experiences
      of children and young people in Scotland with a parent or carer with HIV. The
      study had three elements: a postal survey of health and social work agencies,
      interviews with twenty-eight children and young people and a postal survey of
      schools. The study found little recognition from statutory agencies of the needs
      of affected children, whether in health, education or social work. Moreover, the
      children and young people who took part in the study bore a heavy burden in terms
      of stigma, family disruption and loss. Nevertheless, their greatest wish was to
      be seen as 'normal' children with 'normal' parents.

PMID- 16282079
TI  - Knowledge and attitudes regarding preventative HIV vaccine clinical trials in
      Italy: results of a national survey.
AB  - We carried out a telephone survey to assess willingness to participate in HIV
      vaccine trials. The survey was conducted by interviewing randomly selected
      callers to the Italian National AIDS Help line. The questionnaire consisted of
      four sections: demographic information, knowledge about HIV vaccines and vaccines
      in general, factors related to participation in HIV vaccine trials, and
      acceptability of a future HIV vaccine. Over 50% of the sample had adequate
      knowledge about HIV and vaccines. Among the individuals interviewed, 37% would
      volunteer for a vaccine trial; those reporting high-risk behaviours were more
      likely to volunteer. Of the participants, 83% would agree to be vaccinated with a
      highly effective vaccine, and 92% would pay for the vaccine. Although the limits
      of telephone surveys should not be neglected, the results of this survey are
      encouraging.

PMID- 16282081
TI  - Results of the Expanded HIV Risk Factor Assessment Project (EHRAP).
AB  - An objective of EHRAP was to evaluate the HIV risk factor information reported to
      CDC through routine surveillance. HIV/AIDS surveillance programmes used medical
      and ancillary records to determine if information on HIV risk factors can be
      found for surveillance. Surveillance staff from Mississippi, South Carolina, and
      Virginia collected data on risk factors for HIV infection on a sample of cases
      diagnosed during 1998 and 1999. Overall percent agreement and Cohen kappa
      statistics were calculated for initially reported compared to EHRAP-identified
      risk factors. Of 160 cases reported without an identified risk factor, 86% were
      reclassified with a known risk factor. A risk factor was identified for 96% of
      all cases of HIV infection. Overall, agreement was good (kappa = 0.89) between
      initially reported and verified HIV risk factor. All three states met the
      national goal of at least 85% of reported cases with a risk factor for HIV
      infection. The completeness of collection and reporting of HIV risk factors for
      national HIV/AIDS surveillance can be improved. The current method of risk factor
      redistribution at the national level should be evaluated.

PMID- 16282082
TI  - Prevailing discourses among AIDS care professionals about childbearing by couples
      with HIV in Taiwan.
AB  - The aim of this study was to analyze the dynamics of ideology, power and language
      in the dominant discourses about childbearing by couples with HIV that were
      expressed by AIDS care professionals in Taiwan. Critical discourse analysis of
      the interview texts with 11 AIDS care professionals identified three prevailing
      discourses on childbearing by couples with HIV/AIDS: pro-children, conditional
      pro-choice and pro-rights. The pro-children and conditional pro-choice were the
      predominant discourses. The two discourses both medicalized childbearing among
      couples with HIV/AIDS by identifying medical authorities as the proper persons to
      decide which reproductive choices people with HIV/AIDS should make under what
      conditions. Even though the pro-rights discourse embodied an ideology of
      individualism, empowerment and autonomy, it was weak and relatively rare in the
      other two discourses.

PMID- 16282084
TI  - Introduction to special issue "addiction pharmacotherapy and special
      populations".

PMID- 16282085
TI  - Medical illness and comorbidities in drug users: implications for addiction
      pharmacotherapy treatment.
AB  - Providing effective medical care to those with substance use disorders can be a
      challenge to clinicians. In this article, we briefly summarize issues that occur
      frequently in the medical treatment of substance users. The focus of this article
      is twofold. The first is to briefly summarize common co-occurring medical
      illnesses in those manifesting substance use disorders with an emphasis on issues
      related to providing effective treatment for these diseases in this population.
      Using specific examples of frequently occurring comorbid medical illness in
      substance users, including infectious diseases (hepatitis C and HIV disease),
      sexually transmitted diseases, and pregnancy as examples, the complexities of
      medical care for this population is demonstrated. Second, this article addresses
      some of the difficulties encountered in pharmacotherapy aimed specifically at
      treatment of substance use disorders. For example, difficulties in managing
      concomitant opiate therapy in those requiring medications for medical illness
      that may have strong and adverse interactions with opiates are addressed. Adverse
      events reported for some substance use disorder pharmacotherapies are also
      highlighted. We conclude with a brief review of models of care that have been
      effective in addressing the needs of this challenging population that can provide
      additional means for enhancing the clinical care of substance users.

PMID- 16282087
TI  - Addiction and the treatment of pain.
AB  - Persons experiencing pain, whether acute or chronic, seek and deserve relief from
      their discomfort and loss of function. However, opioid analgesics have the
      capacity to induce tolerance, physical dependence, and addiction. Furthermore,
      persons with a history of opioid use disorders or other substance misuse problems
      are at "high risk" when they acquire painful conditions requiring aggressive
      treatment. Prescription of opioids could trigger a relapse to the original drug
      of choice or could initiate a new bout of addiction with the prescribed drug.
      This article explores the relationship between addiction and pain, including
      signs of developing addiction and approaches to managing pain in those with
      addiction.

PMID- 16282088
TI  - Adult ADHD and substance abuse: diagnostic and treatment issues.
AB  - Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral,
      developmental disorder most often diagnosed during childhood, marked by the core
      symptoms of inattention, hyperactivity, and impulsivity that results in social,
      academic, and occupational underachievement. Although the disorder has a
      prevalence of 3-9% in the general childhood population and 1-5% in the general
      adult population, it affects between 11 and 35% of "substance-abusing" adults,
      oftentimes complicating treatment response. The present review discusses
      diagnostic assessment issues, prevalence, comorbidity, pharmacotherapy, and
      psychological interventions in substance-abusing adults with ADHD.

PMID- 16282086
TI  - Combination treatment for nicotine dependence: state of the science.
AB  - Both nicotine replacement and sustained-release buproprion double the odds of
      achieving short- and moderate-term abstinence from nicotine. However, questions
      remain about the efficacy of combining pharmacotherapies. Our purposes were to
      review the evidence for (1) combined pharmacotherapy and (2) multimodal treatment
      combining pharmacotherapy and behavioral treatment and to recommend combinations
      of treatments to reduce nicotine dependence. Combining first-line
      pharmacotherapies with each other or with investigational drugs shows little
      benefit. In contrast, trials combining specific behavioral treatments with first
      line pharmacotherapies show enhanced smoking cessation rates, but benefits are
      not seen in all populations. We recommend future directions for research,
      including better specification of behavioral components and further examination
      of the length and timing of treatment.

PMID- 16282089
TI  - Pharmacotherapy treatment in substance-dependent correctional populations: a
      review.
AB  - The number of drug or alcohol dependent inmates has increased dramatically in
      recent years. About half of all inmates meet DSM-IV criteria for dependence at
      the time of their arrest and require substance use treatment or detoxification.
      Few inmates receive treatment while in prison, increasing the likelihood that
      they will continue to use substances in prison and after release. While
      pharmacotherapy interventions have been shown to be effective with substance
      users in the community, few studies have investigated these treatments with a
      prison population. Further research is needed to better understand the
      feasibility and efficacy of providing pharmacotherapies for substance dependence
      disorders within this population.

PMID- 16282090
TI  - Pharmacotherapy of alcohol use disorders.
AB  - Therapeutic interventions to treat alcoholism have increased in number, including
      several pharmacotherapies. Aspects of epidemiology, gender, and psychiatric
      comorbidity as well as a brief overview of neurobiology are presented as an
      introduction. The medications used clinically for the treatment of alcoholism,
      disulfiram and naltrexone, approved by the Food and Drug Administration in the
      United States for the treatment of alcoholism and acamprosate, a medication used
      extensively in Europe that is currently being evaluated in the United States, are
      reviewed in detail. An overview of the serotonergic agents is also provided.
      Finally, future directions, including new medications and some clinical
      strategies that show promise but are not yet used extensively clinically, are
      mentioned.

PMID- 16282091
TI  - Pharmacotherapy of comorbid mood, anxiety, and substance use disorders.
AB  - Mood and anxiety disorders commonly co-occur with substance use disorders.
      Exploration of the neurobiology of substance use disorders and mood and anxiety
      disorders have found that the neural circuitry in mood, anxiety, and substance
      use disorders is clearly overlapping. These discoveries have encouraged the
      exploration of a number of pharmacotherapeutic agents in the treatment of co
      occurring mood, anxiety, and substance use disorders. In this article, recent
      data on the pharmacotherapeutic treatment of mood and anxiety disorders in
      individuals with substance use disorders are reviewed. Some of the barriers to
      the use of pharmacotherapy in individuals with substance use disorders are
      discussed.

PMID- 16282096
TI  - Coexisting commitments to ethics and human research: a preliminary study of the
      perspectives of 83 medical students.

PMID- 16282099
TI  - Reflections on the appointment of Dr. Edmund Pellegrino to the President's
      Council on Bioethics.

PMID- 16282100
TI  - Eggs, lies and compromise.

PMID- 16282101
TI  - Judging public health research: epistemology, public health and the law.

PMID- 16282102
TI  - Rescuing human embryonic stem cell research: the Blastocyst Transfer Method.
AB  - Despite the therapeutic potential of human embryonic stem (HES) cells, many
      people believe that HES cell research should be banned. The reason is that the
      present method of extracting HES cells involves the destruction of the embryo,
      which for many is the beginning of a person. This paper examines a number of
      compromise solutions such as parthenogenesis, the use of defective embryos,
      genetically creating a "pseudo embryo" that can never form a placenta, and
      determining embryo death, and argues that none of these proposals are likely to
      satisfy embryoists, that is, those who regard the embryo as a person. This paper
      then proposes a method of extracting HES cells, what might be called the
      Blastocyst Transfer Method, that meets the ethical requirements of embryoists,
      and it considers some possible concerns regarding this method. It concludes by
      encouraging future HES cell research to investigate this method.

PMID- 16282103
TI  - Embryological viability.

PMID- 16282104
TI  - Blastocyst transfer (sic) is no solution.

PMID- 16282105
TI  - The Blastocyst Transfer Method cannot rescue Human Embryonic Stem cell research.

PMID- 16282106
TI  - Obtaining stem cells: moving from Scylla toward Charybdis.

PMID- 16282107
TI  - What qualifies as a live embryo?

PMID- 16282108
TI  - "Embryo autonomy?" What about the autonomy of infertility patients.

PMID- 16282109
TI  - Can we really bypass the moral debate for embryo research?

PMID- 16282110
TI  - Stem cells and the blastocyst transfer method: some concerns regarding autonomy.

PMID- 16282111
TI  - Three stages in the lifecycle of bioethics: observations on "bioethics as co-PI".

PMID- 16282112
TI  - Confronting deep moral disagreement: the President's Council on Bioethics, moral
      status, and human embryos.
AB  - The report of the President's Council on Bioethics, Human Cloning and Human
      Dignity, addresses the central ethical, political, and policy issue in human
      embryonic stem cell research: the moral status of extracorporeal human embryos.
      The Council members were in sharp disagreement on this issue and essentially
      failed to adequately engage and respectfully acknowledge each others' deepest
      moral concerns, despite their stated commitment to do so. This essay provides a
      detailed critique of the two extreme views on the Council (i.e., embryos have
      full moral status or they have none at all) and then gives theoretical grounding
      for our judgment about the intermediate moral status of embryos. It also supplies
      an account of how to address profound moral disagreements in the public arena,
      especially by way of constructing a middle ground that deliberately pays sincere
      respect to the views of those with whom it has deep disagreements.

PMID- 16282113
TI  - The moral status of the early human embryo: is a via media possible?

PMID- 16282114
TI  - Toward a full theory of moral status.

PMID- 16282115
TI  - Ethical justifications for moratoriums on vanguard scientific research.

PMID- 16282116
TI  - Contexts, anyone? The need for contextualization in the debate about the moral
      status of embryos.

PMID- 16282117
TI  - The public's role in science policy.

PMID- 16282118
TI  - The disposer's dilemma.

PMID- 16282119
TI  - Deep disagreement and Rawlsian "public reasons".

PMID- 16282120
TI  - Deep disagreement, respect, and the role of women: some room for development.

PMID- 16282121
TI  - The challenge of the other.

PMID- 16282122
TI  - In search of a real "Third Way" in process and outcome.

PMID- 16282123
TI  - Is the middle ground vanishing?

PMID- 16282126
TI  - Accommodation, presbyopia, and the lenticular syneretic response.

PMID- 16282127
TI  - Prospects for developing an effective vaccine against ocular herpes simplex virus
      infection.
AB  - One of the hallmarks of herpes simplex virus (HSV) infection is the establishment
      of a lifelong latent infection accompanied by periods of recurrent disease.
      Primary HSV infections or repeated clinical recurrences do not elicit immune
      responses capable of completely preventing recurrences of endogenous virus. It is
      therefore questionable if vaccination approaches that seek to mimic the immune
      response to natural infection will reduce infection or disease due to an
      exogenous viral challenge. Approaches to the induction of protective responses by
      altering or enhancing both innate and adaptive immunity, using novel vaccines
      specifically tested in models of HSV infections of the eye, such as recombinant
      viral vaccine vectors and DNA vaccines, are detailed in this review.

PMID- 16282129
TI  - Glucocorticoid regulation of endothelial cell tight junction gene expression:
      novel treatments for diabetic retinopathy.
AB  - Loss of blood-retinal barrier (BRB) integrity and vascular permeability
      characterizes diabetic retinopathy, and new therapies to reverse or prevent
      vascular permeability are needed to treat this debilitating disease.
      Glucocorticoids are currently under investigation for use as a local therapeutic
      treatment for diabetic retinopathy. This review examines the changes that occur
      to barrier properties in diabetic retinopathy and the potential to use
      glucocorticoids to restore vascular barrier properties in the retina.
      Glucocorticoids are useful in preserving the integrity of the blood-brain barrier
      in the treatment of brain tumors, and these steroids show similar effects on the
      retinal vasculature suggesting their potential usefulness in treating diabetic
      retinopathy. Recent progress has been made toward the goal of elucidating the
      precise mechanism underlying the protective effects of glucocorticoids on the
      retinal vasculature. Glucocorticoids may act by both suppressing inflammation and
      by directly affecting the endothelial cells by regulating phosphorylation,
      organization, and content of tight junction proteins. Further work will advance
      our understanding of glucocorticoid regulation of barrier properties allowing the
      ultimate goal of developing a specific and safe therapy to treat or prevent loss
      of the blood-neural barrier in a number of diseases, including brain tumors and
      diabetic retinopathy.

PMID- 16282128
TI  - Clinical patterns and characteristics of uveitis in a tertiary center for uveitis
      in China.
AB  - PURPOSE: To address the clinical pattern and characteristics of uveitis in a
      tertiary center for uveitis in China and compare the similarity and difference in
      the distribution of uveitis entities between China and other countries. METHODS:
      A retrospective study was performed on the patients with uveitis referred to the
      Zhongshan Ophthalmic Center from January 1996 to December 2003. The clinical data
      including category, etiology, gender, and the age of the patients at uveitis
      presentation were analyzed and compared with studies published previously from
      other countries. RESULTS: There were 902 male and 850 female patients in our
      series. The mean age of these patients at uveitis presentation was 33.8 +/- 16.5
      years. Anterior uveitis (800, 45.6%) was the most common anatomical entity,
      followed by panuveitis (727, 41.5%), posterior uveitis (119, 6.8%), and
      intermediate uveitis (106, 6.1%). Further classification with the etiology
      criteria revealed 16 entities in anterior uveitis, with idiopathic anterior
      uveitis being the most common entity (473, 27.0%). Twelve entities were
      identified in panuveitis, of which Behcet disease (289, 16.5%) and Vogt-Koyanagi
      Harada (VKH) syndrome (278, 15.9%) were the predominant ones. No specific entity
      was recognized in the intermediate uveitis group. Although a number of specific
      entities were identified in posterior uveitis, toxoplasmosis was noted in only
      two patients in this group. CONCLUSIONS: Idiopathic anterior uveitis, Behcet
      disease, and VKH syndrome are the most common entities of uveitis in China.
      Ocular toxoplasmosis, ocular histoplasmosis, and birdshot retinochoroidopathy are
      less common or absent in China.

PMID- 16282130
TI  - 20:5n-3 but not 22:6n-3 is a preferred substrate for synthesis of n-3 very-long-
      chain fatty acids (C24-C36) in retina.
AB  - The objective of this study was to determine if 20:5n-3 or 22:6n-3 is the primary
      precursor of very-long-chain fatty acids (VLCFAs; C24-C36) synthesized in retina.
      Rats were fed semisynthetic, nutritionally complete diet containing 20% (w/w) fat
      with 3% (w/w) of 22:6n-3. After 6 weeks feeding, the vitreal fluid of each eye
      was injected with [3H]20:5n-3 or [3H]22:6n-3. Rats were then maintained under
      constant light (330 lux) or dark conditions for 48 hr. After 48 hr in vivo
      metabolism, the amount of label present in individual fatty acids was determined
      in major phospholipids in retina. For [3H]22:6n-3, 90% of total incorporation
      remained in 22:6n-3, whereas for [3H]20:5n-3 the label was actively incorporated
      into pentaenoic and hexaenoic VLCFAs up to 34 carbon chain length. 22:5n-3
      derived from [3H]20:5n-3 was among the most highly labeled fatty acids. These
      observations suggest that 22:6n-3 is incorporated directly into retinal
      phospholipids without further metabolism, whereas 20:5n-3 and 22:5n-3 are
      metabolically active precursors for synthesis of VLCFAs.

PMID- 16282131
TI  - FK506 in a biodegradable glycolide-co-clatide-co-caprolactone polymer for
      prolongation of corneal allograft survival.
AB  - PURPOSE: FK506 has been extensively used in preventing immune rejection for human
      organ transplantation. This study aimed to evaluate the effects of a
      biodegradable FK506 drug delivery system (DDS) implanted into anterior chamber
      for the prolongation of corneal allograft survival in high-risk keratoplasty.
      METHODS: Biodegradable glycolide-co-clatide-co-caprolactone polymer (PGLC) was
      used as drug carrier to be incorporated with 0.5 mg of FK506 powder. The drug
      release from the FK506-PGLC DDS was evaluated in vitro and in vivo. The FK506
      PGLC DDS was implanted into the anterior chamber of 12 high-risk keratoplasty
      rabbits. The graft survival time and clinical features of the FK506-PGLC DDS
      group were compared with the untreated, PGLC DDS, cyclosporin A-PGLC DDS, and
      0.5% FK506 drops groups. The histopathological examination was performed to
      evaluate the safety of the FK506-PGLC DDS. RESULTS: The mean graft survival time
      was longest (> 180 days) in the FK506-PGLC DDS group. In vivo, the FK506
      concentration in aqueous humor peaked on day 28 (17.9 +/- 2.3 ng/ml) and kept a
      sustained release for at least 168 days. No adverse reactions were observed in
      the FK506-PGLC DDS group. CONCLUSIONS: Biodegradable FK506-PGLC DDS implanted
      into anterior chamber can effectively prevent immune rejection in high-risk
      keratoplasty model, presenting a promising approach for the prolongation of
      corneal allograft survival.

PMID- 16282132
TI  - Staining and peeling of the internal limiting membrane in the cat eye.
AB  - PURPOSE: To investigate the cat vitreomacular interface using trypan blue (TB)
      and indocyanine green (ICG) and to determine the validity of the cat model in
      terms of staining and peeling of the internal limiting membrane (ILM). METHODS:
      Lensectomy and vitrectomy were performed in four eyes of two cats. The ILM of two
      eyes was stained with TB (0.15%). ILM peeling was performed in one eye. Two eyes
      were stained with ICG (0.5%). One eye was illuminated for 3 min. Light and
      transmission electron microscopy and confocal microscopy were performed. RESULTS:
      Clinically, both dyes stained the cat ILM similar to human ILM. TB staining
      resulted in a normal ultrastructure and antigenity of the retina. ILM peeling was
      associated with intraretinal bleeding. There were fragments of Muller cells
      adherent to the retinal side of the ILM, and Muller cell endfeet were ruptured
      and avulsed. ICG staining of the ILM followed by illumination caused severe inner
      retinal damage. ICG without illumination resulted in focal ILM detachments
      associated with tearing of Muller cell endfeet. CONCLUSIONS: The cat can be used
      as a model to study the effect of TB and ICG on the central area of the cat
      retina, as previous results from clinical and experimental postmortem settings in
      human eyes were confirmed in the current study. Peeling of the ILM as a sheet as
      performed in human macular surgery is not feasible. Differences in the
      ultrastructure of the ILM and a strong adhesion of the ILM to Muller cell endfeet
      may account for this observation.

PMID- 16282133
TI  - Identification and characterization of a Na+-dependent neutral amino acid
      transporter, ASCT1, in rabbit corneal epithelial cell culture and rabbit cornea.
AB  - PURPOSE: The aim of this study was to investigate the presence of a Na+-dependent
      neutral amino acid transporter, ASCT1, in rabbit primary corneal epithelial cell
      culture and rabbit cornea. METHODS: Uptake studies were carried out on rabbit
      primary corneal epithelial culture (rPCEC) cells using 12-well plates. Transport
      studies were conducted with isolated rabbit corneas at 34 degrees C. Uptake and
      transport of L-alanine was determined at various concentrations. Inhibition
      studies were conducted in presence of various L- and D-amino acids, metabolic
      inhibitors like ouabain and sodium azide, and in the absence of sodium to
      delineate the functional characteristics of L-alanine uptake and transport.
      Reverse transcription-polymerase chain reaction (RT-PCR) was performed on total
      RNA harvested from rabbit cornea and rPCEC cells for identification of ASCT1.
      RESULTS: Uptake of L-Ala was found to be saturable with a Km of 0.71 mM and a
      Vmax value of 0.84 micromoles min(-1) mg(-1) protein. Uptake was independent of
      pH and energy but depends on sodium. It was inhibited by serine, threonine,
      cysteine, and glutamine but did not respond to BCH (2-aminobicyclo [2,2,1]
      heptane-2-carboxylic acid) and MeAIB (alpha -methylaminoisobutyric acid).
      Transport of L-Ala across rabbit cornea was also saturable (Km 6.52 mM and Vmax
      1.09 x 10(-2) micromoles min(-1) cm(-2)), energy independent, and subject to
      similar competitive inhibition. Presence of ASCT1 on rPCEC and on rabbit cornea
      was identified by RT-PCR. CONCLUSIONS: L-Alanine, the chosen model substrate, was
      actively transported by Na+-dependent, neutral amino acid exchanger ASCT1, which
      was identified and functionally characterized on rPCEC cells and rabbit cornea.

PMID- 16282134
TI  - Altered retinal neovascularization in TNF receptor-deficient mice.
AB  - PURPOSE: Tumor necrosis factor alpha (TNF-alpha) has been shown to play an
      integral role in inflammation, apoptosis, and angiogenesis. We induced
      retinopathy in tumor necrosis factor receptor-deficient mice (TNFR-) in order to
      examine the role TNF-alpha plays in the pathogenesis of retinopathy of
      prematurity. METHODS: On postnatal day (P) 7, TNFR-knockout mice and their
      congenic controls, B6129JF1 (B6129) mice, were exposed to 75% oxygen for up to 5
      days and then allowed to recover in room air. Retinopathy was qualitatively
      assessed by examining fluorescein (FITC) angiography. Furthermore, retinal
      vascular changes were quantified by immunolabeling retinal vessels in cross
      sections with an anti-type IV collagen antibody. Disease pathology was quantified
      by counting preretinal neovascular nuclei. TUNEL analysis was performed to
      determine if TNFR-mice exhibited a reduced number of apoptotic cells after oxygen
      induced retinopathy. RESULTS: FITC-perfused retinas qualitatively demonstrated
      similar degrees of vascular development and vaso-obliteration on P12 in the room
      air and hyperoxia-exposed TNFR- and B6129 mice. On P17, the hyperoxia-exposed
      TNFR- and B6129 mice qualitatively appeared to develop a similar degree of
      retinal neovascularization. However, FITC-perfused retinal flat mounts on P21
      suggested that the hyperoxia-exposed TNFR-mice had a prolonged neovascular
      response compared to the hyperoxia-exposed B6129 mice. Type IV collagen staining
      revealed delayed development of the deep intraretinal vessels in the TNFR-room
      control mice and hyperoxia-exposed TNFR-mice, as compared with B6129 controls. On
      P17, the average number of preretinal nuclei was similar between the hyperoxia
      exposed TNFR-mice and B6129 mice. However, on P21, the neovascularization in the
      B6129 mice had regressed (3.9 +/- 0.57, preretinal nuclei), whereas
      neovascularization in the TNFR-mice remained prominent (25.6 +/- 6.3, preretinal
      nuclei). On P21, the B6129 mice exhibited increased apoptosis in preretinal
      vascular tufts as compared with TNFR- mice. CONCLUSIONS: TNFR- mice had both an
      altered development of the intraretinal vessels and altered angiogenic response
      after hyperoxia. Therefore, absence of the TNF-alpha pathway appears to disrupt
      the local microenvironment promoting angiogenesis in the deep retinal vascular
      network, as well as altering tuft regression by modifying endothelial cell
      apoptosis.

PMID- 16282135
TI  - Dehydrated form of plasmid expressing basic fibroblast growth factor
      polyethylenimine complex is a novel and accurate method for gene transfer to the
      cornea.
AB  - PURPOSE: We describe a novel vector system of nonviral gene transfer into the
      cornea using a dehydrated form of a plasmid expressing basic fibroblast growth
      factor-polyethylenimine (p-bFGF-PEI) complex to induce angiogenesis. METHODS:
      Corneal neovascularization was evaluated in 48 eyes of Sprague-Dawley rats after
      implantation of a dehydrated form of PEI containing 1 microg green fluorescent
      protein (p-GFP-PEI; control group), or 10 microg, 1 microg, or 0.1 microg of p
      bFGF-PEI introduced by spin vacuum at ambient temperature. Neovascularization was
      observed and quantified from day 1 to day 45. Eighteen kDa bFGF protein
      expression was analyzed by Western blot and immunohistochemistry. RESULTS: Limbal
      vessels began to sprout on day 3 in the p-bFGF-PEI groups. The dehydrated form of
      the p-bFGF-PEI complex induced dose-dependent corneal neovascularization, which
      reached a maximum on days 24-30 in the 10 microg bFGF group, days 18-24 in the 1
      microg bFGF group, and days 15-21 in 0.1 microg bFGF group, and then regressed
      progressively. No neovascularization was observed in the GFP group. CONCLUSIONS:
      The dehydrated form of the p-bFGF-PEI complex is a novel and precise method for
      controlling the dose, localizing the reagents, and avoiding loss of liquid form
      during transfection into corneal tissue.

PMID- 16282136
TI  - Intravitreal administration of erythropoietin and preservation of retinal
      ganglion cells in an experimental rat model of glaucoma.
AB  - PURPOSE: The aim of this pilot study was to evaluate the potential
      neuroprotective effect of an intravitreal injection of erythropoietin (EPO) on
      retinal ganglion cell (RGC) preservation in an episcleral vessel cautery-induced
      rat model of glaucoma. METHODS: The animals were randomly assigned into an
      unoperated control group (n = 11) and three experimental groups: episcleral
      vessel cautery only (EVC: n = 4), episcleral vessel cautery with intravitreal
      normal saline injection (EVC-NS; n = 5), and episcleral vessel cautery with
      intravitreal EPO treatment (EVC-EPO; n = 9). The intravitreal injections were
      limited to 5 mul containing either normal saline alone or 200 ng of EPO in normal
      saline administered immediately after the cautery procedure. RGCs were labeled
      retrogradely by FluoroGold neuron tracer 5 to 7 days prior to the collection of
      eyes at day 21 and counted in whole flat-mounted retinas with fluorescence
      microscopy. RESULTS: Compared to the RGC counts in retinal specimens from
      unoperated control rats (12,619 +/- 310), the corresponding RGC counts were
      significantly decreased in both the EVC (9116 +/- 273; p < 0.005) and EVC-NS
      (9489 +/- 293; p < 0.005) groups but not significantly decreased in the EVC-EPO
      (11,212 +/- 414; p = 0.051) treated retinas. CONCLUSIONS: A single intravitreal
      200 ng dose of EPO appears to have a protective effect on RGC viability in an in
      vivo rat model of glaucoma. Further experimental studies are needed to confirm
      these preliminary results and to optimize the appropriate dose and frequency of
      EPO delivery in animal models of glaucoma.

PMID- 16282139
TI  - Rawls' theory of justice: a naturalistic evaluation(1).
AB  - This article critically evaluates John Rawls' theory of justice from a
      naturalistic perspective. The naturalistic approach is increasingly advocated in
      contemporary epistemology, philosophy of science, and philosophy of logic.
      Recently this approach has also become more influential in the study of ethics.
      Based on an experimental study on social justice conducted in Hong Kong, Beijing,
      and Taipei, this article argues that although Rawls' theory of justice has a
      naturalistic flavor, it has difficulty in standing up against the scrutiny of
      empirical tests if he commits himself to a fully fledged naturalistic approach.

PMID- 16282140
TI  - Empirical ethics, context-sensitivity, and contextualism.
AB  - In medical ethics, business ethics, and some branches of political philosophy
      (multi-culturalism, issues of just allocation, and equitable distribution) the
      literature increasingly combines insights from ethics and the social sciences.
      Some authors in medical ethics even speak of a new phase in the history of
      ethics, hailing "empirical ethics" as a logical next step in the development of
      practical ethics after the turn to "applied ethics." The name empirical ethics is
      ill-chosen because of its associations with "descriptive ethics." Unlike
      descriptive ethics, however, empirical ethics aims to be both descriptive and
      normative. The first question on which I focus is what kind of empirical research
      is used by empirical ethics and for which purposes. I argue that the ultimate aim
      of all empirical ethics is to improve the context-sensitivity of ethics. The
      second question is whether empirical ethics is essentially connected with
      specific positions in meta-ethics. I show that in some kinds of meta-ethical
      theories, which I categorize as broad contextualist theories, there is an
      intrinsic need for connecting normative ethics with empirical social research.
      But context-sensitivity is a goal that can be aimed for from any meta-ethical
      position.

PMID- 16282141
TI  - Harming by conceiving: a review of misconceptions and a new analysis.
AB  - An objection often is raised against the use of reproductive technology to create
      "nontraditional families," as in ovum donation for postmenopausal women or
      postmortem artificial insemination. The objection states that conceiving children
      in such circumstances is harmful to them because of adverse features of these
      nontraditional families. A similar objection is raised when parents, through
      negligence or willful disregard of risks, create children with serious genetic
      diseases or other developmental handicaps. It is claimed that such reproduction
      harms the children who are created. In reply to this Harm to the Child Argument,
      it has been pointed out that the procreative acts that supposedly harm the child
      are the very acts that create the child. This reply has been developed into an
      argument that, in most of the types of cases under consideration, creating the
      child does not harm her. This reply, the No Harm Argument, has been stated in
      three main ways, and it is one of the most misunderstood arguments in bioethics.
      This paper examines the main rebuttals that have been made to the No Harm
      Argument and argues that none of them is successful.

PMID- 16282142
TI  - Euthanasia and physicians' moral duties.
AB  - Opponents of euthanasia sometimes argue that it is incompatible with the purpose
      of medicine, since physicians have an unconditional duty never to intentionally
      cause death. But it is not clear how such a duty could ever actually be
      unconditional, if due consideration is given to the moral weight of
      countervailing duties equally fundamental to medicine. Whether physicians' moral
      duties are understood as correlative with patients' moral rights or construed
      noncorrelatively, a doctor's obligation to abstain from intentional killing
      cannot be more than a defeasible duty.

PMID- 16282143
TI  - Luck, risk, and blame.
AB  - In this article, I defend luck at the expense of risk. Or, more precisely, I try
      to make a distinction that gives both concepts fair treatment. I start by making
      it clear that luck stands in opposition to control and not to causation. Both
      luck and risk are related to causal uncertainty. But it is warranted to talk
      about risk only when the uncertainty involved is brought under control, as it is
      in some familiar forms of fair gambling such as dicing and roulette. Life is
      however not a fair gamble. We rarely have the kind of control over the
      preconditions of life that we have over the preconditions of say dicing. Luck
      therefore has profound influence on our lives and our health. This means that the
      standard conception of responsibility-that is, that we stand responsible only for
      consequences that we control - breaks down far more often than what is usually
      acknowledged. I therefore end the article by arguing that the standard conception
      of responsibility ought to be supplemented with a different conception that I
      have called "responsibility because of social involvement."

PMID- 16282146
TI  - Toxoplasmosis.
AB  - Toxoplasmosis is the most common cause of posterior uveitis in immunocompetent
      subjects. The infection can be congenital or acquired. Ocular symptoms are
      variable according to the age of the subject. For instance, young children
      present with reduced visual acuity, strabismus, nystagmus, and leucocoria, while
      teenagers and adults complain of decreased vision, floaters, photophobia, pain,
      and hyperemia. Toxoplasmic retinochoroiditis typically affects the posterior
      pole, and the lesions can be solitary, multiple or satellite to a pigmented
      retinal scar. Active lesions present as grey-white focus of retinal necrosis with
      adjacent choroiditis, vasculitis, hemorrhage and vitreitis. Cicatrization occurs
      from the periphery towards the center, with variable pigmentary hyperplasia.
      Anterior uveitis is a common finding, with mutton-fat keratic precipitates,
      fibrine, cells and flare, iris nodules and posterior synechiae. Atypical
      presentations include punctate outer retinitis, neuroretinitis, papillitis,
      pseudo-multiple retinochoroiditis, intraocular inflammation without
      retinochoroiditis, unilateral pigmentary retinopathy, Fuchs'-like anterior
      uveitis, scleritis and multifocal or diffuse necrotizing retinitis. The
      laboratory diagnosis of toxoplasmosis is based on detection of antibodies and T.
      gondii DNA using polymerase chain reaction (PCR). Toxoplasmosis therapy includes
      specific medication and corticosteroids. There are several regimens, with
      different drug combinations. Medications include pirimetamine, sulfadiazine,
      clindamycin, trimethoprime-sulphamethoxazol, spiramycin, azithromycin,
      atovaquone, tetracycline and minocycline. The prognosis of ocular toxoplasmosis
      is usually good in immunocompetent individuals, as long as the central macula is
      not directly involved.

PMID- 16282147
TI  - Fuchs' heterochromic cyclitis.
AB  - Fuchs' heterochromic cyclitis (FHC) is a chronic anterior segment inflammatory
      syndrome that accounts for 2 to 3% of all uveitis cases. The etiology is unknown,
      but Herpes simplex, ocular toxoplasmosis and rubella infection have been
      implicated in the pathogenesis of the disease. It occurs more commonly in the
      third and fourth decades of life with an equal gender distribution. Patients are
      usually asymptomatic but may present with floaters and blurry vision. There is a
      mild but persistent anterior chamber reaction with diffuse and characteristic
      white stellate keratic precipitates. Iris and trabecular meshwork show abnormal
      vessels that may sometimes lead to a hyphema. Synechia formation is uncommon.
      Heterochromia is considered an important feature and accounts for the name, but
      it is variable depending on the intensity of the anterior stromal atrophy,
      initial iris color and amount of pigment in the iris pigmented epithelium.
      Progression of the disease is associated with cataract formation and glaucoma.
      Anti-inflammatory treatment is not indicated for the low-grade anterior chamber
      reaction seen in Fuchs' patients. Occasionally, a short course of corticosteroids
      is indicated if a symptomatic exacerbation occurs. The long-term prognosis is
      good, and patients usually maintain a visual acuity of 20/40 or better.

PMID- 16282148
TI  - Intermediate uveitis.
AB  - Intermediate uveitis is an intraocular inflammation involving the anterior
      vitreous, peripheral retina and pars plana. It usually affects patients from 5 to
      30 years old, without gender or racial preferences. The etiology is unknown but
      there are several associated diseases: multiple sclerosis, idiopathic optic
      neuritis, autoimmune corneal endotheliopathy, sarcoidosis, thyroid diseases and
      inflammatory bowel diseases. Symptoms are blurry vision, floaters and distortion
      of central vision. The syndrome is bilateral in 80% of the patients and chronic
      with periods of exacerbation and remission. Clinical presentation includes: mild
      to moderate anterior chamber inflammation, thin keratic precipitates in the
      inferior portion of the cornea, autoimmune endotheliopathy, vitreitis, vasculitis
      in the peripheral retina, intravitreal "snowballs," retinal "snowbanking," optic
      neuritis and cystoid macular edema. Cataract and glaucoma are frequent
      complications. Treatment of intermediate uveitis is based on periocular and oral
      corticosteroids. Cryotherapy or laser photocoagulation of the peripheral retina
      are options in patients with snowbanking when there is an insufficient response
      to periocular or systemic corticosteroids. Imunosuppression may also be used when
      other therapies fail, and Cyclosporin A is the first drug of choice. Pars plana
      vitrectomy is indicated in patients with chronic significant inflammation, non
      responsive cystoid macular edema, non-clearing vitreous hemorrhage, tractional
      retinal detachment and epiretinal membranes. The long-term prognosis of
      intermediate uveitis is usually good, particularly with strict control of
      inflammation and with proper management of complications. Patients can often
      maintain a vision of 20/50 or better.

PMID- 16282149
TI  - Acute retinal necrosis.
AB  - Acute retinal necrosis (ARN) is an uncommon intraocular inflammatory syndrome
      characterized by severe and diffuse uveitis, retinal vasculitis, and retinal
      necrosis. It is typically described to occur in immunocompetent patients, but can
      also be found in immunocompromised subjects. Varicella-zoster virus (VZV), herpes
      simplex virus (HSV 1 and 2), cytomegalovirus (CMV), and Epstein-Barr virus (EBV)
      have been implicated in the etiology of ARN. The characteristic features of the
      disease include iridocyclitis, vitritis, retinal vasculitis, and retinal
      necrosis. Bilateral involvement occurs in two-thirds of the patients, frequently
      in the first six weeks, but sometimes months to years later. Retinal detachment
      occurs in 75% of the cases. The diagnosis of ARN is usually based in clinical
      features. The use of polymerase chain reaction (PCR) in aqueous humor samples is
      useful to identify the etiology of the disease. The treatment of ARN includes
      intravenous acyclovir, corticosteroids and aspirin. To prevent fellow eye
      involvement, intravenous acyclovir is followed by oral acyclovir for 14 weeks.
      Alternatives to acyclovir include ganciclovir, foscarnet, famcyclovir, brivudine,
      and valgancyclovir.

PMID- 16282150
TI  - Ocular manifestations and treatment of syphilis.
AB  - Syphilis is a sexually transmitted, chronic, systemic infection caused by the
      spirochete Treponema pallidum. If left untreated, the disease progresses through
      four stages, with the potential to cause significant morbidity to any major organ
      of the body. Frequent syphilitic ocular manifestations, which can occur at any
      stage of the disease, include interstitial keratitis, anterior, intermediate, and
      posterior uveitis, chorioretinitis, retinitis, retinal vasculitis and cranial
      nerve and optic neuropathies. Diagnosis is centered around a high level of
      clinical suspicion and includes treponemal specific and non-treponemal serologic
      tests. All patients with newly diagnosed syphilis should be tested for co
      infection with human immunodeficiency virus, as the risk factors are similar for
      both diseases. Additionally, all patients with ocular syphilis should be tested
      for neurosyphilis. The preferred treatment for all stages of syphilis remains
      parenteral penicillin G. With proper diagnosis and prompt antibiotic treatment,
      the majority of cases of syphilis can result in a cure.

PMID- 16282151
TI  - Tuberculosis.
AB  - Tuberculosis is caused by Mycobacterium tuberculosis, transmitted primarily by
      inhalation of aerosolized droplets containing the organisms. There is an
      infection of the respiratory tract and the tubercle bacilli spread via lymphatic
      system and bloodstream to many different organs. Generally, the pulmonary
      tuberculosis infections are asymptomatic and a positive skin test result is the
      only indication of it. Approximately 10% of infected individuals develop active
      disease. Immunosuppression caused by systemic diseases or medication increases
      the risk of developing tuberculosis. In addition to the pulmonary tract,
      tuberculosis may affect many organs and systems, including lymph nodes, larynge,
      middle ear, genitourinary tract, musculoskeletal system, central nervous system,
      gastrointestinal tract, pericardium, and skin. Ocular involvement is an uncommon
      event in tuberculous infection, and there are several presentations involving the
      iris, ciliary body, choroid, retina and optic nerve. The diagnosis is based in
      the detection of mycobacteria in fluids and tissues. If there is no available
      material for analysis, a presumptive diagnosis is made and therapeutic test
      initiated. The therapy is based in anti-tuberculous drugs and corticosteroids.
      The standard treatment protocol in Brazil includes isoniazid, rifampim, and
      pyrazinamid for two months, followed by isoniazid and rifampin for four months
      for susceptible organisms. Alternative regimens are necessary in the presence of
      drug resistance.

PMID- 16282152
TI  - Sarcoidosis.
AB  - Sarcoidosis is a multisystem granulomatous disease with an unknown etiology,
      characterized by the presence of noncaseating granulomas in involved organs. It
      has a worldwide prevalence, but variable incidence among different geographical
      regions. The disease affects adults between 20 and 40 years of age, and it is
      slightly more common in women than men. Sarcoidosis is 3 to 4 times more
      prevalent in US blacks than whites. It usually presents with bilateral hilar
      adenopathy, pulmonary infiltrates and skin or eye involvement. The eye or adnexa
      are affected in 25 to 80% of the sarcoidosis patients. The disease can involve
      the orbit, lacrimal gland, anterior and posterior segments of the eye. Typical
      sarcoid uveitis presents with bilateral mutton-fat keratic precipitates, cells,
      flare, iris nodules, anterior and posterior synechia, and increased ocular
      pressure. Posterior involvement includes vitreitis, vasculitis, choroidal
      lesions, and optic neuropathy. Long term complications are common, and cystoid
      macular edema is the most important and sight-threatening consequence. Laboratory
      tests for the diagnosis of sarcoidosis include chest radiography or CT scan,
      bronchoscopy with bronchoalveolar lavage, angiotensin converting enzyme (ACE),
      Lysozyme, serum and urinary calcium, gallium scintigraphy, and biopsy. The only
      confirmatory test is biopsy showing classic noncaseating granulomas. Oral
      corticosteroids are the mainstay of treatment of sarcoidosis. Systemic cytotoxic
      agents like methrotrexate, azathioprine, and chlorambucil may be used in
      refractory cases. The visual prognosis of sarcoidosis is usually good.

PMID- 16282153
TI  - Vogt-Koyanagi-Harada disease.
AB  - Vogt-Koyanagi-Harada disease (VKH) is a multisystem autoimmune disorder
      principally affecting pigmented tissues in the ocular, auditory, integumentary
      and central nervous systems. Patients are typically 20 to 50 years old and have
      no history of either surgical or accidental ocular trauma. Pigmented races are
      more commonly affected. Depending on revised diagnostic criteria, the disease is
      classified as complete, incomplete or probable based on the presence of
      extraocular findings (neurological, auditory and integumentary). The clinical
      course of VKH is divided into four phases: prodromal (mimics a viral infection),
      uveitic (bilateral diffuse uveitis with papillitis and exudative retinal
      detachment), convalescent (tissue depigmentation), and chronic recurrent
      (recurrent uveitis and ocular complications). The pathogenesis of VKH is thought
      to be related to an aberrant T cell-mediated immune response directed against
      self-antigens found on melanocytes. VKH has been linked to human leukocyte
      antigen DR4 (HLA-DR4) and HLA-Dw53, with strongest associated risk for HLA
      DRB1*0405 haplotype. The diagnosis of VKH is clinical, and differential includes
      sympathetic ophthalmia, sarcoidosis, primary intraocular B-cell lymphoma,
      posterior scleritis, and uveal effusion syndrome. Treatment is typically
      initiated with high-dose oral corticosteroids, but other immunomondulatory agents
      (most oftentimes cyclosporine) may be needed for non-responsive patients or when
      corticosteroid side-effects are not tolerated. Visual prognosis is generally good
      with prompt diagnosis and aggressive immunomodulatory treatment.

PMID- 16282154
TI  - Sympathetic ophthalmia.
AB  - Sympathetic ophthalmia is a rare, bilateral granulomatous uveitis that occurs
      after either surgical or accidental trauma to one eye. The ocular inflammation in
      the fellow eye becomes apparent usually within 3 months after injury. Clinical
      presentation is an insidious or acute anterior uveitis with mutton-fat keratic
      precipitates. The posterior segment manifests moderate to severe vitritis,
      usually accompanied by multiple yellowish-white choroidal lesions. Evidence
      suggests that sympathetic ophthalmia represents an autoimmune inflammatory
      response against choroidal melanocytes mediated by T cells. Diagnosis is based on
      clinical findings and a history of previous ocular trauma or surgery. Other
      causes of granulomatous uveitis, such as Vogt-Koyanagi-Harada disease,
      sarcoidosis, tuberculosis, and syphilis should be considered. Treatment of
      sympathetic ophthalmia consists of systemic anti-inflammatory agents with high
      dose oral corticosteroid as the drug of choice. However, if the inflammation
      cannot be controlled, cyclosporine is then used. Other immunosuppressive agents,
      such as chlorambucil, cyclophosphamide or azathioprine, may be necessary for the
      control of inflammation. The role of enucleation after the diagnosis of
      sympathetic ophthalmia remains controversial. Visual prognosis is reasonably good
      with prompt wound repair and appropriate immunomodulatory therapy.

PMID- 16282156
TI  - Stability of ferruginous bodies in human lung tissue following death, embalmment,
      and burial.
AB  - The identification of asbestos bodies in tissue sections is an indicator of past
      exposure to longer asbestos fibers. These structures are formed in lung tissue as
      a consequence of interactions with pulmonary macrophages resulting in the
      deposition of a ferroprotein (ferruginous) coating on the fiber. While the
      process of ferruginous body formation is known to take months in animal tissue,
      there is no published information on the stability of ferruginous bodies in
      tissue following death. The material assessed in the present study was obtained
      from lung material collected from an exhumed body approximately 8(1/2) mo after
      death, embalmment, and burial. Tissue sections were reviewed for the presence of
      asbestos bodies. Additional pieces of lung tissue were digested, with the
      digestate being evaluated by light microscopy for ferruginous bodies and by
      electron microscopy for uncoated asbestos fibers and core analysis of asbestos
      bodies. Classical ferruginous (asbestos) bodies were found in abundance in the
      tissue sections including in areas with fibrosis. The levels of uncoated asbestos
      fibers and classical appearing ferruginous bodies (asbestos bodies) were
      consistent with occupational levels of tissue burden. The data from this study
      indicate that ferruginous bodies remain morphologically stable within the tissue
      for months following death, embalmment, and burial. Thus the lung tissue from
      this exhumed individual was usable not only to pathologically confirm asbestosis
      but also to provide quantitative data of occupational exposure to asbestos.

PMID- 16282155
TI  - Behcet's disease.
AB  - Behcet's disease is a chronic, relapsing vasculitis that can affect most organ
      systems. The prevalence varies geographically, and the disease is more common in
      countries along the ancient Silk Road, including Italy, Turkey, Israel, Saudi
      Arabia, Iran, China, Korea and Japan. Behcet's is more common in men than in
      women, and typically affects young adults. The classic finding in Behcet's
      patients is the presence of recurrent mucocutaneous ulcers, and oral aphthous
      ulcerations are usually the initial symptom. Other manifestations include genital
      ulcers, skin lesions, vascular, neurological, articular, and ocular disease. The
      disease can affect the anterior and/or posterior segments of the eye, and the
      main manifestations include iridocyclitis, hypopyon, mild to moderate vitreitis,
      retinal vasculitis and occlusion, optic disc hyperemia, and macular edema. There
      is no pathognomonic laboratory test in Behcet's disease, and the diagnosis is
      based in systemic and ocular clinical findings. Treatment of ocular Behcet is
      based in corticosteroids and immunosuppressive agents, to suppress acute
      inflammation and reduce its recurrence frequency. Ocular lesions may improve with
      immunosuppressive therapy, but usually are not fully reversible, and generally
      progress over time. The prognosis of anterior uveitis is usually good, but
      patients with posterior lesions tend to have some degree of visual loss, even
      with adequate treatment.

PMID- 16282157
TI  - A case of carbon monoxide poisoning with thrombus in the heart: a case report.
AB  - Carbon monoxide is a nonirritant, odorless, colorless gas, and is lighter than
      air. It is an end product of the incomplete combustion of hydrocarbons. Its
      effects are most prominent in organs sensitive to oxygen deprivation, such as the
      heart, brain, and kidney. Carbon monoxide poisoning becomes more abundant in
      winter and at cold places. In Turkey, every year we see several deaths due to
      poisonous gas leaks from coal or wood stoves. Deaths particularly due to hypoxia
      related central nervous system damage and ventricular dysrhythmias are observed.
      On the other hand, an association between thromboembolic accidents and carbon
      monoxide poisoning has been shown in literature. Thromboembolic accidents in the
      mesenteric, central nervous system, and extremities are reported. However, no
      atrial thrombus has been mentioned. In this study, a case of an atrial thrombus
      associated with carbon monoxide poisoning following a diagnosis of carbon
      monoxide poisoning and treatment in the emergency room is reported and the
      literature is revisited.

PMID- 16282158
TI  - Fine particulate air pollution and total mortality among elderly Californians,
      1973-2002.
AB  - Fine particulate air pollution has been associated with increases in long-term
      mortality in selected cohort studies, and this association has been influential
      in the establishment of air quality regulations for fine particles (PM(2.5)).
      However, this epidemiologic evidence has been questioned because of
      methodological issues, conflicting findings, and lack of an accepted causal
      mechanism. To further evaluate this association, the long-term relation between
      fine particulate air pollution and total mortality was examined in a cohort of
      49, 975 elderly Californians, with a mean age of 65 yr as of 1973. These
      subjects, who resided in 25 California counties, were enrolled in 1959,
      recontacted in 1972, and followed from 1973 through 2002; 39, 846 deaths were
      identified. Proportional hazards regression models were used to determine their
      relative risk of death (RR) and 95% confidence interval (CI) during 1973-2002 by
      county of residence. The models adjusted for age, sex, cigarette smoking, race,
      education, marital status, body mass index, occupational exposure, exercise, and
      a dietary factor. For the 35, 789 subjects residing in 11 of these counties,
      county-wide exposure to fine particles was estimated from outdoor ambient
      concentrations measured during 1979-1983 and RRs were calculated as a function of
      these PM(2.5) levels (mean of 23.4 microg/m(3)). For the initial period, 1973
      1982, a small positive risk was found: RR was 1.04 (1.01-1.07) for a 10
      microg/m(3) increase in PM(2.5). For the subsequent period, 1983-2002, this risk
      was no longer present: RR was 1.00 (0.98-1.02). For the entire follow-up period,
      RR was 1.01 (0.99-1.03). The RRs varied somewhat among major subgroups defined by
      sex, age, education level, smoking status, and health status. None of the
      subgroups that had significantly elevated RRs during 1973-1982 had significantly
      elevated RRs during 1983-2002. The RRs showed no substantial variation by county
      of residence during any of the three follow-up periods. Subjects in the two
      counties with the highest PM(2.5) levels (mean of 36.1 microg/m(3)) had no
      greater risk of death than those in the two counties with the lowest PM(2.5)
      levels (mean of 13.1 microg/m(3)). These epidemiologic results do not support a
      current relationship between fine particulate pollution and total mortality in
      elderly Californians, but they do not rule out a small effect, particularly
      before 1983.

PMID- 16282159
TI  - Effects of Asian dust storm events on daily admissions for asthma in Taipei,
      Taiwan.
AB  - In spring, windblown dust storms originating in the deserts of Mongolia and China
      make their way to Taipei city. These occurrences are known as Asian dust storm
      (ADS) events. The objective of this study was to assess the possible associations
      of ADS on the hospital asthma admissions of residents in Taipei, Taiwan, during
      the period 1996-2001. We identified 54 dust storm episodes, which were classified
      as index days. Daily asthma admissions on the index days were compared with
      admissions on the comparison days. We selected two comparison days for each index
      day, 7 days before the index days and 7 days after the index days. The effects of
      dust storms on asthma admissions were prominent 2 days after the event (8%).
      However, the association was not statistically significant. There may not have
      been enough power to detect associations resulting from the inadequate sample
      size of asthma admissions on ADS events days. However, it seems worthwhile to pay
      more attention to the ADS events and health in the future.

PMID- 16282160
TI  - Inertial particle deposition in a monkey nasal mold compared with that in human
      nasal replicas.
AB  - Information on nasal particle deposition is used in risk assessments for exposure
      to airborne particulate pollutants and for optimizing the delivery of therapeutic
      aerosols. Monkeys are commonly used to assess the therapeutic potential of
      inhaled substances and to a lesser extent the toxicity of inhaled xenobiotics.
      Yet no reliable measurements of the deposition efficiency of monkey nasal airways
      for particles >1 microm have been reported to date. The goals of this study were
      to measure the deposition efficiency (>1 microm) of a replica of monkey nasal
      airways and to investigate potential differences in nasal deposition between
      humans and monkeys by comparing results with similar measurements recently
      reported for human nasal replicas. The monkey nasal replica was an acrylic mold
      made from a postmortem cast of the nasal airways of a 12-kg, male rhesus monkey.
      Particle deposition in the monkey nasal mold was measured for monodisperse
      aerosols between 1 and 10 microm and constant inspiratory flow rates between 2
      and 7 lpm. Total deposition efficiency increased from nearly 0 to 100% with
      increasing particle inertia and was uniquely determined by values of an inertial
      impaction parameter. The deposition efficiencies of the monkey replica agreed
      well with those of human nasal replicas when compared according to equivalent
      Stokes numbers based on minimum cross-sectional area. Results from this study
      could improve monkey-to-human extrapolation models and interpretations of data
      from particle toxicity and therapeutic aerosol studies using monkeys.

PMID- 16282161
TI  - Particle inhalability at low wind speeds.
AB  - Accurate quantification of the dose delivered by aerosol exposures is essential
      for estimating the risk of potential adverse health effects. The fraction of
      airborne particles that can enter the nose or mouth during inhalation is referred
      to as the inspirable particulate mass fraction. This inhalable fraction is
      equivalent to delivered dose for particles greater than approximately 25 microm
      (aerodynamic particle diameter, d(ae)), which deposit completely and almost
      exclusively in the extrathoracic airways. Particle inhalability at high wind
      speeds (1-9 m/s) has been well characterized. However, there is a paucity of data
      describing the inhalability of particles at low wind speeds (< or =0.3 m/s),
      which are typical of indoor environments. High-wind-speed criteria poorly
      describe inhalability at low wind speeds. Based on the aspiration efficiencies of
      blunt and sharp-edged inlets, a function was developed for oral inhalability,
      P(I(O)), of particles at low wind speeds. This function predicts a slow decline
      in P(I(O)) from 0.95 at d(ae)= 8 microm, to 0.5 at d(ae) = 74 microm, and 0.1 at
      d(ae)= 175 microm. Data available from the literature for inhalability at
      relatively low wind speeds during oral breathing are well described by this
      logistic function (r(2)= 0.69).

PMID- 16282162
TI  - International Workshop on the Design and Analysis of Experimental Studies using
      PM Concentrator Technologies, Boston, May 5, 2004.
AB  - A workshop that brought together representatives of most of the laboratories that
      have conducted animal and/or human inhalation exposure studies with concentrated
      ambient air particles (CAPs) was convened by the Health Effects Institute in
      Boston on May 5, 2004. Participants agreed that CAPs researchers need to make
      serious efforts to harmonize their experimental and analytical protocols to
      permit the sharing of lessons learned, questions raised, and opportunities for
      more definitive studies. Standardized outcome measures based on spirometry and
      response markers in lung bronchoalveolar lavage (BAL) cells and fluids exist,
      including the appropriate times after exposure to collect samples and
      measurements. However, for the emerging focus on cardiac system responses, there
      are many different electrocardiographic (ECG) endpoints being examined, and
      little standardization on markers that are most informative about adverse
      effects; on when the measurements need to be made; and on how to make comparable
      measurements. The workshop focused on two aspects of dealing with these
      complexities: sorting out influential particulate matter (PM) components
      responsible for observed effects, and searching for time-varying responses in
      continuous outcome data. The need for more complete analyses of PM samples from
      the CAPs studies was also emphasized, as was obtaining a consistent set of
      parameters characterizing exposure atmospheres and the ambient PM from which the
      CAPs are sampled. CAPs studies have already had a significant impact within the
      air pollution health effects community, especially in regard to cardiovascular
      system effects, and a follow-up meeting with a greater focus on means to
      harmonize data collection and analysis is needed.

PMID- 16282163
TI  - Health effects of subchronic exposure to diesel-water emulsion emission.
AB  - The U.S. Environmental Protection Agency (EPA) National Ambient Air Quality
      Standards for ozone and particulate matter are requiring urban nonattainment
      areas to implement pollution-reduction strategies for anthropogenic source
      emissions. A type of fuel shown to decrease combustion emissions components
      versus traditional diesel fuels is the diesel-water emulsion. The Lubrizol
      Corporation in conjunction with Lovelace Respiratory Research Institute and
      several subcontracting laboratories recently conducted a rodent health assessment
      of inhaled combustion emissions of PuriNO(x) diesel fuel emulsion. Combustion
      emissions from either of two 2001 model Cummins 5.9-L ISB engines were diluted
      with charcoal-filtered air to exposure concentrations of 100, 200, and 400 microg
      total particulate matter/m(3). The engines were operated on a continuously
      repeating, heavy-duty certification cycle (U.S. Code of Federal Regulations,
      Title 40, Chapter I) using Rotella-T 15W-40 engine oil. Nitrogen oxide and
      particulate matter were reduced when engines were operated on PuriNO(x) versus
      California Air Resources Board diesel fuel under these conditions. Male and
      female F344 rats were housed in Hazleton H2000 exposure chambers and exposed to
      exhaust atmospheres 6 h/day, 5 days/wk for the first 11 wk and 7 days/wk
      threafter. Exposures ranged from 58 to 70 days, depending on the treatment group.
      Indicators of general toxicity (body weight, organ weight, clinical pathology,
      and histopathology), neurotoxicity (glial fibrillary acidic protein assay),
      genotoxicity (Ames assay, micronucleus, sister chromatid exchange), and
      reproduction and development were measured. Overall, effects observed were mild.
      Emulsion combustion emissions were not associated with neurotoxicity,
      reproductive/developmental toxicity, or in vivo genotoxicity. Small decreases in
      serum cholesterol and small increases in platelet values in some groups of
      exposed animals were observed. Particulate matter accumulation within alveolar
      macrophages was evident in all exposure groups. These findings are consistent
      with normal physiological responses to particle inhalation. Other statistically
      significant effects were present in some measured parameters of other exposed
      groups but were not clearly attributed to emissions exposure. Positive mutagenic
      responses in several strains of Salmonella typhimurium were observed subsequent
      to treatment with emulsion emissions subfractions. Based on the cholesterol and
      platelet results, it can be concluded that the 100 microg/m(3) exposure level was
      the no-observed-effect level. In general, biological findings in diesel emulsion
      emission-exposed animals and bacteria were consistent with exposure to petroleum
      diesel exhaust in the F344 rat and Ames assays.

PMID- 16282164
TI  - Air pollution particulate SRM 1648 causes oxidative stress in RAW 264.7
      macrophages leading to production of prostaglandin E2, a potential Th2 mediator.
AB  - Particulates in air pollution have been strongly associated with asthma symptoms.
      These particulates are a conglomeration of many components, including metals,
      polyaromatic hydrocarbons, and lipopolysaccharide, that may cause oxidative
      stress upon uptake by alveolar macrophages. The objective of this study was to
      assess whether uptake of a model air particulate (SRM 1648) causes oxidative
      stress in macrophages resulting in the production of the eicosanoid mediator
      prostaglandin E(2) (PGE(2)) that might exacerbate asthma. SRM 1648 suspended in
      phosphate-buffered saline (PBS) was introduced into wells with plated RAW 264.7
      monocyte/macrophages. Following incubation of SRM 1648 with RAW 264.7
      macrophages, prostaglandin E(2) was measured by enzyme immunosorbent assay (EIA),
      and oxidative stress was assessed by the levels of intracellular reduced
      glutathione (GSH) as well as by the oxidation of dihydrodichlorofluorescein
      (H(2)DCFDA) to the fluorescent dichlorofluoresecein (DCF). The results indicated
      that SRM 1648 caused oxidative stress in RAW 264.7 macrophages, as shown by a
      compensatory increase in GSH levels in comparison to the controls of titanium
      dioxide and media alone. Prostaglandin E(2) levels significantly increased at the
      3-, 6-, and 12-h time points. Introduction of GSH ester to buffer against
      oxidative stress was able to block the elevation of PGE(2). The data show that
      SRM 1648 causes oxidative stress in RAW 264.7 macrophages resulting in formation
      of the potential Th2 mediator prostaglandin E(2).

PMID- 16282165
TI  - Characterization of fine particles from machining in automotive plants.
AB  - Sampling of the full range of particle sizes was carried out on 16 processes in
      six different General Motors plants over a period of 2.5 years. This article
      deals with particle characterization from five of the processes that relate to
      machining, specifically, wet machining with water-based fluids from old and new
      technology processes, grinding with straight oils from old and new technology
      processes, and dry machining. The concentrations measured by different
      instruments were in reasonable agreement, although the light-scattering
      instrument generally produced higher values than filters. Of the processes
      studied, the old technology grinding using straight oils generated the highest
      particle concentrations. The new technology controls (enclosed, vented machines)
      were highly effective but more so for large particles than small particles. The
      particle size distribution was shifted to smaller particles with enclosed
      processes. Dry machining generated the largest particles of all processes
      studied.

PMID- 16282166
TI  - Assessment of fungal growth on sodium polyborate-treated cellulose insulation.
AB  - Cellulose insulation has rapidly gained a large market share among general
      contractors and homeowners. Recent interest regarding health effects of high
      concentrations of fungi within indoor environments (building-related illnesses or
      sick building syndrome) has promoted concern about susceptibility of building
      materials, including wood products (in general) and cellulose insulation
      (specifically), to fungal attack. This study reports an assessment of fungal
      growth on cellulose insulation made from recycled paper and treated with varying
      concentrations of sodium polyborate within half-scale wall units exposed to
      variable and high ambient temperatures and relative humidities throughout the
      summer. Boron-treated and untreated (control) cellulose insulation within the
      wall units were challenged with a suspension containing high concentrations of
      spores of five fungal species commonly found in indoor environments. Our results
      suggest that cellulose insulation treated with sodium polyborate (a) precludes
      the growth of the five common fungal species; (b) harbors fewer fungal species
      before and after being challenged with the fungal spore suspension; and (c) is
      likely having a cytotoxic or sporocidal effect on many, if not all, fungal
      species. These results suggest that cellulose insulation treated with sodium
      polyborate, when properly applied and installed, precludes fungal growth for at
      least 124 days at high temperatures and relative humidities.

PMID- 16282167
TI  - Mosaics of convergences and noise in morphological phylogenies: what's in a
      viverrid-like carnivoran?
AB  - Adaptive convergence in morphological characters has not been thoroughly
      investigated, and the processes by which phylogenetic relationships may be misled
      by morphological convergence remains unclear. We undertook a case study on the
      morphological evolution of viverrid-like feliformians (Nandinia, Cryptoprocta,
      Fossa, Eupleres, Prionodon) and built the largest morphological matrix concerning
      the suborder Feliformia to date. A total of 349 characters grouped into four
      anatomical partitions were used for all species of Viverridae and viverrid-like
      taxa plus representatives of the Felidae, Hyaenidae, Herpestidae, and one
      Malagasy mongoose. Recent molecular phylogenetic analyses suggest that viverrid
      like morphotypes appeared independently at least three times during feliformian
      evolution. We thus used a synthetic molecular tree to assess morphological
      evolutionary patterns characterizing the viverrid-like taxa. We examined
      phylogenetic signal, convergence and noise in morphological characters using (a)
      tree-length distribution (g1), (b) partitioned Bremer support, (c) RI values and
      their distribution, (d) respective contributions of diagnostic synapomorphies at
      the nodes for each partition, (e) patterns of shared convergences among viverrid
      like taxa and other feliformian lineages, (f) tree-length differences among
      alternative hypotheses, and (g) the successive removal of convergent character
      states from the original matrix. In addition, the lability of complex
      morphological structures was assessed by mapping them onto the synthetic
      molecular tree. The unconstrained morphological analysis yielded phylogenetic
      groupings that closely reflected traditional classification. The use of a
      synthetic molecular tree (constraint) combined with our thorough morphological
      investigations revealed the mosaics of convergences likely to have contributed to
      part of the historical uncertainty over viverrid classification. It also showed
      that complex morphological structures could be subjected to reversible
      evolutionary trends. The morphological matrix proved useful in characterizing
      several feliformian clades with diagnostic synapomorphies. These results support
      the removal from the traditionally held Viverridae of several viverrid-like taxa
      into three distinct families: Nandiniidae (Nandinia), Prionodontidae (Prionodon),
      and the newly defined Eupleridae (including Cryptoprocta, Fossa, Eupleres plus
      all "mongoose-like" Malagasy taxa). No clearly "phylogenetically misleading" data
      subsets could be identified, and the great majority of morphological convergences
      appeared to be nonadaptive. The multiple approaches used in this study revealed
      that the most disruptive element with regards to morphological phylogenetic
      reconstruction was noise, which blured the expression of phylogenetic signal.
      This study demonstrates the crucial need to consider independent (molecular)
      phylogenies in order to produce reliable evolutionary hypotheses and should
      promote a new approach to the definition of morphological characters in mammals.
      [Constrained analysis; convergence; evolutionary scenario; Feliformia;
      morphology; noise; phylogenetic signal; phylogeny; Viverridae.].

PMID- 16282168
TI  - Nodes in phylogenetic trees: the relation between imbalance and number of
      descendent species.
AB  - The imbalance of a node in a phylogenetic tree can be defined in terms of the
      relative numbers of species (or higher taxa) on the branches that originate at
      the node. Empirically, imbalance also turns out to depend on the absolute total
      number of species on the branches: in a sample of large trees, nodes with more
      descendent species tend to be more unbalanced. Subsidiary analyses suggest that
      this pattern is not a result of errors in tree estimation. Instead, the increase
      in imbalance with species is consistent with a cumulative effect of differences
      in diversification rates between branches. [Equal-rates Markov model; imbalance;
      phylogeny shape; proportional-to-distinguishable-arrangements model.].

PMID- 16282169
TI  - Calculating the evolutionary rates of different genes: a fast, accurate estimator
      with applications to maximum likelihood phylogenetic analysis.
AB  - In phylogenetic analyses with combined multigene or multiprotein data sets,
      accounting for differing evolutionary dynamics at different loci is essential for
      accurate tree prediction. Existing maximum likelihood (ML) and Bayesian
      approaches are computationally intensive. We present an alternative approach that
      is orders of magnitude faster. The method, Distance Rates (DistR), estimates
      rates based upon distances derived from gene/protein sequence data. Simulation
      studies indicate that this technique is accurate compared with other methods and
      robust to missing sequence data. The DistR method was applied to a fungal
      mitochondrial data set, and the rate estimates compared well to those obtained
      using existing ML and Bayesian approaches. Inclusion of the protein rates
      estimated from the DistR method into the ML calculation of trees as a branch
      length multiplier resulted in a significantly improved fit as measured by the
      Akaike Information Criterion (AIC). Furthermore, bootstrap support for the ML
      topology was significantly greater when protein rates were used, and some evident
      errors in the concatenated ML tree topology (i.e., without protein rates) were
      corrected. [Bayesian credible intervals; DistR method; multigene phylogeny;
      PHYML; rate heterogeneity.].

PMID- 16282170
TI  - Images in clinical medicine. Cetuximab-associated acneiform eruption.

PMID- 16282171
TI  - Recertification for internists--one "grandfather's" experience.

PMID- 16282172
TI  - Personal metrics for practice--how'm I doing?

PMID- 16282173
TI  - Renewing board certification.

PMID- 16282174
TI  - Glioblastoma multiforme and the epidermal growth factor receptor.

PMID- 16282175
TI  - First-trimester or second-trimester screening, or both, for Down's syndrome.
AB  - BACKGROUND: It is uncertain how best to screen pregnant women for the presence of
      fetal Down's syndrome: to perform first-trimester screening, to perform second
      trimester screening, or to use strategies incorporating measurements in both
      trimesters. METHODS: Women with singleton pregnancies underwent first-trimester
      combined screening (measurement of nuchal translucency, pregnancy-associated
      plasma protein A [PAPP-A], and the free beta subunit of human chorionic
      gonadotropin at 10 weeks 3 days through 13 weeks 6 days of gestation) and second
      trimester quadruple screening (measurement of alpha-fetoprotein, total human
      chorionic gonadotropin, unconjugated estriol, and inhibin A at 15 through 18
      weeks of gestation). We compared the results of stepwise sequential screening
      (risk results provided after each test), fully integrated screening (single risk
      result provided), and serum integrated screening (identical to fully integrated
      screening, but without nuchal translucency). RESULTS: First-trimester screening
      was performed in 38,167 patients; 117 had a fetus with Down's syndrome. At a 5
      percent false positive rate, the rates of detection of Down's syndrome were as
      follows: with first-trimester combined screening, 87 percent, 85 percent, and 82
      percent for measurements performed at 11, 12, and 13 weeks, respectively; with
      second-trimester quadruple screening, 81 percent; with stepwise sequential
      screening, 95 percent; with serum integrated screening, 88 percent; and with
      fully integrated screening with first-trimester measurements performed at 11
      weeks, 96 percent. Paired comparisons found significant differences between the
      tests, except for the comparison between serum integrated screening and combined
      screening. CONCLUSIONS: First-trimester combined screening at 11 weeks of
      gestation is better than second-trimester quadruple screening but at 13 weeks has
      results similar to second-trimester quadruple screening. Both stepwise sequential
      screening and fully integrated screening have high rates of detection of Down's
      syndrome, with low false positive rates.

PMID- 16282176
TI  - Molecular determinants of the response of glioblastomas to EGFR kinase
      inhibitors.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) is frequently amplified,
      overexpressed, or mutated in glioblastomas, but only 10 to 20 percent of patients
      have a response to EGFR kinase inhibitors. The mechanism of responsiveness of
      glioblastomas to these inhibitors is unknown. METHODS: We sequenced kinase
      domains in the EGFR and human EGFR type 2 (Her2/neu) genes and analyzed the
      expression of EGFR, EGFR deletion mutant variant III (EGFRvIII), and the tumor
      suppressor protein PTEN in recurrent malignant gliomas from patients who had
      received EGFR kinase inhibitors. We determined the molecular correlates of
      clinical response, validated them in an independent data set, and identified
      effects of the molecular abnormalities in vitro. RESULTS: Of 49 patients with
      recurrent malignant glioma who were treated with EGFR kinase inhibitors, 9 had
      tumor shrinkage of at least 25 percent. Pretreatment tissue was available for
      molecular analysis from 26 patients, 7 of whom had had a response and 19 of whom
      had rapid progression during therapy. No mutations in EGFR or Her2/neu kinase
      domains were detected in the tumors. Coexpression of EGFRvIII and PTEN was
      significantly associated with a clinical response (P<0.001; odds ratio, 51; 95
      percent confidence interval, 4 to 669). These findings were validated in 33
      patients who received similar treatment for glioblastoma at a different
      institution (P=0.001; odds ratio, 40; 95 percent confidence interval, 3 to 468).
      In vitro, coexpression of EGFRvIII and PTEN sensitized glioblastoma cells to
      erlotinib. CONCLUSIONS: Coexpression of EGFRvIII and PTEN by glioblastoma cells
      is associated with responsiveness to EGFR kinase inhibitors.

PMID- 16282177
TI  - Continuous positive airway pressure for central sleep apnea and heart failure.
AB  - BACKGROUND: The Canadian Continuous Positive Airway Pressure for Patients with
      Central Sleep Apnea and Heart Failure trial tested the hypothesis that continuous
      positive airway pressure (CPAP) would improve the survival rate without heart
      transplantation of patients who have central sleep apnea and heart failure.
      METHODS: After medical therapy was optimized, 258 patients who had heart failure
      (mean age [+/-SD], 63+/-10 years; ejection fraction, 24.5+/-7.7 percent) and
      central sleep apnea (number of episodes of apnea and hypopnea per hour of sleep,
      40+/-16) were randomly assigned to receive CPAP (128 patients) or no CPAP (130
      patients) and were followed for a mean of two years. During follow-up, sleep
      studies were conducted and measurements of the ejection fraction, exercise
      capacity, quality of life, and neurohormones were obtained. RESULTS: Three months
      after undergoing randomization, the CPAP group, as compared with the control
      group, had greater reductions in the frequency of episodes of apnea and hypopnea
      (-21+/-16 vs. -2+/-18 per hour, P<0.001) and in norepinephrine levels (-1.03+/
      1.84 vs. 0.02+/-0.99 nmol per liter, P=0.009), and greater increases in the mean
      nocturnal oxygen saturation (1.6+/-2.8 percent vs. 0.4+/-2.5 percent, P<0.001),
      ejection fraction (2.2+/-5.4 percent vs. 0.4+/-5.3 percent, P=0.02), and the
      distance walked in six minutes (20.0+/-55 vs. -0.8+/-64.8 m, P=0.016). There were
      no differences between the control group and the CPAP group in the number of
      hospitalizations, quality of life, or atrial natriuretic peptide levels. An early
      divergence in survival rates without heart transplantation favored the control
      group, but after 18 months the divergence favored the CPAP group, yet the overall
      event rates (death and heart transplantation) did not differ (32 vs. 32 events,
      respectively; P=0.54). CONCLUSIONS: Although CPAP attenuated central sleep apnea,
      improved nocturnal oxygenation, increased the ejection fraction, lowered
      norepinephrine levels, and increased the distance walked in six minutes, it did
      not affect survival. Our data do not support the use of CPAP to extend life in
      patients who have central sleep apnea and heart failure.

PMID- 16282178
TI  - Obstructive sleep apnea as a risk factor for stroke and death.
AB  - BACKGROUND: Previous studies have suggested that the obstructive sleep apnea
      syndrome may be an important risk factor for stroke. It has not been determined,
      however, whether the syndrome is independently related to the risk of stroke or
      death from any cause after adjustment for other risk factors, including
      hypertension. METHODS: In this observational cohort study, consecutive patients
      underwent polysomnography, and subsequent events (strokes and deaths) were
      verified. The diagnosis of the obstructive sleep apnea syndrome was based on an
      apnea-hypopnea index of 5 or higher (five or more events per hour); patients with
      an apnea-hypopnea index of less than 5 served as the comparison group.
      Proportional-hazards analysis was used to determine the independent effect of the
      obstructive sleep apnea syndrome on the composite outcome of stroke or death from
      any cause. RESULTS: Among 1022 enrolled patients, 697 (68 percent) had the
      obstructive sleep apnea syndrome. At baseline, the mean apnea-hypopnea index in
      the patients with the syndrome was 35, as compared with a mean apnea-hypopnea
      index of 2 in the comparison group. In an unadjusted analysis, the obstructive
      sleep apnea syndrome was associated with stroke or death from any cause (hazard
      ratio, 2.24; 95 percent confidence interval, 1.30 to 3.86; P=0.004). After
      adjustment for age, sex, race, smoking status, alcohol-consumption status, body
      mass index, and the presence or absence of diabetes mellitus, hyperlipidemia,
      atrial fibrillation, and hypertension, the obstructive sleep apnea syndrome
      retained a statistically significant association with stroke or death (hazard
      ratio, 1.97; 95 percent confidence interval, 1.12 to 3.48; P=0.01). In a trend
      analysis, increased severity of sleep apnea at baseline was associated with an
      increased risk of the development of the composite end point (P=0.005).
      CONCLUSIONS: The obstructive sleep apnea syndrome significantly increases the
      risk of stroke or death from any cause, and the increase is independent of other
      risk factors, including hypertension.

PMID- 16282180
TI  - Images in clinical medicine. Renal colic.

PMID- 16282179
TI  - Acute oxygen-sensing mechanisms.

PMID- 16282181
TI  - Case records of the Massachusetts General Hospital. Case 34-2005. A 10-year-old
      girl with a bullous skin eruption and acute respiratory failure.

PMID- 16282182
TI  - Choosing the best prenatal screening protocol.

PMID- 16282183
TI  - Sleep--a new cardiovascular frontier.

PMID- 16282184
TI  - Health-information altruists--a potentially critical resource.

PMID- 16282185
TI  - One commensal bacterial molecule--all we need for health?

PMID- 16282186
TI  - Trends in racial disparities in care.

PMID- 16282187
TI  - Costimulation blockade with belatacept in renal transplantation.

PMID- 16282188
TI  - CD3-antibody therapy in new-onset type 1 diabetes mellitus.

PMID- 16282189
TI  - Post-transplantation proteinuria and sirolimus.

PMID- 16282190
TI  - Retinoid X receptor heterodimers in the metabolic syndrome.

PMID- 16282191
TI  - . . . And a diagnostic test was performed.

PMID- 16282192
TI  - Preliminary assessment of the efficacy, tolerability and safety of a cannabis
      based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis.
AB  - OBJECTIVES: To assess the efficacy of a cannabis-based medicine (CBM) in the
      treatment of pain due to rheumatoid arthritis (RA). METHODS: We compared a CBM
      (Sativex) with placebo in a randomized, double-blind, parallel group study in 58
      patients over 5 weeks of treatment. The CBM was administered by oromucosal spray
      in the evening and assessments were made the following morning. Efficacy outcomes
      assessed were pain on movement, pain at rest, morning stiffness and sleep quality
      measured by a numerical rating scale, the Short-Form McGill Pain Questionnaire
      (SF-MPQ) and the DAS28 measure of disease activity. RESULTS: Seventy-five
      patients were screened and 58 met the eligibility criteria. Thirty-one were
      randomized to the CBM and 27 to placebo. Mean (S.D.) daily dose achieved in the
      final treatment week was 5.4 (0.84) actuations for the CBM and 5.3 (1.18) for
      placebo. In comparison with placebo, the CBM produced statistically significant
      improvements in pain on movement, pain at rest, quality of sleep, DAS28 and the
      SF-MPQ pain at present component. There was no effect on morning stiffness but
      baseline scores were low. The large majority of adverse effects were mild or
      moderate, and there were no adverse effect-related withdrawals or serious adverse
      effects in the active treatment group. CONCLUSIONS: In the first ever controlled
      trial of a CBM in RA, a significant analgesic effect was observed and disease
      activity was significantly suppressed following Sativex treatment. Whilst the
      differences are small and variable across the population, they represent benefits
      of clinical relevance and show the need for more detailed investigation in this
      indication.

PMID- 16282193
TI  - Stretch increases alveolar epithelial permeability to uncharged micromolecules.
AB  - We measured stretch-induced changes in transepithelial permeability in vitro to
      uncharged tracers 1.5-5.5 A in radius to identify a critical stretch threshold
      associated with failure of the alveolar epithelial transport barrier. Cultured
      alveolar epithelial cells were subjected to a uniform cyclic (0.25 Hz) biaxial
      12, 25, or 37% change in surface area (DeltaSA) for 1 h. Additional cells served
      as unstretched controls. Only 37% DeltaSA (100% total lung capacity) produced a
      significant increase in transepithelial tracer permeability, with the largest
      increases for bigger tracers. Using the permeability data, we modeled the
      epithelial permeability in each group as a population of small pores punctuated
      by occasional large pores. After 37% DeltaSA, increases in paracellular transport
      were correlated with increases in the radii of both pore populations. Inhibition
      of protein kinase C and tyrosine kinase activity during stretch did not affect
      the permeability of stretched cells. In contrast, chelating intracellular calcium
      and/or stabilizing F-actin during 37% DeltaSA stretch reduced but did not
      eliminate the stretch-induced increase in paracellular permeability. These
      results provide the first in vitro evidence that large magnitudes of stretch
      increase paracellular transport of micromolecules across the alveolar epithelium,
      partially mediated by intracellular signaling pathways. Our monolayer data are
      supported by whole lung permeability results, which also show an increase in
      alveolar permeability at high inflation volumes (20 ml/kg) at the same rate for
      both healthy and septic lungs.

PMID- 16282194
TI  - Norepinephrine activates store-operated Ca2+ entry coupled to large-conductance
      Ca2+-activated K+ channels in rat pinealocytes.
AB  - Norepinephrine (NE) is one of the major neurotransmitters that determine
      melatonin production in the pineal gland. Although a substantial amount of Ca(2+)
      influx is triggered by NE, the Ca(2+) entry pathway and its physiological
      relevance have not been elucidated adequately. Herein we report that the Ca(2+)
      influx triggered by NE significantly regulates the protein level of serotonin N
      acetyltransferase, or arylalkylamine N-acetyltransferase (AANAT), a critical
      enzyme in melatonin production, and is responsible for maintaining the Ca(2+)
      response after repetitive stimulation. Ca(2+) entry evoked by NE was dependent on
      PLC activation. NE evoked a substantial amount of Ca(2+) entry even after cells
      were treated with 1-oleoyl-2-acetyl-sn-glycerol (OAG), an analog of
      diacylglycerol. To the contrary, further OAG treatment after cells had been
      exposed to OAG did not evoke additional Ca(2+) entry. Moreover, NE failed to
      induce further Ca(2+) entry after the development of Ca(2+) entry induced by
      thapsigargin (Tg), suggesting that the pathway of Ca(2+) entry induced by NE
      might be identical to that of Tg. Interestingly, Ca(2+) entry evoked by NE or Tg
      induced membrane hyperpolarization that was reversed by iberiotoxin (IBTX), a
      specific inhibitor of large-conductance Ca(2+)-activated K(+) (BK) channels.
      Moreover, IBTX-sensitive BK current was observed during application of NE,
      suggesting that activation of the BK channels was responsible for the
      hyperpolarization. Furthermore, the activation of BK channels triggered by NE
      contributed to regulation of the protein level of AANAT. Collectively, these
      results suggest that NE triggers Ca(2+) entry coupled to BK channels and that NE
      induced Ca(2+) entry is important in the regulation of AANAT.

PMID- 16282195
TI  - The depressive effect of Pi on the force-pCa relationship in skinned single
      muscle fibers is temperature dependent.
AB  - Increases in P(i) combined with decreases in myoplasmic Ca(2+) are believed to
      cause a significant portion of the decrease in muscular force during fatigue. To
      investigate this further, we determined the effect of 30 mM P(i) on the force
      Ca(2+) relationship of chemically skinned single muscle fibers at near
      physiological temperature (30 degrees C). Fibers isolated from rat soleus (slow)
      and gastrocnemius (fast) muscle were subjected to a series of solutions with an
      increasing free Ca(2+) concentration in the presence and absence of 30 mM P(i) at
      both low (15 degrees C) and high (30 degrees C) temperature. In slow fibers, 30
      mM P(i) significantly increased the Ca(2+) required to elicit measurable force,
      referred to as the activation threshold at both low and high temperatures;
      however, the effect was twofold greater at the higher temperature. In fast
      fibers, the activation threshold was unaffected by elevating P(i) at 15 degrees C
      but was significantly increased at 30 degrees C. At both low and high
      temperatures, 30 mM P(i) increased the Ca(2+) required to elicit half-maximal
      force (pCa(50)) in both slow and fast fibers, with the effect of P(i) twofold
      greater at the higher temperature. These data suggest that during fatigue,
      reductions in the myoplasmic Ca(2+) and increases in P(i) act synergistically to
      reduce muscular force. Consequently, the combined changes in these ions likely
      account for a greater portion of fatigue than previously predicted based on
      studies at lower temperatures or high temperatures at saturating Ca(2+) levels.

PMID- 16282196
TI  - HMGB1 is secreted by immunostimulated enterocytes and contributes to cytomix
      induced hyperpermeability of Caco-2 monolayers.
AB  - High-mobility group box 1 (HMGB1), a cytokine-like proinflammatory protein, is
      secreted by activated macrophages and released by necrotic cells. We hypothesized
      that immunostimulated enterocytes might be another source for this mediator.
      Accordingly, Caco-2 cells or primary mouse intestinal epithelial cells (IECs)
      were incubated with "cytomix" (a mixture of TNF, IL-1beta, and IFN-gamma) for
      various periods. HMGB1 in cell culture supernatants was detected by Western blot
      analysis and visualized in Caco-2 cells with the use of fluorescence confocal and
      immunotransmission electron microscopy. Caco-2 cells growing on filters in
      diffusion chambers were stimulated with cytomix for 48 h in the absence or
      presence of anti-HMGB1 antibody, and permeability to fluorescein isothiocyanate
      dextran (average molecular mass, 4 kDa; FD4) was assessed. Cytomix-stimulated
      Caco-2 cells secreted HMGB1 into the apical but not the basolateral compartments
      of diffusion chambers. Although undetectable at 6 and 12 h after the start of
      incubation with cytomix, HMGB1 was present in supernatants after 24 h of
      incubation. HMGB1 secretion by Caco-2 monolayers also was induced when the cells
      were exposed to FSL-1, a Toll-like receptor (Tlr)-2 agonist, or flagellin, a Tlr5
      agonist, but not lipopolysaccharide, a Tlr4 agonist. Cytomix also induced HMGB1
      secretion by primary IECs. Cytoplasmic HMGB1 is localized within vesicles in Caco
      2 cells and is secreted, at least in part, associated with exosomes. Incubating
      Caco-2 cells with cytomix increased FD4 permeation, but this effect was
      significantly decreased in the presence of anti-HMGB1 antibody. Collectively,
      these data support the view that HMGB1 is secreted by immunostimulated
      enterocytes. This process may exacerbate inflammation-induced epithelial
      hyperpermeability via an autocrine feedback loop.

PMID- 16282197
TI  - Hypertonic saline enhances neutrophil elastase release through activation of P2
      and A3 receptors.
AB  - Hypertonic saline (HS) holds promise as a novel resuscitation fluid for the
      treatment of trauma patients because HS inhibits polymorphonuclear neutrophil
      (PMN) activation and thereby prevents host tissue damage and associated
      posttraumatic complications. However, depending on conditions of cell activation,
      HS can increase PMN degranulation, which could exacerbate tissue damage in trauma
      victims. The cellular mechanism by which HS increases degranulation is unknown.
      In the present study, we tested whether HS-induced ATP release from PMN and
      feedback via P1 and/or P2 receptors may be involved in the enhancement of
      degranulation by HS. We found that HS enhances elastase release and ERK and p38
      MAPK activation when HS is added after activation of PMN with formyl peptide
      (fMLP) or phorbol ester (PMA). Agonists of P2 nucleotide and A3 adenosine
      receptors mimicked these enhancing effects of HS, whereas antagonists of A3
      receptors or removal of extracellular ATP with apyrase diminished the response to
      HS. A1 adenosine receptor antagonists increased the enhancing effect of HS,
      whereas A1 receptor agonists inhibited elastase release. These data suggest that
      HS upregulates degranulation via ATP release and positive feedback through P2 and
      A3 receptors. We propose that these feedback mechanisms can serve as potential
      pharmacological targets to fine-tune the clinical effectiveness of HS
      resuscitation.

PMID- 16282198
TI  - Modulation of alpha7-integrin-mediated adhesion and expression by platelet
      derived growth factor in vascular smooth muscle cells.
AB  - We showed previously that the expression of alpha(7)-integrin in aortic vascular
      smooth muscle cells (VSMC) is enhanced in a rat model of atherosclerosis. In the
      present study, we investigated the effects of platelet-derived growth factor
      (PDGF) on alpha(7)-integrin expression and VSMC adhesion and migration.
      Expression of the alpha(7)-integrin gene was determined by real-time RT-PCR,
      whereas protein levels were determined by fluorescence-activated cell sorting
      analysis. PDGF increased alpha(7) cell surface protein expression (12 and 24 h:
      3.3 +/- 0.8- and 3.6 +/- 0.4-fold, P < 0.05 vs. control) and mRNA levels (24 h:
      3.1-fold, P < 0.05 vs. control) in a time-dependent manner. Actinomycin D and
      cycloheximide attenuated PDGF-induced increases in alpha(7)-integrin, indicating
      the involvement of de novo mRNA and protein synthesis. Treatment with the MAPK
      inhibitors PD-98059, SP-600125, and SB-203580 attenuated PDGF-induced increases
      in mRNA. In contrast, PD-98059 and SP-600125, but not SB-203580, attenuated PDGF
      induced increases in cell surface protein levels. PDGF-treated VSMC adhered to
      laminin more efficiently (42 +/- 6% increase, P < 0.01), and this increase was
      partially inhibited by anti-alpha(7)-integrin function-blocking antibody.
      However, PDGF did not alter migration on laminin, and there was no effect of the
      anti-alpha(7)-integrin function-blocking antibody on basal or PDGF-stimulated
      migration. Immunofluorescence imaging revealed an increase in alpha(7)-integrin
      distribution along the stress fibers. Together, these observations indicate that
      PDGF enhances alpha(7)-integrin expression in VSMC and promotes alpha(7)-integrin
      mediated adhesion to laminin.

PMID- 16282199
TI  - Dopamine modulation of honey bee (Apis mellifera) antennal-lobe neurons.
AB  - Primary olfactory centers [antennal lobes (ALs)] of the honey bee brain are
      invaded by dopamine (DA)-immunoreactive neurons early in development (pupal stage
      3), immediately before a period of rapid growth and compartmentalization of the
      AL neuropil. Here we examine the modulatory actions of DA on honey bee AL neurons
      during this period. Voltage-clamp recordings in whole cell configuration were
      used to determine the effects of DA on ionic currents in AL neurons in vitro from
      pupal bees at stages 4-6 of the nine stages of metamorphic adult development. In
      approximately 45% of the neurons tested, DA (5-50 x 10(-5) M) reduced the
      amplitude of outward currents in the cells. In addition to a slowly activating,
      sustained outward current, DA reduced the amplitude of a rapidly activating,
      transient outward conductance in some cells. Both of the currents modulated by DA
      could be abolished by the removal of Ca2+ from the external medium or by
      treatment of cells with charybdotoxin (2 x 10(-8) M), a blocker of Ca2+-dependent
      K+ currents in the cells. Ca2+ currents were not affected by DA, nor were A-type
      K+ currents (I(A)). Results suggest that the delayed rectifier-like current
      (I(KV)) also remains intact in the presence of DA. Taken together, our data
      indicate that Ca2+-dependent K+ currents are targets of DA modulation in honey
      bee AL neurons. This study lends support to the hypothesis that DA plays a role
      in the developing brain of the bee.

PMID- 16282200
TI  - Prolonged vibration of the biceps brachii tendon reduces time to failure when
      maintaining arm position with a submaximal load.
AB  - Vibration reduces the amplitudes of the tendon jerk response and the Hoffmann and
      stretch reflexes in the muscle exposed to the vibration, yet does not alter the
      time to task failure when the task involves exerting a submaximal force against a
      rigid restraint. Because the amplitude of the stretch reflex is greater when a
      limb acts against a compliant load than a rigid restraint, the purpose was to
      determine the influence of prolonged tendon vibration on the time to failure when
      maintaining limb position with the elbow flexor muscles. Twenty-five healthy men
      performed the fatiguing contraction by maintaining elbow angle at 1.57 rad until
      failure while supporting a load equal to 20% of maximal voluntary contraction
      (MVC) force. The fatiguing contraction was performed on 3 separate days with
      different levels of vibration applied to the biceps brachii tendon: no vibration,
      subthreshold for a tonic vibration reflex (TVR), and suprathreshold for a TVR.
      MVC force before the fatiguing contraction was similar across the three sessions
      (mean of 3 sessions: 313 +/- 54 N, P = 0.83). Despite a similar decline in MVC
      force after the fatiguing contraction across conditions (-18.0 +/- 8.0%, P >
      0.05), the time to task failure was 3.7 +/- 1.4 min for the suprathreshold TVR
      condition, 4.3 +/- 2.1 min for the subthreshold TVR condition, and 5.0 +/- 2.2
      min for the no-vibration condition (P < 0 0.001). The average EMG of the elbow
      flexor muscles was similar (P = 0.22) during the fatiguing contractions. However,
      the fluctuations in limb acceleration at task onset were greater for the
      suprathreshold TVR condition (P < 0.01), but were not different between the
      subthreshold TVR and no-vibration conditions (P > or = 0.22). Furthermore, the
      difference in the SD of limb acceleration between the no-vibration and vibration
      conditions was correlated with the difference in time to failure for the no
      vibration and subthreshold TVR conditions (P = 0.03; r2 = 0.22), but not for the
      no-vibration and suprathreshold TVR conditions (P = 0.90; r2 = 0.001). These
      findings indicate that prolonged vibration reduced the time to failure of a
      sustained contraction when subjects maintained limb position, suggesting that
      peripheral inputs to the motor neuron pool play a significant role in sustaining
      a contraction during tasks that require active control of limb position.

PMID- 16282201
TI  - Dynamics of pain: fractal dimension of temporal variability of spontaneous pain
      differentiates between pain States.
AB  - Spontaneous pain is a common complaint in chronic pain conditions. However, its
      properties have not been explored. Here we study temporal properties of
      spontaneous pain. We examine time variability of fluctuations of spontaneous pain
      in patients suffering from chronic back pain and chronic postherpetic neuropathy
      and contrast properties of these ratings to normal subjects' ratings of either
      acute thermal painful stimuli or of imagined back pain. Subjects are instructed
      to continuously rate their subjective assessment of the intensity of pain over a
      6- to 12-min period. We observe that the fluctuations of spontaneous pain do not
      possess stable mean or variance, implying that these time series can be better
      characterized by fractal analysis. To this end, we apply time and frequency
      domain techniques to characterize variability of pain ratings with a single
      parameter: fractal dimension, D. We demonstrate that the majority of ratings of
      spontaneous pain by the patients have fractal properties, namely they show a
      power law relationship between variability and time-scale length; D is distinct
      between types of chronic pain, and from ratings of thermal stimulation or of
      imagined pain; and there is a correspondence between D for pain ratings and D for
      brain activity, in chronic back pain patients using fMRI. These results show that
      measures of variability of spontaneous pain differentiate between chronic pain
      conditions, and thus may have mechanistic and clinical utility.

PMID- 16282202
TI  - Spinal cord maps of spatiotemporal alpha-motoneuron activation in humans walking
      at different speeds.
AB  - Functional MRI (fMRI) imaging of motoneuron activity in the human spinal cord is
      still in its infancy, and it will remain difficult to apply to walking. Here we
      present a viable alternative for documenting the spatiotemporal maps of alpha
      motorneuron (MN) activity in the human spinal cord during walking, similar to the
      method recently reported for the cat. We recorded EMG activity from 16 to 32
      ipsilateral limb and trunk muscles in 13 healthy subjects walking on a treadmill
      at different speeds (1-7 km/h) and mapped the recorded patterns onto the spinal
      cord in approximate rostrocaudal locations of the motoneuron pools. This approach
      can provide information about pattern generator output during locomotion in terms
      of segmental control rather than in terms of individual muscle control. A
      striking feature we found is that nearly every spinal segment undergoes at least
      two cycles of activation in the step cycle, thus supporting the idea of half
      center oscillators controlling MN activation at any segmental level. The
      resulting spatiotemporal map patterns seem highly stereotyped over the range of
      walking speeds studied, although there were also some systematic redistributions
      of MN activity with speed. Bursts of MN activity were either temporally aligned
      across several spinal segments or switched between different segments. For
      example, the center of mass of MN activity in the lumbosacral levels generally
      shifted from rostral to caudal positions in two cycles for each step, revealing
      four major activation foci: two in the upper lumbar segments and two in the
      sacral segments. The results are consistent with the presence of at least two and
      possibly more pattern generators controlling the activation of lumbosacral MNs.

PMID- 16282203
TI  - Epileptogenesis is associated with enhanced glutamatergic transmission in the
      perforant path.
AB  - The perforant path provides the main excitatory input into the hippocampus and
      has been proposed to play a critical role in the generation of temporal lobe
      seizures. It has been hypothesized that changes in glutamatergic transmission in
      this pathway promote the epileptogenic process and seizure generation. We
      therefore asked whether epileptogenesis is associated with enhanced glutamatergic
      transmission from the perforant path to dentate granule cells. We used a rat
      model of temporal lobe epilepsy in which spontaneous seizures occur after an
      episode of pilocarpine-induced status epilepticus. Whole cell patch-clamp
      recordings were obtained from dentate granule cells in hippocampal slices from
      control and epileptic animals 3 wk after pilocarpine-induced status epilepticus.
      The paired pulse ratio of perforant path-evoked AMPA receptor-mediated excitatory
      postsynaptic currents (EPSCs) was reduced in tissue obtained from epileptic rats.
      This is consistent with an increase in release probability. N-methyl-d-aspartate
      (NMDA) receptor-mediated EPSCs were also prolonged. This prolongation could not
      be accounted for by decreased activity of glutamate transporters or by a change
      in NMDA receptor subunit composition in dentate granule cells, implying a change
      in NMDA receptor kinetics. This change in NMDA receptor kinetics was associated
      with the emergence of significant synaptic cross-talk, detected as a use
      dependent block of receptors activated by medial perforant path synapses after
      lateral perforant path stimulation in MK-801. Enhanced glutamatergic transmission
      and the emergence of cross-talk among perforant path-dentate granule cell
      synapses may contribute to lowering seizure threshold.

PMID- 16282204
TI  - A quartet neural system model orchestrating sleep and wakefulness mechanisms.
AB  - Physiological knowledge of the neural mechanisms regulating sleep and wakefulness
      has been advanced by the recent findings concerning sleep/wakefulness-related
      preoptic/anterior hypothalamic and perifornical (orexin-containing)/posterior
      hypothalamic neurons. In this paper, we propose a mathematical model of the
      mechanisms orchestrating a quartet neural system of sleep and wakefulness
      composed of the following: 1) sleep-active preoptic/anterior hypothalamic neurons
      (N-R group); 2) wake-active hypothalamic and brain stem neurons exhibiting the
      highest rate of discharge during wakefulness and the lowest rate of discharge
      during paradoxical or rapid eye movement (REM) sleep (WA group); 3) brain stem
      neurons exhibiting the highest rate of discharge during REM sleep (REM group);
      and 4) basal forebrain, hypothalamic, and brain stem neurons exhibiting a higher
      rate of discharge during both wakefulness and REM sleep than during nonrapid eye
      movement (NREM) sleep (W-R group). The WA neurons have mutual inhibitory
      couplings with the REM and N-R neurons. The W-R neurons have mutual excitatory
      couplings with the WA and REM neurons. The REM neurons receive unidirectional
      inhibition from the N-R neurons. In addition, the N-R neurons are activated by
      two types of sleep-promoting substances (SPS), which play different roles in the
      homeostatic regulation of sleep and wakefulness. The model well reproduces the
      actual sleep and wakefulness patterns of rats in addition to the sleep-related
      neuronal activities across state transitions. In addition, human sleep
      wakefulness rhythms can be simulated by manipulating only a few model parameters:
      inhibitions from the N-R neurons to the REM and WA neurons are enhanced, and
      circadian regulation of the N-R and WA neurons is exaggerated. Our model could
      provide a novel framework for the quantitative understanding of the mechanisms
      regulating sleep and wakefulness.

PMID- 16282205
TI  - Tail muscles become slow but fatigable in chronic sacral spinal rats with
      spasticity.
AB  - Paralyzed skeletal muscle sometimes becomes faster and more fatigable after
      spinal cord injury (SCI) because of reduced activity. However, in some cases,
      pronounced muscle activity in the form of spasticity (hyperreflexia and
      hypertonus) occurs after long-term SCI. We hypothesized that this spastic
      activity may be associated with a reversal back to a slower, less fatigable
      muscle. In adult rats, a sacral (S2) spinal cord transection was performed,
      affecting only tail musculature and resulting in chronic tail spasticity
      beginning 2 wk later and lasting indefinitely. At 8 mo after injury, we examined
      the contractile properties of the segmental tail muscle in anesthetized spastic
      rats and in age-matched normal rats. The segmental tail muscle has only a few
      motor units (<12), which were easily detected with graded nerve stimulation,
      revealing two clear motor unit twitch durations. The dominant faster unit
      twitches peaked at 15 ms and ended within 50 ms, whereas the slower unit twitches
      only peaked at 30-50 ms. With chronic injury, this slow twitch component
      increased, resulting in a large overall increase (>150%) in the fraction of the
      peak muscle twitch force remaining at 50 ms. With injury, the peak muscle twitch
      (evoked with supramaximal stimulation) also increased in its time to peak
      (+48.9%) and half-rise time (+150.0%), and decreased in its maximum rise (-35.0%)
      and decay rates (-40.1%). Likewise, after a tetanic stimulation, the tetanus half
      fall time increased by 53.8%. Therefore the slow portion of the muscle was
      enhanced in spastic muscles. Consistent with slowing, posttetanic potentiation
      was 9.2% lower and the stimulation frequency required to produce half-maximal
      tetanus decreased 39.0% in chronic spinals. Interestingly, in spastic muscles
      compared with normal, whole muscle twitch force was 81.1% higher, whereas tetanic
      force production was 38.1% lower. Hence the twitch-to-tetanus ratio increased
      104.0%. Inconsistent with overall slowing, whole spastic muscles were 61.5% more
      fatigable than normal muscles. Thus contrary to the classical slow-to-fast
      conversion that is seen after SCI without spasticity, SCI with spasticity is
      associated with a mixed effect, including a preservation/enhancement of slow
      properties, but a loss of fatigue resistance.

PMID- 16282206
TI  - Persistent sodium currents and repetitive firing in motoneurons of the
      sacrocaudal spinal cord of adult rats.
AB  - Months after sacral spinal transection in rats (chronic spinal rats), motoneurons
      below the injury exhibit large, low-threshold persistent inward currents (PICs),
      composed of persistent sodium currents (Na PICs) and persistent calcium currents
      (Ca PICs). Here, we studied whether motoneurons of normal adult rats also
      exhibited Na and Ca PICs when the spinal cord was acutely transected at the
      sacral level (acute spinal rats) and examined the role of the Na PIC in firing
      behavior. Intracellular recordings were obtained from motoneurons of acute and
      chronic spinal rats while the whole sacrocaudal spinal cord was maintained in
      vitro. Compared with chronic spinal rats, motoneurons of acute spinal rats were
      more difficult to activate because the input resistance was 22% lower and resting
      membrane potential was hyperpolarized 4.1 mV further below firing threshold (
      50.9 +/- 6.2 mV). In acute spinal rats, during a slow voltage ramp, a PIC was
      activated subthreshold to the spike (at -57.2 +/- 5.0 mV) and reached a peak
      current of 1.11 +/- 1.21 nA. This PIC was less than one-half the size of that in
      chronic spinal rats (2.79 +/- 0.94 nA) and usually was not large enough to
      produce bistable behavior (plateau potentials and self-sustained firing not
      present), unlike in chronic spinal rats. The PIC was composed of two components:
      a TTX-sensitive Na PIC (0.44 +/- 0.36 nA) and a nimodipine-sensitive Ca PIC (0.78
      +/- 0.82 nA). Both were smaller than in chronic spinal rats (but with similar
      Na/Ca ratio). The presence of the Na PIC was critical for normal repetitive
      firing, because no detectable Na PIC was found in the few motoneurons that could
      not fire repetitively during a slow ramp current injection and motoneurons that
      had large Na PICs more readily produced repetitive firing and had lower minimum
      firing rates compared with neurons with small Na PICs. Furthermore, when the Na
      PIC was selectively blocked with riluzole, steady repetitive firing was
      eliminated, even though transient firing could be evoked on a rapid current step
      and the spike itself was unaffected. In summary, only small Ca and Na PICs occur
      in acute spinal motoneurons, but the Na PIC is essential for steady repetitive
      firing. We discuss how availability of monoamines may explain the variability in
      Na PICs and firing in the normal and spinal animals.

PMID- 16282207
TI  - Molecular characteristics of pbp1a and pbp2b in clinical Streptococcus pneumoniae
      isolates in Quebec, Canada.
AB  - OBJECTIVES: To investigate the nature of the amino acid motifs found in
      penicillin-binding protein (PBP) 2b and PBP1a of penicillin-resistant
      Streptococcus pneumoniae isolates across Quebec (Canada), and to obtain
      preliminary information regarding the prevalence of these alterations. METHODS:
      DNA sequences of pbp2b (codons 210-675) and pbp1a (codons 310-682) transpeptidase
      domains were determined and compared in 48 clinical isolates comprising 17
      penicillin-susceptible (PSSP), 19 penicillin-intermediate (PISP) and 12
      penicillin-resistant (PRSP) pneumococci. RESULTS: The degree of diversity within
      PBP1a and PBP2b correlated with increased resistance to beta-lactam antibiotics.
      There were an average of 0.6 +/- 0.4 and 2.9 +/- 0.2 mutations in PSSP, 16.8 +/-
      1.4 and 36.3 +/- 5.2 in PISP, and 18.7 +/- 2.5 and 51.4 +/- 1.3 in PRSP isolates
      compared with control penicillin-susceptible R6-PBP2b and R6-PBP1a sequences,
      respectively. At least seven PBP2b and six PBP1a distinct amino acid profiles
      were identified among intermediate or resistant strains isolated in Quebec. The
      pattern of distribution of the PBPs' altered amino acids differs from that of
      other countries, with pneumococci isolates from Quebec showing a unique genetic
      signature. CONCLUSION: This study will serve as a basis for future monitoring of
      genetic changes associated with the emergence and spread of beta-lactam
      resistance in Quebec, Canada.

PMID- 16282209
TI  - Does willingness to pay per quality-adjusted life year bring us closer to a
      useful decision rule for cost-effectiveness analysis?

PMID- 16282208
TI  - Rates of antifungal resistance among Spanish clinical isolates of Cryptococcus
      neoformans var. neoformans.
AB  - OBJECTIVES: Activities in vitro of six antifungal agents were tested against a
      collection of 317 Cryptococcus neoformans var. neoformans clinical isolates.
      METHODS: The procedure described in document 7.1 by the European Committee on
      Antibiotic Susceptibility Testing with minor modifications was employed. RESULTS:
      Amphotericin B, itraconazole, voriconazole and ravuconazole exhibited a potent
      activity with geometric mean (GM) MICs under 0.26 mg/L. The GM MIC of flucytosine
      was 7.33 mg/L and that of fluconazole was 4.16 mg/L. The rates of antifungal
      resistance were 5.3% for amphotericin B, 0.9% for voriconazole and 3.1% for
      ravuconazole. Fifteen point eight per cent of strains had itraconazole MICs > or
      = 1 mg/L, and 46% of strains had flucytosine MICs > or = 8 mg/L. Fluconazole
      susceptibility (MIC < or = 8 mg/L) stood at 53.4%. CONCLUSIONS: The percentage of
      fluconazole susceptibility was significantly lower than that in other surveys.
      Cross-resistance to itraconazole was common (33.8%) but almost the whole
      collection was susceptible to voriconazole and ravuconazole. These results should
      be confirmed with prospective and population-based surveillance programmes.

PMID- 16282210
TI  - Einstein on willingness to pay per QALY: is there a better way?

PMID- 16282211
TI  - Can prospect theory explain risk-seeking behavior by terminally ill patients?
AB  - Patients with life-threatening conditions sometimes appear to make risky
      treatment decisions as their condition declines, contradicting the risk-averse
      behavior predicted by expected utility theory. Prospect theory accommodates such
      decisions by describing how individuals evaluate outcomes relative to a reference
      point and how they exhibit risk-seeking behavior over losses relative to that
      point. The authors show that a patient's reference point for his or her health is
      a key factor in determining which treatment option the patient selects, and they
      examine under what circumstances the more risky option is selected. The authors
      argue that patients' reference points may take time to adjust following a change
      in diagnosis, with implications for predicting under what circumstances a patient
      may select experimental or conventional therapies or select no treatment.

PMID- 16282212
TI  - Cure me even if it kills me: preferences for invasive cancer treatment.
AB  - PURPOSE: When making medical decisions, people often care not only about what
      happens but also about whether the outcome was a result of actions voluntarily
      taken or a result of inaction. This study assessed the proportion of people
      choosing nonoptimal treatments (treatments which reduced survival chances) when
      presented with hypothetical cancer scenarios which varied by outcome cause.
      METHODS: A randomized survey experiment tested preferences for curing an existent
      cancer with 2 possible treatments (medication or surgery) and 2 effects of
      treatment (beneficial or harmful). Participants were 112 prospective jurors in
      the Philadelphia County Courthouse and 218 visitors to the Detroit-Wayne County
      Metropolitan Airport. RESULTS: When treatment was beneficial, 27% of participants
      rejected medication, whereas only 10% rejected surgery with identical outcomes (
      2 = 5.87, P < 0.02). When treatment was harmful, participants offered surgery
      were significantly more inclined to take action (65% v. 38%, chi(2) = 11.40, P =
      0.001), even though doing so reduced overall survival chances. CONCLUSIONS: Faced
      with hypothetical cancer diagnoses, many people say they would pursue treatment
      even if doing so would increase their chance of death. This tendency toward
      active treatment is notably stronger when the treatment offered is surgery
      instead of medication. Our study suggests that few people can imagine standing by
      and doing nothing after being diagnosed with cancer, and it should serve to
      remind clinicians that, for many patients, the best treatment alternative may not
      only depend on the medical outcomes they can expect to experience but also on
      whether those outcomes are achieved actively or passively.

PMID- 16282213
TI  - Incorporating biological natural history in simulation models: empirical
      estimates of the progression of end-stage liver disease.
AB  - OBJECTIVE: To develop an empiric natural-history model that can predict
      quantitative changes in the laboratory values and clinical characteristics of
      patients with end-stage liver disease (ESLD), to be used to calibrate an
      individual microsimulation model. METHODS: The authors report the development of
      a stochastic model that uses cubic splines to interpolate between observed
      laboratory values over time in a cohort of 1997 patients with ESLD awaiting liver
      transplantation at the University of Pittsburgh Medical Center. The splines were
      recursively sampled to provide a stochastic, quantitative natural history of each
      candidate's disease. RESULTS: The model was able to simulate the types of erratic
      disease trajectories that occur in individual patients and was able to preserve
      the statistical properties of the natural history of ESLD in cohorts of real
      patients. Moreover, the model was able to predict pretransplant survival rates
      (87% at 1 year), which were statistically similar to rates observed in the
      authors' local cohort (92%). CONCLUSIONS: Cubic splines can be used to generate
      quantitative natural histories for individual patients with ESLD and may be
      useful for developing clinically robust microsimulation models of other diseases.

PMID- 16282214
TI  - Estimation of markov chain transition probabilities and rates from fully and
      partially observed data: uncertainty propagation, evidence synthesis, and model
      calibration.
AB  - Markov transition models are frequently used to model disease progression. The
      authors show how the solution to Kolmogorov's forward equations can be exploited
      to map between transition rates and probabilities from probability data in
      multistate models. They provide a uniform, Bayesian treatment of estimation and
      propagation of uncertainty of transition rates and probabilities when 1)
      observations are available on all transitions and exact time at risk in each
      state (fully observed data) and 2) observations are on initial state and final
      state after a fixed interval of time but not on the sequence of transitions
      (partially observed data). The authors show how underlying transition rates can
      be recovered from partially observed data using Markov chain Monte Carlo methods
      in WinBUGS, and they suggest diagnostics to investigate inconsistencies between
      evidence from different starting states. An illustrative example for a 3-state
      model is given, which shows how the methods extend to more complex Markov models
      using the software WBDiff to compute solutions. Finally, the authors illustrate
      how to statistically combine data from multiple sources, including partially
      observed data at several follow-up times and also how to calibrate a Markov model
      to be consistent with data from one specific study.

PMID- 16282215
TI  - The interpretation of random-effects meta-analysis in decision models.
AB  - This article shows that the interpretation of the random-effects models used in
      meta-analysis to summarize heterogeneous treatment effects can have a marked
      effect on the results from decision models. Sources of variation in meta-analysis
      include the following: random variation in outcome definition (amounting to a
      form of measurement error), variation between the patient groups in different
      trials, variation between protocols, and variation in the way a given protocol is
      implemented. Each of these alternatives leads to a different model for how the
      heterogeneity in the effect sizes previously observed might relate to the effect
      size(s) in a future implementation. Furthermore, these alternative models require
      different computations and, when the net benefits are nonlinear in the efficacy
      parameters, result in different expected net benefits. The authors' analysis
      suggests that the mean treatment effect from a random-effects meta-analysis will
      only seldom be an appropriate representation of the efficacy expected in a future
      implementation. Instead, modelers should consider either the predictive
      distribution of a future treatment effect, or they should assume that the future
      implementation will result in a distribution of treatment effects. A worked
      example, in a probabilistic, Bayesian posterior framework, is used to illustrate
      the alternative computations and to show how parameter uncertainty can be
      combined with variation between individuals and heterogeneity in meta-analysis.

PMID- 16282216
TI  - Willingness to pay per quality-adjusted life year in a study of knee
      osteoarthritis.
AB  - BACKGROUND: Determining whether a particular medical intervention is cost
      effective requires that a threshold of cost per benefit gained be established. As
      debate continues over the appropriate threshold, we present measures of
      willingness to pay (WTP) per quality-adjusted life year (QALY) for own health and
      2 hypothetical osteoarthritis scenarios. METHODS: One hundred ninety-three
      persons, located through random digit dialing in Harris County, Texas, completed
      face-to-face interviews collecting demographic information and health preferences
      using visual analog scale, time tradeoff, standard gamble, and WTP methodologies.
      RESULTS: The mean WTP/QALY for all methods was lower (range, $1221-$5690/QALY)
      than many estimates from revealed preference studies and lower than the oft-cited
      arbitrary cutoff of $50 000. WTP/QALY was highest when participants were judging
      their personal health improvements as opposed to hypothetical scenarios. There
      were some significant differences in WTP/QALY across elicitation methodologies
      for the same scenario. Demographic characteristics were not associated with
      WTP/QALY measures. CONCLUSIONS: The health states and improvements in health
      evaluated here do not contain a risk of mortality, unlike many situations in
      which WTP/QALY has been previously evaluated. The lower WTP/QALY values found
      here may indicate that the presence of a mortality risk reduction substantially
      increases stated WTP/QALY. Appropriate thresholds for cost-effectiveness may be
      dependent on the context of a situation, including risk of mortality.

PMID- 16282217
TI  - Willingness to pay for a quality-adjusted life year: implications for societal
      health care resource allocation.
AB  - BACKGROUND: Health-state preferences can be combined with willingness-to-pay
      (WTP) data to calculate WTP per quality-adjusted life year (QALY). The WTP/QALY
      ratios provide insight into societal valuations of expenditures for medical
      interventions. METHODS: The authors measured preferences for current health in 3
      patient populations (N = 391) using standard gamble, time trade-off, visual
      analog scale, and WTP, then they calculated WTP/QALY ratios. The ratios were
      compared with several proposed cost/QALY cost-effectiveness ratio thresholds, the
      value-of-life literature, and with WTP/QALY ratios derived from published
      preference research. RESULTS: Mean WTP/QALY ratios ranged from 12,500 to 32,200
      US dollars (2003 US dollars). All values were below most published cost
      effectiveness ratio thresholds, below the ratio from a prototypic medical
      treatment covered by Medicare (i.e., renal dialysis), and below ratios from the
      value-of-life literature. The WTP/QALY ratios were similar to those calculated
      from published preference data for patients with symptomatic meno-pause,
      dentofacial deformities, asthma, or dermatologic disorders. CONCLUSIONS: WTP/QALY
      ratios calculated using preference data collected from diverse populations are
      lower than most proposed thresholds for determining what is "cost-effective."
      Current proposed cost-effectiveness ratio thresholds may overestimate the
      willingness of society to pay for medical interventions.

PMID- 16282218
TI  - Local applicability of clinical and model-based probability estimates.

PMID- 16282220
TI  - Interactions between the Mas-related receptors MrgD and MrgE alter signalling and
      trafficking of MrgD.
AB  - When expressed via an inducible promoter in human embryonic kidney 293 cells, the
      rat Mas-related gene D (rMrgD) receptor responded to beta-alanine but not L
      alanine by elevating intracellular [Ca(2+)], stimulating phosphorylation of the
      mitogenactivated protein kinases known as extracellular signal-regulated kinase
      (ERK) 1 and ERK2 and translocating from the plasma membrane to punctate
      intracellular vesicles. By contrast, the related rat Mas-related gene E (rMrgE)
      receptor did not respond to beta-alanine. Coexpression of rMrgD with rMrgE, which
      occurs in peripheral nociceptive neurons, allowed coimmunoprecipitation of the
      two receptors and resulted in the detection of cell surface rMrgD-rMrgE
      heterodimers via timeresolved fluorescence resonance energy transfer. These
      interactions increased the potency of beta-alanine to phosphorylate ERK1 and ERK2
      as well as maintaining the capacity of beta-alanine to elevate intracellular
      [Ca(2+)], which was reduced in magnitude and slowed in response with increasing
      times of expression of rMrgD in isolation. Associated with these effects, the
      presence of rMrgE restricted beta-alanine-induced internalization of rMrgD. This
      is the first report of heterodimeric interactions between members of the Mas
      related gene (Mrg) receptor family and indicates that interactions between rMrgD
      and rMrgE modulate the function of rMrgD. Because the Mrg receptors are potential
      therapeutic targets in pain, these results suggest that efforts to understand the
      function and regulation of individual Mrg family receptors may require
      coexpression of relevant pairs.

PMID- 16282221
TI  - The cannabinoid CB1 receptor antagonist rimonabant (SR141716) inhibits cell
      proliferation and increases markers of adipocyte maturation in cultured mouse 3T3
      F442A preadipocytes.
AB  - Adipocyte cell proliferation is an important process in body fat mass development
      in obesity. Adiponectin or Acrp30 is an adipocytokine exclusively expressed and
      secreted by adipose tissue that regulates lipid and glucose metabolism and plays
      a key role in body weight regulation and homeostasis. Adiponectin mRNA expression
      in adipose tissue and plasma level of adiponectin are decreased in obesity and
      type 2 diabetes. In obese rodents, the selective CB(1) receptor antagonist
      rimonabant reduces food intake and body weight and improves lipid and glucose
      parameters. We have reported previously that rimonabant stimulated adiponectin
      mRNA expression in adipose tissue of obese fa/fa rats, by a direct effect on
      adipocytes. We report here that rimonabant (10-400 nM) inhibits cell
      proliferation of cultured mouse 3T3 F442A preadipocytes in a concentration
      dependent manner. In parallel to this inhibitory effect on preadipocyte cell
      proliferation, rimonabant (25-100 nM) stimulates mRNA expression and protein
      levels of two late markers of adipocyte differentiation (adiponectin and
      glyceraldehyde-3-phosphate dehydrogenase) with a maximal effect at 100 nM,
      without inducing the accumulation of lipid droplets. Furthermore, treatment of
      mouse 3T3 F442A preadipocytes with rimonabant (100 nM) inhibits basal and serum
      induced p42/44 mitogen-activated protein (MAP) kinase activity. These results
      suggest that inhibition of MAP kinase activity by rimonabant may be one of
      mechanisms involved in the inhibition of 3T3 F442A preadipocyte cell
      proliferation and stimulation of adiponectin and GAPDH expression. The inhibition
      of preadipocyte cell proliferation and the induction of adipocyte late
      "maturation" may participate in rimonabant-induced antiobesity effects,
      particularly the reduction of body fat mass.

PMID- 16282223
TI  - The AWHONN Near-Term Infant Initiative: a conceptual framework for optimizing
      health for near-term infants.
AB  - In June 2005, the Association of Women's Health, Obstetric and Neonatal Nurses
      launched a multiyear initiative to address the unique physiologic and
      developmental needs of near-term infants (NTIs) defined as those born between 34
      and 37 weeks post-menstrual age. The Optimizing Care for the Near-Term Infant
      Conceptual Model integrates the concepts of neonatal physiologic functional
      status, nursing care practices, care environment, and the essential role of the
      family both in the hospital and beyond. The elements of the model will serve to
      guide program and resource development within the Near-Term Infant Initiative.
      Goals of the initiative are to raise awareness of the NTI population's unique
      needs, emphasize the need for research, encourage development and adoption of
      evidence-based guidelines to promote safe care, and provide resources that assist
      nurses and other health care professionals in risk-based assessment of NTIs.

PMID- 16282224
TI  - Application of the social ecological model in folic acid public health
      initiatives.
AB  - All women of childbearing age who are capable of becoming pregnant should consume
      0.4 mg/400 microg of folic acid daily. Folic acid decreases the incidence of
      neural tube defects in newborns. Despite continued public health initiatives,
      many women still do not consume the recommended daily requirement. This article
      analyzes the use of the social ecological model in folic acid public health
      initiatives and emphasizes assessing the outcomes of such initiatives.

PMID- 16282225
TI  - Coming to the cultural "in-between": nursing insights from a Hmong birth case
      study.
AB  - This article discusses the historical background and traditional beliefs of the
      Hmong. Cultural conflict occurs when traditional Hmong beliefs and Western health
      care ideologies are misunderstood. A specific case study focuses on care of a
      Hmong woman and her husband after a precipitous birth, hemorrhage, and surgical
      intervention. Nursing insights are identified from "in-between" the cultures.
      Establishing cultural awareness is an essential first step toward cultural
      competence.

PMID- 16282226
TI  - Heart rate variability responses of a preterm infant to kangaroo care.
AB  - OBJECTIVE: To examine the effect of kangaroo care on heart rate variability in a
      healthy preterm infant. DESIGN: Case study. SETTING: Private room on a postpartum
      unit. PARTICIPANT: A mother-preterm infant dyad. INTERVENTION: Kangaroo (skin-to
      skin) care. MAIN OUTCOME MEASURE: Heart rate variability, a noninvasive
      measurement of the sympathetic and parasympathetic components of the autonomic
      nervous system's influence on heart rate. RESULTS: Heart rate variability,
      especially the parasympathetic component, was high when the infant was fussy in
      the open crib, indicating increased autonomic nervous system activity. With
      kangaroo care, the infant fell asleep, and both sympathetic and parasympathetic
      components of heart rate variability decreased. CONCLUSIONS: The wide
      fluctuations in the parasympathetic component of heart rate variability suggest
      immaturity of the sympathovagal response. Overall, kangaroo care produced changes
      in heart rate variability that illustrate decreasing stress.

PMID- 16282227
TI  - Provider support of spontaneous pushing during the second stage of labor.
AB  - OBJECTIVE: To describe the association between provider communication and actual
      maternal pushing behavior in second-stage labor and to test differences in length
      of second stage and total maternal pushing time by maternal pushing behavior.
      DESIGN: Descriptive. SETTING: Midwest hospital birth unit. PARTICIPANTS: Twenty
      primigravidas who gave birth vaginally. INTERVENTION: Type of provider
      communication (supportive of spontaneous or directed pushing). MAIN OUTCOME
      MEASURE: Maternal pushing behavior (spontaneous or directed) documented by
      videotape review. RESULTS: The percentage of provider communication supporting
      spontaneous pushing versus directed pushing and the percentage of actual
      spontaneous versus directed maternal pushing behavior were associated (Pearson r
      = .80, p = .001, for spontaneous and r = .89, p = .001, for directed). Neither
      duration of second stage (t = .06, p = .95) nor time spent pushing (t = .15, p =
      .89) differed by spontaneous versus directed pushing style. CONCLUSION: The
      proportion of spontaneous pushing by the birthing woman was positively and
      significantly associated with the proportion of caregiver communication
      supporting and encouraging spontaneous pushing. Importantly, spontaneous pushing
      did not significantly lengthen the duration of second-stage labor or total time
      spent pushing.

PMID- 16282228
TI  - The importance of providing smoking relapse counseling during the postpartum
      hospitalization.
AB  - OBJECTIVES: To determine during the postpartum period (a) the most feasible time
      for addressing smoking relapse, (b) the reasons women relapse, (c) differences in
      relapse rates in women who receive a counseling intervention in the immediate
      postpartum period compared to those who do not, and (d) differences in self
      reporting of tobacco use compared to cotinine analysis. DESIGN: Randomized
      clinical trial. SETTING: Medical center in the Northeast United States and two
      prenatal care sites. PARTICIPANTS: A nonprobability convenience sample of 62
      pregnant women. INTERVENTION: A brief counseling session using empowerment
      techniques, motivational interviewing, identification of stressors and individual
      coping strategies, and educational materials. MAIN OUTCOMES MEASURE: Relapse to
      smoking measured by cotinine analysis and descriptive data collected during the
      antepartum, intrapartum, and postpartum periods. RESULTS: Fifty-two percent of
      women relapsed to smoking by the 2nd week postdelivery, identifying rest and
      relaxation and depression as main factors for relapsing. Chi-square analysis
      showed no significant difference between the two groups regarding the
      intervention provided. There was a 39% discrepancy rate between self-reporting of
      tobacco use and cotinine analysis during pregnancy and a 27% discrepancy rate
      after delivery. CONCLUSIONS: Because of the high occurrence of relapse in the
      first 2 weeks after delivery, it is imperative that nurses provide interventions
      to women before their postpartum hospital discharge to prevent smoking relapse.
      Nurses should also address smoking behaviors each trimester because women stopped
      smoking at different time intervals and self-reported data were unreliable.

PMID- 16282229
TI  - Use of a pregnancy support web site by low-income African American women.
AB  - OBJECTIVE: To examine the feasibility and usage pattern of a social support Web
      site by low-income pregnant African American women. DESIGN: Descriptive. SETTING:
      Homes of participants. PARTICIPANTS: Nineteen pregnant African American women who
      were pregnant for the first time, were low risk, and attending a prenatal clinic.
      INTERVENTION: Culturally congruent Web site providing information on pregnancy
      related health behaviors and other pregnancy issues. MAIN OUTCOME MEASURES:
      Number of visits to Web site, most popular pages, content analysis of postings,
      and e-mails to a nurse. RESULTS: Participants were able to learn to use the Web
      site easily. They accessed the discussion board the most frequently, followed by
      changes during pregnancy by month, ask-a-nurse feature, ultrasound, stories about
      pregnant women, and spirituality. CONCLUSIONS: The discussion board is the most
      effective way to deliver informational social support on a comprehensive social
      support Web site.

PMID- 16282230
TI  - Relationships between physical abuse during pregnancy and risk factors for
      preterm birth among women in Manitoba.
AB  - OBJECTIVE: To describe the prevalence and correlates of physical abuse during the
      year of pregnancy and to explore the association between physical abuse and other
      risk factors for preterm birth. DESIGN: Secondary analysis of data from a case
      control study of risk factors for preterm birth. SETTING: Two tertiary care
      hospitals in the Canadian province of Manitoba. PARTICIPANTS: Six hundred eighty
      postpartum women who delivered a live singleton newborn after spontaneous onset
      of labor. MAIN OUTCOME MEASURES: Instruments included the Abuse Assessment
      Screen, Prenatal Psychosocial Profile, Perceived Stress Scale, and a
      questionnaire to collect data on demographic characteristics, complications
      during pregnancy, and lifestyle behaviors. RESULTS: Sixty-four women (9.4%)
      reported being physically abused during the year of pregnancy. Abused women were
      significantly more likely to be younger, single, of lower income, and less
      educated than nonabused women. Significant correlates of abuse, after adjusting
      for other factors in a logistic regression, included the following: illicit drug
      use, low support from partner, moving two or more times in the past year, high
      life event stress, bladder infection during pregnancy, Aboriginal race/ethnicity,
      and single marital status. CONCLUSION: This study suggests that physical abuse
      during pregnancy is associated with other risk factors for preterm birth,
      particularly stress and behavioral risk factors such as substance abuse.

PMID- 16282231
TI  - The lived experience of pregnancy while carrying a child with a known, nonlethal
      congenital abnormality.
AB  - OBJECTIVE: To gain an understanding of the experience of pregnancy while carrying
      a child with a known, nonlethal congenital abnormality. DESIGN: Phenomenological
      study. SETTING: The participants were interviewed in their own homes, a quiet
      clinic room, or another location comfortable for them. PARTICIPANTS: Fifteen
      pregnant women carrying a child with a nonlethal, congenital abnormality
      participated. RESULTS: The pregnancy experience was of a paradoxical nature.
      Knowledge of the fetal diagnosis resulted in both positive and negative
      consequences. Three major themes were common to the experience for women: Time is
      good, but it is also the enemy; you grieve, but you do not grieve; my baby's not
      perfect, but (s)he's still mine. CONCLUSION: Because of the paradoxical feelings
      experienced, women need as much information as they request regarding the
      abnormality, its treatment, and prognosis. An appointment during pregnancy with
      pediatric specialists to discuss the plan for care of the infant after delivery
      is beneficial. Health care providers should support women's prenatal attachment
      during this unique pregnancy.

PMID- 16282232
TI  - Effect of less frequent bathing on premature infant skin.
AB  - OBJECTIVE: To evaluate the effect of less frequent bathing on skin flora of
      premature infants. DESIGN: Randomized clinical trial comparing the impact of
      every other day bathing to every 4th day bathing on skin flora type and colony
      count. SETTING: University of California, San Francisco, Medical Center Level IV
      neonatal intensive-care unit. PARTICIPANTS: Fifty-three premature infants less
      than 37 weeks gestational age, 14 days or older, and receiving a bath.
      INTERVENTION: Premature infants were randomized to either every other day bathing
      (control group, n = 28) or every 4th day bathing (intervention group, n = 25).
      MAIN OUTCOME MEASURE: Skin flora type and colony count obtained weekly. RESULTS:
      Repeated-measures ANOVA was used to test the main effect of group, time, and
      Group x Time interaction. These factors were not statistically significant; group
      F(1,21) = 1.842, p = .189; time F(3,63) = 1.359, p = .263; Group x Time
      interaction F(3,63) = 0.753, p = .525. None of the infants developed an infection
      as a result of participating in the study protocol. CONCLUSION: Every 4th day
      bathing of premature infants appears to be safe.

PMID- 16282234
TI  - Social support in Mexican American childbearing women.
AB  - Because the Mexican American population in the United States is increasing,
      nurses will inevitably come into contact with members of this cultural group.
      Social support is essential for women to adapt to the demands of the perinatal
      period, and Mexican American childbearing women face particular challenges in
      obtaining social support. In this article, traditional roles and social support
      in Mexican American families are described, the challenges of delivering prenatal
      care within these traditions are discussed, and strategies for nursing
      intervention are offered.

PMID- 16282235
TI  - Social support in postpartum adolescents: guidelines for nursing assessments and
      interventions.
AB  - Social support plays an important role in reducing stress for postpartum
      adolescents. Health care providers should assess social support of postpartum
      adolescents each time they encounter the health care system. The assessment
      should include culturally sensitive individual questions or established social
      support instruments. If social support is found to be inadequate or insufficient,
      professional support interventions may be indicated. Health professionals should
      use clinical pathways to guide assessments and professional support interventions
      with postpartum adolescents.

PMID- 16282236
TI  - Strengthening social support for the low-income mother: five critical questions
      and a guide for intervention.
AB  - The visit to the nurse can become a vehicle for low-income mothers to develop one
      of the most critical health resources available to them: social support. Economic
      limitations require low-income mothers to create social support structures that
      are functional but may not match notions of ideal social support. Extensive
      experience of two advanced practice psychiatric mental health nurse-clinicians
      revealed that low-income mothers' social support was characterized by concern for
      basic necessities, precarious situations, self-replicating patterns,
      entrepreneurial requirements, and demonstrations of strengths. Five key questions
      during the encounter between nurse and mother can assist the nurse in planning
      interventions that fit these mothers' needs and benefit their health and that of
      their children.

PMID- 16282237
TI  - Influence of maternal bone lead burden and calcium intake on levels of lead in
      breast milk over the course of lactation.
AB  - The authors studied 367 women who were breastfeeding their infants in Mexico
      City, Mexico, between 1994 and 1995 to evaluate the effect of cumulative lead
      exposure, breastfeeding practices, and calcium intake on breast milk lead levels
      over the course of lactation. Maternal blood and breast milk lead levels were
      measured at 1, 4, and 7 months postpartum. Bone lead measurements were obtained
      at 1 month postpartum. At 1, 4, and 7 months postpartum, respectively, the mean
      breast milk lead levels were 1.4 (standard deviation (SD), 1.1), 1.2 (SD, 1.0),
      and 0.9 (SD, 0.8) microg/liter and showed a significant decreasing trend over the
      course of lactation (p < 0.00001). The relations of bone lead and blood lead to
      breast milk lead were modified by breastfeeding practice, with the highest breast
      milk lead levels among women with a high level of patella lead who were
      exclusively breastfeeding. Dietary calcium supplementation increased the rate of
      decline in breast milk lead by 5-10%, in comparison with a placebo, over the
      course of lactation, suggesting that calcium supplementation may constitute an
      important intervention strategy, albeit with a modest effect, for reducing lead
      in breast milk and thus the potential for exposure by infants.

PMID- 16282238
TI  - Estimated effects of disinfection by-products on birth weight in a population
      served by a single water utility.
AB  - Research has suggested that trihalomethane exposures during pregnancy might
      impair fetal growth. Most epidemiologic studies, however, relied on relatively
      crude exposure assessment methods and did not examine racial/ethnic subgroups.
      During 1999-2001, vital records data were obtained for a large, racially diverse
      population residing in 27 Massachusetts communities that received drinking water
      from a single public utility. The water system was monitored weekly for
      trihalomethanes and, system-wide, it maintained geographically stable total
      trihalomethane levels during the study period. The authors examined the effects
      of trimester-specific and pregnancy average exposures to total trihalomethane in
      drinking water on term low birth weight in all singleton births. A high average
      total trihalomethane exposure (> or = 70 microg/liter) during the second
      trimester increased the risk of term low birth weight (odds ratio = 1.50, 95%
      confidence interval (CI): 1.07, 2.10). The estimated risk increase for Caucasians
      during the second trimester was 37% (95% CI: 0.80, 2.36), while for all minority
      women combined (i.e., African Americans, Hispanics, and Asians) it was 60% (95%
      CI: 1.03, 2.47). The study data suggest that high levels (> or = 70 microg/liter)
      of trihalomethanes experienced during the second trimester and pregnancy overall
      may affect fetal growth.

PMID- 16282239
TI  - Re: "Body mass index and incident ischemic heart disease in South Korean men".

PMID- 16282240
TI  - Trends in the incidence rates of nasopharyngeal carcinoma among Chinese Americans
      living in Los Angeles County and the San Francisco metropolitan area, 1992-2002.
AB  - Nasopharyngeal carcinoma is much more common in Asian countries than in Western
      countries. However, since the 1980s, nasopharyngeal carcinoma incidence has
      fallen among both men and women in Hong Kong, and recently a similar trend has
      also been noted in Singapore. Using data from the Surveillance, Epidemiology, and
      End Results Program and the US Census, the authors evaluated recent trends in the
      incidence rates of nasopharyngeal carcinoma among Chinese living in Los Angeles
      County and in the San Francisco-Oakland (California) metropolitan area. From 1992
      to 2002, the rates of nasopharyngeal carcinoma in these two populations decreased
      in men by 37% (95% confidence interval: -54, -12) but in women by just 1% (95%
      confidence interval: -40, 64). In Chinese men, the overall decline in incidence
      was limited primarily to a decline in the rate of type I tumors (differentiated
      squamous tumors with keratin production). While the reasons underlying the
      observed patterns of incidence remain to be determined, changes in lifestyle and
      environment are likely to be contributory factors.

PMID- 16282241
TI  - Re: "Sibship characteristics and risk of allergic rhinitis and asthma".

PMID- 16282242
TI  - Metachronous gastric MALT lymphoma and early gastric cancer.

PMID- 16282243
TI  - Risk factors for venous thromboembolic events in cancer patients.
AB  - BACKGROUND: Cancer patients of the Department of Internal Medicine (Cancer
      Research) of the Essen University Medical School (Tumor Clinics), Germany, were
      examined and questioned with the aim of identifying those who run a high risk of
      deep vein thrombosis (DVT). PATIENTS AND METHODS: Between September 2002 and
      April 2003, cancer therapy and DVT risk factors of 507 cancer patients (53%
      males, 47% females, mean age 56+/-12 years) were documented. During a mean follow
      up of 8+/-5 months, 60 patients (12%) suffered from new venous thromboembolic
      events (VTE): 28 at the lower limb, 25 at the upper limb and 13 pulmonary
      embolisms. RESULTS: The following factors were considered as predictive for an
      increased VTE risk: inpatient treatment (P<0.0001), prior DVT in medical history
      (P=0.0275), DVT in family (P=0.0598), chemotherapy (P=0.0080), fever (P=0.0093)
      and CRP (P<0.001). After combining factors in one variable (number of factors)
      the predicted VTE risk increased with the number of factors in both outpatients
      (OR 1.85, 95% CI 1.18-2.88, P=0.0071) and inpatients (OR 2.34, 95% CI 1.63-3.36,
      P<or=0.0001). In the absence of all these factors the predicted VTE risk was
      2.3%, increasing to 72% if all were present. CONCLUSIONS: In cancer patients the
      risk of VTE steadily increases with the number of risk factors, and
      identification of patients at high risk is possible.

PMID- 16282244
TI  - Recombinant human angiostatin (rhAngiostatin) in combination with paclitaxel and
      carboplatin in patients with advanced non-small-cell lung cancer: a phase II
      study from Indiana University.
AB  - BACKGROUND: Recombinant human angiostatin (rhAngiostatin) functions as a potent
      inhibitor of angiogenesis. This study combined rhAngiostatin with a standard
      chemotherapy regimen in patients with advanced non-small-cell lung cancer
      (NSCLC). PATIENTS AND METHODS: Eligible patients had chemotherapy-naive stage
      IIIB (with pleural effusion) or IV NSCLC, performance status (PS) 0 or 1, no
      history of bleeding, brain metastasis or requirements for anti-coagulation.
      Patients received carboplatin (AUC 5) intravenously and paclitaxel (175 mg/m2)
      intravenously day 1 + subcutaneous rhAngiostatin at either 15 mg or 60 mg twice
      daily. Cycles were repeated every 3 weeks, for up to six cycles. Patients without
      progression after completing at least four cycles were continued on maintenance
      rhAngiostatin until disease progression. RESULTS: Patient characteristics (n =
      24) were: 16 males, median age 66 years (range 45-78), 54% PS 1, 83.3% stage IV
      and 62.5% adenocarcinoma. Grade 3/4 toxicities included: fatigue 47.8%,
      neutropenia 39.1%, dyspnea 39.1%, vascular 26.1% and infection 17.4%. The overall
      response rate was 39.1%, 39.1% stable disease and 21.7% progressive disease.
      Median time to progression was 144 days, and 1-year survival was 45.8%.
      CONCLUSIONS: rhAngiostatin in combination with paclitaxel and carboplatin is
      feasible and results in a high disease control rate in patients with advanced
      NSCLC.

PMID- 16282245
TI  - Hypersensitivity reactions to oxaliplatin: experience in a single institute.
AB  - BACKGROUND: A rising incidence of hypersensitivity reactions to oxaliplatin has
      been observed as a result of increasing clinical use. Epidemiological and
      clinical features of these reactions are reviewed. PATIENTS AND METHODS: Records
      of patients treated with a modified FOLFOX regimen from March 1999 to March 2004
      were reviewed. RESULTS: One hundred and eighty patients were identified. Twenty
      seven patients (15%) have been labelled as allergic to oxaliplatin, the
      proportion being higher among those receiving oxaliplatin in palliative second
      line or above settings (19.6%) than in adjuvant or palliative first-line settings
      (10.2%). Some 2.2% of them developed grade 3-4 reactions. The reactions occurred
      after a mean (+/-SD) of 8.5 (+/-4.2) cycles (range 1-18). Among the 14 patients
      re-exposed to oxaliplatin, four (28.6%) developed hypersensitivity reaction, in
      two of whom (14.3%) reactions were grade 3-4 in severity. CONCLUSIONS: The risk
      of developing hypersensitivity reactions in patients receiving oxaliplatin should
      not be underestimated. The risk of developing potentially life-threatening
      hypersensitivity reactions should be explained to patients in the context of the
      potential benefits of such therapy. Patients receiving oxaliplatin infusion
      should be closely monitored. Once a patient develops hypersensitivity reaction to
      oxaliplatin, re-exposure should only be considered if the reaction is mild and
      there has been documented clinical benefit from previous doses of this agent.

PMID- 16282246
TI  - Capecitabine in combination with preoperative radiation therapy in locally
      advanced, resectable, rectal cancer: a multicentric phase II study.
AB  - BACKGROUND: The aim of the study was to evaluate tolerance and efficacy of
      preoperative treatment with capecitabine in combination with radiation therapy
      (RT) in patients with locally advanced, resectable, rectal cancer. PATIENTS AND
      METHODS: Fifty-three patients with potentially resectable T3, N0-2 (87%) and T4,
      N0-2 (13%) rectal cancer were treated with capecitabine (825 mg/m2, twice daily
      for 7 days/week) and concomitant RT (50.4 Gy/28 fractions). Patients underwent
      surgery after 6-8 weeks followed, upon physician's indications, by 4-months
      adjuvant capecitabine. The primary end point was to determine the rate of
      pathologic complete response. Secondary end points were to assess the rate of
      clinical response and the safety profile. RESULTS: All patients but two completed
      the RT programme and 47 (89%) received 81%-100% of the capecitabine dose (100% of
      dose in 72% patients, 81%-95% in 17% patients and 48%-74% in 11% of patients). No
      patient had grade 4 toxicity. Grade 3 toxicity occurred in six patients (11%) and
      consisted mainly of leucopenia (4%) and hand-foot syndrome (4%). Mild or moderate
      toxicity was common and included leucopenia (72%), diarrhea (40%), proctitis
      (34%) and skin toxicity (20%). The overall clinical response rate was 58% and the
      downstaging rate was 57%, with a pathologic complete response rate of 24%. Among
      34 patients with low-lying tumors (<or=5 cm from anal verge), 20 (59%) had a
      sphincter-saving operation. CONCLUSIONS: Preoperative chemoradiation with
      capecitabine and RT appeared to be effective in locally advanced resectable,
      rectal cancer. The favorable safety profile of the combination might warrant the
      use of capecitabine and RT with other effective new drugs.

PMID- 16282247
TI  - Influence of thyroid hormone receptors on breast cancer cell proliferation.
AB  - BACKGROUND: The involvement of thyroid hormones in the development and
      differentiation of normal breast tissue has been established. However, the
      association between breast cancer and these hormones is controversial. Therefore,
      the objective of the present study was to determine the protein expression
      pattern of thyroid hormone receptors in different human breast pathologies and to
      evaluate their possible relationship with cellular proliferation. PATIENTS AND
      METHODS: The presence of thyroid hormone receptors was evaluated by
      immunohistochemistry and western blot analysis in 84 breast samples that included
      12 cases of benign proliferative diseases, 20 carcinomas in situ and 52
      infiltrative carcinomas. RESULTS: TR-alpha was detected in the nuclei of
      epithelial cells from normal breast ducts and acini, while in any pathological
      type this receptor was located in the cytoplasm. However, TR-beta presented a
      nuclear location in benign proliferative diseases and carcinomas in situ and a
      cytoplasmatic location in normal breast and infiltrative carcinomas. The highest
      proliferation index was observed in carcinomas in situ, although in infiltrative
      carcinomas an inverse correlation between this index and the TR-alpha expression
      was encountered. CONCLUSIONS: The results of this study reveal substantial
      changes in the expression profile of thyroid hormone receptors suggesting a
      possible deregulation that could trigger breast cancer development.

PMID- 16282248
TI  - Pegylated liposomal doxorubicin and carboplatin in advanced gynecologic tumors: a
      prospective phase I/II study of the Arbeitsgemeinschaft Gynaekologische Onkologie
      Studiengruppe Ovarialkarzinom (AGO-OVAR).
AB  - BACKGROUND: Single-agent platinum and single-agent pegylated liposomal
      doxorubicin (PLD) are both effective in the treatment of gynecologic
      malignancies. Based on evidence that combination platinum-containing regimens
      offer superior efficacy versus single-agent regimens, we conducted this study to
      determine the maximum tolerated dose (MTD) of PLD in combination with
      carboplatin. PATIENTS AND METHODS: In this phase I/II dose-finding study, six
      courses of PLD (20, 30, 40 or 50 mg/m2) and carboplatin (AUC 6) were administered
      every 28 days to women with advanced gynecologic malignancies. Three to six
      patients were treated at each dose level; an additional 12 patients were treated
      at the MTD. RESULTS: PLD 40 mg/m2 was identified as the MTD when administered
      with carboplatin. Five of 18 patients experienced a dose-limiting toxicity at the
      MTD; two patients had grade 3/4 neutropenia, and one each had grade 3 emesis and
      grade 3 thrombocytopenia and thrombosis. No patient developed cardiotoxicity. In
      11 patients evaluable for response, there were two complete responses, two
      partial responses and four patients with stable disease. CONCLUSIONS: The MTD for
      PLD when administered in combination with carboplatin is 40 mg/m2. This regimen
      is well tolerated and offers promising activity in women with advanced
      gynecologic malignancies.

PMID- 16282249
TI  - Is high-dose chemotherapy based on carboplatin, a late dose-intensification of a
      cisplatin-based salvage chemotherapy in germ cell tumour patients?

PMID- 16282250
TI  - Minding my own business.

PMID- 16282251
TI  - Economic grand rounds: incentives for primary care providers to participate in a
      collaborative care program for depression.

PMID- 16282252
TI  - Practical geriatrics: depression, cognition, and anxiety among postmenopausal
      women with breast cancer.

PMID- 16282253
TI  - Datapoints: medicaid as a payer for services provided by psychiatrists.

PMID- 16282254
TI  - Use of mental health services after hurricane Floyd in North Carolina.
AB  - OBJECTIVE: The aim of this study was to examine the impact of a natural disaster,
      Hurricane Floyd, on the use of mental health services in a Medicaid population in
      North Carolina. METHODS: Difference-in-differences techniques were used to
      determine month-by-month and 12-month postevent average effects of the hurricane
      on the use of mental health services at the county level. The exposure group was
      drawn from 14 severely affected counties, and the control group was drawn from 56
      unaffected counties. Data were analyzed from July 1998 (14 months before the
      hurricane) to September 2000 (12 months after the hurricane). RESULTS: The number
      of per-enrollee per-month outpatient visits to psychologists or licensed clinical
      social workers and the number of outpatient visits to non-mental health
      specialists showed a statistically significant increase over the 12-month
      postevent period, whereas the number of inpatient admissions for behavioral
      health reasons decreased. Dollars spent on antianxiety medication per enrollee
      per month showed a statistically significant decrease. CONCLUSIONS: The aftermath
      of Hurricane Floyd was associated with significantly greater use of mental health
      services in the Medicaid community in North Carolina for a few services. However,
      it is unclear whether changes in utilization patterns were due to the greater
      demand for services or to the availability of other services that may have served
      as substitutes. The results of this study underscore the importance of planning
      for service implementation and delivery after similar events in other states.

PMID- 16282255
TI  - Follow-up of Pentagon employees two years after the terrorist attack of September
      11, 2001.
AB  - OBJECTIVE: This study examined probable posttraumatic stress disorder (PTSD) and
      probable depression, degree of psychological distress, and rates of mental health
      treatment in a sample of Pentagon staff two years after the terrorist attack of
      September 11, 2001. METHODS: Anonymous surveys were administered to staff at one
      Pentagon work center. Respondents were asked about exposure to the attack;
      injuries; exposure to dead bodies or families of the deceased; psychological
      distress; and use of mental health services. Probable PTSD and depression were
      assessed with the PCL-17 and the PHQ-9. RESULTS: A total of 267 responses were
      received. Fourteen percent of the sample had probable PTSD, and 7 percent had
      probable depression. Staff who were at the Pentagon on the day of the attack were
      more likely to have probable PTSD and probable depression. Exposure through
      watching television was not associated with a higher frequency of probable PTSD,
      probable depression, or distress. Injury during the attack was associated with a
      higher frequency of probable PTSD, probable depression, and distress. Respondents
      who were exposed to dead bodies or who acted as lay counselors to families of the
      deceased were more likely to have probable PTSD and depression and to report
      chronic distress. Of those with probable PTSD, 70 percent made at least one
      mental health visit during the next two years. Of those with probable depression,
      74 percent reported at least one mental health visit. CONCLUSIONS: Direct
      exposure to the September 11 terrorist attack on the Pentagon, injury during the
      attack, and exposure to dead bodies or acting as a lay counselor to families of
      persons who were killed during the attack were all associated with higher
      frequencies of probable psychiatric illness and higher levels of psychological
      distress two years after the attack. Among survivors who had probable psychiatric
      illness, more than two-thirds received mental health treatment after the attack.

PMID- 16282256
TI  - A randomized trial of short-term acute residential treatment for veterans.
AB  - OBJECTIVE: A variety of alternatives to acute psychiatric hospital care have been
      developed over the past several decades. including San Diego's short-term acute
      residential treatment (START) program, now comprising a certified and accredited
      network of six facilities with a total of 75 beds. This study compared outcomes,
      patient satisfaction, and episode costs for a sample of 99 veterans who received
      acute care either at an inpatient unit at a Department of Veterans Affairs (VA)
      hospital or at a START facility. METHODS: Consenting participants were randomly
      assigned to one of the two treatment settings. Follow-up was conducted at two
      months. During the follow-up period, participants received treatment as usual.
      Multiple standardized measures were used to maximize validity in assessing
      symptoms, functioning, and quality of life. RESULTS: Participants who were
      treated in either a hospital or the START program showed significant improvement
      between admission, discharge, and two-month follow-up, with few statistically
      significant differences between the groups in symptoms and functioning. There was
      some evidence that START participants had greater satisfaction with services.
      Mean costs for the index episode were significantly lower for START participants
      (65 percent lower) than for those who were treated in the hospital. CONCLUSIONS:
      The results of this study suggest that the START model provides effective
      voluntary acute psychiatric care in a non-hospital-based setting at considerably
      lower cost. Efforts to replicate and evaluate the model at additional locations
      merit attention.

PMID- 16282257
TI  - Community tenure of people with serious mental illness in assertive community
      treatment in Canada.
AB  - OBJECTIVE: This study followed consumers after admission to an assertive
      community treatment program to determine when the first hospital admission was
      more likely to occur, which variables predicted community tenure, and, more
      specifically, whether the availability of within-program hospital beds predicted
      community tenure. METHODS: Data were gathered from three assertive community
      treatment programs in southeastern Ontario--the psychosocial rehabilitation
      program, the community integration program, and the assertive community treatment
      team program. Only the psychosocial rehabilitation program provided within
      program beds. Hospital records of consumers who entered a program between July 1,
      1990, and December 1, 1999, were examined prospectively until January 1, 2000, in
      order to record time to the first admission. Survival analysis based on the life
      tables method was used to estimate the probability of remaining out of the
      hospital at 90-day intervals. Factors associated with time to admission were
      identified by using the Cox proportional hazards model. RESULTS: A total of 333
      consumers were followed: 117 consumers in the psychosocial rehabilitation
      program, 105 in the community integration program, and 111 in the assertive
      community treatment team program. Findings indicated that consumers were most
      likely to be admitted to a hospital in the nine months after entering an
      assertive community treatment program. A diagnosis of substance use disorder,
      higher past hospital use, and the availability of within-program beds were
      associated with an increased risk of admission. CONCLUSIONS: Studies have shown
      that hospitalization remains a reality for many consumers and therefore warrants
      further study. The survival model proved advantageous by allowing a more complete
      and comparable description of consumers' hospitalization patterns that cannot be
      achieved with previously used methods, and it offered the power of regression
      analysis.

PMID- 16282258
TI  - Prevalence of psychiatric disorders and costs of care among adult enrollees in a
      Medicaid HMO.
AB  - OBJECTIVE: Little is known about how psychiatric disorders affect health care
      costs in Medicaid programs. The prevalence of psychiatric disorders and costs of
      care for members of a Medicaid health maintenance organization (HMO) who had
      psychiatric disorders were examined. METHODS: A cross-sectional, observational
      analysis of adult Medicaid beneficiaries over a 12-month period was conducted by
      using data from a health plan that has both an HMO and a behavioral health carve
      out. Claims data were analyzed for 6,500 adults who were eligible for services in
      both plans and who received medical or behavioral health services during calendar
      year 2000. RESULTS: Thirty-nine percent of the 6,500 adults had a psychiatric
      diagnosis. Of this subset, 67.2 percent had received no specialty mental health
      care in the previous year. The presence of any psychiatric diagnosis
      significantly increased total health care costs by a factor of 2.24 ($6,995
      compared with $3,121 for persons with no psychiatric diagnosis) and costs to the
      medical plan by a factor of 1.77 ($4,690 compared with $2,649). For beneficiaries
      with bipolar or psychotic diagnoses, higher health plan costs were due
      predominately to increases in pharmacy and specialty mental health costs. In
      contrast, higher costs for beneficiaries with depression, anxiety, or substance
      use diagnoses were attributable to greater use of general medical services.
      CONCLUSIONS: An analysis of claims data showed that adult Medicaid beneficiaries
      have exceptionally high rates of comorbid psychiatric conditions, which were
      associated with significantly higher medical and pharmaceutical costs. The high
      cost of these beneficiaries to the medical plan has policy implications in terms
      of the importance of addressing mental health issues in Medicaid general medical
      populations.

PMID- 16282259
TI  - Medication treatment patterns for adults with schizophrenia in Medicaid managed
      care in Colorado.
AB  - OBJECTIVE: This study investigated the impact of Colorado's Medicaid mental
      health managed care program on patterns of antipsychotic medication treatment
      among persons with a diagnosis of schizophrenia. These patterns were compared
      with patterns of psychosocial treatment and a measure of symptom change. METHODS:
      Changes in study measures over time in two areas of the state where the policy
      intervention was implemented were compared with changes in measures in areas
      where it was not implemented. The study sample consisted of 235 consumers.
      Measures of antipsychotic medication treatment included any use in a given
      period, months in which a prescription was filled, and use of second-generation
      antipsychotics. Psychosocial treatment was measured by any use and expenditures
      per user. The schizophrenia subscale of the Brief Psychiatric Rating Scale was
      used to measure consumer outcomes. RESULTS: Probabilities of antipsychotic use in
      the managed care areas were stable or increased compared with the other areas.
      The average number of months with filled prescriptions was unchanged. Consumers
      served under managed care were less likely to use psychosocial treatment, and
      additional decreases in treatment costs were noted in one area. Difference scores
      for the schizophrenia subscale showed no change or positive effects for the
      managed care areas. CONCLUSIONS: Within the Colorado managed care program,
      antipsychotic medication therapy was not impaired, despite significant decreases
      in the continuity or intensity of psychosocial treatment, and no reduction in
      symptom levels was noted. Mental health managed care does not inherently impair
      medication therapy. Patterns of medication use appeared to be better indicators
      of program success than psychosocial treatment patterns and were more consistent
      with outcomes.

PMID- 16282260
TI  - Demand for mental health care and changes in service use patterns in the
      Netherlands, 1979 to 1995.
AB  - OBJECTIVE: Mental health services appear increasingly incapable of satisfying the
      demand for care, which may cause some segments of the population to be less
      effectively reached. This study investigated the rates of use of mental health
      services in the Netherlands from 1979 to 1995 and examined whether particular
      sociodemographic groups made greater or lesser relative use of these services
      over time. METHODS: Data were derived from the Facilities Use Surveys, a series
      of Dutch cross-sectional population studies that have recorded household
      characteristics and service use since 1979. More than 28,000 households were
      included in the analyses. RESULTS: The overall use of mental health services
      virtually doubled from 1979 to 1995; a particularly steep rise was seen in the
      first half of the 1980s. Households that had one parent, that had low income,
      that were dependent on benefits, and that were younger all had greater odds of
      using both specialized mental health care (for example, prevention programs for
      mental health problems and psychotherapeutic and social psychiatric treatment
      offered by psychologists, psychotherapists, or psychiatrists) and social work
      services (for example, psychosocial counselling and practical support offered by
      social workers to people with social problems, such as housing, finances, and
      psychosocial issues). Households with low education were less likely to use
      specialized mental health care but were more likely to use social work services.
      Nonreligious households and urban households were more likely to use specialized
      mental health care and were equally likely to use social work services. Overall,
      these relative use patterns did not change over time. CONCLUSIONS: Despite
      greater pressures on mental health services and the many changes in service
      delivery in recent decades, relative patterns of help seeking and referral to
      mental health services have not varied systematically over time.

PMID- 16282261
TI  - Outcomes for long-term patients one year after discharge from a psychiatric
      hospital.
AB  - OBJECTIVES: The purpose of this study was to evaluate effects associated with
      moving patients from hospital to community-based settings, to compare persons who
      left the hospital with those who remained in the hospital, and to address the
      question of whether discharge reverses institutionalism in a sample of elderly
      long-stay psychiatric inpatients. METHODS: The hypotheses were that, compared
      with the control group of patients who stayed in the hospital, those who left
      would have significantly better mental states, social functioning, and social
      networks at follow-up; that community settings would provide a significantly
      better quality of environment than the hospital; and that discharged patients
      would express a preference for community care after discharge from the hospital.
      The study was a prospective nonrandomized controlled trial at Cane Hill, Friern,
      and Claybury Hospitals in England. Sixty long-term patients with schizophrenia
      who were discharged to community care were compared over time with matched
      controls (N=131). RESULTS: No overall differences were detected in the pattern or
      severity of symptoms between patients who were discharged from the hospital and
      those who were not, and no significant changes over time were noted. Significant
      improvements in social networks, patients' preference for community settings, and
      quality of clinical environment were noted. CONCLUSIONS: These results give
      qualified support for moving long-stay psychiatric patients from hospital to
      community settings.

PMID- 16282262
TI  - Relationship between cognition and work functioning among patients with
      schizophrenia in an urban area of India.
AB  - OBJECTIVE: Employment rates and work functioning are poor among patients with
      schizophrenia and are related to cognitive dysfunction. This study examined the
      relationship between work functioning and cognition, other clinical and
      demographic variables, and measures of social functioning among patients with
      schizophrenia in an urban area of India. METHODS: This study evaluated cognitive
      dysfunction and work functioning among 88 patients with chronic schizophrenia.
      Attention, executive function, and memory were tested with a battery of
      neuropsychological tests. Work and social functions were evaluated with
      standardized instruments. RESULTS: Fifty-nine patients (67 percent) were
      employed, most in a mainstream environment. Moderate to significant work
      dysfunction was present among 21 patients (24 percent). When multivariate
      analysis was performed, cognitive deficits did not relate significantly to
      current employment status or to level of performance at work. Negative symptoms
      predicted employment status, and poor social functioning predicted poor work
      performance. CONCLUSIONS: The relationship between work and cognitive status in
      schizophrenia was not as strong as has been previously reported in this
      population. It was speculated that social factors, such as the compelling need to
      be employed, a supportive work environment, and the number of years of formal
      education, were factors underlying the high level of work functioning in this
      group despite cognitive deficits.

PMID- 16282263
TI  - Outcomes-based funding for vocational services and employment of people with
      mental health conditions.
AB  - OBJECTIVE: This study explored the likelihood of and identified the factors
      related to securing and sustaining jobs for people with psychiatric disabilities
      in New York State who received vocational services through an outcomes-based
      reimbursement program. METHODS: Quantitative and qualitative data were collected
      over two years to characterize placement and retention through the performance
      based contracting demonstration. Seven social service agencies located statewide
      were contracted by the New York State Office of Mental Health to provide
      vocational services to people with mental health conditions through the
      performance-based contracting milestone structure, which established incremental
      steps toward the goal of sustained integrated competitive employment at which
      providers were reimbursed. Intake was continuous throughout the demonstration
      period, from December 2000 to December 2002. Key outcomes included placement in
      employment, time to placement, and job retention. RESULTS: Data were examined for
      the 171 participants who were still active in the demonstration at the end of the
      study period. A total of 108 participants (63 percent) were successful in
      securing jobs. Among those placed, 79 (73 percent) retained work at the end of
      the demonstration, a rate comparable to other best-practice models. Factors
      related to these outcomes included number of provider hours spent assisting
      consumers weekly, length of time to placement, consumer enrollment in the state's
      rehabilitation services program, and quality of the jobs developed. CONCLUSIONS:
      Outcomes funding was associated with successful employment for people with
      psychiatric disabilities. The performance-based funding structure may encourage
      providers to work more intensively with consumers early in the placement process,
      find jobs that consumers want to keep, and coordinate more effectively with the
      state rehabilitation agency.

PMID- 16282264
TI  - A case report of the conversion of sheltered employment to evidence-based
      supported employment in Canada.
AB  - This case report describes the transformation of a sheltered workshop program to
      a program that provides evidence-based supported employment services in
      partnership with five community treatment teams. Over a 15-year period, a
      Canadian nonprofit agency that provides employment services for persons with
      severe mental illness made a series of programmatic changes to increase the
      effectiveness of the services. The agency initially modified its facility-based
      sheltered workshop to include a prevocationally oriented work preparation
      program, later added brokered supported employment services, and finally
      completely transformed its organization by relocating its vocational
      rehabilitation counselors to five community mental health teams, in order to
      implement an evidence-based supported employment program that is based on the
      individual placement and support model. During the initial period in which the
      sheltered employment program was utilized, less than 5 percent of clients who
      were unemployed when they entered the workshop achieved competitive employment
      annually. The annual competitive employment rate did not increase during the
      prevocational phase; it increased during the brokered supported employment phase
      but did not exceed 25 percent. By contrast, after shifting to evidence-based
      supported employment, 84 (50 percent) of 168 unemployed clients who received
      between six and 27 months of individual placement and support services achieved
      competitive employment. This article also documents the role of agency planning
      and commitment quality improvement in implementing change.

PMID- 16282265
TI  - Psychosis seminars: an unconventional approach.

PMID- 16282266
TI  - Brief reports: the fidelity of supported employment implementation in Canada and
      the United States.
AB  - Supported employment has been documented in the United States as an evidence
      based practice that helps people with severe mental illness obtain and maintain
      employment. The evidence is strongest for the programs that follow the individual
      placement and support model. This brief report examines the degree to which
      supported employment programs in British Columbia, Canada, are similar to those
      in the United States. Data from the Quality of Supported Employment
      Implementation Scale were compiled in 2003 for ten supported employment programs
      from vocational agencies in British Columbia and were compared with data from 106
      supported employment programs and 38 non-supported employment programs in the
      United States. Overall, the Canadian supported employment programs that followed
      the individual placement and support model had the highest fidelity.

PMID- 16282267
TI  - Physicians' and patients' involvement in relapse prevention with antipsychotics
      in schizophrenia.
AB  - The purpose of this study was to assess the current status of relapse prevention
      in schizophrenia. Fifty hospital psychiatrists in Germany were interviewed about
      100 currently treated inpatients. The patients were also interviewed about their
      knowledge of maintenance therapy. For 75 percent of their patients, physicians
      fulfilled guideline recommendations when indicating the planned duration of
      antipsychotic maintenance therapy. However, these recommendations were not
      routinely communicated to the patients, and target interventions, such as
      psychoeducation, to guarantee continuous antipsychotic therapy were seldom used.
      Accordingly, patients' knowledge of the optimal duration of maintenance therapy
      was poor.

PMID- 16282268
TI  - Fidelity of an outreach treatment program for chronic crack abusers in the
      Netherlands to the ACT model.
AB  - This study evaluated an effective outreach treatment program in the Netherlands
      for chronic, high-risk crack abusers on its adherence to the assertive community
      treatment model. Fidelity was tested on 25 criteria of the Dartmouth Assertive
      Community Treatment Scale. Adherence was high on several factors: a small
      caseload, staff capacity, a nurse and a substance abuse specialist on staff,
      explicit admission criteria, low intake rate, and intensity of service. Future
      programs that focus on treating crack addiction should implement these
      components. The outreach treatment program showed low adherence to the assertive
      community treatment model for including a psychiatrist and a vocational
      specialist, both of which are important factors that should be implemented in
      future programs. Other factors were observed to be important for treating this
      population: a strong focus on the client-therapist relationship, stagewise
      substance abuse treatment, and on-the-spot incentives to keep this population
      involved in treatment.

PMID- 16282269
TI  - Regional collaboration in reconstruction of mental health services in Bosnia and
      Herzegovina.
AB  - The war in the former Yugoslavia between 1991 and 1995 destroyed the mainly
      hospital-based mental health care system in Bosnia and Herzegovina. This report
      summarizes the situation before and after the war and describes efforts to
      rebuild and reform mental health services under politically and economically
      challenging conditions. As a result of these efforts, there are now 39
      multidisciplinary community mental health centers that are linked to primary care
      and that aim to provide prevention, treatment, and rehabilitation of mental
      disorders. The reform process has been supported by international initiatives and
      is now continuing in collaboration with other countries in South Eastern Europe.

PMID- 16282270
TI  - Training program in mental illness for immigration officers.

PMID- 16282271
TI  - An intensive mental health unit for adolescents in the correctional setting.

PMID- 16282272
TI  - Use of practitioner-based alternative therapies by psychiatric outpatients.

PMID- 16282273
TI  - Criminal arrests and the threshold for competence.

PMID- 16282274
TI  - Psychiatrists' acceptance of Medicaid patients.

PMID- 16282276
TI  - Visual dysfunction in Parkinson disease without dementia.
AB  - OBJECTIVE: To determine the profiles of visual dysfunction and their relationship
      to motor and cognitive dysfunction and to disability in mild to moderate
      Parkinson disease (PD) without dementia. METHODS: Seventy-six independently
      living participants with mild to moderate PD and 161 neurologically normal older
      adults were studied using a comprehensive battery to assess visual acuity,
      contrast sensitivity (CS), visual speed of processing and attention, spatial and
      motion perception, visual and verbal memory, visuoconstructional abilities,
      executive functions, depression, and motor function. RESULTS: Participants with
      PD scored significantly worse on all tests of vision and cognition compared with
      normal elderly persons. Reduced CS contributed to deficits on tests of spatial
      and motion perception and attention in participants with PD. Impairments in
      visual attention and spatial perception predicted worse cognitive function. Worse
      performances on tests of visual speed of processing and attention, spatial and
      motion perception, visual construction, and executive functions correlated with
      measures of postural instability and gait difficulty (in the Motor section of the
      Unified Parkinson's Disease Rating Scale). Impairments in motor function, visual
      memory, mood, and executive functions predicted worse disability as measured by
      Schwab-England Activities of Daily Living Scale. CONCLUSIONS: Patients with mild
      to moderate Parkinson disease showed impaired visual perception and cognition
      compared with elderly control subjects. Visual dysfunction contributes to
      parkinsonian disability through its influences on cognition and locomotion.

PMID- 16282278
TI  - The Alexander Project: the benefits from a decade of surveillance.
AB  - The Alexander Project, initiated in 1992 as an international, multicentre,
      longitudinal surveillance study of antimicrobial susceptibility among common
      respiratory pathogens, has been pivotal in defining the role of global
      surveillance. At the time, there were few studies in which data were collected in
      a way that allowed meaningful comparisons to be made between studies, locations
      or over time. The project instituted the use of a central laboratory and
      standardized methods for the collection of isolates and determination of
      susceptibility, and this was continued with the addition of two further reference
      laboratories. Data from the study have provided a resource for measuring trends
      in the susceptibility patterns of Streptococcus pneumoniae, Haemophilus
      influenzae and Moraxella catarrhalis at country, regional and global levels.
      Determination and publication of quantitative MICs enabled detailed assessment of
      changes in susceptibility distributions and assessment of microbiological and
      potential clinical susceptibility using different breakpoints, including those
      based on pharmacokinetic/pharmacodynamic parameters. Comparisons of antimicrobial
      usage patterns and resistance prevalences over time allowed hypotheses to be
      examined with respect to the role of quantity and type of antimicrobial use in
      the selection and spread of resistance. The resulting collection of isolates has
      provided a valuable resource for molecular studies into the evolution of
      resistance over time and location; a substantial proportion of this collection is
      now in the public domain. This paper reviews the 10 years of the Alexander
      Project and the benefits it has brought to an understanding of the evolution of
      antibacterial resistance in community respiratory bacteria.

PMID- 16282279
TI  - Concepts in the prevention of adenocarcinoma of the distal esophagus and proximal
      stomach.
AB  - For decades, the incidence rates for squamous cell carcinoma of the esophagus and
      adenocarcinoma of the distal stomach have been declining while the rates for
      adenocarcinomas of the esophagus and gastric cardia have increased profoundly.
      Recent studies have shown that the gastroesophageal junction (GEJ) is regularly
      exposed to concentrated gastric acid and to a variety of nitrosating species,
      noxious agents that may contribute to carcinogenesis in this region. For
      adenocarcinomas that straddle the GEJ, it can be difficult to determine whether
      the tumor originated in the esophagus or in the gastric cardia. This
      classification problem hampers studies on the epidemiology and pathogenesis of
      GEJ tumors. Current concepts in the prevention of cancers of the distal esophagus
      and proximal stomach have emerged from advances in our understanding of the
      specific molecular events that occur during the evolution of these tumors. This
      report reviews those events and focuses on current concepts in the prevention of
      adenocarcinomas at the GEJ. The similarities and differences in risk factors,
      molecular pathogenesis, and in preventive strategies for adenocarcinomas of the
      esophagus and gastric cardia are highlighted.

PMID- 16282280
TI  - Multimodality approaches for pancreatic cancer.
AB  - The role of combined-modality therapy for pancreatic cancer is evolving with the
      recent development and completion of major, multi-institutional clinical trials.
      One of the challenges for the busy clinician is to appreciate the variation in
      staging, surgical expertise, and application of either definitive
      chemoradiotherapy or adjuvant chemoradiotherapy for local and/or regionally
      advanced disease. Our aim is to summarize the current state-of-the-art management
      and future directions regarding the multimodality approach to pancreatic cancer.

PMID- 16282281
TI  - Staging non-Hodgkin lymphoma.
AB  - Non-Hodgkin Lymphomas are always treatable and frequently curable malignancies.
      However, choosing the most appropriate therapy requires accurate diagnosis and a
      careful staging evaluation. New patients with non-Hodgkin Lymphoma should have
      their tumors classified using the World Health Organization classification. The
      specific choice of therapy is dependent on a careful staging evaluation. Patients
      with non-Hodgkin Lymphoma are assigned an anatomic stage using the Ann Arbor
      system. However, patients should also be classified using the International
      Prognostic Index. New insights into the biology of the lymphomas in the coming
      years might well improve our ability to evaluate patients and choose therapy.

PMID- 16282283
TI  - Cancer connection.

PMID- 16282284
TI  - Bionic grandma.

PMID- 16282285
TI  - Mitochondrial genetics of aging: intergenomic conflict resolution.
AB  - Mitochondria are the organelles of aerobic respiration. They consume the oxygen
      we breathe to stay alive and generate energy for cells to function. But oxygen
      can be dangerous. Indeed, mitochondria generate the majority of reactive oxygen
      species that are prime suspects among the causes of aging. Mitochondria have been
      influential elements of evolving eukaryotic cells for perhaps 2 billion years,
      since a eubacterium fused with an archaebacterium. The picture that has emerged
      from this long history of genomic fusion is that of a complex network of nuclear
      mitochondrial cross-talk. Here, we discuss the biochemical and genetic conflicts
      between mitochondria and nucleus, which have shaped the role of mitochondria in
      aging, and point to new paths for further investigations.

PMID- 16282286
TI  - Amodiaquine and combination chemotherapy for malaria.

PMID- 16282287
TI  - Malaria, not down and certainly not out.

PMID- 16282288
TI  - Amodiaquine, sulfadoxine-pyrimethamine, and combination therapy for uncomplicated
      falciparum malaria: a randomized controlled trial from Burkina Faso.
AB  - Increasing resistance to chloroquine necessitates the evaluation of other
      antimalarial therapies in Africa. We compared the efficacies of amodiaquine (AQ),
      sulfadoxine-pyrimethamine (SP), and AQ + SP for the treatment of uncomplicated
      falciparum malaria in a randomized trial of patients 6 months of age or older in
      Bobo-Dioulasso, Burkina Faso. Of the 944 patients enrolled, 829 (88%; 53% under 5
      years of age) were assigned 28-day efficacy outcomes. For all regimens, early
      treatment failures were uncommon (< 2%). Considering all treatment failures based
      on WHO criteria, AQ + SP was most efficacious (failures in 4.2%), followed by SP
      (9.1%) and AQ (17.9%; P < 0.02 for all pairwise comparisons). Considering only
      clinical failures, relative efficacies were similar (failures in 2.1% with AQ +
      SP, 6.5% with SP, and 13.2% with AQ; P < 0.02 for all pairwise comparisons). The
      risk of recrudescence was lower with AQ + SP (2.1%) compared with SP (6.1%, P =
      0.02) and AQ (8.1%, P = 0.001). Risks of new infection were lower with AQ + SP
      (2.1%) and SP (2.4%) compared with AQ (9.1%, P < 0.001 for both comparisons). No
      serious adverse events were seen. AQ + SP appears to offer a highly effective,
      inexpensive, and available therapy for the treatment of uncomplicated malaria in
      Burkina Faso.

PMID- 16282289
TI  - Drug resistance and genetic diversity of Plasmodium falciparum parasites from
      suriname.
AB  - Plasmodium falciparum in Suriname was studied for the presence of drug resistance
      and genetic variation in blood samples of 86 patients with symptomatic malaria.
      Drug resistance was predicted by determining point mutations in the chloroquine
      resistance marker of the P. falciparum chloroquine resistance transporter (pfcrt)
      gene (codon 76) and the pyrimethamine-sulfadoxine resistance markers in the
      dihydrofolate reductase (dhfr) gene (codons 16, 51, 59, 108, and 164) and
      dihydropteroate synthase (dhps) gene (codons 436, 437, 540, 581, and 613).
      Genetic variability was determined by sequence analysis of the polymorphic
      segments of the merozoite surface protein 2 (msp-2) and glutamate-rich protein
      (glurp) genes. Mutations in the pfcrt, dhps, and dhfr genes were found in all
      samples tested, suggesting that resistance to chloroquine and antifolate drugs is
      present at a high frequency. A low number of alleles was found for the msp-2 and
      glurp genes. This indicates limited genetic diversity and, based on geographic
      data, a genetically homogeneous P. falciparum population in Suriname.

PMID- 16282290
TI  - Prevalence of Plasmodium falciparum mutations associated with antimalarial drug
      resistance during an epidemic in Kuna Yala, Panama, Central America.
AB  - A molecular epidemiology study was conducted to determine the distribution of
      antimalarial drug resistance alleles among field isolates of Plasmodium
      falciparum. Samples were obtained during an epidemic affecting Kuna Amerindians
      in Panama. A high prevalence of mutations associated with chloroquine,
      pyrimethamine, and sulfadoxine was observed. Genotype analysis of msp2 revealed a
      low genetic diversity of P. falciparum parasites circulating in the studied area.
      The public health implications of these findings for the Central American region
      are discussed.

PMID- 16282291
TI  - Randomized, controlled, double-blind trial of daily oral azithromycin in adults
      for the prophylaxis of Plasmodium vivax malaria in Western Thailand.
AB  - We assessed the prophylactic efficacy of azithromycin (250 mg/day) against
      malaria in 276 adults in western Thailand in a randomized, double-blind, placebo
      controlled trial. After antimalarial suppressive treatment, volunteers were
      randomized in a 2:1 ratio to either the azithromycin or placebo, respectively.
      Study medication was given for an average of 74 days. The azithromycin group (n =
      179) had five endpoint parasitemias (1 Plasmodium vivax and 4 P. falciparum), and
      the placebo group (n = 97) had 28 endpoint parasitemias (21 P. vivax, 5 P.
      falciparum, and 2 mixed infections). Adverse events and compliance and withdrawal
      rates were similar in both groups. The protective efficacy (PE) of azithromycin
      was 98% for P. vivax (95% confidence interval [CI] = 88-100%). There were too few
      cases to reliably estimate the efficacy of azithromycin for P. falciparum (PE
      =71%, 95% C =-14-94%). We conclude that daily azithromycin was safe, well
      tolerated, and had a high efficacy for the prevention of P. vivax malaria.

PMID- 16282292
TI  - Evaluation of a real-time polymerase chain reaction assay for the diagnosis of
      malaria in patients from Thailand.
AB  - We compared the diagnosis of malaria in 297 patients from Thailand by a real-time
      polymerase chain reaction (PCR) assay using the LightCycler with conventional
      microscopy using Giemsa-stained thick and thin blood films. The PCR assay can be
      completed in one hour and has the potential to detect and identify four species
      of Plasmodium in a single reaction by use of melting temperature curve analysis
      (however, we did not detect Plasmodium ovale in this study). Blood was collected,
      stored, and transported on IsoCode STIX, which provide a stable matrix for the
      archiving and rapid simple extraction of DNA. A genus-specific primer set
      corresponding to the 18S ribosomal RNA was used to amplify the target sequence.
      Fluorescence resonance energy technology hybridization probes were designed for
      P. falciparum over a region containing basepair mismatches, which allowed
      differentiation of the other Plasmodium species. The PCR results correlated with
      the microscopic results in 282 (95%) of 297 patient specimens. Most of these were
      single-species infections caused by P. vivax (150) and P. falciparum (120), along
      with 5 P. malariae, 2 mixed infections (P. falciparum and P. vivax), and 5
      negative specimens. No negative microscopy specimens were positive by PCR (100%
      specificity for detection of any Plasmodium). The 15 discrepant results could not
      be resolved, but given the subjective nature of microscopy and the analytical
      objectivity of the PCR, the PCR results may be correct. The ability of the PCR
      method to detect mixed infections or to detect P. ovale could not be determined
      in this study. Within the limitations of initial equipment costs, this real-time
      PCR assay is a rapid, accurate, and efficient method for the specific diagnosis
      of malaria. It may have application in clinical laboratories, as well as in
      epidemiologic studies and antimalarial efficacy trials.

PMID- 16282293
TI  - Evaluation of a rapid diagnostic test for assessing the burden of malaria at
      delivery in India.
AB  - All pregnant women who came for delivery at a district hospital in Mandla and a
      civil hospital in Maihar were screened for Plasmodium falciparum (placental
      parasitemia using a rapid test and microscopy and peripheral and umbilical cord
      parasitemia using microscopy alone). Two rapid diagnostic tests (RDTs), Paracheck
      Pf and ParaHITf, were used. At Mandla, the sensitivity and specificity of the
      Paracheck Pf for P. falciparum were 93% and 84%, respectively. The positive
      predictive values (PPVs) and negative predictive values (NPVs) were 50% and 99%,
      respectively. At Maihar, the sensitivity and specificity of the ParaHITf for P.
      falciparum were 87.5% and 97%, respectively. The PPVs and NPVs were 75.4% and
      98.7%, respectively. Placental infection was significantly associated with low
      birth weight. The RDTs for the identification of P. falciparum were more
      sensitive in placental blood than the placental blood smear by microscopy. Thus,
      the RDTs should be useful for rapid assessment of malaria at delivery.

PMID- 16282294
TI  - Protective efficacy of lambda-cyhalothrin treated nets in Anopheles gambiae
      pyrethroid resistance areas of Cote d'Ivoire.
AB  - The efficacy of nets treated with lambda-cyhalothrin, a pyrethroid insecticide,
      on malaria infection and disease was assessed for the first time at the community
      level in Anopheles gambiae pyrethroid resistance areas. The study was carried out
      in northern Cote d'Ivoire, which is an area of kdr resistance. Four pairs of
      villages were selected and matched according to demographic, sociological, and
      ecological criteria. Among each pair, a village was randomly allocated to receive
      mosquito nets. More than 80% of beds were covered with nets treated with lambda
      cyhalothrin and retreated after 6 months. In each village, 54 children aged 0-59
      months were randomly selected and clinically monitored for 8 periods of 7 days
      throughout the year. Results showed that the efficacy of treated nets was
      maintained with a reduction of the prevalence of asymptomatic malaria infection
      by 12% and an estimated protective efficacy against malaria disease of 56%.

PMID- 16282295
TI  - Comparative infectivity of Babesia divergens and a zoonotic Babesia divergens
      like parasite in cattle.
AB  - Babesia divergens-like parasites identified in human babesiosis cases in Missouri
      and Kentucky and in eastern cottontail rabbits (Sylvilagus floridanus) on
      Nantucket Island, Massachusetts, share identical small subunit ribosomal RNA gene
      sequences. This sequence is 99.8% identical to that of Babesia divergens,
      suggesting that the U.S. parasite may be B. divergens, a causative agent of human
      and bovine babesiosis in Europe. Holstein-Friesian calves were inoculated with
      cultured Nantucket Island Babesia sp. (NR831) and B. divergens parasites and
      monitored by clinical signs, Giemsa-stained blood films, PCR, and culture. The
      NR831 recipients did not exhibit clinical signs of infection and remained
      negative for all assays. The B. divergens recipients developed clinical
      infections and became positive by all assays. NR831 recipients were fully
      susceptible upon challenge inoculation with B. divergens. This study confirms
      that the Nantucket Island Babesia sp. is not conspecific with B. divergens based
      on host specificity for cattle.

PMID- 16282296
TI  - A phase II dose-increasing study of sitamaquine for the treatment of visceral
      leishmaniasis in Kenya.
AB  - Sitamaquine (WR6026) is an 8-aminoquinoline in development for the oral treatment
      of visceral leishmaniasis (VL). This was an open-label, dose-increasing study to
      determine the dose-response and safety profile for sitamaquine in Kenyan patients
      with VL caused by Leishmania donovani. Patients (mean age 15.9 [range = 5-47]
      years) received sitamaquine daily for 28 days at one of four doses: 1.75 (n =
      12), 2.0 (n = 61), 2.5 (n = 12), or 3.0 (n = 12) mg/kg/day. The primary efficacy
      outcome was cure (absence of parasites on splenic aspirate) in the intent-to
      treat population at day 180. Cure was achieved in 79 (83%) of 95 patients
      overall, and in 11 (92%) of 12, 49 (80%) of 61, 9 (82%) of 11, and 10 (91%) of 11
      patients at sitamaquine doses of 1.75, 2.0, 2.5, or 3.0 mg/kg/day, respectively.
      The most frequent adverse events during active treatment were abdominal pain (12
      [12%] of 97) and headache (11 [11%] of 97), and one patient in each of the 2.5
      mg/kg/day and 3.0 mg/kg/day dose groups had a severe renal adverse event. The
      effects of sitamaquine on the kidney need further investigation. Sitamaquine was
      efficacious and generally well tolerated in Kenyan patients with VL.

PMID- 16282297
TI  - Concomitant parasitism: bancroftian filariasis and intestinal helminths and
      response to albendazole.
AB  - Subjects in an disease-endemic area in Orissa, India concomitantly infected with
      filariasis and intestinal helminths had significantly lower intensity of filarial
      infection in comparison with those who were infected only with filariasis.
      Administration of albendazole resulted in a significant decrease in the
      prevalence of filarial antigenemia in subjects concomitantly infected with
      intestinal helminths, but produced little change in this infection measure in
      subjects infected only with Wuchereria bancrofti. These results indicate that
      intestinal helminths could play a role in the anti-filarial activity of
      albendazole, most probably by depressing filarial infection intensity in co
      infected individuals. Confirmation of these findings in a larger cohort may yield
      important new insights regarding the role of using albendazole in the ongoing
      intervention programs for the control of lymphatic filariasis.

PMID- 16282298
TI  - Effects of ivermectin and diethylcarbamazine on microfilariae and overall
      microfilaria production in bancroftian filariasis.
AB  - Ivermectin and diethylcarbamazine (DEC) are used in mass treatment programs for
      the elimination of lymphatic filariasis because of their strong effects on
      microfilaremia. However, the effects of treatment on adult worms and the degree
      of individual variation in efficacy are unclear. We analyzed series of
      microfilaria (Mf) counts from individuals treated with a single dose of 400
      microg/kg ivermectin or 6 mg/kg DEC (N = 23 in each group; 1 year follow-up). For
      each individual, we estimated the microfilaricidal effect and the reduction in
      overall Mf production (e.g., caused by death or sterilization of worms, or
      inhibited Mf release from the female worm uterus). Ivermectin on average killed
      96% of Mf and reduced Mf production by 82%. DEC killed 57% of Mf and reduced Mf
      production by 67%, with some individuals responding very poorly. The strong
      reduction in overall Mf production is good news for control of lymphatic
      filariasis, but the prospects of elimination will be diminished if part of the
      population systematically responds poorly to treatment.

PMID- 16282299
TI  - The Leogane, Haiti demonstration project: decreased microfilaremia and program
      costs after three years of mass drug administration.
AB  - To support the global program to eliminate lymphatic filariasis (LF), well
      monitored demonstration projects are important for defining the relationship
      between coverage and reductions in microfilaremia. We are using mass treatment
      with diethylcarbamazine (DEC) and albendazole in an effort to eliminate LF from
      Leogane, Haiti. Wuchereria bancrofti microfilaremia prevalence at baseline ranged
      from 0.8% to 15.9% in four sentinel sites. After three rounds of DEC-albendazole
      mass drug administration (MDA), both microfilaremia prevalence and intensity
      decreased dramatically. Mild and moderate adverse reactions after treatment were
      common, especially after the first MDA, but decreased after subsequent MDAs. Drug
      coverage for the first year was estimated to be 72%, but concerns about adverse
      reactions appeared to decrease drug coverage in the second MDA. As a result of
      community education efforts that focused on providing a greater understanding of
      adverse reactions, coverage increased dramatically for the third round. Program
      efficiency increased substantially; the costs per person treated for three rounds
      of MDA were 2.23 US dollars, 1.96 US dollars, and 1.30 US dollars per person,
      respectively. The Leogane experience highlights the importance of adapting
      community education and mobilization campaigns to achieve and maintain good
      coverage.

PMID- 16282300
TI  - Detection and differentiation of filarial parasites by universal primers and
      polymerase chain reaction-restriction fragment length polymorphism analysis.
AB  - Filarial nematode parasites are a serious cause of morbidity in humans and
      animals. Identification of filarial infection using traditional morphologic
      criteria can be difficult and lead to misdiagnosis. We report on a polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based method
      to detect and differentiate a broad range of filarial species in a single PCR.
      The first internal transcribed spacer 1 (ITS1) along with the flanking 18S and
      5.8S ribosomal DNA (rDNA) were isolated and cloned from Wuchereria bancrofti,
      Brugia malayi, and Brugia pahangi. Sequence analysis identified conserved sites
      in the 18S and 5.8S rDNA sequence that could be used as universal priming sites
      to generate ITS1-distinctive PCR products that were useful for distinguishing
      filariae at the genus level. The addition of a digestion of the ITS1 PCR product
      with the restriction endonuclease Ase I generated a fragment profile that allowed
      differentiation down to the species level for W. bancrofti, B. malayi, B.
      pahangi, Dirofilaria immitis, and D. repens. The PCR-RFLP of ITS1 rDNA will be
      useful in diagnosing and differentiating filarial parasites in human, animal
      reservoir hosts, and mosquito vectors in disease-endemic areas.

PMID- 16282302
TI  - Parenteral administration of ivermectin in a patient with disseminated
      strongyloidiasis.
AB  - We report the case of a 23-year-old Caribbean man with disseminated
      strongyloidiasis (co-infected with human T cell lymphotropic virus I/II)), severe
      hypoalbuminemia, and a paralytic ileus. Subcutaneous ivermectin (200 microg/kg)
      was administered daily for 14 days because of the inability to effectively
      administer oral albendazole and oral ivermectin. Three hours after the third
      daily dose of oral ivermectin, the serum ivermectin concentration was only 0.8
      ng/mL, but it increased several fold to 5.8 ng/mL 16 hours after the first dose
      of subcutaneous ivermectin. During the course of subcutaneous treatment,
      ivermectin clearance was higher than expected (46.0 L/hour, normal = 31.8
      L/hour). This is likely the result of severe hypoalbuminemia since ivermectin is
      highly protein bound. The ability to achieve adequate levels of ivermectin after
      oral administration in patients with disseminated strongyloidiasis may be
      impaired, highlighting the need for alternative routes of administration of
      ivermectin in these patients.

PMID- 16282301
TI  - Cost-effectiveness of Chagas disease interventions in latin america and the
      Caribbean: Markov models.
AB  - Chagas disease is a parasitic disease in Latin America. Despite vector control
      programs that have reduced incidence by 70%, there are at least 12-14 million
      prevalent cases. We used a Markov model to examine strategies for control and
      treatment of Chagas disease that compared annual costs, life expectancies, and
      cost-effectiveness of three vector control and drug treatment strategies. Vector
      control programs alone and vector control plus drug treatment are dominant over
      no vector control (i.e., less costly and save more lives), and vector control
      plus drug is highly cost-effective compared with vector control alone. We
      demonstrated expected changes in deaths over time resulting from various
      prevention approaches. Vector control affects primarily incidence, not decreasing
      deaths and prevalence for 30 years, while drug treatment affects prevalence and
      deaths immediately. The best strategy to combat Chagas disease is combinations of
      vector control and a potential new drug.

PMID- 16282303
TI  - Detection of excretory/secretory coproantigens in experimental hookworm
      infection.
AB  - This report describes the detection of hookworm excretory/secretory (ES) antigens
      in soluble hamster fecal extracts by an enzyme-linked immunosorbent assay
      (ELISA). A rabbit polyclonal IgG antibody against Ancylostoma ceylanicum ES was
      used to capture hookworm coproantigens that were then detected using pooled, high
      titer, infected hamster serum. The ELISA was capable of detecting ES proteins
      over a range of 10 ng/mL to 10 mug/mL when the antigens were diluted in buffer or
      uninfected fecal extract, and ES could be detected in infected hamster feces at
      dilutions up to 1:256. Examination of the kinetics of coproantigen production
      demonstrated that detectable amounts of ES were produced as early as four days
      after A. ceylanicum infection, whereas fecal eggs were not observed until day 17.
      Moreover, fecal ES levels correlated well with intestinal worm burden and could
      be detected in wet or dry stool samples stored for 14 days over a temperature
      range of -80 degrees C to 37 degrees C. The fecal ELISA was then adapted to
      analyze the excretion of AceES-2, a novel immunogenic ES protein recently cloned
      from A. ceylanicum cDNA. AceES-2 was found to be excreted in feces with kinetics
      similar to that of whole ES. Examination of individual hookworm antigens by this
      method will provide new insights into the molecular host-parasite interaction and
      may form the basis for future diagnostic methods.

PMID- 16282304
TI  - Cryptosporidiosis and microsporidiosis in ugandan children with persistent
      diarrhea with and without concurrent infection with the human immunodeficiency
      virus.
AB  - Cryptosporidium spp. and Enterocytozoon bieneusi are enteric pathogens that have
      emerged as significant causes of persistent diarrhea (PD) in immunologically
      compromised individuals particularly in association with HIV/AIDS. We conducted a
      cross-sectional study on the clinical epidemiology of E. bieneusi and
      Cryptosporidium in children with PD, with and without HIV/AIDS, attending
      Uganda's Mulago National Referral Hospital. Two hundred forty-three children aged
      < 60 months, admitted between November 2002 and May 2003 with PD (> 14 days),
      were analyzed for HIV status and CD4 lymphocyte counts, and stools were screened
      for the presence of E. bieneusi and Cryptosporidium by microscopy and positive
      samples genotyped by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) analysis. Eighty (32.9%) of the children were excreting
      E. bieneusi, and 76 (31.3%) were excreting Cryptosporidium. Ninety-one of the 243
      children had HIV, of who 70 (76.9%) had E. bieneusi, versus 10 (6.6%) of the 152
      without (odds ratio = 47.33; 95% CI = 19.88 to 115.97), while 67 (73.6%) had
      Cryptosporidium, versus 9 (5.9%) without (odds ratio = 44.36; 95% CI = 18.39 to
      110.40). Children with counts < 25% CD4 cells were more likely to have either E.
      bieneusi (odds ratio = 7.42; 95% CI = 3.77 to 14.69) or Cryptosporidium (odds
      ratio = 6.45; 95% CI = 3.28 to 12.76) than those with higher CD4 percentages.
      However, only HIV status was independently associated with either Cryptosporidium
      or E. bieneusi. Among the 243 children with PD, 67 (27.8%) were infected with
      both enteric pathogens, with HIV being the only independent predictor of
      coinfection. Finally, some 81% of HIV-infected children with PD excreted one or
      both organisms, compared with only 10% of children with PD testing negative for
      HIV. Seventy-four percent of isolates were C. hominis, the anthroponotic species,
      17% were C. parvum, the zoonotic species, and 8% were a mixture of the two or
      others.

PMID- 16282306
TI  - Amebic colitis in asymptomatic subjects with positive fecal occult blood test
      results: clinical features different from symptomatic cases.
AB  - Amebiasis is a common parasitic infectious disease in developing countries. In
      developed countries, it is occasionally encountered in travelers to the tropics
      and in homosexual males. During the past eight years, we detected four cases of
      amebic colitis among 5,193 subjects who underwent colonoscopy because of positive
      fecal occult blood test results in a mass screening. All four cases did not have
      any abdominal symptoms. Ulcerative lesions were observed only in the cecum and
      ascending colon; another portion of the colon and rectum appeared normal. We may
      encounter amebic colitis during colonoscopic examination even in subjects who are
      asymptomatic.

PMID- 16282305
TI  - Effect of home-based water chlorination and safe storage on diarrhea among
      persons with human immunodeficiency virus in Uganda.
AB  - Diarrhea is frequent among persons infected with human immunodeficiency virus
      (HIV) but few interventions are available for people in Africa. We conducted a
      randomized controlled trial of a home-based, safe water intervention on the
      incidence and severity of diarrhea among persons with HIV living in rural Uganda.
      Between April 2001 and November 2002, households of 509 persons with HIV and
      1,521 HIV-negative household members received a closed-mouth plastic container, a
      dilute chlorine solution, and hygiene education (safe water system [SWS]) or
      simply hygiene education alone. After five months, HIV-positive participants
      received daily cotrimoxazole prophylaxis (160 mg of trimethoprim and 800 mg of
      sulfamethoxazole) and were followed for an additional 1.5 years. Persons with HIV
      using SWS had 25% fewer diarrhea episodes (adjusted incidence rate ratio [IRR] =
      0.75, 95% confidence interval [CI] = 0.59-0.94, P = 0.015), 33% fewer days with
      diarrhea (IRR = 0.67, 95% CI = 0.48-0.94, P = 0.021), and less visible blood or
      mucus in stools (28% versus 39%; P < 0.0001). The SWS was equally effective with
      or without cotrimoxazole prophylaxis (P = 0.73 for interaction), and together
      they reduced diarrhea episodes by 67% (IRR = 0.33, 95% CI = 0.24-0.46, P <
      0.0001), days with diarrhea by 54% (IRR = 0.46, 95% CI = 0.32-0.66, P < 0.0001),
      and days of work or school lost due to diarrhea by 47% (IRR = 0.53, 95% CI = 0.34
      0.83, P < 0.0056). A home-based safe water system reduced diarrhea frequency and
      severity among persons with HIV living in Africa and large scale implementation
      should be considered.

PMID- 16282307
TI  - Protection against scrub typhus by a plasmid vaccine encoding the 56-KD outer
      membrane protein antigen gene.
AB  - The 56-kD outer membrane protein of Orientia tsutsugamushi has previously been
      shown to be the immunodominant antigen in scrub typhus infections. Its gene was
      cloned into the DNA vaccine vector pVR1012 as a vaccine candidate (pKarp56). The
      in vitro expression of this 56-kD antigen by pKarp56 was confirmed in tissue
      culture by an indirect fluorescence assay and Western blot analysis. The initial
      antibody responses of mice immunized with varied doses of the pKarp56 were barely
      detected, but increases were observed after each of three subsequent booster
      immunizations. Although no protection was observed with a single immunization of
      pKarp56, after four immunizations, 60% of the mice survived a 1,000 x 50% lethal
      dose (LD(50)) challenge. These results specifically confirm the importance of the
      56-kD protein antigen in protective immunity against O. tsutsugamushi and
      demonstrate the feasibility of DNA vaccines for the prevention of scrub typhus.

PMID- 16282308
TI  - Evaluation of a new rapid immunochromatographic assay for serodiagnosis of acute
      hepatitis E infection.
AB  - A rapid and reliable diagnostic assay for acute hepatitis E virus (HEV) infection
      is needed. We evaluated a rapid, immunochromatographic assay for IgM antibodies
      to HEV (ASSURE HEV IgM Rapid Test) using acute-phase HEV samples (n = 200) from
      Indonesia and Nepal and convalescent-phase HEV samples (n = 70) from Nepal. Blood
      donors in Thailand (n = 100), individuals with hepatitis A (n = 80), hepatitis B
      (n = 45), and hepatitis C (n = 50) in Thailand and Nepal, acute-phase sera of
      individuals with Epstein-Barr virus infection (n = 20), and rheumatoid factor
      positive blood (n = 26) served as negative controls. The assay had a sensitivity
      of 93% (95% confidence interval [CI] = 88.5-96.1%) and a specificity of 99.7%
      (95% CI = 98.3-100%). The positive and negative predictive values were 99.5% (95%
      CI = 97.1-100%) and 95.8% (95% CI = 93.1-97.7%), respectively. These results
      suggest that this assay is a sensitive and specific tool for the rapid diagnosis
      of acute HEV infection.

PMID- 16282309
TI  - Q Fever pneumonia: are clarithromycin and moxifloxacin alternative treatments
      only?
AB  - Medical records of 77 patients with Q fever pneumonia that was serologically
      confirmed by enzyme-linked immunosorbent assay were studied to compare the
      clinical efficacy of doxycycline, clarithromycin, and moxifloxacin. The mean
      times to defervescence were 2.4 days for those receiving doxycycline, 1.9 days
      for those receiving clarithromycin, and 2.2 days for those receiving
      moxifloxacin. There were no interruptions of the regimens in any groups because
      of side effects, and outcome was favorable in all patients with no complications
      or relapses during follow-up. This efficacy of clarithromycin and moxifloxacin,
      together with their safety profiles, suggest that these alternative agents in the
      treatment of Q fever pneumonia could also be used as the first-line therapy.

PMID- 16282310
TI  - Field evaluation of the Meade Readiview handheld microscope for diagnosis of
      intestinal schistosomiasis in Ugandan school children.
AB  - A novel, inexpensive handheld microscope, the Meade Readiview, was evaluated for
      field diagnosis of intestinal schistosomiasis by comparison of sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      against conventional compound microscopy as part of a parasitologic survey in
      nine sentinel schools and a rapid mapping survey across 22 schools in Uganda.
      Fecal smears from 685 primary school children were examined and the overall
      prevalence of Schistosoma mansoni was 45%. However, prevalence by school ranged
      widely from 0% to 100%. For individual diagnosis the Readiview had a sensitivity
      of 85%, a specificity of 96%, a PPV of 95%, and an NPV of 88%. Due to the poorer
      movement control of the glass slide on the Readiview stage, fecal smears with
      less than four eggs could be overlooked. At the highest magnification (160x), egg
      like objects could be confounding. Estimating prevalence by school was usually
      within +/- 7% of that of conventional microscopy. Since the Readiview is more
      robust and portable, both in size and weight, and one-tenth as expensive as the
      traditional compound microscope, a change in the logistics and costs associated
      with field infection surveillance is possible. This inexpensive microscope is a
      pragmatic alternative to the compound microscope. It could play an important role
      in the collection of prevalence data to better guide anthelmintic drug delivery
      and also empower the diagnostic capacity of peripheral health centers where
      compound microscopes are few or absent.

PMID- 16282312
TI  - Enumerating leptospires using the coulter counter.
AB  - The currently accepted gold standard for enumeration of leptospires is tabulation
      of organisms using a Petroff-Hausser counting chamber and dark-field microscopy,
      a technically demanding, time-consuming technique. Quantification of leptospires
      with a Coulter counter produced reliable and reproducible counts, comparable to
      the counting chamber. This experiment demonstrates that the faster, less
      technically demanding Coulter counter may be an alternative to determine numbers
      of leptospires.

PMID- 16282311
TI  - Reduction of infectivity of schistosome cercariae by application of cercaricidal
      oil to water.
AB  - Schistosomiasis continues to plague populations living in disease-endemic areas,
      and exposure to infective cercariae results in more than 200 million cases
      worldwide. Laboratory experiments were conducted to test whether a cercaricidal
      film applied directly to the water surface can reduce viability of cercariae. A
      distillate from inexpensive cedarwood oil enriched for cedrol in a mixed oil
      fraction was formulated (1:5) with the surfactant Tween 80. When applied to the
      surface of clean and turbid water in test vessels, the formulation spread across
      and just below the air-water interface, causing inactivation of Schistosoma
      mansoni cercariae within minutes. The active ingredient was heat stable and
      reduced schistosome survival and infectivity by 90% and 99.2%, respectively in a
      mouse model. The effective dose (13 mug/cm(2)) was dependent on surface area
      rather than volume of water treated. We conclude that application of the
      biodegradable formulation to the surface of schistosome-infested waters may be an
      effective, economical, and safe means of reducing human infections.

PMID- 16282314
TI  - Primary tuberculosis of the breast mimicking carcinoma.
AB  - This report describes a well-documented case of primary, nodular-form
      tuberculosis of the breast that mimicked cancer in a 73-year-old patient. This is
      a disease that rarely affects the breast.

PMID- 16282313
TI  - Diversity of bat-associated Leptospira in the Peruvian Amazon inferred by
      bayesian phylogenetic analysis of 16S ribosomal DNA sequences.
AB  - The role of bats as potential sources of transmission to humans or as maintenance
      hosts of leptospires is poorly understood. We quantified the prevalence of
      leptospiral colonization in bats in the Peruvian Amazon in the vicinity of
      Iquitos, an area of high biologic diversity. Of 589 analyzed bats, culture (3 of
      589) and molecular evidence (20 of 589) of leptospiral colonization was found in
      the kidneys, yielding an overall colonization rate of 3.4%. Infection rates
      differed with habitat and location, and among different bat species. Bayesian
      analysis was used to infer phylogenic relationships of leptospiral 16S ribosomal
      DNA sequences. Tree topologies were consistent with groupings based on DNA-DNA
      hybridization studies. A diverse group of leptospires was found in peri-Iquitos
      bat populations including Leptospira interrogans (5 clones), L. kirschneri (1),
      L. borgpetersenii (4), L. fainei (1), and two previously undescribed leptospiral
      species (8). Although L. kirschenri and L. interrogans have been previously
      isolated from bats, this report is the first to describe L. borgpetersenii and L.
      fainei infection of bats. A wild animal reservoir of L. fainei has not been
      previously described. The detection in bats of the L. interrogans serovar
      Icterohemorrhagiae, a leptospire typically maintained by peridomestic rats,
      suggests a rodent-bat infection cycle. Bats in Iquitos maintain a genetically
      diverse group of leptospires. These results provide a solid basis for pursuing
      molecular epidemiologic studies of bat-associated Leptospira, a potentially new
      epidemiologic reservoir of transmission of leptospirosis to humans.

PMID- 16282315
TI  - Identification and characterization of Sarcoptes scabiei and Dermatophagoides
      pteronyssinus glutathione S-transferases: implication as a potential major
      allergen in crusted scabies.
AB  - The astigmatid mite Sarcoptes scabiei is the causative agent of scabies, a highly
      infectious parasitic disease of the skin. Although the mite causes marked
      hypersensitivity reactions, particularly in crusted (severe) scabies, little is
      known about the specific scabies mite molecules involved in such immunologic
      responses. We have identified six genes encoding scabies mite homologues of mu
      and delta-like glutathione S-transferases (GSTs) as well as novel house dust mite
      GSTs. A mu class S. scabiei GST was subcloned into a prokaryotic expression
      system. The purified recombinant protein rSsGST01 reacted strongly with IgE and
      IgG4 in sera from crusted scabies patients. This response was not observed with
      control antigens or with ordinary scabies and uninfested patient sera. In
      addition, the specific IgE response to rSsGST01 did not correlate with the total
      IgE level of the patient. These results suggest that GST may play a role in the
      pathophysiology associated with crusted scabies.

PMID- 16282316
TI  - Tetrodotoxication with nassauris glans: a possibility of tetrodotoxin spreading
      in marine products near Pratas Island.
AB  - Tetrodotoxication was observed in six patients who ate gastropods from the South
      China Sea near Pratas Island. The pathogenic gastropod was Nassauris glans, which
      had not been previously mentioned in human tetrodotoxication. An extremely high
      level of tetrodotoxin was found in the causative gastropods, and a variety of
      clinical signs were observed in the survivors. The postmortem autopsy of two
      patients showed severe distension and hypersecretion of the alimentary tract,
      suggestive of a cholinergic crisis as the cause of their early death. A
      recognition of education regarding the risk of tetrodotoxication by N. glans in
      the study area is important to prevent further tragedy. A retrospective review of
      the tetrodotoxication in this region may aid in understanding the changes and
      route of tetrodotoxication in marine products, and provide valuable information
      for preventive measures.

PMID- 16282317
TI  - Lepidopterism due to exposure to the moth Hylesia metabus in northeastern
      Venezuela.
AB  - Lepidopterism refers to a spectrum of medical conditions in humans that usually
      involves the skin and results from contact with the adult or larval forms of
      certain butterflies and moths. We analyzed the epidemiologic and clinical
      features associated with exposure to the moth Hylesia metabus between 1970 and
      2002 in the Cajigal district, Sucre, Venezuela. Fifty cases of lepidopterism
      mostly affecting individuals under 18 years of age were identified during this
      period and manifested as pruritic dermatitis with or without associated
      respiratory symptoms. With increased travel to endemic areas of lepidopterism,
      travel and tropical medicine practitioners should be aware of the clinical
      spectrum of this condition.

PMID- 16282318
TI  - An Arabidopsis Fip1 homolog interacts with RNA and provides conceptual links with
      a number of other polyadenylation factor subunits.
AB  - The protein Fip1 is an important subunit of the eukaryotic polyadenylation
      apparatus, since it provides a bridge of sorts between poly(A) polymerase, other
      subunits of the polyadenylation apparatus, and the substrate RNA. In this study,
      a previously unreported Arabidopsis Fip1 homolog is characterized. The gene for
      this protein resides on chromosome V and encodes a 1196-amino acid polypeptide.
      Yeast two-hybrid and in vitro assays indicate that the N-terminal 137 amino acids
      of the Arabidopsis Fip1 protein interact with poly(A) polymerase (PAP). This
      domain also stimulates the activity of the PAP. Interestingly, this part of the
      Arabidopsis Fip1 interacts with Arabidopsis homologs of CstF77, CPSF30, CFIm-25,
      and PabN1. The interactions with CstF77, CPSF30, and CFIm-25 are reminiscent in
      various respects of similar interactions seen in yeast and mammals, although the
      part of the Arabidopsis Fip1 protein that participates in these interactions has
      no apparent counterpart in other eukaryotic Fip1 proteins. Interactions between
      Fip1 and PabN1 have not been reported in other systems; this may represent plant
      specific associations. The C-terminal 789 amino acids of the Arabidopsis Fip1
      protein were found to contain an RNA-binding domain; this domain correlated with
      an intact arginine-rich region and had a marked preference for poly(G) among the
      four homopolymers studied. These results indicate that the Arabidopsis Fip1, like
      its human counterpart, is an RNA-binding protein. Moreover, they provide
      conceptual links between PAP and several other Arabidopsis polyadenylation factor
      subunit homologs.

PMID- 16282319
TI  - G-protein-coupled OX1 orexin/hcrtr-1 hypocretin receptors induce caspase
      dependent and -independent cell death through p38 mitogen-/stress-activated
      protein kinase.
AB  - We have investigated the signaling of OX(1) receptors to cell death using Chinese
      hamster ovary cells as a model system. OX(1) receptor stimulation with orexin-A
      caused a delayed cell death independently of cytosolic Ca(2+) elevation. The
      classical mitogen-activated protein kinase (MAPK) pathways, ERK and p38, were
      strongly activated by orexin-A. p38 was essential for induction of cell death,
      whereas the ERK pathway appeared protective. A pathway often implicated in the
      p38-mediated cell death, activation of p53, did not mediate the cell death, as
      there was no stabilization of p53 or increase in p53-dependent transcriptional
      activity, and dominant-negative p53 constructs did not inhibit cell demise. Under
      basal conditions, orexin-A-induced cell death was associated with compact
      chromatin condensation and it required de novo gene transcription and protein
      synthesis, the classical hallmarks of programmed (apoptotic) cell death. However,
      though the pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-(O
      methyl)fluoromethyl ketone (Z-VAD-fmk) fully inhibited the caspase activity, it
      did not rescue the cells from orexin-A-induced death. In the presence of Z-VAD
      fmk, orexin-A-induced cell death was still dependent on p38 and de novo protein
      synthesis, but it no longer required gene transcription. Thus, caspase inhibition
      causes activation of alternative, gene transcription-independent death pathway.
      In summary, the present study points out mechanisms for orexin receptor-mediated
      cell death and adds to our general understanding of the role of G-protein-coupled
      receptor signaling in cell death by suggesting a pathway from G-protein-coupled
      receptors to cell death via p38 mitogen-/stress-activated protein kinase
      independent of p53 and caspase activation.

PMID- 16282321
TI  - Temporal profile of amyloid-beta (Abeta) oligomerization in an in vivo model of
      Alzheimer disease. A link between Abeta and tau pathology.
AB  - Accumulation of amyloid-beta (Abeta) is one of the earliest molecular events in
      Alzheimer disease (AD), whereas tau pathology is thought to be a later downstream
      event. It is now well established that Abeta exists as monomers, oligomers, and
      fibrils. To study the temporal profile of Abeta oligomer formation in vivo and to
      determine their interaction with tau pathology, we used the 3xTg-AD mice, which
      develop a progressive accumulation of plaques and tangles and cognitive
      impairments. We show that SDS-resistant Abeta oligomers accumulate in an age
      dependent fashion, and we present evidence to show that oligomerization of Abeta
      appears to first occur intraneuronally. Finally, we show that a single
      intrahippocampal injection of a specific oligomeric antibody is sufficient to
      clear Abeta pathology, and more importantly, tau pathology. Therefore, Abeta
      oligomers may play a role in the induction of tau pathology, making the
      interference of Abeta oligomerization a valid therapeutic target.

PMID- 16282320
TI  - HMA1, a new Cu-ATPase of the chloroplast envelope, is essential for growth under
      adverse light conditions.
AB  - Although ions play important roles in the cell and chloroplast metabolism, little
      is known about ion transport across the chloroplast envelope. Using a proteomic
      approach specifically targeted to the Arabidopsis chloroplast envelope, we have
      identified HMA1, which belongs to the metal-transporting P1B-type ATPases family.
      HMA1 is mainly expressed in green tissues, and we validated its chloroplast
      envelope localization. Yeast expression experiments demonstrated that HMA1 is
      involved in copper homeostasis and that deletion of its N-terminal His-domain
      partially affects the metal transport. Characterization of hma1 Arabidopsis
      mutants revealed a lower chloroplast copper content and a diminution of the total
      chloroplast superoxide dismutase activity. No effect was observed on the
      plastocyanin content in these lines. The hma1 insertional mutants grew like WT
      plants in standard condition but presented a photosensitivity phenotype under
      high light. Finally, direct biochemical ATPase assays performed on purified
      chloroplast envelope membranes showed that the ATPase activity of HMA1 is
      specifically stimulated by copper. Our results demonstrate that HMA1 offers an
      additional way to the previously characterized chloroplast envelope Cu-ATPase
      PAA1 to import copper in the chloroplast.

PMID- 16282322
TI  - A novel o-aminophenol oxidase responsible for formation of the phenoxazinone
      chromophore of grixazone.
AB  - Grixazone contains a phenoxazinone chromophore and is a secondary metabolite
      produced by Streptomyces griseus. In the grixazone biosynthesis gene cluster,
      griF (encoding a tyrosinase homolog) and griE (encoding a protein similar to
      copper chaperons for tyrosinases) are encoded. An expression study of GriE and
      GriF in Escherichia coli showed that GriE activated GriF by transferring copper
      ions to GriF, as has been observed for a Streptomyces melanogenesis system in
      which the MelC1 copper chaperon transfers copper ions to MelC2 tyrosinase. In
      contrast with tyrosinases, GriF showed no monophenolase activity, although it
      oxidized various o-aminophenols as preferable substrates rather than catechol
      type substrates. Deletion of the griEF locus on the chromosome resulted in
      accumulation of 3-amino-4-hydroxybenzaldehyde (3,4-AHBAL) and its acetylated
      compound, 3-acetylamino-4-hydroxybenzaldehyde. GriF oxidized 3,4-AHBAL to yield
      an o-quinone imine derivative, which was then non-enzymatically coupled with
      another molecule of the o-quinone imine to form a phenoxazinone. The coexistence
      of N-acetylcysteine in the in vitro oxidation of 3,4-AH-BAL by GriF resulted in
      the formation of grixazone A, suggesting that the -SH group of N-acetylcysteine
      is conjugated to the o-quinone imine formed from 3,4-AHBAL and that the conjugate
      is presumably coupled with another molecule of the o-quinone imine. GriF is thus
      a novel o-aminophenol oxidase that is responsible for the formation of the
      phenoxazinone chromophore in the grixazone biosynthetic pathway.

PMID- 16282324
TI  - rab7 activity affects epidermal growth factor:epidermal growth factor receptor
      degradation by regulating endocytic trafficking from the late endosome.
AB  - The epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine
      kinase family. Ligand (epidermal growth factor or EGF) binding to the EGFR
      results in the coordinated activation and integration of biochemical signaling
      events to mediate cell growth, migration, and differentiation. One mechanism the
      cell utilizes to orchestrate these events is ligand-mediated endocytosis through
      the canonical clathrin-mediated endocytic pathway. Identification of proteins
      that regulate the intracellular movement of the EGF.EGFR complex is an important
      first step in dissecting how specificity of EGFR signaling is conferred. We
      examined the role of the small molecular weight guanine nucleotide-binding
      protein (G-protein) rab7 as a regulator of the distal stages of the endocytic
      pathway. Through the transient expression of activating and inactivating mutants
      of rab7 in HeLa cells, we have determined that rab7 activity directly correlates
      with the rate of radiolabeled EGF and EGFR degradation. Furthermore, when
      inhibitory mutants of rab7 are expressed, the internalized EGF.EGFR complex
      accumulates in high-density endosomes that are characteristic of the late
      endocytic pathway. Thus, we conclude that rab7 regulates the endocytic
      trafficking of the EGF.EGFR complex by regulating its lysosomal degradation.

PMID- 16282323
TI  - Evidence that Ser87 of BimEL is phosphorylated by Akt and regulates BimEL
      apoptotic function.
AB  - Bim, the Bcl-2 interacting mediator of cell death, is a member of the BH3-only
      family of pro-apoptotic proteins. Recent studies have demonstrated that the
      apoptotic activity of Bim can be regulated through a post-translational mechanism
      whereby ERK phosphorylation serves as a signal for Bim ubiquitination and
      proteasomal degradation. In this report, we investigated the signaling pathways
      leading to Bim phosphorylation in Ba/F3 cells, an interleukin-3 (IL-3)-dependent
      B-cell line. IL-3 stimulation induced phosphorylation of Bim(EL), one of the
      predominant isoforms of Bim expressed in cells, at multiple sites, as evidenced
      by the formation of at least three to four bands by Western blotting that were
      sensitive to phosphatase digestion. The appearance of multiple, phosphorylated
      species of Bim(EL) correlated with Akt, and not ERK, activation. The PI3K
      inhibitor, LY294002, blocked IL-3-stimulated Akt activity and partially blocked
      Bim(EL) phosphorylation. In vitro kinase assays showed that recombinant Akt could
      directly phosphorylate a GST-Bim(EL) fusion protein and identified the Akt
      phosphorylation site in the Bim(EL) domain as Ser(87). Further, we demonstrated
      that cytokine stimulation promotes Bim(EL) binding to 14-3-3 proteins. Finally,
      we show that mutation of Ser(87) dramatically increases the apoptotic potency of
      Bim(EL). We propose that Ser(87) of Bim(EL) is an important regulatory site that
      is targeted by Akt to attenuate the pro-apoptotic function of Bim(EL), thereby
      promoting cell survival.

PMID- 16282326
TI  - Trypsin cleaves acid-sensing ion channel 1a in a domain that is critical for
      channel gating.
AB  - Acid-sensing ion channels (ASICs) are neuronal Na(+) channels that are members of
      the epithelial Na(+) channel/degenerin family and are transiently activated by
      extracellular acidification. ASICs in the central nervous system have a
      modulatory role in synaptic transmission and are involved in cell injury induced
      by acidosis. We have recently demonstrated that ASIC function is regulated by
      serine proteases. We provide here evidence that this regulation of ASIC function
      is tightly linked to channel cleavage. Trypsin cleaves ASIC1a with a similar time
      course as it changes ASIC1a function, whereas ASIC1b, whose function is not
      modified by trypsin, is not cleaved. Trypsin cleaves ASIC1a at Arg-145, in the N
      terminal part of the extracellular loop, between a highly conserved sequence and
      a sequence that is critical for ASIC1a inhibition by the venom of the tarantula
      Psalmopoeus cambridgei. This channel domain controls the inactivation kinetics
      and co-determines the pH dependence of ASIC gating. It undergoes a conformational
      change during inactivation, which renders the cleavage site inaccessible to
      trypsin in inactivated channels.

PMID- 16282325
TI  - Distinct BIR domains of cIAP1 mediate binding to and ubiquitination of tumor
      necrosis factor receptor-associated factor 2 and second mitochondrial activator
      of caspases.
AB  - Inhibitor of apoptosis proteins (IAPs) regulate apoptosis primarily by inhibiting
      caspase-family proteases. However, many IAPs also possess E3 ligase (ubiquitin
      protein isopeptide ligase) activities implicated in both caspase-dependent and 
      independent functions of these proteins. Here, we compared the structural
      features of cIAP1 responsible for its interactions with two known target
      proteins, TRAF2 and SMAC. The N-terminal (BIR1) and C-terminal (BIR3) BIR domains
      of cIAP1 were determined to be necessary and sufficient for binding TRAF2 and
      SMAC, respectively. Mutational analysis of the BIR1 and BIR3 domains identified
      critical residues required for TRAF2 and SMAC binding. Using these mutants, cIAP1
      mediated ubiquitination of TRAF2 and SMAC in vitro was determined to be
      correspondingly dependent on intact binding sites on BIR1 and BIR3. Because TRAF2
      regulates NF-kappaB activation, the effects of cIAP1 on TRAF2-mediated induction
      of NF-kappaB transcriptional activity were studied using reporter gene assays.
      Expression of a fragment of cIAP1 encompassing the three BIR domains (but not
      full-length cIAP1) greatly enhanced TRAF2-induced increases in NF-kappaB
      activity, providing a convenient assay for monitoring BIR-dependent effects of
      cIAP1 on TRAF2 in cells. BIR1 mutants of the BIR1-3 fragment of cIAP1 that failed
      to bind TRAF2 lost the ability to modulate NF-kappaB activity, demonstrating a
      requirement for BIR1-mediated interactions with TRAF2. Altogether, these findings
      demonstrate the modularity and diversification of BIR domains, showing that a
      single cIAP can direct its E3 ligase activity toward different substrates and can
      alter the cellular functions of different protein targets in accordance with
      differences in the specificity of individual BIR domains.

PMID- 16282327
TI  - Base flipping in nucleotide excision repair.
AB  - UvrB, the ultimate damage-binding protein in bacterial nucleotide excision repair
      is capable of binding a vast array of structurally unrelated lesions. A beta
      hairpin structure in the protein plays an important role in damage-specific
      binding. In this paper we have monitored DNA conformational alterations in the
      UvrB-DNA complex, using the fluorescent adenine analogue 2-aminopurine. We show
      that binding of UvrB to a DNA fragment with cholesterol damage moves the base
      adjacent to the lesion at the 3' side into an extrahelical position. This
      extrahelical base is not accessible for acrylamide quenching, suggesting that it
      inserts into a pocket of the UvrB protein. Also the base opposite this flipped
      base is extruded from the DNA helix. The degree of solvent exposure of both
      residues varies with the type of cofactor (ADP/ATP) bound by UvrB. Fluorescence
      of the base adjacent to the damage is higher when UvrB is in the ADP-bound
      configuration, but concomitantly this UvrB-DNA complex is less stable. In the ATP
      bound form the UvrB-DNA complex is very stable and in this configuration the base
      in the non-damaged strand is more exposed. Hairpin residue Tyr-95 is specifically
      involved in base flipping in the non-damaged strand. We present evidence that
      this conformational change in the non-damaged strand is important for 3' incision
      by UvrC.

PMID- 16282328
TI  - Role of transmembrane segment 10 in efflux mediated by the staphylococcal
      multidrug transport protein QacA.
AB  - The staphylococcal multidrug exporter QacA confers resistance to a wide range of
      structurally dissimilar monovalent and bivalent cationic antimicrobial compounds.
      To understand the functional importance of transmembrane segment 10, which is
      thought to be involved in substrate binding, cysteine-scanning mutagenesis was
      performed in which 35 amino acid residues in the putative transmembrane helix and
      its flanking regions were replaced in turn with cysteine. Solvent accessibility
      analysis of the introduced cysteine residues using fluorescein maleimide
      indicated that transmembrane segment 10 of QacA contains a 20-amino-acid
      hydrophobic core and may extend from Pro-309 to Ala-334. Phenotypic analysis and
      fluorimetric transport assays of these mutants showed that Gly-313 is important
      for the efflux of both monovalent and bivalent cationic substrates, whereas Asp
      323 is only important for the efflux of bivalent substrates and probably forms
      part of the bivalent substrate-binding site(s) together with Met-319.
      Furthermore, the effects of N-ethyl-maleimide treatment on ethidium and 4',6
      diamidino-2-phenylindole export mediated by the QacA mutants suggest that the
      face of transmembrane segment 10 that contains Asp-323 may also be close to the
      monovalent substrate-binding site(s), making this helix an integral component of
      the QacA multidrug-binding pocket.

PMID- 16282329
TI  - The forkhead transcription factor Foxo1 bridges the JNK pathway and the
      transcription factor PDX-1 through its intracellular translocation.
AB  - It has been shown that oxidative stress and activation of the c-Jun N-terminal
      kinase (JNK) pathway induce the nucleocytoplasmic translocation of the pancreatic
      transcription factor PDX-1, which leads to pancreatic beta-cell dysfunction. In
      this study, we have shown that the forkhead transcription factor Foxo1/FKHR plays
      a role as a mediator between the JNK pathway and PDX-1. Under oxidative stress
      conditions, Foxo1 changed its intracellular localization from the cytoplasm to
      the nucleus in the pancreatic beta-cell line HIT-T15. The overexpression of JNK
      also induced the nuclear localization of Foxo1, but in contrast, suppression of
      JNK reduced the oxidative stress-induced nuclear localization of Foxo1,
      suggesting the involvement of the JNK pathway in Foxo1 translocation. In
      addition, oxidative stress or activation of the JNK pathway decreased the
      activity of Akt in HIT cells, leading to the decreased phosphorylation of Foxo1
      following nuclear localization. Furthermore, adenovirus-mediated Foxo1
      overexpression reduced the nuclear expression of PDX-1, whereas repression of
      Foxo1 by Foxo1-specific small interfering RNA retained the nuclear expression of
      PDX-1 under oxidative stress conditions. Taken together, Foxo1 is involved in the
      nucleocytoplasmic translocation of PDX-1 by oxidative stress and the JNK pathway.

PMID- 16282330
TI  - Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase promoter by nuclear
      receptors liver receptor homologue-1 and small heterodimer partner: a mechanism
      for differential regulation of cholesterol synthesis and uptake.
AB  - Cholesterol homeostasis in mammals involves pathways for biosynthesis, cellular
      uptake, and hepatic conversion to bile acids. Key genes for all three pathways
      are regulated by negative feedback control. Uptake and biosynthesis are directly
      regulated by cholesterol through its inhibition of the proteolytic activation of
      the sterol regulatory element binding proteins. The conversion of cholesterol
      into bile acids in the liver is regulated through the bile acid-dependent
      induction of the negatively acting small heterodimer partner nuclear receptor. In
      this report, we have shown that the small heterodimer partner also directly
      regulates cholesterol biosynthesis through inhibition of 3-hydroxy-3
      methylglutaryl coenzyme A reductase but has no effect on low density lipoprotein
      receptor expression. This has significant metabolic significance, as it provides
      both a mechanism to independently regulate cholesterol synthesis from uptake (an
      essential regulatory feature known to occur in vivo) and a pathway for direct
      regulation of cholesterol biosynthesis by bile acids. This latter feature ensures
      that the early phase of bile acid synthesis (pre-cholesterol) is in metabolic
      communication with the later stages of the pathway to properly regulate whole
      pathway flux. This highlights an important regulatory feature that is shared with
      other key branched, multienzyme pathways, such as glycolysis, where pathway
      outflow through pyruvate kinase is regulated by the concentration of a key early
      intermediate, fructose 1,6-bisphosphate.

PMID- 16282331
TI  - PsbR, a missing link in the assembly of the oxygen-evolving complex of plant
      photosystem II.
AB  - The oxygen-evolving complex of eukaryotic photosystem II (PSII) consists of three
      extrinsic nuclear-encoded subunits, PsbO (33 kDa), PsbP (23 kDa), and PsbQ (17
      kDa). Additionally, the 10-kDa PsbR protein has been found in plant PSII and
      anticipated to play a role in water oxidation, yet the physiological significance
      of PsbR has remained obscure. Using the Arabidopsis psbR mutant, we showed that
      the light-saturated rate of oxygen evolution is strongly reduced in the absence
      of PsbR, particularly in low light-grown plants. Lack of PsbR also induced a
      reduction in the content of both the PsbP and the PsbQ proteins, and a near
      depletion of these proteins was observed under steady state low light conditions.
      This regulation occurred post-transcriptionally and likely involves a proteolytic
      degradation of the PsbP and PsbQ proteins in the absence of an assembly partner,
      proposed to be the PsbR protein. Stable assembly of PsbR in the PSII core complex
      was, in turn, shown to require a chloroplast-encoded intrinsic low molecular mass
      PSII subunit PsbJ. Our results provided evidence that PsbR is an important link
      in the PSII core complex for stable assembly of the oxygen-evolving complex
      protein PsbP, whereas the effects on the assembly of PsbQ are probably indirect.
      The physiological role of the PsbR, PsbP, and PsbQ proteins is discussed in light
      of their peculiar expression in response to growth light conditions.

PMID- 16282332
TI  - A splicing repressor domain in polypyrimidine tract-binding protein.
AB  - Polypyrimidine tract-binding protein (PTB) is an hnRNP with four RRM type
      domains. It plays roles as a repressive alternative splicing regulator of
      multilple target genes, as well as being involved in pre-mRNA 3' end processing,
      mRNA localization, stability, and internal ribosome entry site-mediated
      translation. Here we have used a tethered function assay, in which a fusion
      protein of PTB and the bacteriophage MS2 coat protein is recruited to a splicing
      regulatory site by binding to an artificially inserted MS2 binding site. Deletion
      mutations of PTB in this system allowed us to identify RRM2 and the following
      inter-RRM linker region as the minimal region of PTB that can act as splicing
      repressor domain when recruited to RNA. Splicing repression by the minimal
      repressor domain remained cell type-specific and dependent upon other defined
      regulatory elements in the alpha-tropomyosin test minigene. Our results highlight
      the fact that splicing repression by PTB can be uncoupled from the mode by which
      it binds to RNA.

PMID- 16282333
TI  - Implementation of a new policy results in a decrease of pressure ulcer frequency.
AB  - OBJECTIVE: To determine the effects of a new policy on the efficiency of pressure
      ulcer care. DESIGN: Series of 1-day pressure ulcer surveys before and after the
      implementation. SETTING: A 900-bed University Medical Centre in The Netherlands.
      PARTICIPANTS: On the days of the surveys, 657 patients were included before the
      implementation, 735 patients at 4 months after the implementation, and 755
      patients at 11 months after the implementation. INTERVENTION: Implementation of a
      hospital guideline for pressure ulcer care combined with the introduction of
      viscoelastic foam mattresses on the efficiency of the prevention and treatment of
      pressure ulcers. MAIN OUTCOME MEASURES: Comparisons before versus after the
      implementation were made regarding the care behaviour of nurses and the frequency
      of patients with pressure ulcer. RESULTS: Inadequate prevention decreased from 19
      to 4% after 4 months and to 6% after 11 months (P < 0.001), and inadequate
      treatment decreased from 60 to 31% (P = 0.005). Excluding the use of mattresses
      as a positive indicator for care behaviour, we found no significant increase in
      adequate care to prevent pressure ulcers. Also, in adequate treatment activities,
      we found no significant difference. Overall, we found a significant decrease in
      hospital-acquired pressure ulcer frequency from 18 to 13% (P = 0.003) after 4
      months and 11% (P < 0.001) after 11 months. CONCLUSION: The number of pressure
      ulcer patients in hospital can successfully be reduced. General measures such as
      the introduction of adequate mattresses and guidelines for prevention and
      treatment are promising tools in this respect.

PMID- 16282334
TI  - Patient-reported service quality on a medicine unit.
AB  - PURPOSE: Service quality, defined as patients' self-reported experience of care,
      is used as a metric for evaluating quality. Most studies rely on retrospective
      consumer surveys rather then more intensive data collection methods, possibly
      underestimating the incidence of service quality incidents. SUBJECTS AND METHODS:
      The objective of the study was to characterize patient-reported service quality
      deficiencies on a general medicine unit. We studied a cohort of 228 adult
      inpatients at a Boston teaching hospital. Investigators reviewed medical records
      and interviewed patients during the hospitalization and by telephone after
      discharge. Physician investigators classified patients' incident reports. We
      calculated the rate of service incidents, characterized incident types, and used
      multivariable Poisson and logistic regression models to examine factors
      associated with patient reporting and overall rating of the hospitalization.
      RESULTS: Eighty-eight (38.6%) of 228 patients experienced 157 service quality
      incidents during the admission, for a rate of 68.9 incidents per 100 admissions.
      The most common service quality problems involved waits and delays (n = 45),
      problems with communication between staff and patients (n = 36), and
      environmental issues and amenities (n = 35). In the multivariable analysis, men
      (IRR 1.6, 95% CI 1.1-2.2), patients covered by hospitalists (1.5, 1.1-2.2), and
      patients with more medication allergies (1.1 per allergy, 1.1-1.2) reported more
      service incidents; patients with Medicaid or free care reported fewer (0.5, 0.3
      0.9). Patients with service quality incidents were more likely to describe the
      hospitalization as other than excellent (adjusted OR 1.8 per incident, 95% CI 1.3
      2.5). CONCLUSION: Service quality deficiencies are common among medical
      inpatients, and are strongly associated with patients' dissatisfaction with the
      hospitalization.

PMID- 16282335
TI  - A descriptive study of the implementation of the EFQM excellence model and
      underlying tools in the Basque Health Service.
AB  - OBJECTIVE: To describe the implementation of the European Foundation for Quality
      Management (EFQM) excellence model as a common framework for quality management
      in a regional health care service. DESIGN: Prospective, descriptive observational
      study. SETTING: Thirty-one organizations (hospitals, primary care organizations,
      mental health institutions, and emergency services) of the Basque Health Service
      (serving a population of 2200000 inhabitants) in Basque Country, Spain. METHODS:
      Since 1995, the experiences with the EFQM excellence model were initiated by
      training, the design of quality tools and application guidelines, and actions
      related to criteria of the EFQM model. RESULTS: Four assessment cycles in which
      most of the organizations have participated were completed. Scores for most of
      the criteria improved, particularly in 'processes'. The overall patients'
      satisfaction was higher than 89% in all settings, in most of the cases higher
      than 95%. Ten organizations (32%) exceeded 400 points in an external evaluation
      with the EFQM excellence model, and 2 (6%) 500 points. Eighty-three percent of
      hospitals have some ISO-certified areas of activity. In the primary care setting,
      40% of people were attended in a certified center. CONCLUSIONS: Stimulating
      actions towards quality have resulted in progressive implementation of the EFQM
      model, this approach being possibly related to positive evolution of some
      outcomes. Key factors identified have been pursuing the objective of total
      quality management during several years and the assignment of the resources for
      training and implementation of quality systems.

PMID- 16282336
TI  - Eicosapentaenoic acid ameliorates diabetic nephropathy of type 2 diabetic KKAy/Ta
      mice: involvement of MCP-1 suppression and decreased ERK1/2 and p38
      phosphorylation.
AB  - BACKGROUND: Previous studies reported that eicosapentaenoic acid (EPA) was
      effective against any renal diseases including diabetic nephropathy. Monocyte
      chemoattractant protein-1 (MCP-1) is a regulating macrophage recruitment protein,
      which is up-regulated in patients with diabetic nephropathy. The objectives of
      the present study were to evaluate the effects of EPA including renal MCP-1
      expression in diabetic KKAy/Ta mice, MCP-1 production and signal transduction in
      mouse mesangial cells (MMCs). METHODS: KKAy/Ta mice were injected with EPA ethyl
      ester (1 g/kg/day) intraperitoneally. Immunohistochemical staining of MCP-1,
      F4/80, phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2) and phospho
      p38 in the renal sections were performed. EPA or specific inhibitors were
      incorporated in MMCs, and the levels of supernatant MCP-1 were measured. The
      effect of EPA on ERK1/2, c-jun NH2-terminal kinase (JNK), p38 or phosphoinositide
      3-kinase (PI3K) activity in MMCs was examined using Western blot. RESULTS: EPA
      decreased the levels of serum triglycerides, leptin, urinary albumin and MCP-1,
      and improved glucose intolerance, mesangial matrix accumulation and
      tubulointerstitial fibrosis in KKAy/Ta mice. Immunohistochemical staining of MCP
      1 and F4/80 in the glomeruli and tubulointerstitial regions was decreased in the
      EPA-treated group. EPA and specific inhibitors of ERK1/2, JNK and PI3K decreased
      levels of MCP-1 in MMCs. EPA suppressed phosphorylation of ERK1/2 and p38 in
      MMCs, and decreased p-ERK positive cells in glomeruli of KKAy/Ta mice.
      CONCLUSIONS: EPA ameliorates diabetic nephropathy of type 2 diabetic KKAy/Ta
      mice. We propose that the observed down-regulation of MCP-1 is critically
      involved in the beneficial effect of EPA, probably in concert with improvement of
      other clinical parameters.

PMID- 16282337
TI  - Notch1 mutations are important for leukemic transformation in murine models of
      precursor-T leukemia/lymphoma.
AB  - NOTCH1 is frequently mutated in human precursor T-cell lymphoblastic
      leukemia/lymphoma (pre-T LBL). In the current study, we found that 13 of 19 cell
      lines and 29 of 49 primary tumors from SCL/LMO1, OLIG2/LMO1, OLIG2, LMO1,
      NUP98/HOXD13, and p27(-/-)/SMAD3(+/-) mice had Notch1 mutations in either the
      heterodimerization (HD) or the glutamic acid/serine/threonine (PEST) domain but
      not both. Thymocytes from clinically healthy SCL/LMO1 mice aged 5 weeks did not
      have Notch1 mutations, whereas thymocytes from clinically healthy SCL/LMO1 mice
      aged 8 to 12 weeks did have Notch1 mutations and formed tumors upon
      transplantation into nude mice. Remarkably, all of the HD domain mutations that
      we identified were single-base substitutions, whereas all of the PEST domain
      mutations were insertions or deletions, half of which mapped to 1 of 2 mutational
      "hot spots." Taken together, these findings indicate that Notch1 mutations are
      very frequent events that are acquired relatively early in the process of
      leukemic transformation and are important for leukemic cell growth.

PMID- 16282338
TI  - Transforming growth factor-beta2 is involved in quantitative genetic variation in
      thymic involution.
AB  - The mechanisms regulating thymic involution are unclear. In inbred mouse strains
      the rate of thymic involution and the function of the hematopoietic stem cell
      (HSC) compartment are subject to quantitative genetic variation. We have shown
      previously that transforming growth factor-beta2 (TGF-beta2) is a genetically
      determined positive regulator of HSCs. Here, we demonstrate that genetic
      variation in the rate of thymic involution correlates with genetic variation in
      the responsiveness of hematopoietic stem and progenitor cells to TGF-beta2.
      Corroborating these correlations, thymic cellularity and peripheral naive T-cell
      frequency were higher in old Tgfb2+/- mice than in wild-type littermates. The
      frequency of early T-cell precursors was increased in Tgfb2+/- mice, suggesting
      that TGF-beta2 affects the earliest stages of T-cell development in old mice.
      Reciprocal transplantation experiments indicated that TGF-beta2 expressed both in
      the (micro)environment and in the hematopoietic system can accelerate thymic
      involution; however, the age of the stem cells appeared irrelevant. Thus,
      although thymic involution is largely determined by the aged environment, TGF
      beta2 plays a major modulatory role that is subject to genetic variation and is
      possibly mediated through its regulatory effects on early hematopoiesis.

PMID- 16282339
TI  - Long-term acyclovir for prevention of varicella zoster virus disease after
      allogeneic hematopoietic cell transplantation--a randomized double-blind placebo
      controlled study.
AB  - Varicella-zoster virus (VZV) disease occurs in 30% of allogeneic hematopoietic
      cell transplant recipients who had a history of VZV infection. A safe and
      effective prevention strategy has not been established. In a double-blind
      controlled trial, 77 hematopoietic cell transplant recipients at risk for VZV
      reactivation were randomized to acyclovir 800 mg twice daily or placebo given
      from 1 to 2 months until 1 year after transplantation. VZV disease at 1 year was
      the primary end point; VZV disease after discontinuation of prophylaxis, VZV
      specific T-cell immunity, herpes simplex virus (HSV) infection, cytomegalovirus
      (CMV) disease, survival, and safety were secondary end points. Acyclovir
      significantly reduced VZV infections at 1 year after transplantation (HR, 0.16;
      95% CI, 0.035-0.74; P = .006). In the post-intervention observation period, this
      difference was not statistically significant (2 years: HR, 0.52; 95% CI, 0.21
      1.3; 5 years: HR, 0.76; 95% CI, 0.36-1.6). There was no statistically significant
      difference in reconstitution of VZV-specific T-helper cell responses, HSV
      infections, CMV disease, chronic graft-versus-host disease, and overall survival
      between the groups. Acyclovir was well tolerated. Post-study VZV disease
      predominantly occurred in patients with continued need for systemic
      immunosuppression. In conclusion, acyclovir effectively and safely prevents VZV
      disease during the first year after hematopoietic cell transplantation. Periods
      of prophylaxis longer than 12 months may be beneficial for those hematopoietic
      cell transplant recipients on continued immune suppression.

PMID- 16282340
TI  - Drug-resistant T-lymphoid tumors undergo apoptosis selectively in response to an
      antimicrotubule agent, EM011.
AB  - We have shown previously that EM011, a synthetic compound, binds tubulin with a
      higher affinity than the founding compound, noscapine, without changing total
      microtubule polymer mass. Now we show that EM011 is potently effective against
      vinblastine-resistant human lymphoblastoid line CEM/VLB100 and its parental
      vinblastine-sensitive line CEM. The cytotoxicity is mediated by cell cycle arrest
      at G2/M phase and subsequent apoptosis, as indicated by altered plasma membrane
      asymmetry, loss of mitochondrial transmembrane potential, activation of caspase
      3, and increased DNA fragmentation. Furthermore, oral EM011 treatment of nude
      mice bearing human lymphoma xenografts results in pronounced tumor regression by
      triggering apoptosis and significantly lengthens the survival time of mice. EM011
      treatment does not have obvious side effects in tissues with frequently dividing
      cells, such as the spleen and duodenum. In addition, EM011 does not show any
      toxicity in the liver, lung, heart, brain, and sciatic nerve. More importantly,
      EM011 does not affect hematopoiesis as determined by complete blood count
      profiles. These findings suggest that EM011 may be a safe and effective
      chemotherapeutic agent for oral treatment of drug-resistant human lymphomas.

PMID- 16282341
TI  - Analysis of transgene-specific immune responses that limit the in vivo
      persistence of adoptively transferred HSV-TK-modified donor T cells after
      allogeneic hematopoietic cell transplantation.
AB  - The introduction of an inducible suicide gene such as the herpes simplex virus
      thymidine kinase (HSV-TK) might allow exploitation of the antitumor activity of
      donor T cells after allogeneic hematopoietic cell transplantation (HCT) without
      graft versus host disease. However, HSV-TK is foreign, and immune responses to
      gene-modified T cells could lead to their premature elimination. We show that
      after the infusion of HSV-TK-modified donor T cells to HCT recipients, CD8+ and
      CD4+ T-cell responses to HSV-TK are rapidly induced and coincide with the
      disappearance of transferred cells. Cytokine flow cytometry using an overlapping
      panel of HSV-TK peptides allowed rapid detection and quantitation of HSV-TK
      specific T cells in the blood and identified multiple immunogenic epitopes.
      Repeated infusion of modified T cells boosted the induced HSV-TK-specific T
      cells, which persisted as memory cells. These studies demonstrate the need for
      nonimmunogenic suicide genes and identify a strategy for detection of CD4+ and
      CD8+ T-cell responses to transgene products that should be generally applicable
      to monitoring patients on gene therapy trials. The potency of gene-modified T
      cells to elicit robust and durable immune responses imply this approach might be
      used for vaccination to elicit T-cell responses to viral or tumor antigens.

PMID- 16282342
TI  - Nitric oxide generation from hydroxyurea: significance and implications for
      leukemogenesis in the management of myeloproliferative disorders.
AB  - The use of myelosuppressive agents to reduce the risk of thrombosis in patients
      with polycythemia vera (PV) and essential thrombocythemia (ET) has been
      associated with an increased risk of transformation to acute myeloid leukemia
      (AML). Whereas chlorambucil, busulfan, and radiophosphorus (32P) have been
      demonstrated to increase the risk of transformation, the leukemogenic potential
      of hydroxyurea (HU) continues to be a matter of debate. Clinical studies have
      suggested that HU may cause a small increase in the risk of AML, but it has
      proven difficult to establish whether AML is actually caused by HU or arises
      during the natural progression of PV and ET. Reports that HU undergoes metabolic
      activation to species that induce mutation appear to support the notion that it
      is leukemogenic. Here, we suggest that the ability of HU to induce mutation in
      cell culture studies results from the generation of nitrogen dioxide via the
      autoxidation of nitric oxide, a product of HU metabolism. However, we argue that
      autoxidation would not occur in vivo, leading to the conclusion that generation
      of the mutagen nitrogen dioxide is peculiar to cell culture systems and has
      little relevance to the use of HU in the management of PV and ET.

PMID- 16282343
TI  - Mammalian target of rapamycin (mTOR) regulates both proliferation of
      megakaryocyte progenitors and late stages of megakaryocyte differentiation.
AB  - A major determinant in platelet production is the megakaryocyte (MK) size that is
      regulated both by ploidization and the increase in cytoplasmic volume at the end
      of maturation. Here we investigated the involvement of the mammalian target of
      rapamycin (mTOR) pathway in the regulation of megakaryopoiesis. We show that
      phosphorylation of mTOR, p70S6K1, and 4E-BP1 was diminished in thrombopoietin
      cultured human MKs after rapamycin treatment. Rapamycin induced an inhibition in
      the G1/S transition and a decrease in the mean MK ploidy via a diminution of p21
      and cyclin D3 occurring at a transcriptional level. Both cycling (2N/4N) and
      polyploid (8N/16N) MKs were reduced in size, with a size reduction slightly more
      pronounced in mature polyploid MKs than in immature ones. Rapamycin also induced
      a delay in the expression of MK markers and prevented the generation of
      proplatelet MKs. Additional experiments performed in vitro with MKs from mutant
      mice showed that the decrease in mean ploidy level and the delay in MK
      differentiation in the presence of rapamycin were less pronounced in CdknIa (p21)
      /- MKs than in CdknIa (p21)+/+ MKs. These findings indicate that the mTOR pathway
      plays an important role during megakaryopoiesis by regulating ploidy, cell size,
      and maturation, in part by regulating p21 and cyclin D3.

PMID- 16282344
TI  - Fas ligand is localized to membrane rafts, where it displays increased cell death
      inducing activity.
AB  - Fas ligand (FasL), a member of the TNF protein family, potently induces cell
      death by activating its matching receptor Fas. Fas-mediated killing plays a
      critical role in naturally and pathologically occurring cell death, including
      development and homeostasis of the immune system. In addition to its receptor
      interacting and cell death-inducing extracellular domain, FasL has a well
      conserved intracellular portion with a proline-rich SH3 domain-binding site
      probably involved in non-apoptotic functions. We report here that, as with the
      Fas receptor, a fraction of FasL is constitutively localized in rafts. These
      dynamic membrane microdomains, enriched in sphingolipids and cholesterol, are
      important for cell signaling and trafficking processes. We show that FasL is
      partially localized in rafts and that increased amounts of FasL are found in
      rafts after efficient FasL/Fas receptor interactions. Raft disorganization after
      cholesterol oxidase treatment and deletions within the intracellular FasL domain
      diminish raft partitioning and, most important, lead to decreased FasL killing.
      We conclude that FasL is recruited into lipid rafts for maximum Fas receptor
      contact and cell death-inducing potency. These findings raise the possibility
      that certain pathologic conditions may be treated by altering the cell death
      inducing capability of FasL with drugs affecting its raft localization.

PMID- 16282345
TI  - Reconstitution of the functional human hematopoietic microenvironment derived
      from human mesenchymal stem cells in the murine bone marrow compartment.
AB  - Hematopoiesis is maintained by specific interactions between both hematopoietic
      and nonhematopoietic cells. Whereas hematopoietic stem cells (HSCs) have been
      extensively studied both in vitro and in vivo, little is known about the in vivo
      characteristics of stem cells of the nonhematopoietic component, known as
      mesenchymal stem cells (MSCs). Here we have visualized and characterized human
      MSCs in vivo following intramedullary transplantation of enhanced green
      fluorescent protein-marked human MSCs (eGFP-MSCs) into the bone marrow (BM) of
      nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Between 4 to
      10 weeks after transplantation, eGFP-MSCs that engrafted in murine BM integrated
      into the hematopoietic microenvironment (HME) of the host mouse. They
      differentiated into pericytes, myofibroblasts, BM stromal cells, osteocytes in
      bone, bone-lining osteoblasts, and endothelial cells, which constituted the
      functional components of the BM HME. The presence of human MSCs in murine BM
      resulted in an increase in functionally and phenotypically primitive human
      hematopoietic cells. Human MSC-derived cells that reconstituted the HME appeared
      to contribute to the maintenance of human hematopoiesis by actively interacting
      with primitive human hematopoietic cells.

PMID- 16282346
TI  - Bortezomib induces selective depletion of alloreactive T lymphocytes and
      decreases the production of Th1 cytokines.
AB  - We explored the ability of the proteasome inhibitor bortezomib, which prevents
      nuclear factor kappaB (NF-kappaB) activation, to block T-cell activation,
      proliferation, and survival within alloreactive compared with resting T cells.
      For this purpose, T cells were stimulated with PHA, alphaCD3/alphaCD28, or
      allogeneic dendritic cells or through mixed lymphocyte cultures. NF-kappaB
      expression increased in activated T lymphocytes compared with resting T cells. Of
      interest, the higher the NF-kappaB expression, the more intense the proliferative
      blockade induced by bortezomib. Moreover, after mixed lymphocyte reaction (MLR)
      cultures, alloreactive T cells were 2 logs more sensitive to bortezomib-induced
      apoptosis than the resting T-cell counterpart. This effect was due to a selective
      induction of apoptosis among activated T cells that was related to caspase
      activation and cleavage of the antiapoptotic bcl-2 protein and was partially
      abolished by the addition of the pancaspase inhibitor Z-VAD-FMK. In addition,
      after secondary MLR, the number of activated T cells was significantly reduced
      among T lymphocytes previously cultured with bortezomib when cells from the same
      donor were used as stimulating cells. By contrast, when third-party donor cells
      were used as stimulating cells, no significant differences were observed between
      T lymphocytes previously exposed or not to the drug, indicating a highly specific
      depletion of T lymphocytes alloreactive against primary donor antigens. The
      addition of bortezomib decreased not only the proliferation and viability of
      activated T lymphocytes but also the levels of IFNgamma and IL-2, which were
      significantly decreased among activated T cells cultured with bortezomib at doses
      ranging from 10 to 100 nM. In conclusion, at concentrations reached in the
      clinical setting, bortezomib induces selective apoptosis and decreases Th1
      response among alloreactive T lymphocytes while it barely affects unstimulated T
      cells. These results establish the basis for the clinical use of bortezomib in
      the management of graft-versus-host disease (GVHD).

PMID- 16282347
TI  - Human leukocyte antigen (HLA) DR15 is associated with reduced incidence of acute
      GVHD in HLA-matched allogeneic transplantation but does not impact chronic GVHD
      incidence.
AB  - The DR15 allele at the HLA DRB1 locus is a marker for immune-mediated bone marrow
      failure syndromes. We hypothesized that HLA DR15 plays a role in T-cell
      interactions with hematopoiesis and investigated the role of HLA DR15 on graft
      versus-host disease (GVHD) and graft-versus-leukemia effects in HLA-matched
      allogeneic blood or marrow transplantation (BMT) performed for myeloid
      malignancies. We performed a retrospective analysis of 119 consecutive related
      and 48 consecutive unrelated allogeneic BMT for myeloid malignancies treated
      between 1991 and 2005 to investigate the influence of HLA DR15 on overall
      survival (OS), progression-free survival (PFS), and incidence of grades II to IV
      acute GVHD. HLA DR15 was determined by either molecular (n = 108) or serologic (n
      = 59) methods. The incidence of HLA DR15 was similar to the general white
      population (35/167 = 21%). There were no significant differences in
      transplantation characteristics between the HLA DR15-positive and -negative
      groups. There was no significant difference in chronic GVHD, OS, or PFS between
      the HLA DR15-positive versus-negative groups in any disease or donor relation
      subgroups. The HLA DR15-positive group experienced a significantly lower
      incidence of acute GVHD grades II to IV: 23% versus 42% (P = .041). These results
      suggest that HLA DR15 reduces the risk of acute GVHD.

PMID- 16282348
TI  - Functional analysis of mutations in the kinase domain of the TGF-beta receptor
      ALK1 reveals different mechanisms for induction of hereditary hemorrhagic
      telangiectasia.
AB  - Genetic studies in mouse and zebrafish have established the importance of activin
      receptor-like kinase 1 (ALK1) in formation and remodeling of blood vessels.
      Single-allele mutations in the ALK1 gene have been linked to the human type 2
      hereditary hemorrhagic telangiectasia (HHT2). However, how these ALK1 mutations
      contribute to this disorder remains unclear. To explore the mechanism underlying
      effect of the HHT-related ALK1 mutations on receptor activity, we generated 11
      such mutants and investigated their signaling activities using reporter assay in
      mammalian cells and examined their effect on zebrafish embryogenesis. Here we
      show that some of the HHT2-related mutations generate a dominant-negative effect
      whereas the others give rise to a null phenotype via loss of protein expression
      or receptor activity. These data indicate that loss-of-function mutations in a
      single allele of the ALK1 locus are sufficient to contribute to defects in
      maintaining endothelial integrity.

PMID- 16282349
TI  - G-CSF induced reactive oxygen species involves Lyn-PI3-kinase-Akt and contributes
      to myeloid cell growth.
AB  - Granulocyte colony-stimulating factor (G-CSF) drives the production, survival,
      differentiation, and inflammatory functions of granulocytes. Reactive oxygen
      species (ROSs) provide a major thrust of the inflammatory response, though
      excessive ROSs may be deleterious. G-CSF stimulation showed a time- and dose
      dependent increase in ROS production, correlating with activation of Lyn and Akt.
      Inhibition of Lyn, PI3-kinase, and Akt abrogated G-CSF-induced ROS production.
      This was also blocked by DPI, a specific inhibitor of NADPH oxidase. Following G
      CSF stimulation, neutrophils from Lyn-/- mice produced less ROSs than wild-type
      littermates. G-CSF induced both serine phosphorylation and membrane translocation
      of p47phox, a subunit of NADPH oxidase. Because patients with a truncated G-CSF
      receptor have a high risk of developing acute myeloid leukemia (AML), we
      hypothesized that dysregulation of ROSs contributes to leukemogenesis. Cells
      expressing the truncated G-CSF receptor produced more ROSs than those with the
      full-length receptor. G-CSF-induced ROS production was enhanced in bone marrow
      derived neutrophils expressing G-CSFRdelta715, a truncated receptor. The
      antioxidant N-acetyl-L-cysteine diminished G-CSF-induced ROS production and cell
      proliferation by inhibiting Akt activation. These data suggest that the G-CSF
      induced Lyn-PI3K-Akt pathway drives ROS production. One beneficial effect of
      therapeutic targeting of Lyn-PI3K-kinase-Akt cascade is abrogating ROS
      production.

PMID- 16282350
TI  - Repetitive activation of hypothalamic G protein-coupled receptor 54 with
      intravenous pulses of kisspeptin in the juvenile monkey (Macaca mulatta) elicits
      a sustained train of gonadotropin-releasing hormone discharges.
AB  - The purpose of the present study was to further examine the hypothesis that
      activation of G protein-coupled receptor 54 (GPR54) signaling at the end of the
      juvenile phase of primate development is responsible for initiation of gonadarche
      and the onset of puberty. Accordingly, we determined whether repetitive iv
      administration of the GPR54 receptor agonist kisspeptin-10 (2 microg as a brief 1
      min infusion once every hour for 48 h) to the juvenile male rhesus monkey would
      prematurely elicit sustained, pulsatile release of hypothalamic GnRH, the
      neuroendocrine trigger for gonadarche. GnRH release was monitored indirectly by
      measuring LH secretion from the in situ pituitary, the GnRH responsiveness of
      which had been heightened before the experiment with an intermittent iv infusion
      of synthetic GnRH. Agonadal animals (n = 4) were employed to eliminate any
      confounding and secondary effects of changing feedback signals from the testis.
      The first brief infusion of kisspeptin-10 evoked an LH discharge that mimicked
      those produced by GnRH priming, and this was followed by a train of similar LH
      discharges in response to hourly activation of GPR54 by repetitive kisspeptin-10
      administration. Concomitant treatment with a GnRH receptor antagonist, acyline,
      abolished kisspeptin-10-induced LH release. Repetitive kisspeptin-10
      administration also provided a GnRH-dependent signal to FSH secretion. These
      findings are consistent with the notion that, in primates, the transition from
      the juvenile (attenuated GnRH release) to pubertal (robust GnRH release) state is
      controlled by activation of GPR54 resulting from increased expression of
      hypothalamic KiSS-1 and release of kisspeptin in this region of the brain.

PMID- 16282351
TI  - Activin A and inhibin A differentially regulate human uterine matrix
      metalloproteinases: potential interactions during decidualization and trophoblast
      invasion.
AB  - Embryo implantation and trophoblast invasion are tightly regulated processes,
      involving sophisticated communication between maternal decidual and fetal
      trophoblast cells. Decidualization is a prerequisite for successful implantation
      and is promoted by a number of paracrine agents, including activin A. To
      understand the downstream mechanisms of activin-promoted decidualization, the
      effects of activin on matrix metalloproteinases (MMPs) (important mediators of
      decidualization) were investigated. Activin A stimulated endometrial production
      of proMMPs-2, -3, -7, -9, and active MMP-2. In contrast, inhibin A was a potent
      inhibitor of proMMP-2, and antagonized the effect of activin on MMPs. Activin is
      up-regulated with decidualization, and MMPs-2, -3, and -9 increase in parallel.
      Furthermore, proMMP-2 production is stimulated when decidualization is
      accelerated with activin, and suppressed when activin is neutralized, attenuating
      decidualization. These data support that activin A promotes decidualization
      through up-regulating MMPs. Previous in vitro evidence proposes further roles for
      activin and MMPs in promoting trophoblast invasion; therefore, we examined their
      interrelationships in early human implantation sites. MMPs-7 and -9 were produced
      by static cytotrophoblast subpopulations, whereas MMP-2 was strikingly up
      regulated in invasive extravillous cytotrophoblasts (EVT). Maternal decidua is
      the primary source of activin, where a role in stimulating MMP-2 in iEVTs can be
      envisaged. Inhibin was absent from cytotrophoblast populations, except for a
      dramatic up-regulation in endovascular EVT plugs, coinciding with a down
      regulation of MMP-2. This suggests that inhibin may have a role in the cessation
      of vascular invasion. These data support that activin, via effects on MMPs, is an
      important factor in the maternal-fetal dialog regulating implantation.

PMID- 16282352
TI  - Hypoxia-inducible factor-1alpha expression in human endometrium and its
      regulation by prostaglandin E-series prostanoid receptor 2 (EP2).
AB  - The menstrual cycle is a complex interaction of sex steroids, prostanoids, and
      cytokines that lead to coordinated tissue degradation, regeneration and repair.
      The transcription factor hypoxia-inducible factor (HIF-1) plays critical roles in
      cellular responses to hypoxia, the generation of an inflammatory response and
      vasculogenesis through transcriptional activation of angiogenic genes. We
      hypothesize that HIF-1 is expressed in human endometrium and that locally
      synthesized prostaglandins (PGE2 and PGF(2alpha)) regulate HIF-1 activity. Here
      we demonstrate that PGE2 up-regulates HIF-1alpha mRNA and protein via the E
      series prostanoid receptor 2 (EP2), and this up-regulation is dependent on
      epidermal growth factor receptor kinase activity. We show the tight temporal
      spatial confinement of HIF-1alpha protein expression in endometrium across the
      cycle. HIF-1alpha is expressed exclusively during the secretory and menstrual
      phases. Protein expression is maximal at progesterone withdrawal during the late
      secretory and menstrual phase. HIF-1alpha protein colocalizes with prostaglandin
      EP2 receptor in glandular cells. In contrast, HIF-1beta/aryl receptor nuclear
      translocator 1 expression occurs throughout the cycle but is maximal in glandular
      cells during the proliferative phase. This provides evidence for a role for HIF-1
      in the menstrual cycle and demonstrates that HIF-1 activation in human
      endometrium may occur via a PGE2-regulated pathway and provides a coordinated
      pathway from progesterone withdrawal through to angiogenic gene expression via
      HIF-1.

PMID- 16282353
TI  - Role of peroxisome proliferator-activated receptor-gamma coactivator-1alpha in
      the transcriptional regulation of the human uncoupling protein 2 gene in INS-1E
      cells.
AB  - A role of uncoupling protein 2 (UCP2) as negative modulator of insulin secretion
      has been suggested, but the transcriptional pathways regulating beta-cell UCP2
      gene expression have been established in rodents only. We show here that the
      underlying sequence motifs are not conserved in the human gene and provide
      evidence for regulatory mechanisms involving the transcriptional cofactor
      peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC
      1alpha). PGC-1alpha potentiates thyroid hormone (T(3))-mediated transcriptional
      activation of the human UCP2 gene in INS-1E cells. Two thyroid hormone response
      elements (TREs) located at -322/-317 (TRE1) and -170/-165 (TRE2) were identified,
      and mutation of either TRE1 or TRE2 abrogated the stimulatory effect of T(3)
      treatment. Furthermore, two E-box motifs at -911/-906 (E1) and -743/-738 (E2) are
      involved in the regulation of UCP2 gene expression by sterol regulatory element
      binding protein isoforms (SREBP)-1a, -1c, and -2. Mutational analysis revealed
      that the presence of either E1 or E2 is sufficient to mediate activation of UCP2
      gene transcription by nuclear active SREBPs. PGC-1alpha coactivates liver X
      receptor-mediated expression of SREBP-1c as well as dexamethasone-stimulated
      SREBP-2 expression in INS-1E cells. These transcriptional responses are
      antagonized by orphan nuclear receptor short heterodimer partner overexpression,
      which might explain its positive effects on glucose-stimulated insulin secretion
      in beta-cells overexpressing UCP2. We also provide evidence that despite a lack
      of sequence homology within the regulatory region, the principal mechanisms
      regulating UCP2 gene expression are similar in rats and humans, being consistent
      with a role for UCP2 as a modulator of insulin secretion in humans.

PMID- 16282355
TI  - Effects of cytokines on gonadotropin-releasing hormone (GnRH) gene expression in
      primary hypothalamic neurons and in GnRH neurons immortalized conditionally.
AB  - Various cytokines produced during the immune reaction can modulate the
      neuroendocrine reproductive axis, probably by inducing changes in the activity of
      hypothalamic GnRH neurons. However, the precise cellular and molecular effects of
      cytokines on these neurons have not been reported yet. To gain a better insight
      into these regulations, we first examined the pattern of expression of cytokine
      receptors in a novel neuronal cell line expressing GnRH (Gnv-4 cells). Among
      others, gp130 is expressed in Gnv-4 cells, together with the ligand receptor
      subunits specific for IL-6 as well as oncostatin M (OSM). Consistent with the
      latter observation, we show that OSM stimulates the expression of the immediate
      early genes c-fos and early growth response-1 in Gnv-4 cells, an effect dependent
      upon the activation of the MAPK Erk1/2 intracellular signaling pathway.
      Functional studies performed in parallel in Gnv-4 cells and in primary
      hypothalamic neuronal cell cultures show that OSM, although devoid of any effect
      of its own on GnRH gene expression, can inhibit dose-dependently the stimulation
      of GnRH expression by N-methyl-d-aspartic acid. In conclusion, these data
      demonstrate that a GnRH-expressing neuronal cell line can be modulated in vitro
      by cytokines implicated in the regulation of the reproductive axis. Moreover,
      they provide the first evidence of an involvement of OSM in these regulations.

PMID- 16282354
TI  - The role of leptin in the development of the cerebral cortex in mouse embryos.
AB  - Leptin is detected in the sera, and leptin receptors are expressed in the
      cerebrum of mouse embryos, suggesting that leptin plays a role in cerebral
      development. Compared with the wild type, leptin-deficient (ob/ob) mice had fewer
      cells at embryonic day (E) 16 and E18 and had fewer 5-bromo-2'-deoxyuridine(+)
      cells at E14 and E16 in the neuroepithelium. Intracerebroventricular leptin
      injection in E14 ob/ob embryos increased the number of neuroepithelium cells at
      E16. In cultured neurosphere cells, leptin treatment increased Hes1 mRNA
      expression and maintained neural progenitors. Astrocyte differentiation was
      induced by low-dose (0.1 microg/ml) but not high-dose (1 microg/ml) leptin. High
      dose leptin decreased Id mRNA and increased Ngn1 mRNA in neurosphere cells. The
      neuropeptide Y mRNA level in the cortical plate was lower in ob/ob than the wild
      type at E16 and E18. These results suggest that leptin maintains neural
      progenitors and is related to glial and neuronal development in embryos.

PMID- 16282356
TI  - Polychlorinated biphenyls exert selective effects on cellular composition of
      white matter in a manner inconsistent with thyroid hormone insufficiency.
AB  - Developmental exposure to polychlorinated biphenyls (PCBs) is associated with a
      variety of cognitive deficits in humans, and recent evidence implicates white
      matter development as a potential target of PCBs. Because PCBs are suspected of
      interfering with thyroid hormone (TH) signaling in the developing brain, and
      because TH is important in oligodendrocyte development, we tested the hypothesis
      that PCB exposure affects the development of white matter tracts by disrupting TH
      signaling. Pregnant Sprague Dawley rats were exposed to the PCB mixture Aroclor
      1254 (5 mg/kg), with or without cotreatment of goitrogens from gestational d 7
      until postnatal d 15. Treatment effects on white matter development were
      determined by separately measuring the cellular density and proportion of myelin
      associated glycoprotein (MAG)-positive, O4-positive, and glial fibrillary acidic
      protein (GFAP)-positive cells in the genu of the corpus callosum (CC) and in the
      anterior commissure (AC). Hypothyroidism decreased the total cell density of the
      CC and AC as measured by 4',6-diamidino-2-phenylindole dihydrochloride (DAPI)
      staining and produced a disproportionate decrease in MAG-positive oligodendrocyte
      density with a simultaneous increase in GFAP-positive astrocyte density. These
      data indicate that hypothyroidism reduces cellular density of CC and AC and
      fosters astrocyte development at the expense of oligodendrocyte density. In
      contrast, PCB exposure significantly reduced total cell density but did not
      disproportionately alter MAG-positive oligodendrocyte density or change the ratio
      of MAG-positive oligodendrocytes to GFAP-positive astrocytes. Thus, PCB exposure
      mimicked some, but not all, of the effects of hypothyroidism on white matter
      composition.

PMID- 16282357
TI  - Analysis of unilateral adrenal hyperplasia with primary aldosteronism from the
      aspect of messenger ribonucleic acid expression for steroidogenic enzymes: a
      comparative study with adrenal cortices adhering to aldosterone-producing
      adenoma.
AB  - Unilateral adrenal hyperplasia with primary aldosteronism is very rare and shows
      similar endocrine features to aldosterone-producing adenoma and bilateral adrenal
      hyperplasia. In this study, the mRNA expression of steroidogenic enzymes in
      unilateral adrenal hyperplasia was examined by in situ hybridization. We found
      subcapsular micronodules composed of spironolactone body-containing cells, which
      showed intense expression for 3beta-hydroxysteroid dehydrogenase, 11beta
      hydroxylase, 18-hydroxylase, and 21-hydroxylase but not 17alpha-hydroxylase,
      indicating aldosterone production. This expression pattern was the same as that
      in unilateral multiple adrenocortical micronodules, reported recently.
      Additionally, it was noted that a nodule with active aldosterone production was
      closely adjacent to one showing intense 17alpha-hydroxylase expression. In the
      adrenal cortices adhering to aldosterone-producing adenoma, the majority of
      hyperplastic zona glomerulosa and hyperplastic nodules demonstrated a decreased
      steroidogenic activity. However, minute nodules indicative of active aldosterone
      production were found at high frequency. These results suggest that the
      subcapsular micronodules observed might be the root of aldosterone-producing
      adenoma. Furthermore, we emphasize the need for long-term follow-up after
      unilateral adrenalectomy or enucleation of the adenoma because of the possibility
      that buds with autonomous aldosterone production may still be present in the
      contralateral or remaining adrenal tissue.

PMID- 16282358
TI  - A novel role for endogenous pituitary adenylate cyclase activating polypeptide in
      the magnocellular neuroendocrine system.
AB  - Central release of vasopressin (VP) by the magnocellular neuroendocrine cells
      (MNCs) responsible for systemic VP release is believed to be important in
      modulating the activity of these neurons during dehydration. Central VP release
      from MNC somata and dendrites is stimulated by both dehydration and pituitary
      adenylate cyclase activating polypeptide (PACAP). Although PACAP is expressed in
      MNCs, its potential role in the magnocellular response to dehydration is
      unexplored. The current study demonstrates that prolonged dehydration increases
      immunoreactivity for PACAP-27, PACAP-38, and the type I PACAP receptor in the
      supraoptic nucleus (SON) of the rat. In addition, PACAP stimulates local VP
      release in the euhydrated rat SON in vitro, and this effect is reduced by the
      PACAP receptor antagonist PAC(6-27) (100 nm), suggesting the participation of
      PACAP receptors. Concomitant with its effects on local VP release, PACAP also
      reduces basal glutamate and aspartate release in the euhydrated rat SON.
      Furthermore, somatodendritic VP release elicited by acute dehydration is blocked
      by PAC(6-27), suggesting that endogenous PACAP participates in this response.
      Consistent with this, RIA revealed that local PACAP-38 release within the SON is
      significantly elevated during acute dehydration. These results suggest that
      prolonged activation of hypothalamic MNCs is accompanied by up-regulation of
      PACAP and the type I PACAP receptor in these cells and that somatodendritic VP
      release in response to acute dehydration is mediated by activation of PACAP
      receptors by endogenous PACAP released within the SON. A potential role for PACAP
      in promoting efficient, but not exhaustive, systemic release of VP from MNCs
      during physiological challenge is discussed.

PMID- 16282359
TI  - Suppression of adiponectin gene expression by histone deacetylase inhibitor
      valproic acid.
AB  - Valproic acid (VPA) has been used for the treatment of epilepsy and bipolar
      disorders for more than 30 yr. Obesity and insulin resistance are common side
      effects of VPA treatment. Adiponectin is an adipocyte-derived protein that plays
      an important role in controlling insulin sensitivity and glucose homeostasis. In
      this report, we examined the effects of VPA on adiponectin gene expression in
      C57BL/6J mice and in differentiated 3T3-L1 adipocytes. VPA treatment
      significantly decreased adiponectin protein and mRNA levels in both mice and 3T3
      L1 adipocytes. The adipocyte study showed that VPA inhibited adiponectin gene
      expression in a dose- and time-dependent manner. Repression of adiponectin
      expression by VPA occurred at the transcription level and correlated with
      inhibition of histone deacetylase activity. Therapeutic concentrations of VPA
      increased overall histone acetylation and increased adiponectin promoter-driven
      luciferase expression in fibroblasts, but decreased adiponectin promoter activity
      in differentiated 3T3-L1 adipocytes. VPA treatment decreased adipogenic
      transcription factor CCAAT/enhancer binding protein-alpha (C/EBPalpha) levels and
      binding of C/EBPalpha to the adiponectin promoter without altering the levels of
      peroxisome proliferator-activated receptor-gamma and steroid regulatory element
      binding protein-1. Furthermore, VPA did not suppress adiponectin gene expression
      in C/EBPalpha gene-deficient adipocytes that stably expressed exogenous
      peroxisome proliferator-activated receptor-gamma2. Together, these results
      demonstrate that histone deacetylase inhibitor VPA suppresses adiponectin gene
      expression in mature adipocytes. The study also provides evidence that diminished
      C/EBPalpha protein level and decreased binding at the adiponectin promoter
      mediate the inhibitory effects of VPA on adiponectin gene transcription.

PMID- 16282360
TI  - TRPC1 functions as a store-operated Ca2+ channel in intestinal epithelial cells
      and regulates early mucosal restitution after wounding.
AB  - An increase in cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)) results from
      Ca(2+) release from intracellular stores and extracellular Ca(2+) influx through
      Ca(2+)-permeable ion channels and is crucial for initiating intestinal epithelial
      restitution to reseal superficial wounds after mucosal injury. Capacitative
      Ca(2+) entry (CCE) induced by Ca(2+) store depletion represents a major Ca(2+)
      influx mechanism, but the exact molecular components constituting this process
      remain elusive. This study determined whether canonical transient receptor
      potential (TRPC)1 served as a candidate protein for Ca(2+)-permeable channels
      mediating CCE in intestinal epithelial cells and played an important role in
      early epithelial restitution. Normal intestinal epithelial cells (the IEC-6 cell
      line) expressed TRPC1 and TPRC5 and displayed typical records of whole cell store
      operated Ca(2+) currents and CCE generated by Ca(2+) influx after depletion of
      intracellular stores. Induced TRPC1 expression by stable transfection with the
      TRPC1 gene increased CCE and enhanced cell migration during restitution.
      Differentiated IEC-Cdx2L1 cells induced by forced expression of the Cdx2 gene
      highly expressed endogenous TRPC1 and TRPC5 and exhibited increased CCE and cell
      migration. Inhibition of TRPC1 expression by small interfering RNA specially
      targeting TRPC1 not only reduced CCE but also inhibited cell migration after
      wounding. These findings strongly suggest that TRPC1 functions as store-operated
      Ca(2+) channels and plays a critical role in intestinal epithelial restitution by
      regulating CCE and intracellular [Ca(2+)](cyt).

PMID- 16282361
TI  - Substrate specificity of human ABCC4 (MRP4)-mediated cotransport of bile acids
      and reduced glutathione.
AB  - The multidrug resistance protein ABCC4 (MRP4), a member of the ATP-binding
      cassette superfamily, mediates ATP-dependent unidirectional efflux of organic
      anions out of cells. Previous studies showed that human ABCC4 is localized to the
      sinusoidal membrane of hepatocytes and mediates, among other substrates, the
      cotransport of reduced glutathione (GSH) with bile acids. In the present study,
      using inside-out membrane vesicles, we demonstrated that human ABCC4 in the
      presence of physiological concentrations of GSH has a high affinity for the
      taurine and glycine conjugates of the common natural bile acids as well as the
      unconjugated bile acid cholate. Chenodeoxycholyltaurine and
      chenodeoxycholylglycine were the GSH cosubstrates with the highest affinities for
      ABCC4, with K(m) values of 3.6 and 5.9 microM, respectively.
      Ursodeoxycholyltaurine and ursodeoxycholylglycine were cotransported together
      with GSH by ABCC4 with K(m) values of 7.8 and 12.5 microM, respectively, but no
      transport of ursodeoxycholate and deoxycholate was observed. The simultaneous
      transport of labeled GSH and cholyltaurine or cholylglycine was demonstrated in
      double-labeled cotransport experiments with a bile acid-to-GSH ratio of
      approximately 1:22. K(m) values of the bile acids for ABCC4 were in a range
      similar to those reported for the canalicular bile salt export pump ABCB11. Under
      physiological conditions, the sinusoidal ABCC4 may compete with canalicular
      ABCB11 for bile acids and thereby play a key role in determining the hepatocyte
      concentration of bile acids. In cholestatic conditions, ABCC4 may become a key
      pathway for efflux of bile acids from hepatocytes into blood.

PMID- 16282363
TI  - Secretion of MCP-1/CCL2 by bile duct epithelia induces myofibroblastic
      transdifferentiation of portal fibroblasts.
AB  - Portal fibroblasts (PF) are fibrogenic liver cells distinct from hepatic stellate
      cells (HSC). Recent evidence suggests that PF may be important mediators of
      biliary fibrosis and cirrhosis. The cytokine monocyte chemoattractant protein-1
      (MCP-1)/CCL2 is upregulated in biliary fibrosis by bile duct epithelia (BDE) and
      induces functional responses in HSC. Thus we hypothesized that release of MCP-1
      may mediate biliary fibrosis. We report that PF express functional receptors for
      MCP-1 that are distinct from the receptor CCR2. MCP-1 induces proliferation,
      increase and redistribution of alpha-smooth muscle (alpha-SMA) expression, loss
      of the ectonucleotidase NTPDase2, and upregulation of alpha(1)-procollagen
      production in PF. BDE secretions induce alpha-SMA levels in PF, and this is
      inhibited by MCP-1 blocking antibody. Together, these data suggest that BDE
      regulate PF proliferation and myofibroblastic transdifferentiation in a paracrine
      fashion via release of MCP-1.

PMID- 16282362
TI  - Functional and biochemical characterization of epithelial
      bactericidal/permeability-increasing protein.
AB  - Epithelial cells of many mucosal organs have adapted to coexist with microbes and
      microbial products. In general, most studies suggest that epithelial cells
      benefit from interactions with commensal microorganisms present at the lumenal
      surface. However, potentially injurious molecules found in this microenvironment
      also have the capacity to elicit local inflammatory responses and even systemic
      disease. We have recently demonstrated that epithelia cells express the anti
      infective molecule bactericidal/permeability-increasing protein (BPI). Here, we
      extend these findings to examine molecular mechanisms of intestinal epithelial
      cell (IEC) BPI expression and function. Initial experiments revealed a variance
      of BPI mRNA and protein expression among various IEC lines. Studies of BPI
      promoter expression in IECs identified regulatory regions of the BPI promoter and
      revealed a prominent role for CCAAT/enhancer binding protein and especially
      Sp1/Sp3 in the basal regulation of BPI. To assess the functional significance of
      this protein, we generated an IEC line stably transfected with full-length BPI.
      We demonstrated that, whereas epithelia express markedly less BPI protein than
      neutrophils, epithelial BPI contributes significantly to bacterial killing and
      attenuating bacterial-elicted proinflammatory signals. Additional studies in
      murine tissue ex vivo revealed that BPI is diffusely expressed along the crypt
      villous axis and that epithelial BPI levels decrease along the length of the
      intestine. Taken together, these data confirm the transcriptional regulation of
      BPI in intestinal epithelia and provide insight into the relevance of BPI as an
      anti-infective molecule at intestinal surfaces.

PMID- 16282364
TI  - Physiology of the esophageal pressure transition zone: separate contraction waves
      above and below.
AB  - Manometrically measured peristaltic pressure amplitude displays a well-defined
      trough in the upper esophagus. Whereas this manometric "transition zone" (TZ) has
      been associated with striated-to-smooth muscle fiber transition, the underlying
      physiology of the TZ and its role in bolus transport are unclear. A computer
      model study of bolus retention in the TZ showed discoordinated distinct
      contraction waves above and below. Our aim was to test the hypothesis that
      distinct upper/lower contraction waves above/below the manometric TZ are normal
      physiology and to quantify space-time coordination between tone and bolus
      transport through the TZ. Eighteen normal barium swallows were analyzed in 6
      subjects with concurrent 21-channel high-resolution manometry and digital
      fluoroscopy. From manometry, the TZ center (nadir pressure amplitude) and the
      upper/lower margins of the pressure trough were objectively quantified. Using
      fluoroscopy, we quantified space-time trajectories of the bolus tail and bolus
      tail pressures and maximum intraluminal pressures proximal to the tail with their
      space-time trajectories. In every swallow, the bolus tail followed distinct
      trajectories above/below the TZ, separated by a well-defined spatial "jump" that
      terminated an upper contraction wave and initiated a lower contraction wave (3.32
      +/- 1.63 cm, P = 0.0004). An "indentation wave" always formed within the TZ
      distal to the upper wave, increasing in amplitude until the lower wave was
      initiated. As the upper contraction wave tail entered the TZ, it slowed and the
      tail pressure reduced rapidly, while indentation wave pressure increased to
      normal tail pressure values at the initiation of the lower wave. The TZ was a
      special zone of segmental contraction. The TZ is, physiologically, the transition
      from an upper contraction wave originating in the proximal striated esophagus to
      a lower contraction wave that moves into the distal smooth muscle esophagus.
      Complete bolus transport requires coordination of upper/lower waves and
      sufficient segmental squeeze to fully clear the bolus from the TZ during the
      transition period.

PMID- 16282365
TI  - Maternal dietary fat alters amniotic fluid and fetal intestinal membrane
      essential n-6 and n-3 fatty acids in the rat.
AB  - We investigated whether maternal fat intake alters amniotic fluid and fetal
      intestine phospholipid n-6 and n-3 fatty acids. Female rats were fed a 20% by
      weight diet from fat with 20% linoleic acid (LA; 18:2n-6) and 8% alpha-linolenic
      acid (ALA; 18:3n-3) (control diet, n = 8) or 72% LA and 0.2% ALA (n-3 deficient
      diet, n = 7) from 2 wk before and then throughout gestation. Amniotic fluid and
      fetal intestine phospholipid fatty acids were analyzed at day 19 gestation using
      HPLC and gas-liquid chromotography. Amniotic fluid had significantly lower
      docosahexaenoic acid (DHA; 22:6n-3) and higher docosapentaenoic acid (DPA; 22:5n
      6) levels in the n-3-deficient group than in the control group (DHA: 1.29 +/-
      0.10 and 6.29 +/- 0.33 g/100 g fatty acid; DPA: 4.01 +/- 0.35 and 0.73 +/- 0.15
      g/100 g fatty acid, respectively); these differences in DHA and DPA were present
      in amniotic fluid cholesterol esters and phosphatidylcholine (PC). Fetal
      intestines in the n-3-deficient group had significantly higher LA, arachidonic
      acid (20:4n-6), and DPA levels; lower eicosapentaenoic acid (EPA; 20:5n-3) and
      DHA levels in PC; and significantly higher DPA and lower EPA and DHA levels in
      phosphatidylethanolamine (PE) than in the control group; the n-6-to-n-3 fatty
      acid ratio was 4.9 +/- 0.2 and 32.2 +/- 2.1 in PC and 2.4 +/- 0.03 and 17.1 +/-
      0.21 in PE in n-3-deficient and control group intestines, respectively. We
      demonstrate that maternal dietary fat influences amniotic fluid and fetal
      intestinal membrane structural lipid essential fatty acids. Maternal dietary fat
      can influence tissue composition by manipulation of amniotic fluid that is
      swallowed by the fetus or by transport across the placenta.

PMID- 16282366
TI  - The mammalian exercise pressor reflex in health and disease.
AB  - The exercise pressor reflex (a peripheral neural reflex originating in skeletal
      muscle) contributes significantly to the regulation of the cardiovascular system
      during exercise. Exercise-induced signals that comprise the afferent arm of the
      reflex are generated by activation of mechanically (muscle mechanoreflex) and
      chemically sensitive (muscle metaboreflex) skeletal muscle receptors. Activation
      of these receptors and their associated afferent fibres reflexively adjusts
      sympathetic and parasympathetic nerve activity during exercise. In heart failure,
      the cardiovascular response to exercise is augmented. Owing to the peripheral
      skeletal myopathy that develops in heart failure (e.g. muscle atrophy, decreased
      peripheral blood flow, fibre-type transformation and reduced oxidative capacity),
      the exercise pressor reflex has been implicated as a possible mechanism by which
      the cardiovascular response to physical activity is exaggerated in this disease.
      Accumulating evidence supports this conclusion. This review therefore focuses on
      the role of the exercise pressor reflex in regulating the cardiovascular system
      during exercise in both health and disease. Updates on our current understanding
      of the exercise pressor reflex neural pathway as well as experimental models used
      to study this reflex are presented. In addition, special emphasis is placed on
      the changes in exercise pressor reflex activity that develop in heart failure,
      including the contributions of the muscle mechanoreflex and metaboreflex to this
      pressor reflex dysfunction.

PMID- 16282367
TI  - Mathematical models of periodic breathing and their usefulness in understanding
      cardiovascular and respiratory disorders.
AB  - Periodic breathing is an unusual form of breathing with oscillations in minute
      ventilations and with repetitive apnoeas or near apnoeas. Reported initially in
      patients with heart failure or stroke, it was later recognized to occur
      especially during sleep. The recurrent hypoxia and surges of sympathetic activity
      that often occur during the apnoeas have serious health consequences.
      Mathematical models have helped greatly in the understanding of the causes of
      recurrent apnoeas. It is unlikely that every instance of periodic breathing has
      the same cause, but many result from instability in the feedback control involved
      in the chemical regulation of breathing caused by increased controller and plant
      gains and delays in information transfer. Even when it is not the main cause of
      the periodic breathing, unstable control modifies the ventilatory pattern and
      sometimes intensifies the recurrent apnoeas. The characteristics of disturbances
      to breathing and their interaction with the control system can be critical in
      determining ventilation responses and the occurrence of periodic breathing. Large
      abrupt changes in ventilation produced, for example, in the transition from
      waking to sleep and vice versa, or in the transition from breathing to apnoea,
      are potent factors causing periodic breathing. Mathematical models show that
      periodic breathing is a 'systems disorder' produced by the interplay of multiple
      factors. Multiple factors contribute to the occurrence of periodic breathing in
      congestive heart failure and cerebrovascular disease, increasing treatment
      options.

PMID- 16282368
TI  - Effects of oestrogen treatment and angiotensin-converting enzyme inhibition on
      the microvasculature of ovariectomized spontaneously hypertensive rats.
AB  - We investigated the role of oestrogen in the function and structure of the
      microcirculation of female spontaneously hypertensive rats (SHRs), and evaluated
      the effect of 17beta-oestradiol on their cardiovascular response to
      pharmacological agents that block the formation of angiotensin II. Ten-week-old
      SHRs were randomly assigned to the following groups: intact, ovariectomized, and
      ovariectomized treated with 17beta-oestradiol (1.5 mg delivered over 60 days)
      and/or captopril (5 mg kg(-1) day(-1) for 8 weeks). Systolic blood pressure was
      determined from the time of ovariectomy up to 18 weeks of age, at which time
      endothelial function and microvascular density in skeletal muscle were evaluated.
      Both 17beta-oestradiol and captopril prevented development of hypertension in
      ovariectomized rats. Furthermore, coadministration of both drugs had a greater
      antihypertensive effect than either one alone. Acetylcholine-induced
      vasodilatation was impaired in ovariectomized SHRs, and the response was improved
      by treatment with 17beta-oestradiol and/or captopril. In addition, 17beta
      oestradiol replacement in ovariectomized rats enhanced the effect of captopril on
      acetylcholine-induced vasodilatation. Ovariectomized rats also showed lower
      microvascular density than intact rats, an effect that was prevented by 17beta
      oestradiol replacement or captopril treatment and, to a significantly larger
      extent, by coadministration of both. We concluded that both 17beta-oestradiol and
      captopril attenuated the development of hypertension and improved the impairment
      in microvascular density of ovariectomized SHRs. Moreover, when simultaneously
      administered, oestradiol and captopril had an additive effect on blood pressure
      and the microvasculature.

PMID- 16282369
TI  - Clonidine-evoked respiratory effects in anaesthetized rats.
AB  - The respiratory effects of stimulation of alpha2-adrenergic receptors were
      studied in spontaneously breathing anaesthetized rats that were neurally intact,
      or bilaterally vagotomized, or subjected to bilateral combined midcervical
      vagotomy and section of the carotid sinus nerves. An intravenous clonidine bolus
      (15 microg kg(-1)) evoked a prolonged slowing of the respiratory rate in all the
      neural states explored. Vagotomy reduced the early clonidine-evoked decline, but
      not the augmentation of tidal volume that followed the decline. After section of
      the carotid sinus nerves, clonidine challenge continued to decrease the
      respiratory rate, but not the tidal volume. Blockade of alpha2-adrenergic
      receptors with intravenous doses of SKF 86466 (200 microg kg(-1)) abolished all
      respiratory effects of the clonidine challenge. In all the neural states studied,
      clonidine evoked a significant short-lived rise in mean arterial blood pressure
      followed by a decrease below the respective prechallenge value. The SKF 86466
      pretreatment lowered mean arterial blood pressure control values and reduced the
      magnitude of postclonidine changes. These results indicate that: (i) clonidine
      evoked activation of alpha2-adrenergic receptors affects the two components of
      the breathing pattern differently, and this occurs beyond the lung vagi; and (ii)
      changes in tidal volume result from excitation of the carotid bodies and are
      coupled with centrally mediated slowing of the respiratory rhythm.

PMID- 16282370
TI  - Stress kinase signaling regulates androgen receptor phosphorylation,
      transcription, and localization.
AB  - Activation of signal transduction kinase cascades is known to alter androgen
      receptor (AR) activity, but the molecular mechanisms are still poorly defined.
      Here we show that stress kinase signaling regulates Ser 650 phosphorylation and
      AR nuclear export. In LNCaP prostate cancer cells, activation of either MAPK
      kinase (MKK) 4:c-Jun N-terminal kinase (JNK) or MKK6:p38 signaling pathways
      increased Ser 650 phosphorylation, whereas pharmacologic inhibition of JNK or p38
      signaling led to a reduction of AR Ser 650 phosphorylation. Both p38alpha and
      JNK1 phosphorylated Ser 650 in vitro. Small interfering RNA-mediated knockdown of
      either MKK4 or MKK6 increased endogenous prostate-specific antigen (PSA)
      transcript levels, and this increase was blocked by either bicalutamide or AR
      small interfering RNA. Stress kinase inhibition of PSA transcription is,
      therefore, dependent on the AR. Similar experiments involving either activation
      or inhibition of MAPK/ERK kinase:ERK signaling had little effect on Ser 650
      phosphorylation or PSA mRNA levels. Ser 650 is proximal to the DNA binding domain
      that contains a nuclear export signal. Mutation of Ser 650 to alanine reduced
      nuclear export of the AR, whereas mutation of Ser 650 to the phosphomimetic amino
      acid aspartate restored AR nuclear export. Pharmacologic inhibition of stress
      kinase signaling reduced wild-type AR nuclear export equivalent to the S650A
      mutant without affecting nuclear export of the S650D mutant. Our data suggest
      that stress kinase signaling and nuclear export regulate AR transcriptional
      activity.

PMID- 16282371
TI  - Functional analysis of Hes-1 in preadipocytes.
AB  - Notch signaling blocks differentiation of 3T3-L1 preadipocytes, and this can be
      mimicked by constitutive expression of the Notch target gene Hes-1. Although
      considered initially to function only as a repressor, recent evidence indicates
      that Hes-1 can also activate transcription. We show here that the domains of Hes
      1 needed to block adipogenesis coincide with those necessary for transcriptional
      repression. HRT1, another basic-helix-loop-helix protein and potential Hes-1
      partner, was also induced by Notch in 3T3-L1 cells but did not block
      adipogenesis, suggesting that Hes-1 functions primarily as a homodimer or
      possibly as a heterodimer with an unknown partner. Purification of Hes-1
      identified the Groucho/transducin-like enhancer of split family of corepressors
      as the only significant Hes-1 interacting proteins in vivo. An evaluation of
      global gene expression in preadipocytes identified approximately 200 Hes-1
      responsive genes comprising roughly equal numbers of up-regulated and down
      regulated genes. However, promoter analyses indicated that the down-regulated
      genes were significantly more likely to contain Hes-1 binding sites, indicating
      that Hes-1 is more likely to repress transcription of its direct targets. We
      conclude that Notch most likely blocks adipogenesis through the induction of Hes
      1 homodimers, which repress transcription of key target genes.

PMID- 16282372
TI  - Expression of bestrophin-1, the product of the VMD2 gene, modulates voltage
      dependent Ca2+ channels in retinal pigment epithelial cells.
AB  - Mutations in the VMD2 gene cause Best's disease, an inherited form of macular
      degeneration. The reduction in the light-peak amplitude in the patient's electro
      oculogram suggests that bestrophin-1 influences the membrane conductance of the
      retinal pigment epithelium (RPE). Systemic application of the L-type Ca2+ channel
      blocker nimodipine reduced the light-peak amplitude in the rat electroretinogram
      but not a- and b-waves. Expression of bestrophin-1 in a RPE cell line (RPE-J) led
      to changes in L-type channel properties. Wild-type bestrophin-1 induced an
      acceleration of activation kinetics of Ba2+ currents through L-type Ca2+ channels
      and a shift of the voltage-dependent activation to more negative values, closer
      to the resting potential of RPE cells. Expression of bestrophin-1 with Best
      disease-causing mutations led to comparable shifts in voltage-dependent
      activation but different effects on activation and inactivation kinetics.
      Bestrophin W93C exhibited slowed activation and inactivation, and bestrophin
      R218C accelerated the activation and inactivation. Thus, transfection of RPE
      cells with bestrophin-1 distinctively changed L-type Ca2+ channel kinetics and
      voltage-dependence. On the basis of these data, we propose that presence of
      bestrophin-1 influences kinetics and voltage-dependence of voltage-dependent Ca2+
      channels and that these effects might open new ways to understand the mechanisms
      leading to retinal degeneration in Best's disease.

PMID- 16282373
TI  - Phylogenetic engineering at an interface between large and small subunits imparts
      land-plant kinetic properties to algal Rubisco.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the rate
      limiting step of photosynthetic CO(2) fixation and, thus, limits agricultural
      productivity. However, Rubisco enzymes from different species have different
      catalytic constants. If the structural basis for such differences were known, a
      rationale could be developed for genetically engineering an improved enzyme.
      Residues at the bottom of the large-subunit alpha/beta-barrel active site of
      Rubisco from the green alga Chlamydomonas reinhardtii (methyl-Cys-256, Lys-258,
      and Ile-265) were previously changed through directed mutagenesis and chloroplast
      transformation to residues characteristic of land-plant Rubisco (Phe-256, Arg
      258, and Val-265). The resultant enzyme has decreases in carboxylation efficiency
      and CO(2)/O(2) specificity, despite the fact that land-plant Rubisco has greater
      specificity than the Chlamydomonas enzyme. Because the residues are close to a
      variable loop between beta-strands A and B of the small subunit that can also
      affect catalysis, additional substitutions were created at this interface. When
      large-subunit Val-221 and Val-235 were changed to land-plant Cys-221 and Ile-235,
      they complemented the original substitutions and returned CO(2)/O(2) specificity
      to the normal level. Further substitution with the shorter betaA-betaB loop of
      the spinach small subunit caused a 12-17% increase in specificity. The enhanced
      CO(2)/O(2) specificity of the mutant enzyme is lower than that of the spinach
      enzyme, but the carboxylation and oxygenation kinetic constants are nearly
      indistinguishable from those of spinach and substantially different from those of
      Chlamydomonas Rubisco. Thus, this interface between large and small subunits, far
      from the active site, contributes significantly to the differences in catalytic
      properties between algal and land-plant Rubisco enzymes.

PMID- 16282374
TI  - Visibility, visual awareness, and visual masking of simple unattended targets are
      confined to areas in the occipital cortex beyond human V1/V2.
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, we localize the neuronal correlates of visual awareness in the human brain
      by using visual masking illusions. We compare monoptic visual masking activation,
      which we find within all retinotopic visual areas, with dichoptic masking
      activation, which we find only in those retinotopic areas downstream of V2.
      Because monoptic and dichoptic masking are equivalent in magnitude perceptually,
      the present results establish a lower bound for maintenance of visual awareness
      of simple unattended targets. Moreover, we find that awareness-correlated
      circuits for simple targets are restricted to the occipital lobe. This finding
      provides evidence of an upper boundary in the visual hierarchy for visual
      awareness of simple unattended targets, thus constraining the location of
      circuits that maintain the visibility of simple targets to occipital areas beyond
      V1/V2.

PMID- 16282375
TI  - Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly.
AB  - Holoprosencephaly (HPE), a human developmental brain defect, usually is also
      associated with varying degrees of midline facial dysmorphism. Heterozygous
      mutations in the Sonic hedgehog (SHH) gene are the most common genetic lesions
      associated with HPE, and loss of Shh function in the mouse produces cyclopia and
      alobar forebrain development. The N-terminal domain (ShhNp) of Sonic hedgehog
      protein, generated by cholesterol-dependent autoprocessing and modification at
      the C terminus and by palmitate addition at the N terminus, is the active ligand
      in the Shh signal transduction pathway. Here, we analyze seven reported missense
      mutations (G31R, D88V, Q100H, N115K, W117G, W117R, and E188Q) that alter the N
      terminal signaling domain of Shh protein, and show that two of these mutations
      (Q100H and E188Q), which are questionably linked to HPE, produce no detectable
      effects on function. The remaining five alterations affect normal processing, Ptc
      binding, and signaling to varying degrees. These effects include introduction of
      a recognition site for furin-like proteases by the G31R alteration, resulting in
      cleavage of 11 amino acid residues from the N terminus of ShhNp and consequent
      reduced signaling potency. Two other alterations, W117G and W117R, cause
      temperature-dependent misfolding and retention in the sterol-poor endoplasmic
      reticulum, thus disrupting cholesterol-dependent autoprocessing.

PMID- 16282376
TI  - Nitric oxide-donating aspirin induces apoptosis in human colon cancer cells
      through induction of oxidative stress.
AB  - Nitric oxide-donating aspirin (NO-ASA) is a promising chemoprevention agent
      against colon cancer and other cancers. It consists of traditional ASA to which a
      NO-releasing moiety is bound through a spacer. NO-ASA inhibits colon cancer cell
      growth several hundred times more potently than does ASA. In Min mice, NO-ASA
      inhibited intestinal carcinogenesis without affecting cell proliferation. Thus,
      we examined whether NO-ASA's most important cell kinetic effect is the induction
      of apoptosis. After confirming induction of apoptosis in Min mice, we studied the
      underlying mechanism in human colon adenocarcinoma cells. NO-ASA's spacer formed
      a conjugate with glutathione, depleting glutathione stores. This induced
      oxidative stress (increased intracellular levels of peroxides and O(2)(.-)) leads
      to apoptosis by activating the intrinsic apoptosis pathway. NO-ASA disrupted
      adherens junctions by inducing cleavage of beta- and gamma-catenin, resulting in
      cell detachment. NO-ASA inhibited Wnt signaling by a dual mechanism: at low
      concentrations it blocked the formation of beta-catenin/Tcf complexes (dominant
      mechanism), and at higher concentrations it also cleaved beta-catenin. These
      findings provide a mechanism of action by a potent chemopreventive agent,
      underscore the significance of these pathways in regulating cell death in the
      context of cancer chemoprevention, and present a paradigm for developing agents
      with enhanced cancer cell growth inhibitory properties.

PMID- 16282377
TI  - Evaluation of current strategies and future priorities for improving health in
      developing countries.

PMID- 16282378
TI  - Cost effectiveness analysis of strategies for child health in developing
      countries.
AB  - OBJECTIVE: To determine the costs and effectiveness of selected child health
      interventions-namely, case management of pneumonia, oral rehydration therapy,
      supplementation or fortification of staple foods with vitamin A or zinc,
      provision of supplementary food with counselling on nutrition, and immunisation
      against measles. DESIGN: Cost effectiveness analysis. DATA SOURCES: Efficacy data
      came from published systematic reviews and before and after evaluations of
      programmes. For resource inputs, quantities came from literature and expert
      opinion, and prices from the World Health Organization Choosing Interventions
      that are Cost Effective (WHO-CHOICE) database, RESULTS: Cost effectiveness ratios
      clustered in three groups, with fortification with zinc or vitamin A as the most
      cost effective intervention, and provision of supplementary food and counselling
      on nutrition as the least cost effective. Between these were oral rehydration
      therapy, case management of pneumonia, vitamin A or zinc supplementation, and
      measles immunisation. CONCLUSIONS: On the grounds of cost effectiveness,
      micronutrients and measles immunisation should be provided routinely to all
      children, in addition to oral rehydration therapy and case management of
      pneumonia for those who are sick. The challenge of malnutrition is not well
      addressed by existing interventions.

PMID- 16282379
TI  - Cost effectiveness analysis of strategies for tuberculosis control in developing
      countries.
AB  - OBJECTIVE: To assess the costs and health effects of tuberculosis control
      interventions in Africa and South East Asia in the context of the millennium
      development goals. DESIGN: Cost effectiveness analysis based on an
      epidemiological model. SETTING: Analyses undertaken for two regions classified by
      WHO according to their epidemiological grouping-Afr-E, countries in sub-Saharan
      Africa with very high adult and high child mortality, and Sear-D, countries in
      South East Asia with high adult and high child mortality. DATA SOURCES: Published
      studies, costing databases, expert opinion. MAIN OUTCOME MEASURES: Costs per
      disability adjusted life year (DALY) averted in 2000 international dollars
      (dollarsInt). RESULTS: Treatment of new cases of smear-positive tuberculosis in
      DOTS programmes cost dollarsInt6-8 per DALY averted in Afr-E and dollarsInt7 per
      DALY averted in Sear-D at coverage levels of 50-95%. In Afr-E, adding treatment
      of smear-negative and extra-pulmonary cases at a coverage level of 95% cost
      dollarsInt95 per DALY averted; the addition of DOTS-Plus treatment for multidrug
      resistant cases cost dollarsInt123. In Sear-D, these costs were dollarsInt52 and
      dollarsInt226, respectively. The full combination of interventions could reduce
      prevalence and mortality by over 50% in Sear-D between 1990 and 2010, and by
      almost 50% between 2000 and 2010 in Afr-E. CONCLUSIONS: DOTS treatment of new
      smear-positive cases is the first priority in tuberculosis control, including in
      countries with high HIV prevalence. DOTS treatment of smear-negative and extra
      pulmonary cases and DOTS-Plus treatment of multidrug resistant cases are also
      highly cost effective. To achieve the millennium development goal for
      tuberculosis control, substantial extra investment is needed to increase case
      finding and implement interventions on a wider scale.

PMID- 16282380
TI  - Cost effectiveness analysis of strategies to combat HIV/AIDS in developing
      countries.
AB  - OBJECTIVE: To assess the costs and health effects of a range of interventions for
      preventing the spread of HIV and for treating people with HIV/AIDS in the context
      of the millennium development goal for combating HIV/AIDS. DESIGN: Cost
      effectiveness analysis based on an epidemiological model. SETTING: Analyses
      undertaken for two regions classified using the WHO epidemiological grouping-Afr
      E, countries in sub-Saharan Africa with very high adult and high child mortality,
      and Sear-D, countries in South East Asia with high adult and high child
      mortality. DATA SOURCES: Biological and behavioural parameters from clinical and
      observational studies and population based surveys. Intervention effects and
      resource inputs based on published reports, expert opinion, and the WHO-CHOICE
      database. MAIN OUTCOME MEASURES: Costs per disability adjusted life year (DALY)
      averted in 2000 international dollars (Int dollars). RESULTS: In both regions
      interventions focused on mass media, education and treatment of sexually
      transmitted infections for female sex workers, and treatment of sexually
      transmitted infections in the general population cost < Int150 dollars per DALY
      averted. Voluntary counselling and testing costs < Int350 dollars per DALY
      averted in both regions, while prevention of mother to child transmission costs <
      Int50 dollars per DALY averted in Afr-E but around Int850 dollars per DALY in
      Sear-D. School based education strategies and various antiretroviral treatment
      strategies cost between Int500 dollars and Int5000 dollars per DALY averted.
      CONCLUSIONS: Reducing HIV transmission could be done most efficiently through
      mass media campaigns, interventions for sex workers and treatment of sexually
      transmitted infections where resources are most scarce. However, prevention of
      mother to child transmission, voluntary counselling and testing, and school based
      education would yield further health gains at higher budget levels and would be
      regarded as cost effective or highly cost effective based on standard
      international benchmarks. Antiretroviral therapy is at least as cost effective in
      improving population health as some of these interventions.

PMID- 16282382
TI  - Are cost effective interventions enough to achieve the millennium development
      goals?

PMID- 16282381
TI  - Cost effectiveness analysis of strategies to combat malaria in developing
      countries.
AB  - OBJECTIVE: To determine the cost effectiveness of selected malaria control
      interventions in the context of reaching the millennium development goals for
      malaria. DESIGN: Generalised cost effectiveness analysis. DATA SOURCES: Efficacy
      data came from the literature and authors' calculations supported by expert
      opinion. Quantities for resource inputs came from the literature and from expert
      opinion; prices came from the WHO-CHOICE database. METHODS: Costs were assessed
      in year 2000 international dollars, and effects were assessed as disability
      adjusted life years averted by a 10 year implementation programme. Analysis was
      restricted to sub-Saharan regions where the most deadly form of malaria,
      Plasmodium falciparum, is most prevalent. The impact on population health for
      various interventions, and their combinations, was evaluated at selected coverage
      levels by using a state-transition model. Sensitivity analysis was done for age
      weights and discounting. RESULTS: High coverage with artemisinin based
      combination treatments was found to be the most cost effective strategy for
      control of malaria in most countries in sub-Saharan Africa. CONCLUSIONS: A much
      larger infusion of resources than those currently available is needed to make
      headway in the fight to roll back malaria. On cost effectiveness grounds, in most
      areas in sub-Saharan Africa greater coverage with highly effective combination
      treatments should be the cornerstone of malaria control. However, treatment alone
      can achieve less than half the total benefit obtainable through a combination of
      interventions-scaling up the use of impregnated mosquito nets or indoor spraying
      with insecticides is also critical. Intermittent presumptive treatment of
      pregnant women can bring a small but important additional health gain at
      relatively low cost.

PMID- 16282383
TI  - Trauma care research and the war on uncertainty.

PMID- 16282384
TI  - Persistent high stroke mortality in Bangladeshi populations.

PMID- 16282386
TI  - Political lead essential to avoid panic when flu strikes.

PMID- 16282385
TI  - Diabetes and the quality and outcomes framework.

PMID- 16282387
TI  - International conference "mildly optimistic" about bird flu.

PMID- 16282388
TI  - UK patient safety is improving.

PMID- 16282389
TI  - US has most reports of medical errors.

PMID- 16282390
TI  - Merck cleared in personal injury case against Vioxx.

PMID- 16282392
TI  - First NHS funded live liver transplant programme to go ahead.

PMID- 16282393
TI  - US panel recommends young children receive hepatitis A vaccination.

PMID- 16282396
TI  - FDA investigates direct to consumer adverts.

PMID- 16282400
TI  - Total workplace injuries up despite reduction within construction industry.

PMID- 16282397
TI  - Bush announces US plan for flu pandemic.

PMID- 16282401
TI  - British American Tobacco is drawn into Israeli damages claim.

PMID- 16282403
TI  - Researchers investigate potential use of plant as a pain killer.

PMID- 16282404
TI  - WHO official warns of crisis in supply of low cost AIDS drugs.

PMID- 16282406
TI  - The long road to the top.

PMID- 16282407
TI  - Cost effectiveness analysis of strategies for maternal and neonatal health in
      developing countries.
AB  - OBJECTIVE: To determine the costs and benefits of interventions for maternal and
      newborn health to assess the appropriateness of current strategies and guide
      future plans to attain the millennium development goals. DESIGN: Cost
      effectiveness analysis. SETTING: Two regions classified by the World Health
      Organization according to their epidemiological grouping: Afr-E, those countries
      in sub-Saharan Africa with very high adult and high child mortality, and Sear-D,
      comprising countries in South East Asia with high adult and high child mortality.
      DATA SOURCES: Effectiveness data from several sources, including trials,
      observational studies, and expert opinion. For resource inputs, quantities came
      from WHO guidelines, literature, and expert opinion, and prices from the WHO
      choosing interventions that are cost effective database. MAIN OUTCOME MEASURES:
      Cost per disability adjusted life year (DALY) averted in year 2000 international
      dollars. RESULTS: The most cost effective mix of interventions was similar in Afr
      E and Sear-D. These were the community based newborn care package, followed by
      antenatal care (tetanus toxoid, screening for pre-eclampsia, screening and
      treatment of asymptomatic bacteriuria and syphilis); skilled attendance at birth,
      offering first level maternal and neonatal care around childbirth; and emergency
      obstetric and neonatal care around and after birth. Screening and treatment of
      maternal syphilis, community based management of neonatal pneumonia, and steroids
      given during the antenatal period were relatively less cost effective in Sear-D.
      Scaling up all of the included interventions to 95% coverage would halve neonatal
      and maternal deaths. CONCLUSION: Preventive interventions at the community level
      for newborn babies and at the primary care level for mothers and newborn babies
      are extremely cost effective, but the millennium development goals for maternal
      and child health will not be achieved without universal access to clinical
      services as well.

PMID- 16282408
TI  - Shoulder pain: diagnosis and management in primary care.

PMID- 16282409
TI  - Keeping up: learning in the workplace.

PMID- 16282410
TI  - Time to reassess strategies for improving health in developing countries.

PMID- 16282411
TI  - Methods to assess the costs and health effects of interventions for improving
      health in developing countries.

PMID- 16282412
TI  - Use of private health care in the NHS.

PMID- 16282413
TI  - Improving surveillance of MRSA bacteraemia: the tragedy of targets.

PMID- 16282414
TI  - Improving surveillance of MRSA bacteraemia: Scottish data prompt query of
      significance of MRSA isolated from blood in acute admissions.

PMID- 16282415
TI  - Improving surveillance of MRSA bacteraemia: data from north west England support
      Oxfordshire findings.

PMID- 16282416
TI  - Orphan drugs and the NHS: fairness in health care entails more than cost
      effectiveness.

PMID- 16282417
TI  - Orphan drugs and the NHS: consider whom drug regulation is designed to protect.

PMID- 16282418
TI  - Detecting fabricated or induced illness in children: covert video surveillance
      can protect children and parents if rules are clear.

PMID- 16282419
TI  - Detecting fabricated or induced illness in children: are we ready for covert
      video surveillance?

PMID- 16282420
TI  - Obesity, like atherosclerosis, starts early in life.

PMID- 16282421
TI  - Misdiagnosis of conversion symptoms: conversion disorders still exist.

PMID- 16282422
TI  - Misdiagnosis of conversion symptoms: we may have gone full circle.

PMID- 16282423
TI  - Total smoking ban is accepted in New Zealand.

PMID- 16282424
TI  - Asymptomatic spread of flu is not proved.

PMID- 16282425
TI  - Adipose tissue extracts plasma ammonia after sprint exercise in women and men.
AB  - This study evaluates a possible contribution of adipose tissue to the elimination
      of plasma ammonia (NH(3)) after high-intensity sprint exercise. In 14 healthy men
      and women, repeated blood samples for plasma NH(3) analyses were obtained from
      brachial artery and from a subcutaneous abdominal vein before and after three
      repeated 30-s cycle sprints separated by 20 min of recovery. Biopsies from
      subcutaneous abdominal adipose tissue were obtained and analyzed for glutamine
      and glutamate content. After exercise, both arterial and abdominal venous plasma
      NH(3) concentrations were lower in women than in men (P < 0.01 and P < 0.001,
      respectively). All postexercise measurements showed sex-independent positive
      arterio-subcutaneous abdominal venous plasma NH(3) concentration differences (a
      v(abd)), indicating a net uptake of NH(3) from blood to adipose tissue. However,
      the fractional extraction (a-v(abd)/a) of NH(3) was higher in women than in men
      (P < 0.05). The glutamine-to-glutamate ratio in adipose tissue was increased
      after the second and third bout of sprint exercise (2.2 +/- 0.7 and 1.6 +/- 0.8,
      respectively) compared with the value at rest (1.2 +/- 0.6), suggesting a
      reaction of the extracted NH(3) with glutamate resulting in its conversion to
      glutamine. Adipose tissue may thus play an important physiological role in
      eliminating plasma NH(3) and thereby reducing the risk of NH(3) intoxication
      after high-intensity exercise.

PMID- 16282426
TI  - Frequency-domain characteristics and filtering of blood flow following the onset
      of exercise: implications for kinetics analysis.
AB  - We examined the validity and usefulness of a low-pass filter (LPFILTER) to reduce
      point-to-point variability and enhance parameter estimation of the kinetics of
      blood flow (BF). Computer simulations were used to determine the power spectrum
      of simulated responses. Moreover, we studied the leg BF response to a single
      transition in four subjects during supine knee-extension exercise using three
      methods of data processing [beat-by-beat, average of 3 cardiac cycles (AVG3
      BEATS), and LPFILTER]. The power spectrum of BF containing the kinetics
      information (<or=0.2 Hz) did not overlap with the oscillations due to muscle
      contraction and cardiac cycle (simulations and Doppler measurements). There were
      no significant differences between the parameter estimates for a two-exponential
      model using Beat-by-Beat, AVG3 BEATS, and LPFILTER (P>0.05; n=4). However,
      LPFILTER (cutoff=0.2 Hz) resulted in a significantly lower standard error of the
      estimate for all parameters (P<0.05). The means+/-SD for the standard error of
      the estimate for Beat-by-Beat, AVG3 BEATS, and LPFILTER were, respectively, time
      constant-phase 1=5.0+/-1.1 s, 4.5+/-2.1 s, and 0.3+/-0.2 s; time delay-phase
      2=17.8+/-7.9 s, 12.8+/-7.5 s, and 1.4+/-1.4 s; time constant-phase 2=15.8+/-4.6
      s, 9.9+/-2.9 s, and 1.1+/-0.5 s. In conclusion, LPFILTER appeared to be a valid
      procedure providing a high signal-to-noise ratio and data density and thus
      LPFILTER resulted in the smallest confidence interval for parameter estimates of
      BF kinetics.

PMID- 16282427
TI  - Hindlimb unloading increases muscle content of cytosolic but not nuclear Id2 and
      p53 proteins in young adult and aged rats.
AB  - This study tested the hypothesis that inhibitor of differentiation-2 (Id2), p53,
      and heat shock proteins (HSP) are responsive to suspension-induced muscle
      atrophy. Fourteen days of hindlimb suspension were used to unload the hindlimbs
      and induce atrophy in gastrocnemius muscles of young adult and aged rats.
      Following suspension, medial gastrocnemius muscle wet weight was reduced by
      approximately 30%, and the muscle wet weight normalized to the animal body weight
      decreased by 11 and 15% in young adult and aged animals, respectively. mRNA
      abundances of Id2, p53, HSP70-2, and HSP27 did not change with suspension,
      whereas HSP70-1 mRNA content was lower in the suspended muscle compared with the
      control muscle in both young adult and aged animals. Our immunoblot analyses
      indicated that protein expressions of HSP70 and HSP60 were not different between
      suspended and control muscles in both ages, whereas HSP27 protein content was
      increased in suspended muscle relative to control muscle only in young adult
      animals. Id2 and p53 protein contents were elevated in the cytosolic fraction of
      suspended muscle compared with the control muscle in both young and aged animals,
      but these changes were not found in the nuclear protein fraction. Furthermore,
      compared with young adult, aged muscles had a lower HSP70-1 mRNA content but
      higher HSP70-2 mRNA content and protein contents of Id2, p53, HSP70, and HSP27.
      These findings are consistent with the hypothesis that Id2 and p53 are responsive
      to unloading-induced muscle atrophy. Moreover, our data indicate that aging is
      accompanied with altered abundances of HSP70-1 and HSP70-2 mRNA, in addition to
      Id2, p53, HSP70, and HSP27 protein in rat gastrocnemius muscle.

PMID- 16282428
TI  - A test to establish maximum O2 uptake despite no plateau in the O2 uptake
      response to ramp incremental exercise.
AB  - The O2 uptake (Vo2) response to ramp incremental (RI) exercise does not
      consistently demonstrate plateau-like behavior at the limit of tolerance, and
      hence the requirements for a maximum Vo2 commonly are not met, despite apparent
      maximum effort. We sought to determine whether an appended step exercise (SE)
      test at a work rate greater than that achieved in a preceding ramp test would
      establish the plateau criterion. Seven healthy male adults performed RI cycle
      ergometry (20 W/min) to the limit of tolerance, followed by 5-min recovery (20 W)
      and then an SE test at 105% (RISE-105) of the final work rate (WRpeak) achieved
      during RI. Five of these subjects also performed an RI test followed by SE at 95%
      WRpeak (RISE-95). Vo2 was measured breath by breath using a turbine and mass
      spectrometer. The average of the final 15 s of RI or SE was used to establish
      respective Vo2 peaks. When Vo2 peak was approached, a constant Vo2 value (e.g., a
      plateau) was not discernable during any RI or SE component of the tests. Although
      the WRpeak [mean (SD)] was higher during the SE portion [359 W (SD 31)] than
      during the RI portion [341 W (SD 29)] of the RISE-105, the peak Vo2 was not
      different [SE, 4.30 l/min (SD 0.51); RI, 4.33 l/min (SD 0.52); P=0.49; n=7].
      Similarly, in the RISE-95 test, WRpeak was 310 W (SD 31) for the SE portion and
      326 W (SD 32) for the RI portion, yet the peak Vo2 values were not different [SE,
      4.12 l/min (SD 0.53); RI, 4.11 l/min (SD 0.48); P=0.78; n=5]. The lack of notable
      difference between the Vo2 peaks established at different WRpeak values in our
      RISE protocols provides the plateau criterion for verification of maximum Vo2 in
      a single test session, even when the data response profiles do not themselves
      evidence a plateau.

PMID- 16282429
TI  - Differential changes in muscle oxygenation between voluntary and stimulated
      isometric fatigue of human dorsiflexors.
AB  - The purpose of this study was to compare fatigue and recovery of maximal
      voluntary torque [maximal voluntary contraction (MVC)] and muscle oxygenation
      after voluntary (Vol) and electrically stimulated (ES) protocols of equal torque
      production. On 1 day, 10 male subjects [25 yr (SD 4)] completed a Vol fatigue
      protocol and, on a separate day, an ES fatigue protocol of the right
      dorsiflexors. Each task involved 2 min of intermittent (2-s on, 1-s off)
      isometric contractions at 50% of MVC. For the ES protocol, stimulation was
      delivered percutaneously to the common peroneal nerve at a frequency of 25 Hz.
      Compared with the Vol protocol, the ES protocol caused a greater impairment in
      MVC (75 vs. 83% prefatigue value; Pre) and greater increase in 50-Hz half
      relaxation time (165 vs. 117% Pre) postexercise. After acute (1 min) recovery,
      MVC impairment was similar for both protocols, whereas 50- Hz half relaxation
      time was still greater in the ES than Vol protocol. Total hemoglobin decreased to
      a similar extent in both protocols during exercise, but it was elevated above the
      resting value to a significantly greater extent for the ES protocol in recovery
      (18 vs. 11 microM). Oxygen saturation was significantly lower in the ES than Vol
      protocol during exercise (46 vs. 57% Pre), but it was significantly greater
      during recovery (120 vs. 105% Pre). These findings suggest that despite, equal
      torque production, ES contractions impose a greater metabolic demand on the
      muscle that leads to a transient greater impairment in MVC. The enforced
      synchronization and fixed frequency of excitation inherent to ES are the most
      likely causes for the exacerbated changes in the ES compared with the Vol
      protocol.

PMID- 16282430
TI  - Influence of gender and age on T-cell responses in a murine model of trauma
      hemorrhage: differences between circulating and tissue-fixed cells.
AB  - Clinical studies indicate that peripheral blood lymphocyte functions are
      depressed following trauma; however, it is unclear whether tissue-fixed
      lymphocyte functions are also altered under those conditions. Moreover, the
      impact of gender and age on peripheral T-cell responses following trauma
      hemorrhage (TH) are unknown. To study this, immature (approximately 3 wk of age),
      mature (approximately 7 wk of age), and aged (approximately 23 mo of age) male
      and proestrus female C3H/HeN mice were sham operated or subjected to trauma
      (i.e., midline laparotomy) and hemorrhagic shock (30+/-5 mmHg for 90 min). Twenty
      four hours after resuscitation, blood and splenocytes were harvested and T-cell
      functions assessed. In immature animals, TH induced an enhanced immune response
      in the splenic compartment and a suppressed response in the peripheral blood
      mononuclear cells (PBMC) that was independent of gender. Differential responses
      were observed in cells from mature mice. Splenic responses were enhanced
      following TH, independent of gender, whereas PBMC displayed gender dimorphism
      with suppressed proliferation and T-cell helper 1 responses in males but not in
      females. A similar pattern was observed in cells from aged mice. Splenic T cells
      from male mice displayed a suppressed CD4-to-CD8 ratio after TH, whereas no such
      change was observed in cells from proestrus females. In contrast, only PBMC from
      mature males displayed a suppressed CD4-to-CD8 ratio after TH. Thus gender
      differences exist in PBMC responses after TH that do not necessarily correlate
      with changes in the tissue-fixed compartment. Age is also an important factor in
      the immune responses after TH. In view of this, both gender and age should be
      taken into consideration in evaluating the immune status and in treatment of TH
      shock.

PMID- 16282431
TI  - Measuring airway exchange of endogenous acetone using a single-exhalation
      breathing maneuver.
AB  - Exhaled acetone is measured to estimate exposure or monitor diabetes and
      congestive heart failure. Interpreting this measurement depends critically on
      where acetone exchanges in the lung. Health professionals assume exhaled acetone
      originates from alveolar gas exchange, but experimental data and theoretical
      predictions suggest that acetone comes predominantly from airway gas exchange. We
      measured endogenous acetone in the exhaled breath to evaluate acetone exchange in
      the lung. The acetone concentration in the exhalate of healthy human subjects was
      measured dynamically with a quadrupole mass spectrometer and was plotted against
      exhaled volume. Each subject performed a series of breathing maneuvers in which
      the steady exhaled flow rate was the only variable. Acetone phase III had a
      positive slope (0.054+/-0.016 liter-1) that was statistically independent of flow
      rate. Exhaled acetone concentration was normalized by acetone concentration in
      the alveolar air, as estimated by isothermal rebreathing. Acetone concentration
      in the rebreathed breath ranged from 0.8 to 2.0 parts per million. Normalized end
      exhaled acetone concentration was dependent on flow and was 0.79+/-0.04 and
      0.85+/-0.04 for the slow and fast exhalation rates, respectively. A mathematical
      model of airway and alveolar gas exchange was used to evaluate acetone transport
      in the lung. By doubling the connective tissue (epithelium+mucosal tissue)
      thickness, this model predicted accurately (R2=0.94+/-0.05) the experimentally
      measured expirograms and demonstrated that most acetone exchange occurred in the
      airways of the lung. Therefore, assays using exhaled acetone measurements need to
      be reevaluated because they may underestimate blood levels.

PMID- 16282432
TI  - Comparison of postnatal lung growth and development between C3H/HeJ and C57BL/6J
      mice.
AB  - Previous work by our group has demonstrated substantial differences in lung
      volume and morphometric parameters between inbred mice. Specifically, adult
      C3H/HeJ (C3) have a 50% larger lung volume and 30% greater mean linear intercept
      than C57BL/6J (B6) mice. Although much of lung development occurs postnatally in
      rodents, it is uncertain at what age the differences between these strains become
      manifest. In this study, we performed quasi-static pressure-volume curves and
      morphometric analysis on neonatal mice. Lungs from anesthetized mice were
      degassed in vivo using absorption of 100% O2. Pressure-volume curves were then
      recorded in situ. The lungs were then fixed by instillation of Zenker's solution
      at a constant transpulmonary pressure. The left lung from each animal was used
      for morphometric determination of mean air space chord length (Lma). We found
      that the lung volume of C3 mice was substantially greater than that of B6 mice at
      all ages. In contrast, there was no difference in Lma (62.7 microm in C3 and 58.5
      microm in B6) of 3-day-old mice. With increasing age (8 days), there was a
      progressive decrease in the Lma of both strains, with the magnitude of the
      decrease in B6 Lma mice exceeding that of C3. C3 lung volume remained 50% larger.
      The combination of parenchymal architectural similarity with lung air volume
      differences and different rates of alveolar septation support the hypothesis that
      lung volume and alveolar dimensions are independently regulated.

PMID- 16282433
TI  - Neuromuscular fatigue development during maximal concentric and isometric knee
      extensions.
AB  - This study aimed to investigate mechanisms of neuromuscular fatigue during
      maximal concentric and isometric leg extensions inducing similar torque
      decrements. Nine physically active men performed two separate fatiguing sessions
      maintained until similar torque decreases were obtained. The first session, only
      conducted under isokinetic concentric conditions (CON), consisted of three series
      of 30 maximal voluntary concentric knee extensions (60 degrees/s). The second
      session, exclusively isometric (ISO), mimicked the torque decreases registered
      during the CON session while performing three long-lasting ISO contractions.
      Maximal voluntary torque, activation level (twitch interpolation technique),
      electromyographic activity (root mean square and median frequency) of the vastus
      lateralis muscle, and electrically evoked doublet-twitch mechanical properties
      were measured before and at the end of each of the three series. After the three
      series, similar torque decrements were obtained for both fatiguing procedures.
      The total fatiguing contraction durations were not different among procedures.
      With equivalent voluntary torque decrements, the doublet-twitch amplitude
      reduction was significantly greater (P<0.01) during the two first series of the
      CON procedure compared with ISO. No difference was observed for the third series.
      Although no difference was recorded with fatigue for median frequency changes
      between CON and ISO, activation levels and root mean square values demonstrated
      greater reductions (P<0.05) for all three series during the ISO procedure
      compared with CON. Performing CON or ISO fatiguing exercises demonstrated
      different fatigue origins. With CON exercises, peripheral fatigue developed
      first, followed by central fatigue, whereas with ISO exercises the fatigue
      pattern was inverted.

PMID- 16282434
TI  - Determinants of skin sympathetic nerve responses to isometric exercise.
AB  - Exercise-induced increases in skin sympathetic nerve activity (SSNA) are similar
      between isometric handgrip (IHG) and leg extension (IKE) performed at 30% of
      maximal voluntary contraction (MVC). However, the precise effect of exercise
      intensity and level of fatigue on this relationship is unclear. This study tested
      the following hypotheses: 1) exercise intensity and fatigue level would not
      affect the magnitude of exercise-induced increase in SSNA between IHG and IKE,
      and 2) altering IHG muscle mass would also not affect the magnitude of exercise
      induced increase in SSNA. In protocol 1, SSNA (peroneal microneurography) was
      measured during baseline and during the initial and last 30 s of isometric
      exercise to volitional fatigue in 12 subjects who randomly performed IHG and IKE
      bouts at 15, 30, and 45% MVC. In protocol 2, SSNA was measured in eight subjects
      who performed one-arm IHG at 30% MVC with the addition of IHG of the
      contralateral arm in 10-s intervals for 1 min. Exercise intensity significantly
      increased SSNA responses during the first 30 s of IHG (34+/-13, 70+/-11, and 92+/
      13% change from baseline) and IKE (30+/-17, 69+/-12, and 76+/-13% change from
      baseline) for 15, 30, and 45% MVC. During the last 30 s of exercise to volitional
      fatigue, there were no significant differences in SSNA between exercise
      intensities or limb. SSNA did not significantly change between one-arm and two
      arm IHG. Combined, these data indicate that exercise-induced increases in SSNA
      are intensity dependent in the initial portion of isometric exercise, but these
      differences are eliminated with the development of fatigue. Moreover, the
      magnitude of exercise-induced increase in SSNA responses is not dependent on
      either muscle mass involved or exercising limb.

PMID- 16282435
TI  - Effects of arterial hypotension on microvascular oxygen exchange in contracting
      skeletal muscle.
AB  - In healthy animals under normotensive conditions (N), contracting skeletal muscle
      perfusion is regulated to maintain microvascular O2 pressures (PmvO2) at levels
      commensurate with O2 demands. Hypovolemic hypotension (H) impairs muscle
      contractile function; we tested whether this condition would alter the matching
      of O2 delivery (Qo2) to O2 utilization (Vo2), as determined by PmvO2 at the onset
      of muscle contractions. PmvO2 in the spinotrapezius muscles of seven female
      Sprague-Dawley rats (280+/-6 g) was measured every 2 s across the transition from
      rest to 1-Hz twitch contractions. Measurements were made under N (mean arterial
      pressure, 97+/-4 mmHg) and H (induced by arterial section; mean arterial
      pressure, 58+/-3 mmHg, P<0.05) conditions; PmvO2 profiles were modeled using a
      multicomponent exponential fitted with independent time delays. Hypotension
      reduced muscle blood flow at rest (24+/-8 vs. 6+/-1 ml-1.min-1.100 g-1 for N and
      H, respectively; P<0.05) and during contractions (74+/-20 vs. 22+/-4 ml-1.min
      1.100 g-1 for N and H, respectively; P<0.05). H significantly decreased resting
      PmvO2 and steady-state contracting PmvO2(19.4+/-2.4 vs. 8.7+/-1.6 Torr for N and
      H, respectively, P<0.05). At the onset of contractions, H reduced the time delay
      (11.8+/-1.7 vs. 5.9+/-0.9 s for N and H, respectively, P<0.05) before the fall in
      PmvO2 and accelerated the rate of PmvO2 decrease (time constant, 12.6+/-1.4 vs.
      7.3+/-0.9 s for N and H, respectively, P<0.05). Muscle Vo2 was reduced by 71% at
      rest and 64% with contractions in H vs. N, and O2 extraction during H averaged
      78% at rest and 94% during contractions vs. 51 and 78% in N. These results
      demonstrate that H constrains the increase of skeletal muscle Qo2 relative to
      that of Vo2 at the onset of contractions, leading to a decreased PmvO2. According
      to Fick's law, this scenario will decrease blood-myocyte O2 flux, thereby slowing
      Vo2 kinetics and exacerbating the O2 deficit generated at exercise onset.

PMID- 16282436
TI  - Exogenous carbohydrate oxidation rates are elevated after combined ingestion of
      glucose and fructose during exercise in the heat.
AB  - The first purpose of this study was to investigate whether a glucose
      (GLU)+fructose (FRUC) beverage would result in a higher exogenous carbohydrate
      (CHO) oxidation rate and a higher fluid availability during exercise in the heat
      compared with an isoenergetic GLU beverage. A second aim of the study was to
      examine whether ingestion of GLU at a rate of 1.5 g/min during exercise in the
      heat would lead to a reduced muscle glycogen oxidation rate compared with
      ingestion of water (WAT). Eight trained male cyclists (maximal oxygen uptake:
      64+/-1 ml.kg-1.min-1) cycled on three different occasions for 120 min at 50%
      maximum power output at an ambient temperature of 31.9+/-0.1 degrees C. Subjects
      received, in random order, a solution providing either 1.5 g/min of GLU, 1.0
      g/min of GLU+0.5 g/min of FRUC, or WAT. Exogenous CHO oxidation during the last
      hour of exercise was approximately 36% higher (P<0.05) in GLU+FRUC compared with
      GLU, and peak oxidation rates were 1.14+/-0.05 and 0.77+/-0.08 g/min,
      respectively. Endogenous CHO oxidation was significantly lower (P<0.05) in
      GLU+FRUC compared with WAT. Muscle glycogen oxidation was not different after
      ingestion of GLU or WAT. Plasma deuterium enrichments were significantly higher
      (P<0.05) in WAT and GLU+FRUC compared with GLU. Furthermore, at 60 and 75 min of
      exercise, plasma deuterium enrichments were higher (P<0.05) in WAT compared with
      GLU+FRUC. Ingestion of GLU+FRUC during exercise in the heat resulted in higher
      exogenous CHO oxidation rates and fluid availability compared with ingestion of
      GLU and reduced endogenous CHO oxidation compared with ingestion of WAT.

PMID- 16282437
TI  - Ischemia-reperfusion injury changes the dynamics of Ca2+-contraction coupling due
      to inotropic drugs in isolated hearts.
AB  - Positive inotropic drugs may attenuate or exacerbate the deleterious effects of
      ischemia and reperfusion (IR) injury on excitation-contraction coupling in
      hearts. We 1) quantified the phase-space relationship between simultaneously
      measured myoplasmic Ca2+ concentration ([Ca2+]) and isovolumetric left
      ventricular pressure (LVP) using indexes of loop area, orientation, and position;
      and 2) quantified cooperativity by linearly modeling the phase-space relationship
      between [Ca2+] and rate of LVP development in intact hearts during administration
      of positive inotropic drugs before and after global IR injury. Unpaced, isolated
      guinea pig hearts were perfused at a constant pressure with Krebs-Ringer solution
      (37 degrees C, 1.25 mM CaCl2). [Ca2+] was measured ratiometrically by indo 1
      fluorescence by using a fiber-optic probe placed at the left ventricular free
      wall. LVP was measured by using a saline-filled latex balloon and transducer.
      Drugs were infused for 2 min, 30 min before, and for 2 min, 30 min after 30-min
      global ischemia. IR injury worsened Ca2+-contraction coupling, as seen from
      decreased orientation and repositioning of the loop rightward and downward and
      reduced cooperativity of contraction and relaxation with or without drugs.
      Dobutamine (4 microM) worsened, whereas dopamine (8 microM) improved Ca2+
      contraction coupling before and after IR injury. Dobutamine and dopamine improved
      cooperativity of contraction and relaxation after IR injury, whereas only
      dopamine increased cooperativity of relaxation before IR injury. Digoxin (1
      microM) improved Ca2+-contraction coupling and cooperativity of contraction after
      but not before ischemia. Levosimendan (1 microM) did not alter Ca2+-contraction
      coupling or cooperativity, despite producing concomitant increases in
      contractility, relaxation, and Ca2+ flux before and after ischemia. Dynamic
      indexes based on LVP-[Ca2+] diagrams (area, shape, position) can be used to
      identify and measure alterations in Ca2+-contraction coupling during
      administration of positive inotropic drugs in isolated hearts before and after IR
      injury.

PMID- 16282438
TI  - Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells
      leads to malignant transformation.
AB  - Despite recent emerging evidence suggesting that cancer stem cells subsist in a
      variety of tumors, it is not yet fully elucidated whether postnatal stem cells
      are directly involved in tumorigenesis. We used murine bone marrow-derived
      mesenchymal stem cells (BMMSCs) as a model to test a hypothesis that
      tumorigenesis may originate from spontaneous mutation of stem cells. In this
      study, we demonstrated that murine BMMSCs, after numerous passages, obtained
      unlimited population doublings and proceeded to a malignant transformation state,
      resulting in fibrosarcoma formation in vivo. Transformed BMMSCs colonized to
      multiple organs when delivered systemically through the tail vein. Fibrosarcoma
      cells formed by transformed BMMSCs contained cancer progenitors, which were
      capable of generating colony clusters in vitro and fibrosarcoma in vivo by the
      second administration. The mechanism by which BMMSCs transformed to malignant
      cells was associated with accumulated chromosomal abnormalities, gradual
      elevation in telomerase activity, and increased c-myc expression. Moreover,
      BMMSCs and their transformed counterpart, fibrosarcoma-forming cells,
      demonstrated different sensitivity to anti-cancer drugs. BMMSCs/fibrosarcoma
      transformation system may provide an ideal system to elucidate the mechanism of
      how stem cells become cancer cells and to screen anti-sarcoma drugs.

PMID- 16282439
TI  - Nucleostemin is a marker of proliferating stromal stem cells in adult human bone
      marrow.
AB  - The identification of stem cell-specific proteins and the elucidation of their
      novel regulatory pathways may help in the development of protocols for control of
      their self-renewal and differentiation for cell-based therapies. Nucleostemin is
      a recently discovered nucleolar protein predominantly associated with
      proliferating rat neural and embryonic stem cells, and some human cancer cell
      lines. A comprehensive study of nucleostemin in human adult bone marrow stem
      cells is lacking. The aim of the study was to determine if nucleostemin is
      synthesized by adult bone marrow stem cells and to analyze its expression during
      their expansion and differentiation. Using a multipotential adherent population
      of stem cells, nucleostemin was localized to the nucleoli and occurred in 43.3%
      of the cells. There was a high level of expression of nucleostemin mRNA in bone
      marrow stem cells and this remained unchanged over time during cell expansion in
      culture. When bone marrow stem cells were stimulated to proliferate by fibroblast
      growth factor (FGF)-2, nucleostemin expression increased in a dose-dependent
      manner. Small interfering RNA (siRNA) knockdown of nucleostemin abolished the
      proliferative effect of FGF-2. When bone marrow stem cells were differentiated
      into chondrocytes, adipocytes, or osteocytes, nucleostemin expression was 70%-90%
      lower than in the undifferentiated cells retained in monolayer culture. We
      conclude that nucleostemin is a marker of undifferentiated human adult bone
      marrow stem cells and that it is involved in the regulation of proliferation of
      these cells.

PMID- 16282440
TI  - In vivo formation of unstable heterokaryons after liver damage and hematopoietic
      stem cell/progenitor transplantation.
AB  - Following reports of lineage plasticity in human hematopoietic stem cells (HSCs),
      we investigated the potential of human cord blood HSC-enriched cells to create
      hepatocytes in hosts after inducing liver damage. Carbon tetrachloride induces
      severe liver damage and subsequent repair via mitosis of resident hepatocytes. It
      additionally leads to a threefold increase in homing of human mononuclear cells
      to bone marrow and liver and subsequently to a substantial enhancement of bone
      marrow engraftment. Eight weeks after liver damage and infusion of an enhanced
      green fluorescent protein (eGFP) lentivirus-transduced human HSC-enriched cell
      population, we observed eGFP-positive cells with clear hepatocyte morphology in
      the livers of animals. These eGFP-positive cells co-expressed human albumin, and
      reverse-transcription polymerase chain reaction (PCR) analysis demonstrated the
      presence of human albumin and alpha-anti-trypsin mRNA. However, two antibodies
      against human mitochondria and human nuclei failed to mark eGFP-positive
      hepatocyte-like cells but did give clear staining of donor-derived hematopoietic
      cells. Subsequent fluorescent in situ hybridization (FISH) analysis revealed the
      presence of mouse Y chromosome in eGFP-positive hepatocyte-like cells. To resolve
      this discrepancy, we performed single-cell PCR analysis of microdissected eGFP
      positive hepatocyte-like cells and found that they contained mostly mouse and
      little human genomic material. FISH analysis highlighting the centromeres of all
      human chromosomes revealed only few human chromosomes in these cells. From these
      results, we conclude that similar to their murine counterparts, human
      hematopoietic cells have the potential to fuse with resident host hepatocytes.
      Because no selective pressure is applied to retain the human genomic material, it
      is gradually lost over time, leading to a variable phenotype of the chimeric
      cells and making their detection difficult.

PMID- 16282442
TI  - Transcriptional profiling of mammary gland side population cells.
AB  - Similar to the bone marrow, the mammary gland contains a distinct population of
      Hoechst-effluxing side population cells, mammary gland side population cells (MG
      SPs). To better characterize MG-SPs, their microarray gene profiles were compared
      to the remaining cells, which retain Hoechst dye (mammary gland non-side
      population cells [MG-NSPs]). For analysis, Gene Ontology (GO) that describes
      genes in terms of biological processes and Ontology Traverser (OT) that performs
      enrichment analysis were used. OT showed that MG-SP-specific genes were enriched
      in the GO categories of cell cycle regulation and checkpoints, multidrug
      resistant transporters, organogenesis, and vasculogenesis. The MG-NSP-upregulated
      genes were enriched in the GO category of cellular organization and biogenesis,
      which includes basal epithelial markers, p63, smooth muscle actin, myosin, alpha6
      integrin, cytokeratin (CK) 14, and luminal markers CK8 and CD24. Additional
      studies showed that a higher percentage of MG-SPs exist in the G1 phase of the
      cell cycle compared with the MG-NSPs. G1 cell cycle block of MG-SPs may be
      explained by higher expression of cell cycle-negative regulatory genes such as
      transforming growth factor-beta2, insulin-like growth factor binding protein-5,
      P18(INK4C), and wingless-5a (Wnt-5a). Accordingly, a smaller percentage of MG-SPs
      expressed nuclear beta-catenin, possibly as a consequence of the higher
      expression of Wnt-5a. In conclusion, microarray gene profiling suggests that MG
      SPs are a lineage-deficient mammary gland subpopulation expressing key genes
      involved in cell cycle regulation, development, and angiogenesis.

PMID- 16282441
TI  - Integrins in slow-cycling corneal epithelial cells at the limbus in the mouse.
AB  - Adult corneal epithelial stem cells (CESCs) have been shown to reside at the
      periphery of the cornea at a site called the corneoscleral junction or limbus.
      Although studies have shown that these cells are slow cycling, their molecular
      characteristics are not well understood. Using a whole-mount procedure, we show
      that whereas alpha9-integrin is present in a subset of the basal cells at the
      corneal limbus and absent in the central cornea, beta1-, beta4-, alpha3-, and
      alpha6-integrins are more highly expressed overall in central corneal basal
      cells. To characterize CESCs based on their slow-cycling nature, we
      simultaneously evaluated 5-bromo-2-deoxyuridine (BrdU) label-retaining cells
      (LRCs) and integrin expression (alpha9, beta1, and beta4) in a total of 1,889
      cells at the limbus of adult mice that had been injected as neonates with BrdU.
      Whereas the LRCs were usually observed adjacent to alpha9-integrin-positive
      cells, most LRCs were alpha9-integrin-negative and expressed high levels of beta1
      and beta4-integrin. In addition, we observed more BrdU-positive LRCs at the
      superior and inferior quadrants of adult mouse corneas than at the nasal and
      temporal quadrants, and determined that 0.94 to 3.6% of the limbal basal cells
      were slow cycling. We conclude from these data that the slow-cycling LRCs in the
      adult mouse cornea are enriched in cells that express high levels of beta1- and
      beta4-integrin and little alpha9-integrin.

PMID- 16282443
TI  - Epigenetic modification is central to genome reprogramming in somatic cell
      nuclear transfer.
AB  - The recent high-profile reports of the derivation of human embryonic stem cells
      (ESCs) from human blastocysts produced by somatic cell nuclear transfer (SCNT)
      have highlighted the possibility of making autologous cell lines specific to
      individual patients. Cell replacement therapies have much potential for the
      treatment of diverse conditions, and differentiation of ESCs is highly desirable
      as a means of producing the ranges of cell types required. However, given the
      range of immunophenotypes of ESC lines currently available, rejection of the
      differentiated cells by the host is a potentially serious problem. SCNT offers a
      means of circumventing this by producing ESCs of the same genotype as the donor.
      However, this technique is not without problems because it requires resetting of
      the gene expression program of a somatic cell to a state consistent with
      embryonic development. Some remodeling of parental DNA does occur within the
      fertilized oocyte, but the somatic genome presented in a radically different
      format to those of the gametes. Hence, it is perhaps unsurprising that many genes
      are expressed aberrantly within "cloned" embryos and the ESCs derived from them.
      Epigenetic modification of the genome through DNA methylation and covalent
      modification of the histones that form the nucleosome is the key to the
      maintenance of the differentiated state of the cell, and it is this that must be
      reset during SCNT. This review focuses on the mechanisms by which this is
      achieved and how this may account for its partial failure in the "cloning"
      process. We also highlight the potential dangers this may introduce into ESCs
      produced by this technology.

PMID- 16282444
TI  - Basic fibroblast growth factor support of human embryonic stem cell self-renewal.
AB  - Human embryonic stem (ES) cells have most commonly been cultured in the presence
      of basic fibroblast growth factor (FGF2) either on fibroblast feeder layers or in
      fibroblast-conditioned medium. It has recently been reported that elevated
      concentrations of FGF2 permit the culture of human ES cells in the absence of
      fibroblasts or fibroblast-conditioned medium. Herein we compare the ability of
      unconditioned medium (UM) supplemented with 4, 24, 40, 80, 100, and 250 ng/ml
      FGF2 to sustain low-density human ES cell cultures through multiple passages. In
      these stringent culture conditions, 4, 24, and 40 ng/ml FGF2 failed to sustain
      human ES cells through three passages, but 100 ng/ml sustained human ES cells
      with an effectiveness comparable to conditioned medium (CM). Two human ES cell
      lines (H1 and H9) were maintained for up to 164 population doublings (7 and 4
      months) in UM supplemented with 100 ng/ml FGF2. After prolonged culture, the
      cells formed teratomas when injected into severe combined immunodeficient beige
      mice and expressed markers characteristic of undifferentiated human ES cells. We
      also demonstrate that FGF2 is degraded more rapidly in UM than in CM, partly
      explaining the need for higher concentrations of FGF2 in UM. These results
      further facilitate the large-scale, routine culture of human ES cells and suggest
      that fibroblasts and fibro-blast-conditioned medium sustain human ES cells in
      part by stabilizing FGF signaling above a critical threshold.

PMID- 16282445
TI  - Human side population keratinocytes exhibit long-term proliferative potential and
      a specific gene expression profile and can form a pluristratified epidermis.
AB  - The aim of the present study was to characterize human side population (SP)
      epidermal keratinocytes isolated from primary cell cultures. For that purpose,
      keratinocytes were isolated from normal adult breast skin samples and the Hoechst
      33342 exclusion assay described for hematopoietic cells was adapted to
      keratinocytes. Three types of keratinocytes were studied: the SP, the main
      population (MP), and the unsorted initial population. SP keratinocytes
      represented 0.16% of the total population. In short-term cultures, they exhibited
      an increased colony-forming efficiency and produced more actively growing
      colonies than did unsorted and MP keratinocytes. In long-term cultures, SP cells
      exhibited an extensive expansion potential, performing a mean of 44 population
      doublings for up to 12 successive passages after cell sorting. Moreover, even in
      long-term cultures, SP keratinocytes were able to form a pluristratified
      epidermis when seeded on a dermal substrate. Unsorted and MP keratinocytes
      promoted a reduced expansion: mean values of 14 population doublings for five
      passages and 12 population doublings for four successive passages, respectively.
      To further characterize SP cells, cDNA microarrays were used to identify their
      molecular signature. Transcriptome profiling showed that 41 genes were
      differentially expressed in SP (vs. MP) cells, with 37 upregulated genes and only
      four downregulated genes in SP cells. The majority of these genes were
      functionally related to the regulation of transcription and cell signaling. In
      conclusion, SP human keratinocytes isolated from primary cultures exhibited both
      short- and long-term high proliferative potential, formed a pluristratified
      epidermis, and were characterized by a specific gene expression profile.

PMID- 16282446
TI  - Human T-cell leukemia virus type 1 expressing nonoverlapping tax and rex genes
      replicates and immortalizes primary human T lymphocytes but fails to replicate
      and persist in vivo.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus associated
      primarily with adult T-cell leukemia and neurological disease. HTLV-1 encodes the
      positive trans-regulatory proteins Tax and Rex, both of which are essential for
      viral replication. Tax activates transcription initiation from the viral long
      terminal repeat and modulates the transcription or activity of a number of
      cellular genes. Rex regulates gene expression posttranscriptionally by
      facilitating the cytoplasmic expression of incompletely spliced viral mRNAs. Tax
      and Rex mutants have been identified that have defective activities or impaired
      biochemical properties associated with their function. To ultimately determine
      the contribution of specific protein activities on viral replication and cellular
      transformation of primary T cells, mutants need to be characterized in the
      context of an infectious molecular clone. Since the tax and rex genes are in
      partially overlapping reading frames, mutation in one gene frequently disrupts
      the other, confounding interpretation of mutational analyses in the context of
      the virus. Here we generated and characterized a unique proviral clone (H1IT) in
      which the tax and rex genes were separated by expressing Tax from an internal
      ribosome entry site. We showed that H1IT expresses both functional Tax and Rex.
      In short- and long-term coculture assays, H1IT was competent to infect and
      immortalize primary human T cells similar to wild-type HTLV-1. In contrast, H1IT
      failed to efficiently replicate and persist in inoculated rabbits, thus
      emphasizing the importance of temporal and quantitative regulation of specific
      mRNA for viral survival in vivo.

PMID- 16282447
TI  - Endocytosis and a low-pH step are required for productive entry of equine
      infectious anemia virus.
AB  - Recently, it has become evident that entry of some retroviruses into host cells
      is dependent upon a vesicle-localized, low-pH step. The entry mechanism of equine
      infectious anemia virus (EIAV) has yet to be examined. Here, we demonstrate that
      wild-type strains of EIAV require a low-pH step for productive entry.
      Lysosomotropic agents that inhibit the acidification of internal vesicles
      inhibited productive entry of EIAV. The presence of ammonium chloride (30 mM),
      monensin (30 microM), or bafilomycin A (50 nM) in the medium dramatically
      decreased the number of EIAV antigen-positive cells. We found that a low-pH step
      was required for EIAV infection of tissue culture cell lines as well as primary
      cells, such as endothelial cells and monocyte-derived macrophages. The ammonium
      chloride treatment did not reduce virion stability, nor did the treatment prevent
      virion binding to cells. Consistent with a requirement for a low-pH step, virion
      infectivity was enhanced more than threefold by brief low-pH treatment following
      binding of viral particles to permissive cells. A superinfecting variant strain
      of EIAV, vMA-1c, did not require a low-pH step for productive infection of
      fibroblasts. However, lysosomotropic agents were inhibitory to vMA-1c infection
      in the other cell types that vMA-1c infected but did not superinfect, indicating
      that the entry pathway used by vMA-1c for superinfection abrogates the need for
      the low-pH step.

PMID- 16282448
TI  - Receptor-mediated entry by equine infectious anemia virus utilizes a pH-dependent
      endocytic pathway.
AB  - Previous studies of human and nonhuman primate lentiviral entry mechanisms
      indicate a predominant use of pH-independent pathways, although more recent
      studies of human immunodeficiency virus type 1 entry appear to reveal the use of
      a low-pH-dependent entry pathway in certain target cells. To expand the
      characterization of the specificity of lentiviral entry mechanisms, we have in
      the current study examined the entry pathway of equine infectious anemia virus
      (EIAV) during infection of its natural target, equine macrophages, permissive
      equine fibroblastic cell lines, and an engineered mouse cell line expressing the
      recently defined equine lentivirus receptor-1. The specificity of EIAV entry into
      these various cells was determined by assaying the effects of specific drug
      treatments on the level of virus entry as measured by quantitative real-time PCR
      assay of early reverse transcripts or by measurements of virion production. The
      results of these studies demonstrated that EIAV entry into all cell types was
      substantially inhibited in a dose-dependent manner by treatment with the vacuolar
      H+-ATPase inhibitors concanamycin A and bafilomycin A1 or the lysosomotropic weak
      base ammonium chloride. In contrast, treatments with sucrose to block clathrin
      mediated endocytosis or with chloroquine to block organelle acidification failed
      to inhibit EIAV entry into the same target cells. The observed inhibition of EIAV
      entry was shown not to be related to cytotoxicity. Taken together, these
      experiments reveal for the first time that EIAV receptor-mediated entry into
      target cells is via a low-pH-dependent endocytic pathway.

PMID- 16282449
TI  - Analysis of human immunodeficiency virus type 1 Gag dimerization-induced
      assembly.
AB  - The nucleocapsid (NC) domains of retrovirus precursor Gag (PrGag) proteins play
      an essential role in virus assembly. Evidence suggests that NC binding to viral
      RNA promotes dimerization of PrGag capsid (CA) domains, which triggers assembly
      of CA N-terminal domains (NTDs) into hexamer rings that are interconnected by CA
      C-terminal domains. To examine the influence of dimerization on human
      immunodeficiency virus type 1 (HIV-1) Gag protein assembly in vitro, we analyzed
      the assembly properties of Gag proteins in which NC domains were replaced with
      cysteine residues that could be linked via chemical treatment. In accordance with
      the model that Gag protein pairing triggers assembly, we found that cysteine
      cross-linking or oxidation reagents induced the assembly of virus-like particles.
      However, efficient assembly also was observed to be temperature dependent or
      required the tethering of NTDs. Our results suggest a multistep pathway for HIV-1
      Gag protein assembly. In the first step, Gag protein pairing through NC-RNA
      interactions or C-terminal cysteine linkage fosters dimerization. Next, a
      conformational change converts assembly-restricted dimers or small oligomers into
      assembly-competent ones. At the final stage, final particle assembly occurs,
      possibly through a set of larger intermediates.

PMID- 16282450
TI  - Akt/protein kinase B activation by adenovirus vectors contributes to NFkappaB
      dependent CXCL10 expression.
AB  - In gene therapy, the innate immune system is a significant barrier to the
      effective application of adenovirus (Ad) vectors. In kidney epithelium-derived
      (REC) cells, serotype 5 Ad vectors induce the expression of the chemokine CXCL10
      (IP-10), a response that is dependent on NFkappaB. Compared to the parental
      vector AdLuc, transduction with the RGD-deleted vector AdL.PB resulted in reduced
      CXCL10 activation despite increasing titers, implying that RGD-alpha(V) integrin
      interactions contribute to adenovirus induction of inflammatory genes. Akt, a
      downstream effector of integrin signaling, was activated within 10 min of
      transduction with Ad vectors in a dose-dependent manner. Akt activation was not
      present following transduction with AdL.PB, confirming the importance of capsid
      alpha(V) integrin interactions in Ad vector Akt activation. Inhibition of the
      phosphoinositide-3-OH kinase/Akt pathway by Wortmannin or Ly294002 compounds
      decreased Ad vector induction of CXCL10 mRNA. Similarly, adenovirus-mediated
      overexpression of the dominant negative AktAAA decreased CXCL10 mRNA expression
      compared to the reporter vector AdLacZ alone. The effect of Akt on CXCL10 mRNA
      expression occurred via NFkappaB-dependent transcriptional activation, since
      AktAAA overexpression and Ly294002 both inhibited CXCL10 and NFkappaB promoter
      activation in luciferase reporter experiments. These results show that Akt plays
      a role in the Ad vector activation of NFkappaB and CXCL10 expression.
      Understanding the mechanism underlying the regulation of host immunomodulatory
      genes by adenovirus vectors will lead to strategies that will improve the
      efficacy and safety of these agents for clinical use.

PMID- 16282451
TI  - Herpes simplex virus 1 immediate-early and early gene expression during
      reactivation from latency under conditions that prevent infectious virus
      production.
AB  - The program of gene expression exhibited by herpes simplex virus during
      productive infection of cultured cells is well established; however, less is
      known about the regulatory controls governing reactivation from latency in
      neurons. One difficulty in examining gene regulation during reactivation lies in
      distinguishing between events occurring in initial reactivating cells versus
      events occurring in secondarily infected cells. Thus, two inhibitors were
      employed to block production of infectious virus: acyclovir, which inhibits viral
      DNA synthesis, and WAY-150138, which permits viral DNA synthesis but inhibits
      viral DNA encapsidation. Latently infected murine ganglia were explanted in the
      presence of either inhibitor, and then amounts of RNA, DNA, or infectious virus
      were quantified. In ganglia explanted for 48 h, the levels of five immediate
      early and early RNAs did not exhibit meaningful differences between acyclovir and
      WAY-150138 treatments when analyzed by in situ hybridization or quantitative
      reverse transcription-PCR. However, comparative increases in viral DNA and RNA
      content in untreated ganglia suggested that virus was produced before 48 h
      postexplant. This was confirmed by the detection of infectious virus as early as
      14 h postexplant. Together, these results suggest that high levels of viral gene
      expression at 48 h postexplant are due largely to the production of infectious
      virus and subsequent spread through the tissue. These results lead to a
      reinterpretation of previous results indicating a role for DNA replication in
      immediate-early and early viral gene expression; however, it remains possible
      that viral gene expression is regulated differently in neurons than in cultured
      cells.

PMID- 16282452
TI  - Interaction of rotavirus with human myeloid dendritic cells.
AB  - We have previously shown that very few rotavirus (RV)-specific T cells that
      secrete gamma interferon circulate in recently infected and seropositive adults
      and children. Here, we have studied the interaction of RV with myeloid immature
      (IDC) and mature dendritic cells (MDC) in vitro. RV did not induce cell death of
      IDC or MDC and induced maturation of between 12 and 48% of IDC. Nonetheless, RV
      did not inhibit the maturation of IDC or change the expression of maturation
      markers on MDC. After treatment with RV, few IDC expressed the nonstructural
      viral protein NSP4. In contrast, a discrete productive viral infection was shown
      in MDC of a subset of volunteers, and between 3 and 46% of these cells expressed
      NSP4. RV-treated IDC secreted interleukin 6 (IL-6) (but not IL-1beta, IL-8, IL
      10, IL-12, tumor necrosis factor alpha, or transforming growth factor beta), and
      MDC released IL-6 and small amounts of IL-10 and IL-12p70. The patterns of
      cytokines secreted by T cells stimulated by staphylococcal enterotoxin B
      presented by MDC infected with RV or uninfected were comparable. The frequencies
      and patterns of cytokines secreted by memory RV-specific T cells evidenced after
      stimulation of peripheral blood mononuclear cells (PBMC) with RV were similar to
      those evidenced after stimulation of PBMC with RV-infected MDC. Finally, IDC
      treated with RV strongly stimulated naive allogeneic CD4+ T cells to secrete Th1
      cytokines. Thus, although RV does not seem to be a strong maturing stimulus for
      DC, it promotes their capacity to prime Th1 cells.

PMID- 16282453
TI  - Envelope is a major viral determinant of the distinct in vitro cellular
      transformation tropism of human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are related
      deltaretroviruses but are distinct in their disease-inducing capacity. These
      viruses can infect a variety of cell types, but only T lymphocytes become
      transformed, which is defined in vitro as showing indefinite interleukin-2
      independent growth. Studies have indicated that HTLV-1 has a preferential tropism
      for CD4+ T cells in vivo and is associated with the development of leukemia and
      neurological disease. Conversely, the in vivo T-cell tropism of HTLV-2 is less
      clear, although it appears that CD8+ T cells preferentially harbor the provirus,
      with only a few cases of disease association. The difference in T-cell
      transformation tropism has been confirmed in vitro as shown by the preferential
      transformation of CD4+ T cells by HTLV-1 versus the transformation of CD8+ T
      cells by HTLV-2. Our previous studies showed that Tax and overlapping Rex do not
      confer the distinct T-cell transformation tropisms between HTLV-1 and HTLV-2.
      Therefore, for this study HTLV-1 and HTLV-2 recombinants were generated to assess
      the contribution of LTR and env sequences in T-cell transformation tropism. Both
      sets of proviral recombinants expressed p19 Gag following transfection into
      cells. Furthermore, recombinant viruses were replication competent and had the
      capacity to transform T lymphocytes. Our data showed that exchange of the env
      gene resulted in altered T-cell transformation tropism compared to wild-type
      virus, while exchange of long terminal repeat sequences had no significant
      effect. HTLV-2/Env1 preferentially transformed CD4+ T cells similarly to wild
      type HTLV-1 (wtHTLV-1), whereas HTLV-1/Env2 had a transformation tropism similar
      to that of wtHTLV-2 (CD8+ T cells). These results indicate that env is a major
      viral determinant for HTLV T-cell transformation tropism in vitro and provides
      strong evidence implicating its contribution to the distinct pathogenesis
      resulting from HTLV-1 versus HTLV-2 infections.

PMID- 16282455
TI  - The AAUAAA motif of bamboo mosaic virus RNA is involved in minus-strand RNA
      synthesis and plus-strand RNA polyadenylation.
AB  - Bamboo mosaic virus (BaMV) has a single-stranded positive-sense RNA genome with a
      5'-cap structure and a 3' poly(A) tail. Deleting the internal loop that contains
      the putative polyadenylation signal (AAUAAA) in the 3' untranslated region (UTR)
      of BaMV genomic RNA appeared to diminish coat protein accumulation to 2% (C. P.
      Cheng and C. H. Tsai, J. Mol. Biol. 288:555-565, 1999). To investigate the
      function of the AAUAAA motif, mutations were introduced into an infectious BaMV
      cDNA at each residue except the first nucleotide. After transfection of Nicotiana
      benthamiana protoplasts with RNA transcript, the accumulations of viral coat
      protein and RNAs were determined. Based on the results, three different
      categories could be deduced for the mutants. Category 1 includes two mutants
      expressing levels of the viral products similar to those of the wild-type virus.
      Six mutations in category 2 led to decreased to similar levels of both minus
      strand and genomic RNAs. Category 3 includes the remaining seven mutations that
      also bring about decreases in both minus- and plus-strand RNA levels, with more
      significant effects on genomic RNA accumulation. Mutant transcripts from each
      category were used to infect N. benthamiana plants, from which viral particles
      were isolated. The genomic RNAs of mutants in category 3 were found to have
      shorter poly(A) tails. Taken together, the results suggest that the AAUAAA motif
      in the 3' UTR of BaMV genomic RNA is involved not only in the formation of the
      poly(A) tail of the plus-strand RNA, but also in minus-strand RNA synthesis.

PMID- 16282454
TI  - Clearance of herpes simplex virus type 2 by CD8+ T cells requires gamma
      interferon and either perforin- or Fas-mediated cytolytic mechanisms.
AB  - The T-cell-mediated resolution of herpes simplex virus type 2 (HSV-2) genital
      infections is not fully understood. In these studies, the mechanisms by which
      CD8+ T cells clear virus from the genital epithelium were examined. Ovalbumin
      (OVA)-specific CD8+ T cells from OT-I transgenic mice cleared a thymidine kinase
      deficient, ovalbumin-expressing HSV-2 virus (HSV-2 tk- OVA) from the genital
      epithelium of recipient mice, and clearance was abrogated by in vivo
      neutralization of gamma interferon (IFN-gamma). Further, CD8+ OT-I T cells
      deficient in IFN-gamma were unable to clear HSV-2 tk- OVA from the vaginal
      epithelium. The requirement for cytolytic mechanisms in HSV-2 tk- OVA clearance
      was tested in radiation chimeras by adoptive transfer of wild-type or perforin
      deficient OT-I T cells to irradiated Fas-defective or wild-type recipients.
      Although a dramatic decrease in viral load was observed early after challenge
      with HSV-2 tk- OVA, full resolution of the infection was not achieved in
      recipients lacking both perforin- and Fas-mediated cytolytic pathways. These
      results suggest that IFN-gamma was responsible for an early rapid decrease in HSV
      2 virus titer. However, either perforin- or Fas-mediated cytolytic mechanisms
      were required to achieve complete clearance of HSV-2 from the genital epithelium.

PMID- 16282456
TI  - Protection from interferon-induced apoptosis by Epstein-Barr virus small RNAs is
      not mediated by inhibition of PKR.
AB  - The Epstein-Barr virus (EBV) EBER transcripts are small, highly structured RNAs
      able to bind to and inhibit activation of the double-stranded RNA-dependent
      protein kinase PKR in cell-free systems, and within latently infected B-cell
      lines they inhibit alpha interferon-induced apoptosis that is believed to be
      mediated through PKR. Here, we address the consequences of EBER expression for
      PKR activation in vivo in response to alpha interferon. In agreement with
      published findings, either EBV infection or the EBERs alone protected Burkitt
      lymphoma cells from alpha-interferon-induced apoptosis. However, utilizing
      multiple phosphorylation state-specific antibodies to monitor PKR activation
      within cells in response to interferon, we demonstrate that the EBERs are unable
      to inhibit phosphorylation of either cytoplasmic or nuclear PKR. Concordantly, a
      direct substrate of PKR, the alpha subunit of eukaryotic initiation factor 2 (eIF
      2alpha), was equally phosphorylated in EBV-positive and EBV-negative cells
      following interferon treatment. Therefore, EBER inhibition of alpha-interferon
      induced apoptosis, and potentially other PKR-mediated events, is unlikely to be
      mediated through direct inhibition of PKR, as previously thought.

PMID- 16282457
TI  - Effect of mutations in the mouse hepatitis virus 3'(+)42 protein binding element
      on RNA replication.
AB  - The mouse hepatitis virus (MHV) genome's 3' untranslated region contains cis
      acting sequences necessary for replication. Studies of MHV and other
      coronaviruses have indicated a role for RNA secondary and tertiary elements in
      replication. Previous work in our laboratory has identified four proteins which
      form ribonucleoprotein complexes with the 3'-terminal 42 nucleotides [3'(+)42] of
      the MHV genome. Defective interfering (DI) RNA replication assays have
      demonstrated a role for the 3'(+)42 host protein binding element in the MHV life
      cycle. Using gel mobility shift RNase T1 protection assays and secondary
      structure modeling, we have characterized a possible role for RNA secondary
      structure in host protein binding to the 3'-terminal 42-nucleotide element.
      Additionally we have identified a role for the 3'-terminal 42-nucleotide host
      protein binding element in RNA replication and transcription using DI RNA
      replication assays and targeted recombination and by directly constructing
      mutants in this protein binding element using a recently described MHV reverse
      genetic system. DI RNA replication assays demonstrated that mutations in the
      3'(+)42 host protein binding element had a deleterious effect on the accumulation
      of DI RNA. When the identical mutations were directly inserted into the MHV
      genome, most mutant genomes were viable but formed smaller plaques than the wild
      type parent virus. One mutant was not viable. This mutant directed the synthesis
      of genome-sized negative-sense RNA approximately as efficiently as the wild type
      did but had a defect in subgenomic mRNA synthesis. These results point to a
      potential role for sequences at the extreme 3' end of the MHV genome in
      subgenomic RNA synthesis.

PMID- 16282458
TI  - Resistance to friend virus-induced erythroleukemia in W/W(v) mice is caused by a
      spleen-specific defect which results in a severe reduction in target cells and a
      lack of Sf-Stk expression.
AB  - The characteristic progression and specificity of Friend virus for the erythroid
      lineage have allowed for the identification of a number of host-encoded loci that
      are required for disease progression. Several of these loci, including the Friend
      virus susceptibility gene 2 (Fv2), dominant white spotting gene (W), and Steel
      gene (Sl), regulate the initial polyclonal expansion of infected erythroid
      progenitor cells. W and Sl encode the Kit receptor tyrosine kinase and its
      ligand, stem cell factor, respectively. W mutant mice are severely anemic, and
      earlier work suggested that this defect in erythroid differentiation is the cause
      for the resistance to Friend virus-induced erythroleukemia. Here we show that in
      bone marrow, W/W(v) mice have near normal numbers of target cells and the initial
      infection of bone marrow occurs normally in vivo. In contrast, spleen cells from
      W/W(v) mice infected both in vitro and in vivo with Friend virus failed to give
      rise to erythropoietin-independent colonies at any time following Friend virus
      infection, suggesting that mutation of the Kit receptor specifically affects
      target cells in the spleen, rendering the mutant mice resistant to the
      development of Friend virus-induced erythroleukemia. In addition, we show that
      the Kit+ pathogenic targets of Friend virus in the spleen are distinct from the
      pathogenic targets in bone marrow and this population of spleen target cells is
      markedly decreased in W/W(v) mice and these cells fail to express Sf-Stk. These
      results also underscore the unique nature of the spleen microenvironment in its
      role in supporting the progression of acute leukemia in Friend virus-infected
      mice.

PMID- 16282459
TI  - Frequency, proliferation, and activation of human memory T cells induced by a
      nonhuman adenovirus.
AB  - Multiple human adenovirus (HAd) infections during childhood generate a memory T
      cell (T(M)) response, which is the primary defense against HAd-induced morbidity.
      This cellular memory creates a conundrum for the potential clinical use of HAd
      derived vectors: vector-mediated gene transfer is efficient in immunologically
      naive mammals but will be compromised by memory immunity when using vectors
      derived from ubiquitous human pathogens. The potential lack of cellular and
      humoral memory is one reason we developed vectors from canine adenovirus serotype
      2 (CAV-2). Here, we assayed human peripheral blood mononuclear cells for a T(M)
      response that could be stimulated by CAV-2 virion and individual capsid proteins.
      We found that less than half of the donors harbored a proliferating T(M) response
      directed against the CAV-2 virion (versus >85% against HAd5) in spite of a
      conserved antigenic Adenoviridae epitope in the CAV-2 hexon. When CAV-2 induced
      proliferation, it was 2.3- to >10-fold lower than HAd5 depending on the assay.
      The primary proliferating cells appeared to be memory (CD45RO+) CD4+ lymphocytes,
      differentiated into Th1 gamma interferon-producing cells, with a frequency that
      was up to 66-fold lower than that obtained for HAd5. We also compared CAV-2 to
      prototype HAd from five of the six human species and found that CAV-2-induced
      cellular proliferation was similar to that found with rare HAd serotypes.
      Individual CAV-2 capsid proteins also induced less proliferation than their HAd5
      homologues. Our data suggest that CAV-2 vectors may be safer (i.e., less
      immunogenic) for gene transfer but are not without a theoretical risk in a subset
      of potential patients.

PMID- 16282460
TI  - Protective and therapeutic capacity of human single-chain Fv-Fc fusion proteins
      against West Nile virus.
AB  - West Nile virus has spread rapidly across the United States, and there is
      currently no approved human vaccine or therapy to prevent or treat disease.
      Passive immunization with antibodies against the envelope protein represents a
      promising means to provide short-term prophylaxis and treatment for West Nile
      virus infection. In this study, we identified a panel of 11 unique human single
      chain variable region antibody fragments (scFvs) that bind the envelope protein
      of West Nile virus. Selected scFvs were converted to Fc fusion proteins (scFv
      Fcs) and were tested in mice for their ability to prevent lethal West Nile virus
      infection. Five of these scFv-Fcs, 11, 15, 71, 85, and 95, protected 100% of mice
      from death when given prior to infection with virus. Two of them, 11 and 15,
      protected 80% of mice when given at days 1 and 4 after infection. In addition,
      four of the scFv-Fcs cross-neutralized dengue virus, serotype 2. Binding assays
      using yeast surface display demonstrated that all of our scFvs bind to sites
      within domains I and II of West Nile virus envelope protein. These recombinant
      human scFvs are potential candidates for immunoprophylaxis and therapy of
      flavivirus infections.

PMID- 16282462
TI  - Neutrophils interact with adenovirus vectors via Fc receptors and complement
      receptor 1.
AB  - Neutrophils are effectors of the innate immune response to adenovirus vectors.
      Following the systemic administration of Cy2-labeled AdLuc in mice, flow
      cytometry and PCR analysis of liver leukocytes revealed that 25% of recruited
      neutrophils interacted with adenovirus vectors. In vitro, flow cytometry of human
      neutrophils incubated with Cy2-labeled AdLuc also demonstrated a significant
      interaction with adenovirus vectors. Fluorescence and electron microscopy
      confirmed vector internalization by neutrophils. The AdLuc-neutrophil interaction
      reduced vector transduction efficiency by more than 50% in coincubation assays in
      epithelium-derived cells. Adenovirus vector uptake by neutrophils occurred
      independently of coxsackievirus adenovirus receptor (CAR) and capsid RGD motifs,
      since neutrophils do not express CAR and uptake of the RGD-deleted vector AdL.PB*
      was similar to that of AdLuc. Furthermore, both AdLuc and AdL.PB* activated
      neutrophils and induced similar degrees of L-selectin shedding. Neutrophil uptake
      of AdLuc was dependent on the presence of complement and antibodies, since the
      interaction between AdLuc and neutrophils was significantly reduced when they
      were incubated in immunoglobulin G-depleted or heat-inactivated human serum.
      Blocking of complement receptor 1 (CD35) but not complement receptor 3
      (CD11b/CD18) significantly reduced neutrophil uptake of AdLuc. Blocking of Fc
      gammaRI (CD64), Fc gammaRII (CD32), and Fc gammaRIII (CD16) individually or
      together also reduced neutrophil uptake of AdLuc, although less than blocking of
      CD35 alone. Combined CR1 and Fc receptor blockade synergistically inhibited
      neutrophil-AdLuc interactions close to baseline. These results demonstrate
      opsonin-dependent adenovirus vector interactions with neutrophils and their
      corresponding receptors.

PMID- 16282461
TI  - ACE2 receptor expression and severe acute respiratory syndrome coronavirus
      infection depend on differentiation of human airway epithelia.
AB  - Studies of patients with severe acute respiratory syndrome (SARS) demonstrate
      that the respiratory tract is a major site of SARS-coronavirus (CoV) infection
      and disease morbidity. We studied host-pathogen interactions using native lung
      tissue and a model of well-differentiated cultures of primary human airway
      epithelia. Angiotensin converting enzyme 2 (ACE2), the receptor for both the SARS
      CoV and the related human respiratory coronavirus NL63, was expressed in human
      airway epithelia as well as lung parenchyma. As assessed by immunofluorescence
      staining and membrane biotinylation, ACE2 protein was more abundantly expressed
      on the apical than the basolateral surface of polarized airway epithelia.
      Interestingly, ACE2 expression positively correlated with the differentiation
      state of epithelia. Undifferentiated cells expressing little ACE2 were poorly
      infected with SARS-CoV, while well-differentiated cells expressing more ACE2 were
      readily infected. Expression of ACE2 in poorly differentiated epithelia
      facilitated SARS spike (S) protein-pseudotyped virus entry. Consistent with the
      expression pattern of ACE2, the entry of SARS-CoV or a lentivirus pseudotyped
      with SARS-CoV S protein in differentiated epithelia was more efficient when
      applied to the apical surface. Furthermore, SARS-CoV replicated in polarized
      epithelia and preferentially exited via the apical surface. The results indicate
      that infection of human airway epithelia by SARS coronavirus correlates with the
      state of cell differentiation and ACE2 expression and localization. These
      findings have implications for understanding disease pathogenesis associated with
      SARS-CoV and NL63 infections.

PMID- 16282463
TI  - The cotton rat provides a novel model to study genital herpes infection and to
      evaluate preventive strategies.
AB  - Prevention of genital herpes and other sexually transmitted infections (STI) is a
      critical health priority because of the overwhelming impact on women and infants
      and the epidemiological association with human immunodeficiency virus (HIV)/AIDS.
      Small animal models are essential for evaluating strategies for prevention or
      treatment of STI. Neither the murine nor the guinea pig model of genital herpes
      fully recapitulates human disease. We demonstrate that herpes simplex virus type
      2 (HSV-2) readily infects inbred cotton rats (Sigmodon hispidus). Consistent
      infection does not require pretreatment with medroxyprogesterone, and primary
      disease resembles that observed in humans. The animals develop genital lesions
      and fully recover. During primary infection, viral DNA is also detected in liver,
      lungs, brain, and kidneys. Clinical self-limited recurrences occur spontaneously
      but may also be induced by dexamethasone. Pretreatment of cotton rats with PRO
      2000 gel, a candidate vaginal microbicide being evaluated in clinical trials to
      prevent HSV and HIV, protects cotton rats from HSV. Together, these studies
      suggest that the cotton rat may provide an excellent model to study genital
      herpes and to evaluate preventive strategies.

PMID- 16282464
TI  - Central nervous system pathology caused by autoreactive CD8+ T-cell clones
      following virus infection.
AB  - Theiler's murine encephalomyelitis virus (TMEV) causes a demyelinating disease in
      infected mice which has similarities to multiple sclerosis. Spleen cells from
      TMEV-infected SJL/J mice stimulated with antigen-presenting cells infected with
      TMEV resulted in a population of autoreactive CD8+ cytotoxic T cells that kill
      uninfected syngeneic cells. We established CD8+ T cell clones that could kill
      both TMEV-infected and uninfected syngeneic targets, although infected target
      cells were killed more efficiently. The CD8+ T-cell clones produced gamma
      interferon when incubated with either infected or uninfected syngeneic target
      cells. Intracerebral injection of the clones into naive mice induced
      degeneration, not only in the brain, but also in the spinal cord. This suggests
      that CD8+ Tc1 cells could play a pathogenic role in central nervous system
      inflammation.

PMID- 16282465
TI  - Functional divergence of Kaposi's sarcoma-associated herpesvirus and related
      gamma-2 herpesvirus thymidine kinases: novel cytoplasmic phosphoproteins that
      alter cellular morphology and disrupt adhesion.
AB  - The nucleoside kinase encoded by Kaposi's sarcoma-associated herpesvirus (KSHV)
      is a relatively inefficient enzyme with substrate specificity for thymidine
      alone, unlike alphaherpesvirus thymidine kinases (TKs). Similar to all
      gammaherpesvirus TKs, KSHV TK is composed of two distinct domains, a conserved C
      terminal kinase and a novel and uncharacterized N terminus. Ectopic expression of
      KSHV TK in adherent cells induced striking morphological changes and anchorage
      independence although cells survived, a property shared with the related
      rhadinovirus TKs of rhesus monkey rhadinovirus and herpesvirus saimiri. To
      determine whether KSHV TK served alternate functions relevant to the rhadinovirus
      life cycle and to reveal the contribution of the N terminus, an enhanced green
      fluorescent protein-tagged fusion protein and serial mutants were generated for
      investigation of intracellular localization and cell biology. Analysis of
      truncation mutants showed that a proline-rich region located within the N
      terminus cooperated with the conserved C-terminal kinase to tether KSHV TK to a
      reticular network in the cytoplasm and to induce morphological change. Fusion of
      the KSHV N terminus to herpes simplex virus type 1 TK, a nucleus-localized
      enzyme, similarly resulted in cytoplasmic redistribution of the chimeric protein
      but did not alter cell shape or adhesion. Unlike other human herpesvirus TKs,
      KSHV TKs and related rhadinovirus TKs are constitutively tyrosine phosphorylated;
      a KSHV TK mutant that was hypophosphorylated failed to detach and grow in
      suspension. Loss of adhesion may enhance terminal differentiation, viral
      replication, and egress at the cellular level and at the organism level may
      facilitate detachment and distant migration of KSHV-replicating cells within body
      fluids--promoting oropharyngeal transmission and perhaps contributing to the
      multifocal lesions that characterize KS.

PMID- 16282466
TI  - Interaction of the putative human cytomegalovirus portal protein pUL104 with the
      large terminase subunit pUL56 and its inhibition by benzimidazole-D
      ribonucleosides.
AB  - Herpesvirus DNA replication leads to unit length genomes that are translocated
      into preformed procapsids through a unique portal vertex. The translocation is
      performed by the terminase that cleaves the DNA and powers the insertion by its
      ATPase activity. Recently, we demonstrated that the putative human
      cytomegalovirus (HCMV) portal protein, pUL104, also forms high-molecular-weight
      complexes. Analyses now have been performed to determine the intracellular
      localization and identification of interaction partners of pUL104. In infected
      cells, HCMV pUL104 was found to be predominantly localized throughout the nucleus
      as well as in cytoplasmic clusters at late times of infection. The latter
      localization was abolished by phosphonoacetic acid, an inhibitor of viral DNA
      replication. Immunofluorescence revealed that pUL104 colocalized with pUL56, the
      large subunit of the HCMV terminase. Specific association of in vitro translated
      pUL104 with the carboxy-terminal half of GST-UL56C was detected. By using
      coimmunoprecipitations a direct interaction with pUL56 was confirmed. In
      addition, this interaction was no longer detected when the benzimidazole-D
      nucleosides BDCRB or Cl4RB were added, thus indicating that these HCMV inhibitors
      block the insertion of the DNA into the capsid by preventing a necessary
      interaction of pUL56 with the portal. Electron microscopy revealed that in the
      presence of Cl4RB DNA is not packaged into capsids and these capsids failed to
      egress from the nucleus. Furthermore, pulsed-field gel electrophoresis showed
      that DNA concatemers synthesized in the presence of the compound failed to be
      processed.

PMID- 16282468
TI  - Invasion and maintenance of dengue virus type 2 and type 4 in the Americas.
AB  - Dengue virus type 4 (DENV-4) was first reported in the Americas in 1981, where it
      caused epidemics of dengue fever throughout the region. In the same year, the
      region's first epidemic of dengue hemorrhagic fever was reported, caused by an
      Asian strain of dengue virus type 2 (DENV-2) that was distinct from the American
      subtype circulating previously. Despite the importance of these epidemics, little
      is known about the rates or determinants of viral spread among island and
      mainland populations or their directions of movement. We employed a Bayesian
      coalescent approach to investigate the transmission histories of DENV-2 and DENV
      4 since their introduction in 1981 and a parsimony method to assess patterns of
      strain migration. For both viruses there was an initial invasion phase
      characterized by an exponential increase in the number of DENV lineages, after
      which levels of genetic diversity remained constant despite reported fluctuations
      in DENV-2 and DENV-4 activity. Strikingly, viral lineage numbers increased far
      more rapidly for DENV-4 than DENV-2, indicative of a more rapid rate of
      exponential population growth in DENV-4 or a higher rate of geographic dispersal,
      allowing this virus to move more effectively among localities. We propose that
      these contrasting dynamics may reflect underlying differences in patterns of host
      immunity. Despite continued gene flow along particular transmission routes, the
      overall extent of viral traffic was less than expected under panmixis. Hence,
      DENV in the Americas has a clear geographic structure that maintains viral
      diversity between outbreaks.

PMID- 16282467
TI  - Murine gammaherpesvirus 68 infection is associated with lymphoproliferative
      disease and lymphoma in BALB beta2 microglobulin-deficient mice.
AB  - Human gammaherpesvirus infections are associated with development of
      lymphoproliferative disease. Understanding of the mechanisms of gammaherpesvirus
      lymphomagenesis during chronic infection in a natural host has been limited by
      the exquisite species specificity of human gammaherpesviruses and the expense of
      primates. Murine gammaherpesvirus gammaHV68 is genetically and biologically
      related to human gammaherpesviruses and herpesvirus saimiri and has been reported
      to be associated with lymphoproliferative disease in mice (N. P. Sunil-Chandra,
      J. Arno, J. Fazakerley, and A. A. Nash, Am. J. Pathol. 145:818-826, 1994). We
      report the development of an animal model of gammaHV68 lymphomagenesis in BALB/c
      beta2 microglobulin-deficient mice (BALB beta2m-/-). GammaHV68 infection induced
      two lymphoproliferative lesions: B-cell lymphoma and atypical lymphoid
      hyperplasia (ALH). ALH lesion histology resembled lesions of Epstein-Barr virus
      associated posttransplant lymphoproliferative disease and was characterized by
      the abnormal infiltration of the white pulp with cells expressing the plasma cell
      marker CD138. Lymphomas observed in gammaHV68-infected animals were B220+/CD3-
      large-cell lymphomas. GammaHV68-infected cells were common in ALH lesions as
      measured by in situ hybridization with a probe specific for viral tRNAs (vtRNAs),
      but they were scarce in gammaHV68-infected spleens with normal histology. Unlike
      ALH lesions, gammaHV68 vtRNA-positive cells were rare in lymphomas. GammaHV68
      infection of BALB beta2m-/- mice results in lymphoproliferation and lymphoma,
      providing a valuable tool for identifying viral and host genes involved in
      gammaherpesvirus-associated malignancies. Our findings suggest that gammaHV68
      induces lymphomas via hit-and-run oncogenesis, paracrine effects, or stimulation
      of chronic inflammation.

PMID- 16282469
TI  - Antigen expression kinetics and immune responses of mice immunized with
      noninfectious simian-human immunodeficiency virus DNA.
AB  - In a previous report we demonstrated that three injections of an rt-deleted
      noninfectious genome of the simian-human immunodeficiency virus SHIV(KU2) induced
      protection against AIDS in macaques (D. K. Singh, Z. Liu, D. Sheffer, G. A.
      Mackay, M. Smith, S. Dhillon, R. Hegde, F. Jia, I. Adany, and O. Narayan, J.
      Virol 79:3419-3428, 2005). To make this DNA safer, we deleted two more genes, the
      integrase gene and vif, along with the 3' long terminal repeat. We also replaced
      the gag, pro, and nef genes (SIVmac239 origin) with those of human
      immunodeficiency virus (HIV) type 1 strain SF2. The resultant construct,
      designated delta4SHIV(KU2) DNA, was used in this study to evaluate gene
      expression and immunogenicity in BALB/c mice. DNA-transfected human embryonic
      kidney epithelial cells (HEK 293) produced all of the major viral proteins and
      released p24 in the supernatant for 12 days. Inoculation of the vaccine DNA into
      the gastrocnemius muscles resulted in intense mononuclear cell infiltration at
      the inoculated sites and the production of viral p24 in myocytes, in infiltrating
      mononuclear cells, and in cells in the spleen and draining lymph nodes between 3
      and 10 days postinoculation. Expression of p24 in the muscle cells peaked at day
      7 and became undetectable after day 12. The same 12-day period of expression of
      p24 was observed in mice that were given a second injection 4 weeks after the
      first. Evaluation of immune responses in BALB/c mice revealed that the DNA
      induced enzyme-linked immunospot and antigen-specific proliferative cell-mediated
      immunity responses. The responses were stronger in mice that were coinjected with
      a second plasmid expressing granulocyte-macrophage colony-stimulating factor.
      Since new waves of viral antigen production could be induced with each boosting
      injection of the vaccine DNA, this DNA could be a safe and efficient agent to
      induce long-term protection against HIV.

PMID- 16282470
TI  - MysTR: an endogenous retrovirus family in mammals that is undergoing recent
      amplifications to unprecedented copy numbers.
AB  - A large percentage of the repetitive elements in mammalian genomes are
      retroelements, which have been moved primarily by LINE-1 retrotransposons and
      endogenous retroviruses. Although LINE-1 elements have remained active throughout
      the mammalian radiation, specific groups of endogenous retroviruses generally
      remain active for comparatively shorter periods of time. Identification of an
      unusual extinction of LINE-1 activity in a group of South American rodents has
      opened a window for examination of the interplay in mammalian genomes between
      these ubiquitous retroelements. In the course of a search for any type of
      repetitive sequences whose copy numbers have substantially changed in Oryzomys
      palustris, a species that has lost LINE-1 activity, versus Sigmodon hispidus, a
      closely related species retaining LINE-1 activity, we have identified an
      endogenous retrovirus family differentially amplified in these two species.
      Analysis of three full-length, recently transposed copies, called mysTR elements,
      revealed gag, pro, and pol coding regions containing stop codons which may have
      accumulated either before or after retrotransposition. Isolation of related
      sequences in S. hispidus and the LINE-1 active outgroup species, Peromyscus
      maniculatus, by PCR of a pro-pol region has allowed determination of copy numbers
      in each species. Unusually high copy numbers of approximately 10,000 in O.
      palustris versus 1,000 in S. hispidus and 4,500 in the more distantly related P.
      maniculatus leave open the question of whether there is a connection between
      endogenous retrovirus activity and LINE-1 inactivity. Nevertheless, these
      independent expansions of mysTR represent recent amplifications of this
      endogenous retrovirus family to unprecedented levels.

PMID- 16282471
TI  - The neuronal host cell factor-binding protein Zhangfei inhibits herpes simplex
      virus replication.
AB  - During lytic infection in epithelial cells the expression of herpes simplex virus
      type 1 (HSV-1) immediate-early (IE) genes is initiated by a multiprotein complex
      comprising the virion-associated protein VP16 and two cellular proteins, host
      cellular factor (HCF) and Oct-1. Oct-1 directly recognizes TAATGARAT elements in
      promoters of IE genes. The role of HCF is not clear. HSV-1 also infects sensory
      neurons innervating the site of productive infection and establishes a latent
      infection in these cells. It is likely that some VP16 is retained by the HSV-1
      nucleocapsid as it reaches the neuronal nucleus. Its activity must therefore be
      suppressed for successful establishment of viral latency. Recently, we discovered
      an HCF-binding cellular protein called Zhangfei. Zhangfei, in an HCF-dependent
      manner, inhibits Luman/LZIP/CREB3, another cellular HCF-binding transcription
      factor. Here we show that Zhangfei is selectively expressed in human neurons.
      When delivered to cultured cells that do not normally express the protein,
      Zhangfei inhibited the ability of VP16 to activate HSV-1 IE expression. The
      inhibition was specific for HCF-dependent transcriptional activation by VP16,
      since a Gal4-VP16 chimeric protein was inhibited only on a TAATGARAT-containing
      promoter and not a on a Gal4-containing promoter. Zhangfei associated with VP16
      and inhibited formation of the VP16-HCF-Oct-1 complex on TAATGARAT motifs.
      Zhangfei also suppressed HSV-1-induced expression of several cellular genes
      including topoisomerase IIalpha, suggesting that in addition to suppressing IE
      expression Zhangfei may have an inhibitory effect on HSV-1 DNA replication and
      late gene expression.

PMID- 16282472
TI  - The conserved poxvirus L3 virion protein is required for transcription of
      vaccinia virus early genes.
AB  - We provide the initial characterization of the product of the vaccinia virus L3L
      open reading frame (VACWR090), which is conserved in all sequenced members of the
      poxvirus family. The predicted polypeptide contains no motifs or other features
      that provided a clue to the role of the L3 protein, and no functional information
      was available regarding a homolog discovered in Plasmodium falciparum. The L3
      protein was expressed following viral DNA replication, a finding consistent with
      a putative late promoter sequence, and was packaged as a non-membrane protein in
      mature virus particles. A recombinant virus, in which the L3L gene was regulated
      by the Escherichia coli lac operator/repressor system, had a conditional lethal
      phenotype. The virus replicated in the presence of inducer, but in its absence,
      the yields of infectious virus were reduced by 99%. When cells were infected
      without inducer, however, no defect in gene expression or morphogenesis was
      noted. Virus particles lacking L3, which assembled in the absence of inducer,
      were indistinguishable from wild-type virions with regard to morphology, major
      structural proteins, and DNA content but were noninfectious. L3-deficient virions
      were able to bind and penetrate cells but produced extremely small amounts of
      viral early mRNA. A defect in transcription was demonstrated by in vitro studies
      with permeabilized virions, but soluble extracts of L3-deficient virions showed
      normal levels of template-dependent transcriptional activity, indicating that
      only transcription of the packaged genome is impaired.

PMID- 16282473
TI  - A mutation in the first ligand-binding repeat of the human very-low-density
      lipoprotein receptor results in high-affinity binding of the single V1 module to
      human rhinovirus 2.
AB  - Minor group human rhinoviruses (HRVs) bind members of the low-density lipoprotein
      receptor family for cell entry. The ligand-binding domains of these membrane
      proteins are composed of various numbers of direct repeats of about 40 amino
      acids in length. Residues involved in binding of module 3 (V3) of the very-low
      density lipoprotein receptor (VLDLR) to HRV2 have been identified by X-ray
      crystallography (N. Verdaguer, I. Fita, M. Reithmayer, R. Moser, and D. Blaas,
      Nat. Struct. Mol. Biol. 11:429-434, 2004). Sequence comparisons of the eight
      repeats of VLDLR with respect to the residues implicated in the interaction
      between V3 and HRV2 suggested that (in addition to V3) V1, V2, V5, and V6 also
      fulfill the requirements for interacting with the virus. Using a highly sensitive
      binding assay employing phage display, we demonstrate that single modules V2, V3,
      and V5 indeed bind HRV2. However, V1 does not. A single mutation from threonine
      17 to proline converted the nonbinding wild-type form of V1 into a very strong
      binder. We interpret the dramatic increase in affinity by the generation of a
      hydrophobic patch between virus and receptor; in the presence of threonine, the
      contact area might be disturbed. This demonstrates that the interaction between
      virus and its natural receptors can be strongly enhanced by mutation.

PMID- 16282474
TI  - Mouse mammary tumor virus encodes a self-regulatory RNA export protein and is a
      complex retrovirus.
AB  - Mouse mammary tumor virus (MMTV) has been classified as a simple retrovirus with
      two accessory genes, dut and sag. Cloned MMTV proviruses carrying a trimethoprim
      (trim) cassette in the envelope gene were defective for Gag protein production
      and the nuclear export of unspliced gag-pol RNA. Complementation experiments
      indicated that a trans-acting product was responsible for the Gag defect of such
      mutants. Analysis of MMTV-infected cells revealed the presence of a novel, doubly
      spliced RNA that encodes a putative product of 301 amino acids. Overexpression of
      cDNA from this RNA increased Gag levels from env mutant proviruses or reporter
      gene expression from unspliced mRNAs and allowed detection of a 33-kDa protein
      product, which has been named regulator of export of MMTV mRNA, or Rem. The Rem N
      terminus has motifs similar to the Rev-like export proteins of complex
      retroviruses, and mutation of the nuclear localization signal (NLS) abolished RNA
      export and detection within the nucleus. The Rem C terminus has few identifiable
      features, but removal of this domain increased Rem-mediated export, suggesting an
      autoregulatory function. A reporter vector developed from the 3' end of the MMTV
      provirus was Rem responsive and required both the presence of the MMTV env-U3
      junction and a functional Crm1 pathway. The identification of a third accessory
      protein from a doubly spliced transcript suggests that MMTV is the first murine
      complex retrovirus to be documented. Manipulation of the MMTV genome may provide
      mouse models for human retroviral diseases, such as AIDS.

PMID- 16282475
TI  - Single-molecule analysis of human immunodeficiency virus type 1 gp120-receptor
      interactions in living cells.
AB  - A quantitative description of the binding interactions between human
      immunodeficiency virus (HIV) type 1 envelope glycoproteins and their host cell
      surface receptors remains incomplete. Here, we introduce a single-molecule
      analysis that directly probes the binding interactions between an individual
      viral subunit gp120 and a single receptor CD4 and/or chemokine coreceptor CCR5 in
      living cells. This analysis differentiates single-molecule binding from
      multimolecule avidity and shows that, while the presence of CD4 is required for
      gp120 binding to CCR5, the force required to rupture a single gp120-coreceptor
      bond is significantly higher and its lifetime is much longer than those of a
      single gp120-receptor bond. The lifetimes of these bonds are themselves shorter
      than those of the P-selectin/PSGL-1 bond involved in leukocyte attachment to the
      endothelium bonds during an inflammation response. These results suggest an
      amended model of HIV entry in which, immediately after the association of gp120
      to its receptor, gp120 seeks its coreceptor to rapidly form a new bond. This
      "bond transfer" occurs only if CCR5 is in close proximity to CD4 and CD4 is still
      attached to gp120. The analysis presented here may serve as a general framework
      to study mechanisms of receptor-mediated interactions between viral envelope
      proteins and host cell receptors at the single-molecule level in living cells.

PMID- 16282477
TI  - Interactions with pocket proteins contribute to the role of human papillomavirus
      type 16 E7 in the papillomavirus life cycle.
AB  - Human papillomaviruses (HPVs), most commonly the HPV16 genotype, are the
      principle etiological determinant for cervical cancer, a common cancer worldwide
      resulting in over 200,000 deaths annually. The oncogenic properties of HPVs are
      attributable in part to the virally encoded protein E7, best known for its
      ability to bind to and induce the degradation of the retinoblastoma tumor
      suppressor, pRb, and related "pocket proteins" p107 and p130. Previously, we
      defined a role for E7 in the productive stage of the HPV16 life cycle, which
      takes place in stratified squamous epithelia. HPV perturbs the normal processes
      of cell growth and differentiation of stratified squamous epithelia. HPVs
      reprogram cells to support continued DNA synthesis and inhibit their
      differentiation in the suprabasal compartment of the epithelia, where cells
      normally have withdrawn from the cell cycle and initiated a well-defined pattern
      of terminal differentiation. These virus-induced perturbations, which contribute
      to the production of progeny HPVs, are dependent on E7. In this study, we define
      the mechanism of action by which E7 contributes to the productive stage of the
      HPV16 life cycle. We found that the ability of HPV16 to reprogram suprabasal
      cells to support DNA synthesis correlates with E7's ability to bind pocket
      proteins but not its ability to induce their degradation. In contrast, the
      ability of HPV16 to perturb differentiation correlated with both E7's binding to
      and degradation of pocket proteins. These data indicate that different hallmarks
      of the productive stage of the HPV16 life cycle rely upon different sets of
      requirements for E7.

PMID- 16282476
TI  - Human parainfluenza virus type 4 is incapable of evading the interferon-induced
      antiviral effect.
AB  - The V proteins of some paramyxoviruses have developed the ability to efficiently
      inactivate STAT protein function as a countermeasure for evading interferon (IFN)
      responses. Human parainfluenza virus type 4 (hPIV4) is one of the rubulaviruses,
      which are members of the family Paramyxoviridae, and has a V protein with a
      highly conserved cysteine-rich domain that is the hallmark of paramyxovirus V
      proteins. In order to study the function of the hPIV4 V protein, we established
      HeLa cells expressing the hPIV4A V protein (HeLa/FlagPIV4V). The hPIV4 V protein
      had no ability to reduce the level of STAT1 or STAT2, although it associated with
      STAT1, STAT2, DDB1, and Cul4A. It interfered with neither STAT1 and STAT2
      tyrosine phosphorylation nor IFN-induced STAT nuclear accumulation. In addition,
      HeLa/FlagPIV4V cells are fully sensitive to both beta interferon (IFN-beta) and
      IFN-gamma, indicating that the hPIV4 V protein has no ability to block IFN
      induced signaling. We further established HeLa cells expressing various chimeric
      proteins between the hPIV2 and hPIV4A V proteins. The lack of IFN-antagonistic
      activity of the hPIV4 V protein is caused by both the P/V common and V-specific
      domains. At least two regions (amino acids [aa] 32 to 45 and aa 143 to 164) of
      hPIV4 V in the P/V common domain and one region (aa 200 to 212) of the C terminus
      are involved in the inability to evade the IFN-induced signaling. Moreover, we
      established HeLa cells persistently infected with hPIV4 to make sure of the
      inability to escape IFN and confirmed that hPIV4 is the only paramyxovirus
      analyzed to date that can't evade the IFN-induced antiviral responses.

PMID- 16282478
TI  - Molecular characterization of adeno-associated viruses infecting children.
AB  - Although adeno-associated virus (AAV) infection is common in humans, the biology
      of natural infection is poorly understood. Since it is likely that many primary
      AAV infections occur during childhood, we set out to characterize the frequency
      and complexity of circulating AAV isolates in fresh and archived frozen human
      pediatric tissues. Total cellular DNA was isolated from 175 tissue samples
      including freshly collected tonsils (n = 101) and archived frozen samples
      representing spleen (n = 21), lung (n = 16), muscle (n = 15), liver (n = 19), and
      heart (n = 3). Samples were screened for the presence of AAV and adenovirus
      sequences by PCR using degenerate primers. AAV DNA was detected in 7 of 101 (7%)
      tonsil samples and two of 74 other tissues (one spleen and one lung). Adenovirus
      sequences were identified in 19 of 101 tonsils (19%), but not in any other
      tissues. Complete capsid gene sequences were recovered from all nine AAV-positive
      tissues. Sequence analyses showed that eight of the capsid sequences were AAV2
      like (approximately 98% amino acid identity), while the single spleen isolate was
      intermediate between serotypes 2 and 3. Comparison to the available AAV2 crystal
      structure revealed that the majority of the amino acid substitutions mapped to
      surface-exposed hypervariable domains. To further characterize the AAV capsid
      structure in these samples, we used a novel linear rolling-circle amplification
      method to amplify episomal AAV DNA and isolate infectious molecular clones from
      several human tissues. Serotype 2-like viruses were generated from these DNA
      clones and interestingly, failed to bind to a heparin sulfate column. Inspection
      of the capsid sequence from these two clones (and the other six AAV2-like
      isolates) revealed that they lacked arginine residues at positions 585 and 588 of
      the capsid protein, which are thought to be essential for interaction with the
      heparin sulfate proteoglycan coreceptor. These data provide a framework with
      which to explore wild-type AAV persistence in vivo and provide additional tools
      to further define the biodistribution and form of AAV in human tissues.

PMID- 16282479
TI  - Characterization of adeno-associated virus genomes isolated from human tissues.
AB  - Infection with wild-type adeno-associated virus (AAV) is common in humans, but
      very little is known about the in vivo biology of AAV. On a molecular level, it
      has been shown in cultured cells that AAV integrates in a site-specific manner on
      human chromosome 19, but this has never been demonstrated directly in infected
      human tissues. To that end, we tested 175 tissue samples for the presence of AAV
      DNA, and when present, examined the specific form of the viral DNA. AAV was
      detected in 7 of 101 tonsil-adenoid samples and in 2 of 74 other tissue samples
      (spleen and lung). In these nine samples, we were unable to detect AAV
      integration in the AAVS1 locus using a sensitive PCR assay designed to amplify
      specific viral-cellular DNA junctions. Additionally, we used a second
      complementary assay, linear amplification-mediated-PCR (LAM-PCR) to widen our
      search for integration events. Analysis of individual LAM-PCR products revealed
      that the AAV genomes were arranged predominantly in a head-to-tail array, with
      deletions and extensive rearrangements in the inverted terminal repeat sequences.
      A single AAV-cellular junction was identified from a tonsil sample and it mapped
      to a highly repetitive satellite DNA element on chromosome 1. Given these data,
      we entertained the possibility that instead of integrated forms, AAV genomes were
      present as extrachromosomal forms. We used a novel amplification assay (linear
      rolling-circle amplification) to show that the majority of wild-type AAV DNA
      existed as circular double-stranded episomes in our tissues. Thus, following
      naturally acquired infection, AAV DNA can persist mainly as circular episomes in
      human tissues. These findings are consistent with the circular episomal forms of
      recombinant AAV vectors that have been isolated and characterized from in vivo
      transduced tissues.

PMID- 16282480
TI  - Induction of neutralizing antibodies against human immunodeficiency virus type 1
      primary isolates by Gag-Env pseudovirion immunization.
AB  - A major challenge for the development of an effective HIV vaccine is to elicit
      neutralizing antibodies against a broad array of primary isolates. Monomeric
      gp120-based vaccine approaches have not been successful in inducing this type of
      response, prompting a number of approaches designed to recreate the native
      glycoprotein complex that exists on the viral membrane. Gag-Env pseudovirions are
      noninfectious viruslike particles that recreate the native envelope glycoprotein
      structure and have the potential to generate neutralizing antibody responses
      against primary isolates. In this study, an inducible cell line was created in
      order to generate Gag-Env pseudovirions for examination of neutralizing antibody
      responses in guinea pigs. Unadjuvanted pseudovirions generated relatively weak
      anti-gp120 responses, while the use of a block copolymer water-in-oil emulsion or
      aluminum hydroxide combined with CpG oligodeoxynucleotides resulted in high
      levels of antibodies that bind to gp120. Sera from immunized animals neutralized
      a panel of human immunodeficiency virus (HIV) type 1 primary isolate viruses at
      titers that were significantly higher than that of the corresponding monomeric
      gp120 protein. Interpretation of these results was complicated by the occurrence
      of neutralizing antibodies directed against cellular (non-envelope protein)
      components of the pseudovirion. However, a major component of the pseudovirion
      elicited antibody response was directed specifically against the HIV envelope.
      These results provide support for the role of pseudovirion-based vaccines in
      generating neutralizing antibodies against primary isolates of HIV and highlight
      the potential confounding role of antibodies directed at non-envelope cell
      surface components.

PMID- 16282481
TI  - Effect of cell cycle arrest on the activity of nucleoside analogues against human
      immunodeficiency virus type 1.
AB  - Human immunodeficiency virus (HIV) reverse transcription can be notably affected
      by cellular activation, differentiation, and division. We hypothesized that
      changes in the cell cycle could also affect HIV susceptibility to nucleoside
      analogues, which compete with natural nucleotides for incorporation into viral
      DNA and inhibit viral replication through premature termination of reverse
      transcription. Proliferating HeLa-derived indicator cells were arrested in the
      S/G2 phase with etoposide, a topoisomerase II inhibitor, or in the G1/S phase
      with aphidicolin, a polymerase alpha inhibitor. Cell cycle arrest by both agents
      induced a remarkable decrease in HIV susceptibility to zidovudine (AZT). This
      decrease was seen both with a single-cycle infectivity assay and with a viral DNA
      quantitation assay, indicating that the effect of cell cycle arrest was exerted
      at the reverse transcription stage. The increase in the 50% inhibitory
      concentration (IC50) seen with arrested cells was strongest for AZT (23-fold) and
      stavudine (21-fold) but more modest for other drugs (lamivudine, 11-fold;
      dideoxyinosine, 7-fold; and nevirapine, 3-fold). In drug-resistant reverse
      transcriptase mutants, the increase in AZT IC50 (relative to that in dividing
      cells) was most prominent with a Q151M mutant and was comparable to the wild type
      in other drug-resistant mutants. Quantitation of intracellular pools of dTTP and
      AZT 5'-triphosphate (AZTTP) showed that etoposide treatment induced a significant
      increase in intracellular dTTP and consequently a decrease in AZTTP/dTTP ratios,
      suggesting that the decrease in viral susceptibility to AZT was caused by reduced
      incorporation of the analogue into nascent viral DNA. These results emphasize the
      importance of cellular proliferation and deoxynucleoside triphosphate metabolism
      in HIV susceptibility to nucleoside analogues and underscore the need to study
      the activities of drugs of this class with natural target cells under
      physiological conditions of activation and proliferation.

PMID- 16282482
TI  - Induction of human immunodeficiency virus type 1-specific T cells by a bluetongue
      virus tubule-vectored vaccine prime-recombinant modified virus Ankara boost
      regimen.
AB  - In the absence of strategies for reliable induction of antibodies broadly
      neutralizing human immunodeficiency virus type 1 (HIV-1), vaccine efforts have
      shifted toward the induction of cell-mediated immunity. Here we describe the
      construction and immunogenicity of novel T-cell vaccine NS1.HIVA, which delivers
      the HIV-1 clade A consensus-derived immunogen HIVA on the surface of tubular
      structures spontaneously formed by protein NS1 of bluetongue virus. We
      demonstrated that NS1 tubules can accommodate a protein as large as 527 amino
      acids without losing their self-assembly capability. When injected into BALB/c
      mice by several routes, chimeric NS1.HIVA tubules induced HIV-1-specific major
      histocompatibility complex class I-restricted T cells. These could be boosted by
      modified virus Ankara expressing the same immunogen and generate a memory capable
      of gamma interferon (IFN-gamma) production, proliferation, and lysis of
      sensitized target cells. Induced memory T cells readily produced IFN-gamma 230
      days postimmunization, and upon a surrogate virus challenge, NS1.HIVA vaccine
      alone decreased the vaccinia virus vv.HIVA load in ovaries by 2 orders of
      magnitude 280 days after immunization. Thus, because of its T-cell immunogenicity
      and antigenic simplicity, the NS1 delivery system could serve as a priming agent
      for heterologous prime-boost vaccination regimens. Its usefulness in primates,
      including humans, remains to be determined.

PMID- 16282483
TI  - A wild goose metapneumovirus containing a large attachment glycoprotein is
      avirulent but immunoprotective in domestic turkeys.
AB  - The genomic structure and composition of an avian metapneumovirus (aMPV) recently
      isolated from wild Canada geese (goose 15a/01) in the United States, together
      with its replication, virulence, and immunogenicity in domestic turkeys, were
      investigated. The sizes of seven of the eight genes, sequence identity, and
      genome organization of goose aMPV were similar to those of turkey aMPV subtype C
      (aMPV/C) strains, indicating that it belonged to the subtype. However, the goose
      virus contained the largest attachment (G) gene of any pneumovirus or
      metapneumovirus, with the predicted G protein of 585 amino acids (aa) more than
      twice the sizes of G proteins from other subtype C viruses and human
      metapneumovirus and more than 170 aa larger than the G proteins from the other
      aMPV subtypes (subtypes A, B, and D). The large G gene resulted from a 1,015
      nucleotide insertion at 18 nucleotides upstream of the termination signal of the
      turkey aMPV/C G gene. Three other aMPV isolates from Canada geese had similarly
      large G genes, whereas analysis of recent aMPV strains circulating in U.S.
      turkeys did not indicate the presence of the goose virus-like strain. In vitro,
      the goose virus replicated to levels (2 x 10(5) to 5 x 10(5) 50% tissue culture
      infective dose) comparable to those produced by turkey aMPV/C strains. More
      importantly, the virus replicated efficiently in the upper respiratory tract of
      domestic turkeys but with no clinical signs in either day-old or 2-week-old
      turkeys. The virus was also horizontally transmitted to naive birds, and turkey
      infections with goose 15a/01 induced production of aMPV-specific antibodies.
      Challenging day-old or 2-week-old turkeys vaccinated with live goose aMPV
      resulted in lower clinical scores in 33% of the birds, whereas the rest of the
      birds had no detectable clinical signs of the upper respiratory disease,
      suggesting that the mutant virus may be a safe and effective vaccine against aMPV
      infection outbreaks in commercial turkeys.

PMID- 16282484
TI  - Latent infection with herpes simplex virus is associated with ongoing CD8+ T-cell
      stimulation by parenchymal cells within sensory ganglia.
AB  - CD8+ T-cell persistence can be seen in ganglia harboring latent herpes simplex
      virus (HSV) infection. While there is some evidence that these cells suppress
      virus reactivation, this view remains controversial. Given that maintenance of
      latency by CD8+ T cells would necessitate ongoing exposure to antigen within this
      site, we sought evidence for such chronic stimulation. Initial experiments showed
      infiltration by activated but not naive CD8+ T cells into ganglia harboring
      latent HSV infection. While such infiltration was independent of T-cell
      specificity, once recruited, only virus-specific T cells expressed high levels of
      preformed granzyme B, a marker of ongoing activation. Moreover, bone marrow
      replacement chimeras showed that these elevated granzyme levels were totally
      dependent on presentation by parenchymal cells within the ganglia. Overall, this
      study argues that activated CD8+ T cells are nonspecifically recruited into
      latently infected ganglia, and in this site they are exposed to ongoing antigen
      stimulation, most likely by infected neuronal cells.

PMID- 16282486
TI  - Specific recognition and cleavage of the plus-strand primer by reverse
      transcriptase.
AB  - Reverse transcriptases (RTs) of retroviruses and long terminal repeat (LTR)
      retrotransposons possess DNA polymerase and RNase H activities. During reverse
      transcription these activities are necessary for the programmed sequence of
      events that include template switching and primer processing. Integrase then
      inserts the completed cDNA into the genome of the host cell. The RT of the LTR
      retrotransposon Tf1 was subjected to random mutagenesis, and the resulting
      transposons were screened with genetic assays to test which mutations reduced
      reverse transcription and which inhibited integration. We identified a cluster of
      mutations in the RNase H domain of RT that were surprising because they blocked
      integration without reducing cDNA levels. The results of immunoblots demonstrated
      that these mutations did not reduce levels of RT or integrase. DNA blots showed
      that the mutations did not lower the amounts of full-length cDNA. The sequences
      of the 3' ends of the cDNA revealed that mutations within the cluster in RNase H
      specifically reduced the removal of the polypurine tract (PPT) primer from the
      ends of the cDNA. These results indicate that primer removal is not a necessary
      component of reverse transcription. The residues mutated in Tf1 RNase H are
      conserved in human immunodeficiency virus type 1 and make direct contact with DNA
      opposite the PPT. Thus, our results identify a conserved element in RT that
      contacts the PPT and is specifically required for PPT removal.

PMID- 16282485
TI  - Decreased migration of Langerhans precursor-like cells in response to human
      keratinocytes expressing human papillomavirus type 16 E6/E7 is related to reduced
      macrophage inflammatory protein-3alpha production.
AB  - Infection with high-risk human papillomavirus (HPV) types, particularly types 16
      and 18, contributes to 90% of cervical cancer cases. HPV infects cutaneous or
      mucosal epithelium, tissue that is monitored for microbial infection or damage by
      Langerhans cells. In lesions produced by HPV type 16, there is a reduction in
      numbers of immune cells, especially Langerhans cells. Langerhans precursor cells
      selectively express CCR6, the receptor for macrophage inflammatory protein 3alpha
      (MIP-3alpha), and function as potent immune responders to inflamed epithelium and
      initiators of the innate immune response. It has been reported that E6 and E7 of
      high-risk HPVs interfere with immune mediators in order to suppress the
      recruitment of immune cells and antiviral activities of infected cells. Here we
      show that, following proinflammatory stimulus, HPV-16 E6 and E7 inhibit MIP
      3alpha transcription, resulting in suppression of the migration of immature
      Langerhans precursor-like cells. Interestingly, the E6 and E7 proteins from the
      low-risk HPV types also inhibited MIP-3alpha transcription. These results suggest
      that one mechanism by which HPV-infected cells suppress the immune response may
      be through the inhibition of a vital alert signal, thus contributing to the
      persistence of HPV infection.

PMID- 16282487
TI  - Homo-oligomerization of Marburgvirus VP35 is essential for its function in
      replication and transcription.
AB  - The nucleocapsid protein VP35 of Marburgvirus, a filovirus, acts as the cofactor
      of the viral polymerase and plays an essential role in transcription and
      replication of the viral RNA. VP35 forms complexes with the genome encapsidating
      protein NP and with the RNA-dependent RNA polymerase L. In addition, a trimeric
      complex had been detected in which VP35 bridges L and the nucleoprotein NP. It
      has been presumed that the trimeric complex represents the active polymerase
      bound to the nucleocapsid. Here we present evidence that a predicted coiled-coil
      domain between amino acids 70 and 120 of VP35 is essential and sufficient to
      mediate homo-oligomerization of the protein. Substitution of leucine residues 90
      and 104 abolished (i) the probability to form coiled coils, (ii) homo
      oligomerization, and (iii) the function of VP35 in viral RNA synthesis. Further,
      it was found that homo-oligomerization-negative mutants of VP35 could not bind to
      L. Thus, it is presumed that homo-oligomerization-negative mutants of VP35 are
      unable to recruit the polymerase to the NP/RNA template. In contrast, inability
      to homo-oligomerize did not abolish the recruitment of VP35 into inclusion
      bodies, which contain nucleocapsid-like structures formed by NP. Finally,
      transcriptionally inactive mutants of VP35 containing the functional homo
      oligomerization domain displayed a dominant-negative phenotype. Inhibition of
      VP35 oligomerization might therefore represent a suitable target for antiviral
      intervention.

PMID- 16282488
TI  - CD8+ and CD20+ lymphocytes cooperate to control acute simian immunodeficiency
      virus/human immunodeficiency virus chimeric virus infections in rhesus monkeys:
      modulation by major histocompatibility complex genotype.
AB  - We have previously described two isogenic molecularly cloned simian
      immunodeficiency virus/human immunodeficiency virus chimeric viruses (SHIVs) that
      differ from one another by 9 amino acids and direct distinct clinical outcomes in
      inoculated rhesus monkeys. SHIV(DH12R-Clone 7), like other highly pathogenic
      CXCR4-tropic SHIVs, induces rapid and complete depletions of CD4+ T lymphocytes
      and immunodeficiency in infected animals. In contrast, macaques inoculated with
      SHIV(DH12R-Clone 8) experience only partial and transient losses of CD4+ T cells,
      show prompt control of their viremia, and remain healthy for periods of time
      extending for up to 4 years. The contributions of CD8+ and CD20+ lymphocytes in
      suppressing the replication of the attenuated SHIV(DH12R-Clone 8) and maintaining
      a prolonged asymptomatic clinical course was assessed by treating animals with
      monoclonal antibodies that deplete each lymphocyte subset at the time of virus
      inoculation. The absence of either CD8+ or CD20+ cells during the SHIV(DH12R
      Clone 8) acute infection resulted in the rapid, complete, and irreversible loss
      of CD4+ T cells; sustained high levels of postpeak plasma viremia; and
      symptomatic disease in Mamu-A*01-negative Indian rhesus monkeys. In Mamu-A*01
      positive animals, however, the aggressive, highly pathogenic phenotype was
      observed only in macaques depleted of CD8+ cells; SHIV(DH12R-Clone 8) was
      effectively controlled in Mamu-A*01-positive monkeys in the absence of B
      lymphocytes. Taken together, these results indicate that both CD8+ and CD20+ B
      cells contribute to the control of primate lentiviral infection in Mamu-A*01
      negative macaques. Furthermore, the major histocompatibility complex genotype of
      an infected animal, as exemplified by the Mamu-A*01 allele in this study, has the
      additional capacity to shift the balance of the composite immune response.

PMID- 16282489
TI  - Skin hyperproliferation and susceptibility to chemical carcinogenesis in
      transgenic mice expressing E6 and E7 of human papillomavirus type 38.
AB  - The oncoproteins E6 and E7 of human papillomavirus type 38 (HPV38) display
      several transforming activities in vitro, including immortalization of primary
      human keratinocytes. To evaluate the oncogenic activities of the viral proteins
      in an in vivo model, we generated transgenic mice expressing HPV38 E6 and E7
      under the control of the bovine homologue of the human keratin 10 (K10) promoter.
      Two distinct lines of HPV38 E6/E7-expressing transgenic mice that express the
      viral genes at different levels were obtained. In both lines, HPV38 E6 and E7
      induced cellular proliferation, hyperplasia, and dysplasia in the epidermis. The
      rate of occurrence of these events was proportional to the levels of HPV38 E6 and
      E7 expression in the two transgenic lines. Exposure of the epidermis of
      nontransgenic mice to UV led to p21WAF1 accumulation and cell cycle arrest. In
      contrast, keratinocytes from transgenic mice continued to proliferate and were
      not positive for p21WAF1, indicating that cell cycle checkpoints are altered in
      keratinocytes expressing the viral genes. Although the HPV38 E6/E7-expressing
      transgenic mice did not develop spontaneous tumors during their life span, two
      stage carcinogen treatment led to a high incidence of papillomas,
      keratoacanthomas, and squamous-cell carcinomas in HPV38 mice compared with
      nontransgenic animals. Together, these data show that HPV38 E6 and E7 display
      transforming properties in vivo, providing further support for the role of HPV38
      in carcinogenesis.

PMID- 16282490
TI  - Severe acute respiratory syndrome coronavirus group-specific open reading frames
      encode nonessential functions for replication in cell cultures and mice.
AB  - SARS coronavirus (SARS-CoV) encodes several unique group-specific open reading
      frames (ORFs) relative to other known coronaviruses. To determine the
      significance of the SARS-CoV group-specific ORFs in virus replication in vitro
      and in mice, we systematically deleted five of the eight group-specific ORFs,
      ORF3a, OF3b, ORF6, ORF7a, and ORF7b, and characterized recombinant virus
      replication and gene expression in vitro. Deletion of the group-specific ORFs of
      SARS-CoV, either alone or in various combinations, did not dramatically influence
      replication efficiency in cell culture or in the levels of viral RNA synthesis.
      The greatest reduction in virus growth was noted following ORF3a deletion. SARS
      CoV spike (S) glycoprotein does not encode a rough endoplasmic reticulum
      (rER)/Golgi retention signal, and it has been suggested that ORF3a interacts with
      and targets S glycoprotein retention in the rER/Golgi apparatus. Deletion of
      ORF3a did not alter subcellular localization of the S glycoprotein from distinct
      punctuate localization in the rER/Golgi apparatus. These data suggest that ORF3a
      plays little role in the targeting of S localization in the rER/Golgi apparatus.
      In addition, insertion of the 29-bp deletion fusing ORF8a/b into the single ORF8,
      noted in early-stage SARS-CoV human and civet cat isolates, had little if any
      impact on in vitro growth or RNA synthesis. All recombinant viruses replicated to
      wild-type levels in the murine model, suggesting that either the group-specific
      ORFs play little role in in vivo replication efficiency or that the mouse model
      is not of sufficient quality for discerning the role of the group-specific ORFs
      in disease origin and development.

PMID- 16282491
TI  - Contribution of GADD45 family members to cell death suppression by cellular Bcl
      xL and cytomegalovirus vMIA.
AB  - Mammalian cells and viruses encode inhibitors of programmed cell death that
      localize to mitochondria and suppress apoptosis initiated by a wide variety of
      inducers. Mutagenesis was used to probe the role of a predicted alpha-helical
      region within the hydrophobic antiapoptotic domain (AAD) of cytomegalovirus vMIA,
      the UL37x1 gene product. This region was found to be essential for cell death
      suppression activity. A screen for proteins that interacted with the AAD of
      functional vMIA but that failed to interact with mutants identified growth arrest
      and DNA damage 45 (GADD45alpha), a cell cycle regulatory protein activated by
      genotoxic stress, as a candidate cellular binding partner. GADD45alpha
      interaction required the AAD alpha-helical character that also dictated
      GADD45alpha-mediated enhancement of death suppression. vMIA mutants that failed
      to interact with GADD45alpha were completely nonfunctional in cell death
      suppression, and any of the three GADD45 family members (GADD45alpha,
      GADD45beta/MyD118, or GADD45gamma/OIG37/CR6/GRP17) was able to cooperate with
      vMIA; however, none influenced cell death when introduced into cells alone.
      GADD45alpha was found to increase vMIA protein levels comparably to treatment
      with protease inhibitors MG132 and ALLN. Targeted short interfering RNA knockdown
      of all three GADD45 family members maximally reduced vMIA activity, and this
      reduction was abrogated by additional GADD45alpha. Interestingly, GADD45 family
      members were also able to bind and enhance cell death suppression by Bcl-xL, a
      member of the Bcl-2 family of cell death suppressors, suggesting a direct
      cooperative link between apoptosis and the proteins that regulate the DNA damage
      response.

PMID- 16282493
TI  - A hydrophobic domain in the large envelope protein is essential for fusion of
      duck hepatitis B virus at the late endosome.
AB  - The duck hepatitis B virus (DHBV) envelope is comprised of two transmembrane (TM)
      proteins, the large (L) and the small (S), that assemble into virions and
      subviral particles. Secondary-structure predictions indicate that L and S have
      three alpha-helical, membrane-spanning domains, with TM1 predicted to act as the
      fusion peptide following endocytosis of DHBV into the hepatocyte. We used
      bafilomycin A1 during infection of primary duck hepatocytes to show that DHBV
      must be trafficked from the early to the late endosome for fusion to occur.
      Alanine substitution mutations in TM1 of L and S, which lowered TM1
      hydrophobicity, were used to examine the role of TM1 in infectivity. The high
      hydrophobicity of the TM1 domain of L, but not of S, was shown to be essential
      for virus infection at a step downstream of receptor binding and virus
      internalization. Using wild-type and mutant synthetic peptides, we demonstrate
      that the hydrophobicity of this domain is required for the aggregation and the
      lipid mixing of phospholipid vesicles, supporting the role of TM1 as the fusion
      peptide. While lipid mixing occurred at pH 7, the kinetics of insertion of the
      fusion peptide was increased at pH 5, consistent with the location of DHBV in the
      late-endosome compartment and previous studies of the nonessential role of low pH
      for infectivity. Exchange of the TM1 of DHBV with that of hepatitis B virus
      yielded functional, infectious DHBV particles, suggesting that TM1 of all of the
      hepadnaviruses act similarly in the fusion mechanism.

PMID- 16282494
TI  - Inhibition of E2 binding to Brd4 enhances viral genome loss and phenotypic
      reversion of bovine papillomavirus-transformed cells.
AB  - The bovine papillomavirus E2 protein tethers the viral genomes to mitotic
      chromosomes in dividing cells through binding to the C-terminal domain (CTD) of
      Brd4. Expression of the Brd4-CTD competes the binding of E2 to endogenous Brd4 in
      cells. Here we extend our previous study that identified Brd4 as the E2 mitotic
      chromosome receptor to show that Brd4-CTD expression released the viral DNA from
      mitotic chromosomes in BPV-1 transformed cells. Furthermore, stable expression of
      Brd4-CTD enhanced the frequency of morphological reversion of BPV-1 transformed
      C127 cells resulting in the complete elimination of the viral DNA in the
      resulting flat revertants.

PMID- 16282492
TI  - Pathogenicity of influenza viruses with genes from the 1918 pandemic virus:
      functional roles of alveolar macrophages and neutrophils in limiting virus
      replication and mortality in mice.
AB  - The Spanish influenza pandemic of 1918 to 1919 swept the globe and resulted in
      the deaths of at least 20 million people. The basis of the pulmonary damage and
      high lethality caused by the 1918 H1N1 influenza virus remains largely unknown.
      Recombinant influenza viruses bearing the 1918 influenza virus hemagglutinin (HA)
      and neuraminidase (NA) glycoproteins were rescued in the genetic background of
      the human A/Texas/36/91 (H1N1) (1918 HA/NA:Tx/91) virus. Pathogenesis experiments
      revealed that the 1918 HA/NA:Tx/91 virus was lethal for BALB/c mice without the
      prior adaptation that is usually required for human influenza A H1N1 viruses. The
      increased mortality of 1918 HA/NA:Tx/91-infected mice was accompanied by (i)
      increased (>200-fold) viral replication, (ii) greater influx of neutrophils into
      the lung, (iii) increased numbers of alveolar macrophages (AMs), and (iv)
      increased protein expression of cytokines and chemokines in lung tissues compared
      with the levels seen for control Tx/91 virus-infected mice. Because pathological
      changes in AMs and neutrophil migration correlated with lung inflammation, we
      assessed the role of these cells in the pathogenesis associated with 1918
      HA/NA:Tx/91 virus infection. Neutrophil and/or AM depletion initiated 3 or 5 days
      after infection did not have a significant effect on the disease outcome
      following a lethal 1918 HA/NA:Tx/91 virus infection. By contrast, depletion of
      these cells before a sublethal infection with 1918 HA/NA:Tx/91 virus resulted in
      uncontrolled virus growth and mortality in mice. In addition, neutrophil and/or
      AM depletion was associated with decreased expression of cytokines and
      chemokines. These results indicate that a human influenza H1N1 virus possessing
      the 1918 HA and NA glycoproteins can induce severe lung inflammation consisting
      of AMs and neutrophils, which play a role in controlling the replication and
      spread of 1918 HA/NA:Tx/91 virus after intranasal infection of mice.

PMID- 16282495
TI  - Identification of two residues within the LDL-A module of Tva that dictate the
      altered receptor specificity of mutant subgroup A avian sarcoma and leukosis
      viruses.
AB  - Avian sarcoma and leukosis virus subgroup A (ASLV-A) entry is mediated by
      interactions between the viral glycoprotein EnvA and its cognate receptor Tva.
      Previously, some interesting mutants of ASLV-A have been selected by others which
      can use chicken Tva, but not quail Tva, for efficient entry. The mutant
      phenotypes are caused by two point mutations within the surface subunit of EnvA
      (S. L. Holmen, D. C. Melder, and M. J. Federspiel, J. Virol. 75:726-737, 2001).
      In this study, we have shown that the altered receptor specificity maps to the
      LDL-A module of Tva. Further, we have identified two residues in the chicken LDL
      A module that allow more efficient viral entry by the mutant viruses. These
      results demonstrate that the altered receptor specificity of the mutant viruses
      is determined by specific interactions with residues in the LDL-A module of Tva.

PMID- 16282496
TI  - Common ancestry of herpesviruses and tailed DNA bacteriophages.
AB  - Comparative analysis of capsid protein structures in the eukaryote-infecting
      herpesviruses (Herpesviridae) and the prokaryote-infecting tailed DNA
      bacteriophages (Caudovirales) revealed a characteristic fold that is restricted
      to these two virus lineages and is indicative of common ancestry. This fold not
      only serves as a major architectural element in capsid stability but also enables
      the conformational flexibility observed during viral assembly and maturation. On
      the basis of this and other emerging relationships, it seems increasingly likely
      that the very diverse collection of extant viruses may have arisen from a
      relatively small number of primordial progenitors.

PMID- 16282497
TI  - Breaking an absolute species barrier: transgenic mice expressing the mink PrP
      gene are susceptible to transmissible mink encephalopathy.
AB  - Transmissible mink encephalopathy (TME) is a rare disease of the North American
      mink, which has never been successfully transmitted to laboratory mice. We
      generated transgenic mice expressing the mink prion protein (PrP) and inoculated
      them with TME or the mouse-adapted scrapie strain 79A. TME infected mink PrP
      transgenic mice on a murine PrP knockout background. The absolute species barrier
      between the infectious agent of TME and mice was therefore broken. Following TME
      and 79A infection of mice carrying both mink and murine PrP(C), only proteinase
      resistant PrP homologous to the incoming agent was detectable. The presence of
      the murine PrP(C) prolonged the incubation time of TME substantially.

PMID- 16282499
TI  - Sensitization to apoptosis underlies KrasD12-dependent oncolysis of murine C26
      colorectal carcinoma cells by reovirus T3D.
AB  - Reovirus T3D is an oncolytic agent that preferentially targets tumor cells
      expressing an activated Ras oncogene. Ras signaling interferes with the cellular
      stress response that inhibits translation of reovirus RNAs. Murine C26 colorectal
      carcinoma cells express a mutant KrasD12 gene. Reovirus T3D efficiently kills C26
      cells, but not C26 cells in which the KrasD12 mRNA is stably repressed by
      expression of KrasD12-directed short-hairpin RNAs. Surprisingly, neither reovirus
      T3D protein synthesis nor T3D virus yields were suppressed by deletion of
      KrasD12. Rather, reovirus-induced tumor cell apoptosis was completely abrogated
      as a result of Kras knockdown. We conclude that sensitization of C26 tumor cells
      to reovirus-induced apoptosis underlies the Ras dependency of reovirus T3D
      oncolysis.

PMID- 16282498
TI  - Activation of p21-activated kinase 2 by human immunodeficiency virus type 1 Nef
      induces merlin phosphorylation.
AB  - The accessory human immunodeficiency virus type 1 (HIV-1) protein Nef activates
      the autophosphorylation activity of p21-activated kinase 2 (PAK2). Merlin, a
      cellular substrate of PAK2, is homologous to the ezrin-radixin-moesin family and
      plays a critical role in Rac signaling. To assess the possible impact on host
      cell metabolism of Nef-induced PAK2 activation, we investigated the
      phosphorylation of merlin in Nef expressing cells. Here we report that Nef
      induces merlin phosphorylation in multiple cell lines independently of protein
      kinase A. This intracellular phosphorylation of merlin directly correlates with
      in vitro assay of the autophosphorylation activity of Nef-activated PAK2.
      Importantly, merlin phosphorylation induced by Nef was also observed in human
      primary T cells. The finding that Nef induces phosphorylation of the key
      signaling molecule merlin suggests several possible roles for PAK2 activation in
      HIV pathogenesis.

PMID- 16282502
TI  - Evolution of cyclophilin A and TRIMCyp retrotransposition in New World primates.
AB  - Host cell factors modulate retroviral infections. Among those, cyclophilin A
      (CypA) promotes virus infectivity by facilitating virus uncoating or capsid
      unfolding or by preventing retroviral capsid interaction with cellular
      restriction factors. In Aotus species, a retrotransposed copy of CypA inserted
      into the tripartite motif 5 (TRIM5) gene encodes a fusion protein which may block
      human immunodeficiency virus type 1 by targeting the incoming virus to ubiquitin
      ligated degradation or by interfering with normal uncoating of the incoming
      particle, rendering those monkeys resistant to infection. In this study, we have
      extensively analyzed representative specimens from all New World primate genera
      and shown that the retrotransposed CypA copy is only present in Aotus. We have
      shown that this inserted copy diverged from its original counterpart and that
      this occurred prior to Aotus radiation, although no positive selection was
      observed. Finally, our data underscores the need for a precise taxonomic
      identification of primate species used as models for retroviral infections and
      novel antiviral approaches.

PMID- 16282500
TI  - Tat(28-35)SL8-specific CD8+ T lymphocytes are more effective than Gag(181-189)CM9
      specific CD8+ T lymphocytes at suppressing simian immunodeficiency virus
      replication in a functional in vitro assay.
AB  - Epitope-specific CD8+ T lymphocytes may play an important role in controlling
      human immunodeficiency virus (HIV)/simian immunodeficiency virus replication.
      Unfortunately, standard cellular assays do not measure the antiviral efficacy
      (the ability to suppress virus replication) of CD8+ T lymphocytes. Certain
      epitope-specific CD8+ T lymphocytes may be better than others at suppressing
      viral replication. We compared the antiviral efficacy of two immunodominant CD8+
      T lymphocyte responses--Tat(28-35)SL8 and Gag(181-189)CM9--by using a functional
      in vitro assay. Viral suppression by Tat-specific CD8+ T lymphocytes was
      consistently greater than that of Gag-specific CD8+ T lymphocytes. Such
      differences in antigen-specific CD8+-T-lymphocyte efficacy may be important for
      selecting CD8+ T lymphocyte epitopes for inclusion in future HIV vaccines.

PMID- 16282503
TI  - Antioxidants in the news.

PMID- 16282501
TI  - Human metapneumovirus induces a profile of lung cytokines distinct from that of
      respiratory syncytial virus.
AB  - Lung cytokine and chemokine production by BALB/c mice infected with human
      metapneumovirus (hMPV) was compared to respiratory syncytial virus (RSV)-infected
      mice. hMPV infection induced lower levels of the inflammatory cytokines
      interleukin-1 (IL-1), IL-6 and tumor necrosis factor alpha but was a more potent
      inducer of granulocyte-macrophage colony-stimulating factor and triggered a more
      sustained production of the CXC chemokine KC compared to RSV. hMPV was a stronger
      inducer of both alpha interferon (IFN-alpha) and IFN-gamma responses than RSV. In
      regard to immunomodulatory cytokines, hMPV failed to induce detectable IL-10 or
      IL-12p70 but was a potent inducer of IL-12 p40 subunit. The implications for hMPV
      pathogenesis are discussed.

PMID- 16282504
TI  - Reasons for and characteristics associated with complementary and alternative
      medicine use among adult cancer patients: a systematic review.
AB  - PURPOSE: To conduct a systematic review of reasons for and sociodemographic and
      disease characteristics associated with complementary and alternative medicine
      (CAM) use in cancer patients. METHODS: Eligible studies were identified by
      searching the following databases: Alt Health Watch, AMED, CINAHL, CancerLit,
      PremMEDLINE, MEDLINE, Pub-Med, Ingenta, EMBASE, and Health Star, as well as
      reference lists in review articles. Only English-language articles published
      between 1994 and 2004 were included. Search terms included CAM and
      oncology/cancer, decision making and CAM and oncology/cancer, treatment decision
      making and CAM and oncology/cancer, and health care choices and CAM and
      oncology/cancer. RESULTS: Fifty-two eligible studies were identified and
      summarized. These studies were conducted in 14 different countries, with the
      largest number of studies being completed in the United States (34.6%). A
      therapeutic response, wanting control, a strong belief in CAM, CAM as a last
      resort, and finding hope were the most commonly cited reasons for using CAM. Age,
      socioeconomic status, and gender were the dominant characteristics associated
      with CAM use. CONCLUSION: Reasons for and characteristics associated with CAM use
      among cancer patients have been studied extensively. Future CAM research among
      cancer patients should focus on identifying decision-making processes and
      building theoretical decision-making models. These can be used in the development
      of decisional aids for patients when confronted with the choice to use CAM as
      part of their cancer treatment.

PMID- 16282505
TI  - The effects of walking poles on shoulder function in breast cancer survivors.
AB  - Breast cancer treatment often results in impaired shoulder function, in
      particular, decrements in muscular endurance and range of motion, which may lead
      to decreased quality of life. The purpose of this investigation was to determine
      the effects of walking pole use on shoulder function in female breast cancer
      survivors. Participants had previously been treated with 1 or a combination of
      the following: mastectomy, breast conservation therapy, axillary lymph node
      dissection, chemotherapy, or radiation. Participants were randomly placed in
      experimental (n = 6) and control (n = 6) groups and met with a cancer exercise
      specialist 2 times each week for 8 weeks. The experimental group used walking
      poles during the 20-minute aerobic portion of their workout, whereas the control
      group did not use walking poles but performed 20 minutes of aerobic exercise per
      workout session. Both groups participated in similar resistance training
      programs. Testing was done pre- and postexercise intervention to determine upper
      body muscular endurance and active range of motion at the glenohumeral joint.
      Repeated-measures analysis of variance (ANOVA) revealed significant improvements
      in muscular endurance as measured by the bench press (P = .046) and lat pull down
      (P = .013) in the walking pole group. No within-group improvements were found in
      the group that did not use walking poles. The data suggest that using a walking
      pole exercise routine for 8 weeks significantly improved muscular endurance of
      the upper body, which would clearly be beneficial in helping breast cancer
      survivors perform activities of daily living and regain an independent lifestyle.

PMID- 16282506
TI  - Use of complementary therapies among breast and prostate cancer patients during
      treatment: a multisite study.
AB  - PURPOSE: The purpose of this study was to compare the use of complementary
      therapies (CT) among breast and prostate cancer patients during active cancer
      treatment. The authors compared use and beliefs about the role of CT in cancer
      recovery. METHODS: A self-report survey was completed by 126 breast cancer
      patients and 82 prostate cancer patients as part of a multisite research project.
      The self-report questionnaire inquired about the use of various CTs, sources of
      information about CT, reasons for using CT, beliefs about the benefits and risks
      of CT, demographic characteristics, and cancer treatment history. RESULTS: Most
      of the respondents were older than 50 years, Caucasian, married, had attended or
      completed college, and were less than 1 year post-diagnosis. Prostate cancer
      patients were significantly older than the breast cancer patients (P < .001).
      Several differences emerged between the groups. Compared to the prostate cancer
      patients, significantly more of the breast cancer patients reported using CT
      because they wanted to reduce the risk of recurrence (P < .01), play a more
      active role in recovery (P < .01), help manage stress (P < .01), take a more
      holistic approach (P < .01), or boost the immune system (P < .01). More of the
      prostate cancer patients reported using CT to have more control of their recovery
      (P < .05). The 2 groups also differed significantly (P < .01) on several beliefs
      about the potential benefits and risks of using CT. CONCLUSIONS: Most of the
      patients in this study had used some form of CT since the time of their
      diagnosis. Differences among breast and prostate cancer patients with regard to
      their use of CT during cancer treatment should be considered by oncology
      professionals who are discussing this topic with their patients.

PMID- 16282507
TI  - Multifocal angiostatic therapy: an update.
AB  - Multifocal angiostatic therapy (MAT) is a strategy that seeks to impede cancer
      induced angiogenesis by addressing multiple targets that regulate the angiogenic
      capacity of a cancer and/or the angiogenic responsiveness of endothelial cells,
      using measures that are preferentially, but not exclusively, nutraceutical. A
      prototype of such a regimen has been proposed previously, composed of green tea
      polyphenols, fish oil, selenium, and high-dose glycine, complementing a low-fat
      vegan diet, exercise training, and the copper-sequestering drug
      tetrathiomolybdate (TM). A review of more recent evidence suggests additional
      agents that could appropriately be included in this regimen and clarifies to some
      extent the mechanisms of action of its constituents. Diindolylmethane, a widely
      available crucifera-derived nutraceutical, has inhibited cancer growth in several
      mouse xenograft models; this effect may be largely attributable to an angiostatic
      action, as concentrations as low as 5 to 10 muM inhibit proliferation, migration,
      and tube-forming capacity of human endothelial cells in vitro, and a parenteral
      dose of 5 mg/kg markedly impairs matrigel angiogenesis in mice.
      Silymarin/silbinin, which has slowed the growth of human xenografts in a number
      of studies, suppresses the proliferation, migration, and tube-forming capacity of
      endothelial cells and inhibits vascular endothelial growth factor (VEGF)
      secretion by a range of human cancer cell lines, in concentrations that should be
      clinically feasible. The angiostatic activity of orally administered green tea
      now appears likely to reflect inhibition of the kinase activity of VEGFR-2.
      Glycine's angiostatic activity may be attributable to a hyperpolarizing effect on
      endothelial cells that decreases the activity of NADPH oxidase, now known to
      promote tyrosine kinase signaling in endothelial cells. The ability of TM to
      suppress cancer cell production of a range of angiogenic factors results at least
      in part from a down regulation of NF-kappaB activation. Dual-purpose molecular
      targets, whose inhibition could be expected to decrease the aggressiveness and
      chemoresistance of cancer cells while simultaneously impeding angiogenesis,
      include NF-kappaB, cox-2, c-Src, Stat3, and hsp90; drugs that can address these
      targets are now in development, and salicylates are notable for the fact that
      they can simultaneously inhibit NF-kappaB and cox-2. The potential complementary
      of the components of MAT should be assessed in nude mouse xenograft models.

PMID- 16282508
TI  - Expression of vascular endothelial growth factor (VEGF) and VEGF receptors in
      tumor angiogenesis and malignancies.
AB  - Angiogenesis is a process by which new blood vessels are formed from preexisting
      vessels. New blood vessel formation by angiogenesis involves the degradation of
      extra-cellular matrix combined with sprouting and migration of endothelial cells
      from preexisting capillaries. Solid tumors consist of several components,
      including normal and stromal cells, extracellular matrix, and vasculature. To
      grow and metastasize, tumors must stimulate the development of new vasculature
      through angiogenesis. Vascular endothelial growth factor (VEGF) is a potent
      angiogenic peptide with biologic effects that include regulation of hematopoietic
      stem cell development, extracellular matrix remodeling, and inflammatory cytokine
      regeneration. VEGF is both a vascular growth factor and a vascular permeability
      factor. Its expression can upregulate several proangiogenic and prometa-static
      molecules. As a central mediator of angiogenesis, VEGF has emerged as an
      important target for antiangiogenic therapy. In this review, the authors describe
      the essential characteristics of VEGF and the VEGF family of ligands and their
      receptors. They also provide an overview of the central role of VEGF in
      physiologic and pathologic angiogenesis, directly or indirectly. This review
      sheds light on the importance of VEGF-targeted antiangiogenic therapy based on
      the monoclonal antibodies against VEGF, small interfering RNA, and therapy
      directed against VEGF-VEGFR kinase. It also gives a brief overview of the natural
      products or dietary compounds that could be used as antiangiogenic agents.
      Therapeutic inhibition of vessel formation could be best suited to preventive
      strategies aimed at the suppression of angiogenesis in primary tumors in subjects
      at risk or of micrometastases after surgical removal of primary tumor.

PMID- 16282509
TI  - Protective effect of Thuja occidentalis against radiation-induced toxicity in
      mice.
AB  - The effect of Thuja occidentalis against damage induced by gamma radiation was
      studied. Whole-body exposure of Swiss albino mice to gamma-rays (6 Gy) reduced
      the total white blood cell count to 1900 cells/mm(3) on the third day, which was
      elevated to 2050 cells/mm(3) by the administration of alcoholic extract ofT
      occidentalis (5 mg/dose/animal, intraperitoneally). Six animals from each group
      were killed after 2, 7, and 11 days of irradiation to detect the bone marrow
      cellularity and radiation-induced toxicity. The number of bone marrow cells and
      alpha-esterase positive cells in control animals after 11 days was reduced to
      12.2 x 10(6) cells/femur and 693.5/4000 cells, respectively. In T occidentalis
      treated animals, bone marrow cellularity was increased to 16.9 x 10(6)
      cells/femur and alpha-esterase positive cells were 940/4000 cells, a nearly
      normal level. Alcoholic extract of T occidentalis reduced the elevated levels of
      GPT and alkaline phosphatase in liver and serum after irradiation. The lipid
      peroxidation levels were also lowered in the irradiated animals treated with the
      Thuja extract.

PMID- 16282510
TI  - Emergency ultrasound and urinalysis in the evaluation of flank pain.
AB  - OBJECTIVES: To determine the sensitivity and specificity of limited emergency
      ultrasonography of the kidney in diagnosing renal colic. METHODS: This was a
      prospective observational trial from December 2001 to December 2003 at a suburban
      emergency department. Patients who presented with flank pain suspicious for renal
      colic were enrolled. Exclusion criteria included fever, trauma, known current
      kidney stone, unstable vital signs, and inability to provide consent. All
      patients underwent sequential emergency ultrasonography and computed tomography
      of the kidneys and bladder. Data were analyzed using chi-square analysis. The
      primary outcome was the sensitivity and specificity of ultrasonography. Results
      were also stratified for presence of hematuria. RESULTS: Fifty-eight of the 104
      patients enrolled in the study were diagnosed with renal colic. The overall
      sensitivity and specificity of bedside ultrasonography for the detection of
      hydronephrosis were 86.8 (95% confidence interval [CI] = 78.8 to 92.3) and 82.4
      (95% CI = 74.1 to 88.1), respectively. In patients with hematuria, hydronephrosis
      by emergency ultrasonography demonstrated a sensitivity and specificity of 87.8
      (95% CI = 80.3 to 92.5) and 84.8 (95% CI = 73.7 to 91.9), respectively. In 55 of
      the cases, the initial computed tomograph was read by a resident and later re
      read by an attending physician. Using the reading of the attending physician as
      the criterion standard resulted in a sensitivity and specificity of 83.3 (95% CI
      = 73.2 to 88.0) and 92.0 (95% CI = 79.9 to 97.6), respectively. CONCLUSIONS:
      Emergency ultrasonography of the kidneys shows very good sensitivity and
      specificity for diagnosing renal colic in patients with flank pain and hematuria.

PMID- 16282511
TI  - Gender differences in emergency department patients with chronic obstructive
      pulmonary disease exacerbation.
AB  - OBJECTIVES: Although more men are diagnosed as having chronic obstructive
      pulmonary disease (COPD), its prevalence is increasing among women. Little is
      known about gender differences in exacerbations of COPD. The objective of this
      study was to determine if acute presentation, management, and outcomes differ
      among men and women seeking care in the emergency department (ED) for
      exacerbation of COPD. METHODS: This was a secondary analysis of a prospective
      cohort study of ED patients aged 55 years or older who presented with an
      exacerbation of COPD. Subjects underwent structured interviews in the ED and two
      weeks later. RESULTS: The cohort consisted of 397 subjects with COPD, of whom 52%
      were women. Self-report of COPD only tended to be more common among men (61% of
      men vs. 52% of women), while mixed COPD/asthma tended to be more common among
      women (39% vs. 48%; p = 0.10). Despite reporting similar chronic symptom
      severity, women were less likely than men to use anticholinergic agents before
      their ED visit (59% vs. 69%; p = 0.04). During the exacerbation, women initiated
      less home therapy and were less likely to seek emergency care within the first 24
      hours of symptom onset (25% vs. 36%; p = 0.01). Although ED care and disposition
      were similar, post-ED outcomes differed. At two-week follow-up, men were more
      likely to report an ongoing exacerbation (42% vs. 31%; p = 0.03). CONCLUSIONS:
      Men and women who present to the ED for treatment of an exacerbation of COPD have
      substantial differences in long-term medication use, self-treatment during
      exacerbation, delay in emergency care, and post-ED outcomes. Further studies are
      warranted to confirm and explain these gender-related differences.

PMID- 16282512
TI  - Addressing the systems-based practice core competency: a simulation-based
      curriculum.
AB  - Systems-based practice is one of the six core competencies implemented by the
      Accreditation Council for Graduate Medical Education to direct residency
      educational outcome assessment and accreditation. Emergency medicine-specific
      systems-based practice criteria have been described to define the expected
      knowledge and skill sets pertinent to emergency medicine practitioners. High
      fidelity patient simulation is increasingly used in graduate medical education to
      augment case-based learning. The authors describe a simulation-based curriculum
      to address the emergency medicine-specific systems-based practice core
      competency.

PMID- 16282513
TI  - Bench to bedside: Pharmacogenomics, adverse drug interactions, and the cytochrome
      P450 system.
AB  - As physicians attempt to improve the quality of health care, one area of
      particular concern has been preventable medical errors from adverse drug
      interactions. The cytochrome P450 family of enzymes has been implicated in a
      large number of these preventable, adverse drug interactions. This report reviews
      the basic biochemistry and pharmacogenomics underlying the reactions catalyzed by
      the cytochrome P450 family of enzymes. An emphasis is placed on the phenotypic
      variations within a population and the resulting clinical effects. In addition,
      six members of the cytochrome P450 superfamily that are responsible for the
      metabolism of the majority of pharmaceutical agents are profiled in detail. These
      enzymes, CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2, are reviewed with
      regard to their phenotypic variation in the population and the resulting clinical
      and therapeutic implications.

PMID- 16282514
TI  - Availability of pediatric emergency visit data from existing data sources.
AB  - OBJECTIVES: To determine the availability and completeness of selected data
      elements from administrative and clinical sources for emergency department (ED)
      visits in a national pediatric research network. METHODS: This was a
      retrospective study of 25 EDs in the Pediatric Emergency Care Applied Research
      Network. Data were obtained from two sources at each ED: 1) extant electronic
      administrative data for all visits during a 12-month period in 2002 and 2) data
      abstracted from medical records by trained abstractors for visits during ten
      randomly selected days over a three-month period in 2003. Epidemiologic data were
      obtained for all visits and additional clinical data for patients with two target
      conditions: asthma and fractures. RESULTS: A total of 749,036 visits were
      analyzed from administrative sources and 12,756 medical records abstracted. Data
      availability varied by element, method of capture, and site. From administrative
      sources, data on insurance type were the most complete (1.3% overall missing;
      range, 0%-18.5% for individual sites), whereas mode of arrival (25.5% missing)
      and triage time (65.3%) were the least complete. Disposition was missing in only
      1.2% of medical records overall (range, 0%-5%) and diagnosis was missing in 3%
      (range, 0%-16%); these were missing from 14.4% and 10.5%, respectively, of
      administrative sources. Among visits with injury diagnoses, E-codes were missing
      in 27% of cases. For patients with asthma (n = 861), documentation of specific
      elements of the clinical examination by nurses and physicians was also variable.
      CONCLUSIONS: Data elements important in emergency medical care for children are
      frequently missing in existing administrative and medical record sources;
      completeness varies widely across EDs. Researchers must be aware of these
      limitations in the use of existing data when planning studies.

PMID- 16282515
TI  - Reasons for using the emergency department: results of the EMPATH Study.
AB  - OBJECTIVES: Emergency Medicine Patients' Access To Healthcare (EMPATH) was a
      cross-sectional, observational study conducted to identify the principal reasons
      why patients seek care in hospital emergency departments (EDs) in the United
      States. METHODS: Twenty-eight U.S. hospitals, stratified by geographic region and
      hospital characteristics, participated in this study. Demographic, clinical, and
      insurance data were collected for a 24-hour period at each site, using chart
      reviews and a structured interview administered to all consenting adult patients
      seeking treatment during that period. Patients' reasons for presenting to the ED
      were assessed by their level of agreement (on a three-point Likert scale) with 21
      carefully worded statements designed to capture a range of possible reasons for
      seeking care in the ED. Factor analysis was used to consolidate highly correlated
      responses and to identify the principal factors explaining patients' reasons for
      coming to the ED. RESULTS: A total of 1,579 patient interviews and 2,004 chart
      reviews were obtained from a diverse sample that was 55.4% female, 58.3% white,
      28.3% African American, 7.0% Hispanic, and 6.0% other ethnic groups. This
      exploratory analysis yielded five factors characterizing patients' principal
      reasons for seeking ED care, with medical necessity the most frequent, followed
      by ED preference, convenience, affordability, and limitations of insurance.
      CONCLUSIONS: Use of the ED is, for most people, an affirmative choice over other
      providers rather than a last resort; it is often a choice driven by lack of
      access to or dissatisfaction with other sources of care.

PMID- 16282516
TI  - The effect of ethanol on uncontrolled hemorrhage in a rodent model.
AB  - OBJECTIVES: Ethanol intoxication has hemodynamic and metabolic effects after
      hemorrhage according to studies using fixed-volume controlled blood loss models.
      The authors tested the null hypothesis that after uncontrolled hemorrhage there
      would be no difference in the hemodynamic responses between ethanol-intoxicated
      (EtOH+) and nonintoxicated (EtOH-) rats. METHODS: Forty Sprague-Dawley rats were
      anesthetized with althesin intraperitoneally. Twenty EtOH+ rats received a 3-g/kg
      dose of 20% ethanol intraperitoneally 60 minutes before hemorrhage. The EtOH-
      rats received an equivalent volume of normal saline intraperitoneally. The
      femoral artery was cannulated by cutdown to monitor the mean arterial blood
      pressure (MAP) and to obtain blood samples for lactate (LAC). Twenty rats (ten
      EtOH+ and ten EtOH-) underwent uncontrolled hemorrhage by 75% tail amputation.
      Twenty rats (ten EtOH+ and ten EtOH-) served as nonhemorrhage controls. The MAP,
      LAC, and cumulative hemorrhage volume were measured prehemorrhage and then every
      15 minutes posthemorrhage for 120 minutes. Data were reported as mean +/- SEM.
      Group comparisons were analyzed by analysis of variance with repeated values and
      post hoc testing by Bonferroni (two tailed; alpha = 0.05). RESULTS: Initially,
      EtOH+ and EtOH- rats were evenly matched for LAC and MAP. The mean (+/-SD)
      baseline ethanol level was 170 (+/-68) mg/dL in EtOH+ rats. Cumulative hemorrhage
      volume was similar (p = 0.23) for the EtOH- (2.36 +/- 0.24 mL/100 g) and EtOH+
      (1.87 +/- 0.32 mL/100 g) rats. No significant difference was noted in
      posthemorrhage MAP between EtOH- (68.6 +/- 6.8 mm Hg) and EtOH+ (69.3 +/- 7.2 mm
      Hg) rats (p = 1.00). The EtOH- group had a significantly higher LAC (4.94 +/-
      1.07 mmol/L) than the EtOH+ group (2.27 +/- 0.59 mmol/L) (p < 0.03). CONCLUSIONS:
      Ethanol intoxication does not deleteriously affect the hemodynamic response to
      uncontrolled hemorrhage.

PMID- 16282517
TI  - Management of acute undifferentiated agitation in the emergency department: a
      randomized double-blind trial of droperidol, ziprasidone, and midazolam.
AB  - OBJECTIVES: To compare the efficacy of sedation, need for rescue sedation, rates
      of respiratory depression, and complications of droperidol, ziprasidone, and
      midazolam when used for the treatment of emergency department (ED) patients
      requiring sedation for acute undifferentiated agitation. METHODS: A prospective,
      randomized, double-blind trial of agitated ED patients requiring emergent
      sedation was performed. Patients were randomized to receive droperidol 5 mg,
      ziprasidone 20 mg, or midazolam 5 mg intramuscularly. Interval measurements were
      made at 0, 15, 30, 45, 60, and 120 minutes and included Altered Mental Status
      Scale (AMS) scores, oxygen saturations, and end-tidal carbon dioxide levels.
      RESULTS: A total of 144 patients were enrolled; 50 patients received droperidol,
      46 received ziprasidone, and 48 received midazolam. Adequate sedation (mean AMS
      score <0) was achieved at 15 minutes in patients receiving midazolam (mean AMS
      score, -0.81) and 30 minutes for patients receiving droperidol (mean AMS score, 
      1.3) and ziprasidone (mean AMS score, -0.74). Rescue medication for sedation was
      necessary in 38 of 144 patients (droperidol, 5 of 50; ziprasidone, 9 of 46;
      midazolam, 24 of 48; p < 0.05). No cardiac dysrhythmias were identified in any
      treatment group. Respiratory depression that clinically required treatment with
      supplemental oxygen occurred in 21 of 144 patients (droperidol, 4 of 50;
      ziprasidone, 7 of 46; midazolam, 10 of 48; p = 0.20). No patients required
      endotracheal intubation. CONCLUSIONS: Acutely agitated ED patients sedated with
      droperidol or ziprasidone required rescue medications to achieve adequate
      sedation less frequently than those sedated with midazolam. The onset of adequate
      sedation is delayed with ziprasidone, relative to the other agents.

PMID- 16282518
TI  - Functional properties of internalization-deficient P2X4 receptors reveal a novel
      mechanism of ligand-gated channel facilitation by ivermectin.
AB  - Although P2X receptors within the central nervous system mediate excitatory ATP
      synaptic transmission, the identity of central ATP-gated channels has not yet
      been elucidated. P2X(4), the most widely expressed subunit in the brain, was
      previously shown to undergo clathrin-dependent constitutive internalization by
      direct interaction between activator protein (AP)2 adaptors and a tyrosine-based
      sorting signal specifically present in the cytosolic C-terminal tail of mammalian
      P2X(4) sequences. In this study, we first used internalization-deficient P2X(4)
      receptor mutants to show that suppression of the endocytosis motif significantly
      increased the apparent sensitivity to ATP and the ionic permeability of P2X(4)
      channels. These unique properties, observed at low channel density, suggest that
      interactions with AP2 complexes may modulate the function of P2X(4) receptors. In
      addition, ivermectin, an allosteric modulator of several receptor channels,
      including mammalian P2X(4), did not potentiate the maximal current of
      internalization-deficient rat or human P2X(4) receptors. We demonstrated that
      binding of ivermectin onto wild-type P2X(4) channels increased the fraction of
      plasma membrane P2X(4) receptors, whereas surface expression of internalization
      deficient P2X(4) receptors remained unchanged. Disruption of the clathrin
      mediated endocytosis with the dominant-negative mutants Eps15 or AP-50 abolished
      the ivermectin potentiation of wild-type P2X(4) channel currents. Likewise,
      ivermectin increased the membrane fraction of nicotinic alpha7 acetylcholine
      (nalpha7ACh) receptors and the potentiation of acetylcholine current by
      ivermectin was suppressed when the same dominant-negative mutants were expressed.
      These data showed that potentiation by ivermectin of both P2X(4) and nalpha7ACh
      receptors was primarily caused by an increase in the number of cell surface
      receptors resulting from a mechanism dependent on clathrin/AP2-mediated
      endocytosis.

PMID- 16282519
TI  - High-affinity, slowly desensitizing GABAA receptors mediate tonic inhibition in
      hippocampal dentate granule cells.
AB  - The tonic form of GABA-mediated inhibition requires the presence of slowly
      desensitizing GABA(A) receptors with high affinity, which has not yet been
      directly demonstrated in hippocampal neurons. Low concentration of GABA (1
      microM) persistently increased baseline noise, increased membrane slope
      conductance, but did not affect spontaneous inhibitory postsynaptic currents
      (sIPSCs) in dentate granule cells (DGCs). Higher concentrations of GABA (10-100
      microM) desensitized synaptic currents quickly, and there was a large residual
      current. Saturating concentration of GABA (1 mM) completely desensitized synaptic
      currents and revealed a slowly desensitizing, persistent current. Penicillin (300
      microM) inhibited baseline noise without affecting mean current and inhibited
      decay time of sIPSCs. GABA(A) receptors mediating baseline noise in DGCs were
      sensitive to allopregnanolone, furosemide, and loreclezole and insensitive to
      diazepam and zolpidem. These studies demonstrate persistently open GABA(A)
      receptors on DGCs with high affinity for GABA, slow desensitization rate, and
      pharmacological properties similar to those of recombinant receptors containing
      alpha(4), beta(1), and the delta subunits.

PMID- 16282520
TI  - Acquired cadmium resistance in metallothionein-I/II(-/-) knockout cells: role of
      the T-type calcium channel Cacnalpha1G in cadmium uptake.
AB  - Metallothioneins (MTs) are cytoplasmic proteins that sequester certain divalent
      cations and are considered a primary cellular defense against the toxic
      transition metal cadmium (Cd(2+)). MT-I/II(-/-) knockout [MT(-/-)] cells are
      available and serve as an excellent tool to study non-MT-related mechanisms in
      metal tolerance. In the current study, Cd(2+)-resistant MT(-/-) (CdR) and CdR
      revertant (CdR-rev) cell lines were developed and characterized to investigate
      non-MT-mediated cellular protection mechanisms. Resistance to Cd(2+) was
      approximately 70-fold higher in CdR than the parental MT(-/-) cell line (IC(50) =
      20 versus 0.3 microM, respectively) and was stable in the absence of Cd(2+) for
      35 days. Accumulation of Cd(2+) by the CdR cell line was reduced by approximately
      95% compared with parental cells, primarily because of a decreased Cd(2+) uptake.
      Cd(2+) uptake by the MT(-/-) parental cell line was independent of sodium,
      energy, and electrogenic potential. Uptake was saturable (K(m) = 65 nM; V(max) =
      4.9 pmol/mg/min) and pH-dependent (maximal at pH 6.5-7). Potent inhibitors of
      Cd(2+) uptake included Zn(2+) (IC(50) = 7 microM), Mn(2+) (IC(50) = 0.4 microM),
      and the T-type Ca(2+) channel antagonist mibefradil (IC(50) = 5 microM), whereas
      other metals (including Fe(2+)) and L-type Ca(2+) channel antagonists had little
      effect. Immunoblot and real-time reverse transcription-polymerase chain reaction
      analysis indicated that the Cacnalpha(1G) T-type Ca(2+) channel was expressed at
      a reduced level in CdR compared with the parental MT(-/-) cell line, suggesting
      it is important for Cd(2+) uptake. The CdR1-rev cell line was found to have a
      Cd(2+) uptake and sensitivity level in between that of the CdR1 and MT(-/-) cell
      lines. Consistent with this was an intermediate expression of Cacnalpha(1G) in
      the CdR-rev cell line. These data suggest that decreased expression of
      Cacnalpha(1G) protects cells from Cd(2+) exposure by limiting Cd(2+) uptake.

PMID- 16282521
TI  - Advantages for transdermal over oral oxybutynin to treat overactive bladder:
      Muscarinic receptor binding, plasma drug concentration, and salivary secretion.
AB  - To clarify pharmacological usefulness of transdermal oxybutynin in the therapy of
      overactive bladder, we have characterized muscarinic receptor binding in rat
      tissues with measurement of plasma concentrations of oxybutynin and its
      metabolite N-desethyl-oxybutynin (DEOB) and salivation after transdermal
      oxybutynin compared with oral route. At 1 and 3 h after oral administration of
      oxybutynin, there was a significant increase in apparent dissociation constant
      (Kd) for specific [N-methyl-3H]scopolamine ([3H]NMS) binding in the rat bladder,
      submaxillary gland, heart, and colon compared with control values. Concomitantly,
      submaxillary gland and heart showed a significant decrease in maximal number of
      binding sites (Bmax) for [3H]NMS binding, which lasted until 24 h. Transdermal
      application of oxybutynin caused dose-dependent increases in Kd values for
      specific [3H]NMS binding in rat tissues. The increment of Kd values by
      transdermal oxybutynin was dependent on the application time. Plasma
      concentrations of oxybutynin and DEOB peaked at 1 h after oral oxybutynin. In
      contrast, plasma concentrations of oxybutynin increased slowly, depending on the
      transdermal application time of this drug until 12 h. Suppression of pilocarpine
      induced salivation in rats due to transdermal oxybutynin was significantly weaker
      and more reversible than that by oral oxybutynin, which abolished salivary
      secretion. The present study has shown that transdermal oxybutynin binds
      significantly to rat bladder muscarinic receptors without producing both long
      lasting occupation of exocrine receptors and cessation of cholinergic salivation
      evoked by oral oxybutynin. Thus, the present study provides further
      pharmacological basis for advantage of transdermal over oral oxybutynin in the
      therapy of overactive bladder.

PMID- 16282522
TI  - Brain cholesterol synthesis in mice is affected by high dose of simvastatin but
      not of pravastatin.
AB  - On a global scale, there is an increasing tendency for a more aggressive
      treatment of hypercholesterolemia. Minor effects of statins on brain cholesterol
      metabolism have been reported in some in vivo animal studies, and it seems that
      this is due to a local effect of the drug. We treated male mice of the inbred
      strain C57/BL6 with a high daily dose of lipophilic simvastatin (100 mg/kg b.wt.)
      or hydrophilic pravastatin (200 mg/kg b.wt.) or vehicle (controls) by oral gavage
      for 3 days. To compare the impact of both statins on brain cholesterol synthesis
      and degradation, levels of cholesterol, its precursor lathosterol, and its brain
      metabolite 24(S)-hydroxycholesterol as well as statin concentrations were
      determined in whole-brain lipid extracts using mass spectrometry. The expression
      of 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase mRNA and of other
      target genes were evaluated using real-time reverse transcription-polymerase
      chain reaction. In addition, analysis of liver and serum samples was performed.
      Similar levels of simvastatin and pravastatin were detected in whole-brain
      homogenates. Cholesterol contents in the brain, liver, and serum were not
      affected by high-dose statin treatment. Whereas brain cholesterol precursor
      levels were reduced in simvastatin-treated animals only, no effect was observed
      on the formation of the brain cholesterol metabolite, 24(S)-hydroxycholesterol.
      Polymerase chain reaction analysis revealed that mRNA expression of HMG-CoA
      reductase and ATP-binding cassette transporter A1 in the brain was significantly
      up-regulated in simvastatin-treated animals compared with pravastatin-treated or
      control animals. We conclude that, under the present experimental conditions,
      brain cholesterol synthesis is significantly affected by short-term treatment
      with high doses of lipophilic simvastatin, whereas whole-brain cholesterol
      turnover is not disturbed.

PMID- 16282523
TI  - Angiotensin I-converting enzyme inhibitors block protein kinase C epsilon by
      activating bradykinin B1 receptors in human endothelial cells.
AB  - Angiotensin I-converting enzyme (ACE) inhibitors are widely used to treat
      patients with cardiovascular and kidney diseases, but inhibition of ACE alone
      does not fully explain the beneficial effects. We reported that ACE inhibitors
      directly activate bradykinin B1 receptor at the canonical Zn2+ binding site,
      leading to prolonged nitric oxide (NO) production in endothelial cells. Protein
      kinase C (PKC) epsilon, a novel PKC isoform, is up-regulated in myocardium after
      infarction, suggesting a role in the development of cardiac dysfunction. In
      cytokine-treated human lung microvascular endothelial cells, B1 receptor
      activation by ACE inhibitors (enalaprilat, quinaprilat) or peptide ligands (des
      Arg10-Lys1-bradykinin, des-Arg9-bradykinin) inhibited PKC epsilon with an IC50 =
      7 x 10(-9) M. Despite the reported differences in binding affinity to receptor,
      the two peptide ligands were equally active, even when inhibitor blocked the
      cleavage of Lys(1), thus the conversion by aminopeptidase. The synthetic
      undecapeptide (LLPHEAWHFAR) representing the binding site for ACE inhibitors on
      human B(1) receptors reduced PKC epsilon inhibition by enalaprilat but not by
      peptide agonist. A combination of inducible and endothelial NO synthase
      inhibitors, 1400W [N-(3(aminomethyl) benzyl) acetamidine dihydrochloride] and N
      omega-nitro-L-arginine (2 microM), significantly reduced inhibition by
      enalaprilat (100 nM), whereas the NO donor (Z)-1-[N-(2-aminoethyl)-N-(2
      ammonioethyl) amino]diazen-1-ium-1,2-diolate (100 microM) inhibited PKC epsilon
      activity just as the B1 ligands did. In conclusion, NO generated by B1 receptor
      activation inhibits PKC epsilon.

PMID- 16282524
TI  - Real-time observation of molecular motion on a surface.
AB  - The laser-induced movement of CO molecules over a platinum surface was followed
      in real time by means of ultrafast vibrational spectroscopy. Because the CO
      molecules bound on different surface sites exhibit different C-O stretch
      vibrational frequencies, the site-to-site hopping, triggered by excitation with a
      laser pulse, can be determined from subpicosecond changes in the vibrational
      spectra. The unexpectedly fast motion--characterized by a 500-femtosecond time
      constant--reveals that a rotational motion of the CO molecules, rather than pure
      translation, is required for this diffusion process. This conclusion is
      corroborated by density functional theory calculations.

PMID- 16282525
TI  - A role for the phagosome in cytokine secretion.
AB  - Membrane traffic in activated macrophages is required for two critical events in
      innate immunity: proinflammatory cytokine secretion and phagocytosis of
      pathogens. We found a joint trafficking pathway linking both actions, which may
      economize membrane transport and augment the immune response. Tumor necrosis
      factor alpha (TNFalpha) is trafficked from the Golgi to the recycling endosome
      (RE), where vesicle-associated membrane protein 3 mediates its delivery to the
      cell surface at the site of phagocytic cup formation. Fusion of the RE at the cup
      simultaneously allows rapid release of TNFalpha and expands the membrane for
      phagocytosis.

PMID- 16282527
TI  - Mach-Zehnder interferometry in a strongly driven superconducting qubit.
AB  - We demonstrate Mach-Zehnder-type interferometry in a superconducting flux qubit.
      The qubit is a tunable artificial atom, the ground and excited states of which
      exhibit an avoided crossing. Strongly driving the qubit with harmonic excitation
      sweeps it through the avoided crossing two times per period. Because the induced
      Landau-Zener transitions act as coherent beamsplitters, the accumulated phase
      between transitions, which varies with microwave amplitude, results in quantum
      interference fringes for n = 1 to 20 photon transitions. The generalization of
      optical Mach-Zehnder interferometry, performed in qubit phase space, provides an
      alternative means to manipulate and characterize the qubit in the strongly driven
      regime.

PMID- 16282526
TI  - An unusual marine crocodyliform from the Jurassic-Cretaceous boundary of
      Patagonia.
AB  - Remains of the marine crocodyliform Dakosaurus andiniensis from western South
      America reveal a lineage that drastically deviated from the skull morphology that
      characterizes marine crocodyliforms. The snout and lower jaw are extremely
      robust, short, and high and only bear a few large teeth with serrated edges
      (resembling those of some terrestrial carnivorous archosaurs). This unusual
      morphology contrasts with the long and gracile snout and lower jaws bearing
      numerous teeth, which are present in the closest relatives of D. andiniensis (and
      interpreted as indicating feeding on small fish or mollusks). Thus, the
      morphological diversity of pelagic marine crocodyliforms was wider than had been
      thought.

PMID- 16282531
TI  - One- and two-sample nonparametric inference procedures in the presence of a
      mixture of independent and dependent censoring.
AB  - In survival analysis, the event time T is often subject to dependent censorship.
      Without assuming a parametric model between the failure and censoring times, the
      parameter Theta of interest, for example, the survival function of T, is
      generally not identifiable. On the other hand, the collection Omega of all
      attainable values for Theta may be well defined. In this article, we present
      nonparametric inference procedures for Omega in the presence of a mixture of
      dependent and independent censoring variables. By varying the criteria of
      classifying censoring to the dependent or independent category, our proposals can
      be quite useful for the so-called sensitivity analysis of censored failure times.
      The case that the failure time is subject to possibly dependent interval
      censorship is also discussed in this article. The new proposals are illustrated
      with data from two clinical studies on HIV-related diseases.

PMID- 16282532
TI  - Mast cells, which interact with Escherichia coli, up-regulate genes associated
      with innate immunity and become less responsive to Fc(epsilon)RI-mediated
      activation.
AB  - Mast cells, which are associated with T helper cell type 2-dependent
      inflammation, have now been implicated in the innate immune response. To further
      characterize how mast cells are programmed to respond to infectious organisms, we
      used expression profiling using DNA microarray analysis of gene expression by
      human mast cells (huMC) during ingestion of Escherichia coli and examined
      immunoglobulin E (IgE)-mediated degranulation. Analysis of data revealed that
      specific groups of genes were modulated, including genes encoding transcription
      factors, cell signaling molecules, cell cycle regulators, enzymes, cytokines,
      novel chemokines of the CC family, adhesion molecules, and costimulatory
      molecules. Enzyme-linked immunosorbent assay analysis confirmed the production of
      tumor necrosis factor and the chemokines CC chemokine ligand (CCL)-1/I-309, CCL
      19/macrophage-inflammatory protein-3beta (MIP-3beta), and CCL-18/MIP-4; flow
      cytometry confirmed the up-regulation of carcinoembryonic antigen-related cell
      adhesion molecule 1, the integrin CD49d, and CD80. Coincubation with E. coli down
      regulated Fc receptor for IgE I (FcepsilonRI) expression and FcepsilonRI-mediated
      huMC degranulation. These data are consistent with the concept that bacterial
      exposure directs mast cell responses toward innate immunity and away from IgE
      mediated effects.

PMID- 16282533
TI  - HIV-1 TAT represses transcription of the bone morphogenic protein receptor-2 in
      U937 monocytic cells.
AB  - The bone morphogenetic protein receptor-2 (BMPR2) is a member of the transforming
      growth factor-beta receptor family and is expressed on the surface of several
      cell types including endothelial cells and macrophages. Recently, a cause for
      familial primary pulmonary hypertension (FPPH) has been identified as mutations
      in the gene encoding BMPR2. Three forms of pulmonary hypertension (PH) exist,
      including PPH, FPPH, and PH secondary to other etiologies (sporadic PH) such as
      drug abuse and human immunodeficiency virus (HIV) infection. It is interesting
      that these subtypes are histologically indistinguishable. The macrophage is a key
      target cell for HIV-1, significantly altering macrophage cell function upon
      infection. HIV-1 trans-activator of transcription (Tat), an immediate-early
      product of the HIV-1 lifecycle, plays an important role in mediating HIV-induced
      modulation of host cell function. Our laboratory has previously shown that Tat
      represses mannose receptor transcription in macrophages. In the current study, we
      examined activity from the BMPR2 promoter in the macrophage cell line U937 and
      potential regulation by Tat. Transfection of U937 cells with BMPR2 promoter
      reporter constructs revealed dose-dependent repression of BMPR2 promoter activity
      in the presence of Tat. Experiments using truncations of the BMPR2 promoter
      localized Tat-mediated repression to the first 208 bases of the promoter.
      Decreased BMPR2 transcription resulted in altered downstream signaling. Similar
      to mothers against decapentaplegics (SMAD) phosphorylation and SMAD6 expression,
      in response to BMP2 treatment, were down-regulated after Tat treatment. Finally,
      HIV-1 infection and treatment with Tat protein of the U937 human monocytic cell
      line resulted in a decreased, endogenous BMPR2 transcript copy number.

PMID- 16282534
TI  - CD16+ monocytes in human cutaneous leishmaniasis: increased ex vivo levels and
      correlation with clinical data.
AB  - Peripheral blood CD16 (Fc receptor for immunoglobulin G III)-positive monocytes
      have been shown to expand in different pathological conditions, such as cancer,
      asthma, sepsis, human immunodeficiency virus infection, and AIDS progression, but
      data in leishmaniasis are lacking. We found that cutaneous leishmaniasis patients
      (n = 15) displayed a significant increase in the percentage (3.5 vs. 10.1) as
      well as mean fluorescent intensity (13.5 vs. 29.2) of ex vivo CD16 expression in
      monocytes as compared with healthy controls. We observed a significant positive
      correlation between the percentage of ex vivo CD16+ monocytes and lesion size (P
      = 0.0052, r = 0.75) or active transforming growth factor-beta plasma levels (P =
      0.0017, r = 0.78). In addition, two patients with nonhealing lesions during a 3
      year follow-up had high (9.1-19.4%) CD16 levels at diagnosis. Our data suggest a
      deleterious role for CD16 in human leishmaniasis, as well as its possible use as
      a marker for disease severity and/or adverse disease outcome.

PMID- 16282535
TI  - First-ever stroke incidence and 30-day case fatality in the Sicilian Aeolian
      archipelago, Italy.
AB  - BACKGROUND AND PURPOSE: Not many data on stroke epidemiology come from studies on
      islands. This is the first report on a Mediterranean archipelago population.
      METHODS: Using recommended criteria, from July 1, 1999, to June 30, 2002,
      information was collected on first-ever stroke and 30-day case fatality in
      Aeolian island residents (13,431). RESULTS: The overall crude incidence rate was
      154 of 100,000 (95% CI, 118 to 197; 128 in men and 180 in women) or 180, 154, and
      87, if adjusted to the Italian, European, and world populations, respectively.
      The 30-day case fatality rate was 24.2% (95% CI, 14.22 to 36.75). CONCLUSIONS:
      Besides genetic or dietary factors, our results may reflect local, limited
      possibilities of diagnosis and management for stroke patients.

PMID- 16282536
TI  - Identification of culprit lesions after transient ischemic attack by combined 18F
      fluorodeoxyglucose positron-emission tomography and high-resolution magnetic
      resonance imaging.
AB  - BACKGROUND AND PURPOSE: Carotid endarterectomy is currently guided by
      angiographic appearance on the assumption that the most stenotic lesion visible
      at angiography is likely to be the lesion from which future embolic events will
      arise. However, risk of plaque rupture, the most common cause of atherosclerosis
      related thromboembolism, is dictated by the composition of the plaque, in
      particular the degree of inflammation. Angiography may, therefore, be an
      unreliable method of identifying vulnerable plaques. In this study, plaque
      inflammation was quantified before endarterectomy using the combination of 18F
      fluorodeoxyglucose positron (FDG)-emission tomography (PET) and high-resolution
      MRI (HRMRI). METHODS: Twelve patients, all of whom had suffered a recent
      transient ischemic attack, had a severe stenosis in the ipsilateral carotid
      artery, and were awaiting carotid endarterectomy underwent FDG-PET and HRMRI
      scanning. A semiquantitative estimate of plaque inflammation was calculated for
      all of the lesions identified on HRMRI. RESULTS: In 7 of 12 patients (58%), high
      FDG uptake was seen in the lesion targeted for endarterectomy. In the remaining 5
      patients, FDG uptake in the targeted lesion was low. In these 5 patients, 3 had
      nonstenotic lesions identified on HRMRI that exhibited a high level of FDG
      uptake. All 3 of the highly inflamed nonstenotic lesions were located in a
      vascular territory compatible with the patients' presenting symptoms.
      CONCLUSIONS: Our data suggest that angiography may not always identify the
      culprit lesion. Combined FDG-PET and HRMRI can assess the degree of inflammation
      in stenotic and nonstenotic plaques and could potentially be used to identify
      lesions responsible for embolic events.

PMID- 16282537
TI  - The vulnerable carotid artery plaque: current imaging methods and new
      perspectives.
AB  - BACKGROUND AND PURPOSE: Atherosclerosis is a diffuse, chronic inflammatory
      disorder that involves the vascular, metabolic, and immune systems and leads to
      plaque vulnerability. The traditional risk assessment relies on clinical,
      biological, and conventional imaging tools. However, these tools fall short in
      predicting near-future events in patients with vulnerable carotid artery plaque.
      METHODS: In current clinical practice, anatomic imaging modalities, such as B
      mode ultrasound, spiral computed tomography angiography, and high-resolution MRI,
      can identify several morphological features characteristic of the vulnerable
      plaque but give little or no information regarding molecular and cellular
      mechanisms. RESULTS: This review is dedicated to factors involved in carotid
      artery plaque vulnerability and to new imaging methods that target this
      condition. Our aim is to describe the following: (1) conventional pathologic and
      imaging markers predictive of plaque vulnerability; (2) the role of relevant
      biological, genetic, and mechanical factors; (3) the potential of new imaging
      methods; and (4) current and emerging treatments. CONCLUSIONS: A multimodal
      assessment of plaque vulnerability involving the combination of systemic markers,
      new imaging methods that target inflammatory and thrombotic components, and the
      potential of emerging therapies may lead to a new stratification system for
      atherothrombotic risk and to a better prevention of atherothrombotic stroke.

PMID- 16282538
TI  - The impact of history of hypertension and type 2 diabetes at baseline on the
      incidence of stroke and stroke mortality.
AB  - BACKGROUND AND PURPOSE: Both hypertension and diabetes are strong predictors of
      stroke, but very few studies have assessed their joint effect on stroke risk. We
      evaluated prospectively the joint association of history of hypertension and type
      2 diabetes on the incidence of stroke and stroke mortality. METHODS: We
      prospectively followed 49,582 Finnish subjects aged 25 to 74 years without a
      history of stroke and coronary heart disease at baseline. Hazards ratios (HRs)
      for stroke risk were estimated by the hypertension and diabetes status. RESULTS:
      During a mean follow-up of 19.1 years, 2978 incident stroke events were recorded,
      of which 924 were fatal. Age-, sex-, and study year-adjusted HRs of stroke
      incidence were 1.35 (95% CI, 1.21 to 1.51), 1.98 (95% CI, 1.79 to 2.19), 2.54
      (95% CI, 1.61 to 4.01), 3.51 (95% CI, 2.40 to 5.14), and 4.50 (95% CI, 3.60 to
      5.61), respectively, among subjects with hypertension I (blood pressure 140 to
      159/90 to 94 mm Hg) only, with hypertension II (blood pressure > or =160/95 mm
      Hg, or using antihypertensive drugs) only, with diabetes only, with both
      hypertension I and diabetes, and with both hypertension II and diabetes compared
      with the subjects without either of the diseases. The corresponding HRs of stroke
      mortality were 1.47, 2.62, 3.06, 5.59, and 9.27, respectively. Additional
      adjustments for body mass index, cholesterol, education, smoking, alcohol
      consumption, and physical activity did not appreciably change these risk
      estimates. Blood pressure affected the risk of stroke similarly in diabetic and
      nondiabetic subjects. CONCLUSIONS: Hypertension and type 2 diabetes increase
      stroke risk independently, and their combination increases the risk drastically.
      A significant proportion of the risk of stroke assumed to be related to
      hypertension may be attributable to concomitant diabetes.

PMID- 16282539
TI  - Drug-eluting stents for the treatment of intracranial atherosclerosis: initial
      experience and midterm angiographic follow-up.
AB  - BACKGROUND AND PURPOSE: Intracranial stenting is associated with a 32% rate of
      restenosis. Drug-eluting stents (DES) have revolutionized the treatment of
      coronary artery disease and have greatly reduced the risk of in-stent stenosis.
      We present our experience with the feasibility and safety of using DES for
      patients with symptomatic intracranial atherosclerosis. METHODS: All of the
      patients had >70% stenoses and had failed maximal medical therapy. They were
      pretreated with aspirin, clopidogrel, and intraprocedural heparin. All of the
      lesions were predilated, and balloons and stents were slightly undersized.
      Clopidogrel and aspirin were continued for 1 year, and patients had clinical
      follow-up and vascular imaging at 30 days, 6 months, and 1 year. RESULTS: Eight
      patients with intracranial internal carotid artery (3), middle cerebral (2),
      basilar (2), and vertebral artery (1) stenoses were successfully treated with 4
      Cypher (Cordis Corp) and 4 Taxus (Boston Scientific Inc) stents. The mean
      stenosis severity was reduced from 84.4%+/-10.2% to 2.5%+/-4.6%. One patient had
      an intraprocedural retinal embolism, but there were no other complications. Over
      a mean follow-up of 11.1+/-4.9 months (range, 2 to 17.3 months), patients have
      had repeat angiography (5) or transcranial Doppler with or without CT angiography
      (3). None of the patients have had clinical or significant angiographic
      restenosis or required target vessel revascularization. CONCLUSIONS: Elective
      intracranial stenting with DES appears to be feasible and safe, but additional
      clinical experience is required to assess its efficacy.

PMID- 16282540
TI  - Predicting improvement in gait after stroke: a longitudinal prospective study.
AB  - BACKGROUND AND PURPOSE: To study the longitudinal relationship of functional
      change in walking ability and change in time-dependent covariates and to develop
      a multivariate regression model to predict longitudinal change of walking
      ability. METHODS: A total of 101 acute stroke patients with first-ever ischemic
      middle cerebral artery strokes was used as the population. Prospective cohort
      study based on 18 repeated measurements over time during the first poststroke
      year. Baseline characteristics as well as longitudinal information from
      functional ambulation categories (FAC), Fugl-Meyer leg score (FM-leg), Motricity
      index leg score (MI-leg), letter cancellation task (LCT), Fugl-Meyer balance (FM
      balance), and timed balance test (TBT) were obtained. Intervention consisted of a
      basic rehabilitation program with additional arm, leg, or air splint therapy.
      Main outcome measure constituted change scores on FAC over time. RESULTS: In
      total, 1532 of the 1717 change scores were available for regression analysis. The
      regression model showed that TBT change scores were the most important factor in
      predicting improvement on FAC (beta=0.094; P<0.001) followed by changes scores on
      FM-leg (beta=0.014; P<0.001) and reduction in LCT omissions (beta=-0.010;
      P<0.001) and MI leg test (beta=0.001; P<0.001). In addition, time itself was
      significantly negatively associated with improvement (beta=-0.002; P<0.001).
      CONCLUSIONS: Improvement in standing balance control is more important than
      improvement in leg strength or synergism to achieve improvement in walking
      ability, whereas reduction in visuospatial inattention is independently related
      to improvement of gait. Finally, time itself is an independent covariate that is
      negatively associated with change on FAC, suggesting that most pronounced
      improvements occur earlier after stroke.

PMID- 16282541
TI  - Risk factors for subarachnoid hemorrhage: an updated systematic review of
      epidemiological studies.
AB  - BACKGROUND AND PURPOSE: After a 1996 review from our group on risk factors for
      subarachnoid hemorrhage (SAH), much new information has become available. This
      article provides an updated overview of risk factors for SAH. METHODS: An
      overview of all longitudinal and case-control studies of risk factors for SAH
      published in English from 1966 through March 2005. We calculated pooled relative
      risks (RRs) for longitudinal studies and odds ratios (ORs) for case-control
      studies, both with corresponding 95% CIs. RESULTS: We included 14 longitudinal (5
      new) and 23 (12 new) case-control studies. Overall, the studies included 3936
      patients with SAH (892 cases in 14 longitudinal studies and 3044 cases in 23 case
      control studies) for analysis. Statistically significant risk factors in
      longitudinal and case-control studies were current smoking (RR, 2.2 [1.3 to 3.6];
      OR, 3.1 [2.7 to 3.5]), hypertension (RR, 2.5 [2.0 to 3.1]; OR, 2.6 [2.0 to 3.1]),
      and excessive alcohol intake (RR, 2.1 [1.5 to 2.8]; OR, 1.5 [1.3 to 1.8]).
      Nonwhite ethnicity was a less robust risk factor (RR, 1.8 [0.8 to 4.2]; OR, 3.4
      [1.0 to 11.9]). Oral contraceptives did not affect the risk (RR, 5.4 [0.7 to
      43.5]; OR, 0.8 [0.5 to 1.3]). Risk reductions were found for hormone replacement
      therapy (RR, 0.6 [0.2 to 1.5]; OR, 0.6 [0.4 to 0.8]), hypercholesterolemia (RR,
      0.8 [0.6 to 1.2]; OR, 0.6 [0.4 to 0.9]), and diabetes (RR, 0.3 [0 to 2.2]; OR,
      0.7 [0.5 to 0.8]). Data were inconsistent for lean body mass index (RR, 0.3 [0.2
      to 0.4]; OR, 1.4 [1.0 to 2.0]) and rigorous exercise (RR, 0.5 [0.3 to 1.0]; OR,
      1.2 [1.0 to 1.6]). In the studies included in the review, no other risk factors
      were available for the meta-analysis. CONCLUSIONS: Smoking, hypertension, and
      excessive alcohol remain the most important risk factors for SAH. The seemingly
      protective effects of white ethnicity compared to nonwhite ethnicity, hormone
      replacement therapy, hypercholesterolemia, and diabetes in the etiology of SAH
      are uncertain.

PMID- 16282542
TI  - Plasma adiponectin levels and sonographic phenotypes of subclinical carotid
      artery atherosclerosis: data from the SAPHIR Study.
AB  - BACKGROUND AND PURPOSE: Adipose tissue produces and secretes a number of
      bioactive molecules, conceptualized as adipocytokines. Adiponectin has been
      identified as one of the adipocytokines, and hypoadiponectinemia was demonstrated
      in patients with obesity, diabetes mellitus, and coronary artery disease. Whether
      decreased adiponectin levels are cause or consequence is an important issue in
      the discussion on the association between adiponectin and atherosclerosis. In the
      present study, we investigated the association of plasma adiponectin levels with
      sonographic phenotypes of subclinical atherosclerosis, which may represent
      different stages of disease as well as common and distinct determinants. METHODS:
      A total of 1515 middle-aged healthy white subjects (940 males and 575 females)
      were included. Common carotid artery intima-media thickness (CIMT) and presence
      of atherosclerotic plaques were assessed by B-mode ultrasound. RESULTS: After
      adjustment for established risk factors, per 1 microg/mL decrease in adiponectin
      CIMT increased on the average by 3.48 microm in males (95% CI, 1.23 to 5.73
      microm) and by 2.39 microm in females (95% CI, 0.50 to 4.27 microm). After
      dichotomizing adiponectin levels at the median and adjustment for established
      risk factors, the mean difference of CIMT between subjects with low and high
      adiponectin levels was 20.42 microm in men (95% CI, 6.80 to 34.04; P=0.003) and
      20.75 microm in women (95% CI, 1.08 to 40.42; P=0.039). No significant
      relationship was found between adiponectin levels and presence of atherosclerotic
      plaques. CONCLUSIONS: Our results demonstrate an independent negative association
      of adiponectin levels and CIMT, whereas no relationship with presence of
      atherosclerotic plaques was found, thus suggesting hypoadiponectinemia as a risk
      factor in the development of early atherosclerosis.

PMID- 16282543
TI  - Disparate associations of a functional promoter polymorphism in PCK1 with carotid
      wall ultrasound traits.
AB  - BACKGROUND AND PURPOSE: Cytosolic phosphoenolpyruvate carboxykinase (PEPCK; EC
      4.1.1.32), encoded by PCK1, catalyzes the first committed step in
      gluconeogenesis. We previously showed that a -232C>G promoter polymorphism within
      a cis-acting element required for basal and cAMP-mediated PCK1 gene transcription
      results in loss of negative regulation by insulin, contributing to worsened
      metabolic control in the context of insulin resistance. We hypothesized that this
      polymorphism would be associated with carotid atherosclerosis in a sample of 150
      aboriginal Canadians. METHODS: Dependent variables were 2 distinct carotid
      traits, namely intima-media thickness (IMT) assessed using B-mode ultrasound and
      total carotid plaque volume (TPV) assessed using 3D ultrasound. RESULTS:
      Multivariate analysis showed significant but opposite associations of PCK1
      genotype with these traits. Specifically, subjects with the PCK1-232G/G genotype
      had more carotid IMT (0.80+/-0.02 versus 0.73+/-0.03 mm; P=0.007) but less TPV
      (0.10+/-0.09 versus 0.38+/-0.13; P=0.03) than subjects with other genotypes.
      CONCLUSIONS: The findings connect the key enzyme in gluconeogenesis with
      atherosclerosis. The meaning of the opposing associations of PCK1 genotype with
      IMT and TPV is unclear; more work is required to confirm whether these might be
      distinct quantitative traits with different biological determinants.

PMID- 16282544
TI  - Systemic blood pressure profile in cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy.
AB  - BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) is a genetic form of subcortical
      ischemic vascular dementia (SIVD). The most common vascular risk factors are
      unremarkable in CADASIL; however, studies on systemic blood pressure (BP) changes
      over time are substantially lacking. Because BP instability is a relevant risk
      factor for developing or worsening white matter changes in sporadic SIVD, we
      aimed to study the BP profile of CADASIL to investigate its relationship with
      cognitive decline and white matter injury. METHODS: Twenty-four-hour ambulatory
      BP monitoring was performed in a group of 14 CADASIL patients (12 males and 2
      females) and in a group of 15 healthy age-matched control subjects. The following
      BP variables were compared between the 2 groups: mean daytime and nighttime
      systolic, diastolic, and mean arterial BP (SABPday, DABPday, and MABPday, and
      SABPnight, DABPnight, and MABPnight) and nocturnal percentage decline in arterial
      BP (%MABP reduction). Cognitive performances were tested by mini mental status
      examination (MMSE), and brain MRI was performed to extrapolate the T2-weighted
      lesion volume (LV) in each CADASIL patient. The 24-hour arterial BP variables
      were compared between CADASIL and controls. In addition, for CADASIL patients
      only, MMSE, LV, and age were compared with each pressure variable. RESULTS:
      Patients with CADASIL showed a significant reduction (P<0.05) of SABPday,
      DABPday, MABPday and %MABP decline with respect to controls. In addition, MMSE of
      CADASIL subjects correlated significantly (P<0.0001) with daytime MABP.
      CONCLUSIONS: The low systemic BP profile observed in CADASIL patients was
      specifically attributable to reduced diurnal BP values. This may further affect
      cerebral hemodynamics and increase the risk of cognitive impairment in these
      patients. The pathogenesis of abnormal BP profile in CADASIL remains to be
      clarified. It is likely that central and peripheral mechanisms controlling BP
      variations are involved.

PMID- 16282545
TI  - Trial design in "magnesium sulphate in aneurysmal subarachnoid hemorrhage: a
      randomized controlled trial".

PMID- 16282546
TI  - Neurogenesis in rats after focal cerebral ischemia is enhanced by indomethacin.
AB  - BACKGROUND AND PURPOSE: Newborn cells may participate in repair following
      ischemic brain injury, but their survival and function may be influenced by
      inflammation. METHODS: We investigated the effects of indomethacin, a
      nonsteroidal antiinflammatory drug, on the fate of newborn cells following
      transient focal ischemia. RESULTS: Bromodeoxyuridine (BrdU)-labeled cells,
      including migrating neuroblasts, were observed in the neighboring striatum and
      overlying cortex 1 day poststroke. The density of BrdU+ cells labeled with
      doublecortin, nestin, glial fibrillary acidic protein, or NG2 was increased at 14
      and 28 days. Indomethacin increased BrdU+ cells of all lineages and reduced
      microglial/monocyte activation. CONCLUSIONS: Indomethacin enhanced the
      accumulation of newborn cells following stroke.

PMID- 16282547
TI  - Bone marrow stromal cells that enhanced fibroblast growth factor-2 secretion by
      herpes simplex virus vector improve neurological outcome after transient focal
      cerebral ischemia in rats.
AB  - BACKGROUND AND PURPOSE: Fibroblast growth factor-2 (FGF-2) administration and
      bone marrow stromal cell (MSC) transplantation could improve neurological
      deficits after occlusive cerebrovascular disease. In the present study, we
      examined the effects of neurological improvement after transient middle cerebral
      artery occlusion (MCAO) in rats by a novel therapeutic strategy with FGF-2 gene
      transferred MSCs by the herpes simplex virus type 1 (HSV-1) vector. METHODS:
      Adult Wistar rats were anesthetized. Nonmodified MSCs, FGF-2-modified MSCs with
      HSV-1 1764/-4/pR19/ssIL2-FGF-2, or PBS was administered intracerebrally 24 hours
      after transient right MCAO. All animals underwent behavioral tests for 21 days,
      and the infarction volume with 2-3-5-triphenylterazolium was detected 3 days and
      14 days after the MCAO. Three days and 7 days after the MCAO, the FGF-2
      production in the ipsilateral hemisphere of the MCAO was measured with ELISA.
      Seven and 14 days after the MCAO, immunohistochemical staining for FGF-2 was
      applied. RESULTS: The stroke animals receiving FGF-2-modified MSCs demonstrated
      significant functional recovery compared with the other groups. Fourteen days
      after the MCAO, there was a significant reduction in infarction volume only in
      FGF-2-modified MSC-treated group. FGF-2 production in the FGF-2-modified MSC
      treated brain was significantly higher compared with the other groups at 3 and 7
      days after MCAO. Administrated FGF-2-modified MSCs strongly expressed the FGF-2
      protein, which was proven by ELISA. CONCLUSIONS: Our data suggest that the FGF-2
      gene-modified MSCs with the HSV-1 vector can contribute to remarkable functional
      recovery after stroke compared with MSCs transplantation alone.

PMID- 16282548
TI  - Inhibition of brain GTP cyclohydrolase I and tetrahydrobiopterin attenuates
      cerebral infarction via reducing inducible NO synthase and peroxynitrite in
      ischemic stroke.
AB  - BACKGROUND: Inducible NO synthase (NOS)-derived peroxynitrite (ONOO-) during
      ischemia/reperfusion contributes to ischemic brain injury. However, inducible NOS
      (iNOS) regulation in ischemic stroke remains unknown. Tetrahydrobiopterin (BH4)
      is an essential cofactor for NOS activity. The present study tested the
      hypothesis that inhibition of endogenous BH4 rate-limiting enzyme GTP
      cyclohydrolase I (GTPCH I), and thus BH4 synthesis, reduces cerebral infarction
      via inhibiting iNOS and ONOO- in transient focal ischemia. METHODS: Focal
      ischemia (2 hours) was created in adult male Sprague-Dawley rats (250 to 300 g)
      by middle cerebral artery occlusion (MCAO). Rats were treated 12 hours before
      MCAO with vehicle or diamino-6-hydroxypyrimidine (DAHP; 0.5 g/kg IP), a selective
      GTPCH I inhibitor. Brains were harvested 24 hours after reperfusion for assays of
      infarct volume, blood-brain barrier (BBB) permeability, GTPCH I activity, BH4
      levels, GTPCH I and NOS mRNA, protein expression, and superoxide anion (O2*-) and
      ONOO- levels. RESULTS: Endogenous GTPCH I activity, BH4 levels, iNOS activity,
      and (O2*- and ONOO- levels were all augmented after ischemia/reperfusion. DAHP
      treatment significantly reduced GTPCH I activity, resulting in decreased BH4
      levels, iNOS activity, and ONOO- levels. Consequently, DAHP treatment
      significantly reduced the infarct size compared with the nontreated group (22.3+/
      5.6 versus 38.3+/-7.4%; n=6; P<0.05). Similarly, BBB permeability was
      significantly reduced after DAHP pretreatment compared with the control group
      (4.11+/-0.22 versus 7.78+/-0.44 microg/g tissue; n=5; P<0.05). CONCLUSIONS: These
      results demonstrate that blockade of endogenous brain BH4 synthesis attenuates
      cerebral infarction via inhibiting iNOS and ONOO-, which may provide a
      mechanistic basis of novel therapeutic strategies for ischemic stroke.

PMID- 16282549
TI  - Blood pressure evolution after acute ischemic stroke in patients with and without
      sleep apnea.
AB  - BACKGROUND AND PURPOSE: Sleep apnea (SA) is an independent risk factor for
      arterial hypertension and is present in 50% to 70% of patients with ischemic
      stroke. The effects of SA on blood pressure (BP) and stroke outcome in the acute
      stroke phase are essentially unknown. METHODS: We studied 41 consecutive patients
      admitted within 96 hours after stroke onset. Stroke severity on admission
      (National Institutes of Health Stroke Scale [NIHSS]) and stroke outcome at
      discharge (modified Rankin Disability Scale [mRS]) were assessed. Nocturnal
      breathing was assessed with an ambulatory device the first night after admission.
      SA was defined by an apnea-hypopnea-index (AHI) > or =10/hour, and moderate
      severe SA (MSSA) was defined by an AHI >30/hour. BP monitoring was performed
      during the first 36 hours after admission. A nondipping status (NDS) was defined
      by a ratio >0.9 of mean systolic BP during nights 1 to 2/mean systolic BP during
      day 2. RESULTS: SA was found in 28 (68%) and MSSA in 11 (27%) of 41 patients. A
      correlation was found between AHI and both NIHSS (r=0.331; P=0.035) and mRS
      (r=0.341; P=0.031). Patients with MSSA had higher systolic and diastolic BP
      values during night 1 (P=0.003), day 2 (P=0.004), and night 2 (P=0.03). NDS was
      found in 26 (63%) patients. Nondippers had a similar AHI but higher NIHSS
      (P=0.004) and mRS (P=0.005) than dippers. AHI and NDS were confirmed to be
      independent predictors for both stroke severity and stroke outcome in a multiple
      stepwise linear regression model. CONCLUSIONS: SA severity is associated with
      high 24-hour BP values but only weakly with stroke severity and outcome.
      Conversely, NDS is linked with a more severe stroke and a poorer evolution but
      not with SA severity. These data suggest different, although overlapping,
      pathophysiological and clinical implications of circadian and nocturnal BP values
      in acute stroke.

PMID- 16282551
TI  - Anti-aging medicine: fallacies, realities, imperatives.

PMID- 16282553
TI  - The symmetry of longevity.
AB  - We tested the hypothesis that relatively symmetrical flies live longer. Vein
      measurements on the left and right wings from the same individual were used to
      characterize bilateral symmetry in relationship to age-specific survival in
      defined cohorts. A longitudinal cohort study supported the hypothesis of a
      correlation between bilateral symmetry and longevity. For another type of
      experiment, wings were removed from females and males at approximately the
      beginning of adult life. Thus, there would be no effect of wings per se on adult
      survival. These wings were measured to characterize bilateral asymmetry, and the
      day of death of each dewinged individual was determined. Wing symmetry of females
      and males proved to be a statistically significant predictor of life span,
      especially for males.

PMID- 16282554
TI  - Caloric restriction results in decreased expression of peroxisome proliferator
      activated receptor superfamily in muscle of normal and long-lived growth hormone
      receptor/binding protein knockout mice.
AB  - Resistance to growth hormone, reduced insulin-like growth factor 1 (IGF1) action,
      and enhanced insulin sensitivity are likely mediators of extended life span and
      delayed aging process in growth hormone receptor/binding protein knockout (GHR
      KO) mice. Fat metabolism and genes involved in fatty acid oxidation are strongly
      involved in insulin action. Using real-time polymerase chain reaction and western
      blot we have examined expression of peroxisome proliferator-activated receptors
      (PPARs) and retinoid X receptor (RXR) genes in the skeletal muscle of normal and
      GHR-KO mice subjected to 30% caloric restriction. The results indicate that
      caloric restriction decreased the expression of PPARgamma, PPARalpha, and
      PPARbeta/delta which would lead to down-regulation of fat metabolism. This
      suggested metabolic change clearly does not affect whole-body insulin action.
      These findings suggest that whole-animal insulin sensitivity is not regulated
      through skeletal muscle insulin action.

PMID- 16282555
TI  - Electrophysiological analysis of the effects of ginkgo biloba on visual
      processing in older healthy adults.
AB  - Several studies have tested the efficacy of ginkgo biloba using compromised
      visual systems and have found improvement in vision. We measured functional
      changes in the visual system of older, healthy adults to see if ginkgo extract
      EGb 761 would increase performance in the normal visual system. Two
      electrophysiological measures were taken during baseline, placebo, and treatment
      conditions: visual evoked potentials were used to assess changes in low-level
      functioning of the visual pathways, and P300 recognition responses were measured
      to assess higher order processing. No significant effect was found in the lower
      level visual pathways. However, when using regression analysis across age to
      assess higher order functioning, an improvement was found. The results suggest
      that the higher order processing stages, which may be influenced by cognition,
      decline more rapidly than do lower level processing stages in healthy adults as a
      function of age, and that the use of ginkgo biloba extract may improve the
      functioning of this system.

PMID- 16282556
TI  - Betaine suppresses proinflammatory signaling during aging: the involvement of
      nuclear factor-kappaB via nuclear factor-inducing kinase/IkappaB kinase and
      mitogen-activated protein kinases.
AB  - Betaine is an important human nutrient obtained from various foods. In the
      present study, we assessed the anti-inflammatory effect of betaine on nuclear
      factor-kappaB (NF-kappaB) during aging. Sprague-Dawley (SD) rats, ages 7 and 21
      months, were used in this study. The older rats were fed betaine. To elucidate
      the effect of betaine on oxidative stress-induced NF-kappaB and its signaling
      pathway at molecular levels, YPEN-1 cells were used. Results showed that betaine
      suppressed NF-kappaB and its related gene expressions of cyclooxygenase-2 (COX
      2), inducible nitric oxide synthase (iNOS), vascular cell adhesion molecule-1
      (VCAM-1), and intracellular cell adhesion molecule-1 (ICAM-1) in aged kidney.
      Furthermore, betaine attenuated oxidative stress-induced NF-kappaB via nuclear
      factor-inducing kinase/IkappaB kinase (NIK/IKK) and mitogen-activated protein
      kinases (MAPKs) in the YPEN-1 cells. On the basis of these results, we concluded
      that betaine suppressed the age-related NF-kappaB activities associated with
      upregulated NIK/IKK and MAPKs that were induced by oxidative stress. Thus,
      betaine might be useful as a preventive agent against the activation of NF-kappaB
      induced during inflammation and aging.

PMID- 16282557
TI  - Postprandial hypotension: simple treatment but difficulties with the diagnosis.

PMID- 16282558
TI  - High prevalence of postprandial and orthostatic hypotension among geriatric
      patients admitted to Dutch hospitals.
AB  - BACKGROUND: Previous studies have indicated that postprandial hypotension (PPH)
      and orthostatic hypotension (OH) occur infrequently together. As data on
      geriatric patients in hospitals are scarce, we investigated the prevalence of PPH
      and OH and their combined occurrence. Our study sample included patients admitted
      to two geriatric departments in Dutch hospitals. METHODS: During 9 months,
      hemodynamic changes were measured with Spacelab 90207 after standing and after
      meals in all eligible patients. PPH is defined as a meal-related decline in
      systolic blood pressure (SBP) > or =20 mmHg, OH after standing up. RESULTS:
      Eighty-five patients (44 men), mean age 80 +/- 7 years (range 60-98 years), with
      4 +/- 2 diseases and 6 +/- 3 prescriptions, were included. PPH was present in 57
      patients (67%) with a significant postmeal SBP decrease of 34 +/- 4 mmHg. OH was
      present in 44 patients (52%) with a mean SBP decline of 44 +/- 4 mmHg after
      standing. Thirty-two patients (37%) had OH and PPH. Only 16 patients (19%) had
      neither OH nor PPH. Symptoms of PPH were present in 65% of patients, with syncope
      (in five patients) and sleepiness as the most common symptoms. OH was symptomatic
      in 61% of patients, with dizziness and risk for falls as the most common
      symptoms. CONCLUSIONS: PPH and OH are more common in geriatric patients than was
      previously appreciated, with a high statistical probability that OH and PPH occur
      simultaneously. There is little overlap in symptoms of OH (dizziness, fall risk)
      versus PPH (sleepiness, syncope), which can play an important role in diagnosis.
      Because of the high prevalence of symptomatic PPH and OH, blood pressure
      measurements for diagnosing hypotensive syndromes should be part of a
      comprehensive geriatric assessment.

PMID- 16282559
TI  - Insulin resistance and muscle strength in older persons.
AB  - BACKGROUND: The functional consequences of an age-related insulin resistance (IR)
      state on muscle functioning are unknown. Because insulin is needed for adequate
      muscle function, an age-related insulin-resistant state may also be a determining
      factor. We evaluated the relationship between IR and handgrip muscle strength in
      men and women from a large population-based study (n = 968). METHODS: The degree
      of IR was evaluated by the homeostasis model assessment (HOMA) and muscle
      strength was assessed using handgrip. RESULTS: Simple sex-stratified correlations
      demonstrated that, in men, body mass index-adjusted handgrip strength correlated
      positively with physical activity (r = 0.321; p < .001), muscle area (r = 0.420;
      p < .001), muscle density (r = 0.263; p = .001), plasma albumin (r = 0.156; p =
      .001), insulin-like growth factor-1 (r = 0.258; p < .001), calcium (r = 0.140; p
      = .006), and testosterone (r = 0.325; p < .001) concentrations, whereas a
      negative association was found for age (r = -0.659; p < .001) and myoglobin
      plasma levels (r = -0.164; p =.001). In women, body mass index-adjusted handgrip
      strength correlated positively with physical activity (r = 0.280; p < .001),
      muscle area (r = 0.306; p < .001), muscle density (r = 0.341; p = .001), plasma
      albumin (r = 0.140; p =.001), and insulin-like growth factor-1 (r = 0.300; p <
      .001), whereas a negative association was found for age (r = -0.563; p < .001),
      myoglobin levels (r = -0.164; p = .001), and IR (r = -0.130; p = .04).
      CONCLUSIONS: Sex-stratified analyses adjusted for multiple confounders showed
      that the relationship between IR and handgrip strength was found significant in
      women, whereas it was negligible and not significant in men.

PMID- 16282560
TI  - Insulin resistance as an adverse effect of leuprolide and bicalutamide treatment.

PMID- 16282561
TI  - A critical review of literature regarding the effectiveness of physical therapy
      management of hip fracture in elderly persons.
AB  - The purpose of this review is to analyze the research literature that has
      examined the effectiveness of physical therapy in the management of hip fractures
      in elderly persons. Using literature databases and keywords, we located relevant
      studies. Fifteen studies met the criteria and were then categorized according to
      Sackett's levels of evidence. Six studies were graded at level I, six at level
      II, and three at level V, with level I having the highest level of evidence. From
      the levels of evidence, one grade A, three grade B, and two grade C
      recommendations were developed, with grade A being the most significant
      recommendation. Clinical recommendations are offered about patients with
      dementia, therapeutic exercise, and when and for how long rehabilitation should
      continue. In addition, future research directions are provided.

PMID- 16282562
TI  - Physical function and its response to exercise: associations with cytokine gene
      variation in older adults with knee osteoarthritis.
AB  - BACKGROUND: We determined whether physical function and its response to exercise
      training are associated with polymorphisms in cytokine genes (interleukin-6 [IL
      6] -174 G/C; tumor necrosis factor alpha [TNFalpha] -308 G/A and -238 G/A; and
      TNFalpha receptors [TNFR]1 +36 A/G, TNFR2 +676 T/G, and TNFR2 +1663 A/G), in 214
      older (> or =60 years), overweight (body mass index > or =28 kg/m(2)) individuals
      with knee osteoarthritis. METHODS: Physical function (walking distance, stair
      climb time, self-reported disability) was measured before and after an 18-month
      randomized, controlled exercise trial involving walking and weight lifting 3
      days/week. RESULTS: In cross-sectional analyses, baseline walking distance was
      greater in individuals homozygous for the major G allele at IL-6 -174 compared to
      individuals with at least one C allele (p = .05). Both walking distance (p =.02)
      and stair-climb time (p = .003) were better in individuals homozygous for the
      major G allele of the TNFalpha -308 polymorphism compared to those with at least
      one A allele. Walking distance was better (p = .02), and stair-climb time tended
      to be better (p = .06), in individuals homozygous for the major T allele of the
      TNFR2 +676 polymorphism. No associations were seen with self-reported physical
      disability nor with the other polymorphisms. In response to exercise, there was a
      significant interaction between TNFalpha -308 genotype and exercise treatment on
      6-month changes in stair-climb time (p = .007), and on 18-month changes in self
      reported physical disability (p = .01), such that individuals with an A allele
      showed greater improvement in response to exercise. CONCLUSIONS: Walking distance
      and stair climbing speed are partly influenced by genetic variation in the IL-6
      and TNFalpha genes in older individuals with knee osteoarthritis.

PMID- 16282563
TI  - Contribution of genetic and environmental factors to individual differences in
      maximal walking speed with and without second task in older women.
AB  - BACKGROUND: Among older people, distraction while walking may increase the risk
      of falls. Factors underlying individual differences in dual tasking are not fully
      understood. Our aim was to study the effect of a second task on maximal walking
      speed and to examine whether individual differences in walking speed measured
      with and without a second task are accounted for by genetic and environmental
      influences shared across tasks or specific to each task. METHODS: The data were
      collected from the 101 monozygotic and 116 dizygotic twin pairs aged 63-76 years
      recruited from the Finnish Twin Cohort. Maximal walking speed (MWS) over 10 m was
      measured on a laboratory corridor and timed with photocells. The test was
      repeated while subjects performed, first, a manual task (MWSmanual) and, second,
      a verbal task (MWSverbal). RESULTS: Mean walking speed without a simultaneous
      task was 1.72 m/s (standard deviation [SD] 0.33), with a manual task it was 1.52
      m/s (SD 0.26), and with a verbal task it was 1.36 m/s (SD 0.27). Multivariate
      genetic analysis showed that an additive genetic factor in common accounted for
      17% of individual differences in MWS, 19% in MWSmanual, and 12% in MWSverbal. In
      addition, MWSverbal had a genetic factor specific to it accounting for 10% of the
      variance. Shared environmental influences, common to all three traits, accounted
      for 39%, 27%, and 21% of the individual differences, respectively. CONCLUSION:
      Approximately half of the individual differences in walking with or without
      another task were accounted for by genetic and nongenetic familial effects in
      common, and the rest of the variation was accounted for by unique environmental
      factors in common and factors specific to walking tests.

PMID- 16282564
TI  - Gait velocity as a single predictor of adverse events in healthy seniors aged 75
      years and older.
AB  - PURPOSE: Although gait velocity (GV) measurement could predict poor outcomes, few
      studies regarding its usefulness as a single test in well functioning elderly
      persons have been pursued. The aim of this study was to asses whether GV could be
      sufficient to predict adverse events such as hospitalization for any cause,
      requirement for a caregiver, nursing home placement, falls, fractures, or death
      in healthy elderly persons. METHODS: Ours was a cohort study comprising 102 well
      functioning participants aged 75 and older. Demographic features, health status,
      and functional capacity were assessed at baseline and followed for adverse
      outcomes. Measurements included evaluation of cognition, activities of daily
      living, and mobility. The time required to walk the middle 8 meters of 10 meters
      was defined as GV. Three GV groups were distinguished: high GV (>1.1 m/s), median
      GV (1-0.7 m/s), and low GV (<0.7 m/s). RESULTS: At baseline, the three groups
      were comparable in their health status with an average age of 79.6 +/- 4 years.
      At 24 months, the low GV group had a significantly higher incidence of adverse
      events than did the other groups. Low GV was a predictor of hospitalization
      (relative risk [RR] = 5.9, 95% confidence interval [CI], 1.9-8.5), requirement of
      a caregiver (RR = 9.5, 95% CI, 1.3-2.5), and new falls (RR = 5.4, 95% CI, 2.0
      4.3). These associations remained significant after a multiple logistic
      regression analysis. CONCLUSIONS: GV measurement in the ambulatory setting may
      allow the detection of healthy elderly people at risk for adverse events. These
      data may suggest that simple assessment of GV is enough to predict adverse events
      in well functioning older persons.

PMID- 16282565
TI  - Trunk repositioning errors are increased in balance-impaired older adults.
AB  - BACKGROUND: Controlling the flexing trunk is critical in recovering from a loss
      of balance and avoiding a fall. To investigate the relationship between trunk
      control and balance in older adults, we measured trunk repositioning accuracy in
      young and balance-impaired and unimpaired older adults. METHODS: Young adults (N
      = 8, mean age 24.3 years) and two groups of community-dwelling older adults
      defined by unipedal stance time (UST)-a balance-unimpaired group (UST > 30
      seconds, N = 7, mean age 73.9 years) and a balance-impaired group (UST < 5
      seconds, N = 8, mean age 79.6 years)-were tested in standing trunk control
      ability by reproducing a approximately 30 degrees trunk flexion angle under three
      visual-surface conditions: eyes opened and closed on the floor, and eyes opened
      on foam. Errors in reproducing the angle were defined as trunk repositioning
      errors (TREs). Clinical measures related to balance, trunk extensor strength, and
      self-reported disability were obtained. RESULTS: TREs were significantly greater
      in the balance-impaired group than in the other groups, even when controlling for
      trunk extensor strength and body mass. In older adults, there were significant
      correlations between TREs and three clinical measures of balance and fall risk,
      UST and maximum step length (-0.65 to -0.75), and Timed Up & Go score (0.55), and
      between TREs and age (0.63-0.76). In each group TREs were similar under the three
      visual-surface conditions. Test-retest reliability for TREs was good to excellent
      (intraclass correlation coefficients > or =0.74). CONCLUSIONS: Older balance
      impaired adults have larger TREs, and thus poorer trunk control, than do balance
      unimpaired older individuals. TREs are reliable and valid measures of underlying
      balance impairment in older adults, and may eventually prove to be useful in
      predicting the ability to recover from losses of balance and to avoid falls.

PMID- 16282566
TI  - Chronic resistance exercise training improves natural killer cell activity in
      older women.
AB  - BACKGROUND: Regular exercise has been reported to slow the age-associated
      declines in natural killer cell activity (NKCA). To evaluate this response, we
      recruited older, postmenopausal women (65-85 years old) to fill one of two
      groups: training (10 weeks of resistance exercise; TR) or control. METHODS: Blood
      samples were collected from an arm vein in the TR group at rest (PRE),
      immediately following (POST), and 2 hours (2H) following an acute bout of
      resistance exercise both before (BEFORE) and after (AFTER) training. Leukocytes
      and NKCA were determined by flow cytometry and a whole blood (51)Cr release
      assay, respectively. RESULTS: Acute exercise increased total leukocyte (p < .05),
      CD8 (p < .05), CD4 (p < .05), and CD56 counts (p < .05), but there was no effect
      of training. NKCA was greater TR-AFTER-PRE (136%), -POST (80%), and -2H (127%)
      compared to similar values from TR-BEFORE (p < .05). CONCLUSION: Increased
      resting NKCA after chronic resistance training suggests that immunity has been
      improved.

PMID- 16282567
TI  - The apolipoprotein E e4 polymorphism is strongly associated with poor mobility
      performance test results but not self-reported limitation in older people.
AB  - BACKGROUND: The apolipoprotein E (ApoE) e4 polymorphism is linked to increased
      mortality rates, Alzheimer's disease, and cardiovascular disease in older people,
      but previous studies have largely failed to detect an effect on self-reported
      mobility disability. We hypothesized that poor performance on mobility-related
      tests may provide a better measure of effects, and we aimed to estimate the
      extent to which the ApoE e4 allele increases risks of poor performance on
      measured mobility and self-reported mobility disability compared to e3/3, in a
      medium-sized population cohort. METHODS: Data were from 1262 people at baseline
      older than 65 years from the Longitudinal Aging Study Amsterdam (LASA), followed
      up for 6 years. Age- and sex-adjusted logistic regression models were used to
      explore associations. RESULTS: At baseline, those individuals with an e4 allele
      had an odds ratio of 2.26 (95% confidence interval, 1.31-3.90) for poor
      performance on gait speed testing (<0.4 m/s) and 1.94 (95% confidence interval,
      1.19-3.16) for five chair stands (> or =20 s), compared to those with e3/3
      status. At follow-up, associations between e4 status and incident poor
      performance on the chair stand test was significant. Associations with self
      reported inability or need for help walking for 5 minutes or for climbing 15
      steps were nonsignificant throughout. CONCLUSIONS: The ApoE e4 polymorphism is
      associated with a substantial excess of mobility limitation. The impact is
      detectable by performance testing, but not by self-reports. Poor results on
      mobility performance tests may provide a phenotype of ageing.

PMID- 16282568
TI  - Acute phase response detection and quantitation at the point of care in older
      adults with acute bacterial infections.
AB  - BACKGROUND: We investigated the reliability of a slide test in determining the
      presence of acute bacterial infections in a group of older adults to determine
      the usefulness of this test at the point of care. METHODS: The study group
      included older adults with an acute bacterial infection and matched controls. We
      examined the white blood cell count (WBCC), the erythrocyte sedimentation,
      fibrinogen concentration, and high sensitivity C-reactive protein (hs-CRP), in
      addition to the slide test that reveals the number of leukocytes and degree of
      erythrocyte aggregation. RESULTS: There were 144 patients and 144 controls at a
      respective mean +/- standard deviation age of 71.3 +/- 20.7 and 70.6 +/- 20.2
      years. A highly significant difference was noted between patients and controls in
      all laboratory markers, both conventional and those obtained by the slide test.
      By using hs-CRP, we correctly predicted the individual group as control or
      bacterial infection. When analyzed by means of a receiver-operated characteristic
      (ROC) curve, hs-CRP was again most reliable, with the slide leukocyte test being
      superior to the WBCC. CONCLUSION: The slide leukocyte count provided a similar
      diagnostic yield to that of the WBCC. The availability of this slide test at the
      point of care will provide the clinician with a useful biomarker when faced with
      clinical decisions in the care of older adults.

PMID- 16282569
TI  - Cerebrovascular diseases as primary hospital discharge diagnoses: national trend
      (1970-2000) among older adults.
AB  - BACKGROUND: Cerebrovascular diseases are a common cause of mortality, morbidity,
      and hospitalization among older adults. However, the long-term national trends in
      cerebrovascular disease-related hospitalizations in this age group are not well
      known. METHODS: We used the National Center for Health Statistics trend data from
      the National Hospital Discharge Surveys (1970-2000) to determine incidence of
      cerebrovascular disease-related hospitalizations among persons 65 years and older
      in the United States. Only patients discharged with a primary discharge diagnosis
      of cerebrovascular disease were included. We estimated rates of hospitalization
      per 1000 civilian residents 65 years and older, for all patients and stratified
      by age, sex, and race. RESULTS: Among persons 65 years of age and older, the
      total number of cerebrovascular disease-related hospitalizations increased from
      372,000 in 1970 to 711,000 in 2000. However, the rates of hospitalization due to
      cerebrovascular disease remained unchanged at 20.7/1000 in 1970 and 20.4/1000 in
      2000. The rates for persons 75-84 years and >85 years were, respectively, 2 and 3
      times higher than that for persons 65-74 years throughout the study period. Rates
      for men and women were comparable and stable during the study period. Rates for
      African Americans, in contrast, increased from 14/1000 in 1970 to 20.6/1000 in
      2000, peaking in 1985 (27.4/1000). CONCLUSIONS: The overall rates of
      hospitalization due to cerebrovascular disease remained high yet stable. However,
      the absolute number of hospitalizations due to cerebrovascular disease increased
      considerably, with potential for serious social, financial, and public health
      implications for the coming decades.

PMID- 16282570
TI  - Long-term prediction of mortality in elderly persons by dobutamine stress
      echocardiography.
AB  - BACKGROUND: Dobutamine stress echocardiography (DSE) was shown to provide
      incremental prognostic information. However, its role in the prediction of
      mortality in elderly persons is not well defined. We assessed the value of DSE in
      the prediction of mortality and hard cardiac events during long-term follow-up in
      patients older than 65 years. METHODS: We studied 1434 patients >65 years old
      (mean age 72 +/- 3 years) who underwent DSE for evaluation of coronary artery
      disease. Ischemia was defined as new or worsening wall motion abnormalities.
      Follow-up events were total mortality and hard cardiac events (cardiac mortality
      and nonfatal myocardial infarction). Multivariable Cox regression analysis was
      used to identify the independent predictors of follow-up events. RESULTS:
      Ischemia was detected in 675 patients (47%). Five hundred six patients (35%) had
      a normal study, and 253 (18%) had fixed wall motion abnormalities. During a mean
      follow-up of 6.5 years, 532 (37%) deaths occurred, of which 249 (17%) were due to
      cardiac causes. A nonfatal myocardial infarction occurred in 45 patients (3%).
      Independent predictors of all-cause mortality in a multivariate analysis model
      were age (hazard ratio [HR] 1.06; 95% confidence interval [CI], 1.05-1.08), male
      sex (HR 1.5; 95% CI, 1.2-1.8), hypertension (HR 1.2; 95% CI, 1.1-1.4), smoking
      (HR 1.3; 95% CI, 1.1-1.6), diabetes (HR 1.4; 95% CI, 1.1-1.8), rest wall motion
      abnormalities (HR 1.07; 95% CI, 1.06-1.09), and ischemia (HR 1.3; 95% CI, 1.1
      1.6). Independent predictors of hard cardiac events were age (HR 1.07; 95% CI,
      1.05-1.09), male sex (HR 1.3; 95% CI, 1.1-1.7), smoking (HR 1.3; 95% CI, 1.1
      1.6), diabetes (HR 1.6; 95% CI, 1.2-2.2), rest wall motion abnormalities (HR
      1.13; 95% CI, 1.12-1.16), and ischemia (HR 2.1; 95% CI, 1.5-2.8). CONCLUSION: DSE
      provides independent prognostic information to predict all-cause mortality and
      hard cardiac events in elderly patients.

PMID- 16282572
TI  - The future (history) of socioeconomic measurement and implications for improving
      health outcomes among African Americans.
AB  - Socioeconomic status (SES) has powerful and complex impacts on health, and
      understanding the relationship between SES and health is essential for long-term
      improvements in the health of populations. In addition, in the United States, the
      impact of SES on health is inextricably intertwined with racial and ethnicity
      status and the historical development and maintenance of health disparities. Most
      of the literature documenting this relationship has focused on individual-level
      socioeconomic factors. There are sound theoretical reasons and some empirical
      support to suggest that socioeconomic resources at both individual and
      neighborhood levels have strong influences on health outcomes such as disease,
      disability, and mortality. However, these relationships have been inadequately
      examined to date. In this article, the term "ecological SES" will be used to
      denote SES at geographic group levels. As the United States attempts to achieve
      the goals of the Department of Health and Human Services' Healthy People 2010
      program, understanding ecological SES and its impacts on health will be crucial.
      We review the theory, some of the empirical evidence, and likely future for the
      measurement and use of a broader approach to SES and offer a specific research
      paradigm for examining these issues. We focus in particular on one racial-ethnic
      group that experiences health disparity, that is, African Americans. We use our
      ongoing project investigating physical frailty in urban African Americans to
      illustrate the importance of a multilevel approach to understanding the impacts
      of socioeconomic resources on health and the potential implications for efforts
      to prevent or reverse frailty.

PMID- 16282571
TI  - Association of diastolic dysfunction and outcomes in ambulatory older adults with
      chronic heart failure.
AB  - BACKGROUND: Studies of patients with heart failure and preserved systolic
      function report variable outcomes compared with those of patients with impaired
      systolic function. OBJECTIVE: To study outcomes of diastolic (vs systolic) heart
      failure in older adults with chronic heart failure. METHODS: Patients were
      ambulatory chronic heart failure patients 65 years and older (N = 3984) who
      participated in the Digitalis Investigation Group trial. Of these, 3405 had
      systolic heart failure (ejection fraction < or =45%) and 579 had diastolic heart
      failure (ejection fraction >45%). By using a 1:1 match by age, sex, and race, 571
      diastolic heart failure patients were matched with 571 systolic heart failure
      patients. Kaplan-Meier survival analyses and multivariable Cox proportional
      hazard analyses were used to estimate the risk of various outcomes between the
      groups. RESULTS: During the 1044 mean days of follow up, compared with 41% of
      systolic heart failure patients, 27% of diastolic heart failure patients died (p
      <.001). Presence of diastolic heart failure was independently associated with a
      27% decreased risk of all-cause death (adjusted hazard ratio [HR] = 0.73; 95%
      confidence interval [CI], 0.58-0.91) and a 32% reduction in risk of
      hospitalization due to heart failure (adjusted HR = 0.68; 95% CI, 0.52-0.88).
      There was no difference in overall hospitalization between the groups. However,
      compared with systolic heart failure patients, diastolic heart failure patients
      were more likely to be hospitalized due to noncardiovascular causes (adjusted HR
      = 1.38; 95% CI, 1.02-1.88). CONCLUSIONS: Older adults with diastolic heart
      failure had lower risk of all-cause mortality and heart failure-related
      hospitalizations, but higher risk of noncardiovascular hospitalization.

PMID- 16282573
TI  - Health changes among Swedish oldest old: prevalence rates from 1992 and 2002 show
      increasing health problems.
AB  - BACKGROUND: The health of the elderly population is of utmost importance for
      planning policy and resources for care services. Most surveys of the health of
      the elderly population show improvement, suggesting support for the compression
      of morbidity hypothesis. This study examines changes in the health of the Swedish
      population (aged 77+) from 1992 to 2002. METHODS: Two nationally representative
      surveys of the elderly population (n = 537 and 563, respectively), including both
      community-based and institutionalized persons were used. Outcomes include self
      reported diseases, symptoms, and activities of daily living, as well as objective
      tests of physical capacity, lung function, vision, and cognition. RESULTS: None
      of the indicators showed improvement. A number of health indicators showed
      significant worsening, with or without adjustment for changes in the age and sex
      distribution from 1992 to 2002. Among self-reported indicators, there were
      significant increases in several diseases and symptoms. The objective function
      tests also showed significantly worse results in 2002 compared to 1992 for
      physical capacity, lung function, and cognition. No significant differences in
      activities of daily living limitations were found. CONCLUSIONS: In light of
      several recent studies, we expected to observe improvements in the health of the
      elderly population. However, this study showed no signs of improvement. On the
      contrary, we found a pattern of worsening health. The study included objective
      tests of function, implying that results are not due solely to raised
      expectations or changes in reporting. Possible explanations are discussed.

PMID- 16282574
TI  - Effects of knee flexion angles for graft fixation on force distribution in double
      bundle anterior cruciate ligament grafts.
AB  - BACKGROUND: In double-bundle anterior cruciate ligament reconstruction,
      overloading either 1 of the 2 grafts should be avoided to decrease the risk of
      graft failure. HYPOTHESIS: Overloading of the posterolateral graft may occur when
      it is fixed at 30 degrees of knee flexion because the posterolateral bundle is
      elongated as the knee approaches extension. STUDY DESIGN: Controlled laboratory
      study. METHODS: Ten human cadaveric knees were tested at (1) intact, (2) anterior
      cruciate ligament-deficient, (3) double-bundle anterior cruciate ligament
      reconstruction with the anteromedial and posterolateral grafts fixed at 60
      degrees of flexion and full extension, respectively (fixation 60/FE), and (4)
      double-bundle anterior cruciate ligament reconstruction with both grafts fixed at
      30 degrees of flexion simultaneously (fixation 30/30). Two external loading
      conditions simulating clinical examinations were used: (1) 134-N anterior tibial
      load and (2) combined rotatory loads of 10 N x m valgus and 5 N x m internal
      tibial torques. Data on knee kinematics and in situ forces in the 2 bundles of
      the intact anterior cruciate ligament and the respective grafts were obtained.
      RESULTS: In response to 134-N anterior tibial load, knee kinematics and in situ
      force in the grafts were similar to the intact knee for both fixation protocols.
      The force in the anteromedial graft for fixation 60/FE was 34% higher, whereas
      the posterolateral graft for fixation 30/30 was 46% higher, compared with the
      intact anteromedial and posterolateral bundles, respectively. In response to
      combined rotatory loads, the posterolateral graft for fixation 30/30 carried 67%
      higher load than did the intact posterolateral bundle. CONCLUSION: Fixation 30/30
      overloaded the posterolateral graft, whereas fixation 60/FE overloaded the
      anteromedial graft. CLINICAL RELEVANCE: In double-bundle anterior cruciate
      ligament reconstruction, even though overall forces in the graft are the same as
      intact anterior cruciate ligament, the force distributions may not be the same as
      the intact bundles, and overloading of 1 of the 2 grafts may occur.

PMID- 16282575
TI  - Scapular kinematics during supraspinatus rehabilitation exercise: a comparison of
      full-can versus empty-can techniques.
AB  - BACKGROUND: Supraspinatus strengthening is an important component of shoulder
      rehabilitation. Previous work has determined that the full-can and empty-can
      exercises elicit the greatest amount of supraspinatus activity. However, scapular
      kinematics has not been considered when prescribing supraspinatus exercises.
      HYPOTHESIS: Scapular downward rotation, internal rotation, and anterior tipping
      during the empty-can exercise are increased when compared with the full-can
      exercise. STUDY DESIGN: Descriptive laboratory study. METHODS: Twenty
      participants performed full-can and empty-can exercises while an electromagnetic
      tracking system was used to collect three-dimensional scapular kinematic data.
      Scapular angles at 30 degrees, 60 degrees, and 90 degrees of the ascending and
      descending phases of humeral elevation were compared using 2-way repeated
      measures analysis of variance. RESULTS: There was more scapular anterior tipping
      and internal rotation during the empty-can exercise at all sampled humeral
      elevation angles except at 30 degrees of the descending phase for
      anterior/posterior tipping (P < .05). CONCLUSION: Scapular anterior tipping and
      internal rotation are increased during the empty-can exercise, whereas scapular
      upward rotation was not different between exercises. CLINICAL RELEVANCE:
      Increased scapular internal rotation and anterior tipping decrease the volume of
      the supraspinatus outlet during the empty-can exercise. When maintenance of the
      subacromial space is important, use of the full-can exercise seems most
      appropriate for selective strengthening of the supraspinatus muscle.

PMID- 16282576
TI  - Kinematics and kinetics of elite windmill softball pitching.
AB  - BACKGROUND: A significant number of time-loss injuries to the upper extremity in
      elite windmill softball pitchers has been documented. The number of outings and
      pitches thrown in 1 week for a softball pitcher is typically far in excess of
      those seen in baseball pitchers. Shoulder stress in professional baseball
      pitching has been reported to be high and has been linked to pitching injuries.
      Shoulder distraction has not been studied in an elite softball pitching
      population. HYPOTHESIS: The stresses on the throwing shoulder of elite windmill
      pitchers are similar to those found for professional baseball pitchers. STUDY
      DESIGN: Descriptive laboratory study. METHODS: Three-dimensional, high-speed (120
      Hz) video data were collected on rise balls from 24 elite softball pitchers
      during the 1996 Olympic Games. Kinematic parameters related to pitching mechanics
      and resultant kinetics on the throwing shoulder were calculated. Multiple linear
      regression analysis was used to relate shoulder stress and pitching mechanics.
      RESULTS: Shoulder distraction stress averaged 80% of body weight for the Olympic
      pitchers. Sixty-nine percent of the variability in shoulder distraction can be
      explained by a combination of 7 parameters related to pitching mechanics.
      CONCLUSION: Excessive distraction stress at the throwing shoulder is similar to
      that found in baseball pitchers, which suggests that windmill softball pitchers
      are at risk for overuse injuries. Normative information regarding upper extremity
      kinematics and kinetics for elite softball pitchers has been established.

PMID- 16282577
TI  - A biomechanical evaluation of an anatomical coracoclavicular ligament
      reconstruction.
AB  - BACKGROUND: Despite numerous surgical techniques described, there have been few
      studies evaluating the biomechanical performance of acromioclavicular joint
      reconstructions. PURPOSE: To compare a newly developed anatomical
      coracoclavicular ligament reconstruction with a modified Weaver-Dunn procedure
      and a recently described arthroscopic method using ultrastrong nonabsorbable
      suture material. STUDY DESIGN: Controlled laboratory study. METHODS: Forty-two
      fresh-frozen cadaveric shoulders (72.8 +/- 13.4 years) were randomly assigned to
      3 groups: arthroscopic reconstruction, anatomical coracoclavicular
      reconstruction, and a modified Weaver-Dunn procedure. Bone mineral density was
      obtained on all specimens. Specimens were tested to 70 N in 3 directions,
      anterior, posterior, and superior, comparing the intact to the reconstructed
      states. Superior cyclic loading at 70 N for 3000 cycles was then performed at a
      rate of 1 Hz, followed by a load to failure test (120 mm/min) to simulate
      physiologic states at the acromioclavicular joint. RESULTS: In comparison to the
      intact state, the modified Weaver-Dunn procedure had significantly (P < .05)
      greater laxity than the anatomical coracoclavicular reconstruction or the
      arthroscopic reconstruction. There were no significant differences in bone
      mineral density (g/cm(2)), load to failure, superior migration over 3000 cycles,
      or superior displacement. The anatomical coracoclavicular reconstruction had
      significantly less (P < .05) anterior and posterior translation than the modified
      Weaver-Dunn procedure. The arthroscopic reconstruction yielded significantly less
      anterior displacement (P < .05) than the modified Weaver-Dunn procedure.
      CONCLUSION: The anatomical coracoclavicular reconstruction has less anterior and
      posterior translation and more closely approximates the intact state, restoring
      function of the acromioclavicular and coracoclavicular ligaments. CLINICAL
      RELEVANCE: A more anatomical reconstruction using a free tendon graft of both the
      trapezoid and conoid ligaments may provide a stronger, permanent biologic
      solution for dislocation of the acromioclavicular joint. This reconstruction may
      minimize recurrent subluxation and residual pain and permit earlier
      rehabilitation.

PMID- 16282578
TI  - Jump-land characteristics and muscle strength development in young athletes: a
      gender comparison of 1140 athletes 9 to 17 years of age.
AB  - BACKGROUND: Many authors have speculated that altered neuromuscular control and
      strength of the lower extremity are responsible for the gender disparity in knee
      ligament injury rates. HYPOTHESIS: Significant increases in normalized quadriceps
      and hamstrings strength and limb symmetry on single-legged hop test occur with
      age. No gender differences in strength occur until age 14 years, after which boys
      generate greater peak torques than do girls. Age and gender do not influence
      lower limb alignment on a drop-jump test. STUDY DESIGN: Cross-sectional study;
      Level of evidence, 3. METHODS: We studied the effects of age and gender in 1140
      athletes, 9 to 17 years old, on muscle strength and neuromuscular control during
      functional activities. Isokinetic quadriceps and hamstrings strength was measured
      at 300 deg/s. Limb symmetry was assessed with single-legged hop tests. A video
      drop-jump test determined lower limb alignment in the coronal plane. RESULTS:
      Extension peak torques significantly increased with age; maximum strength was
      noted in girls at age 13 years and in boys at age 14 years (P < .001). Although
      maximum flexion strength occurred in boys at age 14 years (P < .001), girls had
      only slight increases from ages 9 to 11 years (P = not significant). Boys aged 14
      to 17 years had significantly greater normalized isokinetic strength than did age
      matched girls. No age or gender effects existed in limb alignment on the drop
      jump test or limb symmetry on single-legged hop testing. CONCLUSION: Maximum
      hamstrings strength was noted in female athletes by age 11 years, compared with
      age 14 years in male athletes, and a distinct lower limb valgus alignment existed
      in the majority of all athletes on landing. The absence of a gender difference in
      lower limb alignment on landing suggests other factors may be responsible for the
      gender disparity in knee ligament injury rates.

PMID- 16282579
TI  - The effects of plyometric versus dynamic stabilization and balance training on
      lower extremity biomechanics.
AB  - BACKGROUND: Neuromuscular training that includes both plyometric and dynamic
      stabilization/balance exercises alters movement biomechanics and reduces ACL
      injury risk in female athletes. The biomechanical effects of plyometric and
      balance training utilized separately are unknown. HYPOTHESIS: A protocol that
      includes balance training without plyometric training will decrease coronal plane
      hip, knee, and ankle motions during landing, and plyometric training will not
      affect coronal plane measures. The corollary hypothesis was that plyometric and
      balance training effects on knee flexion are dependent on the movement task
      tested. STUDY DESIGN: Controlled laboratory study. METHODS: Eighteen high school
      female athletes participated in 18 training sessions during a 7-week period. The
      plyometric group (n = 8) performed maximum-effort jumping and cutting exercises,
      and the balance group (n = 10) used dynamic stabilization/ balance exercises
      during training. Lower extremity kinematics were measured during the drop
      vertical jump and the medial drop landing before and after training using 3D
      motion analysis techniques. RESULTS: During the drop vertical jump, both
      plyometric and balance training reduced initial contact (P = .002), maximum hip
      adduction angle (P = .015), and maximum ankle eversion angle (P = .020). During
      the medial drop landing, both groups decreased initial contact (P = .002) and
      maximum knee abduction angle (P = .038). Plyometric training increased initial
      contact knee flexion (P = .047) and maximum knee flexion (P = .031) during the
      drop vertical jump, whereas the balance training increased maximum knee flexion
      (P = .005) during the medial drop landing. CONCLUSION: Both plyometric and
      balance training can reduce lower extremity valgus measures. Plyometric training
      affects sagittal plane kinematics primarily during a drop vertical jump, whereas
      balance training affects sagittal plane kinematics during single-legged drop
      landing. CLINICAL RELEVANCE: Both plyometric and dynamic stabilization/balance
      exercises should be included in injury-prevention protocols.

PMID- 16282580
TI  - Operative treatment of ulnar collateral ligament insufficiency of the elbow in
      female athletes.
AB  - BACKGROUND: As women become more involved in athletic activity, injuries specific
      to this population also increase. No data exist regarding operative treatment of
      female patients with elbow instability secondary to ulnar collateral ligament
      insufficiency. HYPOTHESIS: Women with symptomatically unstable elbows who failed
      nonoperative treatment will improve after surgical intervention. STUDY DESIGN:
      Case series; Level of evidence, 4. METHODS: Nineteen women were retrospectively
      evaluated using the Andrews and Carson Elbow Outcome Score. Patients were
      included if they underwent repair or reconstruction of the ulnar collateral
      ligament for symptomatic instability that precluded them from participation in
      their desired sport or activities, despite nonoperative treatment. RESULTS: The
      mean age was 22.0 years (range, 15.1-37.2 years). The mean follow-up was 38.8
      months (range, 12.4-68.6 months). Of the 19 patients, 14 were softball players,
      gymnasts, and tennis players. Only 1 was a pitcher. Eighteen women underwent
      repair by one of the following procedures: plication (n = 6), repair to bone
      using anchors (n = 11), or drill holes (n = 1). One patient underwent a palmaris
      graft reconstruction. The mean overall preoperative outcome score of 120 improved
      to 191 postoperatively (P < .0001). Seventeen of 18 athletes were able to return
      to their sport at a mean of 2.5 months postoperatively. One patient did not
      participate in athletics. CONCLUSION: This study demonstrated excellent overall
      results in 16 and good results in 3 female patients after medial elbow repair or
      reconstruction. Women appear to be able to consistently return to a high level of
      function after repair or reconstruction for medial elbow instability.

PMID- 16282581
TI  - Biomechanical comparison of a single-row versus double-row suture anchor
      technique for rotator cuff repair.
AB  - BACKGROUND: Reestablishment of the native footprint during rotator cuff repair
      has been suggested as an important criterion for optimizing healing potential and
      fixation strength. HYPOTHESIS: A double-row rotator cuff footprint repair will
      demonstrate superior biomechanical properties compared with a single-row repair.
      STUDY DESIGN: Controlled laboratory study. METHODS: In 9 matched pairs of fresh
      frozen cadaveric shoulders, the supraspinatus tendon from 1 shoulder was repaired
      with a double-row suture anchor technique: 2 medial anchors with horizontal
      mattress sutures and 2 lateral anchors with simple sutures. The tendon from the
      contralateral shoulder was repaired using a single lateral row of 2 anchors with
      simple sutures. Each specimen underwent cyclic loading from 10 to 180 N for 200
      cycles, followed by tensile testing to failure. Gap formation and strain over the
      footprint area were measured using a video digitizing system; stiffness and
      failure load were determined from testing machine data. RESULTS: Gap formation
      for the double-row repair was significantly smaller (P < .05) when compared with
      the single-row repair for the first cycle (1.67 +/- 0.75 mm vs 3.10 +/- 1.67 mm,
      respectively) and the last cycle (3.58 +/- 2.59 mm vs 7.64 +/- 3.74 mm,
      respectively). The initial strain over the footprint area for the double-row
      repair was nearly one third (P < .05) the strain of the single-row repair. Adding
      a medial row of anchors increased the stiffness of the repair by 46% and the
      ultimate failure load by 48% (P < .05). CONCLUSION: Footprint reconstruction of
      the rotator cuff using a double-row repair improved initial strength and
      stiffness and decreased gap formation and strain over the footprint when compared
      with a single-row repair. CLINICAL RELEVANCE: To achieve maximal initial fixation
      strength and minimal gap formation for rotator cuff repair, reconstructing the
      footprint attachment with 2 rows of suture anchors should be considered.

PMID- 16282582
TI  - The effect of angled osteochondral grafting on contact pressure: a biomechanical
      study.
AB  - BACKGROUND: Flush osteochondral plugs can reduce contact pressure compared with
      an empty defect in the articular cartilage. However, incongruities such as graft
      angulation have an unknown effect. HYPOTHESIS: Incongruity of the articular
      cartilage after osteochondral transplantation affects articular surface contact
      pressure. STUDY DESIGN: Controlled laboratory study. METHODS: An 80-N load was
      applied with a material testing system for 120 seconds to the femoral condyles of
      50 fresh swine knees. Contact pressures were measured using Prescale super low
      film. Five conditions were tested: (1) intact articular surface; (2) surface with
      4.5-mm-diameter circular defect; (3) defect grafted with a flush 4.5-mm-diameter
      plug from the contralateral condyle; (4) defect grafted with a 30 degrees angled
      4.5-mm-diameter plug, with lower edge flush (tip elevated with respect to the
      adjacent surface); and (5) defect grafted with a 30 degrees plug, with tip flush
      to the adjacent surface (lower edge sunk). Angled grafts were obtained using a
      rotational bearing vise aligned with a 30 degrees fixed-angle track. The film was
      digitally scanned and analyzed, and standard statistical tests were performed.
      RESULTS: Mean peak pressures of intact cartilage (8.57 kg/cm2), flush graft (9.81
      kg/cm2), and sunk and angled graft (9.15 kg/cm2) were not significantly different
      (P < .5). The mean pressures for defects (12.01 kg/cm2) and the elevated angled
      graft (14.50 kg/cm2) were significantly (P < .05) higher than that of intact
      cartilage. CLINICAL RELEVANCE: Slightly sunk grafts were still able to reduce
      elevated contact pressures to normal levels. However, elevated angled grafts
      increased contact pressure. These results suggest that it is preferable to leave
      an edge slightly sunk rather than elevated.

PMID- 16282583
TI  - A comparison of bone-patellar tendon-bone and bone-hamstring tendon-bone
      autografts for anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Most of the previous comparative studies between patellar tendon and
      hamstring tendon anterior cruciate ligament grafts compared grafts of different
      constructs fixed with different methods. PURPOSE: To compare patellar tendon and
      hamstring tendon grafts with the same fixation method used to reconstruct the
      anterior cruciate ligament. STUDY DESIGN: Randomized controlled trial; Level of
      evidence, 1. METHODS: During the reconstructive procedure, the hamstring tendon
      graft was prepared as a bone-hamstring-bone graft; both bone-patellar tendon-bone
      and bone-hamstring-bone grafts were fixed with interference screws. Eighty
      consecutive patients who underwent anterior cruciate ligament reconstruction were
      randomly assigned to either bone-patellar tendon-bone or bone-hamstring-bone
      groups. Follow-up examinations were performed for at least 5 years
      postoperatively. Seventy-two of the 80 patients (37 patients in the bone-patellar
      tendon-bone group and 35 in the bone-hamstring-bone group) were evaluated, with a
      mean follow-up period of 87.0 and 80.8 months, respectively. Follow-up
      examinations were performed using the International Knee Documentation Committee
      knee ligament standard and subjective knee forms. RESULTS: The mean KT-1000
      arthrometer evaluation results showed no significant difference between the bone
      patellar tendon-bone and bone-hamstring-bone groups (1.2 +/- 2.1 mm and 1.7 +/-
      1.4 mm, respectively; P = .24). However, symptoms related to graft harvest
      (anterior kneeling pain) were more frequently observed in the bone-patellar
      tendon-bone group, and unsatisfactory results were correlated with severe
      kneeling pain in 3 patients from this group (P = .0056). Significant hamstring
      muscle weakness without complaint of functional deficit was found in the bone
      hamstring-bone group (P = .0045). CONCLUSION: Bone-hamstring-bone grafts were
      shown to reduce the risk of problems at the graft harvest site compared to bone
      patellar tendon-bone grafts, with comparable results in the remaining clinical
      parameters tested.

PMID- 16282584
TI  - Parameters determining the efficiency of gene targeting in the moss
      Physcomitrella patens.
AB  - In the moss Physcomitrella patens, transforming DNA containing homologous
      sequences integrates predominantly by homologous recombination with its genomic
      target. A systematic investigation of the parameters that determine gene
      targeting efficiency shows a direct relationship between homology length and
      targeting frequency for replacement vectors (a selectable marker flanked by
      homologous DNA). Overall homology of only 1 kb is sufficient to achieve a 50%
      yield of targeted transformants. Targeting may occur through homologous
      recombination in one arm, accompanied by non-homologous end-joining by the other
      arm of the vector, or by allele replacement following two homologous
      recombination events. Allele replacement frequency depends on the symmetry of the
      targeting vector, being proportional to the length of the shorter arm. Allele
      replacement may involve insertion of multiple copies of the transforming DNA,
      accompanied by ectopic insertions at non-homologous sites. Single-copy and single
      insertions at targeted loci (targeted gene replacements, 'TGR') occur with a
      frequency of 7-20% of all transformants when the minimum requirements for allele
      replacement are met. Homologous recombination in Physcomitrella is substantially
      more efficient than in any multicellular eukaryote, recommending it as the
      outstanding model for the study of homologous recombination in plants.

PMID- 16282585
TI  - Role of stacking interactions in the binding sequence preferences of DNA bis
      intercalators: insight from thermodynamic integration free energy simulations.
AB  - The major structural determinant of the preference to bind to CpG binding sites
      on DNA exhibited by the natural quinoxaline bis-intercalators echinomycin and
      triostin A, or the quinoline echinomycin derivative, 2QN, is the 2-amino group of
      guanine (G). However, relocation of this group by means of introduction into the
      DNA molecule of the 2-aminoadenine (=2,6-diaminopurine, D) base in place of
      adenine (A) has been shown to lead to a drastic redistribution of binding sites,
      together with ultratight binding of 2QN to the sequence DTDT. Also, the
      demethylated triostin analogs, TANDEM and CysMeTANDEM, which bind with high
      affinity to TpA steps in natural DNA, bind much less tightly to CpI steps,
      despite the fact that both adenosine and the hypoxanthine-containing nucleoside,
      inosine (I), provide the same hydrogen bonding possibilities in the minor groove.
      To study both the increased binding affinity of 2QN for DTDT relative to GCGC
      sites and the remarkable loss of binding energy between CysMeTANDEM and ICIC
      compared with ATAT, a series of thermodynamic integration free energy simulations
      involving conversions between DNA base pairs have been performed. Our results
      demonstrate that the electrostatic component of the stacking interactions between
      the heteroaromatic rings of these compounds and the bases that make up the
      intercalation sites plays a very important role in the modulation of their
      binding affinities.

PMID- 16282586
TI  - A coarse graining approach to determine nucleic acid structures from small angle
      neutron scattering profiles in solution.
AB  - We present a theoretical method to calculate the small angle neutron scattering
      profile of nucleic acid structures in solution. Our approach is sensitive to the
      sequence and the structure of the nucleic acid. In order to test our approach, we
      apply this method to the calculation of the experimental scattered intensity of
      the decamer d(CCAACGTTGG)2 in H2O. This sequence was specifically chosen for this
      study as it is believed to adopt a canonical B-form structure in 0.3 M NaCl. We
      find that not only will our methodology reproduce the experimental scattered
      intensity for this sequence, but our method will also discriminate between B-, A-
      and Z-form DNA. By studying the scattering profile of this structure in 0.5 and
      1.0 M NaCl, we are also able to identify tetraplex and other similar oligomers
      formation and to model the complex using the experimental scattering data in
      conjunction with our methodology.

PMID- 16282587
TI  - Shared RNA-binding sites for interacting members of the Drosophila ELAV family of
      neuronal proteins.
AB  - The product of the Drosophila embryonic lethal abnormal visual system is a
      conserved protein (ELAV) necessary for normal neuronal differentiation and
      maintenance. It possesses three RNA-binding domains and is involved in the
      regulation of RNA metabolism. The long elav 3'-untranslated region (3'-UTR) is
      necessary for autoregulation. We used RNA-binding assays and in vitro selection
      to identify the ELAV best binding site in the elav 3'-UTR. This site resembles
      ELAV-binding sites identified previously in heterologous targets, both for its
      nucleotide sequence and its significant affinity for ELAV (K(d) 40 nM). This
      finding supports our model that elav autoregulation depends upon direct
      interaction between ELAV and elav RNA. We narrowed down the best binding site to
      a 20 nt long sequence A(U5)A(U3)G(U2)A(U6) in an alternative 3' exon. We propose
      and test a model in which the regulated use of this alternative 3' exon is
      involved in normal elav regulation. Found in NEurons (FNE), another neuronal RNA
      binding protein paralogous to ELAV, also binds this site. These observations
      provide a molecular basis for the in vivo interactions reported previously
      between elav and fne.

PMID- 16282589
TI  - Silencing of retrotransposons in Dictyostelium by DNA methylation and RNAi.
AB  - We have identified a DNA methyltransferase of the Dnmt2 family in Dictyostelium
      that was denominated DnmA. Expression of the dnmA gene is downregulated during
      the developmental cycle. Overall DNA methylation in Dictyostelium is
      approximately 0.2% of the cytosine residues, which indicates its restriction to a
      limited set of genomic loci. Bisulfite sequencing of specific sites revealed that
      DnmA is responsible for methylation of mostly asymmetric C-residues in the
      retrotransposons DIRS-1 and Skipper. Disruption of the gene resulted in a loss of
      methylation and in increased transcription and mobilization of Skipper. Skipper
      transcription was also upregulated in strains that had genes encoding components
      of the RNA interference pathway disrupted. In contrast, DIRS-1 expression was not
      affected by a loss of DnmA but was strongly increased in strains that had the RNA
      directed RNA polymerase gene rrpC disrupted. A large number of siRNAs were found
      that corresponded to the DIRS-1 sequence, suggesting concerted regulation of DIRS
      1 expression by RNAi and DNA modification. No siRNAs corresponding to the
      standard Skipper element were found. The data show that DNA methylation plays a
      crucial role in epigenetic gene silencing in Dictyostelium but that different,
      partially overlapping mechanisms control transposon silencing.

PMID- 16282588
TI  - T:G mismatch-specific thymine-DNA glycosylase (TDG) as a coregulator of
      transcription interacts with SRC1 family members through a novel tyrosine repeat
      motif.
AB  - Gene activation involves protein complexes with diverse enzymatic activities,
      some of which are involved in chromatin modification. We have shown previously
      that the base excision repair enzyme thymine DNA glycosylase (TDG) acts as a
      potent coactivator for estrogen receptor-alpha. To further understand how TDG
      acts in this context, we studied its interaction with known coactivators of
      nuclear receptors. We find that TDG interacts in vitro and in vivo with the p160
      coactivator SRC1, with the interaction being mediated by a previously undescribed
      motif encoding four equally spaced tyrosine residues in TDG, each tyrosine being
      separated by three amino acids. This is found to interact with two motifs in SRC1
      also containing tyrosine residues separated by three amino acids. Site-directed
      mutagenesis shows that the tyrosines encoded in these motifs are critical for the
      interaction. The related p160 protein TIF2 does not interact with TDG and has the
      altered sequence, F-X-X-X-Y, at the equivalent positions relative to SRC1.
      Substitution of the phenylalanines to tyrosines is sufficient to bring about
      interaction of TIF2 with TDG. These findings highlight a new protein-protein
      interaction motif based on Y-X-X-X-Y and provide new insight into the interaction
      of diverse proteins in coactivator complexes.

PMID- 16282591
TI  - Pyrimido[1,2-a]-purin-10(3H)-one, M1G, is less prone to artifact than base
      oxidation.
AB  - Pyrimido[1,2-a]-purin-10(3H)-one (M1G) is a secondary DNA damage product arising
      from primary reactive oxygen species (ROS) damage to membrane lipids or
      deoxyribose. The present study investigated conditions that might lead to
      artifactual formation or loss of M1G during DNA isolation. The addition of
      antioxidants, DNA isolation at low temperature or non-phenol extraction methods
      had no statistically significant effect on the number of M1G adducts measured in
      either control or positive control tissue samples. The number of M1G adducts in
      nuclear DNA isolated from brain, liver, kidney, pancreas, lung and heart of
      control male rats were 0.8, 1.1, 1.1, 1.1, 1.8 and 4.2 M1G/10(8) nt,
      respectively. In rat liver tissue, the mitochondrial DNA contained a 2-fold
      greater number of M1G adducts compared with nuclear DNA. Overall, the results
      from this study demonstrated that measuring M1G is a reliable way to assess
      oxidative DNA damage because the number of M1G adducts is significantly affected
      by the amount of ROS production, but not by DNA isolation procedures. In
      addition, this study confirmed that the background number of M1G adducts reported
      in genomic DNA could have been overestimated by one to three orders of magnitude
      in previous reports.

PMID- 16282590
TI  - Invariant amino acids essential for decoding function of polypeptide release
      factor eRF1.
AB  - In eukaryotic ribosome, the N domain of polypeptide release factor eRF1 is
      involved in decoding stop signals in mRNAs. However, structure of the decoding
      site remains obscure. Here, we specifically altered the stop codon recognition
      pattern of human eRF1 by point mutagenesis of the invariant Glu55 and Tyr125
      residues in the N domain. The 3D structure of generated eRF1 mutants was not
      destabilized as demonstrated by calorimetric measurements and calculated free
      energy perturbations. In mutants, the UAG response was most profoundly and
      selectively affected. Surprisingly, Glu55Arg mutant completely retained its
      release activity. Substitution of the aromatic ring in position 125 reduced
      response toward all stop codons. This result demonstrates the critical importance
      of Tyr125 for maintenance of the intact structure of the eRF1 decoding site. The
      results also suggest that Tyr125 is implicated in recognition of the 3d stop
      codon position and probably forms an H-bond with Glu55. The data point to a
      pivotal role played by the YxCxxxF motif (positions 125-131) in purine
      discrimination of the stop codons. We speculate that eRF1 decoding site is formed
      by a 3D network of amino acids side chains.

PMID- 16282592
TI  - Crystal structure and RNA binding of the Rpb4/Rpb7 subunits of human RNA
      polymerase II.
AB  - The Rpb4 and Rpb7 subunits of eukaryotic RNA polymerase II (RNAP(II)) form a
      heterodimer that protrudes from the 10-subunit core of the enzyme. We have
      obtained crystals of the human Rpb4/Rpb7 heterodimer and determined the structure
      to 2.7 A resolution. The presence of putative RNA-binding domains on the Rpb7
      subunit and the position of the heterodimer close to the RNA exit groove in the
      12 subunit yeast polymerase complex strongly suggests a role for the heterodimer
      in binding and stabilizing the nascent RNA transcript. We have complemented the
      structural analysis with biochemical studies directed at dissecting the RNA
      binding properties of the human Rpb4/Rpb7 complex and that of the homologous E/F
      complex from Methanocaldococcus jannaschii. A number of conserved, solvent
      exposed residues in both the human Rpb7 subunit and the archaeal E subunit have
      been modified by site-directed mutagenesis and the mutants tested for RNA binding
      by performing electrophoretic mobility shift assays. These studies have
      identified an elongated surface region on the corresponding face of both subunit
      E and Rpb7 that is involved in RNA binding. The area spans the nucleic acid
      binding face of the OB fold, including the B4-B5 loop, but also extends towards
      the N-terminal domain.

PMID- 16282594
TI  - Neuropeptide S and its receptor: a newly deorphanized G protein-coupled receptor
      system.
AB  - Neuropeptide S (NPS) is a recently discovered bioactive peptide that has shed new
      light on the neurobiology of sleep/wakefulness regulation and anxiety-like
      behavior. NPS can potently promote arousal and suppress all stages of sleep. This
      effect might be modulated by NPS receptors expressed in thalamic centers that are
      relays for transmitting arousing stimuli originating from the brainstem to the
      cortex. The peptide precursor is expressed most prominently in a novel nucleus
      located directly adjacent to the noradrenergic locus coeruleus, a brain structure
      with well-defined functions in arousal, stress, and anxiety. NPS was also found
      to induce anxiolytic-like behavior in a battery of four different tests of innate
      responses to stress. This unique pharmacological profile of NPS offers
      significant potential for developing new drugs for the treatment of sleep and/or
      anxiety disorders.

PMID- 16282593
TI  - Myelination: an overlooked mechanism of synaptic plasticity?
AB  - Myelination of the brain continues through childhood into adolescence and early
      adulthood--the question is, Why? Two new articles provide intriguing evidence
      that myelination may be an underappreciated mechanism of activity-dependent
      nervous system plasticity: one study reported increased myelination associated
      with extensive piano playing, another indicated that rats have increased
      myelination of the corpus callosum when raised in environments providing
      increased social interaction and cognitive stimulation. These articles make it
      clear that activity-dependent effects on myelination cannot be considered
      strictly a developmental event. They raise the question of whether myelination is
      an overlooked mechanism of activity-dependent plasticity, extending in humans
      until at least age 30. It has been argued that regulating the speed of conduction
      across long fiber tracts would have a major influence on synaptic response, by
      coordinating the timing of afferent input to maximize temporal summation. The
      increase in synaptic amplitude could be as large as neurotransmitter-based
      mechanisms of plasticity, such as LTP. These new findings raise a larger
      question: How did the oligodendrocytes know they were practicing the piano or
      that their environment was socially complex?

PMID- 16282595
TI  - Altered gene expression profiles reveal similarities and differences between
      Parkinson disease and model systems.
AB  - Parkinson disease (PD) targets dopaminergic neurons in the substantia nigra,
      resulting in motor disturbances such as resting tremor, bradykinesia, and
      rigidity. Pathogenic processes likely occur over several decades, in that an
      overwhelming percentage of neurons are already dead at the time of clinical
      diagnosis. For this reason, the usage of animal model systems to discover the
      early steps in the pathologic cascade is required. These include exposure to the
      neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which selectively
      kills dopamine neurons in the substantia nigra, and genetic models incorporating
      mutations in the alpha-synuclein gene that cause disease in human patients.
      Through the evaluation of these models at multiple time points, it is possible to
      discover novel gene expression changes that may underlie disease pathogenesis.
      Specifically, the authors hypothesize that animal models of PD and human PD
      brains share a gene expression profile that signifies certain aspects of
      pathogenesis and/or recovery-resistance. To test this and similar hypotheses, the
      authors and others have utilized new microarray technology that enables the
      sampling of thousands of genes' expression level in one assay. Because the
      technology is fairly new and results can vary depending on methods used, results
      must be evaluated with care. Multiple array and data-mining options can be used
      to make the most accurate inferences as to differentially expressed genes in each
      set of samples. The authors developed a fusion classifier approach whereby
      individual data-mining algorithms generate lists of significant genes. The lists
      are subsequently queried, and only genes unanimously called significant are
      retained for further validation. Although the authors' approach identified
      hundreds of differentially expressed genes in each of three PD systems, only a
      few were common between the human and animal substantia nigra. These were related
      to dopamine phenotype, synaptic function, and the mitochondrial metabolism,
      implicating the presynaptic terminal as a primary site of injury. The time course
      of the authors' experiments indicates that if the synaptic changes could be
      prevented, this may alleviate some cell death, in that these changes precede
      neuronal loss.

PMID- 16282596
TI  - Potassium channels, memory T cells, and multiple sclerosis.
AB  - Multiple sclerosis is a chronic inflammatory autoimmune disease of the central
      nervous system characterized by demyelination and axonal damage that result in
      disabling neurological deficits. Here the authors explain the rationale for the
      use of inhibitors of the Kv1.3 K+ channel in immune cells as a therapy for
      multiple sclerosis and other autoimmune disorders.

PMID- 16282597
TI  - The p300: where in the brain is it produced and what does it tell us?
AB  - Intracranial recordings, lesion studies, and the combination of functional
      imaging with source analysis have produced a solid body of evidence about the
      generators of the P300 event-related potential. Although it is impossible to
      square all findings obtained across and within methodologies, a consistent
      pattern of generators has emerged, with target-related responses in the parietal
      cortex and the cingulate and novelty-related activations mainly in the inferior
      parietal and prefrontal regions. Stimulus modality-specific contributions come
      from the inferior temporal and superior parietal cortex for the visual and from
      the superior temporal cortex for the auditory modality. The P300 continues to be
      an important signature of cognitive processes such as attention and working
      memory and of its dysfunction in neurologic and mental disorders. It is
      increasingly being investigated as a potential genetic marker of mental
      disorders. Knowledge about the generators of the P300 will be crucial for a
      better understanding of its cognitive significance and its continuing clinical
      application.

PMID- 16282598
TI  - How the blind "see" Braille: lessons from functional magnetic resonance imaging.
AB  - What does the visual cortex of the blind do during Braille reading? This process
      involves converting simple tactile information into meaningful patterns that have
      lexical and semantic properties. The perceptual processing of Braille might be
      mediated by the somatosensory system, whereas visual letter identity is
      accomplished within the visual system in sighted people. Recent advances in
      functional neuroimaging techniques, such as functional magnetic resonance
      imaging, have enabled exploration of the neural substrates of Braille reading.
      The primary visual cortex of early-onset blind subjects is functionally relevant
      to Braille reading, suggesting that the brain shows remarkable plasticity that
      potentially permits the additional processing of tactile information in the
      visual cortical areas.

PMID- 16282599
TI  - The ubiquitin-proteasome system in Huntington's disease.
AB  - The main histopathological feature of Huntington's disease (HD) is the presence
      of protein aggregates that are gathered into inclusion bodies. So far the
      mechanisms that lead to inclusion formation as well as their role in the
      pathogenesis of HD are not totally understood. However, it is well established
      that inclusion bodies contain components of the ubiquitin-proteasome system.
      Accordingly, it has been postulated that impairment of this machinery can be one
      of the causes of this disorder. In this review, the authors summarize the state
      of current knowledge about this hypothesis.

PMID- 16282600
TI  - Christine Petit, MD, PhD, head of an Institut Pasteur-Inserm unit, wins Bristol
      Myers Squibb Neuroscience Research Award: recognized for discovering the
      molecular basis of hearing and the genetic causes of deafness.

PMID- 16282603
TI  - LacdiNAc- and LacNAc-containing glycans induce granulomas in an in vivo model for
      schistosome egg-induced hepatic granuloma formation.
AB  - Schistosomes, major parasitic helminths, express numerous glycoconjugates that
      provoke humoral and cellular immune responses in the infected human host. The
      main pathology in schistosomiasis is due to the formation of granulomas around
      tissue-trapped eggs and the resulting organ damage. By using a mouse model of
      induction of granulomas by hepatic implantation of antigen-coated beads, it has
      been determined that the glycan part of schistosomal soluble egg antigens (SEA)
      initiates granulomogenesis. To identify which individual glycan elements in this
      complex SEA mixture are granulomogenic, we have tested in the same mouse model
      conjugates of various synthetic oligosaccharides characteristic for schistosome
      eggs, including GalNAcbeta1-4GlcNAc (LacdiNAc, LDN), Galbeta1-4(Fucalpha1
      3)GlcNAc (Lewisx), Fucalpha1-2Fucalpha1-3GlcNAc (DF-Gn), and Fucalpha1
      3GalNAcbeta1-4(Fucalpha1-3)GlcNAc (F-LDN-F). Ribonuclease (RNase) A and B, and
      different fetuin glycoforms were included as controls. Only beads that carry
      glycoconjugates with terminal LacdiNAc or Galbeta1-4GlcNAc (LacNAc, LN) elements
      gave rise to granulomas, with macrophage, lymphocyte, and eosinophil levels
      similar to the granulomatous lesions caused by schistosome eggs in a natural
      infection. Uncoated beads, and beads coated with fucosylated glycoconjugates or
      glycoconjugates lacking terminally exposed Gal or GalNAc, only attracted a
      monolayer of macrophages. These results indicate that the formation of hepatic
      granulomas is triggered specifically by glycoconjugates which carry terminal
      LacNAc or LacdiNAc, both constituents of the schistosome egg.

PMID- 16282604
TI  - CEACAM1, an adhesion molecule of human granulocytes, is fucosylated by
      fucosyltransferase IX and interacts with DC-SIGN of dendritic cells via Lewis x
      residues.
AB  - The CEA-related cell adhesion molecule 1, CEACAM1, is a glycoprotein expressed on
      the surface of human granulocytes and lymphocytes, endothelia, and many
      epithelia. CEACAM1 is involved in the regulation of important biological
      processes, such as tumor growth, angiogenesis, and modulation of the immune
      response. CEACAM1, a member of the immunoglobulin superfamily carries several
      Lewis x (Lex) structures as we recently demonstrated by mass spectrometry of
      native CEACAM1 from human granulocytes. Since Lex residues of pathogens bind to
      the C-type lectin dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN)
      expressed on human DCs, we hypothesized that Lex glycans of CEACAM1 are
      recognized by DC-SIGN. Here, we demonstrate that CEACAM1, the major carrier of
      Lex residues in human granulocytes, is specifically recognized by DC-SIGN via Lex
      residues mediating the internalization of CEACAM1 into immature DCs. Expression
      studies with CEACAM1 in combination with different fucosyltransferases (FUTs)
      revealed that FUTIX plays a key role in the synthesis of Lex groups of CEACAM1.
      As Lex groups on CEACAM1 are selectively attached and specifically interact with
      DC-SIGN, our findings suggest that CEACAM1 participates in immune regulation in
      physiological conditions and in pathological conditions, such as inflammation,
      autoimmune disease, and cancer.

PMID- 16282605
TI  - Synthetic lactulose amines: novel class of anticancer agents that induce tumor
      cell apoptosis and inhibit galectin-mediated homotypic cell aggregation and
      endothelial cell morphogenesis.
AB  - Galectins, a family of structurally related carbohydrate-binding proteins,
      contribute to different events associated with cancer biology, including
      apoptosis, homotypic cell aggregation, angiogenesis and tumor-immune escape. To
      interfere with galectin-carbohydrate interactions during tumor progression, a
      current challenge is the design of specific galectin inhibitors for therapeutic
      purposes. Here, we report the synthesis of three novel low molecular weight
      synthetic lactulose amines (SLA): (1) N-lactulose-octamethylenediamine (LDO), (2)
      N,N'-dilactulose-octamethylenediamine (D-LDO), and (3) N,N'-dilactulose
      dodecamethylenediamine (D-LDD). These compounds showed a differential ability to
      inhibit binding of galectin-1 and/or galectin-3 to the highly glycosylated
      protein 90K in solid-phase assays. In addition, each compound demonstrated
      selective regulatory effects in different events linked to tumor progression
      including tumor-cell apoptosis, homotypic cell aggregation, and endothelial cell
      morphogenesis. Our results suggest that galectin inhibitors with subtle
      differences in their carbohydrate structures may be potentially used to
      specifically block different steps of tumor growth and metastasis.

PMID- 16282606
TI  - A monoclonal antibody against a carbohydrate epitope in lipopolysaccharide
      differentiates Chlamydophila psittaci from Chlamydophila pecorum, Chlamydophila
      pneumoniae, and Chlamydia trachomatis.
AB  - Lipopolysaccharide (LPS) of Chlamydophila psittaci but not of Chlamydophila
      pneumoniae or Chlamydia trachomatis contains a tetrasaccharide of 3-deoxy-alpha-d
      manno-oct-2-ulopyranosonic acid (Kdo) of the sequence Kdo(2-->8)[Kdo(2-->4)]
      Kdo(2-->4)Kdo. After immunization with the synthetic neoglycoconjugate antigen
      Kdo(2-->8)[Kdo(2-->4)]Kdo(2-->4) Kdo-BSA, we obtained the mouse monoclonal
      antibody (mAb) S69-4 which was able to differentiate C. psittaci from
      Chlamydophila pecorum, C. pneumoniae, and C. trachomatis in double labeling
      experiments of infected cell monolayers and by enzyme-linked immunosorbent assay
      (ELISA). The epitope specificity of mAb S69-4 was determined by binding and
      inhibition assays using bacteria, LPS, and natural or synthetic Kdo
      oligosaccharides as free ligands or conjugated to BSA. The mAb bound
      preferentially Kdo(2-->8)[Kdo(2-->4)]Kdo(2-->4)Kdo(2-->4) with a K(d) of 10
      microM, as determined by surface plasmon resonance (SPR) for the monovalent
      interaction using mAb or single chain Fv. Cross-reactivity was observed with
      Kdo(2-->4)Kdo(2-->4) Kdo but not with Kdo(2-->8)Kdo(2-->4)Kdo, Kdo disaccharides
      in 2-->4- or 2-->8-linkage, or Kdo monosaccharide. MAb S69-4 was able to detect
      LPS on thin-layer chromatography (TLC) plates in amounts of <10 ng by
      immunostaining. Due to the high sensitivity achieved in this assay, the antibody
      also detected in vitro products of cloned Kdo transferases of Chlamydia. The
      antibody can therefore be used in medical and veterinarian diagnostics, general
      microbiology, analytical biochemistry, and studies of chlamydial LPS
      biosynthesis. Further contribution to the general understanding of carbohydrate
      binding antibodies was obtained by a comparison of the primary structure of mAb
      S69-4 to that of mAb S45-18 of which the crystal structure in complex with its
      ligand has been elucidated recently (Nguyen et al., 2003, Nat. Struct. Biol., 10,
      1019-1025).

PMID- 16282607
TI  - Critique of "Evaluation of procedures to predict fat-free lean in swine
      carcasses".

PMID- 16282609
TI  - Effect of the porcine IGF2-intron3-G3072A substitution in an outbred Large White
      population and in an Iberian x Landrace cross.
AB  - The IGF2-intron3-G3072A substitution has been recently described as the causal
      factor of the imprinted QTL for fat deposition and muscle growth detected within
      the porcine IGF2 region. The objective of this study was to investigate the IGF2
      substitution effect in a Large White outbred population and in an Iberian x
      Landrace F2 cross. The results showed that the substitution has significant
      effects on fatness, growth, and shape traits with estimated effects in the
      expected direction. These results agree with those obtained in the F2 cross,
      where the IGF2-intron3-G3072A substitution is segregating only in a small family.
      In addition, a QTL scan has been performed in the F2 population for the traits
      used in the IGF2 substitution effect validation. Results of this study
      demonstrated that there are QTL segregating in swine chromosome 2 other than the
      IGF2 substitution for carcass weight, LM area, and pH measured at 24 h after
      slaughter. The results confirm the relevance of the IGF2 substitution, but they
      also show that there are still valuable mutations to be revealed in this
      chromosome.

PMID- 16282610
TI  - Meat quality traits were unaffected by a quantitative trait locus affecting leg
      composition traits in Texel sheep.
AB  - A QTL affecting leg muscle and fat traits has been identified within the New
      Zealand Texel population. The QTL maps to a region on OAR 2 with a two-marker
      haplotype test established at markers BULGE20 and BM81124. These markers
      encompass the likely position of Growth Differentiation Factor 8 (GDF8). The
      pleiotropic effects of this QTL on meat quality traits are tested. Objective
      measures of meat quality including pH, color (L*, a*, and b*), and tenderness (as
      assessed by Warner-Bratzler shear force measurements) were assessed on
      longissimus and semi-membranosus muscles of 540 progeny from six Texel sires.
      Four of these sires were subsequently identified as segregating for leg muscle
      and fat traits. For these segregating sires, comparison of progeny that had
      inherited the favorable haplotype from their sire with those that had received
      the alternate haplotype revealed no significant differences in the meat quality
      traits assessed. This finding suggests that the muscling QTL does not have
      pleiotropic effects on meat quality. A general scan for meat quality QTL was
      carried out using genotype data for eight markers from FCB128 to RM356 flanking
      122cM of OAR 2 using Haley-Knott regression. This analysis revealed two QTL for a
      single sire. A QTL detected in the region of Marker INRA40 for color L* mapped to
      a site close to the muscling QTL, but there was evidence to suggest it is at a
      distinct locus. The QTL in the region of Marker RM356 might map distal to Marker
      RM356, as no peak was observed. This QTL, which seems to affect pH, color a*,
      color b*, and Warner-Bratzler shear measurements, requires further
      characterization.

PMID- 16282611
TI  - Joint longitudinal modeling of age of dam and age of animal for growth traits in
      beef cattle.
AB  - Two methods to jointly model age of dam (AOD) and age of animal in random
      regression analyses of growth in Gelbvieh cattle were examined. The first method
      (M1) was analogous to the multiple-trait analysis and consisted of AOD as a
      nested class variable and a cubic polynomial regression on age nested within
      birth, weaning, and yearly weights. The second method (M2) used two-dimensional
      splines, with age knots at 150, 205, 270, 340, and 390 d. The AOD knots were
      placed at 725, 1,464, and 2,189 d. These selected knots were used to form a two
      dimensional grid containing 15 knots, each representing a specific age and AOD
      combination. A data set containing Gelbvieh growth records was split along
      contemporary groups into two data sets. Data set 1 contained 316,078 records and
      was used for prediction by mixed-model equations. Data set 2 contained 164,167
      records and was used for cross validation. In the complete data set, only 90 and
      30% of animals with birth weight had records on weaning and yearling weights,
      respectively. Models were evaluated based on R2, average squared error (ASE),
      percent bias, and plots of solutions. The ASE for weights associated with birth
      weight, weaning weight, and yearling weight for M1 were 15, 505, and 703 kg2.
      With M2, large jumps in fixed-effect estimates were observed outside the two
      dimensional grid. To eliminate this problem, weighted one-dimensional splines
      were used for extrapolation beyond the two-dimensional grid. For M2 with weighted
      spline extrapolation, the ASE were 15, 542, and 777 kg2 for birth weight, weaning
      weight, and yearling weight, respectively. Creation of optimal two-dimensional
      splines is difficult when data are clustered. Despite such difficulties, the two
      dimensional spline was capable of jointly and continuously modeling AOD and age
      of animal.

PMID- 16282612
TI  - Evaluation of Dorset, Finnsheep, Romanov, Texel, and Montadale breeds of sheep:
      V. Reproduction of F1 ewes in spring mating seasons.
AB  - Objectives were to estimate effects of sire breed (Dorset, Finnsheep, Romanov,
      Texel, and Montadale), dam breed [Composite III (CIII) and northwestern whiteface
      (WF)], mating season (March and May), and their interactions on reproductive
      traits of mature F1 ewes in spring mating seasons. A total of 1,099 F1 ewes
      produced 1,754 litters of 2,995 lambs from exposures to Suffolk rams during March
      and May mating seasons in 1995 through 1999. Fertility rate and ewe longevity
      were measured. Number born and litter birth weight were recorded, and number and
      weight at weaning and 20 wk of age were analyzed separately for dam- and nursery
      reared litter mates. Total productivity from 4 to 6 yr of age for each ewe
      entering the breeding flock was calculated as the sum of 20-wk weights for dam
      reared lambs and separately for nursery-reared lambs. Interactions of sire breed
      x mating season, ewe age x mating season, and ewe age x dam breed were often
      significant. Interactive effects of sire breed and mating season on fertility
      rate (P < 0.001) were primarily due to differences in magnitude. Fertility rates
      of sire breeds for March and May matings, respectively, were 92 and 89% for
      Romanov, 91 and 72% for Finnsheep, 90 and 52% for Texel, 88 and 52% for
      Montadale, and 83 and 62% for Dorset. Sire breed x mating season also affected
      number born (P < 0.03); March and May values were 2.12 and 2.05 for Romanov, 2.00
      and 1.94 for Finnsheep, 1.39 and 1.41 for Texel, 1.37 and 1.51 for Montadale, and
      1.37 and 1.55 for Dorset, respectively. Interaction of sire breed x dam breed on
      fertility rate (P < 0.01) was due to change in rank as well as magnitude. Romanov
      and Dorset-sired ewes out of CIII dams had greater fertility rates than Romanov-
      and Dorset-sired ewes out of WF dams. The opposite situation existed for ewes by
      Finnsheep, Texel, and Montadale sires. Differences between dam breeds (CIII and
      WF) in total productivity of dam-reared lambs were not detected, whereas ewes
      exposed in March (78 kg) were more productive (P < 0.01) than those exposed in
      May (68 kg). Means of sire breeds for total productivity of dam-reared lambs were
      47, 65, 70, 70, and 111 kg for Texel, Montadale, Dorset, Finnsheep, and Romanov,
      respectively (P < 0.001). Superior reproduction of Romanov sired ewes was
      primarily due to greater fertility rate and prolificacy at each mating season and
      ewe age. Use of Romanov-crossbred ewes would increase fertility during spring
      mating, an important constraint of the sheep industry.

PMID- 16282614
TI  - Effects of dietary zinc and iron supplementation on mineral excretion, body
      composition, and mineral status of nursery pigs.
AB  - Two experiments were conducted to evaluate the effects of dietary Zn and Fe
      supplementation on mineral excretion, body composition, and mineral status of
      nursery pigs. In Exp. 1 (n = 24; 6.5 kg; 16 to 20 d of age) and 2 (n = 24; 7.2
      kg; 19 to 21 d of age), littermate crossbred barrows were weaned and allotted
      randomly by BW, within litter, to dietary treatments and housed individually in
      stainless steel pens. In Exp. 1, Phases 1 (d 0 to 7) and 2 (d 7 to 14) diets (as
      fed basis) were: 1) NC (negative control, no added Zn source); 2) ZnO (NC + 2,000
      mg/kg as Zn oxide); and 3) ZnM (NC + 2,000 mg/kg as Zn Met). In Exp. 2, diets for
      each phase (Phase 1 = d 0 to 7; Phase 2 = d 7 to 21; Phase 3 = d 21 to 35) were
      the basal diet supplemented with 0, 25, 50, 100, and 150 mg/kg Fe (as-fed basis)
      as ferrous sulfate. Orts, feces, and urine were collected daily in Exp. 1;
      whereas pigs had a 4-d adjustment period followed by a 3-d total collection
      period (Period 1 = d 5 to 7; Period 2 = d 12 to 14; Period 3 = d 26 to 28) during
      each phase in Exp. 2. Blood samples were obtained from pigs on d 0, 7, and 14 in
      Exp. 1 and d 0, 7, 21, and 35 in Exp. 2 to determine hemoglobin (Hb), hematocrit
      (Hct), and plasma Cu, (PCu), Fe (PFe), and Zn (PZn). Pigs in Exp. 1 were killed
      at d 14 (mean BW = 8.7 kg) to determine whole-body, liver, and kidney mineral
      concentrations. There were no differences in growth performance in Exp. 1 or 2.
      In Exp. 1, pigs fed ZnO or ZnM diets had greater (P < 0.001) dietary Zn intake
      during the 14-d study and greater fecal Zn excretion during Phase 2 compared with
      pigs fed the NC diet. Pigs fed 2,000 mg/kg, regardless of Zn source, had greater
      (P < 0.010) PZn on d 7 and 14 than pigs fed the NC diet. Whole-body Zn, liver Fe
      and Zn, and kidney Cu concentrations were greater (P < 0.010), whereas kidney Fe
      and Zn concentrations were less (P < 0.010) in pigs fed pharmacological Zn diets
      than pigs fed the NC diet. In Exp. 2, dietary Fe supplementation tended to
      increase (linear, P = 0.075) dietary DMI, resulting in a linear increase (P <
      0.050) in dietary Fe, Cu, Mg, Mn, P, and Zn intake. Subsequently, a linear
      increase (P < 0.010) in fecal Fe and Zn excretion was observed. Increasing
      dietary Fe resulted in a linear increase in Hb, Hct, and PFe on d 21 (P < 0.050)
      and 35 (P < 0.010). Results suggest that dietary Zn or Fe additions increase
      mineral status of nursery pigs. Once tissue mineral stores are loaded, dietary
      minerals in excess of the body's requirement are excreted.

PMID- 16282613
TI  - Growth rate, body composition, and meat tenderness in early vs. traditionally
      weaned beef calves.
AB  - One hundred forty spring-born Angus x Gelbvieh and purebred Angus steers were
      selected for study as early weaned (EW; average age at weaning = 90 +/- 30 d) or
      traditionally weaned (TW; average age at weaning = 174 +/- 37 d) steers that were
      non-implanted or implanted (Synovex-S, Fort Dodge Animal Health, Overland Park,
      KS). Initially, steers were sorted by age, sire, and farm, and then allotted
      randomly in a 2 x 2 factorial arrangement of treatments of EW implanted (EWI), EW
      nonimplanted (EWN), TW implanted (TWI), or TW nonimplanted (TWN). Ultrasound
      measurements (US) of LM area (LMA), 12th rib fat thickness (US-BF), and marbling
      (US-M) were collected every 28 d during the time that steers were on feed. At 202
      d of age, EW calves had larger US-LMA, US-BF, and BW than TW calves (37.9 vs.
      32.3 cm2, 0.38 vs. 0.26 cm, and 271.6 vs. 218.9 kg, respectively; P < 0.001). At
      slaughter, EW calves had heavier HCW (290.4 vs. 279.7 kg, respectively; P < 0.05)
      and greater USDA marbling scores (51.25 vs. 46.26, respectively; P < 0.05) than
      TW calves; more EW steers graded USDA Choice or greater (P = 0.05). However, no
      differences were detected in BW (P = 0.15), LMA (P = 0.39), BF (P = 0.45), or
      liver abscess scores (P = 0.41). Twenty-four implanted steers were selected from
      the original group of 140 and sorted into two slaughter groups of 12. Twelve
      implanted steers from each weaning group, matched in slaughter BW but differing
      in age, were subsampled at slaughter to assess the effect of weaning age and
      chronological age on muscle tenderness. Younger animals had lower Warner-Bratzler
      shear force values (P < 0.001) than older calves after 14 d of postmortem aging;
      however, no differences were found in tenderness after 21 d of aging.
      Furthermore, there was greater variance (P < 0.001) in Warner-Bratzler shear
      force values among younger, EW steers vs. older, TW steers. These data provide
      evidence that early weaning of beef calves may be used as a tool to more
      effectively manage the cow-calf production system without compromising the
      quality of the offspring.

PMID- 16282616
TI  - Amino acid supplementation improves muscle mass in aged and young horses.
AB  - The objective of the study was to evaluate the effect of supplementary AA on the
      ability to support muscle mass in aging horses. Sixteen horses of light horse
      type were used in a 2 x 2 factorial arrangement of treatments with two age groups
      [< or = 10 yr (average = 9.1 +/- 0.29 yr) and > or = 20 yr (average = 22.4 +/-
      0.87 yr)] and two diet groups [no supplementation (N) or supplementary lysine and
      threonine (S; 20.0 and 15 g/d, respectively)]. Horses were fed the diets for 14
      wk and received regular light exercise throughout the study. Body weight, BCS,
      and venous blood samples were taken every 2 wk. Plasma was analyzed for total
      protein, albumin, creatinine, urea N (PUN), and an AA profile, including 3-methyl
      histidine (3MH) and sulfur AA. Photographs of the horses taken at the start and
      at the end of the experiment were used to assign a subjective muscle mass score
      from 1 to 5 (1 = lowest to 5 = highest). There was no difference in BW caused by
      diet; however, the S-group horses tended (P = 0.064) to gain more weight (6.91 +/
      2.3 kg), and in fact, the N-group horses lost weight (- 11.76 +/- 5.2 kg) during
      the experiment. Repeated measures analysis revealed that BCS was lower for the
      aged vs. the young horses (P = 0.001) as well as for the S- vs. the N-group
      horses (P = 0.026). Subjective muscle mass scores were not different at the start
      of the experiment but were greater (P = 0.047) for the S-group horses (3.77 +/-
      0.13) at the end of the experiment compared with the N-group horses (3.28 +/-
      0.14). Plasma creatinine was greater (P = 0.032), and PUN was lower (P = 0.027),
      for S-group horses compared with N-group horses. Initial 3MH concentrations were
      not different; however, at the end of the experiment, 3MH was lower for the S
      group horses (P = 0.016) compared with the N-group horses. Plasma lysine and
      threonine concentrations were greater for S-group horses at the end of the
      experiment than for N-group horses (P = 0.023 and 0.009, respectively). Both 3MH
      and PUN concentrations were negatively correlated to lysine (R2 = 0.57 and 0.65,
      respectively) and threonine intake (R2 = 0.56 and 0.60, respectively) at the end
      of the study. These data suggest that horses receiving supplementary AA were able
      to maintain muscle mass better than those without supplementation, regardless of
      age, as evidenced by the improvement in muscle mass scores, lower BCS with no
      difference in BW, greater creatinine, and lower 3MH and PUN concentrations in the
      S-group horses.

PMID- 16282615
TI  - Effects of beta-glucan obtained from the Chinese herb Astragalus membranaceus and
      lipopolysaccharide challenge on performance, immunological, adrenal, and
      somatotropic responses of weanling pigs.
AB  - A total of 108 crossbred piglets (7.75 +/- 0.24 kg of BW) weaned at 28 d was used
      to study the interactive effects of beta-glucan obtained from the Chinese herb
      Astragalus membranaceus (AM) and Escherichia coli lipopolysaccharide (LPS)
      challenge on performance, immunological, adrenal, and somatotropic responses of
      weaned pigs. The treatments were in a 2 x 3 factorial arrangement; main effects
      were level of Astragalus membranaceus glucan (AMG; 0, 500, or 1,000 mg/kg; as-fed
      basis) and presence of immunological challenge (with or without LPS). The
      experiment included six replicate pens per treatment and three pigs per pen.
      Lipopolysaccharide challenges were conducted on d 7 and 21 of the trial. Blood
      samples were obtained from the vena cava from one pig per pen at 3 h after LPS
      challenge to determine plasma responses. Weight gain and feed:gain ratio were
      unaffected by glucan. However, there was a quadratic effect on feed intake (P <
      0.05): pigs fed 500 mg of glucan/kg had the highest feed intake. Immunological
      challenge with LPS decreased weight gain (P = 0.02). An interaction (P = 0.01 to
      0.09) between AMG and LPS was observed for glucose, IL-1beta, PGE2, and cortisol.
      Astragalus membranaceus glucan had a quadratic effect on the plasma
      concentrations of glucose, IL-1beta, PGE2, and cortisol (P < 0.05) after both LPS
      challenges. Plasma concentrations of glucose, IL-1beta, PGE2, and cortisol (P <
      0.05) were all increased in LPS-challenged pigs compared with the control pigs
      after both LPS challenges. The IGF-I concentrations were less for LPS-challenged
      pigs than for unchallenged pigs. The lymphocyte proliferation response of
      peripheral blood induced by 5 microg of concanavalin A/mL (P < 0.01) and IL-2
      bioactivity (P < 0.05) increased linearly with increasing addition of glucan.
      Pigs challenged with LPS had greater T-lymphocyte proliferation (P = 0.06) and IL
      2 bioactivity (P = 0.07) than unchallenged pigs after the first immunological
      challenge but not after the second. In conclusion, although glucan did not
      improve pig performance under the conditions of the present experiment, when
      included at 500 mg/kg, it decreased the release of inflammatory cytokine and
      corticosteroid and improved the lymphocyte proliferation response of weanling
      piglets via enhanced IL-2 bioactivity.

PMID- 16282617
TI  - Lysine requirement of finishing pigs administered porcine somatotropin by
      sustained-release implant.
AB  - To alleviate the need for daily injection of porcine somatotropin (pST), a
      sustained-release implant (pSTSR) was devised that continuously delivers a daily
      dose of 2 mg of pST for 42 d. Ninety-six white composite (Large White x Landrace)
      finishing barrows (83.6 +/- 1.2 kg BW) were assigned to receive zero or two pSTSR
      implants (4 mg pST/d) and to consume one of six diets differing in total Lys
      concentration (0.29, 0.52, 0.75, 0.98, 1.21, or 1.44%, as-fed basis). Diets were
      formulated to be isocaloric and based on the ideal protein concept. Pigs were
      housed individually, allowed ad libitum access to feed and water, and slaughtered
      at 112 kg of BW. The pSTSR affected neither ADG (P = 0.88) nor 10th rib LM area
      (LMA; P = 0.51), but it decreased (P < 0.01) ADFI, average backfat thickness,
      10th rib fat depth, weights of leaf fat and ham fat, improved (P < 0.05) G:F, and
      increased (P < 0.01) weights of four trimmed lean cuts (T-cuts), and percentages
      of ham lean and bone. Increasing total Lys increased ADG (quadratic; P < 0.05)
      and ADFI (linear; P < 0.01). The G:F, plasma urea N concentrations (PUN), and T
      cuts were affected by the interaction pSTSR x dietary Lys (P < 0.01). Without
      pSTSR, the G:F did not differ (P = 0.37) among pigs fed 0.52% and greater total
      Lys. With pSTSR, the G:F was less (P < 0.05) for pigs fed 0.52% than 0.98 and
      1.44% total Lys. Increases in dietary total Lys resulted in increased PUN (P <
      0.01), and incremental increases were less in pSTSR-implanted pigs. Maximal yield
      of T-cuts was at 0.98% dietary total Lys in nonimplanted pigs and 1.21% total Lys
      in pSTSR-implanted pigs. Estimates of total Lys requirements of pigs without and
      with pSTSR, respectively, were 0.52 and 0.86% for growth (ADG and G:F) and 0.73
      and 0.88% for lean production (LMA and T-cuts). Equivalent apparent ileal
      digestible Lys requirements of pigs without and with pSTSR, respectively, were
      0.44 and 0.68% for growth, and 0.62 and 0.75% for lean production. With ADFI of
      3.5 kg daily, an intake of approximately 26.1 g of total daily Lys (0.75%) or
      22.4 g of apparent ileal digestible Lys is needed to maximize lean production in
      finishing barrows receiving 4 mg pST/d via sustained-release implant.

PMID- 16282618
TI  - Optimal wet corn gluten and protein levels in steam-flaked corn-based finishing
      diets for steer calves.
AB  - A feeding trial evaluated the hypothesis that wet corn gluten feed would improve
      growth performance of cattle fed steam-flaked corn-based finishing diets and
      supply required degradable intake protein (DIP). The trial used 360 steer calves
      (initial BW = 288 +/- 11 kg) housed in 36 pens for 166 d in an incomplete 4 x 3
      factorial arrangement of treatments. Pens of steers were assigned to treatments
      according to a completely randomized design (four replicates per treatment
      combination). Treatments were wet corn gluten feed (0, 20, 30, or 40% of dietary
      DM) and CP (13.0, 13.7, or 14.4% of dietary DM) via supplemental urea as DIP. The
      0% wet corn gluten feed treatment included only the 13.7% CP diet, and the 40%
      wet corn gluten feed treatment included only the 13.7 and 14.4% CP diets. Final
      dietary DIP concentration was 9.0% for 0% wet corn gluten feed; 8.7, 9.5, and
      10.2% for 20% wet corn gluten feed; 9.0, 9.7, and 10.3% DIP for 30% wet corn
      gluten feed; and 10.0 and 10.6% for 40% wet corn gluten feed. Hot carcass weight,
      ADG, DMI, and G:F responded quadratically (P < or = 0.05) to wet corn gluten
      feed. The 20, 30, and 40% wet corn gluten feed treatments increased ADG by 7, 6,
      and 3% and increased DMI by 4, 5, and 5%, respectively, relative to the 0% wet
      corn gluten feed treatment. Feed efficiency was 102, 101, and 98% of the 0% wet
      corn gluten feed treatment for 20, 30, and 40% wet corn gluten feed,
      respectively. Hot carcass weight, ADG, and G:F increased linearly (P < or = 0.05)
      in response to increased DIP. Nonlinear analysis for DIP over the combined 20 and
      30% wet corn gluten feed treatments indicated a DIP requirement of 9.6% of DM for
      ADG and 9.2% of DM for G:F, corresponding to 14.6 and 14.3% CP for 20% wet corn
      gluten feed and 14.8 and 14.5% CP for 30% wet corn gluten feed, respectively. Fat
      thickness, marbling, LM area, and USDA yield grade were not affected (P = 0.12 to
      0.99) by wet corn gluten feed or CP. These results show that the inclusion rate
      of wet corn gluten feed for maximizing ADG and G:F in steam-flaked corn-based
      finishing diets is approximately 20% of DM. The DIP requirement determined in
      this trial averaged 9.4% of DM.

PMID- 16282619
TI  - Effects of pasteurization of potato slurry by-product fed in corn-or barley-based
      beef finishing diets.
AB  - Pasteurization of vegetable by-products such as potato slurry (PS) before feeding
      may be necessary to prevent the spread of pathogens and beef carcass blemishes.
      We hypothesized that pasteurization would increase ruminal fermentability of PS
      starch. Four ruminally cannulated crossbred beef steers (initial BW = 432) were
      used in a 4 x 4 Latin square experiment with a 2 x 2 factorial arrangement of
      treatments to examine the main effects and interactions of pasteurization (54.4
      degrees C for 2 h) of PS and grain type (GT; dry-rolled corn and barley) on
      ruminal and total tract digestion of beef finishing diets. Diets contained 7%
      alfalfa hay and 14% PS (DM basis) and were fed ad libitum three times daily. Corn
      based diets had 71.7% corn, whereas barley-based diets had 60% barley and 11.7%
      corn. Pasteurization resulted in greater (P = 0.004) soluble, rapidly degradable
      starch (34.3 vs. 26.7% for pasteurized and nonpasteurized PS, respectively).
      Ruminal fluid pH was more acidic (P < 0.07) for corn-based diets than for barley
      based diets (P = 0.07) at 0200 and 2100 (sample time x GT; P < 0.05). Ruminal
      fluid pH was more acidic (P = 0.06) at 1400 for corn-based diets containing
      pasteurized PS compared with other dietary treatments (sample time x
      pasteurization x GT; P = 0.04). Minimum and maximum ruminal pH were greater (P <
      0.10) for barley-based diets than for corn-based diets. Ruminal fluid pH was <
      6.0 for a greater (P = 0.04) proportion of the day for corn-based compared with
      barley-based diets. In vitro incubation measurements revealed that pasteurization
      of PS resulted in lower (P = 0.06) ruminal fluid ammonia N concentration. Ruminal
      fluid ammonia N concentration was lower (P = 0.11) for barley-based diets than
      for corn-based diets. Steers fed barley-based diets had greater (P = 0.02) DMI
      and lesser (P < 0.05) total tract digestibility of DM and ADF compared with
      steers fed corn diets. Pasteurization increased (P = 0.10) total tract starch
      digestibility. Results indicate pasteurization increased rapidly degradable
      starch, ruminal starch fermentability, and total tract starch digestibility of
      PS. Grain type interacted with pasteurization such that feeding corn-based diets
      containing pasteurized PS resulted in periodic reductions in ruminal pH. Feeding
      management may be more critical when feeding pasteurized PS in beef finishing
      diets.

PMID- 16282620
TI  - Effect of grain processing degree on intake, digestion, ruminal fermentation, and
      performance characteristics of steers fed medium-concentrate growing diets.
AB  - Three trials were conducted to evaluate the effects of degree of barley and corn
      processing on performance and digestion characteristics of steers fed growing
      diets. Trial 1 used 14 (328 +/- 43 kg initial BW) Holstein steers fitted with
      ruminal, duodenal, and ileal cannulas in a completely randomized design to
      evaluate intake, site of digestion, and ruminal fermentation. Treatments
      consisted of coarsely rolled barley (2,770 microm), moderately rolled barley
      (2,127 microm), and finely rolled barley (1,385 microm). Trial 2 used 141
      crossbred beef steers (319 +/- 5.5 kg initial BW; 441 +/- 5.5 kg final BW) fed
      for 84 d in a 2 x 2 factorial arrangement to evaluate the effects of grain source
      (barley or corn) and extent of processing (coarse or fine) on steer performance.
      Trial 3 investigated four degrees of grain processing in barley-based growing
      diets and used 143 crossbred steers (277 +/- 19 kg initial BW; 396 +/- 19 kg
      final BW) fed for 93 d. Treatments were coarsely, moderately, and finely rolled
      barley and a mixture of coarsely and finely rolled barley to approximate
      moderately rolled barley. In Trial 1, total tract digestibilities of OM, CP, NDF,
      and ADF were not affected (P > or = 0.10) by barley processing; however, total
      tract starch digestibility increased linearly (P < 0.05), and fecal starch output
      decreased linearly (P < 0.05) with finer barley processing. In situ DM, CP,
      starch disappearance rate, starch soluble fraction, and extent of starch
      digestion increased linearly (P < 0.05) with finer processing. In Trial 2, final
      BW and ADG were not affected by degree of processing or type of grain (P > or =
      0.13). Steers fed corn had greater DMI (P = 0.05) than those fed barley. In Trial
      3, DMI decreased linearly with finer degree of processing (P = 0.003). Gain
      efficiency, apparent dietary NEm, and apparent dietary NEg increased (P < 0.001)
      with increased degree of processing. Finer processing of barley improved
      characteristics of starch digestion and feed efficiency, but finer processing of
      corn did not improve animal performance in medium-concentrate, growing diets.

PMID- 16282621
TI  - Effects of grazing residues or feeding corn from a corn rootworm-protected hybrid
      (MON 863) compared with reference hybrids on animal performance and carcass
      characteristics.
AB  - One grazing and two feeding experiments were conducted to compare the feeding
      value of corn residue or corn grain from a genetically enhanced corn hybrid (corn
      rootworm-protected; event MON 863) with nontransgenic, commercially available,
      reference hybrids. In Exp. 1, two 13.7-ha fields, containing corn residues from
      either a genetically enhanced corn root-worm-protected hybrid (MON 863), or a
      near-isogenic, nontransgenic control hybrid (CON) were divided into four equal
      sized paddocks. Sixty-four steer calves (262 +/- 15 kg) were stratified by BW and
      assigned randomly to paddock to achieve a stocking rate of 0.43 ha/steer for 60
      d, with eight steers per paddock and 32 steers per hybrid. A protein supplement
      was fed at 0.45 kg/steer daily (DM basis) to ensure protein intake did not limit
      performance. Steer ADG did not differ (P = 0.30) between steers grazing the MON
      863 (0.39 kg/d) and CON (0.34 kg/d) corn residues for 60 d. The four treatments
      for the feeding experiments (Exp. 2 and 3) included two separate reference
      hybrids, the near-isogenic control hybrid (CON), and the genetically enhanced
      hybrid (MON 863) resulting in two preplanned comparisons of CON vs. MON 863, and
      MON 863 vs. the average of the reference hybrids (REF). In Exp. 2, 200 crossbred
      yearling steers (365 +/- 19 kg) were fed in 20 pens, with five pens per corn
      hybrid. In Exp. 3, 196 crossbred yearling steers (457 +/- 33 kg) were fed in 28
      pens, with seven pens per corn hybrid. In Exp. 2, DMI and G:F did not differ (P >
      0.10) between MON 863 and CON; however, steers fed MON 863 had a greater (P =
      0.04) ADG than steers fed CON. Gain efficiency was greater (P = 0.05) for MON 863
      cattle than for REF cattle in Exp. 2, but other performance measurements (DMI and
      ADG) did not differ (P > 0.10) between MON 863 and REF. No differences (P > 0.10)
      were observed for performance (DMI, ADG, and G:F) between MON 863 and CON or MON
      863 and REF in Exp. 3. In terms of carcass characteristics, no differences (P >
      0.10) were observed between MON 863 and CON, as well as MON 863 and REF, for
      marbling score, LM area, or 12th rib fat thickness in both Exp. 2 and 3. Overall,
      performance was not negatively affected in the corn residue grazing or feedlot
      experiments, suggesting the corn rootworm-protected hybrid (event MON 863) is
      similar to conventional, nontransgenic corn grain and residues when utilized by
      beef cattle.

PMID- 16282622
TI  - Intramuscular tenderness variation within four muscles of the beef chuck.
AB  - The i.m. tenderness variation was examined within four beef chuck muscles, the
      infraspinatus (IF), supraspinatus (SS), triceps brachii (TB), and serratus
      ventralis (SV). The IF, SS, TB, and SV muscles were cut into 2.5 cm thick steaks
      perpendicular to the long axis of the muscle. An identification tag was placed on
      each steak, consisting of a muscle identification number, steak number, and
      orientation of the steak. Steaks were vacuum-packaged and stored at -22 degrees C
      until subsequent analysis. Steaks were thawed at 1 degrees C and cooked on
      electric broilers to an internal temperature of 71 degrees C. One core was
      removed from each 2.5-cm x 2.5-cm section parallel to the muscle fiber and
      sheared once to determine Warner-Bratzler shear force (WBSF). The SS had an
      overall WBSF mean of 5.43 kg (SD = 2.20 kg) with no tenderness difference (P =
      0.43) among steak locations. The IF had an overall WBSF mean of 3.16 kg (SD =
      1.01 kg) with no tenderness difference (P = 0.51) among steak locations. The SV
      had a mean WBSF value of 4.37 kg (SD = 1.27 kg) with tenderness variation (P <
      0.05) among steak locations; however, tenderness variations were not dispersed in
      a discernible pattern. The TB had a mean WBSF value of 4.12 kg (SD = 1.26 kg)
      with lower (P < 0.05) shear force in the middle region of the TB, and the distal
      and proximal ends were tougher (P < 0.05). Results of this study provided a
      reasonably detailed mapping of the tenderness regions within the IF, SS, TB, and
      SV muscles, and this information could be used to add value to the beef chuck by
      cutting and marketing consistently tender regions.

PMID- 16282623
TI  - Duplication of the pale, soft, and exudative condition starting with normal
      postmortem pork.
AB  - The objective of the current study was to create an in vitro model that
      duplicated the development of PSE pork. Postrigor pork chops with various pH
      values and normal color were vacuum-packaged, and heated at approximately 42
      degrees C for various times (0, 15, 30, 60, 120, or 240 min), or heated to
      temperatures that occur early postmortem (34, 37, 39, or 42 degrees C for 60 or
      120 min) in a water bath. Chops were cooled and allowed to bloom, after which
      changes in Minolta and Hunter color values were assessed, and purge loss was
      determined. Warming postrigor pork with normal color and pH to early postmortem
      body temperature for various times successfully duplicated the characteristics of
      PSE pork. After 60 to 120 min at 42 degrees C or above, chops with pH < 5.8
      lightened until L values were similar to those typical of PSE pork (Minolta L =
      61.0). Change in chop color depended on length of time the samples were warmed,
      as well as on pH. Below 34 degrees C, temperature had no (P > or = 0.28) effect
      on color (Minolta L, a, b, and Hunter L*, a*, b*); however, at higher
      temperatures, color change depended on pH and warming time. A comparison of the
      time and temperature relationships for changes in lightness and purge suggested
      that the mechanisms of the two processes are not identical. The similarities in
      the dynamic range of color change, change in absolute color values, and time
      frame for changes in vitro and in vivo suggest similarity of the processes
      creating PSE in a carcass and in the in vitro model.

PMID- 16282624
TI  - Effect of dietary fish oil substitution with linseed oil on the performance,
      tissue fatty acid profile, metabolism, and oxidative stability of Atlantic
      salmon.
AB  - The objective of this experiment was to test the effect of total or partial
      substitution of dietary fish oil (FO) by linseed oil (LO) in Atlantic salmon
      feeding on performance, liver and muscle fatty acid composition, selected
      lipogenic and lipolytic enzyme activities, and flesh oxidative stability. For 12
      wk, fish (220 +/- 12 g of initial BW) were fed five experimental diets in which
      the FO was serially replaced by 25, 50, 75, and 100% LO. Total FO replacement by
      LO did not (P = 0.20) affect fish final weight, biometric indices, or i.m. fat
      contents. Liver and muscle neutral lipid (NL) composition responded to dietary
      treatments in different ways. Whereas the sum of n-3 PUFA in muscle followed a
      linear and quadratic pattern with increasing levels of LO, a linear (P = 0.005)
      effect was observed in the liver NL fraction. Total n-3 and n-6 PUFA contents in
      the polar lipid fraction (PL) were unaffected (P = 0.356) by dietary input of LO
      in muscle. Activity of liver glucose-6-P-dehydrogenase (G6PD) was greater with
      increasing levels of LO (P = 0.004). A time effect (P < 0.001) was observed in
      the concentration of lipid peroxidation products, expressed as thiobarbituric
      acid reactive substances, in fish flesh stored under refrigeration for 9 d;
      however, the progressive inclusion of LO in the feed did not affect (P = 0.125)
      flesh oxidation stability. In summary, LO can totally replace FO in Atlantic
      salmon feed without affecting growth performance and muscle susceptibility to
      lipid oxidation. Fatty acid metabolism in the liver was affected by LO, promoting
      G6PD activity and eicosatetraenoic acid accumulation; however, a 100% LO
      replacement decreased (P < 0.001) concentrations of eicosapentaenoic and
      docosahexaenoic acids in salmon muscle.

PMID- 16282625
TI  - Consumer sensory acceptance and value of domestic, Canadian, and Australian grass
      fed beef steaks.
AB  - To determine US consumer acceptance and value of beef from various countries, 24
      taste panels of consumers (n = 273 consumers) were conducted in Denver and
      Chicago. Two pairs of strip steaks were evaluated for flavor, juiciness,
      tenderness, and overall acceptability on eight-point hedonic scales. One pair
      consisted of an Australian grass-fed strip steak and a domestic strip steak,
      whereas the other pair included Canadian and domestic strip steaks. The pairs
      were matched to similar Warner-Bratzler shear values and marbling scores to
      decrease variation associated with tenderness and juiciness. A variation of the
      Vickery auction was used to obtain silent, sealed bids on steaks (0.45 kg) from
      the same strip loins sampled in the taste panel. Consumers gave higher (P <
      0.001) scores for flavor, juiciness, tenderness, and overall acceptability for
      domestic steaks compared with Australian grass-fed steaks. Domestic steaks
      averaged 3.68/0.45 dollars kg, whereas consumers placed an average value of
      2.48/0.45 dollars kg on Australian grass-fed steaks (P < 0.001). Consumers rated
      Canadian steaks numerically lower for juiciness (P = 0.09) and lower (P < 0.005)
      for flavor, tenderness, and overall acceptability than domestic samples.
      Consumers placed an average value of 3.95/0.45 dollars kg for domestic steaks and
      3.57/0.45 dollars kg for Canadian steaks (P < 0.01). Consumers (19.0%) who
      preferred Australian grass-fed steaks over domestic steaks paid 1.38/0.45 dollars
      kg more (P < 0.001), whereas consumers (29.3%) who favored the Canadian steaks
      over the domestic steaks paid 1.37/0.45 dollars kg more (P < 0.001) for the
      Canadian steaks. A majority of US consumers seem to be accustomed to the taste of
      domestic beef and prefer domestic steaks to beef from Australia grass-fed and
      Canadian beef.

PMID- 16282626
TI  - Beef customer satisfaction: factors affecting consumer evaluations of calcium
      chloride-injected top sirloin steaks when given instructions for preparation.
AB  - The objectives of this study were to evaluate whether instructions can help
      consumers properly prepare top sirloin steaks and to evaluate the use of calcium
      chloride injection to decrease the sensitivity of top sirloin steaks to degree of
      doneness, thereby improving customer satisfaction ratings. An in-home study
      evaluated top sirloin steaks (gluteus medius) as influenced by calcium chloride
      injection (injected vs. noninjected), consumer segment (beef loyalists = heavy
      consumers of beef, budget rotators = cost-driven and split meat consumption
      between beef and chicken, and variety rotators = higher incomes and education and
      split meat consumption among beef, poultry, and other foods), degree of doneness,
      cooking method, and instructions (given vs. not given). Consumers evaluated
      overall like, tenderness, juiciness, flavor like, and flavor amount using 10
      point scales. Beef loyalists consistently rated steaks higher for overall like,
      juiciness, and flavor when instructions were provided (P < 0.05) and rated top
      sirloin steaks higher for overall like and tenderness when given instructions for
      grilling (P < 0.05). Budget rotators and variety rotators rated steaks
      differently among cooking methods (P < 0.05). Correlation and stepwise regression
      analyses indicated that flavor like was the most highly correlated with overall
      like, followed by tenderness, flavor amount, and juiciness. Calcium chloride
      injection had no effect on consumers' likes or dislikes or on tenderness (P <
      0.05). For top sirloin steaks, it was likely that preparation played a major role
      in consumer satisfaction, and beef loyalists benefited the most from providing
      cooking instructions.

PMID- 16282627
TI  - Effects of spray-dried animal plasma and immunoglobulins on performance of early
      weaned pigs.
AB  - Five experiments were conducted to evaluate the effects of dietary spray-dried
      porcine plasma (SDPP) and spray-dried bovine plasma (SDBP) and their various
      molecular weight fractions on performance of pigs weaned at approximately 14 or
      21 d of age. In addition, the efficacy of various levels of the immunoglobulin G
      (IgG)-rich fraction of SDPP and SDBP were evaluated. Experiment 1 evaluated the
      dietary addition of SDPP and three of its fractions (IgG-rich, albumin-rich, and
      low molecular weight fractions). Pigs fed SDPP grew faster and consumed more feed
      than the controls during the first week (P < 0.05). The IgG-rich fraction
      resulted in improvements in ADG and ADFI that were similar to those of pigs fed
      SDPP. The albumin-rich fraction had no effect on growth rate, but the low
      molecular weight fraction decreased feed intake as well as growth rate.
      Experiments 2 and 3 evaluated SDPP and graded levels of its IgG-rich fraction in
      pigs weaned at 21 or 14 d, respectively. In Exp. 2, pigs fed SDPP grew faster and
      consumed more feed than the controls during the first week (P < 0.05). Pig
      performance was enhanced with the addition of the IgG-rich fraction that provided
      80% of the amount of IgG in the SDPP diet. In Exp. 3, there was no response to
      SDPP during the first week, but a positive growth response to SDPP (P < 0.01)
      occurred by the end of wk 2 (0 to 14 d). Feeding the IgG-rich fraction increased
      growth rate compared with controls (P < 0.05). Over the entire experiment, the
      greatest ADG occurred with the IgG-rich fraction that provided 128% of the amount
      of IgG provided by SDPP (quadratic; P < 0.05). Two additional experiments
      assessed feeding SDBP and bovine IgG-rich fractions to early weaned pigs. In Exp.
      4, SDPP was superior to SDBP in stimulating growth and feed intake, but this
      difference did not occur in Exp. 5. In both experiments, the IgG fraction of
      bovine plasma seemed to be as effective at improving growth as SDPP and more
      effective than SDBP. The results indicate that both porcine and bovine plasma are
      beneficial to young pig performance during the first week after weaning and that
      the IgG fraction of plasma is the component that is responsible for the
      enhancement in growth rate and feed intake.

PMID- 16282628
TI  - The effects of ractopamine hydrochloride on lean carcass yields and pork quality
      characteristics.
AB  - One hundred eighty barrows were evaluated to determine the effects of ractopamine
      hydrochloride (RAC) on lean carcass yields and pork quality. The pens were
      blocked by weight (six pens per block) with starting block weights of 69.0, 70.7,
      73.8, 76.6, 78.4, and 84.3 kg. Pens within a block were assigned randomly to one
      of three RAC treatments so each treatment in a block was replicated twice.
      Treatments (as-fed basis) included control diet, 10 ppm of RAC added (R10), and
      20 ppm of RAC added (R20) and ranged from 25 to 41 d depending on block. Pigs
      were slaughtered by blocks when block average live weights were 109 kg. Gain and
      feed efficiency were improved (P < 0.05) with increasing dietary concentrations
      of RAC, but feed intake did not differ (P > 0.05). Dressing percentage was higher
      (P < 0.05) for RAC-treated pigs. Subjective color, firmness, marbling scores, and
      Minolta L* reflection of the LM were not different (P > 0.05) among treatments.
      Carcass weights were heavier (P < 0.05) for pigs treated with RAC compared with
      control pigs and were higher for R20 than for R10. The RAC-fed pigs had greater
      (P < 0.05) yields (actual and percentage of HCW) of the following Institutional
      Meat Purchase Specification (IMPS) cuts than control pigs: trimmed, boneless ham
      (IMPS-402C and IMPS-402G), loin (IMPS-414), sirloin, and Boston butt (IMPS-406A).
      Pigs treated with RAC had a greater (P < 0.05) percentage of fat-free lean
      trimmings (IMPS-418) than did control pigs. Pigs treated with the R20
      concentration had increased (P < 0.05) water-holding capacity compared with
      control pigs. Purge loss decreased linearly (P < 0.05) with increasing RAC
      compared with control for 14-d aged, non-enhanced loins. Warner-Bratzler shear
      (WBS) force values measured for nonenhanced chops were greater for RAC-treated
      pigs than for control pigs with a low dose response (P = 0.001). Enhanced chop
      (salt and phosphate injection) WBS values did not differ (P > 0.05) among dietary
      treatments. Trained sensory evaluation panel results for tenderness decreased in
      a low-dose plateau response fashion for nonenhanced chops (P = 0.004). Tenderness
      of enhanced chops decreased linearly (P = 0.04) with increasing RAC
      concentrations. No differences (P > 0.05) were found in juiciness or flavor of
      enhanced or nonenhanced chops. Feeding RAC to late-finishing swine resulted in
      faster growing, more efficient animals with increased boneless subprimal yields,
      and it had little effect on pork juiciness and flavor.

PMID- 16282629
TI  - Effects of copper oxide bolus administration or high-level copper supplementation
      on forage utilization and copper status in beef cattle.
AB  - Two experiments were conducted to study effects of high-level Cu supplementation
      on measures of Cu status and forage utilization in beef cattle. In Exp. 1, eight
      steers randomly received an intraruminal bolus containing 12.5 g of CuO needles
      (n = 4) or no bolus (n = 4). Steers were individually offered free-choice ground
      limpograss (Hemarthria altissima) hay. On d 12 (Period 1) and d 33 (Period 2)
      steers were placed in metabolism crates, and total forage refused and feces
      produced were collected for 7 d. Daily samples of forage offered and refused and
      of feces excreted for each steer within period were analyzed for DM, ash, NDF,
      ADF, and CP. Liver biopsies were collected on d 0, 12, and 33. Copper oxide bolus
      administration resulted in greater (P < 0.03) liver Cu (DM basis) accumulation in
      Period 1 (556 vs. 296 mg/kg) and Period 2 (640 vs. 327 ppm). Apparent
      digestibilities of NDF and CP were greater (P < 0.04) for steers receiving no
      bolus in Period 2 (62.2 vs. 57.1% and 50.2 vs. 43.4% for NDF and CP
      digestibility, respectively). In Exp. 2, 24 crossbred heifers were assigned to
      individual pens and received a molasses-cottonseed meal supplement fortified with
      0, 15, 60, or 120 ppm of supplemental Cu (Cu sulfate; six pens per treatment).
      All heifers were offered free-choice access to ground stargrass (Cynodon spp.)
      hay. Heifer BW and liver biopsies were collected on d 0, 42, and 84. Forage
      refusal was determined daily, and diet DM digestibility was estimated over a 21-d
      period beginning on d 42. Heifers consuming 120 ppm of supplemental Cu gained
      less (P < 0.05; 0.04 kg/d) than heifers consuming 15 (0.19 kg/d) and 60 ppm of Cu
      (0.22 kg/d), but their ADG did not differ from that by heifers consuming no
      supplemental Cu (0.14 kg/d; pooled SEM = 0.07). Heifers supplemented with 15 ppm
      of Cu had greater (P < 0.05) liver Cu concentrations on d 84 than those on the 0
      ppm treatment and the high-Cu treatments (60 and 120 ppm). Forage intake was less
      (P = 0.07) by heifers receiving no supplemental Cu than by heifers on all other
      treatments (6.6 vs. 5.8 +/- 0.37 kg/d). Apparent forage digestibility was not
      affected by Cu treatment. These data suggest that high rates of Cu
      supplementation (Cu sulfate; > 60 ppm of total Cu) resulted in less liver Cu
      accumulation by beef heifers compared with heifers consuming diets supplemented
      with moderate dietary Cu concentrations (i.e., 15 ppm). As well, the
      administration of CuO boluses might depress the digestibility of forage nutrient
      fractions in steers.

PMID- 16282630
TI  - Reproductive characteristics of grass-fed, luteinizing hormone-releasing hormone
      immunocastrated Bos indicus bulls.
AB  - Two field trials were conducted in Brazil to evaluate LHRH immunocastration of
      Bos indicus bulls (d 0 = 2 yr of age). In Study I, 72 bulls were assigned
      randomly to one of three treatment groups: LHRH0-immunized, castrated, and
      intact. Immunized animals (n = 25) received a primary and two booster injections
      of ovalbumin-LHRH-7 and thioredoxin-LHRH-7 fusion proteins on d 0, 141, and 287.
      Twenty-three bulls were surgically castrated on d 141, and 24 served as intact
      controls. All animals were slaughtered on d 385, at approximately 3 yr of age. In
      Study II, 216 bulls were assigned randomly to the same three treatments as in
      Study I; however, because of a drought in the area, bulls were kept on pasture an
      additional year, and a fourth treatment was added, in which one-half the LHRH
      immunized bulls received an additional booster on d 639 (fourth immunization).
      All animals in Study II were slaughtered on d 741 (4 yr of age). Luteinizing
      hormone-releasing hormone antibodies increased following each immunization for
      immunized bulls, but they were not detectable in castrate or intact animals in
      either study. Consequently, scrotal circumference was suppressed in immunized
      bulls compared with intact controls in both studies. By d 287, serum
      concentrations of testosterone in LHRH-immunized bulls were decreased compared
      with intact controls (P < 0.01). In both studies, testes and epididymal weights
      at slaughter were greater (P < 0.01) for intact (500 +/- 17 and 60 +/- 2 g,
      respectively) than for immunized bulls (173 +/- 22 and 26 +/- 2 g, respectively)
      and fourth immunization bulls (78 +/- 23 and 20 +/- 2 g, respectively; Study II).
      At the end of each study, BW was greater (P < 0.01) for intact bulls than for
      castrated and LHRH-immunized animals. In these two studies, the efficacy of the
      LHRH fusion proteins to induce an effect similar to that of surgical castration
      was considered 92 and 93%, respectively. These data support the concept that
      immunocastration of bulls at 2 yr of age was successful and that it has practical
      application as a tool for producing grass-fattened bulls in Brazil.

PMID- 16282631
TI  - Body condition score at parturition and postpartum supplemental fat effects on
      cow and calf performance.
AB  - Three-year-old Angus x Gelbvieh beef cows nutritionally managed to achieve a BCS
      of 4 +/- 0.07 (479.3 +/- 36.3 kg of BW) or 6 +/- 0.07 (579.6 +/- 53.1 kg of BW)
      at parturition were used in a 2-yr experiment (n = 36/yr) to determine the
      effects of prepartum energy balance and postpartum lipid supplementation on cow
      and calf performance. Beginning 3 d postpartum, cows within each BCS were
      assigned randomly to be fed hay and a low-fat control supplement or supplements
      with either high-linoleate cracked safflower seeds or high-oleate cracked
      safflower seeds until d 60 of lactation. Diets were formulated to be
      isonitrogenous and isocaloric, and safflower seed supplements were provided to
      achieve 5% of DMI as fat. Ultrasonic 12th rib fat and LM area were lower (P <
      0.001) for cows in BCS 4 compared with BCS 6 cows throughout the study. Cows in
      BCS 4 at parturition maintained (P = 0.02) condition over the course of the
      study, whereas cows in BCS 6 lost condition. No differences (P = 0.44 to 0.71)
      were detected for milk yield, milk energy, milk fat percentage, or milk lactose
      percentage because of BCS; however, milk protein percentage was less (P = 0.03)
      for BCS 4 cows. First-service conception rates did not differ (P = 0.22) because
      of BCS at parturition, but overall pregnancy rate was greater (P = 0.02) in BCS 6
      cows. No differences (P = 0.48 to 0.83) were detected in calf birth weight or ADG
      because of BCS at parturition. Dietary lipid supplementation did not influence (P
      = 0.23 to 0.96) cow BW change, BCS change, 12th rib fat, LM area, milk yield,
      milk energy, milk fat percentage, milk lactose percentage, first service
      conception, overall pregnancy rates, or calf performance. Although cows in BCS of
      4 at parturition seemed capable of maintaining BCS during lactation, the overall
      decrease in pregnancy rate indicates cows should be managed to achieve a BCS >4
      before parturition to improve reproductive success.

PMID- 16282632
TI  - Factors affecting carcass value and profitability in early-weaned Simmental
      steers: I. Five-year average pricing.
AB  - In a 4-yr study, early-weaned Simmental steers (n = 192) of known genetics were
      individually fed to determine genetic, performance, and carcass factors
      explaining variation in carcass value and profitability. Steers were weaned at
      88.0 +/- 1.1 d of age and pen-fed a high-concentrate diet (108.99 dollars/t) for
      84.5 +/- 0.4 d before allotment. Calves were implanted with Synovex C at weaning
      and successively with Synovex S (Fort Dodge Animal Health, Fort Dodge, IA) and
      Revalor S (Intervet, Inc., Millsboro, DE). Steers consumed a 90% concentrate diet
      (98.93 dollars/t), consisting primarily of coarse cracked corn and corn silage,
      for 249.7 +/- 0.7 d and slaughtered at 423.3 +/- 1.4 d of age. Five-year price
      data were collected for feedstuffs, dressed beef, and grid premiums, and
      discounts. Average dressed beef price was 110.67 dollars/45.4 kg. Premiums
      (dollars/45.4 kg) were given for Prime (5.62 dollars), Average Choice (1.50
      dollars), and yield grades (YG) 1 (2.46 dollars), 2A (1.31 dollars), and 2B (1.11
      dollars). Discounts (dollars/45.4 kg) were given for Standard (-16.85 dollars),
      Select (-8.90 dollars), and YG 3A (-0.12 dollars), 3B (-0.19 dollars), 4 (-14.16
      dollars), and 5 (-19.56 dollars). Discounts were given for HCW extremes as well
      (409 to 431 kg, -0.64 dollars; 432 to 454 kg -11.39 dollars; > 454 kg, -19.71
      dollars). Input costs included annual cow costs (327.77 dollars),
      veterinary/medical and labor (35 dollars per animal), feed markup (22 dollars/t),
      yardage (0.25 dollars/d per animal), and interest (10%). Dependent variables were
      carcass value and profit per steer. Independent variables were year, weaning
      weight EPD, yearling weight EPD, marbling EPD, DMI, ADG, G:F, HCW, calculated YG,
      and marbling score (MS). Carcass value was correlated (P < 0.05) with yearling
      weight and marbling EPD, DMI, ADG, feed efficiency, HCW, and MS. Carcass weight,
      MS, and YG accounted for nearly 80% of the variation in carcass value among
      steers, explaining 51, 10, and 8%, respectively. Profit was correlated (P < 0.05)
      with DMI, ADG, feed efficiency, HCW, and MS. Carcass weight, MS, YG, and DMI
      accounted for nearly 78% of the variation in profit among steers, explaining 21,
      18, 12, and 3%, respectively. Carcass weight was the most critical factor
      contributing to carcass value, whereas BW and carcass quality were the primary
      factors affecting steer profitability. These models represent the relative
      importance of factors contributing to value and profitability in early-weaned
      Simmental steers based on historical pricing scenarios.

PMID- 16282633
TI  - Factors affecting carcass value and profitability in early-weaned Simmental
      steers: II. Days on feed endpoints and sorting strategies.
AB  - In a 4-yr study, early-weaned Simmental steers (n = 192) of known genetics were
      individually fed to determine EPD, performance, and carcass measurements
      explaining variation in carcass value and profitability across incremental days
      on feed (DOF) when sorted by HCW, calculated yield grade (YG), or at their
      highest profit endpoint (BEST). Steers were weaned at 88.0 +/- 1.1 d of age, pen
      fed a high-concentrate diet for 84.5 +/- 0.4 d, individually fed for 249.7 +/-
      0.7 d, and slaughtered at 423.3 +/- 1.4 d of age. Carcass weight, YG, and
      marbling score (MS) were predicted using real-time ultrasound throughout the
      finishing period to calculate carcass value and profitability at 90, 60, 30 d
      preslaughter and under three individual sorting strategies. Sorting strategies
      included marketing the 25 and 50% heaviest HCW, the highest YG at d 60 and 30, or
      the remaining 25% at 0-d endpoints. Independent variables were year, weaning
      weight EPD, yearling weight EPD, marbling EPD, DMI, ADG, HCW, YG, and MS. Profit
      was quadratic in response to increased DOF; the greatest economic return was
      noted on d 30 (pre-slaughter). Final weight, DMI, HCW, MS, and YG increased
      (linear; P < 0.001) with additional DOF, and ADG and G:F decreased (linear; P <
      0.001). Total cost of gain was quadratic (P < 0.001), and incremental cost of
      gain rose at an increasing rate (quadratic; P < 0.001) with increased DOF. With
      increasing DOF, HCW importance decreased from 58 to 21%; MS was variable, ranging
      from 18 to 23%; and YG and DMI were minor contributors to profit variation. Among
      sorting strategies, final BW and HCW were greater for BEST, whereas other
      measurements were similar. Sorting individuals by HCW, YG, or at BEST increased
      profitability 3.70 dollars, 2.52 dollars, or 30.65 dollars over the optimal group
      DOF endpoint (d 30). Retrospective analyses illustrated that sorting does not
      need to pinpoint each animal's profit optimum to result in economic gains;
      rather, increasing HCW and decreasing weight- and YG-related penalties improved
      profitability. Opportunities may exist with existing and new technology to
      uniformly allocate cattle into feeding and marketing groups, decrease
      overfeeding, and increase carcass value and profitability.

PMID- 16282634
TI  - Effects of cooked molasses blocks and fermentation extract or brown seaweed meal
      inclusion on intake, digestion, and microbial efficiency in steers fed low
      quality hay.
AB  - Five ruminally, duodenally, and ileally cannulated steers (376 +/- 8.1 kg of
      initial BW) were used in a 5 x 5 Latin square to evaluate effects of cooked
      molasses block supplementation and inclusion of fermentation extract (Aspergillus
      oryzae) or brown seaweed meal (Ascophyllum nodosum) on intake, site of digestion,
      and microbial efficiency. Diets consisted of switchgrass hay (6.0% CP; DM basis)
      offered ad libitum, free access to water, and one of three molasses blocks (0.341
      kg of DM/d; one-half at 0600 and one-half at 1800). Treatments were no block
      (control), block with no additive (40.5% CP; POS), block plus fermentation
      extract bolused directly into the rumen via gelatin capsules (2.0 g/d; FS),
      fermentation extract included in the block (2.0 g/d; FB), and seaweed meal
      included in the block (10 g/d; SB). Steers were adapted to diets for 14 d
      followed by a 7-d collection period. Overall treatment effect on hay OM intake
      tended (8.1 vs. 7.6 +/- 0.5 kg/d; P = 0.14) to increase with block
      supplementation. Total OM intake (8.4 vs. 7.6 +/- 0.5 kg/d; P = 0.01) increased
      in steers consuming block compared with control. Apparent and true ruminal OM
      digestibility increased (P = 0.05) with block consumption. Steers fed SB had
      greater (P = 0.10) true ruminal OM digestibility compared with steers fed POS
      (61.0 vs. 57.9 +/- 1.6%). True ruminal CP digestibility increased (P = 0.01) with
      block supplementation compared with control (37.5 vs. 23.6 +/- 3.7%). Addition of
      fermentation extract did not affect intake or digestion. Treatments did not alter
      ruminal pH, total VFA, or individual VFA proportions; however, ruminal ammonia
      increased (P = 0.01) with block supplementation. In situ disappearance rates of
      hay DM (3.14 +/- 0.44 %/h), NDF (3.18 +/- 0.47 %/h), and ADF (3.02 +/- 0.57 %/h)
      were not altered by treatment. Seaweed block increased (P = 0.01) slowly degraded
      CP fraction compared with POS (39.5 vs. 34.0 +/- 2.07%). Similarly, SB increased
      (P = 0.01) the extent of CP degradability (74.2 vs. 68.9 +/- 1.81%). No treatment
      effects (P = 0.24) were observed for microbial efficiency. Block supplementation
      increased intake, and use of brown seaweed meal seemed to have beneficial effects
      on forage digestibility in low-quality forage diets.

PMID- 16282635
TI  - Evaluation of "subject advocate" procedures in the Clinical Antipsychotic Trials
      of Intervention Effectiveness (CATIE) schizophrenia study.
AB  - Because the decision-making capacity of individuals with schizophrenia may
      fluctuate, additional protections for such persons who enroll in long-term
      research studies may be needed. For the NIMH-sponsored Clinical Antipsychotic
      Trials of Intervention Effectiveness (CATIE) schizophrenia study, new procedures
      were developed to help ensure an objective assessment of a patient's continued
      participation in the study if decision-making capacity lapsed. Each research
      participant had a subject advocate who could recommend that the subject be
      withdrawn from the study if capacity lapsed and continued participation was not
      in the subject's best interest. The main goals of the procedures were to protect
      the interests of subjects and to prevent unnecessary dropouts. We surveyed
      research personnel regarding the effectiveness and implementation of the
      procedures. Responses were received from 73 personnel at 49 research sites,
      representing 70% of possible respondents and 91% of eligible sites. A majority of
      respondents were favorably disposed toward subject advocates, and though most
      reported that the procedures had no discernible effect on study recruitment,
      subject autonomy, or subject retention, for those who reported an impact, it was
      almost always positive. Some respondents reported that the procedures helped by
      engaging family members and promoting a positive view of schizophrenia research.
      A majority thought that similar arrangements would be useful in future
      longitudinal research studies. Nonspecific benefits included good public
      relations and engagement of family members. Improved training regarding the
      procedures may be needed to achieve specific goals of enhanced patient autonomy
      and retention in the study.

PMID- 16282636
TI  - Personal account: snapshots: the first symptoms of psychosis.

PMID- 16282638
TI  - Mutation of F417 but not of L418 or L420 in the lipid binding domain decreases
      the activity of triacylglycerol hydrolase.
AB  - Human triacylglycerol hydrolase (hTGH) has been shown to play a role in hepatic
      lipid metabolism. Triacylglycerol hydrolase (TGH) hydrolyzes insoluble carboxylic
      esters at lipid/water interfaces, although the mechanism by which the enzyme
      adsorbs to lipid droplets is unclear. Three-dimensional modeling of hTGH predicts
      that catalytic residues are adjacent to an alpha-helix that may mediate TGH/lipid
      interaction. The helix contains a putative neutral lipid binding domain
      consisting of the octapeptide FLDLIADV (amino acid residues 417-424) with the
      consensus sequence FLXLXXXn (where n is a nonpolar residue and X is any amino
      acid except proline) identified in several other proteins that bind or metabolize
      neutral lipids. Deletion of this alpha-helix abolished the lipolytic activity of
      hTGH. Replacement of F417 with alanine reduced activity by 40% toward both
      insoluble and soluble esters, whereas replacement of L418 and L420 with alanine
      did not. Another potential mechanism of increasing TGH affinity for lipid is via
      reversible acylation. Molecular modeling predicts that C390 is available for
      covalent acylation. However, neither chemical modification of C390 nor mutation
      to alanine affected activity. Our findings indicate that F417 but not L418, L420,
      or C390 participates in substrate hydrolysis by hTGH.

PMID- 16282639
TI  - Human apoA-I expression in CETP transgenic rats leads to lower levels of apoC-I
      in HDL and to magnification of CETP-mediated lipoprotein changes.
AB  - Plasma cholesteryl ester transfer protein (CETP) has a profound effect on neutral
      lipid transfers between HDLs and apolipoprotein B (apoB)-containing lipoproteins
      when it is expressed in combination with human apoA-I in HuAI/CETP transgenic
      (Tg) rodents. In the present study, human apoA-I-mediated lipoprotein changes in
      HuAI/CETPTg rats are characterized by 3- to 5-fold increments in the apoB
      containing lipoprotein-to-HDL cholesterol ratio, and in the cholesteryl ester-to
      triglyceride ratio in apoB-containing lipoproteins. These changes occur despite
      no change in plasma CETP concentration in HuAI/CETPTg rats, as compared with
      CETPTg rats. A number of HDL apolipoproteins, including rat apoA-I and rat apoC-I
      are removed from the HDL surface as a result of human apoA-I overexpression. Rat
      apoC-I, which is known to constitute a potent inhibitor of CETP, accounts for
      approximately two-thirds of CETP inhibitory activity in HDL from wild-type rats,
      and the remainder is carried by other HDL-bound apolipoprotein inhibitors. It is
      concluded that human apoA-I overexpression modifies HDL particles in a way that
      suppresses their ability to inhibit CETP. An apoC-I decrease in HDL of
      HuAI/CETPTg rats contributes chiefly to the loss of the CETP-inhibitory potential
      that is normally associated with wild-type HDL.

PMID- 16282637
TI  - Ethical concerns in schizophrenia research: looking back and moving forward.

PMID- 16282640
TI  - PPARalpha activation increases triglyceride mass and adipose differentiation
      related protein in hepatocytes.
AB  - Adipose differentiation-related protein (ADRP) is a lipid droplet-associated
      protein that is expressed in various tissues. In mice treated with the peroxisome
      proliferator-activated receptor alpha (PPARalpha) agonist Wy14,643 (Wy), hepatic
      mRNA and protein levels of ADRP as well as hepatic triglyceride content
      increased. Also in primary mouse hepatocytes, Wy increased ADRP expression and
      intracellular triglyceride mass. The triglyceride mass increased in spite of
      unchanged triglyceride biosynthesis and increased palmitic acid oxidation.
      However, Wy incubation decreased the secretion of newly synthesized
      triglycerides, whereas apolipoprotein B secretion increased. Thus, decreased
      availability of triglycerides for VLDL assembly could help to explain the
      cellular accumulation of triglycerides after Wy treatment. We hypothesized that
      this effect could be mediated by increased ADRP expression. Similar to PPARalpha
      activation, adenovirus-mediated ADRP overexpression in mouse hepatocytes enhanced
      cellular triglyceride mass and decreased the secretion of newly synthesized
      triglycerides. In ADRP-overexpressing cells, Wy incubation resulted in a further
      decrease in triglyceride secretion. This effect of Wy was not attributable to
      decreased cellular triglycerides after increased fatty acid oxidation because the
      triglyceride mass in Wy-treated ADRP-overexpressing cells was unchanged. In
      summary, PPARalpha activation prevents the availability of triglycerides for VLDL
      assembly and increases hepatic triglyceride content in part by increasing the
      expression of ADRP.

PMID- 16282641
TI  - European recommendations for the management of healthcare workers occupationally
      exposed to hepatitis B virus and hepatitis C virus.
AB  - Exposure prevention is the primary strategy to reduce the risk of occupational
      bloodborne pathogen infections in healthcare workers (HCW). HCWs should be made
      aware of the medicolegal and clinical relevance of reporting an exposure, and
      have ready access to expert consultants to receive appropriate counselling,
      treatment and follow-up. Vaccination against hepatitis B virus (HBV), and
      demonstration of immunisation before employment are strongly recommended. HCWs
      with postvaccinal anti-HBs levels, 1-2 months after vaccine completion, >or=10
      mIU/mL are considered as responders. Responders are protected against HBV
      infection: booster doses of vaccine or periodic antibody concentration testing
      are not recommended. Alternative strategies to overcome non-response should be
      adopted. Isolated anti-HBc positive HCWs should be tested for anti-HBc IgM and
      HBV-DNA: if negative, anti-HBs response to vaccination can distinguish between
      infection (anti-HBs >or=50 mUI/ml 30 days after 1st vaccination: anamnestic
      response) and false positive results(anti-HBs >or=10 mUI/ml 30 days after 3rd
      vaccination: primary response); true positive subjects have resistance to re
      infection. and do not need vaccination The management of an occupational exposure
      to HBV differs according to the susceptibility of the exposed HCW and the
      serostatus of the source. When indicated, post-exposure prophylaxis with HBV
      vaccine, hepatitis B immunoglobulin or both must be started as soon as possible
      (within 1-7 days). In the absence of prophylaxis against hepatitis C virus (HCV)
      infection, follow-up management of HCV exposures depends on whether antiviral
      treatment during the acute phase is chosen. Test the HCW for HCV-Ab at baseline
      and after 6 months; up to 12 for HIV-HCV co-infected sources. If treatment is
      recommended, perform ALT (amino alanine transferase) activity at baseline and
      monthly for 4 months after exposure, and qualitative HCV-RNA when an increase is
      detected.

PMID- 16282642
TI  - Surveillance of listeria infections in Europe.
AB  - In addition to the economic consequences and threats associated with outbreaks,
      listeriosis remains of great public health concern, as it has one of the highest
      case fatality rates of all the foodborne infections (20%-30%), and has common
      source epidemic potential. Changes in the way food is produced, distributed and
      stored have created the potential for diffuse and widespread outbreaks involving
      many countries. In 2002, a survey was carried out to assess the need for and the
      feasibility of a European network on listeria infections in humans. Data on
      surveillance systems and laboratory methods were collected through two postal
      surveys sent to the national Centres for communicable disease surveillance and to
      the listeria reference laboratories. Surveillance systems for listeria infections
      were in operation in 16 out of the 17 countries surveyed, and 16 countries had a
      national reference laboratory (NRL). All countries based their case definition of
      listeriosis on the isolation of Listeria monocytogenes. Fourteen NRLs performed
      at least one typing method on human strains. At least 13 countries already
      carried out or expressed willingness to carry out characterisation of isolates by
      pulsed field gel electrophoresis (PFGE) of L. monocytogenes strains isolated from
      human cases following a standard protocol. The participants concluded that there
      was a clear added value to having a European surveillance network for listeria
      infections, particularly for outbreak detection and investigation, and that a
      surveillance network based on the existing national surveillance systems was
      feasible.

PMID- 16282643
TI  - Late detection of a shigellosis outbreak in a school in Madrid.
AB  - Even though shigellosis in Spain is rare, an indigenous outbreak is occasionally
      detected. We describe an outbreak in a school in Madrid caused by person-to
      person transmission of Shigella sonnei. After the detection of Shigella sonnei in
      a stool sample from a 3 year old girl, an investigation at her school was
      initiated. Questionnaires were distributed to the parents of 520 pupils attending
      the school. A case was defined as a school case if it was the first case in a
      child's household, and as a household case if other members of the household had
      fallen ill first. We identified 88 cases (60 pupils and 28 of their family
      members). The attack rate (AR) was 12% in the school and 32% in the families.
      There was a significant association between higher AR and lower age. The outbreak
      lasted for two months. The length and the shape of the epidemic curve of the 60
      cases in pupils suggests person-to-person transmission. Shigella sonnei isolated
      from 5 different cases were typed by pulsed field gel electrophoresis (PFGE) and
      was found to be an identical strain. The prolonged duration of the outbreak was
      probably due to delayed detection, and stopped as soon as control measures were
      introduced.

PMID- 16282644
TI  - Completeness of malaria notification in the Netherlands 1995-2003 assessed by
      capture-recapture method.
AB  - In 1999 in the Netherlands, the duty to notify malaria was transferred from
      physicians to laboratories by the new Infectious Diseases Law. To evaluate the
      effect of this change, we aimed to estimate completeness of malaria notification
      in the Netherlands from 1995-2003. We calculated it relative to sentinel
      laboratory and hospital admission data. Using the two-source capture-recapture
      method (CRM), we estimated the total number of cases to assess the completeness
      relative to this number. The completeness of notification relative to sentinel
      data was 18.2 % (95% CI of 15.7-20.7) from 1995-1998 and 56.4 % (95% CI of 47.0
      65.8) for 2000-2003. The completeness relative to the number of malaria cases
      admitted to the hospital was 35.1 % for the period 1995-2003. The estimated
      numbers of cases of malaria between 1995 and 1998 were 3123 (95% CI of 2796-3449)
      and 5043 (95% CI of 4343-5742) between 2000 and 2003. The completeness relative
      to this numbers changed from 35.5 % (95% CI of 32.1-39.7) in 1995-1998 to 36.1 %
      (95% CI of 31.7-41.9) for the years 2000-2003. Laboratory-based notification has
      significantly increased the absolute number of malaria notifications, but there
      was no change in completeness relative to hospital admissions. The increase in
      estimated malaria cases may be artificial, due to the extent of violation of CRM
      requirements over the study period.

PMID- 16282645
TI  - New diagnoses of HTLV infection in England and Wales: 2002-2004.
AB  - Human T cell lymphotropic viruses (HTLV) are retroviruses transmitted through
      breastfeeding, sexual contact, blood transfusion and injecting drug use. HTLV is
      endemic in the Caribbean, and parts of Africa, Japan and South America, with
      isolated foci in other areas. Infection is life long. Fewer than 5% of those
      infected progress to one of the HTLV-related diseases, but these are debilitating
      and often fatal. In England and Wales, laboratory and clinical reports of new
      HTLV diagnoses are routinely collected, including infections identified by the
      blood service since the introduction of anti-HTLV testing in August 2002. Between
      2002 and 2004, 273 individuals were diagnosed with HTLV: 102 (37%) were male and
      169 female (sex was not reported for two). Median ages at diagnosis were 54 and
      50 years respectively. Clinical reports were received for 78% (212/273)
      individuals. Where reported, 58% (116/199) of individuals were of black Caribbean
      ethnicity and 29% (57/199) white; 87% (128/147) were probably infected
      heterosexually or through mother-to-child transmission; 45% (66/146) were
      probably infected in the Caribbean and 40% (59/146) in the United Kingdom. An
      appreciable number of HTLV infections continue to be diagnosed within England and
      Wales, with increases in 2002-2003 because of anti-HTLV testing of blood
      donations. While most infections diagnosed are directly associated with the
      Caribbean, transmission of HTLV infection is occurring within England and Wales.
      Specialist care services for HTLV-infected individuals and their families have
      improved in recent years, but prevention remains limited.

PMID- 16282647
TI  - Smart personalised health systems: from gadgets to better health.

PMID- 16282646
TI  - Disseminated and chronic Lyme borreliosis in Norway, 1995 - 2004.
AB  - Lyme borreliosis is the most common tickborne infection in Norway. All clinical
      manifestations of Lyme borreliosis other than erythema migrans are notifiable to
      Folkehelseinstituttet, the Norwegian Institute of Public Health. During the
      period 1995-2004 a total of 1506 cases of disseminated and chronic Lyme
      borreliosis were reported. Serological tests were the basis for laboratory
      diagnosis in almost all cases. The annual numbers of cases showed no clear trend
      over the period, but varied each year between 120 and 253 cases, with the highest
      number of cases reported in 2004. Seventy five per cent of cases with information
      on time of onset were in patients who fell ill during the months of June to
      October. There was marked geographical variation in reported incidence rates,
      with the highest rates reported from coastal counties in southern and central
      Norway. Fifty six per cent of the cases were in males and 44% in females. The
      highest incidence rate was found in children aged between 5 and 9 years.
      Neuroborreliosis was the most common clinical manifestation (71%), followed by
      arthritis/arthralgia (22%) and acrodermatitis chronica atrophicans (5%). Forty
      six per cent of patients were admitted to hospital. Prevention of borreliosis in
      Norway relies on measures to prevent tick bites, such as use of protective
      clothing and insect repellents, and early detection and removal of ticks.
      Antibiotics are generally not recommended for prophylaxis after tick bites in
      Norway.

PMID- 16282648
TI  - Wearable healthcare systems, new frontiers of e-textile.
AB  - There is a growing need of renovation in our health care managing systems; people
      need to be more interactive and more conscious of their own health condition in a
      way to adjust incorrect lifestyles, to obtain a personalized therapy tuned to
      their own physiological reactions and on their own environmental condition. To
      gain knowledge of a citizen's health status and to monitor without harassing them
      (until they refuse any medical supervision), a comfortable remote monitoring of
      important physiological parameters is necessary. The approach is therefore to
      integrate system solutions into functional clothes with integrated textile
      sensors. The combination of functional clothes and integrated electronics and on
      body processing, is defined as e-textile and gives rise to intelligent biomedical
      clothes. Systems, designed to be minimally invasive, are based on smart textile
      technologies, where conductive and piezoresistive materials in the form of fiber
      and yarn are used to realize clothes, in which knitted fabric sensors and
      electrodes are distributed and connected to an electronic portable unit. These
      systems are able to detect, acquire and transmit physiological signals. They are
      conformable to the human body, and move towards improving the patient's quality
      of life and their autonomy. These systems are also cost-effective in providing
      around-the-clock assistance, in helping physicians to monitor for example cardiac
      patients during periods of rehabilitation, and in addition result in decreased
      hospitalization time. Finally, by providing direct feedback to the users, they
      improve their awareness and potentially allow better control of their own
      condition, while the simultaneous recording of vital signs permits parameter
      extrapolation and inter-signal elaboration that contributes to produce alert
      messages and personalized synoptic tables of the patient's health.

PMID- 16282649
TI  - Electroactive fabrics for distributed, comfortable and interactive systems.
AB  - Monitoring body kinematics has fundamental relevance in several biological and
      technical disciplines. In particular the possibility to know the posture exactly
      may furnish a main aid in rehabilitation topics. In the present work a collection
      of innovative and unobtrusive garments able to detect the posture and the
      movement of the human body are introduced. This paper deals with the design, the
      development and the realization of sensing garments, from the characterization of
      innovative comfortable and spreadable sensors to the methodologies employed to
      gather information on the posture and movement. Several new algorithms devoted to
      the device operation are presented and tested. Data derived from the sensing
      garment are analyzed and compared with the data derived from a traditional
      movement tracking system.

PMID- 16282650
TI  - Point of care biomedical sensors.
AB  - With the development of critical areas of interdisciplinary research, scientists
      will lead to an enhanced understanding and control of the key processing stages
      involved in the design and manufacture of sensor-and electrode-based micro
      devices such as micro total analysis systems (muTAS), bio-chips, bio-arrays and
      DNA sensors. It is anticipated that this fundamental work will lead to tangible
      technology transfer in the areas of blood analysis, cardiac enzyme detectors,
      liver and renal function, infectious diseases, gene disorders, etc. These will
      obviously have major benefits to healthcare delivery. The development of
      miniaturised, integrated sensor/electrode-based devices are revolutionising both
      the delivery of health care. In this paper, some of the most exciting research
      themes in these areas are identified, as well as novel underpinning fabrication
      technologies and transduction principles, which should make future advances
      possible.

PMID- 16282651
TI  - Bioimpedance and p-Health.
AB  - Bio-impedance is the electrical impedance of living matter. Bio-impedance methods
      present a range of known advantages for medical and clinical applications
      including low-cost, non-invasiveness and harmlessness. The measured parameter
      reflects the physiological and pathological processes that take place within
      human body. The technological progress in instrumentation has significantly
      contributed to the progress that has been observed during the last past decades
      in impedance spectroscopy and electrical impedance tomography. Although
      bioimpedance is not a physiological parameter, the method enables tissue
      characterisation and functional monitoring and can contribute to the monitoring
      of the health status of a person. The association of this flexible and versatile
      method with micro-electronics and wireless telecommunication systems opens a new
      field of potential applications.

PMID- 16282652
TI  - Vital sign monitoring for elderly at home: development of a compound sensor for
      pulse rate and motion.
AB  - This paper describes the development of a miniaturized wearable vital sign
      monitor which is aimed for use by elderly at home. The development of a compound
      sensor for pulse rate, motion, and skin temperature is reported. A pair of
      infrared sensor working in reflection mode was used to detect the pulse rate from
      various sites over the body including the wrist and finger. Meanwhile, a motion
      sensor was used to detect the motion of the body. In addition, the temperature on
      the skin surface was sensed by a semiconductor temperature sensor. A prototype
      has been built into a box with a dimension of 2 x 2.5 x 4 cm3. The device
      includes the sensors, microprocessor, circuits, battery, and a wireless
      transceiver for communicating data with a data terminal.

PMID- 16282653
TI  - MyHeart: fighting cardio-vascular diseases by preventive lifestyle and early
      diagnosis.
AB  - Cardio-vascular diseases (CVD) are the leading cause of death. The MyHeart
      Project aims at empowering the citizens to fight cardio-vascular diseases by
      preventive lifestyle and early diagnosis. The main technical challenges in this
      project are the combination of novel wearable technologies (novel textile and
      electronic sensors, personalised algorithms, on-body computing) and user feedback
      and motivation concepts, in order to make a breakthrough towards new applications
      for prevention and early diagnose possible.

PMID- 16282654
TI  - Motion aware clothing for the personal health assistant.
AB  - This paper sketches the vision and first results of a 'Personal Health Assistant'
      PHA, opening up new vistas in patient centred healthcare. The PHA is comprised of
      a wearable sensing and communicating system, seamlessly embedded in daily
      clothing. Several on-body sensors monitor the biometric and contextual status of
      the wearer continuously. The embedded computer fuses the vital and physiological
      data with activity patterns of the wearer and with the social environment; based
      on these data the on-body computer generates the 'Life Balance Factor' LBF as an
      individual feedback to the user and to the surroundings afford-ing effective
      disease prevention, management and rehabilitation, the last also involving
      telemedicine. The state-of-the-art enabling technologies: smart textile
      technology and miniaturization of electronics combined with wireless
      communication, along with recent developments in wearable computing are presented
      and assessed in the context of multiparameter health monitoring.

PMID- 16282655
TI  - Integrated microelectronics for smart textiles.
AB  - The combination of textile fabrics with microelectronics will lead to completely
      new applications, thus achieving elements of ambient intelligence. The
      integration of sensor or actuator networks, using fabrics with conductive fibres
      as a textile motherboard enable the fabrication of large active areas. In this
      paper we describe an integration technology for the fabrication of a "smart
      textile" based on a wired peer-to-peer network of microcontrollers with
      integrated sensors or actuators. A self-organizing and fault-tolerant
      architecture is accomplished which detects the physical shape of the network.
      Routing paths are formed for data transmission, automatically circumventing
      defective or missing areas. The network architecture allows the smart textiles to
      be produced by reel-to-reel processes, cut into arbitrary shapes subsequently and
      implemented in systems at low installation costs. The possible applications are
      manifold, ranging from alarm systems to intelligent guidance systems, passenger
      recognition in car seats, air conditioning control in interior lining and smart
      wallpaper with software-defined light switches.

PMID- 16282656
TI  - Wearable Sensors? What is there to sense?
AB  - This paper provides an overview of research conducted in the development of
      ambulatory devices for wearable sensing applications. Two configurations of
      wearable sensing are shown, the first a wearable chemosensor in a wrist-watch
      configuration, and the second a textile with an integrated foam sensor. The foam
      sensor is composed of polypyrrole-coated polyurethane foam, which exhibits a
      piezo-resistive response when exposed to electrical current. The potential of
      wearable sensing is discussed using these examples to illustrate the relevant
      concerns.

PMID- 16282657
TI  - Micro and nano technology enabling ambient intelligence for P-Health.
AB  - This chapter will discuss the ongoing development and integration of micro and
      nano technologies within the Tyndall National Institute that will enable the
      future vision of ambient intelligence with specific application to the area of
      personalised health (P-Health). Ambient Intelligent Systems open entirely new
      possibilities for future applications and resultant markets. Ultimately, these
      systems will create intelligent environments that cater continuously for the
      requirements of the individual in everyday life and apply it in a totally
      coherent manner. They will learn and evolve to anticipate user-requirements. We
      will discuss ongoing research in the areas of sensors, sensor interfacing,
      interconnection and packaging, hardware platforms, infrastructure and power
      delivery for ambient systems with applications in the p-health domain.

PMID- 16282658
TI  - A small step for science, a big one for commerce.
AB  - The excellent work that is being performed in medical science advances is to be
      admired and applauded. In each case the quest is for perfection and to bring the
      task in hand to its final solution. Along the way there are milestones being
      passed that may be overlooked, as to their particular merits, because the eyes
      are focused all the time on the ultimate goal. The conference highlights so many
      areas of interest and endeavour some of which parallel, duplicate, overlap and/or
      compliment others.

PMID- 16282659
TI  - The efficacy of knowledge management for personalised healthcare.
AB  - This chapter examines some of the key issues surrounding the incorporation of the
      Knowledge Management (KM) paradigm for personalised healthcare. We discuss the
      complex nature of KM, some essential concepts necessary to make personalised
      healthcare a reality and introduce a schematic which illustrates the efficacy of
      KM for personalised health.

PMID- 16282660
TI  - Interoperability as a quality label for portable & wearable health monitoring
      systems.
AB  - Advances in ICT promising universal access to high quality care, reduction of
      medical errors, and containment of health care costs, have renewed interest in
      electronic health records (EHR) standards and resulted in comprehensive EHR
      adoption programs in many European states. Health cards, and in particular the
      European health insurance card, present an opportunity for instant cross-border
      access to emergency health data including allergies, medication, even a reference
      ECG. At the same time, research and development in miniaturized medical devices
      and wearable medical sensors promise continuous health monitoring in a
      comfortable, flexible, and fashionable way. These trends call for the seamless
      integration of medical devices and intelligent wearables into an active EHR
      exploiting the vast information available to increase medical knowledge and
      establish personal wellness profiles. In a mobile connected world with empowered
      health consumers and fading barriers between health and healthcare,
      interoperability has a strong impact on consumer trust. As a result, current
      interoperability initiatives are extending the traditional standardization
      process to embrace implementation, validation, and conformance testing. In this
      paper, starting from the OpenECG initiative, which promotes the consistent
      implementation of interoperability standards in electrocardiography and supports
      a worldwide community with data sets, open source tools, specifications, and
      online conformance testing, we discuss EHR interoperability as a quality label
      for personalized health monitoring systems. Such a quality label would support
      big players and small enterprises in creating interoperable eHealth products,
      while opening the way for pervasive healthcare and the take-up of the eHealth
      market.

PMID- 16282661
TI  - Software process improvement for the medical industry.
AB  - This chapter describes a software process improvement framework, structured to
      ensure regulatory compliance for the software developed in medical devices.
      Software is becoming an increasingly important aspect of medical devices and
      medical device regulation. Medical devices can only be marketed if compliance and
      approval from the appropriate regulatory bodies of the Food and Drug
      Administration (US requirement), and the European Commission under its Medical
      Device Directives (CE marking requirement) is achieved.

PMID- 16282662
TI  - Interoperability--a key infrastructure requirement for personalised health
      services.
AB  - Functional and semantic interoperability requirements for ubiquitous personalised
      health services reach beyond current concepts of health information integration
      among professional stakeholders and related Electronic Patient Records
      ("eHealth"): Future health telematics infrastructures have particularly to
      maintain semantic interoperability among systems using different coding schemes
      and terminologies and to include home, personal and mobile systems.

PMID- 16282663
TI  - Homecare service perspective in Tuscany: vision and new user centred services.
AB  - "With medical knowledge expanding every day, no physician can keep up without
      help. By using high-tech medical communication, high-performance computers, high
      resolution video, and fibre-optic information "superhighways," we have been able
      to put the entire world of medical science at the fingertips of even the most
      isolated rural family doctor." [1] This quote by a former Surgeon General
      encapsulates the promise and potential for healthcare technology. Service
      organization and stakeholders' commitment are the real crucial issues for actual
      e-Health services deployment. In such a contest Homecare services start playing
      such a role of services integration and new care models development.

PMID- 16282664
TI  - A cataract decision support system: its requirement is increasing.
AB  - Cataract surgery and intraocular lens implantation has taken on many significant
      advances since its earliest inception. As the prevalence of the aged population
      increases the number of cataract operations also increases year on year. In the
      UK last year over 300,000 cataract operations were performed with 2 million in
      Europe and 1.5 million in the USA. Globally 8.7 million cataract operations are
      performed per annum. Technical advances are occurring ever more rapidly in this
      procedure enabling improved preoperative assessment and surgical management. This
      has produced a sophisticated procedure which is eminently reproducible. In
      concordance with such improvements both patient and doctors expectations for
      visual results have also risen. The expectation is now that the operation will
      achieve more than mere removal of a pathological opacity interfering with the
      visual process. The possibility and expectation is that the procedure will be
      tailored specifically to the patient in such a way that the best possible visual
      result will be achieved through customization of the surgical process to optimize
      the individual's optical system. Optimization of any particular process may be
      complex, and cataract surgery is no exception. Careful consideration of many
      interrelated factors including a patient's functional visual requirements, along
      with specific anatomical and unique optical factors will be required if an
      optimum result is to be achieved. The decision making process involved in
      determining how an individual eye should be surgically customised, can therefore
      be complicated. These are the situations where decision support systems become
      most beneficial, to ensure consistent successful results, particularly if
      technical measurements are being performed by individuals with varying degrees of
      experience.

PMID- 16282665
TI  - Context-aware infrastructure for personalized healthcare.
AB  - Ubiquitous computing is shifting healthcare from treatment by professionals in
      hospitals to self-care, mobile care, home care and preventive care. In order to
      support the healthcare evolution, a global healthcare system, which links
      healthcare service providers to an individual's personal and physical spaces, is
      expected to provide personalized healthcare services at the right time, right
      place and right manner. This paper presents an overall architecture for such a
      context-aware healthcare system. The key technologies such as device self-sensing
      mechanism, context processing framework and a service interoperability platform
      are identified and elaborated. A personalized healthcare adviser service has been
      described to illustrate how personalized healthcare can be well supported by the
      proposed infrastructure.

PMID- 16282666
TI  - Software and knowledge engineering aspects of smart homes applied to health.
AB  - Smart Home technology offers a viable solution to the increasing needs of the
      elderly, special needs and home based-healthcare populations. The research to
      date has largely focused on the development of communication technologies, sensor
      technologies and intelligent user interfaces. We claim that this technological
      evolution has not been matched with a step of a similar size on the software
      counterpart. We particularly focus on the software that emphasizes the
      intelligent aspects of a Smart Home and the difficulties that arise from the
      computational analysis of the information collected from a Smart Home. The
      process of translating information into accurate diagnosis when using non
      invasive technology is full of challenges, some of which have been considered in
      the literature to some extent but as yet without clear landmarks.

PMID- 16282667
TI  - End-to-end signal processing from the embedded body sensor to the medical end
      user through QoS-less public communication channels: the U-R-SAFE experience.
AB  - The URSafe project (IST-2001-33352) aims at creating a telemedicine care
      environment for the elderly and convalescent. The idea is to provide a portable
      device which monitors autonomously different biomedical signals and is able to
      send an alarm to a medical center if an abnormality is detected. In the initial
      version of URSafe, three sensors where included in the platform:
      electrocardiogram (ECG), oxygen rate (SpO2) and Fall Detector. This paper
      presents the signal processing algorithms involved in the project. These are at
      two levels: ECG analysis and signal transmission.

PMID- 16282668
TI  - IT-based diagnostic instrumentation systems for personalized healthcare services.
AB  - This paper describes recent research and development activities on the diagnostic
      instruments for personalized healthcare services in Seoul National University.
      Utilizing the state-of-the-art information technologies (IT), various diagnostic
      medical instruments have been integrated into a personal wearable device and a
      home telehealthcare system. We developed a wrist-worn integrated health
      monitoring device (WIHMD) which performs the measurements of non-invasive blood
      pressure (NIBP), pulse oximetry (SpO2), electrocardiogram (ECG), respiration
      rate, heart rate, and body surface temperature and the detection of falls to
      determine the onset of emergency situation. The WIHMD also analyzes the acquired
      bio-signals and transmits the resultant data to a healthcare service center
      through a commercial cellular phone. Two different kinds of IT-based blood
      glucometer have been developed using a cellular phone and PDA(personal digital
      assistant) as a main unit. A blood glucometer was also integrated within a wrist
      pressure measurement module which is interfaced with a cellular phone via
      Telecommunications Technology Association (TTA) standard in order to provide
      users with easiness in measuring and handling two important health parameters.
      Non-intrusive bio-signal measurement systems were developed for the ease of home
      use. One can measure his ECG on a bed while he is sleeping; measure his ECG, body
      temperature, bodyfat ratio and weight on a toilet seat; measure his ECG on a
      chair; and estimate the degree of activity by motion analysis using a camera.
      Another integrated diagnostic system for home telehealthcare services has been
      developed to include a 12 channels ECG, a pressure meter for NIBP, a blood
      glucometer, a bodyfat meter and a spirometer. It is an expert system to analyze
      the measured health data and based on the diagnostic result, the system provides
      an appropriate medical consultation. The measured data can be either stored on
      the system or transmitted to the central server through the internet. We have
      installed the developed systems on a model house for the performance evaluation
      and confirmed the possibility of the system as an effective tool for the
      personalized healthcare services.

PMID- 16282669
TI  - Networking and data management for health care monitoring of mobile patients.
AB  - The problem of medical devices and data integration in health care is discussed
      and a proposal for remote monitoring of patients based on recent developments in
      networking and data management is presented. In particular the paper discusses
      the benefits of the integration of personal medical devices into a Medical
      Information System and how wireless sensor networks and open protocols could be
      employed as building blocks of a patient monitoring system.

PMID- 16282670
TI  - Lifestyle support through efficient ECG acquisition and analysis.
AB  - People are becoming more aware of their health and the lifestyles they live. As
      people use computers more and more in a wide variety of occupations, they would
      find it desirable to monitor their lifestyle without having to leave their desk.
      Through the analysis of the Electrocardiogram (ECG), it is possible to obtain a
      person's heartrate and diagnose a number of conditions associated with abnormal
      heart function. To obtain an accurate heartrate, the ECG signals have to be
      analysed and calculations performed to find occurrences of the QRS complex, a
      major component of the ECG signal. This research entailed creating the software
      required to interpret ECG signals recorded from an innovative computer peripheral
      allowing recordings from the user's forearms as they operate the computer. The
      user could therefore effortlessly monitor their lifestyle during normal computer
      usage.

PMID- 16282671
TI  - Non-mediated glucose biosensing using nanostructured TiO2.
AB  - Insufficient insulin production in diabetics can be controlled by discontinuous
      measurement and insulin therapy. Ideally, an artificial pancreas system would be
      a closed loop system measuring glucose levels, and administering insulin as
      required, to minimise patient contribution. This paper presents an investigation
      into the use of titanium dioxide as an electrochemical transducer for the
      detection of hydrogen peroxide. Hydrogen peroxide is the product of glucose
      oxidation by the enzyme glucose oxidase in the presence of oxygen. The results
      show that peroxide can be quantitatively detected by electrochemical reduction on
      titanium dioxide electrodes without interference due to dissolved oxygen. When
      tested for the indirect amperometric measurement of glucose (with free glucose
      oxidase) it was found that the electrodes responded linearly over the range of
      glucose concentration found in human blood. With further development, these
      electrodes may be suitable for implantable glucose sensors.

PMID- 16282672
TI  - Detection and removal of pathogenic biofilms on medical implant surfaces.
AB  - Advances in sensor technology have had a significant impact in medical research
      and practice in the last decade. However, within the hospital environment
      problems still exist where the application of sensing technology could provide
      the solution. The presence of antibiotic resistant bacteria within hospitals and
      the risk of serious infection that they pose is a cause for concern. This paper
      describes a research project that has recently started at the University of
      Ulster investigating the potential of "Sense and Destroy" tactics to reduce the
      spread of medical device related infections. It is proposed that Electrical
      Impedance Spectroscopy (EIS) probes implanted within a catheter may be used to
      detect subclinical biofilm formation. Furthermore, if the presence of a biofilm
      is detected, activation of a photocatalytic coating on the catheter wall may be
      used to inactivate the responsible microorganisms.

PMID- 16282673
TI  - Development of a virtual reality system for the rehabilitation of the upper limb
      after stroke.
AB  - Virtual reality (VR) provides a three-dimensional computer representation of a
      real world or imaginary space through which a person can navigate and interact
      with objects to carry out specific tasks. One novel application of VR technology
      is in rehabilitation following stroke, particularly of the upper limb. This paper
      describes the development of a VR system for use in this field. This system gives
      the user the ability to interact with objects by touching, grasping and moving
      their upper limb.

PMID- 16282674
TI  - Monitoring of symptoms and interventions associated with multiple sclerosis.
AB  - We have utilized the Structured Data Entry approach to build a prototype
      interface for the recording of personalized symptoms associated with Multiple
      Sclerosis (MS). The software provides both graphical input and output, to
      facilitate efficient data entry and monitoring. Graphical input is transformed to
      textual information, which is stored in a database in a hierarchical tree
      structure. Pain management in MS may be achieved by careful monitoring of the
      symptom in response to treatment. Pain location is selected on a body image and
      severity and other attributes represented using a graphical visual analog scale,
      leading to more convenient input and a less ambiguous coding than is achievable
      with narrative text alone. The Internet can be used to record and provide access
      to clinical data, assisting the citizen by providing a healthcare professional
      partnership approach to care. This approach could provide an objective means of
      monitoring symptoms and hence provide a more personalized approach to MS
      management.

PMID- 16282675
TI  - Intelligent analysis of EMG data for improving lifestyle.
AB  - In the tragic situation when a person loses his or her hand, they are usually
      faced with only one option if they wish to regain a good level of mobility; learn
      to control an artificial hand. It has been suggested that our brain stores a
      "body map" of the different parts in our body. Thus, if a person loses a hand,
      their "body map" remains intact and produces phantom sensations that permit the
      person to feel like they still have their hand. Some discomfort is felt during
      these sensations; nevertheless, there is a positive side to them as they enable
      patients to control prosthetic replacements. Sensations experienced can be
      measured using a method known as Electromyography (EMG) and can be acquired and
      processed to control an artificial hand. This research involved the acquisition,
      analysis and classification of EMG signals through construction of a recording
      device and the development of classification models based on heuristic approaches
      and Artificial Intelligence classifiers based on Neural Networks to control
      artificial hands.

PMID- 16282676
TI  - Inhibition of parathyroid hormone: a dose equivalency study of paricalcitol and
      doxercalciferol.
AB  - INTRODUCTION: Paricalcitol and doxercalciferol are effective in reducing
      parathyroid hormone PTH concentrations in patients with secondary
      hyperparathyroidism. The purpose of this study was to determine the relative dose
      of doxercalciferol (compared to paricalcitol) required to maintain equivalent PTH
      concentrations in dialysis patients. METHODS: Chronic hemodialysis patients
      treated with a stable dose of paricalcitol for at least 3 months were randomized
      to receive doxercalciferol at either 35, 50, or 65% of the paricalcitol dose for
      6 weeks. Serum iPTH, calcium, phosphorus, and albumin were determined at baseline
      and monitored every 2 weeks. A linear regression analysis of percent change in
      iPTH values by dose group was performed to determine the conversion factor.
      RESULTS: 27 patients were enrolled. Initial iPTH, adjusted serum calcium, serum
      phosphorus, and CaxP were similar among the treatment groups. Linear regression
      analysis demonstrated a conversion factor of 0.57 for the dose of doxercalciferol
      relative to paricalcitol resulting in equivalent suppression of iPTH. Corrected
      serum calcium, phosphorus, CaxP product, as well as incidence of hypercalcemia,
      hyperphosphatemia and CaxP >50 were similar for all groups. CONCLUSION: In
      patients on a maintenance dose of paricalcitol, dosing doxercalciferol at 55-60%
      of the paricalcitol dose results in comparable inhibition of PTH.

PMID- 16282677
TI  - Activity of systemic lupus erythematosus in end-stage renal disease patients:
      study in a Brazilian cohort.
AB  - BACKGROUND: Dialysis has been associated with lupus remission. We studied the
      prevalence of systemic lupus erythematosus (SLE) as a cause of end-stage renal
      disease (ESRD) in the metropolitan area of Rio de Janeiro and assessed disease
      activity in SLE patients on dialysis. METHODS: Of 3,535 ESRD patients, 63 had SLE
      (1.8%). Fifty-seven entered the study (54 females, 3 males, 38 +/- 10 years).
      Hemodialysis consisted of 3 sessions per week of about 4 h duration, blood flow
      of about 400 ml/min, bicarbonate dialysate ([Ca(2+)] = 2.5-3.5 mEq/l) at 500
      ml/min and cellulose acetate or polysulfone dialyzers. Activity was initially
      defined as: non-renal (nr) SLE disease activity index (SLEDAI) of >0; use of at
      least 20 mg/day of prednisone; and/or any dose of another activity-controlling
      drug. Fifty-seven ESRD patients without SLE were used as controls. RESULTS:
      Eighteen SLE patients were under drug treatment; of the remaining, 30 had an
      nrSLEDAI of >0 totaling 48 patients (84%) initially labeled as active. An
      apparent activity was also present in 21 controls (37%). Of those, 19 had an
      nrSLEDAI of <4. With a cutoff of >or=4, figures in each group would be 49 and 4%.
      Under this criterion, age was the only significant predictor of flare in our SLE
      ESRD population in a multivariate logistic regression model. Activity remained
      high in patients who were on dialysis for >5 years (7/18, 39%). CONCLUSION: SLE
      accounted for 1.8% of our ESRD patients. Application of SLEDAI to dialysis
      patients may require consideration of confounding factors related to the ESRD
      state. Even with a score of >or=4 as a cutoff, SLE activity in dialysis patients
      was high (49%) and long-lasting. Age was the major determinant of flare.

PMID- 16282678
TI  - Glomerular and tubular epithelial defects in kd/kd mice lead to progressive renal
      failure.
AB  - BACKGROUND/AIM: The kd/kd mouse spontaneously develops severe and progressive
      nephritis leading to renal failure, characterized by cellular infiltration,
      tubular destruction and glomerular sclerosis. Recent identification of the mutant
      gene and the observation that podocytes are affected, led to the hypothesis that
      there are primary renal epithelial cell defects in this strain. METHODS: Clinical
      and pathological signs of disease in a large cohort of kd/kd mice were studied by
      light microscopy, electron microscopy, and biochemical analyses of serum and
      urine at early stages of disease. Special attention was paid to mice under 140
      days of age that had normal blood urea nitrogen (BUN) levels, but had developed
      albuminuria. RESULTS: Although overt glomerular abnormalities are commonly
      observed either coincident with or after tubulointerstitial nephritis, we now
      report that albuminuria and visceral epithelial abnormalities, including
      hyperplasia and podocyte effacement may occur before the onset of either elevated
      BUN levels or severe interstitial nephritis, and this is accompanied by
      biochemical perturbations in serum typical of the nephrotic syndrome.
      CONCLUSIONS: The results suggest that the defect in kd/kd mice primarily affects
      both the tubular and glomerular visceral epithelium. The tubular epithelial
      defect triggers autoimmune interstitial nephritis, whereas a defect in podocytes
      leads to proteinuria and glomerulosclerosis. Thus, a single mitochondrial
      abnormality may result in differences in disease expression that vary with the
      type of epithelial cells. It is likely that the mitochrondrial perturbations in
      glomerular and tubular epithelia act in concert, through activation of different
      pathologic pathways, to accelerate disease progression leading to renal failure.

PMID- 16282679
TI  - Characteristics of (+)-catechin and (-)-epicatechin transport across pig
      intestinal brush border membranes.
AB  - BACKGROUND/AIMS: (+)-Catechin and (-)-epicatechin are considered as disease
      preventive flavan-3-ols of foods like fruits, beverages and chocolate. We
      investigated mechanisms and kinetics of (+)-catechin and (-)-epicatechin uptake
      employing a validated in vitro model with isolated pig brush border membrane
      vesicles. METHODS: Vesicles were isolated from pig small intestine employing the
      divalent cation method. Characterization (marker enzymes, electron microscopy)
      confirmed their purity and function. Transport studies with (+)-catechin and (-)
      epicatechin under predefined conditions [presence/absence of sodium, pH gradient,
      temperature (8-37 degrees C), various initial substrate concentrations (2-20
      mmol/l)] revealed a measurable transport (HPLC analyses) across the brush border
      membrane for both substrates. RESULTS: Catechin transport was stimulated by an
      outwardly directed H(+) gradient (pH(i) 5.5/pH(o) 7.5). The presence of an
      inwardly directed Na(+) gradient did not result in a transient overshoot in (+)
      catechin and (-)-epicatechin uptake. At 37 degrees C, subtraction of diffusion
      from the total transport rate showed saturation kinetics. CONCLUSION: Our in
      vitro study indicate that both (+)-catechin and (-)-epicatechin are transported
      across the basolateral membrane using a dual transport system consisting of free
      diffusion (dominant at low concentrations) and carrier-mediated facilitated
      diffusion.

PMID- 16282680
TI  - Does body mass index predict overweight in native Asian Indians? A study from a
      North Indian population.
AB  - AIMS: Body mass index (BMI) has been considered as a gold standard for defining
      overweight and obesity, and in western populations it has correlated with
      percentage body fat (%BF). However, data in native Asian Indians regarding BMI
      and %BF is conflicting and questions have been raised to redefine the BMI cut-off
      values in these subjects. SUBJECTS AND METHODS: 150 healthy volunteers (79 men
      and 71 women aged 18-78 and 23-75 years respectively) were recruited for the
      study. Clinical examination was performed to exclude any systemic disease.
      Anthropometric measurements were done and %BF was calculated from skinfold
      thickness. RESULTS: The BMI for men was 24.96 kg/m(2) (+/-3.85) and for women was
      25.75 kg/m(2) (+/-4.39).%BF calculated by skinfold thickness was 21.94% (+/-5.92)
      in men and 35.15% (+/-5.77) in women. Receiver operating characteristic curve
      analysis showed a higher sensitivity (92%) and higher negative predictive value
      (95%) for the conventional cut-off value of the BMI (25 kg/m(2)) in identifying
      subjects with overweight with %BF of more than 25% in men. However, in females a
      BMI of 23.9 kg/m(2) had a sensitivity of 84% and negative predictive value of 62%
      thereby decreasing the misclassification by 13% with %BF of more than 30% as
      compared to conventional BMI cut-off of >25 kg/m(2). A comparison of BF data
      amongst Caucasians, Blacks and migrant ethnic Asians revealed inconspicuous
      differences in men. CONCLUSION: Native North Indian men had comparative BMI and
      %BF as that of their western counterparts.

PMID- 16282681
TI  - Relevance of meat fat content and fruit and vegetable intake for the oxidative
      status of pigs.
AB  - BACKGROUND: The aim of the present study was to evaluate the effect of
      substituting lean meat with fat meat on oxidative stress in a diet with or
      without fruit and vegetables. METHODS: Thirty-two pigs were divided into groups
      and fed isocaloric daily rations: LM+FV (balanced diet with lean meat and fruit
      and vegetables); FM+FV (as LM+FV, but lean meat was substituted with fat meat);
      LM-FV (as LM+FV, but without fruit and vegetables), and FM-FV (as FM+FV, but
      without fruit and vegetables). Oxidative stress was evaluated by measuring the 24
      hour urine malondialdehyde excretion rate, the degree of leukocyte nuclear DNA
      damage, the concentration of tocopherols in blood plasma, erythrocyte glutathione
      peroxidase activity and the total antioxidant status of plasma. RESULTS: The
      substitution of lean meat with fat meat modestly increased the rate of leukocyte
      DNA damage only in the diet with fruit and vegetables but had no effect in the
      group deprived of fruit and vegetables. Regardless of the fruit and vegetable
      content of the diet, the substitution of lean meat with fat meat did not affect
      any other parameters measured. In comparison to both fruit- and vegetable
      containing diets, the deprivation of fruits and vegetables in the LM-FV and FM-FV
      groups significantly increased the rate of leukocyte DNA damage and reduced the
      plasma alpha-tocopherol level (significant only for FM+FV). CONCLUSION: The
      substitution of fat meat with lean meat in a diet with or without fruit and
      vegetables has only a marginal or no effect on oxidative stress. But fruit and
      vegetable exclusion markedly increased the level of oxidative stress.

PMID- 16282682
TI  - Clinical course of hearing and language development in GJB2 and non-GJB2 deafness
      following habilitation with hearing aids.
AB  - Mutations in the GJB2 gene (connexin 26) are the most common cause of
      nonsyndromic autosomal recessive sensorineural hearing loss. Genetic testing of
      GJB2 may offer opportunities to predict the features of hearing loss and
      prognostication of speech-language development in children with hearing loss. The
      present study assessed the clinical features of hearing and some aspects of
      language development in congenital deafness due either to GJB2 mutations or to
      other factors in Japanese patients who had been habilitated with hearing aids.
      Thirty-five unrelated subjects with nonsyndromic, congenital, bilateral
      sensorineural hearing loss were enrolled in the study. Among them, 16 had
      biallelic GJB2 mutations related to hearing loss and 17 lacked such mutations. As
      has been reported in populations of European ancestry, the present Japanese
      subjects with GJB2 mutations had a relatively high incidence of the flat pattern
      audiogram and nonprogressive pure tone thresholds compared with subjects without
      GJB2 mutations. Subjects with GJB2 mutations and those without GJB2 mutations
      both showed a similar tendency in speech perception, some aspects of language
      development, and communication methods. In both groups, development of reading
      ability tended to be normal, but vocabulary development tended to be delayed. The
      present results establish the basis for future studies to aid in the evaluation
      and follow-up of patients with congenital hearing loss associated with GJB2
      mutations who are habilitated with hearing aids.

PMID- 16282683
TI  - Assessment of coronary artery disease in hemodialysis patients with delayed
      systolic blood pressure response after exercise testing.
AB  - BACKGROUND: We evaluated usefulness of the postexercise systolic blood pressure
      (SBP) response for detecting coronary artery disease (CAD) in hemodialysis
      patients. METHODS: A treadmill exercise testing was done, and the SBP response
      was measured in 44 hemodialysis patients (30 men, 14 women; age 41 to 81 years).
      The postexercise SBP response was defined as the ratio of SBP after 3 minutes of
      recovery to SBP at peak exercise. RESULTS: The SBP ratio of the 25 subjects with
      coronary artery stenosis (1.01+/- 0.13) was significantly greater (p<0.01) than
      19 subjects without coronary artery stenosis (0.83+/- 0.10). An SBP ratio greater
      than 0.92 identified CAD with higher sensitivity, specificity, and accuracy than
      did the conventional ST-segment depression criterion (76 vs. 56%, 90 vs. 53%, and
      82 vs. 55%, respectively). CONCLUSION: Determination of the SBP ratio is a
      clinically useful, noninvasive method for accurately detecting CAD in
      hemodialysis patients.

PMID- 16282684
TI  - Regional citrate anticoagulation during hemodialysis: a simplified procedure
      using Duocart biofiltration.
AB  - BACKGROUND: Regional citrate anticoagulation during hemodialysis is promising,
      but its clinical implementation is routinely cumbersome because a continuous
      adjustment of calcium infusion at the dialyzer outlet is needed. Duocart
      biofiltration (DCB) is a new hemodialysis method using a calcium and magnesium
      free dialysate containing only sodium chloride and bicarbonate combined with the
      infusion into the venous line of a solution containing the ionic complement (K,
      Ca, Mg) and glucose. Since the dialysate is calcium- and magnesium-free and
      infusion rate of the solution containing calcium is automatically determined by
      the dialysis delivery system according to the on-line measured value of ionic
      dialysance, DCB seems a technique especially suitable for citrate anticoagulation
      procedure. METHODS: Thirty DCB sessions were performed in 10 patients with
      increased risk of bleeding. A commercially available mixture of trisodium
      citrate, citric acid and glucose was infused into the arterial line at a rate
      equal to 3% of dialyzer blood flow. The ionic complement (K: 48 mM, Ca: 42 mM,
      Mg: 14 mM, glucose: 110 mM) was infused at a rate equal to 1/24 ionic dialysance
      value automatically determined each 15 min by the dialysis monitor. DCB sessions
      were compared to 21 conventional bicarbonate hemodialysis (BHD) sessions with low
      molecular-weight heparin anticoagulation. RESULTS: Whole blood activated clotting
      time (WBACT) measured in the venous line (before infusion of ionic complement)
      was 200% of the WBACT value in the arterial line. Clotting and citrate-related
      adverse events were not observed. Postdialysis compression time of the
      arteriovenous access is significantly (p<0.001) shorter after DCB sessions (3.9+/
      1.1 min) compared with BHD sessions (8.7+/-4.6 min). CONCLUSION: Citrate
      anticoagulation during Duocart biofiltration is effective, safe and suitable for
      routine use because calcium infusion rate is automatically adjusted without the
      need of monitoring degree of anticoagulation and level of ionized calcium.

PMID- 16282685
TI  - Pathophysiology of stroke rehabilitation: temporal aspects of neuro-functional
      recovery.
AB  - Stroke almost always causes an impairment of motor activity and function.
      Clinical recovery, though usually incomplete, is often highly dynamic and
      reflects the ability of the neuronal network to adapt. Mechanisms that underlie
      neuro-functional plasticity are now beginning to be understood. Albeit the
      enormous efforts undertaken to support the natural course of re-convalescence
      through rehabilitation, little has been done to relate possible effects of these
      therapeutic approaches to mechanisms of adaptive pathophysiology. The review
      presented here focuses on these mechanisms during the course of recovery post
      stroke. Next to an unmasking of latent network representations, other adaptive
      processes, such as excitatory metabolic stress, an imbalance in activating and
      inhibiting transmission, leading to salient hyperexcitability or mechanisms that
      consolidate novel connections prime the system's plastic capabilities. These
      pathophysiological processes potentially interact with rehabilitative
      interventions. They therefore form the foundation of positive, but possibly also
      negative recuperation under therapy.

PMID- 16282686
TI  - Moderate atheroma of the aortic arch and the risk of stroke.
AB  - BACKGROUND AND PURPOSE: Severe atheroma >or=4 or 5 mm of the aortic arch is a
      risk factor for stroke. We investigated the most predictive characteristics of
      arch atheroma, including maximal plaque thickness, for subsequent cardiovascular
      events, and also examined whether moderate atheroma<4 mm is a risk of cerebral
      emboli. METHODS: The maximal plaque thickness (MPT) and plaque morphologies of
      the aortic arch were evaluated by transesophageal echocardiography in 236
      patients with ischemic stroke. We assessed the relationship between the incidence
      of cardiovascular events, recurrent stroke or myocardial infarction, and the
      characteristics of the atheroma. We also investigated the thickness of atheroma
      in patients with known causes of stroke (n=148) and in patients with undetermined
      causes (n=19). RESULTS: Cardiovascular events occurred in 47 patients in the
      follow-up period with a mean of 3.5 years. MPT was a significant risk factor of
      the cardiovascular events, although plaque morphologies were not. For the
      receiver operator characteristics curve analysis, the suitable cutoff point of
      MPT associated with the cardiovascular events was 3.5 mm. Patients with MPT
      >or=3.5 mm had a higher risk of cardiovascular events than did those with MPT<3.5
      mm. In addition, aortic atheroma with MPT >or=3.5 mm was more frequently observed
      in patients with undetermined causes of stroke than those with known causes at 68
      vs. 39% (p=0.024). CONCLUSIONS: MPT >or=3.5 mm is the best predictor of
      subsequent cardiovascular events and a possible cause of embolic stroke.

PMID- 16282687
TI  - Nucleosomes in serum of patients with early cerebral stroke.
AB  - BACKGROUND: Nucleosomes are cell death products that are elevated in serum of
      patients with diseases that are associated with massive cell destruction. We
      investigated the kinetics of circulating nucleosomes after cerebral stroke and
      their correlation with the clinical status. METHODS: In total, we analyzed
      nucleosomes by ELISA in sera of 63 patients with early stroke daily during the
      first week after onset. For correlation with the clinical pathology, patients
      were grouped into those with medium to slight functional impairment (Barthel
      Index BI >or=50) and those with severe functional impairment (BI<50). RESULTS:
      Patients with BI >or=50 showed a continuous increase in nucleosomes until day 5
      (median: 523 arbitrary units, AU) followed by a slow decline. In contrast,
      patients with BI<50 showed a steeper initial increase reaching a maximum already
      on day 3 (869 AU). Both, days after stroke (p < 0.001) and BI (p < 0.001), had a
      significant influence on nucleosome concentrations, respectively. Consistently,
      patients with BI<50 had a significantly larger area under the curve (AUC/day) of
      nucleosome values during the first week after stroke (800 AU) than patients with
      BI >or=50 (497 AU; p=0.031). Concerning the infarction volume, nucleosomes showed
      significant correlations for the concentrations on day 3 (r=0.43; p=0.001) and
      for the area under the curve (r=0.34; p=0.016). CONCLUSION: Even if nucleosomes
      are nonspecific cell death markers, their release into serum after cerebral
      stroke correlates with the gross functional status as well as with the infarction
      volume and can be considered as biochemical correlative to the severity of
      stroke.

PMID- 16282688
TI  - Transcranial Doppler in adult patients with sickle cell disease.
AB  - BACKGROUND: Transcranial Doppler (TCD) is the key test in determining the need
      for prophylactic blood transfusion to prevent stroke in children with sickle cell
      disease (SCD). The role of TCD in assessing stroke risk in adults with SCD as
      well as the pattern of TCD velocities in these patients are still undetermined.
      METHODS: The authors compared TCD velocities in SCD adults (n=56) with those of
      healthy controls (n=56). RESULTS: Velocities in SCD adults were lower than those
      found in children and higher than in controls and negatively correlated to
      hematocrit in both groups. CONCLUSION: The pattern of TCD velocities in adults
      with SCD is different from that described in children. Age-specific TCD criteria
      may assist the detection of stroke risk in these patients.

PMID- 16282689
TI  - Stroke-in-evolution: infarct-inherent mechanisms versus systemic causes.
AB  - BACKGROUND: It is uncertain whether deterioration after acute ischemic stroke is
      neurological and/or systemic (somatic) in origin. METHODS: 442 consecutive
      patients admitted with first-ever ischemic stroke (FIS) were assessed by the
      Unified Neurological Stroke Scale (UNSS) at admission, on hospitalization days 1,
      2 and 3 and before discharge. RESULTS: Among 71/442 (16.1%) patients deteriorated
      during hospitalization, the worsening from stroke onset was early (<or=72 h) in
      67 (94.4%) of them. The majority (57/71, 80.3%) had CT-confirmed cerebral causes
      and 14/71 (19.7%) had systemic causes. The causes of late deterioration were
      exclusively systemic. In the logistic regression analysis the initial mean UNSS
      score was the only significant independent predictor of stroke deterioration (p <
      0.0001). CONCLUSIONS: Early clinical deterioration in FIS patients results from
      infarct-inherent mechanisms while late stroke deterioration is due primarily to
      systemic factors. An initially severe neurological deficit might predict further
      decline.

PMID- 16282690
TI  - Insular involvement is associated with QT prolongation: ECG abnormalities in
      patients with acute stroke.
AB  - PURPOSE: Aim was to assess the frequencies of electrocardiographic (ECG)
      abnormalities, including QT prolongation, in acute stroke patients and their
      association with stroke severity, stroke subtype and location, and cardiovascular
      risk factors. METHODS: Prospectively, admission 12-lead ECG findings, stroke
      characteristics, cardiovascular risk factors, and potential QT-prolonging factors
      were collected in 122 consecutive patients with acute stroke. RESULTS: Eighty
      four patients (69%) had ECG abnormalities, most frequently ST changes in 34%, QT
      prolongation in 31%, and atrial fibrillation in 27% of them. Insular involvement
      and prior stroke independently predicted QT prolongation in small infarcts
      (insular involvement OR 0.12, 95% CI 0.02-0.74, p=0.022; prior stroke OR 0.20,
      95% CI 0.06-0.70, p = 0.012). CONCLUSION: Continuous ECG monitoring and
      assessment of the QT interval should be mandatory in patients with acute stroke.

PMID- 16282691
TI  - Potential value of post stroke extracranial arterial blood flow volume in the
      prediction of stroke functional outcome.
AB  - BACKGROUND AND PURPOSE: Cerebral vasoreactivity and collateral circulation are
      important protective mechanisms against cerebral ischemia. Previous studies
      suggest that the efficiency of these mechanisms can be reflected by extracranial
      arterial blood flow volume. Brain damage leading to neurological impairments can
      influence patients' functional recovery after stroke. This study attempted to
      explore the potential value of post stroke extracranial arterial blood flow
      volume in the prediction of stroke patients' functional outcome. METHODS: We
      prospectively studied 362 consecutive patients who were hospitalized for recent
      acute strokes. All patients underwent extracranial arterial blood flow volume
      measurement of the carotid and vertebral arteries by color velocity imaging
      quantification within 3 days after admission. Their functional recovery was
      assessed 6 months after stroke. The effect of post stroke extracranial arterial
      blood flow volume on patients' functional outcome was tested by multivariate
      ordinal regression after controlling for other independent variables.
      Significance was at p<0.05. RESULTS: Post stroke extracranial arterial blood flow
      volume together with age, pre-stroke modified Rankin scale, the National
      Institutes of Health Stroke Scale and diabetes mellitus had significant effects
      on the patients' 6-month functional outcome as measured by the modified Rankin
      scale after controlling for other independent variables (p<0.05). CONCLUSIONS:
      Post stroke extracranial arterial blood flow volume is an independent outcome
      predictor. The graded predictive power of this parameter is potentially more
      superior than other outcome predictors by allowing classification of stroke
      outcome according to the degree of severity. A large prospective study is thus
      warranted to investigate its clinical value in the management of stroke patients.

PMID- 16282692
TI  - Selected observations on amusia.
AB  - Amusia appears primarily as a defect in processing pitch. The deficit extends to
      musical memory and recognition, singing and timing of music. Clinical studies of
      acquired brain lesions show that dysphasia is not necessarily accompanied by
      amusia, and acquired amusia without aphasia has been reported. These
      dissociations suggest some degree of autonomy in the function of these
      mechanisms.

PMID- 16282693
TI  - Human hearing modelling real-time spectrography for visual feedback in singing
      training.
AB  - The traditional form of spectrography employed for speech analysis makes use of
      fixed bandwidth bandpass filters, which are usually set either to wide-band or
      narrow-band to optimise the time and frequency resolution of the resulting
      spectrogram respectively. The acoustic analysis carried out by the human ear can
      be modelled as a bank of bandpass filters whose bandwidth changes as a function
      of centre frequency, and therefore the time and frequency resolution varies with
      frequency. This paper describes a spectrographic analysis technique that is based
      on peripheral human hearing and considers its potential for application within a
      real-time visual display for singing training by comparing its output with
      traditional wide- and narrow-band spectrograms. The potential advantages and
      disadvantages of hearing modelling spectrography for this application are
      illustrated and discussed for a selection of sung material, some of which has
      been recorded during singing lessons where traditional spectrography is being
      employed.

PMID- 16282694
TI  - Estimates of African, European and Native American ancestry in Afro-Caribbean men
      on the island of Tobago.
AB  - BACKGROUND/AIMS: The Tobago Afro-Caribbean population is a valuable resource for
      studying the genetics of diseases that show significant differences in prevalence
      between populations of African descent and populations of other ancestries.
      Empirical confirmation of low European and Native American admixture may help in
      clarifying the ethnic variation in risk for such diseases. We hypothesize that
      the degree of European and Native American admixture in the Tobago population is
      low. METHODS: Admixture was estimated in a random sample of 220 men, from a
      population-based prostate cancer screening survey of 3,082 Tobago males, aged 40
      to 79 years. We used a set of six autosomal markers with large allele frequency
      differences between the major ethnic populations involved in the admixture
      process, Europeans, Native Americans and West Africans. RESULTS: The ancestral
      proportions of Tobago population are estimated as 94.0+/-1.2% African, 4.6+/-3.4%
      European and 1.4+/-3.6% Native American. CONCLUSIONS: We conclude that Tobago
      Afro-Caribbean men are predominantly of West African ancestry, with minimal
      European and Native American admixture. The Tobago population, thus, may carry a
      higher burden of high-risk alleles of African origin for certain diseases than
      the more admixed African-American population. Conversely, this population may
      benefit from a higher prevalence of protective alleles of African origin.

PMID- 16282695
TI  - Association of depression with markers of nutrition and inflammation in chronic
      kidney disease and end-stage renal disease.
AB  - BACKGROUND: Depression, which is the most common psychological disorder among
      patients with end-stage renal disease (ESRD), is commonly associated with poor
      oral intake which can aggravate anemia and malnutrition in chronic dialysis
      patients. The objective of this study is to explore the association between
      depression and C-reactive protein (CRP), ferritin, serum albumin and
      hemoglobin/hematocrit in patients with chronic kidney disease (CKD) and ESRD.
      METHODS: Sixty-eight patients on hemodialysis (HD), 47 patients on continuous
      ambulatory peritoneal dialysis (CAPD) and 26 patients with CKD on conservative
      management were enrolled in this study. All patients were evaluated for the
      presence of depression using the Structured Clinical Interview for Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I Disorders
      Clinician Version (SCID-CV). The severity of depression was evaluated by means of
      the Beck Depression Inventory (BDI). Serum CRP (nephelometric method), ferritin
      (immunometric method), albumin (bromcresol green technique), hemoglobin, and
      hematocrit levels were measured. RESULTS: A total of 34 of 141 patients (24.1%)
      had depression. The mean BDI score was higher in depressive patients compared to
      nondepressive patients. In HD patients the frequency of depression and CRP and
      ferritin levels were higher than in other groups. Patients with depression had
      lower hemoglobin, hematocrit and serum albumin levels and higher CRP and ferritin
      levels than patients without depression. The BDI score showed a positive
      correlation with serum CRP and ferritin levels, but a negative correlation with
      the serum albumin level. CONCLUSIONS: We observed that CKD and ESRD patients with
      anemia, hypoalbuminemia and higher serum CRP and ferritin concentrations should
      be evaluated for depression after potential somatic causes have been eliminated.

PMID- 16282696
TI  - High serum C3 predicts poor outcome in IgM nephropathy.
AB  - BACKGROUND: IgM nephropathy (IgMN) is an idiopathic glomerulonephritis with
      mesangial IgM deposition. The etiology of the depositions and possible
      association of serum and mesangial immunoglobulins and complement findings with
      renal outcome in IgMN remain unknown. Here we brought out data supplementary to
      our previous findings by reporting associations of immunological parameters with
      the outcome of IgMN. METHODS: Serum IgA, IgG, IgM, C3 and C4 were measured in 110
      IgMN patients by single radial immunodiffusion or nephelometry. Mesangial IgA,
      IgG, IgM, C1q and C3 assessed in immunofluorescent study were graded as +/-.
      Seven histopathological parameters were semiquantitatively graded into three
      classes. The relationship of serum and mesangial immunoglobulin and complement
      findings with the clinical outcome and prognosis of IgMN was examined. RESULTS:
      We found significantly lower serum IgG and higher serum C3 levels in patients
      with nephrotic syndrome. Serum C3 correlated with the severity of glomerular
      histopathological changes. Of immunological parameters evaluated a low serum
      IgG/C3 ratio correlated best with the progression of renal disease. However,
      serum C3 was associated independently with progression in the case of patients
      without nephrotic syndrome. CONCLUSIONS: In addition to previously reported
      factors, immunological parameters may also be helpful in determining the
      prognosis in IgMN. High serum C3 predicts poor outcome in IgMN, being associated
      with high-grade proteinuria, severe histopathological changes and progression.

PMID- 16282697
TI  - Clopidogrel diminishes hemodialysis access graft thrombosis.
AB  - BACKGROUND: The most common complication of hemodialysis (HD) access graft is
      thrombosis. Clopidogrel, an inhibitor of platelet aggregation, was assessed to
      prevent this serious complication. METHODS: A prospective study in which 24
      patients on chronic HD whose vascular accesses were grafts were divided into two
      groups: group A (n = 12, 50%) consisted of patients who did not receive
      antithrombotic therapy after graft creation, and group B (n = 12, 50%) received
      clopidogrel 75 mg/day from 2 days after surgery onwards. Both groups were not
      different according to age, gender, cause of renal failure, hematocrit levels,
      platelet counts and Kt/V. All patients' thrombotic episodes were followed up from
      the day of graft surgery until thrombosis was diagnosed. Finally, the patient
      survival difference between both groups was determined. RESULTS: Eleven
      thrombotic episodes were diagnosed in group A while one event was reported in
      group B (p < 0.001). Graft access days of patency were significantly longer in
      group B compared to group A (380.8 +/- 170 vs. 90.1 +/- 57.2, p < 0.001). Time
      that elapsed from dialysis initiation to graft creation was not different (group
      A 18 +/- 12 days, group B 20 +/- 10 days). Days on HD were different between both
      groups (group A 208.9 +/- 97.2 vs. group B 583.2 +/- 287.0, p < 0.001) and all
      patients from group A (n = 12, 100%) and 2 patients from group B (16.7%) died (p
      = 0.001). Major bleeding events were not reported. CONCLUSIONS: Clopidogrel
      significantly decreased thrombotic graft episodes. Patients on clopidogrel had a
      prolonged vascular access patency, longer time on HD and better survival.

PMID- 16282698
TI  - Upregulation of thymidine phosphorylase in chronic glomerulonephritis and its
      role in tubulointerstitial injury.
AB  - Chronic tubulointerstitial injury (CTI), commonly a sequel to chronic
      glomerulonephritis (CGN), is associated with the proliferation of new blood
      vessels. Angiogenesis is an essential process in chronic inflammation, and is
      controlled by a number of angiogenic factors including thymidine phosphorylase
      (TP). Knowledge of TP in renal disease is still rudimentary, and its role in CGN
      has not been explored. We analyzed the expression of TP by RTPCR, immunohistology
      and in situ hybridization in 20 human kidneys with CGN. To evaluate the degree of
      angiogenesis, we counted the microvessel density (MVD). MVD was significantly
      higher in all categories of CGN, between 19.7 +/- 7.7 and 58.9 +/- 7.5, compared
      to control value, 12.7 +/- 5.0 (p < 0.05). MVD was increased in areas of abundant
      mononuclear cell infiltration with minimal interstitial fibrosis, and decreased
      or absent in areas of marked fibrosis. There was a significant correlation
      between MVD and interstitial fibrosis (p < 0.0001). TP mRNA was upregulated for
      all categories of CGN. TP was strongly expressed by mononuclear inflammatory
      cells and in most atrophic tubules. Each MVD and interstitial volume was
      significantly correlated with both the number of TP+ mononuclear cells and TP+
      tubular cells, respectively (p < 0.0001). We have demonstrated an upregulation of
      TP and increase in MVD in areas of CTI in a variety of CGN. The up-regulation of
      TP may contribute to angiogenesis, which may play a critical role in the
      progression of interstitial fibrosis in CGN.

PMID- 16282699
TI  - Pamidronate therapy for preventing steroid-induced osteoporosis in children with
      nephropathy.
AB  - BACKGROUND: Steroid-induced osteoporosis (SIO) is a serious complication of long
      term steroid therapy and is of particular concern in growing children. Recently
      bisphosphonates have been applied in the treatment or prevention of SIO. We
      investigated the efficacy of pamidronate on SIO in childhood nephropathy patients
      receiving long-term corticosteroid therapy. METHODS: Forty-four children
      receiving high doses of steroids were enrolled in the study. There was no history
      of bone, liver, or endocrine disease. Patients were randomly classified into two
      groups, the control group and the study group. All patients received
      corticosteroids for 3 months. Control group took oral calcium supplements (500
      mg/day) only, and the study group oral calcium and pamidronate (125 mg) for 3
      months. Biochemical tests, long bone radiography, and bone mineral density (BMD)
      were performed in the first month and 3 months later in all patients. RESULTS:
      The differences in the results of biochemical tests such as serum calcium, BUN,
      and creatinine level obtained in the first month and three months later were not
      of statistical significance in both the control and the study groups. However,
      the mean BMD of the lumbar spine decreased from 0.654 +/- 0.069 (g/cm2) to 0.631
      +/- 0.070 (g/cm2) in the control group (p = 0.0017), while it did not in the
      study group from 0.644 +/- 0.189 (g/cm2) to 0.647 +/- 0.214 (g/cm2). CONCLUSIONS:
      Pamidronate appears to be effective in preventing SIO in children with
      nephropathy requiring long-term steroid therapy. Further long-term follow-up
      studies regarding the efficacy and side effects appear to be necessary to set a
      more solid basis for such pediatric uses of bisphosphonates such as pamidronate.

PMID- 16282700
TI  - Erythropoietin-alpha dosage requirements in a provincial hemodialysis population:
      effect of switching from subcutaneous to intravenous administration.
AB  - BACKGROUND: The purpose of this initiative was to compare erythropoietin-alpha
      doses in hemodialysis patients who changed from subcutaneous to intravenous
      administration. The Manitoba Renal Program switched routes due to concern about
      erythropoietin-associated pure red cell aplasia. METHODS: We compared the
      erythropoietin-alpha dosage requirements during subcutaneous administration (3
      months pre-switch) and intravenous administration (months 4-6 post-switch). We
      also compared: hemoglobin, transferrin saturation (Tsat%), ferritin, and percent
      of patients receiving intravenous iron. The same erythropoietin-alpha regimen was
      initially used when patients were switched. RESULTS: Of the 628 patients
      receiving erythropoietin-alpha, the data were complete for 400. The dose
      increased 26% (mean +/- SD, 10,425 +/- 7,330 vs. 13,125 +/- 8,638 IU/week; p <
      0.0001), despite similar hemoglobin, (mean +/- SD, 11.5 +/- 1.1g/dl (114.9 +/-
      11.2 g/l) vs. 11.3 +/- 1.0 g/dl (113.5 +/- 10.4 g/l); p = 0.0450) and iron
      parameters (Tsat 30.9%, ferritin 464 ng/ml (microg/l) vs. Tsat 28.7%, ferritin
      538 ng/ml (microg/l)). For the subgroup of 84 patients who maintained target
      hemoglobin (10-11 g/dl or 110-120 g/l) for both periods, the dose increased 26%
      (mean +/- SD, 8,393 +/- 6,242 vs. 10,589 +/- 7,049 IU/week; p < 0.0001) without a
      change in hemoglobin, (mean +/- SD, 11.5 +/- 0.3 g/dl (115.2 +/- 3.0 g/l) vs.
      11.5 +/- 0.3 g/dl (114.9 +/- 3.3 g/l); p = 0.5789). When stratified by
      subcutaneous dose, patients with the lowest dose (<5,000 IU/week) demonstrated
      the greatest increase (89%), and those with the highest dose (>20,000 IU/week)
      experienced no increase (-3%). CONCLUSION: Overall, erythropoietin-alpha doses
      increased by 26% when patients were converted from subcutaneous to intravenous
      administration.

PMID- 16282701
TI  - Serum mannose-binding lectin levels in maintenance hemodialysis patients: impact
      on all-cause mortality.
AB  - BACKGROUND/AIMS: Mannose-binding lectin (MBL) is characteristic of an acute-phase
      reacting protein like C-reactive protein (CRP). However, the prognostic value of
      the serum MBL level has not been examined. The aim of this study was to evaluate
      whether the serum MBL level can predict all-cause mortality in hemodialysis (HD)
      patients. METHODS: A total of 131 patients without active infection, who had been
      on maintenance HD for at least 2 years, were included in this study. The serum
      MBL, high-sensitivity CRP (hs-CRP) level, nutrition markers, and biochemical
      parameters were measured in June 1999. The cohort was then followed prospectively
      for 36 months, and clinical data were recorded. RESULTS: The MBL level of the 131
      HD patients was 9.054 +/- 5.115 microg/ml (mean +/- SD). During the follow-up
      period, 18 patients (9 males and 9 females) died and 113 (64 males and 49
      females) survived. The two leading causes of death were cardiovascular events (n
      = 6, 33.3%) and infection (n = 4, 22.2%). The serum MBL level was significantly
      lower among the nonsurvivors (6.596 +/- 4.990 microg/ml) than among the survivors
      (9.445 +/- 5.046 microg/ml; p < 0.05). There was a significant, although very
      weak, correlation between the MBL level and albumin level (p < 0.05), but there
      was no correlationbetween the MBL level and the hs-CRP level. The patients were
      divided into two groups according to the serum MBL level (< 5 and > 5 microg/ml).
      Multivariate analysis of factors predicting all-cause mortality in multivariate
      logistic regression analysis identified a serum MBL level < 5 microg/ml as a
      variable that independently predicted all-cause mortality (adjusted odds ratio:
      7.632; 95% CI: 2.244-25.961; p = 0.0011). Other significant and independent
      predictors for mortality included the hs-CRP level (every 100 microg/dl
      increase), hypertension and diabetes mellitus. CONCLUSIONS: Our findings suggest
      that the serum MBL level is a significant predictor of outcome in HD patients. HD
      patients with a low level of serum MBL should be carefully monitored.

PMID- 16282702
TI  - Genetic studies of IgA nephropathy.
AB  - IgA nephropathy is the commonest form of glomerulonephritis worldwide, but we
      still know relatively little about its pathogenesis. Potentially, genetic studies
      might provide new insights and suggest novel therapeutic approaches to this
      important cause of chronic kidney disease. Two approaches that are likely to
      yield new information are analysis of multiply affected pedigrees and large
      scale, well-controlled association studies.

PMID- 16282703
TI  - Expression of B7-H1 in inflammatory renal tubular epithelial cells.
AB  - BACKGROUND: Renal tubular epithelial cells (TECs) function as antigen-presenting
      cells (APCs) as they constitutively express MHC-II molecules and have the
      capacity to present peptide antigen to T cells. Nevertheless, co-stimulatory
      signals provided by TECs for regulating T cell activation have not been fully
      characterized. We therefore investigated the expression of B7-H1, a member of the
      B7 superfamily, on TECs under normal or pathologic conditions in vivo and
      analyzed the regulation and functional role of it after proinflammatory factors
      treatment in vitro. METHODS: Immunohistological staining for B7-H1 on cryostat
      sections of core needle biopsies from patients with different renal diseases was
      examined. Furthermore, we also detected B7-H1 protein expression on cultured
      human TECs stimulated by various inflammatory factors and performed TEC/T-cell co
      cultured experiment to determine TEC-associated B7-H1 in regulating CD4+ T cell
      activation as well as antigen presentation. RESULTS: Significant B7-H1 protein
      was detected in TECs of diseased renal samples. Although the presence of B7-H1
      does not have any correlation with clinicopathological variables, marked B7-H1
      expression on sections without interstitial inflammation revealed that B7-H1 has
      some protective function. In vitro, the expression of B7-H1 on TECs was increased
      after TECs were stimulated with IL-1alpha, LPS, TNF-alpha, IFN-gamma or anti
      CD40. Co-cultured experiments revealed that TEC-related B7-H1 was identified as a
      strong inhibitor of CD4+ T-cell activation as assessed by increased cytokine
      production (interleukin-2 and interferon-gamma) and expression levels of the T
      cell activation marker (CD69) in the presence of a neutralizing antibody against
      B7-H1 (clone MIH1). Interestingly, IL-2 production by C10 T cells after antigen
      presentation by murine TECs was also enhanced when the B7-H1/PD-1 pathway was
      interrupted. CONCLUSION: This study clearly shows that B7-H1 is an inducible
      renal tubular epithelial antigen that inhibits T cell activation. It is
      speculated that B7-H1/PD-1 pathway might play a role in protecting tubular
      epithelium from immune-mediated damage and active delivery of the B7-H1
      inhibitory signal represents a novel therapeutic strategy in autoimmune renal
      diseases.

PMID- 16282704
TI  - Murine metanephric mesenchyme possesses characteristics of vascular endothelial
      cells in vitro.
AB  - BACKGROUND/AIMS: Although the renal microvasculature, including the glomerular
      capillaries, is generally considered to develop from the metanephric mesenchyme,
      this has not been unequivocally demonstrated. Using a murine metanephric
      mesenchymal cell line (MS7), we tested whether the metanephric mesenchyme
      expresses phenotypic characteristics of endothelial cells and differentiates into
      vascular endothelial cells in vitro. METHODS: MS7 cells were examined for the
      mRNA expression of endothelial markers by reverse transcription (RT)-PCR.
      Moreover, we attempted to induce the appearance of new endothelial markers by
      stimulation with growth factors and exposure to hypoxia. RESULTS: Before
      induction, MS7 cells expressed mRNA of fetal liver kinase 1 (Flk1), fms-like
      tyrosine kinase (Flt1), tyrosine kinase with Ig and EGF homology domains 2
      (Tie2), CD31, and podocalyxin. However, they did not express mRNA for vascular
      endothelial-cadherin (VE-cadherin) or von Willebrand factor (vWF), which are
      markers specific for endothelial cells and mature endothelial cells. In the
      immunocytochemical analysis, MS7 absorbed DiI-acetylated LDL virtually, but the
      results of staining with anti-VE-cadherin, vWF, or CD31 antibodies were negative.
      MS7 cells that were cultured for 14 days after reaching confluence began to
      express VE-cadherin and vWF mRNA. In addition, immunofluorescence showed abundant
      granules stained with anti-vWF antibody in the cytoplasm. Stimulation with
      vascular endothelial growth factor (VEGF), or basic fibroblast growth factor
      (bFGF), or exposure to a hypoxic condition did not influence their characteristic
      changes. CONCLUSION: Our results suggest that metanephric mesenchymal (MS7) cells
      possess some characteristics of endothelial cells, and they are potent to
      differentiate into mature vascular endothelium in vitro.

PMID- 16282705
TI  - Induction and coexpression of latent transforming growth factor beta-binding
      protein-1 and fibrillin-1 in experimental glomerulonephritis.
AB  - BACKGROUND: Latent transforming growth factor-beta-binding protein 1 (LTBP-1) and
      fibrillin-1 were shown to colocalize and interact in the extracellular matrix of
      the skin and vasculature. This interaction may regulate transforming growth
      factor-beta (TGF-beta) activity. TGF-beta is an important progression factor for
      glomerular diseases. We hypothesized that LTBP-1 and fibrillin-1 are coexpressed
      in the glomerulus and upregulated during glomerulonephritis. METHODS: Acute anti
      Thy1.1 glomerulonephritis was induced with a single intravenous injection (1
      mg/kg body weight) of a monoclonal anti-Thy1.1 antibody in rats. Real-time RT-PCR
      and immunohistochemical analyses for LTBP-1 and fibrillin-1 were performed.
      RESULTS: Induction of glomerular LTBP-1 mRNA was detected on day 2 of disease,
      while mRNA for fibrillin-1 was already upregulated 1 day after induction of
      disease. Both LTBP-1 and fibrillin-1 showed a mesangial distribution. An
      expansion of the LTBP-1 and fibrillin-1-positive mesangial area was seen on day 6
      of disease, when transient matrix accumulation was most prominent. On day 12 of
      disease, glomerular LTBP-1 and fibrillin-1 immunoreactivities had returned to
      control levels. In serial sections, some colocalization of LTBP-1 and fibrillin-1
      was detected in control as well as in nephritic glomeruli. CONCLUSION: Mesangial
      expression of LTBP-1 and fibrillin-1 is induced early in experimental nephritis
      and LTBP-1 and fibrillin-1 are partially colocalized in the nephritic glomerulus.
      An interaction of these molecules could stabilize latent TGF-beta complexes and
      thus attenuate the activation of TGF-beta during this self-limited glomerular
      disease.

PMID- 16282706
TI  - Present status and perspectives in the treatment of hormone-refractory prostate
      cancer.
AB  - The cornerstone in the treatment of de novo or recurrent metastatic prostate
      cancer is androgen deprivation. Unfortunately, nearly all patients will develop
      androgen-independent ('hormone-refractory') disease with progressive clinical
      deterioration and ultimately death. Chemotherapy has been shown to palliate
      symptoms of hormone-refractory disease but not to improve survival. Recently, two
      large phase III trials have demonstrated an overall survival advantage for
      patients treated with docetaxel-based regimens as compared to the best standard
      of care. Indeed, investigations into the pathophysiology of this malignancy,
      novel biological agents, skeletal protectants and radiopharmaceuticals are
      expanding the clinician's armamentarium and improving the patient's outcome.

PMID- 16282707
TI  - An alternating regimen of irinotecan/ 5-fluorouracil/folinic acid and
      oxaliplatin/ 5-fluorouracil/folinic acid in metastatic colorectal cancer: a Phase
      II trial.
AB  - OBJECTIVE: To assess the feasibility and activity of a combination schedule with
      irinotecan (CPT-11), oxaliplatin (L-OHP), brief infusional fluorouracil (5-FU)
      and folinic acid (FA) as first-line treatment in metastatic colorectal cancer
      (MCC) patients. METHODS: Fifty consecutive patients were treated with CPT-11 125
      mg/m2 as a 90-min intravenous infusion, followed by FA 20 mg/m2 as an intravenous
      bolus, and 5-FU 500 mg/m2 over a 2-hour intravenous infusion on days 1 and 8. L
      OHP was administered at 85 mg/m2 over 2 h on day 15, in combination with a FA 60
      mg/m2 intravenous bolus and 5-FU 600 mg/m2 as a 2-hour intravenous infusion on
      days 15-16. The treatment was repeated every 4 weeks for a maximum of 9 cycles.
      RESULTS: Twenty-five of 50 assessable patients achieved a complete (n=5) or
      partial (n=20) response, leading to a response rate of 50% (95% CI 35-64%).
      Eighteen (36%) patients showed stable disease. The median time to tumor
      progression was 10.3 months (95% CI 9.6-10.9 months). After a median follow-up of
      16.4 months, the median survival was not reached. Grade 3 neutropenia (8%), grade
      3 nausea/vomiting (6%) and grade 3 diarrhea (2%) were the major adverse events.
      CONCLUSION: This alternating three-drug regimen is very well tolerated,
      manageable and effective in terms of activity and time to progression.

PMID- 16282708
TI  - Combination chemotherapy in advanced small bowel adenocarcinoma.
AB  - OBJECTIVE: To assess the efficacy of 5-fluorouracil (5-FU) and either platinum
      compounds or irinotecan in patients with advanced small bowel adenocarcinoma
      (SBA), for whom data on the efficacy of chemotherapy are scarce. METHODS: We
      reviewed data on all patients with advanced SBA who received chemotherapy over a
      9-year period at our institution. RESULTS: Twenty patients with advanced SBA
      received a median of 6 cycles (range 2-15) of chemotherapy with 5-FU and either
      cisplatin (n=15), carboplatin (n=2), or oxaliplatin (n=3). The overall response
      rate was 21%, and median progression-free and overall survival 8 and 14 months,
      respectively. Toxicity was moderate. Second-line chemotherapy with 5-FU and
      irinotecan resulted in disease stabilization in 4 (50%) of 8 patients (median
      progression-free survival: 5 months), and in a biological complete response in
      another patient with non-measurable peritoneal carcinomatosis, allowing surgical
      cytoreduction surgery and hyperthermic intraperitoneal chemotherapy. No tumor
      response or disease stabilization was seen among the patients who received
      protracted venous infusion of 5-FU (n=4) or infusional 5-FU and cisplatin (n=1)
      as second-line chemotherapy. CONCLUSION: Chemotherapy with 5-FU and platinum
      compounds seems effective and well-tolerated in patients with advanced SBA. 5-FU
      irinotecan combination chemotherapy deserves further investigation in the first
      line setting.

PMID- 16282709
TI  - Paclitaxel, carboplatin and gemcitabine combination as induction chemotherapy for
      stage IIIA N2 bulky non-small cell lung cancer.
AB  - BACKGROUND: Induction chemotherapy followed by surgical resection or definitive
      radiotherapy for patients affected by stage IIIA N2 bulky non-small cell lung
      cancer (NSCLC) has been investigated in several trials. PATIENTS AND METHODS: In
      this present study, 52 patients with stage IIIA N2 bulky NSCLC with cytologically
      or histologically confirmed mediastinal lymph node involvement received
      paclitaxel 175 mg/mq on day 1, carboplatin AUC 5 on day 1 and gemcitabine 1,000
      mg/mq on day 1 and 8 every 3 weeks for three cycles as induction chemotherapy.
      RESULTS: Objective response (4 complete remission and 36 partial remission) was
      achieved in 40/52 patients. No early or toxic deaths were observed. Twenty-two
      patients were surgically explored. Fifteen were excluded for resection for biopsy
      proven residual tumour in mediastinal nodes. Complete surgical resection was
      performed in 15 patients with confirmed pathological downstaging. Pathological
      complete response was achieved in 4 patients. No surgery-related mortality or
      significant morbidity was reported. Adjuvant radiotherapy was delivered in 15
      patients, and 30 patients received definitive radiotherapy. CONCLUSION: In the
      present study, the combination of paclitaxel, carboplatin and gemcitabine has
      been a safe and active regimen in poor-prognosis stage IIIA N2 bulky NSCLC.

PMID- 16282710
TI  - Expression of N-acetylglucosaminyltransferase V in the development of human
      esophageal cancers: immunohistochemical data from carcinomas and nearby
      noncancerous lesions.
AB  - OBJECTIVE: N-Acetylglucosaminyltransferase V (GnT-V) is a key enzyme in the
      formation of branching asparagine-linked oligosaccharides and is linked to tumor
      invasion and metastasis in colon and breast cancers. In normal esophageal
      epithelium, beta1,6-branched asparagine-linked oligosaccharides synthesized by
      GnT-V are seen in the basal cell layers but not in the superficial cell layers,
      and its presence has been shown in invasive esophageal cancers. However, neither
      GnT-V expression nor its clinical significance has been previously examined in
      human normal, premalignant and malignant esophageal tissues. METHODS: GnT-V
      expression was studied by immunohistochemistry using a specific monoclonal
      antibody in 121 surgically resected specimens of esophageal squamous cell
      carcinomas (SCCs) and adjacent tissues, and was analyzed statistically in
      relation to various characteristics. RESULTS: GnT-V expression was observed in
      none (0%) of the 19 normal epithelial tissues, 1 (2%) of the 43 hyperplastic
      tissues, 30 (54%) of the 56 mildly dysplastic tissues, 27 (63%) of the 43
      moderately dysplastic tissues, 21 (44%) of the 48 in situ SCCs and 29 (26%) of
      the 110 invasive SCCs (p<0.005). GnT-V expression was observed significantly more
      frequently in mildly and moderately dysplastic tissues when compared with normal
      epithelial and hyperplastic tissues (p<0.005), and its frequency was decreased in
      in situ and invasive SCCs (p<0.005). GnT-V expression was frequently observed in
      SCCs of small size and without distant metastasis or lymph node metastasis.
      CONCLUSIONS: Increased expression of GnT-V is associated with the early event of
      esophageal tumorigenesis.

PMID- 16282711
TI  - A phase II study of the docetaxel-ifosfamide-carboplatin combination in advanced
      non-small-cell lung cancer.
AB  - PURPOSE: In the present phase II study we evaluated the docetaxel-ifosfamide
      carboplatin (DICb) combination in the outpatient setting in patients with
      advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with
      advanced NSCLC (stages IIIB/IV), WHO performance status (PS) <2, and no prior
      chemotherapy were eligible. Chemotherapy drug doses were: docetaxel: 80 mg/m2,
      ifosfamide: 3.5 g/m2, and carboplatin at a target area under the curve of 5
      (based on Calvert's formula), all on day 1, followed by prophylactic G-CSF.
      RESULTS: Fourty patients were entered and all are evaluable for response and
      toxicity: median age: 64 (48-72); PS: 1 (0-1); gender: 29 males/11 females;
      stages: IIIB: 13 (33%), IV: 27 (67%). Metastatic sites at diagnosis included:
      lymph nodes: 25; bone: 7; liver: 4; brain: 5; lung nodules: 13; adrenals: 6.
      Responses were as follows: 22/40 [55%; 95% confidence interval (CI), 54-81%]
      evaluable patients responded: 4 complete responses, 18 partial responses, 11 had
      stable disease, and 7 had progressive disease. The median response duration was 7
      months (range 2-14 months), median time to progression 9 months (range 2-18
      months) and median overall survival 11 months (range 3-46+ months). 1-year
      survival was 47.5%. Grade 3/4 toxicities included: neutropenia 28/40, with 12
      developing grade 4 and 12% febrile neutropenia, thrombocytopenia grade 3: 3/40
      and grade 4: 1/40, no grade 3 neuropathy, grade 1 CNS toxicity in 3, no renal
      toxicity, 8 grade 2 diarrhea and 4 grade 3 vomiting. CONCLUSION: In the present
      phase II study the DICb combination yielded important activity and good
      tolerability in advanced NSCLC.

PMID- 16282712
TI  - Effect of thrombin on permeability of human epithelial cell monolayers.
AB  - Epithelial cells play an important role in maintaining the airway barrier, which
      is impaired in inflammatory conditions. Recently, thrombin was reported to be
      increased in the airway of patients with asthma, and thrombin has been shown to
      increase the permeability of endothelial cell monolayers. Therefore, we suspected
      that thrombin affects airway permeability. Calu-3 cell monolayers were
      established on microporous membranes of tissue culture cell inserts. We examined
      the effects of topically applied thrombin or thrombin receptor-activating peptide
      (TRAP) on: (1) transepithelial permeability (luminal to serosal transfer) of
      radiolabeled mannitol and albumin, (2) changes in electrical resistance, and (3)
      actin fiber content as assessed by fluorescence microscopy. Compared with
      untreated control cultures, treatment of the monolayers for 24 h with thrombin or
      TRAP significantly decreased the electrical resistance and increased the
      permeability to mannitol and albumin. In addition, these treatments enhanced the
      appearance of actin stress fibers, and small gaps became visible at areas of cell
      cell contact. Thrombin appears to increase epithelial permeability by receptor
      mediated reorganization of the actin network in airway epithelial cells. This is
      likely to contribute to the impairment of the airway barrier function.

PMID- 16282713
TI  - A structure-based expert model of the ICD-10 mental disorders.
AB  - BACKGROUND: Many authors have highlighted that a classificatory system such as
      the ICD-10 or the DSM-IV should attempt to integrate categorical as well as
      dimensional aspects rather than relying only on a categorical distinction.
      METHODS: In the current study, a method is presented that allows both
      perspectives to be considered. Based on their clinical experience, 20 therapists
      were asked to rate a selection of ICD-10 mental disorders in terms of their
      similarity. The resulting data were processed by nonmetric multidimensional
      scaling on individual basis as well as mean basis and a cluster analysis.
      RESULTS: From a categorical point of view, the resulting mean cognitive map and
      the cluster analytic groups showed a good concordance with the ICD-10 F groups.
      Additionally, analogies to the critical observations with regard to the
      classification systems could be observed. From the dimensional point of view,
      there were two dimensions found (cognition and psychosis) which showed high
      correlations in the mean map. CONCLUSIONS: The method presented in this study
      offers an opportunity to account for dimensional as well as categorical aspects
      of classification by exploring the structure of the ICD-10 mental disorders
      directly from the point of view of therapists and thus creating the basis for an
      expert model.

PMID- 16282714
TI  - Why do people injure themselves?
AB  - The aim of this study was to evaluate a questionnaire for the assessment of
      immediate functions of self-injurious behavior (SIB). SIB is defined as
      deliberate injuries of the skin such as burning, cutting or beating. Suicidal
      attempts as well as self-injuries for aesthetic reasons were excluded. Immediate
      functions were collected from the literature as well as from statements of SIB
      sufferers. Finally, 154 questions with the response options 'right', 'wrong' and
      'unknown' -- for phenomena people did not know -- were given to 120 persons with
      SIB aged 13-54 years. They were recruited from SIB-related homepages as well as
      from psychologists and psychiatrists in hospitals in Austria and Germany. Twelve
      factors were extracted via factor analysis (varimax rotation): 'self-punishment',
      'coping with emotions', 'extreme rage', 'vitality', 'dissociation', 'changed
      perception', 'control over body', 'uniqueness', 'interaction', 'addiction',
      'coping with sexuality' and 'expression of sexuality'. All items of each factor
      were analyzed and unsatisfactory ones excluded to devise a questionnaire as short
      as possible but with high expressiveness and good reliability. The remaining 107
      items have a reliability of r = 0.9118 (Cronbach's alpha). Evaluation of this
      questionnaire is in progress.

PMID- 16282715
TI  - Impact of temperamental mood lability on depressive mixed state.
AB  - BACKGROUND: Cyclothymic temperament (which includes mood lability) is common in
      bipolar II disorder (BP-II). Depressive mixed state (DMX), a major depressive
      episode (MDE) mixed with intra-episode hypomanic symptoms (3 or more, according
      to a recently validated definition), was found to be common in BP-II and not
      uncommon in major depressive disorder (MDD). The study aim was to find the impact
      of temperamental mood lability (TML) on DMX. METHODS: Consecutive 148 BP-II and
      117 MDD outpatients presenting for MDE treatment were interviewed by the
      Structured Clinical Interview for DSM-IV as modified by Benazzi and Akiskal to
      reduce the false negative BP-II. Intra-MDE hypomanic symptoms were systematically
      assessed. Kraepelin, Angst, and Akiskal's definitions of temperamental mood
      lability (i.e., frequent up and down fluctuations of mood between major mood
      episodes since young age) were followed. RESULTS: DMX was present in 61.5%, TML
      in 52.8%. In the DMX sample, TML was present in 57.6%, and in the non-DMX sample
      TML was present in 45.0% (OR = 1.6, 95% CI = 1.0-2.7). In the DMX sample,
      independent predictors of DMX with TML were BP-II and young age at onset. Intra
      MDE hypomanic symptoms, and MDE, melancholic and atypical symptoms were not
      significantly different between DMX patients with TML and DMX patients without
      TML, apart from more temperamental interpersonal sensitivity in DMX patients with
      TML (OR = 2.0, 95% CI = 1.0-3.8). DISCUSSION: DMX patients with TML had a younger
      onset age, suggesting that TML may facilitate the onset of DMX or that it may be
      a precursor of DMX. The association of BP-II with DMX, TML, and interpersonal
      sensitivity can make the course of BP-II more unstable and its treatment more
      complex.

PMID- 16282716
TI  - Biogenetic temperament and character and attention deficit hyperactivity disorder
      in Korean children.
AB  - BACKGROUND: The objective of this study was to evaluate the relationship between
      symptoms of attention deficit hyperactivity disorder (ADHD) and biogenetic
      temperament, as assessed by the Junior Temperament and Character Inventory (JTCI)
      in Korean elementary school children. SAMPLING AND METHODS: Five hundred and
      sixteen elementary school students (254 boys and 262 girls; age range 9-14 years,
      mean age 11.0 +/- 1.0 years) were studied. The Junior Temperament and Character
      Inventory, both the self-rating and parent rating scales, the DuPaul ADHD rating
      scale (ARS-IV) for parents and teachers and the Child Behavior Checklist have
      been completed by study subjects. Children with high ARS-IV scores (the upper
      10th percentile, n = 52) were defined to have ADHD. Fifty-two age- and sex
      matched non-ADHD control subjects were selected randomly from a pool of 464
      subjects. RESULTS: Inattention and hyperactivity/impulsivity symptoms correlated
      positively with Novelty Seeking in both children and parent ratings. These
      symptoms correlated negatively with Persistence, Self-Directedness and
      Cooperativeness. Novelty Seeking also had significant correlations with attention
      problems, delinquent behavior, aggressive behavior, externalizing problems and
      social problems in the Child Behavior Checklist. The ADHD group (n = 52) had
      higher scores of Novelty Seeking and lower scores of Self-Directedness and
      Cooperativeness, compared with the control group. CONCLUSIONS: There were
      significant correlations between ADHD symptoms and Novelty Seeking. Current
      findings suggest that Novelty Seeking and ADHD share biogenetic backgrounds.

PMID- 16282717
TI  - Investigation of the syndrome of apotemnophilia and course of a cognitive
      behavioural therapy.
AB  - BACKGROUND: The syndrome of apotemnophilia, body integrity or amputee identity
      disorder, is defined as the desire for amputation of a healthy limb, and may be
      accompanied by behaviour of pretending to be an amputee and sometimes, but not
      necessarily, by sexual arousal. SAMPLING AND METHODS: A case history is presented
      of a 35-year-old man who was referred because of his desire for amputation of his
      left leg, without sexual connotations. The course of a combined cognitive
      behavioural psychotherapy with SSRI treatment is described. RESULTS: Symptoms
      showed considerable similarity with obsessive-compulsive disorder, and some
      similarity with body dysmorphic disorder according to DSM-IV, but the core
      symptom seemed to be strongly connected with a sense of identity. Treatment with
      a selective serotonin re-uptake inhibitor decreased levels of distress only. The
      effects of cognitive restructuring of the psychotherapy were limited, whereas the
      behavioural elements substantially reduced the behaviour of pretending to be an
      amputee. CONCLUSIONS: The rare syndrome of apotemnophilia raises unresolved
      questions of classification. Psychotic disorders should be ruled out carefully.
      The model designed in the current cognitive behavioural approach may serve as a
      starting point for further development of intervention protocols for this rare
      disorder.

PMID- 16282718
TI  - Vocalisation in verbal hallucinations: case report and theoretical model.
AB  - Perception of one's speech or the speech of others reflects an intrinsic process
      and should not to be seen as a product of information processing of external
      sensory input. From this perspective, the perception of one's own or others'
      speech is fundamentally equivalent to the experience of verbal hallucinations.
      Speech perception is generated primarily in the focus of attention, but auditory
      and proprioreceptive input from verbal articulations play an important
      constraining role, ensuring that perception remains adaptive to interaction with
      the external world. In verbal hallucinations these constraints may be partially
      disrupted. Perceptual qualities of hallucinatory voices may be generated in the
      focus of attention alone (in ignorance of actual acoustic stimulation from the
      environment), whilst content and grammatical aspects of hallucinatory speech
      perception may continue to be constrained adequately by proprioreceptive
      reafferentation from the speech apparatus. Thus subvocal speech may play a role
      in the elaboration and maintenance of verbal hallucinations.

PMID- 16282719
TI  - Delusions or obsessions: the same only different? A case report.
AB  - The phenomenological distinction between delusions and obsessions has been the
      subject of much debate in psychiatry. Some authors feel these symptoms are
      distinct nosological entities, while others argue that they reflect
      manifestations of the same symptom and are distinguishable on the basis of the
      level of insight a patient displays. In this report we describe the case history
      of a lady who presented with an obsessional disorder. The symptom was resistant
      to standard treatments and subsequently became more delusional in nature. We
      review the literature in terms of the classification of obsessions and delusions
      and offer assistance to clinicians in terms of the diagnosis and treatment of
      cases where the distinction between these phenomena is not clear and offer
      alternative means of classifying these symptoms based on insight.

PMID- 16282720
TI  - [Molecular targeted therapy--non-small-cell lung cancer and gefitinib].
AB  - Gefitinib (Iressa, ZD 1839) is an orally bioavailable small molecule that
      selectively inhibits epidermal growth factor receptor(EGFR) tyrosine kinase
      activity. Gefitinib causes a dramatic response in approximately 10% to 20% of
      patients with non-small-cell lung cancer (NSCLC) who receive prior chemotherapy.
      Studies of gefitinib in combination chemotherapy in first-line therapy of
      advanced NSCLC have, however, failed to show improvement of survival. Gefitinib
      also failed to prolong survival in a placebo controlled clinical trial for
      patients with pretreated advanced NSCLC. In addition, gefitinib did not improve
      survival as maintenance therapy after chemoradiation in patients with Stage III
      NSCLC. A possible explanation for the lack of a survival benefit seen in these
      studies might be failure to select of patients suitable for gefitinib treatment.
      Empirically, and also in phase II trials, a good clinical response has been
      observed most frequently in women, nonsmokers, patients with adenocarcinomas, and
      East Asian patients. Recently, mutations and amplifications of the EGFR gene
      identified in a subset of NSCLC have been reported to be useful for prediction of
      enhanced sensitivity to gefitinib. It is also known that some recurrent tumors
      have a secondary mutation in the EGFR kinase domain, T 790 M, conferring drug
      resistance. In Japan, a significant number of patients often develop fatal
      interstitial lung disease after the introduction of gefitinib, although it is, in
      general, well tolerated. In the future, we must demonstrated benefits of
      gefitinib treatment in prospective clinical trials by recruiting patients
      selected on the basis of biological characteristics. It is also important to
      further elucidate various issues that include other determinants of gefitinib
      sensitivity, other mechanisms of resistance to gefitinib or mechanisms or
      predictive factors of interstitial lung disease by close collaboration among
      clinicians and basic researchers.

PMID- 16282721
TI  - [Pharmacogenomic data for personalized medicines].
AB  - FDA issued guidance for industry regarding pharmarcogenomic data submission this
      year. Polymorphic cytochrome P450 2D6 and thiopurine S-methyltransferase in
      patients are now considered biomarkers for drugs which are predominantly
      metabolized by these enzymes. This article reviews current efforts to treat
      pharmacogenomic data for new drug development and personalized medicines.

PMID- 16282722
TI  - [Exploration of novel molecular targets for cancer therapy based on genomic
      aberrations].
AB  - Tumors develop through the combined processes of genetic instability and
      selection, resulting in clonal expansion of cells that have accumulated the most
      advantageous set of genetic aberrations. Many types of instability may occur,
      resulting in point mutations, chromosomal rearrangements, DNA dosage
      abnormalities, and epigenetic changes such as methylation. In order to identify
      novel molecular targets for cancer therapy, we have focused on genomic copy
      number aberrations as landmarks. Recent advances in array-based CGH technology
      (CGH-array) have enabled examination of chromosomal regions in unprecedented
      detail, prompting us to screen cancer-related genes including candidates of
      molecular targets. Indeed, applying our in-house CGH-array, we have identified
      several amplification target oncogenes as well as tumor suppressor genes. Useful
      molecular targets for cancer therapy will be identified more rapidly through
      exploring genomic and/or epigenomic abnormalities using genomic arrays including
      CGH-array system.

PMID- 16282723
TI  - [Genetic alterations and chemoresistance].
AB  - Molecular targeting agents will likely play an increasing role in the management
      of cancer.However, resistance to anti-neoplastic drugs remains a serious obstacle
      to successful cancer treatment. Analysis of SNPs and microarray technologies
      should enable us to predict toxic responses and sensitivities to anticancer
      agents of each patient, and the prediction may permit patient-specific anticancer
      agents and dosages that reduce the risk of acute toxicity and emergence of drug
      resistant tumors. The relationships are reviewed between the
      chemoresistance(chemosensitivity) and polymorphisms, tumor gene expression
      profiles or mutations of targeted molecules that confer resistance to molecular
      target therapy.

PMID- 16282724
TI  - [Polygenetic pharmacogenomic strategies to identify drug sensitivity biomarkers].
AB  - Pharmacogenomics is a large-scale systematic approach using a variety of genomic
      technologies to discover drug response determinants and promote a better
      understanding of the genetic and molecular basis underlying variable drug
      response among patients. However, few critical prediction markers of drug
      response have been validated to date. Drug sensitivity is determined by multiple
      genes:drugs are often involved in complex metabolic pathways before they produce
      anti-cancer activity, and the related genes do not act in isolation. Although the
      worldwide research on the human genome exerts a major impact on medical science
      and advanced medicine, the detailed function and interaction of most genes remain
      unclear. There is clear evidence that a variety of genes are closely associated
      with cellular drug sensitivity, but most of the regulatory mechanisms of their
      expressions are poorly understood. To understand the drug sensitivity mechanism
      and identify the key biomarkers, recent attention has focused on the
      transcriptional mechanisms of drug sensitivity genes and their network. These
      approaches in genome research and the functional analysis may revolutionize the
      anticancer chemotherapy world. The possible contribution of new challenges and
      problems of the day were reviewed while showing recent findings on the analyses
      of 5-FU metabolic pathway and the key gene DPYD as an example.

PMID- 16282725
TI  - [SNPs associated with adverse effects].
AB  - In recent years, pharmacogenomics have received much attention from the increased
      expectations for so-called order-made medicine. It is experientially clear that
      inter-individual differences exist in the degree of efficacy and occurrence of
      adverse effects. These inter-individual differences are observed not only among
      anticancer chemotherapeutics but in almost all drugs. Several studies have
      revealed that genetic factors are involved in these inter-individual differences.
      To date, the relationships have been revealed between adverse effects of some
      anticancer drugs and polymorphisms of drug metabolizing genes. Such relationships
      include 5-FU and DPYD gene, methotorexate and MTHFR gene, irinotecan and UGT 1A1
      gene and 6-MP and TPMT gene. By using information on these polymorphisms, it will
      be possible to predict the occurrence of adverse effects before using anticancer
      drugs. In particular, information on polymorphisms related to the possibly
      adverse effects of irinotecan is now given in its package leaflet. This means
      that order-made medicine is a step closer. In this review, we discuss the
      relationships between polymorphisms of genes and the adverse effects of
      anticancer drugs. Furthermore, we want to suggest the direction of further
      pharmacogenomic studies with an eye to the realization of order-made medicine.

PMID- 16282726
TI  - [Weekly docetaxel treatment for head and neck cancer].
AB  - A pilot study was conducted to evaluate the safety and efficacy of weekly
      docetaxel(DOC) treatment for head and neck cancer as compared with those of 3
      weekly DOC treatment at 60 mg/m(2). Weekly DOC was administered at doses ranging
      from 25-30 mg/m(2)/wk (mean dosage, 40 mg/body/wk) for 3 weeks followed by a 1
      week rest or for 6 weeks followed by a 2-week rest. Weekly DOC was administered
      to 18 patients (1 of whom received prior chemotherapy), and 3-weekly DOC was
      administered to 29 patients (10 of whom received prior chemotherapy). The overall
      response rate was 22.2% in the weekly DOC group and 47.8% in the 3-weekly DOC
      group. In advanced or recurrent cancer, the overall response rate plus long NC
      (stable disease for at least 6 months) rate was 40.0% in the weekly DOC group,
      and 42.9% in the 3-weekly DOC group. Only 1 (5.6%) case of grade 3 mucositis
      developed in the group receiving weekly DOC, while 12 cases of grade 3 or 4
      neutropenia (41.4%) and 2 of grade 3 or 4 thrombopenia (6.9%) developed in the 3
      weekly DOC group. Based on these results, weekly DOC treatment appears to be
      useful and feasible for outpatients with head and neck cancer, even in high-risk
      and elderly patients.

PMID- 16282728
TI  - Changes in hepatic parenchymal ultrasound images in tamoxifen medication
      patients.
AB  - We experienced changes in ultrasonographic features of hepatic parenchyma in 156
      patients treated with Tamoxifen (TAM) as an adjuvant hormonal therapy for breast
      cancer. After the treatment with TAM subsequent to the surgery for breast cancer,
      36% of patients showed changes in ultrasonographic features of the liver more
      than Grade 2, despite no obvious hepatic involvement at the start of the
      medication. Forty-five percent of affected patients showed Grade 2 or 3 changes
      in hepatic parenchymal images within the first 6 months of TAM medication, while
      the average interval of change was 11.3 months. Abdominal ultrasound inspection
      should be undertaken within 6 months of surgery to aid the early detection of
      liver metastasis and fatty liver changes, which may play an important role in
      determining postoperative follow-up care for breast cancer patients.

PMID- 16282727
TI  - [The feasibility of FEC (75) as adjuvant chemotherapy for Japanese breast cancer
      patients].
AB  - Recently, high-dose FEC (fluorouracil, epirubicin, and cyclophosphamide) has been
      increasingly used in adjuvant chemotherapy for breast cancer in Japan. However,
      the safety and tolerability of high-dose FEC are not well evaluated in Japanese
      breast cancer patients. We studied the feasibility of FEC (75) (fluorouracil: 500
      mg/m(2), epirubicin: 75 mg/m(2), and cyclophosphamide:500 mg/m(2), q 3 w, 6
      cycles) as adjuvant chemotherapy for 59 primary breast cancer patients. Out of
      these patients, 56 (94.9%) finished 6 cycles-FEC. The mean epirubicin dose
      received was 431.7 mg/m(2) (95.9% of the intended dose of 450 mg/m(2)). Forty
      five (76.2%) of 59 patients experienced neutropenia of grade 3 or 4, while the
      rates of febrile neutropenia (grade 3) and infection (grade 2) were 3.4% and
      10.2%, respectively. Anemia (88.2%), fatigue (42.4%), nausea (40.6%), liver
      dysfunction (40.7%), and vomiting (18.7%) occurred, however most of them were
      mild and categorized into grade 1 or 2. No patients developed any cardiac failure
      symptoms. This study shows FEC (75) is well tolerable as adjuvant chemotherapy
      for Japanese breast cancer patients.

PMID- 16282729
TI  - [Expression of mRNA levels of thymidylate synthase, dihydropyrimidine
      dehydrogenase, and orotate phosphoribosyltransferase of colorectal cancer-
      relationships among mRNA levels in association with response to 5-FU based
      treatment].
AB  - We semiquantificated the mRNA levels of thymidylate synthase (TS),
      dihydropyrimidine dehydrogenase (DPD), and orotate
      phosphoribosyltransferase(OPRT) from the frozen tissue of colorectal cancer, in
      order to examine the relationships among these enzymes and the efficacy for 5
      fluorouracil (FU)-based treatment in terms of the combinations of the expression
      levels of these enzymes. There were weak and positive relationships among TS mRNA
      expression and OPRT mRNA expression or DPD mRNA expression, while there was no
      significant relationship between DPD mRNA expression and OPRT mRNA expression (n
      = 112). In 39 patients who received 5-FU-based chemotherapy with evaluable
      lesions, patients with low TS expression (n = 23) showed a higher response rate
      (52%) as compared to those with high TS expression (13%, p = 0.02). Patients with
      low TS, low DPD, or high DPD expression tended to show a higher response rate
      (50%) than those with the other combinations (26%, p = 0.09). In addition, all of
      the responders with only one favorable factor (n = 4) were associated with low TS
      or low DPD expression. In conclusion, low TS expression followed by low DPD
      expression is important to predict the efficacy of 5-FU-based treatment for
      colorectal cancer. However, it may be of little significance to semiquantify the
      expression of OPRT.

PMID- 16282730
TI  - [Efficacy of tegafur/uracil plus oral leucovorin therapy for advanced or
      recurrent colorectal cancer].
AB  - The aim of this study was to evaluate the efficacy of tegafur/uracil (UFT) and
      oral Leucovorin(UZEL) in patients with advanced or recurrent colorectal cancer.
      Eight patients were treated with UFT/UZEL therapy as a first-line chemotherapy.
      UFT(300 mg/m(2)/day) and UZEL (75 mg/body/day) were administered orally for 28
      consecutive days followed by a 7-day rest period, and this schedule was repeated
      every 5 weeks. The mean of treatment courses given to the patients was 7.6. Tumor
      response was evaluated in 7 patients who had assessable lesions, and the response
      rate was 86% (6 PR and 1 NC). Adverse reactions of grade 3 were observed in 2
      patients (25%), but toxicity did not cause a discontinuance of treatment in any
      case. The UFT/UZEL therapy was considered to be a promising regimen for advanced
      or recurrent colorectal cancer from a standpoint of effect, safety and QOL of
      patients.

PMID- 16282731
TI  - [A case of Giant GIST of the stomach successfully treated with imatinib mesylate
      neoadjuvant therapy and followed postoperatively].
AB  - Since the advent of imatinib mesylate (IM), its clinical efficacy against
      gastrointestinal stromal tumor (GIST) has been widely acknowledged, and
      therapeutic strategies for this disease have undergone great changes. We recently
      experienced a case of giant GIST of the stomach that was successfully treated
      with IM neoadjuvant therapy prior to surgical resection, but liver metastasis
      recurred 1 year and 7 months after the operation. The patient was a 65-year-old
      male who presented at our department with the chief complaints of dizziness,
      malaise, and fever in April 2002. An abdominal CT revealed a mass with a maximum
      diameter of 17 cm, as well as a cystic septate mass, 12 cm in diameter, with a
      thick capsule in the left lobe of the liver. The patient was diagnosed with GIST
      of the stomach and liver metastasis. Since radical operation was considered
      difficult at that point, IM (400 mg/day) was started on May 9. The result of
      treatment was determined to be PR, and radical operation was considered feasible.
      On March 18, 2003, total gastrectomy and left hepatic lobectomy/S 6 partial
      lobectomy were performed in the surgery department of our hospital. The
      postoperative course was favorable and oral administration of IM was resumed soon
      after the operation. However, the drug was discontinued for financial reasons and
      a decreased white blood cell count (grade 3) 2 months after the operation.
      Recurrence in the liver and abdominal wall was found in October 2004, and oral
      administration of IM was resumed again. Currently, treatment with IM is ongoing.
      Case reports on the efficacy of IM neoadjuvant therapy are occasionally found in
      the literature, but there are few reports on its long-term prognosis. We report
      this case with a discussion of future therapeutic options.

PMID- 16282732
TI  - [A case of advanced gastric cancer with direct invasion of the transverse colon
      responding to paclitaxel/5'-DFUR combined therapy].
AB  - A 50-year-old man was diagnosed with non-resectable scirrhous gastric cancer of
      antrum accompanied with colon ileus due to direct invasion of the transverse
      colon. As the ileus improved after cecostomy, chemotherapy with TS
      1/cisplatin(CDDP) was performed. Because of no response, 4 cycles of paclitaxel
      (PTX)/doxifluridine (5'-DFUR) therapy was performed as second-line chemotherapy.
      Since the stenosis of transverse colon dilated completely and the tumor
      disappeared, we performed total gastrectomy and right hemicolectomy, and could
      resect completely. Though 2 cycles of PTX/5'-DFUR therapy was performed
      postoperatively and the patient's postoperative condition was good, he was
      suffering from carcinomatous peritonitis complicated by ileus and obstructive
      jaundice 4 months after operation. He died 1 year after the first medical
      examination, but his QOL was fairly good for 10 months. PTX/5'-DFUR therapy,
      which has only slight complications, may be useful for patients with recurrent
      gastric cancer who had been treated with 5-FU administration as first-line
      chemotherapy. But the future problem was how to control dissemination after
      surgery in a resectable case after chemotherapy.

PMID- 16282733
TI  - [A case of cecal cancer with multiple liver metastases responding to irinotecan
      (CPT-11)/cisplatin (CDDP) combination therapy for elevation of CA19-9 after
      complete response (CR) by l-leucovorin(LV)/5-fluorouracil(5-FU) therapy].
AB  - A 62-year-old woman complained of abdominal pain and diarrhea from February 2,
      2002. She was diagnosed with advanced cecal cancer with simultaneous multiple
      liver metastases. The serum level of CA 19-9 was 420 U/ ml. Ileoceal resection
      with D3 lymphnode dissection. The replacement of reservoir for hepatic arterial
      infusion (HAI) was performed on February 2, 2002. As the dissemination was seen
      near the mesocolon at laparotomy, we could resect all together. Pathological
      examination demonstrated II, 5.0 x 2.5 cm, mod, se, INFgamma, ly(1), v(1), n(2),
      stage IV. Systemic l-leucovorin/5-fluorouracil (l-LV/5-FU) + HAI of weekly high
      dose 5-FU combination therapy was initiated at postoperative 14 days. The serum
      CA 19-9 level decreased immediately but was not within the normal range. On
      abdominal computed tomography (CT), liver metastatic lesions decreased 9 9% on
      May 27, 2002 and disappeared on August 26, 2002. Though there were no signs of
      recurrence, the serum CA 19-9 level elevated as of October, 2002. Since the
      hepatic artery was occluded, HAI was discontinued on November 28, 2002. The serum
      CA 19-9 level elevated inspite of the continuation of the l-LV/5-FU therapy which
      we increased an amount of 5- FU. Thus, we changed low-dose irinotecan (CPT
      11)/cisplatin (CDDP) therapy. The serum level of CA 19-9 decreased gradually and
      got with in normal range on March, 2004. It did not elevate since then. Low-dose
      CPT-11/CDDP therapy may be useful for patients with advanced colon cancer thought
      to be resistant to 5-FU as second-line chemotherapy.

PMID- 16282734
TI  - [A case of primary small intestinal cancer accompanied by virchow lymph node
      metastasis undergoing TS-1 treatment].
AB  - A 72-year-old female was admitted to our hospital with the complaint of left neck
      lymph node swelling. Abdominal computed tomography (CT) revealed wall thickening
      of the small intestine and multiple lymph node metastases. Barium meal study of
      the small intestine showed circular stenosis. The patient was operated on under a
      diagnosis of tumor of the small intestine and left neck lymph node swelling.
      Needle biopsy of the left neck lymph node and partial resection of the small
      intestine was done without regional lymph node dissection because of Virchow
      lymph node metastasis. On the resected material a 5 x 4 cm type 2 tumor was
      identified. Pathological findings included poorly-differentiated adenocarcinoma,
      si (bladder), n 4, P 0, ly 3, v 3, H 0, M(-), Stage IV. The patient received the
      chemotherapy with TS-1. TS-1(80 mg/body/day) orally administered for 4 weeks
      followed by a drug-free 2-week period as one course. CT revealed that the
      metastatic lesion had shrunk markedly after the second course. A complete
      response (CR) was observed after one year. There were no drug side effects. At
      present, 3 years and 9 months after the operation, cervical and abdominal CT
      reveals no evidence of enlargement of the cervical and intraperitoneal lymph
      nodes.

PMID- 16282736
TI  - [A clinical study of hepatic arterial infusion chemotherapy with low-dose CDDP
      and 5-FU for liver metastases].
AB  - We followed patients who underwent hepatic arterial infusion chemotherapy with
      low-dose CDDP+5-FU for liver metastases from colorectal cancer in the outpatient
      setting. A catheter was inserted from the femoral artery into the proper hepatic
      artery using the interventional technique. Two complete response (CR) and seven
      partial response (PR) were achieved, but later 2 of these patients had lung
      metastases. We conclude that this therapy may be effective, but control of
      extrahepatic lesions is necessary for life prolongation.

PMID- 16282735
TI  - [A case of multiple hepatic and peritoneal metastases from colon cancer
      responding to oral UFT+leucovorin chemotherapy].
AB  - A 57-year-old woman underwent right hemicolectomy (D3) due to transverse colon
      cancer with multiple liver and peritoneal metastasis. Administration of oral
      UFT+Leucovorin was started postoperatively. After 6 months, the multiple liver
      metastases completely disappeared without any adverse reaction. After 14 months,
      no other recurrence was found by CT scan. This case suggests the usefulness of
      oral UFT+Leucovorin for progressive recurrent colorectal cancer as home
      chemotherapy.

PMID- 16282737
TI  - [A case of multiple lung metastases of sigmoid colon cancer responding well to
      oral UFT+leucovorin therapy].
AB  - Chemotherapy combining 5-fluorouracil (5-FU) with leucovorin is now used as a
      standard regimen for chemotherapy of inoperative, recurrent or distantly
      metastasized colorectal carcinoma. We recently treated a patient with multiple
      metastases of sigmoid colon cancer by sigmoidectomy and oral drug therapy using a
      combination of Uzel (dl-leucovorin) and UFT (uracil and tegafur). Three courses
      of this therapy were administered, with each course consisting of treatment for 4
      consecutive week (UFT 400 mg/day, Uzel 75 mg/day) and a one week interval between
      successive courses. The therapy resulted in marked reduction of tumor and this
      response was rated as PR (partial response). The lower lobe of the right lung,
      which showed the largest tumor (34.5 x 35.7 mm), was resected, and the upper lobe
      of the same lung, showing a small metastastic tumor (4.4 x 4.6 mm), was partially
      resected. Oral chemotherapy, which had begun before surgery, was continued after
      lobectomy and partial pneumonectomy. To date (January 15, 2005), the patient has
      received 5 courses of this therapy and has shown no signs of tumor exacerbation.
      Because this therapy has allowed satisfactory control of metastatic tumor for
      about one year since surgery without causing any adverse reaction or requiring re
      hospitalization, it is fair to say that the therapy has successfully maintained
      the quality of life (QOL) of this patient.

PMID- 16282738
TI  - [A case of rectal cancer treated by preoperative chemoradiation].
AB  - Fifty-one-year-old male visited our hospital suffering from anal pain and
      subileus. Further examination revealed that advanced rectal cancer which invaded
      to presacral space (Ai, N 0, P 0, H 0, M(-), stage IIIa) caused such symptom. We
      administered neo-adjuvant chemoradiotherapy for fear of non curative resection of
      the rectum. The regimen was once weekly administration of intravenous CPT-11 40
      mg, plus daily oral administration of UFT-E 600 mg/day and Uzel 75 mg/day for 4
      weeks. In addition we underwent radiation 2.4 Gy/day and intravenous low-dose
      cisplatin (CDDP) 5 mg/day, 5 days/week for 3 weeks. Four weeks after the first
      administration, a partial response was confirmed on CT, and so we carried out an
      abdominoperineal resection. The postoperative course is almost uneventful without
      a little perineal infection. The specimen revealed that no malignant lesion
      remained, which changed to necrotic tissue. The side effects were not so severe.
      For example, diarrhea, nausea, and mucosal dysfunction were each less than grade
      2, and there was much tolerate for renal, liver, and bone marrow function. This
      combination chemoradiotherapy is considered to be effective for locally advanced
      rectal cancer.

PMID- 16282739
TI  - [Complete disappearance of metastatic lung tumors and mediastinal lymphnode in a
      case of hepatocellular carcinoma treated by low-dose 5-fluorouracil/cisplatin
      therapy].
AB  - We report a case of complete disappearance of multiple lung metastases and
      mediastinal lymphnode metastasis by intravenous administration of 5
      fluorouracil/cisplatin (FP) after operation for primary hepatocellular carcinoma
      (HCC). A 54-year-old male was diagnosed with HCC associated with alcoholic liver
      cirrhosis. He also had a single lung metastasis at the time of diagnosis. After
      hepatic resection for HCC, the metastatic tumor progressed and became multiple
      lesions with mediastinal lymphnode involvements. Low-dose FP therapy was
      performed. Then, 250 mg/m(2)/day of 5-fluorouracil was given intravenously for 5
      days weekly by continuous infusion and 10 mg/m(2)/day of cisplatin by intravenous
      infusion. Both lung metastases and mediastinal lymphnode metastasis were
      decreasing after six cycles of this therapy. Because of alcoholism and liver
      damage, chemotherapy could not be continued. But all metastatic lesions were
      completely disappeared ten months after this therapy. Bone marrow suppression
      (grade 4) was observed during the chemotherapy but resolved by interruption of
      treatment. Low-dose FP therapy may well be useful for patients suffering from
      advanced HCC with distant metastasis.

PMID- 16282740
TI  - [A case of pancreatic cancer complicated by gemcitabine-induced peripheral
      edema].
AB  - Gemcitabine mono-therapy was carried out in an unresectable pancreatic cancer.
      After six courses of treatment, pitting edema appeared and gradually became worse
      especially after gemcitabine infusion. Gemcitabine-induced edema was suspected
      after exclusion of other causes. Diuretics and steroids were useful to control
      the peripheral edema in this case, and gemcitabine therapy could be continued.

PMID- 16282741
TI  - Gefitinib for previously untreated patients with non-small cell lung cancer
      (NSCLC)--a retrospective study of 12 patients treated in one institution.
AB  - Gefitinib has a modest activity in previously treated patients with advanced non
      small cell lung cancer (NSCLC). However, the efficacy and safety of gefitinib
      monotherapy in untreated advanced NSCLC is not known. We retrospectively reviewed
      the records of 12 patients of NSCLC who were unfit or refused cytotoxic
      chemotherapy, and were treated with a single-agent gefitinib as first-line
      therapy in our hospital. The patients were 6 males and 6 females. The median age
      was 76.5 years (range 34-82). The histological types were adenocarcinoma in all
      patients. Clinical stage was IIB in one patient, IIIB in four, and IV in seven.
      Five were elderly patients and four were patients with ECOG PS (performance
      status) 3. Five had partial response (PR), and two had stable disease (SD). The
      response rate was 41%. The median time to progression (TTP) was 126 days. Grade 1
      diarrhea was observed in three patients, grade 1 or 2 eruption paronychia was in
      eight, and grade 1 or 2 liver dysfunction was in two. No grade 3 or 4 toxicities
      occurred. Gefitinib monotherapy may provide an opportunity for untreated NSCLC,
      particularly unsuitable patients with standard chemotherapy. Prospective studies
      of gefitinib monotherapy as first-line treatment are warranted.

PMID- 16282742
TI  - [Thymic cancer effectively treated by combination chemotherapy of carboplatin and
      etoposide with concurrent radiotherapy].
AB  - A 63-year-old man was admitted to our hospital for acute heart failure. A chest
      CT scan revealed a large anterior mediastinal mass and pericardial effusion.
      Percutaneous needle biopsy showed that the mass was an advanced thymic cancer
      (squamous cell carcinoma). The patient was treated by combination chemotherapy of
      carboplatin and etoposide with concurrent radiotherapy (44 Gy). There was no
      severe toxicity except for grade 4 neutropenia. After 3 courses of chemotherapy,
      the mass showed an approximately 81% reduction in tumor size and disappearance of
      the pericardial effusion. Finally, the thymic cancer and small pulmonary
      metastatic lesions were all resected. This concurrent chemoradiotherapy can be
      effective against inoperable squamous cell carcinoma of the thymus.

PMID- 16282743
TI  - [Temporary effective treatment with L-asparaginase for a patient with refractory
      nasal NK/T-cell lymphoma].
AB  - A 48-year-old man was referred to Sakai Municipal Hospital with nasal discharge
      and right facial swelling. The pathological findings of a nasal cavity tumor
      revealed stage IIB NK/T-cell lymphoma. He was admitted to our hospital and
      received CHOP therapy, resulting in progressive disease. Irradiation therapy
      combined with DeVIC chemotherapy also could not shrink his lymphoma. Then, two
      courses of L-asparaginase(L-Asp) were administered, resulting in partial
      improvement of the nasal and pharynx lesions, resolution of the fever and
      improvement of his performance status. On the day before a third course of L-Asp,
      he again developed a lowgrade fever. Although L-Asp was administered for several
      days, marked elevation of serum LDH, AST, ALT level, and thrombocytopenia
      persisted, and he died. Post-mortem examinations revealed hemophagocytosis in the
      bone marrow and liver, and infiltration of lymphoma cells into multiple organs
      including left lower lung, liver, spleen and kidneys. Although L-Asp was
      effective against nasal NK/T-cell lymphoma resistant to combination chemotherapy
      and irradiation therapy, the effectiveness of the single agent with L-Asp was
      only transient. L-Asp based regimen should be used as first-line therapy if
      asparagine synthetase protein expression is low using an immunohistochemical
      method.

PMID- 16282744
TI  - [The opioid combination of transdermal fentanyl and sustained release morphine
      for refractory cancer pain--a case report].
AB  - Transdermal fentanyl (TDF) has been increasingly administered for the management
      of cancer pain. Occasionally, some patients fail to obtain poor analgesic effects
      with its dose escalation. We discuss a case of a 44-year-old male diagnosed with
      lung cancer with back pain caused by bone metastasis. He was administered a TDF
      of 75 microg/hr with good pain relief on admission. With time, the dose
      escalation to 300 microg/hr induced neuroexcitatory adverse effects without pain
      improvement. The conversion to 150 microg/hr TDF and sustained-release oral
      morphine 360 mg/day provided effective pain control. This clinical phenomenon
      demonstrated a possible association with the development of opioid tolerance.
      Although several experimental approaches regarding partial opioid substitution or
      combining different opioids for better pain control were suggested, the basic
      studies of opioid tolerance do not justify conclusions. In this case, partial
      opioid rotation and opioid combination were beneficial approaches to pain
      management.

PMID- 16282745
TI  - How to help Acehnese helping themselves?--a note after a visit with Kobe
      University medical team.
AB  - On December 26, Aceh Province in Indonesia was hit by the worst earthquake and
      tsunami. A medical team from Kobe University Graduate School of Medicine visited
      two of the affected areas on the eastern coast of Aceh: Sigli and Lhokseumawe.
      This article provides a simple description of experience and assessment derived
      from the visit. The disaster has left Indonesia with complex problems, which will
      take a long time to overcome. A continuity of the aid and assistance from various
      resources is crucial to help Indonesia rebuilt the affected areas. These
      continuous efforts will provide great contribution for Acehnese people to recover
      and rebuild their life after tsunami.

PMID- 16282746
TI  - Brouhaha across the atlantic: decubitus ulcers defy description.

PMID- 16282747
TI  - Why a historical approach offers clinical benefits.

PMID- 16282748
TI  - PsEma--a hitherto unnamed dermatologic entity with clinical features of both
      psoriasis and eczema.
AB  - INTRODUCTION: Recent advances in molecular biology have helped establish
      differences between psoriasis and a group of inflammatory skin disorders commonly
      referred to as eczema. The authors have observed significant overlap between
      these two conditions such that a distinction between them may not always be made,
      even with histologic examination of skin biopsy specimens. OBJECTIVE: To
      determine how frequently psoriasis patients present features of both psoriasis
      and eczema. METHODS: The authors conducted a prospective analysis of 100
      consecutive psoriasis patients in their clinic. RESULTS: The authors found that
      20% could be diagnosed as "intermediate," having lesions with characteristics of
      both psoriasis and eczema, or a personal history of both. The authors suggest
      naming this category of inflammatory dermatosis "PsEma"--an overlap condition in
      which the clinical, histologic, molecular, biologic, and therapeutic responses
      show characteristics of both psoriasis and eczema.

PMID- 16282749
TI  - Activation markers in Behcet's disease.
AB  - INTRODUCTION: One of the main problems in Behcet's disease is the lack of an
      original laboratory marker that can reflect clinical activity. In this study,
      laboratory parameters that could be used as indicators of active disease are
      investigated. MATERIALS AND METHODS: The study included a total of 40 patients
      with Behcet's disease, 25 of whom were active and 15 inactive, who applied to
      Firat University, Firat Medical Center Dermatology, Rheumatology, Physiotherapy,
      and Ophthalmology outpatient clinics and a control group composed of 30 healthy
      volunteers. Serum neopterin, C-reactive protein (CRP), and sedimentation rate
      (ESR) levels were determined in all patients and healthy controls. RESULTS: Serum
      neopterin, CRP, and ESR levels in active Behcet's disease patients were
      significantly higher than those in both the inactive group and healthy controls
      (p<0.001). CONCLUSIONS: It was contemplated that together with serum CRP and ESR,
      neopterin could be a useful laboratory parameter in patients in whom disease
      activation could not be determined.

PMID- 16282750
TI  - Past and future: porphyria and porphyrins.
AB  - Porphyria is a compelling disease--disrupted enzyme pathways, heightened
      sensitivities, and a fascinating history tied in with tales of Dracula. This
      review discusses the history, pathophysiology, classification, and treatment of
      porphyria. It further discusses the way in which research on the etiologies of
      the various porphyrias has led to the development of porphyrin-based photodynamic
      therapy, which shows great promise in targeted therapy for a variety of serious
      pathologies.

PMID- 16282751
TI  - Arthritis and skin disease.
AB  - Skin lesions are frequently a harbinger of an underlying rheumatic disease or may
      be of great help in achieving the diagnosis of an underlying joint or connective
      tissue disease. For this reason, the evaluation of the skin is mandatory for the
      rheumatologist. In fact, the skin is the most accessible organ and often provides
      valuable diagnostic clues. Pattern recognition of skin lesions is based upon the
      type, configuration, distribution, and evolution of the lesions; selective
      laboratory techniques may further assist the diagnosis. This article focuses on
      the most relevant cutaneous disease in patients with rheumatic disease and
      emphasizes those characteristic features that will allow the clinician to
      identify cutaneous lesions that are commonly associated with musculoskeletal
      syndromes.

PMID- 16282752
TI  - Cutaneous squamous cell carcinoma in patients with chronic lymphocytic leukemia.
AB  - Patients with chronic lymphocytic leukemia are at heightened risk for the
      development of cutaneous malignancies, especially squamous cell carcinoma. These
      tumors portend a worse prognosis than is typically seen in immunocompetent
      patients. Patients with chronic lymphocytic leukemia who develop squamous cell
      carcinoma are more likely to develop multiple tumors, recurrences after
      treatment, and regional or distant spread of their tumor. Evaluation of the
      literature substantiates the ominous nature of squamous cell carcinoma in
      patients with underlying lymphocytic malignancies.

PMID- 16282753
TI  - Dermatophytosis: the management of fungal infections.
AB  - Dermatophytosis is an infection of the hair, skin, or nails caused by a
      dermatophyte, which is most commonly of the Trichophyton genus and less commonly
      of the Microsporum or Epidermophyton genera. Tinea capitis, tinea pedis, and
      onychomycosis are common dermatologic diseases that may result from such an
      infection. The treatment of fungal infections caused by a dermatophyte has been
      successful when treated with oral or topical antifungal agents. Terbinafine,
      itraconazole, and fluconazole are oral antimycotics that are effective in the
      treatment of superficial mycoses, although, depending on the severity of the
      infection, a topical antifungal may be sufficient.

PMID- 16282754
TI  - Targeting the "target lesions".

PMID- 16282756
TI  - Why a historical approach has clinical benefits: Staphylococcus toxoid and
      autohemotherapy.

PMID- 16282755
TI  - The centenary of treponema pallidum: on the discovery of Spirochaeta pallida.

PMID- 16282757
TI  - Never perform patch tests in a patient on antihistamines--dispelling the myth.

PMID- 16282758
TI  - MetroGel (metronidazole) topical gel, 1%.

PMID- 16282759
TI  - Chronic granulomatous disease: two members of a single family with different
      dermatologic manifestations.
AB  - Case 1: A 33-year-old man with a 14-year history of localized skin disease on the
      face and scalp was evaluated at the department of dermatology. The physical
      examination revealed plaques with papules, pustules, and a golden yellow crusting
      on the forehead, cheeks, upper lip, and chin (Figure 1). The scalp presented
      fine, whitish scales. At the beginning of his disease, the patient presented
      large red and painful purulent boils. The 14-year clinical course of these
      lesions was characterized by partial remissions and recurrences, but he did not
      specify any treatment related to improvement. The clinical diagnosis given for
      the scalp lesions was seborrheic dermatitis. For the facial lesions, many
      differential diagnoses were considered, among them: seborrheic dermatitis,
      acneiform dermatitis, impetigo, folliculitis, seborrheic pemphigus, and
      demodicidosis. The histopathologic study of a biopsy taken from the cheek (Figure
      2) showed superficial spongiform dermatitis with neutrophils and folliculitis
      that are compatible with the diagnosis of seborrheic dermatitis. Both Gram and
      periodic acid-Schiff stains were negative. Follow-up of the patient was not
      possible since he did not come back. The disease in this patient initially
      manifested at age five by the presence of recurrent ganglionic abscesses. At age
      15, he presented a pulmonary abscess of a left lobule that was surgically
      removed; at this point the diagnosis of chronic granulomatous disease was
      established. At age 28, an exploratory laparotomy was performed due to
      peritonitis and multiple hepatic abscesses. At that time, he was treated with
      antibiotics (mainly trimethoprim-sulfamethoxazole) and interferon-g. The patient
      had two brothers who died due to complications of chronic granulomatous disease.
      In addition, both his mother and sister presented a history of discoid lupus-like
      lesions. Case 2: Coincidentally, his 27-year-old sister was seen in our
      department of dermatology 5 years before, presenting infiltrated and erythematous
      plaques with fine scales (Figure 3) on the right side of the nose and the left
      annular finger. No other cutaneous or mucous lesions were seen. She referred
      onset in childhood with similar lesions on sun-exposed areas that disappeared
      without scarring. A biopsy was performed and the results were compatible with the
      diagnosis of discoid lupus erythematosus (Figure 4). Direct immunofluorescence
      was not available. At that time, she did not mention the family history of
      chronic granulomatous disease. Clinical follow-up was not possible, but his
      brother referred that she afforded complete remission only with sun protection.

PMID- 16282760
TI  - Skin dimpling as a delayed manifestation of traumatic amniocentesis.
AB  - A 2-month-old infant girl was seen for marks on her abdomen. Born after a 39
      week, 2-day normal twin gestation to a 37-year-old healthy multiparous mother,
      the prepartum history for "Baby B" was significant only for amniocentesis at 17
      weeks' gestation, where three needle insertions were required for obtaining
      amniotic fluid from "Baby B." During amniocentesis, performed under ultrasound
      guidance by an experienced obstetrician, the amniocentesis needle was misplaced
      in the fetal abdomen in one of the failed attempts. No evident adverse sequelae
      were noted and the pregnancy proceeded without complication. As the baby gained
      weight, by 6 weeks of life two indentations appeared on the skin, becoming more
      pronounced as the baby became chubbier. Aside from this finding, the baby was
      otherwise healthy. Close examination revealed nontender skin-colored focal
      puckering on the right anterior lower abdomen and the right flank. No induration,
      fluid exudation, or fistulous opening was evident. At 13 months of age, the
      lesions remained stable and asymptomatic.

PMID- 16282761
TI  - Current trends in the diagnosis and management of head and neck paragangliomas.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the
      diagnosis and management of head and neck paragangliomas. RECENT FINDINGS: The
      review will focus on three main areas of interest: genetics, newer imaging
      modalities, and management with radiation therapy. SUMMARY: The succinate
      dehydrogenase enzyme complex is important in the pathogenesis of paragangliomas.
      Magnetic resonance angiography and functional imaging have become very helpful in
      diagnosing these tumors. Surgery is still the mainstay of therapy, but
      conventional or stereotactic radiotherapy seems to be a very safe option in very
      large or inoperable tumors.

PMID- 16282762
TI  - Mechanisms of hair cell death and protection.
AB  - PURPOSE OF REVIEW: Sensory hair cells are mechanotransducers of the inner ear
      that are essential for hearing and balance. Hair cell death commonly occurs
      following acoustic trauma or exposure to ototoxins, such as the aminoglycoside
      antibiotics and the antineoplastic agent cisplatin. Loss of these inner ear
      sensory cells can lead to permanent sensorineural hearing loss, balance
      disturbance, or both. Currently, the only effective clinical intervention is
      prevention from exposure to known ototoxic insults. To help improve therapeutic
      strategies, a better understanding of the molecular mechanisms underlying hair
      cell degeneration is required. Current knowledge of these cell death mechanisms
      and potential therapeutic targets are discussed in this review. RECENT FINDINGS:
      Studies have shown that caspase-9 and caspase-3 are key mediators of hair cell
      death induced by noise, aminoglycosides, and cisplatin. The Bcl-2 family consists
      of a group of proapoptotic and antiapoptotic molecules that act upstream of and
      regulate caspase activation. Recent studies have shed light on the roles of
      molecules acting more upstream, including mitogen-activated protein kinases and
      p53. SUMMARY: The mechanisms of sensory hair cell degeneration in response to
      different ototoxic stimuli share a final common pathway: caspase activation.
      Inhibition of caspases prevents or delays hair cell death and may preserve
      hearing/balance function. Inhibition of mitogen-activated protein kinases
      protects against noise-induced and aminoglycoside-induced but not cisplatin
      induced hair cell death, which suggests divergent upstream regulatory mechanisms.

PMID- 16282763
TI  - Cosmetic and reconstructive medical tattooing.
AB  - PURPOSE OF REVIEW: Cosmetic and reconstructive medical tattooing techniques are
      being used with a higher frequency than ever before. The volume of scientific
      research into its basics, however, is too small to prevent the present occurrence
      of complications. This review shows that most of the recent articles on the
      subject are in fact case reports and that many of the complications described
      result from the failure to conduct more research. RECENT FINDINGS: Recent
      findings include few and relatively unimportant new techniques, studies
      describing tattoo removal with laser, magnetic displacement and chemical
      irritants, more findings about infections and allergies, and complications with
      high field-strength magnetic resonance imaging scans. SUMMARY: Recent literature
      contains very few useful studies because generally they are not supported by
      sufficient scientific research.

PMID- 16282764
TI  - Recurrent respiratory papillomatosis: pathogenesis to treatment.
AB  - PURPOSE OF REVIEW: Recurrent respiratory papillomatosis remains a serious disease
      and is commonly treated by otolaryngologists. The goals of this review are to
      update physicians on current understandings regarding viral pathogenesis, patient
      risks, and current trends in treatment strategies. RECENT FINDINGS: Surgical
      debulking still remains the foundation of treatment; however, newer surgical
      approaches utilizing microdebriders are replacing laser ablation. Genetic studies
      have identified individuals with specific immune cell alleles to be at greater
      risk for persistent infection. Our understanding of the viral pathogenesis has
      increased by the identification of a viral mechanism to downregulate antigen
      expression in cells infected with human papillomavirus, thus possibly allowing
      decreased immune detection. Although the viral types responsible for recurrent
      respiratory papillomatosis have been identified, the mechanism by which they
      alter cellular growth has not been identified. Research studies investigating
      adjuvant medical therapies aimed at reducing required surgical therapy intervals
      and possibly helping cure the infection are being completed. A safe, effective
      adjuvant therapy is still currently not available. SUMMARY: Improved surgical
      approaches have slightly enhanced patient care; however, more research is needed
      to understand how human papillomavirus causes disease so that these therapies can
      be developed.

PMID- 16282765
TI  - Pediatric obstructive sleep apnea: the year in review.
AB  - PURPOSE OF REVIEW: In recent years several daytime symptoms resulting from
      pediatric obstructive sleep apnea have been recognized that affect
      neurobehavioral and cognitive functioning. It is important to identify patients
      who will benefit from treatment. Up until now the systematic analysis of
      obstructive sleep apnea in children has been hindered by both variable diagnostic
      criteria and patient care protocols. This review examines the effects of
      obstructive sleep apnea in children as well as treatment outcomes. Recent data
      suggest that some diagnostic modalities may underestimate the prevalence of sleep
      disordered breathing in children. RECENT FINDINGS: A review of the data from the
      past year shows a significant correlation between obstructive sleep apnea and
      daytime symptoms. It also shows mitigation of these symptoms with appropriate
      treatment. The directed history and physical examination continue to be the most
      effective means of diagnosis in most affected children. The polysomnogram is
      considered the gold standard for diagnosis but may underestimate the presence of
      sleep-disordered breathing in children. Some children with the diagnosis of
      primary snoring will benefit from treatment. SUMMARY: In view of the profound
      effects of obstructive sleep apnea in children, it is vital to develop an
      accurate and universal system for diagnosing and treating these patients.
      Adenotonsillar hypertrophy is the major cause of obstructive sleep apnea in
      children. A directed history and physical examination followed by tonsillectomy
      and adenoidectomy are effective in improving the physical sequelae and quality of
      life of affected children.

PMID- 16282766
TI  - Velopharyngeal dysfunction: evolving developments in evaluation.
AB  - PURPOSE OF REVIEW: Otolaryngologists are increasingly being called upon to assist
      in the differential diagnosis of velopharyngeal valving disorders for speech,
      assisting in treatment planning and the assessment of treatment outcomes. RECENT
      FINDINGS: The most commonly used methods for direct visualization of
      velopharyngeal function remain nasendoscopy and videofluoroscopy. Literature
      supporting the use of either nasendoscopy followed by videofluoroscopy or the
      reverse can be found. Several studies also suggest that magnetic resonance
      imaging can make important contributions to the evaluation of velopharyngeal
      anatomy and function. The routine use of magnetic resonance imaging for
      evaluating the velopharynx is neither practical nor probable at the present time.
      Although magnetic resonance imaging may be as effective as videofluoroscopy or
      nasendoscopy, the cost of magnetic resonance imaging and the radiation exposure
      of videofluoroscopy will likely dictate that nasendoscopy continues to be the
      most common technique for evaluating velopharyngeal function during speech.
      Several recent studies have documented the use of instrumental assessment of
      velopharyngeal function for assigning patients to a given surgical procedure,
      predicting surgical success or complications, and evaluating treatment outcomes.
      SUMMARY: There are still discussions and conflicting results regarding the best
      method for evaluating velopharyngeal function. Opinions conflict regarding the
      various methods, which suggests that no single method is best. The decision
      regarding the most appropriate evaluation protocol should be guided by the
      information that the clinician is attempting to obtain and the relative benefits
      and risks of each method. Increasingly, these evaluation methods are used by the
      otolaryngologist to assist in the differential diagnosis of velopharyngeal
      valving disorders, the assignment of patients to various treatment options, and
      the evaluation of treatment outcomes.

PMID- 16282767
TI  - Velo-cardio-facial syndrome: the pediatric otolaryngologist's perspective.
AB  - PURPOSE OF REVIEW: The understanding of velo-cardio-facial syndrome has grown
      markedly since the initial descriptions of this common genetic disorder nearly 30
      years ago. Our knowledge of the syndrome has advanced in part from opportunities
      to monitor many patients into adulthood because of advances in the fields of
      cardiothoracic surgery and immunology. Longitudinal study has brought to light
      psychiatric and behavioral features of the syndrome that are often not apparent
      until late adolescence or the early adult years. Certain endocrine and
      immunologic features of the syndrome thought to be resolved in childhood are now
      witnessed in older patients. Variable expression and lack of disease awareness
      are two major factors that contribute to the delays in diagnosis in many cases.
      To address this, there has been a call to delineate screening parameters for
      patients at risk of carrying the deletion. RECENT FINDINGS: Several areas are
      highlighted in this review, reflecting the focus of scholarly work on velo-cardio
      facial syndrome in the past year. Molecular genetics has shown smaller deletions
      in many families with the syndrome. The gene TBX1 has been found to be important
      to the phenotype. Surgical outcomes data reveal the greater challenges involved
      in correcting velopharyngeal insufficiency. SUMMARY: Defining the genetic basis
      of velo-cardio-facial syndrome will allow clinicians and basic scientists to make
      further inroads into understanding the variable expressivity of this syndrome. It
      is also important to be aware of the continued diagnostic challenges encountered
      by clinicians in attempts to improve the detection of patients with this
      syndrome.

PMID- 16282768
TI  - Bibliography. Current world literature. Pediatric otolaryngology.

PMID- 16282771
TI  - Hereditary angioedema.
AB  - PURPOSE OF REVIEW: Major advances have been made in understanding the clinical
      signs and symptoms, the pathophysiology and the treatment of hereditary
      angioedema. This disease that often begins in childhood is caused by partial
      absence of the plasma protein C1-inhibitor. At the present time five
      pharmaceutical companies are planning or conducting clinical trials of a variety
      of agents to treat acute attacks of this illness. Here we review our current
      understanding of this illness and the current approaches to treatment. RECENT
      FINDINGS: This disease is often missed in childhood or confused with other
      illness. The clinical signs and symptoms are reviewed. The importance of the
      kinin generating pathway and bradykinin in causing edema has become central to
      our understanding of pathophysiology. The many new approaches to therapy all
      appear promising. SUMMARY: Currently we have effective chronic therapy for this
      disease, although available drugs have real or potential difficulties in use in
      children. In the future it is likely that effective therapy for acute attacks of
      disease will become available in the US. It is important to recognize the
      clinical manifestations of this potentially fatal illness and to understand the
      therapeutic options.

PMID- 16282772
TI  - Eosinophilic esophagitis.
AB  - PURPOSE OF REVIEW: Previously perceived as an anomaly, eosinophilic esophagitis
      is now frequently diagnosed by both pediatric and adult specialists including
      gastroenterologists, allergists, pathologists, and otolaryngologists. Research
      efforts initially focused on characterization of the clinical, endoscopic, and
      histologic features of this disorder. In the last 3 years, the research focus has
      evolved into understanding its immunologic and demographic features as well as
      the development of efficacious therapies. RECENT FINDINGS: Population-based
      demographic studies have documented the unique epidemiologic parameters of
      eosinophilic esophagitis, some of its natural history, and its increasing
      frequency. Basic research efforts have identified cytokines relevant toward
      development of eosinophilic esophagitis, including interleukin-5 and interleukin
      13. Clinical efforts have established the efficacy of dietary and medical
      treatments. Some treatments result in symptomatic improvement with ongoing
      inflammation, so a debate is ensuing over the long-term effect of asymptomatic
      esophageal inflammation. SUMMARY: Understanding of eosinophilic esophagitis has
      evolved to a point at which patients can be appropriately diagnosed and initially
      treated; however, a paucity of long-term outcome data prevents the creation of
      uniform recommendations for the clinical care of patients with eosinophilic
      esophagitis.

PMID- 16282773
TI  - Update on pediatric vasculitis.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the
      recent research and progress made in the field of pediatric vasculitis. RECENT
      FINDINGS: Over the past year, researchers have described several polymorphisms in
      Henoch-Schonlein purpura and Kawasaki Disease as well as the association between
      various vasculitides and infections. International and multidisciplinary efforts
      in Kawasaki Disease have resulted in recommendations for its diagnosis,
      treatment, and long-term management to improve patient care and further increase
      global collaboration. Researchers are investigating the role of inflammation and
      its role in endothelial health and atherosclerosis. Treatment regimens continue
      to improve, with the use of different immunosuppressive medications; however, we
      continue to have incomplete treatment successes. SUMMARY: Vasculitides are rare
      conditions with significant morbidity and mortality whose prognosis has improved
      with newer diagnostic modalities and treatments; however, we continue to have
      insufficient knowledge of vasculitides and lack unambiguous diagnostic criteria.
      As technology continues to progress it is clear that a single cause of these
      diseases may be an oversimplification: the genetic makeup of individuals, as well
      as various environmental exposures, are of vital importance in the
      pathophysiology and evolution of disease processes, as well as response to
      therapy. Efforts should continue to improve international multicenter
      collaboration and interdisciplinary efforts to help solve this ever-growing
      puzzle.

PMID- 16282774
TI  - Bone health in pediatric rheumatic disease.
AB  - PURPOSE OF REVIEW: Children with chronic rheumatic disease have decreased bone
      mass. In adults, lowered bone mineral density is associated with increased
      fracture risk. This morbidity is undetermined in pediatric rheumatic disease as
      osteoporosis has not been well-defined in children. This review compares methods
      for determining bone mass in children, examines insights into molecular
      mechanisms of bone metabolism, and discusses the prevention and treatment of
      decreased bone mass in children. RECENT FINDINGS: Peak bone mass, attained during
      adolescence and early adulthood, is critical in determining fracture risk.
      Studies of children with chronic rheumatic disease demonstrate decreased bone
      mineral density, and potentially lowered peak bone mass. Dual energy x-ray
      absorptiometry is the most commonly used technique for monitoring bone mineral
      density and should be interpreted utilizing age-appropriate Z-scores. Recent
      studies suggest quantitative ultrasound may be as reliable as dual energy x-ray
      absorptiometry and lacks radiation exposure. The molecular mechanisms by which
      inflammation alters bone mineral density involve receptor activator of nuclear
      factor kappaB ligand (RANKL)/osteoprotegerin, tumor necrosis factor-alpha, and
      interleukin-1. Limited data on the use of bisphosphonates and calcitonin in
      children suggest they are safe and effective, but should be used cautiously.
      SUMMARY: Children with chronic rheumatic disease should have bone mass monitored
      by dual energy x-ray absorptiometry Z-scores. Targeting the RANKL/osteoprotegerin
      pathway may lead to therapies that improve bone health in this population. More
      studies on the role of bisphosphonates and calcitonin must be pursued to
      establish guidelines for use in pediatric patients with chronic rheumatic
      disease. For now, supplemental calcium and vitamin D should be implemented in
      these children.

PMID- 16282775
TI  - The use of genetic testing in the evaluation of hearing impairment in a child.
AB  - PURPOSE OF REVIEW: To review the role of genetic testing in the evaluation of
      hearing impairment in children. RECENT FINDINGS: The introduction of genetic
      testing has greatly enhanced the evaluation of deafness and hearing impairment in
      children. It can save time and money as well as providing patients, their
      families, and their physicians with important information; however, this testing
      is different from the medical testing that pediatricians typically order.
      SUMMARY: For patients and families to realize the benefits of genetic testing it
      must be done early in the evaluation process and must be accompanied by
      appropriate pretest and posttest counseling.

PMID- 16282776
TI  - First trimester ultrasound screening for fetal aneuploidy and middle cerebral
      artery Doppler assessment for fetal alloimmunization.
AB  - PURPOSE OF REVIEW: Traditional methods of fetal evaluation require invasive
      procedures (e.g. amniocentesis) with an inherent, albeit low, risk of
      complications and pregnancy loss. As medical knowledge and ultrasound technology
      have advanced, noninvasive modes of fetal evaluation have become increasingly
      used. Two disorders in which this has been most applied are fetal aneuploidy and
      alloimmunization to red blood cell antigens. RECENT FINDINGS: First-trimester
      screening protocols for fetal aneuploidy combine ultrasound measurement of the
      fetal nuchal translucency with the measurement of two maternal serum hormones,
      free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A.
      This combination detects approximately 85% of women pregnant with fetuses with
      trisomy 21. An increase in the velocity of fetal middle cerebral artery blood
      flow occurs in the setting of moderate to severe fetal anemia and can be measured
      with Doppler ultrasound. Middle cerebral artery evaluation is equally sensitive
      in the prediction of anemia as amniocentesis for bilirubin breakdown products and
      has less associated risk. It has an additional benefit because it can also be
      applied to causes of anemia other than hemolysis. SUMMARY: Noninvasive methods of
      fetal assessment are becoming increasingly commonplace. There has been a dramatic
      decrease in the use of prenatal diagnostic services as screening strategies have
      become available. Doppler assessment of the velocity of blood flow through the
      fetal middle cerebral artery will allow for more judicious application of
      invasive procedures to pregnancies at significant risk for anemia.

PMID- 16282777
TI  - Advances in X-linked mental retardation.
AB  - PURPOSE OF REVIEW: Mutations in genes on the X chromosome rival chromosome
      aberrations as a cause of mental retardation. Progress in the clinical and
      molecular delineation of X-linked mental retardation has outpaced progress in
      understanding autosomal mental retardation. This is a result in large part of the
      identification of large families in which mental retardation has segregated in an
      X-linked pattern and the greater ease with which molecular technologies can be
      applied to hemizygosity in males. RECENT FINDINGS: About one-third of the
      estimated 165 genes associated with syndromal mutations of genes on the X
      chromosome and one-fourth of the estimated 100 genes associated with nonsyndromal
      mutations of genes on the X chromosome have been identified. In a number of
      instances, the same gene is responsible for syndromal and nonsyndromal mutations
      of genes on the X chromosome. The molecular delineation of mutations of genes on
      the X chromosome has allowed certain conditions to be lumped together on the
      basis of allelism and has caused others that appear clinical similar to remain
      separate. SUMMARY: The clinical and molecular advances have allowed X-linked
      mental retardation to be more clearly delineated, have provided the means of
      confirmatory laboratory testing, and have ushered in an era of carrier testing,
      prenatal diagnosis, and prevention strategies.

PMID- 16282778
TI  - Velo-cardio-facial syndrome.
AB  - PURPOSE OF REVIEW: Velo-cardio-facial syndrome has emerged from obscurity to
      become one of the most researched disorders this past decade. It is one of the
      most common genetic syndromes in humans, the most common contiguous gene syndrome
      in humans, the most common syndrome of cleft palate, and the most common syndrome
      of conotruncal heart malformations. Velo-cardio-facial syndrome has an expansive
      phenotype, a factor reflected in the wide range of studies that cover both
      clinical features and molecular genetics. In this review, we cover multiple areas
      of research during the past year, including psychiatric disorders, neuroimaging,
      and the delineation of clinical features. RECENT FINDINGS: The identification of
      candidate genes for heart anomalies, mental illness, and other clinical
      phenotypes has been reported in the past year with a focus on TBX1 for cardiac
      and craniofacial phenotypes and COMT and PRODH for psychiatric disorders. The
      expansive phenotype of velo-cardio-facial syndrome continues to grow with new
      behavioral and structural anomalies reported. Treatment issues are beginning to
      draw attention, although most authors continue to focus on diagnostic issues.
      SUMMARY: Its high population prevalence, estimated to be as common as 1:2000 has
      sparked a large amount of research, as has the model the syndrome serves for
      identifying the causes of mental illness and learning disabilities, but it is
      obvious that more information is needed. Intensive scrutiny of velo-cardio-facial
      syndrome will undoubtedly continue for many years to come with the hope that
      researchers will turn more of their attention to treatment and treatment
      outcomes.

PMID- 16282780
TI  - Advances in overgrowth syndromes: clinical classification to molecular
      delineation in Sotos syndrome and Beckwith-Wiedemann syndrome.
AB  - PURPOSE OF REVIEW: The clinical importance of overgrowth syndromes in the
      pediatric patient population has been increasingly recognized during the past
      decade, but clinical overlap among overgrowth syndromes often makes diagnostic
      categorization difficult. Advances in the molecular delineation of overgrowth
      syndromes in recent years have furthered our knowledge of the phenotypic spectrum
      of this group of conditions. This review focuses on developments in our
      understanding of the molecular mechanisms and phenotype-genotype correlations in
      the two most common overgrowth syndromes, Beckwith-Wiedemann syndrome and Sotos
      syndrome. The implications of these findings with respect to clinical diagnosis,
      medical management, and genetic counseling are discussed. RECENT FINDINGS: Recent
      reports have redefined the cardinal clinical features of Sotos syndrome, and the
      identification of two distinct types of molecular alterations in patients with
      this syndrome has enabled assessment of phenotype-genotype correlations. Recent
      studies in patients with Beckwith-Wiedemann syndrome have further expanded our
      understanding of the causative molecular mechanisms of this condition and provide
      evidence for specific genotype-phenotype correlations, most notably with respect
      to tumor risk. SUMMARY: Recognition of childhood overgrowth and investigation of
      diagnostic causes is important in anticipating appropriate medical management and
      facilitating the provision of genetic counseling. New developments in our
      understanding of the molecular basis and phenotypic expression of overgrowth
      syndromes provide additional tools in this often challenging process.

PMID- 16282779
TI  - Progress toward discerning the genetics of cleft lip.
AB  - PURPOSE OF REVIEW: Orofacial clefts are common birth defects with a known genetic
      component to their etiology. Most orofacial clefts are nonsyndromic, isolated
      defects, which can be separated into two different phenotypes: (1) cleft lip with
      or without cleft palate and (2) cleft palate only. Both are genetically complex
      traits, which has limited the ability to identify disease loci or genes. The
      purpose of this review is to summarize recent progress of human genetic studies
      in identifying causal genes for isolated or nonsyndromic cleft lip with or
      without cleft palate. RECENT FINDINGS: The results of multiple genome scans and a
      subsequent meta-analysis have significantly advanced our knowledge by revealing
      novel loci. Furthermore, candidate gene approaches have identified important
      roles for IRF6 and MSX1. To date, causal mutations with a known functional effect
      have not yet been described. SUMMARY: With the implementation of genome-wide
      association studies and inexpensive sequencing, future studies will identify
      disease genes and characterize both gene-environment and gene-gene interactions
      to provide knowledge for risk counseling and the development of preventive
      therapies.

PMID- 16282781
TI  - Genetics training in the genomic era.
AB  - PURPOSE OF REVIEW: Although major advances have been made in understanding the
      genetic basis of both rare and common disorders, the number of trainees entering
      medical genetics in recent years has been dwindling. This review summarizes some
      possible reasons for this decline and suggests approaches to increase the number
      of people who enter the field. RECENT FINDINGS: In October 2004 a 'summit
      meeting' was held at the Banbury Conference Center to discuss the problem. The
      meeting was attended by leaders in medical genetics from the United States and
      Canada. Several suggestions were made at the meeting that have resulted in new
      initiatives to alter medical genetics training and recruit additional trainees.
      SUMMARY: Major initiatives are being launched that will position medical genetics
      to work in collaboration with other specialties to lead the integration of
      genetics into medical practice.

PMID- 16282782
TI  - Healthcare insurance for all children: a necessary first step towards improving
      the health of the nation.

PMID- 16282783
TI  - Being uninsured: impact on children's healthcare and health.
AB  - PURPOSE OF REVIEW: There are 8.4 million uninsured children in the United States.
      Many are eligible for coverage. Current literature on how lack of health
      insurance affects the quality and outcome of children's healthcare in the United
      States is reviewed, and effective solutions are identified. Recent policy changes
      have produced restrictions on basic preventive and curative services, despite
      concurrent major efforts to increase insurance coverage rates for children.
      RECENT FINDINGS: With more than 70% of currently uninsured children eligible for
      either Medicaid or the State Children's Health Insurance Program, these public
      programs have not yet produced expected levels of coverage. Health systems and
      provider accountability for the primary care of uninsured children is not
      optimal. Families of uninsured children face non-financial access barriers to
      care such as lack of continuity with a primary care provider and inadequate visit
      time. These barriers are compounded for uninsured children with special
      healthcare needs. SUMMARY: Pediatric primary care effectiveness is significantly
      reduced by insurance shortfalls. Lack of coverage inhibits appropriate care
      seeking; diminishes provider availability; compromises care content, quality, and
      satisfaction; and ultimately harms the entire family unit. However, provision of
      insurance alone is not a panacea.

PMID- 16282784
TI  - The impact of Medicaid on children's healthcare and health.
AB  - PURPOSE OF REVIEW: This article reviews the impact of the Medicaid program,
      including the proportion of children in America insured by Medicaid; the extent
      to which Medicaid-enrolled children have access to care; the use of services and
      the quality of care received by Medicaid enrollees, including evidence for
      disease reduction; and family satisfaction with the program. RECENT FINDINGS:
      More than a quarter of all children in the United States were insured through
      public programs, primarily Medicaid, in 2002. Public insurance programs are even
      more critical for low-income children: 69.5% of children in families with incomes
      below 100% of the federal poverty level are covered by public programs. The reach
      of Medicaid is extensive, although substantial numbers of eligible children
      remain uninsured. Although Medicaid-insured children still face access barriers,
      particularly for certain types of specialty care, parents of children with public
      insurance report high levels of satisfaction with their experience with well
      child care. While the study findings are mixed, several recent studies show very
      favorable comparisons between the experience of privately insured children and
      that of publicly insured children. SUMMARY: Medicaid plays a critical role in
      providing health insurance coverage for children, particularly for very low
      income families. Additional efforts are needed to fully enroll all eligible
      families and to assure full access to high-quality care.

PMID- 16282785
TI  - The State Children's Health Insurance Program.
AB  - PURPOSE OF REVIEW: The State Children's Health Insurance Program expanded public
      health insurance to children who are ineligible for Medicaid yet unable to afford
      private health insurance. The program was a natural experiment, offering the
      opportunity to study the effects of expanding health insurance to a large
      population of children who would otherwise be uninsured. The State Children's
      Health Insurance Program is reviewed in the context of program goals, evaluation
      dimensions, past and current findings, and future directions. The studies and
      findings fall into five dimensions: (1) outreach/enrollment/uptake and profile of
      enrollees, (2) impact on insurance coverage and uninsured rates, (3) coverage
      dynamics, (4) impact on outcomes, and (5) costs. RECENT FINDINGS: Older studies
      focused on outreach, enrollment, characteristics of enrollees, disenrollment, and
      coverage dynamics. Current studies report the impact of the program on outcomes-
      including access to care, quality, satisfaction, unmet need, and health outcomes-
      for the overall population of children and for vulnerable subgroups, including
      racial and ethnic minorities and children with chronic illness. A smaller number
      of studies address costs. SUMMARY: The State Children's Health Insurance Program
      is evolving with demonstrated successes and areas for improvement. This
      information can enhance practicing pediatricians' understanding of barriers that
      face low-income children and families in seeking care for their children, can
      offer insight into what health insurance can and cannot do in terms of
      ameliorating those barriers, can provide insight into the prior experiences and
      current medical needs that a new enrollee in the program might have at the first
      visit to a practitioner, and can illuminate the challenges that low-income
      children and families may face in obtaining and maintaining health insurance
      coverage.

PMID- 16282786
TI  - Sleep disorders, immunizations, sports injuries, autism.
AB  - PURPOSE OF REVIEW: The purpose of this article is to summarize and synthesize the
      recent literature in four very important areas for pediatric office practice:
      sleep disorders, new immunizations, sports injuries, and autism. Important
      articles in each area are highlighted. RECENT FINDINGS: The management of
      pediatric and adolescent sleep disorders is in the forefront of the pediatric
      literature. The most recent literature cautions practitioners on prescribing
      pharmacologic treatment for sleep problems in children and adolescents. Several
      new immunizations targeted for adolescents are on the horizon. The newest
      recommendations for their delivery are outlined here. Recent sports injury
      literature emphasizes the need of the practitioner to address sports injury
      prevention and to provide anticipatory guidance at pediatric office visits.
      Finally, the past year's literature demonstrates that there is significant
      interest in autism spectrum disorders, but the clinicians' challenge for making
      the correct diagnosis of these disorders remains. SUMMARY: The literature
      presented and summarized here will give the practicing pediatrician practical
      working knowledge of four important office-based pediatric topics: sleep
      disorders, new immunizations, sports injuries, and autism.

PMID- 16282787
TI  - Bibliography. Current world literature. Allergy, immunology and related
      disorders.

PMID- 16282788
TI  - 2005 Founders Award.

PMID- 16282789
TI  - 2005 Elda E. Anderson Award.

PMID- 16282790
TI  - 2005 Distinguished Scientific Achievement Award.

PMID- 16282791
TI  - 2005 Outstanding Science Teacher Award.

PMID- 16282792
TI  - 2005 Robley D. Evans Commemorative Medal.

PMID- 16282794
TI  - 2005 William A. McAdams Outstanding Service Award.

PMID- 16282795
TI  - A case study of the estimation of occupational internal dose using urinary
      excretion data obtained in a biomedical research facility.
AB  - This paper presents a fundamental investigation of the screening of intakes and
      the estimation of internal doses for workers at a biomedical research facility
      from their urinary excretion data. Urine samples from the workers were collected
      immediately before and several days after handling radioactive materials, and 5
      mL portions were measured directly with a sodium iodide scintillation detector or
      a liquid scintillation detector. Intakes of radionuclides and effective doses
      were estimated from the data using the Internal Dose Easy Calculation code. Blank
      levels of radioactivity and detection limits for this method were determined from
      the radioactivity contained in urine samples collected from volunteers working
      outside the controlled area (control samples). Most of the radioactivity in the
      control samples was attributed to K. Under the present experimental conditions,
      the detection limits for the committed effective doses were 7.5 x 10(-4) mSv for
      125I and 6.9 x 10(-2) mSv for 35S in the case of samples collected 1 d after
      handling. Accordingly, it can be determined whether workers were exposed more
      than the recording level (1 mSv of committed effective dose) or not. No workers
      in the surveyed facility were found to suffer internal exposure beyond the
      recording levels, and their intakes were estimated to be below the detection
      limits in the 2-y investigation period. In an ordinary facility of biomedical
      research, the amount of unsealed radioactivity handled at one time is within 10
      MBq in many cases, and the air ventilation and filtering systems work adequately.
      Under such circumstances, the present results suggest that individual monitoring,
      such as urine analysis, is omissible in many cases as a routine monitoring of
      internal exposure for workers.

PMID- 16282797
TI  - Photon dose conversion coefficients for human teeth in standard irradiation
      geometries.
AB  - Photon dose conversion coefficients for human tooth materials are computed in
      energy range from 0.01 to 10 MeV by the Monte Carlo method. The voxel phantom
      "Golem" of the human body with newly defined tooth region and a modified version
      of the EGS4 code have been used to compute the coefficients for 30 tooth cells
      with different locations and materials. The dose responses are calculated for
      cells representing buccal and lingual enamel layers. The computed coefficients
      demonstrate a strong dependence on energy and geometry of the radiation source
      and a weaker dependence on location of the enamel voxels. For isotropic and
      rotational radiation fields, the enamel dose does not show a significant
      dependence on tooth sample locations. The computed coefficients are used to
      convert from absorbed dose in teeth to organ dose or to integral air kerma.
      Examples of integral conversion factors from enamel dose to air kerma are given
      for several photon fluences specific for the Mayak reprocessing plant in Russia.
      The integral conversion factors are strongly affected by the energy and angular
      distributions of photon fluence, which are important characteristics of an
      exposure scenario for reconstruction of individual occupational doses.

PMID- 16282796
TI  - The "AQUASCOPE" simplified model for predicting 89,90Sr, 131I, and 134,137Cs in
      surface waters after a large-scale radioactive fallout.
AB  - Simplified dynamic models have been developed for predicting the concentrations
      of radiocesium, radiostrontium, and I in surface waters and freshwater fish
      following a large-scale radioactive fallout. The models are intended to give
      averaged estimates for radionuclides in water bodies and in fish for all times
      after a radioactive fallout event. The models are parameterized using empirical
      data collected for many lakes and rivers in Belarus, Russia, Ukraine, UK,
      Finland, Italy, The Netherlands, and Germany. These measurements span a long time
      period after fallout from atmospheric nuclear weapons testing and following the
      Chernobyl accident. The models thus developed were tested against independent
      measurements from the Kiev Reservoir and Chernobyl Cooling Pond (Ukraine) and the
      Sozh River (Belarus) after the Chernobyl accident, from Lake Uruskul (Russia),
      following the Kyshtym accident in 1957, and from Haweswater Reservoir (UK),
      following atmospheric nuclear weapons testing. The AQUASCOPE models (implemented
      in EXCEL spreadsheets) and model documentation are available free of charge from
      the corresponding author.

PMID- 16282798
TI  - Determination of gross alpha, 224Ra, 226Ra, and 228Ra activities in drinking
      water using a single sample preparation procedure.
AB  - The current federal and New Jersey State regulations have greatly increased the
      number of gross alpha and radium tests for public and private drinking water
      supplies. The determination of radium isotopes in water generally involves
      lengthy and complicated processes. In this study, a new approach is presented for
      the determination of gross alpha, 224Ra, 226Ra, and 228Ra activities in water
      samples. The method includes a single sample preparation procedure followed by
      alpha counting and gamma-ray spectroscopy. The sample preparation technique
      incorporates an EPA-approved co-precipitation methodology for gross alpha
      determination with a few alterations and improvements. Using 3-L aliquots of
      sample, spiked with 133Ba tracer, the alpha-emitting radionuclides are isolated
      by a BaSO4 and Fe(OH)3 co-precipitation scheme. First the gross alpha-particle
      activity of the sample is measured with a low-background gas-flow proportional
      counter, followed by radium isotopes assay by gamma-ray spectroscopy, using the
      same prepared sample. Gamma-ray determination of 133Ba tracer is used to assess
      the radium chemical recovery. The 224Ra, 226Ra, and 228Ra activities in the
      sample are measured through their gamma-ray-emitting decay products, 212Pb,
      214Pb/214Bi, and 228Ac, respectively. In cases where 224Ra determination is
      required, the gamma-ray counting should be performed within 2-4 d from sample
      collection. To measure 226Ra activity in the sample, the gamma-ray spectroscopy
      can be repeated 21 d after sample preparation to ensure that 226Ra and its
      progeny have reached the equilibrium state. At this point, the 228Ac
      equilibration with parent 228Ra is already established. Analysis of aliquots of
      de-ionized water spiked with NIST-traceable 230Th, 224Ra, 226Ra, and 228Ra
      standards demonstrated the accuracy and precision of this method. Various
      performance evaluation samples were also assayed for gross alpha as well as
      radium isotope activity determination using this procedure and the results were
      in close agreement with the assigned values. In addition, method comparison
      results of actual sample analyses agreed well with the ones performed using EPA
      approved procedures. With a 3-L sample aliquot and 1,000-min counting time, the
      average gross alpha minimum detectable concentration (MDC) was about 0.002 Bq L(
      1). The average MDC's for 224Ra, 226Ra, and 228Ra were 0.034 Bq L(-1), 0.017 Bq
      L(-1), and 0.036 Bq L(-1), respectively, based on a 3-L sample aliquot, 85%
      chemical yield, 40% intrinsic Ge detector, and 1,000-min count time. This method
      combines and simplifies the analytical procedures and reduces labor while
      achieving the precision, accuracy, and minimum detection limit requirements of
      EPA regulations.

PMID- 16282799
TI  - Occurrence of 224Ra, 226Ra, 228Ra, gross alpha, and uranium in California
      groundwater.
AB  - One hundred and twelve groundwater wells sampled from all the major aquifers in
      California were analyzed for 224Ra, 226Ra, 228Ra, gross alpha, and uranium. The
      results showed that radium is found in relatively low concentration, 1.56 x 10(
      2)-1.23 Bq L(-1) (0.42-33 pCi L(-1)) for 224Ra, 2.2 x 10(-3)-0.81 Bq L(-1) (0.06
      22 pCi L(-1)) for 226Ra, and 8.5 x 10(-3)-1.31 Bq L(-1) (0.23-35 pCi L(-1)) for
      228Ra in California groundwater. Uranium was found at the highest concentration
      on both mass and activity basis and was correlated with the gross alpha
      measurement. Short-lived radioisotopes showed no significant contribution to
      gross alpha measurements. There was a strong correlation between 224Ra and 228Ra
      activities, suggesting the latter to be an indicator for the occurrence of the
      former. Comparison of 226Ra to 238U, 224Ra to 226Ra, and 226Ra to 228Ra showed
      scattered data indicating no correlation between each of these isotope pairs.
      Approximately 4% of the wells were found to exceed the U.S. Environmental
      Protection Agency (EPA) established maximum contaminant level for total radium of
      0.185 Bq L(-1) (5 pCi L(-1)). Analysis of 228Ra by gamma-ray spectroscopy was in
      good agreement with the U.S. EPA-approved procedure.

PMID- 16282800
TI  - Uranium concentrations in South African herbal remedies.
AB  - South Africa contains some of the world's largest mineral deposits, which include
      uranium. Uranium is mined as a by-product of gold production. The uranium content
      of the surface soil and groundwater in South Africa has been measured and shows
      marked variation, depending on location. Herbal remedies are collected by
      traditional healers from many sites, some of which may be contaminated. Thirty
      herbal remedies were analyzed using a sensitive adsorptive stripping voltammetry
      method. Eight samples had levels below the limit of detection, but in five the
      levels were greatly elevated, showing concentrations above 40,000 ppb. The mean
      uranium concentration of the remainder of the specimens was of the order of
      15,000 ppb. We have attempted to put these data into context by comparison with
      other studies of absorption of uranium by the oral route.

PMID- 16282801
TI  - IEEE Committee on Man and Radiation (COMAR) Technical Information Statement
      "exposure of medical personnel to electromagnetic fields from open magnetic
      resonance imaging systems".
AB  - Open magnetic resonance imaging (MRI) systems enable performing image-guided
      medical procedures for long periods of time very close to, or inside, the patient
      imaging area. Medical personnel can be exposed to relatively high static,
      gradient, and radiofrequency fields compared to most other MRI systems. The
      Committee on Man and Radiation of the Institute of Electrical and Electronics
      Engineers calculated or used existing data on magnetic flux densities and field
      strengths in or near the patient area to assess occupational exposure levels.
      Potential exposures to each field type were analyzed and compared to relevant
      values specified in international exposure limits including those of the
      Institute of Electrical and Electronics Engineers and the International
      Commission on Nonionizing Radiation Protection. Exposures of the head or torso of
      a worker to gradient fields near the center of the patient-imaging area can
      exceed most exposure limits even for times less than a second. Exposures to
      radiofrequency fields can exceed limits if sustained exposures (minutes or more)
      occur to parts of the body. Static magnetic fields used by present Open MRI
      systems are below exposure limits of all of the standards that address these
      fields. Overall results of this study suggest that manufacturers and others who
      program or operate Open MRI systems should take care to ensure that operating
      parameters produce exposures that comply with the relevant exposure limits. Also,
      since field levels fall off rapidly with increasing distance, user practices may
      be implemented that reduce exposures significantly.

PMID- 16282803
TI  - More about misconceptions by Charles Potter.

PMID- 16282809
TI  - Effective support for certain patient populations: one agency's experience.

PMID- 16282810
TI  - A pressure ulcer case study in home health disease management.

PMID- 16282811
TI  - Conquering the dilemma of improving function.

PMID- 16282812
TI  - Compliance with the Medicare conditions of participation: keeping OASIS data
      private.

PMID- 16282813
TI  - A university-sponsored home health nursing program in Karachi, Pakistan.
AB  - This article describes a university-sponsored home health nursing program in a
      large urban center in Pakistan and details the essential elements needed in
      implementing such a program in a developing country. Compared to in-hospital
      treatment, home healthcare reduced hospital stay from 12.8 days to 3.9 days, and
      resulted in a net savings of Pakistani rupees (PRs) 5,374,135 (USD 89,569). A
      cost-effective home treatment program in a resource-limited country can be
      successfully implemented by using the hospital pharmacy as the central point for
      the preparation and distribution of medications and specialty nursing services.

PMID- 16282814
TI  - Sick-day management for the home care client with diabetes.
AB  - Clients with diabetes who experience an acute illness are at risk for severe
      hyperglycemic states or hypoglycemia that often results in emergency room visits
      or hospitalizations. Preventing these complications through educating clients in
      decision making and appropriate sick-day management is vital to positive
      outcomes. This article describes guidelines for sick-day management for home care
      clients with diabetes.

PMID- 16282816
TI  - Standards of care and best practices: the link to patient outcomes.
AB  - There is a critical link between patient outcomes achieved and the implementation
      of best practice that is often misunderstood and frequently overlooked. As OBQI
      ushers in a new outcomes-driven environment of measuring care quality, it is
      important to understand this link and implement clinical interventions
      accordingly.

PMID- 16282818
TI  - View from the Board: Position statements: official view of HPNA.

PMID- 16282819
TI  - Palliative care web sites.

PMID- 16282820
TI  - "Seeing" artificial hydration and nutrition through an ethical lens.
AB  - Nurses may be asked by conscious, rational patients to participate in the
      withdrawal of their life-sustaining nutritional support. The case study presented
      in this column gives clinicians a framework to handle these situations when they
      arise, using an ethical framework as their guide.

PMID- 16282821
TI  - Advance-directive planning: not just for patients anymore...

PMID- 16282823
TI  - Building and sustaining an adequate RN workforce.

PMID- 16282824
TI  - International nursing recruitment experience.

PMID- 16282825
TI  - Organizational turnaround: the role of the nurse executive.
AB  - For some hospitals, the complex issues associated with the current healthcare
      environment have resulted in progressive destabilization. In these situations,
      organizational turnaround is imperative to renew profitability and remain viable.
      As the administrator of the largest employee group, the nurse executive plays a
      central role in the turnaround process. The collective power and strength of the
      nursing service can move an organization by accomplishing needed changes and
      setting a tone and example for others. The author discusses the organization's
      turnaround.

PMID- 16282827
TI  - Hospitalists: a chief nursing officer's perspective.
AB  - The hospitalist "specialty" is sweeping the inpatient setting with numbers of
      physicians choosing this specialty expected to exceed 20,000 by 2010. Yet, little
      is known about the involvement of nursing in the design, implementation, and
      evaluation of a hospitalist initiative. The author suggests the chief nursing
      officer's pivotal role in proactively encouraging the design and implementation
      of a hospitalist-nurse manager patient-centered care delivery model. The chief
      nursing officer can create an environment to foster research designed to identify
      outcomes from this partnership of hospitalist and clinical (nurse) manager.

PMID- 16282826
TI  - Magnet demographic data: creating a system to streamline the process.
AB  - The benefits of Magnet status are well documented. However, the challenges of
      completing the Magnet application can overextend an organization's data
      collection processes and systems. The authors discuss the driving forces behind
      development of Step One, a cost-effective on-line system alternative to manual
      demographic data collection. The article presents an overview of staff's role in
      system development and rollout and describes improvements in efficiency,
      accuracy, and satisfaction from data collection to final American Nurse
      Credentialing Center report generation.

PMID- 16282828
TI  - Effectiveness of a clinical ladder program.
AB  - A 5-hospital system shares results of the evaluation of a clinical ladder
      program. Improvements were noted in overall satisfaction with the program, nurse
      retention of those who participated in the program, and costs savings due to
      decreased turnover. The authors point out the importance of evaluating the
      effectiveness of advancement programs for nurses. The analysis of a clinical
      ladder program in relation to costs, financial impact, and benefits helps to
      justify the salary increments for the ladder programs. This article provides the
      nurse executive with appropriate justification and outcome data to effectively
      champion these programs.

PMID- 16282829
TI  - Excellence through evidence: securing collegial/collaborative nurse-physician
      relationships, part 2.
AB  - Multiple nurse-physician (RNMD) relationships coexist on hospital units;
      collegial and collaborative (C/C) relationships positively impact patient
      outcomes more than the others. The goal of this multisite evidence-based
      management practice initiative was to identify structures that enable C/C RNMD
      relationships. In part 1, the authors discussed the methodology of the study,
      presented the results of the literature analysis, and the description and
      characteristics of the clinical units, experts interviewed, and of the collegial
      and collaborative RNMD relationships found in the 5 participating hospitals. Part
      2 analyzes the extent to which the 5 structures identified by the National Joint
      Practice Commission as necessary for RNMD collaboration are present in the 5
      hospitals, the structures identified by the experts in this study, and
      suggestions and implications for management practice.

PMID- 16282830
TI  - Chronic fatigue syndrome, mast cells, and tricyclic antidepressants.

PMID- 16282831
TI  - Sex differences in the subjective tolerability of antipsychotic drugs.
AB  - In recent years, research efforts have been directed to better characterize the
      subjective experience of taking psychotropic drugs. This study investigated the
      sex difference in the subjective tolerability of antipsychotic drugs.
      Participants were recruited from patients under the care of psychiatric services
      serving geographical catchment areas in Croydon (UK), Verona (Italy), Amsterdam
      (Netherlands), and Leipzig (Germany). Clinically unstable patients with a
      clinical diagnosis of schizophrenia and a research diagnosis of schizophrenia,
      established using the Item Group Checklist of the Schedule for Clinical
      Assessment in Neuropsychiatry, were enrolled. Antipsychotic subjective
      tolerability was rated by means of the Liverpool University Neuroleptic Side
      Effect Rating Scale. During the recruitment period, 245 men and 164 women with
      schizophrenia were recruited. In both sexes, the most frequently reported side
      effects were difficulty in concentrating, tiredness, and weight gain; these side
      effects occurred in approximately 50% of men and in up to 70% of women.
      Extrapyramidal and anticholinergic reactions were reported more often by women,
      whereas men reported sexual problems more often. After background group
      differences were controlled for, sex was the strongest determinant of the
      subjective tolerability of antipsychotic drugs. We therefore conclude that sex
      differences in the subjective tolerability of antipsychotic drugs should be taken
      into account in the pharmacological management of patients with schizophrenia.
      Studies should no longer consider men and women as a homogeneous group, given
      that the subjective tolerability of antipsychotic drugs substantially differs
      between sexes.

PMID- 16282832
TI  - Dose-dependent interaction of paroxetine with risperidone in schizophrenic
      patients.
AB  - Augmentation with paroxetine (10-40 mg/d) for antipsychotic treatment may improve
      the negative symptoms in schizophrenic patients but involves a risk of drug-drug
      interaction. We studied the effects of paroxetine on plasma concentrations of
      risperidone and 9-hydroxyrisperidone and their clinical symptoms in risperidone
      treated patients. Twelve schizophrenic inpatients with prevailingly negative
      symptoms receiving risperidone 4 mg/d were, in addition, treated with incremental
      doses of paroxetine for 12 weeks (10, 20, and 40 mg/d for 4 weeks each). Plasma
      concentrations of risperidone and 9-hydroxyrisperidone were quantified with
      liquid chromatography-mass spectrometry mass-mass spectrometry together with
      clinical assessments before and after each phase of the 3 paroxetine doses.
      Risperidone concentrations during coadministration of paroxetine 10, 20, and 40
      mg/d were 3.8-fold (95% confidence interval, 3.2-5.8, P < 0.01), 7.1-fold (95%
      confidence interval, 5.3-16.5, P < 0.01), and 9.7-fold (95% confidence interval,
      7.8-22.5, P < 0.01) higher than that before paroxetine coadministration,
      respectively. Active moiety (risperidone plus 9-hydroxyrisperidone) concentration
      was not increased during the paroxetine 10 mg/d (1.3-fold, not significant) or 20
      mg/d (1.6-fold, not significant), but were significantly increased by 1.8-fold
      (95% confidence interval, 1.4-2.7, P < 0.05) during the paroxetine 40 mg/d.
      Significant improvement in negative symptoms was observed from 10 to 40 mg/d of
      paroxetine, whereas scores in extrapyramidal side effects during 20 and 40 mg/d
      of paroxetine were significantly higher than baseline score. This study indicates
      that paroxetine increases plasma risperidone concentration and active moiety
      concentration in a dose-dependent manner. Low-dose coadministration of paroxetine
      with risperidone may be safe and effective in the treatment of schizophrenic
      patients with negative symptoms.

PMID- 16282833
TI  - A 6-month prospective observational study on the effects of quetiapine on sexual
      functioning.
AB  - OBJECTIVE: The aim of this study was to assess the long-term impact of quetiapine
      on sexual functioning of patients with schizophrenia treated in a real practice
      setting. METHODS: This was a multicenter, noncomparative, open-label, and
      naturalistic study conducted in outpatients with a diagnosis of schizophrenia or
      schizophreniform disorder as defined by the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition. Patients were evaluated at baseline, day 15,
      and at the end of months 1, 3, and 6 using the Brief Psychiatry Rating Scale, the
      Clinical Global Impression Severity and Improvement Scales, and the Psychotropic
      Related Sexual Dysfunction Questionnaire. All primary effectiveness analyses were
      based on the intent-to-treat sample and consisted primarily of last-observation
      carried-forward analysis of Psychotropic-Related Sexual Dysfunction
      Questionnaire, Brief Psychiatry Rating Scale, and Clinical Global Impression
      Improvement of Illness Scale. RESULTS: Eighty-six patients were recruited by 19
      investigators, and 82 patients were included in the intent-to-treat sample.
      Psychotropic-Related Sexual Dysfunction Questionnaire total scores for the
      patients decreased progressively and significantly from baseline to the study end
      point. When only patients who initiated quetiapine treatment without being
      switched from another antipsychotic (n = 28) were included in the intent-to-treat
      analysis, Psychotropic-Related Sexual Dysfunction Questionnaire scores remained
      almost unchanged throughout the study. Sexual dysfunction rates, defined as a
      change in the score of any item greater than 0, were 3.7%, 2.4%, 2.4%, and 4.9%
      for decreased libido, delayed ejaculation/orgasm, lack of ejaculation/orgasm, and
      difficulties with erection/lubrication, respectively. Overall, quetiapine was
      efficacious and well tolerated. CONCLUSION: Despite the limitations of the
      design, our results suggest that quetiapine shows a low frequency of sexual
      dysfunction during long-term treatment of patients with schizophrenia or
      schizophreniform disorder in the clinical practice setting.

PMID- 16282834
TI  - A preliminary case series on the use of quetiapine for posttraumatic stress
      disorder in juveniles within a youth detention center.
AB  - Juveniles within the youth justice system have high rates of psychiatric
      morbidity, including posttraumatic stress disorder (PTSD). This case series
      describes 6 young people aged 15 to 17 years within a youth detention center who
      met the criteria for PTSD and reported an improvement in symptoms after 6 weeks
      of treatment with low-dose quetiapine. The primary outcome measure used was the
      Traumatic Symptom Checklist in Children. The dose of quetiapine ranged from 50 to
      200 mg/d; T scores for PTSD symptoms decreased from 75 (SD, +/-5.2; range, 68-82)
      to 54 (SD, +/-7.4; range, 43-62) (P < 0.01). Significant improvements in symptoms
      of dissociation (P < 0.01), anxiety (P < 0.01), depression (P < 0.01), and anger
      (P < 0.05) were also noted over the 6-week evaluation period. Low-dose quetiapine
      was tolerated well, with no persisting side effects or adverse events. Nighttime
      sedation was reported, although this was viewed as beneficial. All young people
      opted to continue with treatment after the assessment period. This preliminary
      case series suggests that juveniles in detention who have PTSD may benefit from
      treatment with quetiapine. Caution is needed in interpreting these findings. Both
      larger open-label and blinded trials are warranted to define the use of
      quetiapine in the treatment of PTSD in the adolescent forensic population.

PMID- 16282835
TI  - Combined treatment with sulpiride and paroxetine for accelerated response in
      patients with major depressive disorder.
AB  - Although serotonin reuptake inhibitors are recommended as first-line agents for
      major depressive disorder, delayed onset of action is problematic, and faster
      effective treatment is needed. Sulpiride, a dopamine-mediated agent, has been
      reported to show faster antidepressant efficacy, and we examined the efficacy of
      adjunctive sulpiride in combination with paroxetine (PAX), compared with PAX
      alone, to clarify whether the combined treatment exerts faster effect. Forty-one
      major depressive disorder patients were enrolled in this 12-week open-label trial
      and were randomly assigned to a PAX (10-40 mg/d) or a PAX (10-40 mg/d) plus
      sulpiride (100 mg/d) group. Assessments included the Montgomery-Asberg Depression
      Rating Scale, the 17-item Hamilton Rating Scale for Depression, and the Zung Self
      rating Depression Scale on an intent-to-treat basis, and safety was also
      monitored. Thirty-three patients completed the study. Both PAX + sulpiride and
      PAX treatments showed a mean reduction in the total Montgomery-Asberg Depression
      Rating Scale score of 34.4 to 5.6 and 32.2 to 10.4, respectively (P < 0.001). The
      combined treatment group had a significantly superior outcome in terms of the
      change in the total Montgomery-Asberg Depression Rating Scale, Hamilton Rating
      Scale for Depression, and Zung Self-rating Depression Scale scores between week 1
      and the study end point (P < 0.05). Median times to response among responders
      alone for the combined treatment and monotherapy were 2 and 6 weeks,
      respectively. Both treatments were well tolerated, with no clinically significant
      differences in safety measures except for an elevation of prolactin in the
      combined treatment group. The combination treatment may be a safe and effective
      strategy for accelerating antidepressant response.

PMID- 16282837
TI  - An open-label study of duloxetine for the treatment of major depressive disorder:
      comparison of switching versus initiating treatment approaches.
AB  - This study compared the stabilized duloxetine dose through approximately 12 weeks
      of treatment in patients initiating duloxetine therapy with that in patients
      switching to duloxetine from selective serotonin reuptake inhibitors or
      venlafaxine. All patients met Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition criteria for major depressive disorder. Patients (n =
      112) exhibiting suboptimal response or poor tolerability to their current
      antidepressant medication (citalopram, escitalopram, fluvoxamine, paroxetine,
      sertraline, or venlafaxine) were switched to duloxetine 60 mg once daily (QD)
      without intermediate tapering or titration ("switching" group). A comparator
      group (n = 137), comprising patients not currently receiving antidepressant
      medication, was randomized to receive duloxetine 30 or 60 mg QD ("initiating"
      group). At the end of week 1, patients receiving 30 mg QD had their dose
      increased to 60 mg QD. During the remainder of the study, each patient's
      duloxetine dose could be titrated on the basis of degree of response within a
      range from 60 to 120 mg QD, with 90 mg QD as an intermediate dose. At the study
      end point, approximately one third of the patients in each treatment group were
      stabilized at each of the 3 studied duloxetine doses (60, 90, and 120 mg QD), and
      the distribution of stabilized doses among patients initiating duloxetine therapy
      did not differ significantly from that observed in patients switching to
      duloxetine. The efficacy of duloxetine in patients switching from selective
      serotonin reuptake inhibitor/venlafaxine did not differ significantly from that
      observed in untreated patients initiating duloxetine therapy (baseline-to-end
      point mean changes: 17-Item Hamilton Rating Scale for Depression total score, 
      13.1 vs. -13.5; Hamilton Rating Scale for Anxiety, -10.6 vs. -10.3; and Clinical
      Global Impression of Severity, -2.22 vs. -2.38, respectively). The rate of
      discontinuation caused by adverse events among patients switched to duloxetine
      was significantly lower than that in patients initiating duloxetine therapy (6.3%
      vs. 16.1%, P = 0.018). Treatment-emergent adverse events occurring in more than
      10% of patients in both treatment groups were nausea, headache, dry mouth,
      insomnia, diarrhea, and constipation. In the first week of therapy, patients
      switched to duloxetine reported significantly lower rates of headache and fatigue
      compared with patients initiating duloxetine. Thus, the efficacy of duloxetine in
      switched patients was comparable to that observed in patients initiating
      duloxetine therapy. Immediate switching from a selective serotonin reuptake
      inhibitor or venlafaxine to duloxetine (60 mg QD) was well tolerated.

PMID- 16282838
TI  - Antidepressants, warfarin, and the risk of hemorrhage.
AB  - BACKGROUND: Case reports suggest that some selective serotonin reuptake
      inhibitors can interact with warfarin to increase the likelihood of bleeding. We
      speculated that, among patients receiving warfarin, initiation of selective
      serotonin reuptake inhibitor treatment would be associated with an increased risk
      of hospitalization for upper gastrointestinal tract bleeding (UGIB). METHODS: We
      conducted a population-based, nested, case-control study involving Ontario
      residents 66 years or older continuously treated with warfarin for at least 1
      year. Cases admitted with UGIB were compared with matched controls (1:10) to
      explore the odds ratio for initiation of various antidepressants within 42, 90,
      and 180 days before the index admission. RESULTS: From January 1994 to December
      2002, we identified 98,784 elderly patients continuously receiving warfarin for
      at least 1 year; of whom 1538 (0.6%) were admitted to hospital for UGIB. The
      adjusted odds ratio for fluoxetine/fluvoxamine exposure in 90 days before UGIB
      hospitalization is 1.2 (95% confidence interval, 0.8-1.7), and the adjusted odds
      ratio for other selective serotonin reuptake inhibitors in the same period was
      1.1 (95% confidence interval, 0.9-1.4). The odds ratios for exposure to
      antidepressants in 180 days before UGIB hospitalization were similar. CONCLUSION:
      The initiation of selective serotonin reuptake inhibitor treatment in patients
      receiving warfarin was not associated with a significant increase in the risk of
      hospitalization for UGIB.

PMID- 16282839
TI  - Assessment of the integrity of study blindness in a pediatric clinical trial of
      risperidone.
AB  - OBJECTIVE: Controlled clinical trials in pediatric psychopharmacology rely on
      blinded parents and clinical evaluators for outcome data, but little is known
      about the success of the masking procedures. The blindness of clinical evaluators
      and parents was examined in a clinical trial of risperidone in autism. METHODS:
      Clinical evaluators and parents were asked to guess individual treatment
      assignments at the end of an 8-week placebo-controlled trial of risperidone in
      children (aged 5-17 years) with autism. Clinical evaluators did not have access
      to adverse event data. RESULTS: The rates of correctly guessing individual
      treatment assignment (risperidone or placebo) were significantly greater than
      chance for both clinical evaluators and parents (P < 0.001). Clinical evaluators
      associated improvement with attribution to risperidone, and lack of improvement
      with attribution to placebo, in both the risperidone and placebo treatment arms.
      Parents associated improvement with attribution to risperidone only in the
      placebo treatment arm. Parents reported that adverse events influenced their
      guesses, but presence of adverse events was not associated with correctness of
      guess. CONCLUSION: Improvement was associated with attribution to active
      treatment regardless of actual treatment assignment, and adverse events did not
      appear to be a threat to study blindness.

PMID- 16282840
TI  - Effects of age and sex on olanzapine plasma concentrations.
AB  - Age and sex may influence both efficacy and side effects of second-generation
      antipsychotics. Women and elderly patients tend to have a higher prevalence for
      several side effects. Higher plasma levels in these groups of patients may be one
      reason. We studied the hypothesis that steady-state olanzapine plasma
      concentrations depend on age and sex. Sixty-seven inpatients on stable olanzapine
      dose were referred to routine therapeutic drug monitoring of olanzapine. Plasma
      levels were determined by high-performance liquid chromatography with
      electrochemical detection. Obtained data were then analyzed by analysis of
      covariance. Olanzapine plasma levels showed a marked sex difference with
      significantly higher mean concentrations in female patients (adjusted mean
      concentrations, 18.5 ng/mL for men and 31.7 ng/mL for women; P = 0.003). On
      average, the weight-corrected concentration/dose ratios shown by women were 33.5%
      higher than those shown by men, irrespective of age. Regarding the effect of age,
      weight-corrected concentration/dose ratios increased by an average of 9.4% per
      decade of life. All results were adjusted for smoking. Comedication did not
      significantly influence these results. In conclusion, age and sex are important
      variables to consider when prescribing olanzapine for women and in the elderly.

PMID- 16282841
TI  - Oxcarbazepine in patients with impulsive aggression: a double-blind, placebo
      controlled trial.
AB  - OBJECTIVE: Impulsive aggression is a common clinically significant symptom, but
      there are few controlled studies evaluating drug treatment. This study evaluated
      oxcarbazepine in patients with impulsive aggression and whether diagnosis or
      other baseline characteristics predict response. METHOD: Eligible outpatients had
      clinically significant impulsive aggression, without other psychiatric symptoms
      clearly requiring treatment. Patients were randomized to oxcarbazepine or
      placebo, double-blind, for 10 weeks, at a variable dose increasing to 1200 mg/d
      if tolerated and to 2400 mg/d if aggression persisted. Primary outcome measures
      were (1) change in a Global Overt Aggression rating derived from the Overt
      Aggression Scale-Modified and (2) patient-rated global improvement. RESULTS: Of
      48 patients, 24 per group, 9 dropped out due to adverse events, but 45 completed
      at least 4 weeks on double-blind medication. Analyses showed consistent evidence
      of benefit from oxcarbazepine, compared with placebo, on both primary efficacy
      measures and most secondary measures. There were no significant interactions
      between diagnosis or other baseline characteristics and differential response to
      oxcarbazepine or placebo. CONCLUSION: Oxcarbazepine appears to benefit adults
      with clinically significant impulsive aggression.

PMID- 16282842
TI  - Mirtazapine treatment of social phobia in women: a randomized, double-blind,
      placebo-controlled study.
AB  - Social phobia is an anxiety disorder characterized by extreme fear and phobic
      avoidance of social and performance situations and by a relatively poor health
      related quality of life. The goal of this study was to compare the efficacy of
      mirtazapine versus placebo in the treatment of patients with social phobia. In
      2004, we conducted a randomized, double-blind, placebo-controlled study of
      mirtazapine in 66 female subjects from the general population meeting the
      criteria for social phobia. The subjects were randomly assigned in a 1:1 manner
      to mirtazapine (n = 33) or placebo (n = 33). The treatment lasted 10 weeks. Seven
      patients dropped out. Primary outcome measures were self-reported changes on the
      Social Phobia Inventory, Liebowitz Social Anxiety Scale, and Health Survey (SF
      36). In comparison with the placebo group and according to the intent-to-treat
      principle, significant differences on the Social Phobia Inventory and Liebowitz
      Social Anxiety Scale scales (all P < 0.001), as well as on most (5 from 8) scales
      of SF-36 (all P < 0.001), were observed in the mirtazapine-treated subjects. All
      patients tolerated mirtazapine relatively well. Mirtazapine appears to be an
      effective agent in the treatment of social phobia in women and in the improvement
      of their health-related quality of life.

PMID- 16282843
TI  - Intramuscular testosterone supplementation to selective serotonin reuptake
      inhibitor in treatment-resistant depressed men: randomized placebo-controlled
      clinical trial.
AB  - BACKGROUND: Treatment-resistant depression is a persistent clinical problem.
      Exogenous testosterone therapy has psychotropic effects and has been proposed as
      an antidepressant supplement, although this strategy has received limited
      systematic study. OBJECTIVE: The aim of the study was to examine the mood effects
      of testosterone supplementation to a serotonergic antidepressant in men with
      treatment-resistant depression. METHOD: Twenty-six healthy adult men with major
      depressive disorder, partial or nonresponse to 2 adequate antidepressant trials
      during the current episode, and currently using a selective serotonin reuptake
      inhibitor were randomized under double-blind conditions to receive intramuscular
      injections of escalating doses of testosterone or placebo, in addition to their
      existing selective serotonin reuptake inhibitor regimen, for 6 weeks. The main
      outcome measure was the Hamilton Rating Scale for Depression score. RESULTS: The
      mean age was 46.4 +/- 10.8 years; mean total testosterone level, 417.5 +/- 197
      ng/dL; mean baseline Hamilton Rating Scale for Depression score, 22.2 +/- 5.2;
      and median duration of the current depressive episode, 6.3 +/- 10.6 years.
      Hamilton Rating Scale for Depression scores decreased significantly in both
      testosterone (8.4) and placebo (7.4) groups. Antidepressant response, defined as
      a 50% decline in Hamilton Rating Scale for Depression score, was achieved by
      53.8% (7/13) in the testosterone group and 23.1% (3/13) in the placebo group (P =
      0.226). CONCLUSION: Both injectable testosterone and placebo supplementation to
      selective serotonin reuptake inhibitor were associated with improvement in mood;
      group differences were not distinguishable in this small sample of predominantly
      eugonadal men with treatment-resistant depression.

PMID- 16282844
TI  - Fluvoxamine affects sildenafil kinetics and dynamics.
AB  - Sildenafil used as oral drug treatment for erectile dysfunction is predominantly
      metabolized by the cytochrome P450 isozyme 3A4. The antidepressant fluvoxamine is
      an inhibitor of cytochrome P450 3A4. In a randomized, double-blind, placebo
      controlled, crossover study, we evaluated the effects of fluvoxamine dosed to
      steady state on the pharmacokinetics and pharmacodynamics of sildenafil. Twelve
      healthy men received oral fluvoxamine or placebo for 10 days (50 mg every day on
      days 1-3; 100 mg every day on days 4-10). On day 11, all participants received a
      single, oral, open-label dose of 50 mg sildenafil, and blood samples were
      collected for analysis of sildenafil plasma concentrations by liquid
      chromatography/mass spectrometry. Concurrently, the effect of sildenafil on
      venodilation induced by a constant dose of sodium nitroprusside was assessed
      using the dorsal hand vein compliance technique. Sildenafil was well tolerated in
      the presence of fluvoxamine. During fluvoxamine, sildenafil exposure (area under
      the curve) significantly increased by 40% (P < 0.001), and its half-life
      increased by 19% (P = 0.034). Concurrently, sodium nitroprusside-induced
      venodilation was significantly augmented by 59% during fluvoxamine compared to
      placebo (P = 0.012). In conclusion, sildenafil kinetics are mildly affected by
      fluvoxamine which translates into an increase in vascular sildenafil effects.
      Whereas the pharmacokinetic changes do not suggest a large clinically relevant
      interaction, it may be prudent to consider a starting dose of 25 mg in patients
      concurrently treated with fluvoxamine.

PMID- 16282846
TI  - Increased cholesterol levels after paroxetine treatment in patients with panic
      disorder.
AB  - Panic disorder (PD) is associated with an increased cardiovascular risk. We
      examined serum cholesterol and plasma catecholamine levels in PD before and after
      paroxetine treatment. The serum cholesterol and plasma catecholamine levels were
      not different between the PD patients and control subjects before the treatment.
      However, the levels of total cholesterol, high-density lipoprotein cholesterol,
      and low-density lipoprotein cholesterol were significantly increased in the 28 PD
      patients after 3 months of paroxetine treatment, whereas the body mass index and
      plasma catecholamine levels were unchanged. Paroxetine should be used cautiously
      for PD patients who have overt or covert cardiovascular disorders.

PMID- 16282845
TI  - Sustained-release bupropion versus naltrexone in the treatment of pathological
      gambling: a preliminary blind-rater study.
AB  - BACKGROUND: Pathological gambling (PG) is a relatively common and highly
      disabling impulse control disorder. A range of psychotherapeutic agents,
      including selective serotonin reuptake inhibitors, mood stabilizers, and opioid
      antagonists, has been shown to be effective in the treatment of PG. The use of
      selective serotonin reuptake inhibitors and opioid antagonists for PG is
      consistent with the observation that PG shares features of both the obsessive
      compulsive spectrum disorders and addictive disorders. The aim of the study is to
      compare the effectiveness of sustained-release bupropion versus naltrexone in the
      treatment of PG. METHODS: Thirty-six male pathological gamblers were enrolled in
      our study. A comprehensive psychiatric diagnostic evaluation was performed at
      baseline on all patients, and patients were screened for symptoms of gambling,
      depression, and anxiety using the South Oaks Gambling Screen, the Hamilton
      Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical
      Global Impression-Severity Scale. In addition, the patients completed self-report
      questionnaires about their demographic status. Patients were randomized in 2
      groups and received either naltrexone (n = 19) or sustained-release bupropion (n
      = 17) for 12 weeks in a parallel fashion. Treatment response was monitored using
      the Clinical Global Impression-Improvement Scale which was performed at weeks 2,
      4, 8, and 12. Patients were also assessed for the presence of gambling behavior
      via an unstructured interview, which was also performed at weeks 2, 4, 6, 8, and
      12. Raters were blind to the study treatment. RESULTS: The majority of patients
      responded well to the drug treatment. Twelve of 17 patients in the sustained
      release bupropion group completed the 12-week study, and 13 of 19 naltrexone
      patients completed the study. Nine (75%) of the 12 completers were rated as full
      responders in the sustained-release bupropion group versus 10 (76%) of 12 in the
      naltrexone group. Three (25%) of 12 completers in the bupropion group were rated
      as partial responders. In the naltrexone group, 3 (23%) of 13 completers were
      rated as partial responders. Full response was defined as the absence of gambling
      for a 2-week duration together with improvement on the Clinical Global Impression
      Improvement Scale. Partial response was defined as a decrease in the frequency of
      gambling behavior and a decrease in the amount of money spent on gambling.
      CONCLUSION: This preliminary study shows that sustained-release bupropion may be
      effective as naltrexone in the treatment of PG. Further studies are needed to
      confirm our findings.

PMID- 16282847
TI  - Characterizations of long-term anxiolytic benzodiazepine prescriptions in veteran
      patients.
AB  - To characterize long-term prescriptions for commonly prescribed anxiolytic
      benzodiazepines to veteran patients and to identify factors associated with high
      daily doses, we analyzed the linked pharmacy and administrative databases from
      New England Veterans Healthcare System (VISN 1). We analyzed treatment episodes
      of 3 months or longer with the 4 most commonly prescribed agents: alprazolam,
      clonazepam, diazepam, and lorazepam. Descriptive statistics and univariate and
      multivariate analyses described the sample and tested associations of
      pharmacological and clinical variables for patients prescribed the top 5% of
      average daily doses ("high-dose" prescriptions). From 16,630 full or partial
      treatment episodes for all 4 agents analyzed within a 42-month window, average
      daily doses were predominantly moderate, age-sensitive, and stable; refill lag
      intervals were short. Patients on "high-dose" prescriptions for the 4 agents
      combined, compared with "middle quartile" dose prescriptions, in adjusted
      analyses, were younger, more likely to have posttraumatic stress disorder (odds
      ratio [OR], 2.6; 95% confidence interval [CI], 2.17-3.13), substance abuse (OR,
      1.50; 95% CI, 1.25-1.80), and anxiety (OR, 1.33; 95% CI, 1.11-1.60) and were more
      likely to be receiving concurrent oxycodone/acetaminophen (OR, 2.05; 95% CI, 1.64
      2.56), anxiolytic benzodiazepine (OR, 1.51; 95% CI, 1.12-2.03), antidepressant
      (OR, 2.15; 95% CI, 1.80-2.58), and neuroleptic (OR, 2.03; 95% CI, 1.69-2.44)
      prescriptions. These results indicate that veteran patients prescribed anxiolytic
      benzodiazepines typically receive modest, nonincreasing doses over long-term
      treatment episodes. However, those on the highest average daily doses, typically
      more than recommended guidelines, are more likely to have clinical diagnoses and
      concurrent prescriptions for psychoactive medications indicative of more complex
      and, perhaps, problematic management.

PMID- 16282848
TI  - Drugs that inhibit oxidation reactions catalyzed by aldehyde oxidase do not
      inhibit the reductive metabolism of ziprasidone to its major metabolite, S
      methyldihydroziprasidone: an in vitro study.
AB  - Ziprasidone is metabolized in 2 sequential reactions to S
      methyldihydroziprasidone, a major circulating metabolite of ziprasidone in
      humans. Aldehyde oxidase catalyzes the first reaction, a reduction of the
      benzisothiazole ring to dihydroziprasidone, and thiol methyltransferase catalyzes
      the second reaction, methylation of the thiophenol group to yield S
      methyldihydroziprasidone. The conversion of ziprasidone to S
      methyldihydroziprasidone was observed in S9 fraction from human livers when
      supplemented with S-adenosylmethionine. In this report, 36 drugs and other
      compounds that had been previously identified as in vitro inhibitors of human
      liver aldehyde oxidase were assessed for their potential to inhibit ziprasidone
      metabolism to S-methyldihydroziprasidone. Of these drugs, only ketoconazole,
      ondansetron, and tamoxifen demonstrated any inhibition. From these findings, it
      can be concluded that most known inhibitors of human aldehyde oxidase-catalyzed
      oxidation reactions are not inhibitors of ziprasidone reductive metabolism.
      Aldehyde oxidase oxidation and reduction reactions appear to have different
      sensitivities to inhibitors. These data suggest that it is unlikely that aldehyde
      oxidase inhibitors could cause increases in ziprasidone exposure in the clinic.

PMID- 16282849
TI  - Plasma risperidone levels and clinical response in patients with first-episode
      psychosis.

PMID- 16282850
TI  - Respiratory dyskinesia as discontinuation effect of risperidone.

PMID- 16282851
TI  - "Extended" antipsychotic dosing: rationale and pilot data.

PMID- 16282852
TI  - The prevalence of hyperprolactinemia after long-term haloperidol use in patients
      with chronic schizophrenia.

PMID- 16282853
TI  - Delusional disorder with delusions of parasitosis and jealousy after stroke:
      treatment with quetiapine and sertraline.

PMID- 16282854
TI  - Periodic restless legs syndrome associated with quetiapine use: a case report.

PMID- 16282855
TI  - Lisinopril may augment antidepressant response.

PMID- 16282856
TI  - Extrapontine myelinolysis resembling neuroleptic malignant syndrome.

PMID- 16282857
TI  - Impaired glucose homeostasis after imipramine intake in a diabetic patient.

PMID- 16282858
TI  - Diplopia with citalopram: a case report.

PMID- 16282859
TI  - How safe is long-term benzodiazepine pharmacotherapy?

PMID- 16282860
TI  - Understanding toxidromes: serotonin toxicity: a commentary on Montanes-Rada et
      al.

PMID- 16282863
TI  - Modafinil-induced irritability and aggression? A report of 2 bipolar patients.

PMID- 16282861
TI  - Comments on article by Albers et al: "Low-dose fluvoxamine as an adjunct to
      reduce olanzapine therapeutic dose requirements: a prospective dose-adjusted drug
      interaction strategy".

PMID- 16282869
TI  - Associations between submicrometer particles exposures and blood pressure and
      heart rate in patients with lung function impairments.
AB  - OBJECTIVE: The objective of this study was to evaluate whether submicrometer
      particle is associated with elevated blood pressure (BP) and heart rate (HR).
      METHODS: We measured ambulatory systolic BP (SBP), diastolic BP (DBP), and HR
      using a portable BP monitoring system and number concentrations of submicrometer
      particle with a size range of 0.02 to 1 microm (NC0.02-1) by a P-TRAK Ultrafine
      Particle Counter for 10 patients with lung function impairments. RESULTS: We
      found NC0.02-1 exposures at 1- to 3-hour moving averages were associated with the
      elevation of SBP, DBP, and HR. There were 1.4 to 3.4-mm-Hg increases in SBP, 1.4
      to 2.2-mm-Hg increases in DBP, and 0.3 to 3.5-beats/min increases in HR for
      10,000 particles/cm increases in NC0.02-1 at 1- to 3-hour moving averages.
      CONCLUSIONS: Exposures to submicrometer particles were associated with short-term
      increases in BP and HR in patients with lung function impairments.

PMID- 16282871
TI  - A benefit-cost analysis of a worksite nurse practitioner program: first
      impressions.
AB  - OBJECTIVE: This study aimed to assess the initial impact of an on-site nurse
      practitioner (NP) initiative on the health care costs (HCC) among 4,284 employees
      and their dependents. METHODS: The authors analyzed HCC by two methods. First,
      they compared annualized actual values for the first 6 months of the startup year
      (2004) with those projected for 2004 on the basis of claims paid in 2002 and
      2003. Both aggregate and per-individual HCC were used as the basis for
      comparison. The difference in HCC between projected and observed values for 2004
      was defined as the benefit of the NP program. In a second analysis, HCC were
      calculated using 2003 paid claims for major diagnostic categories (MDC). These
      HCC were compared with those that would have been incurred had off-site care been
      used for the (annualized) number of such patients cared for by the NP in 2004
      with the same MDC. The cost of the NP program was used as the denominator in
      calculating the benefit-to-cost ratio using the savings in HCC estimated by the
      two previously mentioned methods. RESULTS: Annualized cost of the NP program was
      82,716 dollars. Savings in HCC using the first method were 1,313,756 dollars per
      year, yielding a benefit-to-cost ratio of 15 to 1. Using the MDC analysis, the
      ratio was 2.4 to 1. This difference in ratios between the two estimates may
      partly be attributable to effects of other initiatives such as the wellness
      program and the Nurse Health Line. The latter was begun 10 weeks before the NP
      program, is available at all times, and is intended to minimize the need for
      workers and families to seek high-cost care at hospital emergency departments.
      CONCLUSIONS: The first 6 months of a new NP initiative yielded substantial
      reductions in HCC that warrant further analysis over longer periods of
      observation. However, the initial estimates may understate the aggregate value of
      the program because it may also reduce on-site injury and illness patterns and
      improve productivity, end points that were not assessed in this initial snapshot.

PMID- 16282870
TI  - How much does quality mental health care profit employers?
AB  - OBJECTIVE: Employers provide most American mental health benefits and are
      increasingly cost conscious. However, commonplace anxiety and depressive
      disorders have enormous economic and workplace performance costs. METHODS: We
      performed multiple literature searches on several areas of pertinent research
      (and on key articles) covering the past 5 years. RESULTS: Substantial research
      exists about anxiety and depression costs, such as performance and productivity,
      absenteeism, presenteeism, disability, physical disability exacerbation, mental
      health treatment, increased medical care costs, exacerbating of physical illness,
      and studies of mental health care limitations and cost-offset. Research
      addressing the potential value of higher quality mental health care is limited.
      CONCLUSIONS: Commonplace anxiety and depressive disorders are costly in the
      workplace. Employers and researchers remain largely unaware of the value of
      quality care and psychiatric skills. Effective solutions involve the increased
      use of psychiatric skills and appropriate treatment.

PMID- 16282872
TI  - Lost time, absence costs, and reduced productivity output for employees with
      bipolar disorder.
AB  - OBJECTIVE: We sought to evaluate the incremental health-related lost work time
      and at-work productivity loss for employees with bipolar disorder (BPD). METHODS:
      Health-related absence and real productivity output of employees with BPD were
      compared with that of non-BPD and other employee cohorts from a large employer
      database using multivariate regression to control for cohort differences.
      RESULTS: After adjusting for confounding factors, employees with BPD had
      significantly higher absence costs (1,219 dollars) and 11.5 additional lost days
      (P<0.05) per year than those without BPD. Adjusted annual productivity output was
      20% lower for the BPD group (P<0.05). CONCLUSIONS: Employees with BPD are less
      likely to be present for work. When present, their productivity level is similar
      to that of other employees, but over the course of a year, their absence rates
      result in significant productivity losses.

PMID- 16282873
TI  - Chronic obstructive pulmonary disease in patients under age 65: utilization and
      costs from a managed care sample.
AB  - OBJECTIVES: Chronic obstructive pulmonary disease (COPD) affects all adult age
      groups, not just elderly males. We assessed the health care utilization and cost
      impact of COPD in different age groups. METHODS: We compared burden of illness,
      utilization, and charges for younger versus older COPD patients and versus age-
      and gender-matched controls. RESULTS: A total of 16.9% of patients with COPD were
      under age 65. Patients with COPD (n=19,338) had higher comorbidity than age
      matched controls (n=94,384) across all age groups. Younger patients with COPD had
      lower comorbidity scores and fewer hospitalizations but more COPD-related
      emergency services than older patients with COPD. Average COPD-related charges
      were higher for younger patients. Facility-based care was the cost driver across
      all age groups. CONCLUSIONS: COPD is a burden to younger individuals in the
      workforce, who are likely to be enrolled in a commercial health plan.

PMID- 16282874
TI  - Occurrences of leukemia subtypes by socioeconomic and occupational groups in
      Sweden.
AB  - OBJECTIVE: The objective of this study was to examine the associations between
      socioeconomic/occupational factors and histologic subtypes of leukemia. METHODS:
      The Swedish Family-Cancer Database was used to calculate standardized incidence
      ratios for different social classes and occupational groups. RESULTS: The overall
      standardized incidence ratio was close to unity between different socioeconomic
      groups, except for female manual workers with a significantly decreased risk.
      Among male occupations, increased risks were noted for sales agents, seamen, and
      chemical process workers. For female occupations, increased risks were observed
      among mechanics, iron and metalware workers, hairdressers, and launderers and dry
      cleaners. CONCLUSIONS: The present study suggests that socioeconomic/occupational
      factors have a minor effect on the risk of leukemia. Occupational groups with
      possible exposure to organic solvents and other chemicals such as chemical
      process workers, mechanics, iron and metalware workers, and launderers and dry
      cleaners may entail true risk for leukemia.

PMID- 16282875
TI  - Psychosocial work environment exposures as risk factors for long-term sickness
      absence among Danish employees: results from DWECS/DREAM.
AB  - OBJECTIVE: This study examines effects of psychosocial risk factors on long-term
      sickness absence, and investigates possible interactions between psychosocial and
      physical work environment risk factors. METHODS: A total of 5,357 employees were
      interviewed in 2000 regarding work environment and followed up during the
      proceeding 1.5 years regarding onset of long-term sickness absence. RESULTS: Long
      term sickness absence among female employees was associated with role conflict,
      low reward, and poor management quality. Demands for hiding emotions and high
      emotional demands predicted long-term sickness absence among men. No significant
      interactions between psychosocial and physical exposures were found for female or
      male employees. CONCLUSIONS: The study suggests a potential for reducing long
      term sickness absence through interventions targeted toward reducing role
      conflict, and improving reward and management quality among female employees, and
      through reducing emotional demands and demands for hiding emotions among male
      employees.

PMID- 16282876
TI  - Triazine herbicides and epithelial ovarian cancer risk in central California.
AB  - OBJECTIVE: We sought to determine whether women with ovarian cancer have
      increased occupational exposure to triazine herbicides. METHODS: A population
      based case-control study of incident cases (n=256) and random digit-dialed
      control subjects (n=1122) was conducted. Participants were administered telephone
      interviews to obtain agricultural work history. These histories were used with
      the statewide pesticide usage database to calculate cumulative exposure
      estimates. The data were analyzed by stratified analysis and unconditional
      logistic regression techniques. RESULTS: The analysis of ever versus never
      occupational exposure to triazines demonstrated that cases were slightly but not
      significantly more likely to be exposed than control subjects (adjusted
      odds=1.34; 95% confidence interval=0.77-2.33). There was no evidence of a dose
      response relationship between triazines and ovarian cancer (P=0.22). CONCLUSIONS:
      Considered with previous studies and animal laboratory data, the current evidence
      is not persuasive as to the presence or absence of an association between ovarian
      cancer and triazine exposure.

PMID- 16282877
TI  - Agricultural dust exposure and respiratory symptoms among California farm
      operators.
AB  - OBJECTIVE: To study whether dust exposure in California agriculture is a risk
      factor for respiratory symptoms. METHODS: A population-based survey of 1947
      California farmers collected respiratory symptoms, occupational and personal
      exposures. Associations between dust and respiratory symptoms were assessed by
      logistic regression models. RESULTS: The prevalence of persistent wheeze was
      8.6%, chronic bronchitis 3.8%, chronic cough 4.2%, and asthma 7.8%. Persistent
      wheeze was independently associated with dust in a dose-response fashion odds
      ratio, 1.2 (95% confidence interval[CI]=0.8-2.0) and 1.8 (95% CI=1.1-3.2) for low
      and high time in dust. A borderline significant association between chronic
      bronchitis and dust exposure was found. Asthma was associated with keeping
      livestock, but not with dust exposure. CONCLUSIONS: Occupational dust exposure
      among California farmers, only one third of whom tended animals, was
      independently associated with chronic respiratory symptoms.

PMID- 16282878
TI  - The effect of early intervention with sumatriptan tablets on migraine-associated
      productivity loss.
AB  - OBJECTIVE: Impaired performance, which can considerably impact employee output,
      occurs when employees attempt to continue work with inadequate treatment while
      experiencing a migraine episode. This analysis examined productivity loss as a
      result of migraine after treatment with sumatriptan tablets and patients' usual
      non-triptan therapy when pain was mild (early intervention) versus when pain was
      moderate/severe. METHODS: The authors conducted a retrospective analysis of data
      on 6803 migraine days reported by 251 subjects who participated in a clinical
      trial. RESULTS: Although early intervention significantly reduced productivity
      loss compared with treatment when pain was moderate/severe for both sumatriptan
      and non-triptan therapy, productivity loss was consistently lower for sumatriptan
      than non-triptan therapy for all predose pain intensity levels. CONCLUSIONS:
      These findings suggest that the pharmaco-economic benefits of early intervention
      with sumatriptan tablets, like the clinical benefits, exceed those of delayed
      intervention.

PMID- 16282879
TI  - Career risk of hepatitis C virus infection among U.S. emergency medical and
      public safety workers.
AB  - OBJECTIVE: A probabilistic model was used to analyze the cumulative risk of
      occupational hepatitis C virus (HCV) infection among U.S. public safety workers.
      METHODS: A model for the career risk of HCV was developed using the frequency of
      parenteral exposures to blood, the population seroprevalence of HCV, and the risk
      of seroconversion after exposure. Estimates of key input variables were obtained
      from published studies. RESULTS: Calculated estimates of the 30-year risk of
      infection ranged from <0.1% for police, firefighters, and corrections officers to
      1.9% among paramedics and emergency department personnel in high-risk
      communities. Infrequent exposure to high-risk blood seems to present a greater
      risk of infection than more frequent contact to low-risk populations.
      CONCLUSIONS: Use of a probabilistic risk assessment model using published data
      can assist in policy decisions designed to protect the health and safety of
      workers. Further efforts to document the frequency of occupationally acquired HCV
      are needed.

PMID- 16282880
TI  - Nasal effects of a mixture of volatile organic compounds and their ozone
      oxidation products.
AB  - OBJECTIVE: Our objective was to determine if low levels of a mixture of volatile
      organic compounds (VOCs) and their ozone (O3) oxidation products, similar to what
      might be found in "sick buildings," cause nasal irritation and inflammation under
      controlled exposure conditions. METHODS: Healthy, nonsmoking women (n=130)
      completed 2-hour controlled exposures to VOCs, VOCs and O3, and a masked air "MA"
      control in random order at least 1 week apart. VOCs and O3 concentrations were
      approximately 25 mg/m and approximately 40 ppb, respectively. Nasal symptoms were
      rated before, during, and after exposure. Nasal lavage fluid was analyzed for
      polymorphonuclear cells, total protein, interleukin-6, and interleukin-8.
      RESULTS: We found no significant differences in symptoms or markers of nasal
      inflammation between exposure conditions. CONCLUSIONS: Results suggest that VOCs
      and their oxidation products may not cause acute nasal effects at low
      concentrations.

PMID- 16282881
TI  - Risk factors for tuberculin skin test positivity in an industrial workforce
      results of a contact investigation.
AB  - OBJECTIVE: The objective of this study was to determine the prevalence of and
      risk factors for tuberculin skin test (TST) positivity among an industrial
      workforce employing many foreign-born workers after one employee was hospitalized
      for active tuberculosis (TB). METHODS: A contact investigation was performed. We
      used crude odds ratios and a multivariate model to assess risk factors for TST
      positivity. RESULTS: The rate of TST positivity was 37.1% (N=97). Twenty-nine of
      36 (80.6%) workers from higher TB prevalence countries versus seven of 61 (11.5%)
      workers born in low-prevalence countries were positive. Workplace risk factors
      included using the lunchroom, carpooling with the case, or working on the same or
      subsequent shift. A total of 66.7% of immigrant workers denied previous
      screening. CONCLUSION: TB contact investigations should probe into workplace
      transmission. Workplaces with workers from higher TB prevalence countries should
      consider pre-placement TB screening.

PMID- 16282882
TI  - Occupational Medicine Forum.
AB  - The Occupational Medicine Forum is prepared by the ACOEM Occupational and
      Environmental Medical Practice Committee and does not necessarily represent an
      official ACOEM position. The Forum is intended for health professionals and is
      not intended to provide medical or legal advice, including illness prevention,
      diagnosis or treatment, or regulatory compliance. Such advice should be obtained
      directly from a physician and/or attorney.

PMID- 16282885
TI  - Metronomic therapy: it makes sense and is patient friendly.

PMID- 16282887
TI  - Role of GSTM1, GSTP1, and GSTT1 gene polymorphism in ifosfamide metabolism
      affecting neurotoxicity and nephrotoxicity in children.
AB  - The aim of this study was to evaluate the impact of GSTM1, GSTT1, and GSTP1 gene
      polymorphism on urinary excretion of unchanged ifosfamide, 2
      dechloroethylifosfamide (2DCIF), and 3-dechloroethylifosfamide (3DCIF) with
      regard to the incidence of ifosfamide-related nephrotoxicity and neurotoxicity in
      children. The study comprised 76 children (38 girls, 38 boys) ages 9.84 to 210
      months who were being treated for various malignant diseases with ifosfamide. The
      children were enrolled after identification of genotype coding for three classes
      of glutathione S-transferases (GSTM1, GSTT1, and GSTP1) at the initial stage of
      diagnosis. (P) nuclear magnetic resonance spectroscopy was used to analyze the
      urinary excretion of unchanged ifosfamide, 2DCIF, and 3DCIF metabolites on
      consecutive days after the end of the 3-hour infusion of ifosfamide. In children
      with polymorphic locus of the GSTP1 gene compared with children with homozygous
      wild alleles, increased urinary excretion of 3DCIF (P=0.029) and decreased
      creatinine clearance was found (Mann-Whitney P=0.03; median 81.1 mL/min/1.73 m
      vs. 105.0 mL/min/1.73 m, respectively). The authors' multidimensional analysis
      model revealed that besides the total ifosfamide dose and co-administration of
      other toxic drugs, polymorphic locus of GSTP1 gene may be one of the factors
      determining a higher toxicity of the cytostatic agent. The model was construed at
      P=0.029. Moreover, no correlation was found between the GSTM1 or GSTT1 genotype
      and ifosfamide toxicity and the urinary excretion of its metabolites. The results
      of this analysis indicate that individual reactions to ifosfamide can depend on
      inherited genetic polymorphisms, especially associated with the GSTP1 gene coding
      detoxifying enzyme.

PMID- 16282886
TI  - A feasibility trial of antiangiogenic (metronomic) chemotherapy in pediatric
      patients with recurrent or progressive cancer.
AB  - Standard chemotherapeutic drugs, when modified by the frequency and dose of
      administration, can target angiogenesis. This approach is referred to as
      antiangiogenic chemotherapy, low-dose chemotherapy, or metronomic chemotherapy.
      This study evaluated the feasibility of 6 months of metronomic chemotherapy, its
      toxicity and tolerability, surrogate markers of activity, and preliminary
      evidence of activity in children with recurrent or progressive cancer. Twenty
      consecutive children were enrolled and received continuous oral thalidomide and
      celecoxib with alternating oral etoposide and cyclophosphamide every 21 days for
      a planned duration of 6 months using antiangiogenic doses of all four drugs.
      Surrogate markers including bFGF, VEGF, endostatin, and thrombospondin were also
      evaluated. Therapy was well tolerated in this heavily pretreated population.
      Toxicities (predominantly reversible bone marrow suppression) responded to dose
      modifications. Sixty percent of the patients received less than the prescribed 6
      months of therapy due to toxicity (one case of deep vein thrombosis), personal
      choice (1 patient), or disease progression (10 patients). Forty percent of the
      patients completed the 6 months of therapy, resulting in prolonged or persistent
      disease-free status. One quarter of all patients continue to be progression free
      more than 123 weeks from starting therapy. Sixteen percent of patients showed a
      radiographic partial response. Only elevated thrombospondin-1 levels appeared to
      correlate with prolonged response. This oral antiangiogenic chemotherapy regimen
      was well tolerated in this heavily pretreated pediatric population, which showed
      prolonged or persistent disease-free status, supporting the continued study of
      antiangiogenic/metronomic chemotherapy in human clinical trials.

PMID- 16282888
TI  - Pediatric stroke and methylenetetrahydrofolate reductase polymorphisms: an
      examination of C677T and A1298C mutations.
AB  - Although rare in children, stroke is becoming increasingly recognized as an
      important cause of morbidity and mortality with an annual incidence of
      approximately 3 per 100,000 per year. While several studies have documented the
      underlying mechanisms and pathogenesis related to stroke in adults, including
      genetic and acquired prothrombotic conditions, the data available on similar
      conditions in children is limited. Evidence suggests that mutations in
      methylenetetrahydrofolate reductase (MTHFR) appear to be linked with
      hyperhomocysteinemia (HHC) and cerebral-thrombotic events in children. While the
      C677T common missense mutation is the best-characterized MTHFR polymorphism,
      another common missense mutation, A1298C also exists. A recent study of children
      demonstrated that the homozygous form of C677T polymorphism occurred two-times as
      often in those with stroke versus healthy controls. In our retrospective chart
      review of 33 children seen at Children's Hospital of Orange County from January
      1, 2000 to September 30, 2003 with the diagnosis of stroke, we examined both the
      C677T and A1298C polymorphisms for occurrence and type. In the subset (n=21),
      which excluded those with a confounding disorder, we observed a significant
      increase in the frequency of A1298C and C677T homozygosity (0.25 [p=0.01] and
      0.20 [p=0.100], respectively); expected rate: (0.06 and 0.08, respectively). Our
      observed rates of heterozygosity for both MTHFR mutations (0.35 and 0.40,
      respectively) were consistent with expected rates (0.28 and 0.38, respectively).
      In all subjects, homocysteine (HC) levels were normal. The results of our study
      suggest that mutations in MTHFR are associated with pediatric stroke. However,
      additional studies are required to confirm our findings and to determine if this
      relationship is causal.

PMID- 16282889
TI  - A case of primary ovarian lymphoma in a child with high levels of CA125 and CA19
      9.
AB  - Primary ovarian lymphoma is extremely rare in children. The authors report a case
      of primary ovarian lymphoma in a child with high levels of CA125 and CA19-9. To
      their knowledge, this is the first such case to be reported in the literature.

PMID- 16282890
TI  - A case of axillary kaposiform hemangioendothelioma resembles a soft tissue
      sarcoma.
AB  - Kaposiform hemangioendothelioma is a rare, aggressive vascular proliferation in
      children that is clinically and histologically distinct from hemangioma of
      infancy. It is often complicated with Kasabach-Merritt syndrome. The authors
      describe a 2-month-old girl who developed a rapidly enlarging deep subcutaneous
      solid tumor in the left axilla. The tumor size was about 10x7 cm and there was no
      skin change over the mass. The results of laboratory tests were significant for a
      moderate anemia (7.0 g/dL) and a profound thrombocytopenia (3x10/L). The
      preoperative radiologic findings were suspicious for a soft tissue sarcoma with
      scapular erosion. Anemia and thrombocytopenia were corrected by preoperative
      corticosteroid therapy and blood component transfusion. The tumor was excised
      totally and the pathologic findings were consistent with Kaposiform
      hemangioendothelioma. Serial blood examinations showed that the hemoglobin and
      platelet count returned to the normal range after surgery.

PMID- 16282891
TI  - Intracranial plasma cell granuloma: case report and treatment of recurrence with
      methotrexate and 6-mercaptopurine.
AB  - Plasma cell granulomas are a rare form of idiopathic inflammatory pseudotumors
      often characterized by non-neoplastic proliferation of plasma cells, clinically
      mimicking a neoplastic process. Pseudotumors of the central nervous system,
      however, are exceptional and rare. The authors describe a 14-year-old girl with a
      mass lesion extending medially along the cavernous sinus into the right middle
      cranial fossa and pterygopalatine and infratemporal fossae. The authors review
      the current literature and discuss successful treatment with methotrexate and 6
      mercaptopurine after recurrence of disease following radiation therapy and
      steroids.

PMID- 16282892
TI  - Successful treatment of chemoresistant stage 3 neuroblastoma using irinotecan as
      a single agent.
AB  - The authors describe a 1-year-old boy who was diagnosed with neuroblastoma by
      mass screening at age 6 months. The tumor originated from the left
      retroperitoneum and extended over the midline, involving major vessels and
      invading the spine with compression of the spinal cord. Although seven courses of
      chemotherapy consisting of vincristine sulfate, cyclophosphamide, pirarubicin
      hydrochloride, and cisplatin were administered, there was no reduction in tumor
      size or decrease in tumor markers. The patient received irinotecan 180 mg/m per
      day for 3 days. Approximately 3 weeks later the tumor had regressed remarkably,
      and tumor markers normalized after the second course of irinotecan. This therapy
      was given a total of four courses every 4 weeks, with the tumor shrinking
      successively in each session. Four years after treatment there is no sign of
      recurrence and the patient is doing well. This case may be the first report
      showing the dramatic efficacy of irinotecan in the treatment of chemoresistant
      neuroblastoma without the use of other antitumor agents. Irinotecan might be a
      promising drug in the management of patients with high-risk neuroblastoma.

PMID- 16282893
TI  - Allogeneic bone marrow transplantation for chemotherapy-refractory hepatosplenic
      gammadelta T-cell lymphoma: case report and review of the literature.
AB  - Hepatosplenic gammadelta T-cell lymphoma is an uncommon pediatric disease and is
      associated with an aggressive and often fatal course. The authors describe the
      case of an 8-year-old girl who presented with transaminitis and
      hepatosplenomegaly. Liver biopsy and peripheral blood flow cytometry were
      diagnostic of hepatosplenic gammadelta T-cell lymphoma. She was treated with
      multi-agent chemotherapy with cyclophosphamide, vincristine, prednisone,
      doxorubicin, and high-dose methotrexate but failed to achieve durable remission.
      She underwent an allogeneic bone marrow transplant from her HLA-identical brother
      with a preparative regimen including total body irradiation and cyclophosphamide.
      She is currently alive and has remained in remission for 30 months after
      transplantation. The authors also review the literature for similar pediatric
      cases.

PMID- 16282894
TI  - Fas expression in lung metastasis from osteosarcoma patients.
AB  - The authors' animal studies have shown that the metastatic potential of
      osteosarcoma (OS) cells correlates inversely with Fas expression-that is, Fas
      negative cells metastasize but Fas-positive cells do not. One reason for this in
      the context of OS lung metastases may be that Fas-positive cells are eliminated
      by engagement with the Fas ligand (FasL) constitutively expressed on the surface
      of pneumocytes, whereas Fas-negative tumor cells are not. The purpose of this
      study was to determine the status of Fas expression in OS lung metastases from
      patients. Specifically, archived paraffin-embedded specimens of lung metastases
      from 38 patients with OS were analyzed by immunohistochemistry. Lung nodules from
      23 of the 38 patients (60%) were Fas negative, those from 12 patients (32%) were
      weakly positive, and that from only 1 patient (3%) was strongly positive.
      Findings in the samples from the remaining two patients (5%) could not be
      interpreted because of extensive necrosis. Most patients with the weakly positive
      tumors and the single patient with the strongly positive tumor received
      chemotherapy prior to lung resection. There was a significant correlation between
      Fas expression and the administration of preoperative salvage chemotherapy (P =
      0.0013). These data indicate that loss of Fas may be one mechanism by which OS
      cells evade host resistance in the lung. Chemotherapy may induce regression by
      upregulating Fas.

PMID- 16282895
TI  - Conservative surgical treatment of a profoundly immunosuppressed pediatric
      patient with Boerhaave syndrome.
AB  - Boerhaave syndrome is a condition described as spontaneous rupture of the
      esophagus that often results in mediastinitis, sepsis, and death. The authors
      report a case of Boerhaave syndrome in a child with acute lymphoblastic leukemia.
      At the time of diagnosis (10 days after rupture), the patient had an absolute
      neutrophil count of 0 and was treated with T-tube drainage of the perforation.
      The T-tube was removed 2 months after the operation. The patient has required
      three endoscopic esophageal dilatations of a mild esophageal stricture. He
      remains in remission from his leukemia, has normal growth and development, and is
      on a regular diet.

PMID- 16282896
TI  - Homozygous hemoglobin Abruzzo in a North American child.
AB  - Hemoglobin Abruzzo is a stable hemoglobin variant with increased oxygen affinity,
      clinically causing compensatory erythrocytosis in affected patients.
      Heterozygosity of this variant with or without beta-thalassemia has been
      previously described in three Italian families, thereby suggesting a single
      origin of the mutation. The authors report the first case of homozygosity in a
      North American female infant, born to heterozygous parents as a product of
      consanguineous marriage.

PMID- 16282897
TI  - Peutz-Jeghers syndrome and bilateral ovarian tumors in a 14-year-old girl.
AB  - The authors describe a 14-year-old girl with Peutz-Jeghers syndrome who presented
      with progressive abdominal distention. Radiologic investigation revealed large
      polycystic tumors on both ovaries. Bilateral ovariectomy was performed and
      microscopic examination showed mucinous ovarian tumors. The authors discuss the
      increased risk for cancer in patients with the Peutz-Jeghers syndrome and review
      the different ovarian tumors associated with this syndrome. They also stress that
      these patients must be followed not only for gastrointestinal disease but also by
      regular gynecologic examination.

PMID- 16282898
TI  - Multiple spleen and liver abscesses due to Yersinia enterocolitica septicemia in
      a child with congenital sideroblastic anemia.
AB  - In patients with iron overload, opportunistic infections are an underestimated
      risk. Yersinia enterocolitica is a rare organism to be isolated in this setting.
      The authors report a case of disseminated Y. enterocolitica sepsis in a 5-year
      old boy with sideroblastic anemia. Ultrasound examination revealed massive
      ascites, a pseudo-appendicitis, and hypoechogenic lesions corresponding to
      abscess formations in the liver and spleen. The initial antibiotic therapy
      consisted of cefotaxime, gentamicin, and metronidazole, but only treatment with
      ciprofloxacin and meropenem led to defervescence and clinical stabilization. The
      risk of developing uncommon infections in patients with iron overload should be
      acknowledged by all physicians, and the relevance of ultrasound examination is
      emphasized. In this case, only a detailed history revealed that several days
      before the onset of diarrhea, the child was feeding a deer; this is how infection
      was probably acquired.

PMID- 16282899
TI  - Pegfilgrastim in pediatric cancer patients.
AB  - Chemotherapy-induced neutropenia is a major dose-limiting side effect of
      intensive chemotherapy in cancer patients. Recently, pegfilgrastim (a product
      with a long half-life, resulting in once-per-cycle dosage) was introduced to
      prevent neutropenia in adults. The authors report 32 episodes of pegfilgrastim
      use in seven pediatric cancer patients to diminish chemotherapy-induced
      neutropenia. Feasibility was assessed by adherence to treatment protocol and
      safety was assessed by adverse effects. There were only two treatment delays (6%)
      due to neutropenia. No short-term adverse effects were recorded. The use of
      pegfilgrastim is feasible in pediatric cancer patients, without short-term
      adverse effects or major treatment delay due to neutropenia.

PMID- 16282901
TI  - Focal nodular hyperplasia is most common in women of childbearing age.

PMID- 16282900
TI  - Conservative management of sex cord tumors with annular tubules of the ovary in
      women with Peutz-Jeghers syndrome.

PMID- 16282902
TI  - Thoracic CT performance and interpretation in the multi-detector era.
AB  - Multi-detector CT (MDCT), in particular isotropic or nearly isotropic MDCT,
      changes the way in which imagers perform and interpret studies of the thorax. The
      speed of data acquisition enables new clinical applications of MDCT in the areas
      of angiography and dynamic perfusion. Cardiac gating software is available, and
      CT studies of the heart and coronary arteries are now feasible. This review,
      however, focuses on the impact of MDCT on the routine practice of thoracic
      imaging, rather than on newer specific MDCT applications. The topics of scan
      performance and interpretation are related, and MDCT changes each of these areas
      when compared with the era of axial CT.

PMID- 16282903
TI  - Evaluation of the cardiac surgery patient with MSCT.
AB  - Advances in MSCT have enabled assessment of cardiac function and anatomy, and ECG
      gating has allowed increasingly accurate depiction of coronary artery grafts and
      native coronary arteries. These capabilities now offer a comprehensive evaluation
      of the preoperative surgical patient. This essay outlines the important imaging
      issues and opportunities in the evaluation of the cardiac surgery patient.

PMID- 16282904
TI  - The Age of CT Pulmonary Angiography.
AB  - With the introduction of multi detector-row CT (MDCT), computed tomography (CT)
      has been firmly established as the de facto first line test for imaging patients
      with suspected pulmonary embolism (PE). However, remaining concerns regarding
      CT's accuracy for diagnosis of isolated peripheral emboli have prevented the
      unanimous acceptance of this test as the standard of reference for imaging PE.
      Consequently, many patients with a chest CT scan negative for PE undergo
      additional testing for a definitive rule-out of PE, increasing radiation burden,
      risk of complications, and health care cost. After a decade of uncertainty, there
      is now conclusive evidence that computed tomography (CT), if positive, provides
      reliable confirmation of the presence of PE and, more importantly, if negative
      effectively rules out clinically significant PE. Current endeavors to streamline
      and facilitate workflow for CT diagnosis of PE will further improve the
      acceptance, utility, and importance of this test. Thus, rather than seeking
      further confirmation for the accuracy of CT for PE diagnosis, future efforts
      ought to be directed at harnessing the unique strengths of this test. Examples
      include improvements in workflow, CT derivation of right ventricular function
      parameters for triage and prognostication of patients with acute PE, and the
      comprehensive assessment of patients with acute chest pain for PE, coronary
      disease, aortic disease, and pulmonary disease by means of a single, contrast
      enhanced, ECG-synchronized CT scan. At the same time, efforts must be directed at
      refining clinical pathways to ensure appropriate use and avoid overutilization of
      this test.

PMID- 16282906
TI  - Gorham's disease of the chest wall: CT and MR characteristics.
AB  - We report a case of Gorham's disease of the chest wall in a 29-year-old man. A
      chest radiograph showed osteolysis of the left first, second, and third ribs. CT
      and MR images revealed a soft tissue mass around the affected ribs. The mass
      presented as having heterogeneous high signal intensity on T2-weighted MR images,
      and it showed minimal enhancement on contrast-enhanced MR images. A histologic
      specimen obtained by incisional biopsy from the left third rib revealed
      proliferation of lymphangiomatous tissue in the bone marrow. A diagnosis of
      Gorham's disease was made based on these clinical, radiologic, and histologic
      findings.

PMID- 16282905
TI  - Posttransplant lymphoproliferative disorder in a lung transplant recipient.
AB  - The authors describe a case of posttransplant lymphoproliferative disorder (PTLD)
      in a 38-year-old Japanese male patient who had undergone bilateral lung
      transplantation. Chest CT performed on day 109 revealed multiple lung nodules
      measuring approximately 1cm in the left lower lobe. Despite administration of
      anti-fungal agents, follow-up CT performed on day 138 showed bilateral lung
      nodules increased in size and number. Transcutaneous lung biopsy was performed,
      yielding a diagnosis of polymorphic PTLD positive for Epstein-Barr virus (EBV)
      encoded RNA (EBER) and CD20. Treatment with rituximab was successful, resulting
      in decreased size and number of lung nodules. FDG-PET showed no increased
      metabolic activity in the residual nodules. In this case, CT and FDG-PET were
      useful for initial diagnosis and evaluation of treatment response. To the best of
      our knowledge, this is the first report of PTLD in a lung transplant recipient in
      Japan documented in the English literature.

PMID- 16282907
TI  - Subcentimeter large cell neuroendocrine carcinoma of the lung.
AB  - To our knowledge, no report exists of a subcentimeter size large cell
      neuroendocrine carcinoma (LCNEC) of the lung. A 75-year-old man participating in
      a low-dose CT screening program for lung cancer was found incidentally to have a
      partly-solid nodule in the right upper lung. After treatment with antibiotics, a
      repeat CT showed resolution of the nodule, but a new solid nodule measuring 9 x 9
      mm was detected in the left lower lobe. The lesion showed marked enhancement on
      dynamic contrast-enhanced MRI. Video-assisted thoracic surgery and frozen section
      biopsy was suggestive of malignant lesion, resulting in extension of surgery to
      lobectomy with nodal dissection. The final diagnosis was stage IA-LCNEC. The
      estimated volume doubling time of the tumor was 30.1 days. These aggressive
      tumors may rarely have doubling times that overlap with benign processes.

PMID- 16282908
TI  - Acute fibrinous and organizing pneumonia: initial presentation as a solitary
      nodule.
AB  - A 55-year-old man complained of cough and dyspnea. His chest radiograph and CT
      scan revealed a solitary nodule with a diameter of 2 cm, which showed an air
      bronchogram and had a hazy contour. After 3 weeks, the radiologic findings
      changed to diffuse infiltration with small centrilobular nodules, alveolar
      consolidation, and bronchial wall thickening. The alveoli contained numerous
      fibrin balls and organizing tissue, which are typical pathologic features of
      acute fibrinous and organizing pneumonia (AFOP), on histologic examination. We
      report the initial radiologic features of AFOP and suggest that there are some
      radiologic similarities between this condition and cryptogenic organizing
      pneumonia.

PMID- 16282909
TI  - Low-grade fibromyxoid sarcoma: CT, sonography, and MR findings in 3 cases.
AB  - Low-grade fibromyxoid sarcoma (LGFMS) is a distinctive variant of fibrosarcoma
      characterized by deceptively bland histologic features and a paradoxically
      aggressive clinical course. The radiologic finding of this uncommon tumor has not
      been described to date. In this report, 3 cases of LGFMS occurring in axilla,
      chest wall, and pleura are presented with CT, MRI, and sonographic findings.

PMID- 16282910
TI  - Kimura's disease: case report and review of the literature.
AB  - Kimura's disease is a rare, chronic inflammatory disease characterized by
      subcutaneous nodules in the head and neck regions associated with regional
      cervical lymphadenopathy. Following its recognition as a pathologic entity,
      numerous reports have been published detailing the pathogenesis, radiologic
      manifestations, and treatment modalities. An extensive review of the literature
      did not reveal any cases of diffuse thoraco-abdominal lymphadenopathy described
      in relation to Kimura's disease. Hence, the interest in the case discussed here.

PMID- 16282911
TI  - Hard metal lung disease: high resolution CT and histologic correlation of the
      initial findings and demonstration of interval improvement.
AB  - Hard metal lung disease (HMLD) is a rare form of interstitial lung disease caused
      by sensitization to cobalt. It occurs in patients exposed to hard metal (tungsten
      carbide) and in diamond workers who use cobalt-containing polishes. The chest
      radiograph may be normal or show a nodular, reticulonodular, or reticular
      pattern. The high-resolution CT findings have been described in a small number of
      patients. Reported abnormalities include patchy lobular ground glass opacities,
      consolidation, reticulation, centrilobular nodularity, and, occasionally,
      honeycombing.We describe the high-resolution CT findings in a patient with
      pathologically proven HMLD who demonstrated interval improvement in the ground
      glass opacities and persistence of the centrilobular nodules following cessation
      of exposure to hard metal and treatment with corticosteroids. To our knowledge,
      this is the first described case of HMLD with follow-up CT examination.

PMID- 16282912
TI  - PET findings in pulmonary dirofilariasis.
AB  - This case demonstrates hypermetabolic activity in a pulmonary round infarct
      secondary to dirofilariasis. This case further illustrates that pulmonary
      dirofilariasis, like other infectious causes of pulmonary nodules, can be PET
      positive.

PMID- 16282913
TI  - An aneurysm of right-sided aortic arch with mirror-image brachiocephalic
      branching.
AB  - The patient is a 63-year-old man whose right retroesophageal aortic arch with
      mirror-image braciocephalic branching was discovered incidentally on computer
      tomography (CT), performed after a minor motor vehicle accident 12 years ago. The
      size of the aortic arch was normal at that time. The patient had no other
      congenital cardiac anomalies. He has received another CT as a part of the staging
      evaluation for renal cell carcinoma. This showed asymmetric aneurysm of the
      aortic arch measuring 4.9 cm in the widest diameter. The patient is asymptomatic
      and being followed closely with CT scans every 6 months. This represents an
      extremely rare case of an aneurysm of right-sided aortic arch with mirror-image
      brachiocephalic branching. We report the case and provide a short review of the
      relevant literature.

PMID- 16282914
TI  - Mycotic pulmonary artery pseudoaneurysm.
AB  - We report a rare case of a mycotic pulmonary artery pseudoaneurysm that was
      detected on CT examination. The pulmonary artery pseudoaneurysm appeared as a
      rapidly growing enhancing mass without a draining vein and with evidence of
      surrounding acute hemorrhage on CT.

PMID- 16282915
TI  - Intralobar pulmonary sequestration with arterial supply from the coronary
      circulation.
AB  - Pulmonary sequestration is an unusual malformation. It consists of a
      nonfunctioning mass of lung tissue that shows no normal continuity with the
      tracheobronchial tree and derives its arterial blood supply from the systemic
      circulation. The thoracic and abdominal aortas are the most common sites of
      origin of the abnormal nutrient branches. Arterial supply of a sequestration from
      the coronary circulation is extremely rare. We present a case of a right middle
      lobe sequestration deriving its branches from the left coronary artery.

PMID- 16282916
TI  - Neurogenic tumors of the mediastinum and chest wall: MR imaging appearance.
AB  - Various histologic types of neurogenic tumors may originate in the mediastinum
      and chest wall. It is possible to make accurate diagnosis of these tumors by
      using the multiplanar capability and high contrast resolution of MR imaging
      because of these characteristic imaging findings. MR and histologic features of
      these tumors are illustrated and described in this essay.

PMID- 16282918
TI  - Perspective on the STR consensus statement.

PMID- 16282919
TI  - Minority opinion: CT screening for lung cancer.

PMID- 16282927
TI  - Update on rotavirus vaccines.
AB  - Rotavirus was discovered in 1973, and 10 years later the first report of a
      rotavirus vaccine clinical trial appeared. This update reviews the epidemiology
      of rotavirus infections, assesses past and current vaccines and presents ideas
      for implementation of vaccination programs in developed and developing countries.

PMID- 16282928
TI  - Vaccine safety controversies and the future of vaccination programs.
AB  - In the years following the hepatitis B vaccination/multiple sclerosis
      controversy, a number of new issues regarding vaccine safety have been raised, in
      some cases leading to more debate and confusion. Against this background, an
      international group of experts was convened to review the current points of view
      concerning the use of thimerosal as a preservative and its potential risks; the
      suggested link between thimerosal-containing vaccines and acute lymphoblastic
      leukemia; the alleged association between aluminum-containing
      vaccines/macrophagic myofasciitis and general systemic complaints; a possible
      link between vaccination and autoimmune pathology; and a hypothetical link
      between measles-mumps-rubella vaccination and autism. At present, there are no
      data to conclude that childhood vaccines, and in particular hepatitis B vaccine,
      pose a serious health risk or justify a change in current immunization practice.
      However, vaccine "scares" continue to have an international impact on
      immunization coverage. Creating a positive environment for immunization can be
      achieved by repositioning the value of vaccines and vaccination, supported by
      evidence-based information. The role of international organizations, the media,
      and the industry in the implementation of communication strategies was discussed
      and the impact of litigation issues on vaccination was evaluated. The Viral
      Hepatitis Prevention Board confirms its commitment to current recommendations for
      universal and risk group hepatitis B vaccination and further encourages the
      conduct of vaccine safety studies and the dissemination of their results.

PMID- 16282929
TI  - Viral etiology and incidence of acute gastroenteritis in young children attending
      day-care centers.
AB  - BACKGROUND: The purpose of the study was to investigate the frequency, morbidity
      and cause of acute gastroenteritis in children attending day-care centers in
      Denmark. METHODS: Children with acute diarrhea (> or =2 consecutive loose stools
      in 24 hours, with duration of < or =7 days), recruited from 19 day-care centers,
      were included. Gastroenteritis viruses, group A rotavirus, sapoviruses,
      noroviruses and astroviruses were detected with reverse transcription-polymerase
      chain reaction assays. In addition, stool specimens were cultured for bacterial
      pathogens. Children who were brought to the clinic with acute diarrhea underwent
      a medical evaluation, including an estimation of dehydration. RESULTS: Two
      hundred seven children (median age, 20.1 months; range, 9-44 months) were
      enrolled. During the 6-month study period, 98 diarrheal episodes in 95 children
      were reported. Of these, 48 were reported retrospectively in telephone
      interviews. The incidence of acute diarrheal episodes was 0.08 episode per child
      per month. A viral etiologic agent was identified in 69% of cases. Rotaviruses
      were identified in 17 cases (40%), sapoviruses in 8 (19%) and astroviruses in 3
      (7%). One patient had a coinfection with rotavirus and astrovirus. Campylobacter
      jejuni was detected in 2 patients and Clostridium difficile was found in 5
      patients, all coinfected with a virus. In clinical assessments, 9 patients (18%)
      showed signs of dehydration and were given oral rehydration solution; 6 of these
      were hospitalized. CONCLUSIONS: Acute diarrhea among children attending day-care
      centers was common in wintertime. Rotaviruses were, expectedly, the most common
      causative agents, but sapoviruses were second to rotaviruses as etiologic agents
      in this population.

PMID- 16282930
TI  - Immunogenicity and immunologic memory of meningococcal C conjugate vaccine in
      premature infants.
AB  - BACKGROUND: Protein-polysaccharide conjugate vaccines against Neisseria
      meningitidis serogroup C were introduced into the U.K. routine immunization
      schedule in 1999. This study is the first to describe both persistence of
      antibody and evidence for induction of immune memory using meningococcal C
      conjugate (MCC) vaccine in preterm infants. METHODS: Immunogenicity and induction
      of immunologic memory by as MCC vaccine was assessed in premature infants; 62
      preterm and 60 term controls received MCC at the accelerated schedule (2, 3 and 4
      months of age). A meningococcal C polysaccharide challenge was administered at 12
      months of age. RESULTS: Both groups achieved similar protective titers after
      primary immunization that then waned significantly by 1 year of age.
      Postchallenge serum bactericidal activity was significantly lower in preterm
      infants (P = 0.03); 73% of preterm versus 88% of term controls achieved a 4-fold
      rise in serum bactericidal activity (P = 0.07). CONCLUSIONS: MCC vaccine is
      immunogenic and primes for immunologic memory in preterm infants. The decreased
      memory responses in these preterm infants in conjunction with waning clinical
      efficacy data for all U.K. infants suggest a role for a routine booster dose of
      vaccine in all infants receiving MCC, especially those born preterm.

PMID- 16282931
TI  - Nasopharyngeal colonization with heptavalent pneumococcal conjugate vaccine
      serotypes of Streptococcus pneumoniae with prolonged vaccine dosing intervals.
AB  - INTRODUCTION: Universal infant heptavalent pneumococcal conjugate vaccine (PCV-7)
      immunization, dosed near to the originally recommended schedule of a 3-dose
      series in the first 6 months of life, then a booster between 12 and 15 months,
      should reduce nasopharyngeal (NP) carriage of Streptococcus pneumoniae (Spn) PCV
      7 types. The reduced availability of PCV-7 altered immunization schedules,
      particularly for third and fourth PCV-7 doses. We evaluated NP colonization in
      relation to originally recommended intervals and numbers of PCV-7 doses. METHODS:
      Spn from NP cultures of a cohort of 106 normal children, obtained during 20
      months of PCV-7 shortage, were identified and serotyped by standard methods.
      RESULTS: Spn was detected in 153 of 418 cultures (37%). Age, >1 sibling, day-care
      attendance and prolonged PCV-7 dosing intervals were univariate risks for NP
      detection of PCV-7 types. PCV-7 strains comprised 7 of 15 (47%) of Spn before the
      first dose, 28 of 36 (78%) and 27 of 41 (66%), respectively, after the first and
      second dose and then 16 of 36 (44%) and 11 of 25 (44%) after the third and fourth
      doses. The risk of NP colonization with PCV-7 types was higher with intervals of
      >3 months between second and third doses and intervals of >8 months between the
      third and fourth doses. Multivariate analysis showed prolonged interval after the
      second and third PCV-7 doses and day-care attendance as risk factors for NP
      detection of PCV-7 strains. CONCLUSION: Although PCV-7 serotypes were detected
      less after third and fourth PCV-7 doses, longer dosing intervals, particularly in
      day-care attendees, were associated with higher risk of PCV-7 detection in the
      NP.

PMID- 16282932
TI  - Evaluation of a hepatitis A immunization program.
AB  - BACKGROUND: The purpose of this study was to evaluate the effectiveness of a
      hepatitis A vaccine requirement targeted at child-care center attendees 2-5 years
      of age in Maricopa County, AZ. A case-control study conducted before
      implementation in 1997 found that individuals with hepatitis A were 6 times more
      likely to have worked in or attended a child-care center than were matched
      controls, and 40% of hepatitis A cases were attributable to attending or working
      in a child-care center. METHODS: A case-control study was conducted
      postimplementation in 1999. Cases were individuals reported to surveillance staff
      between August 1, 1999 and April 30, 2000. Cases were included if they met the
      Centers for Disease Control and Prevention hepatitis A surveillance case
      definition. Each case (n = 72) was matched to 2 controls (n = 144) based on age
      and neighborhood. RESULTS: Cases were more likely to have had contact with a
      hepatitis A case [odds ratio (OR), 7.04; 95% confidence interval (CI), 1.96,
      25.31] than were their matched controls in the unadjusted analysis. Individuals
      with direct contact with a child-care center (OR 0.221; CI 0.05, 0.99) were
      protected against disease. In the multivariate analysis, contact with a hepatitis
      A case (OR 5.63; CI 1.22, 25.91) was significantly associated with disease, and
      the protective effect of education (OR 0.19; CI 0.06, 0.60) remained significant.
      CONCLUSION: The results of this study suggest the vaccination requirement had
      some impact on the epidemiology of hepatitis A in Maricopa County. The risk
      associated with child-care centers seen in the 1997 study is no longer
      significantly associated with hepatitis A disease.

PMID- 16282933
TI  - Vancomycin elimination in human infants with intrauterine growth retardation.
AB  - BACKGROUND: Intrauterine growth retardation (IUGR) results in substantial
      decrease in nephron number and renal and hepatic organ mass in experimental
      animals and newborn infants. Because the liver and the kidneys are the major
      organs for drug biotransformation and elimination, any decrease in their size and
      function may lead to impaired metabolism and elimination of drugs in newborns
      with IUGR. Our objective was to test the hypothesis that IUGR results in
      prolonged renal elimination of vancomycin in newborns. METHODS: Small for
      gestational age (SGA) infants (n = 20) were matched with appropriate for
      gestational age (AGA) infants (n = 123). Steady state peak and trough serum
      concentrations were used to calculate vancomycin clearance (Cl), volume of
      distribution (Vd) and half-life (t(1/2)) for each subject. Pharmacokinetic
      profiles were compared between groups. RESULTS: Overall, Cl, Vd and t(1/2) of
      vancomycin were the same between groups. However, stratification showed decreased
      Cl in those SGA versus AGA newborns 3-4 weeks old and in those newborns with a
      postconceptional age of 27-29 weeks. There was no difference in Vd, normalized
      for weight, between SGA and AGA babies. The half-life of vancomycin was similar
      across most groups but was prolonged in SGA newborns aged 3-4 weeks. CONCLUSIONS:
      Vancomycin Cl differs between SGA and AGA newborns. This difference is greatest
      early in life and normalizes between groups after the fourth week of life or
      after 29 weeks postconceptionally. Normalized Vd is similar between SGA and AGA
      newborns. The elimination of vancomycin is comparable between SGA and AGA
      infants, except before the fifth week of life, when SGA newborns may eliminate
      the drug more slowly. Specific vancomycin dose recommendations for SGA versus AGA
      neonates may therefore be justified during the first month of life.

PMID- 16282934
TI  - Nonmedical costs associated with rotavirus disease requiring hospitalization.
AB  - BACKGROUND: As the most common cause of severe diarrhea among children, rotavirus
      has a significant economic impact. Previous studies focused on the direct medical
      costs of rotavirus infections; however, nonmedical costs account for the majority
      of the financial burden from this disease. Herein, we report the results from the
      largest prospective study in the United States determining the nonmedical costs
      of severe rotavirus infections. METHODS: Prospective, active, gastroenteritis
      case surveillance was conducted between November 1997 and December 1999 at 3
      pediatric medical centers. Rotavirus infection was identified for 548 children
      admitted between 2 weeks and 5 years of age. Detailed information about
      nonmedical costs during the prehospitalization, hospitalization and
      posthospitalization periods was obtained through interviews. RESULTS: The average
      nonmedical cost per case of rotavirus disease was USD $448.77, including $359.04
      for missed work, $56.66 for transportation, $11.90 for oral rehydration
      solutions, $9.59 for diapers, $6.83 for child care changes, $3.82 for special
      foods and $0.93 for formula changes. More than one-half of these expenses (53%)
      occurred outside the hospitalization period, and 80% of the cost was attributable
      to missed work. CONCLUSIONS: With an estimated 50,000 hospitalizations
      attributable to rotavirus each year in the United States, the nonmedical costs of
      severe rotavirus infections may exceed USD $22 million annually. Previous cost
      effectiveness analyses of rotavirus vaccines substantially underestimated this
      burden, suggesting that the nonmedical costs associated with mild to moderate
      rotavirus disease have been similarly underestimated. These findings are needed
      to assess accurately the cost effectiveness of future rotavirus immunization
      strategies.

PMID- 16282935
TI  - Infection with Simkania negevensis in Brooklyn, New York.
AB  - BACKGROUND: Simkania negevensis is a Chlamydia-like intracellular organism that
      is prevalent in populations from a wide range of geographic areas. The role of
      the organism in respiratory disease in the United States is unknown. OBJECTIVE:
      To study the association between infection with S. negevensis and bronchiolitis,
      pneumonia or asthma in Brooklyn, New York. MATERIALS AND METHODS: Pediatric and
      adult inpatients/outpatients with bronchiolitis, pneumonia or asthma were
      recruited, and a similar number of healthy control subjects were enrolled.
      Nasopharyngeal swabs were obtained for culture of S. negevensis and Chlamydia
      pneumoniae and polymerase chain reaction detection of S. negevensis. Sera were
      obtained for measurement of antibodies to S. negevensis and C. pneumoniae.
      RESULTS: One hundred eighty-eight patients and 110 healthy control subjects were
      enrolled. S. negevensis serologic assays were positive for 18% of patients,
      compared with 29% of control subjects (P = 0.09). S. negevensis DNA was detected
      by PCR for 17% of case subjects and 23% of control subjects (P = 0.25). S.
      negevensis was isolated by culture for 1 patient with bronchiolitis. C.
      pneumoniae IgG and S. negevensis IgG were found to increase with increasing age,
      ie, 14%, 50% and 78% (C. pneumoniae) and 13%, 17% and 33% (S. negevensis) for
      subjects 0-18 months, 18 months-18 years and older than 18 years of age,
      respectively. CONCLUSION: S. negevensis was not a significant respiratory
      pathogen in Brooklyn, NY, during the period of the study.

PMID- 16282937
TI  - Kawasaki disease: infection, immunity and genetics.
AB  - Kawasaki disease is an acute multisystem vasculitic syndrome of unknown etiology
      occurring mostly in infants and children younger than 5 years of age. In
      developed countries, Kawasaki disease is currently the leading cause of acquired
      heart diseases in children. However, it is still a mysterious disease. In this
      article, we reviewed and summarized from the aspects based on infection agents,
      host immune dysregulation and genetic background intended to establish a feasible
      infection-immunogenetic pathogenesis for this mysterious disease and also
      provided the rational strategy to explore optimal treatment of this disease.

PMID- 16282936
TI  - Polymerase chain reaction for diagnosis of human immunodeficiency virus infection
      in infancy in low resource settings.
AB  - BACKGROUND: Diagnosis of human immunodeficiency virus (HIV) is essential for
      accessing treatment. Current HIV diagnostic protocols for infants require
      adaptation and validation before they can be implemented in the developing world.
      The timing and type of HIV assays will be dictated by country-specific
      circumstances and experience from similar settings. The performance of an HIV-1
      DNA polymerase chain reaction (PCR) test, and in particular a single test at 6
      weeks of age, in diagnosing HIV subtype C infection acquired in utero or
      peripartum was assessed. METHODS: A retrospective review of 1825 Amplicor HIV-1
      DNA PCR version 1.5 tests performed between 2000 and 2004 in 2 laboratories in
      Johannesburg, South Africa on 769 effectively non-breast-fed infants from 3
      clinically well characterized cohorts was undertaken. The HIV status of each
      infant was used as the standard against which the HIV PCR results were compared.
      RESULTS: The overall sensitivity and specificity of the HIV PCR test were 99.3
      and 99.5% respectively. A single test was 98.8% sensitive and 99.4% specific in
      the 627 infants tested at 6 weeks of age (58 HIV-infected and 569 HIV
      uninfected). Repeat testing of all positive HIV PCR tests minimized false
      positive results. CONCLUSIONS: In resource-poor settings where HIV PCR testing in
      an environment of good laboratory practice is feasible, a single 6-week HIV DNA
      PCR test can increase identification of HIV-infected children substantially from
      current levels. Further operational research on how best to implement and monitor
      such a diagnostic protocol in specific local settings, especially in breast-fed
      infants, is necessary.

PMID- 16282938
TI  - Immunization against genital human papillomaviruses.

PMID- 16282939
TI  - Diagnosis and management of human papillomavirus infections.

PMID- 16282940
TI  - Acute respiratory distress syndrome in a child with human parvovirus B19
      infection.
AB  - A 6-year-old girl developed shock and multiple organ dysfunction including acute
      respiratory distress syndrome in association with parvovirus B19 infection. The
      diagnosis was based on positive antibodies and the detection of parvovirus 19 DNA
      in serum, bronchial secretions and skin biopsy. It seems likely, but it was not
      proved, that the parvovirus infection caused acute respiratory distress syndrome.

PMID- 16282941
TI  - Hypotonic-hyporesponsive episode in a 7-month-old infant after receipt of
      multiple vaccinations.
AB  - A 7-month-old boy became difficult to arouse, was limp and had blue extremities 8
      hours after immunization with intravenous poliovirus, diphtheria-tetanus toxoids
      acellular pertussis, Haemophilus influenzae type b-hepatitis B virus and
      pneumococcal vaccines. The hypotonic-hyporesponsive episode had resolved by the
      time the infant was seen in an emergency department 1 hour later. The report
      describes hypotonic-hyporesponsive episode, encourages reporting of vaccine
      associated adverse events and discusses prognosis and implications for subsequent
      immunization.

PMID- 16282942
TI  - Adenovirus, adeno-associated virus and Kawasaki disease.
AB  - Clinical similarities and shared seasonality suggested a relationship between
      adenovirus infection and Kawasaki disease. We performed adenovirus serology and
      quantitative polymerase chain reaction for both adenovirus and adeno-associated
      virus in patients with acute Kawasaki disease. No evidence was found to suggest a
      link between either virus and Kawasaki disease.

PMID- 16282943
TI  - Group C and G streptococcal disease among children.
AB  - Nine children with infections caused by group C and G streptococci were
      identified from 1995 through 2004. The children ranged in age from 12 to 18
      years. The infections included 4 children with peritonsillar abscess/cellulitis
      and one child each with perirectal abscess, postoperative wound infection,
      ruptured appendix, septic arthritis and cellulitis/abscess. This study
      demonstrates the propensity of group C and G streptococci to cause disease in
      older children and at sites where the organisms reside normally.

PMID- 16282944
TI  - Human coronavirus NL63 associated with lower respiratory tract symptoms in early
      life.
AB  - Coronavirus NL63 has been identified as a new member of the coronavirus genus,
      but its role as a cause of respiratory disease needs to be established. We
      studied the first episode of lower respiratory tract symptoms in a cohort of
      healthy neonates. NL63 was identified in 6 (7%) of 82 cases and was as frequent
      as other coronaviruses (9%). NL63 was recovered at the onset of symptoms and was
      cleared within 3 weeks in half of the cases. Our data suggests that coronavirus
      NL63 causes lower respiratory tract symptoms and is acquired in early life.

PMID- 16282945
TI  - Changes in laboratory features of 192 children with imported falciparum malaria
      treated with quinine.
AB  - Little is known about changes in laboratory values of children with imported
      falciparum malaria. Of 192 children, 69% had parasitemia of 2% or less and 64%
      had platelets <150 x 10/L. In 20%, parasite counts rose within 12-24 hours of
      starting treatment before falling, whereas the platelet counts dropped in 45% but
      returned to normal levels within 5 days. Hemoglobin values were <10 g/dL in 31%
      at presentation and dropped in 61% at 5-21 days after treatment, but did not fall
      below 6.8 g/dL in any case. Blood cultures were negative in all children.
      Hyponatremia (n = 16), jaundice (n = 4) and hypoglycemia (n = 0) were uncommon.
      Thus most children presented with abnormal laboratory values, which initially
      worsened in a significant proportion, but none required active intervention once
      therapy was initiated.

PMID- 16282946
TI  - Chronic granulomatous disease presenting with eosinophilic inflammation.
AB  - Chronic granulomatous disease (CGD), a rare immunodeficiency, typically presents
      with recurrent infections caused by catalase-positive organisms. We report 2
      patients with CGD who presented with eosinophilic inflammatory conditions
      recognized before the diagnosis of CGD. Both patients had significant urologic
      disease. Physicians should be aware of the association of CGD with eosinophilic
      inflammatory conditions.

PMID- 16282947
TI  - Safety and immunogenicity of palivizumab (Synagis) administered for two seasons.
AB  - To evaluate the safety and immunogenicity of palivizumab, 55 children who
      received palivizumab in the IMpact-RSV trial received 5 monthly doses of 15 mg/kg
      palivizumab (Synagis) during the subsequent year. The single child with an
      antipalivizumab titer of >1/40 had no associated serious adverse events and had
      expected serum palivizumab trough concentrations. Second year palivizumab
      prophylaxis was safe and well-tolerated.

PMID- 16282948
TI  - Rifabutin-associated uveitis in a child.
AB  - Uveitis associated with rifabutin treatment is a well-known adverse effect in
      adults with human immunodeficiency virus infection. In children, however, uveitis
      related to rifabutin has been reported in only a few cases. We present a case of
      rifabutin-associated uveitis in a human immunodeficiency virus-negative child. We
      review the literature and discuss special precautions to be considered when
      children are treated with rifabutin.

PMID- 16282949
TI  - Chest pain and pulmonary lesion in a child with asthma.

PMID- 16282950
TI  - Source of infection in household transmission of culture-confirmed pertussis in
      Brazil.

PMID- 16282952
TI  - Positive Coombs test in postpneumococcal hemolytic-uremic syndrome.

PMID- 16282951
TI  - Extrusion of ventriculoperitoneal shunt catheter through the rectum and
      retrograde meningitis.

PMID- 16282955
TI  - Azithromycin treatment of recurrent respiratory tract infections in children.

PMID- 16282953
TI  - Antifungal and antibacterial resistance profiles between Cambodia and Kenyan
      children with human immunodeficiency virus infections receiving trimethoprim
      sulfamethoxazole prophylaxis.

PMID- 16282957
TI  - The role of endoscopic retrograde cholangiopancreatography and endoscopic
      ultrasound in diagnosis and treatment of acute pancreatitis.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is an important tool for
      diagnosis and therapy in acute and recurrent pancreatitis. While treatment of
      biliary disorders leading to pancreatitis is common practice, over the past
      several years many specialized centers have been directing traditional biliary
      techniques such as sphincterotomy and stenting towards the pancreas. A
      justifiable fear of pancreatitis and other complications has caused many
      endoscopists to shy away from pancreatic endotherapy, but refinements in
      technique, extensive experience, and most notably the routine use of pancreatic
      stenting to prevent post-ERCP pancreatitis has opened up the field and allowed
      for endoscopists in specialized centers around the world to perform diagnostic
      and therapeutic ERCP of the pancreas safely and effectively. In acute gallstone
      pancreatitis, the benefit of therapeutic ERCP including biliary sphincterotomy
      has been proven in randomized controlled trials. There are also data to support
      the role of ERCP directed at the pancreatic sphincters and ducts in treatment of
      acute relapsing pancreatitis due to pancreas divisum, sphincter of Oddi
      dysfunction, smoldering pancreatitis, pancreatic ductal disruptions, and perhaps
      even in evolving pancreatic necrosis. Many causes of apparently idiopathic
      pancreatitis can be discovered after an extensive evaluation with endoscopic
      ultrasound (EUS), magnetic resonance cholangiopancreatography (MRCP) and ERCP
      with sphincter of Oddi manometry. ERCP often allows treatment of the underlying
      cause. Because of the inherent risks associated with ERCP, particularly when
      directed toward the pancreas, the role of ERCP in acute and especially recurrent
      pancreatitis should be primarily therapeutic with attempts to establish diagnosis
      whenever possible by less risky techniques including EUS and MRCP. With the added
      techniques, devices, skill-sets, and experience required, pancreatic endotherapy
      should preferably be performed in high volume tertiary referral settings. ERCP
      for diagnosis and treatment of severe or acute relapsing pancreatitis is also
      best performed using a multidisciplinary approach involving endoscopy,
      hepatobiliary-pancreatic surgery, and interventional radiology.

PMID- 16282958
TI  - Endoscopy for bile duct stones.
AB  - In the era of laparoscopic cholecystectomy and advanced non-invasive imaging
      studies, pre-operative endoscopic retrograde cholangiopancreatography (ERCP) for
      bile duct stones should be reserved for selected patients. ERCP remains the
      therapy of choice for removal of bile duct stones in the post-cholecystectomy
      patient and in patients with intact gallbladders. Bile duct stones can be cleared
      in nearly all patients using endoscopic techniques of sphincterotomy and
      mechanical lithotripsy. Difficult or complex bile duct stones can be
      endoscopically removed in the majority of patients with additional techniques
      such as extracorporeal shock wave lithotripsy, intraductal lithotripsy and/or
      stent placement. In non-operative patients in whom stone clearance cannot be
      achieved, long-term stent placement is a potential option in patients who are not
      candidates for further therapy. Endoscopic therapy may be effective in selected
      patients with intrahepatic biliary stones.

PMID- 16282959
TI  - Endoscopic therapy for gastroesophageal reflux disease.
AB  - Endoscopic therapies aimed to reduce gastroesophageal reflux have gained an
      enormous enthusiasm during the last 5 years when several of them were approved by
      the regulatory agencies and released on the market. These novel therapies
      comprise 3 types of techniques: injection/bulking, plicating/suturing and
      radiofrequency thermal injury. Open-labelled trials performed on proton pump
      inhibitors-responding patients with typical gastroesophageal reflux disease
      (GERD) symptoms have shown an improvement in reflux symptoms during short term
      follow-up. Longer-term data are now available and show disappointing results with
      partial-thickness plications of the cardia. Randomized sham-controlled trials,
      which are essential to proof the efficacy of GERD endotherapy because of a known
      high placebo effect in the management of GERD patients, have been conducted, one
      with radiofrequency and one with polymer injection, and have confirmed the
      clinical efficacy of both techniques, although the clinical benefit was less
      impressive than suggested in open-labelled trials. While mechanistic studies have
      suggested that the compliance of the gastroesophageal junction might be altered
      by GERD endotherapy, objective assessment of acid reflux with ambulatory pH-metry
      has shown, however, minimal or no modification by the treatment. Concerns about
      the safety of these new techniques have raised when complications were reported
      as the number of treated cases increased. Currently, no definite indication is
      established for each technique, but numerous potential indications exist and
      should be addressed in the setting of carefully designed clinical trials.
      Physicians should be patient and wait for proof of efficacy and safety of these
      techniques before using them in their clinical practice. Specific and extensive
      warning should be obtained before starting clinical application. The present
      review aims to provide a comprehensive and critical view of endoscopic therapy in
      GERD management.

PMID- 16282960
TI  - Diverse manifestations and evolving treatments of autoimmune hepatitis.
AB  - Autoimmune hepatitis has a global occurrence and diverse manifestations. Patients
      are frequently asymptomatic (34%), and an acute, even fulminant, presentation is
      possible. Concurrent immune disorders may obscure the liver disease, and
      perivenular (Rappaport zone 3) necrosis is within the histological spectrum.
      Clinical phenotypes and outcomes vary among different ethnic groups, and genetic
      factors strongly affect susceptibility. Non-disease specific autoimmune modifiers
      include female gender and gene polymorphisms that affect immunocyte activation
      and differentiation. Antibodies to soluble liver antigen/liver pancreas may have
      prognostic importance and reflect a genetic propensity for severe disease.
      Subtypes based on serological profiles do not have distinctive outcomes or
      therapies. Variant forms include patients with bile duct injury or loss, absence
      of conventional serological markers, abnormal cholangiograms, or coincidental
      hepatitis C. Treatment is empiric and based on the predominant manifestations
      (hepatitic, cholestatic, or viral). New treatment strategies must be strengthened
      by predictive indices that accurately forecast individual differences in disease
      outcome. Drugs with site-specific actions on immunocyte activation and
      proliferation (cyclosporine, tacrolimus and myco-phenolate mofetil) must be
      assessed by clinical trial, and site-specific molecular interventions (blocking
      peptides, recombinant immune modulators, T cell vaccination, oral tolerance, gene
      silencing and gene therapy) require confident experimental animal models for
      evaluation. Better prognostic indices, new immunosuppressive agents, and site
      specific molecular interventions promise to improve care.

PMID- 16282961
TI  - Developments in diagnosis and treatment of metastatic midgut carcinoid tumors. A
      review.
AB  - Carcinoids are neuroendocrine tumours derived from enterochromaffin cells which
      are widely distributed in the body and may, therefore, arise from any site. They
      are traditionally described as originating from the foregut, midgut and hindgut.
      Localisation in the gastrointestinal tract is the most frequent, among which the
      appendiceal involvement is often found at laparoscopy for appendicitis and the
      small bowel is known for the liver metastases with the production of serotonin
      causing the characteristic carcinoid syndrome with diarrhoea and flushes. The
      overall incidence of carcinoid disease has increased in the past decades, but
      whether this is a true increase or due to early detection or better recognition
      at pathology is not known. The prognosis of metastatic carcinoid tumours has
      improved during the last decade resulting in a 5 year survival of approximately
      50% in the Netherlands. Due to a longer survival, complications such as carcinoid
      heart disease and new metastatic patterns like skin and bone metastases may
      become a more important feature in carcinoid disease. New developments are in the
      field of diagnostics (fine-tuning of the pathology, videocapsule endoscopy to
      find the primary tumour, positron emission tomography [PET] scanning) and
      treatment options (radiofrequency ablation, radioactive octreotide, meta
      iodobenzylguanidine combinations). The new serum marker of carcinoid,
      chromogranin A, may play an important role in the follow-up and NT-proBNP for the
      detection of heart problems. Combining new diagnostic and treatment modalities in
      metastatic carcinoid patients may result in a better quality of life and a longer
      survival. The increasing number of therapeutic options and diagnostic procedures
      requires a multidisciplinary approach focused on tailor-made therapy based on
      patients' specific conditions preferably in specialised centres and in clinical
      studies.

PMID- 16282962
TI  - [Antifungal activity and clinical efficacy of micafungin (funguard)].
AB  - Micafungin (MCFG) is a new lipopeptide antifungal agent of the echinocandin
      class. MCFG inhibits 1,3-beta-D-glucan synthesis in C. albicans and A. fumigatus
      in a non-competitive manner, and has antifungal activity against both Aspergillus
      and Candida species. In neutropenic mouse models of disseminated candidiasis and
      pulmonary aspergillosis, the efficacy of MCFG was superior to that of fluconazole
      and itraconazole, but comparable to that of amphotericin B. The efficacy and
      safety of MCFG were investigated in 70 patients with deep-seated mycosis caused
      by Candida and Aspergillus species. The overall clinical response rates were
      57.1% in aspergillosis and 78.6% in candidiasis. The incidence of adverse events
      related to micafungin was 17.9%, and there was no dose-related occurrence of any
      adverse events. The results from this study indicated that micafungin was
      effective in aspergillosis and candidiasis, with no tolerability problems.

PMID- 16282963
TI  - [Voriconazole-medicalneeds, evidence, potential for the future].
AB  - Voriconazole (VRCZ) is an azole-class antifungal agent with a broad spectrum.
      VRCZ shows high antifungal activity to Candida spp. including fluconazole less
      susceptible species., Aspergillus spp. and Cryptococcus spp. VRCZ shows
      fungicidal activity to Aspergillus spp. In addition, voriconazole shows activity
      to rare pathogens like Fusarium spp. or Scedosporium spp. VRCZ is available in
      both IV and oral formulation. The oral formulation shows stable and almost 100%
      bioavailability. The protein binding ratio is approximately 58% and over 40%
      exists as unbound form. VRCZ shows a good tissue distribution including brain and
      CSF. Outside Japan, several RCTs were conducted for the treatment of deep seated
      mycosis. The results show a very good drug profile superior to the existing
      antifungal agents. VRCZ was approved by the FDA and EMEA in 2002. As of September
      2004, it has been approved in over 50 countries worldwide.

PMID- 16282964
TI  - [Liposomal amphotericin B].
AB  - Liposomal amphotericin B (AmBisome) is a DDS (drug delivery system) formulation
      of amphotericin B (AMPH-B), and has been developed in an attempt to reduce the
      toxicity of AMPH-B while retaining its therapeutic efficacy. AMPH-B has been the
      "gold standard" of antifungal therapy over the past four decades. It has a broad
      spectrum of fungicidal activity against a number of clinically important
      pathogens including Aspergillus and Candida. The mechanism of action of AMPH-B
      involves binding to ergosterol, the principal sterol in fungal cell membranes.
      Binding to ergosterol causes an increase in fungal membrane permeability,
      electrolyte leakage, and cell death. AMPH-B has affinity for cholesterol in
      mammalian membranes, which leads to severe side-effects including kidney damage.
      AmBisome is a unilamellar vesicle composed of AMPH-B and phospholipid. Upon
      administration, AmBisome remains intact in the blood and distributes to the
      tissues where fungal infection may occur, and is disrupted after attachment to
      the outside of fungal cells, resulting in fungal cell death. AmBisome and AMPH-B
      show similar in vitro and in vivo antifungal activity and clinical efficacy.
      However, AmBisome has less infusion-related toxicity and nephrotoxicity than AMPH
      B.

PMID- 16282965
TI  - [Candida adherence and biofilm formation on oral surfaces].
AB  - Candida albicans is the most common fungal opportunistic pathogen in humans. The
      AIDS epidemic, improved life-sustaining therapy, and aggressive anticancer
      therapy have contributed to a rise in the number of severely immunocompromised
      patients. This has led to an increase in oral and systemic fungal infection.
      Several factors, such as adherence, persistence, dimorphism, germ tube formation,
      and/or contact sensing, phenotypic switching, interference with the host defense
      system, synergism with bacteria, and the production of hydrolases or other
      metabolites, have been proposed to be virulence factors of this fungus. Among
      these virulence factors, adherence and persistence are thought to be the most
      important, since the colonization and subsequent biofilm formation of oral
      surfaces may serve as a reservoir for disseminated infections, such as aspiration
      pneumonia and gastrointestinal infection. In the review, we summarized the
      factors involved in the Candida albicans biofilm formation.

PMID- 16282966
TI  - [Cell biology of respiration-deficient mutants of Candida albicans].
AB  - Respiration-deficient (petite) mutation is caused by hereditary impairment in
      mitochondrial functions. Yeasts have been grouped into "petite-positive" and
      "petite-negative" yeasts. Candida albicans has been regarded as a member of the
      petite-negative yeasts in which the respiration deficiency cannot be easily
      induced. We have succeeded in inducing the petite mutation in C. albicans by
      culturing in the presence of a chemical mutagen, acriflavine, at an elevated
      temperature. In the present review, we describe the cell biology of C. albicans
      petite mutants on the basis of experiments performed by our research group:
      namely, on respiratory activity and cytochrome composition, fine structures of
      cells and mitochondria, mitochondrial DNA structure, pathogenicity, oxidative
      stress sensitivity, generation of reactive oxygen species (ROS) and the roles of
      ROS in antifungal actions. We discuss also the usefulness of petite mutants in
      Candida research.

PMID- 16282967
TI  - [ABC transporters of pathogenic fungi: recent advances in functional analyses].
AB  - ABC (ATP binding cassette) transporters consist of transmembrane domains which
      confer specificity, and structurally conserved nucleotide binding domains that
      contain highly conserved amino acid motifs. They act not only as transporters but
      also as receptors or channels that use energy generated by ATP hydrolysis. ABC
      transporters are widely dispersed in nature. They are found in cells ranging from
      prokaryotes (bacteria) to eukaryotes (including humans) and several are
      considered to play crucial roles in cellular homeostasis. Defects in ABC
      transporters in humans are associated with severe diseases such as type 2
      diabetes and cystic fibrosis. Some ABC transporters extrude xenobiotics and
      confer resistance to chemotherapeutics on microbial pathogens and cancer cells.
      Thus ABC transporters are of considerable medical importance. Structure-function
      analysis of ABC transporters has begun to elucidate their mechanisms of substrate
      recognition, the functional regulation of ATP-binding and hydrolysis and to
      identify intrinsic physiological functions. In pathogenic fungi, ABC transporters
      contribute to the clinical problem of drug resistance. The application of new
      technologies to the examination of fungal ABC transporter function is providing
      new insights into the use of antifungal drugs in medical mycology and
      contributing to a better understanding of these important membrane proteins.

PMID- 16282969
TI  - [A case of cutaneous Paecilomyces lilacinus infection on the face].
AB  - A 74-year-old woman presented in April, 2003, with cutaneous lesions of the face
      by Paecilomyces lilacinus infection. The patient had received predonisolone and
      azathioprine for 20 months for treatment of autoimmune hemolytic anemia. The
      lesion first developed on the right lateral eyelid 1.5 years earlier, and
      gradually enlarged. Physical examination revealed a dark reddish or brownish
      plaque and scattered papules and abscesses around the plaque on right lateral and
      lower eyelids, and the cheek. She noted mild tenderness on pressure. Cultures
      obtained from pus and biopsy specimen showed moulds, and those were identified as
      Paecilomyces lilacinus. Griseofulvin, 500 mg per day, was not effective for the
      lesion, so itraconazole, 200-300 mg per day, was administered orally for 11
      weeks. Since culture from pus still yielded P. lilacinus despite clinical
      effectiveness, itraconazole pulse therapy (400 mg daily, 7 days a month) was
      started. The lesion cleared after three cycles of the pulse therapy.

PMID- 16282968
TI  - Intra-species variation of genotypes of Exophiala jeanselmei isolated from
      patients in Japan.
AB  - Isolates of Exophiala jeanselmei have been classified into 15 types based on
      their mitochondrial DNA (mtDNA). Thirteen of the 15 types and E. spinifera, which
      has been classified as E. jeanselmei Type 14, were confirmed to be also clearly
      differentiated by restriction fragment length polymorphism (RFLP) in internal
      transcribed spacer (ITS) regions of ribosomal RNA genes in their nuclear DNA
      (nDNA). Twenty strains of E. jeanselmei, newly identified or isolated from
      patients in Japan, were examined for mtDNA-RFLP and ITS-RFLP. The twenty isolates
      were comprised of: 11 E. jeanselmei Type 5, 6 E. jeanselmei Type 6, 2 Type 10,
      and 1 Type 8. E. jeanselmei Type 6 was the second most common strain in Japan
      after Type 5. Type 5 was definitely identified as E. jeanselmei var. jeanselmei
      and Type 8 was identified as E. jeanselmei var. lecanii-corni based on the
      genotypes of type strains of these species. However, two other types were still
      designated as E. jeanselmei Type 6 and E. jeanselmei Type 10.

PMID- 16282970
TI  - [A case of black dot ringworm caused by Trichophyton tonsurans in Chiba
      Prefecture].
AB  - A 74-year-old woman visited a clinic in Kisarazu, Chiba Prefecture in December
      2002 complaining of itching, scale and alopecia. She had been diagnosed as having
      tinea capitis by a direct microscopic examination of scales, and been treated
      with an antifungal cream and steroid lotion since 1999. The bald area spread from
      frontal to occipital in which multiple black dots and red papules were scattered.
      Abundant endothrix spores were observed in the hair shaft. A mycelial colony was
      isolated from the black dots. A giant colony on Sabouraud's agar was white,
      powdery and flattened with cottony elevation at the center in the obverse, and a
      reddish-brown pigmentation in the reverse. The isolate produced abundant
      microconidia that were round to club-and balloon-shaped with extreme swelling,
      while macroconidia and spiral bodies were few. Hair perforation test was negative
      and urease activity test was positive. ITS1-5.8S-ITS2 rDNA sequencing revealed
      100% homology with T. tonsurans isolated from two old women in Niigata
      Prefecture. On the other hand, 3 bases were different from those of the outbreak
      isolates from judo and wrestling players infected through international matches.
      T. tonsurans has polymorphism and the present isolate might be an autochthonous
      genotype in Japan. This is the first time T. tonsurans was isolated in Chiba
      Prefecture. But this prefecture had been known as an endemic area of Trichophyton
      coccineum, which was very similar in morphological and physiological
      characteristics to those of T. tonsurans before World War II. These facts raise
      the question of whether T. tonsurans has existed in this prefecture before.

PMID- 16282971
TI  - [Trichophyton violaceum infection occurring in a nursing home].
AB  - Six cases of Trichophyton (T.) violaceum infection seen in a nursing home are
      reported. A 66-year-old female (case 1) was found with tinea corporis on her
      face, chest and shoulder, associated with black dot ringworm. A KOH examination
      of hair showed endothrix parasitism. Reddish purple colonies were isolated from
      the patient on Sabouraud's dextrose agar, and intercalary and terminal
      chlamydospores were observed on slide culture. PCR-RFLP analysis of the
      microorganism showed a pattern of T. violaceum type. Therefore, the isolated
      fungus was identified as T. violaceum, a typical anthropophilic dermatophyte
      which had spread among residents and staffs easily. Using a mycological method,
      we examined 59 persons (21 residents and 38 staff members) who had had contact
      with case 1. The results were as follows. An 85-year-old female (case 2) and an
      83-year-old female (case 3) were carriers of T. violaceum. A 23-year-old male
      (case 4) had tinea corporis on his right forearm due to T. violaceum. A 24-year
      old male (case 5) probably had tinea corporis on his right forearm due to T.
      violaceum. One year after case 1's first visit to our clinic, we observed an 88
      year-old female (case 6) of tinea capitis by T. violaceum. It seems that the
      organism was preserved in surroundings and members of the nursing home. The
      contagion in our cases could either have been caused by directly touching the
      person or by sharing their comb. PCR-RFLP analysis was performed within a short
      time, so that we managed effectively to select a way of treatment and to prevent
      the infection from spreading.

PMID- 16282972
TI  - Treatment outcome and relapse with short-term oral terbinafine (250 mg/day) in
      tinea pedis.
AB  - A total of 168 patients with tinea pedis, but without onychomycosis, were treated
      with 1 cycle of terbinafine (TBF) (1 cycle: defined as 250 mg/day for 1 week).
      KOH preparation for direct microscopy was performed 4, 8 and 12 weeks after
      starting therapy to determine if testing was positive for tinea. Patients with no
      negative results on KOH examination or no evidence of obvious clinical
      improvement at 8 weeks, another cycle of the therapy was prescribed. The "cure",
      "no cure", "dropout", and "discontinuation/unevaluable" rates were 89.3%, 4.8%,
      4.8% and 1.2%, respectively. The number of cycles required for cure in the
      plantar type was 1 cycle in 65.9% and 2 cycles in 54.5% of cases; in the
      interdigital type, 1 cycle in 79.1% and 2 cycles in 20.9% of cases; and mixed
      type, 1 cycle in 29.1% and 2 cycles in 60.9% cases. Among patients who were
      followed for at least 3 years after cure, the relapse rates were about 10% each
      year: 1 year, 11.3%; 2 years, 8.9%; and 3 years, 11.2%. The relapse rate of about
      10% each year over a 3-year period suggests that reinfection may be likely.

PMID- 16282973
TI  - Phylogenetic analysis of Histoplasma capsulatum based on partial sequence of the
      D1/D2 region of the 28S rRNA gene.
AB  - In order to confirm the phylogenetic relationships of Histoplasma capsulatum, the
      partial sequences of large subunit (28S) ribosomal gene (D1/D2 region) of 49
      isolates were studied. The similarity values of the 49 isolates were more than
      99.0% across 617 base pairs, however, the 49 isolates were divided into 9 groups.
      These 9 groups were independent of 3 varieties, var. capsulatum, var.
      farciminosum and var. duboisii. These results showed that analysis of the
      nucleotide sequence of the 28S rRNA gene was very effective for identification of
      H. capsulatum and that three varieties of H. capsulatum should be reclassified
      according to the phylogenetic relationship established from analysis of the D1/D2
      region sequences.

PMID- 16282974
TI  - A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity
      specific risk of myocardial infarction.
AB  - Variants of the gene ALOX5AP (also known as FLAP) encoding arachidonate 5
      lipoxygenase activating protein are known to be associated with risk of
      myocardial infarction. Here we show that a haplotype (HapK) spanning the LTA4H
      gene encoding leukotriene A4 hydrolase, a protein in the same biochemical pathway
      as ALOX5AP, confers modest risk of myocardial infarction in an Icelandic cohort.
      Measurements of leukotriene B4 (LTB4) production suggest that this risk is
      mediated through upregulation of the leukotriene pathway. Three cohorts from the
      United States also show that HapK confers a modest relative risk (1.16) in
      European Americans, but it confers a threefold larger risk in African Americans.
      About 27% of the European American controls carried at least one copy of HapK, as
      compared with only 6% of African American controls. Our analyses indicate that
      HapK is very rare in Africa and that its occurrence in African Americans is due
      to European admixture. Interactions with other genetic or environmental risk
      factors that are more common in African Americans are likely to account for the
      greater relative risk conferred by HapK in this group.

PMID- 16282975
TI  - Robust signals of coevolution of interacting residues in mammalian proteomes
      identified by phylogeny-aided structural analysis.
AB  - The structure of a protein depends critically on the complex interactions among
      its amino acid residues. It has long been hypothesized that interacting residues
      might tend to coevolve, but it is not known whether such coevolution is a general
      phenomenon across the proteome. Here, we describe a novel methodology called
      phylogeny-aided structural analysis, which uncovers robust signals of interacting
      residue coevolution in mammalian proteomes. Furthermore, this new method allows
      the magnitude of coevolution to be quantified. Finally, it facilitates a
      comprehensive evaluation of various factors that affect interacting-residue
      coevolution, such as the physicochemical properties of the interactions between
      residues, solvent accessibility of the residues and their secondary structure
      context.

PMID- 16282976
TI  - Myosin IXB variant increases the risk of celiac disease and points toward a
      primary intestinal barrier defect.
AB  - Celiac disease is probably the best-understood immune-related disorder. The
      disease presents in the small intestine and results from the interplay between
      multiple genes and gluten, the triggering environmental factor. Although HLA
      class II genes explain 40% of the heritable risk, non-HLA genes accounting for
      most of the familial clustering have not yet been identified. Here we report
      significant and replicable association (P = 2.1 x 10(-6)) to a common variant
      located in intron 28 of the gene myosin IXB (MYO9B), which encodes an
      unconventional myosin molecule that has a role in actin remodeling of epithelial
      enterocytes. Individuals homozygous with respect to the at-risk allele have a 2.3
      times higher risk of celiac disease (P = 1.55 x 10(-5)). This result is
      suggestive of a primary impairment of the intestinal barrier in the etiology of
      celiac disease, which may explain why immunogenic gluten peptides are able to
      pass through the epithelial barrier.

PMID- 16282977
TI  - Mutations in SIL1 cause Marinesco-Sjogren syndrome, a cerebellar ataxia with
      cataract and myopathy.
AB  - SIL1 (also called BAP) acts as a nucleotide exchange factor for the Hsp70
      chaperone BiP (also called GRP78), which is a key regulator of the main functions
      of the endoplasmic reticulum. We found nine distinct mutations that would disrupt
      the SIL1 protein in individuals with Marinesco-Sjogren syndrome, an autosomal
      recessive cerebellar ataxia complicated by cataracts, developmental delay and
      myopathy. Identification of SIL1 mutations implicates Marinesco-Sjogren syndrome
      as a disease of endoplasmic reticulum dysfunction and suggests a role for this
      organelle in multisystem disorders.

PMID- 16282978
TI  - The gene disrupted in Marinesco-Sjogren syndrome encodes SIL1, an HSPA5
      cochaperone.
AB  - We identified the gene underlying Marinesco-Sjogren syndrome, which is
      characterized by cerebellar ataxia, progressive myopathy and cataracts. We
      identified four disease-associated, predicted loss-of-function mutations in SIL1,
      which encodes a nucleotide exchange factor for the heat-shock protein 70 (HSP70)
      chaperone HSPA5. These data, together with the similar spatial and temporal
      patterns of tissue expression of Sil1 and Hspa5, suggest that disturbed SIL1
      HSPA5 interaction and protein folding is the primary pathology in Marinesco
      Sjogren syndrome.

PMID- 16282979
TI  - Loss of PKD1 and loss of Bcl-2 elicit polycystic kidney disease through distinct
      mechanisms.
AB  - We have recently demonstrated that ablation of one or both alleles of the
      proapoptotic gene Bim prevents the polycystic kidney disease (PKD) that develops
      in mice deficient for the prosurvival protein Bcl-2. The aim of the present study
      was to investigate whether loss of Bim or Bcl-2 could influence the disease in
      the PKD1del34/del34 mutant mice, a model of autosomal dominant PKD.
      PKD1del34/del34 mice were intercrossed with Bim-deficient mice and Bcl-2+/- mice
      to generate double mutants. Loss of Bim does not prevent the development of PKD
      in PKD1del34/del34 mice. On the C57BL/6 genetic background, most older
      PKD1del34/+ mice do not develop PKD, but present with liver cysts. Surprisingly,
      loss of Bim completely prevented liver cysts formation in PKD1del34/+ mice. Loss
      of one Bcl-2 allele did not influence the PKD1del34 phenotype significantly. We
      conclude that loss of PKD1 and loss of Bcl-2 elicit PKD through distinct
      mechanisms.

PMID- 16282980
TI  - A neuroendocrine dysfunction, not testicular mutant ataxin-3 cleavage fragment or
      aggregate, causes cell death in testes of transgenic mice.

PMID- 16282981
TI  - The zebrafish bcl-2 homologue Nrz controls development during somitogenesis and
      gastrulation via apoptosis-dependent and -independent mechanisms.
AB  - Although the role of the b-cell lymphoma (Bcl)-2 family of apoptosis inhibitors
      is well documented in tumor cells and tissue morphogenesis, their role during the
      early development of vertebrates is unknown. Here, we characterize Nrz, a new Bcl
      2-related inhibitor of apoptosis in zebrafish. Nrz is a mitochondrial protein,
      antagonizing the death-accelerator Bax. The nrz gene is mainly expressed during
      gastrulation and somitogenesis. The knockdown of nrz with antisense morpholinos
      leads to alterations of the somites, correlated with an increase in apoptosis. In
      addition, earlier during development, in the zebrafish gastrula, nrz knockdown
      results in an increase of snail-1 expression at the margin and frequent
      gastrulation arrest at the shield stage, independently of apoptosis. Together
      these data suggest that Nrz, in addition to its effect on apoptosis, contributes
      to cell movements during gastrulation by negatively regulating the expression of
      Snail-1, a transcription factor that controls cell adhesion.

PMID- 16282982
TI  - Stress response in mesoangioblast stem cells.
AB  - Stem cells are presumed to survive various stresses, since they are recruited to
      areas of tissue damage and regeneration, where inflammatory cytokines and
      cytotoxic cells may result in severe cell injury. We explored the ability of
      mesoangioblasts to respond to different cell stresses such as heat, heavy metals
      and osmotic stress, by analyzing heat shock protein (HSP)70 synthesis as a stress
      indicator. We found that the A6 mesoangioblast stem cells constitutively
      synthesize HSP70 in a heat shock transcription factor (HSF)-independent way.
      However, A6 respond to heat shock and cadmium treatment by synthesizing HSP70
      over the constitutive expression and this synthesis is HSF1 dependent. The
      exposure of A6 to copper or to a hypertonic medium does neither induce HSP70
      synthesis nor activation of HSF1, while a constitutive binding of constitutive
      heat shock element binding factor was found. Together, these data suggest that
      mesoangioblasts constitutively express HSP70 as an 'a priori' activation
      mechanism, while they maintain the ability to respond to stress stimuli.

PMID- 16282983
TI  - Excitotoxicity mediated by Ca2+-permeable GluR4-containing AMPA receptors
      involves the AP-1 transcription factor.
AB  - Cells preferentially expressing GluR4-containing alpha-amino-3-hydroxy-5-methyl-4
      isoxazole-propionic acid (AMPA) receptors are particularly sensitive to
      excitotoxicity mediated through non-N-methyl-D-aspartate receptors. However, the
      excitotoxic signalling pathways associated with GluR4-containing AMPA receptors
      are not known. In this work, we investigated the downstream signals coupled to
      excitotoxicity mediated by Ca2+-permeable GluR4-containing AMPA receptors, using
      a HEK 293 cell line constitutively expressing the GluR4flip subunit of AMPA
      receptors (HEK-GluR4). Glutamate stimulation of GluR4-containing AMPA receptors
      decreased cell viability, in a calcium-dependent manner, when the receptor
      desensitisation was prevented with cyclothiazide. The excitotoxic stimulation
      mediated through GluR4-containing AMPA receptors increased activator protein-1
      (AP-1) DNA-binding activity. Inhibition of the AP-1 activity by overexpression of
      a c-Jun dominant-negative form protected HEK-GluR4 cells against excitotoxic
      damage. Taken together, the results indicate that overactivation of Ca2+
      permeable GluR4-containing AMPA receptors is coupled to a death pathway mediated,
      at least in part, by the AP-1 transcription factor.

PMID- 16282984
TI  - RNA polyadenylation in Archaea: not observed in Haloferax while the exosome
      polynucleotidylates RNA in Sulfolobus.
AB  - The addition of poly(A) tails to RNA is a phenomenon common to all organisms
      examined so far. No homologues of the known polyadenylating enzymes are found in
      Archaea and little is known concerning the mechanisms of messenger RNA
      degradation in these organisms. Hyperthermophiles of the genus Sulfolobus contain
      a protein complex with high similarity to the exosome, which is known to degrade
      RNA in eukaryotes. Halophilic Archaea, however, do not encode homologues of these
      eukaryotic exosome components. In this work, we analysed RNA polyadenylation and
      degradation in the archaea Sulfolobus solfataricus and Haloferax volcanii. No RNA
      polyadenylation was detected in the halophilic archaeon H. volcanii. However, RNA
      polynucleotidylation occurred in hyperthermophiles of the genus Sulfolobus and
      was mediated by the archaea exosome complex. Together, our results identify the
      first organism without RNA polyadenylation and show a polyadenylation activity of
      the archaea exosome.

PMID- 16282985
TI  - Live-cell imaging of endogenous Ras-GTP illustrates predominant Ras activation at
      the plasma membrane.
AB  - Ras-GTP imaging studies using the Ras-binding domain (RBD) of the Ras effector c
      Raf as a reporter for overexpressed Ras have produced discrepant results about
      the possible activation of Ras at the Golgi apparatus. We report that RBD
      oligomerization provides probes for visualization of endogenous Ras-GTP,
      obviating Ras overexpression and the side effects derived thereof. RBD
      oligomerization results in tenacious binding to Ras-GTP and interruption of Ras
      signalling. Trimeric RBD probes fused to green fluorescent protein report agonist
      induced endogenous Ras activation at the plasma membrane (PM) of COS-7, PC12 and
      Jurkat cells, but do not accumulate at the Golgi. PM illumination is exacerbated
      by Ras overexpression and its sensitivity to dominant-negative RasS17N and
      pharmacological manipulations matches Ras-GTP formation assessed biochemically.
      Our data illustrate that endogenous Golgi-located Ras is not under the control of
      growth factors and argue for the PM as the predominant site of agonist-induced
      Ras activation.

PMID- 16282986
TI  - Phoenix-ampho outperforms PG13 as retroviral packaging cells to transduce human T
      cells with tumor-specific receptors: implications for clinical immunogene therapy
      of cancer.
AB  - We have designed a transgene that encodes a scFv(G250) chimeric receptor, which
      is specific for carboxyanhydrase IX (G250-ligand, G250L), a molecule
      overexpressed by renal cell cancer (RCC). Retroviral transduction of this
      transgene into primary human T lymphocytes confers these cells with specific
      functional responses towards G250L-positive RCC cells. In preparation of a
      clinical phase (I/II) study in RCC patients, we set up a protocol for gene
      transduction and expansion of primary human T cells. For this purpose, we
      directly compared two packaging cell lines, that is, the GALV-pseudotyped MLV
      producing cell line PG13, and the MLV-A-producing cell line Phi-NX-Ampho (a.k.a.
      Phoenix-A). We generated and characterized stable scFv(G250)-positive clones of
      both PG13 and Phoenix cells and optimized the retrovirus production conditions.
      Transductions of primary human T cells yielded 30-60% scFv(G250)+ T cells using
      PG13-derived retrovirus versus up to 90% scFv(G250)+ T cells using Phoenix
      derived retrovirus. The median number of transgene integrations per scFv(G250)+ T
      cell differed only 1.5-fold as determined by real-time PCR (mean number of
      integrations per T cell 2.6 and 3.7 for PG13 and Phoenix-based transductions,
      respectively). In addition, T cells transduced with Phoenix-derived retrovirus
      showed, on a per cell basis, 10-30% higher levels of scFv(G250)-mediated TNFalpha
      production and cytolysis of G250L+ RCC cells than T cells transduced with PG13
      derived retrovirus. The improved functional transduction efficiency together with
      a limited increase in the number of integrations per recipient cell, made us
      select Phoenix clone 58 for our clinical immunogene therapy study.

PMID- 16282987
TI  - mda-7 gene transfer sensitizes breast carcinoma cells to chemotherapy, biologic
      therapies and radiotherapy: correlation with expression of bcl-2 family members.
AB  - Current therapies used in the treatment of breast cancer are limited by systemic
      toxicity, rapid drug metabolism and intrinsic and acquired drug resistance. We
      have previously shown that adenoviral-mediated transfer of the melanoma
      differentiation-associated gene-7 (mda-7) elicits growth inhibition and apoptosis
      in various tumor types. Here, we evaluate the effects of Ad-mda7, alone and in
      combination with other therapies, against a panel of nine breast tumor cell lines
      and their normal counterparts; we report selective Ad-mda7-mediated p53
      independent growth inhibition, G2/M cell cycle arrest, and apoptosis. In vivo, Ad
      mda7 induced p53-independent tumor growth inhibition (P<0.004) in multiple
      xenograft models. We then evaluated the combination of Ad-mda7 with agents
      commonly used to treat breast cancer: radiotherapy (XRT), Tamoxifen, Taxotere,
      Adriamycin, and Herceptin. These agents exhibit diverse modes of action,
      including formation of bulky adducts, inhibition of DNA replication (Adriamycin,
      XRT), damage to microtubules (Taxotere), nonsteroidal estrogen antagonists
      (Tamoxifen), or Her2/neu receptor blockade (Herceptin). Treated with conventional
      anticancer drugs or radiation, MDA-7-expressing cells display additive or
      synergistic cytotoxicity and apoptosis that correlates with decreased BCL-2
      expression and BAX upregulation. In vivo, animals that received Ad-mda7 and XRT
      underwent significant reduction of tumor growth (P<0.002). This is the first
      report of the synergistic effects of Ad-mda7 combined with chemotherapy or
      radiotherapy on human breast carcinoma cells.

PMID- 16282988
TI  - Retrovirus molecular conjugates: a versatile and efficient gene transfer vector
      system for primitive human hematopoietic progenitor cells.
AB  - In principle, transient nongenetic modification of a noninfectious gene transfer
      virus enabling a one time infection and transduction of human cells could
      eliminate the risk of formation of replication competent virus. Formation of a
      molecular conjugate vector by conjugation of noninfective ecotropic murine
      Moloney leukemia virus to polylysine (eMMLV-PL) enabled high-efficiency
      transduction of human HPC using in vitro and in vivo assays. Xenotransplanted NOD
      SCID mice durably expressed the transgene in human leukocytes and human
      progenitor cells with eMMLV-PL achieving three-fold increased transduction
      efficiency when directly compared to optimized amphotropic MMLV (aMMLV)
      transduction. Both aMMLV and eMMLV assembled conjugate vectors showed similar
      transduction efficiency indicating predominant polylysine-mediated uptake.
      Integration of retroviral sequences was determined from individual human HPC
      recovered from eMMLV-PL-xenotransplanted animals. This simple and versatile
      concept of conjugate gene transfer vectors has the potential to enhance
      transduction efficiency as well as to improve certain safety aspects of human
      gene therapy. Moreover, because it permits effective cellular internalization of
      particles, this concept of molecular conjugates can be used as research tool to
      investigate the interactions of otherwise noninfectious viruses or modified viral
      particles at the genomic level.

PMID- 16282991
TI  - Effect of torso shape and heart location in the chest on formation of cardiac
      electric potentials on body surface in dogs.
AB  - Experimental and theoretical methods were employed to study the effects of torso
      shape and heart orientation in the thoracic cavity on peculiarities of the
      formation cardiac electric field on the body surface in dogs. It was found that
      heart orientation to a greater extent than torso shape affected projections of
      cardiac electric potentials from the epicardium onto the body surface.

PMID- 16282990
TI  - Correction of changes in ADP-induced platelet aggregation with vasopressin
      analogue desglycinamide-arginine-vasopressin.
AB  - We studied the effect of vasopressin analogue desglycinamide-arginine-vasopressin
      on changes in platelet hemostasis produced by intragastric administration of
      Ticlid or clopidogrel (inhibitors of ADP-induced platelet aggregation).
      Intranasal administration of the peptide under conditions of hemorrhagic
      diathesis produced a hemostatic effect and normalized some parameters of blood
      coagulation.

PMID- 16282992
TI  - Blood pressure and contractile function of heart ventricles at the early stages
      of hypertonic process.
AB  - In rabbits, arterial hypertension was characterized by progressive elevation of
      systolic and diastolic blood pressure. The contractile function of the left
      ventricle augmented, but its potential working capacity decreased. Opposite
      changes were observed in the right ventricle. It was hypothesized that the
      compensatory mechanisms in the right ventricle during arterial hypertension are
      triggered at the very onset of the pathology, while in the left ventricle they
      develop later.

PMID- 16282993
TI  - Neurosis-associated changes in the granulocytic hemopoietic stem in mice with
      different learning capacity.
AB  - We studied the local mechanisms of neurosis-associated changes in the
      granulocytic hemopoietic stem in CBA/CaLac mice with different learning capacity.
      It was found that in good learners hyperplasia of the bone marrow
      granulocytopoiesis during neurosis was related to enhanced proliferative activity
      and accelerated maturation of granulocyte-macrophage precursors resulting from
      increased formation of granulocytic and erythrogranulocytic hemopoietic islets.
      In poor learners primary suppression of the bone marrow granulocytopoiesis was
      associated with impaired formation of hemopoietic islets (conflict situation) and
      inhibition of differentiation of granulocyte-macrophage precursors (paradoxical
      sleep deprivation followed by T-maze learning). Then, recovered ability of bone
      marrow cells to form granulocyte complexes even against the background of
      inhibition of precursor differentiation (conflict situation) and accelerated
      maturation of granulocytic cells (paradoxical sleep deprivation and maze
      learning) lead to hyperplasia of the granulocytic hemopoietic stem.

PMID- 16282994
TI  - Role of cholinergic structures in individual resistance of rat circulatory system
      to posthemorrhagic hypoxia.
AB  - Experiments employing ultrasound technique showed that nonselective blockade of
      central muscarinic cholinoceptors with amizyl significantly increases the number
      and lifespan of rats highly resistant to acute massive blood loss. This
      pretreatment increased individual resistance of the circulatory system to
      posthemorrhagic hypoxia (blood pressure and portal blood flow rate). Preliminary
      blockade of central nicotinic cholinoceptors and peripheral muscarinic
      cholinoceptors with cyclodol and methacin, respectively, had no effect on the
      percentage of rats highly and low resistant to acute blood loss. Preliminary
      blockade of peripheral muscarinic cholinoceptors with methacin prevented the
      decrease in the cardiac output in low resistant animals during the
      posthemorrhagic period.

PMID- 16282995
TI  - Effect of ubiquinone Q(10) and antioxidant vitamins on free radical oxidation of
      phospholipids in biological membranes of rat liver.
AB  - We studied the effects of 30-day peroral treatment with beta-carotene, a complex
      of antioxidant vitamins (vitamins C and E and provitamin A) and selenium, and
      solubilized ubiquinone Q(10) on the antioxidant potential in rat liver (ascorbate
      dependent free radical oxidation of unsaturated membrane phospholipids). beta
      Carotene irrespective of the administration route increased antioxidant potential
      of the liver by 2-3.5 times. The complex of antioxidant vitamins and selenium
      increased this parameter by more than 15 times. Antiradical activity in rat liver
      was extremely high after administration of solubilized ubiquinone Q(10) (increase
      by more than by 36 times). It can be expected that reduced ubiquinone Q(10) in
      vivo should produce a more pronounced protective effect due to activity of the
      system for bioregeneration of this natural antioxidant.

PMID- 16282996
TI  - Regulatory role of Na,K-ATPase in the growth of heart tissue explants in
      organotypic culture.
AB  - We studied the effects of ouabain, norepinephrine, and acetylcholine on the
      growth of heart tissue explants from 10-12-old chicken embryos in an organotypic
      culture. Ouabain, norepinephrine, and acetylcholine stimulated the growth of
      explants. Our results suggest that trophic function of acetylcholine and
      norepinephrine is associated with regulation of Na,K-ATPase activity as a signal
      transducer.

PMID- 16282997
TI  - Expression of mRNA for inducible NO synthase in human brain.
AB  - We studied expression of inducible NO synthase gene in human brain under
      conditions of acute or chronic intoxication. Acute alcohol intoxication was
      accompanied by changes in enzyme expression in certain brain structures.

PMID- 16282998
TI  - Bemithyl potentiates the antioxidant effect of intermittent hypoxic training.
AB  - The rats were adapted to hypoxic hypoxia by intermittent training in a flow
      pressure chamber for 3 days. The course of bemithyl treatment (25 mg/kg
      intraperitoneally, 3 days) started immediately after the 1st day of training.
      Bemithyl potentiated the adaptive metabolic changes in rat brain induced by
      repeated hypoxic hypoxia, increased the individual resistance to hypoxia, and
      produced a long-lasting effect.

PMID- 16282999
TI  - Neuroprotective properties of afobazol in vitro.
AB  - The effects of a novel selective anxiolytic afobazol on survival of HT-22 neurons
      were studied in the model of oxidative stress and glutamate toxicity. In both
      models, the neuroprotective effect of afobazol was established.

PMID- 16283000
TI  - Effect of licorice root on peripheral blood indexes upon vibration exposure.
AB  - We studied the effect of continuous vibration and treatment with licorice root
      (Glycyrrhiza glabra L.) on peripheral blood red cells in rabbits. Active
      substances of licorice root accelerated metabolism in cells of the bone marrow
      erythroid stem, enhanced compensatory reserve of the organism, and increased
      animal's resistance to stress.

PMID- 16283001
TI  - Pharmacological correction of changes in the lung-placenta system under
      experimental conditions.
AB  - Pathological changes in the fetoplacental complex and lung-placenta system were
      observed in rats with experimental gestosis produced by long-term feeding of a
      high-sodium diet. We revealed a decrease in the weights of the placenta and
      fetus, pulmonary fibrinolytic dysfunction, and increased production of cortisol.
      The course of fraxiparine treatment in animals with experimental gestosis
      decreased coagulation activity of the arterial blood, increased the weights of
      the placenta and fetus, and reduced the concentration of stress hormone cortisol.

PMID- 16283002
TI  - Regulation of reactive oxygen species production by peripheral blood neutrophils
      from women with postpartum endometritis.
AB  - Production of reactive oxygen species in unfractionated peripheral blood
      increased in parturient women without postpartum infectious complications and
      patients with postpartum endometritis. The control group included nonpregnant
      women with normal reproductive function. Intergroup differences were revealed in
      the degree of respiratory burst activation with opsonized zymosan and response of
      isolated granulocytes to chemotactic peptide N-formyl-Met-Leu-Phen (1 muM).
      Production of reactive oxygen species tended to normal after therapy. We studied
      the effects of a specific mitogen-activated protein kinase p38MAPK inhibitor and
      inhibitors of tyrosine protein phosphatases and phosphatidylinositol-3-kinase.
      The role of p38MAPK in reactive oxygen species generation by cells changes
      significantly in parturient women.

PMID- 16283003
TI  - Reactions between human serum gamma-globulin and zinc cations.
AB  - Interactions of human serum gamma-globulin with zinc cations in solution were
      studied by differential spectrophotometry in UV light. Supraphysiological
      concentrations of zinc caused an increment in optical density of protein solution
      reflecting the effect of gamma-globulin saturation with the metal. Zinc
      concentrations below physiological led to hypochromism in the protein absorption
      spectrum. Conformation changes in gamma-globulin during interactions with zinc
      are analyzed for the surface and intramolecular binding sites and are compared
      with the effects of copper cations.

PMID- 16283004
TI  - Circadian dynamics of cell composition of the thymus and lymph nodes in mice
      normally, under conditions of permanent illumination, and after melatonin
      injection.
AB  - The effect of melatonin on disturbed circadian variations in the lymphocyte
      subpopulation composition of the thymus and inguinal lymph nodes was studied in
      CBA mice exposed to constant illumination for 14 days. The desynchronizing effect
      of permanent illumination on the thymus consisted in disappearance of circadian
      variations in the total number of thymocytes, absolute count of thymocytes,
      absolute counts of CD8(+) and CD4(+) cells, and in inversion of changes in the
      absolute counts of CD4(+)8(+) cells from 15.00 to 20.00. In lymph nodes circadian
      variations in the percentage of CD4(+)+ lymphocytes disappeared, while absolute
      counts of CD4(+)8(+) and CD8(+) cells changed from 15.00 to 20.00. Melatonin
      restored circadian dynamics of some parameters mainly in the thymus.

PMID- 16283006
TI  - Immunity parameters in mice of different strains.
AB  - Quantitative composition and functional activity of immunocompetent cells differ
      in mice of different strains. The counts of T cells in the bone marrow and
      spleen, proliferative activity of T cells in the spleen, levels of IL-2 and IL-10
      production by splenic T cells, number of antigen-specific T cells and their
      functional activity are low in C57Bl/6, BALB/c, and CC57W mice and high in
      CBA/CaLac, DBA/2, and C3H animals. Low phagocytic activity of peritoneal
      macrophages was detected in BALB/c and CC57W mice and high activity in C3H
      animals. The content of antibody-producing cells in the spleens of C57Bl/6,
      BALB/c, and CC57W mice is higher than in CBA/CaLac, DBA/2, C3H, A/SN, and AKR/JY
      mice. Functional activity of B cells is lower in BALB/c and CC57W compared to
      CBA/CaLac and DBA/2 mice.

PMID- 16283005
TI  - Role of functional activity of phagocytic mononuclear system in the formation of
      autoprostheses for angioplasty.
AB  - The possibility of formation of connective-tissue vascular prostheses on
      subcutaneously implanted polychlorovynil base was demonstrated in experiments on
      rats. Suppression of the function of phagocytic cell with carrageenan
      decelerates, while its stimulation with tamerit accelerates the formation of
      connective-tissue autoprostheses.

PMID- 16283008
TI  - Vascular endothelium growth factor in the sera of patients with adrenal tumors.
AB  - Serum levels of vascular endothelium growth factor were measured in 43 patients
      with adrenal tumors and 25 healthy subjects. The mean blood levels of the factor
      in patients with adrenal tumors significantly surpassed the control. No
      correlations between the level of vascular endothelium growth factor, patients
      age and sex were detected. The levels of this factor were maximum in patients
      with adrenocortical cancer, but its mean level differed negligibly from that in
      other morphological variants of tumors. The level of vascular endothelium growth
      factor tended to increase with increasing the stage of adrenocortical cancer. A
      direct correlation was revealed between the level of vascular endothelium growth
      factor and tumor size in adrenocortical cancer and aldosterone-producing adenoma.
      Presumably, vascular endothelium growth factor is involved into mechanisms of
      growth, invasion, and metastatic growth of adrenocortical cancer.

PMID- 16283007
TI  - Identification of serovar-specific single-nucleotide polymorphisms of C.
      Trachomatis omp1 gene.
AB  - Complete sequences of omp1 gene encoding chlamydial main outer membrane protein
      were analyzed in 76 clinical strains of C. trachomatis. Thirty-four serovar
      specific single-nucleotide polymorphisms were identified, 20 of them meet two
      criteria: unique position of the nucleotide and unique nucleotide substitution.
      Evaluation of serovar-specific single-nucleotide polymorphisms of omp1 gene can
      appreciably simplify and accelerate genetic diagnosis of C. trachomatis serovars.

PMID- 16283009
TI  - Comparative analysis of the work of morphofunctional zones in normal epithelium,
      fibroadenoma, and cancer of the breast.
AB  - Twenty-four rosettes (proliferative epidermal units) in epithelial tissue are
      united into morphofunctional zones, where cambial cells proliferate with the
      formation of maternal and daughter cells and these latter ones differentiate
      under the influence of electrical field generated by 12 maternal cells. The
      number of cambial cells in morphofunctional zone of a malignant tumor is reduced
      at least 2-fold. Hence, the number of maternal cells is reduced to 6, which is
      insufficient for electric field generation and stimulation of daughter cells
      differentiation. The percentage of cambial cells in a benign tumor decreases 1.5
      times. Daughter cells are differentiated in an electric field whose strength is
      below optimal, but above the threshold value at which cells do not differentiate;
      hence, differentiation is incomplete.

PMID- 16283010
TI  - Carnosine-induced changes in the development of spermatogenic epithelial cells in
      senescence accelerated SAM mice.
AB  - Carnosine significantly increased the number of spermatogonia and Sertoli cells
      in mice prone (SAMP1) and resistant (SAMR1) to accelerated aging and appreciably
      reduced cell yield in meiosis and spermiogenesis in SAMP1 mice. In experimental
      SAMP1 mice catastrophic changes in the number of gametes were paralleled by
      intensive degradation of the spermatogenic epithelium. In SAMR1 mice treated with
      carnosine highly ordered spermatogenic structure was preserved.

PMID- 16283011
TI  - Distribution of (3)H-dopamine and (3)H-DAGO binding sites in the central part of
      rat sinoatrial node.
AB  - Distribution of (3)H-dopamine and (3)H-DAGO binding sites was studied by
      autoradiography on semithin sections of total preparations of rat sinoatrial
      node. The relative density of (3)H-dopamine and (3)H-DAGO binding sites in the
      functional nucleus of the sinoatrial node was minimum and increased in the
      cranial and caudal directions. The level of (3)H-dopamine binding in the
      perinodal atrial myocardium was appreciably lower (22+/-6%), while binding of
      (3)H-DAGO was similar (76+/-16%) to that in the periarterial zone of the
      sinoatrial node.

PMID- 16283012
TI  - Ultrastructural changes in neurons of medullary giant-cell nucleus in growing rat
      exposed to acute stress.
AB  - Ultrastructural transformations in neurons of the medullary giant-cell reticular
      nucleus of young rats during exposure to acute emotional and painful stress
      attest to activation of the protein synthesis system (nucleolar hypertrophy, well
      developed elements of the granular endoplasmic reticulum, increased content of
      free ribosomes and polysomes) in the majority of cells and the appearance of
      organelle injuries in some these cells.

PMID- 16283013
TI  - Changes in the rat thymus cytoarchitectonics during repeated exposure to
      hypergravitation.
AB  - Comparative study of the structural and functional changes in rat thymus after 5
      day and repeated 5-day exposure to hypergravitation (2g) showed less pronounced
      changes after repeated exposure. Proliferative potential of thymic lymphocytes
      was higher and their loss (death) was lower after repeated exposure to
      hypergravitation, which attested to better adaptation of the thymus during
      repeated prolonged exposure to hypergravitation than after single exposure of the
      same intensity and duration. Our findings suggest the possibility of the
      formation of gravitation memory in thymic lymphocytes during repeated long-term
      exposure to hypergravitation.

PMID- 16283014
TI  - Role of capsaicin-sensitive neurons in the regulation of structural organization
      of the thymus.
AB  - Anatomical organization of the thymus was studied in adult Wistar rats after
      injection of a neurotoxic dose of capsaicin. The reaction of the lymphoid
      parenchyma attested to depletion of structural reserves and triggering of
      autoimmunization mechanisms and was associated with accumulation thymocytes with
      morphological signs of apoptosis, Hassals bodies, macrophages, plasmacytes, and
      eosinophils in the subcapsular zone. Through neurokinin and vanilloid receptors
      on the sensory terminals and lymphocytes, capsaicin modulated the level of
      neuropeptides, which seemed to be involved in the regulation of autoimmune
      mechanisms.

PMID- 16283015
TI  - Response of mononuclear phagocyte system to experimental tuberculosis in mice of
      opposite strains.
AB  - Genetically determined peculiarities of the reaction of the mononuclear phagocyte
      system to BCG vaccine manifested in CBA and C57Bl/6 mice by differences in the
      number and size of granulomas and time course of changes in the cellular
      composition of granulomas, peripheral blood, and bone marrow.

PMID- 16283016
TI  - Ultrastructural analysis of secretory granules of myocardial capillary
      endothelium in cardiosurgical stress.
AB  - In patients with chronic myocardial tissue hypoxia irrespective of the disease
      (Fallot's tetralogy, coronary disease) factors of cardiosurgical stress initiate
      a drop of secretory production in coronary capillary endothelium and obstruction
      of the intravascular space by blood cells. In children the peak of exocytosis of
      secretory granules coincides with the period of aortic occlusion, while in adults
      it is attained at the stage of reperfusion.

PMID- 16283017
TI  - Study of regular intracellular and membrane processes in neurons by laser
      interference microscopy.
AB  - Regular fluctuations in the height of phase profile of isolated neuron were
      studied by laser interference microscopy. The resultant spectra of frequencies of
      changes in the phase profile height indicate regular local changes in the optical
      density and/or geometry of neurons. The frequency spectra for the central and pri
      membrane regions of the cells are different.

PMID- 16283018
TI  - [The significance of research in the Brazilian plastic surgery].

PMID- 16283019
TI  - [Research designs].
AB  - The purpose of this study is to analyze the classifications and concepts found in
      the literature regarding the research models on scientific studies commonly used
      in medical articles. This paper provides elements to facilitate the creation of a
      research model. It also helps the researcher to identify which is the research
      model of an article. This article will enable the reader of a scientific paper to
      have a more accurate sense of criticism of the Methods of a study.

PMID- 16283020
TI  - [Developing a study: initial strategy].
AB  - In this article the preparation of a scientific paper and its project are
      described. The possible reasons that lead to rejection of an article such as the
      proper focus of the chosen journal, its writing and mistakes in the grammar are
      considered. The initial steps of a scientific paper such as the choice of an
      idea, literature search, and the selection of related articles are described.
      After a group discussion about the purpose of the paper and its methods
      (brainstorm), the project is described and its items (Introduction, Objective,
      Methods, Protocol, References and Chronogram) are analyzed.

PMID- 16283021
TI  - [Analysis of the topics of a scientific paper].
AB  - The items of a scientific paper are described and its contents are objectively
      analyzed. The title, the most powerful weapon to attract the reader should be
      short and bring up the information regarding the ideas within the article. The
      Introduction situates the reader, showing concisely the relevancy of the study.
      The purpose of the study the main question that should be answered along the
      article--should be written at the end of the Introduction. In Methods, the most
      used types of samples in the medical field are reported and analyzed. The
      different ways to display the Results and the special forms to express the data
      such as the use of tables and graphics are analyzed. The logic of the Discussion,
      respecting the sequence of the items of a scientific paper and the results
      obtained by the author are compared with the literature data. The Abstract
      written by items (structured) and the References and its situation on the text
      are also analyzed.

PMID- 16283022
TI  - [The art of writing a scientific paper].
AB  - The special characteristics of the scientific writing are described in this
      paper. The difficulty of writing of the medical author, the inadequate use of the
      medical jargon and the writing basic rules are analyzed. The author is oriented
      since the initial stage of the writing and how to progressively write his ideas,
      organizing them on a draft and improving the manuscript. Good writing such as the
      use of simple terms, direct order and objectivity which are reported and
      discussed.

PMID- 16283023
TI  - [Photography in medical research].
AB  - Medical photography is an adequate scientific document when performed on a
      standard fashion. A proper photography is an important issue on a scientific
      publication. Plastic surgeons are experts in clinical photography and,
      frequently, an image is a more significant data than the written part of a paper.
      The purpose of this article is to describe the principles developed in this
      specialty. Basic photographic equipment used for clinical pictures is described.
      Standardized pictures determined by patient position and framing using anatomical
      references are reported. Using these rules it is possible to compare pre and post
      operative pictures. Topics such as intra operative pictures in endoscopic
      surgery, computer fotogrametry and in Experimental Surgery are also analyzed.

PMID- 16283024
TI  - [How to choose a journal to submit an article].
AB  - On a submission process, the choice of the journal is a fact that may lead to the
      acceptance or rejection of the paper. Some facts must be considered when a
      journal is chosen. The journal focus, the study type, the scientific value of the
      study, and the innovation that the study will bring to the medical field are
      issues that must be considered when submitting a paper. The data base index and
      the impact factor of the journal are determinant facts that increase the chance
      of citation of the paper. The editorial evaluation process of the journals is
      described and reviewed.

PMID- 16283026
TI  - [Financing of the scientific publication and protection of the scientific
      knowledge].
AB  - The main purpose of a study is its publication on a scientific journal. Research
      financing agencies are important institutions so that studies can be developed
      and published. The most important research financing agencies that are discussed
      in this article are: "Coordenacao de Aperfeicoamento de Pessoal de Nivel
      Superior" (CAPES), "Conselho Nacional de Desenvolvimento Cientifico e
      Tecnologico" (CNPq) and "Fundacao de Amparo a Pesquisa do Estado de Sao Paulo"
      (FAPESP). CAPES' activities can be grouped in four different strategy lines: a)
      it evaluates the stricto sensu, at the post-graduation level; b) it provides
      access and development of scientific research; c) it provides investment on the
      development of high qualified human resources in Brazil and abroad, and d) it
      promotes international scientific cooperation. Although CAPES does not support
      directly scientific publications, almost all actions of this agency contribute to
      the development of scientific research and publication. CNPq has two main
      purposes: financing researches and development of human resources. It provides
      the researchers with financial aid to scientific publication. The grants for
      editing were specifically created for supporting the national scientific and
      technical publications edited by Brazilians institutions or societies. CNPq can
      also support Congresses, Symposiums and similar short-term courses. The
      Plataforma Lattes is also a branch of CNPq on which the Curriculum Lattes is
      available. This site has the curriculum vitae of the scientific community and is
      of great value for researchers. FAPESP also finances journal publications,
      articles and books that bring up original results of studies made by researchers
      from the state of Sao Paulo. It finances, partially, the travel expenses of
      innovative papers authors in meetings within the country or abroad. Brazilian
      authors are increasing the number of international publications. Universities,
      research institutes, financing agencies and private companies are more and more
      concerned with knowledge property. Researchers must understand the need of
      knowledge property and the financing agencies have to consider the patents
      achieved as a criteria of evaluation of scientific production.

PMID- 16283025
TI  - [Experimental models in research].
AB  - The purpose of this study is to collect the main classifications of experimental
      research models and their possible applications in experimental research.
      Literature search was done using the most important data bank available on the
      internet (PUBMED, MEDLINE, SCIELO, LILACS, COCHRANE). A compilation of the
      experimental studies developed at the Plastic Surgery Post Graduate Program of
      the Federal University of Sao Paulo/Paulista School of Medicine was also done.
      Animals models were classified regarding sanitary and genotypical status. The
      understanding of the main classifications of the research experimental models is
      essential to improve and confirm procedures and techniques already described as
      well as the development of new ones.

PMID- 16283027
TI  - [The significance of the South American Society of Cardiology].

PMID- 16283028
TI  - [Cardiac longitudinal study of children perinatally exposed to human
      immunodeficiency virus type 1].
AB  - OBJECTIVE: To determine the frequency of cardiac abnormalities and its natural
      history in children perinatally exposed to HIV-1. METHODS: Eighty-four children
      exposed to HIV-1 were evaluated by serial clinical, electrocardiographic (ECG),
      and Doppler-echocardiographic (ECHO) examinations. RESULTS: Group I-
      (seroreversion)--43 children (51.2%). Absence of clinical abnormalities. ECG:
      incomplete right bundle branch block (RBBB) 5 cases. ECHO: atrial septal defect
      (ASD) and ventricular septal defect (VSD)--1 case each. Group II--41 HIV-infected
      children (48.8%), of whom 51.2% were found to have cardiac abnormalities.
      Asymptomatic or mildly symptomatic children without immunosuppression: no
      clinical and echocardiographic abnormalities; ECG: incomplete right bundle branch
      block (RBBB)--(2 cases). Children with moderate and severe symptoms and
      immunological impairment: the following abnormalities were found: 1) clinical
      (31.7%)-isolated tachycardia (1 case), congestive heart failure (12 cases). 2)
      electrocardiographic (43.9%)- sinus tachycardia associated with other
      abnormalities (10 cases), incomplete right bundle branch block (5 cases), left
      anterior hemiblock (1 case), right anterior hemiblock (1 case), changes in
      ventricular repolarization (11 cases), right ventricular overload (2 cases), left
      ventricular overload (1 case), right QRS axis deviation (1 case), and arrhythmias
      (3 cases). 3) echocardiographic (26.8%)- dilated cardiomyopathy (5 cases),
      pericardial effusion with tamponade (2 cases), pulmonary hypertension (2 cases),
      and mitral valve prolapse (1 case). CONCLUSION: Cardiac involvement was a
      characteristic of the HIV-infected group. Higher prevalence of abnormalities was
      found among children belonging to the most advanced clinical and immunological
      category. The most commonly observed clinical, electrocardiographic and
      echocardiographic findings were congestive heart failure (CHF), changes in
      ventricular repolarization, and dilated cardiomyopathy, respectively. The latter
      was reversible in one case. Electrocardiogram changes were significantly more
      frequent than clinical and echocardiographic changes.

PMID- 16283029
TI  - [Erectile dysfunction: a marker for myocardial perfusion impairment?].
AB  - OBJECTIVE: To study the correlation between erectile dysfunction (ED) and
      myocardial perfusion impairment in men with suspected or diagnosed coronary
      artery disease (CAD). METHODS: In this prospective study a self-administered IIEF
      5 questionnaire was answered by 287 patients that underwent myocardial perfusion
      imaging under both resting and stress condition with technetium-99m sestamibi,
      through gated SPECT nuclear scintigraphy technique, before and after physical or
      pharmacological stress. RESULTS: Some degree of erectile dysfunction (group ED+)
      was found in 137 (47.8%) patients and in these, age was significantly higher
      (60.60+/-9.84 vs 50.67+/-9.94 - p<0.001)) than in those without erectile
      dysfunction (group ED-). In the ED+ group, it was observed a higher prevalence of
      hypertension, diabetes, myocardial infarction (MI) and percutaneous coronary
      angioplasty (PCTA). Regardless of the age factor, ED+ patients also presented
      higher occurrence of myocardial perfusion impairment (necrosis and/or ischemia)
      and left ventricular systolic wall motion and thickening abnormalities.
      CONCLUSION: Patients with ED have higher estimated probability of presenting
      segmental myocardial perfusion and functional contraction impairment and,
      therefore, CAD, independent of the aging factor. The authors conclude that ED may
      be considered not only a marker for CAD but also a condition related to the
      occurrence of major coronary events such as MI and PCTA.

PMID- 16283030
TI  - [Therapy of advanced heart failure adapted to hemodynamic objectives acquired by
      invasive hemodynamic monitoring].
AB  - OBJECTIVE: To assess advanced heart failure (HF) treatment in relation to
      reduction of ventricular filling pressures, with the use of greater doses of
      vasodilators, through invasive hemodynamic monitoring. METHODS: Nineteen advanced
      HF patients were studied, in whom Swan-Ganz catheter was inserted to direct
      administration of diuretic intravenously (IV) and sodium nitroprusside, with the
      aim of significantly reduce ventricular filling pressures. After achieving such
      objective or 48 hours, oral drugs were introduced until venous medicines were
      removed, keeping hemodynamic benefit. RESULTS: From 19 patients studied, 16 (84%)
      were of male sex. The average age was 66 +/- 11.4 years old; average ejection
      fraction was 26 +/- 6.3%; 2 patients (10.5%) showed functional class (FC) III and
      17 (89.5%), FC IV. There was a decrease of pulmonary artery occlusion pressure
      from 23 +/- 11.50 mmHg to 16 +/- 4.05 mmHg (p = 0.008), of systemic vascular
      resistance index from 3,023 +/- 1,153.71 dynes/s/cm-5/m(2) to 1,834 +/- 719.34
      dynes/s/cm-5/m(2) (p = 0.0001) and an increase of cardiac index from 2.1 +/- 0.56
      l/min/m(2) to 2.8 +/- 0.73 l/min/m(2) (p = 0.0003). A subgroup with hypovolemia
      was identified. CONCLUSION: It was possible to reduce ventricular filling
      pressures to significantly lower values, obtaining a significant improvement of
      cardiac index, systemic vascular resistance index and pulmonary artery mean
      pressure, by using significantly higher doses of vasodilators.

PMID- 16283031
TI  - [Prospective risk analysis in patients submitted to myocardial revascularization
      surgery].
AB  - OBJECTIVE: To perform a stratified risk analysis in Myocardial Revascularization
      Surgery (MRS). METHODS: 814 patients were prospectively studied by applying two
      prognostic indexes (PI): Parsonnet and Modified Higgins. The Higgins PI was
      modified by substituting the variable "cardiac index value" by "low cardiac
      output syndrome" at the Intensive Care Unit (ICU) admission. The discriminatory
      capacity for morbimortality of both indexes was analyzed by ROC (receiver
      operating characteristic) curve. Logistic reaction identified the associated
      factors, independently from the events. RESULTS: Mortality and morbidity rates
      were 5.9% and 35.5%, respectively. The Modified Higgins PI, which analyzes pre-
      and intra-operative and physiological variables at the ICU admission showed areas
      under the ROC curve of 77% for mortality and 67% for morbidity. The Parsonnet PI,
      which only analyzes pre-operative variables, showed areas of 62.2% and 62.4%,
      respectively. Twelve variables were characterized as independent prognostic
      factors: age, diabetes mellitus, low body surface, creatinine levels (>1.5
      mg/dL), hypoalbuminemia, non-elective surgery, prolonged time of extracorporeal
      circulation (ECC), necessity of post-ECC intra-aortic balloon, low cardiac output
      syndrome at the ICU admission, elevated cardiac frequency, decrease in serum
      bicarbonate concentrations and increase of the alveolar-arterial oxygen gradient
      within this period. CONCLUSION: The Modified Higgins PI showed to be superior to
      the Parsonnet PI at the surgical risk stratification, showing the importance of
      the analysis of intraoperative events and physiological variables at the
      patient's ICU admission, when prognostic definition is achieved.

PMID- 16283032
TI  - [Prognostic factors of survival in post-cardiopulmonary-cerebral resuscitation in
      general hospital].
AB  - OBJECTIVE: To assess clinical and demographic characteristics of patients who had
      cardiopulmonary resuscitation and identify short- and long-term survival
      prognostic factors. METHODS: Four hundred and fifty-two (452) resuscitated
      patients in general hospitals from Salvador were prospectively assessed through
      bivariate and stratified analysis in associations between variables and survival
      curve for a nine-year evolution assessment. RESULTS: Age ranged from 14 to 93
      years old, mean of 54.11 years old. Male gender patients prevailed and half of
      them had at least a base disease. Cardiovascular disease was the responsible
      etiology in 50% of cases. Cardiac arrest was observed in 77% of cases and only
      69% of patients were immediately resuscitated. Initial cardiac rhythm was not
      diagnosed in 59% of patients. Asystole was the most frequent rhythm (42%),
      followed by ventricular arrhythmia (35%). Immediate survival was 24% and hospital
      discharge survival 5%. Cardiac arrest etiology, initial cardiac rhythm diagnosis,
      ventricular fibrillation or tachycardia as arrest mechanism, pre-resuscitation
      estimated time lower than or equal to 15 minutes and resuscitation time lower
      than or equal to 5 minutes were recognized as short-term prognostic factors. Non
      administration of epinephrine, being resuscitated in private hospital and
      resuscitation time lower than or equal to 15 minutes were nine-year evolution
      survival prognostic factors. CONCLUSION: Data may help healthcare professionals
      decide when start or stop in-hospital resuscitation.

PMID- 16283033
TI  - [State of the art of percutaneous procedure: octogenarian patient successfully
      submitted, in a single session, to a pulmonary valvotomy, coronary stent
      implantation and permanent pacemaker implantation].
AB  - This report describes a case involving an 82 year old patient with mild renal
      insufficiency, severe pulmonary valve stenosis (PVS), severe anterior descending
      artery stenosis and complete atrioventricular block, who successfully underwent,
      in a single session, coronary angioplasty and a stent implant, pulmonary
      valvotomy and a permanent pacemaker implant.

PMID- 16283034
TI  - [Biventricular endomyocardiofibrosis associated with renal amyloidosis].
AB  - Endomyocardiofibrosis is a restrictive cardiomyopathy characterized by fibrotic
      involvement of the endocardium and adjacent myocardium, and by diastolic
      dysfunction caused by changes in distensibility making ventricular filling
      inadequate while preserving the systolic function. Clinically, it appears as
      heart failure, but etiological symptomatic discernment, suspicion and a clinical
      examination would be necessary in order to make a correct etiological diagnosis.
      The case of a patient with biventricular endomyocardial fibrosis associated with
      renal amyloidosis is presented.

PMID- 16283036
TI  - [I forbid, therefore I assist].

PMID- 16283035
TI  - [Percutaneous management of penetrating aortic ulcer].
AB  - Penetrating aortic ulcer is a variant of classic aortic dissection having
      distinct histopathological characteristics. If not appropriately treated, it
      evolves to combined morbidity and mortality rates as high as those of classic
      dissection. This condition, therefore, warrants special attention with accurate
      diagnosis and treatment. Percutaneous management using endoprosthesis is the
      method of choice, since the patients are usually elderly and have comorbidities
      that would increase the complication rates of traditional surgery. A 78-year-old
      woman complaining of thoracic pain was admitted to the hospital; her pain had
      been radiating to the interscapular and left lumbar regions for four months. Upon
      diagnostic investigation, a penetrating aortic ulcer was found, and after being
      successfully treated percutaneously with stent implantation, the patient became
      asymptomatic and is under outpatient follow-up.

PMID- 16283037
TI  - [Myocardial revascularization without extracorporeal circulation].

PMID- 16283038
TI  - [Fat pulmonary embolism during orthopedic surgery monitored through
      transesophageal echocardiogram].

PMID- 16283039
TI  - [A 88 year-old man with acute pulmonary edema, cardiogenic shock and holosystolic
      murmur of recent onset].

PMID- 16283040
TI  - [Catheter ablation of atrial fibrillation: techniques and results].

PMID- 16283042
TI  - Health statistics: time to get serious.

PMID- 16283044
TI  - Global Fund withdraws grants to Myanmar.

PMID- 16283043
TI  - Knowledge translation in global health.

PMID- 16283045
TI  - Emerging diseases fuel health screening.

PMID- 16283046
TI  - "Learning to Fly" in a world of information overload.

PMID- 16283049
TI  - Analysis of how the health systems context shapes responses to the control of
      human immunodeficiency virus: case-studies from the Russian Federation.
AB  - OBJECTIVE: To develop a methodology and an instrument that allow the simultaneous
      rapid and systematic examination of the broad public health context, the health
      care systems, and the features of disease-specific programmes. METHODS: Drawing
      on methodologies used for rapid situational assessments of vertical programmes
      for tackling communicable disease, we analysed programmes for the control human
      of immunodeficiency virus (HIV) and their health systems context in three regions
      in the Russian Federation. The analysis was conducted in three phases: first,
      analysis of published literature, documents and routine data from the regions;
      second, interviews with key informants, and third, further data collection and
      analysis. Synthesis of findings through exploration of emergent themes, with
      iteration, resulted in the identification of the key systems issues that
      influenced programme delivery. FINDINGS: We observed a complex political economy
      within which efforts to control HIV sit, an intricate legal environment, and a
      high degree of decentralization of financing and operational responsibility.
      Although each region displays some commonalities arising from the Soviet
      traditions of public health control, there are considerable variations in the
      epidemiological trajectories, cultural responses, the political environment,
      financing, organization and service delivery, and the extent of multisectoral
      work in response to HIV epidemics. CONCLUSION: Within a centralized, post-Soviet
      health system, centrally directed measures to enhance HIV control may have
      varying degrees of impact at the regional level. Although the central tenets of
      effective vertical HIV programmes may be present, local imperatives substantially
      influence their interpretation, operationalization and effectiveness. Systematic
      analysis of the context within which vertical programmes are embedded is
      necessary to enhance understanding of how the relevant policies are prioritized
      and translated to action.

PMID- 16283051
TI  - Does scale matter? The costs of HIV-prevention interventions for commercial sex
      workers in India.
AB  - OBJECTIVE: To explore how the scale of a project affects both the total costs and
      average costs of HIV prevention in India. METHODS: Economic cost data and
      measures of scale (coverage and service volume indicators for number of cases of
      sexually transmitted infections (STIs) referred, number of STIs treated, condoms
      distributed and contacts made with target groups) were collected from 17
      interventions run by nongovernmental organizations aimed at commercial sex
      workers in southern India. Nonparametric methods and regression analyses were
      used to look at the relationship between total costs, unit costs and scale.
      FINDINGS: Coverage varied from 250 to 2008 sex workers. Annual costs ranged from
      US$ 11 274 to US$ 52 793. The median cost per sex worker reached was US$ 19.21
      (range = US$ 10.00-51.00). The scale variables explain more than 50% of the
      variation in unit costs for all of the unit cost measures except cost per
      contact. Total costs and unit costs have non-linear relationships to scale.
      CONCLUSION: Average costs vary with the scale of the project. Estimates of
      resource requirements based on a constant average cost could underestimate or
      overestimate total costs. The results highlight the importance of improving scale
      specific cost information for planning.

PMID- 16283050
TI  - Estimating the burden of shigellosis in Thailand: 36-month population-based
      surveillance study.
AB  - OBJECTIVE: To estimate incidence of shigellosis in the Kaengkhoi district,
      Saraburi Province, Thailand. METHODS: Population-based surveillance of
      shigellosis based in treatment centres. The detected rates of treated shigellosis
      were corrected for the number of cases missed due to the low sensitivity of
      microbiological culture methods and participants' use of health-care providers
      not participating in the study. FINDINGS: The overall uncorrected incidence of
      shigellosis was 0.6/1000 population per year (95% confidence interval (CI) = 0.5
      0.8). The unadjusted incidence of treated shigellosis was highest among children
      less than 5 years old (4/1000 children per year; 95% CI = 3-6) and significantly
      lower among people aged > 5 years (0.3/1000 population per year; 95% CI = 0.2
      0.5; P < 0.001). Adjusting for cases likely to be missed as a result of culture
      and surveillance methods increased estimates approximately five times. The
      majority of Shigella isolates (122/146; 84%) were S. sonnei; the rest were S.
      flexneri. Of the 22 S. flexneri isolates, the three most frequently encountered
      serotypes were 2a (36%), 1b (23%) and 3b (28%). A total of 90-95% of S. sonnei
      and S. flexneri isolates were resistant to tetracycline and co-trimoxazole. In
      contrast to S. sonnei isolates, more than 90% of the S. flexneri isolates were
      also resistant to ampicillin and chloramphenicol (P < 0.0001). CONCLUSION:
      Estimates of incidence of Shigella infection in the community are 10-fold to 100
      fold greater than those found from routine government surveillance. The high
      prevalence of Shigella strains resistant to multiple antibiotics adds urgency to
      the development of a vaccine to protect against shigellosis in this region of
      Thailand.

PMID- 16283052
TI  - Using lot quality-assurance sampling and area sampling to identify priority areas
      for trachoma control: Viet Nam.
AB  - OBJECTIVE: To report on the use of lot quality-assurance sampling (LQAS) surveys
      undertaken within an area-sampling framework to identify priority areas for
      intervention with trachoma control activities in Viet Nam. METHODS: The LQAS
      survey method for the rapid assessment of the prevalence of active trachoma was
      adapted for use in Viet Nam with the aim of classifying individual communes by
      the prevalence of active trachoma among children in primary school. School-based
      sampling was used; school sites to be sampled were selected using an area
      sampling approach. A total of 719 communes in 41 districts in 18 provinces were
      surveyed. FINDINGS: Survey staff found the LQAS survey method both simple and
      rapid to use after initial problems with area-sampling methods were identified
      and remedied. The method yielded a finer spatial resolution of prevalence than
      had been previously achieved in Viet Nam using semiquantitative rapid assessment
      surveys and multistage cluster-sampled surveys. CONCLUSION: When used with area
      sampling techniques, the LQAS survey method has the potential to form the basis
      of survey instruments that can be used to efficiently target resources for
      interventions against active trachoma. With additional work, such methods could
      provide a generally applicable tool for effective programme planning and for the
      certification of the elimination of trachoma as a blinding disease.

PMID- 16283053
TI  - The geographical distribution of underweight children in Africa.
AB  - OBJECTIVE: To study geographical patterns of underweight children in Africa by
      combining information on prevalence with headcounts at a subnational level.
      METHODS: We used large-scale, nationally representative nutrition surveys, in
      particular the Demographic and Health Surveys and the Multiple Indicator Cluster
      Surveys, which have been designed, analysed and presented according to largely
      similar protocols, and which report at the national and subnational levels.
      FINDINGS: We found distinct geographical patterns in the occurrence of
      underweight children, which could be linked to factors such as agronomic and
      climatic conditions, population density and economic integration. CONCLUSION:
      Patterns of underweight children cross national borders suggesting that regional
      characteristics and interactions need to be considered when addressing
      malnutrition.

PMID- 16283054
TI  - Dual job holding by public sector health professionals in highly resource
      constrained settings: problem or solution?
AB  - This paper examines the policy options for the regulation of dual job holding by
      medical professionals in highly resource-constrained settings. Such activity is
      generally driven by a lack of resources in the public sector and low pay, and has
      been associated with the unauthorized use of public resources and corruption. It
      is also typically poorly regulated; regulations are either lacking, or when they
      exist, are vague or poorly implemented because of low regulatory capacity. This
      paper draws on the limited evidence available on this topic to assess a number of
      regulatory options in relation to the objectives of quality of care and access to
      services, as well as some of the policy constraints that can undermine
      implementation in resource-poor settings. The approach taken in highlighting
      these broader social objectives seeks to avoid the value judgements regarding
      dual working and some of its associated forms of behaviour that have tended to
      characterize previous analyses. Dual practice is viewed as a possible system
      solution to issues such as limited public sector resources (and incomes), low
      regulatory capacity and the interplay between market forces and human resources.
      This paper therefore offers some support for policies that allow for the official
      recognition of such activity and embrace a degree of professional self
      regulation. In providing clearer policy guidance, future research in this area
      needs to adopt a more evaluative approach than that which has been used to date.

PMID- 16283055
TI  - Investing in children's health: what are the economic benefits?
AB  - This paper argues that investing in children's health is a sound economic
      decision for governments to take, even if the moral justifications for such
      programmes are not considered. The paper also outlines dimensions that are often
      neglected when public investment decisions are taken. The conclusion that can be
      drawn from the literature studying the relationship between children's health and
      the economy is that children's health is a potentially valuable economic
      investment. The literature shows that making greater investments in children's
      health results in better educated and more productive adults, sets in motion
      favourable demographic changes, and shows that safeguarding health during
      childhood is more important than at any other age because poor health during
      children's early years is likely to permanently impair them over the course of
      their life. In addition, the literature confirms that more attention should be
      paid to poor health as a mechanism for the intergenerational transmission of
      poverty. Children born into poor families have poorer health as children, receive
      lower investments in human capital, and have poorer health as adults. As a
      result, they will earn lower wages as adults, which will affect the next
      generation of children who will thus be born into poorer families.

PMID- 16283056
TI  - Mycobacterium ulcerans disease.
AB  - Mycobacterium ulcerans disease (Buruli ulcer) is an important health problem in
      several west African countries. It is prevalent in scattered foci around the
      world, predominantly in riverine areas with a humid, hot climate. We review the
      epidemiology, bacteriology, transmission, immunology, pathology, diagnosis and
      treatment of infections. M. ulcerans is an ubiquitous micro-organism and is
      harboured by fish, snails, and water insects. The mode of transmission is
      unknown. Lesions are most common on exposed parts of the body, particularly on
      the limbs. Spontaneous healing may occur. Many patients in endemic areas present
      late with advanced, severe lesions. BCG vaccination yields a limited, relatively
      short-lived, immune protection. Recommended treatment consists of surgical
      debridement, followed by skin grafting if necessary. Many patients have
      functional limitations after healing. Better understanding of disease
      transmission and pathogenesis is needed for improved control and prevention of
      Buruli ulcer.

PMID- 16283057
TI  - Association or causation: evaluating links between "environment and disease".

PMID- 16283059
TI  - The first reports on smoking and lung cancer: why are they consistently ignored?

PMID- 16283060
TI  - Bring tobacco and alcohol control to the fore to achieve the health MDGs.

PMID- 16283062
TI  - Exercise frequency and calcium intake predict 4-year bone changes in
      postmenopausal women.
AB  - The aim of this study was to examine the association of exercise frequency and
      calcium intake (CI) with change in regional and total bone mineral density (BMD)
      in a group of postmenopausal women completing 4 years of progressive strength
      training. One hundred sixty-seven calcium-supplemented (800 mg/day) sedentary
      women (56.1+/-4.5 years) randomized to a progressive strength training exercise
      program or to control were followed for 4 years. Fifty-four percent of the women
      were using hormone therapy (HT) at baseline. At 1 year, controls were permitted
      to begin the exercise program (crossovers). The final sample included 23
      controls, 55 crossovers, and 89 randomized exercisers. Exercisers were instructed
      to complete two sets of six to eight repetitions of exercises at 70-80% of one
      repetition maximum, three times weekly. BMD was measured at baseline and
      thereafter annually using dual-energy X-ray absorptiometry. Four-year percentage
      exercise frequency (ExFreq) averaged 26.8%+/-20.1% for crossovers (including the
      first year at 0%), and 50.4%+/-26.7% for exercisers. Four-year total CI averaged
      1,635+/-367 mg/day and supplemental calcium intake, 711+/-174 mg/day. In adjusted
      multiple linear regression models, ExFreq was positively and significantly
      related to changes in femur trochanter (FT) and neck (FN), lumbar spine (LS), and
      total body (TB) BMD. Among HT users, FT BMD increased 1.5%, and FN and LS BMD,
      1.2% (p<0.01) for each standard deviation (SD) of percentage ExFreq (29.5% or 0.9
      days/week). HT non-users gained 1.9% and 2.3% BMD at FT and FN, respectively,
      (p<0.05) for every SD of CI. The significant, positive, association between BMD
      change and ExFreq supports the long-term usefulness of strength training exercise
      for the prevention of osteoporosis in postmenopausal women, especially HT users.
      The positive relationship of CI to change in BMD among postmenopausal women not
      using HT has clinical implications in light of recent evidence of an increased
      health risk associated with HT.

PMID- 16283063
TI  - Trend in hip fracture epidemiology over a 14-year period in a Spanish population.
AB  - Spain lacks detailed data on hip fracture trends despite being the country with
      the greatest increase in the pensioner-to-provider ratio in Europe. We reproduced
      a study on hip fracture incidence in a region of northern Spain (Cantabria)
      carried out 14 years ago to determine whether a secular trend to change is taking
      place. If such a trend could be found, our objective was to determine whether the
      effect is solely due to ageing or whether additional variables are involved. We
      assessed the incidence of hip fracture in patients aged > or =50 years through
      clinical records from Emergency Units and Orthopedic Surgical Units of all
      hospitals in the region of Cantabria in 1988 and 2002. A total of 318 new cases
      of hip fracture were recorded in 1988 and 490 in 2002 (54% increase; p<0.001). No
      significant changes were noticed following an adjustment for age. Women accounted
      for the increase in crude hip fracture incidence [246 women and 72 men suffered a
      hip fracture in 1988 compared to 404 women and 86 men in 2002 (64% increase in
      women and 19% increase in men; p<0.005 and not significant, respectively)]. The
      female:male ratio was 3.4 in 1988 versus 4.7 in 2002; following age-adjustment,
      no significant changes were found (1.8 in 1988 and 1.9 in 2002). The increase in
      crude hip fracture incidence was greater at cervical (versus trochanteric) sites.
      Patient residence, time of the year, site of fracture, kind of injury, previous
      contralateral hip fracture, length of stay, and peri-operative mortality did not
      differ significantly. In conclusion, a crude hip fracture incidence increase of
      about 50% in the northern Spanish region of Cantabria has taken place over the
      last 14 years. This effect does not persist after adjustments have been made for
      age. The crude rate increase occurred mainly at the expense of women, with a more
      noticeable rise in cervical fractures as opposed to trochanteric lesions.

PMID- 16283064
TI  - Costs and quality of life associated with osteoporosis-related fractures in
      Sweden.
AB  - This prospective observational data collection study assessed the cost and
      quality of life related to hip, vertebral and wrist fracture 1 year after the
      fracture, based on a patient sample consisting of 635 male and female patients
      surviving a year after fracture. Data regarding resource use and quality of life
      related to fractures was collected by questionnaires at baseline, 4 months and 12
      months. Information was collected by the use of patients' records, register
      sources and by asking the patient. Quality of life was estimated with the EQ-5D
      questionnaire. Costs were estimated from a societal perspective, including direct
      and indirect costs. The mean fracture-related cost the year after a hip,
      vertebral and wrist fracture were estimated, in euros (<euro>), at <euro>14,221,
      <euro>12,544 and <euro>2,147, respectively [converted from Swedish krona (SEK) at
      an exchange rate of 9.1268 SEK/<euro>]. The mean reduction in quality of life was
      estimated at 0.17, 0.26 and 0.06 for hip, vertebral and wrist fracture,
      respectively. Based on the results, the yearly burden of osteoporosis in Sweden
      could be estimated at <euro>0.5 billion (SEK 4.6 billion). The patient sample for
      vertebral fracture was fairly small and included a high proportion of fractures
      leading to hospitalization, but they indicate a higher cost and loss of quality
      of life related to vertebral fracture than previously perceived.

PMID- 16283065
TI  - Diabetes mellitus and the risk of non-vertebral fractures: the Tromso study.
AB  - We wanted to determine the risk of non-vertebral fracture associated with type
      and duration of diabetes mellitus, adjusting for other known risk factors. This
      is a population-based 6-year follow-up of 27,159 subjects from the municipality
      of Tromso, followed from 1994 until 2001. The age range was 25-98 years. Self
      reported diabetes cases were validated by review of the medical records. All non
      vertebral fractures were registered by computerized search in radiographic
      archives. A total of 1,249 non-vertebral fractures was registered, and 455
      validated cases of diabetes were identified. Men with type I diabetes had an
      increased risk of all non-vertebral [relative risk (RR) 3.1 (95% CI 1.3-7.4)] and
      hip fractures [RR 17.8 (95% CI 5.6-56.8)]. Diabetic women, regardless of type of
      diabetes, had significantly increased hip fracture risk [RR 8.9 (95% CI 1.2-64.4)
      and RR 2.0 (95% CI 1.2-3.6)] for type I and type II diabetes, respectively.
      Diabetic men and women using insulin had increased hip fracture risk. Duration of
      disease did not alter hip fracture risk. An increased risk of all non-vertebral
      fractures and, especially, hip fractures was associated with diabetes mellitus,
      especially type I. Type II diabetes was associated with increased hip fracture
      risk in women only.

PMID- 16283066
TI  - Osteoporosis intervention in ambulatory patients with previous hip fracture: a
      multicentric, nationwide Italian survey.
AB  - Our study investigated the patterns of treatment and adherence to prescribed
      therapies in 2,191 ambulatory patients with previous hip osteoporotic fractures
      at 207 participating orthopedic centers throughout Italy. All patients who came
      to the attention of the involved orthopedic surgeons were administered a
      questionnaire investigating: age, sex, height, weight, date of admission and
      length of stay in the hospital, other previous clinical fractures, bone density
      or biochemical testing concerning mineral metabolism, treatment with bone-active
      drugs in the six months before the fracture, treatment after discharge from the
      hospital, continuous use of prescribed drugs, pain at the site of hip surgery,
      and comorbidity. A multivariate logistic regression model was applied,
      considering a subset of the variables in the questionnaire, in order to determine
      the factors that significantly influenced discontinuation of treatment after hip
      fracture. Among the patients, 88.1% were female and 86.2% of the subjects were
      older than 65. The mean length of hospital stay for hip fracture was 19.0+/-25.3
      days. At the time of interview, the mean time elapsed since hospitalization was
      542.9+/-1,197.3 days. A previous clinical fracture was referred by 20.2% of
      patients. Before hip fracture occurrence, 52.8% of patients had never received
      any kind of treatment, and this figure reached 80% if we also included those who
      had taken only calcium and/or vitamin D. Corresponding proportions after fracture
      were 22% and 31.3%, respectively. Finally, 52% of patients had stopped treatment
      given for osteoporosis after a mean period of 1.4 years. According to the results
      of the logistic regression, increasing age, pain [odds ratio (OR): 1.36; 95%
      confidence interval (CI): 1.21-1.65] and no use of diagnostic tests (OR: 2.46;
      CI: 1.79-3.37) showed a positive effect on the probability of quitting the
      medication. On the other hand, being female reduces by half (OR: 0.49; CI: 0.37
      0.45) the probability of quitting medication. Our data showed a low rate of
      primary prevention, a still insufficient post-fracture therapy, along with a high
      rate of early discontinuation of osteoporosis medication in patients with
      previous hip fracture.

PMID- 16283067
TI  - Characteristics of elderly patients admitted to an urban tertiary care hospital
      with osteoporotic fractures: correlations with risk factors, fracture type,
      gender and ethnicity.
AB  - Osteoporosis is a major public health problem in the United States of America and
      around the world, largely due to the morbidity and mortality associated with
      osteoporotic fractures. In the past decade, large epidemiologic studies have
      contributed greatly to our understanding of patients who fracture. However, most
      studies are limited to postmenopausal white women. In this retrospective review,
      we analyze data from 185 men and women with acute fragility fractures who
      received osteoporosis consultations during admission to a single urban hospital
      between 2001 and 2003. Men and women differed in terms of risk factors for falls
      and osteoporosis but had areal bone mineral density (BMD) measurements remarkably
      similar, except at the total hip. Black and Hispanic subjects with fractures were
      significantly younger than whites yet were much more likely to have serious co
      morbidities, such as diabetes mellitus and hypertension. In spite of
      significantly higher BMD measurements, black patients had the highest rates of
      vitamin D deficiency and secondary hyperparathyroidism. Patients admitted with
      hip fractures differed from those with non-hip fractures on a number of important
      variables. Based on these data, we conclude that elderly subjects admitted to an
      urban hospital with osteoporotic fractures are a heterogeneous group, with
      features that vary according to fracture type, gender and ethnicity. Future
      studies of patients with clinical fragility fractures should include ample
      numbers of men and ethnic minorities, since differences in underlying risk
      factors may suggest alternative strategies for fracture prevention.

PMID- 16283068
TI  - Cystic fibrosis with homozygous R553X mutation in a Taiwanese child.
AB  - It has been reported that cystic fibrosis is very rare in Asians, and its
      clinical expression and genetic mutations are different from those found in
      Caucasians. We report the case of a boy who had chronic diarrhea with failure to
      thrive and frequent respiratory tract infections beginning at the age of 2
      months. He developed bronchiectasis with chronic severe hypoxemia and pancreatic
      insufficiency by the age of 3 years and 5 months, which raised the consideration
      of cystic fibrosis. DNA analysis revealed a homozygous R553X mutation, and both
      his parents were subsequently proven to be R553X carriers. This case is the first
      report in a Taiwanese with cystic fibrosis attributable to a mutation commonly
      seen in Caucasians. However, the age of onset was much younger and the clinical
      course was more severe than those associated with Western patients. We reviewed
      the eight reported Taiwanese patients with cystic fibrosis, including the present
      case. We believe that the incidence of cystic fibrosis in Taiwan may be
      underestimated. Both genetic and environmental factors may play a role in the
      phenotypic disparity between Asians and Caucasians.

PMID- 16283070
TI  - Selfing and inbreeding depression in seeds and seedlings of Neobalanocarpus
      heimii (Dipterocarpaceae).
AB  - We evaluated the degree of selfing and inbreeding depression at the seed and
      seedling stages of a threatened tropical canopy tree, Neobalanocarpus heimii,
      using microsatellite markers. Selection resulted in an overall decrease in the
      level of surviving selfed progeny from seeds to established seedlings, indicating
      inbreeding depression during seedling establishment. Mean seed mass of selfed
      progeny was lower than that of outcrossed progeny. Since the smaller seeds
      suffered a fitness disadvantage at germination in N. heimii, the reduced seed
      mass of selfed progeny would be one of the determinants of the observed
      inbreeding depression during seedling establishment. High selfing rates in some
      mother trees could be attributed to low local densities of reproductive
      individuals, thus maintenance of a sufficiently high density of mature N. heimii
      should facilitate regeneration and conservation of the species.

PMID- 16283069
TI  - Magnetoreception in plants.
AB  - This article reviews phenomena of magnetoreception in plants and provides a
      survey of the relevant literature over the past 80 years. Plants react in a
      multitude of ways to geomagnetic fields-strong continuous fields as well as
      alternating magnetic fields. In the past, physiological investigations were
      pursued in a somewhat unsystematic manner and no biological advantage of any
      magnetoresponse is immediately obvious. As a result, most studies remain largely
      on a phenomenological level and are in general characterised by a lack of
      mechanistic insight, despite the fact that physics provides several theories that
      serve as paradigms for magnetoreception. Beside ferrimagnetism, which is well
      proved for bacterial magnetotaxis and for some cases of animal navigation, two
      further mechanisms for magnetoreception are currently receiving major attention:
      (1) the "radical-pair mechanism" consisting of the modulation of singlet-triplet
      interconversion rates of a radical pair by weak magnetic fields, and (2) the "ion
      cyclotron resonance" mechanism. The latter mechanism centres around the fact that
      ions should circulate in a plane perpendicular to an external magnetic field with
      their Lamor frequencies, which can interfere with an alternating electromagnetic
      field. Both mechanisms provide a theoretical framework for future model-guided
      investigations in the realm of plant magnetoreception.

PMID- 16283072
TI  - Spermatic cord liposarcoma: a diagnostic challenge.
AB  - Spermatic cord liposarcoma (SCL) is a rare medical condition; to our knowledge
      there have been fewer than 100 cases reported in the literature worldwide. As a
      group, para-testicular tumors are relatively uncommon, and they must be
      differentiated from tumors of testicular origin with extension to the spermatic
      cord and its elements. SCL should be suspected in patients experiencing recurrent
      hernias of the inguinal region. Herein we present two cases of SCL recently
      diagnosed at our hospital. In both instances, the preoperative diagnosis was
      inguinal hernia.

PMID- 16283071
TI  - Transcriptional coactivator MBF1s from Arabidopsis predominantly localize in
      nucleolus.
AB  - Multiprotein bridging factor 1 (MBF1) is a transcriptional coactivator. It has
      been reported that MBF1 changed its subcellular localization from cytoplasm into
      nuclei with a transcriptional activator for activation of a target gene
      expression in animals. We found that Arabidopsis MBF1s (AtMBF1s) predominantly
      localize in nucleolus. We previously reported that plant MBF1s were rapidly
      induced by several stresses, whereas animal MBF1s were not induced. Therefore, we
      suggest that MBF1-function in plants is controlled on the level of
      transcriptional induction but not by nuclear translocation, dissimilar from the
      case of MBF1s from animals.

PMID- 16283073
TI  - Femoral hernia: a review of 83 cases.
AB  - We evaluate the factors that affect morbidity and mortality in patients who
      underwent surgery due to femoral hernia. The medical records of 83 patients who
      underwent femoral hernia repair between January 1996 and June 2004 were
      retrospectively analyzed. The femoral hernias were repaired either with McVay or
      mesh plug hernioplasty. Sex, age, surgical repair technique, presence of
      incarceration/strangulation, incarcerated/strangulated organs, postoperative
      complications, duration of hospitalization, recurrence rate, and factors that
      affect mortality and morbidity were studied. There were 83 patients with femoral
      hernia in our study. Patients' age ranged from 10 to 75 years (mean age was
      46.84) with a predominance of female (71%). Thirty-six patients (40%) underwent
      emergency surgery with the diagnosis of strangulation or incarceration of femoral
      hernia. Seventeen patients had strangulation and underwent resection; eleven of
      these patients had omentum in the hernial sac, whereas six patients had
      intestines. Four of these patients underwent laparotomy. The remaining 19
      patients had incarceration and underwent simple reduction of hernial sac content
      without resection. Forty-seven (60%) patients underwent elective surgery. McVay
      technique was used for 79 patients, while the other four patients were treated
      with mesh-plug. Twelve patients (15%) developed a variety of complications (nine
      patients (25%) in emergency, three patients (6%) in elective group). There was
      one mortality. Recurrences occurred in two patients. Femoral hernia is an
      important surgical pathology with high rates of incarceration/strangulation and
      intestinal resection. Emergency surgery can increase morbidity and mortality
      especially in the elderly. Early elective surgery may reduce complication.

PMID- 16283074
TI  - Incisional pubic hernia: treatment of a case with congenital malformation of the
      pelvis.
AB  - Parapubic hernia is a rare entity, the aetiology of which is usually associated
      with pelvic surgery, traumatisms and bone malformations. Treatment is difficult
      because the defect is usually limited by altered fibrotic anatomical planes. We
      present a case of incisional pubic hernia in a patient with congenital bladder
      exstrophy and multiple surgeries for pelvic reconstruction, who was treated using
      a plasty combined with a double intra-abdominal/supra-aponeurotic mesh. The
      therapeutic possibilities are described for the laparoscopic and open approaches
      in the management of these complex hernias.

PMID- 16283075
TI  - Experience with management of anterior abdominal wall defects using bovine
      pericard.
AB  - During 5 years from 1999 until 2003, our experience with 29 (100%) neonates
      managed for anterior abdominal wall defects is presented. Twenty-one (72%)
      neonates presented with gastroschisis and 8 (28%) neonates with giant
      omphaloceles. The male:female ratio was almost equal in gastroschisis (1:1) while
      a male predominance was observed in omphaloceles (6:1). A primary closure of the
      defect was possible in 5 (17%) cases and a single patch along with skin closure
      was achieved in a further 9 (31%) cases. In 15 (52%) neonates the defect was
      large and two patches were employed to sufficiently cover the defect. All
      patients (97%), except one (mortality due to extreme prematurity), were managed
      successfully. Depending upon the size of the defect and the metabolic condition
      of the neonate, the defect closure was completed after a mean of 85.7 days.
      Special protocols were created to manage the bovine pericard patches, which
      behaved differently to lyophilized dura patches previously used at our center.
      Integration of the patches was successful in 28 (97%) neonates; however, one
      neonate with gastroschisis presented significant challenges in the management.
      Bovine pericard patches are optimal biomaterials for the closure of anterior
      abdominal wall defects in gastroschisis and omphaloceles.

PMID- 16283077
TI  - Comments on the misuse of terminology in savant research: it is not the sieve of
      Eratosthenes.

PMID- 16283076
TI  - Cor triatriatum dexter in two adult patients.
AB  - Cor triatriatum dexter, in which the right atrium (RA) is divided into two
      chambers by a membrane, is a very rare congenital abnormality. In this
      abnormality, there is a high incidence of associated congenital abnormalities,
      particularly of the right heart. We presented two men with cor triatriatum
      dexter. Echocardiography is discussed as a non-invasive diagnostic tool.

PMID- 16283078
TI  - Childhood Disintegrative Disorder, an atypical presentation: a case report.

PMID- 16283079
TI  - Lumpers, splitters, and Asperger syndrome.

PMID- 16283080
TI  - Brief report: relations between prosodic performance and communication and
      socialization ratings in high functioning speakers with autism spectrum
      disorders.
AB  - Shriberg et al. [Shriberg, L. et al. (2001). Journal of Speech, Language and
      Hearing Research, 44, 1097-1115] described prosody-voice features of 30 high
      functioning speakers with autistic spectrum disorder (ASD) compared to age
      matched control speakers. The present study reports additional information on the
      speakers with ASD, including associations among prosody-voice variables and
      ratings of communication social abilities. Results suggest that the inappropriate
      sentential stress and hypernasality previously identified in some of these
      speakers is related to communication/sociability ratings. These findings and
      associated trends are interpreted to indicate important links between prosodic
      performance and social and communicative competence. They suggest the need for
      careful assessment of inappropriate prosody and voice features in speakers with
      ASD, and for effective intervention programs aimed at reducing the stigmatization
      of individuals with these conditions.

PMID- 16283081
TI  - Teaching children with autism when reward is delayed. The effects of two kinds of
      marking stimuli.
AB  - Three children with autism were taught to identify pictures of emotions in
      response to their spoken names. Their speed of acquisition was compared using a
      within-child alternating treatments design across three teaching conditions, each
      involving a 5 second delay to reinforcement. In the marked-before condition, an
      instruction encouraged the children to visually orient to the cards before they
      made their choice response; in the marked-after condition, an attention-eliciting
      verbal cue (e.g., "Look!") was delivered after both correct and incorrect
      responses; in the delay condition, these marking cues were omitted. Performance
      in the no-cue control was inferior to both the marked-before and marked-after
      conditions, but the difference between the latter two conditions was not
      significant.

PMID- 16283082
TI  - Dysbindin (DTNBP1, 6p22.3) is associated with childhood-onset psychosis and
      endophenotypes measured by the Premorbid Adjustment Scale (PAS).
AB  - Straub et al. (2002) recently identified the 6p22.3 gene dysbindin (DTNBP1)
      through positional cloning as a schizophrenia susceptibility gene. We studied a
      rare cohort of 102 children with onset of psychosis before age 13. Standardized
      ratings of early development, medication response, neuropsychological and
      cognitive performance, premorbid dysfunction and clinical follow-up were
      obtained. Fourteen SNPs were genotyped in the gene DTNBP1. Family-based pairwise
      and haplotype transmission disequilibrium test (TDT) analysis with the clinical
      phenotype, and quantitative transmission disequilibrium test (QTDT) explored
      endophenotype relationships. One SNP was associated with diagnosis (TDT p=.01).
      The QTDT analyses showed several significant relationships. Four adjacent SNPs
      were associated (p values=.0009-.003) with poor premorbid functioning. These
      findings support the hypothesis that this and other schizophrenia susceptibility
      genes contribute to early neurodevelopmental impairment.

PMID- 16283083
TI  - Pre-linguistic Autism Diagnostic Observation Schedule adapted for older
      individuals with severe to profound mental retardation: a pilot study.
AB  - The Autism Diagnostic Observational Schedule (ADOS) is a semi-structured
      observational scale developed to assess social interaction, communication and
      play in individuals who are suspected to have autism. Since the ADOS is not
      suitable to be used with severely or profoundly mentally retarded adolescents and
      adults with very limited language skills, materials and some of the tasks of the
      PL-ADOS and the original ADOS (the former versions of the current ADOS) were
      adapted. Results indicated that almost all of the overall ratings showed good
      reliability and discriminative diagnostic validity. Furthermore, the combination
      of codings into an overall algorithm score on social/communicative behavior
      resulted in a sensitivity of .82 and a specificity of .85 when using a cut-off
      score of 15.

PMID- 16283084
TI  - An evaluation of the Gilliam Autism Rating Scale.
AB  - The Gilliam Autism Rating Scale was developed to identify individuals with autism
      in research and clinical settings. It has benefited from wide use and acceptance
      but has received little empirical attention. The purpose of this study was to
      evaluate the construct and diagnostic validity, interrater reliability, and
      effects of participant characteristics of the GARS in a large and heterogeneous
      sample of children and adolescents with autism spectrum disorders. 360 parent and
      teacher ratings were submitted to factor analysis. A three-factor solution
      explaining 38% of the variance was obtained. Almost half of all items loaded on a
      Repetitive and Stereotyped Behavior factor. The Developmental Disturbance
      subscale did not contribute to the Autism Quotient (AQ) and was poorly related to
      other subscales. Internal consistency for the three behavioral subscales was good
      but low for the Developmental Disturbance subscale. The average AQ was
      significantly lower than what was reported in the test manual, suggesting low
      sensitivity with the current cutoff criteria. Interrater reliability was also
      much lower than originally reported by the instrument's developer. No significant
      age or gender effects were found. Level of impairment, as measured by adaptive
      behavior, was negatively related to total and subscale scores. The implications
      of these findings were discussed, as was the use of diagnostic instruments in the
      field in general.

PMID- 16283085
TI  - Interval and contour processing in autism.
AB  - High functioning children with autism and age and intelligence matched controls
      participated in experiments testing perception of pitch intervals and musical
      contours. The finding from the interval study showed superior detection of pitch
      direction over small pitch distances in the autism group. On the test of contour
      discrimination no group differences emerged. These findings confirm earlier
      studies showing facilitated pitch processing and a preserved ability to represent
      small-scale musical structures in autism.

PMID- 16283086
TI  - Global-local precedence in the perception of facial age and emotional expression
      by children with autism and other developmental disabilities.
AB  - Global information processing and perception of facial age and emotional
      expression was studied in children with autism, language disorders, mental
      retardation, and a clinical control group. Children were given a global-local
      task and asked to recognize age and emotion in human and canine faces. Children
      with autism made fewer global responses and more errors when recognizing human
      and canine emotions and canine age than children without autism. Significant
      relationships were found between global information processing and the
      recognition of human and canine emotions and canine age. Results are discussed
      with respect to the relationship between global information processing and face
      perception and neural structures underlying these abilities.

PMID- 16283087
TI  - A training study of theory of mind and executive function in children with
      autistic spectrum disorders.
AB  - This study investigated the relationship between theory of mind and executive
      functioning in children with autistic spectrum disorders through a training
      study. Ten children were trained on theory of mind, whilst ten were trained in
      executive function. Seven children were assigned to a control group, receiving no
      intervention. Training programmes were administered individually, lasting for 25
      minutes per day for 5-10 days. Children were tested before training, after
      training and at a two-month follow-up. Significant improvements were seen in
      performance on theory of mind tasks in both trained groups, whilst the control
      group showed no improvement. No improvement on the executive function tasks was
      seen in any of the groups. The implications of these findings are discussed.

PMID- 16283090
TI  - (2,3,4,4-Tetramethylcyclopentyl)methyl acetate, a sex pheromone from the obscure
      mealybug: first example of a new structural class of monoterpenes.
AB  - The sex pheromone of the obscure mealybug, Pseudococcus viburni, consists of
      (1R*,2R*,3S*)-(2,3,4,4-tetramethylcyclopentyl)methyl acetate, the first example
      of a new monoterpenoid structural motif in which the two isoprene units forming
      the carbon skeleton are joined by 2'-2 and 3'-4 connections rather than the usual
      1'-4, head-to-tail connections. This highly irregular terpenoid structure, and
      the irregular terpenoid structures of related mealybug species, suggest that
      these insects may have unique terpenoid biosynthetic pathways.

PMID- 16283089
TI  - Structure factor scaling in colloidal charge heteroaggregation.
AB  - The structure factor, S(q), of a system composed of a 1:1 mixture of oppositely
      charged colloids undergoing heteroaggregation is studied by Browninan dynamics
      simulations. A peak develops in S(q) at low wave vectors, which can be scaled for
      different times to overlap using the scaling of spinodal decomposition, as shown
      for DLCA. The same master function is obtained for different interaction ranges.
      The origin of the peak can be traced back to a depletion layer of clusters
      surrounding every aggregate. At those long distances, cluster-cluster interaction
      is negligible and the aggregation is diffusion limitted, as deduced from the
      evolution of peak position, and the S(q) scaling at different interaction ranges.
      The interaction is, nevertheless, strong enough to affect the internal cluster
      structure.

PMID- 16283091
TI  - A blurring index for medical images.
AB  - This study was undertaken to investigate a useful image blurring index. This work
      is based on our previously developed method, the Moran peak ratio. Medical images
      are often deteriorated by noise or blurring. Image processing techniques are used
      to eliminate these two factors. The denoising process may improve image
      visibility with a trade-off of edge blurring and may introduce undesirable
      effects in an image. These effects also exist in images reconstructed using the
      lossy image compression technique. Blurring and degradation in image quality
      increases with an increase in the lossy image compression ratio. Objective image
      quality metrics [e.g., normalized mean square error (NMSE)] currently do not
      provide spatial information about image blurring. In this article, the Moran peak
      ratio is proposed for quantitative measurement of blurring in medical images. We
      show that the quantity of image blurring is dependent upon the ratio between the
      processed peak of Moran's Z histogram and the original image. The peak ratio of
      Moran's Z histogram can be used to quantify the degree of image blurring. This
      method produces better results than the standard gray level distribution
      deviation. The proposed method can also be used to discern blurriness in an image
      using different image compression algorithms.

PMID- 16283093
TI  - Comparing brain activation across groups with different motor abilities.

PMID- 16283094
TI  - Numb cheek syndrome as the first manifestation of anti-Hu paraneoplastic
      neuronopathy.

PMID- 16283095
TI  - Neurosarcoidosis. Clinical description of 7 cases with a proposal for a new
      diagnostic strategy.
AB  - OBJECTIVE: Chronic involvement of the nervous system is relatively rare in
      sarcoidosis. We describe 7 cases that fulfil Zajicek's criteria for
      neurosarcoidosis (NS) and propose some modifications to such criteria. MATERIALS
      AND METHODS: The patients were admitted for various neurological syndromes: 2
      cases presented with chronic lymphocytic meningitis, 4 with spinal cord symptoms,
      one case was initially confused with multiple sclerosis. Serological tests,
      immunological screening, cerebrospinal fluid (CSF) analysis, bacteriological and
      viral testing were performed in all patients. Spinal and cerebral MRI, gallium
      scan, bronchoscopy with biopsy and bronchoalveolar-lavage fluid analysis, high
      resolution computed tomography (HRCT) of the chest, biopsy of the lungs, skin,
      mediastinal lymph-node and meninges, were useful in diagnosing NS. RESULTS AND
      DISCUSSION: Laboratory tests showed serum inflammatory abnormalities, but were
      negative for infectious diseases, while CSF showed inflammatory signs in all
      patients. MRI revealed meningeal enhancement or hypertrophic pachymeningeal
      lesions in 4 patients, white matter abnormalities and mass lesions in 2 patients,
      and a spinal mass lesion in 1 patient. Gallium scan, HRCT, bronchoscopy were
      positive in most cases. Patients were treated with steroid and immunosuppressive
      therapy, with improvement in six cases. One patient died from infectious
      complications. CONCLUSION: A definite diagnosis of NS requires demonstration of
      non-caseating granulomas affecting nervous tissues. In most cases, histological
      evidence of systemic disease (probable NS) is sufficient in the presence of
      compatible alterations in the CNS. In our patients the bronchoalveolarlavage
      fluid analysis, gallium scan, and chest HRCT were important for diagnosis, while
      serum ACE was always normal and chest radiographs were not suggestive of
      sarcoidosis.

PMID- 16283096
TI  - Oxidative stress in serum and peripheral blood leukocytes in patients with
      different disease courses of multiple sclerosis.
AB  - BACKGROUND: The role of oxidative stress in patients with multiple sclerosis (MS)
      is poorly understood. OBJECTIVE: To investigate oxidative stress in serum and
      peripheral blood leukocytes in patients with different disease courses of MS.
      METHODS: Diene conjugate (DC) levels (a measure of lipid peroxidation), total
      antioxidative activity (AOA) and total antiradical activity (ARA) were measured
      in serum and peripheral blood leukocytes from 30 patients with benign relapsing
      remitting MS (BMS), 27 with secondary progressive MS (SPMS), 29 with primary
      progressive MS (PPMS), and 30 healthy controls. All MS patients were in a
      clinically stable phase. RESULTS: Serum DC levels were elevated in patients with
      BMS (p <0.05), SPMS (p <0.01) and PPMS (p <0.001). Serum total AOA and ARA were
      not different between MS patients and controls. Compared to controls, leukocyte
      DC levels were not different in each MS subgroup, but total ARA was elevated.
      There was a strong correlation, both in controls and MS patients, between
      leukocyte DC levels and leukocyte total ARA (p <0.0001) and leukocyte total AOA
      (p <0.0001). CONCLUSION: Oxidative stress occurs in progressive as well as benign
      MS. The finding that cells withstand oxidative stress, due to upregulated
      cellular antioxidant defence mechanisms, suggests that reactive oxygen species
      (ROS) formation in MS is not necessarily deleterious.

PMID- 16283097
TI  - Diabetes and cognitive impairment. Clinical diagnosis and brain imaging in
      patients attending a memory clinic.
AB  - BACKGROUND: Diabetes is a risk factor for dementia,but the issue whether this
      concerns only vascular dementia or also Alzheimer's disease is debated. We
      compared the clinical diagnoses and abnormalities on brain MRI in patients with
      or without diabetes who received standardised, detailed diagnostic studies at a
      memory clinic, in order to establish whether one specific type of dementia or
      specific MRI abnormalities were more common in diabetes. PATIENTS AND METHODS:
      Patients who visited our memory clinic between January 2002 and June 2004 were
      divided into a group with (n = 42) or without diabetes (n = 389). The diagnoses
      were recorded, and MRI scans were rated for (sub)cortical atrophy, medial
      temporal lobe atrophy, infarctions, and white matter changes. RESULTS: The
      proportion of Alzheimer's disease (36% versus 28%; OR 1.1 (95% CI 0.5-2.2),
      adjusted for age and sex), vascular dementia (5% versus 2%; OR 2.4 (0.5-12.1)),
      and so called "cognitive impairment no dementia" (24% versus 17%; 1.3 (0.6-2.9))
      was similar in patients with or without diabetes. On MRI lacunar and cortical
      infarctions were more common and cortical atrophy more pronounced among diabetic
      patients. By contrast, the severity of white matter changes was similar in the
      two groups. CONCLUSION: The relative frequency of different diagnoses among
      diabetic and non-diabetic patients attending a memory clinic was similar,
      indicating that diabetes does not predispose to one particular subtype of
      dementia. The imaging findings support the notion that the increased risk of
      cognitive decline and dementia in elderly subjects with diabetes is due to dual
      pathology, involving both cerebrovascular disease and cortical atrophy.

PMID- 16283098
TI  - Reproducibility of activation in four motor paradigms. An fMRI study.
AB  - Most functional imaging data are collected in single session experiments; little
      is known about the reproducibility or test-retest reliability of the activation
      patterns found in these experiments. In our study, 15 healthy volunteers
      performed four simple motor-paradigms ("Hand", "Foot", "Mouth" and "Tongue") for
      functional magnetic resonance imaging (fMRI) in 3 sessions on different days.
      Reproducibility of activations in four anatomical regions (pre- and postcentral
      gyri, paracentral lobule and the supplementary motor area) was measured in terms
      of voxels active in all sessions (common voxels) relative to voxels active in
      single sessions, giving reliability coefficients from 0 to 1. Two significance
      levels were used to identify active voxels. Reproducibility of activations was
      highest for foot and hand movements in the primary motorsensory areas;
      reliability coefficients were in the range of 0.62 to 0.78. Activations for mouth
      movements showed a very poor reproducibility. Application of the more stringent
      statistical threshold always led to a reduction of reproducible voxels.
      Reliability of fMRI data is not only a theoretical issue, but is of special
      practical importance in clinical settings such as integration of fMRI into
      neuronavigation for neurosurgical planning. Much care has to be taken if only
      single session data are available for interpretation.

PMID- 16283099
TI  - Neuropsychological function in relation to serum parathyroid hormone and serum 25
      hydroxyvitamin D levels. The Tromso study.
AB  - There are receptors for parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D in
      the brain, and there are clinical and experimental data indicating that PTH and
      vitamin D may affect cerebral function. In the present study 21 subjects who both
      in the 5th Tromso study and at a follow-up examination fulfilled criteria for
      secondary hyperparathyroidism (SHPT) without renal failure (serum calcium < 2.40
      mmol/L, serum PTH > 6.4 pmol/L, and normal serum creatinine) and 63 control
      subjects were compared with tests for cognitive and emotional function. Those in
      the SHPT group had significantly impaired performance in 3 of 14 cognitive tests
      (Digit span forward, Stroop test part 1 and 2, and Word association test (FAS))
      as compared with the controls, and also had a significantly higher depression
      score at the Beck Depression Inventory (BDI) (items 1-13). In a multiple linear
      regression model, a high serum PTH level was significantly associated with low
      performance at the Digit span forward, Stroop test part 1 and 2, and Digit Symbol
      tests. A low level of serum 25-hydroxyvitamin D was significantly associated with
      a high depression score. In conclusion, a deranged calcium metabolism appears to
      be associated with impaired function in several tests of neuropsychological
      function.

PMID- 16283100
TI  - Bickerstaff brainstem encephalitis after heat stroke.

PMID- 16283101
TI  - Diagnostic reference frames for seizures: A validation study.
AB  - INTRODUCTION: We developed structured descriptions of signs and symptoms for
      specific seizure types (called Diagnostic Reference Frames-DRFs-by us) that can
      serve as a frame of reference in the process of classifying patients with
      epileptic seizures. In this study the validity of the DRFs for clinical use is
      evaluated and described. MATERIAL AND METHODS: In this study we use a decision
      support system based on the DRFs and using Bayes's rule for the validation of the
      DRFs. Patient's manifestations are entered in the decision support system and by
      successively applying Bayes's rule posterior probabilities are calculated. The
      DRFs with the highest posterior probability gives an indication of the
      classification of the seizure. The validation of the DRFs was performed by
      comparing the seizure type with the highest posterior probability with the
      classification of experienced epileptologists on a series of test cases with
      known epileptic seizures. In this way we assessed the accuracy of the DRFs in
      classifying patients with epileptic seizures. RESULTS: We included sixty-six
      patients in this efficacy study. The patients and/or their relatives described
      the manifestations occurring during a seizure. Sixty cases (91%) were correctly
      classified using the decision support system. DISCUSSION: The accuracy of 91 %
      indicates that the knowledge encoded in the DRFs for the included seizure types
      is valid. The next step is to test the DRFs in a clinical setting to evaluate the
      applicability in daily practice.

PMID- 16283102
TI  - Fatal cerebral hemorrhage in mitochondrial encephalomyopathy. Clinical and
      pathological data of a case.

PMID- 16283103
TI  - Diagnostic MR imaging features of craniocerebral Aspergillosis of sino-nasal
      origin in immunocompetent patients.
AB  - BACKGROUND: Craniocerebral invasive Aspergillosis of sino-nasal origin has been
      reported with a very high mortality due to a peculiarly fulminant clinical
      course. Early diagnosis based on clinical radiological imaging may have an impact
      on final clinical outcome. This retrospective study focuses on characteristic MR
      imaging features of Aspergillosis (of sinonasal origin) in immunocompetent
      patients. METHODS: Medical records of patients were reviewed retrospectively
      during the period from 1991 to 2003 in the two tertiary care hospitals. All the
      patients had radiological evidence of disease in the paranasal sinuses with or
      without intracranial extension. Immunocompetence of patients was assessed on
      clinical and radiological data. MRI scans (n=20) were reviewed by both clinical
      neurosurgeons and neuroradiologists separately. MRI was done on 1.5 tesla
      scanners and both T2-weighted and T1 weighted sequences were obtained followed
      gadolinium enhanced images. Patients were categorized into three types based on
      their anatomical location on MRI scans; type-1 being intracerebral, type-2 as
      intracranial extradural and type-3 invading orbit and/or skull base only. All
      these patient had the epicenter of disease in the nose and/or paranasal sinuses
      as evident on MR imaging. All patients underwent standard surgical intervention
      followed by antifungal therapy. Clinical outcome was assessed on Glasgow outcome
      scale with mean duration of clinical follow up of 13.9 months. FINDINGS: Mean age
      of patents (n=20) was 31.1 years with male preponderance (3:1). MRI scans showed
      evidence of disease in paranasal sinuses including mucosal thickening (n=11) and
      complete filling of sinuses (n=9). T2-weighted images showed extremely hypo
      intense fungal mass (n=19) while T1-weighted images had iso-intense signals
      (n=18). Gadolinium-enhanced images showed bright homogenous contrast enhancement
      (n=18) and peripheral ring enhancement pattern (n=2). All patients underwent
      appropriated surgical procedures depending upon anatomical location followed by
      standard antifungal therapy. Tissue diagnoses were established by histopathology
      (n=20) and culture growth (n=5). Overall mortality remained 15 percent.
      INTERPRETATION: Craniocerebral Aspergillosis of sinonasal origin has typical MR
      imaging features. These features include a mass lesion producing hypo-to-iso
      intense signals on T1-weighted, extremely low signals (hypo-intense) on T2
      weighted images, with bright homogenous enhancement on post-gadolinium T1
      weighted imaging. These features in the clinical background may be helpful in
      early diagnosis and management of Aspergillosis of sino-nasal origin in
      immunocompetent hosts. Prospective clinical study is required to make firm
      clinical therapeutic recommendations.

PMID- 16283104
TI  - Management of delayed intracranial and intraspinal metastases of intradural
      spinal paragangliomas.
AB  - The preferential site of extra-adrenal paragangliomas is the head and neck
      region. However intradural spinal paragangliomas are commonly described and are
      considered as benign entities. We report the case of a paraganglioma of the cauda
      equina followed after complete surgical removal by intracranial and intraspinal
      cerebrospinal fluid metastases. Seven years after the first operation, a cystic
      cerebellar lesion was successfully treated by surgery. During a long follow-up,
      four locations in the posterior fossa, a lumbar recurrence and metastatic nodules
      at T6 and S1-S2 level were also discovered. Radiotherapy stopped the lesions'
      growth and allowed improvement of the neurological status. Through a review and
      analysis of the literature, we discuss the management of this unusual evolution.

PMID- 16283105
TI  - Development of a cavum septi pellucidi after Ommaya reservoir placement: report
      of an unusual complication.
AB  - Objective and importance. We present a complication of Ommaya reservoir placement
      that has not been previously reported. Following injection of a seemingly
      appropriately placed catheter, the patient developed seizures. Imaging studies
      showed the development and resolution of a cavum septi pellucidi. This case
      illustrates that the septum pellucidum is made of two layers and that a potential
      space exists between these layers. Caution is recommended when injecting a single
      hole ventricular catheter if the tip is against the septum pellucidum.

PMID- 16283106
TI  - Temporo-mesial epilepsy surgery: outcome and complications in 100 consecutive
      adult patients.
AB  - BACKGROUND: We studied the surgical outcome, and the complications in a group of
      100 consecutive adult patients with medically refractory epilepsy arising from
      the temporo-mesial structures. METHODS: Hundred patients were treated surgically
      between 1994 and 2003 for drug-resistant epilepsy involving the temporo-mesial
      structures. All of them underwent a comprehensive noninvasive presurgical
      evaluation. Fourty-eight of them underwent depth electrodes recordings (according
      to the Talairach's StereoElectroEncephaloGraphic (SEEG) methodology) because the
      noninvasive investigations were not congruent enough to identify the epileptic
      zone. The patients presenting with any space-occupying lesion, or with a
      cavernoma, or with a strictly lateral neocortical epileptic focus, were excluded.
      The MRI-examination was abnormal in 87 cases, displaying a hippocampal atrophy in
      69 cases. The extent of temporal resection was planned according to the results
      of the presurgical investigation in each particular patient. Consequently, this
      "tailored" resection varied from selective amygdalo-hippocampectomy (6 cases), to
      anterior temporal lobectomy (76 cases), or to total temporal lobectomy (18
      cases). FINDINGS: The mean post-operative follow-up period was 53 months. 85
      patients were found to be in Engel's class I post-operatively (free of disabling
      seizures), among them 74 were in class Ia (totally seizure free). Nine patients
      were in Engel's class II and six were in Engel's class III or IV (failures).
      There was no surgical mortality. Three patients had a postoperative hematoma; two
      patients required a shunt insertion; in three patients meningitis occurred; and
      two patients had postoperative ischaemia of the anterior choroidal artery
      territory, which resulted in a mild permanent hemiparesis. Neuropsychological
      complications are not addressed in detail in this article. CONCLUSIONS: These
      data indicate that "tailored" resective surgery for temporo-mesial epilepsy can
      be performed with a low rate of morbidity, and is highly efficacious. The use of
      invasive presurgical investigation (SEEG) may explain this high rate of success.

PMID- 16283107
TI  - Gamma interferon: a central mediator in atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disease of the vasculature with lesions
      developing in the arterial wall, frequently in the coronary and carotid arteries.
      The interaction between macrophages and lymphocytes within the atherosclerotic
      lesion microenvironment exemplifies a site where both innate and adaptive
      immunity contribute towards disease progression. As gamma interferon (IFN-gamma),
      the classic macrophage activating factor, has been localized to atherosclerotic
      lesions, this review will focus on its contribution to plaque pathology and will
      finally consider how current therapies, as exemplified by HMG CoA reductase
      inhibitors or statins, may impact this process beyond lipid lowering, in part by
      inhibiting IFN-gamma dependent processes. IFN-gamma sources within the atheroma
      as well as receptors, signaling pathways and its effects on macrophages as well
      as on vascular smooth muscle and endothelial cells will be considered.
      Therapeutic interventions targeting molecular events associated with IFN-gamma
      signaling offer novel approaches to the treatment of atherosclerosis.

PMID- 16283108
TI  - Periodontal therapy: a novel acute inflammatory model.
AB  - OBJECTIVE AND DESIGN: We designed a clinical trial at the Eastman Dental Hospital
      with the objective of developing a novel in vivo inflammatory model. SUBJECTS: We
      recruited 55 subjects suffering from severe periodontitis. TREATMENT:
      Participants received intensive periodontal therapy. METHODS: Blood samples were
      collected at baseline and 1 and 7 and 30 days after treatment and processed for a
      series of biomarkers (TNF-alpha, IL-6, CRP and Fibrinogen) by high-sensitivity
      assays and differential blood counts (standard laboratory procedures). RESULTS:
      TNF-alpha levels were significantly raised only after 1 day of therapy (P<0.01)
      whereas IL-6 (P<0.01), CRP (P<0.001) and Fibrinogen (P<0.001) concentrations
      peaked 24 hrs after and returned to baseline values within one month following
      therapy. Mild neutrophilia, monocytosis and lymphopenia were also observed.
      CONCLUSIONS: Intensive periodontal therapy induces a one week moderate
      inflammatory response and therefore it is proposed as a novel therapeutic and
      reliable non drug-induced in vivo model of acute inflammation.

PMID- 16283109
TI  - Th1 and Th2 cell responses of type 1 diabetes patients and healthy controls to
      human heat-shock protein 60 peptides AA437-460 and AA394-408.
AB  - RATIONALE: Type 1 diabetes mellitus (T1) is considered to be an immune mediated
      disease. Based on previous findings it might be suggested that heat shock protein
      60 (Hsp60) could be involved in the mediation of the development of the disease.
      Furthermore a bias toward Th1 immune response was observed in T1D patients where
      the level of Th1 cytokines was elevated, while the level of Th2 was decreased.
      AIM OF THE STUDY: To determine Th1 (IFN-gamma) and Th2 (IL-13) cytokine levels in
      T1 diabetic and control subjects as well as to determine whether there is a shift
      towards Th1 or Th2 immune response. MATERIALS AND METHODS: ELISPOT (Enzyme-linked
      ImmunoSPOT) analysis was employed to differentiate antigen specific T-cell
      responses of a Th1 (IFN-gamma) or Th2 (IL-13) type. 11 T1 diabetic patients and 9
      healthy controls were investigated. For T-cell stimulation, we used a polyclonal
      mitogen or Tetanus toxoid (TT) as positive controls and two peptide antigens
      Hsp60 AA394-408 and Hsp60 AA437-460. RESULTS: In case of Hsp60 AA437-460 we found
      significantly decreased Th2 response in patients, although there was no
      significant difference in Th1 response. In case of Hsp60 AA394-408 and positive
      controls there was no significant difference. CONCLUSION: Comparing the control
      and diabetic subjects a significant shift towards Th1 response in T1 diabetes
      mellitus for Hsp60 AA437-460 was observed.

PMID- 16283111
TI  - Peripheral blood phagocyte CD14 and CD11b expression on admission to hospital in
      relation to mortality among patients with community-acquired infection.
AB  - OBJECTIVE AND DESIGN: Prognostic value of markers of systemic inflammation were
      evaluated in patients admitted to hospital. MATERIAL: The study comprises 327
      patients with community- acquired infection verified on admission (n=290) or
      within 3-day follow-up (n=37). METHODS: On-admission levels of phagocyte
      CD11b/CD18 and CD14 expression were measured using whole blood flow cytometry.
      Clinical data were collected retrospectively from medical records. RESULTS: In
      univariate analysis, non-survivors as compared to survivors had higher age, lower
      arterial pressure, higher heart rate, and lower monocyte CD14 density. In
      multivariate analysis high age [relative mortality RR 1.05 (95% CI 1.01 to 1.08),
      p=0.016] and low CD 14 expression on monocytes [RR 7.49 (CI 1.63 to 34.33),
      p=0.01] remained predictive for the 28-day mortality. CONCLUSION: In patients
      with community-acquired infection, low on-admission level of monocyte CD14 is
      related to fatal outcome.

PMID- 16283110
TI  - TGFbeta inhibits IL-1 -induced iNOS expression and NO production in immortalized
      chondrocytes.
AB  - OBJECTIVE: The balance between anti-inflammatory (e.g. TGFbeta) and
      proinflammatory cytokines (e.g. IL-1 and TNFalpha), regulates destructive
      processes in OA cartilage. IL-1 and TNFalpha enhance nitric oxide (NO) production
      in OA cartilage through the inducible nitric oxide synthase (iNOS) pathway and NO
      mediates many of the destructive effects of these cytokines. The aim of the
      present study was to investigate the effects of TGFbeta on NO production in
      immortalized H4 chondrocytes exposed to IL-1. RESULTS: IL-1 induced NO production
      in chondrocytes through nuclear factor kappa B (NF-kappaB) sensitive and
      dexamethasone insensitive expression of iNOS. TGFbeta inhibited IL-1 -induced
      iNOS expression and NO production in chondrocytes, but it did not have any effect
      on iNOS mRNA levels. iNOS protein levels were similar in cells treated with IL-1
      or IL-1+TGFbeta when measured after 8 h incubation, whereas when measured after
      12 h and 24 h incubations, iNOS protein levels were 50% and 80% lower in cells
      treated with IL-1+TGFbeta than in cells treated with IL-1 alone. CONCLUSION:
      TGFbeta suppressed IL-1-induced iNOS expression and NO production in
      chondrocytes, probably by enhancing iNOS protein degradation. This finding
      suggests an additional mechanism for TGFbeta to counteract the destructive
      effects of IL-1 in OA.

PMID- 16283112
TI  - Temperature and moisture requirements for conidial germination of an isolate of
      Beauveria bassiana, pathogenic to Rhodnius prolixus.
AB  - The effects of temperature, relative humidity and water activity on germination
      of conidia of an isolate of Beauveria bassiana (Bals.) Vuill. pathogenic to the
      triatomine vector of Chagas' disease, Rhodnius prolixus Stal., were investigated
      in vitro. Germination occurred at temperatures between 15 degrees C and 35
      degrees C under saturated atmosphere and the optima ranged from 25 degrees C to
      30 degrees C. At the extreme temperatures tested (15 degrees C and 35 degrees C)
      the germination process was delayed, but germination rates reached more than 95%.
      Germination of B. bassiana conidia was strongly affected by moisture conditions.
      The availability of water, in both atmospheric and liquid conditions, caused
      changes in germination times as well as in germination rates. For example, at 25
      degrees C + 0.5 degrees C, germination took place within 20 h at 95.5% RH,
      whereas it needed 72 h of incubation at 90% RH. Germination times increased as
      the water activity declined from 0.96 a(w) to 0.92 a(w). Below 0.92 a(w), no
      germination was observed after a 72 h incubation time.

PMID- 16283113
TI  - A synopsis of the occurrence and pathogenicity of Phytophthora species in
      mainland China.
AB  - To date, 26 species of Phytophthora have been reported in mainland China but only
      23 are accepted as good taxa. Phytophthora nicotianae (P. parasitica) is the
      single most important species causing over 40 different plant diseases; P.
      boehmeriae is widespread attacking Gossypium, Boehmeria, Citrus, Broussonetia
      papyrifera and Pterocarya stenoptera; P. "fragariae var. oryzo-bladis" is unique
      to mainland China causing blight of Oryza sativa seedlings; P. megasperma sensu
      lato has been isolated from Glycine max, Asparagus officinalis and Spinacia
      oleracea. In Hainan Province, P. heveae is present in the soil without causing
      apparent diseases to Hevea brasiliensis there.

PMID- 16283114
TI  - Colonization pattern of aquatic hyphomycetes on leaf packs in subtropical stream.
AB  - Steralized leaf pieces of eight plants (Eucalyptus rostrata, Phoenix dactylifera,
      Phragmites australis, Musa nana, Salix subserrata, Cyperus alopecuroides, Ricinus
      communis and Eichhornia crassipes) were submerged in the Nile stream. Thirty-nine
      species of aquatic hyphomycetes were colonized on the plant leaves. Eucalyptus
      was the best substratum (30 species) for colonization by aquatic hyphomycetes.
      Phoenix (14 species), Phragmites (11 species), Salix (9 species), Musa (8
      species), Ricinus and Cyperus (6 species) were also good substrata for aquatic
      hyphomycetes colonization. Echhornia (aquatic plant) was not suitable for aquatic
      hyphomycetes colonization. Alatospora acuminata, Triscelophorus monosporus and
      Tetracladium marchalianum were found to be the major colonizers on all leaf
      materials. Temperature and dissolved oxygen were the highest physico-chemical
      parameters affecting the aquatic hyphomycetes colonization. These results
      indicate that aquatic hyphomycetes have been shown to be successful colonizers on
      plants leaf in river Nile in Egypt as subtropical region.

PMID- 16283116
TI  - Theoretical study of DHEA: comparative HF and DFT calculations of the electronic
      properties of a complex between DHEA and serotonin.
AB  - Molecular parameters (interatomic distances and angles, total atomic charge,
      dipole moments) of DHEA (Dehydroepiandrosterone), serotonin and of their putative
      complex including its heat of formation, have been computed in an ab initio
      comparative study involving HF and DFT calculations. The 6-31G* basis set and the
      B3LYP functional were employed. The aim of this study is to emphasize by DFT
      calculation the possible existence of a complex between DHEA and serotonin that
      may have the properties of a new drug. A Natural Bond Orbital analysis
      description offers supplementary details for the structure of the molecular units
      and their interaction.

PMID- 16283115
TI  - Methane-oxidizing bacteria in a Finnish raised mire complex: effects of site
      fertility and drainage.
AB  - Methane-oxidizing bacteria (MOB) are the only biological sinks for methane (CH4).
      Drainage of peatlands is known to decrease overall CH4 emission, but the effect
      on MOB is unknown. The objective of this work was to characterize the MOB
      community and activity in two ecohydrologically different pristine peatland
      ecosystems, a fen and a bog, and their counterparts that were drained in 1961.
      Oligotrophic fens are groundwater-fed peatlands, but ombrotrophic bogs receive
      additional water and nutrients only from rainwater. The sites were sampled in
      August 2003 down to 10 cm below the water table (WT), and cores were divided into
      10-cm subsamples. CH4 oxidation was measured by gas chromatography (GC) to
      characterize MOB activity. The MOB community structure was characterized by
      polymerase chain reaction-denaturing gradient gel electrophoresis (DGGE) and
      sequencing methods using partial pmoA and mmoX genes. The highest CH4 oxidation
      rates were measured from the subsamples 20-30 and 30-40 cm above WT at the
      pristine oligotrophic fen (12.7 and 10.5 micromol CH4 dm-3 h-1, respectively),
      but the rates decreased to almost zero in the vicinity of WT. In the pristine
      ombrotrophic bog, the highest oxidation rate at 0-10 cm was lower than in the fen
      (8.10 micromol CH4 dm-3 h-1), but in contrast to the fen, oxidation rates of 4.5
      micromol CH4 dm-3 h-1 were observed at WT and 10 cm below WT. Drainage reduced
      the CH4 oxidation rates to maximum values of 1.67 and 5.77 micromol CH4 dm-3 h-1
      at 30-40 and 20-30 cm of the fen and bog site, respectively. From the total of 13
      pmoA-derived DGGE bands found in the study, 11, 3, 6, and 2 were observed in the
      pristine fen and bog and their drained counterparts, respectively. According to
      the nonmetric multidimensional scaling of the DGGE banding pattern, the MOB
      community of the pristine fen differed from the other sites. The majority of
      partial pmoA sequences belonged to type I MOB, whereas the partial mmoX bands
      that were observed only in the bog sites formed a distinct group relating more to
      type II MOB. This study indicates that fen and bog ecosystems differ in MOB
      activity and community structure, and both these factors are affected by
      drainage.

PMID- 16283117
TI  - An ab initio study of the guanidinium groups in saxitoxin.
AB  - Quantum chemical (Hartree-Fock) calculations were performed on neutral and
      protonated saxitoxin in order to obtain optimum geometries, rotational energy
      barriers for the guanidinium ions and proton affinities. For comparison purposes,
      as model compounds, guanidinium systems in five and six membered rings were also
      investigated. In addition, DFT (B3LYP) calculations with the 6-31G** basis set
      were performed and the sodium affinities of the guanidinium groups in saxitoxin
      were obtained. It was concluded that the inhibition of the sodium channels by the
      saxitoxin is due to the interaction of the guanidinium group with carboxylate
      groups from the wall of the channel and not to the binding of the sodium ions.

PMID- 16283118
TI  - Synthesis, DFT calculations, linear and nonlinear optical properties of binuclear
      phthalocyanine gallium chloride.
AB  - The axially substituted binuclear GaCl/GaCl phthalocyanine 1 with an
      unsymmetrical pattern of substitution has been prepared and its nonlinear optical
      (NLO) properties determined. The resulting binuclear complex retains
      approximately the same transition energies of monomeric (RO)8PcGaCl as far as the
      linear optical spectrum is concerned, although 1 has a double concentration of
      central atoms per molecule and an enlarged conjugated ligand. The lack of
      significant spectral shifts in passing from mononuclear to binuclear complexes
      has been rationalized theoretically by means of density functional theory
      calculations. The purpose of the present study is to determine whether
      binuclearity affects the optical limiting behavior of 1 with respect to monomeric
      (RO)8PcGaCl in the NLO regime determined by nanosecond laser pulses.

PMID- 16283119
TI  - Bond torsion affects the product distribution in the photoreaction of retinal
      model chromophores.
AB  - Ab initio molecular dynamics (MD) calculations have been performed to study the
      photoisomerization of a 3-double-bond retinal model chromophore, the all-trans-4,
      6-dimethylpenta-3, 5-dieniminium cation, and the possible influence of non-planar
      distortions on the product distribution. In total, 171 trajectories have been
      generated for four different conformations of the structure, a planar one and
      three in which the C4-C5 and the C5=C6 bonds were increasingly twisted out of
      plane. Starting geometries randomly distributed about the equilibrium geometry
      were generated by zero-point energy sampling; trajectories were calculated using
      CASSCF-BOMD methodology and were followed until the photoproduct and its
      configuration could be assigned. For the latter, two different approaches were
      applied, one involving the CASSCF configuration vectors, the other an analysis of
      the MD at the first possible hopping event. Isomerization was found to occur
      almost exclusively about the central C3=C4 double bond in the case of the planar
      model compound. Twisting the conjugated pi-system shifts the isomerization site
      from the central double bond to the terminal C5=C6 double bond. With both the C4
      C5 and the C5=C6 bonds twisted by 20 degrees, about 35% of the trajectories lead
      to the configurationally inverted 5-cis product. The results are discussed with
      reference to the highly selective and efficient photo-induced isomerization of
      the retinal chromophore in rhodopsin.

PMID- 16283120
TI  - The first intermediates in the bromination of
      bicyclo[3.3.1]nonylidenebicyclo[3.3.1]nonane, combination of experiments and
      theoretical results.
AB  - Bicyclo[3.3.1]nonylidenebicyclo[3.3.1]nonane (1) and adamantylideneadamantane
      (Ad=Ad) are two caged olefins with closely related structures at the double bond.
      Both compounds react instantaneously with Br2 in chlorinated hydrocarbon solvents
      to give mixtures of olefin-Br2 aggregates identified as the 1:1 pi-complex and
      bromonium tribromide, bromonium pentabromide ion pairs. The stoichiometry,
      formation constants and the electronic spectra of all the species present at
      equilibrium (pi-complex and bromonium ions), obtained by addition of bromine to
      alkene 1, have been determined in 1,2-dichloroethane at 25 degrees C and compared
      with the values that characterize the corresponding aggregates arising from
      Ad=Ad. The absence of the two bridging CH2 groups in 1 significantly affects all
      the formation constants. Moreover, at variance with Ad=Ad, olefin 1 reacts with
      bromine to give, depending on reagent concentration, a substitution product. DFT
      (B3LYP) and ONIOM computations of 1:1 Br2-olefin complexes for 1 and Ad=Ad
      confirm that the association energy is larger for the complex 1-Br2. The higher
      stability of this species seems to be correlated to the greater IP of 1 with
      respect to Ad=Ad which is able to compensate the reduced polarizability. The
      experimental value of the formation constant found for the complex 1-Br2, 643 vs
      289 M(-1) further supports the primary role exerted by dispersion interactions in
      alkene-Br2 pi-complexes.

PMID- 16283121
TI  - Prediction of toxicity using a novel RBF neural network training methodology.
AB  - A neural network methodology based on the radial basis function (RBF)
      architecture is introduced in order to establish quantitative structure-toxicity
      relationship models for the prediction of toxicity. The dataset used consists of
      221 phenols and their corresponding toxicity values to Tetrahymena pyriformis.
      Physicochemical parameters and molecular descriptors are used to provide input
      information to the models. The performance and predictive abilities of the RBF
      models are compared to standard multiple linear regression (MLR) models. The
      leave-one-out cross validation procedure and validation through an external test
      set produce statistically significant R2 and RMS values for the RBF models, which
      prove considerably more accurate than the MLR models. [Figure: see text].

PMID- 16283122
TI  - [Slow growth rate of mycobacteria. Possible reasons and significance for their
      pathogenicity].
AB  - A characteristic feature of mycobacteria is their slow growth rate, which in
      addition strongly varies in different species of the genus. All highly pathogenic
      species such as M. tuberculosis and M. leprae causing tuberculosis and leprosy,
      respectively, belong to the slow growing mycobacteria, while the apathogenic and
      opportunistic species are members of the fast growing mycobacteria. This suggests
      that the question be posed whether there is causality between mycobacterial
      growth rate and virulence. We discuss possible reasons for the slow and variable
      growth rates of mycobacteria and the current state of knowledge concerning the
      significance of slow growth for mycobacterial pathogenicity.

PMID- 16283123
TI  - [Cardiovascular high-risk constellations in primary care. DETECT Study 2003].
AB  - DETECT is a nationwide epidemiological cross-sectional and longitudinal study
      program in a random probability sample of 3,795 primary care settings (response
      rate: 60.2%). Based on a target day total assessment of n=55,518 consecutive
      patients (RR 93.5%) in these settings all patients underwent standardized
      diagnostic assessment, using self-reporting, clinical interview and laboratory
      measures. DETECT aims at describing the point prevalence and comorbidity of
      coronary heart disease (CHD), hyperlipidaemia, arterial hypertension and diabetes
      mellitus and at identifying the behavioural, clinical, laboratory and
      psychological risk factors associated with these conditions. A random subset of
      patients (n=7,519) also completed an extensive standardized laboratory screening
      program and a 12-month follow-up investigation. Findings reveal a high prevalence
      of hypertension (36.3%), dyslipidaemia (29.1%), diabetes mellitus (14.6%) and CHD
      (12.4%) in primary care as well as their close association among each other. The
      study describes for the first time in greater detail the prevalence of specific
      disorders and the frequency of high-risk constellations in primary care and
      allows for the evaluation of various risk scores.

PMID- 16283124
TI  - [Contact allergens in the standard patch test series from 1980-2004 at the
      University Clinic Aachen].
AB  - Allergic contact dermatitis is a common disease whose specific therapy is
      avoidance of allergens. It is critical to identify frequency of occurrence of
      allergic reactions to initiate preventive measures (e.g. elimination of
      substances with an especially high allergic potential). This study analyzes
      results of patch testing performed between 1980 and 1993 at the University Clinic
      of the RWTH Aachen. Additionally, age and sex-related distribution was evaluated.
      The data is compared to published patch test results covering the years 1995-2001
      and patch test results from 2004 in the University Clinic Aachen.

PMID- 16283125
TI  - [In vitro testing for allergic contact dermatitis].
AB  - Patch testing is the standard method to identify allergic contact dermatitis.
      Simple, safe and accurate in vitro methods identifying contact allergies would
      offer both theoretical and practical advantages. Using the lymphocyte
      transformation test (LTT), allergen-specific lymphocytes central to the
      pathogenesis of Type IV allergies can be identified. Various studies have
      assessed the value of LTT in the diagnosis of contact allergies. The current
      assessment is that the test can be helpful in distinguishing between irritant and
      allergic reactions. LTT is especially useful in demonstrating drug allergies and
      can also be employed to prove sensitization to gases or toxic substances. At the
      present time, it is not an alternative for patch testing in daily practice.

PMID- 16283126
TI  - [Atopy patch testing with aeroallergens and food].
AB  - The atopy patch test (APT), a patch test employing allergens known to elicit IgE
      mediated reactions which is assessed by evaluating eczematous skin lesions after
      24 h to 72 h, was developed as a diagnostic tool for characterizing patients with
      aeroallergen-triggered atopic eczema (AE, atopic dermatitis). Positive APT
      reactions are associated with allergen-specific T-cell responses. The specificity
      of APT is higher than the specificity of skin prick tests or RAST. More studies
      for the standardization of APT methods are necessary, especially with regard to
      food APT.

PMID- 16283127
TI  - [Topical therapy of ulcers].
AB  - Therapy of ulcers includes both treating the ulcer itself and the underlying
      disease. Local or surgical wound therapy depends on the phase of the wound
      healing. Physiological wound healing can be divided into three phases: the
      cleansing phase, the granulation phase and the epithelialization phase. The
      choice of the optimal therapy also depends on degree of secretion, bacterial
      contamination and anatomical location, as well as size and depth of the wound.
      While dry wound therapy was performed years ago, moist wound therapy is well
      established today. There are a large number of modern wound dressings for local,
      phase-dependent or phase-independent ulcer therapy, making the optimal treatment
      of each kind of chronic wound possible.

PMID- 16283128
TI  - [Patch testing with the DKG standard series 2001-2004. Results from the IVDK].
AB  - Patch testing is the standard procedure to detect contact sensitivity. The most
      frequent contact allergens are included in the standard series. We report on
      current trends regarding results obtained with the standard series from 2001-2004
      in Germany, Austria (Graz, Vienna) and Switzerland (Basel). This analysis
      includes the frequency of the most common contact allergens and other aspects
      such as age and gender distribution and parameters of diagnostic quality such as
      reaction index and positivity ratio. Information on the most common contact
      allergens is updated.

PMID- 16283129
TI  - [Hemorrhagic dengue fever after trip to Malaysia].
AB  - A 39-year-old patient developed a disseminated rash with scattered petechiae,
      fever, malaise and arthralgia after a trip to Malaysia. The patient displayed
      increasing dengue IgG titers and borderline dengue IgM titers. Dengue fever with
      a hemorrhagic course is a rare condition in adult patients. Patients who have
      previously had dengue fever and retained non-neutralizing heterotypic antibodies
      are more likely to develop this complication via the phenomenon of antibody
      dependent enhancement.

PMID- 16283130
TI  - [Massive epistaxis with haemorrhagic shock in the late phase after skull-base
      fracture].

PMID- 16283131
TI  - [The influence of conductive hearing loss on DPOAE-threshold. The effect of an
      individually optimized stimulation].
AB  - BACKGROUND: The DPOAE-threshold, estimated from extrapolated I/O functions,
      allows an objective assessment of the mechanical sensitivity of the inner ear. In
      children, the specificity of this diagnostic tool is impaired by conductive
      hearing loss. METHODS: In this study, we propose an individual optimization of
      the primary tone level ratio. This procedure allows the detection of a conductive
      hearing loss that can be accounted for when estimating the DPOAE-threshold. By
      means of a simulation using DPOAE-data from 22 normally hearing subjects, the
      effects of this procedure on the estimation of the DPOAE-threshold are examined.
      RESULTS: An individually optimized DPOAE stimulation distinctly improves the
      signal-to-noise ratio of the DPOAE which enables an estimation of the DPOAE
      threshold for sound conductive losses up to 15 dB. The DPOAE-threshold only
      worsens in individual cases. CONCLUSIONS: An individually optimized stimulation
      paradigm may improve the specificity of inner ear diagnostics with the DPOAE
      threshold. A clinical evaluation of the method in children, however, is
      necessary.

PMID- 16283132
TI  - [Diagnosis and treatment of insect venom allergy. An important allergic issue for
      the ear, nose and throat specialist].
AB  - The increasing incidence and the potentially life-threatening reactions to venom
      stings indicate the necessity for otolaryngologists to have a basic knowledge of
      the diagnosis and treatment of venom allergy. The diagnosis of insect venom
      allergy is based on the history, skin prick testing (ideally performed as a
      titration series), and in vitro analysis of specific IgE antibodies to venoms. An
      emergency medication kit should be prescribed for the patient in case of future
      venom stings, comprising an H1-blocking antihistamine, a steroid and an
      adrenaline pen for self-injection. Subcutaneous allergen-specific immunotherapy
      (sSIT) is the standard treatment to avoid allergic reactions following venom
      stings in the future. SIT is indicated following all immediate-type reactions to
      venom stings; contraindications relate to the general recommendations of allergen
      specific immunotherapy. Aqueous as well as alum-adsorbed depot allergen
      preparations can be used for subcutaneous injections. The important dose-increase
      phase can be performed using conventional, cluster, rush or ultra-rush schedules.
      Specific immunotherapy is successful in nearly 90% to 100% of patients after 3-5
      years of treatment.

PMID- 16283133
TI  - [Frequency specific auditory evoked responses. Experiments on stimulus polarity,
      sweep frequency, stimulus duration, notched-noise masking level, and threshold
      estimation in volunteers with normal hearing].
AB  - Auditory evoked responses to tone-pips in notched-noise provide frequency
      specific estimations of thresholds. Most often, test frequencies are 0.5-4 kHz.
      Thresholds are expected to match with a high degree to behavioral thresholds.
      However, only few studies are available containing data on stimulus and averaging
      parameters, especially at a test frequency of 0.25 kHz. In order to find
      "optimal" parameters for a widely used device (Nicolet Spirit Version 1.6), we
      designed five experiments on stimulus polarity (Exp.I), sweep frequency (Exp.II),
      stimulus duration (Exp.III), notched noise level (Exp.IV), and threshold
      estimation (Exp.V). The experiments also included a low test frequency of 0.25
      kHz. These experiments were applied to 29 healthy volunteers (n=29, aged 20-41
      years with normal hearing and no history of illness of the ear). We found that
      alternating stimulus polarity and a sweep frequency of 43.5/s evoked responses
      that were highest with respect to amplitudes (0.2-0.4 mV) and correlations (0.49
      0.91). A novel finding of the study was that the highest amplitudes and
      correlations could be achieved if stimulus durations and notched-noise-levels
      were specifically adjusted to the test frequencies (stimulus durations 0.25 kHz:
      4 ms, 0.5 Hz: 2 ms, 1-4 kHz: 1 ms, notched-noise-levels 0.25-0.5 Hz: +10 dB, 1-4
      kHz: +/-0 dB). Deviations from behavioral thresholds did not exceed +/-5 dB in
      93% of the measures. The results indicate that frequency specific auditory evoked
      responses provide reliable threshold estimations. Future experiments are required
      to confirm the threshold deviations for hard of hearing individuals.

PMID- 16283135
TI  - [Mitral regurgitation].
AB  - Mitral regurgitation is the second most frequent reason for valve surgery. The
      most important causes of mitral regurgitation are degenerative valve disease
      (mitral valve prolapse), left ventricular impairment and dilatation (in coronary
      artery disease or dilated cardiomyopathy), and infective endocarditis. The
      regurgitation of blood from the left ventricle into the left atrium leads to
      dilatation of the left atrium, increase in pulmonary capillary pressure and
      pulmonary congestion. In chronic severe mitral regurgitation, the left ventricle
      dilates and becomes impaired over time. Key symptoms are fatigue and dyspnea on
      exertion. The most prominent physical sign is the characteristic systolic murmur.
      Echocardiography identifies severity, delineates morphology, and estimates the
      impact of mitral regurgitation on left ventricular function. Importantly,
      echocardiography identifies candidates for mitral valve repair. Symptomatic
      patients and asymptomatic patients with impaired left ventricular function should
      be operated. If possible, valve repair is preferred over valve replacement to
      better preserve left ventricular function and to avoid the need for postoperative
      anticoagulation (except if atrial fibrillation persists).

PMID- 16283134
TI  - [Molecular diagnosis of diabetes mellitus].
AB  - Diabetes mellitus comprises a heterogeneous group of disorders characterized by
      chronic hyperglycemia. Type 1 and type 2 diabetes result from alterations of
      various genes, each having partial and additive effects. Thus, the inheritance
      pattern is rather complex, and environmental factors play an important role in
      the manifestation and clinical course of the disease. There is no genetic test to
      diagnose diabetes mellitus type 1 or type 2. However, certain susceptibility
      genes and genetic variations can be examined for specific scientific questions.
      Furthermore, defined genetic defects exist of pancreatic beta-cell function
      (maturity-onset diabetes of the young, mitochondrial diabetes) and insulin action
      (e.g. insulin resistance syndromes and lipodystrophy syndromes) resembling
      monogenic disorders. In these cases, genetic tests are crucial for the correct
      classification of the type of diabetes, genetic counseling, and initiation of the
      appropriate therapy regimen.

PMID- 16283137
TI  - [Therapeutic options of chronic constipation].
AB  - Chronic constipation is a widespread disease affecting up to 25 percent of the
      population in western countries. The symptoms associated with constipation may
      lead to a heavy burden and a decrease in quality of life. The therapy of chronic
      constipation is based upon its type and severity. Patients with normal transit
      may benefit from lifestyle measures including dietetic advice. However, almost
      none of these measures has been validated in a controlled trial. Bulk forming
      laxatives such as psyllium seeds and probiotics have a moderate evidence (Grade
      B). In certain cases, the use of osmotic laxatives, e. g. polyethylene glycol
      solutions (Grade A), is necessary. Tegaserod, a selective agonist of the
      serotonine subtype 4 (5-HT(4)), has a good evidence to treat constipation (Grade
      A). Patients with slow-transit constipation (transit-time over 72 hours) are
      dependent on osmotic (polyethylene glycol solutions, Grade A) and stimulant
      laxatives (bisacodyl, Grade C). Patients who suffer from defecatory disorders
      (outlet constipation) should be treated with bulk forming laxatives (Grade B)
      together with suppositories (e. g. CO(2)-suppositories) and enemas.

PMID- 16283138
TI  - [Chest pain, reduced physical activity, and polyserositis in a 35-year old
      patient with anticonvulsive medication].
AB  - We report on a rare case of a late-onset drug-induced lupus erythematosus. A 35
      year old male patient complained about dyspnea, chest pain and reduced physical
      activity for three months. His medical history consisted of epilepsy treated with
      carbamazepine for 20 years. After diagnosis of a large pericardial effusion and
      percardiocentesis (1200 ml) the diagnosis of viral perimyocarditis was suspected.
      Under antiphlogistic treatment the symptoms vanished initially. Four weeks later
      the pericardial effusion recurred and a livedo reticularis became evident. A
      structural or infectious heart disease, in particular viral myocarditis, was
      ruled out invasively. Serologic testing revealed antinuclear antibodies and
      antibodies against histones without presence of antibody against ds-DNA, thereby
      confirming the diagnosis of carbamazepine-induced lupus erythematodes. After
      discontinuation of carbamazepine and immunosuppressive medication the patient
      recovered completely.

PMID- 16283139
TI  - Gene expression profiling of Japanese psoriatic skin reveals an increased
      activity in molecular stress and immune response signals.
AB  - Gene expression profiling was performed on biopsies of affected and unaffected
      psoriatic skin and normal skin from seven Japanese patients to obtain insights
      into the pathways that control this disease. HUG95A Affymetrix DNA chips that
      contained oligonucleotide arrays of approximately 12,000 well-characterized human
      genes were used in the study. The statistical analysis of the Affymetrix data,
      based on the ranking of the Student t-test statistic, revealed a complex
      regulation of molecular stress and immune gene responses. The majority of the 266
      induced genes in affected and unaffected psoriatic skin were involved with
      interferon mediation, immunity, cell adhesion, cytoskeleton restructuring,
      protein trafficking and degradation, RNA regulation and degradation, signalling
      transduction, apoptosis and atypical epidermal cellular proliferation and
      differentiation. The disturbances in the normal protein degradation equilibrium
      of skin were reflected by the significant increase in the gene expression of
      various protease inhibitors and proteinases, including the induced components of
      the ATP/ubiquitin-dependent non-lysosomal proteolytic pathway that is involved
      with peptide processing and presentation to T cells. Some of the up-regulated
      genes, such as TGM1, IVL, FABP5, CSTA and SPRR, are well-known psoriatic markers
      involved in atypical epidermal cellular organization and differentiation. In the
      comparison between the affected and unaffected psoriatic skin, the transcription
      factor JUNB was found at the top of the statistical rankings for the up-regulated
      genes in affected skin, suggesting that it has an important but as yet undefined
      role in psoriasis. Our gene expression data and analysis suggest that psoriasis
      is a chronic interferon- and T-cell-mediated immune disease of the skin where the
      imbalance in epidermal cellular structure, growth and differentiation arises from
      the molecular antiviral stress signals initiating inappropriate immune responses.

PMID- 16283140
TI  - S-CMC-Lys-dependent stimulation of electrogenic glutathione secretion by human
      respiratory epithelium.
AB  - Glutathione (GSH) is one of the most important defense mechanisms against
      oxidative stress in the respiratory epithelial lining fluid. Considering that GSH
      secretion in respiratory cells has been postulated to be at least partially
      electrogenic, and that the mucoregulator S-carbocysteine lysine salt monohydrate
      (S-CMC-Lys) can cause an activation of epithelial Cl(-) conductance, the purpose
      of this study was to verify whether S-CMC-Lys is able to stimulate GSH secretion.
      Experiments have been performed by patch-clamp technique, by high-performance
      liquid chromatography (HPLC) assay, and by Western blot analysis on cultured
      lines of human respiratory cells (WI-26VA4 and CFT1-C2). In whole-cell
      configuration, after cell exposure to 100 microM S-CMC-Lys, a current due to an
      outward GSH flux was observed, which was inhibitable by 5-nitro-2-(3
      phenylpropylamino)-benzoate and glibenclamide. This current was not observed in
      CFT1-C2 cells, where a functional cystic fibrosis transmembrane conductance
      regulator (CFTR) is lacking. Inside-out patch-clamp experiments (GSH on the
      cytoplasm side, Cl(-) on the extracellular side) showed the activity of a
      channel, which was able to conduct current in both directions: the single channel
      conductance was 2-4 pS, and the open probability (P(o)) was low and voltage
      independent. After preincubation with 100 microM S-CMC-Lys, there was an increase
      in P(o), in the number of active channels present in each patch, and in the
      relative permeability to GSH vs Cl(-). Outwardly directed efflux of GSH could
      also be increased by protein kinase A, adenosine 5'-triphosphate, and cyclic
      adenosine monophosphate (cAMP) added to the cytoplasmic side (whole-cell
      configuration). The increased secretion of GSH observed in the presence of S-CMC
      Lys or 8-bromoadenosine-3',5'-cyclic monophosphate was also confirmed by HPLC
      assay of GSH on a confluent monolayer of respiratory cells. Western blot analysis
      confirmed the presence of CFTR in WI-26VA4 cells. This study suggests that S-CMC
      Lys is able to stimulate a channel-mediated GSH secretion by human respiratory
      cells: electrophysiological and pharmacological characteristics of this channel
      are similar to those of the CFTR channel.

PMID- 16283141
TI  - A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher
      syndrome.
AB  - Homozygosity mapping and linkage analysis in a Turkish family with autosomal
      recessive prelingual sensorineural hearing loss revealed a 15-cM critical region
      at 17q25.1-25.3 flanked by the polymorphic markers D17S1807 and D17S1806. The
      maximum two-point lod score was 4.07 at theta=0.0 for the marker D17S801. The
      linkage interval contains the Usher syndrome 1G gene (USH1G) that is mutated in
      patients with Usher syndrome (USH) type 1g and encodes the SANS protein. Mutation
      analysis of USH1G led to the identification of a homozygous missense mutation
      D458V at the -3 position of the PDZ binding motif of SANS. This mutation was also
      present homozygously in one out of 64 additional families from Turkey with
      autosomal recessive nonsyndromic hearing loss and heterozygously in one out of
      498 control chromosomes. By molecular modeling, we provide evidence that this
      mutation impairs the interaction of SANS with harmonin. Ophthalmologic
      examination and vestibular evaluation of patients from both families revealed
      mild retinitis pigmentosa and normal vestibular function. These results suggest
      that these patients suffer from atypical USH.

PMID- 16283142
TI  - Association of angiotensin-converting enzyme 2 (ACE2) gene polymorphisms with
      parameters of left ventricular hypertrophy in men. Results of the MONICA Augsburg
      echocardiographic substudy.
AB  - Angiotensin-converting enzyme (ACE) activity is considered to be of major
      importance for the conversion of angiotensin (Ang) I to Ang II. Recently, a
      second ACE, named ACE2, has been identified. Experimental data provide evidence
      that ACE2 might be involved in modulating cardiac structure and function. In the
      present explorative study, we assessed whether polymorphisms in the ACE2 gene are
      related to echocardiographically determined parameters of left ventricular mass,
      structure or function in the general population. Five intronic single nucleotide
      polymorphisms (SNPs) were genotyped using the 5'-exonuclease activity (TaqMan)
      assay in the echocardiographic substudy of the third MONICA Augsburg survey. As
      ACE2 is located on the X chromosome, women and men were analysed separately. Four
      SNPs showed high pairwise linkage disequilibrium (rs4646156, rs879922, rs4240157
      and rs233575). The minor alleles of these four SNPs were associated with higher
      left ventricular mass index (LVMI) and higher septal wall thickness (SWT) in men.
      Likewise, male carriers of a common haplotype (frequency 29.9%) consisting of the
      minor alleles of these four SNPs displayed higher values for LVMI and SWT than
      non-carriers (LVMI: TGGC 98.8+/-1.52 vs non-TGGC 94.8+/-0.99 g/m(2), p=0.027;
      SWT: TGGC 11.5+/-0.14 vs non-TGGC 11.1+/-0.09 mm, p=0.019). Furthermore, this
      haplotype was associated with an increased odds ratio (OR) for left ventricular
      hypertrophy (OR 3.10, p=0.006). In women, similar but less pronounced and
      consistent trends were observed. No association was observed between any of these
      SNPs and parameters of left ventricular systolic or diastolic function nor with
      blood pressure levels. This study provides evidence that genetic variants in the
      ACE2 gene may be associated with left ventricular mass, SWT and left ventricular
      hypertrophy in hemizygous men.

PMID- 16283143
TI  - RNA interference: ready to silence cancer?
AB  - RNA interference (RNAi) is considered the most promising functional genomics tool
      recently developed. As in other medical fields, this biotechnology might
      revolutionize the approach to dissecting the biology of cancer, ultimately
      speeding up the discovery pace of novel targets suitable for molecularly tailored
      antitumor therapies. In addition, preclinical results suggest that RNAi itself
      might be used as a therapeutic weapon. With the aim of illustrating not only the
      potentials but also the current limitations of RNAi as a tool in the fight
      against cancer, here we summarize the physiology of RNAi, discuss the main
      technical issues of RNAi-based gene silencing, and review some of the most
      interesting preclinical results obtained so far with its implementation in the
      field of oncology.

PMID- 16283145
TI  - Targeting protein-protein interactions for cancer therapy.
AB  - An increasing number of protein-protein interactions have been identified as
      potential intervention points for the development of anticancer agents. However,
      such systems have historically been considered high-risk targets due to the
      relatively large interaction surfaces involved in protein-protein binding. This
      characterization has to be reexamined as progress has been made recently in
      identifying small-molecule inhibitors of several protein-protein systems in
      oncology including the p53-MDM2 interaction. This review presents a survey of
      protein-protein interactions that have been identified as potential oncology
      targets and evaluates their attractiveness in terms of drug discovery. The
      analysis focuses primarily on the structural characteristics of the participating
      binding sites, particularly the dimensions of the sites. Known ligands are also
      examined, especially with regard to their druglikeness.

PMID- 16283144
TI  - Inhibition of Notch/RBP-J signaling induces hair cell formation in neonate mouse
      cochleas.
AB  - Mammalian inner ear hair cells in cochleas are believed to be incapable of
      regeneration after birth, which hampers treatment of sensorineural hearing
      impairment mainly caused by hair cell loss. Sensory epithelia of cochleas are
      composed of hair cells and supporting cells, both of which originate from common
      progenitors. Notch/RBP-J signaling is an evolutionally conserved pathway involved
      in specification of various cell types in developmental stage and even in some of
      postnatal mammalian organs. The specification of hair cell fate from the
      progenitors is inhibited by Notch/RBP-J signaling in embryonic inner ears.
      However, its function in postnatal inner ears is unknown. We showed that
      inhibition of Notch/RBP-J signaling, by either conditional disruption of the
      Rbpsuh gene or treatment with a gamma-secretase inhibitor, could give rise to
      ectopic hair cells in the supporting cell region in organs of Corti from neonatal
      mouse cochleas where hair cells have not been considered to regenerate after
      birth. We also showed that down-regulation of Hes5 and up-regulation of Math1
      were associated with ectopic hair cell induction. These results suggest that
      Notch/RBP-J signaling inhibits supporting cells from differentiation into hair
      cells even in postnatal days, implying that inhibitors of Notch/RBP-J signaling
      can be used to help regenerating hair cells after birth and thus serve for
      potential treatment of intractable sensorineural hearing impairment caused by
      hair cell loss without genetical manipulation.

PMID- 16283146
TI  - Molecular features and clinical phenotypes in androgen insensitivity syndrome in
      the absence and presence of androgen receptor gene mutations.
AB  - Androgen insensitivity syndrome (AIS) is characterized by deficient or absent
      virilization in 46,XY individuals despite normal or even elevated androgen
      levels. AIS is usually caused by mutations in the androgen receptor (AR) gene. We
      aimed at contrasting clinical, biochemical, and molecular genetic characteristics
      of three patients (P1-P3) with clinically evident partial (P1) and complete (P2,
      P3) AIS with and without AR gene mutations. AR expression was studied in cultured
      genital skin fibroblasts (GSF) by Western immunoblotting, ligand binding
      analyses, Northern blotting, semiquantitative reverse transcription-polymerase
      chain reaction (RT-PCR), and RT-PCR spanning exons 1-8. AR gene DNA sequence was
      analyzed by single-strand conformation analysis (SSCA), and DNA sequencing. GSF
      revealed reduced (P1) or absent (P2, P3) ligand binding. Northern blots showed
      either slightly reduced hybridization of the 10.5-kb AR transcript (P3) or no
      hybridization (P1, P2), as confirmed by semiquantitative RT-PCR. RT-PCR spanning
      exons 1-8 detected single AR mRNA bands in P1-P3 excluding splicing errors.
      Western analyses showed either low (P1) or no (P2, P3) AR protein. While SSCA
      initially did not reveal any molecular abnormality, sequencing showed a novel CAG
      (Gln) to TAG (stop) mutation at codon 59 (P3) and a previously described 2-bp
      deletion at codon 472, leading to a frameshift and premature stop in codon 499
      (P2). Intriguingly, P1 showed an unaltered DNA sequence of the coding region of
      the AR gene including all intron-exon boundaries. In conclusion, patients with
      clinically evident complete AIS are likely to harbor an AR gene mutation,
      demanding that the two polymorphic regions must always be included in molecular
      analyses of the AR gene. Moreover, our data support the concept that in a subset
      of AIS patients, particularly those with partial AIS, molecular alterations
      outside the coding region of the AR gene must be presumed.

PMID- 16283148
TI  - [Effects of high-dose cortisone therapy on cognition].
AB  - Treatment with high-dose corticosteroids over 3-5 days reduces the duration and
      severity of relapses in patients with multiple sclerosis. Since the benefit of
      this treatment appears to be dose-dependent, application of ultrahigh steroid
      doses becomes important. On the other hand, data from basic research and clinical
      studies indicate potential side effects on mnestic functions. Three recently
      published studies show that treatment with pulsed corticosteroids induces
      reversible impaired memory. The effects were independent of the dose
      administered.

PMID- 16283147
TI  - Hereditary breast and ovarian cancer: review and future perspectives.
AB  - Breast cancer (BC) is the most frequent carcinoma in women. The cumulative risk
      for the disease is 10% up to the age of 80 years. A familial history of BC and
      ovarian cancer (OC) is a significant risk factor. Some 5-10% of all cases of BC
      and 25-40% of cases in patients under the age of 35 years have a hereditary
      origin. BRCA1/BRCA2 mutations are responsible for 3-8% of all cases of BC and 30
      40% of familial cases. Ten percent of patients with OC have a genetic
      predisposition. About 80% of families with a history of OC have BRCA1 mutations,
      while 15% have BRCA2 mutations. Women at risk can receive counseling from
      interdisciplinary cancer genetics clinics, while those at high risk can receive
      genetic testing. Risk calculation programs can define the risks and assist in
      decision making for genetic testing and clinical options. Clinical options
      require information on the risks of the disease and its mutation status.
      Chemoprevention is currently a controversial topic, while the use of oral
      contraceptives can be regarded as reducing the risk for OC. Prophylactic
      mastectomy and bilateral ovariectomy are the only options that lead to a
      demonstrable reduction in risk, but they do, of course, affect the patient's
      physical integrity. It is not currently known whether intensified early cancer
      detection is individually beneficial, but this is currently the option that is
      the least invasive and least burdensome to the patient. Although hereditary BC
      has different pathological characteristics and the BRCA mutation is an
      independent negative prognostic factor, there are currently no special treatment
      guidelines. Without adjuvant hormone therapy or chemotherapy, the overall
      survival in BRCA mutation carriers is reduced. Chemotherapy regimens involving
      platinum are particularly beneficial in the treatment of hereditary BC.

PMID- 16283149
TI  - [Hypertrophic cranial pachymeningitis as a rare cause of headache].
AB  - Hypertrophic cranial pachymeningitis is an uncommon, fibrosing, inflammatory
      process that involves the dura mater. The condition is being reported more
      frequently owing to the use of cranial MRI. The main clinical feature is
      headache, whereas cranial nerve lesions, cerebellar symptoms, and epileptic
      seizures occur more rarely. A variety of autoimmune and infectious diseases can
      result in this condition, which is labeled as idiopathic in the absence of any
      definite inciting factor. The diagnosis of hypertrophic cranial pachymeningitis
      is based on neuroimaging of thickened and enhancing dura mater. It can be defined
      pathologically on biopsy. A specific treatment is indicated in some cases of
      secondary hypertrophic cranial pachymeningitis. Mostly, treatment relies on
      corticosteroids and immunosuppressive agents. This review summarizes the current
      knowledge on causes, clinical presentation, diagnosis, and treatment of this
      disorder.

PMID- 16283150
TI  - [Multislice computed tomographic myelography].
AB  - While magnetic resonance imaging (MRI) is the first line modality in depicting
      intramedullary spinal lesions, computed tomographic (CT) myelography has gained
      renewed attention due to the introduction of multislice scanning (MS-CT).
      Compared with conventional CT, MS-CT permits rapid, high-resolution imaging of
      various spinal pathologies with extended scan length. Although soft tissue
      contrast is inferior to that with MRI, MS-CT myelography performs best in
      detailed assessment of osseous pathologies, 3D imaging of orthopedic and
      anesthesiologic implants, and showing dural leakage and causes of CSF circulation
      impairment. Whenever MRI is not available or contraindicated, MS-CT myelography
      is the method of choice for evaluating spinal lesions.

PMID- 16283151
TI  - [Medication treatment for Parkinson's disease].
AB  - In general, therapy for Parkinson's disease is dominated by dopamine agonists
      (DA) in younger patients and levodopa in older patients with comorbidities.
      Single or combined treatment with DA should be used as long as possible to avoid
      levodopa and associated complications. About 30% of our patients respond to DA
      monotherapy and tolerate it for quite a long time. It is important to sustain
      patient confidence. Although parkinsonism is an insidious disease of unknown
      cause resulting in destruction of important dopaminergic neurons, no other
      neurodegenerative disease can be treated as successfully.

PMID- 16283153
TI  - [Neoadjuvant chemotherapy of breast carcinomas: what post-therapeutic
      (preoperative) information is provided by quantitative dynamic MRI?].
AB  - PURPOSE: The aim of this study was to evaluate whether quantitative changes in
      contrast enhancement (CE) after neoadjuvant chemotherapy (NC) are associated with
      histological signs of tumor regression and whether quantitative dynamic MRI
      (dMRI) is capable of accurately assessing preoperative tumor size compared to
      mammography (MG) and ultrasound (US). METHODS: Thirty-one patients with breast
      cancer underwent MRI before and after NC. Dynamic CE was measured using a turbo
      FLASH sequence and quantified by a two-compartment model, where two parameters,
      k(ep) (distribution constant rate) and A (amplitude), were calculated and color
      mapped. RESULTS: When tumors had signs of histological regression in the
      operative specimen (n=17) decrease of the parameters A and k(ep) was
      significantly more marked compared to tumors without regression (n=12). The
      correlation between tumor size measured by dMRI and histopathology was 0.81 when
      areas of unspecific CE were included; when they were not included the correlation
      was 0.66 and tumor size was systematically underestimated. In 26 patients dMRI
      was retrospectively compared with MG (r=0.51; dMRI, r=0.80) and in 22 patients
      with US (r=0.60; dMRI, r=0.75). CONCLUSION: Changes in dynamic CE are associated
      with histological tumor regression. Quantitative dMRI enables a valid assessment
      of tumor residue and is superior to MG and US. Remaining unspecific CE within the
      original tumor site should be considered as potentially malignant.

PMID- 16283152
TI  - [Hypertensive encephalopathy: differential diagnosis of brain edema with midline
      shift].
AB  - Hypertensive encephalopathy is a severe complication of hypertensive crisis or
      malignant hypertonia. We report a case with grave clinical and radiological
      features. The patient was comatose, with pupillary dysfunction, and initial CT
      suggested a local intracranial mass with edema. Cranial MRI showed almost
      completely hyperintensive supratentorial white matter, with edema and midline
      shift, and hypertensities in cerebellum and brainstem. The patient recovered, and
      the radiological findings improved after antihypertensive therapy. Hypertensive
      encephalopathy may be differentiated by MRI, manifests acutely, and is
      potentially reversible when adequate therapy is rapidly performed.

PMID- 16283154
TI  - [Study activities for testicular cancer].
AB  - Testicular cancer is one of the few tumors which are curable even at an advanced
      stage. This has been achieved both by the use of platinum based chemotherapy and
      by the interdisciplinary approach by urologists, internal oncologists and radio
      oncologists. In 1988, the Interdisciplinary Testicular Cancer Study Group was
      founded. The aim of this group is to initiate clinical trials to improve the
      results in the treatment of this tumor. Furthermore, the group has published
      evidenced-based national and international guidelines for testicular cancer. This
      article gives an overview on the work of the group including current studies.

PMID- 16283155
TI  - [Consequences of the 12th AMG amendment on the conduct of non-commercial clinical
      trials].
AB  - In 2004, the German Drug Law was reformed substantially putting into effect the
      European directive 2001/20/EG on Good Clinical Practice (GCP). Investigator
      initiated trials have to comply with the same requirements as clinical trials for
      drug development. When registered drugs are used in non-commercial clinical
      trials some simplifications are possible.Currently, all essential elements of
      GCP, such as financing of the trial, laying-down of sponsor responsibilities,
      establishing an extensive quality assurance system as well as immediate reporting
      of unexpected serious drug reactions, are stipulated by law. Since regulatory
      authorities and ethics committees have to approve every clinical trial,
      surveillance is reinforced. The new requirements cannot be met without sufficient
      financing, qualified personnel and professional structures for clinical trials.
      Compared to European partners, the research location Germany is at a disadvantage
      due to high administrative workload and costs.

PMID- 16283156
TI  - [Peyronie's disease Current conservative and non-invasive treatment options.]
AB  - Peyronie's disease is an aetiologically poorly understood disease of the tunica
      albuginea, characterized by pain during erection, development of fibrous plaques
      and penile curvature. Due to incomplete understanding of the pathophysiology of
      the disease, no causal treatment exists. In the literature, there are many
      conservative treatment proposals. This report describes the conservative and
      minimally invasive treatment options for Peyronie's disease.

PMID- 16283157
TI  - Further restrictions for ICU research.

PMID- 16283158
TI  - Statins: the next step in adjuvant therapy for sepsis?

PMID- 16283159
TI  - Statin therapy is associated with fewer deaths in patients with bacteraemia.
AB  - OBJECTIVE: Beneficial effects with statin use are increasingly reported in a
      variety of patient groups. There is in vitro and clinical evidence for its
      antiinflammatory and immunomodulatory therapeutic roles. We aimed to assess the
      association between statin administration and mortality in bacteraemic patients.
      DESIGN: A retrospective cohort analysis. SETTING: A 300-bed acute general
      hospital. PATIENTS AND PARTICIPANTS: All patients (n=438) requiring hospital care
      for an episode of bacteraemia during the years 2000-2003 were included. Statin
      use, patient outcome, and clinical and laboratory variables were collected.
      INTERVENTIONS: None. MEASUREMENTS AND RESULTS: There was a significant reduction
      in all-cause hospital mortality (10.6% vs. 23.1%, p=0.022) and death attributable
      to bacteraemia (6.1% vs. 18.3%, p=0.014) in patients who were receiving statin
      therapy at the time of bacteraemia (n=66). The reduction in all-cause hospital
      mortality (1.8% vs. 23.1%, p=0.0002) and death attributable to bacteraemia (1.8%
      vs. 18.3%, p=0.0018) was more pronounced in the patients who continued to receive
      statin therapy after the diagnosis of bacteraemia (n=56). The apparent mortality
      benefit persisted after controlling for differences between the groups. Statin
      use prior to admission was associated with a reduced adjusted hospital mortality
      rate (odds ratio 0.39; CI 95% 0.17, 0.91; p=0.029), and continuing statin use
      after bacteraemia increased this effect (odds ratio 0.06; CI 95% 0.01, 0.44;
      p=0.0056). CONCLUSION: This retrospective study demonstrates a significant
      survival benefit associated with continuing statin therapy in bacteraemic
      patients. The potential for statins as an adjuvant therapy in sepsis warrants
      further investigation.

PMID- 16283160
TI  - Trends in sedation practices in Danish intensive care units in 2003: a national
      survey.
AB  - OBJECTIVE: The aim of the study was to explore trends and changes in sedation
      practices for mechanically ventilated patients in Danish intensive care units
      (ICUs) and to compare sedation practices in 1997 and 2003. DESIGN: The study was
      a follow-up survey with a descriptive and comparative cross-sectional multicenter
      design. SETTING: Questionnaires were mailed in January 2003 to all Danish ICUs
      providing mechanical ventilation (n=48). PARTICIPANTS: One head physician at each
      ICU in Denmark. INTERVENTIONS, MEASUREMENTS, AND RESULTS: Thirty-nine
      questionnaires were returned, yielding a response rate of 81%, representing 82%
      of Danish ICU beds. The main findings were a significant increase in the use of
      sedation scoring systems and a significant reduction of sedation and analgesia in
      relation to various modalities of mechanical ventilation and disease groups.
      Other important findings were a significant reduction in the use of
      benzodiazepines and opioids and a significant increase in the use of propofol in
      relation to all ventilator modes. The administration routes of sedative agents
      remained unchanged. CONCLUSIONS: Sedatives and analgesics are still widely used
      in Danish ICUs. The trend is toward lighter sedation along with a shift from
      benzodiazepines toward propofol and from morphine toward fentanyl given by
      continuous infusion. More attention needs to be directed toward sedation
      standards and scoring systems in order to reduce the risk associated with
      sedation in mechanically ventilated patients.

PMID- 16283161
TI  - Lung "recruitment" or lung overinflation maneuvers?

PMID- 16283163
TI  - Mechanical ventilation for patients with ARDS: a UK survey on calculation of
      tidal volume.

PMID- 16283162
TI  - Weaning from mechanical ventilation with pressure support in patients failing a T
      tube trial of spontaneous breathing.
AB  - OBJECTIVE: Evidence that PS may facilitate weaning from mechanical ventilation
      (MV), although not confirmed by randomized trials, prompted us to investigate
      whether patients could be weaned with PS after failing a T-tube trial. DESIGN AND
      SETTING: This was a prospective, non-randomized study in two French intensive
      care units. PATIENTS AND PARTICIPANTS: One hundred eighteen patients were
      enrolled and underwent a T-tube trial, after which 87 were extubated. Thirty-one
      underwent a further trial with PS, after which 21 were extubated. INTERVENTIONS:
      All patients under MV >24 h meeting the criteria for a weaning test underwent a
      30-min T-tube trial. If this was successful, they were immediately extubated.
      Otherwise, a 30-min trial with +7 cm H2O PS was initiated with an individualized
      pressurization slope and trigger adjustment. If all weaning criteria were met,
      the patients were extubated; otherwise, MV was reinstated. MEASUREMENTS AND
      RESULTS: The extubation failure rate at 48 h did not differ significantly between
      the groups: 11/87 (13%) versus 4/21 (19%), P=0.39. The groups were comparable
      with regard to endotracheal tube diameter, MV duration, the use of non-invasive
      ventilation (NIV) after extubation, initial severity score, age and underlying
      pathology, except for COPD. A significantly higher percentage of patients with
      COPD was extubated after the trial with PS (8/21-38%) than after a single T-tube
      trial (11/87-13%) (P=0.003). CONCLUSIONS: Of the patients, 21/118 (18%) could be
      extubated after a trial with PS, despite having failed a T-tube trial. The
      reintubation rate was not increased. This protocol may particularly benefit
      patients who are most difficult to wean, notably those with COPD.

PMID- 16283165
TI  - Comment on "Early treatment with activated protein C for meningococcal septic
      shock: case report and literature review" by Hasin et al.

PMID- 16283166
TI  - Favourable issue of a fulminant hepatitis associated with sulfasalazine DRESS
      syndrome without liver transplantation.

PMID- 16283168
TI  - ICU physicians, end-of-life care, and the law.

PMID- 16283169
TI  - Comment on "A new device for administration of continuous positive airway
      pressure in preterm infants" by Trevisanuto et al.

PMID- 16283171
TI  - Bedside waveforms interpretation as a tool to identify patient-ventilator
      asynchronies.
AB  - OBJECTIVE: During assisted modes of ventilatory support the ventilatory output is
      the final expression of the interaction between the ventilator and the patient's
      controller of breathing. This interaction may lead to patient-ventilator
      asynchrony, preventing the ventilator from achieving its goals, and may cause
      patient harm. Flow, volume, and airway pressure signals are significantly
      affected by patient-ventilator interaction and may serve as a tool to guide the
      physician to take the appropriate action to improve the synchrony between patient
      and ventilator. This review discusses the basic waveforms during assisted
      mechanical ventilation and how their interpretation may influence the management
      of ventilated patients. The discussion is limited on waveform eye interpretation
      of the signals without using any intervention which may interrupt the process of
      mechanical ventilation. DISCUSSION: Flow, volume, and airway pressure may be used
      to (a) identify the mode of ventilator assistance, triggering delay, ineffective
      efforts, and autotriggering, (b) estimate qualitatively patient's respiratory
      efforts, and (c) recognize delayed and premature opening of exhalation valve.
      These signals may also serve as a tool for gross estimation of respiratory system
      mechanics and monitor the effects of disease progression and various therapeutic
      interventions. CONCLUSIONS: Flow, volume, and airway pressure waveforms are
      valuable real-time tools in identifying various aspects of patient-ventilator
      interaction.

PMID- 16283173
TI  - The extensor mechanism of the knee joint: an anatomical study.
AB  - This study investigated the anatomy of the structures that form the extensor
      mechanism of the knee joint using microsurgical techniques. Ten fresh-frozen
      human adult cadaveric knees were used. The quadriceps components, the
      infrapatellar tendon, the patellofemoral ligaments, and their relations to the
      neighboring anatomical structures were measured. The angles of the vastus
      lateralis and the vastus medialis muscle fibers to the rectus tendon were 26.6
      and 41.1 degrees , respectively. The medial patellofemoral ligament connecting
      the femoral medial epicondyle to the medial edge of the patella was approximately
      54.2 mm long, and its width ranged from 9 to 30 mm. The medial patellomeniscal
      ligament had a wide attachment to the meniscus whereas the attachment to the
      patella was narrow. The patellar tendon was 31.9 mm broad at its attachment to
      the apex of the patella and 27.4 mm wide at its attachment to the tibial
      tubercle. It was 38-49 mm long. Using the surgical microscope we were able to
      dissect and identify a trilaminar arrangement of prepatellar fibrous soft
      tissues. Also, we were able to identify the vessels and nerves around the
      patella. Details of clinical relevance and the possible pathological implications
      of the material presented are discussed. Emphasis is placed on the stability of
      the patellofemoral joint and the complex interaction between a range of factors
      providing it.

PMID- 16283172
TI  - Femoral attachment of the anterior cruciate ligament.
AB  - Endoscopic anterior cruciate ligament (ACL) reconstruction is one of the most
      popular orthopaedic procedures. Correct tunnel positioning is a prerequisite to
      success. Current surgical techniques are unable to duplicate the complex anatomy
      and function of the native ACL. Surgery mainly aims at restoring anteroposterior
      laxity. The ACL is not isometric and only a few fibers are nearly isometric over
      the full range of motion. However, a nearly isometric behaviour of the ACL graft
      is desirable. Isometry is mainly influenced by femoral attachment; thus the
      femoral tunnel position has a greater effect than the tibial on graft length
      changes. The purpose of this article is to describe the anatomy of the femoral
      ACL insertion and to discuss the surgical techniques used to replicate it.

PMID- 16283174
TI  - Intra-articular fibroma of tendon sheath involving the scapholunate and
      radiocarpal joints.
AB  - Fibroma of tendon sheath is an uncommon benign soft tissue tumor with a
      predilection for the hand. A unique case involving the scapholunate and
      radiocarpal joints with bone erosion is reported. The patient presented with a
      transilluminating mass over the volar radial wrist associated with neuropathy in
      the superficial radial nerve distribution. Magnetic resonance imaging
      demonstrated a heterogeneous and lobulated mass with nonspecific signal
      characteristics closely associated with the scapholunate interval and the volar
      wrist soft tissues. Histologically it represented a fibroma of tendon sheath. The
      tumor is discussed and the relevant literature is reviewed.

PMID- 16283175
TI  - Gastric cancer acrometastases to all digits of one hand following closed
      intramedullary nailing.
AB  - Metastatic malignant tumor of the hand is unusual and the most common site of the
      primary cancer is lung. Acrometastases to the phalanges of the hand usually
      involve a single bone, while those proximal to the phalanges often involve
      multiple bones. Metastasis to the hand from gastrointestinal cancer, particularly
      from gastric cancer, is extremely rare. To our knowledge, only five cases have
      been reported in the literature to date and there has been no reported case
      following closed intramedullary nailing for metastatic diaphyseal fracture of an
      ipsilateral long bone. We present a very unusual case of gastric cancer, which
      metastasized to all fingertips of the ipsilateral hand after closed interlocking
      intramedullary nailing of a pathologic fracture of the humerus.

PMID- 16283176
TI  - Chronic expanding hematoma of the thigh simulating neoplasm on gadolinium
      enhanced MRI.
AB  - Patients who present with slowly growing extremity masses are often imaged with
      MRI to be examined for possible tumors. In addition to cysts and neoplasms,
      chronic expanding hematomas should be considered in the differential diagnosis if
      the patient has a history of remote trauma. The presence or absence of internal
      contrast enhancement is often used to distinguish between hematomas and
      hemorrhagic neoplasms on MRI and CT. We present the unusual case of a patient who
      had a chronic expanding hematoma of the calf that demonstrated nodular internal
      enhancement on gadolinium-enhanced MRI, simulating a neoplasm.

PMID- 16283177
TI  - Lipomatosis of the sciatic nerve: typical and atypical MRI features.
AB  - Lipomatosis of nerve, also known as fibrolipomatous hamartoma, is a rare
      condition of nerve, usually affecting the median nerve. The MRI appearance is
      characteristic. We describe two cases of lipomatosis of nerve involving the
      sciatic nerve, an extremely unusual location for this lesion, in patients with
      sciatic neuropathy. These cases share the typical features previously described
      in the literature for other nerves, but also contain atypical features not
      previously highlighted, relating to the variability in distribution and extent of
      the fatty deposition. Recognition of the MRI appearance of this entity is
      important in order to avoid unnecessary attempts at surgical resection of this
      lesion.

PMID- 16283179
TI  - "Ecstasy"-induced neurotoxicity: the contribution of functional brain imaging.

PMID- 16283180
TI  - PET is better than perfusion SPECT for early diagnosis of Alzheimer's disease --
      against.

PMID- 16283181
TI  - PET is better than perfusion SPECT for early diagnosis of Alzheimer's disease --
      for.

PMID- 16283182
TI  - One life to live, but many ways to die--imaging of cardiomyocyte death.

PMID- 16283183
TI  - (99m)Tc-annexin V and (111)In-antimyosin antibody uptake in experimental
      myocardial infarction in rats.
AB  - PURPOSE: (99m)Tc-annexin V (ANX) allows scintigraphic detection of apoptotic
      cells via specific binding to exposed phosphatidylserine. In myocardial
      infarction, apoptosis of myocytes is variable and depends especially on the
      presence or absence of coronary reperfusion. In this study, ANX uptake in non
      reperfused experimental myocardial infarcts was compared with uptake of a marker
      of myocyte necrosis ((111)In-antimyosin antibodies, AM) and an
      immunohistochemical marker of apoptosis (Apostain). METHODS: The left anterior
      coronary artery was ligated in 47 Wistar rats, which were then injected with ANX
      (n=20), AM (n=21) or both (n=6). Myocardial uptake of ANX and AM was determined
      at 2 h (n=14), 4 h (n=14) and 24 h (n=19) after coronary ligation (CL), by
      quantitative autoradiography with (n=23) or without (n=24) gamma imaging. Heart
      to-lung ratios (HLRs) and infarct-to-remote myocardium activity ratios (INRs)
      were calculated on the scintigrams and autoradiograms respectively. Cardiac
      sections were stained with haematoxylin-eosin and Apostain. The above studies
      were repeated in 12 normal rats. RESULTS: All rats with CL showed increased ANX
      and AM uptake in cardiac areas on scintigrams 24 h after CL, with HLRs higher
      than in controls: 3.1+/-0.6 versus 1.5+/-0.3 (p=0.001) for ANX and 1.99+/-0.44
      versus 1.01+/-0.05 (p<0.0005) for AM. Autoradiography showed intense ANX and AM
      uptake in infarcts, with comparable topography and INRs at 2 h, 4 h and 24 h
      after CL (4.6+/-0.9 versus 5.0+/-1.8 at 24 h), while Apostain staining was very
      low (0.06+/-0.06% of cells). CONCLUSION: In this model of persistent CL, we
      observed increased ANX uptake in injured myocardium, comparable in intensity,
      topography and kinetics to that of AM. There was only minimal Apostain staining
      in the same areas.

PMID- 16283186
TI  - [Primary phacoemulsification following acute primary angle closure glaucoma].
AB  - Recent developments and clinical studies indicate that primary
      phacoemulsification and intraocular lens implantation are safe and effective for
      the surgical treatment of primary angle closure glaucoma (ACG) compared to
      conventional iridectomy or laser-iridotomy. When compared to control eyes treated
      using standard peripheral iridectomy, the outcome in terms of intraocular
      pressure control, adjunct anti-glaucoma medication, visual acuity, and the
      necessity for successive surgical interventions favored primary
      phacoemulsification and intraocular lens implantation. Earlier biometric data
      underline the importance of the "lens factor" in the pathogenesis of relative
      pupillary block in ACG obtained by Scheimflug image processing and ultrasound
      biomicroscopy. The vast improvements in modern cataract surgery combined with our
      current understanding of the pathogenesis of relative pupillary block in ACG
      indicate that lens extraction is a better procedure in uncontrolled angle closure
      glaucoma than conventional iridectomy.

PMID- 16283188
TI  - [A refractory pupil].

PMID- 16283187
TI  - [Lamellar keratoplasty. Back to the future?!].
AB  - In 1840 Muhlbauer was the first to describe a technique for anterior lamellar
      keratoplasty (LKP). However, in the second half of the twentieth century
      penetrating keratoplasty (PKP) became the gold standard. Although it is
      associated with a higher risk for serious complications -- it is technically
      easier to perform and avoids wound healing reactions in the lamellar interface
      and thus resulting in better visual acuity. In view of the pathology, replacing
      all layers of the cornea including healthy parts can be considered therapeutic
      "overkill" for many corneal graft indications. Several innovative surgical
      techniques have recently been described which allow the lamellar dissection of
      recipient and donor cornea with good reproducibility in almost every desired
      depth. This now allows the recipient endothelium and Descemet's membrane to be
      selectively replaced or preserved and to avoid formation of an optical barrier in
      the lamellar interface in eyes undergoing lamellar keratoplasty for optical
      indications. The most important principal advantage of an anterior LKP -- to
      minimize the risk of an immune reaction in the graft -- is even more important in
      tectonic indications. From the large number of variations, the surgical
      technique, results, and problems with anterior and posterior LKP for optical
      indications as well as lamellar segment keratoplasty and epikeratoplasty for
      tectonic indications are discussed.

PMID- 16283189
TI  - [Complications following contusio bulbi].

PMID- 16283190
TI  - [Is it possible to compensate for visual field defects?].
AB  - Is it possible for a driver to compensate for visual field defects by skill along
      with eye and head movements? Monocular field defects with a normal second eye are
      no problem, because a normal binocular visual field is adequate for all areas of
      traffic. A total bitemporal hemianopia creates a special situation, because the
      patient loses a three-dimensional space behind a vertical line through the point
      of fixation. He may have no binocular visual field. In this case the ability to
      participate in certain traffic situations may be limited with reduced risk
      profile. A real problem is posed by defects in the binocular visual field, e.g.,
      due to lesions of the suprachiasmal visual pathway or due to ocular diseases
      causing damage to both eyes (e.g., glaucoma, diabetic retinopathy, etc.). Such
      defects usually cannot be compensated for, neither by skill nor by eye or head
      movements. Saccadic eye movement training and other procedures are only of
      limited help. These procedures may provide some compensation for daily use; a
      complete restoration of the ability to participate in traffic is not possible.
      Rare exceptions may be patients with damage to the visual pathway acquired peri-
      or postnatally or in early childhood when there is still enough plasticity in the
      visual system to develop mechanisms of compensation by completely changing the
      system of eye and head movements.

PMID- 16283191
TI  - [Lavasept as an alternative to PVP-iodine as a preoperative antiseptic in
      ophthalmic surgery. Randomized, controlled, prospective double-blind trial].
AB  - BACKGROUND: To reduce the risk of endophthalmitis PVP-iodine is typically used
      preoperatively. Since iodine is contraindicated in patients with a specific
      allergic history or severe thyroid disorder we studied the effect of Lavasept,
      which contains Polyhexanid as an antiseptic alternative. PATIENTS AND METHODS: In
      a randomized controlled double-blind trial 3 drops of 0.2% Lavasept, 1.25% PVP
      iodine or Ringer's solution were applied preoperatively to 67 patients, which
      have had a minimum of 5 colony forming units (cfu's) in the conjunctival swap.
      The effectiveness and tolerability were measured. RESULTS: After application of
      Lavasept or PVP-iodine, the number of cfu was statistically significantly
      reduced. Lavasept reduced the number of bacterial colonies significantly better
      than PVP-iodine (p=0.05). All test solutions were equally well tolerated.
      CONCLUSION: The use af Lavasept is safe, well tolerated and reduces the
      microbiological contamination of the conjunctival fornix effectively. lt provides
      a more effective reduction of the cfu's than PVP-iodine 1.25% and this effect
      tends to be prolonged. Lavasept is a good alternative option in ophthalmology for
      preoperative antisepsis.

PMID- 16283192
TI  - [Toxic endophthalmitis].

PMID- 16283193
TI  - Childhood brain tumour information on the Internet in the Chinese language.
AB  - BACKGROUND: Internet information, now available in many different languages, can
      become a major source of information for patients and families in their own
      mother tongue. Chinese represent one of most frequently spoken language in the
      world. The aims of this study were to critically appraise the quantity and
      quality of Internet health information in childhood brain tumour in the Chinese
      language and to identify sufficient quality websites that can potentially be
      recommended to Chinese-speaking parents. METHODS: Internet information on six
      common paediatric brain tumours was searched using six commonly used Chinese
      search engines. Websites were assessed systematically using two rating tools:
      DISCERN instrument and Checklist Rating System Instrument. RESULTS: Out of 946
      sites accessed, only 13 assessable Chinese websites, displaying Traditional
      Chinese characters and providing information on brain tumour, were identified.
      Only four sites included specific discussion on brain tumours in children. Ten
      websites failed to provide satisfactory information on brain tumour as rated by
      DISCERN instrument. Overall only 41% of the 13 specific items relevant to brain
      tumours were mentioned (Checklist Rating System Instrument). CONCLUSION: Only a
      few satisfactory websites can be recommended to Chinese-speaking families for
      general information on brain tumour with caution from health care providers that
      such information may not apply to the child's individual condition.

PMID- 16283194
TI  - Congenital pineoblastoma and parameningeal rhabdomyosarcoma: concurrent two
      embryonal tumors in a young infant.
AB  - BACKGROUND: Pineoblastomas are very rare brain tumors in fetus and neonates,
      comprising only 0.9% of congenital brain tumors. The occurrence of multiple
      tumors of different histopathologic types in the same individual is a rare event,
      most often encountered in hereditary cancer syndromes. CASE REPORT: We report a
      female fetus presented with a congenital pineoblastoma at the 32nd week of
      gestation, with hydrocephalus and concurrent parameningeal embryonal
      rhabdomyosarcoma in early infancy. RESULTS: Cytogenetic analysis showed normal
      karyotype in the peripheral blood of the patient, and p53 mutational analysis
      revealed no germ line mutations. DISCUSSION: This is the first case with
      concurrent congenital pineoblastoma and parameningeal embryonal rhabdomyosarcoma
      in early infancy. We suggest that concurrence of these tumors could be due to
      mutations in other tumor suppressor genes or secondary to exposure to unknown in
      utero factors.

PMID- 16283184
TI  - [Classification of biomedical research reports as a reference for evidence-based
      medicine in ophthalmology. A survey considering as example the journal Der
      Ophthalmologe].
AB  - BACKGROUND: Evidence-based medicine requires careful appraisal of published data
      derived from experimental and clinical studies. Based on classification of
      biomedical research reports, evidence levels can be determined and
      recommendations for therapeutic decisions can be made. METHODS: A classification
      system for clinical studies was developed. It was evaluated in classifying the
      reports published in Der Ophthalmologe during 2003-2004 (study design:
      descriptive cross-sectional study, case series). RESULTS: In the 2-year interval,
      70 longitudinal and 95 cross-sectional studies were published. The vast majority
      of the longitudinal studies were interventional cohort studies. Not considering
      case reports, 73% of the original articles were longitudinal prospective studies,
      1% were retrospective (case-control) studies, and 26% were cross-sectional
      studies. CONCLUSIONS: The study design of all published articles could be
      classified using the classification system. This classification system proves to
      be applicable in the context of clinical studies in ophthalmology and may be
      helpful in the process of critical appraisal of the literature and synthesis of
      clinical evidence and an evidence-based recommendation.

PMID- 16283195
TI  - A review of clinical and histological features of Spanish paediatric
      medulloblastomas during the last 21 years.
AB  - PURPOSE: To find any feature of prognostic significance among the clinical and
      histological characteristics of paediatric patients diagnosed with
      medulloblastoma (MB). MATERIALS AND METHODS: Clinical charts and paraffin blocks
      of 79 paediatric patients from nine Spanish institutions diagnosed with MB
      between 1980 and 2001 were reviewed retrospectively. Included clinical and
      histological characteristics were age, sex, duration of symptoms, physical signs
      on admission, tumour location, T and M stages of Chang classification,
      hydrocephalus, cerebrospinal fluid shunt, surgical resection, complications after
      surgery, MB subtype, desmoplasia, nodularity, fibrilar pattern, nuclear
      pleomorphism, necrosis grade, proliferation index and intra-tumoural vascularity.
      Overall and event-free survival (EFS) univariate and multivariate analyses were
      assessed. RESULTS: Type of surgery and necrosis grade appeared to be independent
      prognostic variables in overall and EFSs. Although nuclear pleomorphism and intra
      tumoural vascularity showed a marginally statistical effect on overall survival
      (OS), both had a significant influence on EFS. CONCLUSION: We have confirmed
      surgical resection and added necrosis grade as independent prognostic factors in
      terms of OS for children diagnosed with MB.

PMID- 16283197
TI  - Abnormal facial nerve course associated with stapes fixation or oval window
      absence: report of two cases.
AB  - Congenital minor ear malformations are very uncommon. Their etiology can be
      explained by the embryological development of the middle ear structures. Their
      classification, diagnosis and treatment pose certain problems. We report on one
      case of congenital stapes fixation and one case of oval window absence, both
      associated with an abnormal facial nerve course. Good long-term results show that
      performing a platinotomy or vestibulotomy in cases of congenital stapes fixation
      or oval window absence can be a relatively safe procedure, even in presence of
      deviated facial nerve course. The literature and present classifications of minor
      ear malformations are discussed.

PMID- 16283196
TI  - Evidence for an Akt-kinase/NO/cGMP pathway in the cochlea of guinea pigs.
AB  - The protein kinase Akt (protein kinase B) can be activated by numerous growth
      factors via PI-3 kinase-generated phosphoinositides and is thought to have anti
      apoptotic properties. Activated Akt/PKB boosts the activity of endothelial NO
      synthase (NOS III), which has been found in the key areas of the inner ear (e.g.,
      hair cells and stria vascularis). In order to localize activated Akt/PKB (phospho
      Akt) in the cochlea of guinea pigs, sections of ten temporal bones were observed
      immunohistochemically. The strongest immunoreactivity was found in and underneath
      inner hair cells (IHC). Within the organ of Corti, reactivity was found in
      supporting cells, while outer hair cells remained unstained. Spiral ganglion
      cells, the endothelium of the lateral wall and the vascular area of the modiolus
      showed moderate staining. The results give evidence that activated Akt/PKB
      influences the activity of the NO/cGMP pathway in the cochlea. Because of the
      antiapoptotic properties, activated Akt should now be examined under non
      physiological conditions.

PMID- 16283198
TI  - Peripheral seventh nerve palsy due to transorbital intracranial penetrating
      pontine injury.
AB  - The case of a child injured by a knitting needle penetrating transorbitally and
      intracranially, resulting in carotid cavernous fistula and pontine injury, is
      reported. After receiving medical and endovascular treatment, the only remaining
      abnormal neurological manifestation was right peripheral facial nerve palsy. The
      clinical sequences of events and the demonstration of a pontine lesion leading to
      peripheral facial palsy are presented. Facial nuclear injury with a penetrating
      trauma is an extremely rare condition. It is important to identify the anatomical
      regions injured in penetrating traumas. The lesions must be identified by
      computerized tomography, magnetic resonance imaging, clinical and laboratory
      investigation.

PMID- 16283199
TI  - Changes in hearing aid use over the past 20 years.
AB  - The aim of this study was to find out how the use of hearing aids has been
      affected by the changes in hearing rehabilitation, hearing aids and society over
      the past 20 years. Seventy-six first-time hearing aid users were interviewed at
      their homes, and the results were compared with those of an earlier study made
      with the same method in 1983 in Finland involving both new and experienced
      hearing aid users. Hearing aid use and handling skills as well as satisfaction
      with the hearing aid were explored with interviews using the same questions in
      both studies. The number of first-time hearing aid users who did not use their
      hearing aids had decreased from 33.3% in 1983 to 5.3% at the present. Conversely,
      the number of regular users rose from 40.9 to 56.6%. The use of hearing aids was
      increased. The users were better able use their hearing aids and were more
      satisfied with them and the number of those who considered the counseling
      provided sufficient had also increased.

PMID- 16283200
TI  - Sinonasal fibro-osseous hamartoma: case presentation and differential diagnosis
      with other fibro-osseous lesions involving the paranasal sinuses.
AB  - We present the case of a 2-year-old girl who was referred to the ENT Department
      of the Antwerp University with a bony obstruction of the left side of the nose.
      The lesion originated from the ethmoid roof and the middle turbinate and extended
      into the nasopharynx. A partial functional resection was performed using an
      endoscopic approach. A combination of clinical, radiographic and histological
      information permitted a diagnosis of a benign fibro-osseous lesion: sinonasal
      hamartoma. The benign nature of this tumor justified a conservative follow-up.

PMID- 16283201
TI  - Allosteric effects of external K+ ions mediated by the aspartate of the GYGD
      signature sequence in the Kv2.1 K+ channel.
AB  - K+ channels achieve exquisite ion selectivity without jeopardizing efficient
      permeation by employing multiple, interacting K+-binding sites. Introduction ofa
      cadmium (Cd2+)-binding site in the external vestibule of Kv2.1 (drk1), allowed us
      to functionally characterize a binding site for external monovalent cations.
      Permeant ions displayed higher affinity for this site than non-permeant
      monovalent cations, although the selectivity profile was different from that of
      the channel. Point mutations identified the highly conserved aspartate residue
      immediately following the selectivity filter as a critical determinant of the
      antagonism between external K+ and Cd2+ ions. A conservative mutation at this
      position (D378E) significantly affected the open-state stability. Moreover, the
      mean open time was found to be modulated by external K+ concentration, suggesting
      a coupling between channel closing and the permeation process. Reducing the Rb+
      conductance by mutating the selectivity filter to the sequence found inKv4.1,
      also significantly reduced the effectiveness ofRb+ ions to antagonize Cd2+
      inhibition, thereby implicating the selectivity filter as the site at which
      K+ions exert their antagonistic effect on Cd2+ block. The equivalent of D378 in
      KcsA, D80, takes part in an inter-subunit hydrogen-bond network that allows D80to
      functionally interact with the selectivity filter. The results suggest that
      external K+ ions antagonize Cd2+inhibition (in I379C) and modulate the mean open
      time(in the wild-type Kv2.1) by altering the occupancy profile of the K+-binding
      sites in the selectivity filter.

PMID- 16283202
TI  - Regulation of K-Cl cotransport by protein phosphatase 1alpha in mouse
      erythrocytes.
AB  - The K-Cl cotransport (KCC) is an electroneutral-gradient-driven-membrane
      transport system, which is involved in regulation of red cell volume. Although
      the regulatory cascade of KCC is largely unknown, a signaling pathway involving
      phosphatases and kinases has been proposed. Here, we investigated the expression
      and the activity of protein phosphatase 1(PP-1) isoforms in mouse red cells,
      focusing on two models of abnormally activated KCC: mice genetically lacking the
      two Src-family tyrosine kinases, Hck and Fgr, (hck-/-fgr-/-) and the SAD
      transgenic sickle-cell-mice. The PP-1alpha, PP-1gamma, PP-1delta isoforms were
      expressed at similar levels in wild-type, hck-/-fgr-/- and SAD mouse erythrocytes
      and in each case were predominantly localized to cytoplasm. The PP-1alpha
      activity was significantly higher in both membrane and cytosol fractions of hck-/
      fgr-/- and of SAD erythrocytes than in those of wild-type red cells, suggesting
      PP-1alpha as a target of the Hck and Fgr kinases. The PP2, a specific inhibitor
      of Src-family kinase, significantly increased KCC activity in wild-type mouse red
      cells, but failed to modify the already increased KCC activity in SAD
      erythrocytes. The lag-time for activation of KCC was considerably reduced in both
      hck-/-fgr-/- and SAD erythrocytes, suggesting that the rate limiting activation
      steps in both strains are freed from their tonic inhibition. Sulfhydryl reduction
      by dithiothreitol (DTT) lowered KCC activity only in SAD red cells, but did not
      affect the PP2-treated erythrocytes. These data suggest up-regulation of KCC in
      SAD red cells is mainly secondary to oxidative damage, which most likely reduces
      or removes the tonic KCC inhibition resulting from PP-1alpha activity controlled
      in turn by Src-family kinases.

PMID- 16283203
TI  - Prediction of glycylsarcosine transport in Caco-2 cell lines expressing PEPT1 at
      different levels.
AB  - H(+)-coupled peptide transporter 1 (PEPT1) and the basolateral peptide
      transporter mediate the absorption of small peptides and peptide-like drugs in
      the small intestine. Recently, we constructed a mathematical model to simulate
      glycylsarcosine (Gly-Sar) transport in Caco-2 cells. In this study, we attempted
      to adjust our model to a change in the expression level of PEPT1. To obtain cell
      lines expressing PEPT1 at different levels, recloning of Caco-2 cells was
      performed, and nine clones were isolated. Compared with parental cells, clones 1
      and 9 exhibited the lowest and the highest levels of [(14)C]Gly-Sar uptake from
      the apical side, respectively, whereas activities of the basolateral peptide
      transporter were comparable. Kinetic analysis demonstrated that the difference in
      the activity of PEPT1 was accounted by variations in V (max). Moreover, PEPT1
      mRNA level was positively related to the activity of [(14)C]Gly-Sar uptake
      (r=0.55). Based on these findings, the V (max) value of PEPT1 was defined as a
      variable using the amount of PEPT1 mRNA as an index of the expression level. With
      this improved model, Gly-Sar transport in clones 1 and 9 was well-predicted,
      suggesting that our model can simulate Gly-Sar transport in cells expressing
      PEPT1 at different levels.

PMID- 16283204
TI  - Activation and inactivation kinetics of a Ca2+-activated Cl- current: photolytic
      Ca2+ concentration and voltage jump experiments.
AB  - The activation kinetics of the endogenous Ca(2+)-activated Cl(-) current (I
      (Cl,Ca)) from Xenopus oocytes was investigated in excised "giant" membrane
      patches with voltage and Ca(2+) concentration jumps performed by the photolytic
      cleavage of the chelator DM-nitrophen. Currents generated by photolytic Ca(2+)
      concentration jumps begin with a lag phase followed by an exponential rising
      phase. Both phases show little voltage dependence but are Ca(2+)-dependent. The
      lag phase decreases from about 10 ms after a small Ca(2+) concentration jump (0.1
      microM) to less than 1 ms after a saturating concentration jump (55 microM). The
      rate constant of the rising phase is half-maximal at about 5 microM. At
      saturating Ca(2+) concentrations, the rate constant is 400 to 500 s(-1). The
      Ca(2+) dependence of the stationary current can be described by the Hill equation
      with n=2.3 and K (0.5)=0.5 microM. The amplitude of the stationary current
      decreases after the excision of the membrane patch with t (1/2) approximately 5
      min (run-down). The activation kinetics of the current elicited by a Ca(2+)
      concentration jump is not affected by the run-down phenomenon. At low Ca(2+)
      concentration (0.3 microM), voltage jumps induce a slowly activating current with
      voltage-independent time-course. Activation is preceded by an initial transient
      of about 1-ms duration. At saturating Ca(2+) levels (1 mM), the initial transient
      decays to a stationary current. The transient can be explained by a voltage
      dependent inactivation process. The experimental data reported here can be
      described by a linear five-state reaction model with two sequential voltage
      dependent Ca(2+)-binding steps, followed by a voltage-independent rate-limiting
      transition to the open and a voltage-dependent transition to a closed,
      inactivated state.

PMID- 16283205
TI  - VIP receptors control excitability of suprachiasmatic nuclei neurones.
AB  - The role of vasoactive intestinal polypeptide (VIP) receptors on excitable
      properties of neurones in slices acutely prepared from the suprachiasmatic nuclei
      (SCN) of wild-type (WT) and VPAC(2)-receptor-deficient (Vipr2 ( -/- )) mice was
      studied under voltage clamp with the use of patch-clamp recording in the whole
      cell configuration. The resting membrane potential in Vipr2 ( -/- ) neurones was
      significantly hyperpolarised as compared to WT cells (-60+/-7 vs -72+/-6 mV,
      p<0.01). Bath application of 100 nM VIP or the VPAC(2) receptor agonist RO 25
      1553 triggered a slow inward current in a subpopulation of WT SCN neurones; the
      VIP-induced current was not affected by slice incubation with 25 microM of
      bicuculline but disappeared completely when the cells were dialysed with CsCl
      containing/K(+)-free solution. Application of VIP or RO 25-1553 to neurones from
      Vipr2 ( -/- ) mice did not induce currents in all cells tested. Incubation of WT
      slices with 100 nM VIP or RO 25-1553 resulted in inhibition of fast tetrodotoxin
      sensitive sodium currents and delayed rectifier K(+) currents in most of the
      cells tested. This effect was completely absent in cells from Vipr2 ( -/- ) mice.
      We postulate that VIP receptors control excitability of SCN neurones at the
      postsynaptic level by direct modulation of membrane potential via inhibition of
      K(+) channels and by tonic inhibition of sodium and potassium voltage-gated
      currents.

PMID- 16283206
TI  - Evidence that TRPC1 contributes to calcium-induced differentiation of human
      keratinocytes.
AB  - External calcium ion concentration is a major regulator of epidermal keratinocyte
      differentiation in vitro and probably also in vivo. Regulation of calcium-induced
      differentiation changes is proposed to occur via an external calcium-sensing,
      signaling pathway that utilizes increases in intracellular calcium ion
      concentration to activate differentiation-related gene expression. Calcium ion
      release from intracellular stores and calcium ion influx via store-operated
      calcium-permeable channels are key elements in this proposed signaling pathway;
      however, the channels involved have not yet been identified. The present report
      shows that human gingival keratinocytes (HGKs) also undergo calcium-induced
      differentiation in vitro as indicated by involucrin expression and morphological
      changes. Moreover, TRPC1, which functions as a store-operated calcium channel in
      a number of cell types, including epidermal keratinocytes, is expressed in both
      proliferating and differentiating HGKs. Transfection of HGKs with TRPC1 siRNA
      disrupted expression of TRPC1 mRNA and protein compared with transfection with
      scrambled TRPC1 siRNA. Cells with disrupted TRPC1 expression showed decreased
      calcium-induced differentiation as measured by involucrin expression or
      morphological changes, as well as decreased thapsigargin-induced calcium ion
      influx, and a decreased rate of store calcium release. These results indicate
      that TRPC1 is involved in calcium-induced differentiation of HGKs likely by
      supporting a store-operated calcium ion influx.

PMID- 16283207
TI  - [Transdermal buprenorphine during pregnancy].
AB  - Buprenorphine has been widely used and studied for over 20 years and has been
      shown to be an effective opioid analgesic. Some years ago a buprenorphine
      formulation for transdermal therapy of chronic cancer-related and non-cancer
      related pain became available. We report the case of a woman who received a lower
      dosed transdermal buprenorphine patch (3/5 of a 35 microg/h patch corresponding
      to release of 21 microg/h buprenorphine) during pregnancy without any
      complication for herself or the child. The patient has now being using the
      transdermal system for more than 2 years and has reported continuous excellent
      pain relief. The buprenorphine patch was well tolerated and produced no effect on
      vigilance over the whole period of administration.

PMID- 16283208
TI  - Is there a correlation between spirituality and anxiety and depression in
      patients with advanced cancer?
AB  - AIMS AND OBJECTIVES: To establish whether there is a correlation between
      spirituality and anxiety and depression in patients with advanced cancer.
      PATIENTS AND METHODS: Patients with a diagnosis of cancer at St. Peter's day
      hospice in Bristol were asked to complete three questionnaires to assess anxiety,
      depression and spirituality. Informed consent was obtained. Anxiety and
      depression are indicated by the Hospital Anxiety and Depression Scale score, and
      spirituality is indicated by scores on the Spiritual Well-Being Scale (SWBS) and
      the Royal Free Interview for Spiritual and Religious Beliefs. As will be
      explained, religion and spirituality are generally recognised as having different
      meanings--religion entailing a relationship with a higher being, while
      spirituality can be thought of in terms of meaning and purpose in life. RESULTS:
      Eighty-five complete data sets were obtained. A significant negative correlation
      was found between both anxiety and depression scores and overall spiritual well
      being scores (p < 0.0001). When the SWBS subscale scores were analysed
      individually, a significant negative correlation was found between the
      existential well-being scores and the anxiety and depression scores (p < 0.001).
      However, no correlation was found between the religious well-being scores and
      anxiety or depression. CONCLUSIONS: This study found a significant negative
      correlation between spirituality (in particular, the existential aspect) and
      anxiety and depression in patients with advanced cancer. Religious well-being and
      strength of belief had no impact on psychological well-being in this study.

PMID- 16283211
TI  - Differentiating imaging findings in primary and secondary tumors of the jugular
      foramen.
AB  - The preoperative diagnosis of a jugular foramen tumor may be challenging, since a
      large variety of unusual lesions may be located in this region. These tumors may
      be classified as primary lesions (which are located in the jugular foramen or
      extend from the jugular foramen into the surrounding structures) and as secondary
      lesions (that extend from the surrounding structures into the jugular foramen).
      Primary tumors include glomus jugulare tumors, schwannomas, meningiomas and
      peripheral primitive neuroectodermal tumors, while secondary tumors comprise
      chordomas, chondrosarcomas, chondroblastomas, giant-cell tumors, cholesterol
      granulomas, giant cholesterol cyst, endolymphatic sac tumors, reactive
      myofibroblastic tumors, temporal bone carcinomas and metastases. Accurate
      preoperative radiological suspicion is of great value for preoperative patient
      counseling and has a direct impact on the surgical planning in these cases. The
      present study describes and discusses the main differentiating imaging features
      of lesions involving the jugular foramen, whose accurate preoperative
      radiological evaluation is essential for proper surgical planning.

PMID- 16283212
TI  - Endoscope-assisted removal of colloid cysts of the third ventricle.
AB  - Colloid cysts are benign space-occupying lesions, which arise from the velum
      interpositum or the choroid plexus of the third ventricle and are able to produce
      symptomatic obstruction of the foramina of Monro with resultant hydrocephalus. In
      our department, we have operated on colloid cysts routinely in an endoscope
      assisted microsurgical manner via a key-hole approach. During a period of 10
      years, 28 microsurgical resections of colloid cysts of the third ventricle were
      performed. Seven patients demonstrated colloid cysts inside the third ventricle
      with obstruction of the right foramen Monro, two patients demonstrated cysts with
      obstruction of the left foramen Monro. Twelve patients suffered from cysts inside
      the third ventricle with obstruction of both foramina Monro and five patients
      demonstrated cysts lying into the third ventricle without obstruction of the
      foramina. In 21 patients no preoperative therapy was performed outside. Three
      patients had received shunt systems before in other hospitals, two patients
      received aspiration of the cysts under stereotactic conditions and two patients
      received external ventricular drains. Total removal of the cyst was achieved in
      all patients (100%). No patient received a second operation, because none had a
      recurrent cyst. All cysts were removed with the cyst wall. Overall clinical
      improvement was achieved in a long-standing period between 6 and 83 months in 27
      (96%) patients. In one patient (4%) the psychomotor disturbance was unchanged and
      no patient deteriorated. From the microsurgical point of view, the combination of
      keyhole surgery under endoscopic visual control using preexisting anatomical
      windows offers an effective minimally invasive approach.

PMID- 16283214
TI  - Candida glabrata prosthetic valve endocarditis treated successfully with
      fluconazole plus caspofungin without surgery: a case report and literature
      review.
AB  - Reported here is the case of a 72-year-old man who was diagnosed with Candida
      glabrata prosthetic mitral valve endocarditis and treated successfully with
      fluconazole plus caspofungin after he refused and was determined unfit for
      surgery. Initial treatment with intravenous amphotericin B resulted in acute
      renal impairment. Despite 8 days of intravenous fluconazole therapy, he remained
      fungemic. Caspofungin was added to the treatment regimen with subsequent
      sterilisation of blood culture. The patient was treated for 34 days with
      caspofungin and 41 days with fluconazole. He continued oral fluconazole after
      hospital discharge and remained well at follow-up 11 months later. The role of
      fluconazole and caspofungin in the treatment of Candida endocarditis is
      discussed.

PMID- 16283213
TI  - Molecular diagnostics in tuberculosis.
AB  - Molecular diagnostics in tuberculosis has enabled rapid detection of
      Mycobacterium tuberculosis complex in clinical specimens, identification of
      mycobacterial species, detection of drug resistance, and typing for
      epidemiological investigation. In the laboratory diagnosis of tuberculosis, the
      nucleic acid amplification (NAA) test is rapid and specific but not as sensitive
      as culture of mycobacteria. The primary determinant of successful NAA testing for
      tuberculosis depends on the shedding of mycobacterial DNA in secretions from
      caseating granulomas and its dissemination into sterile body fluids or tissue
      biopsies. In multibacillary diseases with a high mycobacterial load, a positive
      Ziehl-Neelsen smear with a positive NAA test is diagnostic of active
      tuberculosis, whereas a positive Ziehl-Neelsen smear with a negative NAA test in
      the absence of inhibitors would indicate nontuberculous mycobacterial disease.
      The role of the NAA test is more important in paucibacillary diseases with low
      mycobacterial loads. The presence of polymerase chain reaction (PCR) inhibitors,
      however, especially in extrapulmonary specimens, may produce false-negative
      results. Although this problem can be overcome to some extent by extra extraction
      steps, the additional processing invariably leads to the loss of mycobacterial
      DNA. To circumvent this problem, a brief culture augmentation step is carried out
      before the NAA test is performed, which can enhance the mycobacterial load while
      concomitantly diluting inhibitors, thereby maintaining the sensitivity of the
      test without excessively increasing turnaround time.

PMID- 16283215
TI  - In vitro activity of quinupristin and dalfopristin in combination and alone
      against coryneform bacteria.

PMID- 16283216
TI  - Procalcitonin in the elderly: normal plasma concentrations and response to
      bacterial infections.

PMID- 16283217
TI  - Outbreak of long-term intravascular catheter-related bacteremia due to
      Achromobacter xylosoxidans subspecies xylosoxidans in a hemodialysis unit.
AB  - Achromobacter xylosoxidans is a rare cause of bacteremia. Over a 2-week period,
      A. xylosoxidans subsp. xylosoxidans was isolated from blood cultures of four
      hemodialysis patients with long-term intravascular catheters. A culture from one
      atomizer that contained diluted 2.5% chlorhexidine, which had been used to
      disinfect the skin, yielded A. xylosoxidans subsp. xylosoxidans. No further cases
      were diagnosed once the use of this atomizer was discontinued. Five outbreak
      related strains from the four patients and the atomizer were tested by pulsed
      field gel electrophoresis (PFGE) under XbaI restriction. The isolates from the
      first three patients and the atomizer had identical PFGE patterns, confirming the
      atomizer as the source of the outbreak. The strain isolated from the fourth
      patient had six more bands than the outbreak strain and was considered possibly
      related to the outbreak strain. All patients were treated with intravenous
      levofloxacin. The catheter was removed in only one patient. The three patients in
      whom the catheter was left in place were also treated with antibiotic lock
      therapy with levofloxacin. All four patients were cured. This is believed to be
      the first reported outbreak of central venous catheter-related bacteremia due to
      A. xylosoxidans and the second reported outbreak with this organism associated
      with chlorhexidine atomizers. The use of diluted chlorhexidine via atomizers can
      be dangerous for the care of venous catheters and should be called into question.
      Patients with long-term intravascular catheter-related bacteremia due to this
      organism can be treated successfully with systemic antimicrobial therapy in
      addition to antibiotic lock therapy without catheter removal.

PMID- 16283218
TI  - Successful treatment of right-sided prosthetic valve endocarditis due to
      methicillin-resistant teicoplanin-heteroresistant Staphylococcus aureus with
      linezolid.

PMID- 16283219
TI  - Survey of neonatal candidiasis in Greece.
AB  - In order to estimate the extent of neonatal candidiasis in Greece and to identify
      trends in clinical management, the present study was conducted using a
      questionnaire directed to Greek neonatologists and pediatric infectious disease
      specialists. The respondents represented 15 hospitals in the country's seven
      largest cities, which are currently the only Greek cities with neonatal intensive
      care units. Based on the responses, the incidence of neonatal candidiasis was
      determined to be 1.87 and 1.94 cases per unit-year for the years 2001 and 2002,
      respectively. Although a shift toward the isolation of non-Candida albicans
      isolates was noted, C. albicans was still the predominant pathogenic species.
      Deoxycholate amphotericin B remains the most frequently used antifungal agent in
      neonatal units nationwide.

PMID- 16283220
TI  - Decompressive craniectomy in cerebral toxoplasmosis.

PMID- 16283222
TI  - An asymptomatic ruptured hepatic hydatid cyst case presenting with
      subdiaphragmatic gas in a traumatic patient.
AB  - Hydatid disease presents as hydatid cysts primarily in the liver and lungs.
      Although hepatic hydatid cysts (HHCs) may be asymptomatic for many years, they
      may be symptomatic due to expansion, rupture, and pyogenic infection. Rupture of
      the HHC into the biliary tract is one of the most serious complications and is
      frequently related to overenlargement of the cyst or major trauma. Patients with
      this disease usually have jaundice or fever. We report an asymptomatic HHC
      ruptured after minor trauma. While the ruptured cyst was presented as the
      subdiaphragmatic gas on the chest radiography, it was detected as a large cyst
      with multiple daughter cysts on ultrasound, computed tomography scan, and
      magnetic resonance imaging.

PMID- 16283221
TI  - Comparison of retrospectively ECG-gated and nongated MDCT of the chest in an
      emergency setting regarding workflow, image quality, and diagnostic certainty.
AB  - PURPOSE: This study aims to assess the influence of ECG-gated acquisition on
      workflow and to compare image quality and diagnostic certainty for
      retrospectively ECG-gated and nongated multidetector computed tomography of the
      chest in the emergency suite. MATERIALS AND METHODS: Thirty-two consecutive
      patients were referred for both an ECG-gated and a nongated CT to rule out
      traumatic thoracic injury (n=15) or acute aortic dissection (n=17). The time from
      the start of the transportation from the emergency suite to the CT room until the
      start of the CT scan was recorded. Using a scoring system, the image quality of
      axial images and multiplanar reformats, the presence of disease, and the
      subjective diagnostic certainty were assessed with regard to the vascular
      structures, the bone structures, and the lung parenchyma. RESULTS: The time
      needed for transportation and patient preparation was 12.1+/-1.7 min (8.1-14.5
      min). The motion artifacts of the thoracic aorta and the supra-aortic vessels
      were significantly reduced in the ECG-gated data acquisition compared with the
      nongated technique (P<0.001). Subjective diagnostic certainty for assessment of
      the aorta was significantly better using ECG gating. The image quality of the
      lung parenchyma (P<0.005), the spine (P<0.005), and the ribs (P<0.002) was
      inferior in the ECG-gated data sets but did not compromise the detection rate of
      traumatic lesions and fractures. CONCLUSION: Performing ECG gating in the
      emergency room did not slow down the diagnostic workup. ECG-gated acquisition
      performed better in the assessment of the aorta, but image quality for lung and
      bone structures was slightly reduced. Further studies are required to assess the
      influence of the imaging technique on the diagnostic outcome.

PMID- 16283223
TI  - Coronal thick CT reconstruction: an alternative for initial chest radiography in
      trauma patients.
AB  - It has been proposed that the imaging workup of trauma patients be accelerated by
      omitting the initial chest radiography (CR) and directly performing a computed
      tomography (CT); however, the baseline CR is then lacking. The purpose of this
      study was to assess if coronal thick reconstructions generated from chest CT
      could present an adequate alternative for CR. Sixty trauma patients underwent
      bedside CR and multidetector row chest CT in the emergency room. The image
      quality of thoracic anatomical structures, the diagnostic accuracy for chest
      pathology, and the depiction of indwelling devices were assessed on both
      modalities. Main pulmonary arteries and perihilar bronchi were equally visualized
      with both modalities. Central bronchi, retrocardial lung parenchyma, diaphragm,
      descending aorta, and vertebral pedicles were better visualized on thick CT
      reconstructions, whereas peripheral lung vessels were better depicted on CR
      (p<0.05). The accuracy to delineate various pathological findings did not differ
      between both modalities, except for a higher sensitivity to diagnose bronchial
      cuffing on CR (p<0.05). The location of indwelling devices was similarly and
      correctly depicted with both modalities. Coronal thick CT reconstructions provide
      a similar image quality and diagnostic accuracy compared with CR. These
      reconstructions may serve as an equivalent baseline image in trauma patients in
      whom emergency radiological evaluation has to be accelerated.

PMID- 16283224
TI  - Expression genetics and haplotype analysis reveal cis regulation of serine
      carboxypeptidase I (Cxp1), a candidate gene for malting quality in barley
      (Hordeum vulgare L.).
AB  - Using a cDNA array-based functional genomics approach in barley, several
      candidate genes for malting quality including serine carboxypeptidase I (Cxp1)
      were previously identified (Potokina et al. in Mol Breed 14:153, 2004). The gene
      was mapped as a single nucleotide polymorphism (SNP) marker on chromosome 3H
      using the Steptoe (feeding grade)xMorex (malting grade) mapping population.
      Subsequently, the relative level of Cxp1 expression was determined by real-time
      RT-PCR for each of the 134 progeny lines and mapped as a quantitative trait. Only
      one quantitative trait locus (QTL) could be identified that significantly
      influenced the level of the Cxp1 expression. The expressed QTL maps to the same
      region on chromosome 3H as does the structural gene and corresponds to a QTL for
      "diastatic power," one among several traits measured to assess malting quality.
      An analysis of 90 barley cultivars sampled from a worldwide collection revealed
      six SNPs at the Cxp1 locus, three of which display complete linkage
      disequilibrium and define two haplotypes. The Cxp1 expression level in a set of
      barley accessions showing haplotype I was significantly higher than that of
      accessions displaying haplotype II. The data provide evidence that (1) the
      expression of Cxp1 is regulated in cis and that (2) the level of diastatic power
      in the barley seed is influenced by the level of Cxp1 expression.

PMID- 16283225
TI  - A novel formulation for blood trauma prediction by a modified power-law
      mathematical model.
AB  - With the increasing use of artificial organs, blood damage has been raising ever
      more clinical concern. Blood trauma is in fact a major complication resulting
      from the implantation of medical devices and the use of life support apparatuses.
      Red blood cells damage predictive models furnish critical information on both the
      design and the evaluation of artificial organs, because their correct usage and
      implementation are thought to provide clear and rational guidance for the
      improvement of safety and efficacy. The currently adopted power-law shear-induced
      haemolysis prediction model lacks sensitivity with respect to the cumulative
      effect of previously applied stress magnitudes. An alternative model is proposed
      where a mechanical quantity was defined, able to describe the blood damage
      sustained by red cells under unsteady stress conditions, taking into account the
      load history. The proposed formulation predicted the same trend as the available
      experimental data. The obtained results have to be considered a preliminary
      validation of the basic hypothesis of this modified red blood cell damage
      prediction model. To date, the necessity to design further experiments to
      validate the proposed damage function clashes with the limitations inherent to
      current systems to get the time-varying shear stress completely under control.

PMID- 16283226
TI  - An inelastic multi-mechanism constitutive equation for cerebral arterial tissue.
AB  - Intracranial aneurysms (ICA) are abnormal saccular dilations of cerebral
      arteries, commonly found at apices of arterial bifurcations and outer walls of
      curved arterial segments. Histological evidence suggests the stages in ICA
      development include the deformation of a segment of arterial wall into a "bleb"
      with no identifiable neck region followed by the development of an aneurysm with
      a clear neck. Afterwards, the aneurysm may undergo further enlargement, possibly
      with significant biological response including calcification and thrombosis. Past
      studies of the biomechanics of cerebral aneurysm tissue have been directed at
      modeling elastic deformations of pre-existing aneurysms. Taking this approach,
      the aneurysm wall is treated as a different entity than the arterial tissue from
      which it developed. In the current work, a nonlinear, inelastic, dual-mechanism
      constitutive equation for cerebral arterial tissue is developed. It is the first
      to model the recruitment of collagen fibers and degradation of the internal
      elastic lamina, two important characteristics of early stage aneurysm formation.

PMID- 16283227
TI  - Determinants of the apnea index in a sleep center population.
AB  - We hypothesized that the increased apnea-hypopnea index (AHI) in men compared to
      women was secondary to an increased proportion of apneas in men as measured by
      the ratio of the apnea index to the apnea-hypopnea index (AI/AHI ratio), and that
      the influence of gender was independent of other demographic factors such as body
      mass index (BMI) and neck circumference (NC). Database analysis of 501 patients
      (218 men and 283 women) who underwent polysomnography between August 2001 and
      June 2003 and who were found to have an AHI of at least five events per hour was
      performed. Respiratory parameters were compared between genders. To correct for
      differences in demographic parameters, correlations were made between AHI and the
      AI/AHI ratio and age, BMI, NC, and the percentage time spent in the supine
      position (%TST-supine) followed by a regression analysis to determine which
      factors independently predicted these parameters. AHI [women, 26.8 (interquartile
      range 13.9, 57.0) events per hour vs men, 58.9 (interquartile range 27.7, 105.7)
      events per hour, p<0.001] and AI/AHI ratio [women, 0.58 (0.36, 0.80) vs men, 0.80
      (0.51, 0.95), p<0.001) were higher in men compared to women. The independent
      predictors of the AHI were male gender, BMI, NC, and the %TST-supine. Independent
      predictors of the AI/AHI ratio were male gender, BMI, NC, and the percentage of
      time spent in the supine position. The increased AHI in men is secondary to an
      increased proportion of apneas in men compared to women and is independent of
      other potential determinants such as age, BMI, and NC.

PMID- 16283228
TI  - The effect of continuous positive airway pressure on glucose control in diabetic
      patients with severe obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is independently associated with glucose
      intolerance and insulin resistance, and recent studies have shown that continuous
      positive airway pressure (CPAP) improves insulin sensitivity. The objective of
      this study was to describe the change in glycosylated hemoglobin (HbA1c) after
      treatment with CPAP in patients with type 2 diabetes mellitus and OSA. To test
      this hypothesis, we performed a retrospective analysis of 38 patients seen in the
      sleep clinic of an urban public teaching hospital. All patients had OSA and type
      2 diabetes mellitus, and their diabetic medication regimen had remained unchanged
      during the period of CPAP therapy. Sixty-one percent were men, body mass index
      was 42+/-9.5 kg/m(2), and the Apnea-Hypopnea Index was 53+/-36 per hour. HbA1c
      before therapy with CPAP was 7.8+/-1.4% and decreased to 7.3+/-1.3% after 134+/
      119 days of therapy (p<0.001). Treatment with CPAP leads to a clinically
      significant drop in HbA1c in patients with type 2 diabetes mellitus and severe
      OSA.

PMID- 16283229
TI  - Effect of cardiac resynchronization therapy on sleep quality, quality of life,
      and symptomatic depression in patients with chronic heart failure and Cheyne
      Stokes respiration.
AB  - Patients with heart failure (HF) often suffer from sleep-related breathing
      disorders (SRBD) like Cheyne-Stokes respiration (CSR). Cardiac resynchronization
      therapy (CRT) improves myocardial function and exercise capacity in patients with
      HF and conduction disturbances. As CRT has been shown to reduce CSR in patients
      with HF, it is not clear whether CRT improves quality of life and symptomatic
      depression by improvement of apnea/hypopnea index (AHI) and sleep quality. Forty
      two HF patients with conduction disturbance before CRT were screened for CSR and
      evaluated for sleep quality [Pittsburgh Sleep Quality Index (PSQI)], quality of
      life score [36-item short form (SF-36)], depression, and exercise capacity (VO2
      peak) and ejection fraction (EF). Eighteen patients (three females, age 61+/-10,
      body mass index 24+/-4 kg m(-2), EF 24+/-4%, QRS complex duration 156+/-32 ms)
      presented CSR with an AHI of 18+/-8 (11 CSR, 7 mixed). Fourteen patients showed
      no SRBD (PSQI<5,AHI<5). All patients received CRT and were reevaluated after 18+/
      7 weeks. CSR worsen quality of life in seven of eight terms compared to patients
      without SRBD. Symptomatic depressive symptoms (Beck Depression Inventory>10) were
      only present in patients with CSR. CRT results in improvement of peak VO2 and EF.
      There was no difference between patients with CSR and without SRBD on exercise
      capacity or EF under CRT, whereas CRT led to a significant decrease in AHI (18+/
      8 to 3+/-2, p<0.0001), PSQI (18+/-4 to 6+/-3, p=0.0007), with reduction of
      depression score (12+/-3 to 4.8+/-3, p=0.004). In patients with HF, CSR is
      associated with symptomatic depressive syndromes and impaired quality of life.
      CRT reduced CSR with improvement of sleep quality and symptomatic depression.

PMID- 16283230
TI  - High-resolution mapping and mutation analysis separate the rust resistance genes
      Sr31, Lr26 and Yr9 on the short arm of rye chromosome 1.
AB  - The stem, leaf and stripe rust resistance genes Sr31, Lr26 and Yr9, located on
      the short arm of rye chromosome 1, have been widely used in wheat by means of
      wheat-rye translocation chromosomes. Previous studies have suggested that these
      resistance specificities are encoded by either closely-linked genes, or by a
      single gene capable of recognizing all three rust species. To investigate these
      issues, two 1BL.1RS wheat lines, one with and one without Sr31, Lr26 and Yr9,
      were used as parents for a high-resolution F2 mapping family. Thirty-six
      recombinants were identified between two PCR markers 2.3 cM apart that flanked
      the resistance locus. In one recombinant, Lr26 was separated from Sr31 and Yr9.
      Mutation studies recovered mutants that separated all three rust resistance
      genes. Thus, together, the recombination and mutation studies suggest that Sr31,
      Lr26 and Yr9 are separate closely-linked genes. An additional 16 DNA markers were
      mapped in this region. Multiple RFLP markers, identified using part of the barley
      Mla powdery mildew resistance gene as probe, co-segregated with Sr31 and Yr9. One
      deletion mutant that had lost Sr31, Lr26 and Yr9 retained all Mla markers,
      suggesting that the family of genes on 1RS identified by the Mla probe does not
      contain the Sr31, Lr26 or Yr9 genes. The genetic stocks and DNA markers generated
      from this study should facilitate the future cloning of Sr31, Lr26 and Yr9.

PMID- 16283231
TI  - Genetic relationships among South-East Turkey wild barley populations and
      sampling strategies of Hordeum spontaneum.
AB  - To assess the genetic diversity and the genetic structure of Turkish wild barley
      (Hordeum spontaneum Tell.) populations, 76 genotypes from ten ecologically and
      geographically different locations were analyzed by means of amplified fragment
      length polymorphism (AFLP) markers. Five primer combinations produced 187
      scorable bands, of which 117 (62.6%) were polymorphic. Several population
      specific and genotype-specific bands were identified, which differentiate
      populations or genotypes. Genetic distance, determined by Nei's distance
      coefficient, varied from 0.07 to 0.21 with an average of 0.13. In the UPGMA
      dendrogram based on Nei genetic distances, the Hordeum spontaneum populations
      were separated into two major clusters. Genetic diversity was larger among (68%)
      than within (32%) populations. Eight AFLP bands were strongly correlated to the
      altitude of the collecting site, while no clear trend was detected between
      geographical origin and genetic diversity. Our results strongly suggest the need
      for a change in Hordeum spontaneum sampling strategy: more populations, rather
      then more individuals within population, should be sampled to appraise and
      safeguard genetic diversity in the wild barley gene pool.

PMID- 16283232
TI  - Development of SCAR markers linked to three disease resistances based on AFLP
      within Nicotiana tabacum L.
AB  - Amplified fragment length polymorphism (AFLP) was conducted on a set of 92
      Nicotiana tabacum L. accessions from diverse types (flue-cured, dark air-cured,
      burley, oriental, and cigar wrapper) and breeding origins to identify markers
      associated with disease resistances. Eleven primer combinations were required to
      identify 33 polymorphic fragments. This allowed the identification of 92% of
      these accessions, and yielded sufficient information for building a neighbor
      joining tree. Clusters of accessions with common traits or breeding origins were
      observed. An important part of this polymorphism could be related to
      interspecific introgressions from other Nicotiana species, performed during the
      breeding history of N. tabacum to confer resistance to pathogens. Seven fragments
      were associated with three different resistances: two for the blue-mold
      (Peronospora tabacina Adam) resistance derived from Nicotiana debneyi Domin, two
      for the Va gene (Potato Virus Y susceptibility), and three for the black root rot
      (Chalara elegans) resistance of N. debneyi origin. Some of these markers were
      converted into sequence characterized amplified region markers, and validated on
      recombinant inbred lines or doubled-haploid lines.

PMID- 16283233
TI  - Characterization of low-molecular-weight glutenin subunit genes and their protein
      products in common wheats.
AB  - To characterize the low-molecular-weight glutenin subunit (LMW-GS), we developed
      specific PCR primer sets to distinguish 12 groups of LMW-GS genes of Norin 61 and
      to decide their loci with nullisomic-tetrasomic lines of Chinese Spring. Three,
      two, and ten groups were assigned to Glu-A3, Glu-B3, and Glu-D3 loci,
      respectively. To identify the proteins containing the corresponding amino acid
      sequences, we determined the N-terminal amino acid sequence of 12 spots of LMW
      GSs of Norin 61 separated by two-dimensional gel electrophoresis (2DE). The N
      terminal sequences of the LMW-GS spots showed that 10 of 12 groups of LMW-GSs
      were expressed as protein products, which included LMW-i, LMW-m, and LMW-s types.
      Four spots were encoded by Glu-A3 (LMW-i). Three spots were encoded by Glu-B3
      (LMW-m and LMW-s). Five spots were encoded by Glu-D3 (LMW-m and LMW-s). A minor
      spot of LMW-m seemed to be encoded by the same Glu-B3 gene as a major spot of LMW
      s, but processed at a different site. Comparing among various cultivars, there
      were polymorphic and non-polymorphic LMW-GSs. Glu-A3 was highly polymorphic,
      i.e., the a, b, and c alleles showed one spot, the d allele showed four spots,
      and the e allele had no spot. Insignia used as one of the Glu-A3 null standard
      cultivars had a LMW-GS encoded by Glu-A3. We also found that Cheyenne had a new
      Glu-D3 allele. Classification of LMW-GS by a combination of PCR and 2DE will be
      useful to identify individual LMW-GSs and to study their contribution to flour
      quality.

PMID- 16283234
TI  - Allele-specific CAPS markers based on point mutations in resistance alleles at
      the pvr1 locus encoding eIF4E in Capsicum.
AB  - Marker-assisted selection has been widely implemented in crop breeding and can be
      especially useful in cases where the traits of interest show recessive or
      polygenic inheritance and/or are difficult or impossible to select directly. Most
      indirect selection is based on DNA polymorphism linked to the target trait,
      resulting in error when the polymorphism recombines away from the mutation
      responsible for the trait and/or when the linkage between the mutation and the
      polymorphism is not conserved in all relevant genetic backgrounds. In this paper,
      we report the generation and use of molecular markers that define loci for
      selection using cleaved amplified polymorphic sequences (CAPS). These CAPS
      markers are based on nucleotide polymorphisms in the resistance gene that are
      perfectly correlated with disease resistance, the trait of interest. As a
      consequence, the possibility that the marker will not be linked to the trait in
      all backgrounds or that the marker will recombine away from the trait is
      eliminated. We have generated CAPS markers for three recessive viral resistance
      alleles used widely in pepper breeding, pvr1, pvr1 (1), and pvr1 (2). These
      markers are based on single nucleotide polymorphisms (SNPs) within the coding
      region of the pvr1 locus encoding an eIF4E homolog on chromosome 3. These three
      markers define a system of indirect selection for potyvirus resistance in
      Capsicum based on genomic sequence. We demonstrate the utility of this marker
      system using commercially significant germplasm representing two Capsicum
      species. Application of these markers to Capsicum improvement is discussed.

PMID- 16283235
TI  - Early growth and type 2 diabetes: evidence from the 1946 British birth cohort.
AB  - AIMS/HYPOTHESIS: We assessed whether low birthweight or early adiposity rebound
      was more strongly associated with type 2 diabetes, and whether any effect of low
      birthweight or early adiposity rebound was explained by adult BMI, adult height,
      social class of subject or of his/her father, or maternal or paternal diabetes.
      METHODS: Cox's proportional hazard models were used on data from the National
      Birth Cohort Study (the MRC National Survey of Health and Development), which was
      begun in 1946 and had self-reported physician-diagnosed diabetes with age at
      onset ranging from 31 to 53 years (n=78 cases, and n=47 cases in the multivariate
      analysis) as the outcome. RESULTS: A U-shaped association between birthweight and
      type 2 diabetes rates was close to statistical significance (quadratic term p
      value=0.08). Younger age at adiposity rebound was associated with increased rates
      of type 2 diabetes (test for trend p=0.002), the association being robust to
      adjustment for each of sex, birthweight, weight at 2 years, father's social
      class, parental diabetes, and own social class. The effect of early adiposity
      rebound was very slightly reduced by adjustment for sex and adult height
      (p=0.003), but considerably reduced after adjustment for sex and adult BMI (test
      for trend p=0.1), and further reduced (p=0.4) after additional adjustment for
      birthweight, weight at 2 years, adult height, social class of subject and of
      his/her father, and parental diabetes. CONCLUSIONS/INTERPRETATION: Early
      adiposity rebound was associated with an increased rate of type 2 diabetes
      independently of birthweight, but its effect was mostly through high adult BMI.
      Parental diabetes and possibly low weight at 2 years were also risks.

PMID- 16283236
TI  - Temporary hyperglycaemia provokes monocyte adhesion to endothelial cells in rat
      thoracic aorta.
AB  - AIMS/HYPOTHESIS: Several epidemiological data suggest that patients with
      postprandial hyperglycaemia are at high risk of cardiovascular disease. The aim
      of this study was to elucidate the effect of a glucose 'spike' on monocyte
      adhesion to rat aortic endothelial cells. MATERIALS AND METHODS: Monocyte
      adhesion to endothelial cells in vivo was quantitated using an en face method for
      observation of endothelial surface after immunohistochemical staining for CD68 in
      the thoracic aortas of Sprague-Dawley rats after several kinds of blood glucose
      rises. RESULTS: The number of monocytes adhering to endothelial cells increased
      at 30 min after injection of glucose in 8-week-old Sprague-Dawley rats. The
      increased adhesion returned to the basal level at 120 min after glucose
      injection, concomitantly with the return of blood glucose levels to normal. The
      infusion of octreotide to inhibit endogenous insulin secretion did not prevent
      the glucose-induced increase in monocyte adhesion to endothelial cells. On the
      other hand, the number of monocytes adhering to endothelial cells did not
      increase in rats with streptozotocin-induced diabetes and sustained
      hyperglycaemia. CONCLUSIONS/INTERPRETATION: Our data demonstrate that a temporary
      rise in blood glucose levels can in itself promote a reversible increase in
      monocyte adhesion to arterial endothelial cells.

PMID- 16283237
TI  - Extracellular signal-regulated kinase is essential for interleukin-1-induced and
      nuclear factor kappaB-mediated gene expression in insulin-producing INS-1E cells.
AB  - AIMS/HYPOTHESIS: The beta cell destruction and insulin deficiency that
      characterises type 1 diabetes mellitus is partially mediated by cytokines, such
      as IL-1beta, and by nitric oxide (NO)-dependent and -independent effector
      mechanisms. IL-1beta activates mitogen-activated protein kinases (MAPKs),
      including extracellular signal-regulated kinase (ERK), p38 and c-Jun NH2-terminal
      kinase (JNK), and the nuclear factor kappa B (NFkappaB) pathway. Both pathways
      are required for expression of the gene encoding inducible nitric oxide synthase
      (iNOS) and for IL-1beta-mediated beta cell death. The molecular mechanisms by
      which these two pathways regulate beta cell Nos2 expression are currently
      unknown. Therefore, the aim of this study was to clarify the putative crosstalk
      between MAPK and NFkappaB activation in beta cells. MATERIALS AND METHODS: The
      MAPKs ERK, p38 and JNK were inhibited by SB203580, PD98059 or Tat-JNK binding
      domain or by cells overexpressing the JNK binding domain. The effects of MAPK
      inhibition on IL-1beta-induced iNOS production and kappa B inhibitor protein
      (IkappaB) degradation were examined by western blotting. NFkappaB DNA binding was
      investigated by electrophoretic mobility shift assay, while NFkappaB-induced gene
      transcription was evaluated by gene reporter assays. RESULTS: Inhibition of the
      MAPKs did not affect IkappaB degradation or NFkappaB DNA binding. However,
      inhibition of ERK reduced NFkappaB-mediated Nos2 expression; serine 276
      phosphorylation of the p65 unit of the NFkappaB complex seemed critical, as
      evaluated by amino acid mutation analysis. CONCLUSIONS/INTERPRETATION: ERK
      activity is required for NFkappaB-mediated transcription of Nos2 in insulin
      producing INS-1E cells, indicating that ERK regulates Nos2 expression by
      increasing the transactivating capacity of NFkappaB. This may involve
      phosphorylation of Ser276 on p65 by an as yet unidentified kinase.

PMID- 16283238
TI  - Longitudinal changes in insulin sensitivity and secretion from birth to age three
      years in small- and appropriate-for-gestational-age children.
AB  - AIMS/HYPOTHESIS: Insulin resistance and type 2 diabetes risk in human subjects
      who were small-for-gestational-age (SGA) at birth may be a consequence of rapid
      early postnatal weight gain. MATERIALS AND METHODS: We prospectively studied
      early changes in fasting insulin sensitivity and insulin secretion, assessed by a
      short intravenous glucose tolerance test that was conducted several times from
      birth to 3 years of age in 55 SGA (birthweight below fifth percentile) newborns
      and in 13 newborns with a birthweight appropriate for gestational age (AGA).
      RESULTS: Most SGA infants showed postnatal upward weight centile crossing and by
      3 years were similar in size to AGA infants. SGA infants had lower pre-feed
      insulin levels at postnatal age 48 h than AGA infants (median 34.4 vs 59.7
      pmol/l, p<0.05), but by the age of 3 years they had higher fasting insulin levels
      (median 38.9 vs 23.8 pmol/l, p<0.005), which were related to rate of weight gain
      between 0 and 3 years (r=0.47, p=0.0003). First-phase insulin secretion did not
      differ between SGA and AGA infants, but SGA infants had a lower glucose
      disposition index (beta cell compensation) (median 235 vs 501 min mmol(-1) l(-1),
      p=0.02), which persisted after allowing for postnatal weight gain (p=0.009).
      CONCLUSIONS/INTERPRETATION: SGA infants showed a marked transition from lower pre
      feed insulin and increased insulin sensitivity at birth to insulin resistance
      over the first 3 years of life. This transition was related to rapid postnatal
      weight gain, which could indicate a propensity to central fat deposition. The
      additional observation of reduced compensatory beta cell secretion underlines the
      need for long-term surveillance of glucose homeostasis in all SGA subjects,
      whether or not they show postnatal catch-up growth.

PMID- 16283239
TI  - Long-term effects on lipids and lipoproteins of pioglitazone versus gliclazide
      addition to metformin and pioglitazone versus metformin addition to sulphonylurea
      in the treatment of type 2 diabetes.
AB  - AIMS/HYPOTHESIS: The aim of this study was to determine the long-term effects of
      pioglitazone add-on to metformin or sulphonylurea on plasma lipids and
      lipoproteins. MATERIALS AND METHODS: The effects of pioglitazone were studied in
      two clinical trials in patients with inadequately controlled type 2 diabetes
      (HbA1c > or =7.5 and < or =11%). In the first trial, patients currently receiving
      metformin were randomised to pioglitazone (15-45 mg/day, n=317) or gliclazide (80
      320 mg/day, n=313) add-on therapy. In the second study, pioglitazone (15-45
      mg/day, n=319) or metformin (850-2,550 mg/day, n=320) was added to sulphonylurea
      therapy. Patients were force-titrated to the maximum tolerated dose of add-on
      therapy, which was maintained to the 2-year endpoint. RESULTS: There were no
      statistically significant differences between the groups with respect to HbA1c
      reduction from baseline to week 104. Whether added to metformin or sulphonylurea,
      pioglitazone caused highly significant greater decreases in triglycerides and
      increases in HDL cholesterol from baseline to week 104 than treatments with
      gliclazide or metformin add-on therapies (p< or =0.001). The triglyceride
      reductions noted with pioglitazone were maintained over time, with decreases of
      16-18% at 1 year and 17-23% at 2 years. In the pioglitazone groups, the
      improvement in HDL cholesterol at 1 year was maintained, with 21-22%
      augmentations at 2 years (p<0.001 between-group difference). Small but
      statistically significant greater reductions in LDL cholesterol were observed
      with gliclazide vs pioglitazone add-on to metformin and metformin vs pioglitazone
      add-on to sulphonylurea (p<0.001 for between-group difference). In the
      pioglitazone groups, mean LDL cholesterol at 2 years was similar to mean baseline
      LDL cholesterol. CONCLUSIONS/INTERPRETATION: After 2 years, highly significant
      decreases in triglycerides and increases in HDL cholesterol that were sustained
      over time or even improved were observed when pioglitazone was added to metformin
      or sulphonylurea therapy. These effects of pioglitazone on lipids may be
      potentially beneficial in reducing cardiovascular risk in type 2 diabetes.

PMID- 16283240
TI  - The 'accelerator hypothesis': relationship between weight, height, body mass
      index and age at diagnosis in a large cohort of 9,248 German and Austrian
      children with type 1 diabetes mellitus.
AB  - AIMS/HYPOTHESIS: The aim of this study was to investigate whether either
      increased weight or BMI are associated with the earlier manifestation of type 1
      diabetes mellitus in children. METHODS: We evaluated anthropometric measurements
      in a large cohort of 9,248 patients of European extraction who were diagnosed in
      the years 1990-2003 in 116 pediatric clinics throughout Germany and Austria.
      RESULTS: Patients were divided into four groups according to age (0-4.9 years, 5
      9.9 years, 10-14.9 years and 15-20 years). Significantly higher standard
      deviation scores (SDSs) for weight and BMI at diabetes onset were found for both
      boys and girls in the three younger age groups (up to 14.9 years of age) compared
      with the reference population (p<0.00001). In addition, the BMI SDS and the
      weight SDS were significantly higher in the 0-4.9-years age group than in all
      other groups (p<0.00001), and BMI SDS at onset gradually decreased with
      increasing age at manifestation (p<0.0001). Over the >10-year study period, there
      was a continuous rise in the weight-SDS and the BMI-SDS in the cohort (p<0.0001),
      especially in the 5-9.9-years and the 10-14.9-years age groups. Multivariate
      analysis revealed a significant influence of male sex and of year of
      manifestation on BMI SDS (p<0.0001) and demonstrated a negative association
      between the patients' BMI SDS and age at diagnosis, with a mean annual decrease
      in BMI SDS of -0.0248 (95% CI -0.0294 to -0.0202, p<0.0001).
      CONCLUSIONS/INTERPRETATION: A higher BMI was associated with a younger age at
      diabetes onset. Increased weight gain could therefore be a risk factor for the
      early manifestation of type 1 diabetes.

PMID- 16283241
TI  - Fine-tuning insulin and nitric oxide signalling by turning up the AMPs: new
      insights into AMP-activated protein kinase signalling.

PMID- 16283243
TI  - Selective loss of glucose-induced amplification of insulin secretion in mouse
      pancreatic islets pretreated with sulfonylurea in the absence of fuels.
AB  - AIMS/HYPOTHESIS: The beta cell metabolism of glucose, and some other fuels,
      initiates insulin secretion by closure of ATP-sensitive K+ channels and amplifies
      the secretory response via unknown metabolic intermediates. The aim of this study
      was to further characterise the mechanism responsible for the metabolic
      amplification of insulin secretion. MATERIALS AND METHODS: Pancreatic islets were
      isolated from albino mice by collagenase digestion. Insulin secretion in
      perifused islets was determined by ELISA. Bioluminometry was used to determine
      the ATP and ADP content of the incubated islets. RESULTS: After perifusing islets
      for 60 min with 2.7 micromol/l glipizide (closing all ATP-sensitive K+ channels)
      in the absence of any fuel, perifusion with a test medium containing 2.7
      micromol/l glipizide plus 30 mmol/l glucose did not enhance insulin secretion.
      However, test media supplemented with 2.7 micromol/l glipizide plus either 10
      mmol/l alpha-ketoisocaproate or 10 mmol/l 2-aminobicyclo[2,2,1]heptane-2
      carboxylic acid amplified the glipizide-induced insulin secretion. In pancreatic
      islets preincubated for 60 min with 2.7 micromol/l glipizide in the absence of
      any fuel, 40 min incubations in the presence of 2.7 micromol/l glipizide plus 30
      mmol/l glucose or plus 10 mmol/l alpha-ketoisocaproate produced an increase in
      the ATP content, no change in the ADP content and a rather small increase in the
      ATP:ADP ratio. The corresponding effects of glucose and alpha-ketoisocaproate
      were similar. CONCLUSIONS/INTERPRETATION: These results suggest that metabolic
      amplification of fuel-induced insulin secretion is not mediated by changes in the
      beta cell content of ATP and ADP, but might be due to export of citrate cycle
      intermediates to the beta cell cytosol.

PMID- 16283242
TI  - Essential role of the imidazoline moiety in the insulinotropic effect but not the
      KATP channel-blocking effect of imidazolines; a comparison of the effects of
      efaroxan and its imidazole analogue, KU14R.
AB  - AIMS/HYPOTHESIS: Imidazolines are a class of investigational antidiabetic drugs.
      It is still unclear whether the imidazoline ring is decisive for insulinotropic
      characteristics. MATERIALS AND METHODS: We studied the imidazoline efaroxan and
      its imidazole analogue, KU14R, which is currently classified as an imidazoline
      antagonist. The effects of both on stimulus secretion-coupling in normal mouse
      islets and beta cells were compared by measuring KATP channel activity, plasma
      membrane potential, cytosolic calcium concentration ([Ca2+]c) and dynamic insulin
      secretion. RESULTS: In the presence of 10 mmol/l but not of 5 mmol/l glucose,
      efaroxan (100 micromol/l) strongly enhanced insulin secretion by freshly isolated
      perifused islets, whereas KU14R (30, 100 or 300 micromol/l) was ineffective at
      both glucose concentrations. Surprisingly, the insulinotropic effect of efaroxan
      was not antagonised by KU14R. KATP channels were blocked by efaroxan (IC50 8.8
      micromol/l, Hill slope -1.1) and by KU14R (IC50 31.9 micromol/l, Hill slope 
      1.5). Neither the KATP channel-blocking effect nor the depolarising effect of
      efaroxan was antagonised by KU14R. Rather, both compounds strongly depolarised
      the beta cell membrane potential and induced action potential spiking. However,
      KU14R was clearly less efficient than efaroxan in raising [Ca2+]c in single beta
      cells and whole islets at 5 mmol/l glucose. The increase in [Ca2+]c induced by 10
      mmol/l glucose was affected neither by efaroxan nor by KU14R. Again, KU14R did
      not antagonise the effects of efaroxan. CONCLUSIONS/INTERPRETATION: The presence
      of an imidazole instead of an imidazoline ring leads to virtually complete loss
      of the insulinotropic effect in spite of a preserved ability to block KATP
      channels. The imidazole compound is less efficient in raising [Ca2+]c; in
      particular, it lacks the ability of the imidazoline to potentiate the enhancing
      effect of energy metabolism on Ca2+-induced insulin secretion.

PMID- 16283244
TI  - Spring harvest? Reflections on the rise of type 1 diabetes.

PMID- 16283245
TI  - Contraindications can damage your health--is metformin a case in point?
AB  - Metformin is an effective anti-hyperglycaemic and cardioprotective agent, but a
      long list of contraindications precludes millions of patients with type 2
      diabetes from using it. This is largely due to the historical experience of
      lactic acidosis with phenformin, despite the fact that metformin does not
      predispose to this when compared with other therapies. Contraindications such as
      old age, renal impairment and cardiac insufficiency are increasingly disregarded
      in clinical practice, yet there is no evidence that the incidence of lactic
      acidosis has changed. Metformin has been shown to improve metabolic control
      without causing lactic acidosis in elderly patients with multiple comorbidities,
      including explicit contraindications, and its use in patients with type 2
      diabetes over the age of 70 with mild renal impairment did not produce a
      clinically relevant increase in plasma lactate. There is no correlation between
      levels of metformin and lactate in patients with lactic acidosis, and its
      prognosis is mainly related to the causal hypoxic underlying disease and
      comorbidities. These findings raise doubts about the pathogenetic significance of
      metformin in lactic acidosis. We propose that advanced age per se, mild renal
      impairment and compensated heart failure can no longer be upheld as
      contraindications for metformin. A clear re-definition of contraindications to
      metformin will enable more physicians to prescribe within guidelines.

PMID- 16283246
TI  - Cognitive decline and dementia in diabetes--systematic overview of prospective
      observational studies.
AB  - AIMS/HYPOTHESIS: We systematically reviewed and summarised prospective data
      relating diabetes status to changes in cognitive function over time. METHODS:
      Published reports of longitudinal studies that described assessment of cognitive
      function in people with diabetes were sought. Studies were included if they
      assessed cognitive function in participants with diabetes at the beginning and at
      follow-up. Studies were excluded if they had (1) a follow-up period of less than
      1 year, (2) a rate of loss to follow-up in excess of 30%, or (3) described
      selected subgroups. Change in cognitive function was recorded as either the mean
      change in score and/or the proportion of individuals developing various degrees
      of change in cognitive function. A pooled estimate was calculated for the latter.
      RESULTS: Of 1,165 abstracts and titles initially identified, 25 articles met the
      inclusion and exclusion criteria. Individuals with diabetes had a 1.2- to 1.5
      fold greater change over time in measures of cognitive function than those
      without diabetes. When assessed by the Mini-Mental State Exam and the Digit
      Symbol Span tests, a diagnosis of diabetes increased the odds of cognitive
      decline 1.2-fold (95% CI 1.05-1.4) and 1.7-fold (95% CI 1.3-2.3), respectively .
      The odds of future dementia increased 1.6-fold (95% CI 1.4-1.8).
      CONCLUSIONS/INTERPRETATION: Compared to people without diabetes, people with
      diabetes have a greater rate of decline in cognitive function and a greater risk
      of cognitive decline. Cognitive dysfunction should therefore be added to the list
      of chronic complications of diabetes.

PMID- 16283247
TI  - Weight gain in relation to plasma levels of complement factor 3: results from a
      population-based cohort study.
AB  - AIMS/HYPOTHESIS: Mice that are deficient for complement factor 3 (C3) have shown
      resistance to weight gain, despite increased food intake. Cross-sectional studies
      of humans have reported correlations between C3 and obesity. This longitudinal
      study explored whether C3 predicts a large weight gain in middle-aged men.
      METHODS: Plasma concentrations of C3 and complement factor 4 (C4) were measured
      in 2,706 non-diabetic healthy men aged between 38 and 50 years, who were re
      examined after a mean period of 6.1 years. RESULTS: After adjustments for initial
      weight, age, height and follow-up time, the odds of incurring large weight gain
      (75th percentile, > or =3.8 kg) were 1.00 (reference), 0.96 (95% CI:0.7-1.2), 1.1
      (CI:0.9-1.5) and 1.4 (CI:1.1-1.8), respectively, among men with C3 levels in the
      first, second, third and fourth quartiles (p for trend=0.01) respectively. This
      relationship remained significant after further adjustments for lifestyle factors
      (physical inactivity, alcohol, smoking), metabolic factors (glucose or
      homeostasis model assessment values, cholesterol, triglycerides), inflammatory
      markers (fibrinogen, haptoglobin, ceruloplasmin, orosomucoid, alpha1-antitrypsin)
      and for C4. C4 was associated with weight gain after adjustments for initial
      weight, height, follow-up time and lifestyle factors, but not after adjustments
      for C3. CONCLUSIONS/INTERPRETATION: C3 is a risk factor for incurring large
      weight gain in middle-aged men.

PMID- 16283250
TI  - Isolation of constitutive variants of a subfamily 10 histidine protein kinase
      (SppK) from Lactobacillus using random mutagenesis.
AB  - The histidine protein kinase SppK is a peptide pheromone-activated kinase that
      regulates the production of the bacteriocin sakacin P in Lactobacillus sakei.
      SppK belongs to subfamily 10 of histidine protein kinases (HPKs), which regulate
      important processes in Gram-positive bacteria, including virulence, competence
      and bacteriocin production. To obtain insight into the functional properties of
      this relatively unknown class of HPKs, we have subjected SppK to random
      mutagenesis by error-prone PCR, followed by selection for mutants displaying a
      constitutive phenotype. Most identified mutations were clustered in a predicted
      coiled coil-like region, which is an important part of the HPK dimer interface
      and which includes the autophosphorylated histidine. Other mutations were located
      in the junctions between the dimerization domain and the membrane receptor domain
      or the catalytic kinase domain. Interestingly, two previously identified
      constitutive variants of ComD, an SppK homologue involved in competence
      regulation in Streptococcus pneumoniae, contained single mutations in the same
      regions.

PMID- 16283249
TI  - Increased expression of advanced glycation end-products and their receptor, and
      activation of nuclear factor kappa-B in lacrimal glands of diabetic rats.
AB  - AIMS/HYPOTHESIS: To assess the involvement of the AGE-specific receptor (AGER,
      also known as RAGE) axis and nuclear factor kappa-B (NFKB, also known as NF
      kappaB) activation in the development of lacrimal gland and tear film dysfunction
      in diabetes, the present study evaluated: (1) lacrimal gland and tear film
      alterations in diabetic rats; and (2) the expression of AGE, AGER and NFKB in
      ocular tissues of normoglycaemic and diabetic rats. MATERIALS AND METHODS:
      Diabetes was induced in male Wistar rats with intravenous streptozotocin. Tear
      secretion parameters were measured and NFKB expression was evaluated in lacrimal
      glands of control and diabetic rats by western blot. Immunohistochemistry with
      confocal microscopy was used to assess AGE, AGER and NFKB expression in lacrimal
      glands of both groups. RESULTS: Lacrimal gland weight and tear film volume were
      lower in diabetic than in control rats (p=0.01 and 0.02, respectively). IL1B and
      TNF concentrations in tears were higher in diabetic than in control rats (p=0.007
      and 0.02, respectively). NFKB protein was identified in rat cornea, conjunctiva
      and lacrimal glands. AGE, AGER and NFKB expression were greater in lacrimal
      glands of diabetic than in those of control rats. CONCLUSIONS/INTERPRETATION:
      Diabetes induces significant alterations in rat lacrimal gland structure and
      secretion. The higher expression of AGE, AGER and NFKB in lacrimal glands of
      diabetic rats suggests that these factors are involved in signalling and in
      subsequent inflammatory alterations related to dry eye in diabetes mellitus.

PMID- 16283248
TI  - Insulin signalling downstream of protein kinase B is potentiated by 5'AMP
      activated protein kinase in rat hearts in vivo.
AB  - AIMS/HYPOTHESIS: 5'AMP-activated protein kinase (AMPK) and insulin stimulate
      glucose transport in heart and muscle. AMPK acts in an additive manner with
      insulin to increase glucose uptake, thereby suggesting that AMPK activation may
      be a useful strategy for ameliorating glucose uptake, especially in cases of
      insulin resistance. In order to characterise interactions between the insulin-
      and AMPK-signalling pathways, we investigated the effects of AMPK activation on
      insulin signalling in the rat heart in vivo. METHODS: Male rats (350-400 g) were
      injected with 1 g/kg 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside
      (AICAR) or 250 mg/kg metformin in order to activate AMPK. Rats were administered
      insulin 30 min later and after another 30 min their hearts were removed. The
      activities and phosphorylation levels of components of the insulin-signalling
      pathway were subsequently analysed in individual rat hearts. RESULTS: AICAR and
      metformin administration activated AMPK and enhanced insulin signalling
      downstream of protein kinase B in rat hearts in vivo. Insulin-induced
      phosphorylation of glycogen synthase kinase 3 (GSK3) beta, p70 S6 kinase
      (p70S6K)(Thr389) and IRS1(Ser636/639) were significantly increased following AMPK
      activation. To the best of our knowledge, this is the first report of heightened
      insulin responses of GSK3beta and p70S6K following AMPK activation. In addition,
      we found that AMPK inhibits insulin stimulation of IRS1-associated
      phosphatidylinositol 3-kinase activity, and that AMPK activates atypical protein
      kinase C and extracellular signal-regulated kinase in the heart.
      CONCLUSIONS/INTERPRETATIONS: Our data are indicative of differential effects of
      AMPK on the activation of components in the cardiac insulin-signalling pathway.
      These intriguing observations are critical for characterisation of the crosstalk
      between AMPK and insulin signalling.

PMID- 16283251
TI  - Characterization of the ectoine biosynthesis genes of haloalkalotolerant obligate
      methanotroph "Methylomicrobium alcaliphilum 20Z".
AB  - The genes involved in biosynthesis of the major compatible solute ectoine
      (1,4,5,6-tetrahydro-2-methylpyrimidine carboxylic acid) in halotolerant obligate
      methanotroph "Methylomicrobium alcaliphilum 20Z" were studied. The complete
      nucleotide sequences of the structural genes encoding L: -aspartokinase (Ask), L
      2,4-diaminobutyric acid transaminase (EctB), L-2,4-diaminobutyric acid
      acetyltransferase (EctA), and L-ectoine synthase (EctC) were defined and shown to
      be transcribed as a single operon ectABCask. Phylogenetic analysis revealed high
      sequence identities (34-63%) of the Ect proteins to those from halophilic
      heterotrophs with the highest amino acid identities being to Vibrio cholerae
      enzymes. The chromosomal DNA fragment from "M. alcaliphilum 20Z" containing
      ectABC genes and putative promoter region was expressed in Escherichia coli.
      Recombinant cells could grow in the presence of 4% NaCl and synthesize ectoine.
      The data obtained suggested that despite the ectoine biosynthesis pathway being
      evolutionary well conserved with respect to the genes and enzymes involved, some
      differences in their organization and regulation could occur in various
      halophilic bacteria.

PMID- 16283252
TI  - Transformation of metals and metal ions by hydrogenases from phototrophic
      bacteria.
AB  - The ability of hydrogenases isolated from Thiocapsa roseopersicina and
      Lamprobacter modestohalophilus to reduce metal ions and oxidize metals has been
      studied. Hydrogenases from both phototrophic bacteria oxidized metallic Fe, Cd,
      Zn and Ni into their ionic forms with simultaneous evolution of molecular
      hydrogen. The metal oxidation rate decreased in the series Zn > Fe > Cd > Ni and
      depended on the pH. The presence of methyl viologen in the reaction system
      accelerated this process. T. roseopersicina and L. modestohalophilus cells and
      their hydrogenases reduced Ni(II), Pt(IV), Pd(II) or Ru(III) to their metallic
      forms under H2 atmosphere. These results suggest that metals or metal ions can
      serve as electron donors or acceptors for hydrogenases from phototrophic
      bacteria.

PMID- 16283253
TI  - Partial purification and characterization of a novel neurotoxin and three
      cytolysins from box jellyfish (Carybdea marsupialis) nematocyst venom.
AB  - This paper describes one neurotoxin and three cytolysins isolated from the venom
      of the Caribbean box jellyfish Carybdea marsupialis. To assess the cytolytic and
      neurotoxic activity of the nematocyst venom, several bioassays were carried out,
      and to evaluate the effect of the toxin, the dose causing 50% lethality (LD(50))
      was determined in vivo using sea crabs (Ocypode quadrata). The proteins with
      neurotoxic and cytolytic effects were isolated using low-pressure liquid
      chromatography. The fraction containing the neurotoxic activity was analyzed by
      SDS-PAGE and showed a single protein band with an apparent molecular weight of
      120 kDa (CmNt). To demonstrate the neurotoxic activity of this protein, a small
      fraction of the purified protein was injected into a crab, and the typical
      convulsions, paralysis, and death provoked by neurotoxins were observed. Three
      fractions containing cytolysins had protein bands in SDS PAGE with apparent
      molecular weights of 220, 139, and 36 kDa, and their cytolytic activity was
      confirmed with the haemolysis assay.

PMID- 16283255
TI  - Effects of the local administration of selective mu-, delta-and kappa-opioid
      receptor agonists on osteosarcoma-induced hyperalgesia.
AB  - The stimulation of peripheral opioid receptors yields analgesic responses in a
      model of bone cancer-induced pain in mice. In order to know the type(s) of
      peripheral opiate receptors involved, the paw thermal withdrawal latencies were
      measured in C3H/HeJ mice bearing a tibial osteosarcoma, after administering
      selective agonists of mu-,delta-and kappa-opiate receptors. The peritumoral
      administration of DAGO (0.6-6 microg) inhibited the osteosarcoma-induced
      hyperalgesia at doses ineffective in healthy animals, the highest one even
      increasing the withdrawal latencies over the control values. Naloxone-methiodide
      (2 mg/kg) and cyprodime (1 mg/kg), but not naltrindole (0.1 mg/kg) nor nor
      binaltorphimine (10 mg/kg), antagonized DAGO-induced analgesic effects, these
      therefore probably being mediated through peripheral mu-opioid receptors. The
      peritumoral injection of DPDPE (100 microg) induced analgesia which was inhibited
      by naloxone-methiodide and naltrindole but not by nor-binaltorphimine. Cyprodime
      partially antagonized the analgesia induced by 100 microg of DPDPE, but did not
      modify the effect induced by 30 microg of this agonist-a dose that restores the
      hyperalgesic latencies up to the control values. The antihyperalgesic effect
      induced by the peritumoral administration of U-50,488H (1 microg) was antagonized
      by naloxone-methiodide and nor-binaltorphimine, but not by cyprodime nor
      naltrindole, thus suggesting the involvement of peripheral kappa-opioid
      receptors. In conclusion, the stimulation of peripheral mu-, delta- and kappa
      opioid receptors is a pharmacological strategy useful for relieving this
      experimental type of bone cancer-induced pain, the greatest analgesic effect
      being achieved by stimulating peripheral mu-opioid receptors.

PMID- 16283254
TI  - Effect of rilmakalim on detrusor contraction in the presence and absence of
      urothelium.
AB  - Openers of K(ATP) channels are known to inhibit KCl-, carbachol- and also
      electrically induced contractions in detrusor muscle strips from various species.
      Contractions of isolated strips of urinary bladder are usually of higher
      amplitude when the urothelium has been removed. This has been explained by the
      release of an urothelium-derived relaxing factor. In this study we examined
      whether intact urothelium may modulate the effect of the selective KATP channel
      opener rilmakalim. Contractile responses to 85 mM KCl and 10 microM carbachol
      were measured in detrusor strips from mouse, pig and man. In the presence of an
      intact urothelium, contractions were significantly reduced in strips from all
      three species investigated. In preparations with urothelium rilmakalim reduced
      KCl contractions with similar potency and efficacy [-logIC50 (M) 4.6 to 5.1;
      Effmax reduction to 14-30% of control]. However, in urothelium-denuded strips
      rilmakalim was more potent in pig (-logIC50 5.5) than in mouse and man (-logIC50
      4.7 and 4.4, respectively). The order of potency for rilmakalim to suppress
      carbachol-induced contractions was pig (-logIC50 6.7)>man (5.8)>mouse (4.7);
      contractions were significantly more reduced in pig (Effmax reduction to 11+/-2%,
      n=10) and in mouse (21+/-2%, n=8) than in human detrusor (55+/-5%, n=5). The
      presence of urothelium did not affect the concentration-response curves for
      rilmakalim, with the exception of KCl-induced contractions in pig. Only the
      rilmakalim-induced relaxation of carbachol-mediated contractions in pig were
      prevented by the KATP channel blocker glibenclamide. We conclude that with this
      one exception, the responses to rilmakalim in detrusor contractions were not
      mediated by KATP channel opening.

PMID- 16283256
TI  - Population pharmacokinetic analysis of drug-drug interactions among risperidone,
      bupropion, and sertraline in CF1 mice.
AB  - RATIONALE: Accumulating evidence indicates that modulation of the activity of
      cytochrome P450 (CYP) enzymes and the multidrug resistance transporter P
      glycoprotein (P-gp) is responsible for many drug-drug interactions. OBJECTIVES:
      The potential interaction of risperidone (RISP), which is metabolized by 2D6 and
      transported across the blood brain barrier (BBB) by P-gp, was studied in
      combination with bupropion (BUP) and also with sertraline (SERT). METHODS: BUP,
      SERT, and RISP were administered intraperitoneally into CF1 mice at doses of 100,
      10, and 1 microg/g mouse, respectively. Plasma and brain samples were collected
      at timed intervals from 0.5 to 6 h. A pharmacokinetic analysis was performed
      using both traditional compartmental modeling and a population pharmacokinetic
      approach. RESULTS: BUP increased the RISP plasma (5.9-fold, P<0.01) and brain
      (2.2-fold, P<0.01) area under the drug concentration vs time curve (AUC), but did
      not alter the brain-to-plasma concentration ratio. SERT did not significantly
      change the plasma AUC of RISP and 9-hydroxy-RISP, but increased the brain AUC of
      RISP and 9-hydroxy-RISP 1.5-fold (P<0.05) and 5-fold (P<0.01), respectively. RISP
      did not produce significant alterations of plasma or brain concentrations of BUP.
      It increased the plasma AUC and elimination half-life (T1/2e) of desmethyl-SERT
      12.5-fold (P<0.01) and 107-fold (P<0.01), respectively. CONCLUSIONS: These
      results suggest that pharmacokinetic interactions exist among these three
      psychoactive drugs involving inhibition of drug metabolizing enzymes and/or P-gp
      and other drug transporters present in the BBB. The mechanisms and consequences
      of these interactions require further study in humans to establish clinical
      relevance.

PMID- 16283257
TI  - Diisopropylfluorophosphate administration in the pre-weanling period induces long
      term changes in anxiety behavior and passive avoidance in adult mice.
AB  - The developing brain may be particularly vulnerable to exposure to
      acetylcholinesterase (AChE) inhibitors because of the role of AChE on neuronal
      development and the effects of cholinergic pathways in mediating behavioral and
      hormonal responses to stress. C57BL/65 mice of both sexes were injected with 1
      mg/kg s.c. diisopropylfluorophosphate (DFP) or saline in three separate
      experiments, on postnatal days (PNDs) 4-10, 14-20, or 30-36. Anxiety and
      conditioned avoidance were assessed on the elevated-plus maze (EPM) and step-down
      passive avoidance (PA) paradigms, respectively, at age 4-5 months. In addition,
      locomotion and reactivity to pain on the hot plate were assessed. Mice treated on
      PNDs 4-10 or PNDs 14-20 spent relatively more time and made more entries to the
      open arms on the first, but not second, exposure to the EPM. Females, but not
      males, treated with DFP showed deficits in PA retention after 24 h when treated
      on PNDs 4-10 and on PNDs 14-20. Mice treated on PNDs 30-36 were not impaired in
      either behavior. Administration of DFP in the preweanling period did not affect
      locomotor activity or pain reactivity. The results suggest that preweanling
      exposure to DFP results in anxiolysis in novel conflict situations but
      exacerbated context-enhanced anxiety.

PMID- 16283259
TI  - Bacillus anthracis: toxicology, epidemiology and current rapid-detection methods.
AB  - B. anthracis, the causative agent for anthrax, has been well studied for over 150
      years. Due to the genetic similarities among various Bacillus species, as well as
      its existence in both a spore form and a vegetative state, the detection and
      specific identification of B. anthracis have been proven to require complex
      techniques and/or laborious methods. With the heightened interest in the organism
      as a potential biological threat agent, a large number of interesting detection
      technologies have recently been developed, including methods involving
      immunological and nucleic acid-based assay formats. The technologies range from
      culture-based methods to portable Total Analysis Systems based on real-time PCR.
      This review with 170 references provides a brief background on the toxicology and
      epidemiology of B. anthracis, discusses challenges associated with its detection
      related to genetic similarities to other species, and reviews immunological and,
      with greater emphasis, nucleic acid-based detection systems.

PMID- 16283258
TI  - Immediate hedonic response to smoking lapses: relationship to smoking relapse,
      and effects of nicotine replacement therapy.
AB  - OBJECTIVE AND RATIONALE: Smoking lapses represent an important juncture between
      smoking cessation and relapse. Nicotine replacement therapy (NRT) has been shown
      to decrease the risk of progression from lapse to relapse. We hypothesized that
      this effect might be mediated via decreases in reinforcement from smoking lapses.
      METHOD: We assessed 169 subjects who lapsed during treatment in a double-blind
      placebo-controlled study of high-dose (35 mg) nicotine patch. Following their
      first lapse, using an electronic diary, subjects recorded the amount they smoked,
      and rated the pleasantness and satisfaction ("hedonic rating") and the
      aversiveness of smoking. Subjects were then followed and assessed for further
      lapses and relapses. RESULTS: Subjects who smoked more during the first lapse had
      greater risk of progression [second lapse: hazard ratio (HR)=1.16, confidence
      interval (CI)=1.01-1.32; relapse: HR=1.22, CI=0.97-1.54]. Subjects with higher
      hedonic ratings of the first lapse also had a greater risk of progression to the
      second lapse (HR=1.08, CI=1.02-1.14) and to relapse (HR=1.26, CI=1.11-1.41).
      Aversive ratings had no bearing on progression. As expected, active treatment
      reduced the risk of both a second lapse (HR=0.54, CI=0.39-0.78) and a relapse
      (HR=0.22, CI=0.11-0.45). Importantly, however, NRT had no effect on hedonic
      ratings, amount smoked during the first lapse, or aversive ratings. CONCLUSIONS:
      Hedonic response to an initial lapse predicted progression to relapse, but this
      did not mediate the effect of NRT on progression.

PMID- 16283260
TI  - Automated high-throughput nanoliter-scale protein crystallization screening.
AB  - A highly efficient method is developed for automated high-throughput screening of
      nanoliter-scale protein crystallization. The system integrates liquid dispensing,
      crystallization and detection. The automated liquid dispensing system handles
      nanoliters of protein and various combinations of precipitants in parallel to
      access diverse regions of the phase diagram. A new detection scheme, native
      fluorescence, with complementary visible-light detection is employed for
      monitoring the progress of crystallization. This detection mode can distinguish
      protein crystals from inorganic crystals in a nondestructive manner. A gas
      permeable membrane covering the microwells simplifies evaporation rate control
      and probes extended conditions in the phase diagram. The system was successfully
      demonstrated for the screening of lysozyme crystallization under 81 different
      conditions.

PMID- 16283261
TI  - Enhancement of enzymatic digestion of Antarctic krill and successive extraction
      of selenium organic compounds by ultrasound treatment.
AB  - In a previous work we described the isolation of selenium organic species from
      Antarctic krill after enzymatic hydrolysis. In this paper we present the results
      of the influence of ultrasonication on the enzymatic treatment and the successive
      isolation of selenomethionine. We showed that ultrasound-assisted enzymatic
      digestion leads to quantitative release of selenium in the soluble fraction and
      recovery of selenomethionine from the krill protein within a time 2 orders of
      magnitude shorter. The solubilised sample was analysed by size-exclusion
      chromatography and the selenomethionine content was quantified by high
      performance liquid chromatography-inductively coupled plasma mass spectrometry.
      In total, 99% of the selenomethionine in the krill hydrolysate was recovered from
      the chromatographic fractions. It corresponds to 35% of the total selenium
      content in Antarctic krill. Monitoring by microscopy of the changes in the
      structure of the krill samples during ultrasonication suggested that the
      enhancement of the ultrasound-assisted enzymatic reaction was mainly due to
      decrease of mass transfer limitations. A reference experiment for ultrasound
      assisted enzymatic digestion of cell-free protein in a homogeneous system does
      not exclude direct influence of the ultrasound energy on the enzyme-substrate
      interaction.

PMID- 16283263
TI  - Colloquium analytical atomic spectroscopy.

PMID- 16283262
TI  - Establishing a chromium-reactor design for measuring delta2H values of solid
      polyhalogenated compounds using direct elemental analysis and stable isotope
      ratio mass spectrometry.
AB  - 2H/1H isotope ratios of polyhalogenated compounds were determined by elemental
      analysis and isotope ratio mass spectrometry (EA-IRMS). Initial measurements with
      standard EA-IRMS equipment, which used high-temperature pyrolysis to convert the
      organic compounds into hydrogen, did not achieve significant signals for
      polychlorinated pesticides and related compounds, presumably due to the formation
      of HCl instead of hydrogen. To reverse this problematic reaction, a chromium
      reactor was incorporated into the element analyzer system, which scavenged Cl,
      forming chromium chloride and releasing hydrogen again in the form of H2. The
      optimized system therefore allowed the delta2H values of polyhalogenated
      compounds to be determined. A quality assurance program was developed based on
      several parameters. (i) Each compound was analyzed using a sequence of five
      injections, where the first measurement was discarded. (ii) Recovery of H (when
      calculated relative to acetanilide) had to be >90% for all replicates in a
      sequence. (iii) All delta-values within a sequence had to vary by less than
      10/1000. (iv) Results had to be reproducible on another day with a different
      sample scheme. Once this reproducibility had been established, variabilities in
      the delta2H values of organohalogen standards were investigated using the
      technique. The highest delta2H value of +75/1000 was found for o,p'-DDD, whereas
      the strongest depletion in deuterium was found for Melipax (-181/1000). The most
      important results for comparable compounds were as follows. DDT-related compounds
      gave delta2H values of between +59 and +75/1000 (technical DDT, o,p'- and p,p'
      DDD) or in the range of approximately -1/1000, indicative of the different
      sources/methods of producing this compound. Four HCH isomers from the same
      supplier showed relatively similar hydrogen isotope distributions, whereas two
      lindane (gamma-HCH) standards from other sources had 39/1000 less deuterium. This
      difference is likely due to different purification steps during the isolation of
      pure lindane from the technical HCH mixture. An even greater difference was
      observed between the delta2H values of Toxaphene (US product dating from 1978)
      and Melipax (product from the former East Germany, dating from 1979), which gave
      delta2H values of -101/1000 and -181/1000, respectively, meaning that both
      products were easily distinguished via delta2H-IRMS. Fractioning of hydrogen
      isotopes in the atmospheric water cycle was suggested as one reason for the
      different values. In this theory, the water (which had different delta2H values
      depending on where it was taken from) was incorporated during the biosynthesis of
      camphene, which is the natural product used to produce both products. These
      results indicate that hydrogen isotope-specific analysis can be a valuable tool
      for tracing the origins of a compound in certain cases.

PMID- 16283264
TI  - Ultrasensitive and rapid nanodevices for analytical immunoassays.

PMID- 16283265
TI  - Use of laser drilling in the manufacture of organic inverter circuits.
AB  - Inverter circuits have been made by connecting two high-quality pentacene field
      effect transistors. A uniform and pinhole-free 900 nm thick polyimide gate
      insulating layer was formed on a flexible polyimide film with gold gate
      electrodes and partially removed by using a CO2 laser drilling machine to make
      via holes and contact holes. Subsequent evaporation of the gold layer results in
      good electrical connection with a gold gate layer underneath the gate-insulating
      layer. By optimization of the settings of the CO2 laser drilling machine, contact
      resistance can be reduced to as low as 3 ohms for 180 microm square electrodes.
      No degradation of the transport properties of the organic transistors was
      observed after the laser-drilling process. This study demonstrates the
      feasibility of using the laser drilling process for implementation of organic
      transistors in integrated circuits on flexible polymer films.

PMID- 16283267
TI  - Nanomaterials in mass spectrometry ionization and prospects for biological
      application.
AB  - The rapid development of nanotechnology has revolutionized scientific
      developments in recent decades. Mass spectrometry (MS) measurements are no
      exception and have benefited greatly from integration of nanomaterials in every
      step of analysis. This brief review summarizes recent developments in the field
      with the focus on the use of nanomaterials as alternative media to facilitate
      analyte ionization in laser-desorption ionization-mass spectrometry (LDI-MS) and
      secondary ion mass spectrometry (SIMS). The biological applications of both
      techniques are also detailed. The use of nanomaterials in other aspects of MS
      analysis, for example in sample clean-up and indirect analyte quantification, is
      briefly discussed.

PMID- 16283268
TI  - In-depth profile analysis of thin films deposited on non-conducting glasses by
      radiofrequency glow-discharge-optical emission spectrometry.
AB  - The potential of radiofrequency glow-discharge-optical emission spectrometry (rf
      GD-OES) for quantification of thin films on non-conducting materials has been
      investigated. A commercial rf-GD chamber from Jobin Yvon operated at 13.56 MHz
      with Ar as discharge gas was used. The signal integration time was 0.1 s. The
      effect on emission yields of thin conducting layers on glasses of different
      thickness was studied in detail, using the rf-GD in the common operating mode
      "constant pressure-constant forward power". Calibration curves were obtained for
      two types of material-conducting reference materials and a set of non-conductors
      comprising homogeneous glass of known composition and three different thicknesses
      coated (or not) with thin layers of gold. Qualitative and quantitative in-depth
      profile analyses of different coated non-conducting samples were investigated. A
      variety of samples, including different thick glass substrates (from 1.8 to 5.8
      mm), different thin films deposited on homogeneous glasses (from 6 nm to 35 nm),
      and different kinds of coating (conductors such as Fe, Ni, Cr, Al, and Nb and non
      conductors such as Si3N4) were studied at 450 Pa pressure and 20 W forward power.
      The quantitative in-depth profiles proved satisfactory and results for depths and
      concentrations were similar to nominal values.

PMID- 16283266
TI  - Mapping and elemental fractionation of aerosols generated by laser-induced
      breakdown ablation.
AB  - Laser-induced breakdown spectroscopy (LIBS) has been used to map the distribution
      of particulate matter inside the plume created by laser ablation of a brass
      target. The spatial density distribution of the different components of the plume
      was determined in an attempt to reveal the mechanism of fractionation in the
      process of the laser ablation. In this experiment two Nd:YAG pulsed lasers were
      used. The first beam was focused on the target to generate a plume after
      breakdown of the surface. The second laser was focused on the plume and generated
      the second breakdown. The composition of the region probed by the second beam was
      determined by analyzing the spectral emission from the second breakdown. By
      scanning the probe time and position, the temporal and spatial evolution of the
      laser ablative plume could be discovered. Spatial and temporal fractionation was
      observed in brass plume.

PMID- 16283269
TI  - Isolation and determination of ginsenosides in American ginseng leaves and root
      extracts by LC-MS.
AB  - Ginseng saponins (ginsenosides) were extracted from the root and leaves of
      locally cultivated American ginseng (Panax quinquefolium L.). For the isolation
      of compounds from plant samples three different extraction methods were utilized:
      accelerated solvent extraction, the ultrasound-assisted solvent extraction and
      mechanical shaking assisted solvent extraction. The separation of compounds was
      achieved with a water-acetonitrile gradient system using a C18 reversed-phase
      column. Target compounds were identified in MS(2) and MS(3) experiments. The
      relative distribution of these ginsenosides in each root and leaf extract was
      established. The limit of detection of the method was less than 30 ng/ml.
      Recovery of ginseng saponins in spiked samples exceeded 80%, while the relative
      standard deviation ranged from 7.1 to 9.1%. The total concentrations of
      ginsenosides were 41 and 13 mg/g in root and leaves.

PMID- 16283270
TI  - Capillary-channeled polymer (C-CP) fibers as a stationary phase in microbore high
      performance liquid chromatography columns.
AB  - Microbore columns utilizing polypropylene capillary-channeled polymer (C-CP)
      fibers as the stationary phase in high-performance liquid chromatography (HPLC)
      have been investigated. The polypropylene C-CP fiber diameter is approximately 50
      microm, with eight channels along the periphery of the fiber ranging in diameter
      from approximately 12 to 35 microm. The polypropylene C-CP fibers were packed
      into fluorinated ethylene propylene (FEP) tubing, 1.3 mm inner diameter, with
      lengths of 500, 750, and 1,000 mm, to examine the effects of increased column
      length with regards to plate height, resolution and analysis time. The low
      backpressures characteristic of the C-CP fiber stationary phases allow the length
      of the column to be increased without significantly decreasing the specific
      permeability. The high specific permeability (approximately 5x10(-8) cm2) of the
      C-CP packed microbore columns yields a relatively low backpressure of 2.35 MPa at
      the highest flow rate of 17 microL/s (54 mm/s) for a 1,000 mm column. Radial
      compression of the soft-walled FEP tubing is accomplished by pulling the 1.7 mm
      o.d. column through a 1.4 mm diameter orifice. Reducing the inner diameter of the
      column from 1.3 to 1.0 mm lowered the interstitial fraction from 47% to 42%,
      decreased the A-term contributions to band broadening, resulted in a significant
      decrease in average plate height (approximately 30%), and increased resolution
      (approximately 36%) at identical linear velocities. Although the lower void
      volume of the radially compressed column increased the backpressure from 0.57 to
      2.11 MPa at a linear velocity of approximately 20 mm/s, the specific permeability
      only decreased from approximately 7x10(-8) to 4x10(-8) cm2.

PMID- 16283273
TI  - O-demethylation of tramadol in the first months of life.
AB  - OBJECTIVE: Assess in vivo O-demethylation activity in the first months of life.
      METHODS: Time-concentration profiles of tramadol (M) and O-demethyl tramadol (M1)
      in plasma and urine were simultaneously collected in the first 24 h of continuous
      intravenous tramadol administration in neonates and young infants. M and M1 were
      determined by high performance liquid chromatography. Correlations between
      perinatal characteristics [postnatal age (PNA), postmenstrual age (PMA)] and the
      contribution of metabolites (M, M1) to overall tramadol elimination and to the
      plasma and urine log M/M1 were calculated. RESULTS: Plasma samples were available
      in 20/29 and complete 24-h urine collections were available in 25/29 neonates (25
      53 weeks PMA). Mean plasma log M/M1 value (>4 h, n=86) was 0.8 (SD 0.4). A
      significant correlation between plasma log M/M1 and PMA (r=-0.73, P<0.0001) and
      PNA (r=-0.58, P<0.005) was observed. In a multiple regression model, only PMA
      remained an independent variable. Mean urine log M/M1 was 0.94 (SD 0.7).
      Significant correlations of the urine log M/M1 ratio with PMA (r=-0.73, P<0.0001)
      and PNA (r=-0.56, P=0.0035) were observed. In a multiple regression model with
      the urine log M/M1 ratio as dependent variable, only PMA remained an independent
      variable. The maturational half-life of the log M/M1 ratio in early neonatal life
      in the age range evaluated is about 12-16 weeks without plateau. CONCLUSIONS: O
      demethylation activity was already observed in early neonatal life. A significant
      correlation with PMA was documented, but PMA can only partially explain the
      observed variability in O-demethylation activity. Polymorphism therefore likely
      already contributes to the interindividual variability observed in neonates.

PMID- 16283274
TI  - Identification of CYP2D6 impaired functional alleles in Mexican Americans.
AB  - OBJECTIVES: To extend the genotyping analysis of the CYP2D6 gene and further
      explain variability of CYP2D6 activity in Mexican Americans by genetic factors.
      METHODS: CYP2D6 gene sequence variations associated with *6, *7, *8, *9, *11,
      *14, *29, *41, *45, and *46 alleles as well as the 2988G>A SNP were examined in
      264 Mexican Americans; 236 had previously been phenotyped with dextromethorphan.
      All subjects were previously genotyped for CYP2D6*2, *3, *4, *5, *10, *17, and
      the presence of a gene duplication. Associations between genotype and CYP2D6
      activity were determined. RESULTS: Mexican Americans revealed a high frequency of
      functional alleles (CYP2D6*1 and *2; 73.1%), followed by CYP2D6*4 (non
      functional, 10.0%) and the reduced-function allele *41 (9.5%). The frequencies of
      CYP2D6*5, *6, *9, *10, duplication, and 2988A were 1.7%, 0.4%, 1.1%, 2.8%, 0.8%,
      and 5.7%, respectively. CYP2D6*3, *17, and *29 were found only in one individual
      (CYP2D6*2/*3, *1/*17, and *4/*29), while CYP2D6*7, *8, *11, *14, *45, and *46
      were absent in this study population. Decreased CYP2D6 activity was more
      accurately predicted by the presence *41[-1584C] compared to *41[2988A]. One
      genotype/phenotype discordant subject was resolved by the presence of a CYP2D6*6
      allele (*4/*6), while two other cases remained discordant (*41/*41 and *1/*1).
      CONCLUSIONS: The CYP2D6*4, *5, and *6 null alleles along the reduced function
      alleles *9, *10, and *41 are the major cause for diminished dextromethorphan
      oxidative capacity in Mexican Americans. These findings may have implications for
      the safety and efficacy of CYP2D6 substrates taken by Mexican Americans.

PMID- 16283275
TI  - Effect of gemfibrozil on the pharmacokinetics of pioglitazone.
AB  - OBJECTIVE: Our objective was to study the effects of gemfibrozil on the
      pharmacokinetics of pioglitazone and the active compounds, which are all the
      substrates of CYP2C8 and CYP3A4. METHODS: In a randomized, two-phase crossover
      study, 10 healthy volunteers were pretreated for 2 days with either 600 mg oral
      gemfibrozil or placebo twice daily. On day 3, they received a single dose of 600
      mg gemfibrozil or placebo, and 1 h later they received a single oral dose of 30
      mg pioglitazone. Plasma concentrations of pioglitazone and both active
      metabolites M-III and M-IV were measured for up to 120 h. RESULTS: Gemfibrozil
      raised the mean total area under the concentration-time curve (AUC) of parent
      pioglitazone 3.4-fold (P<0.001). No statistically significant changes were seen
      in the total AUC of M-III or M-IV after gemfibrozil pretreatment. Gemfibrozil
      reduced the M-III/pioglitazone and M-IV/pioglitazone AUC(0-infinity) ratio by 71%
      (P<0.001) and 65%(P<0.001), strikingly prolonging their t((1/2)). CONCLUSION:
      Gemfibrozil greatly increased the plasma concentration of parent pioglitazone and
      also inhibited the further metabolism of M-III and M-IV. Careful blood glucose
      monitoring and dosage adjustments are suggested during coadministration of
      pioglitazone and gemfibrozil.

PMID- 16283276
TI  - CYP2D6 polymorphism, tramadol pharmacokinetics and pupillary response.

PMID- 16283277
TI  - Psychotropic combination in schizophrenia.
AB  - OBJECTIVE: To study adjunctive medications used with antipsychotic agents in
      schizophrenia via comparisons of antidepressant, anxiolytic and antiparkinsonian
      co-prescribing. METHOD: In the context of a national naturalistic prospective
      observational study, a database containing all the prescriptions from 100 French
      psychiatrists during the year 2002 was analysed. The inclusion criteria were a
      diagnosis of schizophrenia or schizoaffective disorder and age over 18. A log
      linear model and generalised linear mixed models were used. RESULTS: In all 5,257
      prescriptions for 922 patients were analysed. The proportion of patients who were
      prescribed an antiparkinsonian drug was 32.9%. Amisulpride, haloperidol,
      phenothiazines with a sedative action and depot typical antipsychotics proved
      more likely to be prescribed with antiparkinsonians. The frequency of
      antidepressant and anxiolytic prescriptions was 51.2% and 52.3%, respectively.
      Associations between atypical antipsychotics (except clozapine) and
      antidepressants were positive while associations between typical antipsychotics
      and antidepressants were not. There were no differences among antipsychotics for
      the prescription of anxiolytics. CONCLUSIONS: Atypical antipsychotics can be
      expected to be less likely associated with antiparkinsonians. This result is
      indeed found for olanzapine, clozapine and to a limited extent for risperidone.
      Furthermore, a trend towards a positive association between atypical
      antipsychotics and antidepressants appears. In view of the antidepressive action
      of certain atypical antipsychotics, this result is surprising. The increase in
      the prescriptions of anxiolytics concerns all types of antipsychotics. In view of
      the increase in associated medications in schizophrenia and the difficulty of
      estimating it in randomised trials, this study underlines the contribution of
      naturalistic studies on this score.

PMID- 16283282
TI  - Imaging characteristics of toxoplasmosis encephalitis after bone marrow
      transplantation: report of two cases and review of the literature.
AB  - Toxoplasmosis encephalitis is a severe, but often misdiagnosed complication in
      patients after bone marrow transplantation (BMT). We describe the unique computed
      tomography (CT) and magnetic resonance (MR) imaging features of cerebral
      toxoplasmosis in two bone marrow recipients and compare them to the cases in the
      literature. To our knowledge, this is the first report analyzing the appearance
      of cerebral toxoplasmosis on diffusion-weighted MR imaging (DWI).

PMID- 16283283
TI  - An incidental persistent falcine sinus with dominant straight sinus and
      hypoplastic distal superior sagittal sinus.
AB  - An incidental persistent falcine sinus was detected in an otherwise normal brain
      on MRI in a 12-year-old girl who underwent imaging after clinical suspicion of
      acute disseminated encephalomyelitis. The falcine sinus was associated with a
      hypoplastic posterior third of the superior sagittal sinus and a dominant
      straight sinus. Generally, atresia or hypoplasia of the straight sinus is
      associated with a persistent falcine sinus in postnatal life; otherwise, the
      falcine sinus disappears before birth. We discuss the embryological basis for
      such an association in this case.

PMID- 16283278
TI  - No evidence of gemcitabine accumulation during weekly administration.
AB  - Some anticancer agents tend to accumulate during repeated administration. We
      determined whether gemcitabine or its metabolites would accumulate during
      repeated administration. Gemcitabine was administered over two courses with each
      course consisting of a 30-min infusion at 1000 mg/m(2) weekly for 3 weeks
      followed by 1 week of rest. In 14 patients we evaluated eventual accumulation by
      comparing the concentrations in blood samples taken before, and at 30 and 60 min
      after the start of infusion on days 1, 8 and 15, in both cycles. At the end of
      the infusion gemcitabine concentrations at day 1 of both courses varied between
      18 and 77 microM and at day 15 between 13 and 90 microM. The mean ratios day
      8/day 1 and day 15/day 1 varied from 0.94 to 1.18. For the inactive metabolite
      2',2'-difluoro-2'-deoxyuridine (dFdU) these values varied between 54 and 152
      microM and 55 and 157, respectively, and the ratios from 0.96 to 1.08. The
      concentration of the active metabolite of gemcitabine, gemcitabine triphosphate
      (dFdCTP) in peripheral white blood cells, ranged between 37 and 283 pmol/10(6)
      cells at the end of infusion on day 1 and 35 and 115 pmol/10(6) cells on day 15.
      Potential accumulation was evaluated using a mixed effects model and no evidence
      was observed of accumulation for either gemcitabine or its metabolites.
      Gemcitabine can be administered safely without the risk that the drug will
      accumulate.

PMID- 16283284
TI  - Autosomal recessive polycystic kidney disease: appearance on fetal MRI.

PMID- 16283285
TI  - Comparative analysis of MR sequences to detect structural brain lesions in
      tuberous sclerosis.
AB  - BACKGROUND: Tuberous sclerosis (TS) is a neurocutaneous genetically inherited
      disease with variable penetrance characterized by dysplasias and hamartomas
      affecting multiple organs. MR is the imaging method of choice to demonstrate
      structural brain lesions in TS. OBJECTIVE: To compare MR sequences and determine
      which is most useful for the demonstration of each type of brain lesion in TS
      patients. MATERIALS AND METHODS: We reviewed MR scans of 18 TS patients for the
      presence of cortical tubers, white matter lesions (radial bands), subependymal
      nodules, and subependymal giant cell astrocytoma (SGCA) on the following
      sequences: (1) T1-weighted spin-echo (T1 SE) images before and after gadolinium
      (Gd) injection; (2) nonenhanced T1 SE sequence with an additional magnetization
      transfer contrast medium pulse on resonance (T1 SE/MTC); and (3) fluid-attenuated
      inversion recovery (FLAIR) sequence. RESULTS: Cortical tubers were found in
      significantly (P<0.05) larger numbers and more conspicuously in FLAIR and T1
      SE/MTC sequences. The T1 SE/MTC sequence was far superior to other methods in
      detecting white matter lesions (P<0.01). There was no significant difference
      between the T1 SE/MTC and T1 SE (before and after Gd injection) sequences in the
      detection of subependymal nodules; FLAIR sequence showed less sensitivity than
      the others in identifying the nodules. T1 SE sequences after Gd injection
      demonstrated better the limits of the SGCA. CONCLUSION: We demonstrated the
      importance of appropriate MRI sequences for diagnosis of the most frequent brain
      lesions in TS. Our study reinforces the fact that each sequence has a particular
      application according to the type of TS lesion. Gd injection might be useful in
      detecting SGCA; however, the parameters of size and location are also important
      for a presumptive diagnosis of these tumors.

PMID- 16283287
TI  - Lipomatous cortical dysplasia with callosal lipoma: a rare association.

PMID- 16283286
TI  - The Leech method for diagnosing constipation: intra- and interobserver
      variability and accuracy.
AB  - BACKGROUND: The data concerning the value of a plain abdominal radiograph in
      childhood constipation are inconsistent. Recently, positive results have been
      reported of a new radiographic scoring system, "the Leech method", for assessing
      faecal loading. OBJECTIVE: To assess intra- and interobserver variability and
      determine diagnostic accuracy of the Leech method in identifying children with
      functional constipation (FC). MATERIALS AND METHODS: A total of 89 children
      (median age 9.8 years) with functional gastrointestinal disorders were included
      in the study. Based on clinical parameters, 52 fulfilled the criteria for FC, six
      fulfilled the criteria for functional abdominal pain (FAP), and 31 for functional
      non-retentive faecal incontinence (FNRFI); the latter two groups provided the
      controls. To assess intra- and interobserver variability of the Leech method
      three scorers scored the same abdominal radiograph twice. A Leech score of 9 or
      more was considered as suggestive of constipation. ROC analysis was used to
      determine the diagnostic accuracy of the Leech method in separating patients with
      FC from control patients. RESULTS: Significant intraobserver variability was
      found between two scorers (P=0.005 and P<0.0001), whereas there was no systematic
      difference between the two scores of the other scorer (P=0.89). The scores
      between scorers differed systematically and displayed large variability. The area
      under the ROC curve was 0.68 (95% CI 0.58-0.80), indicating poor diagnostic
      accuracy. CONCLUSIONS: The Leech scoring method for assessing faecal loading on a
      plain abdominal radiograph is of limited value in the diagnosis of FC in
      children.

PMID- 16283288
TI  - Serial diffusion-weighted MRI correlates with clinical course and treatment
      response in children with intracranial pus collections.
AB  - BACKGROUND: Accurate assessment of treatment response in children with
      intracranial pus collections is vital to guide appropriate therapy and reduce
      morbidity and mortality. OBJECTIVE: To correlate serial MR-measurable changes in
      diffusion-weighted imaging (DWI) with clinical response to treatment. MATERIALS
      AND METHODS: We retrospectively reviewed clinical notes, conventional MR
      sequences and DWI in eight children with intracranial pus collections. Trace DWI
      signal intensity and apparent diffusion coefficient (ADC) values were compared at
      three time points: at initial diagnosis (eight children, 13 collections), at
      follow-up during continued clinical infection (three children, sp collections),
      and at follow-up when clinical infection had resolved (seven children, 12
      collections). RESULTS: At initial diagnosis all patients were septic and
      collections showed restricted diffusion (mean ADC 0.61+/-0.15 x 10(-3) mm(2)/s).
      Patients with persistent clinical sepsis at follow-up DWI had collections with
      persistent low ADC values (0.66+/-0.21 x 10(-3) mm(2)/s), significantly (P<0.001)
      below normal cortical gray matter values. Successful resolution of the infection
      was associated with a significant rise in ADC values (1.57+/-0.57 x 10(-3)
      mm(2)/s, P<0.01) compared both to patients with signs of continued sepsis and to
      normal gray matter values. CONCLUSION: Persistent restricted diffusion in pus
      collections correlates with continued sepsis. Treatment response is associated
      with clinical resolution of sepsis and ADC value elevation significantly above
      normal gray matter values.

PMID- 16283289
TI  - MRI assessment of bronchial compression in absent pulmonary valve syndrome and
      review of the syndrome.
AB  - Absent pulmonary valve syndrome (APVS) is a rare cardiac malformation with
      massive pulmonary insufficiency that presents with short-term and long-term
      respiratory problems secondary to severe bronchial compression from enlarged
      central and hilar pulmonary arteries. Association with chromosome 22.Q11
      deletions and DiGeorge syndrome is common. This historical review illustrates the
      airway disease with emphasis on assessment of the bronchial compression in
      patients with persistent respiratory difficulties post-valvular repair. Cases
      that had MRI for cardiac assessment are used to illustrate the pattern of airway
      disease.

PMID- 16283290
TI  - Impedance analysis of phosphatidylcholine membranes modified with valinomycin.
AB  - The effect of the ion carrier valinomycin on the electrochemical features of the
      phosphatidylcholine membrane was investigated by electrochemical impedance
      spectroscopy. Phosphatidylcholine and valinomycin were chosen for the study
      because they fulfil essential functions in lively organisms. The experimental
      impedance values obtained in the presence of different amounts of carrier,
      studied with several potassium ion concentrations, were used for the research
      ability of valinomycin to form a 1:1 potassium ion complex on the lipid
      bilayer/electrolyte solution interface. Based on derived mathematical equations,
      the heterogeneous equilibrium constant (K (h)), association rate constant of the
      complex (k (R)) and dissociation rate constant of the complex (k (D)) were
      calculated. The result of the investigation is the proposal of a new method for
      the determination of the parameters used to describe the chemical reaction at the
      interface between a carrier molecule from the membrane and a monovalent ion from
      the aqueous phase.

PMID- 16283291
TI  - Probing the importance of lateral hydrophobic association in self-assembling
      peptide hydrogelators.
AB  - A class of peptides has been designed whose ability to self-assemble into
      hydrogel is dependent on their conformationally folded state. Under unfolding
      conditions aqueous peptide solutions are freely flowing having the viscosity of
      water. When folding is triggered by external stimuli, peptides adopt a beta
      hairpin conformation that self-assembles into a highly crosslinked network of
      fibrils affording mechanically rigid hydrogels. MAX 1, a 20 residue, amphiphilic
      hairpin self-assembles via a mechanism which entails both lateral and facial self
      assembly events to form a network of fibrils whose local structure consists of a
      bilayer of hairpins hydrogen bonded in the direction of fibril growth. Lateral
      self-assembly along the long axis of the fibril is mainly facilitated by
      intermolecular hydrogen bonding between the strands of distinct hairpins and the
      formation of hydrophobic contacts between residue side chains of laterally
      associating hairpins. Facial assembly is driven by the hydrophobic collapse of
      the valine-rich faces of the amphiphilic hairpins affording a bilayer laminate.
      The importance of forming lateral hydrophobic contacts during hairpin self
      assembly and the relative contribution these interactions have towards nano-scale
      morphology and material rigidity is probed via the study of: MAX1, a hairpin
      designed to exploit lateral hydrophobic interactions; MAX 4, a peptide with
      reduced ability to form these interactions; and MAX5, a control peptide. CD
      spectroscopy and rheological experiments suggest that the formation of lateral
      hydrophobic interactions aids the kinetics of assembly and contributes to the
      mechanical rigidity of the hydrogel. Transmission electron microscopy (TEM) shows
      that these interactions play an essential role in the self-assembly process
      leading to distinct nano-scale morphologies.

PMID- 16283292
TI  - Multilamellarity, structure and hydration of extruded POPC vesicles by SANS.
AB  - The small-angle neutron scattering (SANS) data of 12 1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphocholine (POPC) dispersions at low lipid concentration (1 mg per
      100-mg heavy water) prepared by 5, 9 and 29 extrusions through filters of pores
      with 50, 100, 200 and 400 nm diameter are presented. They were analyzed within a
      theory that permits the determination of both structural and hydration parameters
      of the bilayers as well as the portions of multilamellar vesicles in dispersions
      with negligible long-range order between the vesicles. The scattering length
      density profile across the bilayers is approximated by assuming a central
      hydrocarbon core surrounded by a water-accessible coat. It is modeled by two
      different forms of functions. In the boat model, the scattering length density of
      the coat changes linearly from core to water, whereas in the strip model it is
      constant across the water-accessible coat. It was found that the boat model
      reflects the reality better than the strip model. The decrease of the
      multilamellar vesicle portions, either with increasing the number of extrusions
      at same filter size and with decreasing the filter size, was characterized
      quantitatively.

PMID- 16283293
TI  - Biochemical retrosynthesis of 2'-deoxyribonucleosides from glucose, acetaldehyde,
      and a nucleobase.
AB  - 2'-Deoxyribonucleosides are important as building blocks for the synthesis of
      antisense drugs, antiviral nucleosides, and 2'-deoxyribonucleotides for
      polymerase chain reaction. The microbial production of 2'-deoxyribonucleosides
      from simple materials, glucose, acetaldehyde, and a nucleobase, through the
      reverse reactions of 2'-deoxyribonucleoside degradation and the glycolytic
      pathway, was investigated. The glycolytic pathway of baker's yeast yielded
      fructose 1,6-diphosphate from glucose using the energy of adenosine 5'
      triphosphate generated from adenosine 5'-monophosphate through alcoholic
      fermentation with the yeast. Fructose 1,6-diphosphate was further transformed to
      2-deoxyribose 5-phosphate in the presence of acetaldehyde by deoxyriboaldolase
      expressing Escherichia coli cells via D-glyceraldehyde 3-phosphate. E. coli
      transformants expressing phosphopentomutase and nucleoside phosphorylase produced
      2'-deoxyribonucleosides from 2-deoxyribose 5-phosphate and a nucleobase via 2
      deoxyribose 1-phosphate through the reverse reactions of 2'-deoxyribonucleoside
      degradation. Coupling of the glycolytic pathway and deoxyriboaldolase-catalyzing
      reaction efficiently supplied 2-deoxyribose 5-phosphate, which is a key
      intermediate for 2'-deoxyribonucleoside synthesis. 2'-Deoxyinosine (9.9 mM) was
      produced from glucose, acetaldehyde, and adenine through three-step reactions via
      fructose 1,6-diphosphate and then 2-deoxyribose 5-phosphate, the molar yield as
      to glucose being 17.8%.

PMID- 16283294
TI  - Isolation and characterization of a phenol-degrading bacterium from an industrial
      activated sludge.
AB  - This paper reports the successful isolation and characterization of a new phenol
      degrading bacterium, strain EDP3, from activated sludge. Strain EDP3 is a
      nonmotile, strictly aerobic, Gram-negative, and short-rod or coccobacillary
      bacterium, which occurs singly, in pairs, or in clusters. 16S rRNA gene sequence
      analysis revealed that strain EDP3 belonged to the gamma group of Proteobacteria,
      with a 97.0% identity to 16S rRNA gene sequences of Acinetobacter calcoaceticus.
      Strain EDP3 could aerobically grow on a number of aromatic compounds, such as
      phenol, sodium benzoate, p-hydroxybenzoate, phenylacetate, benzene, ethylbenzene,
      benzylalcohol, and so on. In particular, it could mineralize up to 1,000 mg l(-1)
      phenol at room temperature (25 degrees C). The growth kinetics of strain EDP3 on
      phenol as a sole carbon and energy source at 25 degrees C can be described using
      the Haldane equation. It has a maximal specific growth rate (mu(max)) of 0.28 h(
      1), a half-saturation constant (K(S)) of 1,167.1 mg l(-1), and a substrate
      inhibition constant (Ki) of 58.5 mg l(-1). Values of yield coefficient (Y(X/S))
      are between 0.4 and 0.6 mg dry cell (mg phenol)(-1). Strain EDP3 has high
      tolerance to the toxicity of phenol (up to 1,000 mg l(-1)). It therefore could be
      an excellent candidate for the biotreatment of high-strength phenol-containing
      industrial wastewaters and for the in situ bioremediation of phenol-contaminated
      soils.

PMID- 16283295
TI  - Aptamers--basic research, drug development, and clinical applications.
AB  - Since its discovery in the early 1990s, aptamer technology has progressed
      tremendously. Automated selection procedures now allow rapid identification of
      DNA and RNA sequences that can target a broad range of extra- and intracellular
      proteins with nanomolar affinities and high specificities. The unique binding
      properties of nucleic acids, which are amenable to various modifications, make
      aptamers perfectly suitable for different areas of biotechnology. Moreover, the
      approval of an aptamer for vascular endothelial growth factor by the US Food and
      Drug Administration highlights the potential of aptamers for therapeutic
      applications. This review summarizes recent developments and demonstrates that
      aptamers are valuable tools for diagnostics, purification processes, target
      validation, drug discovery, and even therapeutic approaches.

PMID- 16283296
TI  - Comparative analysis of transcriptional responses to saline stress in the
      laboratory and brewing strains of Saccharomyces cerevisiae with DNA microarray.
AB  - To construct yeast strains showing tolerance to high salt concentration stress,
      we analyzed the transcriptional response to high NaCl concentration stress in the
      yeast Saccharomyces cerevisiae using DNA microarray and compared between two
      yeast strains, a laboratory strain and a brewing one, which is known as a stress
      tolerant strain. Gene expression dynamically changed following the addition of
      NaCl in both yeast strains, but the degree of change in the gene expression level
      in the laboratory strain was larger than that in the brewing strain. The response
      of gene expression to the low NaCl concentration stress was faster than that to
      the high NaCl concentration stress in both strains. Expressions of the genes
      encoding enzymes involved in carbohydrate metabolism and energy production in
      both strains or amino acid metabolism in the brewing strain were increased under
      high NaCl concentration conditions. Moreover, the genes encoding sodium ion
      efflux pump and copper metallothionein proteins were more highly expressed in the
      brewing strain than in the laboratory strain. According to the results of
      transcriptome analysis, candidate genes for the creation of stress-tolerant
      strain were selected, and the effect of overexpression of candidate genes on the
      tolerance to high NaCl concentration stress was evaluated. Overexpression of the
      GPD1 gene encoding glycerol-3-phosphate dehydrogenase, ENA1 encoding sodium ion
      efflux protein, and CUP1 encoding copper metallothionein conferred high salt
      stress tolerance to yeast cells, and our selection of candidate genes for the
      creation of stress-tolerant yeast strains based on the transcriptome data was
      validated.

PMID- 16283297
TI  - Automated feeding strategies for high-cell-density fed-batch cultivation of
      Pseudomonas putida KT2440.
AB  - Four automatic substrate feeding strategies were developed and investigated in
      this study to obtain rapid, repeatable, and reliable high cell densities of
      Pseudomonas putida KT2440 from glucose. Growth yield data of the key nutrients,
      Y(X/Glucose), Y(X/NH4), Y(X/PO4), Y(X/Mg), and Y(CO2/Glucose), were determined to
      be 0.41, 5.44, 13.70, 236, and 0.65 g g(-1), respectively. Although standard
      exponential feeding strategy worked well when the predetermined mu was set at
      0.25 h(-1), an exponential glucose feeding strategy with online mu(max)
      estimation resulted in a higher average biomass productivity (3.4 vs 2.8 g l(-1)
      h(-1)). A CO2 production rate based pulse glucose feeding strategy also resulted
      in good overall productivity (3.0 g l(-1) h(-1)) and can be used as an
      alternative to pH-stat or DO-stat feeding. A cumulative CO2 production based
      continuous feed with real-time cumulative glucose consumption estimation resulted
      in much higher biomass productivity (4.3 g l(-1) h(-1)) and appears to be an
      excellent and reliable approach to fully automating high-cell-density fed-batch
      cultivation of P. putida.

PMID- 16283298
TI  - Cloning of novel laccase isozyme genes from Trametes sp. AH28-2 and analyses of
      their differential expression.
AB  - Three novel laccase isozyme genes, lacA, lacB, and lacC, have been identified
      from basidiomycete Trametes sp. AH28-2. These genes display a high similarity
      with other basidiomycete laccases at the amino acid level. An inferred TATA box
      and several putative CAAT, MRE, XRE, and CreA consensus sequences were identified
      in the lacA, lacB, and lacC promoter regions. Different from the TATA boxes of
      lacA and lacB at about -100, the TATA box of lacC is located at -172. For all the
      isozymes, copper ion is essential for laccase synthesis in Trametes sp. AH28-2.
      More interestingly, different aromatic compounds can selectively induce the
      production of distinct laccase isozymes, with o-toluidine inducing the expression
      of laccase A (LacA) while 3,5-dihydroxytoluene mainly stimulating the production
      of laccase B (LacB). Quantitative reverse transcriptase-polymerase chain reaction
      showed that the accumulation of laccase messenger RNA transcripts is accompanied
      by the increase of corresponding enzyme activity in cultures. The glucose
      repression effect on laccase expression in Trametes sp. AH28-2 was also observed.
      Furthermore, lower Cu2+ concentration (lower than 0.5 mM) can induce LacA and a
      novel laccase (LacC), and the latter will disappear when Cu2+ concentration is
      increased up to 1-2 mM. Upon induction by 3,5-dihydroxytoluene, the ratio of LacA
      to LacB decreased in the later phase of induction.

PMID- 16283299
TI  - Expression of the urease gene of Agaricus bisporus: a tool for studying fruit
      body formation and post-harvest development.
AB  - Fruit body initials of Agaricus bisporus contain high levels of urea, which
      decrease in the following developmental stages until stage 4 (harvest) when urea
      levels increase again. At storage, the high urea content may affect the quality
      of the mushroom, i.e. by the formation of ammonia from urea through the action of
      urease (EC 3.5.1.5). Despite the abundance of urea in the edible mushroom A.
      bisporus, little is known about its physiological role. The urease gene of A.
      bisporus and its promoter region were identified and cloned. The coding part of
      the genomic DNA was interrupted by nine introns as confirmed by cDNA analysis.
      The first full homobasidiomycete urease protein sequence obtained comprised 838
      amino acids (molecular mass 90,694 Da, pI 5.8). An alignment with fungal, plant
      and bacterial ureases revealed a high conservation. The expression of the urease
      gene, measured by Northern analyses, was studied both during normal development
      of fruit bodies and during post-harvest senescence. Expression in normal
      development was significantly up-regulated in developmental stages 5 and 6.
      During post-harvest senescence, the expression of urease was mainly observed in
      the stipe tissue; expression decreased on the first day and remained at a basal
      level through the remaining sampling period.

PMID- 16283300
TI  - A homologue of cathepsin L identified in conditioned medium from Sf9 insect
      cells.
AB  - Gelatin zymography revealed the presence of proteolytic activity in conditioned
      medium (CM) from a serum-free, non-infected Spodoptera frugiperda, Sf9 insect
      cell culture. Two peptidase bands at about 49 and 39 kDa were detected and found
      to be proform and active form of the same enzyme. The 49-kDa form was visible on
      zymogram gels in samples of CM taken on days 4 and 5 of an Sf9 culture, while the
      39-kDa form was seen on days 6 and 7. On basis of the inhibitor profile and
      substrate range, the enzyme was identified as an Sf9 homologue of cathepsin L, a
      papain-like cysteine peptidase. After lowering the pH of Sf9 CM to 3.5, an
      additional peptidase band at 22 kDa appeared. This peptidase showed the same
      inhibitor profile, substrate range and optimum pH (5.0) as the 39-kDa form,
      indicating that Sf9 cathepsin L has two active forms, at 39 and 22 kDa. Addition
      of the cysteine peptidase inhibitor E-64c to an Sf9 culture inhibited all
      proteolytic activities of Sf9 cathepsin L but did not influence the proliferation
      of Sf9 cells.

PMID- 16283301
TI  - Degradation of toxaphene by Bjerkandera sp. strain BOL13 using waste biomass as a
      cosubstrate.
AB  - The white-rot fungus Bjerkandera sp. strain BOL13 was capable of degrading
      toxaphene when supplied with wood chips, wheat husk or cane molasses as
      cosubstrates in batch culture experiments. Approximately 85% of toxaphene was
      removed when wheat husk was the main substrate. The production of lignin
      peroxidase was only stimulated when wheat husk was present in the liquid medium.
      Although xylanase was always detected, wheat husk supported the highest xylanase
      production. A negligible amount of beta-glucosidase and cellulase were found in
      the batch culture medium. To the best of our knowledge, this is the first
      reported case of toxaphene degradation by white-rot fungi.

PMID- 16283302
TI  - In vivo hypolipidemic effects and safety of low dosage Monascus powder in a
      hamster model of hyperlipidemia.
AB  - Monascus or more commonly known as red mold rice is fermented rice on which
      Monascus purpureus has been grown. It has been a traditional Chinese food
      additive for thousands of years in China. Secondary metabolite product of
      Monascus, monacolin K, has been proven that it could be used as an
      antihypercholesterolemic agent. In this study, M. purpureus NTU568 mutated and
      selected from a monacolin K productivity strain-M. purpureus HM105 produced high
      quantities of monacolin K at a level of 9,500 mg kg(-1). This research focused on
      the effect of adding red mold rice powder of M. purpureus NTU568 to a hamster
      diet on total cholesterol (TC), triglyceride (TG), high-density lipoprotein
      cholesterol, and low-density lipoprotein cholesterol (LDL-C). In the results, the
      oral administration of Monascus powder in hyperlipidemia hamster was indeed
      proven to decrease TC, TG, and LDL-C levels. Plasma TC levels in hamster fed with
      Monascus powder at one-fold dosage [10.78 mg (day 100 g bw)(-1)] for 4 and 8
      weeks were significantly lower (31.2 and 22.0%, respectively) than that in
      hyperlipidemia hamster. Plasma TG (30.1 and 17.9%) and LDL-C levels (36.0 and
      20.7%) were also significantly lowered by feeding Monascus powder at one-fold
      dosage for 4 and 8 weeks compared to hyperlipidemia hamster. In addition,
      examinations of liver TC and TG levels of hyperlipidemia hamster were also
      performed and showed similar effects on lipid-lowering action by oral
      administration of Monascus powder. Since citrinin is a mycotoxin that possesses
      nephrotoxic and hepatoxic effects, it has a negative impact on the safety of red
      mold rice for people. This study examined the liver somatic index [plasma
      glutamyl oxaloacetic transaminase (GOT) and glutamyl pyruvic transaminase (GPT)
      levels] and liver biopsy to investigate whether Monascus powder induced damage in
      liver. It was found that the plasma GOT and GPT levels were not significantly
      increased by feeding Monascus powder. There was no difference in the results of
      the liver biopsy between the Monascus powder-treated groups and the control
      group.

PMID- 16283303
TI  - Induction of specific T cell immunity in patients with prostate cancer by
      vaccination with PSA146-154 peptide.
AB  - T cell immunotherapy of prostate cancer (CaP) offers the potential for less
      toxic, more effective outcomes. A clinical trial was conducted in 28 patients
      with locally advanced or metastatic CaP to determine whether an HLA-A2 binding
      epitope of prostate-specific antigen, PSA146-154 (PSA-peptide), can induce
      specific T cell immunity. Patients were vaccinated either by intradermal
      injection of PSA-peptide and GM-CSF or by intravenous administration of
      autologous dendritic cells pulsed with PSA-peptide at weeks 1, 4 and 10. Delayed
      type hypersensitivity (DTH) skin testing was performed at weeks 4, 14, 26 and 52.
      Fifty percent of the patients developed positive DTH responses to PSA-peptide.
      The size of the DTH induration progressively increased over time in the majority
      of responding patients. Skin biopsies from seven DTH-positive patients were
      available and T cells that developed in situ were also characterized. The
      phenotype of recovered T cells demonstrated variable proportions of CD4+CD8-, CD4
      CD8+ and CD4+CD8+ T cell populations. Cytokine analysis of PSA-peptide stimulated
      T cells per bead array assay exhibited specific IFN-gamma and TNF-alpha response
      in six of seven patients. Specific IL-4 response was observed in five patients,
      while IL-10 response was detected in one patient. Purified CD4-CD8+ T cells
      isolated from four patients demonstrated specific cytolytic activity per chromium
      release assay. In conclusion, immunization with PSA-peptide induced specific T
      cell immunity in one-half of the patients with locally advanced and hormone
      sensitive, metastatic CaP. DTH-derived T cells exhibited PSA-peptide-specific
      cytolytic activity and predominantly expressed a type-1 cytokine profile.

PMID- 16283304
TI  - Functional endogenous cytotoxic T lymphocytes are generated to multiple antigens
      co-expressed by progressing tumors; after intra-tumoral IL-2 therapy these
      effector cells eradicate established tumors.
AB  - Tumors contain many antigens that may be recognized by the immune system. It is
      not known whether these antigens, and the epitopes within these antigens, can all
      be recognized by the anti-tumor immune response or if such responses are
      restricted to a few dominant epitopes. Effector function of endogenous cytotoxic
      T lymphocytes (CTL) generated during tumor progression has previously been
      assessed by indirect, ex vivo assays, which often focused on a single antigen.
      Therefore, we evaluated the endogenous in vivo CTL response to multiple neo tumor
      antigens using murine Lewis lung carcinoma tumor cells transfected with ovalbumin
      or a polyepitope construct. Both express multiple MHC class I-restricted
      epitopes. Ovalbumin contains a known hierarchy of epitopes for given MHC
      molecules, whilst the polyepitope expresses a number of dominant epitopes. We
      show that as tumors progress, potent effector CTL are generated in vivo that are
      restricted to dominant epitopes; we did not see the responses to subdominant or
      cryptic epitopes. Our data show that the CTL recognizing tumor antigens vary in
      their lytic capacity, as the CTL responding to two of the four epitopes were
      particularly potent killers. The presence of these effector CTLs did not prevent
      tumor growth. However, intra-tumoral IL-2 treatment altered the potency, but not
      the hierarchy, of these CTL such that they mediated tumor regression. These
      results have implications for immunotherapy protocols.

PMID- 16283305
TI  - Tumour-derived microvesicles carry several surface determinants and mRNA of
      tumour cells and transfer some of these determinants to monocytes.
AB  - This study was designed to determine the characteristics of tumour cell-derived
      microvesicles (TMV) and their interactions with human monocytes. TMV were shed
      spontaneously by three different human cancer cell lines but their release was
      significantly increased upon activation of the cells with phorbol 12-myristate 13
      acetate (PMA). TMV showed the presence of several surface determinants of tumour
      cells, e.g. HLA class I, CD29, CD44v7/8, CD51, chemokine receptors (CCR6,
      CX3CR1), extracellular matrix metalloproteinase inducer (EMMPRIN), epithelial
      cell adhesion molecule (EpCAM), but their level of expression differed from that
      on cells they originated from. TMV also carried mRNA for growth factors: vascular
      endothelial growth factor (VEGF), hepatocyte growth factor (HGF), interleukin-8
      (IL-8) and surface determinants (CD44H). TMV were localized at the monocytes
      surface following their short exposure to TMV, while at later times
      intracellularly. TMV transferred CCR6 and CD44v7/8 to monocytes, exerted
      antiapoptotic effect on monocytes and activated AKT kinase (Protein Kinase B).
      Thus, TMV interact with monocytes, alter their immunophenotype and biological
      activity. This implicates the novel mechanism by which tumour infiltrating
      macrophages may be affected by tumour cells not only by a direct cell to cell
      contact, soluble factors but also by TMV.

PMID- 16283306
TI  - Flow cytometric analysis of Th1 and Th2 cytokines in PBMCs as a parameter of
      immunological dysfunction in patients of superficial transitional cell carcinoma
      of bladder.
AB  - Transitional cell carcinoma (TCC) is the commonest cancer of the bladder.
      Although majority of TCC can be diagnosed at an early stage and removed easily by
      transurethral resection of tumor (TURT), the management of this carcinoma is
      complicated due to frequent recurrences usually within 6 months to one-year
      period. An imbalance between the Th1 and Th2 immune responses has been attributed
      to immune dysregulation in various malignancies. The present study aims to
      evaluate the Th1 and Th2 balance in Peripheral Blood Mononuclear Cells of 41 TCC
      patients (20 recurrent and 21 non-recurrent) using flow cytometry. It also
      further assesses immunological and cellular factors influencing the anti
      neoplastic activity of the TCC patients and in 21 normal healthy subjects in
      terms of their cytokine expression and various cell surface markers. The findings
      of the study revealed that the cell surface markers CD3+, CD4+ and CD8+ along
      with NK cells were found to be significantly lower in patients than healthy
      controls (p < 0.01). The mean percent expression of CD4+ was significantly lower
      in patients showing recurrence (23.9 +/- 9.84) as compared to patients with non
      recurrence (31.1 +/- 12.27). The percentage of CD4+T-cells (mean +/- SD)
      producing IFN-gamma, IL-2 and TNF-alpha were statistically significantly reduced
      in patients (19.1 +/- 4.94, 52.3 +/- 20.86 and 12.8 +/- 4.49) as compared to
      healthy controls (23.3 +/- 3.67, 67.5 +/- 12.0 and 17.6 +/- 5.96 respectively),
      (p < 0.01, 0.018, 0.001). On the contrary, the mean levels of IL-4, IL-6 and IL
      10 in patients (63.8+/-17.01, 60.4+/-14.79 and 65.7 +/- 14.84 respectively) were
      significantly higher as compared to healthy controls (24.4 +/- 8.77, 26.5 +/-
      5.28 and 20.6 +/- 3.81 respectively), (p < 0.001). No statistically significant
      difference was observed in the cytokine expression between patients showing
      recurrence and non-recurrence. Patients with bladder cancer seem to develop a Th2
      dominant status with a deficient type1 immune response. The lymphocyte evaluation
      along with cytokine measurement can provide a sensitive and valuable tool for
      evaluating the function of cell-mediated immunity in these patients and can also
      find application in therapeutic monitoring of bladder cancer patients as new
      targets for immunotherapy.

PMID- 16283307
TI  - Early polyethylene wear and osteolysis with ABG acetabular cups (7- to 12-year
      follow-up).
AB  - We reviewed 81 consecutive ABG I primary total hip replacements implanted in 72
      patients between January 1993 and December 1998. The mean follow-up was 8.2
      (range 7-12) years. There was significant polyethylene wear and osteolysis
      associated with the acetabular cup . The cumulative survival of the cup with
      revision being the end point at 8.2 years was 95.1% (95% CI: 92-97.6%). However,
      the cumulative survival of the cup with revision and aseptic loosening together
      was 72% (95% CI: 61-78%) and survival of the acetabular liner for wear was 62%
      (95% CI: 48-74%). Stem survival with revision being the end point was 100%. In
      spite of significant radiological failures of the cups, most patients remained
      asymptomatic. Though results of the ABG stems in this series were good, we
      advocate a regular follow-up of all these hips in view of the poor outcome of the
      cups.

PMID- 16283308
TI  - Agonists-induced platelet activation varies considerably in healthy male
      individuals: studies by flow cytometry.
AB  - Flow cytometric evaluation of platelet function extends our understanding of
      platelets' role in various clinical conditions associated with either bleeding
      disorders, thrombosis, or monitoring of antiplatelet therapy. The use of
      suboptimal concentrations of various agonists may allow assessing the
      "activatability" of platelets. We determined platelet responsiveness to thrombin
      receptor-activating peptide-6, arachidonic acid, adenosine 5c-diphosphate (ADP),
      epinephrine, collagen, and ristocetin at suboptimal concentrations by
      determination of P-selectin expression and binding of PAC-1 in 26 healthy male
      individuals. The response varied considerably from one individual to the next.
      However, within individuals, responses to all agonists except collagen correlated
      strongly (p<0.05), suggesting a global variability of platelet responses.
      Moreover, P-selectin expression and PAC-1 binding were strongly correlated
      (p<0.05). Interestingly, with epinephrine, PAC-1 positive events outnumbered P
      selectin positive events, while this was not seen with the other agonists. Thus,
      epinephrine may specifically affect the conformational switch mechanism and
      receptor clustering. Our data indicate that the in vitro response to suboptimal
      concentrations of agonists varies, but individuals with selective platelet
      defects may still be identified based on data obtained with the various agonists.

PMID- 16283309
TI  - Prothrombin G20210A gene variant is not associated with idiopathic portal vein
      thrombosis in an area endemic for portal vein thrombosis.
AB  - Prothrombin G20210A gene variant has been found in 0-23% of patients with portal
      vein thrombosis (PVT). This wide variation makes it difficult to assess the
      importance of prothrombin G20210A gene variant as a predisposing factor for PVT.
      In this study from South India, none of the patients with idiopathic PVT (0/38)
      or any of the controls (0/46) had prothrombin G20210A gene variant. Prothrombin
      G20210A gene variant does not contribute to the development of PVT in India.

PMID- 16283310
TI  - Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell
      lung cancer cells.
AB  - Cisplatin produces good responses in solid tumours including small cell lung
      cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin
      is reported to show activity against some cisplatin-resistant cancers but there
      is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin
      resistant SCLC cell lines. Studies of drug resistance mainly focus on the
      cellular resistance mechanisms rather than how the cells develop resistance. This
      study examines the development of cisplatin and oxaliplatin resistance in H69
      human SCLC cells in response to repeated treatment with clinically relevant doses
      of cisplatin or oxaliplatin for either 4 days or 2 h. Treatments with 200 ng/ml
      cisplatin or 400 ng/ml oxaliplatin for 4 days produced sublines (H69CIS200 and
      H69OX400, respectively) that showed low level (approximately two-fold) resistance
      after eight treatments. Treatments with 1,000 ng/ml cisplatin or 2,000 ng/ml
      oxaliplatin for 2 h also produced sublines, however, these were not stably
      resistant suggesting shorter treatment pulses of drug may be more effective.
      Cells survived the first five treatments without any increase in resistance, by
      arresting their growth for a period and then regrowing. The period of growth
      arrest was reduced after the sixth treatment and the H69CIS200 and H69OX400
      sublines showed a reduced growth arrest in response to cisplatin and oxaliplatin
      treatment suggesting that 'regrowth resistance' initially protected against drug
      treatment and this was further upregulated and became part of the resistance
      phenotype of these sublines. Oxaliplatin dose escalation produced more surviving
      sublines than cisplatin dose escalation but neither set of sublines were
      associated with increased resistance as determined by 5-day cytotoxicity assays,
      also suggesting the involvement of regrowth resistance. The resistant sublines
      showed no change in platinum accumulation or glutathione levels even though the
      H69OX400 subline was more sensitive to buthionine sulphoximine treatment. The
      H69CIS200 cells were cross-resistant to oxaliplatin demonstrating that
      oxaliplatin does not have activity against low level cisplatin resistance.
      Relative to the H69 cells, the H69CIS200 and H69OX400 sublines were more
      sensitive to paclitaxel and taxotere suggesting that the taxanes may be useful in
      the treatment of platinum-resistant SCLC. These novel cellular models of
      cisplatin and oxaliplatin resistant SCLC will be useful in developing strategies
      to treat platinum-resistant SCLC.

PMID- 16283311
TI  - Elemene displays anti-cancer ability on laryngeal cancer cells in vitro and in
      vivo.
AB  - PURPOSE: The goal of this study is to investigate the inhibitory effects and
      mechanism of elemene on the growth of laryngeal cancer cells in vitro and in
      vivo. METHODS: Laryngeal cancer cells (HEp-2 cells) were grown in elemene,
      cisplatin, or a combination of the drugs. The cytotoxic, or apoptotic, effects of
      elemene on the cells were evaluated by a 3-[4,5-dimethylthiazol-2yl]-2,5
      diphenyltetrazolium bromide assay, flow cytometry, and a caspase-3 activity
      assay. A Western blot was used to semi-quantify the protein expression of
      eukaryotic initiation factors (eIF4E and eIF4G), basic fibroblast growth factor
      (bFGF), and vascular endothelial growth factor (VEGF); RT-PCR analysis semi
      quantified the mRNA transcript expression of bFGF and VEGF. The HEp-2 cells were
      transplanted subcutaneously to BALB/c nude mice to produce solid tumors. Elemene
      and cisplatin were administered to the mice either as individual drugs or in
      combination. The tumors were excised and immunostained to determine the effect
      each drug had on tumor size, eIF levels, angiogenic factors, and microvessel
      density (MVD). RESULTS: Elemene inhibited the growth of HEp-2 cells in vitro in a
      dose- and time-dependent manner with an IC(50) of 346.5 microM (24 h incubation).
      Increased apoptosis was observed in elemene-administered cells. Elemene is
      suspected to enhance caspase-3 activity, and thus inhibit protein expression of
      eIFs (4E, 4G), bFGF, and VEGF. In vivo, the growth of HEp-2 cell-transplanted
      tumors in nude mice was inhibited by intraperitoneal injection of elemene.
      Compared with control groups, elemene significantly inhibited the protein
      expression of eIFs (4E and 4G), bFGF, and VEGF and decreased the MVD.
      CONCLUSIONS: Elemene inhibits the growth of HEp-2 cells in vitro and in vivo.
      These data provide useful information for further clinical study on the treatment
      of LSCC by elemene.

PMID- 16283312
TI  - Combination vinorelbine and capecitabine for metastatic breast cancer using a non
      body surface area dosing scheme.
AB  - PURPOSE: This study sought to determine the maximum tolerated dose of flat-dosed
      vinorelbine in combination with capecitabine in patients with metastatic breast
      cancer. At the time of study initiation, it was anticipated that vinorelbine
      would be developed as an oral capsule. A flat dosing scheme of both drugs was
      used to facilitate development of the oral regimen, and because neither drug's
      clearance is associated with body surface area (BSA), pharmacokinetic and
      pharmacogenetic endpoints were explored. EXPERIMENTAL DESIGN: Capecitabine was
      administered orally at 3,000 mg/day on days 1-14. The starting dose of
      vinorelbine was 20 mg intravenously on days 1 and 8 of a 21-day cycle. The
      vinorelbine dose was escalated until dose limiting toxicity (DLT). Vinorelbine
      pharmacokinetics were measured after the first dose. Patients underwent genotype
      analysis for polymorphisms in the CYP3A5 gene, and the erythromycin breath test
      (ERMBT), a phenotypic test of CYP3A enzyme activity. RESULTS: Twenty five
      eligible patients were enrolled. Hematologic DLT was seen at the 50 and 45 mg
      vinorelbine doses; thus the recommended dose is 40 mg on days 1 and 8. Response
      rate was 30%, and disease stabilization rate was 64% (all dose levels included).
      Vinorelbine clearance was not associated with ERMBT, BSA, or age. CYP3A5 genotype
      in this small sample did not have an obvious relationship to clearance or
      toxicity. CONCLUSIONS: A non-BSA based dosing scheme of capecitabine and
      vinorelbine is safe and efficacious. BSA did not affect vinorelbine clearance. We
      recommend future studies with capecitabine and/or vinorelbine to compare the
      safety and efficacy of flat dosed versus BSA-dosed treatment.

PMID- 16283313
TI  - Diversity of the exoproteome of Fusarium graminearum grown on plant cell wall.
AB  - The exoproteome of the fungus Fusarium graminearum grown on glucose and on hop
      (Humulus lupulus, L.) cell wall has been investigated. The culture medium was
      found to contain a higher quantity of proteins and the proteins are more diverse
      when the fungus is grown on cell wall. Using both 1D and 2D electrophoresis
      followed by mass spectrometry analysis and protein identification based on
      similarity searches, 84 unique proteins were identified in the cell wall-grown
      fungal exoproteome. Many are putatively implicated in carbohydrate metabolism,
      mainly in cell wall polysaccharide degradation. The predicted carbohydrate-active
      enzymes fell into 24 different enzymes classes, and up to eight different
      proteins within a same class are secreted. This indicates that fungal metabolism
      becomes oriented towards synthesis and secretion of a whole arsenal of enzymes
      able to digest almost the complete plant cell wall. Cellobiohydrolase is one of
      the only four proteins found both after growth on glucose and on plant cell wall
      and we propose that this enzyme could act as a sensor of the extracellular
      environment. Extensive knowledge of this very diverse F. graminearum exoproteome
      is an important step towards the full understanding of Fusarium/plants
      interactions.

PMID- 16283314
TI  - Differential gene expression during stationary phase between amicronucleates and
      micronucleates of the ciliated protist, Pseudourostyla cristata.
AB  - Ciliates are unicellular eukaryotic organisms with two types of nuclei, the
      'germline' micronucleus (MIC) and the 'somatic' macronucleus (MAC). We previously
      reported that when the MIC of Pseudourostyla cristata was eliminated by
      amputation, the resultant amicronucleate organisms exhibited a lower viability
      and abnormal oral structures. To gain insight into the genetic reorganization
      involved in or induced by removal of the MIC and the mechanism by which nuclear
      dimorphism was established, we investigated gene expression differences between
      amicronucleates and micronucleates, using suppression subtractive hybridization
      (SSH) techniques. Approximately 250 clones from each library were screened by
      cDNA array dot blotting. Altogether, 22 unique genes from the forward-subtractive
      library (micronucleates as tester, amicronucleates as driver) and 23 unique genes
      from the reverse-subtractive library (micronucleates as driver and
      amicronucleates as tester) were shown to be differentially expressed. These 45
      differentially expressed genes were found to be homologs of genes involved in
      various cellular processes including signal transduction, transcription, cell
      cycle accomplishment and general metabolism, cell structure, and stress response.
      We highlighted 14 genes, 7 that were unique from both the forward-subtractive and
      the reverse-subtractive libraries, using real time semi-quantitative RT-PCR. The
      characterization of these cDNAs represents a starting point in understanding the
      molecular mechanisms of amicronucleates disruption.

PMID- 16283318
TI  - Antioxidant status, lipid peroxidation and nitric oxide in fibromyalgia:
      etiologic and therapeutic concerns.
AB  - We proposed to assess the oxidant/antioxidant status, lipid peroxidation and
      nitric oxide (NO) in untreated fibromyalgia (FM) patients and controls. The
      effect of amitriptyline (A, 20 mg daily) and sertraline (S, 100 mg daily)
      treatment on patients' superoxide dismutase (SOD), xanthine oxidase (XO),
      adenosine deaminase (ADA) enzyme activities, thiobarbituric acid reactive
      substances (TBARS) and NO levels was investigated. Thirty female patients with
      primary FM and age-matched 16 healthy female controls were included. Patients
      received an 8-week course of treatment with either A or S. FM patients had higher
      serum levels of TBARS (particularly malondialdehyde) and lower levels of nitrite
      compared to controls whereas enzyme activities were similar. A and S
      significantly improved Fibromyalgia Impact Questionnaire (FIQ) pain scores,
      Hamilton anxiety and depression rating scales. But neither A nor S had
      significant effects on measured oxidative stress parameters, except SOD activity
      that was significantly reduced after S treatment. Total myalgic scores negatively
      correlated with XO activity, and depression scales negatively correlated with
      levels of TBARS. Our results indicate that patients with FM are under oxidative
      stress. These findings represent a rationale for further research assessing the
      effect of free radical scavengers or antioxidant agents like vitamins and omega-3
      fatty acids on peripheral and central mechanisms in FM.

PMID- 16283320
TI  - Superiority of alfacalcidol compared to vitamin D plus calcium in lumbar bone
      mineral density in postmenopausal osteoporosis.
AB  - In a randomized multicenter, double-blind, double-dummy, parallel group study a
      comparison of the efficacy and safety of 1 microg alfacalcidol to 880 IU vitamin
      D plus calcium carbonate (1 g calcium) once daily per os was performed on 148
      postmenopausal osteoporotic Caucasian patients with normal vitamin D serum levels
      for 18 months. Bone mineral density (BMD) was measured at baseline, 12 and 18
      months. Safety parameters were followed during the entire study period. Sixty
      nine (90.8%) in the alfacalcidol group and 67 (93.1%) in the vitamin D group were
      included in the ITT analysis. Lumbar BMD in the alfacalcidol group increased by
      0.017 g/cm2 (2.33%) and 0.021 g/cm2 (2.87%) from baseline (P<0.001) at 12 and 18
      months, respectively, whereas in the vitamin D plus calcium group the increase
      was 0.005 g/cm2 (0.70%) from baseline (N.S.) at both 12 and 18 months. The higher
      changes from baseline in the alfacalcidol group, as compared to the changes in
      the vitamin D plus calcium group at both 12 and 18 months, were found to be
      statistically significant (P=0.018, 0.005). A small increase of mean femoral BMD
      was achieved in both groups (N.S.). Adverse events were similar in both groups.
      No significant differences were noted between the groups in serum calcium. In
      conclusion, alfacalcidol was found to be superior in significantly increasing
      lumbar BMD as compared to vitamin D plus calcium while safety characteristics
      were found to be similar in both treatments.

PMID- 16283321
TI  - Pseudocalcification in a patient with inflammatory arthritis.

PMID- 16283319
TI  - Familial Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) is the most frequent hereditary inflammatory
      disease characterized by self-limited recurrent attacks of fever and serositis.
      It is transmitted in an autosomal recessive pattern and affects certain ethnic
      groups mainly Jews, Turks, Arabs, and Armenians. FMF is caused by mutations in
      MEFV gene, which encodes pyrin. This protein is expressed mainly in
      myeloid/monocytic cells and modulates IL-1beta processing, NF-kappaB activation,
      and apoptosis. A mutated pyrin probably results in uncontrolled inflammation. The
      most devastating complication of FMF is amyloidosis, leading to chronic renal
      failure. M694V homozygocity, male gender and the alpha/alpha genotype of serum
      amyloid A1 gene are the currently established risk factors for development of
      amyloidosis. Daily colchicine is the mainstay of the therapy for the disease,
      resulting in complete remission or marked reduction in the frequency and duration
      of attacks in most patients. It is also effective in preventing and arresting
      renal amyloidosis.

PMID- 16283322
TI  - Non-specific interstitial pneumonia; as the first clinical presentation of
      various collagen vascular disorders.
AB  - Recently, we have experienced significant numbers of patients diagnosed with non
      specific interstitial pneumonia (NSIP) by open lung biopsy or video-assisted
      thoracoscopic surgery. The purpose of this work was to describe the clinical
      features of patients with collagen vascular disorders (CVD) presenting NSIP in
      the absence of systemic involvement. This study also involved a retrospective
      review of patients with CVD presenting clinical and pathological evidence of NSIP
      in the absence of systemic manifestations of CVD. We found seven patients (six
      from our experience and one from literature review) with histologically proven
      NSIP who later developed typical CVD more than 6 months after the first
      presentation of NSIP. In these cases, it was difficult to speculate the
      development of CVD at the point of first presentation. Therefore, association of
      CVD should be considered in patients with NSIP even in the absence of classical
      systemic involvement.

PMID- 16283323
TI  - Dynamic multi-section CT imaging in acute myocardial infarction: preliminary
      animal experience.
AB  - To evaluate the feasibility of myocardial first-pass perfusion imaging with
      multidetector CT (MDCT). In five pigs, myocardial infarction was induced by
      permanent balloon occlusion of the left anterior descending coronary artery.
      Dynamic contrast-enhanced MDCT (12x1.5 mm, 120 kV, 30 mAs, 64 acquisitions, 40 ml
      iopromide 370@4 ml/s) and contrast-enhanced first-pass perfusion magnetic
      resonance (MR) imaging (TR 7.7 ms/TE 2.6 ms, 64 acquisitions, 0.05 mmol/kg Gd
      DTPA) were performed. Finally, the animals were sacrificed, and the heart was
      excised and stained with triphenyltetrazolin-chloride (TTC). Maximum signal
      intensity (SImax), contrast material arrival time (CAT), wash-in time (Tmax) and
      slope were calculated from time-density/signal-intensity curves. The area of
      myocardial hypoperfusion was measured as the percentage of the left-ventricular
      area (%LV). Parameters were compared using Bland-Altman plots and Student's t
      tests. The hypoperfused area on MDCT was 19.3+/-4.5%LV (MR imaging 17.2+/
      4.0%LV). The mean size of infarction was 18.7+/-5.7%LV with TTC. Semiquantitative
      analysis of MR imaging and MDCT for SImax, Tmax and slope showed significant
      differences between normal and infarcted myocardium (P<0.05). No significant
      differences were found for CAT. MDCT and MR imaging both allowed for the
      differentiation of hypoperfused and normal myocardium. Results given in absolute
      values differed significantly between both imaging modalities (P<0.05). MDCT has
      the potential for visual and semiquantitative assessment of first-pass myocardial
      perfusion.

PMID- 16283324
TI  - Intestinal oxalate absorption in patients with continent urinary diversion.
AB  - The objective of the study is to evaluate the post-operative effect of an
      orthotopic ileal neobladder or a Mainz pouch I bladder replacement on the extent
      of intestinal oxalate absorption. Gastrointestinal oxalate absorption was
      measured in six patients with an orthotopic ileal neobladder and in six patients
      with a Mainz pouch I bladder replacement. The function test applied was the
      [13C2]oxalate absorption test. With a range of 5.1-12.4%, the oxalate absorption
      of these patients was well within the reference range for healthy volunteers. The
      results from our small study indicate that such continent urinary diversions
      present no hazard for oxalate hyperabsorption and subsequent calcium oxalate
      urolithiasis.

PMID- 16283325
TI  - Oxalate and its handling in a low stone risk vs a stone-prone population group.
AB  - Despite hyperoxalurogenic eating habits relative to white subjects, South African
      blacks have urinary oxalate excretions, Tiselius risk indices (AP(CaOx)) and
      calcium oxalate saturations, which do not differ significantly from those of
      their white counterparts. The present study was undertaken to establish whether
      the BONN-Risk-Index (BRI) might discriminate between the urines of the two
      population groups and whether differences might exist in their respective
      gastrointestinal absorption rates of oxalate. Participants (n = 15 in each group)
      provided 24 h urines on their free diets for BRI determination. Gastrointestinal
      oxalate absorption was measured using the [13C2]oxalate absorption test. Results
      showed that BRI values were significantly lower in black subjects (2.04 vs 4.90,
      P = 0.034), but that there was no difference in the oxalate absorption between
      the groups (10.30 vs 9.95%, P = 0.87). These results suggest that South African
      black subjects handle dietary oxalate more efficaciously than white subjects and
      that this occurs via some endogenous mechanism, which has not yet been identified
      or characterized.

PMID- 16283326
TI  - Recent advances in nutritional research on urolithiasis.
AB  - Inappropriate dietary habits, overweight and lifestyle are suggested to
      contribute considerably to the increasing incidence and prevalence of
      urolithiasis. Numerous dietary factors can alter urinary composition and
      supersaturation, which can affect the process of stone formation. Dietary
      oxalate, calcium, protein, purines, sodium and ascorbic acid are known to be
      promoters of stone formation, whereas potassium and magnesium have been shown to
      be effective inhibitors. Although a high fluid supply has been demonstrated to
      decrease the incidence of urolithiasis, data from clinical and epidemiological
      studies on the effect of various beverages on the risk of urinary stone formation
      are conflicting. Continued research is warranted to clarify controversies
      concerning the impact of dietary calcium, oxalate, n-3 fatty acids, and phytate
      in calcium stone formation. Further randomized controlled studies should explore
      the long-term effects of dietary interventions in stone formers.

PMID- 16283328
TI  - The night-time temporal window of locomotor activity in the Namib Desert long
      distance wandering spider, Leucorchestris arenicola.
AB  - Even though being active exclusively after sunset, the male Leucorchestris
      arenicola spiders are able to return to their point of departure by following bee
      line routes of up to several hundreds of meters in length. While performing this
      kind of long-distance path integration they must rely on external cues to adjust
      for navigational errors. Many external cues which could be used by the spiders
      change dramatically or disappear altogether in the transition period from day to
      night. Hence, it is therefore imperative to know exactly when after sunset the
      spiders navigate in order to find out how they do it. To explore this question,
      we monitored their locomotor activity with data loggers equipped with infrared
      beam sensors. Our results show that the male spiders are most active in the
      period between the end and the beginning of the astronomical twilight period.
      Moreover, they prefer the moonless, i.e. darkest times at night. Hence, we
      conclude that the males are truly-and extremely-nocturnal. We further show that
      they are able to navigate under the very dim light conditions prevailing on
      moonless nights, and thus do not have to rely on the moon or on moon-related
      patterns of polarised light as potential compass cues.

PMID- 16283329
TI  - Ossicular differentiation of airborne and seismic stimuli in the Cape golden mole
      (Chrysochloris asiatica).
AB  - Comparison between the middle ear anatomy of the Cape golden mole (Chrysochloris
      asiatica), which exhibits a club-shaped malleus head, and the Desert golden mole
      (Eremitalpa granti), with a ball-shaped malleus head, suggests differences in
      sensitivity to airborne sound. Scanning laser Doppler vibrometric measurements of
      the ossicular behavior in response to both vibration and airborne sound were made
      in C. asiatica. Two distinct vibrational modes were observed. In response to low
      frequency vibration (70-200 Hz), the malleus oscillates about the ligament of the
      short process of the incus, whereas in response to high-frequency airborne sound
      (1-6 kHz) the ossicular chain rotates about the long axis of malleus. It is
      proposed that the club-shaped malleus head in C. asiatica constitutes an
      adaptation towards bimodal hearing-sensitivity to substrate vibrations and
      airborne sound. Possible functional differences between these two middle ear
      types are discussed.

PMID- 16283327
TI  - Nitric oxide/cGMP-mediated effects in the outflow region of the lower urinary
      tract--is there a basis for pharmacological targeting of cGMP?
AB  - Treatment with alpha-adrenoceptor antagonists that reduce the tone of prostatic
      stromal and urethral smooth muscle has beneficial effects in patients with benign
      prostatic hyperplasia (BPH) and lower urinary tracts symptoms (LUTS) and has
      brought attention to regulatory mechanisms of smooth muscle contractility of the
      outflow region. The prostate, urethra and bladder neck are densely supplied by
      nitric oxide (NO)-synthase-containing nerves that cause relaxation upon
      activation. In various experimental models, altered function or activity of the
      NO/cGMP pathway of the bladder neck and urethra may be related to inappropriate
      or un-coordinated functions of the bladder outlet and detrusor, but causal
      connections between alterations in this signaling system, a dysfunctional bladder
      outlet, and the development of LUTS are not established for humans. The present
      review focuses on regulatory functions of smooth muscle contractility by the
      NO/cGMP-pathway in the bladder neck, urethra, and prostate. Disease-related
      alterations in the NO/cGMP-pathway, and putative options for pharmacological
      modification of this signaling pathway in the out-flow region are briefly
      discussed.

PMID- 16283330
TI  - Hormonal correlates of reproductive status in the queenless ponerine ant,
      Streblognathus peetersi.
AB  - In colonies of the queenless ant Streblognathus peetersi, dominance interactions
      produce a reproductive hierarchy in which one individual, the alpha, is capable
      of producing offspring while her subordinates remain infertile. Based on
      differences between behaviour and cuticular hydrocarbon profiles, the
      subordinates can be further divided into high and low ranking workers. Although
      it had been shown previously that alphas treated with a juvenile hormone analog
      lose their reproductive status, little was known of the endocrinological basis of
      dominance in this species. To elucidate the underlying endocrinology of these
      three ranks, we measured the individual in vitro rate of juvenile hormone (JH)
      production of excised corpora allata, and the ecdysteroid titer of pooled
      hemolymph samples. Production of JH was highest in low-ranking workers,
      intermediate in high rankers, and almost undetectable in alphas. Ecdysteroid
      titers were low for low rankers, but were more than twice as high for both high
      rankers and alphas. The results support the hypothesis that JH suppresses ovarian
      function in these queenless ants, and suggest that ecdysteroids may be
      responsible for stimulating vitellogenin production. The possible role of these
      hormones as behavioural modulators is also discussed.

PMID- 16283331
TI  - Field metabolic rates of phytophagous bats: do pollination strategies of plants
      make life of nectar-feeders spin faster?
AB  - Recently, it was argued that extrinsic factors, such as high foraging costs, lead
      to elevated field metabolic rates (FMR). We tested this suggestion by comparing
      the FMR of nectar-feeding and fruit-eating bats. We hypothesized that the
      foraging effort per energy reward is higher for nectar-feeding mammals than for
      fruit-eating mammals, since energy rewards at flowering plants are smaller than
      those at fruiting plants. Using the doubly labelled water method, we measured the
      FMR of nectar-feeding Glossophaga commissarisi and fruit-eating Carollia
      brevicauda, which coexisted in the same rainforest habitat and shared the same
      daytime roosts. Mass-specific FMR of G. commissarisi exceeded that of C.
      brevicauda by a factor of almost two: 5.3+/-0.6 kJ g(-1) day(-1) for G.
      commissarisi and 2.8+/-0.4 kJ g(-1) day(-1) for C. brevicauda. Since nectar
      feeding bats imbibe nectar droplets of only 193 J energy content during each
      flower visit, a G. commissarisi bat has to perform several 100 flower visits per
      night to meet its energy requirement. The fruit-eating C. brevicauda, on the
      other hand, needs to harvest only 3-12 Piper infructescenses per night, as the
      energy reward per Piper equals ca. 6-30 kJ. We argue that the flowering and
      fruiting plants exert different selective forces on the foraging behaviour and
      energetics of pollinators and the seed dispersers, respectively. A comparison
      between nectar-feeding and non-nectar-feeding species in various vertebrate taxa
      demonstrates that pollinators have elevated FMRs.

PMID- 16283332
TI  - Physiological acclimation of a desert antelope, Arabian oryx (Oryx leucoryx), to
      long-term food and water restriction.
AB  - Desert mammals often experience scarcity of drinking water and food for prolonged
      periods. In this study, the first long-term acclimation experiment in a non
      domesticated desert-adapted ungulate, we investigated the mechanisms used by the
      Arabian oryx Oryx leucoryx, to adjust its physiology to progressive food and
      water restriction over 5 months, an experimental regimen and time course chosen
      to mimic what it typically experiences between spring and late summer in the
      desert. At the end of the acclimation period, oryx consumed less than one and
      half of food and water of animals in the control group and lost 8.2+/-2.6% of
      their initial body mass. Experimental animals reduced their mass-specific resting
      metabolic rate (RMR) and total evaporative water loss (TEWL) by 16.2 and 25.7%,
      respectively, and maintained a digestive efficiency of about 70%. We found no
      support for the idea that reduced RMR in oryx correlated with a decreased thyroid
      hormone concentration in plasma. At the end of the 5 months acclimation, oryx
      continued to mobilize fatty acids to fuel metabolism, and did not use protein
      breakdown as a major source of gluconeogenesis. Oryx in the experimental group
      reduced their water intake by 70% and maintained constant plasma osmolality. They
      adjusted their water budget by reducing mass-specific TEWL, increasing urine
      osmolality and reducing urine volume by 40%, and excreting feces with <50% water
      content. Oryx have an unusually low TEWL compared with other arid-zone ungulates;
      both hydrated and water-deprived individuals have TEWL values, 51.7 and 39.3%,
      respectively, of allometric predictions for arid-zone ungulates.

PMID- 16283333
TI  - Regulation of ventilation in the caiman (Caiman latirostris): effects of inspired
      CO2 on pulmonary and upper airway chemoreceptors.
AB  - In order to study the relative roles of receptors in the upper airways, lungs and
      systemic circulation in modulating the ventilatory response of caiman (Caiman
      latirostris) to inhaled CO2, gas mixtures of varying concentrations of CO2 were
      administered to animals breathing through an intact respiratory system, via a
      tracheal cannula by-passing the upper airways (before and after vagotomy), or via
      a cannula delivering gas to the upper airways alone. While increasing levels of
      hypercarbia led to a progressive increase in tidal volume in animals with intact
      respiratory systems (Series I), breathing frequency did not change until the CO2
      level reached 7%, at which time it decreased. Despite this, at the higher levels
      of hypercarbia, the net effect was a large and progressive increase in total
      ventilation. There were no associated changes in heart rate or arterial blood
      pressure. On return to air, there was an immediate change in breathing pattern;
      breathing frequency increased above air-breathing values, roughly to the same
      maximum level regardless of the level of CO2 the animal had been previously
      breathing, and tidal volume returned rapidly toward resting (baseline) values.
      Total ventilation slowly returned to air breathing values. Administration of CO2
      via different routes indicated that inhaled CO2 acted at both upper airway and
      pulmonary CO2-sensitive receptors to modify breathing pattern without inhibiting
      breathing overall. Our data suggest that in caiman, high levels of inspired CO2
      promote slow, deep breathing. This will decrease dead-space ventilation and may
      reduce stratification in the saccular portions of the lung.

PMID- 16283334
TI  - Proliferative response in necrotising enterocolitis is insufficient to prevent
      disease progression.
AB  - Necrotising enterocolitis (NEC) is characterised by severe mucosal loss and
      therefore gastrointestinal (GI) cell proliferation is essential for survival,
      epithelial repair and recovery of function. Trefoil peptides play a key role in
      epithelial restitution and repair, and we previously reported a down-regulation
      of these peptides in NEC. Oral administration of epidermal growth factor has a
      protective effect in a rat model of colitis. These observations raised the
      question of a link between the pathogenesis of NEC and decreased mucosal cell
      proliferation. This study investigates the pattern of mucosal cell proliferation
      in the GI tract of fetuses, normal neonatal controls, infants with NEC and those
      recovering from NEC. Parents of neonates up to 44 weeks' gestation undergoing
      laparotomy and bowel resection were approached for consent. Bowel samples from
      resection specimens, and GI tract extractions from products of conception at
      termination of pregnancy, were fixed in formalin and then embedded in paraffin
      blocks. Patterns of small and large bowel mucosal proliferation were assessed by
      immunohistochemical staining for Ki67. Seventeen foetal and 58 postnatal bowel
      samples [34 with NEC (22 acute, 12 recovery) and 24 controls] were analysed. The
      pattern of proliferation seen in the fetus and normal neonate was identical to
      that in mature bowel. In NEC severe mucosal necrosis was observed, but in viable
      crypts remaining, there was crypt hyperplasia and a relative increase in the
      proportion of cells staining positive for Ki67. In those patients recovering from
      NEC the pattern of proliferation was returning towards the normal range. In those
      patients with post-NEC strictures the recovery of normal bowel morphology was
      delayed. In NEC there is massive loss of potential proliferative tissue. The
      remaining viable tissue shows an increase in proliferative activity in the small
      and large bowel. Failure of rapid regeneration of functional mucosa may therefore
      be related to an inability of increased proliferative activity to match the
      losses from the surface; alternatively there may be rapid production of immature,
      short-lived cells. This study shows that the proliferative response, although
      present, is insufficient to rapidly reverse the mucosal insult observed in NEC.

PMID- 16283335
TI  - Exposure to carbon dioxide and helium reduces in vitro proliferation of pediatric
      tumor cells.
AB  - BACKGROUND: Minimally invasive techniques are increasingly applied to children
      with malignant tumors. We showed previously that CO(2) used for pneumoperitoneum
      modulates the function of macrophages and polymorphonuclear cells via direct
      effects and via acidification. Numerous in vitro and small animal model studies
      also confirmed an alteration of the behavior of several types of adult tumor
      cells by CO(2). The impact of CO(2) and other gases used for pneumoperitoneum on
      the behavior of various pediatric tumors has not yet been determined. METHODS:
      Cell lines of neuroblastoma (IMR 32, SK-N-SH, Sy5y), lymphoma (Daudi),
      hepatoblastoma (Huh 6), hepatocellular carcinoma (Hep G2), and rhabdomyosarcoma
      (Te 671) were incubated for 2 h. Incubation was performed with 100% CO(2), 100%
      helium, and 5% CO(2) as control. Cell proliferation was determined by the MTT
      assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] by actively
      growing cells to produce a blue formazan product. The MTT-assay was performed
      before, directly after incubation, and daily for 4 days. Vitality of the cells
      was determined by trypan blue. The extracellular pH during incubation was
      measured during gas exposition every 10 min using Bayer Rapid Lab 855. RESULTS:
      CO(2) for 2 h significantly decreased the proliferation of neuroblastoma,
      lymphoma, hepatoblastoma, and hepatocellular carcinoma cells. This decrease
      persisted over 4 days in neuroblastoma, lymphoma, and hepatocellular carcinoma
      cells. The CO(2) had no impact on hepatoblastoma and rhabdomyosarcoma cells.
      Helium had a similar effect on neuroblastoma cells. After 4 days, a significant
      decrease of cell activity was found in two neuroblastoma cell lines and in
      hepatoblastoma cells. Helium had no effect on lymphoma and hepatocellular
      carcinoma cells. The extracellular pH was 6.2 during incubation with CO(2), and
      7.6 during incubation with helium. CONCLUSION: CO(2) and helium may affect the
      proliferation of some pediatric tumor cell lines in vitro. However, some of these
      effects and the impact on the extracellular pH are differential. The role of pH
      modulation, hypoxia and direct effects of gases remain to be investigated before
      a general recommendation on the use of minimally invasive techniques in pediatric
      oncology can be given.

PMID- 16283336
TI  - Elevated serum nitric oxide metabolites in biliary atresia.
AB  - Biliary atresia (BA) remains one of the most intractable liver diseases in
      children. The aim of this study was to investigate the possible roles of nitric
      oxide (NO) in BA. Serum levels of nitrite and nitrate (NO production) were
      determined using a colorimetric method from 65 post-operative BA patients and 12
      healthy children. The patients were categorized into two groups according to
      their jaundice status, and serum alanine aminotransferase (ALT, a marker for
      liver injury). Unpaired t tests were used. Data are expressed as mean and SD in
      terms of mumol/l. Age and gender between BA patients and controls were
      comparable. Serum NO metabolites of BA patients was higher than the controls
      (79.77+/-21.22 vs. 65.75+/-9.44, P=0.001). Subgroup analysis revealed that there
      was no difference in serum nitrate/nitrite levels of BA patients without jaundice
      compared to those with jaundice (78.85+/-23.23 vs. 80.90+/-18.76, P=0.70).
      However, patients with serum ALT> or =100 IU/l had higher levels of serum NO
      metabolites compared to those with serum ALT<100 IU/l. In conclusion, NO
      production was elevated in BA patients compared to normal controls. Serum NO was
      associated with serum ALT levels, but not with jaundice status, in BA patients.
      These suggest that NO plays a role in the pathophysiology of liver injury in post
      operative BA.

PMID- 16283337
TI  - Effect of diclofenac on germ cell apoptosis following testicular ischemia
      reperfusion injury in a rat.
AB  - Recent evidence suggests that enhanced cell apoptosis is responsible for germ
      cell loss following testicular ischemia-reperfusion (IR) injury. A nonsteroidal
      anti-inflammatory drug diclofenac sodium (Voltaren) is a prostaglandin-synthesis
      inhibitor, which is widely used in many testicular disorders. The purpose of the
      present study was to examine the effect of diclofenac (DIC) on germ cell
      apoptosis in the ischemic and contralateral testes following testicular IR in a
      rat. Forty rats were divided randomly into four experimental groups of ten rats
      each: group A (Sham)-Sham operated animals; group B (Sham-DIC)-Sham operated rats
      that were treated with DIC given subcutaneously at a dose of 10 mg/kg, once
      daily, 24, 48 and 72 h following operation; group C (IR) underwent 90 min of
      unilateral testicular IR; group D (IR-DIC)-rats underwent 90 min of unilateral
      testicular IR and were treated with DIC similarly to group B. Ninety-six hours
      following operation, the rats were sacrificed and testes were harvested.
      Johnsen's criteria and the number of germinal cell layers were used to categorize
      the spermatogenesis. TUNEL assay was used to determine germ cell apoptosis in
      both the ischemic and contralateral testes. Statistical analysis was performed
      using the non-parametric Kruskal-Wallis ANOVA test, with P less than 0.05
      considered statistically significant. Testicular ischemia in rats led to
      histological damage in the ipsilateral testis. In the contralateral testis,
      minimal damage was observed. Germ cell apoptosis in both the ischemic and the
      contralateral testes increased significantly after IR. Treatment with DIC did not
      change histologic parameters of spermatogenesis in both the ischemic and
      contralateral testes, but decreased germ cell apoptosis in both testes following
      testicular IR. We conclude that testicular ischemia causes an increase in germ
      cell apoptosis in the contralateral testis. Diclofenac may be beneficial for
      spermatogenesis following testicular IR by decreasing germ cell apoptosis.

PMID- 16283338
TI  - Combined ileal heterotopic pancreatic and gastric tissues causing ileocolic
      intussusception in an infant.
AB  - Pathological intussusception is rare in infancy with Meckel's diverticulum being
      the most common lesion. Isolated heterotopic pancreatic tissue in the serosa of
      the ileum causing intussusception is extremely rare. We report a case of ileal
      heterotopic pancreatic tissue associated with ectopic gastric mucosa causing
      ileocolic intussusception in an infant, with review of the literature.

PMID- 16283339
TI  - "Fast-track" rehabilitation after rectal cancer resection.
AB  - BACKGROUND AND AIMS: After rectal cancer surgery, postoperative general
      complications occur in 25-35% of all patients and postoperative hospital stay is
      14-21 days. "Fast-track" rehabilitation has been shown to accelerate recovery,
      reduce general morbidity and decrease hospital stay after elective colonic
      surgery. Because the feasibility of "fast-track" rehabilitation in patients
      undergoing rectal cancer surgery has not been demonstrated yet, we demonstrate
      our initial results of "fast-track" rectal cancer surgery. PATIENTS AND METHODS:
      Seventy consecutive unselected patients undergoing rectal cancer resection by one
      surgeon underwent a perioperative "fast-track" rehabilitation. Demographic and
      operative data, pulmonary function, pain and fatigue, local and general
      complications and mortality were assessed prospectively. RESULTS AND FINDINGS:
      Thirty-six female and 34 male patients aged 65 (34-77) years underwent open
      (n=31) or laparoscopic (n=39) anterior resection with partial mesorectal excision
      (PME 27), anterior resection with total mesorectal excision and protective loop
      ileostomy (TME 29) or abdominoperineal excision with colostomy (APR 14). Overall,
      pulmonary function returned to >80% of preoperative value on day 2 (1-4) and the
      first bowel movement occurred on day 1 (0-3) after surgery. The incidence of
      local and general complications was 27 and 18%, respectively. Postoperative
      hospital stay was 8 (3-50) days overall, but shorter after PME [5 (3-47)] than
      TME [10 (5-42)] or APR [9 (5-50)] (p<0.01). INTERPRETATION AND CONCLUSION: "Fast
      track" rehabilitation was feasible in patients undergoing rectal cancer
      resection. Local morbidity was not increased, while general morbidity and
      postoperative hospital stay compared favourably to other series with
      "traditional" perioperative care.

PMID- 16283340
TI  - Reduction of miss rates of colonic adenomas by zoom chromoendoscopy.
AB  - BACKGROUND AND AIMS: The aim of this study was to determine the detection rate of
      polyps using zoom chromoendoscopy (ZE) compared with standard video colonoscopy.
      PATIENTS AND METHODS: End-to-end colonoscopies were performed in 50 patients by
      two different endoscopists blinded for each other's results. Lesions detected
      during initial standard colonoscopy (C1) were biopsied or removed by snare
      resection. The second colonoscopy (C2) was done with a zoom colonoscope spraying
      the whole colon with indigocarmine (0.4%). In addition, detected mucosal lesions
      were documented prior to ZE and then classified according to the pit pattern
      classification before biopsy or removal. The retrieval time for each procedure
      was determined. RESULTS: The average retrieval time for C1 was 13+/-9 min (9-24)
      and 28+/-11 min (16-38, p<0.05) for ZE. During C1, 56 lesions were detected in 26
      of 50 patients (34 hyperplastic and 22 adenomatous). During C2, 19 additional
      polyps were documented prior to ZE (15% tandem miss rate), and 20 further lesions
      were detected with ZE (21% additional polyp detection rate compared to C1 and C2
      without ZE). Of the 39 additional lesions removed during C2 after ZE, 29 were
      hyperplastic and 10 were adenomatous. Most adenomas detected during the second
      investigation were found in patients in whom adenomatous polyps had already been
      removed during the initial colonoscopy (9 of 26 patients vs 1 of 24 patients,
      p<0.02). No carcinoma was detected. The pit pattern classification allowed a
      correct differentiation between hyperplastic and adenomatous polyps (accuracy
      93%, sensitivity 90%, specificity 97%). CONCLUSION: Using zoom chromoendoscopy,
      the rate of detecting colonic polyps can be increased at the cost of a longer
      retrieval time.

PMID- 16283341
TI  - A novel treatment of grade III acromioclavicular joint dislocations with a C-hook
      implant.
AB  - INTRODUCTION: This study evaluates the results of the new surgical treatment of
      complete acromioclavicular (ac) dislocations using coracoclavicular (cc) fixation
      with a shape memory metal C-hook implant. MATERIALS AND METHODS: Fifteen patients
      were prospectively analyzed. They all had a Tossy III ac dislocation due to
      trauma. The ac ligament was reinserted using a surgical bone anchor, and the
      position of the joint was restored by fixing it with a C-hook. After 3 months the
      C-hook was removed. Functional status, symptom severity, X-rays and patient
      satisfaction were analyzed during clinical control visits. The follow-up time was
      1 year. RESULTS: At 12 weeks, full shoulder function had been achieved by 93% of
      the patients. The final control visit showed full recovery of active ROM in all
      patients. Two patients had mild pain during certain movements. X-rays showed the
      precise anatomical position of ac joint with no statistically significant
      differences compared to the healthy side. Patient contentment was excellent in 14
      cases and satisfactory in one case. The average sick-leave was 58 days, including
      the removal operation. Minor osteolysis of the clavicle was noticed in two
      patients. CONCLUSION: The new C-hook implant provides accurate anatomical
      reduction, conserves the articular surfaces and enables fast functional recovery
      with excellent patient contentment. Technically, the implant is easy to use.
      Based on this study, the C-hook presents a reliable novel treatment option in
      surgical ac repair.

PMID- 16283342
TI  - Ponseti technique for the correction of idiopathic clubfeet presenting up to 1
      year of age. A preliminary study in children with untreated or complex
      deformities.
AB  - INTRODUCTION: The aim of this study is to evaluate the effectiveness of the
      Ponseti method in children presenting before 1 year of age with either untreated
      or complex (initially treated unsuccessfully by other conservative methods)
      idiopathic clubfeet. PATIENTS AND METHODS: The authors report 134 feet of 92
      patients with Dimeglio grade 2, 3, or 4 deformities treated with the Ponseti
      method. Twenty-four percent of feet were of complex deformities at initial
      presentation to the authors' clinics. RESULTS: At a mean follow-up of 46 months
      (range 24-89) we avoided joint release surgery in 97% of feet. Sixty-seven
      percent required a percutaneous tenotomy of the Achilles tendon. Relapse rate was
      31% (41 feet). We treated 2 relapses by restarting the use of orthosis, 17 with
      re-casting, 18 with anterior tibial tendon transfer following a second relapse,
      and 4 feet with extensive joint surgery. Compliance with the use of orthosis was
      identified as the most important risk factor (P<0.0001) for relapses. Previous
      unsuccessful treatment attempts by other conservative methods did not adversely
      affect the results unless the cases had iatrogenic deformities. Cases with
      iatrogenic deformities from previous treatment had a significantly increased risk
      of non-compliance and relapse. Experience of the treating surgeon and cast
      complications were also related to relapses. CONCLUSION: Our results show that
      the Ponseti technique is reproducible and effective in children at least up to 12
      months of age. It can also produce good correction in children presenting with
      complex idiopathic deformities. Therefore, extensive joint releases should not be
      considered immediately in such cases. The treating surgeon should be meticulous
      in using the technique and ensure compliance to foot abduction brace in order to
      avoid recurrences.

PMID- 16283343
TI  - Long-term results of the metal-cancellous cementless Lubeck total hip
      arthroplasty: a critical review at 12.8 years.
AB  - INTRODUCTION: The influence of a spongy metal surface total hip arthroplasty
      (THA) (S&G, ESKA, Lubeck, Germany) on the clinical, psychometric, and radiograhic
      long-term results were examined. MATERIAL AND METHODS: An amount of 137 THA with
      the cementless spongy metal Lubeck hip prosthesis were evaluated long-term,
      radiographically and clinically, with a mean follow-up time of 12.8 years (range
      10.1-14.9 years). The MOS SF-36 was used to assess the health-related quality of
      life (HRQL). RESULTS: Cumulative survival rates were 90% (+/-8%) for the cups and
      86% (+/-5%) for the stems at 14.9 years. Four stems fractured at the middle part
      (3%) without major trauma. In the remaining patients the clinical results
      expressed as Harris Hip Score (HHS) averaged 88 (range 34-100). Patients above 60
      years undergoing THA had no significant difference in HRQL (MOS SF-36) in
      comparison to the age-matched healthy population (P>0.05). Patients younger than
      60 years had scores lower than normal in the physical function domains (P<0.01),
      but were comparable in the mental health domains (P>0.05). Radiolucent lines and
      bone atrophy related to stress shielding by distal fixation were found in the
      periprosthetic Gruen Zone I (19.8, 16.8%) and VII (10.3, 27.1%) of the proximal
      femur. DISCUSSION: Whereas the rate of aseptic cup failures of the cementless
      spongy metal Lubeck hip prosthesis is among the best, the failure rate of the
      stems is attributable to osteolysis of the proximal femur. The fractures of the
      stem may be attributed to the combination of the lack of proximal support, the
      fully porous stem made of a cast cobalt-chrome-molybdenum alloy, and the narrow
      dimension of the stem core. The long-term results of the spongy metal cup are
      good, whereas the high loosening and fracture rate of fully coated stem are a
      source of concern especially with regard to the difficult revision scenario with
      frequent massive bone loss.

PMID- 16283344
TI  - Evaluation of the association between null genotypes of glutathione-S
      transferases and Behcet's disease.
AB  - Glutathione S-transferases (GST) play an important role in oxidative stress
      related syndromes. An imbalance of the oxidant and antioxidant systems is
      important in the pathogenesis of Behcet's disease (BD). The objective of this
      study was to evaluate the association of null genotypes of GST-M1 and GST-T1 with
      BD since some preliminary molecular genetic data were recently published. Ninety
      four Turkish BD patients (42 male, 52 female, 37.1+/-10.4 years) and 140 healthy
      volunteers (70 male, 70 female, 36.8+/-11.7 years) matched for age and gender
      with the patients as the control group were included in the study. Distributions
      of GST-M1 and GST-T1 genotypes were determined by multiplexed PCR using three
      sets of primers for GST-M1, GST-T1, and beta-globulin genes. There was no
      association between BD and the frequencies of GST-M1 and GST-T1 null genotypes
      when compared to controls by separate analysis. However, by cross and pooled
      combination analysis there was a significant association between the frequencies
      of pooled GSTs with one or both null genotypes in BD and controls. This is the
      first evidence that the association between the frequencies of GST-M1 and GST-T1
      null genotypes and BD might be dependent on the interaction of multiple null
      allele polymorphisms rather than a single null allele of GST-M1 and GST-T1.

PMID- 16283345
TI  - Histopathological and immunohistochemical studies of poroid hidradenoma.
AB  - Poroid hidradenoma (PH), a less common subtype of poroid neoplasm (PN) than
      eccrine poroma (EP), has not been immunohistochemically studied before. Six cases
      of PH (four solitary PH and two PH coexisted with other types of PN) were
      included in the study. Fifteen cases of EP were also included for comparison.
      Hematoxylin and eosin, Masson-Zimmerman silver stain, and a variety of
      immunohistochemical stains were used. Microscopically, PH is not connected to the
      epidermis. All six PH contained small poroid cells and larger, paler cuticular
      cells. Some PH showed separate or clusters of sebocytes (2/6), horn cysts (1/6),
      juxtaposed lymphoid follicles in the stroma (1/6) and foci of keratohyaline
      granules (2/6), none of which was seen in the 15 EP. Immunohistochemically, the
      keratin distribution of PH was very similar to that of EP. PH has a very small
      number of Langerhans cells (significantly lower than the overlying epidermis,
      P=0.045), and a sparse deposition of melanin. We conclude that except the
      location, the histopathological and immunochemical differences between PH and EP
      were small. Sebaceous differentiation in two PH lesions suggested the possibility
      of an apocrine origin. The deeper parts of eccrine apparatus other than basaloid
      cells may have been more actively involved in the histogenesis of PH.

PMID- 16283346
TI  - Toll-like receptor 2 (TLR2) mediates intracellular signalling in human
      keratinocytes in response to Malassezia furfur.
AB  - Toll-like receptors (TLRs) are crucial players in the innate immune response to
      microbial invaders. The lipophilic yeast Malassezia furfur has been implicated in
      the triggering of scalp lesions in psoriasis. The aim of the present study was to
      assess the role of TLRs in the defence against M. furfur infection. The
      expression of the myeloid differentiation factor 88 (MyD88) gene, which is
      involved in the signalling pathway of many TLRs, was also analysed. In addition,
      a possible correlation of antimicrobial peptides of the beta-defensin family to
      TLRs was tested. Human keratinocytes infected with M. furfur and a variety of M.
      furfur-positive psoriatic skin biopsies were analysed by RT-PCR, for TLRs, MyD88,
      human beta-defensin 2 (HBD-2), HBD-3 and interleukin-8 (IL-8) mRNA expression.
      When keratinocytes were infected with M. furfur, an up-regulation for TLR2,
      MyD88, HBD-2, HBD-3 and IL-8 mRNA was demonstrated, compared to the untreated
      cells. The same results were obtained when psoriatic skin biopsies were analysed.
      The M. furfur-induced increase in HBD-2 and IL-8 gene expression is inhibited by
      anti-TLR2 neutralising antibodies, suggesting that TLR2 is involved in the M.
      furfur-induced expression of these molecules. These findings suggest the
      importance of TLRs in skin protection against fungi and the importance of
      keratinocytes as a component of innate immunity.

PMID- 16283348
TI  - RBE of quasi-monoenergetic 60 MeV neutron radiation for induction of dicentric
      chromosomes in human lymphocytes.
AB  - The production of dicentric chromosomes in human lymphocytes by high-energy
      neutron radiation was studied using a quasi-monoenergetic 60 MeV neutron beam.
      The average yield coefficient [see text] of the linear dose-response relationship
      for dicentric chromosomes was measured to be (0.146+/-0.016) Gy-1. This confirms
      our earlier observations that above 400 keV, the yield of dicentric chromosomes
      decreases with increasing neutron energy. Using the linear-quadratic dose
      response relationship for dicentric chromosomes established in blood of the same
      donor for 60Co gamma-rays as a reference radiation, an average maximum low-dose
      RBE (RBEM) of 14+/-4 for 60 MeV quasi-monoenergetic neutrons with a dose-weighted
      average energy [see text] of 41.0 MeV is obtained. A correction procedure was
      applied, to account for the low-energy continuum of the quasi-monoenergetic
      spectral neutron distribution, and the yield coefficient alpha for 60 MeV
      neutrons was determined from the measured average yield coefficient [see text].
      For alpha, a value of (0.115+/-0.026) Gy-1 was obtained corresponding to an RBEM
      of 11+/-4. The present experiments extend earlier investigations with
      monoenergetic neutrons to higher energies.

PMID- 16283349
TI  - Thoron levels in traditional Chinese residential dwellings.
AB  - A survey on radon (222Rn), thoron (220Rn) and its decay products (220RnD) was
      conducted in Chinese traditional residential dwellings constructed with loam
      bricks or soil wall. The activity concentrations in 164 dwellings under
      investigation were 72.4+/-59.2 (arithmetic mean, AM) and 57.5+/-2.0 Bq m-3
      (geometric mean, GM) for 222Rn, and 318+/-368 and 162+/-3.7 Bq m-3 for 220Rn,
      respectively. For 220RnD, 67 dwellings were studied. The AM of the 220RnD
      equilibrium equivalent concentration was 3.8+/-3.3 Bq m-3 with a maximum value of
      15.8 Bq m-3. On the basis of these results, the average annual effective doses to
      the local residents due to radon and thoron exposure were 1.44-4.62 mSv. Thoron
      contributes 12.9-56.6% to the total doses. Preliminary results show that there is
      a relation between 220RnD in air and 232Th in soil. The correlation factors of
      outdoor and indoor were 0.88 and 0.40. The 232Th activity content of Chinese soil
      is estimated to be about two times the world average. The traditional residential
      dwellings with soil construction are still common in China. Further
      investigations on the 220Rn level in these dwelling with the aim of dose
      reduction are proposed.

PMID- 16283350
TI  - delta-Storage pool disease: a pitfall in the forensic investigation of sudden
      anal blood loss in children: a case report.
AB  - We present the case of a 3.5-year-old boy with sudden anal blood loss at school.
      Sexual abuse was suspected, and, apart from anal fissures seen on sigmoidoscopy,
      no other clinical signs of any sort of disorder were present. As no medical
      explanation for the blood loss could be given, penetrating anal trauma was
      suggested. During follow-up consultations, there were complaints of occasional
      blood loss. Platelet aggregation tests and electron microscopy finally helped
      diagnose a delta-storage pool disease which is a rare haemostatic disorder
      involving the dense granules of the platelets. Although exclusion of well-known
      blood diseases through routine laboratory testing is a common practice in
      children with sudden blood loss, this case illustrates the value of more
      specialised investigation both from a diagnostic and forensic point of view.

PMID- 16283351
TI  - Short amplicon STR multiplex for stain typing.
AB  - We developed a short tandem repeat (STR) typing kit based on DNA database systems
      that are included in, for example, the Interpol Standard Set of Loci
      recommendations (i.e., TH01, VWA, D3S1358, FGA) and the gender typing system
      Amelogenin. Two different multiplex sets were tested using the fluorescent dyes
      FAM, JOE, and VIC. The PCR results were compared to the commercially available
      AmpFISTR Blue kit, which contains the STRs D3S1358, VWA, and FGA. The advantage
      of our multiplex compared with the Blue kit was the generation of shorter
      amplicons (<200 bp) and the higher combined power of discrimination.

PMID- 16283352
TI  - Age estimation in children by measurement of open apices in teeth.
AB  - This paper concerns a method for estimating the age of children based on their
      teeth. The sample consisted of 455 Italian white children (213 boys, 242 girls)
      aged between 5 and 15 years. The purpose of the present investigation was to
      present a method for assessing chronological age based on the relationship
      between age and measurement of the open apices in teeth. Pearson's correlation
      coefficients between age and these variables showed that the correlations between
      age and the open apices in teeth were significant and negative. Furthermore,
      gender and the number of teeth with the apical end of the root canals completely
      closed (N(0)) showed a significant correlation with chronological age. With the
      aid of a stepwise multiple regression model, a linear relationship between open
      apices, N(0), and age was shown. Statistical analysis indicated that these
      morphological variables explain 83.6% of the variations in estimated
      chronological age. The median of residual errors between the actual and estimated
      ages was -0.035 years [interquartile range (IQR)=1.18 years].

PMID- 16283353
TI  - Visualization of non-heme ferric and ferrous iron by highly sensitive non-heme
      iron histochemistry in the stress-induced acute gastric lesions in the rat.
AB  - Redox-active non-heme iron catalyzes hydroxyl radical [Formula: see text]
      generation through Haber-Weiss reaction. Oxidative tissue damage by OH* has been
      suggested in the development of stress-induced gastric lesion. Using highly
      sensitive non-heme iron histochemistry, the perfusion-Perls and -Turnbull methods
      plus DAB intensification, we studied the distribution of non-heme ferric and
      ferrous iron (NHF[III] and NHF[II]) in the normal stomach and its changes in the
      acute gastric lesions induced by restraint water immersion (RWI) stress in the
      rat. Both NHF[III] and NHF[II] staining increased in the oncotic parietal cells
      located at the erosive lesion which developed on the gastric mucosal folds after
      3 h RWI. It was considered that increase in non-heme iron in these cells
      catalyzed OH* generation under the presence of O(2)(*-) released from abundant
      injured mitochondria. This was supported by the increase in H(2)O(2) staining in
      the erosive region and the obvious reduction of the gastric lesion following
      administration of deferoxamine before RWI. NHF[II] was stained in the arterial
      endothelium in the tela submucosa of the normal gastric wall and increase in the
      entire gastric mucosa after 3 h RWI suggests that the changes in the vascular non
      heme iron metabolism were also involved in the response of the stomach to
      stressful conditions.

PMID- 16283354
TI  - Intranuclear microtubules are hallmarks of an unusual form of cell death in
      cisplatin-treated C6 glioma cells.
AB  - We describe an unusual form of non-accidental cell death marked by ectopic
      microtubules in the nucleus of a subpopulation of cisplatin-treated C6 glioma
      astrocytes in culture. At electron microscopy, the perinuclear condensed
      chromatin did not completely adhere to the nuclear envelope of these cells being
      separated by single or loosely bundled 20-nm-thick microtubules located in an
      electron-lucid slit-like zone; the presence of alpha-tubulin lining the inner
      membrane of the nuclear envelope was confirmed by immunolabeling at confocal
      microscopy. Since tufts of microfilaments-like fibers also occurred in their
      central nuclear areas, these cells are referred to as CIMMs (Cells with
      Intranuclear Microtubules and Microfilaments). The nuclear reorganization of
      CIMMs also involved nucleolar segregation and formation of heterogeneous ectopic
      ribonucleoprotein (RNP)-derived structures, indicating disruption of the RNP
      based transcription machinery. The cytoplasmic organelles of CIMMs were
      structurally intact, and propidium iodide did not accumulate intracellularly
      under vital conditions while the plasma membrane was often Annexin V-positive.
      All these findings suggest that CIMMs were lethally damaged and committed to an
      atypical programmed cell death resembling early apoptosis (this is also supported
      by the presence of a limited number of TUNEL-positive CIMMs). CIMMs appeared well
      before the main cisplatin-induced cycling arrest of the cell population (G2/M
      block at 72 h) and had mostly G1 DNA content: this suggests that they may
      represent the cohort of cells which passed cisplatin-altered mitoses with
      intranuclear retention of microtubules from an incompletely disassembled mitotic
      spindle.

PMID- 16283355
TI  - Regulation of Toll-like receptor 4 expression in mouse colon by macrophage
      migration inhibitory factor.
AB  - Recent studies have indicated that macrophage migration inhibitory factor (MIF)
      and Toll-like receptor (TLR) play an important role in the regulation of innate
      immune responses. In this study, we investigated the effect of MIF on the
      expression of TLR4, a receptor that recognizes lipopolysaccharide, in colon using
      MIF-deficient mice. TLR4 mRNA expression in the colon tissues was determined by
      northern blot analysis. Western blot analysis and immunohistochemistry in the
      colon tissues were performed to evaluate the expression of TLR4 protein. The
      expressions of TLR4 mRNA and protein were remarkably down-regulated in colon
      tissues of MIF-deficient mice compared with wild-type mice and up-regulated by
      treatment with recombinant MIF. Immunohistochemical study revealed the presence
      of TLR4-positive staining in mononuclear cells in the lamina propria and
      intraepithelial mononuclear cells as well as weak staining in epithelial cells
      and crypts in colon tissues of wild-type mice. In contrast, MIF-deficient mice
      did not show TLR4-positive staining in the colonic mucosa. In MIF-deficient mice
      injected with recombinant mouse MIF (rMIF), TLR4-positive staining cells were
      observed in colon tissues similar to the findings in wild-type mice.
      Administration of dextran sulfate sodium (DSS) up-regulated the expression of
      TLR4 in the colons of WT mice but not in those of MIF-deficient mice.
      Furthermore, pretreatment with rMIF up-regulated the expression of TLR4 in
      response to DSS in MIF-deficient mice. Our results suggest that MIF affects the
      expression of TLR4 in mouse colon under both normal and colitic conditions.

PMID- 16283356
TI  - Truncated HP1 lacking a functional chromodomain induces heterochromatinization
      upon in vivo targeting.
AB  - Packaging of the eukaryotic genome into higher order chromatin structures is
      tightly related to gene expression. Pericentromeric heterochromatin is typified
      by accumulations of heterochromatin protein 1 (HP1), methylation of histone H3 at
      lysine 9 (MeH3K9) and global histone deacetylation. HP1 interacts with chromatin
      by binding to MeH3K9 through the chromodomain (CD). HP1 dimerizes with itself and
      binds a variety of proteins through its chromoshadow domain. We have analyzed at
      the single cell level whether HP1 lacking its functional CD is able to induce
      heterochromatinization in vivo. We used a lac-operator array-based system in
      mammalian cells to target EGFP-lac repressor tagged truncated HP1alpha and
      HP1beta to a lac operator containing gene-amplified chromosome region in living
      cells. After targeting truncated HP1alpha or HP1beta we observe enhanced tri
      MeH3K9 and recruitment of endogenous HP1alpha and HP1beta to the chromosome
      region. We show that CD-less HP1alpha can induce chromatin condensation, whereas
      the effect of truncated HP1beta is less pronounced. Our results demonstrate that
      after lac repressor-mediated targeting, HP1alpha and HP1beta without a functional
      CD are able to induce heterochromatinization.

PMID- 16283357
TI  - Neurochemical characterisation of sensory receptors in airway smooth muscle:
      comparison with pulmonary neuroepithelial bodies.
AB  - Descriptions of morphologically well-defined sensory airway receptors are sparse,
      in contrast to the multiplicity of airway receptors that have been identified
      electrophysiologically. The present study aimed at further determining the
      location, morphology and neurochemical coding of subepithelial receptor-like
      structures that have been sporadically reported in the wall of large diameter
      airways. The results were compared with those obtained for pulmonary
      neuroepithelial bodies (NEBs), which are complex intraepithelial sensory airway
      receptors. Multiple immunocytochemical staining showed branching laminar
      subepithelial receptor-like endings, which were found to intercalate in the
      smooth muscle layer of intrapulmonary conducting airways in rats. Because of the
      consistent intimate association with the airway smooth muscle, the laminar
      terminals will further be referred to as 'smooth muscle-associated airway
      receptors (SMARs)'. SMARs were characterised by their Na(+)/K(+)-ATPase alpha3,
      vesicular glutamate transporter 1 (VGLUT1) and VGLUT2-immunoreactivity,
      expression of the ATP receptor P2X(3), and the presence of calcium-binding
      proteins. Nerve fibres giving rise to SMARs were shown to be myelinated and to
      have a vagal origin. Interestingly, the neurochemical coding and receptor-like
      appearance of SMARs appeared to be almost identical to at least part of the
      complex vagal sensory terminals in NEBs. Intraepithelial nerve endings in
      pulmonary NEBs were indeed also shown to originate from myelinated vagal afferent
      nerve fibres, and to express Na(+)/K(+)-ATPase alpha3, VGLUT1, VGLUT2, P2X(3) and
      calcium-binding proteins. Since several of the latter proteins have been reported
      as markers for mechanoreceptor terminals in other organs, both SMARs and the
      vagal nodose nerve terminals in NEBs seem good candidates to represent the
      morphological counterparts of at least subsets of the extensive population of
      physiologically characterised myelinated vagal airway mechanoreceptors. The
      observation that SMARs and NEBs are regularly found in each other's immediate
      neighbourhood, and the very similar characteristics of their nerve terminals,
      point out that the interpretation of electrophysiological data based on 'local'
      stimuli should be made with great caution.

PMID- 16283359
TI  - Distribution of junction- and differentiation-related proteins in urothelial
      cells at the leading edge of primary explant outgrowths.
AB  - Leading edge cells, which are located at the forefront of a wound margin, play a
      significant role in coordinating the wound healing process. In this study,
      leading edge cells of the urothelial explant outgrowth, resembling leading edge
      cells during urothelial full-thickness wound healing in vivo, were analyzed for
      expression and distribution of junction and differentiation-related proteins.
      Ultrastructural and immunofluorescence studies revealed that urothelial cells at
      the leading edge expressed ZO-1, claudin-4, occludin, E-cadherin, cytokeratin 7
      and cytokeratin 20, while no expression of claudin-8 was noted. ZO-1, claudin-4,
      occludin and E-cadherin were localized along the cell membranes where
      neighbouring leading edge cells were in contact. Cytokeratin 7 was detected as
      filaments and cytokeratin 20 as small dots and sparse filaments. In conclusion,
      we detected early expression of ZO-1, claudin-4 and occludin at the urothelial
      leading edge, predicating the later formation of tight junctions as a necessary
      stage for the differentiation process that subsequently begins. The expression of
      occludin and cytokeratin 20 in urothelial cells at the leading edge suggests that
      leading edge cells may develop into fully differentiated superficial cells.

PMID- 16283358
TI  - Recent progress in histochemistry and cell biology: the state of the art 2005.
AB  - Advances in the field of histochemistry, a multidisciplinary area including the
      detection, localization and functional characterization of molecules in single
      cells and complex tissues, often drives the attainment of new knowledge in the
      broadly defined discipline of cell biology. These two disciplines, histochemistry
      and cell biology, have been joined in this journal to facilitate the flow of
      information with celerity from technical advancement in histochemical procedures,
      to their utilization in experimental models. This review summarizes advancements
      in these fields during the past year.

PMID- 16283360
TI  - Expression profile of genes related to osteoclastogenesis in mouse growth plate
      and articular cartilage.
AB  - Based on developmental fate and function, cartilage tissue is broadly classified
      into transient cartilage (e.g. growth plate, GP) and permanent cartilage (e.g.
      articular cartilage, AC). The former eventually disappears and is replaced by
      bone during the endochondral ossification process, whereas the latter retains its
      permanency. Osteo(chondro)clasts, multinucleated giant cells of the
      monocyte/macrophage lineage, are selectively induced in the GP during
      endochondral ossification and play central roles in the resorption of
      cartilagenous matrices. The aim of this study was to investigate the factors
      determining the GP-specific recruitment of osteo(chondro)clasts. We especially
      focused on the expression pattern of the receptor activator of NF-kappaB ligand
      (RANKL), an essential factor for osteo(chondro)clast differentiation, and on that
      of epigenetic and transcriptional factors affecting RANKL gene expression. Knee
      joints of male BALB/c mice aged 8 weeks were dissected and subjected to
      immunohistochemical analysis using anti-RANKL, Runx2, Dlx5 and Msx2 antibodies.
      The methylation status of the mouse RANKL gene promoter in both the GP and the AC
      was analyzed by sodium bisulfite mapping using microdissected mouse tissue. The
      expression of BMP-2, -3, -4, -6 and type X collagen mRNA was examined by in situ
      hybridization (ISH). At the boundary between the calcifying cartilage and the
      hypertrophic chondrocytes of the GP, RANKL-expressing chondrocytes overlapped
      those expressing Runx2, Dlx5 and Msx2, near numerous osteo(chondro)clasts.
      Although similar BMP-2 and -4 expression was observed in chondrocytes in both the
      GP and the AC as well as in maturing osteoblasts, a rather restricted BMP-6
      expression pattern was observed in resting and proliferating chondrocytes in the
      GP. On the other hand, sodium bisulfite mapping showed that mostly non-CpG
      methylation was similarly scattered in a non-specific manner in chondrocytes in
      the GP and the AC. Taken together with the fact that putative Runx2 binding
      elements are located in the RANKL promoter, our data suggest that Runx2, an
      essential transcription factor for skeletal development, is also a key regulator
      of RANKL expression in chondrocytes in the GP. Furthermore, a selective and
      sequential expression of a subset of BMP and of transcription factors may define
      the expression pattern of RANKL through Runx2.

PMID- 16283361
TI  - The number of satellite cells in slow and fast fibres from human vastus lateralis
      muscle.
AB  - The aim of this investigation was to study the distribution of satellite cells in
      slow (type I fibres) and fast (type II fibres) fibres from human vastus lateralis
      muscle. This muscle is characterised by a mixed fibre type composition and is
      considered as the site of choice for biopsies in research work and for clinical
      diagnosis. Biopsy samples were obtained from five healthy young volunteers and a
      total of 1,747 type I fibres and 1,760 type II fibres were assessed. Satellite
      cells and fibre type composition were studied on serial muscle cross-sections
      stained with specific monoclonal antibodies. From a total of 218 satellite cells,
      116 satellite cells were found in contact with type I fibres (53.6+/-8% of the
      satellite cells associated to type I fibres) and 102 satellite cells in contact
      with type II fibres (46.4+/-8% of the satellite cells associated to type II
      fibres). There was no significant difference (P=0.4) between the percentages of
      satellite cells in contact with type I and with type II fibres. Additionally,
      there was no relationship between the mean number of satellite cells per fibre
      and the mean cross-sectional area of muscle fibres. In conclusion, our results
      show that there is no fibre type-specific distribution of satellite cells in a
      human skeletal muscle with mixed fibre type composition.

PMID- 16283362
TI  - Effects of short- and long-term unemployment on physical work capacity and on
      serum cortisol.
AB  - AIM: To investigate whether a decrease in physical working capacity occurs during
      the first year of unemployment and if this is accompanied by a deterioration in
      mental health. METHODS: In a longitudinal study, 71 unemployed individuals were
      investigated for 1, 6 months and 1 year after becoming unemployed. An additional
      102 individuals who have been unemployed for more than 1 year were included in
      the cross-sectional part of the study. Possible decrease of physical working
      capacity was tested by bicycle ergometry. Psycho-emotional stress was tested by
      serum cortisol concentrations and by the Giessen symptom questionnaire. RESULTS:
      In short-term unemployed (STU) individuals, a significant decrease (P=0.001) of
      physical working capacity (16.3%) and a significant increase (P=0.004) of
      cortisol levels (17.6 microg/dl) was found. The Giessen symptom questionnaire
      score showed an increased emotional disturbance (P=0.035) during unemployment.
      The comparison of long-term unemployed and STU revealed a significant decrease
      (P=0.012) in physical working capacity (18.2%), a significant increase in
      cortisol levels (P=0.001) and a significant worsening of the Giessen symptom
      questionnaire score (P=0.001). CONCLUSION: Unemployment has a negative effect on
      physical working capacity and mental health, depending on the duration of
      unemployment. Factors that facilitate or impede physical and mental health during
      unemployment should be identified in future studies.

PMID- 16283363
TI  - Exposure to particles and nitrogen dioxide among taxi, bus and lorry drivers.
AB  - AIM: The aims of this study have been to investigate the occurrence of systematic
      differences in the personal exposure to motor exhaust between different groups of
      taxi, bus and lorry drivers, and to study if these are influenced by the choice
      of exposure indicator. METHODS: We used one indicator of the gaseous phase,
      nitrogen dioxide (NO(2)), and one of the particle phase (measured by DataRAM), of
      the exhausts. A total of 121 drivers were included in the study: 39 taxi drivers,
      42 bus drivers and 40 lorry drivers. Personal measurements were performed during
      one working day. Nitrogen dioxide was measured with passive diffusive samplers
      and particles with Data-RAM, a logging instrument using nephelometric monitoring.
      The instrument measures particles between 0.1 and 10 microm in size. RESULTS: The
      average exposure to NO(2) for lorry drivers was 68 microg/m(3); for bus drivers
      60 microg/m(3) and for taxi drivers 48 microg/m(3). For particles the exposure
      was 57 microg/m(3) for lorry drivers, 44 microg/m(3) for bus drivers and 26
      microg/m(3) for taxi drivers. The result remained unchanged when exposures were
      adjusted for variation in urban background levels of NO(2) and particulate matter
      with an aerodynamic diameter <10 microm (PM(10)). CONCLUSION: Lorry drivers
      experienced the highest exposure and taxi drivers the lowest with bus drivers in
      an intermediate position, regardless of whether NO(2) or particles were used as
      exposure indicator. The levels of both NO(2) and particles were higher for bus
      drivers in the city than for them driving in the suburbs. Using diesel or petrol
      as a fuel for taxis had no influence on the exposure for the drivers, indicating
      that the taxi drivers' exposure mainly depends on exhaust from surrounding
      traffic.

PMID- 16283364
TI  - Mineralogical and exposure determinants of pulmonary fibrosis among Quebec
      chrysotile miners and millers.
AB  - OBJECTIVES: Lung fibre content was determined for 86 former chrysotile miners and
      millers in two Quebec mining regions: Thetford mines (TM) and the Asbestos region
      (AR). METHODS: Fibres were assessed using transmission electron microscopy (TEM)
      and energy dispersive X-ray spectrometry (EDS). Asbestos body (AB) concentrations
      were assessed by microscopy of tissue digests. Corresponding histological lung
      tissue sections were quantitatively graded for the severity of interstitial
      fibrosis on a 12-point scale. Fibrosis score and its associations with (1) fibre
      concentrations and fibre dimensions within three fibre length intervals (less
      than 5 microm, 5-10 microm, and over 10 microm), and (2) several exposure
      variables were evaluated using correlation coefficients and regression
      techniques. RESULTS: Concentration of short (<5 microm) tremolite fibres was the
      best predictor of fibrosis grade in both mining groups (r=0.44, P<0.01 and
      r=0.39, P<0.01 for TM and AR, respectively). Chrysotile fibre concentration
      showed a lower correlation with the fibrosis grade for subjects from TM only.
      Long (>10 microm) amosite fibre concentration showed a linear relationship with
      the fibrosis score in miners and millers from AR. Exposure variables, including
      smoking, had no predictive value for fibrosis grade. Within fibre length
      categories, fibre dimension was not related to the fibrosis score. CONCLUSION:
      Lung fibre concentration as measured by TEM/EDS, especially that of short (<5
      microm) tremolite fibres, is a better predictor of fibrosis grade in these two
      groups of chrysotile miners than either the concentration of ABs or the duration
      of exposure. Due to the limitation of our counting method, almost all fibres
      longer than 10 microm observed in this study were shorter than 14 microm. Thus,
      if length plays a role in fibrogenesis, it may be related to fibres of greater
      length than those covered in this study.

PMID- 16283366
TI  - Job strain and sick leave among Japanese employees: a longitudinal study.
AB  - OBJECTIVES: The present study is an investigation of the association between job
      stress, determined on the basis of a demand-control model or worksite social
      support at the baseline, and absence due to illness among employed Japanese males
      and females. METHODS: We analyzed 448 male and 81 female subjects who had taken
      no sick leave in the year preceding the baseline (1997) and observed them all
      until 1999. A self-administered questionnaire was the source information
      collected. It consisted of questions on socio-demographic variables, occupations,
      health-related behavior, a Japanese version of the Job Content Questionnaire, and
      the number of absences in the year preceding both the baseline and follow-up.
      Logistic regression analyses were used to determine how the characteristics of a
      job at the baseline affected sickness absence of 5 days or longer per year;
      controls were established for the gender, age, level of education completed,
      occupation, number of cigarettes smoked daily, and the amount of alcohol consumed
      weekly. RESULTS: Compared to the lowest tertile of the ratio of demand to control
      (job strain), the highest tertile was significantly associated with an increased
      risk of sickness absence of 5 days or longer per year (odds ratio 3.02; 95%CI
      1.00-9.16) at follow-up. The dose-response relationship was supported (p for
      trend <0.05). However, individual variables of job demand, job control, and
      worksite social support were not significantly associated with the risk of
      absence from illness. CONCLUSIONS: The study provided prospective evidence that
      job strain leads to an increased risk of sick leave among Japanese employees.

PMID- 16283365
TI  - Local effects in the respiratory tract: relevance of subjectively measured
      irritation for setting occupational exposure limits.
AB  - OBJECTIVES: Chemosensory effects of stimulation by a chemical can either be
      irritating (trigeminal stimulation) or odorous (olfactory stimulation) or both.
      For odorous irritants, a clear-cut distinction between odour and irritation is
      difficult to make. The differences in the lowest concentration found to be
      irritating to the respiratory tract in humans when compared to experimental
      animals has brought much debate in the process of setting occupational exposure
      limits (OELs) for such chemicals. In this paper it will be discussed as to how
      far subjectively measured sensory irritation threshold levels can be used to
      establish OELs. METHODS: Data on respiratory irritation of four odorous irritants
      were retrieved from public literature and discussed, viz. acetone, formaldehyde,
      furfural and sulphur dioxide. RESULTS: Objective measures of irritation yielded
      results that differed from subjective evaluations. Important factors modulating
      the reported levels of irritation and health symptoms include the perception of
      odour intensity, exposure history and the individual's bias to report irritation
      on the basis of his/her prejudice or knowledge of the compound. CONCLUSIONS:
      Subjective measures alone are less appropriate for establishing sensory
      irritation thresholds of odorous irritants and are, therefore, less suitable to
      establish OELs without supporting evidence. Objectively measured irritation in
      humans, the Alarie assay (an experimental animal test assessing the concentration
      that results in a 50% reduction of the breathing frequency) and repeated exposure
      studies in animals may be of help to study objective irritation. If subjective
      measurements are used to study sensory irritation, the study design should at
      least include: measurement of both incidence and severity determined at several
      concentrations, an appropriate (0 ppm) control condition, preferably a non
      irritant odorant control exposure, validated questionnaires and correct
      concentration measurements.

PMID- 16283367
TI  - Power output, isometric strength and steadiness in the leg muscles of pre- and
      postmenopausal women; the effects of hormone replacement therapy.
AB  - There are conflicting reports of the effects of hormone replacement therapy (HRT)
      on strength preservation in postmenopausal women, while any effect on power
      output has received little attention. Decreased steadiness of force generation
      has been reported in older muscles and may be related to the hormonal changes
      associated with the menopause, but the effect of HRT has not been investigated.
      We have studied the effect of HRT on strength, power output and isometric force
      steadiness in healthy women. Sixteen young (aged 27.4 +/- 1.4 years, mean +/-
      SEM) and 29 postmenopausal women were studied. Fifteen of the latter were taking
      HRT (68.1 +/- 1.4 years, HRT+) and 14 (70.5 +/- 1.5 years, HRT-) had never done
      so. During isometric quadriceps contractions the force steadiness (coefficient of
      variation of force) was measured at 10, 25, 50 and 100% maximum voluntary
      contraction (MVC). The average power generated by an explosive leg extension was
      recorded. The HRT- group generated less power (110.2 +/- 7.2 W) than both the
      HRT+ (136.5 +/- 10.9 W, P = 0.027) and young (136.2 +/- 5.8 W, P = 0.027)
      subjects. Power output was similar in the HRT+ and younger subjects. The HRT-
      subjects were weaker than the younger ones (241.3 +/- 14.0 N vs. 297.6 +/- 13 N,
      P = 0.006). The strength of the HRT+ group (255.5 +/- 14 N) was not significantly
      different to the other two groups. There was no difference in steadiness between
      the three groups at any of the force levels. HRT appears to maintain power output
      to a greater extent than isometric strength in postmenopausal women. There was no
      evidence for an effect of either age or HRT on isometric steadiness in the
      quadriceps.

PMID- 16283368
TI  - Relationship between the increase of effectiveness indexes and the increase of
      muscular efficiency with cycling power.
AB  - We determined the index of effectiveness (IE), as defined by the ratio of the
      tangential (effective force) to the total force applied on the pedals, using a
      new method proposed by Mornieux et al. (J Biomech, 2005), while simultaneously
      measuring the muscular efficiency during sub-maximal cycling tests of different
      intensities. This allowed us to verify whether part of the changes in muscular
      efficiency could be explained by a better orientation of the force applied on the
      pedals. Ten subjects were asked to perform an incremental test to exhaustion,
      starting at 100 W and with 30 W increments every 5 min, at 80 rpm. Gross (GE) and
      net (NE) efficiencies were calculated from the oxygen uptake and W(Ext)
      measurements. From the three-dimensional force's measurements, it was possible to
      measure the total force (F(Tot)), including the effective (F(Tang)) and
      ineffective force (F (Rad + Lat)). IE has been determined as the ratio between
      F(Tang) and F(Tot), applied on the pedals for three different time intervals,
      i.e., during the full revolution (IE(360 degrees)), the downstroke phase (IE(180
      degrees Desc)) and the upstroke phase (IE(180 degrees Asc)). IE(360 degrees) and
      IE(180 degrees Asc) were significantly correlated with GE (r = 0.79 and 0.66,
      respectively) and NE (r = 0.66 and 0.99, respectively). In contrast, IE(180
      degrees Desc) was not correlated to GE or to NE. From a mechanical point of view,
      during the upstroke, the subject was able to reduce the non-propulsive forces
      applied by an active muscle contraction, contrary to the downstroke phase. As a
      consequence, the term 'passive phase', which is currently used to characterize
      the upstroke phase, seems to be obsolete. The IE(180 degrees Asc) could also
      explain small variations of GE and NE for a recreational group.

PMID- 16283369
TI  - Adaptation of left ventricular morphology to long-term training in sprint- and
      endurance-trained elite runners.
AB  - Long-term studies on left ventricular (LV) adaptation have not been reported. The
      echocardiograms of 41 top-class runners (8 males and 6 females sprint-trained, 15
      males and 12 females endurance-trained) were recorded at the beginning and after
      1, 2, and 3 years of training. A one-way ANOVA and a linear regression analysis
      were conducted to determine changes and association between performance and LV
      values. Training resulted in an increase in performance and LV internal diameter
      at end-diastole (LVIDd) and decreases in end-diastolic interventricular septal
      wall thickness, and posterior wall thickness (PWTd). There were no significant
      differences in LV mass and LV ejection fraction (LVEF, %). The changes in PWTd
      were linked to enlargement of the LV. In athletes with unusual LV dilatation (>60
      mm), LVIDd was related to performance and LVEF was >50%. Maximal wall thickness
      was <13 mm in all athletes. LV adaptations were independent of sex and type of
      training and related to the initial level of performance. We believe that LV
      enlargement in elite runners is a physiological adaptation and that the LVIDd is
      a predictor of running performance.

PMID- 16283370
TI  - The effects of training intensity on muscle buffer capacity in females.
AB  - We examined changes in muscle buffer capacity (beta m(in vitro)), VO2peak and the
      lactate threshold (LT) after 5 weeks of high-intensity interval training (INT)
      above the LT or moderate-intensity continuous training (CON) just below the LT.
      Prior to and immediately after training, 16 female subjects performed a graded
      exercise test to determine VO2peak and the LT, followed 2 days later by a resting
      muscle biopsy from the vastus lateralis muscle to determine beta m(in vitro).
      Following baseline testing, the subjects were randomly placed into the INT (n=8)
      or CON training group (n=8). Subjects then performed 5 weeks of cycle training (3
      days per week), performing either high-intensity INT (6-10x2 min at 120-140% LT
      with 1 min rest) or moderate-intensity CON (80-95% LT) training. Total training
      volume was matched between the two groups. After the training period, both groups
      had significant improvements in VO2peak (12-14%; P<0.05) and the LT (7-10%;
      P<0.05), with no significant differences between groups. The INT group, however,
      had significantly greater improvements in beta m(in vitro) (25%; 123+/-5-153+/-7
      micromol H+ x g muscle dm(-1) x pH(-1); P<0.05) than the CON group (2%; 130+/-12
      133+/-7 micromol H+ x g muscle dm(-1) x pH(-1), P>0.05). Our results show that
      when matched for training volume, high-intensity interval training above the LT
      results in similar improvements in VO2peak and the LT, but greater improvements
      in beta m(in vitro) than moderate-intensity continuous training below the LT.
      This suggests that training intensity is an important determinant of changes to
      beta m(in vitro).

PMID- 16283371
TI  - Testosterone and human performance: influence of the color red.
AB  - This study examined the testosterone responses of men to an exercise bout
      simulating a competitive sporting effort in order to determine if the wearing of
      red-colored apparel influenced the hormonal response. Male subjects (n = 10) were
      placed into sets of matched-pairs and performed VO(2max) cycle ergometry exercise
      test to exhaustion to simulate the competitive effort. Each member of a pairing
      was randomly assigned to one of two treatment groups-the wearing of red-colored
      clothing, or the wearing of black-colored clothing. Blood samples were collected
      before exercise (REST), an immediate postexercise sample was collected at
      exhaustion (EXH), and a final sample was taken at 15 min into recovery (REC) from
      exercise. Blood was biochemically analyzed for total testosterone. In response to
      the exercise, performance characteristics (i.e., VO(2max) and maximal workload)
      of treatment groups did not differ significantly. A significant increase (P <
      0.01) in the testosterone was observed in both treatment groups postexercise at
      EXH and at REC as compared to REST. However, no differences were observed between
      treatment groups in the before or postexercise hormonal concentrations. These
      findings suggest that the wearing of red-colored apparel had no affects on the
      testosterone responses to an exercise bout simulating a competition.

PMID- 16283372
TI  - Acute changes in muscle activation and leg extension performance after different
      running exercises in elite long distance runners.
AB  - This study investigated acute changes in muscle activation and muscular power
      performance after three different running exercises in elite long-distance
      runners. Twenty-two nationally and internationally ranked long-distance runners
      performed first an incremental treadmill running test until exhaustion (MR) and
      then 40 min continuous (TR) and intermittent (2 min run/2 min rest) (IR) running
      exercises at an intensity of 80 and 100% of the velocity associated with
      VO(2max), respectively. Muscle activation and muscular power performance tests
      (counter-movement jumps, CMJ, and a set of ten maximal half squats from the
      static starting position with an extra load of 35% of the subjects, one
      repetition maximum) were performed before and immediately after the runs. The
      average mechanical power (P) of the half squats was calculated and the root mean
      square electromyogram (EMGrms) from the vastus lateralis, vastus medialis,
      gastrocnemius and biceps femoris muscles was recorded simultaneously during the
      half squat performances. The results showed an acute exercise-induced increase in
      P (ANOVA time effect, P = 0.000) together with a reduction in EMGrms of the knee
      extensor muscles (ANOVA time effect, P = 0.000). However, mechanical P expressed
      as a relative change within the set decreased after MR. In TR the improvement in
      P correlated positively with the maximal running performance of the runners (P <
      0.05), while in IR it correlated negatively (P < 0.05). Jumping performance was
      significantly enhanced after each run (P < 0.001, for all) and the improvement
      correlated negatively with the maximal sprinting speed and maximal jumping height
      of the runners (P < 0.01, for all). It is concluded that in elite long distance
      runners an intensive prolonged running exercise reduces the surface EMG of the
      knee extensor muscles, and may lead to a different coordination strategy in leg
      extension exercises performed into the vertical direction. After continuous type
      of running the power improvement correlates positively with maximal endurance
      running capacity, whereas after intermittent type of running it correlates
      negatively.

PMID- 16283374
TI  - Stability and motor adaptation in human arm movements.
AB  - In control, stability captures the reproducibility of motions and the robustness
      to environmental and internal perturbations. This paper examines how stability
      can be evaluated in human movements, and possible mechanisms by which humans
      ensure stability. First, a measure of stability is introduced, which is simple to
      apply to human movements and corresponds to Lyapunov exponents. Its application
      to real data shows that it is able to distinguish effectively between stable and
      unstable dynamics. A computational model is then used to investigate stability in
      human arm movements, which takes into account motor output variability and
      computes the force to perform a task according to an inverse dynamics model.
      Simulation results suggest that even a large time delay does not affect movement
      stability as long as the reflex feedback is small relative to muscle elasticity.
      Simulations are also used to demonstrate that existing learning schemes, using a
      monotonic antisymmetric update law, cannot compensate for unstable dynamics. An
      impedance compensation algorithm is introduced to learn unstable dynamics, which
      produces similar adaptation responses to those found in experiments.

PMID- 16283375
TI  - A stochastic population approach to the problem of stable recruitment hierarchies
      in spiking neural networks.
AB  - Synchrony-driven recruitment learning addresses the question of how arbitrary
      concepts, represented by synchronously active ensembles, may be acquired within a
      randomly connected static graph of neuron-like elements. Recruitment learning in
      hierarchies is an inherently unstable process. This paper presents conditions on
      parameters for a feedforward network to ensure stable recruitment hierarchies.
      The parameter analysis is conducted by using a stochastic population approach to
      model a spiking neural network. The resulting network converges to activate a
      desired number of units at each stage of the hierarchy. The original recruitment
      method is modified first by increasing feedforward connection density for
      ensuring sufficient activation, then by incorporating temporally distributed
      feedforward delays for separating inputs temporally, and finally by limiting
      excess activation via lateral inhibition. The task of activating a desired number
      of units from a population is performed similarly to a temporal k-winners-take
      all network.

PMID- 16283376
TI  - The ARABIDOPSIS SKP1-LIKE1 (ASK1) protein acts predominately from leptotene to
      pachytene and represses homologous recombination in male meiosis.
AB  - Normal progression of genetic recombination requires timely degradation of many
      proteins, but little is known about the proteolytic mechanism. The ARABIDOPSIS
      SKP1-LIKE1 (ASK1) protein is a component of the Skp1-Cullin-F-box-protein (SCF)
      ubiquitin ligases that target a variety of proteins for degradation via the 26S
      proteasome pathway. Previous studies indicate that the early defects of the
      mutant ask1-1 occur in a prophase-I period overlapping with the period of
      homologous recombination. We provide evidence in this report that ASK1 is
      predominately expressed from leptotene to pachytene, and negatively regulates
      recombination. First, the ASK1 transcript was found not to co-exist with that of
      its closest homolog ASK2 only during prophase I of male meiosis, suggesting that
      ASK1 is functionally non-redundant only in prophase I. Second, the peak level of
      an ASK1-green fluorescence protein (GFP) fusion protein expressed by an ASK1
      promoter region occurred only from leptotene to pachytene. The ASK1-GFP in a
      dominant negative fashion resulted in abnormal tetrads resembling those of the
      ask1-1 mutant, supporting that the expression timing of the ASK1-GFP in male
      meiocytes reflects the expression timing of the endogenous ASK1. Lastly, using a
      marker for recombination events, a significant increase in recombination
      frequency was detected in plants heterozygous for ask1-1. These results indicate
      that ASK1 normally plays a repressive role in male recombination in Arabidopsis.

PMID- 16283377
TI  - Arabidopsis phosphoenolpyruvate carboxylase genes encode immunologically
      unrelated polypeptides and are differentially expressed in response to drought
      and salt stress.
AB  - The phosphoenolpyruvate carboxylase (PEPC) gene family of Arabidopsis is composed
      of four genes. Based on sequence analysis it was deduced that Atppc1, Atppc2 and
      Atppc3 genes encode plant-type PEPCs, whereas Atppc4 encodes a PEPC without
      phosphorylation motif, but no data at the protein level have been reported. Here,
      we describe the analysis of the four Arabidopsis PEPC polypeptides, which were
      expressed in Escherichia coli. Immunological characterization with anti plant
      type PEPC and an anti-AtPPC4 antibody, raised in this work, showed that the
      bacterial-type PEPC is unrelated with plant-type PEPCs. Western-blot analysis of
      different Arabidopsis organs probed with anti plant-type PEPC antibodies detected
      a double band, the one with low molecular weight corresponding to the three plant
      type PEPCs. The high molecular weight subunit is not encoded by any of the
      Arabidopsis PEPC genes. No bands were detected with the anti-AtPPC4 antibody.
      PEPC genes show differential expression in Arabidopsis organs and in response to
      environmental stress. Atppc2 transcripts were found in all Arabidopsis organs
      suggesting that it is a housekeeping gene. In contrast, Atppc3 gene was expressed
      in roots and Atppc1 in roots and flowers, as Atppc4. Highest PEPC activity was
      found in roots, which showed expression of the four PEPC genes. Salt and drought
      exerted a differential induction of PEPC gene expression in roots, Atppc4 showing
      the highest induction in response to both stresses. These results show that PEPC
      is part of the adaptation of the plant to salt and drought and suggest that this
      is the function of the new bacterial-type PEPC.

PMID- 16283378
TI  - Immunohistochemical expression of p63, p53 and MIB-1 in urinary bladder
      carcinoma. A tissue microarray study of 158 cases.
AB  - P63 is a member of the p53 family, which plays a role in the differentiation of
      urothelium and is supposed to play a role in urothelial carcinogenesis. P53 and
      MIB-1 are recognised in many studies as predictive markers of progression, but
      few studies in the literature have examined p63. The aims of our study were to
      explore the expression of p63 in bladder carcinomas and to compare this
      expression to p53 and MIB-1, as well as to stage and grade. Tissue microarrays
      were performed on 158 urothelial carcinomas (56 pTa, 45 pT1 and 57>or=pT2).
      Immunohistochemical studies were performed with p63, p53 and MIB-1 antibodies. In
      our study we observed that p63 immunostaining is present in all cell layers in
      papillary urothelial neoplasm of low malignant potential (PUNLMP), but partially
      lost in non-invasive papillary urothelial carcinoma low grade (NILGC) and in
      pT1/>or=pT2 bladder cancers. P53 and MIB-1 displayed lower expression in
      PUNLMP/NILGC vs non-invasive papillary urothelial carcinoma high grade
      (NIHGC)/pT1, but there was no correlation between the expression of p63, p53 and
      MIB-1. Our study demonstrates that p63 expression distinguishes between
      PUNLMP/NILGC and NIHGC/pT1 (p=4.10(5)). A statistical difference disserving pTa
      and pT1/>or=pT2 with a statistical significance (p<10(-6)) could also be
      observed. P63 should be considered as an additional biomarker that might help
      pathologists to classify their patients.

PMID- 16283379
TI  - Patterns of postural asymmetry in infants: a standardized video-based analysis.
AB  - Cervical rotation deficit (CRD) and trunk convexity (TC) constitute the diagnosis
      of infantile postural asymmetry (IPA), which is often associated with further
      asymmetric features. However, very little data on the entire symptom complex are
      currently available. The aim of this study was to analyse the entire clinical
      spectrum of IPA based on a standardized video documentation. Forty-five infants
      (27 male) with an asymmetry score of > or = 12 points (scale: 4-24) at a median
      post-term age of 10 weeks (range: 6-16) were selected from two previously studies
      using predefined criteria. CRD and TC as reactive movements to an orienting head
      turn in the prone and supine position were assessed from video recordings by
      three independent observers. Plagiocephaly, oblique body position and asymmetric
      foot position were descriptively assessed by consent of the same observers. Hip
      dysplasia data were derived from sonography charts. The assessment of the
      reactive movements showed a "scoliosis" pattern in sox infants, a "torticollis"
      pattern in nine infants, a "mixed prone" pattern in 13 infants and a "mixed"
      pattern in 26 infants. Side agreement in the prone and supine position of TC and
      CRD was seen in 27 infants, with a left-sided convexity and left-sided head
      rotation deficit in two-thirds of the infants. Plagiocephaly was present in 27
      infants, oblique body position in 13 infants, hip dysplasia in 4 infants and
      calcaneus foot in 11 infants. In conclusion, infantile asymmetry pattern analysis
      showed that morphological and functional anomalies are intricately linked and
      that infants with only a single apparent sign of asymmetry have actually a much
      more generalized disturbance.

PMID- 16283380
TI  - Solitary fibrous tumor in the thigh: review of the literature.
AB  - Solitary fibrous tumors (SFT) of extremities, especially the thighs are very
      rare. Despite SFTs are generally benign, well-circumscribed soft tissue tumors
      new cases should be presented and followed up carefully to monitor their
      biological behavior. In general for tumor classification a biopsy is state of the
      art. Histological including immunohistochemical patterns for SFTs are defined.
      MRI and ultrasound are not sufficient for differential diagnosis. Once property
      identified and defined by size and location, resection with intact tumor capsule
      may result in full recovery of the patient. Reviewing the literature there are no
      validated reasons for a wider resection. The current patient was a 41-year-old
      male. Four years after an arthroscopy of the left knee the patient has been
      suffering an ongoing swelling of the lateral thigh. Because MRI scan data
      suggested a synovial sarcoma a biopsy was performed. The tumor was classified as
      a benign SFT. The diagnosis based on histological findings and the presence of
      the positive immunohistochemical markers Vimentin, CD34, and CD99. The complete
      tumor resection with intact capsule was achieved in a final operation. Clinical
      and in MRI after 54-month outcome period there were no local recurrences.

PMID- 16283381
TI  - Effects of doxorubicin-containing chemotherapy and a combination with L-carnitine
      on oxidative metabolism in patients with non-Hodgkin lymphoma.
AB  - PURPOSE: Chemotherapy regimens based on anthracycline (doxorubicin) are well
      established in lymphoma therapy. The purpose of this study was to examine the
      effects of L-carnitine with a view to reducing cytotoxic side-effects. METHODS:
      20 patients were scheduled to receive 3 g L-carnitine before each chemotherapy
      cycle, followed by 1 g L-carnitine/day during the following 21 days, while 20
      patients received a placebo (randomized controlled trial). The plasma lipid
      profile and relative mRNA levels of key enzymes of oxidative metabolism
      (carnitine acyltransferases) were measured at three points of time. In addition
      to the clinical parameters we used the mRNA of white blood cells to evaluate the
      toxic effects on cardiomyocytes. RESULTS: In the present study no cardiotoxicity
      of anthracycline therapy was detected. Carnitine treated patients showed a rise
      in plasma carnitine which led to an increase of relative mRNA levels from CPT1A
      (liver isoform of carnitine palmitoyltransferase) and OCTN2 (carnitine
      transporter). Following chemotherapy, an activation of carnitine acyltransferases
      was associated with a stimulation of OCTN2 in both groups. CONCLUSION:
      Biochemical and molecular analyses indicated a stimulation of oxidative
      metabolism in white blood cells through carnitine uptake.

PMID- 16283382
TI  - Loss of heterozygosity testing using real-time PCR analysis of single nucleotide
      polymorphisms.
AB  - PURPOSE: Colon cancer is a genetic disease, caused by mutations in different
      oncogenes and tumor-suppressor genes. The aim of this study is to evaluate the
      usefulness of real-time PCR SNP analysis as a new technique in the loss of
      heterozygosity (LOH) analysis at the E-cadherin gene locus in sporadic colon
      cancer. METHODS: One-hundred cases of human sporadic colon cancer and
      corresponding normal tissue samples were analyzed using two flanking polymorphic
      markers commonly used in the LOH analysis at the E-cadherin gene locus by
      conventional VNTR-LOH analysis. Two intragenic E-cadherin SNP markers were
      analyzed using real-time PCR SNP analysis. RESULTS: LOH (17.6%) was detected
      using flanking markers, however, no LOH was detected when the intragenic E
      cadherin SNP markers were introduced into our study. Since these markers are
      intragenic they more accurately represent the status of the E-cadherin gene than
      the previously used flanking markers. CONCLUSION: In conclusion, real-time PCR
      SNP analysis was found to be more accurate, faster, simpler, and a more high
      throughput method than the conventional VNTR-LOH analysis.

PMID- 16283383
TI  - Hsp90 inhibitors cause G2/M arrest associated with the reduction of Cdc25C and
      Cdc2 in lung cancer cell lines.
AB  - PURPOSE: Hsp90, a molecular chaperone, is involved in folding, assembly,
      maturation, and stabilization of the client proteins which regulate survival of
      cancer cells, and thus Hsp90 inhibitors may be potential molecular targeting
      agents for cancer treatment. We investigated whether Hsp90 inhibitors have
      therapeutic value in lung cancer. METHODS: First, expression levels of Hsp90 in
      lung cancer cells were examined by western blotting and immunohistochemical
      analyses. Next, the effect of Hsp90 inhibitors, geldanamycin and 17
      allylaminogeldanamycin (17-AAG), on lung cancer cell growth was examined.
      RESULTS: Remarkable high expression of Hsp90 protein in lung cancer cell lines
      and a more intense signal for Hsp90 by immunohistochemistry in males, patients
      with smoking index over 600, and squamous cell carcinoma were observed. Both
      Hsp90 inhibitors dose dependently inhibited the growth of lung cancer cell lines
      and induced G2/M arrest concomitant with decreased protein levels of Cdc25C and
      Cdc2. Moreover, combination of an Hsp90 inhibitor and irradiation had an additive
      effect on cell growth inhibition and reduction of Cdc25C and Cdc2 protein levels.
      CONCLUSION: Hsp90 inhibitor is thus a therapeutic tool for lung cancer based on
      its target proteins, which are involved in tumor progression and
      antiproliferative activity in lung cancer cells.

PMID- 16283384
TI  - Segmental distribution of genes harboring a CpG island-like region on rice
      chromosomes.
AB  - In plant genomes, there exist discrete regions rich in CpG dinucleotides, namely
      CpG clusters. In rice, most of these CpG clusters are associated with genes. Rice
      genes are grouped into one of the five classes according to the position of an
      associated CpG cluster. Among them, class 1 genes, which harbor a CpG cluster at
      the 5'-terminus, share similarities with human genes having CpG islands. In the
      present study, by analyzing plant genome sequence data, primarily from rice, we
      investigated the chromosomal distribution of genes of each class, mainly class 1
      genes. Class 1 genes were not uniformly distributed across the rice genome, but
      were clustered into discrete chromosomal segments. EST-based analysis of the
      distribution of expressed genes indicates that this segmental distribution of
      class 1 genes caused a preferential distribution of expressed genes within class
      1 gene-rich segments. We then compared the methylation status of genes of each
      class to examine the possibility that differential DNA methylation, if any, is
      relevant to the observed differential expression level of genes inside and
      outside the class 1 segments. The difference in the methylation level between
      these genes was revealed to be fairly small, which does not support the above
      mentioned possibility.

PMID- 16283385
TI  - Physical mapping and microsynteny of Brassica rapa ssp. pekinensis genome
      corresponding to a 222 kbp gene-rich region of Arabidopsis chromosome 4 and
      partially duplicated on chromosome 5.
AB  - We constructed a bacterial artificial chromosome (BAC) library, designated as
      KBrH, from high molecular weight genomic DNA of Brassica rapa ssp. pekinensis
      (Chinese cabbage). This library, which was constructed using HindIII-cleaved
      genomic DNA, consists of 56,592 clones with average insert size of 115 kbp. Using
      a partially duplicated DNA sequence of Arabidopsis, represented by 19 and 9
      predicted genes on chromosome 4 and 5, respectively, and BAC clones from the KBrH
      library, we studied conservation and microsynteny corresponding to the
      Arabidopsis regions in B. rapa ssp. pekinensis. The BAC contigs assembled
      according to the Arabidopsis homoeologues revealed triplication and
      rearrangements in the Chinese cabbage. In general, collinearity of genes in the
      paralogous segments was maintained, but gene contents were highly variable with
      interstitial losses. We also used representative BAC clones, from the assembled
      contigs, as probes and hybridized them on mitotic (metaphase) and/or meiotic
      (leptotene/pachytene/metaphase I) chromosomes of Chinese cabbage using bicolor
      fluorescence in situ hybridization. The hybridization pattern physically
      identified the paralogous segments of the Arabidopsis homoeologues on B. rapa
      ssp. pekinensis chromosomes. The homoeologous segments corresponding to
      chromosome 4 of Arabidopsis were located on chromosomes 2, 8 and 7, whereas those
      of chromosome 5 were present on chromosomes 6, 1 and 4 of B. rapa ssp.
      pekinensis.

PMID- 16283386
TI  - Isolation and analysis of sequences showing sex-specific cytosine methylation in
      the mealybug Planococcus lilacinus.
AB  - Genomic libraries of Planococcus lilacinus, a mealybug in which paternal
      chromosomes are facultatively heterochromatic and inactive in sons but not in
      daughters, were probed with subtraction probes in order to estimate the number of
      sequences displaying sex-specific cytosine methylation in CpG dinucleotides.
      Sequences showing male-specific methylation were found to occur approximately 2.5
      times more often than those showing female-specific methylation. In order to
      directly isolate sequences showing sex-specific CpG methylation, we employed
      methylation-specific arbitrarily primed (MS-AP) polymerase chain reaction (PCR)
      and identified 72 sex-specific products, of which 51 were from males and 21 from
      females. Amplification of bisulfite-modified DNA and subsequent Southern
      hybridization showed that in 33 out of these 72 sex-specific products, there was
      differential methylation of homologous sequences; i.e., both methylated and
      unmethylated copies of the same sequence occurred in one sex whereas only
      unmethylated copies were present in the opposite sex. Sequencing of bisulfite
      modified DNA showed an interspersion of CpG and non-CpG methylation among the sex
      specifically methylated sequences. Sequences showing male-specific CpG
      methylation are organized as transcriptionally silent chromatin in males but not
      in females, whereas those showing female-specific CpG methylation are organized
      as transcriptionally silent chromatin in females but not in males. The sequences
      identified in this study that show differential methylation in males, but are
      unmethylated in females, may prove useful in the study of imprinting in the
      mealybug system.

PMID- 16283387
TI  - A clinical and molecular study of 26 females with Xp deletions with special
      emphasis on inherited deletions.
AB  - We have undertaken a clinical study of 26 females with deletions of Xp including
      five mother-daughter pairs. Cytogenetic and molecular analyses have mapped the
      breakpoints of the deletions. We determined the parental origin of each
      abnormality and studied the X-inactivation patterns. We describe the clinical
      features and compare them with the amount of Xp material lost. We discuss the
      putative loci for features of Turner syndrome and describe how our series
      contributes further to their delineation. We conclude that (1) fertility can be
      retained even with the loss of two-thirds of Xp, thus, if there are genes on Xp
      for ovarian development, they must be at Xp11-Xp11.2; (2) in our sample of
      patients there is no evidence to support the existence of a single lymphogenic
      gene on Xp; (3) there is no evidence for a second stature locus in proximal Xp;
      (4) there is no evidence to support the existence of a single gene for naevi; (5)
      we suggest that the interval in Xp21.1-Xp11.4 between DXS997 and DXS1368 may
      contain a gene conferring a predisposition to hypothyroidism.

PMID- 16283388
TI  - Population stratification confounds genetic association studies among Latinos.
AB  - In the United States, asthma prevalence and mortality are the highest among
      Puerto Ricans and the lowest among Mexicans. Case-control association studies are
      a powerful strategy for identifying genes of modest effect in complex diseases.
      However, studies of complex disorders in admixed populations such as Latinos may
      be confounded by population stratification. We used ancestry informative markers
      (AIMs) to identify and correct for population stratification among Mexican and
      Puerto Rican subjects participating in case-control studies of asthma. Three
      hundred and sixty-two subjects with asthma (Mexican: 181, Puerto Rican: 181) and
      359 ethnically matched controls (Mexican: 181, Puerto Rican: 178) were genotyped
      for 44 AIMs. We observed a greater than expected degree of association between
      pairs of AIMs on different chromosomes in Mexicans (P < 0.00001) and Puerto
      Ricans (P < 0.00002) providing evidence for population substructure and/or recent
      admixture. To assess the effect of population stratification on association
      studies of asthma, we measured differences in genetic background of cases and
      controls by comparing allele frequencies of the 44 AIMs. Among Puerto Ricans but
      not in Mexicans, we observed a significant overall difference in allele
      frequencies between cases and controls (P = 0.0002); of 44 AIMs tested, 8 (18%)
      were significantly associated with asthma. However, after adjustment for
      individual ancestry, only two of these markers remained significantly associated
      with the disease. Our findings suggest that empirical assessment of the effects
      of stratification is critical to appropriately interpret the results of case
      control studies in admixed populations.

PMID- 16283389
TI  - Linkage methods in human genetics before the computer.

PMID- 16283390
TI  - Presence and localization of antithrombin and its regulation after acute
      lipopolysaccharide exposure in amphioxus, with implications for the origin of
      vertebrate liver.
AB  - Antithrombin (AT), which is mainly synthesized in the liver, is an acute-phase
      plasma protein in mammalian species. Here, we demonstrated that sheep anti-human
      AT antibody cross-reacted with the humoral fluids in amphioxus Branchiostoma
      belcheri tsingtauense as well as human serum. The concentration of AT in the
      humoral fluids in amphioxus decreased slightly at first and then increased after
      the acute challenge with lipopolysaccharide, while the level of total proteins
      remained unchanged. These suggest the presence of the same acute-phase response
      pattern in amphioxus, as observed in some mammalian species.
      Immunohistochemically, AT was localized in the hepatic diverticulum. It is clear
      that the hepatic diverticulum in amphioxus is homologous to the vertebrate liver
      with respect to AT synthesis. This lends support to the hypothesis originally
      suggested by Muller that the vertebrate liver evolved from the hepatic
      diverticulum of an amphioxus-like ancestor during early chordate evolution.

PMID- 16283391
TI  - Apoptotic process of porcine intestinal M cells.
AB  - Membranous (M) cells of the follicle-associated epithelium (FAE) are believed to
      sample antigens from the gut lumen. However, the origin, differentiation
      mechanism, and cell death of M cells are still a matter of controversy.
      Therefore, we investigated the process of M cell differentiation and determined
      their fate in the intestine of three-way crossbred female pigs. We used anti
      cytokeratin 18 and anti-PCNA antibodies to distinguish M cells and proliferative
      cells and performed immunohistochemistry, enzyme histochemistry, and scanning
      electron microscopy on fresh ileal Peyer's patches. Cell migration and apoptotic
      cells were detected by BrdU labeling and the TUNEL method, respectively. The
      turnover of the FAE was similar to that of the villi. M cells were mostly
      observed from the FAE crypt to the FAE periphery, but not in the FAE apex. As
      proliferative M cells (cytokeratin 18(+)/PCNA(+) cells) have previously been
      detected in the FAE crypt, porcine M cells may be directly derived from
      intestinal epithelial stem cells and committed as a distinct cell lineage in the
      crypts. M cells from the FAE periphery were unstained or only weakly stained for
      alkaline phosphatase, whereas cytokeratin 18(+)/alkaline phosphatase(+) cells
      lying near to the FAE apex showed a columnar shape similar to that of adjacent
      enterocytes. These data suggest that the committed M cells differentiate to
      mature M cells by contact with lymphocytes at the FAE periphery, and that they
      trans-differentiate to enterocytes and are finally excluded near the FAE apex.

PMID- 16283392
TI  - PTEN is involved in the signal transduction pathway of contact inhibition in
      endometrial cells.
AB  - PTEN is involved in the regulation of normal cellular functions in addition to
      its well-known role as a tumor suppressor. In the present study, we have shown
      that stable transfection of the PTEN gene into PTEN-mutated endometrial carcinoma
      cells leads to contact inhibition accompanied by a decreased level of
      phosphorylated-Akt (p-Akt) expression, an increase in p27(Kip1), and a decrease
      in beta-catenin. PTEN-induced cells with contact inhibition exhibit G0-G1 cell
      cycle arrest, and the Ki-67 labeling index is reduced. These changes are canceled
      by transfection of a double-stranded short-interfering RNA against the PTEN gene.
      Normal endometrial stromal cells increase their PTEN expression when reaching
      confluence; this is followed by changes in the expression of Akt-related proteins
      in the same way as in tumor cells. These results indicate that PTEN, p-Akt, p27,
      and beta-catenin are involved in the signal transduction of contact inhibition
      and suggest that PTEN may, in part, control the proliferation of endometrial
      carcinoma cells through the induction of contact inhibition.

PMID- 16283393
TI  - Exogenous manganous ion at millimolar levels rescues all known dioxygen-sensitive
      phenotypes of yeast lacking CuZnSOD.
AB  - Yeasts lacking copper-zinc superoxide dismutase (sod1Delta) exhibit a broad range
      of phenotypes, many of which can be rescued by growth in the presence of high
      levels of ionic manganese. We undertook a comprehensive survey of the effects of
      manganese on wild-type and sod1Delta yeasts and found that 5 mM Mn2+ rescued all
      known growth-related phenotypes, such as slow growth in air, temperature
      sensitivity, specific amino acid auxotrophies, no growth in high oxygen, poor
      growth in nonfermentable carbon sources, and decreased stationary-phase survival.
      Iron-related phenotypes-elevated electron paramagnetic resonance detectable
      ("free") iron, decreased aconitase activity, and fragmenting vacuoles-as well as
      zinc sensitivity were also rescued. The activity of manganese superoxide
      dismutase remained constant or was reduced when the yeasts were grown in the
      presence of MnCl2, indicating that induction of this alternative superoxide
      dismutase is not the explanation. In contrast to MnCl2 treatment, addition of two
      manganese-containing superoxide dismutase mimetic compounds to the growth medium
      did not provide any rescue of sod1Delta yeast growth but rather had an sod1Delta
      selective inhibitory effect at micromolar concentrations. Mechanisms by which
      ionic manganese can effect this rescue, while the mimetic compounds do not, are
      discussed.

PMID- 16283394
TI  - New insights into the mechanism of nickel insertion into carbon monoxide
      dehydrogenase: analysis of Rhodospirillum rubrum carbon monoxide dehydrogenase
      variants with substituted ligands to the [Fe3S4] portion of the active-site C
      cluster.
AB  - Carbon monoxide dehydrogenase (CODH) from Rhodospirillum rubrum catalyzes the
      oxidation of CO to CO2. A unique [NiFe4S4] cluster, known as the C-cluster,
      constitutes the active site of the enzyme. When grown in Ni-deficient medium R.
      rubrum accumulates a Ni-deficient apo form of CODH that is readily activated by
      Ni. It has been previously shown that activation of apo-CODH by Ni is a two-step
      process involving the rapid formation of an inactive apo-CODH*Ni complex prior to
      conversion to the active holo-CODH. We have generated CODH variants with
      substitutions in cysteine residues involved in the coordination of the [Fe3S4]
      portion of the C-cluster. Analysis of the variants suggests that the cysteine
      residues at positions 338, 451, and 481 are important for CO oxidation activity
      catalyzed by CODH but not for Ni binding to the C-cluster. C451S CODH is the only
      new variant that retains residual CO oxidation activity. Comparison of the
      kinetics and pH dependence of Ni activation of the apo forms of wild-type, C451S,
      and C531A CODH allowed us to develop a model for Ni insertion into the C-cluster
      of CODH in which Ni reversibly binds to the C-cluster and subsequently
      coordinates Cys531 in the rate-determining step.

PMID- 16283395
TI  - Functional characterisation of an engineered multidomain human P450 2E1 by
      molecular Lego.
AB  - The human cytochrome P450s constitute an important family of monooxygenase
      enzymes that carry out essential roles in the metabolism of endogenous compounds
      and foreign chemicals. We present here results of a fusion between a human P450
      enzyme and a bacterial reductase that for the first time is shown does not
      require the addition of lipids or detergents to achieve wild-type-like
      activities. The fusion enzyme, P450 2E1-BMR, contains the N-terminally modified
      residues 22-493 of the human P450 2E1 fused at the C-terminus to residues 473
      1049 of the P450 BM3 reductase (BMR). The P450 2E1-BMR enzyme is active, self
      sufficient and presents the typical marker activities of the native human P450
      2E1: the hydroxylation of p-nitrophenol (KM=1.84+/-0.09 mM and kcat of 2.98+/
      0.04 nmol of p-nitrocatechol formed per minute per nanomole of P450) and
      chlorzoxazone (KM=0.65+/-0.08 mM and kcat of 0.95+/-0.10 nmol of 6
      hydroxychlorzoxazone formed per minute per nanomole of P450). A 3D model of human
      P450 2E1 was generated to rationalise the functional data and to allow an
      analysis of the surface potentials. The distribution of charges on the model of
      P450 2E1 compared with that of the FMN domain of BMR provides the ground for the
      understanding of the interaction between the fused domains. The results point the
      way to successfully engineer a variety of catalytically self-sufficient human
      P450 enzymes for drug metabolism studies in solution.

PMID- 16283396
TI  - [Saving life and permitting death. Decision conflicts in intensive medicine].
AB  - Intensive care has achieved major breakthroughs in handling gravely ill patients.
      However, this has, at least in part, been overshadowed by problems relating to
      ethical values as well as general psychological conflicts among patients and
      hospital staff. When dealing with such problems, distinct criteria are required
      which address the patient's dignity and will to survive. A four-step scheme is
      suggested, ranging from maximum therapy, via maintenance therapy without
      adjustments to increased demand and therapy reduction, to cessation of therapy.
      In the case of therapy reduction, balanced support is maintained ensuring that
      dehydration is avoided, the respiratory tract is kept clear, pain killers are
      used to good effect, personal attention is provided, and care is provided to a
      high standard. A questionnaire tailored to the practical need of how to arrive at
      an ethically weighted and accepted decision is presented. When searching for a
      solution involving ethic issues, it is particularly important to involve all
      individuals concerned in a dialogue until a consensus is reached.

PMID- 16283397
TI  - A portable surface plasmon resonance sensor system for real-time monitoring of
      small to large analytes.
AB  - Many environmental applications exist for biosensors capable of providing real
      time analyses. One pressing current need is monitoring for agents of chemical-
      and bio-terrorism. These applications require systems that can rapidly detect
      small organics including nerve agents, toxic proteins, viruses, spores and whole
      microbes. A second area of application is monitoring for environmental
      pollutants. Processing of grab samples through chemical laboratories requires
      significant time delays in the analyses, preventing the rapid mapping and cleanup
      of chemical spills. The current state of development of miniaturized, integrated
      surface plasmon resonance (SPR) sensor elements has allowed for the development
      of inexpensive, portable biosensor systems capable of the simultaneous analysis
      of multiple analytes. Most of the detection protocols make use of antibodies
      immobilized on the sensor surface. The Spreeta 2000 SPR biosensor elements
      manufactured by Texas Instruments provide three channels for each sensor element
      in the system. A temperature-controlled two-element system that monitors for six
      analytes is currently in use, and development of an eight element sensor system
      capable of monitoring up to 24 different analytes will be completed in the near
      future. Protein toxins can be directly detected and quantified in the low
      picomolar range. Elimination of false positives and increased sensitivity is
      provided by secondary antibodies with specificity for different target epitopes,
      and by sensor element redundancy. Inclusion of more than a single amplification
      step can push the sensitivity of toxic protein detection to femtomolar levels.
      The same types of direct detection and amplification protocols are used to
      monitor for viruses and whole bacteria or spores. Special protocols are required
      for the detection of small molecules. Either a competition type assay where the
      presence of analyte inhibits the binding of antibodies to surface-immobilized
      analyte, or a displacement assay, where antibodies bound to analyte on the sensor
      surface are displaced by free analyte, can be used. The small molecule detection
      assays vary in sensitivity from the low micromolar range to the high picomolar.

PMID- 16283398
TI  - Task-dependent effects of social attention on saccadic reaction times.
AB  - Previous research has shown that saccadic reaction times (SRTs) are shorter when
      a stimulus is flashed on the same side as the observed gaze direction of another
      individual. The gaze imitation hypothesis contends that observed gaze evokes the
      preparation of a saccade toward the same direction. Previous studies of this
      phenomenon have employed pro-saccade tasks in which the instructed saccade is
      directed toward the stimulus. In agreement with previous findings, we found that
      SRTs on pro-saccade trials were shorter when the stimulus appeared in the same
      direction as observed gaze. Here we also included anti-saccade trials in which
      subjects were required to look-away from a stimulus and toward its mirror
      position in the opposite visual field. The gaze imitation hypothesis predicts
      that subjects will have shorter SRTs on anti-saccade trials in which the stimulus
      appears opposite the observed gaze direction because they will have prepared
      already a saccade in that direction. However, contrary to the prediction of the
      gaze imitation hypothesis, we found that subjects had shorter SRTs on anti
      saccade trials when the stimulus appeared in the same direction as observed gaze.
      Moreover, subjects also made more pro-saccade errors on anti-saccade trials in
      which the stimulus was presented opposite the observed gaze direction. The
      results of our study indicate that subjects prepared a saccade in the same
      direction as observed gaze on pro-saccade trials but opposite the observed gaze
      direction on anti-saccade trials. These findings suggest that the effect of
      social gaze cues on SRTs is task dependent.

PMID- 16283399
TI  - Early phase of spatial mismatch negativity is localized to a posterior "where"
      auditory pathway.
AB  - The auditory mismatch negativity (MMN) is an event-related potential that
      reflects early processing of changes in acoustic stimulus features. Although the
      MMN has been well characterized by previous work, the number, roles, and
      anatomical locations of its cortical generators remain unresolved. Here, we
      report that the MMN elicited by occasional deviations in sound location is
      comprised of two temporally and anatomically distinct phases: an early phase with
      a generator posterior to auditory cortex and contralateral to the deviant
      stimulus, and a later phase with generators that are more frontal and bilaterally
      symmetric. The posterior location of the early-phase generator suggests the
      engagement of neurons within a putative "where" pathway for processing spatial
      auditory information.

PMID- 16283400
TI  - Postural responses and spatial orientation to neck proprioceptive and vestibular
      inputs during locomotion in young and older adults.
AB  - Both vestibular and neck proprioceptive inputs contribute towards maintaining a
      walking trajectory. We investigated how aging alters neck proprioceptive and
      vestibular interaction for preserving equilibrium and spatial orientation during
      locomotion. Young and healthy elderly were exposed to two sensory manipulations
      as they walked, eyes closed, to a target located straight ahead: (1) right side
      dorsal neck muscle vibration (Vib), and (2) Vib + transmastoidal galvanic
      vestibular stimulation (Vib + GVS). The maximum path deviation, average frontal
      centre of mass velocity and average trunk roll were evaluated. Trunk yaw rotation
      was computed at every metre of the path. We observed that directional responses
      to neck muscle stimulation were very sensitive to the reference frame generated
      by vestibular information. The attenuation of path deviation in older adults can
      be attributed to a reduced sensitivity of the neck proprioceptive system rather
      than the vestibular system.

PMID- 16283401
TI  - Training BIG to move faster: the application of the speed-amplitude relation as a
      rehabilitation strategy for people with Parkinson's disease.
AB  - We have used the phenomenon that speed increases with movement amplitude as a
      rehabilitation strategy. We tested the hypothesis that the generalized training
      of amplitude in the limb motor system may reduce bradykinesia and hypokinesia in
      the upper and lower limbs in subjects with Parkinson's disease (PD) across
      disease severity (Stage I, n=6; Stage II, n=7; Stage III, n=5). While studies
      have separately examined the relationship of amplitude to speed in reaching and
      gait, the same study has not reported the relationship for both limb systems.
      Moreover, the rehabilitation intervention, Training BIG, is unique in that it
      applies well-established treatment concepts from a proven treatment for the
      speech motor system in PD [Lee Silverman Voice Treatment (LSVT)] to the limb
      motor system. Subjects (n=18) participated in intense practice (1-h sessions/4x
      week/4 weeks) of large amplitude movements involving the whole body (i.e., head,
      arm, trunk, and leg) while focusing on the sensory awareness of "movement
      bigness." Testing procedures were designed to demonstrate the transfer of
      generalized amplitude practice to speed improvements during functional
      "untrained" tasks in "uncued" conditions with blinded testers. After therapy, the
      subjects significantly increased their speed of reaching and gait for the
      preferred speed condition. This effect was greater when the severity of the
      disease was less. The results support further application and efficacy studies of
      Training BIG. Amplitude-based behavioral intervention in people with PD appears
      to be a simple target that may be applied in different contexts for multiple
      tasks and results in improved speed-amplitude scaling relations across the upper
      and lower limbs.

PMID- 16283402
TI  - Synaptic influences of pontine nuclei on cochlear nucleus cells.
AB  - Using the in vitro isolated whole brain preparation of the guinea pig, we tested
      the synaptic effects induced by the stimulation of pontine nuclei (PN) in
      intracellularly recorded and stained principal cells of the cochlear nucleus
      (CN). Twenty percent of the recorded cells in all CN subdivisions responded to
      stimulation of either ipsilateral or contralateral PN, and 12% of the cells
      exhibited convergence of inputs from both sides. The responses were recorded only
      in stellate cells of the ventral CN and in the pyramidal cells of the dorsal CN,
      whereas no responses were observed in bushy, octopus, and giant cells. PN
      stimulation produced excitatory and inhibitory postsynaptic potentials as well as
      mixed responses. The heterogeneous nature and the wide latency range (3.2-18 ms)
      of observed responses suggest significant variability in the underlying synaptic
      mechanisms and the implicated pathways. We propose that PN projections to the CN,
      terminating mainly in the granule cell domain (GCD), together with other non
      auditory and auditory inputs contribute to multimodal convergence in the GCD
      leading ultimately to modulatory actions on the output activity of CN principal
      cells.

PMID- 16283403
TI  - Sensory input from the moving hand influences saccadic eye movements during
      reading.
AB  - Reading involves saccadic eye movements. Measured reading time and the number of
      mistakes made while reading reflect the speed and accuracy of the saccades in
      target localization, if all other factors influencing these parameters are kept
      constant. The observed phenomenon that reading a book is easier when it is held
      in an individual's hand than when it is not, especially when movement of the
      reading text occurs while travelling in a vehicle, raises the question of the
      role of sensory input from the moving arms in guiding saccades in the direction
      in which the text is moved. To address this question, 12 healthy subjects (6
      males and 6 females), aged 19-21 years took part in this study where reading time
      and the number of mistakes made while reading a non-moving standardized printed
      text was noted. Similar printed texts were read by the subjects while
      mechanically moving them at different fixed speeds in the horizontal plane, with
      and without the subject's arms moving with the text. At each speed, the reading
      time recorded when the subject's arms moved with the text was significantly
      lesser than when they did not (P<0.05). The number of mistakes made were
      significantly more when not moving the arms than when moving them with the text,
      at higher speed of text movement (P<0.05). The results indicate that sensory
      input from the passively moving arms guided saccades in the direction of movement
      of the text during reading.

PMID- 16283404
TI  - Diazepam-induced changes of optokinetic nystagmus fast phase.
AB  - Since specific benzodiazepine (Bz) binding sites have been found in the vision
      and oculomotor control areas of the central nervous system (CNS), the fast phases
      of optokinetic nystagmus (OKN) should be affected by Bz administration. In this
      study, we examine the effects of Bzs on OKN fast phases under closed- and open
      loop experimental conditions. Six normal subjects participated in the
      experiments. The eye movements were measured by the magnetic field, search coil
      technique, 90 min after diazepam or placebo administration. The study was
      performed in a randomized, double-blind fashion. After diazepam, the mean
      amplitude (MAmp) and mean peak velocity (MVel) of OKN fast phases decreased
      significantly under both experimental conditions. The percentage decreases in
      MAmp and MVel under the open-loop condition were significantly larger than those
      under the closed-loop condition. The results indicate that the fast phases of OKN
      could sensitively reflect the pharmacodynamic effects of Bzs on the CNS.

PMID- 16283405
TI  - Extensive genomic and functional polymorphism of the complement control proteins.
AB  - Using combinations of genomic markers, we describe more than 20 distinct
      ancestral haplotypes (AH) of complement control proteins (CCPs), located within
      the regulators of complement activation (RCA) alpha block at 1q32. This extensive
      polymorphism, including functional sites, is important because CCPs are involved
      in the regulation of complement activation whilst also serving as self and viral
      receptors. To identify haplotypes, we used the genomic matching technique (GMT)
      based on the pragmatic observation that extreme nucleotide polymorphism is
      packaged with duplicated sequences as polymorphic frozen blocks (PFB). At each
      PFB, there are many alternative sequences (haplotypes) which are inherited
      faithfully from very remote ancestors. We have compared frequencies of RCA
      haplotypes and report differences in recurrent spontaneous abortion (RSA) and
      psoriasis vulgaris (PV).

PMID- 16283406
TI  - High efficiency plant production of North American ginseng via somatic
      embryogenesis from cotyledon explants.
AB  - An efficient in vitro protocol for plant production of North American ginseng has
      been established. The pretreatment of cotyledon explants with 1.0 M sucrose at 4
      degrees C resulted in an improvement of embryo quality and, combined with a
      higher sucrose content (7%) in induction medium, improved the embryogenesis
      frequency from 40% to 75% and the number of embryos per explant from 10 to 21.
      The frequency of secondary embryogenesis from somatic embryo-derived tissues
      cultured on MS medium with 1.0 mg l(-1) 2, 4-D and 1.0 mg l(-1) NAA is up to 90%.
      Somatic embryos can further develop to maturity on SH medium supplemented with 1%
      activated charcoal and half of them can germinate. About 85% of the germinated
      embryos will convert into plants with well-developed taproot systems on 1/2 SH
      medium with 0.5% activated charcoal. The growth chamber and field establishment
      rates were 95.6 and 93.7%, respectively. The plants transplanted to growth
      chambers and field plots appear normal.

PMID- 16283407
TI  - Gastric carcinoma diagnosed at the third trimester: a case report.
AB  - Gastric carcinoma associated with pregnancy appears to be an extremely rare
      entity. It is usually diagnosed at advanced stages of the disease and presents a
      grave prognosis. Since the fatal outcome shows a rapid course within months of
      diagnosis, prompt gastroduodenal endoscopic examination following early clinical
      suspicion is mandatory. A case of 29 year-old pregnant woman with 31 weeks of
      gestation is herein presented. The women was diagnosed as gastric adenocarcinoma
      while being investigated for intractable nausea, vomiting, and a concomitant
      epigastric mass. She underwent radical gastric resection and received six cycles
      of adjuvant chemotherapy following vaginal delivery of a healthy 1950 g fetus.
      The patient was dead 20 weeks after the surgery due to pulmonary and hepatic
      metastasis.

PMID- 16283408
TI  - Twin gestation in older women: antepartum, intrapartum complications, and
      perinatal outcomes.
AB  - OBJECTIVE: The aim of this study is to present pregnancy and perinatal outcomes
      of twin gestations in older women and compare them with that for younger women.
      STUDY DESIGN: We conducted a retrospective cohort study of twin pregnancies in
      our department between 1988 and 2003. The women were classified into two groups
      by maternal age: women of age 35 years and older (study group) and women less
      than 35 years (control group). Population characteristics, complications during
      pregnancy and delivery, and neonatal outcomes were assessed. The Student's t
      test, chi2 test, Fisher exact test, and binary logistic regression analysis were
      used to examine the relationship between maternal age and the different
      variables. RESULTS: A total of 238 twin pregnancies were enrolled (study group,
      57 women; control group, 181 women). Spontaneous conceptions were significantly
      higher in the control group (P < 0.001), while conceptions after in vitro
      fertilization (IVF) were significantly higher in study group (P < 0.001). Mean
      figures of gestational age at delivery and birth weight for the older group did
      not differ significantly from the younger group. Although the antepartum and
      intrapartum complications were more common in the study group, they were not
      statistically significant compared to the control group. This was also true for
      the perinatal outcomes. Only the very low birth weight (VLBW < 1,500 g) rate was
      significantly higher in the study group. The number of perinatal deaths was
      similar on comparison by maternal age. CONCLUSIONS: Based on our study, advanced
      maternal age at twin gestation does not seem to affect significantly pregnancy
      complications and perinatal outcomes. VLBW was the only unfavorable perinatal
      outcome related to advanced maternal age.

PMID- 16283409
TI  - Response-specific sources of dual-task interference in human pre-motor cortex.
AB  - It is difficult to perform two tasks at the same time. Such performance
      limitations are exemplified by the psychological refractory period (PRP): when
      participants make distinct motor responses to two stimuli presented in rapid
      succession, the response to the second stimulus is increasingly slowed as the
      time interval between the two stimuli is decreased. This impairment is thought to
      reflect a central limitation in selecting the appropriate response to each
      stimulus, but not in perceptually encoding the stimuli. In the present study, it
      was sought to determine which brain regions are specifically involved in response
      selection under dual-task conditions by contrasting fMRI brain activity measured
      from a response selection manipulation that increased dual-task costs, with brain
      activity measured from an equally demanding manipulation that affected perceptual
      visibility. While a number of parieto-frontal areas involved in response
      selection were activated by both dual-task manipulations, the dorsal pre-motor
      cortex, and to a lesser extent the inferior frontal cortex, were specifically
      engaged by the response selection manipulation. These results suggest that the
      pre-motor cortex is an important neural locus of response selection limitation
      under dual-task situations.

PMID- 16283410
TI  - Entamoeba histolytica sequences and their relationship with experimental liver
      abscesses in hamsters.
AB  - The purpose of the present paper was to analyse the association between sequences
      of Entamoeba histolytica and their relationship with the development of hepatic
      abscesses in hamsters, using a complementary DNA library for E. histolytica. From
      the sequences obtained, we designed oligonucleotides for amplification by PCR.
      Trophozoites were isolated from faeces of 11 patients in whom cysts from E.
      histolytica were identified, and these trophozoites were then subjected to
      monoaxenic culture. Then 1 x 10(5) trophozoites were inoculated into hamster
      liver, with three hamsters used for every culture. Sequences were obtained for
      ubiquitin, lectin surface precursor, replication factor MCM3 and surface antigen.
      The associations between sequences and hepatic abscesses were: 11/11 for
      ubiquitin, 9/11 for lectin precursor, 4/11 for replication factor and 1/11 for
      surface antigen. These results suggest that ubiquitin could be an important
      protein involved in the mechanism of E. histolytica invasion.

PMID- 16283411
TI  - Putrescine analogue cytotoxicity against Trypanosoma cruzi.
AB  - Trypanosoma cruzi is the etiological agent of American trypanosomiasis. Most of
      the available data on trypanosomatid parasites were obtained from African
      trypanosomes. Parasitic protozoa polyamine metabolism and transport pathways
      comprise valuable targets for chemotherapy. T. cruzi cannot synthesize
      putrescine, but its uptake from the extracellular milieu can promote parasite
      survival. Nevertheless, little is known about the cell biology of this diamine in
      T. cruzi. Here we notice that the putrescine analogue 1,4-diamino-2-butanone
      (DAB) inhibited T. cruzi epimastigotes' in vitro proliferation and produced
      remarkable mitochondrial destruction and cell architecture disorganization, as
      assessed by transmission electron microscopy. Mitochondrial damage was confirmed
      by MTT reduction. We decided to analyze the oxidative stress undergone by DAB
      treated parasites. Thiobarbituric-acid-reactive substances were measured to
      assess lipid peroxidation. Analogue effects were dose-dependent; 5 mM DAB only
      slightly enhanced peroxidation, whereas 10 mM DAB significantly (P < 0.05)
      diminished it. These data indicate that putrescine uptake by this diamine
      auxotrophic parasite may be important for epimastigote axenic growth and cellular
      organization.

PMID- 16283412
TI  - Modelling the effect of a booster vaccination on disease epidemiology.
AB  - Despite the effectiveness of vaccines in dramatically decreasing the number of
      new infectious cases and severity of illnesses, imperfect vaccines may not
      completely prevent infection. This is because the immunity afforded by these
      vaccines is not complete and may wane with time, leading to resurgence and
      epidemic outbreaks notwithstanding high levels of primary vaccination. To prevent
      an endemic spread of disease, and achieve eradication, several countries have
      introduced booster vaccination programs. The question of whether this strategy
      could eventually provide the conditions for global eradication is addressed here
      by developing a seasonally-forced mathematical model. The analysis of the model
      provides the threshold condition for disease control in terms of four major
      parameters: coverage of the primary vaccine; efficacy of the vaccine; waning
      rate; and the rate of booster administration. The results show that if the
      vaccine provides only temporary immunity, then the infection typically cannot be
      eradicated by a single vaccination episode. Furthermore, having a booster program
      does not necessarily guarantee the control of a disease, though the level of
      epidemicity may be reduced. In addition, these findings strongly suggest that the
      high coverage of primary vaccination remains crucial to the success of a booster
      strategy. Simulations using estimated parameters for measles illustrate model
      predictions.

PMID- 16283413
TI  - A structured-population model of Proteus mirabilis swarm-colony development.
AB  - In this paper we present continuous age- and space-structured models and
      numerical computations of Proteus mirabilis swarm-colony development. We base the
      mathematical representation of the cell-cycle dynamics of Proteus mirabilis on
      those developed by Esipov and Shapiro, which are the best understood aspects of
      the system, and we make minimum assumptions about less-understood mechanisms,
      such as precise forms of the spatial diffusion. The models in this paper have
      explicit age-structure and, when solved numerically, display both the temporal
      and spatial regularity seen in experiments, whereas the Esipov and Shapiro model,
      when solved accurately, shows only the temporal regularity. The composite
      hyperbolic-parabolic partial differential equations used to model Proteus
      mirabilis swarm-colony development are relevant to other biological systems where
      the spatial dynamics depend on local physiological structure. We use
      computational methods designed for such systems, with known convergence
      properties, to obtain the numerical results presented in this paper.

PMID- 16283414
TI  - On the (dis) advantages of cannibalism.
AB  - Cannibalism is an interaction between individuals that can produce counter-
      intuitive effects at the population level. A striking effect is that a population
      may persist under food conditions such that the non-cannibalistic variant is
      doomed to go extinct. This so-called life boat mechanism has received
      considerable attention. Implicitly, such studies sometimes suggest, that the life
      boat mechanism procures an evolutionary advantage to the cannibalistic trait.
      Here we compare, in the context of a size structured population model, the
      conditions under which the life boat mechanism works, with those that guarantee,
      that a cannibalistic mutant can invade successfully under the steady
      environmental conditions as set by a non-cannibalistic resident. We find
      qualitative agreement and quantitative difference. In particular, we find that a
      prerequisite for the life boat mechanism is, that cannibalistic mutants are
      successful invaders. Roughly speaking, our results show that cannibalism brings
      advantages to both the individuals and the population when adult food is
      limiting.

PMID- 16283416
TI  - Nasal Wegener's and skin sarcoid--a rare combination of two granulomatous
      diseases.
AB  - Wegener's granulomatosis (WG) and sarcoidosis are two distinct granulomatous
      diseases characterized by multisystem involvement. We report a patient who
      initially presented with symptoms of limited WG predominantly affecting the nose,
      followed by a facial rash, which was histologically proven to be due to
      sarcoidosis. The sequential development of these two diseases in one patient is
      very rare, and to our knowledge, only one such case has been reported in the last
      50 years (Am J Kidney Dis 28:893-898, 1996).

PMID- 16283417
TI  - Successful treatment of a patient with primary Sjogren's syndrome with Rituximab.
AB  - We report the course of a 55-year-old woman, the first patient with primary
      Sjogren's syndrome and distal renal tubular acidosis but without lymphoma to be
      treated with B-cell depletion using Rituximab. Rapidly after B-cell depletion,
      remarkable improvement in xerostomia occurred, while serological findings and
      tubular acidosis have been unchanged. In labial salivary gland biopsy, lymphocyte
      infiltration and particularly CD20-positive cells decreased strikingly. Aquaporin
      1 (AQP-1) expression in myoepithelial cells was very low before treatment and
      increased noticeably. Apical AQP-5 in acinus cells likewise increased following
      Rituximab. In contrast, basolateral NKCC1 was expressed at unchanged intensity
      before and following Rituximab. The improvement has been sustained and still is
      most gratifying 10 months after treatment. B-cell depletion may be effective
      treatment in Sjogren's syndrome. Likewise, it may now be possible to separate the
      immunologic phenomena in Sjogren's syndrome from the consequences of prolonged
      hyposalivation when studying the pathophysiology of xerostomia.

PMID- 16283418
TI  - Sequential evaluation of clinical and laboratory changes amongst children
      suffering from lupus nephritis during intermittent intravenous cyclophosphamide
      therapy.
AB  - We prospectively evaluated the efficacy and safety of a 24-month course of
      intermittent intravenous cyclophosphamide (IC) therapy for children suffering
      from lupus nephritis soon after the diagnosis of systemic lupus erythematosus
      (SLE) was made. Eight children with severe lupus nephritis were treated with IC
      monthly for 6 months and then every 3 months, totaling 24 months. The repeated
      measurements of sequential serological parameters of lupus nephritis, monitored
      over the course of the study, were analyzed statistically. The urine creatinine
      clearance rate (Ccr), the 24-h urine protein excretion, and the serum creatinine
      level significantly improved (p<0.05) after 6, 9 and 12 months of treatment,
      respectively. The serum C3, C4, albumin, and triglyceride level, the hemoglobin
      level, and the erythrocyte sedimentation rate significantly improved (p<0.05) 1
      month after treatment. The IC appeared to elicit a significant effect (p<0.05)
      upon the mean leukocyte and neutrophil counts but had no effect (p>0.05) on the
      platelet count. The lymphocyte count decreased (p<0.05) during the first six
      monthly IC, whereas the lymphocyte count returned to the baseline level during
      the quarterly IC events. From a total of 96 IC doses given to those SLE patients,
      severe myelotoxicity occurred in one patient when lymphocyte count declined to 98
      mm(-3); however, no sign of clinical infection was observed. The daily steroid
      dosage can be tapered rapidly, and the SLE-associated hyperlipidemia resolved
      parallel to the resolution of the acute lupus nephritis. We concluded that the
      efficacy of a 24-month IC course for a child suffering from lupus nephritis is
      significant.

PMID- 16283419
TI  - Acute respiratory failure revealing adult-onset Still's disease: diagnostic value
      of low glycosylated ferritin level.
AB  - The authors report three cases of adult-onset Still's disease with severe
      hypoxemic pulmonary involvement, mimicking severe pulmonary sepsis. Clinicians
      must be aware of this rare form of such disease. Low (<20%) glycosylated ferritin
      level in the presence of unexplained prolonged fever with leukocytosis can help
      in the diagnosis.

PMID- 16283420
TI  - Anti-cyclic citrullinated peptide antibody in rheumatic diseases other than
      rheumatoid arthritis.

PMID- 16283421
TI  - Obstruction after Burch colposuspension: a return to retropubic urethrolysis.
AB  - We compare our postoperative outcomes of a vaginal vs abdominal urethrolysis
      after an obstructed Burch colposuspension. We performed a retrospective review of
      all women who had undergone a Burch urethrolysis from 1997 through 2003. Data
      collected included pelvic examination, cystoscopic and urodynamic findings,
      surgical morbidity, and pre- and postoperative urogynecologic symptomatology.
      Sixteen women underwent Burch urethrolysis. Preoperative symptoms were
      obstructive in 6, overactive in 2, and both (obstructive/overactive) in 8. All
      had an acute retropubic angulation of the urethral axis as well as a retropexed
      urethra that prohibited sagittal rotation of a rigid cystoscope. Seventy-eight
      percent of the women with urodynamic information met urodynamic criteria for
      urethral obstruction. Average follow-up was 7 months, and of those undergoing a
      vaginal urethrolysis, three out of seven (43%) had resolution of their
      obstructive or overactive symptoms postoperatively. In contrast, seven out of
      nine women (78%) who underwent a retropubic urethrolysis had relief of their
      obstructive or overactive bladder symptoms. In our cohort study, an abdominal
      retropubic urethrolysis was more successful in relieving urethral obstruction
      than a vaginal urethrolysis.

PMID- 16283422
TI  - Solifenacin: as effective in mixed urinary incontinence as in urge urinary
      incontinence.
AB  - Patients with mixed urinary incontinence (MUI) are frequently treated with
      antimuscarinic therapy, despite little data being previously published for this
      patient group. We present a subgroup analysis of patients with overactive bladder
      syndrome, assessing the efficacy of once-daily solifenacin succinate in patients
      with MUI (n = 1041) or urge urinary incontinence (UUI; n = 1648) only. A greater
      proportion of patients receiving solifenacin achieved resolution of incontinence
      in both the MUI and UUI groups (MUI: 5 mg = 43%, 10 mg = 49%; UUI: 5 mg = 55%, 10
      mg = 54%) compared with patients receiving placebo (MUI 33%, UUI 35%). Baseline
      to endpoint improvements in all other symptoms were statistically significant vs
      placebo for both solifenacin doses in both cohorts. The incidence of adverse
      events was comparable between the MUI and UUI cohorts. This analysis shows that
      once-daily solifenacin was as effective and well tolerated in patients with MUI
      as in patients with UUI.

PMID- 16283423
TI  - The behavioral ecology of sympatric African apes: implications for understanding
      fossil hominoid ecology.
AB  - The behavioral ecology of the great apes is key evidence used in the
      reconstruction of the behavior of extinct ape and hominid taxa. Chimpanzees and
      gorillas have been studied in detail in the wild, and some studies of their
      behavioral ecology in sympatry have also been been carried out. Although the two
      ape species have divergent behavior and ecology in important respects, recent
      studies have shown that the interspecific differences are not as stark as
      previously thought and subsequently urge new consideration of how they share
      forest resources when sympatric. These new data require re-examination of
      assumptions about key aspects of chimpanzee-gorilla ecological divergence, such
      as diet, ranging and nesting patterns, and the mating system. Diet is a key
      component of the species' adaptive complexes that facilitates avoidance of direct
      competition from the other. While the nutritional basis for chimpanzee food
      choice remains unclear and no doubt varies from site to site, this species is a
      ripe fruit specialist and ranges farther during periods of ripe fruit scarcity.
      Gorillas in the same habitat also feed on ripe fruit when widely available, but
      fall back onto fibrous plant foods during lean periods. The inclusion of animal
      protein in the diet of the chimpanzees and its absence in that of the gorillas
      also distinguish the species ecologically. It may also offer clues to aspects of
      ecological divergence among early members of the hominid phylogeny. The paper
      concludes by suggesting likely characteristics of sympatric associations of
      Pliocene hominids, based on field data from extant sympatric apes.

PMID- 16283424
TI  - Demographic influences on the behavior of chimpanzees.
AB  - Recent research has revealed substantial diversity in the behavior of wild
      chimpanzees. Understanding the sources of this variation has become a central
      focus of investigation. While genetic, ecological, and cultural factors are often
      invoked to explain behavioral variation in chimpanzees, the demographic context
      is sometimes overlooked as a contributing factor. Observations of chimpanzees at
      Ngogo, Kibale National Park, Uganda, reveal that the size and structure of the
      unit group or community can both facilitate and constrain the manifestation of
      behavior. With approximately 150 individuals, the Ngogo community is much larger
      than others that have been studied in the wild. We have taken advantage of the
      unusual demographic structure of this community to document new and intriguing
      patterns of chimpanzee behavior with respect to hunting, territoriality, and male
      social relationships. Chimpanzees at Ngogo hunt often and with a considerable
      degree of success. In addition, male chimpanzees there frequently patrol the
      boundary of their territory and engage in repeated bouts of lethal intergroup
      aggression. By forming two distinct subgroups, male chimpanzees at Ngogo also
      develop social bonds above the level of dyadic pairs. While the sheer number of
      chimpanzees contributes to differences in hunting, patrolling, mating, and
      subgrouping at Ngogo, the demographic situation may also constrain behavioral
      interactions. At Ngogo, male chimpanzees who are closely related genetically
      through the maternal line do not appear to affiliate or cooperate with each
      other. Demographic constraints may be responsible for this finding. In this
      paper, I use these examples to illustrate how the demographic context affects the
      possible range of behavioral options open to individuals and ultimately
      contributes to the explanation of behavioral diversity in chimpanzees.

PMID- 16283425
TI  - Biological behavior of myoepithelial cells in the regeneration of rat atrophied
      sublingual glands following release from duct ligation.
AB  - The present study aimed to clarify how myoepithelial cells behave during
      regeneration of an atrophied sublingual gland by investigating cell proliferation
      and ultrastructure. Atrophy of rat sublingual glands was induced by unilateral
      ligation of the excretory duct near the hilum with metal clips, which were then
      removed after one week of ligation for regeneration. The sublingual glands 0-14
      days after unligation were examined with single immunohistochemistry for actin as
      a marker of myoepithelial cells, double immunohistochemistry for actin and
      proliferating cell nuclear antigen (PCNA) as a marker of proliferating cells, and
      transmission electron microscopy (TEM). The single immunohistochemistry and TEM
      showed that myoepithelial cells surrounded residual ducts in the atrophied glands
      and immature and mature acini in the regenerating glands. Although PCNA-positive
      myoepithelial cells were identified during regeneration, PCNA labeling indices of
      myoepithelial cells were low at all time points except at day 7.
      Ultrastructurally, myoepithelial cells showing bizarre shaped structures in the
      atrophy changed with maturation of differentiating acinar cells and appeared
      normal in the regenerated glands. There was no differentiation of the remaining
      duct cells to myoepithelial cells. These observations suggest that proliferation
      of myoepithelial cells and differentiation to myoepithelial cells do not commonly
      participate in the regeneration of atrophied sublingual glands and that the
      bizarre shaped myoepithelial cells in the atrophied sublingual glands recover the
      original shapes with acinar cell regeneration.

PMID- 16283426
TI  - The apparent absence of lamin B1 and emerin in many tissue nuclei is due to
      epitope masking.
AB  - Immunolocalization studies have concluded that the nuclear membrane protein,
      emerin, is absent from many cell types and that lamin B1 is absent from adult
      heart and skeletal muscle. We now show that epitope masking in the nucleus is
      often responsible for failure to detect emerin and lamins in human, rat and pig
      tissues. Human heart cardiomyocyte nuclei were negative for lamin B1 using a
      commercial mAb, but were positive using two other lamin B1 antibodies, mAb8D1 and
      pAbB1-cbs. Rat hippocampal neuronal nuclei were immunostained by mAb8D1, but not
      pAbB1-cbs, while the commercial antibody stained only a subset. These data
      suggest that different regions of the lamin B1 molecule are masked in different
      tissues. Similarly, pig spleen had fewer emerin-positive nuclei than lung (5% vs.
      32%), although their emerin content was similar by Western blotting. As mAbs
      against six epitopes gave the same result, the whole emerin molecule is either
      masked or redistributed in a subset of cells. Our findings argue that
      immunostaining evidence can be misleading for expression of nuclear envelope
      proteins. Problems with lamin B1 immunostaining can be avoided by using mAb8D1,
      but use of antibodies recognizing different epitopes may reveal cell-specific
      protein interactions in the nucleus.

PMID- 16283427
TI  - Estimation of protein secondary structure content directly from NMR spectra using
      an improved empirical correlation with averaged chemical shift.
AB  - We have recently shown that the averaged chemical shift (ACS) of a nucleus in the
      protein backbone correlates well empirically to its secondary structure content
      (SSC). This allows the estimation of SSC directly from the NMR spectrum without
      the time intensive process of chemical shift assignment. Here, we present an
      empirical correlation that accounts both for contributions to the relevant
      protein and chemical shift databases made subsequent to the original analysis,
      and for missing or inconsistently referenced resonances. Our results affirm that
      this method provides a significant tool for initial structural prediction from
      NMR data prior to complete chemical shift assignment.

PMID- 16283428
TI  - Crystal structures of a phosphotransacetylase from Bacillus subtilis and its
      complex with acetyl phosphate.
AB  - Phosphotransacetylase (Pta) [EC 2.3.1.8] plays a major role in acetate metabolism
      by catalyzing the reversible transfer of the acetyl group between coenzyme A
      (CoA) and orthophosphate: CH(3)COSCoA+HPO(4)(2-)<-->CH(3)COOPO(3)(2-) +CoASH. In
      this study, we report the crystal structures of Pta from Bacillus subtilis at
      2.75 A resolution and its complex with acetyl phosphate, one of its substrates,
      at 2.85 A resolution. In addition, the Pta activity of the enzyme has been
      assayed. The enzyme folds into an alpha/beta architecture with two domains
      separated by a prominent cleft, very similar to two other known Pta structures.
      The enzyme-acetyl phosphate complex structure reveals a few potential substrate
      binding sites. Two of them are located in the middle of the interdomain cleft:
      each one is surrounded by a region of strictly and highly conserved residues.
      High structural similarities are found with 4-hydroxythreonine-4-phosphate
      dehydrogenase (PdxA), and isocitrate and isopropylmalate dehydrogenases, all of
      which utilize NADP+ as their cofactor, which binds in the interdomain cleft.
      Their substrate binding sites are close to the acetyl phosphate binding sites of
      Pta in the cleft as well. These results suggest that the CoA is likely to bind to
      the interdomain cleft of Pta in a similar way as NADP+ binds to the other three
      enzymes.

PMID- 16283429
TI  - Towards miniaturization of a structural genomics pipeline using micro-expression
      and microcoil NMR.
AB  - In structural genomics centers, nuclear magnetic resonance (NMR) screening is in
      increasing use as a tool to identify folded proteins that are promising targets
      for three-dimensional structure determination by X-ray crystallography or NMR
      spectroscopy. The use of 1D 1H NMR spectra or 2D [1H,15N]-correlation
      spectroscopy (COSY) typically requires milligram quantities of unlabeled or
      isotope-labeled protein, respectively. Here, we outline ways towards
      miniaturization of a structural genomics pipeline with NMR screening for folded
      globular proteins, using a high-density micro-fermentation device and a microcoil
      NMR probe. The proteins are micro-expressed in unlabeled or isotope-labeled
      media, purified, and then subjected to 1D 1H NMR and/or 2D [1H,15N]-COSY
      screening. To demonstrate that the miniaturization is functioning effectively, we
      processed nine mouse homologue protein targets and compared the results with
      those from the "macro-scale" Joint Center of Structural Genomics (JCSG) high
      throughput pipeline. The results from the two pipelines were comparable,
      illustrating that the data were not compromised in the miniaturized approach.

PMID- 16283430
TI  - Inhibitory mechanisms of low concentrations of oxidized low-density lipoprotein
      on platelet aggregation.
AB  - The intracellular mechanisms underlying oxidized low-density lipoprotein (oxLDL)
      signaling pathways in platelets are not yet completely understood. Therefore, the
      aim of this study was to further examine the effects of oxLDL in prevention of
      platelet aggregation. In this study, oxLDL concentration-dependently (40-120
      microg/ml) inhibited platelet aggregation in human platelet-rich plasma
      stimulated by agonists. Moreover, oxLDL (40 and 80 microg/ml) markedly decreased
      the fluorescence intensity of platelet membranes tagged with diphenylhexatriene.
      Rapid phosphorylation of a protein of Mr 47,000 (P47), a marker of protein kinase
      C activation, was triggered by PDBu (150 nM). This phosphorylation was markedly
      inhibited by oxLDL (40 and 80 microg/ml) in phosphorus-32-labeled platelets. In
      addition, oxLDL (40 and 80 microg/ml) markedly increased levels of cyclic AMP and
      cyclic AMP-induced vasodilator-stimulated phosphoprotein (VASP) Ser(157)
      phosphorylation. The thrombin-evoked increase in pHi was inhibited in the
      presence of oxLDL (40 and 80 microg/ml). These results indicate that the
      antiplatelet activity of oxLDL may involve the following pathways. (1) oxLDL may
      initially induce conformational changes in platelet membranes, leading to
      inhibition of the activation of protein kinase C, followed by inhibition of P47
      protein phosphorylation, and intracellular Ca(2+) mobilization. (2) oxLDL also
      activated formation of cyclic AMP and cyclic AMP-induced VASP Ser(157)
      phosphorylation, resulting in inhibition of the Na(+)/H(+)exchanger; this leads
      to reduced intracellular Ca(2+) mobilization, and ultimately to inhibition of
      platelet aggregation. This study further provides new insights concerning the
      effects of low concentrations of oxLDL on platelet aggregation.

PMID- 16283431
TI  - Opposite effect of ERK1/2 and JNK on p53-independent p21WAF1/CIP1 activation
      involved in the arsenic trioxide-induced human epidermoid carcinoma A431 cellular
      cytotoxicity.
AB  - While arsenic trioxide (As2O3) is an infamous carcinogen, it is also an effective
      chemotherapeutic agent for acute promyelocytic leukemia and some solid tumors. In
      human epidermoid carcinoma A431 cells, we found that As2O3 induced cell death in
      time- and dose-dependent manners. Similarly, dependent regulation of the
      p21WAF1/CIP1 (p21) promoter, mRNA synthesis, and resultant protein expression was
      also observed. Additionally, transfection of a small interfering RNA of p21 could
      block the As2O3-induced cell growth arrest. The As2O3-induced p21 activation was
      attenuated by inhibitors of EGFR and MEK in a dose-dependent manner. Using a
      reporter assay, we demonstrated the involvement of the EGFR-Ras-Raf-ERK1/2
      pathway in the promoter activation. In contrast, JNK inhibitor enhanced the As2O3
      induced p21 activation, also in a dose-dependent fashion. Over-expression of a
      dominant negative JNK plasmid likewise also enhanced this activation.
      Furthermore, MEK inhibitor attenuated the anti-tumor effect of As2O3. In
      contrast, in combination with JNK inhibitor and As2O3 enhanced cellular
      cytotoxicity. Therefore, we conclude that in A431 cells the ERK1/2 and JNK
      pathways might differentially contribute to As2O3-induced p21 expression and then
      due to cellular cytotoxicity.

PMID- 16283432
TI  - Mesenchymal stem cells are superior to angiogenic growth factor genes for
      improving myocardial performance in the mouse model of acute myocardial
      infarction.
AB  - Both cell therapy and angiogenic growth factor gene therapy have been applied to
      animal studies and clinical trials. Little is known about the direct comparison
      between cell therapy and angiogenic growth factor gene therapy. The goal of this
      study was to compare the effects of human bone marrow-derived mesenchymal stem
      cells (hMSCs) transplantation and injection of angiogenic growth factor genes in
      a model of acute myocardial infarction in mice. The hMSCs were obtained from
      adult human bone marrow and expanded in vitro. The purity and characteristics of
      hMSCs were identified by flow cytometry and immunophenotyping. Immediately after
      ligation of the left anterior descending coronary artery in male severe combined
      immunodeficient (SCID) mice, culture-expanded hMSCs or angiogenic growth factor
      genes were injected intramuscularly at the left anterior free wall. The engrafted
      hMSCs were positive for cardiac marker, desmin. Infarct size was significantly
      smaller in the hMSCs-treated group than in the angiopoietin-1 (Ang-1) or vascular
      endothelial growth factor (VEGF)-treated group at day 28 after infarction. hMSCs
      transplantation was better in decreasing left ventricular end-diastolic dimension
      and increasing fractional shortening than Ang1 or VEGF gene therapy. Capillary
      density was markedly increased after hMSCs transplantation than Ang1 and VEGF
      gene therapy. In conclusion, intramyocardial transplantation of hMSCs improves
      cardiac function after acute myocardial infarction through enhancement of
      angiogenesis and myogenesis in the ischemic myocardium. hMSCs are superior to
      angiogenic growth factor genes for improving myocardial performance in the mouse
      model of acute myocardial infarction. Transplantation of MSCs may become the
      future therapy for acute myocardial infarction for myocardial regeneration.

PMID- 16283433
TI  - Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through its
      anti-oxidative effect and modulation of NF-kappa B activation.
AB  - Infarction in adult rat brain was induced by middle cerebral arterial occlusion
      (MCAO) followed by reperfusion to examine whether taxifolin could reduce cerebral
      ischemic reperfusion (CI/R) injury. Taxifolin administration (0.1 and 1.0
      microg/kg, i.v.) 60 min after MCAO ameliorated infarction (by 42%+/-7% and 62%+/
      6%, respectively), which was accompanied by a dramatic reduction in
      malondialdehyde and nitrotyrosine adduct formation, two markers for oxidative
      tissue damage. Overproduction of reactive oxygen species (ROS) and nitric oxide
      (NO) via oxidative enzymes (e.g., COX-2 and iNOS) was responsible for this
      oxidative damage. Taxifolin inhibited leukocyte infiltration, and COX-2 and iNOS
      expressions in CI/R-injured brain. Taxifolin also prevented Mac-1 and ICAM-1
      expression, two key counter-receptors involved in firm adhesion/transmigration of
      leukocytes to the endothelium, which partially accounted for the limited
      leukocyte infiltration. ROS, generated by leukocytes and microglial cells,
      activated nuclear factor-kappa B (NF-kappaB) that in turn signaled up-regulation
      of inflammatory proteins. NF-kappaB activity in CI/R was enhanced 2.5-fold over
      that of sham group and was inhibited by taxifolin. Production of both ROS and NO
      by leukocytes and microglial cells was significantly antagonized by taxifolin.
      These data suggest that amelioration of CI/R injury by taxifolin may be
      attributed to its anti-oxidative effect, which in turn modulates NF-kappaB
      activation that mediates CI/R injury.

PMID- 16283434
TI  - Differential expression of a V-type ATPase C subunit gene, Atp6v1c2, during
      culture of rat lung type II pneumocytes.
AB  - The lung alveolar epithelium consists of type I and type II pneumocytes. In vivo,
      the type II cell is the progenitor cell from which the type I cell originates.
      When freshly-isolated type II cells are cultured under conventional conditions
      they rapidly lose their phenotypic properties and attain characteristics of type
      I cells. Taking advantage of this transdifferentiation, we sought to identify
      genes that are differentially expressed during culture of rat type II cells.
      Using suppression subtractive hybridization (SSH), a vacuolar-type H+-ATPase (V
      ATPase) C2 subunit gene (Atp6v1c2) was found to be enriched in freshly isolated
      rat type II cells compared to those cultured for 4 days. Northern blotting and
      reverse-transcription polymerase chain reaction (RT-PCR) confirmed the
      differential expression of Atp6v1c2 during in vitro culture of isolated type II
      cells. Expression ofAtp6v1c2 was significantly reduced early during in vitro
      culture: almost 90% reduction was observed after 24 h of incubation as determined
      by real-time PCR. In situ hybridization showed that Atp6v1c2 is expressed in both
      bronchiolar and alveolar lung epithelial cells, an expression pattern similar to
      that of surfactant protein B (SP-B). Multi-tissue Northern blotting revealed a
      unique tissue distribution with Atp6v1c2 expression limited to lung, kidney and
      testis. The presence and expression of Atp6v1c2 gene transcript isoforms,
      resulting from alternative splicing, were also investigated. Elucidation of
      differential expression of Atp6v1c2 in type II cells and further studies of its
      regulation may provide information useful in understanding the molecular
      mechanism underlying phenotypic and functional changes during
      transdifferentiation of alveolar epithelial cells.

PMID- 16283435
TI  - Initial experiences of palliative stereotactic radiosurgery for recurrent brain
      lymphomas.
AB  - In Kyoto University Hospital, stereotactic radiosurgery (SRS) has been performed
      for its rapid palliative effect in patients with recurrent primary central
      nervous system lymphoma (PCNSL), often in combination with salvage chemotherapy.
      In the present study, the treatment outcome and toxicity of SRS for recurrent
      PCNSL was retrospectively evaluated. Between March 1998 and June 2004, 17
      histologically proven recurrent PCNSLs in nine patients were treated with linac
      based stereotactic radiosurgery. All patients had developed intracranial
      recurrences after initial treatment including external beam radiation therapy
      (EBRT). The prescribed dose was 10.0-16.0 (median 12.0) Gy. Seven of nine
      patients received systemic chemotherapy around the time of SRS. The target volume
      was 0.4-24.5 ml (median 3.5 ml). Initial tumor response could be evaluated in 15
      of 17 lesions. Among them, radiological complete response (CR), partial response
      (PR), stable disease (SD) and progressive disease (PD) was observed in 3, 10, 2,
      and 0 lesions, respectively. One-year overall survival rate and relapse-free
      survival rate after first SRS was 58% and 22%, respectively. Improvement of
      symptoms was observed in six patients. The time from SRS to symptomatic relief
      was 1-57 days (median 3 days). No > or = grade 2 acute toxicities related to SRS
      were observed. In conclusion, linac-based SRS with a prescription dose of 10-12
      Gy for recurrent PCNSL is useful for palliation, especially considering the short
      time, rapid tumor response, and low treatment toxicity.

PMID- 16283436
TI  - Intracavitary chemotherapy (Gliadel) for recurrent esthesioneuroblastoma: case
      report and review of the literature.
AB  - Esthesioneuroblastoma is an uncommon malignancy of the nasal vault with a
      treatment regimen consisting of surgical resection followed by radiotherapy for
      primary lesions and addition of chemotherapy for patients with advanced,
      recurrent or metastatic lesions. We report a case of a 39-year-old female with a
      history of esthesioneuroblastoma, previously treated with resection, radiation
      and chemotherapy, presenting with a recurrent disease that was successfully
      treated with re-resection and placement of Gliadel) wafers in the surgical
      resection cavity. The novel option of controlled-release and local delivery of a
      chemotherapeutic agent for treatment of recurrent esthesioneuroblastoma should be
      recognized and considered.

PMID- 16283437
TI  - Loss of 22q chromosome is related to glioma progression and loss of 10q.
AB  - Loss of heterozygosity (LOH) of chromosome 22q has been investigated in 160
      gliomas. LOH at one or more microsatellite increased with increasing grade of the
      tumor (P < 0.01). LOH22q was more frequent in astrocytic tumors (37%) compared to
      mixed or oligodendroglial tumors (21%) (P = 0.02). LOH22q was correlated to 10q
      loss but not to 1p or 9p loss. Taken together, these data suggest that LOH22q is
      an alteration associated with malignant progression of gliomas.

PMID- 16283438
TI  - Cell-specific but p53-independent regulation of vascular endothelial growth
      factor expression by interferons in human glioblastoma cells.
AB  - Vascular endothelial growth factor (VEGF) is a key mediator of tumor
      angiogenesis. Interferons (IFNs) have been widely used in the treatment of
      malignant or recurrent gliomas with only marginal benefit. The association
      between IFNs and VEGF expression remains unclear and should be an intensively
      investigated subject. The present study therefore examined the effects of
      different types of IFNs on VEGF expression in human T98G, A172 and U251
      glioblastoma cells by quantitative RT-PCR and ELISA. Both type I (alpha, beta)
      and type II (gamma) IFNs upregulated VEGF expression in a cell-specific but p53
      independent manner. Actinomycin D experiments demonstrated that IFNs did not
      alter VEGF mRNA stability. In contrast, induction of VEGF mRNA by IFNs was
      blocked by the protein synthesis inhibitor cycloheximide. Interestingly,
      cycloheximide also blocked IFN-induced activation of the p44/p42 mitogen
      activated protein kinase, which was partially required for induction of VEGF by
      IFNs. These findings suggest that VEGF might be an indirect target gene of IFNs,
      and might provide insights into therapeutic applications of IFNs against
      angiogenesis-dependent tumors.

PMID- 16283439
TI  - Metastatic osteosarcoma to the brain in adult patient.

PMID- 16283440
TI  - Paraganglioma of the lumbar spinal canal.

PMID- 16283441
TI  - Primary intradural myxoid chondrosarcoma: a case report and review in the
      literature.
AB  - OBJECTIVE AND IMPORTANCE: Chondrosarcomas are extremely rare cartilaginous
      tumours that typically usually are associated with bone. Therapeutic experience
      with primary spinal mesenchymal chondrosarcomas is also extremely limited. The
      exact origin of rare intradural spinal chondrosarcomas remains obscure. We report
      the first case in the literature of a primary intradural myxoid chondrosarcoma.
      CLINICAL PRESENTATION: This 40-year-old man experienced a 3 month history with
      back pain. The results of his neurological examination were normal. Magnetic
      resonance imaging (MRI)demonstrated at the T12 level intradural tumour. We could
      not identify this lesion as chondrosarcoma in preoperative period. INTERVENTION:
      At surgery, a mass found attached solely to pia mater, with a normal arachnoid
      and dura mater overlying was seen. The mass was excised completely and
      microscopic examination identified a myxomatous chondrosarcoma. The postoperative
      course was unremarkable. But a histological examination revealed primary myxoid
      chondrosarcoma. Experience with primary spinal mesenchymal chondrosarcomas is
      also extremely limited. We especially discussed to the histological examination.
      CONCLUSION: The differential diagnosis considered in the present case included
      meningioma, plasmacytoma, and non-neoplastic intradural spinal cord lesion. We
      emphasize the benefit of surgical resection without radiotherapy and/or
      chemotherapy. This case presents the first case in the literature of an primary
      spinal intradural myxoid chondrosarcoma.

PMID- 16283442
TI  - Intracranial nasal natural killer/T-cell lymphoma: immunopathologically-confirmed
      case and review of literature.
AB  - Advances in immunophenotypic profiling now permit characterization of natural
      killer/T-cell (NK/T-cell) lymphoma as distinct from other extranodal T- and B
      cell Non-Hodgkin's lymphomas. NK/T-cell lymphoma presents most commonly in the
      nasal cavity. Disease progression to the central nervous system (CNS) is a rare
      phenomenon. We present here, to our knowledge, the first immunophenotypically
      confirmed case of direct extension of nasal NK/T-cell lymphoma to the brain. In
      addition, we review the literature with respect to NK/T-cell lymphoma metastasis
      to the CNS. The overall prevalence of NK/T-cell lymphoma CNS metastasis is less
      than 3%. Although rare, CNS invasion portends a poor prognosis, emphasizing the
      importance of early and accurate immunophenotype profiling and the need for
      novel, aggressive therapy.

PMID- 16283443
TI  - Aggressive vestibular schwannomas showing postoperative rapid growth - their
      association with decreased p27 expression.
AB  - Vestibular schwannomas (VSs) are relatively slow growing tumors. However, some
      rapidly regrow or recur after surgical resection. The objective of this study was
      to identify those molecular characteristics predicting rapid recurrence after
      surgical resection. Immunohistochemically determined expressions of several cell
      cycle regulators and apoptosis-associated proteins in 12 cases of aggressive VS
      (AVS) and in 15 control cases of usual VS (UVS) cases were compared. The
      expressions of p53 and Bax (pro-apoptotic protein), Bcl-2 (anti-apoptotic
      protein), Fas, and Fas-L (apoptotic death receptor and ligand), caspase 3
      (apoptotic effector caspase proteins), and p27 and p21 (cyclin-dependent kinase
      inhibitors) were analyzed using tissue array blocks. Loss of p27 expression was
      observed in 8 of 12 AVS cases (67%) and in 3 UVS cases (20%); p21 was expressed
      in all cases. Loss of Bax was observed in 3 AVS and 3 UVS cases. The anti
      apoptotic protein, Bcl-2, was expressed in 9 AVS (75%) and 11 UVS (73%), and p53,
      Fas-L, and caspase 3 were negative and Fas was positive in all AVS and UVS cases.
      Of these, only the loss of p27 was statistically significant (P = 0.02). The loss
      of p27 in AVS may explain the unusually high proliferative potential of AVS
      versus UVS, and p27 may be a predictor of VS aggressiveness. The expressions of
      other apoptosis associated proteins were not significantly different in the two
      groups. This may be the first report to identify a molecular entity associated
      with aggressive VS. However, further studies are required.

PMID- 16283444
TI  - Pathological changes after radiotherapy for primary pituitary carcinoma: a case
      report.
AB  - Pituitary carcinomas are extremely rare. The definition, diagnosis, therapy, and
      prognosis are controversial. So far, to our knowledge, there has been no report
      regarding pathological changes after radiotherapy for primary pituitary
      carcinoma. We reported a single case of a presumed prolactin staining pituitary
      carcinoma. We defined carcinoma by premorbid intracranial dissemination of the
      tumor. There were no proven extracranial metastases. The tumor was silent on PET
      scanning. The patient received external beam radiotherapy alone as primary
      therapy. Post-irradiation histology revealed that necrotic tissue made up
      approximately more than half. Tumor had viable cells. Probably approximately
      three-fifth of tumor cells were without alteration and approximately two-fifth
      were with degeneration. We confirmed that necrosis but no apoptosis were
      coexistent in the cells post irradiation for pituitary carcinoma.

PMID- 16283446
TI  - MALT lymphoma presenting as a meningioma.

PMID- 16283445
TI  - Systemic temozolomide combined with loco-regional mitoxantrone in treating
      recurrent glioblastoma.
AB  - Twenty-two recurrent GBM patients were enrolled for second tumor debulking with
      local positioning of a Rickam reservoir, in order to locally deliver chemotherapy
      with the aim of controlling local tumor recurrence. We designed a protocol using
      systemic temozolomide (150 mg/sqm days 1-5 every 28) in association with
      mitoxantrone, delivered through the reservoir (4 mg/day 1-5 every 28) positioned
      into the area of tumor exeresis. After re-operation a residual tumor mass no
      larger than 2 cm was identified in 18/22 patients. The patients were treated with
      monthly cycles of chemotherapy until evolution of the tumor, but in no case for
      more than 10 cycles. Responses were evaluated by MRI scans performed every 2
      months and images assessed according to MacDonald's criteria. Response rate: no
      complete responses (CR), 5 partial responses (PR), 13 stable disease (SD) and 4
      progressive disease (PD) occurred. The median progression-free survival (PFS) and
      survival time (ST) of the whole group of treated patients was 7 and 11 months,
      respectively and more than a quarter of the patients survived over 18 months.
      During the study, the patients' compliance was complete and no dropouts occurred.
      Hematological toxicity was mild and after repeated local injections only minor
      neurological side-effects occurred. Despite some bias in patients' selection not
      excluded in this pilot study, results are interesting: the PFS was as long as the
      survival of recurrent GBM reported in the literature.

PMID- 16283447
TI  - Neurofibromatosis I and unexplained iron deficiency in two patients: is iron
      depletion related to neurofibroma growth?

PMID- 16283448
TI  - Paraneoplastic limbic encephalitis presenting as acute viral encephalitis.
AB  - OBJECTIVE: To describe a case of limbic encephalitis which initially presented as
      viral limbic encephalitis and during the clinical evaluation a renal carcinoma
      was diagnosed. CASE REPORT: Patient with history of peripheral paresis of right
      facial nerve, 1 month after symptoms appearance and treatment, developed fever,
      vomiting, grand mal seizure, decreased level of consciousness, confusion,
      hallucinations and agitation. The patient initially presented a clinical picture
      of viral LE. which confirmed by CSF. MRI brain showed areas with pathological
      intensity signal in the region of limbic system unilateral. During the clinical
      evaluation a renal carcinoma was discovered and a nephrectomy has been performed.
      CONCLUSIONS: Although PLE typically presents as a chronic or subacute disease, it
      may be fulminant and clinically indistinguishable from an acute HSVE. This
      association pose the problem of a possible relation between this two syndromes
      and the correct diagnosis is very important, because there are effective
      treatments.

PMID- 16283450
TI  - Ecophysiological factors affecting growth, sporulation and survival of the
      biocontrol agent Penicillium oxalicum.
AB  - The effect of temperature, pH, water potential and sources of nitrogen and carbon
      on the biocontrol agent Penicillium oxalicum were studied in vitro. The fungus is
      xerotolerant, mesophillic and has a wide pH tolerance. The parameters evaluated
      (germination, germ tube length, growth rate and sporulation) showed different
      sensitivities to the environmental factors. Peptone and free amino acids gave the
      highest growth rates and high levels of sporulation. Xylose, mannose and fructose
      gave the highest growth rates and mannose induced strong sporulation. The effect
      of nutrients (mannose + arginine) and water potential was also studied in vivo.
      The xerotolerant character of the fungus was confirmed. From this study we
      consider Penicillium oxalicum ecologically competent to perform effectively as a
      biocontrol agent in the soil environment.

PMID- 16283451
TI  - Effect of selenite and tellurite on the morphological growth and toxin production
      of Aspergillus parasiticus var. globosus IMI 120920.
AB  - Aspergillus parasiticus var. globosus IMI 120920 was able to grow in presence of
      different concentrations tested (0.052-4.0%) of sodium selenite or concentrations
      up to 2.0% potassium tellurite. Growth of the fungus was decreased greatly by the
      increase of metals concentrations. Dark colour colony and black reverse were
      formed in presence of tellurite while reddish gray to grayish red colony colour
      and brownish red to orange red reverse were formed in presence of selenite. The
      fungal biomass was slightly decreased at lower concentrations and highly
      inhibited at higher concentrations of selenite or tellurite. Selenite slightly
      stimulated aflatoxin formation at lower concentrations and highly inhibited it at
      higher concentrations. Aflatoxin production was decreased greatly by increasing
      tellurite concentrations. Obvious malformations were observed in the
      morphological features of the fungus in presence of different levels of selenite
      or tellurite.

PMID- 16283452
TI  - Sem study on the invasion of Nomuraea rileyi (Farlow) on silkworm, Bombyx mori
      Linn. causing green muscardine.
AB  - The mature conidia of Nomuraea rileyi (Farlow) germinate on the larval integument
      of Bombyx mori within 24 h and penetrate the cuticle within 36 h after
      inoculation at 24.0 +/- 1.0 degrees C temperature and 80.0 +/- 5.0% relative
      humidity. The penetrating hyphae multiply by budding and septa formation in the
      hemocoel, and the larva succumbs to the infection 6-7 days post-treatment. The
      hyphal bodies elongate and become interwoven with other hyphae forming a mycelial
      complex across different tissues. The ramification of hyphae along the epidermal
      tissue results in larval mummification in 7-8 days. Numerous conidiophores
      emerge, producing a confluent white fungal mat over the entire surface of the
      host larva by 9-10 days. Pale green conidia develop, making the larval body
      green. Life cycle of the fungus on B. mori is completed in 10-11 days.

PMID- 16283453
TI  - Laccase activity of lignicolous aquatic hyphomycetes isolated from the River Nile
      in Egypt.
AB  - Eleven species of aquatic hyphomycetes were isolated from 92 samples of different
      lignin sources (unidentified wood segments, skeleton and neck of leaves, bark).
      The most common species were Pyramidospora casuarina (on 3.7% of samples),
      Triscelophorus monosporus (3.2%) and Flagellospora curvula (3%). Varying levels
      of laccase activity were present in most of the fungi included in this study. The
      laccase plate assay was found to be much less reliable than the
      spectrophotometric assay. Several factors including type of growth medium, the
      media pH and assay pH had marked effects on laccase activity. A few species
      produced high levels of laccase in both malt extract (ME) medium and low N
      medium; however, a majority of the species produced laccase in low nitrogen (N)
      medium (pH 4.5) but not in the ME medium. When the tested species were grown in
      low N medium at pH 4.5, six species showed acidic laccase (pH 4.5) activity; of
      these, four also showed alkaline laccase (pH 8.2) activity. Alatospora acuminata
      and Tetracladium marchalianum exhibited laccase activity only when grown in the
      low N medium at pH 8.2. These results indicate that aquatic hyphomycetes may play
      a role in the decomposition of lignin materials in freshwater environments.

PMID- 16283454
TI  - Effect of temperature on antagonistic and biocontrol potential of Trichoderma sp.
      on Sclerotium rolfsii.
AB  - Sclerotium rolfsii is a destructive soil-borne and post-harvest plant pathogen.
      Use of the antagonistic fungus Trichoderma sp. has been earlier reported by us to
      successfully control this pathogen under post-harvest conditions. In the present
      paper we report on the effects of temperature on the growth and biocontrol
      potential of Trichoderma sp. on S. rolfsii. Experimental results indicated that
      S. rolfsii and Trichoderma sp. have different temperature optima for growth: 30
      35 degrees C for the pathogen and 25-30 degrees C for the antagonist. In dual
      culture, Trichoderma over-grew S. rolfsii at 25 degrees C and 30 degrees C, but
      at 35 degrees C and 37 degrees C, S. rolfsii over-grew the colony of Trichoderma.
      Trichoderma produced higher concentration of fungi-toxic metabolites in broth
      culture at higher temperatures. In bioassays using ginger slices and whole
      rhizomes, it has been demonstrated that Trichoderma is not very effective in
      suppressing S. rolfsii at temperatures above 30 degrees C. In light of these
      results, possible mechanisms of biocontrol of S. rolfsii as a post-harvest
      pathogen has been discussed. Storage temperature has been suggested as a critical
      factor in biocontrol of S. rolfsii.

PMID- 16283455
TI  - Hyperparasites of the genus Ampelomyces on powdery mildew fungi in Serbia.
AB  - From 1982 to 1996, in Serbia, 229 species of plants infected with powdery mildew
      were collected. Seventy-five species had hyperparasites of the genus Ampelomyces.
      Distribution analysis showed that hyperparasitism was greatest on plants from the
      families Asteraceae, Apiaceae and Fabaceae. Ampelomyces was not found on the
      family Poaceae. It was reported for the first time on the families Amygdalaceae,
      Cornaceae, Grossulariaceae, Plantaginaceae, Rhamnaceae and other 37 plant
      species. Hyperparasites of the genus Ampelomyces were found on 33 different
      species of fungi that are causal agents of powdery mildews. They are reported for
      the first time on nine species. Pycnidial size varied in the range 45-106 x 25.5
      40.5 microm and conidia from 4.5-10.5 x 2.5-4.8 microm.

PMID- 16283456
TI  - Fusaria and Fusarium toxins in New Zealand maize plants.
AB  - A time course study was made of the development of Fusarium infection and the
      appearance of the three Fusarium toxins, nivalenol (NV), deoxynivalenol (DON) and
      zearalenone (ZEN), in various fractions of maize plants from two sites in New
      Zealand, one in the Manawatu region and one in the Waikato. Fusarium infection
      was seen in leaf axil fractions in January, at the time of tassel emergence, and
      was detectable in stalks, leaf blades, rachis and peduncles during February and
      in kernels in April. NV, DON and ZEN were only detectable some time after
      infection was demonstrable. NV, in high concentrations relative to DON (up to 287
      mg/kg for NV and up to 8 mg/kg for DON), was found in fractions from the Manawatu
      site where F. crookwellense and F. culmorum were the predominant toxigenic
      species. NV and DON at similar levels (up to 25 mg/kg) were found in fractions
      from the Waikato site at which F. graminearum and F. subglutinans predominated.
      Highest levels of NV and DON were in rachis and peduncle. ZEN was found most
      consistently in leaf axils and blades at both sites (up to 8 mg/kg at the
      Manawatu site and up to 75 mg/kg at the Waikato site) but at times there were
      high levels in rachis fractions (up to 417 mg/kg at the Manawatu site).

PMID- 16283457
TI  - Effect of environmental conditions and inoculum density on infection of guava
      fruits by Colletotrichum glososporioides.
AB  - The influence of environmental factors (temperature and humidity), inoculum
      density on infection by Colletotrichum glososporioides and development of
      anthracnose lesions were determined on uninjured, sand-injured and punctured
      fruits. The optical temperature for severe infection was 30 degrees C, whereas
      the disease incidence was less at 20 and 35 degrees C. Inoculated guavas that
      received 1-60 h of continuous free moisture developed lesions, but the disease
      was minimal (0-7%) after 1-6 h free moisture. Infection rates of uninjured, sand
      injured and punctured fruits receiving 60 h of free moisture were 34, 70 and
      100%, respectively. Disease incidence increased as inoculum density increased
      from 101 to 106 conidia/ml. In field conditions, the development of anthracnose
      lesions was greater on punctured guavas than on uninjured or sand-injured ones,
      in both rainy and winter seasons. In general, the number of lesions was highest
      in sand-injured fruits, followed by punctured and uninjured fruits. In rainy
      season the number of lesions on injured and uninjured fruits was greater than
      similarly treated guavas in winter.

PMID- 16283458
TI  - Malachite green agar, a new selective medium for Fusarium spp.
AB  - Malachite Green Agar 2.5 ppm (MGA 2.5) is a potent selective medium for isolation
      and enumeration of Fusarium spp. It has been tested with pure and mixed cultures
      as well as in naturally contaminated samples. The recoveries of Fusarium species
      in MGA 2.5 were the same as the recoveries obtained in Nash and Snyder medium.
      However, this medium is a more selective culture medium for Fusarium spp. than
      Nash and Snyder medium, because it does not allow the development of colonies
      belonging to other fungal genera. MGA 2.5 is simple to prepare and less hazardous
      than other Fusarium selective media containing pentachloronitrobenzene (PCNB).

PMID- 16283459
TI  - Natural occurrence of Fusarium toxins in barley harvested during five years in an
      area of southwest Germany.
AB  - A total of 44, 40, 47, 51, and 58 barley samples for feed use were collected
      randomly after the 1987, 1989, 1990, 1991, and 1992 crops, respectively, from
      farms located in an area of southwest Germany. The sum of precipitation from May
      to September was high in 1987 and markedly lower in 1989-1992. Deoxynivalenol, 3
      . and 15-acetyldeoxynivalenol, nivalenol, fusarenon-X, T-2 toxin, HT-2 toxin and
      diacetxyscirpenol were determined by gas chromatography with mass selective
      detection (GC-MS), zearalenone,alpha- and beta-zearalenol by GC-MS or by HPLC.
      Deoxynivalenol was the major toxin with incidences at 71-98% and mean contents at
      42-400 microg/kg. In contrast, incidences of zearalenone, 3-acetyldeoxynivalenol,
      nivalenol, HT-2 toxin, and T-2 toxin were at 7-68, 7-48, 11-41, 0-9, and 2-29%,
      respectively; with mean contents at 3-146 microg/kg. alpha- and beta-zearalenol
      and diacetoxyscirpenol were not detected in any sample. 15-acetyldeoxynivalenol
      and fusarenon-X were assayed in samples from 1987, 1991 and 1992. 15
      acetyldeoxynivalenol was detected in 30, 0 and 2% of samples, respectively, with
      an average content of positive samples at 8 and 4 microg/kg, fusarenon-X was not
      detected. Over the years, incidences and levels of toxins remained constant,
      decreased or increased. The correlation between the occurrence of toxins and
      level of precipitation is discussed.

PMID- 16283467
TI  - Idealism and ethics of public-health practitioners.

PMID- 16283468
TI  - Ganges, Cambridge, Chicago, Edinburgh, Cambridge... Values and public health.

PMID- 16283469
TI  - Postmodernism versus idealism in public health.

PMID- 16283470
TI  - Although some humans are rats, not all rats are human.

PMID- 16283471
TI  - Kos, Dresden, Utopia... A journey through idealism past and present in public
      health.
AB  - This essay reviews some of the sources of idealism in public health, on the basis
      of an intellectual journey to Kos (home to Hippocrates and his altruistic
      legacy), Dresden (where the Deutsches Hygiene Museum illustrates the historical
      connections between fascism and public health), and Utopia (exemplified by
      Etienne Cabet's Icarie, a fantasy of an ideal city which has nevertheless been
      partly realized). It is suggested that the large-scale altruism of public health
      has to be balanced with the value of individual autonomy, and that some degree of
      dreaming of a better and healthier world is indispensable for further progress in
      public health. The main conclusion is that the ethical foundations of public
      health are not always self-evident, and that critical reflection on these
      foundations was, is, and will always be necessary.

PMID- 16283472
TI  - Consistency of epidemiologic estimates.
AB  - BACKGROUND: The epidemiology of a disease describes numbers of people becoming
      incident, being prevalent, recovering, surviving, and dying from the disease or
      from other causes. As a matter of accounting principle, the inflow, stock, and
      outflows must be compatible, and if we could observe completely every person
      involved, the epidemiologic estimates describing the disease would be consistent.
      Lack of consistency is an indicator for possible measurement error. METHODS: We
      examined the consistency of estimates of incidence, prevalence, and excess
      mortality of dementia from the Rotterdam Study. We used the incidence and excess
      mortality estimates to calculate with a mathematical disease model a predicted
      prevalence, and compared the predicted to the observed prevalence. RESULTS:
      Predicted prevalence is in most age groups lower than observed, and the
      difference between them is significant for some age groups. CONCLUSIONS: The
      observed discrepancy could be due to overestimates of prevalence or excess
      mortality, or an underestimate of incidence, or a combination of all three. We
      conclude from an analysis of possible causes that it is not possible to say which
      contributes most to the discrepancy. Estimating dementia incidence in an aging
      cohort presents a dilemma: with a short follow-up border-line incident cases are
      easily missed, and with longer follow-up measurement problems increase due to the
      associated aging of the cohort. Checking for consistency is a useful strategy to
      signal possible measurement error, but some sources of error may be impossible to
      avoid.

PMID- 16283473
TI  - Collecting saliva by mail for genetic and cotinine analyses in participants
      recruited through the Internet.
AB  - The authors assessed whether collection by mail of saliva and buccal cells for
      genetic analysis was feasible in participants recruited through the Internet. In
      2003, 14,773 visitors of a smoking cessation website were invited by e-mail to
      take part in the study. Salivettes (plastic vials containing a cotton roll) were
      mailed to participants, for collection of saliva and buccal cells. Because of
      limited resources, the authors stopped recruitment when 392 participants (3% of
      14,733) were registered. They received 315 saliva samples back (80% of 392).
      Salivary cotinine was analyzed in 145 daily smokers. Cotinine concentration could
      be assessed in 141 samples (97%) (range 0.7-899 ng/ml, median 260 ng/ml). DNA
      extraction was achieved in all the 285 samples in which it was attempted. Quality
      of DNA was assessed by optical density measurements and by polymerase chain
      reaction amplification of a gene coding for the alpha-4 nicotinic receptor, with
      the detection of a known polymorphism. Successful results were obtained in 235
      samples (82% of 285). Thus collecting saliva by mail for cotinine and DNA
      analysis in participants recruited through the internet produced samples of good
      quality at a reasonable cost. This approach should be valuable for genetic
      epidemiology and pharmacogenetic research.

PMID- 16283474
TI  - Determinants of response in a longitudinal health study following the firework
      disaster in Enschede, The Netherlands.
AB  - Very few longitudinal health studies after disasters published data on the
      determinants of loss to follow up. However, these determinants provide important
      information for future disaster studies to improve their response and reduce
      selection bias. For this purpose we analyzed the data of a longitudinal health
      survey which was performed among residents and emergency workers, at 3 weeks (n =
      3662) and at 18 months (n = 2769) after a major firework disaster in The
      Netherlands (Enschede, May 13, 2000). The response was lower among immigrants
      (54%) than among native Dutch (81%). Severe damage to the house due to the
      disaster (OR: 1.8; 95% CI: 1.1-3.0) and being involved as an emergency workers
      (OR: 2.1; 95% CI: 1.2-3.4) were associated with higher response among native
      Dutch, while this was not the case among immigrants. Non-western immigrants with
      health problems in the first study were more likely to participate in the second
      study (for example physical symptoms OR: 2.5: 95% CI: 1.4-4.4), while the native
      Dutch with these symptoms were less likely to participate (OR: 0.7; 95% CI: 0.5
      0.9). In conclusion, disaster-related characteristics were associated with higher
      response in native Dutch. Health problems were associated with higher response
      among non-western immigrants and with lower response among the native Dutch.

PMID- 16283475
TI  - Mortality spike at New Year but not Christmas in North East England.
AB  - Mortality in the USA has been shown to spike on Christmas and New Year's Day. No
      comparable analyses are available for European data despite recognised seasonal
      mortality variations. Deaths for 1986-2000 were analysed by date for Newcastle
      and North Tyneside (NNT) to examine the Christmas period and the weeks
      surrounding Easter. A spike in mortality attributable to increases in cardiac and
      respiratory deaths was seen on New Year's Day but not on Christmas Day. No
      disturbance of trend was seen at Easter. The causes of the 'holiday phenomenon'
      are not understood, but absence of a Christmas spike in NNT may indicate that it
      is preventable.

PMID- 16283476
TI  - Systemic sclerosis mortality in the United States: 1979-1998.
AB  - The US national mortality rates from systemic sclerosis (SSc) have not been
      reported since 1979. We studied age, gender and race specific time trends in US
      national mortality rates of SSc during the period 1979-1998 using poisson
      regression models. Over the 4.93 billion person-years of observation during the
      study period, there were 18,126 deaths from SSc, representing a mortality rate of
      3.9 per million. The age adjusted mortality rates for men and women were 1.9 and
      5.4 per million respectively. There were relatively few deaths in the extremes of
      age. SSc mortality rates increased with age in both genders and in all racial
      groups (p<0.001). In multivariable models adjusted for two-way statistical
      interactions, being African-American, female and of older age were associated
      with higher death rates. Over the 20 years of observation, overall (age-adjusted)
      SSc mortality rates showed a 36% increase (p<0.001) and subgroup analyses
      revealed that the increases were confined to women of both races. This rise
      occurred during a period in which post-diagnosis survival of SSc is known to have
      increased, suggesting an increasing incidence of this disease.

PMID- 16283477
TI  - All-cause mortality and mortality of myocardial infarction for 989 legally
      castrated men.
AB  - BACKGROUND: Male gender is an independent coronary risk factor. METHOD: Long-term
      follow-up of 989 Danish men who underwent legal castration between 1929 and 1968.
      RESULTS: The legally castrated men were unmarried and belonged to social class IV
      and V more often than were Danish men in general. During the follow-up until
      2000, 835 of the 989 (85%) castrated men died, including 148 who died of
      myocardial infarction. In multiple Poisson regression analyses, the men had a
      standardized mortality rate (SMR) for all-cause mortality of 1.30 (95% CI: 1.26
      1.36) and a SMR for mortality of myocardial infarction of 1.08 (95% CI: 1.04
      1.16). Thus, the castrated men had a lower proportion of deaths of myocardial
      infarction (148/792, 18.7% (95% CI: 16.0-21.6%)) than was expected based on the
      mortality rates for the Danish male population (136/608, 22.4%). The castrated
      men had discordant changes for the SMR for all-cause mortality and mortality of
      myocardial infarction whereas subgroups of the Danish population previously has
      been found to have concordant changes for the two SMRs. CONCLUSION: The castrated
      men had fewer deaths of myocardial infarction than expected, so men may not have
      increased risk of coronary heart disease from unphysiologically low levels of
      endogenous androgens.

PMID- 16283478
TI  - Risk factors for hip fracture and a possible effect modification by hormone
      replacement therapy. The Danish nurse cohort study.
AB  - OBJECTIVE: To identify risk factors for hip fracture and to examine whether
      hormone replacement therapy (HRT) modifies the effect of these risk factors.
      DESIGN: Prospective cohort study. SETTING: The Danish Nurse Cohort Study.
      PARTICIPANTS: 14,015 female nurses aged 50 years and above who in 1993 completed
      a questionnaire on general health and lifestyle issues, reproductive history
      including information on HRT, and family history of osteoporosis and personal
      history of a wrist fracture. OUTCOME MEASURES: End-point was the first-ever hip
      fracture registered in the Danish National Hospital Register during the period
      from 1993 to 1999. RESULTS: During the follow-up period 245 hip fractures were
      identified. Ever users of HRT had a lower risk of hip fracture (hazard ratio
      0.69; 0.50-0.94). Women reporting a poor health (hazard ratio 2.01; 1.30-3.11),
      restrictions in daily activities (hazard ratio 1.52; 1.05-2.21), low body mass
      index (hazard ratio 1.65; 0.98-2.77), and leisure time sedentary physical
      activity (hazard ratio 1.88; 1.30-2.70) were main identified risk factors for hip
      fracture. HRT did not modify the effect of risk factors on the risk of hip
      fracture. CONCLUSION: This study confirms that women with a frail health are at
      increased hip fracture risk and that ever use of HRT decreases the risk of hip
      fracture. HRT did not modify the effect of these risk factors, indicating that
      the preventive effect of this therapy is independent of risk factors.

PMID- 16283479
TI  - Epidemiology of tuberculosis in the Southeastern Iran.
AB  - In order to study the epidemiology of tuberculosis (TB) in Zabol, situated in the
      Southeast of Iran, this study was performed. Two thousand seven hundred and
      twenty-nine cases of tuberculosis disease were identified during 1998-2002. The
      notification rate was 135/100,000 population in 2002, which was higher than this
      rate in previous years. The notification rate of TB in Afghan population was
      significantly higher than Iranian population (202 cases/100,000 in Afghan and 122
      cases/100,000 in Iranian population. The case notifications in 1998-2001 were
      134, 131, 130, and 130 in 100,000 populations, respectively. The prevalence of
      smear-positive cases was 76/100,000 population in 2002 and the ratio of smear
      positive cases to smear-negative and extrapulmonary cases was 1.46. This region
      remains high TB rates. It is necessary to pay attention to the detection of TB,
      by making their register in order to enhance the effectiveness and to reduce the
      cost of existing methods.

PMID- 16283480
TI  - KiSS1 suppresses metastasis in human ovarian cancer via inhibition of protein
      kinase C alpha.
AB  - Metastasis is a vital target for cancer treatment, since the majority of cancer
      patients die from metastatic, rather than the primary disease. KiSS1 has been
      identified as a metastasis suppressor gene in melanoma and breast carcinomas. We
      show here that KiSS1 is also a metastasis suppressor in human ovarian cancer.
      Overexpression of KiSS1 in ovarian cancer cells inhibits cell migration induced
      by serum or lysophosphatidic acid (LPA), and colonization in soft agar, but not
      cell proliferation, representing the characteristics of a metastasis suppressor
      gene. Furthermore, using an experimental metastatic mouse model, we show that
      expression of KiSS1 in SKOV3 ovarian cancer cells suppresses >50% metastatic
      colonization in mice (P < 0.0001). We find that activating protein kinase C (PKC)
      reverses about 80% of the inhibited cell migration induced by KiSS1, while down
      regulation of PKCalpha with shRNA restores KiSS1 effect, providing evidence that
      inhibiting PKCalpha may be an important mechanism of the effect of KiSS1. These
      results suggest that KiSS1 is a metastasis suppressor of ovarian cancer and may
      be a potential molecular target for the treatment.

PMID- 16283481
TI  - Perlecan knockdown in metastatic prostate cancer cells reduces heparin-binding
      growth factor responses in vitro and tumor growth in vivo.
AB  - Perlecan (Pln) is a major heparan sulfate proteoglycan (HSPG) of extracellular
      matrices and bone marrow stroma. Pln, via glycosaminoglycans in domains I and V,
      acts as a co-receptor for delivery of heparin binding growth factors (HBGFs) that
      support cancer growth and vascularization. Specifically, glycosaminoglycans bind
      HBGFs and activate HBGF receptors, including those for FGF-2 and VEGF-A. The
      contribution of Pln to prostate cancer growth was tested using a ribozyme
      approach to knockdown Pln expression levels. Transfection into the androgen
      independent, bone targeted prostate cancer line, C4-2B, and efficient stable
      knockdown of Pln was demonstrated by quantitative PCR, immunohistochemistry and
      immunoblotting. Three individually isolated subclones with 75-80% knockdown in
      Pln mRNA, protein expression and secretion into ECM were used to study in vitro
      growth responses to FGF-2 and VEGF-A. While cells with normal Pln levels
      responded to both HBGFs, knockdown cells responded poorly. All lines responded to
      serum growth factors and IGF-I. Anchorage-independent growth assays showed
      reduced colony size and cohesiveness by all Pln deficient subclones compared to
      parental C4-2B cells. In vivo effects of Pln knockdown were measured by
      inoculating knockdown and control ribozyme transfected cell lines into athymic
      mice. A reduced growth rate, smaller tumor size, diminished vascularization and
      failure to elevate serum PSA characterized mice bearing Pln knockdown C4-2B
      cells. Poor vascularization correlated with reduced levels of VEGF-A secreted by
      Pln knockdown lines. We conclude that Pln is an essential ECM component involved
      in growth responses of metastatic prostate cancer cells to HBGFs deposited in
      local and metastatic microenvironment.

PMID- 16283482
TI  - Role of integrin receptors for fibronectin, collagen and laminin in the
      regulation of ovarian carcinoma functions in response to a matrix
      microenvironment.
AB  - Integrins play an important role in cellular matrix interactions requisite for
      cancer cell adhesion, growth, migration and invasion. In this study, we have
      investigated the expression of integrin subunits alpha3, alpha6, alphav and beta1
      in normal ovaries, benign ovarian tumors and ovarian carcinomas of different
      pathological grades. The expression of these integrins in ovarian cancer cell
      lines was also investigated, and their role in sustaining proliferation,
      adhesion, migration and invasion in cohort with the activation of signaling
      pathways in response to extracellular matrices (ECM) was evaluated. We
      demonstrate a differential expression pattern of alpha3, alpha6, alphav and beta1
      integrin subunits in ovarian carcinomas compared to normal ovaries and benign
      ovarian tumors. Ovarian cancer cell lines (Hey, Ovcar3 and Peo.36) demonstrated
      significantly high expression of alpha3, alpha6, alphav and beta1 integrin
      subunits. A significant increase in proliferation and adhesion (P<0.05) in
      response to collagen 1 (Coll) and laminin (LM), ligands for integrin receptor
      alpha3beta1 and alpha6beta1 was observed in ovarian cancer cell lines. On the
      other hand, fibronectin (FN), a receptor for alphavbeta1 integrin, increased
      proliferation in all ovarian cancer cell lines studied but only enhanced adhesion
      in Hey cell line (P<0.05). Neutralizing antibodies against alpha3, alpha6, alphav
      and beta1 integrin subunits inhibited ECM-induced proliferation, but increased
      adhesion to ECM was inhibited by beta1 integrin subunit antibody. No suppression
      of Coll, LM and FN-induced (Hey cells only) adhesion was observed in the presence
      of alpha3 or alphav subunit antibodies but LM-induced adhesion was inhibited by
      blocking alpha6 subunit functions. LM, FN and Coll enhanced chemotactic migration
      in Hey cells, but direct invasion across ECM was observed only in the presence of
      LM and Coll. Blocking antibodies against alpha3, alpha6 and beta1 integrin
      subunits inhibited both chemotactic migration and invasion of Hey cells in
      response to respective ECM. Adhesion of ovarian cancer cells to FN, Coll and LM
      activated Ras, Erk and Akt pathways. Neutralizing alphav and beta1 functions did
      not inhibit FN-induced activation of Ras and Erk pathways but inhibited the Akt
      pathway. On the other hand, antibodies against alpha6 and beta1 subunits, but not
      alpha3 subunit, inhibited LM-induced activation of Ras but did not inhibit the
      downstream Akt pathway. Neutralizing beta1 subunit function however, inhibited LM
      induced Erk activation. Coll-induced activation of Ras, Erk and Akt pathways was
      inhibited by alpha3 and beta1 integrin subunit antibodies. These results indicate
      that alpha3beta1, alphavbeta1 and alpha6beta1 integrin mediate proliferation,
      adhesion, migration and invasion of ovarian cancer cells in response to ECM and
      targeting these integrins to modulate integrin-ECM interactions in tumor cells
      may be a promising tool to reduce the dissemination of ovarian carcinoma in vivo.

PMID- 16283483
TI  - MRI detection of early bone metastases in b16 mouse melanoma models.
AB  - Bone metastasis causes significant morbidity in cancer patients, including bone
      pain, pathologic fractures, nerve compression syndrome, and hypercalcemia. Animal
      models are utilized to study the pathogenesis of skeletal metastases and to
      evaluate potential therapeutic agents. Previously published methods for imaging
      bone metastasis in rodent models have focused on identifying advanced stage
      metastasis using simple X-rays. Here we report MRI as a method for detecting
      early bone metastases in mouse models in vivo. B16 mouse melanoma cells were
      injected into the left cardiac ventricle of C57BL/6 mice and magnetic resonance
      (MR) images were obtained of the left leg following the development of metastatic
      disease, when tumor associated bone destruction was histologically present but
      not visible by X-ray. T1 and T2 relaxation times of bone marrow were measured in
      healthy control mice and B16 melanoma tumor-bearing mice. Mean T2 values for
      normal marrow were 28 ms (SD 5) and for diseased bone marrow were 41 ms (SD 3).
      T2 relaxation time of diseased bone marrow is significantly longer than that of
      normal bone marrow (P < 0.0001) and can be used as a marker of early bone
      metastases. These studies demonstrate that MR imaging can detect bone marrow
      metastases in small animals prior to development of cortical bone loss identified
      by X-ray.

PMID- 16283484
TI  - Enhancement of nitric oxide release in mouse inflammatory macrophages co
      cultivated with tumor cells of a different origin.
AB  - In the present study we investigated whether synthesis of nitric oxide (NO) by
      macrophages is affected by contact with tumor cells. Although it is well known
      that NO generated by macrophages influences different activities related to tumor
      progression, there is limited information on the modulatory role of tumor cells
      on NO release by macrophages. The experimental protocol used in our study
      consisted in the determination of NO secreted by macrophages, either resident or
      inflammatory, co-cultivated with tumor cells (B16 melanoma and L929 fibrosarcoma
      cells) at different cell densities and macrophage:tumor cell ratios. This
      experimental in vitro protocol simulates the different interactions between
      macrophages and tumor cells that occur during the development of a tumor mass. We
      found that the co-cultivation with tumor cells induced an increased secretion of
      NO in macrophages provided that they express an inflammatory phenotype, and they
      were challenged with LPS or IFNgamma/LPS. Two more variables were found to be
      critical in the increase of NO generation in inflammatory macrophages cultivated
      with tumor cells: a high cell density and a prevalence of tumor cells over
      macrophages. The enhancement of NO secreted in inflammatory macrophages
      stimulated by tumor cells was not observed in normal murine fibroblasts co
      cultivated with tumor cells.

PMID- 16283485
TI  - Genetic and pathologic changes associated with lymphovascular invasion of
      colorectal adenocarcinoma.
AB  - Lymphovascular invasion (LVI) is a biological manifestation of aggressive
      behavior in colorectal cancer. This study sought to identify and examine the
      association between genetic and pathologic alterations implicated in this
      invasive tumor progression. We consecutively recruited 81 and 79 colorectal
      cancer patients with and without LVI, respectively. Biological changes were
      evaluated by clinicopathological parameters together with CEA and E-cadherin
      expressions using immune staining. Allelic loss or MSI was examined using 10
      microsatellite markers on chromosomes 10, 16, 18, and TGFbetaRII, possibly
      associated with colorectal cancer. The germline mutation of BMPR1A and SMAD4 was
      also sought. Tumor stage and lymph node metastasis were significantly greater in
      patients with LVI tumor than without it (P < 0.001). Decreased CEA expression was
      closely correlated with allelic loss or MSI at D16S421, D18S46, and D18S474 (P =
      0.004-0.047). Allelic loss at D10S14 was specific to LVI tumors (P = 0.007).
      Using multivariate analysis, allelic loss at D18S46 significantly correlated with
      histological differentiation (P = 0.02). In addition, allelic loss and MSI at
      D18S474, histological differentiation, and expression of CEA and E-cadherin were
      closely associated with the progression of LVI (P = 0.005-0.049). However, no
      germline mutation in BMPR1A or SMAD4 was detected in all patients regardless of
      LVI status. In summary, in a subset of colorectal cancers, histological
      differentiation and expression of CEA or E-cadherin appear to determine
      aggressive behavior such as LVI. These changes are closely associated with
      chromosomal alterations at 10q22-23, 16q22 and 18q21, which carry several tumor
      suppressor genes.

PMID- 16283486
TI  - A PSP94-derived peptide PCK3145 inhibits MMP-9 secretion and triggers CD44 cell
      surface shedding: implication in tumor metastasis.
AB  - PURPOSE: PCK3145 is a synthetic peptide corresponding to amino acids 31-45 of
      prostate secretory protein 94, which can reduce experimental skeletal metastases
      and prostate tumor growth in vivo. Part of its biological action involves the
      reduction of circulating plasma matrix metalloproteinase (MMP)-9, a crucial
      mediator in extracellular matrix (ECM) degradation during tumor metastasis and
      cancer cell invasion. The antimetastatic mechanism of action of PCK3145 is
      however, not understood. EXPERIMENTAL DESIGN: HT-1080 fibrosarcoma cells were
      treated with PCK3145, and cell lysates used for immunoblot analysis of small
      GTPase RhoA and membrane type (MT)1-MMP protein expression. Conditioned media was
      used to monitor soluble MMP-9 gelatinolytic activity by zymography and protein
      expression by immunoblotting. RT-PCR was used to assess RhoA, MT1-MMP, MMP-9,
      RECK, and CD44 gene expression. Flow cytometry was used to monitor cell surface
      expression of CD44 and of membrane-bound MMP-9. Cell adhesion was performed on
      different purified ECM proteins, while cell migration was specifically performed
      on hyaluronic acid (HA). RESULTS: We found that PCK3145 inhibited HT-1080 cell
      adhesion onto HA, laminin-1, and type-I collagen suggesting the common
      implication of the cell surface receptor CD44. In fact, PCK3145 triggered the
      shedding of CD44 from the cell surface into the conditioned media. PCK3145 also
      inhibited MMP-9 secretion and binding to the cell surface. This effect was
      correlated to increased RhoA and MT1-MMP gene and protein expression.
      CONCLUSIONS: Our data suggest that PCK3145 may antagonize tumor cell metastatic
      processes by inhibiting both MMP-9 secretion and its potential binding to its
      cell surface docking receptor CD44. Such mechanism may involve RhoA signaling and
      increase in MT1-MMP-mediated CD44 shedding. Together with its beneficial effects
      in clinical trials, this is the first demonstration of PCK3145 acting as a MMP
      secretion inhibitor.

PMID- 16283487
TI  - Modification of an in vivo lung metastasis model of hepatocellular carcinoma by
      low dose N-nitrosomorpholine and diethylnitrosamine.
AB  - Previously, we established the in vivo lung metastasis model of rat HCC induced
      by two hepatocarcinogens, diethylnitrosamine (DEN) and N-nitrosomorpholine (NMOR)
      at a dose of 120 ppm. This model allows us to investigate modifying factors
      leading to the inhibition of metastasis formation. However, low survival rates
      made the evaluation of metastasis formation difficult. The current experiments
      were conducted to modify the experimental protocol to improve survival and to
      establish a better animal metastasis model. Lower doses of NMOR (80 or 40 ppm in
      drinking water) were given to F344 rats for 14 weeks after DEN treatment.
      Survival rates in the 80 ppm group and in the 40 ppm group were 57% and 81%,
      respectively and these values were significantly higher than that in 120 ppm.
      Incidences of lung metastasis in the 40 ppm group steadily increased up to 67% by
      week 36 while that in the 80 ppm increased sharply up to 86% by week 24. Severity
      of lung metastases in the 40 ppm group at week 36 was mild compared with the 80
      ppm group at week 24. In the second experiment, in order to characterize HCC
      development and lung metastasis in the 40 ppm group, rats given DEN and then
      followed with 40 ppm NMOR were killed sequentially. Development of HCC was
      observed at week 14 and reached 100% incidence at week 20. First lung metastatic
      lesions were evident at week 22, and incidence of lung metastasis reached 100%.
      Tumor cells were identified in the blood at week 20 by RT-PCR. The current study
      revealed that 40 ppm NMOR for 14 weeks after DEN treatment developed HCC without
      lung metastases at week 22, then HCC with a frequent lung metastasis at week 40.
      Thus, it can be said that this system is a more appropriate model for elucidation
      of mechanisms of metastasis and also for analysis of factors to inhibit natural
      metastasis.

PMID- 16283488
TI  - The proper role of bioethics.

PMID- 16283489
TI  - A new rejection of moral expertise.
AB  - There seem to be two clearly-defined camps in the debate over the problem of
      moral expertise. On the one hand are the "Professionals", who reject the
      possibility entirely, usually because of the intractable diversity of ethical
      beliefs. On the other hand are the "Ethicists", who criticise the Professionals
      for merely stipulating science as the most appropriate paradigm for discussions
      of expertise. While the subject matter and methodology of good ethical thinking
      is certainly different from that of good clinical thinking, they argue, this is
      no reason for rejecting the possibility of a distinctive kind of expertise in
      ethics, usually based on the idea of good justification. I want to argue that
      both are incorrect, partly because of the reasons given by one group against the
      other, but more importantly because both neglect what is most distinctive about
      ethics: that it is personal in a very specific way, without collapsing into
      relativism.

PMID- 16283490
TI  - In Defence of Ethicists. A Commentary on Christopher Cowley's Paper.

PMID- 16283491
TI  - Constructing critical bioethics by deconstructing culture/nature dualism.
AB  - This paper seeks to respond to some of the recent criticisms directed toward
      bioethics by offering a contribution to a "critical bioethics". Here this concept
      is principally defined in terms of the three features of interdisciplinarity,
      self-reflexivity and the avoidance of uncritical complicity. In a partial
      reclamation of the ideas of V.R. Potter, it is argued that a critical bioethics
      requires a meaningful challenge to culture/nature dualism, expressed in bioethics
      as the distinction between medical ethics and ecological ethics. Such a
      contesting of the "bio" in bioethics arrests its ethical bracketing of
      environmental and animal ethics. Taken together, the triadic definition of a
      critical bioethics offered here provides a potential framework with which to fend
      off critiques of commercial capture or of being "too close to science" commonly
      directed toward bioethics.

PMID- 16283492
TI  - Would they follow what has been laid down? Cancer patients' and healthy controls'
      views on adherence to advance directives compared to medical staff.
AB  - Advance directives are propagated as instruments to maintain patients' autonomy
      in case they can no longer decide for themselves. It has been never been examined
      whether patients' and healthy persons themselves are inclined to adhere to these
      documents. Patients' and healthy persons' views on whether instructions laid down
      in advance directives should be followed because that is (or is not) "the right
      thing to do", not because one is legally obliged to do so, were studied and
      compared with that of medical staff. METHOD: Vignette study presenting five
      cases. Cancer patients, healthy persons, nursing staff and physicians (n = 100 in
      each group) were interviewed. An adherence score was calculated (maximum value
      5). The adherence score is found to be low in all groups, yet lowest in patients
      (1.55; standard deviation 1.13) and healthy controls (1.60; 1.37). The scores are
      significantly different between nursing staff on the one hand and patients and
      healthy controls on the other (p < 0.005 and p < 0.05, respectively), and between
      doctors and patients (p < 0.05). Interviewees who want these documents to be
      followed tend to live alone and to have already written an advance directive.
      CONCLUSIONS: Cancer patients and healthy persons widely disregard instructions
      laid down in advance directives and consider them less binding than physicians
      and nursing staff do. Only a minority tends to adhere more to advance directives.
      To improve decision-making at the end of life when patients are no longer able to
      decide for themselves alternative concepts, such as advanced care planning,
      should be considered.

PMID- 16283493
TI  - Children, longitudinal studies, and informed consent.
AB  - This paper deals with ethical issues of particular relevance to longitudinal
      research involving children. First some general problems concerning information
      and lack of understanding are discussed. Thereafter focus is shifted to issues
      concerning information and consent procedures in studies that include young
      children growing up to become autonomous persons while the project still runs.
      Some of the questions raised are: When is it right to include children in
      longitudinal studies? Is an approval from the child needed? How should
      information to children be handled? A general point stressed is that autonomy
      considerations underline the importance of adjusting the information given to
      meet demands. A "presumption of competence" may be needed in research involving
      children, in order to pay their views sufficient attention.

PMID- 16283494
TI  - The right to withdraw consent to research on biobank samples.
AB  - Ethical guidelines commonly state that research subjects should have a right to
      withdraw consent to participate. According to the guidelines we have studied,
      this right applies also to research on biological samples. However, research
      conducted on human subjects themselves differs in important respects from
      research on biological samples. It is therefore not obvious that the same rights
      should be granted research participants in the two cases. This paper investigates
      arguments for and against granting a right to withdraw consent to research on
      biobank samples. We conclude that (1) there are no explicit arguments for such a
      right in the guidelines we have studied, (2) the arguments against such a right
      are inconclusive, (3) considerations of autonomy, privacy, personal integrity,
      and trust in medical research provide sufficient reasons for granting a right to
      withdraw consent to research on biobank samples, (4) in certain cases, research
      participants should be allowed to waive this right.

PMID- 16283495
TI  - The medical theory of Richard Koch II: natural philosophy and history.
AB  - Richard Koch(1) became known in the 1920s with works on basic medical theory.
      Among these publications, the character of medical action and its status within
      the theory of science was presented as the most important theme. While science is
      inherently driven by the pursuit of knowledge for its own sake, medicine pursues
      the practical purpose of helping the sick. Therefore, medicine must be seen as an
      active relationship between a helping and a suffering person. While elucidating
      this relationship, Koch discusses the fundamental elements of medicine found in
      natural philosophy and the relationship of medicine to its own history. One of
      his aims is to unite natural history and the history of ideas without reducing
      intellectual processes to biological ones. Koch considers free will as something
      intuitively certain. It must serve as an axiom which will capture human as well
      as non-human reality. Based on the fact that human free will, considered a
      psychic quality, evolved out of inanimate matter, Koch grants matter (proto-)
      psychic qualities. They are evoked through specific constellations of matter. -
      With regard to history, Koch rejects the notion of constant progress. The history
      of medicine has provided insights that cannot be surpassed but can be obscured.
      Historical self-contemplation serves as a means for avoiding any deviations which
      may prevent medicine from fulfilling its ultimate purpose. Koch connects nature
      and history through the concept of a unity between natural history and the
      historical development of medicine. Medicine is considered an especially complex
      development of a purposive reaction to harmful stimuli, a reaction which can
      already be encountered in unicellular organisms. Without intending to reduce
      historical and mental processes to biological ones, Koch sets for himself the aim
      of gathering different phenomena and presenting them in one encapsulating unity.

PMID- 16283496
TI  - Towards a dynamic definition of health and disease.
AB  - A multifactorial and growing crisis of health care systems in the developed world
      has affected medicine. In order to provide rational responses, some central
      concepts of the past, such as the definitions of health and disease, need to be
      updated. For this purpose physicians should initiate a new debate. As a point of
      departure the following definitions are proposed: Health is a dynamic state of
      wellbeing characterized by a physical, mental and social potential, which
      satisfies the demands of a life commensurate with age, culture, and personal
      responsibility. If the potential is insufficient to satisfy these demands the
      state is disease. This term includes sickness, illness, ill health, and malady.
      The described potential is divided into a biologically given and a personally
      acquired partial potential. Their proportions vary throughout the life cycle. The
      proposed definitions render it empirically possible to diagnose persons as
      healthy or diseased and to apportion some of the responsibility for their state
      of health to individuals themselves. Treatment strategies should always consider
      three therapeutic routes: improvements of the biologically given and of the
      personally acquired partial potentials and adaptations of the demands of life.
      These consequences favourably contrast with those resulting from the WHO
      definition of health.

PMID- 16283497
TI  - Why disease persists: an evolutionary nosology.
AB  - Although natural selection might be expected to reduce the incidence and severity
      of disease, disease persists. Natural selection leads to increases in the mean
      fitness of populations and so will reduce the frequency of disease-associated
      alleles, but other evolutionary processes, such as mutation and gene flow, may
      introduce or increase the frequency of these deleterious alleles. The pleiotropic
      actions of genes and the epistatic interactions between them complicate the
      relationship between genotype and phenotype, and may result in the preservation
      of disease-associated alleles. Deleterious alleles may also be maintained because
      of linkage to beneficial alleles. The inability of natural selection to eliminate
      diseases of aging is a reminder that fitness -- success in producing progeny, or
      in contributing genes to the population gene pool -- is not equivalent to the
      absence of disease. Nutritional or psychosocial cues may lead to life history
      strategies that maximize survival to reproductive maturity at the expense of
      disease later in life. Natural selection acts on genes, cells, and groups, as
      well as on organisms; the outcome of evolution reflects selection at different
      levels of biological organization. Finally, the human environment is constantly
      changing, largely because of the evolution of our parasites and because of
      changes in cultural beliefs and practices; genetic evolution is comparatively
      slow and lags behind environmental change. An evolutionary nosology complements
      traditional medical nosologies and enhances our understanding of the persistence
      of disease and the meaning of human variation.

PMID- 16283498
TI  - The confabulatory semiotics: naming and cognition of diseases by pathologists.

PMID- 16283499
TI  - The conflation of competence and capacity in english medical law: a philosophical
      critique.
AB  - Ethical and legal discourse pertaining to the ability to consent to treatment and
      research in England operates within a dualist framework of "competence" and
      "capacity". This is confusing, as while there exists in England two possible
      senses of legal capacity -- "first person" legal capacity and "delegable" legal
      capacity, currently neither is formulated to bear a necessary relationship with
      decision-making competence. Notwithstanding this, judges and academic
      commentators frequently invoke competence to consent in discussions involving the
      validity of offering or withholding consent as a synonym for legal capacity to
      consent. I argue that this gives rise to a conflation, jeopardising clarity and
      consistency in law. This is somewhat less problematic in instances of "first
      person" legal capacity that are heavily informed by criteria for decision-making
      competence than in the second sense of legal capacity, which is qualitatively
      different from decision-making competence, or with first-person legal capacity
      when defined in different terms from competence. The paper concludes by proposing
      that the soundest resolution to this problem is by making decision-making
      competence a necessary and sufficient condition of first-person legal capacity,
      affording a more scrupulous distinction between the two different forms of legal
      capacity that exist.

PMID- 16283500
TI  - Master programme "health, human rights and ethics": a curriculum development
      experience at Andrija Stampar School of Public Health, Medical School, University
      of Zagreb.

PMID- 16283501
TI  - Overcritical, overfriendly? A dialogue between a sociologist and a philosopher on
      genetic technology and its applications.

PMID- 16283509
TI  - Proceedings of the 3rd International Conference on Molecular Mechanisms of Metal
      Toxicity and Carcinogenesis, September 11-15, 2004, Morgantown, West Virginia,
      USA.

PMID- 16283511
TI  - Effect of stainless steel manual metal arc welding fume on free radical
      production, DNA damage, and apoptosis induction.
AB  - Questions exist concerning the potential carcinogenic effects after welding fume
      exposure. Welding processes that use stainless steel (SS) materials can produce
      fumes that may contain metals (e.g., Cr, Ni) known to be carcinogenic to humans.
      The objective was to determine the effect of in vitro and in vivo welding fume
      treatment on free radical generation, DNA damage, cytotoxicity and apoptosis
      induction, all factors possibly involved with the pathogenesis of lung cancer. SS
      welding fume was collected during manual metal arc welding (MMA). Elemental
      analysis indicated that the MMA-SS sample was highly soluble in water, and a
      majority (87%) of the soluble metal was Cr. Using electron spin resonance (ESR),
      the SS welding fume had the ability to produce the biologically reactive hydroxyl
      radical (*OH), likely as a result of the reduction of Cr(VI) to Cr(V). In vitro
      treatment with the MMA-SS sample caused a concentration-dependent increase in DNA
      damage and lung macrophage death. In addition, a time-dependent increase in the
      number of apoptotic cells in lung tissue was observed after in vivo treatment
      with the welding fume. In summary, a soluble MMA-SS welding fume was found to
      generate reactive oxygen species and cause DNA damage, lung macrophage
      cytotoxicity and in vivo lung cell apoptosis. These responses have been shown to
      be involved in various toxicological and carcinogenic processes. The effects
      observed appear to be related to the soluble component of the MMA-SS sample that
      is predominately Cr. A more comprehensive in vivo animal study is ongoing in the
      laboratory that is continuing these experiments to try to elucidate the potential
      mechanisms that may be involved with welding fume-induced lung disease.

PMID- 16283510
TI  - Conference overview: molecular mechanisms of metal toxicity and carcinogenesis.
AB  - Chronic exposure to many heavy metals and metal-derivatives is associated with an
      increased risk of cancer, although the mechanisms of tumorigenesis are largely
      unknown. Approximately 125 scientists attended the 3rd Conference on Molecular
      Mechanisms of Metal Toxicity and Carcinogenesis and presented the latest research
      concerning these mechanisms. Major areas of focus included exposure assessment
      and biomarker identification, roles of ROS and antioxidants in carcinogenesis,
      mechanisms of metal-induced DNA damage, metal signalling, and the development of
      animal models for use in metal toxicology studies. Here we highlight some of the
      research presented, and summarize the conference proceedings.

PMID- 16283512
TI  - ERKs activation and calcium signaling are both required for VEGF induction by
      vanadium in mouse epidermal Cl41 cells.
AB  - The previous studies have demonstrated that vanadium exposure can cause a variety
      of biological effects. However, the mechanisms involved in the biological effects
      caused by vanadium are not well understood. Our previous studies have shown that
      exposure of mouse epidermal Cl 41 cells to vanadate stimulated the
      phosphorylation of both ERKs and p38K, and calcium signaling leading NFAT
      activation. In view of the evidence that ERKs and p38 kinase contribute to VEGF
      induction, we investigated in the present study the potential roles of ERKs,
      p38K, and calcium signaling in VEGF induction caused by vanadium exposure.
      Exposure of Cl 41 cells to vanadium led to VEGF induction in both time- and dose
      dependent manners. Pre-treatment of Cl 41 cells with PD98059, an inhibitor of
      MEK1/2-ERKs pathway, but not SB202190, an inhibitor for p38K pathway, resulted in
      a dramatic inhibition of VEGF induction by vanadium. More interesting, pre
      treatment of Cl 41 cells with intracellular calcium chelator, but not calcium
      channel blocker, resulted in a dramatic decrease in VEGF induction by vanadium.
      However, both PI-3K inhibitors and overexpression of Deltap85, a dominant
      negative PI-3K mutant, resulted in only a marginal decrease in VEGF induction by
      vanadium. Moreover, mTOR, as a downstream molecule of PI-3K, did not attribute to
      VEGF induction by vanadium because rapamycin pre-treatment did not show any
      inhibitory effect on VEGF induction. These results indicate that ERKs and
      intracellular stored calcium release play a critical role in VEGF induction by
      vanadium. PI-3K is partially involved in VEGF induction by vanadium, while p38K
      and mTOR are not involved. Those results will help us to understand the molecular
      mechanisms involved in vanadium-induced biological effects.

PMID- 16283513
TI  - Essential role of PI-3K, ERKs and calcium signal pathways in nickel-induced VEGF
      expression.
AB  - Exposure to a highly nickel-polluted environment has the potential to cause a
      variety of adverse health effects, such as the respiratory tract cancers. Since
      numerous studies have demonstrated that nickel generally has weak mutagenic
      activity, research focus had turned to cell signalling activation leading to gene
      modulation and epigenetic changes as a plausible mechanism of carcinogenesis.
      Previous studies have revealed that nickel compounds can induce the expression of
      vascular endothelial growth factor (VEGF), which is a key mediator of
      angiogenesis both in physiological and pathologic conditions. In the present
      study, we investigated the potential roles of PI-3K, ERKs, p38 kinase and calcium
      signalling in VEGF induction by nickel in Cl 41 cells. Exposure of Cl 41 cells to
      nickel compounds led to VEGF induction in both time- and dose-dependent manners.
      Pre-treatment of Cl 41 cells with PI-3K inhibitor, wortmannin or Ly294002,
      resulted in a striking inhibition of VEGF induction by nickel compounds,
      implicating the role of PI-3K in the induction. However, mTOR, one of downstream
      molecules of PI-3K, may not contribute to the induction because pre-treatment of
      Cl 41 cells with its inhibitor, rapamycin, did not show obvious decrease in
      nickel-induced VEGF expression. Furthermore, pre-treatment of Cl 41 cells with
      MEK1/2-ERKs pathway inhibitor, PD98059, significantly inhibited VEGF induction by
      both NiCl2 and Ni3S2, whereas p38 kinase inhibitor, SB202190, did not impair the
      induction. Pre-treatment of Cl 41 cells with intracellular calcium chelator, but
      not calcium channel blocker, inhibited VEGF induction by nickel. Collectively
      these data demonstrate that PI-3K, ERKs and cytosolic calcium, but not p38
      kinase, play essential roles in VEGF induction by nickel compounds.

PMID- 16283515
TI  - Involvement of the p38 MAP kinase in Cr(VI)-induced growth arrest and apoptosis.
AB  - Hexavalent chromium [Cr(VI)] is a carcinogenic genotoxin commonly found in
      industry and the environment. DNA damage resulting from Cr(VI) exposure triggers
      numerous stress responses, including activation of cell cycle checkpoints and
      initiation of apoptosis. Mechanisms controlling these responses, while
      extensively studied, have yet to be fully elucidated. Here, we demonstrate that
      the p38 mitogen-activated protein kinase (MAPK) is activated by Cr(VI) exposure
      and that inhibition of p38 function using the selective inhibitor SB203580
      results in abrogation of S-phase and G2 cell cycle checkpoints in response to
      Cr(VI). Also, we observe that inhibition of p38 results in decreased cell
      survival and increased percentage of apoptotic cells following Cr(VI) treatment.
      Taken together, these results indicate that p38 function is critical for optimal
      stress response induced by Cr(VI) exposure.

PMID- 16283516
TI  - Human lung cell growth is not stimulated by lead ions after lead chromate-induced
      genotoxicity.
AB  - Chromate compounds are known human lung carcinogens. Water solubility is an
      important factor in the carcinogenicity of these compounds with the most potent
      carcinogenic compounds being water-insoluble or 'particulate'. Previously we have
      shown that particulate chromates dissolve extracellularly releasing chromium (Cr)
      and lead (Pb) ions and only the Cr ions induce genotoxicity. Pb ions have been
      considered to have epigenetic effects and it is thought that these may enhance
      the carcinogenic activity of lead chromate, perhaps by stimulating Cr-damaged
      cells to divide. However, this possibility has not been directly tested.
      Accordingly, we investigated the ability of Pb ions to stimulate human lung cells
      and possibly force lead chromate-damaged cells to grow. We found that at
      concentrations of lead chromate that induced damage, human lung cells exhibited
      cell cycle arrest and growth inhibition that were very similar to those observed
      for sodium chromate. Moreover, we found that soluble Pb ions were not growth
      stimulatory to human lung cells and in fact induced progressive mitotic arrest.
      These data indicate that lead chromate-generated Cr ions cause growth inhibition
      and cell cycle arrest and that Pb does not induce epigenetic effects that
      stimulate chromate-damaged cells to grow.

PMID- 16283514
TI  - Carcinogenic effect of nickel compounds.
AB  - Nickel is a widely distributed metal that is industrially applied in many forms.
      Accumulated epidemiological evidence confirms that exposures to nickel compounds
      are associated with increased nasal and lung cancer incidence, both in mostly
      occupational exposures. Although the molecular mechanisms by which nickel
      compounds cause cancer are still under intense investigation, the carcinogenic
      actions of nickel compounds are thought to involve oxidative stress, genomic DNA
      damage, epigenetic effects, and the regulation of gene expression by activation
      of certain transcription factors related to corresponding signal transduction
      pathways. The present review summarizes our current knowledge on the molecular
      mechanisms of nickel carcinogenesis, with special emphasis on the role of nickel
      induced reactive oxygen species (ROS) and signal transduction pathways.

PMID- 16283517
TI  - Nucleotide excision repair functions in the removal of chromium-induced DNA
      damage in mammalian cells.
AB  - Some hexavalent chromium (Cr(VI))-containing compounds are human lung
      carcinogens. While ample information is available on the genetic lesions produced
      by Cr, surprisingly little is known regarding the cellular mechanisms involved in
      the removal of Cr-DNA adducts. Nucleotide excision repair (NER) is a highly
      versatile pathway that is responsive to a variety of DNA helix-distorting
      lesions. Binary Cr-DNA monoadducts do not produce a significant degree of helical
      distortion. However, these lesions are unstable due to the propensity of Cr(III)
      to form DNA adducts (DNA interstrand crosslinks, DNA-protein/amino acid ternary
      adducts) which may serve as substrates for NER. Therefore, the focus of this
      study was to determine the role of NER in the processing of Cr-DNA damage using
      normal (CHO-AA8) and NER-deficient [UV-5 (XP-D); UV-41 (ERCC4/XP-F)] hamster
      cells. We found that both UV-5 and UV-41 cells exhibited an increased sensitivity
      towards Cr(VI)-induced clonogenic lethality relative to AA8 cells and were
      completely deficient in the removal of Cr-DNA adducts. In contrast, repair
      complemented UV-5 (expressing hamster XPD) and UV-41 (expressing human ERCC4)
      cells exhibited similar clonogenic survival and removed Cr-DNA adducts to a
      similar extent as AA8 cells. In order to extend these findings to the molecular
      level, we examined the ability of Cr(III)-damaged DNA to induce DNA repair
      synthesis in cell extracts. Repair synthesis was observed in reactions using
      extracts derived from AA8, or repair-complemented, but not NER-deficient cells.
      Cr(III)-induced repair resynthesis was sensitive to inhibition by the DNA
      polymerase delta/epsilon inhibitor, aphidicolin, but not 2',3'-dideoxythymidine
      triphosphate (ddTTP), a polymerase beta inhibitor. These results collectively
      suggest that NER functions in the protection of cells from Cr(VI) lethality and
      is essential for the removal of Cr(III)-DNA adducts. Consequently, NER may
      represent an important mechanism for preventing Cr(VI)-induced mutagenesis and
      neoplastic transformation.

PMID- 16283518
TI  - Leukemic transformation of hematopoietic cells in mice internally exposed to
      depleted uranium.
AB  - Depleted uranium (DU) is a dense heavy metal used in military applications.
      During military conflicts, US military personnel have been wounded by DU
      shrapnel. The health effects of embedded DU are unknown. Published data from our
      laboratory demonstrated that DU exposure in vitro can transform immortalized
      human osteoblast cells (HOS) to the tumorigenic phenotype. Results from our
      laboratory have also shown that DU is genotoxic and mutagenic in cultured human
      cells. Internalized DU could be a carcinogenic risk and concurrent alpha particle
      and heavy metal toxic effects complicate this potential risk. Anecdotal reports
      have suggested that DU can cause leukemia. To better assess this risk, we have
      developed an in vivo leukemogenesis model. This model involves using murine
      hematopoietic cells (FDC-P1) that are dependent on stimulation by granulocyte
      macrophage colony stimulating factor (GM-CSF) or interleukin 3 (IL-3) and
      injected into mice to produce myeloid leukemia. Although immortalized, these
      cells are not tumorigenic on subcutaneous inoculation in mice. Intravenous
      injection of FDC-P1 cells into DU-implanted DBA/2 mice was followed by the
      development of leukemias in 76% of all mice implanted with DU pellets. In
      contrast, only 12% of control mice developed leukemia. Karyotypic analysis
      confirmed that the leukemias originated from FDC-P1 cells. The growth properties
      of leukemic cells from bone marrow, spleen, and lymph node were assessed and
      indicate that the FDC-P1 cells had become transformed in vivo. The kidney,
      spleen, bone marrow, muscle, and urine showed significant elevations in tissue
      uranium levels prior to induction of leukemia. These results demonstrated that a
      DU altered in vivo environment may be involved in the pathogenesis of DU induced
      leukemia in an animal model.

PMID- 16283519
TI  - Inorganic arsenic compounds cause oxidative damage to DNA and protein by inducing
      ROS and RNS generation in human keratinocytes.
AB  - Arsenic is a naturally occurring element that is present in food, soil, and
      water. Inorganic arsenic can accumulate in human skin and is associated with
      increased risk of skin cancer. Oxidative stress due to arsenic exposure is
      proposed as one potential mode of carcinogenic action. The purpose of this study
      is to investigate the specific reactive oxygen and nitrogen species that are
      responsible for the arsenic-induced oxidative damage to DNA and protein. Our
      results demonstrated that exposure of human keratinocytes to trivalent arsenite
      caused the generation of 8-hydroxyl-2'-deoxyguanine (8-OHdG) and 3-nitrotyrosine
      (3-NT) in a concentration- and time-dependent manner. Pentavalent arsenate had
      similar effects, but to a significantly less extent. The observed oxidative
      damage can be suppressed by pre-treating cells with specific antioxidants.
      Furthermore, we found that pre-treating cells with Nomega-nitro-L-arginine methyl
      ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), or with 5,10,15,20
      tetrakis (N-methyl-4'-pyridyl) porphinato iron (III) chloride (FeTMPyP), a
      decomposition catalyst of peroxynitrite, suppressed the generation of both 8-OHdG
      and 3-NT, which indicated that peroxynitrite, a product of the reaction of nitric
      oxide and superoxide, played an important role in arsenic-induced oxidative
      damage to both DNA and protein. These findings highlight the involvement of
      peroxynitrite in the molecular mechanism underlying arsenic-induced human skin
      carcinogenesis.

PMID- 16283520
TI  - Oxidation and methylation status determine the effects of arsenic on the mitotic
      apparatus.
AB  - We investigated the spindle inhibitory properties of six arsenicals differing in
      their methylation or oxidation state. Human lymphoblasts were exposed for 6 h to
      either sodium arsenate (NaAs(V)), sodium arsenite (NaAs(III)), monomethylarsonic
      acid (MMA(V)), monomethylarsonous acid (MMA(III)), dimethylarsinic acid (DMA(V)),
      or dimethylarsinous acid (DMA(III)). After exposure slides were prepared, and the
      mitotic indices (MI) were assessed. We also exposed tubulin directly to each
      arsenical and spectrophotometrically measured its effect on polymerization.
      NaAs(V) caused a small but significant increase in MI. MMA(V) also caused only a
      slight increase in MI that just reached statistical significance. In contrast,
      DMA(V) caused a significant increase in MI, producing approximately 75% the MI of
      demecolcine and approximately 4 times the MI of the control. NaAs(III) had no
      significant effect on MI and was quite toxic. MMA(III) induced more than a
      twofold increase in MI compared to the control, which was about 40% that caused
      by demecolcine. On a micromolar basis, MMA(III) was the most potent of the
      arsenicals tested. DMA(III) gave inconsistent results. None of the pentavalent
      arsenicals had a substantial effect (either inhibition or enhancement) on GTP
      induced polymerization of tubulin. In contrast, NaAs(III) inhibited
      polymerization at concentrations of 1 mM and above and MMA(III) and DMA(III) at
      10 microM and above. Taken together, these results present a complex picture of
      how arsenicals may affect cells. These studies demonstrate that the metabolites
      of arsenic are active not only as chromosome breaking and DNA damaging agents but
      can also interfere with cell division via tubulin disruption.

PMID- 16283521
TI  - Sodium arsenite-induced inhibition of eukaryotic translation initiation factor 4E
      (eIF4E) results in cytotoxicity and cell death.
AB  - Exposure to arsenic (As) is a risk factor for the development of diabetes,
      vascular diseases and cancer. Several theories have been proposed to account for
      the mechanisms potentially responsible for As toxicity and carcinogenesis.
      Currently, we have investigated whether the eukaryotic translation initiation
      factor 4E (eIF4E), the mRNA cap binding and rate limiting factor required for
      translation, is a target for As-induced cytotoxicity and cell death. We have also
      investigated the potential cellular mechanisms underlying the As-induced de
      regulation of expression of eIF4E that are most likely responsible for the
      cytotoxicity and cell death induced by As. Exposure of four different human cell
      lines - HCT15 (colorectal adenocarcinoma), PLC/PR/5 (hepatocellular carcinoma),
      HeLa (cervical adenocarcinoma) and Chang (likely derived from HeLa cells) to
      sodium arsenite (NaAsO2) for time intervals up to 24 h resulted in a
      concentration-dependent cytotoxicity and cell death. All the NaAsO2-treated cells
      exhibited significant inhibition of eIF4E gene (protein). The potential
      involvement of eIF4E gene expression in the NaAsO2-induced cytotoxicity and cell
      death was investigated by silencing the cellular expression of the eIF4E gene by
      employing a small interfering RNA (SiRNA) specifically targeting the eIF4E gene's
      expression. The SiRNA-mediated silencing of eIF4E gene expression also resulted
      in significant cytotoxicity and cell death suggesting that the toxicity noticed
      among the NaAsO2-treated cells was probably due to the chemically induced
      inhibition of eIF4E gene expression. The potential involvement of inhibition of
      eIF4E gene expression in the NaAsO2-induced cytotoxicity and cell death was
      further investigated by employing transgenic cell lines overexpressing the eIF4E
      gene. Overexpression of the eIF4E gene in the Chinese hamster ovary cell line was
      protective against the NaAsO2-induced cytotoxicity and cell death. Additional
      studies conducted to understand the potential mechanisms responsible for NaAsO2
      induced inhibition of eIF4E gene expression demonstrated that exposure to NaAsO2
      resulted in transcriptional down-regulation of the eIF4E gene only in HCT-15 and
      HeLa cells, while in the NaAsO2-treated and PLC/PR/5 and Chang cells, the eIF4E
      mRNA expression level was comparable to those of the corresponding control cells.
      Cellular levels of ubiquitin and the process of ubiquitination were significantly
      higher in the NaAsO2-treated cells compared with the control cells.
      Immunoprecipitation of lysates obtained from the NaAsO2-treated cells and the
      subsequent western blot analysis of the immunoprecipitated protein(s) using the
      eIF4E antibody detected the presence of eIF4E protein in the immunoprecipitate
      suggesting possible ubiquitination of eIF4E protein in the NaAsO2-treated cells.
      Pre-exposure of the NaAsO2-treated cells to proteasome inhibitors blocked the
      inhibition of eIF4E gene expression as well as the resulting cytotoxicity and
      cell death. Furthermore, exposure of cells to NaAsO2 resulted in a significant
      inhibition of expression of the cell cycle and growth regulating gene, cyclin D1.
      Whether or not the inhibition of cyclin D1 in the NaAsO2-treated cells is
      mediated through the inhibition of eIF4E was tested by silencing the expression
      of eIF4E gene in the cells. Transfection of cells with SiRNA specifically
      targeting eIF4E gene expression resulted in a significant inhibition of cyclin D1
      gene suggesting that the observed inhibition of cyclin D1 gene in the NaAsO2
      treated cells is most likely mediated through inhibition of eIF4E gene. Taken
      together, our results indicate that the exposure of cells to NaAsO2 resulted in
      cytotoxicity and cell death, at least in part, due to the inhibition of eIF4E
      gene expression leading to diminished cellular levels of critical genes such as
      cyclin D1.

PMID- 16283522
TI  - Inhibition of core histones acetylation by carcinogenic nickel(II).
AB  - Nickel, a well-established human carcinogen, was shown to decrease acetylation of
      histones H4 and H3 in cultured cells. Such a decrease is expected to suppress
      gene expression. However, nickel is known to not only suppress but also enhance
      the expression of many genes. So, perhaps, nickel can alter histone acetylation
      in a more complex way? In a first step of testing this presumption, we examined
      acetylation status of histones H2A, H2B, H3 and H4, in human (HAE) and rat (NRK)
      cells exposed to nickel(II) under various conditions. In both cell lines,
      acetylation of all four histones was down-regulated by nickel(II) in a
      concentration- and time-dependent manner. Acetylation of histone H2B was
      suppressed to greater extent than that of the others, with histone H3 being
      relatively least affected. The analysis of acetylation status of each of the four
      lysine sites at the N-terminal tail of histone H2B revealed decreases consistent
      with those observed in the total acetylation patterns, with the K12 and K20
      residues being markedly more affected than K5 and K15 residues. Thus, the
      decrease in acetylation was to some degree site specific. In NRK cells, the
      observed uniform down-regulation of histone acetylation was consistent with a
      marked suppression of global gene transcription measured as [3H]-uridine
      incorporation into mRNA. However, in HAE cells, global RNA expression was
      transiently increased (in 24 h) before dropping below control after longer
      exposure (3 days). In conclusion, the effects of Ni(II) on histone acetylation
      are inhibitory, with their extent depending on the dose and exposure time. This
      uniform inhibition, however, is not consistently reflected in global RNA
      expression that in HAE cells may include both increase and decrease of the
      expression, clearly indicating the involvement of factors other than histone
      acetylation. The observed effects may contribute to neoplastic transformation of
      Ni(II)-exposed cells.

PMID- 16283523
TI  - Expression of copper-responsive genes in HepG2 cells.
AB  - The hypothesis that copper modulates the activity of intracellular signal
      transduction pathways to affect transcription, which ultimately disrupts normal
      development was investigated. Preliminary analysis of transcriptomes from HepG2
      cells exposed to copper for 4 and 24 h identified 19 and 7 up-regulated genes
      (twofold; p <or= 0.05), respectively. Among the up-regulated genes, several have
      been previously reported to be responsive to metals or oxidative stress.
      Differentially expressed genes were grouped by the functional categories based on
      gene ontology (GO). Significantly enriched GO categories (p < 0.01) included
      copper ion homeostasis, cadmium and copper ion binding, and heme oxygenase and
      oxidoreductase activities. Real-time RT-PCR confirmed the effect of copper on the
      levels of MT2A, HSPA1A, CYP1A1 and HMOX1 expression.

PMID- 16283524
TI  - Differential impact of ionic and coordinate covalent chromium (Cr)-DNA binding on
      DNA replication.
AB  - The reactive species produced by the reduction of Cr(VI), particularly Cr(III),
      can form both ionic and coordinate covalent complexes with DNA. These Cr(III)-DNA
      interactions consist of Cr-DNA monoadducts, Cr-DNA ternary adducts, and Cr-DNA
      interstrand cross-links (Cr-ICLs), the latter of which are DNA polymerase
      arresting lesions (PALs). We sought to determine the impact of Cr-DNA
      interactions on the formation of replication blocking lesions in S. cerevisiae
      using a PCR-based method. We found that target sequence (TS) amplification using
      DNA isolated from Cr(VI)-treated yeast actually increased as a function of Cr(VI)
      concentration. Moreover, the enhanced TS amplification was reproduced in vitro
      using Cr(III)-treated DNA. In contrast, PCR amplification of TS from DNA isolated
      from yeast exposed to equitoxic doses of the inorganic DNA cross-linking agent
      cisplatin (CDDP), was decreased in a concentration-dependent manner. This paradox
      suggested that a specific Cr-DNA interaction, such as an ionic Cr-DNA complex,
      was responsible for the enhanced TS amplification, thereby masking the
      replication-blocking effect of certain ternary Cr-DNA adducts (i.e. interstrand
      cross-links). To test this possibility, we removed ionically associated Cr from
      the DNA using salt extraction prior to PCR analysis. This procedure obviated the
      increased amplification and revealed a dose-dependent decrease in TS
      amplification and an increase in Cr-PALs. These data from DNA analyzed ex vivo
      after treatment of intact cells indicate that ionic interactions of Cr with DNA
      result in increased DNA amplification whereas coordinate-covalent Cr-DNA
      complexes lead to formation of Cr-PALs. Thus, these results suggest that
      treatment of living cells with Cr(VI) leads to two modes of Cr-binding, which may
      have conflicting effects on DNA replication.

PMID- 16283525
TI  - Soluble nickel interferes with cellular iron homeostasis.
AB  - Soluble nickel compounds are likely human carcinogens. The mechanism by which
      soluble nickel may contribute to carcinogenesis is unclear, though several
      hypotheses have been proposed. Here we verify the ability of nickel to enter the
      cell via the divalent metal ion transporter 1 (DMT1) and disturb cellular iron
      homeostasis. Nickel may interfere with iron at both an extracellular level, by
      preventing iron from being transported into the cell, and at an intracellular
      level, by competing for iron sites on enzymes like the prolyl hydroxylases that
      modify hypoxia inducible factor-1alpha (HIF-1alpha). Nickel was able to decrease
      the binding of the Von Hippel-Lindau (VHL) protein to HIF-1alpha, indicating a
      decrease in prolyl hydroxylase activity. The ability of nickel to affect various
      iron dependent processes may be an important step in nickel dependent
      carcinogenesis. In addition, understanding the mechanisms by which nickel
      activates the HIF-1alpha pathway may lead to new molecular targets in fighting
      cancer.

PMID- 16283526
TI  - Deficiency in Ikkbeta gene enhances arsenic-induced gadd45alpha expression.
AB  - Chronic arsenic exposure is implicated in the pathophysiology of various human
      diseases, including cancer and diabetes. Using Ikkbeta gene knockout mouse
      embryonic fibroblast cells (Ikkbeta-/-), in the present study we demonstrated
      that NF-kappaB inhibition due to Ikkbeta deficiency up-regulated basal and
      arsenic-induced expression of gadd45alpha. In addition to gadd45alpha, the basal
      expression of other gadd family members including gadd45beta, gadd45gamma and
      gadd153 was substantially increased in Ikkbeta-/- cells. Ikkbeta deficiency
      prevented the induction of gadd45beta and gadd45gamma by arsenic, whereas the
      induction of gadd45alpha and gadd153 was appreciably enhanced in Ikkbeta-/-
      cells. Furthermore, a substantial decrease in the expression of c-myc, an
      established endogenous transcriptional repressor of gadd45alpha and gadd153
      genes, was noted. Thus, these results uncover the molecular mechanism by which NF
      kappaB signalling contributes to the regulation of gadd family gene expression
      induced by arsenic.

PMID- 16283527
TI  - Resistance to apoptosis, increased growth potential, and altered gene expression
      in cells that survived genotoxic hexavalent chromium [Cr(VI)] exposure.
AB  - Certain hexavalent chromium [Cr(VI)] compounds are known genotoxic respiratory
      carcinogens, which induce apoptosis as a predominant mode of cell death.
      Selection of cells that are resistant to apoptosis may be a factor in tumour
      progression. We developed sub-populations of telomerase-transfected human
      fibroblasts (BJ-hTERT) that survived a 99% clonogenically lethal exposure to
      Cr(VI) (B-5Cr). B-5Cr cells were markedly resistant to apoptosis induced by
      several agents and exhibited increased clonogenic survival, especially at
      apoptogenic doses. B-5Cr cells did not exhibit altered cellular uptake of Cr(VI)
      and retained a normal p53 response to Cr(VI) exposure. We conducted large-scale
      gene expression analysis at different time-points after a secondary genotoxic
      Cr(VI) insult in B-5Cr and BJ-hTERT cells using Affymetrix Genechip human genome
      arrays. Cr(VI) exposure led to differential regulation of many genes, which
      affect a diverse set of cellular activities such as transcription, signal
      transduction, stress response, cell adhesion, DNA repair, apoptosis and cell
      cycle modulation. We compared Cr(VI)-induced altered gene expression in the B-5Cr
      cells to that in the parental cells and identified 223, 147 and 204 genes with at
      least a two-fold difference in expression at 4, 8 and 18 h after exposure,
      respectively. Cluster analysis by gene function revealed altered expression of
      genes involved in apoptosis, cell cycle regulation and DNA repair. Our data
      suggest an alteration in gene expression that may favor cell survival and/or
      incomplete DNA repair after genotoxic exposure. Selection of cells with altered
      expression of these genes may constitute the early stages of tumour progression.

PMID- 16283530
TI  - Fluorescent properties of pentamethine cyanine dyes with cyclopentene and
      cyclohexene group in presence of biological molecules.
AB  - A series of pentamethine cyanine dyes with cyclohexene or cyclopentene group in
      polymethyne chain, assumed as DNA groove-binders, were studied as fluorescent
      probes for nucleic acids as well as for native and denatured proteins. It was
      revealed that the presence of methyl or dimethyl substituent in 5 position of the
      cyclohexene group hinders the formation of dye-DNA fluorescent complex, while the
      methyl substituent in 2 position leads to the increasing of the dye-DNA complex
      fluorescence intensity. The dyes SL-251, SL-1041, and SL-1046 containing methyl
      group in the 2 position of the cyclic group, are reported as bright DNA-sensitive
      dyes. The study of the dyes DNA-binding specificity demonstrated significant AT
      preference that points to the groove-binding interaction mode. At the same time,
      the dyes SL-251, SL-377, and SL-957 with the 2-methyl substituted cyclohexene
      group were shown to be sensitive fluorescent dyes both for nonspecific (in SDS
      presence) proteins detection and for native BSA.

PMID- 16283531
TI  - "Entre dos mundos" (Between Two Worlds): bicultural skills training with Latino
      immigrant families.
AB  - This paper focuses on the acculturation model of second-culture-acquisition for
      Latino immigrants. Two theoretical frameworks, assimilation and alternation
      theories, are compared within the acculturation model. Empirical research
      findings suggest that assimilation is a risk factor for increases in negative
      health behaviors and mental health problems. Conversely, biculturalism appears to
      be an emerging protective factor that buffers assimilation stress, enhances socio
      cognitive functioning, and increases academic achievement. A review of bicultural
      skills training interventions shows these programs are effective in decreasing
      the risk for problematic behavior. Finally, a refined model of bicultural skills
      training for Latino immigrant families is proposed based on the acculturation
      research literature and extensive interviews with Latino families in North
      Carolina.

PMID- 16283532
TI  - Factors associated with intention to breastfeed among low-income, inner-city
      pregnant women.
AB  - OBJECTIVES: To examine the relationship between sociodemographic factors,
      maternal characteristics, and intention to breastfeed among low-income, inner
      city pregnant women. METHODS: English and Spanish speaking low-income women
      recruited from local Philadelphia health centers were surveyed at the time of
      their first prenatal care visit. At the time of the visit, respondents were asked
      whether or not they planned to breastfeed their infant. The responses of 2,690
      women were included in these analyses. Multivariate logistic regression was used
      to assess the independent associations of race/ethnicity, nativity status,
      education, and other factors on the odds of intending to breastfeed. RESULTS:
      About half (53%) of the respondents reported that they intended to breastfeed
      their infant. In adjusted logistic regression models, immigrant black (adjusted
      OR [aOR] 5.82; 95% confidence interval [CI] 3.86, 8.77), other Hispanic (who were
      predominantly foreign-born) (aOR 6.05; 95% CI 3.92, 9.33), and island-born Puerto
      Rican (aOR 3.48; 95% CI 2.04, 5.95) women were significantly more likely to
      report that they intended to breastfeed than non-Hispanic whites. Somewhat
      surprisingly, non-Hispanic, US-born African Americans in this low-income sample
      were more likely to report that they intended to breastfeed than non-Hispanic
      white respondents (aOR 1.59; 95% CI 1.20, 2.11). Lower education, not living with
      the baby's father, multiparous pregnancy, and smoking were negatively and
      independently associated with intention to breastfeed. Maternal age, household
      income, public housing, and depressive symptoms were not significant predictors
      of breastfeeding intention in adjusted multivariate models. CONCLUSIONS:
      Significant differences were documented in breastfeeding intention in our sample
      of low-income, inner-city women. Most notable was the higher likelihood of
      anticipated breastfeeding among our immigrant sub-groups when compared with non
      Hispanic white women. An unexpected finding was the higher likelihood of
      anticipated breastfeeding among native-born, non-Hispanic African American women
      than among non-Hispanic white respondents. Because intentions are important
      predictors of future behavior, more focus needs to be directed towards
      breastfeeding promotion during the prenatal period and towards a better
      understanding of why some mothers intend to breastfeed while others do not.

PMID- 16283533
TI  - Conditioning on certain random events associated with statistical variability in
      PK/PD.
AB  - In PK/PD data analysis, statistical models involving random variables are
      developed. At times an analysis can be carried out by conditioning on certain
      random events involving these variables. This paper attempts to clarify issues
      regarding conditioning. In particular, conditioning is examined as it relates to
      a number of disparate practical matters: missing covariate values, dose
      titration, BQL data, "no change from baseline" data, and the use of a truncated
      intraindividual probability distribution for PK observations.

PMID- 16283534
TI  - How modeling and simulation have enhanced decision making in new drug
      development.
AB  - The idea of model-based drug development championed by Lewis Sheiner, in which
      pharmacostatistical models of drug efficacy and safety are developed from
      preclinical and available clinical data, offers a quantitative approach to
      improving drug development and development decision-making. Examples are
      presented that support this paradigm. The first example describes a preclinical
      model of behavioral activity to predict potency and time-course of response in
      humans and assess the potential for differentiation between compounds. This
      example illustrates how modeling procedures expounded by Lewis Sheiner provided
      the means to differentiate potency and the lag time between drug exposure and
      response and allow for rapid decision making and dose selection. The second
      example involves planning a Phase 2a dose-ranging and proof of concept trial in
      Alzheimer's disease (AD). The issue was how to proceed with the study and what
      criteria to use for a go/no go decision. The combined knowledge of AD disease
      progression, and preclinical and clinical information about the drug were used to
      simulate various clinical trial scenarios to identify an efficient and effective
      Phase 2 study. A design was selected and carried out resulting in a number of
      important learning experiences as well as extensive financial savings. The
      motivation for this case in point was the "Learn-Confirm" paradigm described by
      Lewis Sheiner. The final example describes the use of Pharmacokinetic and
      Pharmacodynamic (PK/PD) modeling and simulation to confirm efficacy across doses.
      In the New Drug Application for gabapentin, data from two adequate and well
      controlled clinical trials was submitted to the Food and Drug Administration
      (FDA) in support of the approval of the indication for the treatment of post
      herpetic neuralgia. The clinical trial data was not replicated for each of the
      sought dose levels in the drug application presenting a regulatory dilemma.
      Exposure response analysis submitted in the New Drug Application was applied to
      confirm the evidence of efficacy across these dose levels. Modeling and
      simulation analyses showed that the two studies corroborate each other with
      respect to the pain relief profiles. The use of PK/PD information confirmed
      evidence of efficacy across the three studied doses, eliminating the need for
      additional clinical trials and thus supporting the approval of the product. It
      can be speculated that the work by Lewis Sheiner reflected in the FDA document
      titled "Innovation or Stagnation: Challenge and Opportunity on the Critical Path
      to New Medical Products" made this scientific approach to the drug approval
      process possible.

PMID- 16283535
TI  - Analyzing multi-response data using forcing functions.
AB  - INTRODUCTION: Two analytic strategies can be taken to the analysis of multi
      response data: a multivariate output model can be fit to all the response
      components simultaneously (SIM), or each response component can be fit separately
      to a univariate output model, conditioning in some way on the non-modeled
      components, the so-called forcing function approach (FFA). Focusing on a special
      case of multi-response model corresponding to a (pharmacokinetic) physiological f
      low model (PFM), the aims of this study are to (i) provide an algorithm for
      applying FFA to multi-response data from a PFM; (ii) examine the performance of
      FFA vs. SIM under optimal conditions for both, and in the presence of model
      misspecification; (iii) make recommendations regarding the use of FFA for multi
      response data analysis. METHODS: The basic PFM we use (variants of the basic
      model are used for simulation) has four homogenous compartments among which drug
      distributes. All are sampled arterial blood (A), non-eliminating tissue (N),
      eliminating tissue (E), and venous blood (V), which is also the drug dosing site.
      Parameters are blood f low rates to E and N, volumes of distribution of A, E, N,
      and V, elimination rate constant from E, and observation error variances.
      Observations from a generic individual under various study designs and parameter
      values are simulated. Using data-analytic models (DAM) both the same as, and
      different than the data simulation model (DSM), SIM fits the PFM to all data
      simultaneously; FFA first fits each type of response (one per tissue) separately,
      approximating the tissue's input by linearly interpolating the observed
      concentrations from the donor tissue(s), estimates the identifiable parameter
      combinations for the response type, and then solves the simultaneous equations
      linking these across tissues, to obtain the primary model parameters of interest.
      This simulation and analysis steps are repeated to generate reliable performance
      statistics. Performances are compared with respect to parameter estimation error
      (when DAM and DSM are identical), and interpolated prediction error (when DAM and
      DSM are/are-not identical). The ability of SIM and FFA to identify the correct
      analytic model is also examined by comparing their failure rates in rejecting the
      wrong DAM. RESULTS: The parameter estimation errors with FFA are generally about
      two times greater than those with SIM when the DAM is identical to the DSM. The
      prediction errors of FFA are about ten times greater than those of SIM when the
      DAM is identical to the DSM, and are about three times greater when the two are
      different. However, SIM fails to identify the correct model twice as often as
      FFA. CONCLUSIONS: Despite its greater convenience for model building, and its
      clear advantages for model identification, FFA's final parameter estimates cannot
      be trusted when the multi-response system being modeled involves feedback. The
      size of the ratio of the two FFA residuals (obtained from the response-specific
      fits and from predictions made with the final FFA parameters) can, however, be
      used to indicate when FFA's final estimates may be trustworthy.

PMID- 16283537
TI  - Mixed effects versus fixed effects modelling of binary data with inter-subject
      variability.
AB  - The question of whether or not a mixed effects model is required when modelling
      binary data with inter-subject variability and within subject correlation was
      reported in this journal by Yano et al. (J. Pharmacokin. Pharmacodyn. 28:389-412
      [2001]). That report used simulation experiments to demonstrate that, under
      certain circumstances, the use of a fixed effects model produced more accurate
      estimates of the fixed effect parameters than those produced by a mixed effects
      model. The Laplace approximation to the likelihood was used when fitting the
      mixed effects model. This paper repeats one of those simulation experiments, with
      two binary observations recorded for every subject, and uses both the Laplace and
      the adaptive Gaussian quadrature approximations to the likelihood when fitting
      the mixed effects model. The results show that the estimates produced using the
      Laplace approximation include a small number of extreme outliers. This was not
      the case when using the adaptive Gaussian quadrature approximation. Further
      examination of these outliers shows that they arise in situations in which the
      Laplace approximation seriously overestimates the likelihood in an extreme region
      of the parameter space. It is also demonstrated that when the number of
      observations per subject is increased from two to three, the estimates based on
      the Laplace approximation no longer include any extreme outliers. The root mean
      squared error is a combination of the bias and the variability of the estimates.
      Increasing the sample size is known to reduce the variability of an estimator
      with a consequent reduction in its root mean squared error. The estimates based
      on the fixed effects model are inherently biased and this bias acts as a lower
      bound for the root mean squared error of these estimates. Consequently, it might
      be expected that for data sets with a greater number of subjects the estimates
      based on the mixed effects model would be more accurate than those based on the
      fixed effects model. This is borne out by the results of a further simulation
      experiment with an increased number of subjects in each set of data. The
      difference in the interpretation of the parameters of the fixed and mixed effects
      models is discussed. It is demonstrated that the mixed effects model and
      parameter estimates can be used to estimate the parameters of the fixed effects
      model but not vice versa.

PMID- 16283536
TI  - Non-linear mixed effects modeling - from methodology and software development to
      driving implementation in drug development science.
AB  - Few scientific contributions have made significant impact unless there was a
      champion who had the vision to see the potential for its use in seemingly
      disparate areas-and who then drove active implementation. In this paper, we
      present a historical summary of the development of non-linear mixed effects
      (NLME) modeling up to the more recent extensions of this statistical methodology.
      The paper places strong emphasis on the pivotal role played by Lewis B. Sheiner
      (1940-2004), who used this statistical methodology to elucidate solutions to real
      problems identified in clinical practice and in medical research and on how he
      drove implementation of the proposed solutions. A succinct overview of the
      evolution of the NLME modeling methodology is presented as well as ideas on how
      its expansion helped to provide guidance for a more scientific view of (model
      based) drug development that reduces empiricism in favor of critical quantitative
      thinking and decision making.

PMID- 16283538
TI  - Modelling a spontaneously reported side effect by use of a Markov mixed-effects
      model.
AB  - AIMS: To present a method for analyzing side-effect data where change in severity
      is spontaneously reported during the experiment. METHODS: A clinical study in 12
      healthy volunteers aimed to investigate the concentration-response
      characteristics of a CNS-specific side-effect was conducted. After an open
      session where the subjects experienced the side-effect and where the individual
      pharmacokinetic parameters were evaluated they were randomized to a sequence of
      three different infusion rates of the drug in a double-blinded crossover way. The
      infusion rates were individualized to achieve the same target concentration in
      all subjects and different drug input rates were selected to mimic absorption
      profiles from different formulations. The occurrence of the specific side-effect
      and any subsequent change in severity was self-reported by the subjects. Severity
      was recorded as 0 = no side-effect, 1 = mild side-effect and 2 = moderate or
      severe side-effect. RESULTS: The side-effect data were analyzed using a mixed
      effects model for ordered categorical data with and without Markov elements. The
      former model estimated the probability of having a certain side-effect score
      conditioned on the preceding observation and drug exposure. The observed numbers
      of transitions between scores were from 0 -> 1: 24, from 0- > 2: 11, from 1 - >,
      2: 23, from 2- > 1: 1, from 2- > 0: 32 and from 1 - >0: 2. The side-effect model
      consisted of an effect-compartment model with a tolerance compartment. The
      predictive performance of the Markov model was investigated by a posterior
      predictive check (PPC), where 100 datasets were simulated from the final model.
      Average number of the different transitions from the PPC was from 0 - > 1: 26,
      from 0 - > 2: 11, from 1 - > 2: 25, from 2 - >1: 1, from 2 - >0: 35 and from 1 -
      > 0: 1. A similar PPC for the model without Markov elements was at considerable
      disparity with the data. CONCLUSION: This approach of incorporating Markov
      elements in an analysis of spontaneously reported categorical side-effect data
      could adequately predict the observed side-effect time course and could be
      considered in analyses of categorical data where dependence between observations
      is an issue.

PMID- 16283539
TI  - Getting the Dose Right: report from the Tenth European Federation of
      Pharmaceutical Sciences (EUFEPS) conference on optimizing drug development.
AB  - This report highlights the main points emerging from a meeting sponsored on
      "Getting the Dose Right" in clinical development, jointly sponsored by the
      European Federation of Pharmaceutical Sciences and the European Center of
      Pharmaceutical Medicine, as part of the Workshop Series on Frontiers in Drug
      Development, in Basel, Switzerland on December 9-12, 2002.

PMID- 16283540
TI  - Do you need to care to be caring?

PMID- 16283541
TI  - Accounting for differing exposure patterns between laboratory tests and the field
      in the assessment of long-term risks of pesticides to terrestrial vertebrates.
AB  - Long-term risks of pesticides to birds and mammals are currently assessed by
      comparing effects thresholds determined in chronic laboratory studies to exposure
      levels expected to occur in the field. However, there is often a mismatch between
      exposure patterns tested in the laboratory tests (exposure levels held constant)
      and those experienced by animals in the field (exposure levels varying over
      time). Three methods for addressing this problem are presented and discussed.
      Time-weighted averaging (TWA) converts a variable field exposure regime to a
      single value that can be compared directly to the laboratory test results. Body
      burden modeling (BBM) is applied to both laboratory and field exposure regimes
      allowing a straightforward comparison of body residue levels expected for each
      situation. Temporal analysis (TA) uses expert judgment to decide if the length of
      time exposure exceeds a toxicity threshold is long enough to cause biologically
      significant effects. To reduce uncertainty in long-term assessments, the conduct
      of specialized laboratory tests in which test subjects are administered a time
      varying exposure that mimics what occurs in the field should be considered. Such
      tests may also be useful testing the validity of each of these assessment
      methods.

PMID- 16283542
TI  - Quantitative structure-activity relationships for the pre-steady state of
      Pseudomonas species lipase inhibitions by p-nirophenyl-N-substituted carbamates.
AB  - The pre-steady states of Pseudomonas species lipase inhibitions by p-nitrophenyl
      N-substituted carbamates (1-6) are composed of two steps: (1) formation of the
      non-covalent enzyme-inhibitor complex (E:I) from the inhibitor and the enzyme and
      (2) formation of the tetrahedral enzyme-inhibitor adduct (E-I) from the E:I
      complex. From a stopped-flow apparatus, the dissociation constant for the E:I
      complex, KS, and the rate constant for formation of the tetrahedral E-I adduct
      from the E:I complex, k2 are obtained from the non-linear least-squares of curve
      fittings of first-order rate constant (k(obs)) versus inhibition concentration
      ([I]) plot against k(obs)=k2+k2[I]/(KS+[I]). Values of pKS, and log k2 are
      linearly correlated with the sigma* values with the rho* values of -2.0 and 0.36,
      respectively. Therefore, the E:I complexes are more positive charges than the
      inhibitors due to the rho* value of -2.0. The tetrahedral E-I adducts on the
      other hand are more negative charges than the E:I complexes due to the rho* value
      of 0.36. Formation of the E:I complex from the inhibitor and the enzyme are
      further divided into two steps: (1) the pre-equilibrium protonation of the
      inhibitor and (2) formation of the E:I complex from the protonated inhibitor and
      the enzyme.

PMID- 16283543
TI  - An unstructured region is required by GAV homologue for the fibrillization of
      host proteins.
AB  - Accumulating evidence shows that some amyloidogenic proteins contain core
      sequences, which are critical for their fibrillization. Core sequences of alpha
      synuclein, beta-amyloid peptide and prion protein usually reside in their
      unfolded regions and share a conserved consensus (VGGAVVAGV) designated as GAV
      homologue. Here we investigate the role of unfolded regions in fibrillization
      after GAV homologue is attached to the C-terminus or inserted into the loop
      regions of different host proteins, namely alpha -Syn1-65, gamma-synuclein, E.
      coli thioredoxin and immunoglobulin G binding B1 domain of streptococcal protein
      G. The results imply that an unstructured region is required by GAV homologue for
      the fibrillization of host proteins. A number of amyloidogenic proteins with core
      sequences located in unstructured regions are summarized and discussed in
      details. The finding may provide further insight into the elucidating of the
      molecular mechanism underlying the fibrillization of alpha-Syn, Abeta and PrP as
      well as other amyloidogenic proteins.

PMID- 16283544
TI  - Analysis of substrate specificity and endopeptidyl activities of the cathepsin B
      like proteinase from Helicoverpa armigera.
AB  - The cathepsin B-like proteinase from Helicoverpa armigera (HCB) is involved in
      the degradation of yolk proteins during embryonic development. In order to gain
      insight into the substrate specificity of this proteinase, various proteins from
      animals and plants were tested as substrates. The specific cleavage sites of this
      enzyme on endopeptide bonds were assayed using bovine serum albumin (BSA) as a
      substrate. Results showed that BSA was degraded into several fragments, which
      suggests that HCB cleaves BSA at specific endopeptidyl sites. The amino acid
      sequences of the BSA derived peptides were determined, revealing cleavage of the
      bonds between residues Arg81-Glu82, Val423-Glu424 and Gly430-Lys431. This
      suggests that the minimum requirement for a scissile bond to be recognized by HCB
      is the presence of an ionic amino acid at the P1 ' position and the P1 position
      can vary. These observations suggest that HCB cleaves bonds at the N-terminal
      side of ionic amino acid residues giving HCB a wide range of substrates, though
      other factors dictating the substrate specificity of this enzyme remains to be
      clarified. Our results provide new evidence that HCB functions as an
      endopeptidase on some proteins.

PMID- 16283545
TI  - The formation of casein micelles reconstituted with Ca+2 and added inorganic
      phosphate is influenced by the non-phosphorylated form of human beta-casein.
AB  - The beta-casein (CN) human milk fraction is comprised of a single protein
      phosphorylated at levels from 0 to 5. Component interactions are dependent on the
      phosphorylation level. Here, 3 mg/ml of beta-CN-0P, beta-CN-2P, beta-CN-4P, a
      2P/4P 1:1 (wt:wt) mixture, or a mixture of all six forms in the ratio in human
      milk, were mixed with bovine kappa-CN at a kappa/beta molar ratio of 0.33.
      Measurements were with 0, 5 and 10 mM Ca+2 and 4 and 8 mM added inorganic
      phosphate (Pi). The turbidity (OD400 nm) and a lack of precipitation as T
      increased from 4 to 37 degrees C was an index of micelle formation. The results
      indicate: (1) while micelles will form with Ca+2 alone, added Pi has a
      significant enhancing effect on micelle formation; (2) the patterns of micelle
      formation as a function of T are influenced by the beta-CN-0P and beta-CN-1P
      forms of beta-CN to an unexpected extent.

PMID- 16283546
TI  - Biochemical, pharmacological and structural characterization of a new PLA2 from
      Crotalus durissus terrificus (South American rattlesnake) venom.
AB  - A new PLA2 (F16) was purified from Crotalus durissus terrificus venom by
      molecular exclusion chromatography followed by analytical reverse phase HPLC. The
      PLA2 (14.86 kDa by MALDI-TOF mass spectrometry) had an amino acid sequence of
      SLLQFNKMIKFETRKNAVPFYAFYGCYCGWGGRRRPKDATDRCCFVHDCCYEKVTKCNTKWDIYRYSLKSGYITCGKGTWC
      EQICECDRVAAECLRRSLSTYKNGYMFYPDSRCRGPSETC, and showed highly conserved Ca2+
      binding and catalytic sites. F16 showed allosteric behavior with 10 mM Ca2+ and
      had temperature and pH optima of 25 degrees C and 7.9, respectively. F16 (10
      microg/ml) produced neuromuscular blockade in chick biventer cervicis
      preparations in the absence and presence of crotapotin, indicating that
      crotapotin was not essential for neuromuscular action in this preparation. In
      contrast, in mouse phrenic nerve-diaphragm preparations, the neuromuscular
      blockade produced by the same concentration of toxin was dependent on crotapotin.
      Pre-incubation with heparin markedly reduced the neurotoxicity of F16. These
      results show that the biochemical and structural properties of F16 are similar to
      those of the PLA2 isoforms F15 and F17, but that the neurotoxicity and the
      requirement for crotapotin to form the crotoxin complex varies according to the
      neuromuscular preparation.

PMID- 16283547
TI  - Preparation and characterization of a truncated caricain lacking 41 residues from
      the N-terminal.
AB  - We purified an 18.8 kD protease from caricain solution. This protease was derived
      from caricain. It does not have the first 41 residues of the N-terminal sequence
      of caricain, and its N-terminal residue is Thr. Also, one of the disulfide bonds
      of caricain (cys22-cys63) was opened during the formation of the protease. We
      named this 18.8 kD protease caricain II. Caricain II has a wide pH range, and it
      is more sensitive to temperature changes than caricain. The proteolytic activity
      of caricain II is twice as much as that of caricain using casein as a substrate.
      However, caricain II has a low hydrolytic activity with N-benzoyl-L-arginine
      ethyl ester (BAEE) that is one of the special substrates of caricain. Our results
      indicate that caricain II is remarkably different from caricain and it can
      provide an improvement over caricain on the proteolytic activity.

PMID- 16283548
TI  - Specificity of inhibition of ras-p21 signal transduction by peptides from GTPase
      activating protein (GAP) and the son-of sevenless (SOS) ras-specific guanine
      nucleotide exchange protein.
AB  - In previous studies, involving molecular modeling of wild-type and oncogenic
      forms of the ras-p21 protein bound to GTPase activating protein GAP and the ras
      specific guanine nucleotide exchange-promoting protein, SOS, we identified
      specific domains of GAP and SOS proteins that differ in conformation when the
      computed average structures of the corresponding wild-type and oncogenic
      complexes are superimposed. Additionally, in these previous studies, we have
      synthesized peptides corresponding to these domains and found that all of them
      inhibit either or both oncogenic (Val 12-containing) p21- and insulin-activated
      wild-type p21-induced oocyte maturation. To document further the specificity of
      the inhibition of these peptides for the ras signal transduction pathway, we have
      now tested their effects on progesterone-induced maturation that occurs by a ras
      independent pathway. None of these peptides, including a peptide corresponding to
      residues 980-989 of SOS that completely blocks oncogenic p21-induced maturation
      and also causes extensive inhibition of insulin-induced maturation, affects
      progesterone-induced maturation, suggesting that all of these peptides are
      specific for the ras pathway. Since our approach to the design of peptides that
      can inhibit oncogenic ras-p21 selectively is based on identifying domains that
      differ in conformation between oncogenic and wild-type complexes, we have now
      further synthesized peptides that correspond to domains of GAP (residues 903-910)
      and SOS (residues 792-804) that do not differ in conformation when the average
      structures are superimposed. These peptides do not inhibit either oncogenic p21-
      or insulin-induced oocyte maturation, supporting the overall strategy of using
      peptides from domains that change conformation as the ones most likely to inhibit
      oncogenic and/or wild-type ras-p21. These results further support the specificity
      of inhibition of the GAP and SOS peptides from the conformationally distinct
      domains of both proteins.

PMID- 16283550
TI  - Thyroid hormone and the energetic cost of keeping body temperature.

PMID- 16283551
TI  - Control and regulatory mechanisms associated with thermogenesis in flying insects
      and birds.
AB  - Most insects and birds are able to fly. The chitin made exoskeleton of insects
      poses them several constraints, and this is one the reasons they are in general
      small sized animals. On the other hand, because birds possess an endoskeleton
      made of bones they may grow much larger when compared to insects. The two taxa
      are quite different with regards to their general "design" platform, in
      particular with respect to their respiratory and circulatory systems. However,
      because they fly, they may share in common several traits, namely those
      associated with the control and regulatory mechanisms governing thermogenesis.
      High core temperatures are essential for animal flight irrespective of the taxa
      they belong to. Birds and insects have thus evolved mechanisms which allowed them
      to control and regulate high rates of heat fluxes. This article discusses
      possible convergent thermogenic control and regulatory mechanisms associated with
      flight in insects and birds.

PMID- 16283552
TI  - Role of sarco/endoplasmic reticulum Ca(2+)-ATPase in thermogenesis.
AB  - Enzymes are able to handle the energy derived from the hydrolysis of phosphate
      compounds in such a way as to determine the parcel that is used for work and the
      fraction that is converted into heat. The sarco/endoplasmic reticulum Ca(2+)
      ATPases (SERCA) is a family of membrane-bound ATPases that are able to transport
      Ca(2+) ion across the membrane using the chemical energy derived from ATP
      hydrolysis. The heat released during ATP hydrolysis by SERCA may vary from 10 up
      to 30 kcal/mol depending on the SERCA isoform used and on whether or not a Ca(2+)
      gradient is formed across the membrane. Drugs such as heparin, dimethyl sulfoxide
      and the platelet-activating factor (PAF) are able to modify the fraction of the
      chemical energy released during ATP hydrolysis that is used for Ca(2+) transport
      and the fraction that is dissipated in the surrounding medium as heat. The
      thyroid hormone 3,5,3'-triiodo L: -thyronine (T(3)) regulates the expression and
      function of the thermogenic SERCA isoforms. Modulation of heat production by
      SERCA might be one of the mechanisms involved in the increased thermogenesis
      found in hyperthyroidism.

PMID- 16283553
TI  - Adaptive activation of thyroid hormone and energy expenditure.
AB  - The mechanisms by which thyroid hormone accelerates energy expenditure are poorly
      understood. In the brown adipose tissue (BAT), activation of thyroid hormone by
      type 2 iodothyronine deiodinase (D2) has been known to play a role in adaptive
      energy expenditure during cold exposure in human newborns and other small
      mammals. Although BAT is not present in significant amounts in normal adult
      humans, recent studies have found substantial amounts of D2 in skeletal muscle, a
      metabolically relevant tissue in humans. This article reviews current biological
      knowledge about D2 and adaptive T3 production and their roles in energy
      expenditure.

PMID- 16283554
TI  - Genomic structure and regulation of mitochondrial uncoupling protein genes in
      mammals and plants.
AB  - Uncoupling mitochondrial proteins (UCPs) belong to a discrete family within the
      mitochondrial anion carrier superfamily. Several uncoupling protein types have
      been found in mitochondria from mammals and plants, as well as in fishes, fungi,
      and protozoa. Mammalian UCPs and plant uncoupling proteins (PUMPs) form five
      distinct subfamilies. Only subfamily III contains both plant and animal
      uncoupling proteins, as well as UCPs from primitive eukaryotic organisms, which
      suggest that this group may represent an ancestral cluster from which other
      UCPs/PUMPs may have evolved. Genetic data indicate that UCPs/PUMPs are regulated
      at the transcriptional, post-transcriptional, and translational levels.
      Tissue/organ- and stress-specific gene expression suggests that UCPs/PUMPs are
      involved in the general balance of basic energy expenditure, protection against
      reactive oxygen species, and thermogenesis. Finally, the simultaneous occurrence
      of PUMP and alternative oxidase, another energy-dissipating system in plant
      mitochondria, raises the question of their response to biotic and abiotic stress
      at the transcriptional and functional levels.

PMID- 16283555
TI  - Thermoregulation: what role for UCPs in mammals and birds?
AB  - Mammals and birds are endotherms and respond to cold exposure by the means of
      regulatory thermogenesis, either shivering or non-shivering. In this latter case,
      waste of cell energy as heat can be achieved by uncoupling of mitochondrial
      respiration. Uncoupling proteins, which belong to the mitochondrial carrier
      family, are able to transport protons and thus may assume a thermogenic function.
      The mammalian UCP1 physiological function is now well understood and gives to the
      brown adipose tissue the capacity for heat generation. But is it really the case
      for its more recently discovered isoforms UCP2 and UCP3? Additionally, whereas
      more and more evidence suggests that non-shivering also exists in birds, is the
      avian UCP also involved in response to cold exposure? In this review, we consider
      the latest advances in the field of UCP biology and present putative functions
      for UCP1 homologues.

PMID- 16283556
TI  - Neonatal programming of body weight regulation and energetic metabolism.
AB  - Programming is an epigenetic phenomena by which nutritional, hormonal, physical
      psychological and other stressful events acting in a critical period of life,
      such as gestation and lactation, modifies in a prolonged way certain
      physiological functions. This process was preserved by natural selection as an
      important adaptive tool for survival of organisms living in nutritional impaired
      areas. So, malnutrition during gestation and lactation turns on different genes
      that provide the organism with a thrifty phenotype. In the case of an abundant
      supply of nutrients after this period, those organisms that were adapted to a low
      metabolic waste and higher energy utilization will be in a higher risk of
      developing metabolic diseases, such as obesity, hyperlipidemia, diabetes mellitus
      and hypertension. The kind of malnutrition, duration and intensity are important
      for the type of programming obtained. We discuss some of the hormonal and
      metabolic changes that occur in gestation or lactation, when malnutrition is
      applied to the mothers and their offspring. Some of these changes, such as an
      increase of maternal triiodothyronine (T(3)), leptin and glucocorticoids (GC) and
      decrease in prolactin are by itself potential programming factors. Most of these
      hormones can be transfer through the milk that has other important macronutrients
      composition changes in malnourished dams. We discuss the programming effects of
      some of these hormones upon body weight and composition, leptin, thyroid and
      adrenal functions, and their effects on liver, muscle and adipose tissue
      metabolism and the consequences on thermogenesis.

PMID- 16283557
TI  - Plant uncoupling mitochondrial protein and alternative oxidase: energy metabolism
      and stress.
AB  - Energy-dissipation in plant mitochondria can be mediated by inner membrane
      proteins via two processes: redox potential-dissipation or proton electrochemical
      potential-dissipation. Alternative oxidases (AOx) and the plant uncoupling
      mitochondrial proteins (PUMP) perform a type of intrinsic and extrinsic
      regulation of the coupling between respiration and phosphorylation, respectively.
      Expression analyses and functional studies on AOx and PUMP under normal and
      stress conditions suggest that the physiological role of both systems lies most
      likely in tuning up the mitochondrial energy metabolism in response of cells to
      stress situations. Indeed, the expression and function of these proteins in non
      thermogenic tissues suggest that their primary functions are not related to heat
      production.

PMID- 16283560
TI  - Anal fissure and minor anorectal sepsis after stapled hemorrhoidectomy.

PMID- 16283561
TI  - Expectant management of anal squamous dysplasia in patients with HIV.
AB  - PURPOSE: Anal squamous dysplasia is commonly found in patients with HIV
      infection. There is no satisfactory treatment that eradicates this premalignant
      lesion with low morbidity and low recurrence. This study reviews a series of
      patients with HIV and an abnormal anal examination who had squamous dysplasia and
      who have been followed with physical examination alone and with repeat biopsies
      as necessary for new or suspicious lesions. METHODS: We reviewed the charts of 40
      HIV-positive men who had squamous dysplasia of the anal canal and anal margin,
      focusing on history, physical findings, histologic diagnosis, and the occurrence
      of invasive squamous-cell carcinoma. RESULTS: Forty HIV-positive men (mean age,
      39 years) were followed for anal squamous dysplasia. Biopsies revealed dysplasia,
      which was usually multifocal. The grade of dysplasia varied, but 28 of 40
      patients had at least one area of severe dysplasia. All patients had a follow-up
      period greater than one year (mean, 32 months; range, 13-130 months). Three
      patients developed invasive carcinoma while under surveillance, and these were
      completely excised or cured with chemoradiation. CONCLUSIONS: Extensive excision
      for dysplasia in the context of HIV confers high morbidity and questionable
      benefit, and other treatments are of uncertain value. In a group of patients
      followed expectantly, most did not develop invasive cancer, and in those who did,
      early cancers could be identified and cured. Physical examination surveillance
      for invasive carcinoma may be acceptable for following patients with HIV and
      biopsy-proven squamous dysplasia.

PMID- 16283562
TI  - Outcomes for abdominoperineal resections are not worse than those of anterior
      resections.
AB  - PURPOSE: Local recurrence and cure rates following abdominoperineal resections
      have been reported to be much worse than sphincter-preserving anterior
      resections. We compared the oncologic outcomes of patients treated by
      abdominoperineal resections with those following sphincter-preserving anterior
      resections. METHODS: The medical records of patients who underwent radical rectal
      resection for rectal carcinoma at the Colorectal Surgery Department, Singapore
      General Hospital, during the period from April 1989 to April 2002 were reviewed.
      A total of 791 cases were studied. Operative procedures were classified as either
      abdominoperineal resections or anterior resections with either straight or pouch
      anastomosis. Total mesorectal excision was routinely performed for carcinomas of
      the lower middle and lower third of the rectum. Sentinel events, including local
      and systemic recurrences or morbidity and mortality, were tracked prospectively.
      RESULTS: There were a total of 93 abdominoperineal resections (12.1 percent), 547
      anterior resections with straight anastomoses (71 percent), and 130 anterior
      resections with pouch anastomoses (16.9 percent). Postoperative mortality was 2.6
      percent and postoperative morbidity was 13.6 percent with an overall anastomotic
      leakage rate of 2.5 percent. The cumulative five-year local recurrence rate was
      5.4 percent for abdominoperineal resections, 3.6 percent for anterior resections
      with straight anastomoses, and 3.8 percent for anterior resections with pouch
      anastomoses (P = 0.73 by log-rank test). The median time to local recurrence also
      did not differ significantly between the different procedures (abdominoperineal
      resections, 17 months, anterior resections with straight anastomoses, 18 months,
      anterior resections with pouch anastomoses, 13 months). Independent predictors
      for local recurrence included advanced tumor stage, tumor depth, and poorly
      differentiated tumors. The five-year cancer-specific survival was 70 percent. The
      type of anastomosis did not influence disease-free survival with median disease
      free survival for patients who underwent abdominoperineal resections being 100
      months, survival of anterior resections with straight anastomoses being 135
      months, and survival of anterior resections with pouch anastomoses being 121
      months (P = 0.33 by log-rank test). The independent factors for poor survival
      were age greater than 65 years, advanced tumor stage, tumor depth, and poorly
      differentiated tumors. CONCLUSION: Both abdominoperineal resections and sphincter
      preserving anterior resections can be performed safely with low morbidity and
      mortality in a specialized high-volume hospital unit without compromising
      oncologic outcomes. With appreciation of the anatomic relations in total
      mesorectal excision and standardized consistent surgical technique, the oncologic
      outcomes of patients treated by abdominoperineal resections are not worse than
      those treated by sphincter-preserving anterior resections.

PMID- 16283563
TI  - Management of pilonidal sinus disease with oblique excision and primary closure:
      results of 493 patients.
AB  - PURPOSE: Pilonidal sinus disease is a common and well-known entity. Many surgical
      methods have been described for the treatment of pilonidal sinus disease. The aim
      of this study was to determine the advantages and long-term results of oblique
      excision and primary closure techniques. METHOD: Between January 1999 and
      December 2001, 493 patients (490 male, 3 female; average age = 23.48 +/- 3.90
      (range, 15-51) years) were operated on for primary or recurrent pilonidal sinus
      disease. An oblique fusiform-shaped incision was made and the skin was excised.
      The operation was completed with primary closure. All patients' follow-up
      examinations were made at the end of the 6 weeks and 3, 6, 12, and 18 months
      after surgery. RESULTS: The mean duration of symptoms was 22.09 +/- 17.12 (range,
      1-120) months. The mean duration of hospital stay was 5.51 +/- 2.85 (range, 2-17)
      days. At the end of the follow-up period, the recurrence rate was 5.6 percent.
      CONCLUSION: The ideal operation for pilonidal sinus disease treatment must be
      simple and effective. The technique of oblique excision and primary closure may
      be considered an alternative operation for pilonidal sinus resulting in a low
      recurrence rate.

PMID- 16283564
TI  - Metastatic cutaneous Crohn's disease of the nipple: report of a case.
AB  - A case of cutaneous Crohn's disease involving the right breast and presenting as
      multiple periareolar fistulas in a 46-year-old female is reported. The lesion had
      initially been diagnosed and treated as a simple abscess. She had a 26-year
      history of Crohn's disease with numerous hospitalizations for bowel resections
      and control of diarrhea. Histopathologic examination following excision of the
      fistulas and total duct excision, however, showed well-defined granulomas
      containing multinucleated giant cells characteristic of extraintestinal Crohn's
      disease.

PMID- 16283565
TI  - Preoperative steroid-related complications in Japanese pediatric patients with
      ulcerative colitis.
AB  - PURPOSE: This study was designed to clarify a limit for steroid therapy in
      patients with ulcerative colitis through analyzing the preoperative major steroid
      related complications and to define when alternative therapies, including
      surgery, should be performed in pediatric ulcerative colitis patients. METHODS:
      The medical records of 28 pediatric and 57 adult patients with ulcerative colitis
      who underwent total proctocolectomy and ileal J-pouch-anal anastomosis were
      reviewed. The relationship between the preoperative dose of glucocorticoids and
      major steroid-related complications, as well as the surgery variables, was
      evaluated. RESULTS: Significantly higher incidences of growth retardation,
      osteoporosis, glaucoma, and cataracts were noted in pediatric patients than in
      adult patients. In pediatric patients, major steroid-related complications
      occurred at a significantly lower preoperative total dosage of
      glucocorticoids/body weight (mg/kg) or preoperative total dosage of
      glucocorticoids/body surface area (mg/m2) than in adult patients. A similar
      surgical procedure was performed in both pediatric and adult patients. The
      presence of major steroid-related complications can lower a patient's long-term
      quality of life. CONCLUSIONS: Evidence-based guidelines for the recommended dose
      of glucocorticoids according to body weight or body surface area are needed. To
      allow patients to feel well and maintain a good quality of life, early
      introduction of alternative treatments, including surgery, should be considered.

PMID- 16283566
TI  - Comparison of characteristics and survival of colorectal cancer between Japanese
      Americans in Hawaii and native Japanese in Japan.
AB  - PURPOSE: This study was designed to investigate whether characteristics,
      prognostic risk factors, and survival of colorectal cancer of Japanese-Americans
      in Hawaii are different from those of native Japanese in Japan. METHODS: A
      retrospective review of patients with colorectal cancer surgically resected in
      single institutions in Hawaii and Japan from 1996 to 2002. RESULTS: A total of
      410 Japanese-American patients (218 males; median age, 73 years) and 621 native
      Japanese patients (382 males; median age, 65 years) were included. There were
      significant differences in age (P < 0.001), age distribution (P < 0.001), gender
      (P = 0.008), preoperative carcinoembryonic antigen (P < 0.001), and anatomic site
      distribution (P < 0.001). The tumor characteristics of Japanese-American patients
      were close to the general American population compared with the Surveillance,
      Epidemiology, and End Results data. There were no differences in tumor size,
      histologic grade, each of T, N, M status and TNM stage between the two groups.
      The overall five-year survival rates (Japanese-Americans, 75.5 percent; native
      Japanese, 76.2 percent; P = 0.55) and survival rates in each of four stratified
      stages were similar. Risk factors associated with survival were not different,
      except for carcinoembryonic antigen (P = 0.036). CONCLUSIONS: In patients with
      colorectal cancer in Japanese-Americans in Hawaii, some of tumor characteristics
      have changed from those of native Japanese in Japan. However, there are no
      remarkable differences in prognostic factors and survival between the two groups.
      The present study suggests that certain changes of colorectal cancer
      characteristics that were seen in Japanese-American may occur in native Japanese
      in Japan in the near future, although the survival outcome of colorectal cancer
      may remain the same.

PMID- 16283567
TI  - Stapled hemorrhoidopexy: a new device and method of performance without using a
      pursestring suture.
AB  - PURPOSE: This study was designed to develop a more reliable device and technique
      that will allow for the safer and reproducibly consistent performance of a
      stapled hemorrhoidopexy without using a pursestring suture. This device and
      technique must allow the surgeon to be able to control the volume of tissue drawn
      into the stapler center chamber during the performance of the procedure. METHODS:
      A porcine model was used to evaluate and perfect a mucosal impalement device and
      technique for use during the performance of a stapled hemorrhoidopexy. A
      specially manufactured washer with spikes on one side was fitted onto the center
      shaft of a PROXIMATE PPH01 Hemorrhoidal Circular Stapler and was used in each of
      nine animals. A pursestring suture was not needed and was not used in any of the
      procedures. RESULTS: After performing the stapled hemorrhoidopexy, a mucosal
      donut was obtained from each animal. On gross inspection, each donut was of
      similar size, height, and volume compared with that of a human stapled
      hemorrhoidopexy donut. Each was completely circumferential (except for the final
      specimen, which was purposely incomplete after having performed a single quadrant
      resection). The performance of each procedure required approximately one minute.
      CONCLUSIONS: A procedure and device have been developed that allow for the rapid,
      safe, and reliable performance of a sutureless stapled hemorrhoidopexy by using a
      new mucosal impalement device and technique in the porcine model. It was used
      successfully in the porcine model under simulated diverse clinical circumstances.
      The procedure is easy to teach and learn and has potential applicability for use
      in humans.

PMID- 16283568
TI  - The role of molecular structure in the crystal polymorphism of local anesthetic
      drugs: crystal polymorphism of local anesthetic drugs, part X.
AB  - PURPOSE: This report is the resume of a comprehensive investigation on the solid
      state properties and the crystal polymorphism of the structurally homogenous
      class of local anesthetic drugs. The goal is to explore the relationship between
      crystal polymorphism and molecular structural features. METHODS: A salt form
      (mostly the hydrochloride) as well as the free base of 24 local anesthetics has
      been characterized by means of thermomicroscopy, differential scanning
      calorimetry, pycnometry, Fourier transform infrared, Fourier transform Raman, and
      solid-state NMR spectroscopies, as well as X-ray diffraction methods (single
      crystal, powder). RESULTS: Based on the thermochemical data, the relative
      thermodynamic stabilities of the different crystal forms of each polymorphic
      system were evaluated and visualized as semiquantitative energy/temperature
      diagrams. CONCLUSION: This study is the first step in recognizing relationships
      between the structure and the solid-state properties within this limited group of
      active substances with common structural elements. The results clearly show that
      there are certain relationships, but, to understand the phenomenological behavior
      in more detail on a molecular level, more structural information must be
      collected and analyzed by computational methods.

PMID- 16283569
TI  - Older age independently predicts a lower risk of sentinel lymph node metastasis
      in breast cancer.
AB  - BACKGROUND: The influence of patient age on the risk of sentinel lymph node (SLN)
      metastasis in breast cancer has not been defined. METHODS: A breast cancer SLN
      database was analyzed. Factors associated with SLN metastasis were assessed by
      multiple logistic regression modeling. Age, T stage, estrogen receptor status,
      HER-2/neu status, grade, angiolymphatic invasion, lobular histology,
      tubular/mucinous histology, and the number of SLNs resected were assessed.
      RESULTS: Data were available for 810 patients with invasive breast cancer. SLN
      metastasis was observed in 22% of the patients. The factors most strongly
      associated with SLN metastasis were angiolymphatic invasion, T stage, and age.
      Age ranged from 29 to 95 years. The median age was 66 years. Overall, SLN
      metastasis was more common in younger patients (< or =66 years) than in older
      patients (>66 years; P < .001). Among patients without angiolymphatic invasion,
      SLN metastasis was nearly twice as common in the younger patients as in the older
      patients. The effect of angiolymphatic invasion as a risk for SLN metastasis was
      much greater in the older age group. CONCLUSIONS: In addition to known risk
      factors, age independently predicts the risk of SLN metastasis in breast cancer.
      Angiolymphatic invasion seems to be a more powerful predictor of SLN metastasis
      in older patients.

PMID- 16283571
TI  - Compartmental bone morphometry in the mouse femur: reproducibility and resolution
      dependence of microtomographic measurements.
AB  - Microcomputed tomography (microCT) is widely used for nondestructive bone
      phenotyping in small animals, especially in the mouse. Here, we investigated the
      reproducibility and resolution dependence of microCT analysis of microstructural
      parameters in three different compartments in the mouse femur. Reproducibility
      was assessed with respect to precision error (PE%CV) and intraclass correlation
      coefficient (ICC). We examined 14 left femurs isolated postmortem from two
      strains of mice (seven per group). Measurements and analyses were repeated five
      times on different days. In a second step, analysis was repeated again five times
      for a single measurement. Resolution dependence was assessed by high-resolution
      measurements (10 microm) in one strain and subsequent image degrading.
      Reproducibility was better in full bone compartment and in cortical bone
      compartment in the diaphysis (PE%CV = 0.06-2.16%) than in trabecular compartment
      in the distal metaphysis (PE(%CV) = 0.59-5.24%). Nevertheless, ICC (0.92-1.00)
      showed a very high reliability of the assessed parameters in all regions,
      indicating very small variances within repeated measurements compared to the
      population variances. Morphometric indices computed from lower- and higher
      resolution images displayed in general only weak dependence and were highly
      correlated with each other (R2 = 0.91-0.99). The results show that parameters in
      the full and cortical compartments were very reproducible, whereas precision in
      the trabecular compartment was somewhat lower. Nevertheless, all compartmental
      analysis methods were very robust, as shown by the high ICC values, demonstrating
      high suitability for application in inbred strains, where highest precision is
      needed due to small population variances.

PMID- 16283570
TI  - Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte
      associated antigen 4 blockade and interleukin 2: a phase I/II study.
AB  - BACKGROUND: Cytotoxic T lymphocyte-associated antigen (CTLA)-4 can inhibit T-cell
      responses and is involved in tolerance against self antigens. We previously
      reported autoimmune manifestations and objective cancer regressions in patients
      with metastatic melanoma treated with CTLA-4 blockade. The possibility of
      activating tumor-reactive T cells while removing inhibitory activity with CTLA-4
      blockade has stimulated interest in using anti-CTLA-4 antibodies in combination
      with other cancer immunotherapies to improve clinical outcomes. In this study, we
      assessed the antitumor activity and autoimmune toxicity of CTLA-4 blockade in
      combination with an immune-activating stimulus, interleukin (IL)-2, in patients
      with metastatic melanoma. METHODS: Thirty-six patients received anti-CTLA-4
      antibody every 3 weeks. Three patients per cohort received doses of .1, .3, 1.0,
      and 2.0 mg/kg. Twenty-four patients received 3.0 mg/kg. All patients received IL
      2 therapy (720,000 IU/kg every 8 hours to a maximum of 15 doses). RESULTS: Eight
      patients (22%) experienced objective tumor responses (three complete and five
      partial), including metastases in the lungs, lymph nodes, mediastinum, and
      subcutaneous tissues. Six of the eight patients have ongoing objective responses
      at 11 to 19 months. Five patients (14%) developed grade III/IV autoimmune
      toxicities secondary to anti-CTLA-4 administration, including four patients with
      enterocolitis and one with arthritis and uveitis. CONCLUSIONS: There is not
      evidence to support a synergistic effect of CTLA-4 blockade plus IL-2
      administration, because the 22% objective response rate is that expected from the
      sum of these two agents administered alone. Durable cancer regressions were seen
      in patients treated with this combination.

PMID- 16283572
TI  - Targeted disruption of two small leucine-rich proteoglycans, biglycan and
      decorin, excerpts divergent effects on enamel and dentin formation.
AB  - Small leucine-rich proteoglycans have been suggested to affect mineralization of
      dental hard tissues. To determine the functions of two of these small
      proteoglycans during the early stages of tooth formation, we characterized the
      dental phenotypes of biglycan (BGN KO) and decorin deficient (DCN KO) mice and
      compared them to that of wild type mice. Each targeted gene disruption resulted
      in specific effects on dentin and enamel formation. Dentin was hypomineralized in
      both knock out mice, although the effect was more prominent in the absence of
      decorin. Enamel formation was dramatically increased in newborn biglycan knockout
      mice but delayed in absence of decorin. Increased enamel formation in the former
      case resulted from an upregulation of amelogenin synthesis whereas delayed enamel
      formation in the later case was most probably an indirect consequence of the high
      porosity of the underlying dentin. Enamelin expression was unchanged in BGN KO,
      and reduced in DCN KO. Dentin sialoprotein (DSP), a member of the family of
      phosphorylated extracellular matrix proteins that play a role in dentinogenesis,
      was overexpressed in BGN-KO odontoblasts and in the sub-odontoblastic layer. In
      contrast, a decreased expression of DSP was detected in DCN KO. Dentin matrix
      protein-1 (DMP-1), bone sialoprotein (BSP) and osteopontin (OPN) were upregulated
      in BGN KO and downregulated in the DCN KO. Despite the strong effects induced by
      these deficiencies in newborn mice, no significant difference was detected
      between the three genotypes in adult mice, suggesting that the effects reported
      here in newborn mice are transient and subjected to self-repair.

PMID- 16283573
TI  - Endovascular repair of a traumatic axillary pseudoaneurysm following anterior
      shoulder dislocation.
AB  - Pseudoaneurysms due to musculoskeletal trauma are rare and comprise less than 2%
      of all pseudoaneurysms. We report a case of axillary pseudoaneurysm following
      anterior dislocation of the shoulder. The patient was successfully treated by
      endovascular intervention.

PMID- 16283574
TI  - Endovascular treatment of spontaneous isolated dissecting aneurysm of the
      superior mesenteric artery using stent-assisted coil embolization.
AB  - Spontaneous isolated dissecting aneurysm of the main trunk of the superior
      mesenteric artery is a rare condition. We treated a patient with this condition
      successfully by stent-assisted coil embolization. Intravascular stent placement
      may widen the indications for endovascular coiling of the aneurysmal false lumen
      to avoid perforation.

PMID- 16283575
TI  - Ruptured left gastric artery aneurysm: unique presentation with hemothorax and
      hemomediastinum.
AB  - Although splanchnic artery aneurysms are uncommon and remain mostly asymptomatic,
      they are associated with a high mortality rate when they rupture. We discuss the
      case of a 66-year-old woman who had successful embolization of a left gastric
      artery aneurysm after presenting with acute chest pain and the unusual computed
      tomography findings of hemothorax and hemomediastinum. To our knowledge, only one
      other similar case has been published in the literature.

PMID- 16283576
TI  - Lower energy endovenous laser ablation of the great saphenous vein with 980 nm
      diode laser in continuous mode.
AB  - PURPOSE: To assess clinical outcomes, complication rates, and unit energy applied
      using 980 nm diode endovenous laser treatment at 11 watts for symptomatic great
      saphenous vein (GSV) incompetence and reflux disease. METHODS: Thirty-four
      consecutive ablation therapies with a 980 nm diode endovenous laser at 11 watts
      were studied. The diagnosis of GSV incompetence with reflux was made by clinical
      evaluation and duplex Doppler examinations. The treated GSVs had a mean diameter
      of 1.19 cm (range 0.5-2.2 cm). The patients were followed with clinical
      evaluation and color flow duplex studies up to 18.5 months (mean 12.19 months +/-
      4.18). RESULTS: Using 980 nm diode endovenous laser ablation in continuous mode,
      100% technical success was noted. The mean length of GSVs treated was 33.82 cm
      (range 15-45 cm). The mean energy applied during the treatment was 1,155.81
      joules (J) +/- 239.50 (range 545.40-1620 J) for a mean treatment duration of
      90.77 sec +/- 21.77. The average laser fiber withdrawal speed was 0.35 cm/sec +/-
      0.054. The mean energy applied per length of GSV was 35.16 J/cm +/- 8.43. Energy
      fluence, calculated separately for each patient, averaged 9.82 J/cm(2) +/- 4.97.
      At up to 18.5 months follow-up (mean 12.19 months), 0% recanalization was noted;
      92% clinical improvement was achieved. There was no major complication. Minor
      complications included 1 patient with hematoma at the percutaneous venotomy site,
      1 patient with thrombophlebitis on superficial tributary varices of the treated
      GSV, 24% ecchymoses, and 32% self-limiting hypersensitivity/tenderness/"pulling"
      sensation along the treatment area. One patient developed temporary paresthesia.
      Four endovenous laser ablation treatments (12%) were followed by adjunctive
      sclerotherapies for improved cosmetic results. CONCLUSION: Endovenous laser
      ablation treatment of GSV using a 980 nm diode laser at 11 watts in continuous
      mode appears safe and effective. Mean energy applied per treated GSV length of
      35.16 J/cm or mean laser fluence of 9.82 J/cm(2) appears adequate, resulting in
      0% recanalization and low minor complication rates.

PMID- 16283577
TI  - "Pull and park": an alternative means of achieving hemostasis in percutaneous
      aspiration thrombectomy of an arteriovenous fistula for dialysis.

PMID- 16283579
TI  - Lipectomy of arms and lipograft of shoulders balance the upper body contour.
AB  - Lipodystrophies of upper limbs are less significant than lipodystrophies
      affecting inferior limbs, and the results of liposuction in that area are not
      always aesthetically acceptable. The authors topographically studied the amount
      of fat in a lipodystrophic arm of seven cadavers, and found that the zone located
      over the humerus' trochiter frequently presents lipodystrophic cumuli. In these
      cases, the maximum width is not the bideltoid width, but the bitrochiteric width.
      Intermediate and deep liposuction was performed only over the posterior and
      external aspect, because superficial and circumferential liposuction may result
      in multiple irregularities on the anterior and internal surfaces. During the same
      medical act, fat-graft injection in deltoid region was performed to balance the
      contour of the scapular belt. With this technique, an aesthetically balanced zone
      was obtained. The results for 48 patients treated with arm liposuction and fat
      graft injection in the deltoid area were very satisfying.

PMID- 16283578
TI  - Sterile fluid collections in acute pancreatitis: catheter drainage versus simple
      aspiration.
AB  - PURPOSE: To compare the clinical outcome of needle aspiration versus percutaneous
      catheter drainage of sterile fluid collections in patients with acute
      pancreatitis. METHODS: We reviewed the clinical and imaging data of patients with
      acute pancreatic fluid collections from 1998 to 2003. Referral for fluid sampling
      was based on elevated white blood cell count and fevers. Those patients with
      culture-negative drainages or needle aspirations were included in the study.
      Fifteen patients had aspiration of 10-20 ml fluid only (group A) and 22 patients
      had catheter placement for chronic evacuation of fluid (group C). We excluded
      patients with grossly purulent collections and chronic pseudocysts. We also
      recorded the number of sinograms and catheter changes and duration of catheter
      drainage. The CT severity index, Ranson scores, and maximum diameter of abdominal
      fluid collections were calculated for all patients at presentation. The total
      length of hospital stay (LOS), length of hospital stay after the drainage or
      aspiration procedure (LOS-P), and conversions to percutaneous and/or surgical
      drainage were recorded as well as survival. RESULTS: The CT severity index and
      acute Ransom scores were not different between the two groups (p = 0.15 and p =
      0.6, respectively). When 3 crossover patients from group A to group C were
      accounted for, the duration of hospitalization did not differ significantly, with
      a mean LOS and LOS-P of 33.8 days and 27.9 days in group A and 41.5 days and 27.6
      days in group C, respectively (p = 0.57 and 0.98, respectively). The 60-day
      mortality was 2 of 15 (13%) in group A and 2 of 22 (9.1%) in group C. Kaplan
      Meier survival curves for the two groups were not significantly different (p =
      0.3). Surgical or percutaneous conversions occurred significantly more often in
      group A (7/15, 47%) than surgical conversions in group C (4/22, 18%) (p = 0.03).
      Patients undergoing catheter drainage required an average of 2.2 sinograms/tube
      changes and kept catheters in for an average of 52 days. Aspirates turned culture
      positive in 13 of 22 patients (59%) who had chronic catheterization. In group A,
      3 of the 7 patients converted to percutaneous or surgical drainage had infected
      fluid at the time of conversion (total positive culture rate in group A 3/15 or
      20%). CONCLUSIONS: There is no apparent clinical benefit for catheter drainage of
      sterile fluid collections arising in acute pancreatitis as the length of hospital
      stay and mortality were similar between patients undergoing aspiration versus
      catheter drainage. However, almost half of patients treated with simple
      aspiration will require surgical or percutaneous drainage at some point.
      Disadvantages of chronic catheter drainage include a greater than 50% rate of
      bacterial colonization and the need for multiple sinograms and tube changes over
      an average duration of about 2 months.

PMID- 16283580
TI  - Laparoscopy-assisted distal gastrectomy for early gastric cancer: experience with
      111 consecutive patients.
AB  - BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) is gaining wider
      acceptance for the treatment of early gastric cancer. However, firm evidence
      supporting its safety and usefulness is scant, and no study has compared the
      outcomes of various procedures for LADG. We examined the surgical outcomes of
      LADG performed using different methods for lymph node dissection. METHODS:
      Between September 1998 and January 2005, we performed LADG in 111 patients with
      early gastric cancer. In the 55 patients treated initially, group 2 lymph node
      dissection was performed through a small, 7-cm-long incision (minilaparotomy). In
      43 of these patients, hand-assisted laparoscopic surgery (HALS) was done. In the
      56 patients treated more recently, lymph node dissection was performed
      laparoscopically. In 31 of these patients, the celiac branches of the vagus nerve
      were preserved. Clinical outcomes of these procedures were compared. RESULTS: In
      the first 55 patients, HALS significantly shortened the operation time (277 vs
      243 min, p < 0.05). In the latter 56 patients, LADG with preservation of the
      celiac branches of the vagus nerve was associated with a longer operation time
      (283 vs 228 min, p < 0.01) and higher blood loss (150 vs 92 g, p < 0.05) than
      with LADG without celiac branch preservation. There were no differences among the
      various operative procedures in postoperative course, including the length of the
      postoperative hospital stay or the rate of complications. CONCLUSIONS: LADG is a
      safe and technically feasible procedure for the treatment of early gastric
      cancer. Laparoscopic lymph node dissection provided a good visual field and was
      easier to perform and required less time when the celiac branches of the vagus
      nerve were not preserved, with no negative effect on outcome.

PMID- 16283581
TI  - Biphasic and dually coordinated expression of the genes encoding major shell
      matrix proteins in the pearl oyster Pinctada fucata.
AB  - Regional expression patterns of shell matrix protein genes of Pinctada fucata
      were investigated using real-time quantitative polymerase chain reaction (PCR)
      and in situ hybridization. Six shell matrix proteins examined in this study
      indicated a distinct biphasic pattern of expression, falling into one of the
      following three groups: (1) expressed only in the more dorsal region of the
      mantle (MSI60 and N16); (2) expressed only in the more ventral region (MSI31,
      Prismalin-14, and Aspein); and (3) expressed in both regions (nacrein). The
      ubiquity of the last protein probably reflects its general role as a carbonate
      producing enzyme, while the other groups are interpreted as corresponding to the
      distinction between the two varieties of shell layers, the aragonitic nacreous
      layer and the calcitic prismatic layer. In addition, the constituent genes of
      each of these two groups indicated similar levels of relative expression among
      different sites even among different individuals, suggesting that the genes of
      each group share a single upstream regulatory factor, respectively, and that
      these genes are expressed in a dually coordinated fashion.

PMID- 16283582
TI  - Functional magnetic resonance imaging of the kidney using macromolecular contrast
      agents.
AB  - BACKGROUND: Functional magnetic resonance (MR) imaging of the kidney relies on
      low-molecular-weight contrast agents. These agents are glomerular filtration
      markers and are neither secreted nor reabsorbed by the tubules but are filtered
      at the glomerulus. Low-molecular-weight contrast agents provide limited
      functional information. A new generation of macromolecular magnetic contrast
      agents is under development for MR angiography. These agents may provide
      additional renal functional information not provided by low-molecular-weight
      agents. METHODS: We review the use of macromolecular contrast agents such as
      gadolinium-bound albumin (Gd-albumin), gadolinium-bound dendrimer (Gd-dendrimer),
      and ultrasmall particles of iron oxide (USPIO) in specific renal parenchymal
      diseases. These data are largely derived from animal studies because many of
      these agents have not been extensively deployed in human populations. RESULTS:
      Different specific uses have been documented for macromolecular contrast agents.
      Gd-albumin appears to detect the source of proteinuria and localize the site of
      recurrent proteinuria after transplantation. Gd-dendrimer uptake reflects damage
      to the proximal straight tubule in the outer medulla. USPIO agents demonstrate
      sites of inflammatory changes within the kidney. CONCLUSIONS: Although not yet in
      widespread clinical use, macromolecular MR contrast agents may play a role in the
      evaluation of functional diseases of the kidneys.

PMID- 16283583
TI  - Ischemia and infarction of the small bowel and colon: spectrum of imaging
      findings.

PMID- 16283584
TI  - Portal venous tumor thrombus associated with hepatic metastasis of renal cell
      carcinoma: case report.
AB  - We report a case of liver metastasis of renal cell carcinoma with portal venous
      tumor thrombus. Abdominal computed tomographic images showed a large hepatic mass
      that enhanced slightly during arterial phase. Multiple hypoattenuating lesions
      were seen in the intrahepatic portal venous branches and were traced directly
      from the mass. The histologic specimen confirmed metastatic liver tumor of renal
      cell carcinoma with portal venous tumor thrombus.

PMID- 16283586
TI  - Conformational changes of 3,5,3'-triiodo L-thyronine induced by interactions with
      phospholipid: physiological speculations.
AB  - The conformational changes of 3,5,3'-triiodo L-thyronine induced by interaction
      with phospholipids were analyzed by Raman spectroscopy. The spectra were
      interpreted in terms of two conformers of this hormone in equilibrium in the
      lipid medium, depending on the orientation of the 3'-iodine with respect to the
      ring alpha. Theoretical geometry optimizations on both conformers in vacuo and in
      different solvents, together with the respective calculated energies support the
      experimental results. The presence of only one iodine atom in the phenolic ring
      allows assumption of a higher flexibility of 3,5,3'-triiodo L-thyronine and a
      better accommodation into the lipid medium compared to 3,5,3',5'-tetraiodo L
      thyronine. The possible physiological implications of structural differences that
      appear in membrane models between 3,5,3'-triiodo L-thyronine and 3,5,3',5'
      tetraiodo L-thyronine are discussed.

PMID- 16283585
TI  - Signaling pathways in the biphasic effect of ANG II on Na+/H+ exchanger in T84
      cells.
AB  - The effect of ANG II on pH(i), [Ca(2+)](i) and cell volume was investigated in
      T84 cells, a cell line originated from colon epithelium, using the probes BCECF
      AM, Fluo 4-AM and acridine orange, respectively. The recovery rate of pH(i) via
      the Na(+)/H(+) exchanger was examined in the first 2 min following the
      acidification of pH(i) with a NH(4)Cl pulse. In the control situation, the pH(i)
      recovery rate was 0.118 +/- 0.001 (n = 52) pH units/min and ANG II (10(-12) M or
      10(-9) M) increased this value (by 106% or 32%, respectively) but ANG II (10(-7)
      M) decreased it to 47%. The control [Ca(2+)](i) was 99 +/- 4 (n = 45) nM and ANG
      II increased this value in a dose-dependent manner. The ANG II effects on cell
      volume were minor and late and should not interfere in the measurements of pH(i)
      recovery and [Ca(2+)](i). To document the signaling pathways in the hormonal
      effects we used: Staurosporine (a PKC inhibitor), W13 (a calcium-dependent
      calmodulin antagonist), H89 (a PKA inhibitor) or Econazole (an inhibitor of
      cytochrome P450 epoxygenase). Our results indicate that the biphasic effect of
      ANG II on Na(+)/H(+) exchanger is a cAMP-independent mechanism and is the result
      of: 1) stimulation of the exchanger by PKC signaling pathway activation (at 10(
      12) - 10(-7) M ANG II) and by increases of [Ca(2+)](i) in the lower range (at 10(
      12) M ANG II) and 2) inhibition of the exchanger at high [Ca(2+)](i) levels (at
      10(-9) - 10(-7) M ANG II) through cytochrome P450 epoxygenase-dependent
      metabolites of the arachidonic acid signaling pathway.

PMID- 16283587
TI  - Genistein inhibits the activity of kv1.3 potassium channels in human T
      lymphocytes.
AB  - In the present study, the whole-cell patch-clamp technique was applied to follow
      the inhibitory effect of genistein--a tyrosine kinase inhibitor and a natural
      anticancer agent--on the activity of voltage-gated potassium channels Kv1.3
      expressed in human T lymphocytes (TL). Obtained data provide evidence that
      genistein application in the concentration range of 1-80 microM reversibly
      decreased the whole-cell potassium currents in TL in a concentration-dependent
      manner to about 0.23 of the control value. The half-blocking concentration range
      of genistein was from 10 to 40 microM. The current inhibition was correlated in
      time with a significant decrease of the current activation rate. The steady-state
      activation of the currents was unchanged upon application of genistein, as was
      the inactivation rate. The inhibitory effect of genistein on the current
      amplitude and activation kinetics was voltage-independent. The current inhibition
      was not changed significantly in the presence of 1 mM of sodium orthovanadate, a
      tyrosine phosphatase inhibitor. Application of daidzein, an inactive genistein
      analogue, did not affect significantly either the current amplitudes or the
      activation kinetics. Possible mechanisms of the observed phenomena and their
      significance for genistein-induced inhibition of cancer cell proliferation are
      discussed.

PMID- 16283588
TI  - Non-stationary fluctuation analysis of macroscopic gap junction channel records.
AB  - Non-stationary fluctuation analysis was applied to macroscopic records of
      junctional currents arising from homotypic Cx37 and Cx43 gap junction channels
      expressed in RIN cells. The data were analyzed by a modification of existing
      analytical methods that takes endemic uncoupling into account. The results are
      consistent with both channels having open probabilities ranging from 0.7 to near
      unity for low transjunctional voltages. The analysis also yielded estimates of
      single-channel conductances for the two channel types similar to those seen in
      single-channel recordings. The results presented here show that fluctuation
      analysis can be used to extract single-channel gap junctional conductances from
      macroscopic double whole-cell recordings. These results also constitute
      empirically determined estimates of the open probability that are not model
      dependent.

PMID- 16283589
TI  - Mechanism of the Na,K-ATPase inhibition by MCS derivatives.
AB  - The previously reported class of potent inorganic inhibitors of Na,K-ATPase,
      named MCS factors, was shown to inhibit not only Na,K-ATPase but several P-type
      ATPases with high potency in the sub-micromolar range. These MCS factors were
      found to bind to the intracellular side of the Na, K-ATPase. The inhibition is
      not competitive with ouabain binding, thus excluding its role as cardiac-steroid
      like inhibitor of the Na,K-ATPase. The mechanism of inhibition of Na,K-ATPase was
      investigated with the fluorescent styryl dye RH421, a dye known to report changes
      of local electric fields in the membrane dielectric. MCS factors interact with
      the Na,K-ATPase in the E(1) conformation of the ion pump and induce a
      conformational rearrangement that causes a change of the equilibrium dissociation
      constant for one of the first two intracellular cation binding sites. The MCS
      inhibited state was found to have bound one cation (H(+), Na(+) or K(+)) in one
      of the two unspecific binding sites, and at high Na(+) concentrations another
      Na(+) ion was bound to the highly Na(+)-selective ion-binding site.

PMID- 16283590
TI  - Regulation of the slow vacuolar channel by luminal potassium: role of surface
      charge.
AB  - Voltage-dependent activation of slow vacuolar (SV) channels has been studied on
      isolated patches from red beet (Beta vulgaris L.) vacuoles. Isoosmotic variation
      of vacuolar K(+) from 10 to 400 mM in Ca(2+)-free solutions at the vacuolar side
      shifted the SV channel activation threshold to more positive voltages. The effect
      of K(+) could be mimicked by additions of choline or N-methyl D-glucamine and
      could be explained by unspecific screening of the negative surface charge.
      Fitting the dependence of voltage shift on K(+) concentration to the Gouy-Chapman
      model yields a surface charge density of 0.36 +/- 0.05 e(-)/nm(2). Negative
      surface potential also tended to increase the local concentration of permeable
      ions (K(+)), resulting in anomalously high single-channel conductance,
      approximately 200 pS in 10 mM KCl. An increase of ionic strength due to addition
      of impermeable cations greatly reduced the unitary conductance. Large positive
      shift of the SV channel voltage dependence, caused by physiological (0.5 mM) free
      vacuolar Ca(2+), was partly ameliorated by increasing luminal K(+). We
      interpreted these results as follows: K(+)induced a reduction of surface
      potential, hence i) causing a positive shift of the voltage dependence and ii) a
      dilution of Ca(2+) in the membrane vicinity, thus reducing the inhibitory effect
      of vacuolar Ca(2+) and causing a negative shift of the SV channel voltage
      dependence, with a sum of the two shifts being negative.

PMID- 16283591
TI  - Localizing extracellular signal-regulated kinase (ERK) in pharmacological
      preconditioning's trigger pathway.
AB  - Acetylcholine (ACh) and opioid receptor agonists trigger the preconditioned
      phenotype through sequential activation of the epidermal growth factor (EGF)
      receptor, phosphatidylinositol 3-kinase (PI3-K), Akt, and nitric oxide synthase
      (NOS), and opening of mitochondrial (mito) K(ATP) channels with the generation of
      reactive oxygen species (ROS). Although extracellular signal-regulated kinase
      (ERK) has recently been reported to be part of this pathway, its location has not
      been determined. To address this issue, we administered a 5-min pulse of ACh (550
      microM) prior to 30 min of ischemia in isolated rabbit hearts. It reduced
      infarction from 30.4 +/- 2.2% of the risk zone in control hearts to 12.3 +/- 2.8%
      and co-administration of the MEK, and, therefore, downstream ERK inhibitor U0126
      abolished protection (29.1 +/- 4.6% infarction) con.rming ERK's involvement.
      MitoK(ATP) opening was monitored in adult rabbit cardiomyocytes by measuring ROS
      production with MitoTracker Red. ROS production was increased by each of three G
      protein-coupled agonists: ACh (250 microM), bradykinin (BK) (500 nM), and the
      delta-opioid agonist DADLE (20 nM). Co-incubation with the MEK inhibitors U0126
      (500 nM) or PD 98059 (10 microM) blocked the increased ROS production seen with
      all three agonists. Direct activation of its receptor by EGF increased ROS
      production and PD 98059 blocked that increase, thus placing ERK downstream of the
      EGF receptor. Desferoxamine (DFO) which opens mitoK(ATP) through direct
      activation of NOS also increased ROS. PD 98059 could not block DFO-induced ROS
      production, placing ERK upstream of NOS. In isolated hearts, ACh caused
      phosphorylation of both Akt and ERK. U0126 blocked phosphorylation of ERK but not
      of Akt. The PI3-K inhibitor wortmannin blocked both. Together these data indicate
      that ERK is located between Akt and NOS.

PMID- 16283592
TI  - Myocardial preconditioning and remote renal preconditioning--identifying a
      protective factor using proteomic methods?
AB  - It is still unknown whether remote ischemic preconditioning is mediated by a
      humoral or a neurogenic mechanism from the preconditioning to the preconditioned
      tissue. The purpose of the following study was to identify a possible humoral
      trigger of ischemic myocardial preconditioning and remote renal preconditioning.
      Open chest rats were subjected to a coronary artery occlusion period of 45 min
      followed by 2 h of reperfusion (Control animals; n = 6). The coronary
      preconditioned group (IPC, n = 6) was subjected to a preceding preconditioning
      period of 5 min coronary artery occlusion followed by 5 min of reperfusion,
      repeated three times. The renal preconditioned group (IPR, n = 6) was subjected
      to a preceding renal artery occlusion period of 10 min followed by 20 min of
      reperfusion. Area at risk (AAR) and infarcted area (IA) were determined at the
      end of each protocol. Blood samples were taken at the end of the preconditioning
      protocols from parallel experiments for proteomic analysis using two-dimensional
      gel electrophoresis (2-DE), matrix assisted laser desorption and ionization-time
      of flight-mass spectrometry (MALDI-TOF-MS), and liquid chromatography
      electrospray ionization-tandem mass spectrometry (nanoLC-ESI-MS/MS). IA/AAR was
      87.8 +/- 10.7% in the control group. IPC and IPR significantly reduced IA/AAR
      (58.2 +/- 9.3% and 56.9 +/- 9.0%, p < 0.001). Proteomic analyses detected four
      protein spots which were either up- (n = 3) or down-regulated in the
      preconditioned groups vs. the control group. The three up-regulated protein spots
      were identified as albumin fragments, whereas the down-regulated spot was
      identified as liver regeneration-related protein (LRRG03). Interestingly, albumin
      modification by brief ischemia has been recently shown and evaluated for the
      clinical diagnosis of sublethal myocardial ischemia. However, no differentially
      abundant proteins which possess a known signaling function could be found. Hence,
      though there is a differential protein expression in blood following IPC and IPR,
      our data are not in favor of a humoral mediator of remote preconditioning with a
      molecular weight of more than 8 kDa. Our results rather suggest either a
      neurogenic pathway or a mediator smaller than 8 kDa.

PMID- 16283593
TI  - Adenylyl cyclase type V deletion increases basal left ventricular function and
      reduces left ventricular contractile responsiveness to beta-adrenergic
      stimulation.
AB  - We tested the hypothesis that deletion of adenylyl cyclase type V (AC(V)) would
      be associated with decreased left ventricular (LV) contractile function and
      responsiveness to beta-adrenergic receptor (betaAR) stimulation. Absence of
      cardiac AC(V) expression was confirmed by RT-PCR and immunoblotting in AC(V)
      deleted mice (AC(V) (-/-)). Compared to sibling mice with normal amounts of AC(V)
      (CON), basal and water-soluble forskolin derivative NKH477-stimulated cAMP
      production was reduced in both LV homogenates and in isolated cardiac myocytes.
      Basal LV +dP/dt (isolated perfused hearts) was increased (CON: 3,649 +/- 247
      mmHg/s; AC(V) (-/-): 4,625 +/- 350 mmHg/s; p = 0.035, n = 10), but the potency of
      dobutamine on LV +dP/dt was decreased by AC(V) deletion (log EC(50): CON: -6.83
      +/- 0.14 M; AC(V) (-/-): -5.99 +/- 0.15 M; p = 0.0007, n = 10). The initial rates
      of ATP-dependent sarcoplasmic reticulum calcium uptake, assessed in LV
      homogenates, showed that AC(V) deletion increased SERCA2a affinity for Ca(2+)
      (log EC(50): CON: -5.94 +/- 0.03 M; AC(V) (-/-): -6.09 +/- 0.02 M; p = 0.001, n =
      8). AC(V) deletion is also associated with increased phospholamban
      phosphorylation, decreased type 1 protein phosphatase catalytic subunit content
      and activity, and reduced cardiac Galphas protein content. In conclusion, AC(V)
      deletion has a favorable effect on basal LV function despite reduced cAMP levels.
      Increased SERCA2a affinity for Ca(2+) and increased phospholamban phosphorylation
      are contributing factors. However, AC(V) deletion is associated with reduced LV
      contractile responsiveness to betaAR stimulation, an effect that is associated
      with reduced Galphas protein content and reduced cAMP generating capacity in
      cardiac myocytes.

PMID- 16283594
TI  - Suppression of physiological cardiomyocyte proliferation in the rat pup after
      neonatal glucocorticosteroid treatment.
AB  - BACKGROUND: Glucocorticosteroids (mostly dexamethasone) are widely used to
      prevent chronic lung disease in premature infants. Neonatal rats treated with
      dexamethasone have been shown to have reduced cardiac mass and cardiomyocyte
      hypertrophy, suggesting a lower number of cardiomyocytes at adult age, and a
      severely reduced life expectancy. In the present study we tested the hypothesis
      that a lower number of cardiomyocytes in later life is caused by a reduced
      cardiomyocyte proliferation and/or by early cell death (apoptosis). METHODS AND
      RESULTS: Rat pups received dexamethasone or saline control on day 1, 2 and 3 and
      were sacrificed at day 0, 2, 4, 7 and 21. The cardiomyocytes of dexamethasone
      treated pups showed a reduced proliferation as indicated by a lower mitotic index
      and reduced number of Ki-67 positive cardiomyocytes on day 2 and 4 as compared to
      day 0 and day 7 and also as compared to the age-matched saline pups. On day 7 and
      day 21 the mitotic index was not different between groups. From day 2 onward up
      to day 21 dexamethasone treated pups showed a lower number of cardiomyocytes. The
      cardiomyocytes showed no signs (<<1%) of apoptosis (Caspase-3 and cleaved-PARP)
      in any group. CONCLUSION: The temporary suppression of cardiomyocyte hyperplasia
      found in dexamethasone treated pups eventually leads to a reduced number and
      hypertrophy of cardiomyocytes during adult life.

PMID- 16283595
TI  - Masked facial affect priming is associated with therapy response in clinical
      depression.
AB  - In the present study, automatic processing of facial affect in clinical
      depression was investigated in the course of an inpatient treatment program.
      Patients suffering from clinical depression (n = 20) and healthy controls (n =
      21) completed the facial affective priming task developed by Murphy and Zajonc
      (1993) twice, about 7 weeks apart. Subjects were instructed to evaluate neutral
      Chinese ideographs primed by masked displays of sad, happy, and neutral facial
      affect, including a no-prime condition. In the course of treatment, patients
      recovered significantly. In acutely depressed patients, no priming based on
      emotional faces could be found compared to neutral faces at time 1. However,
      compared to the no-prime condition, negative evaluation shifts elicited by
      neutral and sad faces were found which were significantly correlated with symptom
      severity. Patients with persisting high levels of depression after therapy judged
      ideographs more negatively in all three facial prime conditions at time 1. We
      conclude that clinically depressed patients are characterized by automatic
      processing biases for facial affect. An enhanced sensitivity for sad facial
      expressions and a negatively biased automatic processing of neutral and happy
      facial affect appears to be associated with depression persistence.

PMID- 16283596
TI  - Age-period-cohort analysis of Swiss suicide data, 1881-2000.
AB  - At the end of the 19(th) century, male suicide rates in Switzerland were as high
      as the respective rates in recent decades, whereas female suicide rates were
      distinctly lower. An age-period-cohort analysis was performed to provide more
      information about the gender-specific changes over the last century. Suicide
      mortality has been reported in Switzerland since 1876 when the standardised
      registration of mortality data began. The analysed data cover the period 1881
      2000. The statistical analyses were based on log-linear models and data
      aggregated by 10-year age-intervals and 10-year period intervals. The results
      indicate similar age and period effects in males and females. The estimates
      representing age-specific risk increase steadily with age, with intermediate
      plateaus in the 20s and the 50s. The period-specific estimates follow the
      economic cycles. The birth cohort effects are stronger in males and weaker in
      females. In the males' estimates, there is a peak in cohorts born around 1840 and
      a low in cohorts born some 60-100 years later. The estimates increased again in
      generations born after World War II. In females, the birth cohort estimates are
      low in cohorts born in the first half of the 19(th) century and increase until
      the first half of the 20(th) century. Birth cohort effects remain an intriguing
      topic in epidemiology of suicide. A better understanding of birth cohort effects
      might open new doors to suicide prevention.

PMID- 16283597
TI  - Fine motor function and neuropsychological deficits in individuals at risk for
      schizophrenia.
AB  - Deficits in fine motor function and neuropsychological performance have been
      described as risk factors for schizophrenia. In the Basel FEPSY study
      (Fruherkennung von Psychosen; English: Early Detection of Psychosis) individuals
      at risk for psychosis were identified in a screening procedure (Riecher-Rossler
      et al. 2005). As a part of the multilevel assessment, 40 individuals at risk for
      psychosis and 42 healthy controls matched for age, sex and handedness were
      investigated with a fine motor function test battery and a neuropsychological
      test battery. Individuals at risk showed lower performances in all subtests of
      the fine motor function tests, predominantly in dexterity and velocity
      (wrist/fingers and arm/hand). In the neuropsychological test battery, individuals
      at risk performed less well compared to healthy controls regarding sustained
      attention, working memory and perseveration. The combined evaluation of the two
      test batteries (neuropsychological and fine motor function) separates the two
      groups into individuals at risk and healthy controls better than each test
      battery alone. A multilevel approach might therefore be a valuable contribution
      to detecting beginning schizophrenia.

PMID- 16283598
TI  - Postoperative chylous ascites in a neonate treated successfully with octreotide:
      bile sludge and cholestasis.
AB  - We report a case of postoperative chylous ascites after surgical repair of
      congenital diaphragmatic hernia (CDH) in a full-term neonate. Treatment with
      subcutaneously administered octreotide resulted in rapid resolution of chylous
      effusion. Octreotide treatment had transient side effects, with bile sludge and
      cholestasis.

PMID- 16283599
TI  - Detecting small for gestational age infants: the development of a population
      based reference for Washington state.
AB  - Small for gestational age (SGA) infants are at increased risk for morbidity and
      mortality. The objective of this study was to develop a birthweight for
      gestational age reference that more accurately represents the Washington state
      population, focusing on SGA. Washington state birth certificate files of
      singleton births in 1989 to 1998 were used to develop the 3rd, 10th, 50th, and
      90th percentiles of birthweight for gestational age for males and females. The
      Washington state 10th percentile curve most closely approximates a nationally
      representative reference, whereas an earlier but widely used California-based
      reference had the lowest centiles across gestational age with few exceptions.
      Using the Washington reference, 8.4% of Washington births would be classified as
      SGA (<10th percentile), compared with 5.5 and 7.4% using the California and
      national reference, respectively. The new reference may be helpful in assessing
      local regional data, and other areas with similar demographics, and provide more
      relevant clinical guidance.

PMID- 16283600
TI  - Neonatal hepatoblastoma: two cases posing a diagnostic dilemma, with a review of
      the literature.
AB  - Hepatoblastoma accounts for less than 1% of all pediatric malignancies. However,
      it remains the most common malignant tumor of the liver in newborns. Less than
      10% of hepatoblastoma cases are diagnosed in the neonatal period. The diagnosis
      can be very difficult due to the wide spectrum of presentation and differences in
      the size of the lesion at the time of detection either antenatally or during an
      infant's neonatal course. In this review, we describe the current investigations
      used to establish the diagnosis of congenital hepatoblastoma and the role of a
      nuclear red cell scan as an additional strategy in the evaluation of this
      malignant condition. The report uses two cases of neonatal hepatoblastoma to
      highlight both the clinical and pathologic findings, and the problems encountered
      in the evaluation of this disorder.

PMID- 16283601
TI  - In utero nicotine exposure and fetal growth inhibition among twins.
AB  - We examined the impact of cigarette smoking on fetal growth among twins by
      analyzing matched twin live births in the United States from 1995 through 1998.
      The outcomes of interest were low and very low birthweight, preterm and very
      preterm birth, and small for gestational age. Out of a total of 163,901 mothers,
      19,234 reported active smoking during pregnancy (11.7%). Twins born to smokers
      weighed an average of 182 g less than their counterparts born to nonsmokers
      (p<0.001). The risk for fetal growth inhibition was greater among twins of
      smokers: low birthweight (adjusted odds ratio [OR], 1.84; 95% confidence Interval
      [CI], 1.79 to 1.89), very low birthweight (OR, 1.27; 95% CI, 1.21 to 1.32),
      preterm (OR, 1.3; 95% CI, 1.09 to 1.16), very preterm (OR, 1.18; 95% CI, 1.13 to
      1.23), and small for gestational age (OR, 1.91; 95% CI, 1.84 to 1.98). In
      conclusion, prenatal smoking significantly inhibits fetal growth among twins, and
      small for gestational age appeared more affected than shortened gestation.

PMID- 16283602
TI  - Umbilical cord unbound free fatty acid concentration and low apgar score.
AB  - Increased levels of unbound Free Fatty acid (FFAu) have been found in adults
      undergoing coronary angioplasty as a result of acute hypoxia-ischemia. We
      hypohesized that infants suffering from a 1-minute Apgar score of less than 5
      will demonstrate elevated FFAu levels in the cord blood. One hundred ninety-nine
      infants between 25 and 41 weeks gestational age were enrolled in the study.
      Infants with an Apgar score of less than 5 at 1 minute served as the study group.
      Blood samples were collected from the umbilical cord and serum FFAu levels were
      measured with the fluorescent probe acrylodan-derivatized intestinal fatty acid
      binding protein. The low Apgar score group (n=32, birthweight 3153+/-780 g,
      gestational age 37.9+/-3.1 weeks) and normal Apgar score group (n=167,
      birthweight 3067+/-847 g, gestational age 37.5+/-3.5 weeks) were significantly
      different with respect to Apgar score at 1 minute (3.0+/-1.2 versus 8.4+/-1.1),
      Apgar score at 5 minutes (6.9+/-versus 8.9+/-0.5), cord pH (7.16+/-0.12 versus
      7.28+/-0.07), and in the frequency of meconium passage (40.6% versus 14.9%). Cord
      FFAu levels were 4.4+/-1.7 versus 3.2+/-1.2 nM (p<0.001), respectively. Cord FFAu
      correlated inversely with Apgar score at 1 minute (r=-0.31, p<0.05) and with cord
      pH (r=-0.12, p<0.05), but not with birthweight or gestational age. In infants
      with low 1-minute Apgar scores, cord free fatty acid levels were significantly
      elevated compared with those from controls.

PMID- 16283603
TI  - Recurrent antepartum compression of a single artery double nuchal cord
      necessitating emergency cesarean delivery.
AB  - Fetuses with a single umbilical artery are considered at increased risk for
      chromosomal and structural abnormalities, and increased adverse perinatal
      outcome. A young nulliparous patient was followed with weekly nonstress testing
      due to well-controlled gestational diabetes, a single umbilical artery, and a
      double nuchal cord. At 31 weeks gestation, following the occurrence of a severe
      prolonged variable deceleration of the fetal heart rate the patient was
      hospitalized for close fetal surveillance with consideration that the
      deceleration may represent recurring intermittent compression of the single
      umbilical artery. Continuous fetal monitoring depicted recurrent severe variable
      decelerations of the fetal heart rate. Thirty-six hours after admission,
      prolonged fetal bradycardia to 60 bpm necessitated emergency cesarean delivery of
      a nonhypoxic nonacidotic fetus, which subsequently did well. This case suggests
      that fetuses with a single umbilical artery nuchal cord(s) may be at increased
      risk of significant umbilical cord compression.

PMID- 16283604
TI  - Antenatal glucocorticoid treatment decreases mortality and chronic lung disease
      in survivors among 23- to 28-week gestational age preterm infants.
AB  - The purpose of this study was to analyze the influence of antenatal
      glucocorticoid therapy (AGT) on mortality and chronic lung disease (CLD) in
      surviving preterm infants 23 to 28 weeks gestational age (WGA). This was a
      multicenter, prospective, observational study. A total of 2448 infants 23 to 28
      WGA were born in 2002 to 2003; 27.7% did not receive AGT, 18.8% were exposed to
      partial AGT, and 53.5% were exposed to complete AGT. A total of 883 died and
      22.9% of 1537 survivors were affected by CLD. Unadjusted univariate analysis
      showed AGT was associated with a reduction in mortality (p<0.001), either with
      partial or complete AGT courses, and also with a reduction in CLD in survivors
      (p<0.001), but only with complete AGT courses. In logistic regression analysis
      adjusted for confounding factors and a propensity score for AGT, AGT was
      significant and independently associated with a reduction of mortality, but only
      for complete AGT course (odds ratio [OR], 0.64; 95% confidence interval [CI],
      0.47 to 0.87; p=0.004), and with a decrease in CLD if a complete AGT course was
      administered (OR, 0.63; 95% CI, 0.45 to 0.89; p=0.009). A complete course of AGT
      in 23 to 28 WGA pregnancies is associated with decreased rates of neonatal
      mortality and CLD disease in surviving infants.

PMID- 16283605
TI  - The effect of early recombinant erythropoietin and enteral iron supplementation
      on blood transfusion in preterm infants.
AB  - Premature infants<1500 g were randomly assigned to study and control groups. In
      the study group, 42 premature infants received recombinant human erythropoietin
      (r-Hu EPO) 750 U/kg per week subcutaneously from day 5 to 40 and enteral iron
      supplementation of 2 to 6 mg/kg/d beginning on day 14 provided that they were
      receiving at least 50% energy intake orally. In the control group, 51 infants
      received the same dose of enteral iron supplementation beginning at the end of
      the fourth week. At the end of a 12-week monitoring period, r-Hu EPO combined
      with early enteral iron reduced transfusion needs only in the subgroup<1000 g. r
      Hu EPO and early iron treatment had no effect on the development of severe
      retinopathy of prematurity, intraventricular hemorrhage, necrotizing
      enterocolitis, and bronchopulmonary dysplasia. We suggest that r-Hu EPO combined
      with early enteral iron is both effective and safe in infants<1000 g.

PMID- 16283606
TI  - Kaposi's sarcoma and pregnancy.

PMID- 16283608
TI  - [How specific are neuropsychological functions in autism?].

PMID- 16283609
TI  - [Neuropsychology of autistic disorders].
AB  - Autistic disorders are pervasive developmental disorders, which are characterised
      by social, communicative and stereotyped, repetitive behaviour patterns. The
      onset of these disorders is in early childhood and they are most likely of
      biological origin. A review of neuropsychological questions and results is
      presented. Special features are found with regard to intelligence, attention,
      memory, speech, executive functions, theory of mind and central coherence. The
      different neuropsychological features are explained in terms of an integrated
      model which takes into account the elementary functions, systems of functioning
      and the underlying theoretical concepts. Autistic disorders can be understood as
      an integration deficit of these different functions.

PMID- 16283610
TI  - [Social exclusion of the mentally ill -- a critical review and outlook of
      community psychiatry at the beginning of the 21st century].
AB  - The social implications and disabilities of long-term mental disorders have been
      well described and are known for a long time. The classical paradigm of social
      psychiatry postulating that dehospitalization automatically generates social
      integration has proven to be wrong. Along that line the view that living in the
      community supported by different services aiming at integration has also failed
      to be successful. Without explicitly labelling it: community-based psychiatry has
      yielded a psychiatry-based community. It never served the majority of the non
      chronically mentally ill with disordered social skills who also need specific
      support or are as well bound for unemployment and social disadvantages. Without
      doubt, the progress made by community psychiatry in the past was eminently linked
      to the ideology and implementation of deinstitutionalization. Defining and
      dealing with social exclusion means a turning point for social and community
      psychiatry - a new paradigm that could generate a different view upon
      therapeutical outcomes and the way that therapy and rehabilitation have to be
      organised and implemented. Especially the example of vocational rehabilitation
      could mark a stepping stone by initiating further investigations and progress for
      new approaches in community support. Supported employment programmes have shown
      the superiority of "place and train" instead of first train in institutions or
      services and then place on the spot. Thus a so-called inclusion therapy could
      arise that takes place "in vivo et actu" and near to the individual's real world
      of tasks and demands. Progress in any part of multidimensional therapy is
      legitimized only by empirical validation of functional outcome and social
      inclusion measures. Such an evaluation of complex programmes taking social
      inclusion into account is sophisticated but seems to be necessary in the field of
      general psychiatric therapies as well as for the legitimation of financial
      resources needed. Foreseeing the perspective of social psychiatry a next
      substantial step could be the identification of social and functional outcome
      variables.

PMID- 16283611
TI  - [Which schizophrenic patients improve under work therapy, which ones don't?].
AB  - This investigation is part of a multicenter study, where only small effects and
      no superiority compared to creative ergotherapy was found for four weeks of
      inpatient work therapy. The criteria were three scales of the Osnabruck-Working
      Capabilities Profile (O-AFP) assessing basic learning ability, social
      communication ability and adaptation at the work place. The goal of this
      investigation is to identify subgroups of patients within the work therapy group,
      which differ in their course of ability level during the intervention. Three
      subgroups were identified for each scale. Subgroups with improvements comprise 24
      % (learning ability) and 15 % (social communication) of the sample. Adaptation
      level decreases in a group of 9 % of the patients. The remaining clusters show
      constancy of abilities at different levels. Comparison of the clusters with
      neurocognitive, symptom and motivational variables shows that for learning
      ability mainly neurocognitive variables yield salient differences, whereas for
      social communication abilities, symptoms and motivation, together with a specific
      aspect of memory, seem to be characteristic. Only positive symptoms are related
      to adaptation. Also, there are hints for variables that specifically characterize
      patients with improvement of ability level. The discussion deals with issues of
      assessment and prognosis in rehabilitation, contributions to the neurocognitive
      theory of schizophrenia and to the development of person-centered interventions.

PMID- 16283612
TI  - [Valproate sustained release in the treatment of epilepsy].
AB  - In an observational study under routine clinical setting data after
      administration of once daily evening dosing of valproate sustained release
      minitablets were recorded in 359 patients with epilepsy aged between 12 and 86
      years. Patients were either newly treated with valproate sustained release
      minitablets (N = 58) or switched from conventional valproate (N = 124) or from
      sustained release valproate (N = 138) to the once daily evening dosing. In 39
      patients other antiepileptic drugs were replaced. At the end of the 7-week
      observational period most patients (65.4 %) received a daily dose of 10 to less
      than 18 mg/kg body weight followed by 17.4 % receiving doses in the
      therapeutically recommended range of 18 - 24 mg/kg. 8.6 % and 7.4 % of patients
      received more than 24 mg/kg or less than 10 mg/kg body weight, respectively. As
      expected, in both groups with valproate pre-treatment the mean morning valproate
      plasma levels increased by approximately 10 microg/ml after switch to once
      evening dosing with sustained release minitablets. The mean seizure frequency
      decreased from 2.1 to 0.5 in the 318 patients with data before the beginning and
      at the end of the investigation. At the final examination 137 patients (62.3 %)
      were seizure free, and further 60 patients (27.3 %) experienced a seizure
      reduction of more than 50 % (responder) of those 220 patients who experienced
      seizures in the last 7 weeks before the study. The efficacy and tolerability was
      rated in more than 95 % of the cases by the patient and the investigator as good
      or very good. The compliance/acceptance of the valproate sustained release
      minitablets was rated as good or very good in almost all patients. These results
      confirm the excellent benefit-risk ratio of the valproate sustained release
      minitablets and underline the importance of a simple compliance-improving dose
      regimen for effective seizure control.

PMID- 16283613
TI  - [Psychiatric and neuropsychological signs and symptoms in patients with fabry
      disease: literature review].
AB  - Fabry Disease (FD) is an X-linked lysosomal storage disorder (prevalence about 1
      : 100 000) caused by a genetic defect associated with a lack of alpha
      galactosidase A (alpha-GAL) enzyme activity. As a consequence, neutral
      glycosphingolipides can not be cleaved and metabolized, and accumulate in
      lysosomes of several tissues, particularly in vascular endothelium and smooth
      muscle cells. The most prominent symptoms comprise pain attacks and
      acroparesthesia, angiokeratoma, corneal opacity, renal and cardiac dysfunction,
      hypo- and anhidrosis, gastrointestinal symptoms, and cerebrovascular dysfunction
      with vertigo, headache, and cerebral ischemia. Characteristic symptoms of FD can
      occur in male and female patients with the same prevalence, while females with FD
      seem to be less severely affected. The course of untreated illness is progressive
      with considerable interindividual variability. Since 2001 two enzyme replacement
      therapies are approved which can possibly stop the disease progress and alleviate
      symptoms. The very few reports and clinical observations have shown that a very
      high proportion of FD patients develop neuropsychiatric symptoms. However,
      accurate data are lacking. Although the pathophysiologic mechanisms are quite
      unknown, it is surmised that sphingolipid deposits in the endothelium of small
      cerebral vessels lead to regional cerebral ischemia accompanied by
      neuropsychiatric symptoms and deficits. Furthermore, patients with FD are
      chronically distressed by pain attacks and additional somatic and psychological
      impairment. Frequently, pain attacks are triggered by psychosocial stress. The
      high interindividual variability can, thus, also be interpreted on the basis of
      existing stress and coping models. The present paper will review the presently
      available psychiatric and neuropsychological findings in FD and will discuss
      difficulties associated with classification and differential diagnosis of
      psychiatric disorders occurring in patients with FD.

PMID- 16283614
TI  - [Diagnostics and treatment of the generalized anxiety syndrome (GAS)].

PMID- 16283615
TI  - Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald
      Criteria".
AB  - New diagnostic criteria for multiple sclerosis integrating magnetic resonance
      image assessment with clinical and other paraclinical methods were introduced in
      2001. The "McDonald Criteria" have been extensively assessed and used since 2001.
      New evidence and consensus now strengthen the role of these criteria in the
      multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in
      time, to clarify the use of spinal cord lesions, and to simplify diagnosis of
      primary progressive disease. The 2005 Revisions to the McDonald Diagnostic
      Criteria for MS should simplify and speed diagnosis, whereas maintaining adequate
      sensitivity and specificity.

PMID- 16283616
TI  - Evolution of Parkinson's disease during 4 years of bilateral deep brain
      stimulation of the subthalamic nucleus.
AB  - Patients with advanced Parkinson's disease (PD) and motor complications can
      obtain significant symptom improvement by deep brain stimulation (DBS) of the
      subthalamic nucleus (STN). Very little is published, however, about long-term
      effect and disease evolution during DBS. We performed a 4-year prospective study
      of the first 22 consecutive patients treated with STN DBS. The patients were
      evaluated with Unified Parkinson's Disease Rating Scale Part II to VI and a
      patient diary concerning on-off periods and dyskinesia. Patients were scored
      before surgery on medication and off medication for 10 to 12 hours and in four
      conditions 1 and 4 years after surgery: off medication+/-stimulation and on
      medication+/-stimulation. In advanced PD, a significant reduction of dyskinesia
      and off periods was present 4 years (90%/67%) after the operation. Total motor
      function on stimulation alone improved 55% at 4 years, compared with baseline and
      activities of daily living (42%). On stimulation, significant worsening of axial
      symptoms and speech was present from 1 to 4 years. To evaluate disease evolution,
      motor symptoms were assessed off stimulation and medication for 12 hours and were
      found not to worsen compared with baseline, which is remarkable in an otherwise
      progressive disorder. Five patients developed dementia. Severe adverse events
      were not observed.

PMID- 16283617
TI  - Differentiation of rhabdomyosarcoma cell lines using retinoic acid.
AB  - BACKGROUND: Rhabdomyosarcoma (RMS) is the most frequent sporadic soft tissue
      sarcoma of childhood and adolescence. The overall 5-year survival rate for
      patients with RMS is 70% with the use of surgery, radiation, and chemotherapy.
      Novel therapeutic approaches are necessary to improve on these outcomes
      particularly among the more aggressive alveolar RMS (ARMS) and late stages of
      disease, where 5-year survival is less than 20%. Retinoids have been successfully
      used in the treatment of acute promyelocytic leukemia (APML) and neuroblastoma.
      PURPOSE: However, analysis of retinoids as a differentiating agent for RMS has
      been incomplete. This work examined the ability of retinoic acid (RA) to promote
      differentiation of RMS cell lines by examining the expression of myogenic
      proteins in five RMS cell lines in response to All-trans Retinoic Acid (ATRA) or
      9-cis retinoic acid (CRA). RESULTS: Analysis of growth curves indicates that both
      retinoids suppress cell growth of Rh4 and Rh28. RD cells only responded to-CRA
      whereas Rh30 and Rh18 did not respond. Following treatment with ATRA FACS
      analysis showed an altered cell cycle with the same pattern as the growth curves.
      ATRA altered cellular morphology of two cell lines, Rh4 and Rh28, and induced
      Troponin T expression in these cells suggesting a differentiating effect.
      CONCLUSIONS: These studies suggest that retinoids are effective inducers of
      growth arrest and differentiation in some RMS cell lines, and offer a basis for
      further in vivo testing in mice of ATRA as a potential approach to ARMS
      treatment.

PMID- 16283618
TI  - Amplified, lost, and fused genes in 11q23-25 amplicon in acute myeloid leukemia,
      an array-CGH study.
AB  - Gene amplifications occur rarely in hematologic neoplasms. We characterized two
      cases of acute myeloid leukemia (AML) with marker chromosomes and 11q23-25
      amplicons. Case 1 was a 14-year-old male with an additional ring of chromosome 11
      material as the sole karyotypic abnormality, as determined by G-banding and
      multicolor fluorescence in situ hybridization. Standard comparative genomic
      hybridization (CGH) showed amplification in 11q23-qter. However, the MLL gene, in
      11q23, was not amplified by FISH. Case 2 was a 38-year-old male with the G
      banding karyotype 51,XY,+8,+19,+3mar and with 11q22-qter amplification by
      standard CGH. This patient also had the MLL-LARG fusion gene. We used microarray
      based CGH (array-CGH) to characterize the amplicons. In case 1, the amplified
      region in 11q24.3-25 (5.5 Mb) was continuous, and MLL was not amplified, as
      expected. In case 2, the amplicon was divided into two distinct parts, in 11q23.3
      (1.2 Mb) and in 11q23.3-25 (13.3 Mb). It contained a loss ( approximately 1 Mb)
      in 11q23.3, and the amplicon breakpoint was in the middle of MLL. Although the
      amplicon size varied, the patients had a common amplified region in 11q24-25 that
      comprised 14 genes. Expression microarray of case 1 revealed that three of these
      genes, FLI1, NFRKB, and SNX19, were also overexpressed. The results indicate that
      the 11q24-q25 region may harbor new candidate oncogenes. In addition, the complex
      amplicon of case 2 suggests some intriguing chromosomal mechanisms.

PMID- 16283619
TI  - Post-transplant lymphoproliferative disorder subtypes correlate with different
      recurring chromosomal abnormalities.
AB  - Although cytogenetic analysis advanced the understanding of the pathogenesis of
      primary non-Hodgkin lymphoma and led to improved clinical management, there have
      been no large cytogenetic studies of post-transplant lymphoproliferative disorder
      (PTLD). We examined the karyotypes of 36 PTLD cases and correlated them with
      clinical, laboratory, and pathologic findings. The cases included 2 early
      lesions, 13 polymorphic PTLDs, and 21 monomorphic PTLDs (18 B-cell and 3 T-cell
      proliferations). Cytogenetic abnormalities were identified in 72% of monomorphic
      B-cell PTLDs and in all T-cell PTLDs, but in only 15% of polymorphic PTLDs and in
      no early lesions. The most frequent clonal abnormalities in monomorphic PTLD were
      trisomies 9 and/or 11 (5 cases), followed by rearrangements of 8q24.1 (4 cases),
      3q27 (2 cases), and 14q32 (2 cases). MYC rearrangement (8q24.1) and T-cell
      associated chromosomal abnormalities correlated with poor outcome and short
      survival. PTLD with trisomy 9 and/or 11 developed early after transplant,
      presenting as Epstein-Barr virus-positive large B-cell lymphoma with prolonged
      survival.

PMID- 16283620
TI  - Disruption of BRCA1 function results in telomere lengthening and increased
      anaphase bridge formation in immortalized cell lines.
AB  - BRCA1 is a tumor suppressor that functions in controlling cell growth and
      maintaining genomic stability. BRCA1 has also been implicated in telomere
      maintenance through its ability to regulate the transcription of hTERT, the
      catalytic subunit of telomerase, resulting in telomere shortening, and to
      colocalize with the telomere-binding protein TRF1. The high incidence of
      nonreciprocal translocations in tumors arising from BRCA1 mutation carriers and
      Brca1-null mice also raises the possibility that BRCA1 plays a role in telomere
      protection. To date, however, the consequences for telomere status of disrupting
      BRCA1 have not been reported. To examine the role of BRCA1 in telomere
      regulation, we have expressed a dominant-negative mutant of BRCA1 (trBRCA1),
      known to disrupt multiple functions of BRCA1, in telomerase-positive mammary
      epithelial cells (SVCT) and telomerase-negative ALT cells (GM847). In SVCT cells,
      expression of trBRCA1 resulted in an increased incidence of anaphase bridges and
      in an increase in telomere length, but no change in telomerase activity. In GM847
      cells, trBRCA1 also increased anaphase bridge formation but did not induce any
      change in telomere length. BRCA1 colocalized with TRF2 in telomerase-positive
      cells and with a small subset of ALT-associated PML bodies (APBs) in ALT cells.
      Together, these results raise the possibility that BRCA1 could play a role in
      telomere protection and suggest a potential mechanism for one of the phenotypes
      of BRCA1-deficient cells.

PMID- 16283621
TI  - Spectrum of single- and multiexon NF1 copy number changes in a cohort of 1,100
      unselected NF1 patients.
AB  - Neurofibromatosis type 1 (NF1), the most common tumor-predisposing disorder in
      humans, is caused by defects in the NF1 tumor-suppressor gene. Comprehensive
      mutation analysis applying RNA-based techniques complemented with FISH analysis
      achieves mutation detection rates of approximately 95% in NF1 patients. The
      majority of mutations are minor lesions, and approximately 5% are total gene
      deletions. We found 13 single- and/or multiexon deletions/duplications out of
      1,050 detected mutations using our RNA-based approach in a cohort of 1,100 NF1
      patients and confirmed these changes using multiplex ligation-dependent probe
      amplification (MLPA). With MLPA, we found another 12 novel multiexon
      deletion/duplications in 55 NF1 patients for whom analysis with multiple assays
      had not revealed a NF1 mutation, including 50 previously analyzed
      comprehensively. The extent of the 22 deletions and 3 duplications varied
      greatly, and there was no clustering of breakpoints. We also evaluated the
      sensitivity of MLPA in identifying deletions in a mosaic state. Furthermore, we
      tested whether the MLPA P122 NF1 area assay could distinguish between type I
      deletions, with breakpoints in low-copy repeats (NF1-LCRs), and type II
      deletions, caused by aberrant recombination between the JJAZ gene and its
      pseudogene. Our study showed that intragenic deletions and/or duplications
      represent only approximately 2% of all NF1 mutations. Although MLPA did not
      substantially increase the mutation detection rate in NF1 patients, it was a
      useful first step in a comprehensive mutation analysis scheme to quickly pinpoint
      patients with single- or multiexon deletions/duplications as well as patients
      with a total gene deletion who will not need full sequencing of the complete
      coding region.

PMID- 16283622
TI  - Genetic evidence for a maternal effect locus controlling genomic imprinting and
      growth.
AB  - Crosses between two species of deer mouse (Peromyscus) yield dramatic parent-of
      origin effects. Female P. maniculatus (BW) crossed with male P. polionotus (PO)
      produce animals smaller than either parent. PO females crossed with BW males
      yield lethal overgrowth that has been associated with loss-of-imprinting (LOI).
      Previously, we mapped two loci influencing fetal growth. These two loci, however,
      do not account for the LOI, nor for the dysmorphic phenotypes. Here we report
      that maternal genetic background strongly influences the LOI. Analyses of crosses
      wherein maternal genetic background is varied suggest that this effect is likely
      due to the action of a small number of loci. We have termed these putative loci
      Meil. Estimation of Meil loci number was confounded by skewed allelic ratios in
      the intercross line employed. We show that the Meil loci are not identical to any
      of the DNA methyltransferases shown to be involved in regulation of genomic
      imprinting.

PMID- 16283623
TI  - Specific dynamic and noninvasive labeling of pancreatic beta cells in reporter
      mice.
AB  - Noninvasive detection of differentiated cells is increasingly demanded for
      accurate and reliable assessments of both in vitro and in vivo experimental
      systems. Here we present an efficient, innovative approach for imaging the beta
      cells of the pancreatic islets of Langerhans. The main physiologic function of
      beta cells is glucose-stimulated insulin secretion. This function is facilitated
      through the synthesis and storage of insulin in secretory vesicles of beta cells,
      which then release their contents when beta cells are exposed to hyperglycemic
      conditions. To visualize beta cells in vivo in the mouse, we used targeted
      mutagenesis techniques to construct a modified insulin II (InsII) gene allele,
      InsII(EGFP), that expresses a proinsulin-EGFP (enhanced green fluorescent
      protein) fusion peptide. The EGFP portion of this fusion is entirely within the C
      peptide portion of the proinsulin peptide. This fusion protein is processed in
      beta cells to insulin and EGFP-tagged C peptide, which are stored together in
      cytoplasmic secretory vesicles. The large amount of vesicular EGFP-tagged C
      peptide is evident as a characteristic robust and specific fluorescence pattern
      in the beta cells of InsII(EGFP) mice. This innovative method of visualizing beta
      cells will be a useful tool in the study of both beta cell physiology and the
      development of the endocrine cells of the pancreas.

PMID- 16283624
TI  - Conditional LoxP-flanked glucosylceramide synthase allele controlling
      glycosphingolipid synthesis.
AB  - Glycosphingolipids are organizational building blocks of plasma membranes that
      participate in key cellular functions, such as signaling and cell-to-cell
      interactions. Glucosylceramide synthase--encoded by the Ugcg gene--controls the
      first committed step in the major pathway of glycosphingolipid synthesis. Global
      disruption of the Ugcg gene in mice is lethal during gastrulation. We have now
      established a Ugcg allele flanked by loxP sites (floxed). When cre recombinase
      was expressed in the nervous system under control of the nestin promoter, the
      floxed gene underwent recombination, resulting in a substantial reduction of Ugcg
      expression and of glycosphingolipid ganglio-series levels. The mice deficient in
      Ugcg expression in the nervous system show a striking loss of Purkinje cells and
      abnormal neurologic behavior. The floxed Ugcg allele will facilitate analysis of
      the function of glycosphingolipids in development, physiology, and in diseases
      such as diabetes and cancer.

PMID- 16283625
TI  - Generation of conditional alleles of the murine Iron Regulatory Protein (IRP)-1
      and -2 genes.
AB  - Central aspects of cellular iron metabolism are controlled by IRP1 and IRP2,
      which are ubiquitously expressed in mouse organs and cells. Total and
      constitutive deficiency of both IRPs causes embryonic lethality in the mouse. To
      bypass the early lethality and to study organ-specific and/or temporal functions
      of IRP1 and/or IRP2 we generated Irp1 and Irp2 conditional alleles. We used mouse
      lines where a betaGeo gene trap construct was inserted into the second intron of
      the Irp1 and the Irp2 gene, generating hypomorphic alleles by interrupting the
      corresponding open reading frame near the amino-termini. The gene trap cassettes
      are flanked by Frt sites and were co-inserted with LoxP sites flanking exon 3.
      Flp-mediated removal of the gene trap construct generates floxed alleles with
      wildtype functions. For both Irp genes, Cre-assisted deletion of exon 3 generates
      complete null alleles that, in the case of IRP2, are associated with altered body
      iron distribution and compromised hematopoiesis. If not removed, the gene trap
      construct causes partially penetrant embryonic lethality unrelated to IRP
      deficiency when inserted within the Irp1 but not the Irp2 locus. We discuss the
      implications for functional genomics in the mouse.

PMID- 16283626
TI  - Generation of a conditional allele of the B-myb gene.
AB  - B-Myb is an essential transcription factor involved in control of the cell cycle
      and the regulation of tissue-specific gene expression in a wide range of cell
      types. Loss of both alleles results in early embryonic lethality at E4.5-6.5. To
      address the function of B-Myb in later stages of embryogenesis and in specific
      adult tissues, a floxed B-myb allele (B-mybF) was generated. Cre-mediated
      deletion in vivo was demonstrated by breeding with a transgenic GATA-Cre mouse
      line. An intermediate allele produced in the creation of the floxed allele, in
      which the PGK-neo(R) cassette is present in intron 3 (B-myb(loxneo)), was deduced
      to be a weak hypomorph based on the later embryonic death of homozygotes compared
      to B-myb(-/-) embryos. To demonstrate the efficiency and possible consequences of
      B-myb inactivation, we performed conditional deletion in cultured MEFs and
      observed decreased growth that correlated with aberrant nuclear DNA replication.

PMID- 16283627
TI  - Adenotonsillectomy for obstructive sleep apnea in children with Prader-Willi
      syndrome.
AB  - The aim of our study was to evaluate the efficacy of adenotonsillectomy for the
      treatment of obstructive sleep apnea syndrome (OSA) in pediatric patients with
      Prader-Willi syndrome (PWS), and to describe the postoperative complications.
      Five patients (4 males; median age, 4.4 years; range, 1.6-14.2 years) were
      studied. All patients underwent an overnight cardiorespiratory sleep study. All
      patients had adenotonsillar hypertrophy (ATH), and two were also obese. The
      preoperative obstructive apnea/hypopnea index (AHI; median and range) was 12.2
      (9.0-19.9) events/hr; the mean oxygen saturation was 95 (79-96)%; the nadir
      oxygen saturation was 71 (58-78)%; and the oxygen desaturation index (ODI) was
      15.8 (11.4-35.9) events/hr. Preoperatively, patients were classified as having
      moderate to severe OSA. A second sleep study, performed 16 (3-43) months after
      adenotonsillectomy, showed a significant decrease in AHI (P = 0.009) and ODI (P =
      0.009). Mean and nadir oxygen saturation did not differ significantly postsurgery
      (P = 0.188, P = 0.073, respectively). Four out of five children showed at least
      one postoperative complication. Difficult awakening from anesthesia, hemorrhages,
      and respiratory complications requiring reintubation and/or supplemental oxygen
      administration were observed. In conclusion, patients with PWS and OSA who
      underwent adenotonsillectomy showed a significant decrease in AHI and number of
      oxygen desaturations.

PMID- 16283628
TI  - Prevalence of asthma among Qatari schoolchildren: International Study of Asthma
      and Allergies in Childhood, Qatar.
AB  - The aim of the present study is to determine the prevalence of asthma and
      allergic diseases among schoolchildren aged 6-14 years in the State of Qatar,
      based on a questionnaire designed by the International Study of Asthma and
      Allergy in Childhood (ISAAC). A cross-sectional study of 3,283 school children
      living in both urban and rural areas (average age, 9.03 +/- 1.99 years; 52.3%
      boys and 47.7% girls) was conducted between February 2003-February 2004. The
      population sample had a high prevalence of diagnosed asthma (19.8%), allergic
      rhinitis (30.5%), eczema (22.5%), and chest infection (11.9%). The frequency of
      asthma, allergic rhinitis, and eczema among parents reflected the same pattern as
      seen in their children. Overall, males had more asthma, allergic rhinitis, and
      chest infections than females. In general, the prevalence rate of asthma and
      allergic rhinitis decreased with age. The prevalence rate of asthma was
      significantly higher in mothers (11.8%) than in fathers (9.0%), but the frequency
      of allergic rhinitis symptoms was comparable (mothers, 18.5%; fathers, 17.5%).
      The prevalence rate of asthma (19.8%) in Qatari schoolchildren is very close to
      that in the neighboring Gulf country, Oman (20.7%), and higher than in some
      developing countries. Genetic factors related to the high rates of consanguinity
      may play an important role in the high prevalence rates noted in the Qatari
      population, but changes in lifestyle and environmental factors cannot be
      discounted as possible causes of the high prevalence noted in this study.

PMID- 16283629
TI  - Second primary rhabdomyosarcoma of bone after osteosarcoma.

PMID- 16283630
TI  - Hepatoblastoma in a child with neurofibromatosis type I.
AB  - A major hallmark of NF1 is the development of benign tumors, including peripheral
      neurofibromas, plexiform neurofibromas, gliomas of the optic tract, other low
      grade gliomas, and pheochromocytomas. Hepatoblastoma have not been previously
      reported in patients with neurofibromatosis type 1. We present a case of a 9
      month-old boy diagnosed with both hepatoblastoma and neurofibromatosis type 1.
      Hepatoblastoma occurs in association with several well-described cancer
      predisposition syndromes, including familial adenomatous polyposis, Beckwith
      Wiedemann syndrome, Li-Fraumeni syndrome, trisomy 18, and glycogen storage
      disease type I. This paper describes a case of hepatoblastoma diagnosed in
      association with neurofibromatosis type 1.

PMID- 16283631
TI  - Photoablation of inner limiting membrane and inner retinal layers using the
      Erbium:YAG-laser: an in vitro study.
AB  - BACKGROUND AND OBJECTIVES: To explore the potential of Er:YAG-laser irradiation
      for precise and tractionless retinal tissue and inner limiting membrane ablation.
      MATERIALS AND METHODS: We used free-running Er:YAG-laser irradiation (lambda =
      2.94 microm) transmitted either through a 10 cm long low-OH-quartz fiber or a 2 m
      long sapphire fiber that produced a more homogenous light distribution at the
      fiber tip. Retinal ablation in porcine retinal explants was performed under air
      or perfluorodecaline (PFD). Ablation depth was evaluated by optical coherence
      tomography (OCT) and from histologic sections. RESULTS: A radiant exposure of 5.0
      J/cm(2) delivered through a low-OH-quartz fiber and PFD caused a complete
      transsection of the neurosensory retina. Radiant exposures between 3.5 and 2.0
      J/cm(2) resulted in marked variations of ablation depth and adjacent thermal
      damage. By contrast, laser pulses of 4.0 and 3.0 J/cm(2) transmitted through the
      sapphire fiber produced more homogenous defect patterns and less thermal damage.
      Close to the ablation threshold, with 1.0-2.0 J/cm(2), ablation was limited to a
      10-20 microm thin layer of the neural retina. CONCLUSIONS: We achieved in vitro
      ablation of inner retinal layers, but could not produce selective and
      reproducible ILM removal.

PMID- 16283632
TI  - 5-Fluorouracil interferes with actin organization, stress fiber formation and
      cell migration in corneal endothelial cells during wound repair along the natural
      basement membrane.
AB  - Corneal endothelial cells respond to a circular freeze wound by undergoing actin
      cytoskeletal reorganization that is mainly characterized by the disappearance of
      circumferential microfilament bundles (CMBs) and the subsequent appearance of
      distinct stress fibers. This cytoskeletal rearrangement is associated with
      changes in cell shape as migrating cells lose their polyhedral appearance, spread
      out, and assume a stellate morphology with cell processes extending outward into
      the injured area. We report here that in the presence of low concentrations (0.01
      0.l mM) of the anti-metabolite 5-fluorouracil (5-FU), characteristic actin
      organization becomes disrupted and migrating cells do not display elongated
      processes typical of control tissues and translocation into the injury zone is
      retarded, but not inhibited. Rhodamine phalloidin staining revealed no evidence
      of stress fiber formation. A higher concentration of 5-FU (1.0 mM) not only
      prevented formation of discernible stress fibers but also resulted in a more
      restricted cell movement during wound repair. That this was not a cytotoxic
      effect was demonstrated by transferring tissues back into standard medium
      allowing endothelia to reinitiate migration and undergo complete wound healing by
      72 h post-transfer. Overnight incubation of endothelia in 4 muM phallacidin
      resulted in limited CMB disruption the extent of which was dependent on the 5-FU
      concentration. The effects of 5-FU on the actin cytoskeleton are reversible and
      by 24 h after placing treated endothelia into medium without 5-FU, actin begins
      to become re-established and by 48 h microfilament patterns in the tissue
      resemble those of non-treated endothelia. Similarly, when non-injured tissues are
      cultured in the presence of 5-FU for 24 h, subsequently injured and returned to
      standard medium, they exhibit no stress fibers when observed at 24 h post
      wounding. However, by 48 h post-injury these cells now display stress fibers and
      extend processes into the wound area. Biochemical studies on isolated muscle
      actin demonstrated that actin polymerization is unaffected in the presence of
      either 0.01 or 1 mM 5-FU as determined by the F-actin sedimentation and falling
      ball viscosity techniques. Thus, the mechanism(s) by which 5-FU exerts its
      actions on the actin cytoskeleton appears to be one of an indirect nature.

PMID- 16283634
TI  - The tabatiere anatomique.
AB  - There is scant detailed information regarding the tabatiere anatomique
      (anatomical snuff box) in the literature. The authors dissected this area in 15
      adult cadavers (30 sides) and made measurements and observations of this region.
      We found that the average mean width and length of this geometric area was 4 cm
      and 6 cm, respectively. Although the dimensions of the tabatiere anatomique
      tended to be larger among male specimens this trend did not reach statistical
      significance (P > 0.05). There was no statistical difference between left and
      right sides. The majority (70%) of specimens was noted to have connections
      between the cephalic vein and the vena comitantes of the radial artery within the
      tabatiere anatomique. Five specimens were noted to have a muscular branch to the
      abductor pollicis brevis muscle arising from the dorsalis pollicis artery in the
      tabatiere anatomique. The dorsalis pollicis artery was found to originate in the
      tabatiere anatomique in all specimens. One right-sided specimen was noted to have
      an intraosseous branch of the radial artery that entered the styloid process of
      the radius. A well-formed collection of fat was noted between the styloid process
      and base of the first metacarpal in all specimens. This fat pad completely
      covered the radial artery in the majority of specimens and had loose connections
      to both the first and second dorsal compartments. The branches of the superficial
      branch of the radial nerve always originated distal to the tendon of the EPB
      muscle. These data may prove useful to the surgeon or clinician who operates or
      examines this interesting anatomical area.

PMID- 16283633
TI  - Injections of osteoprotegerin and PMA delay tooth eruption.
AB  - Tooth eruption requires alveolar bone resorption that is regulated by the dental
      follicle. This is reflected by the fact that failures of eruption often can be
      traced to either osteoclast deficiencies or to dental follicle abnormalities. To
      achieve maximal osteoclastogenesis and subsequent alveolar bone resorption for
      eruption, we have hypothesized that a reduction in gene expression of
      osteoprotegerin (OPG) in the follicle of the first mandibular molar of the rat at
      Day 3 is needed. To determine if OPG affects eruption, postnatal rats were
      injected with varying concentrations of OPG from Days 1-9 postnatally. Such
      studies indicated that the eruption time of the first mandibular molar was
      significantly delayed by 1 day or more as a result of OPG injection. Injection of
      phorbolmyristate acetate (PMA), an activator of protein kinase C (PKC) that in
      turn upregulates OPG expression, also delayed eruption by 1 day. PMA was only
      injected from Days 1-4 such that PKC-alpha would be increased and activated.
      Previous studies had shown that PKC-alpha gene expression is downregulated at the
      time (Day 3) that OPG expression is downregulated. In this study, using reverse
      transcription polymerase chain reaction techniques to examine OPG gene expression
      showed that PMA injection increased OPG gene expression in the dental follicle at
      Day 3 as compared to the controls. Thus, either injecting OPG or enhancing its
      expression in the follicle at Day 3 by injecting PMA delays the time of tooth
      eruption. Consequently, regulation of OPG production by the dental follicle
      likely affects the alveolar bone resorption needed for tooth eruption.

PMID- 16283635
TI  - Ectopic supernumerary tooth on the inferior nasal concha.
AB  - Variations regarding the location of an ectopic tooth in the human nasal cavity,
      although rare, are documented in the literature, but presence of an ectopic tooth
      on the inferior nasal concha (INC) has not been reported. We observed an
      anomalous tooth projecting from the posterior margin of the right INC in two
      adult female skulls. A small quadrangular tooth projected beyond the posterior
      margin of the hard palate in one of the skulls and a medium sized conical tooth
      was observed in the other skull. The affected INC in both skulls were located
      more inferiorly compared to the opposite side and were in close approximation
      with the hard palate. No similar findings were noted on the contralateral side
      nor were there any associated congenital or iatrogenic deformity. The
      phylogenetic, ontogenetic, and clinical importance of this variant is described.
      Knowledge of such an anomaly is of paramount importance to
      otorhinolaryngologists, reconstructive and dental surgeons, and radiologists for
      identification of such rarities encountered during invasive or non-invasive
      procedures.

PMID- 16283637
TI  - Bony anomaly of Meckel's cave.
AB  - This study describes the seemingly rare occurrence of bone formation within the
      proximal superior aspect of Meckel's cave thus forming a bony foramen for the
      proximal trigeminal nerve to traverse. The anatomy of Meckel's cave is reviewed
      and the clinical potential for nerve compression from this bony anomaly
      discussed.

PMID- 16283636
TI  - Complete ossification of the human falx cerebri.
AB  - During the routine dissection of the head and neck of an adult male cadaver
      complete ossification of the falx cerebri was noted. Anomalous ossification was
      not found in any other dural component or other parts of the body. The brain
      appeared grossly normal. Histological sections showed normal ossification
      processes involving the falx cerebri. In addition, rare scattered deposits of
      metastatic poorly differentiated carcinoma within the trabecular spaces were
      seen. Reports of isolated islands of ossification involving primarily the most
      anterior part of the falx cerebri in man are found in the literature. Our case
      report represents to our knowledge, the first report of complete ossification of
      this dural partition. Whether this is simply an anomalous configuration or due to
      the few metastatic cells found within this region remains unclear.

PMID- 16283638
TI  - Preliminary study on digitized nasal and temporal bone anatomy.
AB  - The purpose of this study was to explore a feasible method for the reconstruction
      of the nasal and temporal bone structures of the Chinese virtual human project
      and provide a more accurate and facilitated way view them three-dimensionally
      (3D). The 3-D Slicer software was used to reconstruct the anatomic structures of
      the human nose and temporal bone. Segmentation and extraction of the contours of
      the ROI (region of interest) in each single slice were conducted and the
      processed volume data was transferred into the 3-D Slicer. After resegmentation,
      a set of labeled maps of the ROI were produced. Based on these maps, the 3D
      surface models of the tissues of interest were constructed. Four groups of
      paranasal sinuses, nasal septa, middle and inferior turbinates, temporal bones,
      tympanic cavities, mastoid air cells, sigmoid sinuses, and internal carotid
      arteries were reconstructed successfully. These models show spatial relationships
      and orientation between them. The results show that the 3-D Slicer may be used
      for the 3D visualization of parts of anatomic structures in the nose and temporal
      bone based on the first Chinese virtual human data, and thus, can facilitate the
      observation and understanding of the anatomic structures in this area.

PMID- 16283639
TI  - Formal procedural skills training using a fresh frozen cadaver model: a pilot
      study.
AB  - Graduating medical students are expected to be proficient in a number of
      procedural skills. A structured curriculum is infrequently available. In
      addition, the use of a mannequin tends to be unrealistic and students continue to
      have some anxiety when performing procedures on patients. This pilot study was
      designed to demonstrate the utility of a fresh frozen cadaver model in practicing
      procedural skills as compared to mannequins. Seven third-year students carried
      out a number of basic procedural skills using a mannequin model and a fresh
      frozen cadaver. We surveyed the students after they had carried out the
      procedures on the different models with regards to ease of procedure, the sense
      of realism and their success rate. The pilot course improved the overall
      confidence of the students in performing basic skills. In addition, despite the
      fact that the mannequin was somewhat easier to perform a number of procedures on,
      the fresh frozen cadaver was a more realistic model and the preferred model for
      practicing the skills. The fresh frozen cadaver is a feasible and valid
      instructional tool for training procedural skills and has the advantage of being
      more realistic than a typical mannequin model.

PMID- 16283641
TI  - Light alters nociceptive effects of magnetic field shielding.
AB  - Orientation and nociception (pain sensitivity) are affected by exposure to
      geomagnetic or low frequency (<1,000 Hz) magnetic fields of approximately the
      earth's field strength, i.e., 50 microT. However, these effects are often
      dependent on the simultaneous presence of visible light. Recently, it was shown
      that nociception was affected in mice acutely exposed to an electromagnetic
      shielded environment in the dark (<0.05 W/m(2)) during the mid-light phase of the
      diurnal cycle. Here, we report for the first time that if mice are exposed to
      magnetic shielding in the presence of visible light (0.6 W/m(2), 400-750 nm) that
      most of the effects of shielding are eliminated. This simple experimental
      protocol may be useful in investigating the role that light plays in the
      detection of ambient electromagnetic fields.

PMID- 16283642
TI  - Dynamics of the ion cyclotron resonance effect on amino acids adsorbed at the
      interfaces.
AB  - In this study we show a reproduction of the Zhadin experiment, which consists of
      the transient increase of the electrolytic current flow across an aqueous
      solution of L-arginine and L-glutamic acid induced by a proper low frequency
      alternating magnetic field superimposed to a static magnetic field of higher
      strength. We have identified the mechanisms that were at the origin of the so-far
      poor reproducibility of the above effect: the state of polarization of the
      electrode turned out to be a key parameter. The electrochemical investigation of
      the system shows that the observed phenomenon involves the transitory activation
      of the anode due to ion cyclotron frequency effect, followed again by anode
      passivation due to the adsorption of amino acid and its oxidation products. The
      likely occurrence of similar ion cyclotron resonance (ICR) phenomena at
      biological membranes, the implications on ion circulation in living matter, and
      the consequent biological impact of environmental magnetic fields are eventually
      discussed.

PMID- 16283643
TI  - Preparation of amino-acid-type selective isotope labeling of protein expressed in
      Pichia pastoris.
AB  - We report the culture conditions for successful amino-acid-type selective (AATS)
      isotope labeling of protein expressed in Pichia pastoris (P. pastoris).
      Rhodostomin (Rho), a six disulfide-bonded protein expressed in P. pastoris with
      the correct fold, was used to optimize the culture conditions. The concentrations
      of [alpha-15N] selective amino acid, nonlabeled amino acids, and ammonium
      chloride, as well as induction time, were optimized to avoid scrambling and to
      increase the incorporation rate and protein yield. The optimized protocol was
      successfully applied to produce AATS isotope-labeled Rho. The labeling of [alpha
      15N]Cys has a 50% incorporation rate, and all 12 cysteine resonances were
      observed in HSQC spectrum. The labeling of [alpha-15N]Leu, -Lys, and -Met amino
      acids has an incorporation rate greater than 65%, and the expected number of
      resonances in the HSQC spectra were observed. In contrast, the labeling of [alpha
      15N]Asp and -Gly amino acids has a low incorporation rate and the scrambling
      problem. In addition, the culture condition was successfully applied to label
      dendroaspin (Den), a four disulfide-bonded protein expressed in P. pastoris.
      Therefore, the described condition should be generally applicable to other
      proteins produced in the P. pastoris expression system. This is the first report
      to present a protocol for AATS isotope labeling of protein expressed in P.
      pastoris for NMR study.

PMID- 16283645
TI  - Descriptive anatomy of the insertion of the biceps femoris muscle.
AB  - The biceps femoris is the most lateral component of the so-called hamstring
      muscles. Classically, this muscle's insertion into the head of the fibula has
      been described but further details of its anatomy have not been universally
      appreciated. Additional insertions into the crural fascia and tibia have been
      described. We dissected 56 cadavers paying especially close attention to the
      insertion of the biceps femoris muscle. The tendon of this muscle was found to
      have both medial and lateral slips each with an anterior and posterior component.
      Further, we found an attachment not only into the lateral condyle of the femur
      but also the popliteus tendon and arcuate popliteal ligament. Our study has found
      that the tendon of insertion of the biceps femoris muscle is more complex than
      described previously and suggests that this tendon may be far more important in
      knee stability based on the multiple attachment sites found. We hypothesize that
      there may be a synergistic effect between the biceps femoris and the popliteus
      muscles based on our findings of an additional attachment of the biceps femoris
      tendon into the popliteus tendon. This study provides new detailed nomenclature
      for the description of the tendon of insertion of the biceps femoris muscle and
      indicates that the current description of the insertion of the tendon of the
      biceps femoris muscle should be revised. The clinician must have a thorough
      understanding of this anatomy before correct therapeutic maneuvers can be
      implemented.

PMID- 16283644
TI  - Ethnic-, gender-, and age-related differences in femorotibial angle, femoral
      antetorsion, and tibiofibular torsion: cross-sectional study among healthy
      Japanese and Australian Caucasians.
AB  - The current study was conducted to examine ethnic, gender, and age-related
      differences in femorotibial angle (FTA), femoral antetorsion and tibiofibular
      torsion. Healthy Japanese (n = 120) and Australian Caucasian (n = 82) subjects
      were examined using a series of clinically reliable methods for measuring FTA and
      torsion of the lower limb. Subjects between 18-29 years of age were categorized
      as younger, 30-59 years as middle age, and 60 or more as older age. Three-way
      analysis of variance was utilized for data analysis. The Japanese subjects had
      significantly greater FTA (more varus) than the Australian subjects (P < 0.001).
      Femoral antetorsion in the Japanese subjects was significantly smaller in middle
      and older age groups than younger group (P < 0.05), but did not differ between
      the age groups in the Australian subjects. Further, tibiofibular torsion in
      female subjects was significantly greater in younger and middle age groups than
      the older age group (P < 0.01), but was not different between different age
      groups in males. The results suggest that healthy Japanese may have more genu
      varus alignment compared to the corresponding Australian population. Age-related
      ethnic and gender differences in femoral and tibiofibular torsion are worthy of
      further study.

PMID- 16283647
TI  - The extensor indicis et medii communis.
AB  - The aim of this study was to examine the existence of the extensor indicis et
      medii communis in detail. Thirty-one randomly selected adult cadavers (62 upper
      extremities) were examined for this project (22 males and 9 females between the
      ages 38 and 87). The muscle was observed in 3 of 62 hands, an incidence of 4.8%.
      One was in the right and the other two were in the left hands. Mean length and
      width of the muscle belly were 4.5 +/- 0.8 and 0.8 +/- 0.3 mm, respectively.
      Although the muscle did not have a junctura tendinum attachment between its two
      tendons, in one hand, the tendon to the index finger gave a thin slip to the
      tendon of the extensor digitorum communis for the same finger. Knowledge of
      variant muscle may be important when one is assessing the traumatized or diseased
      hand.

PMID- 16283646
TI  - Rare additional renal artery in live-related transplantation.

PMID- 16283648
TI  - A cadaveric investigation into the links between macroscopic and microscopic
      osteoarthritic changes at the hip.
AB  - Our objective was to investigate the frequency and distribution of osteoarthritic
      changes at the hip, including the relationship between osteoarthritic lesions on
      the femoral head surface and histological changes in articular cartilage, in 12
      cadavers. Twelve embalmed cadavers (five males and seven females) were dissected,
      and the femoral head was removed from both sides (24 femoral heads). Any gross
      osteoarthritic changes were noted and graded (on a scale of 1-3). A circular disc
      was then removed from the equator of the femoral head and divided into nine
      regions. Out of 192 segments, 54 underwent sectioning and staining with
      haematoxylin and eosin to assess histological changes in cartilage.
      Osteoarthritis of the hip was present in all cadavers, with all males having
      bilateral OA and 50% having grade 2 or higher lesions (50% were grade 1), and
      four of the seven female specimens having bilateral OA and only 7% with grade 2
      lesions (with 71% grade 1 and 21% normal). Chondrocyte clustering was most
      commonly observed in the deep layer of cartilage followed by the intermediate and
      superficial layers respectively, as the grade of the macroscopic lesion
      increased. Cartilage injury at the histological level precedes any visible
      denudation of the femoral head articular cartilage. This study supports the
      hypothesis that early osteoarthritic changes occur in the deep layer of cartilage
      near the tide mark and progress superficially concomitant with an overall
      increase in the osteoarthritic lesion size on the femoral head surface.

PMID- 16283649
TI  - The posterior longitudinal ligament and peridural (epidural) membrane.
AB  - The posterior longitudinal ligament (PLL) is described as having deep and
      superficial layers, though recent studies have suggested that there may be three
      layers. Additional membranous structures have been reported, although there is no
      consensus as to their presence or morphology. The vertebral canal and dural sac
      were opened and the spinal nerve roots and spinal cord removed. The anterior
      dural ligaments were sectioned at their attachment to the PLL and the dura mater
      freed from the posterior surface of the vertebral bodies. The borders of the PLL
      were identified and the superficial and deep layers separated. The PLL is a wide
      band in the cervical region becoming more denticulate inferiorly, the widest
      parts being attached to the intervertebral discs (IVD) and adjacent vertebral
      body where the superficial and deep layers could not be separated. A continuous
      well developed peridural membrane attaching to the pedicles was present anterior
      to the deep PLL as well as a separate, thin, incomplete layer in 6 of 18
      cadavers, covering the posterior surface of the superficial PLL.

PMID- 16283650
TI  - Effects of static magnetic fields on growth of Paramecium caudatum.
AB  - Little is known about the influence of magnetic fields on growth of primitive
      eukaryotes such as the ciliate Paramecium. The latter are known to exhibit
      interesting characteristics such as electrotaxis, gravitaxis, and membrane
      excitability not commonly encountered in higher organisms. This preliminary study
      reports the effects of static magnetic fields on growth of Paramecium caudatum.
      The microorganisms were either permanently or 24 h on-and-off exposed to North
      and South polarity magnetic fields of average field gradient 4.3 T/m, for a
      period of 96 h. The growth rate and lag phase of all exposed populations were not
      significantly different from control ones exposed to normal geomagnetic field (P
      > .05). However, a significant negative shift in t(max) (time taken for maximum
      growth) of 10.5%-12.2% and a significant decrease (P < .05) in population size of
      10.2%-15.1% during the 96 h of experimental conditions were recorded for exposed
      populations compared to control. Our results suggest that magnetic fields,
      irrespective of polarity and exposure period reduce Paramecium growth by
      triggering early senescence of the population. The mechanisms underlying the
      small changes in population growth are unknown at this level, but various
      hypotheses have been suggested, including disorganization of swimming patterns
      resulting from (i) changes in cell membrane electric potential due to high speed
      movement through a gradient magnetic field and (ii) thermodynamic effect of
      anisotropic magnetic energies on cell membrane components affecting functioning
      of calcium channels. Altered swimming movements could in turn affect highly
      orchestrated processes such as conjugation, essential for survival of the
      organisms during development of adverse environmental conditions as thought to
      occur in the closed culture system used in this study.

PMID- 16283651
TI  - Influence of strong static magnetic fields on primary cortical neurons.
AB  - Intense uniform magnetic fields, such as those used in magnetic resonance imaging
      (MRI), are thought to exert little influence at the cellular level. Here we
      report modifications of the signaling cascades in rat cortical neurons cultured
      for 1 h in magnetic fields of up to 5 Tesla. The activation of c-Jun N-terminal
      kinase (JNK) increases monotonically with field strength, with a maximal
      activation of approximately 10% at 5 T, whereas the activation of extra cellular
      regulated kinase (ERK) shows a maximum at 0.75 T ( approximately 10%). Since ERK
      is involved in cellular differentiation, these results indicate a magnetic
      induction of the signaling events associated with differentiation. However, the
      cells respond to further increases in field strength by evoking a stress
      response, since JNK is a stress-activated protein kinase. Three possible
      mechanisms are discussed and of these, the most plausible is magnetic field
      induced change in the membrane rest potential, a microscale magnetohydrodynamic
      effect. This mechanism most likely involves the activation of voltage dependent
      Ca(2+) channel opening; since intracellular Ca(2+) concentration was also found
      to be modified by the static magnetic field.

PMID- 16283652
TI  - Survey of RF exposure levels from mobile telephone base stations in Australia.
AB  - This paper reports the results of an exposure level survey of radiofrequency
      electromagnetic energy originating from mobile telephone base station antennas.
      Measurements of CDMA800, GSM900, GSM1800, and 3G(UMTS) signals were performed at
      distances ranging over 50 to 500 m from 60 base stations in five Australian
      cities. The exposure levels from these mobile telecommunications base stations
      were found to be well below the general public exposure limits of the ICNIRP
      guidelines and the Australian radiofrequency standard (ARPANSA RPS3). The highest
      recorded level from a single base station was 7.8 x 10(-3) W/m(2), which
      translates to 0.2% of the general public exposure limit.

PMID- 16283653
TI  - Effect of extremely low frequency magnetic fields on calpain activation.
AB  - The effects of low intensity, low frequency magnetic fields (MFs) on catalytic
      activity of the calcium dependent protease calpain was determined following the
      enzyme activation both in "in vitro" and "in vivo" conditions. We have observed
      that a 0.3 mT MF induces a significant increase in the requirement of the
      protease for this metal ion. This change is detectable at low [Ca(2+)] and
      disappears when the level of Ca(2+) is raised to saturating amounts. The observed
      effects are not due to transient MF(-) induced conformational changes occurring
      in calpain, but to direct effects of the MF on Ca(2+) ions, which become less
      available for the binding sites present in calpain. Altogether, these results
      indicate that exposure to low intensity, low frequency MFs alters the
      intracellular Ca(2+) "availability," thereby modifying the related cell response.

PMID- 16283654
TI  - Divalent ion-binding properties of the two avian beta-parvalbumins.
AB  - Birds express three parvalbumins, one alpha isoform and two beta isoforms. The
      latter are known as avian thymic hormone (ATH) and avian parvalbumin 3. Although
      both were discovered in thymus tissue, and presumably function in T-cell
      maturation, they have been detected in other tissue settings. We have conducted
      detailed Ca2+- and Mg2+-binding studies on recombinant ATH and the C72S variant
      of CPV3, employing global analysis of isothermal titration calorimetry data. In
      Hepes-buffered saline, ATH binds Ca2+ with apparent microscopic binding constants
      of 2.4 +/- 0.2 x 10(8) and 1.0 +/- 0.1 x 10(8) M(-1). The corresponding values
      for CPV3-C72S are substantially lower, 4.5 +/- 0.5 x 10(7) and 2.4 +/- 0.2 x
      10(7) M(-1), a 1.9-kcal/mol difference in binding free energy. Thus, the beta
      parvalbumin lineage displays a spectrum of Ca2+-binding affinity, with ATH and
      the mammalian beta isoform at the high- and low-affinity extremes and CPV3 in the
      middle. Interestingly, despite its decreased Ca2+ affinity, CPV3-C72S exhibits
      increased affinity for Mg2+, relative to ATH. Whereas the latter displays Mg2+
      binding constants of 2.2 +/- 0.2 x 10(4) and 1.2 +/- 0.1 x 10(4) M(-1), CPV3-C72S
      yields values of 5.0 +/- 0.8 x 10(4) and 2.1 +/- 0.3 x 10(4) M(-1).

PMID- 16283655
TI  - Fast and versatile microwave-assisted intramolecular Heck reaction in peptide
      macrocyclization using microwave energy.
AB  - We have revisited the intramolecular Heck reaction and investigated the microwave
      assisted macrocyclization on preformed peptides using a model series of ring
      varying peptides acryloyl-Gly-[Gly](n)-Phe(4-I)NHR; n = 0-4. The method was
      applied to both solution and solid supported cyclizations. We demonstrate that
      the intramolecular Heck reaction can be performed in peptides both in solution
      and solid support using a modified domestic microwave within 1 to 30 minutes in
      DMF under reflux with moderate yields ranging from 15 to 25% for a scale between
      2-45 mg of linear precursors. The approach was applied to the synthesis of a
      constrained biologically relevant peptidomimetic bearing an Arg-Gly-Asp (RGD)
      sequence. These results make the microwave-assisted Heck reaction an attractive
      renovated approach for peptidomimetics.

PMID- 16283656
TI  - Asymmetric enone epoxidation by short solid-phase bound peptides: further
      evidence for catalyst helicity and catalytic activity of individual peptide
      strands.
AB  - In the presence of short solid-phase bound peptide catalysts, the Julia-Colonna
      epoxidation of enones (such as chalcone) with hydrogen peroxide can be performed
      with high enantiomeric excess (> or = 95% ee). It was proposed earlier (A.
      Berkessel, N. Gasch, K. Glaubitz, C. Koch, Organic Letters, 2001, Vol. 3, pp.
      3839-3842) that this remarkable catalysis is governed by the N-terminus of
      individual and helical peptide strands. This mechanistic proposal was scrutinized
      further. (i) Nonaggregation of the peptide catalysts: five solid-phase bound
      statistic mixtures (0/100; 30/70; 50/50; 70/30; 100/0) of D-Leu and L-Leu
      heptamers were generated and assayed as catalysts. A linear dependence of the
      epoxide ee on the enantiomeric composition of the catalysts resulted. (ii)
      Catalyst helicity [introduction of the helix-stabilizing C(alpha)-methyl-L
      leucine, L-(alphaMe)Leu]: solid-phase bound Leu/(alphaMe)Leu-pentamers of
      composition TentaGel-NH-[(alphaMe)-L-Leu]n-(L-Leu)m-H (n = 0-4; m = 5-n) were
      prepared and assayed as catalysts. The introduction of up to two (alphaMe)-L-Leu
      residues (n = 1, 2) significantly enhanced the catalyst activity relative to the
      L-Leu homopentamer (n = 0). Higher (alphaMe)-L-Leu contents (n = 3, 4) led to a
      decrease in both catalyst activity and enantiopurity of the product epoxide. In
      summary, both the individual catalytic action of the peptide strands and the
      helical conformation as the catalytically competent state of the peptide
      catalysts were further supported.

PMID- 16283657
TI  - Multiple variations in the paired arteries of the abdominal aorta.
AB  - Variations in the origin of arteries in the abdomen are very common. The arteries
      that show frequent variations include the celiac trunk, renal arteries, and
      gonadal arteries. We observed multiple variations in a 45-year-old male cadaver.
      The variations found on the left side were: one accessory renal artery, two
      testicular arteries, and middle suprarenal and inferior phrenic arteries that
      branched from the celiac trunk. On the right side, the inferior phrenic and
      middle suprarenal arteries arose from the right renal artery.

PMID- 16283658
TI  - Lap-belt injury with complete avulsion of the spinal cord and cauda equina.
AB  - The authors report a child who was involved in an automobile accident. The
      patient was restrained by a rear seat lap belt. Radiological examination revealed
      an L4 Chance-type fracture and ligamentous disruption at the L4-L5 interval.
      During superficial dissection of the paraspinal muscles for a spinal fusion
      procedure, the cauda equina and the lower spinal cord (several centimeters) were
      visible, completely transected and herniated into the extraspinal space through a
      disrupted thoracolumbar fascia. The clinician should be aware of the potentially
      devastating results following a lap-belt injury in which a Chance fracture is
      produced.

PMID- 16283659
TI  - Clinical histology.

PMID- 16283661
TI  - Abnormal branch of the testicular artery.
AB  - We present a case report of an abnormal course and branching of the right
      testicular artery, which was uncovered during routine dissection of the abdomen
      in our first year medical class. It arose from the anterior surface of the
      abdominal aorta and immediately divided into two branches; one branch coursed
      inferiorly behind the inferior vena cava as the testicular artery proper, while
      the other branch passed behind the inferior vena cava and emerged on the anterior
      surface of the right kidney. After crossing the anterior surface of the kidney,
      it bifurcated into an ascending branch that went to the right suprarenal gland
      and a descending branch that ended in the posterior abdominal wall. The left
      testicular artery was normal in its course and distribution. This is a very rare
      variation.

PMID- 16283660
TI  - Multidetector row CT demonstration of inner and middle ear structures.
AB  - The aim of this study is to evaluate the anatomical details of the inner ear and
      middle ear, using multidetector row CT. Temporal bone CT scans were obtained
      using 16-detector row CT scanner (Lightspeed 16, General Electric Medical
      Systems, Milwaukee, WI) in 30 patients with dizziness, vertigo, or hearing loss.
      The three-dimensional (3D) images were reconstructed with volume rendering
      techniques. The 3D images were reviewed by two radiologists and scored by using a
      three-point quality rating for qualitative assessment of the 23 representative
      structures of the middle and inner ear. The malleus, incus, and facial nerve
      canal were identified in all patients. The incudomalleolar joint appeared fused
      in all patients. The stapes were seen clearly in 27 (90%) of 30 patients except
      in three patients. Among the three remaining patients, there was one who had
      effusions in the middle ear cavity. Another patient had left cholesteatoma. The
      third patient had normal middle ear cavity. The cochlea and the three
      semicircular canals (anterior, posterior, and lateral) were well demonstrated in
      29 (97%) of 30 patients except for one old woman with osteoporosis. Sixteen
      detector row CT imaging of temporal bone with advanced 3D reformation yields
      state-of-the-art anatomical details of the temporal region useful to address
      anatomical localization issues and ease conceptual structural learning.

PMID- 16283662
TI  - Stochastic dynamics of magnetosomes and a mechanism of biological orientation in
      the geomagnetic field.
AB  - The rotations of nanoscopic magnetic particles, magnetosomes, embedded into the
      cytoskeleton are considered. Under the influence of thermal disturbances, a great
      number of magnetosomes are shown to move chaotically between two stable
      equilibrium positions, in which their magnetic moments are neither parallel nor
      antiparallel to the static Earth's magnetic field (MF). The random rotations
      attain the value of order of a radian. The rate of the transitions and the
      probability of magnetosomes to be in the different states depend on the MF
      direction with respect to an averaged magnetosome's orientation. This effect
      explains the ability of migratory animals to orient themselves faultlessly in
      long term passages in the absence of the direct visibility of optical reference
      points. The sensitivity to deviation from an "ideal" orientation is estimated to
      be 2-4 degrees. Possible involvement of the stochastic dynamics of magnetosomes
      in biological magnetic navigation is discussed.

PMID- 16283663
TI  - DNA strand breaks are not induced in human cells exposed to 2.1425 GHz band CW
      and W-CDMA modulated radiofrequency fields allocated to mobile radio base
      stations.
AB  - We conducted a large-scale in vitro study focused on the effects of low level
      radiofrequency (RF) fields from mobile radio base stations employing the
      International Mobile Telecommunication 2000 (IMT-2000) cellular system in order
      to test the hypothesis that modulated RF fields may act as a DNA damaging agent.
      First, we evaluated the responses of human cells to microwave exposure at a
      specific absorption rate (SAR) of 80 mW/kg, which corresponds to the limit of the
      average whole body SAR for general public exposure defined as a basic restriction
      in the International Commission on Non-Ionizing Radiation Protection (ICNIRP)
      guidelines. Second, we investigated whether continuous wave (CW) and Wideband
      Code Division Multiple Access (W-CDMA) modulated signal RF fields at 2.1425 GHz
      induced different levels of DNA damage. Human glioblastoma A172 cells and normal
      human IMR-90 fibroblasts from fetal lungs were exposed to mobile communication
      frequency radiation to investigate whether such exposure produced DNA strand
      breaks in cell culture. A172 cells were exposed to W-CDMA radiation at SARs of
      80, 250, and 800 mW/kg and CW radiation at 80 mW/kg for 2 and 24 h, while IMR-90
      cells were exposed to both W-CDMA and CW radiations at a SAR of 80 mW/kg for the
      same time periods. Under the same RF field exposure conditions, no significant
      differences in the DNA strand breaks were observed between the test groups
      exposed to W-CDMA or CW radiation and the sham exposed negative controls, as
      evaluated immediately after the exposure periods by alkaline comet assays. Our
      results confirm that low level exposures do not act as a genotoxicant up to a SAR
      of 800 mW/kg.

PMID- 16283664
TI  - Childhood leukemia and residential magnetic fields: are pooled analyses more
      valid than the original studies?
AB  - The association seen in epidemiological studies between childhood leukemia and
      magnetic field strength in the child's home has been very important in
      influencing reviews of international groups and standard setting organizations.
      This association is usually based on the results of two published pooled
      analyses, which use definitions of exposure that differ from those of some the
      original studies. However, the results and conclusions of the pooled analyses
      differ from those of the three largest recent studies, which have the most
      sophisticated methodology and together account for the majority of the exposed
      cases at high exposure levels in the pooled analyses. These recent studies, using
      the exposure methods and the cut-off levels set a priori, each concluded that
      there was little evidence of any association. The pooled analyses, using
      different exposure measures and different cut-offs, conclude that an association
      exists at high exposure levels. It is not clear if the results of the pooled
      analysis are more valid than those of the recent major studies, although this has
      been often assumed in influential reviews.

PMID- 16283665
TI  - Toxicity bioassay in Sprague-Dawley rats exposed to 20 kHz triangular magnetic
      field for 90 days.
AB  - Sprague-Dawley rats (10 each of male and female per group for sham and magnetic
      field exposed) were exposed in a carrousel irradiator to 20 kHz intermediate
      frequency (IF) magnetic field at 6.25 microT rms for 8 h/day, 5 days/week for 90
      days. Urine analysis (pH, serum glucose, protein, ketone bodies, RBC, WBC,
      bilirubin, urobilinogen, and specific gravity), blood analysis [WBC, RBC,
      hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular
      hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), thrombocyte
      count, and leucocyte count], blood biochemistry (total protein, blood urea
      nitrogen, creatinine, glucose, total bilirubin, total cholesterol, aspartate
      aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate
      dehydrogenase), and histopathological analysis for organs such as liver, kidney,
      testis, ovary, spleen, brain, heart, and lung were performed on day 90. Results
      showed no significant differences in the above analyses between IF magnetic field
      exposed and sham control rats. Therefore, we conclude that there were no
      significant toxicities in rats exposed to 20 kHz IF triangular magnetic field
      exposure for 90 days.

PMID- 16283666
TI  - Electrostatic calculations for assignment of infrared difference bands to
      carboxyl groups getting protonated during protein reactions.
AB  - Fourier transform infrared (FTIR) difference spectroscopy is predestined to
      monitor the protonation of carboxyl groups during protein reactions, making
      glutamic and aspartic amino acids unique to follow proton pathways. The
      absorption of the corresponding vibrations are clearly distinguishable from the
      absorption of other amino acids. However, the assignment to specific groups
      within the protein needs additional information, e.g., from induced spectral
      changes due to isotopic labeling or mutation. Here, the capability of
      electrostatic calculations to assign IR difference bands to specific carboxyl
      groups getting protonated is demonstrated by the ion pump mechanism of the
      sarcoplasmic reticulum Ca(2+)-ATPase. Active Ca(2+) transport is coupled to the
      hydrolysis of ATP. Two Ca(2+) ions are transported per ATP hydrolysed and two or
      three H(+) ions are countertransported. FTIR difference spectra show that during
      the Ca(2+) release step, carboxyl groups become protonated. Multiconformation
      continuum electrostatic calculations (MCCE) have been carried out to determine
      the equilibrium distribution of residue ionization and side chain conformation in
      dependence of pH. Available structural X-ray data from the calcium-bound and the
      calcium-free state allows us to simulate the transition between the two states
      monitored in the IR difference spectra. Exemplarily for Asp 800, ligand of both
      calcium ions, it is shown that MCCE calculations can identify this specific Asp
      to contribute to the IR bands and therefore to take part in the proton
      countertransport of the Ca(2+)-ATPase. In addition, an energy analysis can be
      performed to understand what interactions shift the pK(a).

PMID- 16283667
TI  - Interfacial behavior of cytoplasmic and mitochondrial creatine kinase oligomeric
      states.
AB  - Adsorption to the air/water interface of isoenzymes of creatine kinase was
      investigated using surface pressure-area isotherms and Brewster angle microscopy
      (BAM) observations. Octameric mitochondrial creatine kinase (mtCK) exhibits a
      significant affinity for the air/water interface. Whatever the mode of formation
      of the interfacial film, i.e., injection of the protein in the subphase or
      spreading onto the buffer surface, the final arrangement and conformation adopted
      by mtCK molecules lead to a similar result. In contrast, the dimeric isoenzymes
      mtCK and cytosolic MMCK do not induce any surface pressure variation. However,
      when the subphase contains 0.3M NaCl, both isoenzymes adsorb to the interface.
      When treated with 0.8 or 3M GdnHCl, muscle creatine kinase (MMCK) becomes surface
      active and occupies a greater surface than mtCK. This result contrasts with
      previous observations, often derived from monomeric proteins, that their surface
      activity is increased upon unfolding. It underlines the possible influence
      exerted by the protein oligomeric state on its interfacial activity. At a
      subphase pH of 8.8, which corresponds to the pI of octameric mtCK, the profiles
      of the isotherms obtained with dimeric and octameric states and the resistance to
      compression of the protein monolayers are significantly affected when compared to
      those recorded at pH 7.4. These data suggest that the octamer is more hydrophobic
      than the dimer and may contribute to explaining why octamers bind to the inner
      mitochondrial membrane while dimers do not.

PMID- 16283669
TI  - Submicroscopic deletions and duplications in individuals with intellectual
      disability detected by array-CGH.
AB  - Intellectual disability (ID) affects about 3% of the population (IQ < 70), and in
      about 40% of moderate (IQ 35-49) to severe ID (IQ < 34), and 70% of cases of mild
      ID (IQ 50-70), the etiology of the disease remains unknown. It has long been
      suspected that chromosomal gains and losses undetectable by routine cytogenetic
      analysis (i.e., less than 5-10 Mb in size) are implicated in ID of unknown
      etiology. Array CGH has recently been used to perform a genome-wide screen for
      submicroscopic gains and losses in individuals with a normal karyotype but with
      features suggestive of a chromosome abnormality. In two recent studies, the
      technique has demonstrated a approximately 15% detection rate for de novo copy
      number changes of individual clones or groups of clones. Here, we describe a
      study of 22 individuals with mild to moderate ID and nonsyndromic pattern of
      dysmorphic features suspicious of an underlying chromosome abnormality, using the
      3 Mb and 1 Mb commercial arrays (Spectral Genomics). Deletions and duplications
      of 16 clones, previously described to show copy number variability in normal
      individuals [Iafrate et al., 2004; Lapierre et al., 2004; Schoumans et al., 2004;
      Vermeesch et al., 2005] were seen in 21/22 subjects and were considered
      polymorphisms. In addition, three subjects showed submicroscopic deletions and
      duplications not previously reported as normal variants. Two of these
      submicroscopic changes were of de novo origin (microdeletions at 7q36.3 and a
      microduplication at 11q12.3-13.1) and one was of unknown origin as parental
      testing of origin could not be performed (microduplication of Xp22.3). The
      clinical description of the three subjects with submicroscopic chromosomal
      changes at 7q36.3, 11q12.3-13.1, Xp22.3 is provided.

PMID- 16283668
TI  - Promotor genotype of the platelet-derived growth factor receptor-alpha gene shows
      population stratification but not association with spina bifida meningomyelocele.
AB  - Neural tube defects (NTDs) constitute a major group of congenital malformations
      with an overall incidence of approximately 1-2 in 1,000 live births in the United
      States. Hispanic Americans have a 2.5 times higher risk than the Caucasian
      population. Spina bifida meningomyelocele (SBMM) is a major clinical presentation
      of NTDs resulting from lack of closure of the spinal cord caudal to the head. In
      a previous study of spina bifida (SB) patients of European Caucasian descent, it
      was suggested that specific haplotypes of the platelet-derived growth factor
      receptor-alpha (PDGFRA) gene P1 promoter strongly affected the rate of NTD
      genesis. In our study, we evaluated the association of PDGFRA P1 in a group of
      407 parent-child triads (167 Caucasian, 240 Hispanics) and 164 unrelated controls
      (89 Caucasian, 75 Hispanic). To fully evaluate the association of PDGFRA P1, we
      performed both transmission-disequilibrium test (TDT) and association analyses to
      test the hypotheses that PDGFRA P1 was (1) transmitted preferentially in SBMM
      affected children and (2) associated with the condition of SBMM comparing
      affected children to unaffected controls. We did find that there was a different
      allelic and genotypic distribution of PDGFRA P1 when comparing Hispanics and
      Caucasians. However, neither ethnic group showed strong association between SBMM
      and the PDGFRA P1 region. These findings suggest that PDGFRA P1 does not have a
      major role in the development of SBMM.

PMID- 16283670
TI  - Systemic lupus erythematosus and other autoimmune disorders in children with
      Noonan syndrome.

PMID- 16283671
TI  - Changes in hair morphology of mucopolysaccharidosis I patients treated with
      recombinant human alpha-L-iduronidase (laronidase, Aldurazyme).
AB  - Mucopolysaccharidoses (MPS) are heritable, metabolic diseases caused by
      accumulation of mucopolysaccharides (glycosaminoglycans, GAGs) in lysosomes. This
      accumulation is due to a deficiency in one of several specific enzymes involved
      in the degradation of GAGs. MPS type I (MPS I) is caused by low or undetectable
      activity of alpha-L-iduronidase, an enzyme involved in removing the terminal
      iduronic acid residues from heparan and dermatan sulfate. Recently, an enzyme
      replacement therapy (ERT) for MPS I, based on administration of recombinant human
      alpha-L-iduronidase (laronidase, Aldurazyme), became available. The assessment of
      efficacy of ERT is especially important because MPS I is a highly variable and
      very rare disease, and the clinical trials involved relatively low number of
      patients. Among various significant clinical improvements during ERT, remarkable
      changes in hair morphology were noted. Detailed studies of hair samples from one
      patient, who did not have a hair cut from the beginning of ERT to the end of this
      study, and supported by results obtained for two other patients, revealed hair
      shaft structural abnormalities in MPS I hair. These hair abnormalities
      disappeared upon treatment with Aldurazyme. Although hair morphology is of
      limited clinical importance, the data suggest that changes in this parameter
      could be a useful, additional tool for a rapid, non-invasive, preliminary
      assessment of ERT efficacy.

PMID- 16283672
TI  - Sequence variations in AGTR2 are unlikely to be associated with X-linked mental
      retardation.

PMID- 16283673
TI  - Cardiovascular malformations in Fryns syndrome: is there a pathogenic role for
      neural crest cells?
AB  - We performed a comprehensive literature and case report review to characterize
      the cardiovascular malformations (CVMs) associated with Fryns syndrome (OMIM
      #229850), a multiple congenital anomaly/mental retardation syndrome consisting of
      diaphragmatic defects, significant pulmonary hypoplasia, distinctive facial
      appearance, distal digital hypoplasia, and numerous other external and internal
      anomalies. A total of 112 patients meeting diagnostic guidelines for Fryns
      syndrome were identified, of whom 82 met narrowly defined criteria (Group I) and
      30 met broader diagnostic criteria (Group II). Twelve patients reported as having
      Fryns syndrome with atypical features (Group III) were also analyzed. A CVM was
      reported in 51% (42 of 82) of Group I patients, most commonly an atrial or
      ventricular septal defect (VSD) (23 of 42, 55%). Conotruncal and aortic arch CVMs
      were common (11 of 42, 26%), but not significantly so compared to the general
      population of infants to age 1 year [Ferencz et al., 1997]. Recognizing that
      minor septal defects associated with congenital diaphragmatic hernia (CDH) may
      occur in response to altered hemodynamics (instead of being a bonafide CVM), we
      excluded four patients reported as having hemodynamically insignificant VSDs.
      Following these exclusions, conotruncal CVMs were found more commonly than in the
      general population (11 of 38, 29%, P < or = 0.025). In Group II, 9 of 30 (30%)
      had a CVM with no predominant type among the small number of cases reviewed.
      Among the atypical Fryns syndrome patients in Group III, half (6 of 12, 50%) had
      a CVM; most (4 of 6, 67%) were conotruncal, in particular, type B interrupted
      aortic arch (3 of 4). Patients with Fryns syndrome have a high rate of CVMs,
      warranting thorough cardiac evaluation including echocardiogram (fetal and/or
      postnatal) in all patients, similar to the evaluation for other patients with
      diaphragmatic hernia. The possible association between conotruncal CVMs and Fryns
      syndrome may provide additional support for an etiologic role of genes related to
      neural crest cell development in the pathogenesis of Fryns syndrome and hence,
      congenital diaphragmatic hernia.

PMID- 16283674
TI  - Epidemiology of hemimegalencephaly: a case series and review.
AB  - Hemimegalencephaly (HME) is a congenital brain malformation characterized by
      unilateral enlargement of the cerebral hemisphere. Clinically, HME is typically
      associated with hemiparesis, psychomotor retardation, and intractable seizures
      usually apparent soon after birth. HME is often an isolated finding, but it has
      been described as an occasional feature of a large number of syndromes, many of
      which may not be readily identified at birth. There are a multitude of case
      series and reports of HME in the English literature; however, there is no
      comprehensive, unbiased, detailed survey characterizing the proportion of cases
      of HME that are associated with a syndrome. We performed a retrospective study of
      all cases of HME seen at our institution from 1990 to 2003. Of the 15 cases of
      HME identified, 53% (8/15) were non-syndromic and 47% (7/15) of the cases were
      associated with a known or suspected genetic syndrome. In patients with syndromic
      HME, many of the syndromic features were not readily discernible at birth or in
      early infancy. It is, therefore, imperative to continually evaluate any infant
      with HME for signs and symptoms of these and other syndromes. Knowing the
      relative differential diagnosis will lead to a more comprehensive evaluation,
      improvement in expectant management, and appropriate counseling of families
      before considering radical surgical options such as hemispherectomy.

PMID- 16283676
TI  - Rheumatoid arthritis, a complex multifactorial disease: on the way toward
      individualized medicine.
AB  - With the availability of the human genome sequence and those of related species
      like chimpanzee, mouse, and rat, data driven research for tackling the molecular
      grounds of rheumatoid arthritis (RA), a multifactorial polygenic disease, can be
      considered a realistic challenge to the scientific community. A comprehensive
      research strategy is presented enabling the integration of multiple research
      efforts on studying autoimmunity by so called systems biology approaches. An
      integrative scientific concept is discussed of how to unravel molecular
      mechanisms of complex diseases by making use of state-of-the-art methodologies in
      functional and comparative genomics. A continuous interchange of data-driven and
      hypothesis-driven research is adjoined to determine the nature of rheumatic
      diseases with autoimmune background. Instead of studying single genes and
      proteins, RNA and protein microarray profiles are currently obtained in numerous
      research projects producing read-outs termed gene signatures rather than DNA
      and/or protein markers. A comprehensive study of the RNA, protein, and metabolite
      regimes is undertaken that eventually will lead to a "holistic" view of how all
      respective molecules, pathways and cells themselves interact with each other.
      Some of the above mentioned research aspects have already been studied by the
      authors, hopefully leading to new diagnostics and therapeutics in the future.

PMID- 16283677
TI  - Small molecular anti-cytokine agents.
AB  - The recent successful introduction of the anti-cytokine biologicals Etanercept,
      Infliximab, Adalimumab, and Anakinra has stimulated the search for anti-cytokine
      small-molecules. A number of molecular targets have been identified for the
      development of such small molecular anti-cytokine agents. The focus of this
      review will be on those inhibitors of cytokine production, which target either
      p38 mitogen activated protein (MAP) kinase, TNF-alpha converting enzyme (TACE),
      or IL-1beta converting enzyme (ICE). P38 MAP kinase occupies a central role in
      the signaling network responsible for the upregulation of proinflammatory
      cytokines like interleukin 1beta (IL-1beta) and TNF-alpha, and regulates their
      biosynthesis at both the transcriptional and translational level. TACE and ICE
      are two proteases required for the processing of proTNF-alpha and proIL-1beta,
      respectively into their mature, proinflammatory form. Since the mid-1990s, a
      plethora of inhibitors of p38 MAP kinase, TACE, and ICE has been characterized in
      vitro, and individual representatives from all three inhibitor classes have in
      the meantime been advanced into clinical trials. This review will highlight the
      correlation between effective inhibition at the molecular target and cellular
      activity in functional assays of cytokine, particularly TNF-alpha and IL-1beta,
      production. Structure-activity relationships (SAR) will be discussed regarding
      activity at the respective enzyme target, but also with regard to properties
      required for efficient in vitro and in vivo cellular activity (e.g., oral
      availability, solubility, cell penetration, etc.).

PMID- 16283678
TI  - Neurofibromatosis von Recklinghausen type I phenotype and early onset of cancers
      in siblings compound heterozygous for mutations in MSH6.
AB  - We report on a nonconsanguineous family in which two siblings with cutaneous
      manifestations leading to a diagnosis of neurofibromatosis type 1 (NF1) developed
      CNS tumors at an early age. In addition, one of them developed a T-cell lymphoma.
      Neither parent had NF1. The mother was known to be heterozygous for a MSH6
      mutation, and the father was found to be heterozygous for a different MSH6
      mutation. Screening of MSH2, MLH1, MSH6, PMS1, PMS2, and MLH3 in the affected
      children disclosed that they both were compound heterozygote for the MSH6
      mutations of their parents. Most recently, about a dozen other cases of inherited
      bi-allelic deficiency of mismatch repair (MMR) genes associated with early onset
      CNS tumors, hematologic malignancy, gastrointestinal neoplasia, cafe-au-lait
      spots, and other NF1 features have been reported. In the present study, we
      summarize the clinical findings of 27 individuals homozygous or compound
      heterozygous for an MMR gene mutation reported in the medical literature. We
      suggest that biparentally inherited mutations of one of the MMR genes should be
      considered in children with multiple cafe-au-lait spots who have early-onset CNS
      tumors, hematologic malignancies, or early onset gastrointestinal neoplasia.

PMID- 16283679
TI  - An Xq22.3 duplication detected by comparative genomic hybridization microarray
      (Array-CGH) defines a new locus (FGS5) for FG syndrome.
AB  - FG syndrome is an X-linked multiple congenital anomalies (MCA) syndrome. It has
      been mapped to four distinct loci FGS1-4, through linkage analysis (Xq13, Xp22.3,
      and Xp11.4-p11.3) and based on the breakpoints of an X chromosome inversion
      (Xq11:Xq28), but so far no gene has been identified. We describe a boy with FG
      syndrome who has an inherited duplication at band Xq22.3 detected by comparative
      genomic hybridization microarray (Array-CGH). These duplication maps outside all
      four loci described so far for FG syndrome, representing therefore a new locus,
      which we propose to be called FGS5. MID2, a gene closely related to MID1, which
      is known to be mutated in Opitz G/BBB syndrome, maps within the duplicated
      segment of our patient. Since FG and Opitz G/BBB syndromes share many
      manifestations we considered MID2 a candidate gene for FG syndrome. We also
      discuss the involvement of other potential genes within the duplicated segment
      and its relationship with clinical symptoms of our patient, as well as the
      laboratory abnormalities found in his mother, a carrier of the duplication.

PMID- 16283681
TI  - Mycophenolic acid-eluting stent and the ABC's of stent-based immunosuppressive
      therapies for the prevention of restenosis.

PMID- 16283680
TI  - IMPACT Trial: angiographic and intravascular ultrasound observations of the first
      human experience with mycophenolic acid-eluting polymer stent system.
AB  - The purpose of the study was to examine the safety and efficacy of two different
      formulations of mycophenolic acid (MPA)-eluting Duraflex stents on coronary de
      novo lesions. Recent data indicate that local delivery of MPA in the porcine
      overstretch coronary model significantly reduces neointimal hyperplasia (NIH).
      Patients were divided into three consecutive groups. The first (n=50) and second
      (n=55) groups received moderate- and slow-release MPA-eluting Duraflex stent,
      respectively. The last group (n=50) received the bare metal Duraflex stent.
      Clinical, angiographic, and intravascular ultrasound analysis were performed at 6
      month follow-up. All stents were successfully deployed and patients were
      discharged home without clinical events. Compared to controls, 6-month in-lesion
      and in-stent minimum luminal diameter as well as late lumen loss were not
      significantly different in the moderate- and slow-release treatment groups. At
      follow-up, percentage obstruction and NIH volume were also similar between the
      three groups. At 30 days and 6 and 12 months, there were no differences noted
      between the three groups with respect to major adverse cardiac events as well as
      the individual rates of mortality, myocardial infarction, or repeat
      revascularization. There were no cases of subacute or late thrombosis. In this
      feasibility trial, the MPA-eluting Duraflex stents in either slow- or moderate
      release formulations were well tolerated, but showed no benefit for treatment of
      coronary lesions when compared to controls. Further testing with different drug
      dosing or delivery rate might improve these results.

PMID- 16283682
TI  - Pilot study with an intensified oral sirolimus regimen for the prevention of in
      stent restenosis in de novo lesions: a serial intravascular ultrasound study.
AB  - This pilot study evaluated the safety and efficacy of an intensified oral
      sirolimus regimen (15-mg loading dose 24 hr before PCI, followed by a daily dose
      of 5 mg for 4 weeks) in 15 patients subjected to elective bare metal coronary
      stent implantation for de novo lesions. Mean patient age was 59+/-9; 73% were
      male, and 13% were diabetic patients. The reference diameter was 3.04+/-0.38 mm,
      and the lesion length was 14+/-2 mm. Angiographic and volumetric intravascular
      ultrasound (IVUS) analyses were performed in all patients at 6.0+/-0.2 months.
      Two patients (13%) met the definition of in-segment binary restenosis; in-stent
      and in-segment angiographic late loss was 0.61+/-0.31 mm and 0.67+/-0.45 mm,
      respectively, and the percent neointimal volume was 28.5+/-15.8%. At adjacent
      reference segments, there was neither significant plaque increase nor
      constrictive vascular remodeling. At 24-month follow-up no deaths, myocardial
      infarctions, or target lesion revascularizations were detected. Mean sirolimus
      blood level was 13+/-7 ng/ml. No correlations were found between drug levels and
      late loss (r=0.15, P=0.59) or IVUS percent neointimal volume (r=0.23, P=0.47).
      Side effects were frequent (80%), leading to dose reductions in four and drug
      discontinuation in one patient. The results of this pilot study suggest that an
      intensified 5-mg oral sirolimus regimen resulted in no relevant improvements in
      the angiographic and IVUS parameters of restenosis after stent implantation in de
      novo lesions when compared with historic controls. Considering the
      efficacy/safety balance, our results do not encourage further trials evaluating
      the current protocol for the prevention of in-stent restenosis.

PMID- 16283683
TI  - Total synthesis of (-)-samaderine Y from (S)-(+)-carvone.

PMID- 16283684
TI  - Soft nanotechnology with soft nanoparticles.
AB  - The last decade of research in the physical sciences has seen a dramatic increase
      in the study of nanoscale materials. Today, "nanoscience" has emerged as a
      multidisciplinary effort, wherein obtaining a fundamental understanding of the
      optical, electrical, magnetic, and mechanical properties of nanostructures
      promises to deliver the next generation of functional materials for a wide range
      of applications. While this range of efforts is extremely broad, much of the work
      has focused on "hard" materials, such as Buckyballs, carbon nanotubes, metals,
      semiconductors, and organic or inorganic dielectrics. Meanwhile, the soft
      materials of current interest typically include conducting or emissive polymers
      for "plastic electronics" applications. Despite the continued interest in these
      established areas of nanoscience, new classes of soft nanomaterials are being
      developed from more traditional polymeric constructs. Specifically,
      nanostructured hydrogels are emerging as a promising group of materials for
      multiple biotechnology applications as the need for advanced materials in the
      post-genomic era grows. This review will present some of the recent advances in
      the marriage between water-swellable networks and nanoscience.

PMID- 16283685
TI  - Synthetic substrates for an endoplasmic reticulum protein-folding sensor, UDP
      glucose: glycoprotein glucosyltransferase.

PMID- 16283686
TI  - Design and synthesis of oligosaccharides that interfere with glycoprotein quality
      control systems.
AB  - Calnexin (CNX) and its soluble homologue calreticulin (CRT) are lectin-like
      molecular chaperones that help newly synthesized glycoproteins to fold correctly
      in the rough endoplasmic reticulum (ER). To investigate the mechanism of
      glycoprotein-quality control, we have synthesized structurally defined high
      mannose-type oligosaccharides related to this system. This paper describes the
      synthesis of the non-natural undecasaccharide 2 and heptasaccharide 16, designed
      as potential inhibitors of the ER quality-control system. Each possesses the key
      tetrasaccharide element (Glc1Man3) critical for the CNX/CRT binding, while
      lacking the pentamannosyl branch required for glucosidase II recognition. These
      oligosaccharides were evaluated for their ability to bind CRT by isothermal
      titration calorimetry (ITC). As expected, each of them had a significant affinity
      towards CRT. In addition, these compounds were shown to be resistant to
      glucosidase II digestion. Their activities in blocking the chaperone function of
      CRT were next measured by using malate dehydrogenase (MDH) as a substrate. Their
      inhibitory effects were shown to correlate well with their CRT-binding
      affinities, both being critically dependent upon the presence of the terminal
      glucose (Glc) residue.

PMID- 16283687
TI  - Discovery of complex mixtures of novel long-chain quorum sensing signals in free
      living and host-associated marine alphaproteobacteria.
AB  - More than 100 bacterial isolates from various marine habitats were screened for
      AHL production by using gfp reporter constructs based on the lasR system of
      Pseudomonas aeruginosa and the luxR system of Vibrio fischeri. Of the 67
      Alphaproteobacteria tested, most of which belonged into the so-called Roseobacter
      clade, 39 induced fluorescence in either one or both sensor strains up to 103
      fold compared to controls. Acylated homoserine lactones were identified by GC-MS
      analysis and shown to have chain lengths of C8, C10, C13-C16, and C18. One or two
      double bonds were often present, while a keto or hydroxyl group occurred only
      rarely in the side chain. Most strains produced several different AHLs. C18-en
      HSL and C18-dien-HSL were produced by Dinoroseobacter shibae, an aerobic
      anoxygenic phototrophic bacterium isolated from dinoflagellates, and are among
      the longest AHLs found to date. Z7-C14-en-HSL, which has previously been detected
      in Rhodobacter sphaeroides, was produced by Roseovarius tolerans and Jannaschia
      helgolandensis. This signal molecule was synthesised and shown to induce a
      similar response to the culture supernatant in the respective sensor strain. The
      widespread occurrence of quorum-sensing compounds in marine Alphaproteobacteria,
      both free-living strains and those associated to eukaryotic algae, points to a
      great importance of this signalling mechanism for the adaptation of the organisms
      to their widely different ecological niches.

PMID- 16283688
TI  - LanV, a bifunctional enzyme: aromatase and ketoreductase during landomycin A
      biosynthesis.
AB  - LanV is involved in the biosynthesis of landomycin A. The exact function of this
      enzyme was elucidated with combinatorial biosynthesis by using Streptomyces
      fradiae mutants that produce urdamycin A. After expression of lanV in S. fradiae
      DeltaurdM, which is a mutant that accumulates rabelomycin, urdamycinon B and
      urdamycin B were found to be produced by the strain. This result indicates that
      LanV is involved in the 6-ketoreduction of the angucycline core, which preceeds a
      5,6-dehydration reaction. 9-C-D-Olivosyltetrangulol was also produced by this
      strain; this demonstrates that LanV catalyses the aromatization of ring A of the
      angucycline structure. Coexpression of lanV and lanGT2 in S. fradiae AO, a mutant
      that lacks all four urdamycin glycosyltransferases, resulted in the production of
      tetrangulol and the glycoside landomycin H, both of which have an aromatic ring
      A. As glycosylated angucyclines were not observed after expression of lanGT2 in
      the absence of lanV, we conclude that LanGT2 needs an aromatized ring A for
      substrate recognition.

PMID- 16283689
TI  - A designed well-folded monomeric four-helix bundle protein prepared by Fmoc solid
      phase peptide synthesis and native chemical ligation.
AB  - The design and total chemical synthesis of a monomeric native-like four-helix
      bundle protein is presented. The designed protein, GTD-Lig, consists of 90 amino
      acids and is based on the dimeric structure of the de novo designed helix-loop
      helix GTD-43. GTD-Lig was prepared by the native chemical ligation strategy and
      the fragments (45 residues long) were synthesized by applying standard
      fluorenylmethoxycarbonyl (Fmoc) chemistry. The required peptide-thioester
      fragment was prepared by anchoring the free gamma-carboxy group of Fmoc-Glu-allyl
      to the solid phase. After chain elongation the allyl moiety was orthogonally
      removed and the resulting carboxy group was functionalized with a glycine
      thioester followed by standard trifluoroacetic acid (TFA) cleavage to produce the
      unprotected peptide-thioester. The structure of the synthetic protein was
      examined by far- and near-UV circular dichroism (CD), sedimentation equilibrium
      ultracentrifugation, and NMR and fluorescence spectroscopy. The spectroscopic
      methods show a highly helical and native-like monomeric protein consistent with
      the design. Heat-induced unfolding was studied by tryptophan absorbance and far
      UV CD. The thermal unfolding of GTD-Lig occurs in two steps; a cooperative
      transition from the native state to an intermediate state and thereafter by
      noncooperative melting to the unfolded state. The intermediate exhibits the
      properties of a molten globule such as a retained native secondary structure and
      a compact hydrophobic core. The thermodynamics of GuHCl-induced unfolding were
      evaluated by far-UV CD monitoring and the unfolding exhibited a cooperative
      transition that is well-fitted by a two-state mechanism from the native to the
      unfolded state. GTD-Lig clearly shows the characteristics of a native protein
      with a well-defined structure and typical unfolding transitions. The design and
      synthesis presented herein is of general applicability for the construction of
      large monomeric proteins.

PMID- 16283690
TI  - Controlling stereochemical outcomes of asymmetric processes by catalyst remote
      molecular functionalizations: chiral diamino-oligothiophenes (DATs) as ligands in
      asymmetric catalysis.
AB  - The synthesis, characterization, and structure-guided application of a new class
      of highly versatile chiral C(2)-symmetric diamine-oligothiophene ligands in Pd
      catalyzed asymmetric transformations are presented. Experimental investigations
      of the intimate role of pendant pi-conjugate oligothiophenes in determining the
      catalytic activity of the corresponding chiral Pd complexes are described. Their
      unusual behavior opens up new routes toward the logical design of finely tuned
      organometallic catalysts by remote structural functionalizations.

PMID- 16283691
TI  - Fast and simultaneous detection of prominent natural antioxidants using
      analytical microsystems for capillary electrophoresis with a glassy carbon
      electrode: a new gateway to food environments.
AB  - This paper examines for the first time the analytical possibilities of fast and
      simultaneous detection of prominent natural antioxidants including examples of
      flavonoids and vitamins using a CE microchip with electrochemical detection (ED).
      Unpinched injection conditions, zone electrophoretic separation and amperometric
      detection were carefully assayed and optimised. Analysis involved the zone
      electrophoretic separation of arbutin, (+)-catechin and ascorbic acid in less
      than 4 min using a borate buffer (pH 9.0, 50 mM), employing 2 kV as the
      separation voltage and +1.0 V as the detection potential. In addition, the
      separation of different 'couples' of natural antioxidants of food significance
      including (+)-catechin and ascorbic acid, (+)-catechin and rutin, as well as
      arbutin and phlorizdin is proposed. To demonstrate the potential and future role
      of CE microsystems, analytical possibilities and a new route in the raw sample
      analysis are presented. The preliminary results obtained allow the proposal of CE
      ED microchips as a real gateway to microanalysis in foods.

PMID- 16283692
TI  - Detection of polymerase chain reaction fragments using a conducting polymer
      modified screen-printed electrode in a microfluidic device.
AB  - A simple and fast method for electrochemical detection of amplified fragments by
      PCR was successfully developed using CE in a microfluidic device with a modified
      screen-printed carbon electrode (SPCE). The surfaces of the SPCE were modified
      with poly-5,2'-5',2''-terthiophene-3'-carboxylic acid, which improves the
      analysis performance by lowering the detection potential, enhancing the S/N
      characteristics, and avoiding electrode poisoning. DNA fragments amplified by PCR
      were separated within 210 s in a 75.5 mm-long coated-separation channel at a
      separation field strength of -200 V/cm. To minimize the sample adsorption into
      the inner surface of the capillary wall, which disturbs the separation, a
      dynamically coated capillary with an acrylamide solution was used. Furthermore,
      the analysis procedure was simplified and rendered reproducible by using 0.50%
      w/v hydroxyethylcellulose as a separation matrix in a coated channel. The
      reproducibility of the analysis employing the coated channel yielded RSD of 4.3%
      for the peak areas and 1.4% for the migration times in eight repetitive
      measurements at a modified electrode, compared with 21.3 and 9.4% for a bare
      electrode. The sensitivity of the assay was 18.74 pAs/(pg/microL) with a
      detection limit of 584.31 +/- 1.3 fg/microL.

PMID- 16283693
TI  - Rapid on-chip postcolumn labeling and high-resolution separations of DNA.
AB  - When performing genetic analysis on microfluidic systems, labeling the sample DNA
      for detection is a critical preparation step. Labeling procedures often involve
      fluorescently tagged primers and PCRs, which lengthen experimental run times and
      introduce higher levels of complexity, increasing the overall cost per analysis.
      Alternatively, on-chip labeling techniques based on intercalating dyes permit
      rapid labeling of DNA fragments. However, as noted in the literature, the
      stochastic nature of dye-DNA complex formation hinders the native electrophoretic
      migration of DNA fragments, degrading the separation resolution. In this study,
      we present a novel method of controllably labeling DNA fragments at the end of
      the electrophoretic separation channel in a glass microfluidic chip. Permitting
      the DNA to separate and labeling just before detection, achieves the rapid
      labeling associated with intercalators while maintaining the high resolution of
      native DNA separations. Our analyses are completed in minutes, rather than the
      hours typical of sample prelabeling. We demonstrate an electrophoretic microchip
      based intercalator labeling technique that achieves higher resolution performance
      than reported in the literature to date.

PMID- 16283694
TI  - Fabrication of enclosed SU-8 tips for electrospray ionization-mass spectrometry.
AB  - We describe a novel electrospray tip design for MS which is fabricated completely
      out of SU-8 photoepoxy. A three-layer SU-8 fabrication process provides fully
      enclosed channels and tips. The tip shape and alignment of all SU-8 layers is
      done lithographically and is therefore very accurate. Fabrication process enables
      easy integration of additional fluidic functions on the same chip. Separation
      channels can be made with exactly the same process. Fluidic inlets are made in SU
      8 during the fabrication process and no drilling or other postprocessing is
      needed. Channels have been fabricated and tested in the size range of 10 microm x
      10 microm-50 microm x 200 microm. Mass spectrometric performance of the tips has
      been demonstrated with both pressure-driven flow and EOF. SU-8 microtips have
      been shown to produce stable electrospray with EOF in a timescale of tens of
      minutes. With pressure driven flow stable spray is maintained for hours. Taylor
      cone was shown to be small in volume and well defined even with the largest
      channel cross section. The spray was also shown to be well directed with our tip
      design.

PMID- 16283696
TI  - B vitamins and homocysteine.

PMID- 16283695
TI  - Gold nanoparticles for microfluidics-based biosensing of PCR products by
      hybridization-induced fluorescence quenching.
AB  - Colloidal gold nanoparticles were used to develop a simple microfluidics-based
      bioassay that is able to recognize and detect specific DNA sequences via
      conformational change-induced fluorescence quenching. In this method, a self
      assembled monolayer of gold nanoparticles was fabricated on the channel wall of a
      microfluidic chip, and DNA probes were bonded to the monolayer via thiol groups
      at one end and a fluorophore dye was attached to the other end of the probe. The
      created construct is spontaneously assembled into a constrained arch-like
      conformation on the particle surface and, under which, the fluorescence of
      fluorophores is quenched by gold nanoparticles. Hybridization of target DNAs
      results in a conformational change of the construct and then restores the
      fluorescence, which serves as a sensing method for the target genes. The
      nanocomposite constructed on the glass surface was characterized by UV absorbance
      measurement and the quenching efficiency for different fluorophores was evaluated
      by Stern-Volmer studies. The applicability of proposed assay was first
      demonstrated by the use of a pair of synthesized complementary and
      noncomplementary DNA sequences. The method was further applied for the detection
      of the PCR product of dengue virus with the use of enterovirus as the negative
      control, and results indicate that the assay is specific for the target gene.
      Moreover, using this approach, dehybridization, hybridization, and detection of
      the target genes can be performed in situ on the same microfluidic channel. Thus,
      this method could be regarded as one-pot reaction and it holds great promises for
      clinical diagnostics.

PMID- 16283697
TI  - Position on stem cell research.

PMID- 16283699
TI  - Internet dating slows HIV spread.

PMID- 16283698
TI  - Hopes dashed for formulation.

PMID- 16283700
TI  - Agreement advances microbicide research.

PMID- 16283701
TI  - The changing face of China.

PMID- 16283702
TI  - A defensive strategy.

PMID- 16283703
TI  - An easier route to employment.

PMID- 16283704
TI  - Biofabrication with chitosan.
AB  - The traditional motivation for integrating biological components into
      microfabricated devices has been to create biosensors that meld the molecular
      recognition capabilities of biology with the signal processing capabilities of
      electronic devices. However, a different motivation is emerging; biological
      components are being explored to radically change how fabrication is achieved at
      the micro- and nanoscales. Here we review biofabrication, the use of biological
      materials for fabrication, and focus on three specific biofabrication approaches:
      directed assembly, where localized external stimuli are employed to guide
      assembly; enzymatic assembly, where selective biocatalysts are enlisted to build
      macromolecular structure; and self-assembly, where information internal to the
      biological material guides its own assembly. Also reviewed are recent results
      with the aminopolysaccharide chitosan, a material that offers a combination of
      properties uniquely suited for biofabrication. In particular, chitosan can be
      directed to assemble in response to locally applied electrical signals, and the
      chitosan backbone provides sites that can be employed for the assembly of
      proteins, nucleic acids, and virus particles.

PMID- 16283705
TI  - Polypeptide multilayer films.
AB  - Research on polypeptide multilayer films, coatings, and microcapsules is located
      at the intersection of several disciplines: synthetic polymer chemistry and
      physics, biomaterials science, and nanoscale engineering. The past few years have
      witnessed considerable growth in each of these areas. Unexplored territory has
      been found at the borders, and new possibilities for technology development are
      taking form from technological advances in polypeptide production, sequencing of
      the human genome, and the nature of peptides themselves. Most envisioned
      applications of polypeptide multilayers have a biomedical bent. Prospects seem no
      less positive, however, in fields ranging from food technology to environmental
      science. This review of the present state of polypeptide multilayer film research
      covers key points of polypeptides as materials, means of polymer production and
      film preparation, film characterization methods, focal points of current research
      in basic science, and the outlook for a few specific applications. In addition,
      it discusses how the study of polypeptide multilayer films could help to clarify
      the physical basis of assembly and stability of polyelectrolyte multilayers, and
      mention is made of similarities to protein folding studies.

PMID- 16283706
TI  - Molecularly engineered nanocomposites: layer-by-layer assembly of cellulose
      nanocrystals.
AB  - Cellulose nanocrystals are promising as a new class of reinforcing material for
      the preparation of nanostructured composites. We report here the preparation of
      cellulose nanocrystal multilayer composites with poly(diallyldimethylammonium
      chloride) using layer-by-layer assembly (LBL) technique. The LBL assembly was
      characterized with UV-Vis spectroscopy and ellipsometry. The average thickness of
      a single bilayer was found to be 11 nm. AFM and SEM characterization revealed
      uniform coverage and densely packed cellulose crystal surface.

PMID- 16283707
TI  - Supramolecular conjugates of carbon nanotubes and DNA by a solid-state reaction.
AB  - DNA-wrapped nanotubes of both multiwalled and single-walled carbon nanotubes were
      obtained by a solid-state mechanochemical reaction. Scanning electron microscopic
      images show that the nanotubes were cut into shorter lengths and were fully
      covered with DNA, which was further confirmed by fluorescence microscopy. This
      resulted in a high aqueous solubility of the products with a stability of >6
      months. The results show that nanotubes were cut also with uniform distribution
      where >90% of the multiwalled products were 500 nm to 3 microm and 80% of the
      single-walled products were 250 nm to 1 microm in length, respectively. UV-vis
      spectra and gel electrophorosis show that the DNA in the product is intact. This
      facile technique for obtaining supramolecularly masked, water-soluble carbon
      nanotubes by a solid-state reaction has a great potential for both biological and
      nonbiological applications of nanotubes.

PMID- 16283708
TI  - Biomimetic gel exhibiting self-beating motion in ATP solution.
AB  - Biomimetic material systems using stimuli-responsive polymers and gels have been
      widely studied for applications to artificial muscles, drug delivery systems,
      biosensors, etc. In almost all cases, however, the action is driven by on-off
      switching of external signals. In contrast, here we show a novel biomimetic gel
      to exhibit autonomous self-beating motion in ATP solution under constant
      condition, similar to heart muscle. An anionic polymer gel with phosphoric
      groups, in which creatine kinase was immobilized, was prepared. When the gel was
      immersed in the ATP solution, the enzymatic reaction occurs in the gel and the
      concentration of calcium ion changes periodically. Since the chelates between
      phosphoric groups and the divalent calcium ion, which acts a physical
      crosslinking point, are formed and dissociated periodically, the gel repeats
      swelling and deswelling autonomously.

PMID- 16283709
TI  - DNA-responsive hydrogels that can shrink or swell.
AB  - Molecule-responsive hydrogels are reputed to be smart materials because of their
      unique properties. We recently reported that hydrogels containing directly
      grafted single-stranded (ss) DNA or ssDNA-polyacrylamide conjugate in a semi
      interpenetrating network (semi-IPN) manner that "only shrunk" by the addition of
      ssDNA samples. To date, however, no DNA-responsive hydrogels have been reported
      capable of "swelling" in response to specific DNAs. Smart materials capable of
      both shrinking and swelling in response to specific DNAs would be very useful in
      biochemical and biomedical applications. Here, we show a novel "shrinking or
      swelling" DNA-responsive mechanism. Novel hybrid hydrogels containing rationally
      designed ssDNA as the cross-linker were capable of shrinking or swelling in
      response to ssDNA samples and recognizing a single base difference in the
      samples. On the basis of the results presented in this paper, it is envisioned
      that these novel hybrid hydrogels could function and have potential in
      applications such as DNA-sensing devices and DNA-triggered actuators.

PMID- 16283710
TI  - Novel injectable pH and temperature sensitive block copolymer hydrogel.
AB  - A novel pH and temperature sensitive block copolymer was prepared by adding pH
      sensitive moiety to temperature sensitive block copolymer. This block copolymer
      solution showed a reversible sol-gel transition by a small pH change in the range
      of pH 7.4-8.0 and also by the temperature change in the region of body
      temperature. The very precise molecular weight control of block copolymer and the
      prudential tuning of hydrophilic-hydrophobic balance were needed to control the
      phase diagram. This block copolymer solution forms a gel at 37 degrees C, pH 7.4
      (human body). When the block copolymer solution is at room temperature and pH 8.0
      as a sol state, both the temperature and pH change are needed for the gelation.
      This material can be employed as injectable carriers for hydrophobic drugs and
      proteins, etc. Gelation inside the needle can be prevented by an increase in the
      temperature during injection, because it does not change into the gel form with
      only increasing temperature. This material can be used for even a long guide
      catheter into the body. The block copolymer hydrogel which shows the sol-gel
      transition by the small pH change from pH 8.0 to pH 7.4 has merits in the
      delivery system for protein and cells which show cytotoxicity in acidic (below pH
      6.5) or basic (above pH 8.5) conditions. This block copolymer system could be
      used as a template technology for injectable delivery systems.

PMID- 16283711
TI  - Enzymatic synthesis of chondroitin 4-sulfate with well-defined structure.
AB  - Synthesis of chondroitin sulfate (ChS) with well-defined structure was achieved
      for the first time by hyaluronidase-catalyzed polymerization. N-Acetylchondrosine
      (GlcAbeta(1-->3)GalNAc) oxazoline derivatives sulfated at C4 (1a), C6 (1b), and
      both C4 and C6 (1c) in the GalNAc unit were synthesized as transition state
      analogue substrate monomers for hyaluronidase (HAase) catalysis. Compound 1a was
      effectively polymerized by the enzyme, giving rise to synthetic ChS sulfated
      perfectly at the C4 position in all N-acetylgalactosamine units (Ch4S, 2a) in
      good yields. Molecular weights (Mn) of 2a ranged from 4000 to 18,400, which were
      controlled by varying reaction conditions. Compounds 1b and 1c were not catalyzed
      by the enzyme, affording the corresponding disaccharides through the oxazoline
      ring-opening without formation of polysaccharides.

PMID- 16283712
TI  - Two-dimensional (2D) DNA crystals assembled from two DNA strands.
AB  - Sequence symmetry has been used to simplify the design of a DNA double-crossover
      (DX) molecule. The resulting DX molecule can self-assemble into two-dimensional
      (2D) crystalline arrays, but only requires two instead of otherwise four
      different DNA strands.

PMID- 16283714
TI  - Influence of chain length and polymer concentration on the gelation of (amidated)
      low-methoxyl pectin induced by calcium.
AB  - The gelation of low-methoxyl pectin (LMP) induced by addition of Ca2+ was studied
      by measuring the storage modulus as a function of temperature during cooling.
      Samples with different molar masses were prepared by mechanical degradation. The
      effect of the molar mass and the pectin concentration on the gelation properties
      was investigated. The effect of partial amidation was studied by comparing LMP
      and partially amidated LMP with the same molar mass and degree of methylation.
      The results are compared to those from a model developed for Ca2+-induced pectin
      gelation, and good agreement is found except at low concentrations and low molar
      masses where the gels are weaker than predicted. At low concentrations intrachain
      bonding weakens the gel, while the presence of small pectin chains weakens the
      gel because it neutralizes binding sites on larger chains.

PMID- 16283713
TI  - Hydroxamic acid-containing hydrogels for nonabsorbed iron chelation therapy:
      synthesis, characterization, and biological evaluation.
AB  - Iron overload is a severe clinical condition and can be largely prevented by the
      use of iron-specific chelating agents. A successful iron chelator needs to be
      orally active, nontoxic, and selective. In this study, hydrogels containing
      pendant hydroxamic acid groups have been synthesized as potential nonabsorbed
      chelators for iron in the gastrointestinal tract. The synthetic method employed
      to introduce hydroxamic acid groups to polymer chains involved reaction of
      polymer gels based on N-acryloxysuccinimide, acryloyl chloride, and (2
      hydroxyethyl)acrylate monomers with hydroxylamine. These hydroxamic acid
      functionalized polymer gels swell favorably in water and effectively sequester
      iron. In vitro iron-binding properties of these hydrogels were evaluated from
      their binding isotherms by use of iron(II) alone and in the presence of other
      competing metal ions. These polymers bind iron over a broad pH range. The iron
      binding properties of the polymers were found to depend on the concentration of
      hydroxamate groups on polymer chains. The in vivo iron-binding efficacy of the
      polymers was evaluated in rat as the animal model. The polymers prevented an
      increase in serum hemoglobin and hematocrit levels in the animals, thus
      suggesting the prevention of systemic absorption of dietary iron from the
      gastrointestinal tract. The animals also maintained normal body weight during the
      treatment period, indicating the absence of any apparent toxicity associated with
      these polymers.

PMID- 16283716
TI  - Water sorption studies of hybrid biofiber-reinforced natural rubber
      biocomposites.
AB  - Hybrid biofibers (sisal and oil palm) were incorporated into natural rubber
      matrix. The water absorption characteristics of the composites were evaluated
      with reference to fiber loading. The influence of temperature on water sorption
      of the composites is also analyzed. Moisture uptake was found to be dependent on
      the properties of the biofibers. The mechanism of diffusion in the gum sample was
      found to be Fickian in nature, while in the loaded composites, it was non
      Fickian. Sisal and oil palm fibers were subjected to different treatments such as
      mercerization and silanation. The effect of chemical modification on moisture
      uptake was also analyzed. Chemical modification was seen to decrease the water
      uptake in the composites. The thermodynamic parameters of the sorption process
      were also evaluated. Activation energy was found to be maximum for the gum
      sample.

PMID- 16283715
TI  - Oligonucleotide structure influences the interactions between cationic polymers
      and oligonucleotides.
AB  - We examined the effect of oligodeoxynucleotide (ODN) structure on the
      interactions between cationic polymers and ODNs. Unstructured and hairpin
      structured ODNs were used to form complexes with the model cationic polymer, poly
      L-lysine (pLL), and the characteristics of these polymer-ODN interactions were
      subsequently examined. We found that hairpin structured ODNs formed complexes
      with pLL at slightly lower pLL:ODN charge ratios as compared to unstructured ODNs
      and that, at high charge ratios, greater fractions of the hairpin ODNs were
      complexed, as measured by dye exclusion. The dissociation of pLL-ODN interactions
      was tested further by challenge with heparin, which induced complex disruption.
      Both the kinetics and heparin dose response of ODN release were determined. The
      absolute amount and the kinetic rate of ODN release from the complexes of pLL and
      unstructured ODN were greater, as compared to hairpin ODNs. Our results therefore
      highlight the role of ODN structure on the association-dissociation behavior of
      polymer-ODN complexes. These findings have implications for the selection of ODN
      sequences and design of polymeric carriers used for cellular delivery of ODNs.

PMID- 16283717
TI  - Calorimetric and structural investigation of the interaction between bovine serum
      albumin and high molecular weight dextran in water.
AB  - This work studies specific interactions between a small globular protein and a
      highly flexible, branched polysaccharide using differential scanning calorimetry
      (DSC), circular dichroism (CD), fluorescence, and turbidimetry measurements. It
      uses the system water/bovine serum albumin (BSA)/dextran (D 2000) as a model.
      Dextran molecules are able to form interpolymeric complexes with BSA in water at
      both low and high temperatures if the polysaccharide is in excess and if the
      protein exists in its associated state. It leads to a partial destabilization of
      the secondary and tertiary structures of the protein and an additional exposure
      of the hydrophobic tryptophan residues to the surface of globule. If the total
      concentration of biopolymers in the mixture is high enough, the stability of the
      protein molecules with respect to unfolding and thermoaggregation is
      significantly decreased as a result of an increase in the protein hydrophobicity.

PMID- 16283718
TI  - Synthesis, characterization, and evaluation as transfection reagents of double
      hydrophilic star copolymers: effect of star architecture.
AB  - Five star polymers of the ionizable hydrophilic 2-(dimethylamino)ethyl
      methacrylate (DMAEMA) and the nonionic hydrophilic methoxy hexa(ethylene glycol)
      methacrylate (HEGMA) were prepared by group transfer polymerization (GTP) using
      ethylene glycol dimethacrylate (EGDMA) as coupling agent. In particular, four
      isomeric star copolymers, one heteroarm, two star block and one statistical star,
      with 90% mol DMAEMA and 10% mol HEGMA, plus one star homopolymer of DMAEMA with
      degrees of polymerization of the arms equal to 20 were synthesized. The polymers
      were characterized in terms of their molar masses (MMs) and compositions using
      gel permeation chromatography (GPC) and proton nuclear magnetic resonance (1H
      NMR) spectroscopy, respectively. The hydrodynamic diameters in water indicated
      some aggregation for all the star polymers except for the statistical copolymer
      star, while the pK values of the DMAEMA units were around 7 for all star
      polymers. All the star polymers were evaluated for their ability to transfect
      human cervical HeLa cancer cells with the modified plasmid pRLSV40 bearing the
      enhanced green fluorescent protein (EGFP) as the reporter gene. All four star
      copolymers showed decreased toxicity compared to that of the DMAEMA star
      homopolymer for the same amounts of star polymer tested. The star block copolymer
      with outer DMAEMA blocks exhibited the highest overall transfection efficiency,
      11%, compared to that of all the star polymers examined in this study. This
      efficiency was the same as that of the commercially available transfection
      reagent SuperFect.

PMID- 16283719
TI  - Formation of collagen-glycosaminoglycan blended nanofibrous scaffolds and their
      biological properties.
AB  - The development of blended collagen and glycosaminoglycan (GAG) scaffolds can
      potentially be used in many soft tissue engineering applications since the
      scaffolds mimic the structure and biological function of native extracellular
      matrix (ECM). In this study, we were able to obtain novel nanofibrous collagen
      GAG scaffolds by electrospinning collagen blended with chondroitin sulfate (CS),
      a widely used GAG, in a mixed solvent of trifluoroethanol and water. The
      electrospun collagen-GAG scaffold with 4% CS (COLL-CS-04) exhibited a uniform
      fiber structure with nanoscale diameters. A second collagen-GAG scaffold with 10%
      CS consisted of smaller diameter fibers but exhibited a broader diameter
      distribution due to the different solution properties in comparison with COLL-CS
      04. After cross-linking with glutaraldehyde vapor, the collagen-GAG scaffolds
      became more biostable and were resistant to collagenase degradation. This is
      evidently a more favorable environment allowing increased proliferation of rabbit
      conjunctiva fibroblast on the scaffolds. Incorporation of CS into collagen
      nanofibers without cross-linking did not increase the biostability but still
      promoted cell growth. The potential of applying the nanoscale collagen-GAG
      scaffold in tissue engineering is significant since the nanodimension fibers made
      of natural ECM mimic closely the native ECM found in the human body. The high
      surface area characteristic of this scaffold may maximize cell-ECM interaction
      and promote tissue regeneration faster than other conventional scaffolds.

PMID- 16283720
TI  - Morphology of actin assemblies in response to polycation and salts.
AB  - F-actins are semi-flexible polyelectrolytes and can be assembled into a large
      polymer-actin complex with polymorphism through electrostatic interaction with
      polycations. This study investigates the structural phase behavior and the growth
      of polymer-actin complexes in terms of its longitudinal and lateral sizes in
      various polycation and KCl concentrations for a constant actin concentration. Our
      results show that the longitudinal growth and lateral growth of polymer-actin
      complexes, initiated by a common nucleation process, are dominated by different
      factors in subsequent growth process. This induces the structural polymorphism of
      polymer-actin complexes. Major factors to influence the polymorphism of polymer
      actin complexes in polyelectrolyte systems have been discussed. Our results
      indicate that the semiflexible polyelectrolyte nature of F-actins is important
      for controlling the morphology and growth of actin architectures in cells.

PMID- 16283721
TI  - Statistical studies of flexible nonhomogeneous polypeptide chains.
AB  - Unfolded proteins attract increasing attention nowadays because of the
      accumulation of experimental evidence that they play an important role in
      different biological processes. Therefore, studies of various statistical
      properties of flexible protein-like polypeptide chains are becoming increasingly
      important as well. This paper presents distributions (histograms) of distances
      between atoms of titratable residues for flexible polypeptide chains with various
      residue compositions and with the hard-spheres potential taken into
      consideration. The factors influencing the parameters of the obtained histograms
      have been identified and analyzed. It was found that the sensitivity of the
      distributions with respect to the internal structure of intermediate residues
      increases with the number of residues between the considered charged residues. It
      was shown that branching at C(beta) atoms of the side chains of the intermediate
      residues is among the most considerable factors influencing the shape of the
      distance distribution and the average distance between atoms in flexible chains.
      Despite the model simplicity, the results of the calculations can be applied for
      systems with other types of interactions presented, and this was demonstrated for
      the charge-charge interactions. In particular, it was shown that those
      interactions have a significant effect on distances between the unlike charges,
      while such an effect for the like charges is much less pronounced. The comparison
      of predictions made on the basis of the presented calculations to some
      experimental data is also given, and possible applications of the theoretical
      concept described in the paper are discussed.

PMID- 16283722
TI  - Using self-consistent-field theory to understand enhanced steric stabilization by
      casein-like copolymers at low surface coverage in mixed protein layers.
AB  - We present a statistical mechanical approach to predicting the properties of
      mixed copolymer layers using the Scheutjens-Fleer self-consistent-field theory.
      Our model copolymers are based on the primary structures of the major bovine
      casein monomers, alpha(s1)-casein and beta-casein. Numerical calculations have
      been carried out to determine the polymer segment density profiles at an isolated
      hydrophobic surface and the interaction forces as a pair of polymer-coated
      surfaces is brought to close interlayer separation. For a copolymer model
      containing hydrophilic and hydrophobic segments, we show how the steric
      stabilizing capacity of a casein-like macromolecule at very low surface coverage
      is enhanced in the presence of a thin dense layer of shorter tethered amphiphilic
      chains. Using a more refined protein model, which also distinguishes between the
      charged and uncharged hydrophilic segments along the chain, we clearly
      demonstrate that the enhanced steric repulsion from beta-casein exceeds that from
      alpha(s1)-casein. These calculations explain how the replacement of just a few
      percent of beta-lactoglobulin by casein can inhibit the heat-induced thickening
      and flocculation behavior observed experimentally with some whey protein
      stabilized oil-in-water emulsions.

PMID- 16283723
TI  - Cytochrome c superstructure biocomposite nucleated by gold nanoparticle: thermal
      stability and voltammetric behavior.
AB  - The thermal stability of cytochrome c (cyt c) after Au-nanoparticle-directed
      association has been studied by various spectroscopic (electronic absorption,
      resonance Raman, and circular dichroism) and electrochemical methods. The results
      show that the thermal stability of the Au-cyt c superstructure biocomposite
      formed by the electrostatic and hydrophobic interactions among the associated
      proteins increases significantly. It is mainly caused by strong hydrophobicity of
      the associated cyt c in Au-cyt c superstructure at high temperature, which
      results from the compact secondary structure and the packing of hydrophobic side
      chains around the Trp 59 and heme. In addition, the formation of bis-His
      configuration of heme is facilitated by the tightly self-associated state of cyt
      c in the Au-cyt c superstructure. The electrostatic coupling of the opposite
      charges among shells of the adsorbed proteins due to the formation of the
      superstructure biocomposite can reduce repulsions among the same charges in
      protein. These factors are also important for enhancing the stability of the
      associated cyt c. Furthermore, the voltammetric behavior of Au-cyt c at DNA
      modified glassy carbon electrode has been investigated for extending the
      application of Au-cyt c.

PMID- 16283724
TI  - Alterations in physical cross-linking modulate mechanical properties of two-phase
      protein polymer networks.
AB  - Physically cross-linked protein-based materials possess a number of advantages
      over their chemically cross-linked counterparts, including ease of processing and
      the ability to avoid the addition or removal of chemical reagents or unreacted
      intermediates. The investigations reported herein sought to examine the nature of
      physical cross-links within two-phase elastin-mimetic protein triblock copolymer
      networks through an analysis of macroscopic viscoelastic properties. Given the
      capacity of solution processing conditions, including solvent type and
      temperature to modulate the microstructure of two-phase protein polymer networks,
      viscoelastic properties were examined under conditions in which interphase block
      mixing had been either accentuated or diminished during network formation.
      Protein networks exhibited strikingly different properties in terms of elastic
      modulus, hysteresis, residual deformability, and viscosity in response to
      interdomain mixing. Thus, two-phase protein polymer networks exhibit tunable
      responses that extend the range of application of these materials to a variety of
      tissue engineering applications.

PMID- 16283725
TI  - Simultaneous and in situ analysis of thermal and volumetric properties of starch
      gelatinization over wide pressure and temperature ranges.
AB  - A method for simultaneous and in situ analysis of thermal and volumetric
      properties of starch gelatinization from 0.1 to 100 MPa and from 283 to 430 K is
      described. The temperature of a very sensitive calorimetric detector containing a
      starch-water emulsion at a selected pressure is programmed to rise at a slow
      rate; volume variations are performed automatically to keep the selected pressure
      constant while the heat exchange rate and the volume are recorded. The method is
      demonstrated with a novel investigation of pressure effects on a sequence of
      three phase transitions in an aqueous emulsion of wheat starch (56 wt % water).
      The volume changes during the main endothermic transition (M), associated with
      melting of the crystalline part of the starch granules and a helix-coil
      transformation in amylopectin, but also with an important swelling, were
      separated into a volume increase associated with swelling and a volume decrease
      associated with the transition itself. Thermodynamic parameters for this
      transition together with their pressure dependencies have been obtained from four
      independent experiments at each pressure. The data are thermodynamically
      consistent, but are poorly described by the Clapeyron equation. The negative
      volume change of the slow exothermic transition (A) appearing just after the main
      endothermic transition (M) is small, spread out over a wide temperature interval,
      and occurs at higher temperatures with increasing pressures. This transition is
      probably associated with reassociation of the unwound helixes of amylopectin with
      parts of amylopectin molecules other than their original helix duplex partner.
      The positive volume change of the high-temperature, endothermic transition (N)
      with a small enthalpy change is probably associated with a nematic-isotropic
      transformation ending the formation of a homogeneous SOL phase (in the sense of
      Flory), and is also pushed to higher temperatures with increasing pressures.
      Knowledge of the state of wheat starch as a function of pressure and temperature
      is important in extruder processing. The data also provide a basis for the
      elliptic phase diagram for starch gelatinization. The method is easily adapted to
      determine similar data for other macromolecular materials.

PMID- 16283727
TI  - Direct force measurements between cellulose surfaces and colloidal silica
      particles.
AB  - The interaction of cellulose layers with colloidal silica particles was
      investigated by direct force measurements with the atomic force microscope (AFM).
      Upon approach, repulsive forces were found between the negatively charged silica
      particles and the cellulose surface. The forces were interpreted quantitatively
      in terms of electrostatic interactions due to overlap of diffuse layers
      originating from negatively charged carboxylic groups on the cellulose surface.
      The diffuse layer charge density of cellulose was estimated to be 0.80 mC/m2 at
      pH 9.5 and 0.21 mC/m2 at pH 4. The forces upon retraction are characterized by
      molecular adhesion events, whereby individual cellulose chains desorb from the
      probe surface. The retraction profiles are dominated by well-defined force
      plateaus, which correspond to single-chain desorption forces of 35-42 pN. We
      surmise that adsorption of cellulose to probe surfaces is dominated by
      nonelectrostatic forces, probably originating from hydrogen bonding.
      Electrostatic contributions to desorption force could be detected only at high
      pH, where the silica surface is highly charged.

PMID- 16283726
TI  - L-Phe end-capped poly(L-lactide) as macroinitiator for the synthesis of poly(L
      lactide)-B-poly(L-lysine) block copolymer.
AB  - A poly(L-lactide)-b-poly(Nepsilon-(Z)-L-lysine) (PLLA-b-PZLys) block copolymer
      was synthesized through the ring-opening polymerization of Nepsilon-(Z)-lysine-N
      carboxyanhydride using L-Phe-terminated PLLA as a macroinitiator. The L-Phe
      terminated PLLA was prepared through a novel three-step process. First, the
      hydroxyl-terminated PLLA was synthesized through the ring-opening polymerization
      of L-lactide initiated by n-butanol under the existence of tin(II)
      ethylhexanoate. Subsequently, the complete capping of the hydroxyl end group of
      PLLA with BOC-L-Phe was achieved by using a mixed anhydride of BOC-L-Phe under
      the catalysis of 4-(1-pyrrolidinyl) pyridine. Finally, the free amino end group
      was obtained by removal of the t-butoxycarbonyl group through trifluoroacetic
      acid treatment under anhydrous condition. All these treatments were conducted
      under mild conditions, thus avoiding the breakdown of the PLLA backbone. Poly(L
      lactide)-b-poly(L-lysine) block copolymer was produced after deprotection
      treatment of PLLA-b-PZLys. The structure of the block copolymer was confirmed by
      1H NMR, IR, and GPC. Adjustment of the ratio of the NCA monomer to the
      macroinitiator could control the chain length of the PLys block.

PMID- 16283728
TI  - Preparation and mechanical properties of chitosan/carbon nanotubes composites.
AB  - Biopolymer chitosan/multiwalled carbon nanotubes (MWNTs) nanocomposites have been
      successfully prepared by a simple solution-evaporation method. The morphology and
      mechanical properties of the chitosan/MWNTs nanocomposites have been
      characterized with field emission scanning electron microscopy (SEM), bright
      field transmission electron microscopy (TEM), optical microscopy (OM), wide-angle
      X-ray diffraction (XRD), and tensile as well as nanoindentation tests. The MWNTs
      were observed to be homogeneously dispersed throughout the chitosan matrix. When
      compared with neat chitosan, the mechanical properties, including the tensile
      modulus and strength, of the nanocomposites are greatly improved by about 93% and
      99%, respectively, with incorporation of only 0.8 wt % of MWNTs into the chitosan
      matrix.

PMID- 16283729
TI  - Control of the chemical cross-linking of gelatin by a thermosensitive polymer:
      example of switchable reactivity.
AB  - Chemical cross-linking of gelatin is achieved using a thermosensitive reactive
      copolymer based on N-isopropylacrylamide (NIPAM). The copolymer bears 5 mol %
      acrylic acid units which form amide bonds with the amino groups of gelatin in the
      presence of a water-soluble carbodiimide. The cross-linking reaction occurs only
      below the LCST congruent with 34 degrees C (lower critical solution temperature),
      i.e., when the copolymer is in the coil conformation. Above the LCST the
      copolymer adopts a globule conformation and its ability to react with gelatin is
      drastically reduced. By setting the temperature above or below the LCST it is
      possible to switch off or on the reactivity of the system and control the
      gelation process. The switch temperature can be set at the desired value by
      adjusting the composition of the thermosensitive copolymer.

PMID- 16283730
TI  - Swelling behavior and morphological evolution of mixed gelatin/silk fibroin
      hydrogels.
AB  - Mixed protein-based hydrogels have been prepared by blending gelatin (G) with
      amorphous Bombyx mori silk fibroin (SF) and promoting beta-crystallization of SF
      via subsequent exposure to methanol or methanol/water solutions. The introduction
      of beta crystals in SF serves to stabilize the hydrogel network and extend the
      solidlike behavior of these thermally responsive materials to elevated
      temperatures beyond the helix-->coil (h-->c) transition of G. In this work, we
      investigate the swelling and protein release kinetics of G/SF hydrogels varying
      in composition at temperatures below and above the G h-->c transition. At 20
      degrees C, G and G-rich mixed hydrogels display evidence of moderate swelling
      with negligible mass loss in aqueous solution, resulting in porous polymer
      matrixes upon solvent removal according to electron microscopy. When the solution
      temperature is increased beyond the G h-->c transition to body temperature (37
      degrees C), these gels exhibit much higher swelling with considerable mass loss
      due to dissolution and release of G. The extent to which these properties respond
      to temperature decreases systematically with increasing SF content. The unique
      temperature- and composition-dependent properties of G/SF hydrogels dictate the
      efficacy of these novel materials as stimuli-responsive delivery vehicles.

PMID- 16283731
TI  - Organo hydrogel hybrids. Formation of reservoirs for protein delivery.
AB  - A biodegradable organo hydrogel hybrid material is presented, which is formed
      through the water uptake of a phosphoryl choline zwitterionomer (PC ionomer). The
      water uptake and subsequent swelling is induced by the phosphoryl choline (PC)
      end group functionality. The nonfunctional poly(trimethylene carbonate) is
      hydrophobic and as such does not absorb any water. Disks of the PC ionomer showed
      significant water uptake, typically above 90 wt % when fully swollen. This high
      water uptake triggered us to utilize the material for drug and protein loading
      and subsequent release. Fluorescein and fluorescein-labeled proteins were used as
      simple models for the loading and release characteristics of the material which
      was studied by fluorescence spectroscopy. The rate of release of the loaded
      molecules was compared, and it was shown that the release rate was similar for
      FITC and insulin but slightly slower for albumin. These results suggest that the
      PC ionomer may be used as a biodegradable and low elastic modulus material with
      an additional drug and/or protein release capacity. Such materials are of
      particular interest for use in a variety of applications in vivo, for example as
      drug eluting stents.

PMID- 16283732
TI  - An investigation of the divergence of major ampullate silk fibers from Nephila
      clavipes and Argiope aurantia.
AB  - The major ampullate fiber of both Nephila clavipes and Argiope aurantia is
      composed of two different proteins, MaSp1 and MaSp2. Each of these proteins has a
      highly conserved pattern of silk-associated amino acid motifs. The GPGXX motif is
      the only source of proline and is unique to MaSp2. On the basis of the percent of
      proline, Nephila clavipes major ampullate silk was calculated to consist of 19%
      MaSp2 and 81% MaSp1, while Argiope aurantia was calculated to have a
      significantly higher MaSp2 content of 59% with MaSp1 comprising the remaining
      41%. To investigate the functional implications of the difference in protein
      composition, major ampullate silk fibers from Nephila clavipes and Argiope
      aurantia were mechanically tested and compared. Stress-strain curves produced
      from polynomial regression show that the two significant differences between
      major ampullate silk fibers from Nephila clavipes and Argiope aurantia are the
      average peak load stress and Young's modulus, with Argiope higher for both.

PMID- 16283733
TI  - New process to form a silk fibroin porous 3-D structure.
AB  - A new process to form fibroin spongy porous 3-D structure is reported herein. The
      process involves freezing and thawing fibroin aqueous solution in the presence of
      a small amount of an organic solvent. The process requires no freeze-drying,
      chemical cross-linking, or the aid of other polymeric materials. The solvent
      concentration, fibroin concentration, freezing temperature, and freezing duration
      affect the sponge formation, its porous structure, and its mechanical properties.
      Measurements by XRD and FTIR indicate that silk I and silk II crystalline
      structures exist in the fibroin sponge and that the secondary structure of
      fibroin is transformed to a beta-sheet from a random coil during this process.
      The tensile strength decreased slightly, but the fibroin sponge showed no
      deformation after autoclaving. Therefore, the fibroin sponge was sterilized using
      an autoclave. For 3 weeks, MC3T3 cells proliferated in the sterilized fibroin
      sponge. The fibroin sponge formed by this new process is applicable as a tissue
      engineering scaffold because it is formed from biocompatible pure silk fibroin
      and offers both porous structure and mechanical properties that are suitable for
      cell growth and handling.

PMID- 16283734
TI  - Jamming and gelation of dense beta-casein micelle suspensions.
AB  - The rheology of dense suspensions of beta-casein micelles is investigated at pH
      6. For a given temperature, the viscosity increases dramatically at a critical
      concentration (Cc) of about 100 g/L due to jamming of the micelles. For a given
      concentration close to and above Cc, the viscosity of dense suspensions decreases
      strongly with increasing temperature because Cc increases. The suspensions show
      weak shear thickening followed by strong shear thinning. At lower pH, that is,
      closer to the isoelectric point, spontaneous gelation is observed, which is
      favored by lowering the temperature and addition of sodium polyphosphate. The
      gelation process is studied at pH 5.5 by rheology and light scattering.

PMID- 16283735
TI  - Physical characterization of blends of poly(D-lactide) and LHRH (a leuprolide
      decapeptide analog).
AB  - Stereocomplexes between poly(D-lactide) (PDLA) and poly(L-lactide) (PLLA) have
      been extensively studied, including, in recent years, several reports on the
      stereocomplexation of PDLA with small molecules such as peptides. Here, the
      possible complexation between PDLA and luteinizing hormone releasing hormone
      (LHRH), a l-configured decapeptide, is considered for which several observations
      were made: (1) in calorimetry an additional endothermic peak appears at a lower
      temperature than the melting temperature of pure PDLA; (2) in Raman analyses a
      band splitting of the C=O stretching mode (not present in pure PDLA) shows up;
      (3) in X-ray diffraction, however, no change is observed after mixing the two
      species, indicating no crystal structure modification (and the absence of any
      stereocomplex crystal structure). The calorimetric double melting peak is merely
      explained by the presence of two distinct morphological forms of PDLA, whereas
      the spectroscopic band splitting can be due to simple differences of
      crystallinity. From these observations it is concluded that the LHRH modifies the
      crystallization of PDLA without, however, the formation of a stereocomplex.

PMID- 16283736
TI  - Methoxy poly(ethylene glycol)-block-poly(delta-valerolactone) copolymer micelles
      for formulation of hydrophobic drugs.
AB  - Six amphiphilic diblock copolymers based on methoxy poly(ethylene glycol) (MePEG)
      and poly(delta-valerolactone) (PVL) with varying hydrophilic and hydrophobic
      block lengths were synthesized via a metal-free cationic polymerization method.
      MePEG-b-PVL copolymers were synthesized using MePEG with Mn = 2000 or Mn = 5000
      as the macroinitiator. 1H NMR and GPC analyses confirmed the synthesis of diblock
      copolymers with relatively narrow molecular weight distributions (Mn/Mw = 1.05
      1.14). DSC analysis revealed that the melting temperatures (Tm) of the copolymers
      (47-58 degrees C) approach the Tm of MePEG as the PVL content is decreased. MePEG
      b-PVL copolymer aggregates loaded with the hydrophobic anti-cancer drug
      paclitaxel were found to have effective mean diameters ranging from 31 to 970 nm
      depending on the composition of the copolymers. A MePEG-b-PVL copolymer of a
      specific composition was found to form drug-loaded micelles of 31 nm in diameter
      with a narrow size distribution and improve the apparent aqueous solubility of
      paclitaxel by more than 9000-fold. The biological activity of paclitaxel
      formulated in the MePEG-b-PVL micelles was confirmed in human MCF-7 breast and
      A2780 ovarian cancer cells. Furthermore, the biocompatibility of the copolymers
      was established in CHO-K1 fibroblast cells using a cell viability assay. The in
      vitro hydrolytic and enzymatic degradation of the micelles was also evaluated
      over a period of one month. The present study indicates that the MePEG-b-PVL
      copolymers are suitable biomaterials for hydrophobic drug formulation and
      delivery.

PMID- 16283737
TI  - Effects of beta-cyclodextrin addition and temperature on the modulation of
      hydrophobic interactions in aqueous solutions of an associative alginate.
AB  - Novel information about the effects of beta-cyclodextrin (beta-CD) addition and
      temperature on structural and rheological features of semidilute solutions of
      alginate and its hydrophobically modified analogue (HM-alginate) is given.
      Enhanced turbidity is observed for the HM-alginate solutions at high levels of
      beta-CD addition and low temperatures. The viscosity results revealed cross
      linking of the alginate chains at high beta-CD concentrations and low
      temperatures. Rheological results for the HM-alginate solutions demonstrated that
      high levels of beta-CD addition and elevated temperatures promoted decoupling of
      the hydrophobic polymer-polymer associations via inclusion complex formation
      between beta-CD cavities and the hydrophobic side chains of the polymer. Analysis
      of small-angle neutron scattering (SANS) results from HM-alginate solutions in
      the presence of beta-CD suggested that the polymer chains are locally stretched
      at all of the considered levels of beta-CD and temperatures. The SANS results
      revealed association structures. The general picture that emerges is that beta-CD
      addition and temperature can be combined to tune the intensity of the hydrophobic
      interactions and to cross-link the unmodified alginate.

PMID- 16283738
TI  - Structural characteristics of hydrolysates of proteins from extracted sunflower
      flour at the air-water interface.
AB  - The structural and topographical characteristics of a sunflower protein isolate
      (SPI) and its hydrolysates at different degrees of hydrolysis (DH = 5.62%, 23.5%,
      and 46.3%) spread at the air-water interface at pH 7 and 20 degrees C were
      determined from pi-A isotherms coupled with Brewster angle microscopy (BAM). The
      structural characteristics of SP hydrolysate spread monolayers depend on the
      degree of hydrolysis. We observed a significant shift of the pi-A(APPARENT)
      isotherms toward lower molecular areas as the degree of hydrolysis (DH)
      increased. This phenomenon was attributed to spreading of the protein at the
      interface, especially at DH 46.3%. A change in the monolayer structure was
      observed at a surface pressure of 12-15 mN/m. At a microscopic level, the
      heterogeneous monolayer structures visualized near the monolayer collapse and
      during the monolayer expansion proved the existence of large regions of protein
      aggregates. Reflectivity increased with surface pressure and was a maximum at the
      monolayer collapse. The monolayer thickness decreased as the degree of hydrolysis
      increased. These phenomena explain the poor functional properties for the
      formation and stabilization of a dispersion (emulsion or foam) of protein
      hydrolysates at high degrees of hydrolysis.

PMID- 16283740
TI  - Analysis of the conserved N-terminal domains in major ampullate spider silk
      proteins.
AB  - Major ampullate silk, also known as dragline silk, is one of the strongest
      biomaterials known. This silk is composed of two proteins, major ampullate
      spidroin 1 (MaSp1) and major ampullate spidroin 2 (MaSp2). Only partial cDNA
      sequences have been obtained for these proteins, and these sequences are toward
      the C-terminus. Thus, the N-terminal domains have never been characterized for
      either protein. Here we report the sequence of the N-terminal region of major
      ampullate silk proteins from three spider species: Argiope trifasciata,
      Latrodectus geometricus, and Nephila inaurata madagascariensis. The amino acid
      sequences are inferred from genomic DNA clones. Northern blotting experiments
      suggest that the predicted 5' end of the transcripts are present in fibroin mRNA.
      The presence of more than one Met codon in the N-terminal region indicates the
      possibility of translation of both a long and a short isoform. The size of the
      short isoform is consistent with the published, cDNA based, N-terminal sequence
      found in flagelliform silk. Analyses comparing the level of identity of all known
      spider silk N-termini show that the N-terminus is the most conserved part of silk
      proteins. Two DNA sequence motifs identified upstream of the putative
      transcription start site are potential silk fibroin promoter elements.

PMID- 16283739
TI  - Cross-sectional analysis of the polysaccharide composition in cellulosic fiber
      materials by enzymatic peeling/high-performance capillary zone electrophoresis.
AB  - A combined enzymatic, chemical, and analytical approach was used to determine the
      cross-sectional carbohydrate composition in cellulosic fibers. The outer surface
      of cellulosic fibers was enzymatically removed layer-by-layer with precise
      quantitative control, and the monosaccharides in the peelings were subsequently
      analyzed by high-performance capillary electrophoresis (HPCE) after precolumn
      derivatization with a UV label. This method was applied to dissolving pulps and
      regenerated cellulose fibers, with special emphasis on the cross-sectional
      distribution of hemicelluloses. Commercially available enzyme solutions were
      used, resulting in a reproducible peeling. Significant differences were found in
      the hemicellulose distribution across the fiber of different dissolving pulps,
      dependent on both natural source (beech or spruce) and preparation process
      (acidic sulfite cook or prehydrolysis kraft cook). Among the dissolving pulps,
      beech prehydrolysis kraft pulp showed the highest enrichment of surface xylan.
      Similar, albeit smaller, differences were noticed between various regenerated
      fibers (viscose, viscose Modal, and Lyocell): a thin hemicellulose-rich outermost
      layer was found in all the regenerated fibers studied.

PMID- 16283741
TI  - Characterization of cellulose whiskers and their nanocomposites by atomic force
      and electron microscopy.
AB  - The aim of this work was to compare and explore electron microscopy and atomic
      force microscopy (AFM) for structure determination of cellulose whiskers and
      their nanocomposite with poly(lactic acid). From conventional bright-field
      transmission electron microscopy (TEM) it was possible to identify individual
      whiskers, which enabled determination of their sizes and shape. AFM overestimated
      the width of the whiskers due to the tip-broadening effect. Field emission
      scanning electron microscopy (FESEM) allowed for a quick examination giving an
      overview of the sample; however, the resolution was considered insufficient for
      detailed information. Ultramicrotomy of nanocomposite films at cryogenic
      temperatures enabled detailed inspection of the cellulose whiskers in the
      poly(lactic acid) matrix by AFM. FESEM applied on fractured surfaces allowed
      insight into the morphology of the nanocomposite, although rather restricted due
      to the metal coating and limited resolution. Detailed information was obtained
      from TEM; however, this technique required staining and suffered in general from
      limited contrast and beam sensitivity of the material.

PMID- 16283742
TI  - Evaluation of hyperbranched poly(amino ester)s of amine constitutions similar to
      polyethylenimine for DNA delivery.
AB  - New hyperbranched poly(amino ester)s were synthesized via A3 + 2BB'B' ' approach,
      represented by the Michael addition polymerization of trimethylol-propane
      triacrylate (TMPTA) (A3-type monomers) with a double molar 1-(2
      aminoethyl)piperazine (AEPZ) (BB'B''-type monomer) performed in chloroform at
      ambient temperature. The results obtained by in situ monitoring the
      polymerization using NMR and MS indicated that hyperbranched poly(TMPTA1-AEPZ2)
      was formed via a A(B'B'')2 intermediate, and the B' ' (the formed 2 degrees
      amine) was kept intact in the reaction. Therefore, poly(TMPTA1-AEPZ2) contained
      secondary and tertiary amines in the core and primary amines in the periphery
      similar to polyethylenimine (PEI). The chemistry of protonated poly(TMPTA1-AEPZ2)
      was further confirmed by 13C NMR, and the molecular weight, the radius of
      gyration (Rg), and the hydrodynamic radius (Rh) were determined using GPC, small
      angle X-ray scattering (SAXS), and laser dynamic light scattering (LDLS),
      respectively. The ratio of Rg/Rh of ca. 1.1 verified the hyperbranched structure.
      Protonated hyperbranched poly(TMPTA1-AEPZ2) is degradable and less cytotoxic as
      compared with PEI (25 K). Gel electrophoresis reflected that stable complexes
      could be formed from protonated hyperbranched poly(TMPTA1-AEPZ2) and DNA, and the
      size and xi-potential of the complexes were characterized. Remarkably, protonated
      hyperbranched poly(TMPTA1-AEPZ2) showed transfection efficiency comparable to PEI
      (25 k) for in vitro DNA delivery.

PMID- 16283743
TI  - Glycosaminoglycan composition of the large freshwater mollusc bivalve Anodonta
      anodonta.
AB  - In this paper, glycosaminoglycans from the body of the large freshwater mollusc
      bivalve Anodonta anodonta were recovered at about 0.6 mg/g of dry tissue,
      composed of chondroitin sulfate (approximately 38%), nonsulfated chondroitin
      (about 21%), and heparin (41%). This last polysaccharide was found to consist of
      a large percentage (approximately 88%) of a fast-moving species possessing a
      lower molecular mass and sulfate group amount and about 12% of a more sulfated,
      slow-moving component having a greater molecular mass. The chondroitin sulfate
      was composed of approximately 28% of the 6-sulfated disaccharide, 46% of the 4
      sulfated disaccharide, and about 26% of the nonsulfated disaccharide, with a
      charge density value of 0.74. Heparin was subjected to the oligosaccharide
      mapping after treatment with heparinase and then separation of the resulting
      unsaturated oligosaccharides by SAX-HPLC. A heparin sample from Anodonta anodonta
      showed a degree of sulfation similar to that of bovine mucosal heparin because of
      the presence of approximately the same mol % of the trisulfated disaccharide
      (DeltaUA2S(1-->4)-alpha-D-GlcN2S6S), a slight modification of the other
      oligosaccharides, and a significant increase of the disaccharide bearing the
      sulfate group in position 3 of the N-sulfoglucosamine 6-sulfate (-->4)-beta-D
      GlcA(1-->4)-alpha-D-GlcN2S3S6S(1-->) part of the ATIII-binding region. However,
      the anticoagulant activity of mollusc heparin was quite similar to that of
      pharmaceutical grade heparin. The data obtained again emphasize the heterogeneity
      of GAGs from molluscs.

PMID- 16283744
TI  - Synthesis and characterization of biodegradable hyperbranched poly(ester-amide)s
      based on natural material.
AB  - A series of novel AB3-type monomers were prepared from nontoxic natural gallic
      acid and amino acids. These monomers were then melt-polycondensed in the presence
      of MgO as a catalyst via a transesterification process at 170-190 degrees C to
      yield the hyperbranched poly(ester-amide)s bearing terminal acetyl groups. FTIR
      and NMR spectra confirmed the structures of all the monomers and polymers. The
      degrees of branching, estimated from 1H NMR and quantitative 13C NMR spectra,
      were 0.50-0.68. These hyperbranched polymers displayed moderately high molecular
      weights. Hydrolytic and enzymatic degradation studies were carried out in vitro
      at 37.5 degrees C in NaOH hydrotropic solution and in Tris-HCl buffer (pH = 8.6)
      containing proteinase K, respectively. The results indicate that the
      hyperbranched poly(ester-amide)s are degradable hydrolytically as well as
      enzymatically, and the rate of hydrolytic degradation increases with the pH value
      of the solution.

PMID- 16283745
TI  - Kinetics of cold-set diffusion-limited aggregations of denatured whey protein
      isolate colloids.
AB  - The CaCl2-induced cold-set aggregation kinetics of the denatured whey protein
      isolate (WPI) colloids has been investigated under dilute diffusion-limited
      cluster aggregation (DLCA) conditions, using small-angle light scattering. In
      particular, the structure factor, the scattered intensity at zero angle and the
      average radius of gyration have been measured for the aggregating system as a
      function of time. It is found that the fractal dimension of the clusters is df=
      1.85, in the range typical of clusters aggregated under DLCA conditions. The
      aggregation kinetics in this transition region can be described by a power law
      relation in the initial stage of the aggregation, but the exponent of the power
      law is equal to 0.7, i.e., significantly larger than 1/df= 0.54, which is the
      typical value of the DLCA kinetics. Since it is found that the average gyration
      radius of the clusters has reached a value of 80 microm, leading to a cumulative
      volume fraction of clusters equal to 0.25, it is legitimate to expect that the
      process is in the region of transition from aggregation to gelation. This
      confirmed by the fact that, at the later stage of the aggregation, the growth of
      the average cluster size further accelerates with time and eventually becomes
      explosive, leading to gelation. The observed aggregation kinetics has been
      compared with that reported in the literature from DLCA Monte Carlo simulations,
      and a good agreement has been found with the data corresponding to the transition
      region from aggregation to gelation. Numerical simulations using the Smoluchowski
      kinetic model have also been carried out in order to support the experimental
      findings.

PMID- 16283746
TI  - Recognition and selective binding of DNA by ionenes of different charge density.
AB  - The ability of aliphatic ionenes to recognize and bind DNA or poly(methacrylic
      acid) (PMA) in the equimolar mixture of these polyanions was studied by
      fluorescence quenching technique. Within a particular system, the selectivity of
      competitive interactions was shown to be determined by a component with the
      lowest degree of polymerization (DP). Ionene polycations with lowest DP values
      did not exhibit pronounced selectivity in binding DNA or PMA with higher values
      of DP. Increase in ionene DP resulted in a steady increase in selectivity of
      interaction and ultimately in almost exclusive binding of one of the two
      polyanions. The ability of the ionene to recognize and bind DNA in the mixture of
      polyanions was shown not to correlate with the affinity of the ionene to DNA in
      their binary mixture. Although ionenes with a higher charge density exhibited
      preferential binding to PMA, the ionenes with the lowest charge density
      selectively bound DNA.

PMID- 16283747
TI  - Protein/polysaccharide cogel formation based on gelatin and chemically modified
      schizophyllan.
AB  - In the work, aldehyde groups were quantitatively introduced into schizophyllan
      (SPG) side chains through periodate oxidation. The periodate-oxidized SPG (POSPG)
      forms an elastic gel with gelatin. The cogel formation is based on the Schiff
      base reaction between the amino groups of gelatin chains and the aldehyde groups
      of POSPG chains. The POSPG/gelatin cogel has an elastomeric character with a very
      small value of loss tangent. The gelation kinetics and gel properties were
      discussed as a function of POSPG concentration, gelatin concentration, oxidation
      degree, temperature, and pH. This method can be used to design a large variety of
      cogels between SPG and proteins.

PMID- 16283748
TI  - Molecular description of the formation and structure of plasticized globular
      protein films.
AB  - To optimize the properties of plasticized globular proteins films, a clear
      comprehension of the structure and molecular events occurring during film
      formation is required. In this work, the structural organization of beta
      lactoglobulin (beta-lg) films plasticized with diethyelene glycol are
      investigated for the first time during the entire film formation process by
      attenuated total reflectance and transmission infrared spectroscopy. The films
      are made by a common two-step procedure consisting of a first heat treatment (80
      degrees C/30 min) followed by the casting of the film-forming solution for
      dehydration. Heating at 80 degrees C leads to the self-aggregation of the
      proteins with a conversion of regular secondary structures into antiparallel beta
      sheets. The kinetics of the conformational conversion shows that approximately
      10% of the amino acids are involved in beta-sheets after the first step.
      Dehydration induces a further aggregation, with approximately 46% of the amino
      acids involved in beta-sheets in the final film. Water evaporation results in the
      association of the aggregates formed during the heating step. The presence of the
      plasticizer during water removal is essential as it allows specific
      conformational rearrangements into extended beta-sheets and ordering of the
      polypeptide chains. This work underlines that the assembly of building blocks is
      common in beta-lg networks and it emphasizes the widespread occurrence of beta
      structures in synthetic and natural protein networks.

PMID- 16283749
TI  - Structure of model peptides based on Nephila clavipes dragline silk spidroin
      (MaSp1) studied by 13C cross polarization/magic angle spinning NMR.
AB  - To obtain detailed structural information for spider dragline spidroin (MaSp1),
      we prepared three versions of the consensus peptide
      GGLGGQGAGAAAAAAGGAGQGGYGGLGSQGAGR labeled with 13C at six different sites. The
      13C CP/MAS NMR spectra were observed after treating the peptides with different
      reagents known to alter silk protein conformations. The conformation-dependent
      13C NMR chemical shifts and peak deconvolution were used to determine the local
      structure and the fractional compositions of the conformations, respectively.
      After trifluoroacetic acid (solvent)/diethyl ether (coagulant) treatment, the N
      terminal region of poly-Ala (PLA) sequence, Ala8 and Ala10, adopted predominantly
      the alpha-helix with a substantial amount of beta-sheet. The central region,
      Ala15, Ala18, and Leu26, and C-terminal region, Ala31, of the peptide were
      dominated by either 3(1)-helix or alpha-helix. There was no indication of beta
      sheet, although peak broadening indicates that the torsion angle distribution is
      relatively large. After 9 M LiBr/dialysis treatment, three kinds of conformation,
      beta-sheet, random coil, and 3(1)-helix, appeared, in almost equal amounts of
      beta-sheet and random coil conformations for Ala8 and Ala10 residues and
      distorted 3(1)-helix at the central region of the peptide. In contrast, after
      formic acid/methanol and 8 M urea/acetonitrile treatments, all of the local
      structure tends to beta-sheet, although small amounts of random coil are also
      observed. The peak pattern of the Ala Cbeta carbon after 8 M urea/acetonitrile
      treatment is similar to the corresponding patterns of silk fiber from Bombyx mori
      and Samia cynthia ricini. We also synthesized a longer 13C-labeled peptide
      containing two PLA blocks and three Gly-rich blocks. After 8 M urea/acetonitrile
      treatment, the conformation pattern was closely similar to that of the shorter
      peptide.

PMID- 16283751
TI  - Effect of addition of water-soluble chitin on amylose film.
AB  - Amylose films blended with chitosan, which were free from additives such as acid,
      salt, and plasticizer, were prepared by casting mixtures of an aqueous solution
      of an enzymatically synthesized amylose and that of water-soluble chitin (44.1%
      deacetylated). The presence of a small amount of chitin (less than 10%) increased
      significantly the permeability of gases (N2, O2, CO2, C2H4) and improved the
      mechanical parameters of amylose film; particularly, the elastic modulus and
      elongation of the blend films were larger than those of amylose or chitin films.
      No antibacterial activity was observed with either amylose or water-soluble
      chitin films. But amylose films having a small amount of chitin showed strong
      antibacterial action, suggesting a morphological change in water-soluble chitin
      on the film surface by blending with amylose molecule. These facts suggested the
      presence of a molecular complex of amylose and chitosan.

PMID- 16283750
TI  - New aspects of the formation of physical hydrogels of chitosan in a
      hydroalcoholic medium.
AB  - New aspects concerning the mechanism of formation of chitosan physical hydrogels
      without any cross-linking agent were studied. The gelation took place during the
      evaporation of a hydroalcoholic solution of chitosan. We first demonstrated that
      it was possible to form a physical hydrogel from a hydrochloride form of
      chitosan. Chromatographic methods showed that during the gel formation, when the
      initial concentration is over C, the critical concentration of chain
      entanglement, the water and acid used for the solubilization of the polymer were
      both eliminated. This particular situation contributed to decrease the dielectric
      constant of the medium and the apparent charge density of chitosan chains, thus
      inducing the formation of a three-dimensional network through hydrophobic
      interactions and hydrogen bonding. In the gelation process, this step was
      kinetically determining. The speed of evaporation of water and acid were
      determined and different initial conditions were compared. Thus, we investigated
      the influence of: the initial polymer concentration, the nature of the counterion
      and the alcohol, the temperature and the geometry of the reactor. Our results
      allowed us to confirm the existence of a second critical initial concentration C,
      from which the evaporation of water became more difficult. We suggested that C
      corresponded to a reorganization of the solution involving the presence of gel
      precursors. Then, a mechanism of formation of physical hydrogels of chitosan in a
      hydroalcoholic medium could be proposed. For the first time, we demonstrated that
      it was possible to generate physical hydrogels in the presence of various diols,
      which size of the carbonated chain appeared as a limiting factor for the gelation
      process. These physical hydrogels of chitosan are currently used in our
      laboratory for tissue engineering in the treatment of third degree burns with the
      possibility to adapt their mechanical properties from the choice of both the acid
      or the alcohol used.

PMID- 16283752
TI  - Reactive thin polymer films as platforms for the immobilization of biomolecules.
AB  - Spin-coated thin films of poly(N-hydroxysuccinimidyl methacrylate) (PNHSMA) on
      oxidized silicon and gold surfaces were investigated as reactive layers for
      obtaining platforms for biomolecule immobilization with high molecular loading.
      The surface reactivity of PNHSMA films in coupling reactions with various primary
      amines, including amine-terminated poly(ethylene glycol) (PEG-NH2) and
      fluoresceinamine, was determined by Fourier transform infrared (FTIR)
      spectroscopy, X-ray photoelectron spectroscopy (XPS), fluorescence microscopy,
      and ellipsometry measurements, respectively. The rate constants of PEG-NH2
      attachment on the PNHSMA films were found to be significantly increased compared
      to the coupling on self-assembled monolayers (SAMs) of 11,11'-dithiobis(N
      hydroxysuccinimidylundecanoate) (NHS-C10) on gold under the same conditions. More
      significantly, the PEG loading observed was about 3 times higher for the polymer
      thin films. These data indicate that the coupling reactions are not limited to
      the very surface of the polymer films, but proceed into the near-surface regions
      of the films. PNHSMA films were shown to be stable in contact with aqueous
      buffer; the swelling analysis, as performed by atomic force microscopy (AFM),
      indicated a film thickness independent swelling of approximately 2 nm. An
      increased loading was also observed by surface plasmon resonance for the covalent
      immobilization of amino-functionalized probe DNA. Hybridization of fluorescently
      labeled target DNA was successfully detected by fluorescence microscopy and
      surface plasmon resonance enhanced fluorescence spectroscopy (SPFS), thereby
      demonstrating that thin films of PNHSMA comprise an attractive and simple
      platform for the immobilization of biomolecules with high densities.

PMID- 16283753
TI  - Fibronectin and cell attachment to cell and protein resistant polyelectrolyte
      surfaces.
AB  - Culture of A7r5 smooth muscle cells on a polyelectrolyte multilayer film (PEMU)
      can influence various cell properties, including adhesion, motility, and
      cytoskeletal organization, that are modulated by the extracellular matrix (ECM)
      in vivo. ECM contribution to cell behavior on PEMUs was investigated by
      determining the amount of fibronectin (FN) bound to charged and hydrophobic PEMUs
      by optical waveguide lightmode spectroscopy and immunofluorescence microscopy. FN
      bound best to poly(allylamine hydrochloride) (PAH)-terminated and Nafion
      terminated PEMUs. FN bound poorly to PEMUs terminated with a copolymer of
      poly(acrylic acid) (PAA) and 3-[2-(acrylamido)-ethyl dimethylammonio] propane
      sulfonate (PAA-co-AEDAPS). Cells adhered and spread well on the Nafion-terminated
      PEMU surfaces. In contrast, cells spread less and migrated more on both FN-coated
      and uncoated PAH-terminated PEMU surfaces. Both cells and FN interacted much
      better with Nafion than with PAA-co-PAEDAPS in a micropatterned PEMU. These
      results indicate that A7r5 cell adhesion, spreading, and motility on PEMUs can be
      independent of FN binding to the surfaces.

PMID- 16283754
TI  - Molecular orientation of porphyrins accompanying the formation of chain-aligned
      DNA films.
AB  - Porphyrin-containing DNA solid films with several binding orientations were
      successfully prepared by drying the aqueous solution of porphyrins and DNA in a
      magnetic field. By the measurement of linear dichroism absorption spectra from
      three identical spatial directions, the molecular orientations of porphyrins in
      chain-aligned DNA films were evaluated. Tetra(N-methylpyridinium-4-yl)-porphyrin
      was found to be bound at the surface of DNA chains like a patch. This orientation
      is different from the intercalative or groove binding manners observed in
      solutions. In contrast, tetra(4-sulfonatophenyl)-porphyrin exhibited an
      orientation perpendicular to the DNA axis, which may be attributed to H
      aggregation of porphyrins along the direction parallel to DNA chains. Heme
      protein with coiled coil backbone was also aligned along the DNA chains,
      orienting ferric protoporphyrin parallel to the magnetic field. The major effect
      for these molecular orientations would be the molecular packing of the rod-disk
      or the rod-rod systems.

PMID- 16283755
TI  - Physical gelation of chitosan in the presence of beta-glycerophosphate: the
      effect of temperature.
AB  - When adding beta-glycerophosphate (beta-GP), a weak base, to chitosan aqueous
      solutions, the polymer remains in solution at neutral pH and room temperature,
      while homogeneous gelation of this system can be triggered upon heating. It is
      therefore one of the rare true physical chitosan hydrogels. In this study,
      physicochemical and rheological properties of chitosan solutions in the presence
      of acetic acid and beta-GP were investigated as a function of temperature in
      order to gain a better understanding of the gelation mechanisms. The gel
      structure formed at high temperature was only partially thermoreversible upon
      cooling to 5 degrees C because of the existence of remaining associations,
      confirmed by the spontaneous recovery of the gel after breakup at low
      temperature. Increasing temperature had no effect on the pH values of this
      system, while conductivity (and calculated ionic strength) increased. Values from
      the pH measurements were used to estimate the degree of protonation of each
      species as a function of temperature. The decreasing ratio of -NH3+ in chitosan
      and -OPO(O-)2 in beta-GP suggested reduced chitosan solubility along with a
      diminution of ionic interactions such as ionic bridging with increasing
      temperature. On the other hand, the increased ionic strength as a function of
      temperature, in the presence of beta-GP, enhanced screening of electrostatic
      repulsion and increased hydrophobic effect, resulting in favorable conditions for
      gel formation. Therefore, our study suggests that hydrophobic interactions and
      reduced solubility are the main driving force for chitosan gelation at high
      temperature in the presence of beta-GP.

PMID- 16283756
TI  - Mechanical properties of the sodium montmorillonite interlayer intercalated with
      amino acids.
AB  - Nanosized montmorillonite clay dispersed in small amounts in polymer results in
      polymer nanocomposites having superior engineering properties compared to those
      of the native polymer. These nanoinclusions are created by treating clay with an
      organic modifier which makes clay organophilic and results in intercalation or
      exfoliation of the montmorillonite. The modifiers used are usually long carbon
      chains with alkylammonium or alkylphosphonium cations. In this work, we have
      investigated the use of some alternative molecules which can act as modifiers for
      clay composites using clay for reinforcing a matrix of biopeptides or proteins.
      Such composites have potential applications in the fields of biomedical
      engineering and pharmaceutical science. In this work, the amino acids arginine
      and lysine are used as modifiers. The intercalation and mechanical behavior of
      the interlayer spacing with these amino acids as inclusions under compression and
      tension are studied using molecular dynamics simulations. Significant differences
      in the responses are observed. This work also provides an insight into the
      orientation and interaction of amino acids in the interlayer under different
      stress paths.

PMID- 16283757
TI  - Influence of low-temperature nucleation on the crystallization process of poly(L
      lactide).
AB  - The crystallization kinetics of poly(l-lactide), PLLA, is slow enough to allow a
      quasi-amorphous polymer to be obtained at low temperature simply by quenching
      from the melt. The PLLA crystallization process was followed by differential
      scanning calorimetry and optical microscopy after nucleation isothermal
      treatments at temperatures just below (53 degrees C) and just above (73 degrees
      C) the glass transition temperature. The crystallization exotherm shown in the
      heating thermograms shifts toward lower temperatures as the annealing time at 73
      degrees C increases. The same effect is shown to a lesser extent when the sample
      nucleates at 53 degrees C, showing the ability to nucleate in the glassy state,
      already shown in other polymers. The shape of the DSC thermograms is modeled by
      using Avrami's theory and allows an estimation of the number of crystallization
      germs formed. The results of optical microscopy are converted to thermograms by
      evaluating the average gray level of the image recorded in transmission mode as a
      function of temperature and calculating its temperature derivative. The shape of
      such optical thermograms is quite similar to that of the DSC traces but shows
      some peculiarities after long nucleation treatments. Atomic force microscopy was
      used to analyze the crystal morphology and is an additional proof of the effect
      of nucleation in the glassy state. The crystalline morphology observed in samples
      crystallized after nucleation in the glassy state is qualitatively different from
      that of samples nucleated above the glass transition temperature, and the number
      of crystals seems to be much greater than what could be expected from the
      crystallization kinetics.

PMID- 16283758
TI  - Influence of galactomannans with different molecular weights on the gelation of
      whey proteins at neutral pH.
AB  - The effect of locust bean gum, a galactomannan, with different molecular weights
      on the microstructure and viscoelastic properties of heat-induced whey protein
      gels has been studied using confocal laser scanning microscopy and small
      deformation rheology. The results obtained clearly showed that differences in the
      molecular weight of the polysaccharide have a significant influence on the gel
      microstructure. Homogeneous mixtures and phase-separated systems, with dispersed
      droplet and bicontinuous morphologies, were observed by changing the
      polysaccharide/protein ratio and/or the molecular weight. At 11% whey protein,
      below the gelation threshold of the protein alone, the presence of the nongelling
      polysaccharide induces gelation to occur. At higher protein concentration, the
      main effect of the polysaccharide was a re-enforcement of the gel. However, at
      the higher molecular weight and concentration of the nongelling polymer, the
      protein network starts to lose elastic perfection, probably due to the formation
      of bicontinuous structures with lower connectivity.

PMID- 16283759
TI  - Characterization of a protein-based adhesive elastomer secreted by the Australian
      frog Notaden bennetti.
AB  - When provoked, Notaden bennetti frogs secrete an exudate which rapidly forms a
      tacky elastic solid ("frog glue"). This protein-based material acts as a
      promiscuous pressure-sensitive adhesive that functions even in wet conditions. We
      conducted macroscopic tests in air to assess the tensile strength of moist glue
      (up to 78 +/- 8 kPa) and the shear strength of dry glue (1.7 +/- 0.3 MPa). We
      also performed nanomechanical measurements in water to determine the adhesion
      (1.9-7.2 nN or greater), resilience (43-56%), and elastic modulus (170-1035 kPa)
      of solid glue collected in different ways. Dry glue contains little carbohydrate
      and consists mainly of protein. The protein complement is rich in Gly (15.8 mol
      %), Pro (8.8 mol %), and Glu/Gln (14.1 mol %); it also contains some 4
      hydroxyproline (4.6 mol %) but no 5-hydroxylysine or 3,4-dihydroxyphenylalanine
      (L-Dopa). Denaturing gel electrophoresis of the glue reveals a characteristic
      pattern of proteins spanning 13-400 kDa. The largest protein (Nb-1R, apparent
      molecular mass 350-500 kDa) is also the most abundant, and this protein appears
      to be the key structural component. The solid glue can be dissolved in dilute
      acids; raising the ionic strength causes the glue components to self-assemble
      spontaneously into a solid which resembles the starting material. We describe
      scattering studies on dissolved and solid glue and provide microscopy images of
      glue surfaces and sections, revealing a porous interior that is consistent with
      the high water content (85-90 wt %) of moist glue. In addition to compositional
      similarities with other biological adhesives and well-known elastomeric proteins,
      the circular dichroism spectrum of dissolved glue is almost identical to that for
      soluble elastin and electron and scanning probe microscopy images invite
      comparison with silk fibroins. Covalent cross-linking does not seem to be
      necessary for the glue to set.

PMID- 16283760
TI  - Synthesis and characterization of a pyrrole-alginate conjugate and its
      application in a biosensor construction.
AB  - N-(3-Aminopropyl)pyrrole was covalently coupled with alginate in an aqueous-phase
      reaction by means of carbodiimide-mediated activation chemistry to provide a
      pyrrole-alginate conjugate for subsequent use in biosensor applications. The
      pyrrole-alginate conjugate was quantified by UV spectroscopy at 230 nm, by an
      HPSEC-MALLS analytical method, as well as by FTIR and 13C NMR spectroscopies. The
      new pyrrole-alginate conjugate was used for the immobilization of polyphenol
      oxidase (PPO) onto an electrode surface by physical entrapment resulting from the
      gellification process and electrochemical polymerization of the pyrrole groups.
      The efficiency of this cross-linking approach (chemical and electrochemical) was
      investigated by comparing the amount of enzyme released from polypyrrole-alginate
      and regular alginate. In addition, biosensors were prepared by entrapment of the
      PPO in polypyrrole-alginate and regular alginate matrixes and their performance
      for the amperometric determination of catechol chosen as a model analyte was
      examined, yielding a sensitivity of 350 and 80 microA M(-1) cm(-2), respectively,
      for polypyrrole-alginate and alginate biosensors.

PMID- 16283762
TI  - Thermally induced alpha-helix to beta-sheet transition in regenerated silk fibers
      and films.
AB  - The structure of thin films cast from regenerated solutions of Bombyx mori cocoon
      silk in hexafluoroisopropyl alcohol (HFIP) was studied by synchrotron X-ray
      diffraction during heating. A solid-state conformational transition from an alpha
      helical structure to the well-known beta-sheet silk II structure occurred at a
      temperature of approximately 140 degrees C. The transition appeared to be
      homogeneous, as both phases do not coexist within the resolution of the current
      study. Modulated differential scanning calorimetry (DSC) of the films showed an
      endothermic melting peak followed by an exothermic crystallization peak, both
      occurring near 140 degrees C. Oriented fibers were also produced that displayed
      this helical molecular conformation. Subsequent heating above the structural
      transition temperature produced oriented beta-sheet fibers very similar in
      structure to B. mori cocoon fibers. Heat treatment of silk films at temperatures
      well below their degradation temperature offers a controllable route to materials
      with well-defined structures and mechanical behavior.

PMID- 16283761
TI  - Osteoblast adhesion on poly(L-lactic acid)/polystyrene demixed thin film blends:
      effect of nanotopography, surface chemistry, and wettability.
AB  - Biomaterial surface characteristics are critical cues that regulate cell
      function. We produced a novel series of poly(l-lactic acid) (PLLA) and
      polystyrene demixed nanotopographic films to provide nonbiological cell
      stimulating cues. The increase in PLLA weight fraction (phi) in blend solutions
      resulted in topography changes in spin-cast films from pit-dominant to island
      dominant morphologies having nanoscale depth or height (3-29 nm). Lower molecular
      weight PLLA segregated to the top surface of demixed films, as observed by X-ray
      photoelectron spectroscopy and secondary ion mass spectroscopy (SIMS). For phi >
      or = 0.5, the topmost film layer was predominantly filled with PLLA (>96% by SIMS
      at 20-A depth). Nanotextured substrata stimulated osteoblastic cell adhesion to a
      greater degree than did flat PLLA (phi = 1), and this effect was more pronounced
      for nanoisland (phi = 0.7 and 0.9) relative to nanopit topographies (phi = 0.5).
      Demixed films having relatively lower water contact angles generally enhanced
      cell adhesion and spreading. Our results reveal that cell adhesion is affected by
      surface chemistry, topography, and wettability simultaneously and that
      nanotextured surfaces may be utilized in regulating cell adhesion.

PMID- 16283763
TI  - Calcium-induced changes to the molecular conformation and aggregate structure of
      beta-casein at the air-water interface.
AB  - The influence of calcium on interactions of beta-casein at the air-water
      interface has been studied by several techniques, including interfacial rheology,
      atomic force microscopy (AFM), infrared reflectance-absorbance spectroscopy
      (IRRAS), and zeta potential measurements. In the absence of calcium, a weak
      interfacial gel forms after about 2.5 h. Also in the absence of calcium, the
      adsorbed beta-casein film exhibits some degree of both intra- and intermolecular
      structural organization. For example, IRRAS spectra show a measurable amount of
      alpha-helix content, and AFM images indicate the presence of interfacial
      aggregates with a characteristic lateral length scale of 20-30 nm, which we
      interpret as hemimicelles. Upon the addition of calcium, particularly at Ca:beta
      casein molar ratios above approximately 5:1, a stronger interfacial gel forms
      more quickly; for example, the interfacial shear moduli increase twice as
      rapidly. Also under these conditions (5:1 Ca:beta-casein ratio) there is little
      evidence of structural organization; i.e., the alpha-helix peaks are very weak,
      and AFM images show a disordered, but continuous film, without distinct
      hemimicelles. On the basis of these findings, we hypothesize that calcium binding
      destabilizes the coupled intra- and intermolecular structural organization, and
      that the loss of organization permits more rapid interfacial gelation. These
      phenomena are characteristic of the air-water interface; they are not accompanied
      by analogous structural changes in bulk solution.

PMID- 16283764
TI  - Structural characterization of self-assembled polypeptide films on titanium and
      glass surfaces by atomic force microscopy.
AB  - Chemically modified biomaterial surfaces (titanium and glass) covered with
      polyelectrolyte self-assembled films formed by the alternating adsorption of
      cationic poly-L-lysine (PLL) and anionic poly-L-glutamic acid (PGA) were
      structurally characterized by atomic force microscopy. Complementary information
      concerning the thickness and layer-by-layer growth of the films was provided by
      optical waveguide light-mode spectroscopy. The frequently used ex situ and the
      rarely used in situ build-up methods were compared. Important aspects of the
      industrial applicability of these films, their stability in time, and possible
      differences in their morphology were investigated. The films revealed a granular
      pattern, with grain diameters of 270 +/- 87 nm for glass (up to 8 bilayers) and
      303 +/- 89 nm for titanium (up to 10 bilayers), independently of the build-up
      procedure. Both surfaces displayed a rehydration capability, the titanium surface
      exhibiting a better stability in time. The high roughness values observed at
      acidic or basic pH are related to the degree of ionization of PGA and PLL.

PMID- 16283765
TI  - Novel functional biodegradable polymer IV: pH-sensitive controlled release of
      fibroblast growth factor-2 from a poly(gamma-glutamic acid)-sulfonate matrix for
      tissue engineering.
AB  - The acidic pH-sensitive controlled release of fibroblast growth factor-2 (FGF-2)
      from a biodegradable hydrogel without any denaturation of the FGF-2 was
      successfully performed by a combination of FGF-2 activity and acidic pH
      sensitivity. We prepared semi-interpenetrating polymer network like hetero-gels
      (S72-netgels) composed of poly(gamma-glutamic acid) (gamma-PGA) and 72%
      sulfonated gamma-PGA (gamma-PGA-S72). S72-netgels including 36 mol % sulfonic
      acid (S72-netgel-36) showed wide acidic pH-sensitive deswelling properties at pH
      = 2.0-6.0, corresponding to the isoelectric point of carboxylic acid, because of
      the concentration of protons due to the neighboring sulfonic acids from the
      carboxylic acids. The S72-netgel-36 (the volume of hydrogel is 7.85 x 10(-2) cm3)
      can incorporate 280 ng of FGF-2 after 24 h immersion in Tris-HCl buffer (pH =
      7.4), including 1.0 microg of FGF-2. The S72-netgel-36 still retained about 60%
      of the FGF-2 even after 15 days of incubation in fresh Tris-HCl buffer at 37
      degrees C because of the stable interaction of FGF-2 with gamma-PGA-S72 in S72
      netgel-36. The release of FGF-2 from the S72-netgel-36 was successfully
      controlled by alternating immersion in pH = 7.4 and acidic pH buffers.
      Furthermore, the FGF-2 released from the S72-netgel-36 retained its activity
      without denaturation because the gamma-PGA-S72 in S72-netgel-36 has a protective
      activity. The acidic pH-sensitive FGF-2 release property of the S72-netgel-36
      without denaturation of the FGF-2 may be useful for tissue engineering fields
      such as neovascular treatment for ischemia and inflammation.

PMID- 16283766
TI  - Influence of chitosan structure on the formation and stability of DNA-chitosan
      polyelectrolyte complexes.
AB  - The interactions between DNA and chitosans varying in fractional content of
      acetylated units (FA), degree of polymerization (DP), and degree of ionization
      were investigated by several techniques, including an ethidium bromide (EtBr)
      fluorescence assay, gel retardation, atomic force microscopy, and dynamic and
      electrophoretic light scattering. The charge density of the chitosan and the
      number of charges per chain were found to be the dominating factors for the
      structure and stability of DNA-chitosan complexes. All high molecular weight
      chitosans condensed DNA into physically stable polyplexes; however, the
      properties of the complexes were strongly dependent on FA, and thereby the charge
      density of chitosan. By employing fully charged oligomers of constant charge
      density, it was shown that the complexation of DNA and stability of the
      polyplexes is governed by the number of cationic residues per chain. A minimum of
      6-9 positive charges appeared necessary to provide interaction strength
      comparable to that of polycations. In contrast, further increase in the number of
      charges above 9 did not increase the apparent binding affinity as judged from the
      EtBr displacement assay. The chitosan oligomers exhibited a pH-dependent
      interaction with DNA, reflecting the number of ionized amino groups. The
      complexation of DNA and the stability of oligomer-based polyplexes became reduced
      above pH 7.4. Such pH-dependent dissociation of polyplexes around the
      physiological pH is highly relevant in gene delivery applications and might be
      one of the reasons for the high transfection activity of oligomer-based
      polyplexes observed.

PMID- 16283767
TI  - Imaging of high-amylose starch tablets. 3. Initial diffusion and temperature
      effects.
AB  - The penetration of water into cross-linked high amylose starch tablets was
      studied at different temperatures by nuclear magnetic resonance (NMR) imaging,
      which follows the changes occurring at the surface and inside the starch tablets
      during swelling. It was found that the swelling was anisotropic, whereas water
      diffusion was almost isotropic. The water proton image profiles at the initial
      stage of water penetration were used to calculate the initial diffusion
      coefficient. The swelling and water concentration gradients in this controlled
      release system show significant temperature dependence. Diffusion behavior
      changed from Fickian to Case II diffusion with increasing temperature. The
      observed phenomena are attributed to the gelatinization of starch and the pseudo
      cross-linking effect of double helix formation.

PMID- 16283768
TI  - Molecular weight effect on liquid crystalline gel formation of curdlan.
AB  - Curdlan dissolved in alkaline solution forms a unique gel consisting of liquid
      crystalline gel (LCG) and amorphous gel (AG) in alternating layers by a dialysis
      into aqueous calcium chloride. The unique structure has been investigated by
      measuring the birefringence of the gel Deltan, the ratio q of the thickness of
      LCG layer delta to the gel radius R, and the calcium content in the gel C(Ca) in
      a wide range of molecular weights of fractionated Curdlan, as well as
      unfractionated Curdlan as a control. With increasing molecular weight of Curdlan,
      Deltan increased and q = delta/R decreased, and both became saturated at high
      molecular weight. Deltan and q for unfractionated Curdlan were smaller and
      larger, respectively, than those for fractionated Curdlan. C(Ca) was constant
      irrespective of molecular weight and its distribution, which means that the
      abundance of calcium ions per glucose unit in the gel does not depend on the
      degree of orientation of mesogens. These results suggest that the amorphous phase
      appears when the size of the Curdlan molecules is larger than the average
      intermolecular distance, resulting from the random coil to triple helix
      transformation of Curdlan molecules associated with lowering hydroxide anion
      concentration in the dialysis process.

PMID- 16283769
TI  - Synthesis of uniform protein-polymer conjugates.
AB  - We have developed a novel technique to synthesize near-uniform protein-polymer
      conjugates by initiating atom transfer radical polymerization of monomethoxy
      poly(ethylene glycol)-methacrylate from 2-bromoisobutyramide derivatives of
      chymotrypsin (a protein-initiator). Polymerization initiated from the
      monosubstituted protein-initiator resulted in the conjugate containing a single,
      near-monodisperse polymer chain per protein molecule with polydispersity index
      1.05. Increasing the number of conjugated 2-bromoisobutyramide initiators per
      molecule of protein increased the molecular weights and polydispersity indices of
      the final protein-polymer conjugates. The generic nature of this technique was
      demonstrated by initiating polymerization of nonionic, cationic, and anionic
      monomers from the protein-initiator. Protein-polymer conjugates synthesized by
      this novel technique retained 50-86% of the original enzyme activity. The
      technique described herein should be useful in synthesizing well-defined protein
      polymer conjugates exhibiting a wide range of physical and chemical properties.

PMID- 16283770
TI  - Pretreatment of amphiphilic comb polymer surfaces dramatically affects protein
      adsorption.
AB  - New applications in regenerative biotechnology require the ability to understand
      and control protein-surface interactions on micrometer and submicrometer length
      scales. Evidence presented here shows that micropatterned amphiphilic comb
      polymer films exhibit a pretreatment-dependent behavior with respect to protein
      adsorption for the proteins fibronectin, laminin, and for serum. A micropatterned
      surface, consisting of protein-reactive regions, separated by comb polymer, was
      created and tested for protein adsorption using the surface-sensitive imaging
      tool TOF-SIMS. Immersion of micropatterned surfaces in solutions of fibronectin
      or laminin resulted in uniform protein coverage on both the comb polymer and
      protein-reactive regions. However, preimmersion of similarly patterned surfaces
      in water for 2 h prior to protein incubation was found to dramatically improve
      the protein-resistant properties of the comb polymer regions. These results are
      consistent with poly(ethylene glycol) (PEG) side chain reorientation and/or
      hydration and poly(methyl methacrylate) (PMMA) backbone segregation away from the
      interface region.

PMID- 16283771
TI  - Albumin clusters: structurally defined protein tetramer and oxygen carrier
      including thirty-two iron(II) porphyrins.
AB  - Recombinant human serum albumin (rHSA) clusters have been synthesized and
      physicochemically characterized. Cross-linking between the Lys groups of the core
      albumin and a unique Cys-34 of the shell albumins with an N-succinimidyl-6-[3'-(2
      pyridyldithio)propionamido]hexanoate produced the structurally defined rHSA
      trimer and tetramer. MALDI-TOF-MS showed a single peak with the triple and
      quadruple masses of rHSA. Their molar ellipticities and the isoelectric points
      (pI = 4.8) are all identical to those of the monomer, suggesting that the
      essential structures of the albumin units were intact. TEM observations
      demonstrated a uniform morphology of the rHSA tetramer with a diameter of 20-30
      nm. The circulation half-life (tau1/2) of the 125I-labeled rHSA tetramer in rat
      (5.5 h) was significantly longer than that of the monomer (2.3 h) due to the low
      ratio of the distribution phase (alpha-phase). A total of 24 and 32 molecules of
      the synthetic iron(II) porphyrins (FePs) are incorporated into the hydrophobic
      cavities of the rHSA trimer and tetramer, respectively, producing huge artificial
      hemoproteins. These albumin-heme clusters can reversibly bind and release O2
      under physiological conditions (37 degrees C, pH 7.3) and showed similar O2
      binding properties (O2-binding affinity, association and dissociation rate
      constants) to those of the corresponding monomer. A large volume of O2 can be
      chemically dissolved into the albumin-heme cluster solutions relative to the
      monomeric rHSA-FeP when the molar concentration of the albumin scaffold is
      identical.

PMID- 16283772
TI  - Enzymatic surface erosion of poly(trimethylene carbonate) films studied by atomic
      force microscopy.
AB  - In this article, the surface erosion of spin-coated poly(trimethylene carbonate)
      (PTMC) films by lipase solutions from Thermomyces lanuginosus was studied using
      atomic force microscopy (AFM). PTMC films (23-48 nm thick) were stable in water
      at 37 degrees C for 16 h, while after immersion in lipase solutions at 37 degrees
      C for 30 s and 1 min, the average thickness of the film decreased in time at a
      rate of 11.0 +/- 3.7 nm/min. The initially smooth films became significantly
      rougher during the erosion process. When the immersion time of the films in the
      lipase solutions was limited to less than 5 s, degradation of the surface was
      minimal and individual lipase molecules adsorbed on PTMC films could be
      discerned. By microcontact printing of the PTMC surfaces using a patterned PDMS
      stamp and lipase solution for 30 s, a predefined micropattern consisting of
      parallel, 5-microm-wide lines lying 5-nm deep and separated at a distance of 2
      microm was formed. Friction images showed differences in surface properties
      between the recessed and protruding lines in the pattern.

PMID- 16283773
TI  - Evaluation of acrylate-based block copolymers prepared by atom transfer radical
      polymerization as matrices for paclitaxel delivery from coronary stents.
AB  - Acrylate-based block copolymers, synthesized by atom transfer radical
      polymerization (ATRP) processes, were evaluated as drug delivery matrices for the
      controlled release of paclitaxel from coronary stents. The polymers were
      multiblock copolymers consisting of poly(butyl acrylate) or poly(lauryl acrylate)
      soft blocks and hard blocks composed of poly(methyl methacrylate), poly(isobornyl
      acrylate), or poly(styrene) homo- or copolymers. Depending on the ratio of hard
      to soft blocks in the copolymers, coating formulations were produced that
      possessed variable elastomeric properties, resulting in stent coatings that
      maintained their integrity when assessed by scanning electron microscopy (SEM)
      imaging of overexpanded stents. In vitro paclitaxel release kinetics from
      coronary stents coated with these copolymers typically showed an early burst
      followed by sustained release behavior, which permitted the elution of the
      majority of the paclitaxel over a 10-day time period. It was determined that
      neither the nature of the polyacrylate (n-butyl or lauryl) nor that of the hard
      block appeared to affect the release kinetics of paclitaxel at a loading of 25%
      drug by weight, whereas some effects were observed at lower drug loading levels.
      Differential scanning calorimetry (DSC) analysis indicated that the paclitaxel
      was at least partially miscible with the poly(n-butyl acrylate) phase of those
      block copolymers. The copolymers were also evaluated for sterilization stability
      by exposing both the copolymer alone and copolymer/paclitaxel coated stents to e
      beam radiation at doses of 1-3 times the nominal dose used for medical device
      sterilization (25 kGy). It was found that the copolymers containing blocks
      bearing quaternary carbons within the polymer backbone were less stable to the
      radiation and showed a decrease in molecular weight as determined by gel
      permeation chromatography. Conversely, those without quaternary carbons showed no
      significant change in molecular weight when exposed to 3 times the standard
      radiation dose. There was no significant change in drug release profile from any
      of the acrylate-based copolymers after exposure to 75 kGy of e-beam radiation,
      and this was attributed to the inherent radiation stability of the poly(n-butyl
      acrylate) center block.

PMID- 16283774
TI  - Hemagglutinin linear epitope presentation on monolayer-protected clusters elicits
      strong antibody binding.
AB  - Immunoreactive, multicomponent nanoclusters were assembled through the controlled
      presentation of a known, synthetic peptide epitope. The epitope comes from the
      hemagglutanin protein of influenza and is known to bind to a monoclonal anti-HA
      antibody. Antibody affinity for the immunoreactive MPC was compared to the
      affinity for traditionally used peptide arrays using the quartz crystal
      microbalance. The two systems had comparable affinities (Ka), ranging from 0.41 x
      10(7) M(-1) to 1.8 x 10(7) M(-1), though the nanocluster used a much lower
      density of peptide relative to that of the peptide array. These results suggest
      that functionalized nanoclusters have potential in nanostructure assembly and
      medical applications. Water-soluble nanoparticles that present known neutralizing
      peptide epitopes of protein antigens might be used in antiviral influenza
      vaccines.

PMID- 16283776
TI  - From ultrathin capsules to biaqueous vesicles.
AB  - The layer-by-layer (LbL) adsorption of anionic polyelectrolytes (PE) and
      tobramycin sulfate (TbS) multilayers on zinc oxide core particles followed by the
      controlled core-removal process leads to the formation of ultrathin capsules,
      which gradually convert to biaqueous vesicles and emulsionlike systems depending
      on the hydrophilicity/hydrophobicity of the PE backbone, PE/TbS ratio, and Zn2+
      concentration. The unique characteristics of the PE/TbS multilayer capsules
      result because of the formation of PE/TbS/H2O biphasic liquid systems unlike the
      other LbL capsular systems that form stiff PE coacervates when mixed together in
      water. This paper investigates the PE/TbS ultrathin capsule to biaqueous vesicle
      transition and its physicochemical properties.

PMID- 16283775
TI  - Fate of prions in soil: adsorption kinetics of recombinant unglycosylated ovine
      prion protein onto mica in laminar flow conditions and subsequent desorption.
AB  - Prions can be disseminated in soils. Their interaction with soil minerals is a
      key factor for the assessment of risks associated with the transport of their
      infectivity. We did not examine here the infectivity itself but the adsorption
      kinetics of an ovine recombinant prion protein (ovine PrPrec), as a noninfectious
      model protein, on muscovite mica, a phyllosilicate with surface properties
      analogous to soil clays, in conditions of laminar flow through a channel. The
      protein was labeled with (125)I, and its adsorption examined between pH 4.0 and
      9.0. At wall shear rate 100 s(-1), we found the process to be controlled mainly
      by transport at the beginning of the adsorption process. Additional experiments
      at 1000 s(-1) (pH 5 and 6) determined that the diffusion coefficient was in
      accordance with the hydrodynamic radius measured by size exclusion
      chromatography. The pseudo-plateau of the interfacial concentration with time was
      compatible with more than a monolayer and suggests the presence of aggregates.
      Desorption was not observed in the presence of buffer between pH 4 and 9 and
      sheep plasma, while the addition of alkaline detergent or 10(-1) M NaOH allowed
      an almost complete removal from the interface. The ensemble of results suggests
      that the largely irreversible adsorption of the ovine PrPrec onto mica is mainly
      due to electrostatic attraction between the protein and the highly negatively
      charged mica surface. Possible consequences for the mode of dissemination of
      prion proteins in soils are indicated.

PMID- 16283777
TI  - Low molecular weight linear polyethylenimine-b-poly(ethylene glycol)-b
      polyethylenimine triblock copolymers: synthesis, characterization, and in vitro
      gene transfer properties.
AB  - Novel ABA triblock copolymers consisting of low molecular weight linear
      polyethylenimine (PEI) as the A block and poly(ethylene glycol) (PEG) as the B
      block were prepared and evaluated as polymeric transfectant. The cationic
      polymerization of 2-methyl-2-oxazoline (MeOZO) using PEG-bis(tosylate) as a
      macroinitiator followed by acid hydrolysis afforded linear PEI-PEG-PEI triblock
      copolymers with controlled compositions. Two copolymers, PEI-PEG-PEI 2100-3400
      2100 and 4000-3400-4000, were synthesized. Both copolymers were shown to interact
      with and condense plasmid DNA effectively to give polymer/DNA complexes
      (polyplexes) of small sizes (<100 nm) and moderate zeta-potentials (approximately
      +10 mV) at polymer/plasmid weight ratios > or =1.5/1. These polyplexes were able
      to efficiently transfect COS-7 cells and primary bovine endothelial cells (BAECs)
      in vitro. For example, PEI-PEG-PEI 4000-3400-4000 based polyplexes showed a
      transfection efficiency comparable to polyplexes of branched PEI 25000. The
      transfection activity of polyplexes of PEI-PEG-PEI 4000-3400-4000 in BAECs using
      luciferase as a reporter gene was 3-fold higher than that for linear PEI
      25000/DNA formulations. Importantly, the presence of serum in the transfection
      medium had no inhibitive effect on the transfection activity of the PEI-PEG-PEI
      polyplexes. These PEI-PEG-PEI triblock copolymers displayed also an improved
      safety profile in comparison with high molecular weight PEIs, since the
      cytotoxicity of the polyplex formulations was very low under conditions where
      high transgene expression was found. Therefore, linear PEI-PEG-PEI triblock
      copolymers are an attractive novel class of nonviral gene delivery systems.

PMID- 16283778
TI  - Synthesis, characterization, and degradation behavior of amphiphilic poly
      alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide]-g-poly(epsilon-caprolactone).
AB  - A series of biodegradable amphiphilic graft polymers were successfully
      synthesized by grafting poly(epsilon-caprolactone) (PCL) sequences onto a water
      soluble poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA) backbone. The
      graft copolymers were prepared through the ring-opening polymerization of epsilon
      caprolactone (CL) initiated by the macroinitiator PHEA with pendant hydroxyl
      groups without adding any catalyst. By controlling the feed ratio of the
      macroinitiator to the monomer, the copolymers with different branch lengths and
      properties can be obtained. The successful grafting of PCL sequences onto the
      PHEA backbone was verified by FTIR, 1H NMR, and combined size-exclusion
      chromatography and multiangle laser light scattering (SEC-MALLS) analysis. The
      hydrolytic degradation and enzymatic degradation of these graft copolymers were
      investigated. The results show the hydrolytic degradation rate increases with
      increasing content of hydrophilic PHEA backbone. While the enzymatic degradation
      rate is affected by two competitive factors, the catalytic effect of Pseudomonas
      cepacia lipase on the degradation of PCL branches and the hydrophilicity which
      depends on the copolymer composition. In situ observation of the degradation
      under polarizing light microscope (PLM) demonstrates the different degradation
      rates of different regions in the polymer samples.

PMID- 16283779
TI  - Atomic force microscopy reveals aggregation of gastric mucin at low pH.
AB  - Mammalian gastric mucin, at high concentration, is known to form a gel at low pH,
      behavior essential to the protection of the stomach from auto-digestion. Atomic
      force microscopy (AFM) measurements of dilute solutions of porcine gastric mucin
      in an aqueous environment in the pH range 6-2 provide a direct visualization of
      extended fiberlike molecules at pH 6 that aggregate at pH 4 and below forming
      well-defined clusters at pH 2. The clusters consist of 10 or less molecules. AFM
      images of mucin at high concentration at pH 2 reveal clusters similar to those
      seen in the dilute solutions at low pH. We also imaged human gastric mucus
      revealing a network having a "pearl necklace" structure. The "pearls" are similar
      in size to the clusters found in the purified porcine gastric mucin gels. AFM
      images of deglycosylated mucin reveal that the deglycosylated portions of the
      molecule re-fold into compact, globular structures suggesting that the
      oligosaccharide chains are important in maintaining the extended conformation of
      mucin. However, the oligosaccharides do not appear to be directly involved in the
      aggregation at low pH, as clusters of similar size are observed at pH 2 in both
      native and deglycosylated mucin.

PMID- 16283780
TI  - Structural differences between the lignin-carbohydrate complexes present in wood
      and in chemical pulps.
AB  - Lignin-carbohydrate complexes (LCCs) were prepared in quantitative yield from
      spruce wood and from the corresponding kraft and oxygen-delignified pulps and
      were separated into different fractions on the basis of their carbohydrate
      composition. To obtain an understanding of the differences in lignin structure
      and reactivity within the various LCC fractions, thioacidolysis in combination
      with gas chromatography was used to quantify the content of beta-O-4 structures
      in the lignin. Periodate oxidation followed by determination of methanol was used
      to quantify the phenolic hydroxyl groups. Furthermore, size exclusion
      chromatography (SEC) of the thioacidolysis fractions was used to monitor any
      differences between the original molecular size distribution and that after the
      delignification processes. Characteristic differences between the various LCC
      fractions were observed, clearly indicating that two different forms of lignin
      are present in the wood fiber wall. These forms are linked to glucomannan and
      xylan, respectively. On pulping, the different LCCs have different reactivities.
      The xylan-linked lignin is to a large extent degraded, whereas the glucomannan
      linked lignin undergoes a partial condensation to form more high molecular mass
      material. The latter seems to be rather unchanged during a subsequent oxygen
      delignification stage. On the basis of these findings, a modified arrangement of
      the fiber wall polymers is suggested.

PMID- 16283781
TI  - New facile approach to novel water-soluble aliphatic poly(butylene tartarate)s
      bearing reactive hydroxyl pendant groups.

PMID- 16283784
TI  - Comprehensive survey of combinatorial library synthesis: 2004.

PMID- 16283782
TI  - DNA condensation induced by nanoparticle-embedded dendrimer leading to pearl
      chain nanowires.

PMID- 16283785
TI  - Syntheses of 5-Oxa-10,11-diazadibenzo[a,d]cycloheptenes on solid supports.

PMID- 16283786
TI  - Lewis acid catalyzed solid-phase synthesis of flavonoids using selenium-bound
      resin.

PMID- 16283787
TI  - Synthesis of 4-Oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-6-carboxamides using
      a modification of Ugi condensation.

PMID- 16283788
TI  - Solid-phase synthesis of 1,2,3-trisubstituted indoles and 2,3-disubstituted
      benzofurans via iodocyclization.

PMID- 16283789
TI  - Novel heterocyclic scaffold consisting of indole-fused pteridines.

PMID- 16283790
TI  - Solid-phase synthesis of 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives via
      selective, reagent-based cyclization of acyldithiocarbazate resins.

PMID- 16283791
TI  - Parallel synthesis and rapid photochemical screening of organosoluble Ru(II)
      photosensitizers.
AB  - Ru(II) complexes of heteroaromatic ligands are photosensitizers of interest in
      such applications as photovoltaic cells. Their bulk preparation is tedious, time
      consuming, and expensive. Their assessments, by measurement of the individual
      excited-state lifetimes, is incomplete and requires specialized equipment and
      expertise, as well as time. The identification of new, promising photosensitizers
      would, therefore, greatly benefit from any time- and cost-saving protocol, if
      absolute purity is not required for assessment. This paper details a protocol for
      the fairly rapid preparation, in parallel and on a small scale, of organosoluble
      Ru(II) complexes in a state ready for screening for photosensitization ability.
      The protocol was tested with a small set of bidentate ligands, generating 20
      possible complexes, many of which are known. The protocol was found to produce
      predominantly the desired species in all cases except those with three different
      ligands. The batch screening results for the remaining 16 complexes were entirely
      consistent with those obtained with pure samples of the most promising materials
      prepared in bulk and were consistent with known photophysical properties.

PMID- 16283792
TI  - Syntheses of 1,3-Imidazoline-2-thione and 2-Phenylimino-1,3-thiazoline
      combinatorial libraries through different sequences of the same components.
AB  - We have developed combinatorial libraries of new 1,3-imidazoline-2-thiones 5 and
      2-phenylimino-1,3-thiazolines 7 by way of different reaction sequences of the
      same three components, gamma-chloroacetoacetanilides 1, amines 2, and
      isothiocyanates 3 in a parallel synthetic fashion. One of the building blocks,
      the gamma-chloroacetoacetanilides 1, was prepared by the sequential reaction of 4
      methylene-oxetan-2-one (ketene dimer) with chlorine and various anilines. The
      condensation of 1 with amines gave dihydrofuran 4 intermediates that when reacted
      with 3 afforded the 1,3-imidazoline-2-thiones 5. On the other hand, reaction of 3
      with 2 provided substituted thioureas 6 that were reacted with 1 to yield 2
      phenylimino-1,3-thiazolines 7.

PMID- 16283793
TI  - Natural products as scaffolds for chemical diversification: solution-phase
      parallel synthesis of a series of naringin analogues.
AB  - The flavanone glycoside naringin hydrate is widely abundant in various citrus
      plants. As an ongoing effort toward the exploitation of natural products as
      scaffolds for chemical diversification at readily accessible positions, we have
      prepared a series of analogues of naringin in which the 6-hydroxyl group of the
      beta-d-glucopyranosyl subunit was converted to sulfonamides, amides, urethanes,
      and secondary and tertiary amines via the corresponding 6-amino derivative using
      a solution-phase parallel array protocol.

PMID- 16283794
TI  - Evaluation of solution and solid-phase approaches to the synthesis of libraries
      of alpha,alpha-disubstituted-alpha-acylaminoketones.
AB  - Solid phase, solution, and hybrid approaches to the synthesis of small focused
      libraries of alpha,alpha-disubstituted-alpha-acylaminoketones have been explored.
      Solution and hybrid approaches that used support-bound reagents and scavenger
      resins were the most productive.

PMID- 16283795
TI  - Aza-amino acid scanning of secondary structure suited for solid-phase peptide
      synthesis with fmoc chemistry and aza-amino acids with heteroatomic side chains.
AB  - Aza-peptides, peptide analogues in which the alpha-carbon of one or more of the
      amino acid residues is replaced with a nitrogen atom, exhibit a propensity for
      adopting beta-turn conformations. A general Fmoc-protection protocol for the
      stepwise solid-phase synthesis of aza-peptides has now been developed based on
      the activation of N'-alkyl fluoren-9-ylmethyl carbazates with phosgene for
      coupling the aza-amino acid residues. This method has proven effective for
      introducing aza-amino acid residues with aliphatic (Ala, Leu, Val, and Gly) and
      aromatic (Phe, Tyr, and Trp) side chains. Acid promoted loss of aromatic side
      chains was noted with aza-Trp and aza-Tyr residues during peptide cleavage and
      suppressed by temperature control in the case of the latter. In addition, aza
      peptides with heteroatomic side chain residues (Lys, Orn, Arg, and Asp) were
      conveniently synthesized using this protocol. Partial aza-amino acid scans were
      performed on three biologically active peptides: the potent tetrapeptide
      melanocortin receptor agonist, Ac-His-d-Phe-Arg-Trp-NH2; the growth hormone
      secretagogue hexapeptide, GHRP-6, His-d-Trp-Ala-Trp-d-Phe-Lys-NH2; and the human
      calcitonin gene-related peptide (hCGRP) antagonist, FVPTDVGPFAF-NH2. This
      practical procedure for aza-amino acid scanning using Fmoc-based solid-phase
      synthesis should find general utility for probing the existence and importance of
      beta-turn conformations in bioactive peptides.

PMID- 16283796
TI  - Solid phase synthesis of pyridine-based derivatives from a 2-chloro-5
      bromopyridine scaffold.
AB  - 2-Chloro-5-bromopyridine was immobilized on polystyrene via selective
      introduction of a traceless silicon linker at the C-4 position. A useful scaffold
      was thus obtained, as demonstrated by efficient and selective reactions with
      polar and transition organometallic reagents, opening a new access to pyridine
      based libraries of synthons and chromophores.

PMID- 16283797
TI  - Photochemical generation of nitrosocarbonyl intermediates on solid phase:
      synthons toward hetero Diels-Alder and Ene adducts through photocleavage.
AB  - The synthesis of 1,2,4-oxadiazole-4-oxides on polystyrenic solid phase docked at
      the position 3 of the heterocyclic ring has been performed through the
      cycloaddition of stable supported nitrile oxides to amidoximes. The photochemical
      cycloreversion of these heterocycles afforded the free nitrosocarbonyl
      intermediates that were trapped by suitable dienes or enes. The method is
      proposed as a clean and environmental friendly approach to the fleeting
      nitrosocarbonyl intermediates, which afford valuable adducts for various
      synthetic applications. The isomeric heterocycles docked at the position 5 of the
      ring have also been obtained by cycloaddition of nitrile oxides to supported
      amidoximes. Their photolysis afforded resin-bound nitrosocarbonyls that were
      trapped with dienes affording valuable supported adducts suitable for further
      elaboration on solid-phase chemistry.

PMID- 16283798
TI  - Plate-to-plate fluorous solid-phase extraction for solution-phase parallel
      synthesis.
AB  - A commercially available Argonaut VacMaster-96 plate-to-plate solid-phase
      extraction (SPE) station equipped with 24 FluoroFlash cartridges is employed for
      parallel purification of fluorous reaction mixtures. Each cartridge charged with
      3 g of fluorous silica gel has the capability to produce up to 100 mg of purified
      small molecules. The 24-well receiving plate has a standard footprint that can be
      directly concentrated in a Genevac vacuum centrifuge. Important issues such as
      sample loading, product cross-contamination, cartridge reuse, and reproducibility
      are investigated. The SPE system has been demonstrated in the purification of
      three small libraries that were produced involving amine scavenging reactions
      with fluorous isatoic anhydride, amide coupling reactions with 2-chloro-4,6
      bis[(perfluorohexyl)propyloxy]-1,3,5-triazine (fluorous CDMT), and amide coupling
      reactions with a newly developed fluorous Mukaiyama condensation reagent.

PMID- 16283799
TI  - Tethered dimer inhibitors of NAD synthetase: parallel synthesis of an aryl
      substituted SAR library.
AB  - We previously reported that tethered dimers containing indoles on one end and a
      permanent positive charge on the other, using a 6-9 carbon polymethylene tether,
      provided NAD synthetase inhibitors with impressive antibacterial activities
      against Gram-positives. Here, we report that the phenyl ring is a good substitute
      for indole, and we utilize solution-phase parallel synthesis to explore structure
      activity relationships for substituents on that ring. General conclusions are
      that nonpolar substituents are more effective than polar ones and that different
      positional isomers often have very different enzyme inhibition activities. This
      latter observation reveals that enzyme activity is sensitive to minor structural
      changes and suggests that nonspecific detergent actions are not important for the
      observed effects.

PMID- 16283800
TI  - Synthesis of 1-alkyl-4-imidazolecarboxylates: a catch and release strategy.
AB  - The novel alkyl N-methyl-N-polystyreneamino-2-isocyanoacrylate was used for the
      synthesis of 1-substituted imidazole-4-carboxylates utilizing a "catch and
      release" methodology. The reactions were performed under microwave irradiation,
      affording the title compounds in both high yields and chemical purity directly to
      solution, from the solid phase support.

PMID- 16283801
TI  - Solid-phase synthesis of 2-aminoquinazolinone derivatives with two- and three
      point diversity.
AB  - A versatile solid-phase method for the synthesis of various substituted 2-amino
      4(3H)-quinazolinones with two- and three-point diversity is described. The
      synthesis commenced with the generation of polymer-bound S-methylisothiourea
      followed by N-acylation with different substituted o-nitrobenzoic acid. Finally,
      reduction of the nitro group triggered intramolecular cyclization via formation
      of guanidine to afford 2-amino-4(3H)-quinazolinone and its derivatives in high
      yields and purities.

PMID- 16283802
TI  - A highly efficient solid-phase synthesis of 1,3-substituted xanthines.
AB  - A first solid-phase route to 1,3-substituted xanthines has been developed using
      PS-MB-CHO resin. Cyclocondensation of the polymer-bound aminoimidazole with
      isocyanates followed by alkylation provided 1,3-substituted xanthines in high
      yields. Libraries of 12 xanthines and 4 thioxanthines were prepared.

PMID- 16283803
TI  - Parallel synthesis and high throughput dissolution testing of biodegradable
      polyanhydride copolymers.
AB  - We have demonstrated that polycondensation reactions can be carried out in a
      combinatorial fashion and that the polymer library can be screened at high
      throughput using a rapid prototyping technique to fabricate multiwell substrates.
      A linearly varying compositional library of 100 different biodegradable
      polyanhydride random copolymers that are promising carriers for controlled drug
      delivery was designed, fabricated, and characterized by IR microscopy within a
      few hours. The polyanhydride copolymer library was based on 1,6-bis(p
      carboxyphenoxy)hexane (CPH) and sebacic anhydride (SA) and was characterized with
      infrared microspectroscopy to determine the composition within each well. Since
      degradation and release rates depend on copolymer composition, we also developed
      new high-throughput methods to investigate drug release from this library of
      copolymers by designing specific wells for each task. A subset of this library
      was chosen, and a substrate was designed and fabricated to enable the synthesis
      and monitoring of dye dissolution from a range of polyanhydride copolymers in a
      parallel fashion using a CCD camera. Multisample substrates were fabricated with
      a novel rapid prototyping method that consists of an organic solvent-resistant
      array of 10 x 10 microwells of 2-muL volume each. The libraries were deposited
      with a custom-built liquid dispensing system consisting of a series of computer
      controlled volume-dispensing pumps and XYZ motion stages. The parallel dye
      dissolution study displayed a decreasing rate of release with increasing CPH
      content. This result agrees with previously published data for dye release from
      poly(CPH-co-SA) copolymers. The methodology described in this work is amenable to
      numerous applications in the arenas of high-throughput polymer synthesis and
      characterization.

PMID- 16283804
TI  - Understanding supported reactions in spherical compartments: a general algorithm
      to model and determine rate constants, diffusion coefficients, and spatial
      product distributions.
AB  - A general algorithm allowing the numerical modeling of the time and space
      dependence of product formation in spherical reaction volumes is described. The
      algorithm is described by the complete set of mass balance equations. On the
      basis of these equations, the effects of the diffusion coefficient, reaction
      rate, bead size, reagent excess, and packing density of the resin beads on the
      overall reaction rates are determined for second-order reactions. Experimental
      data of reaction progress are employed to calculate reaction rates and diffusion
      coefficients in polymer-supported reactions. In addition, the conditions for
      shell-like product formation are determined, and various strategies for the
      radial patterning of resin beads are compared. The effect of diffusion on polymer
      supported enzyme-catalyzed reactions of the Michaelis-Menten type is treated, as
      well. Finally, the effects of typical nonideal solid-phase phenomena, namely, the
      inhomogeneity of rate constants and the concentration dependence of diffusion
      coefficients, on overall rates are discussed.

PMID- 16283805
TI  - Parallel solution combustion synthesis for combinatorial materials studies.
AB  - A parallel solution combustion synthesis technique was developed for
      combinatorial materials studies. The vigorous combustion reactions were
      successfully limited in the microreactors by using a substrate-net-mask
      microreactor system and the lowest adoptable furnace temperature. Using this
      technique, a luminescent materials library of Y3Al5O12/Tb(chi) was synthesized
      with the aid of an ink-jet delivery system. Structure and luminescence
      characterizations were implemented using X-ray diffraction and UV/X-ray
      spectroscopies, respectively. The results show that this technique is reliable
      and applicable to combinatorial study of powder materials with high synthesis
      temperature.

PMID- 16283806
TI  - Parallel microwave-assisted library of imidazothiazol-3-ones and imidazothiazin-4
      ones.
AB  - A methodology for the generation of a microwave-assisted parallel library and its
      conversion into a second library is described. A 24-membered library of
      substituted 4(5)-sulfanyl-1H-imidazoles was generated and subsequently converted
      into a second library of bicyclic imidazo[5,1-b]thiazol-3-ones and imidazo[5,1
      b]thiazin-4-ones. The first library was generated using a three-component
      reaction and transformed into a daughter library with a polymer-supported
      coupling agent. The procedure involved the use of an array of expandable reaction
      vessels, which can accommodate pressure buildup due to microwave heating without
      loss of volatile solvents or reagents. Library generation time for each library
      was 16 min.

PMID- 16283807
TI  - Sector spin coating for fast preparation of polymer libraries.
AB  - The feasibility of sector spin coating (or combinatorial spin-coating) is
      demonstrated (i.e., spin coating of various samples onto one single substrate
      using a metal template to divide the substrate into sectors). Film thickness
      increases in an angular direction against the sense of rotation. In the radial
      direction, the film thickness is constant within 2%. A library of 8 poly(methyl
      methacrylate)/polystyrene-blends with varying composition was spin coated and
      subsequently analyzed using automated atomic force microscopy: 24 measurements
      could be performed within 72 min. The contact angles of a library of 16
      polyoxazoline diblock copolymers were measured using one substrate with 16 spin
      coated sectors. Forty-eight measurements could be performed within 50 min. On the
      basis of the surface energies calculated using the Owens-Wendt-Rath-Kaeble
      method, the library can be divided into three groups of polymers: those
      containing a dispersive nonyloxazoline block, those containing a polar
      phenyloxazoline block, and those containing neither.

PMID- 16283808
TI  - A concise and diversity-oriented strategy for the synthesis of benzofurans and
      indoles via Ugi and Diels-Alder reactions.
AB  - A one-pot synthesis of diverse benzofurans and indoles from readily available
      starting materials was achieved via the sequential Ugi four-component reaction,
      intramolecular Diels-Alder reaction, and oxidative aromatization.

PMID- 16283809
TI  - Diversity oriented synthesis of tricyclic compounds from glycals using the
      Ferrier and the Pauson-Khand reactions.
AB  - Diversity oriented synthesis of tricyclic compounds was achieved using a
      combination of the Ferrier reaction and the Pauson-Khand reaction. Ferrier
      reaction was effected using NbCl5, and the Pauson-Khand reaction was carried out
      using Co2(CO)8, acetonitrile-dimethoxyethane. Michael additions using various
      alkyl, aryl, and heterocyclic thiols were also performed successfully. The
      Ferrier, Pauson-Khand, and Michael addition reactions were found to be highly
      diastereoselective.

PMID- 16283810
TI  - Deazapurine solid-phase synthesis: combinatorial synthesis of a library of
      N3,N5,C6-trisubstituted pyrrolo[3,2-d]pyrimidine derivatives on cross-linked
      polystyrene bearing a cysteamine linker.
AB  - Solid-phase methodology for the preparation of pyrrolo[3,2-d]pyrimidine-6
      carboxylates with diversity at the N3 pyrmidine nitrogen has now been elaborated
      to allow for the generation of pyrrolopyrimidine libraries with members
      possessing diversity at the N3, N5, and C6 positions. The diversification of the
      N5 position was achieved by treating the parent resin-bound pyrrolo[3,2
      d]pyrimidines 3 with an alkyl halide in the presence of Cs2CO3 in DMF.
      Modification of the C6 carboxylate of resin-bound pyrrolopyrimidines 3-5 was
      first achieved by hydrolysis of the benzyl ester using LiOH in a mixture of
      THF/H2O/MeOH. Further alteration of the C6 position of resin-bound pyrrolo[3,2
      d]pyrimidine-6-carboxylic acids 6-8 was then performed by activation with
      triphosgene and treatment with an amine to furnish resin-bound pyrrolo[3,2
      d]pyrimidine-6-amides. Twenty-two pyrrolo[3,2-d]pyrimidines 1a-v with different
      substituents at the N3, N5, and C6 positions were obtained in yields of 21-83%
      and purities of 61-98% after cleavage from the solid support.

PMID- 16283812
TI  - The influence of force magnitude on intrusion of the maxillary segment.
AB  - The purpose of this study was to determine whether the magnitude of intrusive
      force to the maxillary incisors influences the rate of incisor intrusion or the
      axial inclination, extrusion, and narrowing of the buccal segments. Twenty
      patients between the ages of nine and 14 years who needed at least two mm of
      maxillary incisor intrusion were assigned to one of two equal groups. In group 1
      patients, the teeth in the maxillary anterior segment were intruded using 40 g,
      whereas in group 2 patients, 80 g was used. Records were taken from each patient
      at the beginning and end of intrusion. There was no statistically significant
      difference between the 40- and 80-g groups in the rate of incisor intrusion, or
      the amount of axial inclination change, extrusion, and narrowing of the buccal
      segments.

PMID- 16283813
TI  - Treatment of skeletal open bite with a device for rapid molar intrusion: a
      preliminary report.
AB  - An open bite is one of the most difficult malocclusions the clinician has to deal
      with. In recent years, interest has increased regarding mechanics that reduce
      dependency upon patient compliance for success. Some patient-independent
      mechanism for molar intrusion or vertical control is desirable. The rapid molar
      intruder (RMI) appliance consists of two elastic modules that are secured to
      orthodontic bands on the upper and lower first molars. Vertical forces from these
      modules typically produce intrusion of the permanent molars in four to six
      months. The RMI modules may be used in the mixed dentition or incorporated in
      full-fixed mechanics in the permanent dentition. To avoid buccal flaring of the
      molars, these modules should be attached to a transpalatal arch and a mandibular
      lingual arch. Case reports are provided to stimulate interest in further
      investigation of the properties of this appliance.

PMID- 16283814
TI  - Apical root resorption of maxillary first molars after intrusion with zygomatic
      skeletal anchorage.
AB  - The aim of this study was to evaluate radiographically the apical root resorption
      of maxillary first molars after their intrusion was done using zygomatic
      miniplates as skeletal anchorage in open-bite cases. The study group comprised 16
      consecutively treated open-bite cases who had received special titanium
      miniplates in their zygomatic bones for use as anchorage to apply orthodontic
      intrusive forces to the maxillary posterior region. The control group consisted
      of 16 patients, who were matched regarding age, sex, and treatment duration but
      who had undergone fixed orthodontic treatment without intrusion mechanics for
      molars. Tooth lengths were measured on pretreatment, and posttreatment panoramic
      radiographs of all patients and mesiobuccal and distobuccal roots of left and
      right maxillary first molars were measured on-screen using a software program.
      The difference between the pre- and posttreatment tooth lengths was defined as
      apical root resorption. Comparison of the differences in root resorption of the
      two groups using the t-test for independent samples showed a statistically
      significant difference (P = .004) only for mesial roots on the right side. But
      because the mean difference in apical root resorption was only 0.5 mm, it was
      concluded that the apical root resorption of maxillary first molars after
      intrusion was done using zygomatic skeletal anchorage was not clinically
      significant.

PMID- 16283815
TI  - Influence of sex on the perception of oral and smile esthetics with different
      gingival display and incisal plane inclination.
AB  - This study was designed to determine the esthetic perception of men and women to
      variations in upper and lower gingival display at smile and speech and to incisal
      plane tilting. Composed photographs of smile and speech with varying amounts of
      gingival exposure of the upper and lower teeth and gingiva at smile and at speech
      and with varying degrees of incisal plane tilting were rated for attractiveness
      by two groups of lay people. The images were presented as male or female images.
      A total of 300 questionnaires, including 7500 images, were evaluated by 100
      subjects. The results showed that images were scored as less attractive as the
      amount of upper and lower gingival display was increased during smile and speech.
      The amount of gingival exposure graded in the esthetic range was up to one mm for
      the upper incisors and zero mm for the lower incisors. Incisal plane tilting was
      graded as unesthetic when above two degrees of deviation from the horizontal.
      Male and female evaluators scored images differently with upper gingival
      exposure. Female evaluators gave statistically significant higher scores than
      male evaluators to upper gingival exposure images at smile and speech of both
      males and females, suggesting that females are more tolerant of upper gingival
      exposure. Images were scored differently when presented as male or female images.
      Female images were scored lower by both male and female evaluators, suggesting
      that additional efforts should be taken in female patients to achieve an esthetic
      result.

PMID- 16283816
TI  - Orthodontic bracket shear bond strengths produced by two high-power light
      emitting diode modes and halogen light.
AB  - The aim of this in vitro study was to compare the shear bond strength of
      orthodontic brackets cured with two different high-power light-emitting diode
      (LED) polymerization modes with traditional halogen polymerization. A total of
      forty-five extracted human premolar teeth were randomly divided into three
      groups. Each group consisted of 15 teeth mounted in an acrylic block. Following a
      standard enamel etching protocol, orthodontic brackets were cured on the first
      group of teeth with fast-mode LED, the second group with soft-start mode LED, and
      on the last group with a halogen light. After bonding, the shear bond strengths
      of the brackets were tested with a universal testing machine. The results showed
      that brackets cured with soft-start mode LED produced the highest shear bond
      strengths (23.86 +/- 6.20 MPa). No significant difference was found between fast
      mode LED (17.14 +/- 5.75 MPa) and the halogen group (17.38 +/- 5.41 MPa) (P >
      .05). The LED is effective for bonding metal brackets to teeth, and the soft
      start mode gives higher bond strengths than the fast mode.

PMID- 16283817
TI  - The effect of porcelain surface conditioning on bonding orthodontic brackets.
AB  - The purpose of this study was to evaluate the effects of a new self-etching
      primer/ adhesive used to enhance the shear strength of orthodontic brackets
      bonded to porcelain surfaces. Forty-five porcelain maxillary central incisor
      teeth were used in the study. The teeth were divided randomly into three groups:
      group I (control), the porcelain teeth were etched with 37% phosphoric acid
      followed by a sealant and the brackets were bonded with a composite adhesive;
      group II, the porcelain teeth were microetched and hydrofluoric acid and silane
      applied and metal brackets were then bonded with the composite adhesive; and
      group III, the porcelain teeth were etched with phosphoric acid and a self
      etching primer/adhesive applied before bonding. Brackets precoated with the
      adhesive were used on all three groups of teeth. All teeth were stored for 24
      hours at 37 degrees C before debonding. The results of the analysis of variance
      (F = 10.7) indicated that there was a significant difference (P = .001) between
      the three groups. The mean shear bond strengths of conventional bonding using a
      37% phosphoric acid and sealant was 4.4 +/- 2.7 MPa, whereas that of microetching
      followed by the application of hydrofluoric acid and silane was 11.2 +/- 4.7 MPa,
      and for the new self-etching primer/adhesive it was 10.3 +/- 5.3 MPa. The last
      two groups had the highest bond strength values and were not significantly
      different from each other.

PMID- 16283818
TI  - Implementing the CanMEDSTM physician roles in rural specialist education: the
      Multi-Speciality Community Training Network.
AB  - CONTEXT: Changing medical education to realign it with societal needs has become
      a renewed priority in many countries. Advanced training in rural settings to
      prepare physicians to better serve rural areas has received particular attention
      around the world. Such initiatives are usually targeted at primary care
      practitioners. Few initiatives have been designed to enhance specialist training
      in a rural setting, let alone adapt specialist competency frameworks such as the
      CanMEDSTM roles of the Royal College of Physicians and Surgeons of Canada to non
      urban medical education. ISSUE: We describe an innovation in medical training for
      rural competence for specialist physicians using the CanMEDS framework near
      London, Ontario, Canada. Since 1997, the University of Western Ontario has
      established its Multi-Specialty Community Training Network (MSCTN) to provide
      rural and regional training opportunities for specialty residents in anaesthesia,
      general surgery, internal medicine, paediatrics, obstetrics and psychiatry. It
      became the first program in Canada to fully adapt the new CanMEDS roles into
      learning objectives and evaluations. LESSONS LEARNED: Competency-based frameworks
      like CanMEDS are important because they provide a comprehensive tool to organize
      outcome-based curricula. The CanMEDS roles framework has been very useful in
      developing educational goals for rural/regional specialty resident rotations as
      well as forming a constructive basis for resident, preceptor, and program
      evaluations. Our experiences with this program may provide lessons for others
      planning training for specialists in rural settings, and those adopting the
      CanMEDS competency framework.

PMID- 16283819
TI  - Seeing, thinking and acting against Malaria: a new approach to health worker
      training for community empowerment in rural Gambia.
AB  - CONTEXT: In the Gambia, West Africa, Malaria is a major cause of death among
      children in rural areas. It has been estimated that in one division in the
      country malaria accounts for 40% of all deaths in children aged between one and 4
      years. Most malaria cases are managed at home assisted by primary healthcare
      workers. The strategic plan of Gambia's National Malaria Control Programme
      includes improved training and supervision of all health care providers, at all
      levels, and increased community awareness in order to reduce the malaria burden
      by 50% before 2007. ISSUE: A malaria in-service training program for Community
      Health Nurses (CHNs) working at village level was piloted in 2004. The program
      includes a computer-based training (CBT) package, the first of its kind for
      health professionals in Gambia. The education program is part of a larger
      initiative funded by the Gates Malaria Partnership, that aims to increase
      community involvement in malaria control. The objective of the course is to
      enable CHNs to facilitate the change process. The curriculum was informed by a
      reference group and stakeholder input. Interviews and evaluation forms were used
      to gather information about learner experience and learning preferences.
      ANALYSIS: The CBT package was well received. Learners reported wanting more
      computer instruction, but felt they had gained confidence. There was resistance
      from other health professionals regarding the development of information
      technology skills in CHNs. This related to the perceived role and status of CHNs,
      as well as confidence in their ability. Some modifications of the CBT package
      were necessary, including the reworking of some activities and language. LESSONS
      LEARNED: There are issues related to sustainability and resource implications
      that need to be addressed. Opportunities exist to expand e-learning in the Gambia
      for pre-service CHNs and other professionals. An investigation into the viability
      of reproducing this module as a generic planning tool for allied health workers
      and other extension workers at community level will be undertaken.

PMID- 16283820
TI  - The Rural Physician Associate Program: new directions in education for
      competency.
AB  - The Rural Physician Associate Program (RPAP) has 34 years experience in training
      1097 medical students as independent distance learners in a 36 week, community
      based continuity primary care experience. This program has been successful in
      preparing competitive students who select primary care residencies and return to
      rural practice. The RPAP program has been based on traditional apprentice-style
      clinical teaching with the support of computer-based resources to enhance
      distance learning. However while the clinical exposure and development of medical
      skills was strong, there were weaknesses in evidence-based medicine and managing
      healthcare, and inconsistencies in community or population health learning. New
      directions in the educational program for RPAP are described that have been or
      are being developed to address the competencies as outlined by the Accreditation
      Council on Graduate Medical Education. They include online and other resources,
      preceptor education and support, interactive journaling and cases, electronic
      portfolios, community projects, observed structured clinical exams and
      examinations. Ongoing challenges to competency-based education include developing
      meaningful measures and tools to assess competence for areas such as
      professionalism or systems-based practice; providing faculty development toward
      being able to practice, teach and evaluate students with an understanding of the
      competencies; and to build in ways of practicing, learning and improving care
      that involve effective teams of health-care professionals.

PMID- 16283821
TI  - The network: towards unity for health, building a 'Star Alliance' among kindred
      organizations.

PMID- 16283822
TI  - Combined research and clinical learning make Rural Summer Studentship Program a
      successful model.
AB  - CONTEXT: Many medical schools would like to provide students with opportunities
      to learn and perform practical research and to have positive rural learning
      experiences. Rural physicians often have research ideas, but may lack the skills
      or assistance to perform the research. PROGRAM DESCRIPTION: The unique Rural
      Summer Studentship Program (RSSP) at The University of Western Ontario (Western)
      places students with preceptors in small and mid-sized communities throughout
      Southwestern Ontario where they have an opportunity to perform rural health
      research, combined with clinical learning, for 8 weeks in the summer after the
      first or second year of medical school. Secretarial coordination, research
      assistant support and senior faculty supervision were provided. OUTCOMES: From
      1999-2003 inclusive, 44 students have participated including eight who
      participated over two summers. Projects were carried out in more than 20
      communities with over 30 preceptors. Already, two students have had their
      research published in peer-reviewed journals and six have presented at major
      conferences. Participating students indicated an increase in interest in rural
      and regional medicine and in their knowledge of rural and regional medicine and
      patient care. They rated the value of RSSP highly as part of their medical
      education, even compared with other electives/selectives. CONCLUSION: The RSSP
      model developed at Western provides a highly rated, successful combination of
      supported medical student research and clinical learning with preceptors in small
      and mid-sized communities.

PMID- 16283823
TI  - The education part of telehealth.

PMID- 16283824
TI  - Evaluation of a required statewide interdisciplinary Rural Health Education
      Program: student attitudes, career intents and perceived quality.
AB  - INTRODUCTION: A shortage of healthcare providers in West Virginia led to creation
      of a statewide, community-based program with a required three-month rural
      experience for most state-sponsored health professions students. Project
      Description: Initiated using funding from the W. K. Kellogg Foundation and
      expanded using both state funds and Area Health Education Center support, the
      West Virginia Rural Health Education Partnerships (WVRHEP) program impacts
      institutions of higher learning, 50 counties, and 332 training sites, and all
      students in state-funded health professions schools. A longitudinal database has
      been constructed to study program effects on students' reported attitudes,
      service orientation, and career intents. METHODS: Baseline data are collected
      from medical students, and students in all disciplines provide feedback on
      rotations and information about career intents, social responsibility, and
      attitudes towards rural practice. RESULTS: Data indicate an association between
      perceived quality of the rural experience and increased interest in rural health,
      social responsibility and confidence in becoming part of the community. Medical
      students may tend to rate social responsibility higher after completion of the
      first rural rotation. Students who anticipate practice in smaller towns also tend
      to rate the quality of the rotation higher, to anticipate careers in primary
      care, and to acknowledge social responsibility. CONCLUSION: As WVRHEP program
      graduates who have completed these surveys enter practice, both personal and
      community-specific program characteristics may be identified which strengthen
      interest in rural practice. The predictive validity of intermediate outcomes of
      attitudes and career intents in forecasting the ultimate outcomes of recruitment
      and retention may be studied.

PMID- 16283825
TI  - Educational and health services innovation to improve care for rural Hispanic
      communities in the USA.
AB  - BACKGROUND: Access to comprehensive and quality healthcare services is difficult
      for socioeonomically disadvantaged groups in rural regions. Barriers to health
      care for rural Latinos include lack of insurance, language barriers and cultural
      differences. For the Latino immigrant population in rural areas, barriers to
      access are compounded. HEALTH NEEDS OF RURAL AREAS: THE CASE OF WALHALLA, SC: The
      town of Walhalla, South Carolina, USA, is a rural community located in Oconee
      County, the northwest corner of the state. Disparities exist between rural and
      urban residents in several health categories, and these disparities illustrate
      the need to provide competent, appropriate and affordable healthcare to rural
      populations. The Hispanic population of Oconee has dramatically increased in the
      past decade, and the majority of these immigrants have no health insurance and
      have limited access to health services. DESIGNING A PROGRAM TO FIT THE COMMUNITY-
      THE "WALHALLA EXPERIENCE": The purpose of the Accessible and Culturally Competent
      Health Care Project (ACCHCP) is to provide care for underserved populations, in
      Oconee County, South Carolina while providing rural educational opportunities for
      health services students. Funded by the Health Resources and Services
      Administration of DHHS, the program is designed to offer culturally appropriate,
      sensitive, accessible, affordable and compassionate care in a mobile clinic
      setting. In this interdisplinary program, nurse practitioners, health educators,
      bilingual interpreters, medical residents and Clemson University students and
      professors all played key roles. Women in the community also serve as promotoras
      or lay health advisors. The program is unique in using educational initiatives
      and innovative strategies for bringing health care to this underserved community
      and offers important information for rural healthcare initiatives targeting
      minority groups. This article reports on the challenges and successes in the
      development and implementation of the ACCHCP program in Walhalla, South Carolina.

PMID- 16283826
TI  - Advances in rural medical education in three countries: Canada, The United States
      and Australia.
AB  - INTRODUCTION: This article documents a number of rural medical education
      initiatives in Australia, Canada and the United States. A typology is created
      reflecting the centrality the rural mandate and characterizing different features
      of each school's program. Interviews with school officials are drawn on to
      reflect the challenges these schools face. METHOD: Seven schools noted for their
      rural programs were selected from the three countries and interviews were
      conducted with senior officials. The interview data was supplemented by published
      material on the schools. RESULTS: The Typology: Three kinds of school are
      distinguished: Mixed Urban/Rural Schools (University of Washington, US, the
      University of British Columbia, Canada, and Flinders University, Australia);
      DeFacto Rural Schools (University of New Mexico, US and Memorial University,
      Canada) and Stand Alone Rural Schools (James Cook University, Australia and the
      Northern Ontario School of Medicine, Canada). The Pipeline Approach: All of the
      schools adopted in varying degrees a pipeline approach to meeting the need for
      rural doctors focusing on: (a) early recruitment; (b) admissions; (c) locating
      clinical education in rural settings; (d) rural health focus to curriculum; and
      (e) support for rural practice. CONCLUSION: The analysis does not strongly favor
      one model over others, although the Stand-Alone Rural schools had more
      opportunities to adopt innovative curricula reflecting rural health issues and to
      foster positive views of rural practice. Government funding targeting rural
      health needs will remain critical in the development of all these programs.

PMID- 16283827
TI  - Student-developed problem-based learning cases: preparing for rural healthcare
      practice.
AB  - INTRODUCTION: The need for health professionals is acute throughout rural
      communities worldwide. The Rural Health Interdisciplinary Program (RHIP)
      successfully trains health professional students for practice in rural USA.
      Student-developed problem-based learning (PBL) cases are a central feature of the
      RHIP and an important educational focus of learning. METHODS: This retrospective
      study was designed to describe 222 PBL cases developed by health professional
      students in the RHIP. The analysis focused on the extent to which student
      developed cases reflect demographics and health conditions of rural New Mexico,
      as well as how successfully cases reflect rural interdisciplinary healthcare
      issues and practices. RESULTS: The PBL cases do reflect rural New Mexico in terms
      of population demographics, certain health problems and complexity of health
      issues. The cases appear address interdisciplinary, rural clinical concerns.
      However, the cases are less effective at raising issues related to public health,
      financial, legal and ethical issues, and other non-medical health topics.
      CONCLUSIONS: In order to strengthen attention to non-medical issues, PBL groups
      should have broad interdisciplinary membership, special case development
      training, and faculty encouragement to address a wide variety of health-related
      topics. Student-developed PBL cases appear to be an interesting way for health
      professional students to learn about rural healthcare issues and could be used in
      a variety different educational settings.

PMID- 16283830
TI  - Age of menopause and menopausal symptoms in HIV-infected women.
AB  - The objective of this study was to examine the median age of menopause, factors
      associated with postmenopausal status, and the prevalence of menopausal symptoms
      in HIV-infected women. We surveyed 120 HIV-infected women between 40 and 57 years
      old who attended an inner city infectious diseases clinic. Ninety-five percent of
      the women surveyed were African American and almost half of the women (44%) had
      used methadone, heroin, cocaine, marijuana, or a combination of these drugs
      within the past 6 months. Eighty-seven percent had smoked cigarettes at least
      some time during their life and 45% drank alcohol between the ages of 40 and 49
      years old. Thirty women were postmenopausal (having no menstrual periods in the
      previous 12 consecutive months), 31 were perimenopausal (having 1-11 periods
      within the previous 12 months), and 59 were premenopausal (having 12 or more
      periods within the previous 12 months). The median age of menopause was 50 years
      old (95% confidence interval = 49, 53). In a multivariate model, methadone use
      within the past 6 months was associated with postmenopausal status. We did not
      find an association between postmenopausal status and body mass index, number of
      pregnancies, CD4 cell counts, HIV viral load, individual and grouped
      antiretroviral therapies, cigarette smoking, and current or past oral
      contraceptive use. In multivariate analysis, postmenopausal status was associated
      with hot flashes and cocaine use was associated with vaginal dryness.

PMID- 16283828
TI  - The impact of medical students on rural general practitioner perceptors.
AB  - INTRODUCTION: As universities rely more heavily on rural GPs to precept medical
      students, the formation of symbiotic partnerships benefiting students,
      universities and GPs, becomes imperative. In order to develop and consolidate
      these partnerships Universities must understand who their rural GP preceptors are
      and how precepting impacts on them. METHODS: A review of the literature was
      undertaken to determine the significant themes of student impacts from articles
      where conclusions were clearly based on empirical findings. RESULTS: Forty-three
      articles were included in the final review, but only nine specifically looked at
      impacts on rural GPs. Impacts were categorised into six domains: personal; time;
      patient care; professional relationships and professional development; business
      and infrastructure; and recognition and remuneration. CONCLUSIONS: Literature
      specifically addressing the impact of precepting on rural GPs is scarce. Further
      studies are required to evaluate the relationship between the quality of teaching
      delivered to students, the type and length of student attachments and the likely
      impacts on rural GPs.

PMID- 16283831
TI  - Deaths of HIV-positive men in the context of assisted reproduction: five case
      studies from a single center.
AB  - Provision of reproductive services to individuals infected with HIV-1 is gaining
      popular acceptance and is generally endorsed by specialists in reproductive
      medicine. In the situation in which the male is HIV positive and the female
      partner is not infected, a large body of evidence has demonstrated that the use
      of assisted reproductive technology is effective for achieving pregnancy, while
      eliminating the risk of viral transmission to the mother and fetus. No reports
      have documented the well-being of the HIV-infected partners subsequent to seeking
      fertility services. In the current report, we document the cases of five HIV
      positive men who died secondary to complications of HIV infection shortly after
      participating in the assisted reproduction program for HIV-1-serodiscordant
      couples at Columbia University. Three of these couples successfully achieved
      pregnancy and live birth, including one set of triplets, and one case of
      posthumous conception; the fourth case resulted in the cryopreservation of all
      embryos after the sudden death of the male before the time of embryo transfer;
      the fifth couple failed to conceive. None of the deaths, which occurred within a
      few months to 2 years from initial consultation, were related to infertility
      treatment. The demographic and social statuses of these patients were not
      different from the general population of men seeking assisted reproduction in our
      clinic. Regarding the HIV infection status of these cases, three patients had a
      longer duration of infection compared to the general population of men in our
      cohort, and one had a significantly lower CD4 cell count. All five men had stable
      HIV viral loads, and were determined by their primary care providers to be
      clinically healthy at the time of entry into the program for assisted
      reproduction. The untimely deaths of these patients underscores the importance of
      the thoughtful consideration of the complex issues involved in family planning
      for these individuals, including advanced directives for the use of cryopreserved
      gametes and embryos, and the social, emotional, and practical issues for the
      children and surviving partners subsequent to the death of the HIV-positive
      parent.

PMID- 16283832
TI  - Life stress and adherence to antiretroviral therapy among HIV-positive
      individuals: a preliminary investigation.
AB  - The present study sought to investigate the impact of life stress on treatment
      adherence and viral load of HIV-positive individuals. Three different aspects of
      life stress were examined in this investigation (perceived stress, acute life
      events unrelated to the HIV illness, and HIV-related acute life events).
      Furthermore, we examined whether these relationships were moderated by depressive
      severity, self-esteem, and neuroticism. Participants (n = 24) were treatment-
      seeking HIV-positive individuals who completed a series of questionnaires for
      this investigation. The majority of the participants in this sample were middle
      aged, Caucasian males who identified themselves as either homosexual or bisexual,
      had contracted HIV via sexual contact, and met criteria for AIDS (mean CD4 count
      = 324). This sample was highly self-selected and varied from the county HIV
      positive population in terms of gender, ethnicity, and HIV risk factor.
      Information on their adherence and viral load was collected from their medical
      records 6 to 9 months after completion of the psychological measurements. Results
      indicated that perceived stress, but not acute events, prospectively predicted
      adherence. Moreover, marginal trends suggested that depressive symptoms and
      neuroticism moderated the effect of perceived stress on adherence. Neither
      perceived stress nor acute life events were associated with viral load.

PMID- 16283833
TI  - Incidence and impact of posttraumatic stress disorder and comorbid depression on
      adherence to HAART and CD4+ counts in people living with HIV.
AB  - Recent research suggests that the presence of posttraumatic stress disorder
      (PTSD) and depressive symptoms is independently related to abnormal hormone
      levels, inadequate medication adherence, and faster HIV disease progression.
      Although PTSD and depression occur comorbidly at high rates, the impact of both
      disorders on adherence and disease progression has not been examined. The present
      study examined the impact of PTSD and comorbid depression on CD4 cell counts and
      medication adherence in 58 male and 11 female (36% African American) HIV-positive
      individuals recruited from an AIDS service organization. Results revealed that
      participants high in depressive symptoms had lower CD4 cell counts and were less
      likely to adhere to their medication regimens than participants high in PTSD
      symptoms and those high in comorbid symptomatology. The present results suggest
      that the presence of depressive symptoms may be responsible for the observed
      impact of PTSD on people living with HIV (PLWH), and that failure to examine
      comorbid disorders may not adequately address the impact of clinical symptoms on
      people living with HIV.

PMID- 16283834
TI  - Preventing HIV among Latino and African American gay and bisexual men in a
      context of HIV-related stigma, discrimination, and homophobia: perspectives of
      providers.
AB  - HIV-related stigma, discrimination, and homophobia impede community-based efforts
      to combat HIV disease among Latino and African American gay and bisexual men.
      This commentary highlights ways to address these social biases in communities of
      color in Los Angeles, California, from the perspectives of staff from HIV
      prevention programs. Information was collected from HIV prevention program staff
      participating in a 2-day symposium. The outcomes from the symposium offer
      strategies for developing and implementing HIV prevention services for Latino and
      African American gay and bisexual men, which include: (1) addressing social
      biases present in a community that can hinder, and even prohibit, utilization of
      effective HIV prevention programs; (2) recasting HIV prevention messages in a
      broader social or health context; (3) developing culturally appropriate HIV
      prevention messages; (4) exploring new modalities and venues for delivering HIV
      prevention messages that are appropriate for gay and bisexual men of color and
      the communities in which they live; and (5) broadening the target of HIV
      prevention services to include service providers, local institutions and
      agencies, and the community at-large. These strategies underscore the need to
      consider the social and contextual factors of a community when designing and
      implementing HIV prevention programs.

PMID- 16283835
TI  - Effects of a treatment adherence enhancement program on health literacy, patient
      provider relationships, and adherence to HAART among low-income HIV-positive
      Spanish-speaking Latinos.
AB  - The impact of an adherence enhancement program for low income HIV-infected
      Spanish-speaking Latinos on health literacy, patient-provider relationships, and
      adherence to HAART was examined. Evaluations were conducted at baseline, 6 weeks,
      and 6 months for participants (n = 85) randomly assigned to either the
      intervention group or a comparison group; 69 (81%) remained in the study for the
      entire 6-month duration. The intervention group scored significantly better than
      the comparison group on 3 of 5 measures of HIV health literacy at 6 weeks and on
      2 of 5 measures, at 6 months. While there was a weak trend for the intervention
      group to report an increase in self-efficacy of medication adherence management,
      baseline to 6 weeks, no other changes were significant. Perceptions of the
      quality of relationship and communications with their HIV-treating physicians
      improved both at 6 weeks (p = 0.04) and at 6 months (p < 0.001). The comparison
      group showed little change baseline to 6 weeks and baseline to 6 months. While
      there was a trend for the pilot group to report better medication adherence,
      these differences were not statistically significant. Further evaluation of the
      impact of this adherence enhancement program is needed.

PMID- 16283836
TI  - Antiretroviral therapy and sexual behavior: a comparative study between
      antiretroviral- naive and -experienced patients at an urban HIV/AIDS care and
      research center in Kampala, Uganda.
AB  - We examined whether use of antiretroviral (ARV) therapy is associated with
      increased sexual risk behavior in a cross-sectional study of patients undergoing
      ARV therapy (ARV experienced) compared to patients not undergoing ARV therapy
      (ARV-naive) attending an urban HIV clinic in Kampala, Uganda. Sexual behavior
      during the prior 6 months and sexually transmitted disease (STD) treatment was
      determined by face-to-face structured interviews. Multiple logistic regression
      was used to identify independent correlates of sexual activity, multiple sexual
      partners, inconsistent condom use, and STD treatment during the prior 6 months.
      Three hundred forty-seven (48%) of the 723 respondents reported a history of
      sexual intercourse in the 6 months prior to the interview (sexually active).
      Receipt of ARV therapy was not associated with a significantly higher likelihood
      of being sexually active (adjusted odds ratio [AOR], 2.0 95% confidence interval
      [CI], 0.3-9.9). Among both ARV-experienced and ARV-naive persons who were
      sexually active, 35% (120) reported one or more casual sexual partners in
      addition to a main partner (no difference by ARV status). Consistent condom use
      with spouse, regular, casual, and commercial partners was reported by 57%, 65%,
      85%, and 85% of the sexually active respondents, respectively. The ARV
      experienced respondents were more likely to report consistent condom use with
      their spouses than were ARV-naive respondents (OR 2.82 95% CI 1.74-4.6). ARV
      experienced respondents were more likely than ARV-naive respondents to have
      disclosed their HIV status to their spouses (OR 1.57 95% CI 1.07-2.30).The ARV
      experienced group was more likely to report STD treatment in the prior 6 months
      (AOR 2.62 95% CI 1.8-3.83) than the ARV-naive group. The findings suggest that in
      this population, use of ARV therapy was not associated with risky sexual behavior
      in the prior 6 months. Still, recall and social desirability biases remain
      important limitations in interpreting these conclusions.

PMID- 16283838
TI  - Groups want Ryan White renewed.

PMID- 16283837
TI  - Knowledge, attitudes, behaviors, and perceptions of risk related to HIV/AIDS
      among Chinese university students in Hunan, China.
AB  - The purpose of this paper is to describe HIV/AIDS knowledge, attitudes, and
      perceptions and identify personal risk behaviors among undergraduate students in
      China. A descriptive, cross-sectional survey of 1326 students between ages 17
      through 28 was conducted in 2002. Results indicated that students held
      considerable misconceptions about HIV transmission by casual contact and needle
      sharing as well as stigmatizing attitudes about injection drug use, homosexuality
      and HIV-positive women who bear children. Results indicated that 14% of Chinese
      university students are sexually active and risk behaviors tended to increase
      with age. Additionally, 24% of the students considered themselves to be at
      moderate to very high risk of contracting HIV and 40% of sexually active students
      never used condoms. Therefore, it is important to design HIV prevention
      strategies that target university students in China.

PMID- 16283839
TI  - Initial results for PRO 140.

PMID- 16283840
TI  - HIV in central Florida Latinos rising.

PMID- 16283842
TI  - First prize: ureteral segmental replacement revisited.
AB  - BACKGROUND AND PURPOSE: Long strictures of the proximal ureter are difficult to
      manage, and circumferential replacement with various natural and synthetic
      materials has been unsuccessful. We sought to use cultured autologous cells
      seeded onto graft material for proximal-ureteral replacement. Additionally, we
      wished to determine if urothelial cell-seeded de-epithelialized small bowel would
      generate adequate ureteral replacement. MATERIALS AND METHODS: Three sets of
      experiments were performed. First, autologous pig-bladder smooth-muscle and
      urothelial cells were expanded in culture on large sheets of multilayer small
      intestinal submucosa (SIS). These sheets were then tubularized and used to
      replace a 5-cm segment of proximal ureter in pigs. Second, autologous cells
      harvested from the bladders of Beagle dogs were cultured and seeded on porcine
      ureteral acellular matrix, which was used to replace a 3-cm segment of ureter in
      dogs. Segments were wrapped in omentum to enhance vascularity. Third, a de
      epithelialized small-bowel segment seeded with autologous bladder-epithelial
      cells was transversally retubularized (Monti) into a 4-cm ureteral replacement.
      Follow-up studies consisted of retrograde pyelography, serum chemistry assays,
      hematoxylin/eosin studies, and immunohistopathologic examination using antibodies
      against alpha-smooth-muscle actin and pancytokeratin AE1-AE3. RESULTS: Coculture
      of urinary-tract cells on large segments of SIS failed to create adequate
      ureteral replacement. All grafts were contracted and stenotic, with complete
      obstruction of the ipsilateral renal unit. Similar results were seen in the
      Beagles. Despite clinical obstruction and gross contraction of the graft, a
      circumferential muscular ureteral wall lined with multilayer transitional
      epithelium was present. Urotheliumseeded de-epithelialized Monti bowel segments
      resulted in patent ureteral replacement without hydroureteronephrosis and with
      normal renal function, serum electrolytes, and acid-base balance. However, bowel
      mucosa fully regenerated, with multilayer transitional epithelium growing
      adluminally in continuity with the proximal and distal anastomotic sites.
      CONCLUSIONS: Seeding of ureteral grafts with autologous bladder cells does not
      promote success in two largeanimal models using different xenogenic acellular
      matrices. However, muscle and urothelium regeneration occurs with ureteral
      acellular matrix in the dog. Urothelium-seeded de-epithelialized Monti bowel
      segments may be an acceptable substitute for long proximal ureteral segments.
      Further technical refinements are required to replace the bowel mucosa completely
      with normal urothelium.

PMID- 16283843
TI  - Second prize: simple method for achieving renal parenchymal hypothermia for pure
      laparoscopic partial nephrectomy.
AB  - PURPOSE: We describe the development of an innovative device and simple technique
      for achieving renal parenchymal hypothermia during temporary renal-vascular
      occlusion for pure laparoscopic partial nephrectomy. MATERIALS AND METHODS: The
      experiment was conceived in four phases: phase 1: design, manufacture, and
      testing of the cooling coil; phase 2: proof of concept in nonsurvival porcine
      surgery; phase 3: experimental porcine survival surgery; and phase 4: human
      trials. RESULTS: Phase 1 testing confirmed that the coil cooled adequately.
      During phase 2, the average time required for the renal parenchyma to cool to 15
      degrees C was 10.7 minutes, providing an average hypothermic window (15 degrees 
      24 degrees C) of 30.3 minutes. When recooling was required (parenchymal
      temperature 24 degrees C), temperatures returned to below 15 degrees C in 3
      minutes. The core body temperature dropped an average of 1.48 degrees C. Phase 3
      demonstrated an average parenchymal temperature of 11.7 degrees C after a mean
      cooling time of 9.3 minutes. Temperatures remained below 24 degrees C for an
      average of 26.7 minutes. Recooling took 3 minutes, and in no procedure did the
      renal parenchyma temperatures ever return to >24 degrees C prior to reperfusion.
      The core body temperature dropped an average of 2.20 degrees C. At 48 hours after
      reperfusion, selective renal-vein blood was obtained for creatinine assay, and
      the kidneys were harvested. Creatinine results were not statistically different
      in the treated and control groups. Blinded pathologic analysis confirmed a
      protective effect using our cooling system. CONCLUSION: Our method is simple,
      effective, and reproducible.

PMID- 16283844
TI  - Third Prize: Comparison of radical nephrectomy, laparoscopic microwave
      thermotherapy, cryotherapy, and radiofrequency ablation for destruction of
      experimental VX-2 renal tumors in rabbits.
AB  - BACKGROUND AND PURPOSE: Currently available minimally invasive renal tumor
      ablation procedures include cryotherapy, radiofrequency ablation, and microwave
      thermotherapy. In this study, we investigated the ability of these three
      approaches to destroy experimental renal tumors in rabbits. The mechanism of
      potential tumor metastasis was also explored. MATERIALS AND METHODS: The VX-2
      tumor line is an aggressive rabbit epidermoid tumor with a high metastatic
      potential. An initial experiment comparing cooled-tip microwave thermotherapy
      with cryotherapy and radical nephrectomy for treatment of small VX-2 tumors
      revealed that all microwave-treated rabbits had local recurrence and that several
      also had diffuse intraperitoneal carcinomatosis. In view of these results, a
      second experiment was performed in which 45 New Zealand White rabbits were
      implanted laparoscopically with VX-2 xenografts underneath the kidney capsule and
      divided into five groups of 9 each. The test groups were microwave thermotherapy
      with a 3.5-mm cooled-tip probe, microwave thermotherapy with a 3.5-mm noncooled-
      tip probe, radiofrequency ablation with a 1.5-mm cooled-tip probe, radiofrequency
      ablation with a 1.5- mm non-cooled tip probe, and cryotherapy with a 2.3-mm
      cryoprobe. The control groups were five rabbits that were not treated, five
      rabbits with tumors that had the tumor pierced with a probe but were untreated,
      and five rabbits that underwent nephrectomy after piercing of the tumor.
      Treatment was initiated 5 days after tumor implantation. One month later, all
      animals were euthanized and autopsied. RESULTS: At 5 days after tumor
      implantation, laparoscopic inspection revealed no visible peritoneal metastases.
      At 1 month, in the cooled and non-cooled microwave-thermotherapy groups,
      carcinomatosis occurred in five and six of nine animals, respectively. In
      comparison, carcinomatosis was detected in two of nine animals in the cryotherapy
      group at autopsy. With respect to cooled and non-cooled radiofrequency ablation,
      carcinomatosis was observed in four of nine rabbits in each group. In the control
      groups, none of the animals with unpierced tumors exhibited carcinomatosis, while
      carcinomatosis was seen in two of the five rabbits with tumor violated by
      piercing and in three of the five rabbits that underwent immediate nephrectomy
      after piercing of the tumor. CONCLUSION: Carcinomatosis occurred most frequently
      in animals treated with microwave thermotherapy, followed by radiofrequency
      ablation, and lastly cryoablation. The simple act of piercing a highly aggressive
      tumor can result in local spread. More disconcerting, and less well understood,
      is why certain ablative modalities appear to increase the rate of intraperitoneal
      spread.

PMID- 16283845
TI  - Third prize: Prostaglandin E(2)-3 receptor is involved in ureteral contractility
      in obstruction.
AB  - BACKGROUND AND PURPOSE: We previously found that prostaglandin (PG) E2 contracts
      acutely obstructed ureters while relaxing normal ureters. This study investigated
      the procontractile effects of the PG EP3 receptor in PGE(2)-mediated
      contractility in obstructed and normal porcine ureters. MATERIALS AND METHODS: We
      created unilateral ureteral obstruction laparoscopically using titanium clips in
      farm pigs; the contralateral ureters were dissected as sham controls. Ureters
      were harvested 48 hours post-obstruction, cut into 5-mm segments, and suspended
      in water-jacketed tissue baths in Krebs buffer. Tissues were equilibrated for 1
      hour, and spontaneous contractile rates were recorded. After 2 hours of
      incubation in Krebs (controls) or pertussis toxin (G(alpha)i signaling-protein
      inhibitor [EP-3 blockade]) 500 ng/mL, a concentration- response curve (10(-9) M
      10(-5) M) to PGE(2), PGF(2), sulprostone (EP 3 agonist), or 0.01% ethanol
      (vehicle) was created (N = 4). RESULTS: In the normal ureters, PGE(2) relaxed
      both pertussis toxin-treated and control tissues. In obstructed segments, PGE(2)
      increased contractions by 60%; this was reversed by pertussis toxin to a 67%
      reduction in contractile rate. In both obstructed and contralateral segments,
      sulprostone induced contractility in the controls; this was attenuated by
      pertussis toxin. The PGF(2) produced a contractile effect in both the controls
      and the pertussis toxin-treated segments, demonstrating the selectivity of
      pertussis toxin for EP3 receptors. CONCLUSION: Our data indicate that the EP3
      receptor is involved in hypercontractility during ureteral obstruction. However,
      it may not be the sole factor behind the condition-dependent effect of PGE(2).

PMID- 16283846
TI  - Performance and safety of holmium: YAG laser optical fibers.
AB  - BACKGROUND AND PURPOSE: Lower-pole ureteronephroscopy requires transmission of
      holmium:YAG energy along a deflected fiber. Current ureteroscopes are capable of
      high degrees of deflection, which may stress laser fibers beyond safe limits
      during lower-pole use. We hypothesized that optical fiber and safety measures
      differ among manufacturers. MATERIALS AND METHODS: Small (200-273-microm) and
      medium-diameter (300-400-microm) Ho:YAG fibers were tested in a straight and 180
      degrees bent configuration. Energy transmission was measured by an energy
      detector. Fiber durability was assessed by firing the laser in sequentially
      tighter bending diameters. The fibers were bent to 180 degrees with a diameter of
      6 cm and run at 200- to 4000-mJ pulse energy to determine the minimum energy
      required to fracture the fiber. The bending diameter was decreased by 1-cm
      increments and testing repeated until a bending diameter of 1 cm was reached. The
      maximum deflection of the ACMI DUR-8E ureteroscope with each fiber in the working
      channel was recorded. The flow rate through the working channel of the DUR-8E was
      measured for each fiber. RESULTS: The mean energy transmission differed among
      fibers (P < 0.001). The Lumenis SL 200 and the InnovaQuartz 400 were the best
      small and medium-diameter fibers, respectively, in resisting thermal breakdown (P
      < 0.01). The Dornier Lightguide Super 200 fractured repeatedly at a bend diameter
      of 2 cm and with the lowest energy (200 mJ). The other small fibers fractured
      only at a bend diameter of 1 cm. The Sharplan 200 and InnovaQuartz Sureflex 273T
      were the most flexible fibers, the Lumenis SL 365 the least. The flow rate was
      inversely proportional to four times the power of the diameter of the fiber.
      CONCLUSIONS: Optical performance and safety differ among fibers. Fibers transmit
      various amounts of energy to their cladding when bent. During lower-pole
      nephroscopy with the fiber deflected, there is a risk of fiber fracture from
      thermal breakdown and laser-energy transmission to the endoscope. Some available
      laser fibers carry a risk of ureteroscope damage.

PMID- 16283847
TI  - Robotic versus conventional laparoscopic skill acquisition: implications for
      training.
AB  - BACKGROUND AND PURPOSE: Despite the growing interest in surgical robotics, very
      little study has been done regarding the acquisition of the skills needed to
      perform robotic surgery safely. The purpose of this study was to determine
      whether skills are transferred between conventional laparoscopy and robotically
      assisted surgery. SUBJECTS AND METHODS: Intracorporeal knot tying was used for
      evaluating laparoscopic skills for time and error performance. Twenty medical
      students without any laparoscopic experience were randomized into two groups.
      Group A initially performed knot tying with conventional laparoscopic
      instruments, were trained with the daVinci Robotic System, and then performed
      knot tying with conventional laparoscopy. Group B performed knot tying with
      robotics, trained with standard laparoscopy, and completed post-training knot
      tying with robotics. Pretraining and post-training tasks were videotaped and
      analyzed using a detailed scoring system by one independent referee, who was
      blinded to the subjects' experience. RESULTS: Pre-training knot tying was faster
      with robotics (4.4 v 9.9 minutes; P < 0.001). The mean composite scores were 27.4
      for group A and 57.4 for group B (P = 0.09), and the error scores were 57.1 and
      42.1 (P = 0.29), respectively. Post-training time for knot completion decreased
      to 6.7 minutes and 3.4 minutes for groups A and B, respectively. Composite scores
      increased significantly, from 27.4 to 66.1 for group A and 57.4 to 81.8 for group
      B. Error scores decreased to 32.9 for group A (P = 0.1) and 16.2 in group B (P =
      0.02). CONCLUSIONS: There appears to be reciprocal transfer of skills between
      conventional laparoscopy and robotically assisted surgery. However, this
      transference is incomplete. Our results suggest that training with either
      technique or conventional laparoscopy is superior to training with robotics
      alone.

PMID- 16283848
TI  - Evaluation of a novel modified suture material designed to facilitate
      intracorporeal knot tying during laparoscopic surgery.
AB  - BACKGROUND AND PURPOSE: Laparoscopic intracorporeal knot tying in minimally
      invasive surgery is an advanced skill. Mastering this skill is an arduous process
      with a long learning curve. While recent advances in instrumentation have allowed
      easier suturing and tying, until now, no attempts have been made to modify the
      suture material in order to facilitate this process. We present an evaluation of
      a novel modified suture material designed to allow inexperienced surgical
      residents to tie intracorporeal knots laparoscopically using conventional
      laparoscopic needle drivers. SUBJECTS AND METHODS: Surgical residents with no
      prior experience in laparoscopic surgery were invited to take part in this
      investigation. Each of the 14 participants was given a 10-minute demonstration of
      laparoscopic intracorporeal knot tying and then allowed a mentored practice
      session of 10 minutes. In the first trial, they were then randomized to tie a
      laparoscopic knot with either a standard or a modified dry suture. Time and
      accuracy scores were recorded. They then performed the same task with the other
      type of suture. On the second trial, wet standard and modified sutures were used,
      and the order of the sutures used in the first trial was reversed. RESULTS: The
      average time taken to tie an intracorporeal knot laparoscopically was
      significantly less when the modified suture was used in both dry and wet
      conditions (162.71 +/- 10.79 seconds v 270.86 +/- 22.76 seconds; P = 0.0039, and
      123.29 +/- 4.70 seconds v 247.57 +/- 23.17 seconds; P = 0.0032, respectively). No
      significant difference in accuracy scores was noted with the two sutures.
      CONCLUSIONS: Our modified suture design allowed inexperienced surgical residents
      to perform intracorporeal laparoscopic knot tying on average faster than the
      standard suture did. The concept of modifying suture design to facilitate
      laparoscopic suturing and knot tying deserves further investigation and
      development.

PMID- 16283849
TI  - Comparison of running and interrupted vesicourethral anastomoses in a porcine
      model.
AB  - PURPOSE: To compare running and interrupted suturing techniques for porcine
      vesicourethral anastomosis with regard to procedure time, histopathologic
      effects, and leakage. MATERIALS AND METHODS: Twelve domestic pigs were randomized
      to a running (N = 6) or an interrupted (N = 6) vesicourethral anastomosis with
      polyglycolic acid sutures. In each case, the bladder was drained for 7 days. A
      cystogram was performed immediately after completion of each anastomosis and on
      postoperative days 7 and 30. Animals were sacrificed on postoperative day 30, and
      the area of the anastomosis was excised en bloc for histopathologic evaluation.
      RESULTS: All procedures were completed laparoscopically. The mean operative time
      for continuous and interrupted suturing were 27.5 and 36.8 minutes, respectively
      (P = 0.3324). A significant learning curve was noted for both anastomoses, with
      operative times decreasing with experience in both groups. There was no
      difference in anastomotic leakage. Histopathology examination revealed more
      muscle-layer fibrosis in the interrupted- suture group than in the continuous
      suture group, with a mean score of 2.17 and 1.67, respectively (P = 0.0325).
      CONCLUSIONS: Both continuous and interrupted vesicourethral anastomoses are
      feasible. In this in-vivo porcine comparison, there was no difference with
      respect to procedure time or anastomotic leakage. However, histopathologic
      grading demonstrated greater muscle fibrosis in the interrupted-suture group.

PMID- 16283850
TI  - Controlled survival study of the effects of Tisseel or a combination of FloSeal
      and Tisseel on major vascular injury and major collecting-system injury during
      partial nephrectomy in a porcine model.
AB  - PURPOSE: We report the results of a controlled survival study in a porcine model
      investigating Tisseel or a combination of FloSeal and Tisseel in dealing with
      vascular and collecting-system injury during partial nephrectomy. MATERIALS AND
      METHODS: We performed an open right lower-pole partial nephrectomy on 15 large
      female pigs. The defect was repaired using standard open techniques (N = 5;
      controls), Tisseel only (N = 6; group I), or FloSeal followed by Tisseel (N = 4;
      group II). A Jackson-Pratt drain was placed. Nephrectomy and retrograde
      pyelography were performed at 1 week. RESULTS: Operative times were shorter in
      both study groups, achieving statistical significance in group I (P = 0.008).
      Warm-ischemia times were significantly improved in both study groups (P = 0.029
      and P = 0.00005 in groups I and II, respectively). Time to hemostasis was
      significantly shorter in group II only (P = 0.002) but approached significance in
      Group I as well (P = 0.09). Estimated blood loss was not significantly different
      from the controls in either group. When Tisseel was placed alone after hilar
      control, hematoma formation under the Tisseel was noted on release of the hilar
      clamp. After 1 week, there was one urinoma and three urine leaks in the control
      group. In group I, there was one urinoma and four urine leaks, and there was only
      one urine leak and no urinomas in group II. There were no hematomas in any of the
      groups. CONCLUSIONS: Tisseel alone is not adequate for either hemostasis or
      management of major collecting-system injury. FloSeal capped with Tisseel appears
      sufficient to control major vascular and collecting-system injuries without
      adjunctive surgical measures. A proposed technique for laparoscopic partial
      nephrectomy without reconstructive techniques is presented that warrants clinical
      study.

PMID- 16283851
TI  - Evaluation of hydrogel tissue sealant in porcine laparoscopic partial-nephrectomy
      model.
AB  - BACKGROUND AND PURPOSE: Laparoscopic partial nephrectomy (LPN) is technically
      challenging with a steep learning curve, primarily because techniques used to
      control bleeding on the cut surface of the kidney can be ineffective,
      inconsistent, or challenging. Hemostatic techniques can include intracorporeal
      suturing, vascular coagulation (argon-beam coagulator, bipolar cautery, laser),
      and application of various tissue sealants. There is no uniformity of opinion
      regarding which hemostatic technique is optimal for this application. CoSeal, a
      hydrogel (Baxter Healthcare Corp, Deerfield, IL), has been effective following
      vascular surgery but has not been applied to a partial-nephrectomy model. We
      evaluated the effectiveness of this hydrogel in controlling bleeding and sealing
      the collecting system by comparing it with intracorporeal suturing and fibrin
      sealant (Tisseel; Baxter) in a porcine laparoscopic partial-nephrectomy model.
      MATERIALS AND METHODS: Bilateral synchronous upper-pole partial nephrectomies
      were performed in two groups of 18 farm pigs, and the three hemostatic techniques
      (suturing, Tisseel, CoSeal) were applied. In the first group, partial
      nephrectomies were performed and the pigs sacrificed 3 days postoperatively
      (acute group). In the second group, the pigs were euthanized 6 weeks
      postoperatively (chronic group). In both groups, weight, blood pressure,
      estimated blood loss, weight of the partial and completion nephrectomy specimen,
      presence/ absence of urinary leak on retrograde study, histopathologic findings,
      and complications were recorded. RESULTS: The mean weight, blood pressure,
      estimated blood loss, histopathology findings, and weight of the partial and
      completion nephrectomy specimens were similar in the three groups. CoSeal did not
      adhere well to the renal parenchyma compared with Tisseel. All three animals in
      the acute CoSeal group and three of the six pigs in the sutured group had small
      urinary leaks during retrograde ureteral study, whereas none of the pigs in the
      fibrin-glue cohort had urinary leaks. There was one complication (urinary leak)
      in the CoSeal group, necessitating sacrifice of the animal on postoperative day 8
      because of sepsis. CONCLUSIONS: CoSeal is not as effective as fibrin glue in
      adhering to the cut renal surface and sealing the collecting system during
      laparoscopic partial nephrectomy.

PMID- 16283852
TI  - Laparoscopic suturing: effect of instrument handling on suture strength.
AB  - BACKGROUND AND PURPOSE: In open surgery, handling of suture at any position other
      than the end is discouraged because of evidence that handling deforms and weakens
      the material. The limited operative field of laparoscopic surgery necessitates
      repeated instrument handling of suture, and the effect of such handling has not
      been investigated. We assessed the effect of trauma imposed on various suture
      materials by laparoscopic needle holders and forceps. Also, the ideal suturing
      technique (interrupted v continuous) according to the physical characteristics of
      the suture material and the optimal length for laparoscopic sutures were
      determined. MATERIALS AND METHODS: Sutures of 2-0 and 3-0 polyglactin 910 and 2-0
      poliglecaprone 25 were tested. Controlled damage was inflicted by grasping the
      suture for 1 second between the jaws of either toothed laparoscopic grasping
      forceps or a laparoscopic needle holder at a pressure of 45 MPa. Blind physical
      testing was then performed using a computer-controlled tensile testing system.
      The length and proportion of suture extension prior to breaking and the tensile
      strength were measured. Samples of undamaged and controlled damaged specimens,
      before and after breakage, were examined by scanning electron microscopy (SEM).
      RESULTS: The mean percentage extension in the control group was 46.3 mm for 3-0
      Monocryl, 26.3 mm for 3-0 Vicryl, and 28.1 mm for 2-0 Vicryl. The mean tensile
      strengths were 47.9 N, 42.4 N, and 70.4 N for 3-0 Monocryl and 3-0 and 2-0
      Vicryl, respectively. The 3-0 Monocryl and 3-0 Vicryl had significantly reduced
      tensile strength after damage compared with control sutures, whereas 3-0 Vicryl
      and 2-0 Vicryl had significantly impaired extension. After infliction of
      controlled damage with laparoscopic needle holders, the percent extension of
      damaged sutures was significantly less than that of undamaged sutures. Tensile
      strength was significantly lower for 3-0 Vicryl and 3-0 Monocryl after damage
      than before. The handling of Monocryl by laparoscopic needle holders and graspers
      produced punched-out defects and scratch marks, respectively. A number of damaged
      2-0 and 3-0 Vicryl samples from the laparoscopic needle holder group showed
      disruption or unravelling of the braided filaments. CONCLUSION: We expect that
      our results underestimate the potential effect on suture strength and extension
      inflicted by laparoscopic suturing. The exact length of suture material cannot be
      recommended from the findings. However, interrupted sutures should be preferred,
      particularly for long suture lines. In addition, the findings support the use of
      laparoscopic graspers in preference to needle holders. The combination of a
      grasper in one hand and needle holder in the other is ideal. Finally, urologists
      initially embarking on laparoscopic reconstruction must take meticulous care in
      their suturing technique and, in particular, the number of times and force with
      which the suture is grasped.

PMID- 16283853
TI  - The Boatman's knot: a single knot for renal-vein ligation during laparoscopic
      nephrectomy: description of technique and evaluation of feasibility and safety.
AB  - BACKGROUND AND PURPOSE: The endovascular stapler is the standard of care for
      renal-vein ligation during nephrectomy, but recently, some reports have addressed
      the need for lowering the costs in the operating room. The authors describe the
      first use of "boatman's knot" in renal-vein ligation during laparoscopic
      nephrectomy and tests of its safety and feasibility. MATERIALS AND METHODS:
      Sixteen bilateral laparoscopic nephrectomies were performed in female pigs. On
      the right side, the renal vein was ligated with the boatman's knot, and on the
      left side, the vein was ligated with conventional intracorporeal technique. The
      knots were performed by the same surgeon at initial laparoscopic training. The
      time required to tie the knots was measured. After bilateral nephrectomy, a
      midline incision was created, and the bursting pressure of the knots was measured
      with a manometer by saline infusion into the vena cava. RESULTS: The average knot
      completion time was 45 seconds (range 30-50 seconds), and the average time needed
      to carry out the conventional suture was 202.5 seconds (range 186-228 seconds).
      After renal-vein transection, there was complete hemostasis in all cases. The
      mean bursting pressure was 179.9 mm Hg (range 126-304 mm Hg). In five cases, the
      rupture site was in a lumbar vein previously sutured, while in three cases, the
      rupture happened in the vena cava itself. CONCLUSION: The boatman's knot is
      feasible, safe, easy to learn, and faster than conventional intracorporeal
      suturing. This technique may replace the endovascular stapler. However, its
      clinical applicability remains to be determined.

PMID- 16283854
TI  - Cytokine response to surgical stress: comparison of pure laparoscopic, hand
      assisted laparoscopic, and open nephrectomy.
AB  - BACKGROUND AND PURPOSE: Laparoscopic surgery has been shown to induce less immune
      suppression than open surgery, presumably because there is less tissue trauma, a
      factor that may impact oncologic-disease control. The objective of this study was
      to compare the cytokine and stress response associated with pure laparoscopic,
      hand-assisted laparoscopic (HAL), and open nephrectomy. MATERIAL AND METHODS:
      Fifteen female farm pigs (45-50 kg) underwent transperitoneal laparoscopic,
      handassisted (HAL), or open nephrectomy (N = 5 in each group). At 1, 4, 24, and
      48 hours post-nephrectomy, blood and peritoneal fluid samples were collected for
      measurement of tumor necrosis factor (TNF) alpha, interleukin (IL)-1beta, and IL
      6 using enzyme-linked immunosorbent assay (ELISA) techniques. Body temperature
      and serum glucose and cortisol were also measured. RESULTS: No evidence of
      perioperative infection was detected in any animal through temperature and
      glucose monitoring. Operating time and blood loss were comparable among the three
      groups. Peak serum cortisol concentrations were significantly higher in the HAL
      group than in the pure laparoscopic group at 24 hours (P = 0.02). Serum TFNalpha
      concentrations were significantly lower in the pure laparoscopy group (40 +/- 6
      pg/mL) than in the HAL and open-nephrectomy groups (81 +/- 6 pg/mL and 83 +/- 17
      pg/mL, respectively; P < 0.05), although no differences between groups were found
      in the serum IL-1beta and IL-6 concentrations. Peritoneal IL-1beta was
      significantly higher in the HAL than in the open-nephrectomy group (2993 +/- 507
      pg/mL and 733 +/- 185 pg/mL, respectively; P = 0.05). Peritoneal IL-6 was
      significantly lower in the pure laparoscopy group (694 +/- 234 pg/mL) than in the
      open-surgery group (1668 +/- 312 pg/mL) (P = 0.04). CONCLUSION: Pure laparoscopic
      surgery in pigs elicits a less-robust cytokine response than HAL or open
      nephrectomy with respect to serum TNFalpha and peritoneal IL-6 concentrations,
      perhaps reflecting less impairment of the immune system. Clinical confirmation is
      required, and the implications with regard to oncologic tumor surveillance in
      humans require further study.

PMID- 16283862
TI  - Cost-effectiveness of rosuvastatin compared with other statins from a managed
      care perspective.
AB  - OBJECTIVE: The objective of this study was to identify the most cost-effective
      statin or combination of statins, from the perspective of a managed care payer.
      METHODS: A decision-analytic model compared the cost-effectiveness of titration
      to goal with atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin,
      and simvastatin in patients with elevated low-density lipoprotein cholesterol
      (LDL-C). Effectiveness measures included the percentage change from baseline LDL
      C and high-density lipoprotein cholesterol (HDL-C), and the percentage of
      patients achieving National Cholesterol Education Program (NCEP) Second Adult
      Treatment Panel (ATP II) LDL-C goals. Direct medical costs were calculated based
      on drug, physician, and laboratory resource use, multiplied by wholesale
      acquisition costs for drugs and the 2005 Medicare reimbursement rates for
      services. A Monte Carlo simulation tested the sensitivity of results to model
      efficacy inputs. RESULTS: In the base-case analysis, rosuvastatin dominated
      atorvastatin, pravastatin, and simvastatin. Generic lovastatin dominated
      fluvastatin. The incremental (absolute) reduction in LDL-C, increase in HDL-C,
      and increase in patients to goal with rosuvastatin compared with lovastatin were
      16%, 3%, and 27%, respectively. Incremental costs per additional 1% reduction in
      LDL-C, 1% increase in HDL-C, and patient to goal with rosuvastatin versus
      lovastatin were $8, $41, and $436, respectively. A wide variety of assumptions
      were assessed and Monte Carlo sensitivity analyses were conducted. Findings were
      most sensitive to the cost of lovastatin. CONCLUSION: Rosuvastatin dominates
      atorvastatin, pravastatin, and simvastatin because it is more effective and less
      costly, and it may be considered cost-effective compared with generic lovastatin.
      The most cost-effective two-statin formulary contained lovastatin and
      rosuvastatin.

PMID- 16283857
TI  - Essential role of Rac1/NADPH oxidase in nerve growth factor induction of TRPV1
      expression.
AB  - Nerve growth factor (NGF) regulates the nociceptive properties of a subset of
      small diameter sensory neurons by increasing the expression of the heat-sensing
      transient receptor potential (TRP) channel, TRPV1. This action involves
      activation of the tyrosine kinase receptor (Trk) A/p38 MAPK pathway. Recent
      studies indicate that activation of TrkA promotes superoxide generation via NADPH
      oxidase. In this study, we determined whether the NADPH oxidase pathway is
      involved in NGF-stimulated TRPV1 expression using a rat pheochromocytoma 12 line
      and rat dorsal root ganglion neurons. Treatment of these cells with NGF (100
      ng/mL) increased TRPV1 protein expression (approx. twofold) but not mRNA. This
      increase was mimicked by H(2)O(2) and attenuated by catalase and inhibitors of
      NADPH oxidase. NGF stimulated NADPH oxidase activity, while 24 h exposure further
      increased expression of the Rac1 and gp91(phox) subunits of the holoenzyme.
      Inhibition of NADPH oxidase by transient transfection of a dominant negative Rac1
      mutant (RacN17) plasmid blocked NGF-stimulated TRPV1 protein expression, while
      expression of a constitutively active Rac1 increased basal and NGF-stimulated
      TRPV1 levels. Inhibition of NADPH oxidase activity also attenuated NGF-dependent
      p38 MAPK activation. We conclude that the Rac1/NADPH oxidase pathway regulates
      p38 activation and TRPV1 expression which aids in the maintenance of peripheral
      neuron integrity and pain perception.

PMID- 16283863
TI  - Economic burden of patients with anemia in selected diseases.
AB  - OBJECTIVE: To examine the economic impact of patients with anemia in selected
      diseases. METHODS: A retrospective cohort design was used to estimate the
      differences in costs between anemic and nonanemic patients. The analysis used
      administrative claims data (1999-2001) from a US population to assess direct
      costs and disability and productivity data (1997-2001) to estimate indirect
      costs. Adult patients with a diagnosis of rheumatoid arthritis (RA), inflammatory
      bowel disease (IBD), chronic obstructive pulmonary disease (COPD), chronic kidney
      disease (CKD), cancer, or congestive heart failure (CHF) were identified. Costs
      were estimated using a generalized linear model, adjusting for age, sex,
      comorbidities, and disease severity. The adjustment variables for disease
      severity were based on ICD-9, HCPCS, or pharmacy codes. These costs were
      projected to a 1-million-member, similar population. RESULTS: The percentage of
      anemia patients varied among conditions (6.9-26.1%); the CKD population had the
      highest prevalence. CKD anemic patients incurred the greatest average annual
      direct costs ($78,209), followed by CHF ($72,078) and cancer ($60,447). After
      adjusting for baseline characteristics including severity, the difference in
      direct costs between anemic and nonanemic patients decreased for all diseases;
      CHF patients incurred the greatest adjusted cost difference between anemic and
      nonanemic ($29,511), followed by CKD ($20,529) and cancer ($18,418). Unmeasured
      severity and coding bias may account for a portion of the differences in the
      adjusted cost. CONCLUSION: Anemia may substantially increase health-care costs at
      a level that is economically very relevant, despite the fact that these patients
      may comprise only one tenth of the overall anemic population.

PMID- 16283864
TI  - Impact of computer-generated personalized goals on cholesterol lowering.
AB  - OBJECTIVES: The National Cholesterol Education Program (NCEP) has enhanced public
      awareness of the importance of cholesterol in the development of heart disease,
      yet most patients with cardiovascular disease (CVD) do not know or achieve their
      low-density lipoprotein cholesterol (LDL-C) goals. This randomized, controlled
      trial was designed to evaluate the impact of a system that provides uniquely
      formatted laboratory results to patients with CVD on their changes in LDL-C
      levels. METHODS: Eighty patients with CVD were randomized to receive standard
      care or the intervention inclusive of a computer-generated, 11''x17'' color
      poster depicting an individual's LDL-C status and goals along with personalized
      steps to aid in goal achievement. Cholesterol profiles were obtained at baseline
      and 6 months after enrollment. Physicians received standard laboratory reports
      and were blinded to the randomization. RESULTS: There were no significant
      differences between patient groups in age, education level, race, baseline
      cholesterol levels, comorbidities, or percentage of patients in each group who
      met their NCEP goal at baseline. Patients receiving intervention tools had
      significant reductions in LDL-C from baseline compared with patients in the
      control group. Intervention patients who did not meet NCEP goals at baseline had
      the greatest reduction in LDL-C, with a mean change from baseline of -21.5 mg/dL
      (P<0.001) whereas standard care patients had no significant change in the LDL-C
      levels (-4.6 mg/dL, P=0.28). At study close, 73% of intervention patients
      reported that their posters remained displayed on their refrigerator. CONCLUSION:
      This unique and personalized intervention resulted in the LDL-C lowering benefit
      among patients with CVD comparable to that of lipid lowering agents.

PMID- 16283865
TI  - An economic evaluation of triptan products for migraine.
AB  - OBJECTIVE: A composite outcome measure in migraine treatment assessment is useful
      to clinical decision-makers and payers as it can provide a more accurate
      reflection of effectiveness and allows for more complete modeling of economic
      value. The objective of this study was to compare the total triptan cost to treat
      100 migraine patient attacks and the cost per successfully treated patient
      (CPSTP) for six marketed triptans using a composite measure of effectiveness, the
      "successfully treated" migraine (defined as requiring only one triptan dose to
      treat one migraine attack during a 24-h period). METHODS: This analysis was
      conducted from the perspective of the payer. Clinical data were abstracted from a
      rigorous, published meta-analysis. Two-hour response and pain-free response were
      used in conjunction with the recurrence rate reported in the meta-analysis to
      calculate the number of doses used by treatment successes and failures. The
      average wholesale price per dose was then used to calculate total triptan cost.
      RESULTS: Of the nine oral triptan doses compared, eletriptan 40 mg was associated
      with both the lowest total triptan cost for treating 100 migraine attacks ($1560)
      and with the lowest CPSTP ($56.39). CONCLUSIONS: The relative CPSTP rankings for
      migraine therapies are dependent on the definition of treatment success and
      relative pricing. The results of this study support the use of eletriptan for the
      treatment of acute migraine based on the model assumptions. This study can be
      used to assist in formulary considerations and offers a model that can be adapted
      by health-care decision-makers.

PMID- 16283866
TI  - A comparison of self-selectivity corrections in economic evaluations and outcomes
      research.
AB  - OBJECTIVE: Two alternative selectivity correction methods have been widely
      applied in the health economics literature: the sample selection model (SSM) and
      the multipart model (MPM). The difference between these two approaches results
      from their initial assumptions about the distribution of error terms. Because the
      distributional assumptions cannot be theoretically verified, the usefulness of
      the methods can only be evaluated by real world comparison. This article reviews
      and empirically tests the two alternative selectivity correction methods to give
      a reality-based evaluation. METHODS: Using a randomized sample of patients as the
      "gold standard," the SSM and MPM are applied to a nonrandomized sample of
      patients with an identical set of dependent and independent variables. By
      comparing the actual estimates of the two methods, we evaluate the robustness of
      the two approaches. RESULTS: The results show that neither method is empirically
      robust in replicating the results of the randomized trial. There is no consistent
      pattern in the coefficients from either selectivity-correction method for
      replicating the coefficients in the randomized sample. CONCLUSIONS: Researchers
      should be cautious in applying these correction methods, and any conclusions
      based on these approaches may need to be qualified.

PMID- 16283868
TI  - Plantar pressure in off-loading devices used in diabetic ulcer treatment.
AB  - Four off-loading devices used for the treatment of diabetic forefoot ulcers were
      compared: a custom-molded insole shoe, a cast MABAL shoe, a prefabricated
      pneumatic walking brace, and a bivalved total contact cast (BTCC). It was
      anticipated that all devices would significantly reduce forefoot plantar pressure
      compared with a control shoe. Sixteen healthy volunteers participated. Plantar
      pressures were evaluated using the Pedar system, while walking speed was
      determined using an optoelectric timer. Peak pressure (PP) of ten plantar areas
      and pressure-time integral for the first metatarsal area were analyzed
      statistically using a repeated measures analysis of variance. Forefoot pressures
      were significantly reduced compared with the control shoe for all devices
      (p<0.001). PP was most reduced (by 65.8%) for the BTCC, and pressure-time
      integral was most reduced for the BTCC and cast MABAL shoe. Small but significant
      differences between devices in walking speed (p<0.05) could not explain the
      substantial PP differences between the different devices. Although all off
      loading devices resulted in a significant reduction of forefoot plantar pressure,
      devices differed significantly in the magnitude of pressure reduction. Further
      research will have to reveal the level of off-loading sufficient for effective
      treatment of diabetic ulcers.

PMID- 16283867
TI  - Effectiveness of recombinant human platelet-derived growth factor for the
      treatment of diabetic neuropathic foot ulcers.
AB  - The goal of this study was to estimate the effectiveness in actual clinical
      practice of recombinant human platelet-derived growth factor (rhPDGF) for the
      treatment of diabetic neuropathic foot ulcer (DNFU). Previously published pivotal
      trials have shown that by the 20th week of care 35 percent more ulcers healed in
      the group randomized to receive rhPDGF than those who did not receive rhPDGF
      (i.e., a relative risk [RR] of about 1.35). This represents an estimate of the
      efficacy of rhPDGF under the tightly controlled conditions of randomized clinical
      trials. Treatment effectiveness under standard clinical practice was estimated in
      a retrospective cohort study, controlling for treatment selection bias using
      propensity scores. We noted 24,898 individuals with a DNFU, of whom 9.6 percent
      received rhPDGF. We successfully created a propensity score model that evenly
      balanced many wound characteristics between those who received rhPDGF and those
      who did not. We created five groups, which varied from those least likely to
      receive rhPDGF to those most likely to receive rhPDGF. The RR, controlling for
      the propensity, to receive rhPDGF for a healed wound after treatment with rhPDGF
      as compared with standard care was 1.32 (1.22, 1.38). With respect to amputation,
      the RR for undergoing amputation after receiving rhPDGF was 0.65 (0.54, 0.78) as
      compared with those who did not receive rhPDGF. Within the limitations of our
      study, rhPDGF is more effective than standard therapy in both helping a wound to
      heal and preventing amputation, and its effect is similar to the efficacy
      estimates from previously published randomized controlled trials.

PMID- 16283869
TI  - A simple in vitro model for investigating epithelial/mesenchymal interactions:
      keratinocyte inhibition of fibroblast proliferation and fibronectin synthesis.
AB  - Hypertrophic scarring and graft contracture are major causes of morbidity after
      burn injuries. It is well established that application of a split-thickness skin
      graft reduces scarring and contraction, and cultured epithelial autografts have a
      similar effect. To investigate the influence of keratinocytes on fibroblast
      proliferation and fibronectin synthesis, we used an in vitro separated co-culture
      model in which epithelial sheets were cultured above fibroblast monolayers
      without physical contact. We also investigated the response of fibroblasts to
      keratinocyte-conditioned medium (KCM) obtained from confluent and subconfluent
      keratinocyte monolayers. Both cultured epithelial sheets, composed of adherent
      fully confluent keratinocytes, and their conditioned medium, reduced fibroblast
      proliferation. However, KCM from subconfluent keratinocytes stimulated fibroblast
      proliferation at low concentrations while inhibiting it at higher concentrations,
      indicating that keratinocytes can produce both mitogenic and growth-inhibiting
      factors for fibroblasts. KCM, but not epithelial sheet co-culture, also inhibited
      fibroblast fibronectin synthesis. This indicates regulation of fibroblast
      phenotype by soluble factors released by the keratinocyte and also suggests that
      there is a dialogue between keratinocytes and fibroblasts with respect to
      fibronectin production. We conclude that this separated co-culture model is a
      simple way to study epithelial/mesenchymal communication particularly with
      respect to the role of the fibroblast in wound healing.

PMID- 16283870
TI  - Hyperbaric oxygen stimulates cell proliferation and normalizes multidrug
      resistance protein-2 protein localization in primary rat hepatocytes.
AB  - Hyperbaric oxygen therapy (HBO) has been used for many clinical treatments,
      including primary liver non-function. However, the cellular mechanism by which
      HBO treatment ameliorates liver function is not understood. Therefore, the
      purpose of this study was to elucidate this cellular mechanism using primary
      cultured rat hepatocytes in in vitro studies. Hepatocytes were treated with HBO
      at 1 day after plating, and the morphological and functional characteristics of
      bile canaliculi formed in cultured hepatocytes were observed by time-lapse
      microscopy. Multidrug resistance protein-2 localization was observed by confocal
      laser microscopy. In cultured hepatocytes, the labeling index in the HBO group at
      2 days after treatment was significantly higher than that in the control group.
      In addition, the proliferating cellular nuclear antigen level in the HBO group
      was significantly higher than that in the control group. The contraction of the
      bile canaliculi in the HBO group was slower than in the control group and the
      dilatation of bile canaliculi in the HBO group was much larger than in the
      control group. Multidrug resistance protein-2 in the HBO group was localized at
      the apical membrane. These results show that HBO stimulates hepatocytes to
      proliferate and HBO normalizes multidrug resistance protein-2 localization to the
      apical membrane, which could dilate bile canaliculi.

PMID- 16283871
TI  - Hyperoxia and angiogenesis.
AB  - We hypothesized that tissue hyperoxia would enhance and hypoxia inhibit
      neovascularization in a wound model. Therefore, we used female Swiss-Webster mice
      to examine the influence of differential oxygen treatment on angiogenesis. One
      milliliter plugs of Matrigel, a mixture of matrix proteins that supports but does
      not itself elicit angiogenesis, were injected subcutaneously into the mice.
      Matrigel was used without additive or with added vascular endothelial growth
      factor (VEGF) or anti-VEGF antibody. Animals were maintained in hypoxic,
      normoxic, or one of four hyperoxic environments: hypoxia -- 13 percent oxygen at
      1 atmosphere absolute (ATA); normoxia -- 21 percent oxygen at 1 ATA; hyperoxia --
      (groups a-d) 100 percent oxygen for 90 minutes twice daily at the following
      pressures: Group a, 1 ATA; Group b, 2 ATA; Group c, 2.5 ATA; Group d, 3.0 ATA.
      Subcutaneous oxygen tension was measured in all groups. The Matrigel was removed
      7 days after implantation. Sections were graded microscopically for the extent of
      neovascularization. Angiogenesis was significantly greater in all hyperoxic
      groups and significantly less in the hypoxic group compared with room air-exposed
      controls. Anti-VEGF antibody abrogated the angiogenic effect of both VEGF and
      increased oxygen tension. We conclude that angiogenesis is proportional to
      ambient pO(2) over a wide range. This confirms the clinical impression that
      angiogenesis requires oxygen. Intermittent oxygen exposure can satisfy the need
      for oxygen in ischemic tissue.

PMID- 16283872
TI  - Age-dependent response of primary human dermal fibroblasts to oxidative stress:
      cell survival, pro-survival kinases, and entrance into cellular senescence.
AB  - A central question in cell biology is how cells become senescent. After a finite
      number of cell divisions, normal cultured human cells enter a state of
      irreversible growth arrest, termed "replicative senescence." Alternatively,
      oxidative stress in the form of hydrogen peroxide (H(2)O(2)) can render human
      dermal fibroblasts (HDFs) nonproliferative and quiescent, a phenomenon known as
      stress-induced premature senescence (SIPS). Although critical to the
      understanding of the pathophysiological basis of many diseases, there is no
      research to date that has simultaneously examined the interactions between age,
      oxidative stress, and SIPS. Therefore, the goals of this study were to examine in
      concert the interactions between these three factors in primary HDFs, and to test
      our central hypothesis that aging lowers the ability of primary HDFs to respond
      to oxidative stress. Our data provide, for the first time, evidence that aging
      dramatically reduces the capacity of primary HDFs to respond to the challenge of
      hydrogen peroxide. Specifically, aged HDFs showed decreased cell viability,
      decreased phosphorylation (activation) of pro-survival kinases (Akt and ERK 1/2),
      and increased entrance into a senescent state when compared with their younger
      counterparts. Another important conclusion of this study is that blockade of
      transforming growth factor-beta1 had a pronounced "rescue effect" in the aged,
      preventing entrance of HDFs into cellular senescence.

PMID- 16283874
TI  - Pachydermoperiostosis: an update.
AB  - Pachydermoperiostosis (PDP) is a rare genodermatosis, characterized by
      pachydermia, digital clubbing, periostosis and an excess of affected males.
      Although an autosomal dominant model with incomplete penetrance and variable
      expression has been proved, both autosomal recessive and X-linked inheritance
      have been suggested. However, at present, genetic heterogeneity is not fully
      supported. The aim of this study is to review the clinical and pedigree data of
      68 published PDP families, including 204 patients. This analysis has confirmed an
      autosomal dominant mutation in 37 families and suggested the existence of an
      autosomal recessive form in the remaining families. The two forms may differ in
      clinical severity, intrafamilial variability and prevalence of some features.
      Additionally, the marked skewed sex ratio could not be easily explained by an X
      linked mutation, but alternative explanations (i.e. testosterone promoting
      proliferation) are discussed.

PMID- 16283873
TI  - Optimization and validation of an ischemic wound model.
AB  - Localized tissue ischemia is a key factor in the development and poor prognosis
      of chronic wounds. Currently, there are no standardized animal models that
      provide sufficient tissue to evaluate the effect of modalities that may induce
      angiogenesis, and in vitro models of angiogenesis do not mimic the complexity of
      the ischemic wound bed. Therefore, we set out to develop a reproducible ischemic
      model for use in wound-healing studies. Male Sprague-Dawley rats underwent
      creation of dorsal bipedicle skin flaps with centrally located excisional wounds.
      Oxygen tension, wound-breaking strength, wound area, lactate, and wound vascular
      endothelial growth factor (VEGF) were compared in flaps measuring 2.5 and 2.0 x
      11 cm with and without an underlying silicone sheet. We found that the center of
      the 2.0 cm flap with silicone remains in the critically ischemic range up to 14
      days without tissue necrosis (33+/-4 vs. 49+/-6 mmHg in controls). Wound healing
      and breaking strength were significantly impaired and tissue lactate from the
      center of this flap was 2.9 times greater than tissue from either nonischemic
      controls and 2.5 cm flap (0.23+/-0.05 mg/dL/mg sample vs. 0.09+/-0.02 and 0.08+/
      0.02, respectively). Vascular endothelial growth factor was 2 times greater than
      the nonischemic control. This ischemic wound model is relatively inexpensive,
      easy to perform, reproducible, and reliable. The excisional wounds provide
      sufficient tissue for biochemical and histologic analysis, and are amenable to
      the evaluation of topical and systemic therapies that may induce angiogenesis or
      improve wound healing.

PMID- 16283875
TI  - Molecular genetics of the early development of hindbrain serotonergic neurons.
AB  - The serotonergic (5HT) system plays a key role in modulating behaviors, such as
      appetite and anxiety and has been implicated in many human disorders of mood and
      mind. Recent studies have begun to identify the signaling molecules and
      transcriptional cascades governing 5HT neuron development in the hindbrain.
      Already at early stages, local differences in requirements of 5HT neuron
      development have become apparent. These studies point toward cryptic
      heterogeneity amongst 5HT neurons and suggest that 5HT neuron determination and
      differentiation may be more flexible and less absolute biologic processes than
      might have been expected. Ultimately, the intrinsic heterogeneity and
      environmental sensitivity of 5HT neurons may help explain the variability
      observed in some human behavioral disorders, such as autism spectrum disorder,
      and the less predictable behavioral consequences of fetal alcohol syndrome.

PMID- 16283879
TI  - Split hand foot malformation (SHFM).
AB  - The nomenclature describing the phenotype of missing central rays in the hand
      and/or foot in the genetics and surgical literature is heterogeneous and
      confusing. Split hand/foot malformation (SHFM) is the most common term for this
      phenotype in the genetics community; however, other names such as the offensive
      'lobster-claw malformation' and the non-specific 'ectrodactyly' are still
      utilized to describe this malformation. In this article, we briefly review the
      nomenclature associated with SHFM and its classifications.

PMID- 16283880
TI  - Assessment of the genetic causes of recessive childhood non-syndromic deafness in
      the UK - implications for genetic testing.
AB  - Approximately one in 2000 children is born with a genetic hearing impairment,
      mostly inherited as a non-syndromic, autosomal recessive trait, for which more
      than 30 different genes have been identified. Previous studies have shown that
      one of these genes, connexin 26 (GJB2), accounts for 30-60% of such deafness, but
      the relative contribution of the many other genes is not known, especially in the
      outbred UK population. This lack of knowledge hampers the development of
      diagnostic genetic services for deafness. In an effort to determine the molecular
      aetiology of deafness in the population, 142 sib pairs with early-onset, non
      syndromic hearing impairment were recruited. Those in whom deafness could not be
      attributed to GJB2 mutations were investigated further for other mapped genes.
      The genetic basis of 55 cases (38.7%) was established, 33.1% being due to
      mutations in the GJB2 gene and 3.5% due to mutations in SLC26A4. None of the
      remaining 26 loci investigated made a significant contribution to deafness in a
      Caucasian population. We suggest that screening the GJB2 and SLC26A4 genes should
      form the basis of any genetic testing programme for childhood deafness and
      highlight a number of important issues for consideration and future work.

PMID- 16283881
TI  - Characterization of an analphoid supernumerary marker chromosome derived from
      15q25-->qter using high-resolution CGH and multiplex FISH analyses.
AB  - Supernumerary marker chromosomes (SMCs) without detectable alphoid DNA are
      predicted to have a neocentromere and have been referred to as mitotically stable
      neocentromere marker chromosomes (NMCs). We report the molecular cytogenetic
      characterization of a new case with analphoid NMC derived from 15q25-->qter using
      high-resolution comparative genomic hybridization (HR-CGH) and multiplex
      fluorescence in situ hybridization analyses with various alpha-satellite DNA
      probes, all-human-centromere probe (AHC), whole chromosome painting probes, and a
      subtelomere probe. The propositus is a dysmorphic infant who, at age 3 months,
      showed accelerated growth, partial deafness, and a phenotype similar to that of
      the eight previously reported cases of distal 15q tetrasomy. Chromosome studies
      showed that he had a de novo extra SMC in 80% of cells examined. HR-CGH revealed
      rev ish enh(15)(q25qter). Molecular cytogenetic analysis and molecular DNA
      polymorphism study demonstrated that this extra SMC is an NMC containing an
      inverted duplication of the distal long arm of chromosome 15 (tetrasomy 15q25-
      >qter) which originated paternally, i.e. ish der(15)(qte-->q25::q25[neocen]-
      >qter)(AHC-, CEP15-, WCP15+, PCP15q++). This case further elucidates the
      phenotype related to tetrasomy of this specific chromosome segment and represents
      a new report of a neocentromere on distal chromosome 15q suggesting that this
      region appears to be susceptible to the formation of neocentromeres.

PMID- 16283882
TI  - Blepharophimosis and bilateral Duane syndrome associated with a FOXL2 mutation.
AB  - This case describes the novel coexistence of sporadic blepharophimosis-ptosis
      epicanthus inversus syndrome (BPES) and bilateral type I Duane syndrome in a
      female infant, with a FOXL2 mutation. Mutational analysis of FOXL2 demonstrated a
      30-nucleotide duplication (c.672(-)701dup30) within the polyalanine tract of
      FOXL2. The association of BPES and Duane syndrome represents a novel phenotype
      which may suggest a greater pleiotropic effect of FOXL2 in development. During
      the period of the 4-8th week of embryonic development, the cranial nerves, their
      nuclei and the corresponding innervation to the extraocular muscles develop, the
      extraocular muscles undergo development and differentiation. This coincides with
      the period of time that FOXL2 is expressed strongly in the developing eyelids and
      the surrounding tissues. Forkhead genes are transcription factors and likely to
      be involved in signal transduction pathways. This case expands the spectrum of
      FOXL2 mutations associated with BPES.

PMID- 16283884
TI  - Two Swedish founder MSH6 mutations, one nonsense and one missense, conferring
      high cumulative risk of Lynch syndrome.
AB  - Lynch syndrome, or hereditary non-polyposis colorectal cancer (HNPCC), is a
      cancer susceptibility syndrome caused by germline mutations in mismatch-repair
      genes, predominantly MLH1, MSH2 and MSH6. A majority of the mutations reported
      are truncating, but for MSH6, missense mutations constitute over one third. Few
      have been proven pathogenic in functional studies or shown to segregate in
      families. In this study, we show segregation of the putative pathogenic MSH6
      missense mutation c.1346T>C p.Leu449Pro with microsatellite instability-high
      Lynch syndrome-related tumours lacking MSH6 expression in a large 17th century
      pedigree. Another large family with the MSH6 nonsense c.2931C>G, p.Tyr977X
      mutation is similar in tumour spectra, age of onset and cumulative risk. These
      MSH6 families, despite their late age of onset, have a high lifetime risk of all
      Lynch syndrome-related cancers, significantly higher in women (89% by age 80)
      than in men (69%). The gender differences are in part explained by high
      endometrial (70%) and ovarian (33%) cancer risks added upon the high colorectal
      cancer risk (60%). The several occurrences of breast cancer are not due to the
      MSH6 mutations. These findings are of great importance for counselling,
      management and surveillance of families with MSH6 mutations.

PMID- 16283883
TI  - Frameshift and nonsense mutations in the gene for ATPase7B are associated with
      severe impairment of copper metabolism and with an early clinical manifestation
      of Wilson's disease.
AB  - Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism.
      The clinical phenotype of the disease is varied. It is proposed that this
      variation may be a result of differential functional disruption of ATPase7B
      (ATP7B) resulting from mutations in the gene ATP7B. We aimed to assess the
      relationship between specific mutational defects in ATP7B and divergence in the
      phenotypic expression of WD. One hundred and forty-two patients with clinically,
      biochemically and genetically diagnosed WD were included in the study. The
      phenotypic expression of WD was compared between patients with different types of
      mutations in ATP7B, detected by direct sequencing of exons 1-21 of the gene.
      Twenty-six mutations were identified in ATP7B; eleven of them were mutations
      predicted to result in the absence of a full-length normal protein
      [frameshift/nonsense mutations; classified as 'severe' mutations (SMs)], 14 were
      missense mutations (MMs) and one was a splice site mutation. Patients with one or
      two SMs on their alleles had lower serum copper and ceruloplasmin and were
      younger when the first symptoms of the disease appeared, compared with
      individuals with two MMs. The effect of SMs on the WD phenotype was dose
      dependent. It is concluded that mutations within ATP7B are very heterogeneous.
      Frameshift and nonsense mutations are associated with a severe phenotype of WD.

PMID- 16283885
TI  - An optimized DHPLC protocol for molecular testing of the EXT1 and EXT2 genes in
      hereditary multiple osteochondromas.
AB  - Hereditary multiple osteochondromas (MO) is an autosomal dominant bone disorder
      characterized by the presence of bony outgrowths (osteochondromas or exostoses)
      on the long bones. MO is caused by mutations in the EXT1 or EXT2 genes, which
      encode glycosyltransferases implicated in heparan sulfate biosynthesis. Standard
      mutation analysis performed by sequencing analysis of all coding exons of the
      EXT1 and EXT2 genes reveals a mutation in approximately 80% of the MO patients.
      We have now optimized and validated a denaturing high-performance liquid
      chromatography (DHPLC)-based protocol for screening of all EXT1- and EXT2-coding
      exons in a set of 49 MO patients with an EXT1 or EXT2 mutation. Under the
      optimized DHPLC conditions, all mutations were detected. These include 20
      previously described mutations and 29 new mutations - 20 new EXT1 and nine new
      EXT2 mutations. The protocol described here, therefore, provides a sensitive and
      cost-sparing alternative for direct sequencing analysis of the MO-causing genes.

PMID- 16283886
TI  - COMMD1 (MURR1) as a candidate in patients with copper storage disease of
      undefined etiology.

PMID- 16283887
TI  - Mild cystic fibrosis revealed by persistent hyponatremia during the French 2003
      heat wave, associated with the S1455X C-terminus CFTR mutation.

PMID- 16283888
TI  - GJB2 gene mutations in Slovak hearing-impaired patients of Caucasian origin:
      spectrum, frequencies and SNP analysis.

PMID- 16283889
TI  - Tetra-amelia and lung aplasia syndrome: report of a new family and exclusion of
      candidate genes.

PMID- 16283890
TI  - Identification of a novel TGFBR2 gene mutation in a Korean patient with Loeys
      Dietz aortic aneurysm syndrome; no mutation in TGFBR2 gene in 30 patients with
      classic Marfan's syndrome.

PMID- 16283891
TI  - Bilateral anophthalmia and brain malformations caused by a 20-bp deletion in the
      SOX2 gene.

PMID- 16283892
TI  - Severe autosomal dominant upper-limb mesomelic dysplasia: report of a second
      family.

PMID- 16283894
TI  - Making connections: healthcare as a case study in the social organisation of
      work.

PMID- 16283895
TI  - The promotion of private health insurance and its implications for the social
      organisation of healthcare: a case study of private sector obstetric practice in
      Chile.
AB  - This paper examines some of the implications of the process of privatisation of a
      national healthcare system for the delivery, organisation and, ultimately, the
      outcome of services. Through a case study of obstetric care in Chile, we
      illuminate the relationships between the macro-level of political decisions, the
      meso-level of the organisations through which government reforms were enacted,
      and the micro-level of clinical practice. We show that, for a significant
      proportion of Chilean women seeking maternity care, privatisation has led to
      expanded access and to ostensibly highly-personalised relationships with
      specialists. However, because of the fragmentation of maternity services, the
      altered work patterns for obstetricians occasioned by changes in healthcare
      financing and the relatively weak market position of most obstetricians, this
      personalised care is dependent on highly technologised obstetric practices. By
      examining the specific organisational arrangements under which private maternity
      care is conducted in Chile we shed light on the connection between privately
      funded maternity care and high caesarean section rates in this setting.

PMID- 16283896
TI  - Understanding the social organisation of maternity care systems: midwifery as a
      touchstone.
AB  - Theories of professions and healthcare organisation have difficulty in explaining
      variation in the organisation of maternity services across developed welfare
      states. Four countries - the United Kingdom, Finland, the Netherlands and Canada 
      serve as our case examples. While sharing several features, including political
      and economic systems, publicly-funded universal healthcare and favourable health
      outcomes, these countries nevertheless have distinct maternity care systems. We
      use the profession of midwifery, found in all four countries, as a 'touchstone'
      for exploring the sources of this diversity. Our analysis focuses on three key
      dimensions: (1) welfare state approaches to legalising midwifery and negotiating
      the role of the midwife in the division of labour; (2) professional boundaries in
      the maternity care domain; and (3) consumer mobilisation in support of midwifery
      and around maternity issues.

PMID- 16283897
TI  - Managerialism in the Australian public health sector: towards the hyper
      rationalisation of professional bureaucracies.
AB  - This paper draws on qualitative case-study research to discuss the impact of
      managerialism on the work organisation of public sector health professionals in
      Australia. The case studies included 71 semi-structured interviews with a broad
      range of public sector health professionals (predominantly nursing and allied
      health professionals, with some doctors and managers). The data are used to
      examine the implications of managerialism for the organisation of professional
      (public) bureaucracies. The findings show that while health professionals were
      able to exert their agency to influence managerial processes, the incorporation
      of managerial strategies into professional practice placed constraints upon
      professional autonomy. The impact of managerialism on professional bureaucracies
      is examined using the neo-Weberian framework of hyper-rationality, an ideal type
      derived from a combination of four forms of rationality identified in Weber's
      work: practical, formal, substantive and theoretical rationality. Applied to the
      social organisation of health-care work, this paper critically examines the
      utility of the hyper-rationality ideal type, noting its limitations and the
      insights it provides in conceptualising the impact of managerialism on
      professional (public) bureaucracies.

PMID- 16283898
TI  - What's in a care pathway? Towards a cultural cartography of the new NHS.
AB  - Maps are increasingly understood as socio-cultural and political constructs,
      rather than mirrors of nature. Drawing on the insights of cultural cartographers,
      this paper presents a critical analysis of a specific instance of map-making in
      health policy, namely the growing use of care pathways in care planning and
      service delivery. Widely regarded to date as devices for ensuring quality of
      care, equity of treatment, optimal resource allocation and a rational division of
      labour between healthcare professionals, they have been seen as helpful--and
      technically neutral--tools for routing patients through the system. By contrast,
      we argue that the metaphors are misleading: lived experience and its
      objectification in pathway maps continually re-create one another, as we explore
      the slippage between map, map-making and mapping. This paper is based on
      interviews and observations with a variety of healthcare workers in three areas
      of south eastern England. We trace the development of a series of pathways-in
      process, and show how they configure the patient, highlighting some aspects of
      their experiences, whilst silencing others. We also analyse the role of pathways
      in the carving up and surveillance of space round the emergence of the 'hybrid
      professional', particularly new practitioners such as GP specialists, specialist
      nurses, extended scope therapists and others. In considering the wider
      implications of care pathways as part of the contemporary discourse on policy,
      the paper critiques the rationalist, and sometimes evangelical assumptions
      underpinning their current popularity. In particular, we suggest that a critical
      and processual understanding of pathways might contribute to a more informed
      appreciation of their potential (and their limitations) as mechanisms for
      healthcare policy implementation.

PMID- 16283899
TI  - Arguing about the evidence: readers, writers and inscription devices in coronary
      heart disease risk assessment.
AB  - This paper examines the history of tools developed to assess an individual's risk
      of coronary heart disease. A close reading of the tools themselves is combined
      with an analysis of debates published in medical journals such as the British
      Medical Journal (BMJ) and The Lancet. These literary conversations between
      scientists and doctors reveal complex negotiations about the form and meaning of
      medical technologies that have yet to become fully 'stable'. Early tools were
      promoted as a response to the high cost of cholesterol-lowering drugs (statins),
      but came to embody broader attempts to shape medical practice. These include the
      promotion of what has been understood as evidence-based medicine and regulation
      by political and professional actors, as well as the spread of 'risk thinking'
      more generally. Despite having a central place in recent British guidelines and
      policy, there is a surprising variety of tools in circulation, and ongoing
      uncertainty about their use and value.

PMID- 16283900
TI  - Telephone triage, expert systems and clinical expertise.
AB  - This paper reports on a qualitative study of the use of an expert system
      developed for the British telephone triage service NHS Direct. This system, known
      as CAS, is designed to standardise and control the interaction between NHS Direct
      nurses and callers. The paper shows, however, that in practice the nurses use CAS
      in a range of ways and, in so doing, privilege their own expertise and deliver an
      individualised service. The paper concludes by arguing that NHS Direct
      management's policy of using CAS as a means of standardising service delivery
      will achieve only limited success due not only to the professional ideology of
      nursing but also to the fact that rule-based expert systems capture only part of
      what 'experts' do.

PMID- 16283901
TI  - Finding dignity in dirty work: the constraints and rewards of low-wage home care
      labour.
AB  - The ageing of the population in the US and elsewhere raises important questions
      about who will provide long-term care for elderly and disabled people. Current
      projections indicate that home care workers--most of whom are unskilled,
      untrained and underpaid--will increasingly absorb responsibility for care. While
      research to date confirms the demanding aspects of the work and the need for
      improved working conditions, little is known about how home care workers
      themselves experience and negotiate their labour on a daily basis. This paper
      attempts to address this gap by examining how home care workers assign meaning to
      their 'dirty work'. Qualitative interviews suggest that home care workers have a
      conflicted, often contradictory, relationship to their labour. Workers identify
      constraints that compromise their ability to do a good job or to experience their
      work as meaningful, but they also report several rewards that come from caring
      for dependent adults. I suggest workers draw dignity from these rewards,
      especially workers who enter home care after fleeing an alienating service job,
      within or outside the healthcare industry.

PMID- 16283902
TI  - Access, boundaries and their effects: legitimate participation in anaesthesia.
AB  - The distribution of work, knowledge and responsibilities in the delivery of
      anaesthesia has attained particular significance recently as attempts to meet the
      demands of the European Working Times Directive intensify existing pressures to
      reorganise anaesthetic services. Using Lave and Wenger's (1991) notions of
      'legitimate peripheral participation' in 'communities of practice' (and Wenger
      1998) to analyse ethnographic data of anaesthetic practice we illustrate how work
      and knowledge are currently configured, and when knowledge may legitimately be
      taken as the basis for action. The ability to initiate action, to prescribe
      healthcare interventions, we suggest, is a critical element in the organisation
      of anaesthetic practices and therefore central to any attempts to reshape the
      delivery of anaesthetic services.

PMID- 16283903
TI  - Skin-sensitizing and irritant properties of propylene glycol.
AB  - In the several publications reviewed in this article, propylene glycol (PG; 1,2
      propylene glycol) is described as a very weak contact sensitizer, if at all.
      However, particular exposures to PG-containing products might be associated with
      an elevated risk of sensitization. To identify such exposures, we analysed patch
      test data of 45 138 patients who have been tested with 20% PG in water between
      1992 and 2002. Out of these, 1044 patients (2.3%) tested positively, 1083 showed
      a doubtful, follicular or erythematous reaction (2.4%) and 271 explicit irritant
      reactions (0.6%). This profile of patch test reactions is indicative of a
      slightly irritant preparation, and thus, many of the 'weak positive' reactions
      must probably be interpreted as false positive. No private or occupational
      exposures associated with an increased risk of PG sensitization were identified,
      except for lower leg dermatitis. Therefore, according to our patch test data, PG
      seems to exhibit very low sensitization potential, and the risk for sensitization
      to PG on uncompromised skin seems to be very low.

PMID- 16283904
TI  - Predictive identification of human skin sensitization thresholds.
AB  - For years, methods have been available for the predictive identification of
      chemicals that possess the intrinsic potential to cause skin sensitization.
      However, many have proven less suitable for the determination of relative
      sensitizing potency. In this respect, the local lymph node assay (LLNA) has been
      shown to have a number of important advantages. Through interpolation of LLNA
      dose-response data, the concentration of a chemical required to produce a
      threshold positive response (a 3-fold increase in activity compared with
      concurrent vehicle controls, the EC3 value) can be measured. The robustness of
      this parameter has been demonstrated rigorously in terms of inter- and
      intralaboratory reproducibility. Additionally, the relationship between potency
      estimates from the LLNA and an appreciation of human potency based on clinical
      experience has been reported previously. In the present investigations, we have
      sought to consolidate further our understanding of the association between EC3
      values and human skin-sensitization potency by undertaking a thorough and
      extensive analysis of existing human predictive assays, particularly where dose
      response information is available, from historical human repeated insult patch
      tests (HRIPTs). From these human data, information on the approximate threshold
      for the induction of skin sensitization in the HRIPT was determined for 26 skin
      sensitizing chemicals. These data were then compared with LLNA-derived EC3
      values. The results from each assay, expressed as dose per unit area
      (microg/cm(2)), revealed a clear linear relationship between the 2 values,
      thereby substantiating further the utility of LLNA EC3 values for prediction of
      the relative human sensitizing potency of newly identified skin sensitizers.

PMID- 16283906
TI  - Long-term repetitive sodium lauryl sulfate-induced irritation of the skin: an in
      vivo study.
AB  - Skin may adapt to topical irritants through accommodation. This study focuses on
      long-term exposure to irritants and attempts to demonstrate accommodation. Sodium
      lauryl sulfate (SLS) induced irritant contact dermatitis at 3 concentrations
      (0.025% to 0.075%). Distilled water, acetone and an empty chamber served as
      controls. Experimental compounds were applied to forearms of 7 healthy volunteers
      for 24 hr before replacing by a fresh chamber for 6 non-consecutive weeks over
      103 days. Possible accommodation was quantified by visual scoring (erythema and
      dryness) and by bioengineering parameters: transepidermal water loss (TEWL),
      capacitance, chromametry and laser Doppler flowmetry (LDF). Significant erythema,
      dryness, elevated TEWL, skin colour reflectance and LDF values occurred during
      the exposure periods. Upon repeat exposure, an immediate and augmented response
      in erythema, TEWL, skin colour reflectance and LDF developed. However, irritant
      skin changes were not sustained. Irritation parameters return to baseline after
      cessation of exposure. There was no evidence of sustained irritation or
      accommodation after the last exposure. Study findings do not document sustained
      accommodation or adaptive hyposensitivity after long-term repetitive irritant
      exposure under these test conditions. Alternative models should be developed to
      prove or disprove the accommodation hypothesis.

PMID- 16283905
TI  - Experimental elicitation of contact allergy from a diazolidinyl urea-preserved
      cream in relation to anatomical region, exposure time and concentration.
AB  - The elicitation potential of the cosmetic preservative diazolidinyl urea was
      studied in formaldehyde- and diazolidinyl urea-sensitized volunteer patients
      using a stepwise controlled exposure design. The test product was a facial
      moisturizer, preserved with varying concentrations of diazolidinyl urea, ranging
      from 0.05% to 0.6%. A repeated open application-like exposure test was performed
      on volunteers and a control group with the test product containing increasing
      preservative concentrations, on arm, neck and face, sequentially, for 2 weeks or
      until dermatitis developed. The preservative action in the cream at different
      test concentrations was tested in microbial challenge tests and was found
      effective at all concentrations tested. The study established a non-eliciting
      concentration of diazolidinyl urea of 0.05% in formaldehyde-sensitive patients
      and showed that the skin reactivity depends on the anatomical region, increasing
      from the upper arm to neck and, possibly, to the face. The study design,
      beginning on the upper arm and moving on to the neck and face seems to be
      relevant for the study of reactions to cosmetic products. A clear dose-response
      relationship was seen regarding preservative concentration in the product.

PMID- 16283907
TI  - Colophonium and Compositae mix as markers of fragrance allergy: cross-reactivity
      between fragrance terpenes, colophonium and compositae plant extracts.
AB  - The aim of this study was to assess the strength of any association between
      sensitization to 'new' fragrance compounds and sensitization to Compositae,
      fragrance mix, Myroxylon pereirae resin and colophonium, respectively.
      Consecutive eczema patients were tested with a series of essential oils and
      selected fragrance compounds and another series of oxidized terpenes in
      connection with European multicentre fragrance projects. Contact allergy to
      either series was frequently detected, in 5% of 318 and 4.6% of 262 persons
      tested, and both had a statistically significant association with Compositae,
      colophonium and fragrance mix sensitization. The individual results indicated
      that simultaneously occurring positive reactions to essential oils, colophonium
      and Compositae were based on cross-reactivity rather than concomitant
      sensitization. Thus, all patients with positive reaction to the rare fragrance
      sensitizer beta-caryophyllene had positive colophonium reactions, and cross
      reactivity between essential oils and Compositae was related to the Compositae
      plant extracts of the Compositae mix and not the pure sesquiterpene lactones of
      the standard series. The implication is that Compositae mix and colophonium may
      be markers of fragrance allergy, which is important to know when assessing the
      relevance of positive reactions to Compositae plant extracts and colophonium.

PMID- 16283908
TI  - The development and course of patch-test reactions to 2-hydroxyethyl methacrylate
      and ethyleneglycol dimethacrylate.
AB  - Because Methacrylic monomers are used in dental work, dental personnel,
      technicians, and patients are at risk of being sensitized. 2-hydroxyethyl
      methacrylate (2-HEMA) and ethyleneglycol dimethacrylate (EGDMA) are commonly
      used. Allergic test reactions to them sometimes appear beyond D7. This study was
      designed to study the development and course of positive test reactions to 2-HEMA
      and EGDMA in allergic patients as a mean to elucidate the issue of patch-test
      sensitization. 12 patients with contact allergy to 2-HEMA and EGDMA were retested
      with dilution series. The clinical course was followed for 1 month. During the
      study, 25 positive test reactions to 2-HEMA and 19 to EGDMA were diagnosed.
      Within the 1st week, 21 were noted for 2-HEMA and 18 for EGDMA. After 10 days,
      another 2 reactions appeared for 2-HEMA and 1 for EGDMA. All but 1 patient with
      the latter reactions also had positive reactions within the 1st week. After 1
      month, 12 reactions for 2-HEMA and 10 for EGDMA remained. Patch-test reactions to
      2-HEMA and EGDMA are long-lasting. The patch-test concentrations of 2.0% for 2
      HEMA and EGDMA may be continually used. Positive test reactions emerging after 10
      days do not automatically imply active sensitization.

PMID- 16283909
TI  - Phenylephrine and acute periorbital dermatitis.

PMID- 16283910
TI  - Fixed drug eruption caused by ornidazole.

PMID- 16283911
TI  - Contact allergy to aluminium in patients hyposensitized with aluminium-containing
      hyposensitizing extracts.

PMID- 16283912
TI  - Allergic contact dermatitis to naftifine.

PMID- 16283913
TI  - Delayed-type hypersensitivity dermatitis to ethylene oxide.

PMID- 16283914
TI  - Evaluation of the epidemiological importance of classical swine fever infected,
      E2 sub-unit marker vaccinated animals with RT-nPCR positive blood samples.
AB  - It has been demonstrated that pigs that have been double vaccinated with an E2
      sub-unit marker vaccine and that are infected with classical swine fever virus
      (CSFV) through a natural contact infection may react positive in a CSFV detecting
      RT-nPCR test, whereas no virus could be isolated by using the conventional virus
      isolation (VI) technique. To evaluate whether these vaccinated and infected pigs
      may spread the virus, three experiments were set up. In the first, susceptible
      pigs were inoculated with serum originating from vaccinated RT-nPCR positive
      pigs. In the second, vaccinated RT-nPCR positive pigs were brought into contact
      with sentinel animals. In the third, vertical transmission was evaluated in RT
      nPCR positive vaccinated pregnant gilts. In the first two experiments, no proof
      of virus transmission was found, whereas in the third vertical transmission was
      observed. The conclusion is that in vaccinated pigs that are positive in RT-nPCR
      but negative in VI, the level of circulating virus is probably not high enough
      for horizontal transmission, whereas vertical transmission of the virus is
      possible.

PMID- 16283915
TI  - VP2-segment sequence analysis of some isolates of bluetongue virus recovered in
      the Mediterranean basin during the 1998-2003 outbreak.
AB  - The complete nucleotide sequences of the VP2 segments of bluetongue virus (BTV)
      isolates recovered from Italy, Greece and Israel, from 1998 to 2003, were
      determined. Phylogenetic analysis of these sequences, those from related viruses
      and the South African vaccine strains, were used to determine the probable
      geographic origin of BTV incursions into Italy. Results indicated that viruses
      from each of the four serotypes isolated in Italy (2, 4, 9 and 16) possibly had a
      different origin. Analysis of the bluetongue virus serotype 2 (BTV-2) isolates
      gave evidence that this serotype probably moved from Tunisia. BTV-4 results
      showed probable incursion from the southwest and not from Greece or Israel. BTV-9
      isolates clearly have an eastern origin (most probably Greece), whereas BTV-16
      isolates are indistinguishable from the BTV-16 live attenuated vaccine strain.
      The phylogenetic findings were supported by polyacrylamide gel electrophoresis
      (PAGE) analysis of the complete amplified genome of each isolate except for BTV
      16 Italian field isolate, which showed a slightly different PAGE profile. A
      combination of the complete VP2 sequencing and PAGE analysis of complete genomes,
      allowed not only phylogenetic analysis, but also vaccine detection and assessment
      of reassortment events.

PMID- 16283916
TI  - Changes in peripheral blood leucocyte counts and subpopulations after
      experimental infection with BVDV and/or Mannheimia haemolytica.
AB  - Leucocyte counts and subpopulations were studied in peripheral blood from calves
      experimentally infected in the respiratory tract with either bovine virus
      diarrhoea virus (BVDV) or Mannheimia haemolytica (Mh), or with a combination of
      both agents (BVDV/Mh). A non-inoculated control group was included. Peripheral
      blood samples were obtained for total leucocyte counts, and for neutrophil,
      lymphocyte and monocyte counts. The numbers of blood lymphocytes expressing the
      surface antigens CD4, CD8, WC1, B and IL-2R were analysed using flow cytometry.
      The results showed that BVDV inoculation induced a significant decrease in total
      leucocyte counts and in neutrophil and lymphocyte numbers, while Mh inoculation
      induced significant increases in total leucocyte counts and neutrophils, while
      the lymphocyte count decreased. In the BVDV/Mh group, the total leucocyte count
      and the lymphocyte numbers decreased significantly. In this group, the lymphocyte
      numbers remained on a very low level throughout the rest of the study. The
      numbers of CD4+, CD8+ and WC1+ lymphocytes decreased significantly compared with
      before inoculations mainly in the BVDV and BVDV/Mh groups. The drops were most
      pronounced in the BVDV/Mh group. The numbers of B+ lymphocytes and IL-2R+ cells
      did not change significantly.

PMID- 16283918
TI  - Adherence of Streptococcus suis to porcine endothelial cells.
AB  - Streptococcus suis can cause invasive diseases in pigs and humans, such as
      meningitis or arthritis. Adherence to and invasion of endothelial cells might
      represent important steps in survival and spread of S. suis within the host. We
      tested in vitro adherence and invasion of S. suis strains using a porcine brain
      microvascular and aortal endothelial cell line. Four S. suis strains were tested
      with and without prior treatment with porcine serum containing anti-S. suis
      antibodies. Strains included a capsular serotype 2 strain and its non
      encapsulated isogenic mutant strain, as well as two non-typeable (NT) strains,
      which expressed no capsule under our experimental conditions. Strains adhered to
      both cell lines to different extents depending on encapsulation and pre-treatment
      with porcine immune serum. The serotype 2 strain showed almost no adherence,
      whereas the non-encapsulated mutant strain adhered strongly. Similarly, both NT
      strains adhered substantially better than the serotype 2 strain. Pre-treatment of
      bacteria with porcine serum increased adherence of the encapsulated serotype 2
      strain and decreased adherence of the non-encapsulated strains. None of the
      strains was able to efficiently invade either of the two cell lines, except for
      one NT strain, which showed a very low extend of invasion. Our results suggest
      that S. suis can adhere to but not invade porcine endothelial cells, and that
      this interaction may involve different bacterial surface structures, such as
      capsular polysaccharides and/or binding sites for serum components.

PMID- 16283917
TI  - The prevalences of Brachyspira spp. and Lawsonia intracellularis in Swedish
      piglet producing herds and wild boar population.
AB  - The aim of the present study was to survey the prevalences of the enteric
      pathogens Brachyspira hyodysenteriae, Brachyspira pilosicoli and Lawsonia
      intracellularis in Swedish growing pigs and in the Swedish wild boar population
      and to relate these findings to clinical signs. The study included 105 randomly
      selected herds, constituting approximately one third of Swedish herds with a herd
      size of >100 sows. The herds were located all over the country. In these herds,
      growth promoters were not used and pigs sampled were not subjected to any
      medication. From each herd, samples were taken from 10 growing pigs aged 8-12
      weeks, corresponding to approximately 2.5% of all growing pigs present in the
      herd at the sampling occasion. If possible, the samples were taken from pigs with
      diarrhoea. Forty-eight faecal samples and 71 rectal swabs were also taken from
      free-living wild boars (31 piglets, 19 growers and 21 adult animals) at shooting.
      The samples were analysed by culture and biochemical tests for the presence of
      Brachyspira spp. and by nested PCR for the presence of L. intracellularis.
      Brachyspira hyodysenteriae was not demonstrated in any sample. Brachyspira
      intermedia was detected in 22 samples originating from 15 herds, Brachyspira
      innocens/Brachyspira murdochii was detected in 370 samples from 82 herds and B.
      pilosicoli was detected in 134 samples originating from 34 herds. In 21 herds and
      in 534 samples, no Brachyspira spp. were detected. Lawsonia intracellularis was
      demonstrated in 285 samples from 50 herds. Further, 418 samples from conventional
      herds were negative with respect to L. intracellularis and in 345 samples the PCR
      had been inhibited. All samples from the wild boars were negative for Brachyspira
      spp., 12 of 48 samples were negative for L. intracellularis, and in 36 wild boar
      samples, the PCR was inhibited.

PMID- 16283919
TI  - Characterization of antibiotic resistance genes and virulence factors in faecal
      enterococci of wild animals in Portugal.
AB  - Antibiotic susceptibility was tested in 140 non-selected enterococci (73
      Enterococcus faecalis, 45 E. faecium and 22 of other species) recovered from
      faecal samples of 77 wild animals in Portugal. Susceptibility testing for 11
      antibiotics (vancomycin, teicoplanin, ampicillin, streptomycin, gentamicin,
      kanamycin, chloramphenicol, tetracycline, erythromycin, quinupristin-dalfopristin
      and ciprofloxacin) was determined by disk diffusion and agar dilution methods.
      Forty-four isolates (31.4%) showed susceptibility to all the antibiotics tested
      (5.5% of E. faecalis; 62.2% of E. faecium; and 78.6% of E. hirae). Neither
      ampicillin-resistance nor acquired-vancomycin-resistance was detected and 1.4% of
      the isolates showed high-level-resistance for gentamicin or streptomycin.
      Tetracycline and erythromycin resistances were shown in 28.6% and 20.1% of the
      isolates, respectively. Antibiotic resistance genes were studied by polymerase
      chain reaction (PCR) and sequencing and tet(M) + tet(L), erm(B) or aac(6')
      aph(2'') genes were detected in most of tetracycline-, erythromycin- or
      gentamicin-resistant enterococci respectively. Genes encoding virulence factors
      were studied by PCR and a wide variety of virulence genes were detected in most
      of E. faecalis isolates but were rarely found in E. faecium and not detected in
      the other species. The prevalence of genes encoding virulence factors in E.
      faecalis was as follows: cpd (98.6%), gelE (75.3%), agg (30.1%), fsr (17.8%), ace
      (9.6%) and esp (4.1%). Low percentages of antibiotic resistance was found in the
      faecal enterococci of wild animals but a wide variety of virulence genes were
      detected among E. faecalis isolates although were rare in the other species.

PMID- 16283921
TI  - Detection of canine distemper virus in blood samples by reverse transcription
      loop-mediated isothermal amplification.
AB  - Reverse transcription loop-mediated isothermal amplification (RT-LAMP) was used
      to detect canine distemper virus (CDV) genomic RNA. A set of four primers, two
      outer and two inner, were designed from CDV genomic RNA targeting the
      nucleocapsid protein gene. The optimal reaction time and temperature for LAMP
      were determined to be 60 min at 65 degrees C. The relative sensitivity and
      specificity of RT-LAMP was found to be 100% and 93.3%, respectively, based on 50
      canine blood samples and using RT-PCR as the gold standard. The detection limit
      of the RT-LAMP method was 100 times lower than with RT-PCR (10-1TCID50 ml(-1)
      versus 10TCID50 ml(-1)). In addition to the advantage resulting from the visual
      detection of the end-product, the LAMP method is fast, requiring only 1 h to
      complete the assay. The LAMP method is a viable alternative to RT-PCR for
      diagnosing CDV infection in dogs. The LAMP method might be useful as an on site
      diagnostic assay for detecting CDV.

PMID- 16283920
TI  - The persistence of Brucella melitensis in experimentally infected ewes through
      three reproductive cycles.
AB  - The authors studied the persistence of infection in 46 ewes experimentally
      infected with Brucella melitensis biovar 3 and monitored through three subsequent
      reproductive cycles. The entire experimental period lasted for 151 weeks.
      Infection of ewes and elimination of Brucella in milk, or its presence in vaginal
      discharges, persisted throughout the duration of the trial, as demonstrated by
      recurrent elimination of Brucella in milk and vaginal discharges. Brucella
      melitensis was recovered from the tissues of one ewe killed at the end of the
      trial. The strain was recovered from vaginal swabs and milk following parturition
      in the third reproductive cycle from an ewe that had aborted in the first cycle
      but was not pregnant in the second cycle. From a public health point of view, the
      periodical recovery of Brucella from the milk during the entire trial period
      illustrated that brucellosis in sheep remains a continuous occupational risk and
      a significant public health problem for consumers of fresh milk and milk
      products. That risk may persist for at least 3 years following the initial
      infection of the flock. Lamb antibody titres became negative in all lambs within
      5 months after birth. This suggested that serological tests on lambs may have no
      practical diagnostic significance if performed during the first 5 months of life.
      Nevertheless, the birth of three infected lambs suggested that the phenomenon of
      latent carrier state may represent another way for B. melitensis to persist in a
      flock.

PMID- 16283922
TI  - Prevalence of fasciolosis in Zambian cattle observed at selected abattoirs with
      emphasis on age, sex and origin.
AB  - The aim of this study was to determine the prevalence and some factors
      influencing occurrence of fasciolosis in cattle, carried out at selected major
      abattoirs in Zambia. Of 841 cattle livers inspected and 677 faecal samples
      analysed, prevalence rates of 53.9% and 48.9%, respectively, were found.
      Cumulative prevalence of 60.9% (n = 677) was recorded. According to age, no
      significant difference of infection was found. Female cattle on liver inspection
      (59.3%) and coprological examination (65.2%) had significantly higher (P < 0.001)
      rates than males (44.5% and 36.3% respectively). Origin of cattle had a
      significant influence (P < 0.001) on the prevalence rate. According to fluke egg
      count classification, 68.5% of cattle had light infection, 20.9% moderate, 4.4%
      heavy and 6.2% severe. These results indicate that Fasciola gigantica infection
      is an important condition that leads to high liver condemnations and/or trimmings
      in cattle tendered for slaughter.

PMID- 16283923
TI  - Commensurate distances and similar motifs in genetic congruence and protein
      interaction networks in yeast.
AB  - BACKGROUND: In a genetic interaction, the phenotype of a double mutant differs
      from the combined phenotypes of the underlying single mutants. When the single
      mutants have no growth defect, but the double mutant is lethal or exhibits slow
      growth, the interaction is termed synthetic lethality or synthetic fitness. These
      genetic interactions reveal gene redundancy and compensating pathways. Recently
      available large-scale data sets of genetic interactions and protein interactions
      in Saccharomyces cerevisiae provide a unique opportunity to elucidate the
      topological structure of biological pathways and how genes function in these
      pathways. RESULTS: We have defined congruent genes as pairs of genes with similar
      sets of genetic interaction partners and constructed a genetic congruence network
      by linking congruent genes. By comparing path lengths in three types of networks
      (genetic interaction, genetic congruence, and protein interaction), we discovered
      that high genetic congruence not only exhibits correlation with direct protein
      interaction linkage but also exhibits commensurate distance with the protein
      interaction network. However, consistent distances were not observed between
      genetic and protein interaction networks. We also demonstrated that congruence
      and protein networks are enriched with motifs that indicate network transitivity,
      while the genetic network has both transitive (triangle) and intransitive
      (square) types of motifs. These results suggest that robustness of yeast cells to
      gene deletions is due in part to two complementary pathways (square motif) or
      three complementary pathways, any two of which are required for viability
      (triangle motif). CONCLUSION: Genetic congruence is superior to genetic
      interaction in prediction of protein interactions and function associations.
      Genetically interacting pairs usually belong to parallel compensatory pathways,
      which can generate transitive motifs (any two of three pathways needed) or
      intransitive motifs (either of two pathways needed).

PMID- 16283924
TI  - The yeast kinome displays scale free topology with functional hub clusters.
AB  - BACKGROUND: The availability of interaction databases provides an opportunity for
      researchers to utilize immense amounts of data exclusively in silico. Recently
      there has been an emphasis on studying the global properties of biological
      interactions using network analysis. While this type of analysis offers a wide
      variety of global insights it has surprisingly not been used to examine more
      localized interactions based on mechanism. In as such we have particular interest
      in the role of key topological components in signal transduction cascades as they
      are vital regulators of healthy and diseased cell states. RESULTS: We have used
      publicly available databases and a novel software tool termed Hubview to model
      the interactions of a subset of the yeast interactome, specifically protein
      kinases and their interaction partners. Analysis of the connectivity distribution
      has inferred a fat-tailed degree distribution with parameters consistent with
      those found in other biological networks. In addition, Hubview identified a
      functional clustering of a large group of kinases, distributed between three
      separate groupings. The complexity and average degree for each of these clusters
      is indicative of a specialized function (cell cycle propagation, DNA repair and
      pheromone response) and relative age for each cluster. CONCLUSION: Using
      connectivity analysis on a functional subset of proteins we have evidence that
      reinforces the scale free topology as a model for protein network evolution. We
      have identified the hub components of the kinase network and observed a tendency
      for these kinases to cluster together on a functional basis. As such, these
      results suggest an inherent trend to preserve scale free characteristics at a
      domain based modular level within large evolvable networks.

PMID- 16283925
TI  - Bright light treatment of depression for older adults [ISRCTN55452501].
AB  - BACKGROUND: The incidence of insomnia and depression in the elder population is
      significant. It is hoped that use of light treatment for this group could provide
      safe, economic, and effective rapid recovery. METHODS: In this home-based trial
      we treated depressed elderly subjects with bright white (8,500 Lux) and dim red
      (<10 Lux) light for one hour a day at three different times (morning, mid-wake
      and evening). A placebo response washout was used for the first week. Wake
      treatment was conducted prior to the initiation of treatment, to explore
      antidepressant response and the interaction with light treatment. Urine and
      saliva samples were collected during a 24-hour period both before and after
      treatment and assayed for aMT6s and melatonin respectively to observe any change
      in circadian timing. Subjects wore a wrist monitor to record light exposure and
      wrist activity. Daily log sheets and weekly mood (GDS) and physical symptom
      (SAFTEE) scales were administered. Each subject was given a SCID interview and
      each completed a mood questionnaire (SIGH-SAD-SR) before and after treatment.
      Also, Hamilton Depression Rating (SIGH-SAD version) interviews were conducted by
      a researcher who was blind to the treatment condition. A control group of
      healthy, age-matched, volunteers was studied for one day to obtain baseline data
      for comparison of actigraphy and hormone levels. RESULTS: Eighty-one volunteers,
      between 60 and 79 years old, completed the study. Both treatment and placebo
      groups experienced mood improvement. Average GDS scores improved 5 points, the
      Hamilton Depression Rating Scale (HDRS) 17 scores (extracted from the self-rated
      SIGH-SAD-SR) improved 6 points. There were no significant treatment effects or
      time-by-treatment interactions. No significant adverse reactions were observed in
      either treatment group. The assays of urine and saliva showed no significant
      differences between the treatment and placebo groups. The healthy control group
      was active earlier and slept earlier but received less light than the depressed
      group at baseline. CONCLUSION: Antidepressant response to bright light treatment
      in this age group was not statistically superior to placebo. Both treatment and
      placebo groups experienced a clinically significant overall improvement of 16%.

PMID- 16283926
TI  - Bright green light treatment of depression for older adults [ISRCTN69400161].
AB  - BACKGROUND: Bright white light has been successfully used for the treatment of
      depression. There is interest in identifying which spectral colors of light are
      the most efficient in the treatment of depression. It is theorized that green
      light could decrease the intensity duration of exposure needed. Late Wake
      Treatment (LWT), sleep deprivation for the last half of one night, is associated
      with rapid mood improvement which has been sustained by light treatment. Because
      spectral responsiveness may differ by age, we examined whether green light would
      provide efficient antidepressant treatment in an elder age group. METHODS: We
      contrasted one hour of bright green light (1,200 Lux) and one hour of dim red
      light placebo (<10 Lux) in a randomized treatment trial with depressed elders.
      Participants were observed in their homes with mood scales, wrist actigraphy and
      light monitoring. On the day prior to beginning treatment, the participants self
      administered LWT. RESULTS: The protocol was completed by 33 subjects who were 59
      to 80 years old. Mood improved on average 23% for all subjects, but there were no
      significant statistical differences between treatment and placebo groups. There
      were negligible adverse reactions to the bright green light, which was well
      tolerated. CONCLUSION: Bright green light was not shown to have an antidepressant
      effect in the age group of this study, but a larger trial with brighter green
      light might be of value.

PMID- 16283927
TI  - Role of cultivation media in the development of yeast strains for large scale
      industrial use.
AB  - The composition of cultivation media in relation to strain development for
      industrial application is reviewed. Heterologous protein production and pentose
      utilization by Saccharomyces cerevisiae are used to illustrate the influence of
      media composition at different stages of strain construction and strain
      development. The effects of complex, defined and industrial media are compared.
      Auxotrophic strains and strain stability are discussed. Media for heterologous
      protein production and for bulk bio-commodity production are summarized.

PMID- 16283928
TI  - Large-scale genetic variation of the symbiosis-required megaplasmid pSymA
      revealed by comparative genomic analysis of Sinorhizobium meliloti natural
      strains.
AB  - BACKGROUND: Sinorhizobium meliloti is a soil bacterium that forms nitrogen-fixing
      nodules on the roots of leguminous plants such as alfalfa (Medicago sativa). This
      species occupies different ecological niches, being present as a free-living soil
      bacterium and as a symbiont of plant root nodules. The genome of the type strain
      Rm 1021 contains one chromosome and two megaplasmids for a total genome size of 6
      Mb. We applied comparative genomic hybridisation (CGH) on an oligonucleotide
      microarrays to estimate genetic variation at the genomic level in four natural
      strains, two isolated from Italian agricultural soil and two from desert soil in
      the Aral Sea region. RESULTS: From 4.6 to 5.7 percent of the genes showed a
      pattern of hybridisation concordant with deletion, nucleotide divergence or ORF
      duplication when compared to the type strain Rm 1021. A large number of these
      polymorphisms were confirmed by sequencing and Southern blot. A statistically
      significant fraction of these variable genes was found on the pSymA megaplasmid
      and grouped in clusters. These variable genes were found to be mainly
      transposases or genes with unknown function. CONCLUSION: The obtained results
      allow to conclude that the symbiosis-required megaplasmid pSymA can be considered
      the major hot-spot for intra-specific differentiation in S. meliloti.

PMID- 16283929
TI  - Cross-cultural validation and analysis of responsiveness of the QUALIOST: QUAlity
      of Life questionnaire In OSTeoporosis.
AB  - BACKGROUND: The QUALIOST was designed for use with the SF-36 to measure
      established osteoporosis-specific quality of life (QoL). The reliability
      (internal consistency and test-retest) and validity of the questionnaire were
      established in a stand-alone psychometric validation study. The objective of this
      paper is to provide additional information on the instrument's responsiveness
      using clinical trial data, along with the reliability and validity of translated
      versions. METHODS: The Spinal Osteoporosis Therapeutic Intervention (SOTI) was an
      international clinical trial comparing strontium ranelate to placebo on the
      occurrence of new vertebral fracture in patients with postmenopausal
      osteoporosis. QoL was a secondary endpoint, assessed using the SF-36 and QUALIOST
      at baseline and every six months, with the main analysis at 3-year follow-up.
      Questionnaire acceptability, analysis of the hypothesised structure, internal
      consistency reliability and responsiveness to clinical change over time were
      assessed at the 3-year follow up. RESULTS: 1592 patients from 11 countries
      completed at least one QoL questionnaire. The psychometric properties of the
      questionnaires were assessed on cross-sectional (N = 1486) and longitudinal (N =
      1288) data. Item discriminant validity of the QUALIOST was excellent, as was item
      convergent validity, with 100% of item-scale correlations being above the 0.40
      level. Internal consistency reliability was also extremely good, with high
      Cronbach's alpha scores above the 0.70 benchmark. Responsiveness results were
      consistent for all QUALIOST scores, indicating that greater decreases in QoL
      corresponded to greater numbers of fractures experienced. QUALIOST scores also
      differed according to the type of fracture suffered. This was demonstrated by
      increased effect sizes for more severe vertebral fractures (clinical vertebral
      and painful vertebral). In comparing responsiveness, the QUALIOST scores were
      generally more consistent than those of the SF-36. Most notably, the QUALIOST was
      more responsive with regard to painful vertebral fractures than the SF-36.
      CONCLUSION: The QUALIOST is a reliable and valid tool for measuring QoL in
      postmenopausal osteoporotic women. Being available in several validated language
      versions, it is ready to be used in a variety of settings, including
      international clinical trials.

PMID- 16283930
TI  - Cardiovascular disease, risk factors and heart rate variability in the elderly
      general population: design and objectives of the CARdiovascular disease, Living
      and Ageing in Halle (CARLA) Study.
AB  - BACKGROUND: The increasing burden of cardiovascular diseases (CVD) in the ageing
      population of industrialized nations requires an intensive search for means of
      reducing this epidemic. In order to improve prevention, detection, therapy and
      prognosis of cardiovascular diseases on the population level in Eastern Germany,
      it is necessary to examine reasons for the East-West gradient of CVD morbidity
      and mortality, potential causal mechanisms and prognostic factors in the elderly.
      Psychosocial and nutritional factors have previously been discussed as possible
      causes for the unexplained part of the East-West gradient. A reduced heart rate
      variability appears to be associated with cardiovascular disease as well as with
      psychosocial and other cardiovascular risk factors and decreases with age.
      Nevertheless, there is a lack of population-based data to examine the role of
      heart rate variability and its interaction with psychosocial and nutritional
      factors regarding the effect on cardiovascular disease in the ageing population.
      There also is a paucity of epidemiological data describing the health situation
      in Eastern Germany. Therefore, we conduct a population-based study to examine the
      distribution of CVD, heart rate variability and CVD risk factors and their
      associations in an elderly East German population. This paper describes the
      design and objectives of the CARLA Study. METHODS/DESIGN: For this study, a
      random sample of 45-80 year-old inhabitants of the city of Halle (Saale) in
      Eastern Germany was drawn from the population registry. By the end of the
      baseline examination (2002-2005), 1750 study participants will have been
      examined. A multi-step recruitment strategy aims at achieving a 70% response
      rate. Detailed information is collected on own and family medical history,
      socioeconomic, psychosocial, behavioural and biomedical factors. Medical
      examinations include anthropometric measures, blood pressure of arm and ankle, a
      10-second and a 20-minute electrocardiogram, a general physical examination, an
      echocardiogram, and laboratory analyses of venous blood samples. On 200
      participants, a 24-hour electrocardiogram is recorded. A detailed system of
      quality control ensures high data quality. A follow-up examination is planned.
      DISCUSSION: This study will help to elucidate pathways to CVD involving autonomic
      dysfunction and lifestyle factors which might be responsible for the CVD epidemic
      in some populations.

PMID- 16283931
TI  - Analysis of variation of amplitudes in cell cycle gene expression.
AB  - BACKGROUND: Variation in gene expression among cells in a population is often
      considered as noise produced from gene transcription and post-transcription
      processes and experimental artifacts. Most studies on noise in gene expression
      have emphasized a few well-characterized genes and proteins. We investigated
      whether different cell-arresting methods have impacts on the maximum expression
      levels (amplitudes) of a cell cycle related gene. RESULTS: By introducing random
      noise, modeled by a von Mises distribution, to the phase angle in a sinusoidal
      model in a cell population, we derived a relationship between amplitude and the
      distribution of noise in maximum transcription time (phase). We applied our
      analysis to Whitfield's HeLa cell cycle data. Our analysis suggests that among 47
      cell cycle related genes common to the 2nd experiment (thymidine-thymidine
      method) and the 4th experiment (thymidine-nocodazole method): (i) the amplitudes
      of CDC6 and PCNA, which are expressed during G1/S phase, are smaller in the 2nd
      experiment than in the 4th, while the amplitude of CDC20, which is expressed
      during G2/M phase, is smaller in the 4th experiment; and (ii) the two cell
      arresting methods had little impact on the amplitudes of the other 43 genes in
      the 2nd and 4th experiments. CONCLUSION: Our analysis suggests that procedures
      that arrest cells in different stages of the cell cycle differentially affect
      expression of some cell cycle related genes once the cells are released from
      arrest. The impact of the cell-arresting method on expression of a cell cycle
      related gene can be quantitatively estimated from the ratio of two estimated
      amplitudes in two experiments. The ratio can be used to gauge the variation in
      the phase/peak expression time distribution involved in stochastic transcription
      and post-transcriptional processes for the gene. Further investigations are
      needed using normal, unperturbed and synchronized HeLa cells as a reference to
      compare how many cell cycle related genes are directly and indirectly affected by
      various cell-arresting methods.

PMID- 16283933
TI  - Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in
      primary human alveolar and bronchial epithelial cells.
AB  - BACKGROUND: Fatal human respiratory disease associated with influenza A subtype
      H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and
      Cambodia. We previously demonstrated that patients with H5N1 disease had
      unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10).
      Furthermore, when compared with human influenza virus subtype H1N1, the H5N1
      viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro
      inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10)
      from primary human macrophages in vitro, which suggests that cytokines
      dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory
      epithelial cells are the primary target cell for replication of influenza
      viruses, it is pertinent to investigate the cytokine induction profile of H5N1
      viruses in these cells. METHODS: We used quantitative RT-PCR and ELISA to compare
      the profile of cytokine and chemokine gene expression induced by H5N1 viruses
      A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04)
      with that of human H1N1 virus in human primary alveolar and bronchial epithelial
      cells in vitro. RESULTS: We demonstrated that in comparison to human H1N1
      viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10,
      interferon beta, RANTES (regulated on activation, normal T cell expressed and
      secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial
      epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to
      be even more potent at inducing IP-10 than H5N1/97 virus. CONCLUSION: The H5N1/97
      and H5N1/04 subtype influenza A viruses are more potent inducers of
      proinflammatory cytokines and chemokines in primary human respiratory epithelial
      cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines
      may be relevant to the pathogenesis of human H5N1 disease.

PMID- 16283934
TI  - Neurophysiological correlates of mismatch in lexical access.
AB  - BACKGROUND: In the present study neurophysiological correlates related to
      mismatching information in lexical access were investigated with a fragment
      priming paradigm. Event-related brain potentials were recorded for written words
      following spoken word onsets that either matched (e.g., kan - Kante [Engl.
      edge]), partially mismatched (e.g., kan - Konto [Engl. account]), or were
      unrelated (e.g., kan - Zunge [Engl. tongue]). Previous psycholinguistic research
      postulated the activation of multiple words in the listeners' mental lexicon
      which compete for recognition. Accordingly, matching words were assumed to be
      strongly activated competitors, which inhibit less strongly activated partially
      mismatching words. RESULTS: ERPs for matching and unrelated control words
      differed between 300 and 400 ms. Difference waves (unrelated control words -
      matching words) replicate a left-hemispheric P350 effect in this time window.
      Although smaller than for matching words, a P350 effect and behavioural
      facilitation was also found for partially mismatching words. Minimum norm
      solutions point to a left hemispheric centro-temporal source of the P350 effect
      in both conditions. The P350 is interpreted as a neurophysiological index for the
      activation of matching words in the listeners' mental lexicon. In contrast to the
      P350 and the behavioural responses, a brain potential ranging between 350 and 500
      ms (N400) was found to be equally reduced for matching and partially mismatching
      words as compared to unrelated control words. This latter effect might be related
      to strategic mechanisms in the priming situation. CONCLUSION: A left-hemispheric
      neuronal network engaged in lexical access appears to be gradually activated by
      matching and partially mismatching words. Results suggest that neural processing
      of matching words does not inhibit processing of partially mismatching words
      during early stages of lexical identification. Furthermore, the present results
      indicate that neurophysiological correlates observed in fragment priming reflect
      different aspects of target processing that are cumulated in behavioural
      responses. Particularly the left-hemispheric P350 difference potential appears to
      be closely related to fine-grained activation differences of modality-independent
      representations in the listeners' mental lexicon. This neurophysiological index
      might guide future studies aimed at investigating neural aspects of lexical
      access.

PMID- 16283932
TI  - Neglected diseases of neglected populations: thinking to reshape the determinants
      of health in Latin America and the Caribbean.
AB  - BACKGROUND: People living in poverty throughout the developing world are heavily
      burdened with neglected communicable diseases and often marginalized by the
      health sector. These diseases are currently referred to as Neglected Diseases of
      Neglected Populations. The neglected diseases create social and financial burdens
      to the individual, the family, the community, and the nation. DISCUSSION:
      Numerous studies of successful individual interventions to manage communicable
      disease determinants in various types of communities have been published, but few
      have applied multiple interventions in an integrated, coordinated manner. We have
      identified a series of successful interventions and developed three hypothetical
      scenarios where such interventions could be applied in an integrated, multi
      disease, inter-programmatic, and/or inter-sectoral approach for prevention and
      control of neglected diseases in three different populations: a slum, an
      indigenous community, and a city with a mix of populations. SUMMARY: The
      objective of this paper is to identify new opportunities to address neglected
      diseases, improve community health and promote sustainable development in
      neglected populations by highlighting examples of key risk and protective factors
      for neglected diseases which can be managed and implemented through multi-disease
      based, integrated, inter-programmatic, and/or inter-sectoral approaches. Based on
      a literature review, analysis and development of scenarios we visualize how
      multiple interventions could manage multiple disease problems and propose these
      as possible strategies to be tested. We seek to stimulate intra- and inter
      sectoral dialogue which will help in the construction of new strategies for
      neglected diseases (particularly for the parasitic diseases) which could benefit
      the poor and marginalized based on the principle of sustainability and
      understanding of key determinants of health, and lead to the establishment of
      pilot projects and activities which can contribute to the achievement of the
      Millennium Development Goals.

PMID- 16283935
TI  - Measurement of the total antioxidant response using a novel automated method in
      subjects with nonalcoholic steatohepatitis.
AB  - BACKGROUND: Oxidative stress, an increase in oxidants and/or a decrease in
      antioxidant capacity, is one of the potential biochemical mechanisms involved in
      the pathogenesis of nonalcoholic steatohepatitis. We aimed to investigate the
      total antioxidant response using a novel automated method in nonalcoholic
      steatohepatitis subjects. As a reciprocal measure, we also aimed to determine
      total peroxide level in the same plasma samples. METHODS: Twenty-two subjects
      with biopsy proven nonalcoholic steatohepatitis and 22 healthy controls were
      enrolled. Total antioxidant response and total peroxide level measurements were
      done in all participants. The ratio percentage of total peroxide level to total
      antioxidant response was regarded as oxidative stress index. RESULTS: Total
      antioxidant response of subjects with nonalcoholic steatohepatitis was
      significantly lower than controls (p < 0.05), while mean total peroxide level and
      mean oxidative stress index were higher (all p < 0.05). In subjects with
      nonalcoholic steatohepatitis, fibrosis score was significantly correlated with
      total peroxide level, total antioxidant response and oxidative stress index (p <
      0.05, r = 0.607; p < 0.05, r = -0.506; p < 0.05, r = 0.728, respectively).
      However, no correlation was observed between necroimflamatory grade and those
      oxidative status parameters (all p > 0.05). CONCLUSION: Nonalcoholic
      steatohepatitis is associated with increased oxidant capacity, especially in the
      presence of liver fibrosis. The novel automated assay is a reliable and easily
      applicable method for total plasma antioxidant response measurement in
      nonalcoholic steatohepatitis.

PMID- 16283936
TI  - Inteins and affinity resin substitutes for protein purification and scale up.
AB  - The development of self-cleaving fusion-tag technology has greatly simplified the
      purification of recombinant proteins at laboratory scale. The self-cleaving
      capability of these tags has recently been combined with additional purification
      tags to generate novel and convenient protein purification methods at a variety
      of scales. In this review, we describe some of these methods, and provide a
      rudimentary economic analysis of hypothetical large-scale applications. This work
      is expected to provide a rough outline for the evaluation of these methods for
      large-scale bioprocessing of a variety of products.

PMID- 16283937
TI  - The Australia-modified Karnofsky Performance Status (AKPS) scale: a revised scale
      for contemporary palliative care clinical practice [ISRCTN81117481].
AB  - BACKGROUND: The Karnofsky Performance Status (KPS) is a gold standard scale. The
      Thorne-modified KPS (TKPS) focuses on community-based care and has been shown to
      be more relevant to palliative care settings than the original KPS. The Australia
      modified KPS (AKPS) blends KPS and TKPS to accommodate any setting of care.
      METHODS: Performance status was measured using all three scales for palliative
      care patients enrolled in a randomized controlled trial in South Australia. Care
      occurred in a range of settings. Survival was defined from enrollment to death.
      RESULTS: Ratings were collected at 1600 timepoints for 306 participants. The
      median score on all scales was 60. KPS and AKPS agreed in 87% of ratings; 79% of
      disagreements occurred within 1 level on the 11-level scales. KPS and TKPS agreed
      in 76% of ratings; 85% of disagreements occurred within one level. AKPS and TKPS
      agreed in 85% of ratings; 87% of disagreements were within one level. Strongest
      agreement occurred at the highest levels (70-90), with greatest disagreement at
      lower levels (< or =40). Kappa coefficients for agreement were KPS-TKPS 0.71, KPS
      AKPS 0.84, and AKPS-TKPS 0.82 (all p < 0.001). Spearman correlations with
      survival were KPS 0.26, TKPS 0.27 and AKPS 0.26 (all p < 0.001). AKPS was most
      predictive of survival at the lower range of the scale. All had longitudinal test
      retest validity. Face validity was greatest for the AKPS. CONCLUSION: The AKPS is
      a useful modification of the KPS that is more appropriate for clinical settings
      that include multiple venues of care such as palliative care.

PMID- 16283939
TI  - Supply-demand balance in outward-directed networks and Kleiber's law.
AB  - BACKGROUND: Recent theories have attempted to derive the value of the exponent
      alpha in the allometric formula for scaling of basal metabolic rate from the
      properties of distribution network models for arteries and capillaries. It has
      recently been stated that a basic theorem relating the sum of nutrient currents
      to the specific nutrient uptake rate, together with a relationship claimed to be
      required in order to match nutrient supply to nutrient demand in 3-dimensional
      outward-directed networks, leads to Kleiber's law (b = 3/4). METHODS: The
      validity of the supply-demand matching principle and the assumptions required to
      prove the basic theorem are assessed. The supply-demand principle is evaluated by
      examining the supply term and the demand term in outward-directed lattice models
      of nutrient and water distribution systems and by applying the principle to
      fractal-like models of mammalian arterial systems. RESULTS: Application of the
      supply-demand principle to bifurcating fractal-like networks that are outward
      directed does not predict 3/4-power scaling, and evaluation of water distribution
      system models shows that the matching principle does not match supply to demand
      in such systems. Furthermore, proof of the basic theorem is shown to require that
      the covariance of nutrient uptake and current path length is 0, an assumption
      unlikely to be true in mammalian arterial systems. CONCLUSION: The supply-demand
      matching principle does not lead to a satisfactory explanation for the
      approximately 3/4-power scaling of mammalian basal metabolic rate.

PMID- 16283938
TI  - Testing for adaptive evolution of the female reproductive protein ZPC in mammals,
      birds and fishes reveals problems with the M7-M8 likelihood ratio test.
AB  - BACKGROUND: Adaptive evolution appears to be a common feature of reproductive
      proteins across a very wide range of organisms. A promising way of addressing the
      evolutionary forces responsible for this general phenomenon is to test for
      adaptive evolution in the same gene but among groups of species, which differ in
      their reproductive biology. One can then test evolutionary hypotheses by asking
      whether the variation in adaptive evolution is consistent with the variation in
      reproductive biology. We have attempted to apply this approach to the study of a
      female reproductive protein, zona pellucida C (ZPC), which has been previously
      shown by the use of likelihood ratio tests (LRTs) to be under positive selection
      in mammals. RESULTS: We tested for evidence of adaptive evolution of ZPC in 15
      mammalian species, in 11 avian species and in six fish species using three
      different LRTs (M1a-M2a, M7-M8, and M8a-M8). The only significant findings of
      adaptive evolution came from the M7-M8 test in mammals and fishes. Since LRTs of
      adaptive evolution may yield false positives in some situations, we examined the
      properties of the LRTs by several different simulation methods. When we simulated
      data to test the robustness of the LRTs, we found that the pattern of evolution
      in ZPC generates an excess of false positives for the M7-M8 LRT but not for the
      M1a-M2a or M8a-M8 LRTs. This bias is strong enough to have generated the
      significant M7-M8 results for mammals and fishes. CONCLUSION: We conclude that
      there is no strong evidence for adaptive evolution of ZPC in any of the
      vertebrate groups we studied, and that the M7-M8 LRT can be biased towards false
      inference of adaptive evolution by certain patterns of non-adaptive evolution.

PMID- 16283940
TI  - Prevalence of Helicobacter pylori infection and associated factors among adults
      in Southern Brazil: a population-based cross-sectional study.
AB  - BACKGROUND: Helicobacter pylori (Hp) infection is associated with several upper
      gastrointestinal disorders. Local data on the epidemiology of the infection are
      scarce in Brazil. The purpose of this study is to measure the prevalence rate and
      to explore the associated factors among the adult population living in Pelotas, a
      southern Brazilian city. METHODS: This was a population-based cross-sectional
      study. Through a multi-stage sampling method all individuals 20 years and over
      living at the selected households at the urban area of the city were interviewed
      regarding past and current socio-economic indicators; demographic
      characteristics; nutritional and behavioural habits; and history of upper
      gastrointestinal symptoms.Hp infection was ascertained through the 13C-UBT. Due
      to the high prevalence, data were analysed through robust Poisson regression. All
      analyses took into account the family clustering of the data. RESULTS: Among 563
      eligible individuals, 363 agreed to perform the 13C-UBT (refusal rate of 35.5%).
      Refusals were associated with female sex, consumption of mate drinking, and
      presence of upper gastrointestinal symptoms. The prevalence rate of H. pylori
      infection was 63.4% (95%CI 59.3%-69.3%). In crude analyses, prevalence was
      associated with increasing age, non-white skin colour, lower current family
      income, lower education level, higher size of the family, low socio-economic
      conditions in childhood, higher number of siblings and attendance to day-care
      centres in childhood, and presence of dyspeptic symptoms. In adjusted analysis
      the level of education of the father was inversely associated with the infection,
      whereas number of siblings and attendance to day-care centre in childhood were
      directly associated with it. Non-white skin colour remained significantly
      associated with increased prevalence even after allowing for past and current
      socio-economic characteristics, age and sex. Compared to non-symptomatic
      individuals, those reporting dyspeptic symptoms presented a higher prevalence of
      the infection even after allowing for current and past socio-economic conditions,
      ethnicity, age, and sex. CONCLUSION: Hp infection is as common among adults in
      southern Brazil as it is in other developing countries. Socio-economic conditions
      in childhood besides ethnicity and presence of dyspeptic symptoms were the
      factors significantly associated with the infection.

PMID- 16283941
TI  - Inter-population variations in concentrations, determinants of and correlations
      between 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p
      chlorophenyl)-ethylene (p,p'-DDE): a cross-sectional study of 3161 men and women
      from Inuit and European populations.
AB  - BACKGROUND: The study is part of a collaborative project (Inuendo), aiming to
      assess the impact of dietary persistent organochlorine pollutants (POPs) on human
      fertility. The aims with the present study are to analyze inter-population
      variations in serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153)
      and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE), to assess inter
      population variations in biomarker correlations, and to evaluate the relative
      impact of different determinants for the inter-individual variations in POP
      biomarkers. METHOD: In study populations of 3161 adults, comprising Greenlandic
      Inuits, Swedish fishermen and their wives, and inhabitants from Warsaw, Poland
      and Kharkiv, Ukraine, serum concentrations of CB-153 and p,p'-DDE, were analysed
      by gas chromatography-mass spectrometry. RESULTS: The median serum concentrations
      of CB-153 were for male and female Inuits 200 and 110, for Swedish fishermen 190
      and their wives 84, for Kharkiv men and women 44 and 27, and for Warsaw men and
      women 17 and 11 ng/g lipids, respectively. The median serum concentrations of
      p,p'-DDE were for Kharkiv men and women 930 and 650, for male and female Inuits
      560 and 300, for Warsaw men and women 530 and 380, and for Swedish fishermen 240
      and their wives 140 ng/g lipids, respectively. The correlation coefficients
      between CB-153 and p,p'-DDE varied between 0.19 and 0.92, with the highest
      correlation among Inuits and the lowest among men from Warsaw. Men had averagely
      higher serum concentrations of CB-153 and p,p'-DDE, and there were positive
      associations between age and the POP-biomarkers, whereas the associations with
      BMI and smoking were inconsistent. Dietary seafood was of importance only in the
      Inuit and Swedish populations. CONCLUSION: CB-153 concentrations were much higher
      in Inuits and Swedish fishermen's populations than in the populations from
      Eastern Europe, whereas the pattern was different for p,p'-DDE showing highest
      concentrations in the Kharkiv population. The correlations between the POP
      biomarkers varied considerably between the populations, underlining that exposure
      sources differ and that the choice of representative biomarkers of overall POP
      exposure has to be based on an analysis of the specific exposure situation for
      each population. Age and gender were consistent determinants of serum POPs;
      seafood was of importance only in the Inuit and Swedish populations.

PMID- 16283942
TI  - Paucity of chimeric gene-transposable element transcripts in the Drosophila
      melanogaster genome.
AB  - BACKGROUND: Recent analysis of the human and mouse genomes has shown that a
      substantial proportion of protein coding genes and cis-regulatory elements
      contain transposable element (TE) sequences, implicating TE domestication as a
      mechanism for the origin of genetic novelty. To understand the general role of TE
      domestication in eukaryotic genome evolution, it is important to assess the
      acquisition of functional TE sequences by host genomes in a variety of different
      species, and to understand in greater depth the population dynamics of these
      mutational events. RESULTS: Using an in silico screen for host genes that contain
      TE sequences, we identified a set of 63 mature "chimeric" transcripts supported
      by expressed sequence tag (EST) evidence in the Drosophila melanogaster genome.
      We found a paucity of chimeric TEs relative to expectations derived from non
      chimeric TEs, indicating that the majority (approximately 80%) of TEs that
      generate chimeric transcripts are deleterious and are not observed in the genome
      sequence. Using a pooled-PCR strategy to assay the presence of gene-TE chimeras
      in wild strains, we found that over half of the observed chimeric TE insertions
      are restricted to the sequenced strain, and approximately 15% are found at high
      frequencies in North American D. melanogaster populations. Estimated population
      frequencies of chimeric TEs did not differ significantly from non-chimeric TEs,
      suggesting that the distribution of fitness effects for the observed subset of
      chimeric TEs is indistinguishable from the general set of TEs in the genome
      sequence. CONCLUSION: In contrast to mammalian genomes, we found that fewer than
      1% of Drosophila genes produce mRNAs that include bona fide TE sequences. This
      observation can be explained by the results of our population genomic analysis,
      which indicates that most potential chimeric TEs in D. melanogaster are
      deleterious but that a small proportion may contribute to the evolution of novel
      gene sequences such as nested or intercalated gene structures. Our results
      highlight the need to establish the fixity of putative cases of TE domestication
      identified using genome sequences in order to demonstrate their functional
      importance, and reveal that the contribution of TE domestication to genome
      evolution may vary drastically among animal taxa.

PMID- 16283943
TI  - Dynamic regulation of integrin activation by intracellular and extracellular
      signals controls oligodendrocyte morphology.
AB  - BACKGROUND: Myelination requires precise control of oligodendrocyte morphology
      and myelin generation at each of the axons contacted by an individual cell. This
      control must involve the integration of extracellular cues, such as those on the
      axon surface, with intrinsic developmental programmes. We asked whether integrins
      represent one class of oligodendrocyte cell-surface receptors able to provide
      this integration. RESULTS: Integrins signal via a process of activation, a
      conformational change that can be induced either by "outside-in" signals
      comprising physiological extracellular matrix ligands (mimicked by the
      pharmacological use of the divalent cation manganese) or "inside-out" signalling
      molecules such as R-Ras. Increasing levels of outside-in signalling via the
      laminin receptor alpha6beta1 integrin were found to promote oligodendrocyte
      processing and myelin sheet formation in culture. Similar results were obtained
      when inside-out signalling was increased by the expression of a constitutively
      active R-Ras. Inhibiting inside-out signalling by using dominant-negative R-Ras
      reduces processes and myelin sheets; importantly, this can be partially rescued
      by the co-stimulation of outside-in signalling using manganese. CONCLUSION: The
      balance of the equilibrium between active and inactive integrins regulates
      oligodendrocyte morphology, which is itself regulated by extrinsic and intrinsic
      cues so providing a mechanism of signal integration. As laminins capable of
      providing outside-in signals are present on axons at the time of myelination, a
      mechanism exists by which morphology and myelin generation might be regulated
      independently in each oligodendrocyte process.

PMID- 16283944
TI  - Health problems and help-seeking activities of methadone maintenance clients at
      Auckland Methadone Service (AMS): potential for community pharmacy service
      expansion?
AB  - BACKGROUND: In general the health of methadone clients has been found to be
      poorer than that of the general population. In New Zealand specialist drug
      services are not funded to provide primary healthcare services. Many health
      conditions could potentially be managed by community pharmacists who have
      frequent contact with this client group. This study sought to explore the health
      problems suffered by methadone clients, who they sought help from, and the
      potential for greater involvement of pharmacists. METHODS: Self-completion
      questionnaire of methadone maintenance clients managed in specialist care in
      Auckland, New Zealand. RESULTS: The most common health problem experienced by
      these clients in the past three months was sweating (70.0%), and more than half
      of the respondents also reported experiencing headache, fatigue and depression.
      The least frequently experienced conditions were hay fever (12.9%) and abscesses
      (12.1%). Respondents indicated that the top three choices from whom they would
      seek help were GP (56.7%), the client's partner (31.6%) and community pharmacists
      (27.9%). Barriers to seeking help from pharmacists included issues around cost,
      perceptions of pharmacist knowledge and skills, privacy and confidentiality.
      CONCLUSION: Methadone clients in this study indicated that they suffered a number
      of general health problems, and in many cases were likely to seek help from a GP
      or their own partner, before seeking help from pharmacists. However, for over one
      quarter of respondents the pharmacist was in the top three from whom they would
      seek advice. Any barriers towards consulting pharmacists, in the main seem to be
      resolvable.

PMID- 16283945
TI  - Cancer incidence in the south Asian population of California, 1988-2000.
AB  - BACKGROUND: Although South Asians (SA) form a large majority of the Asian
      population of U.S., very little is known about cancer in this immigrant
      population. SAs comprise people having origins mainly in India, Pakistan,
      Bangladesh and Sri Lanka. We calculated age-adjusted incidence and time trends of
      cancer in the SA population of California (state with the largest concentration
      of SAs) between 1988-2000 and compared these rates to rates in native Asian
      Indians as well as to those experienced by the Asian/Pacific Islander (API) and
      White, non-Hispanic population (NHW) population of California. METHODS: Age
      adjusted incidence rates observed among the SA population of California during
      the time period 1988-2000 were calculated. To correctly identify the ethnicity of
      cancer cases, 'Nam Pehchan' (British developed software) was used to identify
      numerator cases of SA origin from the population-based cancer registry in
      California (CCR). Denominators were obtained from the U.S. Census Bureau.
      Incidence rates in SAs were calculated and a time trend analysis was also
      performed. Comparison data on the API and the NHW population of California were
      also obtained from CCR and rates from Globocan 2002 were used to determine rates
      in India. RESULTS: Between 1988-2000, 5192 cancers were diagnosed in SAs of
      California. Compared to rates in native Asian Indians, rates of cancer in SAs in
      California were higher for all sites except oropharyngeal, oesophageal and
      cervical cancers. Compared to APIs of California, SA population experienced more
      cancers of oesophagus, gall bladder, prostate, breast, ovary and uterus, as well
      as lymphomas, leukemias and multiple myelomas. Compared to NHW population of
      California, SAs experienced more cancers of the stomach, liver and bile duct,
      gall bladder, cervix and multiple myelomas. Significantly increasing time trends
      were observed in colon and breast cancer incidence. CONCLUSION: SA population of
      California experiences unique patterns of cancer incidence most likely associated
      with acculturation, screening and tobacco habits. There is need for early
      diagnosis of leading cancers in SA. If necessary steps are not taken to curb the
      growth of breast, colon and lung cancer, rates in SA will soon approximate those
      of the NHW population of California.

PMID- 16283946
TI  - Case-control study of sudden infant death syndrome in Lithuania, 1997-2000.
AB  - BACKGROUND: To identify risk factors for sudden infant death syndrome relevant in
      Lithuania. METHODS: A nationwide case-control study surveying parents of 35
      infants who died from sudden infant death syndrome during the period of 1997-2000
      and parents of 145 control infants matched with SIDS infants for date of birth
      and for region of birth was carried out. RESULTS: Deaths incidence was greater in
      the warm period (60%) vs. cold period (40%). Prone and side sleeping positions
      both carried no increased risk of sudden infant death syndrome compared with
      supine because of a rare prone sleeping (4.1% of controls vs. 0% of dead infants)
      and more prevalent side than supine sleeping (84.8% of controls vs. 94.3% of dead
      infants) in the controls as well as the cases. Bed sharing for the whole night as
      a risk factor for sudden infant death syndrome has not been confirmed, either, as
      bed sharing was common only for the controls (13.8% of controls vs. 0% of dead
      infants). Routine sleeping environment factors such as heavy wrapping (> or =4
      togs) of an infant (odds ratio 8.49; 95% confidence interval 2.38 to 30.32),
      sleeping in a bassinet (4.22; 1.16 to 15.38) and maternal factors such as
      maternal education < or =12 years (4.48; 1.34 to 14.94), unplanned pregnancy
      (5.22; 1.49 to 18.18) and > or =2 previous live births (3.90; 1.00 to 15.10) were
      significantly associated with sudden infant death syndrome on multivariate
      analysis. CONCLUSION: The results of this first population-based case-control
      study have shed some light on the epidemiology of the syndrome in Lithuania.
      Although the mortality of sudden infant death syndrome in Lithuania is not high,
      it might be lowered moreover by public informing about sudden infant death
      syndrome and related risk factors. Special attention must be paid to mothers with
      low education on potentially modifiable risk factors such as routine heavy
      wrapping of an infant during sleep, routine sleeping in a bassinet and unplanned
      pregnancy.

PMID- 16283947
TI  - The European DISABKIDS project: development of seven condition-specific modules
      to measure health related quality of life in children and adolescents.
AB  - BACKGROUND: The European DISABKIDS project aims to enhance the Health Related
      Quality of Life (HRQoL) of children and adolescents with chronic medical
      conditions and their families. We describe the development of the seven cross
      nationally tested condition-specific modules of the European DISABKIDS HRQoL
      instrument in a population of children and adolescents. The condition-specific
      modules are intended for use in conjunction with the DISABKIDS chronic generic
      module. METHODS: Focus groups were used to construct the pilot version of the
      DISABKIDS condition-specific HRQoL modules for asthma, juvenile idiopathic
      arthritis, atopic dermatitis, cerebral palsy, cystic fibrosis, diabetes and
      epilepsy. Analyses were conducted on pilot test data in order to construct field
      test versions of the modules. A series of factor analyses were run, first, to
      determine potential structures for each condition-specific module, and, secondly,
      to select a reduced number of items from the pilot test to be included in the
      field test. Post-field test analyses were conducted to retest the domain
      structure for the final DISABKIDS condition-specific modules. RESULTS: The
      DISABKIDS condition-specific modules were tested in a pilot study of 360
      respondents, and subsequently in a field test of 1152 respondents in 7 European
      countries. The final condition-specific modules consist of an 'Impact' domain and
      an additional domain (e.g. worry, stigma, treatment) with between 10 to 12 items
      in total. The Cronbach's alpha of the final domains was found to vary from 0.71
      to 0.90. CONCLUSION: The condition-specific modules of the DISABKIDS instrument
      were developed through a step-by-step process including cognitive interview,
      clinical expertise, factor analysis, correlations and internal consistency. A
      cross-national pilot and field test were necessary to collect these data. In
      general, the internal consistency of the domains was satisfactory to high. In
      future, the DISABKIDS instrument may serve as a useful tool with which to assess
      HRQoL in children and adolescents with a chronic condition. The condition
      specific modules can be used in conjunction with the DISABKIDS chronic generic
      module.

PMID- 16283948
TI  - A new, fast and semi-automated size determination method (SASDM) for studying
      multicellular tumor spheroids.
AB  - BACKGROUND: Considering the width and importance of using Multicellular Tumor
      Spheroids (MTS) in oncology research, size determination of MTSs by an accurate
      and fast method is essential. In the present study an effective, fast and semi
      automated method, SASDM, was developed to determinate the size of MTSs. The
      method was applied and tested in MTSs of three different cell-lines. Frozen
      section autoradiography and Hemotoxylin Eosin (H&E) staining was used for further
      confirmation. RESULTS: SASDM was shown to be effective, user-friendly, and time
      efficient, and to be more precise than the traditional methods and it was
      applicable for MTSs of different cell-lines. Furthermore, the results of image
      analysis showed high correspondence to the results of autoradiography and
      staining. CONCLUSION: The combination of assessment of metabolic condition and
      image analysis in MTSs provides a good model to evaluate the effect of various
      anti-cancer treatments.

PMID- 16283950
TI  - Birth order and sexual orientation in men: evidence for two independent
      interactions.
AB  - Birth order is correlated with male sexual orientation, but the reason(s) for
      this relationship is unclear. In the present study, data from a Canadian sample
      of homosexual and heterosexual men (N=604) were used to present evidence of two
      independent birth order interactions--one with height and the other with parental
      age--predicting sexual orientation in men. If these findings prove reliable, it
      raises the possibility that different aetiological factors underlie the birth
      order/sexual orientation relationship in men.

PMID- 16283949
TI  - Concordance of Helicobacter pylori infection among children in extended-family
      homes.
AB  - Helicobacter pylori is transmitted within households and high concordance is
      observed among siblings. To better understand the contributions of close
      interpersonal contact and family relatedness to transmission, we compared
      concordance of H. pylori infection among 241 sibling and non-sibling children
      aged 2-18 years in 68, predominantly low-income, Hispanic households with at
      least two nuclear families. Prevalence of H. pylori infection was 24%. Compared
      to children with no infected siblings or non-siblings and adjusting for age, odds
      of H. pylori infection were 1.2 (95% CI 0.52-2.9), 3.2 (95% CI 1.14-9.1), and 9.4
      (95% CI 3.1-28.5) for children residing with at least one infected non-sibling,
      one infected sibling, and with at least one infected sibling and non-sibling,
      respectively. The study further implicates intersibling transmission as a pathway
      for H. pylori infection in childhood. In addition, living with a non-sibling in
      extended-family homes may contribute to infection risk but only in households
      with prevalent H. pylori infection within all family groups.

PMID- 16283951
TI  - Use of 'sense of coherence (SOC)' scale to measure resilience in Eritrea:
      interrogating both the data and the scale.
AB  - An adapted 'sense of coherence' scale short form (SOC-13) was administered in
      nine languages of Eritrea with a total of 265 participants (162 women and 103
      men) in order to assess 'resilience' in quantitative terms. Statistical analysis
      yielded significant differences in SOC scores between the displaced and non
      displaced: mean=54.84 (SD=6.48) in internally displaced person (IDP) camps,
      compared with mean=48.94 (SD=11.99) in urban and rural settlements (t=3.831,
      p<0.001). Post-hoc tests revealed that the main difference is between IDP camp
      dwellers and urban (non-displaced) residents. Those in rural but traditionally
      mobile (pastoralist or transhumant) communities scored more or less the same as
      the urban non-displaced - i.e. significantly higher than those in IDP camps
      (p<0.05). Analysis of variance showed that displacement has a significantly
      negative effect on women compared with men (RR=0.262, p<0.001). Repeating the
      analysis for the three groups confirmed that urban and pastoralist/transhumant
      groups are similar, while women in IDP camps are lower scoring (RR=0.268,
      p<0.001), Hamboka women being worst affected due to their experience of serial
      displacement. These findings are interpreted and discussed in the light of
      qualitative information gleaned from the study participants' interrogation of the
      content of the SOC scale; and in the wider context of historical, socio-political
      and cultural characteristics of Eritrea. The study's implications for
      humanitarian and public health policy are considered.

PMID- 16283952
TI  - Epidemiological reflections of the contribution of anthropology to public health
      policy and practice.
AB  - Academic disciplines like anthropology and epidemiology provide a niche for
      researchers to speak the same language, and to interrogate the assumptions that
      they use to investigate problems. How anthropological and epidemiological methods
      communicate and relate to each other affects the way public health policy is
      created but the philosophical underpinnings of each discipline makes this
      difficult. Anthropology is reflective, subjective and investigates complexity and
      the individual; epidemiology, in contrast, is objective and studies populations.
      Within epidemiological methods there is the utilitarian concept of potentially
      sacrificing the interests of the individual for the benefits of maximizing
      population welfare, whereas in anthropology the individual is always included.
      Other strengths of anthropology in the creation of public health policy include:
      its attention to complexity, questioning the familiar; helping with language and
      translation; reconfiguring boundaries to create novel frameworks; and being
      reflective. Public health requires research that is multi-, inter- and trans
      disciplinary. To do this, there is a need for each discipline to respect the
      'dignity of difference' between disciplines in order to help create appropriate
      and effective public health policy.

PMID- 16283953
TI  - [Multidisciplinary treatment for rectal cancer: evolving or at a standstill?].

PMID- 16283954
TI  - [Modification of the presentation of ocular trauma by age group in an urban
      Mexican population].
AB  - INTRODUCTION: We identified whether ocular trauma presentation, according to the
      system for classifying mechanical injuries of the eye, had modifications among
      different age groups, which could be useful as damage predictors during the
      initial evaluation of these patients. MATERIAL AND METHODS: Ocular trauma
      referrals between 1995 and 2003 were re-qualified according to the system for
      classifying mechanical injuries. Patients were divided into 5-year groups and the
      most frequent categories of type, grade, pupil and zone were determined by group.
      Mean age of each category and the rate of categories between groups were compared
      (ANOVA and Kruskal-Wallis, chi2 and odds ratio [OR]). RESULTS: Five hundred sixty
      six eyes of 551 patients were evaluated (age: 0.5-90 years, mean age: 27.7); mean
      age was lower for type B closed globe trauma and zone II (p < 0.05). There was a
      higher rate of grade 1 in patients > 60 years (OR 3.8), of grade 4 in patients <
      54 years (OR 3.25) and of type B closed globe in patients > 20 years (OR 3.3).
      The remaining comparisons showed no clinical differences. CONCLUSIONS: There were
      no significant modifications in the presentation of most of the categories
      between age groups. Age difference was not useful as a predictor for detecting
      traumatic ocular damage.

PMID- 16283955
TI  - [Esophageal atresia: a second-level hospital experience].
AB  - INTRODUCTION: In recent years, surgical correction of esophageal atresia with
      distal tracheoesophageal fistula has become increasingly successful. However,
      there is still a group of high-risk patients with specific factors in whom the
      mortality remains appreciable. These associated factors include weight,
      gestational age, associated malformations and respiratory distress. MATERIAL AND
      METHODS: This report analyzes the mortality in 80 newborn infants with variants
      of esophageal atresia with or without tracheoesophageal fistula who were treated
      from 1999 to 2003. Data were collected restrospectively from hospital and office
      records. RESULTS: We observed 42 male patients, 69 patients were C variety, all
      had more than 12 h of postnatal life, 34 were preterm newborn, 41 were classified
      A or B according to Waterston, and 41 died. A logistic regression analysis and
      chi2 of the influence of each risk factor on mortality was performed. Relevant
      statistical significance was found in the studied variables. CONCLUSIONS:
      Morbidity and mortality of esophageal atresia was higher due to identified risk
      factors.

PMID- 16283956
TI  - [Necrotizing mediastinitis in deep neck infections].
AB  - INTRODUCTION: Mediastinitis is a rare complication of deep neck abscesses with a
      high mortality. An accelerated extension to the mediastinum can happen before the
      identification of the primary site of infection, delaying diagnosis and
      treatment. OBJECTIVE: To report the results of treatment of patients with
      mediastinitis as a complication of deep neck infection. MATERIAL AND METHODS:
      Case series. Consecutive patients with mediastinitis secondary to deep neck
      abscesses, from March 2001 to February 2004. RESULTS: We studied five patients:
      three males (60%) and two females (40%), mean age 42.2 +/- 18.4 years. In all
      patients there was at least a 3-day delay before appropriate diagnosis was made.
      Hospitalization ranged between 1 and 56 days. Symptoms were fever in five cases
      (100%), dysphagia in four (80%), dyspnea in four (80%), retrosternal pain in
      three (60%), orthopnea in two (40%), and tachycardia in one (20%). Primary
      infection sites were of dental origin in four cases (80%) and upper respiratory
      tract infection in one. Surgical management consisted of cervical and mediastinal
      drainage with tracheotomy in all patients (100%). Three also required pleurostomy
      and two required gastrostomy to improve nutritional status. Mean number of
      surgical procedures was 5.4 +/- 1.8. All patients developed respiratory
      insufficiency requiring mechanical ventilation. Mortality was 60%. CONCLUSIONS:
      The delayed diagnosis was common in this case series. The length of
      hospitalization was long because patients required management with ventilatory
      support and multiple surgical procedures to limit the infectious process. High
      mortality is an indication for the early identification and treatment of all
      cases.

PMID- 16283957
TI  - [Ventricular rupture in mitral valve surgery. Five-year experience].
AB  - OBJECTIVE: We present our 5-year experience in ventricular rupture in mitral
      valve surgery. MATERIAL AND METHODS: We analyzed all patients submitted to mitral
      valvular surgery between January 1st, 1997 and December 31, 2001. Incidence and
      type of rupture, technique for repair and morbi-mortality were analyzed. RESULTS:
      Mitral valve surgery was performed in 1151 patients with different modalities.
      Seventeen patients (5 male and 12 female) had ventricular rupture. The incidence
      was 1.47%. Mean age was 55 years. Four (23%) were in the right ventricle and 13
      (76%) in left ventricle and atrioventricular groove. Of all ruptures, nine
      (52.9%) were in the simple mitral valve, three (17.6%) in mitroaortic surgery,
      two (11.7%) in mitral prosthetic replacement, two (11.7%) in mitro-tricuspid
      surgery and only one (5.8%) in mitral prosthetic valve resuture secondary to
      paravalvular leak. Six (35.2%) survived; two (11.7%) had right ventricular
      rupture and four (23.5%) had left ventricular rupture. CONCLUSIONS: Incidence and
      mortality of this complication in our study group has seldom appeared in the
      literature worldwide. The most successful surgical method was the sandwich repair
      technique with Teflon strips and polypropylene suture plus packing.

PMID- 16283958
TI  - [Cervical epidural anesthesia for upper extremity surgery using three different
      formulations of local anesthetics].
AB  - OBJECTIVE: To evaluate the efficiency and safety of the cervical epidural
      blockade (CEB) in upper extremity surgery, using lidocaine 2%, bupivacaine 5% and
      a mixture of both local analgesics. MATERIAL AND METHODS: Eighty five patients
      were submitted to upper limb surgery under CEB. They were assigned into one of
      three groups: group I received 100 mg of 2% lidocaine; group II received 30 mg of
      0.5% bupivacaine, and group III received a mixture of 60 mg of 2% lidocaine and
      15 mg of 0.5% bupivacaine. We evaluated their effects on vital signs, blockade
      quality, adverse effects, and patient comfort. RESULTS: Anesthesiologist and
      surgeon evaluated the technique as "good" in 80% of the patients. Significant
      differences were found for motor blockade. Group II developed complete motor
      block (100%). Observed adverse effects were vomiting in groups II and III and
      dural puncture was present in 6.7% of the cases in group II. CONCLUSIONS: This
      study confirms the safety of cervical epidural anesthesia for upper limb surgery
      using three different formulations of local anesthetics.

PMID- 16283959
TI  - [Colon aganglionosis in patients with anorectal malformation. Analysis of five
      cases].
AB  - INTRODUCTION: The association of colon aganglionosis and anorectal malformation
      is very rare. The objective is to show five clinical cases of anorectal
      malformation associated with Hirschprung's disease and its treatment and
      evolution. MATERIAL AND METHODS: A retrospective, transverse, descriptive study
      was carried out at the National Medical Center "20 de Noviembre ISSSTE" from 1984
      to 1999 that included all files of patients with anorectal malformation
      associated with Hirschprung's disease corroborated by histopathological studies.
      RESULTS: From 151 patients with anorectal malformation studied during a period of
      15 years, there were five cases (3.2%) of patients found with anorectal
      malformation associated with Hirschprung's disease. Of these, two were female.
      Three patients presented with lower anorectal malformation and two with high
      anorectal malformation. CONCLUSIONS: The association of colon aganglionosis and
      anorectal malformation should be suspected when the patient evolution during the
      postoperative period presents abdominal distension, constipation, urinary
      infection and in younger children with necrotizing enterocolitis.

PMID- 16283960
TI  - [Hydration status and aerobic capacity: effects on plasmatic volume during
      strenuous physical exercise].
AB  - INTRODUCTION: During exercise, water loss frequently occurs in the intracellular
      spaces and there is a decrease in the plasmatic volume, with a blood
      concentration as a secondary characteristic. Plasmatic volume losses provoke a
      decrease in the blood flow, which directly affects cardiac function. Physical
      performance decreases and aerobic capacity deteriorates. MATERIAL AND METHODS: An
      observational, prospective, longitudinal, and comparative study was carried out
      to evaluate gender influence and the aerobic capacity level upon hydration and
      the plasmatic volume produced by maximal physical exercise. Twenty four
      individuals between 18 and 35 years old were included. All participated in
      aerobic physical exercise and changes in hemoglobin, hematocrit, plasmatic
      volume, and hydration state were evaluated. RESULTS: Gender showed a significant
      influence on plasmatic volume but not on the hydration state. The aerobic
      capacity presented a relationship with plasmatic volume, and the plasmatic volume
      with the hydration state. Women presented more plasmatic volume loss than men (p
      < 0.05). Individuals who have adequate aerobic capacity tend to lose less
      plasmatic volume during exercise. CONCLUSIONS: Maximal physical exercise during a
      short period also leads to important liquid loss; therefore, it is important that
      people who engage in exercise understand their liquid losses and re-hydrate
      themselves appropriately before, during, and after exercise.

PMID- 16283961
TI  - [Sleep alterations in childhood victims of sexual and physical abuse].
AB  - INTRODUCTION: The abused child syndrome is related to a variety of emotional
      disorders, among which are the "post-traumatic stress syndrome" and the phenomena
      "re-experience," which is related to disturbances of the normal sleep-wake cycle.
      OBJECTIVE: To determine the polysomnographic characteristics of the abused child
      syndrome and compare them with paired healthy children. MATERIAL AND METHODS:
      After two-night habituation, all-night video-digital polygraphic recordings
      following recommendations of the International Federation of Clinical
      Neurophysiology were performed in 15 abused child syndrome and 15 healthy
      controls. RESULTS: In the abused child syndrome patients, the main sleep changes
      were decreased sleep efficiency, decreased sleep onset sleep latency, increased
      wakefulness, decreased REM sleep and total sleep time. CONCLUSIONS: The abused
      child syndrome have abnormal sleep patterns, independent of the type of abuse,
      age or sex. Sleep alterations are a new characteristic of the abused child
      syndrome, not previously described.

PMID- 16283962
TI  - [Ultrasonography with contrast agent for diagnosis of benign retroperitoneal
      cyst. Case report].
AB  - Intraabdominal tumors require precise diagnosis for patient preparation for
      optimal surgical procedure. For diagnosis of these lesions, the principal studies
      used are ultrasonography, computed axial tomography (CAT) and occasionally the
      use of magnetic resonance imaging, a study not always possible to accomplish in
      all hospitals. We present the case of a patient with a giant retroperitoneal cyst
      whose diagnosis was missed by means of conventional ultrasound and CAT. For this
      reason, we chose to use ultrasound with echography using contrast agent
      (Levovist) to determine if the tumor was dependent on the liver or pancreas. By
      means of this technique, we were able to make the diagnosis that the tumor did
      not depend on any organ, but rather was an independent retroperitoneal tumor.
      Final surgical and histopathological diagnosis was a retroperitoneal multilocular
      lymphangioma. We conclude that ultrasonography with contrast agent (Levovist) is
      an alternative method for studying intraabdominal tumors.

PMID- 16283963
TI  - [Conservative management of postoperative lymphatic fistula].
AB  - We describe the case of a diabetic patient who presented with a renal abscess
      that was surgically managed with nephrectomy. At the forth post-surgical day, the
      patient showed the presence of a "milky" looking fluid amounting to 1200 ml in 24
      h through a Penrose drainage placed in the surgical resection site. After several
      studies, a diagnosis of lymphatic fistula was made. The first dietary management
      technique tried was not satisfactory, and total parenteral nutrition management
      was decided upon, obtaining a satisfactory outcome within a few days. We reviewed
      the literature where we found scant reported information on lymphatic fistulas
      following retroperitoneal surgery and we consider that because of more aggressive
      surgical techniques and more advanced technology for increased patient survival,
      doctors will witness a higher incidence of chylous fistulas or chylous ascites,
      which is why it is important to be aware of this complication.

PMID- 16283964
TI  - [Appendiceal stump appendicitis. Case report].
AB  - Acute appendicitis is still the first cause of abdominal surgery worldwide, with
      1.4 cases/1000 in the general population. As frequent as this is, appendiceal
      stump appendicitis is a very rare surgical event, due to an incomplete appendix
      resection and misleading cecum base identification due to cecum edema, abscesses,
      abnormal anatomy position of the appendix or multiple adhesions. The incidence of
      appendiceal stump appendicitis is not well known; however, there are some reports
      that suggest a slight increase in this pathology possibly due to laparoscopic
      surgical techniques. This report attempts to point out this diagnostic
      possibility to be considered by the surgeon when presented with a patient with
      acute abdominal pain and a past appendectomy.

PMID- 16283965
TI  - [Histopathologic study of the frontolateral laryngectomy specimen: topics of
      clinical interest].
AB  - Frontolateral laryngectomy is a surgical procedure that allows removal of a vocal
      cord, anterior commissure, one third of the healthy vocal cord and the thyroid
      cartilage keel. It is indicated in patients with T1a and T1b glottic-located
      carcinomas with adverse prognosis factors and selected T2 cases. The success
      relies on appropriate tumor excision. In order to make an assessment, we need to
      know the critical topics of clinic interest in the histopathologic study of the
      specimen. The objective is to analyze which are the significant factors to
      histologically assess in frontolateral laryngectomy and to report the
      histological study technique conducted at the Oncology Hospital of the National
      Medical Center of the Mexican Social Security Institute. According to the
      critical sites in the surgical technique and significant for local tumor
      recurrence, we report the histological study technique followed for the
      frontolateral laryngectomy specimens. The factors to assess in the frontolateral
      laryngectomy specimen are the anterior third part of the healthy cord, the
      paraglottic space and the crico-vocal ligament. The pathologic study technique
      reported herein allows us to satisfactorily assess these risk factors.
      Macroscopic tumor excision is not sufficient, and a satisfactory histological
      analysis is required that will allow us to assess the critical sites where there
      may be residual tumor. These may translate into a higher possibility of tumor
      recurrence for the patient. Communication between pathologists and surgeons is
      essential to achieve success in this procedure.

PMID- 16283966
TI  - [Evidence-based medicine].

PMID- 16283967
TI  - [Health: who has the responsibility?].

PMID- 16283968
TI  - [Technology development].

PMID- 16283969
TI  - Aldosterone antagonists in the treatment and prevention of heart failure.
AB  - Aldosterone is elevated in heart failure and exerts multiple detrimental effects.
      In addition to playing key roles in sodium and volume regulation, aldosterone is
      involved in regulation of autonomic tone, endothelial dysfunction, tissue
      collagen turnover, myocyte fibrosis, and release of inflammatory modulators.
      Aldosterone receptor antagonists have proven to be a valuable treatment tool in
      the management of heart failure due to systolic dysfunction. Blocking the effects
      of aldosterone can improve many of the functions that are deranged in patients
      with heart failure, as well as promote excretion of sodium and water and
      preservation of potassium and hydrogen in the distal renal tubule. These
      medications can be especially effective at removing fluid from the periphery and
      soft tissues. Prevention of hypokalemia, which may predispose patients to
      arrhythmia, is an added benefit. Spironolactone and eplerenone are the two agents
      in this class that have been studied in patients with heart failure and left
      ventricular dysfunction. However, aldosterone antagonist therapy may not be
      appropriate for all patients with heart failure. Therefore, guidelines in
      managing patients on these medications should be followed to avoid serious
      electrolyte abnormalities and renal dysfunction. This review examines some of the
      mechanisms of action and the usefulness of aldosterone blockade in the management
      of heart failure.

PMID- 16283970
TI  - Calcific aortic stenosis: medical and surgical management in the elderly.
AB  - Calcific aortic stenosis is the number one indication for surgical valve
      replacement in the United States. Until recently, it was thought to be a passive
      degenerative process. However, recent retrospective studies have demonstrated
      that the risk factors for valvular disease are similar to those of vascular
      disease. Furthermore, targeting this process with medical therapy may be a future
      possibility to delay timing of valve replacement in this patient population. This
      paper reviews the current retrospective studies, experimental studies, and future
      clinical trials that will impact our understanding of this disease process and
      the future of medical therapy for these patients.

PMID- 16283972
TI  - Magnetic resonance imaging in the management of pericardial disease.
AB  - The pericardium, although seldom the primary cause of systemic illness, can be
      involved in almost every type of disease. Pericardial involvement may be subtle
      and escape detection unless specifically sought, or it can overshadow features of
      the underlying systemic disease. Suspected pericardial disease is usually
      initially evaluated with echocardiography. However, magnetic resonance imaging
      can offer additional valuable information. In addition to the excellent
      resolution and unlimited imaging planes available for visualization of the entire
      pericardial sac, the wide field of view allows for evaluation of involvement of
      adjacent cardiac structures. Dynamic functional imaging and tissue
      characterization with and without contrast can further characterize disease and
      provide information regarding concomitant myocardial disease and effects on
      cardiac motion. The treatment of specific pericardial conditions ultimately
      depends on the underlying disease process. Magnetic resonance imaging can provide
      useful information to aid in diagnosis, management, and guidance of therapy for
      pericardial disease.

PMID- 16283971
TI  - Current therapeutic strategies in cardiac amyloidosis.
AB  - Amyloidosis is a systemic disease in which clinical manifestations are caused by
      the replacement of normal tissue with insoluble amyloid fibrils. Cardiac
      involvement causes a restrictive cardiomyopathy and is associated with poor
      functional outcomes. Cardiac magnetic resonance imaging and measurement of B-type
      natriuretic peptide are particularly helpful in distinguishing restrictive
      cardiomyopathy from constrictive pericarditis, but a tissue biopsy is required to
      make the diagnosis of amyloidosis. Although standard treatment options for
      congestive heart failure may provide symptomatic relief in cardiac amyloidosis,
      prognosis remains dismal. Judicious diuretic use remains the mainstay of therapy,
      but achieving optimal fluid balance is difficult because patients are usually
      "preload dependent." Angiotensin-converting enzyme inhibitors in low doses are
      often helpful but may lead to orthostatic hypotension, particularly in patients
      who also have involvement of the autonomic nervous system. beta Blockers may be
      useful if given relatively early in the disease process, but should be used with
      caution in patients with advanced disease because they may exacerbate symptoms.
      Therapy aimed at the underlying disease process in primary systemic amyloidosis
      is based on treatment regimens used in multiple myeloma, such as melphalan and
      prednisone. These offer limited benefit when cardiac involvement is significant,
      but newer treatments, including the novel anthracycline 4'-iodo-4'
      deoxydoxorubicin, potentially combined with autologous stem cell transplantation,
      offer some hope for the future.

PMID- 16283973
TI  - Nonlipid-lowering effects of statins.
AB  - Statins have been shown to effectively reduce cardiovascular events in patients
      with hypercholesterolemia, diabetes, and coronary disease, and after an acute
      coronary syndrome in several large-scale clinical trials. Interestingly, numerous
      studies have suggested that statins exert potentially important effects
      independent of lipid lowering (ie, improve endothelial function, reduce oxidant
      stress), and have direct anti-inflammatory, antithrombotic, and plaque
      stabilizing effects. These beneficial effects may contribute to cardiovascular
      protection by statin therapy beyond low-density lipoprotein (LDL) cholesterol
      lowering. Therefore, it remains unclear at present to what extent the beneficial
      cardiovascular effects of statin treatment are dependent on LDL cholesterol
      lowering (ie, whether the same effect would be achieved by other modes of lipid
      lowering). Consequently, statins should be used as a first-line therapy for lipid
      lowering. Importantly, the observation of LDL cholesterol-independent effects of
      statins has stimulated clinical studies testing a wider use of statin treatment
      for diseases that are not thought to be related to increased LDL cholesterol
      levels, such as in patients with chronic heart failure (in particular dilated
      cardiomyopathy) and even in inflammatory diseases such as rheumatoid arthritis
      and multiple sclerosis.

PMID- 16283974
TI  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy.
AB  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a genetic
      cardiomyopathy characterized by ventricular arrhythmias and structural
      abnormalities of the right ventricle (RV). The most important aspect in the
      treatment of ARVD/C is establishing a correct diagnosis based on the
      International Task Force criteria. In our experience, cardiologists are not aware
      of these diagnostic criteria for ARVD/C and place too much importance on the
      results of magnetic resonance imaging of the RV. Patients with ARVD/C generally
      all have an abnormal 12-lead electrocardiogram, abnormal echocardiogram, and
      ventricular arrhythmias with a left bundle branch block morphology. If
      noninvasive testing suggests ARVD, invasive testing with an RV angiogram, RV
      biopsy, and electrophysiology study are recommended. We encourage patients to
      participate in the National Institutes of Health-sponsored multicenter clinical
      trial of ARVD/C (http://www.ARVD.comorhttp://www.ARVD.org). Once a diagnosis of
      ARVD/C is established, the main treatment decision involves whether to implant an
      implantable cardioverter-defibrillator (ICD). ICDs are recommended for patients
      who have experienced syncope, sudden death, or a sustained ventricular
      arrhythmia, and also for patients with overt evidence of ARVD, particularly if
      the electrophysiology study is abnormal or there is a family history of sudden
      death. We also recommend treatment of patients with ARVD/C with beta blockers and
      angiotensin-converting enzyme inhibitors, and that all patients with ARVD/C be
      screened for a mutation in the gene for plakophilin-2, because this is present in
      more than one third of patients with ARVD/C and may be helpful in the management
      of first-degree relatives.

PMID- 16283975
TI  - Percutaneous valve therapies.
AB  - Recent innovations have occurred in the treatment of valvular heart disease so
      that we now stand at the very beginning of a field that is likely to show
      considerable growth in the future. These innovations include the introduction of
      self-expanding and balloon-expandable stents containing bioprosthetic heart
      valves, and other valvular implants and techniques for the repair and treatment
      of valvular heart disease. Previously, the field of nonsurgical cardiac valve
      repair and replacement consisted solely of the use of balloon valvuloplasty for
      valvular stenosis. The ability to address aortic stenosis more definitively than
      with balloon valvuloplasty and to address regurgitant valve lesions will greatly
      expand the patients who can be treated without surgery. Percutaneous valve repair
      and replacement is at an early stage with a variety of techniques that are
      undergoing investigation. Similar to the initial development of balloon
      angioplasty for coronary artery disease, improvements in technology, techniques,
      and experience will be necessary before we can reproduce the excellent results
      achieved today with surgery.

PMID- 16283976
TI  - Pulmonary embolism: current treatment options.
AB  - The initial treatment of patients with acute pulmonary embolism has traditionally
      involved unfractionated heparin. Given the more predictable pharmacodynamic and
      pharmacokinetic properties of low molecular weight heparins, their simpler
      (fixed) dosing regimens, and few or no laboratory monitoring requirements, low
      molecular weight heparins are gradually replacing heparin for the initial
      treatment of most patients diagnosed with acute pulmonary embolism, except in
      very obese patients or patients with renal failure. Only selected patients with
      massive, life-threatening pulmonary embolism should be managed with intravenously
      administered thrombolytic drugs, surgical embolectomy, or catheter-based
      embolectomy. Likewise, inferior vena caval filter should be considered only in
      patients with an absolute contraindication to, or a documented failure of,
      anticoagulant therapy. New anticoagulants, such as ximelagatran, an oral direct
      thrombin inhibitor, or fondaparinux and idraparinux, selective factor X(a)
      inhibitors with an almost complete bioavailability after subcutaneous injection
      are promising alternatives, but these drugs have yet to find a place in the
      initial treatment of pulmonary embolism in standard day-to-day clinical practice.
      Long-term anticoagulation treatment is still provided by antivitamin K
      antagonists (eg, warfarin), which unfortunately have a narrow therapeutic window.
      Consequently, time-consuming monitoring is required to ensure the therapeutic
      anticoagulant effect. A target International Normalized Ratio (INR) of 2.5 (INR
      range: 2.0 to 3.0) is recommended for warfarin therapy. This treatment should be
      continued for at least 3 months for patients with a first episode of pulmonary
      embolism secondary to a transient (reversible) risk factor, or up to 6 to 12
      months for patients with a first episode of idiopathic pulmonary embolism.

PMID- 16283977
TI  - Nontransplant surgical alternatives for heart failure.
AB  - Heart failure is a tremendous burden on society, and on the health care system in
      particular. Historically, medical treatments have been the only therapies
      available because patients were felt to be too high risk to undergo conventional
      cardiac surgical procedures. Cardiac transplantation remains an established
      therapy for certain patients with end-stage heart failure but it is limited by
      donor availability and the need for lifelong immunosuppression. Recent advances
      in myocardial protection, operative techniques, and perioperative care have made
      it possible for conventional surgery, such as coronary bypass, ventricular
      reconstruction, and valve repair, to be offered to many patients with advanced
      heart failure with good short- and long-term results. In 2005, few patients are
      inoperable.

PMID- 16283978
TI  - Minimally invasive saphenous vein harvesting using a laryngoscope: procedural,
      functional, and morphologic evaluation.
AB  - BACKGROUND: Because commercial minimally invasive harvesting equipments
      significantly increase operation costs, they are not always available in all
      clinics worldwide. The aim of this study was to investigate whether minimally
      invasive saphenous vein harvesting using a laryngoscope can be applied
      efficiently and successfully. METHODS: Thirty patients were prospectively
      randomized into two groups. One group underwent a minimally invasive technique
      using a laryngoscope; the other, open saphenous vein harvest. A modified bridging
      technique, in which tissue retraction and illumination is achieved with a
      sterilized laryngoscope, was used for minimally invasive harvesting. Smooth
      muscle contractile and endothelial functions were tested in vitro using an organ
      chamber. Morphology was examined with light microscopy. RESULTS: There was no
      statistically significant difference in harvest times or length of the vein
      harvested by either of the above mentioned techniques. Total length of the
      incision in the minimally invasive group was significantly shorter than that in
      the open group. In follow-ups, no significant complications occurred in either
      group. Pain and leg edema were significantly less in the minimally invasive group
      compared to those of the open group. There was no significant difference in
      response to acetylcholine and 80 mM KCl between veins taken with the laryngoscope
      compared to veins taken with the traditional open technique. Similarly,
      histological data was unable to show any significant damage to the vessel wall.
      CONCLUSIONS: Because the laryngoscopic saphenectomy does not harm the harvested
      graft, it can be applied, instead of other minimally invasive saphenous vein
      harvesting systems, with a zero cost, efficiently, successfully, and with
      satisfactory speed and significant reduction of postoperative leg pain and wound
      complications.

PMID- 16283979
TI  - Inflammatory aneurysm of the descending aorta: a case report.
AB  - We report a rare case of an inflammatory descending aneurysm. At surgery, the
      patient had multiple aneurysms on the descending aorta. Histology of the specimen
      demonstrated an infiltration of chronic inflammatory cells in the aortic media.

PMID- 16283980
TI  - Embolic activity subsequent to injection of the internal mammary artery with
      papaverine hydrochloride.
AB  - BACKGROUND: Neurologic injury is a rare yet devastating outcome of coronary
      artery bypass grafting surgery. Mechanisms producing both focal and global
      neurologic injuries include embolization, cerebral hypoperfusion, and
      hypotension. In this present study, we report an association between variations
      in the treatment of the internal mammary artery with the detection of cerebral
      embolic signals. METHODS: An intensive intraoperative neurologic and physiologic
      monitoring approach was implemented to associate discrete processes of clinical
      care with the concurrent detection of cerebral embolic signals, cerebral
      hypoperfusion, and hypotension. The method of treating the left internal mammary
      artery was tracked among 68 patients undergoing isolated coronary artery bypass
      grafting. Cerebral embolic signals were counted within 3 minutes of the treatment
      of the left internal mammary artery. RESULTS: Among a series of 68 patients
      undergoing isolated coronary artery bypass grafting, 22 were not treated with
      papaverine. Of those treated, 12 received injection intraluminally and 28 had a
      topical application. Embolic signals were noted concurrently among 7 patients
      receiving injection of papaverine. No embolic signals were noted among patients
      who were treated topically. CONCLUSIONS: We report an association between the
      injection of papaverine hydrochloride and cerebral embolic signals. Our findings
      suggest that adoption of topical applications of papaverine hydrochloride may
      offer opportunities to reduce a portion of cerebral embolic signals in the
      setting of coronary artery bypass grafting.

PMID- 16283981
TI  - Less invasive radial artery harvesting: two years' experience.
AB  - BACKGROUND: For coronary surgery we often use the radial artery (RA) instead of
      the saphenous vein, trying to exploit the advantages offered by this conduit. To
      eliminate the problems regarding alteration of upper-extremity function after RA
      procurement related to the standard conventional harvesting technique, we started
      using the less invasive harvesting technique with surprisingly good preliminary
      results. To compare the outcomes of open versus less invasive harvesting
      procedures, a prospective, nonrandomized study was developed by 2 centers.
      METHODS: From January 2001 to March 2003, there were 87 consecutive patients in
      the less invasive radial artery harvesting (LIRAH) group and 90 patients in the
      conventional radial artery harvesting (CRAH) group. Patient characteristics and
      demographics were similar in the groups. Data collection was made to evaluate
      possible benefits of the LIRAH technique in terms of fewer forearm and hand
      complications, better aesthetics, and improved patient satisfaction. RESULTS:
      Between January 11, 2001, and March 30, 2003, 177 patients underwent either
      primary or redo coronary artery revascularizations with procurement of the RA for
      use as a conduit with the less invasive harvesting technique. The mean follow-up
      was 2 months. Four patients died, and overall mortality was 2.26%. One hundred
      seventy-three patients were successfully examined during the first postoperative
      control, 85 in the LIRAH group and 88 patients in the CRAH group. Objective and
      subjective data were collected from the consultant. The overall average age was
      60.5 years (range, 40-77 years). In the LIRAH group, the mean overall incision
      length (when 2 incisions were necessary, both incision lengths were measured) was
      5.6 cm (range, 4-10 cm), and the mean vessel length was 16 cm (range, 10-19 cm).
      Eighteen patients (20.6%) necessitated double incision. Mean harvesting time
      (from incision to skin closure) was 43.3 min (range, 25-70 min). Fourteen
      patients (16.4%) presented some kind of complication during the study. There were
      no cases with acute ischemia, bleeding, or re-exploration. Seventy-five patients
      (88.2%) found the cosmetic result excellent. Ten patients (11.8%) found it good,
      and none considered it mediocre. In the CRAH group, the mean incision length was
      20 cm (range, 18-22 cm), and the mean vessel length was 18 cm (range, 17-20 cm ).
      Mean harvesting time (from incision to skin closure) was 30.8 min (range, 14-45
      min). Thirty-four patients (38.6%) presented some kind of complication during the
      study. Three patients (3.5%) found the cosmetic result excellent. Forty-three
      (48.8%) found it good, and 42 (47.7%) considered it mediocre. CONCLUSIONS: A
      potential of fewer neurological forearm postoperative complications, better
      aesthetics, and improved patient satisfaction can be achieved by the LIRAH
      technique.

PMID- 16283982
TI  - Clampless anastomosis: novel device for clampless proximal vein anastomosis in
      OPCAB surgery--the initial Spyder experience.
AB  - The Spyder is a novel device that enables the attachment of a vein to the aorta
      by compliant, interrupted anastomosis; this minimizes aortic manipulation during
      off pump-coronary artery bypass (OPCAB) surgery. Its use may reduce transcranial
      Doppler signals recorded during CABG. We performed 250 anastomoses in 160 OPCAB
      cases in many centers and recorded efficiency and efficacy data. There were no
      adverse events noted during the operative period. In a subset of patients in one
      center, flow (n = 48) and transcranial Doppler signals (n = 22) were measured. We
      found the device to be a useful adjunct for minimally invasive CABG surgery.

PMID- 16283983
TI  - Stuck bioprosthetic aortic valve--a new entity? A case report.
AB  - We describe herein a case of bioprosthetic valve malfunction, which closely
      imitates a stuck valve. Although the term "stuck" was used originally for the
      immovable mechanical valve leaflets, the echocardiographic manifestation of this
      malfunction is similar to those of a mechanical one. The clinical presentation of
      the stuck bioprosthesis is, however, far more benign than a stuck mechanical
      valve. Familiarity with this entity is important.

PMID- 16283984
TI  - Division of the brachioradialis muscle: a modification of the current technique
      in endoscopic radial artery harvesting.
AB  - BACKGROUND: Utilization of the radial artery as a conduit for coronary artery
      bypass grafting has increased significantly over the past 8 years. Concurrently,
      minimally invasive surgical techniques have been increasingly applied resulting
      in improved aesthetics, less pain, and decreased morbidity and length of hospital
      stay. Endoscopic radial artery harvesting (ERAH) has been shown to be of benefit
      to patients undergoing coronary artery bypass grafting. The brachioradialis is a
      recognized limitation in ERAH. To date, the standard operative techniques for
      ERAH have included maintaining the integrity of the brachioradialis muscle.
      Objective. The aim of this study was to assess the effect of dividing the medial
      border of the brachioradialis muscle during ERAH. METHODS: We performed ERAH on 9
      cadaveric arms using standard endoscopic vein harvesting equipment (30-degree/5
      mm endoscope, subcutaneous retractor, and pig-tail vessel dissector) and
      ultrasonic harmonic coagulating shears. In 5 cadaveric arms, the medial aspect of
      the brachioradialis muscle was preserved during the dissection. In 4 arms, the
      medial border of the brachioradialis muscle was divided. All 9 harvests were
      timed and compared. At the completion of the endoscopic dissection, all 9 arms
      were opened and examined for neurovascular injury. RESULTS: In cadaveric arms,
      modifying the current ERAH technique by dividing the medial border of the
      brachioradialis muscle resulted in a visible increase in tunnel size. In the
      group where the brachioradialis muscle was divided, a statistically significant
      reduction in harvest time of 32% was observed (P = .02). Post-harvest examination
      revealed no gross neurovascular injury; specifically, no injuries to the
      superficial branches of the radial nerve or the lateral antebrachial cutaneous
      nerves were identified. CONCLUSION: Division of the medial border of the
      brachioradialis muscle during endoscopic radial artery harvesting appears to be a
      safe technique modification that subjectively improves working space and vision
      of vital structures, facilitating ease of the procedure. Objectively, division of
      the medial border of the brachioradialis muscle resulted in a statistically
      significant reduction in harvest time in cadaveric arms when compared with the
      current technique of ERAH. A clinical pilot study to verify the efficacy and
      safety of this technique modification is warranted.

PMID- 16283985
TI  - Subnormalization of left ventricular shape after successful coronary
      revascularization.
AB  - BACKGROUND: It is asumed that the shape and size of the left ventricle could
      change after successful revascularization and that the shape and size reflect
      left ventricular function. METHODS: Echocardiography and Simpson's rule were used
      for evaluating the endocardial surface area of the left ventricle and elongation
      of the left ventricle as shape index in 13 patients before coronary arterio
      venous bypass grafting (CABG) and 1 year after successful CABG. RESULTS: After
      successful CABG, the left ventricle becomes bigger and less elongated than before
      CABG. Results show a change from concentric hypertrophy of the left ventricle
      before CABG to subnormalization after CABG. DISCUSSION: We suppose that the
      subnormalization of left ventricular size and shape is the result of successful
      CABG and successful rehabilitation. The change of left ventricular size and shape
      after CABG might depend more on the original state of the left ventricle before
      surgery.

PMID- 16283987
TI  - Modelling the natural history of geographic atrophy in patients with age-related
      macular degeneration.
AB  - PURPOSE: To model the natural course of geographic atrophy (GA) in patients with
      age-related macular degeneration (AMD). METHODS: Data on the natural course of GA
      were collected in the multi-center, longitudinal, prospective observational FAM
      study. The size of GA was measured by autofluorescence scanning laser
      ophthalmoscopy. The natural course of GA is modelled by two different mixed
      effect models (MEM). Both models are compared with respect to the correctness of
      the model assumptions, goodness of fit, and predictive behavior. RESULTS: The
      linear model results in better prediction, the non-linear model is more in
      agreement with the model assumptions. The non-linear model fits the data for
      small and large areas of GA better, while the linear model seems to be more
      adequate for the medial areas. More data will be needed to study the interplay of
      both models in more detail. CONCLUSIONS: The natural course of GA varies
      extremely between individuals. However, reliable factors for the explanation of
      this variability have so far not been established. MEM are useful for describing
      "inter-individual" as well as "intra-individual" influences without the need for
      precise knowledge of the influencing factors. Using MEM to evaluate data on the
      natural history of GA allows one to derive parameter estimates, which could be
      used to design interventional trials for modes of therapy with a potential to
      reduce or stop the progression of GA in patients with AMD.

PMID- 16283988
TI  - Prevalence of glaucoma in the wroclaw population. The wroclaw epidemiological
      study.
AB  - PURPOSE: Primarily to determine the prevalence of various types of glaucoma and
      ocular hypertension in Wroclaw inhabitants aged 40-79 years. The second aim of
      the study was to determine the number of undiagnosed glaucoma cases in this
      population. METHODS: A representative group of the Wroclaw population (4853
      people aged from 40 to 79 years) was recruited by a proportional simple random
      sampling selection with stratification. All participants underwent the first,
      screening-stage examination, which included a medical history interview,
      intraocular pressure (IOP) measurement, anterior chamber depth assessment by the
      Van Herrick technique, and optic nerve head (ONH) assessment by means of indirect
      ophthalmoscopy (Volk's lens), confocal scanning laser ophthalmoscopy with a
      Heidelberg Retinal Tomograph (HRT) and scanning laser polarimetry by the GDx
      Nerve Fiber Analyzer (GDx). The second stage, in glaucoma-suspect patients only,
      included best corrected visual acuity, static perimetry, 24-hour monitoring of
      IOP, gonioscopy, and full eye examination with mydriasis. Glaucoma was diagnosed
      by the presence of any two of the following: characteristic morphological changes
      in the optic disc, glaucomatous visual field abnormalities, and intraocular
      pressure greater than 21 mmHg. RESULTS: The overall prevalence of glaucoma was
      1.6% (79 subjects). The prevalence increased with age from 0.4% in subjects
      belonging to the age group 40-49 years to 4.6% in people aged between 70 and 79
      years. The prevalence of definite primary open-angle glaucoma was 1.0% (49
      subjects). Normal-pressure glaucoma was diagnosed in 13 subjects (0.3%). Ocular
      hypertension was diagnosed in 92 subjects (1.9%). CONCLUSION: The prevalence of
      the different types of glaucoma was similar to that found in other white
      populations. Among the subjects examined, 79 had various forms of glaucoma and
      71% of them had not previously been diagnosed. Undiagnosed glaucoma is a serious
      public health problem in Poland.

PMID- 16283989
TI  - Astigmatism and its determinants in the Tehran population: the Tehran eye study.
AB  - PURPOSE: To determine the prevalence of astigmatism and its epidemiological risk
      factors in Tehran via a population-based study. METHODS: By means of a stratified
      random cluster sampling, 6497 citizens representing a cross-section of the
      population of Tehran were selected from 160 clusters. Eligible people were
      recruited through a door-to-door household survey in the selected clusters and
      transferred to a clinic for an extensive eye examination and interview. The
      refractive status was determined with manifest refraction. Astigmatism was
      defined as cylinder worse than or equal to 0.5 D. High astigmatism was defined as
      a manifest cylinder > or =1.5 D. RESULTS: Between August and December 2002, 4565
      of the 6497 eligible individuals in the sample attended the interview and
      ophthalmic examination (a participation rate of 70.3%). The age- and gender
      standardized prevalence of astigmatism was 50.2% (95% CI, 48.4% to 51.9%) on
      manifest refraction. High astigmatism was found in 490 right eyes (11.1%; 95% CI,
      10.1% to 12.0%). Of 2532 participants with ametropia, 59.6 (95% CI, 57.6-61.5)
      had astigmatism. The percentages of with-the-rule, against-the-rule and oblique
      astigmatism were 33.6%, 36.9% and 29.3%, respectively. The proportion of type of
      astigmatism was significantly related to age (p < 0.001). The univariable
      analysis of astigmatism between family members yielded odds ratios of 1.47 (95%
      CI, 1.14 to 1.89, p = 0.003) for the association of astigmatism among siblings.
      After controlling for age, refractive errors and education, the pairwise sibling
      association remained statistically significant (OR 1.43, 95% CI, 1.08 to 1.88).
      CONCLUSION: These findings revealed a high prevalence of astigmatism in the
      population. Age, education and ametropia were the main predictors of astigmatism
      in Tehran. Our findings should be considered for case finding and astigmatism
      correction programs. Our data confirmed a modest familial aggregation for
      astigmatism.

PMID- 16283990
TI  - Methodology and recruitment of probands and their families for the Genes in
      Myopia (GEM) Study.
AB  - PURPOSE: Myopia is considered to be a complex disease involving both
      environmental and genetic factors. The Genes in Myopia (GEM) Study aims to
      recruit probands with myopia and their family members to allow genetic analysis
      of myopia to be undertaken. The purpose of this paper is to describe the
      methodology and recruitment of probands and families for the GEM Study. METHODS:
      In a sample-based prospective study, 2,095 probands with myopia of -0.50 DS or
      worse and a positive family history of myopia were contacted via the Melbourne
      Excimer Laser Group (MELG) database. Probands and family members recruited into
      the study undertook a detailed assessment including questionnaire, best-corrected
      visual acuity, objective and subjective refraction, axial length, anterior
      chamber depth, keratometry readings, slit-lamp examination, height, weight and
      head circumference measurements, and blood sample collection for DNA analysis.
      RESULTS: 280 probands with myopia have been recruited into the GEM Study.
      Probands had a mean age of 49.33 yrs. (SD +/- 11.64) with the average age of
      myopia onset being 12.58 years (SD +/- 6.71). The average spherical-component
      refractive error was: right eye -5.13 DS (SD +/- 3.06) and left eye -5.14 DS (SD
      +/- 3.16). Probands with extreme myopia (-10 DS or worse) showed the highest
      study participation rate of 56%, when compared to high (-5 DS < -10 DS) (20%),
      moderate (-3 DS < - 5 DS) (18%) and low myopia (-0.5 DS < -3 DS) (10%). A total
      of 279 out of 505 (55%) additional family members recruited were also found to be
      myopic. CONCLUSIONS: The GEM study has used a targeted approach to identify an
      Australian cohort with a diverse spread of myopia, ranging from low to extreme.
      Recruitment of probands via the use of an excimer laser practice has proved to be
      an efficient and economic means of identifying probands with a family history of
      myopia. In addition, the participation rate in the study appears to vary
      reflecting a proband's perception of disease severity.

PMID- 16283991
TI  - How high is the non-response rate of patients referred for eye examination from
      diabetic screening camps?
AB  - AIM: To elucidate the rate of non-response among diabetics (recently diagnosed in
      rural diabetic screening camps) who were referred for eye examination to detect
      diabetic retinopathy. METHODS: At diabetic retinopathy screening camps, all
      patients underwent dilated fundus examination using binocular indirect
      ophthalmoscopy. RESULTS: Of the 4,111 known diabetics, only 2231(55%) patients
      attended the diabetic retinopathy screening camps. Likewise, of the 1076 newly
      detected diabetics, only 125 (11.6%) attended the diabetic retinopathy screening
      camps. CONCLUSIONS: Non-response of such a magnitude calls for creating greater
      awareness among masses on diabetes and its microvascular complications. Second,
      conducting simultaneous diabetes screening and diabetic retinopathy screening
      camps could minimize the dropout rate.

PMID- 16283995
TI  - Stigma: barrier to mental health care among ethnic minorities.
AB  - This paper explicates the stigma of mental illness as it is experienced by four
      ethnic minority groups in the United States. Concerns about prejudice and
      discrimination among individuals who suffer burdens related to mental illness are
      delineated. It is proposed that ethnic minority groups, who already confront
      prejudice and discrimination because of their group affiliation, suffer double
      stigma when faced with the burdens of mental illness. The potency of the stigma
      of mental illness is one reason why some ethnic minority group members who would
      benefit from mental health services elect not to seek or adequately participate
      in treatment. The combination of stigma and membership in an ethnic minority
      group can impede treatment and well-being, creating preventable and treatable
      mortalities and morbidities. The article concludes with recommendations for
      research and health policy implications.

PMID- 16283996
TI  - Stigma of mental illness among American Indian and Alaska Native nations:
      historical and contemporary perspectives.
AB  - Among American Indian and Alaska Native (AIAN) people, the concept of mental
      illness has different meanings and is interpreted in various ways. This paper
      describes the realities of mental health care that confront AIAN people. Stigma
      is associated with mental illness, which can be a barrier for those individuals
      who are in need of mental health services. Within the context of the AIAN
      historical and contemporary experiences, the paper details domains that
      negatively influence the lives of AIAN people. Included are the failure of the
      U.S. government to fulfill its treaty agreements with AIAN people; the
      disparities in income and education, and the pervasiveness of poverty; and access
      to care issues. These domains help to set the stage for health disparities that
      frequently catapult AIAN people to early morbidity and mortality. Importantly,
      many of these conditions are preventable. The paper concludes with
      recommendations for a more diverse workforce that will include AIAN mental health
      professionals who are available to provide culturally competent care to AIAN
      people in a variety of settings.

PMID- 16283997
TI  - Stigmatization of Hispanic children, pre-adolescents, and adolescents with mental
      illness: exploration using a national database.
AB  - This paper examines descriptive statistics for the primary payer, length of stay,
      and admission source of an acute care hospitalization of Hispanic children--pre
      adolescents, and adolescents with a primary psychiatric Diagnostic Related Group
      (DRG)--and relates these variables to the concept of stigma. This paper was a
      secondary analysis that used data from the National Inpatient Sample database.
      Psychosis was the most frequent diagnosis of Hispanic youth who were
      hospitalized. More Hispanic pre-adolescents had a psychiatric DRG than any other
      ethnic group but fewer Hispanic adolescents were diagnosed with a psychiatric DRG
      than any other ethnic group. For Hispanic pre-adolescents and adolescents, the
      primary payer was Medicaid versus private insurance for White pre-adolescents and
      adolescents. The length of stay was approximately the same for all ethnic groups.
      The admission source differed for Hispanic pre-adolescents and adolescents with
      the majority of pre-adolescents being admitted routinely and the majority of
      Hispanic adolescents being admitted through emergency departments.
      Recommendations are made for future research, clinical practice, and public
      policy related to the stigmatization of Hispanic children and adolescents with
      mental illness.

PMID- 16283998
TI  - Length of stay, admission types, psychiatric diagnoses, and the implications of
      stigma in African Americans in the nationwide inpatient sample.
AB  - African Americans purportedly have a higher prevalence of mental illnesses but
      are often misdiagnosed and less likely to seek treatment. Delayed treatment has
      been associated with the stigma related to these disorders. The demographic
      characteristics, length of stay, most prevalent psychiatric diagnoses, and
      hospital admissions of African Americans were compared to other U.S. populations
      using a nationwide sample (N = 4,474,732). African American participants were
      younger, had significantly longer lengths of stay, and were admitted more often
      through the emergency room than the other groups in this sample. Psychosis,
      alcohol/drug dependence, and depressive neurosis were the most prevalent
      psychiatric diagnoses reported for African American participants. Research is
      needed to explain these results so that strategies can be instituted to improve
      the poor mental health outcomes often observed in African American populations.

PMID- 16283999
TI  - Mental illness and principal physical diagnoses among Asian American and Pacific
      Islander users of emergency services.
AB  - The stigma of mental illness is one of the factors that prevents Asian
      Americans/Pacific Islanders (APIs) from seeking formal mental health services. A
      somatic complaint is more acceptable in expressing psychiatric/emotional
      distress. Admission diagnoses in API emergency service users with secondary
      psychiatric diagnoses were identified from the 2001 National Inpatient Sample
      (NIS) of the Healthcare Cost and Utilization Project (HCUP). The sample consisted
      of 10,623 adult APIs. The study examined the differences in the six leading
      principal physical admission diagnoses between API emergency service users with
      psychiatric diagnoses and those without psychiatric diagnoses. Several of the
      study findings create concern (e.g., the higher percentage of APIs with
      psychiatric diagnosis who were discharged against medical advice, the high
      percentage admitted with medication intoxication). Further study is needed to
      provide guidance for clinical practice.

PMID- 16284000
TI  - Sickle cell disease: a stigmatizing condition that may lead to depression.
AB  - Individuals with a chronic illness such as sickle cell disease are at risk for
      depression. Moreover, they are at risk for untreated depression. Depression may
      go untreated because of the stigma and high rates of disability associated with
      this chronic illness that most often affects African Americans in the United
      States. The purpose of this cross-sectional study was to describe depressive
      symptoms using the Beck Depression Inventory Fast Screen in a sample of 232
      African American adults with sickle cell disease. Respondents reported higher
      levels of depression (26%) and depressive symptoms (32%) than did the overall
      United States population (9.5%). All adults with chronic illnesses need to be
      screened for depression in primary care practice sites where the diagnosis and
      treatment of depression needs to be coordinated.

PMID- 16284001
TI  - Stigmatization in Alzheimer's disease research on African American elders.
AB  - Stigmatization in research sustains the spread of the silent epidemic of
      Alzheimer's disease (AD) in African American populations. Researchers use
      stereotypes and inappropriate assumptions to select a paradigm to examine the
      symptoms of AD. This paradigm fails to encompass the symptoms as manifested by
      African American elders. Yet, stigmatization can be minimized by recognizing the
      genetic heterogeneity of the symptoms within the general population, especially
      those manifested by African American elders. Thus, researchers can utilize
      pioneering genetic analyses to identify other paradigms critical in the
      assessment and proactive treatment of the symptoms of AD needed for this
      vulnerable population.

PMID- 16284002
TI  - Noninvasive characterization of myocardial blood flow in diabetic, hypertensive,
      and diabetic-hypertensive rats using spin-labeling MRI.
AB  - OBJECTIVE: Microvascular alterations in the diabetic and hypertensive heart are
      likely to contribute to heart failure. In this work, myocardial blood flow and
      left ventricular function were measured in vivo in diabetic, hypertensive, and
      diabetic-hypertensive rats using MRI methods. METHODS: An 8-week-duration type 1
      diabetes was induced by streptozotocin (STZ) in 8 Wistar-Kyoto (WKY) rats (STZ)
      and in 11 spontaneously hypertensive (SHR) rats (STZ-SHR). Fourteen WKY and 12
      SHR served as control and hypertensive groups. Myocardial blood flow
      quantification was performed using an arterial spin-labeling MRI method. Left
      ventricular morphology and function were assessed during the same experiment
      using cine-MRI. RESULTS: Respective myocardial blood flow values for each group
      were 6.4 +/- 1.1 (WKY), 6.0 +/- 1.9 (STZ), 5.5 +/- 1.3 (SHR), and 4.3 +/- 0.9 mL.
      g(-1). min(-1) (STZ-SHR). Myocardial blood flow was significantly decreased in
      STZ-SHR rats compared with the other groups (p <.05, STZ-SHR vs. all groups).
      Cine-MRI showed morphological alterations in all pathological groups. No
      alteration of the ejection fraction was observed in the pathological groups.
      CONCLUSION: Myocardial blood flow is altered in vivo before any sign of heart
      failure when rats have type 1 diabetes and hypertension simultaneously. When only
      one of the pathologies occurs, MBF does not vary significantly.

PMID- 16284003
TI  - Protective effects of ischemic preconditioning on the intestinal mucosal
      microcirculation following ischemia-reperfusion of the intestine.
AB  - OBJECTIVE: The small bowel villi are extremely sensitive to ischemia-reperfusion
      (IR) injury and a range of microcirculatory disturbances contribute to structural
      and functional changes. The aim of this study was to determine the protective
      effects of ischemic preconditioning (IPC) of the intestine on the mucosal villous
      microcirculation during IR injury of the intestine and whether heme oxygenase
      (HO) is involved in the protection. METHODS: Rats were allocated into 4 groups:
      (1) sham, (2) IR consisting of 30 min of ischemia followed by 2 h of reperfusion,
      (3) IPC, as in IR group, but preceded by 10 min of ischemia and 10 min of
      reperfusion, and (4) with administration of zinc protoporphyrin, an HO inhibitor
      before IPC and IR. The mucosa of an exteriorized segment of ileum was visualized.
      Mucosal perfusion index (MPI), red blood cell (RBC) velocity and leukocyte
      endothelial interactions during reperfusion were assessed continuously using in
      vivo fluorescence microscopy. HO activity in the ileum was assessed at the end of
      the reperfusion period. RESULTS: IPC improved the MPI by 26% and the RBC velocity
      by 29% on comparison to IR. IR led to a 52% increase in leukocyte-endothelial
      interactions on comparison to IPC. The administration of zinc protoporphyrin
      reversed the beneficial effects of IPC. There was a two fold increase of HO
      activity in IPC compared to IR, whereas zinc protoporphyrin significantly reduced
      the HO activity. CONCLUSIONS: IPC conferred a protective effect on the villous
      microcirculation possibly via HO and might prove to be an effective strategy for
      the amelioration of IR injury.

PMID- 16284004
TI  - Localization of the renin-angiotensin system components to the skeletal muscle
      microcirculation.
AB  - OBJECTIVES: Local renin-angiotensin systems have been found in various organs and
      tissues throughout the body. The studies described here tested the hypothesis
      that a fully functional renin-angiotensin system exists in the skeletal muscle
      microvasculature. The purpose of this study was to localize the components and
      products of the system to the skeletal muscle microvasculature. METHODS: The
      presence of mRNA and protein for renin and angiotensinogen was shown by reverse
      transcriptase polymerase chain reaction analysis and immunohistochemistry,
      respectively. Angiotensin II concentration in isolated microvessels was measured
      by high-performance liquid chromatography separation and radioimmunoassay.
      RESULTS: Renin and angiotensinogen mRNA was detected from isolated cremaster
      microvessels. Specific staining for renin and angiotensinogen protein was found
      throughout the walls of microvessels. The concentration of the angiotensin II in
      the microvessels (104.3 +/- 18.1 fmol/g) was found to be higher than the
      concentration of angiotensin II in the plasma (8.7 +/- 1.2 fmol/mL) of the same
      animals. Also, it was shown that the microvessel angiotensin II concentrations in
      spontaneously hypertensive rats were higher than in Sprague-Dawley rats.
      CONCLUSIONS: The current study demonstrates that within the skeletal muscle
      microvessels, the components and products necessary for a local renin-angiotensin
      system are present, but does not rule out the possibility of interaction between
      circulating and tissue renin-angiotensin systems.

PMID- 16284011
TI  - Health care reform: why? What? When?
AB  - Dissatisfaction with the U.S. health care system is widespread, but no consensus
      has emerged as to how to reform it. The principal methods of finance-employer
      based insurance, means-tested insurance, and Medicare-are deeply and irreparably
      flawed. Policymakers confront two fundamental questions: Should reform be
      incremental or comprehensive? And should priority be given to reforming the
      financing system or to improving organization and delivery? We consider here
      several proposals for incremental reform and three for comprehensive reform:
      individual mandates with subsidies, single payer, and universal vouchers. Over
      the long term, reform is likely to come in response to a major war, depression,
      or large-scale civil unrest.

PMID- 16284005
TI  - Mitogen-activated protein kinases regulate platelet-activating factor-induced
      hyperpermeability.
AB  - OBJECTIVE: The authors tested the hypothesis that p42/44- (ERK-1/2) and/or p38
      mitogen-activated protein kinases (MAPK) are in vivo regulatory elements in the
      platelet-activating factor (PAF) activated signaling cascade that stimulates
      microvascular hyperpermeability. METHODS: FITC-dextran 70 was used as the
      macromolecular tracer for microvascular permeability in the mouse mesenteric fat
      tissue. Interstitial integrated optical intensity (IOI) was used as an index of
      permeability. RESULTS: An application of 10(-7) M PAF increased IOI from 23.1 +/-
      3.6 to 70.8 +/- 7.4 (mean +/- SEM). Inhibition of ERK-1/2 with 3 microM and 30
      microM AG126 reduced IOI to 32.3 +/- 2.5. Similarly, inhibition of p38-MAPK with
      6 nM, 60 nM and 600 nM SB203580 lowered IOI to 29.1 +/- 2.4. CONCLUSIONS: The
      results demonstrate that ERK-1/2 and p38MAPK participate in the signaling cascade
      that regulates PAF-induced microvascular hyperpermeability in vivo.

PMID- 16284012
TI  - Whence and whither health insurance? A revisionist history.
AB  - Throughout the postwar era in federal health policy, policymakers have sought to
      expand both public and private insurance coverage, while wrestling with the cost
      consequences of the demand generated by the insurance-financing mechanisms thus
      created. This essay advances the view that the limits to insurance expansion have
      been reached and that public and private plan sponsors will henceforth
      continually "thin out" the coverage they offer. In this environment, policymakers
      seeking to mitigate access concerns may need to consider strategies that promote
      direct service delivery. This emerging regime, it is argued, will have important
      implications for the future of innovation in health care.

PMID- 16284013
TI  - The political divide in health care: a liberal perspective.
AB  - U.S. health policy has been consumed by an ideological divide between
      conservative and liberal viewpoints. The liberal philosophy, based on both moral
      principles and utilitarian arguments, attempts to balance the needs of the
      individual with the concerns of the entire population. Elements of the liberal
      health care perspective include a belief that health care is an equal right of
      all people, the implementation of that right through a social insurance system
      that provides universal health coverage, equitable financing of health care, and
      a commitment to equality in health care.

PMID- 16284014
TI  - The rise in health care spending and what to do about it.
AB  - Reforms for slowing the growth in health care spending and increasing the value
      of care have largely focused on insurance-based solutions. Consumer-driven health
      care represents the most recent example of this approach. However, much of the
      growth in health care spending over the past twenty years is linked to modifiable
      population risk factors such as obesity and stress. Rising disease prevalence and
      new medical treatments account for nearly two-thirds of the rise in spending. To
      be effective, reforms should focus on health promotion, public health
      interventions, and the cost-effective use of medical care.

PMID- 16284016
TI  - Making markets work: five steps to a better health care system.
AB  - Although the U.S. health care system has made remarkable advancements, it is
      costly and wasteful, and it leaves many people without appropriate care. The
      challenge for public policy is to enable consumers and taxpayers to obtain good
      value for their health care dollars. Achieving this objective stands the greatest
      chance of success if health care markets function well. To make markets work, we
      recommend changes in five areas of public policy: tax reform, insurance reform,
      improved provision of information, enhanced competition, and malpractice reform.
      Our policy reforms will improve the productivity of the health care system, make
      insurance more affordable, reduce rates of uninsurance, and increase tax fairness
      and progressivity.

PMID- 16284017
TI  - Federalism and health policy.
AB  - This paper presents a cyclical theory of U.S. federalism and social policy: Many
      social policy initiatives are tested and refined at the state level, especially
      during conservative periods, and later morph into national policies. The paper
      describes such federalism cycles and offers an interpretation of why and how they
      occur, focusing on Medicaid. State activism has preserved and expanded Medicaid
      through policy innovation and resistance to retrenchment, especially in
      conservative periods, by taking advantage of the flexibility the program
      provides. I conclude that Medicaid's incremental/partnership approach is
      appropriate and feasible to build on for a future expansion of health care
      coverage.

PMID- 16284018
TI  - Health insurance in Mexico: achieving universal coverage through structural
      reform.
AB  - Fairness in finance is an intrinsic and challenging goal of health systems.
      Mexico recently devised a structural reform that responds to this challenge.
      Through a new system of social protection in health that will offer public
      insurance to all citizens, the reform is expected to reduce catastrophic and out
      of-pocket spending while promoting efficiency, more equitable resource
      distribution, and better-quality care. This paper analyzes the reform, focusing
      on financial features, expected benefits, and future challenges. It also
      highlights aspects of relevance for other countries that are striving to
      formulate and implement health policies to promote universal social protection
      and fair financing.

PMID- 16284020
TI  - Managed consumerism in health care.
AB  - The future of market-oriented health policy and practice lies in "managed
      consumerism," a blend of the patient-centric focus of consumer-driven health care
      and the provider-centric focus of managed competition. The optimal locus of
      incentives will vary among health services according to the nature of the
      illness, the clinical technology, and the extent of discretion in utilization. A
      competitive market will manifest a variety of comprehensive and limited benefit
      designs, broad and narrow contractual networks, and single-and multispecialty
      provider organizations.

PMID- 16284021
TI  - Reviving managed care with health savings accounts.
AB  - Although health savings accounts (HSAs) and managed care are often seen as
      antithetical, they can be integrated in fruitful ways. Moreover, combining these
      approaches would serve policy objectives by clarifying the payment
      responsibilities of patients, health plans, and premium payers, thus altering
      important perceptions about health care decision making. The availability in HSAs
      of funds that patients can use to pay for services not covered under insurance
      contracts should help to relegitimize the predetermination of benefits and enable
      the public and the legal system to take a more benign view of corporate health
      plans as agents of their subscribers.

PMID- 16284022
TI  - Coordinated agency versus autonomous consumers in health services markets.
AB  - Despite widespread acceptance of the competitive market model in the U.S. health
      care system, debate continues regarding the optimal form of competition and the
      patient-professional relationship. The managed care model envisions organizations
      that act as the consumer's agent, addressing the challenges that consumers face
      in the market for health care services. The consumer-directed health plan model
      envisions autonomous, well-informed, price-conscious consumers shopping among
      providers unconstrained by organizational affiliations. Although advocates of
      these two approaches stress their philosophical differences, the realities of the
      market suggest that both models, as well as hybrids, might be valued by
      consumers.

PMID- 16284023
TI  - Competition in health care: its evolution over the past decade.
AB  - Understanding the roller-coaster experience with the use of market forces in
      health care over the past ten years provides important context for discussions of
      likely future developments in the nature of competition. The period began with
      acceptance of managed care transforming the organization of medical care delivery
      and proceeded to a period in which many of the changes were reversed. The vision
      of integrated delivery has now been replaced with a vision of a more active role
      for consumers. But the greatest potential for a larger role for consumers lies in
      mechanisms that apply competitive pressure on providers to improve the quality of
      care that they provide and reduce their costs.

PMID- 16284024
TI  - Competition and new technology.
AB  - Most real medical spending growth is accounted for by beneficial but costly new
      technology. This paper argues that a missing dimension of our concepts of
      competition among health plans is a focus on their policy toward new technology.
      In principle, plans could choose to move rapidly or slowly, inclusively or
      selectively, toward adopting new technologies, broadly defined. These policies
      would affect the rates of growth of their premiums, and consumers could choose
      among plans depending on both the technology policy and premium growth. Legal
      impediments, physician resistance, and membership turnover are all possible
      obstacles. Further thought should be given to making technology policy an
      explicit dimension of plan competition.

PMID- 16284025
TI  - Which way for competition? None of the above.
AB  - Despite growing documentation that the conditions needed to support competition
      in health care do not exist, consumer-directed health care has been offered as
      the new market-based solution to cost inflation. Yet typical consumer-based
      insurance products undermine the very logic of expecting consumers to make good
      health care decisions by making preventive services--the category of services
      about which consumers are best able to make informed decisions using their own
      money--exempt from cost sharing. Consumer-directed care threatens important
      societal values--in particular, the goal of establishing relationships between
      patients and clinical professionals based on trust.

PMID- 16284026
TI  - The delivery system matters.
AB  - To meet the quality, affordability, and access challenges of today's health care
      system, the Institute of Medicine's (IOM's) Crossing the Quality Chasm report
      described the critical competencies of a twenty-first-century health care system.
      A growing body of research suggests that the nation's multispecialty group
      practices most nearly meet the delivery system challenges set forth by the IOM. A
      variety of current public and private initiatives and potential policy options
      could act as catalysts for the development and spread of group practice-based,
      accountable delivery systems that are effective and efficient.

PMID- 16284027
TI  - Why employers need to rethink how they buy health care.
AB  - Employers will continue to have a key role in the U.S. health system.
      Unfortunately, their purchasing practices have fallen far short of ideal. Large
      employers can lead the way for smaller companies, but by not routinely using
      competitive bidding or integrating quality into their specifications, they have
      sent mixed messages to both health plans and providers. Employers need to either
      get serious about buying health care as individual companies or explore other
      options. To purchase effectively, both health care expertise and the sustained
      commitment of senior leadership are needed. Whether employers can reverse their
      historical performance and become better purchasers is an open question.

PMID- 16284028
TI  - Consumer-driven health care: just a tweak or a revolution?
AB  - Although some believe that consumer-driven health care amounts to nothing more
      than a tweak to the current system of third-party payment, others see it as a far
      more profound development. They argue that enabling patients to control more of
      their health care dollars will lead to transformation throughout the health care
      system, starting with a demand for information. Once patients control the
      resources and are equipped with information, they will expect health care
      providers to deliver high-quality services at reasonable prices and at the
      convenience of the buyer.

PMID- 16284030
TI  - The 100,000 lives campaign: crystallizing standards of care for hospitals.
AB  - The 100,000 Lives Campaign has the attention of U.S. hospitals, professional
      groups, and the media. Its aim has been endorsed, and its planks are being
      implemented, by more than 2,300 diverse hospitals in every state. We posit that
      the six planks of the campaign have become national standards of care and propose
      four theories of liability for hospitals that ignore the campaign or fail to
      implement its planks. As a result of the campaign, hospitals and their boards now
      face a legal incentive to reduce needless deaths through six specific
      interventions.

PMID- 16284031
TI  - Reporting clinical trial results to inform providers, payers, and consumers.
AB  - Results of randomized clinical trials are the preferred "evidence" for
      establishing the benefits and safety of medical treatments. We present evidence
      suggesting that the conventional approach to reporting clinical trials has
      fundamental flaws that can result in overlooking identifiable subgroups harmed by
      a treatment while underestimating benefits to others. A risk-stratified approach
      can dramatically reduce the chances of such errors. Since professional and
      economic incentives reward advocating treatments for as broad a patient
      population as possible, we suggest that payers and regulatory bodies might need
      to act to motivate prompt, routine adoption of risk-stratified assessments of
      medical treatments' safety and benefits.

PMID- 16284032
TI  - Health savings accounts: early estimates of national take-up.
AB  - The 2003 Medicare Prescription Drug, Improvement, and Modernization Act (MMA)
      approved tax-advantaged health savings accounts (HSAs) for certain high
      deductible health insurance plans. We predict that MMA could lead to
      approximately 3.2 million HSA contracts among Americans ages 19-64 who are not
      students, not enrolled in public health insurance plans, and not eligible for
      group coverage as a dependent. We simulate the effect of several additional tax
      subsidies for HSAs. We predict that the Bush administration's refundable tax
      credit proposal would double HSA take-up and reduce the number of uninsured
      people by 2.9 million, at an annual cost of $8.1 billion.

PMID- 16284033
TI  - A report card on the freshman class of consumer-directed health plans.
AB  - We used a series of case studies of first-generation consumer-directed health
      plans to investigate their early experience and the suitability of their design
      for reducing the growth in health benefit spending and improving the value of
      that spending. We found three fundamental but correctible weaknesses: Most plans
      do not make available comparative measures of quality and longitudinal cost
      efficiency in enough detail to help consumers discern higher-value health care
      options; financial incentives for consumers are weak and insensitive to
      differences in value among the selections that consumers make; and none of the
      plans made cost-sharing adjustments to preserve freedom of choice for low-income
      consumers.

PMID- 16284034
TI  - New cigarette brands with flavors that appeal to youth: tobacco marketing
      strategies.
AB  - Tobacco manufacturers have recently introduced a proliferation of exotic brands
      featuring candylike flavors. We reviewed internal tobacco industry documents and
      patents to assess the role of flavored cigarettes in the targeting of young
      smokers. This research revealed the development of flavor delivery technologies
      hidden from consumers and public health professionals, including the use of a
      plastic pellet placed in the cigarette filter. These findings raise concerns as
      to the potential added health risks associated with using new flavored tobacco
      products, and they underscore the need for effective assessment and monitoring of
      tobacco products.

PMID- 16284035
TI  - The impact of program structure on children's disenrollment from Medicaid and
      SCHIP.
AB  - Program fragmentation might exacerbate disenrollment of children from Medicaid
      and the State Children's Health Insurance Program (SCHIP). Using data from 2001
      2004, I estimated the number of children who switched programs and the number who
      "dropped out" of public insurance--becoming uninsured despite continuing
      eligibility. Roughly two million children a year switched programs; 12.5 percent
      a year dropped out of Medicaid, and 15.6 percent a year dropped out of SCHIP.
      Children in states with separate SCHIP and Medicaid programs were 45 percent more
      likely to drop out. This effect persisted after controlling for demographic and
      policy variables. Administering multiple distinct public insurance programs
      appears to be counterproductive in terms of retention.

PMID- 16284036
TI  - Immigration pediatrics.

PMID- 16284037
TI  - Blind faith and choice.

PMID- 16284038
TI  - The cost of health insurance administration in California: estimates for
      insurers, physicians, and hospitals.
AB  - Administrative costs account for 25 percent of health care spending, but little
      is known about the portion attributable to billing and insurance-related (BIR)
      functions. We estimated BIR for hospital and physician care in California. Data
      for physician practices came from a mail survey and interviews; for hospitals,
      from regulatory reporting; and for private insurers, from a consulting company.
      Private insurers spend 9.9 percent of revenue on administration and 8 percent on
      BIR. Physician offices spend 27 percent and 14 percent, and hospitals, 21 percent
      and 7-11 percent, respectively. Overall, BIR represents 20-22 percent of
      privately insured spending in California acute care settings.

PMID- 16284039
TI  - Legal status and health insurance among immigrants.
AB  - The foreign-born represent a disproportionate share of nonelderly U.S. adults
      without health insurance. Using data from Los Angeles County, we find that most
      of the insurance disparities between the foreign-born and native-born can be
      explained by traditional socioeconomic factors. Undocumented immigrants, however,
      have lower rates of coverage-both private and public-even after a wide array of
      factors are controlled for. Applying Los Angeles County rates to the U.S.
      population implies that undocumented immigrants account for one-third of the
      total increase in the number of uninsured adults in the United States between
      1980 and 2000.

PMID- 16284040
TI  - U.S. adoption of computerized physician order entry systems.
AB  - Computerized physician order entry (CPOE) has been shown to reduce preventable,
      potential adverse events. Despite this evidence, fewer than 5 percent of U.S.
      hospitals have fully implemented these systems. We assess empirically alternative
      reasons for low CPOE implementation using data from various sources. We find that
      CPOE is related to hospital ownership and teaching status; government and
      teaching hospitals are much more likely than other hospital types are to invest
      in CPOE. Hospital profitability is not associated with CPOE investment. Although
      greater diffusion of CPOE is needed, it might have to await continuing publicity
      efforts and substantial reimbursement system changes.

PMID- 16284042
TI  - The impacts of mental health parity and managed care in one large employer group:
      a reexamination.
AB  - Although the impacts of carve-outs to managed behavioral health care
      organizations (MBHOs) and parity mandates on costs are largely settled in the
      literature, their impacts on access are less clear. Here we reexamine a study
      published by Samuel Zuvekas and colleagues in this journal, which found that the
      number of people receiving mental health/substance abuse treatment increased by
      almost 50 percent after the introduction of mental health parity and an MBHO.
      Using multivariate panel data methods, we now suggest that secular trends were
      largely responsible for this increase.

PMID- 16284044
TI  - CDC: HIV prevention efforts.

PMID- 16284045
TI  - Nonprofit drug companies.

PMID- 16284047
TI  - Rural health care.

PMID- 16284048
TI  - What about proxies?

PMID- 16284049
TI  - Misconception about hospice.

PMID- 16284050
TI  - End-of-life care: the authors respond.

PMID- 16284051
TI  - Juries versus judges.

PMID- 16284052
TI  - U.S. and U.K. health spending.

PMID- 16284055
TI  - Drug bills and medicare part D.

PMID- 16284056
TI  - Weekly paclitaxel plus capecitabine in advanced breast cancer patients: dose
      finding trial of GOIRC and GOL.
AB  - BACKGROUND: Paclitaxel and capecitabine have demonstrated a synergic effect and
      significant antitumor activity in patients with advanced breast cancer. A weekly
      schedule of paclitaxel obtained a response rate of 50-68% in advanced breast
      cancer and less serious side-effects. PATIENTS AND METHODS: Thirty-two patients
      with advanced breast cancer pretreated with chemotherapy were enrolled in a dose
      finding trial to determine the maximum tolerated dose (MTD) and the dose-limiting
      toxicity (DLT) of paclitaxel given on days 1, 8 and 15 of each cycle combined
      with capecitabine given twice daily from day 1 through day 14, every 21 days.
      Three patients were recruited at one of six dose levels (paclitaxel 70-100 mg/m2,
      capecitabine 1650-2500 mg/m2). RESULTS: Thirty-two patients were accrued and 31
      were evaluated for toxicity. One DLT has been experienced at level VI as diarrhea
      grade 3. We determined dose level V as the MTD, but we recommend dose level IV
      for phase II studies (capecitabine 1250 mg/m2 orally twice daily plus paclitaxel
      80 mg/m2 intravenously weekly), owing to cumulative toxicity at level V. The
      objective response rate was 43%. CONCLUSIONS: Weekly paclitaxel plus capecitabine
      is a safety and active chemotherapy in previously treated metastatic breast
      cancer.

PMID- 16284057
TI  - Burkitt lymphoma in adults: a prospective study of 72 patients treated with an
      adapted pediatric LMB protocol.
AB  - BACKGROUND: We conducted a phase II study to evaluate in 72 adult patients the
      efficacy of the intensive LMB chemotherapy regimen, previously reported by the
      Societe Francaise d'Oncologie Pediatrique for children with Burkitt lymphoma and
      L3 acute lymphoblastic leukemia. PATIENTS AND METHODS: Treatment began with a
      prephase (low-dose steroids, vincristine and cyclophosphamide), except in
      patients with low tumor burden. Group A (resected stage I and abdominal stage II
      disease) received three courses of vincristine, cyclophosphamide, doxorubicin and
      prednisone. Group B (not eligible for groups A or C) received five courses of
      chemotherapy comprising high-dose methotrexate, infusional cytarabine and
      intrathecal (IT) methotrexate. Group C (patients with central nervous system
      and/or bone marrow involvement with < 30% of blast cells) received eight courses
      containing intensified high-dose methotrexate, high-dose cytarabine, etoposide
      and triple IT injections. RESULTS: The 2 year event-free survival and overall
      survival rates for the 72 patients were 65% and 70%, respectively. Age > or = 33
      years and high lactate dehydrogenase value were associated with a shorter
      survival. No response to COP was also associated with a poor outcome in group B.
      CONCLUSION: Patients with advanced-stage Burkitt lymphoma, including those with
      bone marrow and/or central nervous system involvement, can be cured with a short
      term intensive chemotherapy regime tailored to the tumor burden.

PMID- 16284058
TI  - Phase I trial of UCN-01 in combination with topotecan in patients with advanced
      solid cancers: a Princess Margaret Hospital Phase II Consortium study.
AB  - BACKGROUND: 7-Hydroxystaurosporine (UCN-01) inhibits serine-threonine kinases
      including the Ca2+ and phospholipid-dependent protein kinase C (PKC), CDKs 2, 4,
      6, Chk-1 and PDK1. UCN-01 mediates distinct effects in vitro/in vivo: cell cycle
      arrest in G1, abrogation of G2 arrest by inhibiting chk1, induction of apoptosis
      and potentiation of cytotoxicity of S-phase-active chemotherapeutics including
      the topoisomerase 1 inhibitor topotecan (T). This phase I study was designed to
      determine the maximal tolerated dose (MTD), recommended phase 2 dose (RPTD),
      toxicity profile, pharmacokinetics and antitumor activity of T and UCN-01 in
      patients with refractory solid tumors. DESIGN: Both agents were administered
      every 21 days intravenously through central venous access in escalating doses to
      eligible patients. On day 1, following antiemetic prophylaxis with dexamethasone
      and a serotonin type 3(A) receptor (5HT3) inhibitor, UCN-01 was infused over 3 h,
      followed by T infused over 30 min. On days 2-5, patients received T only. UCN-01
      doses were reduced by 50% in cycles 2 and beyond because of its prolonged half
      life. RESULTS: Thirty-three patients were entered in three cohorts: Dose Level
      (DL) 1 (UCN-01 70 mg/m2, T 0.75 mg/m2), three patients; DL 2 (UCN-01 70 mg/m2, T
      1.0 mg/m2), 24 patients; DL 3 (UCN-01 90 mg/m2, T 1.0 mg/m2), six patients. All
      but three patients were PS 0 or 1, median age was 54 years (range, 29-72), 91%
      were female. Primary tumor types: ovary/peritoneal (23 patients), colon (three
      patients), salivary gland (two patients), others (five patients). All patients
      were eligible for adverse event (AE) analysis and 22 patients were eligible for
      survival and tumor response analysis. Two of six patients had dose limiting
      toxicity (DLT) at DL 3 (grade 3 N/V; grade 4 neutropenia with infection). One DLT
      was seen in one patient at DL 2, consisting of grade 4 leukopenia. This cohort
      was expanded and no further DLTs were observed. Most common drug-related AEs were
      mild (grade 1-2). Non-hematological grade 3-4 AEs consisted of transient
      hyperglycemia (4), infection (3), coagulation, fatigue, hypotension, nausea (2),
      hypomagnesemia, vomiting, headache (1). Hematologic toxicities occurred in 100%
      of patients. Grade 3-4 hematologic abnormalities included neutropenia (16,
      including three with infection), leukopenia (11), lymphopenia (7),
      thrombocytopenia (5). Best response for 22 evaluable patients was PD (8), SD for
      at least six cycles (12), PR (1: carcinoma of ovary, dose level 2) and one not
      assessable. Pharmacokinetic analysis confirmed the prolonged half-life of UCN-01
      of approximately 15 days. CONCLUSIONS: DLT was observed at DL 3 and RPTD was
      determined to be DL 2. To date, this combination has been relatively well
      tolerated with some preliminary evidence of efficacy. A phase II study of this
      combination in patients with ovarian cancer is underway.

PMID- 16284059
TI  - Lymphocyte-rich classical Hodgkin lymphoma (LRCHL): clinico-pathological
      characteristics and outcome of a rare entity.
AB  - BACKGROUND: To investigate the proportion, clinical characteristics and outcome
      of lymphocyte-rich classical Hodgkin lymphoma (LRCHL) in relation to nodular
      lymphocyte predominant HL (NLPHL) and classical HL (cHL). PATIENTS AND METHODS: A
      series of 2743 HL patients of all stages enrolled into three EORTC trials (H7,
      H8, H34) conducted between 1988 and 2000 and forming an unbiased series of HL
      patients was studied. RESULTS: Detailed histological classification after panel
      review was available in 96% of the cases to allow selection of all cases with
      features potentially compatible with the WHO-definition of LRCHL for this study.
      Cases with dominance of lymphocytic infiltrate and relative paucity of
      eosinophils and fibrosis could be selected for re-classification. Twenty-one
      (0.8%) LRCHL cases were identified of which three were originally classified as
      NLPHL, seven as nodular sclerosis HL (NSHL) and 11 as mixed cellularity (MCHL),
      indicating that LRCHL is a rare disease. CONCLUSIONS: Clinical evaluation of the
      unselected series of patients (n = 2743) showed that LRCHL and NLPHL cases more
      often presented with favorable features. Clinical outcome adjusted on ab initio
      patient prognosis did not differ between the three histological entities. These
      results strongly suggest that LRCHL corresponds to an early stage in the spectrum
      of cHL rather than a biologically different disease entity.

PMID- 16284060
TI  - A phase I dose escalation study of continuous oral capecitabine in combination
      with oxaliplatin and pelvic radiation (XELOX-RT) in patients with locally
      advanced rectal cancer.
AB  - PURPOSE: To determine the maximum tolerated dose (MTD) of continuous oral
      capecitabine plus oxaliplatin and pre-operative pelvic radiotherapy (XELOX-RT).
      PATIENTS AND METHODS: Patients with clinically unresectable rectal cancer or for
      whom resection with histologically clear (R0) surgical margins was unlikely
      received continuous capecitabine (500-825 mg/m2 twice daily, 7 days/week),
      oxaliplatin 2-h intravenous infusion (130 mg/m2 days 1 and 29) and pelvic
      radiotherapy (Monday-Friday for 5 weeks, total dose 45 Gy in 25 daily 1.8 Gy
      fractions). The MTD was the capecitabine dose causing dose-limiting toxicities
      (DLTs; treatment-related grade 3/4 toxicities) in one-third or more of patients
      treated per dose level. RESULTS: Eighteen patients received three dose levels.
      The MTD was capecitabine 825 mg/m2 twice daily: DLTs occurred in two of six
      patients (grade 3 diarrhoea, rectal pain with local skin reaction). No DLTs
      occurred in six patients receiving capecitabine 650 mg/m2 twice daily. Grade 3/4
      toxicity was rare, with minimal myelosuppression. Although predominantly a dose
      finding study, XELOX-RT showed promising activity. Fourteen patients had
      histologically confirmed R0 resections and five had a pathological complete
      response. CONCLUSIONS: The recommended dose for further study is capecitabine 650
      mg/m2 twice daily with oxaliplatin and radiotherapy. XELOX-RT showed promising
      antitumour activity. Further evaluation is underway.

PMID- 16284061
TI  - A pilot study to assess the effect of three short-term treatments on frequent
      and/or prolonged bleeding compared to placebo in women using Implanon.
AB  - BACKGROUND: The major side-effect of progestogen-only contraception is disruption
      of menstrual bleeding patterns, which can lead to a high incidence of early
      discontinuation. The aim of this study was to compare three treatments with
      placebo on the duration and recurrence of frequent and/or prolonged bleeding in
      Implanon users. METHOD: Women between the ages of 18 and 45 years, who had used
      Implanon for > or =3 months and were experiencing prolonged or frequent bleeding
      patterns, were recruited at four Australian sites. Subjects were randomized to
      treatment using computer-generated random number table if they met the World
      Health Organization criteria for prolonged and/or frequent bleeding in the
      previous 90 days [Belsey, E.M., Pinol, A.P.Y. and Taskforce on Long-Acting
      Systemic Agents for Fertility Regulation, World Health Organization (1997)
      Contraception 55,57-65]. Treatments were: (1) mifepristone 25 mg given twice on
      day 1 followed by 4 days of twice daily placebo; (2) mifepristone 25 mg given
      twice on day 1 followed by 4 days of ethinyl estradiol (EE) 20 microg in the
      morning and placebo at night; (3) doxycycline 100 mg twice daily for 5 days; and
      (4) placebo twice daily for 5 days. Analysis was by intention to treat. The
      primary endpoint was the number of days of bleeding and spotting immediately
      following initiation of the 5 day course of each active therapy compared with
      placebo. RESULTS: A total of 179 women was assigned to treatment. Both
      mifepristone in combination with EE and doxycycline alone were significantly more
      effective in stopping an episode of bleeding {mean 4. 3 days [confidence interval
      (CI) 3.5-5.2], and 4.8 days (CI 3.9-5.8) respectively} than mifepristone alone or
      placebo [5.9 days (CI 4.8-7.2) and 7.5 days (CI 6.1-9.1) respectively]. No effect
      on subsequent bleeding patterns was observed in any treatment group. CONCLUSION:
      Both mifepristone plus EE and doxycycline alone were significantly more effective
      than placebo in terminating an episode of bleeding in women with prolonged and/or
      frequent bleeding using Implanon. We believe that the observed reduction in the
      number of bleeding days by almost 50% compared to placebo in both the
      mifepristone combination group and the doxycycline group demonstrates a
      clinically significant improvement in bleeding patterns and that further trials
      are needed to compare different combinations of therapy as well as multiple
      dosing regimens in order to establish which is the most effective treatment
      option. The effect of repeat administration or combinations of these preparations
      on long-term bleeding patterns requires further investigation.

PMID- 16284062
TI  - Clinical aspects of Mayer-Rokitansky-Kuester-Hauser syndrome: recommendations for
      clinical diagnosis and staging.
AB  - BACKGROUND: The Mayer-Rokitansky-Kuester-Hauser (MRKH) syndrome is a malformation
      of the female genitals (occurring in one in 4000 female live births) as a result
      of interrupted embryonic development of the Mullerian (paramesonephric) ducts.
      This retrospective study examined the issue of associated malformations,
      subtyping, and the frequency distribution of subtypes in MRKH syndrome. METHODS:
      Fifty-three MRKH patients were investigated using a newly developed standardized
      questionnaire. Together with the results of clinical and diagnostic examinations,
      the patients were classified into the three recognized subtypes [typical,
      atypical and MURCS (Mullerian duct aplasia, renal aplasia, and cervicothoracic
      somite dysplasia)]. RESULTS: The typical form was diagnosed in 25 patients (47%),
      the atypical form in 11 patients (21%), and the most marked form-the MURCS type
      in 17 patients (32%). Associated malformations were notably frequent among the
      patients. Malformations of the renal system were the most frequent type of
      accompanying malformation, with 23 different malformations in 19 patients,
      followed by 18 different skeletal changes in 15 patients. CONCLUSIONS: In
      accordance with the literature, this study shows that associated malformations
      are present in more than a third of cases. Therefore, new basic guidelines for
      standard diagnostic classification involving patients with suspected MRKH are
      presented.

PMID- 16284063
TI  - Preliminary analysis of AZFb region duplication by quantitative real-time PCR.
AB  - BACKGROUND: Deletions of the AZFb region on the long arm of the human Y
      chromosome cause male infertility. However, the reciprocal products of these
      deletion events, AZFb duplications, have not been reported to date. Furthermore,
      it is not known whether potential AZFb duplications represent a risk factor for
      spermatogenic failure. METHODS: A total of 150 patients with male idiopathic
      subfertility (79 non-obstructive azoospermics and 71 oligozoospermics) and 150
      fertile men were analysed for deletion/duplication of the sY125 locus and of the
      JARID1D gene using real-time PCR. RESULTS: Three azoospermic men had deletion of
      the sY125 locus and of the JARID1D gene. No duplication was detected.
      CONCLUSIONS: In our limited sample, AZFb duplications do not appear to be
      associated with male infertility.

PMID- 16284064
TI  - Comparative birth weights of singletons born after assisted reproduction and
      natural conception in previously infertile women.
AB  - BACKGROUND: The possible interference of assisted reproduction techniques (ART)
      with epigenetic reprogramming during early embryo development has recently
      sparked renewed interest about the reported lower birth weight among infants born
      as a consequence of infertility treatments. However, the latter finding so far
      has relied on the comparison of the birth weight of infants conceived with ART to
      general population data. A more appropriate comparison group should involve
      pregnancies in infertile women after natural conception. Therefore, we compared
      neonatal birth weight data of infants born after various ART treatments,
      including intrauterine insemination (IUI), with those of previously infertile
      women achieving pregnancy after sexual intercourse. METHODS: Between August 1996
      and March 2004 the data of all infertile women presenting in the infertility unit
      of the University Women's Hospital of Basel, Switzerland, were collected
      prospectively, adding up to 995 intact pregnancies and deliveries. The birth
      weight of all infants resulting from 741 singleton pregnancies were analysed with
      regard to the patients' characteristics, the occurrence of complications during
      pregnancy and the type of infertility treatment with which the pregnancies were
      achieved. RESULTS: Comparison of duration of pregnancy and birth weight of
      infants born after infertility treatment confirms a shorter pregnancy span and a
      lower mean birth weight in infants born after IVF and ICSI. If women with
      pregnancies after ART deliver before term, neonatal birth weight is significantly
      lower. CONCLUSIONS: There is a specific effect of ART, mainly IVF and ICSI, on
      both shortening the duration of pregnancy and lowering neonatal birth weight.
      Both these parameters seem to be interrelated consequences of some modification
      in the gestational process induced by the infertility treatment. Freezing and
      thawing of oocytes in the pronucleate stage had a lesser impact on pregnancy span
      and on neonatal birth weight.

PMID- 16284065
TI  - Recruitment of sperm donors: the Newcastle-upon-Tyne experience 1994-2003.
AB  - BACKGROUND: The demand for sperm donors has continued despite the introduction of
      ICSI. This study was undertaken in the light of impending changes in donor
      anonymity laws to evaluate the recruitment process of sperm donors. METHODS:
      Retrospective analysis of 1101 potential sperm donors in a tertiary referral
      centre between January 1994 and August 2003. The main outcome measures were to
      determine the demographic details, recruitment rate and reasons for rejection of
      donors. RESULTS: The majority of the applicants were aged <36 years (88.07%),
      students (54.88%), without a partner (53.47%), unmarried (85.38%) and without
      proven fecundity (78.67%). Only 3.63% of the applicants were released as donors,
      30.79% defaulted, whilst 64.48% were rejected. The most common reason for
      rejection was suboptimal semen quality (85.07%). Over the years, the numbers of
      the applicants and released donors have declined significantly. The overall
      clinical pregnancy rate from donor sperm during this period was 23.52%.
      CONCLUSIONS: In this successful anonymous sperm donor programme only a small
      proportion of the applicants are released as donors. The significant decline in
      released sperm donors coupled with the potential effects of loss of donor
      anonymity means that new strategies for sperm donor recruitment are urgently
      required.

PMID- 16284066
TI  - Derivation of human embryonic stem cell lines from embryos obtained after IVF and
      after PGD for monogenic disorders.
AB  - BACKGROUND: Human embryonic stem (hES) cells are pluripotent cells usually
      derived from the inner cell mass (ICM) of blastocysts. Because of their ability
      to differentiate into all three embryonic germ layers, hES cells represent an
      important material for studying developmental biology and cell replacement
      therapy. hES cell lines derived from blastocysts diagnosed as carrying a genetic
      disorder after PGD represent in vitro disease models. METHODS: ICMs isolated by
      immunosurgery from human blastocysts donated for research after IVF cycles and
      after PGD were plated in serum-free medium (except VUB01) on mouse feeder layers.
      RESULTS: Five hES cell lines were isolated, two from IVF embryos and three from
      PGD embryos. All lines behave similarly in culture and present a normal
      karyotype. The lines express all the markers considered characteristic of
      undifferentiated hES cells and were proven to be pluripotent both in vitro and in
      vivo (ongoing for VUB05_HD). CONCLUSIONS: We report here on the derivation of two
      hES cell lines presumed to be genetically normal (VUB01 and VUB02) and three hES
      cell lines carrying mutations for myotonic dystrophy type 1 (VUB03_DM1), cystic
      fibrosis (VUB04_CF) and Huntington disease (VUB05_HD).

PMID- 16284067
TI  - Indomethacin effect on implantation rates in oocyte recipients.
AB  - BACKGROUND: Implantation failure is the main limiting factor for success of IVF.
      Even when transfer techniques are carried out extremely carefully, embryo
      transfer may produce an endometrial and cervical reaction that may result in an
      inflammatory response and impaired implantation. There are no formal
      specifications on the use of indomethacin in reproductive cycles and there are no
      studies published in the scientific literature on its effect on embryo
      implantation. Oocyte donation is the best model to evaluate the determinants of
      implantation. The aim of this study is to evaluate the potential benefit of
      indomethacin administered at embryo transfer. METHODS: A randomized pilot trial
      of 136 oocyte recipients was carried out. Seventy-two women received standard
      specifications plus 100 mg of indomethacin rectally given as three doses every 12
      h starting on the night prior to transfer. RESULTS: Positive HCG (>= 6 mUI/ml)
      occurred in 59.7% of treated women and in 59.4% of women in the control group.
      Implantation rates were 27.8% in the indomethacin group and 26.4% in the
      controls. CONCLUSIONS: The indomenthacin group did not show significantly higher
      implantation rates. A larger study exploring alternative treatment protocols
      might be appropriate.

PMID- 16284068
TI  - Patient perspectives on multiple medications versus combined pills: a qualitative
      study.
AB  - BACKGROUND: A growing number of patients are taking multiple medications.
      Unfortunately, adherence may fall as drug numbers and procedural complexity
      increase. While there are plausible theoretical reasons why combining pills might
      improve non-adherence, patients' attitudes are unknown. AIM: To explore attitudes
      and practices to medication regimens among patients already in receipt of
      multiple medications, and to assess whether a combined tablet would be perceived
      as advantageous. DESIGN: Qualitative study. METHODS: Ninety-two men and women
      aged >40 years currently receiving both antihypertensive and cholesterol-lowering
      medications took part in 14 focus groups. RESULTS: Drugs were seen as unwelcome
      but necessary. Some took drugs flexibly by changing dose timing, thereby
      increasing the complexity of their regimen. A routine was seen as the key to
      coping with multiple medications, although it was sometimes threatened by changes
      in prescriptions and life circumstances. While some participants welcomed a
      combined pill, there was uncertainty about whether a combination that mirrored
      their current doses would be available. There were also concerns about tablet
      size, allergies, the attribution of side-effects, timing of tablets throughout
      the day, and the ability to alter dose levels. CONCLUSION: While some patients
      would be willing to try a combined pill and would appreciate the associated
      convenience, they are likely to have a number of concerns that prescribers should
      address. Willingness to move to combined therapy may be hindered if drug
      combinations that mirror personalized and trusted regimens are not available.

PMID- 16284069
TI  - Ions in smooth muscle, now and then.

PMID- 16284070
TI  - Adenylate cyclase 5 and KCa1.1 channel are required for EGFR up-regulation of
      PCNA in native contractile rat basilar artery smooth muscle.
AB  - In synthetic phenotype vascular smooth muscle cells (VSMC), activation of
      epidermal growth factor (EGF) receptor (EGFR) induces a sustained increase in
      intermediate conductance K(Ca) (int-K(Ca); K(Ca)3.1) channels that is essential
      for proliferation. However, a comparable mechanism has not been identified in
      native contractile phenotype VSMC, which express large conductance K(Ca) (maxi
      K(Ca); K(Ca)1.1) channels, not int-K(Ca) channels. Using patch clamp of freshly
      isolated contractile VSMC from rat basilar artery, we found that EGF (100 ng ml(
      1)) caused hyperpolarization (7.9 +/- 3.9 mV) due to activation of iberiotoxin
      sensitive, maxi-K(Ca) channels. The EGFR ligands EGF (100 ng ml(-1)),
      transforming growth factor alpha (0.4 ng ml(-1)) and heparin-binding EGF (100 ng
      ml(-1)) all caused a 20% increase in maxi-K(Ca) channel current that was blocked
      by AG-1478 or by knock-down of EGFR expression using cisterna magna infusion of
      antisense oligodeoxynucleotide (AS-ODN). In controls, EGFR knock-down, and EGFR
      gain-of-expression (angiotensin II hypertension), the increase in maxi-K(Ca)
      current correlated with the abundance of EGFR protein expressed. The EGFR
      mediated increase in maxi-K(Ca) channel activity was blocked by inhibiting cAMP
      dependent protein kinase (cAK) using KT-5720 or Rp-cAMP, or by inhibiting
      adenylate cyclase type 5 (AC-5) using 2',5'-dideoxyadenosine or knock-down of AC
      5 expression by intracisternal AS-ODN. Direct infusion of EGF into cisterna magna
      caused up-regulation of proliferating cell nuclear antigen (PCNA) in VSMC that
      was prevented by coinfusion of iberiotoxin or of AG-1478. Our data, which are
      consistent with the hypothesis that hyperpolarization is critical for a
      proliferative response, are the first to implicate AC-5 and maxi-K(Ca) channels
      in gene activation related to EGFR signalling in native contractile VSMC.

PMID- 16284071
TI  - Adenosine concentration in the porcine coronary artery wall and A2A receptor
      involvement in hypoxia-induced vasodilatation.
AB  - We tested whether hypoxia-induced coronary artery dilatation could be mediated by
      an increase in adenosine concentration within the coronary artery wall or by an
      increase in adenosine sensitivity. Porcine left anterior descendent coronary
      arteries, precontracted with prostaglandin F(2alpha) (10(-5) M), were mounted in
      a pressure myograph and microdialysis catheters were inserted into the tunica
      media. Dialysate adenosine concentrations were analysed by HPLC. Glucose, lactate
      and pyruvate were measured by an automated spectrophotometric kinetic enzymatic
      analyser. The exchange fraction of [(14)C]adenosine over the microdialysis
      membrane increased from 0.32 +/- 0.02 to 0.46 +/- 0.02 (n = 4, P < 0.01) during
      the study period. At baseline, interstitial adenosine was in the region of 10 nM
      which is significantly less than previously found myocardial concentrations.
      Hypoxia (P(O(2)) 30 mmHg for 60 min, n = 5) increased coronary diameters by 20.0
      +/- 2.6% (versus continuous oxygenation -3.1 +/- 2.4%, n = 6, P < 0.001) but
      interstitial adenosine concentration fell. Blockade of adenosine deaminase (with
      erythro-9-(2-hydroxy-3-nonyl-)-adenine, 5 microM), adenosine kinase (with
      iodotubericidine, 10 microM) and adenosine transport (with n
      nitrobenzylthioinosine, 1 microM) increased interstitial adenosine but the
      increase was unrelated to hypoxia or diameter. A coronary dilatation similar to
      that during hypoxia could be obtained with 30 microM of adenosine in the organ
      bath and the resulting interstitial adenosine concentrations (n = 5) were 20
      times higher than the adenosine concentration measured during hypoxia. Adenosine
      concentration-response experiments showed vasodilatation to be more pronounced
      during hypoxia (n = 9) than during normoxia (n = 9, P < 0.001) and the A(2A)
      receptor antagonist ZM241385 (20 nM, n = 5), attenuated hypoxia-induced
      vasodilatation while the selective A(2B) receptor antagonist MRS1754 (20 nM, n =
      4), had no effect. The lactate/pyruvate ratio was significantly increased in
      hypoxic arteries but did not correlate with adenosine concentration. We conclude
      that hypoxia-induced coronary artery dilatation is not mediated by increased
      adenosine produced within the artery wall but might be facilitated by increased
      adenosine sensitivity at the A(2A) receptor level.

PMID- 16284072
TI  - Spatial segregation of neuronal calcium signals encodes different forms of LTP in
      rat hippocampus.
AB  - Calcium regulates numerous processes in the brain. How one signal can coordinate
      so many diverse actions, even within the same neurone, is the subject of intense
      investigation. Here we have used two-photon calcium imaging to determine the
      mechanism that enables calcium to selectively and appropriately induce different
      forms of long-term potentiation (LTP) in rat hippocampus. Short-lasting LTP (LTP
      1) required activation of ryanodine receptors (RyRs), which selectively increased
      calcium in synaptic spines. LTP of intermediate duration (LTP 2) was dependent on
      activation of inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) and subsequent
      calcium release specifically in dendrites. Long-lasting LTP (LTP 3) was
      selectively dependent on L-type voltage-dependent calcium channels (L-VDCCs),
      which generated somatic calcium influx. Activation of NMDA receptors was
      necessary, but not sufficient, for the generation of appropriate calcium signals
      in spines and dendrites, and the induction of LTP 1 and LTP 2. These results
      suggest that the selective induction of different forms of LTP is achieved via
      spatial segregation of functionally distinct calcium signals.

PMID- 16284073
TI  - Neuronal responses to transient hypoglycaemia in the dorsal vagal complex of the
      rat brainstem.
AB  - Several regions of the mammalian brain contain glucosensing neurones. In vivo
      studies have suggested that those located in the hypothalamus and lower brainstem
      are involved in glucoprivic feeding and homeostatic control of blood glucose. We
      have identified and characterized hypoglycaemia-sensitive neurones in the dorsal
      vagal complex of the brainstem using in situ hybridization, single-cell RT-PCR
      and whole-cell patch-clamp recordings from rat brainstem slices. Approximately
      80% of neurones did not respond to hypoglycaemia (changing artificial
      cerebrospinal fluid (ACSF) glucose from 10 mM to 0 mM) within 5 min (non
      responsive: NR). Another 10% depolarized within 155+/-31 s (mean+/-s.e.m.) of
      glucose removal (glucose-inhibited: GI), and the remaining neurones
      hyperpolarized within 53+/-7 s (glucose-excited: GE). The hyperpolarization was
      reversed by the KATP channel blocker tolbutamide. Single-cell RT-PCR revealed
      that GI and GE, but not NR, cells expressed glucokinase (GLK). In contrast, SUR1,
      a KATP channel subunit, was expressed in GE and some NR cells. In situ
      hybridization with biotin-labelled riboprobes in the dorsal vagal complex
      revealed ubiquitous expression of SUR1, and widespread, but sparse, expression of
      GLK. Identification of astrocytes using a GFAP (glial fibrillary acidic protein)
      antibody showed that GLK and GFAP were not colocalized. In summary, we have
      demonstrated that GI and GE neurones exist in the brainstem and that GLK is
      essential for their function. It seems likely that GE neurones work in a way
      analogous to pancreatic beta-cells in that they require both GLK and KATP
      channels.

PMID- 16284074
TI  - Retinal ganglion cell activity from the multifocal electroretinogram in pig:
      optic nerve section, anaesthesia and intravitreal tetrodotoxin.
AB  - Non-invasive recordings of the retinal activity have an important role to play in
      the diagnosis of retinal pathologies. The detection of diseases that involve
      retinal ganglion cells (RGCs), such as optic atrophy and glaucoma, may be
      improved by isolating the RGC contribution from the multifocal electroretinogram
      (mfERG). In this study, mfERGs were performed on 20 pigs, 1-6 weeks following
      unilateral retrobulbar optic nerve section (ONS). The stimuli were 103 non-scaled
      high-contrast hexagons from which summed and individual mfERG responses were
      obtained in experimental and control fellow eyes under conditions of ketamine (n
      = 11) or isoflurane anaesthesia (n = 9). The effect of intravitreal injection of
      tetrodotoxin (TTX; n = 6) was also investigated. The summed mfERG responses
      showed a first positive peak (P1) with a short latency (21 ms) followed by two
      smaller peaks (P2 and P3) of longer latency (46 and 65 ms, respectively). While
      P2 and P3 amplitude were highly correlated with the time post-optic nerve section
      (ONS) (P2: r(2) = 0.669; P = 0.007; P3: r(2) = 0.651; P = 0.005), P1 was not
      (r(2) = 0.193; P = 0.38). P1 and P2 showed no implicit time variation as a
      function of retinal location, while P3 implicit time varied along the axis of the
      visual streak, generating a naso-temporal asymmetry. However, the P3 implicit
      time did not vary consistently with distance away from the optic nerve head.
      Intravitreal injections of TTX reduced P2 and P3 in the control eyes, consistent
      with the effect of ONS, and also induced a series of regular oscillations lasting
      up to 200 ms post stimulus. Under isoflurane anaesthesia, all components of the
      mfERG ifn experimental and control eyes were, at all time points post-ONS, of
      similar amplitude and without naso-temporal asymmetry, suggesting a reduced
      participation of RGCs under these anaesthesic conditions. These data clearly
      demonstrate that it is possible to isolate the RGC contribution from non-invasive
      multifocal electroretinography.

PMID- 16284075
TI  - Ca2+-calmodulin-dependent myosin light chain kinase is essential for activation
      of TRPC5 channels expressed in HEK293 cells.
AB  - Mammalian homologues of Drosophila transient receptor potential (TRP) proteins
      are responsible for receptor-activated Ca(2+) influx in vertebrate cells. We
      previously reported the involvement of intracellular Ca(2+) in the receptor
      mediated activation of mammalian canonical transient receptor potential 5 (TRPC5)
      channels. Here we investigated the role of calmodulin, an important sensor of
      changes in intracellular Ca(2+), and its downstream cascades in the activation of
      recombinant TRPC5 channels in human embryonic kidney (HEK) 293 cells. Ca(2+)
      entry through TRPC5 channels, induced upon stimulation of the G-protein-coupled
      ATP receptor, was abolished by treatment with W-13, an inhibitor of calmodulin.
      ML-9 and wortmannin, inhibitors of Ca(2+)-calmodulin-dependent myosin light chain
      kinase (MLCK), and the expression of a dominant-negative mutant of MLCK inhibited
      the TRPC5 channel activity, revealing an essential role of MLCK in maintaining
      TRPC5 channel activity. It is important to note that ML-9 impaired the plasma
      membrane localization of TRPC5 channels. Furthermore, TRPC5 channel activity
      measured using the whole-cell patch-clamp technique was inhibited by ML-9,
      whereas TRPC5 channel activity observed in the cell-excised, inside-out patch was
      unaffected by ML-9. An antibody that recognizes phosphorylated myosin light chain
      (MLC) revealed that the basal level of phosphorylated MLC under unstimulated
      conditions was reduced by ML-9 in HEK293 cells. These findings strongly suggest
      that intracellular Ca(2+)-calmodulin constitutively activates MLCK, thereby
      maintaining TRPC5 channel activity through the promotion of plasma membrane TRPC5
      channel distribution under the control of phosphorylation/dephosphorylation
      equilibrium of MLC.

PMID- 16284076
TI  - Cardiac memory ... new insights into molecular mechanisms.
AB  - 'Cardiac memory' describes an electrocardiographic T wave vector change, recorded
      during normal sinus rhythm that reflects the QRS complex vector during prior
      periods of ventricular pacing or arrhythmia. In this brief review we consider the
      mechanisms responsible for cardiac memory, which offer a unique window for
      relating molecular determinants of repolarization to their expression in the
      function of ion channels and in the electrophysiology of the heart. Understanding
      the steps that translate the molecular mechanisms for memory into clinical
      expression in this relatively straightforward model facilitates our comprehension
      of the complex pathways that order normal cardiac repolarization and
      repolarization changes.

PMID- 16284077
TI  - Preparing for the first breath: prenatal maturation of respiratory neural
      control.
AB  - By birth, the regulatory neural network responsible for respiratory control is
      capable of generating robust rhythm-driving ventilation that can adjust to
      homeostatic needs. The advent of in vitro models isolated from prenatal rodents
      has significantly advanced our understanding of these processes. In this topical
      review, we examine the development of medullary respiratory rhythm-generating
      centres and phrenic motoneurone-diaphragm properties during the prenatal period.

PMID- 16284078
TI  - An amino-terminal lysine residue of rat connexin40 that is required for spermine
      block.
AB  - Spermine blocks connexin40 (Cx40) gap junctions, and two cytoplasmic amino
      terminal domain glutamate residues are essential for this inhibitory activity. To
      further examine the molecular basis for block, we mutated a portion of a basic
      amino acid (HKH) motif on the Cx40 amino-terminal domain. Replacement of the Cx40
      H15 + K16 residues with the Q15 + A16 sequence native to spermine-insensitive
      connexin43 (Cx43) gap junctions increased the equilibrium dissociation constant
      (K(d)) and reduced the maximum inhibition by spermine. The corresponding
      electrical distance (delta) approximation was decreased by about 50%. The
      transjunctional voltage (V(j))-dependent gating of homotypic Cx40 H15Q + K16A
      mutant gap junctions was also significantly reduced. The minimum normalized
      steady-state junctional conductance (G(min)) increased from 0.17 to 0.72, with an
      increase in the half-inactivation voltage from 48 to 60 mV. However, the unitary
      junctional conductance (gamma(j); 160 pS) was only slightly altered, and the
      relative cation/anion conductance and permeability ratios were unchanged from
      wild-type Cx40 gap junction channels. The relative K(+)/Cl(-) permeability
      (P(K)/P(Cl)) ratio increased from six to ten when [KCl] was reduced to 25% of
      normal. These data suggest that the HKH motif at positions 15-17 is important to
      the conformational structure of the putative voltage sensor and spermine receptor
      of Cx40, without causing significant alteration of the electrostatic surface
      charge potentials that contribute to the ion selectivity of this gap junction
      channel.

PMID- 16284079
TI  - Rapid glucose sensing by protein kinase A for insulin exocytosis in mouse
      pancreatic islets.
AB  - The role of protein kinase A (PKA) in insulin exocytosis was investigated with
      the use of two-photon excitation imaging of mouse islets of Langerhans.
      Inhibitors of PKA selectively reduced the number of exocytic events during the
      initial period (< 250 s) of the first phase of glucose-induced exocytosis (GIE),
      without affecting the second phase, in intact islets or small clusters of islet
      cells. The PKA inhibitors did not reduce the extent of the glucose-induced
      increase in [Ca(2+)](i). The actions of glucose and PKA in Ca(2+)-induced insulin
      exocytosis (CIE) triggered by photolysis of a caged-Ca(2+) compound, which
      resulted in large increases in [Ca(2+)](i) and thereby bypassed the ATP-sensitive
      K(+) channel-dependent mechanism of glucose sensing, were therefore studied. A
      high concentration (20 mM) of glucose potentiated CIE within 1 min, and this
      effect was blocked by inhibitors of PKA. This PKA-dependent action of glucose
      required glucose metabolism, given that increasing the intracellular
      concentration of cAMP by treatment with forskolin potentiated CIE only at the
      high glucose concentration. Finally, PKA appeared to reduce the frequency of
      'kiss-and-run' exocytic events and to promote full-fusion events during GIE.
      These data indicate that a PKA-dependent mechanism of glucose sensing, which is
      operative even at the basal level of PKA activity, plays an important role
      specifically in the first phase of GIE, and they suggest that the action of PKA
      is mediated at the level of the fusion reaction.

PMID- 16284080
TI  - The receptor site of the spider toxin PcTx1 on the proton-gated cation channel
      ASIC1a.
AB  - Acid-sensing ion channels (ASICs) are excitatory neuronal cation channels,
      involved in physiopathological processes related to extracellular pH fluctuation
      such as nociception, ischaemia, perception of sour taste and synaptic
      transmission. The spider peptide toxin psalmotoxin 1 (PcTx1) has previously been
      shown to inhibit specifically the proton-gated cation channel ASIC1a. To identify
      the binding site of PcTx1, we produced an iodinated form of the toxin ((125)I
      PcTx1Y(N)) and developed a set of binding and electrophysiological experiments on
      several chimeras of ASIC1a and the PcTx1-insensitive channels ASIC1b and ASIC2a.
      We show that (125)I-PcTx1Y(N) binds specifically to ASIC1a at a single site, with
      an IC(50) of 128 pM, distinct from the amiloride blocking site. Results obtained
      from chimeras indicate that PcTx1 does not bind to ASIC1a transmembrane domains
      (M1 and M2), involved in formation of the ion pore, but binds principally on both
      cysteine-rich domains I and II (CRDI and CRDII) of the extracellular loop. The
      post-M1 and pre-M2 regions, although not involved in the binding site, are
      crucial for the ability of PcTx1 to inhibit ASIC1a current. The linker domain
      between CRDI and CRDII is important for their correct spatial positioning to form
      the PcTx1 binding site. These results will be useful for the future
      identification or design of new molecules acting on ASICs.

PMID- 16284081
TI  - Gastric electrical stimulation inhibits postprandial antral tone partially via
      nitrergic pathway in conscious dogs.
AB  - Gastric electrical stimulation (GES) has recently been explored as a therapeutic
      option for gastrointestinal motility disorders or obesity. The mechanism behind
      it is not fully elucidated. The aims of this study were to assess the effects of
      GES with different parameters on antral tone and to explore the involvement of
      the nitrergic pathway. Eight dogs equipped with a gastric cannula and one pair of
      serosal electrodes in the greater curvature 4 cm above the pylorus were studied
      on separate days. The study was composed of seven randomized sessions in the fed
      state [control, GES with different parameters, and GES plus neuronal nitric oxide
      synthase (nNOS) inhibitor]. Each session included three consecutive 30-min
      periods (baseline, GES, and recovery). GES was performed with long pulses or
      pulse trains. The antral volume was measured using an intragastric balloon
      connected with a barostat device. Behaviors of the dogs during each stimulation
      period were also noted. We found that 1) postprandial antral tone was reduced
      with GES with all tested parameter settings, reflected as a significant and
      substantial increase in antral volume ranging from 179 to 309%; 2) the inhibitory
      effect of GES on antral tone was partially blocked (decreased by 39.5%) with an
      nNOS inhibitor; and 3) mild symptoms were induced with GES and found to be
      correlated with the GES-induced increase in antral volume. We conclude that
      retrograde GES with long pulses or pulse trains inhibits antral tone, and this
      inhibitory effect is partially mediated via the nitrergic pathway. These results
      suggest that retrograde GES may have a therapeutic potential for obesity.

PMID- 16284082
TI  - Peripherally administered CRF stimulates colonic motility via central CRF
      receptors and vagal pathways in conscious rats.
AB  - Corticotropin releasing factor (CRF) is one of the most important factors in the
      mechanism of stress-induced stimulation of colonic motility. However, it is
      controversial whether stress-induced stimulation of colonic motility is mediated
      via central or peripheral CRF receptors. We investigated the hypothesis that
      peripherally injected CRF accelerates colonic motility through the central CRF
      receptor, but not the peripheral CRF receptor. A strain gauge transducer was
      sutured on the serosal surface of the proximal colon. Colonic motility was
      monitored before and after the peripheral injection of CRF. An in vitro muscle
      strip study was also performed to investigate the peripheral effects of CRF.
      Subcutaneous injection of CRF (30-100 microg/kg) stimulated colonic motility in a
      dose-dependent manner. The stimulatory effect of peripherally administered CRF on
      colonic motility was abolished by truncal vagotomy, hexamethonium, atropine, and
      intracisternal injection of astressin (a CRF receptor antagonist). No responses
      to CRF (10(-9) -10(-7) M) of the muscle strips of the proximal colon were
      observed. These results suggest that the stimulatory effect of colonic motility
      in response to peripheral administration of CRF is mediated by the vagus nerve,
      nicotinic receptors, muscarinic receptors, and CRF receptors of the brain stem.
      It is concluded that peripherally administered CRF reaches the area postrema and
      activates the dorsal nucleus of vagi via central CRF receptors, resulting in
      stimulation of the vagal efferent and cholinergic transmission of the proximal
      colon.

PMID- 16284083
TI  - No effect of short-term 17beta-estradiol supplementation in healthy men on
      systemic inflammatory responses to exercise.
AB  - Sex-based differences in inflammatory responses to exercise may be mediated by
      estrogen through increased muscle membrane stability and/or inhibited cytokine
      production. In this study, in vivo effects of estrogen on systemic inflammation
      related responses to exercise were assessed in healthy men. In a double-blind,
      placebo-controlled, crossover design, 11 men cycled for 90 min at 65% Vo2 max
      after 8 days of 17beta-estradiol supplementation (ES; 2 mg/day) or placebo (PL;
      glucose polymer). After a 2-wk washout, exercise was repeated after 8 days on the
      alternate treatment. Blood was collected pre- and postexercise to determine IL-6,
      soluble intercellular adhesion molecule-1 (sICAM-1), neutrophil counts, and
      cortisol. Preexercise serum was assayed for sex hormones. ES increased estradiol
      (133+/-71 to 840+/-633 pmol/l, P=0.005) and reduced testosterone (19.9+/-3.7 to
      16.1+/-3.9 nmol/l, P=0.007). Exercise increased cortisol (P=0.02), IL-6 (P<0.001)
      and neutrophil counts (P<0.001) with no influence on sICAM-1 (P=0.34) and no
      effect of ES on these changes. Postexercise IL-6 and neutrophil counts were
      correlated (r=0.58, P=0.005); postexercise IL-6 and cortisol (r=0.18, P=0.43) and
      postexercise cortisol and neutrophil counts (r=0.06, P=0.78) were not.
      Postexercise sICAM-1 was not correlated with the above variables (P>or=0.79). In
      conclusion, 8 days of ES in healthy men did not influence systemic inflammation
      related responses to acute exercise. Future studies should investigate 17beta
      estradiol effects on IL-6 production and neutrophil infiltration within skeletal
      muscle during and after exercise.

PMID- 16284084
TI  - Differential regulation of suppressor of cytokine signaling-3 in the liver and
      adipose tissue of the sheep fetus in late gestation.
AB  - It is unknown whether the JAK/STAT/suppressor of cytokine signaling-3 (SOCS-3)
      intracellular signaling pathway plays a role in tissue growth and metabolism
      during fetal life. We investigated whether there is a differential profile of
      SOCS-3 expression in the liver and perirenal adipose tissue during the period of
      increased fetal growth in late gestation and the impact of fetal growth
      restriction on SOCS-3 expression in the fetal liver. We also determined whether
      basal SOCS-3 expression in the fetal liver and perirenal adipose tissue is
      regulated by endogenous fetal prolactin (PRL). SOCS-3 mRNA abundance was higher
      in the liver than in the pancreas, spleen, and kidney of the sheep fetus during
      late gestation. In the liver, SOCS-3 mRNA expression was increased (P < 0.05)
      between 125 (n = 4) and 145 days (n = 7) gestation and lower (P < 0.05) in growth
      restricted compared with normally grown fetal sheep in late gestation. The
      relative expression of SOCS-3 mRNA in the fetal liver was directly related to the
      mean plasma PRL concentrations during a 48-h infusion of either a dopaminergic
      agonist, bromocriptine (n = 7), or saline (n = 5), such that SOCS-3 mRNA
      expression was lower when plasma PRL concentrations decreased below approximately
      20 ng/ml [y = 0.99 - (2.47/x) + (4.96/x(2)); r(2) = 0.91, P < 0.0001, n = 12]. No
      relationship was shown between the abundance of phospho-STAT5 in the fetal liver
      and circulating PRL. SOCS-3 expression in perirenal adipose tissue decreased (P <
      0001) between 90-91 (n = 6) and 140-145 days (n = 9) gestation and was not
      related to endogenous PRL concentrations. Thus SOCS-3 is differentially expressed
      and regulated in key fetal tissues and may play an important and tissue-specific
      role in the regulation of cellular proliferation and differentiation before
      birth.

PMID- 16284085
TI  - Modulation of the baroreceptor reflex by the dorsomedial hypothalamic nucleus and
      perifornical area.
AB  - Neurons within the dorsomedial hypothalamic nucleus (DMH) and perifornical area
      (PeF), which lie within the classic hypothalamic defense area, subserve the
      cardiovascular response to psychological stress. Previous studies have shown that
      electrical stimulation of the hypothalamic defense area causes inhibition of the
      cardiac and (in some cases) sympathetic components of the baroreceptor reflex. In
      contrast, naturally evoked psychological stress does not appear to be associated
      with such inhibition. In this study, we tested the effect of specific activation
      of neurons within the DMH and PeF on the baroreflex control of renal sympathetic
      nerve activity and heart rate in urethane-anesthetized rats. Microinjection of
      bicuculline (a GABA(A) receptor antagonist) into the DMH caused dose-dependent
      increases in heart rate and renal sympathetic activity, shifted the baroreflex
      control of both variables to higher levels (i.e., increased the upper and lower
      plateaus of the baroreflex function curves, and increased the threshold,
      midpoint, and saturation levels of mean arterial pressure). The maximum gain of
      the sympathetic component of the baroreflex was also increased, while that of the
      cardiac component was not significantly changed. Increases in the midpoint were
      very similar in magnitude to the evoked increases in baseline mean arterial
      pressure. Microinjection of bicuculline into the PeF evoked very similar effects.
      The results indicate that disinhibition of neurons in the DMH/PeF region not only
      increases sympathetic vasomotor activity and heart rate but also resets the
      baroreceptor reflex such that it remains effective, without any decrease in
      sensitivity, over a higher operating range of arterial pressure.

PMID- 16284086
TI  - Opiate slowing of feline respiratory rhythm and effects on putative medullary
      phase-regulating neurons.
AB  - Opiates have effects on respiratory neurons that depress tidal volume and air
      exchange, reduce chest wall compliance, and slow rhythm. The most dose-sensitive
      opioid effect is slowing of the respiratory rhythm through mechanisms that have
      not been thoroughly investigated. An in vivo dose-response analysis was performed
      on medullary respiratory neurons of adult cats to investigate two untested
      hypotheses related to mechanisms of opioid-mediated rhythm slowing: 1) Opiates
      suppress intrinsic conductances that limit discharge duration in medullary
      inspiratory and expiratory neurons, and 2) opiates delay the onset and lengthen
      the duration of discharges postsynaptically in phase-regulating postinspiratory
      and late-inspiratory neurons. In anesthetized and unanesthetized decerebrate
      cats, a threshold dose (3 microg/kg) of the mu-opioid receptor agonist fentanyl
      slowed respiratory rhythm by prolonging discharges of inspiratory and expiratory
      bulbospinal neurons. Additional doses (2-4 microg/kg) of fentanyl also lengthened
      the interburst silent periods in each type of neuron and delayed the rate of
      membrane depolarization to firing threshold without altering synaptic drive
      potential amplitude, input resistance, peak action potential frequency, action
      potential shape, or afterhyperpolarization. Fentanyl also prolonged discharges of
      postinspiratory and late-inspiratory neurons in doses that slowed the rhythm of
      inspiratory and expiratory neurons without altering peak membrane depolarization
      and hyperpolarization, input resistance, or action potential properties. The
      temporal changes evoked in the tested neurons can explain the slowing of network
      respiratory rhythm, but the lack of significant, direct opioid-mediated membrane
      effects suggests that actions emanating from other types of upstream bulbar
      respiratory neurons account for rhythm slowing.

PMID- 16284087
TI  - Acute inhibition of the endogenous xanthine oxidase improves renal hemodynamics
      in hypercholesterolemic pigs.
AB  - Hypercholesterolemia (HC), a major risk factor for onset and progression of renal
      disease, is associated with increased oxidative stress, potentially causing
      endothelial dysfunction. One of the sources of superoxide anion is xanthine
      oxidase (XO), but its contribution to renal endothelial function in HC remains
      unclear. We tested the hypothesis that XO modulates renal hemodynamics and
      endothelial function in HC pigs. Four groups (n = 23) of female domestic pigs
      were studied 12 wk after either normal (n = 11) or HC diet (n = 12). Oxidative
      stress was assessed by plasma isoprostanes and oxidized LDL, and the XO system by
      plasma uric acid, urinary xanthine, and renal XO expression (by immunoblotting
      and immunohistochemistry). Renal hemodynamics and function were studied with
      electron beam-computed tomography before and after endothelium-dependent (ACh)
      and -independent (sodium nitroprusside) challenge, during a concurrent intrarenal
      infusion of either oxypurinol or saline (n = 5-6 in each group). HC showed
      elevated oxidative stress, higher plasma uric acid (23.8 +/- 3.8 vs. 6.2 +/- 0.8
      microM/mM creatinine, P = 0.001), lower urinary xanthine, and greater renal XO
      expression compared with normal. Inhibition of XO in HC significantly improved
      the blunted responses to ACh of cortical perfusion (13.5 +/- 12.1 and 37.2 +/-
      10.6%, P = 0.01 and P = not significant vs. baseline, respectively), renal blood
      flow, and glomerular filtration rate; restored medullary perfusion; and improved
      the blunted cortical perfusion response to sodium nitroprusside. This study
      demonstrates that the endogenous XO system is activated in swine HC. Furthermore,
      it suggests an important role for XO in regulation of renal hemodynamics,
      function, and endothelial function in experimental HC.

PMID- 16284088
TI  - Ischemic acute renal failure induces the expression of a wide range of
      nephrogenic proteins.
AB  - Ischemia-induced acute renal failure (ARF) is a disorder with high morbidity and
      mortality. ARF is characterized by a regeneration phase, yet its molecular basis
      is still under study. Changes in gene expression have been reported in ARF, and
      some of these genes are specific for nephrogenic processes. We tested the
      hypothesis that the regeneration process developed after ischemia-induced ARF can
      be characterized by the reexpression of important regulatory proteins of kidney
      development. The distribution pattern and levels of nephrogenic proteins in rat
      kidneys after ischemia were studied by immunohistochemistry and immunoblot
      analysis. Ischemic damage was assessed by conventional morphology, serum
      creatinine, and the apoptotic markers terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling (TUNEL) and caspase 3. The hypoxia levels induced
      by ischemia were assessed by specific markers: hypoxia induced factor (HIF)
      1alpha and 2-pimonidazole. In kidneys with ARF, an important initial damage was
      observed through periodic acid Schiff staining, by the induction of damage
      markers alpha-smooth muscle actin (alpha-SMA) and macrophages (ED-1) and by
      apoptosis induction. In agreement with diminishing renal damage at the initial
      reparation phase, the expression of the mesenchymal proteins vimentin, neural
      cell adhesion molecules (Ncam), and the epithelial markers, Pax-2, Noggin, and
      basic fibroblast growth factor was observed; after, in a second phase, the
      tubular markers bone morphogen protein 7, Engrailed, and Lim-1, as well as the
      transcription factors Smad and p-Smad, were observed. Additionally, the
      endothelial markers VEGF and Tie-2 were induced at the initial and middle stages
      of regeneration phase, respectively. The expression of these proteins was
      restricted in time and space, as well as spatially and temporally. Because all of
      these proteins are important in maintaining a functional kidney, these results
      suggest that during the regeneration process after induced hypoxia, these
      nephrogenic proteins can be reexpressed in a similar fashion to that observed
      during development, thus restoring mature kidney function.

PMID- 16284089
TI  - Blunted hypertensive effect of combined fructose and high-salt diet in gene
      targeted mice lacking functional serum- and glucocorticoid-inducible kinase SGK1.
AB  - Serum- and glucocorticoid-inducible kinase (SGK1) is transcriptionally
      upregulated by mineralocorticoids and activated by insulin. The kinase stimulates
      the renal epithelial Na(+) channel and may thus participate in blood pressure
      regulation. Hyperinsulinemia is triggered by dietary fructose, which sensitizes
      blood pressure for salt intake. The role of SGK1 in hypertensive effects of
      combined fructose and high-salt intake was thus explored in SGK1 knockout mice
      (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Renal SGK1 transcript
      levels of sgk1(+/+) mice were significantly elevated after fructose diet. Under
      control diet, fluid intake, urinary flow rate, urinary Na(+), K(+), and Cl(-)
      excretion, and blood pressure were similar in sgk1(-/-) and sgk1(+/+) mice.
      Addition of 10% fructose to drinking water increased fluid intake and urinary
      flow rate in both genotypes, and did not significantly alter urinary Na(+), K(+),
      and Cl(-) output in either genotype. Additional high NaCl diet (4% NaCl) did not
      significantly alter fluid intake and urine volume but markedly increased urinary
      output of Na(+) and Cl(-), approaching values significantly (P < 0.05) larger in
      sgk1(-/-) than in sgk1(+/+) mice (Na(+): 2,572 +/- 462 vs. 1,428 +/- 236; Cl(-):
      2,364 +/- 388 vs. 1,379 +/- 225 micromol/24 h). Blood pressure was similar in
      sgk1(+/+) and sgk1(-/-) mice at control diet or fructose alone but increased only
      in sgk1(+/+) mice (115 +/- 1 vs. 103 +/- 0.7 mmHg, P < 0.05) after combined
      fructose and high-salt intake. Acute intravenous insulin infusion (during glucose
      clamp) caused antinatriuresis in sgk1(+/+) mice, an effect significantly blunted
      in sgk1(-/-) mice. The observations reveal a pivotal role of SGK1 in insulin
      mediated sodium retention and the salt-sensitizing hypertensive effect of high
      fructose intake.

PMID- 16284090
TI  - Metabolic syndrome increases endogenous carbon monoxide production to promote
      hypertension and endothelial dysfunction in obese Zucker rats.
AB  - Vascular heme oxygenase (HO) metabolizes heme to form carbon monoxide (CO).
      Increased heme-derived CO inhibits nitric oxide synthase and can contribute to
      hypertension via endothelial dysfunction in Dahl salt-sensitive rats. Obese
      Zucker rats (ZR) are models of metabolic syndrome. This study tests the
      hypothesis that endogenous CO formation is increased and contributes to
      hypertension and endothelial dysfunction in obese ZR. Awake obese ZR showed
      increased respiratory CO excretion, which was lowered by HO inhibitor
      administration [zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) 25 micromol.kg(
      1).24 h(-1) ip]. In awake obese ZR, chronically instrumented with femoral
      arterial catheters, blood pressure was elevated but was decreased by the HO
      inhibitor ZnDPBG. Body weight, blood glucose, glycated hemoglobin, plasma
      insulin, total and LDL cholesterol, oxidized LDL, and triglyceride levels were
      elevated in obese ZR, and, except for LDL cholesterol, were unchanged by HO
      inhibition. Total HO-1 protein levels were not different between lean and obese
      ZR aortas. In vitro experiments used isolated skeletal muscle arterioles with
      constant pressure and no flow, or constant midpoint, but altered endpoint
      pressures to establish graded levels of luminal flow. In obese ZR arterioles,
      responses to ACh and flow were attenuated. Acute in vitro pretreatment with an HO
      inhibitor, chromium mesoporphyrin, enhanced ACh and flow-induced dilation and
      abolished the differences between groups. Furthermore, exogenous CO prevented the
      restoration of flow-induced dilation by the HO inhibitor in obese ZR arterioles.
      These results suggest that HO-derived CO production is increased and promotes
      hypertension and arteriolar endothelial dysfunction in obese ZR with metabolic
      syndrome independent of affecting metabolic parameters.

PMID- 16284091
TI  - Defending body mass during food restriction in Acomys russatus: a desert rodent
      that does not store food.
AB  - Golden spiny mice, which inhabit rocky deserts and do not store food, must
      therefore employ physiological means to cope with periods of food shortage. Here
      we studied the physiological means used by golden spiny mice for conserving
      energy during food restriction and refeeding and the mechanism by which food
      consumption may influence thermoregulatory mechanisms and metabolic rate. As
      comparison, we studied the response to food restriction of another rocky desert
      rodent, Wagner's gerbil, which accumulates large seed caches. Ten out of 12 food
      restricted spiny mice (resistant) were able to defend their body mass after an
      initial decrease, as opposed to Wagner's gerbils (n = 6). Two of the spiny mice
      (nonresistant) kept losing weight, and their food restriction was halted. In four
      resistant and two nonresistant spiny mice, we measured heart rate, body
      temperature, and oxygen consumption during food restriction. The resistant spiny
      mice significantly (P < 0.05) reduced energy expenditure and entered daily
      torpor. The nonresistant spiny mice did not reduce their energy expenditure. The
      gerbils' response to food restriction was similar to that of the nonresistant
      spiny mice. Resistant spiny mice leptin levels dropped significantly (n = 6, P <
      0.05) after 24 h of food restriction, and continued to decrease throughout food
      restriction, as did body fat. During refeeding, although the golden spiny mice
      gained fat, leptin levels were not correlated with body mass (r(2) = 0.014). It
      is possible that this low correlation allows them to continue eating and
      accumulate fat when food is plentiful.

PMID- 16284092
TI  - Bioinformatic analysis of the genomes of the cyanobacteria Synechocystis sp. PCC
      6803 and Synechococcus elongatus PCC 7942 for the presence of peroxiredoxins and
      their transcript regulation under stress.
AB  - The genomes of the cyanobacteria Synechocystis sp. PCC 6803 and Synechococcus
      elongatus PCC 7942 encode five and six open reading frames (ORFs), respectively,
      with similarity to peroxide-detoxifying peroxiredoxins (Prx). In addition to one
      highly conserved gene each for 2-Cys Prx and 1-Cys Prx, the Synechocystis sp. PCC
      6803 genome contains one TypeII Prx and two PrxQ-like ORFs, while Synechococcus
      elongatus PCC 7942 has four PrxQ-like ORFs. The transcript regulation of all
      these bioinformatically identified genes was analysed under selected stress
      conditions, i.e. light limitation and light stress, hydrogen peroxide,
      methylviologen, salinity, as well as nitrogen- and iron-deficiency. The results
      on specific time- and stress-dependent regulation of transcript amounts suggest
      conserved as well as variable functions of these putative Prx-s in antioxidant
      defence. The results are discussed in the context of evolution and physiological
      function, particularly in relation to photosynthesis.

PMID- 16284093
TI  - Hyperhomocysteinemia, endothelial nitric oxide synthase polymorphism, and risk of
      coronary artery disease.
AB  - BACKGROUND: Hyperhomocysteinemia is an independent, graded risk factor for
      coronary artery disease (CAD). The G894T variant of endothelial nitric oxide
      synthase (eNOS) was postulated to be associated with hyperhomocysteinemia and
      could influence individual susceptibility to CAD. The aims of this study were to
      investigate (a) the relationship of the eNOS G894T polymorphism with the presence
      and the severity of CAD and (b) the possible relationship between
      hyperhomocysteinemia and the eNOS G894T variant for the risk of CAD severity in a
      Tunisian population. METHODS: We used PCR with restriction fragment length
      polymorphism analysis to detect the G894T variant of the eNOS gene in 100
      patients with CAD and 120 healthy controls. The severity of CAD was expressed by
      the number of affected vessels. Total plasma homocysteine concentrations were
      determined by direct chemiluminescence assay. RESULTS: The frequencies of the
      eNOS GG, GT, and TT genotypes in the CAD group were significantly different from
      those in the control group (45%, 44%, and 11% vs 60%, 35.8% and 4.2%,
      respectively; P = 0.035). There was no association between the eNOS G894T
      genotype frequencies and the number of stenosed vessels (P = 0.149). In the CAD
      group, the coexistence of the 894 GT or TT genotypes and hyperhomocysteinemia led
      to an increased risk of CAD severity. CONCLUSION: The G894T polymorphism of the
      eNOS gene is associated with the presence of CAD, and in conjunction with
      hyperhomocysteinemia, increased the risk of CAD severity in a Tunisian
      population.

PMID- 16284094
TI  - Trichostatin A sensitises rheumatoid arthritis synovial fibroblasts for TRAIL
      induced apoptosis.
AB  - BACKGROUND: Histone acetylation/deacetylation has a critical role in the
      regulation of transcription by altering the chromatin structure. OBJECTIVE: To
      analyse the effect of trichostatin A (TSA), a streptomyces metabolite which
      specifically inhibits mammalian histone deacetylases, on TRAIL-induced apoptosis
      of rheumatoid arthritis synovial fibroblasts (RASF). METHODS: Apoptotic cells
      were detected after co-treatment of RASF with TRAIL (200 ng/ml) and TSA (0.5, 1,
      and 2 micromol/l) by flow cytometry using propidium iodide/annexin-V-FITC
      staining. Cell proliferation was assessed using the MTS proliferation test.
      Induction of the cell cycle inhibitor p21Waf/Cip1 by TSA was analysed by western
      blot. Expression of the TRAIL receptor-2 (DR5) on the cell surface of RASF was
      analysed by flow cytometry. Levels of soluble TRAIL were measured in synovial
      fluid of patients with RA and osteoarthritis (OA) by ELISA. RESULTS: Co-treatment
      of the cells with TSA and TRAIL induced cell death in a synergistic and dose
      dependent manner, whereas TRAIL and TSA alone had no effect or only a modest
      effect. RASF express DR5 (TRAIL receptor 2), but treatment of the cells with TSA
      for 24 hours did not change the expression level of DR5, as it is shown for
      cancer cells. TSA induced cell cycle arrest in RASF through up regulation of
      p21Waf1/Cip1. Levels of soluble TRAIL were significantly higher in RA than in OA
      synovial fluids. CONCLUSION: Because TSA sensitises RASF for TRAIL-induced
      apoptosis, it is concluded that TSA discloses sensitive sites in the cascade of
      TRAIL signalling and may represent a new principle for the treatment of RA.

PMID- 16284095
TI  - Hand bone loss in early undifferentiated arthritis: evaluating bone mineral
      density loss before the development of rheumatoid arthritis.
AB  - OBJECTIVES: (1) To examine the change in regional bone mineral density (BMD),
      including the hands, and assess its role as a predictor of outcome in patients
      presenting with an early undifferentiated inflammatory arthritis; (2) to examine
      for associations with the changes in hand BMD. METHODS: 74 patients with
      undifferentiated hand arthritis of less than 12 months' duration were examined at
      baseline and then at three, six, and 12 months follow up, including BMD
      measurement of the femoral neck, spine (L2-4), and the whole hands using dual
      energy absorptiometry (DXA). RESULTS: During the study, 13 patients were
      diagnosed as having rheumatoid arthritis, 19 as having inflammatory non
      rheumatoid joint disorders, and 42 as having non-inflammatory joint disorders. At
      the femoral neck and lumbar spine no significant bone loss was seen in any of the
      three subgroups. At the 12 months follow up the mean (95% confidence interval)
      hand BMD loss in the patients with rheumatoid arthritis was -4.27% (-1.41 to 
      7.13); in the inflammatory non-rheumatoid group, -0.49% (-1.33 to +0.35); and in
      the non-inflammatory joint disorder group, -0.87% (-1.51 to -0.23). In a
      multivariate linear regression model (including age, rheumatoid factor, mean C
      reactive protein, mean HAQ score, and cumulative glucocorticoid dose), only mean
      C reactive protein (p<0.001) and rheumatoid factor (p = 0.04) were independently
      associated with change in hand BMD during follow up. CONCLUSIONS: Hand DXA
      provides a very sensitive tool for measuring bone loss in early rheumatoid
      arthritis and may be useful in identifying patients at high risk of developing
      progressive disease. Further studies are needed to evaluate the role of hand bone
      loss as a prognostic factor and outcome measure in rheumatoid arthritis.

PMID- 16284096
TI  - Urinary CTX-II and glucosyl-galactosyl-pyridinoline are associated with the
      presence and severity of radiographic knee osteoarthritis in men.
AB  - OBJECTIVE: To investigate the association between biochemical markers of bone,
      cartilage, and synovial turnover with the presence and severity of knee
      osteoarthritis (OA) in men. METHODS: 176 men aged 59-70 years from the MRC
      Hertfordshire Cohort were studied. Weightbearing anteroposterior and lateral
      semiflexed radiographs were taken of both knees. A lifestyle questionnaire
      including basic demographic details and a questionnaire detailing knee pain was
      completed. This random sample was stratified based on the Kellgren and Lawrence
      (K&L) score, and the following biochemical markers were analysed: serum
      osteocalcin, serum C-terminal crosslinked telopeptide of type I collagen (CTX-I),
      urinary C-terminal crosslinked telopeptide of type II collagen (CTX-II), and
      urinary glucosyl-galactosyl-pyridinoline (Glc-Gal-Pyd). RESULTS: Age, body mass
      index (BMI), social class, smoking, and alcohol consumption were similar across
      K&L grades. Only one subject had a grade 4 K&L score, and was amalgamated with
      grade 3 subjects. A strong significant association was found between the presence
      of knee OA and urinary CTX-II and urinary Glc-Gal-Pyd (p=0.0001 and p=0.009),
      which persisted after adjustment for age and BMI. A significant positive
      association was also found between urinary CTX-II and urinary Glc-Gal-Pyd and the
      severity of K&L grade, joint space narrowing, and osteophytes scores, which
      persisted after adjustment for age and BMI. No associations between the presence
      and severity of knee OA were found for serum CTX-I or serum osteocalcin.
      CONCLUSIONS: Urinary CTX-II and Glc-Gal-Pyd, but not systemic markers of bone
      turnover, are strongly associated with disease severity and the presence of OA at
      the tibiofemoral and patellofemoral joints in men.

PMID- 16284098
TI  - TNFalpha polymorphisms and risk of psoriatic arthritis.
AB  - BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a cytokine of critical
      importance in psoriatic arthritis. OBJECTIVES: (1) To examine the association
      between TNFalpha promoter gene polymorphisms and psoriatic arthritis in two well
      characterised Canadian populations with the disease; (2) to carry out a meta
      analysis of all TNFalpha association studies in white psoriatic arthritis
      populations. METHODS: DNA samples were genotyped for five TNF variants by time of
      flight mass spectrometry using the Sequenom platform. All five single nucleotide
      polymorphisms were in the 5' flanking region of TNFalpha gene at the following
      positions: -1031 (T-->C), -863 (C-->A), -857 (C-->T), -308 (G-->A), and -238 (G-
      >A). Primary analyses were based on logistic regression. Summary estimates of
      disease/genotype relations from several studies were derived from random effects
      meta-analyses. RESULTS: 237 psoriatic arthritis subjects and 103 controls from
      Newfoundland and 203 psoriatic arthritis subjects and 101 controls from Toronto
      were studied. A combined analysis of data from both populations, showed a
      significant association between disease status and the -238(A) variant (p=0.01).
      The meta-analysis estimate for the -238(A) TNFalpha variant in eight psoriatic
      arthritis populations was also significant (odds ratio=2.29 (95% confidence
      interval, 1.48 to 3.55)). CONCLUSIONS: Analysis of TNFalpha variants in psoriatic
      arthritis populations shows that the -238 (A) variant is a significant risk
      factor for this disease.

PMID- 16284097
TI  - Lymphoma and other malignancies in primary Sjogren's syndrome: a cohort study on
      cancer incidence and lymphoma predictors.
AB  - OBJECTIVES: To assess the risk of lymphoproliferative disease or other malignancy
      (standardised incidence ratios (SIRs)), in patients with primary Sjogren's
      syndrome according to the American-European Consensus Criteria (AECC), compared
      with patients with sicca syndrome (non-AECC) and the background population. To
      identify predictors of malignancy and describe lymphoma types and survival
      probabilities. METHODS: A linked register study using information from the Malmo
      Primary SS Register, Swedish Cancer Register, and Cause-of-Death Register for
      calculation of SIRs was carried out. Detected lymphomas were reclassified
      according to the WHO classification. Cox regression analysis was used to study
      the predictive value of clinical, laboratory, and histological findings at the
      time of diagnosis. RESULTS: 507 patients with a median follow up of 8 years
      (range 1 month to 19 years) were included. SIRs (95% confidence interval (CI))
      for malignancies in total and for non-Hodgkin's lymphomas (NHL) were 1.42 (0.98
      to 2.00) and 15.57 (7.77 to 27.85), respectively, in those fulfilling the AECC (n
      = 286). In non-AECC sicca patients (n = 221) SIR for malignancy of any kind was
      0.77 (0.41 to 1.32); no lymphoproliferative neoplasms were detected. Significant
      predictors of lymphoproliferative disease were purpura/skin vasculitis (hazard
      ratio (HR) = 4.64, 95% CI 1.13 to 16.45), low complement factor C3 (HR = 6.18,
      95% CI 1.57 to 24.22), low C4 (HR = 9.49, 95% CI 1.94 to 46.54), CD4+ T
      lymphocytopenia (HR = 8.14, 95% CI 2.10 to 31.53), and a low CD4+/CD8+ T cell
      ratio < or = 0.8 (HR = 10.92, 95% CI 2.80 to 41.83). 7/12 (58%) NHLs were diffuse
      large B cell lymphomas. CONCLUSION: A 16-fold increased risk for development of
      NHL was found. CD4+ T lymphocytopenia is an additional strong risk factor for
      developing lymphoma.

PMID- 16284100
TI  - Multiplex PCR for rapid detection of genes encoding CTX-M extended-spectrum
      (beta)-lactamases.

PMID- 16284099
TI  - The association between periodontal disease and joint destruction in rheumatoid
      arthritis extends the link between the HLA-DR shared epitope and severity of bone
      destruction.
AB  - OBJECTIVE: To evaluate a possible association between wrist and periodontal
      destruction in rheumatoid arthritis, and between periodontal destruction, dry
      mouth, and labial salivary gland biopsy and the contribution of genetic factors
      (the shared epitope (SE) and IL1B (+3954) or TNFA (-238 or -308) gene
      polymorphisms). METHODS: 147 patients with rheumatoid arthritis were enrolled.
      Periodontal damage was defined according to the Hugoson and Jordan criteria on
      panoramic dental x rays. Typing for the SE and cytokine polymorphisms was
      undertaken by enzyme linked oligosorbent assay. Odds ratios (OR), relative risk
      (RR), and chi2 values were calculated to quantify associations. RESULTS: An
      association was observed between wrist and periodontal bone destruction
      (chi2=11.82; p<0.001): 63 patients had both wrist and periodontal destruction, 31
      had wrist destruction alone, 20 had periodontal destruction alone, and 33 had no
      destruction at either site. An association was seen between a positive labial
      salivary gland biopsy and periodontal bone destruction (RR=2.73 (95% CI, 1.35 to
      5.51), p<0.01, n=41) or wrist bone destruction (RR=4.52 (1.96 to 10.45), p<0.001,
      n=41). The SE was associated with wrist bone destruction (OR=2.5 (1.16 to 5.42),
      p<0.05) and periodontal bone destruction (OR=2.2 (1.04 to 4.84), p<0.05). No
      association was found between the selected cytokine polymorphisms and bone
      destruction. CONCLUSIONS: A strong association was found between wrist and
      periodontal bone destruction. The destruction risk was further increased in
      patients with sicca syndrome. The SE appears to be a severity genetic marker for
      both wrist and periodontal bone destruction.

PMID- 16284101
TI  - Occurrence of extended-spectrum (beta)-lactamases and plasmid-mediated AmpC
      (beta)-lactamases among Korean isolates of Proteus mirabilis.

PMID- 16284102
TI  - In vitro activity of a new triazole BAL4815, the active component of BAL8557 (the
      water-soluble prodrug), against Aspergillus spp.
AB  - OBJECTIVES: BAL4815 is the active component of the antifungal triazole agent
      BAL8557 (the water-soluble prodrug). We compared the in vitro activity of BAL4815
      with that of itraconazole, voriconazole, caspofungin and amphotericin B against
      118 isolates of Aspergillus comprising four different species (fumigatus,
      terreus, flavus and niger); the isolates were pre-selected to include 16 isolates
      demonstrating in vitro resistance to other agents. METHODS: Susceptibilities were
      determined for BAL4815, amphotericin B, itraconazole and voriconazole using the
      microdilution plate modification of the NCCLS M38-A method with RPMI 1640
      buffered to pH 7.0 with MOPS; for caspofungin the method was modified using
      incubation in a gas mixture of 1% O2/5% CO2/94% N2 to aid reading. MFCs (> or
      =99% kill) were also determined for all drugs other than caspofungin. RESULTS:
      For all isolates, geometric mean (GM) MIC values and ranges (in mg/L) were:
      BAL4815, 0.620 and 0.125-2.0; itraconazole, 0.399 and 0.063->8.0; voriconazole,
      0.347 and 0.125-8.0; caspofungin, 0.341 and 0.125-4.0; amphotericin B, 0.452 and
      0.06-4.0. No significant differences in susceptibility to BAL4815 were seen
      between species and in contrast to itraconazole no isolates demonstrated MICs
      >2.0 mg/L. For all isolates, GM MFC values and ranges (in mg/L) were: BAL4815,
      1.68 and 0.25->8.0; itraconazole, 1.78 and 0.06->8.0; voriconazole, 1.09 and 0.25
      >8.0; amphotericin B, 0.98 and 0.25->4.0. CONCLUSIONS: BAL4815 demonstrated
      promising antifungal activity against all four Aspergillus species in vitro
      including strains resistant to itraconazole, caspofungin or amphotericin B.

PMID- 16284103
TI  - First outbreak of multidrug-resistant Klebsiella pneumoniae carrying blaVIM-1 and
      blaSHV-5 in a French university hospital.
AB  - OBJECTIVES: We studied eight imipenem-resistant isolates of Klebsiella pneumoniae
      involved in an outbreak in a French teaching hospital. METHODS: The eight
      isolates were recovered from clinical specimens or rectal swabs. Antibiotic
      susceptibilities were determined using standard agar diffusion and dilution
      methods including synergy tests. PFGE was used to study the relatedness of
      isolates. Genes encoding beta-lactamases were characterized by transfer assays,
      specific amplification and cloning. RESULTS: The eight isolates were closely
      related by PFGE analysis and highly related to a K. pneumoniae strain from
      Greece. They were highly resistant to beta-lactams, including aztreonam and
      imipenem (MIC > or =32 mg/L), and were positive by the imipenem-EDTA disc synergy
      test. Isolates were also resistant to aminoglycosides, newer quinolones and
      sulfamethoxazole, and showed an intermediate level of resistance to tetracycline.
      VIM-1 and SHV-5 beta-lactamases were revealed in all isolates by PCR. The
      analysis of plasmid contents of Escherichia coli DH10B electroporants expressing
      the VIM-1 beta-lactamase or the SHV-5 beta-lactamase confirmed that the two
      enzymes were coded by two different plasmids. The bla(VIM-1) gene was part of a
      class 1 integron that also included aac6, dhfrI and aadA genes and was similar to
      those reported from strains isolated in Greece. CONCLUSIONS: This study confirms
      the potential risk of spread of multiresistant bacteria with international
      transfer of patients.

PMID- 16284104
TI  - Costameres, focal adhesions, and cardiomyocyte mechanotransduction.
AB  - Mechanotransduction refers to the cellular mechanisms by which load-bearing cells
      sense physical forces, transduce the forces into biochemical signals, and
      generate appropriate responses leading to alterations in cellular structure and
      function. This process affects the beat-to-beat regulation of cardiac performance
      but also affects the proliferation, differentiation, growth, and survival of the
      cellular components that comprise the human myocardium. This review focuses on
      the experimental evidence indicating that the costamere and its structurally
      related structure the focal adhesion complex are critical cytoskeletal elements
      involved in cardiomyocyte mechanotransduction. Biochemical signals originating
      from the extracellular matrix-integrin-costameric protein complex share many
      common features with those signals generated by growth factor receptors. The
      roles of key regulatory kinases and other muscle-specific proteins involved in
      mechanotransduction and growth factor signaling are discussed, and issues
      requiring further study in this field are outlined.

PMID- 16284105
TI  - Effect of p38 MAP kinase on cellular events during ischemia and reperfusion:
      possible therapy.

PMID- 16284106
TI  - Temporal gradients in shear, but not spatial gradients, stimulate ERK1/2
      activation in human endothelial cells.
AB  - We have previously demonstrated temporal gradients in shear stress stimulate
      endothelial cell proliferation, whereas spatial gradients do not. In the present
      study, the extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway was
      investigated as a possible mediator for the promitogenic effect of temporal
      gradients. The sudden expansion flow chamber (SEFC) model was used to
      differentiate the effect of temporal gradients in shear from that of spatial
      gradients on ERK1/2 activation in human umbilical vein endothelial cells (HUVEC).
      ERK1/2 activation in the SEFC was not significantly different from control when
      HUVEC were exposed to spatial gradients alone. When a single temporal impulse was
      superimposed on spatial gradients, ERK1/2 activation was stimulated 330%
      (relative to spatial alone) within the region of spatial gradients. Inhibition of
      the ERK1/2 pathway with U-0126 abolished all effects of temporal gradients. To
      further separate temporal and spatial gradients, a conventional parallel plate
      flow chamber was utilized. Acute exposure to oscillations in flow at a frequency
      of 1 Hz stimulated ERK1/2 activation 620 +/- 88% relative to control, whereas a
      single impulse of flow increased ERK1/2 activation 166 +/- 19%. Flow without the
      temporal component did not significantly activate ERK1/2. These results suggest
      that the ERK1/2 pathway directly mediates the promitogenic effects of temporal
      gradients in shear stress.

PMID- 16284107
TI  - Activation of inward rectifier K+ channels by hypoxia in rabbit coronary arterial
      smooth muscle cells.
AB  - We examined the effects of acute hypoxia on Ba2+-sensitive inward rectifier K+
      (K(IR)) current in rabbit coronary arterial smooth muscle cells. The amplitudes
      of K(IR) current was definitely higher in the cells from small-diameter (<100
      microm) coronary arterial smooth muscle cells (SCASMC, -12.8 +/- 1.3 pA/pF at 
      140 mV) than those in large-diameter coronary arterial smooth muscle cells (>200
      microm, LCASMC, -1.5 +/- 0.1 pA pF(-1)). Western blot analysis confirmed that
      Kir2.1 protein was expressed in SCASMC but not LCASMC. Hypoxia activated much
      more KIR currents in symmetrical 140 K+. This effect was blocked by the adenylyl
      cyclase inhibitor SQ-22536 (10 microM) and mimicked by forskolin (10 microM) and
      dibutyryl-cAMP (500 microM). The production of cAMP in SCASMC increased 5.7-fold
      after 6 min of hypoxia. Hypoxia-induced increase in KIR currents was abolished by
      the PKA inhibitors, Rp-8-(4-chlorophenylthio)-cAMPs (10 microM) and KT-5720 (1
      microM). The inhibition of G protein with GDPbetaS (1 mM) partially reduced
      (approximately 50%) the hypoxia-induced increase in KIR currents. In Langendorff
      perfused rabbit hearts, hypoxia increased coronary blood flow, an effect that was
      inhibited by Ba2+. In summary, hypoxia augments the KIR currents in SCASMC via
      cAMP- and PKA-dependent signaling cascades, which might, at least partly, explain
      the hypoxia-induced coronary vasodilation.

PMID- 16284108
TI  - Advances in sleep-disordered breathing.
AB  - Since the original clarification of the obstructive nature of obstructive sleep
      apnea (OSA) in 1965, much has been learned about the disorder. It is a condition
      with a high prevalence with obesity as a major risk factor. It aggregates in
      families, a relationship that is not simply explained by obesity. Premenopausal
      women are relatively protected from the disorder because OSA is uncommon in this
      group. Its prevalence in women rises after menopause. Although OSA is a risk
      factor for excessive sleepiness, there is developing evidence that it is also a
      risk factor for hypertension, acute cardiovascular events, and insulin
      resistance. The first line of therapy is nasal continuous positive airway
      pressure. Data as to the efficacy of continuous positive airway pressure in
      severe OSA have come from randomized, placebo-controlled clinical trials with the
      endpoints being sleepiness, quality of life, and 24-h ambulatory blood pressure.
      Data are currently less convincing for treatment outcomes in mild to moderate
      OSA, and new clinical trials to assess outcomes in this group are underway. Thus,
      even though this field only began toward the end of the first century of the
      American Thoracic Society, substantial progress has been made, and OSA has
      increasingly emerged as a major public health concern.

PMID- 16284116
TI  - Directed differentiation of neural cells to hypothalamic dopaminergic neurons.
AB  - Hypothalamic neurons play a key role in homeostasis, yet little is known about
      their differentiation. Here, we demonstrate that Shh and Bmp7 from the adjacent
      prechordal mesoderm govern hypothalamic neural fate, their sequential action
      controlling hypothalamic dopaminergic neuron generation in a Six3-dependent
      manner. Our data suggest a temporal distinction in the requirement for the two
      signals. Shh acts early to specify dopaminergic neurotransmitter phenotype.
      Subsequently, Bmp7 acts on cells that are ventralised by Shh, establishing
      aspects of hypothalamic regional identity in late-differentiating/postmitotic
      cells. The concerted actions of Shh and Bmp7 can direct mouse embryonic stem cell
      derived neural progenitor cells to a hypothalamic dopaminergic fate ex vivo.

PMID- 16284117
TI  - Gli3 acts as a repressor downstream of Ihh in regulating two distinct steps of
      chondrocyte differentiation.
AB  - During endochondral ossification, the secreted growth factor Indian hedgehog
      (Ihh) regulates several differentiation steps. It interacts with a second
      secreted factor, parathyroid hormone-related protein (PTHrP), to regulate the
      onset of hypertrophic differentiation, and it regulates chondrocyte proliferation
      and ossification of the perichondrium independently of PTHrP. To investigate how
      the Ihh signal is translated in the different target tissues, we analyzed the
      role of the zinc-finger transcription factor Gli3, which acts downstream of
      hedgehog signals in other organs. Loss of Gli3 in Ihh mutants restores
      chondrocyte proliferation and delays the accelerated onset of hypertrophic
      differentiation observed in Ihh-/- mutants. Furthermore the expression of the Ihh
      target genes patched (Ptch) and PTHrP is reactivated in Ihh-/-;Gli3-/- mutants.
      Gli3 seems thus to act as a strong repressor of Ihh signals in regulating
      chondrocyte differentiation. In addition, loss of Gli3 in mice that overexpress
      Ihh in chondrocytes accelerates the onset of hypertrophic differentiation by
      reducing the domain and possibly the level of PTHrP expression. Careful analysis
      of chondrocyte differentiation in Gli3-/- mutants revealed that Gli3 negatively
      regulates the differentiation of distal, low proliferating chondrocytes into
      columnar, high proliferating cells. Our results suggest a model in which the
      Ihh/Gli3 system regulates two distinct steps of chondrocyte differentiation: (1)
      the switch from distal into columnar chondrocytes is repressed by Gli3 in a PTHrP
      independent mechanism; (2) the transition from proliferating into hypertrophic
      chondrocytes is regulated by Gli3-dependent expression of PTHrP. Furthermore, by
      regulating distal chondrocyte differentiation, Gli3 seems to position the domain
      of PTHrP expression.

PMID- 16284109
TI  - The effects of volatile salivary acids and bases on exhaled breath condensate pH.
AB  - RATIONALE: Recent studies have reported acidification of exhaled breath
      condensate (EBC) in inflammatory lung diseases. This phenomenon, designated
      "acidopnea," has been attributed to airway inflammation. OBJECTIVES: To determine
      whether salivary acids and bases can influence EBC pH in chronic obstructive
      pulmonary disease (COPD). METHODS: Measurements were made of pH, electrolytes,
      and volatile bases and acids in saliva and EBC equilibrated with air in 10
      healthy subjects and 10 patients. RESULTS: The average EBC pH in COPD was reduced
      (normal, 7.24 +/- 0.24 SEM; range, 6.11-8.34; COPD, 6.67 +/- 0.18; range, 5.74
      7.64; p = 0.079). EBCs were well buffered by NH(4)(+)/NH(3) and CO(2)/HCO(3)(-)
      in all but four patients, who had NH(4)(+) concentrations under 60 micromol/L,
      and acetate concentrations that approached or exceeded those of NH(4)(+). Saliva
      contained high concentrations of acetate (approximately 6,000 micromol/L) and
      NH(4)(+) (approximately 12,000 micromol/L). EBC acetate increased and EBC
      NH(4)(+) decreased when salivary pH was low, consistent with a salivary source
      for these volatile constituents. Nonvolatile acids did not play a significant
      role in determining pH of condensates because of extreme dilution of respiratory
      droplets by water vapor (approximately 1:12,000). Transfer of both acetic acid
      and NH(3) from the saliva to the EBC was in the gas phase rather than droplets.
      CONCLUSIONS: EBC acidification in COPD can be affected by the balance of volatile
      salivary acids and bases, suggesting that EBC pH may not be a reliable marker of
      airway acidification. Salivary acidification may play an important role in
      acidopnea.

PMID- 16284118
TI  - Evolutionarily conserved domains required for activation and repression functions
      of the Drosophila Hox protein Ultrabithorax.
AB  - While testing the functions of deletion mutants in the Hox protein Ultrabithorax
      (Ubx), we found that the embryonic repression function of Ubx on Distal-less
      transcription in limb primordia is highly concentration dependent. The steep
      sigmoidal relationship between in vivo Ubx concentration and Distal-less
      repression is dependent on the Ubx YPWM motif. This suggests that Ubx
      cooperatively assembles a multi-protein repression complex on Distal-less
      regulatory DNA with the YPWM motif as a key protein-protein interface in this
      complex. Our deletion mutants also provide evidence for a transcriptional
      activation domain in the N-terminal 19 amino acids of Ubx. This proposed
      activation domain contains a variant of the SSYF motif that is found at the N
      termini of many Hox proteins, and is conserved in the activation domain of
      another Hox protein, Sex combs reduced. These results suggest that the N-terminal
      region containing the SSYF motif has been conserved in many Hox proteins for its
      role in transcriptional activation.

PMID- 16284119
TI  - Steroid-dependent modification of Hox function drives myocyte reprogramming in
      the Drosophila heart.
AB  - In the Drosophila larval cardiac tube, aorta and heart differentiation are
      controlled by the Hox genes Ultrabithorax (Ubx) and abdominal A (abdA),
      respectively. There is evidence that the cardiac tube undergoes extensive
      morphological and functional changes during metamorphosis to form the adult
      organ, but both the origin of adult cardiac tube myocytes and the underlying
      genetic control have not been established. Using in vivo time-lapse analysis, we
      show that the adult fruit fly cardiac tube is formed during metamorphosis by the
      reprogramming of differentiated and already functional larval cardiomyocytes,
      without cell proliferation. We characterise the genetic control of the process,
      which is cell autonomously ensured by the modulation of Ubx expression and AbdA
      activity. Larval aorta myocytes are remodelled to differentiate into the
      functional adult heart, in a process that requires the regulation of Ubx
      expression. Conversely, the shape, polarity, function and molecular
      characteristics of the surviving larval contractile heart myocytes are profoundly
      transformed as these cells are reprogrammed to form the adult terminal chamber.
      This process is mediated by the regulation of AbdA protein function, which is
      successively required within these persisting myocytes for the acquisition of
      both larval and adult differentiated states. Importantly, AbdA specificity is
      switched at metamorphosis to induce a novel genetic program that leads to
      differentiation of the terminal chamber. Finally, the steroid hormone ecdysone
      controls cardiac tube remodelling by impinging on both the regulation of Ubx
      expression and the modification of AbdA function. Our results shed light on the
      genetic control of one in vivo occurring remodelling process, which involves a
      steroid-dependent modification of Hox expression and function.

PMID- 16284120
TI  - Zebrafish vps33b, an ortholog of the gene responsible for human arthrogryposis
      renal dysfunction-cholestasis syndrome, regulates biliary development downstream
      of the onecut transcription factor hnf6.
AB  - Arthrogryposis-renal dysfunction-cholestasis syndrome (ARC) is a rare cause of
      cholestasis in infants. Causative mutations in VPS33B, a gene that encodes a
      Class C vacuolar sorting protein, have recently been reported in individuals with
      ARC. We have identified a zebrafish vps33b-ortholog that is expressed in
      developing liver and intestine. Knockdown of vps33b causes bile duct paucity and
      impairs intestinal lipid absorption, thus phenocopying digestive defects
      characteristic of ARC. By contrast, neither motor axon nor kidney epithelial
      defects typically seen in ARC could be identified in vps33b-deficient larvae.
      Biliary defects in vps33b-deficient zebrafish larvae closely resemble the bile
      duct paucity associated with knockdown of the onecut transcription factor hnf6.
      Consistent with this, reduced vps33b expression was evident in hnf6-deficient
      larvae and in larvae with mutation of vhnf1, a downstream target of hnf6.
      Zebrafish vhnf1, but not hnf6, increases vps33b expression in zebrafish embryos
      and in mammalian liver cells. Electrophoretic mobility shift assays suggest that
      this regulation occurs through direct binding of vHnf1 to the vps33b promoter.
      These findings identify vps33b as a novel downstream target gene of the
      hnf6/vhnf1 pathway that regulates bile duct development in zebrafish.
      Furthermore, they show that tissue-specific roles for genes that regulate
      trafficking of intracellular proteins have been modified during vertebrate
      evolution.

PMID- 16284121
TI  - Tbx1 expression in pharyngeal epithelia is necessary for pharyngeal arch artery
      development.
AB  - During embryonic life, the initially paired pharyngeal arch arteries (PAAs)
      follow a precisely orchestrated program of persistence and regression that leads
      to the formation of the mature aortic arch and great vessels. When this program
      fails, specific cardiovascular defects arise that may be life threatening or
      mild, according to the identity of the affected artery. Fourth PAA-derived
      cardiovascular defects occur commonly in DiGeorge syndrome and velocardiofacial
      syndrome (22q11DS), and in Tbx1(+/-) mice that model the 22q11DS cardiovascular
      phenotype. Tbx1 is expressed in pharyngeal mesoderm, endoderm and ectoderm, and,
      in addition, we show that it is expressed in precursors of the endothelial cells
      that line the PAAs, thus expanding the number of tissues in which Tbx1 is
      potentially required for fourth PAA development. In this study, we have used cell
      fate mapping and tissue-specific gene deletion, driven by six different Cre
      lines, to explore Tbx1 gene-dosage requirements in the embryonic pharynx for
      fourth PAA development. Through this approach, we have resolved the spatial
      requirements for Tbx1 in this process, and we show pharyngeal epithelia to be a
      critical tissue. We also thereby demonstrate conclusively that the role of Tbx1
      in fourth PAA development is cell non-autonomous.

PMID- 16284122
TI  - The serosal mesothelium is a major source of smooth muscle cells of the gut
      vasculature.
AB  - Most internal organs are situated in a coelomic cavity and are covered by a
      mesothelium. During heart development, epicardial cells (a mesothelium) move to
      and over the heart, undergo epithelial-mesenchymal transition (EMT), and
      subsequently differentiate into endothelial and vascular smooth muscle cells.
      This is thought to be a unique process in blood vessel formation. Still,
      structural and developmental similarities between the heart and gut led us to
      test the hypothesis that a conserved or related mechanism may regulate blood
      vessel development to the gut, which, similar to the heart, is housed in a
      coelomic cavity. By using a combination of molecular genetics, vital dye fate
      mapping, organ culture and immunohistochemistry, we demonstrate that the serosal
      mesothelium is the major source of vasculogenic cells in developing mouse gut.
      Our studies show that the gut is initially devoid of a mesothelium but that
      serosal mesothelial cells expressing the Wilm's tumor protein (Wt1) move to and
      over the gut. Subsequently, a subset of these cells undergoes EMT and migrates
      throughout the gut. Using Wt1-Cre genetic lineage marking of serosal cells and
      their progeny, we demonstrate that these cells differentiate to smooth muscle of
      all major blood vessels in the mesenteries and gut. Our data reveal a conserved
      mechanism in blood vessel formation to coelomic organs, and have major
      implications for our understanding of vertebrate organogenesis and vascular
      deficiencies of the gut.

PMID- 16284123
TI  - Dysfunctional cilia lead to altered ependyma and choroid plexus function, and
      result in the formation of hydrocephalus.
AB  - Cilia are complex organelles involved in sensory perception and fluid or cell
      movement. They are constructed through a highly conserved process called
      intraflagellar transport (IFT). Mutations in IFT genes, such as Tg737, result in
      severe developmental defects and disease. In the case of the Tg737orpk mutants,
      these pathological alterations include cystic kidney disease, biliary and
      pancreatic duct abnormalities, skeletal patterning defects, and hydrocephalus.
      Here, we explore the connection between cilia dysfunction and the development of
      hydrocephalus by using the Tg737orpk mutants. Our analysis indicates that cilia
      on cells of the brain ventricles of Tg737orpk mutant mice are severely malformed.
      On the ependymal cells, these defects lead to disorganized beating and impaired
      cerebrospinal fluid (CSF) movement. However, the loss of the cilia beat and CSF
      flow is not the initiating factor, as the pathology is present prior to the
      development of motile cilia on these cells and CSF flow is not impaired at early
      stages of the disease. Rather, our results suggest that loss of cilia leads to
      altered function of the choroid plexus epithelium, as evidenced by elevated
      intracellular cAMP levels and increased chloride concentration in the CSF. These
      data suggest that cilia function is necessary for regulating ion transport and
      CSF production, as well as for CSF flow through the ventricles.

PMID- 16284125
TI  - Molecular diversity in venom from the Australian Brown snake, Pseudonaja
      textilis.
AB  - Venom from the Australian elapid Pseudonaja textilis (Common or Eastern Brown
      snake), is the second most toxic snake venom known and is the most common cause
      of death from snake bite in Australia. This venom is known to contain a
      prothrombin activator complex, serine proteinase inhibitors, various
      phospholipase A2s, and pre- and postsynaptic neurotoxins. In this study, we
      performed a proteomic identification of the venom using two-dimensional gel
      electrophoresis, mass spectrometry, and de novo peptide sequencing. We identified
      most of the venom proteins including proteins previously not known to be present
      in the venom. In addition, we used immunoblotting and post-translational
      modification-specific enzyme stains and antibodies that reveal the complexity and
      regional diversity of the venom. Modifications observed include phosphorylation,
      gamma-carboxylation, and glycosylation. Glycoproteins were further characterized
      by enzymatic deglycosylation and by lectin binding specificity. The venom
      contains an abundance of glycoproteins with N-linked sugars that include
      glucose/mannose, N-acetylgalactosamine, N-acetylglucosamine, and sialic acids.
      Additionally there are multiple isoforms of mammalian coagulation factors that
      comprise a significant proportion of the venom. Indeed two of the identified
      proteins, a procoagulant and a plasmin inhibitor, are currently in development as
      human therapeutic agents.

PMID- 16284124
TI  - An integrated mass spectrometry-based proteomic approach: quantitative analysis
      of tandem affinity-purified in vivo cross-linked protein complexes (QTAX) to
      decipher the 26 S proteasome-interacting network.
AB  - We developed an integrated proteomic approach to decipher in vivo protein-protein
      interactions and applied this strategy to globally map the 26 S proteasome
      interaction network in yeast. We termed this approach QTAX for quantitative
      analysis of tandem affinity purified in vivo cross-linked (X) protein complexes.
      For this work, in vivo formaldehyde cross-linking was used to freeze both stable
      and transient interactions occurring in intact cells prior to lysis. To isolate
      cross-linked protein complexes with high purification efficiency under fully
      denaturing conditions, a new tandem affinity tag consisting of a hexahistidine
      sequence and an in vivo biotinylation signal was adopted for affinity-based
      purification. Tandem affinity purification after in vivo cross-linking was
      combined with tandem mass spectrometry coupled with a quantitative SILAC (stable
      isotope labeling of amino acids in cell culture) strategy to carry out
      unambiguous protein identification and quantification of specific protein
      interactions. Using this method, we captured and identified the full composition
      of yeast 26 S proteasome complex as well as the two known ubiquitin receptors,
      Rad23 and Dsk2. Quantitative mass spectrometry analysis allowed us to distinguish
      specific proteasome-interacting proteins (PIPs) from background proteins and led
      to the identification of a total of 64 potential PIPs of which 42 are novel
      interactions. Among the 64 putative specific PIPs, there are ubiquitin pathway
      components, ubiquitinated substrates, chaperones, and transcription and
      translation regulators, demonstrating the efficacy of the developed approach in
      capturing in vivo protein interactions. The method offers an advanced technical
      approach to elucidate the dynamic protein interaction networks of the proteasome
      and can find a wide range of applications in the studies of other macromolecular
      protein complex interaction networks.

PMID- 16284127
TI  - Intraductal papillary mucinous neoplasm of the pancreas: can benign lesions be
      differentiated from malignant lesions with multidetector CT?
AB  - Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a distinct
      clinicopathologic entity that is being recognized with increasing frequency. In
      25%-44% of IPMNs treated with surgical resection, associated invasive carcinoma
      has been reported. Surgical resection is the treatment of choice for most IPMNs.
      Preoperative determination of the presence or absence of associated invasive
      carcinoma is crucial. The prognosis is worse if there is associated invasive
      carcinoma; when invasive carcinoma is present, the surgical procedure may be
      modified to include resection of regional lymph nodes. The spectrum of
      appearances of IPMN, which includes adenoma, borderline lesion, and lesions with
      associated carcinoma in situ or invasive carcinoma, was studied with 16-section
      multidetector computed tomography (CT) and histologic correlation. CT was
      performed with dual-phase acquisition; the reconstructed images were reviewed on
      a workstation with axial scrolling and interactive multiplanar reformation and
      three-dimensional reformation techniques. Features predictive of invasive
      carcinoma in IPMN at CT and other imaging studies include involvement of the main
      pancreatic duct, marked dilatation of the main pancreatic duct, diffuse or
      multifocal involvement, the presence of a large mural nodule or solid mass, large
      size of the mass, and obstruction of the common bile duct.

PMID- 16284129
TI  - Cystic pancreatic lesions: a simple imaging-based classification system for
      guiding management.
AB  - Cystic lesions of the pancreas are increasingly being recognized due to the
      widespread use of cross-sectional imaging. The initial evaluation of a pancreatic
      cyst should be directed toward exclusion of a pseudocyst. Patients with
      pseudocysts generally have a history of acute or chronic pancreatitis, whereas
      those with cystic tumors most often lack such a history. Several types of cystic
      lesions are encountered in the pancreas. Because of morphologic overlap at
      imaging, accurate characterization of these lesions can be difficult. Computed
      tomography and magnetic resonance imaging are excellent modalities for both
      initial detection and characterization of cystic pancreatic lesions. An imaging
      classification system for these lesions has been proposed that is based on the
      morphologic features of the lesion. This system can be helpful in characterizing
      lesions, narrowing the differential diagnosis, and making decisions regarding the
      treatment of affected patients. Endoscopic ultrasonography-guided aspiration and
      biopsy is useful in cases that are indeterminate at cross-sectional imaging or
      that require observation.

PMID- 16284130
TI  - Surgical approach to gastroesophageal reflux disease: what the radiologist needs
      to know.
AB  - Gastroesophageal reflux disease (GERD) is defined as gastroesophageal reflux
      resulting in symptoms or in injury to the esophageal epithelium. Although the
      medical management of GERD has improved, an increasing number of laparoscopic
      antireflux surgical procedures are being performed. Barium studies, endoscopy,
      manometry, and pH monitoring are all integral components of preoperative
      evaluation. Barium swallow examination must allow critical evaluation of
      esophageal peristalsis, the presence and extent of gastroesophageal reflux, and
      complications including esophagitis, stricture, and Barrett esophagus. It is
      crucial to identify and characterize hiatal hernia and longitudinal stricture,
      which can result in a shortened esophagus. In such cases, it becomes necessary
      for the surgeon to incorporate an esophageal lengthening procedure prior to
      fundoplication; otherwise, poor surgical outcome is likely. Normal
      postfundoplication radiographic findings as well as postoperative complications
      (eg, tight wrap, perforation, abscess, complete or partial dehiscence, recurrent
      stricture, recurrent hernia, intrathoracic migration of the wrap) must also be
      recognized and clearly understood by the radiologist. Given the chronic nature
      and prevalence of symptomatic GERD and the increasing number of patients
      undergoing surgical intervention, it is imperative that the radiologist
      understand the pre- and postsurgical evaluation of affected patients.

PMID- 16284131
TI  - Abdominal wall hernias: imaging features, complications, and diagnostic pitfalls
      at multi-detector row CT.
AB  - Abdominal wall hernias are a common imaging finding in the abdomen and may be
      complicated by strangulation, incarceration, or trauma. Because of the risk of
      developing complications, most abdominal wall hernias are surgically repaired,
      even if asymptomatic. However, post-surgical complications are also common and
      include hernia recurrence, infected and noninfected fluid collections, and
      complications related to prosthetic material. Multi-detector row computed
      tomography (CT) with its multiplanar capabilities is particularly useful for the
      evaluation of unrepaired and surgically repaired abdominal wall hernias. Multi
      detector row CT provides exquisite anatomic detail of the abdominal wall, thereby
      allowing accurate identification of wall hernias and their contents,
      differentiation of hernias from other abdominal masses (tumors, hematomas,
      abscesses), and detection of pre- or postoperative complications. These findings
      improve the communication of imaging results to clinicians and help optimize
      treatment planning. Knowledge of multi-detector row CT findings in unrepaired and
      surgically repaired abdominal wall hernias and their complications is essential
      for making the correct diagnosis and may help guide clinical management.

PMID- 16284132
TI  - Acute epiploic appendagitis and its mimics.
AB  - Acute epiploic appendagitis most commonly manifests with acute lower quadrant
      pain. Its clinical features are similar to those of acute diverticulitis or, less
      commonly, acute appendicitis. The conditions that may mimic acute epiploic
      appendagitis at computed tomography (CT) include acute omental infarction,
      mesenteric panniculitis, fat-containing tumor, and primary and secondary acute
      inflammatory processes in the large bowel (eg, diverticulitis and appendicitis).
      Whereas the location of acute epiploic appendagitis is most commonly adjacent to
      the sigmoid colon, acute omental infarction is typically located in the right
      lower quadrant and often is mistaken for acute appendicitis. It is important to
      correctly diagnose acute epiploic appendagitis and acute omental infarction on CT
      images because these conditions may be mistaken for acute abdomen, and the
      mistake may lead to unnecessary surgery. The CT features of acute epiploic
      appendagitis include an oval lesion 1.5-3.5 cm in diameter, with attenuation
      similar to that of fat and with surrounding inflammatory changes, that abuts the
      anterior sigmoid colon wall. The CT features of acute omental infarction include
      a well-circumscribed triangular or oval heterogeneous fatty mass with a whorled
      pattern of concentric linear fat stranding between the anterior abdominal wall
      and the transverse or ascending colon. As CT increasingly is used for the
      evaluation of acute abdomen, radiologists are likely to see acute epiploic
      appendagitis and its mimics more often. Recognition of these conditions on CT
      images will allow appropriate management of acute abdominal pain and may help to
      prevent unnecessary surgery.

PMID- 16284133
TI  - Cardiac MR imaging and MR angiography for assessment of complex tetralogy of
      Fallot and pulmonary atresia.
AB  - Breath-hold electrocardiographically gated cardiac magnetic resonance (MR)
      imaging and contrast material-enhanced MR angiography are emerging as ideal
      techniques for the evaluation of complex congenital heart disease. Tetralogy of
      Fallot is the most common cause of cyanotic congenital heart disease and, in its
      classic form, is associated with varying degrees of hypoplasia of the central and
      peripheral pulmonary arteries, with valvar pulmonary atresia and collateral
      aortopulmonary vessels occupying the extreme end of the spectrum. Accurate
      assessment of the size and anatomy of the pulmonary arteries is often difficult
      with echocardiography and conventional cineangiography. Compared with
      echocardiography in particular, cardiac MR imaging with three-dimensional
      reconstruction has distinct advantages for pre- or postoperative assessment of
      pulmonary anatomy in patients with tetralogy of Fallot and pulmonary atresia. MR
      imaging enables the clear and complete depiction of anatomy and thus can provide
      additional information about pulmonary artery abnormalities that are difficult to
      evaluate with conventional cardiac imaging techniques.

PMID- 16284134
TI  - Fibrous lesions of the breast: imaging-pathologic correlation.
AB  - Fibroepithelial lesions of the breast are commonly seen in clinical practice. The
      masses are composed of a combination of prominent stroma and varying glandular
      elements. Fibroadenomas, benign lesions that derive from the terminal duct
      lobular unit, are the most common and are often identified at clinical
      examination or mammography as circumscribed masses. Benign mesenchymal tumors
      include focal fibrosis, pseudoangiomatous stromal hyperplasia, and fibromatosis
      or desmoid tumor. Phyllodes tumor, which is similar to fibroadenoma but has
      increased cellularity in the stroma, is typically benign but has malignant
      potential. Diabetic fibrous mastopathy, a stromal proliferation found in patients
      with juvenile-onset insulin-dependent diabetes, is a reactive fibrous lesion.
      Most of these lesions manifest as masses at clinical and/or mammographic
      examination. Some (eg, fibroadenomas) may be associated with calcifications.
      Except for fibromatosis and phyllodes tumor, fibroepithelial lesions need not be
      excised if the diagnosis is confirmed by the results of histologic analysis at
      percutaneous biopsy. To correctly differentiate between fibrous breast lesions
      that are benign and those that should be resected, the physician must be familiar
      with the correlated radiologic-pathologic findings in the various lesion types.

PMID- 16284135
TI  - Sonographic examination of the carotid arteries.
AB  - Ultrasonography (US) of the carotid arteries is a common imaging study performed
      for diagnosis of carotid artery disease. In the United States, carotid US may be
      the only diagnostic imaging modality performed before carotid endarterectomy.
      Therefore, the information obtained with carotid US must be reliable and
      reproducible. Technical parameters that can affect the accuracy of carotid US
      results include the Doppler angle, sample volume box, color Doppler sampling
      window, color velocity scale, and color gain. Important factors in diagnosis of
      atherosclerotic disease of the extracranial carotid arteries are the intima-media
      thickness, plaque morphology, criteria for grading stenosis, limiting factors
      such as the presence of dissection or cardiac abnormalities, distinction between
      near occlusion and total occlusion, and the presence of a subclavian steal.
      Challenges to the consistency of carotid US results may include lack of a
      standard protocol, poor Doppler technique, inexperience in interpretation of
      hemodynamic changes reflected in the Doppler waveform, artifacts, and physical
      challenges. Hindrances in the classification of problematic carotid artery
      stenoses may be overcome by following a standard protocol and optimizing scanning
      techniques and Doppler settings.

PMID- 16284136
TI  - Normal sonographic anatomy of the wrist and hand.
AB  - The advent of ultra-high-frequency sonographic transducers has significantly
      enhanced our ability to image superficial structures. As a result, sonography now
      can be used to assess injuries of the tendons in the wrist and hand. A clear
      understanding of normal sonographic anatomy is required to prevent misdiagnosis
      and ensure optimal patient care. The anatomy of the wrist and hand is best
      described by considering the extensor and flexor surfaces separately. The carpal
      extensor retinaculum divides the dorsal extensor tendons into six separate
      synovial compartments, which are demarcated by the points of its attachment to
      the radius and ulna. The course of these tendons from the wrist to the sites of
      their insertion can be traced by using sonography. The intrinsic wrist ligaments,
      triangular fibrocartilage, and dorsal finger extensor hood also can be assessed
      sonographically. The anatomy of the flexor surface of the wrist is defined
      principally by the flexor retinaculum. The median nerve, which is located deep to
      the retinaculum in the carpal tunnel, and the ulnar nerve, which is superficial
      to the retinaculum in the Guyon canal, can be easily detected. The long flexor
      tendons in the wrist and hand are also clearly depicted at sonography. The flexor
      annular pulley system is formed by five foci of thickening along the long flexor
      finger tendon synovial sheath, and the second and fourth annular pulleys can be
      identified sonographically in most patients. Sonography provides a rapid, cheap,
      noninvasive, and dynamic method for examination of the soft-tissue structures of
      the wrist and hand. Familiarity with the appearance of normal anatomic structures
      is a prerequisite for reliable interpretation of the resultant sonograms.

PMID- 16284137
TI  - Rotator cuff tears: clinical, radiographic, and US findings.
AB  - Rotator cuff tears are a common cause of shoulder pain. Clinical and radiographic
      findings can suggest the presence of a rotator cuff tear. The most sensitive
      clinical findings are impingement and the "arc of pain" sign. Radiographic
      findings are usually normal in the acute setting, although the "active abduction"
      view may show decreased acromiohumeral distance. In more chronic cases, an outlet
      view may show decreased opacity and decreased size of the supraspinatus muscle
      due to atrophy. In late cases, the humeral head may become subluxated superiorly,
      and secondary degenerative arthritis of the glenohumeral joint may ensue.
      Ultrasonography (US), with over 90% sensitivity and specificity, can help confirm
      the diagnosis in clinically or radiographically equivocal cases. US can also
      reveal the presence of other abnormalities that may mimic rotator cuff tear at
      clinical examination, including tendinosis, calcific tendinitis, subacromial
      subdeltoid bursitis, greater tuberosity fracture, and adhesive capsulitis.

PMID- 16284139
TI  - Imaging of penile neoplasms.
AB  - The assessment of penile cancer on the basis of clinical findings alone can often
      result in inaccurate staging and suboptimal treatment. Imaging of primary penile
      cancer and metastatic lymphadenopathy can help optimize planning of both primary
      tumor resection and treatment for lymph node metastases. Magnetic resonance (MR)
      imaging is the most accurate imaging modality in the assessment of primary penile
      cancers, which usually manifest as solitary, ill-defined infiltrating tumors that
      are hypointense on both T1- and T2-weighted MR images. T2-weighted MR imaging
      allows delineation of the tumor margin and of any extension into the penile
      shaft. On gadolinium-enhanced T1-weighted images, the tumors enhance to a greater
      extent than do the corpora cavernosa. In addition, the recently introduced
      technique known as lymphotrophic nanoparticle-enhanced MR imaging can help
      identify metastatic lymph node disease. However, further studies will be needed
      to determine the role of this imaging technique in clinical practice. Computed
      tomography does not clearly depict the local extension of primary penile cancer;
      however, it is useful in assessing metastases and postoperative complications.

PMID- 16284138
TI  - Transitional cell carcinoma of the upper urinary tract: spectrum of imaging
      findings.
AB  - Transitional cell carcinoma (TCC) accounts for up to 10% of neoplasms of the
      upper urinary tract and usually manifests as hematuria. Imaging plays an
      important role in assessment of upper tract disease, unlike in bladder TCC,
      diagnosis of which is usually made at cystoscopy. Traditional imaging modalities,
      such as excretory urography, retrograde pyelography, and ultrasonography, still
      play pivotal roles in diagnosis of upper tract TCC, in combination with
      endourologic techniques. The multicentric nature of TCC makes assessment of the
      entire urothelium essential before treatment. The advent of minimally invasive
      surgery, which allows renal preservation in selected patients, makes accurate
      tumor staging mandatory to determine the appropriate therapy; staging is usually
      performed with computed tomography (CT) or magnetic resonance (MR) imaging.
      Vigilant urologic and radiologic follow-up is warranted to assess for
      metachronous lesions and recurrence. The emerging technique of CT urography
      allows detection of urinary tract tumors and calculi, assessment of perirenal
      tissues, and staging of lesions; it may offer the opportunity for one-stop
      evaluation in the initial assessment of hematuria and in follow-up of TCC.
      Similar MR imaging protocols can be used in patients who are not candidates for
      CT urography, although detection of urinary tract calcifications may be
      suboptimal.

PMID- 16284140
TI  - Multi-detector row CT and postprocessing techniques in the assessment of diffuse
      lung disease.
AB  - Many acute and chronic lung diseases are characterized by diffuse infiltration of
      the lung parenchyma. High-resolution computed tomography (CT) has been widely
      accepted as the imaging standard of reference for the assessment of these
      diseases. However, only approximately 10% of the lung parenchyma is scanned with
      high-resolution CT, and characteristic foci of disease may be missed. With use of
      the established characteristic high-resolution CT patterns, multi-detector row
      chest CT has revolutionized the evaluation of diffuse lung disease. Multi
      detector row CT generates isotropic volumetric high-resolution data, allowing
      contiguous three-dimensional (3D) visualization of the lung parenchyma, with the
      capacity to create high-quality two-dimensional (2D) and 3D reformatted images.
      Minimum intensity projection is the postprocessing technique of choice for the
      detection and characterization of most patterns of diffuse lung disease. Maximum
      intensity projection (MIP) allows the detection and characterization of
      micronodules; the recognition of enlarged pulmonary veins, which is extremely
      useful in the diagnosis of pulmonary edema and the assessment of mosaic
      perfusion; and differentiation between perilymphatic, miliary, and centrilobular
      distribution. MIP can also help differentiate between constrictive bronchiolitis
      and mixed emphysema. Two-dimensional reformatted images are now of equal
      importance with the 2D axial images in diagnosing specific diffuse lung diseases.
      In the future, 3D reformatted images may be used to help quantify these
      disorders.

PMID- 16284142
TI  - From the archives of the AFIP: Oligodendroglioma and its variants: radiologic
      pathologic correlation.
AB  - Oligodendroglioma is the third most common glial neoplasm and most commonly
      arises in the frontal lobe. It occurs in males more frequently, and the peak
      manifestation is during the 5th and 6th decades. Children are affected much less
      commonly. The clinical presentation is often of several years duration with most
      patients presenting with seizures, reflecting the strong predilection of this
      tumor to involve the cortical gray matter. Current histopathologic classification
      schemes recognize two main types of tumors: well-differentiated oligodendroglioma
      and its anaplastic variant. Less commonly, neoplastic mixtures of both
      oligodendroglial and astrocytic components occur and are termed
      oligoastrocytomas, with both well-differentiated and anaplastic forms. Surgical
      resection is the mainstay of initial treatment, and many patients experience a
      long progression-free period. Recent genotyping has revealed chromosomal loss of
      1p and 19q as a genetic signature in most oligodendrogliomas, and these tumors
      respond favorably to chemotherapy. Hence, radiation therapy is now generally
      reserved for partially resected tumors and cases that failed to benefit from
      chemotherapy. At cross-sectional imaging, the tumor characteristically involves
      the cortical gray matter and frequently contains calcification. Robust
      enhancement is not a common feature and suggests transformation to a higher
      histologic grade. Advanced magnetic resonance imaging techniques and metabolic
      imaging play increasingly important roles in both pre- and postoperative
      assessment of these complex neoplasms.

PMID- 16284141
TI  - Pulmonary artery interventions: an overview.
AB  - Interventional radiologists should be familiar with minimally invasive procedures
      used to treat various abnormalities of the pulmonary arteries. These well
      established techniques, which obviate open surgery, are safe and effective when
      performed by an experienced interventionalist. Catheter-based thrombolysis with
      intrapulmonary arterial infusion of thrombolytic drugs, percutaneous
      thrombectomy, or embolus fragmentation can be performed in patients with life
      threatening pulmonary embolism. Pulmonary artery stenoses, mainly encountered in
      patients with pulmonary vasculitis (as in Behcet disease or Takayasu arteritis),
      may be treated with balloon angioplasty and stent placement. Transcatheter
      embolization of pulmonary arteriovenous malformation is the standard treatment
      for hereditary hemorrhagic telangiectasia and is a very effective alternative to
      surgery to correct an aneurysm or pseudoaneurysm. In cases of hemoptysis that
      originates in the pulmonary artery, early diagnosis is mandatory for treatment
      with embolization. Percutaneous retrieval of foreign bodies from the heart or the
      pulmonary arteries and endovascular biopsy should also be part of the
      armamentarium of interventional radiologists.

PMID- 16284143
TI  - Best cases from the AFIP: Borderline papillary serous tumor of the right ovary.

PMID- 16284144
TI  - Visceral manifestations of Klippel-Trenaunay syndrome.

PMID- 16284145
TI  - Informatics in radiology (infoRAD): multimedia extension of medical imaging
      resource center teaching files.
AB  - A new method has been developed for multimedia enhancement of electronic teaching
      files created by using the standard protocols and formats offered by the Medical
      Imaging Resource Center (MIRC) project of the Radiological Society of North
      America. The typical MIRC electronic teaching file consists of static pages only;
      with the new method, audio and visual content may be added to the MIRC electronic
      teaching file so that the entire image interpretation process can be recorded for
      teaching purposes. With an efficient system for encoding the audiovisual record
      of on-screen manipulation of radiologic images, the multimedia teaching files
      generated are small enough to be transmitted via the Internet with acceptable
      resolution. Students may respond with the addition of new audio and visual
      content and thereby participate in a discussion about a particular case. MIRC
      electronic teaching files with multimedia enhancement have the potential to
      augment the effectiveness of diagnostic radiology teaching.

PMID- 16284147
TI  - Biodiversity science evolves.

PMID- 16284146
TI  - Informatics in radiology (infoRAD): an open source framework for modification and
      communication of DICOM objects.
AB  - A configurable framework has been developed that can receive, modify, and export
      images in different picture archiving and communication system scenarios. The
      framework has three main components: a receiver for Digital Imaging and
      Communications in Medicine (DICOM) objects, a processing pipeline to apply one or
      more modifications to these objects, and one or more senders to send the
      processed objects to predefined addresses. The toolbox programming was
      implemented as an open source project in Java. The processing pipeline uses the
      concept of configurable plug-ins. One plug-in is user programmable by means of
      extensible stylesheet language files and allows conversion of DICOM objects to
      extensible markup language documents or other file types. Input and output
      channels are the DICOM Storage service, DICOM compact disks-read-only memory (CD
      ROMs), and the local file system. The toolbox has been successfully applied to
      different clinical scenarios, including the correction of DICOM objects from non
      Integrating the Healthcare Enterprise (IHE) conform modalities, pseudonaming of
      DICOM images, and use of the IHE Portable Data for Imaging profile with import
      and export of CD-ROMs. The toolbox has proved reliability in the clinical
      routine. Because of the open programming interfaces, the functionality can easily
      be adapted to future applications.

PMID- 16284149
TI  - Hurricane Katrina. Levees came up short, researchers tell Congress.

PMID- 16284148
TI  - Public health. Pandemic or not, experts welcome Bush flu plan.

PMID- 16284150
TI  - ITER. Fusion leaders make a diplomatic choice.

PMID- 16284151
TI  - Astrophysics. Surprise neutron star suggests black holes are hard to make.

PMID- 16284152
TI  - National Science Foundation. Board suggests how to thrive under stress.

PMID- 16284153
TI  - U.S. higher education. Schools cheer rise in foreign students.

PMID- 16284155
TI  - Biogeography. Is everything everywhere?

PMID- 16284154
TI  - Epidemiology. Russian cancer study adds to the indictment of low-dose radiation.

PMID- 16284156
TI  - Profile: Susan Greenfield. The baroness and the brain.

PMID- 16284158
TI  - Drug research. Trying to catch troublemakers with a metabolic profile.

PMID- 16284157
TI  - Evolution. Ancient DNA yields clues to the puzzle of European origins.

PMID- 16284159
TI  - Paleontology. Tyrannosaurus rex gets sensitive.

PMID- 16284160
TI  - Balancing risk and recovery.

PMID- 16284161
TI  - Suggesting reviewers affects outcome?

PMID- 16284162
TI  - Correcting temperature data sets.

PMID- 16284164
TI  - Illusory statistics.

PMID- 16284163
TI  - Causation, Vioxx, and legal issues.

PMID- 16284165
TI  - Science and law. WMD sensors--search and seizure.

PMID- 16284166
TI  - Evolution. The tree-thinking challenge.

PMID- 16284167
TI  - Chemistry. Following the flow of energy in biomolecules.

PMID- 16284168
TI  - Biochemistry. The photosynthesis "oxygen clock" gets a new number.

PMID- 16284169
TI  - Planetary science. What do we need to know to land on the Moon again?

PMID- 16284170
TI  - Biomedicine. Separation of conjoined hormones yields appetite rivals.

PMID- 16284171
TI  - Pattern-oriented modeling of agent-based complex systems: lessons from ecology.
AB  - Agent-based complex systems are dynamic networks of many interacting agents;
      examples include ecosystems, financial markets, and cities. The search for
      general principles underlying the internal organization of such systems often
      uses bottom-up simulation models such as cellular automata and agent-based
      models. No general framework for designing, testing, and analyzing bottom-up
      models has yet been established, but recent advances in ecological modeling have
      come together in a general strategy we call pattern-oriented modeling. This
      strategy provides a unifying framework for decoding the internal organization of
      agent-based complex systems and may lead toward unifying algorithmic theories of
      the relation between adaptive behavior and system complexity.

PMID- 16284172
TI  - Multiple transatlantic introductions of the western corn rootworm.
AB  - The invasion of Europe by the western corn rootworm, North America's most
      destructive corn pest, is ongoing and represents a serious threat to European
      agriculture. Because this pest was initially introduced in Central Europe, it was
      believed that subsequent outbreaks in Western Europe originated from this area.
      Using model-based Bayesian analyses of the genetic variability of the western
      corn rootworm, we demonstrate that this belief is false: There have been at least
      three independent introductions from North America during the past two decades.
      This result raises questions about changing circumstances that have enabled a
      sudden burst of transatlantic introductions.

PMID- 16284173
TI  - Transient floral change and rapid global warming at the Paleocene-Eocene
      boundary.
AB  - Rapid global warming of 5 degrees to 10 degrees C during the Paleocene-Eocene
      Thermal Maximum (PETM) coincided with major turnover in vertebrate faunas, but
      previous studies have found little floral change. Plant fossils discovered in
      Wyoming, United States, show that PETM floras were a mixture of native and
      migrant lineages and that plant range shifts were large and rapid (occurring
      within 10,000 years). Floral composition and leaf shape and size suggest that
      climate warmed by approximately 5 degrees C during the PETM and that
      precipitation was low early in the event and increased later. Floral response to
      warming and/or increased atmospheric CO2 during the PETM was comparable in rate
      and magnitude to that seen in postglacial floras and to the predicted effects of
      anthropogenic carbon release and climate change on future vegetation.

PMID- 16284174
TI  - Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on
      food intake.
AB  - Ghrelin, a circulating appetite-inducing hormone, is derived from a prohormone by
      posttranslational processing. On the basis of the bioinformatic prediction that
      another peptide also derived from proghrelin exists, we isolated a hormone from
      rat stomach and named it obestatin-a contraction of obese, from the Latin
      "obedere," meaning to devour, and "statin," denoting suppression. Contrary to the
      appetite-stimulating effects of ghrelin, treatment of rats with obestatin
      suppressed food intake, inhibited jejunal contraction, and decreased body-weight
      gain. Obestatin bound to the orphan G protein-coupled receptor GPR39. Thus, two
      peptide hormones with opposing action in weight regulation are derived from the
      same ghrelin gene. After differential modification, these hormones activate
      distinct receptors.

PMID- 16284175
TI  - Direct visualization of the formation of single-molecule conjugated copolymers.
AB  - Electrochemical polymerization of two different kinds of thiophene monomers on an
      iodine-covered gold surface created highly assembled conjugated copolymers with
      different electronic structures. A scanning tunneling microscope revealed images
      of several linkage types: diblock, triblock, and multiblock. The single strand of
      conjugated copolymers exhibited an anomalous swinging motion on the surface. This
      technique presents the possibility of understanding the copolymerization process
      from the different monomers on the single-molecular scale and of building single
      molecule superlattices on a surface through controlled electropolymerization.

PMID- 16284176
TI  - Structural observation of the primary isomerization in vision with femtosecond
      stimulated Raman.
AB  - The primary event that initiates vision is the light-induced 11-cis to all-trans
      isomerization of retinal in the visual pigment rhodopsin. Despite decades of
      study with the traditional tools of chemical reaction dynamics, both the timing
      and nature of the atomic motions that lead to photoproduct production remain
      unknown. We used femtosecond-stimulated Raman spectroscopy to obtain time
      resolved vibrational spectra of the molecular structures formed along the
      reaction coordinate. The spectral evolution of the vibrational features from 200
      femtoseconds to 1 picosecond after photon absorption reveals the temporal
      sequencing of the geometric changes in the retinal backbone that activate this
      receptor.

PMID- 16284177
TI  - Ancient DNA from the first European farmers in 7500-year-old Neolithic sites.
AB  - The ancestry of modern Europeans is a subject of debate among geneticists,
      archaeologists, and anthropologists. A crucial question is the extent to which
      Europeans are descended from the first European farmers in the Neolithic Age 7500
      years ago or from Paleolithic hunter-gatherers who were present in Europe since
      40,000 years ago. Here we present an analysis of ancient DNA from early European
      farmers. We successfully extracted and sequenced intact stretches of maternally
      inherited mitochondrial DNA (mtDNA) from 24 out of 57 Neolithic skeletons from
      various locations in Germany, Austria, and Hungary. We found that 25% of the
      Neolithic farmers had one characteristic mtDNA type and that this type formerly
      was widespread among Neolithic farmers in Central Europe. Europeans today have a
      150-times lower frequency (0.2%) of this mtDNA type, revealing that these first
      Neolithic farmers did not have a strong genetic influence on modern European
      female lineages. Our finding lends weight to a proposed Paleolithic ancestry for
      modern Europeans.

PMID- 16284178
TI  - Photosynthetic O2 formation tracked by time-resolved x-ray experiments.
AB  - Plants and cyanobacteria produce atmospheric dioxygen from water, powered by
      sunlight and catalyzed by a manganese complex in photosystem II. A classic S
      cycle model for oxygen evolution involves five states, but only four have been
      identified. The missing S4 state is particularly important because it is directly
      involved in dioxygen formation. Now progress comes from an x-ray technique that
      can monitor redox and structural changes in metal centers in real time with 10
      microsecond resolution. We show that in the O2-formation step, an intermediate is
      formed--the enigmatic S4 state. Its creation is identified with a deprotonation
      process rather than the expected electron-transfer mechanism. Subsequent electron
      transfer would give an additional S4' state, thus extending the fundamental S
      state cycle of dioxygen formation.

PMID- 16284179
TI  - Small-molecule inhibition of TNF-alpha.
AB  - We have identified a small-molecule inhibitor of tumor necrosis factor alpha (TNF
      alpha) that promotes subunit disassembly of this trimeric cytokine family member.
      The compound inhibits TNF-alpha activity in biochemical and cell-based assays
      with median inhibitory concentrations of 22 and 4.6 micromolar, respectively.
      Formation of an intermediate complex between the compound and the intact trimer
      results in a 600-fold accelerated subunit dissociation rate that leads to trimer
      dissociation. A structure solved by x-ray crystallography reveals that a single
      compound molecule displaces a subunit of the trimer to form a complex with a
      dimer of TNF-alpha subunits.

PMID- 16284180
TI  - Structure of a V3-containing HIV-1 gp120 core.
AB  - The third variable region (V3) of the HIV-1 gp120 envelope glycoprotein is
      immunodominant and contains features essential for coreceptor binding. We
      determined the structure of V3 in the context of an HIV-1 gp120 core complexed to
      the CD4 receptor and to the X5 antibody at 3.5 angstrom resolution. Binding of
      gp120 to cell-surface CD4 would position V3 so that its coreceptor-binding tip
      protrudes 30 angstroms from the core toward the target cell membrane. The
      extended nature and antibody accessibility of V3 explain its immunodominance.
      Together, the results provide a structural rationale for the role of V3 in HIV
      entry and neutralization.

PMID- 16284181
TI  - The pseudo-response regulator Ppd-H1 provides adaptation to photoperiod in
      barley.
AB  - Plants commonly use photoperiod (day length) to control the timing of flowering
      during the year, and variation in photoperiod response has been selected in many
      crops to provide adaptation to different environments and farming practices.
      Positional cloning identified Ppd-H1, the major determinant of barley photoperiod
      response, as a pseudo-response regulator, a class of genes involved in circadian
      clock function. Reduced photoperiod responsiveness of the ppd-H1 mutant, which is
      highly advantageous in spring-sown varieties, is explained by altered circadian
      expression of the photoperiod pathway gene CONSTANS and reduced expression of its
      downstream target, FT, a key regulator of flowering.

PMID- 16284182
TI  - Oxidative mediated lipid peroxidation recapitulates proarrhythmic effects on
      cardiac sodium channels.
AB  - Sudden cardiac death attributable to ventricular tachycardia/fibrillation (VF)
      remains a catastrophic outcome of myocardial ischemia and infarction. At the same
      time, conventional antagonist drugs targeting ion channels have yielded poor
      survival benefits. Although pharmacological and genetic models suggest an
      association between sodium (Na+) channel loss-of-function and sudden cardiac
      death, molecular mechanisms have not been identified that convincingly link
      ischemia to Na+ channel dysfunction and ventricular arrhythmias. Because ischemia
      can evoke the generation of reactive oxygen species, we explored the effect of
      oxidative stress on Na+ channel function. We show here that oxidative stress
      reduces Na+ channel availability. Both the general oxidant tert-butyl
      hydroperoxide and a specific, highly reactive product of the isoprostane pathway
      of lipid peroxidation, E2-isoketal, potentiate inactivation of cardiac Na+
      channels in human embryonic kidney (HEK)-293 cells and cultured atrial (HL-1)
      myocytes. Furthermore, E2-isoketals were generated in the epicardial border zone
      of the canine healing infarct, an arrhythmogenic focus where Na+ channels exhibit
      similar inactivation defects. In addition, we show synergistic functional effects
      of flecainide, a proarrhythmic Na+ channel blocker, and oxidative stress. These
      data suggest Na+ channel dysfunction evoked by lipid peroxidation is a candidate
      mechanism for ischemia-related conduction abnormalities and arrhythmias.

PMID- 16284183
TI  - PTEN activity is modulated during ischemia and reperfusion: involvement in the
      induction and decay of preconditioning.
AB  - Ischemic preconditioning (IPC), a brief period of ischemia and reperfusion (I/R),
      generates profound but transient protection against a subsequent prolonged
      ischemic episode. The serine-threonine kinase Akt has been shown to mediate IPC,
      and Akt activation is negatively regulated by the phosphatase PTEN, but whether
      PTEN activity is modulated by IPC has not been investigated. When isolated,
      perfused rat hearts were subjected to an IPC stimulus consisting of 15-minute
      ischemia and 30-minute reperfusion (I-15/R-30), PTEN protein levels and activity
      were decreased, and levels of phospho-AKT were increased, relative to nonischemic
      hearts. Hearts subjected to IPC demonstrated improved recovery of cardiac
      function when subsequently subjected to I-30/R-45 as compared with hearts
      subjected to I-30/R-45 without prior IPC. When hearts were subjected to I-15
      followed by R-30, R-60, or R-120, PTEN reaccumulated gradually and its activity
      was restored. Phospho-Akt levels at R-120 were decreased and these hearts were no
      longer protected against injury when subjected to I-30/R-45. Wortmannin
      administration during reperfusion blocked Akt activation and PTEN reaccumulation.
      In ischemic hearts, PTEN was rapidly degraded. Pretreatment with proteasome
      inhibitor MG132 blocked ischemia-induced degradation of PTEN and blocked IPC.
      Reperfusion following I-15 induced oxidation of the remaining PTEN, leading to
      Akt activation. Perfusion of H2(O2) was sufficient to induce Akt activation.
      Thus, loss of PTEN activity leads to induction of IPC and feedback mechanisms
      designed to ensure that Akt activation is transient are responsible for decay of
      IPC.

PMID- 16284184
TI  - Gab1, SHP2, and protein kinase A are crucial for the activation of the
      endothelial NO synthase by fluid shear stress.
AB  - Fluid shear stress enhances NO production in endothelial cells by a mechanism
      involving the activation of the phosphatidylinositol 3-kinase and the
      phosphorylation of the endothelial NO synthase (eNOS). We investigated the role
      of the scaffolding protein Gab1 and the tyrosine phosphatase SHP2 in this signal
      transduction cascade in cultured and native endothelial cells. Fluid shear stress
      elicited the phosphorylation and activation of Akt and eNOS as well as the
      tyrosine phosphorylation of Gab1 and its association with the p85 subunit of
      phosphatidylinositol 3-kinase and SHP2. Overexpression of a Gab1 mutant lacking
      the pleckstrin homology domain abrogated the shear stress-induced phosphorylation
      of Akt but failed to affect the phosphorylation or activity of eNOS. The latter
      response, however, was sensitive to a protein kinase A (PKA) inhibitor. Mutation
      of Gab1 Tyr627 to phenylalanine (YF-Gab1) to prevent the binding of SHP2
      completely prevented the shear stress-induced phosphorylation of eNOS, leaving
      the Akt response intact. A dominant-negative SHP2 mutant prevented the activation
      of PKA and phosphorylation of eNOS without affecting that of Akt. Moreover, shear
      stress elicited the formation of a signalosome complex including eNOS, Gab1, SHP2
      and the catalytic subunit of PKA. In isolated murine carotid arteries, flow
      induced vasodilatation was prevented by a PKA inhibitor as well as by
      overexpression of either the YF-Gab1 or the dominant-negative SHP2 mutant. Thus,
      the shear stress-induced activation of eNOS depends on Gab1 and SHP2, which, in
      turn, regulate the phosphorylation and activity of eNOS by a PKA-dependent but
      Akt-independent mechanism.

PMID- 16284185
TI  - Tissue-resident bone marrow-derived progenitor cells: key players in hypoxia
      induced angiogenesis.

PMID- 16284186
TI  - Genetic strategies to elucidate the roles of matrix metalloproteinases in
      atherosclerotic plaque growth and stability.

PMID- 16284187
TI  - New function of calreticulin: calreticulin-dependent mRNA destabilization.

PMID- 16284188
TI  - Cardiac remodeling: UPS lost in transit.

PMID- 16284189
TI  - Redox-dependent transcriptional regulation.
AB  - Reactive oxygen species contribute to the pathogenesis of a number of disparate
      disorders including tissue inflammation, heart failure, hypertension, and
      atherosclerosis. In response to oxidative stress, cells activate expression of a
      number of genes, including those required for the detoxification of reactive
      molecules as well as for the repair and maintenance of cellular homeostasis. In
      many cases, these induced genes are regulated by transcription factors whose
      structure, subcellular localization, or affinity for DNA is directly or
      indirectly regulated by the level of oxidative stress. This review summarizes the
      recent progress on how cellular redox status can regulate transcription-factor
      activity and the implications of this regulation for cardiovascular disease.

PMID- 16284190
TI  - Bile acids decrease hepatic paraoxonase 1 expression and plasma high-density
      lipoprotein levels via FXR-mediated signaling of FGFR4.
AB  - OBJECTIVE: The purpose of this research was to determine how dietary bile acids
      repress hepatic expression of paraoxonase 1 (PON1). METHODS AND RESULTS: C57BL/6
      mice and C3H/HeJ mice, having different susceptibilities to atherosclerosis, were
      fed a chow diet and an atherogenic diet containing taurocholate. Compared with
      the more atherosclerosis-susceptible C57BL/6 mice, C3H/HeJ mice display
      resistance to dietary bile acid repression of hepatic PON1 mRNA and decreased
      high-density lipoprotein cholesterol. Whereas knockout of toll receptor 4 did not
      affect response to taurocholate, deletion of either FXR or FGFR4 blocked
      taurocholate repression of PON1 and CYP7A1. FGF19, an activator of FGFR4
      expressed in human ileum, decreased expression of both PON1 and CYP7A1 expression
      by human hepatoma cells. In all of the mice studied, dietary taurocholate
      increased ileal expression of FGF15, a FXR-inducible murine homologue of human
      FGF19. CONCLUSIONS: Hepatic PON1 and CYP7A1 mRNA expression is repressed by bile
      acids via FXR-mediated induction of FGF15. Thus, the inability of C3H/HeJ mice to
      display taurocholate repression of PON1 and CYP7A1 mRNAs was not because of a
      lack of induction of FGF15 but rather signaling events distal to FGF15-FGFR4
      association.

PMID- 16284191
TI  - Identification of macrophage arginase I as a new candidate gene of
      atherosclerosis resistance.
AB  - OBJECTIVE: Our laboratory has previously created 2 strains of rabbits with
      genetically determined high-atherosclerotic response (HAR) and low
      atherosclerotic response (LAR). The aim of the present study was to identify new
      genes of atherosclerosis susceptibility in macrophages from the 2 strains.
      METHODS AND RESULTS: Suppression subtractive hybridization was used to screen for
      genes with higher expression in macrophages from LAR rabbits. We identified a
      cDNA fragment with high homology to human arginase I (AI; 91%) and subsequently
      cloned the full-length cDNA of the rabbit homologue. Quantitative RT-PCR revealed
      a significantly higher macrophage AI mRNA expression in LAR rabbits than in HAR
      rabbits (77428+/-10941 versus 34344+/-4538; P=0.002; copies/10(6) copies beta
      actin), which also correlated with a significantly higher arginase enzyme
      activity. Northern blot analysis led to the identification of a size polymorphism
      of AI mRNA. This was because of a 413 bp C-repeat insertion in the 3'
      untranslated region. The shorter transcript variant was predominantly expressed
      in LAR rabbits and associated with significantly higher AI mRNA expression
      levels. Transfection experiments indicated decreased mRNA stability of the long
      AI variant. CONCLUSIONS: High expression of arginase I in macrophages may
      contribute to atherosclerosis resistance of LAR rabbits, possibly by conferring
      antiinflammatory effects in the vessel wall.

PMID- 16284192
TI  - Effects of pioglitazone on lipoproteins, inflammatory markers, and adipokines in
      nondiabetic patients with metabolic syndrome.
AB  - OBJECTIVE: The purpose of this research was to evaluate the short-term effects of
      pioglitazone (PIO) on high-density lipoprotein cholesterol (HDL-C) and other
      metabolic parameters in nondiabetic patients with metabolic syndrome (MetSyn).
      METHODS AND RESULTS: Sixty nondiabetic adults with low HDL-C and MetSyn were
      randomized to PIO or matching placebo for 12 weeks. PIO increased HDL-C by 15%
      and 14% at 6 and 12 weeks, respectively, compared with placebo (P<0.001). Changes
      in HDL-C were correlated to changes in adiponectin (r=0.34; P=0.01) but not to
      changes in insulin resistance. PIO did not affect serum triglycerides or low
      density lipoprotein (LDL) cholesterol concentrations but reduced the number of
      small LDL particles by 18% (P<0.001). PIO reduced median C-reactive protein
      levels by 31% (P<0.001) and mean resistin levels by 10% (P=0.02) while increasing
      mean serum levels of adiponectin by 111% (P<0.001) compared with placebo. PIO did
      not affect weight and modestly decreased insulin resistance. CONCLUSIONS: In
      nondiabetic patients with low HDL-C and MetSyn, PIO significantly raised HDL-C
      and favorably affected lipoprotein particle size, markers of inflammation, and
      adipokines without changes in triglycerides, LDL-C, or weight. These results
      suggest that PIO has direct effects on HDL, which may contribute to its
      antiatherogenic effects.

PMID- 16284193
TI  - Assembly of high-density lipoprotein.
AB  - Mammalian somatic cells do not catabolize cholesterol and need to export it for
      its homeostasis at the levels of cells and whole bodies. This reaction may reduce
      intracellularly accumulated cholesterol in excess and would contribute to
      prevention or regression of the initial stage of atherosclerosis. High-density
      lipoprotein (HDL) is thought to play a main role in this reaction, and 2
      independent mechanisms are proposed for this reaction. First, cholesterol is
      exchanged in a nonspecific physicochemical manner between cell surface and
      extracellular lipoproteins, and cholesterol esterification on HDL provides a
      driving force for net removal of cell cholesterol. Second, apolipoproteins
      directly interact with cells and generate HDL by removing cellular phospholipid
      and cholesterol. This reaction is a major source of plasma HDL and is mediated by
      a membrane protein, ABCA1. Lipid-free or lipid-poor helical apolipoproteins
      primarily recruit cellular phospholipid to assemble HDL particles, and
      cholesterol enrichment in these particles is regulated independently. ABCA1 is a
      rate-limiting factor of the HDL assembly and is regulated by transcriptional
      factors and posttranscriptional factors. Posttranscriptional regulation of ABCA1
      includes modulation of its calpain-mediated degradation.

PMID- 16284194
TI  - Limitations and potentials of current motif discovery algorithms.
AB  - Computational methods for de novo identification of gene regulation elements,
      such as transcription factor binding sites, have proved to be useful for
      deciphering genetic regulatory networks. However, despite the availability of a
      large number of algorithms, their strengths and weaknesses are not sufficiently
      understood. Here, we designed a comprehensive set of performance measures and
      benchmarked five modern sequence-based motif discovery algorithms using large
      datasets generated from Escherichia coli RegulonDB. Factors that affect the
      prediction accuracy, scalability and reliability are characterized. It is
      revealed that the nucleotide and the binding site level accuracy are very low,
      while the motif level accuracy is relatively high, which indicates that the
      algorithms can usually capture at least one correct motif in an input sequence.
      To exploit diverse predictions from multiple runs of one or more algorithms, a
      consensus ensemble algorithm has been developed, which achieved 6-45% improvement
      over the base algorithms by increasing both the sensitivity and specificity. Our
      study illustrates limitations and potentials of existing sequence-based motif
      discovery algorithms. Taking advantage of the revealed potentials, several
      promising directions for further improvements are discussed. Since the sequence
      based algorithms are the baseline of most of the modern motif discovery
      algorithms, this paper suggests substantial improvements would be possible for
      them.

PMID- 16284195
TI  - Coordinate control of cell cycle regulatory genes in zebrafish development tested
      by cyclin D1 knockdown with morpholino phosphorodiamidates and hydroxyprolyl
      phosphono peptide nucleic acids.
AB  - During early zebrafish (Danio rerio) development zygotic transcription does not
      begin until the mid-blastula transition (MBT) 3 h after fertilization. MBT
      demarcates transition from synchronous short cell cycles of S and M phases
      exclusively to full cycles encompassing G1 and G2 phases. Transcriptional
      profiling and RT-PCR analyses during these phases enabled us to determine that
      this shift corresponds to decreased transcript levels of S/M phase cell cycle
      control genes (e.g. ccna2, ccnb1, ccnb2 and ccne) and increased transcript levels
      of ccnd1, encoding cyclin D1, and orthologs of p21 (p21-like) and retinoblastoma
      (Rb-like 1). To investigate the regulation of this process further, the
      translation of ccnd1 mRNA, a G1/S checkpoint control element, was impaired by
      microinjection of ccnd1-specific morpholino phosphorodiamidate (MO) 20mer or
      hydroxyprolyl-phosphono peptide nucleic acid (HypNA-pPNA) 16mer antisense
      oligonucleotides. The resulting downregulation of cyclin D1 protein resulted in
      microophthalmia and microcephaly, but not lethality. The phenotypes were not seen
      with 3-mismatch MO 20mers or 1-mismatch HypNA-pPNA 16mers, and were rescued by an
      exogenous ccnd1 mRNA construct with five mismatches. Collectively, these results
      indicate that transcription of key molecular determinants of asynchronous cell
      cycle control in zebrafish embryos commences at MBT and that the reduction of
      cyclin D1 expression compromises zebrafish eye and head development.

PMID- 16284196
TI  - Efficient isothermal expansion of human telomeric and minisatellite repeats by
      Thermococcus litoralis DNA polymerase.
AB  - Repeating DNA sequences, such as telomeres, centromeres, and micro- and mini
      satellites, comprise 50% of the genome and play important roles in regulatory and
      pathogenic mechanisms. In order to study structures and functions of such
      repeating sequences, it is important to have simple and efficient methods for
      making them in vitro. Here, we describe the efficient and convenient expansion of
      repetitive telomeric and minisatellite DNA sequences starting from small
      synthetic templates to final product lengths of several hundreds to thousands of
      nucleotides by the thermostable DNA polymerase from Thermococcus litoralis (Vent
      DNA polymerase). This enzyme was so far unknown to catalyze repeat expansion.
      Either single-stranded or double-stranded DNAs could be produced, depending on
      nucleotides present. Compared to earlier results obtained with other enzymes, the
      expansion reaction is highly efficient both in its yield and product length, and
      proceeds without thermal cycling. Moreover, the products are characterized by a
      narrow length distribution.

PMID- 16284197
TI  - A thermodynamic approach to designing structure-free combinatorial DNA word sets.
AB  - An algorithm is presented for the generation of sets of non-interacting DNA
      sequences, employing existing thermodynamic models for the prediction of duplex
      stabilities and secondary structures. A DNA 'word' structure is employed in which
      individual DNA 'words' of a given length (e.g. 12mer and 16mer) may be
      concatenated into longer sequences (e.g. four tandem words and six tandem words).
      This approach, where multiple word variants are used at each tandem word
      position, allows very large sets of non-interacting DNA strands to be assembled
      from combinations of the individual words. Word sets were generated and their
      figures of merit are compared to sets as described previously in the literature
      (e.g. 4, 8, 12, 15 and 16mer). The predicted hybridization behavior was
      experimentally verified on selected members of the sets using standard UV
      hyperchromism measurements of duplex melting temperatures (T(m)s). Additional
      experimental validation was obtained by using the sequences in formulating and
      solving a small example of a DNA computing problem.

PMID- 16284198
TI  - Quenched autoligation probes allow discrimination of live bacterial species by
      single nucleotide differences in rRNA.
AB  - Quenched autoligation (QUAL) probes are a class of self-reacting nucleic acid
      probes that give strong fluorescence signal in the presence of fully
      complementary RNAs and selectivity against single nucleotide differences in
      solution. Here, we describe experiments designed to test whether QUAL probes can
      discriminate between bacterial species by the detection of small differences in
      their 16S rRNA sequences. Probes were introduced into live cells using small
      amounts of detergent, thus eliminating the need for fixation, and fluorescence
      signal was monitored both by microscopy and by flow cytometry without any washing
      steps. The effects of probe length, modified backbone, probe concentration and
      growth state of the bacteria were investigated. The data demonstrate specific
      fluorescence discrimination between three closely related bacteria, Escherichia
      coli, Salmonella enterica and Pseudomonas putida, based on single nucleotide
      differences in their 16S rRNA. Discrimination was possible with cells in mid-log
      phase or in lag phase. These results suggest that QUAL probes may be useful for
      rapid identification of microorganisms in laboratory and clinical settings.

PMID- 16284199
TI  - Towards systematic identification of Plasmodium essential genes by transposon
      shuttle mutagenesis.
AB  - After the deciphering of the genome sequences of several Plasmodium species,
      efforts must turn to elucidating gene function and identifying essential gene
      products. However, random approaches are lacking and gene targeting is
      inefficient in Plasmodium. Here, we established shuttle transposon mutagenesis in
      Plasmodium berghei. We constructed a mini-Tn5 derivative that can transpose into
      parasite genes cloned in Escherichia coli, providing an efficient means of
      generating knockout fragments. A 10(4)-fold increase in frequencies of double
      crossover homologous recombination in the parasite using a new electroporation
      technology permits to reproducibly generate pools of distinct mutants after
      transfection with mini-Tn5-interrupted sequences. The procedure opens the way to
      the systematic identification of essential genes in Plasmodium.

PMID- 16284200
TI  - Evolving gene/transcript definitions significantly alter the interpretation of
      GeneChip data.
AB  - Genome-wide expression profiling is a powerful tool for implicating novel gene
      ensembles in cellular mechanisms of health and disease. The most popular platform
      for genome-wide expression profiling is the Affymetrix GeneChip. However, its
      selection of probes relied on earlier genome and transcriptome annotation which
      is significantly different from current knowledge. The resultant informatics
      problems have a profound impact on analysis and interpretation the data. Here, we
      address these critical issues and offer a solution. We identified several classes
      of problems at the individual probe level in the existing annotation, under the
      assumption that current genome and transcriptome databases are more accurate than
      those used for GeneChip design. We then reorganized probes on more than a dozen
      popular GeneChips into gene-, transcript- and exon-specific probe sets in light
      of up-to-date genome, cDNA/EST clustering and single nucleotide polymorphism
      information. Comparing analysis results between the original and the redefined
      probe sets reveals approximately 30-50% discrepancy in the genes previously
      identified as differentially expressed, regardless of analysis method. Our
      results demonstrate that the original Affymetrix probe set definitions are
      inaccurate, and many conclusions derived from past GeneChip analyses may be
      significantly flawed. It will be beneficial to re-analyze existing GeneChip data
      with updated probe set definitions.

PMID- 16284201
TI  - Role of the Bombyx mori R2 element N-terminal domain in the target-primed reverse
      transcription (TPRT) reaction.
AB  - R2 is a site-specific non-long terminal repeat (non-LTR) retrotransposon encoding
      a single polypeptide with reverse transcriptase, DNA endonuclease and nucleic
      acid-binding domains. The current model of R2 retrotransposition involves an
      ordered series of cleavage and polymerization steps carried out by at least two
      R2 protein subunits, one bound upstream and one bound downstream of the
      integration site. The role in the retrotransposition reaction of two conserved
      DNA-binding motifs, a C2H2 zinc finger (ZF) and a Myb motif, located within the N
      terminal domain of the protein are explored in this report. These motifs do not
      appear to play a role in RT or the ability of the protein to bind the R2 RNA
      transcript. Methylation and missing nucleoside interference-based DNA footprints
      using polypeptides to the N-terminal domain suggest the ZF and Myb motifs bind to
      regions -3 to -1 and +10 to +15 with reference to the insertion site. Mutations
      in these DNA sites or of the N-terminal protein domain blocked binding and the
      activity of the downstream subunit. Mutations of the protein domain also affected
      binding of the upstream subunit but not its function, suggesting the primary path
      to DNA target recognition by R2 involves both upstream and downstream subunits.

PMID- 16284202
TI  - Kernel-based machine learning protocol for predicting DNA-binding proteins.
AB  - DNA-binding proteins (DNA-BPs) play a pivotal role in various intra- and extra
      cellular activities ranging from DNA replication to gene expression control.
      Attempts have been made to identify DNA-BPs based on their sequence and
      structural information with moderate accuracy. Here we develop a machine learning
      protocol for the prediction of DNA-BPs where the classifier is Support Vector
      Machines (SVMs). Information used for classification is derived from
      characteristics that include surface and overall composition, overall charge and
      positive potential patches on the protein surface. In total 121 DNA-BPs and 238
      non-binding proteins are used to build and evaluate the protocol. In self
      consistency, accuracy value of 100% has been achieved. For cross-validation (CV)
      optimization over entire dataset, we report an accuracy of 90%. Using leave 1
      pair holdout evaluation, the accuracy of 86.3% has been achieved. When we
      restrict the dataset to less than 20% sequence identity amongst the proteins, the
      holdout accuracy is achieved at 85.8%. Furthermore, seven DNA-BPs with unbounded
      structures are all correctly predicted. The current performances are better than
      results published previously. The higher accuracy value achieved here originates
      from two factors: the ability of the SVM to handle features that demonstrate a
      wide range of discriminatory power and, a different definition of the positive
      patch. Since our protocol does not lean on sequence or structural homology, it
      can be used to identify or predict proteins with DNA-binding function(s)
      regardless of their homology to the known ones.

PMID- 16284203
TI  - Cost-effectiveness of cardiac resynchronization therapy: results from the CARE-HF
      trial.
AB  - AIMS: Whilst the CArdiac REsynchronization in Heart Failure (CARE-HF) trial has
      shown that cardiac resynchronization therapy (CRT) leads to reduced morbidity and
      mortality, the cost-effectiveness of this therapy remains uncertain. The aim of
      this study was to evaluate the incremental cost per quality adjusted life year
      (QALY) gained and incremental cost per life year gained of CRT plus medical
      therapy compared to medical therapy alone. METHODS AND RESULTS: This prospective
      analysis based on intention to treat data from all patients enrolled in the CARE
      HF trial at 82 clinical centres in 12 European countries. A total of 813 patients
      with New York Heart Association class III or IV heart failure due to left
      ventricular systolic dysfunction and cardiac dyssynchrony were randomized to CRT
      plus medical therapy (n = 409) vs. medical therapy alone (n = 404). During a mean
      follow-up of 29.4 months CRT was associated with increased costs (4316, 95% CI:
      1327-7485), survival (0.10 years, 95% CI: -0.01-0.21), and QALYs (0.22, 95% CI:
      0.13-0.32). The incremental cost-effectiveness ratio was 19 319 per QALY gained
      (95% CI: 5482-45 402) and 43 596 per life-year gained (95% CI: -146 236-223 849).
      These results were sensitive to the costs of the device, procedure, and
      hospitalization. CONCLUSION: Treatment with CRT appears cost-effective at the
      notional willingness to pay threshold of 29 400 (20,000 pounds sterlings) per
      QALY gained.

PMID- 16284204
TI  - Coronary heart disease: from a disease of middle-aged men in the late 1970s to a
      disease of elderly women in the 2000s.
AB  - AIMS: To analyse secular changes in the prevalence of coronary heart disease
      (CHD) and to assess changes in the burden of CHD at population level. METHODS AND
      RESULTS: Data were used from two large cross-sectional health examination surveys
      representing the entire Finnish adult population in 1980 and 2000. In the 1978-80
      survey, the sample covered 5101 individuals aged > or =45, of whom 88%
      participated. The 2000-2001 survey comprised 5310 individuals in the same age
      range. Participation rate in the health examination was 87%. Prevalence of CHD
      decreased in men and women under the age of 65 and increased among those aged >
      or =75. Prevalence of large Q-waves indicating previous myocardial infarction
      decreased in all male age groups and in women aged 65-74. The total estimated
      number of persons with CHD increased by 18% (95% CI=6-30) during the past 20
      years in Finland. In 1980, the most dominant CHD group was men aged 45-64,
      whereas in 2000, women aged > or =75 comprised the largest CHD group. CONCLUSION:
      Although the prevalence of CHD has decreased among middle-aged persons, the
      number of CHD cases has increased during the past 20 years in Finland.

PMID- 16284205
TI  - Incidence, predictors, and outcomes of coronary dissections left untreated after
      drug-eluting stent implantation.
AB  - AIMS: Coronary dissections left untreated after percutaneous coronary
      intervention are associated with unfavourable outcomes. However, their role after
      drug-eluting stent (DES) implantation is still undescribed. We assessed
      incidence, predictors, and outcomes of residual dissections in DES-treated
      lesions. METHODS AND RESULTS: Consecutive patients undergoing DES implantation
      were enrolled in four Italian centres, with baseline, procedural, and outcome
      data entered into a dedicated database. Residual dissections were classified
      according to the National Heart Lung and Blood Institute criteria. End-points of
      interest were in-hospital, 1-month, and 6-month major adverse cardiovascular
      events (MACE, i.e. death, myocardial infarction, or target vessel
      revascularization), and stent thrombosis (ST). Among the 2418 included patients
      (4630 lesions), a total of 77 (1.7%) final dissections occurred in 67 (2.8%)
      subjects. Dissections were more frequent in longer and complex lesions and in the
      left anterior descending, and were associated with increased rates of in-hospital
      (11.9 vs. 5.2%, P=0.017) and 1-month MACE (13.4 vs. 6.0%, P=0.013), with similar
      6-month trends. Cumulative ST was also greater in patients with dissections (6.3
      vs. 1.3%, P=0.011). Even non-obstructive dissections with thrombolysis in
      myocardial infarction 3 flow conferred a significantly worse prognosis.
      CONCLUSION: This study, reporting for the first time on incidence, predictors,
      and outcomes of residual dissections in DES-treated coronary lesions,
      demonstrates their adverse clinical impact and supports the pursuit of a strategy
      of sealing dissection flaps with other DES.

PMID- 16284206
TI  - Cor triventriculare with pericardial aplasia and mitral valve prolapse: a novel
      congenital dysplastic syndrome?

PMID- 16284207
TI  - Three-dimensional visualization of severe pericardial calcification in
      constrictive pericarditis using multidetector-row computed tomography.

PMID- 16284208
TI  - Sedative hypnotics in older people with insomnia: meta-analysis of risks and
      benefits.
AB  - OBJECTIVES: To quantify and compare potential benefits (subjective reports of
      sleep variables) and risks (adverse events and morning-after psychomotor
      impairment) of short term treatment with sedative hypnotics in older people with
      insomnia. DATA SOURCES: Medline, Embase, the Cochrane clinical trials database,
      PubMed, and PsychLit, 1966 to 2003; bibliographies of published reviews and meta
      analyses; manufacturers of newer sedative hypnotics (zaleplon, zolpidem,
      zopiclone) regarding unpublished studies. SELECTION CRITERIA: Randomised
      controlled trials of any pharmacological treatment for insomnia for at least five
      consecutive nights in people aged 60 or over with insomnia and otherwise free of
      psychiatric or psychological disorders. RESULTS: 24 studies (involving 2417
      participants) with extractable data met inclusion and exclusion criteria. Sleep
      quality improved (effect size 0.14, P < 0.05), total sleep time increased (mean
      25.2 minutes, P < 0.001), and the number of night time awakenings decreased
      (0.63, P < 0.001) with sedative use compared with placebo. Adverse events were
      more common with sedatives than with placebo: adverse cognitive events were 4.78
      times more common (95% confidence interval 1.47 to 15.47, P < 0.01); adverse
      psychomotor events were 2.61 times more common (1.12 to 6.09, P > 0.05), and
      reports of daytime fatigue were 3.82 times more common (1.88 to 7.80, P < 0.001)
      in people using any sedative compared with placebo. CONCLUSIONS: Improvements in
      sleep with sedative use are statistically significant, but the magnitude of
      effect is small. The increased risk of adverse events is statistically
      significant and potentially clinically relevant in older people at risk of falls
      and cognitive impairment. In people over 60, the benefits of these drugs may not
      justify the increased risk, particularly if the patient has additional risk
      factors for cognitive or psychomotor adverse events.

PMID- 16284209
TI  - How does progress towards the child mortality millennium development goal affect
      inequalities between the poorest and least poor? Analysis of Demographic and
      Health Survey data.

PMID- 16284210
TI  - Dopamine regulation of amiloride-sensitive sodium channels in lung cells.
AB  - Dopamine increases lung fluid clearance. This is partly due to activation of
      basolateral Na-K-ATPase. However, activation of Na-K-ATPase by itself is unlikely
      to produce large changes in transepithelial transport. Therefore, we examined
      apical and basolateral dopamine's effect on apical, highly selective sodium
      channels [epithelial sodium channels (ENaC)] in monolayers of an alveolar type 2
      cell line (L2). Dopamine increased channel open probability (P(o)) without
      changing the unitary current. The D(1) receptor blocker SCH-23390 blocked the
      dopamine effect, but the D(2) receptor blocker sulpiride did not. The dopamine
      mediated increase in ENaC activity was not a secondary effect of dopamine
      stimulation of Na-K-ATPase, since ouabain applied to the basolateral surface to
      block the activity of Na-K-ATPase did not alter dopamine-mediated ENaC activity.
      Protein kinase A (PKA) was not responsible for dopamine's effect since a PKA
      inhibitor, H89, did not reduce dopamine's effect. However, cpt-2-O-Me-cAMP, which
      selectively binds and activates EPAC (exchange protein activated by cAMP) but not
      PKA, increased ENaC P(o). An Src inhibitor, PP2, and the phosphatidylinositol-3
      kinase inhibitor, LY-294002, blocked dopamine's effect on ENaC. In addition, an
      MEK blocker, U0126, an inhibitor of phospholipase A(2), and a protein phosphatase
      inhibitor also blocked the effect of dopamine on ENaC P(o). Finally, since the
      cAMP-EPAC-Rap1 pathway also activates DARPP32 (32-kDa dopamine response protein
      phosphatase), we confirmed that dopamine phosphorylates DARPP32, and okadaic
      acid, which blocks phosphatases (DARPP32), also blocks dopamine's effect. In
      summary, dopamine increases ENaC activity by a cAMP-mediated alternative
      signaling pathway involving EPAC and Rap1, signaling molecules usually associated
      with growth-factor-activated receptors.

PMID- 16284211
TI  - Inhibition of phosphodiesterase 1 augments the pulmonary vasodilator response to
      inhaled nitric oxide in awake lambs with acute pulmonary hypertension.
AB  - Phosphodiesterase 1 (PDE1) modulates vascular tone and the development of
      tolerance to nitric oxide (NO)-releasing drugs in the systemic circulation. Any
      role of PDE1 in the pulmonary circulation remains largely uncertain. We measured
      the expression of genes encoding PDE1 isozymes in the pulmonary vasculature and
      examined whether or not selective inhibition of PDE1 by vinpocetine attenuates
      pulmonary hypertension and augments the pulmonary vasodilator response to inhaled
      NO in lambs. Using RT-PCR, we detected PDE1A, PDE1B, and PDE1C mRNAs in pulmonary
      arteries and veins isolated from healthy lambs. In 13 lambs, the thromboxane A(2)
      analog U-46619 was infused intravenously to increase mean pulmonary arterial
      pressure to 35 mmHg. Four animals received an intravenous infusion of vinpocetine
      at incremental doses of 0.3, 1, and 3 mg.kg(-1).h(-1). In nine lambs, inhaled NO
      was administered in a random order at 2, 5, 10, and 20 ppm before and after an
      intravenous infusion of 1 mg.kg(-1).h(-1) vinpocetine. Administration of
      vinpocetine did not alter pulmonary and systemic hemodynamics or transpulmonary
      cGMP or cAMP release. Inhaled NO selectively reduced mean pulmonary arterial
      pressure, pulmonary capillary pressure, and pulmonary vascular resistance index,
      while increasing transpulmonary cGMP release. The addition of vinpocetine
      enhanced pulmonary vasodilation and transpulmonary cGMP release induced by NO
      breathing without causing systemic vasodilation but did not prolong the duration
      of pulmonary vasodilation after NO inhalation was discontinued. Our findings
      demonstrate that selective inhibition of PDE1 augments the therapeutic efficacy
      of inhaled NO in an ovine model of acute chemically induced pulmonary
      hypertension.

PMID- 16284212
TI  - Peroxynitrite mediates TNF-alpha-induced endothelial barrier dysfunction and
      nitration of actin.
AB  - We tested the hypothesis that tumor necrosis factor (TNF)-alpha induces a
      peroxynitrite (ONOO(-))-dependent increase in permeability of pulmonary
      microvessel endothelial monolayers (PMEM) that is associated with generation of
      nitrated beta-actin (NO(2)-beta-actin). The permeability of PMEM was assessed by
      the clearance rate of Evans blue-labeled albumin. beta-Actin was extracted from
      PMEM lysate with a DNase-Sepharose column. The extracted beta-actin was
      quantified in terms of its nitrotyrosine/beta-actin ratio with anti-nitrotyrosine
      and anti-beta-actin antibodies, sequentially, by dot-blot assays. The cellular
      compartmentalization of NO(2)-beta-actin was displayed by showing confocal
      localization of nitrotyrosine-immunofluorescence with beta-actin
      immunofluorescence but not with F-actin fluorescence. Incubation of PMEM with TNF
      (100 ng/ml) for 0.5 and 4.0 h resulted in increases in permeability to albumin.
      There was an increase in the nitrotyrosine/beta-actin ratio at 0.5 h with minimal
      association of the NO(2)-beta-actin with F-actin polymers. The TNF-induced
      increase in the nitrotyrosine/beta-actin ratio and permeability were prevented by
      the anti-ONOO(-) agent Urate. The data indicate that TNF induces an ONOO(-)
      dependent barrier dysfunction, which is associated with the generation of NO(2)
      beta-actin.

PMID- 16284213
TI  - Zinc modulates airway epithelium susceptibility to death receptor-mediated
      apoptosis.
AB  - The accelerated loss of lung epithelium through activation of extrinsic apoptosis
      is believed to play a causative role in lung pathogenesis. Previous
      investigations have shown that zinc is required to sustain lung epithelial cell
      viability under stress conditions and that depletion of intracellular zinc
      predisposes cells to apoptosis. In this investigation, we determined whether
      intracellular zinc deficiency enhanced the susceptibility of primary,
      differentiated cultures of human lung epithelium to death receptor-mediated
      apoptosis, leading to barrier dysfunction. Cultures obtained from multiple donors
      were exposed to stimuli that provoke death receptor-mediated apoptosis and
      depleted of intracellular zinc with a zinc-specific chelating agent.
      Transepithelial resistance, paracellular transport, caspase-8 and caspase-3
      activity, and apoptosis were measured. Activation of extrinsic apoptosis or zinc
      chelation alone resulted in a nominal increase in caspase function and apoptosis
      without major evidence of barrier disruption. Activation of extrinsic apoptosis
      in addition to zinc depletion resulted in an abrupt decrease in transepithelial
      resistance, a substantial increase in apoptosis, and an increased paracellular
      leak. Cultures were rescued by supplementation with zinc sulfate. Further
      analysis revealed that exogenous zinc facilitates cell survival through
      activation of the phosphatidylinositol 3-kinase/Akt signaling pathway. We
      conclude that intracellular zinc is a vital factor in lung epithelium that
      protects cells from death receptor-mediated apoptosis and barrier dysfunction.

PMID- 16284214
TI  - Protective effect of endogenous beta-adrenergic tone on lung fluid balance in
      acute bacterial pneumonia in mice.
AB  - Some investigators have reported that endogenous beta-adrenoceptor tone can
      provide protection against acute lung injury. Therefore, we tested the effects of
      beta-adrenoceptor inhibition in mice with acute Escherichia coli pneumonia. Mice
      were pretreated with propranolol or saline and then intratracheally instilled
      with live E. coli (10(7) colony-forming units). Hemodynamics, arterial blood
      gases, plasma catecholamines, extravascular lung water, lung permeability to
      protein, bacterial counts, and alveolar fluid clearance were measured. Acute E.
      coli pneumonia was established after 4 h with histological evidence of acute
      pulmonary inflammation, arterial hypoxemia, a threefold increase in lung vascular
      permeability, and a 30% increase in extravascular lung water as an increase in
      plasma catecholamine levels. beta-Adrenoceptor inhibition resulted in a marked
      increase in extravascular lung water that was explained by both an increase in
      lung vascular permeability and a reduction in net alveolar fluid clearance. The
      increase in extravascular lung water with propranolol pretreatment was not
      explained by an increase in systemic or vascular pressures. The increase in lung
      vascular permeability was explained in part by anti-inflammatory effects of beta
      adrenoceptor stimulation because plasma macrophage inflammatory protein-2 levels
      were higher in the propranolol pretreatment group compared with controls. The
      decrease in alveolar fluid clearance with propranolol was explained by a decrease
      in catecholamine-stimulated fluid clearance. Together, these results indicate
      that endogenous beta-adrenoceptor tone has a protective effect in limiting
      accumulation of extravascular lung water in acute severe E. coli pneumonia in
      mice by two mechanisms: 1) reducing lung vascular injury and 2) upregulating the
      resolution of alveolar edema.

PMID- 16284215
TI  - Oxygen tension modulates the expression of pulmonary vascular BKCa channel alpha-
      and beta-subunits.
AB  - At birth, the lung environment changes from low to relatively high O(2) tension.
      Pulmonary blood flow increases and pulmonary artery pressure decreases. Recent
      data suggest that pulmonary vascular calcium-sensitive K(+) channel (BK(Ca))
      activation mediates perinatal pulmonary vasodilation. Although BK(Ca) channel
      expression is developmentally regulated, the molecular mechanisms responsible for
      BK(Ca) expression remain unknown. We tested the hypothesis that the low-O(2)
      tension environment of the normal fetus modulates BK(Ca) channel expression. We
      analyzed BK(Ca) expression under conditions of hypoxia and normoxia both in vitro
      and in vivo. BK(Ca) alpha-subunit mRNA expression increased twofold in ovine
      pulmonary artery smooth muscle cell (PASMC) primary cultures maintained in
      hypoxia. In vivo, BK(Ca) expression was similarly affected by hypoxia. When adult
      Sprague-Dawley rats were placed in hypobaric hypoxic chambers for 3 wk, hypoxic
      animals showed an increase of threefold in the expression of BK(Ca) alpha- and
      more than twofold in the expression of BK(Ca) beta(1)-subunit mRNA.
      Immunochemical staining was consistent with the genetic data. To assess
      transcriptional activation of the beta-subunit of the BK(Ca), both BK(Ca) beta(1)
      and beta(2)-subunit luciferase (K(Ca) beta:luc(+)) reporter genes were
      constructed. Hypoxia increased PASMC K(Ca) beta(1):luc(+) reporter expression by
      threefold and K(Ca) beta(2):luc(+) expression by 35%. Fetal PASMC treated with
      the hypoxia-inducible factor-1 mimetic deferoxamine showed a 63 and 41% increase
      in BK(Ca) channel alpha- and beta(1)-subunit expression, respectively. Together,
      these results suggest that oxygen tension modulates BK(Ca) channel subunit mRNA
      expression, and the regulation is, at least in part, at the transcriptional
      level.

PMID- 16284216
TI  - Satisfaction surveys: do we really need new questionnaires?

PMID- 16284217
TI  - Neutrophilic inflammation and IL-8 levels in induced sputum of alpha-1
      antitrypsin PiMZ subjects.
AB  - BACKGROUND: Severe alpha-1-antitrypsin deficiency (AATD), due to homozygosity for
      the protease inhibitor (Pi) Z allele, is a genetic risk factor for chronic
      obstructive pulmonary disease (COPD). In a previous study the sputum of severe
      AATD subjects with airflow obstruction showed a pattern of cellular inflammation
      similar to COPD patients. It is uncertain whether heterozygotes for the Z allele
      or intermediate deficiency (PiMZ) have an increased risk of developing COPD.
      METHODS: Sputum cell counts and the supernatant level of the neutrophil
      chemoattractant interleukin (IL)-8 were investigated by sputum induction in 10
      non-smoker asymptomatic PiMZ subjects with normal pulmonary function, 10 patients
      with stable COPD, and 10 age matched normal subjects. Data are expressed as mean
      (SD). RESULTS: The mean (SD) number of neutrophils was significantly higher
      (p<0.01) in the sputum of PiMZ subjects (84.5 (22.2) x10(4)/ml) and patients with
      COPD (126.9 (18.8) x10(4)/ml) than in matched normal subjects (55.0 (8.7)
      x10(4)/ml). IL-8 levels were increased in PiMZ subjects (828.5 (490.6) ng/ml;
      median 1003.0 ng/ml; range 1260-100 ng/ml) and in COPD patients (882.5 (524.3)
      ng/ml; median 934.9 ng/ml; range 1506-258 mg/ml) compared with normal subjects
      (3.5 (0.5) ng/ml; median 3.5 ng/ml; range 4.5-2.5 ng/ml). There was a significant
      positive correlation between IL-8 supernatant concentration and neutrophil count
      in PiMZ subjects (p = 0.036; r = 0.66). An inverse correlation was observed
      between the percentage of neutrophils and forced expiratory volume in 1 second (%
      predicted) in patients with COPD (p = 0.04; r = -0.43). CONCLUSIONS: These
      findings indicate that PiMZ subjects without airflow obstruction may have an IL-8
      related neutrophilic inflammation in the airways, similar to stable COPD
      patients, suggesting an increased risk of developing pulmonary changes.

PMID- 16284218
TI  - Survival impact of epidermal growth factor receptor overexpression in patients
      with non-small cell lung cancer: a meta-analysis.
AB  - BACKGROUND: It is thought that overexpression of epidermal growth factor receptor
      (EGFR) in non-small cell lung cancer (NSCLC) might compromise patient survival,
      presumably by promoting tumour growth by an autocrine mechanism. However,
      conflicting results have been reported from various laboratories, and the
      clinical importance of EGFR overexpression remains unsettled. METHODS: A meta
      analysis of previous studies was performed to quantitatively review the effects
      of EGFR overexpression on survival in patients with NSCLC using a DerSimonian
      Laird random effects model. Eighteen studies including 2972 patients were
      subjected to final analysis. RESULTS: Overall, positivity for EGFR overexpression
      differed between histological types: 39% in adenocarcinomas, 58% in squamous cell
      carcinomas, 38% in large cell carcinomas, and 32% in cancers in a miscellaneous
      category (p<0.0001). The combined hazard ratio (HR) was 1.14 (95% CI 0.97 to
      1.34; p = 0.103), indicating that EGFR overexpression has no significant impact
      on survival. When only the 15 immunohistochemistry based studies were considered,
      the combined HR was 1.08 (95% CI 0.92 to 1.28; p = 0.356), again suggesting that
      EGFR overexpression has no impact on survival. Heterogeneity testing indicated
      that there was heterogeneity between studies but publication bias was absent,
      which suggests that the summary statistics obtained may approximate the actual
      average. CONCLUSIONS: EGFR overexpression was not associated with poorer survival
      in patients with NSCLC. Specific mutations of the EGFR gene will need further
      study in terms of survival implications.

PMID- 16284219
TI  - Lung cancer in Teesside (UK) and Varese (Italy): a comparison of management and
      survival.
AB  - BACKGROUND: The survival of lung cancer patients in the UK is lower than in other
      similar European countries. The reasons for this are unclear. METHODS: Two areas
      were selected with a similar incidence of lung cancer: Teesside in Northern
      England and Varese in Northern Italy. Data were collected prospectively on all
      new cases of lung cancer diagnosed in the year 2000. Comparisons were made of
      basic demographic characteristics, management, and survival. RESULTS: There were
      268 cases of lung cancer in Teesside and 243 in Varese. Patients in Teesside were
      older (p<0.05), were more likely to have smoked (p<0.001), had a higher
      occupational risk (p<0.001), higher co-morbidity (p<0.05), and poorer performance
      status (p<0.001). Fewer patients in Teesside presented as an incidental finding
      (p<0.001) and the histological confirmation rate was lower than in Varese
      (p<0.01). In Teesside there were more large cell carcinomas (p<0.001), more small
      cell carcinomas (p<0.05), and fewer early stage non-small cell lung cancers
      (p<0.05). The resection rate was lower in Teesside (7% v 24%; p<0.01) and more
      patients received no specific anti-cancer treatment (50% v 25%; p<0.001). Overall
      3 year survival was lower in Teesside (7% v 14%; p<0.001). Surgical resection was
      the strongest multivariate survival predictor in Varese (HR = 0.46) and Teesside
      (HR = 0.31). Co-morbidity in Teesside resulted in a significantly lower resection
      rate (p<0.001). CONCLUSIONS: Patients with lung cancer in Teesside presented at a
      later stage, with more aggressive types of tumour, and had higher co-morbidity
      than patients in Varese. As a result, the resection rate was significantly lower
      and survival was worse.

PMID- 16284220
TI  - Inflammatory markers are associated with ventilatory limitation and muscle
      dysfunction in obstructive lung disease in well functioning elderly subjects.
AB  - BACKGROUND: Inflammatory markers are increased in chronic obstructive pulmonary
      disease (COPD) and are hypothesised to play an important part in muscle
      dysfunction and exercise intolerance. METHODS: The Health Aging and Body
      Composition (Health ABC) study is a prospective observational cohort of well
      functioning individuals aged 70-79 years. A cross sectional analysis of the
      baseline data was conducted to examine the association between inflammatory
      markers and ventilatory limitation, muscle strength, and exercise capacity. These
      associations were compared in participants with and without obstructive lung
      disease (OLD). RESULTS: Of the 3075 participants enrolled in the Health ABC
      cohort, OLD was identified by spirometric testing in 268 participants and 2005
      participants had normal spirometric results. Of the participants with OLD, 35%,
      38%, and 27% participants had mild, moderate, and severe OLD, respectively.
      Participants with OLD had lower quadriceps strength (102.5 Nm v 108.9 Nm, p =
      0.02), lower maximum inspiratory pressure (64.7 cm H(2)O v 74.2 cm H(2)O,
      p<0.0001), higher systemic interleukin (IL)-6 levels (2.6 pg/ml v 2.2 pg/ml,
      p<0.0001), and higher C-reactive protein (CRP) levels (3.5 mg/l v 2.5 mg/l,
      p<0.0001) than those with normal spirometry. In participants with OLD and those
      with normal spirometry, forced expiratory volume in 1 second (FEV(1)) was
      associated with IL-6 (adjusted regression coefficients (beta) = -5.3 (95% CI -9.1
      to-1.5) and -3.1 (95% CI -4.3 to -1.9), respectively). IL-6 and TNF were also
      associated with quadriceps strength among participants with OLD and those with
      normal spirometry (beta = -6.4 (95% CI -12.8 to -0.03) and -3.4 (95% CI -5.4 to 
      1.3), respectively, for IL-6 and beta = -10.1 (95% CI -18.7 to -1.5) and -3.8
      (95% CI -7 to -0.6), respectively, for TNF). IL-6, quadriceps strength, and
      maximum inspiratory pressures were independent predictors of reduced exercise
      capacity in both groups. CONCLUSIONS: In well functioning elderly subjects with
      or without OLD, IL-6 is associated with reduced FEV(1), quadriceps strength, and
      exercise capacity.

PMID- 16284221
TI  - Usefulness of transoesophageal echocardiography before cardioversion in patients
      with atrial fibrillation and different anticoagulant regimens.
AB  - OBJECTIVES: To evaluate the prevalence of atrial thrombi in patients with atrial
      fibrillation undergoing different anticoagulation regimens before cardioversion;
      to evaluate the usefulness of transoesophageal echocardiography (TOE) guided
      cardioversion to prevent thromboembolic complications; and to correlate the
      presence of atrial thrombi with clinical and echocardiographic data. METHODS: 757
      consecutive patients admitted as candidates for cardioversion of atrial
      fibrillation were enrolled in the study. They were divided into four groups:
      effective conventional oral anticoagulation, short term anticoagulation,
      ineffective oral anticoagulation or subtherapeutic anticoagulation, and effective
      oral anticoagulation with a duration of < 3 weeks for various clinical reasons.
      All patients underwent TOE before cardioversion; in the presence of atrial
      thrombi or extreme left atrial echo contrast, cardioversion was postponed. The
      incidence of thromboembolic events was evaluated after cardioversion. RESULTS:
      Atrial thrombi were detected in 48 of the 757 (6.3%) patients. No significant
      differences in the percentage of atrial thrombosis were found in the four study
      groups. Patients with atrial thrombosis were older and had a higher percentage of
      mitral prosthetic valves, lower left ventricular ejection fraction, more severe
      atrial spontaneous echo contrast, and lower Doppler left atrial appendage
      velocities. 648 patients were scheduled for cardioversion. Cardioversion was
      successful in 89% of patients without any major thromboembolic event.
      CONCLUSIONS: The prevalence of atrial thrombosis before cardioversion despite
      different treatments with anticoagulants is about 7% and a TOE guided approach
      may prevent the risk of embolic events.

PMID- 16284222
TI  - Transcatheter closure of atrial septal defects improves right ventricular volume,
      mass, function, pulmonary pressure, and functional class: a magnetic resonance
      imaging study.
AB  - OBJECTIVE: To characterise prospectively by magnetic resonance imaging (MRI)
      changes in right ventricular (RV) volume, function, and mass after transcatheter
      closure of atrial septal defects (ASDs) and to evaluate the course of pulmonary
      pressure and functional class criteria. METHODS: In 20 patients with secundum
      type ASD and dilated RV diameter, MRI was performed to quantify RV end diastolic
      (RVEDV) and end systolic volumes (RVESV), RV mass, tricuspid annular diameter,
      and RV ejection fraction before and 6 and 12 months after transcatheter closure
      of the ASD. RV systolic pressure was measured during follow up by transthoracic
      echocardiography. RESULTS: Functional class improved in the majority of patients
      after ASD closure. RVESV (from 81 (18) ml/m2 to 53 (15) ml/m2, p < 0.001), RVEDV
      (from 127 (17) ml/m2 to 99 (18) ml/m2, p < 0.001), and RV mass (from 79 (10) g to
      63 (8) g, p < 0.01) decreased significantly during follow up, although tricuspid
      annular diameter did not. RV ejection fraction improved (by 9% compared with
      baseline, p < 0.05) and RV systolic pressure decreased significantly (from 33 (8)
      mm Hg to 24 (6) mm Hg, p < 0.001) after closure. CONCLUSION: MRI studies showed
      significant improvement of RV volumes, mass, and function after transcatheter
      closure of ASDs. Restoration of the RV leads to decreased pulmonary pressure
      resulting in a better functional class in the majority of patients.

PMID- 16284223
TI  - HIV infection in older patients in the HAART era.
AB  - An increasing number of patients over 50 years of age are now living with HIV,
      owing to highly active antiretroviral therapy (HAART) that prolongs survival on
      the one hand and to late diagnosis of patients living with occult HIV infection
      on the other hand. Most studies have shown that compared with younger patients,
      patients over 50 generally have a slower immunological response to HAART and
      experience more rapid clinical progression, despite a better virological
      response. Low thymic output probably plays a role in the poorer CD4 cell response
      in patients initiating HAART over 50 years. Management of HIV infection in older
      patients is particularly complex, mainly because they are more likely to have co
      morbidities necessitating specific medications that may interact with
      antiretroviral drugs. More controlled studies of HAART efficacy and tolerability
      in such patients are needed to establish specific management guidelines.
      Information campaigns targeting older patients and their doctors are also needed
      to ensure timely diagnosis of HIV infection and antiretroviral treatment
      initiation.

PMID- 16284224
TI  - Rapid detection of clarithromycin resistance in Helicobacter pylori using a PCR
      based denaturing HPLC assay.
AB  - OBJECTIVES: We evaluated a new approach for the rapid detection of clarithromycin
      resistance in Helicobacter pylori, based on PCR and denaturing HPLC (DHPLC).
      METHODS: A 180 bp fragment of the 23S rRNA gene was amplified using DNA from 81
      clinical H. pylori isolates (51 isolates were shown to be resistant to
      clarithromycin by Etest), and, directly, from 101 gastric biopsies from patients
      with digestive diseases, who were infected with H. pylori as assessed by a 13C
      urea breath test, histology and/or culture. DHPLC was used to detect mutations in
      all the PCR products. RESULTS: DHPLC profiles for the 30 susceptible isolates all
      showed homoduplex peaks; the resistant isolates consistently generated
      heteroduplex peaks that were easily distinguishable from the wild-type H. pylori
      reference strain. Sequencing revealed point mutations in all the resistant
      isolates. Overall, five different mutations were detected. Four of these
      mutations (A2142G, A2142C, A2143G and T2182C) are known to be associated with
      clarithromycin resistance; the remaining mutation (C2195T) has not been
      previously described. This novel single-base substitution was found in
      combination with the common mutation A2143G. Of the biopsies tested, 25 specimens
      generated heteroduplexes due to sequence alterations (mutation A2142G, A2142C or
      A2143G). In one of these specimens, A2143G was found together with the novel
      mutation T2221C; in another, a mixture of wild-type and mutant (A2143G) sequences
      was detected. For 20 culture-positive out of the 25 biopsies DHPLC results
      confirmed the presence of clarithromycin resistance. CONCLUSIONS: Our results
      suggest that the PCR-DHPLC assay is a valid tool for rapid assessment of
      clarithromycin resistance in H. pylori and that in the future it could be used
      directly on biopsy specimens, avoiding the need for culture-based methods.

PMID- 16284225
TI  - Arterial compliance of rowers: implications for combined aerobic and strength
      training on arterial elasticity.
AB  - Regular endurance exercise increases central arterial compliance, whereas
      resistance training decreases it. It is not known how the vasculature adapts to a
      combination of endurance and resistance training. Rowing is unique, because its
      training encompasses endurance- and strength-training components. We used a cross
      sectional study design to determine arterial compliance of 15 healthy, habitual
      rowers [50 +/- 9 (SD) yr, 11 men and 4 women] and 15 sedentary controls (52 +/- 8
      yr, 10 men and 5 women). Rowers had been training 5.4 +/- 1.2 days/wk for 5.7 +/-
      4.0 yr. The two groups were matched for age, body composition, blood pressure,
      and metabolic risk factors. Central arterial compliance (simultaneous ultrasound
      and applanation tonometry on the common carotid artery) was higher (P < 0.001)
      and carotid beta-stiffness index was lower (P < 0.001) in rowers than in
      sedentary controls. There were no group differences for measures of peripheral
      (femoral) arterial stiffness. The higher central arterial compliance in rowers
      was associated with a greater cardiovagal baroreflex sensitivity, as estimated
      during a Valsalva maneuver (r = 0.54, P < 0.005). In conclusion, regular rowing
      exercise in middle-aged and older adults is associated with a favorable effect on
      the elastic properties of the central arteries. Our results suggest that
      simultaneously performed endurance training may negate the stiffening effects of
      strength training.

PMID- 16284226
TI  - Impaired left ventricular filling due to right-to-left ventricular interaction in
      patients with pulmonary arterial hypertension.
AB  - The aim of this study was to investigate the contribution of direct right-to-left
      ventricular interaction to left ventricular filling and stroke volume in 46
      patients with pulmonary arterial hypertension (PAH) and 18 control subjects.
      Stroke volume, right and left ventricular volumes, left ventricular filling rate,
      and interventricular septum curvature were measured by magnetic resonance imaging
      and left atrial filling by transesophageal echocardiography. Stroke volume, left
      ventricular end-diastolic volume, and left ventricular peak filling rate were
      decreased in PAH patients compared with control subjects: 28 +/- 13 vs. 41 +/- 10
      ml/m(2) (P < 0.001), 46 +/- 14 vs. 61 +/- 14 ml/m(2) (P < 0.001), and 216 +/- 90
      vs. 541 +/- 248 ml/s (P < 0.001), respectively. Among PAH patients, stroke volume
      did not correlate to right ventricular end-diastolic volume or mean pulmonary
      arterial pressure but did correlate to left ventricular end-diastolic volume (r =
      0.62, P < 0.001). Leftward interventricular septum curvature was correlated to
      left ventricular filling rate (r = 0.64, P < 0.001) and left ventricular end
      diastolic volume (r = 0.65, P < 0.001). In contrast, left atrial filling was
      normal and not correlated to left ventricular end-diastolic volume. In PAH
      patients, ventricular interaction mediated by the interventricular septum impairs
      left ventricular filling, contributing to decreased stroke volume.

PMID- 16284227
TI  - Age-associated impairment in vasorelaxation to fluid shear stress in the female
      vasculature is improved by TNF-alpha antagonism.
AB  - Aging is associated with alterations in vascular homeostasis, including a
      reduction in flow-mediated vasodilation, which in women is related to the onset
      of menopause. We previously found that in female animals, aging is associated
      with an increase in TNF-alpha. Thus we investigated the role of in vivo TNF-alpha
      inhibition on vascular responses to shear stress in aging female rats. Mesenteric
      arteries (approximately 150 microm) were isolated from young (3 mo) and
      ovariectomized Sprague-Dawley female rats approaching reproductive senescence (12
      mo) treated with either placebo or a TNF-alpha inhibitor (etanercept; 0.3 mg/kg)
      and were mounted on a pressure myograph system. Vessels were equilibrated at an
      intraluminal pressure of 60 mmHg and then preconstricted with phenylephrine at
      approximately 70% of their initial diameter. Perfusate flow was increased in
      steps from 0 to 150 microl/min. Compared with young vessels, aged vessels have a
      decrease in flow-mediated dilation [maximal dilation (means +/- SE): 52 +/- 4 vs.
      24 +/- 15%; P < 0.05], which was improved by TNF-alpha inhibition. Moreover, in
      aged vessels maximal dilation to flow was achieved at higher levels of shear
      stress compared with young vessels. In all groups, flow-mediated dilation was
      abolished by either endothelial removal or nitric oxide synthase inhibition with
      N(G)-nitro-L-arginine methyl ester. However, the modulation by N(G)-nitro-L
      arginine methyl ester was reduced in vessels from aged animals compared with
      young animals but was improved in the etanercept-treated aged animals. In vivo
      chronic TNF-alpha inhibition improves flow-mediated arterial dilation in
      resistance arteries of aged female animals.

PMID- 16284229
TI  - Exercise training induces respiratory substrate-specific decrease in Ca2+-induced
      permeability transition pore opening in heart mitochondria.
AB  - The purpose of this study was to determine whether regular exercise (treadmill
      running, 10 wk) alters the susceptibility of rat isolated heart mitochondria to
      Ca(2+)-induced permeability transition pore (PTP) opening and whether this could
      be associated with changes in the modulation of PTP opening by selected
      physiological effectors. Basal leak-driven and ADP-stimulated respiration in the
      presence of substrates for complex I, II, and IV were not affected by training.
      Fluorimetric studies revealed that in the control and exercise-trained groups,
      the amount of Ca(2+) required to trigger PTP opening was greater in the presence
      of complex II vs. I substrates (230 +/- 12 vs. 134 +/- 7 nmol Ca(2+)/mg protein,
      P < 0.01; pooled average of control and trained groups). In addition, with a
      substrate feeding the complex II, training increased by 45% (P < 0.01) the amount
      of Ca(2+) required to trigger PTP opening both in the presence and absence of the
      PTP inhibitor cyclosporin A. However, membrane potential, reactive oxygen species
      production, NAD(P)H ratio, and Ca(2+) uptake kinetics were not different in
      mitochondria from both groups. Together, these results suggest the existence of a
      substrate-specific regulation of the PTP in heart mitochondria and suggest that
      regular exercise results in a reduced sensitivity to Ca(2+)-induced PTP opening
      in presence of complex II substrates.

PMID- 16284228
TI  - Connexin40 and connexin43 in mouse aortic endothelium: evidence for coordinated
      regulation.
AB  - In the vessel wall, endothelial cells are metabolically and electrically coupled
      to each other and to the adjacent smooth muscle cells by gap junctions composed
      of connexins. Gap junctions may be formed from combinations of several different
      connexin proteins, and deletion of one connexin can lead to modification of the
      expression of another. To reveal a possible interaction between connexin40 (Cx40)
      and connexin43 (Cx43) in endothelium, we studied their distribution in vessels
      from C57Bl/6 and Cx40 knockout mice (Cx40-/-) using immunoblots and
      immunocytochemistry on aortic cross sections and en face whole mounts. En face
      preparations from C57Bl/6 mice revealed two distinct pools of Cx43, one
      pericellular and the other intracellular. Cx40 was largely restricted to the
      periphery of the cells, and in Cx40-/- mice it was, as expected, undetectable. In
      the Cx40-/- mice, total Cx43 protein was also modestly reduced (immunoblots), but
      there was a major redistribution of the protein within the cell. The pericellular
      component of Cx43 was rendered virtually undetectable, and the intracellular
      compartments were normal or even slightly elevated. Smooth muscle Cx43 was also
      reduced in the Cx40-/- animals. These findings indicate that the cellular
      distribution of Cx43 is dependent on the presence of Cx40, and in view of the
      profound effects on the pericellular pool of the Cx43, the findings suggest that
      interactions between Cx40 and Cx43 regulate communication between endothelial
      cells and perhaps between smooth muscle and endothelial cells as well.

PMID- 16284230
TI  - Relationship among diastolic intraventricular pressure gradients, relaxation, and
      preload: impact of age and fitness.
AB  - Diastolic intraventricular pressure gradients (IVPGs) are a measure of the
      ability of the ventricle to facilitate its filling using diastolic suction. We
      assessed 15 healthy young but sedentary subjects, aged <50 yr (young subjects;
      age, 35 +/- 9 yr); 13 healthy but sedentary seniors, aged >65 yr with known
      reductions in ventricular compliance (elderly sedentary subjects; age, 70 +/- 4
      yr); and 12 master athletes, aged >65 yr, previously shown to have preserved
      ventricular compliance (elderly fit subjects; age, 68 +/- 3 yr). Pulmonary
      capillary wedge pressure (PCWP) and echocardiography measurements were performed
      at baseline, during load manipulation by lower body negative pressure at -15 and 
      30 mmHg, and after saline infusion of 10 and 20 ml/kg (elderly) or 15 and 30
      ml/kg (young). IVPGs were obtained from color M-mode Doppler echocardiograms.
      Baseline IVPGs were lower (1.2 +/- 0.4 vs. 2.4 +/- 0.7 mmHg, P < 0.0001), and the
      time constant of pressure decay (tau(0)) was longer (60 +/- 10 vs. 46 +/- 6 ms, P
      < 0.0001) in elderly sedentary than in young subjects, with no difference in
      PCWP. Although PCWP changes during load manipulations were similar (P = 0.70),
      IVPG changes were less prominent in elderly sedentary than in young subjects (P =
      0.02). Changes in stroke volume and IVPGs during loading manipulations correlated
      (r = 0.96, P = 0.0002). PCWP and tau(0) were strong multivariate correlates of
      IVPGs (P < 0.001, for both). IVPG response to loading interventions in elderly
      sedentary and elderly fit subjects was similar (P = 0.33), despite known large
      differences in ventricular compliance. The ability to regulate IVPGs during
      changes in preload is impaired with aging. Preserving ventricular compliance
      during aging by lifelong exercise training does not prevent this impairment.

PMID- 16284231
TI  - Lowering of interstitial fluid pressure in rat submandibular gland: a novel
      mechanism in saliva secretion.
AB  - The submandibular gland transports fluid at a high rate through the interstitial
      space during salivation, but the exact level of all forces governing
      transcapillary fluid transport has not been established. In this study, our aim
      was to measure the relation between interstitial fluid volume (V(i)) and
      interstitial fluid pressure (P(if)) in salivary glands during active secretion
      and after systemically induced passive changes in gland hydration. We tested
      whether interstitial fluid could be isolated by tissue centrifugation to enable
      measurement of interstitial fluid colloid osmotic pressure. During control
      conditions, V(i) averaged 0.23 ml/g wet wt (SD 0.014), with a corresponding mean
      P(if) measured with micropipettes of 3.0 mmHg (SD 1.3). After induction of
      secretion by pilocarpine, P(if) dropped by 3.8 mmHg (SD 1.5) whereas V(i) was
      unchanged. During dehydration and overhydration of up to 20% increase of V(i)
      above control, a linear relation was found between volume and pressure, resulting
      in a compliance (DeltaV(i)/DeltaP(if)) of 0.012 ml.g wet wt(-1).mmHg(-1).
      Interstitial fluid was isolated, and interstitial fluid colloid osmotic pressure
      averaged 10.4 mmHg (SD 1.2), which is 64% of the corresponding level in plasma.
      We conclude that P(if) drops during secretion and, thereby, increases the net
      transcapillary pressure gradient, a condition that favors fluid filtration and
      increases the amount of fluid available for secretion. The reduction in P(if) is
      most likely induced by contraction of myoepithelial cells and suggests an active
      and new role for these cells in salivary secretion. The relatively low
      interstitial compliance of the organ will enhance the effect of the myoepithelial
      cells on P(if) during reduced V(i).

PMID- 16284232
TI  - Effect of angiotensin II receptor blockade on autonomic nervous system function
      in patients with essential hypertension.
AB  - It has long been proposed that the renin-angiotensin system exerts a stimulatory
      influence on the sympathetic nervous system, including augmentation of central
      sympathetic outflow and presynaptic facilitation of norepinephrine release from
      sympathetic nerves. We tested this proposition in 19 patients with essential
      hypertension, evaluating whether the angiotensin receptor blockers (ARBs)
      eprosartan and losartan had identifiable antiadrenergic properties. This was done
      in a prospective, randomized, three-way placebo-controlled study of crossover
      design. Patients were randomized to 600 mg of eprosartan daily, 50 mg of losartan
      daily, or placebo. The treatment period was 4 wk, with 2-wk washout periods.
      Multiunit firing rates in efferent sympathetic nerves distributed to skeletal
      muscle vasculature (muscle sympathetic nerve activity, MSNA) were measured with
      microneurography, testing whether ARBs inhibit central sympathetic outflow. In
      parallel, isotope dilution methodology was used to measure whole body
      norepinephrine spillover to plasma. Mean blood pressure on placebo was 151/98
      mmHg, with both ARBs causing reductions of approximately 11 mmHg systolic and 6
      mmHg diastolic pressure, placebo corrected. Both MSNA [35 +/- 12 bursts/min (mean
      +/- SD) on placebo] and whole body norepinephrine spillover [366 +/- 247 ng/min]
      were unchanged by ARB administration, indicating that the ARBs did not materially
      inhibit central sympathetic outflow or act presynaptically to reduce
      norepinephrine release at existing rates of nerve firing. These findings contrast
      with the easily demonstrable reduction in sympathetic nervous activity produced
      by antihypertensive drugs of the imidazoline-binding class, which are known to
      act within the brain to inhibit sympathetic nervous outflow. We conclude that
      sympathetic nervous inhibition is not a major component of the blood pressure
      lowering action of ARBs in essential hypertension.

PMID- 16284233
TI  - Stimulation of A2A-adenosine receptors after myocardial infarction suppresses
      inflammatory activation and attenuates contractile dysfunction in the remote left
      ventricle.
AB  - Following myocardial infarction (MI), contractile dysfunction develops not only
      in the infarct zone but also in noninfarcted regions of the left ventricle remote
      from the infarct zone. Inflammatory activation secondary to MI stimulates
      inducible nitric oxide synthase (iNOS) induction with excess production of nitric
      oxide. We hypothesized that the anti-inflammatory effects of selective A(2A)
      adenosine receptor (A(2A)AR) stimulation would suppress inflammation and preserve
      cardiac function in the remote zone early after MI. A total of 53 mice underwent
      60 min of coronary occlusion followed by 24 h of reperfusion. The A(2A)AR agonist
      (ATL146e, 2.4 microg/kg) was administered intraperitoneally 1, 3, and 6 h
      postreperfusion. Because of the 1-h delay in treatment after MI, ATL146e had no
      effect on infarct size, as demonstrated by contrast-enhanced cardiac MRI (n = 18)
      performed 24 h post-MI. ATL146e did however preserve global cardiac function at
      that time by limiting contractile dysfunction in remote regions [left ventricle
      wall thickening: 51 +/- 4% in treated (n = 9) vs. 29 +/- 3% in nontreated groups
      (n = 9), P < 0.01]. RT-PCR, immunohistochemistry, and Western blot analysis
      indicated that iNOS mRNA and protein expression were significantly reduced by
      ATL146e treatment in both infarcted and noninfarcted zones. Similarly, elevations
      in plasma nitrate-nitrite after MI were substantially blunted by ATL146e (P <
      0.01). Finally, treatment with ATL146e reduced NF-kappaB activation in the
      myocardium by over 50%, not only in the infarct zone but also in noninfarcted
      regions (P < 0.05). In conclusion, A(2A)AR stimulation after MI suppresses
      inflammatory activation and preserves cardiac function, suggesting the potential
      utility of A(2A)AR agonists against acute heart failure in the immediate post-MI
      period.

PMID- 16284234
TI  - Time-dependent modulation of arterial baroreflex control of muscle sympathetic
      nerve activity during isometric exercise in humans.
AB  - We investigated the time-dependent modulation of arterial baroreflex (ABR)
      control of muscle sympathetic nerve activity (MSNA) that occurs during isometric
      handgrip exercise (IHG). Thirteen healthy subjects performed a 3-min IHG at 30%
      maximal voluntary contraction, which was followed by a period of imposed
      postexercise muscle ischemia (PEMI). The ABR control of MSNA (burst incidence and
      strength and total activity) was evaluated by analyzing the relationship between
      spontaneous variations in diastolic arterial pressure (DAP) and MSNA during
      supine rest, at each minute of IHG, and during PEMI. We found that 1) the linear
      relations between DAP and MSNA variables were shifted progressively rightward
      until the third minute of IHG (IHG3); 2) 2 min into IHG (IHG2), the DAP-MSNA
      relations were shifted upward and were shifted further upward at IHG3; 3) the
      sensitivity of the ABR control of total MSNA was increased at IHG2 and increased
      further at IHG3; and 4) during PEMI, the ABR operating pressure was slightly
      higher than at IHG2, and the sensitivity of the control of total MSNA was the
      same as at IHG2. During PEMI, the DAP-burst strength and DAP-total MSNA relations
      were shifted downward from the IHG3 level to the IHG2 level, whereas the DAP
      burst incidence relation remained at the IHG3 level. These results indicate that
      during IHG, ABR control of MSNA is modulated in a time-dependent manner. We
      suggest that this modulation of ABR function is one of the mechanisms underlying
      the progressive increase in blood pressure and MSNA during the course of
      isometric exercise.

PMID- 16284235
TI  - Rosuvastatin improves cerebrovascular function in Zucker obese rats by inhibiting
      NAD(P)H oxidase-dependent superoxide production.
AB  - Insulin-resistance induces cerebrovascular dysfunction and increases the risk for
      stroke. We investigated whether rosuvastatin (RSV), a 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitor, can reverse reduced cerebrovascular
      responsiveness in insulin-resistant rats. Dilator responses of the basilar artery
      (BA) were examined after 1-day or 4-wk RSV (2 mg.kg(-1).day(-1)) treatment in
      anesthetized 12-wk-old insulin-resistant Zucker obese (ZO) and lean (ZL) rats by
      using a cranial window preparation. Vehicle-treated ZO rats had significantly
      higher fasting insulin, total cholesterol (TC), and triglyceride (TG) levels
      compared with ZL rats. In addition, in the ZO rats, dilator responses of the BA
      to acetylcholine, iloprost, cromakalim, and potassium chloride were significantly
      reduced when compared with ZL rats. One-day RSV treatment improved dilator
      responses of the ZO BAs without altering lipid levels. Four-week RSV treatment
      lowered both TC and TG by 30% and also improved dilator responses of the ZO BAs,
      although without additional effects compared with the 1-day RSV treatment.
      NAD(P)H oxidase-dependent superoxide production was significantly higher in the
      cerebral arteries of vehicle-treated ZO rats compared with ZL rats, but both 1
      day and 4-wk RSV treatments normalized elevated superoxide levels in the ZO
      arteries. These findings demonstrate that RSV improves cerebrovascular function
      in insulin-resistance independently from its lipid-lowering effect by the
      inhibition of NAD(P)H oxidase.

PMID- 16284236
TI  - Effect of acute sympathetic nervous system activation on flow-mediated dilation
      of brachial artery.
AB  - We tested the hypothesis that flow-mediated dilation (FMD) of the brachial artery
      would be impaired by acute increases in sympathetic nervous system activity (SNA)
      in models where similar peak shear stress stimulus was achieved by varying the
      duration of forearm muscle ischemia. Eleven healthy young men were studied under
      four different conditions, each with its own control: lower body suction (LBS),
      cold pressor test (CPT), mental arithmetic task (MAT), and activation of muscle
      chemoreflex (MCR). The duration of ischemia before observation of FMD by
      ultrasound imaging was 5 min each for control, LBS, and CPT; 3 min for MAT; and 2
      min for MCR. Peak shear rate was not different between control and any of the SNA
      conditions, although total shear in the first minute was reduced in MAT. MCR was
      the only condition in which brachial artery vasoconstriction was observed before
      forearm occlusion [4.38 (SD 0.53) vs. control 4.60 (SD 0.53) mm, P < 0.05];
      however, diameter increased to the same absolute value as that of the control, so
      the percent FMD was greater for MCR [9.85 (SD 2.33) vs. control 5.29 (SD 1.50)%].
      Blunting of the FMD response occurred only in the CPT model [1.51 (SD 1.20)%].
      During SNA, the increase in plasma cortisol from baseline was significant only
      for MCR; the increase in plasma norepinephrine was significant for MCR, LBS, and
      CPT; and the increase in epinephrine was significant only for MCR. These results
      showed that the four models employed to achieve increases in SNA had different
      effects on baseline brachial artery diameter and that blunted FMD is not a
      general response to increased SNA.

PMID- 16284237
TI  - Angiotensin II hypertension is attenuated in interleukin-6 knockout mice.
AB  - Plasma levels of IL-6 correlate with high blood pressure under many
      circumstances, and ANG II has been shown to stimulate IL-6 production from
      various cell types. This study tested the role of IL-6 in mediating the
      hypertension caused by high-dose ANG II and a high-salt diet. Male C57BL6 and IL
      6 knockout (IL-6 KO) mice were implanted with biotelemetry devices and placed in
      metabolic cages to measure mean arterial pressure (MAP), heart rate (HR), sodium
      balance, and urinary albumin excretion. Baseline MAP during the control period
      averaged 114 +/- 1 and 109 +/- 1 mmHg for wild-type (WT) and IL-6 KO mice,
      respectively, and did not change significantly when the mice were placed on a
      high-salt diet (HS; 4% NaCl). ANG II (90 ng/min sc) caused a rapid increase in
      MAP in both groups, to 141 +/- 9 and 141 +/- 4 in WT and KO mice, respectively,
      on day 2. MAP plateaued at this level in KO mice (134 +/- 2 mmHg on day 14 of ANG
      II) but began to increase further in WT mice by day 4, reaching an average of 160
      +/- 4 mmHg from days 10 to 14 of ANG II. Urinary albumin excretion on day 4 of
      ANG II was not different between groups (9.18 +/- 4.34 and 8.53 +/- 2.85 microg/2
      days for WT and KO mice). By day 14, albumin excretion was nearly fourfold
      greater in WT mice, but MAP dropped rapidly back to control levels in both groups
      when the ANG II was stopped after 14 days. Thus the approximately 30 mmHg greater
      ANG II hypertension in the WT mice suggests that IL-6 contributes significantly
      to ANG II-salt hypertension. In addition, the early separation in MAP, the
      albumin excretion data, and the rapid, post-ANG II recovery of MAP suggest an IL
      6-dependent mechanism that is independent of renal injury.

PMID- 16284238
TI  - Synchronous progression of calcium transient-dependent beating and sarcomere
      destruction in apoptotic adult cardiomyocytes.
AB  - During early apoptosis, adult cardiomyocytes show unusual beating, suggesting
      possible participation of abnormal Ca(2+) transients in initiation of apoptotic
      processes in this cell type. Simultaneously with the beating, these cells show
      dynamic structural alteration resulting from cytoskeletal disintegration that is
      quite rapid. Because of the specialized structure and extensive cytoskeleton of
      cardiomyocytes, we hypothesized that its degradation in so short a time would
      require a particularly efficient mechanism. To better understand this mechanism,
      we used serial video microscopy to observe beta-adrenergic stimulation-induced
      apoptosis in isolated adult rat cardiomyocytes while simultaneously recording
      intracellular Ca(2+) concentration and cell length. Trains of Ca(2+) transients
      and corresponding rhythmic contractions and relaxations (beating) were observed
      in apoptotic cells. Frequencies of Ca(2+) transients and beating gradually
      increased with time and were accompanied by cellular shrinkage. As the cells
      shrank, amplitudes of Ca(2+) transients declined and diastolic intracellular
      Ca(2+) concentration increased until the transients were lost. Beating and
      progression of apoptosis were significantly inhibited by antagonists against the
      L-type Ca(2+) channel (nifedipine), ryanodine receptor (ryanodine), inositol
      1,4,5-trisphosphate receptor (heparin), sarco(endo)plasmic Ca(2+)-ATPase
      (thapsigargin), and Na(+)/Ca(2+) exchanger (KB-R7943). Electron-microscopic
      examination of beating cardiomyocytes revealed progressive breakdown of Z disks.
      Immunohistochemical analysis and Western blot confirmed that disappearance of Z
      disk constituent proteins (alpha-actinin, desmin, and tropomyosin) preceded
      degradation of other cytoskeletal proteins. It thus appears that, in adult
      cardiomyocyte apoptosis, Ca(2+) transients mediate apoptotic beating and
      efficient sarcomere destruction initiated by Z disk breakdown.

PMID- 16284239
TI  - Nonlinear isochrones in murine left ventricular pressure-volume loops: how well
      does the time-varying elastance concept hold?
AB  - The linear time-varying elastance theory is frequently used to describe the
      change in ventricular stiffness during the cardiac cycle. The concept assumes
      that all isochrones (i.e., curves that connect pressure-volume data occurring at
      the same time) are linear and have a common volume intercept. Of specific
      interest is the steepest isochrone, the end-systolic pressure-volume relationship
      (ESPVR), of which the slope serves as an index for cardiac contractile function.
      Pressure-volume measurements, achieved with a combined pressure-conductance
      catheter in the left ventricle of 13 open-chest anesthetized mice, showed a
      marked curvilinearity of the isochrones. We therefore analyzed the shape of the
      isochrones by using six regression algorithms (two linear, two quadratic, and two
      logarithmic, each with a fixed or time-varying intercept) and discussed the
      consequences for the elastance concept. Our main observations were 1) the volume
      intercept varies considerably with time; 2) isochrones are equally well described
      by using quadratic or logarithmic regression; 3) linear regression with a fixed
      intercept shows poor correlation (R(2) < 0.75) during isovolumic relaxation and
      early filling; and 4) logarithmic regression is superior in estimating the fixed
      volume intercept of the ESPVR. In conclusion, the linear time-varying elastance
      fails to provide a sufficiently robust model to account for changes in pressure
      and volume during the cardiac cycle in the mouse ventricle. A new framework
      accounting for the nonlinear shape of the isochrones needs to be developed.

PMID- 16284240
TI  - Matrix metalloproteinase expression in vein grafts: role of inflammatory
      mediators and extracellular signal-regulated kinases-1 and -2.
AB  - Matrix metalloproteinases (MMPs) play key roles in vascular remodeling. We
      characterized the role of inflammatory mediators and extracellular signal
      regulated kinases (ERKs) in the control of arterialized vein graft expression of
      MMP-9, MMP-2, and membrane-type 1-MMP (MT1-MMP) and of the tissue inhibitor of
      metalloproteinases-2 (TIMP-2). For this purpose we used a canine model of jugular
      vein to carotid artery interposition graft and analyzed the vein grafts at
      various postoperative times (30 min to 28 days) using the contralateral vein as a
      control. To study the role of ERK-1/2, veins were incubated with the mitogen
      activated protein kinase kinase (MEK-1/2) inhibitor UO126 for 30 min before being
      grafted. Vein graft extracts were analyzed for MMPs, TIMP-2, tumor necrosis
      factor-alpha (TNF-alpha), polymorphonuclear neutrophil (PMN) infiltration,
      myeloperoxidase (MPO), and thrombin activity, and for ERK-1/2 activation. Vein
      graft arterialization resulted in rapid and sustained (8 h to 28 days)
      upregulation of vein graft-associated MMP-9, MMP-2, MT1-MMP, thrombin activity,
      and TNF-alpha levels with concomitant TIMP-2 downregulation. MMP-2 activation
      preceded MT1-MMP upregulation. PMN infiltration and vein graft-associated MPO
      activity increased within hours after arterialization, indicating a prompt, local
      inflammatory response. In cultured smooth muscle cells, both thrombin and TNF
      alpha upregulated MT1-MMP expression; however, only thrombin activated MMP-2.
      Inhibition of ERK-1/2 activation blocked arterialization-induced upregulation of
      MMP-2, MMP-9, and MT1-MMP. Thus, thrombin, inflammatory mediators, and activation
      of the ERK-1/2 pathway control MMP and TIMP-2 expression in arterialized vein
      grafts.

PMID- 16284241
TI  - Endotoxin enhances microvascular thrombosis in mouse cremaster venules via a TLR4
      dependent, neutrophil-independent mechanism.
AB  - Endotoxemia promotes adhesive interactions between platelets and microvascular
      endothelium in vivo. We sought to determine whether endotoxin
      (lipopolysaccharide, LPS) modified platelet thrombus formation in mouse cremaster
      venules and whether Toll-like receptor 4 (TLR4) and neutrophils were involved in
      the response. Intravital videomicroscopy was performed in the cremaster
      microcirculation of pentobarbital-anesthetized mice; venular platelet thrombi
      were induced with a light/dye endothelial injury model. C57BL/6 mice treated with
      Escherichia coli endotoxin had enhanced rates of venular platelet thrombus
      formation: the time to microvessel occlusion was reduced by approximately 50% (P
      < 0.005) compared with saline-treated animals. Enhanced microvascular thrombosis
      was evident as early as 2 h after LPS administration. LPS had no effect on
      thrombosis in either of two mouse strains with altered TLR4 signaling
      (C57BL/10ScNJ or C3H/HeJ), whereas it enhanced thrombosis in the control strains
      (C57BL/10J and C3H/HeN). LPS also enhanced platelet adhesion to endothelium in
      the absence of light/dye injury. Platelet adhesion, but not enhanced thrombosis,
      was inhibited by depletion of circulating neutrophils. LPS failed to enhance
      platelet aggregation ex vivo and did not influence platelet P-selectin
      expression, a marker of platelet activation. These findings support the notion
      that endotoxemia promotes platelet thrombus formation independent of neutrophils
      and without enhancement of platelet aggregation, via a TLR4-dependent mechanism.

PMID- 16284242
TI  - Baroreceptor function during exercise: resetting the record.
AB  - This paper briefly reviews the historical evolution of ideas about how
      baroreflexes operate and continue to regulate arterial blood pressure during
      exercise. Observations from studies conducted in conscious humans and animals are
      emphasized and three main questions are asked. First, do baroreflexes contribute
      to arterial blood pressure regulation during exercise? Second, if baroreflexes
      contribute to blood pressure regulation during exercise, how do they do it?
      Third, are there any pathophysiological conditions in which manipulation of
      baroreflexes or baroreflex 'dysfunction' might alter exercise responses? In this
      context, ideas related to baroreflex resetting during exercise are emphasized,
      and the potential improvement in exercise tolerance in cardiovascular disease
      that might be achieved by electrical stimulation of the carotid sinus nerve is
      highlighted. Additionally, the key contributions of John Shepherd and the late
      David Donald (along with their colleagues) on related issues are noted.

PMID- 16284243
TI  - The first british reference to a case of occupational disease?

PMID- 16284244
TI  - A schizophrenia-related sensorimotor deficit links alpha 3-containing GABAA
      receptors to a dopamine hyperfunction.
AB  - Overactivity of the dopaminergic system in the brain is considered to be a
      contributing factor to the development and symptomatology of schizophrenia.
      Therefore, the GABAergic control of dopamine functions was assessed by disrupting
      the gene encoding the alpha3 subunit of the GABA(A) receptor. alpha3 knockout
      (alpha3KO) mice exhibited neither an obvious developmental defect nor apparent
      morphological brain abnormalities, and there was no evidence for compensatory up
      regulation of other major GABA(A)-receptor subunits. Anxiety-related behavior in
      the elevated-plus-maze test was undisturbed, and the anxiolytic-like effect of
      diazepam, which is mediated by alpha2-containing GABA(A) receptors, was
      preserved. As a result of the loss of alpha3 GABA(A) receptors, the GABA-induced
      whole-cell current recorded from midbrain dopamine neurons was significantly
      reduced. Spontaneous locomotor activity was slightly elevated in alpha3KO mice.
      Most notably, prepulse inhibition of the acoustic startle reflex was markedly
      attenuated in the alpha3KO mice, pointing to a deficit in sensorimotor
      information processing. This deficit was completely normalized by treatment with
      the antipsychotic D2-receptor antagonist haloperidol. The amphetamine-induced
      hyperlocomotion was not altered in alpha3KO mice compared with WT mice. These
      results suggest that the absence of alpha3-subunit-containing GABA(A) receptors
      induces a hyperdopaminergic phenotype, including a severe deficit in sensorimotor
      gating, a common feature among psychiatric conditions, including schizophrenia.
      Hence, agonists acting at alpha3-containing GABA(A) receptors may constitute an
      avenue for an effective treatment of sensorimotor-gating deficits in various
      psychiatric conditions.

PMID- 16284245
TI  - Fezl regulates the differentiation and axon targeting of layer 5 subcortical
      projection neurons in cerebral cortex.
AB  - During the development of the cerebral cortex, progenitor cells produce neurons
      that migrate to laminar positions appropriate for their birth dates, adopt
      specific neuronal identities, and form appropriate local and long-distance axonal
      connections. Here, we report that forebrain embryonic zinc-finger-like protein
      (Fezl), a putative zinc-finger transcriptional repressor, is required for the
      differentiation of projection neurons in cortical layer 5. In Fezl-deficient
      mice, these neurons display molecular, morphological, and axonal targeting
      defects. The corticospinal tract was absent in Fezl(-/-) mice, corticotectal and
      pontine projections were severely reduced, and Fezl-expressing neurons formed
      aberrant axonal projections. The expression of many molecular markers for deep
      layer neurons was reduced or absent in the Fezl(-/-) cerebral cortex. Most
      strikingly, Ctip2, a transcription factor required for the formation of the
      corticospinal tract, was not expressed in the Fezl-deficient cortex. These
      results suggest that Fezl regulates the differentiation of layer 5 subcortical
      projection neurons.

PMID- 16284247
TI  - Preceramic irrigation canals in the Peruvian Andes.
AB  - One of the most important developments in the existence of human society was the
      successful shift from a subsistence economy based on foraging to one primarily
      based on food production derived from cultivated plants and domesticated animals.
      The shift to plant food production occurred in only a few independent centers
      around the world and involved a commitment to increased sedentism and social
      interaction and to permanent agricultural fields and canals. One center was Peru,
      where early civilization and food production were beginning to develop by at
      least 4,500 years ago. New archeological evidence points to 5,400- and possible
      6,700-year-old small-scale gravity canals in a circumscribed valley of the
      western Andean foothills in northern Peru that are associated with farming on low
      terrace benches at the foot of alluvial fans in areas where the canals are drawn
      from hydraulically manageable small lateral streams. This evidence reveals early
      environmental manipulation and incipient food production in an artificially
      created wet agroecosystem rather than simply the intensive harvesting or
      gardening of plants in moist natural areas. This finding is different from
      previously conceived notions, which expected early canals in lower-elevated,
      broad coastal valleys. The evidence also points to communal organization of labor
      to construct and maintain the canals and to the scheduling of daily activities
      beyond individual households. The development of early organized irrigation
      farming was combined with a hunting and gathering economy to support an increase
      in the local population size.

PMID- 16284246
TI  - T cell Ig and mucin 1 (TIM-1) is expressed on in vivo-activated T cells and
      provides a costimulatory signal for T cell activation.
AB  - Polymorphisms in TIM-1, a member of the T cell Ig and mucin (TIM) domain family,
      are associated with relative susceptibility to the development of T helper 2
      dominated immune responses such as in allergic asthma. Recent data have also
      suggested that ligation of TIM-1 can augment T cell activation. We have found
      that the TIM-1 protein is expressed on CD4(+) T cells in vivo after intranasal
      immunization. Ectopic expression of TIM-1 during T cell differentiation results
      in a significant increase in the number of cells producing IL-4 but not IFN
      gamma. Furthermore, TIM-1 expression provides a costimulatory signal that
      increases transcription from the IL-4 promoter and from isolated nuclear factor
      of activated T cells/activating protein-1 (NFAT/AP-1) elements. Finally, we
      provide evidence that TIM-1 can be phosphorylated on tyrosine and that TIM-1
      costimulation requires its cytoplasmic tail and the conserved tyrosine within
      that domain. These results constitute evidence that TIM-1 directly couples to
      phosphotyrosine-dependent intracellular signaling pathways.

PMID- 16284248
TI  - Pyramidal neurons of upper cortical layers generated by NEX-positive progenitor
      cells in the subventricular zone.
AB  - The generation of pyramidal neurons in the mammalian neocortex has been
      attributed to proliferating progenitor cells within the ventricular zone (VZ).
      Recently, the subventricular zone (SVZ) has been recognized as a possible source
      of migratory neurons in brain slice preparations, but the relevance of these
      observations for the developing neocortex in vivo remains to be defined. Here, we
      demonstrate that a subset of progenitor cells within the SVZ of the mouse
      neocortex can be molecularly defined by Cre recombinase expression under control
      of the NEX/Math2 locus, a neuronal basic helix-loop-helix gene that by itself is
      dispensable for cortical development. NEX-positive progenitors are generated by
      VZ cells, move into the SVZ, and undergo multiple asymmetrical and symmetrical
      cell divisions that produce a fraction of the neurons in the upper cortical
      layers. Our data suggest that NEX-positive progenitors within the SVZ are
      committed to a glutamatergic neuronal fate and have evolved to expand the number
      of cortical output neurons that is characteristic for the mammalian forebrain.

PMID- 16284249
TI  - Parvoviral virions deploy a capsid-tethered lipolytic enzyme to breach the
      endosomal membrane during cell entry.
AB  - Enveloped viruses deliver their virions into the host cell by fusion with the
      cellular plasma or endosomal membrane, thus creating topological continuity
      between the cytosol and the inside of the viral envelope. Nonenveloped viruses
      are, by their very nature, denied this strategy and must employ alternative
      methods to breach their host cell's delimiting membrane. We show here that the
      compact icosahedral parvoviral virion gains entry by deploying a lipolytic
      enzyme, phospholipase A(2) (PLA(2)), that is expressed at the N terminus of VP1,
      the minor coat protein. This region of VP1 is normally sequestered within the
      viral shell but is extruded during the entry process as a capsid-tethered domain.
      A single amino acid substitution in the active site of the VP1 PLA(2) inactivates
      enzymatic activity and abrogates infectivity. We have used transencapsidation of
      a vector expressing green fluorescent protein to show that infection by this
      PLA(2)-defective mutant can be complemented by coinfection with wild-type or
      mutant full virions, provided they can express a functional PLA(2). Even though
      wild-type empty capsids contain an active form of the enzyme, it is not
      externalized under physiological conditions, and such capsids are not able to
      complement the PLA(2) mutant. Significantly, highly efficient rescue can be
      achieved by polyethyleneimine-induced endosome rupture or by coinfection with
      adenovirus as long as uptake of the two viruses is simultaneous and the
      adenovirus is capable of deploying pVI, a capsid protein with endosomolytic
      activity. Together, these results demonstrate a previously unrecognized enzymatic
      mechanism for nonenveloped virus penetration.

PMID- 16284250
TI  - A structural model for unfolded proteins from residual dipolar couplings and
      small-angle x-ray scattering.
AB  - Natively unfolded proteins play key roles in normal and pathological biochemical
      processes. Despite their importance for function, this category of proteins
      remains beyond the reach of classical structural biology because of their
      inherent conformational heterogeneity. We present a description of the intrinsic
      conformational sampling of unfolded proteins based on residue-specific /Psi
      propensities from loop regions of a folded protein database and simple volume
      exclusion. This approach is used to propose a structural model of the 57-aa,
      natively disordered region of the nucleocapsid-binding domain of Sendai virus
      phosphoprotein. Structural ensembles obeying these simple rules of conformational
      sampling are used to simulate averaged residual dipolar couplings (RDCs) and
      small-angle x-ray scattering data. This protein is particularly informative
      because RDC data from the equally sized folded and unfolded domains both report
      on the unstructured region, allowing a quantitative analysis of the degree of
      order present in this part of the protein. Close agreement between experimental
      and simulated RDC and small-angle x-ray scattering data validates this simple
      model of conformational sampling, providing a precise description of local
      structure and dynamics and average dimensions of the ensemble of sampled
      structures. RDC data from two urea-unfolded systems are also closely reproduced.
      The demonstration that conformational behavior of unfolded proteins can be
      accurately predicted from the primary sequence by using a simple set of rules has
      important consequences for our understanding of the structure and dynamics of the
      unstructured state.

PMID- 16284251
TI  - Mechanism of mRNA transport in the nucleus.
AB  - The mechanism of transport of mRNA-protein (mRNP) complexes from transcription
      sites to nuclear pores has been the subject of many studies. Using molecular
      beacons to track single mRNA molecules in living cells, we have characterized the
      diffusion of mRNP complexes in the nucleus. The mRNP complexes move freely by
      Brownian diffusion at a rate that assures their dispersion throughout the nucleus
      before they exit into the cytoplasm, even when the transcription site is located
      near the nuclear periphery. The diffusion of mRNP complexes is restricted to the
      extranucleolar, interchromatin spaces. When mRNP complexes wander into dense
      chromatin, they tend to become stalled. Although the movement of mRNP complexes
      occurs without the expenditure of metabolic energy, ATP is required for the
      complexes to resume their motion after they become stalled. This finding provides
      an explanation for a number of observations in which mRNA transport appeared to
      be an enzymatically facilitated process.

PMID- 16284253
TI  - Study of single-nucleotide polymorphisms by means of electrical conductance
      measurements.
AB  - Understanding the complexities of DNA has been a hallmark of science for over a
      half century, and one of the important topics in DNA research is recognizing the
      occurrence of mutations in the base-stack. In this article, we present a study of
      SNPs by direct-contact electrical measurements to a single DNA duplex. We have
      used short, 11- and 12-bp dsDNA to investigate the change in conductance that
      occurs if a single base pair, a single base, or two separate bases in the stack
      are modified. All measurements are carried out in aqueous solution with the DNA
      chemically bound to the electrodes. These measurements demonstrate that the
      presence of a single base pair mismatch can be identified by the conductance of
      the molecule and can cause a change in the conductance of dsDNA by as much as an
      order of magnitude, depending on the specific details of the double helix and the
      single nucleotide polymorphism.

PMID- 16284252
TI  - The effect of TERC haploinsufficiency on the inheritance of telomere length.
AB  - Telomeres protect chromosome ends from end-to-end fusion and degradation. Loss of
      telomere function causes cell-cycle arrest or cell death. Autosomal dominant
      dyskeratosis congenita (AD DC), a rare inherited bone marrow failure syndrome, is
      caused by mutations in TERC, the RNA component of telomerase. Here, we studied
      the telomere dynamics over three generations in a 32-member extended family with
      AD DC due to a TERC gene deletion. Our analysis shows that peripheral blood cells
      from family members haploinsufficient for TERC have very short telomeres.
      Telomeres are equally short in all individuals carrying the TERC gene deletion
      irrespective of their age. Chromosome-specific telomere analysis distinguishing
      the parental origin of telomeres showed that in gene deletion carriers, paternal
      and maternal telomeres are similarly short and similar in length to those of the
      affected parent. In children of affected parents who have normal TERC genes,
      parental telomeres are again similar in length, but two generations appear to be
      necessary to fully restore normal telomere length. These results are consistent
      with a model in which telomerase preferentially acts on the shortest telomeres.
      When TERC is limiting, this preference leads to the accelerated shortening of
      longer telomeres. The limited amount of active telomerase in TERC RNA
      haploinsufficiency may not be able to maintain the minimal length of the
      increasing number of short telomeres. Thus, the number of cells with excessively
      short telomeres and the degree of residual telomerase activity may determine the
      onset of disease in patients with AD DC.

PMID- 16284254
TI  - Regulation of endothelial nitric oxide synthase by small RNA.
AB  - Repeats (27-nt) in intron 4 have been shown to play a cis-acting role in
      endothelial nitric oxide synthase (eNOS) promoter activity. We hypothesize that
      the 27-nt repeats could be the source of small nuclear RNA specifically
      regulating eNOS expression. In this study, we used synthesized 27-nt RNA duplex
      and found that the eNOS gene transcriptional efficiency was reduced 63% (0.047 +/
      0.009 vs. 0.126 +/- 0.015, P < 0.01) by nuclear run-on assay. In endothelial
      cells transfected with the 27-nt small RNA duplex, we found that the eNOS mRNA
      and protein levels were decreased by >64% (P < 0.01). Conversely, a randomly
      selected 27-nt from luciferase gene had no effect on the eNOS expression.
      Furthermore, this eNOS silencing effect appeared to be reversible under the
      stimulation of vascular endothelial growth factor (10 ng/ml), which is known to
      up-regulate eNOS expression. Using in situ hybridization and Northern blotting,
      we observed the presence of endogenous eNOS intron 4-derived 27-nt small RNA,
      which was confined to the nucleus. In summary, we demonstrated that intron-based
      microRNAs in eNOS can induce significant gene specific transcriptional
      suppression, which could be an effective negative feedback regulator for gene
      expression.

PMID- 16284255
TI  - Newborns' preference for face-relevant stimuli: effects of contrast polarity.
AB  - There is currently no agreement as to how specific or general are the mechanisms
      underlying newborns' face preferences. We address this issue by manipulating the
      contrast polarity of schematic and naturalistic face-related images and assessing
      the preferences of newborns. We find that for both schematic and naturalistic
      face images, the contrast polarity is important. Newborns did not show a
      preference for an upright face-related image unless it was composed of darker
      areas around the eyes and mouth. This result is consistent with either
      sensitivity to the shadowed areas of a face with overhead (natural) illumination
      and/or to the detection of eye contact.

PMID- 16284256
TI  - Identification of a recurrent breakpoint within the SHANK3 gene in the 22q13.3
      deletion syndrome.
AB  - INTRODUCTION: The 22q13.3 deletion syndrome (MIM 606232) is characterised by
      neonatal hypotonia, normal to accelerated growth, absent to severely delayed
      speech, global developmental delay, and minor dysmorphic facial features. We
      report the molecular characterisation of the deletion breakpoint in two unrelated
      chromosome 22q13.3 deletion cases. METHODS: The deletions were characterised by
      FISH, checked for other abnormalities by array-CGH, and confirmed by Real-Time
      PCR, and finally the breakpoints were cloned, sequenced, and compared. RESULTS:
      Both cases show the cardinal features of the 22q13.3 deletion syndrome associated
      with a deletion involving the last 100 kb of chromosome 22q13.3. The cases show a
      breakpoint within the same 15 bp repeat unit, overlapping the results obtained by
      Wong and colleagues in 1997 and suggesting that a recurrent deletion breakpoint
      exists within the SHANK3 gene. The direct repeat involved in these 22q13 deletion
      cases is presumably able to form slipped (hairpin) structures, but it also has a
      strong potential for forming tetraplex structures. DISCUSSION: Three cases with a
      common breakpoint within SHANK3 share a number of common phenotypic features,
      such as mental retardation and developmental delay with severely delayed or
      absent expressive speech. The two cases presented here, having a deletion
      partially overlapping the commercial subtelomeric probe, highlight the
      difficulties in interpreting FISH results and suggest that many similar cases may
      be overlooked.

PMID- 16284258
TI  - Determination of the interfacial water content in protein-protein complexes from
      free energy simulations.
AB  - The question as to how many tightly or weakly bound water molecules are located
      in interfaces between protein-protein complex constituents is addressed from a
      phase equilibrium point of view by developing a theory in the canonical ensemble.
      A fast method based on free energy simulations is described for computing the
      number of water molecules in the interface regions. Results are given for 211
      interfacial cavities of 26 antigen-antibody complexes for which experimentally
      determined structures are found in the Protein Data Bank. The accuracy of the
      method is assessed and the computational water content is compared with
      experimental data, revealing the amount of water molecules not resolved by
      experimental approaches.

PMID- 16284257
TI  - Influence of chain length and unsaturation on sphingomyelin bilayers.
AB  - Sphingomyelins (SMs) are among the most common phospholipid components of plasma
      membranes, usually constituting a mixture of several molecular species with
      various fatty acyl chain moieties. In this work, we utilize atomistic molecular
      dynamics simulations to study the differences in structural and dynamical
      properties of bilayers comprised of the most common natural SM species. Keeping
      the sphingosine moiety unchanged, we vary the amide bonded acyl chain from 16 to
      24 carbons in length and examine the effect of unsaturation by comparing lipids
      with saturated and monounsaturated chains. As for structural properties, we find
      a slight decrease in average area per lipid and a clear linear increase in
      bilayer thickness with increasing acyl chain length both in saturated and
      unsaturated systems. Increasing the acyl chain length is found to further the
      interdigitation across the bilayer center. This is related to the dynamics of SM
      molecules, as the lateral diffusion rates decrease slightly for an increasing
      acyl chain length. Interdigitation also plays a role in interleaflet friction,
      which is stronger for unsaturated chains. The effect of the cis double bond is
      most significant on the local order parameters and rotation rates of the chains,
      though unsaturation shows global effects on overall lipid packing and dynamics as
      well. Regarding hydrogen bonding or properties related to the lipid/water
      interface region, no significant effects were observed due to varying chain
      length or unsaturation. The significance of the findings presented is discussed.

PMID- 16284259
TI  - Structure and lipid interaction of N-palmitoylsphingomyelin in bilayer membranes
      as revealed by 2H-NMR spectroscopy.
AB  - Selectively deuterated N-palmitoyl sphingomyelins were studied by deuterium
      nuclear magnetic resonance spectroscopy ((2)H-NMR) to elucidate the backbone
      conformation as well as the interaction of the sphingolipids with
      glycerophospholipids. Macroscopic alignment of the lipid bilayers provided good
      spectral resolution and permitted the convenient control of bilayer hydration.
      Selective deuteration at the acyl chain carbons C(2) and C(3) revealed that the N
      acyl chain performs a bend, similar to the sn-2 chain of the
      phosphatidylcholines. Profiles of C-D bond order parameters were derived from the
      segmental quadrupolar splittings for sphingomyelin alone and for sphingomyelin
      phosphatidycholine mixtures. In the liquid-crystalline state, the N-acyl chain of
      sphingomyelin alone revealed significantly more configurational order than the
      chains of homologous disaturated or monounsaturated phosphatidylcholines. The
      average chain order parameters and the relative width of the order parameter
      distribution were correlated over a range of bilayer compositions. The
      temperature dependence of the (2)H-NMR spectra revealed phase separation in
      bilayers composed of sphingomyelin and monounsaturated phosphatidylcholine, in
      broad agreement with existing phase diagrams.

PMID- 16284260
TI  - Change in rigidity in the activated form of the glucose/galactose receptor from
      Escherichia coli: a phenomenon that will be key to the development of biosensors.
AB  - Recently a periplasmic glucose/galactose binding protein, GGRQ26C, immobilized on
      a gold surface has been used as an active part of a glucose biosensor based on
      quartz microbalance technique. However the nature of the glucose detection was
      not clear. Here we have found that the receptor protein film immobilized on the
      gold surface increases its rigidity when glucose is added, which explains the
      unexpected detection signal. To study the rigidity change, we developed a new
      fast and simple method based on using atomic force microscopy (AFM) in tapping
      mode. The method was verified by explicit measurements of the Young's modulus of
      the protein film by conventional AFM methods. Since there are a host of receptors
      that undergo structural change when activated by ligand, AFM can play a key role
      in the development and/or optimization of biosensors based on rigidity changes in
      biomolecules.

PMID- 16284262
TI  - Simulations of (an)isotropic diffusion on curved biological surfaces.
AB  - We present a computational particle method for the simulation of isotropic and
      anisotropic diffusion on curved biological surfaces that have been reconstructed
      from image data. The method is capable of handling surfaces of high curvature and
      complex shape, which are often encountered in biology. The method is validated on
      simple benchmark problems and is shown to be second-order accurate in space and
      time and of high parallel efficiency. It is applied to simulations of diffusion
      on the membrane of endoplasmic reticula (ER) in live cells. Diffusion simulations
      are conducted on geometries reconstructed from real ER samples and are compared
      to fluorescence recovery after photobleaching experiments in the same ER samples
      using the transmembrane protein tsO45-VSV-G, C-terminally tagged with green
      fluorescent protein. Such comparisons allow derivation of geometry-corrected
      molecular diffusion constants for membrane components from fluorescence recovery
      after photobleaching data. The results of the simulations indicate that the
      diffusion behavior of molecules in the ER membrane differs significantly from the
      volumetric diffusion of soluble molecules in the lumen of the same ER. The
      apparent speed of recovery differs by a factor of approximately 4, even when the
      molecular diffusion constants of the two molecules are identical. In addition,
      the specific shape of the membrane affects the recovery half-time, which is found
      to vary by a factor of approximately 2 in different ER samples.

PMID- 16284261
TI  - Stochastic regulation in early immune response.
AB  - Living cells may be considered noisy or stochastic biochemical reactors. In
      eukaryotic cells, in which the number of protein or mRNA molecules is relatively
      large, the stochastic effects originate primarily in regulation of gene activity.
      Transcriptional activity of a gene can be initiated by transactivator molecules
      binding to the specific regulatory site(s) in the target gene. The stochasticity
      of activator binding and dissociation is amplified by transcription and
      translation, since target gene activation results in a burst of mRNAs molecules,
      and each copy of mRNA then serves as a template for numerous protein molecules.
      In this article, we reformulate our model of the NF-kappaB regulatory module to
      analyze a single cell regulation. Ordinary differential equations, used for
      description of fast reaction channels of processes involving a large number of
      molecules, are combined with a stochastic switch to account for the activity of
      the genes involved. The stochasticity in gene transcription causes simulated
      cells to exhibit large variability. Moreover, none of them behaves like an
      average cell. Although the average mRNA and protein levels remain constant before
      tumor necrosis factor (TNF) stimulation, and stabilize after a prolonged TNF
      stimulation, in any single cell these levels oscillate stochastically in the
      absence of TNF and keep oscillating under the prolonged TNF stimulation. However,
      in a short period of approximately 90 min, most cells are synchronized by the TNF
      signal, and exhibit similar kinetics. We hypothesize that this synchronization is
      crucial for proper activation of early genes controlling inflammation. Our
      theoretical predictions of single cell kinetics are supported by recent
      experimental studies of oscillations in NF-kappaB signaling made on single cells.

PMID- 16284263
TI  - Transition in the temperature-dependence of GFP fluorescence: from proton wires
      to proton exit.
AB  - In green fluorescent protein, photo-excitation leads to excited-state proton
      transfer from its chromophore, leaving behind a strongly fluorescing anion, while
      the proton is commonly thought to migrate internally to Glu-222. X-ray data show
      that the protein contains more extended hydrogen-bonded networks that can support
      proton migration (i.e., proton wires). Here we study the temperature-dependence
      of the transient fluorescence from both the acid and anionic forms up to 15 ns.
      At low temperatures, we find that the (lifetime-corrected) fluorescence of the
      acidic form decays asymptotically as t(-1/2), following quantitatively the
      solution of a one-dimensional diffusion equation for reversible geminate
      recombination with quenching. This indicates proton migration along the internal
      proton wires. A small degree of geminate proton quenching is attributed to the
      formation of the zwitterion by proton migration on a side-branch of the proton
      wire. Above 230 K, the fluorescence kinetics undergo a transition, exhibiting an
      asymptotic t(-3/2) decay, and the quenching effect disappears. We interpret these
      findings as evidence for a conformational change enabling the rotation of Thr
      203, which eventually allows the proton to escape to the exterior solution.

PMID- 16284264
TI  - Chemical and structural disorder in eumelanins: a possible explanation for
      broadband absorbance.
AB  - We report the results of an experimental and theoretical study of the electronic
      and structural properties of a key eumelanin precursor-5,6,-dihydroxyindole-2
      carboxylic acid (DHICA)-and its dimeric forms. We have used optical spectroscopy
      to follow the oxidative polymerization of DHICA to eumelanin and observe red
      shifting and broadening of the absorption spectrum as the reaction proceeds.
      First principles density functional theory calculations indicate that DHICA
      oligomers (possible reaction products of oxidative polymerization) have the gap
      between the highest occupied molecular orbital and the lowest unoccupied
      molecular orbital red-shifted gaps with respect to the monomer. Furthermore,
      different bonding configurations (leading to oligomers with different structures)
      produce a range of gaps. These experimental and theoretical results lend support
      to the chemical disorder model where the broadband monotonic absorption
      characteristic of all melanins is a consequence of the superposition of a large
      number of nonhomogeneously broadened Gaussian transitions associated with each of
      the components of a melanin ensemble. These results suggest that the traditional
      model of eumelanin as an amorphous organic semiconductor is not required to
      explain its optical properties and should be thoroughly reexamined. These results
      have significant implications for our understanding of the physics, chemistry,
      and biological function of these important biological macromolecules. Indeed, one
      may speculate that the robust functionality of melanins in vitro is a direct
      consequence of its heterogeneity, i.e., chemical disorder is a "low cost" natural
      resource in these systems.

PMID- 16284266
TI  - Detergent-resistant, ceramide-enriched domains in sphingomyelin/ceramide
      bilayers.
AB  - When cell membranes are treated with Triton X-100 or other detergents at 4
      degrees C, a nonsolubilized fraction can often be recovered, the "detergent
      resistant membranes", that is not found when detergent treatment takes place at
      37 degrees C. Detergent-resistant membranes may be related in some cases to
      membrane "rafts". However, several basic aspects of the formation of detergent
      resistant membranes are poorly understood. To answer some of the relevant
      questions, a simple bilayer composition that would mimic detergent-resistant
      membranes was required. The screening of multiple lipid compositions has shown
      that the binary mixture egg sphingomyelin/egg ceramide (SM/Cer) exhibits the
      required detergent resistance. In detergent-free membranes composed of different
      mixtures of SM and Cer (5-30 mol % of Cer) differential scanning calorimetry,
      fluorescence spectroscopy, and fluorescence microscopy experiments reveal the
      presence of discrete, Cer-enriched gel domains in a broad temperature range. In
      particular, at temperatures below SM phase transition ( approximately 40 degrees
      C) two gel (respectively Cer-rich and SM-rich) phases are directly observed using
      fluorescence microscopy. Although pure SM membranes are fully solubilized by
      Triton X-100 at room temperature, 5 mol % Cer is also enough to induce detergent
      resistance, even with a large detergent excess and lengthy equilibration times.
      Short-chain Cers do not give rise to detergent resistance. SM/Cer mixtures
      containing up to 30 mol % Cer become fully soluble at approximately 50 degrees C,
      i.e., well above the gel-fluid transition temperature of SM. The combined results
      of temperature-dependent solubilization and differential scanning calorimetry
      reveal that SM-rich domains are preferentially solubilized over the Cer-rich ones
      as soon as the former melt (i.e., at approximately 40 degrees C). As a
      consequence, at temperatures allowing only partial solubilization, the
      nonsolubilized residue is enriched in Cer with respect to the original bilayer
      composition. Fluorescence microscopy of giant unilamellar vesicles at room
      temperature clearly shows that SM-rich domains are preferentially solubilized
      over the Cer-rich ones and that the latter become more rigid and extensive as a
      consequence of the detergent effects. These observations may be relevant to the
      phenomena of sphingomyelinase-dependent signaling, generation of "raft
      platforms", and detergent-resistant cell membranes.

PMID- 16284265
TI  - An energy-efficient gating mechanism in the acetylcholine receptor channel
      suggested by molecular and Brownian dynamics.
AB  - Acetylcholine receptors mediate electrical signaling between nerve and muscle by
      opening and closing a transmembrane ion conductive pore. Molecular and Brownian
      dynamics simulations are used to shed light on the location and mechanism of the
      channel gate. Four separate 5 ns molecular dynamics simulations are carried out
      on the imaged structure of the channel, a hypothetical open structure with a
      slightly wider pore and a mutant structure in which a central ring of hydrophobic
      residues is replaced by polar groups. Water is found to partially evacuate the
      pore during molecular simulations of the imaged structure, whereas ions face a
      large energy barrier and do not conduct through the channel in Brownian dynamics
      simulations. The pore appears to be in a closed configuration despite containing
      an unobstructed pathway across the membrane as a series of hydrophobic residues
      in the center of the channel provide an unfavorable home to water and ions. When
      the channel is widened slightly, water floods into the channel and ions conduct
      at a rate comparable to the currents measured experimentally in open channels.
      The pore remains permeable to ions provided the extracellular end of the pore
      lining helix is restrained near the putative open configuration to mimic the
      presence of the ligand binding domain. Replacing some of the hydrophobic residues
      with polar ones decreases the barrier for ion permeation but does not result in
      significant currents. The channel is posited to utilize an energy efficient
      gating mechanism in which only minor conformational changes of the hydrophobic
      region of the pore are required to create macroscopic changes in conductance.

PMID- 16284267
TI  - A competitive kinetic model of nucleic acid surface hybridization in the presence
      of point mutants.
AB  - Microarray analysis has become increasingly complex due to the growing size of
      arrays and the inherent cross-binding of targets. In this work, we explore the
      effects of matched and mismatched target species concentrations, temperature, and
      the time of hybridization on sensing specificity in two-component systems. A
      finite element software is used to simulate the diffusion of DNA through a
      microfluidic chamber to the sensing surface where hybridization of DNA is modeled
      using the corresponding kinetic equation. Comparison between a single-component
      system, where only one target is allowed to bind to a specific zone, and a two
      component system, where more than one target can hybridize in a sensing zone,
      uncovers significant kinetic disparities during the transitory state; however, at
      thermodynamic equilibrium a modified Langmuir isotherm governs the bound amount
      of both species. The results presented suggest that it may be more appropriate to
      consider collective rather than quasi-independent interaction of targets in
      multicomponent systems.

PMID- 16284268
TI  - Aqueous diffusion pathways as a part of the ventricular cell ultrastructure.
AB  - The physical organization of the ventricular myocyte includes barriers for the
      movement of objects of varying dimensions ranging from ions to solid particles.
      There are two kinds of diffusion in the cell: lateral (in membranes) and aqueous.
      Here we examine the size constraints of aqueous diffusion pathways and discuss
      their impact on cellular physiology. Calibrated gold nanoparticles were used to
      probe the accessibility of the entire transverse-axial tubular system (TATS), the
      sarcoplasm, and intracellular structures. The TATS tubules, although up to 300 nm
      in diameter, permitted only particles </=11 nm to enter. When calibrated
      nanoparticles were added to permeabilized ventricular cells, particles </=11 nm
      were found in the sarcoplasm. The distribution of nanoparticles in the cells
      allowed us to conclude that 1), the TATS and the sarcoplasm are accessible only
      for particles </=11 nm; 2), the gaps between T-tubules and junctional
      sarcoplasmic reticulum (jSR), jSR and mitochondria, and intermitochondrial
      contacts are inaccessible for particles with physical size >3 nm; 3), the
      mitochondrial voltage-dependent anion channel and the nuclear pore complex in
      ventricular cells could not be penetrated by particles >/=6 nm; and 4), there is
      a difference in size clearance between transversal and longitudinal sarcoplasmic
      diffusional pathways.

PMID- 16284269
TI  - Calculation of absolute protein-ligand binding affinity using path and endpoint
      approaches.
AB  - A comparative analysis is provided of rigorous and approximate methods for
      calculating absolute binding affinities of two protein-ligand complexes: the FKBP
      protein bound with small molecules 4-hydroxy-2-butanone and FK506. Our rigorous
      approach is an umbrella sampling technique where a potential of mean force is
      determined by pulling the ligand out of the protein active site over several
      simulation windows. The results of this approach agree well with experimentally
      observed binding affinities. Also assessed is a commonly used approximate
      endpoint approach, which separately estimates enthalpy, solvation free energy,
      and entropy. We show that this endpoint approach has numerous variations, all of
      which are prone to critical shortcomings. For example, conventional harmonic and
      quasiharmonic entropy estimation procedures produce disparate results for the
      relatively simple protein-ligand systems studied in this work.

PMID- 16284270
TI  - The electromechanics of DNA in a synthetic nanopore.
AB  - We have explored the electromechanical properties of DNA on a nanometer-length
      scale using an electric field to force single molecules through synthetic
      nanopores in ultrathin silicon nitride membranes. At low electric fields, E < 200
      mV/10 nm, we observed that single-stranded DNA can permeate pores with a diameter
      >/=1.0 nm, whereas double-stranded DNA only permeates pores with a diameter >/=3
      nm. For pores <3.0 nm diameter, we find a threshold for permeation of double
      stranded DNA that depends on the electric field and pH. For a 2 nm diameter pore,
      the electric field threshold is approximately 3.1 V/10 nm at pH = 8.5; the
      threshold decreases as pH becomes more acidic or the diameter increases.
      Molecular dynamics indicates that the field threshold originates from a
      stretching transition in DNA that occurs under the force gradient in a nanopore.
      Lowering pH destabilizes the double helix, facilitating DNA translocation at
      lower fields.

PMID- 16284271
TI  - Protective effect of vitamin C against double-strand breaks in reconstituted
      chromatin visualized by single-molecule observation.
AB  - Direct attack to genomic DNA by reactive oxygen species causes various types of
      lesions, including base modifications and strand breaks. The most significant
      lesion is considered to be an unrepaired double-strand break that can lead to
      fatal cell damage. We directly observed double-strand breaks of DNA in
      reconstituted chromatin stained by a fluorescent cyanine dye, YOYO (quinolinium,
      1,1'-[1,3- propanediylbis[(dimethyliminio)-3,1- propanediyl]]bis[4-[(3-methyl
      2(3H)-benzoxazolylidene)methyl]]-, tetraiodide), in solution, where YOYO is known
      to have the ability to photo-cleave DNAs by generating reactive oxygen species.
      Reconstituted chromatin was assembled from large circular DNA (106 kbp) with core
      histone proteins. We also investigated the effect of vitamin C (ascorbic acid) on
      preventing photo-induced double-strand breaks in a quantitative manner. We found
      that DNA is protected against double-strand breaks by the addition of ascorbic
      acid, and this protective effect is dose dependent. The effective kinetic
      constant of the breakage reaction in the presence of 5 mM ascorbic acid is 20
      times lower than that in the absence of ascorbic acid. This protective effect of
      ascorbic acid in reconstituted chromatin is discussed in relation to the highly
      compacted polynucleosomal structure. The results highlight the fact that single
      molecule observation is a useful tool for studying double-strand breaks in giant
      DNA and chromatin.

PMID- 16284272
TI  - Optical readout of gold nanoparticle-based DNA microarrays without silver
      enhancement.
AB  - We present a novel readout scheme for gold nanoparticle-based DNA microarrays
      relying on "Laser-Induced Scattering around a NanoAbsorber". It provides direct
      counting of individual nanoparticles present on each array spot and stable
      signals, without any silver enhancement. Given the detection of nanometer-sized
      particles, which minimize the steric hindrance, the linear dynamic range of the
      method is particularly large and well suited for microarray detection.

PMID- 16284273
TI  - Melanosomes transported by myosin-V in Xenopus melanophores perform slow 35 nm
      steps.
AB  - We studied the motion of pigment organelles driven by myosin-V in Xenopus
      melanophores using a tracking technique with precision of 2 nm. The organelle
      trajectories showed occasional steps with a distribution centered at 35 nm and a
      standard deviation of 13 nm, in agreement with the step size of myosin-V
      determined in vitro. In contrast, trajectories of melanosomes in cells expressing
      a dominant negative form of myosin-V did not show steps. The step duration was in
      the range 20-80 ms, slower than what it would be expected from in vitro results.
      We speculate that the cytoplasm high viscosity may affect significantly the
      melanosomes' motion.

PMID- 16284274
TI  - Mechanics of enveloped virus entry into host cells.
AB  - Enveloped viruses such as HIV-1 enter their hosts by first establishing a contact
      region at the cell surface, which is stabilized by the formation of receptor
      ligand complexes. We show that the favorable contact energy stemming from the
      formation of the receptor complexes in the interaction zone is sufficient to
      drive the engulfment of the virus by the cell. Using a continuum model, we show
      that the equilibrium engulfment depth and the force driving the engulfment are
      functions of the virus size and the complex formation energy. Resistance to
      engulfment is dominated by the elastic deformation of the cytoskeleton.

PMID- 16284275
TI  - A simple theoretical model explains dynein's response to load.
AB  - Recent experiment showed that cytoplasmic dynein 1, a molecular motor responsible
      for cargo transport in cells, functions as a gear in response to external load.
      In the presence of vanishing or small external load, dynein walks with 24- or 32
      nm steps, whereas at high external load, its step size is reduced to 8 nm. A
      simple model is proposed to account for this property of dynein. The model
      assumes that the chemical energy of ATP hydrolysis is used through a loose
      coupling between the chemical reaction and the translocation of dynein along
      microtubule. This loose chemomechanical coupling is represented by the loosely
      coupled motions of dynein along two different reaction coordinates. The first
      reaction coordinate is tightly coupled to the chemical reaction and describes the
      protein conformational changes that control the chemical processes, including ATP
      binding and hydrolysis, and ADP-Pi release. The second coordinate describes the
      translocation of dynein along microtubule, which is directly subject to the
      influence of the external load. The model is used to explain the experimental
      data on the external force dependence of the dynein step size as well as the ATP
      concentration dependence of the stall force. A number of predictions, such as the
      external force dependence of speed of translocation, ATP hydrolysis rate, and
      dynein step sizes, are made based on this theoretical model. This model provides
      a simple understanding on how a variable chemomechanical coupling ratio can be
      achieved and used to optimize the biological function of dynein.

PMID- 16284276
TI  - TrkAd5: A novel therapeutic agent for treatment of inflammatory pain and asthma.
AB  - Elevated levels of nerve growth factor have been linked to the onset and
      persistence of many pain-related disorders and asthma. Described here are the
      design, expression, refolding, and purification of a monomeric (nonstrand
      swapped) form of the binding domain of the nerve growth factor receptor,
      designated TrkAd5. We have shown that TrkAd5 produced recombinantly binds nerve
      growth factor with picomolar affinity. TrkAd5 has been characterized using a
      variety of biophysical and biochemical assays and is shown here to be stable in
      both plasma and urine. The palliative effects of TrkAd5 are demonstrated in
      animal models of inflammatory pain and allergic asthma. We conclude that TrkAd5
      will prove effective in ameliorating both acute and chronic conditions where
      nerve growth factor acts as a mediator and suggest a role for its application in
      vivo as a novel therapeutic.

PMID- 16284277
TI  - Cumulative activation of akt and consequent inhibition of glycogen synthase
      kinase-3 by brain-derived neurotrophic factor and insulin-like growth factor-1 in
      cultured hippocampal neurons.
AB  - Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1)
      seem to play key roles in mediating neuronal plasticity in the hippocampus. In
      the current studies, we have used cultured hippocampal neurons to study possible
      interactions between the two growth factors in modulating neuronal signaling
      pathways. BDNF and IGF-1 were found to each effectively activate the
      neuroprotective Akt pathway, with the magnitude of activation being at least
      additive when cultures were simultaneously treated with supramaximal
      concentrations of peptides. Likewise, a cumulative inhibitory Akt-dependent
      phosphorylation of proapoptotic glycogen synthase kinase-3 was observed.
      Immunofluorescent studies demonstrated that a single population of neurons
      responded to BDNF and IGF-1. In contrast, the magnitude of BDNF-stimulated
      extracellular signal-regulated kinase (ERK) activation was found to be much
      greater than that of IGF-1-stimulated ERK, such that the difference in magnitude
      stimulated by BDNF in the presence and absence of IGF-1 did not reach statistical
      significance. Consistent with the observed agonist-stimulated activation of Akt,
      BDNF and IGF-1 were both found to act as neurotrophins, enhancing neuronal
      survival under low-insulin culture conditions. Maximal survival was achieved when
      both growth factors were present. These findings provide insight into the
      significance of multiple growth factors stimulating activation of ERK and Akt in
      the central nervous system. In some cases, the magnitude of activation required
      to elicit biological responses may be achieved only with a combination of
      compounds.

PMID- 16284278
TI  - Fibrin affinity of erythrocyte-coupled tissue-type plasminogen activators endures
      hemodynamic forces and enhances fibrinolysis in vivo.
AB  - Plasminogen activators (PAs; e.g., tissue-type, tPA) coupled to red blood cells
      (RBCs) display in vivo features useful for thromboprophylaxis: prolonged
      circulation, minimal extravasation, and preferential lysis of nascent versus
      preexisting clots. Yet, factors controlling the activity of RBC-bound PAs in vivo
      are not defined and may not mirror the profile of soluble PAs. We tested the role
      of RBC/PA binding to fibrin in fibrinolysis. RBC/tPA and RBC/tPA variant with low
      fibrin affinity (rPA) bound to and lysed plasminogen-containing fibrin clots in
      vitro comparably. In contrast, when coinjected in mice with fibrin emboli lodging
      in pulmonary vasculature, only RBC/tPA accumulated in lungs, which resulted in a
      more extensive fibrinolysis versus RBC/rPA (p < 0.01). Reconciling this apparent
      divergence between in vitro and in vivo behaviors, RBC/tPA, but not RBC/rPA
      perfused over fibrin in vitro at physiological shear stress bound to fibrin clots
      and caused greater fibrinolysis versus RBC/rPA (p < 0.001). These results
      indicate that because of high fibrin affinity, RBC/tPA binding to clots endures
      hemodynamic stress, which enhances fibrinolysis. Behavior of RBC/PAs under
      hemodynamic pressure is an important predictor of their performance in vivo.

PMID- 16284279
TI  - Elevation of endocannabinoid levels in the ventrolateral periaqueductal grey
      through inhibition of fatty acid amide hydrolase affects descending nociceptive
      pathways via both cannabinoid receptor type 1 and transient receptor potential
      vanilloid type-1 receptors.
AB  - In the ventrolateral periaqueductal gray (PAG), activation of excitatory output
      neurons projecting monosynaptically to OFF cells in the rostral ventromedial
      medulla (RVM) causes antinociceptive responses and is under the control of
      cannabinoid receptor type-1 (CB1) and vanilloid transient receptor potential
      vanilloid type 1 (TRPV1) receptors. We studied in healthy rats the effect of
      elevation of PAG endocannabinoid [anandamide and 2-arachidonoylglycerol (2-AG)]
      levels produced by intra-PAG injections of the inhibitor of fatty acid amide
      hydrolase URB597 [cyclohexylcarbamic acid-3'-carbamoyl-biphenyl-3-yl ester] on 1)
      nociception in the "plantar test" and 2) spontaneous and tail-flick-related
      activities of RVM neurons. Depending on the dose or time elapsed since
      administration, URB597 (0.5-2.5 nmol/rat) either suppressed or increased thermal
      nociception via TRPV1 or CB1 receptors, respectively. TRPV1 or cannabinoid
      receptor agonists capsaicin (6 nmol) and (R)-(+)-[2,3-dihydro-5-methyl-3-(4
      morpholinylmethyl)pyrrolo[1,2,3,-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone
      mesylate [WIN55,212-2 (4 nmol)] also suppressed or enhanced nociception,
      respectively. URB597 dose dependently enhanced PAG anandamide and 2-AG levels,
      with probable subsequent activation of TRPV1/CB1 receptors and only CB1
      receptors, respectively. The TRPV1-mediated antinociception and CB1-mediated
      nociception caused by URB597 correlated with enhanced or reduced activity of RVM
      OFF cells, suggesting that these effects occur via stimulation or inhibition of
      excitatory PAG output neurons, respectively. Accordingly, several ventrolateral
      PAG neurons were found by immunohistochemistry to coexpress TRPV1 and CB1
      receptors. Finally, at the highest doses tested, URB597 (4 nmol/rat) and, as
      previously reported, WIN55,212-2 (25-100 nmol) also caused CB(1)-mediated
      analgesia, correlating with stimulation (possibly disinhibition) of RVM OFF
      cells. Thus, endocannabinoids affect the descending pathways of pain control by
      acting at either CB1 or TRPV1 receptors in healthy rats.

PMID- 16284280
TI  - How Gut handles your manuscript.

PMID- 16284281
TI  - An unusual cause of diarrhoea.

PMID- 16284282
TI  - Capsule pH monitoring: is wireless more?

PMID- 16284283
TI  - The role of eosinophils in inflammatory bowel disease.

PMID- 16284285
TI  - Painful gastrointestinal haemorrhage: diagnostic value of 16 detector multislice
      computed tomography.

PMID- 16284284
TI  - Molecular basis for subdividing hereditary colon cancer?

PMID- 16284286
TI  - Tumour matrilysin expression predicts metastatic potential of stage I (pT1) colon
      and rectal cancers.
AB  - BACKGROUND AND AIMS: Nodal metastases are indisputable determinants of prognosis
      for colon and rectal cancer. Using classical histological criteria, many attempts
      to predict nodal metastasis have failed, preventing the adequate management of
      stage I (pT1) cancer. We investigated the role of tumour matrilysin in predicting
      metastatic potential, and discuss its potential use in individualising treatment
      of pT1 colon and rectal cancer. METHODS: The gene signature associated with nodal
      metastasis was investigated by cDNA array in 24 colon and rectal cancers. We
      studied 494 colon and rectal cancer patients to identify risk factors for nodal
      metastasis and evaluated the potential to predict nodal metastasis by either the
      logistic regression model or the Bayesian neural network model with built-in
      matrilysin. We then inferred possible causality of nodal metastasis from
      structural equation modelling. RESULTS: cDNA array revealed that matrilysin was
      maximally upregulated in the metastasis signature identified. Tumour matrilysin
      expression emerged as a stage independent risk factor for nodal metastasis,
      resulting in a similar predictive performance in receiver operating
      characteristic curve analysis in the two models. A Bayesian approach called
      automatic relevance determination identified matrilysin as one of the most
      relevant predictors examined. Structural equation modelling suggested possible
      direct causality between matrilysin and nodal metastasis. CONCLUSIONS: We have
      provided evidence that tumour matrilysin expression is a promising biomarker
      predicting nodal metastasis of colon and rectal cancer. Analysis of tumour
      matrilysin expression would help clinicians achieve the goal of individualised
      cancer treatment based on the metastatic potential of pT1 colon and rectal
      cancer.

PMID- 16284287
TI  - Anti-monocyte chemoattractant protein 1 gene therapy attenuates experimental
      chronic pancreatitis induced by dibutyltin dichloride in rats.
AB  - BACKGROUND: Monocyte chemoattractant protein 1 (MCP-1) is a member of the C-C
      chemokine family and exerts strong chemoattractant activity in monocytes,
      macrophages, and lymphocytes. Rat pancreatic fibrosis induced by dibutyltin
      dichloride (DBTC) is considered to be an appropriate chronic pancreatitis model
      histologically and enzymatically, as has demonstrated in a previous study. AIM:
      We examined the effect of human dominant negative inhibitor of MCP-1 (mutant MCP
      1) on progression of chronic pancreatitis induced by DBTC in a rat model.
      METHODS: We used the experimental model of chronic pancreatitis induced by DBTC
      in rats. Mutant MCP-1 or empty plasmid at a dose of 50 microg/body weight was
      administrated into rat thigh muscles on days 4, 11, and 18 after administration
      of DBTC. On days 14 and 28, we evaluated the effect of mutant MCP-1
      morphologically and biochemically. RESULTS: The mutant MCP-1 treated group
      inhibited early pancreatic inflammation and later pancreatic fibrosis
      histologically, and showed a decrease in serum MCP-1 concentration,
      intrapancreatic hydroxyproline, alpha-smooth muscle actin, and an increase in
      intrapancreatic amylase and protein content compared with the empty plasmid
      treated group. The mutant MCP-1 group also inhibited intrapancreatic mRNA
      expression of cytokines and chemokines. CONCLUSIONS: : Our findings suggest that
      monocyte/macrophage recruitment and the systemic MCP-1 signal pathway contribute
      to progression of chronic pancreatitis, and that blockade of MCP-1 may suppress
      the development of pancreatic fibrosis.

PMID- 16284290
TI  - Paneth cells: their role in innate immunity and inflammatory disease.

PMID- 16284292
TI  - How can a migraine cause faecal incontinence?

PMID- 16284289
TI  - Opposing effects of oestradiol and progesterone on intracellular pathways and
      activation processes in the oxidative stress induced activation of cultured rat
      hepatic stellate cells.
AB  - BACKGROUND: Oxidative stress, including the generation of reactive oxygen species
      (ROS), is involved in hepatofibrogenesis. The authors' previous studies have
      shown that oestradiol suppresses hepatic fibrosis in animal models and attenuates
      the activation of cultured rat hepatic stellate cells (HSCs), which possess
      oestrogen receptor subtype beta and are also activated by ROS. AIMS: To define
      the mechanisms by which female sex hormones play an antifibrogenic role in
      activated HSCs, the effects of oestradiol and progesterone on ROS generation
      processes and intracellular pathways, leading to the activation of HSCs
      undergoing oxidative stress, was examined. METHODS: HSCs, isolated from rats,
      were cultured for 7 days with oestradiol or progesterone for 24 hours as
      pretreatment, and oxidative stress was then induced by exposure to low doses of
      hydrogen peroxide for another 24 hours. RESULTS: Oestradiol inhibited ROS
      generation and antioxidant enzyme loss via the suppression of NADH/NADPH oxidase
      activity, and attenuated hydrogen peroxide induced transforming growth factor
      beta1 (TGF-beta1) expression, HSC proliferation and transformation, and the
      activation of mitogen activated protein kinase (MAPK) pathways and transcription
      factors. Progesterone exerted a stimulatory effect through the progesterone
      receptor on the induction of ROS generation processes and intracellular pathways,
      resulting in TGF-beta1 expression and HSC activation, and fibrogenic effects were
      inhibited by oestradiol. CONCLUSION: These findings show for the first time that
      oestradiol inhibits the activation of transcription factors by suppressing ROS
      generation processes and the MAPK pathways, and inactivates the downstream
      transcription processes involved in TGF-beta1 expression and HSC activation,
      whereas progesterone acts in opposition to the favourable effects of oestradiol
      and its effects are blocked by oestradiol.

PMID- 16284293
TI  - Severe recurrent Crohn's disease of the ileocolonic anastomosis disappearing
      completely with antibacterial therapy.

PMID- 16284291
TI  - Symptom association analysis in ambulatory gastro-oesophageal reflux monitoring.

PMID- 16284294
TI  - Pitfalls in diagnosing acute pancreatitis.

PMID- 16284295
TI  - Antiapoptosis action of aged garlic extract (AGE) protects epithelial cells from
      methotrexate induced injury.

PMID- 16284296
TI  - A new entity of hereditary colorectal cancer.

PMID- 16284297
TI  - Endocinch treatment for GORD: where it stands.

PMID- 16284298
TI  - Tuberculous colitis.

PMID- 16284299
TI  - Epithelial cells in bone marrow: do they matter?

PMID- 16284300
TI  - PMS2 mutations in childhood cancer.

PMID- 16284301
TI  - Symptomatic eosinophilic gastritis cured with Helicobacter pylori eradication.

PMID- 16284302
TI  - First case of paralytic intestinal ileus after double balloon enteroscopy.

PMID- 16284303
TI  - Mechanism of action of a novel human ether-a-go-go-related gene channel
      activator.
AB  - 1,3-Bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643) is a newly discovered
      activator of human ether-a-go-go-related gene (hERG) K(+) channels. Here, we
      characterize the effects of this compound on cloned hERG channels heterologously
      expressed in Xenopus laevis oocytes. When assessed with 2-s depolarizations,
      NS1643 enhanced the magnitude of wild-type hERG current in a concentration- and
      voltage-dependent manner with an EC(50) of 10.4 microM at -10 mV. The fully
      activated current-voltage relationship revealed that the drug increased outward
      but not inward currents, consistent with altered inactivation gating. NS1643
      shifted the voltage dependence of inactivation by +21 mV at 10 microM and +35 mV
      at 30 microM, but it did not alter the voltage dependence of activation of hERG
      channels. The effects of the drug on three inactivation-deficient hERG mutant
      channels (S620T, S631A, and G628C/S631C) were determined. In the absence of
      channel inactivation, NS1643 did not enhance hERG current magnitude. The agonist
      activity of NS1643 was facilitated by mutations (F656 to Val, Met, or Thr) that
      are known to greatly attenuate channel inhibition by hERG blockers. We conclude
      that NS1643 is a partial agonist of hERG channels and that the mechanism of
      activation is reduced channel inactivation.

PMID- 16284304
TI  - Heat- and anesthesia-induced malignant hyperthermia in an RyR1 knock-in mouse.
AB  - Malignant hyperthermia (MH) is a life-threatening disorder characterized by
      skeletal muscle rigidity and elevated body temperature in response to halogenated
      anesthetics such as isoflurane or halothane. Mutation of tyrosine 522 of RyR1
      (the predominant skeletal muscle calcium release channel) to serine has been
      associated with human malignant hyperthermia. In the present study, mice created
      harboring this mutation were found to represent the first murine model of human
      malignant hyperthermia. Mice homozygous for the Y522S mutation exhibit skeletal
      defects and die during embryonic development or soon after birth. Heterozygous
      mice, which correspond to the human occurrence of this mutation, are MH
      susceptible, experiencing whole body contractions and elevated core temperatures
      in response to isoflurane exposure or heat stress. Skeletal muscles from
      heterozygous mice exhibit increased susceptibility to caffeine- and heat-induced
      contractures in vitro. In addition, the heterozygous expression of the mutation
      results in enhanced RyR1 sensitivity to activation by temperature, caffeine, and
      voltage but not uncompensated sarcoplasmic reticulum calcium leak or store
      depletion. We conclude that the heterozygous expression of the Y522S mutation
      confers susceptibility to both heat- and anesthetic-induced MH responses.

PMID- 16284305
TI  - The Arabidopsis thaliana SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASES1 and 2
      control male sporogenesis.
AB  - The Arabidopsis thaliana SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) family
      of plasma membrane receptors consists of five closely related members. The SERK1
      and SERK2 genes show a complex expression pattern throughout development. Both
      are expressed in anther primordia up to the second parietal division. After this
      point, expression ceases in the sporocytes and is continued in the tapetum and
      middle layer precursors. Single knockout mutants of SERK1 and SERK2 show no
      obvious phenotypes. Double mutants of SERK1 and SERK2 are completely male sterile
      due to a failure in tapetum specification. Fertility can be restored by a single
      copy of either gene. The SERK1 and SERK2 proteins can form homodimers or
      heterodimers in vivo, suggesting they are interchangeable in the SERK1/SERK2
      signaling complex.

PMID- 16284306
TI  - Arabidopsis SOMATIC EMBRYOGENESIS RECEPTOR KINASES1 and 2 are essential for
      tapetum development and microspore maturation.
AB  - Among the >200 members of the leucine-rich repeat receptor kinase family in
      Arabidopsis thaliana, only a few have been functionally characterized. Here, we
      report a critical function in anther development for the SOMATIC EMBRYOGENESIS
      RECEPTOR KINASE1 (SERK1) and SERK2 genes. Both SERK1 and SERK2 are expressed
      widely in locules until stage 6 anthers and are more concentrated in the tapetal
      cell layer later. Whereas serk1 and serk2 single insertion mutants did not show
      developmental phenotypes, serk1 serk2 double mutants were not able to produce
      seeds because of a lack of pollen development in mutant anthers. In young buds,
      double mutant anthers developed normally, but serk1 serk2 microsporangia produced
      more sporogenous cells that were unable to develop beyond meiosis. Furthermore,
      serk1 serk2 double mutants developed only three cell layers surrounding the
      sporogenous cell mass, whereas wild-type anthers developed four cell layers.
      Further confocal microscopic and molecular analyses showed that serk1 serk2
      double mutant anthers lack development of the tapetal cell layer, which accounts
      for the microspore abortion and male sterility. Taken together, these findings
      demonstrate that the SERK1 and SERK2 receptor kinases function redundantly as an
      important control point for sporophytic development controlling male gametophyte
      production.

PMID- 16284307
TI  - Functional genomic analysis of the AUXIN/INDOLE-3-ACETIC ACID gene family members
      in Arabidopsis thaliana.
AB  - Auxin regulates various aspects of plant growth and development. The AUXIN/INDOLE
      3-ACETIC ACID (Aux/IAA) genes encode short-lived transcriptional repressors that
      are targeted by the TRANSPORT INHIBITOR RESPONSE1/AUXIN RECEPTOR F-BOX proteins.
      The Aux/IAA proteins regulate auxin-mediated gene expression by interacting with
      members of the AUXIN RESPONSE FACTOR protein family. Aux/IAA function is poorly
      understood; herein, we report the identification and characterization of
      insertion mutants in 12 of the 29 Aux/IAA family members. The mutants show no
      visible developmental defects compared with the wild type. Double or triple
      mutants of closely related Aux/IAA genes, such as iaa8-1 iaa9-1 or iaa5-1 iaa6-1
      iaa19-1, also exhibit wild-type phenotypes. Global gene expression analysis
      reveals that the molecular phenotypes of auxin-treated and untreated light-grown
      seedlings are unaffected in the iaa17-6 and iaa5-1 iaa6-1 iaa19-1 mutants. By
      contrast, similar analysis with the gain-of-function axr3-1/iaa17-1 mutant
      seedlings reveals dramatic changes in basal and auxin-induced gene expression
      compared with the wild type. Expression of several type-A ARABIDOPSIS RESPONSE
      REGULATOR genes and a number of genes involved in cell wall biosynthesis and
      degradation is repressed in axr3-1/iaa17-1. The data suggest extensive functional
      redundancy among Aux/IAA gene family members and that enhanced stability of the
      AXR3/IAA17 protein severely alters the molecular phenotype, resulting in
      developmental defects.

PMID- 16284308
TI  - PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1 is a plant-specific SEC12-related
      protein that enables the endoplasmic reticulum exit of a high-affinity phosphate
      transporter in Arabidopsis.
AB  - PHOSPHATE TRANSPORTER1 (PHT1) genes encode phosphate (Pi) transporters that play
      a fundamental role in Pi acquisition and remobilization in plants. Mutation of
      the Arabidopsis thaliana PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1 (PHF1)
      impairs Pi transport, resulting in the constitutive expression of many Pi
      starvation-induced genes, increased arsenate resistance, and reduced Pi
      accumulation. PHF1 expression was detected in all tissues, particularly in roots,
      flowers, and senescing leaves, and was induced by Pi starvation, thus mimicking
      the expression patterns of the whole PHT1 gene family. PHF1 was localized in
      endoplasmic reticulum (ER), and mutation of PHF1 resulted in ER retention and
      reduced accumulation of the plasma membrane PHT1;1 transporter. By contrast, the
      PIP2A plasma membrane protein was not mislocalized, and the secretion of Pi
      starvation-induced RNases was not affected in the mutant. PHF1 encodes a plant
      specific protein structurally related to the SEC12 proteins of the early
      secretory pathway. However, PHF1 lacks most of the conserved residues in SEC12
      proteins essential as guanine nucleotide exchange factors. Although it functions
      in early secretory trafficking, PHF1 likely evolved a novel mechanism
      accompanying functional specialization on Pi transporters. The identification of
      PHF1 reveals that plants are also endowed with accessory proteins specific for
      selected plasma membrane proteins, allowing their exit from the ER, and that
      these ER exit cofactors may have a phylum-specific origin.

PMID- 16284309
TI  - Localization of the tomato bushy stunt virus replication protein p33 reveals a
      peroxisome-to-endoplasmic reticulum sorting pathway.
AB  - Tomato bushy stunt virus (TBSV), a positive-strand RNA virus, causes extensive
      inward vesiculations of the peroxisomal boundary membrane and formation of
      peroxisomal multivesicular bodies (pMVBs). Although pMVBs are known to contain
      protein components of the viral membrane-bound RNA replication complex, the
      mechanisms of protein targeting to peroxisomal membranes and participation in
      pMVB biogenesis are not well understood. We show that the TBSV 33-kD replication
      protein (p33), expressed on its own, targets initially from the cytosol to
      peroxisomes, causing their progressive aggregation and eventually the formation
      of peroxisomal ghosts. These altered peroxisomes are distinct from pMVBs; they
      lack internal vesicles and are surrounded by novel cytosolic vesicles that
      contain p33 and appear to be derived from evaginations of the peroxisomal
      boundary membrane. Concomitant with these changes in peroxisomes, p33 and
      resident peroxisomal membrane proteins are relocalized to the peroxisomal
      endoplasmic reticulum (pER) subdomain. This sorting of p33 is disrupted by the
      coexpression of a dominant-negative mutant of ADP-ribosylation factor1,
      implicating coatomer in vesicle formation at peroxisomes. Mutational analysis of
      p33 revealed that its intracellular sorting is also mediated by several targeting
      signals, including three peroxisomal targeting elements that function
      cooperatively, plus a pER targeting signal resembling an Arg-based motif
      responsible for vesicle-mediated retrieval of escaped ER membrane proteins from
      the Golgi. These results provide insight into virus-induced intracellular
      rearrangements and reveal a peroxisome-to-pER sorting pathway, raising new
      mechanistic questions regarding the biogenesis of peroxisomes in plants.

PMID- 16284310
TI  - An Arabidopsis endo-1,4-beta-D-glucanase involved in cellulose synthesis
      undergoes regulated intracellular cycling.
AB  - The synthesis of cellulose microfibrils requires the presence of a membrane-bound
      endo-1,4-beta-D-glucanase, KORRIGAN1 (KOR1). Although the exact biochemical role
      of KOR1 in cellulose synthesis is unknown, we used the protein as a marker to
      explore the potential involvement of subcellular transport processes in cellulose
      synthesis. Using immunofluorescence and a green fluorescent protein (GFP)-KOR1
      fusion that complemented the phenotype conferred by the kor1-1 mutant, we
      investigated the distribution of KOR1 in epidermal cells in the root meristem.
      KOR1 was localized in intracellular compartments corresponding to a heterogeneous
      population of organelles, which comprised the Golgi apparatus, FM4-64-labeled
      compartments referred to as early endosomes, and, in the case of GFP-KOR1, the
      tonoplast. Inhibition of cellulose synthesis by isoxaben promoted a net
      redistribution of GFP-KOR1 toward a homogeneous population of compartments,
      distinct from early endosomes, which were concentrated close to the plasma
      membrane facing the root surface. A redistribution of GFP-KOR1 away from early
      endosomes was also observed in the same cells at later stages of cell elongation.
      A subpopulation of GFP-KOR1-containing compartments followed trajectories along
      the plasma membrane, and this motility required intact microtubules. These
      observations demonstrate that the deposition of cellulose, like chitin synthesis
      in yeast, involves the regulated intracellular cycling of at least one enzyme
      required for its synthesis.

PMID- 16284311
TI  - Conservation and divergence of light-regulated genome expression patterns during
      seedling development in rice and Arabidopsis.
AB  - Genome-wide 70-mer oligonucleotide microarrays of rice (Oryza sativa) and
      Arabidopsis thaliana were used to profile genome expression changes during light
      regulated seedling development. We estimate that the expression of approximately
      20% of the genome in both rice and Arabidopsis seedlings is regulated by white
      light. Qualitatively similar expression profiles from seedlings grown under
      different light qualities were observed in both species; however, a
      quantitatively weaker effect on genome expression was observed in rice. Most
      metabolic pathways exhibited qualitatively similar light regulation in both
      species with a few species-specific differences. Global comparison of expression
      profiles between rice and Arabidopsis reciprocal best-matched gene pairs revealed
      a higher correlation of genome expression patterns in constant light than in
      darkness, suggesting that the genome expression profile of photomorphogenesis is
      more conserved. Transcription factor gene expression under constant light
      exposure was poorly conserved between the two species, implying a faster-evolving
      rate of transcription factor gene expression in light-grown plants. Organ
      specific expression profiles during seedling photomorphogenesis provide genome
      level evidence for divergent light effects in different higher plant organs.
      Finally, overrepresentation of specific promoter motifs in root- and leaf
      specific light-regulated genes in both species suggests that these cis-elements
      are important for gene expression responses to light.

PMID- 16284312
TI  - NAB1 is an RNA binding protein involved in the light-regulated differential
      expression of the light-harvesting antenna of Chlamydomonas reinhardtii.
AB  - Photosynthetic organisms respond to changes in ambient light by modulating the
      size and composition of their light-harvesting complexes, which in the case of
      the green alga Chlamydomonas reinhardtii consists of >15 members of a large
      extended family of chlorophyll binding subunits. How their expression is
      coordinated is unclear. Here, we describe the analysis of an insertion mutant,
      state transitions mutant3 (stm3), which we show has increased levels of LHCBM
      subunits associated with the light-harvesting antenna of photosystem II. The
      mutated nuclear gene in stm3 encodes the RNA binding protein NAB1 (for putative
      nucleic acid binding protein). In vitro and in vivo RNA binding and protein
      expression studies have confirmed that NAB1 differentially binds to LHCBM mRNA in
      a subpolysomal high molecular weight RNA-protein complex. Binding of NAB1
      stabilizes LHCBM mRNA at the preinitiation level via sequestration and thereby
      represses translation. The specificity and affinity of binding are determined by
      an RNA sequence motif similar to that used by the Xenopus laevis translation
      repressor FRGY2, which is conserved to varying degrees in the LHCBM gene family.
      We conclude from our results that NAB1 plays an important role in controlling the
      expression of the light-harvesting antenna of photosystem II at the
      posttranscriptional level. The similarity of NAB1 and FRGY2 of Xenopus implies
      the existence of similar RNA-masking systems in animals and plants.

PMID- 16284323
TI  - Guidance on the Competition Commission's recommendations.

PMID- 16284314
TI  - Arbuscular mycorrhizal fungi elicit a novel intracellular apparatus in Medicago
      truncatula root epidermal cells before infection.
AB  - The penetration of arbuscular mycorrhizal (AM) fungi through the outermost root
      tissues of the host plant is a critical step in root colonization, ultimately
      leading to the establishment of this ecologically important endosymbiotic
      association. To evaluate the role played by the host plant during AM infection,
      we have studied in vivo cellular dynamics within Medicago truncatula root
      epidermal cells using green fluorescent protein labeling of both the plant
      cytoskeleton and the endoplasmic reticulum. Targeting roots with Gigaspora hyphae
      has revealed that, before infection, the epidermal cell assembles a transient
      intracellular structure with a novel cytoskeletal organization. Real-time
      monitoring suggests that this structure, designated the prepenetration apparatus
      (PPA), plays a central role in the elaboration of the apoplastic interface
      compartment through which the fungus grows when it penetrates the cell lumen. The
      importance of the PPA is underlined by the fact that M. truncatula dmi (for
      doesn't make infections) mutants fail to assemble this structure. Furthermore,
      PPA formation in the epidermis can be correlated with DMI-dependent
      transcriptional activation of the Medicago early nodulin gene ENOD11. These
      findings demonstrate how the host plant prepares and organizes AM infection of
      the root, and both the plant-fungal signaling mechanisms involved and the
      mechanistic parallels with Rhizobium infection in legume root hairs are
      discussed.

PMID- 16284319
TI  - Veterinary Medicines Regulations 2005.

PMID- 16284327
TI  - Fifth outbreak of disease associated with bovine viral diarrhoea virus type 2.

PMID- 16284313
TI  - AREB1 is a transcription activator of novel ABRE-dependent ABA signaling that
      enhances drought stress tolerance in Arabidopsis.
AB  - ABSCISIC ACID-RESPONSIVE ELEMENT BINDING PROTEIN1 (AREB1) (i.e., ABF2) is a basic
      domain/leucine zipper transcription factor that binds to the abscisic acid (ABA)
      responsive element (ABRE) motif in the promoter region of ABA-inducible genes.
      Here, we show that expression of the intact AREB1 gene on its own is insufficient
      to lead to expression of downstream genes under normal growth conditions. To
      overcome the masked transactivation activity of AREB1, we created an activated
      form of AREB1 (AREB1DeltaQT). AREB1DeltaQT-overexpressing plants showed ABA
      hypersensitivity and enhanced drought tolerance, and eight genes with two or more
      ABRE motifs in the promoter regions in two groups were greatly upregulated: late
      embryogenesis abundant class genes and ABA- and drought stress-inducible
      regulatory genes. By contrast, an areb1 null mutant and a dominant loss-of
      function mutant of AREB1 (AREB1:RD) with a repression domain exhibited ABA
      insensitivity. Furthermore, AREB1:RD plants displayed reduced survival under
      dehydration, and three of the eight greatly upregulated genes were downregulated,
      including genes for linker histone H1 and AAA ATPase, which govern gene
      expression and multiple cellular activities through protein folding,
      respectively. Thus, these data suggest that AREB1 regulates novel ABRE-dependent
      ABA signaling that enhances drought tolerance in vegetative tissues.

PMID- 16284329
TI  - Shedding of Mycobacterium bovis in the nasal mucus of cattle infected
      experimentally with tuberculosis by the intranasal and intratracheal routes.
AB  - Four groups of six calves were infected experimentally with either a low dose of
      approximately 10(4) colony-forming units (cfu) or a high dose of approximately
      10(6) cfu of Mycobacterium bovis. Each dose was delivered by the intranasal and
      intratracheal routes. More severe disease was observed in the groups inoculated
      with the high dose. Visible lesions were identified in 21 of the 24 animals, all
      of which also gave positive skin tests and interferon-gamma (IFN-gamma)
      responses. Nasal shedding was detected in 15 of the 24 animals and the frequency
      of shedding was influenced by both the route and the dose of infection; no
      shedding was observed in the group infected intratracheally with the low dose.
      Two of the 15 confirmed shedders had no visible lesions at postmortem
      examination; both of these calves gave IFN-gamma responses but only one was skin
      test positive.

PMID- 16284330
TI  - Variability in the eruption of the permanent incisor teeth in sheep.
AB  - The incisor teeth of 176 sheep of six breeds were inspected every two to three
      months for a year to record the shedding of the deciduous teeth and the eruption
      of the permanent teeth. In all the breeds the permanent central incisors erupted
      at between 12 and 18 months of age. In 96 per cent of the sheep the permanent
      middle incisors erupted at between 18 and 26 months; and in 92 per cent the
      permanent lateral incisors erupted at between 24 and 36 months of age. The
      permanent corner teeth erupted at between 32 and 44 months in 96 per cent of the
      sheep. The gingival redness and swelling accompanying the eruption of a permanent
      tooth disappeared within two months. In 14 cases two pairs of incisors erupted
      during the year, in 18 cases the incisors erupted asymmetrically, and in 22 cases
      no incisors erupted. Rotation of one incisor was observed in five sheep and was
      combined with dental deviation in one.

PMID- 16284332
TI  - PrP genotyping of sheep breeds in Slovakia.

PMID- 16284331
TI  - Giardia duodenalis and Cryptosporidium parvum infections in adult goats and their
      implications for neonatal kids.
AB  - During the kidding season between January and April 2003, 10 farms were selected
      and divided into two groups of five. The farms in group A had had serious
      diarrhoeal illness and losses in neonatal kids the previous year, and there were
      Cryptosporidium parvum infections in kids associated with diarrhoea during the
      survey. On the farms in group B, there was no history of diarrhoeal disease the
      previous year and neither C parvum oocysts nor diarrhoea were detected in
      neonatal kids during the survey. Faecal samples were collected once from 10 adult
      goats aged between one and seven years on each farm. To assess more accurately
      the pattern of output of oocysts of C parvum and cysts of Giardia duodenalis by
      periparturient adult goats, one farm was selected from each group, faecal samples
      were collected weekly before and after kidding from 12 goats on the farm in group
      A and from 10 goats on the farm in group B. There was no significant difference
      in the prevalence of G duodenalis cysts between the group A farms (14 per cent)
      and the group B farms (12 per cent), and the numbers of cysts excreted ranged
      from 143 to 400 cysts per gram of faeces (cpg) on the group A farms and 72 to 334
      cpg on the group B farms. There was a significant difference (P=0.03) in the
      prevalence of C parvum oocysts at the group level between the group A farms (20
      per cent) and the group B farms (6 per cent). All the adult goats excreted cysts
      and oocysts at some date around the kidding period; the number of animals
      excreting cysts of G duodenalis or oocysts of C parvum increased when they gave
      birth, and seven to 10 times more cysts and oocysts were shed in the three weeks
      around kidding than in the period more than three weeks from kidding (P<0.001).

PMID- 16284333
TI  - Ectopic cartilage formation of unknown origin in the plantar pouch of the
      tarsocrural joint in a yearling.

PMID- 16284334
TI  - Chlamydophila abortus-induced keratoconjunctivitis in a dog.

PMID- 16284335
TI  - Shoulder injuries in veterinary surgeons.

PMID- 16284336
TI  - Fire action causes alarm.

PMID- 16284337
TI  - Non-therapeutic docking of dogs' tails.

PMID- 16284338
TI  - LVI rates.

PMID- 16284339
TI  - Suicide and mental health issues in the profession.

PMID- 16284340
TI  - Microarray gene expression data with linked survival phenotypes: diffuse large-B
      cell lymphoma revisited.
AB  - Diffuse large-B-cell lymphoma (DLBCL) is an aggressive malignancy of mature B
      lymphocytes and is the most common type of lymphoma in adults. While treatment
      advances have been substantial in what was formerly a fatal disease, less than
      50% of patients achieve lasting remission. In an effort to predict treatment
      success and explain disease heterogeneity clinical features have been employed
      for prognostic purposes, but have yielded only modest predictive performance.
      This has spawned a series of high-profile microarray-based gene expression
      studies of DLBCL, in the hope that molecular-level information could be used to
      refine prognosis. The intent of this paper is to reevaluate these microarray
      based prognostic assessments, and extend the statistical methodology that has
      been used in this context. Methodological challenges arise in using patients'
      gene expression profiles to predict survival endpoints on account of the large
      number of genes and their complex interdependence. We initially focus on the
      Lymphochip data and analysis of Rosenwald et al. (2002). After describing
      relationships between the analyses performed and gene harvesting (Hastie et al.,
      2001a), we argue for the utility of penalized approaches, in particular least
      angle regression-least absolute shrinkage and selection operator (Efron et al.,
      2004). While these techniques have been extended to the proportional
      hazards/partial likelihood framework, the resultant algorithms are
      computationally burdensome. We develop residual-based approximations that
      eliminate this burden yet perform similarly. Comparisons of predictive accuracy
      across both methods and studies are effected using time-dependent receiver
      operating characteristic curves. These indicate that gene expression data, in
      turn, only delivers modest predictions of posttherapy DLBCL survival. We conclude
      by outlining possibilities for further work.

PMID- 16284341
TI  - Autoantibodies to opsonins of apoptotic cells in systemic lupus erythematosus.

PMID- 16284342
TI  - High dose chemotherapy and syngeneic stem cell transplantation in a patient with
      refractory rheumatoid arthritis: poor response associated with persistence of
      host autoantibodies and synovial abnormalities.
AB  - BACKGROUND: Immunoablative therapy combined with haematopoietic stem cell
      transplantation (SCT) is a possible treatment for patients with severe rheumatoid
      arthritis (RA). CASE REPORT: A patient with rheumatoid factor positive,
      progressively erosive RA, refractive to treatment, was treated with high dose
      cyclophosphamide, followed by reinfusion of an unmanipulated peripheral blood
      graft derived from her identical twin sister. The clinical response was
      unsatisfactory, necessitating reinstitution of treatment with disease modifying
      antirheumatic drugs, which was associated with persistence of host serum
      autoantibodies and a cellular infiltrate in synovium, notably of plasma cells.
      DISCUSSION: The effectiveness of syngeneic SCT may be critically dependent on the
      degree of immunoablation achieved or on the composition of the graft.

PMID- 16284343
TI  - Joint restriction in an unhappy teenager.

PMID- 16284344
TI  - Relapse of autoimmune diseases after autologous T cell depleted stem cell
      transplantation may be triggered by T cells recently emigrated from the thymus.

PMID- 16284345
TI  - Altered influenza virus haemagglutinin peptides inhibit T cell responses to type
      II collagen in rheumatoid arthritis.

PMID- 16284346
TI  - Relationship between 5,10-methylenetetrahydrofolate reductase C677T gene
      polymorphism and methotrexate related toxicity in patients with autoimmune
      diseases receiving folic acid supplementation.

PMID- 16284347
TI  - Primary antiphospholipid syndrome: a unique presentation with multiple visceral
      aneurysms.

PMID- 16284348
TI  - A family with diffuse idiopathic skeletal hyperostosis.

PMID- 16284349
TI  - Antiphospholipid antibodies in patients with scleroderma: prevalence and clinical
      significance.

PMID- 16284351
TI  - Peripheral neuropathy in patients with systemic rheumatic diseases treated with
      leflunomide.

PMID- 16284350
TI  - Remitting seronegative symmetrical synovitis with pitting oedema/polymyalgia
      rheumatica after infection with Mycoplasma pneumoniae.

PMID- 16284352
TI  - Vasculitis, antiphospholipid antibodies, and renal artery stenosis.

PMID- 16284353
TI  - Therapeutic interleukin (IL) 1 blockade normalises increased IL1 beta and
      decreased tumour necrosis factor alpha and IL10 production in blood mononuclear
      cells of a patient with CINCA syndrome.

PMID- 16284354
TI  - Reversible posterior leucoencephalopathy in scleroderma.

PMID- 16284355
TI  - Experimental infection with Plasmodium falciparum does not result in the
      induction of anticardiolipin antibodies in healthy volunteers.

PMID- 16284356
TI  - Population based studies of biological antirheumatic drug use in southern Sweden:
      comparison with pharmaceutical sales.

PMID- 16284357
TI  - Anti-cyclic citrullinated peptide antibodies in patients with rheumatoid
      arthritis treated with anti-tumour necrosis factor agents.

PMID- 16284358
TI  - Uveitis in young adults with juvenile idiopathic arthritis.

PMID- 16284359
TI  - Chronic ethanol ingestion increases superoxide production and NADPH oxidase
      expression in the lung.
AB  - Alcohol abuse increases the incidence of acute respiratory distress syndrome and
      causes oxidative stress and cellular dysfunction in the lung. The mechanisms of
      ethanol (EtOH)-induced oxidative stress in the lung remain to be defined. Chronic
      alcohol ingestion has been associated with increased renin-angiotensin system
      (RAS) activity. Therefore, the current study investigated the ability of
      lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, to modulate
      oxidative stress in the lung after chronic EtOH ingestion in a well-established
      rat model. Male Sprague-Dawley rats were fed liquid diets containing EtOH (36% of
      calories) or maltose-dextrin as an isocaloric substitution for EtOH (Control) for
      6 wk. Selected animals were also treated with lisinopril (3 mg/liter) for 6 wk.
      Chronic EtOH ingestion increased bronchoalveolar lavage fluid glutathione
      disulfide levels and superoxide formation in lung parenchyma. These effects of
      EtOH were attenuated by lisinopril treatment. Chronic EtOH ingestion failed to
      increase ACE expression or angiotensin II levels in lung homogenates, but
      increased angiotensinogen, angiotensin II type 1 and type 2 receptor levels, and
      ACE activity. Chronic EtOH ingestion also increased the levels of the NADPH
      oxidase subunit, gp91phox, an effect that was attenuated by lisinopril, but had
      no effect on lung p22phox or p47phox levels. These findings suggest that EtOH
      mediated RAS activation plays an important role in pulmonary oxidative stress and
      provide new insights into mechanisms by which EtOH causes oxidative stress in the
      lung and potential strategies of lung protection through ACE inhibition.

PMID- 16284361
TI  - SERCA pump inhibitors do not correct biosynthetic arrest of deltaF508 CFTR in
      cystic fibrosis.
AB  - Deletion of phenylalanine 508 (deltaF508) accounts for nearly 70% of all
      mutations that occur in the cystic fibrosis transmembrane conductance regulator
      (CFTR). The deltaF508 mutation is a class II processing mutation that results in
      very little or no mature CFTR protein reaching the apical membrane and thus no
      cAMP-mediated Cl- conductance. Therapeutic strategies have been developed to
      enhance processing of the defective deltaF508 CFTR molecule so that a functional
      cAMP-regulated Cl- channel targets to the apical membrane.
      Sarcoplasmic/endoplasmic reticulum calcium (SERCA) inhibitors, curcumin and
      thapsigargin, have been reported to effectively correct the CF ion transport
      defects observed in the deltaF508 CF mice. We investigated the effect of these
      compounds in human airway epithelial cells to determine if they could induce
      deltaF508 CFTR maturation, and Cl- secretion. We also used Baby Hamster Kidney
      cells, heterologously expressing deltaF508 CFTR, to determine if SERCA inhibitors
      could interfere with the interaction between calnexin and CFTR and thereby
      correct the deltaF508 CFTR misfolding defect. Finally, at the whole animal level,
      we tested the ability of curcumin and thapsigargin to (1) induce Cl- secretion
      and reduce hyperabsorption of Na+ in the nasal epithelia of the deltaF508 mouse
      in vivo, and (2) induce Cl- secretion in intestine (jejunum and distal colon) and
      the gallbladder of the deltaF508 CF mouse. We conclude that curcumin and
      thapsigargin failed to induce maturation of deltaF508 CFTR, or induce Cl-
      secretion, as measured by biochemical and electrophysiologic techniques in a
      variety of model systems ranging from cultured cells to in vivo studies.

PMID- 16284363
TI  - Duration of exposure, a neglected factor in chemoprevention trials.

PMID- 16284362
TI  - T cell chemotaxis and chemokine release after Staphylococcus aureus interaction
      with polarized airway epithelium.
AB  - In response to bacterial infection, airway epithelium releases inflammatory
      mediators including cytokines and chemokines that lead to immune cell efflux and
      could stimulate the adaptive T cell immune response. The aim of our study was to
      analyze, in a double chamber culture, the chemokine changes in response to
      Staphylococcus aureus and their consequences for T cells. Our data show that S.
      aureus stimulates basolateral and apical release of IL-8 and eotaxin by airway
      epithelial cells. We also observed increased chemokine receptor expression on
      CD8+ and CD4+ T cells and enhanced chemotaxis of CD4+ T cells toward apical
      supernatant. Our data strongly suggest that S. aureus interaction with airway
      epithelium contributes to specific migration of T cells to inflamed sites.

PMID- 16284360
TI  - Differential response of dendritic cells to human metapneumovirus and respiratory
      syncytial virus.
AB  - Dendritic cells (DCs) play a pivotal role in shaping antiviral immune responses
      in the respiratory tract. Human metapneumovirus (hMPV) is a recently identified
      pathogen and like its better known relative, respiratory syncytial virus (RSV),
      has been increasingly recognized as a major cause of respiratory morbidity in
      infants and in elderly persons. In the present study, we examined susceptibility
      as well as cellular responses of human DCs to hMPV compared with RSV. Monocyte
      derived DCs (moDCs) were susceptible to infection by both viruses, but only RSV
      was able to induce a productive infection with release of viral progeny. Despite
      the fact that viral infection resulted in phenotypic maturation of moDCs, as
      shown by the upregulation of cell surface markers and antigen-presenting
      molecules (MHC I and II, CD80, CD83, CD86, CD38), RSV-infected moDCs showed a
      severely impaired capacity to stimulate CD4+ T cell proliferation. Compared with
      hMPV, RSV was a more potent inducer of inflammatory and immunomodulatory
      cytokines, including TNF-alpha, IL-6, IL-1beta, IL-10, and IL-12p70 in both moDCs
      and plasmacytoid dendritic cells (pDCs). On the other hand, hMPV, but not RSV,
      was able to trigger production of IFN-alpha by moDCs, while both viruses strongly
      induced IFN-alpha in pDCs. Finally, both viruses strikingly suppressed IFN-alpha
      production by moDCs or pDCs stimulated with synthetic dsRNA and CpG-ODN,
      respectively. The findings provide novel evidence that RSV and hMPV
      differentially activate human DCs and may use distinct mechanisms to interfere
      with the host innate and adaptive immune responses.

PMID- 16284364
TI  - Ethnicity, ancestry, and race in molecular epidemiologic research.

PMID- 16284365
TI  - The value of small observations in the era of big science.

PMID- 16284366
TI  - Methyl-CpG binding domain 1 gene polymorphisms and risk of primary lung cancer.
AB  - The methyl-CpG binding domain 1 (MBD1) protein plays an important role for
      transcriptional regulation of gene expression. Polymorphisms and haplotypes of
      the MBD1 gene may have an influence on MBD1 activity on gene expression profiles,
      thereby modulating an individual's susceptibility to lung cancer. To test this
      hypothesis, we investigated the association of MBD1 -634G>A, -501delT (-501 T/T,
      T/-, -/-), and Pro(401)Ala genotypes and their haplotypes with the risk of lung
      cancer in a Korean population. The MBD1 genotype was determined in 432 lung
      cancer patients and in 432 healthy control subjects who were frequency matched
      for age and gender. The -634GG genotype was associated with a significantly
      increased risk of overall lung cancer compared with the -634AA genotype [adjusted
      odds ratio (OR), 3.10; 95% confidence interval (95% CI), 1.24-7.75; P = 0.016].
      When analyses were stratified according to the tumor histology, the -634GG
      genotype was associated with a significantly increased risk of adenocarcinoma
      compared with the -634AA genotype (adjusted OR, 4.72; 95% CI, 1.61-13.82; P =
      0.005). For the MBD1 -501delT and Pro(401)Ala polymorphisms, the -501 T/T
      genotype was associated with a marginal significantly increased risk of
      adenocarcinoma compared with the -501(-/-) genotype (adjusted OR, 2.07; 95% CI,
      1.02-4.20; P = 0.045), and the Pro/Pro genotype was associated with a
      significantly increased risk of adenocarcinoma compared with the Ala/Ala genotype
      (adjusted OR, 3.41; 95% CI, 1.21-9.60; P = 0.02). Consistent with the genotyping
      analyses, the -634G/-501T/(401)Pro haplotype was associated with a significantly
      increased risk of overall lung cancer and adenocarcinoma compared with the -634A/
      501(-)/(401)Ala haplotype (adjusted OR, 1.44; 95% CI, 1.08-1.91; P = 0.012 and
      P(c) = 0.048; adjusted OR, 1.75; 95% CI, 1.20-2.56; P = 0.004 and P(c) = 0.016,
      respectively). On a promoter assay, the -634A allele had significantly higher
      promoter activity compared with the -634G allele in the Chinese hamster ovary
      cells and A549 cells (P < 0.05 and P < 0.001, respectively), but the -501delT
      polymorphism did not have an effect on the promoter activity. When comparing the
      promoter activity of the MBD1 haplotypes, the -634A/-501(-) haplotype had a
      significantly higher promoter activity than the -634G/-501T haplotype (P <
      0.001). These results suggest that the MBD1 -634G>A, -501delT, and Pro(401)Ala
      polymorphisms and their haplotypes contribute to the genetic susceptibility for
      lung cancer and particularly for adenocarcinoma.

PMID- 16284367
TI  - Interactions among smoking, obesity, and symptoms of acid reflux in Barrett's
      esophagus.
AB  - BACKGROUND: Barrett's esophagus, a metaplastic precursor to esophageal
      adenocarcinoma, is becoming increasingly prevalent in many populations. Clinical
      studies suggest acid reflux causes Barrett's esophagus; however, no population
      based estimates of risk have been reported, and the role of other health factors
      in modifying risk is unclear. METHODS: We conducted a population-based case
      control study in Brisbane, Australia. Cases were 167 patients with histologically
      confirmed Barrett's esophagus diagnosed between February and December 2003. Age
      matched and sex-matched controls (n = 261) were randomly selected from a
      population register. Data on exposure to self-reported symptoms of acid reflux,
      smoking, obesity, and other factors were collected through self-completed
      questionnaires followed by telephone interview. Risks of Barrett's esophagus and
      Barrett's esophagus with dysplasia associated with these exposures were estimated
      by the odds ratio (OR) and 95% confidence interval (95% CI), both crude and
      adjusted for other factors. RESULTS: Self-reported weekly episodes of acid reflux
      were associated with greatly increased risks of Barrett's esophagus (adjusted OR,
      29.7; 95% CI, 12.2-72.6) and Barrett's esophagus with dysplasia (OR, 59.7; 95%
      CI, 18.5-193). Smoking was also associated with risk of Barrett's esophagus. We
      found evidence of interactions between symptoms of acid reflux and smoking and
      obesity. Obese people with self-reported symptoms of acid reflux had markedly
      higher risks of Barrett's esophagus (OR, 34.4; 95% CI, 6.3-188) than people with
      reflux alone (OR, 9.3; 95% CI, 1.4-62.2) or obesity alone (OR, 0.7; 95% CI, 0.2
      2.4). Similarly, those reporting both acid reflux symptoms and smoking were at
      substantially higher risks of Barrett's esophagus (OR, 51.4; 95% CI, 14.1-188)
      than those reporting acid reflux or smoking alone. CONCLUSIONS: Although history
      of symptoms of acid reflux is the principle factor associated with Barrett's
      esophagus, risks are substantially increased by obesity and smoking.

PMID- 16284368
TI  - Interleukin-8 promoter polymorphism increases the risk of atrophic gastritis and
      gastric cancer in Japan.
AB  - Host genetic susceptibility may influence gastric carcinogenesis caused by
      Helicobacter pylori infection. We aimed to clarify the relationship of
      interleukin (IL)-8 polymorphism with the risk of atrophic gastritis and gastric
      cancer. We examined IL-8 -251 T > A, IL-1B -511 C > T, and IL-1RN intron 2
      polymorphisms in 252 healthy controls, 215 individuals with atrophic gastritis,
      and 396 patients with gastric cancer. We also investigated the effect of the IL-8
      polymorphism on IL-8 production and histologic degree of gastritis in
      noncancerous gastric mucosa. Although no correlation was found in the analysis of
      the IL-1B and IL-1RN polymorphisms, IL-8 -251 A/A genotype held a higher risk of
      atrophic gastritis [odds ratio (OR), 2.35; 95% confidence interval (CI), 1.12
      4.94] and gastric cancer (OR, 2.22; 95% CI, 1.08-4.56) compared with the T/T
      genotype. We also found that the A/A genotype increased the risk of upper-third
      location (OR, 3.66; 95% CI, 1.46-9.17), diffuse (OR, 2.79; 95% CI, 1.21-6.39),
      poorly differentiated (OR, 2.70; 95% CI, 1.14-6.38), lymph node (OR, 2.50; 95%
      CI, 1.01-6.20), and liver metastasis (OR, 5.63; 95% CI, 1.06-30.04), and p53
      mutated (OR, 1.91; 95% CI, 1.13-3.26) subtypes of gastric cancer. The A/A and A/T
      genotypes were significantly associated with higher levels of IL-8 protein
      compared with the T/T genotype. Neutrophil infiltration score was significantly
      higher in the A/A genotype than in the T/T genotype. In conclusion, we showed
      that the IL-8 -251 T > A polymorphism is associated with higher expression of IL
      8 protein, more severe neutrophil infiltration, and increased risk of atrophic
      gastritis and gastric cancer.

PMID- 16284369
TI  - Family history assessment to detect increased risk for colorectal cancer:
      conceptual considerations and a preliminary economic analysis.
AB  - BACKGROUND: Although the rationale for earlier screening of persons with a family
      history of colorectal cancer is plausible, there is no direct evidence that
      earlier assessment is either effective or cost-effective. OBJECTIVE: To estimate
      the clinical and economic effect of using family history assessment to identify
      persons for colorectal cancer screening before age 50. METHODS: We developed a
      decision model to compare costs and outcomes for two scenarios: (a) standard
      population screening starting at age 50; (b) family history assessment at age 40,
      followed by screening colonoscopy at age 40 for those with a suggestive family
      history of colorectal cancer. The analysis was conducted using the health insurer
      perspective. RESULTS: Using U.S. population estimates, 22 million would be
      eligible for family history assessment, and one million would be eligible for
      early colonoscopy; 2,834 invasive cancers would be detected, and 29,331 life
      years would be gained. The initial program cost would be USD $900 million. The
      discounted cost per life year gained of family history assessment versus no
      assessment equals USD $58,228. The results were most sensitive to the life
      expectancy benefit from earlier screening, the cost of colonoscopy, and the
      relative risk of colon cancer in those with a family history. CONCLUSIONS: The
      cost-effectiveness of family history assessment for colorectal cancer approaches
      that of other widely accepted technologies; yet, the results are sensitive to
      several assumptions where better data are needed. Because of the relatively high
      prevalence of family history in the population, careful analysis and empirical
      data are needed.

PMID- 16284370
TI  - DNA repair polymorphisms and risk of colorectal adenomatous or hyperplastic
      polyps.
AB  - Genetic variability in DNA repair genes may contribute to differences in DNA
      repair capacity and susceptibility to cancer, especially in the presence of
      exposures such as smoking. In a Minnesota-based case-control study of cases with
      only adenomatous polyps (n = 384), only hyperplastic polyps (n = 191), or both
      types of polyps (n = 119) versus polyp-free controls (n = 601), we investigated
      the role of polymorphisms in the DNA repair genes O(6)-methylguanine
      methyltransferase (MGMT; p.L84F and p.I143V), XPD (p.D312N and p.K751Q), and XPG
      (p.D1104H). MGMT polymorphisms were not associated with polyp risk. Overall, a
      homozygous variant XPD-combined genotype was associated with an increased risk of
      adenomatous polyps [odds ratio (OR), 1.57; 95% confidence interval (95% CI), 1.04
      2.38] and an XPGHH1104 genotype with a decreased risk of hyperplastic polyps (OR,
      0.36; 95% CI, 0.13-0.98). However, age stratification showed that the XPD
      association was present only in subjects >/=60 years old (OR, 3.77; 95% CI, 1.94
      7.35), whereas the XPG association was observed largely in subjects <60 years old
      (OR, 0.20; 95% CI, 0.05-0.91). Smokers did not have a significantly increased
      risk of adenomatous polyps in the absence of synchronous hyperplastic polyps,
      except for subjects with a homozygous variant XPD genotype or a homozygous wild
      type XPG genotype (OR, 3.93; 95% CI, 1.68-9.21 and OR, 1.59; 95% CI, 1.01-2.50,
      respectively). Smoking was associated with a statistically significant 2.5- to 6
      fold increased risk of hyperplastic polyps for individuals with most of the DNA
      repair genotypes. However, no substantial increase was observed among individuals
      who were homozygous variant for XPG (1104HH; OR, 1.38; 95% CI, 0.25-7.65). Our
      data suggest that polymorphisms in DNA repair genes may be risk factors for
      colorectal neoplasia and that they may exacerbate the effects of exposures to
      carcinogens.

PMID- 16284371
TI  - Polymorphisms in the reduced folate carrier, thymidylate synthase, or methionine
      synthase and risk of colon cancer.
AB  - Folate metabolism supports the synthesis of nucleotides as well as the transfer
      of methyl groups. Polymorphisms in folate-metabolizing enzymes have been shown to
      affect risk of colorectal neoplasia and other malignancies. Using data from a
      population-based incident case-control study (1,600 cases and 1,962 controls), we
      investigated associations between genetic variants in the reduced folate carrier
      (RFC), thymidylate synthase (TS), methionine synthase (MTR), and 5,10
      methylenetetrahydrofolate reductase (MTHFR) and colon cancer risk. The TS
      enhancer region (TSER) variant was associated with a reduced risk among men
      [2rpt/2rpt versus 3rpt/3rpt wild-type; odds ratio (OR), 0.7; 95% confidence
      interval, 0.6-0.98] but not women. When combined genotypes for both TS
      polymorphisms (TSER and 3'-untranslated region 1494delTTAAAG) were evaluated, ORs
      for variant genotypes were generally below 1.0, with statistically significantly
      reduced risks among women. Neither MTR D919G nor RFC 80G>A polymorphisms were
      associated with altered colon cancer risk. Because folate metabolism is
      characterized by interrelated reactions, we evaluated gene-gene interactions.
      Genotypes resulting in reduced MTHFR activity in conjunction with low TS
      expression were associated with a reduced risk of colon cancer. When dietary
      intakes were taken into account, individuals with at least one variant TSER
      allele (3rpt/2rpt or 2rpt/2rpt) were at reduced risk in the presence of a low
      folate intake. This study supports findings from adenoma studies indicating that
      purine synthesis may be a relevant biological mechanism linking folate metabolism
      to colon cancer risk. A pathway-based approach to data analysis is needed to help
      discern the independent and combined effects of dietary intakes and genetic
      variability in folate metabolism.

PMID- 16284372
TI  - Coexpression of beta1,6-N-acetylglucosaminyltransferase V glycoprotein substrates
      defines aggressive breast cancers with poor outcome.
AB  - Beta1,6-n-acetylglucosaminyltransferase-V (GnT-V) catalyzes the addition of
      complex oligosaccharide side chains to glycoproteins, regulating the expression
      and function of several proteins involved in tumor metastasis. We analyzed the
      expression of five cell-surface glycoprotein substrates of GnT-V, matriptase,
      beta1-integrin, epidermal growth factor receptor, lamp-1, and N-cadherin, on a
      tissue microarray cohort of 670 breast carcinomas with 30-year follow-up.
      Phaseolus vulgaris leukocytic phytohemagglutinin (LPHA), a lectin specific for
      beta1,6-branched oligosaccharides, was used to assay GnT-V activity. Our results
      show a high degree of correlation of the LPHA staining with matriptase, lamp-1,
      and N-cadherin expressions, but not with epidermal growth factor receptor or
      beta1-integrin expressions. In addition, many of the GnT-V substrate proteins
      exhibited strong coassociations. Elevated levels of GnT-V substrates were
      correlated with various markers of tumor progression, including positive node
      status, large tumor size, estrogen receptor negativity, HER2/neu overexpression,
      and high nuclear grade. Furthermore, LPHA and matriptase showed significant
      association with disease-related survival. Unsupervised hierarchical clustering
      of the GnT-V substrate protein expression and LPHA revealed two distinct
      clusters: one with higher expression of all markers and poor patient outcome and
      one with lower expression and good outcome. These clusters showed independent
      prognostic value for disease-related survival when compared with traditional
      markers of tumor progression. Our results indicate that GnT-V substrate proteins
      represent a unique subset of coexpressed tumor markers associated with aggressive
      disease.

PMID- 16284373
TI  - Interindividual variation in nucleotide excision repair genes and risk of
      endometrial cancer.
AB  - Exposure to estrogens is a likely cause of endometrial cancer, but the means by
      which estrogens exert this effect are not entirely clear. One hypothesis is that
      certain estrogen metabolites bind to the DNA, forming bulky adducts that damage
      the DNA and initiate carcinogenesis. A woman's reduced capacity to repair such
      damage may increase her risk of endometrial cancer. We conducted a population
      based case-control study in western Washington State to address the role of
      variation in nucleotide excision repair genes on the risk of endometrial cancer.
      Case women (n = 371), ages 50 to 69 years, were diagnosed with invasive
      endometrial cancer between 1994 and 1999. Control women (n = 420) were selected
      using random-digit dialing (ages 50-65 years) and by random selection from Health
      Care Financing Administration data files (ages 66-69 years). Genotyping assays
      were done for ERCC1, ERCC2 (XPD), ERCC4 (XPF), ERCC5 (XPG), XPA, and XPC. No
      appreciable differences between cases and controls were observed in the genotype
      distributions of ERCC1 (c8092a and c19007t), ERCC2 (D312N, K751Q, and c22541a),
      ERCC4 (R415Q and t30028c), or ERCC5 (D1104H). Carriage of at least one variant
      allele for XPA G23A was associated with decreased risk of endometrial cancer
      [odds ratio (OR), 0.70; 95% confidence interval (95% CI), 0.53-0.93]. Carriage of
      at least one XPC A499V variant allele was associated with a modest decrease in
      risk (OR, 0.79; 95% CI, 0.59-1.05). Women with variant alleles at both XPC A499V
      and K939Q had 58% of the risk of women with no XPC variant alleles (OR, 0.58; 95%
      CI, 0.35-0.96). Our data suggest that interindividual variation in XPA and XPC
      influences a woman's risk of endometrial cancer.

PMID- 16284374
TI  - Fruit and vegetable consumption and risk of epithelial ovarian cancer: the
      European Prospective Investigation into Cancer and Nutrition.
AB  - OBJECTIVE: The association between consumption of fruit and vegetables and risk
      of ovarian cancer is still unclear from a prospective point of view. METHODS:
      Female participants (n = 325,640) of the European Prospective Investigation into
      Cancer and Nutrition study, free of any cancer at baseline, were followed on
      average for 6.3 years to develop ovarian cancer. During 2,049,346 person-years,
      581 verified cases of primary, invasive epithelial ovarian cancer were accrued.
      Consumption of fruits and vegetables as well as subgroups of vegetables,
      estimated from validated dietary questionnaires and calibrated thereafter, was
      related to ovarian cancer incidence in multivariable hazard regression models.
      Histologic subtype specific analyses were done. RESULTS: Total intake of fruit
      and vegetables, separately or combined, as well as subgroups of vegetables
      (fruiting, root, leafy vegetables, cabbages) was unrelated to risk of ovarian
      cancer. A high intake of garlic/onion vegetables was associated with a borderline
      significant reduced risk of this cancer. The examination by histologic subtype
      indicated some differential effects of fruit and vegetable intake on ovarian
      cancer risk. CONCLUSION: Overall, a high intake of fruits and vegetables did not
      seem to protect from ovarian cancer. Garlic/onion vegetables may exert a
      beneficial effect. The study of the histologic subtype of the tumor warrants
      further investigation.

PMID- 16284375
TI  - Estrogen bioactivation, genetic polymorphisms, and ovarian cancer.
AB  - Recent experimental evidence has shown that catechol estrogens can be activated
      through metabolism to form depurinating DNA adducts and thereby initiate cancer.
      Limited data are available regarding this pathway in epithelial ovarian cancer.
      We conducted a case-control study of 503 incident epithelial ovarian cancer cases
      at the Mayo Clinic in Rochester, MN, and Jacksonville, FL, and a 48-county region
      in North Carolina. Six hundred nine cancer-free controls were frequency matched
      to the cases on age, race, and residence. After an interview to obtain data on
      risk factors, a sample of blood was collected for DNA isolation. Subjects were
      genotyped for seven common single nucleotide polymorphisms in four genes involved
      in catechol estrogen formation (CYP1A1 and CYP1B1) or conjugation (COMT and
      SULT1A1). Data were analyzed using logistic regression, stratified by race, and
      with adjustment for design factors and potential confounders. None of the
      individual genotypes were significantly associated with ovarian cancer risk.
      However, an oligogenic model that considered the joint effects of the four
      candidate genes provided evidence for an association between combinations of
      these genes and ovarian cancer status (P = 0.015). Although preliminary, this
      study provides some support for the hypothesis that low-penetrance susceptibility
      alleles may influence risk of epithelial ovarian cancer.

PMID- 16284376
TI  - Association between quantitative high-risk human papillomavirus DNA load and
      cervical intraepithelial neoplasm risk.
AB  - Human papillomavirus (HPV) infection is a high-risk factor for cervical
      intraepithelial neoplasm (CIN) but the association between the quantitative HPV
      DNA load and the severity of CIN remains controversial. We conducted a community
      study to investigate the correlation between the two. Potential study subjects
      were selected through Pap smear screening in Kaohsiung County, Taiwan. Ninety-one
      subjects with either their first case of inflammation or > or =CIN1 by biopsy
      confirmation were assigned to a case group; 175 normal subjects with negative
      findings by Pap smears or biopsies were assigned to a control group. Cervical HPV
      load was detected with Hybrid Capture II assay for high-risk HPV infection, with
      nested PCR for high- and low-risk HPV infection, and with type-specific PCR for
      HPV type 16 (HPV-16). Individuals with positive high-risk HPV infection had an
      increased risk of developing CIN. Compared with HPV-negative subjects, the odds
      ratios were 32.2 [95% confidence interval (95% CI), 10.4-99.5] for subjects with
      CIN1, 37.2 (95% CI, 7.4-187.6) for subjects with CIN2, and 68.3 (95% CI, 14.1
      328.5) for subjects with > or =CIN3 after adjusting for other confounding
      factors. The similar trend was also found among the HPV-16-negative individuals.
      In addition, high-risk HPV DNA load levels were highly correlated with the
      different grades of CINs in the overall population (Spearman's correlation
      coefficient r = 0.67, P < 0.0001, n = 266) and the HPV-16-negative population
      (Spearman's correlation coefficient r = 0.58, P < 0.0001, n = 234). We concluded
      that high-risk HPV infection, irrespective of HPV-16 infection, was highly and
      positively associated with the development of CIN.

PMID- 16284378
TI  - Fertility among brothers of patients with testicular cancer.
AB  - OBJECTIVE: Patients with testicular cancer have decreased fertility prior to the
      diagnosis of cancer, although it is not clear whether the subfertility is the
      result of an emerging tumor, or whether subfertility and testicular cancer share
      causes. To test if they share causes, we assessed fertility among brothers of
      patients with testicular cancer. METHODS: We compared 5,613 siblings (2,878
      brothers) of patients with germ-cell testicular cancer, diagnosed in Sweden from
      1960 to 2002, with 6,151 population controls (3,202 men). Using the Swedish Multi
      Generation Register, we obtained information on the number of children born
      (until December 2003) from cases (n = 9,480) and controls (n = 10,739). Fertility
      was measured using two indicators, (a) offspring twinning rates, as dizygotic
      twinning is reduced by male subfertility, and (b) number of children. We used
      unconditional logistic regression, and analyzed brothers and sisters separately.
      Analyses on the number of children were restricted to subjects (39%) born prior
      to 1954, for whom information on reproductive life until age 50 was available.
      RESULTS: Brothers, but not sisters, of patients with testicular cancer were less
      likely to have unlike-sex twins than controls (for unlike-sex twins, the odds
      ratio for the father being a sibling of testicular cancer patient was 0.53; 95%
      confidence interval, 0.26-1.09). The likelihood of being a brother of a patient
      with testicular cancer decreased monotonically with increasing number of children
      (P = 0.05), whereas no association was observed for the sisters. CONCLUSION: The
      decreased fertility found among brothers of patients with testicular cancer
      argues in favor of shared causes between cancer-associated subfertility and
      testicular cancer. Genetic links and shared environment could explain the
      association.

PMID- 16284377
TI  - Anal human papillomavirus infection in women and its relationship with cervical
      infection.
AB  - Human papillomavirus (HPV), the primary cause of cervical cancer, is also
      associated with the development of anal cancer. Relatively little is known about
      the epidemiology of anal HPV infection among healthy females and its relationship
      to cervical infection. We sought to characterize anal HPV infection in a cohort
      of adult women in Hawaii. Overall, 27% (372 of 1,378) of women were positive for
      anal HPV DNA at baseline compared with 29% (692 of 2,372) with cervical HPV DNA.
      Among women with paired anal and cervical samples, anal infection without
      accompanying cervical infection was observed in 14% (190 of 1,363). Concurrent
      anal and cervical HPV infections were observed in 13% (178 of 1,363) of women.
      Women with cervical HPV infection had >3-fold increased risk of concurrent anal
      infection. Concurrent anal and cervical HPV infection was most prevalent among
      the youngest women and steadily decreased through age 50 years. By contrast, the
      prevalence of anal infection alone remained relatively steady in all age groups.
      Compared with cervical infections, the overall distribution of HPV genotypes in
      the anus was more heterogeneous and included a greater proportion of nononcogenic
      types. A high degree of genotype-specific concordance was observed among
      concurrent anal and cervical infections, indicating a common source of infection.
      Nevertheless, the association of anal intercourse with anal HPV infection was
      limited to those women without accompanying cervical infection. The relationship
      of anal to cervical infection as described in this study has implications for the
      development of anal malignancies in women.

PMID- 16284379
TI  - The interaction of four genes in the inflammation pathway significantly predicts
      prostate cancer risk.
AB  - It is widely hypothesized that the interactions of multiple genes influence
      individual risk to prostate cancer. However, current efforts at identifying
      prostate cancer risk genes primarily rely on single-gene approaches. In an
      attempt to fill this gap, we carried out a study to explore the joint effect of
      multiple genes in the inflammation pathway on prostate cancer risk. We studied 20
      genes in the Toll-like receptor signaling pathway as well as several cytokines.
      For each of these genes, we selected and genotyped haplotype-tagging single
      nucleotide polymorphisms (SNP) among 1,383 cases and 780 controls from the CAPS
      (CAncer Prostate in Sweden) study population. A total of 57 SNPs were included in
      the final analysis. A data mining method, multifactor dimensionality reduction,
      was used to explore the interaction effects of SNPs on prostate cancer risk.
      Interaction effects were assessed for all possible n SNP combinations, where n =
      2, 3, or 4. For each n SNP combination, the model providing lowest prediction
      error among 100 cross-validations was chosen. The statistical significance levels
      of the best models in each n SNP combination were determined using permutation
      tests. A four-SNP interaction (one SNP each from IL-10, IL-1RN, TIRAP, and TLR5)
      had the lowest prediction error (43.28%, P = 0.019). Our ability to analyze a
      large number of SNPs in a large sample size is one of the first efforts in
      exploring the effect of high-order gene-gene interactions on prostate cancer
      risk, and this is an important contribution to this new and quickly evolving
      field.

PMID- 16284380
TI  - Polymorphisms/haplotypes in DNA repair genes and smoking: a bladder cancer case
      control study.
AB  - Bladder cancer is associated with tobacco smoking and occupational exposure. The
      repair of DNA damage has a key role in protecting the genome from the insults of
      cancer-causing agents. We analyzed 13 polymorphisms in seven DNA repair genes
      belonging to different repair pathways [X-ray repair cross-complementing group 1
      (XRCC1): 26304C>T, 26651A>G, 28152A>G; xeroderma pigmentosum-D (XPD): 23591A>G,
      35931A>C; excision repair complementing defective in Chinese hamster, group 1
      (ERCC1): 19007C>T; XRCC3: 4541T>C, 17893A>G, 18067C>T; proliferating cell nuclear
      antigen (PCNA): 6084G>C; ERCC4: 30028C>T, 30147A>G; and XRCC2-31479A>G] in 317
      incident bladder cancer patients and 317 controls. After adjustment for age and
      smoking, the PCNA-6084C variant was significantly associated with an increased
      risk of bladder cancer [CC + CG versus GG, odds ratio (OR), 1.61; 95% confidence
      interval (95% CI), 1.00-2.61], as well as the XRCC1-26651G variant (GG+AG versus
      AA: OR, 1.73; 95% CI, 1.17-2.56). After stratifying by smoking habits, an
      elevated risk for carriers of the XRCC3-18067T allele was detected both in
      current (TT versus CC: OR, 2.65; 95% CI, 1.21-5.80; CT versus CC: OR, 1.96; 95%
      CI, 1.09-3.52) and never smokers (TT versus CC: OR, 4.34; 95% CI, 1.14-16.46; CT
      versus CC: OR, 2.02; 95% CI, 0.72-5.66), whereas an opposite and slightly weaker
      effect was associated to the XRCC3-17893G allele in current smokers (GG versus
      AA: OR, 0.30; 95%CI, 0.11-0.82; AG versus AA: OR, 0.73; 95% CI, 0.42-1.27).
      XRCC3,XRCC1, ERCC4, and XPD-ERCC1 haplotype frequencies were estimated by the
      maximum likelihood method. The XRCC3-TAT haplotype was associated with an
      enhanced risk in the current smokers group (OR, 1.62; 95% CI, 1.15-2.29), whereas
      a reduction of the risk in the overall sample was observed in the presence of the
      XRCC3-TAC (OR, 0.69; 95% CI, 0.50-0.97). A significant protective effect of the
      XPD-ERCC1-ACC haplotype was observed among never smokers (OR, 0.16; 95% CI, 0.03
      0.81). Our results suggest that polymorphisms and/or haplotypes in XRCC3, XRCC1,
      and PCNA genes and spanning XPD-ERCC1 region may modulate bladder cancer risk and
      that some of these effects may preferentially affect current smokers.

PMID- 16284381
TI  - Adherence assessment using medication weight in a phase IIb clinical trial of
      difluoromethylornithine for the chemoprevention of skin cancer.
AB  - OBJECTIVE: Adherence is a common and essential measurement in clinical trials.
      This study evaluates the association between participant self-reported study
      diary records and the weight of the medication vessel at each study visit, in the
      setting of a phase IIb topical chemoprevention trial. METHODS: One hundred and
      twenty-four eligible participants were randomized to one of four arms [34 to
      difluoromethylornithine (DFMO) plus triamcinolone, 31 to DFMO plus placebo, 31 to
      placebo plus triamcinolone, and 28 to double placebo] for 6 months of treatment
      for actinic keratosis. Adherence was assessed at each clinic visit by weighing
      each tube of dispensed and returned medication and the participant's study diary.
      RESULTS: Self-reported adherence was consistently higher than adherence measured
      by returned medication weight (96.5% versus 71.3%, 94.6% versus 82.4%, 95.3%
      versus 69.5%, and 95.8% versus 66.8% for DFMO, DFMO placebo, triamcinolone, and
      triamcinolone placebo, respectively; P < 0.001). Most participants (59.2%)
      recorded 100% adherence on the study diary; however, using the weight adherence,
      only 10.2% were completely adherent to the study regimen. CONCLUSIONS: Self
      reported diary measures seem to overestimate adherence when compared with
      weighing the returned medication vessel. It is recommended that future clinical
      trials involving topical applications incorporate medication weights as a primary
      measure of adherence because it is objective, quantitative, inexpensive,
      noninvasive, and easy to use.

PMID- 16284382
TI  - Risk of second primary cancer and death following a diagnosis of nonmelanoma skin
      cancer.
AB  - Cancer-free patients diagnosed with a first primary nonmelanoma skin cancer
      (NMSC) offer an opportunity for studying the risk of a second primary cancer
      without the confounding effect of systemic treatment. The objective of the study
      was to estimate the risk of second primary cancer in people with a history of
      basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) and the risk of dying
      in cancer patients with a NMSC history. BCC and SCC cases diagnosed between 1956
      and 2000 in Manitoba, Canada were followed-up for second primaries (other than
      NMSC). Standardized incidence and mortality ratios (SIR and SMR) were calculated.
      Men [SIR, 1.06; 95% confidence interval (95% CI), 1.02-1.10] and women (SIR,
      1.07; 95% CI, 1.02-1.12) with a BCC history as well as men (SIR, 1.15; 95% CI,
      1.08-1.22) with a SCC history were at greater risk of a second primary cancer.
      Overall, the increased risk was observed only in the first 4 years following a
      NMSC, although it remained increased for specific cancer sites. The risk remained
      higher in all age groups up to 75 years of age. People with a history of BCC
      (males: SMR, 1.09; 95% CI, 1.04-1.14; females: SMR, 1.24; 95% CI, 1.16-1.32) or
      SCC (males: SMR, 1.18; 95% CI, 1.09-1.27; females: SMR, 1.55; 95% CI, 1.35-1.79)
      had a greater risk of death following their second primaries. Even if NMSC
      patients are at greater risk of a second cancer, it is not recommended to follow
      them up beyond the generally accepted periodic examination of the skin.

PMID- 16284383
TI  - Explaining the socioeconomic variation in cancer risk in the Norwegian Women and
      Cancer Study.
AB  - Associations between level of education and cancer risk is well supported by
      scientific evidence, but previous studies could only partly adjust for relevant
      confounding factors. In this article, we examined how risk of cancer varies with
      level of education and identified factors that explain this variation using data
      from a prospective cohort study, including 93,638 Norwegian women who responded
      to an extensive questionnaire in 1991/1992 or 1996/1997. A total of 3,259
      incident primary invasive cancer cases were diagnosed during follow-up, which
      ended in December 2001. We used Cox proportional hazards model to calculate
      relative risks (RR) with 95% confidence intervals (95% CI). Besides a similar
      overall risk of female cancers by level of education, we observed differing risks
      between educational groups for cancers of the lung, breast, cervix, kidney, and
      skin melanoma. Women with >16 years of education had an increased risk of breast
      cancer (RR, 1.46; 95% CI, 1.19-1.79) and a decreased risk of lung cancer (RR,
      0.30; 95% CI, 0.13-0.70) and cervical cancer (RR, 0.38; 95% CI, 0.17-0.85)
      compared with the lowest educated women (7-9 years). The middle educated (13-16
      years) had the lowest risk of kidney cancer (RR, 0.24; 95% CI, 0.08-0.71),
      whereas the risk of skin melanoma was highest among women with 10 to 12 years of
      education (RR, 1.53; 95% CI, 1.05-2.24) compared with the lowest educated women.
      After multivariate adjustment for potential confounders related to level of
      education, the variation in cancer risk according to educational levels declined
      into nonsignificance for all these sites.

PMID- 16284384
TI  - The predicted impact of coding single nucleotide polymorphisms database.
AB  - Nonsynonymous single nucleotide polymorphisms (nsSNP) have the potential to
      affect the structure or function of expressed proteins and are, therefore, likely
      to represent modifiers of inherited susceptibility. We have classified and
      catalogued the predicted functionality of nsSNPs in genes relevant to the biology
      of cancer to facilitate sequence-based association studies. Candidate genes were
      identified using targeted search terms and pathways to interrogate the Gene
      Ontology Consortium database, Kyoto Encyclopedia of Genes and Genomes database,
      Iobion's Interaction Explorer PathwayAssist Program, National Center for
      Biotechnology Information Entrez Gene database, and CancerGene database. A total
      of 9,537 validated nsSNPs located within annotated genes were retrieved from
      National Center for Biotechnology Information dbSNP Build 123. Filtering this
      list and linking it to 7,080 candidate genes yielded 3,666 validated nsSNPs with
      minor allele frequencies > or =0.01 in Caucasian populations. The functional
      effect of nsSNPs in genes with a single mRNA transcript was predicted using three
      computational tools-Grantham matrix, Polymorphism Phenotyping, and Sorting
      Intolerant from Tolerant algorithms. The resultant pool of 3,009 fully annotated
      nsSNPs is accessible from the Predicted Impact of Coding SNPs database at
      http://www.icr.ac.uk/cancgen/molgen/MolPopGen_PICS_database.htm. Predicted Impact
      of Coding SNPs is an ongoing project that will continue to curate and release
      data on the putative functionality of coding SNPs.

PMID- 16284386
TI  - Genetic polymorphisms in XRCC1, APE1, ADPRT, XRCC2, and XRCC3 and risk of chronic
      benzene poisoning in a Chinese occupational population.
AB  - DNA damage induced by benzene is an important mechanism of its genotoxicity that
      leads to chronic benzene poisoning (CBP). Therefore, genetic variation in DNA
      repair genes may contribute to susceptibility to CBP in the exposed population.
      Because benzene-induced DNA damage includes single- and double-strand breaks, we
      hypothesized that single-nucleotide polymorphisms in X-ray repair cross
      complementing group 1 (XRCC1), apurinic/apyrimidinic endonuclease (APE1), ADP
      ribosyltransferase (ADPRT), X-ray repair cross-complementing group 2 (XRCC2), and
      X-ray repair cross-complementing group 3 (XRCC3) are associated with risk of CBP.
      We genotyped single-nucleotide polymorphisms at codons 194, 280, and 399 of
      XRCC1, codon 148 of APE1, codon 762 of ADPRT, codon 188 of XRCC2, and codon 241
      of XRCC3 in 152 CBP patients and 152 healthy workers frequency matched on age and
      sex among those who were occupationally exposed to benzene. The genotypes were
      determined by PCR-RFLP technique with genomic DNA. We found that no individuals
      had the XRCC2 codon 188 variant alleles or Met/Met genotype of XRCC3 codon 241 in
      this study population. However, individuals carrying the XRCC1 194Trp allele
      (i.e., Arg/Trp+Trp/Trp genotypes) had a decreased risk of CBP [adjusted odds
      ratio (OR(adj)), 0.60; 95% confidence interval (95% CI), 0.37-0.98; P = 0.041]
      compared with subjects with the Arg/Arg genotype whereas individuals carrying the
      XRCC1 280His allele (i.e., Arg/His+His/His genotypes) had an increased risk of
      CBP compared with those with the Arg/Arg genotype (OR(adj), 1.91; 95% CI, 1.17
      3.10; P = 0.009). The analysis of haplotypes of polymorphisms in XRCC1 showed
      that there was a 2.96-fold (OR, 2.96; 95% CI, 1.60-5.49; chi(2) = 12.39, P =
      0.001) increased risk of CBP for subjects with alleles of XRCC1 194Arg, XRCC1
      280His, and XRCC1 399Arg compared with those carrying alleles of XRCC1 194Arg,
      XRCC1 280Arg, and XRCC1 399Arg. Therefore, our results suggest that polymorphisms
      at codons 194 and 280 of XRCC1 may contribute to CBP in a Chinese occupational
      population.

PMID- 16284385
TI  - Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA
      adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo
      township, Qidong, People's Republic of China.
AB  - Residents of Qidong, People's Republic of China, are at high risk for development
      of hepatocellular carcinoma, in part due to consumption of aflatoxin-contaminated
      foods, and are exposed to high levels of phenanthrene, a sentinel of hydrocarbon
      air toxics. Cruciferous vegetables, such as broccoli, contain anticarcinogens.
      Glucoraphanin, the principal glucosinolate in broccoli sprouts, can be hydrolyzed
      by gut microflora to sulforaphane, a potent inducer of carcinogen detoxication
      enzymes. In a randomized, placebo-controlled chemoprevention trial, we tested
      whether drinking hot water infusions of 3-day-old broccoli sprouts, containing
      defined concentrations of glucosinolates, could alter the disposition of
      aflatoxin and phenanthrene. Two hundred healthy adults drank infusions containing
      either 400 or < 3 micromol glucoraphanin nightly for 2 weeks. Adherence to the
      study protocol was outstanding; no problems with safety or tolerance were noted.
      Urinary levels of aflatoxin-N(7)-guanine were not different between the two
      intervention arms (P = 0.68). However, measurement of urinary levels of
      dithiocarbamates (sulforaphane metabolites) indicated striking interindividual
      differences in bioavailability. An inverse association was observed for excretion
      of dithiocarbamates and aflatoxin-DNA adducts (P = 0.002; R = 0.31) in
      individuals receiving broccoli sprout glucosinolates. Moreover, trans, anti
      phenanthrene tetraol, a metabolite of the combustion product phenanthrene, was
      detected in urine of all participants and showed a robust inverse association
      with dithiocarbamate levels (P = 0.0001; R = 0.39), although again no overall
      difference between intervention arms was observed (P = 0.29). Understanding
      factors influencing glucosinolate hydrolysis and bioavailability will be required
      for optimal use of broccoli sprouts in human interventions.

PMID- 16284387
TI  - Endocrine biomarkers in ductal lavage samples from women at high risk for breast
      cancer.
AB  - BACKGROUND: Ductal lavage is a method of minimal epithelial sampling of the
      breast, with potential utility for repeat sampling and biomarker analysis in
      chemoprevention studies. We report here the baseline findings from a study
      designed to assess the utility of ductal lavage in this setting. METHODS:
      Tamoxifen-eligible, high-risk women underwent ductal lavage; epithelial cell
      number (ECN) and morphology were assessed on Papanicolaou-stained slides.
      Additional slides were immunostained for estrogen receptor (ER) alpha, Ki-67, and
      cyclooxygenase-2, and the labeling index (LI) was established by counting
      negative and positive cells. The ductal lavage supernatant (DLS) was assayed for
      estradiol, several of its precursors, progesterone, cathepsin D, interleukin-6,
      and epidermal growth factor (EGF). RESULTS: One hundred sixty-eight women have
      entered the study (mean age, 51 years; mean 5-year Gail score, 2.8). Ductal
      lavage was accomplished in 145 (86.3%) women. Data were analyzed by duct and by
      woman (averaging data across all ducts). Mild atypia was seen in 43 of 145
      (29.6%), whereas severe atypia was seen in 2 (1.4%) of women. We observed
      significant positive correlations between ECN and cytologic atypia, ER LI,
      cyclooxygenase-2 LI, and Ki-67 LI. EGF levels in supernatant were significantly
      associated with estrogenic precursors, ER LI and ECN. A factor representing the
      DLS hormone and protein variables explained 36% of the variance; total ECN was
      highest when factor score and ER LI were high and was lowest when both were low
      (P for interaction = 0.001). CONCLUSIONS: Biomarker analyses in epithelial cells
      and DLS are feasible. The significant associations of EGF with other markers
      suggest a possible role in increasing epithelial cell mass.

PMID- 16284388
TI  - A multilevel study of socioeconomic predictors of regular mammography use among
      African-American women.
AB  - BACKGROUND: Little is known about the predictors of adherence to mammography
      guidelines by African-American women. We assessed individual-level and group
      level socioeconomic predictors of regular mammography use in a large cohort of
      African-American women. METHODS: We included 14,706 participants in the Black
      Women's Health Study who were 40 to 69 years of age at baseline in 1995. Data
      were obtained through mail questionnaires at entry and biennially during three 2
      year follow-up periods until 2001. We linked the women's addresses to census
      block (neighborhood) socioeconomic data. With multilevel multivariable regression
      analysis, we assessed the relation of individual-level and neighborhood
      socioeconomic factors to "regular" mammography use (use in all three follow-up
      periods) relative to nonregular use, with control for other predictors. RESULTS:
      Most participants had health insurance and almost half had graduated college.
      Having health insurance was the socioeconomic variable most strongly associated
      with regular mammography use (odds ratio, 3.59; 95% confidence interval 3.02
      4.28); the association was present at all levels of educational attainment,
      household income, and neighborhood socioeconomic status. Regular mammography use
      increased with individual household income: odds ratio, 2.00 (95% confidence
      interval, 1.58-2.53) for household income > USD $100,000 relative to < USD
      $15,001. Regular mammography use did not vary across level of education. Higher
      neighborhood socioeconomic status was significantly associated with regular
      mammography use before, but not after, control for household income. CONCLUSIONS:
      Access to health insurance is strongly associated with regular mammography use
      among African-American women, even at higher levels of educational attainment and
      socioeconomic status. Neighborhood socioeconomic characteristics do not
      materially influence regular use.

PMID- 16284389
TI  - Measurements of breast density: no ratio for a ratio.
AB  - Breast density, as visible on mammograms, is generally assessed as the occupied
      percentage of the breast and is a risk factor for breast cancer. Various studies
      have looked into the causation and alteration of relative density but the
      relation of a determinant with a relative measure does not allow a direct
      etiologic interpretation. It was our goal to compare the effects of known
      determinants on relative density and the absolute amounts of dense and nondense
      tissues. We measured the absolute and relative densities in a population of 418
      postmenopausal women participating in a breast cancer screening program. The
      occupied surface area was calculated after manually tracing the contours of the
      tissues on digitized mammograms. Information on determinants was available
      through physical examination and questionnaires. Data were analyzed by
      multivariate linear regression. Age and parity were found to decrease the amount
      of dense tissue and the ages at menarche and menopause were found to increase it
      (R(2) = 13%). The amount of nondense tissue was increased by higher body mass
      index (BMI), age, and parity (R(2) = 43%). Relative density was affected by a
      combination of these factors (R(2) = 29%) with directionalities of effects that
      are comparable to those of dense tissue. However, the magnitudes of these effects
      were the resultant of the effects on dense and nondense tissues. The influence of
      BMI on relative density was completely due to an effect on nondense tissue.
      Although relative density is a relevant prognostic factor, inferences about the
      etiology of breast density should be made on the basis of absolute measures.

PMID- 16284390
TI  - Endogenous sex hormone levels and mammographic density among postmenopausal
      women.
AB  - BACKGROUND: Mammographic density is one of the strongest predictors of breast
      cancer risk. The mechanism by which breast density increases breast cancer risk
      is unclear although it has been hypothesized that breast density reflects
      cumulative exposure to estrogens. METHODS: To evaluate this hypothesis, we
      conducted a cross-sectional study among 520 postmenopausal women in the Nurses'
      Health Study that examined the relation between circulating sex hormones and
      mammographic density. Women were postmenopausal and not taking exogenous hormones
      at the time of blood collection and mammogram. Percent breast density was
      measured from digitized mammograms using a computer-assisted method. Circulating
      estrone, estradiol, androstenedione, testosterone, DHEA, DHEA sulfate, sex
      hormone-binding globulin, progesterone, and prolactin were measured in plasma.
      RESULTS: In contrast to the prior hypothesis, circulating estrogens were
      inversely related to percent mammographic density. The mean percent mammographic
      density was 25.6% among women in the lowest quartile of circulating estradiol
      compared with 14.4% among women in the highest quartile [Spearman correlation (r)
      = -0.22, P < 0.0001]. Circulating estrogens alone explained 1% to 5% of the
      variation of mammographic density. Body mass index was positively associated with
      circulating estradiol levels (r = 0.45, P < 0.0001) and inversely related to
      percent mammographic density (r = -0.51, P < 0.0001). After adjustment for body
      mass index, there was no association between estradiol and breast density (r =
      0.01, P = 0.81). Likewise, there was no relation between the other sex hormones
      measured or prolactin and mammographic density after adjustment for body mass
      index. CONCLUSION: These findings indicate that in postmenopausal women,
      mammographic density is independent of circulating sex hormone levels.

PMID- 16284391
TI  - Pituitary growth hormone and growth hormone-releasing hormone receptor genes and
      associations with mammographic measures and serum growth hormone.
AB  - BACKGROUND: Mammographic density is a strong risk factor for breast cancer that
      is heritable and associated with blood levels of growth hormone and insulin-like
      growth factor-I (IGF-I). We tested single nucleotide polymorphisms (SNP) in
      pituitary growth hormone (GH1) and growth hormone-releasing hormone receptor
      (GHRHR) genes for an association with mammographic density, hormones of the
      growth hormone/IGF-I axis, and anthropometric variables. METHODS: Mammograms from
      348 women were measured using a computer-assisted method, blood collected, and
      DNA extracted. The SNPs genotyped were GH1 -57G>T, GH1 -75G >A, and GHRHR A57T.
      ANOVA and covariance were used to examine associations, adjusted for age, body
      mass index, ethnicity, and menopausal status, between each SNP and three measures
      of the mammogram: percent density, total dense area, and total nondense area.
      Similarly, the SNPs were tested for associations with serum growth hormone, IGF
      I, IGFBP3, prolactin, and anthropometric variables. RESULTS: GH1 -57G >T and GH1 
      75G >A were both associated with percent density and total nondense area. GH1 
      57T homozygotes had 5.2 more mean adjusted percent density than other subjects
      combined (P = 0.03) and 16.2 cm(2) (14.6%) less nondense area (P = 0.01). GH1 
      75A homozygotes had 3.4 more percent density than subjects with at least one G
      allele (P = 0.04) and also had 32% higher serum growth hormone levels (P = 0.02).
      CONCLUSION: We have found associations between mammographic density and two SNPs
      in the pituitary growth hormone gene, one of them also associated with serum
      growth hormone levels. These findings suggest that the GH1 gene may also
      influence breast cancer risk.

PMID- 16284392
TI  - Polymorphisms in the estrogen receptor alpha gene and mammographic density.
AB  - The presence of the PvuII or the XbaI polymorphism in the estrogen receptor alpha
      gene (ESR1, 6q25) has been related to breast cancer risk; however, results are
      not fully consistent. To further elucidate this relation, we examined these
      polymorphisms in relation with mammographic density, a measure of dense tissue in
      the breast, which is strongly associated with breast cancer risk. For this study,
      620 participants aged 49 to 68 years were selected from the Prospect-European
      Prospective Investigation into Cancer and Nutrition cohort. Blood samples,
      lifestyle- and medical questionnaire data and mammograms were available for these
      women. Genotyping was done using the TaqMan PCR assay and mammographic density
      was assessed using a computer-assisted method. Means of mammographic density were
      compared by ESR1 genotypes and haplotypes. The percentage density was higher in
      women with one or two copies of the PvuII p allele (means for Pp and pp are 37%
      and 36%, respectively) than in those with the PP genotype (32%, P(trend) = 0.09).
      Women with one or two copies of the XbaI x allele had higher mean percentage
      density (Xx and xx, 36% and 37%, respectively) than those with the XX genotype
      (31%, P(trend) < 0.01). Haplotype 1 (px) was associated with increased density,
      whereas haplotype 2 (PX) was associated with decreased density, both suggesting
      an allele-dose effect (P(trend) = 0.08 and <0.01, respectively). Similar
      associations were found with absolute density (P(trend) < 0.01). The findings of
      this study support the view that ESR1 polymorphisms may affect breast cancer risk
      through differences in breast density.

PMID- 16284393
TI  - Levels of C-peptide and mammographic breast density.
AB  - Members of the insulin-like growth factor family have been associated with breast
      cancer risk and mammographic breast density, one of the strongest known breast
      cancer risk indicators. The aim of this cross-sectional study was to examine the
      association of levels of C-peptide (a marker of insulin secretion) with
      mammographic breast density among 1,499 healthy women recruited during screening
      mammography examinations. At time of mammography, blood samples and time since
      last meal were collected. Plasma C-peptide levels were measured by ELISA method,
      and mammographic breast density by a computer-assisted method. Spearman's partial
      correlation coefficients, adjusting for age and time since last meal (when
      necessary), were used to evaluate the associations. High body mass index and
      waist-to-hip ratio measurements were independently correlated with high levels of
      C-peptide (r(s) = 0.173 and r(s) = 0.252, respectively; P < 0.0001) or low breast
      density (r(s) = -0.389 and r(s) = -0.142, respectively; P < 0.0001). High levels
      of C-peptide were correlated with low breast density (r(s) = -0.210, P < 0.0001).
      However, the strength of the negative correlation was substantially reduced and
      was no longer significant after further adjustment for body mass index and waist
      to-hip ratio (r(s) = -0.022, P = 0.41). These results suggest that C-peptide
      levels are not associated with breast density after complete adjustment for
      adiposity. Thus, the insulin/C-peptide-breast density relation does not seem to
      mirror the insulin/C-peptide-breast cancer association.

PMID- 16284394
TI  - Evaluating the risk of cervical precancer with a combination of cytologic,
      virologic, and visual methods.
AB  - Several test modalities (cytologic, molecular, and visual) may be used for
      cervical cancer screening, triage, and follow-up. Although no currently available
      single test for cervical neoplasia can detect disease with both high sensitivity
      and specificity, combinations of available tests allow for improved risk
      prediction. We therefore evaluated the combination of liquid-based cytology
      (LBC), human papillomavirus (HPV) DNA testing, and visual inspection
      (cervicography), taken at a single point in time, to predict risk of subsequent
      cervical intraepithelial neoplasia 3 (CIN3) or cancer developing within 2 years
      in a triage population of 5,060 women referred for equivocal or mildly abnormal
      cytology. The concurrent administration of all three test modalities showed that
      combinations of these test modalities permitted clear and distinct risk
      stratification. Among HPV-positive women with high-grade LBC and high-grade
      cervicography results, 79.1 % [95% confidence interval (95% CI), 64.0- 90.0] were
      diagnosed with histologic CIN3 or cancer within 2 years, supporting a "see-and
      treat" clinical application. Conversely, only 1.4% (95% CI, 0.7-2.5) of women
      with a negative HPV, normal cervigram, and second normal cytology result
      developed CIN3 or cancer. Because this low absolute risk was largely attributable
      to the negative HPV test, our results suggest a lack of benefit for a secondary
      or tertiary test result given an HPV-negative test result. Within HPV-positive
      women, however, we observed a steadily increasing absolute risk for cervical
      precancer/cancer with increasing numbers and severity of abnormal test results.
      We conclude that the clear discrimination of cervical cancer risk provided by
      multiple test modalities is consistent with our understanding of cervical
      etiology related to HPV natural history.

PMID- 16284395
TI  - Analysis of total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in smokers'
      blood.
AB  - The sum of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides
      (total NNAL) is an excellent biomarker for uptake of the tobacco-specific
      carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Although numerous
      studies have examined levels of total NNAL in the urine of people who use tobacco
      products, few have quantified this biomarker in blood, and the available methods
      used relatively large amounts of blood. A method is urgently needed for the
      analysis of total NNAL in blood, the fluid most commonly stored in molecular
      epidemiologic studies. We developed a liquid chromatography-electrospray
      ionization-tandem mass spectrometry (LC-ESI-MS/MS) method for the analysis of
      total NNAL in 1-mL samples of plasma. LC-ESI-MS/MS provides both high-sensitivity
      and structural information supporting analyte identity. The method is practical
      and sensitive, with a detection limit of 8 fmol total NNAL/mL plasma. Levels of
      total NNAL averaged 42 +/- 22 (SD) and ranged 1.7 to 88 fmol/mL plasma in 16
      smokers; NNAL was not detected in the plasma of five nonsmokers. These results
      show that total NNAL can readily be quantified in 1-mL plasma samples.

PMID- 16284396
TI  - Variation of the killer cell immunoglobulin-like receptors and HLA-C genes in
      nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is an Epstein-Barrvirus (EBV)-associated
      malignancy. Previous studies have shown that NPC is associated with specific
      human leukocyte antigen (HLA) alleles which function in adaptive immunity to
      present viral and other antigens to the immune system. The role of innate
      immunity in NPC development is unknown. To determine whether innate immunity is
      associated with NPC, a case-control study was conducted among 295 Taiwanese NPC
      cases (99% EBV seropositive) and 252 community controls (29% EBV seropositive).
      Using high-resolution genotyping, we evaluated the variation of HLA class I
      alleles and killer cell immunoglobulin-like receptor (KIR) alleles. Located on
      the surface of natural killer (NK) cells and a subset of T cells, inhibitory KIRs
      diminish NK cytolysis of target cells upon binding to their HLA class I ligands
      and activating KIRs are thought to stimulate NK destruction of target cells. Our
      results suggest that an increasing number of activating KIRs may be associated
      with increasing NPC risk, particularly in individuals seropositive for anti-EBV
      antibodies known to be linked to NPC susceptibility (P(trend) = 0.07). Among EBV
      seropositive individuals, carriers of > or =5 activating KIRs had a 3.4-fold
      increased risk of disease (95% confidence interval, 0.74-15.7) compared with
      individuals with no functional activating KIRs. In contrast, there was no clear
      evidence of risk associated with increasing numbers of inhibitory KIRs. When
      evaluating HLA-Cw alleles, we observed that carriers of HLA-Cw*0401 alleles were
      at a significantly reduced NPC risk (odds ratio, 0.46; 95% confidence intervals,
      0.23-0.92), an effect that could not be explained by linkage disequilibrium with
      other NPC-associated HLA alleles. Our results suggest that KIR-mediated
      activation may be associated with NPC risk. As this finding is consistent with a
      recent report examining cervical cancer, a malignancy caused by human
      papillomavirus, the data raises the possibility that KIRs, and more generally
      innate immunity, may be involved in the pathogenesis of viral-associated cancers.

PMID- 16284397
TI  - Obesity and pancreatic cancer: overall evidence and latency period.

PMID- 16284398
TI  - Talc and anti-MUC1 antibodies.

PMID- 16284399
TI  - Channel properties of TpsB transporter FhaC point to two functional domains with
      a C-terminal protein-conducting pore.
AB  - Integral outer membrane transporters of the Omp85/TpsB superfamily mediate the
      translocation of proteins across, or their integration into, the outer membranes
      of Gram-negative bacteria, chloroplasts, and mitochondria. The Bordetella
      pertussis FhaC/FHA couple serves as a model for the two-partner secretion pathway
      in Gram-negative bacteria, with the TpsB protein, FhaC, being the specific
      transporter of its TpsA partner, FHA, across the outer membrane. In this work, we
      have investigated the structure/function relationship of FhaC by analyzing the
      ion channel properties of the wild type protein and a collection of mutants with
      varied FHA secretion activities. We demonstrated that the channel is formed by
      the C-terminal two-thirds of FhaC most likely folding into a beta-barrel domain
      predicted to be conserved throughout the family. A C-proximal motif that
      represents the family signature appears essential for pore function. The N
      terminal 200 residues of FhaC constitute a functionally distinct domain that
      modulates the pore properties and may participate in FHA recognition.

PMID- 16284400
TI  - Soluble interleukin-15 receptor alpha (IL-15R alpha)-sushi as a selective and
      potent agonist of IL-15 action through IL-15R beta/gamma. Hyperagonist IL-15 x IL
      15R alpha fusion proteins.
AB  - Interleukin-15 (IL-15) is crucial for the generation of multiple lymphocyte
      subsets (natural killer (NK), NK-T cells, and memory CD8 T cells), and
      transpresentation of IL-15 by monocytes and dendritic cells has been suggested to
      be the dominant activating process of these lymphocytes. We have previously shown
      that a natural soluble form of IL-15R alpha chain corresponding to the entire
      extracellular domain of IL-15R alpha behaves as a high affinity IL-15 antagonist.
      In sharp contrast with this finding, we demonstrate in this report that a
      recombinant, soluble sushi domain of IL-15R alpha, which bears most of the
      binding affinity for IL-15, behaves as a potent IL-15 agonist by enhancing its
      binding and biological effects (proliferation and protection from apoptosis)
      through the IL-15R beta/gamma heterodimer, whereas it does not affect IL-15
      binding and function of the tripartite IL-15R alpha/beta/gamma membrane receptor.
      Our results suggest that, if naturally produced, such soluble sushi domains might
      be involved in the IL-15 transpresentation mechanism. Fusion proteins (RLI and
      ILR), in which IL-15 and IL-15R alpha-sushi are attached by a flexible linker,
      are even more potent than the combination of IL-15 plus sIL-15R alpha-sushi.
      After binding to IL-15R beta/gamma, RLI is internalized and induces a biological
      response very similar to the IL-15 high affinity response. Such hyper-IL-15
      fusion proteins appear to constitute potent adjuvants for the expansion of
      lymphocyte subsets.

PMID- 16284401
TI  - Identification of a switch in neurotrophin signaling by selective tyrosine
      phosphorylation.
AB  - Neurotrophins, such as nerve growth factor and brain-derived neurotrophic factor,
      activate Trk receptor tyrosine kinases through receptor dimerization at the cell
      surface followed by autophosphorylation and recruitment of intracellular
      signaling molecules. The intracellular pathways used by neurotrophins share many
      common protein substrates that are used by other receptor tyrosine kinases (RTK),
      such as Shc, Grb2, FRS2, and phospholipase C-gamma. Here we describe a novel RTK
      mechanism that involves a 220-kilodalton membrane tetraspanning protein,
      ARMS/Kidins220, which is rapidly tyrosine phosphorylated in primary neurons after
      neurotrophin treatment. ARMS/Kidins220 undergoes multiple tyrosine
      phosphorylation events and also serine phosphorylation by protein kinase D. We
      have identified a single tyrosine (Tyr(1096)) phosphorylation event in
      ARMS/Kidins220 that plays a critical role in neurotrophin signaling. A
      reassembled complex of ARMS/Kidins220 and CrkL, an upstream component of the C3G
      Rap1-MAP kinase cascade, is SH3-dependent. However, Tyr(1096) phosphorylation
      enables ARMS/Kidins220 to recruit CrkL through its SH2 domain, thereby freeing
      the CrkL SH3 domain to engage C3G for MAP kinase activation in a neurotrophin
      dependent manner. Accordingly, mutation of Tyr(1096) abolished CrkL interaction
      and sustained MAPK kinase activity, a response that is not normally observed in
      other RTKs. Therefore, Trk receptor signaling involves an inducible switch
      mechanism through an unconventional substrate that distinguishes neurotrophin
      action from other growth factor receptors.

PMID- 16284402
TI  - Does the primary school attended influence self-reported health or its risk
      factors in later life? Aberdeen Children of the 1950s Study.
AB  - BACKGROUND: Adult health and its determinants are influenced by the environment
      in childhood. The school attended is known to affect the health behaviours of
      pupils while still at school. Little is known about the long-term influence of
      school attended on health. METHODS: A total of 7,095 respondents (mean age 47
      years) to a follow-up questionnaire who attended primary school in Aberdeen, UK,
      provided information on self-reported health; self-reported high blood pressure;
      GHQ-4; smoking status; alcohol intake; and obesity. Variance partition
      coefficients (VPCs) summarized the variation in adult health outcomes and
      behaviours across schools. Multilevel logistic regression was used to estimate
      the contribution of school to variation in the outcomes taking into account
      individual-level and school-level factors. RESULTS: There was some variation
      across schools in the proportion of adults reporting poor self-rated health (VPC
      = 0.020) and smoking (0.019). Higher VPCs were found for factors potentially
      confounded with school: paternal social classes (I&II) (0.45) and gender (0.44).
      Age at leaving secondary education (0.28) and income (0.10) varied across
      schools. The effects of primary school diminished after adjusting for individual
      level childhood risk factors. The further addition of adult risk factors
      attenuated these childhood effects. After full adjustment there was no effect of
      the primary school attended for high blood pressure, current smoking, alcohol
      intake, and obesity, and negligible effects for the other outcomes. CONCLUSIONS:
      Contrary to our expectations, we found little evidence of any relationship
      between primary school and adult self-reported health or behaviour. This is
      surprising given the extent to which characteristics known to be associated with
      adult health were clustered within schools.

PMID- 16284403
TI  - Commentary: the place in life course research of validated measures of
      socioeconomic position.

PMID- 16284404
TI  - Whose socioeconomic status influences a woman's obesity risk: her mother's, her
      father's, or her own?
AB  - BACKGROUND: Evidence on the relative influence of childhood vs adulthood
      socioeconomic conditions on obesity risk is limited and equivocal. The objective
      of this study was to investigate associations of several indicators of mothers',
      fathers', and own socioeconomic status, and intergenerational social mobility,
      with body mass index (BMI) and weight change in young women. METHODS: This
      population-based cohort study used survey data provided by 8756 women in the
      young cohort (aged 18-23 years at baseline) of the Australian Longitudinal Study
      on Women's Health. In 1996 and 2000, women completed mailed surveys in which they
      reported their height and weight, and their own, mother's, and father's education
      and occupation. RESULTS: Multiple linear regression models showed that both
      childhood and adulthood socioeconomic status were associated with women's BMI and
      weight change, generally in the hypothesized (inverse) direction, but the
      associations varied according to socioeconomic status and weight indicator.
      Social mobility was associated with BMI (based on father's socioeconomic status)
      and weight change (based on mother's socioeconomic status), but results were
      slightly less consistent. CONCLUSIONS: Results suggest lasting effects of
      childhood socioeconomic status on young women's weight status, independent of
      adult socioeconomic status, although the effect may be attenuated among those who
      are upwardly socially mobile. While the mechanisms underlying these associations
      require further investigation, public health strategies aimed at preventing
      obesity may need to target families of low socioeconomic status early in
      children's lives.

PMID- 16284405
TI  - Cause-specific mortality in old age in relation to body mass index in middle age
      and in old age: follow-up of the Whitehall cohort of male civil servants.
AB  - BACKGROUND: The relevance of body mass index (BMI) to cause-specific mortality in
      old age is uncertain. OBJECTIVES: To examine cause-specific 5 year mortality in
      old age by BMI in old age and middle age (40-69 years). METHODS: Cox proportional
      hazards for mortality rates among 4862 former male civil servants in relation to
      quartiles of BMI measured when screened in 1968-70 and when resurveyed in 1997-98
      (median age 76 years). RESULTS: The association between all-cause mortality after
      resurvey and BMI in old age was U-shaped with hazard ratios (HRs) of 1.3 (95% CI
      1.1-1.5) for the lightest and heaviest categories relative to the middle two.
      Among 'healthy' men the lightest (<22.7 kg/m2) had greatest all-cause mortality.
      The heaviest men (>26.6 kg/m2) had increased risk of cardiovascular disease (CVD)
      mortality in the first two years or for the whole period if never-smokers.
      Respiratory mortality was inversely associated with BMI in old age [adjusted HR
      for trend per BMI category increase 0.6 (0.5-0.7)] but cancer mortality lacked a
      clear pattern. Net gain or loss of 10 kg or more between middle and old age was a
      strong predictor of all-cause and CVD mortality. CONCLUSIONS: The shape of the
      association between BMI in old age and mortality differs by cause of death. Major
      weight change over time is a warning signal for higher CVD mortality. Having
      BMI<22.7 kg/m2 in old age is associated with above-average mortality rates even
      if apparently healthy.

PMID- 16284406
TI  - Functional analysis of rice DREB1/CBF-type transcription factors involved in cold
      responsive gene expression in transgenic rice.
AB  - The transcription factors dehydration-responsive element-binding protein 1s
      (DREB1s)/C-repeat-binding factors (CBFs) specifically interact with the DRE/CRT
      cis-acting element and control the expression of many stress-inducible genes in
      Arabidopsis. The genes for DREB1 orthologs, OsDREB1A and OsDREB1B from rice, are
      induced by cold stress, and overexpression of DREB1 or OsDREB1 induced strong
      expression of stress-responsive genes in transgenic Arabidopsis plants, resulting
      in increased tolerance to high-salt and freezing stresses. In this study, we
      generated transgenic rice plants overexpressing the OsDREB1 or DREB1 genes. These
      transgenic rice plants showed not only growth retardation under normal growth
      conditions but also improved tolerance to drought, high-salt and low-temperature
      stresses like the transgenic Arabidopsis plants overexpressing OsDREB1 or DREB1.
      We also detected elevated contents of osmoprotectants such as free proline and
      various soluble sugars in the transgenic rice as in the transgenic Arabidopsis
      plants. We identified target stress-inducible genes of OsDREB1A in the transgenic
      rice using microarray and RNA gel blot analyses. These genes encode proteins that
      are thought to function in stress tolerance in the plants. These results indicate
      that the DREB1/CBF cold-responsive pathway is conserved in rice and the DREB1
      type genes are quite useful for improvement of stress tolerance to environmental
      stresses in various kinds of transgenic plants including rice.

PMID- 16284407
TI  - Physiological and metabolic adaptations of Potamogeton pectinatus L. tubers
      support rapid elongation of stem tissue in the absence of oxygen.
AB  - Tubers of Potamogeton pectinatus L., an aquatic pondweed, over-winter in the
      anoxic sediments of rivers, lakes and marshes. Growth of the pre-formed shoot
      that emerges from the tuber is remarkably tolerant to anoxia, with elongation of
      the stem occurring faster when oxygen is absent. This response, which allows the
      shoot to reach oxygenated waters, occurs despite a 69-81% reduction in the rate
      of ATP production, and it is underpinned by several physiological and metabolic
      adaptations that contribute to efficient energy usage. First, extension of the
      pre-formed shoot is the result of cell expansion, without the accumulation of new
      cellular material. Secondly, after over-wintering, the tuber and pre-formed shoot
      have the enzymes necessary for a rapid fermentative response at the onset of
      growth under anoxia. Thirdly, the incorporation of [(35)S]methionine into protein
      is greatly reduced under anoxia. The majority of the anoxically synthesized
      proteins differ from those in aerobically grown tissue, implying an extensive
      redirection of protein synthesis under anoxia. Finally, anoxia-induced
      cytoplasmic acidosis is prevented to an unprecedented degree. The adaptations of
      this anoxia-tolerant plant tissue emphasize the importance of the mechanisms that
      balance ATP production and consumption in the absence of oxygen.

PMID- 16284411
TI  - The impact of neuroinformatics.

PMID- 16284408
TI  - Leaf yellowing and anthocyanin accumulation are two genetically independent
      strategies in response to nitrogen limitation in Arabidopsis thaliana.
AB  - For the first time in Arabidopsis thaliana, this work proposes the identification
      of quantitative trait loci (QTLs) associated with leaf senescence and stress
      response symptoms such as yellowing and anthocyanin-associated redness. When
      Arabidopsis plants were cultivated under low nitrogen conditions, we observed
      that both yellowing of the old leaves of the rosette and whole rosette redness
      were promoted. Leaf yellowing is a senescence symptom related to chlorophyll
      breakdown. Redness is a symptom of anthocyanin accumulation related to whole
      plant ageing and nutrient limitation. In this work, Arabidopsis is used as a
      model system to dissect the genetic variation of these parameters by QTL mapping
      in the 415 recombinant inbred lines of the Bay-0xShahdara population. Fifteen new
      QTLs and two epistatic interactions were described in this study. The yellowing
      of the rosette, estimated by visual notation and image processing, was controlled
      by four and five QTLs, respectively. The visual estimation of redness allowed us
      to detect six QTLs among which the major one explained 33% of the total
      variation. Two main QTLs were confirmed in near-isogenic lines (heterogenous
      inbred family; HIF), thus confirming the relevance of the visual notation of
      these traits. Co-localizations between QTLs for leaf yellowing, redness and
      nitrogen use efficiency described in a previous publication indicate complex
      interconnected pathways involved in both nitrogen management and senescence- and
      stress-related processes. No co-localization between QTLs for leaf yellowing and
      redness has been found, suggesting that the two characters are genetically
      independent.

PMID- 16284412
TI  - The cerefy brain atlases: continuous enhancement of the electronic talairach
      tournoux brain atlas.
AB  - The Talairach-Tournoux (TT) atlas is probably the most often used brain atlas. We
      overview briefly the activities in developments of electronic versions of the TT
      atlas and focus on our more than 10-yr efforts in its continuous enhancement
      resulting in three main versions: TT-1997, TT-2000, and TT-2004. The recent TT
      2004 version is substantially improved over the digitized print original with a
      higher structure parcellation, better quality and resolution of individual
      structures, and improved three-dimensional (3D) spatial consistency. It is also
      much more suitable for developing atlas-based applications owing to pure color
      coding (for automatic structure labeling), contour representation (to avoid scan
      blocking by the overlaid atlas), and color cross-atlas consistency (for the
      simultaneous use of multiple atlases). We also provide a procedure for 3D spatial
      consistency improvement and illustrate its use. Finally, we present some of our
      latest atlas-assisted applications for fast and automatic interpretation of
      morphological, stroke, and molecular images, and discuss the future steps in TT
      atlas enhancement.

PMID- 16284413
TI  - Phase synchronization measurements using electroencephalographic recordings: what
      can we really say about neuronal synchrony?
AB  - Phase synchrony analysis is a relatively new concept that is being increasingly
      used on neurophysiological data obtained through different methodologies. It is
      currently believed that phase synchrony is an important signature of information
      binding between distant sites of the brain, especially during cognitive tasks.
      Electroencephalographic (EEG) recordings are the most widely used recording
      technique for recording brain signals and assessing phase synchrony patterns. In
      this study, we address the suitability of phase synchrony analysis in EEG
      recordings. Using geometrical arguments and numerical examples, employing EEG and
      magnetoencephalographic data, we show that the presence of a common reference
      signal in the case of EEG recordings results in a distortion of the synchrony
      values observed, in that the amplitudes of the signals influence the synchrony
      measured, and in general destroys the intended physical interpretation of phase
      synchrony.

PMID- 16284414
TI  - Dangerous phase.
AB  - "Use a quiet reference." How many times have we heard this mantra during training
      or practice, interpreting electroencephalogram (EEG) tracings, or implanting
      intracranial electrodes? How many of us have used common reference EEG for
      synchrony studies in recent years? Far too many.Perhaps one source of this
      problem is the number 104. This is the relatively small number of citations to
      the reference Fein et al. (1988), which should have put to rest any further use
      of referential EEG for coherence measurements. And in retrospect, a more careful
      reading by us of Nunez's (1981) text would have instructed us not to do this. How
      such warnings have managed to escape integration into common knowledge and
      practice is troublesome. Electrical potentials are all measured with respect to
      other potentials. Technically, a potential difference is calculated by
      integrating the electrical field over a given path from one place to another in
      EEG terms, we mea sure a potential with respect to another potential, measured at
      one or more electrodes. All EEG potential measurements reflect the paths used to
      measure those potentials, and do not directly reflect localized regions of the
      brain beneath one electrode. Worse, in scalp EEG, the layers of cerebrospinal
      fluid, dura, skull, and scalp serve to smooth, filter, spread out, and redirect
      currents generated within the brain so that the measured scalp potentials bear a
      rather tenuous relationship to the underlying (presumably dipole) current
      sources. In calculating coherence, it is easy to show that if the potential
      differences are all made with respect to a common reference, then the amplitude
      of the reference can dominate the coherence estimate (Fein et al., 1988). In
      recent years, phase synchronization has been increasingly applied to analyze the
      dynamics of nonlinear systems (Pikovsky et al., 2000). In Guevara et al. (in this
      issue), we see the extension of Fein's results for phase coherency. The geometry
      of Fig. 1 in Guevara et al. should be imprinted on all of us the amplitude of a
      common reference can dominate the calculated phase syn chronization. There is far
      too much literature within the past decade that calculated phase synchronization
      from common referenced EEG. The good news is that the fix to remove common
      reference artifacts is simple. The bad news is that the interpretation of
      reference- free synchronization results from brain signals requires considerable
      caution.

PMID- 16284415
TI  - A wavelet-based statistical analysis of FMRI data: I. motivation and data
      distribution modeling.
AB  - We propose a new method for statistical analysis of functional magnetic resonance
      imaging (fMRI) data. The discrete wavelet transformation is employed as a tool
      for efficient and robust signal representation. We use structural magnetic
      resonance imaging (MRI) and fMRI to empirically estimate the distribution of the
      wavelet coefficients of the data both across individuals and spatial locations.
      An anatomical subvolume probabilistic atlas is used to tessellate the structural
      and functional signals into smaller regions each of which is processed
      separately. A frequency-adaptive wavelet shrinkage scheme is employed to obtain
      essentially optimal estimations of the signals in the wavelet space. The
      empirical distributions of the signals on all the regions are computed in a
      compressed wavelet space. These are modeled by heavy-tail distributions because
      their histograms exhibit slower tail decay than the Gaussian. We discovered that
      the Cauchy, Bessel K Forms, and Pareto distributions provide the most accurate
      asymptotic models for the distribution of the wavelet coefficients of the data.
      Finally, we propose a new model for statistical analysis of functional MRI data
      using this atlas-based wavelet space representation. In the second part of our
      investigation, we will apply this technique to analyze a large fMRI dataset
      involving repeated presentation of sensory-motor response stimuli in young,
      elderly, and demented subjects.

PMID- 16284416
TI  - A cross-platform freeware tool for digital reconstruction of neuronal
      arborizations from image stacks.
AB  - Digital reconstruction of neuronal arborizations is an important step in the
      quantitative investigation of cellular neuroanatomy. In this process, neurites
      imaged by microscopy are semi-manually traced through the use of specialized
      computer software and represented as binary trees of branching cylinders (or
      truncated cones). Such form of the reconstruction files is efficient and
      parsimonious, and allows extensive morphometric analysis as well as the
      implementation of biophysical models of electrophysiology. Here, we describe
      Neuron_ Morpho, a plugin for the popular Java application ImageJ that mediates
      the digital reconstruction of neurons from image stacks. Both the executable and
      code of Neuron_ Morpho are freely distributed (www.maths.
      soton.ac.uk/staff/D'Alessandro/morpho or www.krasnow.gmu.edu/L-Neuron), and are
      compatible with all major computer platforms (including Windows, Mac, and Linux).
      We tested Neuron_Morpho by reconstructing two neurons from each of the two
      preparations representing different brain areas (hippocampus and cerebellum),
      neuritic type (pyramidal cell dendrites and olivar axonal projection terminals),
      and labeling method (rapid Golgi impregnation and anterograde dextran amine), and
      quantitatively comparing the resulting morphologies to those of the same cells
      reconstructed with the standard commercial system, Neurolucida. None of the
      numerous morphometric measures that were analyzed displayed any significant or
      systematic difference between the two reconstructing systems.

PMID- 16284417
TI  - Opposite roles of the dmd gene in the control of RNase E and RNase LS activities.
AB  - When the dmd gene of bacteriophage T4 is defective, expression of middle genes
      starts normally but drops abruptly. However, the residual expression of middle
      genes at late stages continues at a higher rate in cells infected with a dmd
      mutant than with the wild type. In order to understand the complex effects of the
      dmd gene, we followed changes in the quantity of mRNA from a middle gene, uvsY.
      The uvsY mRNA was degraded rapidly by RNase LS at middle stages but stabilized at
      late stages, suggesting that RNase LS targets middle-gene mRNAs only at middle
      stages. Furthermore, another RNase targeting middle mRNAs at late stages is also
      suggested to be inactivated when dmd is mutated. We found that RNase E was
      involved in the degradation of uvsY mRNA. Judging from the processing of gene-32
      mRNA, RNase E activity declines after the beginning of the middle stage when dmd
      is defective.

PMID- 16284418
TI  - Genomic relationships among Nicotiana species with different ploidy levels
      revealed by 5S rDNA spacer sequences and FISH/GISH.
AB  - We used the intergenic spacer sequences of the 5S ribosomal RNA genes (5S rDNA)
      to obtain insights into the genomic origin of putative amphidiploid/tetraploid
      species with 2n = 48 and their descendants in Nicotiana. Amplification of the
      spacer sequences and subsequent multiple alignment using the consensus sequences
      from each species, showed that two Australian species shared common large
      deletions, suggesting that the origin of the 5S rDNA is closely related in these
      species. Comparison of the spacer sequences with those from diploid (2n = 24)
      Nicotiana species made it possible to detect some groups consisting of the
      sequences from the 2n = 24 and 2n = 48 level species. Chromosomal localizations
      of the 5S rDNA arrays were similar in most groups. The relationships suggested by
      the 5S rDNA were also assessed at the genome level by using genomic in situ
      hybridization. We showed that the grouping based on the 5S rDNA spacer sequence
      reflects high genomic homology between 2n = 24 and 2n = 48 level species. As a
      result, the putative polyploid species such as N. debneyi, N. quadrivalvis, and
      N. africana were suggested to involve the close relatives of the diploid species
      such as N. glauca, N. obtusifolia and N. sylvestris, and N. langsdorffii,
      respectively, in their speciation. Our results are generally in agreement with
      the relationships previously suggested by morphological and cytogenetic
      observations, and some novel relationships were also revealed.

PMID- 16284419
TI  - Members of TALE and WUS subfamilies of homeodomain proteins with potentially
      important functions in development form dimers within each subfamily in rice.
AB  - Transacting factors often form homo- and heterodimers and regulate various
      targets, the type of regulation depending on the dimeric combination. The WUS and
      TALE subfamilies are two atypical homeodomains in plants. A homeodomain mediates
      sequence-specific binding to its target DNA and usually consists of 60 amino acid
      residues, whereas atypical homeodomains have extra amino acid residues in the
      well-conserved region. The genes OsWUS and OsPRS, which encode atypical
      homeodomain proteins from the WUS subfamily, and OsBEL and OSH15, which encode
      those from the TALE subfamily, were isolated from rice and tested for their
      interactions by yeast two-hybrid analysis. OsWUS and OsPRS formed homodimers and
      formed heterodimers with each other but did not form dimers with the TALE family
      homeodomain proteins OSH15 or OsBEL. Likewise, OSH15 and OsBEL formed homodimers
      and heterodimers but did not form dimers with the WUS family homeodomain proteins
      OsWUS and OsPRS. These findings suggest that the combinations of dimers are well
      correlated with the classification of these proteins on the basis of sequence
      similarity. RT-PCR analysis revealed that expression of OsWUS and OsPRS was
      detected in the same organs, namely floral buds, roots, and suspension cells.
      Therefore, it is possible that the proteins encoded by both of these genes
      function as homo- and heterodimers in planta. These results suggest that, during
      the evolution of these subfamilies, various combinations of dimers within
      proteins encoded by paralogous genes were formed and generated independent
      regulatory networks that enabled complex patterns of plant development.

PMID- 16284420
TI  - Comprehensive analysis of dynamics of histone H4 acetylation in mitotic barley
      cells.
AB  - Nucleosomal histones are covalently modified at specific amino acid residues. In
      the case of histone H4, four lysines (K5, K8, K12, and K16) are acetylated. In
      the current studies, we examined the dynamics of histone H4 acetylation at K8 and
      K12 in mitotic barley cells using a three-dimensional immunofluorescent method.
      Based on the results and previous studies on the dynamics of K5 and K16
      acetylation, we provide a comprehensive view of the dynamics of H4 acetylation.
      Interphase nuclei exhibit strong acetylation in the centromeric region at K5, K8
      and K12. In the case of K12, strong acetylation at nucleolar organizing regions
      was observed from prophase to anaphase. The dynamics of K12 were closely related
      to those of K5. On the other hand, K8 exhibited a pattern of almost uniform
      acetylation from prophase to telophase and strong acetylation in distal regions
      of chromosomes at both metaphase and anaphase, which is very similar to the
      dynamics of K16 acetylation. Thus, it appears that there is pair-wise acetylation
      of K12 and K5 in the nucleolar organizing regions and of K8 and K16 in the gene
      rich regions. Together, these results suggest that pair-wise dynamics of H4
      acetylation regulate chromosomal structure and function during the cell cycle.

PMID- 16284421
TI  - Variations in a hotspot region of chloroplast DNAs among common wheat and
      Aegilops revealed by nucleotide sequence analysis.
AB  - The second largest BamHI fragment (B2) of the chloroplast DNA in Triticum (wheat)
      and Aegilops contains a highly variable region (a hotspot), resulting in four
      types of B2 of different size, i.e. B2l (10.5kb), B2m (10.2kb), B2 (9.6kb) and
      B2s (9.4kb). In order to gain a better understanding of the molecular nature of
      the variations in length and explain unexpected identity among B2 of Ae. ovata,
      Ae. speltoides and common wheat (T. aestivum), the nucleotide sequence between a
      stop codon of rbcL and a HindIII site in cemA in the hotspot was determined for
      Ae. ovata, Ae. speltoides, Ae. caudata and Ae. mutica. The total number of
      nucleotides in the region was 2808, 2810, 3302, and 3594 bp, for Ae. speltoides,
      Ae. ovata, Ae. caudata and Ae. mutica, respectively, and the sequences were
      compared with the corresponding ones of Ae. crassa 4x, T. aestivum and Ae.
      squarrosa. Compared with the largest B2l fragment of Ae. mutica, a 791bp and a
      793 bp deletion were found in Ae. speltoides and Ae. ovata, respectively, and the
      possible site of deletion in the two species is the same as that of T. aestivum.
      However, a deleted segment in Ae. ovata is 2 bp longer than that of Ae.
      speltoides (and T. aestivum), demonstrating that recurrent deletions had occurred
      in the chloroplast genomes of both species. Comparison of the sequences from Ae.
      caudata and Ae. crassa 4x with that of Ae. mutica revealed a 289 bp and a 61 bp
      deletion at the same site in Ae. caudata and Ae. crassa 4x, respectively.
      Sequence comparison using wild Aegilops plants showed that the large length
      variations in a hotspot are fixed to each species. A considerable number of
      polymorphisms are observed in a loop in the 3' of rbcL. The study reveals the
      relative importance of the large and small indels and minute inversions to
      account for variations in the chloroplast genomes among closely related species.

PMID- 16284422
TI  - Effect of population structure on the amount of polymorphism and the fixation
      probability under overdominant selection.
AB  - Under overdominant selection, mutants substantially contribute to increase the
      amount of polymorphism. It is also known that under neutrality as the migration
      rates among demes decrease in a subdivided population, the amount of polymorphism
      increases along with the increase of the effective population size, N(e). In this
      study, under overdominant selection the effect of population subdivision on the
      amount of polymorphism was investigated using the diffusion approximation and the
      low migration approximation. It was shown that if selection is medium or strong
      (e.g., N(T)s > 1, where N(T) is the population size and s is the selective
      advantage of heterozygotes), the nucleotide diversity, pi, decreases along with
      the decrease of Nm against the increase of N(e), where N is the size of demes and
      m is the migration rate per deme. In addition, the ratio of the nucleotide
      diversity to the evolutionary rate also decreases along with the decrease of Nm.
      In some cases the ratio becomes smaller than that expected under neutrality as Nm
      decreases.

PMID- 16284423
TI  - Nonsynonymous site heteroplasmy in fish mitochondrial DNA.
AB  - Heteroplasmic nucleotide polymorphisms are rarely observed in wild animal
      mitochondrial DNA. The occurrence of such site heteroplasmy is expected to be
      extremely rare at nonsynonymous sites where the number of nucleotide
      substitutions per site is low due to functional constraints. This report deals
      with nonsynonymous mitochondrial heteroplasmy from two wild fish species, chum
      salmon and Japanese flounder. We detected an A/C nonsynonymous heteroplasmic site
      corresponding to putative amino acids, Ile or Met, in NADH dehydrogenase subunit
      5 (ND5) region of chum salmon. The heteroplasmic site was at the 3rd position of
      58th codon. As for Japanese flounder we detected a C/T nonsynonymous
      heteroplasmic site corresponding to putative amino acids, Leu or Pro, in ND4
      region. The heteroplasmic site was at the 2nd position of 450th codon. We also
      verified heteroplasmy at these sites by sequencing cloned fragments.

PMID- 16284424
TI  - Polymorphisms of the prion protein gene (PRNP) in Hanwoo (Bos taurus coreanae)
      and Holstein cattle.
AB  - Polymorphisms in the prion protein gene (PRNP) in humans and sheep correlate with
      susceptibility to transmissible spongiform encephalopathies (TSEs). Bovine
      spongiform encephalopathy (BSE) has been reported in British and Japanese cattle;
      it has occurred thus far in Holstein cattle. BSE in Hanwoo (Bos taurus coreanae)
      cattle has not been diagnosed up to now. To characterize the bovine PRNP
      polymorphisms in Korean cattle, we analyzed the open reading frame (ORF) of PRNP
      in 120 Hanwoo (beef) cattle and 53 Holstein (dairy) cattle. Three polymorphisms
      were found, the third position of codon 78 (G-->A), the third position of codon
      192 (C-->T), and the deletion of a single octa-repeat. An analysis of codon 78
      revealed no difference in the genotype (P = 0.2026) or allele (P = 0.7180)
      frequencies between Hanwoo and Holstein animals. However, there were significant
      differences in the genotype (P < 0.0001) and allele (P < 0.0001) frequencies at
      PRNP codon 192 between Hanwoo and Holstein animals. The rate of Holstein animals
      with deletion of a single octa-repeat was 91.5% undeleted homozygotes, 8.5%
      heterozygotes (with R3 deletion), and 0% deleted homozygotes. However, none of
      the 120 Hanwoo animals had any octa-repeat deletions. The genotype (P < 0.0001)
      and allele (P < 0.0001) frequencies of a single octa-repeat-deletion were also
      significantly different between Hanwoo and Holstein animals.

PMID- 16284425
TI  - Assays for thyroid-stimulating antibodies and thyrotropin-binding inhibitory
      immunoglobulins in children with Graves' disease.
AB  - Studies on thyrotropin receptor autoantibodies (TRAb) by measurement of both
      thyroid-stimulating antibodies (TSAb) and thyrotropin-binding inhibitory
      immunoglobulins (TBII) in serum from children with Graves' disease are limited in
      number of studies. The aim of this study was to investigate the levels of serum
      TSAb and TBII in children with Graves' disease, and to evaluate the clinical
      significance of these antibodies. We measured the serum TSAb and TBII at
      diagnosis and during management in 65 children with Graves' disease. Patients
      were divided into four groups according to their metabolic state: those with
      untreated active Graves' disease, those receiving treatment with antithyroid
      drugs, those in remission, and those in relapse. At diagnosis, both TSAb and TBII
      assays had high sensitivities and high specificities. In follow-up, the levels of
      both TSAb and TBII paralleled the course of the disease. There was a strong
      positive correlation between TSAb and TBII. TBII levels were significantly higher
      in the patients with ophthalmopathy than those without ophthalmopathy in
      untreated Graves' children. It was concluded that TSAb and TBII measurements are
      valuable in the diagnosis and management of children with Graves' disease.

PMID- 16284426
TI  - A case of hyperinsulinemia of undetermined origin, successfully treated with long
      acting octreotide.
AB  - Major causes of fasting hypoglycemia in adults are insulinoma, factitious
      hypoglycemia and nesidioblastosis. The primary treatment for insulinoma is
      surgical removal of the tumor, but there are cases with hyperinsulinemia that
      cannot undergo surgery. Somatostatin analogue is one of the treatments used in
      such cases of insulinoma or persistent hyperinsulinemic hypoglycemia. We report
      here a patient who had undetermined hyperinsulinemia and was successfully treated
      with a long-acting somatostatin analogue, which had recently become available.
      The patient, a 72-year-old female, who had previously been diagnosed as
      insulinoma and undergone partial pancreatectomy, was admitted complaining of the
      recurrence of hypoglycemic attacks after an interval of ten years. On admission,
      hypoglycemia (42 mg/dl), hyperinsulinemia (IRI: 79.3 microU/m) and low HbA1c
      (3.6%) were present. In 75 g-OGTT at 30 min after load, IRI reached 6623
      microU/ml, while plasma glucose level was 88 mg/dl. The anti-insulin antibody was
      not present. Since attempts at tumor localization by imaging techniques failed
      and the patient refused further examinations or surgical treatment, we
      recommended her to take a medication with a somatostatin analogue. Insulin
      suppression test using 50 microg of octreotide improved plasma glucose and IRI
      levels, suggesting the usefulness of the treatment, and a monthly administration
      of 20 mg of long-acting octreotide has successfully controlled her symptoms of
      hypoglycemia for 10 months. Our case demonstrated the utility of the long-acting
      somatostatin analogue for long-term treatment of undetermined hyperinsulinemia. A
      preliminary loading test using short-acting octreotide may be useful to determine
      appropriate medication, especially in cases who cannot receive surgical
      treatment.

PMID- 16284427
TI  - Serum adiponectin, resistin levels and non-alcoholic fatty liver disease in obese
      children.
AB  - The objective is to investigate the relation between the levels of two serum
      adipocytokines (adiponectin and resistin) and non-alcoholic fatty liver disease
      (NAFLD) in obese children. In this study, 113 obese children were enrolled and
      divided into 3 groups. Obese group 1 was defined as obese children without any
      liver abnormality. Obese group 2 was defined as obese children just with fatty
      infiltration of the liver in ultrasonic appearance and obese group 3 was defined
      as obese children with liver function abnormality. The controls consisted of 37
      nonobese children without endocrine, metabolic or kidney disease. The levels of
      serum adiponectin and resistin were measured by ELISA method. Insulin resistance
      by homeostasis model (HOMA-IR), area under curve of glucose (AUCG), serum total
      cholesterol, triglyceride, alanine aminotransferase, uric acid, HDL-cholesterol,
      LDL-cholesterol and body mass index (BMI) were measured as well. In obese
      children, NAFLD were found in 63 cases (55.75%). Serum adiponectin levels of
      obese children were significantly lower than that of controls (3.63 vs 5.79
      microg/mL, P<0.001) while serum resistin levels were not different (P = 0.876).
      Moreover, serum adiponectin levels in obese group 1 were significantly higher
      than that of group 2 and 3 (4.24 vs 3.37 and 3.12 microg/mL, all P<0.05) and no
      difference was found between obese group 2 and obese group 3 (P>0.05). Serum
      resistin levels among the three obese groups were 4.37 ng/mL, 3.72 ng/mL and 4.24
      ng/mL without significant difference (P = 0.592). NAFLD, BMI, gender and HDL
      cholesterol were independent determinants of serum adiponectin levels in children
      analyzed by multiple regression analysis, which explained 33% of the variance.
      Serum adiponectin levels were inversely associated with BMI, gender and NAFLD
      (all P<0.05) and were positively associated with HDL-cholesterol levels (P =
      0.033). These results suggest that adiponectin might be a protective factor in
      NAFLD occurrence in obese children, and that the measurement of adiponectin
      should be part of the standard evaluation of the obese child and may help to
      evaluate the occurrence of NAFLD.

PMID- 16284428
TI  - Clinical evaluation of 3rd generation assay for thyrotropin receptor antibodies:
      the M22-biotin-based ELISA initiated by Smith.
AB  - Recently a new procedure for measuring serum TSH receptor (TSHR) autoantibody
      (TRAb) was reported by Smith et al. in which the autoantibodies inhibit binding
      of a human monoclonal thyroid stimulating antibody M22 (labeled with biotin) to
      TSHR-coated ELISA plate wells (pTRAb(3rd) assay). The aim of this study was to
      compare the performance of pTRAb(3rd) assay with pTRAb(2nd) assay based on
      inhibition of TSH-biotin binding to TSHR-coated ELISA plate wells. In addition,
      we evaluated the applicability of TRAb3rd assay to discriminate between untreated
      Graves' disease (GD) and painless thyroiditis (PT). Analysis of sera from 230
      healthy controls indicated that only 1 (0.43%) gave inhibition of M22-binding
      values of greater than 15% (32.8% inhibition). To define the clinical cut-off
      point for a positive serum with autoantibodies to the TSHR, we performed receiver
      operating characteristic curve of the data from 244 untreated GD and three
      different control groups for pTRAb(3rd) assay. With a sensitivity of 99.6% at a
      cut-off of 14.5%, 22.0% and 22.0% inhibition of M22 binding, the specificity of
      healthy controls without PT, with PT and with PT excluding postpartum PT and PT
      during remission of GD was 99.6%, 96.6% and 97.5%, respectively. The pTRAb(3rd)
      assay was closely correlated to pTRAb(2nd) assay in the 244 untreated Graves'
      sera (r = 0.911). The pTRAb(3rd) assay detected 243 of 244 (99.6%) untreated GD,
      whereas 9.2% of PT and 6.7% of the subacute thyroiditis (SAT) were detectable. In
      contrast, pTRAb (2nd) assay detected 242 of 244 (99.2%) Graves' same sera, while
      16.8 % from PT's same sera and 13.3% from SAT were detectable. In conclusion,
      pTRAb(3rd) assay has significantly (p = 0.0026) superior diagnostic accuracy for
      GD and PT, compared to that of pTRAb(2nd) assay.

PMID- 16284429
TI  - The effect of defective early phase insulin secretion on postload glucose
      intolerance in impaired fasting glucose.
AB  - Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are two risk
      groups for type 2 diabetes. Type 2 diabetes is characterized by both impaired
      insulin secretion and insulin resistance but their relative contribution to the
      development of hyperglycemia may differ due to heterogeneity of the disease.
      Combined glucose intolerance (CGI), on the other hand, seems to represent a more
      advanced stage of prediabetes that bears a distinctly higher risk of progression
      to diabetes and its comorbidities. This study has the aim to compare isolated IFG
      and CGI categories with respect to the degree of early phase insulin secretion
      abnormalities and insulin resistance. Subjects who had IFG (fasting glucose: 110
      126 mg/dl) were included in the study. A 75-g oral glucose tolerance test (OGTT)
      with insulin response was done and subjects were classified according to the WHO
      criteria. Six subjects were excluded because they had diabetic glucose tolerance.
      A total of 66 patients (53.4 +/- 11.1 years, female/male: 48/18) were divided
      into two groups according to their glucose tolerance in OGGT (Group 1: isolated
      IFG and group 2: CGI). Early phase insulin secretion was measured by intravenous
      glucose tolerance test (IVGTT) and OGTT. Insulin resistance was assessed by the R
      value of the homeostasis model assessment (HOMA). We did not find any
      statistically significant difference between groups according to age, gender,
      body mass index (BMI), fasting glucose, fasting insulin, insulin-AUC (0-180 min)
      and HOMA-R values. In OGGT there was no statistically significant difference
      between 0', 30', 60' and 90' insulin levels of the groups; only 120' and 180'
      insulin levels were higher in CGI than in IFG group (p<0.05). In IVGTT, there was
      no statistically significant difference between glucose levels of the groups.
      Furthermore, insulin response to intravenous glucose was higher in IFG than in
      CGI (p<0.05). Our data demonstrate that isolated IFG and CGI are similar with
      respect to the degree of insulin resistance, and that subjects with CGI had a
      more prominent deficit in early phases of insulin secretion.

PMID- 16284430
TI  - Ratio of serum free triiodothyronine to free thyroxine in Graves' hyperthyroidism
      and thyrotoxicosis caused by painless thyroiditis.
AB  - The serum T3 to T4 ratio is a useful indicator for differentiating destruction
      induced thyrotoxicosis from Graves' thyrotoxicosis. However, the usefulness of
      the serum free T3 (FT3) to free T4 (FT4) ratio is controversial. We therefore
      systematically evaluated the usefulness of this ratio, based on measurements made
      using two widely available commercial kits in two hospitals. Eighty-two untreated
      patients with thyrotoxicosis (48 patients with Graves' disease and 34 patients
      with painless thyroiditis) were examined in Kuma Hospital, and 218 patients (126
      with Graves' disease and 92 with painless thyroiditis) and 66 normal controls
      were examined in Ito Hospital. The FT3 and FT4 values, as well as the FT3/FT4
      ratios, were significantly higher in the patients with Graves' disease than in
      those with painless thyroiditis in both hospitals, but considerable overlap
      between the two disorders was observed. Receiver operating characteristic (ROC)
      curves for the FT3 and FT4 values and the FT3/FT4 ratios of patients with Graves'
      disease and those with painless thyroiditis seen in both hospitals were prepared,
      and the area under the curves (AUC), the cut-off points for discriminating
      Graves' disease from painless thyroiditis, the sensitivity, and the specificity
      were calculated. AUC and sensitivity of the FT(3)/FT(4) ratio were smaller than
      those of FT(3) and FT(4) in both hospitals. The patients treated at Ito hospital
      were then divided into 4 groups according to their FT4 levels (A: < or =2.3, B:
      >2.3 approximately < or =3.9, C: 3.9 approximately < or =5.4, D: >5.4 ng/dl), and
      the AUC, cut-off points, sensitivity, and specificity of the FT(3)/FT(4) ratios
      were calculated. The AUC and sensitivity of each group increased with the FT4
      levels (AUC: 57.8%, 72.1%, 91.1%, and 93.4%, respectively; sensitivity: 62.6%,
      50.0%, 77.8%, and 97.0%, respectively). The means +/- SE of the FT3/FT4 ratio in
      the Graves' disease groups were 3.1 +/- 0.22, 3.1 +/- 0.09, 3.2 +/- 0.06, and 3.1
      +/- 0.07, respectively, versus 2.9 +/- 0.1, 2.6 +/- 0.07, 2.5 +/- 0.12, and 2.3
      +/- 0.15, respectively, in the painless thyroiditis groups. In the painless
      thyroiditis patients, the difference in the FT3/FT4 ratio between group A and
      group D was significant (p<0.05). Thus, the FT3/FT4 ratio in patients with
      Graves' disease likely remains unchanged as the FT4 level rises, whereas this
      ratio decreases as the FT4 level rises in patients with painless thyroiditis. In
      conclusion, the FT3/FT4 ratios of patients with painless thyroiditis overlapped
      with those of patients with Graves' disease. However, this ratio was useful for
      differentiating between these two disorders when the FT4 values were high.

PMID- 16284431
TI  - Primary pituitary lymphoma presenting as hypophysitis.
AB  - A 47-year-old man had suffered from prolonged fever for two months without
      clinical evidence of infection. Blood biochemistry and endocrine dysfunction
      indicated that he had pituitary insufficiency. Thorough whole body imaging
      studies merely identified a 22 x 14 mm mass lesion in the sella turcica. Tumor
      pathology and special cell marker study revealed the infiltration of atypical T
      lymphoid cells and concomitant presence of some B-lymphoid cells. The fever
      subsided gradually following subtotal tumor resection and steroid
      supplementation. However, the mass lesion had invaded the cavernous sinus and
      optic chiasma shortly after surgery. Six months after his initial visit,
      metastasis lesions in the liver, the left adrenal gland, and retroperitoneal
      lymph nodes were discovered. In contrast to cells in the pituitary, the
      pathological investigation of the liver mass confirmed it to be exclusively of T
      cell origin. Therefore, it is plausible that the pituitary dysfunction was
      related to an inflammatory process, namely hypophysitis, as well as the T-cell
      lymphoma. This case exemplifies the rarely noted condition of primary pituitary
      lymphoma with concomitant hypophysitis. Clinical diagnosis is indiscernible until
      the occurrence of systemic tumor metastasis.

PMID- 16284432
TI  - Anaplastic thyroid carcinoma associated with Graves' disease.
AB  - This report concerns a 79-year-old woman with coexisting anaplastic thyroid
      carcinoma (ATC) and Graves' disease (GD). The patient was referred to our clinic
      because of palpitation and a palpable mass on the left side of her neck. Thyroid
      function tests showed hyperthyroidism with elevated thyroid-stimulating
      antibodies. Ultrasonography of the thyroid demonstrated an adenomatous nodule
      like marcated nodule (27.6 x 26.5 x 36.4 mm) with cystic degeneration inside the
      left lobe. (123)I thyroid scintigraphic imaging showed a cold area corresponding
      to the nodule with continuous uptake in the remaining thyroid tissue despite
      suppressed TSH levels. These findings led to a diagnosis of GD. On the other
      hand, the thyroid nodule could not be definitely diagnosed even after fine needle
      aspiration biopsy (FNAB) which produced findings suggestive of both papillary
      thyroid carcinoma and ATC. Open biopsy of the nodule showed an ATC. Regional
      lymph node metastases as well as multiple lung metastases, which could not be
      found at the initial visit, had been already developed by that time. Our case is
      pathophysiologically interesting because it suggests that GD or thyroid
      stimulating antibodies (TSAb) may stimulate malignant transformation of
      differentiated carcinoma. It is also clinically important because it indicates
      that all thyroid nodules, particularly palpable cold nodules, associated with GD
      require careful management to detect malignancy because they are at higher risk
      of harboring malignancy.

PMID- 16284433
TI  - Subacute thyroiditis developed in identical twins two years apart.
AB  - A 34-year-old woman was referred to our hospital complaining of sore throat and
      arthralgia. She had low-grade fever, tachycardia, and goiter with tenderness.
      Laboratory data revealed thyrotoxicosis and tests for acute inflammatory markers
      were positive. Thyroidal radioactive iodine uptake was below normal.
      Ultrasonography of thyroid revealed mild thyroid enlargement and hypoechogenic
      areas consistent with tenderness. Subacute thyroiditis was diagnosed and
      prednisone was administered. Two years later, her identical twin sister, who
      lives separately, was referred to our hospital because of neck pain, low-grade
      fever, and palpitation. She exhibited the same clinical picture as her twin
      sister, and was also diagnosed as having subacute thyroiditis. Although the cause
      of subacute thyroiditis remains unclear, viral infection has been implicated in
      the onset of subacute thyroiditis in genetically predisposed individuals. We
      could not identify the viruses, but heterozygotes for HLA-B35, which has been
      reported to be linked with subacute thyroiditis, were found in the twins. This
      supports the suspicion that genetic factors, including this HLA haplotype, play a
      critical role in the onset of subacute thyroiditis.

PMID- 16284434
TI  - Efficacy of glimepiride in patients with poorly controlled insulin-treated type 2
      diabetes mellitus.
AB  - We retrospectively investigated the effects of adding glimepiride in patients
      with type 2 diabetes showing suboptimal control by insulin therapy. Of 63
      patients with poorly controlled insulin-treated type 2 diabetes (baseline HbA1c,
      8.4 +/- 0.6%), 32 were treated with insulin alone and 31 were given glimepiride
      in addition to insulin. HbA1c values, daily insulin dose, body weight, blood
      pressure, plasma lipid concentrations, and the number of hypoglycemic events were
      recorded at weeks 0, 12, 24, 36, 48, 60, and 72. HbA1c decreased by 1.1%, from
      8.5 +/- 0.6% to 7.4 +/- 0.8% (P<0.0001) in patients treated with insulin plus
      glimepiride at 12 weeks, and improved glycemic control continued throughout the
      study. Required insulin dose was reduced significantly in patients treated with
      insulin plus glimepiride (from 29.4 +/- 14.5 to 22.3 +/- 12.1 units/day, P =
      0.0187). Body weight increased significantly in patients treated with insulin
      plus glimepiride (from 57.0 +/- 8.7 to 59.5 +/- 9.2 kg, P = 0.0232). Adding
      glimepiride showed little effect on blood pressure, plasma total cholesterol,
      triglyceride, or HDL-cholesterol. Serum C peptide concentrations increased
      significantly in patients treated with insulin plus glimepiride (from 1.01 +/-
      0.71 to 1.28 +/- 0.65 ng/ml, P = 0.0367). The number of hypoglycemic events did
      not differ between groups. Adding glimepiride to insulin therapy resulted in
      sustained improvement of glycemic control in patients with poorly controlled type
      2 diabetes.

PMID- 16284435
TI  - Hodgkin lymphoma in temporal association with growth hormone replacement.
AB  - The association between growth hormone (GH) replacement and malignancy has long
      been debated. We report a case of Hodgkin lymphoma that developed in temporal
      association with the initiation of GH replacement in a 57-year-old woman with
      panhypopituitarism secondary to a non-secretory pituitary macroadenoma. Treatment
      of her pituitary tumor included transphenoidal surgery, external beam radiation,
      Bromocriptine and Cabergaline therapy. In addition to replacement steroid,
      thyroid and sex hormones, she insisted on GH replacement. Approximately 2 years
      after GH initiation, the diagnosis of Hodgkin lymphoma was made. Although the
      exact contribution of GH to the development of Hodgkin disease in our patient is
      unclear and a causal effect cannot be concluded, the temporal association is
      suggestive, and warrants reporting as part of ongoing surveillance for potential
      complications of GH replacement.

PMID- 16284436
TI  - Mutations in the thyrotropin receptor signal transduction pathway in the
      hyperfunctioning thyroid nodules from multinodular goiters: a study in the
      Turkish population.
AB  - Many studies have been carried out to determine G(s) alpha and TSHR mutations in
      autonomously functioning thyroid nodules. Variable prevalences for somatic
      constitutively activating TSHR mutations in hot nodules have been reported.
      Moreover, the increased prevalence of toxic multinodular goiters in iodine
      deficient regions is well known. In Turkey, a country with high incidence rates
      of goiter due to iodine deficiency, the frequency of mutations in the thyrotropin
      receptor signal transduction pathway has not been evaluated up to now. In the
      present study, a part of the genes of the TSHR, G(s)alpha and the catalytic
      subunit of the PKA were checked for activating mutations. Thirty-five patients
      who underwent thyroidectomy for multinodular goiters were examined. Genomic DNAs
      were extracted from 58 hyperactive nodular specimens and surrounding normal
      thyroid tissues. Mutation screening was done by single-strand conformational
      polymorphism (SSCP) analysis. In those cases where a mutation was detected, the
      localization of the mutation was determined by automatic DNA sequencing. No
      G(s)alpha or PKA mutations were detected, whereas ten mutations (17%) were
      identified in the TSHR gene. All mutations were somatic and heterozygotic. In
      conclusion, the frequency of mutations in the cAMP signal transduction pathway
      was found to be lower than expected in the Turkish population most likely because
      of the use of SSCP as a screening method and sequencing only a part of TSHR exon
      10.

PMID- 16284437
TI  - Maternal thyroid function during pregnancy and puerperal period.
AB  - It has been noted that hypothyroidism in pregnant women can adversely affect the
      children's subsequent psychoneurotic development. Also, transient elevation of
      serum free thyroxine is occasionally seen in the first trimester of normal
      pregnancy. However, normal thyroid function during pregnancy and the puerperal
      period has not been clearly defined in Japan. The aim of this study was to assess
      maternal thyroid function during pregnancy and puerperal period in Japan. The
      concentrations of thyroid stimulating hormone (TSH), free triiodo-thyronine (free
      T(3)), free thyroxine (free T(4)) and thyroid binding capacity (TBC) of 522
      normal pregnant and puerperal women (119 in the first trimester; 132 in the
      second trimester; 135 in the third trimester and 136 in the early puerperium)
      were measured by electrochemiluminescence immunoassay. We compared the measured
      data with those of healthy nonpregnant control. Twenty-six (21.8%) of 119 women
      in the first trimester had lower TSH levels and 23 (16.9%) of 136 women in the
      early puerperium had higher TSH levels than the normal range of healthy
      nonpregnant controls. Free T(3) gradually decreased during pregnancy, although it
      remained within the normal control range. Eight (6.7%) of 119 women in the first
      trimester had high free T(4) levels, which gradually decreased during pregnancy.
      Sixty (44.4%) of 135 women in the third trimester had low free T(4) levels. The
      values of TBC in the second trimester increased compared with the first trimester
      and did not change in the third trimester and decreased after delivery. There
      were no correlations between maternal TSH and levels of thyroid hormones (free
      T(3) or free T(4)), except for TSH and free T(4) in the first trimester. In
      conclusion, we showed that maternal thyroid function, especially TSH and free
      T(4), changed during the course of pregnancy. In assessing the thyroid function
      associated with pregnancy, one needs to keep in mind the tendency toward low free
      T(4) levels in the third trimester and high TSH levels in the early puerperal
      period.

PMID- 16284438
TI  - Molecular scanning for mutations in the insulin receptor substrate-1 (IRS-1) gene
      in Turkish with type 2 diabetes mellitus.
AB  - Insulin receptor substrate-1 (IRS-1) is an endogenous substrate for the insulin
      receptor tyrosine kinase, which plays a key role in insulin signaling. Recent
      studies have identified several polymorphisms in the human IRS-1 gene (Irs-1)
      that are increased in prevalence among type 2 diabetic patients. To determine
      whether variation in the Irs-1 contributes to genetic susceptibility to type 2
      diabetes in Turkish people, PCR-RFLP and DNA sequencing method were utilized to
      analyze the coding region of Irs-1 in 70 subject and 116 control patients. Three
      missense mutations were detected (Gly972Arg, Ala512Pro, Ser892Gly). There was no
      significant association found with any of these variants and diabetes. The
      Gly972Arg mutation, however, was relatively more common in with 10/70 diabetic
      patients and 15/116 non-diabetic controls being heterozygous and 1/70 being and
      0/116 non-diabetic controls being homozygous for this variant. As a conclusion,
      Ala512Pro, Ser892Gly mutations were rare and Met613Val, Ser1043Tyr and Cys1095Tyr
      mutations were not found in the populations studied. Gly972Arg is more common
      than other known mutations in our population but may not be a major determinant
      in genetic susceptibility to type 2 diabetes.

PMID- 16284439
TI  - Further studies on episodic occurrence of congenital dysgenetic hypothyroidism in
      Osaka, Japan.
AB  - A total of 1,228,551 newborn babies, who were almost all of babies born in Osaka
      for 14 years (168 months), were screened for congenital primary hypothyroidism by
      an identical mass-screening program using the thyrotropin method, and 429
      patients with hypothyroidism due to thyroid dysgenesis (dysgenetic
      hypothyroidism) were found. The occurrence of the patients in every month was not
      random but episodic and the incidence was higher in the late autumn (from October
      to December). These observations support a hypothesis that some environmental
      factors may cause this disorder overtime and the possibility of relation with
      intrauterine viral infection was discussed.

PMID- 16284440
TI  - Systemic distribution of somatostatin receptor subtypes in human: an
      immunohistochemical study.
AB  - Somatostatin is well known to inhibit the hormone secretion of various peptides.
      This action has been considered to be generally mediated via six different
      specific somatostatin receptors (sstr), sstr1, sstr2A, sstr2B, sstr3, sstr4, and
      sstr5. It then becomes very important to demonstrate the localization of these
      sstr subtypes in order to elucidate the possible biological and/or clinical
      significance of somatostatin actions. These sstr subtypes have been demonstrated
      to be expressed throughout the human body, including the central nervous system,
      gastrointestinal tract, pancreas, kidney, and other organs, but its details,
      especially its systemic distribution and localization in tissue compartments,
      have yet to be examined thoroughly in human. Therefore, in this study, we
      examined the systemic localization of all six somatostatin receptors in normal
      human organs using immunohistochemistry with recently developed specific
      antibodies against these receptor subtypes. In all of the human tissues examined,
      various sstr subtypes were detected not only in parenchymal cells but also in
      various stromal cells such as lymphocytes, fibroblasts, and endothelial cells.
      Among human tissues in which the presence of sstr has not been previously
      reported, the parotid gland demonstrated immunoreactivity for sstr2B and sstr5,
      bronchial gland for sstr1, 2B, 3, 4, 5, parathyroid gland for sstr1, 3, 4, and
      duodenum for all subtypes immunoreactivity. The great majority of other organs
      examined demonstrated results consistent with those of previously reported
      biochemical studies. In pancreatic islet cells, only sstr2A was positive in all
      the cases but other sstr subtypes were associated with marked intraislet
      heterogeneity in their distribution. In stomach, all subtypes of receptor were
      detected in various cell types of the mucosa, but none in ECL cells of fundic
      gland. These findings demonstrated the broad systemic actions of somatostatin in
      non-endocrine cells.

PMID- 16284441
TI  - Vitamin D3 treatment for locally advanced thyroid cancer: a case report.
AB  - There are many intricacies in the surgical treatment of locally advanced thyroid
      cancer, including the medical management of the remaining functional organ and
      any cosmetic impairments, which are sometimes very difficult to manage and
      eventually carry a relatively high morbidity and mortality. Here, we report on a
      case of a 65-year-old female with an extremely locally-advanced thyroid cancer
      involving both lobes of the thyroid, blood vessels, trachea and esophagus.
      Despite the severity of her condition, oral administration of vitamin D3
      (alphacalcido) has stalled both the tumor growth and further increases of serum
      thyroglobulin (Tg) level, and has led to a good preservation of quality of life
      for the last two years. Several reports have previously demonstrated the efficacy
      of vitamin D3 to inhibit the proliferation of thyroid cancer cell lines in vitro,
      but clinical evidence has been limited so far. Therefore, this case report
      provides important evidence for the effectiveness of vitamin D3 therapy against
      advanced thyroid cancers.

PMID- 16284442
TI  - Familial occurrence of silent thyroiditis.
AB  - Two brothers and their mother, who had allergic rhinitis caused by Japanese cedar
      pollen, developed silent thyroiditis in spring. In addition, these three patients
      had the same HLA haplotype. Another brother, the father, and the paternal
      grandmother, who did not have allergic rhinitis caused by Japanese cedar pollen,
      did not show symptoms of silent thyroiditis. The present study indicates that
      genetic and/or environmental factors are important in the development of this
      familial type of silent thyroiditis.

PMID- 16284443
TI  - Insulin-induced lipohypertrophy: report of a case with histopathology.
AB  - An 82-year-old woman with type 2 diabetes had been treated with recombinant human
      insulin for 16 years. She developed large swellings in both sides of her lower
      abdomen. The masses were soft, painless, and located around her insulin injection
      sites. Based on the history and clinical features, a diagnosis of insulin-induced
      lipohypertrophy was made. Total resection revealed that the lesions were composed
      entirely of fatty tissue. Microscopic examination showed nests of mature
      adipocytes expanding toward the dermal reticular layer. The hypertrophic
      adipocytes were twice as large as those from normal subcutaneous areas and
      contained numerous small lipid droplets. Electron microscopic analysis also
      revealed a minor population of small adipocytes, suggesting active
      differentiation or proliferation. Thus, the possible in vivo effects of insulin
      on adipocytes were clearly observed in this case of insulin-induced
      lipohypertrophy. To our knowledge, this is the first report of insulin-induced
      lipohypertrophy with detailed histological examinations.

PMID- 16284444
TI  - Successful long-term treatment with once-daily injection of low-dose octreotide
      in an aged patient with insulinoma.
AB  - The patient was an 83-year-old woman who was admitted to our hospital for
      evaluation and treatment of chronic hypoglycemia that was first identified 3
      years earlier. Serum insulin and C-peptide levels were both elevated during
      hypoglycemia. Contrast abdominal computed tomography revealed a tumor in the body
      of the pancreas with blushing during the early phase, and insulinoma was
      diagnosed. The patient declined surgery because of advanced age, so treatment was
      started with octreotide, a somatostatin analogue. Hypoglycemia has been
      successfully controlled with low-dose, once-daily octreotide over 33 months. Few
      reports have described long-term octreotide administration for benign insulinoma.
      Moreover, this case is interesting from the perspective of hypoglycemic control
      using only low-dose, once-daily octreotide. Although somatostatin may induce
      hypoglycemia in insulinoma, treatment may be useful in patients who are not
      candidates for surgery, provided that careful monitoring is maintained.

PMID- 16284445
TI  - Enhanced expression of CD69 and CD25 antigen on human peripheral blood
      mononuclear cells by prolactin.
AB  - Several clinical reports have suggested that prolactin (PRL) plays an important
      role in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA)
      or systemic lupus erythematosus (SLE). We have investigated the influence of PRL
      on immune system, by evaluating the effects of PRL on the expression of CD69 and
      CD25 on human peripheral blood mononuclear cells (PBMCs). Human PBMCs obtained
      from healthy female volunteers were incubated with phytohemagglutinin (PHA) in
      the presence or absence of various concentrations of PRL. The expression of CD69
      and CD25 was monitored using immunofluorescence staining and flow cytometry. PRL
      significantly enhanced the expression of CD69 and CD25 on activated PBMCs
      compared with that in the absence of PRL (p<0.05, paired t-test). Increasing
      doses of PRL enhanced the expression of CD69 up to 2 microg/ml and CD25 up to 1
      microg/ml. The enhanced expression of CD69 was observed on CD8+ T lymphocytes but
      not on CD4+ T lymphocytes. Our data suggest that PRL can significantly enhance
      the expression of CD69 and CD25 molecule on human PBMCs when induced by PHA.
      However, PRL would have to be at optimal concentration in order to enhance their
      expression.

PMID- 16284446
TI  - Two novel mutations in the thyroid peroxidase gene with goitrous hypothyroidism.
AB  - We encountered a Japanese patient with goitrous hypothyroidism due to iodide
      organification defect in the thyroid gland. Sequence analysis identified two
      novel mutations (E378K in exon 8 and a heterozygous 10 base deletion of the
      intron 15-exon 16 boundary) in the thyroid peroxidase (TPO) gene. As individuals
      with goitrous hypothyroidism caused by TPO gene mutation develop thyroid cancer,
      regular and careful follow-up for such patients must be done.

PMID- 16284447
TI  - An infant case of Graves' disease with ophthalmopathy.
AB  - Graves' disease is a rare disorder in children, particularly in infants. Ocular
      manifestations of Graves' disease in children are even more rare and are mild
      compared to adults. We report a 3-year-old girl with Graves' ophthalmopathy who
      visited our clinic because of lacrimation. Her family had also noticed
      exophthalmos, goiter, irritability and increased appetite for more than 3 months.
      The ophthalmologist noted bilateral proptosis, eyelid erythema, lacrimation,
      entropion of the lower eyelid, and superficial keratitis. Her serum
      concentrations of free thyroxine and free triiodothyronine were high, and thyroid
      stimulating hormone (TSH) was low. Serum samples were markedly positive for
      antibodies to TSH receptor (TRAb) and thyroid-stimulating antibody (TSAb).
      Although hyperthyroidism was controlled with propylthiouracil within 3 weeks, her
      eye signs did not improve. We administered methylprednisolone pulse therapy for
      ophthalmopathy, but the effect was limited and the lacrimation due to entropion
      and superficial keratitis persisted. Titers of both TRAb and TSAb decreased
      slightly and transiently with the pulse therapy. One year later, both titers
      remained high and eye signs did not improve any more though she was clinically
      euthyroid. This might indicate that both TRAb and TSAb levels correlate with the
      clinical course. Therefore, TRAb or TSAb might be good indicators of progress of
      Graves' ophthalmopathy. Ocular manifestations of Graves' disease should be
      followed closely with measurements of both TRAb and TSAb even in infant cases.

PMID- 16284448
TI  - Thyrotoxic periodic paralysis.

PMID- 16284449
TI  - Neural encoding of olfactory recognition memory.
AB  - Our work with both sheep and mouse models has revealed many of the neural
      substrates and signalling pathways involved in olfactory recognition memory in
      the main olfactory system. A distributed neural system is required for initial
      memory formation and its short-term retention-the olfactory bulb, piriform and
      entorhinal cortices and hippocampus. Following memory consolidation, after 8 h or
      so, only the olfactory bulb and piriform cortex appear to be important for
      effective recall. Similarly, whereas the glutamate-NMDA/AMPA receptor-nitric
      oxide (NO)-cyclic GMP signalling pathway is important for memory formation it is
      not involved in recall post-consolidation. Here, within the olfactory bulb, up
      regulation of class 1 metabotropic glutamate receptors appears to maintain the
      enhanced sensitivity at the mitral to granule cell synapses required for
      effective memory recall. Recently we have investigated whether fluctuating sex
      hormone levels during the oestrous cycle modulate olfactory recognition memory
      and the different neural substrates and signalling pathways involved. These
      studies have used two robust models of social olfactory memory in the mouse which
      either involve social or non social odours (habituation-dishabituation and social
      transmission of food preference tasks). In both cases significant improvement of
      learning retention occurs when original learning takes place during the proestrus
      phase of the ovarian cycle. This is probably the result of oestrogen changes at
      this time since transgenic mice lacking functional expression of oestrogen
      receptors (ERalpha and ERbeta, the two main oestrogen receptor sub-types) have
      shown problems in social recognition. Therefore, oestrogen appears to act at the
      level of the olfactory bulb by modulating both noradrenaline and the glutamate/NO
      signalling pathway.

PMID- 16284450
TI  - Effects of exposure in utero to bisphenol a on the expression of aryl hydrocarbon
      receptor, related factors, and xenobiotic metabolizing enzymes in murine embryos.
AB  - To evaluate the effects of bisphenol A (BPA), a candidate endocrine disruptor
      (ED), on embryonic development, we examined the mRNA expression levels of the
      aryl hydrocarbon receptor (AhR; which binds with many EDs and plays crucial roles
      in their metabolism) and related factors [aryl hydrocarbon receptor repressor
      (AhRR) and AhR nuclear translocator (Arnt)], xenobiotic metabolizing enzymes
      [XMEs; cytochrome P450 1A1 (CYP1A1) and UDP-glucuronosyltransferase, and the
      glutathione S-transferase Ya subunit (GST)], in murine embryos exposed in utero
      to BPA (0.02, 2, 200, and 20,000 microg/kg/day) and 17beta-estradiol (E2; 5
      microg/kg/day, used as a positive control) at 6.5-13.5 or 6.5-17.5 days post
      coitum (dpc) using the quantitative real-time reverse transcription-polymerase
      chain reaction (RT-PCR) method. Protein levels of CYP1A1 and GST in embryonic
      livers were estimated by Western immunoblotting. Exposure in utero to BPA [0.02
      (1/100 dose of environmental exposure), 2, 200, and 20,000 microg/kg/day]
      increased AhR mRNA expression in the cerebra, cerebella, and gonads (testes and
      ovaries) of male and female mid-and late-developmental stage (14.5- and 18.5-dpc,
      respectively) embryos. BPA dose-independently up-regulated the expression of AhRR
      and Arnt in mid- and late-stage embryos. BPA had no remarkable effect on the mRNA
      levels of XMEs in mid-stage embryos, but dose-dependently up-regulated the
      expression in late-stage embryos. Moreover, the protein levels of these enzymes
      in the livers of late-stage embryos were increased. The present findings revealed
      that exposure to BPA in utero disrupts the expression of AhR and related factors
      and of xenobiotic metabolizing enzymes, and that mid-stage embryos, in the
      organogenic stage, are sensitive to BPA.

PMID- 16284451
TI  - Changes in the localization of antigen presenting cells and T cells in the utero
      vaginal junction after repeated artificial insemination in laying hens.
AB  - The goal of our present study was to observe whether the populations of antigen
      presenting cells (Ia+ cells) and T cell subsets (CD4+ and CD8+ T cells) change in
      the utero-vaginal junction (UVJ) of Rhode Island Red laying hens that showed
      dramatic declines in fertility after repeated artificial insemination (AI). Rhode
      Island Red laying hens were divided into two groups: a virgin group (R-V) and
      artificial inseminated group (R-AI), which was exposed to weekly AI for a period
      of 3 mo. Undiluted fresh semen collected from healthy Tosa-Jidori roosters, a
      native Japanese breed maintained in Kochi Prefecture, was used for AI. The UVJ
      tissues were processed for frozen sections, and Ia+ cells and CD4+ and CD8+ T
      cells were identified by immunohistochemistry. The Ia+ cells and CD4+ and CD8+ T
      cells were observed in the stroma and mucosal epithelium of UVJ in both the R-AI
      and R-V birds. The frequencies of them in the stroma were significantly higher in
      R-AI than R-V. The higher frequency of Ia+ cells in the UVJ of R-AI group
      indicated a greater potential capability for antigen presentation to CD4+ cells.
      The significant increase in CD8+ and CD4+ T cells in the UVJ of R-AI birds might
      be the result of a homing process of lymphocytes, which may affect sperm
      survivability and fertility.

PMID- 16284454
TI  - Clinical management of depression and anxiety in HIV-infected adults.

PMID- 16284455
TI  - Presence of JC virus-specific CTL in the cerebrospinal fluid of PML patients:
      rationale for immune-based therapeutic strategies.
AB  - OBJECTIVES: There is urgent need of a treatment for progressive multifocal
      leukoencephalopathy (PML), caused by the polyomavirus JC (JCV). To evaluate the
      rationale for immunotherapy of PML, we explored whether JCV-specific cytotoxic T
      lymphocytes (CTL) can penetrate the central nervous system (CNS). In addition, we
      studied the breadth of their T-cell receptor (TCR) repertoire, and sought to
      establish a reliable method to expand these cells in vitro. DESIGN AND METHODS:
      We enrolled 18 patients in this study, including 16 with proven or possible PML
      (15 HIV-positive and one HIV-negative), and two HIV-positive patients with other
      neurological diseases. Detection of JCV-specific CTL in the blood and the
      cerebrospinal fluid was performed by Cr release and tetramer staining assays in
      15 patients. RESULTS: Of 11 PML patients with analyzable cerebrospinal fluid
      (CSF), two had no detectable JCV-specific CTL in the blood and CSF and died 3.7
      and 7.2 months later. The nine remaining patients had an inactive course of PML
      and detectable JCV-specific CTL in the blood. In addition, four of them (44%)
      also had detectable JCV-specific CTL in the CSF. Both HIV-positive patients with
      OND had detectable JCV-specific CTL in the blood and one in the CSF. Using
      tetramer technology, we obtained highly enriched JCV-specific CTL lines that were
      able to kill target cells presenting JCV peptides. The breadth of the TCR
      repertoire was CTL epitope dependent. CONCLUSIONS: These results indicate that
      JCV-specific CTL are present in the CNS of PML patients and pave the way for an
      immune-based therapeutic approach.

PMID- 16284456
TI  - Loss of IL-7Ralpha is associated with CD4 T-cell depletion, high interleukin-7
      levels and CD28 down-regulation in HIV infected patients.
AB  - OBJECTIVE: Elevated levels of interleukin (IL)-7 are present in the blood of HIV
      positive patients and it is known that IL-7 receptor (IL-7R)alpha expression
      decreases on T cells during HIV infection. The subset(s) of T cells with low IL
      7Ralpha and the consequence of low IL-7Ralpha expression for T-cell survival are
      poorly characterized. DESIGN: The frequency of IL-7Ralpha-negative T cells in HIV
      positive patients was studied in relation to CD4 T-cell counts, IL-7
      concentration and survival in culture. We analysed IL-7Ralpha expression in
      different T-cell populations and in relation to Bcl-2 expression. METHODS:
      Specimens from 38 HIV-1 patients and 17 controls were examined. IL-7Ralpha and
      Bcl-2 expression in different T-cell populations was studied by flow cytometry.
      The influence of IL-7Ralpha expression on T-cell survival was studied by
      culturing T cells in the presence of IL-7. RESULTS: Down-regulation of IL-7Ralpha
      on T cells correlated with depletion of CD4 T cells (P < 0.001) and also with
      increased concentration of serum IL-7 (P < 0.05). The decreased IL-7Ralpha
      expression was associated with low Bcl-2 expression and with the reduced survival
      capacity of T cells in the presence of IL-7 in vitro. Particularly, T cells with
      memory phenotype showed a decreased IL-7Ralpha expression in association with
      CD28 down-regulation. CONCLUSIONS: The positive effects of IL-7 on survival and
      homeostatic proliferation of T cells might be severely impaired in HIV-infected
      individuals due to IL-7Ralpha down-regulation. Differentiation towards a CD28
      negative memory phenotype in response to chronic activation may lead to an
      overall decrease of IL-7 mediated survival within the peripheral T-cell pool.

PMID- 16284457
TI  - Indirubin-3'-monoxime, a derivative of a Chinese antileukemia medicine, inhibits
      P-TEFb function and HIV-1 replication.
AB  - OBJECTIVE: To evaluate the effects of the cyclin dependent kinase (CDK) inhibitor
      Indirubin-3'-monoxime (IM) on Tat-mediated transactivation function, a step of
      the HIV-1 cycle that is not currently targeted in antiviral therapy. METHODS: The
      effects of IM on CDK implicated in HIV-1 Tat transactivation function were
      evaluated by kinase assays, transfection experiments, RNase protection assay and
      RT-PCR analysis of viral transcripts. The antiviral effect of IM was investigated
      in cells from HIV-1 infected individuals as well as in cell lines, primary
      lymphocytes and monocyte-derived macrophages. The antiviral activity of IM was
      also tested against drug-resistant HIV-1. RESULTS: IM inhibits the kinase
      activity of CDK9 [50% inhibitory concentration (IC50) of 0.05 microM], the
      catalytic subunit of Positive transcription elongation factor b (P-TEFb).
      Inhibition of CDK9 activity by IM results in abrogation of Tat-induced expression
      of HIV-1 RNA in cell lines. In addition, IM inhibits the replication of HIV-1 in
      both peripheral blood mononuclear cells (IC50 of 1 microM) and macrophages (IC50
      of 0.5 microM). IM is effective against primary and drug-resistant strains of HIV
      1. Importantly, the antiviral effects of the drug were seen at concentrations
      that did not affect cell proliferation. CONCLUSIONS: Non-toxic concentrations of
      IM inhibit HIV-1 by blocking viral gene expression mediated by the cellular
      factor P-TEFb. The drug is effective against wild-type and drug-resistant strains
      of HIV-1. IM may help control replication of HIV-1 in patients by disrupting a
      step of the HIV-1 cycle that is not being targeted in current antiretroviral
      treatments.

PMID- 16284458
TI  - Modulation of the intracellular accumulation of saquinavir in peripheral blood
      mononuclear cells by inhibitors of MRP1, MRP2, P-gp and BCRP.
AB  - BACKGROUND: The efflux transporters P-glycoprotein (P-gp), multidrug resistance
      associated proteins (MRP) and breast cancer resistance protein (BCRP) limit the
      accumulation of antiretrovirals in cell lines but it is more important to know
      whether the expression of these transporters in peripheral blood mononuclear
      cells (PBMC) impacts cellular drug concentrations. OBJECTIVES: To study the
      transport and accumulation of saquinavir (SQV) in PBMC and the effects of
      specific inhibitors of MRP1, MRP2, P-gp and BCRP. METHODS: Transport and
      accumulation of [H]-SQV was measured in PBMC in the absence or presence of
      specific and non-specific inhibitors of MRP1, MRP2, P-gp and BCRP. Flow
      cytometric, western blot and real-time PCR assays were used to examine the
      relative expression of the drug efflux transporters in the same batches of PBMC.
      RESULTS: MRP2 is present in PBMC. The expression of P-gp, MRP1, MRP2 (mRNA) and
      BCRP all displayed batch-to-batch variability. Specific and non-specific
      inhibitors of MRP1, P-gp and MRP2 significantly increased the baseline
      accumulation of SQV. Accumulation of SQV was not correlated with the expression
      of any single transporter. CONCLUSIONS: Multiple drug efflux transporters are
      important in the intracellular accumulation of SQV in PBMC. If drug efflux
      contributes towards virological failure, then all contributing transporters will
      need to be inhibited.

PMID- 16284459
TI  - Withdrawal of Pneumocystis jirovecii prophylaxis in HIV-infected children under
      highly active antiretroviral therapy.
AB  - OBJECTIVE: In HIV-infected adults Pneumocystis jirovecii pneumonia (PCP)
      prophylaxis can be safely withdrawn after immune reconstitution due to the
      introduction of highly active antiretroviral therapy (HAART). With regard to
      children only a small amount of data has been published. The present study
      investigated whether the withdrawal of PCP prophylaxis after immune
      reconstitution is safe in HIV-infected children. METHODS: A retrospective
      analysis at 10 European centers belonging to the Pediatric European Network on
      the treatment of AIDS (PENTA) using a standardized questionnaire. RESULTS: A
      total of 113 questionnaires were received. In 82 children the indication for PCP
      prophylaxis was provided following Centers for Disease Control (CDC) guidelines
      (72 primary and 10 secondary). Prophylaxis was withdrawn after the CD4 cell count
      increased above the age-related CDC thresholds. The observation period off
      prophylaxis was 335 years (300 years for primary and 35 years for secondary
      prophylaxis) and the median time per patient off prophylaxis was 4.1 years
      (range, 0.3-7.7 years). No episode of PCP occurred during the study period. In
      comparison with the incidence rate from historical data before the introduction
      of PCP prophylaxis and HAART, this was a significant reduction (P < 0.05).
      CONCLUSIONS: The increase in CD4 cell count provides functional reconstitution of
      the immune system in children. Our data suggests that the risk of developing a
      PCP after immune reconstitution is sufficiently low to withdraw PCP prophylaxis.

PMID- 16284460
TI  - Tuberculosis among HIV-infected patients receiving HAART: long term incidence and
      risk factors in a South African cohort.
AB  - OBJECTIVES: To determine the long-term incidence of tuberculosis (TB) and
      associated risk factors among individuals receiving HAART in South Africa.
      DESIGN: Prospective cohort study. METHODS: Microbiologically or histologically
      confirmed incident TB was identified in a hospital-based cohort of 346 patients
      receiving HAART between 1996 and 2005 in Cape Town. RESULTS: The TB incidence
      density rate was 3.5/100 person-years in the first year and significantly
      decreased during follow-up, reaching 1.01/100 person-years in the fifth year (P =
      0.002 for trend). TB incidence during the study was highest among patients with
      baseline CD4 cell counts < 100 cells/microl and those with World Health
      Organization (WHO) clinical stage 3 or 4 disease (5.71 and 3.88/100 person-years,
      respectively). Risk of TB was independently associated with CD4 cell count < 100
      cells/microl (adjusted risk ratio [ARR], 2.38; 95% confidence interval (CI), 1.01
      5.60; P = 0.04), WHO stage 3 or 4 disease (ARR, 3.60; 95% CI, 1.32-9.80; P =
      0.01) and age < 33 years (ARR, 2.86; 95% CI, 1.29-6.34; P = 0.01). Risk of TB was
      not independently associated with plasma viral load, previous history of TB, low
      socioeconomic status or sex. Despite similar virological responses to HAART,
      blood CD4 cell count increases were much smaller among patients who developed TB
      than among those who remained free of TB. CONCLUSIONS: Incidence of TB continues
      to decrease during the first 5 years of HAART and so HAART may contribute more to
      TB control in low-income countries than was previously estimated from short-term
      follow-up. Patients with advanced pretreatment immunodeficiency had persistently
      increased risk of TB during HAART; this may reflect limited capacity for immune
      restoration among such patients.

PMID- 16284461
TI  - Is there evidence for an increase in the death rate from liver-related disease in
      patients with HIV?
AB  - BACKGROUND: Increases in deaths due to liver-related disease (LRD) among HIV
      infected individuals have been reported although the influence of combination
      antiretroviral therapy (cART) on LRD is controversial. AIMS: To determine changes
      over time in the death rate from LRD and if longer exposure to cART was
      associated with an increased death rate from LRD in 10 937 patients from
      EuroSIDA, an observational longitudinal cohort study. RESULTS: A total of 184
      (1.7%) died from LRD during 52 236 person-years of follow-up (PYFU). The death
      rate from LRD declined from 6.9 per 1000 PYFU before 1995 [95% confidence
      interval (CI), 3.9-9.9] to 2.6 at/after 2004 (95% CI, 1.6-4.0). When the current
      CD4 cell count and other factors were taken into account, there was a 13%
      increase in the death rate from LRD per year (95% CI, 5-20%, P = 0.0008). In
      patients who had started cART, there was a 12% increase in the death rate from
      LRD per additional year exposure to cART (95% CI, 4-20%, P = 0.022) after
      adjustment for current CD4 cell count and other factors. CONCLUSIONS: Death rates
      from LRD appeared to decrease across Europe. However after adjustment for the
      current CD4 cell count, and therefore increases in CD4 cell counts in patients
      taking cART, there was a significant increase over time in death rates from LRD.
      In patients with similar CD4 cell counts, longer exposure to cART was associated
      with an increased death rate from LRD. This may be due to direct liver toxicity
      of antiretrovirals, progression of liver disease due to hepatitis B virus or
      hepatitis C virus over time as patients survive longer, or some other factor.

PMID- 16284462
TI  - Absence of association between MDR1 genetic polymorphisms, indinavir
      pharmacokinetics and response to highly active antiretroviral therapy.
AB  - OBJECTIVE: The relationship between MDR1 single nucleotide polymorphisms (SNP)
      and the pharmacokinetic or pharmacodynamic responses to protease inhibitors has
      been recently challenged. AIM: The objective of the present study was to
      determine whether MDR1 genetic polymorphisms in exons 21 and 26 (G2677T/A and
      C3435T) are in association with indinavir (IDV) plasma concentrations and/or
      therapeutic response to highly active antiretroviral therapy (HAART) in HIV
      infected patients treated with unboosted IDV containing regimens. METHODS: MDR1
      genotyping was performed in a population of 139 HIV-1-positive patients followed
      during 72 weeks, as part of the previous study called ANRS 081 'Trianon'. The
      primary study was a randomized trial comparing over 72 weeks the efficacy of two
      antiretroviral drug combinations in a population of adult HIV-1-infected
      patients: group 1, [lamivudine (3TC) - stavudine (d4T) - IDV (800 mg three times
      daily)] and group 2, [Nevirapine (NVP) - d4T - IDV (1000 mg three times daily)].
      RESULTS: MDR1 SNPs analyzed separately or combined into haplotypes did not show
      any significant association with IDV pharmacokinetics nor response to HAART. Mean
      modelled IDV peak and trough concentrations, as well as clearance modelled from
      pharmacokinetic model, after 8 weeks of therapy were not significantly different
      between patients carrying the wild-type haplotype GG-CC (at position 2677 and
      3435 respectively) and others. CONCLUSIONS: Our results do not support an
      association between MDR1 genetic polymorphisms and modelled IDV clearance or
      clinical response to HAART.

PMID- 16284463
TI  - HIV infection and sexually transmitted infections among men who have sex with men
      in Senegal.
AB  - BACKGROUND: No epidemiological study has been conducted on HIV and vulnerability
      to sexually transmitted diseases (STI) among men who have sex with men (MSM) in
      sub-Saharan Africa. METHOD: A survey including questionnaire, physical
      examination and detection of HIV and STI was carried out among 463 MSM, aged 18
      52 years, recruited through the snowball technique in five urban sites throughout
      Senegal. RESULTS: A total of 21.5% of men were found to be infected with HIV [95%
      confidence interval (CI), 17.8-25.6]. Active syphilis, positive serology for
      herpes simplex virus (HSV)-2, and polymerase chain reaction detection in urine of
      Chlamydia and gonorrhea infections were recorded in 4.8, 22.3, 4.1 and 5.4% of
      participants, respectively. Most respondents reported sex with women (94.1%). In
      the month preceding the interview, 24% reported at least one unprotected
      insertive anal intercourse with a male partner, 20% at least one unprotected
      receptive anal intercourse, and 18% at least one unprotected intercourse with a
      female partner. Genital examination showed that 5% of participants had at least
      one clinical sign of STI. Factors associated with HIV infection were age group,
      the reporting of more than nine lifetime male partners [odds ratio (OR), 3.76;
      95% CI, 1.61-8.79], being a waiter or bartender (OR, 3.33; 95% CI, 1.41-7.84),
      and living in Dakar (OR, 3.33; 95% CI, 1.07-3.43). CONCLUSION: Men who have sex
      with men in Senegal are highly infected with HIV and other STI. Intervention
      programs targeting this population are urgently needed, given their particular
      vulnerability and because infections are likely to disseminate into the general
      population given the high proportion of bisexual activity in this community.

PMID- 16284464
TI  - Early mortality among adults accessing a community-based antiretroviral service
      in South Africa: implications for programme design.
AB  - OBJECTIVES: To determine rates, risk factors and causes of death among patients
      accessing a community-based antiretroviral treatment (ART) programme both prior
      to and following initiation of treatment. METHODS: All in-programme deaths were
      ascertained between September 2002 and March 2005 among treatment-naive patients
      enrolled into a prospective community-based ART cohort in Cape Town, South
      Africa. RESULTS: Of 712 patients (median CD4 cell count, 94 cells/microl), 578
      (81%) started triple ART a median of 29 days after enrollment. 68 (9.5%) patients
      died during 563 person-years of observation. The high pretreatment mortality rate
      of 35.6 deaths/100 person-years [95% confidence interval (CI), 23.0-55.1)
      decreased to 2.5/100 person-years (95% CI, 0.9-6.6) at 1 year among those who
      received ART. However, within the first 90 days from enrollment, 29 of 44 (66%)
      deaths occurred among patients awaiting ART; these would not be identified by an
      on-treatment analysis. Multivariate analysis showed that risk of death (both pre
      treatment and on-treatment) was independently associated with baseline CD4 cell
      count and World Health Organization (WHO) clinical stage; stage 4 disease was the
      strongest risk factor. Major attributed causes of death were wasting syndrome,
      tuberculosis, acute bacterial infections, malignancy and immune reconstitution
      disease. CONCLUSIONS: Most early in-programme deaths occurred among patients with
      advanced immunodeficiency but who had not yet started ART. Programme evaluation
      using on-treatment analyses greatly underestimated early mortality. This
      mortality would be reduced by minimizing unnecessary in-programme delays in
      treatment initiation and by starting ART before development of WHO stage 4
      disease.

PMID- 16284465
TI  - A randomized controlled safety and acceptability trial of dextrin sulphate
      vaginal microbicide gel in sexually active women in Uganda.
AB  - OBJECTIVE: To assess the safety of dextrin sulphate (DS) gel compared to placebo
      gel in terms of local and systemic adverse events, and to determine the
      acceptability of dextrin sulphate gel. DESIGN: A 4-week randomized trial of DS
      intra-vaginal gel, partially blinded, with placebo and observation control arms.
      Participants were randomized to use DS gel twice daily, placebo gel twice daily,
      DS gel pre-sex, or into an observation only arm. METHODS: Sexually active women
      were recruited from post natal and HIV clinics at Nsambya Hospital, Kampala,
      Uganda. Screening, enrollment and follow-up visits took place every 1 or 2 weeks
      over an 8-week period and consisted of questionnaire interviews, colposcopy
      examinations, sexually transmitted infection screen and routine laboratory
      testing. RESULTS: Out of a total of 172 women screened, 109 were randomized to
      use DS gel twice daily (65 women), placebo gel twice daily (15 women), DS gel pre
      sex (nine women) or into an observation only arm (20 women). Two individuals had
      abnormal colposcopy findings in the DS twice daily gel use arm. Vaginal bleeding
      was reported as frequently by participants in the active gel arm as by
      participants in the placebo and observation only arms. No clinically significant
      difference was observed between arms in terms of vaginal flora, Candida,
      haemoglobin, white cell count, platelets, thrombin time, activated partial
      thromboplastin time, creatinine and aspartate aminotransferase results after 4
      weeks of gel use. DS gel appeared to be acceptable to over 95% of the users.
      CONCLUSIONS: Results show a satisfactory safety and acceptability profile of
      dextrin sulphate gel.

PMID- 16284467
TI  - An international screening tool for HIV dementia.

PMID- 16284466
TI  - Expanded Phase I safety and acceptability study of 6% cellulose sulfate vaginal
      gel.
AB  - BACKGROUND: An expanded Phase I trial was performed to assess the safety and
      acceptability of 6% cellulose sulfate gel (CS) in comparison with K-Y Jelly.
      METHODS: Sexually abstinent (cohort I) and sexually active (cohort II) women in
      India, Nigeria and Uganda applied 3.5 ml of either 6% CS gel or K-Y Jelly for
      seven consecutive days. Safety was assessed by symptoms and signs (including
      colposcopy) of genital irritation, review of adverse events, and by changes in
      vaginal health as assessed by microscopy. RESULTS: One hundred and eighty women
      (90 on CS and 90 on K-Y Jelly) were enrolled. Baseline characteristics of women
      in both gel groups were similar. In cohort I, six (14%) women on CS and 12 (27%)
      on K-Y Jelly reported genital symptoms, two (in K-Y Jelly group) of whom withdrew
      from the study. New colposcopy findings or findings showing deterioration were
      detected in four (9%) women on CS and nine (21%) women on K-Y Jelly in cohort I.
      Two women on CS and three on K-Y Jelly in cohort II reported genital symptoms.
      Five women (11%) in each gel group in cohort II had new colposcopy findings or
      findings showing deterioration. The differences between the gel groups were not
      statistically significant. The majority of women had no problem with their
      assigned product. CONCLUSION: A vaginal application of 6% cellulose sulfate twice
      daily for seven consecutive days is as safe and well tolerated as a similar
      regimen of K-Y Jelly. Further development of 6% CS for prevention of HIV and
      pregnancy is recommended.

PMID- 16284468
TI  - Resistance after single-dose nevirapine prophylaxis emerges in a high proportion
      of Malawian newborns.
AB  - The administration of single-dose nevirapine to women in labor and their infants
      can prevent HIV-1 mother-to-child transmission. We examined nevirapine resistance
      in infants who were HIV-1 infected despite single-dose nevirapine prophylaxis,
      including 18 Ugandan infants (HIVNET 012 trial, nine subtype A and nine subtype
      D) and 23 Malawian infants (NVAZ trial, all subtype C). Nevirapine resistance was
      more frequent in infants with subtype C than with subtypes A and D (87 versus
      50%, P = 0.016).

PMID- 16284469
TI  - Amount of lymphatic tissue fibrosis in HIV infection predicts magnitude of HAART
      associated change in peripheral CD4 cell count.
AB  - The structure of lymphatic tissues is an important component of lymphatic tissue
      T-cell homeostasis. Collagen deposition in lymphatic tissues (common in HIV
      infection) disrupts the niche and limits the size of the resident CD4 cell
      population. In this report we show that a single measurement of lymphatic tissue
      collagen predicts the magnitude of recovery of the peripheral CD4 cell pool with
      HAART (P < 0.001). This suggests that collagen-targeted therapies might be of
      benefit.

PMID- 16284471
TI  - Determinants of HIV drug resistance mutations in plasma virus after treatment
      interruption.
AB  - This study examines the utility of resistance testing during treatment
      interruption, making comparisons with the current IAS guidelines. A total of
      188/1279 tests (14%) were performed during treatment interruption; 69/188 tests
      (36.7%) demonstrated key mutations. Time off therapy and the total number of
      previous drugs were both significantly associated with the presence of mutations.
      We conclude that resistance testing is of value up to 3 months after treatment
      interruption, and may convey some benefit up to 12 months.

PMID- 16284470
TI  - High-risk sexual behaviour among London gay men: no longer increasing.
AB  - Among gay men surveyed annually in central London gyms, the percentage reporting
      high-risk sexual behaviour with a casual partner increased from 6.7% in 1998 to
      15.2% in 2001 (P < 0.001). However, between 2002 and 2005 the percentage
      reporting high-risk sexual behaviour with a casual partner remained stable for
      HIV-negative and never-tested men (P > or = 0.3), with some evidence of a decline
      for HIV-positive men (adjusted odds ratio 0.69 per year, 95% confidence interval
      0.48, 0.99, P = 0.047).

PMID- 16284472
TI  - Efficacy of pegylated interferon alpha-2b for the treatment of chronic delta
      hepatitis in a patient co-infected with HIV.

PMID- 16284473
TI  - Limited positive predictive value of resistance testing in treatment-experienced
      patients.

PMID- 16284474
TI  - Chronic necrotizing pulmonary aspergillosis after tuberculosis in an HIV-positive
      woman: an unusual immune reconstitution phenomenon?

PMID- 16284475
TI  - Might male circumcision be more protective against HIV in the highly exposed? An
      immunological hypothesis.

PMID- 16284476
TI  - Alveolar bone necrosis and tooth exfoliation secondary to herpes zoster in the
      setting of HIV/AIDS.

PMID- 16284477
TI  - A new strategy for CD4 T-cell monitoring of HIV-positive patients at remote
      facilities in Cambodia.

PMID- 16284478
TI  - Address of the president of the Southern Society for Clinical Investigation: on
      the importance of mentoring.

PMID- 16284479
TI  - Presentation of the SSCI founders' medal for 2005 to Richard D. deShazo, MD.

PMID- 16284480
TI  - Southern society founders' medal acceptance.

PMID- 16284481
TI  - The proinflammatory heart failure phenotype: a case of integrative physiology.

PMID- 16284483
TI  - Southern Society for Clinical Investigation.

PMID- 16284482
TI  - A lethal tetrad in diabetes: hyperglycemia, dyslipidemia, oxidative stress, and
      endothelial dysfunction.
AB  - This paper addresses the consequences of diabetes and obesity, diseases that have
      become epidemic in our society, particularly in the past 20 years. Specifically,
      it summarizes current knowledge about some of the risk factors and mechanisms for
      the vascular complications of diabetes. These complications can be broadly
      divided into microvascular disease, such as diabetic retinopathy and diabetic
      nephropathy, and macrovascular disease, such as accelerated atherosclerosis, and
      they are the main cause for morbidity and premature mortality among diabetic
      patients. The roles of hyperglycemia, dyslipidemia and dyslipoproteinemia,
      oxidative stress, and endothelial dysfunction will be considered. Finally, the
      "treatment gap" will be addressed. This gap refers to our failure to achieve
      currently accepted goals to reduce established risk factors for complications in
      the clinical management of diabetic patients.

PMID- 16284484
TI  - Constitution and bylaws Southern Society for Clinical Investigation.

PMID- 16284485
TI  - Part 2: use of echocardiography in the evaluation of patients with suspected
      cardioembolic stroke.

PMID- 16284486
TI  - Panaortitis: diagnosis via fluorodeoxyglucose positron emission tomography.
AB  - A 57-year-old woman was admitted with a 2-month history of low-grade fever,
      malaise, and weight loss. Physical examination findings were unremarkable except
      for a systolic murmur of a known mild aortic regurgitation. Laboratory tests
      revealed only mild leukocytosis and an elevated sedimentation rate. Serology
      tests for viral and bacterial pathogens, blood and urine cultures, and immunology
      tests had negative results. Total body computed tomography, transesophageal
      echocardiography, and biopsies of bone, liver, and temporal arteries were normal.
      Wide-spectrum antibiotics effected no change in the patient's illness. Low-dose
      steroids given for a suspected polymyalgia rheumatica caused only minimal and
      transient improvement. Re-evaluation showed no new findings. Fluorodeoxyglucose
      positron emission tomography (FDG-PET) was done and showed an abnormally
      increased uptake along the aortic arch, the descending aorta, and bilaterally in
      the subclavian and carotid arteries, compatible with arteritis. High-dose
      steroids and later methotrexate were given and caused obvious improvement, with
      complete resolution of symptoms. We conclude that FDG-PET should be a part of the
      usual work-up of fever of unknown origin, especially in cases in which routine
      investigation reveals no cause.

PMID- 16284487
TI  - Hypoglycemia associated with the use of gatifloxacin.
AB  - We present the histories, clinical findings, and hospital course of three
      patients who developed hypoglycemia after receiving gatifloxacin. Possible
      mechanisms for the hypoglycemia are outlined. CASE 1: A 89-year-old diabetic male
      receiving glyburide was given a single dose of gatifloxacin for bronchitis.
      Thirteen hours later, he was found to be unresponsive with a blood glucose level
      of 34 mg/dL. The hypoglycemia resolved within 24 hours of stopping gatifloxacin.
      CASE 2: A 80-year-old nondiabetic woman with end-stage renal disease and recent
      surgery was treated with gatifloxacin, cefepime, and metronidazole for pneumonia.
      Sixteen hours later, her serum glucose level was 61 mg/dL, and over the next 24
      hours was as low as 39 mg/dL. The hypoglycemia resolved within 40 hours of
      stopping gatifloxacin. CASE 3: A 58-year-old diabetic man receiving glyburide was
      admitted for myocardial infarction and renal failure. Twelve hours after
      receiving gatifloxacin for pneumonia, his blood glucose level was 60 mg/dL and
      was as low as 42 mg/dL between 2 and 22.5 hours of a second dose of gatifloxacin.
      The hypoglycemia resolved within 24 hours of stopping gatifloxacin. CONCLUSIONS:
      Gatifloxacin use may precipitate hypoglycemia in diabetic patients receiving oral
      hypoglycemic agents and in nondiabetic patients with chronic renal failure.
      Discontinuation of gatifloxacin results in improvement in glucose homeostasis.

PMID- 16284488
TI  - Subacute pulmonary manifestation in a survivor of severe paraquat intoxication.
AB  - Paraquat has been widely used as a nonselective contact herbicide since 1962. It
      is highly toxic for humans, and many cases of acute poisoning, especially
      intentional self-poisoning, have been reported over the past few decades in
      developing countries. Ingestion of a threshold volume results in multiple organ
      failure and death after a longer period of time, but aggressive clinical studies
      are rarely done when the diagnosis is clear. We report the case of a patient who
      survived severe paraquat intoxication; he presented with subacute pulmonary
      manifestations including physiologic dysfunction and abnormalities on
      radiographs.

PMID- 16284489
TI  - Hepatic cirrhosis caused by low-dose oral amiodarone therapy.
AB  - A 63-year-old man presented with ascites after therapy with amiodarone, 200 mg
      orally once per day for 22.5 months. A liver biopsy showed grade 3 chronic
      hepatitis and micronodular cirrhosis. The presence of striking microvesicular
      steatosis on light microscopy and lysosomal inclusion bodies on electron
      microscopy suggested amiodarone hepatotoxicity. This is the first reported case
      of amiodarone-induced hepatic cirrhosis associated with chronic treatment with
      200 mg orally once per day for less than 2 years.

PMID- 16284492
TI  - IGF-I, IGFBP-3 and breast cancer in young women: a pooled re-analysis of three
      prospective studies.
AB  - Prospective cohort studies on breast cancer risk among premenopausal women and
      insulin-like growth factor I (IGF-I) concentrations have so far included only few
      cases, and have shown inconsistent relative risk estimates. We pooled 220 cases
      of breast cancer diagnosed before age 50, and 434 control subjects, from three
      prospective studies in New York (USA), Umea (Northern Sweden) and Milan (Italy),
      and we measured IGF-I and insulin-like growth factor binding protein 3 (IGFBP-3)
      with common enzyme-linked immunosorbent assays. Overall, IGF-I and IGFBP-3
      measurements obtained by the common method showed a positive but not significant
      relationship with breast cancer risk (odds ratios (ORs) 0.90 [95% confidence
      intervals (95% CI) 0.50-1.62], 1.63 [0.89-2.97], 1.46 [0.78-2.73] and 1.41 [0.75
      2.63] for quintiles of IGF-I, and ORs 0.98 [0.54-1.75], 1.06 [0.59-1.91], 1.04
      [0.58-1.87] and 1.77 [0.97-3.24] for quintiles of IGFBP-3). Our results give only
      moderate support for an association of blood IGF-I with breast cancer risk in
      young women.

PMID- 16284493
TI  - Monitoring the decrease in breast cancer mortality in Europe.
AB  - Trends in mortality from breast cancer over the period 1970-2000 were analysed
      for 38 European countries and the European Union (EU). Age-standardized mortality
      rates were computed by the direct method, and joinpoint analysis was used to
      identify significant changes in rates. A favourable pattern in breast cancer
      mortality in the 25 countries of the EU (as defined in May 2004) was observed
      after 1989, leading to a fall in overall rates from 21.3/100,000 in 1990 to 18.9
      in 2000. The annual percentage change in the EU was -2.1% between 1995 and 2000.
      Most northern European countries, including several Scandinavian countries and
      the UK, but also some central and southern European countries like Germany,
      Poland, the Czech Republic, Austria, Switzerland, Italy and Spain showed
      appreciable falls in rates (i.e. between 8 and 19% in the last 5 calendar years).
      The declines were larger below age 50, approaching 20% in several countries. The
      falls were smaller in France, Greece, Portugal and most eastern European
      countries. In the Russian Federation, all-age breast cancer mortality increased
      from 16.1 to 17.3/100,000 (+7.5% over the last 5 calendar years). These patterns
      reflect converging trends in breast cancer rates across Europe, which can be
      related to the more uniform reproductive and lifestyle habits. The fall in breast
      cancer mortality observed in most European countries over the last decade has to
      be attributed to earlier detection and improved treatment, although the definite
      reasons for the different trends in various countries remain at least in part
      unclear.

PMID- 16284495
TI  - Trends in cervical cancer incidence--Indian scenario.
AB  - Cancer of the uterine cervix is the second most common cancer among women in the
      world after breast cancer. It is the most common cancer among Indian women. The
      present communication reports the trends in the incidence rate of cervical cancer
      for the Indian population. The data published in Cancer Incidence in Five
      Continents for various Indian registries for different periods and/or publication
      by the individual registry served as the source material. During the years 1990
      1997, the age-adjusted incidence rates (AAR) for cervical cancer varied from 10.9
      to 65.4 amongst various registries. The highest incidence was noted in the
      Ambillikai registry. The age-specific incidence rates (ASIR) for cervical cancer
      revealed that the disease increases from 35 years and reaches a peak between the
      ages 55 to 64 years. The trend analysis by period showed a decreasing trend in
      the incidence rate of cervical cancer in all the registries. However, the
      decrease was very small. The mean annual percentage decrease in the AAR ranged
      from 0.9 to 2.6% amongst various registries. Analysis of the data by ASIR
      revealed that the mean annual percentage decrease was higher for women in earlier
      age groups in most of the registries. For women beyond 64 years, the disease
      incidence showed an increasing trend or minimal decrease. It was also noted that
      most of the cervical cancer cases were detected with regional spread of the
      disease and a very small proportion were diagnosed at a localized stage. In
      India, an organized mass-screening programme with Pap smear for early detection
      of cervical cancer is not in practice. The data suggest an urgent need for
      initiation of community screening and educational programmes for the control and
      prevention of cervical cancer.

PMID- 16284494
TI  - Age of uptake of early cancer detection facilities by low-risk and high-risk
      patients with familial breast and ovarian cancer.
AB  - INTRODUCTION: Some 5-10% of all cases of breast cancer and ovarian cancer have a
      hereditary genesis. In the setting of an interdisciplinary cancer genetics
      clinic, a study of the age at which patients first take advantage of early cancer
      detection (ECD) facilities was conducted in order to assess the influence of
      familial risk on health issues. METHODS: The study included 556 women who
      fulfilled the inclusion criteria (IC) for genetic analysis of the BRCA1 and BRCA2
      genes, as well as 205 who did not meet these criteria but attended the primary
      consultation. RESULTS: Consulters who met the inclusion criteria took advantage
      of nearly all methods of ECD at an earlier time than women who did not. A
      comparison of consulters with or without breast cancer showed that those without
      breast cancer participated in all methods of ECD at an earlier time. CONCLUSION:
      Methods of improving and increasing participation in ECD facilities, and of
      encouraging women who are at risk to start on such programs at a younger age,
      need to be discussed. In this study, familial risk already resulted in a younger
      age of uptake of ECD facilities.

PMID- 16284496
TI  - Awareness of general and personal risk factors for uterine cancer among healthy
      women.
AB  - Participation rates in gynaecological cancer screening are influenced by
      different factors. The knowledge of general and personal risk factors for uterine
      cancer among women might influence their interest in gynaecological cancer
      screening. Two thousand nine hundred women in 23 gynaecological outpatient
      services were invited to answer a structured questionnaire regarding general and
      personal risk factors for cervical and endometrial carcinoma; 2108 women
      participated. Women with a history of cancer were excluded from the study. It was
      found that levels of knowledge about uterine carcinoma were low. Only 47.4% of
      women knew the difference between the sites of origin of cervical and endometrial
      cancer. Seventy-seven per cent of participants assessed their knowledge about
      uterine malignancies as insufficient; 96.3% would appreciate more information
      about uterine cancer. Younger women were significantly less well informed than
      postmenopausal women. Known risk factors such as smoking or human papillomavirus
      (HPV) infection as factors for cervical cancer were underestimated; most women
      assessed genetic factors as most important for the development of uterine cancer.
      The level of information about risk factors as well as general facts about
      gynaecological cancer in women is low. Ameliorating this lack of information
      might influence the perception of uterine cancer and result in higher
      participation rates in gynaecological cancer screening.

PMID- 16284497
TI  - Oral lichenoid contact reactions may occasionally transform into malignancy.
AB  - The purpose was to identify cases of squamous cell carcinoma (SCC) of the tongue,
      in which a biopsy taken at the site preceding the cancer could be verified to
      show a lichenoid contact type of reaction (LCR). We retrieved all 724 SCC of the
      tongue from the Swedish Cancer Registry in the period 1995-2000. These cases were
      cross-searched with our own oral biopsy data files from 1988 to 1994, in order to
      identify biopsies with LCR-type lesions preceding the cancer. We found four
      verified and some additional tentative cases. The study demonstrated that there
      is a low incidence of malignant transformation in LCR-type oral lesions, not much
      different from what has been previously reported in oral lichen planus.

PMID- 16284498
TI  - Childhood leukaemia, polymorphisms of metabolism enzyme genes, and interactions
      with maternal tobacco, coffee and alcohol consumption during pregnancy.
AB  - Metabolic polymorphisms may influence the risk of childhood leukaemia related to
      maternal tobacco, coffee or alcohol consumption. The data were extracted from a
      case-control study including 280 cases of acute leukaemia and 288 controls. Blood
      sampling was obtained for a representative subset of 219 cases and 105 controls.
      Gene-environment interactions were estimated using both case-control and case
      only analyses. The polymorphisms of CYP1A1, GSTM1, GSTP1, GSTT1 and NQO1 were not
      associated with the risk of leukaemia. The slow EPHX1 allele was negatively
      associated with childhood leukaemia while an inverse non-significant association
      was observed with the fast EPHX1 allele. Maternal smoking during pregnancy was
      not related to leukaemia, but an interaction was observed in the case-only
      analysis with CYP1A1*2A variant allele (odds ratio (OR) 2.2 [1.0-4.9]) and with
      GSTM1 deletion (OR 2.3 [1.2-4.4]). Conversely, coffee drinking interacted
      negatively with NQO1 polymorphism in the case-only analysis (OR 0.6 [0.3-1.2] and
      0.4 [0.1-1.0] for light and heavy coffee consumptions, respectively). This study
      suggests that maternal smoking may be a risk factor for leukaemia in children who
      carry CYP1A1 or GSTM1 genotypes, which might increase reactive metabolites of
      polycyclic aromatic hydrocarbons.

PMID- 16284499
TI  - Old age as colorectal screening problem.

PMID- 16284500
TI  - Social interaction with dogs.

PMID- 16284501
TI  - A review of the Holden-Mertz criteria for critical oxygen transmission.
AB  - PURPOSE: Holden and Mertz established the foundations for the new generation of
      silicone hydrogel contact lenses for daily and extended wear in 1984. Absence of
      lens-induced corneal swelling was their premise and although this was possible
      with daily wear, the goal with extended wear seemed almost impossible because of
      the limitation of hydrogel materials. Experience with extended and daily wear of
      disposable contact lenses during the last 2 decades and, more recently, with
      silicone hydrogels has led to the reconsideration of the validity of the findings
      of Holden and Mertz. RESULTS: A pivotal influence on the Holden and Mertz
      critical Dk/t value for closed-eye lens wear was exerted by two numbers: the no
      lens wear corneal edema level (4%) and the silicone lens data point (Dk/t of
      182x10, closed-eye edema level of 2.6%). Subsequent publications appear to give a
      more accurate assessment of the no-lens closed-eye corneal edema level, and there
      are also more recent measurements of silicone hydrogel lens Dk/t and corneal
      edema responses. CONCLUSIONS: It now appears that the Holden and Mertz criteria
      for extended-wear critical Dk/t should be revised upwards to at least 125x10.

PMID- 16284502
TI  - Contact lens management of aniseikonia and photophobia induced by trauma.
AB  - PURPOSE: To describe a case of a contact lens fitting to relieve aniseikonia and
      photophobia resulting from trauma. METHODS: A 61-year-old man suffered a blunt
      injury to his left eye resulting in glaucoma and a traumatic cataract with a
      fixed pupil and iris defects. A vitrectomy, lensectomy, and iris repair were
      performed leaving him with significant anisometropia. RESULTS: The patient was
      fitted with a prosthetic contact lens. CONCLUSIONS: Contact lenses can provide
      significant visual improvement in cases of aniseikonia and photophobia.

PMID- 16284503
TI  - Pseudomonas aeruginosa keratitis in an atopic silicone hydrogel lens wearer with
      rosacea.
AB  - PURPOSE: This case report documents Pseudomonas aeruginosa corneal infection
      associated with daily wear of a silicone contact lens in a patient who also had
      bilateral, preexisting biomicroscopic findings of ocular rosacea, seborrheic
      blepharitis, keratoconjunctivitis sicca, and chronic punctate corneal
      epitheliopathy. CONCLUSIONS: Collectively, these problems produce increased risk
      of infection for wear of any contact lens; and underscore the importance of
      proper patient selection, education and post-fit monitoring even when hyper
      oxygen transmitting silicone hydrogels are utilized.

PMID- 16284504
TI  - Comparison of axial and tangential topographic algorithms for contact lens
      fitting after LASIK.
AB  - PURPOSE: Computerized videokeratography (CVK) has become the standard method for
      measuring the corneal curvature after refractive surgery. However, few resources
      exist on the use of CVK data for postoperative contact lens fitting, and no
      recommendations exist on the selection of the best topographic algorithm relevant
      to gas-permeable (GP) lens fitting. This study assessed the optimal use of
      topographic data to fit spherical GP contact lenses on patients who have
      undergone laser in situ keratomileusis. METHODS: A retrospective analysis of CVK
      maps from eight post-LASIK eyes fitted with spherical GP lenses was performed in
      the Contact Lens Service of the Department of Ophthalmology at Case Western
      Reserve University and University Hospitals of Cleveland. Axial and tangential
      maps from the Dicon CT 200 (version 3.50) or Humphrey Atlas (version A8)
      topographer were analyzed. Averaged dioptric curvatures from different locations
      (inferior, superior, and temporal) at various distances (2.0 mm, 2.5 mm, 3.0 mm,
      3.5 mm, and 4.0 mm) from the vertex normal of each eye were compared with the
      base curves of the prescribed GP contact lenses. RESULTS: One-way analysis of
      variance, Pearson correlation analysis, and paired t tests showed that the best
      topographic predictors of a successful GP base curve were the average curvatures
      at the 4.0 mm distance on the axial maps (r=0.8078, P=0.05) and at the 2.0 mm
      distance on the tangential maps (r=0.9738, P=0.0002). The mean dioptric powers of
      the GP base curve, axial map 4.0 mm curvature, and tangential map 2.0 mm
      curvature were 41.50 diopters (D), 42.65 D, and 42.67 D, respectively.
      CONCLUSION: To simplify and guide GP fitting after LASIK, the average dioptric
      curvature 4.0 mm from the vertex normal on axial maps or 2.0 mm from the vertex
      normal on tangential maps are the best predictors of accurate GP base curve
      selection.

PMID- 16284505
TI  - Three-year follow-up of biomicroscopy signs and refractive status in patients
      wearing lotrafilcon A lenses.
AB  - PURPOSE: To report the wearer experience, biomicroscopy signs, and stability of
      refractive error after 3 years' use of lotrafilcon A lenses. METHODS: Seventy
      four subjects from a multicenter clinical trial with lotrafilcon A lenses were
      queried on aspects of lens wear. Biomicroscopy signs and refractive error were
      compared to baseline measurements. RESULTS: A total of 66% of subjects reported
      continuing to wear lotrafilcon A lenses, usually for more than 21 nights, with
      high satisfaction. Signs of limbal, palpebral, and bulbar redness improved
      significantly. Average refractive error remained stable. CONCLUSIONS: Long-term
      use of lotrafilcon A lenses resulted in high wearer satisfaction, reduction of
      ocular redness, and stable refractive error.

PMID- 16284506
TI  - Therapeutic applications of lotrafilcon a silicone hydrogel soft contact lenses.
AB  - PURPOSE: To investigate the effectiveness of silicone hydrogel soft contact
      lenses for therapeutic applications. METHODS: The study included 37 patients who
      had bullous keratopathy (n=12), recurrent corneal erosion (n=9), filamentous
      keratitis (n=3), corneal melting after corneal surgery (n=4), lamellar
      lacerations (n=4), or chemical trauma (n=5) and were fitted with silicone
      hydrogel soft contact lenses between May 2000 and August 2003 in First Eye Clinic
      of Kartal Training and Research Hospital. Changes in corneal signs by slitlamp
      evaluation, judgment of pain relief, additional complications, and success of
      therapeutic lens treatment were reported. Appropriate medical therapy was given
      as required. RESULTS: A total of 83.78% of the patients had complete healing, and
      8.1% of the patients showed at least partial improvement. Visual acuity improved
      in 56% of patients, and pain relief was achieved in 91.16% of the patients. No
      additional complications were reported in relation to the lenses. CONCLUSIONS:
      The use of high-Dk lotrafilcon A soft contact lenses for therapeutic purposes is
      safe, effective, and practical.

PMID- 16284507
TI  - An investigation of the discrete and continuum models of water behavior in
      hydrogel contact lenses.
AB  - PURPOSE: To investigate the water behavior in hydrogels of differing equilibrium
      water content (EWC) and to use these results to investigate the opposing discrete
      model (thermodynamically different classes of water exist in hydrogels) and
      continuum model (water behaves as a consequence of nonequilibrium conditions) of
      nonfreezing water in swollen hydrogels. METHODS: Differential scanning
      calorimetry (DSC) was used to obtain melting thermograms for five lenses of each
      of 12 hydrogel lens types. The gravimetric content of the nonfreezing water was
      subsequently determined from an integrated endotherm for water. The effect of
      anneal time on the amount of nonfreezing water obtained in samples was
      investigated before undertaking these measurements. The glass transition
      temperature (Tg) of each of the lens types was obtained with DSC to investigate
      how the Tg was related to the amount of nonfreezing water found in the hydrogels.
      RESULTS: Melting enthalpy increased with increasing anneal time and leveled off
      at 6 hours. Low-EWC lenses showed endotherms with a single melting peak at 0
      degrees C. Materials with a higher EWC showed more complicated melting
      endotherms, with a broad shoulder occurring at temperatures below 0 degrees C.
      There was a statistically significant positive correlation between EWC and
      freezing water (R=0.95, P<0.0001), but the amount of nonfreezing water was
      similar for all lens materials. There was a statistically significant positive
      correlation between the Tg of the hydrogels and the theoretically derived weight
      fraction of nonfreezing water in the hydrogels required to bring the Tg of the
      gels down to 0 degrees C (R=0.99, P<0.0001) but not with the experimentally
      derived values (R=0.29, P=0.07). CONCLUSIONS: Low-EWC hydrogels have the lowest
      free-to-bound water ratios. That the experimentally derived values of nonfreezing
      water are different from the theoretically derived values creates doubt with the
      continuum model theory. The best model probably employs a combination of the
      discrete and continuum theories.

PMID- 16284508
TI  - Childhood onset of pterygia in twins.
AB  - PURPOSE: To report a case of childhood onset of pterygia in twins. METHODS:
      Twelve-year-old male twins had nasal lesions on the left eye of twin A and on the
      right eye of twin B. Both lesions were excised with superior conjunctival
      autograft. RESULTS: Histopathologic examination showed the lesions to be
      pterygia. Other pedigrees of familial pterygia have been described. However, to
      the authors' knowledge, this young age at onset has not been documented with
      histopathology in twins. CONCLUSIONS: This case report documents the youngest age
      at onset of pterygia in twins, with histologic confirmation. It suggests a
      genetic or developmental cause for pterygium formation.

PMID- 16284509
TI  - Assessment of the number of lamellae in the central region of the normal human
      corneal stroma at the resolution of the transmission electron microscope.
AB  - PURPOSE: To determine the total number of lamellae within the central region of
      the human corneal stroma by using a continuous section through the corneal stroma
      and at the ultrastructural resolution of the electron microscope. METHODS: Six
      human eye bank corneas, from individuals aged between 42 and 82 years, were
      received in corneal storage medium (Optisol GS) and then processed for
      transmission electron microscopy with buffered 2% glutaraldehyde fixation. Thin
      sections were mounted on parallel bar copper grids for an uninterrupted full
      corneal thickness observation. A sequence of overlapping micrographs were taken
      at 2,600x magnification, printed at a final magnification of 3,640x, and
      assembled as a montage. The number of lamellae were counted across the corneal
      stromal strip by three observers, independently, by using a preagreed set of
      criteria for identifying individual lamella. RESULTS: The average number of
      lamellae per stroma was determined to be 242+/-4 (range, 234-247). In the more
      anterior region of the stroma, the density of the lamellae was 50% greater than
      in the posterior stroma (mean, 57+/-12 per 100 microm anteriorly vs. 38+/-5 per
      100 microm posteriorly). Interobserver differences were modest and generally less
      than the intersample variance. CONCLUSIONS: When assessed at the resolution of
      the transmission electron microscope, the number of stromal lamellae in the
      central region of the human cornea are higher (at approximately 240 per cornea)
      than most previous estimates reported from light microscopy studies.

PMID- 16284510
TI  - Gaze-induced Descemet's folds secondary to a primary pterygium.
AB  - PURPOSE: To report a case of gaze-induced Descemet's folds secondary to a primary
      pterygium. METHODS: Interventional case report, chart review, and literature
      review. RESULTS: Slitlamp examination of a 49-year-old man showed Descemet's
      folds in the left eye on extreme right gaze secondary to the restrictive effect
      of a primary pterygium. The folds correlated with increasing astigmatism
      documented on corneal topography and restricted ocular motility and diplopia on
      attempted adduction. CONCLUSIONS: To the authors' knowledge, this is the first
      reported case of folds induced in Descemet's membrane secondary to the tethering
      effect of a primary pterygium.

PMID- 16284511
TI  - Flammability of common ocular lubricants in an oxygen-rich environment.
AB  - PURPOSE: Approximately 100 surgical fires take place in the United States each
      year. Recently, an ophthalmic lubricant was blamed for burning a child's eye
      while oxygen was administered during surgery. This study sought to determine
      whether four common ocular lubricants would ignite and sustain combustion in an
      oxygen-rich or standard room air environment. METHODS: A model head was modified
      to allow placement of a cow eye and marked with 1-inch gradations from the eye. A
      nasal cannula supplied room air and 100% oxygen at flow rates of 0, 2, 4, and 6
      L/minute. Four common ocular lubricants were chosen and placed on the eye before
      attempted ignition. The ignition source (an AccuTemp disposable electrocautery
      unit and unipolar and bipolar cautery set at 10, 20, and 30 watts) was brought
      down from the hairline toward the cannula. Each lubricant was tested with each
      ignition source and each room air/oxygen flow rate. RESULTS: None of the ocular
      lubricants ignited under any of the experimental environments tested. A small
      surface flame was noted with the AccuTemp electrocautery unit, but it did not
      create a flash fire during the experiment. CONCLUSIONS: The ocular lubricants in
      this experiment showed no detectable tendency to ignite, even with direct
      application of the ignition source. Factors such as body hair or oxygen pooling
      likely provided the conditions necessary for the surgical fire. Most importantly,
      the ophthalmic lubricants tested actually protected the corneal epithelium and
      decreased damage to the conjunctiva and lids.

PMID- 16284512
TI  - From the editor.

PMID- 16284513
TI  - Not-for-profit versus for-profit health care providers-Part I: comparing and
      contrasting their records.
AB  - The debate over which health care providers are most capably meeting their
      responsibilities in serving the public's interest continues unabated, and the
      comparisons of not-for-profit (NFP) versus for-profit (FP) hospitals remain at
      the epicenter of the discussion. From the perspective of available factual
      information, which of the two sides to this debate is correct? This article is
      part I of a 2-part series on comparing and contrasting the performance records of
      NFP health care providers with their FP counterparts. Although it is demonstrated
      that both NFP and FP providers perform virtuous and selfless feats on behalf of
      America's public, it is also shown that both camps are involved in potentially
      willful clinical and administrative missteps. Part I contains the background
      information (eg, legal differences, perspectives on social responsibility, and
      types of questionable and fraudulent behavior) that is necessary to adequately
      understand the scope of the comparison issue. Part II offers actual comparisons
      of the 2 organizational structures using several disparate factors such as
      specific organizational behaviors, approach to the health care priorities of cost
      and quality, and business-focused goals of profits, efficiency, and community
      benefit.

PMID- 16284514
TI  - The lost art of the covenant: trust as a commodity in health care.
AB  - Physicians argue that the advent of managed care has turned medicine into a
      business and that they spend more time learning the art of doing business than
      practicing medicine, while losing their professional spirit, patient loyalty,
      autonomy, and income. Medicine was a business before it was a science. Holding on
      to Hippocratic ideals in a world of on-demand consumers has made the covenantal
      physician-patient relationship ineffective and devoid of mutual trust. Physicians
      have argued that trust is time-dependent and a casualty of time-bound managed
      care guidelines. The author suggests that the principle of trust is not outdated,
      not exclusively time-dependent, and is still relevant to a modern Hippocrates
      loyalist. A relationship of trust is built on the style and quality of verbal and
      nonverbal communication. Trust is not an acquired trait; it is an expectation
      resulting from an interactive process of human concern and caring.

PMID- 16284515
TI  - Medicare-the development of publicly financed health insurance: Medicare's impact
      on the nation's health care system.
AB  - It is useful for health care managers to understand Medicare's history and the
      impact on providers of ever-changing Medicare payment methods. Initially,
      Medicare payments resembled those of commercial insurance plans and Blue Cross
      Blue Shield plans. When Congress became concerned about the increasing costs of
      Medicare, new payment methods were created to limit payments to providers. The
      prospective payment system, imposed on hospitals in 1987 and later on nursing
      homes, home health agencies, and other services, has been adapted by commercial
      plans, Blue Cross Blue Shield associations, and state Medicaid programs. Changes
      in payer reimbursements require health care managers to adjust the department's
      charge master and exert more control of departmental costs. The story of
      Medicare's beginnings and development can provide some insight into the
      possibility of national health insurance, given the historic and current politics
      that limit publicly financed social programs. This article discusses the
      development of Medicare and its administration and serves as an introduction to
      the complex realities of health care reimbursement policy.

PMID- 16284516
TI  - Importance x dissatisfaction = a formula for managerial action.
AB  - Management should not only survey employees about their satisfaction with an
      issue but should also inquire about how important that issue is to them. If the
      issue is very important to employees and they are very dissatisfied, then
      management action may be urgent. However, if staff members are dissatisfied with
      an issue that is unimportant to them, then no management action may be required.
      Rank ordering the items by importance and then subtracting satisfaction from
      importance to get a performance-gap score is insufficient. The decision maker
      still may have to use intuition to determine which items have priority. Rather
      than gap analysis, it is better to multiply the importance score by the
      dissatisfaction score. This will yield a clear rank order of the issues to which
      the management must attend. The authors used the multiplicative method with a
      health care organization. These results are analyzed, and management actions are
      recommended.

PMID- 16284517
TI  - Attrition in nursing: perspectives from the national survey of college graduates.
AB  - Problems with attracting and retaining nurses during a tight labor market are
      compounded by some fundamental issues related to attrition from the field. It is
      important to recognize that, of the students who graduate from nursing schools
      each year and enter the field of nursing, significant attrition occurs during the
      first 5 years in the profession
      [www.aacn.nche.edu/media/backgrounders/shortagefacts.htmaacn.nche.edu (2002)].
      This article uses data from the National Science Foundation's National Survey of
      College Graduates to examine various scenarios and possible reasons for why some
      nurses abandon their careers [www.nsf.gov/sbe/srs/snscg/start.htm (2003)]. In
      doing so, we consider entry into, and attrition from, the nursing profession at
      various stages. Using data from the National Survey of College Graduates, the
      initial evaluation suggests that, at points during the career, the individual
      confronts potential problems and issues which can lead to career attrition.

PMID- 16284519
TI  - College on the Internet.
AB  - Online degree programs are very popular. They offer health care professionals the
      opportunity to attend class at times convenient to their busy schedules. Online
      courses are different from traditional classroom courses, so health care
      professionals need to know what to expect. Managers can be a key resource to
      staff regarding returning to school and the options available.

PMID- 16284520
TI  - When your nursing student is culturally diverse.
AB  - Nursing faculty are increasingly confronted with nursing students who are
      culturally diverse. No longer can traditional educational strategies be expected
      to work with everyone, and strategies must be selected which meet the needs of
      the students. This article addresses the need to adapt to diversity in the
      classroom as well as how to personalize strategies to the needs of the students,
      plan appropriate interventions, and evaluate interventions for effectiveness. Use
      of the Giger-Davidhizar assessment model can assist the faculty in assessing for
      cultural differences and thus can provide a base on which to plan effective
      interventions.

PMID- 16284521
TI  - Escaping the box: preparing allied health practitioners for management positions.
AB  - Career ladders designed for health care practitioners are not always long enough
      to reach beyond the top rungs of clinical practice. Limited upward mobility can
      result in dissatisfaction and potential loss of experienced staff members. The
      same skills that allow practitioners to function successfully in patient care can
      be tapped into to prepare clinicians to move upward in administrative positions.
      This has already occurred successfully in the nursing profession. Managers should
      take advantage of the yearly performance evaluation to identify those health
      professionals who are interested in advancement. Using a strengths, weakness,
      opportunities, and threats analysis, the manager and clinician can work together
      to develop a developmental plan that will build on existing strengths while
      developing the less prepared areas. Managerial skill enhancement should be
      combined with mentoring from persons already filling administrative roles to
      enable the clinician to develop a network of contacts. A planned approach should
      enable interested clinicians to successfully transition from hands-on practice
      into managerial positions.

PMID- 16284522
TI  - Genesis of a professional development tool for ambulatory pediatric nursing
      practice.
AB  - The purpose of this project was to develop a system that would allow ambulatory
      pediatric nurses to describe their practice and to develop in their role as
      nurses. Patricia Benner's novice to expert philosophy has been used to describe
      the practice of nurses in many specialties; however, it has not been applied to
      ambulatory pediatric practice. A group of nurses at Children's Hospital of
      Wisconsin used Benner's philosophy to generate behaviors that evolved from the
      novice to the expert within the domains of nursing practice outlined in the
      ambulatory nurse job description. This tool has been implemented as part of the
      performance review process and is given to new nurses on orientation as a
      framework for nurses' professional development.

PMID- 16284523
TI  - Winning loyalty with a vision and a corporate soul.
AB  - This article provides insight and practical application for how to improve
      patient satisfaction and loyalty through a vision with a corporate soul. This
      article shows from actual experience that the chief executive officer must set
      the vision for the organization. The vision is key to an organization's ability
      to win loyalty. Without a vision to become great, an organization will never
      fulfill its potential to best serve its community. Essential to the vision is
      developing a corporate soul that embraces the intangibles of the human spirit of
      sensing the needs of others through meaning, purpose, empathy, caring, and
      sharing. Although recognizing that the tangibles of revenue, expenses, patient
      volume, and profit margin are necessary, addressing the intangibles is critical
      to long-term sustainability.

PMID- 16284524
TI  - Prevalence of transmitted HIV-1 drug resistance and the role of resistance
      algorithms: data from seroconverters in the CASCADE collaboration from 1987 to
      2003.
AB  - OBJECTIVES: To examine factors influencing the rate of transmitted drug
      resistance (TDR) among seroconverters, with particular emphasis on 3 widely used
      genotypic drug resistance algorithms. METHODS: The study used data from CASCADE
      (Concerted Action on Seroconversion to AIDS and Death in Europe), a collaboration
      of seroconverter cohorts in Europe and Canada. Genotypic resistance data were
      derived within 18 months of the last seronegative test or date of laboratory
      evidence of acute infection and before the initiation of antiretroviral therapy.
      The Stanford algorithm was used to analyze each individual's nucleotide sequence.
      A multivariate logistic model was used to assess independent relationships
      between the presence of TDR and exposure category, sex, age at seroconversion,
      and year of seroconversion. The paper also describes 3 alternative definitions of
      resistance: the Stanford algorithm, the key resistance mutations defined by the
      International AIDS Society, and the Agence Nationale de Recherches sur le Sida
      (ANRS) algorithm. RESULTS: Forty-five of 438 patients (10.3%) seroconverting
      between 1987 and 2003 were infected with a drug-resistant HIV-1 variant. Forty
      patients (9.1%) showed resistance mutations to only 1 class of antiretroviral
      drugs, 2 (0.5%) to 2 classes, and 3 (0.7%) to 3 classes of antiretroviral
      therapy. It was suggested that individuals seroconverting later in calendar time
      were more likely to have TDR (relative risk 3.89 and 95% CI: 0.84 to 18.02, and
      relative risk 4.69 and 95% CI: 1.03 to 21.31, for 1996-1999 and 2000-2003,
      respectively, compared with pre-1996; P trend = 0.08). This trend was apparent
      regardless of the definition of TDR used. The total estimated proportion of
      individuals with TDR varied between 10.3% and 15.5% according to which definition
      was used. CONCLUSIONS: Evidence was found for the rise of TDR over time. A
      specific definition of what constitutes TDR rather than a simple list of
      mutations is needed.

PMID- 16284525
TI  - Bioengineering lactic acid bacteria to secrete the HIV-1 virucide cyanovirin.
AB  - An urgent need exists to prevent the sexual transmission of HIV-1. With
      prevalence rates exceeding 35% in parts of sub-Saharan Africa, increasing
      attention has been placed on developing and testing microbicidal agents capable
      of preventing virus transmission at mucosal sites. HIV-1 microbicides must meet
      several requirements before their widespread use. The drugs must be able to
      neutralize a diversity of HIV-1 strains, not induce mucosal inflammation, be
      associated with minimal side effects, and be effective for a prolonged period
      after a single application. Recent work has demonstrated the utility of
      recombinant lactic acid bacteria (LAB) as agents of mucosal drug delivery. Here,
      we describe the bioengineering of strains of LAB to secrete the prototypic
      virucidal compound cyanovirin (CV-N) and demonstrate the anti-HIV-1 activity of
      secreted CV-N. Our results suggest that recombinant LAB may serve as effective
      microbicidal compounds and deserve in vivo testing in simian immunodeficiency
      virus models of mucosal virus transmission.

PMID- 16284527
TI  - Spanish HIV-1-infected long-term nonprogressors of more than 15 years have an
      increased frequency of the CX3CR1 249I variant allele.
AB  - BACKGROUND AND OBJECTIVES: The influence of the polymorphisms of the CX3CR1
      chemokine receptor gene on the natural history of HIV-1 infection is
      controversial. This study aimed to determine whether functionally active CX3CR1
      genetic variants are associated with long-term nonprogressive infection of >15
      years in HIV-1-infected Spanish patients. PATIENTS AND METHODS: Two single
      nucleotide polymorphisms, V249I (G > A) and T280M (C > T), of the CX3CR1 gene
      were assessed in 271 Spaniards. These included 60 HIV-1-infected patients who
      were long-term nonprogressors (LTNPs) of >15 years, 109 HIV-1-infected patients
      who were usual progressors (UPs), and 102 control subjects. The CCR5Delta32 was
      also assessed. Genotyping was performed using polymerase chain reaction and
      automatic sequencing analysis methods on white cell DNA. Genotype and allele
      frequencies were compared by the chi test and the Fisher exact test. RESULTS: The
      frequencies of the 249I variant allele were 42% for LTNPs, 24.5% for UPs, and 35%
      for healthy controls; the differences between LTNPs and UPs were significant
      (odds ratio 0.46; 95% CI: 0.27 to 0.75; P = 0.0017). For 280M the distribution
      was 16% for LTNPs, 14% for UPs, and 17% for healthy controls (P = NS). The
      haplotype 249I280T was significantly more common in LTNPs than in UPs (P =
      0.0007). These results persisted after excluding from the analysis the
      individuals carrying the CCR5Delta32. CONCLUSIONS: CX3CR1 249I variant allele is
      more frequent in Spanish HIV-1-infected LTNPs of >15 years. This effect is
      independent of the presence of the CCR5Delta32 allele.

PMID- 16284528
TI  - Identification of a novel HIV-1 circulating ADG intersubtype recombinant form
      (CRF19_cpx) in Cuba.
AB  - Circulating recombinant forms (CRFs) represent a substantial proportion of HIV-1
      isolates in the global pandemic. Characterization of HIV-1 genetic forms,
      including CRFs, may be relevant to studies on molecular epidemiology,
      recombination, superinfection, vaccine development, and antiretroviral therapy.
      This study analyzes near complete genomes of 4 epidemiologically unlinked viruses
      from Cuba, originally characterized as D/A intersubtype recombinants in pol and
      env segments. The genomes of 3 viruses exhibited virtually coincident mosaic
      structures, with multiple segments of subtypes A, D, and G and uniform
      phylogenetic clustering with each other along the genome. These results allow us
      to define a new CRF (CRF19_cpx). The 4th analyzed Cuban virus was recombinant
      between CRF19_cpx and CRF18_cpx (which also circulates in Cuba). CRF19_cpx
      exhibited homology to an AG intersubtype recombinant virus from Cameroon
      (CM53392) along approximately 5 kb and clustered with a subtype D virus from
      Gabon (G109) in gag. Four other viruses from central or west Africa were also
      phylogenetically related to CRF19_cpx in env fragments. These results allow us to
      define CRF19_cpx as a second novel CRF of African origin circulating in Cuba, to
      identify putative representative viruses of its parental strains, and to
      characterize a unique CRF18/CRF19 recombinant virus.

PMID- 16284526
TI  - Risk for HIV-1 infection associated with a common CXCL12 (SDF1) polymorphism and
      CXCR4 variation in an African population.
AB  - CXC chemokine ligand 12 (CXCL12), or stromal cell-derived factor 1 (SDF1), is the
      only known natural ligand for the HIV-1 coreceptor, CXC chemokine receptor 4
      (CXCR4). A single nucleotide polymorphism (SNP) in the CXCL12 gene (SDF1-3'A) has
      been associated with disease progression to AIDS in some studies, but not others.
      Mutations in the CXCR4 gene are generally rare and have not been implicated in
      HIV-1/AIDS pathogenesis. This study analyzed the SDF1-3'A SNP and performed
      mutation screening for polymorphic markers in the CXCR4 gene to determine the
      presence or absence of significant associations with susceptibility to HIV-1
      infection. The study consisted of 257 HIV-1-seropositive patients and 113 HIV-1
      seronegative controls representing a sub-Saharan African population belonging to
      the Xhosa ethnic group of South Africa. The SDF1-3'A SNP was associated with an
      increased risk for HIV-1 infection (P = 0.0319) whereas no significant
      association was observed between the occurrence of the SDF1-3'A SNP and increased
      or decreased plasma levels of CXCL12. Comprehensive mutation analysis of the
      CXCR4 gene confirmed a high degree of genetic conservation within the coding
      region of this ancient population.

PMID- 16284529
TI  - HIV infection does not affect the performance of noninvasive markers of fibrosis
      for the diagnosis of hepatitis C virus-related liver disease.
AB  - BACKGROUND: Noninvasive markers of hepatic fibrosis hold great promise to stage
      liver fibrosis and to monitor disease progression. To date, few studies have
      assessed the performance of the currently available markers of hepatic fibrosis
      in HIV-infected cohorts. The aim of the current study was to compare the
      diagnostic performance and characteristics of a number of noninvasive markers of
      hepatic fibrosis in populations of hepatitis C virus (HCV)-infected patients with
      and without HIV infection. METHODS: A sample of 97 subjects (40 HCV/HIV
      coinfected, 57 HCV-infected) undergoing liver biopsy as part of an ongoing
      prospective cohort study was evaluated. Liver biopsies were assessed by a single
      hepatopathologist and scored according to Ishak criteria. Noninvasive markers of
      fibrosis studied included international normalized ratio, platelet count,
      aspartate aminotransferase (AST)/alanine aminotransferase ratio, AST platelet
      ratio index (APRI), Forns index, procollagen III N peptide, hyaluronic acid, and
      YKL-40. RESULTS: The correlations between fibrosis markers with the stage of
      fibrosis and the diagnostic performance of each of the tests were similar in the
      groups with and without HIV infection. Although a trend to improved diagnostic
      performance in the HCV/HIV-coinfected group was observed, this may be related to
      the small sample size. CONCLUSIONS: The diagnostic performance of the evaluated
      noninvasive markers of liver fibrosis is equivalent in HCV/HIV-coinfected and HCV
      infected subjects. These tests may be of value for the clinical evaluation of
      HCV/HIV-coinfected patients and warrant further study.

PMID- 16284530
TI  - Effectiveness of short-term and long-term zidovudine prophylaxis on detection of
      HIV-1 subtype E in human placenta and vertical transmission.
AB  - Antiretroviral treatment with zidovudine (ZDV) from the 14th week until the end
      of pregnancy has markedly reduced the vertical transmission rate of HIV-1 in
      Europe and North America. A shorter duration of treatment has reduced this rate
      in Africa and Southeast Asia to a lesser degree. In Southeast Asia, subtype E is
      the major subtype rather than subtype B as in Western countries. The goals of
      this study were to determine the optimal duration of ZDV prophylaxis for subtype
      E and to confirm its effectiveness at the histologic level. Fifty pregnant women
      seropositive for HIV-1 subtype E were given ZDV prophylaxis consisting of 300 mg
      administered twice daily, switching to 300 mg administered every 3 hours from the
      onset of labor until delivery. Twenty-seven received "short-term" ZDV lasting 14
      to 35 days before delivery, whereas the other 23 received "long-term" ZDV lasting
      62 to 92 days. The effectiveness of ZDV prophylaxis was assessed by detection of
      HIV-1 in the placenta using in situ polymerase chain reaction (PCR). All babies
      in this study were tested up to one year of age. Three were not positive until
      after one month of age, but one was positive as a neonate. Four neonates were
      positive for HIV-1 as detected by PCR on peripheral blood, including one in the
      neonatal period. All cases were from the short-term prophylaxis group. Decidual
      glandular epithelial cells were the only cell type in the placenta that expressed
      HIV proviral DNA under ZDV prophylaxis. Sixty-seven percent of placentas in the
      short-term ZDV group showed more than occasional positive cells compared with 22%
      in the group receiving long-term ZDV prophylaxis (P < 0.02). This is first study
      to compare the effectiveness of short-term and long-term ZDV prophylaxis with
      respect to the presence of HIV in the placenta. Our study shows that longer (at
      least 60 days) prophylaxis is more effective in reducing HIV expression in the
      placenta and is associated with reduced transmission to neonates.

PMID- 16284531
TI  - The Chilean AIDS cohort: a model for evaluating the impact of an expanded access
      program to antiretroviral therapy in a middle-income country--organization and
      preliminary results.
AB  - Chile, middle-income country with 15 million people, began an expanded access
      program (EAP) to antiretroviral therapy (ART) in 2001. EAP provides ART,
      monitoring, and funding for management of associated complications in 32 points
      of care. A national cohort (Chilean AIDS Cohort [ChiAC]), enrolling 98% of these
      patients, was created for standardized treatment and impact evaluation.
      Information exchange is mainly through the Internet. By December 2004, the ChiAC
      had 4365 participants (83.3% male). At baseline, 47.5% had clinical AIDS, 26.2%
      were asymptomatic, 80.2% had a CD4 count <200 cells/mm and 58.2% were ART naive;
      in these patients, the most frequent regimen is zidovudine, lamivudine, and
      efavirenz. A 6-month follow-up in 1057 patients showed a global mortality of 5%
      (0.5% if patients were asymptomatic at baseline and 8.3% if patients had baseline
      AIDS). There was a similar risk of death if the baseline CD4 count was 100 to 200
      cells/mm or >200 cells/mm ( approximately 1%), but this increased to 4.8%
      (relative risk [RR] = 5.2) and 10.7% (RR = 11.5) if the CD4 count was 51 to 100
      cells/mm or <or=50 cells/mm, respectively. Discontinuation occurred in 7.7% of
      patients because of drug toxicity, and progression occurred in 2.9%. A successful
      EAP to ART with the resources of a middle-income country is possible. Early
      results are similar to those of industrialized countries. A national cohort
      allows better implementation and evaluation of the program and may be a useful
      model for other countries.

PMID- 16284532
TI  - High proportion of T-cell systemic non-Hodgkin lymphoma in HIV-infected patients
      in Lima, Peru.
AB  - OBJECTIVE: Few reports have described the clinical and pathologic characteristics
      of HIV-related systemic non-Hodgkin lymphoma (sNHL) in developing countries. We
      aimed to determine these characteristics from a national HIV reference center in
      Peru and to evaluate factors associated with survival. METHODS: A
      retrospective/prospective study of patients with HIV-related sNHL from the
      Guillermo Almenara General Hospital in Lima, Peru between 1993 and 2004. Clinical
      characteristics at diagnosis included age, gender, risk behavior, previous AIDS
      diagnosis, opportunistic diseases, previous highly active antiretroviral therapy,
      Karnofsky score, origin, clinical stage and B-cell symptoms of sNHL, and CD4 cell
      count. Cases of sNHL were classified according to the criteria of the World
      Health Organization. RESULTS: Thirty-three cases were identified (26 male, age
      range: 38 +/- 10 years). Ten patients (30%) had a prior history of AIDS, 14 (42%)
      had a Karnofsky score of <or=70, and 18 (56%) had clinical stage IV sNHL. The CD4
      cell count median value was 111 cells/microL (n = 25). Twenty-four cases (73%)
      were B-cell sNHL, and 9 cases (27%) were T-cell sNHL, both from peripheral cells.
      Nineteen cases of sNHL were extranodal: 15 of B-cell origin and 4 of T-cell
      origin. Eighteen cases of B-cell sNHL had diffuse large cell histologic findings,
      and all cases of T-cell sNHL were unspecified. Although there were no significant
      differences in clinical characteristics between phenotypes, patients with T-cell
      sNHL had less aggressive disease and a better survival rate. CONCLUSIONS: A high
      proportion of T-cell sNHL cases was found at an HIV reference center in Peru.
      Clinical characteristics were similar between B-cell and T-cell lymphoma
      patients. T-cell lymphoma was less aggressive, and patients with T-cell lymphoma
      had a better survival rate than those with B-cell lymphoma.

PMID- 16284534
TI  - Prednisolone pharmacokinetics in the presence and absence of ritonavir after oral
      prednisone administration to healthy volunteers.
AB  - Corticosteroid therapy has been associated with bone toxicities (eg,
      osteonecrosis) and Cushing syndrome in HIV-infected patients; this may be
      partially attributable to a pharmacokinetic drug interaction between HIV protease
      inhibitors and corticosteroids. The purpose of this study was to characterize the
      influence of low-dose ritonavir on prednisolone pharmacokinetics in healthy
      subjects. Ten HIV-seronegative volunteers were given single oral doses of
      prednisone, 20 mg, before (baseline) and after receiving ritonavir, 200 mg, twice
      daily for 4 and 14 days. After each prednisone dose, serial blood samples were
      collected and prednisolone concentrations were determined; pharmacokinetic
      parameter values were compared between the groups. Geometric mean ratios (GMRs,
      90% confidence interval [CI]) of the prednisolone area under the plasma
      concentration versus time curve (AUC0-infinity) after 4 and 14 days of ritonavir
      versus baseline were 1.41 (90% CI: 1.08 to 1.74) and 1.30 (90% CI: 1.09 to 1.49),
      respectively (P = 0.002 and P = 0.004, respectively). GMRs of prednisolone
      apparent oral clearance (Cl/F) were 0.71 (09% CI: 0.57 to 0.93) and 0.77 (90% CI:
      0.67 to 0.92) after 4 and 14 days of ritonavir versus baseline, respectively (P =
      0.0004 and P = 0.0003, respectively). Ritonavir significantly increased the
      systemic exposure of prednisolone in healthy subjects. Results from this
      investigation suggest that corticosteroid exposure is likely elevated in HIV
      infected patients receiving protease inhibitors.

PMID- 16284533
TI  - Assessment of adipokine expression and mitochondrial toxicity in HIV patients
      with lipoatrophy on stavudine- and zidovudine-containing regimens.
AB  - OBJECTIVES: Despite evidence for the role of adipokines such as adiponectin in
      the metabolic toxicities of protease inhibitor (PI)-treated patients, little is
      known about their role in nucleoside reverse transcriptase inhibitor (NRTI)
      induced lipoatrophy (LA). We analyzed the relations between mitochondrial
      toxicity, adipokine expression, and clinical LA in peripheral blood mononuclear
      cells (PBMCs) and adipose samples from individuals treated with stavudine (d4T)
      or zidovudine (ZDV) in comparison to patients undergoing highly active
      antiretroviral therapy (HAART) as well as HIV-negative individuals. METHODS: In
      this cross-sectional analysis, we studied 18 PI-naive HIV-infected patients with
      LA treated with d4T (d4T+LA+ [n = 12]) or zidovudine (ZDV+LA+ [n = 6]) in
      comparison to HAART-treated patients with (HAART+LA+ [n = 8]) and without
      (HAART+LA- [n = 8]) LA as well as HIV-negative controls (n = 12). Adipose samples
      were assessed for protein and/or messenger RNA (mRNA) levels of adiponectin,
      tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-6, and sterol regulatory
      element-binding protein (SREBP) 1a/c in all groups, whereas adipose and PBMC
      samples from the d4T+LA+, ZDV+LA+, and HIV-negative subgroups were assessed for
      mitochondrial DNA (mtDNA) depletion and cytochrome c-oxidase (COX) II/COX IV
      ratios. RESULTS: There was no change in mtDNA levels in adipose or PBMC samples
      in NRTI-treated patients with LA, although patients treated with d4T had reduced
      COX II/COX IV ratios in adipose and PBMC samples. Adipose tissue adiponectin mRNA
      and plasma levels were reduced in the d4T- and ZDV-treated patients regardless of
      the use of PIs. Tissue SREBP1c mRNA levels were also significantly reduced in
      both NRTI groups when compared with the HIV-negative controls. Significant
      reductions in SREBP1c levels were also evident with the HAART+LA+ group when
      compared with HAART+LA- controls. CONCLUSIONS: Patients with LA on d4T-based
      regimens show evidence of mitochondrial respiratory chain dysfunction, whereas
      the d4T- and ZDV-based regimens also demonstrated reduced SREBP1c and adiponectin
      levels, findings that have previously been shown with PIs.

PMID- 16284536
TI  - HIV-1 infection prevalence and incidence trends in areas of contrasting levels of
      infection in the Kagera region, Tanzania, 1987-2000.
AB  - This study aimed at assessing the extent to which decline in HIV infection
      prevalence reflects decline in incidence in 3 areas with contrasting initial
      exposure to the HIV epidemic in the Kagera region of Tanzania. A population
      sample was recruited for the baseline study in 1987 through a multistage cluster
      sampling technique to determine HIV prevalence. Seronegative individuals
      identified in the baseline and subsequent studies were followed up for 3 years to
      yield trends in incidence that were compared for the 3 areas. The overall age
      adjusted HIV-1 prevalence in the high-prevalence area of Bukoba urban declined
      significantly from 24.2% in 1987 to 18.2% in 1993 and later to 13.3% in 1996 (P =
      0.0001). In the medium-prevalence area of Muleba, overall age-adjusted prevalence
      declined significantly from 10.0% in 1987 to 6.8% in 1996 and later to 4.3% in
      1999 (P = 0.0003), whereas in the low-prevalence area of Karagwe the prevalence
      declined from 4.5% in 1987 to 2.6% in 1999 (P = 0.01). In all 3 areas, the most
      significant decline was consistently observed among women in the age group 15-24
      years. No age group exhibited a significant upward prevalence trend. The HIV-1
      incidence for Bukoba urban declined from 47.5 to 9.1 per 1000 person-years of
      observation in 1989 and 1996, respectively, whereas in Muleba it decreased from
      8.2 to 3.9 in 1989 and 2000, respectively. Sex-specific estimates indicated a
      significant decline among women in the high-prevalence area of Bukoba urban from
      51.5 to 9.2 per 1000 person-years at risk (P = 0.001). It is concluded that the
      HIV-1 epidemic in Kagera is on the decrease as reflected by the decline in HIV-1
      incidence and prevalence trends particularly among the 15-24 year olds. The
      decline in the 3 areas of differing magnitude implies that the HIV/AIDS epidemic
      may be arrested early without necessarily peaking to saturation levels.

PMID- 16284535
TI  - Increased circulating interleukin-7 levels in HIV-1-infected women.
AB  - Sex-based differences in CD4 T-cell (CD4) counts are well recognized, but the
      basis for these differences has not been identified. Conceivably, homeostatic
      factors may play a role in this process by regulating T-cell maintenance and
      repletion. Interleukin (IL)-7 is essential for normal T-cell production and
      homeostasis. We hypothesized that differences in IL-7 might contribute to sex
      based differences in CD4 counts. Circulating IL-7 levels were analyzed in 299 HIV
      1-infected women and men. Regression analysis estimated that IL-7 levels were 40%
      higher in women than in men (P = 0.0032) after controlling for CD4 count, age,
      and race. Given the important role of IL-7 in T-cell development and homeostasis,
      these findings suggest that higher IL-7 levels may contribute to higher CD4
      counts in women.

PMID- 16284537
TI  - Behavioral and social issues among volunteers in a preventive HIV vaccine trial
      in Thailand.
AB  - Behavioral and social issues were investigated in 363 phase I/II preventive HIV-1
      vaccine trial volunteers in Thailand. These issues included risk behavior, HIV
      knowledge, distress, and social consequences of vaccine trial participation. Data
      were collected at baseline and at 4-, 8-, and 12-month follow-up visits.
      Volunteers reported relatively low levels of risk behaviors at baseline and at
      follow-up. Overtly negative reactions from family or friends were reported by
      5.9%. No experiences of discrimination in employment, health care, or insurance
      were reported. Mean levels of distress were low throughout the trial, and HIV
      related knowledge was high, although it was common to consider the possibility of
      HIV transmission through casual contact. Findings add to the evidence that
      preventive HIV vaccine trials are feasible in Thailand.

PMID- 16284539
TI  - Hospitalizations for metabolic conditions, opportunistic infections, and
      injection drug use among HIV patients: trends between 1996 and 2000 in 12 states.
AB  - BACKGROUND: Rapid changes in HIV epidemiology and highly active antiretroviral
      therapy (HAART) may have resulted in recent changes in patterns of inpatient
      utilization. OBJECTIVE: To examine trends in inpatient diagnoses and mortality in
      HIV patients. DESIGN/SETTING/PATIENTS: Serial cross-sectional analyses of HIV
      patients hospitalized in 1996, 1998, and 2000, using hospital discharge data from
      the Healthcare Costs and Utilization Project for 12 states. Each hospitalization
      was classified as an opportunistic illness, complication of injection drug use
      (IDU), liver-related complication, ischemic heart disease, cerebrovascular
      disease, non-Pneumocystis carinii pneumonia (PCP), diabetes, or chronic hepatitis
      C virus (HCV). MAIN OUTCOME MEASURES: Number of hospital admissions, inpatient
      mortality. RESULTS: We evaluated 316,963 admissions that occurred between 1996
      and 2000, with an overall mortality of 7%. Hospitalizations for opportunistic
      infections significantly decreased from 40% to 27% of all HIV-related admissions.
      The overall proportion of IDU complications remained relatively stable (6%) each
      year. Hospitalizations increased for liver-related complications from 8% to 13%
      and for chronic HCV from 1% to 5% in this period. The number of hospitalizations
      for cerebrovascular disease and for ischemic heart disease was relatively
      negligible in all years. Overall, inpatient mortality decreased between 1996 and
      2000. Relatively higher mortality was observed among African Americans,
      Hispanics, those with Medicaid, those with Medicare, and the uninsured, however.
      Opportunistic infections and liver-related complications were associated with
      greater inpatient mortality. CONCLUSION: Results do not show a significant recent
      rise in HIV-related inpatient utilization. Admissions to treat opportunistic
      infections have declined precipitously, consistent with the effects of HAART.
      Although not dramatic, liver-related disease is an increasing cause of
      hospitalization in HIV+ patients.

PMID- 16284538
TI  - Acceptability of exclusive breast-feeding with early cessation to prevent HIV
      transmission through breast milk, ANRS 1201/1202 Ditrame Plus, Abidjan, Cote
      d'Ivoire.
AB  - OBJECTIVE: We assessed the uptake of a nutritional intervention promoting
      exclusive breast-feeding with early cessation between 3 and 4 months of age to
      reduce postnatal transmission of HIV in Abidjan, Cote d'Ivoire. DESIGN: Between
      March 2001 and March 2003, HIV-infected pregnant women who had received perinatal
      antiretroviral prophylaxis were systematically offered prenatally 2 infant
      feeding interventions: artificial feeding or exclusive breast-feeding during 3
      months and then early cessation of breast-feeding. Mother-infant pairs were
      closely followed for a period of 2 years, with continuous nutritional counseling
      and detailed collection of feeding practices. RESULTS: Among the 557 mothers
      enrolled, 262 (47%) initiated breast-feeding. Of these women, the probability of
      practicing exclusive breast-feeding from birth was 18% and 10% at 1 and 3 months
      of age, respectively. Complete cessation of breast-feeding was obtained in 45%
      and 63% by 4 and 6 months of age, respectively. Environmental factors such as
      living with a partner's family were associated with failure to initiate early
      cessation of breast-feeding. CONCLUSIONS: Acceptability of exclusive breast
      feeding was low in this urban population. Shortening the duration of breast
      feeding seemed to be feasible, however. Further investigations are ongoing to
      evaluate the safety and effectiveness of this intervention in reducing breast
      milk HIV transmission.

PMID- 16284540
TI  - Assessing the attitudes, knowledge, and awareness of HIV vaccine research among
      adults in the United States.
AB  - OBJECTIVES: To assess HIV vaccine research attitudes, awareness, and knowledge
      among adults in the general US population, African Americans, Hispanics, and men
      who have sex with men (MSM). METHODS: Applying results of focus groups and a
      media content analysis, a survey was designed and conducted to validate key HIV
      vaccine research themes and messages identified by focus groups and a media
      content analysis. Between December 2002 and February 2003, 3509 telephone
      interviews were conducted, including 2008 randomly selected from the general
      population, and 501 population-specific samples of African Americans and
      Hispanics, and 500 from MSM. RESULTS: Although the majority of each population
      believes that an HIV preventive vaccine is the best way to control and end the
      global AIDS epidemic, only 34.9% of African Americans and 28.8% of the general
      population are supportive of someone they know volunteering for an HIV vaccine
      trial. The study also found that 47.1% of African Americans, 26.5% of Hispanics,
      and 13.4% of MSM believed an HIV vaccine already exists and is being kept secret,
      and 78.0% of African Americans, 57.5% of Hispanics, and 68.0% of MSM did not know
      or incorrectly believed that the vaccines being tested could cause HIV infection.
      A subanalysis of the general population also found that women generally had less
      knowledge of or a decreased awareness about HIV vaccine research. CONCLUSIONS:
      Awareness, knowledge, and attitudes toward HIV vaccine research vary by
      population and these issues must be addressed to ensure an adequate number of
      volunteers for future domestic HIV preventive vaccine clinical trials. In some
      populations, barriers such as misinformation and distrust must be targeted to
      increase support for HIV vaccine research.

PMID- 16284541
TI  - Increased risk of tuberculosis with human T-lymphotropic virus-1 infection: a
      case-control study.
AB  - OBJECTIVES: To investigate whether infection with human T-lymphotropic virus type
      1 (HTLV-1) increases the risk of tuberculosis. DESIGN: A case-control study.
      SETTING: City of Salvador, Brazil. PARTICIPANTS: A total of 375 patients with
      tuberculosis (cases) and 378 individuals without tuberculosis (controls), matched
      by age and sex. MAIN OUTCOME MEASURE: Tuberculosis of lung or lymph node. MAIN
      EXPOSURE: Human HTLV-1 infection. RESULTS: The prevalence of HTLV-1 infection was
      4.27% (16/375) in patients with tuberculosis and 1.32% (5/378) in controls,
      resulting in a crude odds ratio of 3.31 (95% CI, 1.20-9.13) and an adjusted odds
      ratio of 3.01 (95% CI, 1.06-8.58). CONCLUSION: HTLV-1 infection is associated
      with a first diagnosis of tuberculosis. This may have implications for
      tuberculosis control in places with high prevalence of HTLV-1.

PMID- 16284544
TI  - Deep Sylvian fissure chordoid meningioma: case report.
AB  - OBJECTIVE AND IMPORTANCE: A case of chordoid meningioma originating in the right
      sylvian fissure is reported. Chordoid meningiomas are uncommon tumors. This is
      the first reported case of a chordoid meningioma without dural attachment arising
      in the sylvian fissure. CLINICAL PRESENTATION: The patient presented with a
      generalized seizure. A heterogeneously enhancing right frontotemporal mass was
      identified on magnetic resonance imaging of the brain. INTERVENTION: The patient
      underwent a failed stereotactic biopsy attempt elsewhere. The tumor was
      ultimately resected using standard microsurgical techniques. CONCLUSION:
      Meningiomas originate from arachnoid cap cells and can arise at locations remote
      from the pachymeninges. Although rare, meningiomas should be included on the
      differential diagnosis of sylvian fissure lesions.

PMID- 16284543
TI  - Permanent neurological deficit related to magnetic resonance imaging in a patient
      with implanted deep brain stimulation electrodes for Parkinson's disease: case
      report.
AB  - OBJECTIVE AND IMPORTANCE: Deep brain stimulation (DBS) is an accepted treatment
      for patients with Parkinson's disease refractory to medication. The efficacy of
      this therapy has led to increasing numbers of patients receiving DBS implants.
      Importantly, physicians caring for patients with implantable neurostimulators
      must be aware of treatment guidelines for these patients, including the use of
      therapeutic ultrasound, diathermy, and imaging studies such as magnetic resonance
      imaging (MRI). CLINICAL PRESENTATION: We describe a case of serious, permanent
      neurological injury secondary to a radiofrequency lesion produced by heating of a
      DBS electrode associated with MRI of the lumbar spine in a patient with
      Parkinson's disease. INTERVENTION: MRI may be performed safely in patients with
      DBS devices only by following the specific guidelines of the manufacturer. The
      generalization of these conditions to other neurostimulation system positioning
      schemes, other scanners, and other imaging scenarios can lead to significant
      patient injuries. CONCLUSION: To prevent catastrophic incidents, the
      manufacturer's guidelines should be followed carefully because they are known to
      result in the safe performance of MRI examinations of patients with
      neurostimulation systems used for DBS.

PMID- 16284545
TI  - Neurocytoma of the VIIIth cranial nerve: case report.
AB  - OBJECTIVE AND IMPORTANCE: Neurocytomas are uncommon tumors of the CNS. To date,
      none have been described in association with a cranial nerve. We described the
      clinicopathological features of an example arising in the cochlear-vestibular
      portion of the VIIIth nerve with extension into the cerebellopontine angle.
      CLINICAL PRESENTATION: The patient, a 42-year-old female, presented approximately
      6 months ago with several episodes of worsening dizziness. On magnetic resonance
      imaging studies, a 2-cm enhancing lesion occupying the left internal auditory
      canal and protruding into the cerebellopontine angle cistern was detected with
      signal characteristics suggestive of vestibular neuroma. INTERVENTION: At
      surgery, the tumor was seen to originate from the cochlear-vestibular nerve
      bundle lying within the internal auditory canal, extended laterally to the level
      of the fundus and 4 mm medially into the cerebellopontine angle. No dural
      attachment was noted. With use of sharp dissection and bipolar cautery, portions
      of the tumor within the auditory canal were debulked. CONCLUSION: A unique
      example of a neurocytoma in association with a cranial nerve is documented.
      Possible explanations for the occurrence are explored. The topography of
      neurocytomas continues to expand.

PMID- 16284546
TI  - Pineal cyst apoplexy: case report and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Although most pineal cysts are clinically benign and
      asymptomatic, some can become symptomatic. Of the various symptomatic
      presentations, apoplexy is the rarest and most ill-defined. A comprehensive
      search of publications in the English language yielded 18 cases of pineal cyst
      apoplexy. We reviewed the literature to compare symptomatology and management
      strategies and their outcomes. CLINICAL PRESENTATION: A 29-year-old woman with a
      1-month history of headaches presented with an acute worsening of her symptoms
      with a severe occipital headache and trouble focusing when reading. Her
      neurological examination was otherwise normal. Magnetic resonance imaging showed
      pineal cyst apoplexy and accompanying hydrocephalus. INTERVENTION: A left
      paramedian craniotomy with a transcallosal, transchoroidal approach using an
      intraoperative neuronavigation system was used to resect a pineal cyst.
      Postoperative imaging showed complete removal of the cyst and resolution of the
      hydrocephalus. Follow-up imaging at 12 months demonstrated no evidence of
      recurrence or any hydrocephalus. The patient has remained asymptomatic for 18
      months. CONCLUSION: Pineal cyst apoplexy should always be considered when
      following a patient with a pineal cyst that becomes symptomatic. The most common
      symptom was severe headache of sudden onset or acute worsening. Other signs of
      hydrocephalus may or may not be present. Magnetic resonance imaging is essential
      to making a diagnosis. Although we believe that surgical resection is the most
      effective approach because it minimizes the risk for recurrence and complication,
      stereotactic aspiration has been used successfully to treat this condition.

PMID- 16284547
TI  - Spontaneous thoracic spinal cord herniation: three cases with long-term follow
      up.
AB  - OBJECTIVE AND IMPORTANCE: Spontaneous thoracic spinal cord herniation (STSCH) is
      an uncommon cause of thoracic myelopathy. Fewer than 40 cases have been reported
      in the English language literature with a mean follow-up of less than 6 months.
      CLINICAL PRESENTATION: We have encountered three patients diagnosed with STSCH in
      the last 6 years at our institution. These patients presented with symptoms and
      signs localizing to the thoracic spinal cord. Magnetic resonance imaging revealed
      ventral thoracic spinal cord displacement in each. INTERVENTION: One patient was
      treated surgically, two managed expectantly. Two patients have been followed for
      greater than 5 years, whereas a third has been followed for 15 months.
      CONCLUSION: Our experience suggests that patients with neurological symptoms and
      signs attributable to STSCH may not progress and therefore may be followed with
      clinical and magnetic resonance imaging surveillance. When surgery is indicated
      for progressive STSCH, late retethering may occur.

PMID- 16284548
TI  - Peduncular hallucinosis: insights from a neurosurgical point of view.
AB  - OBJECTIVE: Peduncular hallucinosis is a rare phenomenon characterized by visual
      hallucinosis and agitation. It appears mainly in vascular lesions affecting the
      brainstem, and some recent reports describe the preoperative and postoperative
      appearance of peduncular hallucinosis in patients affected through tumor
      compression at the brainstem. METHODS: Detailing the neurosurgical experiences
      with this syndrome, we review the available literature and provide
      pathoneurobiological insights to give the neurosurgeon an overall view of this
      phenomenon. RESULTS: Peduncular hallucinosis resolves spontaneously, and
      supportive medications might be helpful. Sacrifice of brainstem draining veins
      during surgery might contribute to the symptoms. CONCLUSION: The cranial base
      neurosurgeon should be aware not only of the phenomenon but the surgical
      influence in provoking it.

PMID- 16284551
TI  - Counteracting the effects of anticoagulants and antiplatelet agents during
      neurosurgical emergencies.
AB  - OBJECTIVE: Emergent neurosurgery may be precipitated or complicated by previous
      or concomitant administration of anticoagulants, thrombolytic medications, or
      antiplatelet agents. Recommendations are presented to reverse or counteract the
      effects of those drugs before or during neurosurgical interventions. METHODS:
      Directed literature review. RESULTS: Evidence-based data specific to neurosurgery
      are limited. CONCLUSION: Other clinical experience based on mechanisms of drug
      action within the coagulation process confirm that single or combined
      administration of platelet transfusions, fresh frozen plasma, cryoprecipitate,
      vitamin K, protamine, desmopressin, and recombinant activated factor VII can
      treat coagulopathies caused by warfarin, heparin, aspirin, adenosine diphosphate
      receptor antagonist, glycoprotein IIb/IIIa receptor blocking agents, and
      thrombolysis. Specific interventions and recommended dosages are reviewed.

PMID- 16284552
TI  - Human recombinant factor VII for emergency reversal of coagulopathy in
      neurosurgical patients: a retrospective comparative study.
AB  - OBJECTIVE: Severe coagulopathy in a neurosurgical patient with intracranial
      hemorrhage is a common and serious problem. Current therapy with vitamin K and
      fresh-frozen plasma (FFP) may be too slow in certain situations. There are
      reports of rapid reversal of coagulopathy using human recombinant factor VII. We
      present a retrospective controlled study of our experience with factor VII.
      METHODS: We used factor VII as a second-line therapy after initial attempts at
      reversal with FFP had failed. Factor VII was given to 29 patients in the
      neurosurgical intensive care unit; 24 patients treated before the introduction of
      factor VII were control subjects. The groups were matched by age, sex, cause of
      coagulopathy, and presence of intracranial hemorrhage. RESULTS: After initial FFP
      administration, the international normalized ratio (INR) changed from a mean of
      2.57 to 1.67 in the factor VII group and from 2.17 to 1.85 in control subjects.
      In all patients, INR tended to rebound. Before administration of factor VII, the
      mean INR was 2.206. After 1.4 mg of factor VII, mean INR decreased to 1.12 (P <
      0.05). Measured from admission, INR in the factor VII group normalized within
      6.78 +/- 2.68 hours, and in control subjects, within 47.44 +/- 9.88 hours (P <
      0.0005). Six factor VII patients and six control subjects died. The number of
      patients with good functional outcome (Glasgow Outcome Scale score of 5) was
      greater among patients treated with factor VII compared with those who received
      only vitamin K and FFP (nine versus two, P = 0.04). None of the deaths were the
      result of a thrombotic complication. There were no thrombotic complications in
      the factor VII group. CONCLUSION: Factor VII is safe and highly effective when
      emergency reversal of coagulopathy is desired and may improve the functional
      outcome. We speculate that the use of factor VII as first choice may result in
      decreased use of FFP and thus increase patient safety.

PMID- 16284553
TI  - Rapid administration of antifibrinolytics and strict blood pressure control for
      intracerebral hemorrhage.
AB  - OBJECTIVE: Hematoma growth is a major cause of poor outcome in patients with
      intracerebral hemorrhage. We evaluated the efficacy of a combination of rapid
      antifibrinolytic therapy and strict blood pressure control for prevention of
      hematoma growth in this retrospective study. METHODS: Systolic blood pressure was
      strictly controlled below 150 mm Hg by use of intravenously administered
      nicardipine (BPC). Prolonged infusion of antifibrinolytic therapy was given by
      intravenous administration of 1 g tranexamic acid over a period of 6 hours (PAF).
      Rapid administration of antifibrinolytic therapy was given by intravenous
      administration of 2 g tranexamic acid over a period of 10 minutes (RAF).
      Immediately after diagnosis of intracerebral hemorrhage on computed tomographic
      scan, 156 patients who were admitted within 24 hours of onset were treated with
      either a combination of PAF and BPC (PAF group) or a combination of RAF and BPC
      (RAF group). The incidence of hematoma growth determined by a second computed
      tomographic scan the day after admission was compared between the PAF and the RAF
      groups. RESULTS: Hematoma growth was observed in 11 (17.5%) of 63 patients in the
      PAF group and 4 (4.3%) of 93 patients in the RAF group using a 20% cutoff value
      for hematoma enlargement. The RAF group showed a significantly low incidence of
      hematoma growth compared with the PAF group (P < 0.05). Between the two groups,
      there was no significant difference in any of the other factors reported to
      affect hematoma growth. CONCLUSION: The combination of rapid administration of
      antifibrinolytics and strict blood pressure control may prevent hematoma growth
      in patients with intracerebral hemorrhage.

PMID- 16284555
TI  - Presentation, natural history, and management of carotid cavernous aneurysms.
AB  - OBJECTIVE: We present the largest reported cohort of carotid cavernous aneurysms
      (CCA), comparing the neuro-ophthalmic presentation, complications, and outcome
      with and without endovascular treatment. METHODS: Retrospective review of 185
      patients with 206 CCAs examined between 1980 and 2001 at a tertiary neuro
      ophthalmology and neurovascular service. Patients' symptoms and findings at
      presentation were recorded and compared with those at outcome. The effect of
      treatment on outcome and on complication rate was analyzed using the chi test,
      multivariate analysis of covariance, model-selection log-linear analysis, and
      multinomial logistic regression. RESULTS: Long-term follow-up was available for
      189 of 206 CCAs. Seventy-four CCAs underwent treatment (endovascular, 67 [91%];
      surgical treatment, 6 [9%]), and 115 were followed for an average of 4 years, two
      of which required later treatment. Treatment reduced the incidence and severity
      of pain, even after adjusting for the severity of initial pain (F(1,192 = 9.59, P
      = 0.002). Treatment did not significantly affect the patient's final diplopia
      after adjusting for their initial diplopia (F(1, 182 = 2.01, P = 0.158).
      Statistical examination revealed that the treated group had a higher proportion
      of neurological and visual complications than people who were not treated (2(2).
      = 25.26, P = 0.0003). CONCLUSION: Endovascular treatment of carotid cavernous
      aneurysms leads to a significantly higher rate of pain resolution compared with
      untreated patients, even after adjusting for initial pain severity. Diplopia may
      not resolve after treatment. The results of this study underscore our approach
      indicating treatment only in cases of debilitating pain, visual loss from
      compression, or diplopia in primary gaze or in patients with risk factors for
      major complications such as pre-existing coagulopathy or sphenoid sinus erosion.

PMID- 16284554
TI  - Safety of heparinization for cerebral aneurysm coiling soon after external
      ventriculostomy drain placement.
AB  - OBJECTIVE: Our practice has been to heparinize patients for cerebral aneurysm
      coiling even after recent external ventriculostomy drain (EVD) placement. The
      current medical literature cites a 12.5% symptomatic hemorrhage rate with
      heparinization after recent EVD placement. We reviewed our experience to
      determine our level of safety with this practice. METHODS: A search of our
      prospectively collected computerized aneurysm database revealed that from
      February 1998 to February 2004, 356 aneurysms were coiled, of which 119 patients
      had had recent EVD placement before coiling. During the same time period, 251
      subarachnoid hemorrhage patients underwent EVD placement without coiling or
      heparinization. We reviewed the head computed tomographic scan reports and
      medical records to determine the incidence of EVD-related hemorrhage in
      heparinized patients compared with nonheparinized patients. RESULTS: There was
      only 1 patient in the heparinized group who had a symptomatic EVD-related
      hemorrhage attributable to heparinization (0.8%) and 11 patients with
      asymptomatic EVD-related hemorrhage (9.2%). Among the nonheparinized patients,
      there were 3 patients who had symptomatic EVD-related hemorrhages (1.2%) and 22
      patients with asymptomatic EVD-related hemorrhages (8.8%) (P = not significant
      for both symptomatic and asymptomatic EVD-related hemorrhages). The time interval
      between EVD placement and heparinization in the heparinized patient with
      symptomatic EVD-related hemorrhage was 0.5 day; the mean time interval in the
      heparinized patients with asymptomatic EVD-related hemorrhage was 0.8 day; and in
      the heparinized patients with no hemorrhage, it was 0.8 day. The peak activated
      prothrombin time of the heparinized patient with symptomatic EVD-related
      hemorrhage was >150 seconds, the mean peak activated prothrombin time of the
      heparinized patients with asymptomatic EVD-related hemorrhage was 73.1 seconds,
      and that of the heparinized patients with no hemorrhage was 90.3 seconds.
      CONCLUSION: Heparinization for cerebral aneurysm coiling can be safely performed
      even after EVD placement within 24 hours, particularly if the activated
      prothrombin time is kept strictly controlled.

PMID- 16284556
TI  - Psychosocial effects of harboring an untreated unruptured intracranial aneurysm.
AB  - OBJECTIVE: The primary purpose of the study was to investigate the psychosocial
      effects of harboring a known but untreated unruptured intracranial aneurysm
      (UIA), information considered important to the decision of whether to treat or
      not treat an unruptured aneurysm. METHODS: Over a 24-month period, 70 Auckland
      Hospital patients with UIAs were identified. Of these, 30 completed treatment, 2
      patients died before treatment, and 38 were either not treated or treatment was
      unable to be completed during the time frame of the study. Of this group of 38
      untreated UIA patients, 23 were enrolled in the study and were assessed on a
      brief cognitive screen and a battery of psychosocial measures. Their performance
      was compared with a group of 26 treated UIA patients. RESULTS: Poorer functioning
      was reported by the untreated UIA group on most psychosocial measures when
      compared with the treated UIA group 6 months posttreatment, and 36% of untreated
      UIA patients presented with a pattern of significant psychosocial impairment when
      compared with the treated UIA group. Qualitative data from the current study
      suggested that a factor contributing to the poorer reported psychosocial
      functioning in the untreated group was past or current fear about their untreated
      UIA. CONCLUSION: A decrease in overall quality of life was found to be associated
      with harboring an identified but untreated UIA. Findings from the current study
      suggest that further investigation of psychosocial outcome in other groups of
      untreated UIA patients is warranted. Results also suggest that some untreated UIA
      patients might benefit from psychological intervention.

PMID- 16284557
TI  - Meningioma resection in the elderly: nationwide inpatient sample, 1998-2002.
AB  - OBJECTIVE: Morbidity and mortality rates reported for meningioma resection in the
      elderly vary widely. Thus, it is difficult for neurosurgeons to compare the risks
      and benefits of operating on elderly patients against opting for radiosurgery or
      watchful waiting. To address this issue, we studied the effect of advanced age on
      outcome after meningioma resection using the Nationwide Inpatient Sample.
      METHODS: We identified all patients over the age of 20 in the Nationwide
      Inpatient Sample database who underwent surgical resection of a meningioma
      between 1998 and 2002 and were admitted from home. Primary outcomes were in
      hospital mortality, adverse outcome (defined as death or discharge to a facility
      other than home), and length of hospitalization. Multivariate models were
      constructed to assess the effect of elderly age on the primary outcomes,
      adjusting for patient demographics, comorbid medical conditions, and hospital
      surgical volume. RESULTS: There were 8861 patients in the Nationwide Inpatient
      Sample database who underwent resection of meningioma during the study period;
      26.0% were age 70 or older. Each of the primary outcomes demonstrated a marked
      effect of advancing age. The in-hospital mortality rate was higher in the elderly
      than in the nonelderly (4.0% versus 1.1%, P < 0.001), as was the rate of
      discharge to a facility other than home (53.2% versus 16.6%, P < 0.001). Elderly
      patients also had a longer mean length of stay (7.2 versus 5.1 d P < 0.001).
      CONCLUSION: The association between elderly age and adverse outcome after
      meningioma resection suggests a note of caution before proceeding to surgery with
      these patients.

PMID- 16284558
TI  - Evaluation of fractionated radiotherapy and gamma knife radiosurgery in cavernous
      sinus meningiomas: treatment strategy.
AB  - OBJECTIVE: To investigate the respective role of fractionated radiotherapy (FR)
      and gamma knife stereotactic (GKS) radiosurgery in cavernous sinus meningioma
      (CSM) treatment. METHODS: The authors report the long-term follow-up of two
      populations of patients harboring CSMs treated either by FR (Group I, 38
      patients) or GKS radiosurgery (Group II, 36 patients). There were 31 females with
      a mean age of 53 years in Group I and 29 females with a mean age of 51.2 years in
      Group II. In 20 patients (Group I) and 13 patients (Group II), FR and GKS
      radiosurgery were performed as an adjuvant treatment. In 18 patients (Group I)
      and in 23 patients (Group II), FR and GKS radiosurgery were performed as first
      line treatment. In our early experience with GKS radiosurgery (1992, date of
      gamma knife availability in the department), patients with tumors greater than 3
      cm, showing close relationship with the optic apparatus (<3 mm) or skull base
      dural spreading, were treated by FR. Secondarily, with the advent of new devices
      and our growing experience, these criteria have evolved. RESULTS: The median
      follow-up period was 88.6 months (range, 42-168 mo) for Group I and 63.6 months
      (range, 48-92 mo) for Group II. According to Sekhar's classification, 26 (68.4%)
      patients were Grade III to IV in Group I and 10 (27.8%) patients in Group II (P <
      0.05); 23 (60.5%) patients had extensive lesions in Group I and 7 (19.4%)
      patients in Group II (P < 0.05). Mean tumor volume was 13.5 cm in Group I and 5.2
      cm in Group II (P < 0.05). Actuarial progression-free survival was 94.7% and
      94.4% in Group I and II, respectively. Clinically, improvement was seen for 24
      (63.2%) patients in Group I and for 21 (53.8%) patients in Group II (P > 0.05).
      Radiologically, 11 (29%, Group I) patients and 19 (Group II, 52.7%) patients
      showed tumor shrinkage (P = 0.04). Transient morbidity was 10.5% in Group I and
      2.8% in Group II. Permanent morbidity was 2.6% in Group I and 0% in Group II.
      CONCLUSION: FR and GKS radiosurgery are safe and efficient techniques in
      treatment of CSMs, affording comparable satisfactory long-term tumor control.
      However, GKS radiosurgery provides better radiological response, is far more
      convenient, and fits into most patients lives much better than FR. Therefore, in
      the authors' opinion, GKS radiosurgery should be advocated in first intention for
      patients with CSMs, whereas conventional radiotherapy should be reserved for
      cases that are not amenable to this technique, thus making these two therapeutic
      modalities not alternative but complementary tools in CS meningioma treatment
      strategy.

PMID- 16284559
TI  - Nausea and dizziness after vestibular schwannoma surgery: a multivariate analysis
      of preoperative symptoms.
AB  - OBJECTIVE: Nausea and dizziness are very discomforting for patients after
      vestibular schwannoma surgery and they impair recovery. METHODS: To identify
      preoperative symptoms and conditions that increase the risk of development of
      nausea after vestibular schwannoma surgery, a multivariate analysis was
      performed. One hundred fifteen patients with vestibular schwannoma had a
      microsurgical tumor removal in a standardized procedure in 2001 and 2002.
      Eighteen patients were excluded from the study because of previous surgery
      (recurrent tumors, 7 patients) or bilateral tumor occurrence (neurofibromatosis,
      11 patients). Analysis was performed regarding postoperative amount of antiemetic
      medication, vomiting, and subjective feeling of the patient. Tumor grading, body
      mass index, sex, previous complaints, examination at admission, and side of the
      tumor were taken in consideration. RESULTS: Women had significant longer
      postoperative complaints (mean, 3.0 d; standard error, 0.47) and needed longer
      antiemetic therapy (mean, 3.3 d; standard error, 0.49) than men (mean, 1.72 d;
      standard error, 0.21). Patients developing no significant postoperative
      complaints were all in the higher tumor grading group, Grades 3a, 4a, and 4b.
      There was a significant difference in the duration of antiemetic therapy between
      tumors graded 1 and tumors graded 3 or 4. Patients with a positive stepping test
      preoperatively had a tendency to demand less antiemetic medication. Women with
      small tumors are most likely to develop significant complaints after vestibular
      schwannoma surgery. CONCLUSION: It is possible to identify patients with a higher
      risk of postoperative nausea and dizziness after vestibular schwannoma surgery.
      This allows one to inform these patients preoperatively and to initiate an early
      postoperative drug therapy to ease their symptoms.

PMID- 16284560
TI  - Concussion in professional football: brain responses by finite element analysis:
      part 9.
AB  - OBJECTIVE: Brain responses from concussive impacts in National Football League
      football games were simulated by finite element analysis using a detailed
      anatomic model of the brain and head accelerations from laboratory
      reconstructions of game impacts. This study compares brain responses with
      physician determined signs and symptoms of concussion to investigate tissue-level
      injury mechanisms. METHODS: The Wayne State University Head Injury Model (Version
      2001) was used because it has fine anatomic detail of the cranium and brain with
      more than 300,000 elements. It has 15 different material properties for brain and
      surrounding tissues. The model includes viscoelastic gray and white brain matter,
      membranes, ventricles, cranium and facial bones, soft tissues, and slip interface
      conditions between the brain and dura. The cranium of the finite element model
      was loaded by translational and rotational accelerations measured in Hybrid III
      dummies from 28 laboratory reconstructions of NFL impacts involving 22
      concussions. Brain responses were determined using a nonlinear, finite element
      code to simulate the large deformation response of white and gray matter. Strain
      responses occurring early (during impact) and mid-late (after impact) were
      compared with the signs and symptoms of concussion. RESULTS: Strain concentration
      "hot spots" migrate through the brain with time. In 9 of 22 concussions, the
      early strain "hot spots" occur in the temporal lobe adjacent to the impact and
      migrate to the far temporal lobe after head acceleration. In all cases, the
      largest strains occur later in the fornix, midbrain, and corpus callosum. They
      significantly correlated with removal from play, cognitive and memory problems,
      and loss of consciousness. Dizziness correlated with early strain in the orbital
      frontal cortex and temporal lobe. The strain migration helps explain coup
      contrecoup injuries. CONCLUSION: Finite element modeling showed the largest brain
      deformations occurred after the primary head acceleration. Midbrain strain
      correlated with memory and cognitive problems and removal from play after
      concussion. Concussion injuries happen during the rapid displacement and rotation
      of the cranium, after peak head acceleration and momentum transfer in helmet
      impacts.

PMID- 16284561
TI  - Intracranial pressure response to induced hypertension: role of dynamic pressure
      autoregulation.
AB  - OBJECTIVE: Induced hypertension is commonly used to improve cerebral perfusion,
      but this treatment may have the deleterious side effect of raising intracranial
      pressure (ICP). We tested the hypothesis that dynamic pressure autoregulation
      testing could identify patients who might develop increased ICP during induced
      hypertension. METHODS: Twenty-two studies were performed in 21 patients. Baseline
      dynamic testing of autoregulation by cuff deflation and carotid compression
      techniques was performed. After phenylephrine was infused to increase mean
      arterial pressure by 20 to 30 mm Hg, cuff deflation tests were repeated. RESULTS:
      The average increase in mean arterial pressure was 32.2 +/- 16.1 mm Hg. This
      increase was accompanied by increased flow velocity (P < 0.001), brain tissue PO2
      (P = 0.011), and regional cerebral blood flow (P = 0.008). Also, dynamic pressure
      autoregulation consistently improved (P = 0.015). Induced hypertension caused
      increased ICP (iICP) in 12 patients and a decrease in ICP (dICP) in 9. Baseline
      jugular venous oxygen saturation in the iICP group was 82 +/- 10% compared with
      70 +/- 10% in dICP patients (P = 0.02). Baseline dynamic autoregulatory index for
      the cuff deflation tests (1.8 +/- 1.4) and baseline transient hyperemic response
      ratio for the carotid compression tests (1.11 +/- 0.07) were significantly lower
      in iICP patients (dICP group: autoregulatory index 3.2 +/- 1.7, P = 0.06;
      transient hyperemic response ratio 1.26 +/- 0.11, P = 0.009). Flow velocity
      increased more with the increase in blood pressure in the iICP group than in the
      dICP group: 19.0 +/- 6.8 cm/s versus 10.2 +/- 6.3 cm/s (P = 0.007). CONCLUSION:
      The patients who had an increase in ICP with induced hypertension had a greater
      degree of impairment of autoregulation and induced hypertension resulted in a
      greater increase in flow velocity.

PMID- 16284562
TI  - Intracranial epidural hematoma in newborn infants: clinical study of 15 cases.
AB  - OBJECTIVE: Epidural hematoma (EDH) in newborn infants is rare. We have described
      the history of 15 newborns with EDH to provide a better understanding of this
      pathology. METHODS: This is a descriptive case series study using a retrospective
      review of the medical records of newborns who were admitted to the Pediatric
      Intensive Care Unit and Neurosurgery Department with the diagnosis of birth EDH
      over a 24-year period (1979-2002). RESULTS: There was no sex predominance, and
      most of the mothers were young, nulliparous women. The time latency from birth to
      the first signs varied from 0 to 24 hours. Clinical presentation was nonspecific:
      seizures and hypotonia were the main symptoms. The parietal area was the most
      frequent location. Surgical drainage was required in nine patients, and no deaths
      were reported. CONCLUSION: This report highlights the clinicoradiological
      characteristics of newborn EDH, which occurs more frequently in newborns that
      experienced difficult delivery from a nulliparous mother. Surgery is not a rule;
      some patients can be managed with conservative treatment. The outcome is
      generally good.

PMID- 16284563
TI  - Detection of root avulsion in the dominant C7 obstetric brachial plexus lesion:
      experience with three-dimensional constructive interference in steady-state
      magnetic resonance imaging and electrophysiology.
AB  - OBJECTIVE: Preoperative, reliable detection by ancillary investigations of spinal
      nerve root avulsions in infants with severe obstetric brachial plexus lesions to
      avoid ineffective operative repair from deceivingly intact but actually avulsed
      nerve roots. METHODS: Ten infants were selected with an infrequent, severe
      dominant C7 lesion, primarily because of the anatomically distinct
      supraclavicular course of this spinal nerve. Three-dimensional constructive
      interference in steady-state magnetic resonance imaging (3D CISS MRI) studies
      under mild sedation were performed and evaluated for detection of avulsed nerve
      roots by two experienced neuroradiologists. Preoperative electrodiagnostics
      (electromyography and somatosensory evoked potentials) as well as intraoperative
      somatosensory potentials and muscle contractions after electrostimulation were
      recorded. Preoperative and intraoperative ancillary investigations were
      correlated with intraoperative findings in eight patients and clinical status in
      two children who recovered spontaneously. RESULTS: Despite two minor motion
      artifacts, the quality of the 3D CISS MRI studies was good. In 8 of 10 patients,
      prediction of root continuity was consistent with operative or clinical findings,
      and 2 remained doubtful. Preoperative and intraoperative electrodiagnostics
      tended not to correlate with intraoperative findings in this small, selected
      group. CONCLUSION: 3D CISS MRI provides good images of anterior and posterior
      spinal roots in infants with obstetric brachial plexus lesions. Images seem to
      allow accurate prediction of root avulsion in the majority of patients. In this
      study, electrodiagnostics were of limited value.

PMID- 16284564
TI  - Atlantoaxial rotatory fixation: part 2--new diagnostic paradigm and a new
      classification based on motion analysis using computed tomographic imaging.
AB  - OBJECTIVE: This is Part II of a study on atlantoaxial rotatory fixation (AARF)
      that aims to introduce a new diagnostic paradigm and a new classification of this
      condition based on motion analysis of C1C2 rotation using computed tomographic
      (CT) imaging. This phase of the study is possible because Part I succeeded in
      defining physiological C1C2 axial rotation with CT data from 21 normal children,
      displayed in a highly concordant composite motion curve, which is used as the
      normal template for the present study. AARF is defined as flagrant departure from
      normal motion dynamics as delineated by abnormal motion curves. The new
      classification is predicated on the graded amount of pathological stickiness in
      the restricted rotation. METHODS: Forty children age 1.5 to 14 years with painful
      "cock-robin" necks resulting from minor trauma or otolaryngological procedures
      were subjected to 3 CT examinations: 1) in the presenting (P) position; 2) with
      the nose pointing up (P0 position); and 3) with the head forcefully turned to the
      opposite side as much as the patient could tolerate (P_ position). The angles
      made by C1 and C2 and the separation angle C1C2 degrees (C1 minus C2 degrees)
      were obtained as described in Part I. The test motion curve was generated by
      plotting C1 against C1C2 angles, and all motion curves were analyzed in the
      context of the normal template. RESULTS: Five distinct groups with highly
      characteristic motion curves could be identified. Group 1 (n = 5) patients showed
      essentially unaltered ("locked") C1C2 coupled configurations regardless of
      corrective counterrotation, with curves that are horizontal lines in the upper
      two quadrants of the template. Group 2 (n = 7) patients had reduction of the C1C2
      separation angle with forced correction, but C1 could not be made to cross C2.
      Their curves slope downward from right to left in the upper quadrants but never
      traverse the x axis. Group 3 (n = 9) patients showed C1C2 crossover, but only
      when the head was cranked far to the opposite side. Their motion curves traverse
      the x axis left of C1 = -20 degrees. Groups 1, 2, and 3 motion dynamics are
      respectively classified as Types I, II, and III AARF in descending degree of
      pathological stickiness, which is in essence a resistance against closure of the
      C1C2 angle to counterrotation. Group 4 (n = 14) patients had normal dynamics, and
      Group 5 (n = 5) patients showed motion curve features between normal and Type III
      AARF, designated as belonging to the diagnostic gray zone, an uncertain group
      that may or may not revert to normal dynamics with only comfort measures.
      CONCLUSION: AARF can be reliably diagnosed with a simple and practical CT
      protocol and construction of a three-point motion curve superimposed on a
      reusable normal template. The type of AARF, reflective of the severity of
      pathological stickiness of rotation, can be identified readily by the shape of
      the motion curve. This system of classification is useful in selecting the best
      regimen of management.

PMID- 16284565
TI  - Atlantoaxial rotatory fixation: part 3-a prospective study of the clinical
      manifestation, diagnosis, management, and outcome of children with alantoaxial
      rotatory fixation.
AB  - OBJECTIVE: This is a prospective study of the clinical manifestations, diagnostic
      motion analysis, management, and outcome of children with atlantoaxial rotatory
      fixation (AARF). METHODS: Fifty children presenting with painful torticollis were
      subjected to the three-head positions diagnostic computed tomographic scanning
      protocol described in Part II of our AARF study. Twenty-nine children qualified
      as having AARF (8 Type I, 11 Type II, and 10 Type III), and six children were
      classified in the diagnostic gray zone (DGZ). The AARF patients were given either
      halter or calipers traction depending on the type and chronicity of pretreatment
      delay. Upon reduction, patients were immobilized with either a cervicothoracic
      brace or a halo. Recurrence of AARF on halo and patients whose deformity was not
      reducible were given posterior C1C2 fusion at the best achievable alignment. The
      difficulty and results of treatment were measured according to the following:
      duration of traction, number of reduction slippage, percent not reducible by
      traction, percent needing halo, percent needing fusion, total duration of
      treatment, total number of treatment procedures, and percent who lost normal C1C2
      dynamics. Results were compared between groups stratified by AARF types, by
      chronicity of pretreatment delay (acute << 1 mo, subacute = 1-3 mo, chronic > or
      = 3 mo) and by the presence or absence of recurrence (recurrent AARF defined as
      having two or more slippages). DGZ patients were treated with only comfort
      measures for 2 weeks and then restudied. Only those children with persistent
      symptoms and DGZ or worse motion dynamics were given traction and bracing.
      RESULTS: Neither age nor etiology significantly influenced the severity of AARF.
      There was only a slight tendency for children younger than 5 years, and for
      trauma, to associate with severe C1C2 interlock. Delay of treatment up to 11
      months did not result in improvement of the neck restriction or in abatement of
      pain. In fact, there are strong suggestions that prolonged delay could lead to
      worsening of the rotatory dynamics: Type I AARF are highly correlated with delays
      longer than 3 months and Type III with delays less than 1 month. Also, four
      patients who had serial motion studies during the delay period showed clear
      worsening in the pathological stickiness in C1C2 rotation. In addition, chronic
      rotatory deformity led to progressive occiput -C1 separation or laxity
      teleologically to compensate for a skewed visual axis. The mean occiput -C1
      separation angle for chronic patients was 31.2 degrees versus 5 degrees for acute
      patients and less than 3 degrees for normal children. The difficulty and duration
      of treatment, the number of reslippage after reduction, the rate of
      irreducibility, the need for halo and fusion, and the percentile of patients
      ultimately loosing normal C1C2 rotation were significantly greater with Type I
      patients than Type III patients, with Type II patients being intermediate.
      Likewise, chronic patients of all AARF types were much worse in all parameters
      than acute patients; subacute patients were closer to chronic patients in
      complexity and outcome. Severity and chronicity exerted independent effects on
      outcome, and the worse identifiable subgroup were the chronic Type I patients
      versus the best subgroup of acute Type III patients.Thirteen patients developed
      recurrent AARF; they had much worse prognosis in all aspects measured than
      nonrecurrent patients. Recurrence was adversely influenced by both the severity
      (type) and chronicity of AARF. Half of the DGZ patients resolved with analgesics,
      but two of six remained symptomatic and in DGZ dynamics, and one deteriorated to
      Type III AARF. Two of those three patients responded easily to traction and
      bracing, and one was lost to follow-up. CONCLUSION: Children with painful
      torticollis should be subjected to the three-position computed tomographic
      diagnostic protocol, not only to secure the diagnosis of AARF but also to grade
      the severity of the condition by virtue of the dynamic motion curve. Closed
      reduction with traction should be instituted immediately to avoid the serious
      consequences of chronic AARF. Proper typing and reckoning of the pretreatment
      delay are requisites for selecting treatment modalities. Recurrent dislocation
      and incomplete reduction should be treated with posterior C1C2 fusion in the best
      achievable alignment. Open reduction and halo immobilization to avoid permanent
      fixation can be tried with select cases.

PMID- 16284566
TI  - Spinal cord intradural arteriovenous fistulae: anatomic, clinical, and
      therapeutic considerations in a series of 32 consecutive patients seen between
      1981 and 2000 with emphasis on endovascular therapy.
AB  - OBJECTIVE: To review our series of intradural spinal cord arteriovenous fistulas
      (SCAVFs), analyzing symptoms and related angioarchitecture, and to study the
      morphological and clinical results of embolization. METHODS: Thirty-two SCAVFs
      (in 22 adults and 10 children) were treated between 1981 and 2000. These lesions
      were classified as microarteriovenous fistulas (mAVFs) or macroarteriovenous
      fistulas (MAVFs) according to shunt morphology. Location, architecture,
      presenting symptoms, and age group were detailed. The selection of patients for
      endovascular versus surgical treatments was analyzed, as were the anatomic and
      clinical results obtained by embolization with n-butylcyanoacrylate. Clinical
      status was evaluated according to the Karnofsky Performance Scale score. RESULTS:
      Ten SCAVFs were found in the pediatric population (four mAVFs and six MAVFs). All
      four mAVFs presented with acute symptoms. Three mAVFs (two cervical and one
      thoracic) presented hematomyelia; in one patient with a thoracic AVF,
      subarachnoid hemorrhage was suspected. All six MAVFs were located in the
      thoracolumbar cord (five associated with hereditary hemorrhagic telangiectasias).
      Four of the six MAVFs presented with hemorrhage. In the adult population, there
      were 21 mAVFS (95%) and one MAVF (5%). Only two mAVFs were found in the cervical
      cord, all other shunts affecting the thoracolumbar region. Hemorrhage was present
      in 6 of the 22 cases seen in adults (27%). The symptoms of SCAVFs did not differ
      from those found in spinal cord arteriovenous shunts of nidus type. Pial venous
      reflux and congestion were the most frequently encountered features in both the
      adult and pediatric groups. Arterial aneurysms (different from false aneurysms)
      were not found in association with hemorrhagic presentation of SCAVFs. Mean
      follow-up in our series was 3.3 years. Of the MAVFs, 86% were embolized, with 67%
      cured. The others had more than 75% occlusion. All patients followed up improved
      significantly. Of the mAVFs, 48% were treated endovascularly. Successful
      embolization was performed in 75% of patients. One patient was not embolized
      because of vasospasm, whereas 67% percent of mAVFs were completely occluded, 22%
      were more than 90% occluded, and 11% were 75% occluded. Complementary surgery was
      deemed unnecessary. All patients with mAVFs improved significantly at follow-up.
      Transient complications occurred in 22% of all patients, with no permanent
      morbidity or mortality. No patient bled or rebled after embolization. Thirty-six
      percent of mAVFs were operated on because of anticipated technical difficulties
      for endovascular approach or distal localization of the shunt. CONCLUSION:
      Endovascular treatment of SCAVFs stabilizes, normalizes, or improves neurological
      symptoms in all patients at long-term follow-up, with no bleeds or rebleeds.
      Embolization of SCAVFs with glue is a safe treatment that compares favorably with
      other approaches and significantly improves the poor natural history of the
      disease.

PMID- 16284567
TI  - Incidence and characteristics of spinal decompression surgery after the onset of
      symptoms of amyotrophic lateral sclerosis.
AB  - OBJECTIVE: The high incidence of spondylosis in patients at the mean age of onset
      (55.7 yr) of amyotrophic lateral sclerosis (ALS) can make recognition of ALS as a
      cause of weakness difficult. METHODS: To assess the impact of this diagnostic
      dilemma on neurosurgical practice, we performed a retrospective analysis of a
      database of more than 1500 patients with motor neuron disease. RESULTS: Of 1131
      patients with typical, sporadic ALS, 47 (4.2%) underwent decompressive spinal
      surgery after the onset of retrospectively recognized symptoms of ALS. Among 55
      operations in 47 ALS patients, 86% yielded no improvement, 9% produced minor
      improvement, and only 5% provided significant benefit. Cervical decompression was
      performed in 56%, lumbar in 42%, and thoracic in 2%. Foot drop was a symptom
      prompting surgery in 11 patients, and in 10, this finding was subsequently
      attributed solely to ALS. No differences between ALS patients who underwent
      spinal decompression and other ALS patients were noted regarding age at symptom
      onset, severity of impairment at time of diagnosis, or rate of disease
      progression. Not surprisingly, patients who had spinal surgery tended to have a
      longer interval between retrospectively recognized symptom onset and diagnosis of
      ALS. CONCLUSION: A small but significant number of patients with unrecognized ALS
      undergo spinal surgery that in retrospect may be inappropriate. The possibility
      of ALS must be considered in the evaluation of patients with weakness even in the
      presence of radiographic evidence of spondylosis and nerve root or spinal cord
      impingement.

PMID- 16284568
TI  - Spinal cord stimulation electrode design: a prospective, randomized, controlled
      trial comparing percutaneous with laminectomy electrodes: part II-clinical
      outcomes.
AB  - OBJECTIVE: Spinal cord stimulation, in use for more than 30 years, has evolved
      into an easily implemented technique involving percutaneous or laminectomy
      electrode placement. In a randomized comparison of four-contact percutaneous and
      four-contact insulated laminectomy electrodes placed at the same level in the
      dorsal, epidural midline, quantitative measures of stimulator performance
      revealed significant technical advantages for the laminectomy electrodes. Our
      prospective, randomized, controlled trial compares clinical results in these same
      patients. METHODS: Impartial third parties followed our series of 24 patients
      with failed back surgery syndrome to gather clinical outcome data. We defined
      "success" as at least 50% sustained relief of pain and patient satisfaction with
      the result of treatment. RESULTS: At a mean follow-up of 1.9 years, 10 of 12
      patients receiving the laminectomy electrode and 5 of 12 patients receiving the
      percutaneous electrode reported a successful outcome (P < 0.05). Follow-up at a
      mean of 2.9 years showed that this result was maintained in 5 of 12 patients with
      the laminectomy electrode and 3 of 12 with the percutaneous electrode (not
      statistically significant). Many patients reported improvements in most
      activities of daily living, and loss of function was rare. In addition, 9
      patients with laminectomy electrodes and 4 with percutaneous electrodes reducted
      or eliminated analgesic intake (P < 0.05), and 2 returned to work. No electrode
      migration was observed. CONCLUSION: Laminectomy electrode placement, although
      more invasive than percutaneous placement, yields significantly better clinical
      results in patients with failed back surgery syndrome at mean 1.9 years follow
      up. In our small sample, however, the statistical significance of this advantage
      disappeared at mean 2.9 years follow-up.

PMID- 16284569
TI  - Expression of structural proteins and angiogenic factors in normal arterial and
      unruptured and ruptured aneurysm walls.
AB  - OBJECTIVE: To identify differences in the expression of certain structural
      proteins and angiogenic growth factors in vessel tissues that represent different
      phases of the process of intracranial aneurysm formation and rupture: normal
      vessel wall, intact (unruptured) aneurysm wall, and ruptured vessel wall.
      METHODS: The novel study design involved 10 pairs of specimens (ruptured and
      unruptured aneurysm wall) obtained perioperatively during clipping operations in
      10 patients with multiple aneurysms. All surgeries were performed within 5 days
      of subarachnoid hemorrhage. As controls, five circle of Willis specimens were
      obtained from five cadavers. Sections of each of the 25 specimens were separately
      immunostained for five structural proteins (collagen Types III and IV, alpha
      smooth muscle actin, fibronectin, and laminin) and three angiogenic factors
      (vascular endothelial growth factor, basic fibroblast growth factor, and
      transforming growth factor-alpha). Levels of expression for each protein and
      factor were graded, and the average grades for each tissue group were recorded
      and compared. RESULTS: Among the structural proteins studied, fibronectin
      specifically is densely expressed in ruptured aneurysms, which is graded as 2.0.
      However, its expression is less prominent both in nonaneurysmal vessel wall
      (Grade 1.0) and unruptured aneurysm vessel wall (Grade 1.1). Contrary to
      fibronectin, laminin is more intensely and regularly expressed in normal vessel
      wall (Grade 2.7) than in ruptured (Grade 1.1) and unruptured (Grade 1.0)
      aneurysmal specimens. Among the angiogenic growth factors studied, transforming
      growth factor-alpha shows a peculiar grading of staining, different from the
      other two angiogenic factors examined, so that it is more highly expressed in
      normal circle of Willis specimens (Grade 2.1) than in unruptured and ruptured
      aneurysm walls, graded as 0.5 and 0.6, respectively. CONCLUSION: Normal vessel
      wall, unruptured aneurysm wall, and ruptured aneurysm wall exhibit different
      levels and patterns of expression for the structural proteins and regulator
      growth factors investigated. If one accepts the premise that immunohistochemical
      study has its inherent methodological problems, these results suggest that the
      biological mediators of aneurysm formation in a vessel wall differ from those of
      the biological mediators of aneurysm rupture. There was a novel finding related
      to fibronectin and laminin: the results indicated that a rise in the fibronectin
      to-laminin ratio in an unruptured aneurysm wall may contribute to rupture. A drop
      in transforming growth factor-alpha expression in a vessel wall may also
      contribute to aneurysm formation.

PMID- 16284570
TI  - Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous
      malformation 3.
AB  - OBJECTIVE: To identify the CCM3 gene in a population of 61 families with a
      positive family history of cerebral cavernous malformations (CCM), 8 of which had
      suggestive linkage to the CCM3 locus. METHODS: We searched for mutations within
      the CCM3 interval using a high-throughput screening technique, temperature
      gradient capillary electrophoresis. Mutations detected by this device were
      subsequently sequenced, and the results were analyzed. RESULTS: A recent study by
      Bergametti et al. established Programmed Cell Death 10 (PDCD10) as the gene
      responsible for CCM3. We hereby confirm PDCD10 as the CCM3 gene by reporting four
      novel mutations in 61 CCM families. Two of these mutations were identical and
      produced a stop codon in exon 7. Another two resulted in frameshift mutations in
      exon 6, although the mutations occurred at different points along the exon. The
      last mutation caused a frameshift in exon 9. Of note, mutations in these families
      completely cosegregated with the trait. Three of the five families had prior
      linkage data suggestive of the CCM3 locus, whereas the remaining two were
      identified in index patients with a positive family history but no linkage data.
      CONCLUSION: Our data establish PDCD10 as the gene responsible for CCM in families
      linking to the CCM3 locus. The discovery of the third gene involved in inherited
      forms of CCM, after KRIT1 and Malcavernin, is an important step toward dissecting
      the molecular pathophysiology of this disease.

PMID- 16284571
TI  - Homologous transplantation of neural stem cells to the injured spinal cord of
      mice.
AB  - OBJECTIVE: Murine neural stem cells (NSCs) were homografted onto the injured
      spinal cord (SC) to assess their potential to improve motor behavior, to
      differentiate as neurons, and to establish synapse-like contacts with the
      descending axonal paths of the host. In addition, we investigated whether
      transduced NSCs over-expressing vascular endothelial growth factor might exert
      any angiogenetic effect in the injured SC. METHODS: NSCs derived from mouse
      embryos were transduced to express either green fluorescent protein or vascular
      endothelial growth factor. The cells were engrafted in mice where an extended
      dorsal funiculotomy had been performed at the T8-T9 level. At intervals from 4 to
      12 weeks after grafting, motor behavior was assessed using an open field
      locomotor scale and footprint analysis. At the same time points, the SC was
      studied by conventional histology, immunohistochemistry, and fluorescence
      microscopy. The interactions between the grafted NSCs and descending axonal paths
      were investigated using anterogradely transported fluorescent axonal tracers.
      RESULTS: By the 12-week time point, mice engrafted with NSCs significantly
      improved both their locomotor score on open field test and their base of support
      on footprint analysis. Histological studies showed that green fluorescent protein
      positive NSCs survived as long as 12 weeks after grafting, migrated from the
      grafting site with a tropism toward the lesion, and either remained
      undifferentiated or differentiated into the astrocytic phenotype without neuronal
      or oligodendrocytic differentiation. Interestingly, the NSC-derived astrocytes
      expressed vimentin, suggesting that these cells differentiated as immature
      astrocytes. The tips of severed descending axonal paths came adjacent to grafted
      NSCs without forming synapse-like structures. When genetically engineered to over
      express vascular endothelial growth factor, the grafted NSCs significantly
      increased vessel density in the injured area. CONCLUSION: In the traumatically
      injured mice SC, NSC grafting improves motor recovery. Although differentiation
      of engrafted NSCs is restricted exclusively toward the astrocytic phenotype, the
      NSC-derived astrocytes show features that are typical of the early phase after SC
      injury when the glial scar is still permissive to regenerating axons. The
      immature phenotype of the NSC-derived astrocytes suggests that these cells might
      support neurite outgrowth by the host neurons. Thus, modifying the glial scar
      with NSCs might enhance axonal regeneration in the injured area. The use of
      genetically engineered NSCs that express trophic factors appears to be an
      attractive tool in SC transplantation research.

PMID- 16284572
TI  - Human marrow stromal cell treatment provides long-lasting benefit after traumatic
      brain injury in rats.
AB  - OBJECTIVE: This study was designed to investigate the effects of human bone
      marrow stromal cell (hMSC) administration in rats for 3 months after traumatic
      brain injury (TBI). METHODS: Adult male Wistar rats (n = 60) were injured with
      controlled cortical impact and divided into four groups. The three treatment
      groups (n = 10 each) were injected with 2 x 10, 4 x 10, and 8 x 10 hMSCs,
      respectively, intravenously, whereas the control group (n = 30) received
      phosphate-buffered saline. All injections were performed 1 day after injury into
      the tail veins of rats. Neurological functional evaluation of animals was
      performed before and after injury by use of Neurological Severity Scores. Animals
      were sacrificed 3 months after TBI, and brain sections were stained by
      immunohistochemistry. RESULTS: Statistically significant improvement in
      functional outcome was observed in all three treatment groups compared with
      control values (P < 0.05). This benefit was visible 14 days after TBI and
      persisted until 3 months (end of trial). There was no difference in functional
      outcome among the three treatment groups. Histological analysis showed that hMSCs
      were present in the lesion boundary zone at 3 months with all three doses tested.
      CONCLUSION: hMSCs injected in rats after TBI survive until 3 months and provide
      long-lasting functional benefit. Functional improvement may be attributed to
      stimulation of endogenous neurorestorative functions such as neurogenesis and
      synaptogenesis.

PMID- 16284574
TI  - Bromophenol blue staining of tumors in a rat glioma model.
AB  - OBJECTIVE: For patients with gliomas, decreasing the tumor burden with
      macroscopic surgical resection may affect quality of life, time to tumor
      progression, and survival. Injection of bromophenol blue (BPB) may enhance
      intraoperative visualization of an infiltrating tumor and its margins and improve
      the extent of resection. In this study, we investigated the uptake of BPB in
      experimental rat brain tumors. METHODS: We first conducted a toxicity study with
      bolus intravenous injections of 5, 60, and 360 mg/kg doses of BPB in nontumor
      bearing Fischer 344 rats. No adverse effects were observed in any of the animals
      during the 60 day observation period. We then injected 9L tumor cells
      intracerebrally into Fischer 344 rats and approximately 2 weeks later,
      administered a bolus intravenous injection of 5 to 360 mg/kg BPB. Fifteen minutes
      after BPB injection, we sacrificed the animals and removed their brains. In a
      subsequent study, we injected 180 mg/kg BPB and sacrificed animals at several
      time points to monitor tumor staining over time. RESULTS: The stain was clearly
      visible and localized to the tumor for all BPB concentrations 60 mg/kg or
      greater, and in an additional experiment, we found that tumor staining persisted
      for at least 8 hours after BPB injection. CONCLUSION: We conclude that BPB helped
      visualize experimental tumors at time points from a few minutes to several hours
      after injection. Because BPB also proved to be nontoxic to the animals at
      effective concentrations, we believe the compound may be potentially useful in
      helping neurosurgeons visualize brain tumors in humans.

PMID- 16284573
TI  - Local delivery of a synthetic endostatin fragment for the treatment of
      experimental gliomas.
AB  - OBJECTIVE: Endostatin is an anti-angiogenic agent that blocks matrix
      metalloproteinase-2 and inhibits endothelial cell proliferation. Currently,
      endostatin is available through recombinant technology, which limits its broader
      use. In this study, a synthetic endostatin fragment (EF) was analyzed to
      determine its anti-angiogenic properties when locally delivered by controlled
      release polymers and to establish its effect as a treatment for experimental
      gliomas. METHODS: Cytotoxicity of EF against 9L gliosarcoma and F98 glioma was
      determined in vitro. EF was loaded into polyanhydride-poly-(bis-[carboxyphenoxy
      propane]-sebacic-acid) (pCPP:SA) polymers at increasing concentrations.
      Pharmacokinetics of the EF/polymer formulations were defined in vitro. Anti
      angiogenic properties of the EF/polymer formulations were evaluated in the rat
      cornea micropocket assay. Toxicity and efficacy of locally delivered EF polymers
      either alone or combined with systemic bischloroethylnitrosourea (carmustine)
      were determined in rats intracranially challenged with 9L gliosarcoma. RESULTS:
      EF showed scarce cytotoxicity against 9L and F98 in vitro. EF/pCPP:SA
      formulations showed sustained release by day 19. Mean corneal angiogenesis index
      20 days after tumor implantation was 4.5 +/- 0.7 for corneas implanted with 40%
      EF/pCPP:SA compared with controls (8.5 +/- 1.3, P = 0.02). Intracranial efficacy
      studies showed that EF polymers alone did not prolong animal survival.
      Combination of 40% EF/pCPP:SA polymers with systemic bischloroethylnitrosourea
      (carmustine) prolonged survival (median survival of 44 d, P = 0.001) and
      generated 33% long-term survivors. CONCLUSION: Controlled-release polymers can
      effectively deliver a biologically active EF in a sustained fashion. EF inhibits
      angiogenesis in vitro and in vivo, and even though EF does not prolong survival
      as a single agent, it exhibits a synergistic effect when combined with systemic
      bischloroethylnitrosourea (carmustine) in the intracranial 9L gliosarcoma model.

PMID- 16284576
TI  - Is magnetic resonance imaging safe for patients with neurostimulation systems
      used for deep brain stimulation?

PMID- 16284575
TI  - Anticoagulation regimes and their influence on the occlusion rate of aneurysms:
      an experimental study in rabbits.
AB  - OBJECTIVE: Our purpose was to determine whether anticoagulation has an influence
      on the occlusion rate and thromboembolic occurrence in saccular aneurysms treated
      with Guglielmi detachable coils. METHODS: Aneurysms in the right CCA were created
      in rabbits. Group 1 served as a control group (n = 6) without embolization or
      anticoagulation. In Groups 2 to 5, aneurysms were embolized. In Group 2, no
      anticoagulation was given (n = 5). Group 3 received heparin before the placement
      of the first coil, then low molecular weight heparin (LMWH) for the next 2 days
      (n = 7). In Group 4, additional aspirin was administered after 2 days until
      sacrifice (n = 10). Group 5 received heparin before the placement of the first
      coil, then a LMHW was administered daily until sacrifice (n = 5). Angiography was
      performed 3 months after coiling, followed by a histological examination.
      RESULTS: Histopathological evaluation showed thrombus formation with
      neovascularization, regardless of the anticoagulation regime used. Only in the
      group with LMWH over 3 months was the thrombus not focally, properly organized,
      especially in the dome. The coils in the neck showed, however, the same fibrous
      scar tissue as in the other groups. CONCLUSION: Anticoagulation with heparin
      during the first days, followed by aspirin, appears unlikely to affect the
      occlusion rate in aneurysms. LMWH over a long period, however, could impair
      thrombus organization. Therefore, in regard to thrombus organization, an
      anticoagulation regime with aspirin seems to be superior to LMWH. This could play
      an important role in the prevention of thromboembolic events in humans treated
      with Guglielmi detachable coils.

PMID- 16284577
TI  - In vitro stabilizing effect of a transforaminal compared with two posterior
      lumbar interbody fusion cages.
AB  - STUDY DESIGN: An in vitro biomechanical flexibility test on different lumbar
      interbody fusion cages using monosegmental lumbar spine specimens. OBJECTIVE: To
      investigate the stabilizing effect of a transforaminal lumbar interbody fusion
      (TLIF) cage compared with two established posterior lumbar interbody fusion
      (PLIF) cages. SUMMARY OF BACKGROUND DATA: TLIF using interbody fusion cages is
      gaining more and more popularity in the treatment of degenerative disc disease.
      However, only little is known on its biomechanical behavior. METHODS: Eighteen
      intact human lumbar spine segments were tested for flexibility in a specially
      designed spine tester. Pure moments were applied in the three main planes, and
      range of motion and neutral zone were determined. Then, TLIF using the sickle
      shaped MOON cage (AMT AG), PLIF using the cubic Stryker cages (Stryker
      Orthopaedics), or PLIF using the threaded BAK cages (Zimmer Spinetech) was
      carried out and the specimens tested again. RESULTS: The stability after
      implantation of the MOON TLIF cage did not significantly differ from that after
      implantation of the cubic Stryker PLIF cages (P > 0.05). In contrast, the
      threaded BAK PLIF cages had a significantly higher primary stability than both
      the MOON TLIF and the Stryker PLIF cages in lateral bending, flexion, and
      extension (P < 0.05) but not in axial rotation (P > 0.05). CONCLUSIONS: In terms
      of its stabilizing effect, TLIF using the MOON cage can be recommended as an
      alternative to PLIF using the cubic Stryker cages. Compared with the threaded BAK
      PLIF cages, however, the MOON TLIF cage provides a lower primary stability in
      lateral bending, flexion, and extension.

PMID- 16284578
TI  - Anatomic changes in lateral spondylolisthesis associated with adult lumbar
      scoliosis.
AB  - STUDY DESIGN: Prospective consecutive series. OBJECTIVE: To analyze the anatomic
      changes in lateral spondylolisthesis. SUMMARY OF BACKGROUND DATA: Previous
      studies have focused on the correlation between lateral spondylolisthesis, and
      curve progression and pain. To our knowledge, there has not been any detailed
      report concerning anatomic changes in lateral spondylolisthesis. METHODS: We
      examined 24 consecutive patients (mean age 66 years), with lateral
      spondylolisthesis associated with lumbar scoliosis who had computerized
      tomography (CT) after myelography. Coronal reconstruction CT was used to measure
      the vertebral translation. Vertebral rotation was measured by the Aaro method
      using transaxial CT. RESULTS: The Cobb angle averaged 26 degrees (range 13
      degrees-75 degrees). Lateral spondylolisthesis was found most commonly at the
      lower-end vertebra. The cephalad-slipped vertebra rotated toward the convex side
      of the main curve, whereas the caudal vertebra rotated toward the convex side of
      the lumbosacral hemi (or fractional) curve below. Mean lateral translation and
      vertebral rotation were 7 mm and 8 degrees, respectively. There was a significant
      correlation between lateral translation and vertebral rotation (r = 0.49; P =
      0.018). The convex superior articular process of the caudal vertebra had
      compressed the nerve root laterally in 21 patients, of whom 10 had radicular
      pain. The concave, inferior articular process of the cephalad vertebra had
      compressed the dural sac posteriorly, and 2 patients had radicular pain.
      CONCLUSIONS: To our knowledge, this study has been the first attempt to analyze
      anatomic changes in lateral spondylolisthesis using CT. It may offer further
      insight into the pathogenesis of adult lumbar scoliosis.

PMID- 16284580
TI  - Anterior cervical screw extrusion leading to acute upper airway obstruction: case
      report.
AB  - STUDY DESIGN: Case report of late postoperative complication. SUMMARY OF
      BACKGROUND DATA: There have been a number of reports of migration and extrusion
      of cervical fusion instrumentation. The majority of such cases have a benign
      outcome. To our knowledge, cervical instrumentation extrusion resulting in
      prevertebral abscess and acute airway obstruction has not been reported. METHODS:
      A 56-year-old man who had undergone a prior C3-C6 anterior cervical decompression
      and fusion presented to a hospital with dysphagia and acute airway obstruction
      requiring an emergency tracheostomy. His neck radiograph showed that a C6 screw
      was missing compared to prior films. Magnetic resonance imaging showed a large
      prevertebral abscess anterior to C2-C7 causing complete upper airway obstruction.
      RESULTS: He underwent surgical drainage of the abscess and had a good neurologic
      recovery. CONCLUSIONS: We report a case of acute upper airway obstruction from
      prevertebral abscess, likely secondary to a loosened anterior cervical screw
      penetrating the prevertebral soft tissue. In contrast to case reports in the
      literature involving instrumentation extrusion with a usually benign outcome, our
      case presented with a life-threatening condition.

PMID- 16284579
TI  - The influence of fear avoidance beliefs on disability and quality of life is
      sparse in Spanish low back pain patients.
AB  - STUDY DESIGN: Correlation between previously validated questionnaires.
      OBJECTIVES: To assess the influence of fear avoidance beliefs (FAB) on disability
      and quality of life in Spanish low back pain (LBP) patients. SUMMARY OF
      BACKGROUND DATA: FAB has shown to be a major determinant of disability in LBP
      patients in Northern European and Anglo-Saxon cultural environments. There are no
      data on its influence on Latin-Mediterranean patients. METHODS: The study was
      done in 12 primary care and 9 hospital services from seven different regions of
      Spain, with 209 patients who were in a potentially active working situation and
      visited the National Health Service for LBP. None was excluded and the sample was
      balanced for acute, subacute, and chronic patients. On their first visit and 14
      days later, patients were given two independent Visual Analogue Scales (VAS) for
      LBP and leg pain, as well as the validated Spanish versions of the Fear Avoidance
      Beliefs (FABQ), Roland-Morris (RMQ), and SF-12 questionnaires. RESULTS:
      Correlations between LBP, leg pain, FABQ, disability, and quality of life were
      moderate on day 1 (r = 0.320-0.564) and stronger on day 15 (r = 0.457-0.637). All
      of them were statistically highly significant (P = 0.000). Regression models
      showed that LBP severity explains 33% of disability on day 1 and 20% on day 15,
      while FAB only explains 6% on day 1 and 2% on day 15. FAB does not explain mental
      quality of life. It explains only 5% of physical quality of life on day 1 and 4%
      on day 15. There was no interaction between FAB and chronicity, and FABQ values
      on day 1 did not predict disability or quality of life at day 15. CONCLUSIONS: As
      opposed to what has been shown in other cultural settings, FAB have virtually no
      clinical relevance in Spanish LBP patients who are treated in the National Health
      Service and who are in a potentially active working situation. The influence of
      FAB on disability is minimal and much less than that of pain severity, and their
      contribution to the patient's quality of life is irrelevant. Further studies
      should explore the potential value of FAB in other Latin-Mediterranean countries.

PMID- 16284581
TI  - Acute quadriparesis caused by calcification of the entire cervical ligamentum
      flavum in a white female--report of an unusual case and a brief review of the
      literature: case report.
AB  - STUDY DESIGN: Case report. OBJECTIVES: To describe an extremely unusual case of
      acute quadriparesis in a white female caused by calcification of the ligamentum
      flavum (LF) from C1 to T2, and to review briefly the pertinent literature.
      SUMMARY OF BACKGROUND DATA: Diseases characterized by abnormal calcium deposition
      on the spinal ligaments have an unclear etiology. The overwhelming majority of
      these cases has been reported in people of Asian descent and has a predilection
      for the thoracic spine. Multilevel involvement of the cervical LF in white
      patients is exceptionally rare. To our knowledge, complete calcification of the
      entire cervical LF has not been previously reported in the literature. METHODS:
      The history, physical examination, and radiographic studies of a 64-year-old
      white female with a history of scleroderma are described. The patient presented
      with neck pain and acute quadriparesis caused by spinal cord impingement by
      calcified cervical LF from C1 to T2. The patient underwent emergent C3-C7
      laminectomy and C2-C7 posterior spinal fusion. RESULTS: Operative intervention
      resulted in marked neurologic improvement and relief from neck pain.
      Histopathologic examination of the calcified LF showed that the deposits
      consisted of hydroxyapatite crystals exclusively with no heterotopic bone.
      However, kyphosis did develop in the patient after laminectomy. CONCLUSION: To
      our knowledge, this unusual case of complete calcification of the entire cervical
      LF has not previously been described. Multilevel laminectomy and fusion can
      improve neurologic function but may result in kyphosis.

PMID- 16284583
TI  - A prospective, randomized, double-blind study evaluating the efficacy of
      postoperative continuous local anesthetic infusion at the iliac crest bone graft
      site after spinal arthrodesis.
AB  - STUDY DESIGN: Parallel design, prospective, double-blind, randomized, controlled
      trial composed of two independent groups treated with a continuous infusion
      catheter (saline vs. Marcaine) placed into the iliac crest bone graft (ICBG)
      site. OBJECTIVE: To determine the effects of postoperative continuous local
      anesthetic agent infusion at the ICBG harvest site in reducing pain, narcotic
      demand and usage, and improving early postoperative function after spinal fusion.
      SUMMARY OF BACKGROUND DATA: Harvesting iliac crest bone has been shown to be a
      source of pain and morbidity. Long-term patient complaints may be more closely
      associated with the procurement of the iliac crest graft rather than the primary
      surgical site. METHODS: Thirty-seven patients were enrolled in a prospective,
      randomized, double-blind parallel-designed study after informed consent and IRB
      approval was obtained. Twenty-eight patients had ICBG harvested for lumbar
      arthrodesis and nine for cervical arthrodesis. During spinal arthrodesis surgery,
      patients were randomly assigned to receive 96 mL (2 mL/hr x 48 hours) of either
      normal saline (control group, n = 22) or 0.5% Marcaine (treatment group, n = 15)
      delivered via a continuous infusion catheter placed at the ICBG harvest site. All
      patients received Dilaudid PCA after surgery. Pain scores, narcotic
      use/frequency, activity level, and length of stay (LOS) were recorded.
      Physicians, patients, nursing staff, and statisticians were blinded to the
      treatment. RESULTS: Mean patient age was 60 years and similar between groups.
      Narcotic dosage, demand frequency, and mean VAS pain score were significantly
      less in the treatment (Marcaine) group at 24 and 48 hours (P < 0.05). The average
      LOS was 4.1 days with no difference between Marcaine or control groups. No
      complications were attributed to the infusion-catheter system. CONCLUSIONS:
      Continuous infusion of 0.5% Marcaine at the ICBG harvest site reduced
      postoperative parenteral narcotic usage by 50% and decreased overall pain scores.
      No complications were attributed to the infusion-catheter system. The use of
      continuous local anesthetic infusion at the iliac crest may help in alleviating
      acute graft-related pain, hastening patient recovery and improving short-term
      satisfaction.

PMID- 16284584
TI  - Transdermal fentanyl versus sustained release oral morphine in strong-opioid
      naive patients with chronic low back pain.
AB  - STUDY DESIGN: Open, randomized, parallel group multicenter study. OBJECTIVES: To
      compare the efficacy and safety of transdermal fentanyl (TDF) and sustained
      release morphine (SRM) in strong-opioid naive patients with chronic low back pain
      (CLBP). SUMMARY OF BACKGROUND DATA: Most studies of TDF and SRM have involved
      patients already receiving strong opioids. This is the first large-scale study
      focusing on strong-opioid naive patients with CLBP. METHODS: Adults with CLBP
      requiring regular strong opioid therapy received either TDF or SRM for 13 months.
      Starting doses were 25 microg/hr fentanyl patches every 72 hours or 30 mg oral
      morphine every 12 hours. Doses were adjusted according to response. Participants
      assessed pain relief and bowel function using weekly diaries. Other assessments,
      including quality of life, disease progression, and side effects, were made by
      patients and investigators. RESULTS: Data from 680 patients showed that TDF and
      SRM provided similar levels of pain relief, but TDF was associated with
      significantly less constipation than SRM, indicating a greater likelihood of
      satisfactory pain relief without unmanageable constipation for patients receiving
      TDF. Other ratings were similar for TDF and SRM, but TDF provided greater relief
      of pain at rest and at night. CONCLUSIONS: TDF and SRM provided equivalent levels
      of pain relief, but TDF was associated with less constipation. This study
      indicates that sustained-release strong opioids can safely be used in strong
      opioid naive patients.

PMID- 16284585
TI  - Spinal neuropeptide responses in persistent and transient pain following cervical
      nerve root injury.
AB  - STUDY DESIGN: Behavioral and immunohistochemical analysis in rat models of
      persistent and transient allodynia. OBJECTIVES: To examine separate cervical
      nerve root injuries (compression, transection) for producing behavioral
      hypersensitivity and investigate spinal neuropeptides to understand relationships
      to pain symptoms. SUMMARY OF BACKGROUND DATA: Mechanical cervical nerve root
      injury can be a source of neck pain. Painful lumbar radiculopathy models show
      that different nerve root ligation intensities produce differential allodynia
      responses. Spinal neuropeptides can mediate pain responses. Yet, little is known
      about their contributions to pain in the cervical spine. METHODS: Rats underwent
      separate procedures on the right C7 nerve roots: transection (n = 12), 10-gf
      compression for 15 minutes (n = 11), or sham (n = 5). Ipsilateral forepaw
      mechanical allodynia was measured after surgery for 7 days. C7 spinal cord tissue
      was analyzed by immunohistochemistry for substance P and calcitonin gene-related
      peptide (CGRP) expression on days 1 and 7 for each injury; densitometry
      quantified immunoreactivity in lamina I of the ipsilateral dorsal horn. RESULTS:
      Both injuries immediately produced significant increases in allodynia.
      Sensitivity was sustained following root compression, and at day 7, was not
      different from day 1. By day 7 after transection, allodynia had returned to
      baseline and sham levels, significantly decreasing from day 1 (P = 0.0012).
      Spinal substance P and CGRP were increased over normal at day 1 for both injuries
      and decreased with time for CGRP after transection, which paralleled behaviors.
      For individual rats, substance P was significantly (P < 0.001) correlated with
      CGRP expression for both injuries. CONCLUSIONS: Compression and transection of
      the cervical nerve root produce different forepaw allodynia responses, with
      persistent and transient sensitivity, respectively. Spinal neuropeptide
      expression in these models parallels this sensitivity, suggesting their potential
      role in pain symptoms.

PMID- 16284586
TI  - Bone ingrowth in retrieved Bryan Cervical Disc prostheses.
AB  - STUDY DESIGN: Explant analysis for bone ingrowth of retrieved cervical disc
      prosthesis in chimpanzees and humans. OBJECTIVES: To assess the bone ingrowth
      into retrieved Bryan Cervical Discs. SUMMARY OF BACKGROUND DATA: Bone ingrowth in
      cervical disc prosthesis has not been documented in the literature. METHODS:
      Chimpanzee: Two chimpanzees underwent placement of the Bryan disc at C3-C4 and 3
      months later had explantation and interbody fusion. Human: Two patients had
      removal of their Bryan disc and interbody fusion for failure to resolve symptoms
      at 8 and 10 months. The explants were analyzed for bone ingrowth. RESULTS:
      Chimpanzee: Histologic analysis showed bony ingrowth through the interstices of
      the porous coating and apposition ranging from 10% to 50% of toluidine blue
      stained sections. New ingrowth, rather than bony impaction, was confirmed with
      fluorochrome-labeled sections Human: Bone ingrowth was a mean of 30.1% (12% SD).
      No difference was observed between peripheral, intermediate, or central
      locations. CONCLUSIONS: Adequate bony apposition was found in all primate device
      to-vertebral body interfaces. Human retrievals also demonstrated significant
      ingrowth in all four surfaces. This compares with hip and knee arthroplasty
      percent ingrowth rates of 10% to 30%. All implants had stable fixation judged by
      radiographs and at the time of implant removal.

PMID- 16284587
TI  - Hypoxia activates MAPK activity in rat nucleus pulposus cells: regulation of
      integrin expression and cell survival.
AB  - OBJECTIVE: The aim of the present study was to investigate whether activation of
      MAPK subtypes ERK and p38 influences integrin expression and promotes nucleus
      pulposus cell survival in hypoxia. SUMMARY OF BACKGROUND DATA: We have recently
      shown that in a low oxygen environment, rat nucleus pulposus cells activate
      phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein
      kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways.
      However, the role of these signaling pathways in regulating cell matrix
      interactions is not known. METHODS: Rat nucleus pulposus cells were cultured in
      hypoxia (2% O2) or normoxia (20% O2). Western blotting and kinase assay were used
      to analyze expression of MAPK signaling molecules. Cell attachment to collagen
      was studied using an adhesion assay, whereas flow cytometry and RT-PCR were
      performed to quantify integrin receptor expression. RESULTS: In a hypoxic
      environment (2% O2), rat nucleus pulposus cells showed a persistent
      phosphorylation of p38 and ERK proteins; pERK catalyzed the phosphorylation of
      Elk1-Gst fusion protein. When ERK activity was blocked, cell adhesion to Type II
      collagen, one of the major extracellular matrix proteins in the nucleus pulposus
      tissue, was impaired. A similar inhibitory effect on collagen adhesion was
      observed when nucleus pulposus cells were treated with an antibody to alpha2
      integrin. Furthermore, when ERK activity was inhibited, there was a decrease in
      alpha2 integrin mRNA expression. In contrast to ERK, inhibition of p38 activity
      did not modulate alpha2 integrin subunit mRNA expression. Likewise, inhibition of
      ERK, but not p38, resulted in downregulation of nucleus pulposus alpha2 integrin
      protein levels and blocked cell survival in hypoxia. CONCLUSIONS: Hypoxia
      activated MAPK signaling pathway activity in nucleus pulposus cells. ERK, but not
      p38, regulated alpha2 integrin expression and cell survival.

PMID- 16284588
TI  - Stimulation of gene expression and loss of anular architecture caused by
      experimental disc degeneration--an in vivo animal study.
AB  - STUDY DESIGN: An external compression model was used to evaluate gene and protein
      expression in intervertebral discs with moderate disc degeneration. OBJECTIVE: To
      determine messenger ribonucleic acid and protein expression levels of relevant
      disc components. SUMMARY OF BACKGROUND DATA: An animal model of mechanically
      induced disc degeneration was developed and characterized histologically.
      However, little is known at the molecular level in moderate disc degeneration.
      METHODS: There were 8 New Zealand white rabbits subjected to monosegmental
      posterior compression to induce moderate disc degeneration. Twelve animals served
      as controls or sham controls. Discs were analyzed using immunohistochemistry for
      collagen type 1 (COL1), COL2, aggrecan, and bone morphogenetic protein-2/4 (BMP
      2/4). For gene analysis, conventional and quantitative polymerase chain reactions
      were used for COL1A2, COL2A1, aggrecan, BMP-2, biglycan, decorin, osteonectin,
      fibromodulin, fibronectin, matrix metalloproteinase-13 (MMP-13), and tissue
      inhibitor of MMP-1. Gene expression for nontreated, sham-treated, and compressed
      discs was quantified in relation to the housekeeping gene glyceraldehyde-3
      phosphate dehydrogenase. RESULTS: Immunohistochemistry of compressed discs showed
      a loss of anular architecture, and a significant reduction of BMP-2/4 and COL2
      positive cells. Gene expression analysis showed a significant up-regulation of
      COL1A2, osteonectin, decorin, fibronectin, tissue inhibitor of MMP-1, BMP-2, and
      MMP-13 in compressed discs. CONCLUSIONS: Experimental moderate disc degeneration
      is characterized by a loss of BMP-2/4 and COL2 positive cells, although gene
      expression of disc constituents, catabolic enzymes, and growth factors is
      stimulated to reestablish disc integrity.

PMID- 16284589
TI  - Alendronate inhibits spine fusion in a rat model.
AB  - STUDY DESIGN: A posterolateral lumbar fusion model in rats. OBJECTIVE: To study
      the effects of alendronate on posterolateral lumbar fusion in rats. SUMMARY OF
      BACKGROUND DATA: To our knowledge, there are no studies that show a significant
      inhibition of manual palpation-assessed spine fusion by alendronate. METHODS: A
      total of 75 Sprague-Dawley rats underwent intertransverse fusion with 7-tailbone
      autograft at L4-L5. Animals received saline (control), alendronate equivalent to
      human dose (dose1, 5 microg/kg/day), or 10 times the human dose (dose10, 50
      microg/kg/day) via subcutaneous osmotic pumps starting the day of surgery. Eight
      weeks after surgery, animals were euthanized, and fusion was assessed by manual
      palpation. Radiographic area and optical density of fusion masses were
      calculated. Histomorphometry was used to assess the percentage area of fusion
      masses occupied by bone or marrow tissues. RESULTS: Manual palpation fusion rates
      were lower in alendronate groups (50% and 40%, respectively) than in the control
      group (95%, P = 0.002). Interobserver and intraobserver kappa values were high
      (0.97-1.00). There were dose-dependent and statistically significant (P < 0.001)
      increases in fusion mass area and optical density with increasing alendronate
      dose. Fusion masses in dose10 animals had significantly higher percent area of
      bone tissue (P = 0.01) and lower percent area of marrow elements (P < 0.001) when
      compared to control animals. CONCLUSIONS: Alendronate inhibits spine fusion in
      rats. Fusion masses in alendronate-treated animals appeared radiographically
      larger and denser than those in control animals despite lower fusion rates.
      Quantitative histomorphometry confirmed that alendronate inhibited bone graft
      resorption and incorporation. We recommend that patients undergoing spine
      arthrodesis should not take alendronate until fusion is achieved.

PMID- 16284590
TI  - Biomechanical analysis of a new concept: an add-on dynamic extension plate for
      adjacent-level anterior cervical fusion.
AB  - STUDY DESIGN: A biomechanical study on a pneumatically controlled 7-axis spine
      simulator using Delron and human cadaveric spine models. OBJECTIVES: To compare
      the biomechanical properties of an anterior cervical extension plate with
      comparable-length anterior cervical plates. SUMMARY OF BACKGROUND DATA: Adjacent
      level anterior cervical surgery next to a previously plated fusion can be
      technically challenging because of scarring from the previous surgery and the
      extensive exposure potentially required. An extension plate that attaches to an
      existing cervical plate could make adjacent-level cervical surgery less
      problematic. METHODS: Flexibility and load sharing were tested in 18 delron
      models and 10 cadaveric spines. An extension plate (E-plate, Aesculap,
      Tuttlingen, Germany) at C5-C6 was attached to a single-level plate (ABC plate,
      Aesculap) at C4-C5 and compared with a two-level plate (ABC plate) spanning C4
      C6. Segmental motion was monitored with optical tracking, and interbody graft
      load was measured with a load cell. Statistical analysis was performed with a
      Student's t test'. RESULTS: In the delron models, both constructs displayed
      virtually 100% load sharing for the full interbody graft and subsidence models,
      and range of motion in flexion-extension or axial rotation was not statistically
      significantly different. The failure mode for the extension plate was lateral
      bending. In the cadaveric spines, load sharing, range of motion, and stiffness
      were not statistically significantly different between constructs. CONCLUSIONS:
      This extension plate appears to be biomechanically equivalent to the ABC cervical
      plates with which it was compared in this study.

PMID- 16284591
TI  - Pedicle screw fixation of the thoracic spine: an in vitro biomechanical study on
      different configurations.
AB  - STUDY DESIGN: An in vitro biomechanical study of different pedicle screw
      configuration usage on the thoracic spine using a cadaveric model. OBJECTIVES: To
      investigate the degree of motion afforded different pedicle screw configurations
      in the thoracic spine using a cadaveric model with 2 different degrees of
      intrinsic stability. SUMMARY OF BACKGROUND DATA: Recently, thoracic pedicle
      screws have become an alternative to hook and wire fixation, and have gained
      popularity. Clinically, pedicle screw use has ranged from application to every
      segment, to skipping every other level. There exists no clear consensus as to
      which strategy is most appropriate. METHODS: The load-displacement behavior of 6
      different constructs was determined on 8 fresh frozen cadaver spine specimens (T4
      T12). Each construct was evaluated on 2 destabilization models, including minimum
      destabilization (bilateral facetectomy) and maximum destabilization (facetectomy
      and annulotomy). Pure moments were applied, and the resultant range of motion for
      each scenario was determined. RESULTS: Facetectomy did not significantly
      destabilize the thoracic spine. Annulotomy and facetectomy created gross
      instability that rendered testing of this destabilization model impossible. All
      constructs significantly reduced the range of motion compared to intact or
      facetectomized specimens (P < or = 0.001). When different constructs were
      compared to each other, a pattern of continuously increasing stability emerged,
      with the "maximum" construct being the most stable and "minimum" configuration
      being the least, with varying degrees of statistical significance. CONCLUSIONS:
      Our results suggest that the most important factor for the acute postoperative
      stability of spinal fixation is the degree of preoperative or iatrogenic
      destabilization. The minimum amount of pedicle screws provides adequate stability
      when there is minimal destabilization of the spine. On the other hand, when
      anterior column release has been performed or instability exists before surgery,
      segmental pedicle screw fixation may be necessary to achieve adequate stability.

PMID- 16284592
TI  - Intermittent pneumatic compression stocking prophylaxis against deep venous
      thrombosis in anterior cervical spinal surgery: a prospective efficacy study in
      200 patients and literature review.
AB  - STUDY DESIGN: Intermittent pneumatic compression stockings (IPC) alone were
      prospectively used to avoid deep venous thrombosis (DVT) and pulmonary embolism
      (PE) in 100 consecutive patients undergoing single-level anterior
      corpectomy/fusion (ACF) and in 100 patients having multilevel ACF/posterior
      fusion. OBJECTIVES: To determine the optimal prophylaxis against DVT and PE for
      patients undergoing anterior cervical spinal surgery. BACKGROUND DATA: Mini
      heparin and low-dose heparin prophylaxis in neurosurgery poses a 2% to 4% risk of
      major postoperative hemorrhage with resultant neurologic sequelae. METHODS:
      Prophylaxis consisted of IPC alone. Doppler studies of the lower extremities were
      routinely obtained 2 days after surgery. Single-level ACF (100 patients)
      addressed two-level disc disease, spondylostenosis, and ossification of the
      posterior longitudinal ligament (OPLL). One hundred patients undergoing
      multilevel ACF (3+ levels) with posterior fusion (C2-T1) exhibited
      OPLL/spondylostenosis. RESULTS: One patient undergoing single-level ACF developed
      DVT/PE 6 days after surgery; she exhibited Factor V Leiden mutation
      (hypercoagulability syndrome). Although 7 patients undergoing circumferential
      surgery developed DVT 2 to 14 days following surgery (mean, 7.15 days), only two
      clots localized in the iliac veins resulted in PEs (days 10 and 14 after
      surgery). CONCLUSIONS: IPCs were as effective for prophylaxis against DVT/PE for
      100 patients undergoing single-level ACF and for 100 having circumferential
      procedures as existing therapies (mini-heparin and low-dose heparin), without the
      risk of hemorrhage. However, the 1% and 2% respective rates of PE were comparable
      to frequencies of PE encountered in other cranial/spinal series using mini
      heparin and/or low-dose heparin regimens but avoided the 2% to 4% risk of major
      postoperative hemorrhage.

PMID- 16284593
TI  - Axial symptoms after cervical laminoplasty with C3 laminectomy compared with
      conventional C3-C7 laminoplasty: a modified laminoplasty preserving the
      semispinalis cervicis inserted into axis.
AB  - STUDY DESIGN: Results of C4-C7 laminoplasty with C3 laminectomy and C3-C7
      laminoplasty were compared. OBJECTIVES: To clarify prospectively whether the
      modified laminoplasty preserving the semispinalis cervicis inserted into C2 could
      reduce the axial symptoms compared with conventional laminoplasty reattaching the
      muscle to C2. SUMMARY OF BACKGROUND DATA: Intraoperative damage of the
      semispinalis cervicis is relevant to the development of axial symptoms after
      laminoplasty. In C3-C7 laminoplasty, however, it is difficult to preserve the
      muscle insertion into C2 while opening the C3 lamina. METHODS: The axial symptoms
      of 40 patients (Group A) with C4-C7 laminoplasty with C3 laminectomy were
      compared with those of 16 patients (Group B) with C3-C7 laminoplasty. The cross
      sectional areas of the cervical posterior muscles were measured on magnetic
      resonance images. RESULTS: The number of patients with no postoperative axial
      symptoms increased (P = 0.035) from 19% to 52.5%, and the number of patients
      whose symptoms worsened after surgery decreased (P = 0.020) from 50% to 17.5%.
      The average atrophy rate of cross-sectional area was smaller (P < 0.001) in Group
      A (2.4%) than in Group B (10.8%). CONCLUSIONS: This method was less invasive to
      the cervical posterior muscles than C3-C7 laminoplasty. This is an effective
      procedure for preventing postoperative axial symptoms.

PMID- 16284594
TI  - The validity of Lenke criteria for defining structural proximal thoracic curves
      in patients with adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Retrospective series. OBJECTIVE: To delineate the efficiency of
      using Lenke criteria during the decision of whether to include the proximal
      thoracic curve into instrumented fusion or not in patients with adolescent
      idiopathic scoliosis (AIS) treated with posterior translational instrumentation.
      SUMMARY OF BACKGROUND DATA: Lenke and colleagues classified the curves of
      patients with AIS and assigned the term "structural" or "nonstructural" to each
      curve. However, there is still not much consensus on the definition of structural
      proximal thoracic curve, and structurality criteria for proximal thoracic curve
      have not been validated yet. METHODS: Inclusion criteria were: (1) patients with
      AIS treated with a posterior translational instrumentation system and older than
      10 years; (2) nonstructural upper thoracic curves (side bending Cobb <25 degrees
      and T2-T5 kyphosis <+20 degrees); and (3) a minimum of 2 years of follow-up. A
      total of 37 consecutive patients, including 6 males and 31 females, with AIS that
      was treated, with an average age of 15 years (range 11-24) and average follow-up
      of 55 months (range 24-90) were studied. For radiologic evaluation of the
      patients, preoperative, postoperative, and latest follow-up radiographs were
      used. There were 2 groups constructed according to the involvement of proximal
      thoracic curve into instrumented fusion. Group 1 included those patients who
      underwent uppermost extent of the instrumentation, either T2 or T3, indicating
      inclusion of proximal thoracic curve into instrumentation. Group 2 included
      individuals who underwent uppermost extent of the instrumentation at T4 or lower,
      indicating partial or no inclusion of the proximal thoracic curve into
      instrumented fusion. Radiographic evaluation included the measurement of proximal
      thoracic, main thoracic, and thoracolumbar-lumbar curves. On the lateral
      radiographs, sagittal Cobb angles of T2-T5, T5-T12, and T10-L2 were measured.
      Difference between right and left coracoid process heights, clavicle angle, and
      T1 tilt were determined for assessment of shoulder balance. RESULTS: The 2 groups
      were statistically equivalent in terms of age at surgery, follow-up time,
      preoperative proximal thoracic and main thoracic, and their corresponding side
      bending curve magnitudes, as well as the parameters related to shoulder balance
      before surgery (P > 0.05). The 2 groups were also statistically equivalent
      regarding immediate postoperative and latest follow-up proximal thoracic and main
      thoracic, and parameters related to shoulder balance (P > 0.05). CONCLUSION: It
      was observed that the Lenke description for structurality of proximal thoracic
      curves can effectively determine which curves need fusion and which curves do
      not. Because there was no difference among inclusion of a nonstructural proximal
      thoracic curve into fusion or solely fusing the main thoracic curve in terms of
      outcomes, extension of fusion to T2 or T3 is unnecessary. In this patient
      population, the question of what the upper extent of instrumentation should be
      could not be answered.

PMID- 16284595
TI  - The use of magnetic resonance imaging to evaluate lumbar muscle activity during
      trunk extension exercise at varying intensities.
AB  - STUDY DESIGN: Descriptive, repeated measures analysis of exercise-induced changes
      in lumbar muscle transverse relaxation time (T2). OBJECTIVES: To use muscle
      functional magnetic resonance imaging (MRI) to characterize the activity levels
      and recruitment patterns of the lumbar extensor muscles during trunk extension
      exercise over 3 intensities. SUMMARY OF BACKGROUND DATA: Contrast shifts in T2
      are indicative of skeletal muscle activity during resistance exercise and are
      used to characterize the function of a variety of muscles. The use of muscle
      functional MRI for the lumbar muscles has been limited. METHODS: In 11 healthy
      participants, T2 was calculated for the lumbar quadratus lumborum, iliocostalis
      lumborum, longissimus thoracis, and multifidus at rest and following dynamic
      trunk extension exercise at 3 exercise intensities (40%, 50%, and 70% peak
      intensity). RESULTS: The multifidus displayed the largest T2 increase at each of
      the 3 exercise intensities, followed by the erector spinae and, finally, the
      quadratus lumborum. At the lowest intensity, the medial erector spinae
      (longissimus thoracis) displayed a higher T2 increase than the lateral group
      (iliocostalis lumborum), while at the higher intensities, this pattern was
      reversed. In general, the T2 increase was higher during exercise at 50% and 70%
      intensities than at 40%, while there was no difference in T2 increase between 50%
      and 70%. CONCLUSIONS: Muscle functional MRI can be used to characterize lumbar
      muscle function during trunk extension exercise. The levels and recruitment
      patterns of the lumbar extensors, as measured by muscle T2 shifts, vary with
      exercise intensity. Future research is needed to assess the mechanism of the
      nonlinear relationship between T2 shifts and exercise intensity, and to clarify
      the effects of fatigue and the order of exercise presentation on the T2 response
      of the lumbar extensors.

PMID- 16284597
TI  - An extreme lateral access for the surgery of lumbar disc herniations inside the
      spinal canal using the full-endoscopic uniportal transforaminal approach
      technique and prospective results of 463 patients.
AB  - STUDY DESIGN: Prospective study of patients with lumbar disc herniations who were
      operated on with a full-endoscopic uniportal transforaminal approach using an
      extreme lateral access. OBJECTIVES: To examine the technical possibilities of an
      extreme lateral access for full-endoscopic uniportal transforaminal surgery of
      lumbar disc herniations within the spinal canal. Also, to assess sufficient
      decompression, and the advantages and disadvantages of the minimally invasive
      procedure. SUMMARY OF BACKGROUND DATA: Conventional prolapsed disc operations can
      result in consecutive damage as a result of traumatization. The usual
      transforaminal access is posterolateral, and is associated with problems in
      reaching the epidural space directly with unhindered vision and, thus, with
      problems of sufficient decompression in lumbar disc herniations within the spinal
      canal. METHODS: A total of 463 patients were observed for 1 year. In addition to
      general and specific parameters, the following measuring instruments were used:
      visual analog scale, German version North American Spine Society Instrumentarium,
      Oswestry low back pain disability questionnaire. RESULTS: There were no
      complications. Of the patients, 81% reported no longer having leg pain, and 14%
      had occasional pain. There was no worsening. The results were constant and are
      equal to those of conventional procedures. No patients presented with neural
      scarring; 7% had recurrence of the prolapse. The extreme lateral access was
      necessary to reach the sequestered material. CONCLUSIONS: The technique presented
      is an adequate and safe alternative to conventional procedures, and has the
      advantages of a truly minimally invasive procedure. The extreme lateral access is
      required for the indications described. There are clear limitations outside these
      indications. The possibility of selecting an access from posterolateral to
      extreme lateral now enables surgery of lumbar disc herniations inside and outside
      the spinal canal.

PMID- 16284596
TI  - Dysphagia after anterior cervical decompression and fusion: prevalence and risk
      factors from a longitudinal cohort study.
AB  - STUDY DESIGN: Retrospective analysis of the incidence and prevalence of dysphagia
      after anterior cervical decompression and fusion (ACDF). OBJECTIVES: To examine
      the incidence and prevalence of dysphagia after ACDF, determine possible
      associated patient and procedural characteristics, and examine dysphagia's impact
      on long-term health status and function. SUMMARY OF BACKGROUND DATA: Dysphagia is
      a common early complaint after ACDF, but the risk factors associated with its
      development are not understood. METHODS: Telephone surveys (Cervical Spine
      Outcomes Questionnaire) and clinical assessments (Oswestry Neck Disability Scale
      and SF-36) were used to evaluate 454 patients who had undergone ACDF at one of 23
      nationwide sites for individual and procedure characteristics that might
      contribute to dysphagia. RESULTS: Of the 454 patients, 30% reported dysphagia at
      the 3-month assessment (incident cases). The incidence of new complaints of
      dysphagia at each follow-up point was 29.8%, 6.9%, and 6.6% at 3, 6, and 24
      months, respectively. Dysphagia persisted at 6 and 24 months in 21.5% and 21.3%
      of patients, respectively. The risk of dysphagia increased with number of
      surgical vertebral levels at 3 months: 1 level, 42 of 212 (19.8%); 2 levels, 50
      of 150 (33.3%); 3+ levels, 36 of 92 (39.1%). Patients reporting dysphagia at 3
      months had a significantly higher self-reported disability and lower physical
      health status at subsequent assessments. CONCLUSION: Duration of preexisting pain
      and the number of vertebral levels involved in the surgical procedure appear to
      influence the likelihood of dysphagia after ACDF.

PMID- 16284598
TI  - The physician as disability advisor for patients with musculoskeletal complaints.
AB  - STUDY DESIGN: Literature review. OBJECTIVES: To review the literature about the
      performance of physicians as mediators of temporary and permanent disability for
      patients with chronic musculoskeletal complaints. To assess specifically the
      nature and variance of recommendations from physicians, factors influencing
      physician performance, and efforts to influence physician behavior in this area.
      SUMMARY OF BACKGROUND DATA: While caring for patients with musculoskeletal
      injuries, physicians are often asked to recommend appropriate levels of activity
      and work. These recommendations have significant consequences for patients'
      general health, employment, and financial well-being. METHODS: Medical literature
      search. RESULTS: Physician recommendations limiting activity and work after
      injury are highly variable, often reflecting their own pain attitudes and
      beliefs. Patients' desires strongly predict disability recommendations (i.e.,
      physicians often acquiesce to patients' requests). Other influences include
      jurisdiction, employer, insurer, and medical system factors. The most successful
      efforts to influence physician recommendations have used mass communication to
      influence public attitudes, while reinforcing the current standard of practice
      for physicians. CONCLUSIONS: Physician recommendations for work and activity have
      important health and financial implications. Systemic, multidimensional
      approaches are necessary to improve performance.

PMID- 16284599
TI  - Intracameral phenylephrine to prevent floppy iris syndrome during cataract
      surgery in patients on tamsulosin.
AB  - PURPOSE: To describe the use of intracameral phenylephrine to prevent the floppy
      iris syndrome seen in patients who are on the drug tamsulosin for benign
      prostatic hypertrophy, during cataract surgery. SETTING: Prince Charles Eye Unit,
      King Edward VII Hospital, Windsor, Berkshire, UK. METHOD: Seven patients who were
      on systemic tamsulosin for benign prostatic hypertrophy received intracameral
      phenylephrine before capsulorexhis during their cataract surgery. RESULTS: There
      was a significant reduction in the amount of mobility of the iris, reduction in
      the expected fluttering, and sustained papillary dilatation.
      ConclusionIntracameral phenylephrine is a simple and effective tool to prevent
      the effects of floppy iris syndrome in those patients undergoing cataract surgery
      who are on systemic tamsulosin.

PMID- 16284600
TI  - Age-related maculopathy and cataract surgery outcomes: visual acuity and health
      related quality of life.
AB  - PURPOSE: To assess visual acuity (VA) and health-related quality of life (HRQoL)
      outcomes in patients with and without age-related maculopathy (ARM) after
      cataract surgery. METHODS: Patients aged 60+ years who had undergone cataract
      surgery at the Westmead Hospital during 2001-2003 were re-examined 1-3 years
      after surgery. Tests included VA and assessment of visual- and HRQoL using
      standardised questionnaires (VF-14, SF-12). Preoperative comorbidity data were
      collected from medical records. Poor surgical outcomes (VA<6/12; no VA
      improvement; lowest quintile of VF-14, SF-12 scores) were compared in patients
      with and without ARM, adjusting for age, sex, preoperative systemic
      comorbidities, ocular comorbidities and surgical or postoperative complications.
      RESULTS: Of 622 surviving patients, 454 (73%) were followed up for a mean period
      of 2.8 years. Similar proportions with VA>or=6/12 were observed in patients with
      (80.2%) and without (88.8%) pre-existing ARM. Preoperative early ARM was only
      associated with slightly lower mean VF-14 scores (87.64 with vs 92.58 without
      ARM, P=0.01). Increasing age and preoperative ocular comorbidities were
      associated with all poor outcomes measured. Low SF-12 scores were associated with
      preoperative systemic comorbidities. CONCLUSION: Our study documents favourable
      cataract surgical outcomes 1-3 years after cataract surgery in patients with
      preoperative ARM.

PMID- 16284601
TI  - Effectiveness of emergency argon laser retinopexy performed by trainee doctors.

PMID- 16284602
TI  - Indocyanine green angiography in diffuse unilateral subacute neuroretinitis.

PMID- 16284603
TI  - The aetiology in paediatric aphakic glaucoma.
AB  - PURPOSE: To investigate the causes of glaucoma in children following removal of
      cataracts. METHODS: In total, 24 patients (37 eyes) with uncomplicated congenital
      cataracts who developed glaucoma following cataract removal were studied
      retrospectively. Cataract morphology, surgical technique, postoperative
      complications, time to glaucoma onset, gonioscopic findings, the presence of
      microcornea, and the histopathologic characteristics of the filtration angle in
      one case were the studied parameters. RESULTS: We found a bimodal onset of
      glaucoma. Early-onset glaucoma occurred at a mean age of 6 months in 15 eyes and
      delayed-onset glaucoma at a mean age of 12 years in 22 eyes. Early-onset glaucoma
      was significantly (P=0.018) more likely to be due to angle closure. With delayed
      onset glaucoma, the filtration angle is open in 86% of eyes and significantly
      (P=0.006) more eyes in the delayed-onset group had microcornea. CONCLUSIONS:
      Performing cataract surgery very early in life in microphthalmic eyes and leaving
      residual lens material increases the risk for glaucoma. We recommend a
      prophylactic iridectomy in eyes at risk for pupillary block. Eyes with delayed
      onset glaucoma have open filtration angles but with findings consistent with
      incomplete development of filtration structures. Early age at cataract extraction
      and microcornea are risk factors for delayed-onset glaucoma.

PMID- 16284604
TI  - Methodology of evaluating conjunctival appearance following sub-Tenon's block for
      phacoemulsification cataract surgery.

PMID- 16284605
TI  - Determination of vitreous interleukin-1 (IL-1) and tumour necrosis factor (TNF)
      levels in proliferative diabetic retinopathy.
AB  - We measured interleukin-1 beta (IL-1beta) and tumour necrosis factor-alpha (TNF
      alpha) in the vitreous humour and serum of patients with proliferative diabetic
      retinopathy (PDR), in order to determine the role of these cytokines in the
      pathogenesis of the disease. Vitreous and serum samples were collected from 21
      patients with PDR who were undergoing pars plana vitrectomy. Control vitreous
      samples were obtained from cadavers and control serum samples from healthy
      subjects. The cytokines were measured by enzyme-linked immunosorbent assay.
      Vitreous IL-1beta and TNF-alpha concentrations in patients with PDR exceeded
      those of controls (P<0.05), as did serum IL-1beta and TNF-alpha. We suggest that
      increased vitreous IL-1beta and TNF-alpha levels may play a significant role in
      the pathogenesis of PDR, which features abnormal cell proliferation and
      neovascularisation.

PMID- 16284607
TI  - Decreased risk of acute gastrointestinal toxicity when substituting methotrexate
      with mycophenolate mofetil in the prevention of graft-versus-host disease in stem
      cell transplantation following myeloablative conditioning regimens.

PMID- 16284609
TI  - Long-term remission after autologous peripheral blood stem cell transplantation
      for relapsed intravascular lymphoma.

PMID- 16284608
TI  - Comparable results in patients with acute lymphoblastic leukemia after related
      and unrelated stem cell transplantation.
AB  - We report the results of 84 patients with ALL after related (n = 46) or unrelated
      (n = 38) allogeneic SCT. Mean recipient age was 23 years (range: 1-60) and median
      follow-up was 18 months (range: 1-133). Forty-three patients were transplanted in
      CR1; 25 in CR2 or CR3; four were primary refractory; four in PR; eight in
      relapse. The conditioning regimen consisted of TBI/VP16/CY (n = 76), TBI/VP16 (n
      = 2), TBI/CY (n = 2), Bu/VP16/CY (n = 4). The OS at 3 years was 45% (44%
      unrelated, 46% related). Univariate analysis showed a significantly better OS for
      patients <18 years (P=0.03), mismatched sex-combination (P = 0.03), both with a
      stronger effect on increasing OS after unrelated SCT. Factors decreasing TRM were
      patient age <18 years (P = 0.004), patient CMV-seronegativity (P = 0.014), female
      recipient (P = 0.04). There was no significant difference in TRM and the relapse
      rate was similar in both donor type groups. Multivariate analysis showed that
      factors for increased OS which remained significant were mismatched sex
      combination (RR: 0.70,95% CI: 0.51-0.93, P = 0.015), patient age < 18 years (RR:
      0.66, 95% CI: 0.47-0.93, P = 0.016). A decreased TRM was found for female
      patients (RR: 0.56, 95% CI: 0.33-0.98, P=0.042), negative CMV status of the
      patient (RR: 0.57, 95% CI: 0.36-0.90, P = 0.015). Unrelated stem cell
      transplantation for high-risk ALL patients with no HLA-compatible family donor is
      justifiable.

PMID- 16284610
TI  - Production of IL-10 by alloreactive sibling donor cells and its influence on the
      development of acute GVHD.
AB  - Graft-versus-host disease (GVHD) is a major complication of allogeneic
      hematopoietic stem cell transplantation. Pretransplant conditioning regimes cause
      release of proinflammatory cytokines that stimulate alloreactive donor T cells to
      attack recipient tissues. IL-10 has been shown to directly downregulate CD4+ T
      cells by suppressing IL-2 secretion and a critical role played by regulatory T
      cells has been demonstrated in animal models. One defining cytokine profile for
      regulatory T cells is the production of IL-10. Release of specific cytokines (IL
      10, IL-4 and IFN-gamma) was detected using ELISPOT technology, following
      stimulation of donor peripheral blood mononuclear cells by recipient (human
      leukocyte antigen-matched sibling) alloantigen or by mitogen. Correlation between
      the frequency of cytokine-releasing cells and the development of acute GVHD was
      investigated. A high frequency of donor cells producing IL-10 in response to
      recipient alloantigen stimulation correlated with absence of acute GVHD after
      bone marrow transplant (BMT), while low frequency was strongly associated with
      severe GVHD. This study presents strong evidence that estimating the frequency of
      donor alloreactive cells producing IL-10 in response to recipient antigens will
      provide valuable information prior to BMT regarding potential transplant outcome.

PMID- 16284611
TI  - Purging of murine erythroblastic leukemia by ZnPcS2P2-based-photodynamic therapy.
AB  - A key point for successful transplantation of autologous hematopoietic stem cells
      in the treatment of leukemia is the purging technique, of which photodynamic
      therapy (PDT) proved effective and promising. The aim of this study was to
      evaluate the purging effect of a novel amphipathic photosensitizer, di-sulfo-di
      phthalimidomethyl phthalolcyanine zinc (ZnPcS2P2)-based PDT (ZnPcS2P2-PDT) on
      murine erythroblastic leukemic EL9611 cells. Bone marrow cells (BMC), harvested
      from normal BALB/c mice, were contaminated with variable EL9611 cells. Cell
      suspensions were incubated with 4 microg/ml ZnPcS2P2 for 5 h and then exposed to
      2.1 J/cm2 irradiation by a semiconductor laser 670 nm. Lethally irradiated
      recipient BALB/c mice (7 Gy) received syngeneic bone marrow transplantation with
      purged or nonpurged cell mixtures of 10(7) BMC contaminated with variable numbers
      (10(2)-10(5)) of EL9611 cells. All of the irradiated controls died due to sepsis.
      All of the mice injected with nonpurged cell mixtures developed leukemia and
      died, whereas the mice transplanted with ZnPcS2P2-PDT-treated mixtures had a
      longer survival time, and the fewer leukemic cells there were in the cell
      mixtures, the higher the leukemia-free survival rate. We conclude that ZnPcS2P2
      PDT could purge leukemic cells from bone marrow autografts but could retain
      sufficient progenitor cells for the hematopoietic activity.

PMID- 16284612
TI  - Vitamin K deficiency in children pre-bone marrow transplantation.
AB  - This study examined the prevalence of vitamin K deficiency in children pre-bone
      marrow transplantation (BMT). Vitamin K status was measured by the PIVKA-II assay
      and prothrombin times. Blood samples were obtained before vitamin-containing TPN
      was infused. Results indicated that eight of 26 patients (31%) were vitamin K
      deficient; four cases were attributed to drug antagonism (phenytoin) and four
      were due to inadequate vitamin K intake, synthesis or malabsorption. Only one
      patient had a prolonged prothrombin time. Prothrombin time, in our study, is
      shown to be an ineffective screening tool to determine vitamin K status. All
      patients receiving phenytoin and chemotherapy are at increased risk of vitamin K
      deficiency.

PMID- 16284613
TI  - Once daily ganciclovir as initial pre-emptive therapy delayed until threshold CMV
      load > or =10000 copies/ml: a safe and effective strategy for allogeneic stem
      cell transplant patients.
AB  - Quantitative polymerase chain reaction (QPCR) for cytomegalovirus (CMV) is
      emerging as the preferred screening method for detection of CMV viremia in
      patients following allogeneic bone marrow and peripheral blood stem cell
      transplant. However, there are currently no universally accepted QPCR treatment
      thresholds at which to start pre-emptive therapy. We report here results of a pre
      emptive therapy strategy using ganciclovir (GCV) 5 mg/kg initiated once daily
      (ODG) delayed till a threshold CMV load of > or =10 000 copies/ml whole blood in
      clinically stable patients. Sixty-nine at risk patients underwent allogeneic stem
      cell transplant. 48/69 (70%) patients had an initial episode of CMV viremia. 5/48
      (10%) cleared viremia without requiring treatment. 28/43 (65%) patients requiring
      treatment initiated treatment with ODG. 17/28 (61%) patients successfully cleared
      CMV viremia on ODG, 10/28 (36%) patients required dose escalation to twice daily
      GCV for increasing viral loads. There were two cases of CMV disease (colitis) and
      no deaths due to CMV disease in patients initiating treatment with ODG. We
      conclude delaying pre-emptive therapy with ODG until whole blood QPCR> or =10 000
      copies/ml is a safe and effective strategy for CMV viremia after allogeneic stem
      cell transplant in clinically stable patients.

PMID- 16284614
TI  - Efficacy of neodymium:YAG laser therapy for gastric antral vascular ectasia
      (GAVE) following hematopoietic cell transplant.
AB  - We determined the incidence of severe bleeding from gastric antral vascular
      ectasia (GAVE) after myeloablative hematopoietic cell transplant and the outcomes
      after treatment with endoscopic neodymium:YAG laser photocoagulation. From 1992
      to 2005, the incidence of severe bleeding from GAVE was 6/4491 (0.13%). All
      patients had received oral busulfan and four had sinusoidal obstruction syndrome.
      Gastrointestinal bleeding began a median of 53 days after transplant (range 15
      2952). After GAVE was diagnosed by endoscopic and histologic findings, a median
      of three (range 2-7) sessions of laser therapy were required to control the
      bleeding with a median of 2737 J (range 1117-6160 J) per session. A median of 16
      units (range 4-44) had been transfused prior to laser therapy and a median of
      four additional units (range 0-113) were transfused until bleeding was
      controlled. All patients were followed for at least 70 days after the last laser
      therapy session, with no further episodes of bleeding. Complications were mild
      and included abdominal pain and asymptomatic ulceration; however, one patient
      required gastrectomy due to gastric necrosis following transarterial
      embolizations. In summary, severe bleeding from GAVE is rare following
      hematopoietic cell transplant. Treatment with endoscopic therapy using the Nd:YAG
      laser is safe and effective.

PMID- 16284615
TI  - Unrelated donor or partially matched related donor peripheral stem cell
      transplant with CD34+ selection and CD3+ addback for pediatric patients with
      leukemias.
AB  - Unmodified peripheral stem cell transplants are associated with an increased risk
      of extensive chronic GVHD. T depletion may reduce this risk, but the risk of
      graft failure or relapse may increase. To decrease the risks of both extensive
      chronic GVHD and graft failure, we added back a defined dose of CD3+ cells to
      CD34+ selected PSCs. Twenty-four patients were evaluable for outcome analysis.
      Donors were unrelated (23) or related (1). Conditioning was thiotepa,
      cyclophosphamide, and total body irradiation. Cyclosporine was used post
      transplant. Following CD34+ selection, a total of 5 x 10(5)/kg CD3+ cells were
      infused. Donors were matched for 12 patients. The median CD34+ dose infused was
      7.1 x 10(6)/kg. Engraftment occurred in all patients at a median of 14 days (10
      19). Twelve patients are alive in remission 15-34 months (median, 25) post PSCT.
      GVHD occurred in 17 patients, but was >grade II in only 2. Chronic GVHD occurred
      in 61.5% of evaluable patients, but was limited to skin and perioral cavity. Two
      patients relapsed, and 10 patients died of non-relapse causes. This study
      demonstrates that PSCT with CD34+ selection and a defined dose of CD3+ results in
      prompt engraftment and may limit development of extensive chronic GVHD.

PMID- 16284616
TI  - Is there a role for high-dose methylprednisolone in the treatment of hepatic
      regimen-related toxicity?

PMID- 16284617
TI  - Direct observation of base-pair stepping by RNA polymerase.
AB  - During transcription, RNA polymerase (RNAP) moves processively along a DNA
      template, creating a complementary RNA. Here we present the development of an
      ultra-stable optical trapping system with angstrom-level resolution, which we
      used to monitor transcriptional elongation by single molecules of Escherichia
      coli RNAP. Records showed discrete steps averaging 3.7 +/- 0.6 A, a distance
      equivalent to the mean rise per base found in B-DNA. By combining our results
      with quantitative gel analysis, we conclude that RNAP advances along DNA by a
      single base pair per nucleotide addition to the nascent RNA. We also determined
      the force-velocity relationship for transcription at both saturating and sub
      saturating nucleotide concentrations; fits to these data returned a
      characteristic distance parameter equivalent to one base pair. Global fits were
      inconsistent with a model for movement incorporating a power stroke tightly
      coupled to pyrophosphate release, but consistent with a brownian ratchet model
      incorporating a secondary NTP binding site.

PMID- 16284618
TI  - Concerted action of poly(A) nucleases and decapping enzyme in mammalian mRNA
      turnover.
AB  - In mammalian cells, the enzymatic pathways involved in cytoplasmic mRNA decay are
      incompletely defined. In this study, we have used two approaches to disrupt
      activities of deadenylating and/or decapping enzymes to monitor effects on mRNA
      decay kinetics and trap decay intermediates. Our results show that deadenylation
      is the key first step that triggers decay of both wild-type stable and nonsense
      codon-containing unstable beta-globin mRNAs in mouse NIH3T3 fibroblasts. PAN2 and
      CCR4 are the major poly(A) nucleases active in cytoplasmic deadenylation that
      have biphasic kinetics, with PAN2 initiating deadenylation followed by CCR4
      mediated poly(A) shortening. DCP2-mediated decapping takes place after
      deadenylation and may serve as a backup mechanism for triggering mRNA decay when
      initial deadenylation by PAN2 is compromised. Our findings reveal a functional
      link between deadenylation and decapping and help to define in vivo pathways for
      mammalian cytoplasmic mRNA decay.

PMID- 16284619
TI  - Conformational transition of initiation factor 2 from the GTP- to GDP-bound state
      visualized on the ribosome.
AB  - Initiation of protein synthesis is a universally conserved event that requires
      initiation factors IF1, IF2 and IF3 in prokaryotes. IF2 is a GTPase essential for
      binding initiator transfer RNA to the 30S ribosomal subunit and recruiting the
      50S subunit into the 70S initiation complex. We present two cryo-EM structures of
      the assembled 70S initiation complex comprising mRNA, fMet-tRNA(fMet) and IF2
      with either a non-hydrolyzable GTP analog or GDP. Transition from the GTP-bound
      to the GDP-bound state involves substantial conformational changes of IF2 and of
      the entire ribosome. In the GTP analog-bound state, IF2 interacts mostly with the
      30S subunit and extends to the initiator tRNA in the peptidyl (P) site, whereas
      in the GDP-bound state IF2 steps back and adopts a 'ready-to-leave' conformation.
      Our data also provide insights into the molecular mechanism guiding release of
      IF1 and IF3.

PMID- 16284620
TI  - Morphology-tuned wurtzite-type ZnS nanobelts.
AB  - Nanometre-sized inorganic dots, wires and belts have a wide range of electrical
      and optical properties, and variable mechanical stability and phase-transition
      mechanisms that show a sensitive dependency on size, shape and structure. The
      optical properties of the semiconductor ZnS in wurtzite structures are
      considerably enhanced, but the lack of structural stability limits technological
      applications. Here, we demonstrate that morphology-tuned wurtzite ZnS nanobelts
      show a particular low-energy surface structure dominated by the +/-[210] surface
      facets. Experiments and calculations show that the morphology of ZnS nanobelts
      leads to a very high mechanical stability to approximately 6.8 GPa, and also
      results in an explosive mechanism for the wurtzite-to-sphalerite phase
      transformation together with in situ fracture of the nanobelts. ZnS wurtzite
      nanobelts provide a model that is useful not only for understanding the
      morphology-tuned stability and transformation mechanism, but also for improving
      synthesis of metastable nanobelts with quantum effects for electronic and optical
      devices.

PMID- 16284621
TI  - Spontaneous formation of nanoparticle stripe patterns through dewetting.
AB  - Significant advancement has been made in nanoparticle research, with synthetic
      techniques extending over a wide range of materials with good control over
      particle size and shape. A grand challenge is assembling and positioning the
      nanoparticles in desired locations to construct complex, higher-order functional
      structures. Controlled positioning of nanoparticles has been achieved in pre
      defined templates fabricated by top-down approaches. A self-assembly method,
      however, is highly desirable because of its simplicity and compatibility with
      heterogeneous integration processes. Here we report on the spontaneous formation
      of ordered gold and silver nanoparticle stripe patterns on dewetting a dilute
      film of polymer-coated nanoparticles floating on a water surface. Well-aligned
      stripe patterns with tunable orientation, thickness and periodicity at the
      micrometre scale were obtained by transferring nanoparticles from a floating film
      onto a substrate in a dip-coating fashion. This facile technique opens up a new
      avenue for lithography-free patterning of nanoparticle arrays for various
      applications including, for example, multiplexed surface-enhanced Raman
      substrates and templated fabrication of higher-order nanostructures.

PMID- 16284622
TI  - Disruption of GW bodies impairs mammalian RNA interference.
AB  - The GW182 RNA-binding protein was initially shown to associate with a specific
      subset of mRNAs and to reside within discrete cytoplasmic foci named GW bodies
      (GWBs). GWBs are enriched in proteins that are involved in mRNA degradation.
      Recent reports have shown that exogenously introduced human Argonaute-2 (Ago2) is
      also enriched in GWBs, indicating that RNA interference function may be somehow
      linked to these structures. In this report, we demonstrate that endogenous Ago2
      and transfected small interfering RNAs (siRNAs) are also present within these
      same cytoplasmic bodies and that the GW182 protein interacts with Ago2.
      Disruption of these cytoplasmic foci in HeLa cells interferes with the silencing
      capability of a siRNA that is specific to lamin-A/C. Our data support a model in
      which GW182 and/or the microenvironment of the cytoplasmic GWBs contribute to the
      RNA-induced silencing complex and to RNA silencing.

PMID- 16284623
TI  - A role for the P-body component GW182 in microRNA function.
AB  - In animals, the majority of microRNAs regulate gene expression through the RNA
      interference (RNAi) machinery without inducing small-interfering RNA (siRNA)
      directed mRNA cleavage. Thus, the mechanisms by which microRNAs repress their
      targets have remained elusive. Recently, Argonaute proteins, which are key RNAi
      effector components, and their target mRNAs were shown to localize to cytoplasmic
      foci known as P-bodies or GW-bodies. Here, we show that the Argonaute proteins
      physically interact with a key P-/GW-body subunit, GW182. Silencing of GW182
      delocalizes resident P-/GW-body proteins and impairs the silencing of microRNA
      reporters. Moreover, mutations that prevent Argonaute proteins from localizing in
      P-/GW-bodies prevent translational repression of mRNAs even when Argonaute is
      tethered to its target in a siRNA-independent fashion. Thus, our results support
      a functional link between cytoplasmic P-bodies and the ability of a microRNA to
      repress expression of a target mRNA.

PMID- 16284624
TI  - Evidence for a protein transported through the secretory pathway en route to the
      higher plant chloroplast.
AB  - In contrast to animal and fungal cells, green plant cells contain one or multiple
      chloroplasts, the organelle(s) in which photosynthetic reactions take place.
      Chloroplasts are believed to have originated from an endosymbiotic event and
      contain DNA that codes for some of their proteins. Most chloroplast proteins are
      encoded by the nuclear genome and imported with the help of sorting signals that
      are intrinsic parts of the polypeptides. Here, we show that a chloroplast-located
      protein in higher plants takes an alternative route through the secretory
      pathway, and becomes N-glycosylated before entering the chloroplast.

PMID- 16284625
TI  - Regulation of Notch signalling by non-visual beta-arrestin.
AB  - Signalling activity of the Notch receptor, which plays a fundamental role in
      metazoan cell fate determination, is controlled at multiple levels. We uncovered
      a Notch signal-controlling mechanism that depends on the ability of the non
      visual beta-arrestin, Kurtz (Krz), to influence the degradation and,
      consequently, the function of the Notch receptor. We identified Krz as a binding
      partner of a known Notch-pathway modulator, Deltex (Dx), and demonstrated the
      existence of a trimeric Notch-Dx-Krz protein complex. This complex mediates the
      degradation of the Notch receptor through a ubiquitination-dependent pathway. Our
      results establish a novel mode of regulation of Notch signalling and define a new
      function for non-visual beta-arrestins.

PMID- 16284626
TI  - 4-methyl benzylamine stimulates food consumption and counteracts the hypophagic
      effects of amphetamine acting on brain Shaker-like Kv1.1 channels.
AB  - 1.--4-methyl benzylamine (4-MBZ; 28 microg, 231 nmol) elicits a hyperphagic
      response in starved mice in contrast to the hypophagia induced by the parent
      compound benzylamine (BZ; 33 microg, 231 nmol) or by amphetamine (AMPH, 2 mug).
      2.--In mice starved for only 4 h, and therefore with little stimulation to eat,
      the maximal increase in food consumption induced by intracerebroventricular
      (i.c.v.)-injected 4-MBZ was 190% over that of the controls (ED(50) 8.3+/-2.7
      microg mouse(-1); 68+/-22 nmol mouse(-1)), whereas after i.p. administration,
      these values were 160% and approximately 129 mg kg(-1), respectively. 3.--The
      hyperphagic effect of 4-MBZ was reduced by more than 60% in mice pretreated with
      antisense oligodeoxyribonucleotide (aODN(1)) previously found to selectively
      inhibit (over 50%) the expression of Shaker-like Kv1.1 channels. 4.--In mice
      highly stimulated to eat after 12-h fasting, 4-MBZ (28 microg) significantly
      reduced (to about 70%) the hypophagic response by AMPH (2 microg) or BZ (33
      microg). Conversely, these two compounds reduced (respectively, by 69 and 44%)
      the hyperphagic response of 4-MBZ in 4-h fasting mice. 5.--4-MBZ (28 microg) also
      reduced the hypermotility and the stimulation of inspection activity elicited by
      AMPH in mice and the release of DA stimulated by AMPH (2 microg) from the nucleus
      accumbens of rats. We hypothesize that 4-MBZ elicits hyperphagic effects probably
      by opening Shaker-like Kv1.1 subtypes in the brain, whereas AMPH and BZ are
      hypophagic by blocking these channels.

PMID- 16284627
TI  - Transcriptional activation of p21 by Tranilast is mediated via transforming
      growth factor beta signal pathway.
AB  - Tranilast, an antiallergic medication, is a very promising inhibitor of
      restenosis after balloon angioplasty. Tranilast can prevent the proliferation and
      migration of smooth muscle cells by activating the gene expression of p21, a
      strong cyclin/cyclin-dependent kinase (CDK) inhibitor, and by arresting cell
      growth at the G0/G1 phase. The signaling pathway of Tranilast in regulating p21
      is to our best interest and is elucidated in the present study. The major
      emphasis was weighted on exploring the regulatory effects of Tranilast on
      promoter activity of p21. By serial deletion analysis, the sequence between -74
      and -83 bp of the p21 promoter, previously identified as the transforming growth
      factor-beta (TGF-beta)-response element, was found sufficient, where as most of
      the promoter region 5' to -111 bp was found unnecessary for the transcriptional
      activation of p21 by both TGF-beta1 and Tranilast. Tranilast was also found to
      induce phosphorylation of Smad2 (a cytoplasmic signaling molecule essential for
      mediating TGF-beta signal transduction). Transfection of DeltakTbetaRII, a
      truncated form of TGF-beta type II receptor known to exert a dominant-negative
      effect on TGF-beta signaling, was found to suppress the signaling of both
      Tranilast and TGF-beta1 to a similar extent. These results suggested that
      induction of p21 by Tranilast might be closely related to TGF-beta signal
      transduction pathway.

PMID- 16284629
TI  - Characterization of the Mas-related gene family: structural and functional
      conservation of human and rhesus MrgX receptors.
AB  - Recently, a large family of G-protein-coupled receptors called Mas-related genes
      (Mrgs), which is selectively expressed in small-diameter sensory neurons of
      dorsal root ganglia, was described. A subgroup of human Mrg receptors (MrgX1-X4)
      is not found in rodents and this has hampered efforts to define the physiological
      roles of these receptors. MrgX receptors were cloned from rhesus monkey and
      functionally characterized alongside their human orthologs. Most of the human and
      rhesus MrgX receptors displayed high constitutive activity in a cellular
      proliferation assay. Proliferative responses mediated by human or rhesus MrgX1,
      or rhesus MrgX2 were partially blocked by pertussis toxin (PTX). Proliferative
      responses mediated by rhesus MrgX3 and both human and rhesus MrgX4 were PTX
      insensitive. These results indicate that human and rhesus MrgX1 and MrgX2
      receptors activate both Gq- and Gi-regulated pathways, while MrgX3 and MrgX4
      receptors primarily stimulate Gq-regulated pathways. Peptides known to activate
      human MrgX1 and MrgX2 receptors activated the corresponding rhesus receptors in
      cellular proliferation assays, Ca(2+)-mobilization assays, and GTP-gammaS-binding
      assays. Cortistatin-14 was selective for human and rhesus MrgX2 receptors over
      human and rhesus MrgX1 receptors. BAM22 and related peptides strongly activated
      human MrgX1 receptors, but weakly activated rhesus MrgX1, human MrgX2, and rhesus
      MrgX2 receptors. These data suggest that the rhesus monkey may be a suitable
      animal model for exploring the physiological roles of the MrgX receptors.

PMID- 16284628
TI  - Piracetam improves mitochondrial dysfunction following oxidative stress.
AB  - 1.--Mitochondrial dysfunction including decrease of mitochondrial membrane
      potential and reduced ATP production represents a common final pathway of many
      conditions associated with oxidative stress, for example, hypoxia, hypoglycemia,
      and aging. 2.--Since the cognition-improving effects of the standard nootropic
      piracetam are usually more pronounced under such pathological conditions and
      young healthy animals usually benefit little by piracetam, the effect of
      piracetam on mitochondrial dysfunction following oxidative stress was
      investigated using PC12 cells and dissociated brain cells of animals treated with
      piracetam. 3.--Piracetam treatment at concentrations between 100 and 1000 microM
      improved mitochondrial membrane potential and ATP production of PC12 cells
      following oxidative stress induced by sodium nitroprusside (SNP) and serum
      deprivation. Under conditions of mild serum deprivation, piracetam (500 microM)
      induced a nearly complete recovery of mitochondrial membrane potential and ATP
      levels. Piracetam also reduced caspase 9 activity after SNP treatment. 4.-
      Piracetam treatment (100-500 mg kg(-1) daily) of mice was also associated with
      improved mitochondrial function in dissociated brain cells. Significant
      improvement was mainly seen in aged animals and only less in young animals.
      Moreover, the same treatment reduced antioxidant enzyme activities (superoxide
      dismutase, glutathione peroxidase, and glutathione reductase) in aged mouse brain
      only, which are elevated as an adaptive response to the increased oxidative
      stress with aging. 5.--In conclusion, therapeutically relevant in vitro and in
      vivo concentrations of piracetam are able to improve mitochondrial dysfunction
      associated with oxidative stress and/or aging. Mitochondrial stabilization and
      protection might be an important mechanism to explain many of piracetam's
      beneficial effects in elderly patients.

PMID- 16284630
TI  - Antiviral prodrugs - the development of successful prodrug strategies for
      antiviral chemotherapy.
AB  - Following the discovery of the first effective antiviral compound (idoxuridine)
      in 1959, nucleoside analogues, especially acyclovir (ACV) for the treatment of
      herpesvirus infections, have dominated antiviral therapy for several decades.
      However, ACV and similar acyclic nucleosides suffer from low aqueous solubility
      and low bioavailability following oral administration. Derivatives of acyclic
      nucleosides, typically esters, were developed to overcome this problem and
      valaciclovir, the valine ester of ACV, was among the first of a new series of
      compounds that were readily metabolized upon oral administration to produce the
      antiviral nucleoside in vivo, thus increasing the bioavailility by several fold.
      Concurrently, famciclovir was developed as an oral formulation of penciclovir.
      These antiviral 'prodrugs' thus established a principle that has led to many
      successful drugs including both nucleoside and nucleotide analogues for the
      control of several virus infections, notably those caused by herpes-, retro- and
      hepatitisviruses. This review will chart the origins and development of the most
      important of the antiviral prodrugs to date.

PMID- 16284632
TI  - Question everything: the value of integrating research into an athletic training
      education.

PMID- 16284631
TI  - New potent and selective inhibitors of anandamide reuptake with antispastic
      activity in a mouse model of multiple sclerosis.
AB  - We previously reported that the compound O-2093 is a selective inhibitor of the
      reuptake of the endocannabinoid anandamide (AEA). We have now re-examined the
      activity of O-2093 in vivo and synthesized four structural analogs (O-2247, O
      2248, O-3246, and O-3262), whose activity was assessed in: (a) binding assays
      carried out with membranes from cells overexpressing the human CB(1) and CB(2)
      receptors; (b) assays of transient receptor potential of the vanilloid type-1
      (TRPV1) channel functional activity (measurement of [Ca(2+)](i)); (c) [(14)C]AEA
      cellular uptake and hydrolysis assays in rat basophilic leukaemia (RBL-2H3)
      cells; (d) the mouse 'tetrad' tests (analgesia on a hot plate, immobility on a
      'ring', rectal hypothermia and hypolocomotion in an open field); and (e) the limb
      spasticity test in chronic relapsing experimental allergic encephalomyelitis
      (CREAE) mice, a model of multiple sclerosis (MS). O-2093, either synthesized by
      us or commercially available, was inactive in the 'tetrad' up to a 20 mg kg(-1)
      dose (i.v.). Like O-2093, the other four compounds exhibited low affinity in
      CB(1) (K(i) from 1.3 to >10 microM) and CB(2) binding assays (1.3<K(i)< 8
      microM), low potency and efficacy in a TRPV1 functional assay (EC(50)>10 microM),
      very low potency as fatty acid amide hydrolase (FAAH) inhibitors (IC(50)>25
      microM) and were inactive in the 'tetrad' up to a 30 mg kg(-1) dose (i.v.). While
      O-2247 and O-2248 were poor inhibitors of [(14)C]AEA cellular uptake (IC(50)>40
      microM), O-3246 and O-3262 were quite potent in this assay. O-3246, which
      exhibits only a very subtle structural difference with O-2093, is the most potent
      inhibitor of AEA uptake reported in vitro under our experimental conditions
      (IC(50)=1.4 microM) and is 12-fold more potent than O-2093. When injected
      intravenously O-3246 and O-3262, again like O-2093 and unlike O-2247 and O-2248,
      significantly inhibited limb spasticity in mice with CREAE. These data confirm
      the potential utility of selective AEA uptake inhibitors as anti-spasticity drugs
      in MS and, given the very subtle chemical differences between potent and weak
      inhibitors of uptake, support further the existence of a specific mechanism for
      this process.

PMID- 16284633
TI  - Is neuropsychological testing useful in the management of sport-related
      concussion?
AB  - OBJECTIVE: Neuropsychological (NP) testing has been used for several years as a
      way of detecting the effects of sport-related concussion in order to aid in
      return-to-play determinations. In addition to standard pencil-and-paper tests,
      computerized NP tests are being commercially marketed for this purpose to
      professional, collegiate, high school, and elementary school programs. However, a
      number of important questions regarding the clinical validity and utility of
      these tests remain unanswered, and these questions present serious challenges to
      the applicability of NP testing for the management of sport-related concussion.
      Our purpose is to outline the criteria that should be met in order to establish
      the utility of NP instruments as a tool in the management of sport-related
      concussion and to review the degree to which existing tests have met these
      criteria. DATA SOURCES: A comprehensive literature review of MEDLINE and PsychLit
      from 1990 to 2004, including all prospective, controlled studies of NP testing in
      sport-related concussion. DATA SYNTHESIS: The effects of concussion on NP test
      performance are so subtle even during the acute phase of injury (1-3 days
      postinjury) that they often fail to reach statistical significance in group
      studies. Thus, this method may lack utility in individual decision making because
      of a lack of sensitivity. In addition, most of these tests fail to meet other
      psychometric criteria (eg, adequate reliability) necessary for this purpose.
      Finally, it is unclear that NP testing can detect impairment in players once
      concussion-related symptoms (eg, headache) have resolved. Because no current
      guideline for the management of sport-related concussion allows a symptomatic
      player to return to sport, the incremental utility of NP testing remains
      questionable. CONCLUSIONS/RECOMMENDATIONS: Despite the theoretic rationale for
      the use of NP testing in the management of sport-related concussion, no NP tests
      have met the necessary criteria to support a clinical application at this time.
      Additional research is necessary to establish the utility of these tests before
      they can be considered part of a routine standard of care, and concussion
      recovery should be monitored via the standard clinical examination and subjective
      symptom checklists until NP testing or other methods are proven effective for
      this purpose.

PMID- 16284634
TI  - Cervical spine functional anatomy and the biomechanics of injury due to
      compressive loading.
AB  - OBJECTIVE: To provide a foundation of knowledge concerning the functional
      anatomy, kinematic response, and mechanisms involved in axial-compression
      cervical spine injury as they relate to sport injury. DATA SOURCES: We conducted
      literature searches through the Index Medicus, SPORT Discus, and PubMed databases
      and the Library of Congress from 1975-2003 using the key phrases cervical spine
      injury, biomechanics of cervical spine, football spinal injuries, kinematics of
      the cervical spine, and axial load. DATA SYNTHESIS: Research on normal kinematics
      and minor and major injury mechanisms to the cervical spine reveals the complex
      nature of movement in this segment. The movement into a single plane is not the
      product of equal and summative movement between and among all cervical vertebrae.
      Instead, individual vertebrae may experience a reversal of motion while traveling
      through a single plane of movement. Furthermore, vertebral movement in 1 plane
      often requires contributed movement in 1 or 2 other planes. Injury mechanisms are
      even more complex. The reaction of the cervical spine to an axial-load impact has
      been investigated using cadaver specimens and demonstrates a buckling effect.
      Impact location and head orientation affect the degree and level of resultant
      injury. CONCLUSIONS/RECOMMENDATIONS: As with any joint of the body, our
      understanding of the mechanisms of cervical spine injury will ultimately serve to
      reduce their occurrence and increase the likelihood of recognition and immediate
      care. However, the cervical spine is unique in its normal kinematics compared
      with joints of the extremities. Injury biomechanics in the cervical spine are
      complex, and much can still be learned about mechanisms of the cervical spine
      injury specific to sports.

PMID- 16284635
TI  - A comparison of head movement during back boarding by motorized spine-board and
      log-roll techniques.
AB  - CONTEXT: In a patient with a potential cervical spine injury, minimizing or
      eliminating movement at the head and neck during stabilization and transport is
      paramount because movement can exacerbate the condition. Any equipment or
      technique creating less movement will allow for a more effective and safe
      stabilization of an injured patient, reducing the likelihood of movement and
      potential secondary injury. OBJECTIVE: To compare the amount of head movement
      created during the log-roll and motorized spine-board (MSB) stabilization
      techniques. DESIGN: A 2-condition, repeated-measures design. SETTING: Laboratory.
      PATIENTS OR OTHER PARTICIPANTS: Thirteen certified athletic trainers, emergency
      first responders, and emergency medical technicians (6 men, 7 women).
      INTERVENTION(S): Subjects rotated through 4 positions for the log roll and 2
      positions for the MSB. Each subject performed 3 trials while maintaining manual,
      inline stabilization of the model's head for each condition. MAIN OUTCOME
      MEASURE(S): Three-dimensional head movement was measured and expressed as degrees
      of motion. RESULTS: The log roll created significantly more motion in the frontal
      and transverse planes compared with the MSB (P = .001 for both measures). No
      significant difference was noted for sagittal-plane motion (P = .028).
      CONCLUSIONS: The MSB created less movement at the head than did the log roll in 2
      planes of motion and created slightly more motion in 1 plane, although this
      difference was not significant. The MSB may provide emergency responders with an
      appropriate alternative method for stabilizing and transporting a supine injured
      athlete without requiring a log roll.

PMID- 16284636
TI  - Football face-mask removal with a cordless screwdriver on helmets used for at
      least one season of play.
AB  - CONTEXT: The Inter-Association Task Force for the Appropriate Care of the Spine
      Injured Athlete recommends leaving a football player's helmet in place and
      removing the face mask from the helmet "as quickly as possible and with as little
      movement of the head and neck as possible." Although 2 groups have studied face
      mask removal from new equipment, to our knowledge no researchers have
      investigated equipment that has been previously used. A full season of play may
      have a significant effect on football equipment and its associated hardware.
      Countless impacts, weather, playing surfaces, sweat, and other unforeseen or
      unknown variables might make the face-mask removal process more difficult on
      equipment that has been used. OBJECTIVE: To determine the percentage of face
      masks that we could unscrew, with a cordless screwdriver, from football helmets
      used for a full season. DESIGN: Cross-sectional. SETTING: Three New England high
      schools. PATIENTS OR OTHER PARTICIPANTS: All football helmets used at 3 local
      high schools were tested (n = 222, mean games, 9.7 +/- 1.2; mean practice weeks,
      13.7 +/- 1.2). INTERVENTION(S): Each helmet was secured to a board, and a
      cordless screwdriver was used to attempt to remove all 4 screws attaching the
      face mask to the helmet. MAIN OUTCOME MEASURE(S): Variables included overall
      success or failure, time required for face-mask removal, and success by screw
      location. Data were analyzed with chi2, analysis of variance, and Tamhane post
      hoc tests. RESULTS: Overall, 832 (94%) of 885 screws were unscrewed, and 183
      (82.4%) of 222 face masks were removed. Mean removal time was 26.9 +/- 5.83
      seconds. Face-mask removal success was significantly different between school 1
      (24 [52.2%] of 46) and schools 2 (84 [91.3%] of 92) and 3 (75 [89.3%] of 84;
      F(2,219) = 24.608; P < .001). The removal success rate was significantly higher
      at top screws (98%) than at screws adjacent to ear holes (90%) (P < .001).
      CONCLUSIONS: Based on our results and previous findings that demonstrated quicker
      access time and reduced head movement associated with the use of the screwdriver
      compared with cutting tools, the former may be a good tool for face-mask removal.
      However, an appropriate cutting tool must be immediately available should the
      screwdriver fail. Helmet hardware adjacent to ear holes was more vulnerable to
      failure, perhaps because it is protected by less padding than the top hardware.
      Possible causes of the higher failure rate at school 1 are the use of hardware
      materials subject to rust and corrosion and differences in helmet brand; these
      areas warrant future research and rules consideration.

PMID- 16284637
TI  - Effects of massage on delayed-onset muscle soreness, swelling, and recovery of
      muscle function.
AB  - CONTEXT: Delayed-onset muscle soreness (DOMS) describes muscle pain and
      tenderness that typically develop several hours postexercise and consist of
      predominantly eccentric muscle actions, especially if the exercise is unfamiliar.
      Although DOMS is likely a symptom of eccentric-exercise-induced muscle damage, it
      does not necessarily reflect muscle damage. Some prophylactic or therapeutic
      modalities may be effective only for alleviating DOMS, whereas others may enhance
      recovery of muscle function without affecting DOMS. OBJECTIVE: To test the
      hypothesis that massage applied after eccentric exercise would effectively
      alleviate DOMS without affecting muscle function. DESIGN: We used an arm-to-arm
      comparison model with 2 independent variables (control and massage) and 6
      dependent variables (maximal isometric and isokinetic voluntary strength, range
      of motion, upper arm circumference, plasma creatine kinase activity, and muscle
      soreness). A 2-way repeated-measures analysis of variance and paired t tests were
      used to examine differences in changes of the dependent variable over time
      (before, immediately and 30 minutes after exercise, and 1, 2, 3, 4, 7, 10, and 14
      days postexercise) between control and massage conditions. SETTING: University
      laboratory. PATIENTS OR OTHER PARTICIPANTS: Ten healthy subjects (5 men and 5
      women) with no history of upper arm injury and no experience in resistance
      training. INTERVENTION(S): Subjects performed 10 sets of 6 maximal isokinetic (90
      degrees x s(-1)) eccentric actions of the elbow flexors with each arm on a
      dynamometer, separated by 2 weeks. One arm received 10 minutes of massage 3 hours
      after eccentric exercise; the contralateral arm received no treatment. MAIN
      OUTCOME MEASURE(S): Maximal voluntary isometric and isokinetic elbow flexor
      strength, range of motion, upper arm circumference, plasma creatine kinase
      activity, and muscle soreness. RESULTS: Delayed-onset muscle soreness was
      significantly less for the massage condition for peak soreness in extending the
      elbow joint and palpating the brachioradialis muscle (P < .05). Soreness while
      flexing the elbow joint (P = .07) and palpating the brachialis muscle (P = .06)
      was also less with massage. Massage treatment had significant effects on plasma
      creatine kinase activity, with a significantly lower peak value at 4 days
      postexercise (P < .05), and upper arm circumference, with a significantly smaller
      increase than the control at 3 and 4 days postexercise (P < .05). However, no
      significant effects of massage on recovery of muscle strength and ROM were
      evident. CONCLUSIONS: Massage was effective in alleviating DOMS by approximately
      30% and reducing swelling, but it had no effects on muscle function.

PMID- 16284638
TI  - Effects of sport massage on limb girth and discomfort associated with eccentric
      exercise.
AB  - CONTEXT: Sport massage is often used to help prepare for exercise, expedite
      recovery from muscle soreness, and enhance athletic performance. However, the
      effect of sport massage on recovery from delayed-onset muscle soreness is
      unknown. OBJECTIVE: To determine the effect of a short sport massage treatment on
      intramuscular swelling and pain in response to eccentric exercise. DESIGN: We
      used a 2 x 8 (treatment x time) repeated-measures design to compare triceps surae
      muscle girth and pain ratings over the 72 hours after eccentric exercise.
      SETTING: University research laboratory. PATIENTS OR OTHER PARTICIPANTS: Nineteen
      healthy, college-aged subjects. INTERVENTION(S): Delayed-onset muscle soreness
      was induced with several sets of eccentric triceps surae contractions at 90% of
      the estimated concentric, 1-repetition maximum weight. Subjects returned on 3
      consecutive days after eccentric exercise with a cycle ergometer for active rest
      treatments. In addition, 1 leg received the sport massage. MAIN OUTCOME
      MEASURE(S): Girth measurements were taken at 5.08 cm (2 in), 10.16 cm (4 in),
      15.24 cm (6 in), and 20.32 cm (8 in) below the knee joint line, and pain was
      assessed with a visual analog scale before and after all 4 sessions. RESULTS: No
      interaction was noted between treatment and time for any girth or pain
      measurements, and no main effect was seen for treatment. CONCLUSIONS: Sport
      massage did not reduce girth or pain in the lower leg after eccentric exercise
      within 72 hours.

PMID- 16284639
TI  - Appraising clinical studies: a commentary on the Zainuddin et al and Hart et al
      studies.

PMID- 16284641
TI  - Effects of partial immobilization after eccentric exercise on recovery from
      muscle damage.
AB  - CONTEXT: Short-term strict immobilization of the arm using a cast enhances
      recovery of muscle function after eccentric exercise. OBJECTIVE: To determine if
      placing one arm in a sling ("light" immobilization) for 4 days after eccentric
      exercise of the elbow flexor muscles would reduce muscle soreness and enhance
      recovery compared with the exercised but not immobilized contralateral arm.
      DESIGN: Subjects performed 10 sets of 6 maximal isokinetic (90 degrees x s(-1))
      eccentric actions of the elbow flexors of each arm on a Cybex dynamometer,
      separated by 2 weeks. SETTING: University laboratory. PATIENTS OR OTHER
      PARTICIPANTS: Ten healthy subjects (5 men and 5 women) with no history of upper
      arm injury or resistance training. INTERVENTION(S): One randomly assigned arm was
      placed in a sling for 4 days after the 30-minute postexercise measurement to
      secure the elbow joint at 90 degrees ; the contralateral arm received no
      treatment. The subject removed the sling when showering and sleeping and during
      postexercise measurements. MAIN OUTCOME MEASURE(S): We used an activity monitor
      to record upper arm activity before and after immobilization. We also compared
      changes in maximal isometric and isokinetic voluntary strength, range of motion,
      upper arm circumference, plasma creatine kinase activity, and muscle soreness
      during 7 days postexercise between arms with a 2-way, repeated-measures analysis
      of variance. RESULTS: Eccentric exercise resulted in large losses in both
      isometric and isokinetic maximal voluntary contraction forces (approximately
      40%), reduced range of motion (approximately 20%), increased arm circumference
      (approximately 10 mm), elevated plasma creatine kinase activity (approximately
      2000 IU x L(-1)), and development of delayed-onset muscle soreness. No
      significant differences were noted between conditions for any measure except
      upper arm circumference, which increased significantly less for the
      immobilization than the control arm at 7 days postexercise (P < .05).
      CONCLUSIONS: Light immobilization had no effect on enhancing recovery of muscle
      function and delayed-onset muscle soreness after eccentric-exercise-induced
      muscle damage.

PMID- 16284640
TI  - Effects of 2 ankle fatigue models on the duration of postural stability
      dysfunction.
AB  - CONTEXT: Muscle fatigue is generally categorized in 2 ways: that caused by
      peripheral weakness (peripheral fatigue) and that caused by a progressive failure
      of voluntary neural drive (central fatigue). Numerous variables have been studied
      in conjunction with fatigue protocols, including postural stability, maximum
      voluntary contraction force, and reaction time. When torque recordings fall below
      50% of a maximum voluntary contraction, the muscle is described as fatigued, but
      whether this value is a good indicator of fatigue has not been studied.
      OBJECTIVE: To compare the effects of 2 ankle musculature fatigue protocols (30%
      and 50%) on the duration of postural stability dysfunction. DESIGN: To assess
      differences between the 30% and 50% fatigue protocols, we calculated a 1 between
      groups factor (subjects) and 2 within-groups factors (fatigue, test) analysis of
      variance. SETTING: E.J. Nutter Athletic Training Facility. PATIENTS OR OTHER
      PARTICIPANTS: Twenty subjects (10 men, 10 women; age = 21.15 +/- 2.23 years;
      height = 172.97 +/- 9.86 cm; mass = 70.62 +/- 14.60 kg) volunteered for this
      study. Subjects had no history of lower extremity injury, vestibular or balance
      disorders, functional ankle instability, or head injury in the past 6 months.
      INTERVENTION(S): On separate days, subjects performed isokinetic fatiguing
      contractions of the plantar flexors and dorsiflexors in a 30% protocol (70%
      decrease in strength) and a 50% protocol (50% decrease in strength). MAIN OUTCOME
      MEASURE(S): Baseline and postfatigue postural stability scores were determined
      before and after the isokinetic fatiguing contractions. Plantar-flexion peak
      torque measurements were obtained for the 2 fatiguing protocols. Three prefatigue
      and 12 postfatigue postural stability trials were recorded. Velocities for
      testing were 60 degrees /s for plantar flexion and 120 degrees /s for
      dorsiflexion. RESULTS: Sway velocity was significantly greater when the ankle was
      fatigued to 30% (1.56 degrees /s) than in the 50% condition (1.36 degrees /s).
      For the 30% protocol, sway was significantly impaired when the pretest condition
      (1.19 degrees /s) was compared with posttest trial 1 (2.34 degrees /s), trial 2
      (2.37 degrees /s), and trial 3 (1.71 degrees /s). For the 50% protocol, sway was
      significantly impaired when the pretest condition (1.27 degrees /s) was compared
      with posttest trial 1 (2.02 degrees /s). CONCLUSIONS: The 30% fatigue protocol
      resulted in significantly longer impairment of postural stability than the 50%
      protocol. Because the 30% protocol resulted in a greater effect but was
      relatively short-lived (approximately 75 to 90 s), it is more useful for research
      purposes.

PMID- 16284642
TI  - Strength and fatigability of the dominant and nondominant hip abductors.
AB  - CONTEXT: Contralateral muscular imbalances have been suggested to increase the
      risk of lower extremity injury. Previous groups have assessed strength of the
      quadriceps and hamstring muscle groups; however, no previous authors have
      compared bilateral hip-abductor muscular performance. OBJECTIVE: To examine the
      strength and fatigability of the hip abductors in the dominant and nondominant
      legs. DESIGN: Single-group, repeated-measures design. SETTING: Musculoskeletal
      laboratory. PATIENTS OR OTHER PARTICIPANTS: Forty-two healthy subjects (23 males,
      19 females; age = 24.3 +/- 2.7 years, height = 173.4 +/- 9.8 cm, mass = 73.7 +/-
      11.6 kg). INTERVENTION(S): Subjects performed three 5-second maximal voluntary
      isometric contraction (MVIC) trials of the hip abductors with the dominant and
      nondominant legs. Following the maximal strength trials, subjects performed a
      submaximal (50% of MVIC) 30-second fatigue trial with each leg. MAIN OUTCOME
      MEASURE(S): Peak torque (PT) was recorded from each MVIC trial. Surface
      electromyography was used to record muscle activity during the fatigue trials.
      Power spectral analysis was used to determine the median frequency of each 0.512
      second portion of the fatigue trials. Median frequencies were plotted against
      time, and linear regression was used to determine the median frequency slope
      (MF(slope)). Data were analyzed using 2-tailed, paired t tests. RESULTS: Hip
      abduction PT of the dominant leg (81.0 +/- 23.7 Nm) was significantly larger than
      that of the nondominant leg (76.1 +/- 9.9 Nm, P = 0.02). There was no difference
      in MF(slope) between the dominant (-0.37 +/- 0.29) and nondominant limbs (-0.35
      +/- 0.34, P = 0.84). The PT and MF(slope) were not significantly correlated (r = 
      0.07, P = 0.53). CONCLUSIONS: Hip-abduction strength differences exist between
      the dominant and nondominant legs. Measures of strength and fatigability were
      poorly related; therefore, clinicians may opt to assess hip strength and
      fatigability independent of each another.

PMID- 16284643
TI  - The uncertainty (validity and reliability) of three electrothermometers in
      therapeutic modality research.
AB  - CONTEXT: Data from electrothermometers are used to determine therapeutic modality
      usage, but the value of experimental results is only as good as the data
      collected. OBJECTIVE: To determine the reliability and validity of 3
      electrothermometers from 2 manufacturers. DESIGN: A 3 x 4 x 17 factorial with
      repeated measures on 2 factors. Independent variables were trial (1, 2, 3),
      thermometer (mercury thermometer, Iso-Thermex calibrated from -50 degrees C to 50
      degrees C, Iso-Thermex calibrated from -20 degrees C to 80 degrees C, and
      Datalogger), and time (17). SETTING: Human Performance Research Center.
      INTERVENTION(S): Eighteen thermocouples were inserted through the wall of a
      foamed polystyrene cooler, and 6 were connected to each of the 3
      electrothermometers. The cooler was positioned on a stir plate and filled with
      room-temperature water (18.4 degrees C). A mercury thermometer was immersed into
      the water bath. Measurements of the water bath were taken every 10 seconds for
      three 3-minute trials. MAIN OUTCOME MEASURE(S): The temperature variability of 3
      electrothermometers was taken from a calibrated mercury thermometer. RESULTS: The
      Iso-Thermex electrothermometers did not differ statistically from each other in
      uncertainty (validity error +/- reliability error = 0.06 degrees C +/- 0.03
      degrees C +/- 0.03 degrees C +/- 0.02 degrees C, P < .05), but both differed from
      the Datalogger (0.64 degrees C +/- 0.20 degrees C, P < .05). The Datalogger
      temperature was consistently higher than the mercury thermometer temperature.
      CONCLUSIONS: The Iso-Thermex electrothermometers were more stable than the
      Datalogger, and values were within the published uncertainty (+/-0.1 degrees C)
      when used with PT-6 thermocouples. The Datalogger we used had an uncertainty of
      measurement greater than that indicated in the user's manual (approximately +/
      0.52 degrees C). Uncertainty of +/-0.84 degrees C can significantly influence the
      interpretation of results when intramuscular temperature changes are usually less
      than 5 degrees C.

PMID- 16284644
TI  - Self-reported comfort in athletic training of gender-specific and non-gender
      specific injuries and issues.
AB  - CONTEXT: To assist athletes in maintaining optimal health, athletic trainers must
      work with athletes of both sexes. OBJECTIVE: To examine athletic trainers'
      comfort levels in providing care for gender-specific and non-gender-specific
      injuries and issues. DESIGN: We mailed 235 Gender Comfort in Athletic Training
      Questionnaires to program directors, who were asked to distribute and collect
      them. SETTING: We randomly selected 21 athletic training education program
      directors and invited them by e-mail to participate in the study. Fourteen
      program directors representing the 10 National Athletic Trainers' Association
      districts agreed to participate. PATIENTS OR OTHER PARTICIPANTS: A total of 192
      participants returned completed questionnaires, for a response rate of 82% (103
      women, 89 men; 101 senior athletic training students, 91 certified athletic
      trainers). MAIN OUTCOME MEASURE(S): The questionnaire consisted of 17 injuries
      and issues common to both female and male athlete scenarios. Three gender
      specific items were added to each scenario. Responses were scored on a 5-point
      scale anchored by 1 (very uncomfortable) and 5 (very comfortable). Participants
      were asked to indicate the reason for any degree of discomfort. Internal
      consistency, determined by the Cronbach alpha, was .92 for the female athlete
      scenario and .93 for the male athlete scenario. RESULTS: We found significant
      differences between women and men certified athletic trainers for the female and
      male athlete scenarios. Overall, women were more comfortable caring for female
      injuries and issues, whereas men were more comfortable caring for male injuries
      and issues. Certified athletic trainers reported more comfort overall than
      athletic training students. The most common underlying reason reported for
      discomfort in caring for female and male injuries and issues was experience
      level. CONCLUSIONS: Athletic training education programs should provide early and
      more deliberate experiences with injuries and issues of a more intimate nature,
      including those that are gender specific and non-gender specific. These
      experiences may increase athletic trainers' level of comfort in providing care to
      athletes of the opposite sex.

PMID- 16284645
TI  - Stretching before and after exercise: effect on muscle soreness and injury risk.

PMID- 16284646
TI  - Effectiveness of rehabilitation for patients with subacromial impingement
      syndrome.

PMID- 16284648
TI  - The mitochondrial origin of postischemic arrhythmias.
AB  - Recovery of the mitochondrial inner membrane potential (DeltaPsi(m)) is a key
      determinant of postischemic functional recovery of the heart. Mitochondrial ROS
      induced ROS release causes the collapse of DeltaPsi(m) and the destabilization of
      the action potential (AP) through a mechanism involving a mitochondrial inner
      membrane anion channel (IMAC) modulated by the mitochondrial benzodiazepine
      receptor (mBzR). Here, we test the hypothesis that this mechanism contributes to
      spatiotemporal heterogeneity of DeltaPsi(m) during ischemia-reperfusion (IR),
      thereby promoting abnormal electrical activation and arrhythmias in the whole
      heart. High-resolution optical AP mapping was performed in perfused guinea pig
      hearts subjected to 30 minutes of global ischemia followed by reperfusion.
      Typical electrophysiological responses, including progressive AP shortening
      followed by membrane inexcitablity in ischemia and ventricular fibrillation upon
      reperfusion, were observed in control hearts. These responses were reduced or
      eliminated by treatment with the mBzR antagonist 4'-chlorodiazepam (4'-Cl-DZP),
      which blocks depolarization of DeltaPsi(m). When applied throughout the IR
      protocol, 4'-Cl-DZP blunted AP shortening and prevented reperfusion arrhythmias.
      Inhibition of ventricular fibrillation was also achieved by bolus infusion of 4'
      Cl-DZP just before reperfusion. Conversely, treatment with an agonist of the mBzR
      that promotes DeltaPsi(m) depolarization exacerbated IR-induced
      electrophysiological changes and failed to prevent arrhythmias. The effects of
      these compounds were consistent with their actions on IMAC and DeltaPsi(m). These
      findings directly link instability of DeltaPsi(m) to the heterogeneous
      electrophysiological substrate of the postischemic heart and highlight the
      mitochondrial membrane as a new therapeutic target for arrhythmia prevention in
      ischemic heart disease.

PMID- 16284649
TI  - Reduced mitochondrial density and increased IRS-1 serine phosphorylation in
      muscle of insulin-resistant offspring of type 2 diabetic parents.
AB  - To further explore the nature of the mitochondrial dysfunction and insulin
      resistance that occur in the muscle of young, lean, normoglycemic, insulin
      resistant offspring of parents with type 2 diabetes (IR offspring), we measured
      mitochondrial content by electron microscopy and insulin signaling in muscle
      biopsy samples obtained from these individuals before and during a
      hyperinsulinemic-euglycemic clamp. The rate of insulin-stimulated muscle glucose
      uptake was approximately 60% lower in the IR offspring than the control subjects
      and was associated with an approximately 60% increase in the intramyocellular
      lipid content as assessed by H magnetic resonance spectroscopy. Muscle
      mitochondrial density was 38% lower in the IR offspring. These changes were
      associated with a 50% increase in IRS-1 Ser312 and IRS-1 Ser636 phosphorylation
      and an approximately 60% reduction in insulin-stimulated Akt activation in the IR
      offspring. These data provide new insights into the earliest defects that may be
      responsible for the development of type 2 diabetes and support the hypothesis
      that reductions in mitochondrial content result in decreased mitochondrial
      function, which predisposes IR offspring to intramyocellular lipid accumulation,
      which in turn activates a serine kinase cascade that leads to defects in insulin
      signaling and action in muscle.

PMID- 16284647
TI  - National Athletic Trainers' Association position statement: management of asthma
      in athletes.
AB  - OBJECTIVE: To present guidelines for the recognition, prophylaxis, and management
      of asthma that lead to improvement in the quality of care certified athletic
      trainers and other heath care providers can offer to athletes with asthma,
      especially exercise-induced asthma. BACKGROUND: Many athletes have difficulty
      breathing during or after athletic events and practices. Although a wide variety
      of conditions can predispose an athlete to breathing difficulties, the most
      common cause is undiagnosed or uncontrolled asthma. At least 15% to 25% of
      athletes may have signs and symptoms suggestive of asthma, including exercise
      induced asthma. Athletic trainers are in a unique position to recognize breathing
      difficulties caused by undiagnosed or uncontrolled asthma, particularly when
      asthma follows exercise. Once the diagnosis of asthma is made, the athletic
      trainer should play a pivotal role in supervising therapies to prevent and
      control asthma symptoms. It is also important for the athletic trainer to
      recognize when asthma is not the underlying cause for respiratory difficulties,
      so that the athlete can be evaluated and treated properly. RECOMMENDATIONS: The
      recommendations contained in this position statement describe a structured
      approach for the diagnosis and management of asthma in an exercising population.
      Athletic trainers should be educated to recognize asthma symptoms in order to
      identify patients who might benefit from better management and should understand
      the management of asthma, especially exercise-induced asthma, to participate as
      active members of the asthma care team.

PMID- 16284650
TI  - Role of CCR5 in IFN-gamma-induced and cigarette smoke-induced emphysema.
AB  - Th1 inflammation and remodeling characterized by tissue destruction frequently
      coexist in human diseases. To further understand the mechanisms of these
      responses, we defined the role(s) of CCR5 in the pathogenesis of IFN-gamma
      induced inflammation and remodeling in a murine emphysema model. IFN-gamma was a
      potent stimulator of the CCR5 ligands macrophage inflammatory protein-1alpha/CCL
      3 (MIP-1alpha/CCL-3), MIP-1beta/CCL-4, and RANTES/CCL-5, among others. Antibody
      neutralization or null mutation of CCR5 decreased IFN-gamma-induced inflammation,
      DNA injury, apoptosis, and alveolar remodeling. These interventions decreased the
      expression of select chemokines, including CCR5 ligands and MMP-9, and increased
      levels of secretory leukocyte protease inhibitor. They also decreased the
      expression and/or activation of Fas, FasL, TNF, caspase-3, -8, and -9, Bid, and
      Bax. In accordance with these findings, cigarette smoke induced pulmonary
      inflammation, DNA injury, apoptosis, and emphysema via an IFN-gamma-dependent
      pathway(s), and a null mutation of CCR5 decreased these responses. These studies
      demonstrate that IFN-gamma is a potent stimulator of CC and CXC chemokines and
      highlight the importance of CCR5 in the pathogenesis of IFN-gamma-induced and
      cigarette smoke-induced inflammation, tissue remodeling, and emphysema. They also
      demonstrate that CCR5 is required for optimal IFN-gamma stimulation of its own
      ligands, other chemokines, MMPs, caspases, and cell death regulators and the
      inhibition of antiproteases.

PMID- 16284653
TI  - Scanning Kelvin nanoprobe detection in materials science and biochemical
      analysis.
AB  - The Kelvin nanoprobe is an extremely sensitive instrument capable of discerning
      subtle molecular interactions using vibrating electromagnetic and acoustic
      fields. It is based on the measurement of a fundamental material property, the
      work function. Modulation of this substrate parameter is caused by the adsorption
      or desorption of molecules, oxidation, corrosion, contamination, mechanical
      stress, illumination, temperature changes, electrostatic charging, surface
      treatment, attached dipolar structures and/or the immobilization of biomolecules.
      The present article explains the general principles of the method and offers an
      indication of the wide range of possible applications, with an emphasis on
      potential use in the biotechnological arena.

PMID- 16284655
TI  - Microplate-based screening methods for the efficient development of sandwich
      immunoassays.
AB  - The selection of suitable antibodies is a critical step in immunoassay
      development, since the final assay performance is predetermined by this decision
      to a large extent. Particularly, the screening for matching pairs in sandwich
      immunoassays is difficult, if both antibodies are derived from one species or
      when monoclonal antibodies are only available as cell supernatants. Several
      microplate-based approaches for in situ labeling of detection antibodies were
      tested, in order to avoid time consuming purification of antibodies for enzyme
      conjugate synthesis. We investigated labeling with anti-species antibodies and
      Fab fragments thereof, labeling with protein G and biotinylation of cell
      supernatants without prior purification. Antibodies against peanut proteins were
      used as a model and signal-to-blank ratios were used in all cases as a measure of
      the antibody pair performance. Amongst the investigated approaches, preincubation
      of the detection antibody with labeled anti-species antibody turned out to be
      most suitable under our conditions. Diagrams, showing the performance of all
      possible antibody combinations, were generated with this method and were compared
      to results obtained with covalently labeled detection antibodies. Finally, a
      flowchart is presented, suggesting an efficient strategy for the development of
      highly sensitive sandwich immunoassays.

PMID- 16284654
TI  - 1,6-Hexanedithiol monolayer as a receptor for specific recognition of
      alkylmercury.
AB  - 1,6-Hexanedithiol monolayer acts as an unusually specific recognition agent for
      CH3Hg+ when the microcantilever is used as the transducer; the mechanism of the
      sensor is discussed.

PMID- 16284651
TI  - Complete FcRn dependence for intravenous Ig therapy in autoimmune skin blistering
      diseases.
AB  - Numerous mechanisms of action have been proposed for intravenous Ig (IVIG). In
      this study, we used IgG passive transfer murine models of bullous pemphigoid
      (BP), pemphigus foliaceus (PF), and pemphigus vulgaris (PV) to test the
      hypothesis that the effect of IVIG in autoantibody-mediated cutaneous bullous
      diseases is to accelerate the degradation of pathogenic IgG by saturation of the
      MHC-like Fc receptor neonatal Fc receptor (FcRn). BP, PF, and PV are organ
      specific antibody-mediated diseases in which autoantibodies target the
      hemidesmosomal antigen BP180 and desmosomal antigens Dsg1 and Dsg3, respectively.
      Antibodies against BP180, Dsg1, and Dsg3, when injected into neonatal mice,
      induce the BP, PF, and PV disease phenotypes, respectively. We found that FcRn
      deficient mice were resistant to experimental BP, PF, and PV. Circulating levels
      of pathogenic IgG in FcRn-deficient mice were significantly reduced compared with
      those in WT mice. Administration of high-dose human IgG (HDIG) to WT mice also
      drastically reduced circulating pathogenic IgG levels and prevented blistering.
      In FcRn-deficient mice, no additional protective effect with HDIG was realized.
      These data demonstrate that the therapeutic efficacy of HDIG treatment in the
      pemphigus and pemphigoid models is dependent on FcRn. Thus, FcRn is a promising
      therapeutic target for treating such IgG-mediated autoimmune diseases.

PMID- 16284652
TI  - Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron
      specific LEPR-B transgenes.
AB  - We have generated mice that carry a neuron-specific leptin receptor (LEPR)
      transgene whose expression is driven by the rat synapsin I promoter synapsin-LEPR
      B (SYN-LEPR-B). We have also generated mice that are compound hemizygotes for the
      transgenes SYN-LEPR-B and neuron-specific enolase-LEPR B (NSE-LEPR-B). We
      observed a degree of correction in db/db mice that are hemizygous (Syn db/db) and
      homozygous (Syn/Syn db/db) for the SYN-LEPR-B transgene similar to that
      previously reported for the NSE-LEPR-B transgene. We also show complete
      correction of the obesity and related phenotypes of db/db mice that are
      hemizygous for both NSE-LEPR-B and SYN-LEPR-B transgenes (Nse+Syn db/db). Body
      composition, insulin sensitivity, and cold tolerance were completely normalized
      in Nse+Syn db/db mice at 12 weeks of age compared with lean controls. In situ
      hybridization for LEPR B isoform expression in Nse+Syn db/db mice showed robust
      expression in the energy homeostasis-relevant regions of the hypothalamus.
      Expression of 3 neuropeptide genes, agouti-related peptide (Agrp), neuropeptide Y
      (Npy), and proopiomelanocortin (Pomc), was fully normalized in dual transgenic
      db/db mice. The 2 transgenes in concert conferred normal fertility to male and
      female db/db mice. Male mice with partial peripheral deletion of Lepr, induced in
      the periweaning phase, did not show alterations in body composition or mass. In
      summary, we show that brain-specific leptin signaling is sufficient to reverse
      the obesity, diabetes, and infertility of db/db mice.

PMID- 16284656
TI  - Highly reproducible hybridization assay of zeptomole DNA based on adsorption of
      nanoparticle-bioconjugate.
AB  - A nanoparticle-bioconjugate was formed by homogeneous hybridization of one
      polynucleotide target with two oligonucleotide probes labelled by thiol and a
      nanoparticle, respectively. Deposition of the nanoparticle-bioconjugate on a gold
      surface by thiol-gold reaction was monitored in situ by quartz crystal
      microbalance (QCM) and applied for flow analysis of zeptomole amounts of
      polynucleotide. The formation in solution and adsorption of thiolated conjugates
      on gold could be fast, uniform and effective, and has been successfully exploited
      to construct a highly reproducible and sensitive platform for detection of target
      sequences. Being more rapid, reproducible, sensitive and amenable to automation
      than previously reported microgravimetric hybridization assays, this technology
      has great promise for practical applications in molecular diagnostics.

PMID- 16284657
TI  - Continuous wave cavity ring-down spectroscopy measurement of NO2 mixing ratios in
      ambient air.
AB  - The performance of a continuous wave diode laser based cavity ring-down (CRD)
      spectrometer is demonstrated for retrieval of NO2 mixing ratios in ambient air.
      Measurements are made at wavelengths around 410 nm, a region free from other
      spectroscopic interferences, and the instrument is shown to be capable of
      quantitative and precise NO2 mixing ratio determinations without any requirement
      for calibration. The minimum concentration of NO2 that can be measured by the
      spectrometer is estimated to be 0.1 ppbv (parts per billion by volume) in 50 s at
      atmospheric pressure. Using dynamic dilution of a standard NO2 sample, the
      performance of the spectrometer has been validated for NO2 measurements over the
      range of 0.2 to 80 ppbv. NO2 measurements performed directly on laboratory air
      are compared with data obtained with a calibrated chemiluminescence instrument
      and shown to be in excellent agreement.

PMID- 16284658
TI  - HPLC imprinted-stationary phase prepared by precipitation polymerisation for the
      determination of thiabendazole in fruit.
AB  - A molecularly imprinted polymer (MIP) tailored for the HPLC determination of the
      fungicide thiabendazole (TBZ) has been synthesised in one single preparative step
      by precipitation polymerisation in an acetonitrile/toluene co-solvent, using TBZ
      as template molecule, methacrylic acid as functional monomer and divinylbenzene
      80 as crosslinker. The imprinted polymer particulates obtained were characterised
      by scanning electron microscopy and nitrogen sorption porosimetry. These analyses
      showed clearly that spherical polymer particulates (polymer microspheres) with
      narrow size distributions (average particle diameter approximately 3.5 microm)
      and well-developed pore structures had been produced. The imprinted microspheres
      were packed into a stainless steel HPLC column (50 x 4.6 mm id) and evaluated as
      an imprinted stationary phase. The imprinting effect was demonstrated clearly,
      i.e., the column was observed to bind TBZ selectively, and the effect of
      different chromatographic parameters (e.g., temperature, flow-rate and elution
      solvents) on TBZ retention/elution studied. Under optimised conditions, the TBZ
      imprinted column was used for the HPLC-fluorescence (HPLC-F) determination of TBZ
      directly from orange (both whole fruit and juice), lemon, grape and strawberry
      extracts at low concentration levels in less than 15 min, without any need for a
      clean-up step in the analytical protocol.

PMID- 16284659
TI  - Validation of new microvolume Couette flow linear dichroism cells.
AB  - Long molecules such as fibrous proteins are particularly difficult to
      characterise structurally. We have recently designed a microvolume Couette flow
      linear dichroism (LD) cell whose sample volume is only 20-40 microL in contrast
      to previous cells where the volume of sample required has typically been of the
      order of 1000-2000 microL. This brings the sample requirements of LD to a level
      where it can be used for biological samples. Since LD is the difference in
      absorption of light polarised parallel to an orientation direction and
      perpendicular to that direction, it is the ideal technique for determining
      relative orientations of subunits of e.g. fibrous proteins, DNA-drug systems,
      etc. For solution phase samples, Couette flow orientation, whereby the sample is
      sandwiched between two cylinders, one of which rotates, has proved to be the
      optimal technique for LD experiments in many laboratories. Our capillary
      microvolume LD cell has been designed using extruded quartz rods and capillaries
      and focusing and collecting lenses. We have developed applications with PCR
      products, fibrous proteins, liposome-bound membrane proteins, as well as DNA-dye
      systems. Despite this range of applications, to date there is nothing reported in
      the literature to enable one to validate the performance of Couette flow LD
      cells. In this paper we establish validation criteria and show that the data from
      the microvolume cells are reproducible, vary by less than 1% with sample
      reloading, follow the Beer-Lambert law, and have signals linear in voltage over a
      wide voltage range. The microvolume cell data are consistent with those from the
      large-volume cells for DNA samples. Surprisingly, upon extending the wavelength
      range by adding the intercalator ethidium bromide, the spectra in the microvolume
      and large-volume cells differ by a wavelength dependent orientation parameter.
      This wavelength variation was concluded to be the result of Taylor-vortices in
      the large-volume cells which have inner rotating cylinders in our laboratory.
      Thus the microvolume LD cells can be concluded to provide better data than our
      large-volume LD cells, though the latter are still to be preferred for titration
      series as it is extremely difficult to add sample to the capillary cells without
      introducing artefacts.

PMID- 16284660
TI  - Flow-through sensor with Fourier transform Raman detection for determination of
      sulfonamides.
AB  - A flow-through sensor system with Fourier transform (FT) Raman spectroscopy as
      detection technique is described. The molecular and structural information
      contained in Raman spectra together with the selective retention of the species
      of interest on the sorbent make the proposed methodology highly selective. The
      flow-through sensor allowed the direct quantitative determination of
      sulfathiazole and sulfamethoxazole in the presence of other species that are
      normally encountered with these analytes. The system used Sephadex QAE A-25 resin
      as packing material of a flow-through cell on which sulfonamides were temporarily
      retained. Samples were transported by a carrier solution of NaOH 10(-2) mol l(-1)
      (pH = 12), and 2 ml of a [NaCl (0.10 mol l(-1))/NaOH (10(-2) mol l(-1))] solution
      was employed as eluent. Using a sample volume of 1 ml, the analytical signal was
      linear in the range 0.5-7 g l(-1) and 0.5-10 g l(-1), for sulfathiazole and
      sulfamethoxazole, respectively. RSDs (%) lower than 4% were obtained for both
      analytes. The sensor was satisfactorily applied to several commercial
      pharmaceutical preparations for human and animals in different physical
      presentations, including capsules, syrup, tablets, powders, injectables and
      suspensions.

PMID- 16284661
TI  - Rapid in situ detection of alkaloids in plant tissue under ambient conditions
      using desorption electrospray ionization.
AB  - Desorption electrospray ionization (DESI) mass spectrometry is applied to the in
      situ detection of alkaloids in the tissue of poison hemlock (Conium maculatum),
      jimsonweed (Datura stramonium) and deadly nightshade (Atropa belladonna). The
      experiment is carried out by electrospraying micro-droplets of solvent onto
      native or freshly-cut plant tissue surfaces. No sample preparation is required
      and the mass spectra are recorded under ambient conditions, in times of a few
      seconds. The impact of the sprayed droplets on the surface produces gaseous ions
      from organic compounds originally present in the plant tissue. The effects of
      operating parameters, including the electrospray high voltage, heated capillary
      temperature, the solvent infusion rate and the carrier gas pressure on analytical
      performance are evaluated and optimized. Different types of plant material are
      analyzed including seeds, stems, leaves, roots and flowers. All the previously
      reported alkaloids have been detected in C. maculatum, while fifteen out of
      nineteen known alkaloids for D. stramonium and the principal alkaloids of A.
      belladonna were also identified. All identifications were confirmed by tandem
      mass spectrometry. Results obtained show similar mass spectra, number of
      alkaloids, and signal intensities to those obtained when extraction and
      separation processes are performed prior to mass spectrometric analysis. Evidence
      is provided that DESI ionization occurs by both a gas-phase ionization process
      and by a droplet pick-up mechanism. Quantitative precision of DESI is compared
      with conventional electrospray ionization mass spectrometry (after sample workup)
      and the RSD values for the same set of 25 dicotyledonous C. maculatum seeds (one
      half of each seed analyzed by ESI and the other by DESI) are 9.8% and 5.2%,
      respectively.

PMID- 16284662
TI  - Determination of affinity constants of locked nucleic acid (LNA) and DNA duplex
      formation using label free sensor technology.
AB  - Locked nucleic acid (LNA) is a nucleic acid analogue containing 2'-O,4'-C
      methylene-beta-D-ribofuranosyl nucleotides, which have a bicyclic furanose unit
      locked in a RNA mimicking sugar conformation. Oligonucleotides containing LNA
      monomers show an enhanced thermal stability and robustness against nuclease
      mediated cleavage. Therefore special tailored LNA is a versatile tool for gene
      array analysis and single nucleotide polymorphism (SNP) analysis. The higher
      melting temperatures result from a higher affinity between the LNA and its
      complementary base. This was verified by the determination of the affinity
      constants of the duplex formation of 3 oligonucleotides: DNA, L-DNA, in which all
      thymidines are substituted by LNA, and a fully modified LNA, to their
      complementary DNA strand. Affinity constants were calculated to be 1.5 x 10(9),
      4.0 x 10(9) and >10(12) L mol(-1). This was done using the label free and time
      resolved sensing technology reflectometric interference spectroscopy (RIfS), in
      an assay format similar to a titration called binding inhibition assay.

PMID- 16284663
TI  - Identification and quantification of enrofloxacine in poultry feeding water
      through excitation emission fluorescence and three-way PARAFAC calibration.
AB  - In this work an excitation emission molecular fluorescence technique with PARAFAC
      calibration is proposed for enrofloxacine determination in feeding water from
      poultry farms. In accordance with the working criteria of the 2002/657/EC
      European Decision, the proposed method has a capability of detection, CCbeta, of
      6.8 microg l(-1), for both probabilities of false positive and false negative of
      5%. The accuracy of the method is demonstrated and its precision is 1.7 microg l(
      1), expressed as standard deviation. This method allows one to identify and
      determine the quantity of enrofloxacine present in water samples from poultry
      farms without it being necessary to determine the possible interferents, nor
      separate them in a step previous to calibration.

PMID- 16284664
TI  - Rapid identification of closely related muscle foods by vibrational spectroscopy
      and machine learning.
AB  - Muscle foods are an integral part of the human diet and during the last few
      decades consumption of poultry products in particular has increased
      significantly. It is important for consumers, retailers and food regulatory
      bodies that these products are of a consistently high quality, authentic, and
      have not been subjected to adulteration by any lower-grade material either by
      accident or for economic gain. A variety of methods have been developed for the
      identification and authentication of muscle foods. However, none of these are
      rapid or non-invasive, all are time-consuming and difficulties have been
      encountered in discriminating between the commercially important avian species.
      Whilst previous attempts have been made to discriminate between muscle foods
      using infrared spectroscopy, these have had limited success, in particular
      regarding the closely related poultry species, chicken and turkey. Moreover, this
      study includes novel data since no attempts have been made to discriminate
      between both the species and the distinct muscle groups within these species, and
      this is the first application of Raman spectroscopy to the study of muscle foods.
      Samples of pre-packed meat and poultry were acquired and FT-IR and Raman
      measurements taken directly from the meat surface. Qualitative interpretation of
      FT-IR and Raman spectra at the species and muscle group levels were possible
      using discriminant function analysis. Genetic algorithms were used to elucidate
      meaningful interpretation of FT-IR results in (bio)chemical terms and we show
      that specific wavenumbers, and therefore chemical species, were discriminatory
      for each type (species and muscle) of poultry sample. We believe that this
      approach would aid food regulatory bodies in the rapid identification of meat and
      poultry products and shows particular potential for rapid assessment of food
      adulteration.

PMID- 16284665
TI  - All-solid-state reference electrodes based on conducting polymers.
AB  - A novel construction of solution free (pseudo)reference electrodes, compatible
      with all-solid-state potentiometric indicator electrodes, has been proposed.
      These electrodes use conducting polymers (CP): polypyrrole (PPy) or poly(3,4
      ethylenedioxythiophene) (PEDOT). Two different arrangements have been tested:
      solely based on CP and those where the CP phase is covered with a poly(vinyl
      chloride) based outer membrane of tailored composition. The former arrangement
      was designed to suppress or compensate cation- and anion-exchange, using mobile
      perchlorate ions and poly(4-styrenesulfonate) or dodecylbenzenesulfonate anions
      as immobilized dopants. The following systems were used: (i) polypyrrole layers
      doped simultaneously by two kinds of anions, both mobile and immobilized in the
      polymer layer; (ii) bilayers of polypyrrole with anion exchanging inner layer and
      cation-exchanging outer layer; (iii) polypyrrole doped by surfactant
      dodecylbenzenesulfonate ions, which inhibit ion exchange on the polymer/solution
      interface. For the above systems, recorded potentials have been found to be
      practically independent of electrolyte concentration. The best results, profound
      stability of potentials, have been obtained for poly(3,4-ethylenedioxythiophene)
      or polypyrrole doped by poly(4-styrenesulfonate) anions covered by a poly(vinyl
      chloride) based membrane, containing both anion- and cation-exchangers as well as
      solid potassium chloride and silver chloride with metallic silver. Differently to
      the cases (i)-(iii) these electrodes are much less sensitive to the influence of
      redox and pH interferences. This arrangement has been also characterized using
      electrochemical impedance spectroscopy and chronopotentiometry.

PMID- 16284666
TI  - Oxygen indicators and intelligent inks for packaging food.
AB  - The detection of oxygen using optical sensors is of increasing interest,
      especially in modified atmosphere food packaging (MAP), in which the package,
      usually containing food, is flushed with a gas, such as carbon dioxide or
      nitrogen. This tutorial review examines the ideal properties of an oxygen optical
      sensor for MAP and compares them with those developed to date, including the most
      recent advances. The basic technologies underpinning the different indicator
      types are described, examples given and their potential for application in MAP
      assessed. This tutorial review should be of interest to the MAP industry and
      researchers in optical sensors and oxygen sensing.

PMID- 16284667
TI  - Simple models for hydrophobic hydration.
AB  - This tutorial review compares models that describe DeltaG(cavitation). Their
      qualitative agreement suggests the use of the simple, time-honored Pierotti
      equation. Its coefficients, fine-tuned with atomistic simulations, give a revised
      Pierotti approach, rPA. A discussion of the extension of the rPA model to non
      spherical solutes is presented and the different roles of molecular volume and
      surface area of the solute are brought together. The tutorial review is aimed at
      experimentalists and theoreticians interested in the description of solvent
      effects.

PMID- 16284668
TI  - Advances in chemistry applied to forensic science.
AB  - Acts of terrorism, an increase in the use of firearms, drug abuse, the use of so
      called date-rape drugs, and driving whilst under the influence of drugs, are just
      some of the subjects frequently in the news. In the absence of fingermarks and of
      material leading to the recovery of DNA, the forensic scientist has to rely upon
      chemical analysis of trace amounts of materials including explosives, drugs,
      toxicological specimens, firearms discharge residues, fibres, glass, paint, soil
      etc., in order to establish or eliminate links between suspect and victim and/or
      scene. This tutorial review describes analytical problems facing the forensic
      chemist, and the current methods and techniques employed to tackle them.

PMID- 16284669
TI  - Chemistry of N-fluoropyridinium salts.
AB  - This tutorial review deals with developments in the chemistry of N
      fluoropyridinium salts in the past decade, including both synthetic and
      mechanistic aspects. Three distinct types of transformations including: i)
      fluorination reactions, ii) carbenoid behavior and iii) cine-/tele- substitution
      involving N-fluoropyridinium cation are exemplified. Procedures for fluorination
      of carbanions and benzenoid aromatics along with hetarylation processes yielding
      2- and 4-substituted pyridines are referenced. Several new discoveries in the
      area, including three-component condensation reactions of in situ generated N
      fluoropyridinium fluoride are described.

PMID- 16284670
TI  - Coordination chemistry and functionalization of white phosphorus via transition
      metal complexes.
AB  - The chemistry of phosphorus is nowadays rivaling that of carbon in terms of
      complexity and diversity. This tutorial review highlights the state-of-the-art in
      the field of metal-mediated activation and functionalization of white phosphorus.
      Particular attention is given to an illustration of the coordination abilities of
      the intact molecule as well as the disaggregating and reaggregating metal
      mediated processes resulting in different polyphosphorus ligands from P(1) to
      P(12). The metal-promoted P-C and P-H bond forming processes are also reviewed
      showing that an ecoefficient catalytic protocol for transforming P(4) into high
      value organophosphorus compounds is a concrete possibility for chemical
      companies. This tutorial review deals with the activation and functionalization
      of white phosphorus in the coordination sphere of transition metal complexes.
      Particular attention is given to the coordination abilities of the intact
      molecule as well as to the disaggregating and reaggregating metal-mediated
      processes yielding various polyphosphorus ligands from P(1) to P(12). The metal
      promoted processes for P-C and P-H bond formation are also reviewed showing that
      an ecoefficient catalytic protocol for transforming P(4) into high value
      organophosphorus compounds offers good opportunities for chemical companies.

PMID- 16284671
TI  - Taking advantage of luminescent lanthanide ions.
AB  - Lanthanide ions possess fascinating optical properties and their discovery, first
      industrial uses and present high technological applications are largely governed
      by their interaction with light. Lighting devices (economical luminescent lamps,
      light emitting diodes), television and computer displays, optical fibres, optical
      amplifiers, lasers, as well as responsive luminescent stains for biomedical
      analysis, medical diagnosis, and cell imaging rely heavily on lanthanide ions.
      This critical review has been tailored for a broad audience of chemists,
      biochemists and materials scientists; the basics of lanthanide photophysics are
      highlighted together with the synthetic strategies used to insert these ions into
      mono- and polymetallic molecular edifices. Recent advances in NIR-emitting
      materials, including liquid crystals, and in the control of luminescent
      properties in polymetallic assemblies are also presented. (210 references.).

PMID- 16284672
TI  - Bridging the gap between physician specialists: a role for the College of
      Physicians, Singapore.

PMID- 16284673
TI  - The incidence and patterns of BCR/ABL rearrangements in chronic myeloid leukaemia
      (CML) using fluorescence in situ hybridisation (FISH).
AB  - INTRODUCTION: Chronic myeloid leukaemia (CML) is characterised by the formation
      of the BCR/ABL fusion gene, usually as a result of the Philadelphia (Ph)
      translocation between chromosomes 9 and 22. MATERIALS AND METHODS: The incidence
      of both typical and atypical BCR/ ABL gene rearrangements was determined in 110
      patients suspected of CML using dual fusion fluorescence in situ hybridisation
      (DF-FISH) probes. RESULTS: Eighty-seven per cent of CML patients showed Ph
      translocation while 13% were negative for the Ph chromosome. About 71.9% of Ph
      positive patients displayed the typical DF-FISH signal pattern. Atypical patterns
      among the Ph-positive patients included the concurrent loss of residual proximal
      9q and distal 22q (10.4%), complex translocation with additional partners (9.4%),
      supernumerary Ph (3.1%), loss of residual 9q sequences proximal to breakpoint
      (3.1%), and deletion of distal derivative 22q signal (2.1%). Cryptic genetic
      alterations with loss of proximal 9q sequences were found in 13.5% of CML Ph
      positive patients, which is associated with poor prognosis. Fusion signals were
      detected in 57.1% of CML Ph-negative patients, indicating cryptic BCR/ABL
      rearrangements (i.e., masked Ph). CONCLUSION: FISH is able to detect BCR/ABL
      fusion in CML with masked or variant Ph not apparent with conventional
      karyotyping. Establishment of signal patterns with FISH is important as atypical
      patterns may have clinical prognostic implications.

PMID- 16284674
TI  - An assessment of electronically captured data in the patient care enhancement
      system (PACES) for syndromic surveillance.
AB  - INTRODUCTION: A common approach to the surveillance of emerging infectious
      diseases and agents of bioterrorism is to analyse electronically captured data
      for disease syndromes. The Patient Care Enhancement System (PACES) is a form of
      electronic medical records presently in service in the Singapore Armed Forces
      (SAF). We assess the feasibility of PACES data for surveillance, describe time
      trends, and identify methods of sub-analysis which could improve performance.
      MATERIALS AND METHODS: Medical consults from July 2000 to June 2003 were
      extracted. Diagnosis codes were mapped to 7 infectious disease syndromes
      according to the categorisation in the Electronic Surveillance System for the
      Early Notification of Community-based Epidemics (ESSENCE): gastrointestinal (GI),
      fever (FEVER), respiratory, (RESP), coma (COMA), neurological (NEURO),
      dermatologic-haemorrhagic (DERMHEM) and dermatologic- infectious (DERM-INF).
      RESULTS: A total of 732,233 episodes of care were analysed. Weekly periodicity
      was observed, with decreased weekend consults; there were no obvious seasonal
      trends in any of the syndromes. RESP, FEVER and GI syndromes were common events.
      Sub-analyses, either by restricting to cases with a repeated consultation, or
      grouping the data by medical centres, could dramatically lower thresholds used to
      flag outbreaks. CONCLUSION: In spite of the level of background noise inherent in
      a system consisting mainly of primary care consults, sub-analysis by medical
      centre, or restriction to cases with repeated consults were able to yield
      sensitive thresholds for outbreak detection.

PMID- 16284675
TI  - Broadband ultrasound attention reference database for southeast Asian males and
      females.
AB  - INTRODUCTION: The objective of this study was to establish the broadband
      ultrasound attenuation (BUA) measurements of the calcaneum for Southeast Asian
      males and females. A database was used to draw the reference curve for the
      Southeast Asian male and female population. MATERIALS AND METHODS: The database
      included 366 healthy females and 236 healthy males. We measured the BUA values of
      the left heel using the Contact Ultrasound Bone Analyser (CUBA) clinical system.
      RESULTS: The mean difference between Southeast Asian males and Caucasian males
      was 9.3 dB MHz-1 and that for females was 5.0 dB MHz-1. The standard deviations
      (SDs) for Southeast Asian female and male normative values were 17.43 and 20.10,
      respectively. This is comparable with the SD for the McCue Caucasian female and
      male normative data of 16.54 and 17.45 respectively. CONCLUSION: The study shows
      that the Southeast Asian population has a significantly lower normative value
      than the Caucasian population. This BUA reference database obtained will allow
      for more accurate determination of Southeast Asian patients at risk of
      osteoporosis.

PMID- 16284676
TI  - Tuberculosis peritonitis in Negara Brunei Darussalam.
AB  - INTRODUCTION: Tuberculosis peritonitis (TBP) is uncommon and symptoms can be non
      specific. Local data are lacking and our aim is to review our local experience
      with TBP. MATERIALS AND METHODS: Between the period of 1996 to 2004, there were
      10 [male: 6; mean age, 48 +/- 18.5 years (range, 26 to 73)] cases of
      histologically documented TBP. Comparisons were made with pulmonary tuberculosis
      (PTB) patients. RESULTS: The overall prevalence ranged from 0% to 1.01% of all TB
      infections. The median duration of symptoms before diagnosis was 2 months (range,
      3 days to 24 months). Five patients (50%) had comorbid conditions and 3 patients
      (30%) had a history of positive contact. Presenting symptoms were abdominal
      distension (70%), abdominal pain (60%), fever (60%), anorexia (60%) and weight
      loss (40%). Two patients had pulmonary symptoms: cough/dyspnoea (n = 1) and cough
      (n = 1). Chest x-ray changes consistent with PTB were seen in 30%. TBP was
      diagnosed by laparoscopy (n = 6), laparotomy (n = 3) and blind peritoneal biopsy
      (n = 1). Adverse effects of TB drugs occurred in 80%, consisting of hepatitis (n
      = 4), nausea/vomiting (n = 2), rash (n = 1) and encephalopathy (n = 1).
      Haemoglobin (P = 0.026) and serum albumin levels (P = 0.002) were significantly
      lower in TBP patients. There was a significantly greater number of adverse
      effects (P <0.001). There were no significant differences between TBP and PTB
      with regard to age, non-specific symptoms (weight loss, anorexia and fever) and
      erythrocyte sedimentation rate. All were treated with standard regimes and there
      were no mortalities. CONCLUSIONS: TBP is uncommon in our population. TBP patients
      had significantly lower haemoglobin and serum albumin levels. They also
      experienced more adverse events during treatment. There were no differences in
      non-specific symptoms between TBP and PTB.

PMID- 16284677
TI  - Clinical characteristics of patients with multiple system atrophy in Singapore.
AB  - INTRODUCTION: Our study aimed to describe the clinical features of multiple
      system atrophy (MSA) in Singapore and verify its diagnosis using the consensus
      statement in the diagnosis of MSA. MATERIALS AND METHODS: All patients suspected
      to have MSA between 1995 and March 2005 were identified from the Movement
      Disorders database and the autonomic function testing results. The medical
      records were reviewed using a standardised data collection form. The diagnosis of
      MSA was verified using the consensus statement. Disease progression was evaluated
      using 2 pre-determined events: aid-requiring walking and wheelchair use. RESULTS:
      Seventy-two per cent (33/46) fulfilled the consensus statement. There were 85%
      Chinese, 9% Malays, and 6% Indians. The mean age at onset of the disease was 60
      +/- 10 years. We found a predominance of males (M:F = 1.5:1) as well as MSA-C
      cases (67%). The most common initial presenting features were parkinsonism and
      cerebellar signs (27% each). Abnormal neuroimaging was seen in 29 patients (91%).
      Autonomic function testing was abnormal in 58% (7/12). The risk for aid-requiring
      walking and wheelchair use at 3 years from onset of the disease was 31% and 17%,
      respectively. By 5 years, this had increased to 45% and 30%, respectively. There
      was no difference in the events rate between MSA subtypes. CONCLUSIONS: The
      clinical characteristics of MSA in Singapore are presented. Our study revealed a
      predominance of MSA-C patients as well as a later age at onset of disease and
      longer median time to aid-requiring walking and wheelchair use compared to
      Japanese patients.

PMID- 16284678
TI  - Neonatal hepatic abscess in preterm infants:a rare entity?
AB  - INTRODUCTION AND OBJECTIVE: Neonatal pyogenic hepatic abscess in preterm infants
      is a rare entity. We present 6 cases of neonatal liver abscesses diagnosed in our
      hospital as well as an approach that will facilitate the early diagnosis and
      management of neonatal pyogenic liver abscess based on our case series and review
      of the literature. MATERIALS AND METHODS: Retrospective review of case records of
      all 6 patients diagnosed with neonatal liver abscess from January 2000 to
      December 2002 in KK Women's and Children's Hospital, Singapore. RESULTS: All
      neonates were premature with gestational ages between 24 and 34 weeks.
      Persistence of positive blood culture despite appropriate antibiotic treatment in
      67% of the cases prompted use of hepatobiliary ultrasounds to detect liver
      abscess. Surgical drainage of liver abscess was performed in 33% of the cases,
      with the remainder treated conservatively with appropriate intravenous
      antibiotics. Half of the infants recovered with resolution of their liver abscess
      on serial hepatobiliary ultrasound. The other half died of fulminant sepsis.
      CONCLUSIONS: Neonatal pyogenic liver abscess, though rare, is associated with
      good outcome if diagnosed promptly and appropriate treatment instituted. In a
      preterm infant with sepsis, a high index of suspicion is required if there is
      persistence of positive blood culture despite appropriate antibiotic treatment,
      and hepatobiliary ultrasound should be done to detect and monitor neonatal liver
      abscess.

PMID- 16284679
TI  - Impetigo herpetiformis--a rare dermatosis of pregnancy associated with prenatal
      complications.
AB  - INTRODUCTION: We describe a patient who developed an acute generalised pustular
      eruption associated with pyrexia at 33 weeks of gestation. CLINICAL PICTURE: Her
      condition was complicated by preterm labour, requiring an emergency caesarean
      section delivery. A diagnosis of impetigo herpetiformis was made on
      clinicopathological grounds. TREATMENT: Initial treatment with topical and
      systemic corticosteroids failed and oral methotrexate was added. OUTCOME: She
      responded well to this therapy and required only 2 doses of weekly methotrexate.
      CONCLUSION: Impetigo herpetiformis is a rare dermatosis of pregnancy that
      requires early recognition and treatment to prevent maternal and fetal morbidity.
      Combination therapy using oral corticosteroids and short-term methotrexate is
      effective.

PMID- 16284680
TI  - Gastric pneumatosis after endoscopic argon plasma coagulation.
AB  - INTRODUCTION: Endoscopic argon plasma coagulation (APC) is gaining widespread
      usage but its risk is underreported. CLINICAL PICTURE: A 74-year-old man who
      received radical radiotherapy for gastric carcinoma 6 months ago was admitted for
      anaemia and maelena. Gastroscopy revealed haemorrhagic radiation gastritis.
      Endoscopic APC was performed but terminated when he complained of severe
      epigastric pain. Computed tomography scan showed gastric pneumatosis. TREATMENT:
      His pain subsided with a period of overnight rest and observation. OUTCOME: He
      continued to have 3 sessions of endoscopic APC at monthly intervals and at 10
      months posttreatment, his haemoglobin remained stable at 11.1 g/dL. CONCLUSIONS:
      This case report highlights a complication of gastric pneumatosis and discusses
      the safe usage of this modality of endoscopic haemostasis. This is to increase
      cognisance of this potentially fatal complication among endoscopists.

PMID- 16284681
TI  - Autosomal dominant familial chronic mucocutaneous candidiasis associated with
      acne rosacea.
AB  - INTRODUCTION: Autosomal dominant chronic mucocutaneous candidiasis (CMC) without
      endocrinopathy (OMIM 114580) is a well-described entity. The associations
      recorded with this disorder to date are intercellular adhesion molecule-1 (ICAM
      1) deficiency and hyper-immunoglobulin E syndrome. CLINICAL PICTURE: We report a
      new association in a family (mother and nonidentical twin sons) where acne
      rosacea is a prominent feature together with CMC. In addition, antibodies to
      thyroid microsomal and antiparietal cell were also isolated. The autoantibodies
      might be associated with a current "latent" endocrinopathy in particular
      autoimmune thyroiditis. TREATMENT: The patient was treated with intermittent
      pulses of itraconazole for the candidiasis and doxycycline initially before being
      substituted with isotretinoin 6 months later for the rosacea. OUTCOME: The
      patient's candidiasis responded well and has been in remission for 3 months while
      his rosacea continues to improve.

PMID- 16284682
TI  - Severe upper limb complications from parenteral abuse of Subutex.
AB  - INTRODUCTION: Subutex is a sublingual formulation of buprenorphine that is used
      to treat opioid dependency. It may be abused parenterally with disastrous
      consequences. CLINICAL PRESENTATION: We present 4 cases of parenteral abuse of
      Subutex resulting in severe upper limb complications. TREATMENT: Two vascular
      complications were treated with combinations of anticoagulants, vasodilators,
      brachial plexus bock and iloprostol. One severe hand abscess required surgical
      debridement, and 1 median nerve injury required neurolysis. OUTCOME: All patients
      had a poor outcome. Both patients with vascular complications required multiple
      amputations, the patient with a thenar abscess had severely impaired thumb
      function, and the patient with median nerve injury has ongoing neuralgic pain,
      numbness and thenar weakness. CONCLUSION: The incidence of complications of
      parenteral abuse of Subutex is increasing in Singapore. These complications have
      a poor outcome despite adequate management, and are best prevented by education
      or legal means.

PMID- 16284683
TI  - Adult-onset re-emergent stuttering as a presentation of Parkinson's disease.
AB  - INTRODUCTION: The basal ganglia-thalamocortical motor circuits are postulated to
      play a key role in the aetiopathogenesis of stuttering. The main dysfunction is
      thought to be an impairment in the ability of the basal ganglia to produce timing
      cues for the initiation of the next motor segment of speech, explaining the
      association of acquired and re-emergent stuttering with diseases such as dystonia
      and Parkinson's disease. CLINICAL PICTURE: We describe a 61-year-old man
      presenting with re-emergent stuttering and mild hypomimia, only to develop
      unilateral rest tremors, hypo- and bradykinesia, rigidity and gait difficulties
      one year later. TREATMENT AND OUTCOME: His parkinsonism responded well to
      treatment with bromocriptine, but he continued to stutter. DISCUSSION: This case
      illustrates the association between acquired or re-emergent stuttering and basal
      ganglia disorders, and highlights the need to assess such patients for an
      underlying aetiology.

PMID- 16284684
TI  - Wound infections in tsunami survivors: a commentary.
AB  - Survivors of the December 2004 Indian Ocean tsunami sustained a variety of wound
      infections, ranging from common pathogens to rarely seen organisms. This article
      discusses the likely microbiology potentially seen in wound infections with
      exposure to freshwater, seawater, soil, faecal or other contamination, and
      attempts to provide an organising framework for choosing empiric antibiotics for
      such infections. Therapy for less frequently encountered clinical entities is
      also discussed, including tetanus, cutaneous and septicaemic melioidosis, post
      traumatic mucormycosis, Vibrio vulnificus and Aeromonas hydrophila.

PMID- 16284685
TI  - Disaster relief and initial response to the earthquake and tsunami in Meulaboh,
      Indonesia.
AB  - The Singapore Humanitarian Assistance Support Group deployed a team of 32 medical
      relief workers to Meulaboh, Indonesia to provide medical assistance for victims
      of the 26 December earthquake and tsunami disaster. The team was deployed at a
      primary healthcare clinic at an internally displaced persons' (IDP) camp and at
      the sole hospital's emergency and surgical departments. The team saw a total of
      1841 patients, 1371 at the clinic and 446 at the hospital's emergency department,
      and performed surgery on 24 patients. Tsunami-related trauma cases accounted for
      31.8% (142) of cases at the emergency department, 1.6% (22) of cases at the
      clinic, and 91.7% (22) of surgeries. This paper details the difficulties and
      lessons learnt by the team, including the lack of important resources for
      healthcare delivery. Water, sanitation, hygiene, and vector control were some of
      the problems faced, with the goal to provide the most effective public health for
      the greatest number of people given the limited resources available.

PMID- 16284686
TI  - Cancer stem cells.
AB  - There is an increasing evidence supporting the cancer stem cell hypothesis.
      Normal stem cells in the adult organism are responsible for tissue renewal and
      repair of aged or damaged tissue. A substantial characteristic of stem cells is
      their ability for self-renewal without loss of proliferation capacity with each
      cell division. The stem cells are immortal, and rather resistant to action of
      drugs. They are able to differentiate and form specific types of tissue due to
      the influence of microenvironmental and some other factors. Stem cells divide
      asymmetrically producing two daughter cells -- one is a new stem cell and the
      second is progenitor cell, which has the ability for differentiation and
      proliferation, but not the capability for self-renewal. Cancer stem cells are in
      many aspects similar to the stem cells. It has been proven that tumor cells are
      heterogeneous comprising rare tumor initiating cells and abundant non-tumor
      initiating cells. Tumor initiating cells -- cancer stem cells have the ability of
      self-renewal and proliferation, are resistant to drugs, and express typical
      markers of stem cells. It is not clear whether cancer stem cells originate from
      normal stem cells in consequence of genetic and epigenetic changes and/or by
      redifferentiation from somatic tumor cells to the stem-like cells. Probably both
      mechanisms are involved in the origin of cancer stem cells. Dysregulation of stem
      cell self-renewal is a likely requirement for the development of cancer.
      Isolation and identification of cancer stem cells in human tumors and in tumor
      cell lines has been successful. To date, the existence of cancer stem cells has
      been proven in acute and chronic myeloid leukemia, in breast cancer, in brain
      tumors, in lung cancer and gastrointestinal tumors. Cancer stem cell model is
      also consistent with some clinical observations. Although standard chemotherapy
      kills most cells in a tumor, cancer stem cells remain viable. Despite the small
      number of such cells, they might be the cause of tumor recurrence, sometimes many
      years after the "successful" treatment of primary tumor. Growth of metastases in
      distinct areas of body and their cellular heterogeneity might be consequence of
      cancer stem cell differentiation and/or dedifferentiation and asymmetric division
      of cancer stem cells. Further characterization of cancer stem cells is needed in
      order to find ways to destroy them, which might contribute significantly to the
      therapeutic management of malignant tumors.

PMID- 16284687
TI  - Anti-apoptotic proteins-targets for chemosensitization of tumor cells and cancer
      treatment.
AB  - Apoptosis or programmed cell death is an essential process not only for the
      normal development and function of multi-cellular organisms but it is also an
      important phenomenon in tumor cells killing. Numerous studies have indicated that
      non surgical cancer therapies eliminate tumor cells by activating apoptosis. The
      central regulators of apoptosis are proteins of the Bcl-2 family. In a wide
      variety of human tumors, the increased expression of anti-apoptotic proteins (Bcl
      2 and Bcl-(XL)) was found. Moreover, it was revealed that high levels of these
      proteins block the action of many chemotherapeutic drugs. Due to this fact the
      inhibition of anti-apoptotic function of Bcl-2 proteins could be a strategy for
      either to restore the normal apoptotic process in tumor cells or to make them
      susceptible for chemo- and radio-therapeutic treatment. Three alternative
      therapeutic strategies for the repression of cytoprotective activity of anti
      apoptotic proteins in tumor cells are reviewed in this article.

PMID- 16284688
TI  - Structure-activity relationship of trans-resveratrol and its analogues.
AB  - Cancer is one of the main causes of death in both men and women, claiming over 6
      million people each year worldwide. Chemoprevention in combination with anti
      cancer treatment is therefore important to reduce morbidity and mortality.
      Stilbene-based compounds have over the years attracted attention of many
      researchers due to their wide ranging biological activities. One of the most
      relevant and extensively studied stilbenes is trans-resveratrol, a phytoalexin
      present in grapes and other foods. One of the most striking biological activities
      of trans-resveratrol soundly investigated during recent years has been its cancer
      chemopreventive potential. It has been found that the biological activity of
      trans-resveratrol and its analogues depends significantly on the structural
      determinants, which are (i) number and position of hydroxyl groups, (ii)
      intramolecular hydrogen bonding, (iii) stereoisomery and (iv) double bond. The
      observation that trans-stilbene compounds having 4 -hydroxy group, double bond
      and bearing ortho-diphenoxyl or para-diphenoxyl functionalities possess
      remarkably higher chemopreventive activity than trans-resveratrol gives us useful
      information for further chemopreventive drug design.

PMID- 16284689
TI  - High-dose methotrexate and/or leucovorin rescue for the treatment of children
      with lymphoblastic malignancies: do we really know why, when and how?
AB  - Methotrexate (MTX) remains a mainstay in the treatment of children with
      hematological malignancies. The availability of an antidote/rescue agent,
      leucovorin (LV) has allowed escalation of MTX doses to achieve enormous plasma
      concentrations, compared with plasma folate. However, a recent review of more
      than 40 trials for children with ALL concluded that the addition of high dose MTX
      (HDMTX) in many different doses and schedules did not improve CNS therapy and
      made only minor improvements in systemic therapy for children with ALL [11]. Some
      assessment suggested that by HDMTX benefits only limited amount of children with
      ALL. Recent treatment schedules vary markedly in terms of timing, dosing and
      scheduling of MTX and/or leukovorin, which may leave us uncertain with ideas such
      as "how should we best use HDMTX and LV?" or "why are we still using such by
      industry recommended doses of MTX?" The answer of how best to incorporate HDMTX
      and/or LV into ALL treatment plans is still not known and further clinical and
      pharmacological studies dealing with still controversial systemic MTX issue are
      actual even now, after more than 5 decades of clinical experiences with the MTX
      in pediatric oncology.

PMID- 16284690
TI  - Expression of the P65 gene in gastric cancer and in tissues with or without
      Helicobacter pylori infection.
AB  - A 65-kDa tumor-associated protein (P65) is a potential non- specific tumor marker
      expressed by many types of tumor cells. Our recent studies indicate that P65 gene
      expression is connected with poor prognosis for the patients with colorectal
      cancer. In the present study P65 gene expression was determined by means of RT
      PCR in the group of 22 gastric cancer and adjacent normal gastric mucosa. Its
      presence was correlated with some parameters of clinical staging. P65 gene
      expression was also determined in 102 tissue antral gastric endoscopic biopsy
      specimens from the patients suspected of H. pylori infection. The presence of H.
      pylori infection was determined by urease test. We found that in the group of
      gastric cancers, similarly to colorectal cancer, P65 gene expression was
      connected with poor clinicopathological parameters as T3, lymph nodes and distant
      metastases. There was no dependence between P65 gene expression and H. pylori
      infection. However, more often P65 gene expression was detected in the group of
      infected men than women. There was also a statistically significant dependence
      between age and P65 gene expression in the group of people above 60 years old. It
      could be then postulated that P65 gene expression is connected with poor
      prognosis for the patients suffering from gastric cancer and that this expression
      does not depend on H. pylori infection.

PMID- 16284691
TI  - Comparative assessment of the cytotoxic effects of carboxylato-bridged dinuclear
      platinum (II) complexes against human tumor cell lines.
AB  - The cytotoxic effects of a series of carboxylato-bridged dinuclear platinum (II)
      complexes with acetate (BAP), propionate (BPP) and valerate (BVP) ligands were
      evaluated in a panel of human tumor cell lines. BAP proved to be the most potent
      antineoplastic agent, whose cytotoxic effect reached and even outclassed that of
      the referent drug cisplatin. This compound also exerted substantial efficacy
      against a broader spectrum of tumor models including the multidrug-resistant HL
      60/Dox cell line. In the latter case, BAP showed lower resistance index than
      cisplatin. BAP was furthermore found to induce apoptosis in different cell lines
      as evidenced by DNA-laddering and Cell-death ELISA. Our experimental data give us
      reason to conclude that the dinuclear Pt(II) complex with acetate ligands is
      perspective for further detailed pharmacological and toxicological evaluation as
      an antineoplastic drug candidate.

PMID- 16284692
TI  - A randomized, double blind comparative study of prophylactic parenteral
      nutritional support with or without glutamine in autologous stem cell
      transplantation for hematological malignancies -- three years' follow-up.
AB  - Forty-four adult autologous transplant patients with hematological malignancies
      were randomized to receive either prophylactic parenteral nutrition PN (P group),
      or PN given ad hoc (C group). In each group, they were further randomized to
      receive standard PN (B group), or PN with 0.5 g glutamine/kg as L-Ala-L-Gln (A
      group). The overall survival (OS), disease-free survival (DFS) and event-free
      survival (EFS) in groups C vs. P and A vs. B were compared during follow-up with
      median 38 months. The final outcome rates in C/P/A/B groups, respectively (OS
      65/81/63/85%, EFS 45/53/33/65% and DFS 56/50/35/77%), were not significantly
      different, apart from A < B in DFS rate (p=0.03, Fisher's exact test). Also in
      survival analysis (logrank test), no significant difference between groups C and
      P was found but generally worse parameters were observed for A vs. B group: for
      DFS (p=0.04) and EFS (p=0.01) the difference was significant, and for OS (p=0.09)
      it was borderline. In the three years' follow-up, no clinically useful benefit of
      prophylactic PN in autologous transplant patients was proven. Also, glutamine
      supplementation was not helpful, and was even connected with apparently worse
      long-term outcome.

PMID- 16284693
TI  - Predictors of local failure in early laryngeal cancer.
AB  - The aim of the study was to assess the impact of factors that could predict the
      probability of local failure in early laryngeal squamous cell carcinoma treated
      with curative radiotherapy. Sixty seven patients (12 women and 55 men) with
      laryngeal cancer stage I (47 patients) and stage II (20 patients) were treated
      from 1998 to 2003 with curative radiotherapy and retrospectively evaluated.
      Median follow-up was 36 months (3-80). Local relapse occurred in 10 patients
      (15%), regional lymphnodes relapse affected 2 patients. The median time between
      start of radiotherapy to recurrence was 13 months (3-48). Death due to cancer
      occurred in 4 patients (2 died from locoregional progression of the recurrence
      and 2 from distant metastases), whereas 7 patients died from non-cancer related
      causes. The 2-year overall survival rate was 90% and 5-year OS was 79%. The 2
      year local control rate was 82% and 5-year local control was 79%. In the
      univariate analysis there was a statistically significant decrease in local
      control influenced by grading (p < 0.0001). High risk group of relapse
      encompassed patients with at least two negative factors: supraglottic tumor,
      women, radiotherapy prolongation by 3 or more days and high grade tumor and has 3
      times worse local control than low risk group (p=0.0125). The highest risk of
      local recurrence was in the first three years after radiotherapy than later
      (p=0.0057). On multivariate analysis unfavourable prognostic factors for local
      control were gender (p=0.022), presence of 2 or more negative risk factors
      (p=0.018) and lengths of follow up (p=0.005). Radiation dose, stage, age,
      hemoglobin level and anterior commissure involvement were not significant factors
      for local control. Overall survival was affected both in the univariate and
      multivariate analysis by presence of local relapse (p < 0.005) and follow up
      duration (p < 0.02). Anemia had borderline significance for overall survival in
      univariate analysis (p=0.064), but in the multivariate analysis was significant
      unfavourable factor (p=0.008). Other studied factors (radiation dose, anterior
      commissure involvement and age) were not reaching level of statistical
      significant value for overall survival. Close follow up strategy is recommended
      for high risk group of patients with two or more risk factors especially in the
      first three years after radiation therapy.

PMID- 16284694
TI  - The effect of doxorubicin on the expression of cyclin A in K-562 leukemia cell
      line.
AB  - Two opposite processes such as apoptosis and cell division cycle play an
      important role in cancer biology. During apoptosis cells die by degrading
      proteins and genome, whereas in the cell cycle cells divide and the genome is
      duplicated. There are very few studies on the role of cell cycle proteins in
      apoptosis although their role is distinctly different from that in the cell
      cycle. The significance of expression of cyclin A and other cyclin cell proteins
      (eg. Cdk2) in apoptosis remains to be investigated. The aim of this study was to
      characterize the distribution pattern of cyclin A by using the stereptavidin -
      biotin - peroxidase technique in K-562 cells treated with doxorubicin. The
      analysis of cell cycle phases using cytophotometric methods to estimate the
      cellular response to doxorubicin was also used. Studied cells were treated with
      doxorubicin in the range 0.5; 5.0 and 10 microM. Expression of cyclin A in K-562
      was 32.2; 41.8; 69.9%, respectively, according to doses of doxorubicin. The
      number of apoptotic cells was increasing together with the increase of
      doxorubicin doses as well as positive labeling for cyclin A. After doxorubicin
      treatment decrease of G1/G0 phase and the growth of cell percentage with dose
      dependent manner at G2/M phase, compared to control was observed. The results
      allow to suggest that expression of cyclin A may have pro-apoptotic role however
      more studies are required to clarify whether and what role cyclin A plays in
      apoptosis.

PMID- 16284695
TI  - Evaluation of treatment results and toxicity in cases of repeated radiation
      therapy of spinal metastasis.
AB  - The study evaluates retrospective results and toxicity in repeated radiation
      therapy in patients with recurrent pain caused by backbone metastasis, having
      undergone previous radiotherapy in the same body region. Fifty-seven patients
      were analyzed: 24 women and 33 men, aged 45-74 years (median = 59 years). They
      underwent a second radiation therapy treatment of the spinal column, between
      March 2002 and May 2004, performed due to recurrent pain in the previously
      irradiated region. The radiation used cobalt isotope 60 ((60)Co), to include the
      metastatically changed vertebrae and the margin of the adjusting healthy upper
      and lower vertebra. The radiated skin area measured 84-104 cm(2). Patients were
      divided into 3 groups depending on their treatment schemas: 12 patients -- first
      course of radiotherapy 4 Gy x 5, second 4 Gy x 5; 16 patients -- first course of
      radiotherapy 4 Gy x 5, second 8 Gy x 1; 29 patients -- first course of
      radiotherapy 8 Gy x 1, second 8 Gy x 1. The time delay between the first and the
      second radiation therapies was between 11 and 766 days (median = 135 days). An
      analgesic effect was achieved with most treated patients -- 41/57 (71.9%) with
      the use of second radiotherapy and with an insignificant percentage of
      complications, unimportant from the clinical point of view. No serious
      complications such as paralysis, paresis, spinal cord necrosis, neurological
      dysfunction of urethral or sigmoidorectal sphincters were noted in any of the
      treated patients. Based on our experience, this retrospective analysis shows
      usefulness of the second radiotherapy treatment as a safe method of palliative
      treatment in cases of painful bone metastasis appearing after a previous
      radiation therapy.

PMID- 16284696
TI  - Paclitaxel plus ifosfamide and cisplatin in second-line treatment of germ cell
      tumors: a phase II study.
AB  - The aim of this study was to determine efficacy and toxicity of TIP combination
      (paclitaxel, ifosfamid, cisplatin) as first salvage treatment in patients with
      relapsed germ cell tumours (GCTs). Excellent results were achieved from TIP
      combination with a dose 250 mg/m(2) of paclitaxel [5]. Our hypothesis was that
      comparable efficacy with less toxicity could be achieved even with a lower dose
      of 175 mg/m(2) paclitaxel in TIP. In 17 consecutive patients with failed standard
      1st line treatment, we used four to six courses of paclitaxel 175 mg/m(2) on day
      1 and ifosfamide 1,200 mg/m(2) plus cisplatin 20 mg/m(2), both on day 1 through
      5, every 3 weeks. Eleven patients achieved favorable response (65%; 95%
      confidence interval, 42 to 87%) with 7 complete responses (41%). Estimated 2-year
      disease free survival is 47% (95% CI, 23-71%). Treatment combination was well
      tolerated and myelosupression was major toxicity. Granulocytopenia Gr3-4 was
      observed in 8% and febrile neutropenia in 7% of the courses. No case of severe
      neurotoxicity or treatment-related death was observed. In our study, TIP
      combination had good toxicity profile. The results however, did not show expected
      treatment efficacy and we raise the idea of paclitaxel dosage relevance in TIP.

PMID- 16284697
TI  - The knowledge on the 3rd type hematogones could contribute to more precise
      detection of small numbers of precursor B-acute lymphoblastic leukemia.
AB  - Bone marrow hematogones (benign B-lymphocyte precursors) may cause diagnostic
      problems due to their morphologic and immunophenotypic similarities with
      neoplastic lymphoblasts. Hematogone populations in presented study containing 358
      bone marrow specimens of 251 individuals always exhibited a continuous and
      complete maturation spectrum of antigen expression typical for normal evolution
      of B-lineage precursors; lacking aberrant or asynchronous antigen expression. In
      contrast lymphoblasts of 19 bone marrows of precursors B-ALL patients showed
      maturation arrest and exhibited several immunophenotypic aberrancies. Hematogones
      were identified by 4-color flow cytometry using optimal antibody combinations in
      many bone marrow samples. They were more commonly found in higher numbers in
      children, and there was found a general decline in hematogones with increasing
      age. Bone marrow hematogones were separately assessed as hematogones 1 population
      of early stage and hematogones 2 of mid-stage precursor B-cells, respectively. In
      some (about 30%) of hematogones a third type hematogones could be assessed in
      bone marrow samples. This small B-cell subpopulation was defined by CD10
      positivity, coexpressing more mature markers CD19,CD20,CD22 and CD45bright. These
      cells obviously blended with those of mature B-lymphocytes (CD10-negative) on
      CD45/SSC, and could be better recognized on CD10-gating. Quantitative
      immunophenotyping of this study completed the percent antigen expression data in
      two main hematogone subtypes and lymphocytes in 16 bone marrow specimens and
      precursor B-ALL lymphoblasts in some samples. Increased information on benign B
      lymphocyte precursors, especially that of existence of the 3rd type hematogones
      could provide a basis for better discrimination of B-leukemia cells even in a
      very small amounts.

PMID- 16284698
TI  - Enhanced sensitivity of human ovarian carcinoma cell lines A2780 and A2780/CP to
      the combination of cisplatin and synthetic isothiocyanate ethyl 4
      isothiocyanatobutanoate.
AB  - Naturally occurring and synthetic isothiocyanates (ITCs) are known as
      chemopreventive agents. The present study shows a new synthetic ITC derivate
      ethyl 4-isothiocyanatobutanoate (E-4IB) as an effective modulator of cellular
      proliferation and inducer of apoptosis with potential utility as an anticancer
      drug, as well as a sensitizer to routinely used chemotherapeutic agent cisplatin
      (cis-Pt). Evaluation of the growth inhibitory effects of E-4IB in the human
      ovarian carcinoma cell line A2780 and its cisplatin-resistant variant A2780/CP
      using MTT-test and its apoptosis-inducing properties by flow cytometry was
      performed. Effect of E-4IB was assessed both alone and in paired combination with
      cisplatin. Combination index (CI) values from Calcusyn software were used to
      characterize the interactions as synergistic, additive, or antagonistic.
      Significant synergistic effect in growth inhibition of E-4IB (0.5-5 microM) with
      cis-Pt (2.5-10 microM) on A2780 parental cell line (CI from 0.39 to 0.75) was
      also observed on A2780/CP resistant subline, although to a lesser extent (CI from
      0.43 to 0.86) for cis-Pt concentrations 5-25 microM and the same concentrations
      of E-4IB. Synergy in growth inhibition correlated with the potential of E-4IB to
      stimulate apoptosis induced by cis-Pt (from 9.5% to 24.7% at 24 hours) while E
      4IB alone induced 3.6% of apoptotic cells in A2780 cell line. We conclude that E
      4IB may be worth of further studies assessing its value in the ovarian carcinoma
      treatment, in combination with the other chemotherapeutic agents.

PMID- 16284699
TI  - The value of dot plot patterns and leukemia-associated phenotypes in AML
      diagnosis by multiparameter flow cytometry.
AB  - The immunophenotypic features in patients with acute myeloid leukemia (AML) were
      investigated at diagnosis using a wide antibody panel including progenitor
      associated, myeloid and lymphoid markers in quadruple combinations. Analyzed were
      bone marrow samples from 37 adult and pediatric patients for exact identification
      of AML blasts according their localization on CD45/SSC dot plots and aberrant
      immunophenotypes in various subtype of AML. We found the localization of AML
      blasts on CD45/SSC dot plots, which in combination with immunophenotype profile
      of blasts allow discrimination of several AML subtypes (M0-M2, M3, M4/M5 and
      other types). In 27/37 AML patients (73%) at least one leukemia-associated
      phenotype (LAP) was found, two or more aberrancies coexisted in more than a half
      of them (78%). Asynchronous expression was the most frequent type of LAP (77.8%,
      21/27) followed by coexpression of lymphoid-associated antigens, which occurred
      in 18/27 (66.7%) patients. Presented study showed that leukemic cells of each AML
      patient had a unique antigenic profile and could be discriminated from their
      normal counterparts based on typical light scatter profiles and aberrant antigen
      expression that could further be used for detection of minimal residual disease.

PMID- 16284700
TI  - Fate of the inguinal hernia following removal of infected prosthetic mesh.
AB  - Open tension-free hernioplasty using a prosthetic mesh is a common operation for
      inguinal hernia repair because of the relative ease of the operation and low
      recurrence rate. Wound infection is a potential complication of all hernia
      repairs and deep-seated infection involving an inserted mesh may result in
      chronic groin sepsis which usually necessitates complete removal of mesh to
      produce resolution. Removal of mesh would potentially result in a weakness of the
      repair and subsequent hernia recurrence. We reviewed the outcome of all our
      patients who had mesh removal for sepsis over an 8-year period, particularly
      examining for hernia recurrence and chronic groin pain. This was a retrospective
      review of the database of patients who had mesh repair of inguinal hernias over
      an 8-year period. There were 2,139 inguinal hernias repaired using prosthetic
      mesh. All patients who had mesh removal for infection were identified and
      followed up. Fourteen patients had deep-seated wound infection which required
      mesh removal for resolution of sepsis. No peri-operative complications occurred
      during mesh removal. After a median follow-up of 44 months (range 5-91 months),
      there were two asymptomatic recurrences and none of the patients had chronic
      groin pain. Hernia recurrence is uncommon following mesh removal for chronic
      groin sepsis, suggesting that the strength of a mesh repair lies in the fibrous
      reaction evoked within the transversalis fascia by the prosthetic material rather
      than in the physical presence of the mesh itself. When there is established deep
      infection, there should be no unnecessary delay in removing an infected mesh in
      order to allow resolution of chronic groin sepsis.

PMID- 16284701
TI  - Percutaneous transcatheter one-step mechanical aortic disc valve prosthesis
      implantation: a preliminary feasibility study in swine.
AB  - PURPOSE: To evaluate the feasibility of one-step implantation of a new type of
      stent-based mechanical aortic disc valve prosthesis (MADVP) above and across the
      native aortic valve and its short-term function in swine with both functional and
      dysfunctional native valves. METHODS: The MADVP consisted of a folding disc valve
      made of silicone elastomer attached to either a nitinol Z-stent (Z model) or a
      nitinol cross-braided stent (SX model). Implantation of 10 MADVPs (6 Z and 4 SX
      models) was attempted in 10 swine: 4 (2 Z and 2 SX models) with a functional
      native valve and 6 (4 Z and 2 SX models) with aortic regurgitation induced either
      by intentional valve injury or by MADVP placement across the native valve. MADVP
      function was observed for up to 3 hr after implantation. RESULTS: MADVP
      implantation was successful in 9 swine. One animal died of induced massive
      regurgitation prior to implantation. Four MADVPs implanted above functioning
      native valves exhibited good function. In 5 swine with regurgitation, MADVP
      implantation corrected the induced native valve dysfunction and the device's
      continuous good function was observed in 4 animals. One MADVP (SX model) placed
      across native valve gradually migrated into the left ventricle. CONCLUSION: The
      tested MADVP can be implanted above and across the native valve in a one-step
      procedure and can replace the function of the regurgitating native valve. Further
      technical development and testing are warranted, preferably with a manufactured
      MADVP.

PMID- 16284702
TI  - Usefulness of transjugular intrahepatic portosystemic shunt in the management of
      bleeding ectopic varices in cirrhotic patients.
AB  - PURPOSE: To evaluate the safety and efficacy of transjugular intrahepatic
      portosystemic shunt (TIPS) in the control of bleeding from ectopic varices.
      METHODS: From 1995 to 2004, 24 cirrhotic patients, bleeding from ectopic varices,
      mean age 54.5 years (range 15-76 years), were treated by TIPS. The etiology of
      cirrhosis was alcoholic in 13 patients and nonalcoholic in 11 patients. The
      location of the varices was duodenal (n = 5), stomal (n = 8), ileocolic (n = 6),
      anorectal (n = 3), umbilical (n = 1), and peritoneal (n = 1). RESULTS: TIPS
      controlled the bleeding in all patients and induced a decrease in the portacaval
      gradient from 19.7 +/- 5.4 to 6.4 +/- 3.1 mmHg. Postoperative complications
      included self-limited intra-abdominal bleeding (n = 2), self-limited hemobilia (n
      = 1), acute thrombosis of the shunt (n = 1), and bile leak treated by a covered
      stent (n = 1). Median follow-up was 592 days (range 28-2482 days). Rebleeding
      occurred in 6 patients. In 2 cases rebleeding was observed despite a post-TIPS
      portacaval gradient lower than 12 mmHg and was controlled by variceal
      embolization; 1 patient underwent surgical portacaval shunt and never rebled; in
      3 patients rebleeding was related to TIPS stenosis and treated with shunt
      dilatation with addition of a new stent. The cumulative rate of rebleeding was
      23% and 31% at 1 and 2 years, respectively. One- and 2-year survival rates were
      80% and 76%, respectively. CONCLUSION: The present series demonstrates that
      bleeding from ectopic varices, a challenging clinical problem, can be managed
      safely by TIPS placement with low rebleeding and good survival rates.

PMID- 16284703
TI  - Interventions in infrainguinal bypass grafts.
AB  - The interventional radiologist plays an important role in the detection and
      prevention of infrainguinal bypass failure. Early detection and evaluation of
      flow-limiting lesions effectively preserve graft (venous bypass and polyester or
      expanded polytetrafluoroethylene bypass) patency by identifying stenoses before
      occlusion occurs. Delay in treatment of the at-risk graft may result in graft
      failure and a reduced chance of successful revascularization. For this reason,
      surveillance protocols form an important part of follow-up after infrainguinal
      bypass surgery. As well as having an understanding of the application of imaging
      techniques including ultrasound, MR angiography, CT angiography and digital
      subtraction angiography, the interventional radiologist should have detailed
      knowledge of the minimally invasive therapeutic options. Percutaneous
      transluminal angioplasty (PTA), or alternatively cutting balloon angioplasty, is
      the interventional treatment of choice in prevention of graft failure and
      occlusion. Further alternatives include metallic stent placement, fibrinolysis,
      and mechanical thrombectomy. Primary assisted patency rates following PTA can be
      up to 65% at 5 years. When the endovascular approach is unsuccessful, these
      therapeutic options are complemented by surgical procedures including vein patch
      revision, jump grafting, or placement of a new graft.

PMID- 16284705
TI  - Efficacy of bilateral subthalamic nucleus (STN) stimulation in Parkinson's
      disease.
AB  - BACKGROUND: Deep brain stimulation (DBS) has, for the most part, replaced
      irreversible stereotactic coagulations in the surgical treatment of advanced
      Parkinson's disease. This study was undertaken to evaluate the benefits of
      bilateral STN stimulation related to its potential risks and side effects.
      METHOD: Twenty-nine consecutive Parkinsonian patients treated with STN-DBS were
      prospectively followed-up. Effects on Parkinsonian symptoms were evaluated using
      the Unified Parkinson's Disease Rating Scale (UPDRS). The evaluation was
      performed preoperatively and included postoperative follow-up evaluations at one
      and twelve months. All evaluations were made during the patient's best on
      medication phase and postoperative follow-ups were conducted under both
      stimulator-on and stimulator-off conditions by a blinded neurologist. A
      neuropsychologist also evaluated the patients at every visit. FINDINGS: Two
      patients were excluded from the analysis because of severe surgical complications
      and three for an infection demanding the removal of the stimulator material.
      Other complications and side effects were clearly milder and temporary. At twelve
      months after surgery dyskinesia scores in the UPDRS were 53% lower than
      preoperative values. The results of the UPDRS motor scores improved 31.4% and
      activities of daily living (ADL) scores increased 19% compared with the
      preoperative situation. Also, the daily levodopa dose was 22% lower.
      Neuropsychological changes were minor, except for some deterioration in verbal
      fluency. CONCLUSION: The majority of Parkinsonian patients experienced
      significant and long lasting relief from their motor symptoms and an improvement
      in ADL functions due to DBS-STN therapy when evaluated at the best on-medication
      phase.

PMID- 16284706
TI  - Intracranial pressure parameters in idiopathic normal pressure hydrocephalus
      patients treated with ventriculo-peritoneal shunts.
AB  - BACKGROUND: Although the mean intracranial pressure (ICP) is normal in patients
      with idiopathic normal pressure hydrocephalus (iNPH), there could possibly be
      alterations in their single ICP waves. METHOD: Thirty-nine consecutive patients
      treated for iNPH with ventriculo-peritoneal shunts were followed prospectively
      with regard to clinical and radiological findings. Changes in clinical state 12
      months after shunt surgery were assessed as change on a 15-3 score NPH Grading
      Scale, while the changes in ventricular size were assessed by linear measures.
      The ICP recordings were performed as part of routine pre-operative assessment,
      stored as raw data files, and analyzed retrospectively. The mean ICP as well as
      single ICP wave amplitudes were computed and analysed in consecutive 6 second
      time windows. FINDINGS: Twelve months after shunt surgery, changes in NPH score
      of 5 or more (very significant improvement) were observed in 12 patients (31%),
      of 3 to 4 (significant improvement) in 6 patients (15%), of 1 to 2 (slight
      improvement) in 9 patients (23%) and of -4 to 0 (non-responders) in 12 patients
      (31%). The ventricular size did not change in any of the outcome categories.
      While the pre-operative mean ICP was similar between outcome groups, the mean ICP
      wave amplitude was significantly higher in patients improving clinically as
      compared to the non-responders. CONCLUSIONS: While pre-operative mean ICP was
      similar, the mean ICP wave amplitudes were significantly higher in iNPH patients
      improving clinically after shunt treatment as compared to the non-responders.

PMID- 16284704
TI  - Uptake of a fluorescent deoxyglucose analog (2-NBDG) in tumor cells.
AB  - PURPOSE: A new fluorescent analog of D -glucose was recently developed by
      [Yoshioka K, Takahashi H, Homma T, Sato M, Ki Bong O, Nemoto Y, Matsuoka H (1996)
      A novel fluorescent derivative of glucose applicable to the assessment of glucose
      uptake activity of Escherichia coli. Biochim Biophys Acta 1289:5-9] and shown to
      be transported into normal cells. The purpose of this preliminary study was to
      assess the use of this fluorescent 2-deoxyglucose analog, 2-[N-(7-nitrobenz-2-oxa
      1,3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG), as a sensitive probe for
      monitoring glucose uptake into malignant tumor cells. PROCEDURES: MCF-7 breast
      cancer epithelial cells were grown and plated on coverslips for analysis of 2
      NBDG uptake via fluorescence imaging microscopy. RESULTS: Steady-state
      fluorescence analysis of 2-NBDG uptake displayed rapid uptake for the first one
      to five minutes, then slowed, reaching an apparent maximum uptake near 20-30
      minutes. Addition of 5 mM D -glucose to the media markedly reduced 2-NBDG uptake.
      Uptake of 2-NBDG in nonmalignant epithelial cells (M-1 epithelial cells) was
      slow, averaging less than 20% of that observed for tumorigenic cells, the MCF-7
      breast cancer cells and the HepG2 liver cancer cell line. CONCLUSIONS: The
      preliminary data clearly demonstrate a rapid uptake of 2-NBDG into tumor cells
      that can be monitored by fluorescence imaging analysis. The uptake displays
      saturation and competition with D -glucose, all properties expected for 2-NBDG
      uptake and retention in cancer cells. Additional studies, including comparisons
      among other malignant cell lines and control cells, will be needed to fully
      characterize the kinetic properties of 2-NBDG uptake and the potential use of
      this 2-DG analog as a probe for glucose uptake in malignant cells.

PMID- 16284707
TI  - Microsatellite variation and differentiation among local populations of
      Castanopsis species in Japan.
AB  - Microsatellite variations in Castanopsis species in Japan were examined to
      clarify the genetic relationships among 25 local populations according to the
      difference in the number of layers of adaxial epidermis in the leaves. Six
      microsatellite loci were assayed for 629 seedlings from the populations, and
      these seedlings were classified into five types according to the state of the
      leaf epidermis. Remarkable differences in the allele frequency of the six
      microsatellite loci were observed among these local populations. The coefficients
      of genetic differentiation, R(ST), of each locus ranged from 0.209 to 0.388. An
      unweighted pair-group method (UPGMA) phenogram constructed on the population
      pairwise R(ST) over the loci revealed three clusters (A-C), and six sub-clusters.
      These clusters reflected the differences in the occurrence frequency of seedlings
      in each epidermis type within a population. Our findings suggest that clusters A
      and C are the local populations dominated by Castanopsis sieboldii and
      Castanopsis cuspidata, respectively, while local populations of cluster B are
      composed of the two Castanopsis species and/or include many individuals derived
      by hybridization. The six sub-clusters were found to reflect the geographic
      relationship among the populations, suggesting a different process for geographic
      population dynamics during the postglacial period.

PMID- 16284708
TI  - Establishing and maintaining axial growth: wall mechanical properties and the
      cytoskeleton.
AB  - Organ morphology depends on cell placement and directional cell expansion.
      Microtubules are involved in both of these processes so genetic approaches to
      understand the role microtubules play in organ expansion are not straightforward.
      Our use of the temperature-sensitive mor1-1 mutants led to the surprising
      discovery that Arabidopsis thaliana (L.) Heynh. root cells can establish and
      maintain transverse cellulose texture without well organized microtubule arrays.
      This work also demonstrated that cells can lose the ability to expand
      anisotropically without losing transversely oriented cellulose microfibrils. We
      suggest that microtubule disruption affects the cell's ability to generate long
      cellulose microfibrils, which may be essential for achieving growth anisotropy.
      Thus organ shape may depend not only on the orientation but also on the relative
      length of cellulose microfibrils during axis establishment and growth. More
      recent work has shown an important correlation between microtubule organization
      and the deposition patterns of the glycosylphosphatidylinositol (GPI)-anchored
      wall protein COBRA. Loss of microtubule organization is associated with the
      dissipation of transverse banding patterns of COBRA, suggesting that COBRA's
      function in maintaining anisotropic expansion may be microtubule-dependent.

PMID- 16284709
TI  - Coordination of cell proliferation and cell expansion in the control of leaf size
      in Arabidopsis thaliana.
AB  - Size is an important parameter in the characterization of organ morphology and
      function. To understand the mechanisms that control leaf size, we previously
      isolated a number of Arabidopsis thaliana mutants with altered leaf size. Because
      leaf morphogenesis depends on determinate cell proliferation, the size of a
      mature leaf is controlled by variation in cell size and number. Therefore, leaf
      size mutants should be classified according to the effects of the mutations on
      the cell number and/or size. A group of mutants represented by angustifolia3/grf
      interacting factor1 and aintegumenta exhibits an intriguing cellular phenotype
      termed compensation: when the leaf cell number is decreased due to the mutation,
      the leaf cell size increases, leading to compensation in leaf area. Several lines
      of genetic evidence suggest that compensation is probably not a result of the
      uncoupling of cell division from cell growth. Rather, the evidence suggests an
      organ-wide mechanism that coordinates cell proliferation with cell expansion
      during leaf development. Our results provide a key, novel concept that explains
      how leaf size is controlled at the organ level.

PMID- 16284710
TI  - A multicentered comparison of measurements obtained with microtip and external
      water pressure transducers.
AB  - This study compared simultaneous intravesical pressure readings obtained with
      catheter-mounted microtip transducers and external water pressure transducer
      catheters during filling cystometry. Women undergoing multichannel urodynamic
      testing were randomly assigned to one of three groups: two microtip catheters,
      two external water pressure transducer catheters, or one of each type.
      Intravesical pressure was measured simultaneously for each transducer combination
      in each subject for minimal and maximal Valsalva effort and minimal, moderate,
      and maximal cough effort at two sequential bladder volumes (150 and 300 ml).
      Paired t tests were used to compare the means of the intravesical pressure
      obtained by the two types of catheters. The largest mean differences were
      observed when comparing microtip and water pressure transducers. Correlations of
      maximum pressure were consistently high between two microtip transducers and two
      water pressure transducers but lower for the microtip-water combination.
      Excellent reproducibility was demonstrated with transducers of similar types for
      intravesical pressures recorded during Valsalva and cough in women without
      prolapse. However, considerable variability was seen in pressures recorded by
      different transducers, particularly dependent on the water catheter manufacturer,
      indicating that intravesical pressure recordings from microtip and water-based
      systems are not interchangeable.

PMID- 16284711
TI  - Reduced model and simulation of neuron with passive dendritic cable: an
      eigenfunction expansion approach.
AB  - The neuron models with passive dendritic cables are often used for detailed
      cortical network simulations (Protopapas et al., 1998; Suarez et al., 1995). For
      this, the compartment model based on finite volume or finite difference
      discretization was used. In this paper, we propose an eigenfunction expansion
      approach combined with singular perturbation and demonstrate that the proposed
      scheme can achieve an order of magnitude accuracy improvement with the same
      number of equations. Moreover, it is also shown that the proposed scheme
      converges much faster to attain a given accuracy. Hence, for a network simulation
      of the neurons with passive dendritic cables, the proposed scheme can be an
      attractive alternative to the compartment model, that leads to a low order model
      with much higher accuracy or that converges faster for a given accuracy.

PMID- 16284712
TI  - Two cortical circuits control propagating waves in visual cortex.
AB  - Visual stimuli produce waves of activity that propagate across the visual cortex
      of fresh water turtles. This study used a large-scale model of the cortex to
      examine the roles of specific types of cortical neurons in controlling the
      formation, speed and duration of these waves. The waves were divided into three
      components: initial depolarizations, primary propagating waves and secondary
      waves. The maximal conductances of each receptor type postsynaptic to each
      population of neurons in the model was systematically varied and the speed of
      primary waves, durations of primary waves and total wave durations were measured.
      The analyses indicate that wave formation and speed are controlled principally by
      feedforward excitation and inhibition, while wave duration is controlled
      principally by recurrent excitation and feedback inhibition.

PMID- 16284714
TI  - Dopa-responsive hemiparkinsonism due to midbrain Virchow-Robin spaces?

PMID- 16284713
TI  - Striatal dopamine transporter availability is associated with the productive
      psychotic state in first episode, drug-naive schizophrenic patients.
AB  - OBJECTIVE: Supposing a "hyperdopaminergic State" associated at least with acute
      psychotic illness phases in schizophrenia, a direct relationship between striatal
      dopamine metabolism and the core psychopathological symptoms rarely can be
      provided. Recently, a new SPECT ligand to the presynaptic dopamine transporter
      (DAT) was introduced. Association of DAT availability and the acute psychotic
      syndrome is now demonstrated in a large cohort of first episode, never treated
      schizophrenic patients. METHODS: Twenty-eight inpatients suffering from a first
      acute exacerbation of schizophrenia and 12 healthy control subjects underwent
      SPECT scanning with the new radioligand [(99m)Tc]TRODAT-1. On the day of SPECT,
      psychopathology was assessed using specific scales including PANSS. RESULTS:
      There was no significant difference in [(99m)Tc]TRODAT-1 specific binding to the
      striatal DAT comparing both groups. The extend of hallucinations was
      significantly inversely correlated with DAT availability in patients with a
      predominantly positive syndrome type. DISCUSSION: Our data support evidence that
      differences in presynaptic dopaminergic activity in schizophrenic patients are
      associated with the extend of the acute psychotic syndrome. [(99m)Tc]TRODAT-1
      seems to be a useful agent for in vivo assessment of a psychopathological
      association with dopamine metabolism.

PMID- 16284719
TI  - Isolation of Pythium oligandrum from Egyptian soil and its mycoparasitic effect
      on Pythium ultimum var. ultimum the damping-off organism of wheat.
AB  - Pythium oligandrum Drechsler bearing spherical sporangia with complex subglobose
      elements was isolated for the first time in Egypt from agricultural field soil
      cultivated with alfalfa (Trifolium alexandrinum) in El-Minia, Egypt. This fungus
      was found to be an active bio-control agent against P. ultimum var. ultimum, the
      damping-off organism of wheat. In agar plates, P. oligandrum parasitized P.
      ultimum var. ultimum hyphae with the aid of thin haustorial branches or infection
      pegs, eventually leading to host destruction. Incorporation of P. oligandrum into
      carboxymethylcellulose seed coating successfully eliminated pre-emergence damping
      off of wheat caused by P. ultimum var. ultimum, whereas Post-emergence damping
      off was prevented by adding inocula of P. oligandrum to the soil.

PMID- 16284715
TI  - Paclitaxel plus carboplatin-induced peripheral neuropathy. A prospective clinical
      and electrophysiological study in patients suffering from solid malignancies.
AB  - OBJECTIVE: The current study intended to determine the incidence, severity and
      reversibility of paclitaxel plus carboplatin (CP)-induced peripheral neuropathy
      (CPPN) and to describe its clinical and electrophysiological features. PATIENTS
      AND METHODS: We prospectively studied 21 adult patients scheduled to be treated
      with 6 courses of cumulative carboplatin plus paclitaxel (CP) regimens for a non
      myeloid malignancy. They were followed-up by neurological examination and
      electrophysiological study during chemotherapy and 3 months after its
      discontinuation. The severity of neurotoxicity was assessed by means of a
      modified peripheral neuropathy (PNP) score. RESULTS: Evidence of CPPN was
      recorded in 14 of the 21 patients (66.6 %). The sensory symptoms were present in
      the lower limbs first and then involved the upper limbs. No statistical
      significance, concerning the changes from baseline to subsequent mean scores in
      all motor conduction parameters examined,was revealed. By contrast, comparisons
      of the mean changes at baseline and each of the follow-up studies showed
      significant decrease in all sensory action potentials examined. The mean PNP
      scores for patients that manifested some grade of neurotoxicity were 17.9 +/-
      9.8. The followup data 3 months after the discontinuation of chemotherapy showed
      that the CP-induced neuropathy was at least partially reversed. CONCLUSIONS: CP
      induced neuropathy was symmetrical, distal and predominantly sensory in
      character, though minor to moderate motor signs were only evident in severely
      affected patients. Reversibility of CP-induced neuropathy was partially observed
      after the suspension of chemotherapy.

PMID- 16284720
TI  - A comparative study of Diaporthe/Phomopsis fungi on soybean from two different
      regions of the world.
AB  - A comparative study was conducted with soybean material presenting symptoms of
      the Diaporthe/Phomopsis complex that was collected in two distant geographical
      regions of the world: Beltsville, MA, USA, and Vojvodina, Yugoslavia. Contrasting
      with earlier findings, great variability in the disease symptoms was observed,
      and one or more Phomopsis species could be isolated from lesions presenting
      similar characteristics. Among the thirty-three isolates obtained from the
      lesions the following species were identified: D. phaseolorum var. caulivora, P.
      phaseoli (teleomorph D. phaseolorum var. sojae, rare), P. longicolla (found for
      the first time on the soybean fields of Yugoslavia), Phomopsis sp., and one
      culture showing intermediate characters of D. phaseolorum var. caulivora and D.
      phaseolorum var. sojae. Much diversity was also found in the cultural characters
      of the the isolates from both localities, presumably indicating evolutionary and
      adaptation processes.

PMID- 16284721
TI  - In vitro studies on the potential for biological control of Aspergillus flavus
      and Fusarium moniliforme by Trichoderma species. A study of the production of
      extracellular metabolites by Trichoderma species.
AB  - Culture filtrates of Trichoderma viride and Trichoderma harzianum were inhibitory
      of Fusarium moniliforme and, to a lesser extent, Aspergillus flavus. The degree
      of inhibition was, however, dependent on the carbon or nitrogen source
      incorporated into the medium. Scanning electron microscopy revealed the
      development of abnormal fruiting structures on exposure to some Trichoderma
      culture filtrate, while macroscopically, growth restriction and, in the case of
      A. flavus, altered colony colouration were observed. Based on the results of
      inverted colony culture, it would appear that some isolates of Trichoderma
      produce inhibitory volatile compounds. The production of possible antibiotics was
      also demonstrated. The aggressive behaviour (towards A. flavus and F.
      moniliforme) demonstrated by Trichoderma spp. may be partly explained by the
      liberation of extracellular enzymes by these fungi. An isolate of T. viride
      exhibited amylolytic, pectinolytic, proteolytic and cellulolytic activity. Based
      on the results of the present investigation, Trichoderma spp. are potential
      candidates for biocontrol of some mycotoxin-producing fungi, but there exists
      some doubt as to their osmotolerance within the air-dry seed.

PMID- 16284722
TI  - Synthesis, structure and anti-acetylcholinesterase activity of 4beta
      methoxymethyl-4beta-demethyl territrem B.
AB  - 4beta-Methoxymethyl-4beta-demethyl territrem B [5] was synthesized from 4beta
      hydroxymethyl-beta-demethyl territrem B [4] by treatment with dimethyl sulfate in
      methanolic NaOH. The structure of 5 was elucidated by uv, nmr and mass spectra.
      The IC50 of 5 on acetylcholinesterase (AChE) was 6.30 x 10(-5) M, which indicated
      0.4% of the anti-AChE activity of territrem B [2].

PMID- 16284723
TI  - Complete reversal of coenzyme specificity of isocitrate dehydrogenase from
      Haloferax volcanii.
AB  - Haloferax volcanii Ds-threo-isocitrate dehydrogenase (ICDH) was highly expressed
      in bacteria as inclusion bodies. The recombinant enzyme was refolded, purified
      and characterized, and was found to be NADP-dependent like the wild-type protein.
      Sequence alignment of several isocitrate dehydrogenases from evolutionarily
      divergent organisms including H. volcanii revealed that the amino acid residues
      involved in coenzyme specificity are highly conserved. Our objective was to
      switch the coenzyme specificity of halophilic ICDH by altering these conserved
      amino acids. We were able to switch coenzyme specificity from NADP+ to NAD+ by
      changing five amino acids by site-directed mutagenesis (Arg291, Lys343, Tyr344,
      Val350 and Tyr390). The five mutants of ICDH were overexpressed in Escherichia
      coli as inclusion bodies and each recombinant ICDH protein was refolded and
      purified, and its kinetic parameters were determined. Coenzyme specificity did
      not switch until all five amino acids were substituted.

PMID- 16284724
TI  - Inactivation kinetics of guanidinium chloride on Penaeus vannamei beta-N-acetyl-D
      glucosaminidase and the relationship of enzyme activity and its conformation.
AB  - The effects of guanidinium chloride (GuHCl) on the activity of Penaeus vannamei
      beta-N-acetyl-D-glucosaminidase (NAGase) have been studied. The results show that
      GuHCl, at appropriate concentrations, can lead to reversible inactivation of the
      enzyme, and the IC50 is estimated to be 0.6 M. Changes of activity and
      conformation of the enzyme in different concentrations of GuHCl have been studied
      by measuring the fluorescence spectra and its relative activity after
      denaturation. The fluorescence intensity of the enzyme decreases distinctly with
      increasing GuHCl concentrations, and the emission peaks appear red-shifted (from
      339.4 to 360 nm). Changes in the conformation and catalytic activity of the
      enzyme are compared. The extent of inactivation is greater than that of
      conformational changes, indicating that the active site of the enzyme is more
      flexible than the whole enzyme molecule. The kinetics of inactivation has been
      studied using the kinetic method of the substrate reaction. The rate constants of
      inactivation have been determined. The value of k(+0) is larger than that of
      k'(+0) which suggests that the enzyme is protected by substrate to a certain
      extent during guanidine denaturation.

PMID- 16284725
TI  - Monoclonal antibodies against soybean Bowman-Birk inhibitor recognize the
      protease-reactive loops.
AB  - Monoclonal antibodies against soybean Bowman-Birk protease inhibitor (BBI) have
      been generated and used to detect and quantify BBI in foods, soybean germplasm,
      and animal tissues and fluids. The purpose of this study was to determine the
      recognition sites of two monoclonal antibodies to BBI (mAb 238 and mAb 217) in
      relation to the protease-inhibitory sites of BBI. The results showed that (1) the
      binding of mAb 238 can be blocked by trypsin and that of mAb 217 by chymotrypsin;
      (2) the trypsin or chymotrypsin inhibitory activities of BBI are blocked by mAb
      238 or mAb 217, respectively; and (3) mAb 238 failed to recognize a tryptic loop
      mutant BBI variant and mAb 217 was unable to bind a chymotryptic loop mutant BBI
      variant. These findings demonstrate that the epitopes recognized by mAb 238 and
      mAb 217 reside, at least in part, in the tryptic and chymotryptic loops of BBI,
      respectively.

PMID- 16284726
TI  - Comparison of guanidine hydrochloride (GdnHCl) and urea denaturation on
      inactivation and unfolding of human placental cystatin (HPC).
AB  - The activity and conformational change of human placental cystatin (HPC), a low
      molecular weight thiol proteinase inhibitor (12,500) has been investigated in
      presence of guanidine hydrochloride (GdnHCl) and urea. The denaturation of HPC
      was followed by activity measurements, fluorescence spectroscopy and Circular
      Dichroism (CD) studies. Increasing the denaturant concentration significantly
      enhanced the inactivation and unfolding of HPC. The enzyme was 50% inactivated at
      1.5 M GdnHCl or 3 M urea. Up to 1.5 M GdnHCl concentration there was quenching of
      fluorescence intensity compared to native form however at 2 M concentration
      intensity increased and emission maxima had 5 nm red shift with complete
      unfolding in 4-6 M range. The mid point of transition was in the region of 1.5-2
      M. In case of urea denaturation, the fluorescence intensity increased gradually
      with increase in the concentration of denaturant. The protein unfolded completely
      in 6-8 M concentration of urea with a mid-point of transition at 3 M. CD
      spectroscopy shows that the ellipticity of HPC has increased compared to that of
      native up to 1.5 M GdnHCl and then there is gradual decrease in ellipticity from
      2 to 5 M concentration. At 6 M GdnHCl the protein had random coil conformation.
      For urea the ellipticity decreases with increase in concentration showing a
      sigmoidal shaped transition curve with little change up to 1 M urea. The protein
      greatly loses its structure at 6 M urea and at 8 M it is a random coil. The urea
      induced denaturation follows two-state rule in which Native-->Denatured state
      transition occurs in a single step whereas in case of GdnHCl, intermediates or
      non-native states are observed at lower concentrations of denaturant. These
      intermediate states are possibly due to stabilizing properties of guanidine
      cation (Gdn+) at lower concentrations, whereas at higher concentrations it acts
      as a classical denaturant.

PMID- 16284727
TI  - Purification and kinetic properties of 6-phosphogluconate dehydrogenase from rat
      small intestine.
AB  - 6-Phosphogluconate dehydrogenase (6PG) was purified from rat small intestine with
      36% yield and a specific activity of 15 U/mg. On SDS/PAGE, one band with a mass
      of 52 kDa was found. On native PAGE three protein and two activity bands were
      observed. The pH optimum was 7.35. Using Arrhenius plots, Ea, DeltaH, Q10 and Tm
      for 6PGD were found to be 7.52 kcal/mol, 6.90 kcal/mol, 1.49 and 49.4 degrees C,
      respectively. The enzyme obeyed "Rapid Equilibrium Random Bi Bi" kinetic model
      with Km values of 595 +/- 213 microM for 6PG and 53.03+/-1.99 microM for NADP.
      1/Vm versus 1/6PG and 1/NADP plots gave a Vm value of 8.91+/-1.92 U/mg protein.
      NADPH is the competitive inhibitor with a Ki of 31.91+/-1.31 microM. The
      relatively small Ki for the 6PGD:NADPH complex indicates the importance of NADPH
      in the regulation of the pentose phosphate pathway through G6PD and 6PGD.

PMID- 16284728
TI  - Artificial chaperone-assisted refolding of GuHCl-denatured alpha-amylase at low
      temperature: refolding versus aggregation.
AB  - Refolding of GuHCl-denatured alpha-amylase was investigated using the artificial
      chaperone-assisted method. Three different cationic detergents (CTAB, TTAB and
      DTAB) and two nonionic detergents (Tween 80 and Triton X-100) were evaluated as
      the capturing reagents along with alpha- and beta-CD as the stripping agents. The
      refolding yields, at a final protein concentration of 0.15 mg/ml, were 82, 71 and
      66% in the presence of beta-CD and CTAB, TTAB or DTAB, respectively. To improve
      the refolding yield and to suppress the extent of aggregation, the initial rate
      of the stripping step was slowed down by maintaining the refolding environment at
      4 degrees C for about 3 min followed by raising the temperature to 25 degrees C.
      Under this thermal procedure, the refolding yield and the extent of aggregation
      were changed from 82 and 25% at 25 degrees C to 94 and 7% at 4 degrees C,
      respectively. These findings may assist the activity recovery of recombinant
      proteins at relatively high concentrations.

PMID- 16284729
TI  - Disulfide linkages and a three-dimensional structure model of the extracellular
      ligand-binding domain of guanylyl cyclase C.
AB  - Guanylyl cyclase C (GC-C) is a single-transmembrane receptor that is specifically
      activated by endogenous ligands, including guanylin, and the exogenous ligand,
      heat-stable enterotoxin. Using combined HPLC separation and MS analysis
      techniques the positions of the disulfide linkages in the extracellular ligand
      binding domain (ECD) of GC-C were determined to be between Cys7-Cys94, Cys72
      Cys77, Cys101-Cys128 and Cys179-Cys226. Furthermore, a three-dimensional
      structural model of the ECD was constructed by homology modeling, using the
      structure of the ECD of GC-A as a template (van den Akker et al., 2000, Nature,
      406: 101-104) and the information of the disulfide linkages. Although the GC-C
      model was similar to the known structure of GC-A, importantly its ligand-binding
      site appears to be located on the quite different region from that in GC-A.

PMID- 16284730
TI  - Hereditary periodic fever and reactive amyloidosis.
AB  - Hereditary periodic fever syndromes (HPF) are a group of diseases characterised
      by recurrences of fever and inflammation separated by symptom-free intervals.
      Familial Mediterranean fever (FMF) is the most frequent entity within this group
      of disorders which further consists of hyperimmunoglobulinaemia D and periodic
      fever syndrome (HIDS), tumour necrosis factor receptor-associated periodic
      syndrome (TRAPS) and cryopyrin-associated periodic syndrome (CAPS). In recent
      years the causative genes have been identified. Reactive amyloidosis is a severe
      complication of HPFs. This is caused by deposition of fibrils that consist of the
      proteolytically cleaved acutephase protein serum amyloid A (SAA). Several factors
      have been identified that modulate the risk for developing amyloidosis, including
      SAA concentrations, polymorphisms in the SAA gene and ethnic origin. Furthermore,
      the risk of developing amyloidosis varies widely between the different HPFs.
      Colchicine is the cornerstone in the management of FMF, as it reduces the
      severity and frequency of attacks and is also effective in preventing
      amyloidosis. In the other HPFs, the introduction of anticytokine-based therapies
      is a promising new option in treating these inflammatory conditions and they
      potentially can prevent amyloidosis.

PMID- 16284731
TI  - Effect of different levels of cigarette smoking on lipid peroxidation,
      glutathione enzymes and paraoxonase 1 activity in healthy people.
AB  - The purpose of this study was to examine the effect of different levels of
      cigarette smoking on lipid peroxidation, glutathione enzymes and paraoxonase 1
      (PON1) activity in a healthy population. The study included 130 subjects who were
      classified as mild (<or=10 cigarettes daily, Group I, n=30), moderate (11-20
      cigarettes daily, Group II, n=35), heavy (>20 cigarettes daily, Group III, n=33)
      and never smokers (controls, Group IV, n=32). Malondialdehyde (MDA) levels, PON1
      and erythrocyte glutathione enzyme activities were measured. MDA levels were
      significantly higher in smokers than never smokers (P<0.05 for Group I, P<0.001
      for Group II and III). PON1 activity was significantly lower in heavy smokers
      (P<0.001). Glutathione peroxidase (GSH-Px) activity was significantly lower in
      the smokers (P<0.0001). Glutathione reductase (GR) activity was significantly
      higher in smokers (P<0.0001). MDA levels negatively correlated with PON1 and GSH
      PX activities (P<0.01), whereas they positively correlated with GR activities
      (P<0.001). At every level, cigarette smoking is associated with increased lipid
      peroxidation and causes an impairment in antioxidant systems.

PMID- 16284732
TI  - Distribution of somatostatin in pancreatic ductal adenocarcinoma remodels the
      normal pattern of the protein during foetal pancreatic development: an
      immunohistochemical analysis.
AB  - AIM: To determine the immunoreactivity of somatostatin during the development of
      the human fetal pancreas and pancreatic ductal adenocarcinoma, given that,
      somatostatin-positive cells were demonstrated either into its embryonic anlage or
      into pancreatic cancer. METHODS: Tissue sections from 15 pancreatic fetal
      specimens, and an equal number of ductal adenocarcinoma specimens were assessed.
      RESULTS: The density of positive cells in the primitive exocrine ductal
      epithelium and endocrine epithelium was significantly different from the relevant
      density in the neoplastic pancreatic tissue of mixed (ductal-endocrine) and pure
      ductal type (P1=0.021 P2=0.001, P3<0.0001, P4=0.003 respectively). The above
      values were estimated from the 8th to 10th week. There was no significant
      difference in the density of positive cells in the mantle zone of the islets from
      the 13th to the 24th week, and the neoplastic tissue of mixed (P5=0.16) and pure
      ductal type (P6=0.65). CONCLUSION: The immunostaining for somatostatin identifies
      a subgroup of pancreatic ductal adenocarcinomas with a neuroendocrine component,
      (initially considered as pure ductal tumors), and mixed ductal and neuroendocrine
      tumors. This pattern of expression in neoplasms recapitulates the normal pattern
      during the embryonal development of the organ, raising the question of
      therapeutic efficacy of somatostatin and analogues as monotherapy in pancreatic
      cancer management.

PMID- 16284733
TI  - Interleukin-6 polymorphism and Helicobacter pylori infection in Brazilian adult
      patients with chronic gastritis.
AB  - Helicobacter pylori is recognised as the most common cause of chronic active
      gastritis and this bacterium is also an important pathogenic factor in peptic
      ulcer disease. The biological factors that influence clinical outcome in H.
      pylori infection have been extensively studied. In addition to immunological
      factors in the host, bacterial virulence determinants in H. pylori strains are
      likely to play a crucial role in gastric cancer development. Singlenucleotide
      polymorphisms at the 5' flanking region of the interleukin (IL)-6 gene promoter
      (G or C at -174 base) have been identified and individuals with the G allele at
      position -174 have been shown to produce higher levels of IL-6 than those with
      the C/C genotype. The mucosal levels of IL-6 were reported to be increased in H.
      pylori-associated gastritis. The present study was conducted to examine any
      relationship between inflammatory cytokine polymorphisms and the inflammatory
      process in mucosa infected by H. pylori. In our study we did not find any
      association between the C and G alleles in adult patients with chronic gastritis
      and inflammatory process in gastric mucosa.

PMID- 16284734
TI  - Lipid peroxidation levels in patients with acute brucellosis.
AB  - The purpose of this study was to investigate levels of lipid peroxidation,
      indicated by plasma malondialdehyde (MDA), with consideration of clinical status
      and treatment outcomes in patients with acute brucellosis. Plasma MDA levels were
      measured in patients with acute brucellosis and healthy subjects. Significantly
      higher MDA levels were detected in plasma of patients with acute brucellosis
      compared to controls (P<0.01). Plasma levels of MDA were significantly decreased
      after the brucellosis treatment (P<0.01). The results of the present study
      indicate for the first time that a considerable level of lipid peroxidation is
      involved in acute brucellosis cases and this may be of importance with respect to
      the understanding of disease pathogenesis and may serve as a target for treatment
      regime.

PMID- 16284735
TI  - The Coxsackie-adenovirus receptor has elevated expression in human breast cancer.
AB  - The Coxsackie-adenovirus receptor (CAR) is the primary site for adenovirus
      attachment during infection and has been used as a delivery mechanism for gene
      therapies. However, the expression profile of the receptor in cancer,
      particularly in clinical breast cancer, is poorly reported. This study evaluated
      the expression of CAR in human breast cancers. Frozen sections from breast cancer
      primary tumours (matched tumour n=114 and background n=30) were immunostained
      with CAR antibody. RNA was reverse transcribed and analysed by quantitative-PCR
      (Q-PCR). Levels of CAR were analysed against the clinical background, with a
      median follow-up of 72 months. Staining intensity of CAR was increased within
      tumour sections compared to background tissue. Q-PCR revealed significantly
      elevated levels of CAR transcript in breast tumours (32 313+/-7067 mean+/-SE vs.
      background tissue 11 483+/-7069, P=0.023). CAR expression also increased with
      grade of tumour. Patients who had tumour metastases also showed elevated levels
      of CAR expression (metastasis: 61 940+/-22 749 vs. alive and well 29 655+/-8149),
      however those with local recurrences had reduced levels of CAR. Ductal carcinomas
      expressed lower levels of CAR compared to tumours of other types. Tumours with
      nodal involvement were also associated with higher levels of CAR (node positive
      2320 median vs. node negative 1077.5). Levels of CAR were significantly
      correlated with long-term survival over a period of 6 years (P=0.004, univariate
      analysis). We conclude that CAR expression is elevated in primary breast cancers.
      This may have a bearing on its use as means of delivery for gene therapy and
      suggests that further work is necessary to understand this complex molecule.

PMID- 16284736
TI  - Molecular study of the tumour suppressor gene PTEN in gastric adenocarcinoma in
      Brazil.
AB  - Among all tumours diagnosed worldwide, gastric adenocarcinoma is the second most
      frequent type of malignancy. In Brazil, it is estimated to be the fifth most
      frequent type of neoplasia. According to the classification of Lauren, these
      tumours are divided into well differentiated and ill differentiated gastric
      adenocarcinomas. There are studies suggesting that the first type develops
      through remodulation of genes involved in the suppressor pathway and the second
      through remodulation of genes belonging to the mutational pathway. The gene PTEN
      is located in region 10q23 and is altered in several human tumours. In gastric
      cancer, this gene is thought to take part in the suppressor pathway. In our
      study, DNA was obtained from 48 gastric adenocarcinoma samples, amplified,
      screened for all exons of the PTEN gene by PCR-SSCP and then confirmed by
      sequencing. There was only one sample that presented an alteration and that was a
      transversion. Our results corroborate the hypothesis that somatic alterations in
      the PTEN gene are rare events in gastric cancer.

PMID- 16284738
TI  - [Renal cancer study activities in Germany. Drug therapy].
AB  - Drug therapy of advanced renal cell carcinoma underwent rapid changes.
      Monotherapeutic, placebo-controlled protocols -- and more recently combinations
      of different targeted drugs -- dominated the global clinical studies in the past
      2 years. The preliminary results are almost encouraging and international
      investigators, supported by the pharmaceutical industry, were most successful in
      enrolling patients quickly. The present article reviews the recent German drug
      study activities and indicates potential future projects.

PMID- 16284737
TI  - [Microcirculatory monitoring of sepsis].
AB  - Microcirculatory dysfunctions play a central role in the pathophysiology of
      sepsis and shock. Modern methods enable microvascular monitoring in man and offer
      the possibility to test the effect of novel therapeutical strategies for sepsis.
      Furthermore, these techniques may be future tools for the monitoring of
      critically ill patients. In this review, we will describe four microvascular
      monitoring devices and give an overview of the microcirculatory changes observed
      during the course of sepsis. Laser Doppler fluxmetry is an easy to use
      noninvasive technique to measure tissue perfusion enabling monitoring of the
      effect of different catecholamines on the gastric perfusion during sepsis.
      Increased microvascular permeability and altered blood flow in septic patients
      can be quantified by venous congestion plethysmography. Alterations in sublingual
      microvascular blood flow are detected by intravital microscopy in septic patients
      and were identified as an outcome predictor. Furthermore, the role of
      gastrointestinal pCO2-tonometry for microcirculatory monitoring of the perfusion
      of splanchnic organs during sepsis is discussed. The true clinical value of these
      techniques has yet to be established and will depend on larger clinical trials
      showing an impact on diagnostics and patient management.

PMID- 16284739
TI  - Alveolar plasminogen activator inhibitor-1 predicts ARDS in aspiration
      pneumonitis.
AB  - OBJECTIVE: To test the hypothesis that alveolar plasminogen activator inhibitor-1
      (PAI-1) can identify patients with witnessed aspiration at risk for progression
      to acute respiratory distress syndrome (ARDS). DESIGN: Prospective observational
      study. SETTING: Medical intensive care unit in a tertiary care center. PATIENTS:
      Fifty-one patients with witnessed aspiration who had a PaO2/FIO2<300 for a period
      no less than 4 h from admission. INTERVENTIONS: Alveolar fluid sampling was
      performed within 8 h of intubation via luminal suction of the distal airways
      using a 13-Fr catheter. Plasma levels were collected simultaneously by
      venipuncture. MEASUREMENTS AND RESULTS: Alveolar PAI-1 antigen levels were more
      than five times higher in those who progressed to ARDS than in those with
      uncomplicated aspiration pneumonitis (2687+/-1498 ng/ml vs. 587+/-535 ng/ml,
      respectively; p<0.001), while plasma levels of PAI-1 antigen were not
      significantly different between the two groups. The measured activity of PAI-1
      antigen paralleled the levels observed in both media. A cut-off level of alveolar
      PAI-1 >1518 ng/ml was found to be 82.4% (56.6%-96.0%) sensitive and 97.1% (84.6%
      99.5%) specific in predicting progression to ARDS. There was also a significant
      inverse relationship between elevation of PAI-1 antigen levels and the degree of
      lung injury as assessed by the days of unassisted ventilation (r2=0.37; p<0.001).
      CONCLUSIONS: Elevation of alveolar PAI-1 antigen levels postaspiration is the
      consequence of local rather than systemic activation of the fibrinolytic system.
      Measurement of alveolar PAI-1 antigen levels can be a useful clinical marker in
      predicting progression to ARDS after gastric aspiration.

PMID- 16284740
TI  - Primary stability of four different implants for opening wedge high tibial
      osteotomy.
AB  - Since a significant number of implant failures have been reported in association
      with the procedure of open wedge valgus high tibial osteotomy, the initial
      biomechanical stability of different fixation devices was investigated in this
      study. Fifteen third generation Sawbones composite tibiae were used as a model.
      Four different plates were tested: a short spacer plate (OWO) (n = 4), a short
      spacer plate with multi-directional locking bolts (MSO) (n = 5), a prototype
      version of a long spacer plate with multi-directional locking bolts (MSOnew) (n =
      2), and a long medial tibia plate fixator with locking bolts (MPF) (n = 4). All
      opening wedge osteotomies were performed by the same surgeon (PL) in a
      standardized fashion. Axial compression of the tibiae was performed using a
      materials testing machine under standardized alignment of the loading axis.
      Single load to failure tests as well as load-controlled cyclical failure tests
      were performed. The required force and cycles to failure were recorded. Osteotomy
      gap motion was measured using linear displacement transducers. Residual stability
      after failure of the opposite lateral cortex was analysed. Failure occurred at
      the lateral cortex bone-bride in all tested implants. The rigid long plate
      fixator (MPF) resisted the greatest amount of force (2,881 N) in the single load
      to failure tests. In the cyclical load-to-failure tests, the constructs with MPF
      resisted more than twice the amount of loading cycles when compared to the short
      spacer plates. The osteotomy gap motion was smallest in the MPF, with a reduction
      of the displacements of up to 65, 66 and 88%, when compared to OWO, MSO and
      MSOnew, respectively. The highest residual stability after failure of the lateral
      cortex was observed in MPF as well. The results suggest that the implant design
      strongly influences the primary stability of medial opening wedge tibial
      osteotomy. A rigid long plate fixator with angle-stable locking bolts yields the
      best results.

PMID- 16284741
TI  - Cellular location of insulin-triggered signals and implications for glucose
      uptake.
AB  - Insulin stimulation of glucose uptake into muscle and fat cells requires movement
      of GLUT4-containing vesicles from intracellular compartments to the plasma
      membrane. Accordingly, insulin-derived signals must arrive at and be recognized
      by the appropriate intracellular GLUT4 pools. We describe the insulin signals
      participating in GLUT4 translocation, and review evidence that they are recruited
      to intracellular membranes in conjunction with cytoskeletal elements. Such
      segregation may facilitate the encounter between signals and target vesicles. In
      most animal and cellular models of insulin resistance, insulin-stimulated GLUT4
      translocation to the plasma membrane is reduced. Insulin resistance caused by
      oxidative stress does not affect early insulin signals, rather their
      intracellular localization is altered. In this and several other insulin
      resistant states, insulin-induced actin remodelling is concomitantly diminished.
      We summarize evidence suggesting that spatial localization of signals is critical
      for efficient insulin action, and that the cytoskeleton may act as a scaffold to
      promote efficient translocation of GLUT4 to the cell surface.

PMID- 16284743
TI  - Transient expression and insertional mutagenesis of Puccinia triticina using
      biolistics.
AB  - The fungal genus Puccinia contains more than 4,000 species. Puccinia triticina,
      causal agent of wheat leaf rust, is an economically significant, biotrophic
      basidiomycete. Little is known about the molecular biology of this group, and
      tools for understanding gene function have not yet been established. A set of
      parameters was established for the transient transformation of urediniospores.
      The expression of three heterologous promoters (actin, elongation factor 1-alpha,
      and Hss1, Heat Shock 70 protein), derived from Puccinia graminis, was evaluated
      along with the potential for insertional mutagenesis. The UidA (GUS) gene was
      used as a marker for transient expression. When transferred into P. triticina
      urediniospores, transient expression was observed across four helium pressures
      using one size of gold and three sizes of tungsten microprojectiles. Each of the
      three promoters displayed strong transient expression in germinated
      urediniospores; however, higher numbers of GUS-positive urediniospores were
      observed when either the actin or Hss1 promoters were used. Possible concomitant
      insertional mutagenesis of several avirulence genes was selected in wheat
      cultivars harboring the cognate resistance genes. Using a linearized cloning
      plasmid, stable integration into the genome was achieved as demonstrated by PCR
      and sequencing analysis.

PMID- 16284742
TI  - Integrin stimulation induces calcium signalling in rat cardiomyocytes by a NO
      dependent mechanism.
AB  - The myocardial stretch-induced increase in intracellular [Ca(2+)] ([Ca(2+)](i))
      is considered to be caused by integrin stimulation. Myocardial stretch is also
      associated with increased nitric oxide (NO) formation. We hypothesised that NO is
      implicated in calcium signalling following integrin stimulation. Integrins of
      neonatal rat cardiomyocytes were stimulated with a pentapeptide containing the
      Arg-Gly-Asp (RGD) sequence. [Ca(2+)](i) was measured with Fura2, [NO](i) was
      measured with DAF2 and phosphorylation of focal adhesion kinase (FAK) was
      monitored with immunofluorescence techniques. Integrin stimulation increased both
      [NO](i) and [Ca(2+)](i), the latter response being inhibited by ryanodine
      receptor-2 (RyR2) blockers and by N(G)-monomethyl-L-arginine (L-NMMA), an
      inhibitor of NOS, but resistant to GdCl(3), diltiazem and wortmannin. Integrin
      induced intracellular Ca(2+) release thus appears to be independent of the influx
      of extracellular Ca(2+) and phosphatidylinositol-3 kinase activity. In addition,
      integrin stimulation induced phosphorylation of FAK. Our results provide evidence
      for an integrin-induced Ca(2+) release from RyR2 which is mediated by NO
      formation, probably via FAK-induced NOS activation.

PMID- 16284744
TI  - Bacterial growth and substrate degradation by BTX-oxidizing culture in response
      to salt stress.
AB  - Interactions between microbial growth and substrate degradation are important in
      determining the performance of trickle-bed bioreactors (TBB), especially when
      salt is added to reduce biomass formation in order to alleviate media clogging.
      This study was aimed at quantifying salinity effects on bacterial growth and
      substrate degradation, and at acquiring kinetic information in order to improve
      the design and operation of TBB. Experiment works began by cultivating a mixed
      culture in a chemostat reactor receiving artificial influent containing a mixture
      of benzene, toluene, and xylene (BTX), followed by using the enrichment culture
      to degrade the individual BTX substrates under a particular salinity, which
      ranged 0-50 g l(-1) in batch mode. Then, the measured concentrations of biomass
      and residual substrate versus time were analyzed with the microbial kinetics;
      moreover, the obtained microbial kinetic constants under various salinities were
      modeled using noncompetitive inhibition kinetics. For the three substrates the
      observed bacterial yields appeared to be decreased from 0.51-0.74 to 0.20-0.22 mg
      mg(-1) and the maximum specific rate of substrate utilization, q, declined from
      0.25-0.42 to 0.07-0.11 h(-1), as the salinity increased from 0 to 50 NaCl g l(
      1). The NaCl acted as noncompetitive inhibitor, where the modeling inhibitions of
      the coefficients, K ( T(S)), were 22.7-29.7 g l(-1) for substrate degradation and
      K ( T(mu)), 13.0-19.0 g l(-1), for biomass formation. The calculated ratios for
      the bacterial maintenance rate, m (S), to q, further indicated that the
      percentage energy spent on maintenance increased from 19-24 to 86-91% as salinity
      level increased from 0 to 50 g l(-1). These results revealed that the bacterial
      growth was more inhibited than substrate degradation by the BTX oxidizers under
      the tested salinity levels. The findings from this study demonstrate the
      potential of applying NaCl salt to control excessive biomass formation in
      biotrickling filters.

PMID- 16284745
TI  - Decisions, decisions, decisions.

PMID- 16284746
TI  - Studies of the association of the GNB3 825C>T polymorphism with components of the
      metabolic syndrome in white Danes.
AB  - AIMS/HYPOTHESIS: The 825C>T polymorphism in the gene encoding the G protein beta3
      subunit (GNB3) causes enhanced G protein activation and increased in vitro cell
      proliferation. This polymorphism is also repeatedly associated with an increased
      risk of hypertension and has been studied in relation to obesity with divergent
      results. Only a few association studies have investigated whether this
      polymorphism is related to type 2 diabetes or the metabolic syndrome. We
      estimated the impact of the GNB3 825C>T polymorphism in relatively large-scale
      association studies of common phenotypes of the metabolic syndrome. MATERIALS AND
      METHODS: The GNB3 825C>T polymorphism was genotyped in 7,518 white Danish
      subjects using mass spectrometry analysis of PCR products. Case-control studies
      were undertaken for obesity, hypertension, type 2 diabetes and the metabolic
      syndrome, and a meta-analysis including data from the present study and previous
      studies of hypertension was performed. Quantitative trait studies of metabolic
      variables were carried out in 4,387 glucose-tolerant subjects. RESULTS: We
      observed minor differences in 825C>T genotype distributions for type 2 diabetes
      (CC/CT/TT 49/41/10% (control) vs 46/46/9% (cases), respectively, p=0.007);
      however, after correction for multiple testing, these were not statistically
      significant. No association was found with hypertension, obesity or the metabolic
      syndrome. Curiously, the T allele was associated with nominally lower systolic
      and diastolic blood pressure levels-a finding in contrast with most previous
      studies-but not with other metabolic variables. Meta-analysis demonstrated a high
      degree of heterogeneity between study populations of different ethnic origin.
      Although there was a tendency towards an increased risk of hypertension among
      825T allele carriers, this was not statistically significant.
      CONCLUSIONS/INTERPRETATION: The present study suggests no major involvement of
      the GNB3 825C>T polymorphism in components of the metabolic syndrome.

PMID- 16284747
TI  - Rapid emergence of effect of atorvastatin on cardiovascular outcomes in the
      Collaborative Atorvastatin Diabetes Study (CARDS).
AB  - AIMS/HYPOTHESIS: The aim of this study was to determine the pattern of the effect
      of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin on
      cardiovascular events in patients with type 2 diabetes and no prior history of
      cardiovascular disease (CVD). MATERIALS AND METHODS: A post hoc analysis of data
      from the Collaborative Atorvastatin Diabetes Study (CARDS), a randomised, placebo
      controlled trial of 2,838 patients with type 2 diabetes, was performed. Patients
      received atorvastatin (10 mg daily) or placebo and were evaluated for
      cardiovascular and other outcomes over a median follow-up period of 3.9 years.
      Cox proportional hazards modelling was carried out, and the hazard ratios
      calculated for various times after randomisation to treatment were investigated.
      RESULTS: A reduction in the primary endpoint of major CVD events was apparent and
      statistically significant as soon as 18 months after treatment initiation. The
      effect of atorvastatin on CHD events was apparent by 6 months, and at 1 year was
      similar to the 37% relative risk reduction observed at trial closure.
      CONCLUSIONS/INTERPRETATION: Atorvastatin alters the pathogenesis of CVD rapidly,
      such that the effect on cardiovascular events is apparent within months of
      initiation of therapy.

PMID- 16284748
TI  - Gene expression profiling in skeletal muscle of Zucker diabetic fatty rats:
      implications for a role of stearoyl-CoA desaturase 1 in insulin resistance.
AB  - AIMS/HYPOTHESIS: Insulin resistance in skeletal muscle is a hallmark of type 2
      diabetes. Therefore, we sought to identify and validate genes involved in the
      development of insulin resistance in skeletal muscle. MATERIALS: Differentially
      regulated genes in skeletal muscle of male obese insulin-resistant, and lean
      insulin-sensitive Zucker diabetic fatty (ZDF) rats were determined using
      Affymetrix microarrays. Based on these data, various aspects of glucose disposal,
      insulin signalling and fatty acid composition were analysed in a muscle cell line
      overexpressing stearoyl-CoA desaturase 1 (SCD1). RESULTS: Gene expression
      profiling in insulin-resistant skeletal muscle revealed the most pronounced
      changes in gene expression for genes involved in lipid metabolism. Among these,
      Scd1 showed increased expression in insulin-resistant animals, correlating with
      increased amounts of palmitoleoyl-CoA. This was further investigated in a muscle
      cell line that overexpressed SCD1 and accumulated lipids, revealing impairments
      of glucose uptake and of different steps of the insulin signalling cascade. We
      also observed differential effects of high-glucose and fatty acid treatment on
      glucose uptake and long-chain fatty acyl-CoA profiles, and in particular an
      accumulation of palmitoleoyl-CoA in cells overexpressing SCD1.
      CONCLUSIONS/INTERPRETATION: Insulin-resistant skeletal muscle of ZDF rats is
      characterised by a specific gene expression profile with increased levels of
      Scd1. An insulin-resistant phenotype similar to that obtained by treatment with
      palmitate and high glucose can be induced in vitro by overexpression of SCD1 in
      muscle cells. This supports the hypothesis that elevated SCD1 expression is a
      possible cause of insulin resistance and type 2 diabetes.

PMID- 16284749
TI  - Isolation and characterization of a gene cluster for dibenzofuran degradation in
      a new dibenzofuran-utilizing bacterium, Paenibacillus sp. strain YK5.
AB  - Spore-forming bacterial strains capable of utilizing dibenzofuran (DF) as a sole
      source of carbon and energy were isolated. Characteristics of the isolates
      justified their classification into the genus Paenibacillus, and their closest
      relative was P. naphthalenovorans. Degenerate primers for aromatic hydrocarbon
      dioxygenase alpha subunit (AhDOa) genes and genomic DNA of the strain YK5 were
      used for gene isolation. The nucleotide sequences of clones of the PCR products
      revealed that the strain YK5 carries at least five different AhDOa genes.
      Northern hybridization analysis showed that one of the AhDOa genes was
      transcribed under DF-containing culture conditions. A gene cluster encoding the
      AhDOa was isolated. The genes predicted to encode extradiol dioxygenase (dbfB)
      and hydrolase (dbfC) were found to be an upstream of genes encoding the alpha and
      beta subunit of the AhDO (dbfA1 and dbfA2, respectively); the latter two gene
      products showed 60 and 53% identity to the amino acid sequences of DbfA1 and
      DbfA2 of Terrabacter sp. DBF63, respectively. Two Paenibacillus validus JCM 9077
      strains transformed with the dbf gene clusters acquired the ability to convert DF
      to 2,2',3-trihydroxybiphenyl (THBP) and salicylic acid (SAL). These results
      suggest that the enzymes encoded by the gene cluster isolated in this study are
      involved in DF metabolism in YK5.

PMID- 16284750
TI  - The influence of amphetamine on language activation: an fMRI study.
AB  - RATIONALE: Amphetamine administration has been found to affect the degree of
      cerebral dominance for motor control in animals. In humans, cerebral dopamine
      neurotransmission is also correlated to motor dominance. Since language dominance
      is related to motor dominance, amphetamine might also affect cerebral dominance
      for language. METHODS: To test this hypothesis, language activation was measured
      twice with functional magnetic resonance imaging in ten healthy right-handed men
      in a double-blind crossover design 2 h after amphetamine or placebo
      administration. RESULTS: Language-related activation increased significantly in
      task-related areas, but the individual lateralization index was not affected in
      the amphetamine condition as compared to placebo. CONCLUSIONS: This finding
      suggests that short-termed alterations in the dopaminergic neurotransmission do
      not affect language dominance.

PMID- 16284751
TI  - Blood oxygenation level dependent contrast resting state networks are relevant to
      functional activity in the neocortical sensorimotor system.
AB  - The relevance of correlations between blood oxygenation level dependent (BOLD)
      signal changes across the brain acquired at rest (resting state networks, or RSN)
      to functional networks was tested using two quantitative criteria: (1) the
      localisation of major RSN correlation clusters and the task-related maxima
      defined in BOLD fMRI signal changes from the same subjects; and (2) the relative
      hemispheric lateralisation (LI) of BOLD fMRI signal changes in sensorimotor
      cortex. RSN were defined on the basis of signal changes correlated with that of a
      "seed" voxel in the primary sensorimotor cortex. We found a generally close
      spatial correspondence between clusters of correlated BOLD signal change in RSN
      and activation maxima associated with hand movement. Conventional BOLD fMRI
      during active hand movement showed the expected wide variation in relative
      hemispheric lateralisation of LI for sensorimotor cortex across the subjects.
      There was a good correlation between LIs for the active hand movement task and
      the RSN (r=0.74, p<0.001). The RSN thus define anatomically relevant regions of
      motor cortex and change with functionally relevant variations in hemispheric
      lateralisation of sensorimotor cortical interactions with hand movement.

PMID- 16284752
TI  - Simple spike firing in the posterior lateral cerebellar cortex of Macaque Mulatta
      was correlated with success-failure during a visually guided reaching task.
AB  - Evidence has been accumulating which supports a role for the cerebellum in motor
      learning. Motor learning is though to be mediated by complex spikes acting as an
      error signal, which when firing in conjunction with simple spike activity modify
      synapses between parallel fibers and Purkinje cells. We studied the activity of
      neurons in the posterior lateral cerebellar cortex of macaques that were
      performing reaches to visual targets. We found that simple spike firing in many
      of these neurons was modulated by whether the monkey successfully hit the target
      or not. The success-failure modulation was present for reaches using either arm
      and could persist for several hundred milliseconds into a period when the monkey
      was constrained from moving its arms. This temporally extended success-failure
      activity could interact with complex spike firing in order to enhance learning,
      particularly when the motor command is temporally separated from sensory
      feedback.

PMID- 16284754
TI  - Practice effects on local and global dynamics of the ski-simulator task.
AB  - This experiment examined the acquisition of the global and local dynamics of the
      changes in the total body center of mass-platform and inter-limb coordination
      motions over the course of practice (20, 30 s trials each day for 7 days) in the
      ski-simulator task. Four blocks of trials, representative of early, moderate, and
      extensive practice were analyzed through power spectrum and coherence analyses.
      The oscillation frequencies of the knee joints became tuned to that of the
      platform-performer system and there were changes due to practice in the lower
      inter-limb coordination dynamics independent of the center of mass and platform
      coordination pattern. Acquisition of global level dynamics occurs to achieve a
      stable task solution that can allow for degenerate frequency- and phase-locking
      of the mechanical degrees of freedom at both the local intra- and inter-limb
      levels.

PMID- 16284753
TI  - Intercolumnar synchronization of neuronal activity in rat barrel cortex during
      patterned airjet stimulation: a laminar analysis.
AB  - We used cross-correlation analysis to characterize the incidence and strength of
      stimulus-induced neuronal synchronization in different layers of SI barrel cortex
      and as a function of neuronal location in different barrel columns. To reduce the
      possibility of evoking responses that were coordinated by simultaneous whisker
      movements, multiple whiskers were sequentially stimulated with airjets that moved
      back-and-forth across the peripheral whisker pad. From a sample of 627 neurons,
      we characterized 1,182 neuron pairs and found that 687 (58.1%) of these displayed
      significant peaks of synchronized activity that exceeded the 99.9% confidence
      limits. Whereas 88% of the infragranular neuron pairs were synchronized during
      whisker stimulation, only 30% of the neuron pairs in the granular or
      supragranular layers displayed synchronized responses. The strength of
      synchronization, as measured by the correlation coefficient, was significantly
      higher in the infragranular layers than in the other layers. These results
      indicate that synchronized outputs from the infragranular layers do not depend on
      synchronized inputs from the upper cortical layers. We also found that
      synchronization varies with the spatial configuration of the neurons and is
      strongest for neuron pairs residing in the same row. Given the dense local
      projections between neighboring barrel columns in the same row, our results
      indicate that neuronal synchronization is greatest when stimuli simultaneously
      activate those peripheral receptors whose cortical representations are most
      densely interconnected. Finally, we compared the present results with
      synchronized responses in somatosensory (SI) barrel cortex that were evoked by
      controlled, pulsatile whisker movements in a previous study. We conclude that
      highly-controlled whisker stimulation increases stimulus coordination and may
      exaggerate the incidence and strength of synchronization among neurons in the
      granular or supragranular layers.

PMID- 16284755
TI  - Short-latency afferent inhibition during selective finger movement.
AB  - During individual finger movement, two opposite phenomena occur at the level of
      the central nervous system that could affect other intrinsic hand muscle
      representations, unintentional co-activation, and surround inhibition (SI). At
      rest, excitability in the motor cortex (M1) is inhibited at about 20 ms after
      electric stimulation of a peripheral nerve [short-latency afferent inhibition
      (SAI)]. We sought to determine whether SAI changes during selective index finger
      movement. Effects were measured by the response to transcranial magnetic
      stimulation in two functionally distinct target muscles of the hand [abductor
      digiti minimi muscle (ADM), first dorsal interosseus muscle (FDI)]. An increase
      in SAI in the ADM during index finger movement compared to at rest could help
      explain the genesis of SI. Electrical stimulation was applied to either the
      little finger (homotopic for ADM, heterotopic for FDI) or the index finger
      (heterotopic for ADM, homotopic for FDI). During index finger movement, homotopic
      SAI was present only in the ADM, and the effect of peripheral stimulation was
      greater when there was less co-activation. Heterotopic SAI found at rest
      disappeared with movement. We conclude that during movement, homotopic SAI on the
      muscle in the surround of the intended movement may contribute to SI.

PMID- 16284757
TI  - The automatic extraction and use of information from cues and go signals in an
      anti-saccade task.
AB  - In a gap antisaccade task that exogenously cues the side that subjects should
      antisaccade to, subjects find it hard to look away from the suddenly appearing go
      signal. Surprisingly, subjects are unaware of the majority of the prosaccade
      errors they make, and these errors remain unrecognised even when corrected by a
      second saccade requiring twice the amplitude [Fischer B, Weber H (1992) in Exp
      Brain Res 89:415-424]. This paper presents an extended antisaccade task that
      investigates what information, if any, subjects extract from redundant cues and
      go signals. In Exp. 1, multiple saccade locations were introduced and the go
      signal specified the goal location. A redundant cue appeared, prior to the go
      signal, in the antisaccade goal location (valid) or in the alternative location
      on the same side (invalid). In Exp. 2, motivational value was assigned to the go
      signal. The use of multiple locations showed that subjects automatically extract
      irrelevant positional information from the cue, which affects the programming of
      subsequent correct and error saccades. When the cued location was also the goal
      location, antisaccade reaction times were significantly reduced. The results from
      Exp. 2 showed that subjects also extract information from the go signal. Errors
      made to a go signal associated with a higher monetary value were initiated
      significantly faster than those to a lower monetary value. This study has shown
      that the visual stimuli used in this antisaccade task do more than initiate
      orienting sets: Their properties can influence the programming of both accurate
      actions and errors.

PMID- 16284756
TI  - Comparison of population activity in the dorsal premotor cortex and putamen
      during the learning of arbitrary visuomotor mappings.
AB  - A previous study found that as monkeys learned novel mappings between visual cues
      and responses, neuronal activity patterns evolved at approximately the same time
      in both the dorsal premotor cortex (PMd) and the putamen. Here we report that, in
      both regions, the population activity for novel mappings came to resemble that
      for familiar ones as learning progressed. Both regions showed activity
      differences on trials with correct responses versus those with incorrect ones. In
      addition to these common features, we observed two noteworthy differences between
      PMd and putamen activity during learning. After a response choice had been made,
      but prior to feedback about the correctness of that choice (reward or nonreward),
      the putamen showed a sustained activity increase in activity, whereas PMd did
      not. Also in the putamen, this prereward activity was highly selective for the
      specific visuomotor mapping that had just been performed, and this selectivity
      was maintained until the time of the reward. After performance reached an
      asymptote, the degree of this selectivity decreased markedly to the level typical
      for familiar visuomotor mappings. These findings support the hypothesis that
      neurons in the striatum play a pivotal role in associative learning.

PMID- 16284759
TI  - Dysplasia epiphysealis hemimelica of the tibial tubercle.
AB  - Dysplasia epiphysealis hemimelica (DEH) is a rare skeletal dysplasia with
      epiphyseal involvement first described by Mouchet and Belot in 1926. Lower
      extremity involvement is common and might involve a single or multiple epiphyses
      in the affected extremity. We report an unusual case of involvement of the tibial
      tubercle in a girl aged 4 years 8 months, and we present the clinical,
      radiographic and pathologic findings. We discuss the role of MRI in the diagnosis
      and treatment plan.

PMID- 16284758
TI  - Comparable fMRI activity with differential behavioural performance on mental
      rotation and overt verbal fluency tasks in healthy men and women.
AB  - To explicate the neural correlates of sex differences in visuospatial and verbal
      fluency tasks, we examined behavioural performance and blood-oxygenation-level
      dependent (BOLD) regional brain activity, using functional magnetic resonance
      imaging, during a three-dimensional (3D) mental rotation task and a compressed
      sequence overt verbal fluency task in a group of healthy men (n=9) and women
      (n=10; tested during the low-oestrogen phase of the menstrual cycle). Men
      outperformed women on the mental rotation task, and women outperformed men on the
      verbal fluency task. For the mental rotation task, men and women activated areas
      in the right superior parietal lobe and the bilateral middle occipital gyrus in
      association with the rotation condition. In addition, men activated the left
      middle temporal gyrus and the right angular gyrus. For verbal fluency, men
      activated areas in the bilateral superior frontal gyrus, right cingulate gyrus,
      left precentral gyrus, left medial frontal gyrus, left inferior frontal gyrus,
      thalamus, left parahippocampal gyrus and bilateral lingual gyrus, and women
      activated areas in the bilateral inferior frontal gyrus and left caudate. Despite
      observing task related activation in the hypothesised areas in men and women, no
      areas significantly differentiated the two sexes. Our results demonstrate
      comparable brain activation in men and women in association with mental rotation
      and verbal fluency function with differential performance, and provide support
      for sex differences in brain-behaviour relationships.

PMID- 16284760
TI  - Lesions of the accessory parotid gland in children.
AB  - The accessory parotid gland, a little-known and seldom-mentioned anatomical
      variant, is a nodule of normal salivary tissue separate from the main parotid
      gland, located on the masseter muscle and connected to the Stensen duct at that
      level. It can be the site of both congenital and acquired lesions.

PMID- 16284761
TI  - Predicting outcome in term neonates with hypoxic-ischaemic encephalopathy using
      simplified MR criteria.
AB  - BACKGROUND: MRI is an established investigation in the evaluation of neonates
      with suspected hypoxic-ischaemic encephalopathy (HIE). However, its role as a
      predictor of neurodevelopmental outcome remains complex. OBJECTIVE: To establish
      reproducible simplified MR criteria and evaluate their role in predicting
      neurodevelopmental outcome in term neonates with HIE. MATERIALS AND METHODS: Term
      neonates with suspected HIE had MRI at 7-10 days of age. MR scans were
      interpreted according to new simplified criteria by two radiologists blinded to
      the clinical course and outcome. The new simplified criteria allocated grade 1 to
      cases with no central and less than 10% peripheral change, grade 2 to those with
      less than 30% central and/or 10-30% peripheral area change, and grade 3 to those
      with more than 30% central or peripheral change. MRI changes were compared with
      clinical neurodevelopmental outcome evaluated prospectively at 1 year of age.
      Neurodevelopmental outcome was based upon the DQ score (revised Griffith's) and
      cerebral palsy on neurological assessment. RESULTS: Of 20 subjects, all those
      showing severe (grade 3) MR changes (35%) died or had poor neurodevelopmental
      outcome. Subjects with a normal MR scan or with scans showing only mild (grade 1)
      MR changes (55%) had normal outcomes. One subject showing moderate (grade 2)
      changes on MRI had a moderate outcome (5%), while another had an atypical pattern
      of MR changes with a normal outcome (5%). CONCLUSIONS: Assessment of full-term
      neonates with suspected HIE using the simplified MR criteria is highly predictive
      of neurodevelopmental outcome.

PMID- 16284762
TI  - MR findings of complicated multifetal gestations.
AB  - This paper presents a review of various complications of multifetal gestations
      identified on MR imaging and highlights findings of those complications unique to
      monochorionic twinning. The goal is to illustrate the potential of MR as a useful
      application in these clinical circumstances. A total of 32 women with multifetal
      gestations and suspected complication detected initially by US underwent T2
      weighted MR imaging. Additional T1-weighted images were obtained when
      intracranial hemorrhage was suspected. MR and US findings were compared in all
      cases. Of 32 cases, six demonstrated fetal complications specific to
      monochorionic twinning; the findings consisted of conjoined twins (n=2), twin
      twin transfusion syndrome (n=1), co-twin demise with embolic disease (n=2), and
      twin-reversed arterial perfusion. (TRAP) syndrome (n=1). MR imaging confirmed US
      findings in all cases and was particularly helpful in delineating the extent of
      intracranial complications of monochorionic twins. The technique also showed
      improved anatomical detail in cases of conjoined twins. MR imaging provided
      additional information in cases of complicated monochorionic twinning, making it
      a useful complementary technique when combined with initial sonographic
      assessment.

PMID- 16284763
TI  - Neonatal hypoglycaemic encephalopathy: diffusion-weighted imaging and proton MR
      spectroscopy.
AB  - We report two infants with neonatal hypoglycaemic encephalopathy who were
      evaluated with diffusion-weighted imaging (DWI) and proton MR spectroscopy (MRS)
      as well as conventional MR. As in conventional MR, DWI and proton MRS revealed a
      predominance of abnormalities in the parieto-occipital lobes and underlying white
      matter including the splenium of the corpus callosum. In the acute phase of the
      disease, lesions on DWI showed restricted water diffusion and on DWI the
      characteristic lesions seemed to be more readily discernible than on conventional
      MRI. In the chronic phase, DWI demonstrated increased water diffusion in the
      affected areas showing atrophy on conventional MRI. Proton MRS revealed an
      increased lactate-lipid peak and a decreased NAA peak in the involved areas. DWI
      and proton MRS findings appear helpful in evaluating the extent and the presence
      of neuronal damage early in the course of neonatal hypoglycaemic encephalopathy.

PMID- 16284765
TI  - Study of optical properties of electropolymerized melanin films by
      photopyroelectric spectroscopy.
AB  - Photopyroelectric (PPE) spectroscopy, in the 350-1,075 nm wavelength range, was
      used to study the optical properties of electropolymerized melanin films on
      indium tin oxide (ITO) coated glass. The PPE intensity signal as a function of
      the wavelength lambda, V (n)(lambda) and its phase F (n)(lambda) were
      independently measured. Using the PPE signal intensity and the thermal and
      optical properties of the pyroelectric detector, we were able to calculate the
      optical absorption coefficient beta of melanin in the solid-state. We believe
      this to be the first such measurement of its kind on this material. Additionally,
      we found an optical gap in these melanin films at 1.70 eV.

PMID- 16284764
TI  - The portal vein in children: radiological review of congenital anomalies and
      acquired abnormalities.
AB  - A variety of portal vein anomalies that occur in children can be identified by
      US, CT, MRI and portal venography. Although these abnormalities can also occur in
      adults, there are certain pathological processes and aberrations within the
      portal system that are specific to children. Knowledge of the embryology and
      anatomy of the portal vein is of benefit in the understanding of these anomalies.
      Identifying deviations from normal portal architecture is important in the work
      up for surgery such as liver transplantation, and prior to interventional
      procedures such as stent placement or embolization. The aim of this paper is to
      summarize the various types of congenital and acquired portal vein abnormalities
      that occur in children, describe their radiological features and provide images
      to demonstrate the differences from normal portal venous anatomy.

PMID- 16284766
TI  - Intracortical chondroma: a report of two cases.
AB  - Intracortical chondromas are exceedingly rare lesions that have the
      histopathologic appearance of enchondromas, but are located within cortical bone.
      Two new cases of intracortical chondroma, one symptomatic and the other found
      incidentally, are presented and the entity's brief literature reviewed.

PMID- 16284767
TI  - MR appearance of autologous chondrocyte implantation in the knee: correlation
      with the knee features and clinical outcome.
AB  - OBJECTIVE: To relate the magnetic resonance imaging (MRI) appearance of
      autologous chondrocyte implantation (ACI) in the knee in the 1st postoperative
      year with other knee features on MRI and with clinical outcome. DESIGN AND
      METHODS: Forty-nine examinations were performed in 49 patients at 1 year after
      ACI in the knee. Forty-one preoperative magnetic resonance (MR) examinations were
      also available. The grafts were assessed for smoothness, thickness in comparison
      with that of adjacent cartilage, signal intensity, integration to underlying bone
      and adjacent cartilage, and congruity of subchondral bone. Presence of overgrowth
      and bone marrow appearance beneath the graft were also assessed. Presence of
      osteophyte formation, further cartilage defects, appearance of the cruciate
      ligaments and the menisci were also recorded. An overall graft score was
      constructed, using the graft appearances. This was correlated with the knee
      features and the Lysholm score, a clinical self-assessment score. The data were
      analysed by a Kruskal-Wallis H test followed by a Mann-Whitney U test with
      Bonferroni correction as post-hoc test. RESULTS: Of 49 grafts, 32 (65%)
      demonstrated complete defect filling 1 year postoperatively. General overgrowth
      was seen in eight grafts (16%), and partial overgrowth in 13 grafts (26%). Bone
      marrow change underneath the graft was seen; oedema was seen in 23 grafts (47%),
      cysts in six grafts (12%) and sclerosis in two grafts (4%). Mean graft score was
      8.7 (of maximal 12) (95% CI 8.0-9.5). Knees without osteophyte formation or
      additional other cartilage defects (other than the graft site) had a
      significantly higher graft score than knees with multiple osteophytes (P=0.0057)
      or multiple further cartilage defects (P=0.014). At 1 year follow-up improvement
      in the clinical scores was not significantly different for any subgroup. Knees
      with a graft score of 8 points or greater had a better improvement of the
      clinical score than those of 7 points or fewer. CONCLUSIONS: At 1 year follow-up
      after ACI, higher graft scores are associated with an overall better preserved
      knee joint. ACI improves the clinical outcome, but there is no statistically
      significant correlation of graft score and clinical outcome.

PMID- 16284768
TI  - Serum lipid profile in patients with systemic sclerosis: relationship to the
      thyreometabolic state.

PMID- 16284769
TI  - Possible association of the X-ray cross complementing gene 1 (XRCC1) Arg280His
      polymorphism as a risk for rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the
      invasion of synovial cells into cartilage and bone, exhibiting certain features
      of transformed cells. To examine whether retardation of DNA repair pathway of
      oxidative damage is a possible mechanism in altered phenotypes of these cells, we
      analyzed SNPs of the base excision repair (BER) protein, X-ray repair cross
      complementing gene 1 (XRCC1), among RA patients. Genomic DNA was extracted from
      blood cells of 40 RA patients and SNPs of the three allele of the XRCC1 coding
      region (codons 194, 280 and 399) were determined by PCR, followed by sequencing.
      Of the three polymorphisms, only the XRCC1 Arg280His allele was associated with
      increased RA risk (odds ratio 13; 95% confidence interval 1.1-147) after
      adjustment for smoking. These data provide evidence for the first time that BER,
      which is involved in the recovery from oxidative damage, may correlate with RA.

PMID- 16284770
TI  - Ferumoxtran-10-enhanced MR imaging of the bone marrow before and after
      conditioning therapy in patients with non-Hodgkin lymphomas.
AB  - To quantify permeability changes of the "blood-bone marrow barrier" (BMB) and to
      detect malignant bone marrow infiltrations before and after conditioning therapy
      for subsequent leukapheresis using ferumoxtran-10-enhanced magnetic resonance
      (MR) imaging. Twenty-two patients with malignant non-Hodgkin lymphomas (NHL),
      including 9 patients (group A) before and 13 patients (group B) after
      conditioning therapy, underwent MR of the spine before and after infusion of
      ferumoxtran-10 (0.045 mmol Fe/kg BW). Pulse sequences comprised dynamic T1-GE and
      pre- and post-contrast T1-SE and STIR sequences. Dynamic deltaSI-data were
      correlated with the quantity of mobilized CD34+ cells. In addition, the number of
      focal bone marrow lesions was compared before and after ferumoxtran-10
      administration. Dynamic deltaSI-data were higher in group B than in group A,
      indicating an increased BMB permeability after conditioning therapy. However,
      deltaSI-data did not correlate with the quantity of mobilized CD34+ cells.
      Ferumoxtran-10-enhanced STIR images demonstrated a significant signal decline of
      the normal, non-neoplastic bone marrow and a significantly increased detection of
      focal neoplastic lesions compared to pre-contrast images (P<0.05). Ferumoxtran-10
      depicted the bone marrow response to conditioning therapy by an increase in BMB
      permeability, which, however, did not correlate with the number of mobilized
      CD34+ cells. Ferumoxtran-10 improved the detection of focal bone marrow lesions
      significantly (P<0.05).

PMID- 16284771
TI  - Acquired lesions of the corpus callosum: MR imaging.
AB  - In this pictorial review, we illustrate acquired diseases or conditions of the
      corpus callosum that may be found by magnetic resonance (MR) imaging of the
      brain, including infarction, bleeding, diffuse axonal injury, multiple sclerosis,
      acute disseminated encephalomyelitis, Marchiafava-Bignami disease, glioblastoma,
      gliomatosis cerebri, lymphoma, metastasis, germinoma, infections, metabolic
      diseases, transient splenial lesion, dilated Virchow-Robin spaces, wallerian
      degeneration after hemispheric damage and focal splenial gliosis. MR imaging is
      useful for the detection and differential diagnosis of corpus callosal lesions.
      Due to the anatomical shape and location of the corpus callosum, both coronal and
      sagittal fluid-attenuated inversion recovery images are most useful for
      visualizing lesions of this structure.

PMID- 16284772
TI  - The influence of liquid crystal display (LCD) monitors on observer performance
      for the detection of nodular lesions on chest radiographs.
AB  - PURPOSE: To access the influence of liquid crystal display (LCD) monitors on the
      detectability of nodular lesions depicted on chest radiographs by comparing them
      with a high-resolution cathode ray tube (CRT) monitor. MATERIAL AND METHODS: Ten
      radiologists interpreted 247 soft-copy images on LCD monitors with pixel arrays
      of 1,024x1,280, 1,200x1,600, 1,536x2,048 and 2,048x2,560, and a CRT monitor with
      a pixel array of 2,048x2,560, and were asked to indicate their individual
      confidence levels regarding the presence of a nodule. These images were chest
      radiographs with and without a lung nodule from the "Standard Digital Image
      Database" created by the Japanese Society of Radiological Technology. The
      luminance distributions of all monitors were adjusted to the same, and the
      ambient illumination was 200 lux. Observer performance was analyzed in terms of
      the receiver-operating characteristics. RESULTS: No significant statistical
      differences in nodule detection performance were found among the four LCD
      monitors and the CRT monitor. CONCLUSION: The nodule detection performance on the
      LCD monitors with a spatial resolution higher than a matrix size of 1,024x1,280
      was found to be equivalent to that on the high-resolution CRT monitor.

PMID- 16284773
TI  - Cost-benefit analysis of screening colonoscopy in 40- to 50-year-old first-degree
      relatives of patients with colorectal cancer.
AB  - BACKGROUND AND AIMS: As shown previously, 40- to 50-year-old first-degree
      relatives of patients with colorectal cancer (CRC) have significantly more
      colorectal adenomas than controls of the same age. Screening colonoscopy of these
      persons at risk between 40 and 50 years might be cost beneficial. METHODS: We
      prepared a detailed cost-benefit analysis of screening colonoscopy and possible
      repeat endoscopies according to current expenditures for endoscopic procedures in
      Germany. Since screening colonoscopy is generally offered and reimbursed from 55
      years on in Germany, we analysed the period between 45 and 55 years, taking an
      annual interest rate of 5% into account. Costs were analysed based on the results
      of a former study [11] depending on various participation rates in a general
      screening programme. FINDINGS: Based on the available 1994 figure of about 20,000
      euros for diagnosis and treatment of one cancer case, screening colonoscopy is
      cost beneficial when participation is high. Under a more realistic assumption of
      currently about 40,000 euros per cancer case, screening colonoscopy is cost
      beneficial in any case. INTERPRETATION: Our data support that systematic
      screening colonoscopy in first-degree relatives of patients with CRC by the age
      of 45 years most likely demonstrates an economic benefit.

PMID- 16284774
TI  - Nanostructure of specific chromatin regions and nuclear complexes.
AB  - Spatially modulated illumination (SMI) microscopy is a method of widefield
      fluorescence microscopy featuring interferometric illumination, which delivers
      structural information about nanoscale features in fluorescently labeled cells.
      Using this approach, structural changes in the context of gene activation and
      chromatin remodeling may be revealed. In this paper we present the application of
      SMI microscopy to size measurements of the 7q22 gene region, giving us a size
      estimate of 105+/-16 nm which corresponds to an average compaction ratio of
      1:324. The results for the 7q22 domain are compared with the previously measured
      sizes of other fluorescently labeled gene regions, and to those obtained for
      transcription factories. The absence of a correlation between the measured and
      genomic sizes of the various gene regions indicate that a high variability in
      chromatin folding is present, with factors other than the sequence length
      contributing to the chromatin compaction. Measurements of the 7q22 region in
      different preparations and at different excitation wavelengths show a good
      agreement, thus demonstrating that the technique is robust when applied to
      biological samples.

PMID- 16284775
TI  - From analog to digital: exploring cell dynamics with single quantum dots.
AB  - Semiconductor quantum dots (QDs) have emerged as new fluorescent probes for
      biology. When combined with ultrasensitive optical techniques, they allow motions
      of individual biomolecules to be tracked in live cells with high signal-to-noise
      and over unprecedented durations. Single QD imaging readily offers a powerful
      tool to investigate the organization in cell membranes. Altogether QDs will
      contribute to more advanced biological imaging and enable new studies on the
      dynamics of cellular processes.

PMID- 16284776
TI  - Two cell wall associated peroxidases from Arabidopsis influence root elongation.
AB  - Two class III peroxidases from Arabidopsis, AtPrx33 and Atprx34, have been
      studied in this paper. Their encoding genes are mainly expressed in roots;
      AtPrx33 transcripts were also found in leaves and stems. Light activates the
      expression of both genes in seedlings. Transformed seedlings producing AtPrx33
      GFP or AtPrx34-GFP fusion proteins under the control of the CaMV 35S promoter
      exhibit fluorescence in the cell walls of roots, showing that the two peroxidases
      are localized in the apoplast, which is in line with their affinity for the
      Ca(2+)-pectate structure. The role they can play in cell wall was investigated
      using (1) insertion mutants that have suppressed or reduced expression of AtPrx33
      or AtPrx34 genes, respectively, (2) a double mutant with no AtPrx33 and a reduced
      level of Atprx34 transcripts, (3) a mutant overexpressing AtPrx34 under the
      control of the CaMV 35S promoter. The major phenotypic consequences of these
      genetic manipulations were observed on the variation of the length of seedling
      roots. Seedlings lacking AtPrx33 transcripts have shorter roots than the wild
      type controls and roots are still shorter in the double mutant. Seedlings
      overexpressing AtPrx34 exhibit significantly longer roots. These modifications of
      root length are accompanied by corresponding changes of cell length. The results
      suggest that AtPrx33 and Atprx34, two highly homologous Arabidopsis peroxidases,
      are involved in the reactions that promote cell elongation and that this occurs
      most likely within cell walls.

PMID- 16284777
TI  - Loss of stability, pH, and the anisotropic extensibility of Chara cell walls.
AB  - We investigated the effects of acid conditions on the extensibility of isolated
      wall segments from growing Chara corallina cells, providing the first detailed
      multi-azimuthal description of the anisotropic elastic modulus of the walls. The
      values of anisotropic modulus were obtained by loading a tensile force on wall
      ribbons excised from the cell walls along twelve different azimuths, and
      measuring the resulting elongation of the ribbons. Our study differs from
      previous studies in which mechanical loading of the wall materials was performed
      under creep conditions. We used ramp-loading conditions which meet the
      requirements for Loss of Stability. The results show that whereas a linear
      relationship between wall extension and log time is typical for creep-based
      experiments, it is not seen under ramp-loading conditions. To clarify the
      relative values of the wall moduli, the complete all-around anisotropic modulus
      is presented in polar coordinates, with the value of longitudinal modulus
      normalized to one unit. Acid pH enhances the extensibility of the wall materials,
      especially when medium pH<or=4, indicating that it is necessary to eliminate the
      prolonged plastic extension in order to obtain meaningful modulus values of wall
      materials immersed in acid environments.

PMID- 16284778
TI  - Class-1 hemoglobin and antioxidant metabolism in alfalfa roots.
AB  - In the course of nitric oxide (NO) scavenging, hemoglobin (Hb) turnover is linked
      to antioxidant metabolism and affects the cellular redox level. The influence of
      Hb presence on the ascorbate-glutathione cycle enzymes and the levels of H(2)O(2)
      and ascorbate was investigated in alfalfa root cultures transformed to over
      express (Hb+) or down-regulate (Hb-) class-1 Hb. Hb+ lines had substantially
      increased ascorbate levels as well as elevated monodehydroascorbate reductase and
      ascorbate peroxidase activities. Hb- lines showed significant increases in
      dehydroascorbate reductase and glutathione reductase activities. The observed
      changes in ascorbate and ascorbate-glutathione cycle enzymes were pronounced both
      at high (40 kPa) and low (3 kPa) O(2) pressures. Hb- lines had significantly
      reduced levels of the NO- and H(2)O(2)-sensitive enzyme, aconitase, as compared
      to Hb+ lines. This reduced activity was likely due the higher levels of NO in Hb-
      lines, as treatment of plant extracts with the NO-donor DEANO also affected
      aconitase activity. The H(2)O(2) levels were not significantly different amongst
      the lines and showed no variation with change in oxygen partial pressure. In
      conclusion, the expression of class-1 Hb improves the antioxidant status through
      increased ascorbate levels and increased activity of enzymes involved in H(2)O(2)
      removal.

PMID- 16284780
TI  - Generation or birth cohort effect on cancer risk in Li-Fraumeni syndrome.
AB  - Genetic anticipation is the increased incidence, earlier onset, or increased
      severity of a disease in successive generations. Before the biological basis of
      anticipation had been demonstrated, the phenomenon was thought to be due to
      sampling bias, epigenetic effects, gene conversion, or recombinant events. Since
      then, the biologic basis for anticipation in a number of neurodegenerative
      disorders has been shown to be attributable to trinucleotide repeat instability,
      with expansion of repeats clearly correlated with an earlier age of onset.
      Recently, telomere shortening has been suggested as the mechanism for
      anticipation in the autosomal dominant form of dyskeratosis congenita,
      attributable to mutations in the TERC gene, leading to dysfunctional telomeres
      (Vulliamy et al. 2004). However, the pattern of anticipation has been observed in
      other disorders, including cancers, for which no genetic defect has been
      identified. In this study, we assess the apparent generation effect on cancer
      incidence in ten extended families with P53 germline mutation, identified through
      probands diagnosed with childhood sarcoma. The probands were from two sets of
      systematically ascertained sarcoma patients treated at the University of Texas M.
      D. Anderson Cancer Center between 1944 and 1982. From those overall studies, we
      have identified ten kindreds having germline P53 mutations in more than one
      generation. We compared the cancer incidence in members of successive generations
      of these families with P53 mutations (carriers) and with no P53 mutations
      (noncarriers). In carriers, cancer incidence increased in succeeding generations;
      there was no evidence for this effect in noncarriers; however, the noncarrier
      population was too small to rule it out. The apparent lack of increase in
      incidence in noncarriers argues against a cohort effect explaining the increase
      in carriers.

PMID- 16284779
TI  - Prevalence and genetic diversity of Entamoeba histolytica in an institution for
      the mentally retarded in the Philippines.
AB  - A total of 113 mentally retarded patients residing in a mental institution in
      Metropolitan Manila, Philippines, were screened for the presence of Entamoeba
      histolytica based on microscopy and polymerase chain reaction (PCR). Anti-E.
      histolytica antibodies were also screened in 97 serum samples collected using
      immunofluorescence antibody (IFA) test. Parasitological examination showed E.
      histolytica/Entamoeba dispar in 43 cases (38.05%), while PCR detected 74 cases
      (65.48%) positive for E. histolytica and 6 cases (5.30%) positive for E. dispar.
      Interestingly, these 6 samples were coinfected with E. histolytica. IFA test
      revealed that 80.41% (78/97) of the respondents possessed significant antibody
      titers for intestinal infection of E. histolytica. Of this number, there were 5
      patients negative in IFA test but positive in PCR. The genetic diversity of E.
      histolytica isolates was also investigated by analyzing polymorphism in the
      serine-rich gene by nested PCR on DNA directly extracted from stool specimens. A
      combination of the nested PCR results and the AluI digestion of the PCR products
      examined yielded six distinct DNA banding patterns among the 74 stool isolates.
      An apparent clustering of E. histolytica strains was observed in patients living
      in different residential cottages of the institution. These results indicate the
      high prevalence of E. histolytica in an institution for the mentally retarded in
      the Philippines.

PMID- 16284781
TI  - Enzymatic synthesis of L-ascorbyl linoleate in organic media.
AB  - A novel L-ascorbyl fatty acid ester, L-ascorbyl linoleate was successfully
      prepared by enzymatic esterification and transesterification in a non-aqueous
      medium using immobilized lipase as biocatalyst. Changes in enzymatic activity and
      product yield were studied for the following variable: the nature of the fatty
      acid, the fatty acid concentration and water content. The yield of synthesis for
      the C18 unsaturated fatty acids were higher than for the C18 saturated fatty
      acid. Initial enzyme concentration does not affect the equilibrium of the
      reaction. And the product yield (33.5%) in the transesterification was higher
      than that of the esterification (21.8%) at a high-substrate concentration 0.3 M.
      The medium water content was found to have a distinct influence on the L-ascorbyl
      linoleate synthesis.

PMID- 16284782
TI  - Twenty years of research on community composition and species distribution of
      arbuscular mycorrhizal fungi in China: a review.
AB  - The biodiversity and distribution of arbuscular mycorrhizal fungi (AMF) in
      different ecosystems and plant communities in China has received increasing
      interest over the past decades. This has led to a steady increase in the number
      of scientific papers published on this topic. Studies have surveyed AMF
      colonizing rhizospheres of most families of angiosperms, bryophytes,
      pteridophytes, and gymnosperms. China has about 30,000 plant species (one eighth
      of the plant species worldwide). A total of 104 AMF species within nine genera,
      including 12 new species, have been reported in environments such as croplands,
      grasslands, forests, and numerous disturbed environments. In this paper, we
      review data published over the past 20 years on AMF community composition and
      species distribution, the mycorrhizal status of plants, AMF spore communities in
      different habitats, and germplasm collections in China. Possible future trends in
      the study of the biodiversity of AMF are also briefly discussed. In particular,
      the aim of our review is to make some of the recent work published in the Chinese
      literature accessible to a wider international audience.

PMID- 16284783
TI  - Topiramate augments the antipsychotic-like effect and cortical dopamine output of
      raclopride.
AB  - Recent clinical studies have shown that the anticonvulsant drug topiramate may
      improve negative symptoms in schizophrenia when added to a stable regimen of
      neuroleptic medication. It has also been shown that addition of topiramate to
      neuroleptics might be beneficial in treatment-resistant schizophrenia. Clinically
      effective doses of antipsychotic drugs (APDs) have been found to suppress
      conditioned avoidance response behavior (CAR), a preclinical test of
      antipsychotic activity with high predictive validity, in rats. Therefore, we
      investigated the putative antipsychotic-like activity of topiramate when added to
      the selective dopamine (DA) D2 receptor antagonist raclopride, using the CAR
      model in the rat. Extrapyramidal side effect liability of the drug combination
      was evaluated in parallel by means of the catalepsy test. We also examined the
      effect of this drug treatment on DA release in the medial prefrontal cortex
      (mPFC) and the nucleus accumbens (NAC), using in vivo microdialysis in freely
      moving animals. Topiramate (40 mg/kg), while ineffective when given alone,
      significantly augmented the antipsychotic-like effect of raclopride (0.075 mg/kg)
      on CAR without any concomitant catalepsy. Addition of topiramate to rats treated
      with raclopride generated a large increase in DA output in the mPFC, whereas no
      additional effect on the raclopride-induced DA release in the NAC was obtained.
      These data support the adjunctive use of topiramate in schizophrenia to
      ameliorate negative symptoms and suggest that this treatment may increase the
      efficacy, but not the extrapyramidal side effect liability, of the APDs used.

PMID- 16284784
TI  - Long-term anti-kindling effects of desynchronizing brain stimulation: a
      theoretical study.
AB  - In a modeling study we show that desynchronization stimulation may have powerful
      anti-kindling effects. For this, we incorporate spike-timing-dependent plasticity
      into a generic network of coupled phase oscillators, which serves as a model
      network of synaptically interacting neurons. Two states may coexist under
      spontaneous conditions: a state of uncorrelated firing and a state of
      pathological synchrony. Appropriate stimulation protocols make the network learn
      or unlearn the pathological synaptic interactions, respectively. Low-frequency
      periodic pulse train stimulation causes a kindling. Permanent high-frequency
      stimulation, used as golden standard for deep brain stimulation in medically
      refractory movement disorders, basically freezes the synaptic weights. In
      contrast, desynchronization stimulation, e.g., by means of a multi-site
      coordinated reset, has powerful long-term anti-kindling effects and enables the
      network to unlearn pathologically strong synaptic interactions. We propose
      desynchronization stimulation for the therapy of movement disorders and
      epilepsies.

PMID- 16284785
TI  - The critical power and related whole-body bioenergetic models.
AB  - This paper takes a performance-based approach to review the broad expanse of
      literature relating to whole-body models of human bioenergetics. It begins with
      an examination of the critical power model and its assumptions. Although
      remarkably robust, this model has a number of shortcomings. Attention to these
      has led to the development of more realistic and more detailed derivatives of the
      critical power model. The mathematical solutions to and associated behaviour of
      these models when subjected to imposed "exercise" can be applied as a means of
      gaining a deeper understanding of the bioenergetics of human exercise
      performance.

PMID- 16284786
TI  - Regular endurance training reduces the exercise induced HIF-1alpha and HIF-2alpha
      mRNA expression in human skeletal muscle in normoxic conditions.
AB  - Regular exercise induces a variety of adaptive responses that enhance the
      oxidative and metabolic capacity of human skeletal muscle. Although the
      physiological adjustments of regular exercise have been known for decades, the
      underlying mechanisms are still unclear. The hypoxia inducible factors 1 and 2
      (HIFs) are clearly related heterodimeric transcription factors that consist of an
      oxygen-depended alpha-subunit and a constitutive beta-subunit. With hypoxic
      exposure, HIF-1alpha and HIF-2alpha protein are stabilized. Upon
      heterodimerization, HIFs induce the transcription of a variety of genes including
      erythropoietin (EPO), transferrin and its receptor, as well as vascular
      endothelial growth factor (VEGF) and its receptor. Considering that several of
      these genes are also induced with exercise, we tested the hypothesis that the
      mRNA level of HIF-1alpha and HIF-2alpha subunits increases with a single exercise
      bout, and that this response is blunted with training. We obtained muscle
      biopsies from a trained (5 days/week during 4 weeks) and untrained leg from the
      same human subject before, immediately after, and during the recovery from a 3 h
      two-legged knee extensor exercise bout, where the two legs exercised at the same
      absolute workload. In the untrained leg, the exercise bout induced an increase
      (P<0.05) in HIF-1alpha fold and HIF-2alpha fold mRNA at 6 h of recovery. In
      contrast, HIF-1alpha and HIF-2alpha mRNA levels were not altered at any time
      point in the trained leg. Obviously, HIF-1alpha and HIF-2alpha mRNA levels are
      transiently increased in untrained human skeletal muscle in response to an acute
      exercise bout, but this response is blunted after exercise training. We propose
      that HIFs expression is upregulated with exercise and that it may be an important
      transcription factor that regulates adaptive gene responses to exercise.

PMID- 16284787
TI  - Effect of concentric or eccentric weight training on the expression of heat shock
      proteins in m. biceps brachii of very well trained males.
AB  - Increased HSP expression in response to acute exercise is well documented in
      animal studies, and there is growing evidence that similar responses occur in
      man. In general, many human exercise studies have investigated the HSP response
      to low force continuous activity, while the knowledge about the HSP response to
      high force intermittent type of activity, like weight training, is so far sparse.
      In addition, most studies have used untrained subjects, and a common observation
      is that acute low force continuous activity in untrained individuals increases
      the HSP expression in these individuals. The main scope of this study was to
      investigate the HSP response in very well trained males subjected to longitudinal
      high intensity exercise, and if this response was dependent on exercise modality
      [i.e. eccentric (ECC) or concentric (CON) contractions]. Very well trained males
      performed progressive strength training consisting of either high force ECC or
      high force CON elbow flexions 2-3 times a week for 12 weeks. Compared with pre
      exercise levels, HSP72 expression decreased by 46.1% (P<0.05) after CON
      contractions. GRP75 expression was unchanged after ECC or CON contractions, while
      ubiquitin expression decreased by 19.9% (P<0.02) after ECC contractions. These
      findings imply that chronic, intensive exercise may attenuate the HSP response in
      well-trained males.

PMID- 16284788
TI  - Enhanced cerebral CO2 reactivity during strenuous exercise in man.
AB  - Light and moderate exercise elevates the regional cerebral blood flow by
      approximately 20% as determined by ultrasound Doppler sonography (middle cerebral
      artery mean flow velocity; MCA V(mean)). However, strenuous exercise, especially
      in the heat, appears to reduce MCA V(mean) more than can be accounted for by the
      reduction in the arterial CO(2) tension (P(a)CO(2)). This study evaluated whether
      the apparently large reduction in MCA V(mean) at the end of exhaustive exercise
      relates to an enhanced cerebrovascular CO(2) reactivity. The CO(2) reactivity was
      evaluated in six young healthy male subjects by the administration of CO(2) as
      well as by voluntary hypo- and hyperventilation at rest and during exercise with
      and without hyperthermia. At rest, P(a)CO(2) was 5.1 +/- 0.2 kPa (mean +/- SEM)
      and MCA V(mean) 50.7 +/- 3.8 cm s(-1) and the relationship between MCA V(mean)
      and P(a)CO(2 )was linear (double-log slope 1.1 +/- 0.1). However, the
      relationship became curvilinear during exercise (slope 1.8 +/- 0.1; P < 0.01 vs.
      rest) and during exercise with hyperthermia (slope 2.3 +/- 0.3; P < 0.05 vs.
      control exercise). Accordingly, the cerebral CO(2) reactivity increased from 30.5
      +/- 2.7% kPa(-1) at rest to 61.4 +/- 10.1% kPa(-1) during exercise with
      hyperthermia (P < 0.05). At exhaustion P(a)CO(2) decreased 1.1+/- 0.2 kPa during
      exercise with hyperthermia, which, with the determined cerebral CO(2) reactivity,
      accounted for the 28 +/- 10% decrease in MCA V(mean). The results suggest that
      during exercise changes in cerebral blood flow are dominated by the arterial
      carbon dioxide tension.

PMID- 16284789
TI  - Introducing a novel human mtDNA mutation into the Paracoccus denitrificans COX I
      gene explains functional deficits in a patient.
AB  - We identified a novel mutation (S142F) in the human mtDNA CO I gene in a patient
      with a clinical phenotype resembling mitochondrial cardioencephalomyopathy. To
      substantiate pathogenicity, we modeled the identified mutation in the homologous
      gene in Paracoccus denitrificans and analyzed the biochemical consequences. We
      observed a deleterious effect on enzyme activity, with a lack of heme a3. Taking
      advantage of the extensive structural homology between the bacterial enzyme and
      the mammalian core complex, we conclude that the novel S142F mutation is disease
      related. This approach can be used in other cases to support the pathogenicity of
      novel variants in the mitochondrial genome.

PMID- 16284790
TI  - Chemoprotection effect of retroviral vector encoding multidrug resistance 1 gene
      to allow intensified chemotherapy in vivo.
AB  - Increasing the expression of human multidrug resistance (MDR) 1 gene in bone
      marrow cells to prevent or circumvent bone morrow toxicity from chemotherapy
      agent is a high priority of dose intensification protocols. In this study, we
      have used a tumor-bearing model to investigate the chemoprotection effect of MDR1
      gene by transfecting retroviral vectors containing and expressing the MDR gene in
      vivo. Hematopoietic progenitor cells were served as target of MDR1 gene
      transferred by the mediation of retrovirus vector and engrafted into the BALB/c
      mice with 60Co-gamma ray exposure in advance. Doxorubicin (5, 10, and 20 mg/kg)
      suppressed tumor growth of the xenograft significantly in a dose-dependence mode
      if supported by suitable peripheral WBC. WBC count revealed that the mice that
      had received gene-transduced cells showed a significant increase in WBC count
      compared with their gene-transduced naive counterparts. The function and
      expression of MDR1 gene were detected by flow cytometry, RT-PCR, and
      immunohistochemistry (IC) method. MDRl mRNA expression could be detected in BM.
      Spleens contained measurable amounts of MDRl mRNA. Tail vein blood and tumor
      tissue detected MDRl DNA but no MDRl mRNA expression. FACS analysis of infected
      BM cells obtained 6 weeks later showed high levels of P-gp function. Based on
      these results we conclude that cytostatic drug resistance gene therapy may
      provide some degree of chemoprotection and so can increase the chemotherapy dose
      to kill tumor cells.

PMID- 16284792
TI  - The number of subsets required for OSEM reconstruction in nuclear cardiology.

PMID- 16284791
TI  - The role of NF-kappaB, IRF-1, and STAT-1alpha transcription factors in the iNOS
      gene induction by gliadin and IFN-gamma in RAW 264.7 macrophages.
AB  - Nitric oxide (NO) plays an important role in the pathogenesis of celiac disease.
      We have examined the involvement of nuclear factor-kappaB (NF-kappaB), interferon
      regulatory factor-1 (IRF-1), and signal transducer and activator of transcription
      1alpha (STAT-1alpha) on the synergistic induction of inducible nitric oxide
      synthase (iNOS) gene expression by gliadin (G) in association with interferon
      gamma (IFN-gamma) in RAW 264.7 macrophages. We found that IFN-gamma was efficient
      in enhancing the basal transcription of the iNOS promoter at 1, 6, and 24 h,
      whereas G had no effect. The G plus IFN-gamma association caused an increase in
      iNOS promoter activity which was inhibited by pyrrolidine dithiocarbammate (PDTC)
      at 6 and 24 h as well as by genistein (Gen) and tyrphostine B42 (TB42) at 1 h,
      inhibitors of NF-kappaB, IRF-1, and STAT-1alpha activation, respectively.
      Similarly, the IFN-gamma and G combination treatment led to a higher increase in
      iNOS mRNA levels at 1, 6, and 24 h compared with IFN-gamma alone. Gen and TB42
      inhibited iNOS mRNA levels at 1 h, whereas PDTC inhibited iNOS mRNA levels at 6
      and 24 h. In addition, the synergistic induction of iNOS gene expression by G
      plus IFN-gamma correlated with the induction of NF-kappaB, IRF-1, and STAT
      1alpha/DNA binding activity and mRNA expression. In conclusion, our study, which
      provides evidence that the effect of G on iNOS gene transcription in IFN-gamma
      stimulated RAW 264.7 cells can be ascribed to all three transcription factors,
      may contribute to lead to new insights into the molecular mechanisms governing
      the inflammatory process in celiac disease.

PMID- 16284793
TI  - Effects of ultraviolet B irradiation on the production of regulated upon
      activation normal T-cell expressed and secreted protein in cultured human
      epidermal keratinocytes.
AB  - The modulatory effects of ultraviolet B (UVB) irradiation on cutaneous
      inflammatory responses are well known but their mechanism remains obscure. It has
      been proposed that regulated upon activation normal T-cell expressed and secreted
      protein (RANTES), which is one of the chemokines produced by epidermal
      keratinocytes, might play an important role in the pathogenesis of cutaneous
      inflammatory disorders, such as atopic dermatitis and psoriasis vulgaris. This
      study was designed to determine whether UVB irradiation could affect the
      production of RANTES that is induced in cultured normal human epidermal
      keratinocytes upon stimulation by inflammatory cytokines. We measured levels of
      the transcript of the gene for RANTES in cultured keratinocytes and of RANTES
      itself in culture supernatants by semiquantitative reverse transcription and the
      polymerase chain reaction and by an enzyme-linked immunosorbant assay (ELISA),
      respectively. Neither the transcript nor RANTES itself was detected without prior
      stimulation of cells by tumor necrosis factor alpha (TNF-alpha) and/or interferon
      gamma (IFN-gamma) and production of RANTES was not induced by UVB (100 J/m2)
      irradiation alone. Cells were irradiated with UVB just before addition of TNF
      alpha and IFN-gamma to the medium and then cells and culture supernatants were
      harvested 12, 24, and 36 h later. In both irradiated and non-irradiated cells,
      RANTES mRNA was first detected at 12 h and the level increased subsequently.
      RANTES itself was detected at 24 h, with a higher level at 36 h. At all time
      points examined, UVB irradiation inhibited the production of RANTES mRNA and of
      the protein itself. These results suggest that suppression of the production of
      RANTES by epidermal keratinocytes might be involved in the modulatory effects of
      UVB irradiation on cutaneous inflammation.

PMID- 16284794
TI  - Retinoic acid rescues lung hypoplasia in nitrofen-induced hypoplastic foetal rat
      lung explants.
AB  - There is increasing evidence to suggest that the retinoid pathway is involved in
      the pathogenesis of congenital diaphragmatic hernia (CDH). We hypothesised that
      retinoids are involved in the pathogenesis of associated pulmonary hypoplasia in
      CDH and therefore designed this study to investigate the effects of retinoid acid
      on nitrofen-induced hypoplastic lungs. Pregnant rats were exposed to either olive
      oil or 100 mg nitrofen on day 9.5 of gestation. Foetal lungs were harvested on
      embryonic day 13.5 and were cultured for 96 h with or without exogenous retinoic
      acid (RA) (1 muM) added daily to the culture medium. Lungs were divided into four
      study groups: control (n=31); control + RA (n=19); nitrofen (n=19); and nitrofen
      + RA (n=12). Lung growth was assessed in each group by measuring branching
      morphogenesis, total DNA content and the proportion of proliferating cells
      stained by immunohistochemistry. One-way ANOVA test was used for statistical
      analysis. Retinoic acid significantly increased the growth of nitrofen-induced
      hypoplastic lungs, whilst growth of control lungs did not change. The number of
      lung buds and lung area of nitrofen-exposed hypoplastic lungs after 96 h of
      culture significantly increased after the addition of RA compared to the non
      treated hypoplastic lungs (25.75+/-6.47 vs 15.11+/-3.29 and 0.98+/-0.18 mm(2) vs
      0.65+/-0.13 mm(2), respectively; P<0.0001). Lung perimeter was also higher when
      RA was added to hypoplastic lungs compared to the non-treated ones, although it
      did not reach significance (12.51+/-2.53 mm vs 11.19+/-2.56 mm; P=0.17).
      Conversely, the addition of RA to control lungs did not affect the number of lung
      buds, lung area or lung perimeter after 96 h in culture compared to the non
      treated ones (31.28+/-4.66 vs 31.81+/-6.67; 1.29+/-0.18(2) vs 1.29+/-0.23 mm(2)
      and 18.47+/-3.47 mm vs 17.89+/-2.94 mm, respectively; P=NS). Retinoic acid also
      increased the total DNA content and the proportion of proliferating cells in
      hypoplastic lungs compared to the non-treated ones (2.59+/-0.58 mug vs 1.96+/
      0.31 mug and 57.89+/-9.46% vs 36.76+/-8.15%, respectively; P<0.001). The addition
      of RA did not affect either total DNA content or the proportion of proliferating
      cells in control lungs compared to the non-treated ones (4.04+/-0.64 mug vs
      3.79+/-0.85 mug and 58.67+/-11.23% vs 56.03+/-10.36%, respectively; P=NS). This
      study demonstrates for the first time that RA rescues lung hypoplasia in nitrofen
      induced hypoplastic lungs. These results suggest that retinoid pathway may be
      involved in the pathogenesis of associated pulmonary hypoplasia in CDH.

PMID- 16284796
TI  - Effects of somatostatin prophylaxis after pylorus-preserving
      pancreaticoduodenectomy: increased delayed gastric emptying and reduced plasma
      motilin.
AB  - Somatostatin inhibits gastroenteropancreatic exocrine secretion and is often used
      after pancreaticoduodenectomy to reduce pancreatic secretion to minimize tissue
      damage and pancreatic stump complications. Because our earlier clinical work saw
      a major increase in delayed gastric emptying (DGE) with somatostatin prophylaxis
      after pylorus-preserving pancreaticoduodenectomy (PPPD), this small-group study
      was designed to confirm or disprove that observation. From August 1997 to
      December 2000, a total of 23 post-PPPD patients were randomized to receive
      somatostatin prophylaxis [somatostain (+)] (n = 11) or not [somatostatin] (-) (n
      = 12). The incidence of DGE, scintographic solid-phase emptying results on day 14
      postoperatively, and sequential fasting plasma motilin levels were compared, as
      motilin levels are related to both gastric motility and somatostatin levels. The
      somatostatin(+) group exhibited greatly increased patient complaints of DGE: 9 of
      11 (82%) versus 3 of 12 (25%) in the somatostatin(-) group. Radiologic
      scintography showed somatostatin prophylaxis prolonged the half-time (T(1/2)) of
      solid-phase emptying: 144.5 +/- 51.4 minutes for somatostatin(+) versus 89.0 +/-
      59.9 minutes for somatostatin(-) (p < 0.001). Comparing pre-PPPD and post-PPPD
      plasma motilin levels prior to somatostatin infusion, motilin decreased 80% in
      reaction to the surgery. For somatostatin(-) patients, motilin levels oscillated,
      or "rang," postoperatively, reaching a higher level on day 3, declined to a new
      record minimum on day 7, and by day 21 were 50% of the original and the slope of
      the recovery curve was increasing well. In somatostatin(+) patients the same
      ringing pattern was observed but decreased with motilin levels 30% to 70% lower
      than in the somatostatin(-) patients. By day 21 somatostatin(+) motilin levels
      were recovering but still only 20% original levels, and the slope of the recovery
      curve was not optimistic. On postoperative day 14 the plasma motilin levels
      (below approximately 6 bg/ml) correlated strongly with DGE for both groups.
      Despite the small sample size, the results indicated that (1) somatostatin
      prophylaxis significantly decreases fasting plasma motilin; (2) somatostatin
      prophylaxis produces lingering suppression of plasma motilin; (3) PPPD surgery
      itself significantly reduces fasting motilin levels with recovery to 50% normal
      at day 21; (4) the mechanism of somatostatin-induced DGE seems related to reduced
      fasting plasma motilin levels.

PMID- 16284797
TI  - HCOP: the HGNC comparison of orthology predictions search tool.
AB  - The HGNC Comparison of Orthology Predictions search tool, HCOP
      (http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/hcop.pl ), enables users to
      compare predicted human and mouse orthologs for a specified gene, or set of
      genes, from either species according to the ortholog assertions from the Ensembl,
      HGNC, Homologene, Inparanoid, MGI and PhIGs databases. Users can assess the
      reliability of the prediction from the number of these different sources that
      identify a particular orthologous pair. HCOP provides a useful one-stop resource
      to summarise, compare and access various sources of human and mouse orthology
      data.

PMID- 16284798
TI  - Implementation of the modified-SHIRPA protocol for screening of dominant
      phenotypes in a large-scale ENU mutagenesis program.
AB  - SHIRPA is a three-stage protocol for the comprehensive assessment of primarily
      mouse behavior. The first stage consists of high-throughput phenotyping of 33
      behavioral observations and 7 metabolic or disease observations. We modified this
      part of the protocol by integrating new morphologic observations into the initial
      phenotype assay of behavior and dysmorphology. Behavioral observations assessed
      by this protocol, now referred to as the "modified-SHIRPA," are compatible with
      the original "SHIRPA" protocol. Using modified-SHIRPA, we screened dominant
      phenotypes of more than 10,000 G(1) progeny generated by crossing DBA/2J females
      with ENU-treated C57BL/6J males. To date, we have obtained 136 hereditary
      confirmed mutants that exhibit behavioral and morphologic defects. Some
      independent mutant lines exhibited similar phenotypes, suggesting that they may
      represent alleles of the same gene or mutations in the same genetic pathway. They
      could hold great potential for the unraveling of the molecular mechanisms of
      certain phenotypes.

PMID- 16284799
TI  - Transgenic rescue of the mouse t complex haplolethal locus Thl1.
AB  - Chromosomal deletions can uncover haploinsufficient or imprinted regions of the
      genome. Previously, the haploinsufficient locus t haplolethal 1 (Thl1) was
      identified and localized to a 1.3-Mb region using overlapping deletions around
      the Sod2 and D17Leh94 loci of the mouse t complex on Chr 17. Germline chimeric
      mice, produced from embryonic stem (ES) cells containing radiation-induced
      deletions of the Thl1 locus, never produced viable deletion-bearing progeny when
      mated to C57BL/6J (B6) females. However, deletion-bearing offspring could be
      obtained by mating to females of other strains. In this article we describe a
      transgenic approach to narrow the critical region for Thl1. BAC clones were
      introduced into a deletion-bearing ES cell line and one was shown to rescue the
      Thl1 phenotype, reducing the critical region to 140 kb. Analysis of the gene
      content of this region suggests two strong Thl1 candidates, Pdcd2 and a novel SET
      domain-containing gene termed Tset1. A more detailed analysis using mice carrying
      overlapping deletions identified subregions that influence the phenotypic
      characteristics of Thl1 hemizygotes.

PMID- 16284800
TI  - A 191-kb genomic fragment containing the human alpha-globin locus can rescue
      alpha-thalassemic mice.
AB  - A 191-kb human bacterial artificial chromosome (BAC) containing the human alpha
      globin genomic locus was used to generate transgenic mice that express,
      exclusively, human alpha-globin ((hu)alpha-globin). Expression of (hu)alpha
      globin reaches a level of 36% of that of endogenous mouse alpha-globin ((mu)alpha
      globin) on a heterozygous mouse alpha-thalassemia background ((mu)alpha-globin
      knockout, (mu)alpha(+/-)). Hemizygous transgenic mice carrying the (hu)alpha
      globin locus on a heterozygous knockout background ((hu)alpha(+/0), (mu)alpha(++/
      -)) demonstrated complementation of most hematologic parameters. By crossing
      (hu)alpha(+/0), (mu)alpha(++/--) mice, we were able to generate mice entirely
      dependent on (hu)alpha-globin synthesis. Breeding and fluorescent in situ
      hybridization studies demonstrate that only mice homozygous for the transgene
      were able to rescue embryonic lethal homozygous (mu)alpha-globin knockout embryos
      ((mu)alpha(--/--)). Adult rescued mice produce hemoglobin at levels similar to
      wild-type mice, with partial red cell complementation based on mean corpuscular
      volume (MCV), mean corpuscular hemoglobin (MCH), and red cell distribution width
      (RDW) measurements. Significant erythrocythemia above wild-type levels seems to
      be the main compensatory mechanism for the normalization of the hemoglobin levels
      in the rescued animals. Our studies demonstrate that the (hu)alpha-globin locus
      in the 191-kb transgene contains all the necessary elements for the regulated
      expression of (hu)alpha-globin in transgenic mice. This animal model should be
      valuable for studying the mechanisms regulating (hu)alpha-globin production and
      for development of therapeutic strategies for beta-thalassemia based on
      downregulation of alpha-globin expression.

PMID- 16284801
TI  - Genetic mapping of Eutr1, a locus controlling E2-induced pyometritis in the Brown
      Norway rat, to RNO5.
AB  - In certain rat strains, chronic estrogen administration can lead to pyometritis,
      an inflammation of the uterus accompanied by infection and the accumulation of
      intraluminal pus. In this article, we report that the Brown Norway (BN) rat is
      highly susceptible to pyometritis induced by 17beta-estradiol (E2). The
      susceptibility of the BN rat to E2-induced pyometritis appears to segregate as a
      recessive trait in crosses to the resistant August x Copenhagen Irish (ACI)
      strain. In a (BN x ACI)F(2) population, we find strong evidence for a major
      genetic determinant of susceptibility to E2-induced pyometritis on rat chromosome
      5 (RNO5). Our data are most consistent with a model in which the BN allele of
      this locus, designated Eutr1 (Estrogen-induced uterine response 1), acts in an
      incompletely dominant manner to control E2-induced pyometritis. Furthermore, we
      have confirmed the contribution of Eutr1 to E2-induced uterine pyometritis using
      an RNO5 congenic rat strain. In addition to Eutr1, we obtained evidence
      suggestive of linkage for five additional loci on RNO2, 4, 11, 17, and X that
      control susceptibility to E2-induced pyometritis in the (BN x ACI)F(2)
      population.

PMID- 16284802
TI  - Localization of Eutr2, a locus controlling susceptibility to DES-induced uterine
      inflammation and pyometritis, to RNO5 using a congenic rat strain.
AB  - In some rat strains chronic administration of exogenous estrogens induces
      pyometritis, an inflammation of the uterus associated with infection, suggesting
      that there is genetic variation in susceptibility to estrogen-induced
      inflammation and pyometritis. In this article we report that following 10 weeks
      of treatment with the synthetic estrogen diethylstilbestrol (DES), Fisher 344
      (F344) rats exhibit modest uterine inflammation and a 0% incidence of
      pyometritis. By contrast, under identical experimental conditions, Brown Norway
      (BN) rats exhibit significant inflammation and a 100% incidence of pyometritis.
      Similarly, we also observed profound uterine inflammation and a 100% incidence of
      pyometritis in a congenic rat strain in which a segment of RNO5 from the BN
      strain is carried on the F344 strain. These data suggest that a locus on RNO5
      controls both the magnitude of DES-induced uterine inflammation and
      susceptibility to DES-induced pyometritis. This locus, designated Eutr2, resides
      within the same segment of RNO5 as the Eutr1 locus, which confers susceptibility
      to E2-induced pyometritis in an F2 population generated in a cross between the BN
      and August x Copenhagen 9935, Irish (ACI) strains.

PMID- 16284803
TI  - Cloning and expression of bovine glucose transporter GLUT12.
AB  - GLUT12 is a new member of facilitative glucose transporters. It was originally
      cloned from a human breast cancer cell line and its expression has been detected
      in rat mammary gland. Glucose transport across the plasma membrane of mammary
      epithelial cells is a rate-limiting factor in milk production. To examine
      GLUT12's expression and facilitate the study of GLUT12's potential role in
      supporting milk synthesis in lactating bovine mammary gland, we cloned bovine
      GLUT12 and examined its distribution of mRNA expression in bovine tissues. The
      full-length mRNA of bGLUT12 is 2,423 base pairs long and is predicted to encode a
      protein of 621 amino acids with a molecular weight of approximately 67 kDa. The
      deduced amino acid sequence of bovine GLUT12 is 87% and 82% identical to the
      sequences of human and mouse GLUT12. The sequence of bGLUT12 contains several
      characteristically conserved sugar transporter family signatures. Analysis of
      current bovine genomic data indicates that bovine GLUT12 gene consists of five
      exons. The major in vitro transcription and translation product of bovine GLUT12
      cDNA migrated at an apparent molecular weight of 41 kDa. In the presence of
      canine microsomal membranes, the translation product increased to 43 kDa,
      suggesting glycosylation. GLUT12 mRNA was found in all bovine tissues examined,
      but most abundant in bovine spleen and skeletal muscle, at intermediate levels in
      bovine kidney, testes, and mammary gland, and at lower levels in bovine liver,
      lung and intestine. Immunofluorescence staining showed that, in the presence of
      insulin, bGLUT12 is mainly distributed in the cytoplasm of the transiently
      transfected MAC-T bovine mammary epithelial cells.

PMID- 16284804
TI  - DNA polymorphisms of the prion doppel gene region in four different German cattle
      breeds and cows tested positive for bovine spongiform encephalopathy.
AB  - Polymorphisms of the prion protein gene PRNP have been shown to influence the
      susceptibility/resistance to prion infections in human and sheep. In addition,
      the T174M polymorphism within the flanking prion doppel gene (PRND) was thought
      to be involved in susceptibility to sporadic Creutzfeldt-Jacob disease. To study
      a possible influence of DNA polymorphisms of the bovine PRND gene in bovine
      spongiform encephalopathy (BSE), previously identified and newly isolated DNA
      polymorphisms were genotyped in all available German cattle that tested positive
      for BSE. Genotypes and calculated haplotypes were compared with breeding bulls
      serving as controls. Analysis of the four major breeds Schwarzbunt (Holstein
      Friesian), Rotbunt (Holstein Red), Fleckvieh (Simmental), and Braunvieh (Swiss
      Brown) resulted in the isolation of the previously known polymorphisms R50H and
      R132Q and two novel synonymous single nucleotide polymorphisms (SNPs) C4820T and
      A5063T. Comparative genotype and haplotype analysis of BSE and control animals
      revealed a significantly different distribution of polymorphisms C4815T and R132Q
      in Fleckvieh animals but not in the other breeds tested. No association to BSE
      susceptibility was detectable for polymorphisms R50H and A5063T.

PMID- 16284805
TI  - Exon skipping in the KIT gene causes a Sabino spotting pattern in horses.
AB  - Sabino (SB) is a white spotting pattern in the horse characterized by white
      patches on the face, lower legs, or belly, and interspersed white hairs on the
      midsection. Based on comparable phenotypes in humans and pigs, the KIT gene was
      investigated as the origin of the Sabino phenotype. In this article we report the
      genetic basis of one type of Sabino spotting pattern in horses that we call
      Sabino 1, with the alleles represented by the symbols SB1 and sb1. Transcripts of
      KIT were characterized by reverse transcriptase polymerase chain reaction (RT
      PCR) and sequencing cDNA from horses with the genotypes SB1/SB1, SB1/sb1, and
      sb1/sb1. Horses with the Sabino 1 trait produced a splice variant of KIT that did
      not possess exon 17. Genomic DNA sequencing of KIT revealed a single nucleotide
      polymorphism (SNP) caused by a base substitution for T with A in intron 16, 1037
      bases following exon 16. The SNP associated with SB1 was designated KI16+1037A.
      This substitution eliminated a MnlI restriction site and allowed the use of PCR
      RFLP to characterize individuals for this base change. Complete linkage was
      observed between this SNP and Sabino 1 in the Tennessee Walking Horse families
      (LOD = 9.02 for Theta = 0). Individual horses from other breeds were also tested.
      All five horses homozygous for this SNP were white, and all 68 horses with one
      copy of this SNP either exhibited the Sabino 1 phenotype or were multipatterned.
      Some multipatterned individuals appeared white due to the additive effect of
      white spotting patterns. However, 13 horses with other Sabino-type patterns did
      not have this SNP. Based on these results we propose the following: (1) this SNP,
      found within intron 16, is responsible for skipping of exon 17 and the SB1
      phenotype, (2) the White and Sabino phenotypes are heterogeneous and this
      mechanism is not the only way to produce the pattern described as "Sabino" or
      "White," and (3) homozygosity for SB1 results in a complete or nearly completely
      white phenotype.

PMID- 16284806
TI  - Effect of temperature on vegetative growth among isolates of Metarhizium
      anisopliae and M. flavoviride.
AB  - Effects of temperature on vegetative growth on a semi-synthetic medium of 22
      isolates of Metarhizium anisopliae and 14 isolates of M. flavoviride were
      determined. The majority of isolates of both species grew between 11 and 32
      degrees C; several isolates grew at 8 and 37 degrees C. None of the isolates grew
      at 40 degrees C. Relative growth rate, calculated from the maximum growth rate
      for each isolate, was significantly affected by temperature and isolate, with
      significant isolate * temperature interactions. The maximum absolute growth rates
      among the isolates ranged from 2.5 mm to 5.9 mm/day. Optimal temperatures were
      generally between 25 and 32 degrees C with several isolates exhibiting optimal
      growth at temperatures as high as 32 degrees C. Overall, relative growth rates
      were greater in isolates of M. anisopliae than M. flavoviride at temperatures of
      25 degrees C or lower; conversely mean relative growth rates were greater in M.
      flavoviride than M. anisopliae at temperatures higher than 25 degrees C. However,
      the two most cold tolerant isolates at 8 degrees C were M. flavoviride and the
      three most heat tolerant at 35 degrees C were M. anisopliae. Since temperature
      growth responses varied considerably between isolates, strain selection according
      to thermal tolerance may be warranted when choosing a strain for development as a
      microbial control agent.

PMID- 16284807
TI  - A quantitative bioassay for extracellular metabolites that antagonize growth of
      filamentous fungi, and its use with biocontrol fungi.
AB  - A bioassay and an empirically derived formula were developed to quantify
      fungitoxic effects. This bioassay can be easily performed and objectively read,
      and it is suitable for low-volume samples originating from aqueous or organic
      solvents. The formula defines the Inhibition Index (I), a single value that
      incorporates both the response to concentrations of the inhibitory compound and
      the persistence of inhibition. Antagonistic efficacy of metabolites produced by
      biocontrol strains of Trichoderma spp. were measured based on inhibition of
      growth of Rhizoctonia solani. Although the bioassay itself was not influenced by
      pH or light conditions, these factors affected metabolite production or activity.
      Aqueous extracts from light-grown germlings of Trichoderma virens inhibited R.
      solani more than extracts from germlings grown in the dark. Low pH increased the
      inhibitory activity of extracts from T. virens. Tests of fungal strains developed
      for biocontrol demonstrated that the bioassay reflected their activity both in
      the field and in other in vitro tests. The bioassay and formula are readily
      adapted for use with other fungi.

PMID- 16284808
TI  - Colletotrichum acutatum is the main cause of Colletotrichum leaf disease of
      rubber in Sri Lanka.
AB  - Colletotrichum gloeosporoides has been described as the causal agent of
      Colletotrichum leaf disease of rubber in Sri Lanka and other parts of the world
      since 1905. A study carried out on vegetative and reproductive characteristics of
      52 isolates from Colletotrichum leaf disease lesions on Hevea brasiliensis in Sri
      Lanka revealed that only 18 isolates belong to Colletotrichum gloeosporioides.
      The remaining 34 isolates represented C. aculatum indicating that C. acutatum is
      the main cause of Colletotrichum leaf disease in Sri Lanka.

PMID- 16284809
TI  - Co-infection by Cryptococcus neoformans and Mycobacterium avium intracellulare in
      AIDS.
AB  - In the observation of various opportunistic pathogens in HIV-positive persons, co
      infection by Cryptococcus neoformans together with Mycobacterium avium
      intracellulare was found if there was a CD4 lymphocyte count as low as 3-20
      microl. In 1540 HIV-positive patients under treatment at a Berlin hospital
      (Auguste-Viktoria-Krankenhaus) during 1985-1994, all AIDS-relevant diseases were
      examined in a multivariate analysis as variables of influence on the
      manifestation of a systemic Mycobacterium avium complex (MAC) infection. The
      analysis involved data on 36 cases of cryptococcosis and 202 cases with a typical
      clinical course in whom MAC had been detected at sterile body sites. As
      significant and independent factors of influence, the following were identified:
      C. neoformans infection, wasting syndrome, lower age, low CD4 lymphocyte count
      and preceding Pneumocystis carinii pneumonia (PcP) prophylaxis. Cryptococcosis
      ranged first with an odds ratio of 2.75. The concomitant manifestation of
      cryptococcosis and systemic MAC infection in six patients is shown. Because both
      opportunists, C. neoformans and avian mycobacteria, may have their common habitat
      in droppings of defined species of pet birds, a common source of infection
      deserves further clinical and epidemiological attention.

PMID- 16284812
TI  - A survey of dermatophytosis in animals in Madras, India.
AB  - Two hundred and eleven dogs (including strictly house and stray dogs) and 170
      cattle in and around the city of Madras, India were screened for the presence of
      dermatophytosis. 106 strains of dermatophytes (89 strains from dogs and 17
      strains from bovines) were isolated. 57/106 strains were Trichophyton
      mentagrophytes var. mentagrophytes and 42/106 strains were of the Microsporum
      gypseum complex. 5 strains of T. rubrum and 2 strains of T. simii were also
      obtained in culture. A predominance of M. gypseum complex isolates was recorded
      in stray dogs and cattle and T. mentagrophytes var. mentagrophytes and T. rubrum
      in strictly house dogs. The family history of the owners of the most of the dogs
      had clear records of dermatophytosis. Further, the owners of the 11 dogs that
      yielded T. mentagrophytes var. mentagrophytes had either tinea corporis or tinea
      pedis. The etiological agent of all the 11 human cases was T. mentagrophytes var.
      interdigitale. Similarly the owners of 4 of the 5 dogs that yielded T. rubrum
      were known T. rubrum patients. All these patients responded to oral griseofulvin
      or ketaconozole, but the recurrence of lesions was noted with the cessation of
      treatment. None of the patients had onychomycosis and the family history of all
      the patients revealed no reports of T. rubrum infections. The pet dogs were
      presumed to be the source of re-infection. Reversed transmission of dermatophytes
      from humans to animals may be the reason for the selective predominance of these
      organisms in strictly house dogs. They also may act as sources of reinfection.
      Most of the animals had small, occult, scattered lesions. These lesions may
      either go unnoticed or are ignored by the owners of the animals. The taxonomic
      status of T. mentagrophytes var. mentagrophytes and T. mentagrophytes var.
      interdigitale was aligned to their teleomorph Arthroderma vanbreuseghemii. Our
      study suggests that the periodic screening and medication of all live-stock are
      essential for the prevention and management of the public health problem caused
      by dermatophytes.

PMID- 16284813
TI  - Examination of some morphologically unusual cultures of Phytophthora species
      using a mitochondrial DNA miniprep technique and a standardised sporangium
      caducity assessment.
AB  - Using the mitochondrial DNA miniprep technique, the identity of sixteen
      morphologically unusual cultures allocated to Phytophthora nicotianae,
      Phytophthora mexicana or Phytophthora porri was determined by comparison with a
      library of mtDNA band patterns obtained from reference cultures. Seven cultures
      were identified as Phytophthora nicotianae (including those assigned to
      Phytophthora mexicana and Phytophthora porri), six as strains of Phytophthora
      palmivora with small, ovoid, weakly caducous sporangia, and one as Phytophthora
      citrophthora. Some cultures of P. nicotianae had a low percentage of caducous
      sporangia. Percentage sporangium caducity, but not sporangium L:B ratio, is
      considered a useful taxonomic criterion for separating species morphologically
      similar to Phytophthora nicotianae. One culture from tobacco in New Zealand had a
      highly unusual morphology and a unique DNA band pattern, but was not
      identifiable. One culture from Acacia mearnsii in South Africa had a unique DNA
      band pattern which was identical to that of an isolate from Annona squamosa from
      Australia previously identified as Phytophthora palmivora, the precise identity
      of which is still unclear. The identity of most isolates from diseased durian was
      found to be Phytophthora palmivora, confirming its role as the main pathogen, but
      P. nicotianae was also identified from this host.

PMID- 16284814
TI  - Formation of alpha- and beta-conidia by Phaeocytostroma ambiguum.
AB  - The formation of conidia in Phaeocytostroma ambiguum on different media and
      conditions was investigated in this study. Carnation leaf agar (CLA) and a 12 h
      photoperiod (24/18 degrees C) provided excellent conditions for the promotion of
      rapid formation of both alpha (alpha) and beta (beta) conidia in a number of P.
      ambiguum isolates. The dimensions of alpha- and beta-conidia amounted to 6.0-19.6
      x 3.8-7.5 microm and 6.0-24.9 x 1.1-2.6 microm, respectively. They were produced
      on short or elongate, simple and branched conidiophores. beta-conidia have not
      been described before in P. ambiguum. Intermediate conidia were rarely found.

PMID- 16284817
TI  - Identity of Fusarium nygamai isolates with long and short microconidial chains
      from millet, sorghum and soil in Africa.
AB  - Several Fusarium species have been found associated with millet and sorghum in
      Nigeria, Lesotho and Zimbabwe. Amongst these, some isolates were originally
      identified as short- and long-chained types of F. nygamai. However, there was
      some question as to the correct identification of the long chained types. This
      study reclassified some of the isolates with long microconidial chains as F.
      moniliforme. Morphologically, these strains do not produce chlamydospores like F.
      nygamai, but produce swollen hyphal cells or resistant hyphae. The isolates in
      this study were crossed with the mating-type tester strains of Gibberella
      fujikuroi (F. moniliforme and G. nygamai (F. nygamai). Of the isolates with long
      chains of microconidia and other characteristics of F. moniliforme, 36% crossed
      with mating population "A" of G. fujikuroi. Of the isolates with characteristics
      of F. nygamai, 65% crossed with the testers used to produce the teleomorph of F.
      nygamai. Mating tests support the separation of the sample population into F.
      moniliforme and F. nygamai. The results of this study show that genetics can be
      an aid in resolving some problems in fungal taxonomy.

PMID- 16284824
TI  - Extracellular enzymatic activity of Fusarium section Liseola isolates.
AB  - Extracellular enzymatic activity of Fusarium species from section Liseola was
      determined by the Api-Zym test, a semiquantitative method for assaying different
      cellular enzymes. This enzyme testing system was evaluated for possible use as a
      species identification aid. Twenty-two strains of Fusarium section Liseola were
      used: 8 of F. moniliforme, 6 of F. proliferatum, 6 of F. subglutinans and 2 of F.
      anthophilum. The optimal spore concentration was also determined for maximal
      activity in Api-Zym assay. According to our findings, the species showed little
      difference in Api-Zym enzymatic profiles, being not suitable for identification
      of these species. Only F. subglutinans and F. anthophilum showed a different
      enzymatic pattern.

PMID- 16284830
TI  - Influence of commercially derived lipids and a surfactant on the mode of
      germination and process of germ-tube formation in primary conidia of two species
      of Erynia subgenus Neopandora (Zygomycotina: Entomophthorales.
AB  - Primary conidia of the entomopathogens Erynia (subgenus Neopandora) delphacis (1
      isolate) and Erynia (Neopandora) neoaphidis (3 isolates) were stimulated to form
      germ-tubes with Tween 20 and with free, long-chain fatty acids, each incorporated
      into Entomophthora complete medium (ECM). When combined with other basal media
      (three tested), these compounds did not stimulate germ-tube formation.
      Triacylglycerols and vegetable oils, added to the same media, allowed almost
      complete resporulation in the fungi. In both species, Tween 20 (0.1%) encouraged
      greater germ-tube production (41-69%) than the fatty acids (0.1%) (< or = 36%).
      For E. delphacis, Tween 20 and the fatty acids differed significantly, but for E.
      neoaphidis the differences were almost always insignificant. Myristic and oleic
      acids stimulated germ-tube formation in both species. Palmitic acid allowed
      almost complete resporulation of the fungi, except for one isolate of E.
      neoaphidis that formed germ-tubes. Linoleic acid, tested only for E. delphacis,
      was fungistatic to most conidia. Higher concentrations of the fatty acids (< or =
      1%) did not increase germ-tube formation, except 1% oleic acid which affected E.
      delphacis alone (>80% germination and germ-tubes). Linoleic acid, and sometimes
      also myristic and oleic, were fungistatic and/or toxic, depending on their
      concentration and on medium composition. Addition of fatty acids to ECM usually
      extended the lag period, and altered the morphology of the conidia and germ
      tubes. These phenomena were not observed with Tween 20. Colonies were formed by
      E. delphacis alone, stimulated by ECM supplemented with Tween 20 or fatty acids.
      The results are discussed with respect to biological and physiological aspects of
      germination, and with respect to the mode of action of the fatty acids and the
      surfactant.

PMID- 16284837
TI  - First record of Cercospora pistiae causing leaf spot of water lettuce (Pistia
      stratioites) in Brazil, with particular reference to weed biocontrol.
AB  - Pistia stratioites, the water lettuce, is an important pantropical aquatic weed.
      It has been the target of successful classical biocontrol programmes utilizing an
      insect natural enemy collected in Brazil and introduced into Australia, Papua New
      Guinea and South Africa. Little attention was given to the fungal pathogens
      associated with this weed as potential biocontrol agents. An 11-month field
      survey in the state of Rio de Janeiro involving repeated visits to 12 sites, and
      a 2-month survey in the Amazonas Basin (Amazonas state) in Brazil, yielded only
      one pathogenic fungus on P. stratioites. This was identified as Cercospora
      pistiae. No previous record of this species has been made in Brazil nor in the
      New World. The fungus is described and its taxonomy and biocontrol potential
      discussed herein. C. pistiae is a damaging pathogen of water lettuce. Its
      distribution was restricted to two interconnected sites in Rio de Janeiro. A
      literature and herbaria survey yielded few fungi associated to water lettuce (8
      species), probably reflecting a lack of adequate collection in the centre of
      origin of the plant.

PMID- 16284838
TI  - Fungicidal and binding properties of three plant peptides.
AB  - The fungicidal properties of plant seed peptides from Heuchera sanginea (Hs
      AFP1), Raphanus sativus (EA-AFP2), and Impatiens balsamina (Ib-AMP3) were
      determined for the non-germinated and germinated conidia of Aspergillus flavus
      and Fusarium moniliforme. These peptides were weakly lethal for germinated but
      not for non-germinated conidia of A. flavus. Both non-germinated and germinated
      conidia of F. moniliforme were susceptible to these peptides. Overall, F.
      moniliforme was more susceptible than A. flavus to the peptides. The peptides
      bound strongly to chitin, mannan, galactocerebrosides, and sphingomyelin. Binding
      results varied for ergosterol, cholesterol, and beta1,3-glucan.

PMID- 16284839
TI  - Contribution to the study of the chemical composition of Verticillium albo-atrum
      secretions in liquid media.
AB  - Verticillium albo-atrum culture filtrates contain numerous metabolites such as
      enzymes and toxins. Their purification was carried out by high phase liquid
      chromatography (HPLC). In this study, we set out to look for other lighter
      metabolites that could be identified by gas chromatography coupled to mass
      spectrometry (GC-MS). The analyses revealed the presence of many volatile
      chemical compounds, some of which are of great economic interest such as methyl
      paraben, propyl paraben tethane and xylene. Verticillium albo-atrum, which is a
      pathogen of many market-garden and fodder crops, is able to produce substances
      that can be used in both the agro-food and cosmetic industries.

PMID- 16284844
TI  - Ergosterol accumulation and oil quality changes in stored soybean invaded by
      Aspergillus ruber (A. glaucus group).
AB  - Soybean seed samples inoculated with spores of Aspergillus ruber were stored for
      20 to 140 days at 25 +/- 1 degrees C with moisture content varying from 11.3% to
      17.7%. Seeds were colonised by the fungus within 20 days at all moisture levels.
      Ergosterol concentration in seeds increased with time of storage, being slow in
      samples with moisture content of 11.3% to 13.1% and more rapidly in those with
      higher moisture content. Free fatty acid (FFA) content also increased following
      the pattern of ergosterol. Equations were used to predict minimum safe storage
      period of the seeds at 25 degrees C. The rise in FFA is due to increase of A.
      ruber mass within the seed. Fungal growth did not affect fatty acids profiles or
      iodine index of the extracted oil. The results suggest revision of the present
      recommendations regarding seed moisture during storage. The FFA concentration of
      a seed lot can be used as a sensitive indicator of seed deterioration due to
      storage fungi.

PMID- 16284845
TI  - Growth at different temperatures and on fungicide amended media: two
      characteristics to distinguish Colletotrichum species pathogenic to rubber.
AB  - Slower growth at temperatures ranging from 15 to 32.5 degrees C and high
      tolerance of three fungicides, benomyl, carbendazim and thio-phanate methyl, were
      shown to be reliable characteristics in distinguishing rubber isolates of
      Colletotrichum acutatum from Colletotrichum gloeosporioides in addition to the
      characteristics reported previously.

PMID- 16284846
TI  - A survey on the occurrence of mycotoxins in wheat and maize from western Romania.
AB  - Samples of wheat (n = 25) and maize (n = 30) for animal consumption, collected in
      1997 after harvest from western Romania, were analyzed by enzyme immunoassays for
      mycotoxin contamination. Toxins analyses included deoxynivalenol (DON), 3
      acetylDON, 15- acetylDON, fusarenone X (FX), T-2 Toxin (T-2), diacetoxyscirpenol
      (DAS), zearalenone (ZEA), fumonisin B(1) (FB(1)), aflatoxin B(1) (AFB(1)),
      ochratoxin A (OA), and citrinin (CT). DON and acetylDONs were the major
      contaminants in wheat (100%) and maize (46%). Median values for DON, 3-acetylDON,
      and 15-acetylDON were 880 microg kg(-1), 66 microg kg(-1), and 150 microg kg(-1)
      in wheat, and 890 microg kg(-1), 180 microg kg(-1), and 620 microg kg(-1) in
      maize, respectively. Additionally, 3,15-diacetylDON was detected in some samples
      by HPLC-EIA analysis. All samples were negative for FX (<150 microg kg(-1)). T-2
      was found in wheat (n = 6) and maize (n = 1) at levels between 13 and 63 microg
      kg(-1). DAS (2.6 microg kg(-1)) was found in one maize sample. ZEA occurred in
      all wheat and in four maize samples, median values were 10 microg kg(-1) and 250
      microg kg(-1), respectively. One maize sample contained FB(1) (140 microg kg(
      1)). All samples were AFB(1)-negative (<4 microg kg(-1)). OA was found in one
      wheat sample (37 microg kg(-1)), CT was found in one maize sample (580 microg kg(
      1)). This first reported natural occurrence of a range of mycotoxins in Romanian
      feeding stuff shows that DON and acetyl DONs may be present at levels which may
      affect animal production.

PMID- 16284849
TI  - Some coprophilous fungi from Kenya.
AB  - The occurrence of coprophilous fungi on samples of antelope, buffalo, zebra and
      hippopotamus dung collected from the Marula Estates in Kenya was recorded. A
      hundred and seventy three fungal isolates representative of 40 genera and 59
      species were identified. Among these species, 23 were Ascomycetes (39%), 30
      Deuteromycetes (50.8%), 5 Zygomycetes (8.5%) and 1 Basidiomycete (1.7%).
      Ascobolus immersus, Coprotus niveus, Iodophanus carneus, Lasiobolus
      lasioboloides, Podospora anserina, P. australis and Sporormiella minima were the
      dominant species occurring in the dung of these animals. Notes on infrequent or
      interesting Ascomycetes include Kernia nitida, Saccobolus versicolor, Sordaria
      fimicola and others. The interdependence of the vegetation of this area with the
      fungi occurring on the dung of these animals is discussed.

PMID- 16284850
TI  - Identification of Pythium carolinianum causing 'root rot' of cotton in Egypt and
      its possible biological control by Pseudomonas fluorescens.
AB  - A severe root rot disease of cotton caused by Pythium carolinianum was diagnosed
      in a cotton field in Beni-Musa village, 20 km southwest of El-Minia city, Egypt,
      during the summer of 1996. This was the first reported isolation of this fungus
      in Egypt. In the light of the importance of the cotton industry in Egypt,
      research was initiated to develop a biocontrol agent against Pythium
      carolinianum. In vitro agar plate technique identified a Pseudomonas fluorescens
      strain that was highly antagonist to Pythium carolinianum. Subsequent plant
      growth experiments establish that substantial disease control could be obtained
      by applying Pseudomonas fluorescens to the soil. Optimal control was obtained by
      mixing the bacteria with the soil rather than by dipping the cotton roots in the
      bacterial suspension immediately before planting. Disease was more severe in
      autoclaved soil than in nonsterile soil.

PMID- 16284851
TI  - Biological control of Sclerotinia sclerotiorum attacking soybean plants.
      Degradation of the cell walls of this pathogen by Trichoderma harzianum (BAFC
      742). Biological control of Sclerotinia sclerotiorum by Trichoderma harzianum.
AB  - Two experiments of biological control of Sclerotinia sclerotiorum, one in the
      greenhouse and the other in the field, were carried out with soybean and
      Trichoderma harzianum as host and antagonist, respectively. Significant control
      of disease was achieved in both experiments, but there were no significant
      differences in plant growths. In the greenhouse, the application of T. harzianum
      as alginate capsules, increased the survival of soybean plants more than 100%
      with respect to the disease treatment. In the field, T. harzianum treated plants
      survived 40% more than those from the disease treatment, showing a similar
      survival level to control plants. Besides, a significant reduction (62.5%) in the
      number of germinated sclerotia was observed in the Trichoderma treated plot.
      Chitinase and 1,3-beta- glucanase activities were detected when T. harzianum was
      grown in a medium containing Sclerotinia sclerotiorum cell walls as sole carbon
      source. In addition, electrophoretic profiles of proteins induced in T. harzianum
      showed quantitative differences between major bands obtained in the media induced
      by S. sclerotiorum cell walls and that containing glucose as a sole carbon
      source.

PMID- 16284852
TI  - Evaluation of ash from some tropical plants of Nigeria for the control of
      Sclerotium rolfsii Sacc. on wheat (Triticum aestivum L.).
AB  - Eleven ash samples, from organs of nine tropical plants, were screened for their
      abilities to inhibit mycelial growth and sclerotial germination of a Nigerian
      isolate of Sclerotium rolfsii on agar and in the soil. Ten ash samples showed
      some activity against mycelial growth of S. rolfsii in vitro. Ash samples from
      Delonix regia stem wood, Mangifera indica leaf and Vernonia amygdalina leaf were
      most effective as each totally inhibited mycelial growth of S. rolfsii in vitro.
      Ocimum gratissimum leaf ash, D. regia wood ash and Musa paradisiaca flower bract
      ash inhibited sclerotial germination on agar. Nine ash samples protected seeds
      against pre-emergence rot. Ash from M. indica leaf, V. amygdalina leaf and
      Azadirachta indica leaf protected seedlings against post-emergence infection.
      Eichornia crassipes ash, which was ineffective in vitro, offered some protection
      to seeds in soil against pre-emergence rot. The study demonstrates potentials of
      ash samples from tropical plants in control of S. rolfsii on wheat.

PMID- 16284853
TI  - Identification of Armillaria field isolates using isozymes and mycelial growth
      characteristics.
AB  - This research was conducted to develop procedures based on mycelial growth
      characteristics and patterns of esterase (EST) and polyphenol oxidase (PPO)
      production by diffuse mycelia for identification of Armillaria field isolates
      from Quercus-Carya-Pinus forests in the Ozark Mountains (central USA). The 285
      isolates collected were first identified by standard diploid-haploid pairing
      tests as A. gallica, A. mellea, or A. tabescens. A strong PPO band was diagnostic
      for A. gallica. All A. mellea isolates tested and 91% of the A. tabescens
      isolates tested were distinguished based on production of EST bands in three
      standardized R f ranges. A procedure based on mycelial growth and morphology on
      tannic acid medium (TA) at 24 degrees C and on malt extract medium (ME) at 33
      degrees C correctly identified 98% of A. gallica isolates and all A. mellea and
      A. tabescens isolates. On TA, A. gallica grew slowest. On ME, A. mellea grew
      slowest: mycelial morphology differed among species; A. gallica typically stained
      the agar and produced an appressed/submerged growth pattern with concentric bands
      of decreasing hyphal density, A. mellea typically did not stain the agar and
      produced round mycelia with smooth margins and abundant aerial hyphae, A.
      tabescens typically stained the agar and grew appressed/submerged with very
      irregular margins and patchy hyphal density. These are the first published
      systems evaluating the potential for identifying Armillaria field isolates based
      on their mycelial growth characteristics and EST and PPO complements.

PMID- 16284855
TI  - The effect of selected allelochemicals on germination of conidia and blastospores
      and mycelial growth of the entomopathogenic fungus, Paecilomyces fumosoroseus
      (Deuteromycotina: Hyphomycetes).
AB  - Selected allelochemicals that protect plants from invasion by plant pathogenic
      fungi were investigated for their activity against the entomopathogenic fungus,
      Paecilomyces fumosoroseus. The alkaloids tomatine, solanine, and camptothecin;
      the furanocoumarin, xanthotoxin; and the phenolic, tannic acid were tested for
      their effects on germination of conidia and blastospores and growth of mycelia.
      The LC50 values (corresponding to 50% inhibition of germination) for tomatine,
      solanine, camptothecin, xanthotoxin and tannic acid were 51.6, 95.9, 55.9, 83.0
      and 72.8 mg/l respectively. When blastospores were placed on media containing a
      concentration of the individual allelochemicals that inhibit germination in
      approximately 50% of conidia, all but blastospores on tomatine had significantly
      less germination than did aerial conidia. Growth rates of mycelia were slowest in
      the camptothecin medium, followed by those of tomatine and xanthotoxin and were
      not significantly different from controls in the media containing solanine and
      tannic acid. A multitude of biotic and abiotic factors are responsible for
      specificity and degree of pathogenicity of entomopathogens. The effect of crop
      plant chemistry on the efficacy of entomopathogens should be quantified further
      in order to maximize their potential when used concomitantly with resistant plant
      varieties.

PMID- 16284856
TI  - Investigation of the radiation effects on Brown Rot disease of Golden Delicious
      apples, inoculated with the fungus Monilinia fructigena.
AB  - The effects of 0, 1.5 and 3 KGy gamma-irradiation on Brown Rot disease affecting
      Golden Delicious apples are investigated. The apples were artificially inoculated
      with Monilinia fructigena fungus before and after irradiation. Results show
      clearly that radiation induces a delay in fungus development, even when it is not
      directly affected. The effect of radiation on the apples' substrate seems to be
      considerable, being the main factor affecting fungal growth. Radiation doses of
      1.5 and 3 KGy do not seem to produce strong differences in the fungal growth.
      Irradiation, however, is very effective, producing important changes of practical
      interest for apples infected before or after irradiation.

PMID- 16284857
TI  - Aflatoxin B1, zearalenone and deoxynivalenol production by Aspergillus
      parasiticus and Fusarium graminearum in interactive cultures on irradiated corn
      kernels.
AB  - The influence of inoculum size in the production of aflatoxin B1 (AFB1),
      zearalenone (ZEN) and deoxynivalenol (DON) was determined when Aspergillus
      parasiticus NRRL 3000 and Fusarium graminearum ITEM 124 were cultured alone and
      in pairs on irradiated corn kernels at 28 degrees C and 0.97 water activity
      (a(w)). The highest levels of AFB1 produced by A. parasiticus were produced at
      the lowest levels of the inoculum (10(3) spores/ml). No significant differences
      were observed in ZEN and DON production at any inoculum level during the
      experimental period. When A. parasiticus was co-inoculated with F. graminearum
      both to the same inocula (10(6) spores/ml), AFB(1) inhibition percentage were 60,
      72 and 56% at 10, 20 and 35 days of incubation respectively, while at 10(6)
      spores/ml the percentages of inhibition were 34, 84 and 93% at 10, 20 and 35
      days. In the mixture cultures A. parasiticus 10(3) x F. graminearum 10(6)
      spores/ml the percentage of inhibition of AFB(1) oscillated in 99% during all the
      incubation. In the interaction A. parasiticus 10(6) spores/ml x F. graminearum
      10(3) spores/ml the accumulation of AFB1 decreased in 80, 94 and 86% at 10, 20
      and 35 days of incubation respectively. In single culture F. graminearum was
      inoculated with 10(3) or 106 spores/ml and the highest levels of ZEN and DON were
      detected at 35 days of incubation. The levels oscillated in 538-622 microg/kg for
      ZEN and 870-834 mug/kg for DON respectively. In paired cultures there were no
      significant differences in the levels regardless of the spore concentrations
      during the incubation time.

PMID- 16284858
TI  - Does the mycotoxin citrinin function as a sun protectant in conidia from
      Penicillium verrucosum.
AB  - Our results demonstrate high concentrations of the UV absorbing mycotoxin
      citrinin in the outer layer of spores from three citrinin-producing strains of
      Penicillium verrucosum, which is released in an aqueous environment. An important
      function of the toxin could be to act as a sun protectant in order to create
      favorable conditions during the initial germination process. When spores from
      these strains of P. verrucosum were examined by confocal microscopy, a clearly
      visible fluorescent layer associated with the cell wall was observed. The strains
      were grown on agar plates, and the mycelial mat was washed with saline. This
      suspension contained at least 95% of the spores and particulate material, which
      was removed by filtration after counting the conidia. An aliquot of this filtrate
      was extracted and citrinin was purified by high pressure liquid chromatography.
      The absorbance at 319 nm was used to calculate the amount of UV absorbing
      material released from the spores. Based on the spore numbers in the suspension
      of the saline extract, we estimated that this material released was 1.4-4.1 pg
      per spore or 8-24% of the spore weight. Citrinin (and minor amounts of ochratoxin
      A and some other unidentificable fluorescent compounds) were observed in the
      filtrate when subjected to thin layer chromatography.

PMID- 16284860
TI  - A preliminary study of the occurrence of actidione-resistant fungi in sediments
      of Catalonian river mouths (Spain). I. Keratinolytic fungi and related
      Onygenales.
AB  - Sediments from eight river mouths along the Catalonian coast (Spain) were
      surveyed for keratinolytic fungi and related Onygenales. The actidione plating
      technique was employed. Of 532 actidione-treated sediment samples, 268 (50.3%)
      were positive for the fungi. Altogether, 384 fungal strains from 35 species were
      isolated from the samples. Narasimhella marginospora, Aphanoascus fulvescens,
      Neoarachnotheca keratinophila with its anamorph Myriodontium keratinophilum,
      Narasimhella hyalinospora, Beauveria alba, Sporothrix schenckii, Chrysosporium
      lobatum and Gymnoascus littoralis were the predominant species in sediments.
      Abundance of N. marginospora was clearly correlated with the degree of water
      pollution with sewage.

PMID- 16284861
TI  - Induction of fungal disease resistance in Vicia faba by dual inoculation with
      Rhizobium leguminosarum and vesicular-arbuscular mycorrhizal fungi.
AB  - Infection of Vicia faba with Bothytis fabae causes significant decreases in
      growth vigour, total nitrogen content, number of nodules and nutrient
      accumulation. Na-uptake and phenolics concentration increased compared to that of
      noninfected plants. In contrast, dual inoculation of Rhizobium and VA mycorrhizae
      increased all above parameters suggesting a distinct improvement of the plants.
      The results also revealed that an inverse correlation may exist between phenolic,
      calcium, magnesium and zinc concentrations in mycorrhizal plant tissues grown in
      presence of rhizobial bacteria and the disease severity. From these findings we
      conclude a possible role of both VA mycorrhizal fungi and rhizobial bacteria in
      the decrease of susceptibility of plants.

PMID- 16284862
TI  - Fungal pathogens of Euphorbia heterophylla and E. hirta in Brazil and their
      potential as weed biocontrol agents.
AB  - A two-year survey of the fungi associated with two important congeneric
      pantropical weeds, Euphorbia heterophylla and E. hirta, was conducted in part of
      their native range in southern Brazil. Sampling was concentrated mainly in Rio de
      Janeiro State and ten species were identified as pathogens of these weeds. Two
      taxa, Botrytis ricini and Uromyces euphorbiae, were common to both weed hosts.
      Alternaria euphorbiicola, Bipolaris euphorbiae, Melampsora sp., Oidium sp. and
      Sphaceloma poinsettiae were recorded only from E. heterophylla, whereas
      Colletotrichum gloeosporioides, Sphaceloma sp. and Sphaerotheca fuliginea were
      restricted to E. hirta. Botrytis ricini and Colletotrichum gloeosporioides are
      new records for E. hirta, and Alternaria euphorbiicola and Sphaerotheca fuliginea
      are new host records for Brazil. Bipolaris euphorbiae, previously identified as
      Helminthosporium sp., is considered to be the correct name for the causal agent
      of a major disease of E. heterophyllum in Brazil. The potential of these
      pathogens as biocontrol agents is discussed and the mycobiota associated with
      both these weeds worldwide is reviewed.

PMID- 16284864
TI  - Keratinophilic fungi isolated from soils of Mumbai, India.
AB  - Eighty-seven soil samples were collected from various areas of Mumbai and its
      vicinity to determine the prevalence of keratinophilic fungi. From the 55
      positive samples (63.21%), a total of four genera with nine species were isolated
      viz. Chrysosporium indicum (28.73%),C. lobatum (2.29 %), C. sp.I (1.14%), C. sp.
      II (1.14%),C. tropicum (1.14%),C. zonatum (2.29%),Ctenomyces serratus
      (2.29%)Malbranchea aurantiaca (2.29%) andMicrosporum gypseum complex (21.83%).

PMID- 16284865
TI  - Fungal deterioration of melon seeds stored in jute sacks and polyethylene bags in
      Ago-Iwoye, southwestern Nigeria.
AB  - Laboratory studies were carried out in the Department of Biological Sciences,
      Ogun State University, Ago-Iwoye, southwestern Nigeria, to determine the extent
      of fungal deterioration of melon seeds stored in two types of storage bags viz;
      jute and polyethylene bags. Melon seeds of varieties Tc139 and V2 were stored in
      jute and polyethylene bags under ambient conditions using the 2 x 2 factorial
      design (variety vs type of bag) for 12 months. The moisture content (mc),
      incidence of visible mouldiness (ivm) and germinability of the stored seeds were
      determined monthly. The mc of Tc139 ranged from 6.1 to 6.7% in jute and 6.2 to
      6.5% in polyethylene bags. The ivm which was initially 2.1% increased to 10.7%
      and 5.5% in jute and polyethylene bags respectively, after 12 months in storage.
      The germination percentage decreased from 96.3% to 28.7% and 45.3% in jute and
      polyethylene bags, respectively. The mc of V2 stored in jute and polyethylene
      bags varied from 5.9 to 6.4%, and 5.8 to 6.2%, respectively. The ivm increased
      from 1.8% before storage to 8.9% and 4.8% in jute and polyethylene bags,
      respectively, after 12 months. The percentage seed germination declined from
      98.0% to 37.3% in jute and 48.7% in polyethylene bags after 12 months. Decreased
      incidence of field fungi namely: Alternaria,Botryodiplodia theobromae,
      Cladosporium, Fusarium and Macrophomina phaseolina was accompanied by
      simultaneous increase in storage fungi viz: Aspergillus, Penicillium, and
      Rhizopus with prolonged storage.

PMID- 16284866
TI  - Effect on trend estimates of the difference between survey respondents and non
      respondents: results from 27 populations in the WHO MONICA Project.
AB  - INTRODUCTION: In the World Health Organization (WHO) MONICA (multinational
      MONItoring of trends and determinants in CArdiovascular disease) Project
      considerable effort was made to obtain basic data on non-respondents to community
      based surveys of cardiovascular risk factors. The first purpose of this paper is
      to examine differences in socio-economic and health profiles among respondents
      and non-respondents. The second purpose is to investigate the effect of non
      response on estimates of trends. METHODS: Socio-economic and health profile
      between respondents and non-respondents in the WHO MONICA Project final survey
      were compared. The potential effect of non-response on the trend estimates
      between the initial survey and final survey approximately ten years later was
      investigated using both MONICA data and hypothetical data. RESULTS: In most of
      the populations, non-respondents were more likely to be single, less well
      educated, and had poorer lifestyles and health profiles than respondents. As an
      example of the consequences, temporal trends in prevalence of daily smokers are
      shown to be overestimated in most populations if they were based only on data
      from respondents. CONCLUSIONS: The socio-economic and health profiles of
      respondents and non-respondents differed fairly consistently across 27
      populations. Hence, the estimators of population trends based on respondent data
      are likely to be biased. Declining response rates therefore pose a threat to the
      accuracy of estimates of risk factor trends in many countries.

PMID- 16284867
TI  - Childhood leukaemia incidence in Hungary, 1973-2002. Interpolation model for
      analysing the possible effects of the Chernobyl accident.
AB  - The incidence of childhood leukaemia in Hungary has yet to be reported, although
      data are available since the early 70s. The Hungarian data therefore cover the
      time before and after the Chernobyl nuclear accident (1986). The aim of this
      study was to assess the effects of the Chernobyl accident on childhood leukaemia
      incidence in Hungary. A population-based study was carried out using data of the
      National Paediatric Cancer Registry of Hungary from 1973 to 2002. The total
      number of cases was 2204. To test the effect of the Chernobyl accident the
      authors applied a new approach called 'Hypothesized Impact Period Interpolation'
      model, which takes into account the increasing trend of childhood leukaemia
      incidence and the hypothesized exposure and latency times. The incidence of
      leukaemia in the age group 0-14 varied between 33.2 and 39.4 per million person
      years along the observed 30 year period, and the incidence of childhood leukaemia
      showed a moderate increase of 0.71% annually (p = 0.0105). In the period of the
      hypothesized impact of the Chernobyl accident the incidence rate was elevated by
      2.5% (95% CI: -8.1%; +14.3%), but this change was not statistically significant
      (p = 0.663). The age standardised incidence, the age distribution, the gender
      ratio, and the magnitude of increasing trend of childhood leukaemia incidence in
      Hungary were similar to other European countries. Applying the presented
      interpolation method the authors did not find a statistically significant
      increase in the leukaemia incidence in the period of the hypothesized impact of
      the Chernobyl accident.

PMID- 16284868
TI  - Heterogeneity of prognostic profiles in non-small cell lung cancer: too many
      variables but a few relevant.
AB  - OBJECTIVE: Many prognostic factors, exceeding 150, for non-small cell lung cancer
      (NSCLC) are mentioned in the literature. The different statistical weight of the
      some variables at issue, their heterogeneity and their clinical uselessness is
      reviewed. STUDY DESIGN AND SETTING: Survival analysis of a cohort of NSCLC
      operated (n = 1730, 1993-1997) was carried out utilizing different statistical
      approaches: Cox proportional hazard analysis (CPHA), logistic regression (LRA),
      and recursive partitioning (CART). RESULTS: CPHA identified 13 prognostic
      variables and 11 LRA. Of the 17 possible variables, 10 are coincident. CART
      provided five different diagnostic groups but only three differentiated survival
      levels. Parsimonious models were constructed including only T and N cancer
      staging variables. Areas under the ROC curve of 0.68 and 0.68 were found for CPHA
      and LGA parsimonious models respectively, and 0.72 and 0.71 for complete models.
      CONCLUSION: Variables with a minimal impact on the respective models and thus
      with little or scarce predictive clinical repercussion were identified.
      Differences in the prognostic profile of survival can be caused by the different
      methodological approaches used. No relevant differences were found between the
      parsimonious and complete models. Although the amount of information managed is
      considerable, there continues to be a large predictive gap yet to be explained.

PMID- 16284870
TI  - Epidemiological survey of Tourette syndrome in children and adolescents in
      Wenzhou of P.R. China.
AB  - An epidemiological survey on Tourette syndrome (TS) in a developing country is
      relatively scarce. This study was conducted to investigate the prevalence and
      distribution of TS in children and juveniles aged 7-16 years in Wenzhou of P.R.
      China. A total of 9742 children and adolescents were included in this survey.
      Cross-sectional study with stratified-cluster sampling method was used. The
      prevalence of TS among school-age children was estimated to be an average of
      0.43%. The ratio of male to female was 10.6 to 1 (0.74% for males and 0.07% for
      females). Pupils in the age range of 7-16 years are more likely to have comorbid
      disorders. The mean age at onset of TS was 7.7+/-2.7 years, with 45.2% of them at
      the age of 6-7. The rate of delayed diagnosis, misdiagnosis and misclassification
      of the syndrome were 78.6, 42.9 and 23.8%, respectively. This survey supports
      that TS is a common disease prevalent amongst children and juveniles in Wenzhou
      area of P.R. China, and its incidence was correlated with age and sex and often
      misdiagnosed and misclassified.

PMID- 16284869
TI  - Lifecourse determinants of fasting and post-challenge glucose at age 50 years:
      the Newcastle Thousand Families Study.
AB  - Suboptimal nutrition in early life is suggested to influence plasma glucose
      levels in later life. This study aimed to determine and quantify influences on
      plasma glucose levels at age 50. We studied 169 men and 219 women from the
      Newcastle Thousand Families cohort who attended for clinical examination,
      including measurements of fasting and 2 h post oral glucose load) at age 50. A
      lifecourse approach was used to estimate proportions of variance in plasma
      glucose levels accounted for by each stage of the lifecourse. Birth weight
      significantly predicted two-hour glucose levels in men (adjusted p = 0.03). Body
      composition was a significant predictor of both glucose measures in both genders.
      Interactions existed between body composition and birth weight on fasting glucose
      in men and two-hour glucose in women and between gender and birth weight on both
      outcome measures. Fetal life factors directly explained little variation in
      either glucose measure (< 2%). Adult lifestyle and body composition directly
      explained larger proportions of the variances (8-13%) for fasting and two-hour
      glucose than early life measures. The significant effect of birth weight on two
      hour glucose seen in men provides support for the fetal origins hypothesis,
      although adult factors may be more important. Any effect of birth weight on later
      plasma glucose levels may be compounded by additional effects of adult body
      composition.

PMID- 16284871
TI  - Seasonal variations in mood and behaviour associated with gender, annual income
      and education: the Hordaland Health Study.
AB  - OBJECTIVE: To explore the relationship between demographic factors and seasonal
      changes in mood and behaviour. METHOD: A health survey was conducted among 40-45
      year old inhabitants in Hordaland County, Norway. The Global Seasonality Score,
      investigating seasonal symptoms, was given to 4299 men and 9983 women. Response
      rates among those receiving the questionnaire were 79.8% for men (n = 3432) and
      81.2% for women (n = 8223). RESULTS: High seasonality was reported by 18.4% of
      men and 22.2% of women. Female gender, low educational level, high level of
      affective symptomatology and low household income correlated with high
      seasonality. Among men, being single was also a determinant factor for high
      seasonality. Reported seasonality also depended on which month the questionnaire
      was filled in. CONCLUSIONS: In this study, high seasonality was most prevalent
      among females, being single, having a low annual income and a low education
      level. The latter two findings are different from expectations which could be
      drawn from previous studies suggesting an opposite association.

PMID- 16284872
TI  - A population-based case-control study of isolated anophthalmia and
      microphthalmia.
AB  - The purpose of the study was to reveal the etiological factors in the origin of
      isolated an/microphthalmia. The dataset of the Hungarian Case-Control
      Surveillance of Congenital Abnormalities, 1980-2002 containing 56 cases with
      isolated an/microphthalmia and 22,744 malformed controls with other non-ocular
      defects from the Hungarian Congenital Abnormality Registry, in addition of 56
      matched control pairs and 37,837 population controls without defects from the
      National Birth Registry, was evaluated. Exposure data and family history were
      collected (i) prospectively by prenatal logbook and other medical records, (ii)
      retrospectively through a structured questionnaire filled-in by mothers, and
      (iii) information obtained by regional nurses at home visit of non-respondent
      mothers. The autosomal recessive origin of isolated an/microphthalmia was
      indicated in about 10% of cases on the basis of sib recurrence. Cases with
      isolated an/microphthalmia had a much shorter mean gestational age and smaller
      mean birth weight, a much larger proportion of preterm birth and low birthweight.
      Their mothers were younger with a predominance of first birth order, frequently
      unmarried with low socioeconomic status. These findings are in agreement with a
      much higher prevalence at birth of cases with isolated an/microphthalmia in the
      gypsy population probably due to the interaction of inbreeding effect and low
      socioeconomic status. Further molecular genetic studies are needed to identify
      gene mutations of isolated an/microphthalmia in the Hungarian gypsy population.

PMID- 16284873
TI  - Effect of gender, age, and severity of asthma attack on patterns of emergency
      department visits due to asthma by month and day of the week.
AB  - OBJECTIVE: To examine the pattern and strength of seasonal fluctuations in
      emergency department (ED) visits due to asthma, by month and day of the week, by
      the patient's age, gender, and severity of asthma attack. METHODS: Time series
      analysis of ED visits was conducted among patients with asthma aged from 18 to 55
      years who visited Ontario EDs between April 1, 2001 and March 31, 2004.
      Autoregressive regression models with months and days of the week as predictors
      were fitted for (1) all patients; (2) females and males separately; (3) each
      combination of gender and age group, and (4) each combination of gender and level
      of severity. The strength of seasonality in each group of patients was estimated
      from the R2-statistic derived from autoregression models. RESULTS: For all
      patient groups, the highest number of ED visits occurred in October and December,
      and on Sundays and Mondays. Month of January and Fridays were associated with a
      decreased number of visits. The strength of seasonality was similar in men and
      women (R2 = 0.52), was the highest in young patients and decreased with age, in
      men more rapidly than in women. Severe cases of asthma attacks exhibited weaker
      seasonality (R2 = 0.30) compared to mild (R2 = 0.45) or moderate (R2 = 0.53)
      cases. CONCLUSION: The strength of seasonal patterns of asthma ED visits is
      influenced by age and the severity of attack, and to a lesser extent, gender.
      Understanding the significance of seasonal precipitants of asthma in different
      patients subgroups could lead to better management strategies.

PMID- 16284874
TI  - A pedagogical farm as a source of Q fever in a French city.
AB  - Q fever is a worldwide zoonosis caused by Coxiella burnetii and presents as both
      acute or chronic cases. The disease can be transmitted from animal reservoirs to
      humans by inhalation of infected aerosols. A previous study had revealed a
      hyperendemic focus in South France. A case-control study was carried-out in this
      area from 1996 to 1999. Besides the role of wind, this study stressed out the
      exposure to a pedagogical farm as an independent risk factor (4.7% of cases - 0
      controls): Exposure to sheep and new-born animals (OR: 3.07 and 4.01
      respectively) were not significant after omission of people exposed to the
      pedagogical farm. Such farms are visited by people who would not have any other
      contact with farm animals. These farms require a drastic hygiene and control. Q
      fever, as a public health problem, still requires further studies to identify and
      confirm individual behavioral risk factors.

PMID- 16284876
TI  - Changes in the urine composition during its passage through the ureter. A concept
      of urothelial function.
AB  - Studies in our and other laboratories have negated the general assumption that
      the urothelium functions as a simple conduit and support the concept of a dynamic
      urothelium. Based on this concept, we investigated the hypothesis that urine
      undergoes changes during its passage in the ureter. Urine samples were separately
      collected from the renal pelvis and ureters of 23 volunteers (15 men, eight
      women, mean age 37.6 years) through cutaneous ureterostomy performed as a
      treatment for bladder cancer. The pH was determined using a pH electrode,
      osmolality by means of micro-osmometry and Na and K by flame photometry. The pH
      and osmolality of ureteric urine showed no significant differences from renal
      pelvic urine, whereas the Na and K levels of the ureteric urine were
      significantly increased (both P<0.05). Gender and age differences were not
      significant. Renal pelvic urine undergoes changes in Na and K concentrations
      during its passage through the ureter. These findings presumably indicate that
      the ureteral urothelium is a functioning epithelium and that the renal pelvic and
      ureteric urine are not identical.

PMID- 16284875
TI  - Efficient differentiation of Mycobacterium tuberculosis strains of the W-Beijing
      family from Russia using highly polymorphic VNTR loci.
AB  - The W-Beijing family is a widespread Mycobacterium tuberculosis clonal lineage
      that frequently causes epidemic outbreaks. This family is genetically homogeneous
      and conserved, so ETR-VNTR (exact tandem repeat-variable number of tandem
      repeats) typing is insufficient for strain differentiation, due to a common ETR-A
      to E profile (42435). This leads to the false clustering in molecular
      epidemiological studies, especially in the regions of predominance of the W
      Beijing family. In this study, we searched for VNTR loci with a high evolutionary
      rate of polymorphism in the W-Beijing genome. Here we further evaluated VNTR
      typing on a set of 99 Mycobacterium tuberculosis clinical isolates and reference
      strains. These isolates were characterized and classified into several genotype
      families based on three ETR loci (A, C, E) and eight additional loci [previously
      described as QUB (Queen's University Belfast) or MIRU (Mycobacterial Interspersed
      Repetitive Units) or Mtubs]. Ninety-nine strains were divided into 74 VNTR-types,
      51 isolates of the W-Beijing family identified by IS6110 RFLP-typing (the
      restriction fragment length polymorphism-typing) and/or spoligotyping were
      subdivided into 30 VNTR-types. HGDI (the Hunter-Gaston discriminatory index) for
      all studied loci was close to that of IS6110 RFLP typing, a "gold standard"
      method for subtyping M. tuberculosis complex strains. The QUB 26 and QUB 18 loci
      located in the PPE genes were highly polymorphic and more discriminative than
      other loci (HGDI is 0.8). Statistically significant increase of tandem repeats
      number in loci ETR-A, -E, QUB 26, QUB 18, QUB 11B, Mtub21 was revealed in the W
      Beijing group compared to genetically divergent non-W-Beijing strains. Thirty-six
      isolates were subjected to IS6110 RFLP typing. The congruence between results of
      the IS6110 RFLP typing and 11-loci VNTR typing was estimated on 23 isolates of
      the W-Beijing family. These isolates were subdivided into 9 IS6110-RFLP types and
      13 VNTR types. The poor profiles correlation (0.767) reflects the differences in
      the rate and type of evolution between genome regions targeted by IS6110-RFLP and
      VNTR typing. VNTR typing in proposed format is powerful tool for discrimination
      of M. tuberculosis strains with different level of genetic relationship.

PMID- 16284877
TI  - Oxalate degrading bacteria: new treatment option for patients with primary and
      secondary hyperoxaluria?
AB  - Current treatment options in patients with primary and secondary hyperoxaluria
      are limited and do not always lead to sufficient reduction in urinary oxalate
      excretion. Intestinal oxalate degrading bacteria are capable of degrading oxalate
      to CO(2) and formate, the latter being further metabolized and excreted via the
      feces. It is speculated, that both endogenously produced, as well as dietary
      oxalate can be significantly removed via the intestinal tract. Oxalobacter
      formigenes, an obligate anaerobic microbe normally found in the intestinal tract
      has one oxalate degrading enzyme, oxalyl-CoA decarboxylase, which is also found
      in Bifidobacterium lactis. Other bacteria with possible oxalate degrading potency
      are lactic acid bacteria, as well as Enterococcus faecalis and Eubacterium
      lentum. However, specific therapeutic studies on humans are scarce and, except
      for Oxalobacter, data are not congruent. We found the oral application of
      Oxalobacter successful in patients with primary hyperoxaluria. However, long-term
      post-treatment follow-up of 1-2 years showed that constant intestinal
      colonization is not achieved in most patients. In one patient with constant
      colonization, urinary oxalate excretion normalized over time. Short-term studies
      with other bacteria such as lactic acid bacteria did not show a specific
      reduction in urinary oxalate excretion. O. formigenes might be a promising new
      therapeutic tool in patients with primary and secondary hyperoxaluria.

PMID- 16284878
TI  - The role of preemptive liver transplantation in primary hyperoxaluria type 1.
AB  - In primary hyperoxaluria the deficiency or mistargeting of hepatic alanine
      glyoxylate aminotransferase (AGT) leads to the overproduction of oxalate
      resulting in hyperoxaluria and renal damage due to urolithiasis and/or
      nephrocalcinosis. Presently, the cure of the metabolic defect can be achieved
      only by liver transplantation. While for patients with end-stage renal disease
      combined hepatorenal transplantation is recommended, the concept of preemptive
      liver transplantation (PLTX), i.e. cure of the metabolic defect before renal
      damage occurs, has received considerable attention. Due to the heterogenous
      clinical course in PH1, optimal timing of PLTX is a matter of debate. Advocators
      of PLTX would consider a patient with a slowly declining GFR, reaching levels of
      40-60 ml/min/1.73 m(2), as an ideal candidate, while others would continue
      medical treatment in these patients and opt for rapid combined liver-kidney
      transplantation if GFR reaches even lower levels. This review will discuss the
      background and rationale of PLTX and gives an update on 11 patients with PLTX who
      have been reported in the literature to date.

PMID- 16284879
TI  - Renal cell adaptation to oxalate.
AB  - Renal manifestations of chronic hyperoxaluria include nephrolithiasis and, when
      extreme, interstitial scarring and progressive loss of function. Exposure of
      cultured renal cells to oxalate has been reported to cause cell death, as well as
      proliferation. The current study was performed to assess the time course and cell
      type specificity of these responses. Proximal (LLC-PK(1)) and distal [cIMCD and
      primary human renal (HRC1)] renal epithelial cells, as well as interstitial KNRK
      cells, were exposed to oxalate (0.5-2.0 mM) for 24-72 h. The generation of
      reactive oxygen species (ROS) was measured using the fluorescent probe DCF, and
      cell number was determined with CyQuant reagent. HSP-70 expression was assessed
      via real time PCR and quantitative Western blot. In response to all oxalate
      concentrations (0.5-2.0 mM) and lengths of exposure (15 min-2 h), cultured
      proximal and distal renal epithelial cells and renal fibroblasts generated ROS.
      After 24 h, cells demonstrated initial cell death and decrease in cell numbers,
      but by 48-72 h adapted and grew, despite the continued presence of oxalate. This
      response was associated with increased expression of HSP-70 mRNA and protein.
      Renal cells in vivo may possess adaptive mechanisms to withstand chronic
      hyperoxaluria, including increased expression of chaperone molecules such as HSP
      70.

PMID- 16284880
TI  - Quantitation of stone burden: imaging advances.
AB  - The accurate diagnosis and quantitation of nephrolithiasis in patients with
      primary hyperoxaluria (PH) often directly impacts the medical and surgical
      management for individuals with both symptomatic and asymptomatic calculi.
      Traditionally, depiction of the size, location and appearance of urinary calculi
      has been provided by kidney, ureter and bladder plain film radiographs with or
      without tomography. Given advances in imaging technology there is a shift from
      conventional radiographs to cross-sectional imaging technology, namely unenhanced
      computed tomography (CT), CT urography, ultrasound and magnetic resonance
      imaging. These diagnostic techniques provide differing advantages and
      disadvantages for imaging stone disease. This review outlines imaging advances in
      the accurate diagnosis and quantitation of patients with metabolically active
      stone disease such as PH.

PMID- 16284881
TI  - A new animal model of hyperoxaluria and nephrolithiasis in rats with small bowel
      resection.
AB  - An association between small bowel resection and stone disease has been noted,
      which is primarily due to increased gut oxalate absorption and resulting
      excretion by the kidney. In order to better understand the factors affecting both
      oxalate absorption and renal excretion, and the resulting renal lesions, we have
      developed a rodent model of small bowel resection and hyperoxaluria. Using this
      model, we have studied the renal histology in animals with hyperoxaluria over
      time spans from 2 weeks to 7 months. The initial lesion appears to be crystal
      formation along the brush border of the proximal tubule, with eventual crystal
      deposition in collecting ducts and papillary interstitium, and eventual tubule
      obstruction, interstitial inflammation and fibrosis. Crystal formation appears to
      dissociate from urinary supersaturation. We hypothesize that oxalate transporters
      in the proximal tubule may increase local saturations, leading to crystal
      formation at this site initially. Further studies are required to better
      characterize the causes and consequences of hyperoxaluria in this animal model.

PMID- 16284882
TI  - Effects of luminal oxalate or calcium oxalate on renal tubular cells in culture.
AB  - Oxalate or calcium oxalate crystal-induced tissue damage could be conducive to
      renal stone disease. We studied the response of renal proximal (LLC-PK1 and MDCK
      II) and collecting (RCCD1 and MDCK-I) tubule cell lines to oxalate ions as well
      as to calcium oxalate monohydrate (COM) crystals. Cells grown on tissue culture
      plastic or permeable growth substrates were exposed to high (1 mM) and extremely
      high (5 and 10 mM) oxalate concentrations, or to a relatively large quantity of
      crystals (146 microg), after which cell morphology, prostaglandin E(2) (PGE(2))
      secretion, [(3)H]thymidine incorporation, total cell numbers and various forms of
      cell death were studied. Morphological alterations, increased PGE(2) secretion,
      elevated levels of DNA synthesis and necrotic cell death were induced by
      extremely high, but not by high oxalate. Crystals were rapidly internalized by
      proximal tubular cells, which stimulated PGE(2) secretion and DNA synthesis and
      the release of crystal-containing necrotic cells from the monolayer. Crystals did
      not bind to, were not taken up by, and did not cause marked responses in
      collecting tubule cells. These results show that free oxalate is toxic only at
      supraphysiological concentrations and that calcium oxalate is toxic only to renal
      tubular cells that usually do not encounter crystals. Based on these results, it
      is unlikely that oxalate anions or calcium oxalate crystals are responsible for
      the tissue damage that may precede renal stone formation.

PMID- 16284883
TI  - Oxalate toxicity in renal cells.
AB  - Exposure to oxalate, a constituent of the most common form of kidney stones,
      generates toxic responses in renal epithelial cells, including altered membrane
      surface properties and cellular lipids, changes in gene expression, disruption of
      mitochondrial function, formation of reactive oxygen species and decreased cell
      viability. Oxalate exposure activates phospholipase A2 (PLA2), which increases
      two lipid signaling molecules, arachidonic acid and lysophosphatidylcholine (Lyso
      PC). PLA2 inhibition blocks, whereas exogenous Lyso-PC or arachidonic acid
      reproduce many of the effects of oxalate on mitochondrial function, gene
      expression and cell viability, suggesting that PLA2 activation plays a role in
      mediating oxalate toxicity. Oxalate exposure also elicits potentially adaptive or
      protective changes that increase expression of proteins that may prevent crystal
      formation or attachment. Additional adaptive responses may facilitate removal and
      replacement of dead or damaged cells. The presence of different inflammatory
      cells and molecules in the kidneys of rats with hyperoxaluria and in stone
      patients suggests that inflammatory responses play roles in stone disease. Renal
      epithelial cells can synthesize a variety of cytokines, chemoattractants and
      other molecules with the potential to interface with inflammatory cells;
      moreover, oxalate exposure increases the synthesis of these molecules. The
      present studies demonstrate that oxalate exposure upregulates cyclooxygenase-2,
      which catalyzes the rate-limiting step in the synthesis of prostanoids, compounds
      derived from arachidonic acid that can modify crystal binding and may also
      influence inflammation. In addition, renal cell oxalate exposure promotes rapid
      degradation of IkappaBalpha, an endogenous inhibitor of the NF-kappaB
      transcription factor. A similar response is observed following renal cell
      exposure to lipopolysaccharide (LPS), a bacterial cell wall component that
      activates toll-like receptor 4 (TLR4). While TLRs are primarily associated with
      immune cells, they are also found on many other cell types, including renal
      epithelial cells, suggesting that TLR signaling could directly impact renal
      function. Prior exposure of renal epithelial cells to oxalate in vitro produces
      endotoxin tolerance, i.e. a loss of responsiveness to LPS and conversely, prior
      exposure to LPS elicits a similar heterologous desensitization to oxalate. Renal
      cell desensitization to oxalate stimulation may have profound effects on the
      outcome of renal stone disease by impairing protective responses.

PMID- 16284884
TI  - NF-kappaB and chemokine-cytokine expression in renal tubulointerstitium in
      experimental hyperoxaluria. Role of the renin-angiotensin system.
AB  - Recent evidence indicates that the renin-angiotensin system (RAS) seems to play a
      considerable role in the development of tubulointerstitial (TI) lesions caused by
      hyperoxaluria (Hox). The purpose of the present study was to evaluate the
      specific mechanism by which Hox involving RAS induces chemokine and cytokine
      expression and, therefore, renal TI damage in the ethylene-glycol (ETG) induced
      hyperoxaluric rat model. Sprague-Dawley rats, separated into five groups,
      received: G1 regular water, and G2, G3, G4 and G5 1% ETG (a precursor for
      oxalates) in their drinking water for 4 weeks. An angiotensin converting enzyme
      inhibitor, benazepril (BZ) 10 mg/kg/day, angiotensin II receptor antagonists,
      subtype 1 (AT1) losartan (LOS) 40 mg/kg/day and subtype 2 (AT2) PD 123,319 (PD)
      10 mg/kg/day, were administered daily to G3, G4 and G5, respectively. At the end
      of the study, the inflammatory response to Hox was evaluated using anti-NF-kappaB
      (p50), anti-IL-6, anti-MCP-1; anti-RANTES and anti-ED1 (monocytes/macrophages) in
      each group. In spite of the same urine oxalate levels, rats belonging to the
      hyperoxaluric groups treated with either BZ or LOS showed significantly (P<0.01)
      less TI lesions together with a lower immunoexpression of inflammatory mediators
      when compared with untreated hyperoxaluric animals. NF-kappaB (p50) was increased
      in tubular cells in the ETG group (43.6+/-8.7 positive cells/mm(2)) and was
      significantly (P<0.01) reduced by LOS (11.2+/-4 positive cells/mm(2)) and even
      more by BZ (6.1+/-2.4 positive cells/mm(2)). There was a significant (P<0.01)
      correlation between NF-kappaB (p50) positive cells and ED1 cells in the ETG group
      (r=0.88) and in the ETG+LOS group (r=0.92). LOS showed better control on IL-6 and
      MCP-1 with respect to untreated rats, while BZ showed the best control on RANTES
      and ED1 cells in comparison with untreated animals. Renal function was
      significantly (P<0.01) better preserved in BZ and LOS treated groups compared to
      both untreated animals and rats with PD, as indicated by creatinine clearance
      values. These results suggest that Hox stimulates the NF-kappaB cascade and,
      therefore, induces the overexpression of inflammatory mediators like IL-6, MCP-1,
      and RANTES. This pathway seems to be mediated not only by AT1 but also by AT2
      receptors of angiotensin II.

PMID- 16284885
TI  - Pitfalls in the management of patients with primary hyperoxaluria: a urologist's
      perspective.
AB  - The primary hyperoxalurias are rare, inherited diseases which commonly manifest
      early in life as urolithiasis. As these patients often present to the urologic
      surgeon, it is imperative that urologists understand the typical presentation,
      diagnosis, and management of urolithiasis associated with primary hyperoxaluria.
      In this review, the pertinent epidemiology and pathogenesis as they relate to the
      diagnosis and natural history of the disease are discussed. The literature on
      therapeutic options for primary hyperoxaluric patients with calculi is examined,
      and treatment strategies are suggested.

PMID- 16284887
TI  - Surveillance colonoscopy in individuals at risk for hereditary nonpolyposis
      colorectal cancer: an evidence-based review.
AB  - PURPOSE: Surveillance colonoscopy plays an important role in the management of
      asymptomatic patients known to carry and suspected of carrying hereditary
      nonpolyposis colorectal cancer gene mutations. Although the shortest interval
      between surveillance examinations may seem to offer the most benefit to patients,
      excessive use of this procedure may have unwanted consequences. This study was
      designed to evaluate the evidence and make recommendations regarding the optimal
      frequency of surveillance colonoscopy and the age at which to initiate
      surveillance based on the best available evidence. METHODS: MEDLINE was searched
      for all articles assessing surveillance colonoscopy from 1966 to 2004 by using
      the MESH terms "hereditary nonpolyposis colorectal cancer" and "screening." The
      evidence was systematically reviewed and a critical appraisal of the evidence was
      performed. RESULTS: There are no randomized, controlled, clinical trials
      examining the frequency of surveillance colonoscopy in hereditary nonpolyposis
      colorectal cancer. Three cohort studies were identified for review. There is one
      cohort study of good quality that provides evidence that surveillance colonoscopy
      every three years in patients with hereditary nonpolyposis colorectal cancer
      reduces the risk of developing colorectal cancer and the risk of death. The two
      remaining cohort studies provide poor evidence on which to make a recommendation.
      CONCLUSIONS: The best available evidence supports surveillance with complete
      colonoscopy to the cecum every three years in patients with hereditary
      nonpolyposis colorectal cancer (B recommendation). There is no evidence to
      support or refute more frequent screening. Further research is required to
      examine the potential harms and benefits of more frequent screening. However,
      given the potential for rapid progression from adenoma to carcinoma and missing
      lesions at colonoscopy, there is consensus that screening more frequently than
      every three years is required.

PMID- 16284905
TI  - Proceedings of the 2nd International Meeting on Multiple System Atrophy, June 17
      18, 2004, Rome, Italy.

PMID- 16284906
TI  - Epidemiological evidence on multiple system atrophy.
AB  - Multiple system atrophy (MSA), is a sporadic neurodegenerative disorder
      characterized clinically by any combination of parkinsonian, autonomic,
      cerebellar or pyramidal symptoms and signs. The frequence of disease is estimated
      for the incidence rate to 0.6 cases per 100.000 person-years, while the
      prevalence rate is included between 1.86 and 4.9 cases per 100.000 pop. A risk
      factor seems to be the occupational history of farming also if the occupational
      exposure to pesticides is not associated with MSA. Smoking is probably a
      protective factor in MSA as Parkinson's disease. MSA seems a sporadic disease
      also if recently a German family with two MSA cases has been reported. The
      polymorphism association studies support a role for inflammation-related genes in
      risk for MSA. The current epidemiological and clinical evidence suggests that
      likely the etiopathogenesis of MSA is complex, and that many genetic as well as
      environmental factors are involved. Unfortunately, the most of studies in MSA are
      lacking in a sample size estimate to test the hypothesis, then the scientific
      evidence is poor. Then, much larger numbers of cases and controls are necessary
      for these studies to reach sufficient power, but collecting such large numbers is
      feasible only in the framework of multicentric consortia.

PMID- 16284907
TI  - Absence of alpha-synuclein mRNA expression in normal and multiple system atrophy
      oligodendroglia.
AB  - alpha-Synuclein is a major constituent of glial cytoplasmic inclusions (GCIs),
      which are pathognomic for multiple system atrophy (MSA). We have previously
      demonstrated that in normal human brain, alpha-synuclein mRNA has a restricted
      pattern of neuronal expression and no apparent glial expression. The current
      study used double-label in situ hybridization to determine if alpha-synuclein
      mRNA is expressed by oligodendroglia of MSA cases. Analysis of MSA brain tissue
      revealed depletion of regional signal for this transcript in many brain areas due
      to extensive neurodegeneration. Cellular analysis of oligodendroglia in crus
      cerebri, a GCI-rich region ventral to substantia nigra, revealed an absence of
      alpha-synuclein mRNA signal in control and MSA cases. However, an abundance of
      this transcript was detected in melanin-containing neurons of substantia nigra.
      Therefore, oligodendroglia do not express alpha-synuclein mRNA in control and MSA
      cases suggesting that involvement of alpha-synuclein in GCI pathology of MSA is
      due to its ectopic presence in oligodendroglia.

PMID- 16284909
TI  - How to diagnose MSA early: the role of sphincter EMG.
AB  - Multiple system atrophy (MSA) is a degenerative disease manifesting a combination
      of parkinsonism, cerebellar, pyramidal, and autonomic (including urinary, sexual
      and anorectal) dysfunction. It is pathomorphologically defined, but lacks a
      definitive clinical diagnostic test. In patients with probable MSA, abnormal
      sphincter EMG, as compared to control subjects, has been found in the majority of
      patients in all the different forms of the disease in most studies, including
      patients who, as yet, have no urological or anorectal problems. Patients with
      Parkinson's disease (PD) as a rule do not show marked sphincter EMG abnormalities
      in the first five years of the disease. Thus, abnormal spontaneous activity or
      marked motor unit potential changes in sphincter muscles are helpful in
      distinguishing MSA from PD in the first five years after the onset of symptoms
      and signs, and from pure autonomic failure, as well as from cerebellar ataxias,
      if other causes for sphincter denervation have been ruled out. EMG does not
      distinguish MSA from progressive supranuclear palsy. How early in the course of
      MSA these abnormalities become significant enough to support diagnosis remains to
      be established by prospective studies.

PMID- 16284908
TI  - Brain SPECT imaging in multiple system atrophy.
AB  - Clinical diagnosis of multiple system atrophy (MSA) relays on signs and symptoms
      that are often difficult to identify particularly at early stage. Indeed
      neuropathological studies have demonstrated that MSA is the first cause of
      misdiagnosis in a cohort of patients presenting with parkinsonian features.
      Dopamine transporter imaging (DAT) shows striatal decrements in both MSA and
      Parkinson's disease (PD) making it not sensitive for differential diagnosis.
      Studies of dopamine D2 receptors with IBZM may help revealing striatal
      degeneration but a large overlap exist particularly if PD patients with advanced
      disease are included. We have measured brain flow with technetium-99m ethyl
      cysteinate dimer (ECD-SPECT) in 36 MSA patients and compared it with 43 PD and 39
      age-matched controls. Using Statistical Parametric Mapping (SPM99) we found areas
      of significant reduced perfusion in the striatum, brain stem and cerebellum in
      MSA compared to the other groups. We believe that ECD-SPECT imaging may offer
      significant advantages compared to other imaging techniques in the assessment of
      neuronal degeneration in MSA and may help the clinician in the diagnostic
      characterization of patients presenting with atypical parkinsonism.

PMID- 16284910
TI  - The North American Multiple System Atrophy Study Group.
AB  - The North American Multiple System Atrophy Study Group involves investigators in
      12 US medical centers funded by a grant from the National Institutes of Health.
      The objectives are to examine the environmental and genetic risk factors for MSA;
      elucidate pathogenic mechanisms underlying the disorder; and refine evaluations
      used for assessment. During its first year, the group enrolled 87 patients,
      implemented four cores, and initiated four scientific projects. Most patients
      among the 87 had parkinsonian features, which frequently began asymmetrically and
      remained asymmetrical; one-third responded to levodopa and many developed
      levodopa complications; almost two-thirds of the patients had cerebellar
      dysfunction, of these 90% had ataxia; urinary incontinence occurred commonly, and
      sleep disorders affected most. The investigators studied the effects of oxidative
      and nitrative stress upon the formation of alpha-synuclein inclusions; generated
      transgenic models of alpha-synuclein accumulation that recapitulate several
      behavioral and neuropathological features of MSA; and compared the severity of
      the autonomic features of MSA, Parkinson's disease and dementia with Lewy bodies.

PMID- 16284911
TI  - Management of multiple system atrophy: state of the art.
AB  - Multiple system atrophy (MSA) is a sporadic neurodegenerative disease of
      undetermined aetiology presenting with parkinsonian, autonomic, cerebellar, and
      pyramidal signs. Despite the lack of any effective therapy to reverse MSA, some
      of the symptoms may be improved with adequate symptomatic therapies. Medical
      treatment is largely aimed at mitigating the parkinsonian and autonomic features.
      The therapeutic results of levodopa therapy in cases of MSA are difficult to
      interpret because of their variability. Nevertheless, the simple statement that
      patients with MSA do not respond to levodopa is false. Clinical and
      pathologically proven series document levodopa efficacy in about 40-60% of
      patients with MSA and predominant parkinsonian features. Other antiparkinsonian
      compounds (dopamine agonists, amantadine) may also be employed, but they are not
      more effective than levodopa. Orthostatic hypotension (OH) can be suspected from
      the patient s history and subsequently documented in the clinic by measuring
      lying and standing blood pressure. The diagnosis ideally should be confirmed with
      additional laboratory tests to determine the cause and evaluate the functional
      deficit, so as to aid treatment. A number of pharmacological agents with
      different mechanisms of action have been used in MSA to reduce OH when this is
      symptomatic. OH can also be alleviated by avoiding aggravating factors, such as
      the effects of food, micturition, exposure to a warm environment, and
      physiological diurnal changes, and by using other non-pharmacological strategies.
      The treatment of the very common genitourinary symptoms (incontinence, retention,
      impotence) should also be considered in order to improve the quality of life of
      these patients.

PMID- 16284913
TI  - A longitudinal model for non-monotonic clinical assessment scale data.
AB  - Clinical assessment scales, where subitem ratings are added and summarized as a
      total score, are convenient tools for monitoring disease progression and often
      used to measure the effect of drug treatment in clinical trials. Statistical
      evaluation of any beneficial treatment effects tends to focus on single-valued
      summary measures, for example, the difference between the score at the end of
      treatment and the score at baseline. Such analyses ignore potentially important
      features of the data, e.g. early vs. late recoveries. It is therefore of interest
      to develop longitudinal models that make more efficient use of the information
      present in non-monotonic clinical assessment scale data. We propose a two-part
      modeling approach for the modeling of this type of data. Non-monotonicity is
      managed by regarding score changes as Markovian transition events. A set of
      probabilistic models are used to describe the occurrences of the transitions.
      Continuous models are used to describe the magnitude of the scale score change,
      given the observed transition. In this manner, a non-monotonic disease
      progression is handled more efficiently than if other available methods are used.
      We illustrate this approach using data from a recent phase II study of a drug
      used in the treatment of stroke, where stroke severity was measured on the
      Scandinavian Stroke Scale (SSS). This scale consists of nine subitems:
      consciousness, eye movements, hand/arm/leg motor performance, orientation,
      speech, facial palsy, and gait. The data were non-monotonic, since there was at
      any time a risk of a score decline, despite a general tendency towards healing.
      The two-part probabilistic/continuous model fit the data well and proved to be
      robust in model-checking procedures such as posterior predictive checks and
      bootstrapping. The models derived using this approach could potentially
      accommodate drug effects, not only in terms of score improvement at end of study,
      but also on the onset of recovery, on dropout and on the probability of
      unfavorable progression patterns. In addition, it is possible to use the
      resulting for simulation of the prospective outcome of future studies. We
      conclude that this approach has considerable potential for more efficient use of
      information in longitudinal modeling of non-monotonic clinical assessment scale
      data.

PMID- 16284912
TI  - Dependence of visual cell properties on intracortical synapses among
      hypercolumns: analysis by a computer model.
AB  - The role of intracortical synapses in affecting the property of visual cells is
      investigated by means of an original mathematical model of cortical circuitry in
      V1. The model represents a compromise between computational simplicity and
      physiological reliability. The model incorporates four different inputs into a
      cortical cell: thalamic input from the lateral geniculate nucleus, according to
      an even Gabor function; short-range inhibition confined within the hypercolumn; a
      long-range excitation, which emphasizes the properties of the input; and a long
      range inhibition. In the model we assume that all cells receive a similar
      thalamic input, which differs simply according to its position in the retina and
      orientation preference. Simulations were performed, with different parameter
      values, to assess the main characteristics of cell response (i.e., the width and
      locations of subregions in the receptive field (RF), orientation tuning curve,
      and response to drifting and counterphase gratings) as a function of the strength
      and extension of intracortical excitatory synapses. Results suggest that, if
      intracortical excitation is confined within the hypercolumn, the cells exhibit
      the same properties as simple cells, both with regards to the width and shape of
      the RF, orientation tuning curve, and response to drifting and counterphase
      gratings. By contrast, if excitatory synapses extend beyond the hypercolumn with
      sufficient strength, the cells exhibit the typical characteristics of complex
      cells. A progressive shift from complex to simple cells can be realized with a
      monotonic variation in parameters. Simulations are also performed with a
      hierarchical model, to suggest possible experiments able to discriminate the
      present recurrent mechanism from the classical hierarchical one. Results support
      the assumptions of previous simpler models (Chance et al., 1999) and may help to
      understand and assess the role of intracortical synapses in rigorous quantitative
      terms.

PMID- 16284914
TI  - Sample size computations for PK/PD population models.
AB  - We describe an accurate, yet simple and fast sample size computation method for
      hypothesis testing in population PK/PD studies. We use a first order
      approximation to the nonlinear mixed effects model and chi-square distributed
      Wald statistic to compute the minimum sample size to achieve given degree of
      power in rejecting a null hypothesis in population PK/PD studies. The method is
      an extension of Rochon's sample size computation method for repeated measurement
      experiments. We compute sample sizes for PK and PK/PD models with different
      conditions, and use Monte Carlo simulation to show that the computed sample size
      retrieves the required power. We also show the effect of different sampling
      strategies, such as minimal, i.e., as many observations per individual as
      parameters in the model, and intensive on sample size. The proposed sample size
      computation method can produce estimates of minimum sample size to achieve the
      desired power in hypothesis testing in a greatly reduced time than currently
      available simulation-based methods. The method is rapid and efficient for sample
      size computation in population PK/PD study using nonlinear mixed effect models.
      The method is general and can accommodate any type of hierarchical models.
      Simulation results suggest that intensive sampling allows the reduction of the
      number of patients enrolled in a clinical study.

PMID- 16284916
TI  - Population pharmacokinetics of the active metabolite of leflunomide in pediatric
      subjects with polyarticular course juvenile rheumatoid arthritis.
AB  - Leflunomide is a pyrimidine synthesis inhibitor used in the treatment of
      rheumatoid arthritis. Data from two clinical studies were used to establish a
      population pharmacokinetic (PPK) model for the active metabolite (M1) of
      leflunomide in patients with juvenile rheumatoid arthritis (JRA) and determine
      appropriate pediatric doses. Seventy-three subjects 3-17 years of age provided
      674 M1 concentrations. The PPK model was derived from nonlinear mixed-effects
      modeling and qualified by cross-study evaluation and predictive check. A one
      compartment model with first-order input described M1 PPK well. Body weight (WT)
      correlated weakly with oral clearance (CL/F = 0.020.[WT/40](0.430)) and strongly
      with volume of distribution (V/F = 5.8.[WT/40](0.769)). Steady-state
      concentrations (C(ss)) of M1 in JRA were compared for a variety of leflunomide
      dose regimens using Monte-Carlo simulation. To achieve comparable C(ss) values in
      pediatric patients with JRA to that in adult patients, doses of leflunomide
      should be adjusted modestly: 10 mg/d for 10-20 kg, 15 mg/d for 20-40 kg, and 20
      mg/d for > 40 kg.

PMID- 16284917
TI  - Some considerations on the design of population pharmacokinetic studies.
AB  - The goal of this manuscript is to introduce a framework for consideration of
      designs for population pharmacokinetic orpharmacokinetic-pharmacodynamic studies.
      A standard one compartment pharmacokinetic model with first-order input and
      elimination is considered. A series of theoretical designs are considered that
      explore the influence of optimizing the allocation of sampling times, allocating
      patients to elementary designs, consideration of sparse sampling and unbalanced
      designs and also the influence of single vs. multiple dose designs. It was found
      that what appears to be relatively sparse sampling (less blood samples per
      patient than the number of fixed effects parameters to estimate) can also be
      highly informative. Overall, it is evident that exploring the population design
      space can yield many parsimonious designs that are efficient for parameter
      estimation and that may not otherwise have been considered without the aid of
      optimal design theory.

PMID- 16284915
TI  - The acute disposition of (R)- and (s)-methadone in brain and lung of sheep.
AB  - The cerebral and lung kinetics of the enantiomers of methadone were quantified
      using a conscious chronically instrumented sheep preparation, as these organs are
      the major organs governing the peak brain concentrations (and therefore effects)
      of methadone after ivbolus administration. Seven sheep were administered
      intravenous infusions of rac-methadone (30 mg over 4 min). Whole blood (R)- and
      (S)-methadone concentrations were measured using stereoselective HPLC. Methadone
      transiently increased cardiac output (CO) and mean arterial pressure, but did not
      alter cerebral blood flow (CBF) or cause significant respiratory depression.
      Using physiologically based kinetic models, cerebral kinetics were inferred from
      arterio-sagittal sinus concentration gradients and CBF, lung kinetics from
      pulmonary artery-aortic gradient and CO. Lung and cerebral kinetics were best
      described by a partially membrane-limited model for both enantiomers. Lung
      kinetics displayed clear stereoselectivity, due to the smaller apparent volume of
      the deep lung compartment for (R)-methadone (45 l) compared to (S)-methadone (79
      l). This resulted in systemic differences in the concentrations of the
      enantiomers. Minimal stereoselectivity was observed in cerebral kinetics. The
      brain:blood equilibration of methadone was slow (half-life of 18 min) due to
      intermediate permeability and large apparent cerebral distribution volumes.
      However, the permeability term was sufficiently high that cerebral kinetics were
      affected by CBF. Simulations demonstrated that if CBF was doubled, the
      equilibration half-life of methadone with brain tissue decreased by 30%, and
      there was a 25% increase in the peak brain concentrations. Future studies are
      needed to confirm the role of cerebral blood flow alterations in the exposure of
      the brain to methadone, especially in the case of respiratory depression. In
      conclusion, pharmacokinetic modelling of methadone confirmed a large
      equilibration delay between brain and blood.

PMID- 16284918
TI  - Pharmacokinetic modelling of 5-FU production from capecitabine--a population
      study in 40 adult patients with metastatic cancer.
AB  - AIMS: To model the biotransformation steps of 5-FU production from capecitabine
      and identify patient characteristics that may influence the drug disposition.
      METHODS: Blood samples and demographic data were collected from two phase I
      studies in which adult patients received oral capecitabine for various
      malignancies. Capecitabine, 5'-deoxy-5-fluorocytidine (5'-DFCR), 5'-deoxy-5
      fluorouridine (5'-DFUR) and 5-fluorouracile (5-FU) concentration-time data were
      analysed via a population approach using NONMEM. RESULTS: Forty patients and 75
      pharmacokinetic time-courses were available for analysis. Capecitabine
      pharmacokinetics was ascribed to a one compartment model from which 5'-DFCR, 5'
      DFUR and 5-FU were sequentially produced. Capecitabine oral absorption was
      characterized by a rapid first order input (K(a)=2.1 +/- 0.3 hr(-1)) with a lag
      time (0.28 +/- 0.11 hr), but related inter-occasion (IOV) and inter-subject (ISV)
      variabilities for these parameters, 167% and 110%, indicated that this oral
      absorption was highly variable. The capecitabine CL (CL10 = 218+/- 18 L/hr, ISV =
      18%) and 5'-DFUR elimination rate constant (K34 = 5.3 +/- 2.0 hr(-1), ISV = 25%)
      were influenced by total bilirubin (BILT). The elimination rate constant of
      plasma 5-FU (K40) was 66 +/- 24 hr(-1) (ISV = 34%). The final pharmacokinetic
      model was validated using 2000 bootstrap runs and provided non-parametric
      statistics of the parameters (median, 2.5th and 97.5th percentiles). CONCLUSIONS:
      This study supported the possibility of modelling a complex sequential metabolic
      pathway which produces pharmacologicaly active compounds from a prodrug. Only
      BILT significantly influenced the pharmacokinetics but this effect was not
      considered as relevant for dosing adjustment.

PMID- 16284919
TI  - Prediction discrepancies for the evaluation of nonlinear mixed-effects models.
AB  - Reliable estimation methods for non-linear mixed-effects models are now available
      and, although these models are increasingly used, only a limited number of
      statistical developments for their evaluation have been reported. We develop a
      criterion and a test to evaluate nonlinear mixed-effects models based on the
      whole predictive distribution. For each observation, we define the prediction
      discrepancy (pd) as the percentile of the observation in the whole marginal
      predictive distribution under H(0). We propose to compute prediction
      discrepancies using Monte Carlo integration which does not require model
      approximation. If the model is valid, these pd should be uniformly distributed
      over (0, 1) which can be tested by a Kolmogorov-Smirnov test. In a simulation
      study based on a standard population pharmacokinetic model, we compare and show
      the interest of this criterion with respect to the one most frequently used to
      evaluate nonlinear mixed-effects models: standardized prediction errors (spe)
      which are evaluated using a first order approximation of the model. Trends in pd
      can also be evaluated via several plots to check for specific departures from the
      model.

PMID- 16284920
TI  - Pharmacodynamic analysis of changes in reticulocyte subtype distribution in
      phlebotomy-induced stress erythropoiesis.
AB  - Changes in the reticulocyte subtype distribution (high, medium and low
      reticulocytes count (HR, MR, LR)) measured by flow cytometry following phlebotomy
      induced stress erythropoiesis (abruptly dropping hemoglobin to 3-4 g/dl over 4-5
      hr) and the pharmacodynamic (PD) relationship to the stimulated erythropoietin
      (EPO) was investigated in sheep. A PD model was developed that describes the
      relationship between EPO and the reticulocyte maturity distribution fractions
      (r=0.95+/-0.02, mean +/- SD). The lag-time between EPO activation of erythroid
      progenitor cells and the subsequent increase in the least mature HR fraction in
      the peripheral circulation was 0.72 +/- 0.08 days. The mean transition times (in
      days) for all three reticulocyte fractions changed at baseline from, T(HR) : 0.09
      +/- 0.06, T(MR) : 0.06 +/- 0.04, and T(LR) : 0.46 +/- 0.24 to T(HR) : 0.13 +/-
      0.08, T(MR) : 0.29 +/- 0.15, and T(LR) : 2.3 +/- 0.24 under stress
      erythropoiesis. The total mean residence time for a reticulocyte in the
      peripheral circulation, T(total) (T(HR) + T(MR) + T(LR)), increased from 0.60 +/-
      0.33 days under basal to 2.8 +/- 0.09 days during stress erythropoiesis. The
      statistically significant increase observed for T(LR) and T(total) supports the
      hypothesis that stress erythropoiesis perturbs the mean reticulocyte transition
      times. A correlation analysis between various new, proposed metrics involving the
      HR, MR and LR fractions and the total reticulocyte count, with the latter
      indicative of stress erythropoiesis at higher total counts, revealed a highly
      significant correlation indicating these new metrics may be a valuable adjunct to
      the reticulocyte maturation index (RMI) and the immature reticulocyte fractions
      index (IRF) previously used in assessing erythropoietic activity in response to
      anemia.

PMID- 16284921
TI  - Population pharmacokinetic-pharmacodynamic modeling of subcutaneous and pulmonary
      insulin in rats.
AB  - PURPOSE: To develop a population pharmacokinetic-pharmacodynamic (PKPD) model for
      insulin in rats. METHODS: Rats were administered insulin either subcutaneously
      (s.c) (0.26,1.3,2.6 U/kg) or by pulmonary route (spray-instillation (s.i))
      (0.26,1.3,2.6,13,26 U/kg). Insulin (0.26,1.3,2.6 U/kg) combined with different
      combinations of hydroxy methyl amino propionic acid (HMAP: 5,10,16,25 mg/kg) was
      also administered by spray-instillation. Plasma insulin and glucose
      concentrations at pre-determined time points were measured. Population
      pharmacokinetic-pharmacodynamic modeling was performed using NONMEM. RESULTS:
      Insulin exhibited dose-disproportional PK across formulations and routes of
      administration. The kinetic model suggested monoexponential disposition with
      simultaneous first order (64%-dimeric form of insulin) - zero order (36%
      hexameric form of insulin) absorption. Maximum relative bioavailability (relative
      to s.c - 0.26 U/kg) of spray-instilled insulin was 46%. Addition of HMAP
      increased the relative bioavailability of insulin administered via spray
      instilled route by 40%. The insulin-glucose relationship was characterized using
      an indirect response model, wherein, insulin stimulation of glucose uptake into
      muscle cells was assumed. The basal zero order production rate of glucose (k(G,
      prod)) was estimated as 0.98 mg/dl/min. The SC50 was fixed at 80 mu U/ml based on
      literature reports and the S(max) was estimated to be 6. CONCLUSIONS: The
      proposed PKPD model satisfactorily describes insulin disposition and glucose
      concentrations across range of doses with and without HMAP.

PMID- 16284922
TI  - A comment on the application of drug tissue-plasma partition coefficients K(p) in
      eliminating organs to calculation of volume of distribution at steady state.

PMID- 16284923
TI  - Local intracerebral administration of Paclitaxel with the paclimer delivery
      system: toxicity study in a canine model.
AB  - INTRODUCTION: Paclitaxel, a microtubule binding agent with potent anti-glioma
      activity in vitro, exhibits poor penetrance to the CNS when delivered
      systemically. To minimize toxicity and reach therapeutic concentrations in the
      CNS, paclitaxel was previously incorporated into biodegradable microspheres
      (Paclimer), and the efficacy of Paclimer was determined in a rat model of
      malignant glioma. In this study we report the safety of intracranial Paclimer in
      a canine dose escalation toxicity study to prepare its translation into clinical
      scenarios. METHODS: Twelve normal beagle dogs underwent a right parieto-occipital
      craniectomy and were randomized to receive either Paclimer at 2-mg/kg (n=5),
      empty microspheres at 2-mg/kg (n=1), Paclimer at 20-mg/kg (n=5), or empty
      microspheres at 20-mg/kg (n=1). Post-operatively, dogs were observed daily for
      signs of neurotoxicity. Complete blood counts and plasma levels of paclitaxel
      were obtained weekly. CSF levels and MRI scans were obtained on days 14-120.
      Paclitaxel concentrations were quantified by LC-MS. RESULTS: Animals treated with
      20-mg/kg Paclimer had minimal paclitaxel levels in plasma (range 0-7.84 ng/ml)
      and CSF (range 0-1.16 ng/ml). Animals treated with 2 mg/kg Paclimer had
      undetectable levels of paclitaxel in plasma, CSF was not obtained to minimize
      animal suffering. All animals exhibited normal behavior and weight gain, and were
      alive post-operatively through the last day of the study (day 60-120) without
      signs of neurological toxicity. There was no evidence of systemic toxicity or
      myelosuppression. MR imaging was comparable between Paclimer animals and
      controls. Adverse effects included wound infections and a brain abscess, all of
      which responded to antibiotic therapy, and one ventriculomegaly due to
      communicating hydrocephalus. CONCLUSIONS: Paclimer-based delivery of paclitaxel
      is safe for intraparenchymal delivery at the tested doses in normal dogs.

PMID- 16284924
TI  - Pyrene mineralization capacity increases with compost maturity.
AB  - Experiments were conducted to determine the effects of composting or simple
      addition of compost to the mineralization of n-hexadecane, pyrene and
      benzo(a)pyrene in soil. Soil (contaminated or clean) was composted with maple
      leaves and alfalfa. Samples from different composting phases were spiked with
      radiolabeled and cold n-hexadecane, pyrene or benzo(a)pyrene, placed in aerated
      microcosms at different temperatures, and monitored for mineralization. It was
      determined that neither composting nor the addition of compost had any effect on
      n-alkane or benzo(a)pyrene mineralization. In contrast, the pyrene mineralization
      rate increased dramatically with the amount of time that soil had been composted.
      Highest pyrene mineralization rates and extents (more than 60% after 20 days)
      were obtained when pyrene was in contact with composted soil from the curing
      stage. Neither thermophiles (55 degrees C) nor fungi were responsible for pyrene
      mineralization.

PMID- 16284925
TI  - Phylogenetic analysis and biochemical characterization of a thermostable
      dihydropyrimidinase from alkaliphilic Bacillus sp. TS-23.
AB  - Two degenerate primers established from the alignment of highly conserved amino
      acid sequences of bacterial dihydropyrimidinases (DHPs) were used to amplify a
      330-bp gene fragment from the genomic DNA of Bacillus sp. TS-23 and the amplified
      DNA was successfully used as a probe to clone a dhp gene from the strain. The
      open reading frame of the gene consisted of 1422 bp and was deduced to contain
      472 amino acids with a molecular mass of 52 kDa. The deduced amino acid sequence
      exhibited greater than 45% identity with that of prokaryotic D-hydantoinases and
      eukaryotic DHPs. Phylogenetic analysis showed that Bacillus sp. TS-23 DHP is
      grouped together with Bacillus stearothermophilus D-hydantoinase and related to
      dihydroorotases and allantoinases from various organisms. His6-tagged DHP was
      over-expressed in Escherichia coli and purified by immobilized metal affinity
      chromatography to a specific activity of 3.46 U mg(-1) protein. The optimal pH
      and temperature for the purified enzyme were 8.0 and 60 degrees C, respectively.
      The half-life of His6-tagged DHP was 25 days at 50 degrees C. The enzyme activity
      was stimulated by Co2+ and Mn2+ ions. His6-tagged DHP was most active toward
      dihydrouracil followed by hydantoin derivatives. The catalytic efficiencies
      (kcat/Km) of the enzyme for dihydrouracil and hydantoin were 2.58 and 0.61 s(-1)
      mM(-1), respectively.

PMID- 16284926
TI  - Cellular lipid fatty acid pattern heterogeneity between reference and recent food
      isolates of Listeria monocytogenes as a response to cold stress.
AB  - Cells of four reference strains (Scott A, LO 28, CNL 895807 and ATCC 19115) and
      of five recent food isolates (A00M011, A00M018, A00M087, A00M092 and A00M123) of
      Listeria monocytogenes were grown until late exponential phase in Brain Heart
      Broth at two different temperatures (37 degrees C and 4 degrees C). Our results
      show that significant differences exist between the cellular lipid fatty acid
      profile of reference and recent food isolates. Like the reference strains, and in
      keeping with previous reports on the cellular lipid fatty acid profile of L.
      monocytogenes, the recent food isolates were characterised by the presence of
      ai15:0, i15:0 and ai17:0. In addition, the fatty acid ai13:0 was observed in all
      of the recent food isolates grown at 4 degrees C, whereas only two reference
      strains, Scott A and LO 28, showed ai13:0 in their cellular lipid fatty acid
      profile at 4 degrees C. When grown at 4 degrees C, the recent food isolates
      showed a mean aiC15/aiC17 ratio of 66, while reference strains were characterised
      by significantly lower ratios, ranging between 4.3 (ATCC 19115) and 28.9 (Scott
      A). These results showed that all of the recent food isolates, Scott A and LO28
      strains use chain length and anteiso-branching (ai15:0) as their major response
      to cold temperature adaptation. However, the cold adaptation response of
      reference strains CNL 895807 and ATCC 19115 appears to be different.

PMID- 16284927
TI  - Conditions affecting cell surface properties of human intestinal bifidobacteria.
AB  - The cell surface properties of human intestinal bifidobacteria have been
      characterized for 30 strains isolated from a fecal sample. Strain identification
      to the species level was obtained by restriction analysis of the amplified 16S
      rRNA gene and confirmed by DNA/DNA reassociation experiments. The isolates were
      grouped in four genetically homogeneous clusters whose members belonged to
      Bifidobacterium bifidum, Bifidobacterium adolescentis, Bifidobacterium longum and
      Bifidobacterium pseudocatenulatum species. Cell surface properties of
      Bifidobacterium strains were evaluated by determining the level of
      hydrophobicity, adhesion to hydrocarbons and contact angle measurements, and
      their autoaggregation ability. The results showed high and homogeneous level of
      hydrophobicity in all tested strains when contact angle measurements values were
      considered. On the contrary, autoaggregation assays and bacterial adhesion to
      hydrocarbons detected interesting differences in cell surface properties among
      the tested Bifidobacterium strains. The highest levels of autoaggregation,
      detected in B. bifidum and B. adolescentis strains, were strictly dependent on
      the pH of the medium. Moreover, protease treatment experiments suggested that
      proteins had a key role in the autoaggregating ability of B. bifidum and B.
      adolescentis strains.

PMID- 16284928
TI  - Biosynthesis of glycoproteins in the human pathogenic fungus Sporothrix
      schenckii: synthesis of dolichol phosphate mannose and mannoproteins by membrane
      bound and solubilized mannosyl transferases.
AB  - A membrane fraction obtained from the filamentous form of Sporothrix schenckii
      was able to transfer mannose from GDP-Mannose into dolichol phosphate mannose and
      from this inTermediate into mannoproteins in coupled reactions catalyzed by
      dolichol phosphate mannose synthase and protein mannosyl transferase(s),
      respectively. Although the transfer reaction depended on exogenous dolichol
      monophosphate, membranes failed to use exogenous dolichol phosphate mannose for
      protein mannosylation to a substantial extent. Over 95% of the sugar was
      transferred to proteins via dolichol phosphate mannose and the reaction was
      stimulated several fold by Mg2+ and Mn2+. Incubation of membranes with detergents
      such as Brij 35 and Lubrol PX released soluble fractions that transferred the
      sugar from GDP-Mannose mostly into mannoproteins, which were separated by
      affinity chromatography on Concanavilin A-Sepharose 4B into lectin-reacting and
      non-reacting fractions. All proteins mannosylated in vitro eluted with the lectin
      reacting proteins and analytical electrophoresis of this fraction revealed the
      presence of at least nine putative mannoproteins with molecular masses in the
      range of 26-112 kDa. The experimental approach described here can be used to
      identify and isolate specific glycoproteins mannosylated in vitro in studies of O
      glycosylation.

PMID- 16284929
TI  - Taxonomy and phylogeny of Synchaetomella lunatospora, a new genus and species of
      synnematous fungi from Southeast Asia.
AB  - The anamorphic fungus Synchaetomella lunatospora gen. et sp. nov. is described
      from a culture isolated from leaf litter in Singapore. The genus is characterized
      by the production of synnematous conidiomata with brown stipes, phialidic
      conidiogenesis with terminal and acropleurogenous conidiogenous cells, and
      falcate, 1-septate conidia, aggregating in white, mucilaginous heads. Its
      phylogenetic relationships, inferred from the partial nuclear small ribosomal
      subunit (18S) sequence, are with the coelomycetous genera Sphaerographium,
      Chaetomella, and Hainesia. However, the order and family affinities of this group
      are unclear.

PMID- 16284930
TI  - Kuraishia molischiana sp. nov., the teleomorph of Candida molischiana.
AB  - Thirty-two strains, many of them isolated from wood-associated habitats, and
      designated as Kuraishia (Pichia) capsulata and Candida molischiana according to
      their phenotype, exhibited two types of HaeIII restriction fragment patterns of
      their small subunit rDNA with the neighboring ITS. One fragment pattern
      corresponded to that of the type strain of K. capsulata, whereas the other
      pattern was unique to the typestrain of C. molischiana. Sequencing of the D1/D2
      domain of the large subunit rDNA confirmed that the different HaeIII restriction
      fragment patterns of small subunit rDNA with the neighboring ITS reliably
      distinguished K. capsulata from C. molischiana. Ascospore formation was observed
      in several C. molischiana strains and K. molischiana (type strain: NCAIM Y.01725,
      CBS 9993) is proposed as the teleomorphic state of Candida molischiana.

PMID- 16284931
TI  - Differences in mitochondrial genome organization of Cryptococcus neoformans
      strains.
AB  - The organization of the mitochondrial genomes in two strains belonging in
      different varieties of Cryptococcus neoformans was analysed. Physical maps of the
      mtDNA of the IFM5844 (var. neoformans) and IFO410 (var. grubii) strains were
      constructed by using EcoRI and EcoRV restriction enzymes; functional maps were
      constructed by hybridization, cloning and sequencing. Most of the genes important
      in the mitochondrial function (ND1, ND2, ND3, ND4, ND4L, ND5, ND6, ATP6, ATP9,
      COX1, COX2 and COB) and protein synthesis (SsrRNA and LsrRNA) were localized. We
      did not find any differences between the strains in the order of these genes.
      However, they differed significantly in the sizes of the mtDNAs: 32.6 kb for
      IFM5844, and 24.1 kb for IFO410. This can be attributed to two large regions of
      the mtDNA. In these regions, differences were found in the numbers of introns in
      COX1 (no intron in var. grubii, 5 introns in var. neoformans), COB (1 intron in
      var. grubii, 2 introns in var. neoformans), LsrRNA (no intron in var. grubii, 2
      introns in var. neoformans), and ND5 (no intron in var. grubii, 1 intron in var.
      neoformans) genes. In several introns of the COB and COX1 genes LAGLIDADG motifs
      were found. Differences were also observed in the nucleotide sequences of some
      genes and in the sizes and sequences of intergenic regions. The nucleotide
      sequences of the genes of the IFM and IFO strains were compared with those of the
      H-99 and JEC 21 strains from the database. Surprisingly high similarities were
      found between the strains belonging in var. grubii (IFO 410 and H-99) and var.
      neoformans (IFM 5844 and JEC 21).

PMID- 16284932
TI  - Morphological, biochemical and molecular approaches for comparing typical and
      atypical Paracoccidioides brasiliensis strains.
AB  - We evaluated the morphology of typical and atypical Paracoccidioides brasiliensis
      strains and the expression of its 43 kDa glycoprotein (GP43). Strains of P.
      brasiliensis preserved under mineral oil for long periods of time presented
      different morphological patterns on peptone, yeast-extract and glucose (PYG)
      agar. The intravenous inoculation in BALB/c mice confirmed that a strain bearing
      morphological alterations was non-virulent. In contrast, another strain also
      maintained under mineral oil but which did not exhibit such morphological
      dysfunction was as virulent as the well characterized Pb 339 and Pb 18 strains.
      The expression of the main antigen expressed by P. brasiliensis, GP43, was
      assessed in culture filtrates by western immunoblots. Typical and atypical
      strains were capable of secreting the glycoprotein, except strain Pb IOC 1059.
      The identity of the atypical strains was confirmed by PCR using specific primers
      for gp43, though the single PCR-fragment varied in size for the atypical strains.
      The PCR fragments from an atypical strain, Pb IOC 1210, and the typical Pb 339
      and Pb IOC 3698 strains were sequenced and blasted to the gp43 gene from the Pb
      18 strain (GenBank AY005429). These results ensured the identity of the atypical
      strains as P. brasiliensis, and suggested a relationship between the alteration
      of morphological differentiation and the virulence factor following storage under
      mineral oil.

PMID- 16284933
TI  - Isolation and sequencing of a new glucoamylase gene from an Aspergillus niger
      aggregate strain (DSM 823) molecularly classified as Aspergillus tubingensis.
AB  - Based on morphological characteristics the taxa included in the Aspergillus
      aggregate can hardly be differentiated. For that reason the phylogeny of this
      genus was revised several times as different criteria, from morphological to
      later molecular, were used. We found, comparing nucleotide sequences of the ITS
      region, that the strain Aspergillus niger (DSM 823) which is claimed to be
      identical to the strains ATCC 10577, IMI 027809, NCTC 7193 and NRRL 2322 can be
      molecularly classified as Aspergillus tubingensis, exhibiting 100% identity with
      the A. tubingensis CBS strains 643.92 and 127.49. We amplified, cloned and
      sequenced a new glucoamylase gene (glaA) from this strain of A. tubingensis (A.
      niger DSM 823) using primers derived from A. niger glucoamylase G1. The amplified
      cDNA fragment of 2013 bp contained an open reading frame encoding 648 amino acid
      residues. The calculated molecular mass of the glucoamylase, deduced from the
      amino acid sequence, was 68 kDa. The nucleotide sequence of glaA showed 99%
      similarity with glucoamylases from Aspergillus kawachii and Aspergillus
      shirousami, whereas the similarity with the glucoamylase G1 from A. niger was 92%

PMID- 16284937
TI  - Adeno-associated vector mediated gene transfer of transforming growth factor
      beta1 to normal and osteoarthritic human chondrocytes stimulates cartilage
      anabolism.
AB  - The objective of the present study was to investigate whether cartilage anabolism
      in human primary osteoarthritic chondrocytes could be improved by adeno
      associated virus (AAV) vector-mediated gene transduction of transforming growth
      factor TGF-beta1 (TGF-beta1). A bi-cistronic AAV-TGF-beta1-IRES-eGFP (AAV-TGF
      beta1) vector was generated and used for transduction of a normal human articular
      chondrocyte cell line (tsT/AC62) and primary human osteoarthritic articular
      chondrocytes harvested from 8 patients receiving total knee joint arthroplasty.
      Transduction efficiency was detected by fluorescent microscopy for gene
      expression of enhanced green fluorescent protein (eGFP). TGF-beta1 synthesis was
      determined by ELISA. To assess the influence of TGF-beta1 gene therapy on
      chondrocyte cartilage metabolism, mRNA expressions of type II collagen, aggrecan,
      and matrix metalloproteinase 3 (MMP-3) were determined by quantitative real-time
      PCR. AAV-TGF-beta1 transduction resulted in increased synthesis of TGF-beta1 in
      both osteoarthritic chondrocytes and the normal articular chondrocyte cell line.
      The expression levels of the transduced genes were correlated to "multiplicity of
      infection" (MOI) and post-infectious time. In both osteoarthritic chondrocytes
      and the normal articular chondrocyte cell line, AAV-TGF-beta1 treatment increased
      mRNA expression of both type II collagen and aggrecan, but decreased MMP-3 mRNA
      expression. Osteoarthritic chondrocytes and the normal articular chondrocyte cell
      line could be transduced with equal efficiencies. In conclusion, it was
      demonstrated that AAV-TGF-beta1 gene transfer stimulates cartilage anabolism and
      decreases expression of enzymes responsible for cartilage degradation in human
      osteoarthritic chondrocytes. The results indicate that the AAV vector is an
      efficient mediator of growth factors to human articular chondrocytes, and that it
      might be useful in future chondrocyte gene therapy.

PMID- 16284934
TI  - Resistance to antimicrobial agents in lactobacilli isolated from caper
      fermentations.
AB  - A collection of lactobacilli comprising species of Lactobacillus plantarum (43
      isolates), Lactobacillus brevis (9 isolates) and Lactobacillus fermentum (6
      isolates) obtained from spontaneous fermentations of capers (the fruits of
      Capparis spinosa) were investigated for resistance to antimicrobial agents. All
      isolates were resistant to vancomycin and teicoplanin (MIC > 16 microg/ml).
      Resistance to ciprofloxacin (MIC > 2 microg/ml) was detected in all isolates of
      L. brevis and L. fermentum as well as in most isolates of L. plantarum, whilst
      resistance to levofloxacin showed a much lower incidence. Among L. plantarum and
      L. brevis isolates, low levels of resistance to tetracycline and/or
      nitrofurantoin were detected. Higher resistance levels were also detected in some
      isolates. Resistance to penicillin and rifampicin were also detected among L.
      plantarum isolates. All isolates were sensitive to ampicillin, erythromycin,
      chloramphenicol, gentamicin, streptomycin, and quinupristin/dalfopristin.

PMID- 16284938
TI  - The role of mass spectrometry in plant systems biology.
AB  - Large-scale analyses of proteins and metabolites are intimately bound to
      advancements in MS technologies. The aim of these non-targeted "omic"
      technologies is to extend our understanding beyond the analysis of only parts of
      the system. Here, metabolomics and proteomics emerged in parallel with the
      development of novel mass analyzers and hyphenated techniques such as gas
      chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) and
      multidimensional liquid chromatography coupled to mass spectrometry (LC-MS). The
      analysis of (i) proteins (ii) phosphoproteins, and (iii) metabolites is discussed
      in the context of plant physiology and environment and with a focus on novel
      method developments. Recently published studies measuring dynamic (quantitative)
      behavior at these levels are summarized; for these works, the completely
      sequenced plants Arabidopsis thaliana and Oryza sativa (rice) have been the
      primary models of choice. Particular emphasis is given to key physiological
      processes such as metabolism, development, stress, and defense. Moreover,
      attempts to combine spatial, tissue-specific resolution with systematic profiling
      are described. Finally, we summarize the initial steps to characterize the
      molecular plant phenotype as a corollary of environment and genotype.

PMID- 16284939
TI  - Automated protein identification by tandem mass spectrometry: issues and
      strategies.
AB  - Protein identification by tandem mass spectrometry (MS/MS) is key to most
      proteomics projects and has been widely explored in bioinformatics research.
      Obtaining good and trustful identification results has important implications for
      biological and clinical work. Although well matured, automated software
      identification of proteins from MS/MS data still faces a number of obstacles due
      to the complexity of the proteome or procedural issues of mass spectrometry data
      acquisition. Expected or unexpected modifications of the peptide sequences,
      polymorphisms, errors in databases, missed or non-specific cleavages, unusual
      fragmentation patterns, and single MS/MS spectra of multiple peptides of the same
      m/z are so many pitfalls for identification algorithms. A lot of research work
      has been carried out in recent years that yielded new strategies to handle a
      number of these issues. Multiple MS/MS identification algorithms are now
      available or have been theoretically described. The difficulty resides in
      choosing the most adapted method for each type of spectra being identified. This
      review presents an overview of the state-of-the-art bioinformatics approaches to
      the identification of proteins by MS/MS to help the reader doing the spade work
      of finding the right tools among the many possibilities offered.

PMID- 16284940
TI  - Array-based comparative genomic hybridization analysis of recurrent chromosome
      15q rearrangements.
AB  - Genomic rearrangements of chromosome 15q11-q13 cause diverse phenotypes including
      autism, Prader-Willi syndrome (PWS), and Angelman syndrome (AS). This region is
      subject to genomic imprinting and characterized by complex combinations of low
      copy repeat elements. Prader-Willi and Angelman syndrome are caused primarily by
      15q11-13 deletions of paternal and maternal origin, respectively. Autism is seen
      with maternal, but not paternal, interstitial duplications. Isodicentric 15q,
      most often of maternal origin, is associated with a complex phenotype often
      including autistic features. Limitations of conventional cytogenetic tests
      preclude a detailed analysis in most patients with 15q rearrangements. We have
      developed a microarray for comparative genomic hybridization utilizing 106
      genomic clones from chromosome 15q to characterize this region. The array
      accurately localized all breakpoints associated with gains or losses on 15q. The
      results confirmed the location of the common breakpoints associated with
      interstitial deletions and duplications. The majority of idic(15q) chromosomes
      are comprised of symmetrical arms with four copies of the breakpoint 1 to
      breakpoint 5 region. Patients with less common breakpoints that are not
      distinguished by routine cytogenetic methods were more accurately characterized
      by array analysis. This microarray provides a detailed characterization for
      chromosomal abnormalities involving 15q11-q14 and is useful for more precise
      genotype-phenotype correlations for autism, PWS, AS, and idic(15) syndrome.

PMID- 16284941
TI  - Analysis of Meox-2 mutant mice reveals a novel postfusion-based cleft palate.
AB  - Cleft palate represents a common human congential disease involving defects in
      the development of the secondary palate. Major steps in mammalian palatogenesis
      include vertical growth, elevation, and fusion of the palate shelves. Our current
      study with the homeobox gene Meox-2 during mouse secondary palate development
      reveals a novel postfusion-based mechanism for cleft palate. Meox-1 and Meox-2
      are two functionally related homeobox genes playing important roles in
      somitogenesis and limb muscle differentiation. We found that the expression of
      Meox-2, not Meox-1, marks the specification of early mouse palatal mesenchymal
      cells in the maxillary processes at embryonic day 11.5 (E11.5). From E12.5 to
      E15.5, the expression of Meox-2 occupies only the posterior part of the palate,
      providing an early molecular marker for the anterior-posterior polarity in mouse
      secondary palate formation. A total of 35.3% of Meox-2-/- (n = 17) and 25.5% of
      Meox-2+/- (n = 55) mouse embryos display a cleft palate phenotype at E15.5,
      indicating that the reduction of Meox-2 function is associated with
      susceptibility to cleft palate. Unlike previously reported clefts, none of the
      clefts found in Meox-2 mutants contain any epithelial sheets in the medial edge
      areas, and detailed examination revealed that the clefts resulted from the
      breakdown of newly fused palates. This article is the first report of a gene
      required to maintain adherence of the palatal shelves after fusion.

PMID- 16284942
TI  - Expression and functional analysis of Tgif during mouse midline development.
AB  - The Tgif gene encodes a homeodomain protein that functions as a transforming
      growth factor beta (TGF-beta) repressor by binding to Smad2. Mutations in the
      TGIF gene are associated with human holoprosencephaly, a common birth defect
      caused by the failure of anterior ventral midline formation. However, Smad2
      mediated TGF-beta signaling in the axial mesendoderm has been demonstrated to be
      essential for ventral midline formation, and loss of a Smad2 antagonist should in
      principle promote rather than inhibit ventral midline formation. This suggests a
      more complex mechanism for the function of TGIF in controlling ventral midline
      formation. To explore the role of TGIF in ventral forebrain formation and
      patterning, we investigated Tgif expression and function during mouse development
      by in situ hybridization and gene targeting. We found that Tgif is highly
      expressed in the anterior neural plate, consistent with the proposed neural
      differentiation model in which TGF-beta suppression is required for normal neural
      differentiation. This result suggests a possible role for Tgif in anterior neural
      differentiation and patterning. However, targeted disruption of the Tgif gene
      during mouse development does not cause any detectable defects in development and
      growth. Both histological examination and gene expression analysis showed that
      Tgif-/- embryos have a normal ventral specification in the central nervous
      system, including the forebrain region. One interpretation of these results is
      that the loss of TGIF function is compensated by other TGF-beta antagonists such
      as c-Ski and SnoN during vertebrate anterior neural development.

PMID- 16284943
TI  - Comparative anatomy of the cheek muscles within the Centromochlinae subfamily
      (Ostariophysi, Siluriformes, Auchenipteridae).
AB  - Glanidium melanopterum Miranda Ribeiro, a typical representative of the subfamily
      Centromochlinae (Siluriformes: Auchenipteridae), is herein described myologically
      and compared to other representative species within the group, Glanidium
      ribeiroi, G. leopardum, Tatia neivai, T. intermedia, T. creutzbergi,
      Centromochlus heckelii, and C. existimatus. The structure of seven pairs of
      striated cephalic muscles was compared anatomically: adductor mandibulae, levator
      arcus palatini, dilatator operculi, adductor arcus palatini, extensor tentaculi,
      retractor tentaculi, and levator operculi. We observed broad adductor mandibulae
      muscles in both Glanidium and Tatia, catfishes with depressed heads and smaller
      eyes. Similarities between muscles were observed: the presence of a large
      aponeurotic insertion for the levator arcus palatini muscle; an adductor arcus
      palatini muscle whose origin spread over the orbitosphenoid, pterosphenoid, and
      parasphenoid; and the extensor tentaculi muscle broadly attached to the
      autopalatine. There is no retractor tentaculi muscle in either the Glanidium or
      Tatia species. On the other hand, in Centromochlus, with forms having large eyes
      and the tallest head, the adductor mandibulae muscles are slim; there is a thin
      aponeurotic or muscular insertion for the levator arcus palatini muscle; the
      adductor arcus palatini muscle originates from a single osseous process, forming
      a keel on the parasphenoid; the extensor tentaculi muscle is loosely attached to
      the autopalatine, permitting exclusive rotating and sliding movements between
      this bone and the maxillary. The retractor tentaculi muscle is connected to the
      maxilla through a single tendon, so that both extensor and retractor tentaculi
      muscles contribute to a wide array of movements of the maxillary barbels. A
      discussion on the differences in autopalatine-maxillary movements among the
      analyzed groups is given.

PMID- 16284944
TI  - External sense organs in freshwater oligochaetes (Annelida, Clitellata) revealed
      by scanning electron microscopy.
AB  - Freshwater oligochaetes have at least two kinds of external sense organs:
      multiciliate organs of short cilia (also present in earthworms) and sense organs
      with one to three long cilia (unknown in earthworms and possibly acting as
      rheoreceptors). Ciliate sense organs of freshwater oligochaetes are distributed
      over their entire body surface, including the clitellum. They are scattered on
      the prostomium and pigidium and are arranged into a transversal chaetal row and
      dispersed or forming a few other discrete transversal rows on chaetal segments.
      Three species display very prominent sense organs (sensory buds in
      Protuberodrilus tourenqui and papillae in Ophidonais serpentina and Spirosperma
      velutinus). The number of cilia per organ at the prostomium of freshwater
      families appears to be fewer than that of terrestrial ones. It is suggested that
      the total number of cilia at the prostomium of the freshwater species could be
      related to their habitat, evolving from an epibenthic to an endobenthic way of
      life.

PMID- 16284945
TI  - Diabetes mellitus and cancer risk in a population-based case-control study among
      men from Montreal, Canada.
AB  - Diabetics may have a higher risk of cancer, notably liver and pancreatic cancers.
      Evidence about other cancer types remains sparse. The authors examined potential
      associations between diabetes and several types of cancer in a large multicancer
      case-control project carried out in Montreal, Canada, in the 1980s. This report,
      based on 3,107 male cancer cases and 509 population controls, uses information on
      diabetes and several covariates collected by interview. Adjusted odds ratios
      (ORs) and 95% confidence intervals (CI) were estimated for the associations
      between diabetes and each of 12 cancer types. Risks of pancreatic and liver
      cancers were increased among diabetics: adjusted ORs were 2.1 (95% CI: 1.0, 4.3)
      for pancreatic and 3.1 (95% CI: 1.1, 8.8) for liver cancer. The increased risk of
      pancreatic cancer was completely restricted to those with recent onset of
      diabetes; this was likely a manifestation of reverse causality. Conversely, the
      increased risk of liver cancer was independent of the interval between diabetes
      and cancer diagnoses. No associations were observed with melanoma, non-Hodgkin's
      lymphoma, cancers of the esophagus, stomach, colon, rectum, lung, prostate,
      bladder and kidney. In conclusion, diabetes was associated with an increased risk
      of liver cancer among men, but with no other cancer type including pancreatic
      cancer.

PMID- 16284947
TI  - Long-term risk of invasive cervical cancer after treatment of squamous cervical
      intraepithelial neoplasia.
AB  - Invasive cancer of the cervix after treatment for cervical intraepithelial
      neoplasia (CIN) is becoming more important, as screening reduces the incidence of
      invasive disease. The rate of invasive cervical or vaginal cancer following
      treatment for CIN in UK remains elevated for at least 8 years. The aim of our
      study was to determine from international data how long this rate remains
      elevated and whether the rate of invasive disease reflects the rate of
      posttreatment CIN. The aim was to determine why the rate of invasive disease does
      not fall. A search of Medline and a secondary search of cited references
      identified 1,848 articles referring to the success rate of the treatment of CIN.
      Only 26 cohorts from 25 articles met all the inclusion criteria. The policy in
      these was to perform at least annual smears. After the first year following
      treatment for CIN, the rate of invasive disease remained about 56 per 100,000
      woman years until at least 20 years after treatment. This rate is approximately
      2.8 times greater than expected. In contrast, the risk of posttreatment CIN
      declined steadily with time to about 190 per 100,000 women in the 10th year.
      Although the posttreatment rate of CIN falls with time, the rate of invasive
      disease remains static. It seems likely that this is due to diminishing
      compliance with follow-up. Women should be encouraged to persevere with annual
      smears for at least 10 years after their treatment as this may offer them the
      best chance of detecting recurrence at a treatable stage.

PMID- 16284946
TI  - Human attachment security is mediated by the amygdala: evidence from combined
      fMRI and psychophysiological measures.
AB  - The neural basis of human attachment security remains unexamined. Using event
      related functional magnetic resonance imaging (fMRI) and simultaneous recordings
      of skin conductance levels, we measured neural and autonomic responses in healthy
      adult individuals during a semantic conceptual priming task measuring human
      attachment security "by proxy". Performance during a stress but not a neutral
      prime condition was associated with response in bilateral amygdalae. Furthermore,
      levels of activity within bilateral amygdalae were highly positively correlated
      with attachment insecurity and autonomic response during the stress prime
      condition. We thereby demonstrate a key role of the amygdala in mediating
      autonomic activity associated with human attachment insecurity.

PMID- 16284948
TI  - Rearrangement of the COL12A1 and COL4A5 genes in subungual exostosis: molecular
      cytogenetic delineation of the tumor-specific translocation t(X;6)(q13-14;q22).
AB  - Subungual exostosis is a benign bone- and cartilage-producing tumor occurring in
      the hands and feet of children and young adults. The recent identification of a
      recurrent chromosomal translocation t(X;6)(q24-q26;q15-21) in short-term-cultured
      tumor cells strongly suggests that subungual exostosis is a neoplastic lesion
      caused by rearrangement of genes in the two breakpoints. To identify the genes
      that are critical for neoplastic transformation, we have studied five subungual
      exostoses by interphase or metaphase FISH. The results of these analyses
      demonstrated a clustering of the breakpoints to the regions harboring the
      collagen genes COL12A1 and COL4A5 in chromosome bands 6q13-14 and Xq22,
      respectively. Furthermore, in all but one case, these two genes were shown to
      colocalize on the derivative chromosomes X and 6, strongly suggesting that at
      least one of them is consistently involved in the formation of a chimeric fusion
      gene or in the exchange of regulatory sequences. Because collagen molecules are
      important for tissue remodeling during physiologic growth and differentiation,
      both COL12A1 and COL4A5 constitute good candidate target genes in the
      pathogenesis of subungual exostosis. Further investigations on the transcript
      level are required to elucidate the functional outcome of the t(X;6)
      translocation in subungual exostoses.

PMID- 16284949
TI  - Essential contribution of a chemokine, CCL3, and its receptor, CCR1, to
      hepatocellular carcinoma progression.
AB  - We previously observed that a chemokine, macrophage inflammatory protein-1
      alpha/CCL3, and its receptor, CCR1, were aberrantly expressed in human
      hepatocellular carcinoma (HCC) tissues. Here, we show that CCL3 and CCR1 are also
      expressed in 2 different models of this cancer; N-nitrosodiethylamine (DEN)
      induced HCC and HCC induced by hepatitis B virus surface (HBs) antigen-primed
      splenocyte transfer to myelo-ablated syngeneic HBs antigen transgenic mice. At 10
      months after DEN treatment, foci number and sizes were remarkably reduced in CCR1
      and CCL3-deficient mice, compared with those of wild-type (WT) mice, although
      tumor incidence were marginally, but significantly, higher in CCR1- and CCL3
      deficient mice than in WT mice. Of note is that tumor angiogenesis was also
      markedly diminished in CCL3- and CCR1-deficient mice, with a concomitant
      reduction in the number of intratumoral Kupffer cells, a rich source of growth
      factors and matrix metalloproteinases (MMPs). Among growth factors and MMPs that
      we examined, only MMP9 and MMP13 gene expression was augmented progressively in
      liver of WT mice after DEN treatment. Moreover, MMP9, but not MMP13, gene
      expression was attenuated in CCR1- and CCL3-deficient mice, compared with that of
      WT mice. Furthermore, MMP9 was expressed mainly by mononuclear cells but not
      hepatoma cells, and MMP9-expressing cell numbers were decreased in CCR1- or CCL3
      deficient mice, compared with WT mice. These observations suggest the
      contribution of the CCR1-CCL3 axis to HCC progression.

PMID- 16284950
TI  - Inhibition of nuclear factor kappab activity by genistein is mediated via Notch-1
      signaling pathway in pancreatic cancer cells.
AB  - Pancreatic cancer remains the fourth most common cause of cancer related death in
      the United States. Therefore, novel strategies for the prevention and treatment
      are urgently needed. Genistein is a prominent isoflavonoid found in soy products
      and has been proposed to be responsible for lowering the rate of pancreatic
      cancer in Asians. However, the molecular mechanism(s) by which genistein elicits
      its effects on pancreatic cancer cells has not been fully elucidated. We have
      previously shown that genistein induces apoptosis and inhibits the activation of
      nuclear factor kappaB (NF-kappaB) pathway. Moreover, Notch signaling is known to
      play a critical role in maintaining the balance between cell proliferation,
      differentiation and apoptosis, and thereby may contribute to the development of
      pancreatic cancer. Hence, in our study, we investigated whether there is any
      cross talk between Notch and NF-kappaB during genistein-induced apoptosis in BxPC
      3 pancreatic cancer cells. We used multiple cellular and molecular approaches
      such as MTT assay, apoptosis assay, gene transfection, Western blotting and EMSA
      for measuring DNA binding activity of NF-kappaB. We found that genistein inhibits
      cell growth and induces apoptotic processes in BxPC-3 pancreatic cancer cells.
      This was partly due to inhibition of Notch-1 activity. BxPC-3 cells transfected
      with Notch-1 cDNA showed induction of NF-kappaB activity, and this was inhibited
      by genistein treatment. From these results, we conclude that the inhibition of
      Notch-1 and NF-kappaB activity and their cross talk provides a novel mechanism by
      which genistein inhibits cell growth and induces apoptotic processes in
      pancreatic cancer cells.

PMID- 16284951
TI  - Reconstruction of foot defects with free lateral arm fasciocutaneous flaps:
      analysis of fifty patients.
AB  - In this article, long-term outcomes of foot reconstruction with free lateral arm
      fasciocutaneous flaps were retrospectively analyzed in 50 patients. The patients,
      38 men and 12 women, ranged in age from 7-73 years (mean, 43.5 years).
      Indications for surgery included trauma (32 patients), diabetes mellitus (7
      patients), burns (7 patients), chronic ulcers (3 patients), and tumor (1
      patient). The locations of defects were the dorsum (n=21), ankle (n=12), medial
      (n=6), lateral (n=6), posterior heel (n=2), and distal sole (n=3) Concomitant
      bone injury occurred in 5 cases, and the weight-bearing surface of the foot was
      involved in 5 patients. Defects ranged in size from 27-76 cm(2) (mean, 36.4
      cm(2)). Successful reconstructions were accomplished in 46 cases (92%). Flap
      complications included total flap loss and below-knee amputation (1 patient) and
      partial flap loss (3 patients); 75% (3/4) of these cases had diabetes as a
      comorbid factor, and 25% (1/4) had a concomitant bone injury. Six patients with
      dorsum defects required debulking of the flap (11.1%). None of the patients
      required modified shoes. In the majority of cases, flaps provided stable coverage
      and a gain in protective deep-pressure sensation. In long-term follow-up (up to 4
      years), patients regained their ambulation, free of pain. Even in weight-bearing
      areas, none of the cases experienced ulceration or skin breakdown. Free lateral
      arm flaps provided excellent durability, with solid bony union and successful
      restoration of the contour of the foot in moderate-sized foot defects.

PMID- 16284953
TI  - Are mechanical microvascular anastomoses easier to learn than suture anastomoses?
AB  - Sutured anastomoses of small vessels are considered difficult to learn.
      Mechanical anastomosis systems allow a more rapidly performed anastomosis. In
      order to compare the process of learning to perform sutured and mechanical
      microvascular anastomoses, two surgeons, with limited microvascular experience,
      performed 30 aortic and 30 femoral vein anastomoses in 30 Wistar rats. The
      methods compared were conventional suture, vascular closure system (VCS) and
      microvascular anastomatic coupler system (MAC). There were no inter-surgeon
      differences regarding patency or time to perform anastomoses. The average time to
      perform a suture anastomosis was 39 min (patency 80%). Anastomoses with the VCS
      system took 24 min (patency 25%), whereas the MAC couplers took 13 min to perform
      (patency 95%). There was a significant learning effect with sutures, but no
      obvious reduction in time to perform MAC coupler or VCS clip anastomoses was
      seen. MAC couplers were easiest to use, and allowed us to perform rapid
      anastomoses with high patency.

PMID- 16284952
TI  - Inhibition of iNOS attenuates skeletal muscle reperfusion injury in extracellular
      superoxide dismutase knockout mice.
AB  - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are closely
      involved in the mechanism of skeletal muscle ischemia/reperfusion (I/R) injury.
      This study was designed to determine the effects of inducible nitric oxide
      synthase (iNOS) inhibitor 1400 W on the reperfused cremaster muscle in
      extracellular super-oxide dismutase knockout (EC-SOD(-/-)) mice. The muscle was
      exposed to 4.5 h of ischemia, followed by 90 min of reperfusion. Mice received
      either 3 mg/kg of 1400 W or the same amount of phosphate-buffered saline (PBS, as
      a control) subcutaneously at 10 min before the start of reperfusion. 1400 W
      treatment markedly improved the recovery speed of vessel diameter and blood flow
      in the reperfused cremaster muscle of EC-SOD(-/-) mice compared to controls.
      Histological examination showed reduced edema in the interstitial space and
      muscle fiber, and reduced density of nitrotyrosine (a marker of total peroxi
      nitrate (ONOO(-)) level) in 1400 W-treated muscles compared to controls. Our
      results suggest that iNOS and ONOO(-) products are involved in skeletal muscle
      I/R injury. Reduced I/R injury by using selective inhibition of iNOS perhaps
      works by limiting cytotoxic ONOO(-) generation, a reaction product of nitric
      oxide (NO) and super-oxide anion (O(2) (-)). Thus, inhibition of iNOS appears to
      be a treatment strategy for reducing clinical I/R injury.

PMID- 16284954
TI  - A prospective study of breast size and premenopausal breast cancer incidence.
AB  - Studies of the association between breast size, as a proxy for mammary gland
      mass, and breast cancer risk have given equivocal results. Most have been case
      control studies with limited statistical power. We conducted a prospective
      analysis of the relation between breast size as measured by self-reported bra cup
      size and breast cancer risk among premenopausal women enrolled in the Nurses'
      Health Study II. Bra cup size at age 20 was assessed among 89,268 premenopausal
      women aged 29-47 in 1993. Subsequent incident cases of invasive breast cancer
      were assessed until 2001. Hazard ratios (HRs) and 95% confidence intervals (CIs)
      were calculated with a Cox proportional hazards model adjusting for potential
      confounders and risk factors for breast cancer. During 622,732 person-years of
      follow-up, 803 premenopausal women were newly diagnosed with invasive breast
      cancer. For women with a BMI below 25 kg/m2, those with a bra cup size of "D or
      larger" had a significantly higher incidence of breast cancer than women who
      reported "A or smaller" (covariate adjusted HR=1.80; 95% CI 1.13-2.88;
      ptrend=0.01). There was no significant association among women with a BMI of 25
      kg/m2 or higher. Stratifying by BMI at age 18 at a cutoff point of 21 kg/m2 gave
      similar results. Larger bra cup size at a young age is associated with a higher
      incidence of premenopausal breast cancer, though this association is limited to
      leaner women.

PMID- 16284955
TI  - Tubal sterilization in relation to breast cancer risk.
AB  - Tubal sterilization methods may damage surrounding tissue, potentially disrupting
      the ovarian blood supply and hormonal functioning, and may decrease breast cancer
      risk. We examined this hypothesis, within the Nurses' Health Study, among 77,511
      women, aged 30-55 years and free of cancer at the start of follow-up in 1976. We
      documented 4,176 cases of invasive breast cancer from 1976 to 2000. Cox
      proportional hazards models, adjusting for multiple breast cancer risk factors,
      provided rate ratios (RR) and 95% confidence intervals (CI). Overall, tubal
      sterilization was not associated with breast cancer risk (RR=0.95, 95% CI=0.88
      1.03). However, tubal sterilizations performed from 1970 to 1974 were inversely
      associated with risk (RR=0.84, 95% CI=0.73-0.97), while procedures performed in
      other years were not associated with risk. Among women with procedures performed
      in 1970-1974, those who were >or=35 years old at the time of sterilization were
      at the lowest risk (RR=0.81, 95% CI=0.66-0.98), while younger women had a
      suggested decreased risk (RR=0.87, 95% CI=0.72-1.06). Overall, tubal
      sterilization was not associated with breast cancer risk. However, a modest
      inverse association was observed at a time when the potentially destructive
      unipolar electrocautery method was commonly used, providing some support for an
      association between lower lifetime exposure to hormones and a decreased risk of
      breast cancer.

PMID- 16284956
TI  - Crystal structure of Escherichia coli DkgA, a broad-specificity aldo-keto
      reductase.

PMID- 16284957
TI  - Total and specific fluid consumption as determinants of bladder cancer risk.
AB  - We pooled the data from 6 case-control studies of bladder cancer with detailed
      information on fluid intake and water pollutants, particularly trihalomethanes
      (THM), and evaluated the bladder cancer risk associated with total and specific
      fluid consumption. The analysis included 2,729 cases and 5,150 controls. Odds
      ratios (OR) and 95% confidence intervals (CI) for fluid consumption were adjusted
      for age, gender, study, smoking status, occupation and education. Total fluid
      intake was associated with an increased risk of bladder cancer in men. The
      adjusted OR for 1 l/day increase in intake was 1.08, (95% CI 1.03-1.14, p-value
      for linear trend <0.001), while no trend was observed in women (OR=1.04, 0.94
      1.15; p-value=0.7). OR was 1.33 (1.12-1.58) for men in the highest category of
      intake (>3.5 l/day) as compared to those in the lowest (<or=2 l/day). An
      increased risk was associated with intake of tap water. OR for >2 l/day vs.
      <or=0.5 l/day was 1.46 (1.20-1.78), with a higher risk among men (OR=1.50, 1.21
      1.88). No increased risk was observed for the same intake groups of nontap water
      in men (OR=0.97, 0.77-1.22) or in women (OR=0.85, 0.50-1.42). Increased bladder
      cancer risks were observed for an intake of >5 cups of coffee daily vs. <5 and
      for THM exposure, but neither exposure confounded or modified the OR for tap
      water intake. The association of bladder cancer with tap water consumption, but
      not with nontap water fluids, suggests that carcinogenic chemicals in tap water
      may explain the increased risk.

PMID- 16284958
TI  - Thermal denaturation of a recombinant mouse amelogenin: circular dichroism and
      differential scanning calorimetric studies.
AB  - Conformational analyses of a recombinant mouse tooth enamel amelogenin (rM179)
      were performed using circular dichroism (CD), fluorescence, differential scanning
      calorimetry, and sedimentation equilibrium studies. The results show that the far
      UV CD spectra of rM179 at acidic pH and 10 degrees C are different from the
      spectra of random coil in 6 M GdnHCl. A near-UV CD spectrum of rM179 at 10
      degrees C is similar to that of rM179 in 6 M GdnHCl, which indicates that
      aromatic residues of native structure are exposed to solvent and rotate freely.
      Far-UV CD values of rM179 at 80 degrees C are different from that of random-coil
      structure in 6 M GdnHCl, which suggests that rM179 at 80 degrees C has specific
      secondary structures. A gradual thermal transition was observed by far-UV CD,
      which is interpreted as a weak cooperative transition from specific secondary
      structures to other specific secondary structures. The fluorescence emission
      maximum for the spectrum due to Trp residues in rM179 at 10 degrees C shows the
      same fluorescence emission maximum as rM179 in 6 M GdnHCl and amino acid Trp,
      which indicates that the three Trp in rM179 are exposed to solvent. Deconvolution
      of differential scanning calorimetry curve gives the population of three states
      (A, I, and C states). These results indicate that three states (A, I, and C) have
      specific secondary structures, in which hydrophobic and Trp residues are exposed
      to the solvent. The thermodynamic characteristics of rM179 are unique and
      different from a typical globular protein, proline-rich peptides, and a molten
      globule state.

PMID- 16284959
TI  - T cells specific for HPV16 E7 epitopes in patients with squamous cell carcinoma
      of the oropharynx.
AB  - Squamous cell carcinomas of the oropharynx (SCCO) are often infected with
      oncogenic human papilloma virus (HPV) subtype 16. To determine the frequency of T
      cells specific for human leukocyte antigen (HLA)-A2.1 restricted HPV16 E7 protein
      derived epitopes, tetramer analysis was performed using peripheral blood
      lymphocytes of 20 HLA-A2.1+ patients and 20 HLA-A2.1+ healthy individuals.
      Tetramers specific for 3 HPV16 peptides (E711-20, E782-90 and E786-93), an
      influenza matrix peptide (a model recall antigen) or an HIV reverse transcriptase
      peptide (a model novel antigen) were used in multicolor flow analysis. The HPV
      specific T-cell frequencies were correlated with the HPV16 E7 and p16 status in
      tumor sections. In vitro stimulation (IVS) with autologous dendritic cells (DC)
      pulsed with HPV16 E7 epitopes was performed to demonstrate proliferation and
      antitumor activity of the HPV-responsive T cells. Frequencies of CD8+ T cells
      specific for HPV16 E7 peptides were not significantly different in patients with
      SCCO relative to normal donors. However, patients with tumors expressing HPV16 E7
      (60%) and p16 (50%) had an increased frequency (p<0.05) of T cells specific for
      the E711-20 epitope compared to those with tumors negative for both markers.
      HPV16 E711-20 and HPV16 E786-93 specific T cells were expandable upon IVS with
      cognate peptide-pulsed DC and were reactive against peptide-pulsed targets or, in
      case of the E711-20 epitope-specific T cells, against HPV16 E7 expressing CaSki
      cell line. Thus, in patients with HPV16+ SCCO, precursor T cells specific for
      E711-20 epitope are present (1/3,947) in the circulation, are responsive to
      stimulation with the cognate viral peptide and recognize in vitro HPV16 E7+ tumor
      cells. Further studies have to elucidate why those T cells are unable to
      eliminate the tumor in vivo and this might also allow for finding potential
      strategies that will increase the chances of developing a future HPV-based
      vaccine in patients with SCCO.

PMID- 16284960
TI  - Nitric oxide and c-Jun N-terminal kinase are involved in the development of dark
      neurons induced by inflammatory pain.
AB  - Dark neurons, whose morphological characteristics are consistent with those of
      cells undergoing apoptosis, are generated in vivo as an acute or delayed
      consequence of several pathological situations and lesions. The present study was
      designed to evaluate whether inflammatory pain induced by injection of formalin
      to the rat hind paw lead to the formation of dark neurons in the dorsal horn of
      the lumbar spinal cord in rat. Since nitric oxide (NO) and c-Jun N-terminal
      Kinase (JNK) pathway are involved in the mechanisms of pain generation and
      degenerative neuronal alteration, their roles were also considered. The methods
      used spectrophotometrical analysis of the serum nitrite (metabolite of NO) and
      histological procedures for detection of dark neurons, following induction of
      inflammatory pain. According to the results, injection of formalin led to an
      increase of the serum nitrite level in both concentration and time-dependent
      manners. Visual inspections of the lumbar spinal cord sections showed that, on
      day 5, following chronic injections of 5% formalin, numbers of dark neurons were
      significantly increased. Acute and chronic administration of 1% or 2.5% formalin
      did not induce any remarkable neuronal alterations in the dorsal horn of the
      lumbar spinal cord. Daily intrathecal administration of quercetin (inhibitor of
      JNK pathway) 100 microg/rat, or 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3
      oxide (PTIO; NO scavenger) 30 mug/rat before injection of 5% formalin led to a
      reliable reduction in the number of dark neurons. These results indicate that
      induction of inflammatory pain for longer periods may result in a serious central
      disorder. Pretreatment with neutralizers or inhibitors of NO and JNK may exert a
      neuroprotective effect in this regard.

PMID- 16284961
TI  - Computational characterization of the sequence landscape in simple protein
      alphabets.
AB  - We characterize the "sequence landscapes" in several simple, heteropolymer models
      of proteins by examining their mutation properties. Using an efficient flat
      histogram Monte Carlo search method, our approach involves determining the
      distribution in energy of all sequences of a given length when threaded through a
      common backbone. These calculations are performed for a number of Protein Data
      Bank structures using two variants of the 20-letter contact potential developed
      by Miyazawa and Jernigan [Miyazawa S, Jernigan WL. Macromolecules 1985;18:534],
      and the 2-monomer HP model of Lau and Dill [Lau KF, Dill KA. Macromolecules
      1989;22:3986]. Our results indicate significant differences among the energy
      functions in terms of the "smoothness" of their landscapes. In particular, one of
      the Miyazawa-Jernigan contact potentials reveals unusual cooperative behavior
      among its species' interactions, resulting in what is essentially a set of phase
      transitions in sequence space. Our calculations suggest that model-specific
      features can have a profound effect on protein design algorithms, and our methods
      offer a number of ways by which sequence landscapes can be quantified.

PMID- 16284962
TI  - Sex differences in juvenile rhesus macaque (Macaca mulatta) agonistic screams:
      life history differences and effects of prenatal androgens.
AB  - This study investigated sex differences in juvenile rhesus macaque (Macaca
      mulatta) vocal behavior during agonistic contexts, and the effects of prenatal
      androgens on these differences. A total of 59 subjects (5-8 per treatment group)
      received exogenous androgen (testosterone enanthate), an anti-androgen
      (flutamide) or vehicle injections (DMSO) for 30 or 35 days during the second
      (early) or third (late) trimester of pregnancy. An additional 19 unmanipulated
      controls were included in the analysis. Screams by juvenile males and females
      between the ages of 1 and 3 years were compared to the screams of adult female
      exemplars using a discriminant function analysis. Juvenile females produced more
      adult-female like screams than did juvenile males. Females exposed to androgen
      treatment late in gestation produced a more masculine pattern of screams.
      Flutamide treatment in males either early or late in gestation did not
      significantly affect scream production. Flutamide treatments in females late in
      gestation, however, masculinized scream production. Androgen treatments
      administered late in gestation hyper-masculinized male scream production. No sex
      differences in the contextual usage of screams emerged. These findings suggest
      that both life history differences and the early hormone environment contribute
      to sex differences in juvenile rhesus macaque vocal production.

PMID- 16284963
TI  - Childcare as a stabilizing influence on HPA axis functioning: a reevaluation of
      maternal occupational patterns and familial relations.
AB  - The influence of family relations, maternal occupational characteristics, and
      childcare1The UK terms "childcare," childcare centres' and "nurseries" are used
      throughout this paper to define group care for children prior to starting their
      first year of formal schooling at age 4 years and are used synonymously with the
      American terms "day-care" and "preschool." This form of group care is provided in
      a formal setting, outside the family home and excludes "childminding" (i.e.,
      childcare that may be group based and offered at the home of the care
      provider/childminder). In the UK, this form of childcare is offered from zero to
      4 years old. Children are separated according to their age into small groups
      usually consisting of 10-15 children. In the present study, all children were in
      the preschool-aged group (3-4 years old). Where childcare of a different or more
      generic form is referred to, then this has been made clear in the context or
      stated in the text. utilization on preschool children's cortisol production were
      investigated in 56 mother-child dyads. Family characteristics and maternal
      employment, childcare and child temperament were reported by mothers. Morning and
      evening levels of children's salivary cortisol were obtained. Children in highly
      expressive or reserved families exhibited higher cortisol levels compared to
      children in moderately expressive families. Elevated levels of cortisol were
      detected in children of mothers reporting low levels of job role quality or high
      levels of emotional exhaustion. Frequent childcare use was found to protect
      children against the physiological effects of low maternal job role quality and
      emotional exhaustion. Findings underscore the pervasive role of the family as set
      within an external support system and highlight the potential physiological
      impact of these interacting contexts for children. Further research is needed to
      fully understand current findings and to develop appropriate psycho-physiological
      interventions.

PMID- 16284964
TI  - Maternal influences on adult stress and anxiety-like behavior in C57BL/6J and
      BALB/cJ mice: a cross-fostering study.
AB  - The quality of maternal care during early life has a dramatic impact on later
      stress reactivity and anxiety. Two inbred mouse strains, C57BL/6J and BALB/cJ,
      differ in levels of maternal care, stress reactivity, and anxiety-like behavior
      in adulthood. However, the relative contribution of early environmental factors
      and genetic predisposition to differences in these strains is not known. Maternal
      care, plasma corticosterone levels, emotionality, and hippocampal and
      paraventricular nucleus (PVN) glucocorticoid receptor mRNA levels were measured
      in adult C57BL/6J and BALB/cJ mice. Litters were then cross-fostered and anxiety
      like behavior and stress reactivity was assessed in adulthood. Significantly less
      maternal care and elevated stress-induced corticosterone and emotionality was
      observed in BALB/cJ compared to C57BL/6J mice. Yet, no strain differences were
      found in hippocampal or paraventricular nucleus glucocorticoid receptor mRNA
      levels. Cross-fostering did alter anxiety-like behavior and basal corticosterone
      levels, which suggests that while genetic differences account for some of the
      variations between these two strains early rearing conditions also contribute.

PMID- 16284965
TI  - Conjugate limb coordination after experience with an interlimb yoke: evidence for
      motor learning in the rat fetus.
AB  - This study investigated the capacity of the E20 rat fetus to adaptively alter
      patterns of interlimb coordination in a prenatal model of motor learning. Fetal
      limb movement was manipulated with an interlimb yoke, consisting of a fine thread
      attached at the ankles, which created a physical linkage between two limbs.
      Exposure to the yoke resulted in a gradual increase in conjugate movements of the
      yoked limbs during a 30-min training period, which persisted after removal of the
      yoke. Training effects were evident when the yoke was applied to two hindlimbs,
      two forelimbs, or a homolateral forelimb-hindlimb pair. A savings in the rate of
      acquisition also was observed when fetuses experienced yoke training in a second
      session. These data argue that the rat fetus can respond to kinesthetic feedback
      resulting from variation in motor performance, which suggests that experience
      contributes to the development of coordinated motor behavior before birth.

PMID- 16284966
TI  - Effects of different opportunities for social interaction on the play fighting
      behavior in male and female golden hamsters (Mesocricetus auratus).
AB  - After social isolation, animals play significantly more than nonisolated animals.
      However, it is not always possible to affirm that the effect of the social
      isolation is due to the lack of play. Experimentally, selective privation has
      been used, such as allowing the animals to play during periods of the day. In the
      present study, two experiments were carried out to verify the possible
      differences in the play fighting behavior of golden hamsters that were allowed to
      have different daily periods of social interaction (10 min, 1 hr, or 2 hr).
      Through the statistical analysis, it was shown that males play more than females
      and that periods of up to 2 hr daily for interaction are insufficient to avoid
      the short-term effects of isolation. It is concluded that a period of daily
      social interaction greater than 2 hr is needed to offset the effects of social
      isolation in golden hamsters.

PMID- 16284967
TI  - It's not that bad: error introduced by oral stimulants in salivary cortisol
      research.
AB  - Evidence that oral stimulants can produce interference effects in salivary
      cortisol assays has led to advice to avoid their use. However, in studies with
      young children, the use of these saliva-producing substances increases compliance
      with collection procedures. Four experiments are described to examine the effects
      of two commonly used stimulants, SweetTarts and Koolaid. Across these
      experiments, interference effects produced by different quantities of these
      stimulants (0.025, 0.1, and 0.2 g) and those produced in two commonly used
      assays, DELFIA and EIA, were explored. The impact of using cotton rolls soaked
      with an oral stimulant prior to saliva collection was also examined. In general,
      oral stimulants did not affect the rank ordering of cortisol values, as the
      results for stimulant-treated samples were highly correlated with those of
      untreated samples (approximately .90 for serially collected samples and .95 for
      aliquots of the same saliva pool). Depending on which assay was used, however,
      oral stimulants increased or decreased the cortisol levels reported, with effects
      sizes in the small to medium range. Thus, oral stimulants should not be used with
      only a portion of the subjects in a study, nor should researchers assay stimulant
      treated samples from the same study using different assays. When used sparingly,
      oral stimulants can be employed without compromising the quality of salivary
      cortisol data.

PMID- 16284968
TI  - Tracheobronchopathia osteochondroplastica in a 9-year-old girl.
AB  - Tracheobroncopathia osteochondroplastica (TO) is a rare disease of adult males
      characterized by osteocartilagious submucosal nodules protruding into the airway
      lumen, causing variable degrees of airway obstruction. Here we describe a case of
      TO in a 9-year-old girl patient presenting with chronic cough, along with a brief
      review of this rare benign condition.

PMID- 16284969
TI  - Developmental changes in the functional brain responses of adolescents to images
      of high and low-calorie foods.
AB  - We examined cerebral responses to visually presented food images in children and
      adolescents. Eight healthy normal-weight females (ages 9-15) underwent functional
      magnetic resonance imaging (fMRI) while viewing photographs of high- and low
      calorie foods and dining utensils. In general, food images yielded significant
      activation within the inferior orbitofrontal cortex, hippocampus, and fusiform
      gyri. High calorie food images activated the left hippocampus and subgenual
      cingulate, and age correlated positively with activity within the orbitofrontal
      cortex but negatively with activity within the anterior cingulate gyrus. Low
      calorie foods activated the fusiform gyrus and demonstrated age-related increases
      in the left superior temporal gyrus and anterior cingulate. Utensils activated
      the fusiform gyrus and showed age-related increases in the prefrontal cortex.
      Data were also compared statistically to a sample of adults exposed to the same
      stimulus conditions. Findings support a developmental model of adolescent
      maturation whereby age-related changes in cerebral functioning develop from lower
      order sensory processing toward higher-order processing of stimuli via prefrontal
      cortical systems involved in reward anticipation, self-monitoring, and behavioral
      inhibition.

PMID- 16284970
TI  - Functional vulnerability of developing central nervous system to maternal
      thiamine deficiencies in the rat.
AB  - Thiamine deficiency (B1 vitamin) was induced during three periods of rat central
      nervous system (CNS) ontogenesis. Females were fed a thiamine deficient diet such
      that developing offspring were exposed either to pre-, peri-, or postnatal
      thiamine deficiency. To control the effects of undernourishment generated by
      different thiamine deficiencies, every treatment group had its own pair-fed
      control pup from a non drug-treated but undernourished dam. Seven different
      developmental abilities (exploratory activity, emotional reaction, hind paws
      lifting reflex, wire grasping times, crawling and leap execution latencies, and
      nociception) were recorded in the offspring from the 10th to the 45th postnatal
      day. The vulnerability of developing brain to the specific lack of B1 vitamin
      increases from prenatal (28%) to perinatal (43%) and postnatal periods (57%).

PMID- 16284971
TI  - Regularities and diversity in developmental pathways: mother-infant relationships
      in hamadryas baboons.
AB  - Change, stasis, stability, discontinuity, orderliness, and diversity are all
      potential characteristics of developmental systems. This study uses multilevel
      modeling to characterize the normative developmental pathways of the early social
      relationships of 23 mother-infant pairs embedded in a multilayered colony of
      hamadryas baboons (Papio hamadryas hamadryas). The relationships were assessed by
      means of 27 behavioral measures that were collected during 100-220 focal sampling
      sessions per infant, from birth to 380 days of age (25 two-week age intervals).
      Seventy four percent of the behavioral measures exhibited an age-related pattern.
      Infant age, however, was not predictive of the rate of the behaviors relating to
      the management of mother-infant conflicts. This study provides empirical evidence
      that the development of mother-infant relationships may involve periods of change
      and stasis, overall orderliness, and diversity as well as canalization of
      developmental pathways. We believe that growth curve analysis can be useful to
      tackle various hot issues in the study of behavioral development.

PMID- 16284972
TI  - Ensemble-based signatures of energy propagation in proteins: a new view of an old
      phenomenon.
AB  - The ability of a protein to transmit the energetic effects of binding from one
      site to another constitutes the underlying basis for allosterism and signal
      transduction. Despite clear experimental evidence indicating the ability of
      proteins to transmit the effects of binding, the means by which this propagation
      is facilitated is not well understood. Using our previously developed ensemble
      based description of the equilibrium, we investigated the physical basis of
      energy propagation and identified several fundamental and general aspects of
      energetic coupling between residues in a protein. First, partitioning of a
      conformational ensemble into four distinct sub-ensembles allows for explanation
      of the range of experimentally observed coupling behaviors (i.e., positive,
      neutral, and negative coupling between various regions of the protein structure).
      Second, the relative thermodynamic properties of these four sub-ensembles define
      the energetic coupling between residues as either positive, neutral, or negative.
      Third, analysis of the structural and thermodynamic features of the states within
      each sub-ensemble reveals significant variability. This third result suggests
      that a quantitative description of energy propagation in proteins requires an
      understanding of the structural and energetic features of more than just one or a
      few low-energy states, but also of many high-energy states. Such findings
      illuminate the difficulty in interpreting energy propagation in proteins in terms
      of a structural pathway that physically links coupled sites.

PMID- 16284973
TI  - Molecular markers of head and neck squamous cell carcinoma: promising signs in
      need of prospective evaluation.
AB  - BACKGROUND: The aim of this article is to review recent developments in the
      biological understanding of head and neck squamous cell carcinomas. METHODS AND
      RESULTS: We describe the markers according to their function and their prognostic
      or predictive roles. Some associations can be found between molecular markers and
      invasiveness, aggressiveness, degree of differentiation, and tumor stage, but
      only a few clinical studies have shown an impact on prognosis. In addition,
      despite an increasing number of articles relating to this topic, the small number
      of patients included in the studies reported reduces the clinical implications of
      these results. Few studies applied a more comprehensive molecular analysis
      approach, such as DNA microarrays or differential expression profiling by
      polymerase chain reaction, to identify a combination of markers that could be
      more informative than a single molecular marker. CONCLUSION: Some progress has
      been made with respect to molecular markers and head and neck cancers.
      Translational and prospective, hypothesis-driven research must proceed with
      sufficient rigor to facilitate the clinical applicability of such results.

PMID- 16284974
TI  - Protective mechanisms of head and neck squamous cell carcinomas from immune
      assault.
AB  - Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy that is
      the sixth most common neoplasm in the world. Despite advances in treatments
      involving surgery, radiation, and chemotherapy, the 5-year survival has remained
      at less than 50% for the past 30 years, primarily because of local recurrences.
      Thus, the possibility of immunotherapeutic approaches for patients with HNSCC has
      gained interest. Unfortunately, patients with HNSCC have profound immune defects
      that are associated with increased recurrence. This review aims to provide an
      overview of both the defensive and immune subversive mechanisms by which patients
      with HNSCC can protect themselves from immune antitumor assault.

PMID- 16284976
TI  - Clinical applications of genomics in head and neck cancer.
AB  - Advances in gene expression analyses have allowed global assessment of expressed
      genes in clinical samples. Gene expression profiles derived from clinical
      specimens have been used to distinguish differences in tumors that are not
      obvoius by clinical, radiographic, or histologic characteristics. Despite its
      common histology and presentation, head and neck squamous cell carcinoma (HNSCC)
      is associated with widely varying clinical behavior and response to therapy.
      Currently, clinicians have a dearth of tools to predict response to therapy or to
      identify patients at high risk of poor outcome. Recently comprehensive analyses
      of gene expression patterns of individual tumors have shown promise to improve
      discovery of biomarkers for 1) progression of premalignant lesions, 2) disease
      presence or absence, 3) prediction of clinical outcome, and 4) identification of
      targets for therapy. In this review, we will discuss advances, limitations and
      future directions of genomics as it applies to HNSCC.

PMID- 16284975
TI  - Spontaneous remission of primary hyperparathyroidism: a case report and meta
      analysis of the literature.
AB  - BACKGROUND: In a minority of patients, primary hyperparathyroidism spontaneously
      remits either by autoinfarction or by hemorrhage into or around the adenoma. We
      describe a case of autoparathyroidectomy occurring in a 63-year-old man 9 years
      after three parathyroid glands were removed during a total thyroidectomy. This
      case is compared with 50 previously reported cases of autoparathyriodectomy, and
      a meta-analysis is performed. METHODS: Case report, literature review, and meta
      analysis were done using statistical software (SigmaStat 2.0, SPSS, Chicago).
      RESULTS: Fifty cases of autoparathyroidectomy were summarized according to the
      three etiologies. The greatest biochemical aberration was found in the acute
      intracapsular hemorrhage group, with [Ca(++)] falling from a mean 15.1 mg/dL to
      8.9 mg/dL. The average drop in parathyroid hormone was 69% across all groups,
      comparing favorably to surgical resection. CONCLUSIONS: Autoparathyroidectomy is
      a rare but described outcome of unoperated primary hyperparathyroidism that may
      delay or supplant operative management.

PMID- 16284977
TI  - Quality of life after free-flap reconstruction in patients with oral and
      pharyngeal cancer.
AB  - BACKGROUND: Our aim was to investigate quality of life and outcome after
      microvascular free-flap reconstruction after oncologic surgery. METHODS: Forty
      four patients with a large carcinoma in the oral cavity, oral pharynx, or
      hypopharynx underwent free-flap surgery with or without radiotherapy. Patients
      completed the University of Washington Quality-of-Life Questionnaire
      preoperatively and four times during the 12 postoperative months. Survival rates
      and complications were analyzed. RESULTS: Postoperative composite quality-of-life
      scores were significantly lower than before treatment with no significant overall
      improvement during the follow-up. The scores for disfigurement, chewing, speech,
      and shoulder function remained significantly below the preoperative level
      throughout the follow-up. Sociodemographic factors predicted quality of life.
      Heavy drinking and unemployment caused a 2.4-fold and a 4.4-fold increase in risk
      of death, respectively. The rates for overall survival, tumor recurrence, flap
      success, and surgical complications were consistent with previous literature.
      CONCLUSION: Sociodemographic variables affect quality of life and patient
      survival in patients with oral cancer treated with microvascular free-flap
      reconstruction.

PMID- 16284978
TI  - Impact of endoscopic screening on early detection of hypopharyngeal cancer.
AB  - BACKGROUND: The aim was to investigate whether periodic pharyngolaryngoscopy
      screening in high-risk patients with preceding carcinoma of the upper
      aerodigestive tract can detect early hypopharyngeal cancer and preserve the
      larynx. METHODS: The records of 122 patients with hypopharyngeal cancer were
      retrospectively reviewed. Patients were divided into the following two groups:
      (1) the screening (SCR) group (n = 65), patients whose hypopharyngeal cancer was
      detected by pharyngolaryngoscopy screening; and (2) the symptom (SYMP) group (n =
      57), patients whose cancer was discovered by any symptoms. Patients' demographics
      and larynx preservation were compared. RESULTS: The number of patients with
      clinical stage I to IV disease at diagnosis was 44, 14, three, four for the SCR
      group, respectively, and six, six, 15, 30 for the SYMP group, which was
      significantly different (p < .0001). The rate of larynx preservation after
      radical treatment was 79.4% for the SCR group and 45.4% for the SYMP group (p <
      .001). CONCLUSIONS: Periodic pharyngolaryngoscopy screening in high-risk patients
      may contribute to detecting early hypopharyngeal cancer. Early detection of
      hypopharyngeal cancer may enhance the rate of larynx preservation and improve the
      quality of life.

PMID- 16284980
TI  - Prospective evaluation of the retrograde percutaneous translaryngeal tracheostomy
      (Fantoni procedure) in a surgical intensive care unit: technique and results of
      the Fantoni tracheostomy.
AB  - BACKGROUND: Controversy surrounds the safety and practicality of the retrograde
      percutaneous translaryngeal tracheostomy (Fantoni procedure) compared with other
      percutaneous methods. METHODS: We used the Fantoni tracheostomy for 245 patients
      in our intensive care unit (ICU) over a period of 3 years 6 months and conducted
      a prospective analysis. RESULTS: We are able to report a low incidence of
      complications (1.2%) with the Fantoni procedure. Advantages of the method are
      reduced tissue trauma and optimal adaptation of the stoma to the cannula, leading
      to less stomal bleeding and fewer infectious complications. We observed no
      procedure-related mortality. Under mandatory bronchoscopic control, proper
      puncture location and cannula placement are ensured, which prevents tracheal wall
      injury and paratracheal placement of the cannula. CONCLUSIONS: Our experience
      shows that the major advantage of the use of the Fantoni tracheostomy is the
      retrograde dilatation of the stoma, which prevents serious complications compared
      with other techniques.

PMID- 16284981
TI  - New horizon of bioabsorbable stent.

PMID- 16284982
TI  - Glycoprotein IIb-IIIa receptor inhibition with eptifibatide in percutaneous
      intervention for symptomatic peripheral vascular disease: the circulate pilot
      trial.
AB  - The benefits of glycoprotein (GP) IIb-IIIa inhibitors in percutaneous coronary
      intervention are well established, but the experience with these agents in the
      setting of peripheral interventions is limited. In this single-center pilot
      trial, the safety and feasibility of adjunctive treatment with the GP IIb-IIIa
      inhibitor eptifibatide (INTEGRILIN, Millennium Pharmaceuticals, Inc., Cambridge,
      Massachusetts, and Schering-Plough Corporation, Kenilworth, New Jersey) was
      evaluated in 85 patients undergoing percutaneous transluminal angioplasty or
      stenting for severe claudication or critical limb ischemia. Eptifibatide
      treatment was safe, with low rates of major bleeding (3.5%) and thrombocytopenia
      (1.2%); one patient developed a post-procedure compartment syndrome requiring
      fasciotomy. The procedure was technically successful (defined as <30% residual
      stenosis or >50% increase in vessel diameter) in 84 of 85 (98.8%) patients. None
      of the patients required target vessel revascularization (TVR) during
      hospitalization, and only 1 patient (1.2%) required TVR within 30 days. These
      results demonstrate that adjunctive use of eptifibatide during percutaneous
      peripheral intervention is safe and supports further studies to establish the
      potential efficacy of GP IIb-IIIa inhibitors in this setting.

PMID- 16284983
TI  - To achieve (E)quality health care for childhood cancer survivors.

PMID- 16284984
TI  - Does maintenance/consolidation chemotherapy have a role in the management of
      small cell lung cancer (SCLC)? A metaanalysis of the published controlled trials.
AB  - BACKGROUND: The role of maintenance/consolidation chemotherapy was assessed in
      the management of small cell lung cancer (SCLC) via a metaanalytic approach.
      METHODS: The Medline and Cochrane databases were searched for relevant randomized
      clinical trials that compared maintenance chemotherapy with follow-up. Quality of
      trials was assessed by European Lung Cancer Working Party (ELCWP) score. Odds
      ratios and rate differences were used as the effect size. Mantel-Haenszel tests
      with fixed and random effect models were conducted for 1- and 2-year overall
      survival (OAS) and progression-free survival (PFS). RESULTS: Fourteen relevant
      randomized clinical trials to date, encompassing 2550 patients, with trial sizes
      ranging from 36 to 610, were identified. Both 1- and 2-year mortality were
      reduced with maintenance/consolidation chemotherapy. With the fixed model, odds
      ratios for 1- and 2-year OAS were 0.67 (95% confidence interval [CI] = 0.56
      0.79), P < 0.001, and also 0.67 (95% CI = 0.53-0.86), P < 0.001. Likewise, 1- and
      2-year PFS were better with maintenance/consolidation chemotherapy, with odds
      ratios of 0.49 (95% CI = 0.37-0.63), P < 0.001, and 0.64 (95% CI = 0.45-0.92), P
      < 0.015. The random model gave similar results. In accordance, maintenance
      chemotherapy improved 1- and 2-year OAS by 9% (from 30-39%) and 4% (from 10-14%),
      respectively. Similarly, 1- and 2-year PFS were also improved. CONCLUSION:
      Maintenance/consolidation chemotherapy improves survival in SCLC. New randomized
      clinical trials are needed to further refine the place of this approach in the
      management of SCLC.

PMID- 16284986
TI  - Estimating late adverse events using competing risks after autologous stem-cell
      transplantation in aggressive non-Hodgkin lymphoma patients.
AB  - BACKGROUND: Consolidative autologous stem-cell transplantation (ASCT) is a
      valuable option in high-risk or disease recurrence large-cell non-Hodgkin
      lymphoma patients (NHL); however, its long-term toxicity must still be assessed.
      METHODS: Among the 439 lymphoma patients transplanted at our institution from
      January 1, 1993, to January 1, 2002, 158 exhibited aggressive NHL. The median age
      of the patients was 46 years (range, 18-69), 98 males and 60 females. Ninety
      (57%) patients received first-line ASCT. The median number of prior chemotherapy
      regimens was 2 (range, 1-10). Thirty-eight (24%) patients received total body
      irradiation conditioning. Here we report the adverse events which occurred at
      least 30 days after ASCT and before disease recurrence. RESULTS: After a median
      follow-up of 3 years, the overall and disease-free survival rates were 61% and
      55%, respectively. Sixty-eight late adverse events affected 43 (27%) patients,
      leading to a cumulative incidence of 34% at 3 years. Infections were the most
      frequent adverse events (n = 13), followed by neurologic (n = 12), pulmonary (n =
      6), or cardiovascular (n = 4). Eight malignancies were diagnosed (six solid, two
      hematologic), leading to a cumulative incidence of 3.7% at 3 years. Taking into
      account the competing risks, multivariate analysis revealed that the number of
      progressions (relative risk [RR] = 2.68) and a mitoxantrone-containing
      conditioning regimen (RR = 2.98) significantly increased the incidence of late
      toxicity. CONCLUSION: ASCT is effective in patients with aggressive NHL with a
      poor prognosis. However, careful long-term follow-up of survivors is recommended
      because of the increase in malignant and nonmalignant toxicities.

PMID- 16284985
TI  - A randomized, postremission comparison of four courses of standard-dose
      consolidation therapy without maintenance therapy versus three courses of
      standard-dose consolidation with maintenance therapy in adults with acute myeloid
      leukemia: the Japan Adult Leukemia Study Group AML 97 Study.
AB  - BACKGROUND: A major concern in the treatment of patients with acute myeloid
      leukemia (AML) is how to prevent disease recurrences. Although intensive
      consolidation therapy has proven useful, the effectiveness of maintenance therapy
      remains controversial. METHODS: Seven hundred eighty-nine patients ages 15-64
      (median: 45 yrs) with de novo AML received induction therapy, which consisted of
      cytosine arabinoside (at a dose of 100 mg/m(2) on Days 1-7) and idarubicin (at a
      dose of 12 mg/m(2) on Days 1-3). The patients who achieved complete remission
      (CR) were then randomized into groups that received either four courses of
      standard-dose consolidation therapy without maintenance (Arm A) or three courses
      of standard-dose consolidation and six courses of maintenance therapy (Arm B).
      RESULTS: In total, 78.7% of patients achieved CR. The 5-year overall survival
      (OS) rate for the 789 eligible patients was 46.9%, and the disease-free survival
      (DFS) rate for the 621 patients who achieved CR was 32.9%. The 5-year OS rate for
      Arm A was 52.4%, and 58.4% for Arm B (P = 0.599). The 5-year DFS rate for the
      patients who achieved CR was 35.8% in Arm A and 30.4% in Arm B (P = 0.543). In
      analyzing the data according to the risk groups, no statistical difference was
      observed either in the 5-year OS rate or in the 5-year DFS rate between the 2
      arms. CONCLUSIONS: In the current study, the Japan Adult Leukemia Study Group's
      conventional postremission therapy (three courses of standard-dose consolidation
      and six courses of maintenance therapy) was replaced successfully by a shorter
      duration of four courses of standard-dose consolidation therapy without the need
      for additional maintenance therapy.

PMID- 16284987
TI  - Risk factors for chemotherapy-associated venous thromboembolism in a prospective
      observational study.
AB  - BACKGROUND: The incidence of venous thromboembolism (VTE) is increased in cancer,
      but little information is available about risk factors in cancer patients on
      chemotherapy. METHODS: We analyzed data from a prospective, multicenter
      observational study to determine the frequency and risk factors for VTE in
      ambulatory cancer patients initiating a new chemotherapy regimen. The association
      of VTE with clinical variables was characterized using univariate and
      multivariate analysis. RESULTS: Among 3003 patients treated with at least one
      cycle of chemotherapy, VTE occurred in 58 (1.93%) over a median follow-up of 2.4
      months (0.8%/mo). The incidence varied significantly by site of cancer (P = 0.01)
      with highest rates in upper gastrointestinal (2.3%/mo) and lung cancer (1.2%/mo),
      and lymphoma (1.1%/mo). An elevated prechemotherapy platelet count was
      significantly associated with an increased rate of VTE (P for trend = 0.005). The
      incidence of VTE was 3.98% (1.66%/mo) for patients with a prechemotherapy
      platelet count > or = 350,000, compared with 1.25% (0.52%/mo) for patients with
      platelet counts of < 200,000 (P for trend=0.0003). In multivariate analysis, a
      prechemotherapy platelet count of > or = 350,000/mm(3) (adjusted OR 2.81, 95% CI
      1.63-4.93, P = 0.0002), site of cancer, hemoglobin < 10 g/dL or use of
      erythropoietin, and use of white cell growth factors in high-risk sites of cancer
      were significantly associated with VTE. CONCLUSIONS: Symptomatic VTE is a
      frequent complication of chemotherapy. The prechemotherapy platelet count is a
      unique risk factor and can help identify high-risk patients for future trials of
      thromboprophylaxis.

PMID- 16284988
TI  - Phase II study of transdermal estradiol in androgen-independent prostate
      carcinoma.

PMID- 16284991
TI  - BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma
      cases.
AB  - BACKGROUND: It is believed that BRCA1 and BRCA2 germline mutations account for
      the majority of hereditary ovarian carcinomas; however, to the authors'
      knowledge, there are scant data on the prevalence and spectrum of mutations,
      genotype/phenotype correlations, tumor histology, and family history
      characteristics. To address this gap, the authors conducted a population-based
      study of 232 incident epithelial ovarian carcinomas in the Tampa Bay area.
      METHODS: Genetic testing for the BRCA1 and BRCA2 genes was performed through full
      sequencing and BRCA1 rearrangement testing. RESULTS: Of 209 women with invasive
      ovarian carcinoma, 32 women (15.3%) had mutations in BRCA1 or BRCA2, including 20
      BRCA1 mutations and 12 BRCA2 mutations. Of the BRCA2 mutations, 58% were outside
      the "ovarian cancer cluster region" (OCCR). Variants of uncertain significance
      were detected in 8.2% of women with invasive ovarian carcinoma. No mutations were
      identified in women with borderline or invasive mucinous tumors. Among the BRCA
      mutation-positive women, 63% had serous tumors. A family history of breast and/or
      ovarian carcinoma was reported in 65%, 75%, and 43.5% of relatives of BRCA1
      carriers, BRCA2 carriers, and non-BRCA1/BRCA2 carriers, respectively.
      CONCLUSIONS: The data from this study suggested that 1) previous studies may have
      underestimated the frequency of BRCA1 and BRCA2 mutations in ovarian carcinomas,
      especially outside the OCCR; 2) it may be reasonable to offer genetic counseling
      to any woman with an invasive, nonmucinous epithelial ovarian tumor; and 3) among
      patients with invasive ovarian carcinoma, family history is not sufficiently
      accurate to predict mutation status.

PMID- 16284990
TI  - The addition of rituximab to fludarabine improves clinical outcome in untreated
      patients with ZAP-70-negative chronic lymphocytic leukemia.
AB  - BACKGROUND: Clinical trials of monoclonal antibodies in combination with
      chemotherapy have reported previously unattained response rates in patients with
      B-cell chronic lymphocytic leukemia (B-CLL); however, the analysis of ZAP-70
      protein and/or CD38 may explain better the discordant outcomes independent of
      treatment. METHODS: The authors conducted a Phase II study, in which rituximab
      was added to fludarabine for patients with symptomatic, untreated CLL, to
      evaluate clinical outcomes. Sixty patients with B-CLL received 6 monthly courses
      of fludarabine (25 mg/m(2) for 5 days) followed by 4 weekly doses of rituximab
      (375 mg/m(2)). RESULTS: On the basis of National Cancer Institute criteria, 47 of
      60 patients (78%) achieved a complete remission, 9 of 60 patients (15%) achieved
      a partial remission, and 4 of 60 patients (7%) had no response or progressive
      disease. It is noteworthy that the patients experienced a long progression-free
      survival (PFS) from treatment (68% at 3 yrs). A significantly shorter PFS was
      observed in ZAP-70-positive patients (25% vs. 100% at 3 yrs; P = 0.00005), in
      CD38-positive patients (18% vs. 91% at 3 yrs; P = 0.0002), and in patients who
      had more minimal residual disease (36% vs. 77% at 2.5 yrs; P = 0.001).
      CONCLUSIONS: With the addition of rituximab to fludarabine, improved clinical
      outcomes were obtained, and the stratification of patients by using ZAP-70 and
      CD38 may help clinicians offer more aggressive and/or experimental approaches to
      the treatment of patients with high-risk B-CLL subtypes.

PMID- 16284992
TI  - Transdermal fentanyl in the management of children with chronic severe pain:
      results from an international study.
AB  - BACKGROUND: The current study was conducted to assess the safety and tolerability
      of a transdermal fentanyl delivery system for the relief of chronic pain in a
      pediatric population, and also to validate titration recommendations and
      conversion to transdermal fentanyl from oral opioid therapy. METHODS: This 15-day
      (with 3-month extension), single-arm, open-label trial was conducted at 66 sites
      in 10 countries. A total of 199 pediatric patients (ages 2-16 years) with both
      malignant and nonmalignant conditions who were receiving oral or parenteral
      opioids for moderate to severe chronic pain were enrolled. Transdermal fentanyl
      doses were titrated upward according to the rescue medication consumed during the
      previous application period. Degree of pain was assessed by patients and
      parents/guardians using visual and numeric scales. Level of play and quality of
      life were assessed using the Play Performance Scale (PPS) and the Child Health
      Questionnaire (CHQ). Adverse events were monitored on Days 1-15. Hypoventilation
      and sedation were monitored every 4 hours during the first 72 hours of the study.
      RESULTS: A total of 173 patients completed the primary treatment period and 130
      entered the extension phase. The average daily pain intensity scores were
      reported to have decreased by Day 16 and improvements in the mean PPS scores were
      observed to the end of the extension period. The CHQ scores demonstrated
      improvements in 11 of 12 domains after Month 1 of the extension period.
      CONCLUSIONS: Transdermal fentanyl was found to be a safe and well tolerated
      alternative to oral opioid treatment for children ages 2-16 years who were
      previously exposed to opioid therapy.

PMID- 16284993
TI  - Survivin expression and its relation with proliferation, apoptosis, and
      angiogenesis in brain gliomas.
AB  - BACKGROUND: An unbalance of cell proliferation and cell apoptosis is an important
      mechanism in carcinogenesis, and angiogenesis also plays a crucial role in
      tumorigenesis. Recently, survivin has been identified as an important member of
      the inhibitor of apoptosis protein (IAP) family. Although it has been shown that
      survivin is highly expressed in gliomas, and is associated with tumorigenesis,
      progression, and poor prognosis of gliomas, as yet the relation of survivin
      expression with proliferation, apoptosis, and angiogenesis of gliomas it is still
      unclear. METHODS: Eighty-three cases of brain glioma were chosen and protein
      expressions of survivin and proliferating cell nuclear antigen (PCNA) in glioma
      cells and Factor VIII-related antigen (FVIII-RAg) in vascular endothelial cells
      were investigated by immunohistochemistry. Apoptotic cells of brain glioma were
      screened by TdT-mediated dUTP nick end-labeling (TUNEL), and survivin
      immunoreactivity score (IRS), proliferative index (PI), apoptotic index (AI),
      overall daily growth (ODG), and microvessel density (MVD) in brain gliomas were
      measured. RESULTS: The survivin IRS, PI, AI, ODG, and MVD of brain gliomas were
      3.75 +/- 3.89, 28.39 +/- 19.49%, 1.00 +/- 0.80%, 12.19 +/- 10.21%, and 62.75 +/-
      31.50, respectively, and all of them increased markedly with an increase in the
      pathologic grade of brain gliomas (P < 0.001 for all). PI, ODG, and MVD in the
      survivin-positive group were significantly higher than those in the survivin
      negative group (P < 0.001 for all). PI, ODG, and MVD were positively correlated
      with survivin IRS (P < 0.001 for all). Although there was no significant
      difference between AI in the survivin-positive group or in the survivin-negative
      group (P = 0.108), AI was inversely correlated with survivin IRS (P = 0.005).
      CONCLUSIONS: Survivin is overexpressed in brain gliomas, which may play an
      important role in malignant proliferation, antiapoptosis, and angiogenesis of
      brain gliomas.

PMID- 16284995
TI  - Adsorption of amyloid beta-peptide at polymer surfaces: a neutron reflectivity
      study.
AB  - The adsorption of amyloid beta-peptide at hydrophilic and hydrophobic modified
      silicon-liquid interfaces was characterized by neutron reflectometry. Distinct
      polymeric films were used to obtain noncharged (Formvar), negatively (sodium
      poly(styrene sulfonate)) and positively charged (poly(allylamine hydrochloride))
      hydrophilic as well as hydrophobic surfaces (polystyrene and a polysiloxane
      dodecanoic acid complex). Amyloid beta-peptide was found to adsorb at positively
      charged hydrophilic and hydrophobic surfaces, whereas no adsorbed layer was
      detected on hydrophilic noncharged and negatively charged films. The peptide
      adsorbed at the positively charged film as patches, which were dispersed on the
      surface, whereas a uniform layer was observed at hydrophobic surfaces. The
      thickness of the adsorbed peptide layer was estimated to be approximately 20 A.
      The peptide formed a tightly packed layer, which did not contain water. These
      studies provide information about the affinity of the amyloid beta-peptide to
      different substrates in aqueous solution and suggest that the amyloid fibril
      formation may be driven by interactions with surfaces.

PMID- 16284996
TI  - Radiolysis of confined water: hydrogen production at a high dose rate.
AB  - The production of molecular hydrogen in the radiolysis of dried or hydrated
      nanoporous controlled-pore glasses (CPG) has been carefully studied using 10 MeV
      electron irradiation at high dose rate. In all cases, the H2 yield increases when
      the pore size decreases. Moreover, the yields measured in dried materials are two
      orders of magnitude smaller than those obtained in hydrated glasses. This proves
      that the part of the H2 coming from the surface of the material is negligible in
      the hydrated case. Thus, the measured yields correspond to those of nanoconfined
      water. Moreover, these yields are not modified by the presence of potassium
      bromide, which is a hydroxyl radical scavenger. This experimental observation
      shows that the back reaction between H2 and HO* does not take place in such
      confined environments. These porous materials have been characterized before and
      after irradiation by means of Fourier-transform infrared (FT-IR) spectroscopy,
      electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR)
      techniques, which helps to understand the elementary processes taking place in
      this type of environment, especially the protective effect of water on the
      surface in the case of hydrated glasses.

PMID- 16284994
TI  - Psychiatric disorders and mental health service use in patients with advanced
      cancer: a report from the coping with cancer study.
AB  - BACKGROUND: Psychological morbidity has been proposed as a source of distress in
      cancer patients. This study aimed to: 1) determine the prevalence of diagnosable
      psychiatric illnesses, and 2) describe the mental health services received and
      predictors of service utilization in patients with advanced cancer. METHODS: This
      was a cross-sectional, multi-institutional study of 251 eligible patients with
      advanced cancer. Eligibility included: distant metastases, primary therapy
      failure, nonpaid caregiver, age > or =20 years, stamina for the interview,
      English or Spanish-speaking, and adequate cognitive ability. Trained interviewers
      administered the Structured Clinical Interview for the Diagnostic Statistical
      Manual IV (DSM-IV) modules for Major Depressive Disorder, Generalized Anxiety
      Disorder, Panic Disorder, Post-Traumatic Stress Disorder, and a detailed
      questionnaire regarding mental health service utilization. RESULTS: Overall, 12%
      met criteria for a major psychiatric condition and 28% had accessed a mental
      health intervention for a psychiatric illness since the cancer diagnosis.
      Seventeen percent had discussions with a mental health professional; 90% were
      willing to receive treatment for emotional problems. Mental health services were
      not accessed by 55% of patients with major psychiatric disorders. Cancer patients
      who had discussed psychological concerns with mental health staff (odds ratio
      [OR] = 19.2; 95% confidence interval [95% CI], 8.90-41.50) and non-Hispanic white
      patients (OR = 2.7; 95% CI, 1.01-7.43) were more likely to receive mental health
      services in adjusted analysis. CONCLUSIONS: Advanced cancer patients experience
      major psychiatric disorders at a prevalence similar to the general population,
      but affected individuals have a low rate of utilizing mental health services.
      Oncology providers can enhance utilization of mental health services, and
      potentially improve clinical outcomes, by discussing mental health concerns with
      their patients.

PMID- 16284997
TI  - Kinetic and DFT studies on the photoinduced desorption of sulfur from gold
      nanoparticles loaded on titanium dioxide.

PMID- 16284998
TI  - Improved hydrogen storage of TiF3-doped NaAlH4.

PMID- 16284999
TI  - DFT study of fullerene dimers.
AB  - Several [2+2] dimerization products of a fullerene Cn (n=50, 52, 54, 56, 58, 60)
      in its most stable form are presented and discussed. In total, 34 dimers are
      studied. Only symmetric Cn-Cn dimers (no mixed products) are reported, and only
      dimers of the fullerenes C50 to C58 with bonds between C atoms in adjacent
      pentagons are considered. Geometries were optimized within the framework of
      density functional theory using the Becke-Perdew exchange-correlation functional
      (BP86) in combination with an empirical dispersive energy correction, which
      contributes significantly to the binding energy. The results are discussed in the
      context of the reactivity of adjacent pentagon sites. The lateral interaction
      between fullerenes is found to be stronger for C50 to C58 than for C60, which is
      consistent with recent experimental observations. Further, the possibility of
      polymer formation based on the investigated [2+2] reaction is addressed.

PMID- 16285000
TI  - The trigonal bipyramidal MN3M species: a new kind of aromatic complex containing
      a multiple-fold aromatic N3 subunit.
AB  - A new kind of aromatic trigonal bipyramidal MN3M (M=Be, B, Mg, Al, and Ca)
      species, with all real frequencies, is obtained at the MP2/6-311+G(3d) level. The
      nucleus-independent chemical shift values are -102.16 ppm for the N3 (3-) ring,
      and -74.09, -79.39, -65.06, -74.44, and -62.33 ppm (at the geometrical center of
      the trigonal bipyramid) for BeN3Be, BN3B, MgN3Mg, AlN3Al, and CaN3Ca,
      respectively. Molecular orbital analysis indicates that the regular triangular N3
      (3-) ring and each MN3M species have three aromatic six-electron systems (pi,
      sigma(p), and sigma(s)) and exhibit threefold aromaticity. The CaN3Ca species has
      a very low vertical ionization energy of 3.64 eV at the CCSD(T)/6-311+G(3d)
      level, which is even lower than the ionization energy (3.9 eV) of the Cs atom.
      Therefore, CaN3Ca can be considered as a new superalkali species. A further study
      on the CaN3CaCl molecule confirms the superalkali characteristics of CaN3Ca. Two
      interesting phenomena are explored in the MN3M species: the delocalized electron
      cloud of the N3 subunit is elongated by two M cations, and the electron clouds of
      two M cations are distended by the N3 (3-) ring.

PMID- 16285001
TI  - Combinatorial engineering of a gene therapy vector: directed evolution of adeno
      associated virus.
AB  - BACKGROUND: Viruses are being exploited as vectors to deliver therapeutic genetic
      information into target cells. The success of this approach will depend on the
      ability to overcome current limitations, especially in terms of safety and
      efficiency, through molecular engineering of the viral particles. METHODS: Here
      we show that in vitro directed evolution can be successfully performed to
      randomize the viral capsid by error prone PCR and to obtain mutants with improved
      phenotype. RESULTS: To demonstrate the potential of this technology we selected
      several adeno-associated virus (AAV) capsid variants that are less efficiently
      neutralized by human antibodies. These mutations can be used to generate novel
      vectors for the treatment of patients with pre-existing immunity to AAV.
      CONCLUSIONS: Our results demonstrate that combinatorial engineering overcomes the
      limitations of rational design approaches posed by incomplete understanding of
      the infectious process and at the same time offers a powerful tool to dissect
      basic viral biology by reverse genetics.

PMID- 16285002
TI  - Dystrophin expression in the mdx mouse after localised and systemic
      administration of a morpholino antisense oligonucleotide.
AB  - BACKGROUND: Duchenne and Becker muscular dystrophies are allelic disorders
      arising from mutations in the dystrophin gene. Duchenne muscular dystrophy is
      characterised by an absence of functional protein, while Becker muscular
      dystrophy is usually caused by in-frame deletions allowing synthesis of some
      functional protein. Treatment options are limited, and we are investigating the
      potential of transcript manipulation to overcome disease-causing mutations.
      Antisense oligonucleotides have been used to induce specific exon removal during
      processing of the dystrophin primary transcript and thereby by-pass protein
      truncating mutations. The antisense oligonucleotide chemistry most widely used to
      alter pre-mRNA processing is 2'-O-methyl-modified bases on a phosphorothioate
      backbone. METHODS: The present studies evaluate 2'-O-methylphosphorothioate,
      peptide nucleic acid and morpholino antisense oligonucleotides in the mdx mouse
      model of muscular dystrophy, which has a nonsense mutation in exon 23 of the
      dystrophin gene. RESULTS: We demonstrate dystrophin expression in mdx mouse
      tissues after localised and systemic delivery of a morpholino antisense
      oligonucleotide designed to target the dystrophin exon 23 donor splice site.
      CONCLUSIONS: The stability of the morpholino structural type, and the fact that
      it can be delivered to muscle in the absence of a delivery reagent, render this
      compound eminently suitable for consideration for therapeutic exon skipping to
      address dystrophin mutations.

PMID- 16285003
TI  - Evaluation of the nuclear delivery and intra-nuclear transcription of plasmid DNA
      condensed with micro (mu) and NLS-micro by cytoplasmic and nuclear
      microinjection: a comparative study with poly-L-lysine.
AB  - BACKGROUND: The efficient nuclear delivery of plasmid DNA (pDNA) is essential for
      the development of a promising non-viral gene vector. In an attempt to achieve
      nuclear delivery, NLS-mu, a novel pDNA condenser, was prepared. This consists of
      mu, a highly potent polypeptide for condensing the pDNA, and a SV40 T antigen
      derived nuclear localization signal (NLS(SV40)). METHODS: The utility of NLS-mu
      was assessed in terms of green fluorescent protein (GFP) expression after
      cytoplasmic and nuclear microinjection of GFP-encoding pDNA along with the
      transfection, and compared with mu and poly-L-lysine (PLL). Trans-gene expression
      after cytoplasmic microinjection was affected by the efficiencies of nuclear
      transfer and following intra-nuclear transcription. To evaluate the nuclear
      transfer process separately, we introduced a parameter, a nuclear transfer score
      (NT score), which was calculated as the trans-gene expression after cytoplasmic
      microinjection divided by that after nuclear microinjection. RESULTS: As
      expected, the rank order of trans-gene expression after the transfection and
      cytoplasmic microinjection was NLS-mu > mu > PLL. However, the calculated NT
      scores were unexpectedly ranked as mu = NLS-mu > PLL, suggesting that mu, and not
      NLS(SV40), is responsible for the nuclear delivery of pDNA. In addition, confocal
      images of rhodamine-labeled pDNA indicated that pDNA condensed with mu and NLS-mu
      was delivered as a condensed form. In comparing the nuclear transcription, the
      rank order of trans-gene expression after nuclear microinjection was PLL = NLS-mu
      > mu, suggesting that intra-nuclear transcription is inhibited by efficient
      condensation by mu, and is avoided by the attachment of NLS(SV40). CONCLUSIONS:
      Collectively, NLS-mu, which consists of chimeric functions, is an excellent DNA
      condenser, and the process is based on mu-derived nuclear transfer and NLS(SV40)
      derived efficient intra-nuclear transcription.

PMID- 16285004
TI  - Sodium selenite protects against diabetes-induced alterations in the antioxidant
      defense system of the liver.
AB  - BACKGROUND: Free radical genesis of disorder is one of the major subjects of
      discussion in the explanation of pathological conditions. In this study, the
      effects of micro molar quantities of sodium selenite treatment on diabetes
      induced alterations in the antioxidant defense system were investigated. METHODS:
      Diabetes was induced by administration of streptozotocin (STZ, 50 mg/kg body
      weight) and both diabetic and control animals were treated with sodium selenite
      (5 micromol/kg/day) for 4 weeks. RESULTS: Our results have shown that induction
      of diabetes in the liver tissue of animals for 5 weeks resulted in decreased
      superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase
      (GSHPx) activities and concomitantly increased lipid peroxidation (LPO).
      CONCLUSION: Sodium selenite treatment of the diabetic rats resulted in almost
      full restoration of all the parameters mentioned above. Metallothionein, which is
      known to be one of the major antioxidants and a central protein in heavy metal
      regulation, is altered by diabetes, and sodium selenite treatment restored this
      alteration as well.

PMID- 16285005
TI  - Sonographic characteristics of linear nevus sebaceous sequence.
AB  - Linear nevus sebaceous is a hamartomatous lesion most commonly seen on the face
      and head of infants and diagnosed after birth. We describe a patient with
      sonographic findings of linear nevus sebaceous seen initially at 30 weeks'
      gestation. Other associated sonographic findings include macrocephaly and
      polyhydramnios. When associated with a midline soft tissue mass, these findings
      are highly suggestive of the presence of congenital linear nevus sebaceous
      sequence.

PMID- 16285006
TI  - The V617F JAK2 mutation and the myeloproliferative disorders.
AB  - The discovery this year of a single mutation in the Janus Kinase (JAK)-2 gene in
      a high percentage of cases of polycythaemia vera (PV), essential thrombocythaemia
      (ET) and myelofibrosis suggests that it maybe the underlying molecular mechanism
      for these disorders. Different approaches from the inhibition of the tyrosine
      kinase JAK2, widespread search for mutations in tyrosine kinases, and
      investigation of the short arm of chromosome 9 where JAK2 is located all led to
      the discovery of the V617F JAK2 mutation. Substitution of a valine for a
      phenylalanine destabilizes the JH2 domain of JAK2 causes loss of the auto
      inhibitory activity of this domain and explains some of the biological phenomena
      observed in patients with myeloproliferative disorders (MPD). The V617F JAK2
      mutation can be detected by PCR-direct sequencing using DNA from the granulocyte
      lineage or with increased sensitivity by the amplification refractory mutation
      system using DNA from unfractionated blood. Pyrosequencing assays can be used to
      quantitate allele ratios to accurately define homozygote and heterozygote status.
      This single mutation is widespread having been detected in related MPD and other
      haematological malignancies. This leads to a number of further questions about
      the role of this single mutation in the clinical pattern of disease.

PMID- 16285008
TI  - IL-12-independent Th1 polarization in human mononuclear cells infected with
      varicella-zoster virus.
AB  - T helper type 1 (Th1) cells perform a critical role in fighting intracellular
      organisms, and interleukin-12 (IL-12) is known to promote a Thl response. This
      study was conducted to identify whether an IL-12-independent Th1 reaction is
      induced by the varicella-zoster virus (VZV) in human beings. It was found that
      different intracellular microorganisms could induce IFNgamma but not IL-12
      production. Induction of IFNgamma production by VZV was associated with IFNalpha
      production and phosphorylation of both the signal transducer and activator of
      transcription-1 (STAT-1) and STAT-4 in lymphocytes. In contrast, Bacillus
      Calmette-Guerin (BCG) induced IL-12 production in association with STAT-4 but not
      STAT-1 activation. Anti-IFNalpha but not anti-IL-12 antibodies blocked the VZV
      induced Th1 polarization. A patient with an IL-12 receptor beta1 chain deficiency
      showed a normal VZV- but not a normal BCG-induced Th1 reaction, further
      supporting the concept of an IFNalpha-mediated, IL-12-independent Th1 reaction in
      response to certain intracellular infections. Identification of the early Th1
      polarization induced by IFNalpha versus IL-12 in response to specific viruses may
      enable the development of better therapeutic strategies tailored to different
      infections.

PMID- 16285007
TI  - Transient T cell accumulation in lymph nodes and sustained lymphopenia in mice
      treated with FTY720.
AB  - FTY720 (2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride) is an
      orally available immunomodulatory agent that induces severe peripheral blood
      lymphopenia. Most studies of these lymphopenic effects have been limited to short
      term exposure to FTY720. FTY720 alters the ability of lymphocytes to respond to
      sphingosine-1-phosphate (S1P) through S1P receptors, particularly S1P1. FTY720
      affects different leukocyte populations and their trafficking through major
      lymphoid organs. We show the dynamics of CD4 T, CD8 T, and B lymphocyte
      recirculation in all major lymphoid compartments during 21-day FTY720 treatment
      of normal C57BL/6 mice. Following a transient increase in peripheral lymph nodes
      and Peyer's patches, lymphocyte recirculation reaches a new steady state. Other
      lymphoid organs show transient changes in lymphocyte composition with various
      patterns. At 21 days of FTY720 treatment, total body lymphocyte content is
      reduced by 20% and blood lymphocytes by 80%. Modeling suggests that the new
      steady state is due to a combination of reduced naive lymphocyte release from the
      thymus and a transient reduction of lymphocyte egress from lymph nodes. Our data
      indicate that the commonly held belief that FTY720 blocks lymphocyte egress from
      lymph nodes cannot fully explain the lymphocyte dynamics observed with prolonged
      treatment.

PMID- 16285009
TI  - The Escherichia coli heat-labile enterotoxin induces apoptosis of immature
      lymphocytes in vivo via a glucocorticoid-dependent pathway.
AB  - Escherichia coli heat-labile enterotoxin (LT) exhibits a broad range of
      immunomodulatory activities, including the induction of lymphocyte-programmed
      cell death. However, the nature of the lymphoid populations sensitive to LT
      induced apoptosis and the mechanisms used by this toxin to promote such activity
      are still unclear. In this study, we demonstrate that LT induces in mice a rapid
      increase in the levels of circulating corticosterone, resulting in a dramatic
      induction of cell death of immature CD4+CD8+, B220+IgM- and IgM+IgD- T and B cell
      progenitors, respectively. Apoptosis of these cell populations is similar to that
      reported after experimental treatment with corticosteroids, it is inhibited by
      mifepristone, a glucocorticoid receptor antagonist, and does not occur in
      adrenalectomized animals. These results clearly indicate that endogenous
      glucocorticoids are the mediators of the LT-induced cell death, which involves
      Bcl-2-dependent apoptotic pathways. The LT-mediated programmed cell death
      requires systemic exposure and the enzymatic activity of LT, since a mutant
      devoid of any enzymatic activity have no pro-apoptotic effect at any dose tested.

PMID- 16285010
TI  - Dynamic regulation of FoxP3 expression controls the balance between CD4+ T cell
      activation and cell death.
AB  - The forkhead-family transcription factor FoxP3 is important for the development
      and function of CD4+CD25+ regulatory T cells. While the overall phenotypic
      effects of FoxP3 expression are evident, the mechanism by which FoxP3 regulates T
      cell activation is not well understood. CD4+ T cells from mice that express a
      FoxP3 Tg are refractory to TCR-mediated stimulation, failing to proliferate or
      produce cytokines, but possess suppressive activity towards normal T cells. In
      this report we show that these T cells express elevated levels of mRNA for pro
      apoptotic genes and undergo rapid apoptosis following stimulation. These T cells
      also display slower cell cycle transit following activation, suggesting that
      FoxP3 is capable of regulating the ability of T cells to respond to TCR-mediated
      activation. Lastly, we show that contrary to expected results, under Th1 or Th2
      driving conditions, CD4+ T cells from FoxP3 Tg mice differentiate into effector
      cells. Concomitant with differentiation is a loss of FoxP3 mRNA and protein.
      These data demonstrate that FoxP3 levels regulate T cell function, and that FoxP3
      itself is dynamically regulated during effector T cell differentiation.

PMID- 16285011
TI  - Heat denaturation, a simple method to improve the immunotherapeutic potential of
      allergens.
AB  - Allergen-specific immunotherapy (SIT) leads to a long-term amelioration of IgE-
      and Th2-mediated allergic diseases. However, SIT efficiency is low, with years of
      treatment along with frequent allergic side effects. The goal of this study was
      to reduce the side effects by destroying IgE-binding epitopes, i.e. by heat
      denaturation, while preserving the therapeutic effect. Mice were immunised with
      bee venom, birch pollen, grass pollen or cat hair allergens, or with ovalbumin.
      Heat-denatured allergens bound less IgE but enhanced Th1-dependent IgG2a
      production as measured by ELISA. The strong IgG2a antibody responses also
      prevented allergic anaphylaxis in mice, as measured by body temperature drop
      after a challenge with a high allergen dose. We found that optimal heat
      denaturation of allergens left a small proportion in the native conformation to
      sufficiently stimulate B cells, while non-B cell-mediated effects were probably
      amplified. The enhanced immunogenicity of heat-denatured allergens is likely
      explained by enhanced antigen presentation to T cells due to the particulate
      nature of heat-denatured proteins. This enables Th1 skewing of the immune
      response with strong production of IgG2a in mice. Therefore, heat-denaturation
      represents probably the simplest way to enhance the efficiency of SIT while
      reducing its side effects.

PMID- 16285013
TI  - Antibody-mediated signaling through PD-1 costimulates T cells and enhances CD28
      dependent proliferation.
AB  - Programmed death-1 (PD-1, CD279) is a molecule expressed on activated T, B and
      myeloid cells. The role of the interaction of PD-1 ligands (PD-L1 and PD-L2) with
      PD-1 receptor and the type of signals (costimulatory or inhibitory) that are
      delivered is a subject of intense debate. Our study has characterized two
      monoclonal antibodies (mAb) against murine PD-1, termed clone 1H10 and clone
      4F10, that recognized different epitopes from that of anti-PD-1, clone J43. We
      showed that neither of them inhibited anti-CD3-mediated proliferation, but 1H10
      mAb induced direct T cell proliferation in the absence of any other stimulus.
      Moreover, PD-1 engagement with 1H10 mAb costimulated anti-CD3-mediated
      proliferation and enhanced anti-CD3/CD28 proliferation on both CD4+ and CD8+ T
      cells in the low range of anti-CD3 concentrations. Anti-PD-1-mediated
      proliferation induced with 1H10 mAb was also observed in vivo on CD4+ and CD8+ T
      cells, when CFSE-labeled splenocytes were adoptively transferred to irradiated
      syngeneic and allogeneic recipients. Overall, our data indicate that PD-1 might
      not only deliver negative signals to T cells upon interaction through one of its
      ligands, PD-L1 as reported, but also could costimulate T cells, suggesting a dual
      potential functional activity of the extracellular domains of this receptor.

PMID- 16285012
TI  - The effects of thymic selection on the range of T cell cross-reactivity.
AB  - Based on the results of a computational model of thymic selection, we propose a
      mechanism that produces the observed wide range of T cell cross-reactivity. The
      model suggests that the cross-reactivity of a T cell that survives thymic
      selection is correlated with its affinity for self peptides. In order to survive
      thymic selection, a T cell with low affinity for all self peptides expressed in
      the thymus must have high affinity for major histocompatibility complex (MHC),
      which makes it highly cross-reactive. A T cell with high affinity for any self
      peptide must have low MHC affinity to survive selection, which makes it highly
      specific for its cognate peptide. Our model predicts that (1) positive selection
      reduces by only 17% the number of T cells that can detect any given foreign
      peptide, even though it eliminates over 95% of pre-selection cells; (2) negative
      selection decreases the average cross-reactivity of the pre-selection repertoire
      by fivefold; and (3) T cells responding to foreign peptides similar to self
      peptides will have a lower average cross-reactivity than cells responding to
      epitopes dissimilar to self.

PMID- 16285014
TI  - Mast cells are required for optimal autoreactive T cell responses in a murine
      model of multiple sclerosis.
AB  - Once considered to be of sole importance in allergy and parasitic infections, the
      role of mast cells in other pathologic and protective immune responses is
      becoming increasingly evident. We previously demonstrated that mast cells
      contribute to the severity of EAE, the rodent model of multiple sclerosis. Here
      we show that one mode of mast cell action is through effects on the autoreactive
      T cell response. Early indices of both peripheral CD4 and CD8 T cell activation,
      including IFN-gamma production and increases in CD44 and CD11a expression, are
      attenuated in mast cell-deficient (W/Wv) mice after myelin oligodendrocyte
      glycoprotein(35-55) priming when compared to WT animals. Reduced infiltrates of
      activated T cells in the central nervous system are also observed. Importantly,
      selective repletion of the mast cell compartment restores most T cell responses
      in the lymph nodes and the central nervous system, correlating with
      reconstitution of severe disease. The adoptive transfer of WT-derived
      encephalitogenic T cells results in significantly less severe disease in W/Wv
      recipients, indicating that mast cells also exert potent effects after the
      initial T cell response is generated. Our data provide the first in vivo evidence
      that mast cells can significantly influence T cell responses and suggest that
      mast cells exacerbate disease during both the inductive and effector phases.

PMID- 16285015
TI  - Glucocorticoid-induced TNFR family-related protein (GITR) activation exacerbates
      murine asthma and collagen-induced arthritis.
AB  - Glucocorticoid-induced TNFR family-related protein (GITR) is expressed at low
      levels on resting T cells, B cells and macrophages but at high levels on
      regulatory T cells (Treg). Although GITR expression is up-regulated on CD4+
      effector cells upon activation, the role of GITR in Th1 and Th2 cell development
      is unclear. We report here that activation of GITR signalling by anti-GITR
      antibody markedly enhanced the induction of both Th1 and Th2 cytokine production
      by naive CD4+CD25- T cells. Consistent with this observation, anti-GITR antibody
      significantly enhanced the expression of the key Th1 (T-bet) and Th2 (GATA3)
      transcription factors in vitro. Administration of anti-GITR mAb in a murine model
      of arthritis significantly exacerbated the severity and onset of joint
      inflammation with elevated production of TNF-alpha, IFN-gamma, IL-5, and collagen
      specific IgG1. Administration of anti-GITR mAb also significantly exacerbated
      murine allergic airways inflammation with elevated production of OVA-specific IFN
      gamma, IL-2, IL-4, IL-5, and IgE. Finally, we demonstrated that adoptive transfer
      of CD4+GITR+ T cells effectively abolished airway inflammation induced in SCID
      mice reconstituted with CD4+GITR- T cells. Our results therefore provide direct
      evidence that GITR can modulate both Th1- and Th2-mediated inflammatory diseases,
      and may be a potential target for therapeutic intervention.

PMID- 16285016
TI  - Metopic suture in fetuses with holoprosencephaly at 11 + 0 to 13 + 6 weeks of
      gestation.
AB  - OBJECTIVE: To investigate the development of the metopic suture in fetuses with
      holoprosencephaly at 11 + 0 to 13 + 6 weeks of gestation. METHODS: Three
      dimensional (3D) ultrasound was used to measure the height and gap between the
      frontal bones in 200 normal fetuses and in nine fetuses with holoprosencephaly at
      11 + 0 to 13 + 6 (median, 12) weeks of gestation. RESULTS: In the 200 normal
      fetuses, the height of the frontal bones increased significantly with gestation
      from a mean of 2.5 mm (5(th) and 95(th) centiles: 1.9 mm and 3.3 mm) at 11 weeks
      to 6.1 mm (5(th) and 95(th) centiles: 4.6 mm and 8.1 mm) at 13 + 6 weeks. The gap
      between the two frontal bones did not change significantly with gestation (mean:
      1.5 mm; 5(th) centile: 1.0 mm; 95(th) centile: 2.0 mm). In fetuses with
      holoprosencephaly, the height of the frontal bones was significantly larger (mean
      difference, 5.6 SDs; range, 3.9-7.7 SDs; P < 0.0001) and the gap was
      significantly smaller (mean 0.2 mm, range 0-0.8 mm; P < 0.0001) than those in
      normal fetuses. CONCLUSIONS: Holoprosencephaly is associated with an accelerated
      development of the frontal bones and premature closure of the metopic suture.

PMID- 16285017
TI  - Application of combined high-performance thin-layer chromatography immunostaining
      and nanoelectrospray ionization quadrupole time-of-flight tandem mass
      spectrometry to the structural characterization of high- and low-affinity binding
      ligands of Shiga toxin 1.
AB  - Shiga toxin 1 (Stx1) represents an AB5 toxin produced by enterohemorrhagic
      Escherichia coli, which cause gastrointestinal diseases in humans that are often
      followed by potentially fatal systemic complications, such as acute
      encephalopathy and hemolytic uremic syndrome. The expression of the preferential
      Stx1 receptor, Gb3Cer/CD77 (Gal alpha1-4Gal beta1-4Glc beta1-1Cer), is one of the
      primary determinants of susceptibility to tissue injury. Due to the clinical
      importance of this life-threatening toxin, a combined strategy of preparative
      high-performance thin-layer chromatography (HPTLC) overlay assay and mass
      spectrometry was developed for the detection and structural characterization of
      Stx1-binding glycosphingolipids (GSLs). A preparation of neutral GSLs from human
      erythrocytes, comprising 21.4% and 59.1% of the high- and low-affinity Stx1
      binding ligands Gb3Cer/CD77 and Gb4Cer, respectively, was separated on silica gel
      precoated HPTLC plates and probed for the presence of Stx1 receptors. Stx1
      positive on the one hand and anti-Gb3Cer/CD77 and anti-Gb4Cer antibody positive
      bands from parallel reference runs on the other hand were extracted with
      chloroform/methanol/water (30/60/8, v/v/v). These crude extracts were used
      without any further purification for a detailed structural analysis by
      nanoelectrospray ionization quadrupole time-of-flight mass spectrometry (nanoESI
      QTOF-MS) in the negative ion mode. In all extracts investigated, neutral GSLs
      were detected as singly charged deprotonated molecular ions, [M-H]-, and neither
      buffer-derived salt adducts nor coextracted contaminants from the overlay assay
      procedure or the silica gel layer were observed. For the structural
      characterization of Stx1- and antibody-binding GSLs low-energy collision-induced
      dissociation (CID) was applied to high and low abundant receptor species of the
      crude extracts. All MS/MS spectra obtained contained full series of Y-type ions,
      B-type ions and additional ions generated by ring cleavages of the sugar moiety.
      Only analytical quantities in the microgram scale of a single GSL species within
      the complex GSL mixture were required for the structural MS characterization of
      Stx1 ligands as Gb3Cer/CD77 and Gb4Cer. This effective combined HPTLC/MS
      procedure offers a broad range of applications, not only for toxins of bacterial
      origin, but also for any GSL-binding agents such as plant-derived lectins or
      human proteins with yet unknown binding specificities.

PMID- 16285018
TI  - Mass spectrometric studies of the formation and reactivity of trans
      [PtCl2(Am)(piperidinopiperidine)] x HCl complexes with ubiquitin.
AB  - trans-[PtCl2(Am)(pip-pip)] x HCl complexes, where Am = ammine, methylamine and
      dimethylamine, react with ubiquitin to form 1:1 covalent adducts. The platinum
      complexes bind exclusively to Met1 of ubiquitin forming trans-[PtCl(S-Met1
      Ub)(Am)(pip-pip)] adducts. These adducts are reactive towards nucleophiles and
      react with deoxyguanosine (dGMP) to form the ternary trans-[Pt(dGMP)(S-Met1-Ub)
      (Am)(pip-pip)] complex which is stable in water and even in the presence of
      excess glutathione (GSH). Reaction of trans-[PtCl(S-Met1-Ub)(Am)(pip-pip)] with
      GSH resulted in the rapid formation of the ternary complex trans-[Pt(GS)(S-Met1
      Ub)(Am)(pip-pip)] which was not stable and slowly lost the platinum moiety; after
      7 days the platinum moiety was completely removed and the native ubiquitin was
      regenerated.

PMID- 16285019
TI  - Asymmetric synthesis of N-protected chiral 1-aminoalkylphosphonic acids and
      synthesis of side chain-functionalized depsiphosphonopeptides.
AB  - Optically active 1-aminoalkylphosphonic acid derivatives were synthesized in
      moderate yields and optical purities via Mannich-type reactions of benzyl
      carbamate, aldehydes, and optically pure chlorophosphites. Side chain
      functionalized depsiphosphonopeptides were also prepared in satisfactory yields
      directly from one-pot reactions of benzyl carbamate, aldehydes, and diethyl (R,R)
      2-chloro-1,3,2-dioxaphospholane-4,5-dicarboxylate.

PMID- 16285020
TI  - Development of a gas chromatographic/mass spectrometric method to quantify R(-)
      apomorphine, R(-)-apocodeine and R(-)-norapomorphine in human plasma and urine.
AB  - A method was developed and validated for the analysis of R(-)-apomorphine, (R-)
      apocodeine and R(-)-norapomorphine in human plasma and urine with N
      propylnorapomorphine as internal standard using gas chromatography/mass
      spectrometry (GC/MS) and single-ion monitoring after a single liquid-liquid
      extraction and silylation of compounds. The quantification limits were 1 ng/ml
      for apomorphine and apocodeine and 25 ng/ml for norapomorphine. Calibration
      curves were linear, within the range 1-100 ng/ml. Variation in intraday and
      interday precision was below 10%. This method was applied to study apomorphine
      bioavailability in nine patients with Parkinson's disease before and after
      coadministration of a catechol-O-methyl transferase inhibitor.

PMID- 16285021
TI  - Limenin, a defensin-like peptide with multiple exploitable activities from shelf
      beans.
AB  - From the seeds of the shelf bean, an antifungal peptide with a molecular mass of
      6.5 kDa was isolated. The isolation procedure comprised affinity chromatography
      on Affi-gel blue gel, ion exchange chromatography on Mono S, and gel filtration
      on Superdex 75. The peptide was adsorbed on Affi-gel blue gel and Mono S. It
      potently suppressed mycelial growth in Botrytis cinerea, Fusarium oxysporum, and
      Mycosphaerella arachidicola with an IC(50) of 2.9, 2.1, and 0.34 microM,
      respectively. It exerted antibacterial activity toward several bacterial species
      with an IC(50) approximating 100 microM. [Methyl-(3)H]-thymidine incorporation
      into isolated mouse splenocytes was stimulated. [Methyl-(3)H]-thymidine
      incorporation into M1 (myeloma) and L1210 (leukemia) cells was inhibited. The
      peptide reduced the activity of HIV-1 reverse transcriptase and also inhibited
      translation in a cell-free rabbit reticulocyte lysate system.

PMID- 16285022
TI  - Mass spectrometric investigation of Maltacines E1a and E1b--two members of the
      Maltacine family of peptide antibiotics.
AB  - We have recently described the discovery of the Maltacines--a new family of
      cyclic peptide antibiotics from Bacillus subtilis. In this paper the mass
      spectrometric characterisation of two of the members is reported. A
      chemoselective ring opening with base to give the linear peptides was necessary
      before mass spectrometric characterisation could be performed. MS(n) of the
      singly and doubly charged protonated molecules gave uninterrupted series of Bn
      and Y''n ions that allowed determination of the amino acid sequence. By using a
      combination of derivatisation with phenylisothiocyanate (PITC), high-resolution
      mass spectrometry and H/D exchange, the identities of three unknown residues were
      determined. The nature and position of the cyclic structure were disclosed by a
      chemoselective ring opening with Na 18OH and it was found to be a lactone formed
      between a hydroxyl of residue number 4 and the C-terminal amino acid number 12.
      Peptides with different combinations of P/Q and P/K at the N-terminus were
      synthesised to verify the sequence of the N-terminal B2 ion. The structure of the
      two peptides is proposed to be: E1a: cyclo-4,12(P-Q-Y-Adip-V-E-T-Y-Orn-S-Y-I-OH)
      and E1b: cyclo-4,12(P-Q-Y-Adip-V-E-T-Y-K-S-Y-I-OH). Adip = (2-amino-4,5
      dihydroxypentanoic acid).

PMID- 16285023
TI  - Analogues of oxytocin antagonists bearing a ureido group in the amino acid side
      chain at position 4 or 5.
AB  - Substitution of the side chain carboxamido group at position 4 in the potent
      oxytocin antagonist (OTA) [ThiaPmp(1), D-Trp(2), Cys(6), Arg(8)]-OT, PA, in which
      ThiaPmp = beta,beta-(3-thiapentamethylene)-beta-mercaptopropionic acid, led to
      [Orn(Car)(4)]-PA, ([Cit(4)]-PA), which had uterotonic antagonistic activity equal
      to that of PA. The same modification at position 5, leading to [Cit(5)]-PA,
      resulted in antagonistic potency more than 10 times lower than that of PA. This
      paper also describes the same substitutions introduced in the highly potent OTA
      [Pen(6)]-PA (antioxytocic in vitro pA(2) = 8.72). Analogues of the general
      formula [U(4)-X(5)-Pen(6)]-PA, in which U = Lys, Orn, Dab, Dap or X = Orn, Dab or
      Dap, were synthesized by SPPS. Each of these analogues was carbamoylated by
      treatment with KCNO in DMF-H(2)O, yielding the corresponding U(Car)(4) or
      X(Car)(5) derivatives. In the uterotonic assay, the substitution with the ureido
      group at Gln(4) results in retention of high antagonistic potency, albeit
      somewhat lower than that of PA, e.g. [Orn(Car)(4), Pen(6)]-PA and [Dab(Car)(4),
      Pen(6)]-PA having pA(2) = 8.52 and pA(2) = 8.42 respectively. In the pressor
      assay, [Lys(Car)(4), Pen(6)]-PA and [Dab(Car)(4), Pen(6)]-PA were somewhat weaker
      antagonists of arginine vasopressin than [Pen(6)]-PA; [Dap(Car)(4), Pen(6)]-PA
      showed only a faint trace of pressor agonistic activity. The substitution with
      the ureido group at position 5 leads to a significant loss of OTA potency in the
      in vitro uterotonic assay. The [Orn(Car)(5), Pen(6)]-PA was the most potent of
      the series (pA(2) = 8.05). An interesting finding is that [Dap(Car)(5), Pen(6)]
      PA is equipotent with its precursor [Dap(5), Pen(6)]-PA (potency in the
      uterotonic test in vitro, pA(2) = 7.71 and pA(2) = 7.68, respectively).
      Furthermore, neither [Dap(5), Pen(6)]-PA nor [Dap(5), Pen(6), Gly(9)]-PA
      exhibited activity in the antidiuretic or pressor assays. Although these last two
      analogues show some decrease in antioxytocin potency, they behave as pure
      oxytocin antagonists, which makes them attractive candidates for further studies
      on the development of potent and specific OTAs.

PMID- 16285024
TI  - Synthetic, site-specific biotinylated analogs of human MCP-1.
AB  - Human monocyte chemoattractant protein 1 (MCP-1, CCL2) is a 8.6-kDa protein that
      has been implicated in a number of diseases including atherosclerosis, rheumatoid
      arthritis, chronic obstructive pulmonary disease and cancer. As part of a program
      to identify antibodies against MCP-1, we synthesized site-specific, biotinylated
      human MCP-1 analogs to be used for panning of an antibody phage display library.
      In contrast to material obtained from random biotinylation, the site-specific
      biotinylated analogs were homogeneous and retained full activity.

PMID- 16285025
TI  - Revisited and large-scale synthesis and purification of the mutated and wild type
      neu/erbB-2 membrane-spanning segment.
AB  - Solid-phase syntheses of the hydrophobic peptides Neu(TM35)
      ((1)EQRASPVTFIIATVVGVLLFLILVVVVGILIKRRR(35)) and Neu*(TM35)
      ((1)EQRASPVTFIIATVEGVLLFLILVVVVGILIKRRR(35)), corresponding to the native and
      mutated (V15E) transmembrane domain of the neu/erbB-2 tyrosine kinase receptor,
      respectively, were accomplished using Fmoc chemistry. The use of a new resin and
      cleavage and purification conditions led to large increases in yields and peptide
      purity. Two (15)N-labelled versions of both wild type and mutated peptides were
      also synthesized. Approximately 20-40 mg of peptide was obtained using a small
      scale synthesis, whereas ca 100 mg of pure peptide was collected on a medium
      scale. Peptide purity, as monitored by HPLC and mass spectrometry, ranged from 95
      to 98% for the six peptides synthesized. Secondary structure as determined by UV
      circular dichroism (CD) in trifluoroethanol (TFE) showed ca 74% alpha-helical
      content for the native peptide and ca 63% for that bearing the mutation.
      Secondary structure of Neu(TM35) was retained in DMPC
      (dimyristoylphosphatidylcholine)/DCPC (dicaproylphosphatidylcholine) membrane
      bicelles, and evidences for dimers/oligomers in the lipid bilayer were found.

PMID- 16285026
TI  - Protein interactions within calcium release units of muscle.

PMID- 16285027
TI  - Calcium regulation of single cardiac ryanodine receptor channels.

PMID- 16285028
TI  - Molecular studies in heart hypertrophy during pregnancy.

PMID- 16285029
TI  - Transcriptional regulation of sarcoplasmic reticulum Ca(2+)-ATPase and
      calsequestrin genes in cardiac myocytes.

PMID- 16285030
TI  - On the mechanism of myogenic tone in small arteries.

PMID- 16285031
TI  - Is infection a component of atherosclerosis?

PMID- 16285032
TI  - Emerging trends in combinations of gefitinib and cytotoxic agents: new
      opportunities.

PMID- 16285033
TI  - Concurrent radio-chemotherapy combination in patients with advanced head and neck
      squamous cell carcinoma.

PMID- 16285034
TI  - Case report: severe heat stroke with multiple organ dysfunction - a novel
      intravascular treatment approach.
AB  - INTRODUCTION: We report the case of a patient who developed a severe post
      exertional heat stroke with consecutive multiple organ dysfunction resistant to
      conventional antipyretic treatment, necessitating the use of a novel endovascular
      device to combat hyperthermia and maintain normothermia. METHODS: A 38-year-old
      male suffering from severe heat stroke with predominant signs and symptoms of
      encephalopathy requiring acute admission to an intensive care unit, was admitted
      to a ten-bed neurological intensive care unit of a tertiary care hospital. The
      patient developed consecutive multiple organ dysfunction with rhabdomyolysis, and
      hepatic and respiratory failure. Temperature elevation was resistant to
      conventional treatment measures. Aggressive intensive care treatment included
      forced diuresis and endovascular cooling to combat hyperthermia and maintain
      normothermia. RESULTS: Analyses of serum revealed elevation of proinflammatory
      cytokines (TNF alpha, IL-6), cytokines (IL-2R), anti-inflammatory cytokines (IL
      4) and chemokines (IL-8) as well as signs of rhabdomyolysis and hepatic failure.
      Aggressive intensive care treatment as forced diuresis and endovascular cooling
      (CoolGard and CoolLine) to combat hyperthermia and maintain normothermia were
      used successfully to treat this severe heat stroke. CONCLUSION: In this case of
      severe heat stroke, presenting with multiple organ dysfunction and elevation of
      cytokines and chemokines, which was resistant to conventional cooling therapies,
      endovascular cooling may have contributed significantly to the reduction of body
      temperature and, possibly, avoided a fatal result.

PMID- 16285035
TI  - Proceedings of the Third International Symposium Biochemical and Physiological
      Aspects of Muscle Research. May 6-9, 2003. Mexico City, Mexico.

PMID- 16285037
TI  - [IX National Conference of Gynecology. Bansko, February 24-26, 2005].

PMID- 16285036
TI  - Protein detection goes down to the wire.

PMID- 16285038
TI  - [VI National Conference of Obstetrics and Gynecology. Sandanski, November 19-20,
      2004].

PMID- 16285039
TI  - [Active immunotherapy in patients with hematologic and solid neoplasms].

PMID- 16285040
TI  - [Value of inhibition of signal transduction and epigenetic therapy concepts in
      cancer therapy].

PMID- 16285041
TI  - Use of GnRHa to induce ovulation in GnRH antagonist cycles.

PMID- 16285042
TI  - Neutralizing effects of an anti-vascular endothelial growth factor antibody on
      tooth movement.
AB  - Our recent studies demonstrated that local administration of recombinant human
      vascular endothelial growth factor (rhVEGF) during experimental tooth movement
      enhanced the number of osteoclasts and the rate of tooth movement. The purpose of
      this study was to examine the effect of anti-VEGF polyclonal antibody on
      osteoclastic differentiation, the amount of tooth movement, and the degree of
      tooth relapse in 30-day-old mice. First, these mice were subjected to various
      doses of anti-VEGF polyclonal antibody, with tooth movement for three days. In
      the next study, daily injections of 10-microg antibody were administered for 18
      days during the experimental tooth movement. The amount of tooth movement was
      measured as in our previous study. Furthermore, in the third study, we
      administered daily injection of 10-microg antibody and measured tooth relapse
      after the experimental tooth movement for 45 days. The osteoclasts number in 10-
      and 50-microg antibody two-time injection group was significantly smaller than
      that in the controls (P < .05). The number of osteoclasts was decreased more
      substantially by daily injection of 10-microg antibody, showing more significant
      differences from the controls (P < .01). The amount of tooth movement was
      significantly less in the experimental group than in the controls on days 15 and
      18 (P < .05). Furthermore, the amount of relapse in the experimental group was
      significantly less than that in the controls on days 9 and 11 after removal of
      the appliance (P < .05). These results show that the treatment of anti-VEGF
      polyclonal antibody markedly reduced the osteoclasts number and inhibited the
      amount of tooth movement and relapse of moved teeth.

PMID- 16285043
TI  - Shear bond strength of orthodontic brackets with newly developed antibacterial
      self-etch adhesive.
AB  - Because the enamel adjacent to brackets may be affected by microorganisms, an
      antibacterial adhesive may be a useful choice to prevent and reduce
      demineralization. The purpose of this in vitro study was to determine the (1)
      shear bond strength of a self-etch and an antibacterial self-etch adhesive for
      orthodontic metal brackets and (2) bond failure interface of a self-etch and an
      antibacterial self-etch adhesive using a modified adhesive remnant index (ARI).
      Twenty-four defect-free premolars were randomly assigned into two groups. The
      teeth received the following treatments-group 1: Transbond Plus Self-Etching
      Primer + Transbond XT; group 2: antibacterial dentin bonding system (ABF) +
      Transbond XT. All samples were stored in deionized water at 37 degrees C for 48
      hours. Shear debonding tests were performed at a crosshead speed of five mm/min.
      The results in megapascals were (median, minimum, maximum) group 1: 8.53, 4.59,
      12.63; group 2: 9.79, 4.01, 22.10, respectively. Mann-Whitney test revealed that
      the difference between the groups was not statistically significant (P = .2, P >
      .05). Failed brackets were examined by an optical microscope at 16x magnification
      to determine the bond failure interface using a modified ARI. The predominant
      mode of failure for both groups was at the bracket-adhesive interface. ABF may
      have sufficient mechanical properties and also an antibacterial effect that makes
      it a good choice for orthodontic bonding.

PMID- 16285044
TI  - Shear bond strength of metallic orthodontic brackets bonded to enamel prepared
      with Self-Etching Primer.
AB  - The aim of this study was to determine the shear bond strength of different
      composites and to determine the adhesive remnant index (ARI) of metallic brackets
      bonded to enamel prepared with Transbond Plus Self-Etching Primer (TPSEP). Forty
      human premolars were divided into four equal groups. In group 1 (control), the
      Transbond XT was conventionally used. In groups 2-4, the TPSEP was used before
      bonding with Transbond XT, Z-100, and Concise Orthodontic, respectively. After
      the bonding, the samples were stored in distilled water at 37 degrees C for 24
      hours. The brackets were debonded using a universal testing machine at a
      crosshead speed of 0.5 mm/ min. The shear bond strength (MPa) for group 1
      (control), group 2 (TPSEP + Transbond XT), group 3 (TPSEP + Z-100), and group 4
      (TPSEP + Concise Orthodontic) were of 6.43, 4.61, 4.74, and 0.02, respectively.
      Group 1 was statistically superior to other groups (P < .05), but there was no
      statistically significant difference between groups 2 and 3 (P > .05), although
      both were statistically superior to group 4 (P < .05). According to the ARI
      evaluation, most of the failures involved the bracket/composite interface (groups
      1 and 2) as well as the enamel/composite interface (groups 3 and 4). The
      Transbond XT conventionally bonded showed better adhesion results than Transbond
      XT, Z-100, and Concise Orthodontic after using Transbond Plus Self-Etching
      Primer.

PMID- 16285045
TI  - For family members only.

PMID- 16285046
TI  - Aging and depression. Not a matched set.

PMID- 16285047
TI  - Cooking from the diabetes food pyramid. Grains, beans, and starchy vegetables.

PMID- 16285048
TI  - Long-term care insurance.

PMID- 16285049
TI  - Finer diner dining.

PMID- 16285050
TI  - Eating right for healthy kidneys.

PMID- 16285051
TI  - Blood glucose monitoring update.

PMID- 16285052
TI  - Dealing with constipation.

PMID- 16285053
TI  - Diabetes quiz.  How well do you know your diabetes vocabulary?

PMID- 16285054
TI  - Exercising with an insulin pump.

PMID- 16285055
TI  - Supermarket smarts. Wild game and specialty meats.

PMID- 16285057
TI  - Disability income insurance.

PMID- 16285056
TI  - For parents. Getting ready for college.

PMID- 16285058
TI  - Overcoming binge eating disorder.

PMID- 16285060
TI  - Cooking from the diabetes food pyramid. Fruit.

PMID- 16285059
TI  - Lowering your risk of cardiovascular disease.

PMID- 16285062
TI  - Relaxation techniques for stressful times.

PMID- 16285061
TI  - Analyze this! Interpreting your monitoring log.

PMID- 16285063
TI  - Power cleaning your teeth.

PMID- 16285064
TI  - Sleep debt. A wake-up call.

PMID- 16285066
TI  - Diabetes quiz. How much do you know about exercising safely?

PMID- 16285065
TI  - Caring for your feet.

PMID- 16285067
TI  - Supermarket smarts. Bread mixes and doughs.

PMID- 16285068
TI  - For parents. Playing soccer. What's your game plan?

PMID- 16285069
TI  - Aripiprazole: new drug. Just another neuroleptic.
AB  - (1) Neuroleptics are the standard treatment for schizophrenia. The first drugs of
      this class, such as haloperidol, were marketed nearly 50 years ago, and
      neuroleptics released over the past 15 last years have provided no major advance.
      (2) Aripiprazole is a new neuroleptic licensed for the treatment of
      schizophrenia. (3) Five double-blind placebo-controlled trials lasting 4 to 6
      weeks showed that aripiprazole was a little more effective than placebo at daily
      doses of 10 mg to 30 mg, without a clear dose-response relationship. Based on the
      least demanding definition of "treatment response" (a 30% reduction in the PANSS
      global score), less than 50% of patients responded to aripiprazole. (4) In a
      double-blind trial lasting 6 months, aripiprazole 15 mg/day was more effective
      than placebo in preventing acute relapses of schizophrenia (34% versus 57%), but
      the clinical relevance of the combined endpoint used to define relapse is
      unclear. (5) The only double-blind comparison versus another neuroleptic
      (haloperidol) involved two trials that were pooled for analysis. Haloperidol was
      provided at a moderate dose (10 mg/day). These trials were designed to
      demonstrate the superiority of high-dose aripiprazole (30 mg/day), but failed to
      do so. The proportion of patients who "responded" during an acute episode, based
      on the least stringent definition, was about 70% in both groups. In both groups,
      response persisted in approximately three-quarters of patients. (6) Aripiprazole
      exhibits the adverse effects classically seen with neuroleptics. In clinical
      trials, daily doses of aripiprazole, ranging from 15 mg to 30 mg, provoked fewer
      extrapyramidal disorders than haloperidol 10 mg/day. In contrast, there was no
      difference in the frequency of extrapyramidal disorders with aripiprazole 20 or
      30 mg/day and risperidone (6 mg). Aripiprazole has no proven advantage over
      haloperidol in terms of the risk of tardive dyskinesia. One trial showed no
      difference between aripiprazole and olanzapine in the risk of diabetes. Weight
      gain appears to be comparable with aripiprazole and haloperidol. Aripiprazole
      provoked postural hypotension and neuroleptic malignant syndrome, but the precise
      risk relative to other neuroleptics has not been documented. Supra-therapeutic
      doses of aripiprazole cause dose-dependent QT prolongation. (7) Increased
      mortality was seen in elderly patients treated with aripiprazole. (8) Animal
      studies have shown retinal degeneration in rats and biliary lithiasis in monkeys.
      These adverse effects have not been observed in clinical trials, but they have
      not been specifically assessed in humans. (9) Animal studies raised the
      possibility of fetal toxicity and teratogenicity. (10) The aripiprazole dose must
      be either halved or doubled during co-administration with inhibitors or inducers
      of cytochrome P450 isoenzymes CYP 3A4 and CYP 2D6. (11) In practice, there are
      too many unanswered questions to recommend aripiprazole for patients with
      schizophrenia.

PMID- 16285070
TI  - Miglustat: new drug. In type 1 Gaucher's disease : a slight benefit after
      imiglucerase therapy.
AB  - (1) For patients with type 1 Gaucher's disease the standard treatment is
      imiglucerase enzyme replacement therapy, provided in fortnightly intravenous
      infusions. (2) Miglustat inhibits the synthesis of glucosyl-ceramide, the
      cerebroside that accumulates in Gaucher's disease. Miglustat is now licensed for
      oral therapy in patients with mild to moderate type 1 Gaucher's disease and who
      cannot take imiglucerase, regardless of the reason. (3) The evaluation data we
      managed to gather (see literature search) includes data from three trials
      involving a total of 82 patients. One of these trials compared miglustat with
      ongoing imiglucerase therapy. Miglustat slightly reduced the size of the liver
      and spleen, and slightly increased the haemoglobin level and platelet count after
      18 months. The impact of these effects is unknown, especially on bone disorders.
      In patients with previous response to imiglucerase, miglustat has not been found
      to maintain clinical effects in the longer term. (4) Miglustat has many adverse
      effects, some of which occur very frequently, such as diarrhea (86%), weight loss
      (64%), peripheral neuropathies (19%), tremor (29%), and cognitive disorders.
      Animal studies suggest a risk of reproductive toxicity. (5) In practice,
      miglustat therapy offers minimal benefits for the few patients who cannot use
      imiglucerase. The potential advantages of miglustat therapy relative to purely
      symptomatic treatment must be carefully weighed in individual patients.

PMID- 16285071
TI  - Ibritumomab: new drug. Interesting concept, disappointing in practice.
AB  - (1) First-line standard chemotherapy for follicular non-Hodgkin's lymphoma is
      based on alkylating agents. For patients who relapse, rituximab, a monoclonal
      antibody targeting CD20 receptors on tumour cells, induces remissions lasting at
      least 9 months in about 50% of cases. However, the infusions are often poorly
      tolerated and reactions can be severe. (2) Ibritumomab is a monoclonal antibody
      similar to rituximab. It is not in itself cytotoxic. Yttrium-90-radiolabeled
      ibritumomab has been licensed in the EU since 2004 for local tumour radiotherapy,
      administered shortly after rituximab therapy. It is approved as a third-line
      treatment for follicular lymphoma, after rituximab failure. (3) The only
      available comparative trial, lasting 4 years, involved 143 patients who were
      treated either with rituximab followed by radiolabeled ibritumomab, or with
      rituximab alone. The sequential treatment yielded more tumour responses but the
      time to lymphoma progression and clinical outcomes did not differ between the two
      treatment groups. (4) In a non comparative trial about half the patients in whom
      rituximab had failed responded to rituximab + radiolabeled ibritumomab, but
      lymphoma progression occurred after a median of only 7 months. (5) Patients who
      receive sequential therapy with rituximab + ibritumomab are exposed to the
      adverse effects of rituximab plus supplementary gastrointestinal, respiratory,
      haematological and infectious risks, mainly due to persistent myelosuppression.
      (6) The radiation hazard for the patient (irradiation of healthy organs) and for
      the environment appears to be limited, because of the short reach of beta
      particle emission (5 mm) and the short half-life of yttrium 90 (2.7 days). (7)
      Yttrium 90 radiolabeling requires special equipment and specialised personnel
      working in an approved centre, which can restrict access to treatment. (8)
      Radiolabeled ibritumomab appears to have a negative risk-benefit balance, and
      should only be used in clinical trials.

PMID- 16285072
TI  - Darbepoetin alfa: new indication/new dosage. No proven advantage in chemotherapy
      induced anaemia.
AB  - (1) Current treatments for anaemia in patients receiving cancer chemotherapy
      include blood transfusion and epoetin alfa and beta. These epoetins correct
      anaemia in 40% to 65% of patients and reduce the number of patients who require
      transfusions during the second and third months of treatment by 12-35% in
      absolute terms. (2) Darbepoetin alfa is slightly more glycosylated than epoetin
      alfa and beta. It is no more effective than these two drugs in chronic renal
      failure. Darbepoetin alfa is now approved for the treatment of anaemia in
      patients who are receiving chemotherapy for non myeloid malignancies. (3) Two
      placebo-controlled dose-finding studies and two placebo-controlled trials
      involving nearly 1000 patients in total have shown that darbepoetin alfa
      decreases the number of transfused patients by 17-25% in absolute terms, and that
      it probably reduces fatigue. However, one-quarter of patients receiving
      darbepoetin were nonetheless transfused. (4) In the absence of reliable
      comparisons, there is no firm evidence that darbepoetin alfa is more effective
      than other epoetins. (5) According to relatively imprecise company reports,
      darbepoetin alfa increased the risk of thromboembolic events during clinical
      trials (6% versus 3%), including pulmonary embolism (1.3% versus 0%); the company
      also states that darbepoetin alfa does not increase the risk of arterial
      hypertension, a classical effect of epoetin that is mentioned in the summary of
      product characteristics (SPC). Placebo-controlled trials and dose-finding studies
      show no impact on the outcome of cancer, but follow-up is limited and a negative
      effect cannot be ruled out. The company states that no cases of
      erythroblastopenia have occurred among more than 70 000 treated patients. (6)
      According to the SPC, darbepoetin alfa can be given once a week. However, the
      optimal epoetin dosing schedule is unknown. Epoetin therapy takes several weeks
      to correct anaemia, whereas transfusion is immediately effective. (7) In
      practice, darbepoetin alfa seems a little easier to administer than epoetin alfa
      or beta, but the advantages and disadvantages of these drugs as compared with
      blood transfusion are not entirely clear.

PMID- 16285073
TI  - Celecoxib still on the market: but for whose benefit?
AB  - (1) The cardiovascular risks associated with Cox-2 inhibitor therapy were
      confirmed in early 2005, and measures restricting the use of these drugs were
      taken in several countries. Yet celecoxib remains on the market. (2) Comparative
      trials versus other NSAIDs failed to show that celecoxib was any more effective
      for pain relief. And, following damning revelations that the CLASS study results
      had been manipulated, it became clear that celecoxib had no tangible advantage in
      terms of serious gastrointestinal complications. (3) An increase in Cox-2
      inhibitor prescriptions, primarily based on their reputation for better
      tolerability, led to an increase in the absolute number of cases of
      gastrointestinal haemorrhage. (4) A trial focusing on the prevention of
      colorectal polyps showed that cardiovascular events occurred two to three times
      more frequently with celecoxib than with placebo. Another trial showed no
      significant difference. (5) In a trial involving patients with Alzheimer's
      disease, overall mortality was higher with celecoxib than in the placebo group.
      The difference was similar to that observed in placebo-controlled trials of
      rofecoxib in Alzheimer's disease. (6) The celecoxib affair once again highlights
      certain failings of the American and European regulatory agencies: celecoxib is
      still on the market, exposing patients to risks associated with its use without
      providing any therapeutic advantage.

PMID- 16285074
TI  - Infliximab: lymphomas and severe hepatitis.

PMID- 16285075
TI  - Angiotensin II receptor antagonists and heart failure: angiotensin-converting
      enzyme inhibitors remain the first-line option.
AB  - (1) Some angiotensin-converting-enzyme inhibitors (ACE inhibitors) reduce
      mortality in patients with heart failure (captopril, enalapril, ramipril and
      trandolapril), and in patients with recent myocardial infarction and heart
      failure or marked left ventricular dysfunction (captopril, ramipril and
      trandolapril). (2) Angiotensin II receptor antagonists, otherwise known as
      angiotensin receptor blockers, have haemodynamic effects similar to ACE
      inhibitors, but differ in their mechanism of action and certain adverse effects.
      (3) Five clinical trials have evaluated angiotensin II receptor antagonists
      (candesartan, losartan and valsartan) in terms of their effect on mortality and
      on the risk of clinical deterioration in patients with symptomatic heart failure,
      but without severe renal failure, hyperkalemia or hypotension. In these trials,
      candesartan and valsartan were used at much higher doses than those recommended
      for the treatment of arterial hypertension. (4) In patients with heart failure
      who were not taking an angiotensin II receptor antagonist or an ACE inhibitor at
      enrollment, no significant difference was found between losartan and captopril in
      terms of mortality or the risk of clinical deterioration. (5) In patients with
      heart failure who had stopped taking an ACE inhibitor because of adverse effects,
      candesartan had no effect on mortality as compared with placebo, but it did
      reduce the risk of clinical deterioration (3 fewer hospitalisations per year per
      100 patients). However, candesartan was associated with adverse effects such as
      renal failure and hyperkalemia, especially in patients who had experienced these
      same adverse effects while taking an ACE inhibitor. (6) In patients with heart
      failure who were already taking an ACE inhibitor, adjunctive candesartan or
      valsartan treatment did not influence mortality in comparison to the addition of
      a placebo. Adding candesartan or valsartan reduced the risk of hospitalisation
      (between 1 and 3 fewer hospitalisations per year per 100 patients), but increased
      the risk of renal failure and hyperkalemia. (7) In patients with heart failure
      and incapacitating dyspnea despite ACE inhibitor + diuretic combination therapy,
      there are no trials comparing the addition of an angiotensin II receptor
      antagonist versus spironolactone. Adjunctive spironolactone therapy prevents 5 to
      6 deaths per year per 100 patients in this setting. (8) In patients with heart
      failure who do not have markedly altered cardiac contractility, candesartan
      appears to have no clinical advantages over placebo. (9) In some of these trials,
      mortality was higher with angiotensin II receptor antagonist therapy than with
      placebo among patients who were already taking a betablocker. (10) Two trials
      have compared an angiotensin II receptor antagonist with an ACE inhibitor in
      patients with recent myocardial infarction who had heart failure or an altered
      left ventricular ejection fraction, but who did not have hypotension or severe
      renal failure. However, there are no placebo-controlled randomised trials
      assessing the effects of angiotensin II receptor antagonists on mortality. (11)
      In patients with recent myocardial infarction, these trials showed no difference
      in mortality between angiotensin II receptor antagonist treatment (losartan or
      valsartan) and captopril. They did not rule out the possibility that these
      angiotensin II receptor antagonists are moderately less effective than captopril.
      Adding valsartan to ongoing captopril therapy did not reduce mortality or
      morbidity as compared with placebo, but did increase the risk of adverse effects.
      (12) Overall, these trials confirm the advantage of angiotensin II receptor
      antagonists over ACE inhibitors with respect to some adverse effects (cough, skin
      rash, etc.). However, the two drug classes share certain serious adverse effects
      such as hyperkalemia, renal failure and hypotension. In one trial, angioedema was
      less frequent with angiotensin II receptor antagonist therapy (one less case per
      500 patients).

PMID- 16285076
TI  - Insulin in type 2 diabetes: a useful alternative despite limited assessment based
      on surrogate endpoints.
AB  - (1) There are few clinical trials comparing combination therapy with a
      sulphonylurea and metformin after oral antidiabetic monotherapy fails to provide
      adequate glycaemic control. The UKPDS study suggested that this combination had a
      negative impact on mortality. (2) The assessment of insulin therapy in patients
      in whom oral antidiabetic therapy fails is based solely on surrogate endpoints:
      mainly HbA1c (glycated haemoglobin), bodyweight, and the frequency of
      hypoglycaemia. (3) In a comparative randomised trial involving patients whose
      glucose levels were no longer controlled by a sulphonylurea, the addition of
      metformin or a daily injection of insulin isophane (NPH) was similarly effective
      in reducing HbA1c levels. However, metformin caused less weight gain. (4) There
      are no randomised controlled trials comparing the addition of insulin versus a
      sulphonylurea when ongoing metformin monotherapy is inadequate. (5) Randomised
      comparative trials show that, when glycaemia is no longer controlled by a
      sulphonylurea plus metformin, adding a daily insulin injection is more effective
      in lowering HbA1c levels than the addition of acarbose and as effective as adding
      a glitazone. The adjunction of insulin appears to have a better risk-benefit
      balance than an oral three-drug regimen. (6) Several randomised controlled trials
      have shown that the addition of an oral antidiabetic to ongoing insulin therapy
      reduces HbA1c levels in patients with type 2 diabetes. The addition of metformin
      is also beneficial in terms of body weight changes. (7) Nine randomised
      controlled trials involving patients whose glycaemia was inadequately controlled
      by a sulphonylurea, alone or in combination with metformin, have compared the
      addition of a bedtime injection of insulin isophane versus replacement of the
      oral antidiabetics by several daily insulin injections. The two strategies had a
      similar impact on HbA1c (-1.5% to -2.5%), but patients experienced less weight
      gain when the oral antidiabetics were continued and a single insulin injection
      was added. (8) The few available comparative trials fail to show which oral
      treatment (a sulphonylurea, metformin, or a combination of the two) has the best
      risk-benefit balance when combined with a bedtime injection of insulin isophane.
      (9) Insulin isophane is the first-choice insulin for combination therapy with an
      oral antidiabetic. In comparative trials, when combined with an oral
      antidiabetic, insulin glargine was no more effective than insulin isophane in
      terms of HbA1c levels or weight gain. Insulin glargine seems to provoke less
      hypoglycaemia but, in the absence of adequate follow-up, its long-term adverse
      effects are not known. (10) When a bedtime insulin injection plus an oral
      antidiabetic fail to control hyperglycaemia, indirect comparisons support the use
      of several daily insulin injections plus metformin, or three injections of an
      ultrarapid insulin analogue plus a sulphonylurea.

PMID- 16285077
TI  - Euthanasia: a "kit" sold in Belgian pharmacies.
AB  - (1) In France, legislation adopted in 2005 recognises the right of dying patients
      to refuse further treatment, and the right of physicians to ease their suffering
      with treatments that, due to adverse effects, may shorten their life. Measures
      deliberately aimed at hastening death are forbidden. (2) In Belgium, medical
      euthanasia was decriminalised in 2002, and can now be carried out either in
      hospital or at home. Nearly 20 cases of euthanasia are reported per month in
      Belgium. (3) A Belgian pharmacy chain now markets a "euthanasia kit".

PMID- 16285078
TI  - [Some questions about history of medicine learning].

PMID- 16285079
TI  - [The 'feminine' in the history of medical didactics].
AB  - Women are present in the 'long' history of medicine both as patients and as
      healers specialising in curing and caring. The nowadays existing attempt to
      define a female specific medical knowledge (discussing, for instance, the quality
      of a supposed 'female' cultural and professional training; the role of women in
      medical research as well as in discussing bioethical subjects; the relationship
      between women-physicians and other medical professionals; the female approach to
      important bioethical issues such as euthanasy, 'therapeutical fury' for the
      incurable sick, female genital mutilations) is here analyzed in a broader
      historical context.

PMID- 16285080
TI  - [Medicine and university in Naples in the 17th and 18th centuries: a research
      project].
AB  - The teaching of medicine at Naples university in the 17th and early 18th
      centuries is somewhat difficult to reconstruct, due to the loss of archival
      evidence. The research project relies on student notes, conserved in Italian
      libraries and in the Wellcome Library for the History and Understanding of
      Medicine in London. The manuscript notes are likely to shed new light on the
      little known contents of the medical curricula, as well as contrasting the
      commonplace of a complete decline of universities as centers of scientific
      innovation and active debate in the 17th century in Italy.

PMID- 16285081
TI  - [History of orthopaedic teaching in Rome].
AB  - The article deals with the history of orthopedics in Rome University 'La
      Sapienza', since its beginning in the XVI century at the Roman Hospitals della
      Consolazione and S. Spirito in Saxia.

PMID- 16285083
TI  - [Recording instruments in the physiology of the late nineteenth century].
AB  - This paper aims at describing the revolution in sensorial physiology resulting
      from the introduction of electrical recording instruments such as the string
      galvanometer and especially the capillary electrometer by Edgar Douglas Adrian in
      Cambridge. The contributions in the field of vacuum-tube methods completed the
      development and the progress in the analysis of the action potential of nerve.

PMID- 16285082
TI  - Constructing clinical science.
AB  - Clinical practice became clinical science in the years 1720-1820. There were many
      reasons for this transformation. The discoveries by Santorio Santorio, William
      Harvey, Marcello Malpighi, Giovanni Alfonso Borelli, Lorenzo Bellini, Thomas
      Sydenham, Giovanni Maria Lancisi, were perceived by students who asked for
      changes in the medical curriculum. In 1761 Morgagni centered the study of
      diseases on morbid anatomy, a way to control at autopsy the validity of
      diagnosis. J.P. Frank who worked on public health and John Locke who supported a
      method of scientific reasoning based on asking questions were also instrumental
      for changes. Hospitals, formerly hospices for the poor, became places for curing
      and healing. Military hospitals represented models to be followed. In Vienna
      Marie Therese inaugurated the Allegemein Krankenhaus in 1785. In revolutionary
      France Fourcroy with the law Frimaire An III, 1794 gave a new rationale. Medicine
      and surgery were unified in the curriculum. Basic sciences were introduced.
      Dissection became compulsory, practical teaching became the rule. But it was with
      John Hunter, Domenico Cotugno and P. Joseph Desault that the great advancement
      was achieved. They were anatomists and therefore they made the knowledge of human
      body the core of medical curriculum. However experimentation on animals, as well
      as practical bedside teaching at the hospital also became important. Through
      their work hospitals and universities were associated in a common goal.

PMID- 16285084
TI  - [Epistemology and b-thalassemia].
AB  - In this work the author examines the epistemological pathway to the study,
      diagnosis and therapy of b-thalassemia, serious and very frequent genetic disease
      in the Italian and Sardinian population know to paediatricians since 1925. The
      author critically explores the historical approaches to the comprehension of the
      disease, the phenotype characteristics, firstly described in Italy in 1929, and
      its familiarity, also described from several authors in the same years. The
      frequency and the variability of the disease in the population were poorly
      understood, partly because haematology was still under development and partly for
      the presence in the patients and in the general population of confounding
      symptoms and diseases. The hereditary transmission according to Mendelian laws
      was applied only to the study of few phenotype characteristics, in the attempt to
      limit the familiar transmission from the long surviving patients. For over 50
      years the disease was considered lethal and there were not studies on the real
      efficacy of the available treatments.

PMID- 16285085
TI  - [The question of "Applied Sciences" in Italy, after the unification, and the
      contribution of Francesco Selmi to forensic medicine].
AB  - In the Italian intellectual outline of the second half of the XIX century
      Francesco Selmi stands out for his discoveries in organic and inorganic chemistry
      as well as in toxicology. He also addressed his efforts to promote the
      relationship between science and industry.

PMID- 16285086
TI  - [A new dimension for medical experience].
AB  - Didactic of medicine has changed dramatically over the past few years. A
      historical overview is necessary to educate young physicians through a better
      knowledge of the past of medical scientific research.

PMID- 16285087
TI  - [Giovanbattista da Monte (Montanus): father of modern clinical medicine].
AB  - The figure of Giovanbattista da Monte (1489-1551) is associated with the
      introduction of clinical teaching at the patient's beside, in 1543, at the San
      Francesco Hospital of Padua. In the XVI century, teaching was still based on the
      explanation and comment of the ancient authors and the educational programme was
      founded on theoretical aspects. The "practical" approach consisted of the
      treatment "ex cathedra" of diseases according to the various parts of the body,
      without observing the course of the pathological events with a direct
      confirmation at the patient's beside.To his merit, Da Monte established the
      practise of training students to gather the case history, to carry out an
      objective examination, and to closely examine disease phenomena with lessons at
      the bedside of the patient. Practical clinical training was thus introduced as
      the crucial moment in the formation of the physician.

PMID- 16285088
TI  - From splenic anemia in infancy to microcythemia. The Italian contribution to the
      description of the genetic bases of Thalassemia.
AB  - This article traces out part of the history of studies of the genetic bases of
      thalassemia carried out in Italy. In particular it illustrates the research and
      discussions that between the late 1920s and the second half of the 1940s led to
      the description of the genetic basis of beta-thalassemia. The article encountered
      by Italian research, explaining why, despite the large number of thalassemia
      cases and data collected for this disease, Italian researchers succeeded in
      demonstrating its Mendelian transmission only at the same time as the US
      researchers.

PMID- 16285090
TI  - [The transformation of medicine in post-Mao China].
AB  - The article regards the Chinese medicine and the transformation of psychiatry in
      the post-modern China. Politics health, in China's Republic brought about an
      improvement in the living standard of the people. Nowdays, after a period of
      isolation, both medicine and psychiatry, in China, have hit the same
      technological level than the western ones. However, because of cultural isolation
      and the new market economy, there are some theoretical and clinical
      contradictions. These have caused a slackening in the research and the living
      standard of the people.

PMID- 16285089
TI  - [Molecular paleopathology: a novel perspective for biomedical history].
AB  - Molecular paleopathology is an emerging field that is devoted to the detection,
      indentification and characterization of the molecular signatures in past
      diseases. When studied with modern molecular techniques, ancient human remains
      may yield direct informations on the diseases of ancient populations as well as
      the history of human diseases. Data concerning specific diseases of infectious,
      neoplastic and genetic origin can be obtained by molecular investigations of
      skeletal and mummified human remains. In particular, ancient DNA extracted from
      bone tissue, teeth and mummified soft tissue can be deeply analyzed by using PCR
      based molecular techniques. Additionally, DNA of ancient pathogens, including
      bacteria, viruses and parasites, can be isolated from human remains and molecular
      diagnosis of infectious diseases can be made. Thus, molecular data, complemented
      by morphological and biochemical analyses, could help to reconstruct the
      epidemiology of past diseases and epidemics.

PMID- 16285091
TI  - [Maria Dalle Donne M.D. two century after her appointment as director of the
      School of Midwifery in Bologna].
AB  - In 1804, Maria Dalle Donne, graduated in Philosophy and Medicine, was appointed
      as director of the school for midwives in Bologna. This woman deserves without
      doubts to be remembered above all for her academical results that she achieved in
      a period in which it was absolutely exceptional for a girl of humble origin to be
      graduate but in particular because to her was attributed a prominent role in the
      formation of well trained women in important sector of public health. Although
      the documentation about her scientific production is scarce no one can miss her
      professional value and large estimation for the fact that her appointment was
      reconfirmed for nearly four decades in spite of institutional and political
      changes that took place in Bologna in that period.

PMID- 16285092
TI  - [The ambivalence of love: from physiologic need to disease of the soul and of the
      body].
AB  - In this writing we intend to examine the Epicurean notion of love as Lucretius
      presents it, both in the light of the perspective open by Jackie Pigeaud in an
      article on the erotic dream in antiquity and in a comparision with the Stoic
      view. We will notice the curious relationship there is between Lucretius' notion
      of simulacra and Stoic conception of phantasiai, but also the fundamental
      difference there is in their respective perception with what follows concerning
      the responsibility of the individual in his action. A passage of Seneca will show
      us that man can be morally corrupted to such an extent as to be able to shape up
      by himself negative phantasiai. But the portrait we will try to make of Epicurean
      and Stoic theory of love will give us the opportunity to see its integration into
      the medical thought of Roman imperial age. The attention of the most eminent
      physicians of I-II century to the pathological issues both for the soul and for
      the body of an excessive erotic life, indeed, not only depends on the heritage of
      Aristotelian acquisitions in the field of biology and psychology, but also
      presents some interesting links with Epicurean and Stoic theory of love,
      coherently with the pretension of some of these physicians to become the tutors
      of both physic and moral health of humanity.

PMID- 16285093
TI  - [Human science and medicine].
AB  - Objective of Human Science teaching is to develop Knowledge and ability for
      rational analysis of bio-medical problems. The relationship between doctor and
      patient must be founded on dialogue, cooperation, understanding, on respect of
      human rights: life, health, physical integrity, privacy, autonomy, freedom and
      liability to guide ethical choices in clinical experience and rediscover
      anthropological significance of Medicine.

PMID- 16285095
TI  - [What monitoring for the cirrhosis patient?].

PMID- 16285094
TI  - The embalming, the scientific method and the paleopathology: the case of Gaetano
      Arrighi (1836).
AB  - Since the most ancient times the problem of the artificial preservation of dead
      bodies has been an important object of study. In ancient and classic times the
      reasons leading to this practice were essentially of a religious and esoteric
      type, but in the modern age, following the development of medical and biological
      studies, embalming has assumed a more practical trend which is both medicine and
      scientific. The discovery of blood circulation has marked the scientific method
      which, in its various forms, has circulated all over Europe bringing fame to
      eminent anatomists such as Federico Ruysch (1638-1731), William (1718-1783) and
      John Hunter (1728-1793), Jean Nicolas Gannal (1791-1852), Giuseppe Tranchina,
      Laskowky and Brosch, who affirmed the embalming by endoarterial injection of
      conservation fluids making evisceration useless and obsolete. The advent of
      formalin and the introduction of new surgical and autoptic methods have made this
      practice gradually fall into disuse. For this reason, the mummy found in Leghorn
      (Tuscany, Central Italy) is of particular importance since was obtained applying
      the intravascular injection following the method, described by the Italian
      medical Giuseppe Tranchina in 1835. The mummified body belongs to Gaetano
      Arrighi, a prisoner in the Leghorn fortress. He was born in Arezzo in 1789 and
      died on March 1836 at the age of 47 in the Civil Hospital of Leghorn following
      pleurisy, as results in an annexed document. The day after his death Dr. Raimondo
      Barsanti from Pisa and Superintendent at the Leghorn hospital made up the
      Tranchina's method, which consisted in the injection of an arsencial -mercury
      solution inside of the blood vessels, giving rigidity and dark red color to the
      dead body. The excellent outcome of the intervention has made it possible, more
      than 160 years later, to study not only the method by which Arrighi's body was
      embalmed but also to perform a careful paleopathological imaging study by
      traditional X-rays and by Computer Axial Tomography (CAT). The high percentage of
      mercury present in the conservation fluid conferred radiopacity, making it
      possible to evidence the diffusion of the liquid into the entire artery tree and
      in particular into the aorta as well as in all the right and left artery systems.
      The radiopacity showed an unusual thoracic picture suggesting a pathological
      situation. The CAT study enriched and ameliorated the results obtained by X-rays
      making it possible to reconstruct the embalming procedure and to confirm the
      diagnosis of wet pleurisy probably cause by a tubercular infection.

PMID- 16285096
TI  - [Cirrhosis: candidates for liver transplantation].

PMID- 16285097
TI  - Community based participatory approaches to address health disparities in
      Hawai'i: recent applications in cancer prevention, detection and treatment
      programs.
AB  - Assessment of recent trends in the prevalence and incidence of cancer, and its
      associated risk and protective factors in the State of Hawai'i illustrate that
      there are definite ethnic, socio-economic, and geographic health disparities.
      Disparities in access to health care are reflected in decreased and under
      utilization of all types of preventive cancer screening tests and decreased
      proportions of people with health insurance coverage. Increases in obesity mirror
      U.S. national trends and disproportionately affect certain ethnic groups and
      those with low income. Tobacco use has increased among at-risk populations
      including: certain ethnic groups, those with low-income and/or low education and
      those in rural areas. Data that reveal continuing or worsening health disparities
      imply that either the old methods have not been effective and/or resources are
      not available or are not being applied to address such disparities. Promising
      methodologies and programmatic focuses to reduce health disparities are needed as
      mechanisms for improving the circumstances of at-risk populations. Community
      based participatory approaches are described here for cancer prevention,
      detection, and treatment programs that utilize culturally appropriate methods.

PMID- 16285098
TI  - [Differential diagnosis of an abdominal tumor].

PMID- 16285099
TI  - Adams v. State.

PMID- 16285100
TI  - Kevorkian v. Thompson.

PMID- 16285101
TI  - United States v. Jacobson.

PMID- 16285102
TI  - Kassama v. Magat.

PMID- 16285103
TI  - Kassama v. Magat.

PMID- 16285105
TI  - Itskov v. New York Fertility Institute.

PMID- 16285106
TI  - 66 Federal Credit Union v. Tucker.

PMID- 16285104
TI  - Kassama v. Magat.

PMID- 16285108
TI  - Kevorkian v. Arnett.

PMID- 16285107
TI  - Molloy v. Meier.

PMID- 16285110
TI  - J.B. v. M.B.

PMID- 16285109
TI  - J.B. v. M.B.

PMID- 16285111
TI  - [100 years since the discovery of auscultation measurement of arterial pressure].

PMID- 16285112
TI  - [Dr. Eduard Mihel (24 June 1864--24 March 1915)].

PMID- 16285114
TI  - Cord blood transplantation and cord blood banking.

PMID- 16285115
TI  - [The 45th annual meeting of the Japanese Society of Nuclear Medicine. Tokyo,
      Japan. November 11-13, 2005. Abstracts].

PMID- 16285116
TI  - [Guideline for the management of ALI/ARDS].

PMID- 16285117
TI  - [Guideline for the management of cough].

PMID- 16285118
TI  - Ethical genetic research on human subjects.
AB  - Since the Nuremberg trials and the Nazi doctors trial following World War II,
      international ethics protocols have emerged designed to protect human subjects
      from the atrocities of medical experimentation that were literally routine under
      the Nazis. Some of the apparent "lessons" from the Nazi period have been
      encapsulated in the Declaration of Helsinki, perhaps the leading medical ethics
      protocol. This paper argues that these protocols have not been notably conducive
      to human welfare or to the protection of human rights in the field of human
      genetics research. The paper proposes new protocols and a new approach to the
      ethics of research on human subjects.

PMID- 16285119
TI  - Necessary decisions.

PMID- 16285120
TI  - What wasn't discussed.

PMID- 16285121
TI  - Without a trace: how a lack of U.S. domestic LMO regulations is undermining
      international control.

PMID- 16285122
TI  - Whistleblowers, threats, and bribes: a short history of genetically engineered
      bovine growth hormone.

PMID- 16285124
TI  - Method may yield pluripotent stem cells without killing embryos: statement of
      thirty-five scientists and ethicists.

PMID- 16285123
TI  - You hypocrites!

PMID- 16285125
TI  - NIH sets up national stem-cell bank in Wisconsin.

PMID- 16285126
TI  - Abortion and the voice of scripture.

PMID- 16285127
TI  - Partial-birth abortion on trial.

PMID- 16285128
TI  - Rethinking the Patient Self Determination Act: implementation without
      effectiveness.

PMID- 16285129
TI  - Equity versus economics in South Korea.

PMID- 16285130
TI  - Bioethics and Christian theology.
AB  - The authors of this essay suggest that the field of bioethics and Christian
      theology have a great deal to offer each other. The authors first argue that
      representatives from both fields must first make sure that they fully and
      correctly represent their respective position. In other words, scientists,
      ethicists, and theologians alike must make sure that they present their fields
      and not use their knowledge merely for personal gain at the stake of misguiding
      people. Once this is established, the authors then proceed to show the intimate
      relationship between Christianity and medicine that has existed throughout the
      ages. It is a call for a continuation of such a relationship that the authors
      suggest between bioethics and theology. Through an integration of bioethics and
      Christian theology, both scientists/physicians and theologians are able to gain
      greater insight into the human person--a focus in both fields.

PMID- 16285131
TI  - Concordant spiritual orientations as a factor in physician-patient spiritual
      discussions: a qualitative study.
AB  - OBJECTIVES: To understand the impact of physicians' and patients'
      religious/spiritual orientation on discussions of spiritual issues. METHODS: We
      performed semi-structured interviews of 10 Missouri family physicians and 10
      patients of these physicians, selecting subjects nonrandomly to represent a range
      of demographic factors, practice types, and chronic or terminal illness. We coded
      and evaluated transcribed interviews for themes. RESULTS: Respondents expressed
      that similar belief systems facilitate patient-physician spiritual interactions
      and bring confidence to their relationships. Those holding dissimilar faiths
      noted limited ability to address spiritual questions directly. They cited
      significant barriers to spiritual interaction but considered that ecumenism, use
      of patient-centered care, and negotiation skills lessen these barriers.
      CONCLUSIONS: Our respondents view spirituality similarly to other aspects of the
      physician-patient relationship involving differing viewpoints. Where discordance
      exists, cross-cultural, patient-centered, diplomatic approaches facilitate
      spiritual discussions.

PMID- 16285133
TI  - Surgeons and the spirit: a study on the relationship of religiosity to clinical
      practice.
AB  - This study aimed to identify the religious practices and beliefs of surgeons and
      the relationship between surgeons' locus of control and religiosity. Thirty-five
      surgeons completed a survey that included items from the Duke University Religion
      Index, the Salesian Center Intrinsic Religiosity Scale for Clinicians, and
      Rotter's Locus of Control Scale. Over 68% of sampled surgeons affirmed that their
      religious beliefs play a part in their practice, 47% attend religious services at
      least weekly, and 44% pray daily. There was no correlation between locus of
      control and religiosity. These results challenge the myth of the egocentric,
      agnostic surgeon.

PMID- 16285132
TI  - A review of spiritual and religious measures in nursing research journals: 1995
      1999.
AB  - BACKGROUND: A series of systematic reviews has revealed relatively high levels of
      interest in religion and spirituality in different nursing specialties, but not
      in general nursing research journals. PURPOSE: To identify the extent to which
      spirituality and religiousness were measured in all quantitative and qualitative
      research articles published in Research in Nursing and Health, Nursing Research,
      Advances in Nursing Science (ANS), and Image: The Journal of Nursing Scholarship
      from 1995 to 1999. METHODS: A full-text search was conducted of ANS and Image
      using the Ovid search system. Nursing Research and Research in Nursing and Health
      were hand searched for spiritual/religious measures. Characteristics of selected
      studies, the measures taken, and their uses were coded for data analysis.
      RESULTS: A total of 564 research studies were identified, of which 67 (11.9%)
      included at least one measure of spirituality or religiousness. A significant
      difference was found between the percentage of qualitative and quantitative
      studies that contained measures of these concepts. Of the 119 qualitative
      studies, 23 (19.3%) contained a measure of religion or spirituality, compared to
      44 of the 445 (9.9%) quantitative studies. Nominal indicators of religious
      affiliation were the most commonly used measures in the quantitative studies and
      measures of religion and spirituality were rarely used in the analyses. Although
      only a few quantitative or qualitative studies intended to focus on religion or
      spirituality, these themes often emerged spontaneously in the qualitative
      research. CONCLUSIONS: Research in Nursing and Health, Advances in Nursing
      Science, Nursing Research, and Image: The Journal of Nursing Scholarship all
      published research measuring spirituality and religiousness during the time
      period studies. The rate at which spirituality and religion appeared in these
      nursing research articles is substantially higher than that found in most fields
      outside of nursing. Even more frequent inclusion of spiritual and religious
      variables and richer measures of spirituality and religiousness would help to
      increase the available scientific information on the role of spirituality and
      religion in nursing care.

PMID- 16285134
TI  - Ethical perspectives on life sciences research after mapping the human genome.
AB  - The essay discusses ethical perspectives of life sciences research that can help
      us navigate a path across the genetic landscape that opens before us with the map
      of the human genome that was announced recently. We can rightly anticipate many
      drug discoveries and genetic therapies to cure, prevent, or alleviate devastating
      conditions. But we must also pause with appropriate apprehension about the
      possible dangers and difficulties we may encounter.

PMID- 16285135
TI  - A rising cost of an education.

PMID- 16285136
TI  - Visualizing stress.

PMID- 16285138
TI  - Precise patterning in microfluidic devices.

PMID- 16285137
TI  - Measuring estrogen conjugates in sewage.

PMID- 16285139
TI  - Faster, cheaper DNA sequencing.

PMID- 16285140
TI  - Fishing for MAGIC targets.

PMID- 16285141
TI  - MS detectors.

PMID- 16285142
TI  - E. coli stick to the right.

PMID- 16285143
TI  - When microfluidic devices go bad. How does fouling occur in microfluidic devices,
      and what can be done about it?

PMID- 16285144
TI  - Rock varnish and the manganese oxide connection.

PMID- 16285147
TI  - Ethics committees and consensus in the post-totalitarian society.
AB  - Ethics committees are usually expected to reach and frame their decisions by
      consensus. In a post-totalitarian society the conception of consensus might
      somewhat differ from the one present in societies with a long-term, uninterrupted
      tradition of democratic development. In 1990s, post totalitarian societies of
      Central and East Europe have been walking difficult paths from the situation,
      when matters of public interest had been decided almost solely within the
      structures of a totalitarian power (usually a 'communist' party and by the party
      dominated governmental or municipal structures) and the political decisions
      implemented by more or less coercive exercise of that power (while requiring the
      broadest community attainment--'imposed consensus'); toward societies deciding
      their fate and matters of public interest via institutions of a modern,
      pluralistic, parliamentary democracy (subscribing implicitly or even explicitly
      to consensus, perceived mostly as 'overlapping' or 'procedural'). The paper gives
      an analysis of evolution of the notion of consensus in the post-totalitarian
      Slovakia as seen within the frame of the first decade of establishment and work
      of ethics committees in the institutions of biomedical research and health care.
      Examples of present challenges for ethics committees' consensual decision making
      are outlined.

PMID- 16285148
TI  - Recommendation 1512 (2001) [I]: protection of the human genome by the Council of
      Europe.

PMID- 16285149
TI  - Medicare program; changes to the hospital outpatient prospective payment system
      and calendar year 2006 payment rates. Final rule with comment period.
AB  - This final rule with comment period revises the Medicare hospital outpatient
      prospective payment system to implement applicable statutory requirements and
      changes arising from our continuing experience with this system and to implement
      certain related provisions of the Medicare Prescription Drug, Improvement, and
      Modernization Act (MMA) of 2003. In addition, the final rule with comment period
      describes changes to the amounts and factors used to determine the payment rates
      for Medicare hospital outpatient services paid under the prospective payment
      system. This final rule with comment period also changes the requirement for
      physician oversight of mid-level practitioners in critical access hospitals
      (CAHs). In this final rule with comment period, we also are responding to public
      comments received on the November 15, 2004, final rule with comment period
      pertaining to the ambulatory payment classification (APC) group assignment of
      Healthcare Common Procedure Coding System (HCPCS) codes identified in Addendum B
      of that rule with the new interim (NI) comment indicator. These changes are
      applicable to services furnished on or after January 1, 2006.

PMID- 16285150
TI  - Respect for the dignity of the dying person ethical observations on euthanasia.

PMID- 16285151
TI  - Address of John Paul II to the 18th International Congress of the Transplantation
      Society.

PMID- 16285152
TI  - Conjoined twins: the ambiguity of double effect reasoning.
AB  - This essay explores the ethical debate that surrounds last year's case of
      conjoined ischiopagus tetrapus twins, Mary and Jodie. More precisely, it focuses
      on those arguments that involved double effect reasoning (DER). A classic model
      of DER is offered, followed by a summary of the opinions of theologians and
      philosophers in debating whether such reasoning could be used to justify the
      surgical separation of these babies. The purpose is to show the "give and take"
      of ethical discourse, how complex and demanding the application of DER often is,
      and how elusive finding a "right answer" can be.

PMID- 16285153
TI  - The embryo: a sign of contradiction.

PMID- 16285154
TI  - Bioethics, sport and the genetically enhanced athlete.
AB  - This paper begins by acknowledging the interest taken by various international
      organisations in genetic enhancement and sport, including the US President's
      Council on Bioethics (July, 2002) and the World Anti-Doping Agency (March, 2002).
      It is noticed how sporting organisations have been particularly concerned to
      emphasize the 'threat' of genetics to sport, whereas other institutions have
      recognised the broader bioethical issues arising from this prospect, which do not
      readily reject the use of genetic technology in sport. Sports are identified as
      necessarily 'human' and 'moral' practices, the exploration of which can reveal
      greater insight into the intuitive fears about genetic modification. It is argued
      that anti-doping testing measures and sanctions unacceptably persecute the
      athlete. While there are substantial reasons to be concerned about the use of
      genetic modification in sport, the desire for policy ought not diminish the need
      for ethical research; nor ought such research embody the similar guise of
      traditional 'anti' doping strategies. Rather, the approach to genetics in sport
      must be informed more by broader social policies in bioethics and recognition of
      the greater goods arising from genetic technology.

PMID- 16285155
TI  - Borderline viability resuscitation cases.
AB  - Decisions on whether to resuscitate severely premature infants are especially
      difficult in "borderline viability" cases--those where the probability of
      survival is slim, and where, if survival is possible, multiple co-morbidities and
      severe disabilities are likely. The 2000 International Guidelines on
      Cardiopulmonary Resuscitation are comprehensive, yet leave open some of the more
      difficult ethical questions that must be addressed by decision-makers. This paper
      recommends evidence-based, clinical ethical guidelines for neonatal
      resuscitation, drawing on one large Catholic health system's approach, arguing
      from the perspective of the Catholic moral tradition and the Ethical and
      Religious Directives for Catholic Health Care Services (the ERD are policy for
      all of Catholic health care in the U.S.). The paper presumes that there is an
      inherent dignity of the human person to be respected and protected regardless of
      the nature of the person's health problem or social status. But it also presumes
      and argues that treatments can be justified only by a proportionate benefit to
      the patient. In maintaining a holistic view of the human person, two extremes are
      avoided: a "vitalistic" approach where life is preserved at all costs; and the
      "easy" alternative of euthanasia. Several principles of medicine, theology,
      ethics and Anglo-American common law are applied to three categories of preterm
      infants, each of which calls for a different basic response: Category I - infants
      with a confirmed gestational age of < 23-0/7 weeks; Category II - infants with a
      confirmed gestational age between 23-0/7 and 25-0/7 weeks; and Category III -
      infants with a gestational age > 25-0/7 weeks. Studies show that survival rates
      and outcomes vary dramatically for these three groups, even with the availability
      of the latest technologies.

PMID- 16285156
TI  - Trends in racial disparities in care.

PMID- 16285157
TI  - Trends in racial disparities in care.

PMID- 16285158
TI  - Trends in racial disparities in care.

PMID- 16285159
TI  - CD3-antibody therapy in new-onset type 1 diabetes mellitus.

PMID- 16285160
TI  - [Myringoplasty with a soft tissue plug in cases of residual perforations after
      tympanoplasty].

PMID- 16285161
TI  - The state of the electronic health record in 2005.

PMID- 16285162
TI  - Beyond electronic health records: quality outcomes management.

PMID- 16285163
TI  - Early adopters and lemmings: look before you leap into electronic records.

PMID- 16285164
TI  - Errors at the speed Light.

PMID- 16285165
TI  - Realizing it's potential.

PMID- 16285166
TI  - A shifting marketplace for physician services.

PMID- 16285167
TI  - Using mediation to resolve disputes in health care.

PMID- 16285168
TI  - How Taiwan does it: seeing more patients for less.

PMID- 16285169
TI  - Impact of formulary restrictions on patient safety.

PMID- 16285170
TI  - Leadership lessons learned from middle management.

PMID- 16285171
TI  - Management in residency training.

PMID- 16285172
TI  - A modest proposal: making referrals patient-friend.

PMID- 16285174
TI  - Using value innovation to create competitive advantage: part 2.

PMID- 16285173
TI  - Health of nations: government participation in medical care management.

PMID- 16285175
TI  - Clarifying your vision and objectives.

PMID- 16285176
TI  - [International League of Dermatological Societies (ILDS)--history, structure,
      mission and challenges].

PMID- 16285177
TI  - [Influenza vaccination and skin disease--coincidence or causal association?].
AB  - Influenza remains an important cause of morbidity and mortality worldwide;
      therefore, vaccination of risk groups is recommended by health authorities in
      many countries of the world. Vaccination against influenza has been implicated
      occasionally induce or trigger skin diseases. We review the literature and
      present data from the German registry for vaccination-associated adverse effects
      at the Paul-Ehrlich-Institut. In addition to local reactions at the injection
      site, exanthema, urticaria and anaphylactic reactions to vaccine components,
      vasculitis has been documented to be likely induced or triggered by influenza
      vaccination. Other skin diseases do not appear to be associated with vaccination
      to influenza. Overall, the risk of vaccination-associated skin disease is very
      low and is not a reason to avoid of influenza vaccination.

PMID- 16285178
TI  - [Pruritus--pathophysiology, clinical features and therapy--an overview].
AB  - Pruritus is an unpleasant sensory perception of the skin associated with the
      desire to scratch. As a physiological nociception, pruritus leads to the removal
      of harmful agents such as parasites and plants from the skin surface. More often,
      pruritus occurs as a severe and therapy-refractory symptom of various underlying
      dermatological and systemic diseases. Comparable to chronic pain, chronic
      pruritus worsens the general condition and may lead to physical and psychological
      exhaustion. Until the 1990s, pruritus had been regarded as an incomplete pain
      sensation. Only recently, itch was defined as a separate, pain-independent
      sensation with its own mediators, spinal neurons and cortical areas. These
      observations led to the development of new therapeutic modalities. This paper
      gives an overview of itch pathophysiology, clinical types and therapies.

PMID- 16285179
TI  - Intradermal injection of Newcastle disease virus-modified autologous melanoma
      cell lysate and interleukin-2 for adjuvant treatment of melanoma patients with
      resectable stage III disease.
AB  - BACKGROUND: The value of active specific immunotherapy (ASI) for the treatment of
      solid tumours still has to be assessed. The objective was to test an autologous
      tumour cell vaccine for adjuvant treatment of stage III melanoma patients.
      PATIENTS AND METHODS: After open vaccination of 12 patients, another 17 patients
      were recruited for a randomized double-blind trial comparing treatment with the
      vaccine (n = 9) and with a placebo (n = 8). Intracutaneous vaccinations were
      given postoperatively in weeks 2, 4, 6, 12, 24 and thereafter every 6 months if
      sufficient vaccine material was available. Patients were followed for 60-84
      months. RESULTS: Median disease-free survival time was 5 months for open-treated,
      4 months for verum-treated and 6 months for placebo-treated patients.
      Corresponding median overall survival times were 30.5, 18 and 18.5 months,
      respectively. There were no remarkable differences between the verum and the
      placebo group. CONCLUSIONS: Adjuvant treatment of melanoma patients with an
      autologous ASI vaccine did not show clinical efficacy in this cohort of melanoma
      patients.

PMID- 16285180
TI  - Pemphigoid gestationis: treatment with immunoapheresis.
AB  - BACKGROUND: Pemphigoid (herpes) gestationis is a rare blistering disease of
      pregnancy. Topical and systemic corticosteroids and antihistamines are usually
      sufficient for treatment. CASE REPORT: A patient suffering from severe, therapy
      resistant pemphigoid gestationis was successfully treated with the additional use
      of six sessions of immunoapheresis. Systemic corticosteroids could be tapered and
      serum autoantibody levels to bullous pemphigoid antigen 2 (BPAG2 = BP180)
      significantly dropped during this treatment. CONCLUSION: Immunoapheresis
      represents a helpful therapeutic option with few side effects for severe cases of
      pemphigoid gestationis, unresponsive to conventional treatment.

PMID- 16285181
TI  - [Multiple miliary osteomas of the face].
AB  - A 60-year-old man presented with multiple miliary osteomas of the face. This rare
      type of osteoma cutis is characterized by milia-like extra-skeletal bone
      formation in the cutis and/or subcutis of the face. Histologically, bony
      trabeculae with peripheral osteoblasts can be found next to lipocytes and
      haematopoietic cells. Primary osteoma seems to be derived from residual aberrant
      embryonic mesenchymal tissue. Surgical therapy is the most efficient treatment.
      We review clinical features, aetiology and therapy.

PMID- 16285182
TI  - [Cholesterol embolism after renal transplantation].
AB  - A 70-year-old woman developed localized livedo racemosa on the right buttock 2
      months after renal transplantation. The suspected diagnosis of cholesterol
      embolism was confirmed by histopathological demonstration of cholesterol crystals
      in the wall of a small artery. The gluteal region is supplied by blood vessels
      that branch off the internal iliac artery distal to the usual anastomosing site
      of the donor kidney. Cholesterol emboli dislocated in the course of a kidney
      transplantation can reach the gluteal region. Cholesterol embolism after renal
      transplantation as well as the observation of cholesterol crystals in the
      histological preparation are rare findings.

PMID- 16285183
TI  - [Interstitial granulomatous dermatitis without arthritis: successful therapy with
      hydroxychloroquine].
AB  - Interstitial granulomatous dermatitis is a rare entity characterized by cutaneous
      linear strands (the "rope sign") and rheumatoid arthritis. In the past years, 12
      other cases have been described with variable cutaneous symptoms. All showed
      similar histological features, resembling those of granuloma annulare or
      'palisaded neutrophilic and granulomatous dermatitis', suggesting a wide spectrum
      for a single entity. A 60-year-old patient presented with erythematous patches
      with an indurated, violaceous border resembling the "rope sign" on both flanks.
      The histological investigation revealed dense diffuse interstitial inflammatory
      infiltrates composed of eosinophils, neutrophils, lymphocytes, macrophages and
      multinucleated giant cells in the superficial and deep dermis. In the deep
      dermis, prominent eosinophilic degenerated collagen fibres with surrounding
      macrophages ('floating sign') occurred. In contrast to most previously described
      patients, our patient did not have arthralgias. The skin findings cleared
      following therapy with hydroxychloroquine.

PMID- 16285184
TI  - [Effects of ultraviolet radiation on the immune system].

PMID- 16285185
TI  - [Skin erosion of the heel].

PMID- 16285186
TI  - Why do we publish? Or, a challenge to the medical profession.

PMID- 16285187
TI  - [Herr Professor and Dr. of Medicine Urs Walter Schnyder on his 80th birthday].

PMID- 16285188
TI  - Importance of self-reported health-related quality of life in identifying the
      needs of elderly people with osteoarthritis.

PMID- 16285189
TI  - Health-related quality of life in older adults with symptomatic hip and knee
      osteoarthritis: a comparison with matched healthy controls.
AB  - BACKGROUND AND AIMS: Health-related quality of life (HRQOL) assessment is
      receiving increasing attention as an outcome measure in osteoarthritis (OA). The
      aims of this study were to compare HRQOL among older adults aged 55 to 78 years
      with hip and/or knee OA with those without OA, and to assess the influence of
      selected variables (sex, body mass index, radiographic OA severity, educational
      level, comorbidities) on HRQOL. METHODS: The generic Medical Outcome Study Short
      Form-36 item health status questionnaire (SF-36) was administered to a cohort of
      264 OA patients (105 with hip OA alone, 108 with knee OA alone, and 51 with both
      hip and knee OA) and 112 healthy controls. RESULTS: Compared with the healthy
      controls, OA of the lower extremities has a detrimental effect on the eight-scale
      profile score, as well as on physical and mental summary measures of the SF-36.
      The most striking impact was seen in the physical measures "physical
      functioning", "physical role" and "pain" (p<0.0001). No statistically significant
      differences in SF-36 scores were found among the three groups of OA patients. The
      physical and mental summary scales of the SF-36 were closely correlated
      (p<0.0001). One hundred and forty-five patients (54.9%) reported at least one
      chronic coexisting disease. There was a significant inverse association with
      measures of comorbidity (number of comorbidities and comorbidity index score) and
      both physical and mental summary scores of the SF-36 questionnaire. In patients
      with OA of the knee alone (but not in hip OA alone or hip and knee OA), the SF-36
      pain score was inversely correlated with years of formal education (p=0.016). In
      addition, the impact of hip and knee SF-36 dimensions was not influenced by the
      degree of radiographic severity. CONCLUSIONS: Older adults with OA of the lower
      extremities undergo a significant impact on multiple dimensions of HRQOL,
      compared with healthy controls. The use of a generic measure of HRQOL such as the
      SF-36, in studies of OA where comorbidity is common, should be useful in
      characterizing the global burden of this disease.

PMID- 16285190
TI  - Racial variations in self-reported osteoarthritis symptom severity among
      veterans.
AB  - BACKGROUND AND AIMS: This study aimed at examining factors related to
      osteoarthritis (OA) symptom severity in African American and Caucasian veterans
      (n=202). METHODS: OA symptom severity (lower extremity pain, stiffness, and
      physical function) was measured by the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC). We also examined whether racial differences existed
      when controlling for other important demographic and clinical variables,
      including age, gender, income, educational level, employment status, marital
      status, number of years with OA symptoms, location of arthritic joints (hip,
      knee, back, foot/ankle), use of exercise, and current use of OA medications.
      Lastly, we examined whether factors associated with self-reported OA symptom
      severity differed in African American and Caucasian veterans. RESULTS: The mean
      WOMAC score for African American veterans (on a scale of 0-96) was 54.6
      (SD=17.2), and the mean score for Caucasian veterans was 48.4 (SD=17.6; p=0.02).
      In a multivariable regression model including demographic and clinical variables,
      African American veterans had significantly higher WOMAC scores than Caucasians
      (3=0.185, p=0.009). In Caucasian veterans, greater number of years with OA,
      presence of hip OA, and a low income were associated with greater WOMAC scores.
      In African Americans, no use of exercise and the presence of OA in the hip or
      back were associated with greater WOMAC scores. CONCLUSIONS: Among this sample of
      veterans, African Americans had significantly higher WOMAC scores than Caucasians
      after controlling for other important demographic and clinical factors. Different
      and more intense treatment strategies may be needed for African American veterans
      with OA.

PMID- 16285191
TI  - Relationship between dual-task related gait changes and intrinsic risk factors
      for falls among transitional frail older adults.
AB  - BACKGROUND AND AIMS: Gait changes in dual-task conditions have been associated
      with an increased risk of falling in older adults, and become more important in
      increasingly frail older adults. We studied the relationship between commonly
      known intrinsic risk factors for falls and dual-task related gait changes among
      transitional frail older adults. METHODS: Walking time and number of steps were
      measured while walking alone and while walking with counting backward on a 10-m
      walkway in 66 transitional frail older adults (mean age 83.6+/-6.1, 84.9% women).
      Uni- and multiple linear regression analyses were performed to explore the
      relationship between dual-task related gait changes (walking time and number of
      steps) and age over 85 years, polymedication, psychoactive drugs, poor distance
      vision, abnormal mobility and cognitive impairment. RESULTS: Compared with
      walking alone, both walking time and number of steps increased significantly
      while counting backward (p<0.001). Polymedication and abnormal mobility were
      associated with a significant increase of walking time and number of steps
      (p<0.01 for unadjusted change, p<0.05 for adjusted change). CONCLUSIONS: Dual
      task related gait changes were closely correlated with polymedication and
      impaired mobility in our sample of transitional frail older adults. These
      findings give some insight into the complexity of performing attention-demanding
      tasks while walking and accentuate the need for multi-factorial, personalized
      intervention strategies, to prevent decline in dual-task performance in this fall
      prone population.

PMID- 16285192
TI  - Upper extremity fractures in the elderly: consequences on utilization of
      rehabilitation care.
AB  - BACKGROUND AND AIMS: While hip fractures represent the most dramatic consequence
      of osteoporosis, fractures of the humerus, forearm and wrist account for one
      third of the total incidence of fractures due to osteoporosis in the older
      population. The aim of this retrospective cohort study was to evaluate
      rehabilitation care utilization and associated factors in elderly individuals
      with upper limb fracture. METHODS: Over two years, 667 patients 65 years of age
      or older were studied, who presented to the emergency department either from
      their private homes or nursing homes with an upper extremity fracture. The
      following outcome variables were collected: gender; age; residence; location of
      fracture; treatment; discharge destination; length of hospitalization; length of
      stay in a rehabilitation facility; and ultimate place of habitation after the
      event. RESULTS: The most frequent sites of fracture were distal radius (37.2%)
      and proximal humerus (29.1%). Two-thirds of the patients were treated non
      operatively. Inpatient rehabilitation care was necessary for 248 patients (37.2%;
      length of stay, 46 days). Factors associated with increased care included older
      age (> or = 80 years), coming from private home, sustaining two fractures,
      fractures of the humerus, and operative treatment. Six percent of the patients
      required permanent nursing home care. CONCLUSIONS: Upper extremity fractures in
      older people often require prolonged hospitalization and therefore account for
      considerable health care costs. Reasons are more related to advanced age and
      living conditions than to particular injury or treatment.

PMID- 16285193
TI  - The impact of visual impairment on health, function and mortality.
AB  - BACKGROUND AND AIMS: Our aim was to determine the impact of visual impairment on
      self-rated health, function and mortality amongst a community-dwelling elderly
      cohort. METHODS: The study design was prospective and longitudinal, subjects
      being taken from an age-homogeneous, community-dwelling cohort comprising 452
      subjects aged 70 in 1990 and 839 subjects aged 77 in 1998. Comprehensive data
      were collected by structured interviews and medical examinations carried out
      during home visits. Data included each subject's demographic and socio-economic
      profile, medical history, physical findings, functional status and self-rated
      health status. Visual acuity was measured using a Snellen chart and visual
      impairment was defined as best-eye corrected visual acuity of 20/40 or worse on
      Snellen chart testing. RESULTS: Measured and self-reported visual impairment
      correlated closely, and were significantly more prevalent amongst subjects with
      low education and poor financial status. Visually impaired subjects showed
      significantly greater dependence in ADL and IADL, poor self-rated health, less
      ability to rely on friends, increased loneliness and, in men aged 77, increased
      visits to the emergency room and hospital admissions. Visual impairment at age 70
      significantly predicted poor self-rated health (p=0.029, OR 2.36, 95% CI 1.09
      5.10), dependence in ADL (p=0.007, OR 2.91, 95% CI 1.34-6.33), general tiredness
      (p=0.037, OR 2.40, 95% CI 1.06-5.44), and mortality, with a two-and-a-half-fold
      increase in risk of death at seven years (p=0.0017,OR 2.84, 95% CI 1.48-5.46).
      CONCLUSIONS: Visual impairment in the elderly increases the risk of social,
      functional and medical decline.

PMID- 16285194
TI  - Effects of aging on sensation of dyspnea and health-related quality of life in
      elderly asthmatics.
AB  - BACKGROUND AND AIMS: As the awareness of sensory stimuli is often impaired in
      older subjects, it has been hypothesized that the aging process may influence the
      perception of dyspnea. This study aimed at evaluating the aging-related
      difference in perception of spontaneously occurring dyspnea in adult asthmatics
      and at whether any such aging-related differences have an effect on the health
      related quality of life (HRQOL). METHODS: 18 elderly asthmatics (EA) aged >65
      years and 20 young asthmatics (YA) (age range 16-44 years) were recruited. In all
      subjects, 12-month asthma symptom score and respiratory function were recorded.
      Dyspnea was measured at rest by the Visual Analog Scale (VAS) and HRQOL by the
      St. George's Respiratory Questionnaire (SGRQ). RESULTS: Although the groups did
      not differ for FEV1% predicted, the EA showed lower VAS scores (9.9+/-19.8 mm vs
      19.5+/-17.0, p<0.05). As regards HRQOL, only the "Symptom" section of SGRQ showed
      lesser impairment in EA. CONCLUSIONS: Aging is associated with blunted sensation
      of dyspnea. This only partly attenuates the disease-related impairment in quality
      of life, and other factors are presumed to counterbalance this effect.

PMID- 16285195
TI  - Changes in instrumental activities of daily living disability after treatment of
      depressive symptoms in elderly women with chronic musculoskeletal pain: a double
      blind, placebo-controlled trial.
AB  - BACKGROUND AND AIMS: The purpose of this study was to assess the effect of
      antidepressant therapy on changes in instrumental activities of daily living
      disability in elderly female patients with musculoskeletal pain in a controlled
      study comparing active drugs with a placebo. METHODS: In an 8-week double-blind,
      placebo-controlled outpatient trial, 30 female patients (response rate 90.0%)
      between 70 and 79 were examined. They all had a history of clinically evident
      musculoskeletal pain, were afflicted with depressive symptoms, and could
      independently bathe, walk, dress, and transfer (e.g., from a chair) inside the
      house. The study was performed using the Center for Epidemiological Studies
      Depression Scale (CES-D), and Instrumental Activities of Daily Living (IADL).
      RESULTS: Compared with the placebo-group, significant changes in the CES-D
      (p<0.01) and IADL (p<0.01) scales were observed after eight weeks in the active
      drug-treated subjects. CONCLUSION: Treatment of depressive symptoms may be
      efficacious in reducing IADL disability in elderly female patients afflicted with
      musculoskeletal pain.

PMID- 16285196
TI  - Change in serum albumin and subsequent decline in functional status in older
      persons.
AB  - BACKGROUND AND AIMS: This study examines whether a three-year change in serum
      albumin concentration is associated with subsequent decline in functional status
      in older persons. METHODS: A total of 588 participants from the Longitudinal
      Aging Study Amsterdam aged 65-85 years were followed for six years. The three
      year change in serum albumin was classified in four groups: chronic low (< or =43
      g/L at both time points), decrease (decrease of 2.4% or more) from normal to low,
      decrease but still normal, and stable normal albumin (reference group). During
      the subsequent three years, absolute change and a decline of one standard
      deviation or more (termed substantial decline) in functional status was assessed.
      Functional status was measured in two ways: using performance tests and self
      reported functional ability. RESULTS: Substantial decline in functional
      performance and functional ability was observed in 243 persons (41.3%) and 133
      persons (22.6%), respectively. After adjustment for baseline functional status
      and potential confounders, chronic low albumin and a decrease from normal to low
      albumin were associated with a greater absolute decline in functional performance
      and in self-reported functional ability. Using the outcome substantial decline in
      functional status, only decrease to low serum albumin was associated with decline
      in functional ability [odds ratio (OR)=1.97; one-sided 95% Confidence Limit
      (CL)=1.09]. CONCLUSIONS: This study indicates that chronic low serum albumin is a
      determinant of decline in functional status. However, a decrease in serum albumin
      from normal to low levels but within the normal range was a stronger determinant
      of future decline in functional status. Change in serum albumin level within the
      normal range measured between two points in time may be used as a general marker
      of future functional decline.

PMID- 16285197
TI  - Long-term trends in major cardiovascular risk factors in cohorts of aging men in
      the European cohorts of the Seven Countries Study.
AB  - BACKGROUND AND AIMS: Time trends in major cardiovascular risk factors are
      described in cohorts of middle-aged men followed for 35 years in 9 European
      cohorts of Finland, The Netherlands, Italy, Serbia and Greece. METHODS: Men aged
      40 to 59 years at entry in the early 1960s were repeatedly re-examined 3 to 5
      times over the last 35 years. Systolic blood pressure, serum cholesterol, body
      weight and body mass index were considered for analysis, including study of aging
      (35 years of follow-up) and of generation effects (10 years for men aged 50-59 in
      the period 1960-1970 and separately 10 years for men aged 75-84 years in the
      period 1985-1995). RESULTS: For the aging effect, average systolic blood pressure
      increased approximately 15 mmHg over 25 years maintaining a steady state
      thereafter, the largest increases being found in Serbia and Greece. Average serum
      cholesterol varied between approximately 4.5 in Serbia and 6.5 mmo/L in Finland
      in about 1960. Twenty-five years later, the average level was about 6 mmol/L in
      all five countries and decreased slightly thereafter. Average body weight and
      body mass index increased in all countries for 25 years and levelled off
      thereafter. For the generation effect, average systolic blood pressure decreased
      in all countries, with the exception of men aged 50-59 in Serbia and men aged 75
      84 in The Netherlands. Average serum cholesterol uniformly increased in men aged
      50-59 for the younger age-class and slightly decreased in men aged 75-84. Average
      body weight and body mass index increased systematically in all countries and in
      both age groups. CONCLUSIONS: Major changes were the great increases in average
      systolic blood pressure and serum cholesterol level in Serbia and in systolic
      blood pressure level in Greece between 1960 and 1985, and the large decrease in
      average serum cholesterol in Finland between 1970 and 1995. Average body weight
      and body mass index showed universal increases in both middle-aged and older men
      after 1960.

PMID- 16285198
TI  - Reliability of heart rate variability in healthy older women at rest and during
      orthostatic testing.
AB  - BACKGROUND AND AIMS: In the older population, the reliability of heart rate
      variability (HRV) has only been evaluated in a few studies, in the supine
      position, and covering a broad sample of age and patients of both sexes. To
      document the relevance of using HRV analysis in healthy older women, the aim of
      this study was to evaluate the reliability of HRV indexes during three classical
      tests. METHODS: 33 healthy women (66.9+/-0.7 years old) performed two test
      sessions. Each session consisted of an ECG recorded in the supine position, first
      with free breathing (Test 1), then with controlled breathing (Test 2), and in the
      upright position (Test 3). Time and frequency HRV indexes were obtained by
      processing the ECG signals. Reliability was assessed between sessions using
      Student's paired t-test, intraclass correlation coefficient (ICC) and coefficient
      of variation (CV). RESULTS: There were no differences between the sessions. ICC
      showed good reliability for all HRV indexes. CV was low for absolute HRV indexes,
      except in Test 3 for parasympathetic indexes with modest CV. The CV of HRV ratio
      indexes were modest to high in all three tests. CONCLUSIONS: Time and absolute
      frequency HRV indexes are reliable when testing healthy older women. Our results
      support the use of such indexes in gerontology research, to assess the effects of
      clinical or pharmacological interventions on the autonomic nervous system.

PMID- 16285199
TI  - Differential risk factors for early and later hospital readmission of older
      patients.
AB  - BACKGROUND AND AIMS: This study aimed at analyzing rates and factors associated
      with early and later readmission (0-1 month and 2-3 months after discharge,
      respectively) of older people after index hospitalization. METHODS: This
      prospective observational study was conducted in two teaching hospitals. People
      70 years and over were interviewed within 48 h of emergency admission. Socio
      demographic and medical factors were collected, together with functional factors
      including Activities of Daily Living (basis and instrumental), cognitive state,
      and geriatric syndromes. Medical diagnosis, length of stay, and destination were
      collected at discharge, and patients were followed up by phone 1 and 3 months
      after discharge. During these interviews, outcomes on readmission,
      institutionalization, need for help, and death were evaluated. RESULTS: The
      population of 625 patients had a mean age of 80.0 years. The rate of early
      readmission (01 month) was 10. 7% and the overall rate within 3 months was 23.1%.
      Logistic regression analysis showed that variables predicting early readmission
      were previous hospitalization within 3 months, a longer length of stay, and a
      discharge diagnosis in chapter 8 (respiratory system) and chapter 10 (genito
      urinary system) of the ICD-9-CM. Variables predicting later readmission were
      previous hospitalization within 3 months, a discharge diagnosis in chapter 7
      (circulatory system) of the ICD-9-CM, and a poor pre-admission IADL score.
      CONCLUSIONS: In a medicalized population of older people, several risk factors
      may be identified for 0-1 month and 2-3 month readmission. Besides severe
      morbidities at discharge, diagnoses and previous hospitalization, pre-admission
      IADL was an independent risk factor for 2-3 month readmission.

PMID- 16285200
TI  - Brain volumes in healthy adults aged 40 years and over: a voxel-based morphometry
      study.
AB  - BACKGROUND AND AIMS: Gender and age effect on brain morphology have been
      extensively investigated. However, the great variety in methods applied to
      morphology partly explain the conflicting results of linear patterns of tissue
      changes and lateral asymmetry in men and women. The aim of the present study was
      to assess the effect of age, gender and laterality on the volumes of gray matter
      (GM) and white matter (WM) in a large group of healthy adults by means of voxel
      based morphometry. This technique, based on observer-independent algorithms,
      automatically segments the 3 types of tissue and computes the amount of tissue in
      each single voxel. METHODS: Subjects were 229 healthy subjects of 40 years of age
      or older, who underwent magnetic resonance (MR) for reasons other than cognitive
      impairment. MR images were reoriented following the AC-PC line and, after
      removing the voxels below the cerebellum, were processed by Statistical
      Parametric Mapping (SPM99). GM and WM volumes were normalized for intracranial
      volume. RESULTS: Women had more fractional GM and WM volumes than men. Age was
      negatively correlated with both fractional GM and WM, and a gender x age
      interaction effect was found for WM, men having greater WM loss with advancing
      age. Pairwise differences between left and right GM were negative (greater GM in
      right hemisphere) in men, and positive (greater GM in left hemisphere) in women (
      0.56+/-4.2 vs 0.99+/-4.8; p=0.019). CONCLUSIONS: These results support side
      specific accelerated WM loss in men, and may help our better understanding of
      changes in regional brain structures associated with pathological aging.

PMID- 16285201
TI  - Nosocomial bacteremia in very old patients: predictors of mortality.
AB  - BACKGROUND AND AIMS: Nosocomial Bacteremia (NB) is associated with high mortality
      in elderly patients. To determine specific prognostic factors for 7- and 30-day
      mortality in elderly patients with NB, we analysed the characteristics of 62 NB
      patients, retrospectively. METHODS: This retrospective study concerns 62 cases of
      NB diagnosed within a 3-year period in a geriatric department. Bacteremia is
      described according to CDC definitions. Epidemiological characteristics, co
      morbidities, clinical (activities of daily living (ADL) before NB) and biological
      findings (neutrophil count, lymphocyte count, albuminemia before NB) were
      collected for each patient. A systemic clinical reaction was defined by the
      presence of one of the following parameters: chills, hypothermia <36 degrees C or
      hyperthermia >38.5 degrees C, or shock. Types of micro-organism and source of NB
      were also collected. All variables were analysed for mortality at day 7 (7-day
      mortality) and at day 30 (30-day mortality). RESULTS: The 7-day mortality rate
      was 21% and the 30-day rate was 45%. In multivariate analysis, 7-day mortality
      was only associated with the absence of systemic clinical reaction [OR 9.7 (3.7
      25.7)]. Again, in multivariate analysis, 30-day mortality was associated with an
      ADL score <2 [OR 8.3 (4.3-16.4)] and cocci gram positive NB [OR= 3.6 (1.9-6.9)].
      CONCLUSIONS: The absence of any systemic clinical reaction as a single
      independent predictor for 7-day mortality suggests either a poorer immune
      response to nosocomial bacteremia or a delay in diagnosis. Functional status was
      the strongest predictor for 30-day mortality. In this population, further
      prospective studies need to include these factors to evaluate predictors of
      mortality for serious infectious diseases.

PMID- 16285202
TI  - No correlation between mini-nutritional assessment (short form) scale and
      clinical outcomes in 73 elderly patients admitted for hip fracture.
AB  - BACKGROUND AND AIMS: Malnutrition in general and protein deficiency in
      particular, both upon admission and during the recovery period, may adversely
      influence the clinical outcome after hip fracture. This study investigates the
      relationship between nutritional status measured by the Mini-Nutritional
      Assessment short form (MNA-SF) and biological markers in elderly hip-fractured
      patients. METHODS: A prospective study in a university hospital. The MNA-SF
      nutritional scale and laboratory values (serum albumin, cholesterol, total
      lymphocyte count) were assessed within three days after hip fracture surgery.
      RESULTS: Seventy-three patients were included: 61 (84%) were women and 12 men.
      Mean age was 81.5+/-7.1 years. Inhospital mortality was 10%. The mean MNA-SF
      score was 11+/-0.5 (range 3-14); according to these values, 39 patients (53%)
      were at risk of malnutrition. MNA-SF scores were not significantly correlated to
      patients' laboratory values. Fourteen episodes of nosocomial infection were
      diagnosed in 11 patients, and 6 patients developed pressure ulcers during
      hospitalization. CONCLUSIONS: MNA-SF test scale values reflect a clinical process
      in post-operative hip-fractured patients which is different from serum albumin,
      cholesterol or lymphocyte count.

PMID- 16285203
TI  - Ewing sarcoma in a geriatric patient.
AB  - Ewing Sarcoma has been the second most common primary osseous malignancy in
      childhood and adolescence. It has been described as a highly aggressive neoplasm.
      This is the oldest case report in the literature with Ewing Sarcoma.

PMID- 16285204
TI  - Expression of alpha5beta1 integrin and fibronectin during early pregnancy in
      pigs.
AB  - The implantation in pig is superficial and non-invasive, involving phases of
      apposition, adhesion and attachment of conceptuses to endometrial surface
      epithelium. The role of integrins and ECM proteins is suggested. In the study,
      the expression of beta5beta1 integrin and FN on conceptus trophectoderm and
      endometrium during implantation and early pregnancy was investigated. The
      immunohistochemical localization of alpha5beta1 integrin and FN was performed on
      formalin-fixed, paraffin-embedded tissue sections using the ABC method. The
      results indicate that both conceptus and uterus expressed alpha5beta1 integrin
      and FN during early porcine pregnancy. The most intensive staining for
      alpha5beta1 integrin and FN was found in conceptus trophectoderm and endometrial
      surface epithelium in all investigated periods. During placentation the
      immunohistochemical staining for both alpha5beta1 integrin and FN was increased
      in trophectoderm and all endometrial structures. Since placenta in pigs is non
      invasive, it can be suggested that both alpha5beta1 integrin and FN participate
      in molecular events leading to successful implantation and placentation in
      species with true epitheliochorial placenta.

PMID- 16285205
TI  - Establishment and characterization of primary and subsequent subcultures of
      normal mouse urothelial cells.
AB  - In this study, we report a reliable technique for the harvest, cultivation and
      expansion of monoculture of NMU. The NMU were harvested by two methods, directly
      from the urothelium in vivo and indirectly from the urothelial outgrowths of
      bladder explant cultures. Primary cultures and subsequent subcultures were
      propagated in the mixture of media MCDB 153 and Advanced-DMEM, and conditioned
      medium. Primary urothelial cells required an initial plating density of 1 x 10(5)
      viable cells/cm2 for survival, while passaged cells needed lower plating
      densities (1 x 10(4) viable cells per cm2). The cultured cells were identified as
      urothelial by their epithelioid morphology and by the positive immunofluorescence
      labelling of tight junctional proteins, occludin and ZO-1, adherens protein E
      cadherin and cytoskeletal protein cytokeratin 7. Markers of highly differentiated
      urothelial cells, cytokeratin 20 and uroplakins, were not expressed. Furthermore,
      the immunofluorescence labelling of occludin and cytokeratin 7 was not detected
      in later passages when urothelial cells replicated at a high rate. In spite of
      the use of conditioned medium derived from V79 fibroblast cell culture
      supernatant, the NMU in the primary cultures and subsequent subcultures expressed
      a basal/intermediate cell phenotype. In conclusion, we demonstrate that
      homogeneous long-term culture of NMU can be developed. Since powerful transgenic
      tools exist to manipulate the mouse genome, our findings should help design the
      mouse in vitro systems for studying the control mechanisms of urothelial cell
      proliferation, stratification and differentiation in health and disease.

PMID- 16285206
TI  - Genotoxicity of the Musi River (Hyderabad, India) investigated with the VITOTOX
      test.
AB  - The bacterial VITOTOX genotoxicity test was used to screen water samples
      collected from three different stations along the banks of the river Musi, in
      Hyderabad, India. Water was collected at three stations that differed from each
      other in the nature of the surrounding industrial and other activities. A number
      of different pollutants were also measured in water, soil and air samples. The
      three stations were found highly polluted and different with regard to the
      genotoxicity and toxicity of their samples. These results demonstrate the need
      for further biological studies in this area to generate valuable data on genomic
      instability, risk assessment of cancer, and to provide avenues for risk
      management.

PMID- 16285207
TI  - Changes of femoral bone tissue microstructure in transgenic rabbits.
AB  - Bone tissue microstructure of femur was investigated in transgenic New Zealand
      White rabbits with human factor VIII gene. Altogether 42 bones (24 from
      transgenic rabbits and 18 from non-transgenic ones) were analysed. Specimens were
      prepared using standard histological equipment, producing thin sections of
      approximately 80-100 microm. For histomorphometrical analysis areas, perimeters,
      minimum and maximum diameters of osteons' vascular canals and of osteons were
      measured. We found out that the basic structural pattern of femoral bone tissue
      was primary vascular longitudinal in both groups of rabbits. However, a new type
      of the bone tissue--fibrolamellar--was identified only in the transgenic rabbits.
      The measured variables of the osteons' vascular canals were higher in transgenic
      individuals in comparison with the nontransgenic ones (except for maximal
      diameter) and the differences were statistically significant (P < 0.05; P <
      0.01). We suppose that the observed differences could be associated with
      transgenesis. In an effort to explain these differences we compared the
      cytogenetic profile of bone marrow cells between transgenic and non-transgenic
      rabbits. A significantly higher rate of aneuploidy was observed in c-metaphase
      spreads of transgenic individuals as compared to non-transgenic ones (P < 0.001).
      Despite the fact that no hFVIII mRNA expression was found in the femur of
      transgenic rabbits, we discussed an association of transgene integration into the
      genome and microstructural changes in the bone. In any case, the results indicate
      that transgenesis can also produce changes in other tissues than in the target
      ones.

PMID- 16285208
TI  - Presence of Chlamydia pneumoniae DNA in the artery wall--biomarker of coronary
      artery disease.
AB  - Many authors have shown an association between Chlamydia pneumoniae (CPn)
      infection and coronary artery disease (CAD). However, whether CPn infection
      demonstrated by CPn DNA presence in the artery wall plays an important role in
      pathogenesis of CAD and acute coronary events (i.e. unstable angina) remains to
      be elucidated. One hundred and fifteen consecutive patients with CAD (51 with
      unstable angina and 64 with stable angina) were compared with 52 control subjects
      with aortic valve disease without angiographic evidence of CAD. The presence of
      CPn DNA in the aortic wall was assessed with nested polymerase chain reaction
      (PCR), and the IgM, IgG and IgA anti-CPn titres were assessed with
      microimmunofluorescence test. CPn DNA presence in the artery (i.e. aortic) wall
      was associated with 3.7-fold increased risk of CAD (95% CI 1.2-11.3, P < 0.01);
      however, no statistically significant difference in CPn DNA presence was
      demonstrated between unstable and stable angina (17.6% vs. 25%). In the CPn DNA
      positive group more often than in the CPn DNA negative group, serological signs
      of chronic infection (55.2% vs. 27%, P = 0.004) were demonstrated, whereas no
      statistically significant differences were demonstrated in prevalence of either
      acute infection (9.3% vs. 0%) or reinfection (0% vs. 0%). In conclusion, CPn DNA
      presence in the artery (i.e. aortic) wall was associated with CAD, therefore may
      be used as a biomarker for CAD. Moreover, no statistically significant
      differences in CPn DNA presence in the artery wall and in serology were present
      between unstable and stable angina; therefore, CPn infection does not seem
      implicated in triggering an acute coronary event.

PMID- 16285209
TI  - Toll-like receptors. I. Structure, function and their ligands.
AB  - The innate immune system senses invading microorganisms by a phylogenetically
      conserved family of proteins PRRs of which TLRs are ones of the most important.
      There are at least 10 different TLRs in humans and 11 in mice. They have in the
      course of evolution specialized for the recognition of conserved structures among
      microorganisms called PAMPs. Activation of TLRs results in induction of innate
      immunity mechanisms as well in development of antigen-specific adaptive immune
      responses, thus bridging innate and adaptive immunity.

PMID- 16285210
TI  - The use of ethnic minority populations in published psychological research, 1990
      1999.
AB  - For this study, the authors analyzed the contents of 16 psychology journals for
      the presence of empirical articles on African Americans, Latinos, Asians, and
      Native Americans during the period ranging from 1990 to 1999. In 6 APA journals,
      there was a low percentage (4.7%) of such articles. African Americans were the
      most studied ethnic group. Data collected for this study also indicated that
      minority research has been increasing more in non-APA journals than in APA
      journals. In both APA and non-APA journals, counseling-oriented journals had
      higher percentages of minority articles than did journals of other
      subdisciplines. Possible explanations, consequences, and suggestions for future
      research are discussed.

PMID- 16285211
TI  - The influence of national culture on the perceived fairness of grading
      procedures: a comparison of the United States and China.
AB  - Although the desire to be treated fairly is a fundamental human preference,
      perceptions of fair treatment can be influenced by cultural beliefs and values.
      For this article, the author used a scenario-based experimental study to examine
      students' fairness perceptions of grading procedures in 2 countries with distinct
      national cultures, China and the United States. The results suggest that culture
      can influence students' perceptions of the fairness of 2 aspects of procedural
      justice: voice and interpersonal justice. Chinese students were more likely to
      value interpersonal justice (i.e., being treated with dignity and respect, and
      being provided with explanations of grading procedures) and perceived the lack of
      interpersonal justice as less fair than did U.S. participants. In contrast, U.S.
      students were more likely to perceive voice (i.e., the opportunity to discuss and
      appeal a grading decision) as fair. These findings are connected to differences
      in the cultural values of the United States and China.

PMID- 16285212
TI  - Language and modeling word problems in mathematics among bilinguals.
AB  - The study was conducted to determine whether the language of math word problems
      would affect how Filipino-English bilingual problem solvers would model the
      structure of these word problems. Modeling the problem structure was studied
      using the problem-completion paradigm, which involves presenting problems without
      the question. The paradigm assumes that problem solvers can infer the appropriate
      question of a word problem if they correctly grasp its problem structure.
      Arithmetic word problems in Filipino and English were given to bilingual
      students, some of whom had Filipino as a first language and others who had
      English as a first language. The problem-completion data and solution data showed
      similar results. The language of the problem had no effect on problem-structure
      modeling. The results were discussed in relation to a more circumscribed view
      about the role of language in word problem solving among bilinguals. In
      particular, the results of the present study showed that linguistic factors do
      not affect the more mathematically abstract components of word problem solving,
      although they may affect the other components such as those related to reading
      comprehension and understanding.

PMID- 16285213
TI  - Self-structure and postpartum dejection in first-time mothers.
AB  - Twenty-nine first-time mothers completed the Beck Depression Inventory (A. T.
      Beck, C. H. Ward, M. Mendelson, J. Mock, & J. Erbaugh, 1961) at Time 1 (3rd
      trimester) and at Time 2 (3-6 months after delivery). At Time 1, women described
      each of 20 self-aspects by repeatedly selecting from a list of 36 traits; they
      also reported the size of their social support network in a structured interview.
      At Time 2, the new mothers completed a short measure of mother role stress and
      described postpartum difficulties to an interviewer. The authors used
      HIerarchical CLASses (HICLAS; P. De Boeck & S. Rosenberg, 1988) to
      idiographically model each woman's self-descriptive data and to identify the
      class that contained each woman's most superordinate (cardinal) traits, which
      were then coded either as agentic or social-emotional. Postpartum difficulty
      predicted Time 2 dejection, but mother role stress and social network size did
      not. However, the content of the most superordinate trait class moderated the
      latter two effects. New mothers coded as agentic were more dejected than were new
      mothers coded as social-emotional when there was high mother role stress and when
      there was a large social support network.

PMID- 16285214
TI  - The general self-efficacy scale: multicultural validation studies.
AB  - General self-efficacy is the belief in one's competence to cope with a broad
      range of stressful or challenging demands, whereas specific self-efficacy is
      constrained to a particular task at hand. Relations between general self-efficacy
      and social cognitive variables (intention, implementation intentions, outcome
      expectancies, and self-regulation), behavior-specific self-efficacy, health
      behaviors, well-being, and coping strategies were examined among 1,933
      respondents in 3 countries: Germany (n = 633), Poland (n = 359), and South Korea
      (n = 941). Participants were between 16 and 86 years old, and some were dealing
      with stressful situations such as recovery from myocardial events or tumor
      surgery. Perceived self-efficacy was measured by means of the General Self
      Efficacy Scale (R. Schwarzer & M. Jerusalem, 1995). Meta-analysis was used to
      determine population effect sizes for four sets of variables. Across countries
      and samples, there is consistent evidence for associations between perceived self
      efficacy and the variables under study confirming the validity of the
      psychometric scale. General self-efficacy appears to be a universal construct
      that yields meaningful relations with other psychological constructs.

PMID- 16285215
TI  - Body image, relationships, and time.
AB  - The cultural standard of an impossible-to-attain ideal body image has been blamed
      for a plethora of psychological ills, from low self-esteem to eating disorders.
      In this study, the authors investigated the importance of current body image
      dissatisfaction compared with the ideal for married couples and for single
      people. The results indicated that although body image dissatisfaction exists in
      both married and single people, this discrepancy is of significantly less
      importance to married couples. The importance of long-lasting, satisfying
      relationships decreases the importance of body dissatisfaction and mitigates the
      impact of unrealistic ideal body image.

PMID- 16285216
TI  - The causes of loneliness in homeless youth.
AB  - Both homelessness and loneliness are pervasive in North America. In this study,
      the author compared the causes of the loneliness experienced by young homeless
      youth (n = 113) with that of counterparts in the general population (n = 211) who
      answered a 30-item yes-no questionnaire. The results identified 5 causes of
      loneliness: personal inadequacy, developmental deficits, unfulfilling intimate
      relationships, relocation or significant separations, and social marginality. The
      results indicated that the causes of loneliness in young homeless youth are
      significantly different from those of the general population.

PMID- 16285217
TI  - Plan and operation of Cycle 6 of the National Survey of Family Growth.
AB  - OBJECTIVES: This report describes how Cycle 6 of the National Survey of Family
      Growth (NSFG) was designed, planned, and implemented. The NSFG is a national
      survey of women and men 15-44 years of age designed to provide national estimates
      of factors affecting pregnancy and birth rates; men's and women's health; and
      parenting. Cycle 6, conducted in 2002, was the first time the NSFG included a
      sample of males. METHODS: The survey used in-person, face-to-face interviews
      conducted by trained female interviewers. One person per household was
      interviewed from a national area probability sample in about 120 sample areas,
      with oversamples of teenagers, African Americans, and Hispanics. The data
      collection used computer-assisted personal interviewing (CAPI). Separate
      questionnaires were used for female and male respondents. The last section of the
      questionnaires used a technique called audio computer-assisted self-interviewing
      (ACASI). In order to control costs and nonresponse errors, survey managers
      statistically analyzed results from interviewers' visits to sampled households
      each day, and used those results to allocate interviewer labor and other
      resources more efficiently. This management improved response rates and made the
      sample more representative. RESULTS: Over 12,500 interviews were completed, about
      7,600 with females and about 4,900 with males. The response rate was about 80
      percent for females and about 78 percent for males. The survey procedures were
      adapted during the fieldwork to achieve the desired response rates and to control
      costs.

PMID- 16285218
TI  - Disaster preparedness: lessons learned from the response to Hurricane Katrina.

PMID- 16285219
TI  - JCAHO to look closely at patient handoffs.

PMID- 16285220
TI  - 2005 salary survey results. Quality's power, importance increasing, but so is
      workload.

PMID- 16285221
TI  - Surveyors quiz staff with their own prep tools.

PMID- 16285222
TI  - Move from information transfer to exchange.

PMID- 16285223
TI  - Treatment options and considerations for the newly diagnosed myeloma patient.

PMID- 16285224
TI  - Modern management of recurrent ovarian carcinoma. A systematic approach to a
      chronic disease.
AB  - The management of ovarian cancer entails a complex blend of medical and surgical
      interventions. Managing patients with recurrent ovarian cancer increases the
      complexity of therapies and adds palliative interventions. The presence of
      recurrent ovarian cancer is both emotionally and physically taxing for patients
      as well as their caregivers. With an increasingly informed patient population, a
      balance must be achieved between easily accessible information enabling patients
      to know that they now have an incurable disease and support for their hopes and
      desires to still overcome their cancer. The decision tree in the management of
      recurrent ovarian cancer blends many different factors. This discussion will
      separate those factors as if they are pure elements. We will address management
      based on response to primary therapy and time to recurrence, the location of
      recurrence, symptoms of recurrence, the patient's histopathology, and the
      patient's primary stage as it relates to the extent of disease present at the
      start of chemotherapy.

PMID- 16285225
TI  - Update on malignant mesothelioma.
AB  - Mesotheliomas are uncommon in the United States, with an incidence of about 3,000
      new cases per year (or a risk of about 11 per million Americans per year).
      Incidence and mortality, however, are probably underestimated. Most are
      associated with asbestos, although some have arisen in ports of prior radiation,
      and a reported association with simian virus (SV)40 remains controversial. About
      85% of mesotheliomas arise in the pleura, about 91% in the peritoneum, and a
      small percentage in the pericardium or tunica vaginalis testis. The histology of
      about half of mesotheliomas is epithelial (tubular papillary), with the remainder
      sarcomatous or mixed. Multicystic mesotheliomas and well-differentiated papillary
      mesotheliomas are associated with long survival in the absence of treatment and
      should be excluded from clinical trials intended for the usual rapidly lethal
      histologic variants of the disease. The median survival is under a year, although
      longer median survivals for selected patients, particularly those with epithelial
      histology, have been reported in some combined-modality studies. Recent
      randomized trials have shown significant improvement in time to progression and
      survival for the addition of new antifolates to platinum-based chemotherapy.

PMID- 16285226
TI  - Clinical trials referral resource. Current clinical trials in rhabdomyosarcoma.

PMID- 16285227
TI  - Management of patients with muscle-invasive and metastatic bladder cancer.
AB  - Bladder cancer is the fifth most common cancer diagnosed in the United States.
      Prognosis for this disease is dependent on both tumor stage and grade. Radical
      cystectomy has been the standard treatment for muscle-invasive local disease;
      however, combined-modality approaches with the use of chemotherapy are gaining
      momentum with data suggesting survival improvement. Patients with metastatic
      disease have poor long-term survival rates despite systemic multiagent
      chemotherapy. A variety of agents, including newer cytotoxic drugs and
      biologically targeted agents, are under investigation to determine the most
      effective regimen. The special needs of specific patient populations, such as the
      elderly, those with a suboptimal performance status, and patients with medical
      comorbidities have gained more attention. Progress in the treatment of this
      disease is dependent on supporting ongoing and future clinical trials.

PMID- 16285228
TI  - Improving palliative and supportive care in cancer patients.
AB  - Twenty years of research in controlling symptoms such as pain and nausea have
      shown persistent suboptimal performance by the US oncology system. The data
      suggest that some of the tools of palliative care programs can improve physical
      symptoms of seriously ill patients at a cost society can afford. To fix these
      problems will require recognition of the symptoms or concerns, a system such as
      an algorithm or care plan for addressing each, measurement of the change, and
      accountability for the change. Symptom assessment scales such as the Edmonton
      Symptom Assessment Scale or Rotterdam Symptom Check List work to make symptoms
      manifest. Listing symptoms on a problem list is a necessary step in addressing
      them. Physical symptoms such as pain can be improved by use of computer prompts,
      algorithms, dedicated staff time, team management, or combinations of these
      strategies. Less concrete problems such as medically appropriate goal-setting,
      integrating palliative care into anticancer care sooner, and informing patients
      about the benefits and risks of chemotherapy near the end of life require more
      complex solutions. We review what is known about symptom control in oncology, how
      and why some programs do better, and make suggestions for practice. Finally, we
      suggest a practical plan for using symptom assessment scales, listing the
      problems, and managing them according to algorithms or other predetermined plans.

PMID- 16285229
TI  - IgE-reactive carbohydrate epitopes--classification, cross-reactivity, and
      clinical impact (2nd part).

PMID- 16285230
TI  - Time course of total and food specific IgE antibodies (Rast Fx5) in the
      developing allergic child.
AB  - AIM: To analyze the evolution of total and food specific IgE (Rast Fx5) titers in
      the course of food allergy in children. PATIENTS & METHODS: 925 children, mean
      age 8.9 + 9.1 years (15 days-18 years), 455 girls and 470 boys, investigated for
      food allergy in year 1997, underwent serum samples assay for total IgE and of
      Rast Fx5, Cap System, Pharmacia & Upjohn Diagnostics AB, Uppsala, Sweden, a mix
      test detecting specific IgE to 6 major food allergens in children, cow's milk
      proteins (CMP), egg white, peanut, soy, wheat and fish and analyzed as a function
      of reference values by age. RESULTS: Total IgE titers increased significantly
      with age, r0.22, p0.0001. The percentage of children with a total IgE level above
      normal range first increased with age, from 10.3 % at 0-6 months, reaching 38.2 %
      at 1-2 years and peaking at 56.9% at 4-6 years, then leveled off, 48.1% at 8-12
      years (ns vs 4-6 years) and 41.3% above 12 years (ns). Detectable Rast Fx5
      increased in a parallel manner until age 4-6 years and then exhibited a
      progressive decrease from age 6-8 years, differing significantly from total IgE:
      31.9% vs 52.9%, p0.01 (6-8 years), 32.2% vs 48.1%, p0.03 (8-12 years), 21.8% vs
      41.3%, p0.05 (> 12 years). CONCLUSION: In these outpatient children investigated
      for food allergy, the increase with age of the percentage of high total IgE
      contrasted with the progressive decrease of Rast Fx5 from age 4-6 yr. This
      biological finding correlates timely with the clinical spontaneous decrease of
      food allergy in the developing child.

PMID- 16285231
TI  - Where do we stand: the basic treatment of asthma and atopy: are we making
      backward progresses?

PMID- 16285232
TI  - Looking for immunotolerance: a case of allergy to baker's yeast (Saccharomyces
      cerevisiae).
AB  - We describe one case of baker's yeast true allergy in a boy with previously
      diagnosed mite-allergy and atopic dermatitis. At the age of 6, being atopic
      dermatitis and rhinitis well controlled by drugs, he began to experience
      generalized urticaria and asthma after eating pizza and bread, but only fresh
      from the oven. The diagnostic workup revealed single sensitization to baker's
      yeast (Saccharomyces cerevisiae), and a severe systemic reaction also occurred
      during the prick-by-prick procedure. After discussing with parents, no special
      dietary restriction was suggested but the use of autoinjectable adrenaline and on
      demand salbutamol. A diary of symptoms was recorded by means of a visual-analog
      scale. During the subsequent 2 years, the severity of symptoms was progressively
      reduced, and presently urticaria has disappeared. Only cough persists,
      invariantly after eating just-baked and yeast-containing foods. If bread, pizza
      and cakes are ate more than one hour after preparation, no symptom occur at all.
      Baker's yeast is a common component of everyday diet and it usually acts as an
      allergen only by the inhalatory route. We speculate that the continuous exposure
      to saccharomyces in foods may have lead to an immunotolerance with a progressive
      reduction of symptoms, whereas why the allergens is active only in ready-baked
      foods remains unexplained.

PMID- 16285233
TI  - Immunoblot studies in allergic patients to hymenoptera venom before and during
      immunotherapy.
AB  - BACKGROUND: Hymenoptera venom immunotherapy (VIT) is immunologically effective in
      patients with systemic allergic reactions after hymenoptera stings. OBJECTIVE: To
      evaluate the effect of VIT on specific IgE and IgG4 immunoblotting bands in VIT
      treated patients. MATERIAL AND METHODS: Specific IgE and IgG4 immunoblotting
      bands for hymenoptera venom were performed with ALABLOT in sera of 17 patients (8
      allergic to honeybee venom, 8 to wasp and 1 to polistes venom) before and during
      successful VIT (1 and 3 years). Before immunotherapy, all patients had
      experienced moderate/severe systemic reactions to a hymenoptera sting, with
      positive skin tests and venom-specific IgE. During immunotherapy all patients
      suffered field stings, without any systemic reaction. RESULTS: Before VIT we
      detected several immunoglobulin-binding bands in different regions, with
      different individual patterns. After VIT, we observed in some patients (5/8 for
      honeybee venom, 6/8 for wasp and 1/1 for polistes) complete disappearance of some
      IgE-binding bands, mainly the 15 kDa region (honeybee) and 23 and 44 kDa regions
      (wasp and polistes). All patients showed decreased intensity of IgE-binding
      bands, most pronounced in regions 16, 44 and 52 kDa (honeybee); 44 and 35 kDa
      bands (wasp) and 23 kDa (polistes). Some patients showed de novo appearance of
      IgG4-binding bands (4/8 for honeybee and 8/8 for wasp venom), mainly in 52 kDa
      (honeybee) and in 23 and 44 kDa regions (wasp). All patients showed increased
      intensity of IgG4 bands that were already present before VIT, more pronounced in
      52 and 44 kDa (honeybee) and in 44 and 35 kDa regions (wasp). CONCLUSIONS: During
      successful VIT there are changes in intensity and number of IgE and IgG4 binding
      bands, which could reflect the immunological improvement induced by VIT. These
      changes are more pronounced/frequent in wasp VIT, a fact that could explain the
      best results usually seen in these patients.

PMID- 16285234
TI  - Aspirin and non steroidal anti-inflammatory drugs hypersensitivity review (2002
      2004).
AB  - According to physician, Aspirin and NSAIDS hypersensitivity are causing three
      major problems: how to make the diagnosis? Which treatment are to he given to
      these patients? What kind of anti-inflammatory drugs are to be prescribed? For
      these last three years, several articles regarding these matters were being
      published.

PMID- 16285235
TI  - Maize flour-induced rhinitis.
AB  - Food allergy rarely causes allergic rhinitis. We report the case of a patient who
      developed non-occupational persistent rhinitis in adult age, evoked by the
      ingestion of maize (corn) flour. The symptoms and typical reactions of food
      allergy occurred only 15 years after the onset of the rhinitis signs.

PMID- 16285236
TI  - [A method for determination of the effective dose received by patient during
      digital scanning fluorographic examination from the results of measurement of
      radiation dose scattered by patient's body].
AB  - An original method for determination of the effective dose received by patient
      during digital scanning fluorographic examination from the results of measurement
      of radiation dose scattered by patient's body was suggested. This method does not
      require radiation detector to be exposed to working field. This method of
      determination of the effective dose of radiation scattered by patient's body can
      be used in scanning radiography.

PMID- 16285237
TI  - [Specific features of the use of microfocal radiography in medical diagnosis].
AB  - Specific features of imaging with microfocal X-ray technologies in medical
      diagnosis are described. In particular, the principal cause of the decrease in
      the radiation doses received by patients with different bone structure is
      discussed.

PMID- 16285238
TI  - [Determination of the dynamic range of digital X-ray receivers].
AB  - Specific features of determination of the dynamic range of digital X-ray
      receivers are considered. Various procedures for dynamic range determination are
      compared. The minimal permissible and optimal dynamic ranges are estimated.

PMID- 16285239
TI  - [Determination of the detective efficiency of X-ray diagnostic systems by visual
      assessment of the maximal resolution].
AB  - Methods of calculation of the detective efficiency of X-ray diagnostic systems
      and corresponding radiation dose are discussed. These methods are based on
      evaluation of limiting visually detectable resolution of a test pattern.
      Resulting dose values are compared with those inherent in an ideal system.

PMID- 16285240
TI  - [Specific features of high-voltage microfocal medical X-ray diagnosis].
AB  - A qualitative explanation and quantitative estimation of the decrease in the
      radiation dose received by patient during microfocal X-ray diagnostic examination
      are presented. The change in the image contrast with increasing X-ray tube
      voltage is described.

PMID- 16285241
TI  - [A family of radiation kilovoltmeters].
AB  - Three variants of specifications of control devices designed to monitor
      electrical and radiation characteristics of X-ray apparatuses are described.
      These are: autonomous device, device with portable (pocket), computer, and device
      compatible with automated working place of roentgenologist. Results of
      experimental tests are discussed.

PMID- 16285242
TI  - [On systematization of engineering tests of X-ray diagnostic equipment under
      conditions of treatment-and-prophylaxis institutions].
AB  - Protocols of engineering tests of X-ray diagnostic equipment are considered.
      Results of testing of an X-ray diagnostic device and corresponding testing
      software are described.

PMID- 16285243
TI  - [To the 60th anniversary of foundation of the Laboratory of X-ray Receivers,
      Russian Scientific Center for Roentgenoradiology. Part I: From birth to
      recognition].
AB  - The evolution of X-ray phosphors, screens, and films from the 1940s to present
      day and the contribution of the Laboratory of X-Ray Receivers, Russian Scientific
      Center for Roentgenoradiology, to this process are considered. It is shown that
      this evolution was mainly due to the attempts to obtain maximal diagnostic
      information with minimal dose load on patients and medical personnel. As a
      result, a family of intensifying screens was developed on the basis of
      traditional calcium-tungstate and zinc-cadmium-sulfide phosphors, as well as new
      phosphors based on rare-earth oxysulfides, oxyhalides, and tantalites and barium
      fluorohalides. The classification, properties and fields of application of the
      screens of all types are described. The permissible limits of the main X-ray film
      characteristics and the parameters of their processing are discussed from the
      same point of view. The research into this area will be apparently combined with
      further development of digital radiography and its introduction into medical
      practice.

PMID- 16285244
TI  - [Targeting and adjustment systems].
AB  - Various targeting and positioning systems based on ultrasonic and X-ray
      techniques are discussed. Specifications of four models of lithotrites are
      described. The advantages of online positioning are demonstrated.

PMID- 16285245
TI  - [Analysis of equipment of the Russian X-ray Mammological Service in 2003-2004].
AB  - Equipment of the Russian X-Ray Mammological Service in 2003-2004 is analyzed.

PMID- 16285246
TI  - [Analysis of the advantages of digital X-ray apparatuses over film X-ray
      apparatuses].
AB  - A comparative review of characteristics of film and digital detectors of X-ray
      apparatuses. Advantages of digital X-ray apparatuses over film X-ray apparatuses
      are discussed.

PMID- 16285247
TI  - [Experience in the use of a test phantom for checking the biopsy needle position
      in stereotactic mammography].
AB  - The possibility of the use of a special test phantom for checking the biopsy
      needle positioning accuracy in mammographic stereotactic devices is discussed.
      The test phantom meets the requirements of the state standard GOST R50267.45.

PMID- 16285248
TI  - [A cermet X-ray tube for mammography].
AB  - Characteristics of a new cermet X-ray tube for mammography are considered. The
      results of experimental testing of the tube are described.

PMID- 16285249
TI  - [Comparison of digital fluorographs ProScan-2000 and ProMatrix-4000].
AB  - Comparative analysis of characteristics of digital fluorographs of two types:
      scanning fluorographs and fluorographs with optical camera (screen-optics-CCD).
      It was shown that losses in the optical system of fluorographs of the second type
      caused significant deterioration of image quality.

PMID- 16285250
TI  - Stem cell plasticity and tissue replacement.

PMID- 16285251
TI  - The use of pancreas biopsy scoring provides reliable porcine islet yields while
      encapsulation permits the determination of microbiological safety.
AB  - For clinical xenogenic islet transplantation to be successful, several
      requirements must be met. Among them is a sizeable and reliable source of fully
      functional and microbiologically safe islets. The inherent variability among
      porcine pancreases, with respect to islet yield, prompted us to develop a Biopsy
      Score technique to determine the suitability of each pancreas for islet isolation
      processing. The Biopsy Score consists of an assessment of five variables: warm
      ischemia time, pancreas color, fat content, islet size, and islet demarcation,
      each of which is assigned a value of -1 or +1, depending on whether or not the
      established criteria is met. For determination of islet size and demarcation,
      fresh biopsies of porcine pancreases are stained with dithizone (DTZ) solution
      and examined under a dissecting microscope. Based on the scoring of such biopsies
      in pancreases from 26-56-month-old sows, we report here that the presence of
      large (>100 microm diameter), well-demarcated islets in the pancreas biopsy is a
      reliable predictor of isolation success. Encapsulation of the isolated porcine
      islets within the inner layer of a 1.5% agarose and an outer layer of 5.0%
      agarose macrobead, containing 500 equivalent islet number (EIN), provides for
      extended in vitro functional viability (>6 months of insulin production in
      response to glucose), as well as for comprehensive microbiological testing and at
      least partial isolation of the xenogeneic islets from the host immune system. All
      microbiological testing to date has been negative, except for the presence of
      porcine endogenous retrovirus (PERV). Taken together, we believe that the Biopsy
      Score enhancement of our islet isolation technique and our agarose-agarose
      macroencapsulation methodology bring us significantly closer to realizing
      clinical porcine islet xenotransplantation for the treatment of insulin-dependent
      diabetic patients.

PMID- 16285252
TI  - Effect of oxygenated perfluorocarbons on isolated rat pancreatic islets in
      culture.
AB  - One impediment for a wider application of islet transplantation is the limited
      number of donor pancreata for islet isolation. A more efficient utilization of
      available organs could in part alleviate this problem. Perfluorocarbons (PFCs)
      have a high oxygen solubility coefficient and maintain high oxygen partial
      pressures for extended time. They serve also as oxygen "reservoirs" for harvested
      organs in pancreas organ transplantation. The aim of this study was to test
      whether the use of PFCs could also be beneficial for the secretory activity and
      overall viability of cultured purified islets before transplantation. Purified
      rat islets were cultured in static conditions with or without oxygen-saturated
      PFCs for 1 or 7 days. Cell death and apoptosis were assessed by trypan blue
      staining, DNA strand breaks, and caspase 3/7 activity. mRNA levels of insulin and
      ICA512/IA-2, a membrane marker of secretory granules (SGs), were quantitated by
      real-time PCR, whereas insulin content and secretion were measured by RIA.
      Polypyrimidine tract binding protein (PTB), which promotes SG biogenesis, was
      assessed by Western blotting. The number of SGs and the ultrastructural
      appearance of beta5-cells were analyzed by cryoimmunoelectronmicroscopy for
      insulin. Various parameters, including caspase activity, insulin and ICA512/IA-2
      mRNA levels, PTB expression, number of secretory granules, and ultrastructural
      appearance did not significantly differ between control and PFC-cultured islets.
      On the other hand, PFC culture islets showed significantly increased DNA
      fragmentation and a reduced insulin stimulation index at both time points
      compared to control islets. While advantageous for the transport of human
      harvested organs, the use of PFH in the culture may be comparable to and/or not
      provide advantage over conventional protocols for culture of islets for
      transplantation.

PMID- 16285253
TI  - Effects of cryopreservation on cell viability and insulin secretion in a model
      tissue-engineered pancreatic substitute (TEPS).
AB  - The use of encapsulated insulin-secreting cells constitutes a promising approach
      towards the treatment of insulin-dependent diabetes. However, long- term storage
      for off-the-shelf availability still remains an issue, which can be addressed by
      cryopreservation. This study investigated cryopreservation of a model tissue
      engineered pancreatic substitute by two ice-free cryopreservation (vitrification)
      solutions (designated VS55 and PEG400) in comparison to a conventional freezing
      protocol. The model substitute consisted of insulin-secreting mouse insulinoma
      betaTC3 cells entrapped in calcium alginate/poly-L-lysine/alginate (APA) beads.
      Cell viability and static insulin secretion from the thawed cryopreserved groups
      were characterized and compared against fresh controls. Cell viability tests
      using alamarBlue showed that, compared to the fresh groups, the VS55 had the
      highest viability (p < 0.05), followed by both the PEG400 (p < 0.001) and the
      frozen groups (p < 0.001). In response to a square wave of glucose, the static
      insulin secretion data showed that the VS55 and PEG400 groups had similar
      induction levels against the fresh group, whereas the frozen group had the
      poorest secretion rate. Cryosubstitution of capsules showed ice formation in the
      frozen group but no ice in the vitrified groups. Microscopic observations
      revealed holes and/or tears within beads subjected to freezing, whereas no such
      abnormalities were detected in the vitrified samples. Overall, vitrification was
      found to be a promising preservation procedure for this encapsulated cell system.

PMID- 16285254
TI  - Comparative analysis of genetically engineered immunodeficient mouse strains as
      recipients for human myoblast transplantation.
AB  - The development of an optimized animal model for the in vivo analysis of human
      muscle cells remains an important goal in the search of therapy for muscular
      dystrophy. Here we examined the efficiency of human myoblast xenografts in three
      distinct immunodeficient mouse models. We found that different conditioning
      regimes used to provoke host muscle regeneration (i.e., cardiotoxin versus
      cryodamage) had a marked impact on xenograft success. Tibialis anterior muscle of
      Rag2-, Rag-/gammac-, and Rag-/gammac-/C5- mice was treated by cardiotoxin or
      cryodamage, submitted to enzymatic digestion, and analyzed by cytofluorometry to
      quantitate inflammatory cells. Human myoblasts were injected into pretreated
      muscles from immunodeficient recipients and the cell engraftment evaluated by
      immunocytochemistry, 4-8 weeks after transplantation. Donor cell differentiation
      and dispersion within the host muscles was also investigated. Host regeneration
      in cardiotoxin-treated mice was accompanied by a higher inflammatory cell
      infiltration when compared to that induced by cryodamage. Accordingly, when
      compared to the cardiotoxin group, more human myogenic cells were found after
      cryodamage. When the distinct immunodeficient mice were compared, we found that
      the alymphoid strain lacking the complement component C5 (Rag-/gammac-/C5- mice)
      was the most efficient host for human muscle xenografts, when compared with
      C5(+)Rag-/gammac- mice or Rag- mice. Our results demonstrate that cryolesion
      conditioned muscles of Rag-/gammac-/C5- mice provide the best environment for
      long-term in vivo human myoblast differentiation, opening the way for a novel
      approach to study the pathophysiology of human muscle disorders.

PMID- 16285255
TI  - Human serum for culture of articular chondrocytes.
AB  - In the field of cell and tissue engineering, culture expansion of human cells in
      monolayer plays an important part. Traditionally, cell cultures have been
      supplemented with serum to support attachment and proliferation, but serum is a
      potential source of foreign protein contamination and viral protein transmission.
      In this study, we evaluated the use of human serum for experimental human
      articular chondrocyte expansion and to develop a method for preparation of large
      volumes of high-quality human serum from healthy blood donors. Human autologous
      serum contained high levels of epidermal-derived growth factor and platelet
      derived growth factor-AB and supported proliferation up to 7 times higher than
      FCS in primary chondrocyte cultures. By letting the coagulation take place in a
      commercially available transfusion bag overnight, up to 250 ml of growth factor
      rich human serum could be obtained from one donor. The allogenic human serum
      supported high proliferation rate without losing expression of cartilage-specific
      genes. The expanded chondrocytes were able to redifferentiate and form cartilage
      matrix in comparable amounts to autologous serums. In conclusion, the transfusion
      bags allow preparation of large volumes of growth factor-rich human serum with
      the capacity to support in vitro cell expansion. The data further indicate that
      by controlling the coagulation process there are possibilities of optimizing the
      release of growth factors for other emerging cell therapies.

PMID- 16285256
TI  - Age effects on vascular smooth muscle: an engineered tissue approach.
AB  - Tissue engineering of blood vessels offers a potential new therapy for patients
      with vascular occlusive disease. In addition, tissue engineering technologies
      offer the opportunity to study the biology of vascular cells in a biomimetic,
      three-dimensional environment. A model for vascular tissue engineering was used
      to study the effects of vascular cell age on extracellular matrix (ECM)
      deposition, cellular mitosis, and protein synthesis under controlled conditions
      in vitro. Blood vessels were grown using a three-dimensional polyglycolic acid
      (PGA) mesh that was seeded with either infant or adult porcine vascular smooth
      muscle cells. Mechanical forces in the form of pulsatile radial distension were
      applied for the duration of the 7-week growth period. Overall, infant cells
      exhibited higher levels of cellular proliferation, ECM deposition, and remodeling
      activity than cells derived from adult animals. In addition, vessels cultured
      from infant cells had enhanced physical properties compared to vessels cultured
      from adult cells. The differentiation state of the smooth muscle cells in the
      infant and adult constructs was unchanged from the native state. However, the
      levels of immature pro-collagen, although undetectable in the vessels grown from
      adult cells, were similar in native vessels and in vessels grown with infant
      cells. These studies have important implications for the study of aging and
      vascular disease and remodeling, as well as for the field of tissue engineering.

PMID- 16285257
TI  - A simple and highly effective method for the stable transduction of uncultured
      porcine hepatocytes using lentiviral vector.
AB  - Gene therapy is an attractive approach for the treatment of a wide spectrum of
      liver diseases. Lentiviral vectors allow the stable integration of transgenes
      into the genome of nondividing differentiated cells including hepatocytes and
      could provide long-lasting expression of a therapeutic gene. To develop such
      approaches, preclinical studies in large animal models such as pigs are necessary
      to evaluate the feasibility and safety of stable lentiviral integration and long
      term vector expression. In addition, effective lentivector-mediated gene transfer
      onto porcine hepatocytes could advance in cell-based therapies for acute liver
      failure. To investigate this issue, porcine hepatocytes were transduced in
      suspension immediately after their isolation in University of Wisconsin (UW)
      solution containing vitamin E. Up to 80% of hepatocytes stably expressed a GFP
      transgene after a single exposure to lentiviral vector coding for GFP under the
      control of either liver-specific or ubiquitous promoters. Moreover, porcine
      hepatocytes cryopreserved in UW solution containing fetal bovine serum, dimethyl
      sulfoxide, and vitamin E remained highly transducible with lentiviral vector
      after thawing. When thawed, transduced in suspension, and immediately
      transplanted into the spleen of immunodeficient mice, ex vivo lentivirally
      transgene marked xenogeneic hepatocytes were detected in murine liver. We
      demonstrated that porcine hepatocytes are highly susceptible to lentiviral vector
      and describe an easy methodology to efficiently, rapidly, and stably introduce
      transgenes into uncultured porcine hepatocytes.

PMID- 16285258
TI  - Functional characterization of serum-free cultured rat hepatocytes for downstream
      transplantation applications.
AB  - Although ex vivo culture of hepatocytes is known to impair functionality, it may
      still be considered as desirable to propagate or manipulate them in culture prior
      to transplantation into the host liver. The aim of this study was to clarify
      whether rat hepatocytes cultured over different periods of time proliferate and
      retain their hepatocyte-specific functions following transplantation into the
      recipient liver. Rat hepatocytes were cultured under serum-free conditions in the
      presence of hepatocyte and epidermal growth factors. Cells derived from wild-type
      donor livers were transplanted into the livers of CD26-deficient rats. Cell
      proliferation and the expression of hepatocyte-specific markers were determined
      before and after transplantation. Cell number increased threefold over a culture
      period of 10 days. The expression of connexin 32 and phosphoenolpyruvate
      carboxykinase declined over time, indicating the loss of hepatocyte-specific
      functions. Hepatocytes cultured over 4 or 7 days and then transplanted
      proliferated in the host parenchyma. The transplanted cells expressed connexin
      32, cytokeratin 18, and phosphoenolpyruvate carboxykinase, indicating the
      differentiated phenotype. The loss of hepatocyte-specific functions during
      culture may be restored after transplantation, suggesting that the proper
      physiological environment is required to maintain the differentiated phenotype.

PMID- 16285259
TI  - The escape of temperature-sensitive T antigen immortalized rat hepatocytes from
      conditional immortalization.
AB  - Conditionally immortalized hepatocytes (CIH) established with a gene for the
      temperature-sensitive mutant of the T antigen (tsT) have characteristics to stop
      proliferating and to differentiate at nonpermissive temperatures (37-39 degrees
      C) due to inactivation of the T antigen. Therefore, they may be a good
      alternative to primary hepatocytes for experimental investigations or clinical
      applications. Deinduction of the T antigen results in a transient increase of p53
      in these cells, leading to reexpression of normal senescence because of the
      telomere attrition occurring during the early stages of immortalization. To
      determine this T antigen dependency for the maintenance of immortality, a type of
      rat CIH was cultured continuously at 39 degrees C. The frequency of occurrence of
      T-antigen-independent clones ranged from 0.053% to 0.093%. These clones
      maintained the temperature-sensitive property of the T antigen; nevertheless,
      they were able to progress to the S phase and proliferate without undergoing
      apoptosis at 39 degrees C as at 33 degrees C, a permissive temperature. The
      temperature-sensitive point mutation of tsT was not affected in these clones and
      the T antigen was functioning properly. The integrity of the p53 pathway was also
      maintained from the point of Western blot analysis of p21. Although the
      telomerase continued to be expressed and the telomere length was maintained,
      marked chromosomal damage could not be avoided in these cells. It is a plausible
      explanation that this escape phenomenon from conditional immortalization may be
      related to the change of other genes involved in cell cycles, which have yet to
      be elucidated. In conclusion, CIH could lose their temperature-sensitive
      characteristics without the change of tsT, itself, and the T antigen is not
      always necessary to maintain their immortality. Therefore, the results obtained
      from experimental investigations using these cells should be interpreted
      carefully, and unpredictable phenotypic changes should also be taken into
      consideration when using them in clinical applications.

PMID- 16285260
TI  - Illustrated keys to the mosquitoes of Thailand. II. Genera Culex and Lutzia.
AB  - Illustrated keys for the identification of the fourth-instar larvae and adult
      females of the mosquito genera Culex and Lutzia is presented, along with
      information on the geographic distribution of each species, and bionomics. Eighty
      two species belonging to subgenera Culex, Culiciomyia, Eumelanomyia,
      Lophoceraomyia, and Oculeomyia of genus Culex, and three species belonging to
      subgenus Metalutzia of genus Lutzia are recognized in Thailand. Subgenus
      Oculeomyia includes a probable new species near Cx. infula and Lt. vorax is
      recognized as a new country record.

PMID- 16285261
TI  - Outbreak of Ebola haemorrhagic fever in Yambio, south Sudan, April - June 2004.

PMID- 16285262
TI  - Use of silicone hearing aid mold material in laryngotracheal reconstruction.
AB  - OBJECTIVES: Endolaryngeal stenting in patients with irregularly shaped larynges
      can be challenging. In such cases, the use of a moldable yet reasonably rigid
      endolaryngeal stent is desirable. The purpose of this report is to describe our
      experience with silicone hearing aid material as a moldable endolaryngeal stent
      in a patient with an atypically shaped larynx. METHODS: A patient with relapsing
      polychondritis that resulted in complete stenosis of the subglottic airway
      underwent laryngotracheal reconstruction. Moldable silicone, commonly used to
      prepare ear canal molds for hearing aids, was molded into the neo-endolarynx to
      serve as a custom-made endolaryngeal stent. RESULTS: The patient tolerated the
      moldable silicone stent well and had a patent airway with epithelialization 8
      months after removal. CONCLUSIONS: Silicone mold material is a suitable substance
      for endolaryngeal stenting. It conforms to the configuration of the individual's
      airway, is tolerated well, can be removed relatively easily, and is a useful
      alternative to prefabricated stents in laryngotracheal reconstruction.

PMID- 16285263
TI  - Decannulation and outcome following pediatric tracheostomy.
AB  - OBJECTIVES: We investigated the long-term outcome of pediatric tracheostomy to
      identify predictive factors of early decannulation. METHODS: We performed a
      retrospective chart review of a consecutive series of 75 patients less than 20
      years of age who underwent tracheostomy between 1998 and 2003 during their
      admission in a tertiary pediatric institution. Complete information was available
      on 65 patients. RESULTS: There were 41 male patients and 24 female patients
      (median age, 7 months). The indications for tracheostomy were an obstructed
      airway in 36 patients, prolonged mechanical ventilation in 15, and
      tracheobronchial toilet or aspiration risk in 14. Twelve patients died, and 30 of
      the 53 survivors were decannulated (median cannulation time, 123.5 days).
      Additional airway procedures were required for decannulation in those with
      obstructed airways. Patients who had tracheostomy performed for tracheobronchial
      toilet had a significantly shorter cannulation time than those with the other two
      indications (log-rank test, chi2(2) = 47.11; p < .00001). Patient diagnosis was
      also a significant predictor of cannulation time (log-rank test, chi2(2) = 66.05;
      p < .00001). Tracheobronchial toilet as a tracheostomy indication and both trauma
      and neurologic conditions as admission diagnoses were statistically significant
      independent variables that predicted earlier decannulation on multivariate
      analysis. Analysis of other group variables--age, sex, and tracheostomy insertion
      technique--did not reveal any significant difference in cannulation times.
      CONCLUSIONS: Tracheostomy indication and patient diagnosis are significant
      variables that predict early decannulation in pediatric patients in whom
      tracheostomy is required. Other variables were not shown to be significant
      independent predictors.

PMID- 16285264
TI  - Hemorrhage following coblation tonsillectomy.
AB  - OBJECTIVES: We performed a prospective study to evaluate the incidence of post
      tonsillectomy hemorrhage (PTH) in adults and children who underwent Coblation
      tonsillectomy (CTE) under general anesthesia. METHODS: The data of 63 adults and
      children (mean age, 21.8 years) were analyzed. RESULTS: There were 7 episodes of
      considerable bleeding (11.1%) that required surgical treatment under general
      anesthesia in 6 patients, of whom 5 experienced secondary bleeding (>24 hours).
      Moreover, bleeding and massive swelling of the pharynx required surgical
      treatment and prolonged intubation (35 hours) in 1 patient. None of the patients
      received blood transfusions. There was no case with a lethal outcome. Less
      intense bleeding (clots; blood-tinged sputum) was observed in 17 patients (27%)
      who required readmission or prolonged inpatient observation, 1 of whom had
      previously undergone surgical treatment of PTH. However, these 17 patients had an
      uneventful clinical course. In total, 22 patients experienced minor or major
      forms of PTH (34.9%). CONCLUSIONS: At least in our hands, CTE dramatically
      increased the frequency of PTH. The high rate of secondary bleeding contrasts
      with our documented experience using conventional methods, ie, cold dissection
      and suture ligation, to achieve hemostasis (7.9% with CTE versus <0.8% with
      conventional methods). Therefore, at our institution, tonsillectomy with
      conventional instruments remains the method of choice.

PMID- 16285265
TI  - Inside-out complete tonsillectomy: extended intracapsular tonsillectomy for
      severe sore throat.
AB  - OBJECTIVES: This consecutive case series is presented to describe inside-out
      complete tonsillectomy and to assess its effects on postoperative pain and
      bleeding and its initial effectiveness in controlling recurrent sore throat and
      peritonsillar abscess formation. METHODS: Bipolar electrosurgical scissors are
      used for bloodless resection of 90% of the tonsillar mass. During controlled
      resection, tonsil tissue is intentionally left at the superior and inferior poles
      and at the deepest part of the tonsillar fossa to provide coverage for nutrient
      arteries and the tonsillar plexus of veins. This tissue is then electrodesiccated
      and removed under direct vision and indirect mirror guidance to achieve complete
      tonsillectomy. RESULTS: One hundred eighty-three consecutive tonsillectomies were
      performed by a single surgeon in a 16-month period, 47 of which were for the
      indication of recurrent sore throat (44) or recurrent peritonsillar abscess (3).
      Among these 47 children, there were 2 readmissions for dehydration. There were no
      immediate or delayed bleeding episodes. The average child required 4 days of
      narcotic pain medication. The mean annualized number of severe sore throats
      decreased from 5.24 before operation to 0.36 after operation (p < .0001,
      Student's paired t-test). There were no recurrent peritonsillar abscesses.
      CONCLUSIONS: Inside-out complete tonsillectomy achieves the surgical goal of
      complete tonsillectomy with the smallest possible wound and minimal injury to the
      surrounding tissue. The perioperative morbidity is markedly decreased compared to
      that of historical controls. The initial results suggest effectiveness similar to
      that of extracapsular tonsillectomy.

PMID- 16285266
TI  - Relationship of snoring and sleepiness as presenting symptoms in a sleep clinic
      population.
AB  - OBJECTIVES: Sleepiness has traditionally been considered medically the cardinal
      symptom of obstructive sleep apnea syndrome. Snoring is perceived as a social or
      cosmetic complaint. Without independent medical morbidity, snoring identification
      and treatment is not a major focus in sleep medicine. We speculate that snoring
      is a major independent symptom. To evaluate how patients rated snoring symptom
      severity, we compared the relative significance of a sleep clinic population's
      presenting symptoms of snoring and sleepiness. METHODS: We performed a
      retrospective analysis of 770 consecutive patients who completed sleep intake
      evaluation forms at the initial clinic visit, including standardized forms for
      both sleepiness and snoring using previously validated visual analog scales. Data
      on symptom magnitude (scale of 1 to 10), symptom importance (scale of 1 to 5), a
      combined symptom product score consisting of magnitude multiplied by importance
      (MIP; scale of 1 to 50), the Epworth Sleepiness Scale (ESS; n = 599), and the
      apnea-hypopnea index (AHI; n = 482; mean +/- SD, 35.6 +/- 31.9 events per hour)
      were collected. RESULTS: The mean snoring measures (magnitude, importance, and
      MIP) were greater than those for sleepiness (MIPsnoring of 32.7 +/- 14.8 versus
      MIPsleepiness of 22.4 +/- 14.2, p < .001). Snoring scored higher than sleepiness
      in 72% of individuals. To assess whether sleep apnea or sleepiness severity
      affected symptom scores, we stratified the subgroup with sleep studies into
      quartiles by AHI and ESS score. Snoring consistently scored higher than
      sleepiness in most AHI and ESS quartiles (p < .01). Only in the most severe ESS
      quartile did any sleepiness measure (importance) score higher than the snoring
      measure (p < .05). CONCLUSIONS: The presenting symptoms of snoring are larger in
      magnitude, importance, and severity than those of sleepiness in a broad
      population of patients with sleep disorders and sleep-disordered breathing
      irrespective of severity of sleep apnea or sleepiness. Symptoms of major
      significance are clinically relevant to identifying, diagnosing, and treating
      patients. Failure of medical providers to appreciate the impact of snoring on
      this population may affect attempts to identify, diagnose, and treat patients
      with sleep-disordered breathing.

PMID- 16285267
TI  - Study of cyfra 21-1, a tumor marker, in head and neck squamous cell carcinoma.
AB  - OBJECTIVES: We performed a prospective study to determine the cutoff value and
      the prognostic value of Cyfra 21-1, a serum tumor marker, in head and neck
      squamous cell carcinoma (HNSCC). METHODS: The serum concentration of Cyfra 21-1
      was measured in a group of 300 patients (group 1) with HNSCC, in a control group
      of 71 healthy subjects (group 2), and in a group of 73 patients with a
      nonmalignant tumor or inflammatory disease (group 3). The concentrations were
      compared between the various groups and subgroups; the cutoff value was
      calculated with a receiver operating characteristic curve. Furthermore, the serum
      concentrations of Cyfra 21-1 before treatment in the group of 300 patients were
      compared with the stage of the disease and with the evolution of the overall
      survival rate and the disease-free survival rate. Finally, to determine whether
      Cyfra 21-1 is an independent prognostic factor, we compared the concentrations,
      by a Cox model, with the classic prognostic factors of HNSCC. RESULTS: At the
      cutoff value of 1 ng/mL, the specificity was 94% and the sensitivity was 72%. The
      serum concentrations of Cyfra 21-1 were statistically correlated with the stage
      of the disease. The overall survival rate and the disease-free survival rate were
      lower in patients with high serum concentrations, and these differences were
      statistically significant (p < .001). The Cox model allows us to conclude that
      Cyfra 21-1 is a prognostic marker that is independent of other classic prognostic
      factors. CONCLUSIONS: Cyfra 21-1 is an interesting tumor marker that could be
      proposed for the early detection of HNSCC with a cutoff value of 1 ng/mL.
      Furthermore, Cyfra 21-1 can be considered an independent prognostic marker.

PMID- 16285268
TI  - Angular vestibulo-ocular reflex gains correlate with vertigo control after
      intratympanic gentamicin treatment for Meniere's disease.
AB  - OBJECTIVES: The objective of our study was to determine whether angular vestibulo
      ocular reflex (aVOR) gains correlated with vertigo control after intratympanic
      gentamicin treatment for Meniere's disease. METHODS: We conducted a prospective
      study of 18 subjects with unilateral Meniere's disease treated with intratympanic
      gentamicin injection and followed all subjects for 1 year. We measured the gain
      of the aVOR elicited by rapid rotary head thrusts in each of the canal planes for
      each subject before and after treatment with intratympanic gentamicin by using
      magnetic search coils to record eye movements. RESULTS: During the follow-up
      period, 11 subjects ("single-treatment group"; 61%) had control of their vertigo
      with a single gentamicin injection. The remaining 7 subjects ("multiple-treatment
      group"; 39%) experienced recurrent vertigo that required a second injection of
      gentamicin at a mean of 6 months after the first treatment. The 11 subjects in
      the single-treatment group had significantly greater reduction of labyrinthine
      function after the first treatment, as measured by change in ipsilateral
      horizontal canal gain, than did the 7 subjects with vertigo recurrence. Changes
      in caloric asymmetry did not correlate with vertigo control. CONCLUSIONS: Our
      results suggest that successful treatment of Meniere's disease is closely related
      to attenuation of semicircular canal function as measured by horizontal canal
      aVOR gains.

PMID- 16285269
TI  - Prognosis of inner ear periphery and central vestibular plasticity in sudden
      deafness with vertigo.
AB  - OBJECTIVES: We sought to elucidate the clinical problems and otopathology of
      patients with sudden deafness with vertigo (SDV). METHODS: In 24 patients with
      SDV who had significant canal paresis (CP) at their first visit to our hospital
      between 1997 and 2001, we examined pure tone audiograms, caloric tests, and
      several questionnaires twice, at the first visit within 5 days after the onset
      and around 2 years after steroid therapy. RESULTS: These examinations revealed
      that improvements of auditory and vestibular function in patients with SDV tended
      to be correlated with one another. Sixteen of the 24 patients (66.7%) still had
      CP. This rate in SDV was significantly worse than that reported previously for
      vestibular neuritis (VN). On the other hand, patients with SDV with long-lasting
      CP had a faster reduction of head-shaking afternystagmus and of handicaps in
      their everyday life due to dizziness than did patients with VN and CP.
      CONCLUSIONS: These findings suggest that SDV may deteriorate the inner ear
      function more severely but accelerate the central vestibular compensation more
      effectively than VN after the lesion. It is well known that vestibular neurectomy
      causes much more severe motion-induced dizziness after surgery than does
      labyrinthectomy. Taken together, these findings suggest different regions of
      damage in SDV (mainly the labyrinth, as in labyrinthectomy) and VN (mainly the
      ganglion, as in vestibular neurectomy).

PMID- 16285270
TI  - Phonetic effects of paralytic dysphonia.
AB  - OBJECTIVES: This study was performed to determine whether and how unilateral
      vocal fold paralysis (UVFP) affects the production and perception of voiced stop
      consonants as compared with unvoiced stops, and to analyze the phonetic effects
      of UVFP on the voicing feature. METHODS: Phonetic constructs pronounced by 7 male
      patients with UVFP and 5 normal male subjects were recorded. The 432 speech
      tokens consisted of intervocalic, prevocalic, and postvocalic stop consonants
      (/p/, /t/, /k/, /b/, /d/, /g/) in the vowel contexts /a/ and /i/. Perceptual
      consonant identification testing was performed with 5 voice and speech
      professionals as listeners. The type and frequency of errors made in consonant
      identification were analyzed. Spectrographic analysis was used to analyze
      acoustic cues. RESULTS: The rate of correct consonant identification was
      significantly lower for tokens pronounced by patients with UVFP (77.3% versus
      97.6%, p = .0001) because of incorrect identification of the voiced consonants,
      frequently perceived as their unvoiced homologues. Confusion between dental and
      alveolar place of articulation for unvoiced stops was also noted. CONCLUSIONS:
      Unilateral vocal fold paralysis alters the voiced-unvoiced stop consonant
      distinction and the dental-palatal stop consonant distinction in an experimental
      nonspeech context. This finding implies the existence of a phonetic handicap for
      patients with UVFP. Further studies should determine the effects of UVFP on
      global speech intelligibility.

PMID- 16285271
TI  - Alterations in contractile properties of tongue muscles in old rats.
AB  - OBJECTIVES: Fatigue and weakness are well-known signs of aging that are related
      to sarcopenia, or loss of skeletal muscle mass, organization, and strength.
      Sarcopenia may affect swallowing. The tongue plays a vital role in swallowing,
      but there is limited knowledge regarding age-related changes in lingual muscle
      contractile properties. Our purpose was to determine whether alterations in
      tongue force, temporal features of tongue muscle contraction, and fatigability
      are manifested as a function of aging in old rats. METHODS: We evaluated tongue
      muscle contractile properties in young and old Fischer 344/Brown Norway rats.
      Contractions were elicited via bilateral electrical stimulation of the
      hypoglossal nerves. RESULTS: Maximum tongue forces and fatigability were not
      significantly altered in old animals, but aging was associated with significantly
      longer twitch contraction time and longer half-decay recovery time intervals (p <
      .01). CONCLUSIONS: The results indicated that old animals generated sufficient
      maximum tongue forces, but were slower in achieving these forces than young
      animals. These findings are consistent with reports of altered temporal
      parameters of tongue actions during swallowing in humans, and suggest that a
      disruption in the timing of muscle contraction onset and recovery may contribute
      to the altered tongue kinetics observed with aging.

PMID- 16285272
TI  - Nitrotyrosine in otitis media with effusion.
AB  - OBJECTIVES: Our purpose was to investigate mucosal cell injury due to the nitric
      oxide (NO)-superoxide system in otitis media with effusion. METHODS: We
      determined the levels of nitrotyrosine (NT) and NO and the activities of
      superoxide dismutase (SOD) and lactic dehydrogenase (LDH) in 90 middle ear fluid
      samples. RESULTS: The NT concentration was significantly higher in group A (<16
      years old) than in group C (>50 years old; p < .05), and significantly higher in
      the acute group than in the chronic group (p < .05). The NO concentration did not
      show a significant difference among the groups. The activity of SOD showed
      significant correlations with the concentrations of NT and NO and with LDH
      activity (p < .05). The LDH activity was significantly greater in group A than in
      group C (p < .05). CONCLUSIONS: Our results indicate involvement of the NO
      superoxide system in the pathogenesis of otitis media with effusion, showing
      evidence of protein and/or cell injury in the middle ear.

PMID- 16285273
TI  - Individual subject laryngeal dimensions of multiple mammalian species for
      biomechanical models.
AB  - OBJECTIVES: This report provides a detailed knowledge base of individual subject
      laryngeal cartilage dimensions across multiple species to assist researchers in
      creating subject-specific biomechanical laryngeal models. METHODS: The raw data
      from previous laryngeal cartilage studies were grouped by species (for human,
      canine, and ovine) and by cartilage (arytenoid, thyroid, and cricoid) by means of
      a previously reported labeling scheme. No animals were sacrificed specifically
      for the present study. RESULTS: More than 1,500 measurements from 37 subjects are
      presented in 15 tables. No comparisons of the average measures were attempted, as
      they were done in previous studies. CONCLUSIONS: By means of a database of
      individual subject dimensions, a laryngeal model could be designed and tested to
      morph from one subject to the next, predicting subject-specific results of
      laryngeal function. Eventually, this would lead to modeling patient-specific
      laryngeal disorders and the prediction of therapeutic outcomes. An electronic
      downloadable version of the database is made available to assist in this effort.

PMID- 16285274
TI  - [Well established?].

PMID- 16285275
TI  - [Dithranol in the treatment of scalp psoriasis].
AB  - Dithranol in its usual petrolatum base cannot be effectively applied to the
      scalp. The washable cream base is not often employed in Germany, both because
      this form of application is not well-known and because the positive effects are
      underestimated while the adverse effects are overestimated. Therefore we have
      searched the literature for appropriate studies, application recommendations and
      reports on side effects. We list scalp preparations containing dithranol
      available in neighbouring European countries together with recommendations and
      warning notes. Since the dithranol molecule contains hydrophilic and lipophilic
      parts, it can be easily incorporated into soaps. The stability of such
      preparations is limited; their effectiveness is supported by the usage of
      dithranol in an emulsifying oil base in the Charite Department of Dermatology for
      more than twenty years. The special vehicle used, bio-wash-oil, is an oily fluid
      soap which was designed for cleaning the heavily soiled hands of factory workers.
      It can be easily applied to the scalp and washed off with water. Here we re
      examine the original study on dithranol in bio-wash-oil published by Meffert et
      al. in 1979, summarize our subsequent experience and present a recent comparative
      study paying special attention to side effects, practical notes, and patient
      comfort and satisfaction.

PMID- 16285278
TI  - [Evaluation of the external tissue extender (Ete) in secondary wound closure].
AB  - BACKGROUND: For surgical closure of large skin defects, elaborate reconstructive
      plastic surgery or other methods such as internal subcutaneous balloon tissue
      expanders are required in order to avoid tension on the closure margins. Here we
      point to the benefits and disadvantages of an improved and simple method of
      secondary wound closure by secondary sutures. PATIENTS AND METHODS: We employed a
      system called External Tissue Extender (ETE), which consists of silicone strings
      and plastic stoppers pulling the corresponding surgical sites together and evenly
      distributing the tension. Possible indications in dermatologic surgery and our
      experiences with this technique are outlined. RESULTS: Implantation and handling
      of the ETE are very easy and fast. The functional results are good and the
      cosmetic outcome satisfactory. More invasive surgical procedures can be avoided
      by using this method. A major disadvantage is the possibility of developing
      necrosis under the plastic stoppers. CONCLUSION: According to our experience, the
      ETE is a useful alternative indicated in certain dermatosurgical situations.

PMID- 16285276
TI  - [Systemic treatment of cutaneous lupus erythematosus].
AB  - The treatment of cutaneous lupus erythematosus (CLE) remains a therapeutic
      challenge. In many cases, systemic treatment of the disease is necessary,
      especially in cases resistant to topical treatment or with internal organ
      involvement. Even though many different agents can be employed in this situation,
      most are not approved in Germany for the treatment of CLE. We give an overview of
      the agents used in the systemic treatment of CLE and review their mechanisms of
      action, indications and their practical use in cutaneous LE based on literature
      results and our own experience. We discuss corticosteroids, antimalarials,
      dapsone, azathioprine, cyclophosphamide, methotrexate, retinoids, cyclosporine A,
      mycophenolate mofetil, sulfasalazine, thalidomide, clofazimine, tacrolimus,
      immunoglobulins, monoclonal antibodies, plasmapheresis, etanercept, infliximab,
      feflunomid, gold and interferon-alpha.

PMID- 16285277
TI  - [Therapy of pruritus associated with skin diseases with the serotonin receptor
      antagonist ondansetron].
AB  - BACKGROUND: Pruritus is often a stressing symptom and a therapeutic challenge. We
      report our experience with the serotonin receptor antagonist ondansetron in the
      symptomatic treatment of pruritus accompanying various skin diseases. PATIENTS
      AND METHODS: The influence of ondansetron (8-12 mg orally per day) on pruritus
      was assessed in twelve patients with various skin disorders. The intensity of
      pruritus was quantitated daily by a visual analogue scale over the time period of
      one week before, during, and one week after treatment. RESULTS: Ondansetron
      decreased pruritus intensity in prurigo simplex (four patients), asteatotic
      eczema (two patients), parapsoriasis en plaques, and pruritus of unknown origin
      (one patient each). One of two patients with atopic dermatitis experienced
      relief, whereas no benefit was observed in urticaria factitia and notalgia
      paraesthetica (one patient each). CONCLUSIONS: Ondansetron may ameliorate the
      concomitant pruritus of some dermatologic diseases.

PMID- 16285279
TI  - [Systemic contact eczema against Balsam of Peru].
AB  - Balsam of Peru (PB; Myroxylon pereirae) is a natural product derived from resin
      of a tropical tree (MyroxyIon balsamum (L.) Harms var. pereirae (Royle) Baillon).
      Because of its antiseptic and aromatic properties PB or PB-components can be
      found worldwide not only in many health care and cosmetic products, but also in
      food items and semiluxury food. PB contains a wide variety of potent contact
      allergens leading to hypersensitivity reactions not only after topical
      application but also oral uptake. We report a 51-year-old brewer with chronic
      eczema of the hands who showed delayed-type patch test reactions against PB and
      fragrance-mix. Oral PB-challenge led to exacerbation of the eczema 5 and in a
      repeated test 2 days later. We here review this probably quite often overlooked
      disease and the therapeutic consequences which require profound knowledge about
      the wide distribution of PB when advising the patient about a PB-restricted diet.
      In addition, this unusual case report demonstrates that one has to consider
      marked delayed hypersensitivity reaction when investigating a systemic contact
      allergy.

PMID- 16285281
TI  - [The Langerhans cell histiocytoses].

PMID- 16285280
TI  - [Scabies triggering Darier's disease].
AB  - An increased incidence of scabies has been noted in many countries. Difficulties
      may arise when unrecognized infestations trigger or aggravate other
      dermatological disorders. We present an instructive case of Darier's disease,
      which did not respond to appropriate therapy regimens due to constant triggering
      by an undetected underlying scabies infestation. In this case, a 44-year-old
      Italian man presented with typical symptoms of Darier's disease. In addition, the
      patient reported massive pruritus, which is rather uncommon in this disorder. The
      disease proved recalcitrant to established treatment regimens resulting in
      excessive treatment costs. We confirmed the diagnosis of Darier's disease by
      histopathological analysis, and, in addition, detected arthropod fragments in the
      upper epidermis. Systemic ivermectin and topical allethrin followed by acitretin
      and PUVA-bath therapy resulted in rapid improvement of the debilitating pruritus
      as well as alleviation of the symptoms of Darier's disease.

PMID- 16285282
TI  - [Young man with verrucous heel tumor ].

PMID- 16285283
TI  - [Hemorrhages in the fingers of a 45-year-old woman].

PMID- 16285284
TI  - [Pilonidal sinus. Stage 2].

PMID- 16285285
TI  - [Professor Brunello Wuthrich -- the 65th birthday].

PMID- 16285286
TI  - [Please come in, dear readers!].

PMID- 16285287
TI  - [How does eczema arise?].
AB  - New experimental results on the role of T cells and keratinocytes have led to a
      better understanding of eczematous inflammation and can help explain both the
      clinical and histological pictures of eczema. Besides activated endothelial cells
      and adhesion molecules, a complex interaction of numerous chemokines controls the
      recruitment of T cells from the blood vessels and their migration into the dermis
      and epidermis. Activated T cells damage the epidermis by pro-inflammatory
      cytokines and can induce apoptosis of individual keratinocytes through "killer
      molecules". Cleavage of adhesion molecules on keratinocytes leads to spongiotic
      changes. Keratinocytes then activate repair mechanisms, which cause acanthosis
      and parakeratosis in chronic eczema.

PMID- 16285288
TI  - [New developments in the systemic treatment of psoriasis].
AB  - The current standard systemic therapeutic modalities for psoriasis have many
      potential side effects. Progress made in the understanding of the pathophysiology
      of psoriasis as a T-cell-mediated dermatosis provide options for new more precise
      therapeutic approaches. These immunological therapeutic strategies involve the
      inhibition/depletion of activated T-lymphocytes, the inhibition of antigen
      presentation and thus the regulation of T-cell activation, the inhibition of
      adhesion of inflammatory cells, the inhibition of effects of proinflammatory
      mediators and the administration of antiinflammatory cytokines. This article
      summarizes these new systemic therapeutic approaches. Clinical results in the
      early studies have been mixed. In the next years further results of phase II- and
      phase Ill-studies may be expected, which should allow better assessment of the
      potential of those particular approaches. Some of these approaches could lead to
      the approval of new drugs to treat psoriasis and to enhance or replace already
      existing therapeutic options. Furthermore results of therapeutic experiments
      should contribute to a better understanding of the disease. As we learn which
      mechanisms are more or less important for the disease, we will be better able to
      plan intervention strategies.

PMID- 16285289
TI  - [Trichoteiromania].
AB  - BACKGROUND: The physical influences leading to traumatic hair injury may be the
      result of cosmetic treatments, may be accidental or self-inflicted. The most
      frequent cause of self-inflected hair loss is trichotillomania, in which the hair
      is plucked, while trichotemnomania, in which the hair is deliberately cut, is
      less frequent. Freyschmidt-Paul et al. proposed the term trichoteiromania for yet
      another type of artificial hair loss, which results from perpetual rubbing of the
      scalp with fracturing of the hair shafts. PATIENTS AND METHODS: Four patients
      with trichoteiromania are further characterized on the basis of clinical,
      morphological and psychopathological criteria. RESULTS: In contrast to
      trichotillomania, trichoteiromania has no diagnostic histopathological features
      and has a normal trichogram. Traumatic changes to the hair shaft are more
      conspicuous, with splitting at the ends of the hairs, giving the impression of
      white tips. The underlying mental disorder varis among the patients, though scalp
      dysaesthesia, not explained through any specific dermatological disorder, is a
      common denominator in all cases. CONCLUSIONS: While trichotillomania is
      considered to be an obsessive-compulsive disorder, the underlying mental disorder
      in trichoteiromania represents a more heterogeneous group. Cooperation with the
      psychiatrist is indicated, as much as the management and prognosis of
      trichoteiromania will depend on recognition of the underlying mental disorder and
      its specific psychotherapeutic and pharmacological treatment.

PMID- 16285290
TI  - Treatment of scleromyxoedema with hydroxychloroquine.
AB  - BACKGROUND: Scleromyxoedema is a rare disease of unknown aetiology that is
      characterized by deposition of mucin and sclerotic induration of the skin; it is
      associated with paraproteinaemia. Patients suffer from progressive disability due
      to immobilization and cosmetic disfigurement. Treatment of scleromyxoedema is a
      therapeutic challenge. The antimalarial hydroxychloroquine has a rapid and
      reliable effect in reticular erythematous mucinosis. PATIENTS AND METHODS: Four
      consecutive patients (two women, two men; median age: 50 years) with
      scleromyxoedema, three of them with IgG lambda paraprotein, were treated with
      hydroxychloroquine. Treatment was initiated with 600 mg p.o. for 10 days,
      followed by 400 mg for at least 4 weeks, and 200 mg thereafter. RESULTS: Complete
      remission of skin manifestations was achieved in one patient, whereas three
      patients achieved a partial remission of 61+, 5 and 25 months' duration. Notably,
      three patients felt increased mobility and reduced firmness of skin during the
      first week of treatment, which was reflected in a rapid reduction in dermal
      thickness. In one patient, dysphagia was reverted as evidenced by normalization
      of oesophageal clearance. Paraproteinaemia was not influenced at all. Side
      effects included one case of electroretinogram abnormalities after 19 months of
      therapy and one case of leucopenia after 3 months. CONCLUSION: Hydroxychloroquine
      is an effective form of therapy for scleromyxoedema, leading to rapid and
      prolonged alleviation of symptoms.

PMID- 16285292
TI  - [Pseudomelanoma following laser treatment or laser-treated melanoma?].
AB  - BACKGROUND: The increasing use of lasers for the removal of pigmented skin
      lesions has led to a growing risk of erroneously treated malignant melanocytic
      tumours. PATIENTS AND METHODS: In two patients, both of whom developed a
      melanoma, the lesions were initially misdiagnosed clinically as a benign naevus
      and treated with laser vaporisation. RESULTS: On recurrence of the tumours, the
      diagnosis of melanoma was finally established by histological examination of the
      excised tumours in which differentiation from pseudomelanoma remained difficult.
      CONCLUSIONS: In such cases of initially misdiagnosed melanomas, laser removal not
      only complicates and delays the correct diagnosis but might also worsen the
      prognosis after recurrence of an incompletely removed tumour.

PMID- 16285291
TI  - [DRGs in dermatology: quality of coding and the effects of case mix].
AB  - BACKGROUND: High-quality coding of patient clinical data is mandatory for an
      effective DRG classification to result in adequate allocation of funding for
      inpatient treatment. The aim of the study was to determine the effect of
      controlled documentation on patient clinical data and to ascertain the outcome of
      calculated DRG-based yields depending on higher coding quality of patient
      treatment. PATIENTS AND METHODS: In a prospective study, 1914 patient clinical
      records from the Department of Dermatology, University of Muenster, were captured
      using different documentation standards and the data was analysed. Grouping was
      performed on the basis of the Australian Refined DRG system v4.1. Dermatological
      patients were broken down into eleven groups based on principle diagnosis.
      RESULTS: As a result of a controlled documentation, case mix, case mix index and
      patient clinical complexity level (PCCL) value were increased within identical
      samples. Furthermore, it was shown that high-quality coding may result in exact
      and reasonable classification of patient clinical data. CONCLUSIONS: Different
      documentation standards may cause undesired effects on the monetary yields of in
      patient treatment. It appears that high-quality coding and controlled
      documentation may guarantee adequate yields. FauIty. incomplete and (up)coding
      could be a potential economic risk for hospitals.

PMID- 16285293
TI  - [Junctional epidermolysis bullosa non-Herlitz with urethral affection].
AB  - Epidermolysis bullosa (EB), a hereditary, blistering form of dermatosis, can be
      divided into the following three main groups: epidermolysis bullosa simplex
      (EBS), junctional epidermolysis bullosa (JEB) and dystrophic epidermolysis
      bullosa (DEB). The previously known form of generalized atrophic benign
      epidermolysis bullosa (GABEB) is classified as junctional epidermolysis bullosa
      non-Herlitz (JEB-nH) today. An 11-year-old boy with junctional epidermolysis
      bullosa non-Herlitz with urethal involvement had a complicated course with
      bladder obstruction and secondary renal insufficiency. According to currently
      available literature, this is the earliest case known of JEB-nH with involvement
      of the urinary tract in childhood. Taking into account the complicated course in
      this young patient, it must be emphasized that in cases of epidermolysis bullosa
      hereditaria, uncommon affections occurring in infancy should be given careful
      attention, as such types of associated manifestations are mainly responsible for
      the lethality in this disease.

PMID- 16285294
TI  - [Chronic venous venous ulcus cruris. Pathogenesis and the significance of
      "aggressive micro-milieus"].

PMID- 16285295
TI  - [Ulcer on the corner of the mouth of the in a 19-year old male patient].

PMID- 16285296
TI  - [Onychomycoses. Version from 21.1.1997, edited and completed on 5 April 2002,
      valid until 31.12.2005].

PMID- 16285297
TI  - [Galderma relies on partnerships].

PMID- 16285298
TI  - [Revered DDG members, my dear colleagues ].

PMID- 16285299
TI  - [Analysing strengths and weaknesses: opportunities and threats for service
      providers in the German health care system].
AB  - Hospitals in the German health care system are confronted with increasing
      economic competition due to paradigm shifts in funding inpatient treatment. Major
      hospitals, such as university hospitals, will be under significantly greater
      pressure to keep up the ability to compete by uniform per case payment. The new
      hospital funding system based on a Diagnosis Related Group (DRG) system and the
      economic competition involved require analyses of organisational and locational
      factors. Cooperativeness and efficient utilisation of resources, properties and
      staff will be determining factors to secure existence. Adequate responses and
      strategies are essential to cope with the growing operating requirements.
      Carrying out an analysis identifying one's own strengths and weaknesses,
      opportunities and threats will help to focus activities and sustainable
      strategies into areas where the strengths and the greatest opportunities lie. An
      example of the process of strategic planning and positioning is shown for a
      university department of dermatology.

PMID- 16285300
TI  - [Beyond glucocorticoids, retinoids and vitamin D--the evolution of nuclear
      hormone type transcription factor targeting in the skin].
AB  - Nuclear hormone receptors are ligand-dependent transcription factors. The class
      of nuclear hormone receptors that form heterodimers with retinoid X receptor
      includes members that are well established targets of current dermatological
      therapeutics such as the retinoic acid receptor (RAR) and the vitamin D receptor
      (VDR) as well as more recently discovered receptors including the peroxisome
      proliferator-activated receptors (PPAR) and the liver X receptor (LXR). After
      ligand activation (often lipid metabolites), these intracellular receptors exert
      their functions by binding to specific response elements in regulatory sequences
      of target genes, preferentially those involved in differentiation, energy
      expenditure and lipid metabolism. A number of selective activators has been
      developed by combinational chemistry, initially for their anti-diabetic and lipid
      lowering properties as well as their ability to regulate bile acid and drug
      metabolism. However, these activators also have marked effects on cutaneous
      homeostasis. Therefore, these compounds have important implications for
      dermatological therapy. In this review, the clinical implications of the more
      recently discovered members of the nuclear hormone receptor family are discussed.

PMID- 16285301
TI  - Cytogenetic comparison between clear cell sarcoma and a case of acral clear cell
      melanoma.
AB  - BACKGROUND: Clear cell melanoma is a recently described variant of melanoma
      characterized by prominent clear cell features similar to clear cell sarcoma.
      PATIENTS AND METHODS: The present report describes a deeply invasive case of
      clear cell melanoma clinically, histologically, immunohistochemically,
      ultrastructurally and with the FISH technique and compares these findings with
      those in clear cell sarcoma. RESULTS: A 68-year-old male presented with an
      ulcerated, deeply invasive melanoma on the heel, corresponding to Clark level V,
      with a maximum tumour thickness of more than 14 mm; follow-up revealed inguinal
      lymph-node and lung metastases. Apart from characteristic histological features
      of melanoma with intraepidermal involvement, the lesion was immunohistochemically
      positive for 5100 protein, with HMB45 and A103 (anti-human Melan-A/MART-1), and
      ultrastructurally showed melanosomes. In deeply invasive parts, the lesion was
      indistinguishable from clear cell sarcoma, exhibiting nests, fascicles and sheets
      of pale-staining epithelioid to spindle-shaped cells ('clear cells') with
      scattered Touton-like multinucleated giant cells. Cytogenetic analysis using the
      FISH technique revealed a 12q13 chromosomal break in the vicinity of the ATFI
      gene but without ATF1 disruption. CONCLUSION: These findings may indicate the
      possible involvement of the ATF1 gene in clear cell melanoma tumorigenesis,
      similar to clear cell sarcoma with classical t(12;22) translocation.

PMID- 16285302
TI  - Amelanotic/Hypomelanotic melanoma--is dermatoscopy useful for diagnosis?
AB  - BACKGROUND: Amelanotic/hypomelanotic melanoma often leads to delayed clinical
      diagnosis because its clinical appearance can mimic other hypopigmented skin
      conditions. Dermatoscopy (dermoscopy, epiluminescence microscopy) is thought to
      be a helpful diagnostic tool in pigmented skin lesions, but it can be used also
      in non-pigmented skin tumors due to the recognition of vascular structures not
      visible to the naked eye. OBJECTIVE: 7 amelanotic/hypomelanotic melanomas in 6
      patients were analyzed in order to define their dermatoscopic findings using
      standard pattern analysis. METHODS: Clinical and dermoscopic images of each
      lesion were obtained using Dermaphot (Heine Optotechnik, Herrsching, Germany),
      with 10-fold magnification of the lesion and the color slides were converted to
      digital format using a Kodak Photo CD system. RESULTS: All 7
      amelanotic/hypomelanotic melanomas revealed peculiar dermatoscopic findings,
      namely, atypical vessels, dotted vessels, and a central pink to white veil. In
      addition, in 2 patients a slight brownish homogenous pigmentation at the
      periphery of the lesion was observed. In one case the correct diagnosis was done
      by an experienced dermatologist using dermatoscopy, whereas in the remaining 6
      cases the clinical diagnoses included squamous cell carcinoma, Bowen disease,
      pyogenic granuloma and basal cell carcinoma. In 2 of 6 patients
      amelanotic/hypomelanotic melanoma was associated with a previous history of
      melanoma. CONCLUSION: Amelanotic/hypomelanotic melanoma exhibits as a common
      dermatoscopic denominator atypical vessels, varying in size and shape, usually
      associated with a central pink to white veil.

PMID- 16285303
TI  - [Benign course of malignant atrophic papulosis (Kohlmeier-Degos disease): lack of
      vessel occlusion as good prognostic sign?].
AB  - Morbus Kohlmeier-Degos is a rare systemic disease characterized by pathognomonic
      cutaneous lesions with typical histology. We report the case of a 22-year-old
      woman with a benign course of this disease and discuss therapeutical options. The
      patient presented with whitish papules on neck, trunk and extremities that slowly
      developed within seven months. Examination of the skin revealed about 20 papules
      of 2-5 mm size. The lesions were partly skin-colored, partly with an erythematous
      rim and showed a central porcelain-like atrophy. Histology showed an interface
      dermatitis and a wedge-shaped mucin deposition with sclerosis of the upper
      reticular dermis. Organ manifestation was absent. The patient was started on a
      daily therapy of 300 mg acetyl salicylic acid. Over the course of 24 months
      single new lesions appeared at a reduced frequency. Apart from the malignant form
      of Morbus Kohlmeier-Degos there exists a benign course which may be successfully
      controlled with anti-platelet therapy. We speculate that the lack of vessel
      occlusion in the histology could be a hallmark of a benign form of this rare
      disease.

PMID- 16285304
TI  - [Cholesterol emboli during coumarin therapy].
AB  - A 71-year-old patient suddenly developed a painful, bizarre livid erythema on the
      right foot. Based upon the clinical and histological presentation, cholesterol
      emboli were diagnosed. These cholesterol emboli were induced by therapy with
      phenprocoumon (a coumarin derivative), which had been initiated 5 months
      previously. Arterial emboli may rarely occur during anticoagulation and have to
      be included in the differential diagnosis.

PMID- 16285305
TI  - [The use of TNF-alpha antagonists in dermatology].

PMID- 16285306
TI  - [Multiple papules and nodules and on the scrotum of a 34 year-old patient].

PMID- 16285307
TI  - [Herpes zoster and Herpes zoster pain . From the Working Group on Dermatologic
      Infectiology of the German Dermatology Society].

PMID- 16285308
TI  - [Letter discussing butcher's warts -- an occupational disease?].

PMID- 16285309
TI  - [Comment. HPV7-induced skin warts in butchers: an occupational disease?].

PMID- 16285310
TI  - [Photodynamic therapy--moving under the right light].

PMID- 16285311
TI  - [Factors influencing the microscopic appearance of melanocytic nevi].
AB  - Both clinicians and dermatopathologists must be aware of the various factors
      which can influence the histopathologic appearance of melanocytic nevi in order
      to avoid mistaken diagnoses.

PMID- 16285312
TI  - [Photodynamic therapy with methylaminooxopentanoate (Metvix) and a broad band
      light source (PhotoDyn 501): practical experiences in problem-patients with
      actinic keratoses and basal cell carcinomas].
AB  - BACKGROUND: Actinic keratoses (AK) and basal cell carcinomas (BCC) may represent
      a therapeutic challenge because of special subtypes, location, previous therapy
      or accompanying diseases. Photodynamic therapy (PDT) offers a semi-conservative
      treatment option for selected indications. PATIENTS AND METHODS: 28 outpatients
      who had been admitted as complicated dermato-oncologic cases because of AK (n =
      22) and BCC (n = 6) were treated with PDT, using methylaminooxopentanoate (MAOP,
      Methyl-Ala, Metvix) and a broad band light source (PhotoDyn 501). The treatment
      was evaluated for efficacy and subjective tolerance (local discomfort and pain).
      RESULTS: A complete remission (CR) was achieved in 11/22 AK (50%) and 4/6 BCC
      (67%) cases. All three cases of a superficial BCC subtype underwent a CR. Among
      responders, tolerance was good in 12/15 cases (80%), as compared to 4/13 cases
      (31%) in non-responders. Focusing on 16/28 patients with good tolerance (57%),
      there was a CR in 12 cases (75% rate), whereas for the 12/28 patients with
      moderate to poor tolerance a CR was achieved in only 3 cases (25% rate). In a
      subgroup of 8 patients who, partly due to secondary diseases, were taking
      systemic retinoids or immunosuppressive-cytostatic medications, a CR was achieved
      in 3/8 cases (38%) with a good tolerance in only 1/8 cases (13%). CONCLUSION:
      These observations confirm a good efficacy and tolerance of PDT in > or = 50% of
      a AK/BCC problem patient cohort. We found indications for 1) a positive
      correlation between efficacy and subjective tolerance as well as 2) the
      presumptive existence of a retinoid-dependent cutaneous PDT hyperalgesia.
      Effective pain control seems to be an essential cofactor for the success of PDT.

PMID- 16285313
TI  - [Quality of life and occupational dermatoses--development and evaluation of a
      questionnaire assessing quality of life with in patients with occupational
      dermatoses (LIOD--Life Quality Index Occupational Dermatoses)].
AB  - BACKGROUND: Quality of life (QOL) is an established parameter in dermatology; it
      is known that skin diseases can affect QOL adversely. There are no specific
      questionnaires that consider the consider the effect of occupational factors as
      triggers for work-related diseases, even though such a questionnaire could link
      QOL specifically with the work situation. PATIENTS AND METHODS: Based on a
      literature search and the analysis of existing study instruments, a questionnaire
      reflecting "Life Quality Index Occupational Dermatoses (LIOD)" was developed and
      studied in four different groups of persons (N = 228) with and without
      dermatological diseases. RESULTS: Using the "Guidelines for QOL-assessment in
      dermatological studies", a test comparing LIOD to established instruments showed
      a reliability quotient of 0.804. Cronsbach's alpha was 0.898. The logical and
      discriminate validity were tested and found to be significant. Hypotheses that
      had been devised while developing the test were confirmed. CONCLUSIONS: The
      validated LIOD questionnaire is a valuable addition to existing instruments in
      dermatology. LIOD may be used to gain data reflecting the efficacy of therapeutic
      strategies comparable to medical data.

PMID- 16285314
TI  - [Adverse reaction to the azo dye Pigment Red 170 in a tattoo].
AB  - A 30-year old white male presented with sharply demarcated pruritic lesions in a
      black and red tattoo on his wrist. The strongly infiltrated and slightly scaly
      eruptions started four months after tattoo application and were notably
      restricted to the red-colored areas. Symptoms got worse after UV exposure. Patch
      testing and photo patch testing with the used azo dye Pigment Red 170 (C.I.
      12475) was negative. Histology revealed lichenoid dermatitis without signs of a
      granulomatous reaction. The verification of allergic sensitization in
      hypersensitivity reactions to tattoos by patch testing may be difficult due to
      the poor penetration into the skin of the applied azo pigments. Intradermal
      testing may be more sensitive but bears the risk of long lasting skin reactions.

PMID- 16285315
TI  - [Systemic lupus erythematosus with atrophic blanche-like palmar lesions].
AB  - A 17 year-old female patient presented with porcelain-white scars on her palms
      which resembled malignant atrophic papulosis (Kohlmeier-Degos disease). We
      discuss the differentiation of this syndrome from the specific cutaneous
      manifestations of systemic lupus erythematodes, the pathogenetic background, and
      treatment options.

PMID- 16285316
TI  - [Mechanisms of cutaneous drug reactions].

PMID- 16285317
TI  - [Ulcerated red, livid nodule on the scrotum of a 64-year old man].

PMID- 16285318
TI  - [Evidence-based and consented guideline on allergy prevention].

PMID- 16285319
TI  - [Online bedside teaching: multimedia, interactive and case-based teaching
      scenarios in dermatology].
AB  - The MeduMobile project or Mobiler Campus Charite was started in the beginning of
      2003 to evaluate new, multimedia supported teaching and learning scenarios. The
      project focuses especially on acute and rare diseases to which students usually
      have are very limited access. During the teaching sessions the MeduOnCall team
      and the academic teacher communicate with the students who are equipped with
      individual notebooks through a wireless net. In dermatology the MeduMobile
      project focused in summer 2003 and winter 2003/2004 on bedside teaching. Despite
      some technical difficulties in the beginning the project was well received by
      teachers and students. The possibility of simultaneous online searches by
      Internet as well as the possibility to include photographs depicting the course
      of the skin disease was felt to be one of the main advantages of this project.
      Based on these positive experiences an attempt will be made to integrate the
      project further into the regular teaching of the Charite.

PMID- 16285320
TI  - [Mouse skin as a model].

PMID- 16285321
TI  - [Graft-versus-host disease: a dermatologic view of an interdisciplinary problem].
AB  - Graft-versus-host disease (GVHD) is a frequent complication following
      hematopoietic stem cell transplantation. Acute and chronic GVHD are identified
      based on the onset of clinical symptoms and signs. Whereas acute GVHD is
      relatively uniform in its appearance, chronic GVHD is characterized by a broad
      spectrum of clinical manifestations. The aim of this review is to introduce the
      reader to the pathophysiologic processes underlying GVHD, to demonstrate its
      manifestations in the skin and to review current therapeutic options.

PMID- 16285322
TI  - [Alopecia areata in animal models--new insights into pathogenesis and treatment
      of a T cell-mediated autoimmune disorder].
AB  - Alopecia areata is a common disease, but for ethical reasons it seems difficult
      to perform large-scale studies to elucidate the pathogenesis and to develop new
      therapeutic approaches in man. It is therefore helpful to develop appropriate
      animal models. The Dundee experimental bald rat (DEBR) and the C3H/HeJ mouse are
      well-established animal models for alopecia areata and can be used for the study
      of genetic aspects, pathogenesis and therapy of the disease. In C3H/HeJ mice
      alopecia areata can be experimentally induced by grafting lesional skin from an
      affected mouse to a histocompatible recipient which offers the possibility to
      study the influence of various factors on the development of the disease. Studies
      on the C3H/HeJ mouse and the DEBR have corroborated the concept that alopecia
      areata is a T-cell mediated autoimmune disease and various steps and aspects of
      the pathogenesis have been elucidated. Based on this knowledge new therapeutic
      options may be developed such as inhibition of lymphocyte-homing by an anti
      CD44v10 antibody, or inhibition of costimulation by monoclonal antibodies.
      Therapeutic studies in the C3H/HeJ mouse and the DEBR suggest that alopecia
      areata can be treated by topical tacrolimus but treatment in humans may only be
      successful after development of an improved vehicle that facilitates penetration
      of tacrolimus down to the hair bulb. Current investigations in mice are designed
      to elucidate the mechanisms how contact sensitizers act in the treatment of
      alopecia areata, and this will hopefully lead to the development of more specific
      approaches based on the beneficial effect of contact sensitizers.

PMID- 16285323
TI  - [Periocular dermatitis].
AB  - BACKGROUND: Perioral dermatitis paradoxically sometimes spares the entire
      perioral region. There may be isolated periocular involvement (periocular
      dermatitis). PATIENTS/METHODS: The records of 23 patients with only periocular
      dermatitis were reviewed with respect to the following parameters: clinical
      findings, history of atopy, topical facial treatment, prick and patch tests, CAP
      SX1, previous treatment, time to healing and relapses. 23 patients with no
      history of periocular dermatitis were matched for age and sex (case-control
      study). RESULTS: The predominant clinical finding in the affected group was
      micropapules primarily in the lateral corner of the eye and lower eyelid. The
      groups differed significantly (p < 0.05) with regard to the history of atopic
      diseases and reactive prick tests. 22 patients regularly used face-care or eye
      care products. These patients did not differ significantly from the control group
      with regard to frequency and type of product used. 6 patients had been previously
      treated with topical corticosteroids. The time to healing was 2-8 weeks (median:
      4 weeks). CONCLUSIONS: Periocular dermatitis is a variation on perioral
      dermatitis, where-by similar pathogenetic factors are observed. The elimination
      of topical corticosteroids and the gradual reduction of skin-care products
      regularly lead to clearing of the condition.

PMID- 16285324
TI  - [Health economic studies in dermatology--review of the literature, evaluation and
      practical aspects].
AB  - BACKGROUND: Health economic studies attempt to objectivity treatment results to
      place them in economic. These studies summarize both physician care and other
      medical services to allow a more rational use of limited resources and are of
      great value. METHODS: The health economic studies in the literature were analyzed
      by the conducting countries, financing, the study period and the interval until
      publication. A quantitative comparison to other specialties in medicine was
      performed. On the basis of a checklist of basic criteria, a qualitative
      assessment of the studies was performed to rate the significance. RESULTS: The
      number of studies showed a fivefold increase. A third of the dermatological
      studies (n = 71) were conducted in the United States, 23.94% in Great Britain,
      9.86% in Sweden and 35.23% in other countries. The interval until publication was
      0 to 9 years. CONCLUSIONS: The increase in the number of studies may be explained
      by the growing demand for clarification of the economical situation. Reasons for
      the significant differences between different countries might be the financing of
      the studies or the nature of the dominant health care system. Whereas American
      studies are predominantly sponsored by pharmaceutical companies, the ones in
      Great Britain and Sweden are supported by public authorities. The long delays in
      publishing may be accounted for by long review periods and by difficulties in
      transferring large amounts of data in international studies. Particularly the
      introduction of the DRG system in Germany has increased demands for cost
      effective action on the basis of well-founded and high-quality health economic
      studies.

PMID- 16285325
TI  - [Relapsing polychondritis as a rare different diagnosis of erysipelas].
AB  - A 76-year old patient with painful erythematous swelling of the right ear was
      initially treated with antibiotics under the suspected diagnosis of erysipelas.
      Her failure to respond and a history of previous laryngeal and nasal swelling
      suggested the possibility of relapsing polychondritis. High dose prednisolone
      therapy produced marked improvement. Relapsing polychondritis should be
      considered as a rare, but important differential diagnostic consideration for
      erysipelas.

PMID- 16285326
TI  - [Nonsurgical breast enlargement using a vacuum brassiere for tissue expansion].
AB  - We present a method for nonsurgical breast enlargement using a vacuum tissue
      expander and describe the first so-treated patient in Germany. The patient wore a
      brassiere-like system that applied a mild (average 20.4 mm Hg) vacuum distraction
      force to each breast for 10.6 hours/ day over a 10-week period. An increase of 5
      cm chest circumference at the nipple level from 85 cm to 90 cm was measured at
      the end of the therapy. At 3 months follow-up visit, after resorption of the
      therapy-induced edema, there was still a gain of 4 cm resulting in a 89 cm chest
      circumference as well as natural attractive breast shape. Side effects included
      the brief occurrence of irritant contact dermatitis and folliculitis during
      therapy. The supposed mechanism is analogous to other tissue expansion methods,
      where tissue growth is a response to continuous controlled mechanical forces.
      This nonsurgical and non-invasive alternative for breast enlargement appears
      effective and well-tolerated. Because the only relevant side effects involve the
      skin, dermatologists are well-suited to perform the treatment.

PMID- 16285327
TI  - [Telemedicine in dermatology 2003: a review].

PMID- 16285328
TI  - [35-year old female with livid erythmic plaques on the face, fingers and the
      thigh].

PMID- 16285329
TI  - [Therapy for pathologic scars (hypertrophic scars and keloids)].

PMID- 16285330
TI  - Changes in prevalence of and prescribing for ischaemic heart disease in Ireland
      1990-2002.
AB  - BACKGROUND: Secondary prevention therapies, such as angiotension converting
      enzyme (ACE) inhibitors, beta-blockers and statins, are known to reduce
      cardiovascular morbidity and mortality. OBJECTIVE: The aim of the study was to
      examine the prevalence of coronary heart disease (CHD) and the prescribing of
      secondary preventive therapies in the period 1990-2002. METHODS: The General
      Medical Services prescription database was used to identify the study cohort,
      those with CHD, in each year 1990-2002. CHD was defined in two ways: prescription
      of any nitrate, and co-prescription of nitrate and aspirin. In addition, co
      prescription of secondary preventive agents including statins, ACE inhibitors and
      beta blockers were examined. RESULTS: We found a significant increasing
      prevalence of CHD from 1990 to 2002 in both men and women. There was a
      significant increase (p < 0.0001) in the prescribing rate for beta blockers, ACE
      inhibitors, and for statins, buta significant decrease (p < 0.0001) for calcium
      channel blockers. CONCLUSION: These trends reflect the growing evidence base on
      the effectiveness of secondary preventive therapies, and the implementation of
      the National Cardiovascular Health Strategy.

PMID- 16285331
TI  - Efficacy of fibrinolysis in the emergency department for acute myocardial
      infarction.
AB  - BACKGROUND: Patients with an acute myocardial infarction require a rapid response
      to their symptoms and the earlier fibrinolysis is given (where indicated), the
      better the outcome. AIMS: The aim of this study is to compare 'door to needle
      times' for fibrinolysis in Acute Myocardial Infarction (AMI) in three phases of
      one year each, at Letterkenny General Hospital. METHODS: In the PREINTERVENTION
      year all fibrinolysis was performed in the Coronary Care Unit (CCU). In the
      INTERVENTION year Emergency Department (ED) fast track fibrinolysis was
      introduced and in the POST INTERVENTION year most fibrinolysis was performed on
      fast track in the ED. RESULTS: The time saved by the introduction of ED
      fibrinolysis was significant, 41 minutes on average per patient. Elderly, female
      patients were more likely to bypass ED fast track fibrinolysis and to be brought
      to CCU for fibrinolysis, with attendant delays. This has educational implications
      in relation to the variation in clinical presentation of AMI with age and sex.
      CONCLUSION: The ED fast track fibrinolysis system is recommended as an effective,
      safe, achievable and worthwhile intervention towards improving 'door to needle
      times' for fibrinolysis in AMI.

PMID- 16285332
TI  - Outcome of bone marrow transplantation in acquired and inherited aplastic anaemia
      in the Republic of Ireland.
AB  - BACKGROUND: Severe Aplastic Anaemia (SAA) and Fanconi Anaemia (FA) are rare
      haematological disorders characterised by pancytopenia and bone marrow
      hypoplasia. AIMS: We performed a retrospective study of all patients who
      underwent BMT for SAA and FA at St James's Hospital, Dublin, and at OLHSC,
      Crumlin, between 1985 and 2002. METHODS: The medical records of 63 patients, 50
      with acquired SAA and 13 with FA, were reviewed. RESULTS: The median age at the
      time of transplant was 14 years (range 3-43 years). The actuarial survival (OS)
      (n = 63) was 76% at 17 years. The transplant related mortality (TRM) was 22% (n =
      14). The most common cause of death was infection (46%). The survival was
      significantly better in patients receiving their transplant after 1995 (p =
      0.002). Outcome was superior in those receiving less than 20 red cell
      transfusions prior to transplant: OS 91% (< 20 Units) versus 62% (> or = 20
      Units). CONCLUSIONS: These national results are comparable to those of published
      international series and support the use of BMT in the treatment of SAA and FA.
      The known adverse effect of prior transfusion was confirmed.

PMID- 16285333
TI  - The incidence of postoperative venous thrombosis among patients with ulcerative
      colitis.
AB  - BACKGROUND: Patients with Ulcerative Colitis (UC) have inherent prothrombotic
      tendencies. It is unknown whether this necessitates the use of additional
      perioperative anti-thrombotic prophylaxis when such patients require major
      surgery. METHODS: The postoperative courses of 79 patients with UC undergoing 180
      major abdominal and pelvic operations were examined for clinical and radiological
      evidence of venous thrombosis. Eighteen patients with Familial Adenomatous
      Polyposis (FAP) having surgery (35 operations) of similar magnitude were also
      studied. Standard anti-thrombosis prophylaxis was utilised in all patients.
      RESULTS: Nine patients with UC were clinically suspected of developing
      postoperative venous thrombosis, but only three (3.8%) had their diagnosis
      confirmed radiologically (all had a pulmonary embolus). Therefore, the overall
      postoperative thrombosis rate, on an intention to treat basis, was 1.7% (3/180).
      No patient with FAP developed significant venous thrombosis. CONCLUSION: Standard
      perioperative antithrombotic modalities are sufficient to maintain any potential
      increase in postoperative thrombotic risk at an acceptable level in patients with
      UC undergoing operative intervention.

PMID- 16285334
TI  - Impact of the informed consent process on patients' understanding of varicose
      veins and their treatment.
AB  - AIM: It is particularly important that patients have reasonable understanding of
      the risks, benefits and nature of elective surgery. This study sought to analyse
      this level of understanding in patients undergoing varicose vein surgery METHODS:
      Eighty two patients completed a questionnaire in the vascular outpatient clinic
      and were asked to complete a telephone questionnaire following the clinic.
      RESULTS: Pain (n = 46) was the primary reason patients considered varicose vein
      surgery followed by appearance (n = 32). Most patients felt that varicose veins
      placed them at high risk of leg ulcers (n = 46) and DVT (n = 41). A high level of
      expectation that surgery would significantly affect pain and flares was recorded.
      While the outpatient visit did not materially change these misconceptions, an
      educational leaflet significantly enhanced the recall of complications (p =
      0.028) in patients who remembered receiving a leaflet. CONCLUSION: Patients
      attending varicose vein clinics have an unrealistic expectation of the benefits
      of surgery and fail to understand the benign nature of their condition. The
      outpatient process has little effect on patient-held beliefs.

PMID- 16285335
TI  - Falls in an acute hospital and their relationship to restraint use.
AB  - BACKGROUND: Patient falls are a common complication of hospitalisation. Use of
      restraints in patients who are perceived to be at risk for falling may lead to
      injury and even death. AIMS: To determine the frequency of falls and fall-related
      injuries and the contribution of restraints in a hospital population. METHODS: We
      analysed incident reports of falls for a single year from a large teaching
      hospital. Results The fall rate per 10,000 patient days was 13.2 (95%CI 11.6
      14.8). Fall rate increased dramatically with increased age. Eighty-two (30.7%)
      falls resulted in injury, of which 6 (7.3%) were serious. Injuries occurred in
      71/247 (29%) unrestrained falls and in 11/20 (55%) falls in patients who were
      restrained. Injuries were more severe in falls with restraints in place (p <
      0.0001). CONCLUSIONS: Restraint use is associated with increased severity of
      injury in hospital patients who fall.

PMID- 16285336
TI  - Guidelines for the management of hepatitis C in general practice: a semi
      qualitative interview survey of GPs' views regarding content and implementation.
AB  - BACKGROUND: Hepatitis C is a common infection among people who attend GPs for
      methadone maintenance treatment. AIM: To determine the views of GPs towards
      clinical guidelines for the management of hepatitis C among current or former
      injecting drug users in advance of their implementation. METHODS: A purposive
      sample of 14 GPs (10% of the total prescribing methadone at the time the
      guidelines were developed) was invited to review a pre-publication draft of the
      guidelines and interviewed regarding content, presentation, perceived barriers to
      implementation and suggested interventions to facilitate effective implementation
      of the guidelines. RESULTS: GPs indicated the guidelines were useful but
      suggested aspects of presentation should be clarified. Organisational issues were
      identified as the principal barriers to effective implementation, with the
      provision of additional nursing support the principal intervention suggested to
      facilitate implementation. CONCLUSIONS: Interviewing intended recipients may be
      an important step in ensuring clinical practice guidelines are effectively
      implemented.

PMID- 16285338
TI  - Attitudes to peer review as a competence assurance structure--results of a survey
      of Irish physicians.
AB  - BACKGROUND: The Medical Council in Ireland is currently implementing Competence
      Assurance Structures (CAS). Peer review has been proposed as a tool to measure
      physician competence. AIMS: To assess the attitudes of physicians working in the
      Irish healthcare system to a peer review programme of competence assurance prior
      to its implementation. METHODS: A postal survey was sent to all physicians in the
      Irish Medical Directory in November 2003. Nine questions were asked to gauge
      attitudes to peer review as a CA tool. The returned questionnaires were collated
      and data extracted based on responses. RESULTS: The response rate was 67%. The
      majority of respondents (92%) felt peer review would inform competence assurance
      in Ireland. Most physicians who were surveyed felt an on-site assessment (88%)
      every 5 years (87%) was the preferred method. Over 30% responded that there
      should be a financial incentive for completing a review, and 70% would pay to be
      assessed. The UK model of competence assurance was the model most physicians
      preferred for the Irish setting (42%). CONCLUSION: The majority of physicians
      practising in Ireland would favour a peer review system of competence assurance.
      The financial implications, and structure, of such a system would need to be
      explored prior to implementation.

PMID- 16285337
TI  - Schizophrenia in general practice: a national survey of general practitioners in
      Ireland.
AB  - BACKGROUND: Chronic schizophrenia is challenging to manage in primary care. AIMS:
      We sought to establish the views of General Practitioners about managing patients
      with chronic schizophrenia in primary care. METHODS: A cross-sectional, postal
      survey questionnaire of a randomly selected sample of 20% of GPs was carried out.
      RESULTS: Most GPs (97.2%) have at least one person with schizophrenia attending
      their practice. A substantial number of GPs (22.2%) treat cases of schizophrenia
      without specialist input following an initial referral to psychiatric services.
      Almost all (88.7%) advised patients who had experienced multiple relapses to
      remain on medication indefinitely. One third of GPs reported that they always
      experience difficulties managing patients with schizophrenia in their practice.
      Non-adherence with prescribed medication and loss to follow-up were the commonest
      impediments to treatment encountered. CONCLUSION: GPs require appropriate back up
      from specialist services to enable their management of chronic schizophrenia.

PMID- 16285339
TI  - General practice out-of-hours co-operatives in Ireland-emergency service or not?
AB  - BACKGROUND: Since 1998, Irish general practice has developed 11 out-of-hours co
      operatives, covering almost 40% of the population.The co-operatives vary in terms
      of triage mechanisms, treatment centres and domiciliary visits but no data exist
      on their role in the management of emergencies in the community. AIMS: To
      describe the role of co-operatives in the management of emergencies, both in
      quantitative and qualitative terms. METHOD: A questionnaire survey for a 12-month
      period completed by all 11 co-operatives described structures and activity
      levels. Semi-structured interviews with senior management and GPs at five
      randomly selected co-operatives explored their understanding of the role of co
      operatives. RESULTS: The incidence of emergencies is very variable (10% of all
      contacts-virtually nil) with general reliance on the skills of triage staff
      rather than use of protocols to identify emergencies. Eight of 11 co-operatives
      provide a domiciliary service with some responding to calls from ambulance
      services and Gardai for medical assistance. There are very limited liaison
      structures with ambulance services at any level. Interviews with staff reveal
      concern with a perceived role as a service dealing with 999 type calls rather
      than with emergencies encountered in the course of normal general practice work.
      CONCLUSIONS: Clarification is urgently required of the extent to which GP co
      operatives and ambulance services support each other. Examples include procedures
      for passing calls between services, mutual understanding of each others roles and
      development of common procedures.

PMID- 16285340
TI  - Elevated plasma concentrations of atrial and brain natriuretic peptide in type 1
      diabetic subjects.
AB  - BACKGROUND: The intravenous infusion of atrial (ANP) and brain (BNP) natriuretic
      peptides have been shown to increase urinary albumin excretion in type 1
      diabetes. AIMS: To measure plasma ANP and BNP concentrations in patients with
      type 1 diabetes and to examine the parameters associated with elevated plasma
      concentrations. Methods We measured plasma ANP and BNP concentrations, UAER,
      HbA1C systolic blood pressure, and left ventricular mass index. Plasma ANP and
      BNP were also measured in non-diabetic control subjects for comparison. RESULTS:
      Using multivariate regression analysis plasma ANP correlated positively with
      HbA1C (1.9 + 0.47, p = 0.0002), UAER (0.37 + 0.05, p = 0.00001), SBP (1.26 + 0.5,
      p = 0.01) and LVMI (00.46 + 0.25, p = 0.07). BNP was positively related with LVMI
      (0.95 + 0.4, p = 0.02), and UAER (0.56 + 0.08, p = 0.001). CONCLUSIONS: Plasma
      concentrations of ANP and BNP are elevated in some patients with type 1 diabetes.
      Plasma ANP concentrations are closely related to UAER and elevated plasma
      concentrations are associated with poor glycaemic control and systemic
      hypertension. Plasma BNP concentration is related to LVMI.

PMID- 16285341
TI  - The issue of anti-D: an integrated seamless approach from recognition of need to
      bedside administration.
AB  - BACKGROUND: The appropriate and timely administration of Anti-D immunoglobulin to
      Rhesus (D) negative women who have delivered Rhesus (D) positive babies is a
      vital part of obstetric care. Anti-D has an especially high profile in Ireland
      because of the tragic inadvertent transmission of Hepatitis C to Irish women in
      past decades. AUDIT: We have reviewed our policy and procedures pertaining to the
      administration of Anti-D for sensitising events during pregnancy and postnatally,
      in the Mid-Western Health Board in 1999/2000. As a result, major changes were
      made in the storage, issue, recording and administration of Anti-D. New
      procedures in the transfusion laboratory and in the maternity hospital have been
      accepted by scientists and midwives and supported by haematology and obstetric
      medical staff. The pharmacy and haematology laboratory no longer have a role in
      this programme. IMPLEMENTATION OF MULTI-DISCIPLINARY CHANGE MANAGEMENT: As a
      result of these changes, the storage, issuing and tracking of Anti-D has become
      the responsibility of the hospital blood bank. Measurement offoeto-maternal
      haemorrhage (FMH) is now the responsibility of bio medical scientists in blood
      bank, utilising both flow cytometry (increasingly recognised as the gold standard
      method) and the Kleihauer method (Kleihauer-Betke). The programme has moved from
      a doctor-administered IV Anti-D Ig, to a midwife-administered IM preparation.
      Prescription remains the responsibility of the doctor. These changes are
      facilitated by the protocol guided issue of the appropriate dose of Anti-D Ig by
      bio medical scientists to midwives. The issue of the Anti-D Ig occurs
      simultaneously with issue of results of mother and baby's serology testing and
      estimation of volume of FMH. These major changes have been guided by audit and
      needs assessment and require close liaison between medical, nursing and
      laboratory scientific staff in haematology, transfusion and obstetrics. CRITICAL
      INCIDENT AUDIT-CASE REPORT: Before new procedures became official policy, a
      critical incident audit allowed us to pilot our protocol and to revise it using
      draft new procedures. In this critical incident we describe successful management
      of a patient with a large foeto-maternal haemorrhage. This incident supported the
      need for the procedural enhancements already underway. This critical incident re
      emphasised the need for the planned systems improvements to be introduced
      quickly.

PMID- 16285342
TI  - Patient education in physiotherapy of low back pain: acute outcomes of group
      instruction.
AB  - BACKGROUND: Adults with recalcitrant mechanical low back pain of more than six
      weeks duration can encounter unacceptable waiting periods for specialised care.
      AIM: To evaluate the effectiveness of rapid treatment by means of group sessions.
      METHODS: We instituted a rapidly accessed patient education programme in
      physiotherapy for low back pain. Pain and disability were assessed before and
      after the programme. The programme included four sessions of group instruction
      for self-actuated physiotherapy There were six to 10 patients per group. RESULTS:
      In eight months, 160 patients were admitted to the programme. The average waiting
      time was 16 business days for the first appointment. Seventy-three per cent of
      the patients who attended some portion of the programme completed all sessions.
      At least 30% of the incompletions were ascribable to rapid improvement. Of
      patients completing the programme, 80% reported significant resolution of the
      pain and improvement in function. Twenty per cent reported no significant
      response, but no patients worsened during participation. Of the 20% with no
      subjective improvement, 50% were pursuing medico-legal claims. In comparison, 9%
      of those reporting a successful response were pursuing litigation. CONCLUSIONS:
      Group instruction in physiotherapy for low back pain is safe, generally
      successful, and highly acceptable to patients.

PMID- 16285343
TI  - Differences between self-referred and physician-referred hospital admissions.
AB  - AIM: Compare self- and physician-referred hospital admissions. METHODS: Analysis
      of data prospectively collected on 3,076 consecutive acute medical admissions to
      a small hospital. RESULTS: Self-referred patients were younger (50.6 vs. 63.7
      years) and more likely to be smokers and drinkers. Conversely, physician-referred
      patients were more likely to present later, be ex-smokers, ex-drinkers and have
      poor prior health. More self-referred admissions were related to parasuicide
      and/or alcohol (27% vs. 4.5%). The physical, x-ray and laboratory findings of
      both types of patient were similar. Although self-referred patients had a shorter
      length of stay (3.8 days vs. 6.0 days) and a lower death rate (1.5% vs.
      3.8%),they had higher 30-day readmission rates (14.6% vs. 8.5%). CONCLUSION: Self
      referred patients are less sick than those referred for hospital admission by a
      physician, have less psychosocial support, more alcohol-related illness and are
      nearly twice as likely to be readmitted within 30 days of discharge

PMID- 16285344
TI  - The radial artery: an alternative access site for diagnostic and interventional
      coronary procedures.
AB  - BACKGROUND: Percutaneous techniques are routinely used in the diagnosis and
      treatment of cardiovascular disease. The transfemoral route is the most
      frequently used arterial access site for performing these procedures AIM: To
      describe a technique to gain arterial access via the radial artery to perform
      diagnostic and invasive procedures. METHODS: Patient selection is key to
      establishing a successful transradial service. RESULTS: There is a significant
      vascular complication rate when using the transfemoral route. Transfemoral access
      can also be difficult in patients with peripheral vascular disease. Arterial
      access via the right radial artery represents a realistic alternative to the
      transfemoral route for performing diagnostic and therapeutic coronary procedures.
      CONCLUSIONS: The radial artery offers a safe and effective alternative access
      site for performing diagnostic and interventional coronary procedures. The need
      for alternatives to femoral artery access is critical in patients with severe
      peripheral vascular disease. The establishment and ongoing provision of radial
      artery intervention allows for a significant reduction in major vascular
      complication rates, earlier patient ambulation, increased patient comfort and the
      potential to establish day case coronary intervention.

PMID- 16285345
TI  - A case of a gastrointestinal stromal tumour presenting as acute abdomen.
AB  - BACKGROUND: Gastrointestinal stromal tumour (GIST) has many modes of
      presentation. This is the first reported GIST presenting as an acute abdomen.
      METHODS: A man presented with signs and symptoms suggestive of acute
      appendicitis. Examination under anaesthesia revealed a mass. At laparotomy a
      strangulated mass was found originating from the greater curve of the stomach.
      Subsequent histopathology confirmed this to be a gastrointestinal stromal tumour,
      probably of a benign nature. Post-operative investigations did not show any
      metastatic spread. CONCLUSIONS: GISTs arise from the gastrointestinal tract,
      omentum, and mesentery. Presentation is generally non-specific and it is rare for
      them to present acutely. Management should include staging to exclude any
      metastatic spread.

PMID- 16285346
TI  - Transient global amnesia after sexual intercourse.
AB  - BACKGROUND: Transient global amnesia presents as paroxysmal, transient loss of
      memory function and has been shown to have a number of inciting factors. AIMS: To
      report a case and its inciting factor in order to heighten awareness of the
      condition. METHODS: A 56-year-old woman who presented with TGA after sexual
      intercourse is reported. RESULTS: The episode of TGA resolved after 14 hours.
      Results of laboratory tests including MRI brain and MR angiogram and venogram
      were normal. CONCLUSION: An inciting event can often be identified for TGA and a
      targeted history should be used to help elicit such events.

PMID- 16285347
TI  - Epidural abscess causing cauda equina syndrome.
AB  - BACKGROUND: Spinal epidural abscesses are uncommon but are well documented in the
      literature as a serious causes of mortality and long-term neurological morbidity.
      AIM: We describe a case of a 57-year-old female who presented to Accident and
      Emergency with an acute exacerbation of long standing mild lower back pain with
      symptoms of cauda equina syndrome and a systemic infective process. CONCLUSION:
      The diagnosis of this condition requires a high index of suspicion. This report
      demonstrates that with adequate decompression and appropriate antimicrobial
      treatment a good outcome is achievable.

PMID- 16285349
TI  - Macroglossia and carpal tunnel syndrome associated with multiple myeloma: a case
      report.
AB  - BACKGROUND: Macroglossia is an unusual symptom in primary care. It may be an
      indicator of an underlying plasma cell dyscrasia or multiple myeloma in the
      elderly. AIM: To describe such a case of multiple myeloma. RESULTS: A 69-year-old
      man,with a recent history of bilateral carpal tunnel repair, presented to his GP
      with progressive macroglossia. This was eventually diagnosed as being due to
      amyloidosis, secondary to multiple myeloma. CONCLUSION: Physicians should be
      aware of the association between macroglossia, carpal tunnel syndrome and
      multiple myeloma in this age group.

PMID- 16285348
TI  - Gianotti-Crosti syndrome associated with HBV infection in an adult.
AB  - BACKGROUND: Gianotti-Crosti Syndrome (GCS) is a characteristic cutaneous eruption
      following a viral infection. Incidence peaks in early childhood and the syndrome
      rarely occurs in adulthood. Hepatitis associated with GCS is usually anicteric
      and acute form. AIM: To report an adult with GCS associated with HBV infection
      and presenting icteric progress. METHODS: The clinical features of the GCS case
      associated with HBV infection were evaluated. RESULT: The cutaneous lesions
      disappeared completely on the 61st day and clearance for HBsAg was also observed.
      CONCLUSION: GCS may be seen in adults and may be associated with icteric HBV
      infection.

PMID- 16285350
TI  - CT guided radiofrequency ablation of intra-articular osteoid osteoma of the hip.
AB  - BACKGROUND: Osteoid osteoma is a painful benign bone tumour. Previously the
      standard therapy was surgical excision. Image guided radiofrequency ablation can
      be clinically applied to ablate the tumour in a minimally invasive manner. AIMS:
      We present a case of an 18-year-old boy who presented with features of chronic
      left hip arthropathy secondary to intra-articular osteoid osteoma, subsequently
      successfully treated by percutaneous CT guided radiofrequency ablation. RESULTS:
      The CT guided radiofrequency ablation was technically successful as a day case
      procedure without complication. The patient returned to normal function within
      one week. No recurrence occurred in the three-year follow-up period. CONCLUSION:
      Radiofrequency ablation is a safe, minimally invasive and effective technique for
      treatment of osteoid osteoma.

PMID- 16285351
TI  - Coincidental malignancy and abdominal aortic aneurysm: a clinical conundrum.

PMID- 16285352
TI  - Surgical treatment of pulmonary embolism.

PMID- 16285353
TI  - Tigecyclin--the first glycylcycline to undergo clinical development: an overview
      of in vitro activity compared to tetracycline.
AB  - Tetracycline antimicrobials are characterised by a broad-spectrum of
      antibacterial activity which includes Gram-positive, most Gram-negative,
      anaerobic and "atypical" (Legionella pneumophila, Chlamydophila pneumoniae and
      Mycoplasma pneumoniae) species. However, the original clinical utility of the
      tetracyclines has been compromised as a result of increasing resistance to them
      among previously susceptible, common pathogens. Research into structure-activity
      relationships among various tetracycline derivatives resulted in discovery of the
      9-t- butylglycylamido tetracyclines, now known as the glycylcyclines, which are
      not affected by either specific efflux pump or ribosomal protection mechanisms of
      resistance. Tigecycline, 9-t-butylglycylamido-minocycline, is the first in the
      glycylcycline class to undergo clinical development. This review of published in
      vitro data clearly demonstrates the potent activity of tigecycline against a wide
      range of common hospital and community bacterial pathogens including those having
      acquired mechanisms of resistance to older congeners (tetracycline, minocycline
      and doxycycline). Its activity against multiply-resistant Staphylococcus spp,
      including glycopeptide-intermediate strains (GISA), Streptococcus pneumoniae,
      Enterococcus spp. (including vancomycin-resistant strains) and some extended
      spectrum, beta-lactamase producing isolates of species of the Enterobacteriaceae,
      is particularly noteworthy.

PMID- 16285354
TI  - Pharmacokinetics, pharmacodynamics, safety and tolerability of tigecycline.
AB  - The pharmacokinetics and pharmacodynamics of tigecycline have been extensively
      studied in laboratory models and healthy volunteers. Tigecycline is available as
      a parenteral agent, exhibits linear pharmacokinetics, has a long terminal half
      life, is extensively distributed into the tissues and attains steady-state levels
      in serum by day 7. The pharmacokinetics of tigecycline appear unaffected by age,
      renal disease and food. Clinical trials have shown that tigecycline (50 mg i.v.
      q12h) in adults is safe and generally well tolerated for up to 11.5 days. Drug
      related adverse events, which are typically mild to moderate in intensity and of
      limited duration, mainly include nausea and vomiting. Tolerability of tigecycline
      in fasting subjects is improved by the use of antiemetics. C. difficile-related
      complications with tigecycline are uncommon. In the majority of patients,
      tigecycline has minimal adverse effects on blood chemistry or haematology.

PMID- 16285355
TI  - Efficacy of tigecycline in complicated skin and skin structure infections and
      complicated intra-abdominal infections.
AB  - Treatment of complicated skin and skin structure infection (cSSSI) and
      complicated intra-abdominal infection (cIAI) currently present a therapeutic
      challenge because many of the pathogens involved are becoming resistant to
      standard antimicrobial therapy. Tigecycline is a novel glycylcycline that
      exhibits expanded broad-spectrum antibacterial activity against certain resistant
      pathogens. Results from randomised Phase III studies comparing the clinical and
      microbiological efficacy of tigecycline with combination antimicrobial therapy
      for the treatment of cSSSI and cIAI are encouraging. Tigecycline has the
      potential to be used as monotherapy for the treatment of cSSSI and cIAI.

PMID- 16285356
TI  - [Three patients with autoimmune hepatitis: the importance of early diagnosis and
      remission].
AB  - A 70-year-old woman presented with impaired memory and depressive symptoms and
      two women aged 53 and 30 years, respectively, presented with general malaise and
      fatigue. All were diagnosed with and treated for autoimmune hepatitis (AIH). The
      first patient developed a relapse during treatment withdrawal; she recovered and
      maintained remission after the initial dose of medication had been restarted and
      the medication was tapered more gradually. The second patient had an incomplete
      remission and later developed liver failure; she was eligible for a liver
      transplant. The third woman became pregnant during treatment and developed a
      relapse after delivery; remission was induced and maintained after the
      immunosuppression was temporally increased. AIH is a chronic progressive liver
      disease characterised by abnormal serum levels of liver enzymes,
      hypergammaglobulinaemia, auto-antibodies against cell nuclei (ANA), smooth muscle
      (SMA), or liver and kidney microsomes (LKM), interface hepatitis and the absence
      of other chronic liver disease. Early diagnosis is essential because therapy can
      markedly improve prognosis. However, there is no specific diagnostic test for
      AIH. It is important to induce and maintain remission with immunosuppressive
      therapy.

PMID- 16285357
TI  - [Effective chemotherapy for hormone-refractory prostate cancer: docetaxel
      prednisone].
AB  - During the past decades, the results of the treatment of patients with hormone
      refractory prostate cancer (HRPC) have been disappointing. The use of
      mitoxantrone plus low-dose prednisone has resulted in pain relief in some
      patients, but there was no impact on survival. Recently, two randomised studies
      have been published that show that docetaxel-containing chemotherapy, as compared
      to mitoxantrone, gave better pain relief, more improvement in the quality of life
      and even prolonged survival. Current best practice for the treatment of HRPC
      patients now therefore consists of a course of chemotherapy with docetaxel every
      three weeks, combined with prednisone.

PMID- 16285358
TI  - [Treatment of phimosis without circumcision and reconstruction of the prepuce
      following circumcision].
AB  - Phimosis of the prepuce can be treated without performing a circumcision. The
      most common and most effective treatment option is the local application
      ofcorticosteroid ointment. Should this be insufficiently effective, then the
      constricted ring can be interrupted with two Z-plasties, which is sufficient to
      expose the glans penis painlessly. No skin is removed. The intervention may be
      performed under regional anaesthesia on an outpatient basis. In cases where
      reconstruction of the prepuce is indicated, this can be accomplished with a
      distally inverted flap of penile shaft skin combined with the application of free
      skin grafts.

PMID- 16285359
TI  - [The foreskin and squamous-cell carcinoma of the penis].
AB  - The incidence of penile cancer is low in men who have been circumcised at
      infancy. It is unknown whether a causative relationship exists between
      circumcision and the substantially reduced incidence of penile cancer. A normal
      foreskin has no known aetiological role in the development of penile cancer. A
      narrow, non-retractable foreskin predisposes the patient to infection and
      contributes to the development of penile cancer, together with the known risk
      factors of smoking and human papillomavirus infection. Circumcision represents a
      complex of social and behavioural factors. Analyses have not taken all of these
      factors into consideration. It is unlikely that circumcision itself protects
      against the development of penile cancer.

PMID- 16285360
TI  - [Diagnosis image (251). A man with a tongue ulcer].
AB  - A 23-year-old man presented with a left-sided tongue ulcer caused by a squamous
      cell carcinoma.

PMID- 16285361
TI  - [Prevalence and characteristics of haemangiomas in young children].
AB  - OBJECTIVE: To obtain current data on the prevalence and characteristics of
      haemangiomas within a population-based group of children. DESIGN: Cross-sectional
      study. METHOD: During March-May 2002, all children aged 0-16 months who presented
      for regular check-ups at child health centres in the Tilburg area, The
      Netherlands, were examined by physicians for the presence of haemangiomas. The
      characteristics of the children with a haemangioma were recorded and parents were
      asked for more specific information. RESULTS: Of the 2204 children included, 219
      (10) had 256 haemangiomas. The girl-boy ratio was 19:1 The haemangioma was
      already present at birth in 24% of children. Of the 256 haemangiomas, 15% were
      located subcutaneously, 33% were located in the head-neck area and 37% on the
      body. Of the 84 haemangiomas in the head-neck area, 75% were located on the scalp
      and forehead. Of the 219 children with a haemangioma, 7% and 6% visited a general
      practitioner or specialist regarding the haemangioma, respectively. They were
      consulted particularly when the haemangioma was present at birth, located
      subcutaneously, located in the head-neck area, and when multiple haemangiomas
      were present.

PMID- 16285362
TI  - [Resistant microorganisms in patients transferred from foreign hospitals].
AB  - OBJECTIVE: To determine the prevalence of carriers of methicillin-resistant
      Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and
      gentamicin-resistant Gram-negative bacilli (GGNB) in patients repatriated from
      foreign hospitals to The Netherlands. DESIGN: Determination of prevalence.
      METHOD: In the period May 1998-August 2001, 1167 patients were repatriated. Swab
      specimens, demographic data and clinical data were obtained during the transfer.
      RESULTS: The prevalence of carriers of resistant microorganisms was 18.2%. MRSA
      was carried by 2.7% of the total repatriated group and by 4.7% of patients
      transferred to a Dutch hospital. Risk factors were antimicrobial treatment (odds
      ratio (OR): 3.4; 95% CI: 1.2-9.7), length of stay in a foreign hospital > or = 14
      days (OR: 5.4; 95% CI: 2.3-12) and artificial ventilation (OR: 8.5; 95% CI: 1.8
      41). VRE and GGNB were isolated from 2.7% and 14.1% of patients, respectively.
      Transfer from Asia or southern, south-eastern and eastern Europe were risk
      factors for carrying GGNB. CONCLUSION: Carriership of resistant microorganisms
      was high among repatriated patients. The highest risk of GGNB was more closely
      associated with the country from which the patient was transferred than the
      antimicrobial treatment received in the foreign hospital.

PMID- 16285363
TI  - [Less mutilating treatment of penile carcinoma].
AB  - Four patients with penile carcinoma are described. A 60-year-old man with a T1
      tumour underwent penis-conserving laser treatment. Two men, aged 52 and 65 years
      old, with T2-tumors and clinically node-negative groins underwent penile
      amputation. Sentinel-node biopsy (SNB) revealed no metastases in the 52-year-old
      patient. High-resolution ultrasound-guided fine-needle aspiration cytology
      revealed bilateral metastases in the other patient, who underwent bilateral
      inguinal lymphadenectomy. In the fourth patient, a 73-year-old man with a T3
      tumor, a pathological lymph node was palpated in one groin. Inguinal
      lymphadenectomy revealed 3 positive nodes and an additional pelvic
      lymphadenectomy was performed. SNB on the other side was positive and inguinal
      lymphadenectomy followed. No additional positive nodes were found in the
      dissection specimen. All patients were alive without evidence of disease 4, 3, 3
      and 4 years later, respectively. New developments in the management of penile
      cancer such as laser treatment, high-resolution ultrasonography and SNB result in
      a more tailored approach with less morbidity without reducing survival rates.

PMID- 16285364
TI  - [Infestation with the tapeworm Diphyllobothrium latum after eating raw fish].
AB  - A 31-year-old man with no relevant medical history encountered a white, ribbon
      shaped object, 15 cm long and approximately 1 cm wide, in his faeces. It turned
      out to be Diphyllobothrium latum, a tapeworm that has fish as the intermediate
      host. The patient had eaten raw fish and shellfish during a holiday in Brazil 5
      months before. He recovered after a single dose of praziquantel.

PMID- 16285365
TI  - [Improving the health of scientific research in the Netherlands].

PMID- 16285366
TI  - [A man from Somalia with a painful thyroid: thyroiditis tuberculosa].

PMID- 16285367
TI  - [Diagnostic image (241). A woman with malaise, periodic fever and extreme
      fatigue].

PMID- 16285368
TI  - [Atenolol or metoprolol as beta-blocker in the treatment of hypertension].

PMID- 16285369
TI  - Open Set face recognition using transduction.
AB  - This paper motivates and describes a novel realization of transductive inference
      that can address the Open Set face recognition task. Open Set operates under the
      assumption that not all the test probes have mates in the gallery. It either
      detects the presence of some biometric signature within the gallery and finds its
      identity or rejects it, i.e., it provides for the "none of the above" answer. The
      main contribution of the paper is Open Set TCM-kNN (Transduction Confidence
      Machine-k Nearest Neighbors), which is suitable for multiclass authentication
      operational scenarios that have to include a rejection option for classes never
      enrolled in the gallery. Open Set TCM-kNN, driven by the relation between
      transduction and Kolmogorov complexity, provides a local estimation of the
      likelihood ratio needed for detection tasks. We provide extensive experimental
      data to show the feasibility, robustness, and comparative advantages of Open Set
      TCM-kNN on Open Set identification and watch list (surveillance) tasks using
      challenging FERET data. Last, we analyze the error structure driven by the fact
      that most of the errors in identification are due to a relatively small number of
      face patterns. Open Set TCM-kNN is shown to be suitable for PSEI (pattern
      specific error inhomogeneities) error analysis in order to identify difficult to
      recognize faces. PSEI analysis improves biometric performance by removing a small
      number of those difficult to recognize faces responsible for much of the original
      error in performance and/or by using data fusion.

PMID- 16285370
TI  - A biometric identification system based on eigenpalm and eigenfinger features.
AB  - This paper presents a multimodal biometric identification system based on the
      features of the human hand. We describe a new biometric approach to personal
      identification using eigenfinger and eigenpalm features, with fusion applied at
      the matching-score level. The identification process can be divided into the
      following phases: capturing the image; preprocessing; extracting and normalizing
      the palm and strip-like finger subimages; extracting the eigenpalm and
      eigenfinger features based on the K-L transform; matching and fusion; and,
      finally, a decision based on the (k, l)-NN classifier and thresholding. The
      system was tested on a database of 237 people (1,820 hand images). The
      experimental results showed the effectiveness of the system in terms of the
      recognition rate (100 percent), the equal error rate (EER = 0.58 percent), and
      the total error rate (TER = 0.72 percent).

PMID- 16285371
TI  - Scalable model-based clustering for large databases based on data summarization.
AB  - The scalability problem in data mining involves the development of methods for
      handling large databases with limited computational resources such as memory and
      computation time. In this paper, two scalable clustering algorithms, bEMADS and
      gEMADS, are presented based on the Gaussian mixture model. Both summarize data
      into subclusters and then generate Gaussian mixtures from their data summaries.
      Their core algorithm, EMADS, is defined on data summaries and approximates the
      aggregate behavior of each subcluster of data under the Gaussian mixture model.
      EMADS is provably convergent. Experimental results substantiate that both
      algorithms can run several orders of magnitude faster than expectation
      maximization with little loss of accuracy.

PMID- 16285372
TI  - Texture for script identification.
AB  - The problem of determining the script and language of a document image has a
      number of important applications in the field of document analysis, such as
      indexing and sorting of large collections of such images, or as a precursor to
      optical character recognition (OCR). In this paper, we investigate the use of
      texture as a tool for determining the script of a document image, based on the
      observation that text has a distinct visual texture. An experimental evaluation
      of a number of commonly used texture features is conducted on a newly created
      script database, providing a qualitative measure of which features are most
      appropriate for this task. Strategies for improving classification results in
      situations with limited training data and multiple font types are also proposed.

PMID- 16285373
TI  - Estimating the pen trajectories of static signatures using hidden Markov models.
AB  - Static signatures originate as handwritten images on documents and by definition
      do not contain any dynamic information. This lack of information makes static
      signature verification systems significantly less reliable than their dynamic
      counterparts. This study involves extracting dynamic information from static
      images, specifically the pen trajectory while the signature was created. We
      assume that a dynamic version of the static image is available (typically
      obtained during an earlier registration process). We then derive a hidden Markov
      model from the static image and match it to the dynamic version of the image.
      This match results in the estimated pen trajectory of the static image.

PMID- 16285374
TI  - Variational maximum A posteriori by annealed mean field analysis.
AB  - This paper proposes a novel probabilistic variational method with deterministic
      annealing for the maximum a posteriori (MAP) estimation of complex stochastic
      systems. Since the MAP estimation involves global optimization, in general, it is
      very difficult to achieve. Therefore, most probabilistic inference algorithms are
      only able to achieve either the exact or the approximate posterior distributions.
      Our method constrains the mean field variational distribution to be multivariate
      Gaussian. Then, a deterministic annealing scheme is nicely incorporated into the
      mean field fix-point iterations to obtain the optimal MAP estimate. This is based
      on the observation that when the covariance of the variational Gaussian
      distribution approaches to zero, the infimum point of the Kullback-Leibler (KL)
      divergence between the variational Gaussian and the real posterior will be the
      same as the supreme point of the real posterior. Although global optimality may
      not be guaranteed, our extensive synthetic and real experiments demonstrate the
      effectiveness and efficiency of the proposed method.

PMID- 16285375
TI  - Dynamic Trees for unsupervised segmentation and matching of image regions.
AB  - We present a probabilistic framework--namely, multiscale generative models known
      as Dynamic Trees (DT)--for unsupervised image segmentation and subsequent
      matching of segmented regions in a given set of images. Beyond these novel
      applications of DTs, we propose important additions for this modeling paradigm.
      First, we introduce a novel DT architecture, where multilayered observable data
      are incorporated at all scales of the model. Second, we derive a novel
      probabilistic inference algorithm for DTs--Structured Variational Approximation
      (SVA)--which explicitly accounts for the statistical dependence of node positions
      and model structure in the approximate posterior distribution, thereby relaxing
      poorly justified independence assumptions in previous work. Finally, we propose a
      similarity measure for matching dynamic-tree models, representing segmented image
      regions, across images. Our results for several data sets show that DTs are
      capable of capturing important component-subcomponent relationships among objects
      and their parts, and that DTs perform well in segmenting images into plausible
      pixel clusters. We demonstrate the significantly improved properties of the SVA
      algorithm--both in terms of substantially faster convergence rates and larger
      approximate posteriors for the inferred models--when compared with competing
      inference algorithms. Furthermore, results on unsupervised object recognition
      demonstrate the viability of the proposed similarity measure for matching dynamic
      structure statistical models.

PMID- 16285376
TI  - Bayesian modeling of dynamic scenes for object detection.
AB  - Accurate detection of moving objects is an important precursor to stable tracking
      or recognition. In this paper, we present an object detection scheme that has
      three innovations over existing approaches. First, the model of the intensities
      of image pixels as independent random variables is challenged and it is asserted
      that useful correlation exists in intensities of spatially proximal pixels. This
      correlation is exploited to sustain high levels of detection accuracy in the
      presence of dynamic backgrounds. By using a nonparametric density estimation
      method over a joint domain-range representation of image pixels, multimodal
      spatial uncertainties and complex dependencies between the domain (location) and
      range (color) are directly modeled. We propose a model of the background as a
      single probability density. Second, temporal persistence is proposed as a
      detection criterion. Unlike previous approaches to object detection which detect
      objects by building adaptive models of the background, the foreground is modeled
      to augment the detection of objects (without explicit tracking) since objects
      detected in the preceding frame contain substantial evidence for detection in the
      current frame. Finally, the background and foreground models are used
      competitively in a MAP-MRF decision framework, stressing spatial context as a
      condition of detecting interesting objects and the posterior function is
      maximized efficiently by finding the minimum cut of a capacitated graph.
      Experimental validation of the proposed method is performed and presented on a
      diverse set of dynamic scenes.

PMID- 16285377
TI  - Robustness of shape descriptors to incomplete contour representations.
AB  - With inspiration from psychophysical researches of the human visual system, we
      propose a novel aspect and a method for performance evaluation of contour-based
      shape recognition algorithms regarding their robustness to incompleteness of
      contours. We use complete contour representations of objects as a reference
      (training) set. Incomplete contour representations of the same objects are used
      as a test set. The performance of an algorithm is reported using the recognition
      rate as a function of the percentage of contour retained. We call this evaluation
      procedure the ICR test. We consider three types of contour incompleteness, viz.
      segment-wise contour deletion, occlusion, and random pixel depletion. As an
      illustration, the robustness of two shape recognition algorithms to contour
      incompleteness is evaluated. These algorithms use a shape context and a distance
      multiset as local shape descriptors. Qualitatively, both algorithms mimic human
      visual perception in the sense that recognition performance monotonously
      increases with the degree of completeness and that they perform best in the case
      of random depletion and worst in the case of occluded contours. The distance
      multiset method performs better than the shape context method in this test
      framework.

PMID- 16285378
TI  - MCMC-based particle filtering for tracking a variable number of interacting
      targets.
AB  - We describe a particle filter that effectively deals with interacting targets-
      targets that are influenced by the proximity and/or behavior of other targets.
      The particle filter includes a Markov random field (MRF) motion prior that helps
      maintain the identity of targets throughout an interaction, significantly
      reducing tracker failures. We show that this MRF prior can be easily implemented
      by including an additional interaction factor in the importance weights of the
      particle filter. However, the computational requirements of the resulting
      multitarget filter render it unusable for large numbers of targets. Consequently,
      we replace the traditional importance sampling step in the particle filter with a
      novel Markov chain Monte Carlo (MCMC) sampling step to obtain a more efficient
      MCMC-based multitarget filter. We also show how to extend this MCMC-based filter
      to address a variable number of interacting targets. Finally, we present both
      qualitative and quantitative experimental results, demonstrating that the
      resulting particle filters deal efficiently and effectively with complicated
      target interactions.

PMID- 16285379
TI  - A model (in)validation approach to gait classification.
AB  - This paper addresses the problem of human gait classification from a robust model
      (in)validation perspective. The main idea is to associate to each class of gaits
      a nominal model, subject to bounded uncertainty and measurement noise. In this
      context, the problem of recognizing an activity from a sequence of frames can be
      formulated as the problem of determining whether this sequence could have been
      generated by a given (model, uncertainty, and noise) triple. By exploiting
      interpolation theory, this problem can be recast into a nonconvex optimization.
      In order to efficiently solve it, we propose two convex relaxations, one
      deterministic and one stochastic. As we illustrate experimentally, these
      relaxations achieve over 83 percent and 86 percent success rates, respectively,
      even in the face of noisy data.

PMID- 16285380
TI  - Using line segments as structuring elements for sampling-invariant measurements.
AB  - When performing measurements in digitized images, the pixel pitch does not
      necessarily limit the attainable accuracy. Proper sampling of a band-limited
      continuous-domain image preserves all information present in the image prior to
      digitization. It is therefore (theoretically) possible to obtain measurements
      from the digitized image that are identical to measurements made in the
      continuous domain. Such measurements are sampling invariant, since they are
      independent of the chosen sampling grid. It is impossible to attain strict
      sampling invariance for filters in mathematical morphology due to their
      nonlinearity, but it is possible to approximate sampling invariance with
      arbitrary accuracy at the expense of additional computational cost. In this
      paper, we study morphological filters with line segments as structuring elements.
      We present a comparison of three known and three new methods to implement these
      filters. The method that yields a good compromise between accuracy and
      computational cost employs a (subpixel) skew to the image, followed by filtering
      along the grid axes using a discrete line segment, followed by an inverse skew.
      The staircase approximations to line segments under random orientations can be
      modeled by skewing a horizontal or vertical line segment. Rather than skewing the
      binary line segment we skew the image data, which substantially reduces
      quantization error. We proceed to determine the optimal number of orientations to
      use when measuring the length of line segments with unknown orientation.

PMID- 16285381
TI  - Efficient shape matching using shape contexts.
AB  - We demonstrate that shape contexts can be used to quickly prune a search for
      similar shapes. We present two algorithms for rapid shape retrieval:
      representative shape contexts, performing comparisons based on a small number of
      shape contexts, and shapemes, using vector quantization in the space of shape
      contexts to obtain prototypical shape pieces.

PMID- 16285382
TI  - Coupled parametric active contours.
AB  - We propose an extension of parametric active contours designed to track
      nonoccluding objects transiently touching each other, a task where both
      parametric and single level set-based methods usually fail. Our technique
      minimizes a cost functional that depends on all contours simultaneously and
      includes a penalty for contour overlaps. This scheme allows us to take advantage
      of known constraints on object topology, namely, that objects cannot merge. The
      coupled contours preserve the identity of previously isolated objects during and
      after a contact event, thus allowing segmentation and tracking to proceed as
      desired.

PMID- 16285383
TI  - A Gaussian mixture model based classification scheme for myoelectric control of
      powered upper limb prostheses.
AB  - This paper introduces and evaluates the use of Gaussian mixture models (GMMs) for
      multiple limb motion classification using continuous myoelectric signals. The
      focus of this work is to optimize the configuration of this classification
      scheme. To that end, a complete experimental evaluation of this system is
      conducted on a 12 subject database. The experiments examine the GMMs algorithmic
      issues including the model order selection and variance limiting, the
      segmentation of the data, and various feature sets including time-domain features
      and autoregressive features. The benefits of postprocessing the results using a
      majority vote rule are demonstrated. The performance of the GMM is compared to
      three commonly used classifiers: a linear discriminant analysis, a linear
      perceptron network, and a multilayer perceptron neural network. The GMM-based
      limb motion classification system demonstrates exceptional classification
      accuracy and results in a robust method of motion classification with low
      computational load.

PMID- 16285384
TI  - Acoustical signal properties for cardiac/respiratory activity and apneas.
AB  - Traditionally, auscultation is applied to the diagnosis of either respiratory
      disturbances by respiratory sounds or cardiac disturbances by cardiac sounds. In
      addition, for sleep apnea syndrome diagnosis, snoring sounds are also monitored.
      The present study was aimed at synchronous detection of all three sound
      components (cardiac, respiratory, and snoring) from a single spot. The sounds
      were analyzed with respect to the cardiorespiratory activity, and to the
      detection and classification of apneas. Sound signals from 30 subjects including
      10 apnea patients were detected by means of a microphone connected to a
      chestpiece which was applied to the heart region. The complex nature of the
      signal was investigated using time, spectral, and statistical approaches, in
      connection with self-defined time-based and event-based characteristics. The
      results show that the obstruction is accompanied by an increase of statistically
      relevant spectral components in the range of 300 to 2000 Hz, however, not within
      the range up to 300 Hz. Signal properties are discussed with respect to different
      breathing types, as well as to the presence and the type of apneas. Principal
      component analysis of the event-based characteristics shows significant
      properties of the sound signal with respect to different types of apneas and
      different patient groups, respectively. The analysis reflects apneas with an
      obstructive segment and those with a central segment. In addition, aiming for an
      optimum detection of all three sound components, alternative regions on the
      thorax and on the neck were investigated on two subjects. The results suggest
      that the right thorax region in the seventh intercostal space and the neck are
      optimal regions. It is concluded that for patient assessment, extensive acoustic
      analysis offers a reduction in the number of required sensor components,
      especially with respect to compact home monitoring of apneas.

PMID- 16285385
TI  - Venous catheter based mapping of ectopic epicardial activation: training data set
      selection for statistical estimation.
AB  - A source of error in most of the existing catheter cardiac mapping approaches is
      that they are not capable of acquiring epicardial potentials even though
      arrhythmic substrates involving epicardial and subepicardial layers account for
      about 15% of the ventricular tachycardias. In this subgroup of patients, mapping
      techniques that are limited to the endocardium result in localization errors and
      failure in subsequent ablation procedures. In addition, catheter-based
      electrophysiological studies of the epicardium are limited to regions near the
      coronary vessels or require transthoracic access. We have developed a statistical
      approach by which to estimate high-resolution maps of epicardial activation from
      very low-resolution multi-electrode venous catheter measurements. A training set
      of previously recorded maps is necessary for this technique so that composition
      of the database becomes an important determinant of accuracy. The specific
      hypothesis of the study was that estimation accuracy would be best when the
      training data set matches that of the test beat(s), whereby the matching was
      according to the site of initiation of the beats. This hypothesis suggests
      approaches to optimized selection of the training set, three of which we have
      developed and evaluated. One of these methods, the high-CC refinement method, was
      able to estimate the earliest activation site of left ventricularly paced maps
      within an average of 4.67 mm of the true site; in 89% of the cases (a total of
      231 cases) the error was smaller than 10 mm. In another method, MHC-Spatial
      activation, right ventricularly paced maps (239 maps) were estimated with an
      error of 7.15 mm. The average correlation coefficient between the original and
      the estimated maps was also very high (0.97), which shows the ability of the
      training data set refinement methods to estimate the epicardial activation
      sequence. The results of these tests support the hypothesis and, moreover,
      suggest that such an approach is feasible for providing accurate reconstruction
      of complete epicardial activation-time maps in a clinical setting.

PMID- 16285386
TI  - Optimized symbolic dynamics approach for the analysis of the respiratory pattern.
AB  - Traditional time domain techniques of data analysis are often not sufficient to
      characterize the complex dynamics of respiration. In this paper, the respiratory
      pattern variability is analyzed using symbolic dynamics. A group of 20 patients
      on weaning trials from mechanical ventilation are studied at two different
      pressure support ventilation levels, in order to obtain respiratory volume
      signals with different variability. Time series of inspiratory time, expiratory
      time, breathing duration, fractional inspiratory time, tidal volume and mean
      inspiratory flow are analyzed. Two different symbol alphabets, with three and
      four symbols, are considered to characterize the respiratory pattern variability.
      Assessment of the method is made using the 40 respiratory volume signals
      classified using clinical criteria into two classes: low variability (LV) or high
      variability (HV). A discriminant analysis using single indexes from symbolic
      dynamics has been able to classify the respiratory volume signals with an out-of
      sample accuracy of 100%.

PMID- 16285387
TI  - A quantitative analysis approach for cardiac arrhythmia classification using
      higher order spectral techniques.
AB  - Ventricular tachyarrhythmias, in particular ventricular fibrillation (VF), are
      the primary arrhythmic events in the majority of patients suffering from sudden
      cardiac death. Attention has focused upon these articular rhythms as it is
      recognized that prompt therapy can lead to a successful outcome. There has been
      considerable interest in analysis of the surface electrocardiogram (ECG) in VF
      centred on attempts to understand the pathophysiological processes occurring in
      sudden cardiac death, predicting the efficacy of therapy, and guiding the use of
      alternative or adjunct therapies to improve resuscitation success rates. Atrial
      fibrillation (AF) and ventricular tachycardia (VT) are other types of
      tachyarrhythmias that constitute a medical challenge. In this paper, a high order
      spectral analysis technique is suggested for quantitative analysis and
      classification of cardiac arrhythmias. The algorithm is based upon bispectral
      analysis techniques. The bispectrum is estimated using an autoregressive model,
      and the frequency support of the bispectrum is extracted as a quantitative
      measure to classify atrial and ventricular tachyarrhythmias. Results show a
      significant difference in the parameter values for different arrhythmias.
      Moreover, the bicoherency spectrum shows different bicoherency values for normal
      and tachycardia patients. In particular, the bicoherency indicates that phase
      coupling decreases as arrhythmia kicks in. The simplicity of the classification
      parameter and the obtained specificity and sensitivity of the classification
      scheme reveal the importance of higher order spectral analysis in the
      classification of life threatening arrhythmias. Further investigations and
      modification of the classification scheme could inherently improve the results of
      this technique and predict the instant of arrhythmia change.

PMID- 16285388
TI  - The contribution of motor unit pairs to the correlation functions computed from
      surface myoelectric signals.
AB  - The contribution of motor unit action potential trains (MUAPT) of distinct motor
      units (MU) to the crosscorrelation function between myoelectric signals (MES)
      recorded at the skin surface is studied. In specific, the significance of the
      correlation between the firing activity of concurrently active MUs (which results
      in cross-terms in the overall correlation function) is compared to the
      representation obtained using the contributions of single MUs at each recording
      site (auto-terms). A model for the generation of surface MUAPs is combined with
      the generation of MU firing statistics in order to obtain surface MUAPTs. MU
      firing statistics are simulated to incorporate MU synchronization levels reported
      in the literature. Alternatively, experimental firing statistics are fed to the
      model generating the MUAPTs. The contribution of individual MU pairs to the
      global myoelectric signal correlation function is assessed. Results indicate that
      the cross-terms from different MUs decrease steadily contributing very little to
      the overall correlation for record lengths as short as 30 s. Thus, the error
      expected when computing the crosscorrelation function between two channels of MES
      as the superposition of the auto-terms contributed by single MUs (i.e., ignoring
      the cross-terms from different MUs) is shown to be very small.

PMID- 16285389
TI  - A wavelet-like filter based on neuron action potentials for analysis of human
      scalp electroencephalographs.
AB  - This paper describes the development and testing of a wavelet-like filter, named
      the SNAP, created from a neural activity simulation and used, in place of a
      wavelet, in a wavelet transform for improving EEG wavelet analysis, intended for
      brain-computer interfaces. The hypothesis is that an optimal wavelet can be
      approximated by deriving it from underlying components of the EEG. The SNAP was
      compared to standard wavelets by measuring Support Vector Machine-based EEG
      classification accuracy when using different wavelets/filters for EEG analysis.
      When classifying P300 evoked potentials, the error, as a function of the
      wavelet/filter used, ranged from 6.92% to 11.99%, almost twofold. Classification
      using the SNAP was more accurate than that with any of the six standard wavelets
      tested. Similarly, when differentiating between preparation for left- or right
      hand movements, classification using the SNAP was more accurate (10.03% error)
      than for four out of five of the standard wavelets (9.54% to 12.00% error) and
      internationally competitive (7% error) on the 2001 NIPS competition test set.
      Phenomena shown only in maps of discriminatory EEG activity may explain why the
      SNAP appears to have promise for improving EEG wavelet analysis. It represents
      the initial exploration of a potential family of EEG-specific wavelets.

PMID- 16285390
TI  - Influence of the vagus nerve on respiratory patterns during early maturation.
AB  - Nonlinear dynamical analysis was performed on the phrenic neurogram before and
      after vagotomy in order to study the influence of the vagus nerve on the
      complexity of the phrenic neurogram in piglets in three age groups: 3-7 days (n =
      7); 11-19 days (n = 6); and 29-34 days (n = 8). The phrenic neurogram, generated
      by the respiratory neural networks in the medulla, projects on the diaphragm
      muscles and initiate the respiratory movement. On the other hand, the vagus
      nerves carry the information from mechanoreceptors, located at the lower airway
      and lungs, to the medulla. The data was recorded during normal breathing (eupnea)
      before and after vagotomy while piglets were ventilated with 40% O2 in N2 and
      analyzed using the approximate entropy (ApEn) method. The mean values of the
      approximate entropy before and after vagotomy during the first 7 days of the
      postnatal age were 1.32 +/- 0.1 (standard deviation) and 1.34 +/- 0.07,
      respectively. These values before and after vagotomy during the 11-19 days age
      group were 1.15 +/- 0.09 and 1.12 +/- 0.05, respectively. For the 29-34 days age
      group, they were 1.14 +/- 0.05 before vagotomy and 1.19 +/- 0.08 after vagotomy.
      These differences in the ApEn (complexity) values of the phrenic neurogram before
      and after vagotomy are not statistically different at each age group. However,
      the mean mean approximate entropy (complexity) values between the 3-7 days age
      group and the other two groups were significantly different both before and after
      vagotomy (p < 0.05) using an analysis off variance test. These results suggest
      that the vagus nerve may not be mature during early maturation in piglets.

PMID- 16285391
TI  - Multichannel fusion models for the parametric classification of differential
      brain activity.
AB  - This paper introduces parametric multichannel fusion models to exploit the
      different but complementary brain activity information recorded from multiple
      channels in order to accurately classify differential brain activity into their
      respective categories. A parametric weighted decision fusion model and two
      parametric weighted data fusion models are introduced for the classification of
      averaged multichannel evoked potentials (EPs). The decision fusion model combines
      the independent decisions of each channel classifier into a decision fusion
      vector and a parametric classifier is designed to determine the EP class from the
      discrete decision fusion vector. The data fusion models include the weighted EP
      sum model in which the fusion vector is a linear combination of the multichannel
      EPs and the EP-concatenation model in which the fusion vector is a vector
      concatenation of the multichannel EPs. The discrete Karhunen-Loeve transform
      (DKLT) is used to select features for each channel classifier and from each data
      fusion vector. The difficulty in estimating the probability density function
      (PDF) parameters from a small number of averaged EPs is identified and the class
      conditional PDFs of the feature vectors of averaged EPs are, therefore, derived
      in terms of the PDFs of the single-trial EPs. Multivariate parametric classifiers
      are developed for each fusion strategy and the performances of the different
      strategies are compared by classifying 14-channel EPs collected from five
      subjects involved in making explicit match/mismatch comparisons between
      sequentially presented stimuli. It is shown that the performance improves by
      incorporating weights in the fusion rules and that the best performance is
      obtained using multichannel EP concatenation. It is also noted that the fusion
      strategies introduced are also applicable to other problems involving the
      classification of multicategory multivariate signals generated from multiple
      sources.

PMID- 16285392
TI  - Beat-based ECG compression using gain-shape vector quantization.
AB  - An electrocardiogram (ECG) data compression scheme is presented using the gain
      shape vector quantization. The proposed approach utilizes the fact that ECG
      signals generally show redundancy among adjacent heartbeats and adjacent samples.
      An ECG signal is QRS detected and segmented according to the detected fiducial
      points. The segmented heartbeats are vector quantized, and the residual signals
      are calculated and encoded using the AREA algorithm. The experimental results
      show that with the proposed method both visual quality and the objective quality
      are excellent even in low bit rates. An average PRD of 5.97% at 127 b/s is
      obtained for the entire 48 records in the MIT-BIH database. The proposed method
      also outperforms others for the same test dataset.

PMID- 16285393
TI  - Laguerre-model blind system identification: cardiovascular dynamics estimated
      from multiple peripheral circulatory signals.
AB  - This paper presents a method for comparing multiple circulatory waveforms
      measured at different locations to improve cardiovascular parameter estimation
      from these signals. The method identifies the distinct vascular dynamics that
      shape each waveform signal, and estimates the common cardiac flow input shared by
      them. This signal-processing algorithm uses the Laguerre function series
      expansion for modeling the hemodynamics of each arterial branch, and identifies
      unknown parameters in these models from peripheral waveforms using multichannel
      blind system identification. An effective technique for determining the Laguerre
      base pole is developed, so that the Laguerre expansion captures and quickly
      converges to the intrinsic arterial dynamics observed in the two circulatory
      signals. Furthermore, a novel deconvolution method is developed in order to
      stably invert the identified dynamic models for estimating the cardiac output
      (CO) waveform from peripheral pressure waveforms. The method is applied to
      experimental swine data. A mean error of less than 5% with the measured
      peripheral pressure waveforms has been achieved using the models and excellent
      agreement between the estimated CO waveforms and the gold standard measurements
      have been obtained.

PMID- 16285394
TI  - Control of neuromuscular blockade in the presence of sensor faults.
AB  - The problem of embedding sensor fault tolerance in feedback control of
      neuromuscular blockade is considered. For tackling interruptions of feedback
      measurements, a structure based upon Bayesian inference as well as a predictive
      filter is proposed. This algorithm is general and can be applied to different
      situations. Here, it is incorporated in an adaptive automatic system for feedback
      control of neuromuscular blockade using continuous infusion of muscle relaxants.
      A significant contribution consists in the experimental clinical testing of the
      algorithm in patients undergoing surgery.

PMID- 16285395
TI  - Harmonic decomposition in PDE-based denoising technique for magnetic resonance
      electrical impedance tomography.
AB  - Recent progress in magnetic resonance electrical impedance tomography (MREIT)
      research via simulation and biological tissue phantom studies have shown that
      conductivity images with higher spatial resolution and accuracy are achievable.
      In order to apply MREIT to human subjects, one of the important remaining
      problems to be solved is to reduce the amount of the injection current such that
      it meets the electrical safety regulations. However, by limiting the amount of
      the injection current according to the safety regulations, the measured MR data
      such as the z-component of magnetic flux density Bz in MREIT tend to have low SNR
      and get usually degraded in their accuracy due to the nonideal data acquisition
      system of an MR scanner. Furthermore, numerical differentiations of the measured
      Bz required by the conductivity image reconstruction algorithms tend to further
      deteriorate the quality and accuracy of the reconstructed conductivity images. In
      this paper, we propose a denoising technique that incorporates a harmonic
      decomposition. The harmonic decomposition is especially suitable for MREIT due to
      the physical characteristics of Bz. It effectively removes systematic and random
      noises, while preserving important key features in the MR measurements, so that
      improved conductivity images can be obtained. The simulation and experimental
      results demonstrate that the proposed denoising technique is effective for MREIT,
      producing significantly improved quality of conductivity images. The denoising
      technique will be a valuable tool in MREIT to reduce the amount of the injection
      current when it is combined with an improved MREIT pulse sequence.

PMID- 16285396
TI  - Time-varying analysis methods and models for the respiratory and cardiac system
      coupling in graded exercise.
AB  - The analysis of heart period series is a difficult task especially under graded
      exercise conditions. From all the information present in these series, we are the
      most interested in the coupling between respiratory and cardiac systems, known as
      respiratory sinus arrythmia. In this paper, we show that precise patterns
      concerning the respiratory frequency can be extracted from the heart period
      series. An evolutive model is introduced in order to achieve tracking of the main
      respiratory-related frequencies and their time-varying amplitudes. Since
      respiration acts to modulate the sinus rhythm, we relate the frequencies and
      amplitudes to this modulation by analyzing in detail its nonlinear transformation
      giving the heart period signal. This analysis is performed assuming stationary
      conditions but also in the realistic case where the mean heart period, the
      amplitude, and the frequency of the respiration are time-varying. Since this
      paper is devoted to the theoretical and complete presentation of the method used
      in a physiological study published elsewhere, the capabilities of our method will
      be illustrated in a realistic simulated case.

PMID- 16285397
TI  - Distant energy transfer for artificial human implants.
AB  - The powering of human implants via inductive coupling has been an object of
      interest for the past two decades. This paper discusses some of the issues
      concerning a distant energy link used for supplying artificial human implants,
      operating at the frequency of 13.56 MHz. A procedure for the design of an energy
      receiving coil is given for general applications. A design procedure is also
      developed, with focus on coils used for supplying human implants. The correctness
      of the analysis of this later design procedure has been verified by experimental
      results. Measurements with a human tissue simulant also show little deviation
      from the predictions.

PMID- 16285398
TI  - Evaluating tear film stability in the human eye with high-speed videokeratoscopy.
AB  - High-speed videokeratoscopy (HSV) is an emerging technology that has the
      potential to acquire information on the dynamics of corneal topography and tear
      film behavior. We show that the surface regularity and asymmetry indices, which
      are traditionally used for characterizing the stability of precorneal tear film,
      have limitations in the context of HSV because they are highly sensitive to
      natural ocular microfluctuations. To overcome this problem, we propose a new
      microfluctuation-independent surface indicator. It is based on the root-mean
      square of the error of the parametric model fit to the surface. Further, we
      develop techniques for estimating the tear film build-up and break-up times. The
      tear film build-up time estimator is based on the proposed RMS fit surface
      indicator while the tear film break-up time estimator is derived directly from a
      set of consecutive HSV digital images, without the need for estimating the
      resulting corneal surface.

PMID- 16285399
TI  - Micropower circuits for bidirectional wireless telemetry in neural recording
      applications.
AB  - State-of-the art neural recording systems require electronics allowing for
      transcutaneous, bidirectional data transfer. As these circuits will be implanted
      near the brain, they must be small and low power. We have developed micropower
      integrated circuits for recovering clock and data signals over a transcutaneous
      power link. The data recovery circuit produces a digital data signal from an ac
      power waveform that has been amplitude modulated. We have also developed an FM
      transmitter with the lowest power dissipation reported for biosignal telemetry.
      The FM transmitter consists of a low-noise biopotential amplifier and a voltage
      controlled oscillator used to transmit amplified neural signals at a frequency
      near 433 MHz. All circuits were fabricated in a standard 0.5-microm CMOS VLSI
      process. The resulting chip is powered through a wireless inductive link. The
      power consumption of the clock and data recovery circuits is measured to be 129
      microW; the power consumption of the transmitter is measured to be 465 microW
      when using an external surface mount inductor. Using a parasitic antenna less
      than 2 mm long, a received power level was measured to be -59.73 dBm at a
      distance of one meter.

PMID- 16285400
TI  - Impedance characterization of microarray recording electrodes in vitro.
AB  - The mechanisms underlying performance degradation of chronically implanted
      silicon microelectrode arrays in the central nervous system (CNS) remain unclear.
      Humoral and cellular components of the brain foreign body response were evaluated
      to determine whether their presence on the electrode surface results in increased
      electrical impedance. Iridium oxide microelectrode recording arrays were
      electrically characterized in saline, culture media with 10% fetal bovine serum,
      and coated with various CNS cell types isolated from rat brain. Electrochemical
      impedance spectroscopy and cyclic voltammetry were performed using a three
      electrode system. Potential cycling caused an immediate decrease in electrical
      impedance, which increased with time toward precycling values, with the effect of
      cycling remaining significant for several days. The addition of serum caused a
      significant increase in impedance of up to 28% relative to the saline control.
      Microelectrodes coated with various cell types known to participate in the
      foreign body response caused a 20%-80% increase in impedance immediately after
      contact that remained constant or gradually increased for several weeks. Our
      findings suggest that the attachment of molecular and cellular species following
      microelectrode implantation into brain tissue likely contribute to increases in
      impedance, but do not appear sufficient to hinder recording performance.

PMID- 16285401
TI  - Counting moles automatically from back images.
AB  - Density of moles is a strong predictor of malignant melanoma, therefore,
      enumeration of moles is often an integral part of many studies that look at
      malignant melanoma. An automatic method of segmenting and counting moles would
      help standardize studies, compared with manual counting. We have developed an
      unsupervised algorithm for segmenting and counting moles from two-dimensional
      color images of the back torso region, as part of a study to evaluate the
      effectiveness of sunscreen. The method consists of a new variant of mean shift
      filtering that forms clusters in the image and removes noise, a region growing
      procedure to select candidates, and a rule-based classifier to identify moles.
      When this algorithm was compared to an assessment by an expert dermatologist, the
      algorithm showed a sensitivity rate of 91% and diagnostic accuracy of 90% on the
      test set, for moles larger than 1.5 mm in diameter.

PMID- 16285402
TI  - Calibrated current divider network for precision current delivery during high
      voltage transthoracic defibrillation.
AB  - The design of a calibrated resistive-network current divider for precision
      current delivery during transthoracic defibrillation shocks is presented together
      with test results. The current divider presents a constant 50-ohm load to the
      defibrillator and thus maintains a constant pulse shape. Current is selected
      before the shock by setting three rheostats using a computer-generated
      calibration table. Following each shock, the data acquisition and display
      software updates the calibration table based on the measured value of
      transthoracic resistance. Over a range of 15-27 A, the root-mean-square (rms)
      error for delivered versus selected current was 0.48% for a 45-ohm resistive
      load, and 0.71% for a 100-ohm load. These test results were confirmed by animal
      experiments. Over 3 dogs, the rms error was 0.49% from 15-27 A and not greater
      than 1.5% over the entire 8-44 A range.

PMID- 16285403
TI  - Wavelet-based cascaded adaptive filter for removing baseline drift in pulse
      waveforms.
AB  - This paper presents an energy ratio-based method and a wavelet-based cascaded
      adaptive filter (CAF) for detecting and removing baseline drift from pulse
      waveforms. Experiments on 50 simulated and five hundred real pulse signals
      demonstrate that this CAF outperforms traditional filters both in removing
      baseline drift and in preserving the diagnostic information of pulse waveforms.

PMID- 16285404
TI  - [Adapting medical education to meet the physician recruitment needs of rural and
      remote regions in Canada, the US and Australia].
AB  - Australia, Canada and the United States have large land masses containing many
      sparsely populated regions. Each of these countries has experienced difficulty in
      meeting the physician recruitment needs of its rural and remote regions. This
      paper reports on a study of selected Australian, Canadian and American medical
      education programs designed to meet the health professional needs of rural and
      remote areas. The study is based on published material from the institutions
      studies, supplemented by a series of interviews with senior academic officials in
      the institutions involved. The paper focuses on a range of strategies, from
      recruitment and admissions policies, to exposure to rural clinical practice and
      modified curricula, each designed to produce medical graduates with a strong
      orientation to rural practice. The study highlights the important role played by
      special government funding targeted at rural medical education initiatives and
      discusses the challenges that such initiatives face.

PMID- 16285405
TI  - [A physician demand and supply forecast model for Nova Scotia].
AB  - RATIONALE: There is well-founded concern about the current and future
      availability of Health Human Resources (HHR). Demographic trends are magnifying
      this concern -- an ageing population will require more medical interventions at a
      time when the HHR workforce itself is ageing. The lengthy and costly training
      period for most health care workers, especially physicians, poses a real
      challenge that requires planning these activities well in advance. Hence, there
      is definite need for a good HHR forecasting model. OBJECTIVES: To present a
      physician forecasting model that projects the Full-Time Equivalent (FTE) demand
      for and supply of physicians in Nova Scotia to the year 2020 for three
      specialties: general practitioners, medical, and surgical. The model enables gap
      analysis and assessment of alternative policy options designed to close the gaps.
      METHODOLOGY: The methodology for estimating demand fo physician services involves
      three steps: (i) Establishing the FT for each physician. To this end we calculate
      the income of each physician using Physician Billings Data and then identify the
      40th and 60th percentile income levels for each of the 40 specialties. The income
      levels are then used to calculate the FTE using a formula developed at Health
      Canada; (ii) Calculating the FTE for each service by distributing the FTE of each
      physician at the service level (i.e., by patient age, sex, most responsible
      diagnosis, and hospital status group); and (iii) Using Statistics Canada's
      population projections to project future demand for three broad medical
      disciplines: general practitioners, medical specialist, and surgical specialists.
      The supply side of the model employs a stock/flow approach and exploits time
      series and other data for variables, such as emigration, international medical
      graduates (IMGs), medical school entrants, retirements, mortality, and so on,
      which in turn allow us to access a host of policy parameters. RESULTS: Under the
      status quo assumption, demand for physician services will outstrip the growth in
      supply for all three specialties. CONCLUSIONS: The model can simulate supply-side
      policy changes (e.g. more IMGs, delayed retirements) and can also reflect changes
      in demand (e.g. a cure for leukemia; different work intensities for physicians).
      The model is highly parameterized so that it can accommodate shocks that may
      influence the future requirements for physicians. Once a future requirement is
      determined, the supply model can identify the policy levers (new entrants,
      immigration, emigration, retirement) necessary to close the gap between demand
      and supply. The model is a user-friendly tool made for policy makers to formulate
      appropriate physician workforce planning.

PMID- 16285406
TI  - [Migration patterns of health professionals].
AB  - The past three decades have seen the number of international migrants double, to
      reach the unprecedented total of 175 million people in 2003. National health
      systems are often the biggest national employer, responsible for an estimated 35
      million workers worldwide. Health professionals are part of the expanding global
      labour market. Today, foreign-educated health professionals represent more than a
      quarter of the medical and nursing workforces of Australia, Canada, the United
      Kingdom and the United States. Destination countries, however, are not limited to
      industrialised nations. For example, 50 per cent of physicians in the Namibia
      public services are expatriates and South Africa continues to recruit close to
      80% of its rural physicians from other countries. International migration often
      imitates patterns of internal migration. The exodus from rural to urban areas,
      from lower to higher income urban neighbourhoods and from lower-income to higher
      income sectors contributes challenges to the universal coverage of the
      population. International migration is often blamed for the dramatic health
      professional shortages witnessed in the developing countries. A recent OECD
      study, however, concludes that many registered nurses in South Africa (far
      exceeding the number that emigrate) are either inactive or unemployed. These dire
      situations constitute a modern paradox which is for the most part ignored. Shared
      language, promises of a better quality of life and globalization all support the
      continued existence of health professionals' international migration. The ethical
      dimension o this mobility is a sensitive issue that needs to be addressed. A
      major paradigm shift, however, is required in order to lessen the need to migrate
      rather than artificially curb the flows.

PMID- 16285407
TI  - Physician workforce planning and the transition to primary health care in former
      socialist countries.
AB  - With the collapse of the Soviet Union, countries in Eastern Europe and the Newly
      Independent States inherited a physician workforce that was often too large,
      dominated by specialists, and poorly prepared for the transition to primary
      health care and the addition of the family/general practice specialty. We examine
      attempts in selected countries to plan the future physician workforce, while
      attempting to reduce the size of the workforce and train physicians to lead the
      transition to primary health care (PHC). We look the impact these efforts have
      had on the current workforce and will have on the future physician workforce.
      With few exceptions, the first move after independence was to reduce the inputs
      into the physician workforce in an attempt to reduce the size of the workforce,
      considered large by western standards, in 1990 between 350 and 400 per 100, 000
      population compared to the EU average of 299. These reductions often did not
      result from planning and ignored the lengthy physician training process, leading
      to concerns for the future supply of physicians and the conclusion that many
      other factors were influencing the number of physicians. At the same time, two
      methods were being employed to rapidly prepare physicians for PHC, retraining of
      existing physicians for the short-term and the establishment of training programs
      in the faculties of medicine to train family/general practitioners (GPs) for the
      long-term. GPs per 100,000 population remained at about 102 throughout the period
      in the original EU countries, but in the new EU countries went from 51 in 1991 to
      63 in 2002. The success of the programs was varied and often depended on the
      overall organization of the physician workforce, the status of the new family
      physician within the workforce and the commitment at the national level to the
      transition to PHC. After over a decade of independence, there is still a struggle
      to have a physician workforce with the right numbers, the right specialty mix,
      and practicing in the right locations.

PMID- 16285409
TI  - Degradation of Alyssum murale biomass in soil.
AB  - The Ni-hyperaccumulating plant Alyssum murale accumulates exceptionally high
      concentrations of nickel in its aboveground biomass. The reasons for
      hyperaccumulation remain unproven; however, it has been proposed that elemental
      alelopathy might be important. High-Ni leaves shed by the plant may create a
      "toxic zone" around the plant where germination or growth of competing plants is
      inhibited. The efficacy of this argument will partially depend upon the rate at
      which leaves degrade in soil and free metals are released, and the subsequent
      rate at which metals are bound to soil constituents. To test the degradation of
      biomass of hyperaccumulators, A. murale was grown on both high- and low-Ni soils
      to achieve high- (12.0 g Ni/kg) and low- (0.445 g Ni/kg) Ni biomass. Shredded
      leaf and stem biomass were added to a serpentine soil from Oregon that was
      originally used to grow high-Ni biomass and a low-Ni control soil from Maryland.
      Biomass Ni was readily soluble and extractable, suggesting near immediate release
      as biomass was added to soil Extractable nickel in soil amended with biomass
      declined rapidly over time due to Ni binding in soil These results suggest that
      Ni released from biomass of Ni hyperaccumulators may significantly affect their
      immediate niche only for short periods of time soon after leaf fall, but repeated
      application may create high Ni levels under and around hyperaccumulators.

PMID- 16285408
TI  - The Barcelona International Symposium (21-23 April 2005). Synthesis reports.
AB  - The Symposium was held in Barcelona, Spain, with the Institut d'Estudis de la
      Salut acting as host. It gathered 51 participants working in 34 institutions
      based in 18 countries. The main objective of the Symposium was to create an
      opportunity for assessing the past trends and forecasting the future developments
      of health workforce within the various national health systems. The Symposium was
      composed of 5 sessions devoted to presentations of the papers freely contributed
      by the participants and 5 discussion sessions devoted to the following themes :
      (i) Supply of and demand for health workforce, (ii) Future trends and forecasting
      methods ; (iii) Strategies for managing and planning health workforce ; (iv)
      Health workforce in underserved areas; (v) International migration of health
      workers. Each discussion session was conducted by a discussion leader whose the
      synthesis report is displayed here below.

PMID- 16285410
TI  - Clonal variation in survival and growth of hybrid poplar and willow in an in situ
      trial on soils heavily contaminated with petroleum hydrocarbons.
AB  - Species and hybrids between species belonging to the genera Populus (poplar) and
      Salix (willow) have been used successfully for phytoremediation of contaminated
      soils. Our objectives were to: 1) evaluate the potential for establishing
      genotypes of poplar and willow on soils heavily contaminated with petroleum
      hydrocarbons and 2) identify promising genotypes for potential use in future
      systems. We evaluated height, diameter, and volume after first year budset by
      testing 20 poplar clones and two willow clones. Unrooted cuttings, 20 cm long,
      were planted in randomized complete blocks at 0.91- x 0.91-m spacing at Gary, IN,
      USA (41.5 degrees N, 87.3 degrees W). Four commercial poplar clones (NM6, DN5,
      DN34, and DN182) were planted as 20- and 60-cm cuttings. Sixty-cm cuttings
      exhibited greater height and diameter than 20-cm cuttings; however, we recommend
      continued use and testing of different combinations of genotype and cutting
      length. We identified promising genotypes for potential use in future systems and
      we recommend allocating the majority of resources into commercial poplar clones,
      given their generalist growth performance. However, further utilization and
      selection of experimental clones is needed. Specific clones rather than genomic
      groups should be selected based on the geographic location and soil conditions of
      the site.

PMID- 16285411
TI  - Effect of coal ash on growth and metal uptake by some selected ectomycorrhizal
      fungi in vitro.
AB  - Six isolates of ectomycorrhizal fungi namely, Laccaria fraterna (EM-1083),
      Pisolithus tinctorius (EM-1081), Pisolithus tinctorius (EM-1290), Pisolithus
      tinctorius (EM-1293), Scleroderma verucosum (EM-1283), and Scleroderma cepa (EM
      1233), were grown on three variants of coal ash, namely electrostatically
      precipitated (ESP) ash, pond ash, and bottom ash moistened with Modified Melin
      Norkans (MMN) medium in vitro The colony diameter reflected the growth of the
      isolates on the coal ash. Metal accumulation in the mycelia was assayed by atomic
      absorption spectrophotometry. Six metals, namely aluminum, cadmium, chromium,
      iron, lead, and nickel, were selected on the basis of their abundance in coal ash
      and toxicity potential for the present work. Growth of vegetative mycelium on fly
      ash variants and metal accumulation data indicated that Pisolithus tinctorius (EM
      1290) was the most tolerant among the isolates tested for most of the metals.
      Since this isolate is known to be mycorrhizal with Eucalyptus, it could be used
      for the reclamation of coal ash over burdened sites.

PMID- 16285412
TI  - Influence of fertilizer levels on phytoremediation of crude oil-contaminated
      soils with the tropical pasture grass Brachiaria brizantha (hochst. ex a. rich.)
      stapf.
AB  - Determination of fertilizer levels in phytoremediation of petroleum hydrocarbons
      is a complex issue, since nutrient demands of the plant and of degrading
      microorganisms in the rhizosphere have to be considered In the present work,
      three fertilizer levels were tested in a greenhouse experiment with the aim of
      optimizing growth of the tropical pasture grass Brachiaria brizantha and enhance
      microbial degradation of heavy crude oil in soil Fertilizer was applied twice in
      a concentration of 200, 300, and 400 mg each of N, P, and K per kg soil before
      and after the first sampling (14 wk). The medium fertilizer concentration
      resulted in best root growth and highest absolute oil dissipation (18.4%) after
      22 wk The highest concentration produced best shoot growth and highest relative
      oil dissipation after 14 wk (10.5% less than unplanted control). In general,
      degradation of total oil and grease was higher in planted than in unplanted soil,
      but differences diminished toward the end of the experiment. Next to fertiizer
      quantity, its composition is an important factor to be further studied, including
      the form of available nitrogen (N-NO3- vs. N-NH4+). Field trials are considered
      indispensable for further phytoremediation studies, since greenhouse experiments
      produce particular water and nutrient conditions.

PMID- 16285413
TI  - Effects of arsenic species and concentrations on arsenic accumulation by
      different fern species in a hydroponic system.
AB  - Two hydroponic experiments were conducted to evaluate factors affecting plant
      arsenic (As) hyperaccumulation. In the first experiment; two As hyperaccumulators
      (Pteris vittata and P. cretica mayii) were exposed to 1 and 10 mg L(-1) arsenite
      (AsIII) and monomethyl arsenic acid (MMA) for 4 wk. Total As concentrations in
      plants (fronds and roots) and solution were determined In the second experiment
      P. vittata and Nephrolepis exaltata (a non-As hyperaccumulator) were exposed to 5
      mgL(-1) arsenate (AsV) and 20 mgL(-1) AsIIIfor 1 and 15 d. Total As and AsIII
      concentrations in plants were determined Compared to P. cretica mayii, P. vittata
      was more efficient in arsenic accumulation (1075-1666 vs. 249-627mg kg(-1) As in
      the fronds) partially because it is more efficient in As translocation. As
      translocation factor (As concentration ratio in fronds to roots) was 3.0-5.6 for
      P. vittata compared to 0.1 to 4.8 for P. cretica. Compared to N. exaltata, P.
      vittata was significantly more efficient in arsenic accumulation (38-542 vs. 4.8
      71 mg kg(-1) As in thefronds) as well asAs translocation (1.3-5.6 vs. 0.2-0.5).
      In addition, P. vittata was much more efficient in As reduction from AsV to AsIII
      (83-84 vs. 13-24% AsIII in the fronds). Little As reduction occurred after 1-d
      exposure to AsV in both species indicates that As reduction was not instantaneous
      even in an As hyperaccumulator. Our data were consistent with the hypothesis that
      both As translocation and As reduction are important for plant As
      hyperaccumulation.

PMID- 16285415
TI  - [Public health in 2005: new stakes for the French Society of Public Health].

PMID- 16285414
TI  - Metal phytoextraction--a survey of potential risks.

PMID- 16285416
TI  - [Tobacco, alcohol and psychotropic drugs in Lorraine, epidemiological survey of
      the general population].
AB  - The aim of this study is to determine the prevalence of the use of tobacco,
      alcohol and psychotropic drugs by the people of Lorraine and characterise the
      consumption behaviours of that population. The sample consisted of 6571 people
      from the ages of 18 to 74 who were randomly selected from the telephone directory
      and were interviewed through the use of a self-questionnaire sent out by mail.
      The behaviours vary according to sex and gender. Tobacco is the product with the
      highest prevalence rate of consumption. This rate decreases with age and is most
      frequent in sectors of the population who are less educated, holding low or
      poorly skilled jobs or unemployed. Excessive alcohol consumption is observed in
      13.8% of men and 3.8% of women. Regular consumption of psychotropic drugs is two
      times higher in women than in men, and it increases with age. Women who are
      single, divorced or widowed are at the most risk, as are those who are not
      engaged in any professional activity. The prevalence of the consumption of psycho
      active licit toxic substances in the Lorraine population differs little from the
      national French average as far as men are concerned, yet appears to be higher for
      women. These results are very useful for regional prevention activities such as
      those within the Regional Health Programmes framework.

PMID- 16285417
TI  - [Measuring iron levels relative to the type of milk consumed within a population
      of 16 to 18 month old French infants].
AB  - The aim of this work was to study the consumption of different kinds of milk by a
      population of 16-18 month old children, and to compare the iron deficiency
      prevalence with the type of milk consumed. The study was carried out in 2002, and
      it involved 588 children who underwent medical check-ups at a social insurance
      paediatric clinic in Paris. Blood samples were collected from all of the
      participating children. 55% of the children drank iron-enriched milk, and this
      percentage increases in children who come from a higher level of socio-economic
      status and environment. The consumption of iron-enriched milk is a major factor
      in the protection against iron-deficiency anaemia and depleted iron supplies. The
      results suggest that much greater efforts are required for improving prevention
      programmes and initiatives, particularly in socially vulnerable or marginalised
      populations.

PMID- 16285418
TI  - [Models for calculating the cost of operational expenditure for a health centre
      in Senegal].
AB  - The transformation of a health post into a health centre generates new services
      which mobilise different resources. The objective of this work is to propose a
      budgetary forecasting model for this specific type of case, one which is
      recurrent although seldom documented. As a preliminary step, the quarterly
      operational costs were determined, and the "complete costs method" (or the
      homogeneous sections method) was utilised for this purpose. In the second phase,
      the "pre-established costs method" was used to set the budget forecasts. The
      amount to be recovered by the health committee for a three month period of
      operation is estimated at 1,574,967 F CFA (equivalent to approximately 2,400
      Euros), representing 42% of the total cost. The states assures the contribution
      of public funds to cover 54.2% of the cost, and the commune of Kanel furnishes
      3.8% of the total cost, however only in the form of in-kind contributions or
      other material resources. The overall estimated budget for the year 2004 is
      estimated at 14,835,425 F CFA (about 22,615 Euros) of which 57.6% is expected to
      be received from the state.

PMID- 16285420
TI  - [Health and human rights: perceptions of health professionals and human rights
      defenders].
AB  - A self-administered questionnaire served as the basis for a study carried out
      between February and June 2003 covering a panel of 125 experts from 33 countries
      spread over 5 continents. The objective of this study was to identify the human
      rights problems perceived as having a very negative health impact from
      approximately fifty proposals. This study also aimed at identifying the variables
      which could explain the differences in the perceptions observed. At the global
      level, the threats to physical integrity and attacks on human life, economic
      problems of a health or social nature, questions of political or democratic
      origin, as well as a wide spectrum of other problems are perceived as having very
      harmful effects on health with an average adhesion rate of severity (TMAG)
      ranging from 90-75%. For the same categories of problems at the national level,
      the TMAG varies from 67-40%: The observed consensus around the severity of human
      rights problems is tempered by the differences in perceptions according to
      profession, sex, and the level of the country's and continent's development.
      Other than the fact that these results corroborate the shared international
      concerns with regard to the state of the world's human rights, they suggest that
      the experts' opinions constitute a complementary source of information necessary
      for work on the international mechanisms for the surveillance of the
      implementation of international treaties; while at the same time, they indicate
      priorities for action in the field of public health and human rights.

PMID- 16285419
TI  - [Social vulnerability of out-patients consulting the dentistry service of a
      public hospital].
AB  - There are social inequalities in oral and dental health. It can be useful to
      identify people in socially vulnerable or marginalised situations because they
      require a particular kind of care. Through a survey of patients in a dentistry
      services in a public hospital, we sought to identify those people in a precarious
      socio-economic situation by the use of a tool designed and validated by multi
      disciplinary experts. The tool includes five criteria, and is presented in the
      format of an index card which is filled in by the patient upon his arrival. This
      data collection was carried out in two distinctly separate period of time (winter
      and summer). 865 cards were collected, and the rate of collection of complete
      data was 73%. 94% of the cards allowed us to determine the socio-economic status
      of the patient, and 48% (n=382) of them were classified as having a socially
      vulnerable situation. Among them, 69% of them benefited from CMU or AME, and 59%
      of them do not have any supplementary health insurance. 47% of them admit to
      having difficulties in paying for their medications or covering the cost of their
      medical consultations, and 48% perceive a social service aide. The prevalence of
      social vulnerability of the dental centre's patients is estimated at 32%. This
      data collection tool has made it possible to measure the significance and the
      nature of the social vulnerability of the patients who receive care and services
      from this public hospital's dentistry unit. Its capacity to identify patients
      whose care needs are often not met remains to be seen, as well as the capacity of
      the hospital to make up for these lost opportunities thus remains to be
      highlighted.

PMID- 16285421
TI  - [Nurses experiencing burn out in psychiatry: from research to the hospital
      setting].
AB  - A purely managerial approach to burn out amongst nursing staff within a hospital
      setting, for instance, through the use of psychometric scales to measure the
      phenomenon, may implicitly lead to a singular focus on the vulnerability of the
      personnel concerned. Far from being a purely natural phenomenon, burn out should
      not be perceived as such, but rather it should be viewed in terms of how it
      relates to the ambiguity between the various professional sub-cultures of the
      different partners involved in the domain of care provision. In fact, burn out is
      socially constructed. It is not interpreted in the same way across all contexts,
      and varies for example when nurses speak about their personal challenges and
      difficulties associated with administering and performing their professional
      duties, or when their union representatives speak on their behalf to claim rights
      or create better conditions in their working environment, or when psychological
      researchers use the term. It is important to note that these different contexts
      influence how the term is construed, and scientific standardisation of such a
      term irrespective of the context in which it is used can lead to great
      misunderstanding. Burn out should be considered as referring to anthropological
      representations, that are either shared or not, between different health care
      professionals when they meet at the crossroads where interactions and exchanges
      occur between their professional culture and the general culture of the society
      at large.

PMID- 16285422
TI  - [Applying social network analysis to the health system].
AB  - BACKGROUND: Social network analysis is a method for describing and
      contextualising the structural relationships amongst social entities. The aim of
      this study was to assess the relationships between hospitals through the use of
      an example of a hospital that takes care of myocardial infarction in the region
      of Provence Alpes Cote d'Azur (PACA). METHOD: This retrospective study included
      all patients hospitalised for acute coronary syndrome in the PACA region between
      January and June 2000. The description analysis consisted of making a graph
      describing the transfer of patients between hospitals to calculate indicators for
      the centrality of the hospital and its prestige. The graph was also used to
      determine and measure the sub-group cohesion (cliques) and the density of the
      hospital network. RESULTS: A total of 2049 patients suffering from myocardial
      infarction were admitted to 78 hospitals during the study period. There were 867
      transfers from one hospital to another. 51 cliques were highlighted; 29 hospitals
      do not belong to a clique. Among the 49 hospitals who do belong to sub-groups,
      50% are linked to two cliques. Eight hospitals belong to more than 8 sub-groups,
      and the maximum number of sub-groups to which a hospital is linked is 12. The
      density of the hospital network is 0.12. CONCLUSIONS: Social network analysis is
      a field of research open and adaptable to the public health scene. This method
      could be applied to the evaluation of health and hospital administration and
      management networks.

PMID- 16285423
TI  - [Cultural diversity in Montreal: a range of public health challenges].
AB  - Increasing immigration to Quebec has brought to the surface the need for adapting
      its public health systems and services, particularly in the area of primary care.
      The challenge is to take the heterogeneous nature of the population into account
      and to integrate diverse values, experience and know-how into the development of
      programmes and delivery of services, whilst simultaneously respecting the values
      of the various care providers and the norms of the institutions in the host
      country. This article addresses the question of adaptation strategies for health
      services, and namely the development of prevention and heath promotion programmes
      in public health within the framework of primary health care services within the
      intercultural context of Montreal. The issue of adaptation falls within the
      perspective and mandate of the Quebec government's policy on health and well
      being (La politique de sante et du bien-etre, 1992). Furthermore, it is a
      response to frequent demands from various health professionals and groups
      concerned with the adaptation of public services with respect to intercultural
      relationships confronted with the emerging realities associated with immigration.
      The article provides a reflection on specific ways of adapting prevention and
      health promotion initiatives targeting cultural communities and those who are
      undergoing immigration procedures or transitions. It also examines the
      development of ethno-cultural or other indicators which make it possible to
      capture migration experiences and their health impact. Since the Quebec health
      and social services system is currently in the process of major reform, it is
      hoped that it will seize this opportunity in order to make health and social
      service centres accountable for the adaptation of their programmes and services
      to the diversity of the populations they serve.

PMID- 16285424
TI  - [Adolescent mental health: perception and support from adults in the school
      setting].
AB  - OBJECTIVE: To compare young people's and adult's perceptions of certain mental
      health issues in order to be able to propose solutions targeting the improvement
      of the current situation. METHOD: A school nurse, a chief education counselor and
      homeroom teacher (3 people per establishment) from 15 schools in the Doubs county
      were questioned using semi-directed interviews. The schools were all junior high
      schools or preparatory schools for students aged between 15 and 18 who were
      studying to take the baccalaureat examination. The data were compared with those
      of the Health Barometer (a national representative sample of young people
      attending school in France). RESULTS: Adults have a different perception of
      health in general and mental health in particular compared to that of young
      people. There is a perceptible gap between certain adults on the one hand, given
      their motivation, investment and wish be of help to young people, and on the
      other hand, young people's perception of it. It seems that for everyone
      questioned, the school nurse is a uniquely, important contact person. She is in a
      considerably favourable position for listening and providing assistance on
      difficult questions like suicidal thoughts, depression, and problems linked to
      sexuality or contraception.

PMID- 16285426
TI  - [Prevention of work-related muscular-skeletal disorders of upper limbs: a social
      challenge and economic obligation].
AB  - Work-related muscular-skeletal disorders of upper limbs (WRMSDul) represent 66%
      of all occupational injuries and diseases (OD). The total number of cases has
      multiplied by 8 over the past eleven years, and in 2002 there were 21126 OD
      incidents recorded. Although OD statistical data are not necessarily a truly
      precise reflection of the reality of associated risks, examination of these
      trends shows that over the past 10 years the most serious diseases, like rotator
      cuff tendonitis, have increased more rapidly than have the totality of WRMSDul
      cases as a whole. It is likely that the number of injured workers will continue
      to increase over the course of the coming years. An evaluation of indirect costs
      also demonstrates that there are significant social consequences associated with
      these diseases and which put into question the employability of the affected
      workers, who are often aged between 40 and 60 years old. This paper therefore
      brings to the surface the importance of prevention principles and proposes an
      ambitions prevention plan. This emblematic occupational health risk will
      constitute, along with professionally related cancers, one of the major
      challenges for prevention in the coming years.

PMID- 16285425
TI  - [Networking of documentation practices in health education committees].
AB  - A national network of health education information officers was established at
      the end of 2001. The aim and objective of this group is "to contribute to the
      development of a solid, coherent documentation service delivery for the health
      education field in France." The professionals decided to commence by undertaking
      an assessment of the documentation activities in both the regional and
      departmental health education committees in order to establish sub-working groups
      which would collaborate to better achieve this goal. The survey's results have
      shown that there are existing skills and competencies available within the
      different committees in spite of current gaps between the various regions and
      department in terms of their levels of qualifications, resources and information
      activities and practices. It is for this reason that the national network of
      health education information officers designed and implemented the smaller
      working groups in order to gradually enable them to solidify and strengthen the
      network to ensure that they have the capacity to meet the stated objectives. This
      approach could constitute the basis for a national health education documentation
      network as described and called for by the law delineating the missions of the
      French Institute for Prevention and Health Education (Inpes).

PMID- 16285427
TI  - [Nosocomial infections: revisiting history to think about the present].

PMID- 16285428
TI  - [School health municipal service and health promotion in Villeurbanne].
AB  - A school health municipal service has been in existence in Villeurbanne since its
      creation in 1935. It works throughout the city's schools, and in particularly in
      places which provide the last year of nursery school and all primary-level
      schools as well. In 1998 it was integrated into the office of the Directorate for
      Hygiene and Public Health, which provided an opportunity to reconsider its
      mission and reflect upon the priorities. The balance between screening and
      prevention was examined. Furthermore, its approach to thematic issues was put
      into question given the lack of a strategic overall programming methodology. The
      new health policy aimed at students was executed through a reorganization of
      evaluations, leading to the creation and implementation of a new programme called
      "I take care of myself" specifically targeting all first grade children. The
      results of this programme, which focuses on the development of a more
      comprehensive approach, are encouraging. Thanks to the programme, health has been
      reinstalled in its proper place in the schools, and it has become a matter of
      great importance for the children, their parents and the teachers. Furthermore,
      the school health service has consolidated and strengthened its role in this
      manner.

PMID- 16285429
TI  - [The community health centre of Cherbourg-Octeville].

PMID- 16285430
TI  - [Mental health plan: the story of a common urban reality].

PMID- 16285431
TI  - [Physiopathological mechanisms in tinnitus generation and persistence].
AB  - Progress in neuroscience research has given birth to new theories for tinnitus
      generation. From a point of view where cochlear dysfunctions would be considered
      as the origin and maintenance mechanisms, it has been introduced the important
      role of compensation systems from the central auditory pathways. They could act
      as the most relevant factor for chronic persistent tinnitus after a peripheral
      aggression. Unmasking of silent synapses or sprouting of new ones activate
      cortical reorganization for frecuencial areas nearby the non-stimulated ones
      through brain plasticity. Connections to associative cortex and limbic-amigdala
      area using the non-classical auditory system explain the presence of hyperacusis,
      anxiety or depression, factors that increase the severity of tinnitus.
      Implementation of these physiopathological theories reinforces the tinnitus
      neurophysiological model. The development of an aversive response through the
      survival reflex and the participation of negative emotional response are the
      responsible for signal persistence and vegetative reactions from the autonomous
      nervous system. Implications of this knowledge for tinnitus treatment involve the
      central auditory system approach through the combination of medical counselling
      for reduction of the aversive reaction and sound therapy to diminish its
      perception.

PMID- 16285432
TI  - [Cochlear implant in congenital malformations].
AB  - OBJECTIVE: The main objective is to evaluate the complications and problems
      encountered in a population with inner ear congenital malformation undergoing
      cochlear implantation. MATERIALS AND METHODS: The present study includes 33
      patients with congenital inner ear malformation, from a total population of 346
      cochlear implant patients, implanted from February 1993 to March 2004.
      Radiological evaluation and neurological exams were performed to all these
      patients in order to evaluate all the preoperative conditions. RESULTS: The most
      common cochlear anomalies we found were: cochlear hypoplasia, Incomplete
      partition and Common cavity (n=15). In 4 cases an enlarge aqueduct was also
      associated to the cochlear anomaly. We also found 6 cases with labyrinthine
      anomalies. The surgical procedure was performed in 23 cases, and in 18 of them we
      obtained an electrical stimulation of the neural elements. CONCLUSIONS: There are
      no differences between patients with Incomplete Partition of the cochlea and mild
      Cochlea hypoplasia, if compared with those with normal cochlea. Severe
      malformations as Common Cavity or severe hypoplasia may have a higher rate of
      surgical complications and the outcome cannot be predicted.

PMID- 16285433
TI  - [Vestibular evoked myogenic potential: a contribution to the vestibular
      physiology and pathology knowledge. Quantitative patterns in healthy subjects].
AB  - INTRODUCTION: Vestibulocollic reflex is a muscular reflex which is activated by
      acoustic stimulation. It shows two components: the first one, the vestibular
      evoked myogenic potential (VMEP) related to the vestibular pathway and the
      second, to the auditive pathway. The VMEP potential could be useful for
      vestibular physiology and pathology knowledge. OBJECTIVE: To determine the VMEP's
      parameters of normality and to evaluate influential factors such as age, sex or
      stimulation intensity. MATERIAL AND METHODS: Prospective study of the VCR in 40
      healthy individuals, distributed in 4 groups according to their age. Stimulation
      was carried out at 100db and 85db on each ear independently. RESULTS: There are
      not differences between both ears and sexes. Normal latency levels must be
      separated between two groups of age: older and younger than 11 years old. Normal
      absolute values of amplitude response differ depending on muscular contraction,
      age and stimulation intensity. It is more representative to consider the
      difference between the values obtained in the two ears of the same individual
      than to consider the absolute values.

PMID- 16285434
TI  - [Postural control related to age in patients with benign positional paroxysmal
      vertigo].
AB  - OBJECTIVE: To study the relationship between age and posturography in patients
      with benign positional paroxysmal vertigo. MATERIAL AND METHODS: Prospective
      study performed in 65 patients with benign positional paroxysmal vertigo (BPPV)
      in any variant. Sensory Organization Test outcomes were recorded and compared
      with their equivalents in a control group by means of scatter-plot diagrams and
      regression line. For statistical study, Mann-Whitney's U-test was used. RESULTS:
      Slope for regression lines in composite was -0.0934 in group NORMAL; in group
      BPPV it was -0.4284. This difference is due to conditions 5 and 6. Results were
      statistically significative. CONCLUSIONS: BPPV patients have a worse postural
      control than control group. The difference is bigger the older the patient is. It
      is due to a failure in conditions 5 and 6, so it should be from a vestibular
      origin.

PMID- 16285435
TI  - [Prognostic factors in adenoid cystic carcinoma of salivary glands].
AB  - OBJECTIVE: Adenoid cystic carcinoma (ACC) is a relatively rare tumor which is
      characterized by its long clinical history, with multiple recurrences and late
      distant metastasis. The aim of the present study is to show our experience in the
      management of this tumor and the relationship of different clinico-pathological
      parameters with its prognosis. MATERIAL AND METHODS: A retrospective study was
      carried out between 1984 and 2004 in 28 patients with ACC of the salivary glands,
      analyzing the most outstanding clinico-pathological variables in this tumor
      related to the prognosis of the tumor and the survival. RESULTS: The overall
      survival rates at 5, 10 and 15 years were 88%, 69% and 52% respectively. Ten
      (36%) patients presented local recurrence and 10 (36%) presented distant
      metastasis (four of which also have local recurrence). Although the differences
      were not statistically significant, the patients with solid histological subtype
      (p=0.17), with positive margins status (p=0.2), with perineural invasion
      (p=0.59), and those treated with surgery alone (p=0.19), presented a worse
      survival. DISCUSSION/CONCLUSION: Our study confirms that the ACC is a tumor with
      a high tendency to local recurrence and development of distant metastasis, even
      long term, which means a close follow-up for life. Nevertheless, it also
      demonstrates that acceptable survival rates can be obtained with aggressive
      treatment.

PMID- 16285436
TI  - [The role of radiotherapy in the management of bucopharyngeal epidemic Kaposi's
      sarcoma].
AB  - PURPOSE: This study is presented to help define the role of radiotherapy in the
      management of buccopharyngeal epidemic Kaposi's sarcoma. MATERIAL AND METHODS:
      Between January 1999 and December 2004, we treated 17 patients who had acquired
      inmunodeficiency syndrome related to mucous Kaposi's sarcoma. Kaposi's sarcoma
      lesions were in the oral cavity in 12 patients (70%), oropharynx in 3 patients
      (18%) and larynx in 2 patients (12%). All the patients were treated by
      radiotherapy using a Cobalt Unit beam energy, the treatment doses ranged from 15
      to 30 Gy. RESULTS: Tolerance was generally satisfactory, with an effective
      palliation of symptoms (88,4% overall rate of objective responses). Nevertheless
      an enhanced mucosal reaction was noted in patients receiving doses close to 30 Gy
      (mucositis grade 3). CONCLUSIONS: We conclude that radiotherapy is an efficient
      treatment for mucous epidemic Kaposi's sarcoma; a dose of 15 Gy may be enough to
      shrink the tumour and obtain a good palliation of symptoms. Prophylactic measures
      with antifungal treatment should be systematically associated with oropharyngeal
      irradiation in order to improve tolerance to the treatment.

PMID- 16285437
TI  - [Nasal malignant meningioma].
AB  - Extracraneal meningiomas represent 2% of all meningiomas and can appear in
      different locations including paranasales sinuses. There are no statistics
      regarding ectopic malignant meningiomas, but they are considered extremely rare.
      Due to this, there is no management protocol. We present a patient with a
      malignant meningioma of the etmoidal sinus, his treatment and the evolution over
      a five year period.

PMID- 16285438
TI  - [Toxic shock syndrome associated with nasal packing].
AB  - Staphiloccocal Toxic Shock Syndrome is a potentially fatal multisystem disease
      associated to nasal packing, catheter insertion, retention of foreign materials
      and uneffective sterile techniques. It is usually developed in the immediate
      postoperative period (first 48 hours) with hypotension, skin rash, fever,
      multisystemic failure and shock. We report a case in a 24-year-old man secondary
      to nasal surgery.

PMID- 16285439
TI  - [Cochlear implants in Aragon].
AB  - Cochlear implants are, actually, one of the major advances in the treatment for
      profound deafness. His use is, already, a routine in the daily practice of our
      specialty. Due to its special aspects, cochlear implants have to be done
      following a protocol that organizes and coordinates the different aspects of the
      diagnoses and treatment of profound deafness, in the different administrative and
      geographical fields. The health system in our country and the smale dimension of
      our area, has taken us to create and follow a special program in which all the
      available resources are used. Following this protocol, we have performed 63
      cochlear implants, in the last 10 years. We show here the results and
      complications.

PMID- 16285440
TI  - Multistage chemical etching for high-precision frequency adjustment in ultrahigh
      frequency fundamental quartz resonators.
AB  - Chemical etching to precisely adjust and to make uniform the thicknesses of
      vibrating areas of multiple resonators in a single wafer was applied to inverted
      mesa quartz resonators exciting an ultrahigh-frequency fundamental thickness
      vibration. The process consisted of five stages, combining high-rate etching for
      high productivity and low-rate etching for high-precision adjustment. By using
      this process, the resonance frequencies of 41 resonators in the single wafer were
      adjusted to 620 +/- 1.5 MHz, which corresponds to vibrating area thicknesses of
      2.2 microm +/- 6 nm. In the temperature-frequency characteristics of these
      resonators in the single wafer, the difference between the maximum first-order
      temperature coefficient and the minimum first-order temperature coefficient was
      equivalent to a cut angle change of two arcminutes. In addition, vibrating areas
      with an arithmetic mean surface roughness of 0.17 nm on the concave side were
      produced by this multistage etching.

PMID- 16285441
TI  - High Q-factor microwave Fabry-Perot resonator with distributed Bragg reflectors.
AB  - A Fabry-Perot resonator operating at 39 GHz, with two pairs of quarter-wavelength
      single-crystal quartz Bragg reflectors has been realized. For the length of 98.26
      mm, its Q-factor is about 560,000, which is 4.3 times better than for the same
      resonator without Bragg reflectors. Rigorous finite-difference frequency-domain
      analysis has been applied to the problem and is compared with simplified semi
      analytical solutions. Good agreement between theoretical and experimental
      resonant frequency and Q-factors has been obtained. Thermal compensation of the
      resonant frequency of the Fabry-Perot has been proposed employing rods and
      cylinders made of metals with different thermal expansion coefficients.

PMID- 16285442
TI  - Evaluation of Kalman filtering for network time keeping.
AB  - Time information is critical for a variety of applications in distributed
      environments that facilitate pervasive computing and communication. This work
      describes and evaluates a novel Kalman filtering algorithm for end-to-end time
      synchronization between a client computer and a server of "true" time [e.g., a
      Global Positioning System (GPS) source] using messages transmitted over packet
      switched networks, such as the internet. The messages exchanged have the network
      time protocol (NTP) format, and the algorithm evaluated, is performed only at the
      client side. The Kalman filtering algorithm is compared to two other techniques
      widely used, based on linear programming and statistical averaging, and the
      experiments involve independent consecutive measurements (Gaussian case) or
      measurements exhibiting long-range dependence (self-similar case). Performance is
      evaluated according to the estimation error of frequency offset and time offset
      between client and server clock, the standard deviation of the estimates and the
      number of packets used for a specific estimation. The algorithms could exploit
      existing NTP infrastructure, and a specific example is presented.

PMID- 16285443
TI  - Quantum 1/f effect in resonant biochemical piezoelectric and MEMS sensors.
AB  - Piezoelectric sensors used for the detection of chemical agents and as electronic
      nose instruments are based on bulk and surface acoustic wave resonators.
      Adsorption of gas molecules on the surface of the polymer coating is detected by
      a reduction of the resonance frequency of the quartz disk, subject also to
      fundamental quantum 1/f frequency fluctuations. The quantum 1/f limit of
      detection is given by the quantum 1/f formula for quartz resonators. Therefore,
      for quantum 1/f optimization and for calculation and improvement of the
      fundamental sensitivity limits, we must avoid closeness of the crystal size to
      the phonon coherence length, which corresponds to the maximum error and minimal
      sensitivity situation, as shown here. Adsorbed masses below the pg range can be
      detected. Microelectromechanical system (MEMS) resonators have provided a
      possibility for the nanominiaturization of these sensors. Essential for
      integrated nanotechnology, these resonant silicon bars (fingers) are excited
      magnetically or electrically through external applied forces, since they are not
      piezoelectric or magnetostrictive. The application of the quantum 1/f theory to
      these systems is published here for the first time. It provides simple formulas
      that yield much lower quantum 1/f frequency fluctuations for magnetic excitation,
      in comparison with electrostatically driven MEMS resonators.

PMID- 16285444
TI  - Limitations on the use of the power-law form of Sy(f) to compute Allan variance.
AB  - An exact solution to the well-known integral transform that relates the spectral
      density of the instantaneous fractional frequency deviation, Sy(f), to the Allan
      variance, sigma2y(tau), is presented for the case of a power-law representation
      of Sy(f). The approximate solution to this integral transform, which is found
      throughout the literature, also is derived. A graphical convergence analysis is
      presented, showing the range of applicability of the approximate solution. The
      results reinforce the use of the approximate solution, which converges quickly to
      the exact solution under virtually all reasonable measurement conditions.

PMID- 16285445
TI  - Computer simulation of forward wave propagation in soft tissue.
AB  - A method for simulating forward wavefront propagation in heterogeneous tissue is
      discussed. The intended application of this method is for the study of aberration
      produced when performing ultrasound imaging through a layer of soft tissue. A one
      way wave equation that permits smooth variation in all acoustically important
      variables is derived. This equation also describes tissue exhibiting nonlinear
      elasticity and arbitrary frequency-dependent relaxation. A numerical solution to
      this equation is found by means of operator splitting and propagation along the
      spatial depth coordinate. The numerical solution is accurate when compared to
      analytical solutions for special cases, and when compared to numerical solutions
      of the full wave equation by other methods. The presented implementation provides
      a fast numerical method for studying the impact of aberration in medical
      ultrasound imaging through soft tissue--both on the transmitted beam and the
      nonlinearly generated harmonic beam.

PMID- 16285446
TI  - Piezoelectric contrast materials for ultrasound imaging.
AB  - Piezoelectric ceramics and polymers can be used as a type of marker and contrast
      material for medical ultrasound imaging systems. High-frequency electrical
      signals are detected from surface electrodes when these materials are introduced
      into conducting media such as tissue and scanned by ultrasound imaging systems.
      Detected signals are applied to the imaging circuits of a modified ultrasound
      system such that they display a unique type of electrical image that shows the
      piezomaterial's polarization, shape, and position at arbitrarily high contrast
      compared to the conventional ultrasound acoustic image. The resulting
      piezoelectric image can be merged in real-time with conventional ultrasound
      acoustic imaging to form a composite image. This approach is of interest in the
      development of improved techniques for imaging medical devices that are implanted
      or otherwise introduced into the body.

PMID- 16285447
TI  - Building three-dimensional images using a time-reversal chaotic cavity.
AB  - The design of two-dimensional (2-D) arrays for three-dimensional (3-D) ultrasonic
      imaging is a major challenge in medical and nondestructive applications.
      Thousands of transducers are typically needed for focusing and steering in a 3-D
      volume. In this article, we propose a different concept allowing us to obtain
      electronic 3-D focusing with a small number of transducers. The basic idea is to
      couple a small number of transducers to a chaotic reverberating cavity with one
      face in contact with the body of the patient. The reverberations of the
      ultrasonic waves inside the cavity create at each reflection virtual transducers.
      The cavity acts as an ultrasonic kaleidoscope multiplying the small number of
      transducers and creating a much larger virtual transducer array. By exploiting
      time-reversal processing, it is possible to use collectively all the virtual
      transducers to focus a pulse everywhere in a 3-D volume. The reception process is
      based on a nonlinear pulse-inversion technique in order to ensure a good
      contrast. The feasibility of this concept for the building of 3-D images was
      demonstrated using a prototype relying only on 31 emission transducers and a
      single reception transducer.

PMID- 16285448
TI  - An integrated semicompliant balloon ultrasound catheter for quantitative feedback
      and image guidance during stent deployment.
AB  - An integrated balloon ultrasound catheter prototype was designed to image from
      inside the balloon for real-time guidance during stent deployment. It was
      fabricated using a semicompliant balloon material (polyethylene) and a 20 MHz, 64
      element circumferential ultrasound array. A commercial stent, nominally 4.4 mm in
      diameter and 12 mm in length, was used for a phantom study and placed along the
      length of the integrated balloon ultrasound catheter. A rubber phantom was
      created with an elastic modulus of 175 kPa with a 4.36 mm diameter lumen. Real
      time balloon pressure measurements were recorded using a digital pressure sensor,
      and real-time radio-frequency (RF) data were captured as the balloon was
      inflated. The slope of the area-pressure ratio (APR) was compared to a reference
      measure of the balloon and stent expanded in water to determine a measure for
      optimal stent deployment. The results clearly indicate stent deployment at 11.1
      atm using this metric. The APR slope could serve as quantitative feedback
      parameter for guiding stent deployment to reduce arterial injury and subsequent
      restenosis. After the stent deployment experiment, RF data were captured as the
      balloon catheter was moved along the length of the stent in pullback mode to
      confirm successful stent deployment. Ultimately, an integrated balloon ultrasound
      catheter could serve as a single catheter intervention device by providing real
      time intravascular ultrasound (IVUS) imaging and quantitative feedback during
      stent deployment.

PMID- 16285449
TI  - Spatial and temporal aberrator stability for real-time adaptive imaging.
AB  - Reported real-time adaptive imaging systems use near-field phase correction
      techniques, which are desired because of their simple implementation and their
      compatibility with current system architectures. Aberrator stability is important
      to adaptive imaging because it defines the spatial and temporal limits for which
      the near-field phase estimates are valid. Spatial aberrator stability determines
      the required spatial sampling of the aberrator, and temporal aberrator stability
      determines the length of time for which the aberration profile can be used. In
      this study, the spatial and temporal stability of clinically measured aberrations
      is reported for breast, liver, and thyroid tissue. Cross correlations between
      aberration estimates revealed aberrators to have azimuthal isoplanatic patch
      sizes of 0.44, 0.28, and 0.20 mm for breast, liver, and thyroid tissue,
      respectively, at 80% correlation. Axial isoplanatic patch sizes were 1.26, 0.76,
      and 1.80 mm for the same tissue, respectively, at 80% correlation. Temporal
      stability at 80% correlation was determined to be greater than 1.5 seconds for
      breast and thyroid tissue, and 0.65 seconds for the liver. The effects of noise,
      motion, and target nonuniformity on aberrator stability are characterized by
      simulations and experiments in tissue mimicking phantoms.

PMID- 16285450
TI  - Transcranial ultrasound focus reconstruction with phase and amplitude correction.
AB  - Therapeutic and diagnostic ultrasound procedures performed noninvasively through
      the skull require a reliable method for maintaining acoustic focus integrity
      after transmission through layered bone structures. This study used a multiple
      element, phased-array transducer to reconstruct ultrasound foci through the human
      skull by amplitude and phase correction. It was previously demonstrated that
      adaptive phase correction using a multiple-element, focused transducer array
      yields a significant correction to an acoustic field that has been distorted by
      the heterogeneities of the skull bone. The introduction of amplitude correction,
      in a regime in which acoustic pressures from individual transducer array elements
      are adjusted to be normalized at the focus, has demonstrated a 6% (-0.27 dB)
      average decrease in acoustic sidelobe acoustic intensity relative to the focal
      intensity and a 2% (-0.09 dB) average decrease in the full-width-at-half-maximum
      (FWHM) of the acoustic intensity profile at the focus. These improvements come at
      the expense of significant ultrasound intensity loss--as much as 30% lower (-1.55
      dB)--at the focus because the amplitude correction method requires that, at
      constant power, a larger proportion of energy is absorbed or reflected by regions
      of the skull that transmit less energy. In contrast, a second correction method
      that distributes pressure amplitudes such that the sections of the skull which
      transmit more ultrasound energy are exposed with higher ultrasound intensities
      has demonstrated an average sidelobe intensity decrease of 3% (-0.13 dB) with no
      change in the FWHM at the focus. On average, there was a 2% (0.09 dB) increase in
      the acoustic intensity at the focus for this inverse amplitude correction method.
      These results indicate that amplitude correction according to the transmission
      properties of various segments of the skull have a clear effect on ultrasound
      energy throughput into a target site within the brain parenchyma.

PMID- 16285451
TI  - HIFU focusing efficiency and a twin annular array source for prostate treatment.
AB  - A measure of focusing efficiency is introduced for high-intensity, focused
      ultrasound (HIFU). The measure consists of the fraction of the total acoustic
      power emitted that linearly propagates through a circle located at the focus. The
      medium is absorption-free water, and power is computed using pressure and the
      normal component of velocity. 3 MHz phased-array designs involving different
      element layouts and curvatures are placed in square apertures of length 2.2 cm.
      The acoustic fields of these devices then are propagated to on-axis foci. The
      resulting focal efficiencies then are calculated using a two wavelength (0.1 cm)
      radius circle. Among these array designs, an annular array with 27 wavelength
      wide rings then is extended to be the basis of a twin phased-array device for
      prostate hyperthermia treatment. The two annular arrays are attached to door-like
      hinges to allow for joint two-dimensional focusing. The focusing efficiency of
      this device then is compared to rectangular element-array devices with the same
      5.4 by 2.2 cm source extent. With the addition of absorption and finite-amplitude
      distortion, the heating rate and temperature rise produced by the twin annular
      device in prostate tissue is considered. As a final look at the potential of
      annular array-based designs, three larger 2 MHz devices are briefly considered
      for abdominal treatment.

PMID- 16285452
TI  - Transient response analysis of a Rosen-type piezoelectric transformer and its
      applications.
AB  - This paper investigates the characteristics of voltage transient response, such
      as the maximum voltage, direct current (DC) time constant, alternating current
      (AC) time constant and oscillation frequency, and their applications for a Rosen
      type piezoelectric transformer (PT). The transient response is induced
      immediately after an AC voltage connected to the PT is switched off. For the
      applications, the maximum voltage is used to elucidate how to cause an electrical
      shock for users of the PT under open-circuit operation. The DC time constant and
      the AC time constant are used to estimate the equivalent resistance of the
      mechanical loss and the dielectric resistance of the dielectric loss,
      respectively. Also, the AC time constant is used to estimate the quality factor
      of the PT. Additionally, the oscillation frequency is used as an antiresonant
      frequency of the PT. In order to verify the above characteristics and
      applications, both an equivalent circuit with initial conditions and a drive
      system with a control switch interposed between the PT and its AC voltage source
      are adopted to derive the transient response and measure its characteristics.
      Effects of the load resistance of the PT and the switching-off time of the
      voltage source on the transient response are measured and discussed.

PMID- 16285453
TI  - Measurement of spatial cross sections of ultrasound pressure fields by optical
      scanning means.
AB  - The measurement of spatial cross sections of ultrasound pressure fields is an
      essential element of exposimetry of ultrasonic medical equipment. An optical
      technique is presented that allows the two-dimensional (2-D) determination of
      ultrasound pressure using an optical multilayer hydrophone in which a laser beam
      with suitable wavelength is partially reflected from a dielectric optical
      multilayer system. By detecting the change in reflectivity of the multilayer
      coating induced by the incident ultrasound, the pressure time waveform can be
      determined. A 2-D data acquisition covering an area of at least 15 mm x 5 mm was
      realized by two complementary approaches. A serial detection scheme was set up by
      scanning the sensing point across the area of interest by a micromechanically
      engineered scanning mirror and acquiring pressure time waveforms sequentially and
      pointwise. This allows the measurement of repeating ultrasonic waveforms with a
      spatial resolution of better than 70 microm and a minimal detectable pressure of
      50 kPa (bandwidth: 50 MHz) in a few seconds. In an alternative approach
      exploiting the parallel processing capabilities of a charge-coupled devices (CCD)
      camera chip, the probe was strobe-illuminated by a large-diameter collimated beam
      of a pulsed laser diode. The 2-D pressure distribution at a particular moment was
      derived from captured reflectivity distributions with a spatial resolution of 75
      microm. By successive delaying of the laser pulse with respect to the ultrasound
      pulse, the complete 2-D pulse waveform was acquired with high spatial resolution.
      Measurement results on ultrasound fields from plane and focusing transducers are
      presented and compared to simulation results. Individual advantages and drawbacks
      of both approaches are discussed. A combined setup merging both detection schemes
      into a single device was developed and represents a milestone on the way toward
      constructing an optical ultrasound measuring camera.

PMID- 16285454
TI  - Characterization of digital waveforms using thermodynamic analogs: applications
      to detection of materials defects.
AB  - We describe characterization of digital signals using analogs of thermodynamic
      quantities: the topological entropy, Shannon entropy, thermodynamic energy,
      partition function, specific heat at constant volume, and an idealized version of
      Shannon entropy in the limit of digitizing with infinite dynamic range and
      sampling rate. We show that analysis based on these quantities is capable of
      detecting differences between digital signals that are undetectable by
      conventional methods of characterization based on peak-to-peak amplitude or
      signal energy. We report the results of applying thermodynamic quantities to a
      problem from nondestructive materials evaluation: detection of foreign objects
      (FO) embedded near the surface of thin graphite/epoxy laminates using
      backscattered waveforms obtained by C-scanning the laminate. The characterization
      problem was to distinguish waveforms acquired from the region containing the FO
      from those acquired outside. In all cases the thermodynamic analogs exhibit
      significant increases (up to 20-fold) in contrast and for certain types of FO
      materials permit detection when energy or amplitude methods fail altogether.

PMID- 16285455
TI  - On the sensing and tuning of progressive structural vibration waves.
AB  - Progressive flexural waves can be generated only in finite structures by fine
      tuning the excitation and the boundary conditions. The tuning process eliminates
      the reflected waves arising from discontinuities and edge effects. This work
      presents and expands two new methods for the identification and tuning of
      traveling waves. One is a parametric method based on fitting an ellipse to the
      complex spatial amplitude distribution. The other is a nonparametric method based
      on the Hilbert transform providing a space-localized estimate. With these
      methods, an optimization-based tuning of transverse flexural waves in a one
      dimensional structure, a vibrating beam, is developed. Existing methods are
      designed for a single frequency and are based on either combining two vibration
      modes or mechanical impedance matching. Such methods are limited to a designated
      excitation frequency determined by a specific configuration of the system. With
      the proposed methods, structural progressive waves can be generated for a wide
      range of frequencies under the same given system configuration and can be tuned
      in real time to accommodate changes in boundary conditions. An analytical study
      on the nature of the optimal excitation conditions has been carried out,
      revealing singular configurations. The experimental verification of the sensing
      and tuning methods is demonstrated on a dedicated laboratory prototype. The
      proposed methods are not confined to mechanical waves and present a comprehensive
      approach applicable for other physical wave phenomena.

PMID- 16285456
TI  - Thermoacoustic tomography with integrating area and line detectors.
AB  - Thermoacoustic (optoacoustic, photoacoustic) tomography is based on the
      generation of acoustic waves by illumination of a sample with a short
      electromagnetic pulse. The absorption density inside the sample is reconstructed
      from the acoustic pressure measured outside the illuminated sample. So far
      measurement data have been collected with small detectors as approximations of
      point detectors. Here, a novel measurement setup applying integrating detectors
      (e.g., lines or planes made of piezoelectric films) is presented. That way, the
      pressure is integrated along one or two dimensions, enabling the use of
      numerically efficient algorithms, such as algorithms for the inverse radon
      transformation, for thermoacoustic tomography. To reconstruct a three-dimensional
      sample, either an area detector has to be moved tangential around a sphere that
      encloses the sample or an array of line detectors is rotated around a single
      axis. The line detectors can be focused on cross sections perpendicular to the
      rotation axis using a synthetic aperture (SAFT) or by scanning with a cylindrical
      lens detector. Measurements were made with piezoelectric polyvinylidene fluoride
      film detectors and evaluated by comparison with numerical simulations. The
      resolution achieved in the resulting tomography images is demonstrated on the
      example of the reconstructed cross section of a grape.

PMID- 16285457
TI  - A microscopic view on acoustomigration.
AB  - Stress-induced material transport in surface acoustic wave devices, so-called
      acoustomigration, is a prominent failure mechanism, especially in high-power
      applications. We used scanning probe microscopy techniques to study
      acoustomigration of metal structures in-situ, i.e., during the high-power loading
      of the device. Scanning acoustic force microscopy (SAFM) allows for the
      simultaneous measurement of the acoustic wavefield and the topography with
      submicron lateral resolution. High-resolution microscopy is essential as
      acoustomigration is a phenomenon that not only results in the formation of more
      macroscopic voids and hillocks but also affects the microscopic grain structure
      of the film. We present acoustic wavefield and topographic image sequences giving
      a clear insight into the nature of the film damage on a submicron scale. The 900
      MHz test structures were fabricated on 36 degrees YX-lithium tantalate (YX
      LiTaO3) and incorporated 420-nm thick aluminium (Al) electrodes. By correlating
      the acoustic wavefield mapping and the local changes in topography, we confirmed
      model calculations that predict the correspondence of damage and stress (i.e.,
      hillocks and voids) are preferentially formed in areas of high stress. The way
      the film is damaged does not significantly depend on the applied power (for
      typical power levels used in this study). Furthermore, acoustomigration leads to
      smoother surfaces via lateral grain growth. Another contribution to the grain
      dynamics comes from the apparent grain rotation in the highly anisotropic stress
      field of an acoustic wave. Thus, through in-situ scanning probe microscopy
      techniques, one can observe the initial changes of the grain structure in order
      to obtain a more detailed picture of the phenomenon of acoustomigration.

PMID- 16285458
TI  - In-plane P-SV waves from a piezoelectric strip actuator: exact versus effective
      boundary condition solutions.
AB  - A piezoelectric strip of finite width and thickness is placed on top of an
      isotropic elastic half space. It operates in actuator mode, and a time harmonic
      voltage is thus applied across it. The piezoelectric material is of type 6 mm
      oriented so that a two-dimensional (2-D) in-plane (P-SV) problem results. By
      Fourier series expansions, the problem is solved exactly, and this result is
      compared to the case when the piezoelectric strip is replaced by an effective
      boundary condition, which is derived by series expansions in the thickness
      coordinate in the piezoelectric strip. At low frequencies, the results agree very
      well, and this corresponds to the situation often met in practice. In general,
      the effective boundary condition should be much easier to apply, for example when
      a finite element method (FEM) program is used.

PMID- 16285459
TI  - Piezoelectric two-layer stacks of cellular polypropylene ferroelectrets:
      transducer response at audio and ultrasound frequencies.
AB  - Piezoelectric cellular polypropylene films, so-called ferroelectrets, are
      assembled in a stack with two active transducer layers. The stack is
      characterized with respect to its linear and quadratic response in a frequency
      range from 1 kHz to 80 kHz. A relatively smooth frequency response in the sound
      pressure level is found for the individual layers as well as for both layers
      driven in phase. The piezoelectric response of the two-layer stack is twice the
      response of an individual layer over a rather broad frequency range. Furthermore,
      the influence of the preparation conditions on the resonance frequency and the
      effect of the quadratic distortion on the radiated sound are investigated both
      for the individual transducer films in the stack and for the stack system as a
      whole.

PMID- 16285460
TI  - Characterization of high-frequency, single-element focused transducers with wire
      target and hydrophone.
AB  - In this paper, a wire-target technique was used for lateral beam profile
      measurements for a single-element, focused transducers in the very high-frequency
      range (35-60 MHz). Two wire targets made from 9-cm long tungsten wires with
      diameters of 8 microm and 20 microm were used as the pulse-echo targets to
      measure the lateral beam profiles at the focal plane of two single-element,
      focused transducers, a spherically focused 40 MHz transducer and a lens-focused
      in-house lithium niobate (LiNbO3) 60 MHz transducer. For comparison, measurements
      on the same transducers were performed by three small-aperture hydrophones with
      geometrical diameters varying from 37 microm to 150 microm. Tomographic
      reconstruction of the acoustic field from the spherically focused transducer also
      was conducted. Results obtained with the wire-target technique are comparable to
      those obtained with small-aperture hydrophones in characterizing lateral
      radiation patterns of a single-element, focused transducer in the high-frequency
      range (35-60 MHz). However, the wire-target method may overestimate pulse length
      because of the additional attenuation caused by the return path. Compared to
      small-aperture hydrophones, the wire-target technique is simpler and more cost
      effective. Its major advantage, however, is in the frequency range above 100 MHz
      in which commercial hydrophones are not yet available.

PMID- 16285461
TI  - A noncontact method for detecting acoustic emission using a microwave Doppler
      radar motion detector.
AB  - A noncontact method for detecting acoustic emission was developed, using a
      microwave Doppler radar detector and an active band-pass filter. A theoretical
      model was developed and a prototype sensor was built and tested. The prototype
      responds to acoustic emissions (AE), from pencil lead break tests, at ranges up
      to 1.5 feet.

PMID- 16285462
TI  - Mechanism of cochlear excitation at low intensities.
AB  - In order to assess the mechanisms of cochlear activation, the cochlear fluids of
      one cochlea of a guinea-pig (I) were coupled to those of a cochlea of a second
      guinea-pig (II) by means of a saline-filled narrow bore tube, the ends of which
      were placed in the fluids around the opened round windows of both cochleae, thus
      joining the two cochleae from two different animals into a single, larger,
      unsealed fluid system. In response to air-conducted sound stimulation of cochlea
      I, auditory nerve-brainstem evoked responses could be recorded in animal II, not
      only when the coupling tube was filled with saline, but also when it was filled
      with ultrasound gel (viscosity 100,000 greater than that of water), when there
      was a very large hole encompassing a relatively large expanse of the cochlear
      shell of animal I, and even when animal I was no longer alive. The necessary
      control experiments were performed. Therefore, it is suggested that at low
      stimulus intensities, the passive, incoming basilar membrane traveling wave may
      not activate the cochlea. Instead the fluid pressures (condensation/rarefactions)
      induced in the cochlear fluids by vibrations of the stapes footplate may be
      adequate to directly activate the outer hair cells, which then generate an active
      component of basilar membrane displacement.

PMID- 16285463
TI  - Connexins in hearing loss: a comprehensive overview.
AB  - Connexins are a family of transmembrane proteins that form gap junctions between
      adjacent cells and allow intercellular communication. Connexin proteins are
      involved in pathological conditions in humans, mainly in hearing loss,
      neurodegenerative disorders and skin diseases. The association between connexin
      proteins and the inner ear is well established. The abundant expression of
      connexins in the auditory system of the inner ear demonstrates their importance
      in inner ear development and the hearing process. Most compelling, there are over
      100 mutations in genes encoding connexins that are associated with deafness. Most
      prominent is the remarkable involvement of connexin 26 in hearing loss. Mutations
      in the gene GJB2, encoding connexin 26, are responsible for around 50% of genetic
      cases of severe to profound non-syndromic hearing loss in some parts of the
      world. Learning more about the connexin family in general and about connexin 26
      in particular can shed light on the pathogenesis of the inner ear and bring us
      closer to finding clinical solutions for the hearing impaired.

PMID- 16285464
TI  - Dysfunction of the auditory efferent system in patients with traumatic brain
      injuries with tinnitus and hyperacusis.
AB  - OBJECTIVES: Tinnitus, hyperacusis and difficulty listening in background noise
      are common symptoms reported by patients with traumatic brain injury (TBI). The
      aim of this study was to explore the function of the auditory system in TBI
      patients with and without auditory complaints but having normal pure-tone
      audiograms. METHODS: The study consisted of 24 TBI patients with and 10 TBI
      patients without auditory complaints. In addition, 15 normal controls were
      included in the study. The function of the auditory system was tested by
      recording transient otoacoustic emissions (TEOAE) during the presentation of
      increasing levels of white noise in the contralateral ear. RESULTS: Most of the
      TBI patients with auditory complaints (87%) showed absent or significantly
      reduced effect of the auditory efferent system as compared with the TBI patients
      without auditory complaints and to normal controls. However, the global amplitude
      of the TEOAE was significantly higher in TBI patients with auditory complaints
      compared to those without. CONCLUSIONS: Due to its role in peripheral and central
      auditory activity, dysfunction of the efferent system may be at least partially
      responsible for these auditory complaints. This study underscores the importance
      of testing and evaluating the functional integrity of the medial efferent system
      by an objective and non-invasive method in patients with TBI.

PMID- 16285465
TI  - Electrical stimulation levels and electrode impedance values in children using
      the Med-El Combi 40+ cochlear implant: a one year follow-up.
AB  - The present study was designed to follow changes in electrical stimulation levels
      and electrode impedance values (EIV) in children using the Med-El Combi 40+
      cochlear implant (CI) during the first 12 months of implant use. The maps of 24
      prelingually deaf children implanted at a mean age of 5.9 years (range 1-15.9
      years) using the TEMPO+ speech processor programmed with CIS+ strategy were
      examined at five time points: initial stimulation, and 1, 3, 6, and 12 months
      post-initial stimulation. Most comfortable levels (M) and electrode impedance
      values (EIV) were analyzed according to three cochlear segments: apical, medial,
      and basal. Results indicated a significant increase in M levels until the 3-month
      time point, thereafter stabilization was evident. Furthermore, M levels in the
      apical segment were lower than those in the medial and basal segments. EIV
      decreased from initial stimulation to the 3-month time point and was then stable
      through the study follow up. Interestingly, the finding of higher EIV in the
      apical segment may be attributed to the physical characteristics of the Med-El
      electrode. In conclusion, the pattern of stabilization of M levels found in the
      present study is similar to that reported for children using other devices. The
      data presented here may be useful as a guideline for programming M levels and
      monitoring EIV in infants and young children. They may further help clinicians to
      identify those children that fall outside the 'typical' range.

PMID- 16285466
TI  - Event related potentials (ERPs) and behavioral responses: comparison of tonal
      stimuli to speech stimuli in phonological and semantic tasks.
AB  - Event related potentials (ERPs) were recorded from 20 young subjects to auditory
      target stimuli while they were performing three different tasks, using an oddball
      paradigm: 1. Tones: Subjects were instructed to respond to a 1 kHz tone, and
      ignore a 2 kHz tone; 2. Phonological: Subjects were instructed to respond only to
      pseudowords that had a specific ending ('f"); 3. Semantic: Subjects were
      instructed to respond to words that belonged to a specific category (animals).
      EEGs were recorded from 19 electrode sites. Peak amplitude of the early component
      (N100) did not differ significantly across the three tasks, although N100 peak
      latency differed significantly across tasks. In contrast, the later endogenous
      component (P300) was stimulus- and task-dependent. P300 latency differed
      significantly across stimuli and tasks: 336 ms to target tones; 682 ms to the
      phonological targets; and 727 ms to target words in the semantic task. P300
      amplitude was significantly larger to tones than to speech stimuli. P300 peak
      amplitude recorded from electrode sites over the left hemisphere to the tonal
      target stimuli did not differ significantly from that recorded over the right
      hemisphere. In contrast, P300 amplitude recorded to both the phonological and
      semantic targets was significantly larger over the left hemisphere than over the
      right hemisphere at the parietal electrodes. The present results can contribute
      to our understanding of how humans process linguistic stimuli. These findings
      emphasize the importance of using similar experimental protocols when conducting
      broad comparisons of ERPs to a variety of stimuli and tasks.

PMID- 16285467
TI  - Cortical activity of children with dyslexia during natural speech processing:
      evidence of auditory processing deficiency.
AB  - Children with dyslexia have difficulties with phonological processing. It is
      assumed that deficits in auditory temporal processing underlie the phonological
      difficulties of dyslectic subjects (i.e. the processing of rapid acoustic changes
      that occur in speech). In this study we assessed behavioral and
      electrophysiological evoked brain responses of dyslectic and skilled reading
      children while performing a set of hierarchically structured auditory tasks.
      Stimuli consisted of auditory natural unmodified speech that was controlled for
      the parameter of changing rate of main acoustic cues: vowels (slowly changing
      speech cues: /i/ versus /u/) and consonant-vowel (CV) syllables (rapidly changing
      speech cues: /da/ versus /ga/). Brain auditory processing differed significantly
      between groups: reaction time of dyslectic readers was prolonged in identifying
      speech stimuli and increased with increased phonological demand. Latencies of
      auditory evoked responses (auditory event related potentials [AERPs]) recorded
      during syllable identification of the dyslectic group were prolonged relative to
      those of skilled readers. Moreover, N1 amplitudes during vowel processing were
      larger for the dyslectic children and P3 amplitudes during CV processing were
      smaller for the dyslectic children. From the results of this study it is evident
      that the latency and amplitude of AERPs are sensitive measures of the complexity
      of phonological processing in skilled and dyslectic readers. These results may be
      signs of deficient auditory processing of natural speech under normal listening
      conditions as a contributing factor to reading difficulties in dyslexia.
      Detecting a dysfunction in the central auditory processing pathway might lead to
      early detection of children who may benefit from phonetic-acoustic training
      methods.

PMID- 16285468
TI  - The effect of number of perceptual categories on identification functions of non
      speech stimuli and the relationship to categorization of Hebrew voicing.
AB  - Category boundary (CB) of Hebrew voicing on voice-onset time (VOT) continuum was
      found to be different from non-speech stimuli on tone-onset time (TOT) continuum.
      This is in contrast to data in English, thus suggesting that CB for speech
      stimuli may be determined not only by general auditory sensitivities but by
      additional factors that may be speech specific. The data in Hebrew voicing,
      however, can also be explained by the fact that in Hebrew voicing, two categories
      were available to the listener, whereas for the TOT stimuli there were three:
      leading, simultaneous and lagging temporal events. The purpose of the present
      study was to investigate the effect of number of perceptual categories on CB of
      non-speech analogs of voicing in Hebrew-speaking subjects and compare them to
      those obtained on a VOT continuum. Twenty-four Hebrew-speaking adults
      participated in this study. Stimuli consisted of (a) a two-tone complex continuum
      that varied in the relative onset time of the lower frequency tone, and (b) a /ba
      pa/ continuum which varied in VOT values similar to (a). The same TOT continuum
      was tested twice. In one, subjects identified TOT stimuli as belonging to one of
      three categories (TOT3): leading, simultaneous, or lagging; and in the other to
      two categories of TOT (TOT2): leading or lagging. VOT stimuli were labeled as
      /ba/ or /pa/. Results show that (1) when listeners were offered only two
      perceptual categories of temporal events, the pattern of identification functions
      matched one of the two functions shown for TOT3, and (2) the category boundary of
      VOT stimuli was similar for all subjects regarding the value calculated for TOT2.
      The present study supports the hypotheses that (1) CB of non-speech stimuli is
      not influenced by the number of perceptual categories available to the listener,
      and (2) different mechanisms may underlie the categorical perception of speech
      versus non-speech stimuli.

PMID- 16285469
TI  - Thresholds for perception of ripple depth in the passband of a low-pass filter.
AB  - Filters are often used in research related to speech and tone perception.
      Idealized filters with flat pass-bands, flat stop-bands, and infinitely steep
      rolloff are impossible to implement, thus practical filters often have a
      frequency response curve that has a certain degree of ripple, and always have
      finite rolloff. Despite this, there is a dearth of literature concerning the
      sensitivity of the ear to such artifacts. In the current study we examined the
      threshold of sensitivity to ripple depth in the pass-band of a digital low pass
      finite impulse response (FIR) filter. FIR filters are often used due to their
      lack of phase distortion, and due to the fact that their ripple depth can be
      closely controlled. Using an adaptive threshold detection paradigm, we found the
      threshold of noticeable ripple depth to be 2.7 dB (SD = 1.45) for filtered noise,
      and 4.89 dB (SD = 2.09) for a filtered chirp signal. This is significantly larger
      than the difference limen in intensity (DLI) for noise or pure tones. Notably,
      the threshold for filtered noise is significantly lower and more uniform across
      subjects, compared to the threshold for a filtered chirp signal. We conclude that
      these issues must be addressed when the necessity for filtering arises, though
      they cannot be considered independently of the signals themselves.

PMID- 16285470
TI  - Biological background and role of adiponectin as marker for insulin resistance
      and cardiovascular risk.
AB  - Adiponectin is a serum protein secreted by adipocytes and accounts for
      approximately 0.01% of total plasma protein. In healthy patient populations
      adiponectin can be found in concentrations of 7-12 mg/l. Unlike other adipocyte
      products, adiponectin correlates with decreased free fatty acid blood
      concentrations and reduced body mass index or body weight. Adiponectin protects
      from vascular diseases by inhibiting local proinflammatory signals, preventing
      preatherogenic plaque formation, and by impeding arterial wall thickening.
      Proinflammatory state and endothelial dysfunction are nominators of the metabolic
      syndrome, a complex set of risk factors including vascular and metabolic insulin
      resistance with hyperglycemia, hypertension, and dyslipidemia. Over the past
      years, thiazolidinediones, like rosiglitazone or pioglitazone, became known as a
      therapeutic option for patients suffering from the metabolic syndrome. It is
      considered that insulin sensitizers exert their benefit through indirect
      induction of adiponectin expression. Clinical studies have confirmed that
      treatment with thiazolidinediones may increase adiponectin concentrations in
      patients with type 2 diabetes independent from improvements in blood glucose
      control or parallel treatment with insulinotropic drugs. These findings suggest
      that adiponectin may have a diagnostic value and can be used especially for
      monitoring treatment success. This review summarizes recent biological and
      clinical data indicating that adiponectin may be the molecular link between
      obesity and insulin resistance and may serve as a biomarker for the metabolic
      syndrome.

PMID- 16285471
TI  - Evaluation of a new enzyme-linked immunosorbent assay for the determination of
      neopterin.
AB  - BACKGROUND: Determination of neopterin especially evaluated for use on the
      Behring ELISA Processor BEP III highly suited for the demands of blood donation
      screening in blood banks. METHODS: A new commercially available enzyme-linked
      immunosorbent assay (ELISA) was developed for the detection of neopterin, a low
      molecular-mass pteridine. Neopterin is produced by interferon-activated
      macrophages or monocytes during the activation of the cellular immune system in
      various diseases. In Austria testing of neopterin to detect cellular immune
      activation is mandatory since 1995. The former assay version has been used for
      the measurement of neopterin at the Medical University Graz. As a result of the
      cooperation with the blood bank in Graz and the Dade Behring company we have
      developed a new ELISA kit based on a special coating procedure. For comparison we
      performed measurements with the current IBL Neopterin ELISA version, the HPLC
      method and with the ELItest Neopterin ELISA (BRAHMS). The new assay is based on a
      simple assay procedure with two incubations of 1 h and of 30 minutes. RESULTS:
      Linear regression analysis showed a significant correlation to the HPLC method.
      The assay is accurate and precise. CONCLUSIONS: The above mentioned neopterin
      assay as an alternative method to other ELISA kits and the HPLC is highly suited
      for automation and was especially evaluated as a simple, rapid and reproducible
      version for the Behring ELISA Processor BEP III during this study.

PMID- 16285472
TI  - Complementing the patient: a complement component deficiency in a patient with
      recurrent infections and glomerulonephritis.
AB  - We present a case showing the investigation of a 7-year-old girl with empyema and
      glomerulonephritis whose "immunological" defect was a single complement component
      (C2) deficiency which prevented her from activating her classical complement
      pathway. A defect in complement function should be suspected in any patient with
      severe or recurring pyogenic infections. Investigations of "? immune deficiency"
      should always include tests to assess the patency of the patient's complement
      system.

PMID- 16285473
TI  - Serum estradiol after single dose hCG administration correlates with Leydig cell
      reserve in hypogonadal men: reassessment of the hCG stimulation test.
AB  - The hCG stimulation test with assessment of serum testosterone (T) is used for
      evaluation of testicular function. This retrospective study was undertaken to
      estimate the diagnostic value of stimulated estradiol (E2) levels in the
      assessment of Leydig cell function. Serum T and E2 before and after repeated
      daily hCG injections in 23 adult men with clinically suspected or established
      primary hypogonadism were studied. After hCG administration serum T increased
      gradually with peak levels after 72 hours (delta84%, p=0.003). In contrast, serum
      E2 concentrations reached their maximal levels 24 hours after the first injection
      (delta168%, p=0.001). Serum T and E2 responses were more attenuated in men with
      LH > or =17 IU/L as compared to men with lower LH levels. Peak E2 levels after 24
      hours correlated significantly with peak T levels after 3 days. We conclude that
      the increase in serum E2 levels 24 hours after a single hCG injection is an
      useful additional measure of Leydig cell function. Assessment of E2 increments
      would render the test procedure more practical, less time-consuming and more cost
      effective than assessing peak T levels after 72 hours.

PMID- 16285474
TI  - Detection and identification of significant ANAs in previously determined ANA
      negative samples.
AB  - BACKGROUND: An antinuclear antibody (ANA) substrate transfected with the cDNA to
      hyperexpress the 60 kD SS-A/Ro antigen (HEp-2000) has been shown to detect anti
      SS-A/Ro antibodies missed by standard HEp-2 and other immunoassays. Despite this
      evidence, many laboratories remain convinced that with experienced technicians,
      standard HEp-2 is acceptable for ANA detection. AIM: To challenge the ability of
      HEp-2000 to detect anti-SS-A/Ro antibodies in samples previously determined to be
      ANA negative using standard HEp-2. METHODS: Three hundred and seventy-one pre
      screened "negative" ANA samples were provided by a university hospital laboratory
      in Germany. These samples were tested on the HEp-2000 substrate at a dilution of
      1:40 by indirect immunofluorescence (IIF). Samples that screened positive for a
      nuclear pattern were titered (range of 1:40-1:640) and all ANA-positive patterns
      were identified. Samples containing at least one positive ANA pattern at a
      dilution greater than or equal to 1:160 were further tested. Samples that
      produced a speckled pattern were tested for antibodies to the extractable nuclear
      antigens (ENA) and samples that showed homogeneous staining were tested for
      antibodies to dsDNA, and if negative, were then tested for anti-histone
      antibodies. RESULTS: Ninety-one patient samples were positive with titers > or
      =1:160. Speckled patterns were the most common finding (30 samples) followed by
      speckled/homogeneous mixed patterns (19 samples) and samples demonstrating the SS
      A/Ro pattern (16 samples) either alone or in combination with other ANA patterns.
      The remaining 26 positive samples consisted of various other ANA patterns. The
      most commonly identified ENAs were SS-A/Ro (14 samples), Scl-70 (11 samples) and
      SSB (6 samples). No antibodies to dsDNA were identified in 23 positive samples
      with homogeneous staining patterns, though 17 of these samples tested positive
      for antibodies to histone. CONCLUSIONS: HEp-2000 detected anti-SS-A/Ro antibodies
      in 16 (4%) of the "ANA negative" samples. In addition to improved sensitivity for
      anti-SS-A antibodies, HEp-2000 demonstrated improved sensitivity over standard
      HEp-2 substrate for other significant ANAs including anti-Scl-70, anti-histone,
      and anti-SS-B antibodies.

PMID- 16285475
TI  - Measurement of whole blood viscosity profiles via an automated viscometer:
      technical details and clinical relevance.
AB  - Recent basic science and large-scale clinical studies involving blood rheological
      factors have led to a similar conclusion: the mechanics of blood flow play an
      important role in the development and progression of various cardiovascular
      diseases (e.g., coronary artery disease, stroke). Several viscometer systems to
      measure whole blood viscosity have been developed, yet blood viscosity
      measurements are not routinely employed in clinical practice, primarily due to
      the complexity of currently available methods. Herein we provide a description of
      a new, computer-controlled capillary viscometer that offers a convenient approach
      to the measurement of blood viscosity over a wide range of shear rates. The new
      viscometer uses a disposable test section, requires small volumes of blood,
      provides viscosity data that compare well with those from other viscometers, and
      completes all testing and data analysis within five minutes.

PMID- 16285476
TI  - Circulating endothelial cells: markers of vascular dysfunction.
AB  - Circulating endothelial cells (CEC) have evolved as a novel method of assessing
      endothelial function. Rarely found in the peripheral blood of healthy
      individuals, CECs increase in a wide variety of conditions such as cardiovascular
      disease, cancer, infection and inflammatory states. Unlike immature endothelial
      progenitor cells (EPC), which are bone marrow derived, CECs are felt to represent
      the detachment of mature endothelial cells from the endothelial monolayer, as a
      result of endothelial insult. In this article we present an overview of CECs and
      their association with a broad spectrum of disease processes.

PMID- 16285478
TI  - Some practical thoughts on restructuring the current guideline of the Federal
      Medical Council (Richtlinie der Bundesarztekammer [RiliBAK]) in Germany for
      quality control of clinical laboratory analyses based on results from external
      quality assessment surveys.
AB  - The present article presents a critical review of the current guidelines of the
      Federal Medical Council (Richtlinie der Bundesarztekammer--[RiliBAK]) in Germany,
      both for internal and external quality control. Examples have been chosen for
      analytes which present problems. These include thyrotropin (TSH) and human
      chorionic gonadotropin (hCG). Data are presented for the difference in analyte
      concentrations found between methods/kits and longitudinally for external quality
      assessment (EQA-) surveys for analytes using reference method values as target
      values. These include: calcium, aspartate aminotransferase (ASAT; GOT),
      aldosterone, cortisol, 17beta-oestradiol and total thyroxine (TT4). Furthermore,
      internal data from participating laboratories concerning laboratory internal
      precision and accuracy have been analysed to show the state of the art with
      regard to both parameters. Data analysis shows the need for a reintroduction of
      concentration-dependent assessment of performance (crossover system) for certain
      analytes, where clinically relevant concentrations are measured at the extremes
      of the calibration curve. The current guideline is at present being restructured
      and should include considerations made in this review of the state-of-the-art of
      clinical laboratory analysis.

PMID- 16285477
TI  - Hemochromatosis gene HFE Cys282Tyr mutation analysis in a cohort of Northeast
      German hospitalized patients supports assumption of a North to South allele
      frequency gradient throughout Germany.
AB  - Hereditary hemochromatosis is the most common autosomal recessive disease in
      populations of Northern European ancestry. Population studies demonstrated highly
      variable frequencies of the HFE Cys282Tyr allele in various regions throughout
      Europe and decreasing allele frequencies from north to south. However, most of
      the German prevalence studies covered the central and southern regions of the
      country. The present study recruited 709 consecutive patients at the time of
      their admission to a Northeast German University Hospital Medical Department.
      Polymerase chain reaction-based assays were used to detect HFE Cys282Tyr and
      His63Asp alleles. Biochemical profiling consisting of transferrin saturation
      rate, and concentrations of ferritin, transferrin, and iron were performed in
      Cys282Tyr homozygotes and Cys282Tyr/His63Asp heterozygotes, respectively. Results
      were compared with previous German prevalence studies. Analysis of 709 Caucasian
      patients resulted in 650 (91.7%) homozygous HFE wild-type carriers, 55 (7.74%)
      Cys282Tyr heterozygotes, 4 (0.56%) Cys282Tyr homozygotes and 6 (0.85%)
      Cys282Tyr/His63Asp compound heterozygotes. The HFE Cys282Tyr allele frequency was
      4.44%. Phenotypic markers of iron overload were elevated in one homozygote. We
      conclude that in contrast to previous hemochromatosis prevalence studies in
      Germany using blood donors or employees, the present study involving hospital
      patients estimated a HFE Cys282Tyr allele frequency of 4.44% and supports the
      emerging concept of an allele gradient decreasing from North to South within
      Germany.

PMID- 16285479
TI  - [Morphological classification is not keeping up with the times ].

PMID- 16285480
TI  - [Therapeutic application of TNF-alpha inhibitors infliximab and etanercept in
      inflammatory skin disorders].
AB  - BACKGROUND: The treatment of inflammatory skin diseases is at present often
      empirical as causal therapeutic approaches are not available because of
      incomplete knowledge of the immune pathogenesis. The current therapeutic
      approaches can induce remission, but often produce undesirable side effects. On
      the basis of experience gained in cytokine modulation therapy of chronic
      inflammatory diseases such as rheumatoid arthritis and psoriasis, the use of TNF
      alpha inhibitors could represent a further, more specific and effective
      therapeutic option for other selected inflammatory skin diseases. PATIENTS AND
      METHODS: The current status of the therapeutic effect of anti-TNF-alpha blockers
      is discussed based on our own observations and a review of the current
      literature. Potential undesirable side effects and possible contraindications for
      this therapy are also considered. RESULTS AND CONCLUSIONS: Based on the recent
      findings, the use of TNF-alpha blockers seems to be promising in the treatment of
      therapy-resistant inflammatory dermatoses. At present, guidelines for indications
      and contraindications for anti-TNF-alpha treatment of inflammatory skin disorders
      do not exist. Such guidelines are necessary to improve the efficacy of
      anticytokine treatment and to reduce side effects.

PMID- 16285481
TI  - [Clinical aspects and pathogenesis of UV-induced pigmentary disorders].
AB  - Solar and ultraviolet (UV) radiation, respectively, are the strongest stimuli for
      the induction of pigmentation in human skin. UV radiation induces pigmentation by
      exerting direct and indirect effects on melanocytes. Melanogenesis is a very
      complex process whose molecular mechanisms are not yet completely understood.
      Acute UV exposure induces the non-protective immediate pigment darkening as well
      as delayed tanning which exerts photoprotective effects. Chronic UV exposure
      causes permanent pigmentary changes by inducing solar lentigines and pigmented
      actinic keratoses as well hypopigmentated areas. Artificial UV irradiation (UVA,
      PUVA) can also induce pigmentary disorders, including lentigines. Since the
      therapeutic options for UV-induced pigmentary changes are limited consequent
      protection as a prophylactic measure is recommended.

PMID- 16285482
TI  - [Occupational allergy to mugwort].
AB  - BACKGROUND: Mugwort (Artemisia vulgaris) has traditionally been used as a spice,
      vegetable and as a herbal medicine. The main representatives of the Artemisia
      family besides Artemisia vulgaris include Artemisia absinthum and Artemisia
      dracunculus (estragon). Mugwort pollen allergens are important in triggering late
      summer and fall pollinosis; in addition cross reactivity occurs between Artemisia
      vulgaris pollen allergens and celery, carrottes and certain spices belonging to
      the family of Umbelliferae. PATIENTS: A florist with a pre-existing sunflower
      allergy developed a life-threatening glottal edema after occupational contact
      with mugwort. She did not suffer from an oral allergy syndrome towards mugwort
      pollen cross allergens. RESULTS: Skin testing (prick and scratch testing)
      revealed a strong sensitisation against mugwort and estragon. Specific IgE
      antibodies against mugwort, sunflower, carrots, celery, fennel and anis were
      elevated in the peripheral blood. CONCLUSIONS: The observation of a severe
      mugwort allergy with life-threatening complications in a florist underscores the
      high allergenic potential of Artemisia vulgaris and documents for the first time
      the occupational significance of this allergy.

PMID- 16285483
TI  - [Clinical value of a dermatoscopic classification of Clark nevi].
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the practical
      value of the dermatoscopic classification of Clark nevi PATIENTS AND METHODS:
      Dermatoscopic images of 268 lesions clinically and dermatoscopically diagnosed as
      Clark nevi were presented to 2 dermatologists without knowledge of the
      histological diagnosis. The dermatologists evaluated the lesions according to a
      simplified version of the classification scheme for Clark nevi proposed by
      Hofmann-Wellenhof and differentiated between 12 different types of Clark nevi.
      RESULTS: The most common type of Clark nevus was the reticular-homogenous type (n
      = 64, 23.9%), followed by the globular-homogeneous type (n = 32, 12%) and by the
      homogenous type (n = 30, 11.2%). The overall inter-rater agreement between the
      examiners was moderate to good (kappa = 0.58). The highest level of agreement was
      found for the peripheral hyperpigmented type (kappa = 0.83). Histologically, 17
      lesions (6.3%) were diagnosed as melanomas. The frequency of melanoma was highest
      among the peripheral-hyperpigmented type for one observer and among the
      homogenous type for the other observer. No melanoma was found among the globular,
      reticular-globular, and the central-hyperpigmented types. CONCLUSIONS: A
      dermatoscopic classification of Clark nevi is practically feasible and allows--to
      some extent--a risk stratification of Clark nevi, which could be useful for
      clinical management.

PMID- 16285484
TI  - [Subcutaneous fat necrosis of the newborn].
AB  - Subcutaneous fat necrosis presents as red-to-bluish, indolent, well
      circumscribed, subcutaneous nodules and plaques, unusually in healthy infants.
      Histologically, a lobular panniculitis with a mixed inflammatory infiltrate is
      seen. Characteristic crystalloid structures can be found within some of the
      lipocytes and, most prominently, within macrophages. This rarely diagnosed skin
      disease is harmless and self-limited, yet the associated hypercalcaemia has a
      high complication rate.

PMID- 16285485
TI  - [Allergic contact eczema from shellac and 1,3-butylene glycol in an eyeliner].
AB  - BACKGROUND: The diagnostic approach to eyelid eczema is often a great problem in
      daily practice. PATIENT AND METHOD: A 16-year old girl developed recurrent severe
      pruritic edema of the eyelids, followed by redness and scaling. Various cosmetics
      particularly an eyeliner were considered as possible causes. Patch testing was
      performed with the standard series, some supplemental series and all ingredients
      of the eyeliner. RESULTS: The eyeliner produced a papular reaction after 2 days
      of open application, confirming a high degree of contact sensitization. The
      patient reacted with a 3+ reaction to the ingredients shellac (20% in ethanol)
      and 1,3-butylene glycol (2% in water). All remaining materials failed to produce
      a reaction. CONCLUSIONS: Careful allergologic investigations are necessary in
      cases of edema and/or eczema of the eyelids; the cosmetics used by the patients
      are of utmost importance. The causative allergen may not be present in the usual
      patch test series and can only be identified by testing all ingredients. Shellac
      is now widely used in cosmetics and is increasingly identified as a contact
      allergen in eye make up.

PMID- 16285486
TI  - [An unusual case of pyoderma gangrenosum with necrotizing granulomatous
      dermatitis].
AB  - Four distinctive clinical and histological variants of pyoderma gangrenosum have
      been proposed: (1) ulcerative, (2) pustular, (3) bullous, and (4) vegetative. The
      rate of progression and associated systemic diseases, as well as the
      histopathologic changes, can vary considerably between these clinical variants. A
      64-year-old man presented with ulcerative pyoderma gangrenosum associated with
      renal cell carcinoma and IgA paraproteinemia; he responded to oral thalidomide.
      Histopathology revealed unusual findings with signs of leukocytoclastic
      vasculitis, basophilic degeneration of collagen and zones of suppuration with a
      palisaded histiocytic and epithelioid granulomatous infiltration throughout the
      dermis.

PMID- 16285487
TI  - [Skin diseases in thyroid gland diseases].

PMID- 16285488
TI  - [Linear symptomless skin atrophy in a 14-year old girl].

PMID- 16285489
TI  - [Cryotherapy in dermatology].

PMID- 16285490
TI  - [42nd DDG Congress, 6-10 May in Berlin: top-level dermatology on a wider basis].

PMID- 16285491
TI  - [A pleading for the DDA].

PMID- 16285492
TI  - [Histological diagnosis of onychomycosis].
AB  - It is mandatory to establish a firm diagnosis before starting systemic
      antimycotic therapy because of potential side effects and relatively high therapy
      costs. Direct microscopy and fungal culture are the most widely employed
      diagnostic tools. Not infrequently, a strong clinical suspicion cannot be proven
      by even repeated direct microscopic examinations and fungal cultures. In these
      cases histologic examination is a simple alternative. We identified 32 cases of
      histopathologically proven onychomycosis; of the 29 where a fungal culture was
      performed, only 14 (48%) were positive. Direct microscopy was performed only in
      12 cases since most had repeatedly negative direct microscopy results before
      being referred to us; 5 cases (42%) were positive. Histopathology for
      onychomycosis has several advantages in addition to its sensitivity--particularly
      in difficult to diagnose cases: lack of the danger of contamination, a permanent
      preparation with the possibility to demonstrate fungal invasion of the nail organ
      and to identify other or concomitant nail disorders, simplicity of the procedure;
      quicker results as compared to fungal culture. Exact specification of the fungus
      is not possible with histology. Even though histological examination is not
      mentioned in the current guidelines for onychomycosis of the German
      Dermatological Society, it should be kept in mind as a simple but sensitive
      diagnostic tool.

PMID- 16285493
TI  - [The use of high dose intravenous immunoglobulins in dermatology].
AB  - High dose intravenous immunoglobulins (IVIG) are important agents in the
      treatment of numerous diseases in rheumatology and dermatology. Because the
      diseases treated with IVIG are rare, their use is mostly not based on controlled
      randomized trials. Since the high costs of therapy often prohibit the use of IVIG
      as first line therapy and as there are no guidelines on the use of IVIG in
      dermatologic diseases, a consensus conference was held in Wiesbaden, Germany, to
      address these issues. This manuscript documents the expert consensus on the use
      of IVIG in dermatology and reflects current clinical practice. It should be a
      guideline for the practitioner for the use of IVIG in dermatologic diseases.

PMID- 16285494
TI  - [Xeroderma pigmentosum: children of the moon].
AB  - Xeroderma pigmentosum is based on a genetic defect in the DNA repair system,
      which is diagnosed in early childhood. Xeroderma pigmentosum is a rare disorder,
      which is transmitted in an autosomal recessive manner. Children with xeroderma
      pigmentosum display hypersensitivity to ultraviolet (UV) radiation. These
      patients experience serious sunburns with minimal exposure and then develop
      poikiloderma in the sun-exposed areas. Squamous cell carcinomas, basal cell
      carcinomas and malignant melanomas all appear during childhood. The majority of
      patients do not reach adult, but die from metastatic cutaneous malignancies.
      Genetically, xeroderma pigmentosum is differentiated into 7 complementation
      groups (XP-A to XP-G) and the xeroderma pigmentosum variants (XP-V). The
      assignment to the specific complementation group is made by fusing of xeroderma
      pigmentosum fibroblasts. Xeroderma pigmentosum must be distinguished from other
      so-called DNA repair deficiency syndromes, including Cockayne syndrome and
      trichothiodystrophy. A topical DNA repair enzyme appears to be helpful. A
      recombinant liposomal encapsulated T4 endonuclease V repairs UV-induced
      cyclobutane-pyrimidine dimers. Direct curative treatment of xeroderma pigmentosum
      could be achieved with gene therapy in future. Transfection of an intact repair
      gene which specifically codes for the missing repair protein could open new
      possibilities in the therapy of xeroderma pigmentosum.

PMID- 16285495
TI  - Impaired skin barrier and atopic diathesis in perioral dermatitis.
AB  - BACKGROUND: Perioral dermatitis (PD) is a common dermatological disease whose
      aetiology and pathogenesis remain speculative. We investigated skin barrier
      function and various markers of the atopic diathesis to elucidate their impact on
      the development of perioral dermatitis. PATIENTS AND METHODS: Forty patients (24
      to 69 years of age) with PD were evaluated. Transepidermal water loss was
      measured in three regions of the face (lateral chin, perinasal cheek and side of
      the nose) and the patients were assessed for clinical criteria for atopy. Prick
      tests were performed, and specific IgE against a mixture of aeroallergens (CAP
      SX1) was measured. The control group consisted of 62 individuals (20 to 68 years
      of age) without a history of PD or active disease. RESULTS: Transepidermal water
      loss was significantly increased (P < 0.001) on all regions of the face in the
      patient over the control group. Significantly (P < 0.001) higher values were also
      found for the patient group regarding history (52.5% vs. 17.7%) and clinical
      signs of atopic diathesis (> or = 4 features: 72.5% vs. 0%), prick test
      reactivity (> or = 2 reactive prick tests: 60% vs. 12.9%), and specific IgE
      against aeroallergens (CAP SX1 classes > or = 2: 60.0% vs. 17.7%). CONCLUSIONS:
      Our findings emphasize the relevance of impaired skin barrier function as a
      pathogenic factor in the causation of perioral dermatitis. The susceptibility of
      atopic skin to irritants increases as soon as the skin becomes eczematous.
      Therefore, we propose that atopic diathesis serves as an intensifier, supporting
      development and continued presence of perioral dermatitis after nonspecific
      irritant mechanisms have induced impaired skin barrier function.

PMID- 16285497
TI  - [Vancomycin-induced linear IgA dermatosis].
AB  - Linear IgA disease is a rare autoimmune bullous skin disorder that may be
      idiopathic or drug-induced. The mechanisms of loss of self-tolerance to target
      antigens of the dermo-epidermal junction are unclear and may be variable.
      Regardless of the etiology, the clinical presentation is quite heterogeneous.
      Frozen sections of a blister roof are helpful in early diagnosis to rule out full
      thickness epidermal necrosis or subcorneal separation as seen in toxic epidermal
      necrosis or staphylococcal scaled skin syndrome, respectively. Drug-induced cases
      of linear IgA disease typically resolve quickly once the causative agent is
      withdrawn. Vancomycin is the best-documented insiting drug in the literature. The
      significance of further associations such as malignancy or different autoimmune
      diseases is uncertain. Review of medication exposures after diagnosis is crucial
      in identifying possible offending agents. We present a patient with vancomycin
      induced linear IgA disease in whom the drug was immediately discontinued because
      of the characteristic clinical presentation and rapid histopathological
      examination. The development of new blisters stopped within 24 hours and the skin
      healed within 2 weeks.

PMID- 16285496
TI  - [Cryosurgery--the last resort or a surgical alternative in the treatment of
      lichen sclerosus et atrophicus of the vulva (LSAV)?].
AB  - BACKGROUND: The treatment of LSAV consists mainly of topical corticosteroids,
      progesterone or testosterone. Often these approaches neither improve the clinical
      findings nor relieve the symptoms. We evaluated cryotherapy as a possible
      therapeutic option. PATIENTS AND METHODS: Nine girls (age between 5 and 15 years,
      mean 9 years) and 22 women (age between 33 to 74 years, mean 54 years) with
      clinically and histologically confirmed LSAV were treated with cryotherapy.
      RESULTS: All patients experienced improvement of their clinical signs and
      symptoms. Five patients had a second cycle of cryotherapy after an average of
      10,6 months; 2 women were treated a third time. CONCLUSIONS: Cryotherapy is an
      effective therapeutic option for LSAV. It has few side effects and seems to be an
      attractive alternative especially in children.

PMID- 16285498
TI  - [Atypical erythema gyratum repens secondary to bronchogenic carcinoma].
AB  - Erythema gyratum repens (EGR) is an obligate paraneoplastic eruption that
      indicates an underlying malignancy, most commonly cancer of the lung or breast.
      The characteristic clinical finding is a rapidly expanding, mildly scaling
      dermatosis with a 'wood-grain' pattern. This typical concentric erythema is not
      seen in all patients. Other findings may include pruritus, palmoplantar
      keratoderma and/or blood eosinophilia. We report a case of EGR where the
      diagnosis was suggested less by the wood-grain pattern than by the dynamics of
      the lesions.

PMID- 16285499
TI  - [Facial foreign body granulomas after dermal injection of a polylactate-based
      implant for wrinkles].
AB  - New methods are constantly introduced for soft tissue augmentation to correction
      of scars and wrinkles. Each method has its advantages and disadvantages. A 48
      year old woman developed visible and palpable plaques and papules after treatment
      of the nasolabial and glabella folds with a poly L-lactic acid implant.
      Histological examination revealed a foreign body granuloma, while electron
      microscopy showed remnants of the implant material, demonstrating that poly L
      lactic acid can also induce a foreign body reaction.

PMID- 16285500
TI  - [Skin aging--clinical aspects and pathogenesis].

PMID- 16285501
TI  - [A 72 year-old man with chronic inflammable swelling of the left wrist joint].

PMID- 16285502
TI  - [Dermatologic in-patient rehabilitation of atopic dermatitis in adulthood].

PMID- 16285503
TI  - [Trichoteiromania: rubbing or scratching].

PMID- 16285504
TI  - [Enhancement of immune responses to hepatitis B DNA vaccine by superantigen SEA
      in mice].
AB  - To investigate the adjuvant effect of plasmid DNA encoding superantigen SEA
      (D227A) (pmSEA) on immune responses induced by HBV DNA vaccine containing HBV
      preS2 and S antigen in BABL/c (H-2d). BALB/c mice were immunized intramuscular
      injection with HBV DNA vaccine (pHBVS2S) mixed with or without pmSEA plasmid.
      Antibodies againat HBV PreS2 and S antigen in the sera were accessed by Anti-HBs
      ELISA, and the HBsAg specific cytotoxic T lymphocytes (CTLs) activity was
      determined by 5 Chromium Release Assay. The HBs peptide-specific IFN-gamma
      secreting T cells were detected by ELISPOT. Anti-HBs antibody titers and CTLs
      activity in mice immunized with pmSEA + pHBVS2S group were significant higher (P
      < 0.05) than pHBVS2S DNA vaccine group. The ratio of IgG1/IgG2a (0.282) was
      apparently different from the group immunized with peptide (10). Mice immunized
      with HBV DNA vaccine plus adjuvant produce higher titer of IgG1 and IgG2a
      antibodies against HBV S antigen 1.36 and 1.73 time higher than that without
      adjuvant respectively. HBs peptide--specific IFN-gamma secreting T cells
      increased 2 - 3 times by the pmSEA adjuvant, compared to DNA vaccine group. HBV
      DNA vaccine (pHBVS2S) induces humoral and cellular immuno-responses in BALB/c
      mice, and the responses could be significantly boasted by the plasmid encoding
      mSEA. Therefore the pmSEA was a potential adjuvant for DNA vaccines.

PMID- 16285505
TI  - [Construction and expression of single chain variable fragments (ScFv) against
      human CD19 antigen].
AB  - The genes encoding for the light and heavy chain variable regions were cloned by
      RT-PCR from a murine monoclonal hybridoma cell line, which could produce
      monoclonal antibody to recognize CD19 antigen on human B lymphocyte. Then fused
      the light and heavy chain variable regions together by a short peptide linker
      containing 15 amino acid (Gly4Ser)3 using splice-overlap extensive PCR. The
      recombinant anti-CD19- ScFv was subcloned into the expression vector pET28a and
      induced to be expressed by IPTG in E. coli BL21. SDS-PAGE and Western blot
      analysis showed that the recombinant anti-CD19-ScFv gene was expressed in E. coli
      BL21. ScFv expression was in the form of an inclusion bodies and the purified
      fusion protein was obtained after a series of purification steps including cell
      break, inclusion body solubilization, Ni2+ metal affinity chromatography and
      protein refolding. Flow cytometry analysis showed that the ScFv can react with
      human CD19 antigen. In conclusion, recombinant anti-CD19-ScFv gene has been
      successful constructed and expressed in E. coli BL21, which could provide a basic
      study for the future target therapy to the B lymphoid leukemia and B lymphoma.

PMID- 16285506
TI  - [Expression and renaturation of a novel human single-chain Fv antibody against
      SARS-CoV].
AB  - A novel human ScFv H12 against SARS-CoV has been selected from a SARS immune
      library. In order to produce a large amount of ScFv H12, pET28a-H12 expression
      vector was constructed and ScFv H12 was expressed at yield about 30% of total
      proteins in E. coli . Here two different refolding procedures were used to refold
      ScFv H12 from inclusion body: gel filtration chromatography and dilution. The
      results showed that ScFv H12 could be efficiently refolded by both procedures.
      However, the refolding via gel filtration was 1.5 time more effective than that
      of dilution. The affinity of ScFv H12 to SARS-CoV virion was detected as Kd =
      73.5 nmol/mL.

PMID- 16285507
TI  - Homodimerization of the c-Abl protein tyrosine kinase.
AB  - The c-Abl nonreceptor tyrosine kinase is activated in the cellular responses to
      genotoxic, oxidative and other forms of stress. Using tagged forms of c-Abl, the
      present studies demonstrate that c-Abl forms homodimers in cells. The results
      show that the c-Abl N-terminal regions interact with the corresponding C-terminal
      regions of both partners in the dimmer. Specifically, the c-Abl SH3 domain binds
      to a proline-rich motif at amino acids 958-982 in the c-Abl C-terminal region.
      Deletion of the proline-rich motif disrupts dimmer formation. These findings
      provide the first evidence that c-Abl forms homodimers and indicate that
      homodimerization can contribute to the regulation of c-Abl activity.

PMID- 16285508
TI  - [Cloning and expression of the extracellular domain of 4-1BBL].
AB  - RT-PCR was used to clone DNA fragment of the extracellular domain of 4-1BBL from
      human THP-1 cells (human monocyte), and the expression vector pAYZ4-1BBL was
      constructed by cloning the extracellular domain of 4-1BBL into the expression
      vector pAYZ. The extracellular domain of 4-1BBL was expressed in E. coli 16C9 and
      purified by affinity chromatography. SDS-PAGE and Western blot analysis showed
      that the relativae molecular weight of soluble 4-1BBL is 22kD which was
      consistent with the theoretically predicted value. So far as we know, it is the
      first time that the soluble expression of 4-1BBL in E. coli was achieved 4-1BBL
      induced a significant release of IL-2 in stimulated Jurkat cells after 48h
      incubation, especially in the presence of tumor cell. At the same time the
      apoptosis level of Jurkat cell reduce more than 50%. In conclusion, 4-1BBL may be
      useful in cancer immunotherapy.

PMID- 16285509
TI  - [The purification of HBV full-length PreS protein in Pichia pastoris].
AB  - The Pichia pastoris strain GS115-PreS could produce a high expression level of
      full-length PreS protein that secreted to the supernatant after methanol
      induction in the fermentation. The Western blot analysis showed a single band
      with expected molecular mass of 48kD and that the major component of the
      particles was the full-length PreS protein (PreS1 + PreS2 + S) and small envelope
      protein (S) of 48 and 28 kD, respectively. Electron microscopy image showed PreS
      particles with 30 nm in diameter. The supernatants of the fermentation were
      desalted and concentrated. Purified PreS protein was obtained by DEAE-SFF anion
      exchange column chromatography and the PreS particles were obtained by
      ultracentrifugation and sucrose density gradient. The ELISA assay results proved
      that both full-length PreS protein and particles showed high immunogenicity and
      specificity. P/N ratio further demonstrated that the immunogenicity of the
      particles is higher than the full-length PreS protein.

PMID- 16285510
TI  - [Construction of DNA and RNA based on bifunctional replicon vector derived from
      Semliki Forest virus].
AB  - DNA-based replicon expression vector pSMCTA and helper vector pSHCTA were
      constructed by replacing the SP6 promoter used in the original system pSFV1 and
      pSFV-helper2 derived from Semliki Forest virus (SFV) with the RNA polymerase II 
      dependent cytomegalovirus immediate early (CMV IE) enhancer/promoter and T7
      promoter, and inserting BGH transcription termination and polyadenylation signal
      downstream 3'-untranslated region (UTR). The RNA polymerase II -dependent
      cytomegalovirus immediate early (CMV IE) enhancer/promoter and T7 promoter in
      pSMCTA and pSHCTA could drive transcription to produce replicon RNA in vivo and
      ex vivo. High level expression of foreign genes (GFP and LacZ) could be
      demonstrated by transfecting BHK21 cells with the new replicon expression vectors
      based on both DNA and RNA, and recombinant virus particles (RVP) be prepared by
      cotranfecting the expression vectors with the helper vectors. Foreign genes were
      also highly expressed in cells (BHK21) which were infected with RVP activated by
      alpha-chymotrypsin. The bifunctional replicon vectors can be used in highly
      efficient expression of foreign genes and preparation of RVP ex vivo, also in
      development of replicon vaccines and gene therapy vectors in vivo.

PMID- 16285511
TI  - [The expression of recombinant protein of human interleukin-24 and its anti-tumor
      mechanism].
AB  - The hIL24 cDNA sequence was cloned into prokaryotic high expressive vector pET
      21a(+) and recombinant hIL24 was expressed in E. coli with IPTG induction. The
      purified recombinant hIL24 exhibits following functions in HeLa cell: inhibiting
      cell growth, inducing apoptosis, inducing PMBC to secrete IL-6, TNF-alpha, IFN-r
      and inhibiting blood vessel formation. Our preliminary results suggest that the
      apoptosis induced by rhIL24 is through down-regulating expression of anti
      apoptosis factor Bcl-2 and activation of mitochondria apoptosis pathway.

PMID- 16285512
TI  - [Immunogenicity of DNA vaccine expressing GP5 of porcine reproductive and
      respiratory syndrome virus fused with VP22 of bovine herpesvirus 1].
AB  - To enhance the immuogenicity of DNA vaccines expressing the GP5 protein of
      Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), the tegument protein
      VP22 (encoded by VP22 gene) of Bovine Herpesvirus 1 (BHV-1), which has been
      demonstrated to exhibit the unusual protein transduction property, was fused to N
      terminus of GP5 of DNA vaccine construct pCI-ORF5M, resulting in pCI-VP22-ORF5M
      expressing VP22-GP5 fusion protein. The expression of VP22-GP5 fusion protein was
      confirmed by both indirect immunofluorescence assay (IFA) and Western blot. To
      investigate its immunogenicity, BALB/c mice were immunized with the fusion
      expression plasmid pCI-VP22-ORF5M and non-fusion expression plasmid pCI-ORF5M,
      respectively. The GP5-specific ELISA antibodies, neutralizing antibodies and
      lymphocyte proliferative responses were evaluated at various time points after
      primary immunization. The results showed that GP5-specific ELISA antibodies,
      neutralizing antibodies, and lymphocyte proliferative responses induced by DNA
      vaccine pCI-VP22-ORF5M were higher significantly than those of DNA vaccine pCI
      ORF5M, indicating that fusion expression with BHV-1 VP22 significantly enhances
      the immuogenicity of DNA vaccine expressing the PRRSV GP5 protein, and that this
      strategy may also be useful to develop more efficient DNA vaccines against other
      pathogens.

PMID- 16285513
TI  - [Secreted expression of porcine interferon-gamma gene in Pichia pastoris].
AB  - The porcine interferon-gamma (PoIFN-gamma) gene, in which the sequence encoding
      signal peptide was replaced by that of the alpha-factor of Saccharomyces
      cerevisiae, was cloned into Pichia pastoris expression vector pPIC9K. The
      recombinant plasmid pPIC9K-alpha-PoIFN-gamma was then transformed into Pichia
      pastoris GS115 cells by electroporation and stable multicopy recombinant Pichia
      pastoris strains were selected by G418 resistance. Two recombinants of multiple
      inserts were obtained. SDS-PAGE and Western blot assays of culture broth from a
      methanol-induced expression strain demonstrated that recombinant PoIFN-gamma,
      17kD and 23kD proteins, were secreted into the culture medium. Target proteins,
      60% of total proteins, were obtained in the culture medium at the concentration
      of 108 mg/L. This is the first secreted expression of porcine interferon-gamma
      gene in Pichia pastoris.

PMID- 16285514
TI  - [Sequence analysis of alpha-amylase inhibitors genes with resistance to insects
      in wheat and Aegilops].
AB  - The alpha-amylase inhibitors have been proposed as possibly important weapons
      against pests. Thus, it is of importance to identify the specificity of them.
      Based on the EST data of alpha-amylase inhibitor genes that were retrieved from
      NCBI, BBSRC and GrainGenes, two PCR primers were designed. The coding sequences
      of 24 kD dimeric alpha-amylase inhibitors with resistance to insects in 17 wheat
      and Aegilops accessions were investigated and 17 new genes were obtained. Only
      one 24 kD alpha-amylase inhibitor gene was found in each diploid wheat and
      Aegilops accession, whereas 8 genes were characterized from one hexaploid wheat
      variety, indicating that the 24 kD alpha-amylase inhibitors in hexaploid wheat
      were encoded by multi-gene. The deduced amino acid sequences of 2 genes from
      common wheat and 1 gene from Ae. tauschii were the same as the sequence of the
      inhibitor 0.19, and the deduced amino acid sequence of another gene from common
      wheat was similar to the inhibitor 0.53 with only one amino acid difference. The
      amino acid sequences of 24 kD dimeric alpha-amylase inhibitors shared very high
      coherence (91.2%). These results suggest that the alpha-amylase inhibitors in 24
      kD family were derived from common ancestral genes by phylogenesis.

PMID- 16285515
TI  - [Construction of novel recombinant Escherichia coli capable of producing 1,3
      propanediol].
AB  - The 1,3-propanediol oxidoreductase isoenzyme encoding gene (yqhD) from E. coli
      was amplified by PCR. yqhD was inserted in pEtac to yield the recombinant
      expression vector pEtac-yqhD. Over-expression of yqhD in E. coli JM109 was
      achieved with pEtac-yqhD. SDS-PAGE analysis showed an over-expressed recombinant
      product at about 43 kD, consistent with the molecular weight predicted from gene
      sequence. Compared with E. coli JM109 (pEtac), the 1,3-propanediol oxidoreductase
      isoenzyme activity of the recombinant E. coli (pEtac-yqhD) reached 120 u/mg
      protein under the induction of 1.0 mmol/L IPTG at 37 degrees C for 4 hours; at
      similar conditions, enzyme activity of E. coli JM109 (pEtac) was only 0.5 u/mg
      protein. The recombinant E. coli JM109 (pUCtac-dhaB, pEtac-yqhD) was constructed.
      After induction with 1.0 mmol/L IPTG, the recombinant strain could transform 50
      g/L glycerol to 38 g/L 1,3-propanediol under aerobic conditions. This work
      demonstrated firstly that the 1,3-propanediol oxidoreductase isoenzyme could show
      high activity under aerobic conditions.

PMID- 16285516
TI  - [Construction of a trans-splicing ribozyme for restoring EGFP truncation
      mutation].
AB  - Special designed group I intron ribozymes can specifically splice objective RNA,
      repair the mutant gene in RNA level. The specificity of ribozyme is determined by
      nucleotides specific internal guide sequence (IGS) introduced to the enzyme. In
      this study, fragment sequence containing Tetrahymena thermophilia intron I of 26S
      rRNA gene was cloned and cis-splicing activity of this ribozyme was confirmed by
      in vitro transcription. For evaluating the trans-splicing activity of this
      ribozyme, a truncated mutant Green Fluorescence Protein (GFP) vector, XYQ5/XYQ10-
      pEGFP-C2, was constructed. This vector deleted the 3' end 564bp fragment of EGFP
      coding sequence, led to the lost the activity of emitting green fluorescence.
      Trans-splicing ribozyme plasmids ptrans-rib-CMV2 for remedy of the truncated
      mutant EGFP was constructed by PCR and molecular cloning techniques. This vector
      utilizing cloned 26S rRNA intron 1 as core enzyme; selecting T-G site at 194bp of
      EGFP coding sequence as splicing receptor, designed an IGS which is inversely
      complement to the 188-193nt of EGFP mRNA; the 195-890bp fragment of EGFP coding
      sequence was ligated to the 3'-end of ribozyme core. The fragment containing
      these components was inserted to a eukayotic expression vector pRC-CMV2. Using
      linearized XYQ5/XYQ10- pEGFP-C2 and ptrans-rib-CMV2 as templates, truncated EGFP
      mRNA and the constructed ribozyme vector were transcribed and mixed to evaluate
      the trans-splicing activity. Analysis of in vitro transcription products mix by
      RT-PCR verified the existence of wild type EGFP mRNA molecule. Co-transfection of
      XYQ5/XYQ10- pEGFP-C2 with ptrans-rib-CMV2 to Hela cells proved this ribozyme
      restored green fluorescence within cell, but the efficiency was low.

PMID- 16285517
TI  - The growth characteristics and ginsenosides isolation of suspension-cultured
      crown gall of Panax quinquefolium.
AB  - The growth characteristics and ginsenosides isolation of the suspension-cultured
      crown gall of Panax quinquefolium were studied. The result showed that the
      maximum biomass of cultures was 18.6 g/L (dry weight) and the content of
      ginsenosides reached its maximum level of 620.4 mg/L on the 27th day. The
      utilization rates of sugar, phosphorus, nitrogen in NH4+ and nitrogen in NO3-
      were 91.8%, 100%, 81% and 97%, respectively. Four compounds were isolated from
      the suspension-cultured crown gall and their structures were elucidated as
      pseudoginsenoside F11 (I), ginsenoside Rd (II), ginsenoside Rb1 (llI) and
      ginsenoside Rb3 (IV).

PMID- 16285518
TI  - [Establishment of a cell model targeted to NFAT signal transduction pathway for
      preliminary screening of FK506-like immunosuppressants].
AB  - To screen NFAT antagonistic drugs and research signal transduction pathway
      related to NFAT. Four recombinant vectors were constructed. Each consists of
      three tandem copies of the human IL-2 distal NFAT-AP1 binding site in the context
      of the minimal IL-2 enhancer, either the sequence from -326 - +46 or the sequence
      from -89 - +46 (containing only the TATA box), driving a luciferase reporter gene
      or a destabilized enhanced green fluorescence protein (d2EGFP) reporter gene,
      respectively. Transient transfection of Jurkat cells was achieved by
      electroporation with 5 - 10 microg of the above plasmid and one pulse at 200V,
      65ms. Plasmid pEFBos-mNFAT1 constitutively expressing murine full length NFAT1
      protein was used for transient cotransfection. The results showed that neither of
      non-stimulation nor PMA or ionomycin stimulation alone could activate the
      reporter gene except PMA plus ionomycin costimulation. Furthermore, overexpressed
      murine NFAT1 augmented the activation of either IL-2 promoter or NFAT-AP1
      enhancer drived reporter gene compared to the endogenous did. However, the
      reporter gene expression was nearly completely inhibited by pretreatment for 1h
      with FK506 at 5 microg/mL and then stimulation for 6-12h with PMA plus ionomycin
      in the presence of FK506. These findings indicated that such a transient Jurkat
      cell model offered a potential platform for preliminary screening of FK506 or CsA
      like immunosuppressive agents.

PMID- 16285519
TI  - [Cryopreservation of mouse embryos in ethylene glycol-based solutions: a search
      for the optimal and simple protocols].
AB  - Although ethylene glycol (EG) has been widely used for embryo cryopreservation in
      domestic animals, few attempts were made to use this molecule to freeze mouse and
      human embryos. In the few studies that used EG for slow-freezing of mouse and
      human embryos, complicated protocols for human embryos were used, and the
      protocols need to be simplified. Besides, freezing mouse morula with EG as a
      cryoprotectant has not been reported. In this paper, we studied the effects of
      embryo stages, EG concentration, duration and procedure of equilibration, sucrose
      supplementation and EG removal after thawing on the development of thawed mouse
      embryos, using the simple freezing and thawing procedures for bovine embryos. The
      blastulation and hatching rates (81.92% +/- 2.24% and 68.56% +/- 2.43%,
      respectively) of the thawed late compact morulae were significantly (P < 0.05)
      higher than those of embryos frozen-thawed at other stages. When mouse late
      compact morulae were frozen with different concentrations of EG, the highest
      rates of blastocyst formation and hatching were obtained with 1.8mol/L EG. The
      blastulation rate was significantly higher when late morulae were equilibrated in
      1.8 mol/L EG for 10 min prior to freezing than when they were equilibrated for 30
      min, and the hatching rate of embryos exposed to EG for 10 min was significantly
      higher than that of embryos exposed for 20 and 30 min. Both rates of blastocyst
      formation and hatching obtained with two-step equilibration were higher (P <
      0.05) than with one-step equilibration in 1.8 mol/L EG. Addition of sucrose to
      the EG-based solution had no beneficial effects. On the contrary, an increased
      sucrose level (0.4 mol/L) in the solution impaired the development of the frozen
      thawed embryos. In contrast, addition of 0.1 mol/L sucrose to the propylene
      glycol (PG)-based solution significantly improved the development of the frozen
      thawed embryos. Elimination of the cryoprotectant after thawing did not improve
      the development of the thawed embryos. The cell numbers were less (P < 0.05) in
      blastocysts developed from the thawed morulae than in the in vivo derived ones.
      In summary, embryo stage, EG concentration, duration and procedure of
      equilibration and sucrose supplementation had marked effects on development of
      the thawed mouse embryos, and a protocol for cryopreservation of mouse embryos is
      recommended in which the late morulae are frozen in 1.8 mol/L EG using the simple
      freezing and thawing procedures of bovine embryos after a two-step equilibration
      and the embryos can be cultured or transferred without EG removal after thawing.

PMID- 16285520
TI  - [Directed evolution of D-lactonohydrolase by error prone PCR and DNA shuffling].
AB  - D-lactonohydrolase is useful in the procedure of resolution of racemic
      pantolactone to produce D-pantolactone, but the activity and stability under low
      pH of the wild type enzyme is not satisfactory enough to be applied to industrial
      production. The expected properties of wild type enzyme were enhanced by directed
      evolution. According to the formation of products and pH indicators, a screening
      system was designed. After three sequential error prone PCR and one round DNA
      shuffling followed by screening, Mut E-861, the best mutant with improved
      activity and stability under low pH situation was obtained. Gene analysis of the
      Mut E-861 mutant indicated that the mutant enzyme had A352C, G721A mutations and
      a silent mutation of position 1038. Moreover, the activity and stability of Mut E
      861 were determined. The results showed that the activity of this mutant was 5.5
      fold higher than that of wild type, and the stability under low pH was improved
      at no expense of D-lactonohydrolase activity. After incubated at pH 6.0 and pH
      5.0 the activity of D-lactonohydrolase could be retained 75% to 50%, however,
      compared with 40% to 20% for wild type.

PMID- 16285521
TI  - [Gene cloning and expression of serine protease SFP2 from Streptomyces fradiae
      var. k11].
AB  - Extracellular serine protease SFP2 from Streptomyces fradiae var. k11 with high
      feather-degrading activity was purified. The partial amino acid sequences of
      internal peptide of purified SFP2 were determined, and the partial gene encoding
      SFP2 was cloned by PCR using the degenerate primers designed according to the
      amino acid sequences. Complete sfp2 gene was cloned by screening the genomic DNA
      library of Streptomyces fradiae var. k11. The Open Reading Frame of sfp2
      including pre- pro-enzyme is 924bp long (EMBL Accession number: AJ784940). The
      signal peptide sequence is as long as 114bp, the precursor sequence is 810bp and
      the mature enzyme is 576bp long, encoding 191 amino acid resides with the
      putative molecular weight of 19.112kD. In E. coli and Bacillus subtilis, the two
      sequences encoding SFP2 pro-enzyme and mature enzyme were both expressed
      successfully. The pro-enzyme expressed had normal biological function and its
      mature product had normal enzymatic activity.

PMID- 16285522
TI  - [Oriented immobilization of papain on metal chelating carriers].
AB  - Based on the technology of protein separation with immobilized metal ion affinity
      chromatography (IMAC), a method for oriented immobilization of papain has been
      selected. Papain was successfully immobilized on magnetic agarose carriers. Cu2+
      with iminodiacetate (IDA) was used as the chelating ligand to be correlated with
      the histidine on papain (His-81). The optimum immobilization conditions of enzyme
      were as flows: Cu2+ 0.15 x 10(-2) mol/g carriers, time was 4h, enzyme load was 30
      mg/g carrier, pH was 7.0, respectively. The pH and temperature were 8.0 and 70
      degrees C for immobilized enzyme. The recovery activity of immobilized enzyme was
      retained 68.4%. The carrier could be recovered from the spent immobilized enzyme,
      to be reused. After 5 times, the reimmobilization of papain on the regenerated
      matrix was 79.71% effective with the retention of maximum enzyme activity. The
      cost of carriers used for industrial applications is very important. The
      regenerability of carriers is therefore, relevant. The mild conditions used for
      immobilization, the high recovery of immobilized preparations, the stability and
      the regenerability of the matrix are the main features of the method reported
      here. All above indicate this method can be applicable and promising in enzyme
      immobilization field.

PMID- 16285523
TI  - [High expression of mirobial transglutaminase gene from Streptoverticillium
      mobaraense in Escherichia coli].
AB  - The microbial transglutamunase (MTG) gene was amplified from the genomic DNA of
      Streptoverticillium mobaraensea by using PCR and inserted into pET vector to
      construct the expression plasmid called pET-MTG. The pET-MTG was transfected into
      E. coli (Rosetta DE3) and the MTG protein was found to be highly expressed as
      inclusion bodies. The inclusion bodies were isolated and subjected to
      denaturation and re-naturation, followed by strong cation ion-exchange
      chromatography to purify the expressed MTG. The specific activity of purified MTG
      was close to that of native MTG. Taken together, this study might provide a base
      for the industrial production of microbial transglutaminase.

PMID- 16285524
TI  - [Kinetics model of spherical immobilized cellulase].
AB  - A kinetics model was developed for predicting and simulating immobilized
      cellulase performance, which follows Michaelis-Menten kinetics with competitive
      product inhibition. Taking into account the effects of competitive product
      inhibition, inner diffusional limitation, substrate concentration and carrier
      size, the substrate distribution and the product distribution in carriers were
      investigated, and the effectiveness factors were also calculated over a wide
      range of parameters. The effects of competitive product inhibition are shown to
      increase the substrate concentration in the carrier, and, additionally, to
      increase the effectiveness factors slightly. With the increase of inner diffusion
      coefficient, both the effectiveness factors and the substrate concentration in
      the carrier increase. As the carrier size increases, on the other hand, these
      values decrease. The effectiveness factors and the substrate concentration in the
      carrier are found to increase when substrate concentration in the reaction system
      increases.

PMID- 16285525
TI  - [Expression of fusion protein of parathyroid hormone and transferrin N-terminal
      half-molecule in Pichia pastoris].
AB  - The fused gene (PTH-TFN) of parathyroid hormone (PTH) gene and transferring N
      terminal half-molecule (TFN) gene was amplified by multiple PCR and inserted into
      pPIC9 vector. The recombinant plasmid pPIC9-PTH-TFN was transformed into Pichia
      pastoris GS115 by PEG. After methanol induction, the target protein was expressed
      in fermentation supernatant at high level. The fused protein PTH-TFN with purity
      being higher than 95% was finally obtained after purification through two-step
      chromatography: SP Sepharose Fast Flow and Phenyl Sepharose Fast Flow. Western
      blot analysis and adenylate cyclase assay proved that the fused protein exhibited
      the bioactivity to stimulate cAMP synthesis and the ability to bind Fe3+ in the
      Fe3+ saturation study as the recombinant TFN did indicating that TFN could be
      used as the transcellar carrier of PTH.

PMID- 16285526
TI  - Protein amino acid composition of plasma membranes affects membrane fluidity and
      thereby ethanol tolerance in a self-flocculating fusant of Schizosaccharomyces
      pombe and Saccharomyces cerevisiae.
AB  - A combination of three amino acids including 1.0 g/L isoleucine, 0.5 g/L
      methionine and 2.0 g/L phenylalanine was found to enhance ethanol tolerance of a
      self-flocculating fusant of Schizosaccharomyces pombe and Saccharomyces
      cerevisiae. When subjected to 20% (V/V) ethanol for 9 h at 30 degrees C, all
      cells died whereas 57% remained viable for the cells grown in the presence of the
      three amino acids. Based on the analysis of protein amino acid composition of
      plasma membranes and the determination of plasma membrane fluidity by measuring
      fluorescence anisotropy using diphenylhexatriene as a probe, it was found that
      the significantly increased ethanol tolerance of cells grown with the three amino
      acids was due to the incorporation of the supplementary amino acids into the
      plasma membranes, thus resulting in enhanced ability of the plasma membranes to
      efficiently counteract the fluidizing effect of ethanol when subjected to ethanol
      stress. This is the first time to report that plasma membrane fluidity can be
      influenced by protein amino acid composition of plasma membranes.

PMID- 16285527
TI  - [Analyses of Streptomyces coelicolor inner membrane proteome by multidimentional
      protein identification technology].
AB  - Streptomyces coelicolor is the model species among streptomycetes. Until now,
      proteomic analyses of S. coelicolor have been conducted using two-dimensional
      polyacrylamide gel electrophoresis and matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry method, few integral membrane
      proteins were identified due to the hydrophobic and low-abundance nature of these
      proteins. In this work, 154 possible inner membrane proteins from S. coelicolor
      were identified using high pH-proteinase K sample preparation method and
      multidimensional protein identification technology, among them 44 are integral
      membrane proteins containing at least one transmembrane domain, most peptides and
      their corresponding proteins were identified experimentally for the first time.

PMID- 16285528
TI  - [Study on energy dissipation in modified airlift bioreactor].
AB  - The effects of operational variables and reactor configurations (e.g. diameter of
      draft tube and the number of static mixers) on energy loss in modified airlift
      bioreactor were investigated at the first time. The results showed that improving
      the structure of draft tube could reduce energy loss in the bioreactor. When the
      diameter of draft tube and the number of static mixers were 4.0cm and 39,
      respectively, the total energy loss in the modified bioreactor was the least
      among all the configurations and 23.6% less than that of the conventional
      counterpart at the same air flowrate. The energy consumption for aeration was the
      smallest (43.9% less than that of the conventional counterpart) when the diameter
      of draft tube and the number of static mixers were 5.5cm and 13, respectively.
      The highest energy dissipation (70% - 80%) occurred in the riser, the bottom zone
      (about 20%) took the second place and the separator (less than 10%) took the
      third place. The energy dissipation in the downcomer was neglectable under the
      conditions in the research. When the energy loss per unit volume was considered,
      bottom zone stood the first place. It was implied that the riser was the most
      important zone to cut down the energy loss of the bioreactor and some attention
      should also be paid to the bottom zone.

PMID- 16285529
TI  - [Expression of ATR-Fc fusion protein in CHO cells].
AB  - ATR-Fc is a fusion protein consisting of extracellular domain of human anthrax
      toxin receptor (ATR) and a fragment (hinge, CH2, and CH3 domains) of the Fc of
      human IgG1. The aim of ATR-Fc expression is to get an antibody-like molecule
      binding to protective antigen (PA), a component of anthrax toxins, this fusion
      protein may compete with cell surface receptor for PA binding, and block the
      transport of lethal factor (LF) and edema factor (EF) into cells, thereby act as
      an antitoxin to prevent and treat anthrax infection. A DNA fragment encoding N
      terminal amino acids 1-227 of ATR and human IgG1 Fc was inserted into the Hind
      III and Not I sites of pcDNA3.1 to generate the eukaryotic vector pcDNA3.1/ATR-Fc
      for expression of ATR-Fc fusion protein. Using lipofectine-mediated gene transfer
      technique, pcDNA3.1/ATR-Fc was transfected into CHO-K1 cells. After selected with
      G418, a recombinant CHO cell line, ATR-Fc-1D5, whose expression level was about
      10 - 15 microg/(10(6) cells x d), was established. The recombinant protein
      expressed by the ATR-Fc-1D5 cells was purified with protein A chromatography. The
      experimental results demonstrated a direct and specific interaction between ATR
      Fc and PA assessed by ELISA.

PMID- 16285530
TI  - [Construction of a recombinant baculovirus transfer vector with two promoters
      expressing the anti-human CD28 chimeric antibody by using TP-PCR method].
AB  - CD28, a cell surface glycoprotein, predominantly expressed on T cells, belongs to
      the Ig superfamily and provides critical co-stimulatory signals. The data which
      have published indicate that the monoclonal antibody against CD28 can decrease
      curative effects when it was applied in vivo for a long time. In order to avoid
      the human-anti-mouse action, anti-CD28 mAb must be humanized before it can be
      used in clinical study. Chimeric antibody, consisting of variable regions of
      mouse antibody and the constant regions of human IgG1, is often chosen by
      designers in generating humanized antibody. In this study, to prepare the anti
      human CD28 chimeric antibody, the genes coding variable regions of anti-CD28 mAb
      and the constant regions of human IgG1 were cloned by PCR method. Then, the
      target genes were assembled by TP-PCR, a novel method developed for fusing genes
      without designing endonuclease sites at the both end of the target genes, and
      inserted into the baculovirus transfer vector pAcUW3 respectively. Thus, the
      recombinant baculovirus transfer vector with two strong promoters, ph and p10 was
      successfully constructed, which can express two different foreign genes at the
      same time. The recombinant vector was identified by the methods of restriction
      digesting, electrophoresis, PCR amplification and further verified by DNA
      sequence analysis. This work will contribute to expressing the chimeric CD28
      antibody in insect cells.

PMID- 16285531
TI  - [The expression of VP19 gene from prawn white spot syndrome virus in silkworm,
      Bombyx mori using host range-expanded HyNPV].
AB  - Prawn white spot syndrome is caused by the pathogen prawn white spot syndrome
      virus (WSSV). VP19 is a vesicle membrane protein of WSSV. HyNPV (Hybrid of AcNPV
      and BmNPV) constructed by the recombination of BmNPV and AcNPV is a new hybrid
      virus having both of their advantages. The recombinant transfer vector
      pBlueBicHisC-vp19 and recombinant baculovirus HyNPV-VP19 were constructed on the
      basis of the successful cloning of VP19. Newly-molted silkworms Bombyx mori of
      fifth instar were inoculated by the recombinant virus. SDS-PAGE and Western
      blotting analysis showed a specific band, about 21kD, which was consistent with
      the expectation suggesting that the WSSV-VP19 gene was successfully expressed in
      silkworm bodies.

PMID- 16285532
TI  - [Effects of docosahexaenoic acid on rat adipocytes proliferation and
      differentiation].
AB  - To investigate effects of docosahexaenoic acid (DHA) on proliferation and
      differentiation of rat adipocytes and to elucidate its potential mechanism, rat's
      primary preadipocytes in vitro were cultured. Treated adipocytes with 0
      micromol/L (control group), 40 micromol/L (lower dose group) and 160 micromol/L
      (higher dose group) DHA. Cell living rations and proliferation were analyzed by
      trypan blue exclusion and MTT assay. The degree of adipogenesis and
      differentiation were measured by Oil Red O staining extraction assay and the
      expression of peroxisome proliferation activated receptor-gamma2 (PPARgamma2)
      mRNA were detected by reverse transcriptase-polymerase chain reaction (RT-PCR).
      It was demonstrated that cells living ration and the optical density (OD) of MTT
      were all decreased, especially treated by 160 micromol/L DHA at 60 (72 hours (P <
      0.05). The OD of Oil Red O staining and the expression of PPARgamma2 mRNA were
      all decreased after treated by 160 micromol/L DHA (P < 0.01). It can be concluded
      that DHA can inhibite proliferation and differentiation of adipocytes in some
      degree. Higher dose of DHA can markedly decrease adipogenesis and prevent
      differentiation of adipocytes, which may be in part associated with its effect on
      decreasing the expression of PPARgamma2 mRNA.

PMID- 16285533
TI  - [Effects of CO2 on high density culture of Chaetoceros mulleri].
AB  - The effect of CO2 and the manner of CO2 offer on the growth rate and maximual
      cell density of ultro-high density culture of Chaetoceros mulleri in the
      photobioreactor were studied in the work. The amount of CO2 offered to the
      culture was controlled by the parameter of pH value in the culture. Furthermore
      the growth kinetics of Chaetoceros muller in the photobioreactor was studied. The
      results showed requirement of CO2 by the cells and the increase of pH in the
      culture were the key limiting factors to the growth, when a high cell
      concentration in the culture was reached. The offer of CO2 could improve the
      statute of CO2, could control the pH in the culture and increase the growth rate
      and maximum cell density. The results from the experiments of CO2 offer manner
      showed different efficiency to growth was resulted from differences of CO2 offer
      manner. The best way is mixing the CO2 and air before the CO2 was offered to the
      culture.

PMID- 16285535
TI  - [Comparison of Galla Chinesis and sodium fluoride on growth and metabolism of
      bacteria in biofilm model].
AB  - OBJECTIVE: To compare the antibacterial effect between sodium fluoride and Galla
      Chinesis in bioflim model. To evaluate the feasibility of application of Gala
      Chinesis in the clinical practice of caries prevention. METHODS: Streptococcus
      mutans, Streptococcus sanguis, Streptococcus salivarius and Actinomyces
      naeslundii had been chosen as the experimental bacteria. In the experiment,
      biofilmn model was constructed, and two agents were added in the media. After a
      period of continuous culture, the number of bacteria adhering on the HA disc was
      examed, the planktonic pH in the flow cell was recorded continuously, and the
      morphology of the biofilmn formed on the HA disc was observed by SEM. RESULTS:
      (1) Galla Chinesis could inhibit the growth of the four oral bacteria in the
      biofilm just as sodium fluoride. (2) Galla Chinesis and sodium fluoride could
      prevent the descent of the planktonic pH in the flow cell, but Galla Chinesis was
      less efficient than sodium fluoride. (3) The biofilms formed after application of
      Galla Chinesis and fluoride, but the bacterial cells had less matrix than those
      applicated with sucrose. CONCLUSION: Galla Chinesis is one kind of effective
      cariostatic natural agents.

PMID- 16285534
TI  - [Study on breeding up high-yield strain of taxol by protoplast mutagensis].
AB  - In order to obtain resistant mutants to nystatin, ultraviolet radiation and LiCl
      were used to mutagenize the protoplasts of taxol-producing fungi NCEU-1, and four
      positive mutants with high yield of taxol were screened out on nystatin flat.
      After further screening experiments on fermentation, a mutant strain--UL04-5
      which was able to produce taxol with high yield and could be stably passed on in
      genetics was eventually found, it's ability to produce taxol was improved from
      314.07 microg/L (strain NCEU-1) to 418.24 microg/L (strain U04-5).

PMID- 16285536
TI  - [Design and application of internal devices for automatic elasticity distraction
      osteogenesis].
AB  - OBJECTIVE: To improve the design of the devices used for autoatic elasticity
      distraction osteogenesis, and to preliminarily testify their feasibility for
      clinical application. METHODS: The internal automatic distraction devices were
      constructed by three parts, including sinusoid shape memory alloy distractor,
      reconstructive plate and mini-plate. The animal model of trifocal bone transport
      reconstruction of canine mandibular mentis was duplicated, in which a 6 cm
      mandibular mentis segment was removed and the transport disc was created by
      osteotomy in both ends of the mandibular defect. The plates were used for
      internal fixation and shape reconstruction of the mandible. They also served as
      transport distraction guidance for the elasticity distractor. RESULTS: The new
      devices could complete bone transport as expected. Regenerated bone segments were
      formed in two months and both sides of the mandibular body were lengthened.
      Because of the narrow angle and obstruction from the thick soft tissues in the
      mentis area, the ultimate symphysis mentalis was not reconstructed. CONCLUSION:
      The design of the internal elasticity distraction devices showed potential
      feasibility for clinical practice. But further studies are still needed for
      better control of the strength and balance of distraction forces.

PMID- 16285537
TI  - [Expression of Runx2/Cbfa1 in the developing pulpo-dentinal complex of postnatal
      mice].
AB  - OBJECTIVE: To study the expression of Runx2/Cbfa1 in the developing dentin and
      differentiating odontoblasts. METHODS: A postnatal mice teeth developing model
      was built histologically. Immunohistochemical technique was adopted to determine
      the expression of Runx2/Cbfa1 in the developing pulpo-dentinal complex in mice.
      RESULTS: Runx2/Cbfa1 was merely present in predentin in the exact and before the
      11th day's postnatal stages. Meanwhile, it was positively located in odontoblasts
      and dental pulp cells in root region, but negatively in coral part after the 11th
      day's stages. CONCLUSION: Runx2/Cbfa1 may play an important role in the deposing
      of tooth dentin and in the differentiating of odontoblasts and pulp cells.

PMID- 16285538
TI  - [Detection of porphyromonas gingivalis in buccal epithelial cells and subgingival
      plaque].
AB  - OBJECTIVE: To detect Porphyromonas gingivalis (P. gingivalis) in buccal
      epithelial cells and subgingival plaque from periodontally healthy subjects and
      patients with chronic periodontitis. METHODS: 40 subjects were included in the
      healthy group and 39 subjects were included in the diseased group in this study.
      Cells and subgingival plaque samples were collected. The extracted DNA was
      amplified with universal primers and P. gingivalis species-specific primer.
      RESULTS: P. gingivalis was detected in 37.5% of subgingival plaque samples and
      32.5% of buccal mucosa samples in the healthy subjects, but 69.23% of subgingival
      plaque samples and 46.15% of buccal mucosa samples in the periodontitis group.
      Highly statistically significant differences were observed between healthy and
      periodontitis groups in the detections of P. gingivalis of subgingival plaque
      samples. CONCLUSION: P. gingivalis may be one of oral flora because it can be
      detected in the healthy population and not lead to destruction of supporting
      structures of the teeth.

PMID- 16285539
TI  - [Activating protein-1 members in response to changes of wall-shear stress in
      osteoblastic cells].
AB  - OBJECTIVE: To observe activating protein-1 (AP- 1) members in response to changes
      of wall-shear stress in osteoblastic cells in vitro. METHODS: Isolated and
      purified osteoblastic cells from the calvaria of newborn SD rats were cultured
      and subcultured. The third generation cells were subjected to wall-shear stress
      of 0.8 Pa, 1.2 Pa, 1.4 Pa and 1.6 Pa separately. Gene expression of the seven AP
      1 members were studied before (0 h) and 10 min, 15 min, 30 min, 60 min after
      treated with wall-shear stress. RESULTS: The expression of FosB, c-Fos, c-Jun,
      JunD and JunB mRNA increased transiently after application of 1.2 Pa wall-shear
      stress in osteoblastic cells compared to 0.8 Pa , 1.4 Pa and 1.6 Pa stress, and
      peaked at 15 min. CONCLUSION: Mechanical environment changes in osteoblastic
      cells induced a dramatic induction of most of the AP-1 members.

PMID- 16285540
TI  - [Effects of expansion fashion and expansion quantity on retention of cement
      expanded composite screw post].
AB  - OBJECTIVE: To study the effects of expansion fashion and expansion quantity on
      retention of cement-expanded composition screw post (CECSP). METHODS: Ninety
      simulated tooth roots made of polymethylmethacrylate were divided into ten
      groups, each fashion induded five groups. The expanded plastic sheath of
      tricuspid valve was made with the special separated valve device and cemented and
      tightened up into root with the screw post at the same time by ZPC. Then the root
      and screw post-core system was tested by the speed of 10 mm/min on the INSTRON
      4302 and the retention force was recorded. RESULTS: It appeared that the
      difference between different expansion fashion and different expansion quantity
      were significantly (P < 0.05). The retention of expansion fashion one was
      significantly greater than those of fashion two. The retention was best when
      expansion quantity was within 10%. CONCLUSION: During clinic operation, we should
      apply definite fashion and control the expansion quantity within 10%, and the
      screw post should tighten up to the bottom of prepared root.

PMID- 16285541
TI  - [Study on the horizontal transmission of oral Streptococcus mutans in children].
AB  - OBJECTIVE: To find out horizontal transmission of oral Streptococcus mutas (S.
      mutans) in nursery children through analyzing the similarity of S. mutans
      genotypes. METHODS: The study group included 24 nursery children between 3 and 4
      years of age. Dental plaque samples were collected with sterile toothpick and
      cultured on MSB plates for 48 h. Individual Streptococcus mutans group colonies
      representative of the colonial morphologies were subcultured on TPY plates. These
      strains were identified to species level biochemically. AP-PCR fingerprinting was
      preformed after identification. S. mutans isolates from different children with
      very similar fingerprinting profiles were examined by chromosomal DNA
      fingerprinting analysis. RESULTS: Streptococcus mutans group were isolated in
      oral cavities of 66.7% children, 58.3% in caries-free and 75.0% in caries
      children. A total of 4' S. mutans isolates from 24 subjects were analyzed by AP
      PCR, and 29 different amplitypes were identifyied, 45.8% carried tw. genotypes.
      There were 2 genotypes of S. mutans isolated repeatedly among 12 nursery
      children. CONCLUSION: The presence of matching genotypes of S. mutans among
      nursery children suggests horizontal transmission.

PMID- 16285542
TI  - [Clinical evaluation of masticatory function of implant supported dentures in
      partially edentulous patients].
AB  - OBJECTIVE: To evaluate the masticatory efficiency of implant supported dentures
      in partially edentulous patients and the patients' satisfaction on masticatory
      function. METHODS: The masticatory efficiency of implant supported dentures of 22
      patients were tested. The questionnaire of the patients' satisfaction about
      masticatory function had also been collected. The correlativity of the
      masticatory efficiency of implant supported dentures and the scores evaluated by
      patients on masticatory function were analyzed. RESULTS: There were no
      differences in masticatory efficiency between implant supported denture and non
      implant supported denture (natural teeth and porcelain-fused-to-metal fixed
      bridges). The patients gave high scores to the satisfaction about masticatory
      function in the questionnaire. But the test results of masticatory efficiency
      were not related with the scores evaluated by patients. CONCLUSION: The implant
      supported denture could meet the requirement of normal masticatory function. The
      patients were satisfactory with the masticatory function of implant supported
      dentures, but the patients' subjective evaluation about masticatory function was
      probably influenced by varied factors.

PMID- 16285543
TI  - [Comparison on the shaping ability of three different instruments in preparing
      curved molar canals].
AB  - OBJECTIVE: To study the changes of root canal curvatures and apical
      transportation index when the curved root canals were prepared by hand-use
      ProTaper, stainless steel K-files or nickel-titanium K-files. METHODS: Forty-five
      extracted molars, with the degree of root canal curvature from twenty to forty,
      were divided into fifteen sections in curvature sequence. After that, three
      canals of each section were randomly distributed to three different
      instrumentation groups. One group of them was prepared by hand-use ProTaper with
      crown-down technique. The other two groups were instrumented by stainless steel
      or nickel titanium K-files with modified step-back technique to working length.
      The standard digital radiographs were taken to record the profiles of root canals
      and the positions of the tips of the instruments. The change of curvature degree
      between pre- and post-instrumentation and the apical transportation indexes (ATI)
      among three groups were analyzed respectively using SAS statistical software.
      RESULTS: The change of curvature degree between pre- and post-instumentation for
      stainless steel K-files group was largest, and the ATI of stainless steel K-files
      group was significantly greater than that for nickel titanium K-files group (P <
      0.05). The canals prepared by hand-use ProTaper was smallest in the change of
      curvature and ATI among the three groups (P < 0.01). CONCLUSION: When preparing
      curved molar canals, hand-use ProTaper with crown down technique can obtain
      better shaping effect and higher efficiency.

PMID- 16285544
TI  - [Effects on the shear bond strength of orthodontic brackets with different
      concentration of fluorided etching fluid].
AB  - OBJECTIVE: This study was to find out the most suitable concentration of added
      NaF to enough bonding strength of brackets. METHODS: Sixty-four teeth were
      randomly divided into A, B, C and the control group. NaF of four different
      concentrations (1.23%, 2%, 3% and 0%) was added into 35% phosphoric acid. The
      four group teeth were etched with four kinds of fluoride etching fluid
      respectively and were bonded with brackets. Four specimens in each group were
      selected by turns after 1, 4, 12 and 24 weeks of bonding. The shear bond strength
      of the teeth were tested, and the adhesive residual index (ARI) of bonding
      interface were recorded. RESULTS: The shear bond strength at four test time in
      each group was no significant (P > 0.05). There was statistical difference of the
      shear bond strength between four groups (P < 0.05), and group C was lower than
      the other groups. The ARI was no statistical difference between four groups.
      CONCLUSION: The effects of etching and bonding had no significant changes when
      the concentration of added NaF was no more than 2%. The shear bond strength
      decreased while the concentration of NaF was higher than 3%.

PMID- 16285545
TI  - [Study on distribution and drainage of lymphatic vessels of tongue].
AB  - OBJECTIVE: To investigate the distribution and drainage of lymphatic vessels of
      tongue, and to provide anatomical evidence for treatment of tongue cancer.
      METHODS: Indirect lymphatic injection was employed, combined with clearing method
      with winter green oil and corrosive cast technique, to study the distribution of
      lymphatic vessels of tongue. Anatomical methods were used to detect the sentinel
      lymph nodes in different region of tongue. RESULTS: The lymphatic vessels of
      dorsal mucosa composed of lymphocapillary vessels and anstomosing side branches
      were present by superficial and deep capillary networks. The distribution of
      lymphatic networks extend from tip to base and from one board to another, and was
      not influenced by the sulcus tenninalis and median lingual sulcus. Lymphatic
      vessels in the muscular portion communicated with lymphocapillary network of
      dorsal and ventral mucosa, which made the lymphatic vessels of tongue to be an
      integrity network structure. These characters of distribution influenced the
      lymphatic drainage of tongue. The results showed principal sentinel lymph nodes
      (SLNs) for anterior part of tongue were submental lymph nodes, submandibular
      lymph nodes and juguloomohyoid lymph nodes, for lateral part and middle part of
      tongue were submandibular lymph nodes, jugulodigastric lymph nodes and thyroid
      lymph nodes, and for root part of tongue were jugulodigastric lymph nodes. SLNs
      for every injection region were all presented at bilatral neck, but the frequency
      of stained SLNs at homolateral neck was more than that at contralateral neck.
      CONCLUSION: The lymphatic vessels of tongue arranged like a network, which made
      the lymphatic drainage at various ways and made the distribution of sentinel
      lymph nodes to be bilateral and dispersive.

PMID- 16285546
TI  - [Comparison of the suppressive effects of tramadol and low-dose ketamine on the
      patients with postoperative hyperalgesia after remifentanil-based anaesthesia].
AB  - OBJECTIVE: To compare the suppressive effects of tramadol and low-dose ketamine
      on postoperative hyperalgesia after remifentanil-based anaesthesia. METHODS: A
      total number of sixty ASA I - II adult patients who undergone the operation of
      cranio-cervical region were assigned to three groups randomly, controlled group
      (Group C), tramadol group (Group T) and low-dose ketamine group (Group K). Before
      the end of surgery, Group T was given tramadol 0.3 mg/kg, Group K was given
      ketamine 0.5 mg/kg and Group C wasn't given any medicine. When the visual
      analogue scale (VAS) score of the group C was over five, tramadol 0.3 mg/kg was
      given to the patients. The four-level verbal rating scale after trachea
      extubation, VAS score, the time of requiring analgesia again by patients and
      adverse drug reactions such as nausea, vomit, diplopia and hallucination were
      recorded for 24 hours after surgery. RESULTS: After operation, the VAS score of
      Group C was much higher than that of Group K in the first 4 hours and Group T was
      higher than Group K during 2, 3 and 4 hours (P < 0.05). The time of requiring
      analgesia by patients in Group C and Group T was earlier than Group K. The
      adverse drug reaction showed no significant difference in three groups.
      CONCLUSION: Low-dose ketamine had significant suppressive effect on patients with
      postoperative hyperalgesia and acute opioid tolerance after remifentanil-based
      anaesthesia.

PMID- 16285548
TI  - [Clinical use of three-dimensional surface reconstruction of spiral CT for
      impacted teeth in orthodontics].
AB  - OBJECTIVE: To evaluate the value of three-dimensional surface reconstruction of
      spiral CT-shaded surface display (SSD) to examine the impacted teeth before
      orthodontic treatment. METHODS: Three-dimensional surface reconstruction of
      spiral CT and shaded surface display (SSD) was applied to twenty patients whose
      impacted teeth couldn't be judged clearly through the panorama and occlusal
      films. RESULTS: Three-dimensional surface reconstruction of spiral CT and SSD
      could clearly demonstrate the dental surface image including crown, root neck and
      root bifurcation in three-dimensional way, labial or palatal location, eruption
      orientation and relation with dentition. CONCLUSION: It is concluded that the
      three-dimensional surface reconstruction is an accurate and effective method to
      examine impacted teeth before orthodontic treatment.

PMID- 16285547
TI  - [Inhibition effect of methylene blue on the acids production of Streptococcus
      mutans].
AB  - OBJECTIVE: To study the effect of methylene blue on the growth and acid
      production of Streptococcus mutans, and the effect of methylene blue on acid
      production metabolism in plaque glycolysis model (i-PGM) in vitro, and
      investigate the practicability of methylene blue as a new kind of dental caries
      prevention agent. METHODS: Nephelometer method was used to measure OD value of
      Streptococcus mutans culture fluid in the different incubation conditions. The
      kinds and quantities of acid produced by Streptococcus mutans in the different
      incubation conditions were measured with gas chromatography. pH values of
      glycolysis buffer media of i-PGM in the different treatment conditions were
      measured by ORION electrode. RESULTS: (1) The OD value of Streptococcus mutans
      treated by methylene blue was lower than that by normal saline, and there was
      significant statistical difference between them. (2) The kinds of acid in three
      different culture fluid were same, but the total quantities of acid were
      significantly different among three different culture fluid, in which the total
      quantities of acid of culture fluids treated by glucose was the greatest, and
      treated by methylene blue was the lest. (3) The pH value of i-PGM treated by
      methylene blue was significantly different compared with negative control group,
      but was not significantly different compared with positive control group.
      CONCLUSION: Methylene blue can inhibit the growth and acid production metabolism
      of Streptococcus matans and acid production metabolism of i-PGM.

PMID- 16285549
TI  - [Dental arch characteristics of the facial asymmetry].
AB  - OBJECTIVE: To study the characteristics of dental arches in the patients with
      facial asymmetry. METHODS: 20 facial asymmetrical patients were chosen as the
      study subjects. They were 8 boys and 12 girls, aged from 12-year to 16-year old.
      20 normal occlusion persons without signs of facial asymmetry were chosen as
      control. Dental casts were measured by 3-dimension measuring machine. Dental arch
      asymmetry, coordination between upper and lower dental arch, and dental
      inclination were measured. SAS 6.03 was used in statistical analysis. RESULTS:
      The distance from cuspid and the first bicuspid to the median palatal raphe in
      the side of crossbite was larger than that of contralateral side in maxilla. The
      distance from cuspid, bicuspids and the first molar to the midline in the side of
      crossbite was smaller than that of contralateral side in mandible (P < 0.05). The
      dental arch width of cuspid and first premolar in maxilla was smaller than that
      of mandible (P < 0.05) . Significant buccal inclination of the maxillary
      posterior teeth coupled with lingual inclination of the mandibular posterior
      teeth was found on the crossbite side. In contrast, significant lingual
      inclination of the maxillary posterior teeth coupled with buccal inclination of
      the mandibular posterior teeth was found on the contralateral side (P < 0.05).
      CONCLUSION: The width of upper anterior dental arch was smaller, and the
      inclination of upper and lower posterior teeth between crossbite side and
      counterside was different in facial asymmetry patients.

PMID- 16285550
TI  - [Culture and phenotype characteristics of mouse dental follicle cells].
AB  - OBJECTIVE: To establish a method for isolating and culturing mouse dental
      follicle cells and to study the phenotype characteristics of dental follicle
      cells. METHODS: Mandibular first molars from 9 day old Balb/c mice were digested
      with 1% trypsin, subsequently, and the dental follicle was enucleated from the
      tooth germ and cultured. The shape and ultrastructural appearance of dental
      follicle cells were observed under phase-contrast microscope and scanning
      electron microscope (SEM). Immunocytochemistry was used to detect the expression
      of alkaline phosphatase (ALP), bone sialoprotein (BSP) and osteopontin (OPN).
      RESULTS: Three types of cells were isolated: some were cuboidal/polygonal; some
      were elongated, spindle-shaped, fibroblast-like cells; and a minor, third cell
      type was very thin and elongated. The cytoplasm of the first two cell types was
      filled with abundant granules. The cells were pleomorphism under SEM and had many
      filipodia and microvilli. According to whether there were filaments overlying the
      surface, the cells could be divided into two subtypes. Some but not all follicle
      cells expressed ALP, BSP and OPN. CONCLUSION: The cultured dental follicle cells
      consisted of several cell phenotypes and had the potential of differentiating
      into cementoblasts, periodontal ligament fibroblasts and osteoblasts.

PMID- 16285551
TI  - [Mechanisms of p16 gene inactivation salivary adenoid cystic carcinoma].
AB  - OBJECTIVE: To study the mechanism of p16 gene inactivation in salivary adenoid
      cystic carcinoma. METHODS: 53 cases of freshly excised salivary adenoid cystic
      carcinomas were studied. Polymerase chain reaction (PCR) and single-stranded
      conformation polymorphism analysis of polymerase chain reaction products (PCR
      SSCP) were used to detect deletion and mutation of p16 gene in salivary adenoid
      cystic carcinomas. Methylation specific PCR (MSP) was used to detect the
      methylation status of p16 gene. RESULTS: The homozygous deletion, mutation and
      hypermethylation of p16 gene were noted in 16 cases (30.2%), 4 cases (7.5%) and
      26 cases (49.1%) respectively in 53 cases of salivary adenoid cystic carcinomas.
      CONCLUSION: The main inactivation mechanisms of p16 gene in salivary adenoid
      cystic carcinoma were hypermethylation and homozygous deletion. The mutation p16
      gene was rare in salivary adenoid cystic carcinoma.

PMID- 16285552
TI  - [High expression of p65 transcription factor and its significance in tongue
      carcinoma].
AB  - OBJECTIVE: To examine the correlation between p65 expression and the metastasis
      and prognosis in tongue carcinoma. METHODS: The immunohistochemical expression of
      p65 was examined in 50 cases of tongue carcinoma, and the clinical and
      histopathologic records were retrospectively analyzed. RESULTS: Overexpression of
      p65 in cytoplasma and nucleus was found in 64% cases of tongue carcinoma. There
      was significant difference of p65 expression among different TNM stages, and the
      higher expression rate of p65 was found in higher stages. Overexpression of p65
      was also related to lymph node metastasis. Significantly greater increase in
      expression levels of p65 was found in the metastatic cases (n = 22) compared to
      the nonmetastatic cases (n = 10). However, there was no significant difference of
      p65 expression among different histopathologic grading. The 5-year survival rate
      of p65 positive and negative group was 59.3% and 88.9% respectively, and there
      was significant difference in Kaplan-Meier survival curve (chi2 = 5.6, P < 0.05).
      CONCLUSION: The results suggest that the expression of p65 was important to
      predict the metastasis and prognosis in tongue carcinoma.

PMID- 16285553
TI  - [Quantitative study of alkaline phosphatase and osteocalcin in the process of new
      bone].
AB  - OBJECTIVE: Alkaline phosphatase (ALP) and osteocalcin (OC) are the markers of new
      bone formation. Quantitative study of ALP and OC in the process of new bone
      formation helps to understand the ongoing of this cascade and contributes to make
      diagnosis in clinical treatment. METHODS: 8-week-old male C57BL/6J mice and
      primary osteoblasts from neonatal C57BL/6J mice calvaria were used in this
      experiment. HE staining, Northern blot and Real Time PCR methods were employed to
      detect the histological changes and the expression pattern of ALP and OC.
      RESULTS: In vivo study showed that after fracture the expressions of both ALP and
      OC kept on increasing which were peaked on the 10 day, then started decreasing
      gradually. In vitro study on primary osteoblasts showed that the expressions of
      ALP and OC reached peak on the 14th day in differentiation culture medium and
      started decreasing from this time point till the 21st day. CONCLUSION: The
      expression of ALP and OC in the process of new bone formation parallels with the
      development of osteoblasts, it increases with the differentiation of osteoblasts
      and becomes decreasing with the maturation of osteoblasts. The reciprocal
      relationship between the expression pattern of ALP and OC and development of
      osteoblast helps to maintain homeostasis.

PMID- 16285555
TI  - [Relationship between the expression of cyclooxygenase-2 and microvessel density
      in oral squamnous cell carcinoma].
AB  - OBJECTIVE: To detective the relationship between cyclooxygenase-2 (COX-2) and
      angiogenesis in oral squamous cell carcinoma (OSCC) and its clinical significance
      through observing the expression of COX-2 and determining microvessel density
      (MVD) in OSCC. METHODS: PV-9000 immunohistochemistry was used to determine the
      expression of COX-2 and CD34, which was used to determine MVD, in 76 OSCC tissues
      and 12 normal oral mucosa tissues. RESULTS: Overexpression of COX-2 was detected
      in OSCC, and was more intense compared with normal epithelium (P < 0.001). The
      high expression of COX-2 in OSCC was related to neck lymphnode metastasis, tumor
      size, TNM stage and histological grade (P <0.05). The MVD value in COX-2-positive
      group was much higher than that in COX-2-negative group (P < 0.01) and that in
      normal oral mucosa tissues (P < 0.01). CONCLUSION: The high expression of COX-2
      in OSCC was significantly associated with MVD, neck lymphnode metastasis, tumor
      size, TNM stage and histological grade. COX-2 might be one of the important
      factors in the angiogenesis of OSCC.

PMID- 16285554
TI  - [Evaluation on cytotoxicity of a new nano-hydroxyapatite as root canal filling
      sealer].
AB  - OBJECTIVE: To evaluated the cytotoxicity of a new nano-hydroxyapatite (n-HA) root
      canal sealer. METHODS: In this study, the cytotoxicity was evaluated by the
      method of MTT assay in vitro, and culture medium F12 as control, three
      concentrations of the soaking material cultured with mouse osteoblast separately,
      to test the cell relative growth rate (RGR) of every group. RESULTS: The toxicity
      graduation of the n-HA root canal sealer tends to 0 with the culture time
      increasing. The cell survival rate of n-HA root canal sealer showed high
      relatively. The OD value of cell was similar for the negative control and the
      extracts (P > 0.05). CONCLUSION: The result indicated that n-HA root canal sealer
      was compatible with the testcells.

PMID- 16285556
TI  - [Study on mRNA expression of fibronectin and integrin beta1 during fracture
      healing].
AB  - OBJECTIVE: To investigate the spatial and temporal expression changes of
      fibronectin and integrin beta1 mRNA during fracture healing. METHODS: Using in
      situ RT-PCR technique, the spatial and temporal expression pattern of both
      fibronectin and integrin beta1 mRNA was detected on paraffined slices in
      different rabbit mandibular fracture healing phases. RESULTS: (1) The mRNA of
      integrin beta1 and fibronectin was widely expressed in fractured bone cells. The
      positive stain existed in cytoplasm and nucleolus. (2) After 7 days of fracture,
      increaseded integrin beta1 mRNA expression was observed, and it reached maximal
      levels approximately 14- 30 days post-fracture and returned to normal levels
      after 60 - 90 days. (3) Fibronectin mRNA was detected on 3 days post-fracture, it
      reached maximal levels at 7 - 14 days, faint expression was detected at 30 days,
      undetectable 60 days afterwards. CONCLUSION: During fracture healing, the mRNA
      expression of integrin beta1 and fibronectin increased locally, FN and Itg beta1
      cooperate with each other, it is suggested that they have an important influence
      on fracture healing.

PMID- 16285557
TI  - [Histological evaluation of direct pulp capping with a self-etching adhesive and
      calcium hydroxide].
AB  - OBJECTIVE: To evaluate the beagles' pulp response following direct pulp capping
      with Clearfil SE BOND (SB). METHODS: 130 sound teeth were used. 120 had their
      pulps mechanically exposed and were divided in two groups. In group A, teeth were
      capped with SB. In group B, teeth were capped with calcium hydroxide (CH). The
      left 10 teeth were used as control. After 7, 30 and 90 days, the teeth were
      extracted and processed for light microscopical examination. RESULTS: In 7 day
      observation period, inflammatory reaction in SB group was slighter than that of
      CH group, but the difference was statistical insignificant. In the 30 day and 90
      day observation period, inflammatory reaction was slight in both groups, but
      specimens with dentin bridge formation was significantly less in SB group than in
      CH group (P < 0.05). CONCLUSION: SB showed acceptable biocompatibility with pulp,
      but its ability to induce hard tissue barrier on pulp exposure is weaker than CH.

PMID- 16285558
TI  - [Effects of arsenic trioxideon the cell apoptosis and hTERT mRNA of human tongue
      cancer cells].
AB  - OBJECTIVE: To study the effects and its mechanisms of arsenic trioxide (As2O3) on
      cell growth and human telomerase reverse transcriptase (hTERT) of human tongue
      cancer cells (Tca8113 cell line). METHODS: The growth inhibition rates of Tca8113
      by various concentrations of As2O3 were detected by MTF method. Cell apoptosis
      was detected by FCM labeled with Annexin V-FITC. hTERT gene expression was
      detected by RT-PCR method. hTERT protein of Tca8113 cells was determined by
      Western blot assay. RESULTS: The results showed that As2O3 could inhibit the
      growth of Tca8113 effectively and apoptotic rate of Tca8113 cells was obviously
      increased in a dose and time-dependent manner. (83.40 +/- 7.31)% cells treated
      with 5 micromol/L As2O3 were inhibited on 72 hour point, the early apoptosis rate
      reached on 26.40% +/- 3.42% at that time. Moreover hTERT mRNA and protein were
      decreased depended on the dose and time of As2OC3, mRNA expressions of hTERT in
      test groups were greatly lower than that of control group on 72 hour point.
      CONCLUSION: It was suggested that As2O3 could significantly inhibit the growth of
      Tca8113 cells by inducing causing cell apoptosis and down-regulating the
      expression of hTERT mRNA gene and protein which might be one of its action
      mechanisms.

PMID- 16285559
TI  - [Experimental study of cisplatin loaded polylactic acid-polyethylene glycol nano
      particles for targeting oral carcinoma].
AB  - OBJECTIVE: To investigate the target deliver of Cisplatin to oral carcinoma
      tissues by intravenous injection of Cisplatin loaded polylactic acid-
      polyethylene glycol nanoparticles (CDDP-PLA-PEG-NP). METHODS: CDDP-PLA-PEG-NP was
      prepared by the emulsion-solvent evaporation method. The buccal cancer model was
      established in 64 golden hamsters, which were divided randomly into two groups
      for 32 animals in each group, CDDP-PLA-PEG-NP (6.6 mg/kg) and CDDP (1 mg/kg) were
      respectively injected into mice tail vein. At 0.083, 0.5, 1, 2, 4, 6, 12, 24 h
      after drug administration. 4 animals in each group were sacrificed and CDDP
      concentration in the plasma and tumor were determined by high performance liquid
      chromatography. Targeting ability was evaluated by targeting index (TI),
      selectivity index (SI) and relative extraction efficiency (re). RESULTS: The
      average diameter of CDDP-PLA-PEG-NP was (143.2 +/- 1.8) nm. The diameter
      distribution was from 103.5 nm to 175.8 nm. Drug loading and embedding ratio were
      (15.2 +/- 0.9) %, (89.0 +/- 0.8) % respectively. Values of TI and SI are more
      than 1 at 8 time points. The area under CDDP concentration-time curve of oral
      carcinoma tissues in CDDP-PLA-PEG-NP group was 10.36 times as many as that in
      CDDP group. CONCLUSION: CDDP-PLA-PEG-NP can specifically deliver CDDP to oral
      carcinoma tissues by vein injection. Stealth anticancer nano-particle system can
      be regarded as a valuable drug deliver system to treat oral carcinoma.

PMID- 16285560
TI  - Conservative management of epithelial ovarian cancer.
AB  - We are currently faced with a progressive delay in the age at which women
      conceive for the first time. This raises the possibility of the appearance of
      gynecologic disorders that may affect fertility, including neoplasms of the
      ovary. Fertility-sparing surgery is defined as the preservation of ovarian tissue
      in one or both adnexa and/or the uterus. Borderline ovarian tumor should be
      treated with conservative surgery. Salpingo-oophorectomy, or even ovarian
      cystectomy, are the procedures of choice, with recurrence rates of 2-3% and up to
      20% if a simple cystectomy is performed. Cystectomy is indicated in patients with
      bilateral borderline tumors or in patients with a residual ovary. Borderline
      tumors with invasive peritoneal implants behave as an invasive cancer in 10-30%
      of cases with a survival rate of 10-66% compared with 100% in borderline tumors
      without invasive implants. Prophylactic oophorectomy is recommended when desire
      of conception has been accomplished. Conservative surgery in invasive epithelial
      ovarian cancer is limited to Stage IA, grade 1 tumor, and in some highly selected
      grade 2 tumors of serous, mucinous or endometrioid type, well-encapsulated and
      free of adhesions. The standard oncological surgical procedure with preservation
      of the uterus and normal appearing ovary is recommended. This includes salpingo
      oophorectomy, excision of any suspicious peritoneal lesion, multiple peritoneal
      biopsies, appendectomy (particularly in mucinous tumors), and pelvic and
      paraaortic lymphadenectomy.

PMID- 16285561
TI  - Endometrial cancer: asymptomatic endometrial findings. Characteristics of
      postmenopausal endometrial cancer.
AB  - Endometrial cancer affects patients at every age, however it occurs more
      frequently in menopause (> 50) and in postmenopause (> 70). The most frequent
      symptoms are bleeding and vaginal discharge. When hematometra or pyometra is
      present the patient may feel pain. In some cases endometrial adenocarcinoma is
      asymptomatic and the diagnosis is casually made during ultrasound examination or
      by histological examination of a uterus surgically removed for other indications.
      In these cases the most frequent findings are polyps and abnormally increased
      thickness of the endometrial mucosa. In postmenopause polyps and abnormal
      endometrial thickness are usually limited to a small area and surrounded by
      atrophic mucosa. Higher incidence rates of endometrial cancer were correlated
      with polyps and an increased number of serous type tumors were identified in the
      > 65-year age group. Endometrial carcinoma may be estrogen correlated or non
      estrogen associated. Patients in postmenopause are often affected by non-estrogen
      correlated endometrial carcinoma. According to Kurman and other authors the first
      type of endometrial adenocarcinoma (estrogen correlated) is characterized by low
      grade malignancy. On the contrary, non-estrogen correlated neoplasia is more
      aggressive. In our case series including 102 women aged > 70 years with
      endometrial carcinoma we found that survival was correlated with stage and
      grading - early stages were the most frequent and the grade increased with stage.
      In fact all the patients with relapses had grade 2 or 3 adenocarcinomas. Thirty
      one patients > 70 years (30.69%) had a non-endometrioid type of cancer.

PMID- 16285562
TI  - Breast density changes associated with hormone replacement therapy in
      postmenopausal women. Effects on the specificity and sensitivity of mammographic
      screening.
AB  - Postmenopausal HRT use is associated with an increase of mammographic density and
      reduction of sensitivity and specificity of mammography results and an increase
      of false-positive and false-negative outcomes. The increased density does not
      allow a good evaluation of the exam. Mammographic density is an independent risk
      factor for breast cancer, but the link between changes in breast density and
      difference in breast cancer risk, remain uncertain. On the other hand, today
      specific guidelines and protocols to optimize the screening of neoplastic breast
      pathology in HRT users do not exist and it is unknown if short-term suspension of
      therapy improves mammographic sensitivity. More information is required to define
      this important risk factor.

PMID- 16285564
TI  - Radical hysterectomy for cervical carcinoma in pregnant women--a case of decidua
      mimicking metastatic carcinoma in pelvic lymph nodes.
AB  - Intraoperative histology is commonly used to guide the treatment of women with
      carcinoma of the cervix. We present a case where frozen section of the pelvic
      lymph nodes from a pregnant woman was suggestive of metastatic cervical carcinoma
      but final histology showed only decidual change.

PMID- 16285563
TI  - Factors predicting persistence of high-risk human papillomavirus (HPV) infections
      in women prospectively followed-up in three New Independent States (NIS) of the
      former Soviet Union.
AB  - BACKGROUND: We completed an analysis of the factors predicting the persistence of
      high risk (HR) HPV infections in women participating in a multicenter screening
      trial in three NIS countries. METHODS: The 543 baseline HR HPV-positive women
      included in this analysis are derived from a sub-cohort of 887 women who were
      prospectively followed-up for a mean of 21.6 months (range: 0.5-42.9) as a part
      of a multi-center screening study in three NIS countries (the NIS cohort study; n
      = 3,187 women). Of these 543 women, 273 showed persistent HR-HPV in serial Hybrid
      Capture II (HCII) testing during the follow-up (Group 1), whereas 270 women
      cleared their infection (Group 2). These two groups were compared with their
      epidemiological, clinical, and virological data (HCII, PCR) to disclose the
      factors predicting persistent HR-HPV infection. RESULTS: Women with persistent HR
      HPV infections were significantly younger (27.3 yrs) than those who cleared their
      infection (29.1 yrs) (p = 0.006), and their follow-up time was shorter; 14.1 and
      21 months, respectively (p = 0.0001). Both variables were treated as confounders
      in the multivariate analyses. Of the 66 recorded epidemiological variables, only
      being a current smoker proved to be an independent predictor (OR 1.693; 95% CI
      1.114-2.573; p=0.014). Baseline colposcopy, biopsy or Pap smear did not predict
      HPV persistence, whereas an incident or persistent abnormal Pap during the follow
      up were independent predictors in a multivariate model (p = 0.005), together with
      the high viral load (HCII RLU/CO at 100 pg/ml cut-off), and HR HPV positive PCR
      test (p = 0.0001). When all significant variables were entered in the regression
      model, only the follow-up time (OR 0.950, 95% CI 0.924-0.976; p = 0.0001) and HR
      HPV positive PCR (OR 4.169, 95% CI 1.741-9.987; p = 0.001), remained independent
      predictors. CONCLUSIONS: While several factors were related to HR-HPV persistence
      in univariate analysis and when adjusted for age and follow-up time as
      confounders, the only independent predictors in the multivariate regression model
      were follow-up time and HR-HPV positive PCR. Clearly more data are needed on type
      specific persistence and HPV integration as its predictors.

PMID- 16285565
TI  - Differential gene expression assessed by cDNA microarray analysis in breast
      cancer tissue under tamoxifen treatment.
AB  - Our purpose was to identify tamoxifen (TAM) responsive genes after 30 days of TAM
      treatment in tumor tissues obtained from women with breast cancer using
      microarray expression analysis. In our study, we identified 12 candidates to be
      considered as tamoxifen-modulated genes. Among them, we selected two candidates
      the TEGT BI-1 (testis enhanced gene transcript Bax Inhibitor-1) and the CD63 gene
      in order to further confirm their differential expression under tamoxifen
      effects. We observed that both were down-regulated in tumor tissues of patients
      during TAM treatment. TEGT is able to inhibit the expression of Bax, which is
      known to promote apoptosis. On the other hand, CD63 encodes a cell membrane
      protein and it seems to be involved in mechanisms of platelet activation, cell
      adhesion and cell motility. We therefore hypothesize that TAM would be able to
      modulate tumor growth by down-regulating genes involved in mechanisms such as
      cell cycle control, tumor invasion and metastasis.

PMID- 16285566
TI  - Epidemiology of malignant breast tumors in the province of Sassari (Sardinia,
      Italy) in the period 1992-2002.
AB  - The aim of this study was to evaluate the incidence of malignant breast tumors in
      the Province of Sassari, Sardinia (Italy) in the period 1992-2002 and to report
      the variations in comparison to the 1974-1985 period. The analysis of our data
      showed that the overall number of malignant breast tumors was more than doubled
      from 1,139 cases in the period 1974-1985 to the 2,735 cases in the period 1992
      2002, and the mean rate/100,000 changed from 43.4 to 106.0. The incidence in the
      age classes 45-64 years, which were at enhanced risk for breast cancer, was
      globally increased, changing from 143.6/100,000 to 198.7/100,000. On the other
      hand, the incidence in the youngest age classes (30-34 yrs) was reduced from
      59.5% to 27.0%. The analysis of the histotypes showed a relative reduction of
      ductal carcinoma in the period 1992-2002 in comparison to the previous period
      1974-1985 (65.2% vs 82.0%) whereas the incidence of anaplastic forms increased in
      advanced ages of life. We reported an important reduction of T0 tumors from 3.4%
      to 0.1%. These data could be due to the low diffusion of screening programs in
      Sardinia. Tumor metastases were more frequent in advanced age classes. In
      conclusion, the worrying data of the strong reduction of T0 cases, the increased
      age of first diagnosis and the advanced forms with positive nodal metastases
      showed that the prevention program has not been yet well organized.

PMID- 16285567
TI  - Primary peritoneal malignant mixed mullerian tumor associated with colonic
      adenocarcinoma.
AB  - BACKGROUND: Primary extragenital malignant mixed Mullerian tumors (MMMTs) are
      very rare neoplasms, with only 28 documented cases in the literature. Two cases
      coexisted with a colonic adenocarcinoma. CASE: We report on a primary peritoneal
      MMMT diagnosed shortly after resection of a colonic adenocarcinoma in an 85-year
      old woman who presented with a large omental mass. Microscopic examination
      revealed a biphasic tumor with malignant carcinomatous and sarcomatous
      components, confirmed immunohistochemically, consistent with MMMT. Despite
      optimal debulking and uneventful postoperative recovery, the patient died of her
      disease shortly after surgery due to recurrent disseminated disease. CONCLUSIONS:
      This is the third case in the literature of primary extragenital MMMT occurring
      in association with colonic adenocarcinoma. This coexistence may be incidental,
      but it may also imply a possible linkage between these two tumors.

PMID- 16285568
TI  - Adenofibromasarcoma originating from a mural nodule of ovarian serous
      cystadenoma.
AB  - A 83-year-old woman received bilateral salpingo-oophorectomy and hysterectomy due
      to a provisional diagnosis of ovarian cystic tumor. The tumor had a unilocular
      cystic cavity demonstrating serous cystadenoma and a solid mural nodule
      representing a biphasic pattern with mesenchymal and glandular components. The
      glandular elements were composed of benign serous cells, whereas the mesenchymal
      components consisted of an admixture of fibromatous stromal cells without atypia
      and sarcomatous overgrowth. The area of transition from a fibromatous component
      to sarcomatous overgrowth was identified. After a 2-year follow-up, there were no
      signs of tumor recurrence or systemic disease. To the authors' knowledge, this is
      the first reported case of adenofibrosarcoma originating from a mural nodule of
      ovarian serous cystadenoma.

PMID- 16285569
TI  - Biphasic sarcomatoid carcinoma or carcinosarcoma of the breast: prognosis and
      therapy.
AB  - Biphasic sarcomatoid carcinoma of the breast represents only 0.2% of all breast
      cancer. Due to its rarity and repetitive reclassifications little is known about
      optimal treatment modalities. These tumours form a diagnostic and therapeutic
      challenge. The present report describes our experience with a case of biphasic
      sarcomatoid carcinoma of the breast and a review of the relevant literature is
      discussed.

PMID- 16285571
TI  - Ingenol derivatives inhibit proliferation and induce apoptosis in breast cancer
      cell lines.
AB  - We present an analysis of the antitumour effects of a library of ingenol
      derivatives synthesized in our laboratory and published elsewhere. Fluoro-ingenol
      (1), ingenol-20-deoxy-20-phtalimido (2), ingenol-3-benzoate-20-deoxy-20-benzamide
      (3), ingenol-3-benzoate (4), ingenol-3,5-dibenzoate (5), ingenol-3,20-dibenzoate
      (6), 20-deoxy-20-benylureidoingenol-3-benzoate (7), ingenol-20-deoxy-20-fluoro-3
      benzoate (8), ingenol-20-deoxy-20-fluoro-3,5-dibenzoate (9), ingenol-20
      phenylcarbamate (10), ingenol-20-benzoate (11), ingenol-3-benzoate-20
      phenylcarbamate (12) were tested in vitro on two well characterized breast cancer
      cell (BCC) lines, namely T47D and MDA-MB-231, as representative of two opposite
      types of hormone-sensitiveness and differentiation stage. These experiments led
      us to identify ingenol-20-benzoate (11) as a promising antitumour compound
      characterized by a relevant inhibition of cell growth and apoptotic cell death
      involving a p53-mediated pathway.

PMID- 16285570
TI  - Further studies on leptin and leptin receptor expression in myometrium and
      uterine myomas.
AB  - AIM: Examination of the potential role of leptin in the development of uterine
      myomas. Expression of the leptin gene and leptin receptor gene was tested in the
      myometrium of healthy women, and in myomas and the surrounding myometrium of
      women with benign tumors. METHODS: Using RT-PCR, expression of the leptin gene
      and leptin receptor gene were studied in myomas and in the surrounding myometrium
      in 30 women with uterine myomas at various phases of the menstrual cycle, and in
      the myometrium of ten women in a control group. Presence of leptin gene proteins
      and leptin receptor gene proteins in the women was also examined by Western
      blotting. RESULTS: Using RT-PCR, expression of the leptin gene was demonstrated
      both in myomas and in the surrounding myometrium. In contrast, expression of the
      gene could not be detected in the myometrium of healthy women. The results were
      confirmed by Western blotting, which documented the identical distribution of
      leptin proteins and leptin receptor proteins in studied tissues. CONCLUSION:
      Demonstration of the expression of leptin genes and leptin proteins in uterine
      myomas and in the surrounding myometrium, and their absence in the myometrium of
      healthy women suggests the involvement of leptin in the development of uterine
      myomas.

PMID- 16285572
TI  - Syndrome of inappropriate secretion of anti-diuretic hormone following
      carboplatin-paclitaxel administration in a patient with recurrent ovarian cancer.
AB  - This is the first report on a syndrome of inappropriate secretion of anti
      diuretic hormone (SIADH) in a patient with recurrent ovarian cancer following
      carboplatin and paclitaxel administration. A 63-year-old woman received
      chemotherapy combining carboplatin and paclitaxel for recurrent ovarian serous
      papillary adenocarcinoma. Four days after the chemotherapy, she suffered
      decreased mental awareness and lost consciousness. Blood chemistry tests showed
      serum sodium of 109 mmol/l. Plasma osmolarity was reduced to 232 mOsm/kg while
      urine osmolarity was high at 430 mOsm/kg, strongly suggesting the presence of
      SIADH. Because hyponatremia was not observed in the subsequent cycle of
      chemotherapy consisting of weekly paclitaxel and cisplatin, carboplatin was
      thought to be responsible for the condition. Clinicians should be aware of the
      possibility that carboplatin may cause SIADH, and should carefully monitor
      electrolyte balance after chemotherapy.

PMID- 16285573
TI  - Koilocytosis and squamous (pre)neoplasia as detected in population-based cervical
      screening: practice and theory.
AB  - INTRODUCTION: Koilocytosis (cavitation of the cytoplasm due to active HPV
      infection) can be detected in the screening process for cervical carcinoma.
      OBJECTIVE: To report the practice of detection of koilocytosis and (pre)neoplasia
      in population screening and to exploit the collected data to propose an
      explanation for the relationship between HPV infection and nuclear precancerous
      changes. STUDY DESIGN: Centrally collected and stored (SBBW, Leiden, the
      Netherlands) data from all smears of six regional pathology laboratories (1995
      2002), coded according to KOPAC (the national cervical smear coding system; S1:
      normal thru S9: invasive carcinoma) were accessed. Prevalences per 100,000 smears
      were calculated for koilocytosis and for squamous abnormalities after
      stratification for country of origin of screenees. The relative risk (RR) for the
      ethnic (age) groups was computed by dividing the prevalence of the relevant
      ethnic (age) group by the prevalence of all women. RESULTS: Surinamese women
      featured the highest prevalence of koilocytosis and of all squamous
      abnormalities. Moroccan women the lowest. The RR for koilocytosis was highest at
      30 years (1.84) and lowest at 60 (0.26). RR dependence on age of S5-S9 lesions
      was similar. Compared to nonkoilocytotic smears, koilocytosis was 104 times more
      frequent in the 1,500 S4 smears, 36x more frequent in the 6,700 S2-S3 smears, and
      24x more frequent in the 1,740 S5-S9 smears. In all three categories this
      difference is statistically significant. CONCLUSION: High prevalences for both
      koilocytosis and for preneoplasia were detected in Surinamese immigrants,
      however, it still does not exclude HPV infection as a confounder linked to sexual
      lifestyle. The presence of koilocytosis in cervical smears may serve to identify
      patients with an increased risk for cervical cancer and perhaps warrant more
      intensive surveillance than what is provided through five-yearly screening.

PMID- 16285574
TI  - Clinical audit of patients with cervical cancer in Slovenia--data analysis for
      the year 2003.
AB  - PURPOSE OF INVESTIGATION: The data gathered in 2003 on the patients with cervical
      cancer who regularly attended their gynecologist were analyzed with the purpose
      of clinical audit. METHODS: The data on newly detected patients with cervical
      cancer in 2003 who regularly attended their gynecologist were gathered
      simultaneously at three Advisory Boards for Gynecology in Slovenia. RESULTS: Of
      149 patients in whom, according to our data, invasive cervical cancer had been
      diagnosed, 92 (61.7%) patients were examined by a gynecologist in the previous
      five years. In the majority of these patients, cervical cancer was diagnosed in
      early, localized disease stage. In the periods of 13-24 and of seven to 12 months
      before the diagnosis of cervical cancer, almost half the patients had Pap II, and
      three to six months before diagnosis, 67.6% of patients had Pap II. CONCLUSION:
      These results encourage us to proceed with clinical audits to analyze individual
      cervical cancer cases, including another independent reevaluation of cervical
      smears in the five-year period before diagnosis. A suitable calendar of refresher
      training courses on colposcopy, which should be obligatory for all performing
      this examination method, also needs to be set up.

PMID- 16285575
TI  - Postmenopausal bleeding and vaginal nodules as the first presenting sign of
      adenocarcinoma of the gallbladder.
AB  - Vaginal submucosal nodules were observed in a 67-year-old woman, with
      ultrasonographic features of an advanced uterine neoplasm. On biopsy, light
      microscopy suggested that the lesions might be metastatic foci from an
      extragenital cancer, with a prevalent tubular growth pattern. Parallel
      immunohistochemical reactions revealed a diffuse, strong CA 19-9 positivity in
      both the cell membrane and cytoplasm. Subsequently, high serum levels of such
      tumor marker were also found, and an extragenital cancer was suspected of
      pancreatic or biliary origin. A mass in the gallbladder fossa was then detected
      by computed tomography and a primary gallbladder adenocarcinoma was confirmed on
      ultrasound-guided biopsy.

PMID- 16285576
TI  - Hysterectomy in a malignant molar pregnancy and a healthy baby.
AB  - Hydatidiform mole is a degenerative chorion disturbance of unknown etiology. It
      is characterized by a permanent whitish enlargement of the chorionic villi with a
      grape-like appearance and poor vascularization. The symptoms of a molar pregnancy
      are nausea and vomiting which are present in more than one-third of the patients.
      Other symptoms include an enlarged uterus and vaginal bleeding. Our patient was a
      19-year-old primipara with a twin pregnancy where one embryo was molar. Diagnosis
      was confirmed by beta-hCG levels.

PMID- 16285577
TI  - Metastatic disease in the breast from nonmammary neoplasms.
AB  - Breast cancer is the leading cause of death from cancer in women. The metastatic
      involvement of the breast from nonmammary neoplasms is a relatively rare
      condition. Female patients are affected five to six times more frequently than
      male patients. We present seven patients with metastasis in the breast from
      extramammary tumors. Females seemed to be more frequently affected (6 women and 1
      man) and included a wide range of ages (17-70 years old). All female patients had
      suspicious-looking abnormalities (B1-RADS 4) or lesions highly suspicious of
      malignancy (BI-RADS 5) in the mammography, without a confirmative fine needle
      aspiration cytology. The primary malignancies were equally distributed between
      non-hematological (1 renal adenocarcinoma, 1 melanoma, 1 leiomyosarcoma) and
      hematological (1 non-Hodgkin's, 2 Hodgkin's lymphomas and 1 leukemia). Treatment
      is therefore modified, taking into consideration the treatment and prognosis of
      the primary disease.

PMID- 16285578
TI  - Cervical carcinoma and pregnancy in a young primipara.
AB  - Cervical carcinoma is the fourth most common malignant disease in women, after
      breast, lung and colon cancer. It is present in two-thirds of all malignant
      diseases of the genital tract. Although in most of Europe patients are subjected
      to regular health screening, diagnoses of severe life-threatening alterations are
      often made when they are already in late stages.

PMID- 16285579
TI  - Gherlin expression in women with polycystic ovary syndrome--a preliminary study.
AB  - The etiology and pathogenesis of polycystic ovary syndrome (PCOS) is still
      unknown. Using real-time PCR, we detected that polycystic ovaries showed almost
      ten times lower expression of ghrelin mRNA than normal ovaries, whereas the mRNA
      levels in blood cells were similar in both study groups. This suggests that the
      presence of ghrelin in PCOS and normal ovaries may have an autocrine/paracrine
      modulatory effect on ovary functions and local significance in the etiology of
      PCOS.

PMID- 16285580
TI  - Breast cancer in the elderly.
AB  - The study population was derived from 482 patients with breast cancer treated at
      the Department of Oncology, University Hospital Center Zagreb, between 1992 and
      1999. The main purpose of our study was to evaluate differences in breast cancer
      characteristics and treatment in a population of women with breast cancer older
      than 65 years compared to younger women group (less than 65 years). We have
      analyzed disease parameters (stage of the disease, size of primary tumor, tumor
      differentiation grade and steroid receptor status) and parameters associated to
      treatment modalities (surgery, radiotherapy, hormonal therapy and chemotherapy)
      in both age groups. In older women, we found significantly higher rates of tumors
      grade 1 (p = 0.0049), tumors > 2 cm and tumors with a high steroid receptor
      status (p = 0.0013). Evaluation of treatment modalities showed that in older
      women a significantly higher proportion were treated with hormonal therapy (p <
      0.001) compared to younger patients. In evaluation of clinical outcome after a
      median follow-up of 58 months, in older women the cumulative 5-year disease-free
      survival rate was 65%, while cumulative 5-year survival was 83%, which was not
      significantly different from the younger women (p > 0.005).

PMID- 16285581
TI  - Incidence of endometrial carcinoma in patients with endometrial hyperplasia.
AB  - OBJECTIVE: The purpose of this retrospective study was to establish the risk of
      developing endometrial adenocarcinoma in patients diagnosed with endometrial
      hyperplasia. MATERIAL AND METHODS: The incidence of endometrial hyperplasia and
      its relation with endometrial adenocarcinoma was evaluated in 1,139 patients who
      presented with abnormal bleeding between January 2000 and December 2004; D&C was
      performed in all cases. There were 591 (51.88%) cases of simple endometrial
      hyperplasia, out of which 110 (18.61% from 51.88%) cases had atypia, 60 (5.26%)
      cases of complex hyperplasia, out of which 19 (31.66% from 5.26%) had atypia, and
      the remaining 488 (42.84%) had different forms of mixed hyperplasia. RESULTS: The
      incidence of endometrial adenocarcinoma was 3.87% in atypical hyperplasia and
      0.81% in other forms, and was related only to cases with atypia in which the
      incidence was 0.61%. CONCLUSIONS: The most indicated measure to prevent
      endometrial carcinoma in cases with complex endometria hyperplasia with atypia is
      hysterectomy, while for other forms of hyperplasia, hormonal treatment is used
      but only under strict control.

PMID- 16285582
TI  - Saline contrast hysterosonography in infertile patients and in women with
      abnormal uterine bleeding.
AB  - OBJECTIVE: We conducted this prospective study to evaluate saline contrast
      hysterosonography (SCHS) as a diagnostic modality for intrauterine lesions in
      comparison to hysteroscopy and endometrial biopsy. MATERIALS AND METHODS: We
      included 135 patients, of whom 70 presented with abnormal uterine bleeding and 65
      with subfertility problems. All cases were examined with conventional
      transvaginal sonography and were further investigated with SCHS using saline as
      contrast medium, and finally hysteroscopy with endometrial biopsy that was used
      as the reference test. RESULTS: SCHS revealed the presence of intrauterine
      pathology in 23 cases and failed in three (4.2%). SCHS had a sensitivity of 94%,
      a specificity of 71%, a positive predictive value of 76% and a negative
      predictive value of 95% in the abnormal uterine group. In subfertile patients,
      SCHS revealed the presence of intrauterine pathology in 34 cases and had a
      sensitivity of 96%, a specificity of 74%, a positive predictive value of 79% and
      a negative predictive value of 95%. CONCLUSIONS: We found that SCHS is an
      extremely accurate modality for the diagnosis of focal endometrial pathology,
      compared to diagnostic hysteroscopy.

PMID- 16285583
TI  - Pedunculated aggressive angiomyxoma arising from the vaginal suburethral area:
      case report and review of literature.
AB  - BACKGROUND: Aggressive angiomyxoma (AA) is an uncommon, slow growing, locally
      infiltrative but non-metastasizing, distinctive mesenchymal tumor that
      predominantly affects the pelvis and perineum of premenopausal women. The
      mainstay of treatment is local excision with tumor-free margins; however,
      recurrences are common and related to inadequate primary excision. CASE: A
      pedunculated 3-cm mass arising from the vaginal suburethral area in a 49-year-old
      premenopausal woman was resected around the base of its pedicle. Microscopic
      examination revealed numerous blood vessels of various sizes set in myxoid stroma
      with spindle shaped fibroblasts. Immunohistochemical staining was strongly
      diffusely positive for vimentin, desmin, estrogen receptor (ER) and progesterone
      receptor (PR), weakly focally positive for CD34, and negative for S-100 protein,
      actin and Ki-67. These findings are compatible with the diagnosis of AA. To date,
      six months after surgery, the patient is alive and without evidence of
      recurrence. CONCLUSIONS: AA is often clinically misdiagnosed and it is only the
      microscopic examination strengthened with immunohistochemical staining that
      definitely and undeniably contributes to the final diagnosis of AA. Based on this
      case report and on the previously reported five cases of pedunculated AA arising
      from the vulvovaginal region, including one tumor arising from the vaginal
      suburethral area, it seems that pedunculated AAs arising from the vulvovaginal
      region are at negligible risk of recurrence after local excision.

PMID- 16285584
TI  - Sequential recurrences of ovarian granulosa cell tumour 10 and 11 years after
      initial diagnosis as haemoperitoneum and subhepatic mass: a case report and
      review of the literature.
AB  - Adult granulosa cell tumours (GCTs) are rare ovarian neoplasms characterised by
      an indolent course and a propensity for late recurrence. Due to frequent
      endocrine manifestations most GCTs are diagnosed at an early stage. However,
      clinical behaviour can not be safely predicted on the basis of conventional
      clinicopathologic parameters. Surgery remains the cornerstone of therapeutic
      management. We report on a rare case of a Stage IA GCT twice recurring ten and 11
      years after initial surgical treatment. The first recurrence presented as an
      acute abdomen due to haemoperitoneum after tumour rupture. The second recurrence
      presented as a subhepatic mass. This case emphasises the need for extended,
      lifelong follow-up even for patients with early stage, apparently completely
      removed GCTs. Prognostic parameters and therapeutic options especially for
      patients with recurrent disease are discussed.

PMID- 16285585
TI  - Leiomyosarcoma of the vulva: a case report.
AB  - Primary sarcoma of the vulva is a rare tumor. Leiomyosarcoma is the most common
      histologic variant of vulvar sarcoma. The patient, a 55-year-old, gravida 4, para
      2 postmenopausal Greek woman, presented with a 5-year history of progressive
      enlargement of the right labia majora. On vaginal examination there was a 8 x 9
      cm raised, ulcerated and irregular mass of the right labia majora. Despite
      surgery, the patient died six months later because of multiple metastases.

PMID- 16285586
TI  - Breast cancer and borderline ovarian carcinoma in young patients--case report.
AB  - Cystosarcoma phyloides is a breast cancer with deterrent features because of its
      size and fast growth. Borderline ovarian tumors comprise 10% to 15% of all
      epithelial tumors of the ovary. Regardless of the tumor type (serous, mucinous,
      clear cell, Brenner, mixed) they can be benign, borderline or malignant. There is
      a close physiological relation between the breasts and genital tract. By routine
      examination of girls in secondary schools, suspected ultrasonography findings
      were found in two out of 180 examinees.

PMID- 16285587
TI  - [Clinicopathologic study of 50 autopsy cases of idiopathic pulmonary fibrosis and
      non-diffuse usual interstitial pneumonia].
AB  - We investigated 50 autopsy cases of idiopathic pulmonary fibrosis (IPF) and non
      diffuse usual interstitial pneumonia (UIP), and subgrouped them into three
      subtypes based on morphologic differences in the fibrosis (honeycomb): typical
      thick-walled honeycomb type (16 cases), atypical thin-walled honeycomb type (27
      cases) and atelectatic indurated type (6 cases), with one undetermined case. In
      the thin-walled type, the percentage of males (93%), the percentage of smokers
      (89%), and the percentage of lung cancer cases (52%) were significantly higher
      than in the other two subtypes (p < 0.02, p < 0.001 and p < 0.05, respectively).
      However, in the thick-walled and indurated types there were significantly higher
      percentages of DAD (38% and 67%, respectively) than in the thin-walled type (15%)
      (P < 0.05). Accordingly, each subtype was thought to be closely related to its
      IPF clinical features, and showed differences in the development of acute
      exacerbation and lung cancer. This study proposes the existence of a UIP subset
      and suggests that this subgrouping can help in the management of the disease.

PMID- 16285588
TI  - [Changes in sleep architecture by resumption of CPAP in patients with sleep apnea
      syndrome].
AB  - It is known that application of continuous positive airway pressure (CPAP)
      improves sleep architecture in patients with sleep apnea syndrome (SAS). In
      contrast, there have been only a few studies which deal with deterioration of
      sleep architecture by discontinuation of CPAP. In the present study we analyzed
      changes of sleep architecture by temporary removal of CPAP. The subjects were 41
      patients who underwent polysomnography (PSG) for diagnosis of SAS. The patients
      chose either a 1-night study in which only PSG was done, or a 2-night study in
      which, after treatment with CPAP for one month, PSGs with and without CPAP at
      night were done. The mean ages, heights, and weights between the 1-night group
      and the 2-night group were not statistically different The mean AHI of the 1
      night group (38.9 +/- 5.0/hr; mean +/- SE) and that of the 2-night group (45.7 +/
      5.4/hr) were not significantly different. The mean AHI profoundly decreased (4.4
      +/- 0.9) by CPAP therapy on the second night. Percents of each sleep stage in the
      1-night group were as follows; stage 1, 31.8%; stage 2, 50.0%; stage (3 + 4),
      2.8%: REM, 15.7%. In the 2-night group, stage 1 was 43.6%, significantly higher
      than that in the 1-night group, while stage 2 was 39.9%, which was significantly
      smaller. There were no significant difference in stage (3 + 4) and REM. When CPAP
      was again applied to the 2-night patients, stage 1 significantly decreased to
      15.5%, while stage 2 (55.6%), stage (3 + 4) 6.7%, and REM (22.3%) increased
      significantly. Therefore, cessation of CPAP shifts the sleep stage from stage 2
      to stage 1. Since stages 1 and 2 occupy approximately 80% of total sleep
      duration, the shift may have some physiological significance. Resumation of CPAP
      may have improved quality of life and day-time sleepiness by decreasing stage 1
      sleep and increasing stages of deeper sleep and REM.

PMID- 16285589
TI  - [Three cases of transcatheter embolization for pulmonary arteriovenous fistula
      using detachable coils].
AB  - We report three cases of transcatheter embolization for pulmonary arteriovenous
      fistula (PAVF) using Interlocking detachable coils (IDC) and detachable fibered
      coils (DFC), and evaluate the outcome of transcatheter embolization with
      reference to previous reports. The three patients were women aged 56, 70 and 71
      years. They had no symptoms, but chest radiographs were abnormal. None of them
      had Rendu-Osler-Weber disease. The three PAVFs were of the simple type, with a
      single feeding vessel and a single draining vein. In case 1, the feeding vessel
      arose from the left A4, while the feeding vessels in case 2 and 3 arose from the
      left A5. In case 1, we embolized the venous sac with detachable coils because the
      feeding vessel was short and kinked. In case 2 and 3, we embolized the feeding
      vessels closer as to the neck of the venous sac using detachable coils. The three
      PAVFs were all successfully embolized without severe complications, and
      transcatheter embolization seems to be an effective therapy.

PMID- 16285590
TI  - [Serum amyloid protein A was a useful marker for steroid tapering in a case of
      MPO-ANCA-associated vasculitis].
AB  - A 55-year-old man was admitted complaining of hemosputa, fever and dyspnea. The
      chest radiographs and computed tomography showed a diffuse alveolar filling
      pattern; suggesting alveolar hemorrhage. Laboratory data demonstrated renal
      dysfunction with hematuria and proteinuria and serum MPO-ANCA was also elevated.
      Respiratory failure progressed rapidly within two days. Steroid pulse therapy and
      plasmapheresis was performed. Thereafter, symptoms and chest radiograph findings
      improved dramatically. However proteinuria persisted as steroid administration
      was tapered. Renal biopsy demonstrated gromeluronephritis and interstitial
      lymphocyte infiltration. After administering a second course of steroid semi
      pulse therapy, her proteinuria improved. C-reactive protein and MPO-ANCA
      decreased to normal levels after the initial steroid therapy, but serum amyloid A
      protein (SAA) gradually elevated. The second course of steroid pulse therapy
      normalized SAA, and proteinuria improved. Based on these findings, SAA seems to
      be a more sensitive marker for steroid tapering than either CRP or MPO-ANCA.

PMID- 16285591
TI  - [A case of pulmonary epithelioid hemangioendothelioma detected on medical
      checkup].
AB  - A 51-year-old woman was admitted to our hospital because of bilateral multiple
      nodular shadows detected on a medical checkup chest X-ray film. Video-assisted
      thoracoscopic biopsy and hematoxylin eosin staining showed protrusion of the
      polypoid tumor tissue into the alveolar lumina, and the centers of nodules were
      occupied by hyalinized matrices. Immunohistochemical stain demonstrated that
      tumor cells were positive for factor VIII-related antigen, CD-34, and vimentin.
      The tumor was therefore diagnosed as pulmonary epithelioid hemangioendothelioma
      (PEH). PEH usually grows slowly. Standard therapy for PEH has not yet been
      established. We have followed the patient for 2 years without any treatment, but
      no symptoms have appeared.

PMID- 16285592
TI  - [A case of drug-induced pneumonia possibly associated with simvastatin].
AB  - A 59-year-old woman was admitted because of general fatigue, cough and
      progressive dyspnea about 5 months after treatment with simvastatin for
      hyperlipidemia. A chest radiograph and computed tomography scans revealed ground
      glass and reticular opacities in the right middle and lower lung fields. The
      percentage of peripheral blood eosinophils was elevated. After simvastatin was
      discontinued and administration of prednisolone was started, eosinophilia and
      reticular shadows improved. Drug lymphocyte stimulation test (DLST) for
      simvastatin was positive, so we diagnosed drug induced eosinophilic pneumonia.
      Now hyperlipidemia is treated frequently with HMG-CoA reductase inhibitor, but
      there are few reports demonstrating lung injury by this drug. We should be aware
      of lung side effects of HMG-CoA reductase inhibitor.

PMID- 16285593
TI  - [A case of cystic bronchial typical carcinoid].
AB  - A 53-year-old man was admitted with a nodular lesion on chest radiograph. Chest
      CT scan showed a cystic nodule in right S4 which gradually enlarged during follow
      up without therapy. Two years after the first examination, we performed middle
      lobectomy using video assisted thoracoscopy. Histologically, the tumor was found
      to be typical carcinoid by immunostaining.

PMID- 16285594
TI  - [A case of intratracheal osteoma].
AB  - A 75-year-old woman who complained of cough at night and stridor on exertion was
      admitted for examination of a possible tracheal tumor. Chest radiography and CT
      showed an intratracheal calcification. Bronchoscopic examination revealed a
      lobulated tumor on the anterior wall of the trachea, 6 cm below the vocal cord.
      The tumor was covered with tracheal epithelium. Microscopic findings of the
      transtracheal biopsy specimen revealed the tumor to be composed of bone tissues
      covered with normal tracheal epithelium. No cartilage, smooth muscle, or fats
      tissue were detected, and so a diagnosis of intratracheal osteoma was made. After
      Nd-YAG laser therapy, the size of the tumor decreased, and clinical findings
      improved. During periodical follow up after discharge, the residual tumor was
      expectorated at home on coughing. Histological examination confirmed the tumor to
      be osteoma. An intratracheal osteoma is very rare, and this case is the first
      case reported in Japan.

PMID- 16285595
TI  - [A case of desmoid tumor involving the posterior mediastinum].
AB  - A 36-year-old woman visited our department because of back pain. Chest CT showed
      the 35 x 20 mm mass to be located in the left posterior mediastinum. Neurogenic
      tumor or pulmonary sequestration was suspected. We followed the tumor for 2
      years, chest CT revealed an increase in size. En bloc resection of the tumor was
      performed. The tumor originated in the posterior mediastinum, protruded into the
      thoracic cavity and adhered to the left lower lobe and invaded the diaphragm,
      measuring 65 x 50 x 25 mm in size. This tumor was diagnosed pathologically as
      desmoid tumor which showed proliferation of spindle shape cells with collagen
      fibers, but with no cytologic atypia or mitotic figures were present. The tumor
      was alpha smooth muscle actin-positive, vimentin-positive, CD34-negative. Desmoid
      tumor of the posterior mediastinum is very rare. Desmoid tumors grow
      infiltratively and the recurrence rate after operation is high. Therefore, long
      term follow up will be necessary in this case, although the patient has been well
      for 10 months.

PMID- 16285596
TI  - [Video assisted thoracic surgery for Mycobacterium avium complex pulmonary
      disease spread over multiple pulmonary lobe within one lung].
AB  - A 75-year-old woman with Mycobacterium avium complex (MAC) pulmonary disease who
      had been treated by drug therapy for 7 years was admitted on an emergency basis
      for hemoptysis. Through the previous 7 years, her sputum cultures had been
      positive for MAC, and her clinical symptoms and examinations, such as chest X-ray
      and computed tomography, revealed that her condition had worsened. The lesions
      spread over the right middle lobe, segment 3 (S3) in the right upper lobe, and
      segment 6 (S6) in the right lower lobe, however, no lesions were present in the
      left lung. Since we believed that the disease was localized unilaterally,
      surgical treatment was selected. The surgical procedures that were employed
      included right middle lobectomy, right S3 segmentectomy and partial resection of
      right S6 by thoracoscopy. Sixteen months postoperatively, the sputum culture is
      negative for MAC. Our procedure enabled the preservation of effective lung
      function and was successful in controlling MAC pulmonary disease. It is believed
      that surgery for MAC pulmonary disease should be evaluated in more patients to
      decide the appropriate surgical indication and procedure.

PMID- 16285597
TI  - [A case of malignant lymphoma diagnosed by thoracoscopy with local anesthesia].
AB  - A 67-year-old woman was hospitalized with right pleural effusion on chest
      radiography. Chest CT showed a thickened parietal pleura and pleural effusion in
      the right thorax. Cytological examination of pleural effusion showed atypical
      plasma cells. We performed thoracoscopy with local anesthesia for diagnosis and
      observed an about 5 x 5 cm seized red soft tumor on the parietal pleura.
      Pathological and immunohistochemical examination of the pleural tumor revealed
      that it was marginal zone B-cell malignant lymphoma. In this case, we could not
      reach a diagnosis only by cytological examination of the pleural effusion.
      Thoracoscopy with local anesthesia was safe and useful for diagnosis of malignant
      lymphoma with pleural effusion. Most cases of primary pleural malignant lymphoma
      have a history of chronic pyothorax. This case is thought to be a very rare case
      of primary pleural malignant lymphoma with no history of pyothorax.

PMID- 16285598
TI  - Effect of time interval between bleaching and bonding on tag formation.
AB  - The objective of this study was to assess penetration of adhesive material in
      enamel bleached with 35% hydrogen peroxide using optical polarized light
      microscopy. Extracted human teeth were randomly assigned to 5 groups, each
      representing a specific time interval between bleaching and the application of an
      adhesive material. They were designated as: (TC) the control group-restorations
      in unbleached teeth; (T0) comprising restorations carried out immediately after
      bleaching; (T7) comprising restorations 7 days after bleaching; (T14) comprising
      restorations 14 days after bleaching; and (T21) comprising restorations 21 days
      after bleaching. Length of resin tags was measured with an Axiophot
      photomicroscope at a x 400 magnification, and the results subjected to an ANOVA
      for a comparison between groups, with a p value of < 0.05. Differences between
      the groups were verified using a Tukey test at a confidence level of 5%. The
      specimens in the control group (TC) and experimental groups T7, T14 and T21
      showed better penetration of adhesive material into enamel in comparison with
      experimental group T0. This suggests that a gap of at least 7 days should be left
      between bleaching enamel with 35% hydrogen peroxide and placing adhesive bonding
      agents and undertaking resin composite restoration work.

PMID- 16285599
TI  - Relationship between large tubules and dentin caries in human deciduous tooth.
AB  - The purpose of this study was to elucidate the relationship between large tubules
      and dentin caries by using human deciduous incisors that showed various levels of
      attrition but no macroscopical lesions resulting from caries. The teeth were cut
      longitudinally in the mesio-distal direction and the exposed surfaces observed
      with a high-resolution field emission scanning electron microscope. The inside of
      each large tubule showed dense collagen fibers running parallel to its long axis
      and small spherical bodies of aggregated crystals, but no marked attrition. In
      teeth where attrition had exposed dentin at the incisal edge, oral bacteria had
      infiltrated the large tubules. Furthermore, in teeth with advanced attrition, it
      was difficult to distinguish between the large tubules and the surrounding dentin
      matrix, and numerous bacteria were observed in both areas. These findings support
      the hypothesis that large tubules play a role in the pathway of caries formation
      in coronal dentin when incisal dentin is exposed by attrition. This suggests that
      early treatment of exposed dentin surfaces might be effective in preventing
      dental caries.

PMID- 16285600
TI  - Loss of heterozygosity and microsatellite instability on chromosome 2q in human
      oral squamous cell carcinoma.
AB  - Allelic imbalance or loss of heterozygosity (LOH) and microsatellite instability
      (MSI) have been used to identify regions on chromosomes that may contain putative
      tumor suppressor genes. To obtain a detailed understanding of genetic alterations
      in oral cancer, 10 highly polymorphic markers mapped on chromosome 2 were used to
      examine 25 cases of oral squamous cell carcinoma (SCC). With these, we analyzed
      chromosome 2q for LOH in 25 primary oral SCCs and constructed a deletion map for
      this arm of the chromosome. LOH was detected in 16 (64%) of the 25 informative
      samples at one or more of the loci examined. MSI was observed in 5 (20%) of the
      25 cases. Among the loci examined, LOHs were restricted to D2S1328 and D2S206 on
      chromosomes 2q14-21 and 2q36, respectively, with the former locus showing a rate
      of 5 (20.8%) and the latter a rate of 6 (25%) of the 24 informative cases. These
      observations taken in conjunction with data from 40 former cases analyzed at our
      laboratory suggest that the high incidence of LOH at chromosome 2q is associated
      with carcinogenesis of oral SCC. The regions that comprise the D2S1328 and D2S206
      loci may play an important role in the development of oral SCC, perhaps
      containing sites that harbor a putative tumor suppressor gene.

PMID- 16285601
TI  - Effects of autoclaving on dimensional qualities and physical properties (flexural
      rigidity and brittleness) of newly developed root canal filling point made of
      polypropylene (FLEX POINT NEO).
AB  - In this study, we investigated the effects of 10 cycles of conventional
      autoclaving (121 degrees C, 20 min) on the dimensional integrity and physical
      properties (flexural rigidity and brittleness) of a newly developed root canal
      filling point made of polypropylene (FLEX POINT NEO). We measured the diameters
      of autoclave-sterilized and non-treated polypropylene points (020 through 070)
      and calculated the incidence of deviation from ISO specifications (6877.4.4.1,
      1995). In order to ascertain physical properties, we tested autoclave-sterilized
      and non-treated polypropylene points (030, 050 and 070) for flexural rigidity.
      This was done by evaluating deflection value when a load was placed at the free
      tip-end of the point and brittleness in accordance with ISO specifications
      (6877.6.5.2). Ten cycles of autoclaving showed no significant effect on the
      diameters of the polypropylene points. All the polypropylene points in both the
      non-treated and the autoclave-sterilized groups met ISO specifications in terms
      of dimensional integrity of diameter. In the autoclave-sterilized group, 030 and
      050 polypropylene points showed a slight decrease in flexural rigidity (3.4% in
      030, 10.0% in 050). In terms of brittleness, none of polypropylene points showed
      any sign of fracture.

PMID- 16285602
TI  - Leukemia case in patient with taste dysfunction.
AB  - A blood examination was carried out in order to assess the serum zinc level in a
      patient with taste dysfunction. A blood cell count was also performed
      simultaneously and promyelocytic leukemia was identified. This case provides an
      example of leukemia being detected at the time of a blood test being given to
      assess taste dysfunction.

PMID- 16285603
TI  - Peripheral neuropathy due to thiamine deficiency after inappropriate diet and
      total gastrectomy.
AB  - Peripheral polyneuropathy due to vitamin B1 deficiency was encountered after
      total gastrectomy for gastric signet cell carcinoma in a patient with a history
      of breast-conserving surgery for breast cancer. She had greatly reduced her
      intake of animal foods, believing that would be effective for the prevention of
      re-occurrence of cancer. Her daily intake of vitamin B1 was less than half of the
      usual daily requirement. Patients with malignancy tend to adopt unusual diets,
      and proper advice about food intake is important for such patients, especially
      those with gastrectomy.

PMID- 16285604
TI  - Clinical profile and prognosis of hospitalized patients with congestive heart
      failure in Isehara, Japan.
AB  - Since the clinical profile and prognosis of heart failure depending on time of
      the study performed, regional characteristics of background population and
      different race, we attempted to evaluate the prognosis of symptoms and life
      expectancy of Japanese patients with heart failure. We evaluated the clinical
      profiles and prognoses of 1,015 consecutive patients with congestive heart
      failure (CHF) for whom hospitalization was required. A total of 1,015 consecutive
      CHF patients (584 males and 431 females) were enrolled in this study, however the
      total number of events investigated was 1,409. Of these patients, survival was
      confirmed in 413 patients, death was confirmed in 299 patients, and the prognoses
      of 303 patients remained unknown due to transfer to other hospitals or for some
      other reasons. The mean age on admission was 68.4 +/- 14.9 years. In both males
      and females, the peak age at the onset of CHF was in the seventies, and for
      patients in their eighties, the number of female patients with CHF was larger
      than that of male patients. Major underlying heart diseases consisted of ischemic
      heart disease (34%), valvular heart disease (22%), dilated cardiomyopathy (11%),
      and hypertension (10%). Most CHF patients who had dilated cardiomyopathy as an
      underlying disease were hospitalized several times, and 45% of them were
      hospitalized 3 times or more. The life expectancy of patients with CHF caused by
      ischemic heart disease was the poorest, and their 5-year and 10-year survival
      rates were 55% and 38%, respectively. Similarly, 5-year and 10-year survival
      rates of patients with CHF caused by valvular heart disease, hypertension, and
      dilated cardiomyopathy were 62% and 44%, 58% and 53%, and 70% and 65%,
      respectively. In 299 deceased patients, the mean age at death was 72.2 +/- 13.9
      years. In all these deceased patients, direct causes of death were sudden death
      (16.1%), CHF (42.2%), others (31.4%), and unknown (10.4%). The frequency of
      sudden death was highest (25%) in patients with CHF caused by dilated
      cardiomyopathy, followed by those with CHF caused by valvular heart disease (18%)
      and those with CHF caused by ischemic heart disease (17.5%). In addition, the
      frequency of death from CHF was highest (60%) in those with CHF caused by dilated
      cardiomyopathy, followed by those with CHF caused by ischemic heart disease
      (49.2%).

PMID- 16285605
TI  - A case of familial hypercholesterolemia; secession from LDL-apheresis by the drug
      treatment with potent statin and resin.
AB  - Low density lipoprotein (LDL)-apheresis is a useful tool for the treatment of
      familial hypercholesterolemia (FH) with coronary artery disease (CAD). However,
      it gives economic, physical and mental burdens for the patients. We reports a
      case of FH in whom LDL-apheresis treatment was seceded with drug treatment with a
      potent statin and bile acid-sequestering resin. A 54-year-old woman was admitted
      for evaluation of atherosclerotic lesion after 4 years of LDL-apheresis and 1
      year of drug medication with a potent statin, atorvastatin and resin,
      cholestimide with coronary angiography. She had been diagnosed as heterozygous FH
      when she was 46 years old. Oral medication was initiated at the outpatient
      clinic. LDL-cholesterol (C) level was not successfully controlled despite the
      administration of a statin, pravastatin, a fibrate, clinofibrate and probucol at
      maximum doses Concomitantly. Therefore, as combination therapy, LDL-apheresis was
      introduced in May 1997. However, the patient strongly complained of the economic,
      physical, and mental burdens of LDL-apheresis and requested discontinuation of
      apheresis. Therefore, LDL-apheresis was discontinued in July 2000, and oral
      medication was subsequently changed to a combination of atorvastatin and
      cholestimide, resulting in successful control of serum LDL-C level by oral
      medication alone. We compared coronary arteriographic findings between 1997 and
      2001. No advancement of lesions was observed. We think that strong drug treatment
      can secede from the LDL-apheresis for treatment of patients with FH.

PMID- 16285606
TI  - The threshold of the intermittent hypoxic exposure period to elicit polycythemia
      in rats.
AB  - It is not yet clear whether there is an intermittent hypoxia (IHx) threshold to
      elicit polycythemia and blood pressure elevation, and whether blood hemoglobin
      concentration ([Hb]) increases with an increase in the hypoxic exposure period.
      We have previously shown that repetitive exposure to 10% O2 for 60 min/day for up
      to 5 weeks does not produce polycythemia. In the present study, we evaluated the
      effect of IHx of 10% O2, 120 min/day for 1, 2, 3 and 4 weeks on [Hb], arterial
      blood pressure, heart rate and arterial blood gases in the rat. IHx of 10% O2,
      120 min/day induced polycythemia at 1 week and produced a time-dependent increase
      in [Hb] from 0 week to 4 weeks. Arterial blood pressure significantly increased
      during IHx exposure for 4 weeks probably due to a combination of an increased
      sympathetic activity as well as increased blood viscosity. The IHx threshold for
      polycythemia might exist between 60 min/day and 120 min/day in this level of
      hypoxia.

PMID- 16285607
TI  - The behavior of thoracic trabecular bone during flexion.
AB  - Thoracic compression fractures are often described as anterior wedge fractures.
      Although the radiographic signs of these fractures are easily identified, the
      mechanism of the trabecular failure is not well understood. The current study
      addressed this mechanism in the lower thoracic spine by measuring the trabecular
      strain. Trabecular strain was measured in six human thoracic cadaver spines
      during 1) compressive and 2) flexural loading. The strains were measured at
      incremental loads using a texture correlation. They were analyzed by global
      contour plots and regional analysis of the T11 vertebrae. Specimens loaded under
      only compression exhibited uniform strains in the vertebral body. During flexion,
      however, the strains were concentrated in the anterosuperior margin of the
      vertebral body and the compressive and shear strain magnitudes in this region
      were significantly increased. These results demonstrate that the flexural
      position places the lower thoracic spine at greater risk of anterior compression
      fracture as seen clinically.

PMID- 16285608
TI  - Increase in plasma malondialdehyde-modified low-density lipoprotein in patients
      with atherothrombotic cerebral infarction.
AB  - Oxidized low-density lipoprotein cholesterol (Ox-LDL) is considered to play a
      critical role in the pathogenesis of atherosclerosis. We investigated the role of
      malondialdehyde-modified LDL (MDA-LDL), an indicator of Ox-LDL, in cerebral
      infarction. We also investigated the relationship between MDA-LDL and
      atherosclerotic change of the carotid artery. Subjects were 30 patients with
      lacunar infarction (LA), 19 patients with atherothrombotic infarction (AT) and 48
      controls. Carotid arteries were evaluated with B-mode Doppler ultrasonography.
      The intima-media thickness (IMT) was considered to be increased if its value was
      more than 1.1 mm. The level of MDA-LDL concentration was significantly (P < 0.05)
      elevated in AT patients (129.96 +/- 27.88 U/I) than in LA patients (99.35 +/-
      34.06 U/l) and controls (97.65 +/- 32.61 U/l). Among AT patients, plasma level of
      MDA-LDL concentration was statistically significantly elevated in the group with
      increased IMT (139.7 +/- 24.5 U/l) than in the group without increased IMT (102.7
      +/- 17.2 U/l). No statistically significant difference was found among LA
      patients. However, there was no difference in LDL-C concentration between the
      patients with and without IMT thickening among LA or AT patients. The
      concentration of MDA-LDL was significantly decreased (P < 0.05) after statin
      administration for 5-6 months. MDA-LDL, namely degraded or qualitatively changed
      LDL-C, appears to be related to atherosclerotic change of the carotid artery in
      AT patients.

PMID- 16285609
TI  - Expression of carbohydrate antigens (SSEA-1, sialyl-Lewis X, DU-PAN-2 and CA19-9)
      and E-selectin in urothelial carcinoma of the renal pelvis, ureter, and urinary
      bladder.
AB  - Carbohydrate antigens and E-selectin play important roles in the invasion and
      metastasis of cancers. We examined the expression of these antigens and their
      ligand protein, E-selectin, in urothelial carcinomas to evaluate whether their
      staining is correlated with the grade and stage of cancer. We studied the
      expression of carbohydrate antigens (type 1 and type 2 blood-group antigens) and
      E-selectin in urothelial carcinomas of the renal pelvis, ureter, and urinary
      bladder in 52 patients by staining SSEA-1 (LeX), sialyl LeX (sLeX), DU-PAN-2,
      CA19-9, and E-selectin with 5 different monoclonal antibodies (MAbs) to evaluate
      whether their staining correlated with cancer grade and stage. The differences
      between organs with regard to the degree of expression of these antigens were not
      evident. Type 2 antigens (SSEA-1 and sialyl LeX) are frequently expressed in the
      tumor cells regardless of atypical grade. The expression level of type 1 antigens
      (DU-PAN-2 and CA19-9) is lower than that of type 2 antigens. However, the
      presence of DU-PAN-2 tends to correlate with the grade of atypia; however, that
      of CA19-9 is inversely proportional to the grade of atypia. The lack of CA19-9
      and appearance of DU-PAN-2 in urothelial carcinoma implies a high malignant
      potential. The expression of E-selectin can be correlated with stage and grade of
      tumor atypia. Type 2 antigen and E-selectin may be involved in tumor invasion and
      metastasis.

PMID- 16285610
TI  - Video-assisted thoracoscopic surgery under local anesthesia for right empyema
      secondary to aspiration pneumonia caused by esophageal achalasia: case report.
AB  - A 55-year-old man was admitted to the Department of Internal Medicine of our
      hospital with chief complaints of fever, cough, and right-sided chest pain. Plain
      radiography of the chest revealed widening of the mediastinum (attributed to
      esophageal achalasia), pneumonia, and right pleural effusion. According to the
      properties of the pleural fluid, empyema was diagnosed. Because the empyema was
      resistant to antibiotic treatment and was in the fibrinopurulent stage, it could
      not be drained effectively. Therefore, after treatment of the esophageal
      achalasia by balloon dilatation of the lower esophagus, the empyema was treated
      by video-assisted thoracoscopic surgery, i.e., by video-assisted thoracoscopic
      drainage and curettage of the empyema cavity, under local anesthesia.

PMID- 16285611
TI  - Eosinophilic pleurisy induced by dantrolene.
AB  - A 70-year-old male developed eosinophilic pleurisy fifteen years after dantrolene
      sodium had been started for his spastic paraplegia due to spinocerebellar
      degeneration. Drug lymphocyte stimulation test (DLST) for dantrolene was
      positive. After discontinuance of dantrolene, pleural effusion gradually
      decreased and inflammatory reaction improved. During two-year observation, we
      have found no relapse of pleurisy without special medication. We present this
      case and compare this case with other 10 reported cases.

PMID- 16285612
TI  - [Relationship between pollen allergy and oral allergy syndrome].
AB  - We recently evaluated the relationship between pollen allergy and oral and
      pharyngeal hypersensitivity to fruits and vegetables (oral allergy syndrome) over
      8 years (1995 approximately 2002) in Sapporo. 1. Of 843 patients with birch
      pollen (BP) allergy (CAP score 2 or more), 378 patients (37%) had episodes of
      oral allergy syndrome (OAS), and the rate in BP allergy was higher than in other
      allergies. 2. In patients with BP allergy, the most frequent foods causing OAS
      were apple, peach and cherry, followed by kiwi, pear, plum and melon. BP allergy
      patients demonstrated much more OAS with these foods than the patients without BP
      allergy. The higher the CAP score of BP, the higher the incidence of OAS to these
      foods was found to be. In patients with OAS and BP allergy, the higher the CAP
      score of BP, the higher the number of foods causing OAS was found to be. 3. In
      patients with BP allergy, a multiple logistic regression analysis was performed
      to identify factors affecting the rate of OAS. Positive factors were a high BP
      CAP score and being female. A negative factor was mite CAP positive. Furthermore,
      mugwort pollen (MP) CAP positive patients had much more OAS to kiwi and tomato
      than MP CAP negative patients.

PMID- 16285613
TI  - [Concurrent chemoradiotherapy for advanced hypopharyngeal cancer].
AB  - INTRODUCTION: Chemotherapy has been shown to be most effective when delivered
      concurrently with radiation for the patients with advanced stage tumors. We
      conducted a concurrent chemoradiation using systemic infusion of cisplatin (CDDP)
      and 5-fluorouracil (5-FU). PATIENTS AND METHODS: Thirty-nine patients with
      advanced hypopharyngeal cancer received one or two cycles of intravenous
      administration of CDDP (80-100 mg/m2) followed by 120-hour continuous infusion of
      5-FU (800-1000 mg/m2), and concomitant radiotherapy (200 cGy/day x 20-35
      fractions) during the period from December, 1993 through December, 2001. Three of
      them were in stage III, 31 in stage IVA, and 5 in stage IVB. Until 1999
      definitive surgery was planed in almost all the patients, however, primary tumors
      had pathologically disappeared in eleven out of the 20 (55%) of the surgical
      specimens. Based on the result, definitive surgery was reserved for residual or
      recurrent tumors afterwards. RESULTS: The complete response (CR) rates according
      to the T factor were 100% (1/1) for T1, 86% (6/7) for T2, 67% (2/3) for T3, and
      50% (14/28) for T4, respectively. Two cycles of chemotherapy yielded a
      significantly higher CR rate than that of one cycle (P = 0.0371). One patient
      died of aspiration pneumonia. The rate of grade 3-4 leukocytopenia was 38%. The
      projected 5-year disease specific and overall survival rates were 57 and 51%,
      respectively. CONCLUSIONS: Concurrent chemoradiotherapy is promising as far as
      improving survival as well as organ preservation.

PMID- 16285614
TI  - [Safety and usefulness of the long-term intranasal topical treatment with
      steroids for olfactory dysfunction].
AB  - Intranasal topical steroids are commonly used for the treatment of olfactory
      dysfunction. Although the side effects are considered to be minimal, these have
      not been studied in detail. We examined the side effects of intranasal topical
      treatment with steroids in patients with olfactory dysfunction. We treated 62
      patients with intranasal topical application of 0.1% betamethasone sodium
      phosphate (Rinderone) administered to the olfactory clefts. After treatment for 1
      or 2 months, serum ACTH or cortisol was reduced in 42 (68% of total) patients,
      however, no clinical symptoms associated with steroid side effects were observed.
      The treatment was discontinued in 8 of these patients, who elected to withdraw
      from the treatment. In these patients, the serum ACTH or cortisol returned to
      normal a month after stopping the treatment. In the remaining 34 patients, the
      topical treatment was continued and in only 4 of these patients, minor steroid
      associated side effects such as the sensation of facial swelling and facial hair
      thickening, appeared 2-5 months after beginning the treatment. These side effects
      disappeared within a month after stopping the treatment. Regarding the
      therapeutic efficacy, in 18 (78%) of the 23 patients who continued treatment for
      an average period of 5 months, steroid treatment significantly improved their
      olfactory dysfunction. In conclusion, although it is important to consider the
      potential side effects of long-term intranasal topical treatment with steroids
      for olfactory dysfunction, this treatment is a highly effective method against
      olfactory dysfunction with minimal side effects.

PMID- 16285615
TI  - [Clinical analysis of cervical metastatis from an unknown primary carcinoma].
AB  - From 1997 to 2004, 19 cases-18 men and 1 woman-with cervical lymph node
      metastasis from an unknown primary carcinoma were retrospectively investigated
      regarding the clinical observation and the treatment outcome. With respect to the
      histopathological types, 16 cases had squamous cell carcinoma, 2 cases had
      adenocarcinoma and 1 case had ductal carcinoma. As for the region of lymph node
      metastasis with maximum size, metastasis located in the upper deep cervical
      region arrounted for 84%. The presence of primary lesions was comfirmed in 11
      cases (3 tonsil, 1 nasopharynx, 1 base of tongue, 2 hypopharynx, 1 esophagus, 1
      larynx, 1 gallduct, 1 mammary gland) after the treatment of their metastatic
      leisions. Tonsillectomy and Blind biopsy were effective for 5 patients. Seventeen
      patients were treated with neck dissection. Eleven patients with neck dissection
      underwent radiotherapy. The overall 3-year survival rate as determined by the
      Kaplan-Meier method was 62%. The 3-year survival rate of the 17 cases whose
      metastatic leisions were treated with radical neck dissection was 66%. The 3-year
      survival rate of cases with known primary sites and cases with unknown primary
      sites after treatment were 55% and 83%, respectively. Radiotherapy with radical
      neck dissection was thought more effective than radical neck dissection for local
      and neck control.

PMID- 16285616
TI  - [Characteristics of prostatic cancer in men with a serum prostate-specific
      antigen level of < or =4.0 ng/ml].
AB  - Fifteen out of 140 men (median age 67 years, range 62-75) had a serum prostate
      specific antigen (PSA) level of < or = 4 ng/ml before radical prostatectomy which
      was performed without preoperative neoadjuvant hormonal therapy between 2001
      January and 2004 September. Demographic and clinical data were analyzed.
      Pathological specimens were evaluated by routine hematoxylin and eosine staining
      and immunohistochemistry with anti-PSA antibody, for both pathological staging
      and grading, and for the presence of PSA production. Pathological data were
      compared between patients with PSA < or = 4 ng/ml and those with 4 < PSA < or =
      10 ng/ml. Clinically insignificant cancer was defined as a cancer volume of < 0.5
      ml and the Gleason score < or = 6. The median PSA level was 3.0 ng/ml (range 1.4
      3.9). Thirteen tumors (87%) were pT2. One tumor had a Gleason score of 7 and 14
      tumors had a final Gleason score of < or = 6. Nine (60%) tumors were clinically
      insignificant. Comparison of pathological variables, PSA < or = 4 ng/ml cancer
      had a significantly lower Gleason score (p = 0.0029), and a smaller cancer volume
      (p = 0.0451) than 4 < PSA < or = 10 ng/ml cancer. All tumors were stained
      strongly for PSA. During a median follow-up of 24 (9-36) months, no patient
      showed elevated PSA (PSA > or = 0.1 ng/ml). Most prostate cancers in men with a
      PSA level of < or = 4 ng/ml were pT2, and about half of them were clinically
      insignificant. All cancers produced PSA.

PMID- 16285617
TI  - Transrectal high-intensity focused ultrasound in the treatment of localized
      prostate cancer: a multicenter study.
AB  - We report a multicenter trial with transrectal high-intensity focused ultrasound
      (HIFU) in the treatment of localized prostate cancer. A total of 72 consecutive
      patients with stage T1c-2NOM0 prostate cancer were treated using the Sonablate
      500TM HIFU device (Focus Surgery, Indianapolis, USA). Biochemical recurrence was
      defined according to the criteria recommended by the American Society for
      Therapeutic Radiology and Oncology Consensus Panel. The median age and prostate
      specific antigen (PSA) level were 72 years and 8.10 ng/ml, respectively. The
      median follow-up period for all patients was 14.0 months. Biochemical disease
      free survival rates in all patients at 1 and 2 years were 78% and 76%,
      respectively. Biochemical disease-free survival rates in patients with stage T1c,
      T2a and T2b groups at 2 years were 89, 67% and 40% (p = 0.0817). Biochemical
      disease-free survival rates in patients with Gleason scores of 2-4, 5-7 and 8-10
      at 2 years were 88, 72% and 80% (p = 0.6539). Biochemical disease-free survival
      rates in patients with serum PSA of less than 10 ng/ml and 10-20 ng/ml were 75%
      and 78% (p = 0.6152). No viable tumor cells were noted in 68% of patients by
      postoperative prostate needle biopsy. Prostatic volume was decreased from 24.2 ml
      to 14.0 ml at 6 months after HIFU (p < 0.01). No statistically significant
      differences were noted in International Prostate Symptom Score, maximum urinary
      flow rate and quality of life analysis with Functional Assessment of Cancer
      Therapy. HIFU therapy appears to be minimally invasive, efficacious and safe for
      patients with localized prostate cancer with pretreatment PSA levels less than 20
      ng/ml.

PMID- 16285618
TI  - [Successful subtotal parathyroidectomy for giant tumor calcinosis with secondary
      hyperparathyroidism].
AB  - A 54-year-old woman was referred to our hospital for the treatment of secondary
      hyperparathyroidism due to chronic renal failure. She was on hemodialysis for 7
      years and suffered from giant tumor calcinosis of the major joints associated
      with severe hypercalcemia and hyperphosphatemia. The largest one of the left hip
      joint caused gait disturbance. Medical therapy was unsuccessful and she underwent
      subtotal parathyroidectomy. After the operation, although the levels of serum
      calcium and phosphate were not normalized, the level of parathyroid hormone was
      lowered to the normal range. The volume of the tumor calcinosis gradually reduced
      and she became able to walk for a short distance 10 months after the operation.

PMID- 16285619
TI  - [Schwannoma of the kidney with severe calcification: a case report].
AB  - Schwannoma arising from the kidney is a rare benign tumor, with only 20 cases
      reported in the English literature. We encountered a histopathologically typical
      Schwannoma of the kidney in a 39-year-old woman, which was characterized by
      marked calcification. Radical nephrectomy was performed under the diagnosis of
      renal cell carcinoma. The 21 reported cases of schwannoma of the kidney,
      including the present case, are reviewed in detail.

PMID- 16285620
TI  - [A case of incomplete distal renal tubular acidosis undergoing repeated treatment
      by extracorporeal shock-wave lithotripay and transureteral lithotripsy for
      recurrent urolithiasis].
AB  - A 65-year-old woman was referred to our hospital for further examination of
      recurrent urinary stone formation. She had undergone 49 sessions of
      extracorporeal shock-wave lithotripay (ESWL) and 3 sessions of transureteral
      lithotripsy (TUL) under the diagnosis of idiopathic recurrent urolithiasis at
      another hospital. An excretory urography showed bilateral hydronephrosis and a
      retrograde urography revealed bilateral lower ureteral stricture. Ammonium
      chloride loading test demonstrated incomplete distal renal tubular acidosis.
      Potassium citrate therapy had begun and bilateral nephrostomies were required in
      order to prevent recurrent urinary tract infection and new stone formation.
      Literature was reviewed and discussion was made on the ureteral stricture after
      ESWL and TUL, and on incomplete distal renal tubular acidosis.

PMID- 16285621
TI  - [A case of sigmoid colon cancer that spread to the urinary bladder via the
      ureter].
AB  - A 69-year-old male was admitted to the hospital with the chief complaint of left
      hydronephrosis and diagnosed. A year ago, he underwent sidmoidectomy to cure
      sigmoid colon cancer diagnosed as stage IV. Ultrasonography (US) and computed
      tomography (CT) detected the compression of the ureter at its middle left due to
      the enlargement of the left iliac lymph node and hydronephrosis and hydroureter
      at the proximal to the compressed part. Then, a ureteral tumor was suspected and
      urinary cytology was class V. Cystoscopy detected a papillary tumor projecting
      from the left ureteral orifice. Because the histopathological manifestation by
      transurethral resection of bladder tumor and that by the sidmoidectomy were
      consistent, it was considered that sigmoid colon cancer spread to the urinary
      bladder via the left ureter. There have been only 4 reported cases of
      adenocarcinoma that multiplied in the ureter, and this is the fifth case report.

PMID- 16285622
TI  - [Augmentation ileocystoplasty in neurogenic bladder due to transverse myelitis in
      a woman with systemic lupus erythematosus].
AB  - A 39-year-old female with systemic lupus erythematosus (SLE) with a neurogenic
      bladder is described. She developed voiding disturbance with paraplegia and
      sensory disturbance on her inferior limb. Clinical findings suggested elevated
      activities of SLE with transverse myelitis. Although her symptoms were improved
      after one course of methylprednisolone pulse therapy, clean intermittent
      catheterization was required for urinary incontinence and residual urine. One
      year later, bilateral hydronephrosis and vesical diverticulitis developed, and
      thus augmentation ileocystoplasty was performed. After three months of the
      operation, hydronephrosis and urinary incontinence resolved with frequent clean
      intermittent catheterization. We should not overlook lower urinary tract symptoms
      in patients with SLE. We advocate performing a surgical procedure in cases in
      which conservative treatments are not effective.

PMID- 16285623
TI  - [Carcinoma in situ of the bladder involving the prostate with an unusual invasive
      pattern following BCG therapy: a case report].
AB  - We report a case of carcinoma in situ (CIS) of the bladder involving the prostate
      with an unusual invasive pattern following Bacillus Calmette Guerin (BCG)
      therapy. A 41-year-old man achieved complete response after a course of
      intravesical instillation of BCG for diffuse CIS of the bladder. Two years later,
      urine cytology became positive. We performed random biopsy of the bladder and
      urethra three times and examined the bilateral upper urinary tract with
      retrograde pyelography and split urine cytology. However, none of these
      examinations revealed any malignant features, leading to a suspicion that the
      prostate was the recurrent site. Transrectal needle biopsy of the prostate
      revealed urothelial carcinoma (UC) at the transition between bladder and
      prostate. Transurethral biopsy of the prostatic urethra also detected UC in a
      core of the bladder neck only. Under a diagnosis of UC involving the prostate, we
      performed total cystectomy with ileal conduit diversion. Histopathological
      findings of the surgical specimen showed prostatic stromal invasion of the tumor.
      In this case, CIS at the bladder neck might directly and silently invade the
      prostatic stroma, thus transurethral biopsy contributed little to the diganosis.
      We recommend transrectal needle biopsy of the prostate as well as TUR biopsy in
      such rare cases.

PMID- 16285624
TI  - A case of lupus cystitis diagnosed from urinary symptoms as the sole initial
      complaint.
AB  - Cystitis related with systemic lupus erythematosis (SLE) is termed as lupus
      cystitis. It is a subtype of SLE in which gastrointestinal and bladder symptoms
      are prominent and it usually manifests with other symptoms of SLE. We present a
      case in a 37-year-old woman whose sole complaint was the severe urinary symptoms.
      A biopsy of the bladder showed inflammation in the submucosa and the finding of
      vasculitis. An autoimmune disease was suspected from the blood serum sample. A
      further laboratory study was performed and she was diagnosed with SLE and lupus
      cystitis. Prompt therapy with corticosteroids resulted in the improvement of the
      severe bladder symptoms.

PMID- 16285625
TI  - [A case of synchronous double primary cancers of prostate, and bladder in a
      hemodialysis patient: a case report].
AB  - A 60-year-old male, who had been maintained on hemodialysis for 4 years, visited
      our hospital to receive living renal transplantation. He complained of
      macrohematuria, and preoperative examination showed elevation of psostate
      specific antigen (PSA). Cystoscopy revealed papillary tumors on the right lateral
      bladder wall. Transurethral resection of bladder tumor (TUR-Bt) was performed and
      histopathological examination showed transitional cell carcinoma, G2, pTa. The
      histologic diagnosis of the transrectal needle prostate biopsy specimen was
      moderately differentiated adenocarcinoma. Combined androgen blockade as a
      neoadjuvant therapy and radical prostatectomy were performed. A case of
      synchronous double primary cancers, comprised of adenocarcinoma of the prostate
      and transitional cell carcinoma of the urinary blader in a hemodialysis patient
      has never been previously reported in the Japanese literature.

PMID- 16285626
TI  - [A case report of bladder hernia associated with prostate cancer].
AB  - We report a case of bladder hernia. A 68-year-old man was admitted to our
      hospital for the management of prostate cancer. An egg-sized soft mass was
      palpated at his right inguinal region. Magnetic resonance imaging and cystography
      revealed that the mass was a bladder hernia. During radical prostatectomy, we had
      to resect the bladder hernia for safe regional lymphadenectomy. This hernia was
      the extraperitoneal type. The stage of prostate cancer was pT3b N0 M0. This is
      the third reported case of inguinal bladder hernia associated with prostate
      cancer in Japan.

PMID- 16285627
TI  - [Solitary genital leiomyoma of the tunica dartos: a case report and review of the
      literature in Japan].
AB  - We report a case of solitary genital leiomyoma arising from the tunica dartos of
      the scrotum. A 43-year-old man complained of a slightly tender left scrotal mass
      that had enlarged over approximately 17 years. On physical examination, the tumor
      was pedunculate and attached to the lower pole of the left scrotum. The tumor was
      clearly separate from scrotal contents such as the testis, epididymis, and
      spermatic cord. Ultrasonography showed the tumor to be 20.0 X 23.5 mm in
      diameter. Other laboratory examination findings were normal. Under local
      anesthesia, the tumor was resected at its base with overlying skin. On
      histopathological examination, the tumor consisted of interlacing bundles of
      smooth muscle cells, which were positive for vimentin, desmin, and a-actin. The
      tumor was diagnosed as leiomyoma arising from the scrotal tunica dartos. As
      solitary genital leiomyoma of the tunica dartos is rare, we have presented this
      case history and reviewed 23 cases that occurred in Japan.

PMID- 16285628
TI  - The teen years (whew!).

PMID- 16285629
TI  - An 11-month-old boy with Recurrent fever.

PMID- 16285630
TI  - An 11-day-old boy with lethargy, poor feeding, vomiting. Maple syrup urine
      disease.

PMID- 16285631
TI  - Puberty and adolescent sexuality.
AB  - Teenagers undergo biological, cognitive, and social changes. Each of these
      changes interacts with the other developmental parameters and may affect outcomes
      in late adolescence and adulthood. Sequence, tempo, and timing of puberty all
      affect when changes in hormones, feelings, and behavior will emerge in children.
      The pediatrician should recognize stages of pubertal development and be able to
      provide counseling and information to patients and parents. Some suggested
      resources are listed in the Sidebar.

PMID- 16285632
TI  - Sexual Development and behaviors of adolescents.
AB  - Adolescents are faced with many developmental tasks related to sexuality, such as
      forming romantic relationships and developing their sexual identities. Many
      adolescents will engage in a variety of sexual behaviors, including perhaps oral
      and anal sex, during this time period. Almost half will engage in vaginal sexual
      intercourse by the end of high school. A number of biological, psychosocial, and
      sociocultural factors can influence adolescents' romantic relationships and
      sexual behaviors. Some of these factors (eg, exposure to violence in the home,
      early pubertal development) may increase an adolescent's risk of being in an
      unhealthy relationship or engaging in sex at an early age. Parents, healthcare
      providers, and communities can support adolescents through these developmental
      tasks by forming close, connected relationships with teens and devising age
      appropriate messages about the development of healthy sexuality.

PMID- 16285633
TI  - Contraceptive behaviors in adolescents.
AB  - A wide range of factors influence adolescents' contraceptive behaviors, from
      personal characteristics to family context to social support to knowledge about
      and access to contraception. Improving knowledge about contraception and
      counseling about successful contraceptive use can be helpful in decreasing the
      remarkably high US rates of adolescent pregnancy. Encouraging the postponement of
      sexual activity until an individual adolescent is developmentally capable of
      participating in a mature, healthy, mutually respectful relationship that
      incorporates effective contraception clearly is a goal that most clinicians,
      parents, teachers, and other responsible adults can support. Contraceptive
      technologies that incorporate delivery systems that are "user-friendly" and long
      acting also will help to further lower US adolescent pregnancy rates that, while
      improving, are currently among the highest in the world.

PMID- 16285634
TI  - Sexually transmitted infections. Screening and diagnosis guidelines for primary
      care pediatricians.
AB  - Sexually transmitted infections are an important aspect of clinical care for
      adolescents. Recognition of common STI syndromes allows more efficient diagnosis
      and treatment. Prevention of infections by counseling, provision of condoms,
      periodic screening of at-risk teens, and treatment of partners all contribute to
      the sexual health of adolescent patients.

PMID- 16285635
TI  - Vaccines for sexually transmitted infections.
AB  - STIs are responsible for significant human suffering and carry significant
      economic costs. Strategies to control STIs, such as screening programs and
      condoms, have had limited success. Vaccines offer an additional method that is
      not coitally related and does not depend on consistent use. The HPV vaccine
      confers protection against the most common types causing cervical dysplasia.
      Mathematical modeling suggests that the HSV vaccine, given universally to all
      young women, should reduce genital and neonatal herpes in the population at
      large. Much work remains on vaccines for chlamydia and gonorrhea, but they offer
      the hope of preventing pelvic inflammatory disease and its sequelae. As these
      vaccines become licensed, their successful implementation will require the
      support of professional organizations, families, and providers.

PMID- 16285636
TI  - The power of words.

PMID- 16285637
TI  - 'House of hope'. Marrying medical research and patient care.

PMID- 16285638
TI  - Katrina's wake.

PMID- 16285640
TI  - Payback time. After last year's sluggish gains, hospital facilities professionals
      see healthy salary growth.

PMID- 16285639
TI  - Material matters. Developing guidelines for interior design finishes.

PMID- 16285641
TI  - Codes + standards. Gas guidance: ASSE provides help with gas system installation,
      maintenance and oversight.

PMID- 16285642
TI  - Environmental services. Carpet cure: a systematic approach to caring for carpets.

PMID- 16285643
TI  - [Liver diseases, vibrios and earth warming].

PMID- 16285644
TI  - [Inside-out application of ivermectin in scabies -- a hypothesis].

PMID- 16285645
TI  - The defect of the perforin granule system in cytotoxic T lymphocytes of atopic
      patients--are perforin reduction and hyperreleasability of clinical relevance?
AB  - Perforin-containing lytic granules are secretory lysosomes of cytotoxic
      lymphocytes. They act as a negative regulator of activated T cells, control
      immunoglobulin production, contribute to the regulation of the TH1/TH2 balance,
      and occupy a central role in anti-viral defense mechanisms. This review focuses
      on recent evidence for a fundamental defect in the lymphocytic perforin system of
      atopic patients, namely perforin reduction and the hyperreleasability of perforin
      granules. These findings are set in relation to the immune imbalance in atopy,
      which is characterized by a weakly restrained proliferation of allergen-specific
      T and B cells, a predominance of Ttype-2 cytokines, and an increased
      susceptibility to cutaneous infections. In the context of the wellknown defect of
      secretory lysosomes in mast cells and keratinocytes of atopic patients, the
      possibility of a cell type-independent major pathological factor in atopy is
      discussed: pan-cellular reduction and hyperreleasability of secretory lysosomes.

PMID- 16285646
TI  - [Extracorporeal photopheresis in progressive systemic sclerosis: discrimination
      of responders and non-responders].
AB  - BACKGROUND: The benefit of extracorporeal photopheresis (ExP) in progressive
      systemic sclerosis (PSS) is controversial. There is limited experience with the
      long-term use of ExP in PSS. The purpose of the present study was to distinguish
      between responders and non-responders by using ExP in PSS and to evaluate
      activation markers for PSS. PATIENTS AND METHODS: 20 subjects with PSS were
      treated for 12 months with ExP (interval: 1x/month) as an immunomodulating
      monotherapy (11/20) or combination therapy (9/20). The course of PSS was assessed
      by both specially designed clinical score and serological parameters (CRP, ANA,
      beta-galactosidase, P-III-P, CD4/CD8-ratio, TNF-alpha, 11-2-R, 11-6). RESULTS:
      After 12 cycles of ExP, 30% of the subjects showed a partial remission and 25%,
      stable disease (55% responders) while 45% had a progression (non-responders).
      Although there was no correlation between the clinical course and the serological
      parameters, an increase of beta-galactosidase during therapy marked a progression
      of PSS in non-responders. Responders with a short PSS-course before ExP, moderate
      ANA titres, normal TNF-alpha levels and lack of Scl-70 had a good prognosis.
      CONCLUSIONS: About the half of the subjects with PSS profited by the long-term
      use of ExP. Thereby the mild immunomodulating effect of ExP seems to be
      insufficient to control markedly progressive courses of PSS.

PMID- 16285647
TI  - Very low dose isotretinoin is effective in controlling seborrhea.
AB  - BACKGROUND: Excessive seborrhea, coarse-pored skin, minimal acne and oily scalp
      hair comprise a well-known clinical entity. It causes considerable concern, has
      social impact, and affects the quality of life in some individuals. Some patients
      seek treatment for seborrhea. No effective topical sebosuppressive medication is
      available. Oral isotretinoin is the only remedy for men. In women, oral
      isotretinoin is the most effective remedy, followed by antiandrogens. PATIENTS
      AND METHODS: Eleven patients in three groups were treated for 6 months with very
      low dose isotretinoin. The influence on seborrhea was measured during oral
      treatment with 5 mg/d, 2.5 mg/d, or 2.5 mg 3x weekly. RESULTS: Sebum production,
      measured with Sebutape, was reduced by up to 64%. Acne lesions regressed by as
      much as 84%. Follicular filaments were reduced by 66%. Microcomedones were
      reduced on average up to 86%. Quantitative bacteriology showed a reduction of
      Propionibacterium acnes but no increase of Staphylococcus epidermidis. Biopsies
      revealed a 51% reduction in sebaceous gland size. With Bentonite, a reduction of
      lipids was demonstrated with 2.5 and 5 mg isotretinoin/d but not with 2.5 mg 3x
      weekly. There was a shift within the lipid fractions: triglycerides dominated,
      followed by squalenes and free fatty acids. CONCLUSIONS: Good results were
      achieved in all patients. The small number of patients did not permit a
      statistical analysis of the three isotretinoin doses studied, but there was a
      tendency toward better results with the two higher doses.

PMID- 16285648
TI  - [Vibrio vulnificus sepsis].
AB  - A 59-year-old female patient with a history of malignant lymphoma presented with
      symptoms of septicaemia. The skin of the extremities showed bullous, necrotizing
      plaques. Blood culture revealed Vibrio vulnificus as the causative organism. The
      infection was most likely acquired while swimming in the unusually warm Baltic
      Sea through inadvertent swallowing of sea water. The disease is rare in Europe.
      It is discussed in view of its typical clinical and histological picture.

PMID- 16285649
TI  - [Temporary tattooing with henna induces contact allergy to textile dyes].
AB  - A woman developed widespread contact dermatitis after temporary tattooing with
      henna, caused by paraphenylenediamine (PPD) which had been added to the henna as
      an enhancer. The patient recovered after treatment; a week later an acute
      generalized rebound occurred after she wore dark clothing (black chador). Patch
      tests revealed type-IV allergy to PPD, along with multiple sensitisations to
      other textile dyes (disperse orange 3, para-aminoazobenzole, Bismark brown R).
      Temporary henna tattoos are not always harmless holiday souvenirs. The addition
      of color enhancers such as PPD into henna may lead to multiple contact allergies
      to other textile dyes.

PMID- 16285650
TI  - [Cutaneous T-cell lymphoma].

PMID- 16285651
TI  - [Multiple erythematous plaques with steady progression].

PMID- 16285652
TI  - [Recommendations for phototherapy and photochemotherapy].

PMID- 16285653
TI  - [Reader's letter on Norbert Haas, Andrea Wulff-Woesten,W. Sterry and H. Meffert.
      The treatment of psoriasis capillitii with dithranol. JDDG 2003, 1:688-693].

PMID- 16285654
TI  - [Reader's letter on Norbert Haas, Andrea Wulff-Woesten, W. Steary and H. Meffert.
      The treatment of psoriasis capillitii with dithranol. JDDG 2003; 1:688-693].

PMID- 16285655
TI  - Net analyte signal based statistical quality control.
AB  - Net analyte signal statistical quality control (NAS-SQC) is a new methodology to
      perform multivariate product quality monitoring based on the net analyte signal
      approach. The main advantage of NAS-SQC is that the systematic variation in the
      product due to the analyte (or property) of interest is separated from the
      remaining systematic variation due to all other compounds in the matrix. This
      enhances the ability to flag products out of statistical control. Using control
      charts, the analyte content, variation of other compounds, and residual variation
      can be monitored. As an example, NAS-SQC is used to appreciate the control
      content uniformity of a commercially available pharmaceutical tablet product
      measured with near-infrared spectroscopy. Using the NAS chart, the active
      pharmaceutical ingredient (API) content is easily monitored for new tablets.
      However, since quality is a multivariate property, other quality parameters of
      the tablets are also monitored simultaneously. It will be demonstrated that,
      besides the API content, the water content of the tablets as well as the
      homogeneity of the other compounds is monitored.

PMID- 16285656
TI  - Label-free detection of proteins in crude cell lysate with antibody arrays by a
      surface plasmon resonance imaging technique.
AB  - We established a label-free method of measuring proteins in crude cell lysate
      using antibody arrays and surface plasmon resonance (SPR) imaging. The
      refractivity of the running buffer was adjusted with that of the lysate to
      overcome the bulk effect. The chemistries of the fabricated arrays were
      investigated to reduce nonspecific adsorption on the array surface. We found that
      the hydrophilicity of the poly(ethylene glycol) moiety and lower electrostatic
      charge on the surface provided a specific measurement of antigen-antibody
      interaction. We validated the system by measuring the expression of eight
      proteins in the mouse brain and comparing the results to those by conventional
      Western blotting. The detection limit of the antibody array was approximately 30
      ng/mL in crude cell lysate, on the same order as that of previous SPR research.
      The system enabled quick, label-free, and high-throughput analysis of abundant
      proteins with minimal sample volume ( approximately 200 muL). It is expected that
      our SPR antibody array will be applicable for direct protein expression profiling
      of cell lysate, as well as for cell phenotyping, food analysis, discovery of new
      biomarkers, and immunological disease diagnostics.

PMID- 16285657
TI  - Thermoplastic microfluidic platform for single-molecule detection, cell culture,
      and actuation.
AB  - We have developed a multipurpose microfluidic platform that allows for sensitive
      fluorescence detection on inexpensive disposable chips. The fabrication scheme
      involves rapid injection molding of thermoplastics, followed by silica deposition
      and covalent attachment of an unstructured flexible lid. This combines the
      virtues of elastomer technology with high-throughput compact disk injection
      molding. Using this technique, the time to produce 100 chips using a single
      master can be lowered from more than 1 week by standard PDMS technologies to only
      a couple hours. The optical properties of the fabricated chips were evaluated by
      studying individual fluorescence-labeled DNA molecules in a microchannel.
      Concatemeric DNA molecules were generated through rolling circle replication of
      circular DNA molecules, which were labeled by hybridization of fluorescence
      tagged oligonucleotides. Rolling circle products (RCPs) were detected after as
      little as 5 min of DNA polymerization, and the RCPs in solution showed no
      tendency for aggregation. To illustrate the versatility of the platform, we
      demonstrate two additional applications: The flexible property of the lid was
      used to create a peristaltic pump generating a flow rate of 9 nL/s.
      Biocompatibility of the platform was illustrated by culturing Chinese hamster
      ovary cells for 7 days in the microfluidic channels.

PMID- 16285658
TI  - Microfluidic electrocapture for separation of peptides.
AB  - A separation method based on electroimmobilization and sequential release of
      captured molecules is reported. A microfluidic electrocapture device is utilized
      to immobilize peptides in a microflow stream. After capture, the electric field
      is decreased in a stepwise manner, causing sequential release of the captured
      peptides according to their electrophoretic mobility. Tryptic peptides were
      separated and analyzed by matrix-assisted laser desorption/ionization mass
      spectrometry. The separation power was high enough to increase the ionization
      yield of several peptides not seen in the unprocessed sample. In addition to
      separation, simultaneous sample cleanup was demonstrated for peptides obtained by
      shotgun tryptic digestion of membrane protein extracts.

PMID- 16285659
TI  - Intrinsic viscosity of polymers and biopolymers measured by microchip.
AB  - Intrinsic viscosity provides insight to molecular structure and interactions in
      solution. A new microchip method is described for fast and accurate measurements
      of viscosity and intrinsic viscosity of polymer and biopolymer solutions. Polymer
      samples are diluted with solvent in the microfluidic chip by imposing pressure
      gradients across the channel network. The concentration and flow dilutions of the
      polymer sample are calculated from the fluorescent signals recorded over a range
      of dilutions. The viscosities at various polymer dilutions are evaluated using
      mass and momentum balances in the pressure-driven microchannel flow. The
      technique is particularly important to many chemical, biological, and medical
      applications where sample is available in very small quantities. The intrinsic
      viscosity experiments were performed for three classes of polymer solutions: (a)
      poly(ethylene glycol), polymers with linear hydrocarbon chains; (b) bovine serum
      albumin, biopolymer chains with hydrophobic and hydrophilic amino acids, and (c)
      DNA fragments, biological macromolecules with double-stranded polymeric chains.
      The measured values of intrinsic viscosity agree remarkably well with the
      available data obtained using different methods. The data exhibit power law
      behavior for molecular weight as described by the Mark-Houwink-Sakurada equation.
      Experiments were performed to understand the effect of solvent quality and salt
      concentration on molecular conformations and the intrinsic viscosity of the
      polymers. This method offers a new way to study the conformational changes in
      proteins and DNA solutions in various buffer conditions such as pH, ionic
      strength, and surfactants. The effects of shear rate in the microchannel and
      mixing time on the accuracy and limitation of the measurement method are
      discussed.

PMID- 16285660
TI  - A strategy for single supersaturated droplet analysis: confocal Raman
      investigations on the complicated hygroscopic properties of individual MgSO4
      droplets on the quartz substrate.
AB  - We report a new strategy for single supersaturated droplet analysis, i.e., the
      complicated hygroscopic properties of MgSO4 aerosols under supersaturated state
      were studied through the micro-Raman observation on an individual MgSO4 droplet
      deposited on a quartz substrate in a relative-humidity-controlled chamber. Upon
      reduction of the ambient relative humidity (RH), MgSO4 droplets with tiny volume
      lost water but did not effloresce. Thus, a detailed spectral evolution of the
      symmetric stretching vibration band (v1-SO4(2-)) from free ions (at approximately
      983 cm(-1)) to monodentate (approximately 995 cm(-1)) and then to bidentate
      contact ion pairs (CIPs) or more complex chain-structural compositions
      (approximately 1021 cm(-1)) was observed with the high signal-to-noise (S/N)
      confocal Raman spectra of the droplet with a diameter of approximately 80
      microns. Such a transition process could be well-described by the changes of
      relative intensity at 983, 995, and 1021 cm(-1). Four steps, i.e., concentrated
      step, monodentate CIPs step, bidentate CIPs step, and gel step, were roughly
      observed in the dehumidifying-humidifying cycle according to the intensity ratios
      of I995/I983 and I1021/I983. Even though the area ratio of the O-H stretching
      band of water molecules to the v1-SO4(2-) band seemed reversible in the
      dehumidifying and humidifying processes, the intensity ratios of I995/I983 and
      I1021/I983 showed a hysteresis in the decomposition of CIPs in the humidifying
      process with the RH < 40%. The O-H stretching envelope of the MgSO4 droplet was
      also observed to be sensitive to the structural changes of the hydrogen bonding
      of water molecules in the four steps. The intensity ratio of Raman scattering for
      the components with strong hydrogen bonds to those with weak ones, i.e.,
      I3224/I3431, was used to understand the effects of CIPs on the water structures
      of the first hydration layer of Mg2+. Good consistency on the hysteresis in the
      humidifying process was also observed from the ratio of I3224/I3431 changing with
      RH.

PMID- 16285661
TI  - Ultrasensitive magnetic particle-based immunosupported liquid membrane assay.
AB  - A magnetic particle-based immuno-supported liquid membrane assay (m-ISLMA) based
      on chemiluminescence detection of a horseradish peroxidase-labeled hapten tracer
      that allows sample cleanup, analyte enrichment, and detection in a single
      analysis unit has been developed. Antibodies were immobilized on magnetic beads,
      and their position in the acceptor was controlled by two alternating opposing
      electromagnetic fields generated by a voltage applied to either of two
      electromagnets placed below and above the acceptor channel of the supported
      liquid membrane unit. The influence of antibody bead dilution in the acceptor was
      investigated and found to follow the ISLM theory, that is improved enrichment and
      sensitivity with increasing antibody concentration. Two different extraction
      procedures were investigated: procedure 1 (m-ISLMA-P1), which keeps the antibody
      beads trapped at the bottom of the acceptor during the entire analysis process;
      and procedure 2 (m-ISLMA-P2), which keeps the antibody beads dispersed and in
      motion in the acceptor phase during the extraction process. m-ISLMA-P2 resulted
      in 2000 times improved enrichment of simazine and a more than 3 orders of
      magnitude better limit of detection (LOD(10%)) (1.29 x 10(-5) microg L(-1)) than
      for m-ISLMA-P1 (2.00 x 10(-2) microg L(-1)) and corresponding microtiter plate
      magnetic particle-based ELISA (m-ELISA, LOD(10%) 1.30 x 10(-1) microg L(-1)). m
      ISLMA-P2 and m-ELISA were further applied for the extraction and analysis of
      simazine-spiked surface water and fruit juice, finding no evidence for matrix
      influence for the former method; however, indications that trace amounts
      (nanograms per liter) of simazine or specific cross-reactants were present in
      both samples.

PMID- 16285662
TI  - Combined top-down and bottom-up mass spectrometric approach to characterization
      of biomarkers for renal disease.
AB  - Here we describe a mass spectrometry (MS) approach for biomarker discovery and
      structural characterization, based on both top-down and bottom-up analyses.
      Capillary electrophoresis (CE) coupled to electrospray ionization (ESI) time-of
      flight (TOF) MS serves to separate and mass-measure the thousands of polypeptides
      contained in human urine. Statistical analysis of the differences between healthy
      control samples and patients with focal-segmental glomerulosclerosis, membranous
      glomerulonephritis, minimal change disease, IgA nephropathy, and diabetic
      nephropathy validates multiple biomarkers for the control and each of the
      diseases. To identify those biomarkers, we employ preparative CE, enabling direct
      infusion ESI MS analysis, followed by sample manipulation and reanalysis where
      necessary. We show how tandem Fourier transform ion cyclotron resonance (FT-ICR)
      MS identifies these sometimes large (>8 kDa) biomarkers. Critically, we maintain
      connectivity between the CE TOF MS data and the ICR data used for biomarker
      identification.

PMID- 16285663
TI  - Using comprehensive two-dimensional gas chromatography retention indices to
      estimate environmental partitioning properties for a complete set of diesel fuel
      hydrocarbons.
AB  - Comprehensive two-dimensional gas chromatography (GCxGC) provides nearly complete
      composition data for some complex mixtures such as petroleum hydrocarbons.
      However, the potential wealth of physical property information contained in the
      corresponding two-dimensional chromatograms is largely untapped. We developed a
      simple but robust method to estimate GCxGC retention indices for diesel-range
      hydrocarbons. By exploiting n-alkanes as reference solutes in both dimensions,
      calculated retention indices were insensitive to uncertainty in the enthalpy of
      gas-stationary-phase transfer for a suite of representative diesel components. We
      used the resulting two-dimensional retention indices to estimate the liquid vapor
      pressures, aqueous solubilities, air-water partition coefficients, octanol-water
      partition coefficients, and vaporization enthalpies of a nearly complete set of
      diesel fuel hydrocarbons. Partitioning properties were typically estimated within
      a factor of 2; this is not as accurate as some previous estimation or measurement
      methods. However, these relationships may allow powerful and incisive analysis of
      phase-transfer processes affecting petroleum hydrocarbon mixtures in the
      environment. For example, GCxGC retention data might be used to quantitatively
      deconvolve the effects of water washing and evaporation on environmentally
      released diesel fuels.

PMID- 16285664
TI  - Automation of a surface sampling probe/electrospray mass spectrometry system.
AB  - An image analysis automation concept and the associated software (HandsFree
      TLC/MS) were developed to control the surface sampling probe-to-surface distance
      during operation of a surface sampling electrospray system. This automation
      system enables both "hands-free" formation of the liquid microjunction used to
      sample material from the surface and hands-free reoptimization of the
      microjunction thickness during a surface scan to achieve a fully automated
      surface sampling system. The image analysis concept and the practical
      implementation of the monitoring and automated adjustment of the sampling probe
      to-surface distance (i.e., liquid microjunction thickness) are presented. The
      added capabilities for the preexisting surface sampling electrospray system
      afforded through this software control are illustrated by an example of automated
      scanning of multiple development lanes on a reversed-phase C8 TLC plate and by
      imaging inked lettering on a paper surface. The post data acquisition processing
      and data display aspects of the software package are also discussed.

PMID- 16285665
TI  - Subcellular analysis of D-aspartate.
AB  - D-Aspartate (D-Asp) is an especially intriguing molecule found within neurons of
      the central nervous system of animals ranging from mollusks to vertebrates. It
      has a large variety of roles ascribed to it, including an involvement in cell-to
      cell signaling. To determine the D-Asp content in cells and in subcellular
      domains, a laboratory-assembled capillary electrophoresis system with laser
      induced fluorescence (LIF) detection has been used. The system allows chiral
      separations with sufficient sensitivity and selectivity to measure the D-Asp
      content in specific subregions of a single neuron, including neuronal processes.
      The method uses microvial sampling, analyte derivatization with naphthalene-2,3
      dicarboxaldehyde, cyclodextrin-mediated micellar electrokinetic capillary
      chromatography, and sheath flow cell-based LIF detection. Manipulating neuronal
      processes is difficult as they often disintegrate during the transfer to the
      sampling vial. We describe a glycerol treatment that stabilizes cell morphology
      during sample preparation, thereby alleviating the deleterious effects of the
      high-salt extracellular matrix on the electrophoretic separation. D-Asp
      percentages in processes from identified neurons from Aplysia californica differ
      significantly depending on the cell studied. Subcellular analysis reveals more
      compounds in the cell body than in the processes.

PMID- 16285666
TI  - Species-specific identification of mycobacterial 16S rRNA PCR amplicons using
      smart probes.
AB  - Due to growing problems with new emerging pathogens, cost-effective and
      manageable methods for their accurate identification in routine diagnostics are
      urgently required. Of particular importance is the genus Mycobacterium with its
      more than 100 species. Identification of these species is hampered by their slow
      growth in the laboratory and by the obligate need for DNA sequence analysis. To
      provide a fast and reliable diagnostic tool, we developed a novel approach using
      fluorescently labeled DNA hairpin structures (smart probes) for selective and
      sensitive detection of mycobacterial 16S rDNA PCR amplicons in homogeneous and
      heterogeneous assays. Smart probes are singly labeled hairpin-shaped
      oligonucleotides bearing a fluorescent dye at the 5'-end, which is quenched by
      guanosine residues in the complementary stem. Upon hybridization to target
      sequences, a conformational change occurs reflected in an increase in
      fluorescence intensity. Using optimized parameters for hybridization experiments
      we established a reliable method for the specific detection of Mycobacterium
      tuberculosis (M. tuberculosis complex) and Mycobacterium xenopi (member of the
      atypical mycobacteria) with a detection sensitivity of approximately 2 x 10(-8) M
      in homogeneous solution. The specificity of the smart probes designed is
      demonstrated by discrimination of M. tuberculosis and M. xenopi against 15 of the
      most frequently isolated mycobacterial species in a single assay. In combination
      with a microsphere-based heterogeneous assay format, the technique opens new
      avenues for the detection of pathogen-specific DNA sequences with hitherto
      unsurpassed sensitivity.

PMID- 16285667
TI  - Dextran-gold nanoparticle hybrid material for biomolecule immobilization and
      detection.
AB  - The formation of a hybrid metal-biopolymer material is described. The synthesis
      of this material consists of functionalizing the surface of gold nanoparticles
      through a series of steps that lead to epoxy-functionalized nanoparticles. These
      are subsequently reacted with hydroxyl moieties of the alpha-D-glucopyranosyl
      groups of dextran. Subsequently, the dextran chains are carboxylated through
      treatment with bromoacetic acid. The resultant material combines the unique
      optical properties of gold nanoparticles with the versatility that carboxylated
      dextran offers for further functionalization with biomolecules. The interaction
      of this material with three proteins was then investigated through changes in the
      plasmon resonance properties of the gold nanoparticles. Concanavalin A, a lectin
      that binds glucose and mannose by means of specific molecular recognition,
      interacts readily with this material and such interaction is easily detected
      using optical absorption spectroscopy. Through reaction of the carboxyl groups
      with (+)-biotinyl-3,6,9,-trioxaundecanediamine, a material bearing biotin groups
      was obtained. This could interact with streptavidin or antibiotin by means of
      specific molecular recognition. Further confirmation of biospecific interactions
      was obtained with control experiments in which the binding sites were blocked
      through preincubation of the proteins with the corresponding ligand in solution.
      Binding of these proteins was concentration-dependent over a wide concentration
      range. This material provides a simple and convenient colorimetric method for
      biospecific interaction analysis.

PMID- 16285668
TI  - Comparative analysis of cellulose preparation techniques for use with 13C, 14C,
      AND 18O isotopic measurements.
AB  - A number of operationally defined methods exist for pretreating plant tissues in
      order to measure C, N, and O isotopes. Because these isotope measurements are
      used to infer information about environmental conditions that existed at the time
      of tissue growth, it is important that these pretreatments remove compounds that
      may have exchanged isotopes or have been synthesized after the original formation
      of these tissues. In stable isotope studies, many pretreatment methods focus on
      isolating "cellulose" from the bulk tissue sample because cellulose does not
      exchange C and O isotopes after original synthesis. We investigated the efficacy
      of three commonly applied pretreatment methods, the Brendel method and two
      variants of the Brendel method, the Jayme-Wise method and successive
      acid/base/acid washes, for use on three tissue types (wood, leaves, roots). We
      then compared the effect of each method on C and O isotope composition (13C, 14C,
      18O), C and N content, and chemical composition of the residue produced (using
      13C nuclear magnetic resonance (NMR)). Our results raised concerns over use of
      the Brendel method as published, as it both added C and N to the sample and left
      a residue that contains remnant lipids and waxes. Furthermore, this method
      resulted in 18O values that are enriched relative to the other methods. Modifying
      the Brendel method by adding a NaOH step (wash) solved many of these problems. We
      also found that processed residues vary by tissue type. For wood and root
      tissues, the 13C NMR spectra and the 18O and 13C data showed only small
      differences between residues for the Jayme-Wise and modified Brendel methods.
      However, for leaf tissue, 13C NMR data showed that Jayme-Wise pretreatments
      produced residues that are more chemically similar to cellulose than the other
      methods. The acid/base/acid washing method generated 13C NMR spectra with
      incomplete removal of lignin for all tissues tested and both isotopic, and 13C
      NMR results confirmed that this method should not be used if purified cellulose
      is desired.

PMID- 16285669
TI  - Comparative glycoproteomics of N-linked complex-type glycoforms containing sialic
      acid in human serum.
AB  - This study describes a simple and efficient approach for comparative analysis of
      sialylated glycoforms of proteins containing differentially branched complex-type
      glycans. The analytical protocol is based on glycopeptide selection from tryptic
      digests with serial lectin affinity chromatography (SLAC), quantification with
      global internal standard technology, fractionation of deglycosylated peptides
      with reversed-phase chromatography, and peptide sequencing with tandem mass
      spectrometry. Fractionation of complex tri- and tetraantennary N-linked
      glycoforms from biantennary N-linked glycoforms bearing terminal sialic acid
      residues was achieved using a set of serial lectin columns with immobilized
      Sambucus nigra agglutinin and concanavalin A. These two fractions from the
      affinity selection were differentially labeled, mixed, and then deglycosylated
      with the enzyme PNGase F. The deglycosylated sample was further fractionated by
      reversed-phase chromatography and analyzed by electrospray ionization mass
      spectrometry. The SLAC strategy was applied to tryptic digests of human serum,
      and it was found that most sialylated glycopeptides identified carry more
      biantennary glycans than tri- and tetraantennary glycans, and the relative amount
      of biantennary glycan versus tri- and tetraantennary glycans was different at
      separate glycosylation sites within the same glycoprotein.

PMID- 16285670
TI  - Reliability of human serum protein profiles generated with C8 magnetic beads
      assisted MALDI-TOF mass spectrometry.
AB  - Protein profiling with mass spectrometry is a promising approach for
      classification and identification of biomarkers; however, there is debate about
      measurement quality and reliability. Here, we present a pipeline for
      preprocessing, statistical data analysis and presentation. Serum samples of 16
      healthy individuals are used to generate protein profiles with high-resolution
      MALDI-TOF after isolation of peptides with C8 magnetic beads. Analysis of
      variance was performed after binning, baseline correction and normalization of
      the mean spectra. Relative variations in the spectra are expressed as coefficient
      of variation, which depending on the respective preanalytical variation parameter
      investigated, was found to range between 0.15 and 0.67 in this study. With this
      novel method, the reproducibility of our protein profiling procedure could be
      quantified. We showed that circadian rhythm and the number of freeze-thaw cycles
      had relatively limited influence on serum protein profiles, whereas the period
      between collection and serum centrifugation had a more pronounced effect.

PMID- 16285671
TI  - Improvement of immunodetection of bacterial spore antigen by ultrasonic
      cavitation.
AB  - Ultrasonic cavitation was employed to enhance sensitivity of bacterial spore
      immunoassay detection, specifically, enzyme-linked immunosorbent assay (ELISA)
      and resonant mirror (RM) sensing. Bacillus spore suspensions were exposed to high
      power ultrasound in a tubular sonicator operated at 267 kHz in both batch and
      flow modes. The sonicator was designed to deliver high output power and is in a
      form that can be cooled efficiently to avoid thermal denaturation of antigen. The
      30-s batch and cooled flow (0.3 mL/min) sonication achieved an approximately 20
      fold increase in ELISA sensitivity compared to unsonicated spores by ELISA. RM
      sensing of sonicated spores achieved detection sensitivity of approximately 10(6)
      spores/mL, whereas unsonicated spores were undetectable at the highest
      concentration tested. Improvements in detection were associated with antigen
      released from the spores. Equilibrium temperature increase in the tubular
      sonicator was limited to 14 K after 30 min and was maintained for 6 h with
      cooling and flow (0.3 mL/min). The work described here demonstrates the utility
      of the tubular sonicator for the improvement in the sensitivity of the detection
      of spores and its suitability as an in-line component of a rapid detection
      system.

PMID- 16285672
TI  - Multicomponent internal recalibration of an LC-FTICR-MS analysis employing a
      partially characterized complex peptide mixture: systematic and random errors.
AB  - In high-throughput proteomics, a promising current approach is the use of liquid
      chromatography coupled to Fourier transform ion cyclotron resonance mass
      spectrometry (LC-FTICR-MS) of tryptic peptides from complex mixtures of proteins.
      To apply this method, it is necessary to account for any systematic measurement
      error, and it is useful to have an estimate of the random error expected in the
      measured masses. Here, we analyze by LC-FTICR-MS a complex mixture of peptides
      derived from a sample previously characterized by LC-QTOF-MS. Application of a
      Bayesian probability model of the data and partial knowledge of the composition
      of the sample suffice to estimate both the systematic and random errors in
      measured masses.

PMID- 16285673
TI  - Controlled protein precipitation in combination with chip-based nanospray
      infusion mass spectrometry. An approach for metabolomics profiling of plasma.
AB  - Liquid chromatography-mass spectrometry (LC-MS) is a common method for profiling
      biological samples in metabolomics. However, LC-MS data of metabolomic studies
      are often affected by high noise levels, retention time shifts, and high
      variability in signal intensities. With a new chip-based nanoelectrospray source
      it becomes possible to directly infuse complex biological samples such as plasma
      without any chromatographic separation beforehand. In combination with highly
      diluted samples and long data acquisition times, the parallel analysis of
      hundreds of compounds is now possible. In a proof-of-concept study, 10 human
      plasma samples from females and males were analyzed with the intention to
      separate the two groups by their different metabolomes. The reproducibility was
      so high that statistical analysis of the data could be performed without prior
      normalization. Two groups of female and male samples were separated by a
      supervised machine learning algorithm, principal component analysis, and
      hierarchical clustering. Peaks contributing to the group separation were
      characterized by accurate mass measurement and MS-MS fragmentation and by spiking
      experiments. The feasibility of direct sample infusion using the new chip-based
      nanoelectrospray device opens a new dimension for the rapid parallel analysis of
      complex biological mixtures.

PMID- 16285674
TI  - NovoHMM: a hidden Markov model for de novo peptide sequencing.
AB  - De novo sequencing of peptides poses one of the most challenging tasks in data
      analysis for proteome research. In this paper, a generative hidden Markov model
      (HMM) of mass spectra for de novo peptide sequencing which constitutes a novel
      view on how to solve this problem in a Bayesian framework is proposed. Further
      extensions of the model structure to a graphical model and a factorial HMM to
      substantially improve the peptide identification results are demonstrated.
      Inference with the graphical model for de novo peptide sequencing estimates
      posterior probabilities for amino acids rather than scores for single symbols in
      the sequence. Our model outperforms state-of-the-art methods for de novo peptide
      sequencing on a large test set of spectra.

PMID- 16285675
TI  - Probing protein tertiary structure with amidination.
AB  - A chemical derivatization method, amidination, that has recently been effectively
      employed in peptide mass spectrometry experiments is used to covalently modify
      lysines in several standard proteins. Protein and peptide mass spectra identify
      sites at which the reaction does or does not occur. This is therefore a rapid
      approach to elucidate solvent-accessible regions of folded proteins.

PMID- 16285676
TI  - Analysis of lipoproteins by microchip electrophoresis with high speed and high
      reproducibility.
AB  - A method for the fast analysis of lipoproteins by microchip electrophoresis with
      light-emitting diode confocal fluorescence detection has been developed.
      Lipoproteins labeled with BODIPY FL C(5)-ceramide are found to strongly adsorb on
      the bare surface of a poly(methyl methacrylate) (PMMA) microchip. Sodium dodecyl
      sulfate and cetyltrimethylammonium bromide were therefore utilized to alter
      lipoproteins and channel surface to make them bear the same type of charge. After
      modification, the peak shape of lipoproteins was greatly improved, demonstrating
      lipoprotein adsorption on a PMMA chip dramatically reduced due to electrostatic
      repulsion. In addition, polymers were added into the running buffer to suppress
      electroosmotic flow and to serve as a sieving matrix. As a result, lipoprotein
      separation was manipulated by both electrophoretic mobilities and particle sizes.
      Various separation parameters including surfactant concentration, buffer pH, and
      polymer concentration as well as on-line concentration were investigated
      systematically. Under optimal conditions, two baseline separations of standard
      lipoproteins including high-density lipoprotein, low-density lipoprotein, and
      very low-density lipoprotein were achieved with different selectivity. This
      method affords high separation speed (within 100 s) and high reproducibility. The
      intraassay and interassay RSDs of lipoprotein migration times were in the range
      of 0.90-1.9%, indicating this method is highly reliable.

PMID- 16285677
TI  - Carbon-specific analysis of humic-like substances in atmospheric aerosol and
      precipitation samples.
AB  - A new approach for the carbon-specific determination of humic-like substances
      (HULIS) in atmospheric aerosols is presented. The method is based on a two-step
      isolation procedure of HULIS and the determination of HULIS carbon with a
      dissolved organic carbon analyzer. In the first step, a C18 solid-phase
      extraction is performed to separate HULIS from inorganic and hydrophilic organic
      sample constituents in aqueous sample solutions. The second isolation step is
      conducted on a strong anion exchanger to separate HULIS from remaining
      carbonaceous compounds. This ion chromatographic separation step including the
      subsequent on-line detection of HULIS carbon was performed fully automated to
      avoid the risk of sample contamination and to enhance the reproducibility of the
      method. With a 5-mL sample volume, a limit of detection of 1.0 mg C/L was
      obtained; this corresponds to an absolute amount of 5 microg of HULIS carbon. The
      reproducibility of the method given as the relative standard deviation was 4.3%
      (n = 10). The method was applied for the determination of water-soluble HULIS in
      airborne particulate matter. PM10 concentrations at an urban site in Vienna,
      Austria, ranged from around 0.1 to 1.8 microg of C/m(3) (n = 49); the fraction of
      water-soluble HULIS in OC was 12.1 +/- 7.2% (n = 49).

PMID- 16285679
TI  - Electrochemical telomerase assay with ferrocenylnaphthalene diimide as a
      tetraplex DNA-specific binder.
AB  - Spectroscopic studies revealed that ferrocenylnaphthalene diimide (1) can bind to
      tetraplex DNA at high potassium ion concentration. The tetraplex DNA was
      stabilized by the binding of 1, and this effect was larger than that of any other
      tetraplex stabilizers, which are known as a telomerase inhibitor. Quantitative
      analysis with circular dichroism and a quartz crystal microbalance strongly
      suggested a 3:1 binding stoichiometry of 1 to the tetraplex DNA. The telomere
      sequence could be extended by telomerase with the telomerase substrate primer on
      the surface of an electrode as proven by an increased current signal of 1 bound
      to the tetraplex DNA formed on the electrode. This is the first example of
      electrochemical detection of telomerase activity without relying on PCR.

PMID- 16285680
TI  - Electrochemically modulated liquid-liquid extraction of ions.
AB  - The development of ion extraction methods under electrochemical control via
      electrochemistry at the interface between two immiscible electrolyte solutions is
      discussed. A hydrodynamic flow injection system was used for the potentiostatic
      extraction of non-redox-active species from a flowing aqueous phase into a
      stationary organogel phase. The ions tetraethylammonium, 4-octylbenzenesulfonate
      (4-OBSA-), and p-toluenesulfonate (p-TSA-) were studied as model analytes. The
      extraction study comprised examination of the influence of extraction potentials,
      aqueous-phase flow rate, and target species concentration. The extraction process
      can be monitored in situ by means of the ion-transfer current, which has opposing
      signs for anions and cations. Hydrodynamic voltammograms were obtained from these
      experiments. The selective extraction of 4-OBSA-, from its mixture with p-TSA-,
      as well as coextraction of both anions is shown. The results demonstrate the
      utility of electrochemical modulation for the controlled extraction of ions from
      an aqueous phase into an organogel electrolyte phase. This offers potential
      benefits for various analytical processes including sample preparation and
      cleanup.

PMID- 16285678
TI  - Copper ion-selective fluorescent sensor based on the inner filter effect using a
      spiropyran derivative.
AB  - A highly selective copper(II) ion fluorescent sensor has been designed based on
      the UV-visible absorption of a spiropyran derivative coupled with the use of a
      metal porphyrin operative on the fluorescence inner filter effect. Spiropyrans,
      which combine the characteristics of metal binding and signal transduction, have
      been widely utilized in cationic ion recognition by UV-visible spectroscopy. In
      the present work, the viability of converting the absorption signal of the
      spiropyran molecule into a fluorescence signal was explored. On account of
      overlap of the absorption band of the spiropyran (lambda(abs) = 547 nm) in the
      presence of copper ion with the Q-band of an added fluorophore, zinc meso
      tetraphenylporphyrin (lambda(abs) = 556 nm), the effective light absorbed by the
      porphyrin and concomitantly the emitted light intensity vary as a result of
      varying absorption of the spiropyran via fluorescence inner filter effect. The
      metal binding characteristic of the spiropyran presents an excellent selectivity
      for copper ion in comparison with several other heavy or transition metal ions.
      Since the changes in the absorbance of the absorber translate into exponential
      changes in fluorescence of the fluorophore, the novelty of the present device is
      that the analytical signal is more sensitive over that of the absorptiometry or
      that of the fluorometry using one single dye. To realize a practical fluorescent
      sensor, both the absorber and fluorophore were immobilized in a plasticized
      poly(vinyl chloride) membrane, and the sensing characteristics of the membrane
      for copper ion were investigated. The sensor is useful for measuring Cu2+ at
      concentrations ranging from 7.5 x 10(-7) to 3.6 x 10(-5) M with a detection limit
      of 1.5 x 10(-7) M. The sensor is chemically reversible, the fluorescence was
      switched off by immersing the membrane in copper ion solution and switched on by
      washing it with EDTA solution.

PMID- 16285681
TI  - Time-weighted average water sampling with a solid-phase microextraction device.
AB  - A fiber-in-needle SPME device was developed and investigated for time-weighted
      average water sampling. The device was designed so that the overall mass-transfer
      resistance is contained within the static water inside the needle, which ensures
      that mass uptake could be predicted with Fick's first law of diffusion and the
      sampling rate is less affected by water turbulence. The device possesses all of
      the advantages of commercialized devices, in addition to needle filling and
      replacement ease. Laboratory calibration with deployment of the device to a flow
      through system demonstrated that there was a linear mass uptake for up to 12
      days, and the linear range could be longer. PDMS coating is assumed to be a
      perfect zero sink for most polycyclic aromatic hydrocarbons, except naphthalene.
      The effect of water temperature was also investigated. Under normal field
      conditions, the change of mass uptake rate with temperature was negligible. To
      facilitate the convenience for long-term water sampling, a new standard aqueous
      generator was introduced. This study extended the application of SPME technology
      for long-term water sampling.

PMID- 16285682
TI  - Kinetic and equilibrium binding analysis of protein-ligand interactions at
      poly(amidoamine) dendrimer monolayers.
AB  - The interaction of streptavidin (SA) with a biotinylated surface has been of
      great interest in the development of an interfacial layer for protein
      immobilization based on self-assembled monolayers (SAMs) and polymeric layers.
      Here, we demonstrate the unique characteristics of protein-ligand interactions on
      dendrimer monolayers based on kinetic and equilibrium binding analyses. With
      amine-ended poly(amidoamine) dendrimers from the first (G1) to fourth (G4)
      generation, the formation of even, compact dendrimer monolayers on gold was
      confirmed using FT-IR spectroscopy and ellipsometry. For the SA-biotin
      interaction, quantitative analysis of bound SA using surface plasmon resonance
      showed that the saturation binding level of SA was fairly higher in all dendrimer
      layers when compared to other tested systems of 11-mercaptoundecylamine SAMs and
      a poly(L-lysine) layer. Kinetic studies revealed that the initial binding rate of
      SA up to the saturation level was 2-fold higher in all dendrimer layers than in
      the SAMs regardless of the surface density of functionalized biotin.
      Concurrently, the dendrimer layers led to much higher values of sticking
      probability, which is defined as the probability that the SA molecule adsorbs
      upon collision with a biotinylated surface, at a fixed SA coverage, and prolonged
      the significant levels around the maximum probability with increasing SA
      coverage. Plots of the saturation coverage of SA versus the SA concentration in
      solution showed that SA binding onto the biotinylated G1 and G3 layers fit to a
      Langmuir isotherm model. Taken together, faster binding of SA and highly ordered
      packing of the molecules seems to be achieved through typical properties of the
      dendrimer monolayers such as surface distribution of functionalized biotin,
      surface corrugation, and flexibility of highly branched larger dendrimers, which
      provides a guideline for the construction and analysis of an interfacial layer in
      biosensing applications.

PMID- 16285683
TI  - Thorium complexation by hydroxamate siderophores in perturbed multicomponent
      systems using flow injection electrospray ionization mass spectrometry.
AB  - Flow injection electrospray ionization mass spectrometry has been shown to
      produce simple, characteristic m/z signals for Th-hydroxamate siderophore
      (desferrioxamine and ferrichrome) complexes, with Th complexed as a simple 4+ ion
      in the environmentally relevant pH range investigated (pH 5-9). All species of
      interest for this study were identified optimally in the positive mode; thus,
      multiple species were analyzed concurrently in a single spectrum. Complexation of
      Th by the two siderophores was rapid in 1:1 molar aqueous solution, reaching
      equilibrium before the first measurement was possible at 2 min. However, a
      significant proportion of the equimolar siderophore remained uncomplexed. Both
      siderophores rapidly exchanged Th for Fe when equimolar Fe(III) was added to the
      Th complexes, and only a small proportion of each siderophore remained complexed
      with Th at equilibrium (7-30 min). The results show a difference in the
      affinities of the two siderophores for the metals; ferrichrome has a 5-fold
      higher affinity than desferrioxamine for Th and a 5-fold lower affinity than
      desferrioxamine for Fe. Also, siderophore-complexed Th interacted strongly with a
      cation-exchange resin suggesting that, even when complexed by trianionic
      siderophores, Th mobility will be impeded by interactions with negatively charged
      binding sites in subsurface environmental matrixes. These results have important
      implications regarding siderophore-enhanced actinide(IV) mobility in the
      terrestrial environment.

PMID- 16285684
TI  - Tailoring the morphology of methacrylate ester-based monoliths for optimum
      efficiency in liquid chromatography.
AB  - Methacrylate ester-based monolithic stationary phases were prepared in situ in
      fused-silica capillaries and simultaneously in vials. The influence of the
      composition of the polymerization mixture on the morphology was studied with
      mercury intrusion porosimetry, scanning electron microscopy, and nitrogen
      adsorption measurements. A high-density porous polymeric material with a unimodal
      pore-size distribution was prepared with 40 wt % monomers and 60 wt % solvent in
      the mixture. A low-density material, prepared with a 20:80 ratio of monomers
      versus pore-forming solvent, showed a bimodal pore-size distribution and a much
      finer structure than the high-density monolith. The characteristic pore size
      could be controlled by changing the ratio of pore-forming solvents. With
      increasing solvent polarity, both the pore size and the dimension of the globules
      increased. The best efficiency in the CEC mode was obtained with an average pore
      size of 600 nm. Low-density monoliths exhibited lower A- and C-terms than high
      density monoliths. With the optimal monolithic material, a minimum plate height
      of 5 mum could be obtained. The low-density monolith also performed better in the
      HPLC mode, giving a minimum plate height of 15 mum and a much higher flow
      permeability than that of the high-density material.

PMID- 16285685
TI  - Homogeneous assay technology based on upconverting phosphors.
AB  - Upconversion photoluminescence can eliminate problems associated with
      autofluorescence and scattered excitation light in homogeneous luminescence-based
      assays without need for temporal resolution. We have demonstrated a luminescence
      resonance energy-transfer-based assay utilizing inorganic upconverting (UPC)
      lanthanide phosphor as a donor and fluorescent protein as an acceptor. UPC
      phosphors are excited at near-infrared and they have narrow-banded anti-Stokes
      emission at visible wavelengths enabling measurement of the proximity-dependent
      sensitized emission with minimal background. The acceptor alone does not generate
      any direct emission at shorter wavelengths under near-infrared excitation. A
      competitive model assay for biotin was constructed using streptavidin-conjugated
      Er3+,Yb3+-doped UPC phosphor as a donor and biotinylated phycobiliprotein as an
      acceptor. UPC phosphor was excited at near-infrared (980 nm) and sensitized
      acceptor emission was measured at red wavelength (600 nm) by using a
      microtitration plate fluorometer equipped with an infrared laser diode and
      suitable excitation and emission filters. Lower limit of detection was in the
      subnanomolar concentration range. Compared to time-resolved fluorometry, the
      developed assay technology enabled simplified instrumentation. Excitation at near
      infrared and emission at red wavelengths render the technology also suitable to
      analysis of strongly colored and fluorescent samples, which are often of concern
      in clinical immunoassays and in high-throughput screening.

PMID- 16285686
TI  - Development of an aerosol chemiluminescent detector coupled to capillary
      electrophoresis for saccharide analysis.
AB  - A novel aerosol chemiluminescent (CL) detector coupling to capillary
      electrophoresis (CE) for the detection of saccharides is reported. This CL
      detector is composed of a postcapillary nebulizer and porous alumina as catalyzer
      in quartz tube. The CL emission could be generated due to the catalyzing
      oxidization of saccharides on the surface of porous alumina. The saccharides such
      as sucrose, alpha-lactose, maltose, raffinose, galactose, xylose, and glucose
      with only weak UV absorbance can be successfully detected. The linear ranges of
      those saccharides are from 30-2000 to 50-2000 mg/L; relative standard deviations
      range from 2.1 to 3.7% (200 mg/L, n = 11). Compared with the traditional UV
      detector currently used in CE, this novel detector shows the advantage of high
      sensitivity to the compounds with only weak UV absorption. Thus, it could be an
      important supplement of CE detectors for UV-lacking compounds.

PMID- 16285687
TI  - Conjugation of keto fatty acids to glutathione in plant tissues. Characterization
      and quantification by HPLC-tandem mass spectrometry.
AB  - Both biotic and abiotic stress activate the oxylipin pathway in plants. As
      reactive electrophile species (RES), some oxylipins are expected to bind cellular
      nucleophiles in a Michael-type addition reaction. Using the HPLC-tandem mass
      spectrometry techniques, we have established the analytical basis for the
      investigation of oxylipin conjugation to glutathione (GSH) in plant extracts. The
      GSH adducts to the four keto fatty acid isomers issued from both linoleic and
      linolenic acids were first produced and their mass spectrometric features
      analyzed in the positive electrospray ionization mode. In all cases, the main
      fragmentation (MS2 mode) of the pseudomolecular ion leads to the neutral loss of
      a glutamyl moiety (-129 Da), affording an ion that gives structural information
      upon an additional fragmentation (MS3 mode). The glutamyl loss was confirmed by
      the analysis of other GSH adducts to oxylipin RES and appeared as being
      characteristic of GSH adducts. It is thus proposed to search GSH adducts in plant
      extracts by HPLC-MS/MS, using initially the neutral loss mode and then the MS2
      mode to further characterize the identified compounds. This methodology was
      successfully applied to the analysis of GSH adducts upon infiltration into leaves
      of the four previous keto fatty acids at 5 mM, a concentration inducing cell
      death. The production of GSH adducts to oxylipin RES was observed for the first
      time in plant tissues. Furthermore, the levels of adduct production explain in
      part the observed GSH depletion. These results support the role of RES in
      altering protein activities and cellular redox balance of plant cells, via
      addition reactions to cellular nucleophiles.

PMID- 16285688
TI  - Potential-dependent adsorption and orientation of a small zwitterion: p
      aminobenzoic acid on Ag(111).
AB  - We report on the potential-dependent behavior of the zwitterionic molecule p
      aminobenzoic acid (PABA) at a Ag(111) electrode surface. Infrared-visible sum
      frequency generation spectroscopy (SFG) in tandem with electrochemical
      capacitance and CV measurements are used to study the effects of applied
      potential on the adsorption and orientation of PABA. Changes in the SFG signal
      indicate that PABA changes orientation in response to the charge on the electrode
      surface, orienting one way positive of the potential of zero charge (pzc) and
      oppositely negative of the pzc. At positive potentials, a phase change is
      observed associated with the formation of a condensed layer. PABA is observed to
      remain on the surface at all potentials examined. These results show that the
      orientation of small molecules with large dipoles, like zwitterions, can be
      controlled by applied potential.

PMID- 16285690
TI  - Surface-enhanced Raman scattering based approach for quantitative determination
      of creatinine in human serum.
AB  - A novel surface-enhanced Raman scattering (SERS) based approach for the
      quantitative determination of creatinine in human serum is described. Using
      isotopically labeled (2-13C, 2,3-15N2) creatinine as internal standard, SERS
      acquires the character of a ratio method that works similar to the well
      established isotope dilution techniques. In conjunction with multivariate data
      analysis, the method was successfully applied for quantifying creatinine at
      clinically relevant levels and below. A partial least-squares regression model
      was generated from a set of 87 calibration spectra covering the full range of
      mole fractions of neat creatinine. The prediction performance of the model was
      thereafter validated with independent reference samples giving a standard
      deviation of less than 2%. Finally, a conditioning procedure to prepare real
      serum samples for SERS-based creatinine analysis was worked out and validated.
      Measured serum creatinine concentrations are within 3% of the values obtained
      from gas chromatography/isotope dilution mass spectrometry on the same serum
      starting material.

PMID- 16285689
TI  - Identification of peptides using gold nanoparticle-assisted single-drop
      microextraction coupled with AP-MALDI mass spectrometry.
AB  - A novel technique, gold nanoparticle-assisted single-drop microextraction (SDME)
      combined with atmospheric pressure matrix-assisted laser desorption/ionization
      mass spectrometry (AP-MALDI-MS) for the identification of peptides has been
      described. The SDME of peptides from aqueous solution was achieved using gold
      nanoparticles prepared in toluene as the acceptor phase. A simple phenomenon of
      isoelectric point (pI) of the peptides has been utilized successfully to extract
      the peptides into a single drop of nanogold in toluene. After extraction, a
      single-drop nano gold solution was directly spotted onto the target plate with an
      equal volume of matrix, proportional, variant-cyanohydroxy cinnamic acid (
      proportional, variant-CHCA) and analyzed in AP-MALDI-MS. The parameters, such as
      solvent selection, extraction time, agitation rate, and pH effect, were optimized
      for the SDME technique. Using this technique, in aqueous solution, the lowest
      concentration detected for Met- and Leu-enkephalin peptides was 0.2 and 0.17
      microM, respectively. In addition, the application of this technique to obtain
      the signal for the selected peptides in a mass spectrum in the presence of matrix
      interferences such as 1% Triton X-100 and 6.5 M urea has been showed. The
      application was extended to identify the peptides spiked into urine.

PMID- 16285691
TI  - Enzyme modification of platinum microelectrodes for detection of cholesterol in
      vesicle lipid bilayer membranes.
AB  - Platinum microelectrodes are modified with a lipid bilayer membrane incorporating
      cholesterol oxidase. Details for electrode surface modification are presented
      along with characterization studies of electrode response to cholesterol solution
      and to cholesterol contained in the lipid bilayer membrane of vesicles.
      Ferrocyanide voltammetric experiments are used to track deposition of a
      submonolayer of a thiol-functionalized lipid on the platinum electrode surface,
      vesicle fusion for bilayer formation on the thiolipid-modified surface, and
      incorporation of cholesterol oxidase in the electrode-supported thiolipid/lipid
      bilayer membrane. The data are consistent with formation of a lipid bilayer
      structure on the electrode surface that contains defects. Experiments for
      detection of cholesterol solubilized in cyclodextrin solution show steady-state
      current responses that correlate with cholesterol concentration. Direct contact
      between the electrode and a vesicle lipid bilayer membrane shows a response that
      correlates with vesicle membrane cholesterol content.

PMID- 16285692
TI  - Electrochemically modulated liquid chromatography and the Gibbs adsorption
      equation.
AB  - Electrochemically modulated liquid chromatography uses a conductive material like
      porous graphitic carbon (PGC) as a chromatographic stationary phase and a working
      electrode. This dual functionality enables manipulation of separations by changes
      in the potential applied (E(app)) to the packing. Thus, by monitoring the
      retention factor (k') with respect to E(app), a chromatographic tool for
      examination of electrosorption processes can be devised. This novel capability is
      developed herein by examining the retention of charged aromatic compounds at PGC.
      The Gibbs adsorption equation and related formulations (e.g., the Lippmann
      equation) are used to determine interfacial excesses (Gamma) of these solutes in
      different supporting electrolytes, changes in interfacial tension (dgamma), the
      charge on the electrode (q(M)), and the potential of zero charge (PZC). Values of
      the PZC were also determined from plots of ln k' versus E(app). In this case, the
      dependence of ln k' reveals a shift in the PZC to more cathodic values as the
      strength of specific adsorption by anions as the electrolyte concentration
      increases. Together, these results provide insights into the retention mechanism
      and, more generally, to adsorption at electrified carbon electrodes. Extensions
      of this strategy as a probe of electrified interfaces with respect to mobile
      phase composition, temperature, and pressure are briefly described.

PMID- 16285694
TI  - Determination of benzotriazole corrosion inhibitors from aqueous environmental
      samples by liquid chromatography-electrospray ionization-tandem mass
      spectrometry.
AB  - The first method for the determination of commonly used corrosion inhibitors in
      environmental water samples by liquid chromatography-electrospray ionization
      tandem mass spectrometry is presented. Benzotriazole (BTri) and the two isomers
      of tolyltriazole (5- and 4-TTri) are separated in an isocratic run. By gradient
      elution, BTri, 4-TTri, 5-TTri, and xylyltriazole can be determined simultaneously
      with three benzothiazoles, but here TTri isomers coelute. The instrumental
      detection limit of 2 pg allows the determination of the three most important
      benzotriazoles from municipal wastewater and most surface waters by direct
      injection into the HPLC system without previous enrichment. When solid-phase
      extraction is employed with mean recovery rates of 95-113%, the limit of
      quantification for benzotriazoles range from 10 ng/L in groundwater to 25 ng/L in
      untreated wastewater. BTri and TTri were determined in municipal wastewater in
      microgram per liter concentrations. Elimination in wastewater treatment appears
      to be poor, and BTri and TTri can be followed through a water cycle from treated
      municipal wastewater through surface water to bank filtrate used for drinking
      water production. The TTri isomers show markedly different biodegradation
      behavior with 4-TTri being more stable.

PMID- 16285693
TI  - Single photon ionization time-of-flight mass spectrometry with a pulsed electron
      beam pumped excimer VUV lamp for on-line gas analysis: setup and first results on
      cigarette smoke and human breath.
AB  - Single-photon ionization (SPI) using vacuum ultraviolet (VUV) light produced by
      an electron beam pumped rare gas excimer source has been coupled to a compact and
      mobile time-of-flight mass spectrometer (TOFMS). The novel device enables real
      time on-line monitoring of organic trace substances in complex gaseous matrixes
      down to the ppb range. The pulsed VUV radiation of the light source is employed
      for SPI in the ion source of the TOFMS. Ion extraction is also carried out in a
      pulsed mode with a short time delay with respect to ionization. The experimental
      setup of the interface VUV light source/time-of-flight mass spectrometer is
      described, and the novel SPI-TOFMS system is characterized by means of standard
      calibration gases. Limits of detection down to 50 ppb for aliphatic and aromatic
      hydrocarbons were achieved. First on-line applications comprised real-time
      measurements of aromatic and aliphatic trace compounds in mainstream cigarette
      smoke, which represents a highly dynamic fluctuating gaseous matrix. Time
      resolution was sufficient to monitor the smoking process on a puff-by-puff
      resolved basis. Furthermore, human breath analysis has been carried out to detect
      differences in the breath of a smoker and a nonsmoker, respectively. Several well
      known biomarkers for smoke could be identified in the smoker's breath. The
      possibility for even shorter measurement times while maintaining the achieved
      sensitivity makes this new device a promising tool for on-line analysis of
      organic trace compounds in process gases or biological systems.

PMID- 16285695
TI  - Quantitative detection system for maize sample containing combined-trait
      genetically modified maize.
AB  - Various countries have established regulations that stipulate the labeling of
      agricultural commodities, feed, and food products that contain or are made from
      genetically modified (GM) material or that contain adventitious GM material in
      amounts that exceed certain threshold levels. While regulations in some countries
      refer to GM material on a weight per weight (w/w) percentage, the currently
      applied detection methods do not directly measure the w/w percentage of the GM
      material. Depending on the particular method and the sample matrix it is applied
      to, the conversion of analytical results to a w/w percentage is challenging or
      not possible. The first rapid PCR system for GM maize detection on a single
      kernel basis has been developed. The equipment for the grinding of individual
      kernels and a silica membrane-based 96-well DNA extraction kit were both
      significantly revised and optimized for this particular purpose, respectively. We
      developed a multiplex real-time PCR method for the rapid quantification of GM DNA
      sequences in the obtained DNA solutions. In addition, a multiplex qualitative PCR
      detection method allows for the simultaneous detection of different GM maize
      traits in each kernel and thereby for identification of individual kernels that
      contain a combination of two or more GM traits. Especially for grain samples that
      potentially contain combined-trait GM maize kernels, the proposed methods can
      deliver informative results in a rapid, precise, and reliable manner.

PMID- 16285697
TI  - Equilibrium partitioning model applied to RDX-halide adduct formation in
      electrospray ionization mass spectrometry.
AB  - An equilibrium partitioning model is applied for the first time to the sequential
      formation of 1:1 and then 2:1 adducts between the high explosive cyclo-1,3,5
      trimethylene-2,4,6-trinitramine (RDX) and halide anions fluoride, chloride,
      bromide, and iodide in electrospray ionization interface (ESI) mass spectrometry.
      The equilibrium partitioning model is developed and model calculations are
      presented to demonstrate the generic behavior of the system, which is in
      qualitative agreement with the observed changes in 1:1 (RDX-halide) and 2:1 (RDX
      halide) responses in ESI-MS. The model is successfully applied to the
      experimental data with the use of octanol-water partitioning coefficients to
      predict interior-to-surface partitioning behavior of the complexes in droplets
      formed in the ESI. The data and model suggest that the significantly more
      hydrophobic 2:1 complexes are readily observed in ESI-MS, even though their
      formation constants may be several orders of magnitude less than that of the 1:1
      complex. Structures for RDX-halide 1:1 and 2:1 complexes are proposed based on
      ion-dipole attractions and destabilizing dipole-dipole interactions.

PMID- 16285696
TI  - Characterization of vegetable oils by electrospray ionization mass spectrometry
      fingerprinting: classification, quality, adulteration, and aging.
AB  - An improved approach for the direct infusion electrospray ionization mass
      spectrometry (ESI-MS) analysis of vegetable oils is described. The more polar
      components of the oils, including the fatty acids, are simply extracted with
      methanol/water (1:1) solution and analyzed by direct infusion ESI-MS in both the
      negative and positive ion modes. This fingerprinting analysis was applied to
      genuine samples of olive, soybean, corn, canola, sunflower, and cottonseed oil,
      to admixtures of these oils, and samples of aged soybean oil. ESI-MS fingerprints
      in the positive ion mode of the extracts divide the oils into well-defined
      groups, as confirmed by principal component analysis, whereas ESI-MS fingerprints
      in the negative ion mode clearly differentiate olive oil from the five other
      refined oils. The method is also shown to detect aging and adulteration of
      vegetable oils.

PMID- 16285698
TI  - Ionic liquids as an attractive alternative solvent for thermal lens measurements.
AB  - The use of ionic liquids (ILs) as a solvent for thermal lens measurements has
      been investigated. It was found that ILs provide a better medium for thermal lens
      measurements than water. Specifically, not only the ILs offer at least 20 times
      higher sensitivity than water but that the enhancement can be appropriately
      adjusted by changing either the cation or the anion of the ILs. For example, the
      sensitivity in [BMIm]+[Tf2N]- is approximately 26 times higher than in water. It
      can be increased up to 31 times by changing the anion to [PF6]- (i.e.,
      [BMIm]+[PF6]-) or to 35 times by changing the cation to [OMIm]+ (i.e.,
      [OMIm]+[Tf2N]-). In fact, the sensitivity of thermal lens measurements in ILs is
      comparable to those in volatile organic solvents such as benzene, carbon
      tetrachloride, and hexane. However, the ILs are more desirable as they have
      virtually no vapor pressure. Furthermore, additional sensitivity enhancement (up
      to 42 times higher than that in water) can be achieved by simply adding
      surfactants into the ILs. Based on the thermal conductivity (k) and dn/dT values,
      calculated from the measured thermal time constant tc and thermal lens strength
      theta, it is evident that the observed sensitivity enhancement by the ILs is due
      to their relatively better thermooptical properties. More specifically, the
      enhancement is due not to the relatively modest lowering of the thermal
      conductivity but rather to the substantial increase in their dn/dT values.
      Because of the relationship between dn/dT and drho/dT, it is expected that ILs
      can serve as an attractive and superior solvent not only for thermal lens
      measurements but also for other photothermal and photoacoustic techniques as
      well. Also equally important is the fact that the thermal lens technique in
      particular and photothermal techniques, in general, can offer a unique means to
      determine themooptical and thermal physical properties of the ILs (e.g., thermal
      conductivity, thermal diffusivity, and phase transition temperatures). This type
      of data is currently lacking but is of extreme importance for implementing ILs as
      a solvent in various industrial applications.

PMID- 16285699
TI  - Desorption/ionization fluence thresholds and improved mass spectral consistency
      measured using a flattop laser profile in the bioaerosol mass spectrometry of
      single Bacillus endospores.
AB  - Bioaerosol mass spectrometry is being developed to analyze and identify
      biological aerosols in real time. Mass spectra of individual Bacillus endospores
      were measured with a bipolar aerosol time-of-flight mass spectrometer in which
      molecular desorption and ionization were produced using a single laser pulse from
      a Q-switched, frequency-quadrupled Nd:YAG laser that was modified to have an
      approximately flattop profile. The flattened laser profile allowed the minimum
      fluence required to desorb and ionize significant numbers of ions from single
      aerosol particles to be determined. For Bacillus spores, this threshold had a
      mean value of approximately 1 nJ/microm(2) (0.1 J/cm(2)). Thresholds for
      individual spores, however, could apparently deviate by 20% or more from the
      mean. Threshold distributions for clumps of MS2 bacteriophage and bovine serum
      albumin were subsequently determined. Finally, the flattened profile was observed
      to increase the reproducibility of single-spore mass spectra. This is consistent
      with the general conclusions of our earlier paper on the fluence dependence of
      single-spore mass spectra and is particularly significant because it is expected
      to enable more robust differentiation and identification of single bioaerosol
      particles.

PMID- 16285700
TI  - Top-down proteomics for rapid identification of intact microorganisms.
AB  - We apply MALDI-TOF/TOF mass spectrometry for the rapid and high-confidence
      identification of intact Bacillus spore species. In this method, fragment ion
      spectra of whole (undigested) protein biomarkers are obtained without the need
      for biomarker prefractionation, digestion, separation, and cleanup. Laser-induced
      dissociation (unimolecular decay) of higher mass (>5 kDa) precursor ions in the
      first TOF analyzer is followed by reacceleration and subsequent high-resolution
      mass analysis of the resulting sequence-specific fragments in a reflectron TOF
      analyzer. In-house-developed software compares an experimental MS/MS spectrum
      with in silico-generated tandem mass spectra from all protein sequences,
      contained in a proteome database, with masses within a preset range around the
      precursor ion mass. A p-value, the probability that the observed matches between
      experimental and in silico-generated fragments occur by chance, is computed and
      used to rank the database proteins to identify the most plausible precursor
      protein. By inference, the source microorganism is then identified on the basis
      of the identification of individual, unique protein biomarker(s). As an example,
      intact Bacillus atrophaeus and Bacillus cereus spores, either pure or in
      mixtures, were unambiguously identified by this method after fragmenting and
      identifying individual small, acid-soluble spore proteins that are specific for
      each species. Factors such as experimental mass accuracy and number of detected
      fragment ions, precursor ion charge state, and sequence-specific fragmentation
      have been evaluated with the objective of extending the approach to other
      microorganisms. MALDI-TOF/TOF-MS in a lab setting is an efficient tool for in
      situ confirmation/verification of initial microorganism identification.

PMID- 16285701
TI  - Deposition method for preparing SERS-active gold nanoparticle substrates.
AB  - Surface-enhanced Raman scattering or SERS, discovered some 20 years ago, has
      recently become a promising tool for routine biofluid assays in a clinical
      setting. Many attempts have been made to produce cheap and reproducible SERS
      active substrates. In this study, we report on the fabrication of SERS-active
      substrates through the convective assembly of gold (Au) particles on
      electrostatically charged glass slides. We show that, by a proper control of the
      initial particle concentration in an evaporating Au suspension droplet, it is
      possible to obtain a closely packed colloidal film capable of generating SERS
      activity. Finally, AFM and SERS measurements of the resulting films reveal
      comparability in performance with previous silane-immobilized Au colloidal films.
      The minimum electromagnetic enhancement factor of our films is estimated to be
      about 2 x 10(4).

PMID- 16285702
TI  - ATR-FT-IR membrane-based sensor for integrated microliquid-liquid extraction and
      detection.
AB  - A novel straightforward membrane-based sensor, which uses attenuated total
      reflection Fourier transform infrared (ATR-FT-IR) spectroscopy has been
      developed. The flow cell designed permits the on-line microliquid-liquid
      extraction of the target analyte into a organic solvent layer (OSL), which was
      deposited on the ATR surface using a sequential injection manifold. The aqueous
      and organic phases are separated via a commercial hydrophobic membrane placed on
      the PTFE piece of the cell. The main advantage of the proposed device is that the
      OSL can be created and regenerated in a continuous manner using the automatic
      manifold without opening the cell. The analytes are enriched into the OSL after
      diffusion through the membrane, which excludes the typical absorption bands of
      water. In addition, the behavior of different organic solvents was evaluated in
      order to increase the applicability and versatility of the proposed system.
      Finally, the analytical performance of the design was established for the
      detection and quantitation of Triton X100 in water.

PMID- 16285703
TI  - Patterned solvent delivery and etching for the fabrication of plastic
      microfluidic devices.
AB  - A very simple method for micropatterning flat plastic substrates that can be used
      to build microfluidic devices is demonstrated. Patterned poly(dimethylsiloxane)
      elastomer is used as a template to control the flow path of an etching solvent
      through a channel design to be reproduced on the plastic substrate. The etching
      solvent was a acetone/ethanol mixture for poly(methyl methacrylate) substrates or
      a dimethylformamide/acetone mixture for polystyrene. The method is extremely fast
      in that duplicate plastic substrates can be patterned in just a few minutes each.
      We identified conditions that lead to smooth channel surfaces and characterized
      the rate of etching under these conditions. We determined that, for sufficiently
      short etching times (shallow channel depths), the etch rate is independent of the
      linear flow rate. This is very important since it means that the etch depth is
      approximately constant even in complex channel geometries where there will be a
      wide range of etchant flow rates at different positions in the pattern to be
      reproduced. We also demonstrate that the method can be used to produce channels
      with different depths on the same substrate as well as channels that intersect to
      form a continuous fluid junction. The method provides a nice alternative to
      existing methods to rapidly fabricate microfluidic devices in rigid plastics
      without the need for specialized equipment.

PMID- 16285705
TI  - Injection valve for ultrahigh-pressure liquid chromatography.
AB  - The increased interest in HPLC at elevated pressures, beyond the conventional
      6000 psi (400 bar), has created a demand for injection systems capable of
      withstanding pressures beyond the 20,000 psi (1380 bar). To achieve high
      resolution separations, an appropriate length of columns packed with sub 2-microm
      packing materials, a 30,000-40,000 psi (2070-2760 bar) pressure range is
      desirable. A new air-actuated needle valve injection system rated to withstand
      pressures of up to 40,000 psi (2760 bar) has been evaluated. Under isocratic
      chromatographic conditions, injecting 200 nL and operated at approximately 20,000
      psi (1380 bar), the system showed a peak area reproducibility of approximately
      2.5% RSD, contrasting the 5% RSD of a pressured-balanced injection system
      operated under similar conditions. Programmed for partial loop injections using
      injection times of 300-700 ms (injection volumes in the range of 1-2.5 microL)
      and operated at pressures close to 30,000 psi (2070 bar), the reproducibility in
      peak area for the amounts injected was approximately 1.5% RSD or lower, while an
      injection time of 100 ms resulted in a reproducibility of 3-4% RSD. The new
      injection system did not show any significant carryover, and after thousands of
      injections, the system has not shown sign of wear, loss of pressure during
      injection, or loss in chromatographic performance.

PMID- 16285704
TI  - Suppression of matrix clusters and enhancement of peptide signals in MALDI-TOF
      mass spectrometry using nitrilotriacetic acid.
AB  - Matrix clusters and their alkali metal ion adducts suppress peptide signals in
      the 500-1400 Da range and compromise MALDI-TOF mass spectrometric peptide mass
      fingerprinting and protein identification. Addition of 7 mM nitrilotriacetic acid
      to the matrix solution significantly reduced matrix clusters and increased signal
      to-noise ratio of peptide signals approximately 5 to 20-fold. As a result,
      reliability in the identification of femtomole amounts of proteins based on
      peptide mass fingerprinting and database search was significantly enhanced,
      leading to a higher score and sequence coverage.

PMID- 16285706
TI  - Development of a coordination chemistry-based approach for functional
      supramolecular structures.
AB  - The weak-link approach (WLA) to supramolecular assemblies allows for the design
      of multimetallic two- and three-dimensional arrays, host-guest architectures,
      sensors, catalysts, switches, and signal amplification devices. This Account
      describes the course of our investigations in this area beginning with the
      development of a chemical tool kit of building blocks consisting of multiple
      metals and ligands. These building blocks can be rationally mixed and matched to
      provide structures with a wide range of properties that have been used to develop
      functional supramolecular architectures, including chemical sensors and
      allosteric catalysts.

PMID- 16285707
TI  - Reactions and applications of titanium imido complexes.
AB  - This Account highlights aspects of the reactions and applications of titanium
      imido complexes. Over the past decade in particular, the Ti=NR linkage has been
      shown to couple stoichiometrically with a variety of unsaturated substrates
      including CO(2), carbodiimides, isocyanates, isocyanides, acetonitrile,
      phosphaalkynes, alkynes, alkenes, and allenes. Especially recently, there has
      been much interest in using titanium imides as catalysts for hydroamination and
      olefin polymerization. The advances in these areas are also reviewed.

PMID- 16285708
TI  - Tandem oxidation processes using manganese dioxide: discovery, applications, and
      current studies.
AB  - "One-pot" processes in which alcohol oxidations are combined with further
      elaboration of the carbonyl intermediate are reviewed. Sequential processes are
      briefly discussed, but most attention is centered on tandem processes; that is,
      oxidations carried out in the presence of a nucleophilic trapping agent, rather
      than those in which the trapping agent is added after the oxidation is complete.
      As part of this Account, a comprehensive review of the discovery of tandem
      oxidation processes (TOP) will be given together with applications in alkene
      forming reactions, cyclopropanations, and imine, oxime, amine, and heterocycle
      formation.

PMID- 16285709
TI  - Carbon nanotubes in electron donor-acceptor nanocomposites.
AB  - This Account presents recent advances in the design, synthesis, characterization,
      and potential applications of new hybrid materials based on carbon nanotube and
      electron donors. Fast charge separation and slow charge recombination are
      consistently observed in a variety of composites that contain porphyrin
      derivatives. The ultimate goal of using these systems to prepare practical
      photoelectrochemical devices is discussed, and a cell with a monochromatic
      efficiency of 8.5% conversion of light into current is illustrated.

PMID- 16285710
TI  - Polyhedral oligomeric silsesquioxane nanocomposites: the next generation material
      for biomedical applications.
AB  - The unique properties of nanocomposites have seen them creating the next
      revolution in materials science. Their quantal properties as a result of their
      size have given them unique physical characteristics, previously not possible
      because of classical physical laws. There is now evidence that these may also
      extend into the world of biology and medicine. In this Account, we look at the
      birth of a new generation of silica nanocomposites using polyhedral oligomeric
      silsesquioxanes, a promising nanoscale silica particle with particular use in
      cardiovascular interventional devices.

PMID- 16285711
TI  - Exploring the early steps of amyloid peptide aggregation by computers.
AB  - The assembly of normally soluble proteins into amyloid fibrils is a hallmark of
      neurodegenerative diseases. Because protein aggregation is very complex,
      involving a variety of oligomeric metastable intermediates, the detailed
      aggregation paths and structural characterization of the intermediates remain to
      be determined. Yet, there is strong evidence that these oligomers, which form
      early in the process of fibrillogenesis, are cytotoxic. In this paper, we review
      our current understanding of the underlying factors that promote the aggregation
      of peptides into amyloid fibrils. We focus here on the structural and dynamic
      aspects of the aggregation as observed in state-of-the-art computer simulations
      of amyloid-forming peptides with an emphasis on the activation-relaxation
      technique.

PMID- 16285713
TI  - Role of the Met-Tyr-Trp cross-link in Mycobacterium tuberculosis catalase
      peroxidase (KatG) as revealed by KatG(M255I).
AB  - Catalase-peroxidases (KatGs) are bifunctional enzymes possessing both catalase
      and peroxidase activities. Four crystal structures of different KatGs revealed
      the presence of a novel Met-Tyr-Trp cross-link which has been suggested to impart
      catalatic activity to the KatGs. To decipher the individual roles of the two
      cross-links in the Met-Tyr-Trp adduct, we have focused on recombinant
      Mycobacterium tuberculosis KatG(M255I). UV-visible spectroscopic and mass
      spectrometric studies of the peptide fragments resulting from tryptic digestion
      of KatG(M255I) confirmed the presence of the single Tyr-Trp cross-link, as well
      as a 2e- oxidized form which is postulated to be an intermediate generated during
      Met-Tyr-Trp cross-link formation. KatG(M255I) lacking the Tyr-Trp cross-link was
      also prepared, and incubation with peroxyacetic acid, but not 2-methyl-1-phenyl-2
      propyl hydroperoxide, resulted in complete formation of the Tyr-Trp cross-link. A
      mechanism for Tyr-Trp autocatalytic formation by KatG compound I is proposed from
      these studies. Optical stopped-flow studies with KatG(M255I) were performed,
      allowing characterization of compounds I, II, and III. Interestingly, two
      compound II intermediates were identified: (KatG*)(Por)Fe(III)-OH, where KatG*
      represents a protein-based radical, and oxoferryl (KatG)(Por)Fe(IV)=O. Insight
      into the contributions of the individual Tyr-Trp and Met-Tyr cross-links to
      catalase activity is presented, as is the overall contribution of the Met-Tyr-Trp
      cross-link to the structure-function-spectroscopy relationship and catalase
      peroxidase mechanism in KatG.

PMID- 16285712
TI  - Site-directed fluorescence labeling reveals differences on the R-conformer of
      glucosamine 6-phosphate deaminase of Escherichia coli induced by active or
      allosteric site ligands at steady state.
AB  - Engineered glucosamine 6-phosphate deaminase of Escherichia coli with unique
      reactive cysteines at positions 164 or 206 was created by site-directed
      mutagenesis to monitor the allosteric transition in solution by the fluorescence
      emission of the bimane or dansyl-amidoethyl groups attached to the indicated
      residues. The selection of both positions was due to the differential interaction
      of these residues between T- and R-conformers at the interface of two trimers
      that form the hexameric structure; in the T-conformer, residue 164 or 206
      presents only intrasubunit contacts, but in the R-conformer, new intersubunit
      contacts are established. As in the wild-type enzyme, fluorescent-labeled mutants
      show no modification on the allosteric activation of the K-system, only the kcat
      was reduced to a value of 72 s(-1) (approximately 50% of wild-type). With these
      preparations, conformational changes were detected by the fluorescence emission
      spectra at steady state when the active site or the allosteric site ligands were
      titrated. Despite the similar changes in the fluorescence spectra that were
      correlated with the induction of the R-state, differences were observed at the
      maximal change in the fluorescence spectra and in the relative solvent polarities
      at the positions labeled. These data suggested structural differences in the
      conformation of the R-state when it is induced from the active site or from the
      allosteric site, which is not consistent with the two-state structural model
      proposed by previous crystallographic studies of this enzyme.

PMID- 16285714
TI  - Synaptic complex formation of two retrovirus DNA attachment sites by integrase: a
      fluorescence energy transfer study.
AB  - The integration of retroviral DNA by the viral integrase (IN) into the host
      genome occurs via assembled preintegration complexes (PIC). We investigated this
      assembly process using purified IN and viral DNA oligodeoxynucleotide (ODN)
      substrates (93 bp in length) that were labeled with donor (Cy3) and acceptor
      fluorophores (Cy5). The fluorophores were attached to the 5' 2 bp overhangs of
      the terminal attachment (att) sites recognized by IN. Addition of IN to the assay
      mixture containing the fluorophore-labeled ODN resulted in synaptic complex
      formation at 14 degrees C with significant fluorescence resonance energy transfer
      (FRET) occurring between the fluorophores in close juxtaposition (from
      approximately 15 to 100 A). Subsequent integration assays at 37 degrees C with
      the same ODN (32P-labeled) demonstrated a direct association of a significant
      FRET signal with concerted insertion of the two ODNs into the circular DNA
      target, here termed full-site integration. FRET measurements (deltaF) show that
      IN binds to a particular set of 3' OH recessed substrates (type I) generating
      synaptic complexes capable of full-site integration that, as shown previously,
      exhibit IN mediated protection from DNaseI digestion up to approximately 20 bp
      from the ODN att ends. In contrast, IN also formed complexes with nonspecific DNA
      ends and loss-of-function att end substrates (type II) that had significantly
      lower deltaF values and were not capable of full-site integration, and lacked the
      DNaseI protection properties. The type II category may exemplify what is commonly
      understood as "nonspecific" binding by IN to DNA ends. Two IN mutants that
      exhibited little or no integration activity gave rise to the lower deltaF
      signals. Our FRET analysis provided the first direct physical evidence that IN
      forms synaptic complexes with two DNA att sites in vitro, yielding a complex that
      exhibits properties comparable to that of the PIC.

PMID- 16285715
TI  - Solution structure of the cytoplasmic domain of erythrocyte membrane band 3
      determined by site-directed spin labeling.
AB  - The cytoplasmic domain of the anion exchange protein (cdb3) serves as a critical
      organizing center for protein-protein interactions that stabilize the erythrocyte
      membrane. The structure of the central core of cdb3, determined by X-ray
      crystallography from crystals grown at pH 4.8, revealed a compact dimer for
      residues 55-356 and unresolved N- and C-termini on each monomer [Zhang et al.
      (2000) Blood 96, 2925-2933]. Given that previous studies had suggested a highly
      asymmetric structure for cdb3 and that pH dependent structural transitions of
      cdb3 have been reported, the structure of cdb3 in solution at neutral pH was
      investigated via site-directed spin labeling in combination with conventional
      electron paramagnetic resonance (EPR) and double electron electron resonance
      (DEER) spectroscopies. These studies show that the structure of the central
      compact dimer (residues 55-356) is indistinguishable from the crystal structure
      determined at pH 4.8. N-Terminal residues 1-54 and C-terminal residues 357-379
      are dynamically disordered and show no indications of stable secondary structure.
      These results establish a structural model for cdb3 in solution at neutral pH
      which represents an important next step in characterizing structural details of
      the protein-protein interactions that stabilize the erythrocyte membrane.

PMID- 16285716
TI  - Influence of Trp mutation on native, intermediate, and transition states of goat
      alpha-lactalbumin: an equilibrium and kinetic study.
AB  - Equilibrium circular dichroism and kinetic stopped-flow fluorescence studies on
      the stability and the folding kinetics of a set of Trp to Phe mutants of goat
      alpha-lactalbumin (GLA) were used to characterize the native, intermediate, and
      transition states of these constructs. GLA contains four tryptophan residues,
      three of which, Trp26, Trp104, and Trp118, are located in the alpha-domain, while
      the fourth, Trp60, is located in the beta-domain. Trp26, Trp60, and Trp104 are
      part of a hydrophobic cluster, whereas Trp118 is situated in a more flexible
      region near the C-terminal end of the protein. In each case, the mutation leads
      to a reduction in the overall stability, but only for W26F and W60F is an
      equilibrium intermediate observed in guanidine hydrochloride-induced unfolding
      experiments. In kinetic refolding experiments, however, for all samples a burst
      phase is observed, the amplitude of which depends on the specific mutation.
      Refolding and unfolding kinetics can adequately be described by a sequential
      three-state mechanism. phi value analysis showed that the local structure around
      Trp26, Trp60, and Trp104 is formed in the intermediate and in the transition
      state of the folding reaction, while around Trp118 no persistent native contacts
      are observed. From these findings, we conclude that, although hydrophobicity is a
      major driving force for folding, minor steric changes induced by point mutation
      can considerably influence the overall stability and the folding process of the
      protein.

PMID- 16285717
TI  - Probing lysozyme conformation with light reveals a new folding intermediate.
AB  - A means to control lysozyme conformation with light illumination has been
      developed using the interaction of the protein with a photoresponsive surfactant.
      Upon exposure to the appropriate wavelength of light, the azobenzene surfactant
      undergoes a reversible photoisomerization, with the visible-light (trans) form
      being more hydrophobic than the UV-light (cis) form. As a result, surfactant
      binding to the protein and, thus, protein unfolding, can be tuned with light.
      Small-angle neutron scattering (SANS) measurements were used to provide detailed
      information of the protein conformation in solution. Shape-reconstruction methods
      applied to the SANS data indicate that under visible light the protein exhibits a
      native-like form at low surfactant concentrations, a partially swollen form at
      intermediate concentrations, and a swollen/unfolded form at higher surfactant
      concentrations. Furthermore, the SANS data combined with FT-IR spectroscopic
      analysis of the protein secondary structure reveal that unfolding occurs
      primarily in the alpha domain of lysozyme, while the beta domain remains
      relatively intact. Thus, the surfactant-unfolded intermediate of lysozyme appears
      to be a separate structure than the well-known alpha-domain intermediate of
      lysozyme that contains a folded alpha domain and unfolded beta domain. Because
      the interactions between the photosurfactant and protein can be tuned with light,
      illumination with UV light returns the protein to a native-like conformation.
      Fluorescence emission data of the nonpolar probe Nile red indicate that
      hydrophobic domains become available for probe partitioning in surfactant-protein
      solutions under visible light, while the availability of these hydrophobic
      domains to the probe decrease under UV light. Dynamic light scattering and UV-vis
      spectroscopic measurements further confirm the shape-reconstruction findings and
      reveal three discrete conformations of lysozyme. The results clearly demonstrate
      that visible light causes a greater degree of lysozyme swelling than UV light,
      thus allowing for the protein conformation to be controlled with light.

PMID- 16285718
TI  - Isolation and characterization of the B-cell marker CD20.
AB  - The integral membrane protein CD20 has been identified as an important
      therapeutic target in the treatment of non-Hodgkin's lymphoma (NHL). CD20 binding
      of many antibodies including the therapeutic antibody, rituximab, has been shown
      to be critically dependent upon the conformation of a loop structure between the
      third and fourth helical transmembrane regions. In this work, human and murine
      CD20 proteins expressed in Escherichia coli are shown to be localized with the
      cell membrane and are purified in nondenaturing detergent solutions. The purified
      human and murine CD20 proteins have a substantial helical structure as measured
      by circular dichroism spectroscopy. Only small changes in the secondary structure
      are observed following the reduction of CD20, with the addition of SDS, or after
      heating. The rituximab antibody is shown to bind to purified human CD20 with
      nanomolar affinity. Rituximab binding is abolished by reduction and alkylation of
      CD20, with data consistent with the proposed antibody epitope being within the
      disulfide-bonded loop formed between cysteine residues 167 and 183. Disulfide
      bond-dependent antibody binding is partially recovered following reoxidation of
      reduced CD20. Antibody binding is unaffected by mutations of cysteines proposed
      to be in the intracellular domain of CD20. The affinities of intact rituximab and
      its Fab fragment to the isolated and purified CD20 are similar to the observed
      affinity of rituximab Fab for CD20 on the surface of B cells. However, the intact
      rituximab antibody shows much higher affinity for CD20 on B cells. This suggests
      that B cells display CD20 in such a way that allows for marked avidity effects to
      be observed, perhaps through cross-linking of CD20 monomers into lipid rafts,
      which limits receptor diffusion in the membrane. Such cross-linking may play a
      role in partitioning CD20 into lipid rafts and in enhancing antibody-dependent B
      cell depletion activities of rituximab and other therapeutic anti-CD20
      antibodies.

PMID- 16285719
TI  - Strongly hydrogen-bonded water molecule present near the retinal chromophore of
      Leptosphaeria rhodopsin, the bacteriorhodopsin-like proton pump from a eukaryote.
AB  - Leptosphaeria rhodopsin (LR) is an archaeal-type rhodopsin found in fungi, and is
      the first light-driven proton-pumping retinal protein from eukaryotes. LR pumps
      protons in a manner similar to that of bacteriorhodopsin (BR), a light-driven
      proton pump of haloarchaea. The amino acid sequence of LR is more homologous to
      that of Neurospora rhodopsin (NR) than BR, whereas NR has no proton-pumping
      activity. These facts raise the question of how the proton-pumping function is
      achieved. In this paper, we studied structural changes of LR following the
      retinal photoisomerization by means of low-temperature Fourier transform infrared
      (FTIR) spectroscopy, and compared the obtained spectra with those for BR and NR.
      While the light-induced photoisomerization from the all-trans to 13-cis form was
      commonly observed among LR, BR, and NR, we found that the structural changes of
      LR are closer to those of BR than to those of NR in terms of detailed vibrational
      bands of retinal and protein. The most prominent difference was seen for the
      water O-D stretching vibrations (measured in D2O). LR exhibits an O-D stretch of
      water at 2257 cm(-1), indicating the presence of a strongly hydrogen-bonded water
      molecule. Such strongly hydrogen-bonded water molecules (O-D stretch at <2400 cm(
      1)) were observed for BR, but not for NR. Comprehensive studies of BR mutants and
      archaeal rhodopsins have revealed that strongly hydrogen-bonded water molecules
      are found only in the proteins exhibiting proton-pumping activity, suggesting
      that strongly hydrogen-bonded water molecules and transient weakening of their
      binding are essential for the proton-pumping function of rhodopsins. This
      observation for LR provided additional experimental evidence of the correlation
      between strongly hydrogen-bonded water molecules and proton-pumping activity of
      archaeal rhodopsins.

PMID- 16285720
TI  - Electronic structure studies of the adenosylcobalamin cofactor in glutamate
      mutase.
AB  - Glutamate mutase (GM) is a cobalamin-dependent enzyme that catalyzes the
      reversible interconversion of L-glutamate and L-threo-3-methylaspartate via a
      radical-based mechanism. To initiate catalysis, the 5'-deoxyadenosylcobalamin
      (AdoCbl) cofactor's Co-C bond is cleaved homolytically to generate an adenosyl
      radical and Co2+ Cbl. In this work, we employed a combination of spectroscopic
      and computational tools to evaluate possible mechanisms by which the Co-C bond is
      activated for homolysis. Minimal perturbations to the electronic absorption
      (Abs), circular dichroism (CD), and magnetic CD (MCD) spectra of AdoCbl are
      observed upon formation of holoenzyme, even in the presence of substrate (or a
      substrate analogue), indicating that destabilization of the Co3+ Cbl "ground
      state" is an unlikely mechanism for Co-C bond activation. In contrast, striking
      alterations are observed in the spectroscopic data of the post-homolysis product
      Co2+ Cbl when bound to glutamate mutase in the presence of substrate (or a
      substrate analogue) as compared to unbound Co2+ Cbl. These enzymatic
      perturbations appear to most strongly affect the metal-to-ligand charge-transfer
      transitions of Co2+ Cbl, suggesting that the cofactor/active-site interactions
      give rise to a fairly uniform stabilization of the Co 3d orbitals. Remarkable
      similarities between the results obtained in this study and those reported
      previously for the related Cbl-dependent isomerase methylmalonyl-CoA mutase
      indicate that a common mechanism by which the cofactor's Co-C bond is activated
      for homolytic cleavage may be operative for all base-off/His-on Cbl-dependent
      isomerases.

PMID- 16285721
TI  - Structural dynamics of the manganese-stabilizing protein-effect of pH, calcium,
      and manganese.
AB  - The photosystem-II-associated 33-kDa extrinsic manganese-stabilizing protein is
      found in all oxygen-evolving organisms. In this paper, we show that this protein
      undergoes pH-induced conformational changes in the physiological pH range. At a
      neutral pH of 7.2, the hydrophobic amino acid residues that are most likely
      located inside the beta barrel are "closed" and the protein binds neither Mn2+
      nor Ca2+ ions. When the protein is transferred to a solution with a slightly
      acidic pH of 5.7, hydrophobic amino acid residues become exposed to the
      surrounding medium, enabling them to bind the fluorescent probe 8,1-ANS. At this
      pH-induced open state, Mn2+ and Ca2+ bind to the manganese-stabilizing protein.
      The pH values used in this study, 7.2 and 5.7, are typical of the pH found in the
      thylakoid lumen in the dark and light, respectively. A model is presented in
      which the manganese-stabilizing protein undergoes a pH-dependent conformational
      change that in turn influences its capacity to bind calcium and manganese. In
      this model, the proton-dependent conformational changes of the tertiary structure
      of the manganese-stabilizing protein are of functional relevance for the
      regulation of substrate (water) delivery to and product (proton) release from the
      water-oxidizing complex by forming a proton-sensing proton-transport pathway.

PMID- 16285722
TI  - The substrate-bound type 2 copper site of nitrite reductase: the nitrogen
      hyperfine coupling of nitrite revealed by pulsed EPR.
AB  - A pulsed electron paramagnetic resonance study has been performed on the type 2
      copper site of nitrite reductase (NiR) from Alcaligenes faecalis. The H145A
      mutant, in which histidine 145 is replaced by alanine, was studied by ESEEM and
      HYSCORE experiments at 9 GHz on frozen solutions. This mutant contains a reduced
      type 1 copper site which allowed a selective investigation of the type 2 site of
      H145A and of its nitrite-bound form H145A (NO2(-)). The experiments yielded
      hyperfine and quadrupole parameters of the remote nitrogens of two of the
      histidines in the type 2 copper site of the protein and revealed the changes of
      these values induced by substrate binding (14NO2(-) and 15NO2(-)). The HYSCORE
      experiments displayed a signal of 15NO2(-) bound to H145A, from which hyperfine
      parameters of the nitrite nitrogen were estimated. The small isotropic hyperfine
      coupling, 0.36 MHz, of the nitrite nitrogen (14N) suggests that the substrate
      binds in an axial position to the copper in the type 2 site and that the
      molecular orbital containing the unpaired electron extends onto the substrate.
      This and other changes in the EPR parameters occurring after nitrite binding
      suggest a change in electronic structure of the site, which most likely prepares
      the site for the catalytic reaction. We propose that this change is essential for
      the reaction to occur.

PMID- 16285724
TI  - Association of the 17-kDa extrinsic protein with photosystem II in higher plants.
AB  - The structural association of the spinach 17-kDa extrinsic protein of photosystem
      II with other extrinsic and membrane-bound components of the photosystem was
      investigated by labeling the 17-kDa extrinsic protein with the amino-group
      specific reagent N-hydroxysuccinimidobiotin both on intact photosystem II
      membranes or as a free protein in solution. After isolation of the biotinylated
      molecules, the modified 17-kDa proteins were allowed to rebind to photosystem II
      membranes which were depleted of the 17-kDa component. Differential binding of
      the protein biotinylated in solution compared to unmodified 17-kDa protein or 17
      kDa protein modified on PS II membranes was observed. This indicated possible
      steric or ionic interference because of biotinylated lysyl residues present on
      the protein modified in solution. Biotinylated sites on the different modified 17
      kDa proteins were identified by trypsin and Staphylococcus V8 protease digestion,
      followed by affinity chromatography enrichment of the biotinylated peptides and
      analysis of the peptide fragment mixture by nanospray liquid chromatography
      tandem mass spectrometry. Four lysyl residues that were modified when the protein
      was biotinylated in solution were not biotinylated when the protein was modified
      on the PS II membrane (90K, 96K, 101K, and 102K). These residues appear to
      identify a protein domain involved in the interaction of the 17-kDa protein with
      the other components of the photosystem.

PMID- 16285725
TI  - Exploring the binding conformations of bulkier dipeptide amide inhibitors in
      constitutive nitric oxide synthases.
AB  - A series of L-nitroarginine-based dipeptide inhibitors are highly selective for
      neuronal nitric oxide synthase (nNOS) over the endothelial isoform (eNOS).
      Crystal structures of these dipeptides bound to both isoforms revealed two
      different conformations, curled in nNOS and extended in eNOS, corresponding to
      higher and lower binding affinity to the two isoforms, respectively. In previous
      studies we found that the primary reason for selectivity is that Asp597 in nNOS,
      which is Asn368 in eNOS, provides greater electrostatic stabilization in the
      inhibitor complex. While this is the case for smaller dipeptide inhibitors,
      electrostatic stabilization may no longer be the sole determinant for isoform
      selectivity with bulkier dipeptide inhibitors. Another residue farther away from
      the active site, Met336 in nNOS (Val106 in eNOS), is in contact with bulkier
      dipeptide inhibitors. Double mutants were made to exchange the D597/M336 pair in
      nNOS with N368/V106 in eNOS. Here we report crystal structures and inhibition
      constants for bulkier dipeptide inhibitors bound to nNOS and eNOS that illustrate
      the important role played by residues near the entry to the active site in
      isoform selective inhibition.

PMID- 16285723
TI  - Multiple roles of a conserved GAF domain tyrosine residue in cyanobacterial and
      plant phytochromes.
AB  - The phytochrome family of red/far-red photoreceptors has been optimized to
      support photochemical isomerization of a bound bilin chromophore, a process that
      triggers a conformational change and modulates biochemical output from the
      surrounding protein scaffold. Recent studies have established that the efficiency
      of this photochemical process is profoundly altered by mutation of a conserved
      tyrosine residue (Tyr176) within the bilin-binding GAF domain of the
      cyanobacterial phytochrome Cph1 [Fischer, A. J., and Lagarias, J. C. (2004)
      Harnessing phytochrome's glowing potential, Proc. Natl. Acad. Sci. U.S.A. 101,
      17334-17339]. Here, we show that the equivalent mutation in plant phytochromes
      behaves similarly, indicating that the function of this tyrosine in the primary
      photochemical mechanism is conserved. Saturation mutagenesis of Tyr176 in Cph1
      establishes that no other residue can support comparably efficient
      photoisomerization. The spectroscopic consequences of Tyr176 mutations also
      reveal that Tyr176 regulates the conversion of the porphyrin-like conformation of
      the bilin precursor to a more extended conformation. The porphyrin-binding
      ability of the Tyr176Arg mutant protein indicates that Tyr176 also regulates the
      ligand-binding specificity of apophytochrome. On the basis of the hydrogen
      bonding ability of Tyr176 substitutions that support the nonphotochemical C15
      Z,syn to C15-Z,anti interconversion, we propose that Tyr176 orients the carboxyl
      side chain of a conserved acidic residue to stabilize protonation of the bilin
      chromophore. A homology model of the GAF domain of Cph1 predicts a C5-Z,syn, C10
      Z,syn, C15-Z,anti configuration for the chromophore and implicates Glu189 as the
      proposed acidic residue stabilizing the extended conformation, an interpretation
      consistent with site-directed mutagenesis of this conserved acidic residue.

PMID- 16285726
TI  - A thymine isostere in the templating position disrupts assembly of the closed DNA
      polymerase beta ternary complex.
AB  - The high fidelity of the DNA polymerization process is critically important for
      the stability of the cellular genome. The role of template and incoming
      nucleotide base pairing in polymerase fidelity has recently been explored by the
      use of nucleotide isosteres, which preserve the steric but not the electronic
      properties of the corresponding bases. The DNA repair enzyme, DNA polymerase beta
      (Pol beta), is among the most discriminating, being inactive when the thymine
      isostere difluorotoluene (DFT) is present in the templating base position. To
      explore the physical basis for this inactivity, we have performed NMR studies on
      [methyl-13C]methionine-labeled Pol beta complexed with double-hairpin DNA, used
      to model the gapped nucleotide substrate, and having either a thymine or a DFT
      isostere at the templating base position. The six methionine residues distributed
      throughout the enzyme provide useful conformational probes of the lyase and
      polymerase domains and subdomains. Analysis of the proton shift of Met282 that
      results from formation of an abortive Pol beta-gapped DNA-dATP complex is
      consistent with an open to closed conformational change of the enzyme predicted
      from crystal structures. In contrast, the same resonance is nearly unshifted when
      a ternary complex is formed from dATP and gapped DNA in which a DFT isostere
      replaces thymine at the templating base position. Alternatively, the resonances
      of Met191 and Met155, located in the catalytic subdomain, show perturbations upon
      formation of the abortive ternary complex, which are qualitatively similar, but
      significantly weaker, than the changes observed when thymine is present at the
      templating base position. The changes in the Met155 and Met191 methyl resonances
      are in fact more similar to those observed in the binary Pol beta-dATP complex.
      These studies demonstrate that the block in catalysis is directly related to the
      absence of the set of conformational transitions that include the "open" to
      "closed" transition monitored by Met282.

PMID- 16285727
TI  - Role of loop residues and cations on the formation and stability of dimeric DNA G
      quadruplexes.
AB  - Formation of guanine-quadruplexes by four DNA oligonucleotides with common
      sequence dG4-loop-dG4 has been studied by a combination of NMR and UV
      spectroscopy. The loops consisted of 1',2'-dideoxyribose, propanediol,
      hexaethylene glycol, and thymine residues. The comparison of data on modified and
      parent oligonucleotides gave insight into the role of loop residues on formation
      and stability of dimeric G-quadruplexes. All modified oligonucleotides fold into
      dimeric fold-back G-quadruplexes in the presence of sodium ions. Multiple
      structures form in the presence of potassium and ammonium ions, which is in
      contrast to the parent oligonucleotide with dT4 loop. 15N-filtered 1H NMR spectra
      demonstrate that all studied G-quadruplexes exhibit three 15NH4(+) ion binding
      sites. Topology of intermolecular G-quadruplexes was evaluated by NMR
      measurements and diffusion experiments. The spherical, prolate-ellipsoid and
      symmetric cylinder models were used to interpret experimental translational
      diffusion constants in terms of diameters and lengths of unfolded
      oligonucleotides and their respective G-quadruplexes. UV melting and annealing
      curves show that oligonucleotides with non-nucleosidic loop residues fold faster,
      exhibit no hysteresis, and are less stable than dimeric d(G4T4G4)2 which can be
      attributed to the absence of H-bonds, stacking between loop residues and the
      outer G-quartets as well as cation-pi interactions. Oligonucleotide consisting of
      hexaethylene glycol linkage with only two phosphate groups in the loop exhibits
      higher melting temperature and more negative deltaH(o) and deltaG(o) values than
      oligonucleotides with four 1',2'-dideoxyribose or propanediol residues.

PMID- 16285728
TI  - NMR analyses of the activation of the Arp2/3 complex by neuronal Wiskott-Aldrich
      syndrome protein.
AB  - The VCA domain of the neuronal Wiskott-Aldrich syndrome protein (N-WASP) is a
      potent activator of the Arp2/3 complex, a 240 kDa heteroheptameric actin
      nucleating assembly. We used site-directed spin labeling of N-WASP peptides in
      conjunction with methyl-TROSY spectra of the intact, selectively labeled Arp2/3
      complex to identify regions of the VCA that are proximal to the ARPC3 subunit of
      the assembly. We also cross-linked CA peptides to the Arp3, Arp2, ARPC1, and
      ARPC3 subunits. The combined data suggest that the extreme C-terminus of the A
      region and the C-terminus of the C region of N-WASP are proximal to ARPC3. These
      results have implications for the mechanism of Arp2/3 complex activation by VCA
      peptides. This study also demonstrates the utility of NMR spectroscopy for
      studying ligand binding events in large, asymmetric, macromolecular assemblies.

PMID- 16285729
TI  - Acidic region tyrosines provide access points for allosteric activation of the
      autoinhibited Vav1 Dbl homology domain.
AB  - Autoinhibited proteins serve key roles in many signal transduction pathways, and
      therefore proper regulation of these proteins is critical for normal cellular
      function. Proto-oncogene Vav1 is an autoinhibited guanine nucleotide exchange
      factor (GEF) for Rho family GTPases. The core autoinhibitory module of Vav1
      consists of the catalytic Dbl homology (DH) domain bound through its active site
      to an alpha helix centered about Tyr174 in the Acidic (Ac) region of the protein.
      Phosphorylation of Tyr174 and two other tyrosines in the Ac region, Tyr142 and
      Tyr160, relieves autoinhibition and activates the catalytic DH domain. In this
      study, we use biochemical and structural analyses of the Vav1 Ac and DH domains
      to examine the kinetic and thermodynamic properties of Vav1 activation by the Src
      family kinase, Lck, and the role of the Lck SH2 domain in this process. We find
      that in the Ac-DH fragment of Vav1, Tyr174, but not Tyr142 or Tyr160, is
      protected from phosphorylation by interactions with the DH domain. Binding of the
      Lck SH2 domain to phosphorylated Tyr142 increases kcat/KM for Tyr174 by 4-fold,
      likely because the kinase domain can act on the substrate effectively in an
      intramolecular fashion. These studies of the autoinhibited Ac-DH module provide
      the foundation for a quantitative structural and thermodynamic understanding of
      the regulation of full length Vav1. Moreover, kinetic pathways involving initial
      interactions with exposed sites or "access points", as observed here for Vav1,
      may be generally important in the regulation of many autoinhibited proteins.

PMID- 16285730
TI  - Structure and assembly of the heterotrimeric and homotrimeric C-propeptides of
      type I collagen: significance of the alpha2(I) chain.
AB  - Assembly of the type I procollagen molecule begins with interactions among the C
      pro alpha1(I) and C-pro alpha2(I) domains. The C-propeptide domains themselves
      have subdomains of distinct structures. The important questions are where chain
      association begins and the basis of the chain selectivity which leads to the
      preferential formation of the [C-pro alpha1(I)]2[C-pro alpha2(I)] heterotrimer.
      These questions are addressed by energy minimization modeling of the individual C
      propeptide structures, study of their docking interactions, and comparison of the
      heterotrimeric and homotrimeric C-pro structures and stability. The comparisons
      show the remarkable impact of the C-pro alpha2 chain on the structure of the
      assembled trimeric C-propeptide. In the modeling, the three chains were anchored
      and registered by a short C-terminal collagen triple-helical segment followed by
      the C-telopeptides in their docked conformation, and then the remaining C
      propeptide chains were allowed to interact and dock. Surprisingly, propeptide
      trimerization did not proceed through the previously proposed N-terminal
      "oligomerization domain" of the C-propeptide [McAlinden et al. (2003) J. Biol.
      Chem. 278, 42200] but rather in the most C-terminal domains of type I procollagen
      chains. Molecular dynamics showed heterotrimer assembly to begin with dimer
      formation between globular G2alpha2 and the G2alpha1(2) domains followed by
      trimerization at the G1 domains. Assembly initiation in the putative
      oligomerization coiled-coil domain is not possible because of the Pro residues at
      positions 3, 7, and 11 at the N-terminus of the alpha2 C-propeptide chain. To
      confirm the computations and proposed assembly pathway, the G2alpha1 and G2alpha2
      domains were prepared recombinantly as the maltose binding protein constructs,
      and their interactions were studied by dynamic light scattering and gel
      filtration chromatography. Under the conditions examined MBP remained as monomer,
      MBP-G2alpha1 and MBP-G2alpha2 alone formed dimers, but a 2:1 mixture of MBP
      G2alpha1 and MBP-G2alpha2 favored trimer formation. Thus, the C-terminal globular
      domains (G2) of the type I collagen C-propeptides play a crucial role in the
      initiation of intermolecular assembly and heterotrimer selectivity.

PMID- 16285731
TI  - Kinetic and structural characterization of phosphofructokinase from Lactobacillus
      bulgaricus.
AB  - Phosphofructokinase from Lactobacillus delbrueckii subspecies bulgaricus (LbPFK)
      has been reported to be a nonallosteric analogue of phosphofructokinase from
      Escherichia coli at pH 8.2 [Le Bras et al. (1991) Eur. J. Biochem. 198, 683-687].
      A reexamination of the kinetics of this enzyme shows LbPFK to have limited
      binding affinity toward the allosteric ligands, MgADP and PEP, with dissociation
      constants of approximately 20 mM for both. Their allosteric effects are observed
      only at high concentrations of these ligands, with both exhibiting inhibitory
      effects on substrate binding. No pH dependence was observed for the binding and
      the influence of MgADP and PEP on the enzyme. To attempt to explain these
      results, the crystal structure of LbPFK was solved using molecular replacement to
      1.86 A resolution. A comparative study of the LbPFK structure with that of
      phosphofructokinases from E. coli (EcPFK) and Bacillus stearothermophilus (BsPFK)
      reveals a structure with conserved fold and substrate binding site. The effector
      binding site, however, shows many differences that could explain the observed
      decreases in binding affinity for MgADP and PEP in LbPFK as compared to the other
      two enzymes.

PMID- 16285732
TI  - Cdk2: a genuine protein kinase client of Hsp90 and Cdc37.
AB  - Hsp90 and its cochaperone Cdc37 cooperate to provide requisite support to
      numerous protein kinases involved in cellular signal transduction. In this
      report, we studied the interactions of Hsp90 and Cdc37 with the cyclin-dependent
      kinase, Cdk2. Treatment of K562 cells with the Hsp90 inhibitor, geldanamycin,
      caused a 75% reduction in Cdk2 levels and reduced the levels of its activating
      kinase, Cdk7, by more than 60%, suggesting that both of these kinases may be
      Hsp90 clients. Using classical pull-down assays and the Hsp90 inhibitory agents
      geldanamycin and molybdate, Cdk2 is shown to be a genuine client of the Hsp90
      chaperone complex. Subsequently, pull-down assays directed at helix alphaC of
      Cdk2 are shown to disrupt Hsp90 and Cdc37 binding and explain the initial
      difficulties in demonstrating these interactions. Mutant constructs containing
      deletions of secondary structural elements from the N- and C-termini of Cdk2 were
      prepared and assayed for their ability to coadsorb Hsp90 and Cdc37 in a salt
      stable high-affinity manner with and without the addition of molybdate.
      Consistent with similar work done with the cyclin-dependent kinase relative Cdk4,
      the presence of the G-box motif of Cdk2 was shown to be critical for Cdc37
      binding, whereas consistent with work done with the Src-family tyrosine kinase
      Lck, the presence of helix alphaC and the stabilization of helix alphaE were
      shown to be needed for Hsp90 binding.

PMID- 16285733
TI  - Phosphatidylserine membrane domain clustering induced by annexin A2/S100A10
      heterotetramer.
AB  - By means of scanning force and fluorescence microscopy of artificial membranes
      immobilized on mica surfaces, the lateral organization of the annexin A2/S100A10
      heterotetramer (annexin A2t) and its influence on the lateral organization of the
      lipids within the membrane have been elucidated. Planar lipid bilayers composed
      of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/1-palmitoyl-2-oleoyl
      sn-glycero-3-phosphoserine (POPS) were prepared on atomically flat mica surfaces
      by the spreading of unilamellar vesicles. Fluorescence images of fluorescently
      labeled annexin A2t and scanning force microscopy images of nonlabeled protein
      bound to POPC/POPS bilayers show the formation of micrometer-sized lateral
      protein domains in the presence of 1 mM CaCl2. By means of scanning force
      microscopy, not only protein domains became discernible but also small membrane
      domains, which were attributed to POPS-enriched areas. A depletion of these POPS
      domains was observed in the vicinity of annexin A2t protein domains. These
      results indicate that annexin A2t is a peripheral membrane-binding complex
      capable of inducing lipid segregation.

PMID- 16285734
TI  - Intersubunit interaction induced by subunit rearrangement is essential for the
      catalytic activity of the hyperthermophilic glutamate dehydrogenase from
      Pyrobaculum islandicum.
AB  - The specific activity of recombinant Pyrobaculum islandicum glutamate
      dehydrogenase (pis-GDH) expressed in Escherichia coli is much lower than that of
      the native enzyme. However, when the recombinant enzyme is heated at 90 degrees C
      or exposed to 5 M urea, the activity increases to a level comparable to that of
      the native enzyme. Small-angle X-ray scattering measurements revealed that the
      radius of gyration (R(g,z)) of the hexameric recombinant enzyme was reduced to 47
      A from 55 A by either heat or urea, and that the final structure of the active
      enzyme is the same irrespective of the mechanism of activation. Activation was
      accompanied by a shift in the peaks of the Kratky plot, though the molecular mass
      of the enzyme was unchanged. The activation-induced decline in R(g,z) followed
      first-order kinetics, indicating that activation of the enzyme involved a
      transition between two states, which was confirmed by singular-value
      decomposition analysis. When the low-resolution structure of the recombinant
      enzyme was restored using ab initio modeling, we found it to possess no point
      symmetry, whereas the heat-activated enzyme possessed 32-point symmetry. In
      addition, a marked increase in the fluorescence emission was observed with
      addition of ANS to the inactive recombinant enzyme but not the active forms,
      indicating that upon activation hydrophobic residues on the surface of the
      recombinant protein moved to the interior. Taken together, these data strongly
      suggest that subunit rearrangement, i.e., a change in the quaternary structure of
      the hexameric recombinant pis-GDH, is essential for activation of the enzyme.

PMID- 16285735
TI  - Peptide specificity of protein prenyltransferases is determined mainly by
      reactivity rather than binding affinity.
AB  - Protein farnesyltransferase (FTase) and protein geranylgeranyltransferase type I
      (GGTase I) catalyze the attachment of lipid groups from farnesyl diphosphate and
      geranylgeranyl diphosphate, respectively, to a cysteine near the C-terminus of
      protein substrates. FTase and GGTase I modify several important signaling and
      regulatory proteins with C-terminal CaaX sequences ("C" refers to the cysteine
      residue that becomes prenylated, "a" refers to any aliphatic amino acid, and "X"
      refers to any amino acid). In the CaaX paradigm, the C-terminal X-residue of the
      protein/peptide confers specificity for FTase or GGTase I. However, some
      proteins, such as K-Ras, RhoB, and TC21, are substrates for both FTase and GGTase
      I. Here we demonstrate that the C-terminal amino acid affects the binding
      affinity of K-Ras4B-derived hexapeptides (TKCVIX) to FTase and GGTase I modestly.
      In contrast, reactivity, as indicated by transient and steady-state kinetics,
      varies significantly and correlates with hydrophobicity, volume, and structure of
      the C-terminal amino acid. The reactivity of FTase decreases as the
      hydrophobicity of the C-terminal amino acid increases whereas the reactivity of
      GGTase I increases with the hydrophobicity of the X-group. Therefore, the
      hydrophobicity, as well as the structure of the X-group, determines whether
      peptides are specific for farnesylation, geranylgeranylation, or dual
      prenylation.

PMID- 16285736
TI  - Upstream polybasic region in peptides enhances dual specificity for prenylation
      by both farnesyltransferase and geranylgeranyltransferase type I.
AB  - Protein farnesyltransferase (FTase) and protein geranylgeranyltransferase type I
      (GGTase I) catalyze the attachment of a farnesyl or geranylgeranyl lipid,
      respectively, near the C-terminus of their protein substrates. FTase and GGTase I
      differ in both their substrate specificity and magnesium dependence, where the
      activity of FTase, but not GGTase I, is activated by magnesium. Many protein
      substrates of these enzymes contain an upstream polybasic region that is proposed
      to increase the affinity of the substrate and aid in plasma membrane association.
      Here, we demonstrate that the addition of an upstream polybasic region to a
      peptide substrate enhances the binding affinity of FTase approximately 4-fold for
      the peptide but diminishes the catalytic efficiency of the reaction, reflected by
      decreases in both the prenylation rate constant and kcat/KM. Specifically, the
      prenylation rate constant decreases 7-fold at 5 mM MgCl2 for the peptide
      KKKSKTKCVIM (C-terminal sequence of K-Ras4B) in comparison to TKCVIM. This
      decrease is accompanied by an alteration in the dependence on magnesium, as the
      K(Mg) increases from 2.2 +/- 0.1 mM for TKCVIM to 11.5 +/- 0.1 mM for
      KKKSKTKCVIM. The presence of an upstream polybasic region does not significantly
      affect GGTase I-catalyzed reactions, as only minimal changes are seen in Kd,
      kcat/KM, and k(chem) values. Thus, the presence of an upstream polybasic region
      enhances the dual prenylation of these substrates, by decreasing the catalytic
      efficiency of farnesylation catalyzed by FTase to a level comparable to that of
      geranylgeranylation catalyzed by GGTase I.

PMID- 16285737
TI  - Transient state kinetic studies of the MutT-catalyzed nucleoside triphosphate
      pyrophosphohydrolase reaction.
AB  - The MutT pyrophosphohydrolase, in the presence of Mg2+, catalyzes the hydrolysis
      of nucleoside triphosphates by nucleophilic substitution at Pbeta, to yield the
      nucleotide and PP(i). The best substrate for MutT is the mutagenic 8-oxo-dGTP, on
      the basis of its Km being 540-fold lower than that of dGTP. Product inhibition
      studies have led to a proposed uni-bi-iso kinetic mechanism, in which PP(i)
      dissociates first from the enzyme-product complex (k3), followed by NMP (k4),
      leaving a product-binding form of the enzyme (F) which converts to the substrate
      binding form (E) in a partially rate-limiting step (k5) [Saraswat, V., et al.
      (2002) Biochemistry 41, 15566-15577]. Single- and multiple-turnover kinetic
      studies of the hydrolysis of dGTP and 8-oxo-dGTP and global fitting of the data
      to this mechanism have yielded all of the nine rate constants. Consistent with an
      "iso" mechanism, single-turnover studies with dGTP and 8-oxo-dGTP hydrolysis
      showed slow apparent second-order rate constants for substrate binding similar to
      their kcat/Km values, but well below the diffusion limit (approximately 10(9) M(
      1) s(-1)): k(on)app = 7.2 x 10(4) M(-1) s(-1) for dGTP and k(on)app = 2.8 x 10(7)
      M(-1) s(-1) for 8-oxo-dGTP. These low k(on)app values are fitted by assuming a
      slow iso step (k5 = 12.1 s(-1)) followed by fast rate constants for substrate
      binding: k1 = 1.9 x 10(6) M(-1) s(-1) for dGTP and k1 = 0.75 x 10(9) M(-1) s(-1)
      for 8-oxo-dGTP (the latter near the diffusion limit). With dGTP as the substrate,
      replacing Mg2+ with Mn2+ does not change k1, consistent with the formation of a
      second-sphere MutT-M2+-(H2O)-dGTP complex, but slows the iso step (k5) 5.8-fold,
      and its reverse (k(-5)) 25-fold, suggesting that the iso step involves a change
      in metal coordination, likely the dissociation of Glu-53 from the enzyme-bound
      metal so that it can function as the general base. Multiple-turnover studies with
      dGTP and 8-oxo-dGTP show bursts of product formation, indicating partially rate
      limiting steps following the chemical step (k2). With dGTP, the slow steps are
      the chemical step (k2 = 10.7 s(-1)) and the iso step (k5 = 12.1 s(-1)). With 8
      oxo-dGTP, the slow steps are the release of the 8-oxo-dGMP product (k4 = 3.9 s(
      1)) and the iso step (k5 = 12.1 s(-1)), while the chemical step is fast (k2 =
      32.3 s(-1)). The transient kinetic studies are generally consistent with the
      steady state kcat and Km values. Comparison of rate constants and free energy
      diagrams indicate that 8-oxo-dGTP, at low concentrations, is a better substrate
      than dGTP because it binds to MutT 395-fold faster, dissociates 46-fold slower,
      and has a 3.0-fold faster chemical step. The true dissociation constants (KD) of
      the substrates from the E-form of MutT, which can now be obtained from k(-1)/k1,
      are 3.5 nM for 8-oxo-dGTP and 62 microM for dGTP, indicating that 8-oxo-dGTP
      binds 1.8 x 10(4)-fold tighter than dGTP, corresponding to a 5.8 kcal/mol lower
      free energy of binding.

PMID- 16285738
TI  - Susceptibility of amyloid beta peptide degrading enzymes to oxidative damage: a
      potential Alzheimer's disease spiral.
AB  - Insulysin (IDE) and neprilysin (NEP) were found to be inactivated by oxidation
      with hydrogen peroxide, an iron-ascorbate oxidation system, and by treatment with
      2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). In each case reaction led
      to the introduction of protein carbonyl groups as judged by reaction with 2,4
      dintrophenylhydrazine. IDE was inactivated by reaction with 4-hydroxy-2-nonenal
      (HNE) with the concomitant formation of protein adducts. NEP was not inactivated
      to a significant extent by HNE, but some HNE-adduct formation did occur. Prior
      reaction with hydrogen peroxide or AAPH led to enhanced formation of HNE adducts.
      Treatment of IDE with AAHP or hydrogen peroxide increased its susceptibility to
      proteolysis, while treatment of NEP with iron/ascorbate or hydrogen peroxide
      increased its susceptibility to proteolysis. Since IDE and NEP play a prominent
      role in the clearance of amyloid beta peptides, their oxidative inactivation and
      enhanced proteolysis can contribute to the onset and/or progression of
      Alzheimer's disease.

PMID- 16285739
TI  - SR-rich motif plays a pivotal role in recombinant SARS coronavirus nucleocapsid
      protein multimerization.
AB  - The nucleocapsid (N) protein of SARS coronavirus (SARS-CoV) is reported to
      function in encapsidating the viral genomic RNA into helical nucleocapsid, and
      its self-association is believed to be vital in coating the viral genomic RNA.
      Characterization of SARS-CoV N multimerization may thereby help us better
      understand the coronavirus assembly. In the current work, using the yeast two
      hybrid technique, an unexpected interaction between residues 1-210 and 211-290
      (central region) of the SARS-CoV N protein was detected, and SPR results further
      revealed that the SR-rich motif (amino acids 183-197) of SARS-CoV N protein is
      responsible for such an interaction. Chemical cross-linking and gel-filtration
      analyses indicated that the residues 283-422 of the SARS-CoV N protein have
      multimeric ability, although the full-length N protein is prone to exist
      predominantly as dimers. In addition, the multimeric ability of the C-terminal
      domain of SARS-CoV N protein could be weakened by the SR-rich motif interaction
      with the central region (amino acids 211-290). All of these data suggested that
      the SR-rich motif of the SARS-CoV N protein might play an import role in the
      transformation of the SARS-CoV N protein between the dimer and multimer during
      its binding to its central region for self-association or dissociation. This
      current paper will hopefully provide some new ideas in studying SARS-CoV N
      multimerization.

PMID- 16285740
TI  - Oxygen blocks the reaction of the FixL-FixJ complex with ATP but does not
      influence binding of FixJ or ATP to FixL.
AB  - The RmFixL-RmFixJ oxygen signal transduction system ensures that a cascade of the
      Sinorhizobium meliloti nitrogen fixation genes is induced as the concentration of
      O2 drops below 50 microM in symbiotic nodules. Deoxy-RmFixL is a histidine
      protein kinase that catalyzes a phosphoryl transfer from ATP to the aspartate 54
      residue of RmFixJ; RmFixJ is a response regulator that becomes activated as a
      transcription factor by phosphorylation. Association of O2 with a heme-binding
      domain in RmFixL triggers a conformational change that inhibits its kinase
      activity. Here we consider whether this inhibition is achieved by disrupting
      binding of either of the substrates, i.e., RmFixJ or ATP, to the RmFixL kinase.
      The ATP affinities of the oxy and deoxy states were compared via competition of
      ATP against TNP-nucleotide fluorophores. The influence of O2 on formation of the
      RmFixL-RmFixJ complex was investigated by fluorescence polarization. Oxygen
      dramatically inhibited the reaction of the RmFixL-RmFixJ complex with ATP but
      affected neither ATP binding (Kd approximately 100 microM) nor RmFixL-RmFixJ
      complex formation (Kd approximately 4 microM), indicating that inhibition of the
      kinase by the oxy-heme in RmFixL is achieved by inactivating the catalytic site,
      rather than by blocking the association of this enzyme with either of its
      substrates. An 8-fold enhancement of the rate of reaction of RmFixL with ATP in a
      deoxy-RmFixL-D54N RmFixJ complex, compared to that in isolated deoxy-RmFixL,
      exposes the strength of the allosteric effect of RmFixJ on the reaction. These
      results clarify the mechanistic roles of the signal and regulatory partner in
      this signal transduction system.

PMID- 16285741
TI  - The active form of the Saccharomyces cerevisiae ribonucleotide reductase small
      subunit is a heterodimer in vitro and in vivo.
AB  - The class I ribonucleotide reductases (RNRs) are composed of two homodimeric
      subunits: R1 and R2. R2 houses a diferric-tyrosyl radical (Y*) cofactor.
      Saccharomyces cerevisiae has two R2s: Y2 (beta2) and Y4 (beta'2). Y4 is an
      unusual R2 because three residues required for iron binding have been mutated.
      While the heterodimer (betabeta') is thought to be the active form, several
      rnr4delta strains are viable. To resolve this paradox, N-terminally epitope
      tagged beta and beta' were expressed in E. coli or integrated into the yeast
      genome. In vitro exchange studies reveal that when apo-(His6)-beta2 ((His)beta2)
      is mixed with beta'2, apo-(His)betabeta' forms quantitatively within 2 min. In
      contrast, holo-betabeta' fails to exchange with apo-(His)beta2 to form holo
      (His)betabeta and beta'2. Isolation of genomically encoded tagged beta or beta'
      from yeast extracts gave a 1:1 complex of beta and beta', suggesting that
      betabeta' is the active form. The catalytic activity, protein concentrations, and
      Y* content of the rnr4delta and wild type (wt) strains were compared to clarify
      the role of beta' in vivo. The Y* content of rnr4delta is 15-fold less than that
      of wt, consistent with the observed low activity of rnr4delta extracts (<0.01
      nmol min(-1) mg(-1)) versus wt (0.06 +/- 0.01 nmol min(-1) mg(-1)). (FLAG)beta2
      isolated from the rnr4delta strain has a specific activity of 2 nmol min(-1) mg(
      1), similar to that of reconstituted apo-(His)beta2 (10 nmol min(-1) mg(-1)), but
      significantly less than holo-(His)betabeta' (approximately 2000 nmol min(-1) mg(
      1)). These studies together demonstrate that beta' plays a crucial role in
      cluster assembly in vitro and in vivo and that the active form of the yeast R2 is
      betabeta'.

PMID- 16285742
TI  - DNA methylation impacts the cleavage activity of Chlorella virus topoisomerase
      II.
AB  - Topoisomerase II from Paramecium bursaria chlorella virus-1 (PBCV-1) and
      chlorella virus Marburg-1 (CVM-1) displays an extraordinarily high in vitro DNA
      cleavage activity that is 30-50 times higher than that of human topoisomerase
      IIalpha. This remarkable scission activity may reflect a unique role played by
      the type II enzyme during the viral life cycle that extends beyond the normal
      control of DNA topology. Alternatively, but not mutually exclusively, it may
      reflect an adaptation to some aspect of the viral environment that differs from
      the in vitro conditions. To this point, the genomes of many chlorella viruses
      contain high levels of N6-methyladenine (6mA) and 5-methylcytosine (5mC), but the
      DNA employed in vitro is unmodified. Therefore, to determine whether methylation
      impacts the ability of chlorella virus topoisomerase II to cleave DNA, the
      effects of 6mA and 5mC on the PBCV-1 and CVM-1 enzymes were examined. Results
      indicate that 6mA strongly inhibits DNA scission mediated by both enzymes, while
      5mC has relatively little effect. At levels of 6mA and 5mC methylation comparable
      to those found in the CVM-1 genome (10% 6mA and 42% 5mC), the level of DNA
      cleavage decreased approximately 4-fold. As determined using a novel rapid quench
      pre-equilibrium DNA cleavage system in conjunction with oligonucleotide binding
      and ligation assays, this decrease appears to be caused primarily by a slower
      forward rate of DNA scission. These findings suggest that the high DNA cleavage
      activity of chlorella virus topoisomerase II on unmodified nucleic acid
      substrates may reflect, at least in part, an adaptation to act on methylated
      genomic DNA.

PMID- 16285743
TI  - Mechanism for N-acetyl-2-aminofluorene-induced frameshift mutagenesis by
      Escherichia coli DNA polymerase I (Klenow fragment).
AB  - N-Acetyl-2-aminofluorene (AAF) is a chemical carcinogen that reacts with guanines
      at the C8 position in DNA to form a structure that interferes with DNA
      replication. In bacteria, the NarI restriction enzyme recognition sequence
      (G1G2CG3CC) is a very strong mutational hot spot when an AAF adduct is positioned
      at G3 of this sequence, causing predominantly a -2 frameshift GC dinucleotide
      deletion mutation. In this study, templates were constructed that contained an
      AAF adduct at this position, and primers of different lengths were prepared such
      that the primer ended one nucleotide before or opposite or one nucleotide after
      the adduct site. Primer extension and gel shift binding assays were used to study
      the mechanism of bypass by the Escherichia coli DNA polymerase I (Klenow
      fragment) in the presence of these templates. Primer extension in the presence of
      all four dNTPs produced a fully extended product using the unmodified template,
      while with the AAF-modified template synthesis initially stalled at the adduct
      site and subsequent synthesis resulted in a product that contained the GC
      dinucleotide deletion. Extension product and gel shift binding analyses were
      consistent with the formation of a two-nucleotide bulge structure upstream of the
      active site of the polymerase after a nucleotide is incorporated across from the
      adduct. These data support a model in which the AAF adduct in the NarI sequence
      specifically induces a structure upstream of the polymerase active site that
      leads to the GC frameshift mutation and that it is this structure that allows
      synthesis past the adduct to occur.

PMID- 16285744
TI  - Function of domains of human O6-alkylguanine-DNA alkyltransferase.
AB  - O6-Alkylguanine-DNA alkyltransferase (AGT) is an important DNA repair protein
      that protects from alkylating agents by converting O6-alkylguanine to guanine
      forming S-methylcysteine in the AGT protein. The crystal structure of human AGT
      shows clearly the presence of two domains. The N-terminal domain contains a bound
      zinc atom, and zinc binding confers a mechanistic enhancement to repair activity,
      but this domain has no known function. The C-terminal domain contains all
      residues so far implicated in alkyl transfer including the cysteine acceptor site
      (Cys145), the O6-alkylguanine binding pocket, and a DNA binding domain. We have
      expressed and purified the two domains of human AGT separately. The C-terminal
      domain was totally inactive in vitro, but good activity forming S-alkylcysteine
      at Cys145 was obtained after recombination with the N-terminal domain via a
      freeze-thawing procedure. This suggests that the N-terminal domain plays a
      critical structural role in maintaining an active configuration of the C-terminal
      domain. However, this C-terminal domain alone had activity in protecting against
      the cytotoxic and mutagenic activity of the methylating agent, N-methyl-N'-nitro
      N-nitrosoguanidine (MNNG) when expressed in Escherichia coli cells lacking
      endogenous AGT, suggesting that other proteins can fulfill this function.
      Remarkably, the free N-terminal domain of hAGT was able to repair O6-alkylguanine
      in vitro via alkyl transfer provided that zinc ions were present. The N-terminal
      domain was also able to produce moderate protection from MNNG when expressed in
      E. coli. This cryptic Zn2+-dependent DNA repair activity may be relevant to the
      evolution and function of AGTs.

PMID- 16285745
TI  - Biophysical properties of a c-type heme in chemotaxis signal transducer protein
      DcrA.
AB  - Chemotaxis signal transducer protein DcrA from a sulfate-reducing bacterium
      Desulfovibrio vulgaris Hildenborough was previously shown to contain a c-type
      heme in its periplasmic domain (DcrA-N) for sensing redox and/or oxygen [Fu et
      al. (1994) J. Bacteriol. 176, 344-350], which is the first example of a heme
      based sensor protein containing a c-type heme as a prosthetic group. Optical
      absorption and resonance Raman spectroscopies indicates that heme c in DcrA-N
      shows a redox-dependent ligand exchange. Upon reduction, a water molecule that
      may be the sixth ligand of the ferric heme c is replaced by an endogenous amino
      acid. Although the reduced heme in DcrA-N is six-coordinated with two endogenous
      axial ligands, CO can easily bind to the reduced heme to form CO-bound DcrA-N.
      Reaction of the reduced DcrA-N with molecular oxygen results in autoxidation to
      form a ferric state without forming any stable oxygen-bound form probably due to
      the extremely low redox potential of DcrA-N (-250 mV). Our study supports the
      initial idea by Fu et al. that DcrA would act as a redox and/or oxygen sensor, in
      which the ligand exchange between water and an endogenous amino acid is a trigger
      for signal transduction. While the affinity of CO to DcrA-N (Kd = 138 microM) is
      significantly weak compared to those of other heme proteins, we suggest that CO
      might be another physiological effector molecule.

PMID- 16285749
TI  - Potential-directed assembly of aryl iodonium salts onto silicon {100} hydride
      terminated and platinum surfaces.
AB  - A novel electrograft method of forming covalent bonds directly to silicon hydride
      or platinum surfaces has been demonstrated with the use of iodonium salt
      precursors. Initially, a silicon substrate is treated with a dilute hydrofluoric
      acid wash to ensure a hydride-passivated surface, which is immersed in a solution
      of iodonium salt dissolved in a solution of tetrabutylammonium tetrafluoroborate
      in acetonitrile. Grafting is accomplished by applying a negative bias to the
      silicon substrate. Directed assembly has been demonstrated with Pt substrates.

PMID- 16285746
TI  - Self-malonylation is an intrinsic property of a chemically synthesized type II
      polyketide synthase acyl carrier protein.
AB  - During polyketide biosynthesis, malonyl groups are transferred to the acyl
      carrier protein (ACP) component of the polyketide synthase (PKS), and it has been
      shown that a number of type II polyketide ACPs undergo rapid self-acylation from
      malonyl-CoA in the absence of a malonyl-CoA:holo-acyl carrier protein
      transacylase (MCAT). More recently, however, the observation of self-malonylation
      has been ascribed to contamination with Escherichia coli MCAT (FabD) rather than
      an intrinsic property of the ACP. The wild-type apo-ACP from the actinorhodin
      (act) PKS of Streptomyces coelicolor (synthetic apo-ACP) has therefore been
      synthesized using solid-state peptide methods and refolded using the GroEL/ES
      chaperone system from E. coli. Correct folding of the act ACP has been confirmed
      by circular dichroism (CD) and 1H NMR. Synthetic apo-ACP was
      phosphopantetheinylated to 100% by S. coelicolor holo-acyl carrier protein
      synthase (ACPS), and the resultant holo-ACP underwent self-malonylation in the
      presence of malonyl-CoA. No malonylation of negative controls was observed,
      confirming that the use of ACPS and GroEL/ES did not introduce contamination with
      E. coli MCAT. This result proves unequivocally that self-malonylation is an
      inherent activity of this PKS ACP in vitro.

PMID- 16285750
TI  - Locally enhanced relative humidity for scanning probe nanolithography.
AB  - The formation of a water meniscus between a sharp tip and a solid surface is one
      of the prevailing requirements for scanning probe microscope (SPM)-based
      lithographies, such as dip-pen nanolithography (DPN) and conductive tip induced
      oxidation. The water meniscus functions as a medium for the oxidation of or mass
      transfer to the solid surface. Here we report a simple, efficient, and effective
      approach to enhance the local relative humidity and thus increase the size of the
      water meniscus by bringing a water-containing capillary tube to the proximity of
      the tip-surface contact area. The enhancement in local relative humidity is
      confirmed via an increase in the measured tip-surface adhesion forces and the
      widths of DPN generated parallel lines. Compared to the global control of
      relative humidity for the whole lithography system, the short distance between
      the "water reservoir" and the tip-surface contact area enables rapid increase in
      the local vapor pressure of water, less perturbation, and minimal erosion to the
      state-of-the-art electronics. As a result, most scanning probe lithography
      experiments at high relative humidity can now be performed in a reasonable time
      frame.

PMID- 16285751
TI  - Surface grafted antibodies: controlled architecture permits enhanced antigen
      detection.
AB  - The attachment of antibodies to substrate surfaces is useful for achieving
      specific detection of antigens and toxins associated with clinical and field
      diagnostics. Here, acrylated whole antibodies were produced through conjugation
      chemistry, with the goal of covalently photografting these proteins from surfaces
      in a controlled fashion, to facilitate rapid and sensitive antigenic detection. A
      living radical photopolymerization chemistry was used to graft the acrylated
      whole antibodies on polymer surfaces at controlled densities and spatial
      locations by controlling the exposure time and area, respectively. Copolymer
      grafts containing these antibodies were synthesized to demonstrate two
      principles. First, PEG functionalities were introduced to prevent nonspecific
      protein interactions and improve the reaction kinetics by increasing solvation
      and mobility of the antibody-containing chains. Both of these properties lead to
      sensitive (pM) and rapid (<20 min) detection of antigens with this surface
      modification technique. Second, graft composition was tailored to include
      multiple antibodies on the same grafted chains, establishing a means for
      simultaneously detecting multiple antigens on one grafted surface area. Finally,
      the addition of PEG spacers between the acrylate functionality and the pendant
      detection antibodies was tuned to enhance the detection of a short-half-life
      molecule, glucagon, in a complex biological environment, plasma.

PMID- 16285753
TI  - Precipitative growth templated by a fluid jet.
AB  - Tubular growth by chemical precipitation at the interface between two fluids, a
      jet and its surroundings, underlies the development of such important structures
      as chimneys at hydrothermal vents. This growth is associated with strong thermal
      and/or solute gradients localized at those interfaces, and these gradients, in
      turn, often produce radial compositional stratification of the resulting tube
      wall. A fundamental question underlying these processes is how the interplay
      between diffusion, advection, and precipitation determines the elongation rate of
      the tubes. Here we report experimental and theoretical results that reveal a
      regime in which there exists a new scaling law for tube growth. The model system
      studied consists of a jet of aqueous ammonia injected into a ferrous sulfate
      solution, precipitating iron hydroxides with varying oxidation states at the jet
      boundary. Despite the complex chemistry and dynamics underlying the
      precipitation, the tube growth exhibits a strikingly simple scaling form, with
      characteristic lengths and times increasing linearly with the mean velocity of
      the jet. These observations follow from a kinetic model of advection-dominated
      flows.

PMID- 16285752
TI  - Harnessing light to create defect-free, hierarchically structured polymeric
      materials.
AB  - Computer simulations reveal how photoinduced chemical reactions in polymeric
      mixtures can be exploited to create long-range order in materials with features
      that range from the submicron to the nanoscale. The process is initiated by
      shining a spatially uniform light on a photosensitive AB binary blend, which
      thereby undergoes both a reversible chemical reaction and a phase separation.
      When a well-collimated, higher intensity light is rastered over the sample, the
      system forms defect-free, spatially periodic structures. If a nonreactive
      homopolymer C is added to the system, this component localizes in regions that
      are irradiated with a higher intensity light, and one can effectively "write" a
      pattern of C onto the AB film. Rastering over the ternary blend with the
      collimated light now leads to hierarchically ordered patterns of A, B, and C.
      Because our approach involves homopolymers, it significantly expands the range of
      materials that can be fashioned into a periodic pattern. The findings point to a
      facile process for manufacturing high-quality polymeric components in an
      efficient manner.

PMID- 16285754
TI  - Anomalous phase behavior in Langmuir monolayers of monomyristoyl-rac-glycerol at
      the air-water interface.
AB  - The effect of temperature on the surface phase behavior in Langmuir monolayers of
      monomyristoyl-rac-glycerol (MMG) at the air-water interface has been studied by
      film balance and Brewster angle microscopy (BAM). It is observed that the domains
      of the MMG monolayers formed in the coexistence region between the liquid
      expanded (LE) and liquid condensed (LC) phases retain their circular shape over
      the studied temperature range, showing a sharp contrast to the temperature
      dependent monolayer morphologies of amphiphilic systems where the shape of
      condensed domains changes either from compact circular to fingering or from
      irregular or spiral to compact patterns with increasing temperature. It is
      concluded that the system is capable of tuning the line tension of the interface
      by the effect of the increase in the hydrophobic character because of dehydration
      of the headgroup, which imparts to the molecules the properties of similar
      molecules but with less hydrophilic headgroups. As a result, the domains can
      retain their circular shape even up to the maximum possible temperature of the
      phase transition.

PMID- 16285755
TI  - Effects of surfactant and temperature on rheological and structural properties of
      semidilute aqueous solutions of unmodified and hydrophobically modified alginate.
AB  - The dynamic and structural perturbations that result from the interactions
      between the anionic surfactant sodium dodecyl sulfate (SDS) and the
      hydrophobically modified biopolymer alginate (HM-alginate) have been studied with
      the aid of rheological methods, turbidimetry, and small-angle neutron scattering
      (SANS). The rheological results for a semidilute HM-alginate solution in the
      presence of SDS disclose strong interactions between HM-alginate and SDS at a low
      level of surfactant addition, and this feature is accompanied by enhanced
      turbidity. At higher surfactant concentrations the association complexes are
      disrupted. A strong temperature effect of the viscosity is observed in HM
      alginate solutions at moderate SDS concentrations, where an elevated temperature
      leads to enhanced chain mobility, which promotes a breakup of the association
      complexes. The SANS results reveal a pronounced peak in the plot of scattered
      intensity versus wavevector q at intermediate q values for SDS concentrations
      above the critical micelle concentration (cmc). With contrast-matching
      conditions, using deuterated SDS instead of SDS, no interaction peak appears but
      an "upturn" in the scattered intensity is observed at small q value. The
      magnitude of this effect decreases with increasing surfactant concentration,
      showing clearly that SDS is capable of breaking up the large aggregates created.

PMID- 16285756
TI  - Deaggregation behavior of the phenol gemini derivatives.
AB  - The phenol gemini compounds were synthesized by rebuilding the substituents and
      lateral chain on the phenyl ring. Two parts of the molecules were connected by a
      spacer of hydrocarbon chain via ester groups. The deaggregation behaviors of
      target molecules were investigated by studying coaggregation behaviors,
      evaluating the deaggregating abilities in terms of fluorescence measurements, the
      measurements of their aggregation number and the effects on restraining the cell
      adhesion. In present cases, all of these experiments give the same results; that
      is, in these molecules, the longer branched methyl hydrocarbon chain and the
      combination of methoxy with hydroxyl groups on the phenyl ring possess the higher
      deaggregating abilities in the studied situation. The molecules with two
      hydrocarbon chains, i.e., the phenol gemini compounds, are more effective to
      deaggregate the aggregated probes than the molecules with one hydrocarbon chain.
      To find an effective deaggregator might be helpful to design the medicine for the
      cure of arteriosclerosis.

PMID- 16285757
TI  - Movement of colloidal particles in two-dimensional electric fields.
AB  - We characterize the movement of carbon black particles in inhomogeneous, two
      dimensional dc electric fields. Motivated by display applications, the particles
      are suspended in a nonpolar solvent doped with a charge control agent. The two
      dimensional fields are generated between strip electrodes on a glass slide spaced
      120 microm apart with field strengths up to 10(4) V/m. Such fields are
      insufficient to drive either electrohydrodynamic instabilities or natural
      convection due to ohmic heating, but they move the particles between the
      electrodes in about 30 s. In the center region between the strip electrodes, the
      particles move by electrophoresis; that is, the particle velocity is proportional
      to the electric field. However, when imposing a constant-potential or constant
      current boundary condition at the electrodes to derive the electrical field, the
      electrophoretic mobility calculated from the measured particle velocities is
      outside the range of mobilities predicted from the theory of O'Brien and White.
      Near the electrodes the particles either speed up or slow down, depending on the
      polarity of the electrode, and these changes in velocity cannot be explained
      simply by electrophoresis in a spatially varying electric field. We suggest that
      this anomalous motion arises from electrohydrodynamic flows originating from the
      interaction between the space charge of the polarized layers above the electrodes
      and the electric field. Approximate calculations indicate such flows could be
      sufficiently strong to explain the anomalous trajectories near the edges of the
      electrodes.

PMID- 16285758
TI  - Nanostructure and irreversible colloidal behavior of Ca(OH)2: implications in
      cultural heritage conservation.
AB  - Although Ca(OH)2 is one of the oldest art and building material used by mankind,
      little is known about its nanostructural and colloidal characteristics that play
      a crucial role in its ultimate performance as a binder in lime mortars and
      plasters. In particular, it is unknown why hydrated lime putty behaves as an
      irreversible colloid once dried. Such effect dramatically affects the reactivity
      and rheology of hydrated lime dispersions. Here we show that the irreversible
      colloidal behavior of Ca(OH)2 dispersions is the result of an oriented
      aggregation mechanism triggered by drying. Kinetic stability and particle size
      distribution analysis of oven-dried slaked lime or commercial dry hydrate
      dispersions exhibit a significant increase in settling speed and particle
      (cluster) size in comparison to slaked lime putty that has never been dried.
      Drying-related particle aggregation also leads to a significant reduction in
      surface area. Electron microscopy analyses show porous, randomly oriented, micron
      sized clusters that are dominant in the dispersions both before and after drying.
      However, oriented aggregation of the primary Ca(OH)2 nanocrystals (approximately
      60 nm in size) is also observed. Oriented aggregation occurs both before and
      during drying, and although limited before drying, it is extensive during drying.
      Nanocrystals self-assemble in a crystallographically oriented manner either along
      the 100 or equivalent 110 directions, or along the Ca(OH)2 basal planes, i.e.,
      along [001]. While random aggregation appears to be reversible, oriented
      aggregation is not. The strong coherent bonding among oriented nanoparticles
      prevents disaggregation upon redispersion in water. The observed irreversible
      colloidal behavior associated with drying of Ca(OH)2 dispersions has important
      implications in heritage conservation, particularly considering that nowadays
      hydrated lime is often the preferred alternative to portland cement in
      architectural heritage conservation. Finally, our study demonstrates that,
      fortuitously, hydrated lime could be one of the first nanomaterials used by
      mankind.

PMID- 16285759
TI  - Self-aggregation of alkyltrimethylammonium bromides (C10-, C12-, C14-, and
      C16TAB) and their binary mixtures in aqueous medium: a critical and comprehensive
      assessment of interfacial behavior and bulk properties with reference to two
      types of micelle formation.
AB  - The detailed interfacial adsorption and micellization behavior of pure and mixed
      alkyltrimethylammonium bromides (ATABs: C10-, C12-, C14-, and C16TAB) were
      studied using tensiometric, conductometric, fluorimetric, viscometric, and
      calorimetric methods. The critical micellar concentration (CMC), thermodynamics
      of adsorption and micellization, counterion binding, aggregation number, and
      micellar polarity were determined. It was observed that the studied 1:1 molar
      mixtures of C10-C12TAB, C10-C14TAB, and C10-C16TAB, and the mixtures C12-C14TAB
      and C12-C16TAB at different mole ratios produced two CMCs that were supported by
      the conductometric, calorimetric and viscometric methods. Compared to the first
      micelle, the second micelle condensed more counterions and produced a higher
      aggregation number, but their interior polarity states were the same. The surface
      excess, area minimum of the ATABs at the CMC and Gibbs free energy of adsorption
      were evaluated and compared. The ideality/nonideality states of the mixed
      micelles formed in solution were tested in the light of Clint and Rubingh's
      formalisms; the mixed systems were found to undergo moderate to weak synergistic
      interaction. The contributions of the terminal methyl group, the intermediate
      methylene groups, and the hydrophilic tetramethylammonium group toward the
      standard Gibbs free energy, enthalpy, and entropy of the micellization processes
      were deciphered and discussed.

PMID- 16285760
TI  - On the effect of Ca2+ and La3+ on the colloidal stability of liposomes.
AB  - This work deals with the effect of Ca2+ and La3+ on the colloidal stability of
      phosphatidylcholine (PC) liposomes in aqueous media. As physical techniques,
      nephelometry, photon correlation spectroscopy, electrophoretic mobility, and
      surface tension 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 polydispersity values were observed as
      La3+ concentration increases, suggesting that this cation induces the aggregation
      of liposomes. However, changes in polydispersity were not observed with Ca2+,
      suggesting a coalescence mechanism or fusion of liposomes. The stability factor
      (W), calculated from the nephelometry measurements indicated that
      aggregation/fusion occurs at a critical concentration (c.c.) of 0.3 and 0.7 M for
      La3+ and Ca2+, respectively. To gain a better insight into the interaction
      mechanism between the liposomes and the studied ions, the interaction between PC
      monolayers and Ca2+ and La3+ was studied. Changes in the surface area per lipid
      molecule (A0) in the monolayer at the c.c. values were found for both ions, with
      a more pronounced effect in the case of Ca2+. This corresponds with a larger
      reduction of the steric repulsive interaction between the headgroups at the
      phospholipid membrane (pi(head)). The experimental result validates the
      hypothesis made on the liposome fusion in the presence of Ca2+ and liposome
      aggregation in the presence of La3+. These aggregation mechanisms have also been
      confirmed by transmission electron microscopy.

PMID- 16285761
TI  - Crystallization kinetics of colloidal spheres under stationary shear flow.
AB  - A systematic experimental study of dispersions of charged colloidal spheres is
      presented on the effect of steady shear flow on nucleation and crystal growth
      rates. In addition, the nonequilibrium phase diagram as it relates to the melting
      line is measured. Shear flow is found to strongly affect induction times, crystal
      growth rates, and the location of the melting line. The main findings are that
      (1) the crystal growth rate for a given concentration exhibits a maximum as a
      function of the shear rate; (2) contrary to the monotonic increase in the growth
      rate with increasing concentration in the absence of flow, a maximum of the
      crystal growth rate as a function of concentration is observed for sheared
      systems; and (3) the induction time for a given concentration exhibits a maximum
      as a function of the shear rate. These findings are partly explained on a
      qualitative level.

PMID- 16285762
TI  - Kinetics and mechanism of the reaction between ascorbic acid derivatives and an
      arenediazonium salt: cationic micellar effects.
AB  - The effects of tetradecyltrimethylammonium bromide, TTAB, and hexadecyl
      trimethylammonium bromide, CTAB, micellar systems on the reaction of 3
      methylbenzenediazonium, 3MBD, tetrafluoroborate with ascorbic acid, VC, and with
      the hydrophobic derivatives 6-O-dodecyl-L-ascorbic acid, VC12, and 6-O-palmitoyl
      L-ascorbic acid, VC16, were investigated at different pH values by employing a
      combination of UV-vis spectroscopy and high-performance liquid chromatography,
      HPLC, techniques. Previous studies in the absence of surfactant showed that the
      reaction between 3MBD and VC derivatives takes place through a rate-limiting
      decomposition of a transient diazo ether, DE, formed from reaction between 3MBD
      and the monoanion form of ascorbic acid, VC-, in a rapid preequilibrium step. In
      the presence of a fixed [CTAB], the kinetics of the reaction of 3MBD with VC
      follows a saturation kinetics similar to that observed in its absence, but for
      the reaction with VC12 and VC16, only the first linear portions of the saturation
      profiles could be obtained because k(obs) values become too large. HPLC analyses
      of the reaction mixtures show that no unexpected products are detected,
      suggesting that cationic micelles do not modify the mechanism of the reaction.
      Analyses of the kinetic data allowed estimations of the rate constant for the
      decomposition of the diazo ether and of the equilibrium constant for the
      formation of DE in the presence of CTAB micelles, which is approximately 6 times
      higher than in its absence; this suggests that CTAB micelles promote diazo ether
      formation. At constant [antioxidant], the variations of k(obs) for the reactions
      with VC, VC12, or VC16 follow bell-shaped curves, with rate enhancements of up to
      2-3-fold for VC with respect to the value in the absence of surfactant. The rate
      maximum for the reaction of 3MBD with VC is reached at [CTAB] = 0.02 M suggesting
      a CTAB-induced rate increase, i.e., micellar catalysis; meanwhile the rate
      maximum for the reaction with VC12 and VC16, which may behave as amphiphilic
      compounds, is reached at [CTAB] approximately 1 x 10(-4) M, a concentration about
      10 times lower than its critical micelle concentration, cmc, in pure water, but
      only approximately 3 times lower than the cmc of VC16, suggesting the formation
      of reactive CTAB-VC12 and CTAB-VC16 premicellar aggregates. Kinetic and HPLC
      results are consistent with the predictions of the pseudophase model and are
      interpreted in terms of 3MBD ions sampling in the aqueous bulk phase and the
      micellar effects on the different equilibrium involved. The results should
      contribute to a better understanding of the role of compartmentalized systems on
      the efficiency with which hydrophilic and hydrophobic reductants such as ascorbic
      acid derivatives interact with potentially mutagenic and carcinogenic ArN2+ ions.

PMID- 16285763
TI  - Capillary forces between two spheres with a fixed volume liquid bridge: theory
      and experiment.
AB  - Capillary forces are commonly encountered in nature because of the spontaneous
      condensation of liquid from surrounding vapor, leading to the formation of a
      liquid bridge. In most cases, the advent of capillary forces by condensation
      leads to undesirable events such as an increase in the strength of granules,
      which leads to flow problems and/or caking of powder samples. The prediction and
      control of the magnitude of capillary forces is necessary for eliminating or
      minimizing these undesirable events. The capillary force as a function of the
      separation distance, for a liquid bridge with a fixed volume in a sphere/plate
      geometry, was calculated using different expressions reported previously. These
      relationships were developed earlier, either on the basis of the total energy of
      two solid surfaces interacting through the liquid and the ambient vapor or by
      direct calculation of the force as a result of the differential gas pressure
      across the liquid bridge. It is shown that the results obtained using these
      methodologies (total energy or differential pressure) agree, confirming that a
      total-energy-based approach is applicable, despite the thermodynamic
      nonequilibrium conditions of a fixed volume bridge rupture process. On the basis
      of the formulas for the capillary force between a sphere and a plane surface,
      equations for the calculation of the capillary force between two spheres are
      derived in this study. Experimental measurements using an atomic force microscope
      (AFM) validate the formulas developed. The most common approach for transforming
      interaction force or energy from that of sphere/plate geometry to that of
      sphere/sphere geometry is the Derjaguin approximation. However, a comparison of
      the theoretical formulas derived in this study for the interaction of two spheres
      with those for sphere/plate geometry shows that the Derjaguin approximation is
      only valid at zero separation distance. This study attempts to explain the
      inapplicability of the Derjaguin approximation at larger separation distances. In
      particular, the area of a liquid bridge changes with the separation distance, H,
      and thereby does not permit the application of the "integral method," as used in
      the Derjaguin approximation.

PMID- 16285764
TI  - Viscosity increase with temperature in cationic surfactant solutions due to the
      growth of wormlike micelles.
AB  - Wormlike micellar solutions based on ionic surfactants typically show an
      exponential decrease in viscosity upon heating. Here, we report the unusual
      observation of an increasing viscosity with temperature in certain cationic
      wormlike micellar solutions. The solutions contain a cationic surfactant with an
      erucyl (C22, mono-unsaturated) tail and an organic salt, sodium
      hydroxynaphthalene carboxylate (SHNC). When these solutions are heated, their
      zero-shear viscosity increases over a range of temperatures. In some cases, the
      viscosity reaches a peak at a certain temperature and then decreases with further
      heating. The magnitude of the viscosity increase, the onset of this increase, and
      the peak temperature can all be tuned by varying the SHNC concentration. Small
      angle neutron scattering is used to study the origin of this unusual rheological
      behavior. The data reveal that the contour length of the micelles increases with
      temperature, in tandem with the rise in viscosity. A possible explanation for the
      contour length increase, based on a temperature-dependent counterion binding, is
      discussed.

PMID- 16285765
TI  - Aqueous suspensions of charged spherical colloids: dependence of the surface
      charge on ionic strength, acidity, and colloid concentration.
AB  - We theoretically investigate the dependence of the surface charge developed on
      charged spherical colloids upon several environmental parameters: the ionic
      strength of the monovalent added electrolyte, acidity (stabilized by a pH buffer
      solution), and colloid concentration. In the framework of the mean-field Poisson
      Boltzmann spherical cell model, we include the charged colloid-microion
      correlations into the buffer equation, and we allow for the specific binding of
      ions to the ionizable groups on the colloid surface. Theoretical predictions are
      compared to the results obtained under the planar-symmetry Gouy-Chapman
      approximation and analyzed for the experimental conditions of an aqueous
      dispersion of the phospholipid dimyristoyl phosphatidylglycerol (DMPG).
      Experimental measurements of the partition ratio of an aqueous soluble cationic
      spin label on buffered dispersions of polyanionic unilamellar vesicles of DMPG in
      the presence of added monovalent salt are theoretically interpreted in terms of
      ion partition due to electrostatic interactions. We show that the specific
      binding of the probe must be admitted to explain the experimental results.

PMID- 16285766
TI  - Multi length scale analysis of the microstructure in sticky sphere dispersions
      during shear flow.
AB  - The effect of shear flow on the microstructure in a weakly aggregated suspension
      is investigated. Monodisperse small silica particles with a grafted layer of 1
      octadecanol are dispersed in n-tetradecane, yielding a thermoreversible sticky
      sphere model suspension. A combination of small angle light scattering and ultra
      small and small-angle X-ray scattering techniques have been used, in situ and
      time resolved, to study the flow-induced anisotropy of the microstructure. In
      this manner, the length scales from the single particle size to that of the
      spatial organization of the aggregates can be covered. Harmonic expansion of the
      structure factor demonstrates that anisotropy develops in the microstructure on
      all relevant length scales. Possible real space interpretations of the scattering
      information are discussed in conjunction with implications for the nonlinear
      rheological behavior.

PMID- 16285767
TI  - Synthesis and characterization of biocompatible, thermoresponsive ABC and ABA
      triblock copolymer gelators.
AB  - The synthesis of doubly thermoresponsive PPO-PMPC-PNIPAM triblock copolymer
      gelators by atom transfer radical polymerization using a PPO-based macroinitiator
      is described. Provided that the PPO block is sufficiently long, dynamic light
      scattering and differential scanning calorimetry studies confirm the presence of
      two separate thermal transitions corresponding to micellization and gelation, as
      expected. However, these ABC-type triblock copolymers proved to be rather
      inefficient gelators: free-standing gels at 37 degrees C required a triblock
      copolymer concentration of around 20 wt%. This gelator performance should be
      compared with copolymer concentrations of 6-7 wt% required for the PNIPAM-PMPC
      PNIPAM triblock copolymers reported previously. Clearly, the separation of
      micellar self-assembly from gel network formation does not lead to enhanced
      gelator efficiencies, at least for this particular system. Nevertheless, there
      are some features of interest in the present study. In particular, close
      inspection of the viscosity vs temperature plot obtained for a PPO43-PMPC160
      PNIPAM81 triblock copolymer revealed a local minimum in viscosity. This is
      consistent with intramicelle collapse of the outer PNIPAM blocks prior to the
      development of the intermicelle hydrophobic interactions that are a prerequisite
      for macroscopic gelation.

PMID- 16285768
TI  - Preparation of a highly stable niosome and its hydrotrope-solubilization action
      to drugs.
AB  - Highly stable niosomes are prepared and investigated in
      Tween80/PEG6000/Span80/H2O system. The mean radius of the niosomes is 0.15-0.2
      microm. The contents of PEG6000 and Span80 and the system temperature affect the
      size and the stability of the niosome. A certain Span80 can remarkably improve
      the stability. The niosome is provided distinctly with the hydrotrope
      solubilization action to the hydrophilic drug and hydrophobic drug, which affects
      the niosome membrane. The mechanism of the effects of PEG6000 and Span80 on the
      niosome is discussed in this paper.

PMID- 16285769
TI  - Phase behavior and 3D structure of strongly attractive microsphere-nanoparticle
      mixtures.
AB  - We investigate the phase behavior and 3D structure of strongly attractive
      mixtures of silica microspheres and polystyrene nanoparticles. These binary
      mixtures are electrostatically tuned to promote a repulsion between like-charged
      (microsphere-microsphere and nanoparticle-nanoparticle) species and a strong
      attraction between oppositely charged (microsphere-nanoparticle) species. Using
      confocal fluorescence scanning microscopy, we directly observe the 3D structure
      of colloidal phases assembled from these mixtures as a function of varying
      composition. In the absence of nanoparticle additions, the charged-stabilized
      microspheres assemble into a polycrystalline array upon sedimentation. With
      increasing nanoparticle volume fraction, nanoparticle bridges form between
      microspheres, inducing their flocculation. At even higher nanoparticle volume
      fractions, the microspheres become well coated with nanoparticles, leading to
      their charge reversal and subsequent restabilization. We demonstrate how this
      fluid-gel-fluid transition can be utilized to control the morphology of the
      colloidal phases formed under gravity-driven sedimentation.

PMID- 16285770
TI  - Melamine-barbiturate/cyanurate binary organogels possessing rigid azobenzene
      tether moiety.
AB  - Binary organogels were prepared from coaggregates of azobenzene-tethered melamine
      dimer and cyanurate/barbiturates. In the gels of hydrocarbon liquids, the
      coaggregates formed heavily entangled nanofibers, morphologies of which are
      dramatically different from the previously reported coaggregates based on
      flexible dodecamethylene-tethered melamine dimers. In the present systems, the
      rigidity of the azobenzene tether may induce regular packing of molecules. In
      addition, UV-vis and IR spectroscopic measurements provided unequivocal evidence
      for the contribution of the central amide groups and the azobenzene chromophores
      in the tether moiety upon forming well-defined nanofibers by hydrogen-bonding and
      face-to-face (H-type) pi-pi stacking interactions, respectively. As a result of
      tight molecular packing in the self-assembled nanofibers, the azobenzene moiety
      in the gel state showed remarkable resistance to trans --> cis isomerization upon
      irradiation with UV light.

PMID- 16285771
TI  - Analysis of droplet evaporation on a superhydrophobic surface.
AB  - The evaporation process for small, 1-2-mm-diameter droplets of water from
      patterned polymer surfaces is followed and characterized. The surfaces consist of
      circular pillars (5-15 microm diameter) of SU-8 photoresist arranged in square
      lattice patterns such that the center-to-center separation between pillars is 20
      30 microm. These types of surface provide superhydrophobic systems with
      theoretical initial Cassie-Baxter contact angles for water droplets of up to 140
      167 degrees, which are significantly larger than can be achieved by smooth
      hydrophobic surfaces. Experiments show that on these SU-8 textured surfaces water
      droplets initially evaporate in a pinned contact line mode, before the contact
      line recedes in a stepwise fashion jumping from pillar to pillar. Provided the
      droplets of water are deposited without too much pressure from the needle, the
      initial state appears to correspond to a Cassie-Baxter one with the droplet
      sitting upon the tops of the pillars. In some cases, but not all, a collapse of
      the droplet into the pillar structure occurs abruptly. For these collapsed
      droplets, further evaporation occurs with a completely pinned contact area
      consistent with a Wenzel-type state. It is shown that a simple quantitative
      analysis based on the diffusion of water vapor into the surrounding atmosphere
      can be performed, and estimates of the product of the diffusion coefficient and
      the concentration difference (saturation minus ambient) are obtained.

PMID- 16285772
TI  - Self-assembly, characterization, and chemical stability of isocyanide-bound
      molecular wire monolayers on gold and palladium surfaces.
AB  - Self-assembled monolayers (SAMs) of the isocyano derivative of 4,4'-di(phenylene
      ethynylene)benzene (1), a member of the "OPE" family of "molecular wires" of
      current interest in molecular electronics, have been prepared on smooth, {111}
      textured films of Au and Pd. For assembly in oxygen-free environments with
      freshly deposited metal surfaces, infrared reflection spectroscopy (IRS)
      indicates the molecules assume a tilted structure with average tilt angles of 18
      24 degrees from the surface normal. The combination of IRS, X-ray photoelectron
      spectroscopy, and density functional theory calculations all support a single
      sigma-type bond of the -NC group to the Au surface and a sigma/pi-type of bond to
      the Pd surface. Both SAMs show significant chemical instability when exposed to
      typical ambient conditions. In the case of the Au SAM, even a few hours storage
      in air results in significant oxidation of the -NC moieties to -NCO (isocyanate)
      with an accompanying decrease in surface chemical bonding, as evidenced by a
      significant increase in instability toward dissolution in solvent. In the case of
      the Pd SAM, similar air exposure does not result in incorporation of oxygen or
      loss of solvent resistance but rather results in a chemically altered interface
      which is attributed to polymerization of the -NC moieties to quasi-2D poly(imine)
      structures. Conductance probe atomic force microscope measurements show the
      conductance of the degraded Pd SAMs can diminish by approximately 2 orders of
      magnitude, an indication that the SAM-Pd electrical contact has severely
      degraded. These results underscore the importance of careful control of the
      assembly procedures for aromatic isocyanide SAMs, particularly for applications
      in molecular electronics where the molecule-electrode junction is critical to the
      operational characteristics of the device.

PMID- 16285773
TI  - Effect of dehydration on sulfate coordination and speciation at the Fe
      (hydr)oxide-water interface: a molecular orbital/density functional theory and
      Fourier transform infrared spectroscopic investigation.
AB  - The effect of dehydration on the coordination and speciation of sulfate at the Fe
      (hydr)oxide-H2O interface was investigated using molecular orbital/density
      functional theory (MO/DFT) and Fourier transform infrared (FTIR) spectroscopy. IR
      frequency calculations were performed at the UB3LYP/6-31+G(d) level of theory for
      potential sulfate (bidentate bridging, monodentate, and H-bonded) and bisulfate
      (bidentate bridging and monodentate) surface complexes. MO/DFT calculated IR
      frequencies were compared to available IR literature results and attenuated total
      reflectance (ATR) FTIR spectra collected in our laboratory of sulfate adsorbed at
      the hematite-H2O interface. IR frequency calculations performed using the larger
      6-311+G(d,p) basis set resulted in minor frequency shifts that did not
      dramatically alter the agreement with experiment. This investigation proposes
      that sulfate undergoes a speciation change as a function of surface dehydration.
      A generalized model for the speciation change is proposed as follows. (1) At the
      Fe-(hydr)oxide-H2O interface, sulfate adsorbs as a bidentate bridging or
      monodentate surface complex under most experimental conditions. (2) Upon surface
      dehydration, sulfate changes speciation to form bidentate bridging and/or
      monodentate bisulfate. However, surface dehydration does not yield 100%
      speciation change but leads to a mixture of sulfate and bisulfate. (3) The
      speciation change is reversible as a function of rehydration. The reversibility
      of the sulfate-bisulfate speciation change is chiefly determined by the local
      hydration environment of the O-H bond in bisulfate. Under dehydrated conditions,
      the O-H bond length is approximately 0.98 A. The bond length substantially
      increases (bond strength decreases) to approximately 1.03 A when the initial H
      bond network is re-established through hydration, likely leading to deprotonation
      upon full mineral surface hydration.

PMID- 16285774
TI  - Novel alignment mechanism of liquid crystal on a hydrogenated amorphous silicon
      oxide.
AB  - The mechanism of liquid crystal (LC) alignment has been investigated during the
      last few decades for inorganic materials as well as for organic materials;
      however, it has not been clearly confirmed for some alignment materials.
      Inorganic alignment materials such as amorphous silicon oxide (a-SiOx) and
      hydrogenated amorphous silicon oxide (a-SiOx:H) are deposited on indium tin oxide
      (ITO) films on glass by reactive sputtering deposition. After deposition, the
      inorganic alignment materials are irradiated using an Ar+ ion beam (IB) for LC
      alignment. On the basis of the experimental results, a-SiOx films deposited by
      the sputtering do not align the LC, but a-SiOx:H films treated with varying IB
      energies, IB incident angles, IB doses, and IB irradiation times have excellent
      alignment properties and electrooptical properties, identical to those of
      polyimide (PI). These results imply that inorganic alignment layers irradiated by
      IB can be adopted as an LC alignment layer instead of rubbed PI. Additionally,
      hydrogen plays an important role in LC alignment because of the difference in
      alignment properties between a-SiOx films and a-SiOx:H films. We investigate the
      mechanism of IB-treated inorganic alignment layers and suggest that LCs are
      aligned by chemical effects, such as van der Waals interaction, more than by
      physical effects, such as morphology effects, in the inorganic alignment layer
      irradiated by IB.

PMID- 16285775
TI  - Honeycomb pattern formation via polystyrene/poly(2-vinylpyridine) phase
      separation.
AB  - The surface morphologies and properties of polystyrene (PS)/poly(2-vinylpyridine)
      (PVP) blend films cast on the mica substrate from ethylbenzene solution were
      investigated upon controlling different weight ratios and solvent evaporation
      rates. A near-honeycomblike surface morphology of the PS/PVP blend film formed
      under controlling the solvent evaporation rate due to the effect of Marangoni
      Benard convection. The results of static water contact angles, X-ray
      photoelectron spectroscopy, solvent selective etching, and treatment by water
      illustrated that the near-honeycomblike structures on the surface of PS/PVP blend
      films were different for different weight ratios of PS and PVP. After treatment
      with water for several minutes, PVP islands-like structure emerged in the holes
      of the film for a PS/PVP weight ratio of 4/1, and a quasihexagonal arrangement of
      alternate big and small PVP droplets emerged on the top layer of the film for a
      PS/PVP weight ratio of 7/1. The formation mechanisms of different surface
      structures and their response behaviors to water were discussed.

PMID- 16285776
TI  - The application of diffuse reflectance infrared spectroscopy and temperature
      programmed desorption to investigate the interaction of methanol on eta-alumina.
AB  - The adsorption of methanol and its subsequent transformation to form dimethyl
      ether (DME) on a commercial grade eta-alumina catalyst has been investigated
      using a combination of mass selective temperature-programmed desorption (TPD) and
      diffuse reflectance infrared spectroscopy (DRIFTS). The infrared spectrum of a
      saturated overlayer of methanol on eta-alumina shows the surface to be comprised
      of associatively adsorbed methanol and chemisorbed methoxy species. TPD shows
      methanol and DME to desorb with respective maxima at 380 and 480 K, with
      desorption detectable for both molecules up to ca. 700 K. At 673 K, infrared
      spectroscopy reveals the formation of a formate species; the spectral line width
      of the antisymmetric C-O stretch indicates the adoption of a high symmetry
      adsorbed state. Conventional TPD using a tubular reactor, combined with mass
      spectrometric analysis of the gas stream exiting the IR cell, indicate hydrogen
      and methane evolution to be associated with formation of the surface formate
      group and CO evolution with its decomposition. A reaction scheme is proposed for
      the generation and decomposition of this important reaction intermediate. The
      overall processes involved in (i) the adsorption/desorption of methanol, (ii) the
      transformation of methanol to DME, and (iii) the formation and decomposition of
      formate species are discussed within the context of a recently developed four
      site model for the Lewis acidity of eta-alumina.

PMID- 16285777
TI  - Immobilization of myoglobin on phosphate and phosphonate grafted-zirconia
      nanoparticles.
AB  - We investigated the adsorption and catalytic activity of myoglobin (Mb)
      immobilized on colloidal particles of zirconia covalently grafted with phosphoric
      (ZrO2-P) and benzenephosphonic acid (ZrO2-BP). The maximum adsorption was reached
      after 1 h of contact and was greater on a hydrophilic support, ZrO2-P, compared
      to a hydrophobic support, ZrO2-BP. The equilibrium isotherms fitted the Langmuir
      equation, suggesting the presence of a monolayer of protein molecules on the
      surface of the nanoparticles. The nanostructured biocomposites are active in the
      oxidation of 2-methoxyphenol (guaiacol) by hydrogen peroxide. The oxidation
      catalyzed by immobilized Mb followed a Michaelis-Menten kinetics, similar to that
      observed in the oxidation by free Mb. Furthermore, the catalytic efficiency is
      similar to that of free Mb and higher than that of "large-size" biocatalysts
      (with sizes larger than 1 mum). In the latter case, the kinetic parameters,
      k(cat) and K(M), indicate that this is mostly due to an increased affinity of the
      nano-biocomposite for the substrate. The activity of the nano-biocomposites
      decreases slightly as the amount of adsorbed protein increases. This is mainly
      due to the formation of a nonordered monolayer, which reduces the accessibility
      of the substrate to the active center.

PMID- 16285778
TI  - Covalent bonding of alkene and alkyne reagents to graphitic carbon surfaces.
AB  - Various aromatic and aliphatic alkynes and one alkene were covalently bonded to
      sp(2)-hybridized carbon surfaces by heat treatment in an argon atmosphere. X-ray
      photoelectron spectroscopy, Raman, and FTIR spectra of the modified surfaces
      showed that the molecules were intact after the 400 degrees C heat treatment but
      that the alkyne group had reacted with the surface to form a covalent bond.
      Alkynes with ferrocene and porphyrin centers exhibited chemically reversible
      voltammetric waves that could be cycled many times. Atomic force microscopy of
      the modified surfaces indicated a thickness of the molecular layer consistent
      with monolayer coverage, and surface coverage determined by voltammetry was also
      in the monolayer range. Raman spectroscopy of the porphyrin monolayers formed
      from a porphyrin alkyne showed no evidence for dimer formation, although
      multilayer formation may occur at undetected levels. FTIR spectra of the
      porphyrin-modified carbon surfaces were well-defined, similar to the parent
      molecule, and indicative of an average tilt angle between the porphyrin plane and
      the surface normal of 37 degrees . The bond between the molecular monolayer and
      the carbon surface was quite stable, withstanding sonication in tetrahydrofuran,
      mild aqueous acid and base, and repeated voltammetric cycling in propylene
      carbonate electrolyte. Heat treatment of alkynes and alkenes appears to be a
      generally useful method for modifying carbon surfaces, which can be applied to
      both aromatic and aliphatic molecules.

PMID- 16285779
TI  - Effects of substrate polarity and chain length on conformational and thermal
      properties of phosphonic acid self-assembled bilayers.
AB  - Conformational and thermal behavior of self-assembled structures of three
      phosphonic acids, OPA (octadecylphosphonic acid), TPA (tetradecylphosphonic
      acid), and OcPA (octylphosphonic acid), with different alkyl chain lengths are
      investigated and compared. The orientation of self-assembled bilayers depends on
      whether the substrate is nonpolar (graphite) or polar (mica). For nonpolar
      substrates, bilayers lay parallel to the surface, and for polar substrates,
      bilayers lay perpendicular to the surface. Thermal behaviors of these structures
      on mica and graphite are also investigated, showing that, depending on the
      temperature they are submitted to, molecules stack, unstack, or agglomerate on
      mica and form larger domains on graphite.

PMID- 16285780
TI  - Covalently networked monolayer-protected nanoparticle films.
AB  - Covalently networked films of nanoparticles can be assembled on various
      substrates from functionalized monolayer-protected clusters (MPCs) via ester
      coupling reactions. Exposure of a specifically modified substrate to alternating
      solutions of 11-mercaptoundecanoic acid exchanged and 11-mercaptoundecanol
      exchanged MPCs, in the presence of ester coupling reagents, 1,3
      dicyclohexylcarbodiimide and 4-(dimethylamino)pyridine, results in the formation
      of a multilayer film with ester bridges between individual nanoparticles. These
      films can be grown in a controlled manner to various thicknesses and exhibit
      certain properties that are consistent with films having other types of
      interparticle connectivity, including chemical vapor response behavior and
      quantized double layer charging. Ester coupling of MPCs into assembled films is a
      straightforward and highly versatile approach that results in robust films that
      can endure harsher chemical environments than other types of films. The stability
      of these covalent films is assessed and compared to other more traditional MPC
      film assemblies.

PMID- 16285781
TI  - Fabrication and photoluminescence of hybrid organized molecular films of a series
      of gemini amphiphiles and europium(III)-containing polyoxometalate.
AB  - Organic/inorganic hybrid monolayers, consisting of an oval decatungstoeuropate
      (EuW10) with photoluminescence and a series of gemini-type amphiphiles with
      various lengths of the flexible hydrophobic spacers, were formed through
      electrostatic interaction at the air/water interface. The ultrathin hybrid
      multilayer films could be fabricated through the horizontal transfer of the
      monolayers onto the solid substrates. The characteristic absorption band of EuW10
      in the UV spectra of the hybrid films showed a slight red shift in comparison
      with that in solution, indicating the ordered arrangement of EuW10 in the hybrid
      films. FT-IR spectra of the hybrid films presented characteristic bands of EuW10,
      indicating that the structure of the cluster was kept in the films. X-ray
      diffraction measurements of the films revealed that the well-defined layer
      structures were formed in these multilayer films and the EuW10 cluster ions were
      orientated with their short axis parallel to the film surface. Typical
      photoluminescence of the 5D0 --> 7F2 and 5D0 --> 7F1 transitions of EuW10 was
      observed in the hybrid films. Interestingly, the relative intensity of the two
      emission bands varied with the spacer length of the gemini amphiphiles in the
      films. A size matching between EuW10 and the gemini amphiphile with a
      hexamethylene spacer was observed, which showed the lowest ratio of the emission
      intensity of 5D0 --> 7F2 to that of 5D0 --> 7F1. Circular nanoparticles were
      observed in the AFM images for all these hybrid films. In addition, the size of
      the formed nanoparticles showed a dependence on the spacer length.

PMID- 16285782
TI  - Synthesis and characterization of tapered copolymer brushes via surface-initiated
      atom transfer radical copolymerization.
AB  - Tapered copolymer brushes of methyl methacrylate (MMA) and 2-hydroxyethyl
      methacrylate (HEMA) were synthesized via surface-initiated atom transfer radical
      polymerization (ATRP) by gradual addition of HEMA to a reaction mixture that
      originally only had MMA as monomer. The copolymer brush grew linearly with
      polymerization time. The tapered copolymer brushes responded to selective solvent
      treatments. For the same tapered copolymer brush, pretreating the surface with
      methylene chloride made the surface more hydrophobic; pretreating the surface
      with methanol increased the surface hydrophilicity. This change in surface
      properties was reversible and considered to be caused by the solvent induced
      rearrangement of the polymer brushes, which is supported by atomic force
      microscopy images of the surface. Our work demonstrates that the properties of
      the tapered copolymer brush could be finely tuned by careful control of the
      composition profile.

PMID- 16285783
TI  - Coupling of carbon monoxide molecules over oxygen-defected UO2(111) single
      crystal and thin film surfaces.
AB  - While coupling reactions of carbon-containing compounds are numerous in
      organometallic chemistry, they are very rare on well-defined solid surfaces. In
      this work we show that the reductive coupling of two molecules of carbon monoxide
      to C2 compounds (acetylene and ethylene) could be achieved on oxygen-defected
      UO2(111) single crystal and thin film surfaces. This result allows in situ
      electron spectroscopic investigation of a typical organometallic reaction such as
      carbon coupling and extends it to heterogeneous catalysis and solids. By using
      high-resolution photoelectron spectroscopy (HRXPS) it was possible to track the
      changes in surface states of the U and O atoms as well as identify the
      intermediate of the reaction. Upon CO adsorption U cations in low oxidation
      states are oxidized to U4+ ions; this was accompanied by an increase of the O-to
      U surface ratios. The HRXPS C 1s lines show the presence of adsorbed species
      assigned to diolate species (-OCH=CHO-) that are most likely the reaction
      intermediate in the coupling of two CO molecules to acetylene and ethylene.

PMID- 16285784
TI  - Rigid sphere molecular model enables an assessment of the pore curvature effect
      upon realistic evaluations of surface areas of mesoporous and microporous
      materials.
AB  - A gas adsorption rigid spheres model (RSM) was incorporated into the CPSM model
      (corrugated pore structure model) to correlate the pore surface areas obtained
      from the BET and CPSM methods. The latter is a method simulating the gas sorption
      hysteresis loop and enables the evaluation of surface areas S(CPSM) through the
      integration of the pertinent pore size distributions. Thus, S(CPSM) values are
      inherently influenced by pore curvature. The new CPSM-RSM version estimates
      surface areas S(CPSMfs) that are independent of pore curvature and can be
      compared with the pertinent S(BET) values. The RSM exploits the fact that a
      curved pore surface accommodates fewer molecules, assumed to behave as rigid
      spheres, than an equal flat one. Thus, the RSM accounts for a higher molecular
      surface coverage Ac (nm2/molec.) in pores with marked curvature than that (i.e.,
      Af) on a flat surface. The ratio Ac/Af for nitrogen adsorbed on single pore sizes
      varies in the range Ac/Af = 1.44-1.03 for pore sizes D = 1.5-15 nm, respectively.
      Also for D = 1.5-5.0 nm the S(CPSMfs) and S(BET) values are lower by
      approximately 10-45% than the S(CPSM) estimates. From the application of the CPSM
      RSM model on several porous materials exhibiting all known types of sorption
      hysteresis loops, it was confirmed that S(BET) approximately S(CPSMfs) (+/-5%)
      and (S(CPSM) - S(BET))/S(BET) = 3-68% for the materials examined. In conclusion,
      the BET method may produce quite conservative surface area estimates for
      materials exhibiting pore structures with appreciable pore curvature, whereas the
      CPSM-RSM model can reliably predict both S(CPSM) and S(CPSMfs) = S(BET) values.

PMID- 16285785
TI  - Observation of zinc phthalocyanine aggregates on a water surface using grazing
      incidence X-ray scattering.
AB  - Reported here are the structural properties of a zinc 2,9,16,23-tetra-tert-butyl
      29H,31H-phthalocyanine Langmuir monolayer on a water surface under progressive
      lateral compression investigated by grazing incidence X-ray scattering. Grazing
      incidence diffuse X-ray scattering out of the specular plane (GIXOS) is exploited
      to determine specular reflectivity-like information where the phase change of
      flat-lying molecules on the surface to edge-standing molecules perpendicular to
      the surface is directly observed. Furthermore, grazing incident X-ray diffraction
      (GIXD) is used to investigate the in-plane ordering of the system where it has
      been found that in the high-density state (approximately 0.35 nm2 per molecule)
      the system can be considered to be a monolayer consisting of arrays of side-by
      side lying cofacially aggregated cylindrical rodlike entities.

PMID- 16285786
TI  - Determining the association constant and adsorption properties of ion pairs in
      water by fitting surface tension data.
AB  - Association constants and adsorption parameters of tetraalkylammoniumdodecyl
      sulfate (TAADS) ion pairs in water were determined. We have analyzed water/air
      surface tension measurements obtained for mixtures of sodium dodecyl sulfate
      (SDS) and tetraalkylammonium bromide of increasing chain lengths (TMAB, TEAB,
      TPAB, and TBAB). To reproduce the experimental isotherms, we coupled the
      association equilibrium of the ion pairs to the equations proposed by Fainerman
      and co-workers to model the adsorption of binary mixtures of surfactants (SDS and
      TAADS) with different molar areas at a nonideal surface layer. The parameters
      found showed that the model is not convenient to describe the effect of the
      addition of TMAB but a clear coherency was obtained for the three longer
      compounds. Ranging from TEADS to TBADS increasing hydrophobic interactions give
      rise to a higher associability but to a lower surface activity. Self-interactions
      coefficients extracted by the fitting procedure confirmed the importance of
      attractive interactions between the ion pairs. The calculated surface coverage
      showed that in every case the compound mainly adsorbed at the interface was the
      ion pair. For TBADS strong attractive interactions result in a phase transition
      at very low concentration.

PMID- 16285787
TI  - Fast removal and recovery of Cr(VI) using surface-modified jacobsite (MnFe2O4)
      nanoparticles.
AB  - In this work, the effectiveness of surface-modified jacobsite (MnFe2O4)
      nanoparticles was investigated for the removal and recovery of Cr(VI) from
      synthetic wastewater. Ten nanometer modified MnFe2O4 nanoparticles were produced
      to be a new adsorbent using a co-precipitation method followed by a surface redox
      reaction. The equilibrium time for Cr(VI) adsorption onto modified MnFe2O4
      nanoparticles was as short as 5 min, and the adsorption data fit the Langmuir
      model well. The maximum uptake of 31.5 mg of Cr(VI)/g of modified MnFe2O4 was
      obtained at pH 2, which was comparable with other common adsorbents such as
      activated carbon and sawdust. The effects of ligands (EDTA, SO4(2-), NH4+) and
      ionic strength were studied in a pH range of 2-10. EDTA and SO4(2-) inhibited the
      adsorption of Cr(VI) over the entire pH range studied, whereas NH4+ enhanced the
      uptake of Cr(VI) at pH greater than 6.5. The mechanisms leading to Cr(VI)
      adsorption by modified MnFe2O4 nanoparticles were determined by X-ray diffraction
      and X-ray photoelectron spectroscopy to be a combination of electrostatic
      interaction and ion exchange. Regeneration studies indicated the potential reuse
      of the modified MnFe2O4 nanoparticles without sacrificing adsorption capacity and
      the possible recycling of Cr(VI) without changing the valence.

PMID- 16285788
TI  - Hydrolytic behavior of enantiomeric poly(lactide) mixed monolayer films at the
      air/water interface: stereocomplexation effects.
AB  - The Langmuir film balance technique was used to determine the hydrolytic kinetics
      of monolayers of the stereocomplex formed from mixtures of enantiomeric
      polylactides, poly(L-lactide) (L-PLA) and poly(D-lactide) (D-PLA), spread at the
      air-water interface. The present study investigated parameters such as
      degradation medium, mixture composition, and time on the relative degradation
      rate. The pi-A isotherms of monolayers of the mixtures provide clear evidence for
      the presence of a stereocomplex; the isotherms of monolayers of individual
      polyenantiomer show a transition at about 8.5 mN/m, whereas the transition of
      monolayers containing a stereocomplex formed from the equimolar mixture shifted
      to higher surface pressure, about 11 mN/ m. The rate of hydrolysis was recorded
      by a change in occupied area when the monolayer is maintained at a constant
      surface pressure. The hydrolysis of the mixture monolayers under basic conditions
      was slower than that of individual polyenantiomer monolayers, depending on the
      composition or the degree of complexation. In the presence of proteinase K, the
      enzymatic hydrolysis rate of mixture monolayers with >50 mol % l-PLA was much
      slower than that of the single-component L-PLA monolayer. The monolayers formed
      from mixtures with < or =50 mol % L-PLA did not show any change of occupied
      areas. This result is explained by the inactivity of D-PLA and stereocomplexed
      chains to the enzyme. From both results, it can be concluded that the retardation
      of the hydrolysis of mixture monolayers is mainly due to a strong interaction
      between D- and L-lactide unit sequences, which prevents the penetration of water
      or enzyme into the bulk.

PMID- 16285789
TI  - Ideal nonideality in adsorption of 2-aminoethanethiol and 2-mercaptoethane
      sulfonic acid to form electrostatically stabilized binary self-assembled
      monolayers on Au(111).
AB  - In formation of binary self-assembled monolayers (SAMs) composed of 2
      aminoethanethiol (AET) and 2-mercaptoethane sulfonic acid (MES) by adsorption
      from an ethanol solution on Au(111), the adsorption shows nearly ideal
      nonideality in that the surface ratio of MES to AET in the SAM is unity and does
      not depend on the mixing ratio of MES to AET in the bathing ethanol solution used
      for preparing SAMs, chi(soln)MES, over the wide range of chi(soln)MES between
      0.01 and 0.95. X-ray photoelectron spectroscopy confirms that at least 80% of AET
      molecules adsorbed are protonated in this range of chi(soln)MES, indicating that
      the electrostatic interaction between positively charged AET and negatively
      charged MES is responsible to the observed nonideality. Correspondingly, there
      appears only one cathodic peak in a linear-sweep voltammogram of the reductive
      desorption of the SAM, having a narrow full width at half-maximum of about 20 mV.
      This suggests the presence of strong lateral attractive interaction between the
      adsorbed thiolates.

PMID- 16285790
TI  - Capillary forces between spherical particles floating at a liquid-liquid
      interface.
AB  - We study the capillary forces acting on sub-millimeter particles (0.02-0.6 mm)
      trapped at a liquid-liquid interface due to gravity-induced interface
      deformations. An analytical procedure is developed to solve the linearized
      capillary (Young-Laplace) equation and calculate the forces for an arbitrary
      number of particles, allowing also for a background curvature of the interface.
      The full solution is expressed in a series of Bessel functions with coefficients
      determined by the contact angle at the particle surface. For sub-millimeter
      spherical particles, it is shown that the forces calculated using the lowest
      order term of the full solution (linear superposition approximation; LSA) are
      accurate to within a few percents. Consequently the many particle capillary force
      is simply the sum of the isolated pair interactions. To test these theoretical
      results, we use video microscopy to follow the motion of individual particles and
      pairs of interacting particles at a liquid-liquid interface with a slight
      macroscopic background curvature. Particle velocities are determined by the
      balance of capillary forces and viscous drag. The measured velocities (and thus
      the capillary forces) are well described by the LSA solution with a single
      fitting parameter.

PMID- 16285791
TI  - Dynamics of imbibition into a pore with a heterogeneous surface.
AB  - We use large-scale molecular dynamics simulations to study the dynamics of liquid
      penetration into a cylindrical pore having a randomly heterogeneous surface
      comprising areas of differing wettability. Our results confirm that the
      equilibrium contact angle in the heterogeneous pore is well described by Cassie's
      law. As in the case of the uniform pore studied previously, the dynamics of
      penetration can be described by the Lucas-Washburn equation corrected to include
      the effect of a dynamic contact angle. The dissipation at the three-phase line,
      which gives rise to the dynamic contact angle, may be characterized in terms of a
      friction coefficient. Interestingly, the wetting-line friction on the
      heterogeneous surface also turns out to be a linear function of the fractional
      concentration of the areas of different wettability, analogous to Cassie's law.
      These results can be interpreted in terms of an independent random walk
      mechanism.

PMID- 16285792
TI  - Superhydrophobicity on two-tier rough surfaces fabricated by controlled growth of
      aligned carbon nanotube arrays coated with fluorocarbon.
AB  - Considerable effort has been expended on theoretical studies of superhydrophobic
      surfaces with two-tier (micro and nano) roughness, but experimental studies are
      few due to the difficulties in fabricating such surfaces in a controllable way.
      The objective of this work is to experimentally study the wetting and
      hydrophobicity of water droplets on two-tier rough surfaces for comparison with
      theoretical analyses. To compare wetting on micropatterned silicon surfaces with
      wetting on nanoscale roughness surfaces, two model systems are fabricated: carbon
      nanotube arrays on silicon wafers and carbon nanotube arrays on carbon nanotube
      films. All surfaces are coated with 20 nm thick fluorocarbon films to obtain low
      surface energies. The results show that the microstructural characteristics must
      be optimized to achieve stable superhydrophobicity on microscale rough surfaces.
      However, the presence of nanoscale roughness allows a much broader range of
      surface design criteria, decreases the contact angle hysteresis to less than 1
      degrees , and establishes stable and robust superhydrophobicity, although
      nanoscale roughness could not increase the apparent contact angle significantly
      if the microscale roughness dominates.

PMID- 16285793
TI  - Microscopic structure of crystalline Langmuir monolayers of hydroxystearic acids
      by X-ray reflectivity and GID: OH group position and dimensionality effect.
AB  - Hydroxystearic acid (HSA) molecules at the air-water interface present an
      interesting bicompetitive adsorption between primary and secondary hydrophilic
      groups on either end of an alkyl chain, which, depending on the position of the
      second hydrophilic group, may lead to a sharp transition from an expanded phase
      to a crystalline condensed morphology as surface pressure is increased. Here we
      report a set of measurements on a series of hydroxystearic acids in which the
      position of the secondary competing hydrophilic group position is varied along
      the whole extent of the alkyl chain from position 2 (i.e., close to the primary
      hydrophilic group) to positions 7, 9 and 12, the latter being the compounds
      mostly studied in the literature. We show here direct microscopic evidence,
      obtained by synchrotron radiation reflectometry and grazing incidence
      diffraction, that the position of the secondary hydrophilic group not only
      strongly influences the phase diagram as determined by compression isotherms and
      ellipsometry but also induces different crystallization patterns in the 2D system
      of the Langmuir monolayer. In particular, we report for the first time the
      existence of a turning point in the effects of the hydroxyl position on the
      monolayers structure at 7-HSA.

PMID- 16285794
TI  - Adsorption of nitrogen, oxygen, and argon in cobalt(II)-exchanged zeolite X.
AB  - Adsorption of nitrogen, oxygen, and argon on cobalt(II)-exchanged zeolite X at
      288.2 and 303.0 K was studied. The nitrogen and oxygen adsorption capacities
      increase upon cobalt ion exchange up to 71%, beyond which it shows a decreasing
      trend because of the partial degradation of the zeolite structure during the
      cation exchange and high-temperature vacuum dehydration processes. The magnitude
      of the increase in the adsorption capacities for nitrogen is much higher than
      that of oxygen. The nitrogen/oxygen as well as nitrogen/argon selectivities in
      the low-pressure region increase with an increase in cobalt exchange. Marginal
      oxygen selectivity over argon is observed for zeolite samples with higher cobalt
      exchange. The heats of adsorption values for nitrogen and oxygen increase and
      that for argon remain unaffected by cobalt exchange in zeolite X. The very high
      nitrogen adsorption capacity, selectivity, and heat of adsorption in the low
      pressure region for cobalt-exchanged zeolite X compared to the parent sodium form
      of the zeolite show stronger interaction between nitrogen molecules with the
      extraframework cobalt cations of the zeolite. This stronger interaction has been
      explained in terms of the pi-complexation between nitrogen molecules and cobalt
      cations of the zeolites, as confirmed by diffuse reflectance infrared Fourier
      transform spectroscopy, wherein the N[triple bond]N stretching frequency at 2099
      cm(-1) is observed for N2 molecules adsorbed in NaCoX.

PMID- 16285795
TI  - Corner capping of silsesquioxane cages by chemical warfare agent simulants.
AB  - The room-temperature uptake and reactivity of gas-phase methyl dichlorophosphate
      (MDCP) and trichlorophosphate (TCP) within trisilanolphenyl-polyhedral oligomeric
      silsesquioxane (POSS) Langmuir-Blodgett films are investigated. The halogenated
      phosphate molecules are found to readily diffuse into and react with the hybrid
      inorganic-organic silicon-oxide films under ambient conditions. Reflection
      absorption infrared spectroscopy (RAIRS), X-ray photoelectron spectroscopy (XPS),
      and fast atom bombardment-mass spectrometry (FAB-MS) measurements suggest that
      the chlorophosphates undergo hydrolysis with the silanol groups of the POSS LB
      film. Substitution and elimination reactions appear to cap the corner of the POSS
      molecules, leaving a surface-bound phosphoryl group and a resulting structure
      that is highly stable at elevated temperatures.

PMID- 16285796
TI  - Effect of temperature on the buildup of polyelectrolyte multilayers.
AB  - The effect of temperature on the buildup of polyelectrolyte multilayers
      consisting of poly(styrenesulfonate) (PSS), poly(diallyldimethylammonium)
      (PDADMA), and poly(allylamine) (PAH) was studied by using a quartz crystal
      microbalance. The increase of temperature in the deposition process was shown to
      have a considerable effect on the rate of the layer-by-layer buildup. The effect
      of temperature on the PDADMA/PSS deposition was found to be stronger than on the
      PAH/PSS deposition. The increasing temperature was found to extend the
      exponential buildup regime in all of the studied systems. A buildup model was
      created to simulate the buildup and to explain the effect of temperature. The
      model is based on the assumption that each deposition step leads to a quasi
      equilibrium between the concentration of the polymer repeating unit in solution
      and the composition of the layer. According to the model, the layer-by-layer
      buildup is inherently exponential, becoming linear whenever diffusion is not fast
      enough to carry the polymer within the entire thickness of the film. This buildup
      model is discussed jointly with the earlier published three-zone model of the
      polyelectrolyte multilayers. The rate of the buildup is characterized by growth
      exponent beta. The temperature dependence of the growth exponent is discussed in
      connection with the thermodynamic parameters of the deposition.

PMID- 16285797
TI  - Applying Tikhonov regularization to process pendant droplet tensiometry data.
AB  - The problem of obtaining the first and second derivatives of the profile of a
      pendant droplet is formulated as an integral equation of the first kind. This
      equation is solved by Tikhonov regularization in which the method of general
      cross validation is used to guide the selection of the regularization parameter.
      These derivatives are converted into mean curvature as a function of droplet
      height. Surface tension is then obtained by regression computation between the
      mean curvature and two possible algebraic expressions suggested by the Laplace
      Young equation. This way of obtaining surface tension is demonstrated by applying
      it to a number of published droplet profiles. Some of the problems encountered
      are discussed and solutions suggested.

PMID- 16285798
TI  - Direct measurement of the binding force between microfabricated particles and a
      planar surface in aqueous solution by force-sensing piezoresistive cantilevers.
AB  - We propose a force measurement method for evaluating the binding force between
      microscale flat surfaces in an aqueous solution. Using force-sensing
      piezoresistive cantilevers with sub-nanonewton force resolution, we have directly
      measured binding forces between SiO2-SiO2 microcontacts, which were created by
      gravity-driven random collision between microfabricated SiO2 cylindrical
      particles and a planar SiO2 substrate in a HCl solution. First, to examine our
      method we measured the pH dependence of the binding force. The binding forces
      were 12 and 5.8 nN at pH 1.0 and 2.0, respectively. As the pH increased, the
      binding force decreased and became zero at pH greater than 3.0. We confirmed that
      the bindings were based on the van der Waals' (VDW) force at pH 2.0 or less
      whereas a repulsive double-layer force acted between the surfaces at pH 3.0 or
      more. Second, the binding forces were categorized into a friction force or an
      adhesion force between the particles and the substrate. In the measurement, the
      friction force between the particle and the substrate was measured in the case
      when the particle slid on the substrate. On the contrary, the adhesion force was
      measured when the particle came off the substrate. Whether the particle slid or
      came off depended on the aspect ratio of the particle. We fabricated cylindrical
      particles with an aspect ratio of 0.03-2.0 and distinguished the friction force
      from the adhesion force by changing the aspect ratio of the particles. As a
      result, the friction force per unit contact area between SiO2-SiO2 flat surfaces
      was found to be 330 pN/microm2 +/- 20% when we used particles with a low aspect
      ratio (<0.1), and the adhesion force per unit contact area was 90 pN/microm2 +/-
      20% for particles with a high aspect ratio (>0.4). For fluidic self-assembly that
      utilizes microscale surface contact in a liquid, our measurement method is an
      effective tool for studying and developing systems.

PMID- 16285799
TI  - Synthesis and characterization of covalently linked multilayer films prepared in
      the absence of solvent.
AB  - We report the preparation of multilayer organic thin films prepared by sequential
      vapor-phase coupling of monomers. The reactions were carried out at room
      temperature and atmospheric pressure. Films prepared using up to six sequential
      coupling reactions are reported. The following specific vapor-phase reactions
      were found to be viable: reactions between acid chlorides and both aliphatic and
      aromatic amine, hydrolysis reactions, anhydride activation, and reactions between
      anhydrides and primary amines. Homobifunctionalized monomers, such as
      hexamethylenediamine, react primarily via a single endgroup rather than cross
      coupling to the reactive surface via both reactive groups. The estimated coverage
      of the multilayer films is between 36 and 46%. The films were characterized using
      ellipsometric, contact angle, and spectroscopic measurements.

PMID- 16285800
TI  - Analysis of the interfacial properties of fibrillated and nonfibrillated oral
      streptococcal strains from electrophoretic mobility and titration measurements:
      evidence for the shortcomings of the 'classical soft-particle approach'.
AB  - Chemical and structural intricacies of bacterial cells complicate the
      quantitative evaluation of the physicochemical properties pertaining to the cell
      surface. The presence of various types of cell surface appendages has a large
      impact on those properties and therefore on various interfacial phenomena, such
      as aggregation and adhesion. In this paper, an advanced analysis of the
      electrophoretic mobilities of fibrillated and nonfibrillated strains
      (Streptococcus salivarius HB and Streptococcus salivarius HB-C12, respectively)
      is performed over a wide range of pH and ionic strength conditions on the basis
      of a recent electrokinetic theory for soft particles. The latter extends the
      approximate formalism originally developed by Ohshima by solving rigorously the
      fundamental electrokinetic equations without restrictions on the bacterial size,
      charge, and double layer thickness. It further allows (i) a straightforward
      implementation of the dissociation characteristics, as evaluated from titration
      experiments, of the ionogenic charged groups distributed throughout the bacterial
      cell wall and/or the surrounding exopolymer layer and (ii) the inclusion of
      possible specific interactions between the charged groups and ions from the
      background electrolyte other than charge-determining ions. The theory also
      enables an estimation of possible swelling/shrinking processes operating on the
      outer polymeric layer of the bacterium. Application of the electrokinetic model
      to HB and HB-C12 clearly shows a significant discrepancy between the amount of
      surface charges probed by electrophoresis and by protolytic titration. This is
      ascribed to the specific adsorption of cations onto pristine charged sites in the
      cell wall. Physicochemical parameters pertaining to the hydrodynamics (softness
      degree) and electrostatics of the bacterial cell wall (HB-C12) and soft polymeric
      layer (HB) are quantitatively derived.

PMID- 16285801
TI  - Physicochemical characterization of an anatase TiO2 surface and the adsorption of
      a nonionic surfactant: an atomic force microscopy study.
AB  - Atomic force microscopy was used to characterize an anatase TiO2 surface,
      prepared by the helical vapor preparation method. The forces between two bare
      TiO2 surfaces were measured in the presence of water at various pH values. This
      TiO2 isoelectric point (iep) was characterized by the presence of only a van der
      Waals attraction and was measured at pH 5.8; this value is similar to that for a
      rutile TiO2 surface. The adsorption mechanism of a nonionic surfactant molecule
      to this anatase TiO2 surface was investigated by measuring the forces between two
      such TiO2 surfaces at their iep pH in the presence of linear dodecanol
      tetraethoxylate (C12E4), a poly(ethoxylene oxide) n-alkyl ether. C12E4 was seen
      by the presence of steric forces to adsorb to the uncharged TiO2 surface. For low
      surfactant concentrations, C12E4 adsorbed with its hydrophobic tail facing the
      TiO2 substrate, to reduce its entropically unfavorable contacts with water.
      Additional surfactant adsorption occurred at higher surfactant concentrations by
      the hydrophobic and hydrophilic interactions between the surfactant tails and
      heads, respectively, and gave sub-bilayers. A two-step adsorption isotherm was
      subsequently proposed with four regions: (1) submonolayer, (2) complete
      monolayer, (3) sub-bilayer, and (4) bilayer. The absence of a long-range
      repulsive force between the two TiO2 surfaces in the presence of the C12E4
      surface aggregates indicated that a C12E4 nonionic surfactant aggregate did not
      possess charge.

PMID- 16285802
TI  - Aggregation behavior of heteroleptic tris(phthalocyaninato) dysprosium complexes
      with different alkoxy chains in monolayer or multilayer solid films.
AB  - Three heteroleptic tris(phathlocyaninato) dysprosium triple-decker complexes with
      different alkoxy groups at the peripheral positions of the medium phthalocyanine
      ligand (Pc)Dy[Pc(OCnH(2n+1))8]Dy(Pc) (n = 4, 8, 16) (I-III) {Pc = unsubstituted
      phthalocyaninate; Pc(OC4H9)8 = 2,3,9,10,16,17,23,24
      octakis(butyloxy)phthalocyaninate; Pc(OC8H17)8 = 2,3,9,10,16,17,23,24
      octakis(octyloxy)phthalocyaninate; Pc(OC16H33)8 = 2,3,9,10,16,17,23,24
      octakis(hexadecyloxy)phthalocyaninate} have been synthesized, and their aggregate
      behaviors in monolayer and multilayer solid films have been comparatively
      studied. The pure compounds and their 1:4 mixtures with stearic acid (SA) have
      been found to form a stable monolayer at the air/water interface with a tilted
      edge-on orientation of (Pc)Dy[Pc(OCnH(2n+1))8]Dy(Pc) molecules. In the pure
      monolayers of the three triple-decker compounds, wirelike molecular aggregates
      were observed by high-resolution transmission electron microscopy (HRTEM). Adding
      SA has been found to prevent triple-decker compounds (Pc)Dy[Pc(OC4H9)8]Dy(Pc) (I)
      and (Pc)Dy[Pc(OC8H17)8]Dy(Pc) (II) from forming large aggregates, and small
      domains with a diameter of ca. 10 nm were observed in the mixed monolayers. HRTEM
      studies revealed that two crystalline phases with rectangular and hexagonal
      lattice structure are present in the small domains. However, both pi-A isotherms
      and HRTEM studies indicated that the mixed monolayer of compound
      (Pc)Dy[Pc(OC16H33)8]Dy(Pc) (III) with SA did not show a difference from the
      corresponding pure monolayer. The SA molecules were pressed into the cavity above
      the phthalocyanine ring formed by the eight long hexadecyloxy side chains of the
      medium macrocycle ligand in III. The multilayer LB films of all of these triple
      deckers fabricated by the vertical dipping method showed very good layered
      structure as revealed by the multiple-order diffraction peaks in low-angle X-ray
      diffraction (LAXRD) patterns.

PMID- 16285804
TI  - Effect of applied potential on arylmethyl films oxidatively grafted to carbon
      surfaces.
AB  - Arylmethyl films have been grafted to glassy carbon surfaces and to pyrolyzed
      photoresist films (PPFs) by electrochemical oxidation of 1
      naphthylmethylcarboxylate and 4-methoxybenzylcarboxylate. Atomic force microscopy
      (AFM) and electrochemistry were used to characterize the as-prepared films and to
      monitor changes induced by post-preparation treatments. Film thickness was
      measured by depth profiling using an AFM tip to remove film from the PPF surface.
      Surface coverage of electroactive modifiers was estimated from cyclic
      voltammetry, and monitoring the response of a solution-based redox probe at
      grafted surfaces gave a qualitative indication of changes in film properties. For
      preparation of the films, the maximum film thickness increased with the potential
      applied during grafting, and all films were of multilayer thickness. The apparent
      rate of electron transfer for the Fe(CN)(6)3-/Fe(CN)(6)4- couple was very low at
      as-prepared films. After film-grafted electrodes were transferred to pure
      acetonitrile-electrolyte solution and subjected to negative potential excursions,
      the response of the Fe(CN)(6)3-/Fe(CN)(6)4- couple changed and was consistent
      with faster electron-transfer kinetics, the film thickness decreased and the
      surface roughness increased substantially. Applying a positive potential to the
      treated film reversed changes in film thickness, but the voltammetric response of
      the Fe(CN)(6)3-/Fe(CN)(6)4- couple remained kinetically fast. After as-prepared
      films were subjected to positive applied potentials in acetonitrile-electrolyte
      solution, the apparent rate of electron transfer for the Fe(CN)(6)3-/Fe(CN)(6)4-
      couple remained very slow and the measured film thickness was the same or greater
      than that before treatment at positive potentials. Mechanisms are considered to
      explain the observed effects of applied potential on film characteristics.

PMID- 16285805
TI  - On the interactions of ions with the air/water interface.
AB  - In the vicinity of a charged interface, the Poisson-Boltzmann approach considers
      that the ions obey Boltzmann distributions in a mean electrical field that
      satisfies the Poisson equation. However, the boundary between two dielectrics
      generates additional interactions between ions and the interface. The traditional
      models of ion hydration interactions, that assume that water is a homogeneous
      dielectric, predict that these interactions are repulsive for all kinds of ions,
      since all ions should prefer the medium with a larger dielectric constant, where
      they are better hydrated. In reality, the interactions between the ions and the
      neighboring water molecules can generate additional short-range ion-hydration
      interactions, which are either repulsive (for structure-making ions) or
      attractive (for structure-breaking ions). In the present paper, various models
      for the ion-hydration forces are examined and compared with the results of
      molecular dynamics simulations. At large ionic strengths, the latter results
      could be reproduced qualitatively only when short-ranged attractions between the
      structure-breaking ions and the interface were taken into account.

PMID- 16285803
TI  - Microcontact printing of proteins inside microstructures.
AB  - Microfluidic devices are well suited for the miniaturization of biological
      assays, in particular when only small volumes of samples and reagents are
      available, short time to results is desirable, and multiple analytes are to be
      detected. Microfluidic networks (MFNs), which fill by means of capillary forces,
      have already been used to detect important biological analytes with high
      sensitivity and in a combinatorial fashion. These MFNs were coated with Au, onto
      which a hydrophilic, protein-repellent monolayer of thiolated
      poly(ethyleneglycol) (HS-PEG) was self-assembled, and the binding sites for
      analytes were present on a poly(dimethylsiloxane) (PDMS) sealing cover. We report
      here a set of simple methods to extend previous work on MFNs by integrating
      binding sites for analytes inside the microstructures of MFNs using microcontact
      printing (muCP). First, fluorescently labeled antibodies (Abs) were microcontact
      printed from stamps onto planar model surfaces such as glass, Si, Si/SiO2, Au,
      and Au derivatized with HS-PEG to investigate how much candidate materials for
      MFNs would quench the fluorescence of printed, labeled Abs. Au coated with HS-PEG
      led to a fluorescence signal that was approximately 65% weaker than that of glass
      but provided a convenient surface for printing Abs and for rendering the
      microstructures of the MFNs wettable. Then, proteins were inked from solution
      onto the surface of PDMS (Sylgard 184) stamps having continuous or discontinuous
      micropatterns or locally inked onto planar stamps to investigate how the aspect
      ratio (depth:width) of microstructures and the printing conditions affected the
      transfer of protein and the accuracy of the resulting patterns. By applying a
      controlled pressure to the back of the stamp, Abs were accurately microcontact
      printed into the recessed regions of MFNs if the aspect ratio of the MFN
      microstructures was lower than approximately 1:6. Finally, the realization of a
      simple assay between Abs (used as antigens) microcontact-printed in microchannels
      and Abs from solution suggests that this method could become useful to pattern
      proteins in microstructures for advanced bioanalytical purposes.

PMID- 16285806
TI  - Functionalized mesoporous silica films as a matrix for anchoring
      electrochemically active guests.
AB  - Mesoporous silica thin films were shown to be an appropriate matrix for
      immobilization of discrete electroactive moieties, yielding uniform transparent
      thin film electrodes with defined texture and enhanced electrochemical activity.
      The mesoporous silica films prepared on conducting FTO-coated glass substrate
      were postsynthetically functionalized. Alkoxysilanes were used as precursors for
      subsequent grafting via ionic or covalent bonds of representative electroactive
      species, such as polyoxometalate PMo12O(40)3-, hexacyanoferrate(III), and
      ferrocene. The electrochemically active concentration within the silica-based
      composite electrodes achieves 90, 260, and 60 micromol cm(-3) for
      polyoxometalate, hexacyanoferrate(III), and ferrocene, respectively. The amount
      of molecules involved in the charge-transfer sequence is proportional to the film
      thickness and comparable to the total amount of embedded guests. Thus, eventually
      the whole bulk volume of the modified silica films is electrochemically
      accessible. Immobilization in the chemically modified silica matrix alters the
      redox potential of the electroactive molecules. Electron exchange between the
      adjacent redox centers (electron hopping) is proposed as a possible charge
      propagation pathway through the insulating silica matrix, which is supported by
      the fact that the high charge uptake is observed also for the hybrid electrodes
      with the covalently anchored redox guests.

PMID- 16285807
TI  - Nanoparticle-DNA conjugates bearing a specific number of short DNA strands by
      enzymatic manipulation of nanoparticle-bound DNA.
AB  - Self-assembling of metallic nanoparticles to form well-defined nanostructured
      structures is a field that has been receiving considerable research interest in
      recent years. In this field, DNA is a commonly used linker molecule to direct the
      assembly of the nanoscale building blocks because of its unique recognition
      capabilities, mechanical rigidity, and physicochemical stability. This study
      reported our novel approach to generate gold nanoparticle-DNA conjugates bearing
      specially designed DNA linker molecules that can be used as building blocks to
      construct nanoassemblies with precisely controlled structure or as nanoprobes for
      quantitative DNA sequence detection analysis. In our approach, gold nanoparticle
      DNA conjugates bearing a specific number of long double-stranded DNA strands were
      prepared by gel electrophoresis. A restriction endonuclease enzyme was then used
      to manipulate the length of the nanoparticle-bound DNA. This enzymatic cleavage
      was confirmed by gel electrophoresis, and digestion efficiency of 90% or more was
      achieved. With this approach, nanoparticle conjugates bearing a specific number
      of strands of short DNA with less than 20-base can be achieved.

PMID- 16285808
TI  - Biomaterial coatings by stepwise deposition of silk fibroin.
AB  - A completely aqueous, stepwise deposition process with Bombyx mori silk fibroin
      for the assembly of nanoscale thin film coatings is reported the first time. The
      focus of this work was to develop an understanding of the control of this
      deposition process and to characterize the films formed from a physicochemical
      perspective. The deposition process was monitored by UV spectrophotometry and
      research quartz crystal microbalance. Both absorbance and film thickness
      correlated linearly with the number of silk fibroin layers deposited, analogous
      to multilayered materials fabricated from conventional polyelectrolytes. The
      polymer adsorption process was stable and reproducible, with control of a single
      layer thickness ranging from a few to tens of nanometers, determined by the
      concentrations of silk fibroin, salt concentration in the dipping solution, and
      method of rinsing. The driving force for the assembly of silk fibroin onto the
      substrate was primarily hydrophobic interactions, while some electrostatic
      interactions were also involved. The difference with this approach from
      traditional polyelectrolyte layer-by-layer techniques is that an intervening
      drying step is used to control the structure and stability of the self-assembled
      silk fibroin. The assembled films were stable under physiological conditions and
      supported human bone marrow stem cell adhesion, growth, and differentiation. This
      approach offers new options to engineer biomaterial coatings as well as bulk
      materials with control of both interfacial properties conducive to specific
      cellular or tissue responses and the potential to entrap and deliver labile
      molecules or other components due to the all-aqueous process described.

PMID- 16285809
TI  - Ligand-receptor interactions in tethered polymer layers.
AB  - The binding of small proteins to ligands that are attached to the free ends of
      polymers tethered to a planar surface is studied using a molecular theory. The
      effects of changing the intrinsic binding equilibrium constant of the ligand
      receptor pair, the polymer surface coverage, the polymer molecular weight, and
      the protein size are studied. The results are also compared with the case where
      ligands are directly attached to the surface without a polymer acting as a
      spacer. We found that within the biological range of binding constants the
      protein adsorption is enhanced by the presence of the polymer spacers. There is
      always an optimal surface coverage for which ligand-receptor binding is a
      maximum. This maximum increases as the binding energy and/or the polymer
      molecular weight increase. The presence of the maximum is due to the ability of
      the polymer-bound proteins to form a thick layer by dispersing the ligands in
      space to optimize binding and minimize lateral repulsions. The fraction of bound
      receptors is unity for a very small surface coverage of ligands. The very sharp
      decrease in the fraction of bound ligand-receptor pairs with surface coverage
      depends on the polymer spacer chain length. We found that the binding of proteins
      is reduced as the size of the protein increases. The orientation of the bound
      proteins can be manipulated by proper choice of the grafted layer conditions. At
      high polymer surface coverage the bound proteins are predominantly perpendicular
      to the surface, while at low surface coverage there is a more random distribution
      of orientations. To avoid nonspecific adsorption on the surface, we studied the
      case where the surface is covered by a mixture of a relatively high molecular
      weight polymer with a ligand attached to its free end and a low molecular weight
      polymer without ligand. These systems present a maximum in the binding of
      proteins, which is of the same magnitude as when only the long polymer-ligand is
      present. Moreover, when the total surface coverage in the mixed layers of
      polymers is high enough, nonspecific adsorption of the proteins on the surface is
      suppressed. The use of the presented theoretical results for the design of
      surface modifiers with tailored abilities for specific binding of proteins and
      optimal nonfouling capabilities is discussed.

PMID- 16285810
TI  - Heat-stabilized phospholipid films: film characterization and the production of
      protein-resistant surfaces.
AB  - Phospholipid films have been shown in a number of studies to exhibit potential as
      nonfouling surfaces for biomaterial applications. However, the practical
      application of such films has been hindered by instability in aqueous solutions
      and significant detachment under mild shear stresses. Methods for stabilizing
      lipid films have been investigated, but to date require the presence of specific
      functional groups or chemical modification of the lipid molecule. In contrast to
      these methods, we present a process for heat-stabilization of lipid films. These
      heat-stabilized films have been shown to be able to withstand repeated rinsing
      without significant detachment. Phosphatidylcholine monolayers were formed on
      hydrophobic self-assembled monolayers using the liposome fusion method and
      stabilized at 80 degrees C. The films were characterized using Fourier transform
      infrared spectroscopy, ellipsometry, and atomic force microscopy and were shown
      to be defect free after repeated rinsing. Further experiments using a quartz
      crystal microbalance showed that the heat-stabilized lipid films were highly
      resistant to nonspecific protein adhesion and compared very favorably with
      poly(ethylene glycol)-coated surfaces under identical exposure conditions.

PMID- 16285811
TI  - Force-induced de-adhesion of specifically bound vesicles: strong adhesion in
      competition with tether extraction.
AB  - A theoretical study of the thermodynamic equilibrium between force-induced tether
      formation and the adhesion of vesicles mediated by specific ligand-receptor
      interactions has been performed. The formation of bonds between mobile ligands in
      the vesicle and immobile receptors on the substrate is examined within a
      thermodynamic approximation. The shape of a vesicle pulled with a point force is
      calculated within a continuous approach. The two approaches are merged self
      consistently by the use of the effective adhesion potential produced by the
      collective action of the bonds. As a result, the shapes of the vesicle and the
      tether, as well as the number of formed bonds in the contact zone, are determined
      as a function of the force, and approximate analytic expressions for them are
      provided. The de-adhesion process is characterized by the construction of a phase
      diagram that is a function of the density of the ligands in the vesicle, the
      surface coverage by receptors, the ligand-receptor binding affinity, and the
      reduced volume of the vesicle. In all cases, the phase diagram contains three
      regions separated by two nonintersecting lines of critical forces. The first is
      the line of onset forces associated with a second-order shape transition from a
      spherical cap to a tethered vesicle. The second line is attributed to the
      detachment forces at which a first-order unbinding transition from a tethered
      shape to a free vesicle occurs.

PMID- 16285812
TI  - Nonionic surfactant sorption onto the bacterial cell surface: a multi-interaction
      isotherm.
AB  - The adsorption of linear polyoxyethylene (POE) alcohol surfactants of the form
      CxEy onto the surface of a Sphingomonas sp. has been examined. For this study,
      the alkyl chain length (x) was fixed at 12 and the POE chain length (y) was
      varied, with y = 4, 7, 9, 10, and 23 ethylene oxide units. Langmuirian isotherms
      were observed for C12E4 and C12E23, and more complex isotherms were observed for
      the three intermediate POE chain length surfactants, with C12E7 and C12E9
      exhibiting strong S-shaped isotherms. All isotherms showed plateaus near the
      critical micelle concentration (CMC) with the plateau decreasing with increasing
      POE chain length. A simple multi-interaction isotherm is proposed that models the
      sorption isotherm as the sum of two interactions. The first interaction describes
      monolayer adsorption, whereas the second interaction describes lateral
      interactions between sorbed surfactant molecules and the formation of surface
      aggregates. Varying ratios of these two interactions as a function of POE chain
      length gives rise to the variety of observed isotherm shapes. Results of the
      isotherm analysis suggest that lateral interactions dominate for surfactants with
      low POE chain lengths, and the lateral interactions decrease as the POE chain
      length is increased.

PMID- 16285813
TI  - Are conformational changes, induced by osmotic pressure variations, the
      underlying mechanism of controlling the adhesive activity of mussel adhesive
      proteins?
AB  - The mussel adhesive protein Mefp-1, under physiological conditions, presumably
      has a self-avoiding random walk conformation with helix-like or turned deca
      peptide segments. Such a conformation may coil up under osmotic pressure induced
      by surrounding macromolecules. As a consequence, the orientation of the 3,4
      dihydroxy-phenylalanine groups (dopa), essential for the adhesive strength as
      well as the cohesive strength in Mefp-1, will be altered. Changing the
      concentration of the protein itself or of different-type surrounding
      macromolecules may therefore be a tool to control the protein's adhesive
      activity. The effect of osmotic pressure on the conformation and dopa reactivity
      of Mefp-1 is studied by the addition of (poly)ethylene oxide (PEO) as a model
      macromolecule (Mw = 100 kD). From UV-spectroscopy measurements, it can be
      concluded that dopa reactivity in Mefp-1 changes with increasing PEO
      concentration. Fitting of the measured absorbance intensity data of the oxidation
      product dopaquinone versus time with a kinetic model points to the decreased
      accessibility of dopa groups in the Mefp-1 structure, a faster oxidation, and
      diminished cross linking under the influence of increasing PEO concentration up
      to 2.4 g/L, corresponding to an osmotic pressure of approximately 73 Pa. At
      higher PEO concentrations, the accessibility of the dopa groups for oxidation as
      well as cross-link formation decreases until about 20% of the dopa groups are
      oxidized at a PEO concentration of 3.8 g/L, corresponding to an osmotic pressure
      of approximately 113 Pa. FTIR measurements on the basis of amide I shifts
      qualitatively point to a transition to a more continuously turned structure of
      Mefp-1 in the presence of PEO. Therefore, it seems that conformational changes
      caused by variations of osmotic pressure determine the extent of steric hindrance
      of the dopa groups and hence the adhesive reactivity of Mefp-1.

PMID- 16285814
TI  - Interactions between denatured milk serum proteins and casein micelles studied by
      diffusing wave spectroscopy.
AB  - The acid-induced aggregation of casein micelles from milk, in the presence of
      different whey protein preparations from heated and unheated milk, has been
      studied using diffusing wave spectroscopy (DWS). In particular, the study focused
      on the turbidity (or l*) parameter obtainable from DWS, which can give
      information on the interactions between particles in aggregating systems. The
      experiments provided evidence that the presence of small, soluble, whey
      protein/kappa-casein aggregates derived from heated milk gave rise to
      interactions with both heated and unheated casein micelles over a pH range of 5.6
      down to 5.2. Comparison of heated and unheated milks, together with milks whose
      sera had been exchanged, showed that direct interactions were indeed occurring,
      even between untreated casein micelles and soluble whey protein complexes.
      Comparison of the behavior of the whey protein aggregates in emulsion
      preparations where they could not interact with the large particles confirmed
      that the effect was specific to the presence of casein micelles and could not
      arise simply from the aggregation of the whey proteins themselves.

PMID- 16285815
TI  - Silver nanoparticle formation in microemulsions acting both as template and
      reducing agent.
AB  - A novel method of making silver nanoparticles in water-in-oil microemulsions
      using the surfactants as both the reducing agent and as the structure-directing
      agent is presented. Since no external strong reducing agent is used the kinetics
      of the formation is slow, which makes it possible to study the silver
      nanoparticle formation in situ. The microemulsions used were based on either the
      nonionic surfactant Brij30 (C12E4), which reduces the silver ion to metallic
      silver and is thereby partly oxidized, or mixtures of Brij30 and AOT (sodium
      bis(2-ethylhexyl) sulfosuccinate, where the latter does not reduce the silver
      ions. The influences of silver ion and nonionic surfactant concentrations on the
      formation kinetics of the nanoparticles were followed in situ using UV-vis
      spectroscopy, and both parameters were found to have a big influence. The
      microemulsion droplet's size, size distribution, and shape were examined by small
      angle X-ray scattering (SAXS), and the formed silver nanoparticles were studied
      using both transmission electron microscopy and SAXS. The SAXS measurements
      showed that the presence of silver nitrate does not affect the microemulsion
      systems noticeably and that the droplet's size and shape are retained during the
      particle formation. It is shown that the size and morphology of the particles do
      not directly follow the shape and size of the microemulsion droplets even though
      there is a relation between the droplet size and the radii of the formed
      particles.

PMID- 16285816
TI  - Visible light photocatalysis with platinized rutile TiO2 for aqueous organic
      oxidation.
AB  - Platinized rutile TiO2 samples containing varying concentrations of Pt were
      synthesized using Kemira (KE, BET surface area 50 m2/g, from Finland), and Toto
      HT0270 (HT, BET surface area 2.9 m2/g, from Japan) as the starting materials by
      solution mixing followed by sintering the precursors. Photocatalytic activities
      were established for phenol oxidation under visible light (wavelength >400 nm).
      Our results show optimal performance for 8 wt % platinized KE (8 wt % Pt/KE) and
      (1/2) wt % platinized HT rutile samples. The specific roles of O2 and visible
      light were examined using the 8 wt % Pt/KE sample in either N2 gas ambient or no
      illumination. Separately, 8 wt % platinized SiO2 was tested to compare its
      performance with that of platinized rutile TiO2. Several other chemicals
      containing different functional groups (formic acid, salicylic acid, 4
      chlorophenol, 2,4,6-trichlorophenol, diethyl phosphoramidate) were selected for
      photooxidation tests with (1/2) wt % platinized HT rutile. X-ray diffraction
      reveals Pt metal clusters segregating on the surface of rutile TiO2 particles
      with increasing Pt weight percent. The Pt cluster surface area broadly increases,
      while the effective optical band gap steadily decreases with platinization of the
      rutile samples. These results suggest that Pt clusters on the surface of rutile
      TiO2 particles serve to mediate electron transfer from rutile to O2, thus
      facilitating photooxidation of organic chemicals.

PMID- 16285817
TI  - Broad-band antireflection coating at near-infrared wavelengths by a breath
      figure.
AB  - We prepared a porous thin film by spin-coating of a cellulose acetate butyrate
      (CAB) solution in tetrahydrofuran under a humid environment. Due to evaporative
      cooling during spin-coating, condensed water droplets were formed by a breath
      figure on the CAB solution, and these developed a porous structure after complete
      drying. By varying the solution concentration and rotating speeds, two distinct
      morphologies were generated: top and bottom layers with higher and lower
      porosities, respectively. We found that the two-layer porous film coated on glass
      exhibited low reflectance of less than 1% in the near-infrared (NIR) regime
      corresponding to wavelengths between 900 and 2200 nm. Since the porous structure
      was very uniform over a large area, the film could be easily employed for broad
      band antireflection coating at NIR wavelengths.

PMID- 16285818
TI  - Structure factors of dispersible units of carbon black filler in rubbers.
AB  - We report the structures of dispersible units, a most fundamental but minimal
      dispersible structural unit of a carbon black (CB) filler that is formed in two
      kinds of rubber (polyisoprene and styrene-butadiene random copolymer) matrices
      under a given processing condition. The results obtained from various small-angle
      scattering techniques showed that the CB aggregates, as observed after the
      sonification of a CB/toluene solution, were a spherical shape composed of
      approximately nine primary CB particles fused together. In the rubber matrices,
      the aggregates clustered into higher order structures defined in this work as the
      dispersible units, which are the fundamental structural elements (or the "lower
      cutoff structures") that build up a higher order mass-fractal structure.
      Furthermore, we found that the morphology of the dispersible units strongly
      depended on the rubber matrix, although the mass-fractal dimensions remained
      unchanged.

PMID- 16285819
TI  - Investigation of cation-induced degradation of dye-sensitized solar cells for a
      new strategy to long-term stability.
AB  - Current-voltage characteristics, electron lifetimes (tau), and electron diffusion
      coefficients (D) of dye-sensitized TiO2 solar cells (DSCs) composed of liquid
      electrolytes were repeatedly measured over a period of time. It was found that
      the energy conversion efficiency of the DSCs using electrolytes composed of Li+
      or tetrabutylammonium cation as the counter charges of I-/I3- redox couples
      decreased with the lapse of time. On the other hand, such a decrease was not
      observed for the DSC consisting of 1,2-dimethyl-3-propylimidazolium cation or of
      Li+ coupled with the addition of tert-butylpyridine. The decrease of the
      efficiency was in accordance with a decreased electron lifetime. The notable
      decrease in the presence of Li+ is probably caused by the excess amount of Li+
      adsorption on the TiO2 surface.

PMID- 16285820
TI  - Hydrogen storage in nanostructured carbons by spillover: bridge-building
      enhancement.
AB  - The hydrogen storage capacity in nanostructured carbon materials can be increased
      by atomic hydrogen spillover from a supported catalyst. A simple and effective
      technique was developed to build carbon bridges that serve to improve contact
      between a spillover source and a secondary receptor. In this work, a supported
      catalyst (Pd-C) served as the source of hydrogen atoms via dissociation and
      primary spillover and AX-21 or single-walled carbon nanotubes (SWNTs) were
      secondary spillover receptors. By carbonizing a bridge-forming precursor in the
      presence of the components, the hydrogen adsorption amount was increased by a
      factor of 2.9 for the AX-21 receptor and 1.6 for the SWNT receptor at 298 K and
      100 kPa. Similar results were obtained at 10 MPa, indicating that the enhancement
      factor is a weak function of pressure. The AX-21 receptor with carbon bridges had
      the highest absolute capacity of 1.8 wt % at 298 K and 10 MPa. Reversibility was
      demonstrated through desorption and readsorption at 298 K. The bridge-building
      process appears to be receptor specific, and optimization may yield even greater
      enhancement. Using this technique, enhancements in storage of up to 17-fold on
      other carbon-based materials have been observed and will be reported elsewhere
      shortly.

PMID- 16285821
TI  - Substrate-independent approach for polymer brush growth by surface atom transfer
      radical polymerization.
AB  - A simple method for growing polymer brushes by atom transfer radical
      polymerization (ATRP) off solid surfaces has been devised. This entails pulsed
      plasmachemical deposition of a halogen-containing initiator layer, followed by
      either organic or aqueous phase controlled surface polymerization. The wide-scale
      applicability of this approach is exemplified by functionalizing flat substrates,
      microbeads, and nonwoven textiles.

PMID- 16285822
TI  - Overcharging of polyelectrolyte complexes by the guest polyelectrolyte studied by
      fluorescence spectroscopy.
AB  - Polyion complexes (PICs) of anionic block copolymer poly(ethylene oxide)-block
      poly(sodium methacrylate), PEO-block-(PMA)Na, and a cationic homopolymer,
      poly((methacryloyloxyethyl)trimethylammonium chloride), PMOTAC, have been studied
      by fluorescence spectroscopy. Pyrene and naphthalene singly labeled block
      copolymers were used with two different sodium methacrylate block lengths. The
      chain exchange between the stoichiometric PICs at the equilibrium state and the
      formation of the negatively charged PICs on addition of excess PEO-block-(PMA)Na
      to stoichiometric PIC solution were of interest. The chain exchange between the
      stoichiometric complexes was observed to occur via two mechanisms. The faster
      chain exchange occurs via insertion and expulsion of single chains, while merging
      and splitting of the PIC particles is behind the slower chain exchange event.
      Incorporation of an excess amount of the guest polyion into a stoichiometric PIC
      took place on further addition of the PEO-block-(PMA)Na. The same mechanisms were
      recognized in the overcharging process of the PICs as in the chain exchange
      between the stoichiometric PICs.

PMID- 16285823
TI  - Controlling porosity within colloidal heteroaggregates.
AB  - Heteroaggregates of cationic poly(2-vinylpyridine) microgels and anionic
      polystyrene latex particles have been made by mixing dilute, aqueous suspensions.
      The growth of the heteroaggregates was arrested by the addition of anionic silica
      particles that adsorbed to the free surface of the cationic microgel particles.
      The resulting heteroaggregates were then concentrated by vacuum filtration,
      freeze-dried, and characterized by mercury porosimetry and electron microscopy.
      The inclusion of soft, deformable microgels resulted in heteroaggregates with
      higher porosity than obtained with heteroaggregates of anionic and cationic latex
      particles. Control of the pore volumes within the freeze-dried filter cakes was
      demonstrated by two approaches. In the first approach, heteroaggregation at a
      constant KCl concentration of 0.01 mM was arrested at different times after
      mixing the latex and microgel particles, thereby limiting the size of the
      aggregates. The porosity of the resulting filter cake increased from 61 to 65 vol
      % as the aggregation time increased from 15 to 120 s. In the second technique,
      the aggregation time prior to arrest was maintained at 120 s while the KCl
      concentration was varied between 0.01 and 10 mM. The pore volume of the
      aggregates decreased from 65 to 57 vol % as the electrolyte concentration
      increased, a trend explained in terms of the effect of the Debye length on the
      aggregation process.

PMID- 16285824
TI  - Poly(ethylene glycol)--oligolactates with monodisperse hydrophobic blocks:
      preparation, characterization, and behavior in water.
AB  - Methoxypoly(ethylene glycol)-b-oligo-L-lactate (mPEG-b-OLA) diblock oligomers
      with monodisperse OLA blocks were obtained by fractionation of polydisperse block
      oligomers using preparative HPLC. The fractionated oligomers were composed of an
      mPEG block with a molecular weight of 350, 550, or 750 and an OLA block with a
      degree of polymerization of 4, 6, 8, or 10. The diblock oligomers with a low PEG
      content were fully amorphous, with glass transition temperatures ranging from -60
      to -20 degrees C, indicating that the blocks were miscible. Upon heating aqueous
      dispersions of the block oligomers, cloud points, depending on the PEG/OLA ratio
      of the block oligomer, were observed at temperatures above 40 degrees C. The
      monodispersity of the hydrophobic block enabled the amphiphilic molecules to form
      nanoparticles in water with a hydrodynamic radius of 130-300 nm, at
      concentrations above the critical aggregation concentration (0.4-1 mg/mL),
      whereas polydisperse mPEG-b-OLAs gave formation of large aggregates. Static light
      scattering measurements showed that the nanoparticles have a low density (0.6-25
      mg/mL), indicating that the particles are highly hydrated. In agreement herewith,
      the (1)H NMR spectra of nanoparticles in D2O closely resembled spectra in a good
      solvent for both blocks (CDCl3). It is therefore suggested that the nanoparticles
      contain a hydrated core of mPEG-b-OLA block oligomers, stabilized by a thin outer
      PEG layer. The particles were stable for two weeks, except for the mPEG350 series
      and mPEG750-b-OLA4, indicating that both the PEG block size and the PEG weight
      fraction of the oligomers determine their stability. The evident self-emulsifying
      properties of mPEG-b-oligo-l-lactates with monodisperse hydrophobic blocks as
      demonstrated in this study, together with their expected biocompatibility and
      biodegradability, make these systems well suitable for pharmaceutical
      applications.

PMID- 16285825
TI  - Surface plasmon resonance study of the interaction of a beta-cyclodextrin polymer
      and hydrophobically modified poly(N-isopropylacrylamide).
AB  - Surface plasmon resonance (SPR) technique is used to follow, both in real time
      and in situ, the association between a physically adsorbed polymer of beta
      cyclodextrin (pbetaCD) and different hydrophobically modified poly(N
      isopropylacrylamide) (PNIPAM) copolymers containing either adamantyl or dodecyl
      groups. This association is due to the complex formation between the hydrophobic
      groups and the betaCD cavities. Therefore, the adsorbed amount of PNIPAM onto the
      pbetaCD layer depends on the substituent and on its substitution level. The
      association and dissociation rate constants are evaluated from the kinetics of
      PNIPAM adsorption. An estimation of the association constants leads to values
      higher than 10(4) M(-1), reflecting the strong interaction between these
      polymers.

PMID- 16285826
TI  - pH-induced reversible conformational and morphological regulation of polyleucine
      grafted polyallylamine assembly in solution.
AB  - One of the essential parts in the molecular mechanism of biological properties is
      the structural changes of proteins induced by stimuli. An amphiphilic copolymer,
      poly(L-leucine) grafted polyallylamine as a simple model of proteins, has been
      prepared by NCA polymerization with free amino groups of polyallylamine as an
      initiator. Here, we report the pH-induced reversible conformational and
      morphological regulation of the amphiphilic copolymer, whose hydrophobic peptide
      graft chains have no pH-sensitive groups, in an aqueous solution containing 50
      vol % trifluoroethanol. The conformation of the poly(L-leucine) graft chain was
      found to be strongly pH dependent. Under acidic conditions, where electrostatic
      repulsion existed between the neighboring protonated amine moieties of the
      polyallylamine main chain, the rapid aggregation of the poly(l-leucine) graft
      chains was disturbed, and the peptide graft chains formed a beta-sheet structure
      owing to the intramolecular hydrogen bonding among the graft chains. Under this
      condition, the amphiphilic polymer formed amyloid-like fibrils, and then the
      fibrils grew into a planer plate composed of staked beta-sheets. On the other
      hand, under basic conditions, the poly(L-leucine) graft chains showed
      conformational transitions from a beta-sheet structure to an alpha-helical
      conformation owing to a distortion of the regular arrangement of the peptide
      graft chains by the conformational change of the polyallylamine main chain, whose
      amino groups were deprotonated. The conformational transition resulted in a
      disturbance of the regular sheet assembly of the amphiphilic copolymer and
      induced morphological changes to the amorphous globular aggregates. The pH
      induced conformational and morphological changes of the poly(L-leucine) graft
      polyallylamine were reversible and synchronized with the protonation of the
      polyallylamine main chain.

PMID- 16285827
TI  - Single-crystalline platinum nanosheets from nonionic surfactant 2-D self
      assemblies at solid/aqueous solution interfaces.
AB  - Single-crystalline platinum nanosheets have been prepared via a new methodology
      based on the chemical reduction of a platinum salt (H2PtCl6) with hydrazine at a
      graphite/solution interface, using polyoxyethylene (20) sorbitan monostearate
      (Tween 60) based self-assembly (hemicylindrical micelle) templates. The platinum
      nanosheets with a uniform thickness of as thin as 3.5 +/- 1 nm are surface-smooth
      and continuous over relatively large length scales of micrometer sizes. In
      striking contrast to the Tween 60 based system, no Pt nanosheets are obtained
      with nonaethylene glycol monododecyl ether (C12EO9) and polyoxyethylene (23)
      dodecyl ether (C12EO23). No Pt nanosheets are also obtainable with a laterally
      homogeneous layer of Tween 60 formed at the silica/solution interface. These
      results indicate that surfactant Tween 60 molecules with a triple polyoxyethylene
      structure, as well as their hemicylindrical micelle templates, play an essential
      role for the formation of the Pt nanosheets. It is also suggested that the
      interfacially directed growth of Pt metals within the aqueous shells of the Tween
      60 hemicylindrical micelles induces the thin Pt crystals as thick as the aqueous
      shells. The present approach could be extended to prepare a wide range of novel
      nanostructures of noble metals, using various micelle-like self-assemblies at
      interfaces.

PMID- 16285828
TI  - PtRu/carbon nanotube nanocomposite synthesized in supercritical fluid: a novel
      electrocatalyst for direct methanol fuel cells.
AB  - Platinum/ruthenium nanoparticles were decorated on carbon nanotubes (CNT) in
      supercritical carbon dioxide, and the nanocomposites were characterized by
      transmission electron microscopy (TEM) and X-ray diffraction (XRD). TEM images
      show that the particles size is in the range of 5-10 nm, and XRD patterns show a
      face-centered cubic crystal structure. Methanol electrooxidation in 1 M sulfuric
      acid electrolyte containing 2 M methanol were studied onPtRu/CNT (Pt, 4.1 wt%;
      Ru, 2.3 wt%; molar ratio approximately Pt/Ru = 45:55) catalysts using cyclic
      voltammetry, linear sweep voltammetry, chronoamperometry, and electrochemical
      impedance spectroscopy. All the electrochemical results show that PtRu/CNT
      catalysts exhibit high activity for methanol oxidation which resulted from the
      high surface area of carbon nanotubes and the nanostructure of platinum/ruthenium
      particles. Compared with Pt/CNT, the onset potential is much lower and the ratio
      of forward anodic peak current to reverse anodic peak current is much higher for
      methanol oxidation, which indicates the higher catalytic activity of PtRu/CNT.
      The presence of Ru with Pt accelerates the rate of methanol oxidation. The
      results demonstrated the feasibility of processing bimetallic catalysts in
      supercritical carbon dioxide for fuel cell applications.

PMID- 16285829
TI  - Influence of a water rinse on the structure and properties of poly(3,4-ethylene
      dioxythiophene):poly(styrene sulfonate) films.
AB  - Poly(3,4-ethylene dioxythiophene):poly(styrene sulfonic acid) (PEDOT:PSS) films
      exhibit a complex structure of interconnected conductive PEDOT domains in an
      insulating PSS matrix that controls their electrical properties. This structure
      is modified by a water rinse, which removes PSS with negligible PEDOT loss. Upon
      PSS removal, film thickness is reduced by 35%, conductivity is increased by 50%,
      and a prominent dielectric relaxation is eliminated. These results suggest that
      the removed PSS is not associated with PEDOT and that the conductive domain
      network is not substantially altered by the removal of a significant fraction of
      insulator. The removal of PSS may benefit organic light emitting diode
      fabrication by reducing acid attack on indium tin oxide electrodes and lead to
      more robust performance in switching circuits by extending the working frequency
      range.

PMID- 16285830
TI  - Formation mechanism of conducting polypyrrole nanotubes in reverse micelle
      systems.
AB  - Polypyrrole (PPy) nanotubes were readily fabricated through chemical oxidation
      polymerization in sodium bis(2-ethylhexyl) sulfosuccinate (AOT) reverse (water-in
      oil) emulsions. The reverse cylindrical micelle phase was characterized, and the
      key factors affecting the formation of PPy nanotubes were systematically
      inspected. AOT reverse cylindrical micelles were prepared via a cooperative
      interaction between an aqueous FeCl3 solution and AOT in an apolar solvent. In
      the H2O/FeCl3/AOT/apolar solvent system, the aqueous FeCl3 solution played a role
      in increasing the ionic strength and decreasing the second critical micelle
      concentration of AOT. As a result, AOT reverse cylindrical micelles could be
      spontaneously formed in an apolar solvent. In addition, iron cations were
      adsorbed to the anionic AOT headgroups that were capable of extracting metal
      cations from the aqueous core. Under these conditions, the addition of pyrrole
      monomer resulted in the chemical oxidation polymerization of the corresponding
      monomer at the surface of AOT reverse cylindrical micelles, followed by the
      formation of tubular PPy nanostructures. In a typical composition (74.0 wt %
      hexane, 22.4 wt % AOT, and 3.6 wt % aqueous FeCl3 solution at 15 degrees C), the
      average diameter of PPy nanotubes was approximately 94 nm and their length was
      more than 2 mum. The PPy nanotube dimensions were affected by synthetic variables
      such as the weight ratio of aqueous FeCl3 solution/AOT, type of apolar solvent,
      and reaction temperature. Moreover, the relationship between the diameter and the
      conductivity of the nanotubes was investigated.

PMID- 16285831
TI  - van der Waals layer-by-layer construction of a carbon nanotube 2D network.
AB  - The acid-treated single-walled carbon nanotubes (SWCNTs) dispersed in water are
      only kinetically stable with electrostatic double layer repulsions just balancing
      against van der Waals (VDW) attractions. Introducing any external factor to
      disturb this balance causes immediate coagulation of SWCNTs. Here, an amine
      covered flat substrate was immersed in the dispersion to initiate adsorption of
      SWCNTs onto the substrate surface. By repeating an adsorption-rinse-dry cycle, it
      was possible to deposit SWCNT bundles in a layer-by-layer fashion and to develop
      a 2D network consisting only of SWCNTs that are held by VDW interaction. We show
      that (1) adsorbed solution-grown aggregates are not relevant for the network
      connectivity, (2) 2D percolation takes place at very low surface coverage, (3)
      the electrical resistivity follows a power law against the layering cycles, (4)
      not only the adsorbed amount but also the added amount per layering cycle
      increases linearly with the SWCNT concentration, and (5) after the adsorption is
      initiated by amines, VDW attraction takes over for subsequent adsorption, with
      the consequence that the newly adsorbed SWCNTs are used to thicken each arm of
      the network rather than to cover more free surfaces.

PMID- 16285833
TI  - Rigid, superparamagnetic chains of permanently linked beads coated with magnetic
      nanoparticles. Synthesis and rotational dynamics under applied magnetic fields.
AB  - An inexpensive and versatile approach is reported for the synthesis of
      monodisperse magnetoresponsive rods of desired diameter, length, and magnetic
      susceptibility based on the confined alignment of magnetic beads in microchannels
      of selected channel height, followed by localized hydrolysis of sol-gel
      precursors within polyelectrolyte shells adsorbed on the beads. The layer-by
      layer technique was used to coat the polystyrene beads with polyelectrolytes of
      alternating charge and with charged magnetic nanoparticles, and the polystyrene
      cores could be removed either by solvent dissolution or by calcination to form
      hollow-shelled chains. The reorientation dynamics of single and clustered chains
      following the application of an external magnetic field was evaluated
      theoretically, with favorable comparisons with the experimental data.

PMID- 16285834
TI  - Synthesis of colloidal silica dumbbells.
AB  - We describe the synthesis and characterization of stable suspensions of
      monodisperse fluorescently labeled silica dumbbell particles. Pure dispersions of
      silica dumbbells with center-to-center lengths from 174 nm to 2.3 microm were
      produced with a variety of aspect ratios. Individual particles in concentrated
      dispersions of these particles could be imaged with confocal microscopy. These
      particles can be used as a colloidal model system for addressing fundamental
      questions about crystal and glass formation of low-aspect-ratio anisotropic
      particles. They also have potential in photonic applications and electro-optical
      devices.

PMID- 16285835
TI  - Shear ordering in thin films of spherical block copolymer.
AB  - We have investigated shear-induced alignment of a bilayer of spherical diblock
      copolymer micelles within thin films using molecular dynamics simulations at two
      different levels of coarse-graining. At the microscopic level, the copolymers are
      modeled as bead and spring chains with specific interaction potentials which
      produce strongly segregated spherical micelles. The simulations qualitatively
      reveal that long-range shear-induced ordering of hexagonally arranged micelles
      arises because of the tendency of micelles to pursue trajectories of minimum
      frictional resistance against micelles in the opposing layer. This influences
      their alignment in the direction of shear without them breaking apart and
      reforming within the time scale of the simulations. As observed in experiments,
      the ordering is shown to be very sensitive to the film thickness and shearing
      rates. To access larger lengths and longer time scales, we further coarse-grain
      our system to a mesoscopic level where an individual micelle is represented by a
      spherical particle, which interacts with other micelles through an effective
      potential obtained from the microscopic simulations. This approach enables us to
      follow the time evolution of global order from locally ordered domains. An
      exponentially fast growth of the orientational correlation length of the
      hexagonal pattern at early times, followed by a crossover to linear growth, is
      found in the presence of shear, in contrast to the much slower power-law scalings
      observed in experiments without shear.

PMID- 16285832
TI  - pH-responsive capsules derived from nanocrystal templating.
AB  - In the current work we demonstrate a facile and versatile way to create
      hydrophilic polymeric capsules by integration of Au nanocrystal templating,
      surface-initiated atom-transfer radical polymerization, and selective chemical
      cross-linking of polymer shells. Capsules of the homopolymer of 2
      (dimethylamino)ethyl methacrylate and its copolymers with 2-(diethylamino)ethyl
      methacrylate and poly(ethylene glycol) methyl ether methacrylate were
      constructed. They swell at low pH and shrink at high pH. On the basis of the pH
      sensitivity of the resulting capsules, encapsulation and release of a drug model,
      rhodamine 6G, were realized. Furthermore, by cleaving Au-S bonds between Au cores
      and polymer shells, capsules containing free Au cores were generated, paving a
      simple pathway to introduce more functionality to the polymeric capsules.

PMID- 16285836
TI  - Coagulation of nanoparticles in reverse micellar systems: a Monte Carlo model.
AB  - The process of formation of nanoparticles obtained by mixing two micellized,
      aqueous solutions has been simulated using the Monte Carlo technique. The model
      includes the phenomena of finite nucleation, growth via intermicellar exchange,
      and coagulation of nanoparticles after their formation. Using the model, an
      exploratory study has been conducted to analyze whether the coagulation of
      nanoparticles is the reason for the formation of nanoparticles whose sizes are
      comparable to the size of the reverse micelles. The model explains the possible
      mechanism of coagulation of semiconductor nanoparticles formed within reverse
      micelles and its effect on the evolution of their size with time. The model is
      predictive in nature, and the simulation results compare well with those observed
      experimentally.

PMID- 16285837
TI  - Modeling of confinement-induced phase transitions for surfactant layers on
      amphiphilic surfaces.
AB  - A self-consistent field model is used to consider a solution of positively
      charged surfactants up to its critical micellization concentration adsorbing onto
      two surfaces in close proximity. Each surface mimics a polystyrene sulfonate
      interface; that is, hydrophobic properties are combined with a (fixed) negative
      charge. We observe large and sudden changes in adsorption as a function of
      separation, which are not normally considered when interpreting surface force
      measurements. The parameters are chosen such that the adsorbed surfactant layer
      is of a monolayer type when the surfaces are far apart. A typical interaction
      curve is presented for a fixed surfactant chemical potential, which is extracted
      from the set of adsorption isotherms each with a fixed slit width. When the slit
      width approaches the thickness of the two surfactant layers, a first-order phase
      transition takes place, which is driven by the unfavorable hydrophobic-water
      contacts. At the transition, the average orientation of the surfactants switches
      from a high concentration of tails at the surface to a bilayer configuration
      where tail profiles from both sides merge in the center. The headgroups are
      pulled slightly away from the surface. The interaction force jumps from a weak
      electrostatic repulsion at large distances (two effectively positively charged
      surface layers repel each other) to a strong electrostatic attraction at short
      distances (the central surfactant bilayer is attracted to the oppositely charged
      surfaces). The amount of adsorbed surfactants tend to decrease with decreasing
      distance between the surfaces but suddenly increases at the transition. Because
      of this, we anticipate that in surface force experiments, for example, there is a
      hysteresis associated with this transition: the forces and also the adsorbed
      amounts depend not only on the distance between the surfaces but also on the
      history if nonsufficient equilibration times are implemented.

PMID- 16285840
TI  - Depression in children and adolescents.
AB  - During the past 20 years, depression has been recognized widely in children and
      adolescents. However, even with what is known today about depression, many
      children and adolescents remain undiagnosed. Early recognition is imperative to
      prevent further episodes that may continue into adulthood. Depression in children
      and adolescents affects social development, academic performance, and ultimately,
      success as an adult. This article describes risk factors for depression,
      diagnostic criteria, medications, psychosocial interventions, and implications
      for school nursing practice.

PMID- 16285839
TI  - Local literature bias in genetic epidemiology: an empirical evaluation of the
      Chinese literature.
AB  - BACKGROUND: Postulated epidemiological associations are subject to several
      biases. We evaluated whether the Chinese literature on human genome epidemiology
      may offer insights on the operation of selective reporting and language biases.
      METHODS AND FINDINGS: We targeted 13 gene-disease associations, each already
      assessed by meta-analyses, including at least 15 non-Chinese studies. We searched
      the Chinese Journal Full-Text Database for additional Chinese studies on the same
      topics. We identified 161 Chinese studies on 12 of these gene-disease
      associations; only 20 were PubMed-indexed (seven English full-text). Many studies
      (14-35 per topic) were available for six topics, covering diseases common in
      China. With one exception, the first Chinese study appeared with a time lag (2-21
      y) after the first non-Chinese study on the topic. Chinese studies showed
      significantly more prominent genetic effects than non-Chinese studies, and 48%
      were statistically significant per se, despite their smaller sample size (median
      sample size 146 versus 268, p < 0.001). The largest genetic effects were often
      seen in PubMed-indexed Chinese studies (65% statistically significant per se).
      Non-Chinese studies of Asian-descent populations (27% significant per se) also
      tended to show somewhat more prominent genetic effects than studies of non-Asian
      descent (17% significant per se). CONCLUSION: Our data provide evidence for the
      interplay of selective reporting and language biases in human genome
      epidemiology. These biases may not be limited to the Chinese literature and point
      to the need for a global, transparent, comprehensive outlook in molecular
      population genetics and epidemiologic studies in general.

PMID- 16285841
TI  - The use of antidepressants in school-age children.
AB  - Approximately 5% of the pediatric population suffers from depression. Children
      suffering from depression should be treated first with some type of
      psychotherapy, cognitive therapy, and/or education. Pharmacotherapy (medications)
      should be used only as a last resort for those children suffering from severe,
      chronic, or recurring depression. The only antidepressant approved by the U.S.
      Food and Drug Administration for the treatment of depression in children is
      fluoxetine (Prozac), a selective serotonin reuptake inhibitor. In the school
      setting, children should be monitored closely upon the initiation of
      antidepressant therapy and changes in dosing or medication. They also should be
      monitored for side effects of the medication, response to therapy, and new signs
      of depression or worsening symptoms. After starting an antidepressant, children
      must be monitored closely for any changes in behavior, especially increased
      preoccupation with suicide. Any changes should be reported to the physician
      immediately for follow-up.

PMID- 16285842
TI  - The use of ergogenic agents in high school athletes.
AB  - Statistics reporting adolescent use of ergogenic agents are staggering. According
      to the Centers for Disease Control and Prevention Youth Risk Behavior
      Surveillance, 6.1% of students from grades 9 through 12 had taken illegal
      anabolic steroids without a prescription one or more times during their lifetime.
      Additionally, more adolescent athletes are using non-Food and Drug Administration
      regulated herbal supplements that claim ergogenic benefits. Many athletes either
      are unaware of or do not consider the possible health risks caused by these
      agents. School-based programs for athletes may be successful in preventing the
      use of ergogenic agents by increasing knowledge about such agents and offering
      skills in critical thinking to improve decision-making skills.

PMID- 16285843
TI  - Use of the preparticipation physical exam in screening for the female athlete
      triad among high school athletes.
AB  - The female athlete triad comprises 3 individual but interrelated conditions
      associated with athletic training: disordered eating, amenorrhea, and
      osteoporosis. Each condition is of medical concern, but when found within the
      triad, they can have serious medical consequences. The purpose of this study was
      to evaluate the effectiveness of preparticipation history and physical forms in
      high school athletic programs to screen for the triad, and to determine the
      prevalence of educational programs related to the female athlete triad. Results
      suggest that a majority of high school athletic programs are not adequately
      screening girls for the components of the triad, and schools lack educational
      programs targeting athletes and coaches. School nurses have the potential to play
      a vital role in the prevention and early identification of the triad through a
      preparticipation physical exam that specifically screens female athletes and in
      the implementation of educational programs for athletes and coaches regarding the
      disorders of the female athlete triad.

PMID- 16285844
TI  - Teachers' knowledge of normal and abnormal elimination patterns in elementary
      school children.
AB  - Dysfunctional elimination may be learned, to some degree. Because children spend
      nearly half of their waking hours at school, there is the potential for school to
      have a significant impact on their elimination patterns. Surveys were mailed to
      1,000 randomly selected Iowa public elementary school teachers; 467 of the
      surveys were returned. Findings indicate that most elementary school teachers are
      unaware of the potential health problems of elimination dysfunction. One third of
      respondents indicated that they ask children to wait to go to the bathroom.
      Suboptimal conditions exist in most of the school bathrooms, with only 35% of the
      boys' restrooms and 48% of the girls' restrooms reported as "always clean." Those
      teachers with more experience were more likely to report information about
      abnormal elimination to the school nurse. Very few teachers (18% of respondents)
      reported having received information about abnormal elimination and even fewer
      (8% of respondents) were aware of specialists trained to treat children with
      these problems. School nurses can have a significant impact on the development of
      healthy bladder habits in children. Teachers need information about normal and
      abnormal elimination patterns in children.

PMID- 16285845
TI  - Comparing the number of ill or injured students who are released early from
      school by school nursing and nonnursing personnel.
AB  - There is a growing demand for research linking specific educational services with
      positive student outcomes. Little empirical evidence exists to show that school
      nursing services improve student success. School attendance is one of many
      factors that has been associated with improved learning; school nurses can affect
      that factor. This study compared the number of students in a Midwest urban public
      school district who were dismissed from school early for illness or injury with
      and without interaction with a school nurse. A student sign-out and sign-in log
      identified the number of students who left school prior to the official dismissal
      time, and a school nurse activity log indicated the students who were dismissed
      early from school after contact with a school nurse. Analysis of these data
      indicates that 57% fewer students left school early with school nurse contact
      compared with those who left school early without such contact. The results of
      this study indicate school nurses may positively influence student school success
      by reducing avoidable early release from school for ill or injured students.

PMID- 16285849
TI  - John Maynard Smith.
AB  - John Maynard Smith was one of the most original thinkers in evolutionary biology
      of the post neo-Darwinian synthesis age. He was able to define new problems with
      clarity and by doing so open up new research directions. He did this in a number
      of areas including game theory and evolution, the evolution of sex, animal
      behavior, evolutionary transitions and molecular evolution. Although he is best
      known for his research and his ideas, he was a great expositor and wrote many
      books, including introductory texts in the areas of evolution and genetics,
      ecology and mathematical modeling, as well as advanced expositions of research
      problems.

PMID- 16285846
TI  - Medical family support needs and experiences in rural Queensland.
AB  - INTRODUCTION: Family issues have been recognised as major contributors to both
      rural GP retention in, and loss to, rural practice. This qualitative interview
      survey of rural medical spouses sought to identify and understand the support
      requirements and experiences that could be used to formulate strategies that may
      positively influence rural medical family retention. A concurrent key informant
      interview of 14 agencies associated with rural medical practitioner support
      sought information on those agencies' specific spouse/family support strategies.
      AIMS: The study's specific aims were to: investigate the experiences and needs of
      families in terms of support to settle and remain in rural and remote areas; and
      identify the range and type of formal and informal support strategies available
      to, and used by, rural medical families. METHODS: This was a qualitative study
      with two independent, but complementary, components: (1) in-depth, semi
      structured interviews with families of 15 purposively selected rural GPs; and (2)
      information provided by 14 support organisations. RESULTS AND DISCUSSION: Medical
      family support needs and experiences varied with time in a rural setting. The
      most frequently mentioned early difficulties included integrating into a
      community (9/15); childcare and schooling (8/15); being seen as the 'doctors
      spouse' (ie, loss of own identity) (7/15); and housing and housing maintenance
      (7/15). Support needs changed over time as respondents established their own
      support networks. Increasingly, support was required for timeout from the
      community (5/15), and to keep abreast of changing practice management
      requirements (4/15). Few formal support strategies were reported as known or used
      by spouses. Informal support strategies included partners of other GPs; hospital
      functions and informal social gatherings; clubs and organisations; local church
      groups, and friendships with other itinerants in the community. Spouses indicated
      important potential sources of support (both when new to community and later on)
      as a need for a 'head start' with local and regional networks (14/15); ability to
      talk to other spouses in similar situations (12/15); support for timeout or leave
      (12/15); access to a GP other than the GP spouse (10/15); information about
      childcare (9/15); practice and business management (8/15); and dealing with
      housing issues (6/15). Additionally, an orientation package was seen as a means
      of assisting new arrivals to get settled (12/15). The survey of
      agencies/organisations providing direct and indirect support revealed that there
      is little directly-funded family support in Queensland, although a number of
      bodies either have support activities in place or planned. The potential number
      of players presents a risk of duplication of effort unless there is effective
      inter-agency dialogue. CONCLUSIONS: Like their medical partners, spouses
      appreciate and value peer support and understanding. Strategies aimed at rural GP
      retention should consider the rural medical family as a unit for support
      purposes. Support organisations and rural communities must recognise and cater
      for changing support needs over time. The agency interviews provided some hope
      for the future, although funding for support activities appears to be limited.
      Perhaps of greater concern is the possibility for duplication of effort and
      activity, particularly in some areas, and potentially at the risk of ignoring
      others.

PMID- 16285850
TI  - The genetics of hearing and balance in zebrafish.
AB  - The zebrafish is an excellent model system for studying the molecular basis of
      inner ear development and function. The eggs develop ex utero and the ear is
      transparent for the first few weeks of life. Forward genetic screens and
      antisense technology have helped to elucidate the signaling pathways and
      molecules required for inner ear development and function. This review addresses
      the most recent advances in our understanding of how the ear forms and discusses
      the molecules in hair cells that are essential for sensing sound and movement in
      the zebrafish.

PMID- 16285851
TI  - Immunoglobulin gene diversification.
AB  - Three processes alter genomic sequence and structure at the immunoglobulin genes
      of B lymphocytes: gene conversion, somatic hypermutation, and class switch
      recombination. Though the molecular signatures of these processes differ, they
      occur by a shared pathway which is induced by targeted DNA deamination by a B
      cell-specific factor, activation induced cytidine deaminase (AID). Ubiquitous
      factors critical for DNA repair carry out all downstream steps, creating
      mutations and deletions in genomic DNA. This review focuses on the genetic and
      biochemical mechanisms of diversification of immunoglobulin genes.

PMID- 16285853
TI  - Cell-cycle control of gene expression in budding and fission yeast.
AB  - Cell-cycle control of transcription seems to be a universal feature of
      proliferating cells, although relatively little is known about its biological
      significance and conservation between organisms. The two distantly related yeasts
      Saccharomyces cerevisiae and Schizosaccharomyces pombe have provided valuable
      complementary insight into the regulation of periodic transcription as a function
      of the cell cycle. More recently, genome-wide studies of proliferating cells have
      identified hundreds of periodically expressed genes and underlying mechanisms of
      transcriptional control. This review discusses the regulation of three major
      transcriptional waves, which roughly coincide with three main cell-cycle
      transitions (initiation of DNA replication, entry into mitosis, and exit from
      mitosis). I also compare and contrast the transcriptional regulatory networks
      between the two yeasts and discuss the evolutionary conservation and possible
      roles for cell cycle-regulated transcription.

PMID- 16285852
TI  - Complexity in regulation of tryptophan biosynthesis in Bacillus subtilis.
AB  - Bacillus subtilis uses novel regulatory mechanisms in controlling expression of
      its genes of tryptophan synthesis and transport. These mechanisms respond to
      changes in the intracellular concentrations of free tryptophan and uncharged
      tRNA(Trp). The major B. subtilis protein that regulates tryptophan biosynthesis
      is the tryptophan-activated RNA-binding attenuation protein, TRAP. TRAP is a ring
      shaped molecule composed of 11 identical subunits. Active TRAP binds to unique
      RNA segments containing multiple trinucleotide (NAG) repeats. Binding regulates
      both transcription termination and translation in the trp operon, and translation
      of other coding regions relevant to tryptophan metabolism. When there is a
      deficiency of charged tRNA(Trp), B. subtilis forms an anti-TRAP protein, AT. AT
      antagonizes TRAP function, thereby increasing expression of all the genes
      regulated by TRAP. Thus B. subtilis and Escherichia coli respond to identical
      regulatory signals, tryptophan and uncharged tRNA(Trp), yet they employ different
      mechanisms in regulating trp gene expression.

PMID- 16285854
TI  - Comparative developmental genetics and the evolution of arthropod body plans.
AB  - The arthropods display a wide range of morphological diversity, varying tagmosis,
      as well as other aspects of the body plan, such as appendage and cuticular
      morphology. Here we review the roles of developmental regulatory genes in the
      evolution of arthropod morphology, with an emphasis on what is known from
      morphologically diverse species. Examination of tagmatic evolution reveals that
      these changes have been accompanied by changes in the expression patterns of Hox
      genes. In contrast, review of the modifications to wing morphology seen in
      insects shows that these body plan changes have generally favored alterations in
      downstream target genes. These and other examples are used to discuss the
      evolutionary implications of comparative developmental genetic data.

PMID- 16285856
TI  - Drosophila as a model for human neurodegenerative disease.
AB  - Among many achievements in the neurodegeneration field in the past decade, two
      require special attention due to the huge impact on our understanding of
      molecular and cellular pathogenesis of human neurodegenerative diseases. First is
      defining specific mutations in familial neurodegenerative diseases and second is
      modeling these diseases in easily manipulable model organisms including the fruit
      fly, nematode, and yeast. The power of these genetic systems has revealed many
      genetic factors involved in the various pathways affected, as well as provided
      potential drug targets for therapeutics. This review focuses on fruit fly models
      of human neurodegenerative diseases, with emphasis on how fly models have
      provided new insights into various aspects of human diseases.

PMID- 16285855
TI  - Concerted and birth-and-death evolution of multigene families.
AB  - Until around 1990, most multigene families were thought to be subject to
      concerted evolution, in which all member genes of a family evolve as a unit in
      concert. However, phylogenetic analysis of MHC and other immune system genes
      showed a quite different evolutionary pattern, and a new model called birth-and
      death evolution was proposed. In this model, new genes are created by gene
      duplication and some duplicate genes stay in the genome for a long time, whereas
      others are inactivated or deleted from the genome. Later investigations have
      shown that most non-rRNA genes including highly conserved histone or ubiquitin
      genes are subject to this type of evolution. However, the controversy over the
      two models is still continuing because the distinction between the two models
      becomes difficult when sequence differences are small. Unlike concerted
      evolution, the model of birth-and-death evolution can give some insights into the
      origins of new genetic systems or new phenotypic characters.

PMID- 16285857
TI  - Molecular mechanisms of germline stem cell regulation.
AB  - Germline stem cells (GSCs), which can self-renew and generate differentiated
      progeny, are unique stem cells in that they are solely dedicated to reproduction
      and transmit genetic information from generation to generation. Through the use
      of genetic techniques in Drosophila, Caenorhabditis elegans, and mouse, exciting
      progress has been made in understanding molecular mechanisms underlying
      interactions between stem cells and niches. The knowledge gained from studying
      GSCs has provided an intellectual framework for defining niches and molecular
      regulatory mechanisms for other adult stem cells. In this review, we summarize
      recent progress and discuss conserved mechanisms underlying GSC self-renewal and
      differentiation by comparing three GSC systems. Because GSCs and other adult stem
      cells share "stemness," we hope this review will help define fundamental
      principles of stem cell regulation and provide further guidance for future
      studies of other adult stem cells.

PMID- 16285858
TI  - Molecular signatures of natural selection.
AB  - There is an increasing interest in detecting genes, or genomic regions, that have
      been targeted by natural selection. The interest stems from a basic desire to
      learn more about evolutionary processes in humans and other organisms, and from
      the realization that inferences regarding selection may provide important
      functional information. This review provides a nonmathematical description of the
      issues involved in detecting selection from DNA sequences and SNP data and is
      intended for readers who are not familiar with population genetic theory.
      Particular attention is placed on issues relating to the analysis of large-scale
      genomic data sets.

PMID- 16285859
TI  - T-box genes in vertebrate development.
AB  - The myriad developmental roles served by the T-box family of transcription factor
      genes defy easy categorization. Present in all metazoans, the T-box genes are
      involved in early embryonic cell fate decisions, regulation of the development of
      extraembryonic structures, embryonic patterning, and many aspects of
      organogenesis. They are unusual in displaying dosage sensitivity in most
      instances. In humans, mutations in T-box genes are responsible for developmental
      dysmorphic syndromes, and several T-box genes have been implicated in neoplastic
      processes. T-box transcription factors function in many different signaling
      pathways, notably bone morphogenetic protein and fibroblast growth factor
      pathways. The few downstream target genes that have been identified indicate a
      wide range of downstream effectors.

PMID- 16285861
TI  - Evolutionary genetics of reproductive behavior in Drosophila: connecting the
      dots.
AB  - Species of the genus Drosophila exhibit enormous variation in all of their
      reproductive behaviors: resource use and specialization, courtship signaling,
      sperm utilization, and female remating. The genetic bases of this variability and
      its evolution are poorly understood. At the same time, Drosophila comparative
      genomics now has developed to a point at which approaches previously only
      possible with D. melanogaster can be exploited to address these questions. We
      have taken advantage of the known phylogenetic relationships of this group of
      flies not only to place these behaviors in an evolutionary framework, but to
      provide a roadmap for future genetic studies.

PMID- 16285862
TI  - Sex determination in the teleost medaka, Oryzias latipes.
AB  - Although the sex of most animals is determined by genetic information, sex
      determining genes had been identified only in mammals, several flies, and the
      worm Caenorhabditis elegans until the recent discovery of DMY (DM-domain gene on
      the Y chromosome) in the sex-determining region on the Y chromosome of the
      teleost fish medaka, Oryzias latipes. Functional and expression analyses of DMY
      have shown it to be the master gene for male sex determination in the medaka. The
      only sex-determining genes found so far in vertebrates are Sry and DMY.
      Therefore, the medaka is expected to become a good experimental animal for
      investigating the precise mechanisms involved in primary sex determination in
      nonmammalian vertebrates. This article reviews the origin of DMY and the sexual
      development of gonads in the medaka. The putative functions of DMY are also
      discussed.

PMID- 16285863
TI  - Orthologs, paralogs, and evolutionary genomics.
AB  - Orthologs and paralogs are two fundamentally different types of homologous genes
      that evolved, respectively, by vertical descent from a single ancestral gene and
      by duplication. Orthology and paralogy are key concepts of evolutionary genomics.
      A clear distinction between orthologs and paralogs is critical for the
      construction of a robust evolutionary classification of genes and reliable
      functional annotation of newly sequenced genomes. Genome comparisons show that
      orthologous relationships with genes from taxonomically distant species can be
      established for the majority of the genes from each sequenced genome. This review
      examines in depth the definitions and subtypes of orthologs and paralogs,
      outlines the principal methodological approaches employed for identification of
      orthology and paralogy, and considers evolutionary and functional implications of
      these concepts.

PMID- 16285864
TI  - The moss Physcomitrella patens.
AB  - The moss Physcomitrella patens, like seed plants, shows alternation of
      generations, but its gametophyte, the haploid phase of the life cycle, is
      dominant, making it ideal for genetic studies. Crosses show direct segregations,
      so F2 or test crosses are unnecessary. Mutagenesis yields mutants, the phenotype
      of which is directly evident. Haploid tissue can be propagated vegetatively,
      allowing the maintenance of mutants blocked early in development. Protoplasts,
      isolated from filamentous gametophytic tissue, regenerate directly into
      filamentous tissue, providing an abundant supply of single haploid cells for
      transformation. Recombination occurs at a high frequency between genomic
      sequences in transforming DNA and the corresponding chromosomal sequences,
      allowing precise inactivation or modification of genes. RNAi technology allows
      the inactivation of the expression of gene families and the partial knockdown of
      essential genes. Over 100,000 ESTs have been sequenced and annotated, and
      sequencing of the genome should be completed by the end of 2005.

PMID- 16285866
TI  - Switches in bacteriophage lambda development.
AB  - The lysis-lysogeny decision of bacteriophage lambda (lambda) is a paradigm for
      developmental genetic networks. There are three key features, which characterize
      the network. First, after infection of the host bacterium, a decision between
      lytic or lysogenic development is made that is dependent upon environmental
      signals and the number of infecting phages per cell. Second, the lysogenic
      prophage state is very stable. Third, the prophage enters lytic development in
      response to DNA-damaging agents. The CI and Cro regulators define the lysogenic
      and lytic states, respectively, as a bistable genetic switch. Whereas CI
      maintains a stable lysogenic state, recent studies indicate that Cro sets the
      lytic course not by directly blocking CI expression but indirectly by lowering
      levels of CII which activates cI transcription. We discuss how a relatively
      simple phage like lambda employs a complex genetic network in decision-making
      processes, providing a challenge for theoretical modeling.

PMID- 16285867
TI  - Nonhomologous end joining in yeast.
AB  - Nonhomologous end joining (NHEJ), the direct rejoining of DNA double-strand
      breaks, is closely associated with illegitimate recombination and chromosomal
      rearrangement. This has led to the concept that NHEJ is error prone. Studies with
      the yeast Saccharomyces cerevisiae have revealed that this model eukaryote has a
      classical NHEJ pathway dependent on Ku and DNA ligase IV, as well as alternative
      mechanisms for break rejoining. The evolutionary conservation of the Ku-dependent
      process includes several genes dedicated to this pathway, indicating that
      classical NHEJ at least is a strong contributor to fitness in the wild. Here we
      review how double-strand break structure, the yeast NHEJ proteins, and
      alternative rejoining mechanisms influence the accuracy of break repair. We also
      consider how the balance between NHEJ and homologous repair is regulated by cell
      state to promote genome preservation. The principles discussed are instructive to
      NHEJ in all organisms.

PMID- 16285868
TI  - Plasmid segregation mechanisms.
AB  - Bacterial plasmids encode partitioning (par) loci that ensure ordered plasmid
      segregation prior to cell division. par loci come in two types: those that encode
      actin-like ATPases and those that encode deviant Walker-type ATPases. ParM, the
      actin-like ATPase of plasmid R1, forms dynamic filaments that segregate plasmids
      paired at mid-cell to daughter cells. Like microtubules, ParM filaments exhibit
      dynamic instability (i.e., catastrophic decay) whose regulation is an important
      component of the DNA segregation process. The Walker box ParA ATPases are related
      to MinD and form highly dynamic, oscillating filaments that are required for the
      subcellular movement and positioning of plasmids. The role of the observed ATPase
      oscillation is not yet understood. However, we propose a simple model that
      couples plasmid segregation to ParA oscillation. The model is consistent with the
      observed movement and localization patterns of plasmid foci and does not require
      the involvement of plasmid-specific host-encoded factors.

PMID- 16285865
TI  - A mitochondrial paradigm of metabolic and degenerative diseases, aging, and
      cancer: a dawn for evolutionary medicine.
AB  - Life is the interplay between structure and energy, yet the role of energy
      deficiency in human disease has been poorly explored by modern medicine. Since
      the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary
      calories into usable energy, generating reactive oxygen species (ROS) as a toxic
      by-product, I hypothesize that mitochondrial dysfunction plays a central role in
      a wide range of age-related disorders and various forms of cancer. Because
      mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes
      essential genes for energy production, I propose that the delayed-onset and
      progressive course of the age-related diseases results from the accumulation of
      somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific
      manifestations of these diseases may result from the varying energetic roles and
      needs of the different tissues. The variation in the individual and regional
      predisposition to degenerative diseases and cancer may result from the
      interaction of modern dietary caloric intake and ancient mitochondrial genetic
      polymorphisms. Therefore the mitochondria provide a direct link between our
      environment and our genes and the mtDNA variants that permitted our forbears to
      energetically adapt to their ancestral homes are influencing our health today.

PMID- 16285869
TI  - Use of the zebrafish system to study primitive and definitive hematopoiesis.
AB  - The zebrafish (Danio rerio) has emerged as an ideal organism for the study of
      hematopoiesis, the process by which all the cellular elements of the blood are
      formed. These elements, including erythrocytes, granulocytes, monocytes,
      lymphocytes, and thrombocytes, are formed through complex genetic signaling
      pathways that are highly conserved throughout phylogeny. Large-scale forward
      genetic screens have identified numerous blood mutants in zebrafish, helping to
      elucidate specific signaling pathways important for hematopoietic stem cells
      (HSCs) and the various committed blood cell lineages. Here we review both
      primitive and definitive hematopoiesis in zebrafish, discuss various genetic
      methods available in the zebrafish model for studying hematopoiesis, and describe
      some of the zebrafish blood mutants identified to date, many of which have known
      human disease counterparts.

PMID- 16285870
TI  - Mitochondrial morphology and dynamics in yeast and multicellular eukaryotes.
AB  - Mitochondria form dynamic tubular networks that continually change their shape
      and move throughout the cell. In eukaryotes, these organellar gymnastics are
      controlled by numerous pathways that preserve proper mitochondrial morphology and
      function. The best understood of these are the fusion and fission pathways, which
      rely on conserved GTPases and their binding partners to regulate organelle
      connectivity and copy number in healthy cells and during apoptosis. In budding
      yeast, mitochondrial shape is also maintained by proteins acting in the
      tubulation pathway. Novel proteins and pathways that control mitochondrial
      dynamics continue to be discovered, indicating that the mechanisms governing this
      organelle's behavior are more sophisticated than previously appreciated. Here we
      review recent advances in the field of mitochondrial dynamics and highlight the
      importance of these pathways to human health.

PMID- 16285871
TI  - RNA-guided DNA deletion in Tetrahymena: an RNAi-based mechanism for programmed
      genome rearrangements.
AB  - Ciliated protozoan are unicellular eukaryotes. Most species in this diverse group
      display nuclear dualism, a special feature that supports both somatic and
      germline nuclei in the same cell. Probably due to this unique life style, they
      exhibit unusual nuclear characteristics that have intrigued researchers for
      decades. Among them are large-scale DNA rearrangements, which restructure the
      somatic genome to become drastically different from its germline origin. They
      resemble the classical phenomenon of chromatin diminution in some nematodes
      discovered more than a century ago. The mechanisms of such rearrangements, their
      biological roles, and their evolutionary origins have been difficult to
      understand. Recent studies have revealed a clear link to RNA interference, and
      begin to shed light on these issues. Using the simple ciliate Tetrahymena as a
      model, this chapter summarizes the physical characterization of these processes,
      describes recent findings that connect them to RNA interference, and discusses
      the details of their mechanisms, potential roles in genome defense, and possible
      occurrences in other organisms.

PMID- 16285872
TI  - Molecular genetics of axis formation in zebrafish.
AB  - The basic vertebrate body plan of the zebrafish embryo is established in the
      first 10 hours of development. This period is characterized by the formation of
      the anterior-posterior and dorsal-ventral axes, the development of the three germ
      layers, the specification of organ progenitors, and the complex morphogenetic
      movements of cells. During the past 10 years a combination of genetic,
      embryological, and molecular analyses has provided detailed insights into the
      mechanisms underlying this process. Maternal determinants control the expression
      of transcription factors and the location of signaling centers that pattern the
      blastula and gastrula. Bmp, Nodal, FGF, canonical Wnt, and retinoic acid signals
      generate positional information that leads to the restricted expression of
      transcription factors that control cell type specification. Noncanonical Wnt
      signaling is required for the morphogenetic movements during gastrulation. We
      review how the coordinated interplay of these molecules determines the fate and
      movement of embryonic cells.

PMID- 16285873
TI  - Chromatin remodeling in dosage compensation.
AB  - In many multicellular organisms, males have one X chromosome and females have
      two. Dosage compensation refers to a regulatory mechanism that insures the
      equalization of X-linked gene products in males and females. The mechanism has
      been studied at the molecular level in model organisms belonging to three
      distantly related taxa; in these organisms, equalization is achieved by shutting
      down one of the two X chromosomes in the somatic cells of females, by decreasing
      the level of transcription of the two doses of X-linked genes in females relative
      to males, or by increasing the level of transcription of the single dose of X
      linked genes in males. The study of dosage compensation in these different forms
      has revealed the existence of an amazing number of interacting chromatin
      remodeling mechanisms that affect the function of entire chromosomes.

PMID- 16285874
TI  - Gene therapy in urology: strategies to translate theory into practice.

PMID- 16285875
TI  - The management of superficial transitional cell carcinoma of the bladder: a
      critical assessment of contemporary concepts and future perspectives.

PMID- 16285876
TI  - Complementary and alternative medicine in urology.
AB  - Complementary and alternative medicine (CAM) includes various practices, measures
      and products which are not presently considered to be a part of conventional
      (mainstream) medicine. Herbal products, vitamins, minerals and amino acids are
      increasingly popular as dietary supplements for the treatment, improvement and
      prophylaxis of urological diseases, and to improve general health and well-being.
      As these products are freely available without prescription, conventional
      healthcare providers are often unaware that their patients are using CAM. It is
      essential to know that some herbal supplements may act in the same way as
      chemical drugs, and that they originate 'from nature' does not mean that they are
      safe and/or with no potential harmful effects and/or toxicity. Eventual
      interactions with conventional medications and contamination with prescription
      drugs and metals have been reported. The active components of many
      phytotherapeutic preparations and their mechanism(s) of action are still being
      determined and evaluated. There is scientific evidence for the effectiveness of
      some CAM treatments, but for most there are important key questions yet to be
      answered through basic research and well-designed studies according to
      established guidelines. Because of the increasing popularity and use of CAM,
      conventional healthcare providers, including urologists, should not ignore it,
      and be well informed about the benefits and potential risks of dietary
      supplements, so that they can advise their patients about this developing field.
      Whenever necessary and possible, lifestyle and behavioural changes should be
      recommended before using CAM, and eventually be supplemented by CAM as a second
      step.

PMID- 16285877
TI  - Internet resources for urologists.

PMID- 16285879
TI  - A case control study on psychiatric disorders in Hashimoto disease and Euthyroid
      Goitre: not only depressive but also anxiety disorders are associated with
      thyroid autoimmunity.
AB  - OBJECTIVE: To evaluate the association between mood and anxiety disorders in
      Hashimoto disease and Euthyroid Goitre in a case control study. METHODS: Cases
      included 19 subjects with Hashimoto disease in euthyroid phase, 19 subjects with
      euthyroid goitre, 2 control groups each of 76 subjects matched (4/1) according to
      age and sex drawn from the data base of a community based sample. Psychiatric
      diagnoses were formulated using the International Composite Diagnostic Interview
      Simplified, according to DSM-IV criteria. All subjects underwent a complete
      thyroid evaluation including physical examination, thyroid echography and measure
      of serum free T4 (FT4), free T3 (FT3), thyroid-stimulating hormone (TSH) and anti
      thyroid peroxidase autoantibodies (anti-TPO). RESULTS: Subjects with Hashimoto
      disease showed higher frequencies of lifetime Depressive Episode (OR = 6.6, C.L.
      95% 1.2-25.7), Generalized Anxiety Disorders (OR = 4,9 Cl 95% 1.5-25.4) and
      Social Phobia (OR = 20.0, CL 95% 2.3-153.3) whilst no differences were found
      between subjects with goitre and controls. CONCLUSION: The study seems to confirm
      that risk for depressive disorders in subjects with thyroiditis is independent of
      the thyroid function detected by routine tests and indicates that not only mood
      but also anxiety disorders may be associated with Hashimoto disease.

PMID- 16285880
TI  - Predicting the risk of falling--efficacy of a risk assessment tool compared to
      nurses' judgement: a cluster-randomised controlled trial [ISRCTN37794278].
AB  - BACKGROUND: Older people living in nursing homes are at high risk of falling
      because of their general frailty and multiple pathologies. Prediction of falls
      might lead to an efficient allocation of preventive measures. Although several
      tools to assess the risk of falling have been developed, their impact on
      clinically relevant endpoints has never been investigated. The present study will
      evaluate the clinical efficacy and consequences of different fall risk assessment
      strategies. STUDY DESIGN: Cluster-randomised controlled trial with nursing home
      clusters randomised either to the use of a standard fall risk assessment tool
      alongside nurses' clinical judgement or to nurses' clinical judgement alone.
      Standard care of all clusters will be optimised by structured education on best
      evidence strategies to prevent falls and fall related injuries. 54 nursing home
      clusters including 1,080 residents will be recruited. Residents must be > or = 70
      years, not bedridden, and living in the nursing home for more than three months.
      The primary endpoint is the number of participants with at least one fall at 12
      months. Secondary outcome measures are the number of falls, clinical consequences
      including side effects of the two risk assessment strategies. Other measures are
      fall related injuries, hospital admissions and consultations with a physician,
      and costs.

PMID- 16285881
TI  - Studies of the intermediary metabolism in cultured cells of the insect Spodoptera
      frugiperda using 13C- or 15N-labelled tracers.
AB  - BACKGROUND: Insect cells can serve as host systems for the recombinant expression
      of eukaryotic proteins. Using this platform, the controlled expression of 15N/13C
      labelled proteins requires the analysis of incorporation paths and rates of
      isotope-labelled precursors present in the medium into amino acids. For this
      purpose, Spodoptera frugiperda cells were grown in a complex medium containing [U
      13C6]glucose. In a second experiment, cultures of S. frugiperda were grown in the
      presence of 15N-phenylalanine. RESULTS: Quantitative NMR analysis showed
      incorporation of the proffered [U-13C6]glucose into the ribose moiety of
      ribonucleosides (40 - 45%) and into the amino acids, alanine (41%), glutamic
      acid/glutamine (C-4 and C-5, 30%) and aspartate/asparagine (15%). Other amino
      acids and the purine ring of nucleosides were not formed from exogenous glucose
      in significant amounts (> 5%). Prior to the incorporation into protein the
      proffered 15N-phenylalanine lost about 70% of its label by transamination and the
      labelled compound was not converted into tyrosine to a significant extent.
      CONCLUSION: Growth of S. frugiperda cells in the presence of [U-13C6]glucose is
      conducive to the fractional labelling of ribonucleosides, alanine, glutamic
      acid/glutamine and aspartic acid/asparagine. The isotopolog compositions of the
      ribonucleosides and of alanine indicate considerable recycling of carbohydrate
      intermediates in the reductive branch of the pentose phosphate pathway. The
      incorporation of 15N-labelled amino acids may be hampered by loss of the 15N
      label by transamination.

PMID- 16285882
TI  - Increase of mitochondrial DNA content and transcripts in early bovine
      embryogenesis associated with upregulation of mtTFA and NRF1 transcription
      factors.
AB  - BACKGROUND: Recent work has shown that mitochondrial biogenesis and mitochondrial
      functions are critical determinants of embryonic development. However, the
      expression of the factors controlling mitochondrial biogenesis in early
      embryogenesis has received little attention so far. METHODS: We used real-time
      quantitative PCR to quantify mitochondrial DNA (mtDNA) in bovine oocytes and in
      various stages of in vitro produced embryos. To investigate the molecular
      mechanisms responsible for the replication and the transcriptional activation of
      mtDNA, we quantified the mRNA corresponding to the mtDNA-encoded cytochrome
      oxidase 1 (COX1), and two nuclear-encoded factors, i.e. the Nuclear Respiratory
      Factor 1 (NRF1), and the nuclear-encoded Mitochondrial Transcription Factor A
      (mtTFA). RESULTS: Unlike findings reported in mouse embryos, the mtDNA content
      was not constant during early bovine embryogenesis. We found a sharp, 60%
      decrease in mtDNA content between the 2-cell and the 4/8-cell stages. COX1 mRNA
      was constant until the morula stage after which it increased dramatically. mtTFA
      mRNA was undetectable in oocytes and remained so until the 8/16-cell stage; it
      began to appear only at the morula stage, suggesting de novo synthesis. In
      contrast, NRF1 mRNA was detectable in oocytes and the quantity remained constant
      until the morula stage. CONCLUSION: Our results revealed a reduction of mtDNA
      content in early bovine embryos suggesting an active process of mitochondrial DNA
      degradation. In addition, de novo mtTFA expression associated with mitochondrial
      biogenesis activation and high levels of NRF1 mRNA from the oocyte stage onwards
      argue for the essential function of these factors during the first steps of
      bovine embryogenesis.

PMID- 16285883
TI  - Serum concentration of selenium in healthy individuals living in Tehran.
AB  - OBJECTIVE: To investigate whether daily diet provides adequate selenium intake in
      healthy men and women living in Tehran, Iran. METHOD: Serum level of selenium was
      determined in 184 healthy individuals of both genders. The samples were divided
      into two age groups, adults and children, for analysis. The serum level of
      selenium was determined using hydride generation and flame atomic absorption
      spectroscopy. RESULTS: The mean and standard deviation of serum selenium levels
      in children (1-16 years) was 84.3 +/- 11 microg/l and there was no significant
      difference between genders in this group. In adults (older than 16 years) the
      mean serum selenium level was 100.6 +/- 13 SD microg/l; among women the mean was
      93.9 +/- 14 SD microg/l and among men it was 102.2 +/- 12 SD microg/l. The mean
      selenium level in men was higher than in women and data analysis showed a
      significant difference between them (p < 0.005). There was also a positive
      correlation between higher selenium serum concentration and age in men (P <
      0.001). Daily intake of selenium in men and women was calculated to be 67 microg
      and 62.1 microg respectively. CONCLUSION: Our results show that the serum
      concentration of selenium in an Iranian population is similar to other
      nationalities in the Middle East, particularly Saudi Arabia.

PMID- 16285884
TI  - The Visual Analog rating Scale of health-related quality of life: an examination
      of end-digit preferences.
AB  - BACKGROUND: The Visual Analog Scale (VAS) has been extensively used in the
      valuation of health-related quality of life (HRQL). The objective of this paper
      is to examine the measurement error (rounding) explanation for the higher
      prevalence of VAS scores ending with a zero, and to provide an alternative
      interpretation. METHODS: The analysis is based on more than 4,500 reported VAS
      valuations of own HRQL, included in two Israeli health surveys (1993 and 2000).
      Bivariate and logistic regression analyses are used. RESULTS: The results show
      that reporting VAS scores ending with a 0 (...-20, ..0,10,20.....) decreases and
      scores ending with a 5 (...-15,-5,5,15,25,...) and with any other integer (...
      12, -11,...1,2,...,92,..99) increases as VAS scores depart from 50, particularly
      when increasing up to 100. This pattern remains after controlling for personal
      characteristics determining the level of VAS. DISCUSSION: Rounding true HRQL to
      the nearest 10's or 5's cannot explain the specific pattern found. It is
      suggested that this pattern corresponds to a S-shaped value function, where
      individuals tend to evaluate their HRQL as "gains" or "losses" relative to a
      reference point evaluated at 50. This particular reference score originates from
      being a traditional "passing threshold" and the scale's midpoint. Several
      implications of this interpretation to the measurement of HRQL are discussed.

PMID- 16285885
TI  - Presence of a functional but dispensable nuclear export signal in the HTLV-2 Tax
      protein.
AB  - BACKGROUND: Human T-cell leukemia virus type 1 and type 2 are related human
      retroviruses. HTLV-1 is the etiological agent of the Adult T-cell
      Leukemia/Lymphoma and of the Tropical Spastic Paraparesis/HTLV-1 Associated
      Myelopathy, whereas, HTLV-2 infection has not been formally associated with any T
      cell malignancy. HTLV-1 and 2 genomes encode, respectively, the Tax1 and Tax2
      proteins whose role is to transactivate the viral promoter. HTLV-1 and HTLV-2 Tax
      sequences display 28% divergence at the amino acid level. Tax1 is a shuttling
      protein that possesses both a non canonical nuclear import (NLS) and a nuclear
      export (NES) signal. We have recently demonstrated that Tax1 and Tax2 display
      different subcellular localization and that residues 90-100 are critical for this
      process. We investigate in the present report, whether Tax2 also possesses a
      functional NES. RESULTS: We first used a NES prediction method to determine
      whether the Tax2 protein might contain a NES and the results do suggest the
      presence of a NES sequence in Tax2. Using Green Fluorescent Protein-NES (GFP-NES)
      fusion proteins, we demonstrate that the Tax2 sequence encompasses a functional
      NES (NES2). As shown by microscope imaging, NES2 is able to mediate translocation
      of GFP from the nucleus, without the context of a full length Tax protein.
      Furthermore, point mutations or leptomycin B treatment abrogate NES2 function.
      However, within the context of full length Tax2, similar point mutations in the
      NES2 leucine rich stretch do not modify Tax2 localization. Finally, we also show
      that Tax1 NES function is dependent upon the positioning of the nuclear export
      signal "vis-a-vis" GFP. CONCLUSION: HTLV-2 Tax NES is functional but dispensable
      for the protein localization in vitro.

PMID- 16285887
TI  - Colovaginal anastomosis: an unusual complication of stapler use in restorative
      procedure after Hartmann operation.
AB  - BACKGROUND: Rectovaginal fistula is uncommon after lower anterior resection for
      rectal cancer. The most leading cause of this complication is involvement of the
      posterior wall of the vagina into the staple line when firing the circular
      stapler. CASE PRESENTATION: A 50-year-old women underwent resection for
      obstructed carcinoma of the sigmoid colon with Hartmann procedure. Four months
      later she underwent restorative surgery with circular stapler. Following which
      she developed rectovaginal fistula. A transvaginal repair was performed but stool
      passing from vagina not per rectum. Laporotomy revealed colovaginal anastomosis,
      which was corrected accordingly. Patient had an uneventful recovery. CONCLUSION:
      Inadvertent formation of colovaginal anastomosis associated with a rectovaginal
      fistula is a rare complication caused by the operator's error. The present case
      again highlights the importance of ensuring that the posterior wall of vagina is
      away from the staple line.

PMID- 16285886
TI  - Membrane TNF confers protection to acute mycobacterial infection.
AB  - BACKGROUND: Tumour necrosis factor (TNF) is crucial for the control of
      mycobacterial infection as TNF deficient (KO) die rapidly of uncontrolled
      infection with necrotic pneumonia. Here we investigated the role of membrane TNF
      for host resistance in knock-in mice with a non-cleavable and regulated allele
      (mem-TNF). METHODS: C57BL/6, TNF KO and mem-TNF mice were infected with M.
      tuberculosis H37Rv (Mtb at 100 CFU by intranasal administration) and the
      survival, bacterial load, lung pathology and immunological parameters were
      investigated. Bone marrow and lymphocytes transfers were used to test the role of
      membrane TNF to confer resistance to TNF KO mice. RESULTS: While TNF-KO mice
      succumbed to infection within 4-5 weeks, mem-TNF mice recruited normally T cells
      and macrophages, developed mature granuloma in the lung and controlled acute Mtb
      infection. However, during the chronic phase of infection mem-TNF mice succumbed
      to disseminated infection with necrotic pneumonia at about 150 days.
      Reconstitution of irradiated TNF-KO mice with mem-TNF derived bone marrow cells,
      but not with lymphocytes, conferred host resistance to Mtb infection in TNF-KO
      mice. CONCLUSION: Membrane expressed TNF is sufficient to allow cell-cell
      signalling and control of acute Mtb infection. Bone marrow cells, but not
      lymphocytes from mem-TNF mice confer resistance to infection in TNF-KO mice. Long
      term infection control with chronic inflammation likely disrupting TNF mediated
      cell-cell signalling, additionally requires soluble TNF.

PMID- 16285890
TI  - T cell vaccination as an immunotherapy for autoimmune diseases.
AB  - Immunization with inactivated autoreactive T cells (T cell vaccination) selected
      from individual's own T cell repertoire provides a unique in vivo setting for
      testing immune regulation that is known to involve interactions of a variety of
      related surface molecules (1). It induces regulatory immune responses that
      closely resemble the in vivo situation where the immune system is challenged by
      clonal activation and expansion of given T cell populations in various autoimmune
      diseases. T cell vaccination provides a powerful means of eliciting natural
      reactions of the immune system in response to clonal expansion of T cells, which
      can be used as a therapeutic approach to suppress or eliminate specific
      pathogenic autoreactive T cells in autoimmune conditions. Clinical trials using T
      cell vaccination to deplete autoreactive T cells in human autoimmune conditions
      have begun to reveal the pathologic relevance of various autoimmune T cell
      populations in the disease processes, providing a unique opportunity to test the
      autoimmune theories in a clinical setting.

PMID- 16285888
TI  - A refined in vitro model to study inflammatory responses in organotypic membrane
      culture of postnatal rat hippocampal slices.
AB  - BACKGROUND: Propagated tissue degeneration, especially during aging, has been
      shown to be enhanced through potentiation of innate immune responses.
      Neurodegenerative diseases and a wide variety of inflammatory conditions are
      linked together and several anti-inflammatory compounds considered as having
      therapeutic potential for example in Alzheimer's disease (AD). In vitro brain
      slice techniques have been widely used to unravel the complexity of
      neuroinflammation, but rarely, has the power of the model itself been reported.
      Our aim was to gain a more detailed insight and understanding of the behaviour of
      hippocampus tissue slices in serum-free, interface culture per se and after
      exposure to different pro- and anti-inflammatory compounds. METHODS: The
      responses of the slices to pro- and anti-inflammatory stimuli were monitored at
      various time points by measuring the leakage of lactate dehydrogenase (LDH) and
      the release of cytokines interleukin 6 (IL-6) and tumour necrosis factor alpha
      (TNF-alpha) and nitric oxide (NO) from the culture media. Histological methods
      were applied to reveal the morphological status after exposure to stimuli and
      during the time course of the culture period. Statistical power analysis were
      made with nQuery Advisor, version 5.0, (Statistical Solutions, Saugus, MA)
      computer program for Wilcoxon (Mann-Whitney) rank-sum test. RESULTS: By using the
      interface membrane culture technique, the hippocampal slices largely recover from
      the trauma caused by cutting after 4-5 days in vitro. Furthermore, the cultures
      remain stable and retain their responsiveness to inflammatory stimuli for at
      least 3 weeks. During this time period, cultures are susceptible to modification
      by inflammatory stimuli as assessed by quantitative biochemical assays and
      morphological characterizations. CONCLUSION: The present report outlines the
      techniques for studying immune responses using a serum-free slice culture model.
      Statistically powerful data under controlled culture conditions and with
      ethically justified use of animals can be obtained as soon as after 4-5 DIV. The
      model is most probably suitable also for studies of chronic inflammation.

PMID- 16285889
TI  - Wavelength dependence of optical action potentials in the isolated rat atrium.
AB  - The wavelength dependence of optical action potentials was studied using voltage
      sensitive merocyanine-rhodanine, merocyanine-oxazolone, and oxonol dyes in the
      isolated rat atrium preparation. Most of the dyes had action spectra that were
      similar to those reported in other preparations. Species-to-species difference
      was observed with a merocyanine-oxazolone dye.

PMID- 16285891
TI  - The role and mechanisms of double negative regulatory T cells in the suppression
      of immune responses.
AB  - Accumulating evidence has demonstrated that regulatory T (Treg) cells play an
      important role in the maintenance of immunologic self-tolerance and in down
      regulating various immune responses. Thus, there has recently been an increasing
      interest in studying the biology of Treg cells as well as their potential
      application in treating immune diseases. Many types of Treg cell subsets have
      been reported in a variety of disease models. Among these subsets, alpha beta
      TCR(+)CD3(+)CD4(-)CD8(-) double negative (DN) Treg cells are defined by their
      capability of inhibiting immune responses via directly killing effector T cells
      in an antigen specific fashion. Furthermore, DN Treg cells have been shown to
      develop regulatory activity after encountering specific antigens, partially
      mediated by the acquisition of MHC-peptide complexes from antigen presenting
      cells (APCs). The presentation of acquired alloantigens on DN T cells allows for
      the specific interaction between DN Treg cells and alloantigen reactive effector
      T cells. Once the DN Treg and target cells have come into contact, killing is
      then mediated by Fas/Fas-ligand interactions, and perhaps through other
      unidentified pathways. Further characterization of the functions, molecular
      expression and mechanisms of activation of DN Treg cells will help in the
      development of novel therapies to induce antigen specific tolerance to self and
      foreign antigens.

PMID- 16285892
TI  - Chemokines and chemokine receptors as novel therapeutic targets in rheumatoid
      arthritis (RA): inhibitory effects of traditional Chinese medicinal components.
AB  - Chemokines belong to a large family of inflammatory cytokines responsible for
      migration and accumulation of leukocytes at inflammatory sites. Over the past
      decade, accumulating evidence indicated a crucial role for chemokines and
      chemokine receptors in the pathophysiology of rheumatoid arthritis (RA). RA is a
      chronic autoimmune disease in which the synovial tissue is heavily infiltrated by
      leukocytes. Chemokines play an important role in the infiltration, localization,
      retention of infiltrating leukocytes and generation of ectopic germinal centers
      in the inflamed synovium. Recent evidence also suggests that identification of
      inhibitors directly targeting chemokines or their receptors may provide a novel
      therapeutic strategy in RA. Traditional Chinese medicines (TCMs) have a long
      history in the treatment of inflammatory joint disease. The basis for the
      clinical benefits of TCM remains largely unclear. Our studies have led to the
      identification of numerous novel chemokine/chemokine receptor inhibitors present
      in anti-inflammatory TCMs. All of these inhibitors were previously reported by
      other researchers to have anti-arthritic effect, which may be attributable, at
      least in part, to their inhibitory effect on chemokine and/or chemokine receptor.
      Therefore, identification of agents capable of targeting chemokine/chemokine
      receptor interactions has suggested a mechanism of action for several TCM
      components and provided a means of identifying additional anti-RA TCM. Thus, this
      approach may lead to the discovery of new inhibitors of chemokines or chemokine
      receptors that can be used to treat diseases associated with inappropriately
      overactive chemokine mediated inflammatory reactions.

PMID- 16285893
TI  - NF-kappaB and its regulation on the immune system.
AB  - NF-kappaB is a transcription factor of eukaryote, whose family comprises five
      members in mammals and three in drosophila. Transcription factors of the NF
      kappaB family are activated in response to signals that lead to cell growth,
      differentiation, apoptosis and other events. NF-kappaB takes part in expression
      of numerous cytokines and adhesion molecules which are critical elements involved
      in the regulation of immune responses. In this review, we focus on our current
      understanding of NF-kappaB signal pathway and its role in the innate and adaptive
      immune responses in which these transcription factors have a key regulatory
      function. Furthermore we review what is currently known about their effects
      associated with apoptosis.

PMID- 16285894
TI  - Dendritic cells as vectors for immunotherapy of tumor and its application for
      gastric cancer therapy.
AB  - Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells
      (APCs) with the ability to stimulate naive resting T cells and initiate primary
      immune responses. DCs are poised to capture antigen (Ag), migrate to draining
      lymphoid organs, and, after a process of maturation, select Ag-specific
      lymphocytes to which they present the processed Ag, thereby inducing immune
      responses. Numerous studies indicated that immunotherapies utilizing DC
      presenting tumor-associated antigens can safely be administered to cancer
      patients and induce significant immunologic and clinical responses. Moreover, it
      has been demonstrated that DCs are related to clinical stage, invasion,
      metastasis and prognosis of gastric cancer. DC-based tumor vaccines become a new
      effective immunoadjuvant therapy for gastric cancer.

PMID- 16285896
TI  - Isolation of Nanjing local strains of HHV-7 and their biological and
      immunological characteristics.
AB  - To investigate the biological and immunological characteristics of the Nanjing
      local strains of HHV-7, four strains of herpesvirus were isolated from saliva
      specimens of one healthy individual and three children suffering from a kidney
      disease in Nanjing. The viruses were identified by transmission electron
      microscopy (EM), indirect immunofluorescence assay (IFA) with a specific
      monoclonal antibody; nested polymerase chain reaction, restriction mapping and
      DNA sequencing. The virus-infected cells showed the typical cytophathic effect
      (CPE) under microscopy and could be detected by IFA with the human herpesvirus-7
      (HHV-7) specific antibody. Under EM, herpesvirus-like and virions capsids could
      be found in their cytoplasm or nucleoplasm. HHV-7 DNA fragments amplified from
      infected cells by nested PCR were confirmed by restriction mapping and DNA
      sequencing. Similarly to DC strain, an known HHV-7 strain used in the present
      study as the positive control, the virus could be inactivated by ultraviolet
      irradiation for 10 min, heated at 45 centigrade degree for 30 min, pH<5 or>9 at 4
      centigrade degree for 2 h and ether or chloroform for 10 h. The virus induced the
      production of TNF-alpha, IL-10 and IL-12 p 70 while inhibited IFN-alpha
      secretion, increased the percentage of CD2(+) cells while decreased that of
      CD4(+) or CD 45 RA(+) cells. The results indicate that the viruses isolated in
      Nanjing are HHV-7, which has similar biological characteristic to the known HHV-7
      strain, DC. Infection with HHV-7 in vitro could affect immune function of
      lymphocytes by disturbing cytokine production and CD antigen expression.

PMID- 16285895
TI  - Global gene expression profiling in interleukin-12-induced activation of CD8(+)
      cytotoxic T lymphocytes against mouse mammary Carcinoma.
AB  - Interleukin-12 (IL-12) is a critical cytokine representing the link between the
      cellular and humoral branches of host immune defense apparatus. IL-12-induced
      cytotoxic lymphocyte (CTL) development is a central mechanism in immune responses
      against intracellular infectious agents as well as malignant growth. However, the
      molecular basis of tumor-specific CTL responses mediated by IL-12 remains poorly
      defined. In this study, we addressed this issue in a comprehensive manner to
      probe into IL-12-induced anti-tumor responses by global gene expression profiling
      of mRNA expression in CD8(+) T cells in a transplantable syngeneic mouse mammary
      carcinoma model treated or not with recombinant IL-12. A strong tumor regression
      was induced by the IL-12 treatment. An introspection of differential gene
      expression at an early stage of the IL-12-initiated CTL activation reveals
      interesting genes and molecular pathways that may account for the marked tumor
      regression, and is likely to provide a rich source of potential targets for
      further research and development of effective therapeutic modalities.

PMID- 16285897
TI  - Lipopolysaccharide could be internalized into human peripheral blood mononuclear
      cells and elicit TNF-alpha release, but not via the pathway of toll-like receptor
      4 on the cell surface.
AB  - Lipopolysaccharide (LPS), the principal component of the outer membrane of Gram
      negative bacteria, stimulates various cell types to release numerous
      proinflammatory mediators such as TNF-alpha, IL-6 and IL-12, which may damage
      cells and lead to organ injury, even sepsis and septic shock. Toll-like receptor
      4 (TLR4) has been identified as the receptor involved in the recognition of LPS,
      but the role of LPS uptake in activating signal transduction remains
      controversial. In the present study, TNF-alpha was used as a marker of
      macrophages/ monocytes activated by LPS, and CQ was used as an inhibitor of
      endosome mature in order to definitude what stage of the signal transduction
      elicited by LPS was interrupted. We found that there indeed existed
      internalization of LPS and internalization partially participated in LPS
      signaling since CQ inhibited cytokine release, and decreased accumulation of FITC
      LPS in hPBMCs. In contrast, anti-hTLR4 antibody could decrease cytokine release,
      but had no inhibition on accumulation of FITC-LPS. This result revealed that
      inhibition of cytokine release was related to reduction of FITC-LPS accumulation
      in the cells. But TLR4 on the cell surface couldn't participate in
      internalization of LPS. Thus, LPS signaling and internalization couldn't be
      viewed as mutually independent processes.

PMID- 16285898
TI  - The expression and distribution of S-100 protein and CD 83 in thyroid tissues of
      autoimmune thyroid diseases.
AB  - To investigate the expression and distribution of S-100 protein and CD 83 in the
      thyroid tissues of autoimmune thyroid diseases (ATDs), and to study the role of
      the dendritic cells in the pathogenesis of ATDs, immunohistochemical staining was
      used on pathological tissues of 20 patients with Hashimoto's thyroiditis (HT) and
      20 patients with Graves' disease (GD) to check the expression and distribution of
      S-100 protein and CD 83. Compared with control group (20 cases of thyroid
      follicular adenoma, TFA), the higher expressions of S-100 in HT (139.38+/-5.92 vs
      59.47+/-11.69) and GD (119.42+/-14.48 vs 59.47+/-11.69) were observed
      respectively (p<0.001). The increased positive expressions of CD 83 which is
      known as a marker of mature and activated DCs in HT (22.58+/-13.96 vs 5.19+/
      8.08) and GD (29.92 +/-14.43 vs 5.19+/-8.08) were also found respectively
      (p<0.001). Serum TPO antibody (TPO-Ab, 67.3+/-11.6%) and Tg antibody (Tg-Ab,
      59.8+/-10.1%) in HT were higher than those in GD (28.4+/-5.7%, 23.1+/-4.9%) and
      TFA (6.1+/-3.4%, 7.2 +/-4.6%) (p<0.01). Serum TR-Ab in GD (16.3+/-5.6 U/L) was
      higher than those in HT (4.8+/- 2.3 U/L) and TFA (2.5+/-1.2 U/L) (p<0.01). Our
      findings suggest that the high expression of DCs' markers may be related to the
      pathogenesis of HT and GD. The upregulation of both the number and the matured
      functions of DCs, may lead to present more antigens and to produce more auto
      antibodies (such as Tg-Ab and TPO-Ab in HT, TR-Ab in GD), which may be involved
      in pathogenesis of the autoimmune thyroid diseases.

PMID- 16285899
TI  - FADDdel-GFP modified mouse insulinoma cells counteract the cytotoxicity of
      reactive T cells.
AB  - IDDM results from pancreatic beta cell destruction by islet-reactive T cells, a
      process that involves beta cell apoptosis. Fas-FasL pathway plays a major role in
      pancreatic beta cell death. Fas-associated death domain protein (FADD), the
      component of the tumor necrosis factor receptor type 1 (TNFR1) and Fas signaling
      complexes, is involved in TNFR1- and Fas-induced apoptosis. Inhibiting the
      function of FADD will lead to blocking downstream apoptosis signal, which
      protects pancreatic beta cells from destruction by Fas-FasL pathway. In this
      study we constructed eukaryotic expressing vector of fusional protein FADDdel-GFP
      named pFADDdel-GFP. After pFADDdel-GFP was transfected into NIT, the expression
      of FADDdel-GFP in NIT was detected by fluorescence microscopy and the resistance
      of NIT transfected with pFADDdel-GFP to cytotoxicity mediated by special T cells
      was detected by FACS and MTT. The results showed that NIT modified by pFADDdel
      GFP obviously resisted cytotoxicity mediated by special T cells. Therefore, it
      may be useful in the prevention or treatment of IDDM by intervening Fas-FasL
      pathway.

PMID- 16285900
TI  - Evaluation of a rat model of experimental autoimmune encephalomyelitis with human
      MBP as antigen.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a good model for human
      multiple sclerosis (MS) research. However, there are some defects in the
      traditional models. Here, we improved the model by using the human myelin basic
      protein (MBP) as antigen. EAE was induced by immunization of female Wistar rats
      with human MBP. Compared with the traditional models, the new model was evaluated
      by clinical signs to pathological changes. The immune state of the model was
      assessed by the lymphocyte infiltrative response and levels of TNF-alpha, IFN
      gamma, IL-10. It was found that most of rats exhibited tail tone loss and hind
      limb paralysis, also there were demyelination, infiltrative lymphocyte foci,
      "neuronophagia" in the cortex of cerebra and the white matter of spinal cords.
      PBMCs and spleen lymphocytes were strongly responsive to the stimulation of MBP
      and PHA. The levels of TNF-alpha and IFN-gamma were altered with the severity of
      EAE. In the remitting phase, IL-10 was increased significantly. This study
      demonstrates that the animal model of EAE induced by human MBP bears resemblance
      to the features of human multiple sclerosis and promises to be a better model
      than ever before for the study of MS.

PMID- 16285901
TI  - Lanthanum inhibited the binding of LPS with monocyte and CD 14 expression
      upregulation.
AB  - To investigate the effects of lanthanum chloride on binding of LPS to monocyte
      and CD 14 expression upregulation induced by LPS, human monocytes were analyzed
      by flow cytometry (FCM). The results indicated that lanthanum chloride could
      decrease the binding rate of LPS with monocyte significantly. LPS upregulated the
      expression of CD 14 on monocyte in a dose dependant manner, however, lanthanum
      chloride could inhibit the increase of CD 14 expression on monocytes by halves.

PMID- 16285902
TI  - Real-time detection of circulating apoptotic cells by in vivo flow cytometry.

PMID- 16285903
TI  - Practical vessel imaging by computed tomography in live transgenic mouse models
      for human tumors.
AB  - Contrast-enhanced small-animal computed tomography is an economical and highly
      quantitative tool for serially examining tumor development in situ, for analyzing
      the network of blood vessels that nourish them, and for following the response of
      tumors to preclinical therapeutic intervention(s). We present practical
      considerations for visualizing the vascular network of transgenic mouse tumors.
      Using a long-acting iodinated triglyceride blood-pool contrast agent, we present
      optimized scanner acquisition parameters and volume-rendering techniques for
      examining the intermediate and large vessels of complex spontaneous tumors (e.g.,
      alveolar rhabdomyosarcomas) in transgenic mice. Our findings indicate that
      multiple-frame, 360-720 view acquisitions were mandatory for clarifying bone and
      soft tissue from vessel contrast. This finding was consistent in visualizations
      using a one-dimensional transfer function where voxel color and opacity was
      assigned in proportion to CT value and a two-dimensional transfer function where
      voxel color and opacity was assigned in proportion to CT value and gradient
      magnitude. This study lays a groundwork for the qualitative and quantitative
      assessment of anti-angiogenesis preclinical studies using transgenic mice.

PMID- 16285904
TI  - MIPortal: a high capacity server for molecular imaging research.
AB  - The introduction of novel molecular tools in research and clinical medicine has
      created a need for more refined information management systems. This article
      describes the design and implementation of such a new information platform: the
      Molecular Imaging Portal (MIPortal). The platform was created to organize,
      archive, and rapidly retrieve large datasets using Web-based browsers as access
      points. The system has been implemented in a heterogeneous, academic research
      environment serving Macintosh, Unix, and Microsoft Windows clients and has been
      shown to be extraordinarily robust and versatile. In addition, it has served as a
      useful tool for clinical trials and collaborative multi-institutional small
      animal imaging research.

PMID- 16285905
TI  - In vivo imaging of peripheral benzodiazepine receptors in mouse lungs: a
      biomarker of inflammation.
AB  - The ability to visualize the immune response with radioligands targeted to immune
      cells will enhance our understanding of cellular responses in inflammatory
      diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and
      neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a
      model of inflammation to assess whether the PBR could be used as a noninvasive
      marker of inflammation in the lungs. Planar imaging of mice administrated 10 or
      30 mg/kg LPS showed increased [(123)I]-(R)-PK11195 radioactivity in the thorax 2
      days after LPS treatment relative to control. Following imaging, lungs from
      control and LPS-treated mice were harvested for ex vivo gamma counting and showed
      significantly increased radioactivity above control levels. The specificity of
      the PBR response was determined using a blocking dose of nonradioactive PK11195
      given 30 min prior to radiotracer injection. Static planar images of the thorax
      of nonradioactive PK11195 pretreated animals showed a significantly lower level
      of radiotracer accumulation in control and in LPS-treated animals (p < .05).
      These data show that LPS induces specific increases in PBR ligand binding in the
      lungs. We also used in vivo small-animal PET studies to demonstrate increased
      [(11)C]-(R)-PK11195 accumulation in the lungs of LPS-treated mice. This study
      suggests that measuring PBR expression using in vivo imaging techniques may be a
      useful biomarker to image lung inflammation.

PMID- 16285906
TI  - Near-infrared optical imaging of ovarian cancer xenografts with novel alpha 3
      integrin binding peptide "OA02".
AB  - Through screening of random one-bead one-compound (OBOC) libraries, we previously
      identified cyclic peptides with the cDGXGXXc motif that bind to alpha3 integrin
      subunit on ovarian adenocarcinoma cell lines ES-2, SKOV-3, and CaOV-3. We
      subsequently synthesized two secondary libraries based on this motif and
      identified new peptides that bound with a higher affinity to these cell lines.
      One of the peptides identified from the 20% "down-substituted" focused library
      was the c-dGHCitGPQ-c ("OA02") peptide. The goal of this study was to determine
      whether this peptide labeled with near-infrared probes could be detected after
      intravenous injection in ovarian tumor-bearing mice and if it would selectively
      localize in the tumor. Three different forms of this peptide were synthesized,
      "OA02"-biotin (noncovalently linked to streptavidin-Cy5.5); "OA02"-Cy5.5 and
      "OA02"-AlexaFluo 680. Using a KODAK IS2000MM image station, these peptide probes
      were used at the near-infrared (NIR) spectra to image nude mice bearing ES-2
      (alpha3 integrin positive) and Raji (alpha3 integrin negative) xenografts. The
      peptide probe displayed highly specific tumor uptake within 15 min, which lasted
      for 70 min for "OA02"-Cy5.5 and "OA02"-AlexaFluo 680 and for 24 hours for "OA02"
      biotin-streptavidin-Cy5.5. Some kidney and bladder signal were noted. Prior
      injection with anti-alpha3 monoclonal antibody blocked the binding of this
      peptide to the ES-2 tumors.

PMID- 16285907
TI  - High-affinity near-infrared fluorescent small-molecule contrast agents for in
      vivo imaging of prostate-specific membrane antigen.
AB  - Surgical resection remains a definitive treatment for prostate cancer. Yet,
      prostate cancer surgery is performed without image guidance for tumor margin,
      extension beyond the capsule and lymph node positivity, and without verification
      of other occult metastases in the surgical field. Recently, several imaging
      systems have been described that exploit near-infrared (NIR) fluorescent light
      for sensitive, real-time detection of disease pathology intraoperatively. In this
      study, we describe a high-affinity (9 nM), single nucleophile-containing, small
      molecule specific for the active site of the enzyme PSMA. We demonstrate
      production of a tetra-sulfonated heptamethine indocyanine NIR fluorescent
      derivative of this molecule using a high-yield LC/MS purification strategy.
      Interestingly, NIR fluorophore conjugation improves affinity over 20-fold, and we
      provide mechanistic insight into this observation. We describe the preparative
      production of enzymatically active PSMA using a baculovirus expression system and
      an adenovirus that co-expresses PSMA and GFP. We demonstrate sensitive and
      specific in vitro imaging of endogenous and ectopically expressed PSMA in human
      cells and in vivo imaging of xenograft tumors. We also discuss chemical
      strategies for improving performance even further. Taken together, this study
      describes nearly complete preclinical development of an optically based small
      molecule contrast agent for image-guided surgery.

PMID- 16285908
TI  - Micro-PET/CT monitoring of herpes thymidine kinase suicide gene therapy in a
      prostate cancer xenograft: the advantage of a cell-specific transcriptional
      targeting approach.
AB  - Cancer gene therapy based on tissue-restricted expression of cytotoxic gene
      should achieve superior therapeutic index over an unrestricted method. This study
      compared the therapeutic effects of a highly augmented, prostate-specific gene
      expression method to a strong constitutive promoter-driven approach. Molecular
      imaging was coupled to gene therapy to ascertain real-time therapeutic activity.
      The imaging reporter gene (luciferase) and the cytotoxic gene (herpes simplex
      thymidine kinase) were delivered by adenoviral vectors injected directly into
      human prostate tumors grafted in SCID mice. Serial bioluminescence imaging,
      positron emission tomography, and computed tomography revealed restriction of
      gene expression to the tumors when prostate-specific vector was employed. In
      contrast, administration of constitutive active vector resulted in strong signals
      in the liver. Liver serology, tissue histology, and frail condition of animals
      confirmed liver toxicity suffered by the constitutive active cohorts, whereas the
      prostate-targeted group was unaffected. The extent of tumor killing was analyzed
      by apoptotic staining and human prostate marker (prostate-specific antigen).
      Overall, the augmented prostate-specific expression system was superior to the
      constitutive approach in safeguarding against systemic toxicity, while achieving
      effective tumor killing. Integrating noninvasive imaging into cytotoxic gene
      therapy will provide a useful strategy to monitor gene expression and therapeutic
      efficacy in future clinical protocols.

PMID- 16285909
TI  - ntPET: a new application of PET imaging for characterizing the kinetics of
      endogenous neurotransmitter release.
AB  - We present a new application of positron emission tomography ("ntPET" or
      "neurotransmitter PET") designed to recover temporal patterns of neurotransmitter
      release from dynamic data. Our approach employs an enhanced tracer kinetic model
      that describes uptake of a labeled dopamine D2/D3 receptor ligand in the presence
      of a time-varying rise and fall in endogenous dopamine. Data must be acquired
      during both baseline and stimulus (transient dopamine release) conditions. Data
      from a reference region in both conditions are used as an input function, which
      alleviates the need for any arterial blood sampling. We use simulation studies to
      demonstrate the ability of the method to recover the temporal characteristics of
      an increase in dopamine concentration that might be expected following a drug
      treatment. The accuracy and precision of the method-as well as its potential for
      false-positive responses due to noise or changes in blood flow-were examined.
      Finally, we applied the ntPET method to small-animal imaging data in order to
      produce the first noninvasive assay of the time-varying release of dopamine in
      the rat striatum following alcohol.

PMID- 16285910
TI  - Effect of dietary energy source on energy balance, production, metabolic
      disorders and reproduction in lactating dairy cattle.
AB  - The pathway for oxidation of energy involves a balanced oxidation of C2 and C3
      compounds. During early lactation in dairy cattle this C2/C3 ratio is out of
      balance, due to a high availability of lipogenic (C2) products and a low
      availability of glycogenic (C3) products relative of the C2 and C3 products
      required for milk production. This review compares studies which manipulated
      dietary energy source and shows that dietary energy source can affect the balance
      of the C2/C3 ratio, as indicated by plasma NEFA, beta-hydroxybutyrate (BHBA) and
      glucose levels. It is shown that glycogenic nutrients increase glucose and
      insulin concentrations and decrease NEFA and BHBA plasma levels. Extra lipogenic
      nutrients elevate NEFA and BHBA and decrease plasma glucose concentrations.
      Lipogenic nutrients generally increase milk fat percentage and decrease milk
      protein percentage, suggesting a surplus of C2 compounds. The inverse is the case
      for feeding extra glycogenic nutrients, implying reduced deamination and
      oxidation of glycogenic amino acids. Feeding extra glycogenic nutrients improved
      the energy balance (EB), in contrast to ambiguous results of lipogenic nutrients
      on EB. Moreover, glycogenic feed may reduce the severity of ketosis and fatty
      liver, but increased the incidence of (sub)clinical acidosis. Since studies are
      scarce, it seems difficult to draw conclusions on the effects of dietary energy
      source on reproduction. However, lipogenic nutrients decrease glucose and
      increase NEFA and BHBA plasma levels. High plasma NEFA and BHBA and low plasma
      glucose levels are associated with decreased reproductive performance, which
      might imply the C2/C3 compound balance to be important for reproductive function.

PMID- 16285911
TI  - The effects of progesterone priming on reproductive performance of GnRH-PGF2alpha
      treated anestrous goats.
AB  - The objective of this experiment was to determine the effect of a 5-day
      progesterone priming prior to a GnRH-PGF2alpha treatment on reproductive
      performance of anestrous goats. Thirty-six Mountain Black goats were randomly
      assigned in a 2 x 2 factorial arrangement and were administered intravaginally on
      day -12, either with 300 mg progesterone inserts (CGPE and CGP) or with 0 mg
      progesterone (GPE and GP) for 5 days. On day -6, the goats were injected with 100
      microg GnRH, followed 6 days later by 15 mg PGF2alpha (day 0), the time at which
      the goats in the CGPE and GPE groups were administered 300 IU eCG injections and
      those in CGP and GP groups were administered the control solution. The goats were
      exposed to four fertile bucks at 0 h and were checked for breeding marks at 6-h
      intervals for 72 h. Blood samples were collected from all goats for progesterone
      analysis. Progesterone concentrations increased only in CGPE and CGP during the
      period of device insertion but remained low in GPE and GP groups (P < 0.001).
      Progesterone levels at the time of GnRH injection on day -6 were basal (0.2 +/-
      0.04 ng.mL-1) among the groups and began to increase starting on day -2. Day 0
      progesterone concentrations differed (P < 0.05) among groups and were
      significantly influenced by CIDR-G (P < 0.001). A similar proportion of goats
      expressed estrus and intervals to detected estrus were shorter (P < 0.05) in the
      CGPE and GPE groups than in GP with no difference between the CGPE, CGP and GPE
      or between CGP and GP groups. The number of goats ovulating based upon elevated
      progesterone levels on day 0 was significantly greater (P = 0.002) in CGPE (9/9)
      and CGP (9/9) than GPE (6/9) and GP (5/9) groups and was significantly influenced
      by CIDR-G (P = 0.03). All pregnant goats had elevated progesterone concentration
      on day 0 and none of the goats with basal progesterone levels became pregnant.
      Pregnancy and kidding rates, twinning percentage and the number of kids born per
      goat exposed were greater (P < 0.05) among goats treated with progesterone and
      eCG. In conclusion, progesterone priming and eCG are essential for producing
      higher rates of pregnancy and kidding in GnRH-PGF2alpha-treated anestrous goats.

PMID- 16285912
TI  - Comparison of an oestrus synchronisation protocol with oestradiol benzoate and
      PGF2alpha and insemination at detected oestrus to a timed insemination protocol
      (Ovsynch) on reproductive performance of lactating dairy cows.
AB  - A total of 226 out of 245 postpartum lactating dairy cows in a commercial dairy
      farm were allocated to two groups of oestrous synchronisation protocols in order
      to evaluate reproductive performance. One group was treated with oestradiol
      benzoate (ODB) and PGF2alpha on day 10 of the oestrous cycle with insemination at
      the detected oestrus, the second group underwent the Ovsynch (OVS) protocol (GnRH
      + PGF2alpha + GnRH) with timed AI. Pregnancy was diagnosed by ultrasonography on
      day 28 after AI and confirmed by rectal palpation on day 45. A higher (P < 0.001)
      proportion of cows in OVS (100%) were inseminated within (19.2 +/- 3.8 h)
      following the second GnRH injection than those of cows in EPE (ODB + PGF2alpha +
      ODB) (70.6%) inseminated at the detected oestrus within (35.6 +/- 5.2 h)
      following the second ODB injection. Pregnancy rates for the first AI at day 28
      (64.0 +/- 4.6, 62.4 +/- 5.5%) and at day 45 post-insemination (40.4 +/- 4.7, 40.0
      +/- 5.6%) for OVS and EPE cows respectively, did not differ between the two
      treatments, whereas, the overall pregnancy rates tended to be higher (P < 0.08)
      for the OVS (85.1 +/- 3.8%) cows than the EPE cows (74.1 +/- 4.5%). No
      differences were observed in pregnancy rates for first AI and overall up to
      fourth AI between primiparous (34.7 +/- 5.8 and 85.3 +/- 4.7%) and multiparous
      cows (43.5 +/- 4.5 and 77.4 +/- 3.6%). Days open for pregnant cows tended to be
      lower (P < 0.08) for OVS (76.2 +/- 3) than for EPE cows (84.7 +/- 4), while days
      open were higher (P < 0.05) in primiparous cows (85.3 +/- 4) than in multiparous
      cows (75.6 +/- 3). The results indicate that pregnancy rates for first AI were
      similar, but overall pregnancy rates up to the fourth AI tended to be higher for
      OVS than EPE cows, while days open was tended to be lower for OVS than EPE cows.

PMID- 16285913
TI  - The effects of dietary phytoestrogens on aromatase activity in human endometrial
      stromal cells.
AB  - Dietary phytoestrogens have been reported to inhibit aromatase activity in
      placental microsomes, but the effects in the human endometrium are unknown.
      Aromatase, the rate-limiting enzyme in the conversion of androgens to estrogens,
      has recently been shown to be expressed in the endometrium of women with
      endometriosis and is thought to play a role in the pathophysiology of this
      disease. Therefore, the objective of this study was to screen dietary
      phytoestrogens for their ability to inhibit aromatase activity in human
      endometrial stromal cells (ESC) and identify potential novel therapeutic agents
      for the treatment of endometriosis. The inhibition of aromatase activity by
      direct interaction with the dietary phytoestrogens genistein, daidzein, chrysin,
      and naringenin was tested in a cell free assay. Furthermore, test compound
      effects on aromatase activity in ESC cultures were also examined. Genistein and
      daidzein were inactive in the human recombinant aromatase assay whereas
      naringenin and chrysin inhibited aromatase activity. However, genistein (1 nM to
      1 mM) stimulated aromatase activity in ESC whereas other phytoestrogens had no
      effect. Immunopositive aromatase cells were demonstrated in genistein-treated ESC
      but not in untreated control cultures. Taken together, our data suggest that
      genistein can increase aromatase activity in ESC likely via increased enzyme
      expression.

PMID- 16285914
TI  - Dietary supplementation with safflower seeds differing in fatty acid composition
      differentially influences serum concentrations of prostaglandin F metabolite in
      postpartum beef cows.
AB  - Synthesis and secretion of prostaglandin F2alpha (PGF2alpha) is elevated
      following parturition and exerts divergent effects on the re-establishment of
      fertile estrous cycles in cows. The objective of these experiments was to
      determine if oil seed supplements differing in fatty acid composition
      differentially influence serum concentrations of the specific PGF2alpha
      metabolite, PGFM. Safflower seed supplements were formulated to provide 5% of dry
      matter intake as fat. In Trial 1, 24 multiparous beef cows were individually fed
      control (beet pulp-soybean meal) or cracked high-linoleate safflower seed (78%
      18:2n-6) supplements for 80 d postpartum. Linoleate supplemented cows had greater
      (P < 0.001) serum concentrations of PGFM than control cows. In Trial 2,
      primiparous beef cows (n = 36) were individually fed control (cracked corn
      soybean meal), cracked high-linoleate (76% 18:2n-6) or -oleate (72% 18:1n-9)
      safflower seed supplements for 92 d postpartum. As in Trial 1, serum
      concentrations of PGFM were greater (P < or = 0.04) in linoleate than control or
      oleate supplemented cows. Serum concentrations of PGFM, however, did not differ
      (P = 0.40) among oleate and control supplemented cows. Although potential impacts
      on reproductive performance remain to be proven, dietary oil supplements high in
      linoleate, but not oleate, increased serum concentrations of PGFM compared to
      control supplements.

PMID- 16285916
TI  - Sigma and RNA polymerase: an on-again, off-again relationship?
AB  - In bacteria, a fundamental level of gene regulation occurs by competitive
      association of promoter-specificity factors called sigmas with RNA polymerase
      (RNAP). This sigma cycle paradigm underpins much of our understanding of all
      transcriptional regulation. Here, we review recent challenges to the sigma cycle
      paradigm in the context of its essential features and of the structural basis of
      sigma interactions with RNAP and elongation complexes. Although sigmas can play
      dual roles as both initiation and elongation regulators, we suggest that the key
      postulate of the sigma cycle, that sigmas compete for binding to RNAP after each
      round of RNA synthesis, remains the central mechanism for programming
      transcription initiation in bacteria.

PMID- 16285917
TI  - Retention of transcription initiation factor sigma70 in transcription elongation:
      single-molecule analysis.
AB  - We report a single-molecule assay that defines, simultaneously, the
      translocational position of a protein complex relative to DNA and the subunit
      stoichiometry of the complex. We applied the assay to define translocational
      positions and sigma70 contents of bacterial transcription elongation complexes in
      vitro. The results confirm ensemble results indicating that a large fraction,
      approximately 70%-90%, of early elongation complexes retain sigma70 and that a
      determinant for sigma70 recognition in the initial transcribed region increases
      sigma70 retention in early elongation complexes. The results establish that a
      significant fraction, approximately 50%-60%, of mature elongation complexes
      retain sigma70 and that a determinant for sigma70 recognition in the initial
      transcribed region does not appreciably affect sigma70 retention in mature
      elongation complexes. The results further establish that, in mature elongation
      complexes that retain sigma70, the half-life of sigma70 retention is long
      relative to the time-scale of elongation, suggesting that some complexes may
      retain sigma70 throughout elongation.

PMID- 16285918
TI  - Holoenzyme switching and stochastic release of sigma factors from RNA polymerase
      in vivo.
AB  - We investigated the binding of E. coli RNA polymerase holoenzymes bearing
      sigma70, sigma(S), sigma32, or sigma54 to the ribosomal RNA operons (rrn) in
      vivo. At the rrn promoter, we observed "holoenzyme switching" from Esigma70 to
      Esigma(S) or Esigma32 in response to environmental cues. We also examined if
      sigma factors are retained by core polymerase during transcript elongation. At
      the rrn operons, sigma70 translocates briefly with the elongating polymerase and
      is released stochastically from the core polymerase with an estimated half-life
      of approximately 4-7 s. Similarly, at gadA and htpG, operons that are targeted by
      Esigma(S) and Esigma32, respectively, we find that sigma(S) and sigma32 also
      dissociate stochastically, albeit more rapidly than sigma70, from the elongating
      core polymerase. Up to approximately 70% of Esigma70 (the major vegetative
      holoenzyme) in rapidly growing cells is engaged in transcribing the rrn operons.
      Thus, our results suggest that at least approximately 70% of cellular holoenzymes
      release sigma70 during transcript elongation. Release of sigma factors during
      each round of transcription provides a simple mechanism for rapidly reprogramming
      polymerase with the relevant sigma factor and is consistent with the occurrence
      of a "sigma cycle" in vivo.

PMID- 16285919
TI  - MRE11/RAD50 cleaves DNA in the AID/UNG-dependent pathway of immunoglobulin gene
      diversification.
AB  - MRE11/RAD50/NBS1 (MRN) is a ubiquitous complex that participates in the response
      to DNA damage and in immunoglobulin (Ig) gene diversification. Ig gene
      diversification is initiated by deamination of cytosine to uracil, followed by
      removal of uracil to create an abasic (AP) site. We find that MRE11 associates
      specifically with rearranged Ig genes in hypermutating B cells, whereas APE1, the
      major AP-endonuclease in faithful base excision repair, does not. We show that
      purified, recombinant MRE11/RAD50 can cleave DNA at AP sites and that this AP
      lyase activity is conserved from humans to Archaea. MRE11/RAD50 cleaves at AP
      sites within single-stranded regions of DNA, suggesting that at transcribed Ig
      genes, cleavage may be coordinated with deamination by AID and deglycosylation by
      UNG2 to produce single-strand breaks (SSBs) that undergo subsequent mutagenic
      repair and recombination. These results identify MRN with DNA cleavage in the AID
      initiated pathway of Ig gene diversification.

PMID- 16285920
TI  - Assembly of a double hexameric helicase.
AB  - Viral initiators perform multiple functions in initiation of DNA replication
      including ori binding, melting, and unwinding, culminating in the formation of a
      double hexameric (DH) helicase. We have recapitulated the assembly of the
      papillomavirus E1 initiator DH helicase, providing the first description of how
      such a complex is formed. We have identified an intermediate, a double trimer
      (DT), which relies on two cooperating DNA binding activities to melt double
      stranded DNA and generate a substrate for formation of the DH helicase. The
      formation of the DT is dependent on nucleotide binding, while formation of the DH
      also requires hydrolysable ATP. The DNA binding properties of the DT explain how
      E1, which binds to DNA as a dimer, can effect a transition to ring structures,
      such as the double hexamer. These results provide new insight into the intricate
      machinery that initiates DNA replication.

PMID- 16285921
TI  - Crosstalk between primase subunits can act to regulate primer synthesis in trans.
AB  - The coordination of primase function within the replisome is an essential but
      poorly understood feature of lagging strand synthesis. By using crystallography
      and small-angle X-ray scattering (SAXS), we show that functional elements of
      bacterial primase transition between two dominant conformations: an extended form
      that uncouples a regulatory domain from its associated RNA polymerase core and a
      compact state that sequesters the regulatory region from the site of primer
      synthesis. FRET studies and priming assays reveal that the regulatory domain of
      one primase subunit productively associates with nucleic acid that is bound to
      the polymerase domain of a second protomer in trans. This intersubunit
      interaction allows primase to select initiation sites on template DNA and
      implicates the regulatory domain as a "molecular brake" that restricts primer
      length. Our data suggest that the replisome may cooperatively use multiple
      primases and this conformational switch to control initiation frequency,
      processivity, and ultimately, Okazaki fragment synthesis.

PMID- 16285922
TI  - A deletion site editing endonuclease in Trypanosoma brucei.
AB  - RNA editing in Trypanosoma brucei inserts and deletes uridines in mitochondrial
      mRNAs by a series of enzymatic steps that are catalyzed by a multiprotein
      complex, the editosome. KREPB1 and two related editosome proteins KREPB2 and
      KREPB3 contain motifs that suggest endonuclease and RNA/protein interaction
      functions. Repression of KREPB1 expression in procyclic forms by RNAi inhibited
      growth, in vivo editing, and in vitro endoribonucleolytic cleavage of deletion
      substrates. However, cleavage of insertion substrates and the exoUase, TUTase,
      and ligase catalytic activities of editing were retained by 20S editosomes.
      Repression of expression of an ectopic KREPB1 allele in bloodstream forms lacking
      both endogenous alleles or exclusive expression of KREPB1 with point mutations in
      the putative RNase III catalytic domain also blocked growth, in vivo editing, and
      abolished cleavage of deletion substrates, without affecting the other editing
      steps. These data indicate that KREPB1 is an endoribonuclease that is specific
      for RNA editing deletion sites.

PMID- 16285923
TI  - Dephosphorylation-dependent sorting of SR splicing factors during mRNP
      maturation.
AB  - SR proteins are a family of sequence-specific RNA binding proteins originally
      discovered as essential factors for pre-mRNA splicing and recently implicated in
      mRNA transport, stability, and translation. Here, we used a genetic
      complementation system derived from conditional knockout mice to address the
      function and regulation of SR proteins in vivo. We demonstrate that ASF/SF2 and
      SC35 are each required for cell viability, but, surprisingly, the effector RS
      domain of ASF/SF2 is dispensable for cell survival in MEFs. Although shuttling SR
      proteins have been implicated in mRNA export, prevention of ASF/SF2 from
      shuttling had little impact on mRNA export. We found that shuttling and
      nonshuttling SR proteins are segregated in an orderly fashion during mRNP
      maturation, indicating distinct recycling pathways for different SR proteins. We
      further showed that this process is regulated by differential dephosphorylation
      of the RS domain, thus revealing a sorting mechanism for mRNP transition from
      splicing to export.

PMID- 16285924
TI  - A protein component at the heart of an RNA machine: the importance of protein l27
      for the function of the bacterial ribosome.
AB  - Deletion of the gene for protein L27 from the E. coli chromosome results in
      severe defects in cell growth. This deficiency is corrected by the expression of
      wild-type (wt) protein L27 from a plasmid. Examination of strains expressing L27
      variants truncated at the N terminus reveals that the absence of as few as three
      amino acids leads to a decrease in growth rate, an impairment in peptidyl
      transferase activity, and a sharp decline in the labeling of L27 from the 3' end
      of a photoreactive tRNA at the ribosomal P site. These findings suggest that the
      flexible N-terminal sequence of L27, which protrudes onto the interface of the
      bacterial 50S subunit, can reach the peptidyl transferase active site and
      contribute to its function, possibly by helping to correctly position tRNA
      substrates at the catalytic site.

PMID- 16285925
TI  - Structural insights into the roles of water and the 2' hydroxyl of the P site
      tRNA in the peptidyl transferase reaction.
AB  - Peptide bond formation is catalyzed at the peptidyl transferase center (PTC) of
      the large ribosomal subunit. Crystal structures of the large ribosomal subunit of
      Haloarcula marismortui (Hma) complexed with several analogs that represent either
      the substrates or the transition state intermediate of the peptidyl transferase
      reaction show that this reaction proceeds through a tetrahedral intermediate with
      S chirality. The oxyanion of the tetrahedral intermediate interacts with a water
      molecule that is positioned by nucleotides A2637 (E. coli numbering, 2602) and
      (methyl)U2619(2584). There are no Mg2+ ions or monovalent metal ions observed in
      the PTC that could directly promote catalysis. The A76 2' hydroxyl of the
      peptidyl-tRNA is hydrogen bonded to the alpha-amino group and could facilitate
      peptide bond formation by substrate positioning and by acting as a proton shuttle
      between the alpha-amino group and the A76 3' hydroxyl of the peptidyl-tRNA.

PMID- 16285926
TI  - Ribosome occupancy of the yeast CPA1 upstream open reading frame termination
      codon modulates nonsense-mediated mRNA decay.
AB  - Saccharomyces cerevisiae CPA1 mRNA contains an upstream open reading frame (uORF)
      encoding the arginine attenuator peptide (AAP). Negative translational regulation
      of CPA1 occurs when the nascent AAP responds to arginine (Arg) by stalling
      ribosomes at the uORF termination codon. CPA1 expression is also controlled by
      nonsense-mediated mRNA decay (NMD). Using wild-type and decay-defective strains
      expressing CPA1-LUC, we determined how this uORF contributes to NMD control. Arg
      addition to media rapidly destabilized the CPA1 transcript in wild-type but not
      upf1delta cells. The wild-type uORF exerted translational control and induced NMD
      of CPA1-LUC; the mutated D13N uORF, which eliminates stalling and regulation, did
      not. Thus, regulation by NMD was not governed simply by ribosomes encountering
      the uORF terminator but appeared dependent on the AAP's ribosome-stalling
      ability. Improving the D13N uORF initiation context also promoted NMD. Hence, NMD
      appears to be triggered by increased ribosomal occupancy of the uORF termination
      codon.

PMID- 16285927
TI  - Structural framework for the mechanism of archaeal exosomes in RNA processing.
AB  - Exosomes emerge as central 3'-->5' RNA processing and degradation machineries in
      eukaryotes and archaea. We determined crystal structures of two 230 kDa nine
      subunit archaeal exosome isoforms. Both exosome isoforms contain a hexameric ring
      of RNase phosphorolytic (PH) domain subunits with a central chamber. Tungstate
      soaks identified three phosphorolytic active sites in this processing chamber. A
      trimer of Csl4 or Rrp4 subunits forms a multidomain macromolecular interaction
      surface on the RNase-PH domain ring with central S1 domains and peripheral KH and
      zinc-ribbon domains. Structural and mutational analyses suggest that the S1
      domains and a subsequent neck in the RNase-PH domain ring form an RNA entry pore
      to the processing chamber that only allows access of unstructured RNA. This
      structural framework can mechanistically unify observed features of exosomes,
      including processive degradation of unstructured RNA, the requirement for
      regulatory factors to degrade structured RNA, and left-over tails in rRNA
      trimming.

PMID- 16285928
TI  - Structural basis of 3' end RNA recognition and exoribonucleolytic cleavage by an
      exosome RNase PH core.
AB  - The exosome is a macromolecular complex that plays fundamental roles in the
      biogenesis and turnover of a large number of RNA species. Here we report the
      crystal structures of the Rrp41-Rrp42 core complex of the S. solfataricus exosome
      bound to short single-stranded RNAs and to ADP. The RNA binding cleft recognizes
      four nucleotides in a sequence-unspecific manner, mainly by electrostatic
      interactions with the phosphate groups. Interactions at the 2' hydroxyls of the
      sugars provide specificity for RNA over DNA. The structures show both the bound
      substrate and the cleaved product of the reaction, suggesting a catalytic
      mechanism for the 3'-5' phosphorolytic activity of the exosome.

PMID- 16285929
TI  - Antisense transcription and heterochromatin at the DM1 CTG repeats are
      constrained by CTCF.
AB  - Prior studies of the DM1 locus have shown that the CTG repeats are a component of
      a CTCF-dependent insulator element and that repeat expansion results in
      conversion of the region to heterochromatin. We now show that the DM1 insulator
      is maintained in a local heterochromatin context: an antisense transcript
      emanating from the adjacent SIX5 regulatory region extends into the insulator
      element and is converted into 21 nucleotide (nt) fragments with associated
      regional histone H3 lysine 9 (H3-K9) methylation and HP1gamma recruitment that is
      embedded within a region of euchromatin-associated H3 lysine 4 (H3-K4)
      methylation. CTCF restricts the extent of the antisense RNA at the wild-type (wt)
      DM1 locus and constrains the H3-K9 methylation to the nucleosome associated with
      the CTG repeat, whereas the expanded allele in congenital DM1 is associated with
      loss of CTCF binding, spread of heterochromatin, and regional CpG methylation.

PMID- 16285936
TI  - Not for the faint of heart.

PMID- 16285937
TI  - Image of the month. A gastric heterotopic pancreas with cystic change.

PMID- 16285938
TI  - Laminin-5 with transforming growth factor-beta1 induces epithelial to mesenchymal
      transition in hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: How hepatocellular carcinoma (HCC) cells acquire the ability
      to invade surrounding tissue is unknown, but epithelial mesenchymal transition
      (EMT) likely plays a role. We investigate how transforming growth factor (TGF)
      beta1 and extracellular matrix protein Laminin-5 (Ln-5) induce EMT and cancer
      invasion. METHODS: Snail, Slug, E-cadherin, beta-catenin and Ln-5 were
      investigated on HCC tissues and on HCC cell lines. RESULTS: We show that in HCC
      but not in peritumoral tissue of the same HCC patients, Ln-5, Snail, and Slug are
      up-regulated, E-cadherin is down-regulated and beta-catenin is translocated into
      the nuclei. In vitro, HCC "invasive" cells, partially EMT-transformed, show low
      levels of E-cadherin. In presence of Ln-5, Snail, and Slug are up-regulated, E
      cadherin is down-regulated, beta-catenin is translocated into the nuclei, and
      cells undergo a dramatic morphological change, becoming scattered and undergoing
      a complete EMT. This effect is reversed by anti-alpha3 but not by anti-alpha6
      integrin blocking antibody. HCC "noninvasive" cells are not EMT-transformed, and
      have constitutively high levels of E-cadherin. In presence of Ln-5, cells undergo
      partial EMT, Snail, and Slug are up-regulated, E-cadherin is down-regulated but
      cells do not scatter. However, the presence of both Ln-5 and TGF-beta1 completes
      the EMT process, beta-catenin is translocated into the nuclei, cells scatter and
      become invasive, recalling the "invasive" cells. In this case, too, the effect is
      reversed by anti-alpha3 integrin blocking antibody. CONCLUSIONS: Our study shows
      that Ln-5 and TGF-beta1 cooperatively induce EMT in HCC, suggesting the
      microenvironment as a potential target for new biological therapies.

PMID- 16285939
TI  - Trained registered nurses/endoscopy teams can administer propofol safely for
      endoscopy.
AB  - BACKGROUND & AIMS: Propofol has advantages as a sedative for endoscopic
      procedures. Its administration by anesthesia specialists is associated with high
      cost. Administration by nonanesthesiologists is controversial because of concerns
      about safety, particularly respiratory depression. METHODS: Three endoscopy units
      developed programs to train registered nurses supervised only by endoscopists in
      the administration of propofol for endoscopic procedures. The rate of adverse
      respiratory events was tracked from the inception of the programs. To estimate
      whether training nurses to give propofol on a widespread basis might be
      effective, we evaluated the individual safety records of all nurses and
      endoscopists involved in propofol delivery at the 3 centers. RESULTS: Among a
      total of 36,743 cases of nurse-administered propofol sedation (NAPS) at the 3
      centers, there were no cases requiring endotracheal intubation or resulting in
      death, neurologic sequelae, or other permanent injury. The rate of respiratory
      events requiring assisted ventilation was not significantly different among the 3
      centers and ranged from just <1 per 500 cases to just <1 per 1000 cases among the
      3 centers. There was no individual nurse or physician for whom the rate of
      respiratory events requiring assisted ventilation differed from the overall rate
      of events at the respective centers. CONCLUSIONS: Trained nurses and endoscopists
      can administer propofol safely for endoscopic procedures. Nurse-administered
      propofol sedation is one potential solution to the high cost associated with
      anesthetist-delivered sedation for endoscopy.

PMID- 16285940
TI  - MLH1 germline epimutations as a factor in hereditary nonpolyposis colorectal
      cancer.
AB  - BACKGROUND & AIMS: Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by
      heterozygous germline sequence mutations of DNA mismatch repair genes, most
      frequently MLH1 or MSH2. A novel molecular mechanism for HNPCC has recently been
      suggested by the finding of individuals with soma-wide monoallelic
      hypermethylation of the MLH1 gene promoter. In this study, we determined the
      frequency and role of germline epimutations of MLH1 in HNPCC. METHODS: A cohort
      of 160 probands from HNPCC families who did not harbor germline sequence
      mutations in the mismatch repair genes were screened for methylation of the MLH1
      and EPM2AIP1 promoters by combined bisulfite and restriction analyses. Allelic
      expression and family transmission of MLH1 were determined using polymorphisms in
      intron 4 and the 3' untranslated region. RESULTS: One of 160 individuals had
      monoallelic MLH1 hypermethylation in peripheral blood, hair follicles, and buccal
      mucosa, indicative of a soma-wide alteration. Monoallelic transcription of the
      paternal MLH1 allele was shown using a heterozygous expressed polymorphism within
      the 3' untranslated region. The hypermethylated allele was maternally
      transmitted, however, the mother and siblings who inherited the same maternal
      homologue were unmethylated at MLH1, suggesting the epimutation arose as a de
      novo event. CONCLUSIONS: Germline MLH1 epimutations are functionally equivalent
      to an inactivating mutation and produce a clinical phenotype that resembles
      HNPCC. Inheritance of epimutations is weak, so family history is not a useful
      guide for screening. Germline epimutations should be suspected in younger
      individuals without a family history who present with a microsatellite unstable
      tumor showing loss of MLH1 expression.

PMID- 16285941
TI  - Unexpected role of surface transglutaminase type II in celiac disease.
AB  - BACKGROUND & AIMS: In celiac disease (CD), transglutaminase type II (TG2) has 2
      fundamental roles: (1) as the autoantigen recognized by highly specific
      autoantibodies and (2) the modifier of pathogenic gliadin T-cell epitopes. It
      follows that inhibition of TG2 might represent an attractive strategy to curb the
      toxic action of gliadin. Here we studied the validity of this strategy using the
      organ culture approach. METHODS: Duodenal biopsy specimens from 30 treated
      patients with CD, 33 untreated patients with CD, and 24 controls were cultured
      with or without gliadin peptides p31-43, palpha-9, and deamidated palpha-9 for 20
      minutes, 3 hours, and 24 hours. In 31 patients with CD and 16 controls, TG2
      inhibitor R283 or anti-TG CUB 7402 or anti-surface TG2 (6B9) mAbs were used in
      cultures. T84 cells were also cultured with or without peptides with or without
      TG inhibitors. Mucosal modifications after culture were assessed by
      immunofluorescence, in situ detection of TG activity, confocal microscopy, and
      fluorescence-activated cell sorter analysis. RESULTS: The enzymatic inhibition of
      TG2 only controlled gliadin-specific T-cell activation. The binding of surface
      TG2 contained gliadin-specific T-cell activation and p31-43-induced actin
      rearrangement, epithelial phosphorylation, and apoptosis, both in organ cultures
      and T84 cells. CONCLUSIONS: These data indicate a novel and unexpected biological
      role for surface TG2 in the pathogenesis of CD suggesting a third role for TG2 in
      CD. These results have a specific impact for celiac disease, with wider
      implications indicating a novel biologic function of TG2 with possible
      repercussions in other diseases.

PMID- 16285942
TI  - Improved efficacy of 10-Day sequential treatment for Helicobacter pylori
      eradication in children: a randomized trial.
AB  - BACKGROUND & AIMS: The currently recommended first-line eradication treatment of
      Helicobacter pylori in children is usually successful in about 75%. Recently, in
      adults, a novel 10-day sequential treatment has achieved an eradication rate of
      95%. The aim of the study was to assess the H pylori eradication rate of the
      sequential treatment regimen compared with conventional triple therapy in
      children. METHODS: Seventy-eight consecutive children with H pylori infection
      were randomized to receive either sequential treatment (omeprazole plus
      amoxicillin for 5 days, followed by omeprazole plus clarithromycin plus
      tinidazole for another 5 days) (n = 38; 15 boys [39.5%]; median age, 11.0 years
      [range, 3.3-16 years]) or triple therapy (omeprazole, amoxicillin, and
      metronidazole) for 1 week (n = 37; 15 boys [40.5%]; median age, 9.9 years [range,
      4.3-16 years]). H pylori infection was based on 2 out of 3 positive tests
      results: 13C-urea breath test, rapid urease test, and histologic analysis.
      Eradication was assessed by 13C-urea breath test 8 weeks after therapy. RESULTS:
      Seventy-four patients completed the study. H pylori eradication was achieved in
      36 children receiving sequential treatment (97.3%; 95% confidence interval, 86.2
      99.5) and 28 children receiving triple therapy (75.7%; 95% confidence interval,
      59.8-86.7) (P < .02). Compliance with therapy was good (>95%) in all.
      CONCLUSIONS: Our study shows, for the first time in children, that 10-day
      sequential treatment achieves a higher eradication rate than standard triple
      therapy, which is consistent with the results of adult studies.

PMID- 16285943
TI  - Post-transcriptional regulation of Smad7 in the gut of patients with inflammatory
      bowel disease.
AB  - BACKGROUND & AIMS: Transforming growth factor (TGF)-beta1 is one of the most
      powerful endogenous negative regulators of inflammation. In patients with
      inflammatory bowel disease, despite abundant local TGF-beta1, there is a failure
      of TGF-beta-mediated negative regulation of nuclear factor kappaB activation and
      proinflammatory cytokine production because of increased intracellular expression
      of the endogenous inhibitor of TGF-beta1 signaling, Smad7. In this study, we
      examined the molecular mechanism underlying the induction of Smad7 in the human
      gut. METHODS: Whole intestinal mucosal and lamina propria mononuclear cell
      samples were analyzed for Smad7 by real-time polymerase chain reaction and
      Western blotting. Smad7 ubiquitination and acetylation, and interaction of Smad7
      with the intrinsic histone acetyltransferase, p300, were examined by
      immunoprecipitation and Western blotting. The effect of p300 silencing on Smad7
      expression was determined in Crohn's disease lamina propria mononuclear cells.
      RESULTS: We showed that Smad7 is not transcriptionally regulated in human gut but
      that its increase in patients with inflammatory bowel disease is due to
      posttranscriptional acetylation and stabilization by p300, which prevents Smad7
      ubiquitination and degradation in the proteasome. Hence, Smad7 protein in cells
      from normal gut is ubiquitinated and rapidly degraded. In contrast, in inflamed
      gut, Smad7 is acetylated and not ubiquitinated, is not degraded, and can be
      decreased by short interfering RNA to p300. CONCLUSIONS: These results identify
      posttranslational protein modification as of importance in chronic gut
      inflammation in humans.

PMID- 16285944
TI  - Effect of peptide YY3-36 on food intake in humans.
AB  - BACKGROUND & AIMS: Studies in animals and humans suggest a role for peptide YY
      (PYY3-36) in regulating satiety. The physiologic role of PYY3-36, however, has
      not been investigated in detail. METHODS: The present study was designed to
      examine PYY release in response to 2 meals differing in their calorie content and
      to relate the plasma levels to those obtained after exogenous infusion. In a
      second step, the effect of graded intravenous doses (0, 0.2, 0.4, and 0.8
      pmol.kg(-1).min(-1)) of synthetic human PYY3-36 on food intake was investigated
      in healthy male volunteers in a double-blind, placebo-controlled fashion.
      RESULTS: Plasma PYY concentrations increased in response to food intake
      reflecting the size of the calorie load. Graded PYY3-36 infusions resulted in a
      dose-dependent reduction in food intake (maximal inhibition, 35%; P < .001 vs
      control) and a similar reduction in calorie intake (32%; P < .001). Fluid
      ingestion was also reduced by PYY (18% reduction; P < .01). Nausea and fullness
      were the most common side effects produced by PYY, especially at the highest
      dose. Furthermore, subjects experienced less hunger and early fullness in the
      premeal period during PYY3-36 infusion at the highest dose (P < .05).
      CONCLUSIONS: This study shows that intravenous infusions of PYY3-36 decrease
      spontaneous food intake; the inhibition is, however, only significant at
      pharmacologic plasma concentrations. Whether PYY3-36 has a physiologic role in
      the regulation of satiety in humans remains to be defined.

PMID- 16285945
TI  - Influence of experimentally induced anxiety on gastric sensorimotor function in
      humans.
AB  - BACKGROUND & AIMS: Unexplained dyspeptic symptoms are associated with changes in
      gastric sensorimotor function and several psychopathologic dimensions, including
      anxiety. It is unclear whether this reflects common predisposition or a causal
      relationship. The aim of this study was to investigate whether experimentally
      induced anxiety would alter gastric sensorimotor function in health. METHODS:
      Fourteen subjects underwent a gastric barostat study to assess gastric
      sensitivity and accommodation. Eighteen subjects underwent a 10-minute satiety
      drinking test (30 mL/min) with registration of epigastric symptoms on a visual
      analogue scale (VAS) at 2-minute intervals. Emotional context was modulated for
      10 minutes at the start of each experiment by combined projection of validated
      facial expressions and an audiotape recalling a neutral or an anxious
      autobiographical experience. Anxiety levels were assessed using a VAS and the
      Spielberger State-Trait Anxiety Inventory (STAI). RESULTS: VAS and STAI scores
      confirmed efficacy of anxiety induction. During the anxiety condition, gastric
      compliance was significantly decreased (57 +/- 5 vs 40 +/- 5 mL/mm Hg; P < .01).
      Intraballoon pressures inducing discomfort during gastric distention were not
      altered, but the corresponding volume (630 +/- 47 vs 489 +/- 39 mL; P < .005) was
      significantly lower. Meal-induced relaxation was inhibited during the anxiety
      condition and this persisted for the 60-minute measurement (157 +/- 29 vs 100 +/-
      24 mL; P < .05). During the satiety drinking test, the anxiety condition was
      associated with significantly higher scores for satiety, fullness, and bloating.
      CONCLUSIONS: Experimentally induced anxiety alters gastric sensorimotor function,
      suggesting that psychological factors may play a causal role in the pathogenesis
      of some dyspeptic symptoms and mechanisms.

PMID- 16285947
TI  - Proteomic analysis of chronic pancreatitis and pancreatic adenocarcinoma.
AB  - BACKGROUND & AIMS: Markers to differentiate among pancreatic adenocarcinoma,
      chronic pancreatitis, and normal pancreas would be of significant clinical
      utility. This study was therefore designed to analyze the proteome of such
      specimens and identify new candidate proteins for differential diagnosis.
      METHODS: A PowerBlot analysis with more than 900 well-characterized antibodies
      was performed with tissue specimens from patients with chronic pancreatitis,
      pancreatic adenocarcinoma, and normal pancreas. Differential expression of
      selected proteins was confirmed on a larger scale by quantitative reverse
      transcription-polymerase chain reaction and immunohistochemistry using tissue
      arrays. RESULTS: A total of 30 and 102 proteins showed significant deregulation
      between normal pancreas when compared with chronic pancreatitis and pancreatic
      adenocarcinoma, respectively, and although a substantial proportion were found
      similarly dysregulated in both chronic pancreatitis and pancreatic
      adenocarcinoma, several proteins were identified as potential disease-specific
      markers. CONCLUSIONS: A large number of proteins are differentially expressed in
      chronic pancreatitis and pancreatic adenocarcinoma compared with normal pancreas.
      Among these, expression analysis of UHRF1, ATP7A, and aldehyde oxidase 1 in
      combination could potentially provide a useful additional diagnostic tool for
      fine-needle aspirated or cytological specimens obtained during endoscopic
      investigations.

PMID- 16285946
TI  - Bile acid synthesis in humans has a rapid diurnal variation that is asynchronous
      with cholesterol synthesis.
AB  - BACKGROUND & AIMS: The conversion of cholesterol to bile acids by the liver is an
      important regulator of body cholesterol homeostasis. In rodents, both cholesterol
      and bile acid synthesis have marked diurnal rhythms that peak synchronously at
      midnight. The aim of this study was to establish whether such diurnal rhythms are
      also present in healthy humans. METHODS: Serum levels of the markers 7alpha
      hydroxy-4-cholesten-3-one (C4) monitoring bile acid biosynthesis and lathosterol
      reflecting cholesterol synthesis were determined at 90-minute intervals in 8
      human volunteers during standardized dietary conditions. RESULTS: Serum C4 showed
      2 distinct peaks (2- to 4-fold above baseline) during a 24-hour period, the first
      at 1:00 pm and the second at 9:00 pm. During the night, C4 levels declined, and
      they returned to baseline levels the next morning. In contrast, serum lathosterol
      levels peaked at night, between midnight and 4:00 am. The diurnal changes of C4
      were not synchronous with serum lipid changes or with the postprandial increase
      in serum bile acids and were maintained in cholecystectomized subjects.
      CONCLUSIONS: Bile acid synthesis in humans has a diurnal rhythm, with 2 peaks
      during the daytime, that is opposite from the circadian rhythm of cholesterol
      synthesis. This is completely different from the pattern in rodents and indicates
      the presence of an important species variation in the regulation of cholesterol
      homeostasis.

PMID- 16285948
TI  - High-dose ursodeoxycholic acid in primary sclerosing cholangitis: a 5-year
      multicenter, randomized, controlled study.
AB  - BACKGROUND & AIMS: There is no medical treatment of proven benefit for primary
      sclerosing cholangitis. This study aimed at studying the effect of a higher dose
      of ursodeoxycholic acid than previously used on survival, symptoms, biochemistry,
      and quality of life in this disease. METHODS: A randomized placebo-controlled
      study was performed in tertiary and secondary gastroenterology units. A total of
      219 patients were randomized to 17 to 23 mg/kg body weight per day of
      ursodeoxycholic acid (n = 110) or placebo (n = 109) for 5 years. Follow-up data
      are available from 97 patients randomized to ursodeoxycholic acid and for 101
      randomized to placebo. Quality of life was assessed by using the Medical Outcomes
      Study 36-item Short-Form Health Survey. RESULTS: The combined end point "death or
      liver transplantation" occurred in 7 of 97 (7.2%) patients in the ursodeoxycholic
      acid group vs 11 of 101 (10.9%) patients in the placebo group (P = .368; 95%
      confidence interval, -12.2% to 4.7%). The occurrence of liver transplantation as
      a single end point showed a similar positive trend for ursodeoxycholic acid
      treatment (5/97 [5.2%] vs 8/101 [7.9%]; 95% confidence interval, -10.4% to 4.6%).
      Three ursodeoxycholic acid and 4 placebo patients died from cholangiocarcinoma,
      and 1 placebo patient died from liver failure. Alkaline phosphatase and alanine
      aminotransferase tended to decrease during the first 6 months. There were no
      differences between the 2 groups in symptoms or quality of life. Analyses of
      serum ursodeoxycholic acid concentration gave no evidence that noncompliance may
      have influenced the results. CONCLUSIONS: This study found no statistically
      significant beneficial effect of a higher dose of ursodeoxycholic acid than
      previously used on survival or prevention of cholangiocarcinoma in primary
      sclerosing cholangitis.

PMID- 16285949
TI  - Cdcs1, a major colitogenic locus in mice, regulates innate and adaptive immune
      response to enteric bacterial antigens.
AB  - BACKGROUND & AIMS: The absence of interleukin 10, a key cytokine in gut
      homeostasis, causes severe colitis in C3H/HeJBir but not C57BL/6J mice. The major
      modifier for colitis was mapped on chromosome 3 and designated cytokine
      deficiency-induced colitis susceptibility 1 (Cdcs1). We developed reciprocal
      Cdcs1 congenic stocks on both interleukin 10-deficient backgrounds to identify
      the susceptibility gene and its function. METHODS: C3H/HeJBir congenic for the
      C57BL/6J-derived Cdcs1 allele and reciprocal C57BL/6J congenic for the C3H/HeJBir
      allele were analyzed for colitis development. Parental strains were compared by
      electrophoretic mobility shift assay to assess the candidacy of nuclear factor
      kappaB p50 in the Cdcs1 interval. Functional differences were observed in innate
      and adaptive immune responses of parental and congenic stocks after bacterial
      ligand exposure in vitro (cytokine release from bone marrow-derived macrophage
      and dendritic cells) and in vivo (serum cytokines and primed CD4+ T cell
      proliferation). RESULTS: Cdcs1 was positioned within a minimum 7-megabase
      interval containing nuclear factor-kappaB p50. C3H/HeJBir colitis was
      significantly diminished by the C57BL/6J genome in this interval. Conversely,
      colitis in C57BL/6J was significantly exacerbated by the reciprocal C3H/HeJBir
      genome. C3H/HeJBir macrophages constitutively expressed higher nuclear factor
      kappaB p50. Functional assays showed that C3H/HeJBir showed reduced innate
      responsiveness both in vivo and in vitro to bacterial ligands but showed
      increased CD4 T-cell responses compared with C57BL/6J. This differential
      responsiveness was controlled by the respective allele at Cdcs1. CONCLUSIONS: The
      colitogenic Cdcs1 allele impairs innate immunity to bacterial products and in
      turn skews the adaptive immune response toward compensatory hyperresponsiveness
      and chronic intestinal inflammation.

PMID- 16285950
TI  - Macrophage migration inhibitory factor promotes intestinal tumorigenesis.
AB  - BACKGROUND & AIMS: The cytokine macrophage migration inhibitory factor (MIF) is
      expressed throughout the human gastrointestinal tract. Recently, protumorigenic
      activity of MIF has been described in several cancer models. Therefore, we
      investigated the expression and function of MIF during the early stages of
      intestinal tumorigenesis. METHODS: MIF messenger RNA, protein, and tautomerase
      activity were measured in normal intestinal mucosa and adenomas from patients
      with sporadic colorectal adenomas and in the adenomatous polyposis coli
      (Apc)Min/+ mouse model of intestinal tumorigenesis. MIF function was investigated
      by using VACO-235 human colorectal adenoma cells in vitro and by testing the
      effect of genetic deletion of Mif on ApcMin/+ mouse intestinal tumorigenesis.
      RESULTS: MIF expression and tautomerase activity were increased in human and
      ApcMin/+ mouse intestinal adenomas compared with adjacent normal mucosa. Up
      regulation of MIF occurred mainly in epithelial cells (associated with an
      increasing grade of dysplasia), but also in stromal plasma cells. Exogenous MIF
      inhibited apoptosis and promoted anchorage-independent growth of VACO-235 cells
      (maximal at 100 ng/mL). Homozygous deletion of Mif was associated with a
      reduction in the number and size of ApcMin/+ mouse adenomas (P = .025 for the
      difference in large [>7-mm] tumors) and decreased angiogenesis (43% decrease in
      mean tumor microvessel density), but there was no alteration in epithelial cell
      apoptosis or proliferation. CONCLUSIONS: MIF expression is increased in sporadic
      human colorectal adenomas, and exogenous MIF drives tumorigenic behavior of
      epithelial cells in vitro. Mif also promotes intestinal tumorigenesis
      (predominantly via angiogenesis) in the ApcMin/+ mouse. Therefore, MIF is a
      potential colorectal cancer chemoprevention target.

PMID- 16285951
TI  - Melastatin-type transient receptor potential channel 7 is required for intestinal
      pacemaking activity.
AB  - BACKGROUND & AIMS: Interstitial cells of Cajal are pacemakers in the
      gastrointestinal tract, regulating rhythmicity by activating nonselective cation
      channels. In Caenorhabditis elegans, the melastatin-type transient receptor
      potential (TRPM) channel, especially TRPM7, was suggested as being involved in
      defecation rhythm. The aim here was to show that the nonselective cation channel
      in interstitial cells of Cajal in mouse small intestine has properties
      essentially identical to those of murine TRPM7, heterologously expressed in human
      embryonic kidney cells. METHODS: The patch-clamp technique for whole-cell
      recording was used in cultured or single interstitial cells of Cajal. TRPM7
      specific small interfering RNAs were used for specific inhibition of TRPM7.
      RESULTS: Electrophysiological and pharmacological properties of the nonselective
      cation channel in interstitial cells of Cajal were the same as those of TRPM7.
      Reverse-transcription polymerase chain reaction, Western blotting, and
      immunohistochemistry all showed abundant and localized expression of TRPM7
      messenger RNA and protein in mouse small intestine. Treatment of primary cultured
      interstitial cells of Cajal with TRPM7-specific small interfering RNA resulted in
      inhibition of pacemaking activity. CONCLUSIONS: TRPM7 is required for intestinal
      pacemaking. The protein is a likely potential target for pharmacological
      treatment of motor disorders of the gut.

PMID- 16285952
TI  - Negative transcriptional regulation of human colonic smooth muscle Cav1.2
      channels by p50 and p65 subunits of nuclear factor-kappaB.
AB  - BACKGROUND & AIMS: The expression of Cav1.2 channels in colonic circular smooth
      muscle cells and the contractility of these cells are suppressed in inflammation.
      Our aim was to investigate whether the activation of p50 and p65 nuclear factor
      kappaB subunits mediates these effects. METHODS: Primary cultures of human
      colonic circular smooth muscle cells and muscle strips were used. RESULTS: The
      messenger RNA and protein expression of the pore-forming alpha1C subunit of
      Cav1.2 channels decreased time dependently in response to tumor necrosis factor
      alpha. This effect was blocked by prior transient transfection of the cells with
      antisense oligonucleotides to p50 or p65. The overexpression of p50 and p65
      inhibited the constitutive expression of alpha1C. Three putative kappaB binding
      motifs were identified on the 5' flanking region of exon 1b of the human L-type
      calcium channel alpha1C gene. Progressive 5' deletions of the promoter and point
      mutations of the kappaB binding motifs indicated that the two 5' binding sites,
      but not the third 3' binding site, were essential for the suppression of alpha1C.
      Transient transfection of human colonic circular muscle strips with antisense
      oligonucleotides to p50 and p65 decreased expression of the 2 nuclear factor
      kappaB units and reversed the suppression of alpha1C, as well as that of the
      contractile response to acetylcholine, by 24 hours of treatment with tumor
      necrosis factor alpha. CONCLUSIONS: The activation of p50 and p65 by tumor
      necrosis factor alpha suppresses the expression of the alpha1C subunit of Cav1.2
      channels in human colonic circular smooth muscle cells and their contractile
      response to acetylcholine. Nuclear factor-kappaB must bind concurrently to the
      two 5' kappaB motifs on the promoter of alpha1C to produce this effect.

PMID- 16285953
TI  - Corticotropin-releasing hormone receptor 1 antagonist blocks brain-gut activation
      induced by colonic distention in rats.
AB  - BACKGROUND & AIMS: The corticotropin-releasing hormone receptor 1 mediates stress
      induced changes in colonic motor activity and emotion. We tested the hypothesis
      that pretreatment with JTC-017, a specific corticotropin-releasing hormone
      receptor 1 antagonist, blocks colorectal distention-induced hippocampal
      noradrenaline release and visceral perception in rats. We also investigated
      whether pretreatment with JTC-017 blocks acute or chronic colorectal distention
      induced adrenocorticotropic hormone release, anxiety, and stress-induced changes
      in colonic motility. METHODS: Rats were pretreated intrahippocampally with alpha
      helical corticotropin-releasing hormone (1.25 microg/kg; vehicle), a nonspecific
      corticotropin-releasing hormone receptor antagonist, or intraperitoneally with
      JTC-017 (10 mg/kg). Hippocampal noradrenaline release after microdialysis and the
      frequency of abdominal contractions were measured in response to acute colorectal
      distention. Plasma adrenocorticotropic hormone levels, anxiety-related behavior,
      and stress-induced changes in colonic motility were evaluated after acute or
      chronic colorectal distention followed by exposure to an elevated plus maze.
      RESULTS: Administration of alpha-helical corticotropin-releasing hormone or JTC
      017 significantly attenuated hippocampal noradrenaline release and reduced the
      frequency of abdominal contractions induced by acute distention. In addition, JTC
      017 significantly reduced plasma adrenocorticotropic hormone and anxiety after
      acute distention. After chronic distention, changes in plasma adrenocorticotropic
      hormone and anxiety were not significant because of habituation. In contrast, a
      significant increase in fecal pellet output during the elevated plus maze was
      observed after chronic distention. This increase in fecal pellet output was
      blocked by pretreatment with JTC-017. CONCLUSIONS: Our results suggest that JTC
      017, a specific corticotropin-releasing hormone receptor 1 antagonist, attenuates
      hippocampal noradrenaline release, visceral perception, adrenocorticotropic
      hormone release, and anxiety after acute colorectal distention in rats. In
      addition, JTC-017 blocks stress-induced changes in colonic motility after chronic
      colorectal distention in rats.

PMID- 16285954
TI  - p27kip1 deficiency confers susceptibility to gastric carcinogenesis in
      Helicobacter pylori-infected mice.
AB  - BACKGROUND & AIMS: Determining how Helicobacter pylori promotes gastric cancer
      and whether H pylori eradication decreases cancer risk would be helped by
      suitable murine models. Mice lacking the cyclin-dependent kinase inhibitor
      p27kip1 are susceptible to carcinogen-induced tumors. Furthermore, p27 stimulates
      gastric epithelial apoptosis and inhibits proliferation, expression is decreased
      by H pylori, and low levels are associated with a poor prognosis in gastric
      cancer. We therefore evaluated p27-deficient mice as a model for H pylori
      associated gastric cancer. METHODS: Wild-type and p27-/- C57BL/6 mice were
      infected with H pylori mouse-adapted Sydney strain at 6-8 weeks of age and 6-10
      mice of each type were euthanized 15, 30, 45, 60, and 75 weeks later. RESULTS:
      Uninfected p27-/- mice developed gastric hyperplasia. H pylori-infected p27-/-
      mice frequently developed intestinal metaplasia (40% at 30 weeks, 67% at 45
      weeks), and after 60 weeks 7 of 12 mice developed significant dysplasia and
      gastric cancer, recapitulating human intestinal-type gastric carcinogenesis. Wild
      type mice developed intestinal metaplasia only after 75 weeks of infection;
      significant gastric dysplasia was observed in 1 animal (P < .05 for each
      comparison with p27-/- mice). No disease developed in uninfected mice. H pylori
      infection in p27-/- mice was associated with significantly decreased apoptosis
      and increased epithelial proliferation, inflammation, and H pylori density
      compared with infection in wild-type mice. CONCLUSIONS: p27 loss and H pylori
      colonization cooperate to produce gastric cancer. The p27-deficient mouse affords
      opportunities to examine the pathogenesis of H pylori in gastric carcinogenesis
      and to test eradication and chemopreventive strategies.

PMID- 16285955
TI  - 5-HT7 receptors modulate peristalsis and accommodation in the guinea pig ileum.
AB  - BACKGROUND & AIMS: The 5-hydroxytryptamine 7 (5-HT7) receptors mediate intestinal
      smooth muscle relaxation. In this study, we evaluated the expression of 5-HT7
      receptors in the guinea pig ileum and their role in peristalsis and accommodation
      of the circular muscle. METHODS: We used immunohistochemistry and confocal
      microscopy with whole tissue and cultured myenteric neurons. Peristalsis was
      induced by delivering a solution into the oral end of an isolated ileal segment.
      The effect of the selective 5-HT7 receptor antagonist SB-269970 (100 nmol/L) on
      peristaltic activity was evaluated at 30, 60, and 90 minutes and compared with
      control. RESULTS: 5-HT7 receptor immunoreactivity was localized to numerous
      myenteric neurons, a few submucosal neurons, and a few smooth muscle cells of the
      ileum. In enteric cultured neurons, 5-HT7 receptor immunoreactivity was observed
      in subpopulations of after hyperpolarizing neurons and descending neurons as
      identified by neuron-specific nuclear protein or calbindin and neuronal nitric
      oxide synthase or vasoactive intestinal peptide antibodies, respectively. SB
      269970 significantly increased the threshold pressure by 33.3% +/- 2.2% (P <
      .001) and by 27.2% +/- 1.6% (P < .05) at 60 and 90 minutes, respectively, without
      modifying the threshold volume. The accommodation significantly decreased by
      27.5% both at 60 and 90 minutes (P < .05). CONCLUSIONS: Our results indicate that
      endogenous 5-HT is involved in the modulation of circular muscle accommodation
      during the preparatory phase of peristalsis via the activation of 5-HT7 receptors
      expressed by neurons in addition to smooth muscle cells. Overstimulation of these
      receptors leading to an exaggerated accommodation of circular muscle might
      contribute to abdominal symptoms in functional bowel disorders.

PMID- 16285956
TI  - Isolation and characterization of a putative intestinal stem cell fraction from
      mouse jejunum.
AB  - BACKGROUND & AIMS: Although there have been many recent advances regarding the
      biology of intestinal stem cells, the field has been hampered significantly by
      the lack of a method to isolate these cells. Therefore, the aim of this study was
      to explore the hypothesis that viable intestinal stem cells can be isolated as a
      side population (SP) by fluorescence-activated cell sorting after staining with
      the DNA-binding dye Hoechst 33342. METHODS: Preparations of individual cells from
      either whole mucosa or epithelium of mouse jejunum were stained with Hoechst
      33342 and propidium iodide and then sorted using fluorescence-activated cell
      sorting. Cells were characterized using fluorochrome-labeled antibodies to
      surface markers, intracellular markers, and annexin V to detect early apoptosis.
      Total RNA was isolated from sorted fractions and used for quantitative real-time
      reverse-transcription polymerase chain reaction to evaluate the expression of
      cell lineage markers and the intestinal stem-cell marker, Musashi-1. RESULTS:
      Adult and neonatal jejunum contain a viable population of cells that shows the SP
      phenotype and is sensitive to verapamil. This population of cells (from both
      mucosal and epithelial preparations) includes a CD45-negative fraction
      corresponding to nonhematopoietic cells, which shows minimal expression of
      surface markers typically found on stem cells from other tissues and of
      intracellular markers found in mesenchymal cells. Additionally, these cells were
      enriched for Musashi-1 and beta1-integrin, were cytokeratin positive, and
      survived in culture for up to 14 days. CONCLUSIONS: The CD45-negative SP
      fraction, although not pure, represents the successful isolation of a viable
      population significantly enriched in small intestinal epithelial stem cells.

PMID- 16285957
TI  - Galectin-3 modulates MUC2 mucin expression in human colon cancer cells at the
      level of transcription via AP-1 activation.
AB  - BACKGROUND & AIMS: Galectin-3 and MUC2 intestinal mucin each have been correlated
      with the malignant behavior of colon cancer cells. Galectin-3 modulates
      expression of MUC2 protein, but the specific regulatory mechanisms are unknown.
      This study sought to determine how galectin-3 increases MUC2 expression. METHODS:
      Galectin-3 levels in human colon cancer cells of high and low metastatic ability
      were manipulated via expression of galectin-3 complementary DNA in sense or
      antisense orientation. Galectin-3 and MUC2 protein expression were determined by
      Western analysis and immunocytochemistry. Transient transfections of promoter
      reporter constructs were used to monitor MUC2 transcription and AP-1 activity.
      Electrophoretic mobility shift assays, site-directed mutagenesis, and chromatin
      immunoprecipitation were used to monitor the participation of AP-1 in MUC2
      transcription. RESULTS: Alterations in galectin-3 levels correlated with both
      MUC2 protein expression and transcription. By using MUC2 promoter constructs of
      different lengths, galectin-3 responsiveness was found between 1500 and 2186 bp
      upstream of the translation start site, a region that contains 1 consensus AP-1
      binding site. AP-1 activity paralleled MUC2 transcription in the different cell
      lines. Mutation in the AP-1 site markedly decreased MUC2 promoter activity, and
      MUC2 transcription was inhibited by cotransfection with a dominant-negative AP-1
      vector. Electrophoretic mobility shift assays, co-immunoprecipitation, and
      chromatin immunoprecipitation analyses suggested an association between galectin
      3, c-Jun, and Fra-1 in forming a complex at the AP-1 site on the MUC2 promoter.
      CONCLUSIONS: Galectin-3 up-regulation of MUC2 transcription occurs at the level
      of transcription through AP-1 activation. This may have important implications
      for understanding the role of galectin-3 and MUC2 in colon cancer metastasis.

PMID- 16285958
TI  - Smoothelin-a is essential for functional intestinal smooth muscle contractility
      in mice.
AB  - BACKGROUND & AIMS: In patients with chronic intestinal pseudo-obstruction,
      intestinal motility is disturbed by either nervous or myogenic aberrations. The
      cause of the myogenic form is unknown, but it is likely to originate in the
      contractile apparatus of the smooth muscle cells. Smoothelins are actin-binding
      proteins that are expressed abundantly in visceral (smoothelin-A) and vascular
      (smoothelin-B) smooth muscle. Experimental data indicate a role for smoothelins
      in smooth muscle contraction. A smoothelin-deficient mouse model may help to
      establish the role of smoothelin-A in intestinal contraction and provide a model
      for myogenic chronic intestinal pseudo-obstruction. METHODS: We used gene
      targeting to investigate the function of smoothelin-A in intestinal tissues. By
      deletion of exons 18, 19, and 20 from the smoothelin gene, the expression of both
      smoothelin isoforms was disrupted. The effects of the deficiency were evaluated
      by pathologic and physiologic analyses. RESULTS: In smoothelin-A/B knockout mice,
      the intestine was fragile and less flexible compared with wild-type littermates.
      The circular and longitudinal muscle layers of the intestine were hypertrophic.
      Deficiency of smoothelin-A led to irregular slow wave patterns and impaired
      contraction of intestinal smooth muscle, leading to hampered transport in vivo.
      This caused obstructions that provoked intestinal diverticulosis and occasionally
      intestinal rupture. CONCLUSIONS: Smoothelin-A is essential for functional
      contractility of intestinal smooth muscle. Hampered intestinal transit in
      smoothelin-A/B knockout mice causes obstruction, starvation, and, ultimately,
      premature death. The pathology of mice lacking smoothelin-A is reminiscent of
      that seen in patients with chronic intestinal pseudo-obstruction.

PMID- 16285959
TI  - Silencing of caspase-8 in murine hepatocellular carcinomas is mediated via
      methylation of an essential promoter element.
AB  - BACKGROUND & AIMS: Caspase-8 is the apical caspase essential for triggering Fas
      induced apoptosis. In this study, we investigated caspase-8 expression in
      hepatocellular carcinomas (HCCs) using recently described HCC mouse models (c-myc
      and IgEGF transgenes). METHODS: HCCs were isolated from c-myc and IgEGF
      transgenic animals. Expression of caspase-8 was monitored by reverse
      transcription polymerase chain reaction. The murine caspase-8 promoter was
      characterized by luciferase-reporter analysis and the analysis of promoter
      methylation was performed by bisulfite genomic sequencing. RESULTS: In HCCs
      investigated, we frequently found a lack of caspase-8 messenger RNA expression.
      Genomic deletions at the caspase-8 locus did not contribute to caspase-8
      silencing. We examined tumor-derived promoter sequences and found significant
      hypermethylation at distinct CpG sites. In parallel, we characterized the murine
      caspase-8 promoter and identified a 30-bp promoter element that is indispensable
      for basal promoter activity. This minimal promoter element contained SP1 binding
      motifs that are colocalized with CpG sites and were methylated in tumor-derived
      promoter sequences. Electrophoretic mobility shift assay analysis showed that
      methylation of these SP1 sites is sufficient to prevent SP1 complex formation. To
      support our data, we mimicked the methylation pattern of a tumor-derived caspase
      8 promoter in vitro using CpG methylase and found a strong reduction of promoter
      activity. CONCLUSIONS: We show that HCCs are correlated frequently with silencing
      of caspase-8 expression and provide data suggesting that caspase-8 silencing is a
      direct consequence of inhibiting SP1-dependent transactivation caused by CpG
      methylation at its essential binding sites in the promoter region. Our data
      support the hypothesis that inhibition of apoptosis triggers
      hepatocarcinogenesis.

PMID- 16285961
TI  - Expression and role of Gas6 protein and of its receptor Axl in hepatic
      regeneration from oval cells in the rat.
AB  - BACKGROUND & AIMS: The growth arrest-specific gene 6 (Gas6) protein is a vitamin
      K-dependent protein that binds to the Axl subfamily of tyrosine kinase receptors
      and exerts antiapoptotic and proliferative effects. Because Gas6 plays a role in
      development and tissue remodelling, we studied its expression as well as that of
      its high-affinity receptor Axl in a well-characterized model of hepatic
      regeneration from precursor oval cells. METHODS: Hepatic regeneration was induced
      by treating rats with acetylaminofluorene followed by partial hepatectomy.
      RESULTS: Oval cell accumulation, which predominated in periportal regions,
      reached a maximum at days 9 and 14 after hepatectomy and declined thereafter.
      Oval cells expressed Gas6 protein and messenger RNA (mRNA). Axl mRNA hepatic
      levels paralleled the number of oval cells, and immunohistochemistry showed Axl
      expression in these cells. WB-F344 cells, a hepatocytic precursor cell line, also
      expressed Gas6 and Axl. Addition of Gas6 significantly increased the number of WB
      F344 cells cultured with or without serum. Gas6 did not increase cell entry in
      the S phase of the cell cycle but inhibited 15-d-prostaglandin J2-induced WB-F344
      cell apoptosis. CONCLUSIONS: Our data demonstrate an expression of Gas6 and of
      its receptor Axl by oval cells during hepatic regeneration. Because the Gas6/Axl
      couple protects from apoptosis a hepatocytic precursor cell line, these results
      strongly suggest that the Gas6/Axl couple favors oval cell accumulation in
      regenerating liver by an autocrine/paracrine mechanism.

PMID- 16285960
TI  - STAT3 NH2-terminal acetylation is activated by the hepatic acute-phase response
      and required for IL-6 induction of angiotensinogen.
AB  - BACKGROUND & AIMS: The signal transducers and activators of transcription (STATs)
      are cytoplasmic transcription factors mediating acute-phase response (APR) of the
      human angiotensinogen (hAGT) gene in hepatocytes. The mechanisms of how STAT3
      activates target genes are unknown. Here we analyzed the biochemistry of STAT3
      activation by interleukin (IL)-6 in hepatocellular carcinoma HepG2 and Balb/C
      mice. METHODS: Immunoprecipitation-Western assays and Matrix Assisted Laser
      Desorption-Time of Flight mass spectrometry determined sites of STAT3 acetylation
      by the 300-kilodalton target of E1A (p300) co-activator. The subcellular
      localization of acetylation-deficient STAT3 molecules were studied by microscopic
      imaging, effects on DNA binding measured by gel shift and chromatin
      immunoprecipitation (ChIP) assays, and gene transactivation by Northern blot and
      reporter assays. RESULTS: Two Lys residues at amino acids 49 and 87 in the STAT3
      NH2 terminus are acetylated by p300. Lys-to-Arg point mutations (STAT3 K49R/K87R)
      had no effect on inducible DNA binding, but blocked p300-mediated acetyl(Ac)
      STAT3 formation and abrogated IL-6-induced hAGT activation. Although STAT3
      K49R/K87R rapidly translocated into the nucleus, it did not bind p300 and had
      delayed cytoplasmic redistribution. ChIP assays show IL-6-inducible acetylated
      STAT3 and p300 binding to the native hAGT promoter. Activation of the APR in mice
      induces nuclear Tyr phosphorylated and acetylated STAT3 in hepatic nuclei. We
      also observed that STAT3 interacts with histone deacetylases (HDACs),
      specifically HDAC 1, that down-regulate IL-6-induced hAGT transactivation.
      CONCLUSIONS: IL-6-induced target gene activation requires p300-mediated STAT3
      acetylation, and HDACs are involved in the termination of STAT3 action. These
      studies indicate the acetylation-deacetylation reaction as a novel signaling
      mechanism controlling the IL-6-STAT3 pathway in the hepatic APR.

PMID- 16285962
TI  - Integrin and extracellular matrix interactions regulate engraftment of
      transplanted hepatocytes in the rat liver.
AB  - BACKGROUND & AIMS: Recognition and circumvention of the hepatic endothelial
      barrier is critical in the engraftment of transplanted cells. We examined whether
      interactions between integrin and extracellular matrix component receptors could
      be manipulated for improving transplanted cell engraftment and liver
      repopulation. METHODS: Fischer 344 rat hepatocytes were transplanted into
      syngeneic dipeptidyl peptidase IV-deficient rats. Coating of cells or of liver
      sinusoids with natural collagen, natural laminin, or an engineered fibronectin
      like polymer was studied with analysis of cell engraftment and liver repopulation
      using histologic and molecular assays. Focal adhesion complexes were identified
      by vinculin immunostaining. The role of integrin receptors in cell engraftment
      was analyzed with RGD peptide inhibition assays. RESULTS: Coating of cells with
      extracellular matrix components before transplantation did not enhance cell
      engraftment. In contrast, intraportal infusion of collagen or fibronectin-like
      polymer in recipients prior to cell transplantation increased cell engraftment.
      Adherence of transplanted cells to the hepatic endothelium resulted in rapid
      activation of vinculin-containing focal adhesion complexes. Superior cell
      engraftment in animals treated with fibronectin-like polymer was RGD sensitive,
      verifying the integrin-dependent nature of this process. Moreover, studies in the
      retrorsine-partial hepatectomy rat model showed that intraportal infusion of the
      fibronectin-like polymer before cell transplantation significantly accelerated
      liver repopulation. CONCLUSIONS: Integrin-extracellular matrix component
      interactions can be manipulated for enhancing cell engraftment in the liver. Such
      mechanisms will be relevant for engraftment of other cell types and for
      strategies concerning liver-directed cell therapy.

PMID- 16285963
TI  - Short hairpin RNA modulates transforming growth factor beta signaling in life
      threatening liver failure in mice.
AB  - BACKGROUND & AIMS: Transforming growth factor beta (TGF-beta) receptor II (TGF
      betaRII), which is essential for TGF-beta signaling and is involved in the
      causation or participates in the pathway of various human disorders, is
      consequently considered a key target for therapeutics and analysis of the
      pathophysiology associated with disruption of the TGF-beta system. In the liver,
      TGF-beta plays an essential role in hepatocyte apoptosis, growth inhibition, and
      progression of fibrogenesis. There is a critical need to introduce technology
      involving the TGF-beta system, such as RNA interference (RNAi), which has high
      potential for in vivo therapeutics and analytical activities. METHODS: Here, we
      investigated the effect of short hairpin RNA targeting TGF-betaRII, using
      hepatocyte injury in human and mouse cell lines and liver injury mouse models.
      RESULTS: We demonstrated that short hairpin RNA targeting TGF-betaRII can be used
      to silence TGF-betaRII genes in mouse and human cell lines, and physiologic and
      morphologic changes in hepatocytes suffering from acute injury are spared by RNAi
      mediated gene silencing of the target gene and by suppressing downstream signal
      transduction. Furthermore, short hairpin RNA targeting TGF-betaRII protected mice
      from life-threatening acute liver failure. CONCLUSIONS: Our study suggests the
      potential use of TGF-betaRII silencing by RNAi as an analytical tool for TGF-beta
      signaling and gene-specific therapy in human disorders.

PMID- 16285964
TI  - NF-kappaB activation, rather than TNF, mediates hepatic inflammation in a murine
      dietary model of steatohepatitis.
AB  - BACKGROUND & AIMS: We explored the roles of nuclear factor-kappaB (NF-kappaB) and
      tumor necrosis factor (TNF) alpha (TNF-alpha) as mediators of inflammation in a
      nutritional model of steatohepatitis. METHODS: Wild-type (wt), TNF null -/-, and
      TNF receptor (R)-1-/- mice were fed a methionine- and choline-deficient (MCD)
      diet for up to 5 weeks. Liver injury (serum alanine aminotransferase [ALT]),
      hepatic inflammation, triglycerides, and lipid peroxide levels were determined.
      Hepatic NF-kappaB activation and expression of TNF and intercellular adhesion
      molecule-1 (ICAM-1) were assayed. RESULTS: Irrespective of genotype, MCD diet-fed
      mice developed hepatic lipid peroxidation and serum ALT elevation; at day 10,
      livers from wt, TNF-/-, and TNFR-1-/- mice showed equivalent steatohepatitis. NF
      kappaB/DNA binding was enhanced in hepatic nuclear fractions from MCD diet-fed wt
      mice compared with dietary controls; there were corresponding increases of ICAM-1
      and TNF messenger RNA (mRNA). Likewise, NF-kappaB activation and ICAM-1
      expression were enhanced by MCD dietary feeding in TNF-/- and TNFR-1-/- mice
      compared with respective controls. To establish whether NF-kappaB is a primary
      mediator of inflammation in experimental steatohepatitis, we over-expressed a
      mutant, nondegradable IkappaB (mIkappaB), delivered by adenovirus in vivo. As
      expected, hepatic mIkappaB expression reduced NF-kappaB/DNA binding induced by
      MCD dietary feeding, with resultant abrogation of ICAM-1 and TNF synthesis. Such
      blockade of NF-kappaB transcriptional activation substantially protected against
      development of steatohepatitis, with significant reductions in liver injury and
      hepatic inflammation. CONCLUSIONS: In the MCD dietary model of steatohepatitis,
      NF-kappaB is activated early and is an important proinflammatory mediator of
      lesion development, but steatohepatitis occurs independently of TNF synthesis and
      TNFR-1 activation.

PMID- 16285965
TI  - Hydrogen peroxide reduces lower esophageal sphincter tone in human esophagitis.
AB  - BACKGROUND & AIMS: We have previously used the normal lower esophageal sphincter
      (N-LES) of human organ donors to examine the physiologic signal transduction of
      lower esophageal sphincter (LES) circular muscle. Now, for the first time, we
      have obtained a human LES specimen with esophagitis (E-LES) and characterized its
      pathophysiologic mechanical and inflammatory profiles. METHODS: E-LES was
      examined histologically, and its in vitro circular muscle contraction and
      production of inflammatory mediators were compared with those of N-LES. RESULTS:
      E-LES exhibited scattered erosions and displayed inflammatory cells in the
      epithelial layer, basal zone hyperplasia, and elongation of lamina propria
      papillae, characteristic of chronic reflux esophagitis. E-LES muscle strips
      developed lower in vitro tone (0.78 g) than N-LES (3.3 +/- 0.2 g). E-LES tone was
      essentially restored to normal by the H2O2 scavenger catalase, suggesting that
      H2O2 was responsible for reduction of tone. NOX5 cDNA was higher and H2O2 levels
      were 4 times higher in E-LES circular muscle (0.85 nmol/mg protein) than in N-LES
      (0.19 +/- 0.05 nmol/mg protein). When N-LES smooth muscle was incubated in H2O2
      (70 micromol/L, 2 hours), platelet activating factor (PAF), prostaglandin E2
      (PGE2), and F2-isoprostane increased 2.5, 5.2, and 36 times, respectively. In E
      LES, levels of PAF, PGE2, and F2-isoprostane were 4, 6, and 40 times,
      respectively, higher than in N-LES. PAF, PGE2, and F2 isoprostane produced dose
      dependent reductions in tone of N-LES muscle strips. CONCLUSIONS: We conclude
      that an excessive production of H2O2 triggers an increased production of PAF,
      PGE2, and F2-isoprostane, which are responsible for reducing LES tone in human
      esophagitis.

PMID- 16285966
TI  - Microarray analysis of endothelial differentially expressed genes in liver of
      cirrhotic rats.
AB  - BACKGROUND & AIMS: There is a long-standing interest in the identification of
      endothelial-specific pathways for therapeutic targeting in cirrhosis. Therefore,
      the aim of this study was to evaluate differences in gene expression patterns
      between liver endothelial cells (LECs) from control and cirrhotic rats by using
      microarrays. METHODS: LECs were obtained by isopycnic centrifugation. LECs gene
      expression was then analyzed on high-density oligonucleotide microarrays.
      RESULTS: Analysis of gene expression revealed that most of the differentially
      expressed mRNA in cirrhosis are associated with extracellular matrix remodeling,
      inflammation, antioxidant/stress response, and cell signaling. CONCLUSIONS: The
      collective expression changes observed within some functional groups of genes
      indicate that LECs in cirrhotic livers may contribute to lymphangiogenesis,
      enhancement of fibrogenesis and inflammatory processes, changes in cell-cell
      interaction with up-regulation of adherens junction proteins, and alterations in
      the intrahepatic vascular tone because of the down-regulation of genes involved
      in vasodilatation.

PMID- 16285967
TI  - The hedgehog signalling pathway in the gastrointestinal tract: implications for
      development, homeostasis, and disease.
AB  - The hedgehog signalling pathway is critical to normal mammalian gastrointestinal
      development. Through epithelial-mesenchymal interactions, hedgehog signalling
      ensures appropriate axial patterning of the embryonic gut. Congenital
      abnormalities, including malrotations, anorectal malformations, and
      tracheoesophageal fistula are associated with germ-line mutations/deletion of
      genes encoding hedgehog signalling components in man and present in genetically
      engineered animal models. In adults, there is evidence that the pathway plays a
      role in maintaining stem cell populations in the stomach and directing epithelial
      cell differentiation in the intestine. Recent data implicate hedgehog signalling
      in the formation and maintenance of a number of malignancies, including those of
      the upper gastrointestinal (GI) tract and pancreas, in which abrogation of the
      pathway offers a novel therapeutic approach in animal models. Most recently,
      evidence in vitro indicates that there is a recapitulation of embryonic hedgehog
      signalling in acute epithelial injury and chronic inflammation, a finding with
      key implications for inflammatory disorders of the intestine, such as
      inflammatory bowel diseases. This pathway may provide an important link between
      chronic inflammation and cancer. We summarize the available evidence
      demonstrating that this developmental pathway has continuing roles in adult
      homeostasis and is dysregulated in malignancy and inflammation of the
      gastrointestinal tract.

PMID- 16285969
TI  - American Gastroenterological Association future trends committee report: the
      application of genomic and proteomic technologies to digestive disease diagnosis
      and treatment and their likely impact on gastroenterology clinical practice.

PMID- 16285968
TI  - Management of nonsteroidal, anti-inflammatory, drug-associated dyspepsia.

PMID- 16285970
TI  - American Gastroenterological Association medical position statement: evaluation
      of dyspepsia.

PMID- 16285971
TI  - American gastroenterological association technical review on the evaluation of
      dyspepsia.

PMID- 16285972
TI  - Nurse-assisted propofol sedation: the jury is in!

PMID- 16285973
TI  - Of mice and men: what to learn about human inflammatory bowel disease from
      genetic analysis of murine inflammation.

PMID- 16285974
TI  - MIFed about cancer?

PMID- 16285975
TI  - Deciphering the molecular basis for the pacemaker signal.

PMID- 16285976
TI  - Caspase-8, death-receptor signaling, and hepatocarcinogenesis: the Fas and the
      furious.

PMID- 16285977
TI  - Colonoscopy is superior to flexible sigmoidoscopy for colorectal cancer
      screening: now beyond a reasonable doubt?

PMID- 16285978
TI  - Swimming in cloudy waters: efforts to prevent HCV-related HCC.

PMID- 16285979
TI  - Alcohol and cigarettes: partners in crime in chronic pancreatitis.

PMID- 16285980
TI  - Screening for hemochromatosis: yes, but whom and how?

PMID- 16285984
TI  - Evaluation of microarray analysis for predicting treatment responsiveness in
      patients with chronic hepatitis C viral infection.

PMID- 16285985
TI  - Explaining divergent results of meta-analyses on proton pump inhibitor treatment
      for ulcer bleeding.

PMID- 16285986
TI  - Mannose-binding lectin and liver transplantation.

PMID- 16285987
TI  - The natural history of NAFLD: impressively unimpressive.

PMID- 16285989
TI  - Staging gastritis: an international proposal.

PMID- 16285990
TI  - Apolipoprotein A-I and the molecular variant apoA-I(Milano): evaluation of the
      antiatherogenic effects in knock-in mouse model.
AB  - No evidence of premature vascular disease is found in apolipoprotein A-I(Milano)
      (apoA-I(M)) human carriers, despite very low high density lipoprotein (HDL)
      cholesterol levels. Whether apoA-I(M) may impart a "gain of function" in
      atherosclerosis protection compared to wild-type apoA-I is hotly debated. To
      address this question, knock-in mice expressing human apoA-I or apoA-I(M) were
      crossed with atherosclerosis-susceptible mice expressing the human apoB/A-II
      transgene (h-B/A-II/A-I(Hu/Hu) and h-B/A-II/A-I(M)(Hu/Hu)). On a chow diet, h-B/A
      II/A-I(M)(Hu/Hu) mice were characterized by low HDL cholesterol levels compared
      to h-B/A-II/A-I(Hu/Hu) mice (35.65+/-8.00 mg/dl versus 58.09+/-13.50mg/dl,
      respectively; p<0.005). Gender differences in response to high fat diet were
      observed in both h-B/A-II/A-I(M)(Hu/Hu) and h-B/A-II/A-I(Hu/Hu) lines. h-B/A-II/A
      I(M)(Hu/Hu) females had higher total cholesterol levels compared to h-B/A-II/A
      I(Hu/Hu) females (895.08+/-183.07 mg/dl versus 544.43+/-116.42 mg/dl; p<0.05) and
      developed larger atherosclerotic lesions (148,260+/-78,924 microm(2) versus
      54,132+/-43,204 microm(2), respectively; p<0.05). On the contrary, no difference
      in mean lesion area was found between h-B/A-II/A-I(M)(Hu/Hu) and h-B/A-II/A
      I(Hu/Hu) males (19,779+/-6,098 microm(2) versus 15,706+/-13,095 microm(2);
      p=0.685). Our data suggest that, in the atherosclerosis-susceptible human apoB/A
      II mouse model, expression of the human apoA-I(M) gene does not have protective
      advantage over that of the apoA-I gene.

PMID- 16285991
TI  - The effects of S-allylmercaptocaptopril, the synthetic product of allicin and
      captopril, on cardiovascular risk factors associated with the metabolic syndrome.
AB  - Pure allicin, prepared biosynthetically by reacting synthetic alliin with an
      immobilized alliinase enzyme, is known to possess cardioprotective effects.
      However, in its pure form, allicin is pharmacologically unstable. S
      allylmercaptocaptopril (CPSSA) is a new stable synthetic compound produced by
      chemical reaction between allicin and the angiotensin converting enzyme inhibitor
      captopril. Using the fructose-induced metabolic syndrome rat model we studied the
      effects of short-term treatment with two doses of CPSSA on cardiovascular risk
      factors associated with the metabolic syndrome, in comparison to the effects of
      allicin and captopril separately. Allicin (8 mg/(kg day)) significantly reduced
      insulin, triglycerides, and homocysteine concentrations, and had a slight effect
      on SBP. Captopril (50mg/(kg day)) only improved blood pressure and homocysteine.
      Treatment with low dose of CPSSA (5mg/(kg day)) lowered SBP but did not improve
      any other measured parameter, while treatment with a higher dose (50mg/(kg day))
      significantly decreased blood pressure, triglycerides, and homocysteine
      concentrations. We conclude that the combined molecule CPSSA integrates the anti
      hypertensive, lipid-lowering, and homocysteine-reducing effects of both allicin
      and captopril, making it a potential cardiovascular protective agent.

PMID- 16285992
TI  - Intermittent high glucose enhances ICAM-1, VCAM-1 and E-selectin expression in
      human umbilical vein endothelial cells in culture: the distinct role of protein
      kinase C and mitochondrial superoxide production.
AB  - In this study the effects of stable and intermittent high glucose concentrations
      on ICAM-1, VCAM-1 and E-selectin production, PKC activity and PKCbetaI, betaII
      and delta isoforms expression in cultured HUVEC have been examined. In stable
      high glucose ICAM-1, VCAM-1 and E-selectin concentration and mRNA expression
      increased, and this effect was even more evident in intermittent high glucose.
      PKC activity increased in fluctuating glucose compared to stable high glucose,
      due to an over-expression of betaI, betaII and delta isoforms. ICAM-1, VCAM-1 and
      E-selectin, after the adding of total PKC inhibitor bisindolylmaleimide-I (BIMI
      I) and LY379196, a specific inhibitor of PKCbeta, were equally reduced. 8
      Hydroxydeoxyguanosine (8-OHdG), a sensitive indicator of oxidative damage to DNA,
      increased in stable and even more in intermittent high glucose and was reduced by
      both BIMI-I and LY379196. However, when thenoyltrifluoroacetone (TTFA), an
      inhibitor of mitochondrial complex II and the SOD mimetic Mn(III)tetrakis(4
      benzoic acid) porphyrin chloride (MnTBAP) were added, all adhesion molecules, any
      PKC isoforms expression and 8-hydroxydeoxyguanosine were normalized in both
      constant and oscillating glucose. In conclusion intermittent high glucose induces
      a greater expression of the adhesion molecules than stable high glucose; this
      effect seems to be related to an activation of PKCbeta, but completely dependent
      from mitochondrial free radicals over-production.

PMID- 16285993
TI  - Plasma MCP-1 level and risk for peripheral arterial disease and incident coronary
      heart disease: Atherosclerosis Risk in Communities study.
AB  - Monocyte chemoattractant protein-1 (MCP-1), which mediates the recruitment of
      monocytes, has been suggested to play a role in atherosclerosis. Because the
      correlation between circulating MCP-1 and cardiovascular risk has not been
      thoroughly investigated, we determined the relationship between MCP-1 level and
      peripheral arterial disease (PAD) or coronary heart disease (CHD). In the
      Atherosclerosis Risk in Communities (ARIC) study, 209 cases with lower extremity
      PAD and 412 cases with incident CHD were compared with 733 and 709 subjects
      without PAD and CHD, respectively. Mean plasma MCP-1 levels were significantly
      higher in PAD cases (468.7 versus 416.5 pg/mL in non-cases). MCP-1 levels
      correlated significantly with other inflammatory markers in comparison subjects.
      Logistic regression analyses showed a significant association of MCP-1 with PAD,
      independent of traditional CHD risk factors, with an odds ratio of 2.14 (95% CI,
      1.28-3.60) for the highest MCP-1 tertile compared with the lowest. Incident CHD
      risk increased significantly per 1 standard deviation (S.D.) difference in MCP-1
      level independent of other cardiovascular risk factors, including inflammatory
      markers. These data show that MCP-1 is associated with atherosclerotic disease in
      two vascular beds and suggest that MCP-1 may be a novel target for
      atherosclerosis therapy.

PMID- 16285994
TI  - The implication of obesity and central fat on markers of chronic inflammation:
      The ATTICA study.
AB  - OBJECTIVE: We evaluated the association of obesity with various markers of
      chronic inflammation, in a population-based sample of 3,042 adults. METHODS:
      During 2001-2002, we randomly enrolled 1,514 men (18-87 years old) and 1,528
      women (18-89 years old), from the Attica area, Greece; the sampling was
      stratified by the age-sex distribution of the region (census 2001). Among several
      variables, we also measured various inflammatory markers (C-reactive protein,
      tumor necrosis factor alpha, amyloid A, white blood cells and interleukin-6) and
      anthropometric variables (weight, height, waist and hip circumferences). Central
      fat was defined as waist-to-hip ratio>or=0.95 in men and>or=0.8 in women, while
      obesity as body mass index (BMI)>29.9 kg/m(2). RESULTS: Central fat prevailed in
      36% of men and 43% of women (p<0.001), while obesity prevailed in 20% of men and
      15% of women, respectively. Compared to participants with normal body fat
      distribution, those with central fat exhibited 53% higher C-reactive protein
      levels, 30% higher tumor necrosis factor, alpha levels, 26% higher amyloid A
      levels, 17% higher white blood cell counts and 42% higher interleukin-6 levels
      (all p<0.05). We observed that all inflammation markers were related to BMI
      (index for obesity), waist and to waist-to-hip ratio (indices for central fat),
      in both genders. Moreover, the models that included waist or waist-to-hip ratio
      as independent variable had higher explanatory ability (i.e. R(2)) than the
      models included BMI, especially in women, even after adjusting for age and
      various other potential confounders. CONCLUSION: Our results suggest a
      relationship between central adiposity and inflammation process, irrespective of
      age and other potential confounders. This association was more prominent than the
      relationship between total obesity and inflammation. It could be hypothesized
      that a disproportionate accumulation of visceral fat mass could be partially
      associated with increased coronary risk, through inflammation process.

PMID- 16285995
TI  - 3'UTR/T polymorphism of lectin-like oxidized low-density lipoprotein receptor-1
      (LOX-1) is associated with modified anti-platelet activity of atorvastatin in
      hypercholesterolemic subjects.
AB  - Oxidized-low density lipoproteins (ox-LDL) and the specific receptor LOX-1 are
      involved in atherogenesis and atherothrombosis. LOX-1 downregulation is
      associated with the anti-platelet action of atorvastatin. 3'UTR/T LOX-1
      polymorphism has been associated with increased risk of coronary artery disease.
      This study was planned to determine whether LOX-1 genetic variations could affect
      anti-platelet action of atorvastatin. We studied by platelet P-selectin (P-sel),
      CD36 and LOX-1 expression (cytofluorimetric detection) whether differences in
      cellular activation could be suitable in 109 3'UTR/T carriers out of 201
      hypercholesterolemic subjects treated with atorvastatin 20mg/day. Hyperactivated
      platelets (P-sel in resting cells and % variation upon thrombin activation,
      p<0.001) were detected at baseline in patients without significant differences
      between T or C carriers. P-sel and platelet-associated ox-LDL, were significantly
      decreased (all p<0.001) in C carriers after one week of treatment before LDL
      reduction. In 3'UTR/T carriers P-sel was reduced (p<0.01) after 6 weeks of
      treatment according to LDL and ox-LDL reduction. In 3'UTR/T carriers atorvastatin
      reduced platelet activity by LDL and ox-LDL lowering and not by rapid CD36 and
      LOX-1 downregulation as in C carriers. Such data suggest that in T carriers LDL
      lowering is needed to achieve anti-platelet action.

PMID- 16285996
TI  - Inhibition of thromboxane biosynthesis by triflusal in type 2 diabetes mellitus.
AB  - Triflusal is an antiplatelet drug related to aspirin, with different
      pharmacological properties and a lower haemorrhagic risk. We aimed at comparing
      their effects on platelet and endothelial activation in type 2 diabetes mellitus
      (T2DM). In a randomized, double-blind, parallel group study, we compared the
      effects of three daily regimens (300, 600, and 900 mg) of triflusal, and aspirin
      (100mg/day) on urinary 11-dehydro-thromboxane (TX)B(2), index of in vivo platelet
      activation, ex vivo platelet function using the analyzer PFA-100, plasma von
      Willebrand factor (vWF), P-selectin, intercellular adhesion molecule-1 (ICAM-1),
      vascular cell adhesion molecule-1 (VCAM-1), and serum nitrite and nitrate (NO(2)(
      )+NO(3)(-)) in 60 T2DM patients. Triflusal induced a dose-dependent reduction in
      11-dehydro-TXB(2) and a prolongation of closure time in the presence of collagen
      plus epinephrine (Coll/Epi-CT). The effects of the highest triflusal dose were
      not different from those of aspirin. The closure time in the presence of collagen
      plus ADP (Coll/ADP-CT), ICAM-1, VCAM-1, and NO(2)(-)+NO(3)(-) were not modified
      either by triflusal or aspirin. Plasma P-selectin and vWF were reduced by
      triflusal but not by aspirin. In T2DM triflusal causes a profound inhibition of
      platelet TXA(2) biosynthesis in vivo, acting on different targets involved in the
      platelet-endothelial cell interactions.

PMID- 16285997
TI  - The peroxisome proliferator-activated receptor delta +294T/C polymorphism in
      relation to lipoprotein metabolism in patients with diabetes mellitus type 2 and
      in non-diabetic controls.
AB  - OBJECTIVE: Peroxisome proliferator-activated receptor delta (PPARdelta) is an
      ubiquitously expressed transcription factor that has been implicated in the
      regulation of genes related to cholesterol metabolism. Conflicting results exist
      regarding the association of the recently described +294T/C polymorphism in the
      5'-untranslated region (5'-UTR) in exon 4 of the PPARdelta gene and plasma
      lipoprotein concentrations. Purpose of the present study was to examine for the
      first time in a German population and for the first time also in women the
      presence of a potential association between the aforementioned polymorphism and
      lipoprotein concentrations in patients with diabetes mellitus type 2 (DM-2) and
      in non-diabetic controls. Furthermore, a possible gene-gene interaction between
      the PPARdelta +294T/C polymorphism and the PPARalpha L162V polymorphism was
      examined. DESIGN AND METHODS: We determined by PCR the polymorphism in a total of
      402 patients with DM-2 (230 men and 172 women) and in 436 healthy controls (248
      men and 188 women) from the LIANCO study (lipid analytic cologne). RESULTS: The
      genotype distribution was not different between DM-2 and controls (+294TT 65.6%
      versus 66.7%, +294TC 30.5% versus 29.4%, +294CC 3.9 versus 4.0%, respectively).
      There was no difference in the low density lipoprotein cholesterol (LDL-C), high
      density lipoprotein cholesterol (HDL-C) or triglyceride (TG) concentrations
      between carriers and non-carriers of the rare C allele in the DM-2 population. In
      specific, the heterozygotes for the C allele had LDL-C concentrations of 157+/-80
      mg/dl, HDL-C of 54+/-17 mg/dl and TG of 273+/-507 mg/dl, while the C allele
      homozygotes had concentrations of LDL-C 149+/-44 mg/dl, HDL-C of 59+/-21 mg/dl
      and TG of 197+/-110 mg/dl. The LDL-C, HDL-C and TG concentrations of TT
      homozygotes were 156+/-49 mg/dl, 56+/-18 mg/dl and TG 225+/-242 mg/dl,
      respectively. The same lack of association was present in the non-diabetic
      controls, both in men and in women. There was no association between the
      genotypes and body mass index. Furthermore, no gene-gene interaction between the
      PPARdelta +294TC and the PPARalpha L162V polymorphism was observed regarding
      lipoprotein concentrations and atherosclerotic disease. CONCLUSIONS: The data
      suggest that the PPARdelta +294T/C polymorphism has no influence on plasma
      lipoprotein concentrations, body mass index or atherosclerotic disease either in
      healthy subjects or in patients with DM-2, both in males and females.

PMID- 16285998
TI  - Elevated leptin levels in subjects with familial combined hyperlipidemia are
      associated with the increased risk for CVD.
AB  - Familial combined hyperlipidemia (FCH) is characterized by hypercholesterolemia
      and/or hypertriglyceridemia and is associated with premature cardiovascular
      disease (CVD). Other features of FCH are obesity and insulin resistance. Serum
      leptin levels have been associated with obesity, insulin resistance and CVD. The
      aim of this study was to determine whether increased leptin levels contribute to
      the FCH phenotype and its increased risk for CVD. The study population comprised
      644 subjects, including 158 FCH patients. Leptin levels were determined, using a
      commercially available ELISA. For both males and females, the mean leptin level
      (ng/ml) was higher in FCH patients compared to normolipidemic relatives and
      spouses. However, after standardization for BMI and insulin resistance, these
      differences disappeared. The 90th percentile of the leptin level, standardized
      for BMI, insulin resistance and gender, was associated with an increased risk for
      CVD in FCH patients (odds ratio=2.9, 95% CI=1.1-8.0) and in non-FCH subjects
      (odds ratio=3.4, 95% CI=1.3-9.0). The overall increased risk for CVD, associated
      with a leptin level >90th percentile, was 3.3 (95% CI=1.7-6.4). We conclude that
      in patients with FCH, leptin levels are increased in proportion to their higher
      BMI and the presence of insulin resistance. These increased leptin levels are
      associated with an increased risk for CVD both in FCH patients and non-FCH
      subjects, independent of BMI, insulin resistance and gender.

PMID- 16285999
TI  - Inter-study reproducibility of 3D volume selective fast spin echo sequence for
      quantifying carotid artery wall volume in asymptomatic subjects.
AB  - PURPOSE: To determine, in asymptomatic subjects, the inter-study reproducibility
      of a three-dimensional (3D) volume selective fast spin echo (FSE) cardiovascular
      magnetic resonance sequence for the assessment of carotid artery wall volume as a
      measure of atheroma burden. METHODS: Inter-study reproducibility was evaluated in
      16 asymptomatic volunteers (10 male, 6 female). Both carotid arteries were
      scanned twice with a median inter-scan time of 5 days. The images were acquired
      in cross-section, and the total carotid arterial wall volume (TWV) was calculated
      by subtraction of the total carotid lumen volume from the total outer carotid
      vessel volume. RESULTS: The mean carotid T1-weighted TWV for the first and second
      scans was 828 and 821 mm(3), respectively (mean difference 7 mm(3), p=0.45). The
      standard deviation (S.D.) of the differences between the measurements was 38
      mm(3) yielding an inter-study coefficient of variation of 4.6%. The time for each
      study was approximately 30 min. For the longitudinal evaluation of carotid
      atheroma burden with pharmacological intervention versus placebo, 32 subjects
      would enable a difference of 38 mm(3) to be detected with a significance level of
      5% with 80% power. CONCLUSION: Volumetric analysis with carotid CMR in
      asymptomatic subjects using a 3D volume-selective FSE is time-efficient with good
      inter-study reproducibility, and is well suited for longitudinal studies of
      carotid atheroma with reasonable sample sizes.

PMID- 16286000
TI  - Robert Koch: the grandfather of cloning?
AB  - This year marks the centenary of Robert Koch's Nobel Prize for discovering the
      cause of tuberculosis. Koch was also the first scientist to isolate the anthrax
      and cholera microbes. Yet perhaps one of his greatest contributions to biology is
      the least appreciated: his method for propagating individual colonies of bacteria
      on plates, a technique that came to be called cloning.

PMID- 16286001
TI  - RNAi: RISC gets loaded.
AB  - When an siRNA or miRNA proceeds through the RNA-induced silencing complex
      assembly pathway, only one of the two approximately 21-nucleotide RNA strands
      survives in the final, active complex. In this issue of Cell, Matranga et al.
      (2005) and Rand et al. (2005) reveal the fate of the rejected passenger siRNA
      strand. Additionally, Gregory et al. (2005) define a heterotrimeric complex from
      humans that appears to execute dsRNA loading, strand selection, and target mRNA
      cleavage activities.

PMID- 16286003
TI  - The enigmatic role of Sir2 in aging.
AB  - In this issue of Cell, Longo and colleagues (Fabrizio et al., 2005) examine the
      role of Sir2, a histone deacetylase, in chronological aging in yeast by measuring
      the long-term survival of nondividing cells. In contrast to measurements of aging
      for mitotic cells, cell survival in the nonmitotic state is decreased by Sir2
      activity under conditions that mimic calorie restriction.

PMID- 16286002
TI  - Slugging it out: fine tuning the p53-PUMA death connection.
AB  - In response to DNA damage, the tumor suppressor p53 elicits a complex cellular
      response. In this issue of Cell, Wu et al. (2005) show that the transcription
      factor SLUG is induced by p53 and protects hematopoietic progenitor cells from
      apoptosis triggered by DNA damage. SLUG exerts this protective role by repressing
      Puma, a proapoptotic target of p53. PUMA is also a key coordinator of apoptosis
      mediated by both nuclear and cytoplasmic functions of p53 (Chi-puk et al., 2005).

PMID- 16286004
TI  - A nose by any other name (should smell as sweetly).
AB  - The standard view that the control of mating behavior by pheromones is mediated
      by the vomeronasal organ, and not by the main olfactory epithelium, has recently
      been called into question. In this issue of Cell, two independent studies (Boehm
      et al., 2005; Yoon et al., 2005) examine the inputs from each of these olfactory
      pathways to a population of neurons that plays a central role in mating behavior.

PMID- 16286005
TI  - Identification of two proteins required for conjunction and regular segregation
      of achiasmate homologs in Drosophila male meiosis.
AB  - In Drosophila males, homologous chromosomes segregate by an unusual process
      involving physical connections not dependent on recombination. We have identified
      two meiotic proteins specifically required for this process. Stromalin in Meiosis
      (SNM) is a divergent member of the SCC3/SA/STAG family of cohesin proteins, and
      Modifier of Mdg4 in Meiosis (MNM) is one of many BTB-domain proteins expressed
      from the mod(mdg4) locus. SNM and MNM colocalize along with a repetitive rDNA
      sequence known to function as an X-Y pairing site to nucleolar foci during
      meiotic prophase and to a compact structure associated with the X-Y bivalent
      during prometaphase I and metaphase I. Additionally, MNM localizes to autosomal
      foci throughout meiosis I. These proteins are mutually dependent for their
      colocalization, and at least MNM requires the function of teflon, another meiotic
      gene. SNM and MNM do not colocalize with SMC1, suggesting that the homolog
      conjunction mechanism is independent of cohesin.

PMID- 16286006
TI  - mTOR and S6K1 mediate assembly of the translation preinitiation complex through
      dynamic protein interchange and ordered phosphorylation events.
AB  - In response to nutrients, energy sufficiency, hormones, and mitogenic agents,
      S6K1 phosphorylates several targets linked to translation. However, the molecular
      mechanisms whereby S6K1 is activated, encounters substrate, and contributes to
      translation initiation are poorly understood. We show that mTOR and S6K1 maneuver
      on and off the eukaryotic initiation factor 3 (eIF3) translation initiation
      complex in a signal-dependent, choreographed fashion. When inactive, S6K1
      associates with the eIF3 complex, while the S6K1 activator mTOR/raptor does not.
      Cell stimulation promotes mTOR/raptor binding to the eIF3 complex and
      phosphorylation of S6K1 at its hydrophobic motif. Phosphorylation results in S6K1
      dissociation, activation, and subsequent phosphorylation of its translational
      targets, including eIF4B, which is then recruited into the complex in a
      phosphorylation-dependent manner. Thus, the eIF3 preinitiation complex acts as a
      scaffold to coordinate a dynamic sequence of events in response to stimuli that
      promote efficient protein synthesis.

PMID- 16286007
TI  - Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S
      to suppress spurious intragenic transcription.
AB  - Yeast Rpd3 histone deacetylase plays an important role at actively transcribed
      genes. We characterized two distinct Rpd3 complexes, Rpd3L and Rpd3S, by MudPIT
      analysis. Both complexes shared a three subunit core and Rpd3L contains unique
      subunits consistent with being a promoter targeted corepressor. Rco1 and Eaf3
      were subunits specific to Rpd3S. Mutants of RCO1 and EAF3 exhibited increased
      acetylation in the FLO8 and STE11 open reading frames (ORFs) and the appearance
      of aberrant transcripts initiating within the body of these ORFs. Mutants in the
      RNA polymerase II-associated SET2 histone methyltransferase also displayed these
      defects. Set2 functioned upstream of Rpd3S and the Eaf3 methyl-histone binding
      chromodomain was important for recruitment of Rpd3S and for deacetylation within
      the STE11 ORF. These data indicate that Pol II-associated Set2 methylates H3
      providing a transcriptional memory which signals for deacetylation of ORFs by
      Rpd3S. This erases transcription elongation-associated acetylation to suppress
      intragenic transcription initiation.

PMID- 16286008
TI  - Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive
      Rpd3 complex.
AB  - The yeast histone deacetylase Rpd3 can be recruited to promoters to repress
      transcription initiation. Biochemical, genetic, and gene-expression analyses show
      that Rpd3 exists in two distinct complexes. The smaller complex, Rpd3C(S), shares
      Sin3 and Ume1 with Rpd3C(L) but contains the unique subunits Rco1 and Eaf3.
      Rpd3C(S) mutants exhibit phenotypes remarkably similar to those of Set2, a
      histone methyltransferase associated with elongating RNA polymerase II. Chromatin
      immunoprecipitation and biochemical experiments indicate that the chromodomain of
      Eaf3 recruits Rpd3C(S) to nucleosomes methylated by Set2 on histone H3 lysine 36,
      leading to deacetylation of transcribed regions. This pathway apparently acts to
      negatively regulate transcription because deleting the genes for Set2 or Rpd3C(S)
      bypasses the requirement for the positive elongation factor Bur1/Bur2.

PMID- 16286009
TI  - Slug antagonizes p53-mediated apoptosis of hematopoietic progenitors by
      repressing puma.
AB  - In response to DNA damage, the p53 tumor suppressor can elicit either apoptosis
      or cell-cycle arrest and repair, but how this critical decision is made in
      specific cell types remains largely undefined. We investigated the mechanism by
      which the transcriptional repressor Slug specifically rescues hematopoietic
      progenitor cells from lethal doses of gamma radiation. We show that Slug is
      transcriptionally induced by p53 upon irradiation and then protects the damaged
      cell from apoptosis by directly repressing p53-mediated transcription of puma, a
      key BH3-only antagonist of the antiapoptotic Bcl-2 proteins. We established the
      physiologic significance of Slug-mediated repression of puma by demonstrating
      that mice deficient in both genes survive doses of total-body irradiation that
      lethally deplete hematopoietic progenitor populations in mice lacking only slug.
      Thus, Slug functions downstream of p53 in developing blood cells as a critical
      switch that prevents their apoptosis by antagonizing the trans-activation of puma
      by p53.

PMID- 16286010
TI  - Sir2 blocks extreme life-span extension.
AB  - Sir2 is a conserved deacetylase that modulates life span in yeast, worms, and
      flies and stress response in mammals. In yeast, Sir2 is required for maintaining
      replicative life span, and increasing Sir2 dosage can delay replicative aging. We
      address the role of Sir2 in regulating chronological life span in yeast. Lack of
      Sir2 along with calorie restriction and/or mutations in the yeast AKT homolog,
      Sch9, or Ras pathways causes a dramatic chronological life-span extension.
      Inactivation of Sir2 causes uptake and catabolism of ethanol and upregulation of
      many stress-resistance and sporulation genes. These changes while sufficient to
      extend chronological life span in wild-type yeast require severe calorie
      restriction or additional mutations to extend life span of sir2Delta mutants. Our
      results demonstrate that effects of SIR2 on chronological life span are opposite
      to replicatve life span and suggest that the relevant activities of Sir2-like
      deacetylases may also be complex in higher eukaryotes.

PMID- 16286011
TI  - stathmin, a gene enriched in the amygdala, controls both learned and innate fear.
AB  - Little is known about the molecular mechanisms of learned and innate fear. We
      have identified stathmin, an inhibitor of microtubule formation, as highly
      expressed in the lateral nucleus (LA) of the amygdala as well as in the thalamic
      and cortical structures that send information to the LA about the conditioned
      (learned fear) and unconditioned stimuli (innate fear). Whole-cell recordings
      from amygdala slices that are isolated from stathmin knockout mice show deficits
      in spike-timing-dependent long-term potentiation (LTP). The knockout mice also
      exhibit decreased memory in amygdala-dependent fear conditioning and fail to
      recognize danger in innately aversive environments. By contrast, these mice do
      not show deficits in the water maze, a spatial task dependent on the hippocampus,
      where stathmin is not normally expressed. We therefore conclude that stathmin is
      required for the induction of LTP in afferent inputs to the amygdala and is
      essential in regulating both innate and learned fear.

PMID- 16286013
TI  - An IL-1 family member requires caspase-1 processing and signals through the ST2
      receptor.
AB  - Activation of ST2, an orphan member of the IL-1 receptor family for 16 years,
      drives T helper type 2 (T(H)2) responses. The cytokine IL-33 is the specific
      ligand for ST2. IL-33 recapitulates much of the existing data that ST2 promotes
      T(H)2-type responses. The caspase-1 processing of precursor IL-33 provides a
      therapeutic target to control allergic diseases.

PMID- 16286014
TI  - Critical role of ITIM-bearing FcgammaR on DCs in the capture and presentation of
      native antigen to B cells.
AB  - The contribution of dendritic cells (DCs) to antibody responses through antigen
      unspecific B cell costimulation is well documented. now demonstrate that the ITIM
      bearing FcgammaRIIB allows DCs to recycle internalized native antigen (Ag) for
      presentation to B cells, a process that might be critical for the initiation of
      humoral responses.

PMID- 16286015
TI  - Human TLR-7-, -8-, and -9-mediated induction of IFN-alpha/beta and -lambda Is
      IRAK-4 dependent and redundant for protective immunity to viruses.
AB  - Five TLRs are thought to play an important role in antiviral immunity, sensing
      viral products and inducing IFN-alpha/beta and -lambda. Surprisingly, patients
      with a defect of IRAK-4, a critical kinase downstream from TLRs, are resistant to
      common viruses. We show here that IFN-alpha/beta and -lambda induction via TLR-7,
      TLR-8, and TLR-9 was abolished in IRAK-4-deficient blood cells. In contrast, IFN
      alpha/beta and -lambda were induced normally by TLR-3 and TLR-4 agonists.
      Moreover, IFN-beta and -lambda were normally induced by TLR-3 agonists and
      viruses in IRAK-4-deficient fibroblasts. We further show that IFN-alpha/beta and 
      lambda production in response to 9 of 11 viruses tested was normal or weakly
      affected in IRAK-4-deficient blood cells. Thus, IRAK-4-deficient patients may
      control viral infections by TLR-3- and TLR-4-dependent and/or TLR-independent
      production of IFNs. The TLR-7-, TLR-8-, and TLR-9-dependent induction of IFN
      alpha/beta and -lambda is strictly IRAK-4 dependent and paradoxically redundant
      for protective immunity to most viruses in humans.

PMID- 16286016
TI  - IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related
      protein ST2 and induces T helper type 2-associated cytokines.
AB  - Cytokines of the interleukin-1 (IL-1) family, such as IL-1 alpha/beta and IL-18,
      have important functions in host defense, immune regulation, and inflammation.
      Insight into their biological functions has led to novel therapeutic approaches
      to treat human inflammatory diseases. Within the IL-1 family, IL-1 alpha/beta, IL
      1Ra, and IL-18 have been matched to their respective receptor complexes and have
      been shown to have distinct biological functions. The most prominent orphan IL-1
      receptor is ST 2. This receptor has been described as a negative regulator of
      Toll-like receptor-IL-1 receptor signaling, but it also functions as an important
      effector molecule of T helper type 2 responses. We report a member of the IL-1
      family, IL-33, which mediates its biological effects via IL-1 receptor ST 2,
      activates NF-kappaB and MAP kinases, and drives production of T(H)2-associated
      cytokines from in vitro polarized T(H)2 cells. In vivo, IL-33 induces the
      expression of IL-4, IL-5, and IL-13 and leads to severe pathological changes in
      mucosal organs.

PMID- 16286017
TI  - IL-6-STAT3 controls intracellular MHC class II alphabeta dimer level through
      cathepsin S activity in dendritic cells.
AB  - We found IL-6-STAT3 pathway suppresses MHC class II (MHCII) expression on
      dendritic cells (DCs) and attenuates T cell activation. Here, we showed that IL-6
      STAT3 signaling reduced intracellular MHCII alphabeta dimmer, Ii, and H2-DM
      levels in DCs. IL-6-mediated STAT3 activation decreased cystatin C level, an
      endogenous inhibitor of cathepsins, and enhanced cathepsin activities.
      Importantly, cathepsin S inhibitors blocked reduction of MHCII alphabeta dimer,
      Ii, and H2-DM in the IL-6-treated DCs. Overexpression of cystatin C suppressed IL
      6-STAT3-mediated increase of cathepsin S activity and reduction of MHCII
      alphabeta dimer, Ii, and H2-DM levels in DCs. Cathepsin S overexpression in DCs
      decreased intracellular MHCII alphabeta dimer, Ii, and H2-DM levels, LPS-mediated
      surface expression of MHCII and suppressed CD4(+) T cell activation. IL-6-gp130
      STAT3 signaling in vivo decreased cystatin C expression and MHCII alphabeta dimer
      level in DCs. Thus, IL-6-STAT3-mediated increase of cathepsin S activity reduces
      the MHCII alphabeta dimer, Ii, and H2-DM levels in DCs, and suppresses CD4(+) T
      cell-mediated immune responses.

PMID- 16286018
TI  - Cell surface recycling of internalized antigen permits dendritic cell priming of
      B cells.
AB  - Dendritic cells process internalized antigens to present degradative products on
      MHC for TCR recognition. Because antigen-exposed DCs also induce humoral
      immunity, DCs must also retain antigen in its native state for the engagement of
      BCR on B cells. Here, we demonstrate that antigen endocytosed by the inhibitory
      Fc receptor, FcgammaRIIB, accesses a non-degradative intracellular vesicular
      compartment that recycles to the cell surface, enabling interaction of native
      antigen with BCR on B cells. Immunization with IgG-opsonized, T independent
      antigens leads to enhanced humoral responses in a FcgammaRIIB and complement
      dependent manner. IC-loaded DCs trafficking to the splenic marginal zone can
      prime a T independent response in an FcgammaRIIB-dependent manner. Thus dendritic
      cells are equipped with both non-degradative and degradative antigen uptake
      pathways to facilitate antigen presentation to both B and T cells.

PMID- 16286019
TI  - Sensory neurons regulate the effector functions of CD8+ T cells in controlling
      HSV-1 latency ex vivo.
AB  - We provide evidence that sensory neurons regulate the effector functions and
      phenotype of CD8+ T cells during active immunosurveillance of HSV-1 latency. Low
      level viral gene expression in latently infected sensory ganglia gives rise to a
      unique, functionally active CD8+ T cell population. Surprisingly, distinct
      neuronal subsets require different CD8 effector mechanisms to maintain viral
      latency, with some requiring IFN-gamma and others requiring lytic granules (LG).
      This nonredundant efficacy of CD8+ T cell effector mechanisms in maintaining
      viral latency is explained as follows: (1) a subset of neurons that expresses IFN
      gamma receptors (IFN-gamma R+) and Qa 1 responds to IFN-gamma, but Qa 1
      engagement of CD94/NKG2a blocks LG exocytosis by CD8+ T cells; (2) another
      neuronal subset is responsive to LG because it lacks Qa 1 and is refractory to
      IFN-gamma because it also lacks IFN-gamma R. In the latter subset, LG appear to
      provide a nonlethal block of viral reactivation.

PMID- 16286020
TI  - Lsc regulates marginal-zone B cell migration and adhesion and is required for the
      IgM T-dependent antibody response.
AB  - The humoral immune response to protein antigens is composed of a rapid low
      affinity IgM antibody response followed by an IgG response exhibiting higher
      affinity. Here, we demonstrate that Lsc, a protein that regulates G protein
      coupled-receptor signaling and RhoA activation, is required by B lymphocytes for
      the antigen-specific IgM antibody response to a protein antigen. We further show
      that in lsc(-/-) mice, MZB cells are selectively affected such that naive and in
      vivo-activated MZB cells migrate toward sphingosine-1-phosphate at increased
      proportions but release inefficiently from integrin ligands. Consequently, lsc(-/
      ) MZB cells do not traffick appropriately in an immune response and do not
      contribute to the TD antibody response. These data demonstrate that Lsc regulates
      the migration and adhesion of MZB cells, and this regulation appears to be
      required for these cells to contribute to the antibody response to TD antigens.

PMID- 16286021
TI  - Lymphotoxin-beta receptor signaling is required for the homeostatic control of
      HEV differentiation and function.
AB  - The lymphotoxin axis is important for the maintenance of several specialized
      lymphoid microenvironments in secondary lymphoid tissue. Lymphoid-tissue
      architecture is highly plastic and requires continual homeostatic signaling to
      maintain its basal functional state. The cellularity of lymph nodes in adult mice
      was reduced by systemic blockade of lymphotoxin-beta receptor (LTbeta R)
      signaling with a soluble decoy receptor both in resting and reactive settings.
      This reduction in cellularity resulted from greatly impaired lymphocyte entry
      into lymph nodes due to decreased levels of peripheral lymph node addressing
      (PNAd) and MAdCAM on high endothelial venules (HEV). LTbeta R signaling was
      required to maintain normal levels of RNA expression of MAdCAM, and also of PNAd
      by regulating the expression of key enzymes and scaffold proteins required for
      its assembly. Thus, the homeostatic maintenance of functional HEV status in adult
      mice relies largely on LTbeta R signaling.

PMID- 16286022
TI  - Fetal upper arm volume in predicting intrauterine growth restriction: a three
      dimensional ultrasound study.
AB  - As fetuses with intrauterine growth restriction (IUGR) may have increased risks
      with perinatal morbidity and mortality, prenatal diagnosis of IUGR is a very
      important issue in perinatology. To assess the efficacy of fetal upper arm volume
      in predicting IUGR, we undertook a prospective, cross-sectional study using
      quantitative three-dimensional (3D) ultrasound (US). In total, 40 fetuses with
      IUGR and 442 fetuses without IUGR were included for the upper arm volume
      assessment in utero by 3D US. All the fetuses were singletons and were followed
      up to delivery to establish whether they were complicated with IUGR or not. Our
      results showed that fetal upper arm volume assessed by 3D US can differentiate
      fetuses with IUGR from fetuses without IUGR well. The best predicting threshold
      for IUGR is at the 10th percentile by upper arm volume. Using the 10th percentile
      as the cutoff, the sensitivity of fetal upper arm volume in predicting IUGR was
      97.5%, with specificity 92.8%, predictive value of positive test 54.9%,
      predictive value of negative test 99.8% and accuracy 93.1%. Furthermore, upper
      arm volume is the best parameter for detecting IUGR among the common fetal
      biometric indices, such as biparietal diameter (BPD), occipitofrontal diameter
      (OFD), head circumference (HC), abdominal circumference (AC), femur length (FL)
      and estimated fetal weight (EFW). In conclusion, fetal upper arm volume assessed
      by quantitative 3D US can be used to predict fetuses with IUGR antenatally. We
      believe fetal upper arm volume assessment by 3D US would be a useful test in
      detecting fetuses with IUGR.

PMID- 16286023
TI  - Wall shear stress and related hemodynamic parameters in the fetal descending
      aorta derived from color Doppler velocity profiles.
AB  - This paper presents a methodology for estimating the wall shear stress in the
      fetal descending aorta from color Doppler velocity profiles obtained during the
      second half of pregnancy. The Womersley model was applied to determine the wall
      shear stress and related hemodynamic parameters. Our analysis indicates that the
      aortic diameter can be modeled as a function of the gestational age in weeks as:
      Diameter (mm) = 0.17.ga + 0.15 (R2 = 0.64, p < 0.001). The aortic volume flow
      showed a log linear gestational age-related increase that fit the model: F
      (mL/min) = e(0.08.ga + 3.49) (R2 = 0.61, p < 0.001). The Womersley number
      increased linearly with gestational age from 3.3 to 6.2 (p < 0.001) and the
      pressure gradient decreased linearly from 2.68 to 1.16 mPa/mm (p = 0.003) during
      the second half of pregnancy; the mean wall shear stress for the study group was
      2.2 Pa (SD = 0.59) and was independent of gestational age. This study suggests
      that the size of the fetal aorta adapts to flow demands and maintains constant
      mean wall shear stress.

PMID- 16286024
TI  - Development of a support vector machine-based image analysis system for assessing
      the thyroid nodule malignancy risk on ultrasound.
AB  - An SVM-based image analysis system was developed for assessing the malignancy
      risk of thyroid nodules. Ultrasound images of 120 cytology confirmed thyroid
      nodules (78 low-risk and 42 high-risk of malignancy) were manually segmented by a
      physician using a custom developed software in C++. From each nodule, 40 textural
      features were automatically calculated and were used with the SVM algorithm in
      the design of the image analysis system. Highest classification accuracy was
      96.7%, misdiagnosing two high-risk and two low-risk thyroid nodules. The proposed
      system may be of value to physicians as a second opinion tool for avoiding
      unnecessary invasive procedures.

PMID- 16286025
TI  - Elastography for the follow-up of high-intensity focused ultrasound prostate
      cancer treatment: initial comparison with MRI.
AB  - We previously developed an ultrasonic elastography imaging system that may
      provide a simple and cost-effective solution to monitor high-intensity focused
      ultrasound (HIFU) treatments. The objective of this clinical study was to
      evaluate the reliability of our system in assessing the volume of HIFU lesions in
      the prostate, using a comparison with magnetic resonance imaging (MRI).
      Elastograms were obtained in 20 patients after HIFU treatment for prostate cancer
      and gadolinium-enhanced T1- and T2-weighted MRI was performed. Lesion boundaries
      were manually outlined and the volume was calculated. A statistically significant
      correlation of rho = 0.62 (p = 0.022) was found between elastographic and MRI
      measurements of lesion volume, with elastographic measurements that generally
      underestimated the volume measured in MRI. Some basic physics (hypoechoic areas)
      and instrumentation (frame rate and band width) issues that were detrimental to
      image quality in vivo are reported, along with propositions to improve the
      technique. Because of these issues and, although good correspondence between
      elastographic and MRI measurements was found in some patients, elastographic
      measurements were unable to predict MRI measurements in a single individual.
      Nevertheless, the results confirmed the potential of elastography for monitoring
      HIFU treatment of the prostate. Further investigation will be conducted using
      better suited ultrasound equipment and performing real-time elastogram
      calculations.

PMID- 16286026
TI  - A needle tracking device for ultrasound guided percutaneous procedures.
AB  - A novel tracking device is proposed for measuring the position and orientation of
      a needle with respect to an ultrasound probe. This device is intended to guide an
      operator during a percutaneous needle insertion so that the needle trajectory can
      be visually aligned with the target before insertion. The tracking device uses a
      pair of cameras to track the needle location so that a standard needle can be
      used without attaching a separate sensor to the needle. The main challenge is to
      calibrate the tracking system with sufficient accuracy. Calibration methods are
      described for each of the system parameters. A series of tests show that an
      overall error of 3.1 +/- 1.8 mm is achieved with two commercial cameras and an
      error of 6.5 +/- 5.7 mm is achieved with two inexpensive consumer cameras. An
      analysis of the source of errors reveals that the errors arise from all of the
      calibration steps. Overall system accuracy is therefore determined by both the
      quality of the cameras and the performance of calibration.

PMID- 16286027
TI  - Ultrasound image segmentation using spectral clustering.
AB  - Segmentation of ultrasound images is necessary in a variety of clinical
      applications, but the development of automatic techniques is still an open
      problem. Spectral clustering techniques have recently become popular for data and
      image analysis. In particular, image segmentation has been proposed via the
      normalized cut (NCut) criterion. This article describes an initial investigation
      to determine the suitability of such segmentation techniques for ultrasound
      images. The adaptation of the NCut technique to ultrasound is described first.
      Segmentation is then performed on simulated ultrasound images. Tests are also
      performed on abdominal and fetal images with the segmentation results compared to
      manual segmentation. The success of the segmentation on these test cases warrants
      further research into NCut-based segmentation of ultrasound images.

PMID- 16286028
TI  - Speckle classification for sensorless freehand 3-D ultrasound.
AB  - Despite being a valuable tool for volume measurement and the analysis of complex
      geometry, the need for an external position sensor is holding up the clinical
      exploitation of freehand 3-D ultrasound. Some sensorless systems have been
      developed, using speckle decorrelation for out-of-plane distance estimation, but
      their accuracy is still not as good as that of sensor-based systems. Here, we
      examine the widely held belief that accuracy can be improved by limiting the
      distance measurements to patches of ultrasound data containing fully developed
      speckle. Without speckle detection, we observe that scan separation is
      systematically underestimated by 33.1% in biological tissue. We describe a number
      of speckle detectors and show that they reduce the underestimate to about 25%. We
      conclude that speckle classification can improve the quality of distance
      estimation, but not sufficiently to achieve accurate, metric reconstruction of
      the insonified volume.

PMID- 16286029
TI  - A general solution for catheter position effects for strain estimation in
      intravascular elastography.
AB  - Intravascular ultrasound (US) elastography reveals the elastic properties of
      vascular tissue and plaque. However, misalignment of the US catheter in the
      vessel lumen can cause incorrect strain estimation in intravascular US
      elastography caused by strain projection artifacts. In this paper, we present a
      general theoretical solution where the impact of catheter eccentricity, tilt and
      noncoplanar errors on the strain estimates are derived. Appropriate corrections
      to strain estimates can then be applied with prior knowledge of the catheter
      position information to reduce the strain projection artifacts. Simulations using
      a frequency-domain-based algorithm that models intravascular US imaging before
      and after a specified deformation are presented. The simulations are used to
      verify the theoretical derivations for two displacement situations (linear and
      nonlinear) under intraluminal pressure, with and without stress decay. The linear
      displacement case demonstrates that the correction factor is dependent only on
      the angle between the US beam and the cross-sectional plane of the vessel. For
      the nonlinear displacement case, where a l/r stress decay in the displacement is
      modeled, the correction factor becomes a more complicated function of the
      azimuthal angle.

PMID- 16286030
TI  - MRI-guided targeted blood-brain barrier disruption with focused ultrasound:
      histological findings in rabbits.
AB  - Focused ultrasound offers a method to disrupt the blood-brain barrier (BBB)
      noninvasively and reversibly at targeted locations. The purpose of this study was
      to test the safety of this method by searching for ischemia and apoptosis in
      areas with BBB disruption induced by pulsed ultrasound in the presence of
      preformed gas bubbles and by looking for delayed effects up to one month after
      sonication. Pulsed ultrasound exposures (sonications) were performed in the
      brains of 24 rabbits under monitoring by magnetic resonance imaging (MRI)
      (ultrasound: frequency = 1.63 MHz, burst length = 100 ms, PRF = 1 Hz, duration =
      20 s, pressure amplitude 0.7 to 1.0 MPa). Before sonication, an ultrasound
      contrast agent (Optison, GE Healthcare, Milwaukee, WI, USA) was injected IV. BBB
      disruption was confirmed with contrast-enhanced MR images. Whole brain histologic
      examination was performed using haematoxylin and eosin staining for general
      histology, vanadium acid fuchsin-toluidine blue staining for ischemic neurons and
      TUNEL staining for apoptosis. The main effects observed were tiny regions of
      extravasated red blood cells scattered around the sonicated locations, indicating
      affected capillaries. Despite these vasculature effects, only a few cells in some
      of the sonicated areas showed evidence for apoptosis or ischemia. No ischemic or
      apoptotic regions were detected that would indicate a compromised blood supply
      was induced by the sonications. No delayed effects were observed either by MRI or
      histology up to 4 wk after sonication. Ultrasound-induced BBB disruption is
      possible without inducing substantial vascular damage that would result in
      ischemic or apoptotic death to neurons. These findings indicate that this method
      is safe for targeted drug delivery, at least when compared with the currently
      available invasive methods.

PMID- 16286031
TI  - Miniaturized ultrasound arrays for interstitial ablation and imaging.
AB  - A potential alternative to extracorporeal, noninvasive HIFU therapy is minimally
      invasive intense ultrasound ablation that can be performed laparoscopically or
      percutaneously. An approach to minimally invasive ablation of soft tissue using
      miniaturized linear ultrasound arrays is presented here. Recently developed 32
      element arrays with aperture 2.3 x 49 mm, therapy frequency 3.1 MHz, pulse-echo
      bandwidths >42% and surface acoustic energy density >80 W/cm2, are described.
      These arrays are integrated into a probe assembly, including a coupling balloon
      and piercing tip, suitable for interstitial ablation. An integrated electronic
      control system allows therapy planning and automated treatment guided by real
      time interstitial B-scan imaging. Image quality, challenging because of limited
      probe dimensions and channel count, is aided by signal processing techniques that
      improve image definition and contrast, resulting in image quality comparable to
      typical transabdominal ultrasound imaging. Ablation results from ex vivo and in
      vivo experiments on mammalian liver tissue show that this approach is capable of
      ablation rates and volumes relevant to clinical applications of soft tissue
      ablation such as treatment of liver cancer.

PMID- 16286032
TI  - The effect of sonication on simulated osteoarthritis. Part I: effects of 1 MHz
      ultrasound on uptake of hyaluronan into the rabbit synovium.
AB  - High molecular weight (MW) hyaluronan (HA) preparation is considered to be more
      biologically active than HAs of lower MWs. However, many of the HA preparations
      currently used to treat osteoarthritis (OA) have lower MWs by the enhanced
      penetration of HA molecules into the synovial lining cells. In this study, we
      determined the effectiveness of sonophoresis on the delivery of high MW HA into
      synovial membrane using an animal model of OA. A total of 1000 kDa (HA1000) and
      3000 kDa (HA3000) HA were labeled with fluorescein and injected into the knees of
      rabbits. Low-intensity continuous ultrasound at 1 MHz, 400 mW/cm2 was applied to
      the knees for 10 min treatment bid. Synovial fluid analysis revealed increased
      absorption and fluorescence microscopy showed deeper penetration of both HA1000
      and HA3000, more so with the latter. Histologic examination indicated that
      ultrasound treatment resulted in no apparent damage to the synovial membrane.
      These results suggest that simultaneous sonication with HA injection might
      compensate for the short half-life of HA. Consequently, this dual treatment would
      render HA a far more effective tool in the management of OA.

PMID- 16286033
TI  - The effect of sonication on simulated osteoarthritis. Part II: alleviation of
      osteoarthritis pathogenesis by 1 MHz ultrasound with simultaneous hyaluronate
      injection.
AB  - In our previous study, we demonstrated the effects of ultrasound (US) on the
      delivery of hyaluronan (HA) into the synovium, even at molecular sizes as high as
      3000 kDA. We hypothesized that a combined therapy with US and HA would have
      synergistic effects on alleviating the pathogenesis of osteoarthritis (OA). In
      the present study, we evaluated the effectiveness of sonication on the progress
      of induced OA in rabbits. We measured the cartilage degradation and inflammation,
      synovial fluid amount along with protein content and, finally, performed
      histologic analyses of the integrity of the cartilage and synovium. Low-intensity
      continuous US at 1 MHz, 400 mW/cm2 was applied to the knees for 10 min bid.
      Combined treatment with US and HA most strikingly reduced total synovial fluid
      volume and also significantly alleviated the OA-induced accretion of total
      protein, proteoglycan and prostaglandin E2 in the synovial fluid. It also
      attenuated the release of collagen type II and matrix metalloproteinase-3 in the
      OA-induced joint to normal levels. Histopathology revealed that combined HA and
      US treatment also reduced the severity of OA-induced structural damages in the
      cartilage and synovium. The effectiveness of HA with regard to the alleviation of
      OA pathogenic changes can be greatly enhanced by the simultaneous treatment with
      HA and US.

PMID- 16286034
TI  - Detection of blood coagulation and clot formation using quantitative ultrasonic
      parameters.
AB  - The ultrasonic parameters of sound velocity, attenuation and integrated
      backscatter were applied to detect the process of coagulation and clot formation
      in porcine blood. Fresh porcine blood containing 15% anticoagulant solution was
      collected. Blood samples with a hematocrit of 45% were obtained by reconstituting
      the packed erythrocytes with the separated plasma for ultrasound measurements
      performed with a 10-MHz focused transducer. A 24-mL aliquot of blood was placed
      in a container and 12 mL of 0.2 mol/L CaCl2 solution was added to induce clot
      formation. In each measurement, radio-frequency signals of the blood digitized at
      100 MHz were collected for 50 min at a temporal resolution of 1 A-line per s.
      Results showed that all of the parameters increased within the initial 3 min and,
      then, immediately decreased dramatically as the CaCl2 solution was added.
      Subsequently, the sound velocity gradually increased with time and the integrated
      backscatter and attenuation increased in accordance with blood coagulation until
      approximately 500 and 2600 s, respectively. The integrated backscatter,
      attenuation and sound velocity can be divided into different stages, including
      red cell aggregation, reduction in hematocrit, blood coagulation and clot
      formation, corresponding to variations in the physical and chemical properties of
      the blood. The integrated backscatter, attenuation and sound velocity increased
      because of the changes in blood properties during the process of coagulation and
      clot formation: by 8.2 dB, 0.65 dB/cm, and 0.6%, respectively. These results
      provide a feasibility for further applying ultrasonic parameters to in vivo
      monitor the progress of clotting and thrombosis research.

PMID- 16286035
TI  - A culture of accountability.

PMID- 16286036
TI  - Determinants of plaque instability in atherosclerotic vascular disease.
AB  - BACKGROUND: Despite numerous advances in the understanding of the pathogenesis of
      atherosclerosis, the factors that determine atheromatous plaque instability
      remain unclear. The prediction of the vulnerability of a plaque to rupture and
      subsequent thrombosis would be useful in guiding development of diagnostic and
      therapeutic approaches. METHODS: Aortas with areas of gross atherosclerosis were
      obtained from seven autopsy cases. These were then serially sectioned at 3-mm
      intervals, analyzed histologically, and scored as to plaque size, calcification,
      lipid content, intraplaque hemorrhage, inflammation, plaque disruption, and
      plaque thrombosis. Bivariate correlations and binary multivariate regression
      analyses were performed using SPSS software. RESULTS: Plaque instability was
      highly correlated with intraplaque hemorrhage, lipid content, and plaque size.
      Weaker but statistically significant correlations were found with inflammation
      and calcification. However, in multivariate regression analyses, only plaque
      size, intraplaque hemorrhage, and lipid content, independent predictors of plaque
      instability, were significant. CONCLUSIONS: Atheromatous plaques may be rendered
      unstable by increases in size, increased intra- and extracellular lipid
      accumulation, and intraplaque hemorrhage. Based on these results, diagnostic
      modalities that detect plaque size, plaque hemorrhage, and/or lipid content are
      most likely to be useful in predicting unstable plaques.

PMID- 16286037
TI  - A study of neovascularization in the rat ischemic hindlimb using Araldite casting
      and Spalteholtz tissue clearing.
AB  - INTRODUCTION: Understanding neovascularization is an important prerequisite for
      therapeutic advances aimed at the salvation of ischemic tissues. We explored an
      alternative strategy to corrosion casting for visualizing neovascularization in a
      rat hindlimb ischemia model. METHODS: Rats were subjected to hindlimb ischemia by
      femoral artery ligation. Directly after femoral artery occlusion and at 7, 14, 21
      and 28 days postsurgery, rats were sacrificed, and neovascularization was
      evaluated by vascular casting with Araldite plastic and subsequent Spalteholtz
      tissue clearing. RESULTS: Semitransparent preparations were obtained, in which
      the casted arteries could be directly and three-dimensionally visualized in
      detail and in relation to the surrounding tissue. In the vascular casts,
      collateral formation and recanalization of previously thrombosed arteries were
      demonstrated. CONCLUSIONS: We describe an alternative approach to study
      neovascularization in animal models. This method, which combines Araldite plastic
      vascular casting with Spalteholtz tissue clearing, preserves all vasculature as
      well as the surrounding tissue. In a small time series in rat ischemic hindlimbs,
      we show that restoration of blood flow after ischemia not only involves newly
      formed collaterals, but also recanalization of previously thrombosed arterial
      segments.

PMID- 16286038
TI  - Giant aneurysms of coronary arteries and saphenous vein grafts: angiographic
      findings and histopathological correlates.
AB  - INTRODUCTION: Giant aneurysms that develop in native coronary arteries or
      saphenous vein grafts are morphologically defined as abnormally expanded
      outpouching vascular structures >4 cm in diameter. The location, morphology, and
      content of giant aneurysms account for adverse cardiovascular effects. METHODS:
      Two cases of giant aneurysms were studied comprehensively by noninvasive and
      invasive cardiac methods and subsequent histopathology. The first patient had a
      giant aneurysm that developed over a course of several years in a saphenous vein
      graft whereas the second patient had a giant aneurysm occurring within a native
      coronary artery. Accompanying clinical and angiographic findings are described.
      RESULTS: Atherosclerosis and thrombosis were among the prominent
      histopathological findings. CONCLUSIONS: Atherosclerosis and associated
      thrombosis within giant aneurysms result in obstruction of flow, distal
      embolization, and development of acute coronary syndromes including recurrent
      ischemic chest pain, unstable angina, and acute myocardial infarction. The
      options for clinical management of giant coronary or vein graft aneurysms include
      surgical excision, percutaneous coil occlusion and stent deployment, or medical
      approach.

PMID- 16286039
TI  - Solitary coronary ostium in the aorta in Syrian hamsters. A morphological study
      of 130 cases.
AB  - BACKGROUND: Solitary coronary ostium in the aorta (SCOA) is a rare anomaly, the
      pathogenesis of which remains uncertain. The lack of an animal model is one of
      the reasons why little understanding of this question has been gained. The aim
      was to examine the coronary distribution patterns associated with SCOA in
      laboratory inbred Syrian hamsters. METHODS: The study concerns 130 cases detected
      in a database consisting of 1,202 internal casts of the heart, great arterial
      trunks, and coronary arteries. RESULTS: In 21 (16.2%) cases, the solitary ostium
      was located in the left aortic sinus. In a further 58 (44.6%) cases, it was in
      the right aortic sinus. In the remaining 51 (39.2%) cases, the ostium was in the
      right side of the ventral aortic sinus of a bicuspid aortic valve. The
      distribution patterns were classified according to the location of the solitary
      ostium and the presence, or absence, and course of the main coronary arterial
      vessels. Overall, 14 categories were established, 10 of which had their
      counterpart in man. CONCLUSIONS: The findings reported substantiate the use of
      the present inbred Syrian hamsters for further studying the morphogenesis of the
      SCOA. The results of a statistical analysis indicate that when a sole coronary
      ostium becomes established in the aortic root, the development of the resultant
      anomalous coronary arterial tree tends to happen through preferential pathways.
      In addition, they indicate that the branching mode of the coronary tree and the
      condition of the aortic valve are independent traits.

PMID- 16286040
TI  - Toward a cardiovascular pathology training report on the forum held in Vancouver,
      March 6, 2004, Society for Cardiovascular Pathology.
AB  - Cardiovascular pathology is a subspecialty of anatomic pathology that requires
      both clinical education and expertise in contemporary physiopathology. The
      Society for Cardiovascular Pathology sponsored a special workshop within the
      frame of the USCAP Annual Meeting, held in Vancouver, March 6-12, 2004, to
      address the present and future role of cardiovascular pathology in research,
      clinical care, and education. Clearly, the recruitment and training of young
      pathologists are crucial to this aim. The forum tried to answer a series of
      questions. First, is there room for cardiovascular pathologists and
      clinicopathologic correlations in the era of extraordinary advances of in vivo
      human body imaging? What is the evolving role of the autopsy? How can the
      cardiovascular pathologist simultaneously be an autopsy prosector, a surgical
      pathologist, a molecular pathologist, and an experimental pathologist? Is there a
      specific domain content for training in cardiovascular pathology and does it meet
      the constellation of market needs and demands? What are the experiences in
      Europe, North America and elsewhere? What is the influence of cardiovascular
      pathology in departments of pathology? Is the subdiscipline still a Cinderella in
      the anatomic theatre or a Princess with a double helix coat of arms? The Society
      for Cardiovascular Pathology is strongly committed to optimizing the academic and
      professional profile of the future generation of cardiovascular pathologists.
      This article reports the outcome of the forum and directions that may lead to a
      vibrant future for well-trained cardiovascular pathologists.

PMID- 16286041
TI  - Takayasu aortitis with acute dissection and hemopericardium.
AB  - We report a case of a 57-year-old woman with an unremarkable past medical history
      who presented to the emergency department with maxillary pain that later radiated
      to the chest. She died less than 12 h after admission. CT findings were
      consistent with ascending aorta dissection with hemopericardium. Autopsy revealed
      a tear immediately proximal to the ostium of the brachiocephalic artery and a
      dissecting flap with false lumen, rupture, and hemopericardium. Histologically,
      there was a zonal medial necrosis with surrounding chronic inflammation, focal
      destruction of the media, and fibrosis of the intima and adventitia. A diagnosis
      of granulomatous necrotizing aortitis of Takayasu type was made. This case
      demonstrates a rare example of aortitis underlying aortic dissection and
      emphasizes the need for careful histologic examination in cases of aortic root
      disease.

PMID- 16286042
TI  - Chronic lymphocytic leukemia involving the coronary arteries with accompanying
      acute myocardial infarction.
AB  - An 83-year-old man with chronic lymphocytic leukemia (CLL) for 10 years presented
      with dyspnea and hypotension. Blood investigations and electrocardiogram were
      consistent with acute myocardial infarction. The patient deteriorated quickly and
      died shortly thereafter. At autopsy, there was severe atherosclerosis of the
      coronary arteries and an inferolateral left ventricular wall myocardial infarct.
      Microscopy showed that CLL involved the nodes, liver, spleen, bowel, and kidneys.
      The coronary artery walls were infiltrated with leukemia cells invading the
      tunica media and the atheromatous plaque. Infiltration of the coronary arteries
      by CLL is not common and the possible role in coronary syndromes is discussed.

PMID- 16286043
TI  - Incidental finding of right renal venous aneurysm in a patient with symptomatic
      ipsilateral renal carcinoma: a case report.
AB  - BACKGROUND: True venous aneurysms of the renal veins are very uncommon lesions.
      Diagnosis is incidental, and thrombosed aneurysms may simulate solid renal
      masses. METHODS AND RESULTS: A case of right renal vein aneurysm incidentally
      found in a patient with a ispilateral renal carcinoma and abdominal aortic
      aneurysm is reported. While CT examination suggested a high-flow arteriovenous (A
      V) malformation, a selective angiographic study identified two separate and
      independent pathologic conditions (venous aneurysm and intratumoral, acquired A-V
      fistulae). Successful preoperative embolization of the renal tumor was obtained
      and surgical treatment (nephrectomy+aneurysmectomy) was uneventful. CONCLUSIONS:
      Although uncommon, venous renal aneurysms require an accurate preoperative
      diagnosis; this case is interesting because the coexistence of renal tumor with
      acquired A-V fistulae raised the prospect of a large, high-flow A-V communication
      with secondary venous enlargement. The integrated imaging studies were basic to
      differentiate acquired, tumor-induced A-V fistulae found in the lower renal pole
      from the true venous aneurysm located in the upper pole. To our knowledge, this
      is the first report of such a condition.

PMID- 16286044
TI  - Primary synovial sarcoma of the mitral valve.
AB  - Primary cardiac synovial sarcoma is a rare malignancy, comprising approximately
      5% of cardiac sarcomas and less than 0.1% of all primary cardiac tumors. Herein,
      we describe a synovial sarcoma arising on the anterior mitral leaflet in a 66
      year-old man. The histopathologic diagnosis was supported by the
      immunohistochemical profile and the presence of the SYT-SSX1 fusion transcript
      identified by molecular genetic studies.

PMID- 16286045
TI  - Infarcted appendix epicardica.

PMID- 16286046
TI  - Small vessel vasculitis.
AB  - BACKGROUND: Vasculitis is a primary inflammatory process of large, medium-sized,
      and small blood vessels. There are multiple entities particularly among small
      vessel vasculitides. Some are life threatening and require treatment with toxic
      agents. Diagnostic challenges are posed by low prevalence, controversial
      classification, inconsistency of clinical and pathological features, and the
      existence of clinical and pathological "look-alikes". Also, patients may present
      to a variety of medical specialists, and the diagnosis is often unexpected. The
      cause often is unknown. REVIEW: Classification is by vessel size and then on an
      immunopathologic basis. Generalised and "organ-limited" forms occur. The
      principal clinical and pathological features are outlined for each of
      antibasement membrane disease, immune complex disorders including Henoch
      Schonlein purpura and cryoglobulinemic vasculitis and the pauci-immune group,
      which is often associated with antineutrophil cytoplasmic antibody (ANCA),
      comprising microscopic polyangiitis, Wegener's granulomatosis, and Churg-Strauss
      syndrome. A brief account is given of "look-alikes" including microthrombotic
      conditions, which can confound the diagnosis of small vessel vasculitis.
      CONCLUSION: Requirements for diagnosis include full disclosure of the past and
      present medical history with review of laboratory results, especially diagnostic
      immunology. Histology should be of targeted biopsies of recent active lesions in
      preference to blind biopsies. Sampling should be extensive using high-quality
      thin sections. Systematic microscopic evaluation of architectural features and
      cellular detail is necessary. Tissue immunofluorescence is a useful adjunct. The
      final opinion must take all available information into account but may ultimately
      depend on a critical judgement by the pathologist.

PMID- 16286047
TI  - Comprehensive comparison of the VERSANT HIV-1 RNA 3.0 (bDNA) and COBAS AMPLICOR
      HIV-1 MONITOR 1.5 assays on 1,000 clinical specimens.
AB  - BACKGROUND: Plasma human immunodeficiency virus type 1 (HIV-1) RNA level is an
      important parameter for patient management, yet viral load assays from different
      manufacturers are not standardized. OBJECTIVES AND STUDY DESIGN: In this study,
      we evaluated the concordance between test results obtained for 1,000 plasma
      specimens collected from HIV-1-infected individuals measured with the VERSANT HIV
      1 RNA 3.0 assay (bDNA) and the COBAS AMPLICOR HIV-1 MONITOR 1.5 test (PCR). We
      compared viral load values obtained by each of these assays throughout their
      dynamic ranges, with particular focus on samples with low viral load (i.e. 50-250
      copies/mL), and calculated the estimated distribution of distinct plasma viral
      load levels for the entire study population modeled from the data observed in the
      study. RESULTS: We found that these two assays show excellent agreement, with a
      correlation (R(2)) of 0.957 and a slope of 1.004. The mean difference in viral
      load values between the two assays was less than 0.10-log(10) throughout the
      dynamic range and 98.2% of all samples had bDNA and PCR results within 0.5
      log(10) of each other, a difference that is within the range considered to be a
      minimal change in plasma viremia. Moreover, the two assays show very similar
      results across all assay ranges tested. The estimated prevalence of samples with
      results <50 copies/mL, 50-250 copies/mL, and 250-500,000 copies/mL were 41.6%,
      7.7%, and 49.7%, respectively, by the bDNA assay, and 42.4%, 6.9%, and 50.7%,
      respectively, by the PCR assay. CONCLUSION: Based on our findings from 1,000
      clinical specimens, we do not see the need to re-establish a baseline value or
      apply a conversion factor when switching from one assay to the other. Since the
      majority of our patient population likely is infected with subtype B virus, it is
      unclear if our findings will apply to other patient populations with a greater
      incidence of infection with non-B subtypes.

PMID- 16286048
TI  - TaqMan RT-PCR and VERSANT HIV-1 RNA 3.0 (bDNA) assay Quantification of HIV-1 RNA
      viral load in breast milk.
AB  - BACKGROUND: Transmission of HIV via breast milk is a primary cause of pediatric
      HIV infection in developing countries. Reliable methods to detect breast milk
      viral load are important. OBJECTIVE: To correlate the ability of the VERSANT HIV
      3.0 (bDNA) assay to real-time (RT) TaqMan PCR in quantifying breast milk HIV-1
      RNA. STUDY DESIGN: Forty-six breast milk samples that had been spiked with cell
      free HIV-1 and eight samples spiked with cell-associated HIV-1 were assayed for
      HIV-1 RNA by both VERSANT HIV 3.0 and TaqMan RNA assays. RESULTS: Only assays on
      the cell-free samples were statistically compared. Both a Deming regression slope
      and a Bland-Altman slope indicated a linear relationship between the two assays.
      TaqMan quantitations were on average 2.6 times higher than those of HIV 3.0. A
      linear relationship was observed between serial dilutions of spiked cell-free HIV
      1 and both the VERSANT HIV 3.0 and the TaqMan RNA assays. CONCLUSION: The two
      methods correlated well although the VERSANT HIV 3.0 research protocol quantified
      HIV-1 RNA slightly lower than TaqMan.

PMID- 16286049
TI  - Detection and quantification of proviral HIV-1 184 M/V in circulating CD4(+) T
      cells of patients on HAART with a viremia less than 1,000 copies/ml.
AB  - BACKGROUND: Highly active anti-retroviral therapy (HAART) effectively reduces HIV
      replication but does not completely hinder it. Sub-optimal therapy leads to HIV
      resistance to the drugs administered. However, the role of low-level viremia
      (viral-load less than 1,000 copies/ml) on mutation genesis and incorporation of
      resistant forms in the long-lived CD4(+) T cellular DNA compartment is not clear.
      OBJECTIVE: To investigate the relationship between lamivudine associated mutant
      type 184 V and the wild-type 184 M proviral forms in the circulating CD4(+) T
      cells of patients and low-level viremia. STUDY DESIGN: Cross-sectional study of
      50 patients on long-term HAART, with a viremia of less than 1 000 copies/ml.
      Patients were stratified into three groups; on lamivudine, group I (viral load
      <20 copies/ml), group II (viral load 20-1000 copies/ml) and as lamivudine
      experienced, group III (viral load <1000 copies/ml). 184 M and 184 V proviral HIV
      1 was detected and quantified by a specific and sensitive assay combining a
      TaqMan real-time PCR analysis with the amplification-refractory mutation system
      (ARMS) principle. RESULTS: Fifty-six percent of patients with low-level viremia
      had 184 V in the CD4(+) T cellular DNA compartment as compared to only 8% in
      those with undetectable viremia. The presence of 184 V was significantly
      associated with a higher viral load (P=0.001). Patients with low-level viremia
      without 184 V in the CD4(+) T cellular DNA compartment, had a median plasma viral
      load of 135 copies/ml, while patients harbouring 184 V had a median viral load of
      498 copies/ml (P=0.006). No significant differences between the groups were
      observed in proviral HIV-1 DNA load. CONCLUSIONS: The frequency of the 184 V
      mutation was significantly lower, in the CD4(+) T cellular compartment of
      patients with a viral load of less than 20 copies/ml as compared to patients with
      a viremia of 20-1,000 copies/ml. Viremia, sustained below 20 copies/ml may
      prevent the appearance of 184 V mutation in this reservoir and therefore should
      be the objective of treatment.

PMID- 16286050
TI  - Comparative performance evaluation of the HIV-1 LiPA protease and reverse
      transcriptase resistance assay on clinical isolates.
AB  - BACKGROUND: Assays that provide information regarding HIV-1 resistance to
      antiretroviral drugs are widely used to help manage antiretroviral treatment. The
      most commonly used HIV genotypic resistance assays are based on DNA sequencing
      (TRUGENE, ViroSeq, and home-brew) or reverse hybridization (LiPA). OBJECTIVES:
      This study compares the results from clinical specimens using two assay methods:
      the LiPA HIV-1 protease (PR) and reverse transcriptase (RT) resistance assay and
      DNA sequencing. STUDY DESIGN: Operators at each of three sites tested 10-20
      randomly selected clinical specimens using LiPA (three strips total with probes
      for PR codons 30, 46, 48, 50, 54, 82, 84, and 90, and RT codons 41, 69, 70, 74,
      75, 103, 106, 151, 181, 184, and 215) and DNA sequencing (TRUGENE) HIV-1
      Genotyping Assay or home-brew methodology). Results from the two methods were
      categorized for each codon as follows: (i) concordant (LiPA and sequencing having
      the same result for wild-type (WT), mutant, and mixture); (ii) partially
      concordant (mixture by one method and not by the other); (iii) indeterminate (no
      result by LiPA); and (iv) discordant (LiPA and sequencing detecting different
      amino acids). RESULTS: A total of 50 clinical specimens were tested using the
      LiPA PR strip; 40 of these were also tested using the LiPA RT strip. For PR,
      91.3% of the codon results were concordant, 3.0% were partially concordant, 4.5%
      were indeterminate by LiPA, and 1.3% were discordant. For RT, 88.0% of the codon
      results were concordant, 5.9% were partially concordant, 5.2% were indeterminate,
      and 0.9% were discordant. LiPA detected 3.0% (PR) and 6.4% (RT) WT/mutant
      mixtures, compared to 0.5% (PR) and 3.2% (RT) mixtures by sequencing.
      CONCLUSIONS: More WT/mutant mixtures were detected using LiPA, possibly
      indicating increased sensitivity. Relatively high concordance and low discordance
      rates were observed between LiPA and DNA sequencing. The indeterminate rate for
      LiPA was moderately high and may limit the clinical utility of this assay.

PMID- 16286051
TI  - HIV-1 drug resistance in Thailand: before and after National Access to
      Antiretroviral Program.
AB  - BACKGROUND: The Ministry of Public Health (Thailand), MoPH, has had a program
      called National Access to Antiretroviral Program for People who have AIDS (PHA)
      or "NAPHA", to offer free antiretroviral drugs (ARV), which are locally produced
      in Thailand, to any HIV-1 infected patients with CD4<200 since 2002. This program
      may increase usage of ARV therapy and the emergence of HIV-1 drug resistance.
      OBJECTIVES: To monitor HIV-1 ARV drug resistant codon mutation in Thailand before
      and after the "NAPHA" program. MATERIALS AND METHODS: EDTA blood samples were
      collected from 542 HIV-1 infected subjects, who received ARV therapy in 1999 and
      2001-2003, and perinatal chemoprophylaxis in 1998 and 2000. HIV-1 pol nucleotide
      sequences were analyzed. RESULTS: The percentage of drug resistant detection from
      the ARV therapy group in 1999 and 2001-2003 were 12.14 (34/280), 10.23 (9/88),
      86.96 (20/23) and 57.55 (61/106), respectively. Of 332 NRTI drug resistant codon
      mutation, 226 (68.07%) were thymidine analogue mutations (TAMs). The percentage
      of TAMs detection in 1999 and 2001-2003 were 7.14 (20/280), 9.09 (8/88), 56.52
      (13/23) and 43.34 (46/106), respectively. Of 105 NNRTI drug resistant codon
      mutation, 95 (90.48%) were related to nevirapine drug resistance. CONCLUSION:
      Thailand may need more appropriate monitoring of drug resistance in the free ARV
      therapy program to protect the future usage of drugs by minimizing the emergence
      of drug resistance.

PMID- 16286052
TI  - Clonal analysis of HIV-1 variants in proviral DNA during treatment interruption
      in patients with multiple therapy failures.
AB  - BACKGROUND: Treatment interruption (TI) in antiretroviral-treated patients on
      virological failure (VF) often results in a shift from resistant to wild-type HIV
      1 in plasma. A clonal analysis was set out to determine the importance of
      archiving of resistant HIV-1 variants during TI and its relationship with the
      occurrence of a VF after treatment resumption. METHODS: A fragment of the pol
      gene was cloned and sequenced from peripheral blood mononuclear cells DNA sampled
      at the end of TI. Clonal sequences were compared to bulk plasma sequences
      determined before TI, after TI and at VF. RESULTS: Four patients were enrolled;
      all had a complete reversion to wild-type HIV-1 at the end of TI. In two patients
      with subsequent VF, archiving of minority resistant variants was detected in
      proviral DNA. Archived resistant variants were found to be phylogenetically
      linked to sequences detected before TI and at VF, suggesting the re-expansion of
      resistant HIV-1 from archived quasi-species. CONCLUSION: In patients having a TI
      in the context of VF, archiving of resistant HIV-1 variants in proviral DNA can
      be involved into the mechanisms of further VF after treatment resumption.

PMID- 16286053
TI  - Dynamics of enfuvirtide resistance in HIV-infected patients during and after long
      term enfuvirtide salvage therapy.
AB  - Enfuvirtide (ENF) is the first of a novel class of drugs that blocks HIV fusion
      to host cells. We analyzed the dynamics of genotypic and phenotypic resistance to
      ENF during and after long-term ENF therapy and its clinical implications in eight
      heavily treatment-experienced HIV-infected patients who underwent salvage therapy
      with enfuvirtide along with other antiretroviral agents. All patients showed a
      rapid decline in plasma HIV-RNA followed by viral rebound. Changes at codons 36,
      42, 43 and/or 44 within the HR1 region of gp41 were selected in all cases,
      resulting in high-level phenotypic resistance to ENF, ranging from 15- to 445
      fold. Both genotypic and phenotypic resistance to ENF rapidly disappeared after
      discontinuation of the drug, suggesting that ENF-resistant viruses may have an
      impaired replicative capacity.

PMID- 16286054
TI  - CCR2-64I and CXCL12 3'A alleles confer a favorable prognosis to AIDS patients
      undergoing HAART therapy.
AB  - BACKGROUND: The chemokine receptor polymorphisms CCR5Delta32, CXCL12 3'A, CCR2
      64I and CCR5-59029 G/A have been demonstrated to affect HIV-1 infection and
      progression. OBJECTIVE: We studied the impact of the above polymorphisms on the
      effectiveness of a 30-month treatment with highly active antiretroviral therapy
      (HAART) in 149 HIV-1 patients. STUDY DESIGN: We stratified the patients according
      to CD4 CDC criteria and applied Kaplan-Meier analysis using the following end
      point criteria: (a) the time from HAART initiation to undetectable viral load
      (VL) counts (VL<50 copies/ml), (b) the duration of undetectable VL status and (c)
      the time required for CD4+ T-cell counts to pass over the 500 cells/ml threshold.
      RESULTS: Our results in the second group (CD4 201-500) revealed that patients
      with the CCR2-64I allele achieved undetectable VL counts at 3.5+/-0.48 months as
      compared to 10.26+/-1.42 months in the control group (p=0.018). The VL remained
      undetectable for 28+/-2 months, in contrast to 20+/-2 months in the control group
      (p=0.048). Patients carrying CXCL12 3'A restored the CD4 population faster than
      the control group (9+/-2 and 14+/-2 months, respectively, p=0.023). The
      CCR5Delta32 and CCR5-59029 G/A alleles did not appear to affect the parameters
      studied. CONCLUSIONS: Our results suggest that patients carrying either CCR2-64I
      or CXCL12 3'A have a more favorable prognosis during HAART treatment.

PMID- 16286055
TI  - Distribution of HIV/AIDS protective SDF1, CCR5 and CCR2 gene variants within
      Cretan population.
AB  - An interesting finding in the epidemiology of human immunodeficiency virus (HIV)
      infection is that certain mutations in genes coding for chemokine receptors and
      their ligands may confer resistance to HIV-1 infection and/or AIDS progression.
      The mutations most frequently studied are the CCR5-delta32, CCR2-64I and SDF1
      3'A. We examined the frequency of the above polymorphisms within the Cretan
      population, evaluating their contribution to a protective genetic background
      against HIV infection and progression. Two hundred blood samples were recruited
      at random among prospective blood donors from Crete. Genotyping was initially
      performed by polymerase chain reaction (PCR) analysis. CCR2 and SDF-1 PCR
      amplified genomic regions were further subjected to restriction fragment length
      polymorphism (RFLP) analysis for genotype determination. The CCR5-delta32 allele
      frequency among our study group was 3.25%, although no respective homozygous
      samples were detected. The screening for the CCR2-64I polymorphism yielded 39
      heterozygous (19.5%) and 4 homozygous (2%) subjects, revealing a CCR2-64I allele
      frequency of 11.75%. Among our 200 PCR-RFLP analysed samples, 73 (36.5%) were
      found heterozygous and 23 (11.5%) homozygous for the SDF1-3'A mutant variant. The
      allele frequency of the above polymorphism reached 29.75%. The frequency of the
      CCR5-delta32 allele among our study population seems to be remarkably lower
      compared to previously reported frequencies in other Caucasian groups. However,
      the SDF1-3'A allele frequency shows significantly higher distribution profiles
      within our study group compared to those observed in other Caucasian-European
      populations. The indicated difference could be attributed to the increased
      homogeneity of our population, which is well balanced and dispersed over a small
      geographical area. Since this polymorphism is related with delayed progression
      from HIV infection to AIDS, it could be used for prognostic genotyping in HIV
      infected Cretan individuals.

PMID- 16286056
TI  - Inhaled zanamivir versus rimantadine for the control of influenza in a highly
      vaccinated long-term care population.
AB  - BACKGROUND: Despite vaccination, influenza commonly causes morbidity and
      mortality in institutional settings. Influenza control with rimantadine and
      amantadine is limited by emergence and transmission of drug-resistant influenza A
      variants, ineffectiveness against influenza B, and toxicity. This study evaluated
      the efficacy and tolerability of zanamivir versus rimantadine for influenza
      outbreak control in long-term care facilities. METHODS: This double-blind,
      randomized, controlled study prospectively enrolled nursing home residents for 3
      influenza seasons (1997 to 2000). Vaccine was offered to all subjects. Following
      influenza outbreak declaration, subjects were randomized to inhaled zanamivir 10
      mg or standard of care (rimantadine 100 mg for influenza A or placebo for
      influenza B) once daily for 14 days. The proportion of randomized subjects
      developing symptomatic, laboratory-confirmed influenza during prophylaxis was the
      primary endpoint. RESULTS: Of 482 randomizations (238 zanamivir, 231 rimantadine,
      13 placebo), 96% of subjects were elderly or had high-risk conditions; over 90%
      were vaccinated. Symptomatic, laboratory-confirmed influenza occurred in 3% of
      zanamivir subjects and 8% of rimantadine subjects during chemoprophylaxis (P =
      .038; additional protective efficacy for zanamivir over rimantadine = 61%). Since
      only 25 subjects were randomized during 2 influenza B outbreaks and none
      developed influenza, the influenza B data were excluded from further analysis.
      Zanamivir was well tolerated and unassociated with emergence of resistant virus;
      rimantadine-resistant variants were common. CONCLUSIONS: This is the first
      prospective, controlled study demonstrating effectiveness of chemoprophylaxis for
      influenza outbreak control. Zanamivir prevents symptomatic, laboratory-confirmed
      influenza more effectively than rimantadine, is unassociated with resistant
      virus, and has a favorable safety profile. Zanamivir is an appropriate
      alternative for influenza outbreak control among institutionalized vaccinated
      elderly.

PMID- 16286057
TI  - Inhaled zanamivir versus placebo for the prevention of influenza outbreaks in an
      unvaccinated long-term care population.
AB  - BACKGROUND: Antiviral chemoprophylaxis effectiveness for influenza control has
      not been prospectively established for unvaccinated residents of long-term care
      facilities. This study evaluated the efficacy and tolerability of zanamivir
      against the standard of care (no intervention, ie, placebo) for influenza
      outbreak control in a largely unvaccinated institutionalized population.
      OBJECTIVE: To evaluate the efficacy and tolerability of zanamivir versus placebo
      for influenza outbreak control in long-term care facilities. METHODS: This double
      blind, randomized, placebo-controlled study prospectively enrolled/followed
      residents of long-term care facilities (LTCF) at 12 centers for 1 to 3 influenza
      seasons (1997 to 2000). Following influenza outbreak declaration, asymptomatic
      subjects were randomized for prophylaxis to inhaled zanamivir 10 mg or inhaled
      placebo given once daily for 14 days. The proportion of randomized subjects who
      during prophylaxis developed symptomatic, laboratory-confirmed influenza (SLCI)
      was the primary end point. RESULTS: Influenza outbreaks were explosive. The
      attack rates varied from 9.5 to 14.8 per 100 residents. Of 1763 consents given
      and resulting in 494 randomizations, 49% received zanamivir and 51% placebo; 66%
      were elderly and 9% were vaccinated. SLCI occurred in 6% of zanamivir and 9% of
      placebo subjects (P = .355; protective efficacy for zanamivir = 29%, 95%
      confidence interval 31% to 62%), and symptomatic influenza confirmed by culture
      in 2% and 6%, respectively (P = .052; protective efficacy = 65%, 95% confidence
      interval 8.5% to 86%). Zanamivir use was also associated with a 70% (95%
      confidence interval 13% to 89%) reduction in laboratory-confirmed influenza with
      fever (2% vs 6%, P = .043). Influenza B was not detected. Zanamivir was well
      tolerated. No virus isolate demonstrated zanamivir resistance. CONCLUSIONS: The
      protective efficacy of zanamivir versus placebo for SLCI was marginal, for all
      laboratory confirmed illnesses, but significant against culture proven and
      febrile influenza, suggesting zanamivir can be effective for outbreak control and
      symptom reduction of unvaccinated institutionalized residents. Zanamivir had an
      acceptable safety profile in elderly, high-risk LTCF residents and was not
      associated with the emergence of resistant strains.

PMID- 16286059
TI  - Comorbidities among Ohio's nursing home residents with diabetes.
AB  - OBJECTIVE: To determine the magnitude of diabetes mellitus among Ohio nursing
      home residents and the comorbid conditions affecting residents with diabetes.
      RESEARCH DESIGN, METHOD, AND SETTINGS: In certified Ohio nursing homes during
      1999, 161,723 residents were eligible for this study because they had been
      admitted for at least 1 day that year, had been assessed using the Centers for
      Medicaid and Medicare's Minimum Data Set instrument, were 21 years old or older,
      and had a known sex and race. Eligible residents with diabetes were compared with
      those without diabetes with respect to comorbidity. RESULTS: The 25% of residents
      diagnosed with diabetes were younger, more often male, and more often black than
      residents without this disorder. Residents with diabetes were also more likely to
      have cardiovascular diseases; visual problems; foot conditions, including missing
      limbs; and kidney failure. Residents with diabetes were less likely to have oral
      problems than residents without diabetes. CONCLUSION: The Minimum Data Set
      instrument identifies important comorbidities among nursing home residents with
      diabetes and allows their disease course to be followed longitudinally. Nursing
      home residents in Ohio, and presumably in other states, bear a heavy burden from
      diabetes and significant comorbidities.

PMID- 16286058
TI  - Differences in diabetes management of nursing home patients based on functional
      and cognitive status.
AB  - OBJECTIVES: To describe practice patterns regarding diabetes management among
      nursing home (NH) physicians and to identify variation in this practice based on
      patient characteristics. DESIGN: Mailed survey. PARTICIPANTS: Nursing home
      physicians from the American Medical Directors Association (AMDA) Foundation Long
      Term Care Research Network (n = 142), as well as other members of AMDA who were
      Certified Medical Directors (CMD) (n = 68) and members who were not CMD certified
      (n = 45). Response rates to the survey were 51%, 33%, and 23%, respectively.
      MEASUREMENTS: Physician and facility characteristics were queried. Responses to
      12 items pertaining to diabetes management and 5 items pertaining to use of
      specific oral diabetes medications were evaluated in the context of 3 different
      patient profiles that reflected different combinations of functional and
      cognitive impairment. Responses were based on the physicians' perception of how
      they manage diabetes under these specified patient profiles. RESULTS: Responses
      from members of the Research Network indicated highly significant variability (P
      < .01) between the 3 patient profiles for all of the 12 management items.
      Ordering a special diet, monitoring lipid panel, and ordering routine
      ophthalmology was less likely for the patient profile with both functional and
      cognitive impairment (P < .01). These differences among the patient profiles for
      these 3 interventions were present in the responses from all 3 categories of
      physicians (Research Network, CMD, and non-CMD members of AMDA). There was no
      statistically significant variability among the 3 patient profiles for any of the
      3 physician groups regarding the likelihood of using of any of the 5 classes of
      oral diabetic medications. Non-CMD physicians were more likely to have less NH
      experience; otherwise, there were no differences among the 3 physician groups.
      CONCLUSIONS: Nursing home physicians appear to alter the approach to diabetes
      management based on the functional and/or cognitive status of the patient. This
      was particularly true for those physicians who were members of the AMDA
      Foundation Research Network. These findings have implications for initiatives
      designed to guide clinical practice as well as efforts by regulatory bodies to
      evaluate appropriate care. Further research is needed to measure the actual
      impact of different approaches to diabetes management on relevant outcomes in
      this population.

PMID- 16286060
TI  - Gastrostomy and jejunostomy placement: the urban hospital perspective pertinent
      to nursing home care.
AB  - OBJECTIVES: In nursing home settings, providers often think that most
      percutaneous endoscopic gastrostomy (PEG) tubes are placed in older people, some
      perhaps inappropriately. We sought to describe the relationships between patient
      age and the indications for, the decision making behind, and the outcomes of
      gastrostomy and jejunostomy placement in an urban hospital to give perspective to
      those of us working in long-term care settings. DESIGN: Retrospective,
      observational study. SETTING: Urban hospital. PARTICIPANTS: Two hundred thirty
      nine inpatients who underwent gastrostomy or jejunostomy (G/J) placement.
      MEASUREMENTS: Hospital records were reviewed for patient demographics, disease
      process, decision making, and short-term outcomes associated with G/J placement.
      Mortality at 30 days and 1 year was obtained by a search of the National Death
      Index. The prevalence of these variables in those aged 65 years and older was
      compared to the prevalence in those younger than 65 with associations calculated
      both unadjusted and adjusted for gender, place of residence, underlying
      condition, and Charlson comorbidity index. RESULTS: Patients who were aged 65
      years and older were more likely to be female with more comorbid illnesses and
      were more likely to have had a stroke that precipitated their difficulty eating.
      They were more likely to have been referred by a medical specialist, to have been
      seen by a speech pathologist, and to have had their procedure without general
      anesthesia. The older patients had a shorter mean hospital length of stay with
      fewer complications but had higher mortality rates at 30 days and 1 year.
      CONCLUSION: Patient age was associated with gender and type of disease process
      and may have influenced the decisions made during the hospital stay. Despite a
      higher burden of chronic illness, older patient age was not associated with
      adverse short-term outcomes but was associated with higher mortality rates after
      discharge.

PMID- 16286061
TI  - Geriatric versus non-geriatric approach of care to moderate Pra risk senior
      population.
AB  - A total of 432 members of Senior Dimensions, a second-generation social health
      maintenance organization, residing in northern Nevada were identified as moderate
      risk by P(ra) screening criteria for the time period of July 1, 2002, through
      June 30, 2003. Of these members, 166 were impaneled to a practice that only
      provides care for seniors (age 65 years or older), Geriatric Care of Nevada
      (GCN), and 266 members were impaneled to multiple primary care providers with
      standard community-based practices (non-GCN). An annualized cost comparison per
      unit of service provided as derived from the adjusted use data showed an average
      savings of $760.00 per member per year for the GCN over the non-GCN population.
      These savings have occurred apart from the provider fee reimbursement. This
      represents a potential savings of more than $760,000.00 per year per 1000
      moderate P(ra) risk members within a Medicare managed care program.

PMID- 16286062
TI  - Life-threatening, preventable hyperkalemia in a nursing home resident: case
      report and literature review.
AB  - A 70-year-old male nursing home resident, hospitalized for weakness and lethargy,
      was found to have life-threatening hyperkalemia. Concomitant use of potassium
      chloride, spironolactone, and propranolol appeared the likely offending agents.
      Hyperkalemia is common in the elderly, resulting from a combination of potassium
      homeostasis disorders, disease processes and certain medications. In particular,
      older adults in the nursing home on spironolactone and potassium replacement
      preparations should have serum potassium monitored frequently, particularly in
      the presence of renal insufficiency and diabetes. Also included is a review of
      literature illustrating alterations in potassium regulation in older adults and a
      suggested approach to potassium-related disorders in the nursing home setting.

PMID- 16286063
TI  - Combination drug therapy.

PMID- 16286064
TI  - The roles and responsibilities of the nursing home medical director.

PMID- 16286066
TI  - Roles and responsibilities of the medical director in the nursing home: position
      statement A03.

PMID- 16286067
TI  - Cholinesterase inhibitors and anticholinergic drugs: is the pharmacologic
      antagonism myth or reality?

PMID- 16286068
TI  - The cost of being excluded: impact of excluded medications under Medicare part D
      on nursing home residents.

PMID- 16286069
TI  - Culture and sensitivity of infected chronic wounds.

PMID- 16286070
TI  - Misleading cases.

PMID- 16286072
TI  - Regulation of psychopharmacological medications in nursing homes.

PMID- 16286073
TI  - Professional liability in long-term care: the pressure mounts.

PMID- 16286074
TI  - The potential value of negative studies.

PMID- 16286076
TI  - Local environmental effects on the structure of the prion protein.
AB  - Prion diseases are neurodegenerative diseases causally linked to the partial
      unfolding and subsequent misfolding and aggregation of the prion protein (PrP).
      While most proteins fold into a single low energy state, PrP can fold into two
      distinct isoforms. In its innocuous state, denoted as PrPC, the protein has
      predominantly alpha-helical secondary structure, however, PrPC can misfold into
      an isoform rich in extended structure capable of forming toxic and infectious
      aggregates. While prion disease is believed to be a protein-only disease, one not
      requiring any non-protein elements for propagation, the different environments
      the protein finds itself in vivo likely influence its ability to misfold and
      aggregate. In this review we will examine various molecules, covalent
      modifications and environments PrP faces in vivo and the effect they have on
      PrP's local environment and, potentially, conformation. Included in this
      discussion are: (1) pH, (2) carbohydrates, (3) lipid membranes, (4) metal ions,
      and (5) small molecules.

PMID- 16286077
TI  - Translational regulation during oogenesis and early development: the cap-poly(A)
      tail relationship.
AB  - Metazoans rely on the regulated translation of select maternal mRNAs to control
      oocyte maturation and the initial stages of embryogenesis. These transcripts
      usually remain silent until their translation is temporally and spatially
      required during early development. Different translational regulatory mechanisms,
      varying from cytoplasmic polyadenylation to localization of maternal mRNAs, have
      evolved to assure coordinated initiation of development. A common feature of
      these mechanisms is that they share a few key trans-acting factors. Increasing
      evidence suggest that ubiquitous conserved mRNA-binding factors, including the
      eukaryotic translation initiation factor 4E (eIF4E) and the cytoplasmic
      polyadenylation element binding protein (CPEB), interact with cell-specific
      molecules to accomplish the correct level of translational activity necessary for
      normal development. Here we review how capping and polyadenylation of mRNAs
      modulate interaction with multiple regulatory factors, thus controlling
      translation during oogenesis and early development.

PMID- 16286078
TI  - Protein variety and functional diversity: Swiss-Prot annotation in its biological
      context.
AB  - We all know that the dogma 'one gene, one protein' is obsolete. A functional
      protein and, likewise, a protein's ultimate function depend not only on the
      underlying genetic information but also on the ongoing conditions of the cellular
      system. Frequently the transcript, like the polypeptide, is processed in multiple
      ways, but only one or a few out of a multitude of possible variants are produced
      at a time. An overview on processes that can lead to sequence variety and
      structural diversity in eukaryotes is given. The UniProtKB/Swiss-Prot protein
      knowledgebase provides a wealth of information regarding protein variety,
      function and associated disorders. Examples for such annotation are shown and
      further ones are available at http://www.expasy.org/sprot/tutorial/examples_CRB.

PMID- 16286079
TI  - [Side effects of low serum lithium concentrations on renal, thyroid, and sexual
      functions in male and female rats].
AB  - The present study, carried out in rats, is a contribution to explore
      physiological mechanisms underlying lithium toxicity. Male and female mature rats
      were divided into three groups and fed on commercial pellets: group (C) was
      control, group (Li1) was given 2000 mg lithium carbonate/kg of food, and group
      (Li2) was given 4000 mg lithium carbonate/kg of food. If we take into account the
      BW of the rats and the quantity of food they eat every day, we can estimate that
      the quantities of lithium carbonate ingested per day and kilogram of BW are,
      respectively, for the groups Li1 and Li2, of 212 mg (5,738 mmol Li) and 323 mg
      (8,742 mmol Li) for the males, and about 190 mg (5,142 mmol Li) and 289 mg (7,822
      mmol Li) for the females. After 7, 14, 21 and 28 days, serum concentrations of
      lithium, creatinine, free triiodothyronine (FT3) and thyroxine (FT4),
      testosterone and estradiol were measured. Attention was also paid to growth rate
      and a histological examination of testes or vaginal mucosa was carried out. In
      treated rats, a dose-dependent loss of appetite and a decrease in growth rate
      were observed together with polydipsia, polyuria, and diarrhoea. Lithium serum
      concentrations were found to increase from 0.44 mM (day 7) to 1.34 mM (day 28) in
      Li1 rats and from 0.66 to 1.45 mM (day 14) in Li2 rats. Treatment was stopped at
      day 14 in Li2 rats because of a high mortality. The significant increase of
      creatinine that appeared, respectively, at day 7 and 14 in Li2 and Li1 rats shows
      that serum lithium concentrations ranging from 0.62 to 0.75 mM were able to
      induce renal insufficiency, secondarily leading to a time-dependent rise in
      lithium serum concentrations. A significant decrease of serum thyroxine (FT4) and
      triiodothyronine (FT3) levels was observed for lithium concentrations ranging
      from: 0.66 to 0.75 mmol l(-1) (Li2 rats) to 1.27 mmol l(-1) (Li1 rats). This
      effect was more pronounced for FT3, suggesting a defect of FT4/FT3 conversion.
      Under lithium treatment, the testosterone level decreased and spermatogenesis was
      stopped. By contrast, in treated female rats, estradiol level was found to be
      increased in a dose-dependent manner and animals were blocked in the diestrus
      phase at day 28. These results show that lithium can rapidly induce toxic effects
      in the rat at concentrations used for the treatment of bipolar disorders in
      human.

PMID- 16286080
TI  - Decrease of fluctuating asymmetry among larval instars in an aquatic,
      holometabolous insect.
AB  - The use of fluctuating asymmetry (FA) to reveal environmental stress in natural
      populations has been investigated extensively over the past decade. In aquatic
      ecosystems, many investigations involve amphibiotic insects with larval
      development stages in freshwater. To explain the important variability in study
      results, we investigated the FA level of a natural Hydropsyche exocellata
      (Insecta: Trichoptera) population at four different stages, from first larval
      instar to adult. The level of FA decreased between larval stages, but remained
      constant between the last larval instar and the adult. The presence of a
      compensational growth mechanism and the elimination of asymmetric individuals by
      natural selection are two hypotheses that could explain this observation.

PMID- 16286081
TI  - Impact of water deficit intensity on durum wheat seminal roots.
AB  - Experiments were performed under controlled conditions to study seminal roots
      traits of durum wheat genotypes grown under four water conditions. Seminal root
      length, root-to-shoot dry matters ratio and piliferous layer cell size were
      measured. Root volume was assessed at three soil depths. Water stress has
      affected significantly root traits and piliferous layer cell size and this impact
      depends on its intensity. Severe water stress reduced markedly root traits. Water
      treatment by genotype interaction was observed. Middle-East genotypes responded
      differently from Algerian ones. Our results and those obtained elsewhere on the
      same genotypes for other physiological traits are discussed.

PMID- 16286082
TI  - Morphological specificity of yeast and filamentous Candida albicans forms on
      surface properties.
AB  - Physicochemical surface properties of Candida albicans were assessed from
      microbial adhesion to human epithelial cells and to octane droplets. The
      adherence of cells demonstrated the occurrence of morphological specificity for
      these adhesion assays. Filamentous forms exhibited adherence third times higher
      compared to budding forms, while their electrophoretic mobilities were
      comparable. Force measurements performed on filamentous form by AFM demonstrated
      that such adhesion was associated with microfibrillar surface structure.

PMID- 16286083
TI  - [Nomenclature of wood-inhabiting groups in forest entomology: synthesis and
      semantic adjustments].
AB  - The terminology of ecological groups in saproxylic insects (organisms depending
      on dying or dead wood) is used ambiguously by forest entomologists. We therefore
      propose a standardized typology of wood-eating groups, based on two crossed
      factors, i.e. nature and physiological status of woody tissues. We define primary
      and secondary xylophagous insects (corticiphagous, cambiophagous, xylemophagous),
      as well as saproxylophagous species. Insects indirectly related to dead wood are
      classified according to (i) the food regime: consumers of wood-associated
      resources (xylomycophagous, xylomycetophagous, opophagous), commensals
      (scavengers), predators, or (ii) the microhabitat users (fongicolous, cavicolous,
      succicolous).

PMID- 16286084
TI  - Humicolous buthoid scorpions: a new species from Brazilian Amazon.
AB  - A new species of humicolous buthid scorpion is described on the basis of a single
      specimen collected in the Brazilian Amazonia. New considerations on the taxonomy
      and biogeography of some micro-scorpions of the subfamily Ananterinae Pocock,
      1900 are proposed in relation to their possible evolution from endogeous to
      epygean environments.

PMID- 16286085
TI  - Uselessness and indirect negative effects of an insecticide on rice field
      invertebrates.
AB  - Macro-invertebrate assemblages on organic and conventional rice fields were
      quantitatively compared in the Camargue (Rhone delta, France). There was no major
      difference in family richness, but significant differences as regard to
      abundance. Fipronil, the insecticide used to control chironomid larvae, was one
      of the main factors explaining those differences. Its negative impact on
      predatory invertebrates appears to explain the paradoxical lack of difference in
      chironomid abundance between organic and conventional fields, observed during the
      study. Macro-invertebrate biomass estimation showed that, for some birds such as
      herons, conventional rice fields offered a lower value as foraging habitats than
      organic ones.

PMID- 16286086
TI  - Impact of the longitudinal and seasonal changes of the water quality on the
      benthic macroinvertebrate assemblages of the Andorran streams.
AB  - The ecological quality of the Andorran streams was assessed in 1998-1999, based
      on the survey of the water chemistry and the benthic macroinvertebrate
      assemblages. Two types of modification of the water quality were observed in the
      Andorran rivers: (i) a progressive degradation along the longitudinal gradient
      with a chronic degradation in the lower water courses; (ii) a seasonal
      modification in the mid-elevation sites. Two responses of the benthic
      macroinvertebrate assemblages to these disturbances were observed: an extreme
      simplification of the composition and a change of the trophic structure of the
      assemblages in the more impacted sites.

PMID- 16286087
TI  - [Structure and bioassessment of benthic communities of a lagoonal ecosystem of
      the Atlantic Moroccan coast].
AB  - The Merja Zerga lagoon is a semi-enclosed marine ecosystem in which various types
      of human activities have been developed. This paper characterizes the
      biosedimentary units of the lagoon and defines a reference status of the quality
      and health of the macrozoobenthic communities that can be used as bioindicators
      of the quality of the global marine environment. Specific and functional
      diversity were high: 147 taxa were identified; they were distributed within seven
      main trophic groups. Trophic structure is dominated by the suspension-feeding
      bivalve Cerastoderma edule and the deposit-feeding bivalve Scrobicularia plana,
      while micrograzers and macroherbivores remain low. Biotic index values indicated
      that the site is moderately perturbed and that the benthic communities are
      unbalanced. Nevertheless, the communities showed a seasonal stability of
      abundances and a high specific richness all through the year.

PMID- 16286088
TI  - [Temporal variations of physicochemical and microbiological parameters in three
      freshwater ecosystems (southeastern France) invaded by Ludwigia spp].
AB  - In France, two amphibious hydrophytes of alien Ludwigia (Onagraceae) have for
      about the past twenty years been causing serious ecological and economic
      problems: L. peploides (Kunth) Raven et L. grandiflora (Michaux) Greuter &
      Burdet. This bacteriological and physicochemical study, focused on three
      different Mediterranean aquatic ecosystems, reveals, for the first time, a direct
      negative impact of these American invaders. During summer, while plant growth is
      intensive, and the appearance in the water column of anoxic conditions and
      production of toxic compounds may be observed, notably in L. grandiflora stands.
      The toxicity is linked to a proliferation of sulphate-reducing bacteria producing
      sulphides that are very harmful for aquatic organisms.

PMID- 16286090
TI  - Phylogenetic relationships and biodiversity in Hylids (Anura: Hylidae) from
      French Guiana.
AB  - We evaluated two biodiversity criteria, higher taxonomic diversity and
      phylogenetic diversity in French Guiana. For this, we used a recent assessment of
      the knowledge accumulated since 30 years of study on the amphibian species
      currently known in French Guiana. We focused on two well-represented genera, Hyla
      and Scinax, belonging to the subfamily Hylinae. We used partial sequences of two
      mitochondrial genes (16S rDNA and 12S rDNA, 813 bp) and two nuclear genes
      (tyrosinase and 18S rRNA, 1590 bp) covering a total of 2403 bp. According to the
      high bootstrap support in phylogenetic analysis of the complete dataset, the
      genus Scinax is a homophyletic clade formed by two species groups (rubra and
      rostrata) in French Guiana. The genus Hyla was confirmed to be a paraphyletic
      group formed by two species groups as well (30 chromosomes and the 'gladiator
      frogs'). We confirmed that these genera should be taxonomically reconsidered.
      Moreover, at the genus, subfamily and family levels, the use of only
      morphological characters or only molecular DNA markers would hamper estimations
      of biodiversity. Thus, we strongly advise the combined use of both morphology and
      molecular data (nuclear and mitochondrial markers).

PMID- 16286089
TI  - The phylogeny of squamate reptiles (lizards, snakes, and amphisbaenians) inferred
      from nine nuclear protein-coding genes.
AB  - Squamate reptiles number approximately 8000 living species and are a major
      component of the world's terrestrial vertebrate diversity. However, the
      established relationships of the higher-level groups have been questioned in
      recent molecular analyses. Here we expand the molecular data to include DNA
      sequences, totaling 6192 base pairs (bp), from nine nuclear protein-coding genes
      (C-mos, RAG1, RAG2, R35, HOXA13, JUN, alpha-enolase, amelogenin and MAFB) for 19
      taxa representing all major lineages. Our phylogenetic analyses yield a largely
      resolved phylogeny that challenges previous morphological analyses and requires a
      new classification. The limbless dibamids are the most basal squamates. Of the
      remaining taxa (Bifurcata), the gekkonids form a basal lineage. The Unidentata,
      squamates that are neither dibamids nor gekkonids, are divided into the
      Scinciformata (scincids, xantusiids, and cordylids) and the Episquamata
      (remaining taxa). Episquamata includes Laterata (Teiformata, Lacertiformata, and
      Amphisbaenia, with the latter two joined in Lacertibaenia) and Toxicofera
      (iguanians, anguimorphs and snakes). Our results reject several previous
      hypotheses that identified either the varanids, or a burrowing lineage such as
      amphisbaenians or dibamids, as the closest relative of snakes. Our study also
      rejects the monophyly of both Scleroglossa and Autarchoglossa, because Iguania, a
      species-rich lineage (ca. 1440 sp.), is in a highly nested position rather than
      being basal among Squamata. Thus iguanians should not be viewed as representing a
      primitive state of squamate evolution but rather a specialized and successful
      clade combining lingual prehension, dependence on visual cues, and ambush
      foraging mode, and which feeds mainly on prey avoided by other squamates.
      Molecular time estimates show that the Triassic and Jurassic (from 250 to 150
      Myr) were important times for squamate evolution and diversification.

PMID- 16286091
TI  - The predatory behaviour of a tramp ant species in its native range.
AB  - Workers of the pest ant Paratrechina longicornis participate in a type of group
      hunting. Each individual forages with its long antennae wide open and moves
      quickly (6.3 cm/s) along an erratic path surrounded by nestmates behaving in the
      same way and within range of a recruiting pheromone. They detect prey by contact
      with successful workers singly capturing and retrieving small prey and seizing
      larger ones by an appendage. Then they recruit nestmates at short-range; all
      together they spread-eagle the prey and retrieve them whole.

PMID- 16286092
TI  - Amyloid fibril formation by macrophage migration inhibitory factor.
AB  - We demonstrate herein that human macrophage migration inhibitory factor (MIF), a
      pro-inflammatory cytokine expressed in the brain and not previously considered to
      be amyloidogenic, forms amyloid fibrils similar to those derived from the disease
      associated amyloidogenic proteins beta-amyloid and alpha-synuclein. Acid
      denaturing conditions were found to readily induce MIF to undergo amyloid fibril
      formation. MIF aggregates to form amyloid-like structures with a morphology that
      is highly dependent on pH. The mechanism of MIF amyloid formation was probed by
      electron microscopy, turbidity, Thioflavin T binding, circular dichroism
      spectroscopy, and analytical ultracentrifugation. The fibrillar structures formed
      by MIF bind Congo red and exhibit the characteristic green birefringence under
      polarized light. These results are consistent with the notion that amyloid fibril
      formation is not an exclusive property of a select group of amyloidogenic
      proteins, and contribute to a better understanding of the factors which govern
      protein conformational changes and amyloid fibril formation in vivo.

PMID- 16286093
TI  - A quantitative matrigel assay for assessing repopulating capacity of prostate
      stem cells.
AB  - Homeostasis of prostate tissue is maintained by stem cells, although such cells
      have not been well characterized. Here, we report establishment of such a method
      using matrigel. Matrigel containing a single-cell suspension from adult prostatic
      cells was subcutaneously grafted into the flank of nude mice. Prostatic duct-like
      structures derived from donor tissue were observed in the gel 2 weeks after
      transplantation. Luminal and basal cells observed in the gel expressed several
      markers characteristic of prostatic and/or epithelial cells. When a mixture with
      both EGFP-positive and negative prostate cells was transplanted, prostatic ducts
      consisted of either EGFP-positive or negative cells and chimeric patterns were
      rarely observed, suggesting that ducts were reconstituted from a single cell.
      Stem cell number and function were also evaluated by competition with control
      cells. Overall this method revealed that cells localized in the proximal portion
      in prostate ducts had higher reconstitution capacity than those in the distal
      portion. We conclude that prostate stem/progenitor cells exist and that our
      method is applicable to analysis of prostate stem cells, epithelial mesenchyme
      interactions, and prostate cancer stem cells.

PMID- 16286095
TI  - Non-muscle-invasive bladder cancer: the role of radical cystectomy.

PMID- 16286094
TI  - Doping in the recombinant era: strategies and counterstrategies.
AB  - Advances in recombinant DNA technology have created one of the most powerful
      weapons in the current doping arsenal: recombinant proteins [Sweeney HL. Gene
      doping. Sci Am 2004;291:62-9; Unal M, Ozer Unal D. Gene doping in sports. Sports
      Med 2004;34:357-62]. Recombinant erythropoietin (EPO) and human growth hormone
      (hGH) are currently being abused but are fortunately detectable either directly
      by employing isoelectric focusing and immunoassays or indirectly by assessing
      changes in selected hematopoietic parameters. The detection is technically
      demanding due to the extent of similarity between the recombinant proteins and
      their endogenous counterparts. Another issue facing detection efforts is the
      speed and conditions at which blood samples are collected and analyzed in a
      sports setting. Recently, gene doping, which stemmed out of legitimate gene
      therapy trials, has emerged as the next level of doping. Erythropoietin (EPO),
      human growth hormone (hGH), insulin-like growth factor-1 (IGF-1), peroxisome
      proliferator-activated receptor-delta (PPAR delta), and myostatin inhibitor genes
      have been identified as primary targets for doping. Sports clinical scientists
      today are racing against the clock because assuring the continued integrity of
      sports competition depends on their ability to outpace the efforts of dopers by
      developing new detection strategies.

PMID- 16286096
TI  - Management of erectile dysfunction after radical prostatectomy.

PMID- 16286097
TI  - Effects of long-term finasteride treatment on prostate cancer morphology and
      clinical outcome.
AB  - OBJECTIVES: To examine the morphologic alterations of finasteride therapy on
      prostate cancer compared with no treatment or treatment with a luteinizing
      hormone-releasing hormone (LHRH) agonist and the clinical outcomes of patients
      treated with finasteride. METHODS: The data of 56 patients with prostate cancer
      who had taken finasteride for at least 6 months were reviewed. A central
      pathology review was performed in a blinded manner comparing these patients with
      56 matched controls and 44 patients who received a 3-month course of LHRH agonist
      before radical prostatectomy. The histologic hormonal treatment effects included
      apoptosis, vacuolated cytoplasm, pyknotic nuclei, and small irregular glands. An
      overall consensus was scored using a three-tiered system: no apparent effect
      (score = 0), suspicious for hormonal effect (score = 1), and highly suggestive of
      hormonal treatment (score = 2). A Gleason score was assigned to all prostatectomy
      specimens. RESULTS: The mean hormonal treatment score for the prostatectomy
      specimens was 0.4, 0.5, and 1.6 for the control, finasteride, and 3-month LHRH
      groups, respectively. Surprisingly, 20% of control patients had suspicious or
      highly suggestive hormonal effects and 26% of the finasteride-treated patients
      did so. For the LHRH-treated group, only 23% did not demonstrate classic features
      of hormonal treatment. Similar clinical outcomes were observed between the
      finasteride and control groups. CONCLUSIONS: No consistent hormonal therapy
      effects with finasteride treatment were observed compared with LHRH agonists. The
      hormonal effect was observed in the control group. Therefore, although other
      aspects of the Prostate Cancer Prevention Trial design might account for the
      greater percentage of Gleason grade tumors in the study arm, morphologic changes
      due to long-term finasteride treatment were not a likely cause.

PMID- 16286098
TI  - Prevalence, diagnosis, characterization, and treatment of prostatitis,
      interstitial cystitis, and epididymitis in outpatient urological practice: the
      Canadian PIE Study.
AB  - OBJECTIVES: To determine the prevalence, diagnostic patterns, and management of
      prostatitis, interstitial cystitis, and epididymitis (PIE) in Canadian urology
      outpatient practice. METHODS: Representative urologists were randomly selected
      from the Canadian and Quebec Urological Associations. Each patient identified
      with a PIE diagnosis during a typical 2-consecutive-week period during April 2004
      to July 2004 was requested to complete a corresponding Chronic Prostatitis
      Symptom Index (CPSI), O'Leary-Sant Symptom Index (OSSI), or a Chronic
      Epididymitis Symptom Index (CESI). Each day the participant urologist completed
      an outpatient log and a detailed programmed chart review to transcribe
      demographics, investigations, and treatments associated with each PIE patient.
      RESULTS: Sixty-five urologists were invited to participate. Fifty-seven (88%)
      agreed, and 48 (74%) completed the audit. Of the 8712 patients seen in outpatient
      practice (average 182 per urologist), 2675 were female and 6037 male. Prostatitis
      was identified in 2.7% of the men (n = 166; mean age 50 years; mean duration 3.1
      years; mean CPSI score 19.7), interstitial cystitis in 2.8% of patients (n = 242;
      211 women [7.9%], 26 men [0.4%]; mean age 50.2 years, mean duration 4.5 years,
      mean OSSI score 11.8), and epididymitis in 0.9% of men (n = 57; mean age 41.1
      years, mean duration 2.5 years, mean CESI score 15.5). There was wide variance in
      investigations and treatments. CONCLUSIONS: This prospective audit indicates that
      prostatitis might not be as common as frequently believed and that interstitial
      cystitis is more common, and it represents the first estimate of the prevalence
      of epididymitis in urologic practice. The wide variance in investigations and
      treatments confirms the need for practice management guidelines.

PMID- 16286099
TI  - Shock wave lithotripsy success determined by skin-to-stone distance on computed
      tomography.
AB  - OBJECTIVES: To evaluate whether the skin-to-stone distance (SSD), body mass index
      (BMI), and Hounsfield unit (HU) density can be used as independent predictors of
      stone-free (SF) status after shock wave lithotripsy (SWL) of lower pole kidney
      stones. No studies have evaluated the SSD by non-contrast-enhanced computed
      tomography (NCCT) as a predictor of SWL success. Studies have suggested that the
      BMI and HU density of urinary calculi on NCCT may predict the SF rate after SWL.
      METHODS: The radiographs of 64 patients treated with SWL (DoliS lithotripter)
      from March 2000 to April 2004 with lower pole kidney stones measuring 0.5 to 1.5
      cm on NCCT were reviewed. The average SSD was calculated by measuring three
      distances from the center of the stone to the skin (0 degrees, 45 degrees, and 90
      degrees angles) on NCCT. The BMI and HU density were determined, and chemical
      analysis was performed on all stones. Radiographic assessment of the kidneys,
      ureter, and bladder at 6 weeks categorized patients into the SF or residual stone
      group. Logistic regression was fit, using SSD, BMI, and HU density as predictors,
      to assess the SF rates after SWL. RESULTS: Of 64 patients, 30 were SF and 34 had
      residual stones. The mean SSD was 8.12 +/- 1.74 cm for the SF group versus 11.53
      +/- 1.89 cm for the residual stone group (P <0.01). Logistic regression analysis
      revealed only SSD to be a significant predictor of outcome (odds ratio 0.32, 95%
      confidence interval 0.29 to 0.35, P <0.01). An SSD greater than 10 cm predicted
      treatment failure. CONCLUSIONS: The SSD may predict the outcome after SWL of
      lower pole kidney stones. SWL in patients with an SSD greater than 10 cm is
      likely to fail. The use of the SSD may be transferable to the treatment of all
      urinary stones, regardless of location.

PMID- 16286100
TI  - Role of tamsulosin in treatment of patients with steinstrasse developing after
      extracorporeal shock wave lithotripsy.
AB  - OBJECTIVES: To evaluate whether tamsulosin, as an alpha(1)-blocker, was effective
      for the treatment of steinstrasse in the lower ureter after shock wave
      lithotripsy. METHODS: A total of 67 patients (43 men and 24 women) with
      steinstrasse in the lower portion of the ureters were randomly divided into two
      groups. Only hydration and tenoxicam (20 mg orally once daily) was given to group
      1 (35 patients). Group 2 (32 patients), was also given tamsulosin (0.4 mg daily).
      All patients were reevaluated and questioned about the number of episodes and
      severity of ureteral colic and the rates of spontaneous resolution of
      steinstrasse 6 weeks after beginning treatment. They were asked to score the
      severity of pain according to a visual analog scale. RESULTS: In 23 (65.7%) of 35
      patients in group 1 and in 24 (75%) of 32 patients in group 2, steinstrasse
      resolved during the first 6 weeks. The resolution rates were not significantly
      different (P >0.05) between groups 1 and 2. Group 1 had more ureteral colic
      episodes than did group 2 while passing their stones. This difference was
      statistically significant (P <0.01). Group 1 patients reported significantly
      greater (P <0.001) visual analog scale scores than did group 2 patients.
      CONCLUSIONS: The addition of tamsulosin to conservative treatment seemed to be
      beneficial in terms of the reduced number of ureteral colic episodes and the
      severity of pain in the patients who developed steinstrasse after shock wave
      lithotripsy.

PMID- 16286101
TI  - Anatomy of pudendal nerve at urogenital diaphragm--new critical site for nerve
      entrapment.
AB  - OBJECTIVES: To investigate the relations of the pudendal nerve in this complex
      anatomic region and determine possible entrapment sites that are accessible for
      surgical decompression. Entrapment neuropathies of the pudendal nerve are an
      uncommon and, therefore, often overlooked or misdiagnosed clinical entity. The
      detailed relations of this nerve as it exits the pelvis through the urogenital
      diaphragm and enters the mobile part of the penis have not yet been studied.
      METHODS: Detailed anatomic dissections were performed in 10 formalin preserved
      hemipelves under 3.5x loupe magnification. The pudendal nerve was dissected from
      the entrance into the Alcock canal to the dorsum of the penis. The branching
      pattern of the nerve and its topographic relationship were recorded and
      photographs taken. RESULTS: The anatomic dissections revealed that the pudendal
      nerve passes through a tight osteofibrotic canal just distal to the urogenital
      diaphragm at the entrance to the base of the penis. This canal is, in part,
      formed by the inferior ramus of the pubic bone, the suspensory ligament of the
      penis, and the ischiocavernous body. In two specimens, a fusiform
      pseudoneuromatous thickening was found. CONCLUSIONS: The pudendal nerve is
      susceptible to compression at the passage from the Alcock canal to the dorsum of
      the penis. Individuals exposed to repetitive mechanical irritation in this region
      are especially endangered. Diabetic patients with peripheral neuropathy can have
      additional compression neuropathy with decreased penile sensibility and will
      benefit from decompression of the pudendal nerve.

PMID- 16286102
TI  - One-step percutaneous nephrolithotomy sheath versus standard two-step technique.
AB  - OBJECTIVES: Advances in technique and equipment have allowed urologists to
      perform percutaneous stone removal with increasing efficacy and decreasing
      complications. The procedure of choice for large renal calculi is percutaneous
      nephrolithotomy. At our institution, percutaneous access is achieved by a two
      step process using either Amplatz dilators or placement of a high-pressure
      balloon catheter for tract dilation, followed by advancement of a sheath over the
      balloon. A novel device, the Pathway Access Sheath (PAS) has been developed that
      allows for balloon tract dilation and percutaneous access sheath placement in one
      simple step. METHODS: Our study population consisted of 21 patients, who were
      randomized to one of two arms. Of the 21 patients, 10 underwent standard two-step
      access using a high-pressure balloon catheter and 11 underwent percutaneous
      nephrolithotomy using the novel PAS. We compared the insertion time, blood loss,
      and cost between the two techniques. RESULTS: The average insertion time was
      shorter in the PAS group (3 minutes) compared with the high-pressure balloon
      catheter (5 minutes, 42 seconds); a difference that was statistically significant
      (P <0.01). The estimated blood loss and cost were similar between the two groups.
      The increased sheath flexibility of the PAS was noted to be an advantage in some
      patients. CONCLUSIONS: The results of our study have shown that a novel single
      step renal access device is safe and efficacious and results in a shorter
      insertion time for percutaneous nephrolithotomy. Blood loss was less in the PAS
      group as well, although the difference was not statistically significant.
      Additional studies will establish whether this device will provide a new standard
      of obtaining renal access.

PMID- 16286103
TI  - Location and etiology of flexible and semirigid ureteroscope damage.
AB  - OBJECTIVES: To perform an analysis of currently available manufacturer data
      regarding the character of ureteroscope damage. The high costs associated with
      the repair of flexible and semirigid ureteroscopes are well documented. Increased
      knowledge of the etiology of ureteroscope damage should aid urologists in
      prolonging the lives of these delicate instruments. METHODS: We requested data
      from the four major ureteroscope manufacturers (ACMI, Olympus America, Karl
      Storz, and Richard Wolf) on the types, speculated causes, costs, and frequency of
      ureteroscope damage. The results were tabulated in a blinded fashion and analyzed
      for trends. We then formulated guidelines that could be applied by practicing
      urologists. RESULTS: For both flexible and semirigid ureteroscopes, the frequency
      of repair increased with decreasing ureteroscope diameter and increasing
      instrument length. The cost of the repair was generally greater for flexible
      ureteroscopes (mean 4597 dollars) than for semirigid ureteroscopes (mean 2437
      dollars). The major causes of flexible ureteroscope damage were working channel
      damage from laser burn or instrument passage and extreme scope deflection with an
      indwelling instrument. The primary reasons for semirigid ureteroscope repair
      included overtorquing and improper handling in the operating room and during
      sterile processing. CONCLUSIONS: Urologists can minimize the repair costs of
      flexible and semirigid ureteroscopes by taking precautions to eliminate laser
      fiber-induced damage and by avoiding overdeflection. Improved storage and
      handling of these instruments is also necessary. Although small-diameter
      ureteroscopes are favorable because of their increased mobility and ease of
      passage, physician and staff awareness of their increased fragility is vital in
      maximizing the longevity of these commonly used instruments.

PMID- 16286104
TI  - Correlates and prevalence of prostatitis in a large community-based cohort of
      older men.
AB  - OBJECTIVES: To describe the prevalence and correlates of self-reported history of
      prostatitis in terms of lower urinary tract symptoms and associated
      dissatisfaction in community-dwelling older men. METHODS: We performed a cross
      sectional analysis from a prospective cohort study of 5821 men aged 65 years and
      older recruited from six clinical centers. RESULTS: Overall, 1439 men (25%) self
      reported a history of prostatitis. Men with a history of prostatitis were more
      likely to self-report a history of prostate cancer (26% versus 7%; P < 0.0001)
      and a history of benign prostatic hyperplasia (83% versus 38%; P < 0.0001) within
      a lifetime compared with men without a history of prostatitis. Men with a history
      of prostatitis also had a greater mean American Urological Association symptom
      score (mean +/- SD, 10.1 +/- 7.1 versus 7.7 +/- 5.9; P < 0.0001) than men without
      a history of prostatitis. Also, a greater percentage of men with a history of
      prostatitis reported being dissatisfied with their present urinary condition than
      did men without a history of prostatitis (21% versus 11%; P < 0.0001). We found
      positive associations for a history of prostatitis with a history of benign
      prostatic hyperplasia (odds ratio 8.0, 95% confidence interval 6.8 to 9.5), a
      history of prostate cancer (odds ratio 5.4, 95% confidence interval 4.4 to 6.6),
      and dissatisfaction with current urinary condition (odds ratio 1.2, 95%
      confidence interval 1.01 to 1.5). CONCLUSIONS: A self-reported history of
      prostatitis is common in older men and was associated with self-reported prostate
      cancer and benign prostatic hyperplasia and increased severity of lower urinary
      tract symptoms and associated dissatisfaction. Because of the potential detection
      bias, recall bias, and the cross-sectional nature of the study, limiting causal
      inference, the associations among these urologic conditions require additional
      study.

PMID- 16286105
TI  - Experience with marginal living related kidney donors: are they becoming routine
      or are there still any doubts?
AB  - OBJECTIVES: To analyze donor and recipient outcome of grafts from marginal kidney
      donors (ie, elderly or suffering from some anomaly). METHODS: We had 81 marginal
      donors from July 1996 to July 2004; 46 were older than 60 years, and 39 had renal
      or nonrenal anomaly. The donors and recipients were evaluated for morbidity,
      graft and recipient survival, and the number of rejection episodes. RESULTS: The
      mean (+/- standard deviation) age of elderly donors was 62.2 +/- 3.1 years.
      Follow-up ranged from 6 months to 50 months (mean 21.15 +/- 0.9 months).
      Actuarial 1-year and 3-year graft survival rates were 95% and 81%, respectively.
      Twenty-six percent of recipients maintained serum creatinine levels less than 1.4
      mg/dL. The mean age of hypertensive donors was 46.2 years, and blood pressure was
      controlled with one drug. Serum creatinine levels in the recipients were less
      than 1.4 mg/dL in 10 and less than 2.5 mg/dL in the rest. Eleven percent of
      hypertensive donors required an increase in their antihypertensive medication.
      All donors showed a 15% to 20% increase in their glomerular filtration rate.
      Donors underwent simultaneous surgery when indicated. CONCLUSIONS: Criteria to
      reject donors need to be reviewed periodically. The elderly and donors with other
      anomalies are consistently showing acceptable results. Hypertensive donors
      require assessment with awake ambulatory blood pressure monitoring.

PMID- 16286106
TI  - Simplifying laparoscopic partial nephrectomy: technical considerations for
      reproducible outcomes.
AB  - OBJECTIVES: To present our technique, modifications, and experience of
      laparoscopic partial nephrectomy (LPN). Nephron-sparing surgery is an
      increasingly accepted treatment for selected T1a kidney tumors. Because of the
      more complex surgical technique involved, LPN is evolving more slowly than
      laparoscopic radical nephrectomy. METHODS: The data of 41 consecutive patients
      with T1a tumors who had undergone LPN from October 2002 to March 2004 were
      retrospectively reviewed. Four main considerations in our surgical technique were
      consistently used: (a) LPN was performed in the transperitoneal approach, (b) a
      suture traction system was placed on the kidney when tumor visualization was
      challenging, (c) sutures and bolsters were preloaded on the abdominal wall, and
      (d) hemostasis and closure of the renal defect was performed using Lapra-Ty
      clips, eliminating knot-tying. RESULTS: The mean patient age was 63.1 years. The
      mean warm ischemia time was 29.7 minutes, and the mean surgical time was 226.5
      minutes. In 26 of 41 patients, the collecting system was entered and repaired.
      The median estimated blood loss was 150 mL, with a mean tumor size of 2.2 cm.
      Three cases were converted to open surgery. Five complications (13.2%) occurred.
      The median hospital stay was 2 days. Of the 41 specimens, 11 were benign. All
      surgical margins were negative. The mean follow-up was 7.5 months. CONCLUSIONS:
      Although technically challenging, LPN is emerging as an alternative to open
      partial nephrectomy. With several easily applied technical considerations, we
      have simplified LPN, making the procedure more efficient. We believe that the
      technical considerations we describe can increase the feasibility and ease of LPN
      for Stage T1a exophytic renal tumors.

PMID- 16286107
TI  - Steps to reduce operative time in laparoscopic dismembered pyeloplasty for
      moderate to large renal pelvis.
AB  - OBJECTIVES: To describe the steps to reduce the operative time for laparoscopic
      dismembered pyeloplasty in ureteropelvic junction obstruction with moderate to
      large hydronephrosis. METHODS: Using a transperitoneal approach and three ports,
      pyelotomy was done proximal to the ureteropelvic junction, and the ureter was
      spatulated laterally before dismembering it. Using the three suture line
      technique, the first suture was taken at the distal end of the spatulated ureter
      outside-in to the most dependent part of the pelvis inside-out and left as such.
      The second suture was taken at the proximal end of the ureter outside-in to the
      corresponding site at the posterior wall of the pelvis and then continued
      distally to complete the posterior suture line. A double-J stent was placed in an
      antegrade way. The anterior wall was completed with the first suture, taking
      continuous bites. The third suture line was used to close the pelvis. The
      operative time was recorded from placing the patient in the lateral position to
      the closure of the last port. RESULTS: From January 2002 to January 2004, 24
      patients underwent pyeloplasty performed by a single surgeon. The mean pelvic
      volume was 80.4 cm3 (range 70 to 110). The mean patient age was 24.5 years (range
      5 to 57). The body mass index was 22.28 kg/m2 (range 20 to 25). The mean
      operative time was 120.4 minutes (range 80 to 160). Minor complications were
      noted in 3 patients. All patients showed improvement in symptoms and drainage
      after a mean follow-up of 17 months (range 10 to 28). CONCLUSIONS: These steps
      helped to reduce the operative time to close to that of open surgery, making
      laparoscopic pyeloplasty a more desirable alternative.

PMID- 16286108
TI  - Extrarenal vascular anatomy of kidney: assessment of variations and their
      relevance to partial nephrectomy.
AB  - OBJECTIVES: To evaluate the feasibility of selective segmental artery clamping
      during partial nephrectomy. METHODS: Precise extraparenchymal renal hilar
      dissection was performed on 73 fixed cadaveric kidneys. The surgical
      accessibility to clamping of each presegmental and segmental artery from the
      anterior and posterior approaches was determined on the basis of vessel length,
      position within the renal hilum, and degree of overlying collecting system or
      venous structures. RESULTS: The vascular anatomy consisted of zero, one, or two
      presegmental arteries (extrarenal main renal artery branches that split into two
      or more segmental arteries) in 49.3%, 31.5%, and 19.2% of the kidneys,
      respectively. From a posterior approach, the posterior segmental artery was
      accessible to isolated clamping in 81.8% of the kidneys (segmental accessibility
      rate) and was accessible to clamping at the presegmental level in 12.7%
      (presegmental accessibility rate) for a total accessibility rate of 90.9%. The
      total accessibility rate for the inferior segmental artery was 88.5% from an
      anterior and 66.7% from a posterior surgical approach. The apical artery total
      accessibility rate was 72.3% and 40.5% from an anterior and posterior approach,
      respectively. The corresponding middle and superior segmental artery total
      accessibility rates were 50.8% and 32.8%. CONCLUSIONS: In this cadaveric model,
      hilar dissection and clamping of the renal segmental arteries is anatomically
      feasible in most cases. Posterior and polar tumors will likely be more amenable
      to segmental vascular control. Selective segmental vascular control may offer the
      benefits of total hilar control while reducing overall renal ischemic injury.

PMID- 16286109
TI  - Ureteroiliac artery fistula: diagnosis and treatment algorithm.
AB  - OBJECTIVES: To review the diagnosis and treatment of ureteroarterial fistulas and
      to develop a management algorithm. Long-term ureteral stenting, along with pelvic
      surgery and radiotherapy, have led to an increased incidence of ureteroarterial
      fistulas. Experience diagnosing and treating these fistulas has been limited to
      case reports. METHODS: A retrospective chart review from 1975 to 2004 revealed
      eight ureteroarterial fistulas in 7 patients at our institution. The patient
      demographics, presenting symptoms, and diagnostic studies were reviewed. Also, we
      analyzed the treatment, hospital course, and long-term outcomes. RESULTS:
      Ureteroarterial fistulas were more common in women (86%) than in men. All
      patients presented with gross hematuria, and 57% had lateralizing flank pain.
      Risk factors included chronic indwelling stents (87%), previous pelvic external
      beam radiotherapy (71%), pelvic surgery (100%), and vascular disease (87%).
      Provocative angiography was diagnostic in only 63% of cases. Although not
      sensitive, cystoscopy revealed lateralized, pulsatile hematuria in all cases when
      performed. Treatment ranged from endovascular stenting with nephrostomy tube to
      primary surgical repair with nephrectomy. CONCLUSIONS: On the basis of this
      review, we propose a systematic diagnostic and treatment approach to a serious
      disease process. The use of these proposed algorithms will minimize unnecessary
      testing, increase the speed of diagnosis, and potentially improve overall
      outcomes of patients with ureteroarterial fistulas.

PMID- 16286110
TI  - Vaginal mesh extrusion associated with use of Mentor transobturator sling.
AB  - OBJECTIVES: To describe my experience of vaginal mesh extrusion using the
      monofilament polypropylene transobturator sling, the Mentor ObTape. The Mentor
      ObTape was the first transobturator sling developed as an alternative to the
      retropubic commercially available suburethral slings for providing mid-urethral
      support as treatment of female stress urinary incontinence. METHODS: Thirty
      patients underwent transobturator suburethral sling placement for anatomic stress
      urinary incontinence using the ObTape from October 2003 to January 2005. A
      retrospective chart review was performed to retrieve data on the safety,
      efficacy, complications, and outcomes using this product. RESULTS: Six patients
      (20%) to date have presented with defective vaginal healing manifested by
      extrusion of the sling material. Five patients required surgical removal of the
      sling material, and one underwent a trial of conservative management. No urethral
      erosions were noted. CONCLUSIONS: In my experience, the Mentor ObTape sling,
      which uses a nonwoven, minimally elastic, micropore, monofilament polypropylene
      mesh, incurs an unacceptably high rate of defective vaginal wound healing and
      mesh extrusion.

PMID- 16286111
TI  - Is catheter cause of subjectivity in sensations perceived during filling
      cystometry?
AB  - OBJECTIVES: To investigate the impact of the catheter on perceptions of filling.
      In our previous study, we demonstrated that some patients perceived sensations
      despite a lack of filling during cystometry. METHODS: The study included 45
      patients with lower urinary tract symptoms attributed to benign prostatic
      hyperplasia. The average patient age was 57.9 years (range 48 to 79). Patients
      were draped to keep them from seeing their penis and the filling bag, pump, and
      screen process. In the first phase, the catheter was fixed to the penile skin
      without introducing it through the urethra, and the patient was told the test had
      begun. At the end of the first phase, the bladder was emptied. Before the second
      phase, an 8F urodynamic catheter was introduced, but during the test, nothing was
      infused. During the third phase, filling cystometry was performed with a 50
      mL/min pump speed. The bladder was emptied after all three phases. The times that
      elapsed until each sensation was perceived, in seconds, were used to compare the
      sensations. RESULTS: In the first phase, 21 patients reported a first sensation,
      10 reported first desire, and 4 reported normal desire, despite a lack of
      catheterization. No statistically significant difference was found between the
      mean first sensation/first desire, first sensation/normal desire, first
      desire/normal desire ratios of the patients who perceived sensations in the three
      phases and the strong desire/normal desire ratios of the patients in the second
      and third phases (P >0.05 for all). CONCLUSIONS: Although the perceptions were
      reported in the first and second phases, the catheter could not be the sole cause
      of the subjectivity.

PMID- 16286113
TI  - Videourodynamic characteristics and lower urinary tract symptoms of female
      bladder outlet obstruction.
AB  - OBJECTIVES: To analyze the lower urinary tract symptoms (LUTS) and
      videourodynamic characteristics of female bladder outlet obstruction (BOO).
      METHODS: Videourodynamic studies were performed in 207 women with signs and
      symptoms of BOO. Bladder outlet obstruction was defined as the radiologic
      evidence of bladder outlet narrowing plus a voiding pressure greater than 35 cm
      H2O and a maximum flow rate less than 15 mL/s or a voiding pressure greater than
      40 cm H2O. Women with BOO were categorized into five groups on the basis of the
      videourodynamic findings. The LUTS and urodynamic parameters were analyzed
      according to these classifications. RESULTS: Videourodynamic study revealed
      bladder neck obstruction in 18 patients (8.7%), urethral sphincter obstruction in
      56 (27.1%), pelvic floor muscle obstruction in 106 (51.2%), high-grade pelvic
      organ prolapse and BOO in 13 (6.3%), and urethral stricture in 14 (6.8%). Urgency
      frequency was reported by 94% and difficult urination by 57% of the total
      patients. Among the 17 patients with urinary retention, obstruction was noted at
      the urethral sphincter in 10, pelvic floor muscle in 5, bladder neck in 1, and
      urethral stricture in 1. Detrusor overactivity was found in 52.7% of total
      patients and was most frequent in those with urethral sphincter obstruction
      (78.6%). Patients with bladder neck obstruction had the highest voiding pressure
      and lowest maximum flow rate. CONCLUSIONS: Differences in videourodynamic
      characteristics of women with BOO might be associated with the underlying
      pathophysiology of the bladder, urethral, and pelvic floor muscle dysfunction.

PMID- 16286115
TI  - Impact of the percentage of positive biopsy cores on the further stratification
      of primary grade 3 and grade 4 Gleason score 7 tumors in radical prostatectomy
      patients.
AB  - OBJECTIVES: To examine whether the percentage of core biopsies positive can
      further stratify Gleason score 7 patients with primary Gleason grade into precise
      prognostic groups. METHODS: Between 1991 and 1999, 379 radical prostatectomy
      patients were found to have pathologic Gleason 7 tumors. The patients were
      divided into primary grade 3 or 4. Percentage positive was calculated by dividing
      the number of positive core biopsies by the total number of cores. RESULTS: In
      the cohort, 290 tumors were primary grade 3, and 89 were primary grade 4. On
      univariate analysis patients with primary grade 3 tumors had a significant
      prostate-specific antigen (PSA) progression-free survival advantage over grade 4
      patients. When separated according to percentage of core biopsies positive,
      statistical analysis revealed significantly better 60-month actuarial PSA
      progression-free survival for patients with grade 3 and grade 4 and less than 50%
      core biopsies positive as compared with grade 3 and grade 4 and 50% or more core
      biopsies positive (85%, 85%, 61%, and 33%, respectively). Furthermore,
      multivariate analysis demonstrated that primary grade did not have an independent
      impact on biochemical progression-free survival. However, on subset analysis,
      among patients with 50% or more biopsy cores positive, primary Gleason grade was
      indeed found to have a significant, independent impact. CONCLUSIONS: In the
      present study Gleason 7 patients with primary grade 4 tumors and less than 50% of
      biopsy cores positive had an excellent prognosis after radical prostatectomy. Our
      data suggest that among Gleason 7 patients, the percentage of positive biopsies
      is a stronger predictor of biochemical progression-free survival than primary
      Gleason grade.

PMID- 16286114
TI  - Chromogranin A expression in familial versus sporadic prostate cancer.
AB  - OBJECTIVES: To evaluate whether a significant difference in chromogranin A (CgA)
      levels exist between patients with familial and sporadic cancer. METHODS: The
      study included 146 patients with clinically localized prostate adenocarcinoma
      (Stage T2N0M0), who underwent radical prostatectomy between June 1999 and June
      2004. Patients were considered to have a positive family history for prostate
      cancer when the index patient confirmed the diagnosis of prostate cancer in a
      first-degree relative (brother or father). On the day of surgery, a blood sample
      for the determination of serum prostate-specific antigen and CgA levels
      (radioimmunoassay) was obtained from all patients. In a subgroup of 20 patients,
      CgA mRNA expression was also evaluated by reverse transcriptase-polymerase chain
      reaction at the prostatic tissue level. RESULTS: A positive familial history was
      found in 28 (19.2%) of the 146 patients. The mean patient age in the familial
      group was significantly (P < 0.0001) lower than that in the sporadic group. No
      significant difference between the familial and sporadic groups was found in
      terms of prostate-specific antigen level (P = 0.9625) or Gleason score
      distribution (P = 0.4891). The familial group had significantly (P = 0.0013)
      lower serum CgA levels (43.3 +/- 12.7 ng/mL, median 39.9) compared with the
      sporadic group (55.9 +/- 19.4 ng/mL, median 54.1). The familial group also had
      significantly (P = 0.0432) lower expression of tissue CgA mRNA compared with the
      sporadic group. CONCLUSIONS: The result of significantly lower CgA expression in
      familial compared with sporadic prostate cancer cases suggests that
      neuroendocrine activity is not increased in familial cases and also confirms that
      familial cancer is not a more aggressive disease.

PMID- 16286116
TI  - Pretreatment predictors of posttreatment PSA doubling times for patients
      undergoing three-dimensional conformal radiotherapy for clinically localized
      prostate cancer.
AB  - OBJECTIVES: To determine whether pretreatment risk groups also predict for
      posttreatment prostate-specific antigen (PSA) doubling times (PSADTs).
      Pretreatment risk groups predict for posttreatment biochemical failure (BF) after
      conformal radiotherapy in patients with prostate cancer and posttreatment PSADTs
      can predict for prostate cancer-related deaths. METHODS: The study cohort
      consisted of 416 patients with clinically localized prostate cancer treated with
      conformal radiotherapy between 1989 and 2001. The patients were divided into low,
      intermediate, and high-risk groups. BF was defined using the American Society for
      Therapeutic Radiology and Oncology consensus definition. Patients with BF were
      grouped according to their PSADT (3 months or less, longer than 3 months to less
      than 6 months, 6 months to less than 12 months, and 12 months or longer). A
      Mantle-Haenszel chi-square metric tested for an association between the
      pretreatment risk group and the PSADT. Logistic regression multivariate analysis
      was performed to evaluate whether the pretreatment risk group predicted the
      PSADT. RESULTS: Of the 416 patients, 96 (23%), 194 (47%), and 126 (30%) were
      categorized as low, intermediate, and high risk, respectively. A total of 92
      patients (22%) experienced BF. Of these 92 patients, the PSADT was 3 months or
      less in 6 (7%), longer than 3 months to less than 6 months in 13 (14%), 6 months
      to less than 12 months in 35 (36%), and 12 months or longer in 38 (41%). The
      pretreatment risk group correlated significantly with the PSADT (P = 0.026).
      Logistic regression analysis revealed that intermediate and high-risk disease was
      significantly associated with shorter PSADTs (P = 0.039). CONCLUSIONS: A
      significant association between the pretreatment risk group and posttreatment
      PSADT was demonstrated. Use of this selection criterion at diagnosis for more
      aggressive treatment appears warranted.

PMID- 16286117
TI  - Maximal tumor diameter and the risk of PSA failure in men with specimen-confined
      prostate cancer.
AB  - OBJECTIVES: To evaluate whether the maximal tumor diameter (MTD) is significantly
      associated with the time to postoperative prostate-specific antigen (PSA)
      failure. METHODS: Between 1986 and 2002, 781 men with clinical Stage T1c-T2
      prostate cancer underwent radical prostatectomy. The MTD was recorded as the
      maximal dimension of the largest single focus of cancer from all 3-mm step
      sections. The median follow-up was 5.4 years (range 0.1 to 14.9); 242 men (31%)
      experienced PSA failure. A Cox regression analysis was used to determine the
      predictors of time to postoperative PSA failure. Kaplan-Meier estimates of PSA
      failure-free survival were made, dichotomized about the median MTD value, and
      compared using a two-sided log-rank test. RESULTS: The value of the MTD was
      significantly associated with the time to PSA failure (adjusted hazard ratio
      1.04, 95% confidence interval 1.01 to 1.07, P = 0.004), controlling for
      preoperative PSA level (P < 0.0001), prostatectomy Gleason score (P < 0.0001),
      and T stage (P < 0.0001). When margin status was added (P = 0.0004), the MTD
      approached statistical significance (P = 0.07). For patients with a preoperative
      PSA level of less than 10 ng/mL, prostatectomy Gleason score of 3 + 4 = 7 or
      less, Stage pT2-T3a, and negative margins, the value of the MTD significantly (P
      = 0.05) stratified the time to PSA failure, when dichotomized about the median
      value (13 mm), with 7-year PSA failure estimates of 17% versus 8%. CONCLUSIONS:
      Whether patients with traditionally low-risk but large MTD prostate cancer fare
      better when treated with adjuvant radiotherapy compared with salvage radiotherapy
      remains to be answered in the setting of a randomized trial.

PMID- 16286119
TI  - Systematic detection and repair of subclinical inguinal hernias at radical
      retropubic prostatectomy.
AB  - OBJECTIVES: Inguinal hernias occur in 15% of men within 1 to 2 years after
      radical retropubic prostatectomy (RRP). This suggests that many of these hernias
      may have been present at surgery, but not diagnosed. Beginning in September 2001,
      all patients undergoing RRP were carefully examined intraoperatively for the
      presence of a hernia or a dilated internal inguinal ring. In this study we define
      the frequency of inguinal hernias detected at RRP and the durability of repair.
      METHODS: Between September 2001 and December 2004, 430 patients underwent RRP by
      one surgeon. Hernias, detected in 142 men (33%), were repaired preperitoneally:
      direct hernias were repaired with mesh and indirect hernias with 2-0 Prolene
      suture. The patients were followed up for an average of 19 months (range 9 to
      36). Information on postoperative hernia status was available for 315 men
      (73.3%). RESULTS: Of the 430 patients, 142 (33%) had hernias repaired at RRP. Of
      these hernias, 32% were right sided, 28% left sided, and 40% bilateral; 34% were
      direct hernias and 66% indirect. Of the 142 patients who underwent intraoperative
      hernia repair, 95 (67%) had follow-up data, and 5 (5.3%) of that group developed
      a hernia postoperatively. None of the hernias repaired at RRP recurred. Recurrent
      hernias on the side of the repair occurred in 3.1%. CONCLUSIONS: Incidental
      inguinal hernias were commonly found (33%) at RRP. Two thirds of the defects
      detected were indirect. Clinical recurrence after repair was rare.

PMID- 16286118
TI  - Detection rates and biologic significance of prostate cancer with PSA less than
      4.0 ng/mL: observation and clinical implications from Tyrol screening project.
AB  - OBJECTIVES: To investigate the prostate cancer (PCa) detection rates and Gleason
      scores in patients with serum prostate-specific antigen (PSA) levels of 2.0 to
      3.9 ng/mL and 4.0 to 10 ng/mL (free PSA 18% or less), in a population-based
      screening project. With the use of prostate-specific antigen (PSA) screening,
      more PCa is being diagnosed at PSA values of less than 4 ng/mL. METHODS: A total
      of 3446 consecutive screening volunteers with a PSA level of 2.0 to 10.0 ng/mL
      (free PSA 18% or less) were assessed. Ten systematic prostate biopsies and an
      additional five Doppler-enhanced targeted biopsies were performed on the basis of
      age-specific PSA reference ranges. The cumulative frequency of detection and the
      Gleason scores were analyzed. RESULTS: The PCa detection rate for patients with a
      PSA value of 2.0 to 3.9 ng/mL (n = 1522, group 1) and 4.0 to 10.0 ng/mL (n =
      1924, group 2) was 21% (n = 320) and 30% (n = 572), respectively. Of the PCa
      cases detected, 37% were in men with a PSA level of 2 to 4 ng/mL. Statistically
      significant differences were found in age and prostate volume between groups 1
      and 2, with patients in the lower PSA group younger and having a smaller mean
      prostate volume (P = 0.0001). Of 313 patients with PCa and a PSA value of 2 to
      3.9 ng/mL, 24% had a Gleason score of 7 or greater compared with 33% of 560
      patients with a PSA value of 4.0 to 10.0 ng/mL (P = 0.004). CONCLUSIONS: Our data
      suggest that in a screening population, more than one third of PCa cases in men
      with a PSA level of 2 to 10 ng/mL will occur in those with a PSA value of 2 to
      3.9 ng/mL. Also, PCa cases with a low PSA level occur in younger patients and at
      lower stages with a smaller prostate volume.

PMID- 16286120
TI  - Estimation of treatment benefits when PSA screening for prostate cancer is
      discontinued at different ages.
AB  - OBJECTIVES: To estimate the declining benefits of screening for prostate cancer
      as patient age at screening increases. The benefits of prostate cancer screening
      decline with age because of the long natural history of prostate cancer and
      competing causes of death among older men. METHODS: We used a previously
      described Monte Carlo simulation based on a Markov model of prostate cancer
      detection in men aged 40 to 90 years and simulated prostate cancer screening in
      1000 populations of 1,000,000 men each. The age at the final prostate-specific
      antigen test in the model was varied to simulate the discontinuation of screening
      from age 50 to 80 years. The model outputs were the number of men treated, the
      number of prostate cancer deaths prevented by treatment, and person-years of life
      saved. RESULTS: The relationship between treatments required to prevent a death
      was not constant but widened with age. Compared with screening to age 65 years,
      screening to age 75 and 80 years required twice and three times, respectively,
      the number of treatments per person-year of life saved. CONCLUSIONS: Our results
      have helped to quantify the declining treatment benefit as the patient age at
      screening and treatment for prostate cancer increases. We believe that men older
      than 70 years should be carefully counseled about the declining benefits of
      prostate cancer detection with screening.

PMID- 16286121
TI  - Predictors of prostate cancer after initial diagnosis of atypical small acinar
      proliferation at 10 to 12 core biopsies.
AB  - OBJECTIVES: To evaluate the factors that predict prostate cancer detection by
      means of 10 to 12 core repeat biopsies in patients with atypical small acinar
      proliferation (ASAP) results on initial biopsy. METHODS: From 1998 to 2004, 110
      of 127 patients (87%) with a diagnosis of ASAP were rebiopsied with the same
      technique plus additional biopsies on the ASAP site (12.6 +/- 1.1 cores [mean +/-
      standard deviation]). Each histologic slide was reviewed blindly by a single
      experienced pathologist, who also differentiated highly suspicious (ASAPH) and
      not highly suspicious (ASAPB) lesions for cancer. RESULTS: On initial biopsy, a
      concomitant high-grade prostatic intraepithelial neoplasia (HGPIN) was present in
      26 patients (23%) with ASAP. The overall cancer detection rate was significantly
      higher in patients who had ASAP associated with HGPIN (58%), compared with
      patients who had isolated ASAP (35%; P = 0.04). The cancer detection rate was not
      significantly higher in patients with ASAPH than in those with ASAPB (49% versus
      33%, respectively; P = 0.11). In the group of patients who had isolated ASAP, the
      rate of cancer detection was significantly higher in patients who had a prostatic
      volume less than 50 mL (56%) than in patients with a prostatic volume of 50 mL or
      more (27%; P = 0.03). CONCLUSIONS: The cancer detection rate was significantly
      higher in patients with an ASAP associated with HGPIN on initial biopsy than in
      patients with isolated ASAP. In ASAP patients, the detection rate was lower for
      patients with a larger prostate than in those with a smaller prostate.

PMID- 16286122
TI  - Prognostic significance of perineural invasion on biochemical progression-free
      survival after prostate brachytherapy.
AB  - OBJECTIVES: To evaluate the influence of perineural invasion (PNI) in the biopsy
      specimen on biochemical progression-free survival in hormone-naive patients with
      prostate cancer undergoing brachytherapy. METHODS: A total of 512 consecutive
      hormone-naive patients (173 low risk, 212 intermediate risk, and 127 high risk)
      underwent brachytherapy for clinical Stage T1b-T2cNxM0 (2002 American Joint
      Committee on Cancer staging system) prostate cancer. No patient underwent seminal
      vesicle or pathologic lymph node staging. All patients had undergone
      brachytherapy at least 3 years before analysis. The median follow-up was 5.3
      years. Biochemical progression-free survival was defined by a prostate-specific
      antigen (PSA) cutpoint of 0.4 ng/mL or less after nadir and by the American
      Society for Therapeutic Radiology and Oncology consensus definition. PNI was
      defined as carcinoma tracking along, or around, a nerve within the perineural
      space. RESULTS: PNI was documented in 133 patients (26.0%). For both biochemical
      progression-free definitions, 94.0% and 94.9% of patients with and without PNI,
      respectively, remained free of biochemical progression. The median time to
      failure in patients with and without PNI was 17.2 and 17.9 months, respectively.
      For the biochemically disease-free cohort, the median posttreatment PSA level was
      less than 0.1 ng/mL. On univariate Cox regression analysis, the pretreatment PSA
      level, percentage of positive biopsies, prostate volume, and Gleason score
      predicted for biochemical outcome. PNI did not approach statistical significance
      (P = 0.671). On multivariate analysis, only pretreatment PSA (P < 0.001) and the
      percentage of positive biopsies (P < 0.001) maintained statistical significance.
      CONCLUSIONS: In hormone-naive brachytherapy patients implanted with generous
      periprostatic treatment margins, the presence of PNI in the biopsy specimen did
      not adversely affect 8-year biochemical progression-free survival.

PMID- 16286123
TI  - Open-label trial evaluating the safety and efficacy of zoledronic acid in
      preventing bone loss in patients with hormone-sensitive prostate cancer and bone
      metastases.
AB  - OBJECTIVES: To evaluate the efficacy and safety of zoledronic acid in preventing
      bone loss in patients with hormone-sensitive prostate cancer and bone metastases
      who were receiving androgen deprivation therapy. METHODS: Patients received
      zoledronic acid 4 mg as a 15-minute infusion every 3 weeks for 1 year. Bone
      mineral density of the lumbar spine (L2 to L4) and total hip was measured by dual
      energy x-ray absorptiometry at baseline and 12 months. Biochemical markers of
      bone turnover (N-telopeptide and bone alkaline phosphatase) and serum creatinine
      levels were evaluated at baseline and during the study. Skeletal-related events
      were assessed at each study visit. RESULTS: Of the 221 enrolled patients, 202 and
      221 patients were included in the efficacy and safety analyses, respectively. The
      mean increase in bone mineral density of the lumbar spine and total hip was 7.7%
      (P <0.001) and 3.6% (P <0.001), respectively. Decreases in N-telopeptide and bone
      alkaline phosphatase levels were significant and sustained. The median time to
      the first skeletal-related event was not reached; 11.9% of patients had a
      skeletal-related event. Arthralgia (20.4%), nausea (14%), fatigue (14%), and back
      pain (12.2%) were the most common adverse events. Adverse events due to renal
      function deterioration were infrequent. The mean maximal change in serum
      creatinine level from baseline was 0.3 mg/dL. CONCLUSIONS: Zoledronic acid
      administration for 1 year to patients with hormone-sensitive prostate cancer and
      bone metastases who were receiving androgen deprivation therapy was safe and
      prevented bone loss, as demonstrated by significant increases in bone mineral
      density and sustained suppression of biochemical markers of bone turnover.

PMID- 16286124
TI  - Impact of obesity on prostate cancer recurrence after radical prostatectomy: data
      from CaPSURE.
AB  - OBJECTIVES: To determine the association between obesity and prostate cancer
      recurrence after primary treatment with radical prostatectomy. METHODS: Data were
      abstracted from CaPSURE, a disease registry of 10,018 men with prostate cancer.
      We included 2131 men who had undergone radical prostatectomy between 1989 and
      2003 and had body mass index (BMI) information available. Recurrence was defined
      as two consecutive prostate-specific antigen (PSA) levels of 0.2 ng/mL or greater
      or any second treatment. Patients were risk stratified using the PSA level,
      Gleason grade, and clinical T stage. RESULTS: Patients were followed up for a
      median of 23 months. Of the 2131 patients, 251 (12%) developed recurrence at a
      median of 13 months (range 1 to 107); 183 (9%) of these men had PSA failure and
      68 (3%) received a second treatment. After adjusting for risk group, ethnicity,
      age, and comorbidities, a significant association was found between an increasing
      BMI and disease recurrence (P = 0.028). Very obese patients (BMI 35 kg/m2 or
      more) were 1.69 times more likely to have recurrence relative to men of normal
      weight (BMI less than 25.0 kg/m2; 95% confidence interval [CI] 1.01 to 2.84). An
      increasing PSA level (P <0.0001) and Gleason grade (P <0.0001) were also
      associated with recurrence. Ethnicity was not significantly associated with
      either BMI or PSA recurrence (P = 0.685 and P = 0.068, respectively).
      CONCLUSIONS: The results of our study have shown that obesity is an independent
      predictor of prostate cancer recurrence. Because of the increased comorbidities
      and greater rates of recurrence, obese individuals undergoing radical
      prostatectomy need vigilant follow-up care.

PMID- 16286125
TI  - A pilot study of lymphotrophic nanoparticle-enhanced magnetic resonance imaging
      technique in early stage testicular cancer: a new method for noninvasive lymph
      node evaluation.
AB  - OBJECTIVES: To evaluate whether lymphotrophic nanoparticle-enhanced magnetic
      resonance imaging (LNMRI) can be used as a method for detecting metastatic
      disease within retroperitoneal nodes in patients with testicular cancer. METHODS:
      Stage I testicular cancer patients were prospectively enrolled and underwent a
      pelvic MRI both before and 24 hours after intravenous ferumoxtran-10
      administration. Nodal sampling was performed by computed tomography-guided biopsy
      or laproscopic surgery and reviewed by a pathologist without knowledge of the
      LNMRI results. RESULTS: In 18 patients, 42 nodes were sampled, of which 25 were
      benign and 17 were malignant. The sensitivity of LNMRI for malignant lymph node
      involvement was 88.2%, specificity was 92%, and the accuracy was 90.4%. On the
      other hand, the sensitivity of size criteria for detecting malignant nodes was
      70.5%, the specificity was 68%, and the accuracy was 69%. CONCLUSIONS:
      Lymphotrophic nanoparticle-enhanced MRI is safe and accurate for detecting nodal
      metastases in patients with testicular cancer. Lymphotrophic nanoparticle
      enhanced MRI yields higher sensitivity and specificity when compared with
      unenhanced MRI or conventional CT scanning. Although our results are encouraging,
      the precise role of this tool in early stage testicular cancer remains to be
      determined.

PMID- 16286126
TI  - Microsurgical varicocelectomy for recurrent or persistent varicoceles associated
      with orchalgia.
AB  - OBJECTIVES: To assess the effectiveness of microsurgical varicocelectomy for the
      treatment of recurrent varicoceles associated with orchalgia. METHODS: Twelve
      patients with recurrent (or persistent) painful varicocele underwent
      microsurgical varicocelectomy. Follow-up assessment was available for 11 patients
      and included a postoperative questionnaire and scrotal examination. RESULTS: Pain
      disappeared completely in 6 of the 11 patients, and pain severity was reduced in
      4 additional patients after microsurgical varicocelectomy, for an overall
      favorable response in 10 of 11 patients. Most men returned to full activities
      within 1 month after microsurgical varicocelectomy. CONCLUSIONS: Microsurgical
      varicocelectomy is an effective testicular-sparing treatment modality for
      recurrent painful varicocele and should be offered to patients who have failed
      conservative measures.

PMID- 16286127
TI  - Inguinal versus subinguinal varicocele vein ligation using magnifying loupe under
      local anesthesia: which technique is preferable in clinical practice?
AB  - OBJECTIVES: To compare the intraoperative results of inguinal versus subinguinal
      varicocelectomy using magnifying loupe, in terms of vein ligation and arterial
      preservation, recurrence rate, and patient tolerability. METHODS: Ninety-nine
      patients were randomized to undergo a varicocele repair with an inguinal or a
      subinguinal approach under local anesthesia. Data concerning the number of veins
      ligated and arterial preservation were recorded during each procedure. The amount
      of intraoperative and postoperative pain was assessed by means of visual analogue
      scale (VAS) scores. The recurrence rate was documented by color Doppler
      ultrasound examination. RESULTS: The average number of ligated veins was 5.6 with
      a subinguinal dissection and 4.4 with the inguinal approach. Inadvertent injury
      of the spermatic artery occurred in 6 of 47 subinguinal and 3 of 50 inguinal
      dissections; the artery could not be identified during 2 subinguinal and 1
      inguinal dissection. Recurrent varicocele was detected in 8% and 14.9% of
      patients after an inguinal and a subinguinal approach, respectively. The
      intraoperative VAS score was significantly higher in the inguinal than in the
      subinguinal patients (P = 0.008). CONCLUSIONS: In our hands, the inguinal
      approach to the spermatic cord showed a trend toward an easier preservation of
      the artery and a reduced incidence of persistent pathologic vein reflux. The
      subinguinal approach had a lower degree of intraoperative pain. On the whole, an
      inguinal repair might be preferable when magnifying loupe are used for
      varicocelectomy.

PMID- 16286128
TI  - Acetyl-L-carnitine plus propionyl-L-carnitine improve efficacy of sildenafil in
      treatment of erectile dysfunction after bilateral nerve-sparing radical
      retropubic prostatectomy.
AB  - OBJECTIVES: To determine whether propionyl-L-carnitine (PLC) plus acetyl-L
      carnitine (ALC) improves the effectiveness of sildenafil in restoring sexual
      potency after bilateral nerve-sparing radical retropubic prostatectomy. METHODS:
      We analyzed the data from 96 patients who had undergone bilateral nerve-sparing
      radical retropubic prostatectomy: 33 were given placebo (group 1), 32 used PLC 2
      g/day plus ALC 2 g/day plus sildenafil 100 mg when needed (group 2), and 35 used
      sildenafil alone (group 3). The studied variables were sexual function (assessed
      through sexual behavior interviews and the International Index of Erectile
      Function), peak systolic velocity and end-diastolic velocity of cavernosal
      arteries (assayed by dynamic echo-color Doppler), the percentage of patients able
      to achieve a positive intracavernous injection test, and side effects. RESULTS:
      Placebo proved ineffective and sildenafil and sildenafil plus ALC and PLC proved
      effective. The International Index of Erectile Function-15 scores of the group 2
      patients were significantly greater than those of group 3 in the following
      domains: erectile function, sexual intercourse satisfaction, orgasm, and general
      sexual well-being. The drugs did not significantly modify the score in the sexual
      desire domain or in the peak systolic velocity or end-diastolic velocity of the
      cavernosal arteries. Sexual behavior interviews revealed that 2 of 29 in group 1,
      28 of 32 in group 2, and 20 of 39 in group 3 attained satisfactory sexual
      intercourse (P <0.01). Only group 2 had a significantly increased percentage of
      patients with a positive intracavernous injection test after therapy (36.4%
      versus 63.6%; P <0.01). ALC plus PLC did not significantly improve the side
      effects of sildenafil. CONCLUSIONS: PLC and ALC proved to be safe and reliable in
      improving the efficacy of sildenafil in restoring sexual potency after bilateral
      nerve-sparing radical retropubic prostatectomy.

PMID- 16286129
TI  - Patient-reported sexual function after oral mucosa graft urethroplasty for
      hypospadias.
AB  - OBJECTIVES: To evaluate sexual function after oral mucosa graft urethroplasty
      (OMGU) for hypospadias. Few long-term patient-reported data are available
      regarding sexual function after surgery for hypospadias. METHODS: We identified
      patients aged 18 years or older at the time of this survey who had undergone OMGU
      for hypospadias between 1992 and 2003. We evaluated sexual function and
      satisfaction using the 15-item International Index of Erectile Function (IIEF
      15). RESULTS: Of the 16 adult patients, we located 14, of whom 11 (79%)
      participated. Previous hypospadias repair had failed in all 11 before OMGU. The
      median age at OMGU was 17.5 years. The median follow-up time was 4.7 years. Of
      the 10 sexually active patients, the mean score on the IIEF-15 was 64.6 +/- 11.9
      (maximal possible score 75). Erectile function was excellent, with all 10 able to
      achieve an erection most or all of the time (mean erection domain score 26.8 +/-
      6.1). All 10 experienced sensation of orgasm most or all the time, although 1
      never ejaculated and 2 ejaculated rarely (mean orgasm domain score 8.9 +/- 1.8).
      All 10 reported that they were moderately (n = 6) or very (n = 4) satisfied with
      their overall sex life (mean satisfaction domain score 8.3 +/- 1.9). Neither
      occurrence of post-OMGU complications nor satisfaction with penile appearance was
      significantly associated with the IIEF-15 scores or overall sexual satisfaction.
      CONCLUSIONS: Long-term sexual function and satisfaction was excellent in these
      patients after OMGU for hypospadias. Adolescent boys and men with failed
      hypospadias repairs, as well as parents of boys with hypospadias, can be
      counseled that most patients who undergo OMGU are likely to have satisfactory
      sexual function as adults.

PMID- 16286134
TI  - Double dartos flaps in tubularized incised plate hypospadias repair.
AB  - OBJECTIVES: To compare the single dartos flap with double dartos flap coverage.
      Two overlapping layers of dartos flap were fashioned and fixed in front of the
      neourethra after tubularized incised plate hypospadias repair to prevent
      urethrocutaneous fistula and glanular torsion. METHODS: A total of 96 boys with
      distal hypospadias were treated with tubularized incised plate urethroplasty.
      They were divided into two groups. Group 1 (54 patients) had a single dartos flap
      covering. Group 2 (42 patients) had double dartos flap coverings. The dissected
      dorsal dartos flap was bisected vertically to form two pedicled wings. Each wing
      was rotated laterally from either side of the glans to cover the neourethra
      ventrally in a double-layer fashion. RESULTS: In group 1, 2 patients (3.7%)
      developed fistula, 49 (90.7%) had mild glanular torsion, and 5 (9.3%) had
      moderate glanular torsion. None of group 2 developed fistula or glanular torsion
      postoperatively. CONCLUSIONS: Double dartos flaps covering of the neourethra is a
      simple procedure that was superior to single flap covering for the prevention of
      urethrocutaneous fistula after tubularized incised plate urethroplasty. Glanular
      torsion did not occur when double dartos flaps were used.

PMID- 16286132
TI  - Voiding dysfunction: outcome in infants with congenital vesicoureteral reflux.
AB  - OBJECTIVES: To assess the rate of development of voiding dysfunction as an
      outcome in patients with congenital vesicoureteral reflux. METHODS: A
      computerized database was used to review the medical records of all patients with
      congenital reflux diagnosed before 6 months of age from 1988 to 2002. Only those
      infants with reflux who were followed up for at least 6 months past the age of
      toilet training were included. The parameters tabulated in this group included
      the presence of frequency, daytime wetting, urge incontinence, and infrequent
      voiding. The variables were summarized using contingency tables, and associations
      were evaluated using chi-square analysis and Fisher's exact test. RESULTS: Of 342
      patients (145 boys and 197 girls) with reflux, 67 (19.6%) developed voiding
      dysfunction (17.9% boys and 20.8% girls). No statistically significant difference
      was found between high grade (IV and V) and low grade (I and II) or grade III
      reflux, or between unilateral and bilateral reflux for the development of voiding
      dysfunction. Of the patients with reflux who had renal damage on
      dimercaptosuccinic acid scan, 24.3% of girls and 30.4% of boys developed voiding
      dysfunction, which was not significantly different from those without renal
      damage. CONCLUSIONS: Approximately 20% of patients with vesicoureteral reflux
      diagnosed before 6 months of age demonstrated dysfunctional voiding after the age
      of toilet training. Voiding dysfunction occurred independent of sex, laterality,
      or severity of vesicoureteral reflux. Infants with renal damage on
      dimercaptosuccinic acid scan developed dysfunctional voiding only at a slightly
      greater, but not significantly different, rate than those with normal kidneys.

PMID- 16286135
TI  - Novel device to assist urethrovesical anastomosis during laparoscopic radical
      prostatectomy.
AB  - We evaluated a novel urethral sound (Benique sound-Karl Storz) to assist suturing
      during laparoscopic radical prostatectomy. This sound provides for a more secure
      grip compared with the traditional sound, thereby affording controlled traction
      of the gland during the procedure and smooth coordinated movements of the sound
      during the anastomosis.

PMID- 16286136
TI  - Transdiaphragmatic-intrapericardiac approach to supradiaphragmatic vena cava
      invasion secondary to renal cell carcinoma: a novel surgical approach.
AB  - INTRODUCTION: A combined abdominal and thoracic surgical approach is the
      treatment of choice for renal cell carcinoma with secondary thrombus extending to
      the supradiaphragmatic vena cava and initially into the right atrium. This
      procedure usually requires a median sternotomy with cardiopulmonary bypass and
      deep hypothermic circulation arrest or, alternatively, venovenous bypass. In this
      report, we present a transdiaphragmatic-intrapericardiac approach to
      supradiaphragmatic thrombus extending to the atrium that avoids the
      disadvantages, mortality, and morbidity related to cardiopulmonary bypass and
      deep hypothermic circulatory arrest or venovenous bypass. TECHNIQUE: We describe
      a combined abdominal and transdiaphragmatic-intrapericardiac approach that was
      performed in 3 patients with renal cell carcinoma with secondary thrombus
      extending to the atrium. The estimated blood loss of the patients ranged from 1.1
      to 2.8 L (mean 1.5). The total operative time ranged from 3 hours, 20 minutes to
      4 hours. No postoperative complications were observed in any patient.
      CONCLUSIONS: This technique allows excellent exposure of the supradiaphragmatic
      inferior vena cava through a 10-cm incision and optimal control of the distal
      thrombus edge when it reaches the right atrium. This approach is safer, faster,
      easier, and minimally invasive and avoids cardiopulmonary bypass with deep
      hypothermic cardiac arrest or venovenous bypass.

PMID- 16286137
TI  - Images in clinical urology. A case of urethral rhinosporidiosis.

PMID- 16286138
TI  - Images in clinical urology. Late complication after penile elongation.

PMID- 16286139
TI  - Interdigitating dendritic cell sarcoma of urinary bladder mimicking large
      intravesical calculus.
AB  - Interdigitating dendritic cell sarcomas are extremely rare neoplasms with an
      unpredictable clinical course that usually occur in lymph nodes. We report the
      first adult patient with interdigitating dendritic cell sarcoma involving the
      bladder. A 71-year-old man presented with lower urinary tract symptoms and gross
      hematuria. Cystoscopy and transabdominal ultrasonography showed a large
      hyperechoic intravesical mass. The histologic analysis revealed a spindled cell
      neoplasm with an immunophenotype consistent with interdigitating dendritic cell
      sarcoma. Complete resection was achieved, and the patient was well without
      evidence of tumor 6 years after surgery. Urologists should be aware of this
      entity, which should be included in the differential diagnosis of bladder tumors.

PMID- 16286140
TI  - Lymphoepithelioma-like carcinoma of the ureter.
AB  - Lymphoepithelioma-like carcinoma is an undifferentiated epithelial tumor with a
      prominent lymphocytic infiltrate and is rarely seen in the upper urinary tract.
      Only 3 and 2 cases involving the ureter and renal pelvis, respectively, have been
      reported. We report the fourth documented case of lymphoepithelioma-like
      carcinoma of the ureter. Tumor cells were immunoreactive to cytokeratin and
      negative for Epstein-Barr virus. Our patient was disease free 30 months after
      nephroureterectomy. The prognosis is favorable for pure lymphoepithelioma-like
      carcinoma of the upper urinary tract.

PMID- 16286141
TI  - Renal artery pseudoaneurysm after laparoscopic partial nephrectomy.
AB  - Delayed bleeding from a renal artery pseudoaneurysm is a rare occurrence after
      partial nephrectomy. We present 2 cases of renal artery pseudoaneurysm after
      laparoscopic partial nephrectomy. One patient presented with gross hematuria and
      flank pain and the other presented with flank pain and a decreasing hematocrit.
      The patients were treated with selective angioembolization of the pseudoaneurysm.
      The etiology and management of this potentially life-threatening condition are
      discussed.

PMID- 16286142
TI  - Erosion of magnets into the scrotum in the pediatric patient.
AB  - A 12-year-old boy presented to the emergency department complaining that he had
      "magnets stuck in [his] scrotum." Examination revealed a wedge of scrotal skin
      with a pit on each side without visible objects. A radiograph confirmed
      intrascrotal foreign bodies. Surgical exploration was required to remove the
      magnets. This is, to our knowledge, the first reported case of a foreign body in
      a child leading to pressure necrosis and erosion into the genital tract.

PMID- 16286143
TI  - Use of buccal mucosa to simulate the coronal sulcus after traumatic penile
      amputation.
AB  - Traumatic penile amputation is a rare but catastrophic complication of newborn
      circumcision, usually involving a portion of, or the entire, glans penis.
      Emergent reimplantation is necessary to prevent glans loss. However, loss of the
      coronal sulcus might occur despite successful reimplantation, resulting in a
      cosmetically unacceptable appearance. We report such a case involving a newborn
      who suffered partial penile glans amputation and loss of the coronal sulcus after
      reimplantation, successfully treated with buccal mucosa grafting.

PMID- 16286145
TI  - Port site metastases after robot-assisted laparoscopic radical cystectomy.
AB  - Laparoscopy has become a well-established alternative to open surgery for the
      management of many urologic tumors. Metastases at one of the port sites is not a
      common complication, though there are some reports of port site metastases after
      laparoscopic management for renal tumors and pelvicaliceal tumors, as well as
      after laparoscopic lymphadenectomy. Herein, we report a case of port site
      metastases after robot-assisted laparoscopic radical cystectomy for muscle
      invasive bladder cancer. To the best of our knowledge this is the first case of
      such pathology to be reported. Although rare, the laparoscopic surgeon should be
      aware of such complications when dealing with malignant masses.

PMID- 16286144
TI  - Artificial ureters in renal transplantation.
AB  - Ureteral strictures in transplanted renal units are initially managed by balloon
      dilation and indwelling stents. When endourologic management fails,
      ureteroneocystostomy or pyeloureteral anastomosis to the native ureter is the
      treatment of choice. Nevertheless, such procedures are not always successful. We
      present what we believe to be the first two North American cases of silicone
      polyester artificial ureters (pyelovesical bypass graft) after failed
      endourologic or open management of ureteral strictures after renal
      transplantation. After 12 and 15 months of follow-up, the renal function was
      stable, with no evidence of obstruction. Long-term follow-up is needed to monitor
      the rate of late encrustation and obstruction.

PMID- 16286146
TI  - Rare cause of ureteral obstruction.
AB  - This report presents bilateral ureteral obstruction due to possible ureteritis in
      a bone marrow transplant patient with resurgence of BK virus after hemorrhagic
      cystitis. This is believed to be the first description of this type of ureteral
      obstruction. The presented case includes the management plan.

PMID- 16286147
TI  - Intravesical hydatid cyst.
AB  - A case of intravesical hydatid cyst is reported. The cyst was completely
      evacuated cystoscopically with intravesical instillation of a scolicidal agent
      (hydrogen peroxide) to destroy scolices and daughter cysts. The postoperative
      course was uneventful, and follow-up did not show evidence of recurrence. Because
      this is the first case, to our knowledge, to be reported, little is known about
      the nonoperative management of such hydatid localization. A recommendation is
      made, however, to adopt this minimally invasive procedure.

PMID- 16286148
TI  - Abnormal fluorescence in situ hybridization analysis in collecting duct
      carcinoma.
AB  - Renal collecting duct carcinoma is a rare form of renal cancer known to present
      in a variety of ways that are often similar to presentations of renal cell
      carcinoma or transitional cell carcinoma. Little information is available
      concerning the use of cytology and fluorescence in situ hybridization (FISH) in
      the diagnosis of collecting duct carcinoma. The available literature contains
      cases with atypical cytology, but no collecting duct carcinoma cases with
      abnormal FISH results have been reported. We report a case of renal collecting
      duct carcinoma presenting with atypical cytology and abnormal FISH results.

PMID- 16286149
TI  - Defining maximal renal tolerance to warm ischemia in porcine laparoscopic and
      open surgery model.
AB  - OBJECTIVES: To establish the upper limit for warm ischemia time (WIT) beyond
      which irreversible renal failure will occur in a single-kidney porcine model. The
      maximal renal tolerance during WIT is currently under revision. Traditionally, 30
      minutes was defined as the safe limit for renal WIT. However, accumulating data
      have suggested that a WIT of up to 90 minutes may not result in permanent damage.
      METHODS: Twenty female pigs weighing 60 to 80 lb at arrival underwent initial
      right laparoscopic nephrectomy to create a single-kidney model. Twelve days
      later, the animals were randomized into four groups of 5 animals each: 120
      minutes of open WIT, 120 minutes of laparoscopic WIT, 5 open controls, and 5
      laparoscopic controls. Renal function was assessed with serial glomerular
      filtration rate and serum creatinine measurements, which were assessed
      preoperatively and on postoperative days (PODs) 1, 3, 8, and 15. RESULTS: No
      significant difference existed between the laparoscopic and open groups. The
      glomerular filtration rate reached the lowest value and the serum creatinine
      levels peaked on POD 3 and were significantly different from baseline at PODs 1,
      3, 8, and 15. Renal function did not return to baseline by POD 15, and 66% of the
      animals showed significant renal insufficiency (more than 25% decline in
      glomerular filtration rate) in the study group. CONCLUSIONS: After 120 minutes of
      WIT, no difference in renal function recovery was observed between the
      laparoscopic and open techniques. A WIT of 120 minutes produced significant renal
      failure and mortality. Thus, 120 minutes of WIT in the single kidney porcine
      model exceeds the kidney's tolerance to ischemia.

PMID- 16286150
TI  - Herpes simplex virus type 1 mutant HF10 oncolytic viral therapy for bladder
      cancer.
AB  - OBJECTIVES: To investigate the antitumor effects of the oncolytic herpes simplex
      virus (HSV) type 1 mutant HF10 on human and murine bladder cancer cells (T24 and
      MBT-2) in vitro and in immunocompetent mouse models. METHODS: In vitro viral
      oncolytic activity and the replication ability of HF10 were measured in T24 and
      MBT-2 cells. To evaluate the therapeutic efficacy of HF10, disseminated
      peritoneal and bladder cancer models using MBT-2 cells were established in
      C3H/HeJ mice. The therapeutic efficacy was estimated from the survival rates and
      histopathologic analyses. RESULTS: HF10 replicated well in both T24 and MBT-2
      cells, and it induced extensive cell lysis. Treatment with HF10 significantly
      prolonged the survival periods and increased the survival rates in both models
      tested. Immunohistochemical studies showed that HSV antigens were detected in the
      bladders 1 and 3 days after intravesical treatment with HF10 in nonimmunized
      mice, but only at 1 day after HF10 treatment in preimmunized, HSV-1 antibody
      positive mice. A large number of inflammatory cells infiltrated into the bladder
      mucosa at 3 days after HF10 treatment in the preimmunized mice. CONCLUSIONS:
      These results suggest that HF10, a novel oncolytic HSV-1 mutant, is a promising
      agent for the treatment of superficial bladder cancer.

PMID- 16286151
TI  - Usefulness of histologic homogeneity estimation of muscle-invasive urinary
      bladder cancer in an individual prognosis: a mapping study.
AB  - OBJECTIVES: To examine the histologic homogeneity of muscle-invasive urothelial
      cell carcinoma of the bladder, with conventional and nonconventional (eg,
      squamous, glandular, or variants) differentiation, to assess its influence on
      prognosis. METHODS: With organ mapping, we investigated 38 cystectomy specimens.
      Each entire bladder was cut into 88 slices according to an identical topographic
      scheme. From all the bladder slices, 1231 slices that included tumor were chosen
      for the histologic study. We examined the diagnostic significance, extension, and
      number of histologic differentiation types. RESULTS: The extension of
      nonconventional differentiation, with any proportion of histologic type, had an
      unfavorable impact on survival time. The number of nonconventional
      differentiation types increases in the presence of a sarcomatoid, an
      undifferentiated, a nested, or a micropapillary pattern. The increased number of
      differentiation types had an unfavorable influence on survival time. Patients
      with a more than 80% classic urothelial cell carcinoma pattern had a favorable
      prognosis, which increased further with increasing percentages of this
      differentiation type. CONCLUSIONS: Muscle-invasive urinary bladder cancers are
      not a homogenous group of tumors. Our results suggest that a precise assessment
      of the extension and number of histological differentiation types may be an
      individual prognostic factor. Conventional differentiation with at least 80%
      extension seems to be prognostically favorable. Nonconventional differentiation,
      especially with greater extension and a greater number of types, could imply a
      worse prognosis.

PMID- 16286152
TI  - Evaluation of two techniques of partial urethral obstruction in the male rat
      model of bladder outlet obstruction.
AB  - OBJECTIVES: To perform a comparison to determine which of two methods of partial
      urethral ligation produces the most consistent outcome and fewest side effects.
      Such a study has not been previously reported. Partial urethral ligation is a
      means of causing reproducible bladder outlet obstruction. In the male rat model,
      partial urethral obstruction can be performed either by perineal incision and
      bulbous urethral ligation or retropubic incision and midprostatic obstruction.
      METHODS: Fifteen male Sprague-Dawley rats were studied. Five were selected for
      bulbous urethral obstruction through a perineal incision, five for midprostatic
      obstruction using a retropubic approach, and five for a sham operation through a
      perineal incision. RESULTS: The operative time was shorter and morbidity lower
      with the perineal approach compared with the retropubic approach. Inflammation or
      infection, or both, were seen in the prostate, bladder, proximal urethra,
      ureters, and kidneys in the rats in which a midprostatic obstruction was
      performed. The proximal urethra and prostate were mildly inflamed in those rats
      that underwent bulbous obstruction. Sham-operated rats exhibited mild prostatitis
      only. CONCLUSIONS: The perineal approach to the bulbous urethra is the method of
      choice for creating a partial urethral obstruction model of bladder outlet
      obstruction in the male rat.

PMID- 16286153
TI  - Five-alpha-reductase expression in benign and malignant urothelium: correlation
      with disease characteristics and outcome.
AB  - OBJECTIVES: To evaluate 5-alpha-reductase (5alphaR) expression in benign and
      malignant urothelium and to assess the relationship between 5alphaR expression
      and tumor stage, tumor grade, and clinical outcome in patients with urothelial
      carcinoma/transitional cell carcinoma. METHODS: We performed immunohistochemistry
      for 5alphaR on 53 urothelial specimens from 36 patients with transitional cell
      carcinoma treated at our institution between June 2002 and July 2003. For each
      tumor and the adjacent nontumor urothelium, a semiquantitative staining score was
      calculated. We used t tests and analysis of variance to compare the staining
      score across groups. Kaplan-Meier and logistic regression analyses were performed
      to assess the relationship between 5alphaR expression and clinical outcome.
      RESULTS: 5alphaR was expressed throughout the non-neoplastic urothelium. Nontumor
      urothelium had greater mean staining scores than did tumor specimens (160.1
      versus 105.5, P <0.01). Low staining scores were associated with high grade (P
      <0.05), Stage pT3, pT4, and pTis (P <0.05), and disease progression (P <0.05). A
      staining score less than the median was a risk factor for progression (odds ratio
      6.2, P <0.01) on univariate regression analysis. Patients with a staining score
      less than the median had a greater likelihood of disease progression (log-rank P
      <0.05) and cause-specific mortality (log-rank P <0.05). CONCLUSIONS: We
      demonstrated 5alphaR expression in human urothelium and found that expression is
      decreased in transitional cell carcinoma in relation to tumor grade and stage.
      Decreased 5alphaR expression was associated with disease progression and cause
      specific mortality.

PMID- 16286155
TI  - Reliability of classification of erectile function domain of the international
      index of erectile function in patients affected by localized prostate cancer who
      are candidates for radical prostatectomy.

PMID- 16286156
TI  - Gemcitabine in intravesical treatment of Ta-T1 transitional cell carcinoma of the
      bladder.

PMID- 16286158
TI  - The Rb1 fraction of ginseng elicits a balanced Th1 and Th2 immune response.
AB  - Porcine parvovirus (PPV) vaccines containing different adjuvants were evaluated
      for inducing Th1 or Th2 type of immunity in mice. Isotypes of antigen specific
      antibodies and levels of cytokines in serum and in lymphocyte culture
      supernatants measured by ELISA and the Gyrolab Bioaffy were used to determine the
      polarisation of the immune response. Enumeration of cytokine secreting cells was
      carried out by ELISPOT assays. Vaccines containing the ginseng-fraction Rb1
      induced serum-detectable amounts of IL-4 and IL-10 as early as 24h after primary
      injection that was confirmed in sera collected at 24 and 72 h post re
      vaccination. Five weeks after booster, immune lymphocytes were still producing
      large amounts of cytokines including IFN-gamma, IL-2, IL-4, IL-10 and TNF-alpha
      and the antibody titres were still similar to those titres recorded 1 week post
      booster. The Rb1 adjuvanted vaccines stimulated similar titres of antigen
      specific IgG1, IgG(2a) and IgG(2b). Thus, the cytokine and the serological data
      indicated that the Rb1 fraction of ginseng elicits a balanced Th1 and Th2 immune
      response.

PMID- 16286159
TI  - Enteric vaccines for pediatric use. Workshop summary.
AB  - Diarrheal diseases remain a major cause of death in children under 5 in less
      developed countries (LDCs). Vaccine development and implementation offers the
      best near-term approach to alleviating this problem. For this reason, a workshop
      to examine the possibilities for making enteric vaccines available to meet the
      specific needs of children in LDCs was convened in Virginia on April 24-26, 2004.
      Discussants considered research and development needs, regulatory and business
      issues, and previous experiences with enteric vaccine development and
      implementation. No insurmountable roadblocks to progress in this area were noted,
      and the possibility currently exists that properly supported efforts will enable
      the realization of enteric vaccines for pediatric use.

PMID- 16286160
TI  - Vasopressin antagonism in heart failure.
AB  - Treatment of chronic heart failure (HF) is based on interference with the renin
      angiotensin-aldosterone system and the adrenergic nervous system. Diuretics are
      used in volume-expanded patients. Insights from clinical trials and registries
      establish the need to consider correcting both cardiac loading conditions and
      nonload-related biological factors if HF therapy is to be optimized. Arginine
      vasopressin (AVP) represents a potentially attractive target for therapy in both
      acute and chronic HF. Excessive AVP secretion could contribute to both systolic
      and diastolic wall stress via V1a- and V2-mediated effects on the peripheral
      vasculature and on water retention. Arginine vasopressin also may directly and
      adversely affect myocardial function due to the effect of V1a activation on
      myocardial contractility and cell growth. Last, AVP may contribute to
      hyponatremia, a powerful predictor of poor outcome in HF. The development of
      effective nonpeptide antagonists to both the V1a and V2 receptors for AVP now
      allows for testing the hypotheses that interfering with AVP-mediated signaling
      could be beneficial in HF. This review summarizes the theoretical rationale for
      further development of such therapy, reviews the status of current compounds
      under development, and suggests key issues that need to be addressed as these
      agents undergo further clinical testing.

PMID- 16286161
TI  - High-density lipoprotein function recent advances.
AB  - Although high-density lipoproteins (HDL) possess many features that contribute to
      the association between elevated HDL cholesterol and protection from
      atherosclerosis, these lipoproteins may be modified in certain individuals and/or
      circumstances to become proinflammatory. The ability of HDL to inhibit or
      paradoxically to enhance vascular inflammation, lipid oxidation, plaque growth,
      and thrombosis reflects changes in specific enzyme and protein components. The
      anti-inflammatory and proinflammatory functional properties of HDL can now be
      assessed using cell-based and cell-free assays. Acute or chronic systemic
      inflammation and the metabolic syndrome appear to render HDL proinflammatory. In
      contrast, statins and experimental agents such as apolipoprotein A-1 mimetics
      render HDL more anti-inflammatory. Functional characterization of HDL is a
      promising method for enhanced assessment of cardiovascular risk and effectiveness
      of risk reduction.

PMID- 16286162
TI  - The dying stem cell hypothesis: immune modulation as a novel mechanism for
      progenitor cell therapy in cardiac muscle.
AB  - Stem cell transplantation after myocardial infarction has been claimed to restore
      cardiac function, but the underlying mechanism remains unclear. A minority of
      transplanted cells become adherent in heart tissue and contribute to
      neovascularization, whereas many donor cells die from apoptosis. We propose that
      apoptosis of transplanted cells modulates local tissue reactions. Apoptotic cells
      impact on immune reactivity by down-regulating innate and adaptive immunity,
      deactivating macrophages and dendritic cells, and stimulating regulatory T cells.
      This leads to reduced scar formation, repressed myocardial apoptosis, and
      improved cardiac outcome.

PMID- 16286163
TI  - Efficacy and safety of fasudil in patients with stable angina: a double-blind,
      placebo-controlled, phase 2 trial.
AB  - OBJECTIVES: This study sought to evaluate the efficacy and safety of fasudil, an
      orally available rho kinase inhibitor, in patients with stable angina.
      BACKGROUND: Several small, non-placebo-controlled trials suggest that fasudil
      reduces myocardial ischemia in patients with stable or vasospastic angina.
      METHODS: In a multicenter, double-blind, placebo-controlled, randomized trial,
      the efficacy and safety of fasudil were evaluated in stable angina patients. Of
      the 206 patients screened, 84 patients with reproducible exercise times were
      randomized 1:1 to fasudil or placebo. Nitroglycerin as needed and a beta- or
      calcium-channel blocker were allowed. Fasudil or matching placebo was force
      titrated from 20 mg three times daily to 80 mg twice daily with 20 mg twice-daily
      increments every two weeks. Symptom-limited exercise testing was performed after
      two, four, six, and eight weeks of treatment. RESULTS: At peak, exercise duration
      was significantly improved at all visits in both groups, although exercise
      duration was numerically greater in patients receiving fasudil versus those
      receiving placebo. Time to > or =1 mm ST-segment depression was increased with
      fasudil at both peak and trough compared with placebo (172.1 s vs. 44.0 s, p =
      0.001, and 92.8 s vs. 26.4 s, p = 0.02, respectively). Fasudil improved Seattle
      Angina Questionnaire scores. No significant differences in Canadian
      Cardiovascular Society class, time to angina, or frequency of angina or
      nitroglycerin use were noted between groups. Fasudil did not affect heart rate or
      blood pressure, and was well tolerated. CONCLUSIONS: Fasudil up to 80 mg three
      times daily significantly increased the ischemic threshold of angina patients
      during exercise with a trend toward increased exercise duration. Further
      investigation of fasudil doses >80 mg three times daily is indicated.

PMID- 16286164
TI  - A blinded, randomized, placebo-controlled trial of percutaneous laser myocardial
      revascularization to improve angina symptoms in patients with severe coronary
      disease.
AB  - OBJECTIVES: This study was a randomized, patient- and evaluator-blinded, placebo
      controlled trial in patients treated using percutaneous myocardial laser
      revascularization. BACKGROUND: Previous studies using similar therapies have been
      confounded by placebo bias. METHODS: A total of 298 patients with severe angina
      were randomly assigned to receive low-dose or high-dose myocardial laser channels
      or no laser channels, blinded as a sham procedure. The primary end point was the
      change in exercise duration from baseline examination to six months. RESULTS: The
      incidence of 30-day death, stroke, myocardial infarction, coronary
      revascularization, or left ventricular perforation occurred in two patients in
      the placebo, eight patients in the low-dose, and four patients in the high-dose
      groups (p = 0.12); 30-day myocardial infarction incidence was higher in patients
      receiving either low-dose or high-dose laser (nine patients) compared with
      placebo (no patients, p = 0.03). At six months, there were no differences in the
      change in exercise duration between those receiving a sham (28.0 s, n = 100), low
      dose laser (33.2 s, n = 98), or high-dose laser (28.0 s, n = 98, p = 0.94)
      procedure. There were also no differences in the proportion of patients improving
      to better than Canadian Cardiovascular Society class III angina symptoms at six
      months. The follow-up visual summed stress single-photon-emission computed
      tomography scores were not significantly different from baseline in any group and
      were no different between groups. The modest improvement in angina symptoms
      assessed by the Seattle Angina Questionnaire also was not statistically different
      among the arms. CONCLUSIONS: Treatment with percutaneous myocardial laser
      revascularization provides no benefit beyond that of a similar sham procedure in
      patients blinded to their treatment status.

PMID- 16286165
TI  - Platelet reactivity in patients and recurrent events post-stenting: results of
      the PREPARE POST-STENTING Study.
AB  - OBJECTIVES: We investigated the relation of high ex vivo platelet reactivity,
      rapid fibrin generation, and high thrombin-induced clot strength to postdischarge
      ischemic events in patients undergoing percutaneous coronary intervention (PCI).
      BACKGROUND: High platelet reactivity and rapid fibrin generation may affect the
      incidence of ischemic events after PCI. However, limited data is available to
      link these ex vivo markers to the occurrence of events. METHODS: We measured
      platelet reactivity to adenosine diphosphate (ADP) by light transmittance
      aggregometry (LTA) in patients undergoing PCI (n = 192). Clot strength, a measure
      of thrombin-induced fibrin and platelet interactions, and the time to initial
      fibrin generation, a marker of thrombin activity, were measured by
      thrombelastography. The relation of these measurements to ischemic event
      occurrence was prospectively examined over six months. RESULTS: A total of 100%
      and 84% of patients were on aspirin and clopidogrel therapy, respectively, at the
      time of the initial event. Posttreatment ADP-induced aggregation by LTA (63 +/-
      12% vs. 56 +/- 15%, p = 0.02) and clot strength (MA) were higher (74 +/- 5 mm vs.
      65 +/- 4 mm, p < 0.001) and time to initial fibrin generation was shorter (4.3 +/
      1.3 min vs. 5.9 +/- 1.5 min, p < 0.001) in patients with events (n = 38). The
      event rates in the highest quartiles of LTA and MA were 32% and 58%,
      respectively. CONCLUSIONS: High platelet reactivity and clot strength, and rapid
      fibrin formation are novel risk factors for ischemic events after PCI. Clot
      strength is more predictive than ADP-induced platelet aggregation and may explain
      the occurrence of events despite treatment with cyclooxygenase-1 and P2Y12
      inhibitors.

PMID- 16286166
TI  - Clopidogrel effect on platelet reactivity in patients with stent thrombosis:
      results of the CREST Study.
AB  - OBJECTIVES: We investigated whether patients who suffered subacute stent
      thrombosis (SAT) have higher post-treatment reactivity than those who do not
      encounter stent thrombosis. BACKGROUND: High post-treatment platelet reactivity
      has been reported after coronary stenting after clopidogrel therapy and may be an
      important factor in the occurrence of SAT. METHODS: We identified patients with
      SAT treated at two tertiary care centers over a 1.5-year period. Light
      transmittance aggregation induced by adenosine diphosphate (ADP) and arachidonic
      acid, total and activated glycoprotein (GP) IIb/IIIa after stimulation with ADP,
      and vasodilator-stimulated phosphoprotein phosphorylation levels to measure P2Y12
      receptor inhibition were determined (n = 20) and compared with an age-matched
      group of patients without SAT (n = 100). High post-treatment platelet reactivity
      was defined as >75th percentile ADP-induced aggregation in the group without SAT.
      RESULTS: The SAT patients had higher mean platelet reactivity than those without
      SAT by all measurements (p < 0.05): 49 +/- 4% versus 33 +/- 2% for 5 micromol/l
      ADP-induced aggregation and 65 +/- 3% versus 51 +/- 2% for 20 micromol/l ADP
      induced aggregation (p < 0.001), 69 +/- 5% versus 46 +/- 9% for P2Y12 reactivity
      ratio (p = 0.03), and 138 +/- 19 mean fluorescence intensity (MFI) versus 42 +/-
      4 MFI for stimulated GP IIb/IIIa expression (p < 0.001). Of patients with SAT,
      60% had high platelet reactivity. CONCLUSIONS: High post-treatment platelet
      reactivity and incomplete P2Y12 receptor inhibition are risk factors for SAT.
      Measures to uniformly determine platelet reactivity after coronary stenting and
      treatment strategies to improve P2Y12 receptor inhibition in patients with high
      post-treatment platelet reactivity should be further investigated.

PMID- 16286167
TI  - Triple versus dual antiplatelet therapy after coronary stenting: impact on stent
      thrombosis.
AB  - OBJECTIVES: We evaluated safety and efficacy of triple antiplatelet therapy with
      aspirin, clopidogrel, or ticlopidine and cilostazol after coronary stenting.
      BACKGROUND: Triple antiplatelet therapy might have beneficial effect to prevent
      thrombotic complications in patients undergoing coronary stenting. METHODS:
      Patients undergoing successful coronary stenting were divided into dual
      antiplatelet therapy (aspirin plus clopidogrel or ticlopidine, group I, n =
      1,597) and triple antiplatelet therapy (aspirin plus clopidogrel or ticlopidine
      plus cilostazol, group II, n = 1,415) groups. The primary end point included
      death, myocardial infarction, target lesion revascularization, or stent
      thrombosis within 30 days. The secondary end point was side effects of study
      drugs, including major bleeding, vascular complication, hepatic dysfunction, and
      hematological complications. RESULTS: Multi-vessel stenting and the use of long
      stents were more prevalent in group II than in group I. The primary end point was
      0.8% in group I and 0.3% in group II (p = 0.085). Stent thrombosis within 30 days
      was significantly lower in group II (n = 1, 0.1%) than in group I (n = 9, 0.5%; p
      = 0.024). The independent predictors of stent thrombosis were primary stenting
      (odds ratio [OR] 7.9, 95% confidence interval [CI] 2.0 to 30.8, p = 0.003) and
      triple therapy (OR 0.12, 95% CI 0.015 to 0.98, p = 0.048). The overall adverse
      drug effects, including major bleeding, neutropenia, and thrombocytopenia, were
      no different between two groups (1.8% vs. 2.6%, p = 0.104). CONCLUSIONS: Compared
      with the dual antiplatelet regimen, triple antiplatelet therapy seemed to be more
      effective in preventing thrombotic complications after stenting without an
      increased risk of side effects. Triple antiplatelet therapy might be safely
      applied in patients or lesions with a high risk of stent thrombosis.

PMID- 16286168
TI  - The influence of race on health status outcomes one year after an acute coronary
      syndrome.
AB  - OBJECTIVES: The goal of this study was to compare health status (symptoms,
      function, and quality of life) outcomes of whites and blacks one year after an
      acute coronary syndrome (ACS). BACKGROUND: Although racial differences in the use
      of angiography and revascularization after ACS are known to exist, differences in
      health status outcomes have not been described. METHODS: We conducted a
      prospective registry of 1,159 consecutive ACS patients treated between February
      1, 2000 and October 31, 2001. One-year health status was quantified with the
      Seattle Angina Questionnaire (SAQ) and Short Form-12 Physical Component Score (SF
      12 PCS). Multivariable models were used to adjust for racial differences in
      sociodemographic, clinical, and treatment characteristics. RESULTS: Mortality
      rates were similar among the 196 black and 963 white patients (7.1% vs. 7.0%, p =
      0.93); 81 died during follow-up, and 199 (17%) could not be interviewed. At one
      year, blacks had a higher prevalence of angina (43.4% vs. 27.1%), worse quality
      of life (SAQ score = 70.6 +/- 28.3 vs. 83.9 +/- 20.8), and poorer physical
      function (SF-12 PCS = 36.8 +/- 12.3 vs. 43.2 +/- 11.4; p < 0.0001 for all).
      Multivariable models, including hospital treatments, revealed a trend for more
      angina (odds ratio 1.46 [95% confidence interval 0.91 to 2.34]) and significantly
      worse quality of life (mean difference = -7.7 +/- 2.4, p = 0.002) and physical
      function (-3.6 +/- 1.3, p = 0.005). CONCLUSIONS: Blacks have more angina, worse
      quality of life, and worse physical function one year after an ACS than do
      whites. Closer surveillance of black ACS patients is needed to determine whether
      additional treatment can improve their outcomes.

PMID- 16286169
TI  - Differences in the management and prognosis of women and men who suffer from
      acute coronary syndromes.
AB  - OBJECTIVES: The purpose of this research was to determine if sex and gender
      differences in the management of acute coronary syndromes (ACS) are associated
      with differences in prognosis after ACS. BACKGROUND: Previous investigators have
      reported sex/gender differences in the management of patients with ACS, but the
      impact of these differences on prognosis is unclear. METHODS: We analyzed data
      from the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial,
      which enrolled 4,836 women and 7,726 men with ACS. Patients were classified into
      risk strata using the Thrombolysis In Myocardial Infarction (TIMI) score.
      RESULTS: Women underwent fewer invasive procedures including angiography,
      angioplasty, and coronary artery bypass graft (CABG) surgery (47.6% vs. 60.5%; p
      = 0.0001) compared to men. No significant differences in cardiovascular death,
      myocardial infarction (MI), or stroke were observed (9.8% vs. 10.9%; p = 0.04),
      although women were more likely than men to develop refractory ischemia and to be
      rehospitalized for chest pain during follow-up (16.6% vs. 13.9%; p = 0.0001).
      These differences were particularly evident among TIMI high-risk women. A
      significant interaction between TIMI risk and gender for the outcome of
      refractory angina and rehospitalization for angina was present. CONCLUSIONS:
      Compared to men, high-risk women with ACS undergo less coronary angiography,
      angioplasty, and CABG surgery, and while they do not have higher incidence
      cardiovascular death, recurrent MI, or stroke, they suffer an increased rate of
      refractory ischemia and rehospitalization. All high-risk women and men with ACS
      should receive optimal medical management, and be considered for coronary
      angiography with possible revascularization if their coronary anatomy warrants
      it.

PMID- 16286170
TI  - Gender, race, and cardiac care: why the differences?

PMID- 16286171
TI  - Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta
      regression analysis.
AB  - OBJECTIVES: This study sought to determine whether statins reduce coronary heart
      disease (CHD) risk more than other interventions that also primarily lower low
      density lipoprotein cholesterol (LDL-C). BACKGROUND: Statins have anti
      inflammatory, immunomodulatory, antithrombotic, vascular, and other non-LDL-C
      lowering effects. It is unclear whether these pleiotropic effects contribute to
      cardiovascular risk reduction beyond that expected from LDL-C reduction alone.
      METHODS: Trials published in English language journals were retrieved by
      searching Medline (1966 to October 2004), bibliographies, and the author's
      reference files. Randomized, placebo-controlled trials of interventions to
      primarily lower LDL-C of three or more years' duration in which clinical disease
      or death were primary outcomes were used. Information on sample size, treatment
      type and duration, participant characteristics at baseline, reduction in lipids,
      and outcome was independently abstracted by two authors (J.R. and N.M.) using a
      standardized protocol. Data from 5 diet, 3 bile acid sequestrant, 1 surgery, and
      10 statin trials, with 81,859 participants, were included in the CHD meta
      regression analysis. RESULTS: The regression lines for non-statin and statin
      trials were similar and consistent with a one-to-one relationship between LDL-C
      lowering and CHD and stroke reduction over five years of treatment. CONCLUSIONS:
      The pleiotropic effects of statins do not seem to contribute an additional
      cardiovascular risk reduction benefit beyond that expected from the degree of LDL
      C lowering observed in other trials that primarily lowered LDL-C.

PMID- 16286172
TI  - At the heart of the statin benefit.

PMID- 16286173
TI  - Phenolic content of virgin olive oil improves ischemic reactive hyperemia in
      hypercholesterolemic patients.
AB  - OBJECTIVES: The goal of this study was to evaluate the effects of the phenolic
      content of virgin olive oil on endothelial reactivity. BACKGROUND: Endothelial
      dependent vasodilatation is impaired during the postprandial state, and oxidative
      stress could play a key role in its development. METHODS: Twenty-one
      hypercholesterolemic volunteers received two breakfasts, using a randomized
      sequential crossover design. Both arms received the same olive oil, but one had
      its phenolic acid content reduced from 400 to 80 ppm. Ischemic reactive hyperemia
      (IRH) was measured with a laser-Doppler procedure at baseline and 2 h and 4 h
      after oil intake. Postprandial plasma concentrations of lipid fractions,
      lipoperoxides (LPO), 8-epi prostaglandin-F(2alpha), and nitrates/nitrites (NO(x))
      were obtained at baseline and after 2 h of the fat meal. RESULTS: The intake of
      the polyphenol-rich breakfast was associated with an improvement in endothelial
      function, as well as a greater increase in concentrations of NO(x) (p < 0.001)
      and a lower increase in LPO (p < 0.005) and 8-epi prostaglandin-F2alpha (p <
      0.001) than the ones induced by the low polyphenol fat meal. A positive
      correlation was found to exist between NO(x) and enhanced endothelial function at
      the second hour (r = 0.669; p < 0.01). Furthermore, a negative correlation was
      found between IRH and LPO (r = -0.203; p < 0.05) and 8-epi prostaglandin-F2alpha
      levels (r = -0.440; p < 0.05). CONCLUSIONS: A meal containing high-phenolic
      virgin olive oil improves ischemic reactive hyperemia during the postprandial
      state. This phenomenon might be mediated via reduction in oxidative stress and
      the increase of nitric oxide metabolites.

PMID- 16286174
TI  - The relationship between blood pressure and C-reactive protein in the Multi
      Ethnic Study of Atherosclerosis (MESA).
AB  - OBJECTIVES: The goal of this study was to determine the relationship between
      resting blood pressure (BP) and C-reactive protein (CRP) in a multi-ethnic cohort
      of men and women from the Multi-Ethnic Study of Atherosclerosis (MESA).
      BACKGROUND: Several investigators have observed elevated levels of CRP in
      individuals with hypertension. Hypertension prevalence varies considerably across
      ethnic groups. Important questions remain regarding whether the relationship
      between hypertension and CRP is similar across ethnic and gender subgroups.
      METHODS: The MESA participants had CRP levels determined at the baseline clinical
      examination (N = 6,814). Hypertension, treated as a dichotomous variable
      (yes/no), was defined as a systolic or diastolic BP > or =140/90 mm Hg or a self
      reported history of hypertension and use of antihypertensive medications.
      RESULTS: The geometric mean CRP in hypertensive participants was 2.3 +/- 0.07
      mg/l compared with 1.6 +/- 0.07 mg/l among normotensive participants (p <
      0.0001). The relative difference in CRP levels in hypertensives compared with
      normotensives was similar regardless of gender (13% in men and 13% in women).
      Ethnic comparisons showed that Chinese participants had the lowest CRP
      concentration but the largest difference in CRP by hypertension status (24%).
      Caucasians and African Americans had 10% to 15% higher CRP levels with
      hypertension, whereas Hispanics had no significant difference in CRP by
      hypertension status. CONCLUSIONS: This study confirms the existence of an
      independent association between hypertension and inflammation in both men and
      women. Ethnic group differences were evident, with the strongest association
      observed in Chinese participants and no difference in CRP levels by hypertension
      status in Hispanics.

PMID- 16286175
TI  - Cardiac resynchronization therapy improves heart rate profile and heart rate
      variability of patients with moderate to severe heart failure.
AB  - OBJECTIVES: This study sought to report long-term changes of cardiac autonomic
      control by continuous, device-based monitoring of the standard deviation of the
      averages of intrinsic intervals in the 288 five-min segments of a day (SDANN) and
      of heart rate (HR) profile in heart failure (HF) patients treated with cardiac
      resynchronization therapy (CRT). BACKGROUND: Data on long-term changes of time
      domain parameters of heart rate variability (HRV) and of HR in highly symptomatic
      HF patients treated with CRT are lacking. METHODS: Stored data were retrieved for
      113 HF patients (New York Heart Association functional class III to IV, left
      ventricular ejection fraction < or =35%, QRS >120 ms) receiving a CRT device
      capable of continuous assessment of HRV and HR profile. RESULTS: The CRT induced
      a reduction of minimum HR (from 63 +/- 9 beats/min to 58 +/- 7 beats/min, p <
      0.001) and mean HR (from 76 +/- 10 beats/min to 72 +/- 8 beats/min, p < 0.01) and
      an increase of SDANN (from 69 +/- 23 ms to 93 +/- 27 ms, p < 0.001) at three
      month follow-up, which were consistent with improvement of functional capacity
      and structural changes. Different kinetics were observed among these parameters.
      The SDANN reached the plateau before minimum HR, and mean HR was the slowest
      parameter to change. Suboptimal left ventricular lead position was associated
      with no significant functional and structural improvement as well as no change or
      even worsening of HRV. The two-year event-free survival rate was significantly
      lower (62% vs. 94%, p < 0.005) in patients without any SDANN change (Delta change
      < or =0%) compared with patients who showed an increase in SDANN (Delta change
      >0%) four weeks after CRT initiation. CONCLUSIONS: Cardiac resynchronization
      therapy is able to significantly modify the sympathetic-parasympathetic
      interaction to the heart, as defined by HR profile and HRV. Lack of HRV
      improvement four weeks after CRT identifies patients at higher risk for major
      cardiovascular events.

PMID- 16286176
TI  - Cardiopulmonary exercise testing in the clinical and prognostic assessment of
      diastolic heart failure.
AB  - OBJECTIVES: This study sought to define the relative prognostic value of
      cardiopulmonary exercise testing (CPET) variables in heart failure (HF) patients
      with preserved versus reduced systolic function. BACKGROUND: Cardiopulmonary
      exercise testing has an established role in the assessment of patients with
      systolic heart failure (SHF). Two variables, peak Vo2 and, more recently, the
      VE/VCO2 slope, have been shown to be extremely valuable in risk stratification.
      However, data are lacking in terms of the prognostic value of CPET in patients
      with diastolic heart failure (DHF). METHODS: A total of 409 HF patients underwent
      CPET. Patients were divided into three groups according to the following left
      ventricular ejection fraction (LVEF) cutoffs: > or =40%, > or =45%, and > or
      =50%. The CPET response and the ability of peak VO2 and the VE/VCO2 slope to
      predict total mortality and hospitalization were examined. RESULTS: At univariate
      Cox regression analysis, both the peak VO2 and the VE/VCO2 slope were significant
      predictors in SHF and DHF. Multivariate analysis documented a similar prognostic
      power of VE/VCO2 slope and peak VO2 in all SHF groups. Conversely, in DHF
      patients, VE/VCO2 slope outnumbered peak VO2, remaining the only predictor
      regardless of LVEF. In DHF, the area under the receiver operating characteristic
      curve for the VE/VCO2slope identified a cutoff of 32.6 (74% sensitivity, 52%
      specificity), 33.1 (76% sensitivity, 62% specificity), and 33.3 (97% sensitivity,
      40% specificity) for an LVEF cutoff of > or =40%, > or =45%, and > or =50%,
      respectively. CONCLUSIONS: These results extend the clinical and prognostic
      applicability of CPET to DHF. An impairment in exercise ventilation rather than
      peak VO2 holds clinical and prognostic impact in this increasing subset of
      patients.

PMID- 16286177
TI  - Functional status in rate- versus rhythm-control strategies for atrial
      fibrillation: results of the Atrial Fibrillation Follow-Up Investigation of
      Rhythm Management (AFFIRM) Functional Status Substudy.
AB  - OBJECTIVES: The Atrial Fibrillation Follow-up Investigation of Rhythm Management
      (AFFIRM) functional status substudy aimed to test the hypothesis that functional
      status is similar in rate-control and rhythm-control strategies. BACKGROUND:
      Randomized studies, including the AFFIRM study, have failed to demonstrate
      survival benefits between rate-control and rhythm-control strategies for atrial
      fibrillation (AF). However, AF may cause functional capacity or cognitive
      impairment that might justify maintenance of sinus rhythm. METHODS: Investigators
      of the AFFIRM study enrolled 4,060 patients with AF who required long-term
      therapy and who were 65 years of age or older or who had another risk factor for
      stroke or death. New York Heart Association functional class (NYHA-FC) and
      Canadian Cardiovascular Society Angina Classification were assessed at initial
      and each follow-up visit. From 22 randomly chosen functional status substudy
      sites, 245 participants underwent 6-min walk tests and Mini-Mental State
      Examination (MMSE) at initial, two-month, and yearly visits. Patients were
      assigned randomly to rate-controlling drugs, allowing AF to persist, or rhythm
      controlling antiarrhythmic drugs, to maintain sinus rhythm. RESULTS: The NYHA-FC
      worsened with time in both rate-control and rhythm-control groups, with no
      differences between groups. Presence of AF was associated with worse NYHA-FC (p <
      0.0001). No differences were observed in Canadian Cardiovascular Society Angina
      Classification or MMSE scores. Six-minute walk distance improved over time in
      both study arms. On average, walk distance was 94 feet greater in the rhythm
      control group (adjusted p = 0.049). CONCLUSIONS: Modest improvement in 6-min walk
      distance was noted in the rhythm-control arm. Presence of AF was associated with
      worse NYHA-FC. No difference in cognitive function was detected.

PMID- 16286178
TI  - Does rhythm control improve functional status in patients with atrial
      fibrillation?

PMID- 16286179
TI  - Efficacy and safety of circumferential pulmonary vein isolation using a novel
      cryothermal balloon ablation system.
AB  - OBJECTIVES: We sought to evaluate the efficacy and safety of a novel cryothermal
      balloon ablation system in creating pulmonary vein (PV) isolation. BACKGROUND:
      Pulmonary vein isolation using standard radiofrequency ablation techniques is
      limited by procedure-related complications, such as thrombus formation and PV
      stenosis. Cryothermal ablation may reduce the risk of such complications.
      METHODS: Eight dogs underwent circumferential ablation of both superior PVs for
      either 4 or 8 min using a cryothermal balloon catheter (CryoCath Technologies
      Inc., Kirkland, Canada). Both fluoroscopy and intracardiac ultrasound (ICE)
      guided balloon and Lasso catheter positioning at the PV ostia assessed short-term
      PV integrity. In six additional dogs, long-term PV integrity was assessed by
      computed tomography at 16 weeks after ablation. RESULTS: Successful electrical
      isolation was achieved acutely in 14 of 16 (87.5%) PVs and was confirmed in one
      week survival studies in 10 of 12 (83%) PVs. Successful isolation was higher in
      the absence of any peri-balloon flow leak as seen by ICE (p = 0.015), and with
      balloon temperatures < or =-80 degrees C (p = 0.015). Cryolesions were located at
      the veno-atrial junction and were homogeneous, with intact endothelium and free
      of thrombus formation. Although limited angiographic PV narrowing was noted in
      the early follow-up period, no significant PV narrowing was seen long-term. Right
      phrenic nerve injury was seen in 50% of the animals studied at one week.
      CONCLUSIONS: This novel cryothermal balloon ablation system is effective for
      isolating PVs, but injury to the right phrenic nerve was noted in this early
      experience. Further studies are needed to assess the long-term efficacy and
      safety of this technique.

PMID- 16286180
TI  - Monitored atrial fibrillation duration predicts arterial embolic events in
      patients suffering from bradycardia and atrial fibrillation implanted with
      antitachycardia pacemakers.
AB  - OBJECTIVES: The aim of our study was to evaluate arterial embolism (AE)
      occurrence rates and predictors in patients suffering from bradycardia and
      wearing a pacemaker with antitachycardia pacing therapies. BACKGROUND: Atrial
      fibrillation (AF) is associated with a high incidence of AE. METHODS: A total of
      725 patients (360 men, age 71 +/- 11 years) were implanted with a DDDRP pacemaker
      (Medtronic AT500, Medtronic Inc., Minneapolis, Minnesota). At baseline 225
      (31.0%) patients received antiplatelet therapy and 264 (36.4%) patients received
      anticoagulation agents. RESULTS: Over a median 22-month follow-up (25th to 75th
      interquartile range 16 to 30 months), AE occurred in 14 (1.9%) patients: 7
      patients suffered a nonfatal ischemic stroke (0.6% per year), 4 patients had
      transient ischemic attack (0.34% per year), and 3 patients had embolic
      complications. Among baseline patients' characteristics, multivariate logistic
      analysis showed that embolic events are independently associated to ischemic
      heart disease (7.0 odds ratio [OR], 95% confidence interval [CI] 2.3 to 21.3, p =
      0.001), prior embolic event (7.3 OR, 95% CI 1.2 to 43.9, p = 0.029), diabetes
      (5.0 OR, 95% CI 1.2 to 15.7, p = 0.032), and hypertension (4.1 OR, 95% CI 1.1 to
      15.6, p = 0.036). The risk of embolism, adjusted for known risk factors, was 3.1
      times increased (95% CI 1.1 to 10.5, p = 0.044) in patients with device-detected
      atrial fibrillation episodes longer than one day during follow-up. CONCLUSIONS:
      In a cohort of patients with bradycardia and AF, arterial embolism was common in
      patients with ischemic cardiopathy, hypertension, diabetes mellitus, and in
      patients with known stroke risk factors. Atrial fibrillation occurrences longer
      than one day were independently associated with embolic events.

PMID- 16286181
TI  - Atrial tachycardia arising from the coronary sinus musculature:
      electrophysiological characteristics and long-term outcomes of radiofrequency
      ablation.
AB  - OBJECTIVES: We sought to describe the electrophysiological features and long-term
      outcome after radiofrequency catheter ablation (RFCA) of atrial tachycardia (AT)
      arising from the coronary sinus (CS) musculature. BACKGROUND: Atrial tachycardia
      requiring RFCA deep within the CS has been described in isolated case reports.
      However, the mechanism and exact site of origin of this tachycardia have not been
      well elucidated. METHODS: The study included 8 patients (5 men) of a consecutive
      series of 283 patients undergoing RFCA for focal AT. RESULTS: In sinus rhythm, a
      discrete potential (P) was noted after the CS atrial electrogram and during
      tachycardia, the CS (P) preceded the surface P-wave by 30 to 50 ms. The CS (P)
      always preceded the earliest electrogram in the left atrium (LA). Three
      dimensional electroanatomical mapping was available in four patients, and in one
      case it showed earliest activation in the CS with rapid spread to the proximal CS
      and then to the LA. Ablation of the AT initially attempted from the earliest site
      in the LA in three patients was unsuccessful. In all patients the tachycardia was
      safely and successfully ablated at a site 3.6 cm within the CS. There has been no
      recurrence over a follow-up of 37 +/- 13 months. CONCLUSIONS: Focal AT emanating
      deep within the CS musculature can be recognized by a discrete potential
      associated with the CS atrial signal both during sinus rhythm and tachycardia.
      Long-term success without complications can be accomplished by ablating within
      the CS in close proximity to the CS (P).

PMID- 16286182
TI  - Detection of high-risk young adults and women by coronary calcium and National
      Cholesterol Education Program Panel III guidelines.
AB  - OBJECTIVES: The purpose of this study was to investigate the classification of
      cardiovascular risk in young individuals and women according to the National
      Cholesterol Education Program (NCEP) guidelines across a continuum of coronary
      calcium scores (CCS). BACKGROUND: Current NCEP guidelines might underestimate
      cardiovascular risk in young individuals and women. METHODS: The study population
      consisted of 1,611 asymptomatic individuals (67% men, mean age: 53 +/- 10 years)
      who presented to a single electron beam tomography facility for coronary artery
      calcium screening. Participants were categorized into low-risk (n = 738, 46%),
      intermediate-risk (n = 583, 36%), moderately high-risk (n = 263, 16%), and high
      risk (n = 27, 2%) according to the NCEP Panel III guidelines. RESULTS: Absence of
      calcium, CCS of 0 to 99 (mild), 100 to 399 (moderate), and > or =400 (severe),
      was observed in 572 (35%), 707 (44%), 192 (12%), and 140 (9%) of the patients,
      respectively. A high CCS percentile (> or =75th percentile) was present in 426
      (26%) individuals. Overall, 59% and 78% of participants with CCS > or =400 and
      CCS > or =75th percentile were not identified as high risk and candidates for
      pharmacotherapy on the basis of NCEP categories. Furthermore, women as well as
      young individuals were less likely to be considered candidates for
      pharmacotherapy compared with men and older individuals in each CCS category.
      CONCLUSIONS: The NCEP guidelines seem to underestimate cardiovascular risk in
      young asymptomatic individuals and women. For these individuals, assessment of
      plaque burden might provide incremental value to global risk assessment.

PMID- 16286183
TI  - Acute hemodynamic effects of pacing in patients with Fontan physiology: a
      prospective study.
AB  - OBJECTIVES: The purpose of this research was to assess the hemodynamic response
      to atrial, ventricular, and dual-chamber pacing in patients with Fontan
      physiology. BACKGROUND: Bradycardia, due to sinus node dysfunction or
      atrioventricular (AV) block, with need for pacing, is common after the Fontan
      operation. The optimal pacing mode for Fontan patients is unknown, but is
      critical, as hemodynamic aberrancies may cause severe clinical deterioration. We
      hypothesized that AV synchrony is vital for maximizing Fontan hemodynamics.
      METHODS: A cross-over trial was conducted with 21 patients (age 2 to 18 years,
      median 4 years; male patients = 13) in the intensive care unit after a Fontan
      operation. Hemodynamic parameters, including mean left atrial pressure (LAP, in
      mm Hg), mean pulmonary artery pressure (PAP, in mm Hg), mean arterial blood
      pressure (MAP, in mm Hg), and indexed cardiac output via Fick (Qs, in l/min/m2)
      were measured with atrial, ventricular, and dual-chamber pacing. Measurements
      were made after pacing for 10 min in each mode, and a 10-min rest was given
      between each pacing maneuver. RESULTS: Asynchronous ventricular (VOO) pacing
      resulted in significantly worse hemodynamics when compared to dual-chamber (DOO)
      and atrial (AOO) pacing with a higher LAP (9.4 VOO; 6.8 DOO; 5.4 AOO) and PAP
      (15.2 VOO; 13.5 DOO; 12.7 AOO) and lower Qs (3.0 VOO; 3.5 DOO; 3.9 AOO) and MAP
      (60.1 VOO; 66.5 DOO; 67.2 AOO). CONCLUSIONS: Asynchronous ventricular pacing,
      after the Fontan procedure, has acute, adverse hemodynamic consequences (elevated
      LAP and PAP and decreased Qs and MAP).

PMID- 16286185
TI  - On the selling of pharmaceuticals.

PMID- 16286184
TI  - Human adult bone marrow mesenchymal stem cells repair experimental conduction
      block in rat cardiomyocyte cultures.
AB  - OBJECTIVES: We evaluated whether human adult bone marrow-derived mesenchymal stem
      cells (hMSCs) could repair an experimentally induced conduction block in
      cardiomyocyte cultures. BACKGROUND: Autologous stem cell therapy is a novel
      treatment option for patients with heart disease. However, detailed
      electrophysiological characterization of hMSCs is still lacking. METHODS:
      Neonatal rat cardiomyocytes were seeded on multi-electrode arrays. After 48 h,
      abrasion of a 200- to 450-microm-wide channel caused conduction block. Next, we
      applied adult hMSCs (hMSC group, n = 8), human skeletal myoblasts (myoblast
      group, n = 7), rat cardiac fibroblasts (fibroblast group, n = 7), or no cells
      (control group, n = 7) in a channel-crossing pattern. Cross-channel electrical
      conduction was analyzed after 24 and 48 h. Intracellular action potentials of
      hMSCs and cardiomyocytes were recorded. Immunostaining for connexins and
      intercellular dye transfer (calcein) assessed the presence of functional gap
      junctions. RESULTS: After creation of conduction block, two asynchronously
      beating fields of cardiomyocytes were present. Application of hMSCs restored
      synchronization between the two fields in five of eight cultures after 24 h.
      Conduction velocity across hMSCs (0.9 +/- 0.4 cm/s) was approximately 11-fold
      slower than across cardiomyocytes (10.4 +/- 5.8 cm/s). No resynchronization
      occurred in the myoblast, fibroblast, or control group. Intracellular action
      potential recordings indicated that conduction across the channel presumably
      occurred by electrotonic impulse propagation. Connexin-43 was present along
      regions of hMSC-to-cardiomyocyte contact, but not along regions of cardiomyocyte
      to-myoblast or cardiomyocyte-to-fibroblast contact. Calcein transfer from
      cardiomyocytes to hMSCs was observed within 24 h after co-culture initiation.
      CONCLUSIONS: Human mesenchymal stem cells are able to repair conduction block in
      cardiomyocyte cultures, probably through connexin-mediated coupling.

PMID- 16286186
TI  - Vascular dysfunction in Chinese vegetarians: an apparent paradox?

PMID- 16286187
TI  - Cardiac autonomic activity in patients with transient left ventricular apical
      ballooning.

PMID- 16286188
TI  - Impact of stent fractures following femoropopliteal stenting.

PMID- 16286189
TI  - Bridging the resource gap in heart failure expertise and management: the
      underacknowledged role of nurse specialists.

PMID- 16286191
TI  - Echocardiographic findings in patients with arrhythmogenic right ventricular
      cardiomyopathy/dysplasia.

PMID- 16286193
TI  - Safety of dobutamine contrast stress echocardiography.

PMID- 16286194
TI  - An organizational framework for the AMI ACC-GAP Project.

PMID- 16286196
TI  - Correcting the Class II subdivision malocclusion.

PMID- 16286197
TI  - Buccal corridor spaces, arch form, and smile esthetics.

PMID- 16286198
TI  - One-phase versus 2-phase treatment.

PMID- 16286199
TI  - Twenty-five percent is not enough.

PMID- 16286201
TI  - ABO giveaway.

PMID- 16286202
TI  - LeFort I maxillary advancement: 3-year stability and risk factors for relapse.
AB  - INTRODUCTION: The objectives of this retrospective cephalometric study were to
      assess the amount, direction, and timing of postoperative changes after LeFort I
      maxillary advancement, and to identify risk factors for skeletal relapse.
      METHODS: The material was selected from the files at the Department of
      Orthodontics, University of Oslo, and comprised 43 patients who underwent 1-piece
      LeFort I advancement as the only surgical procedure from 1990 to 1998. All
      patients were followed for 3 years by using a strict data collection protocol.
      Lateral cephalograms were obtained before surgery and at 5 times after surgery.
      RESULTS: A mean relapse of 18% of the surgical advancement occurred. In 14% of
      the patients, clinically significant skeletal relapse (> or = 2 mm) was observed.
      Most (89%) postoperative change occurred during the first 6 months after surgery.
      Skeletal relapse increased significantly with degree of surgical advancement (P =
      .001) and degree of inferior repositioning of the anterior maxilla (P = .004)
      (linear regression analysis). At the end of follow-up, overjet and overbite were
      within clinically acceptable ranges for all patients. CONCLUSIONS: Maxillary
      advancement with a 1-piece LeFort I osteotomy is a relatively stable procedure.
      Identified risk factors for horizontal relapse were degree of surgical
      advancement and degree of inferior repositioning of anterior maxilla.

PMID- 16286203
TI  - Retrospective analysis of long-term stable and unstable orthodontic treatment
      outcomes.
AB  - INTRODUCTION: The purpose of this study was to compare groups of patients with
      the most stable and the most unstable treatment results as rated by the peer
      assessment rating (PAR) index to identify factors associated with stability. All
      factors with significant crude odds ratios were investigated to create a multiple
      logistic regression model that could be used to predict stability. METHODS: The
      sample of 86 patients (30 male, 56 female), from the post-retention archives at
      the University of Washington, was not restricted to specific malocclusion types
      or treatment modalities with the exception of Angle Class III patients, who were
      excluded. The sample was divided into 2 groups, stable (n = 45) and unstable (n =
      41), based on post-retention unweighted PAR scores and PAR score changes between
      posttreatment and post-retention. Model and radiographic measurements were made
      before treatment, after treatment, and after retention (average 14.4 years).
      RESULTS: The results showed that male sex and a sustained period of growth were
      related, and both were associated with increased instability. The initial
      severity of malocclusion, as graded by the PAR index and the irregularity index,
      was negatively correlated with post-retention stability-ie, patients with more
      severe index scores before treatment tended to be less stable. Differences in
      American Board of Orthodontics scores after treatment were diminished after
      retention. CONCLUSIONS: The factors associated with predicting stability were
      pretreatment arch length, pretreatment PAR score, molar classification, and sex.

PMID- 16286204
TI  - Occlusal perceptions of children seeking orthodontic treatment: impact of
      ethnicity and socioeconomic status.
AB  - INTRODUCTION: With the growth of orthodontic intervention at younger ages and
      increased interest in improving dentofacial appearance among the general public,
      it is important to assess whether demand for treatment is uniform across ethnic
      and socioeconomic groups. METHODS: This study compared 3 groups of children who
      varied by location, payment source, and ethnicity. The sample consisted of 150
      children in the Bronx, NY, and 100 in Seattle, Wash, who were undergoing or
      anticipating orthodontic treatment in publicly funded dental clinics. Ethnic
      minorities comprised 69% and 92%, respectively, of these groups. The third group
      consisted of 84 children in Seattle, Anchorage (Alaska), and Chicago who had
      sought treatment by private practitioners; ethnic minorities comprised 22% of
      this group. Data were collected from children and parents or guardians by
      questionnaires. RESULTS: Desire for treatment was higher among children in the
      publicly funded clinics and among black children than whites or Asian Americans.
      Children in publicly funded clinics rated themselves as having worse occlusions
      as determined by anterior crowding, overbite, overjet, diastema, and open bite.
      Children in the Bronx clinic accepted a wider range of occlusion as attractive.
      Stage of treatment affected judgments of attractiveness. Vicarious experience
      with orthodontics through parents or siblings made children more tolerant of
      dentofacial disharmony, with more favorable ratings of malocclusion in this group
      than among children who had no family experience with orthodontics. Hispanic and
      mixed-ethnicity children rated themselves more negatively on all dimensions.
      CONCLUSIONS: These results suggest that both socioeconomic status and ethnicity
      play roles in children's desire for treatment, self-assessed need, and judgments
      of esthetics. A clinician's sensitivity to such differences can improve patient
      cooperation with treatment.

PMID- 16286205
TI  - Relationship between temporomandibular joint internal derangement and facial
      asymmetry in women.
AB  - INTRODUCTION: Internal derangement (ID) of the temporomandibular joint (TMJ) can
      cause facial asymmetry. The purposes of this study were to analyze the
      relationship between facial asymmetry and TMJ ID by using posteroanterior
      cephalometric variables, and to compare the findings with the results of magnetic
      resonance imaging (MRI). METHODS: The sample consisted of women seeking
      orthodontic treatment at Seoul National University Dental Hospital who had
      routine posteroanterior cephalograms and bilateral MRIs of the TMJ. To eliminate
      the influence of condylar hyperplasia on facial asymmetry, only those with SNB
      angles less then 78 degrees were selected (n = 63). They were classified into 5
      groups according to the results of the MRI: bilateral normal disk position,
      unilateral normal TMJ and contralateral disk displacement with reduction (DDR),
      bilateral DDR, unilateral DDR and contralateral disk displacement without
      reduction (DDNR), and bilateral DDNR. Fourteen variables from posteroanterior
      cephalograms were analyzed with 1-way ANOVA to evaluate differences among the 5
      groups. RESULTS: Subjects with TMJ ID of greater severity on the unilateral side
      had shorter ramal height compared with those with bilateral normal or bilateral
      DDR or bilateral DDNR. In addition, the mandibular midpoint deviated toward the
      side where the TMJ ID was more advanced. CONCLUSIONS: Subjects with a more
      degenerated TMJ on the unilateral side might have facial asymmetry that does not
      come from condylar or hemi-mandibular hyperplasia.

PMID- 16286206
TI  - Prevention of enamel demineralization: an in-vitro study using light-cured filled
      sealant.
AB  - INTRODUCTION: Enamel demineralization is an undesirable side effect of
      orthodontic treatment with fixed appliances. The purpose of this in-vitro study
      was to evaluate the efficacy of applying a light-cured filled sealant onto the
      buccal tooth surfaces to prevent demineralization. METHODS: Fifty extracted human
      third molars were allocated to 1 of 5 groups: (1) enamel surface untreated
      (control); (2) surface etched; (3) fluoride varnish applied; (4) enamel etched
      and coated with a light-cured, unfilled sealant (control sealant); and (5) enamel
      etched and coated with a light-cured, filled sealant (Pro Seal, Reliance
      Orthodontic Products, Itasca, Ill). The enamel surface of each specimen was
      brushed for 15,000 strokes with nonfluoride toothpaste slurry with a piston
      action brushing machine under a standardized load. All samples were then cycled
      for 14 days through a daily procedure of demineralization for 6 hours and
      remineralization for 17 hours. Then the teeth were sectioned and evaluated
      quantitatively by cross-sectional microhardness testing. RESULTS:
      Demineralization in the Pro Seal group was significantly less (P < .05) than in
      the other groups. Teeth treated with fluoride varnish exhibited 30% less
      demineralization than the control teeth, the enamel-etched teeth, and the teeth
      treated with a light-cured, unfilled sealant (P < .05). CONCLUSIONS: Pro Seal can
      be considered for use as a preventive method to reduce enamel demineralization
      adjacent to orthodontic attachments, particularly in patients who exhibit poor
      compliance with oral hygiene and home fluoride use.

PMID- 16286207
TI  - The effect of topical fluorides on decalcification in patients with fixed
      orthodontic appliances: a systematic review.
AB  - INTRODUCTION: Decalcification is a significant problem during fixed orthodontic
      treatment. Topical Fluorides can reduce or eliminate the problem, but the
      relative effectiveness of different treatments or combinations of topical
      fluoride preparations is unknown. This systematic review was undertaken to
      determine the effectiveness of topical fluoride preparations in preventing
      decalcification during fixed orthodontic treatment. METHODS: A wide search of
      published and unpublished material in any language was undertaken by using
      general and specialist databases; key dental journals were searched by hand.
      Predefined inclusion criteria based on objective outcome measures of
      decalcification, duration of treatment, presence of a comparison group, and study
      design were applied to determine study selection. Included studies were double
      extracted onto pre-designed data extraction sheets. RESULTS AND CONCLUSIONS: By
      screening titles and abstracts, we identified 143 articles; after the inclusion
      criteria were applied, 7 reports (of 6 studies) remained. Differences in the
      methodologies and reporting made statistical analysis impossible. However, the
      use of topical fluorides in addition to fluoride toothpaste reduced the incidence
      of decalcification in populations with both fluoridated and non-fluoridated water
      supplies. Different preparations and formats appear to decrease decalcification,
      but there was no evidence that any 1 method was superior. There was some evidence
      that the potency of fluoride preparations might be important.

PMID- 16286208
TI  - Evaluation of Class II treatment by cephalometric regional superpositions versus
      conventional measurements.
AB  - INTRODUCTION: The aims of this study were (1) to evaluate cephalometric changes
      in subjects with Class II Division 1 malocclusion who were treated with headgear
      (HG) or Frankel function regulator (FR) and (2) to compare findings from regional
      superpositions of cephalometric structures with those from conventional
      cephalometric measurements. METHODS: Cephalographs were taken at baseline, after
      1 year, and after 2 years of 65 children enrolled in a prospective randomized
      clinical trial. The spatial location of the landmarks derived from regional
      superpositions was evaluated in a coordinate system oriented on natural head
      position. The superpositions included the best anatomic fit of the anterior
      cranial base, maxillary base, and mandibular structures. RESULTS: Both the HG and
      the FR were effective in correcting the distoclusion, and they generated enhanced
      differential growth between the jaws. Differences between cranial and maxillary
      superpositions regarding mandibular displacement (Point B, pogonion, gnathion,
      menton) were noted: the HG had a more horizontal vector on maxillary
      superposition that was also greater (.0001 < P < .05) than the horizontal
      displacement observed with the FR. This discrepancy appeared to be related to (1)
      the clockwise (backward) rotation of the palatal and mandibular planes observed
      with the HG; the palatal plane's rotation, which was transferred through the
      occlusion to the mandibular plane, was factored out on maxillary superposition;
      and (2) the interaction between the inclination of the maxillary incisors and the
      forward movement of the mandible during growth. CONCLUSIONS: Findings from
      superpositions agreed with conventional angular and linear measurements regarding
      the basic conclusions for the primary effects of HG and FR. However, the results
      suggest that inferences of mandibular displacement are more reliable from
      maxillary than cranial superposition when evaluating occlusal changes during
      treatment.

PMID- 16286209
TI  - Comparative study of the maturation of permanent teeth in subjects with vertical
      and horizontal growth patterns.
AB  - INTRODUCTION: The purpose of this research was to compare the maturation stage of
      permanent teeth in subjects with vertical and horizontal growth patterns.
      METHODS: Lateral cephalograms of 256 subjects were reviewed, and subjects were
      classified according to facial growth pattern. The 30 subjects with the greatest
      predominance of vertical growth and the 30 with the greatest predominance of
      horizontal growth were selected; these subjects comprised the vertical and
      horizontal groups, respectively. Panoramic radiographs of the subjects obtained
      at 8 years of age were used to evaluate the maturation of the permanent teeth,
      expressed by the dental age. Comparisons between groups were made with
      independent t tests. RESULTS: A statistically significant difference was noted
      between the dental ages of the vertical and horizontal groups, with the vertical
      group having a more advanced dental age. CONCLUSION: Subjects with vertical
      growth patterns should be expected to mature dentally earlier than horizontal
      growers.

PMID- 16286210
TI  - Evaluation of the accuracy of digital model analysis for the American Board of
      Orthodontics objective grading system for dental casts.
AB  - INTRODUCTION: In 1999, after 3 years of field testing, the American Board of
      Orthodontics (ABO) implemented a grading system for posttreatment orthodontic
      models and panoramic radiographs, to make the phase III examination both fair and
      objective. In the ABO's objective grading system, 7 occlusal criteria (tooth
      alignment, vertical positioning of marginal ridges, buccolingual inclination of
      posterior teeth, occlusal relationship, occlusal contacts, overjet, and
      interproximal contacts) are measured on plaster models to assess a patient's
      final occlusion. To date, no study has evaluated the ABO grading system for use
      on digital models. The purpose of this study was to determine whether digital
      models can be used with reasonable accuracy and reliability for assessing
      patients' final occlusions. METHODS: Plaster and digital (OrthoCAD, Cadent Inc,
      Carlstadt, NJ) posttreatment models of 24 patients were gathered from the
      postgraduate orthodontic clinic at Columbia University School of Dental and Oral
      Surgery. The plaster models were scored by using the ABO measuring gauge and the
      7 criteria of the ABO grading system. A second analysis was done on the digital
      models. To determine interexaminer error, a fourth-year dental student at
      Columbia University served as a second examiner and repeated all the analyses.
      RESULTS: The means of the total score and those for marginal ridges, occlusal
      contacts, occlusal relationships, overjet, and interproximal contacts were not
      significantly different between plaster and digital models. However, the means
      for alignment and buccolingual inclination were significantly different. In
      addition, the scorings of 2 examiners differed for the 2 methods. CONCLUSIONS:
      This finding suggests that alignment and buccolingual inclination should be
      reevaluated with both methods, and adequate calibration of the examiners is
      essential to achieve repeatability in both methods. Digital models might be
      acceptable for use in the ABO model examination.

PMID- 16286211
TI  - Porcelain surface treatment by laser for bracket-porcelain bonding.
AB  - INTRODUCTION: The purposes of this study were to investigate the effect of laser
      irradiation on the adhesion of brackets bonded to feldspathic porcelain and to
      compare it with brackets bonded with conventional techniques. METHODS: One
      hundred porcelain-fused-to-metal specimens were divided into 10 groups of 10. The
      treatment groups were sandblasted (SB), sandblasted with silane (SB+S),
      orthophosphoric acid (OFA), orthophosphoric acid with silane (OFA+S),
      hydrofluoric acid (HFA), hydrofluoric acid with silane (HFA+S), laser etched (L),
      laser etched with silane (L+S), glazed (Control 1/C1), and deglazed (Control
      2/C2). Five other specimens were irradiated by 2-, 3-, 5-, 10-, and 15-watt
      superpulse carbon dioxide (CO2) laser for 20 seconds and examined by scanning
      electron microscopy. Metal brackets were bonded with a self-cure composite
      material and the specimens were stored in water at 37 degrees C for 24 hours and
      then thermocycled in water baths between 5 degrees C and 55 degrees C 500 times.
      Bond strength was determined in megapascals (MPa) by shear test at 1 mm/minute
      crosshead speed. Bond failure modes were observed under stereomicroscope. For the
      statistical analysis, 1-way ANOVA and Tamhane post hoc test were used. RESULTS:
      Statistical analysis showed significant differences between the groups at the .05
      level. The HFA+S group yielded the highest mean strength (15.07 +/- 1.44). This
      was followed by SB+S (13.81 +/- 2.00), HFA (10.78 +/- 0.62), OFA+S (10.73 +/-
      1.12), L+S (8.25 +/- 0.90), L (6.26 +/- 0.58), C2 (2.45 +/- 0.54), OFA (2.36 +/-
      0.41), SB (2.04 +/- 0.41), and C1 (1.64 +/- 0.33). The bond failure modes of HFA
      and silane groups, except L+S, were cohesive in porcelain. Control groups and
      other test groups showed adhesive failure. Only irradiation by 2 watts for 20
      seconds provided a porous surface texture without cracks. CONCLUSIONS: Two
      watt/20 second superpulse CO2 laser irradiation might be an alternative
      conditioning method for pretreating ceramic surfaces. Increased bond strength can
      be achieved by silanation after CO2 laser irradiation.

PMID- 16286213
TI  - Malocclusion severity in Asian men in relation to malocclusion type and
      orthodontic treatment need.
AB  - INTRODUCTION: The purpose of this study was to assess the severity of
      malocclusion in young Asian men in relation to types of malocclusion and
      orthodontic treatment need. METHODS: Study models of 339 male army recruits (age,
      17-22 years) with no history of orthodontic treatment were assessed. The peer
      assessment rating (PAR) index was used to determine the severity of their
      malocclusions. Logistic regression and receiver operating characteristics (ROC)
      curves were performed to evaluate the PAR index in relation to treatment need
      assessed by the dental health component (DHC) and the esthetic component (EC) of
      the index of orthodontic treatment need. RESULTS: The mean PAR scores were 17,
      20, 28, and 18 for Class I, Class II Division 1, Class II Division 2, and Class
      III, respectively. PAR scores were highly correlated with DHC and EC scores (P <
      .001). An increase of 1 point in the PAR score significantly increased the
      likelihood of orthodontic treatment need for dental-health reasons or esthetic
      impairment (by 1.17 times [95% CI 1.13-1.21] or 1.25 times [95% CI 1.19-1.31]).
      The areas under the ROC curves for PAR index were 84% and 94% for the DHC and EC
      assessments, respectively, suggesting that PAR scores were better predicators of
      esthetic than dental health impairment for assessing Asian malocclusions. The
      optimum cutoff points were PAR scores of 17 and 20 for dental health and esthetic
      impairment, respectively. CONCLUSIONS: Class II malocclusions were more severe
      than Class I or III in Asian men. Malocclusions with definite treatment need had
      PAR scores that were significantly greater than those with borderline, little, or
      no need. ROC curves showed that the PAR index had an acceptable level of validity
      with the professional assessment of orthodontic treatment need in Asian
      malocclusions. The optimum cutoff PAR scores were 17 and 20 in relation to DHC
      and EC assessment, respectively. The PAR index was more predictive of esthetic
      than dental health need.

PMID- 16286212
TI  - Nd: YAG laser for debonding ceramic orthodontic brackets.
AB  - INTRODUCTION: The purpose of this study was to develop an effective method for
      debonding ceramic orthodontic brackets with a high-peak power Nd:YAG laser.
      METHODS: Two types of ceramic brackets (single crystal and polycrystalline) were
      bonded to mandibular bovine teeth with 2 types of bonding resins (4-META/MMA and
      Bis-GMA). The laser was applied to 2 points on each bracket, each with a 1-pulse
      per-second shot. Bond strength and thermal effects of the laser on the dentin
      surface were assessed at 3 laser energy levels: 1.0, 2.0, and 3.0 joules (J).
      Shear tests were performed on the irradiated test group and on a nonirradiated
      control group. ANOVA was used to determine significant differences. RESULTS: The
      shear test (P < .05) showed that every specimen in the 2.0-J and 3.0-J groups
      underwent a significant decrease in bonding strength compared with the
      nonirradiated group. However, the 1.0-J group did not exhibit any such
      difference. In the 2 former groups, laser irradiation alone was sufficient to
      debond some specimens. No significant difference was found between bonding
      resins. The maximum temperature rise measured on the pulpal walls at the lasing
      points was 5.1 degrees C. CONCLUSIONS: The application of a high-peak power
      Nd:YAG laser at 2.0 J or more is effective for debonding ceramic brackets.

PMID- 16286214
TI  - Cephalometric norms of Nigerian children.
AB  - INTRODUCTION: The purpose of this study was to develop cephalometric standards
      for Nigerian children. METHODS: The average values of 7 dentoskeletal angles were
      determined from standardized lateral head radiographs of 100 schoolchildren (aged
      11 to 13 years; mean, 12.6 years) in Enugu, a city in southeastern Nigeria. The
      children, born to Nigerian parents of Igbo ancestry (Igbo is 1 of the 3 major
      ethnic groups in Nigeria), were selected on the basis of a well-balanced face and
      acceptable profile, Class I occlusion with normal overjet and overbite, minor or
      no crowding or spacing, and no history of orthodontic treatment. RESULTS: There
      were no statistically significant differences in cephalometric measurements
      between boys and girls; thus, the data were combined for analysis. The mean
      values and standard deviations obtained for the measured variables were: SNA,
      85.5 degrees (+/- 4.3 degrees); SNB, 81.2 degrees (+/- 4.0 degrees); ANB, 4.3
      degrees (+/- 2.5 degrees); UI-FP, 122.8 degrees (+/- 7.5 degrees); Ll-MP, 98.8
      degrees (+/- 5.8 degrees); Ul-LI, 109.1 degrees (+/- 8.0 degrees); and FMA, 26.1
      degrees (+/- 5.0 degrees). CONCLUSIONS: Compared with the norms for other ethnic
      groups, Igbo children have a prognathic relationship of the maxilla and the
      mandible to the anterior cranial base with a tendency toward a protrusive
      skeletal pattern. The children also exhibited prominent bimaxillary proclination
      with procumbent and protrusive maxillary and mandibular incisors and a steep
      Frankfort-mandibular plane angle. The findings emphasize the need for group
      specific norms for orthodontic diagnosis and treatment planning, and provide
      cephalometric standards for Igbo children.

PMID- 16286215
TI  - Proposed reference point for 3-dimensional cephalometric analysis with cone-beam
      computerized tomography.
AB  - INTRODUCTION: The purpose of this article is to propose a reference landmark for
      use in 3-dimensional cephalometric analysis with 3-dimensional volumetric images.
      METHODS: Cone-beam computerized tomographies were obtained from 10 adolescent
      patients. They were analyzed with AMIRA software (Mercury Computer Systems,
      Berlin, Germany). RESULTS: The proposed reference point is located between both
      foramina spinosum. CONCLUSION: This point has high intrareliability and is an
      adequate landmark for use as a reference in 3-dimensional cephalometric analysis.

PMID- 16286216
TI  - Category 6: Class II Division 1 malocclusion treated with extraction of permanent
      teeth.
AB  - This case report was submitted to the American Board of Orthodontics as part of
      the board-certification process. The summary of treatment and records are
      reprinted here much as they were submitted to the board.

PMID- 16286217
TI  - Litigation, legislation, and ethics: that was then, and this is now.

PMID- 16286219
TI  - Giving children a great gift: family traditions.

PMID- 16286220
TI  - How mothers respond to their crying infant.
AB  - INTRODUCTION: The purpose of this study was to allow mothers who are at high risk
      for abusing their child to describe how they manage when their infant cries.
      METHOD: This phenomenologic qualitative study used a focus group design and semi
      structured interview format. Participants were seven low-income women with a
      child enrolled in an urban day care facility, which provided the setting for data
      collection. RESULTS: Analyses of the data revealed three themes: (a) activities
      done to pacify the infant, (b) coping mechanism, and (c) social support
      available. DISCUSSION: The results of this study indicate that activities (a) may
      include the infant, such as holding and singing, or (b) may be directed toward
      the mother, such as using headphones or leaving the room. These activities follow
      the guidelines of the American Academy of Pediatrics and are not unique. Social
      support primarily was provided at the day care facility, supplemented with
      personal relationships that are tentative. Valued informal and formal
      interactions with supportive persons provide the emotional and psychosocial
      support for this at-risk population.

PMID- 16286221
TI  - Better breathing or better living? A qualitative analysis of the impact of asthma
      medication acquisition on standard of living and quality of life in low-income
      families of children with asthma.
AB  - INTRODUCTION: Purchasing children's asthma medications places a burden on low
      income families. The objective of this study was to explore how purchasing
      children's asthma medications influenced household purchasing behavior and
      quality of life in low-income families with no drug insurance. METHOD: Seventeen
      parents residing in the Greater Toronto Area with no drug plan and with household
      incomes below 45,000 US dollars (twice the U.S. poverty level) participated. Semi
      structured interviews were conducted, emphasizing the topics of prescription
      drugs used and cost versus effectiveness; purchasing behavior and drug
      administration; effects of medication purchasing on the family; and payment
      assistance. Transcribed narratives were coded and analyzed thematically. RESULTS:
      Annual expenditures for asthma drugs were 300 US dollars to 3000 US dollars.
      Because asthma management was a high priority, foregone expenditures included
      paying for other family members' health needs, essentials (clothing, food, better
      housing), and nonessentials (recreation, vacations) and long-term investments,
      such as their child's future education and their retirement. Respondents believed
      quality of life was negatively affected. DISCUSSION: Not addressing the health
      concerns of family members, making sacrifices, and modifying investment decisions
      created sustained anxiety in families of children with asthma. Access to
      medication benefits would have a positive impact on quality of life. Health care
      providers can help to ensure that low-income families receive available
      assistance.

PMID- 16286222
TI  - Visual perceptual skills in children born with very low birth weights.
AB  - INTRODUCTION: A disproportionate number of very low birth weight (VLBW; < or
      =1500 g) children require special education services and have school-related
      problems even when they are free from major disabilities and have average
      intelligence quotient scores. Visual-perceptual problems have been suggested as
      contributors to deficits in academic performance, but few data are available
      describing specific visual-perceptual problems. This study was designed to
      identify specific visual-perceptual skills in VLBW children. METHOD: Participants
      were 92 VLBW children aged 4 through 5 years who were free from major disability
      and appropriate for gestational age at birth. The Test of Visual-Perceptual
      Skills (non-motor)-Revised was used. RESULTS: Despite intelligent quotient scores
      in the average range, the majority (63% to 78.3%) of the children performed below
      age level on all seven subscales of a normed assessment of visual perceptual
      skills. DISCUSSION: Results suggest that visual perceptual screening should be
      considered as a part of routine evaluations of preschool-aged children born
      prematurely. Early identification of specific deficits could lead to
      interventions to improve achievement trajectories for these high-risk children.

PMID- 16286223
TI  - Pediculosis capitis.
AB  - Pediculosis capitis is a worldwide public health concern. Infestation occurs most
      commonly in children, with a peak incidence between 5 to 11 years of age. The
      condition is more common in girls and less common in Black children. Direct head
      to-head contact is the most common mode of transmission. Pruritus is the most
      common symptom of infestation. The gold standard for diagnosing pediculosis
      capitis is finding a live louse or nymph in the scalp or viable egg in the scalp
      hair. Pediculicides are the most effective treatment. All household members and
      close contacts should be examined and treated concurrently if infested. The child
      should be allowed to return to school or to a child care facility after proper
      treatment. The child should be discouraged from close, direct head contact with
      others or from sharing items that have come in contact with the hair.

PMID- 16286224
TI  - Preanesthesia considerations for the nurse practitioner.
AB  - With increases in pediatric ambulatory surgery, primary health care providers
      such as nurse practitioners are being called upon to provide input about patients
      preoperatively or prior to other procedures requiring anesthesia. Because the
      anesthesia team may not meet the patient and family until the day of surgery; a
      thorough evaluation done by the primary care provider can supply the anesthesia
      team with the information required for optimal care. Such information includes a
      detailed history, including the patient's birth history, medical diagnoses,
      medications, allergies, recent laboratory test values, and the results of a
      recent physical examination. The purpose of this article is to provide primary
      care nurse practitioners with guidelines and information to consider when seeing
      their patient for a preprocedural visit.

PMID- 16286225
TI  - Anemia: diagnosis and management.
AB  - Anemia is a pathologic condition produced by a decrease in red blood cell mass or
      a decrease in the amount of hemoglobin. Anemia is a common occurrence in the
      United States. Children from some ethnic groups have a higher incidence of
      anemia, but anemia also can affect overweight children and children with chronic
      illnesses. Iron-deficiency anemia, which is the most common cause of anemia and
      can produce long-term developmental outcomes, continues to be prevalent in some
      groups of children. This article will review the procedures for taking a history,
      determining the etiology, and providing initial treatment for the anemia.

PMID- 16286226
TI  - Omalizumab: a steroid-sparing option for improving pediatric asthma management?

PMID- 16286227
TI  - Do you have consent to treat?

PMID- 16286228
TI  - Youth and tobacco use: nurses take a stand.

PMID- 16286229
TI  - Medical alert identification: a "scarlet letter" or tool for diabetes management.

PMID- 16286230
TI  - PNP role: tooting our own horns (well, it's about time!).

PMID- 16286231
TI  - Proceedings of the 9th International Conference on Primary Therapy of Early
      Breast Cancer. January 26-29, 2005. St. Gallen, Switzerland.

PMID- 16286232
TI  - Breast cancer control: signs of progress, but more work required.
AB  - Breast cancer represents 10% of the global cancer burden and there is no
      population, or population sub-group, which has yet been identified to be at a
      truly low risk of developing the disease. Mortality rates have been steadily
      growing for nearly a century in many countries and it is only during the past
      decade that there have been signs of a sustainable decrease in mortality rates in
      a number of western-lifestyle countries. This represents considerable progress in
      breast cancer control and, although different factors contribute to different
      degrees in different countries, is mainly due to increased breast awareness,
      earlier detection and the delivery of the most appropriate therapy to women with
      the disease. The failure to prevent the incidence from continuing to rise
      represents to a great extent the failure to understand the precise mechanisms of
      breast carcinogenesis and the role of risk determinants whose alteration in
      society could lead to a reduced risk of developing the disease. The declines seen
      in mortality represent a considerable success, but there is no room for
      complacency until research can impact positively on reducing incidence.

PMID- 16286233
TI  - Modelling COPD in mice.
AB  - Chronic obstructive pulmonary disease (COPD) is characterised by persistent
      airflow limitation, neutrophilic inflammation, macrophage accumulation, and the
      production of cytokines, chemokines and proteases. Cigarette smoking is the major
      cause of COPD and there is currently no satisfactory therapy to help treat
      individuals with this disease. A better understanding of the cellular and
      molecular responses triggered by cigarette smoke may provide new molecular
      targets for the development of therapeutic agents. This brief review highlights
      some of the mouse models used to define the cellular, molecular and pathological
      consequences of cigarette smoke exposure.

PMID- 16286234
TI  - What is the contribution of respiratory viruses and lung proteases to airway
      remodelling in asthma and chronic obstructive pulmonary disease?
AB  - It is well known that the lungs of asthmatics show airway wall remodelling and
      that asthma exacerbations are linked to respiratory infections. There is some
      evidence that respiratory infections in early childhood may increase the risk of
      developing asthma later in life. Chronic obstructive pulmonary disease (COPD), by
      definition, involves structural changes to the airways. However, very little is
      known about what role virus infections play in the development of this
      remodelling. This review considers the role of matrix metalloproteases and
      neutrophil elastase in remodelling, and whether the induction of proteases and
      other mediators during respiratory virus infections may contribute to the
      development of airway remodelling.

PMID- 16286235
TI  - Regulation of human airway mesenchymal cell proliferation by glucocorticoids and
      beta2-adrenoceptor agonists.
AB  - Altered rates of cell proliferation play important roles in the pathogenesis of a
      variety of conditions, including cancer, inflammation and several airway and
      cardiovascular diseases. One of the most consistently observed changes in
      asthmatic airways is an increased volume of airway smooth muscle (ASM), that has
      been explained by proliferation, hypertrophy, extracellular matrix deposition
      within the smooth muscle bundles, and more recently, the migration of mesenchymal
      precursor cells to the airways. The best characterised of these is proliferation
      of ASM cells. In vitro studies suggest that the proliferation is driven by
      various mitogens, and ECM proteins found in asthma, such as collagen type I.
      Therefore, we compared the anti-mitogenic actions of two classes of anti-asthma
      agents, the glucocorticoids and the beta2-adrenoceptor agonists, in ASM cells
      grown on collagen type I. Culture on collagen type I prevented the anti-mitogenic
      actions of glucocorticoids, but not beta2-adrenoceptor agonists. In contrast,
      glucocorticoids are efficacious in regulating ASM production of GM-CSF, whereas
      beta2-adrenoceptor agonists are without effect. Therefore, combination therapy
      may have increased efficacy over glucocorticoids alone in controlling remodelling
      events due to complementary actions of the two classes of compounds.

PMID- 16286236
TI  - The PPARgamma ligand, rosiglitazone, reduces airways hyperresponsiveness in a
      murine model of allergen-induced inflammation.
AB  - There is considerable interest in the role of peroxisome proliferator activated
      receptors (PPARs) as ligand-activated transcription factors in the airways. This
      study examines the effects of a potent synthetic PPARgamma ligand, rosiglitazone
      (RG), in a murine model of allergen-induced inflammation, to explore its
      potential regulation of airways inflammation, structure and function. C57BL/6
      mice were sensitised with ovalbumin (OVA, 50 microg i.p., days 0, 12) and
      challenged with aerosolized OVA (1% w v(-1), 30 min day(-1)) for 7 days (days 20
      26). Mice were treated with RG (5 mg kg(-1) i.p.) or vehicle during the challenge
      period. The OVA challenge induced increases in leukocyte number and MMP-2
      activity in bronchoalveolar lavage fluid and in goblet cell number in lung tissue
      obtained on Day 27. RG failed to inhibit inflammatory cell infiltration, MMP-2
      activity or goblet cell hyperplasia. Respiratory resistance in response to
      methacholine (MCh i.v.) was greater in OVA-challenged mice than saline-challenged
      mice and this airways hyperresponsiveness (AHR) was reduced by RG. However, RG
      did not affect MCh-induced contraction in isolated guinea-pig tracheal rings, nor
      did it influence the airway obstruction induced by MCh in saline-challenged mice,
      so a direct effect on airway obstruction is unlikely. These data suggest that RG
      modulates AHR in this model, by a mechanism that is also potentially independent
      of an anti-inflammatory action.

PMID- 16286237
TI  - Interleukin-17 and airway remodelling.
AB  - Interleukin (IL)-17A is emerging as important in reinforcing innate immunity by
      orchestrating sustained neutrophilic mobilisation. Even though there are
      indications of association with specific airway diseases, there is still no final
      proof that IL-17A plays a truly causative pathogenic role. There is evidence in
      mice that endogenous IL-17A contributes to the development of allergen-induced
      airway hyperresponsiveness and there is also evidence that IL-17A stimulates the
      release of several cytokines with known capacity for airway remodelling, from
      cells normally residing in the airways. New studies are required to determine
      whether these effects on local cells actually contribute to airway remodelling in
      vivo. If this is the case, then IL-17A may constitute a useful target for
      pharmacotherapeutic intervention in allergic airway disease.

PMID- 16286238
TI  - Lymphatic endothelium: an important interactive surface for malignant cells.
AB  - Endothelial cells line the vessels which transport fluid and cells throughout the
      body. Although much attention has been paid to these cells in the context of the
      blood vascular system, endothelial cells also line lymphatic vessels. Recent
      progress in identifying growth factors which drive the development of lymphatic
      vessels and molecular markers specific for lymphatics has expanded our
      understanding of the role the lymphatic system plays in human pathology.
      Techniques for purifying populations of lymphatic endothelial cells also allow
      the in vitro analysis of this unique surface to explore its role in tumour
      metastasis, immune cell function and fluid transport. This review provides a
      synopsis of the recent data pertaining to the purification and culture of
      lymphatic endothelial cells, and the interaction of tumour cells with lymphatic
      endothelium.

PMID- 16286239
TI  - The biology of vascular endothelial growth factor-B (VEGF-B).
AB  - The formation of new blood vessels (angiogenesis) is critical for both embryonic
      development and a variety of normal postnatal physiological processes. Various
      pathological processes, most notably tumour growth and chronic inflammation, are
      also known to be dependent on the new vessel formation. Amongst the variety of
      factors that contribute to the regulation of this complex process, vascular
      endothelial growth factor (VEGF or VEGF-A) is arguably the most well
      characterised. The VEGF family of growth factors is now known to comprise of VEGF
      A plus four additional members, including VEGF-B. In contrast to VEGF-A,
      surprisingly little is known about the precise biological role of VEGF-B. Unlike
      VEGF-A, which binds to the two receptor tyrosine kinases VEGFR-1 (Flt-1) and
      VEGFR-2 (Flk-1/KDR), VEGF-B binds only to VEGFR-1 and the functional significance
      of VEGFR-1 signalling has remained problematic. More recently, however, evidence
      has emerged suggesting a key role for VEGFR-1 signalling in pathological
      angiogenesis and this has raised the possibility that, like VEGF-A, VEGFR-1
      specific ligands such as VEGF-B may provide for novel therapeutic strategies
      and/or represent new therapeutic targets. Here we review current knowledge of the
      biology of VEGF-B. We note that although analysis to date, including expression
      profiling and the generation of gene targetted mice, has provided only limited
      insights, future studies using recently generated recombinant proteins and
      antagonist monoclonal antibodies should provide for a more comprehensive
      understanding.

PMID- 16286240
TI  - Fine mapping of Lvm1: a quantitative trait locus controlling heart size
      independently of blood pressure.
AB  - We have previously reported a quantitative trait locus (QTL) on rat chromosome 2
      that influences heart size independently of blood pressure (Left Ventricular Mass
      Locus 1; Lvm1). The recent release of the rat genome sequence allowed us to
      retest and refine this relatively broad QTL with a view to identifying within it
      candidate genes worthy of structural investigation. We sought to achieve this
      'fine mapping' by increasing the marker density within the interval and
      undertaking a linkage analysis in a previously defined population of F2 hybrids
      generated from inbred spontaneously hypertensive rats (SHR) of the Okamoto strain
      and Fischer rat (F344) progenitors. We were able to reconfirm and resolve Lvm1
      from its original width of approximately 45 to 15 cM. By reference to the ENSEBL
      rat genome data bank, we identified within Lvm1 27 known genes, 109 predicted
      genes and 7 pseudogenes. Of the known genes, candidates include potential
      regulators of cardiac growth, a sodium channel and calcium channel as well as the
      fibroblast growth factor 2 gene. Located nearby the Lvm1 locus was the gene for
      the angiotensin Type 1B receptor. Given the evidence that the ligand for the
      angiotensin Type 1B receptor-angiotensin II-is a potent cardiotroph, we also
      consider this gene a potential candidate. The identification of the precise
      allelic variant(s) within Lvm1 involved in the control of pressure-independent
      cardiac growth awaits further molecular studies.

PMID- 16286241
TI  - The dual adverse effects of TGF-beta secretion on tumor progression.
AB  - When a cancer escapes the growth-inhibitory effects of TGF-beta secreted by
      cancer cells themselves or by cells in the local stroma, a further adverse
      outcome for the host is the associated TGF-beta-induced suppression of anticancer
      T cell immunity. In addition to the previously described dampening of T cell
      activation and proliferation, TGF-beta markedly and directly suppresses the
      transcription of genes encoding multiple key proteins of the "cytotoxic program"
      of CD8+ CTL, such as perforin and granzymes, cytotoxins that act through the
      granule exocytosis pathway. The findings described below suggest that TGF-beta
      and its signaling pathways will be major targets for novel cancer therapeutics.

PMID- 16286242
TI  - A signaling role for dystrophin: inhibiting skeletal muscle atrophy pathways.
AB  - Skeletal muscle atrophy is a common comorbidity of cancer. The cellular signaling
      mechanisms that regulate muscle size constitute a balance of the protein
      breakdown pathways upregulated during atrophy, and the protein synthesis pathways
      that are activated during skeletal muscle hypertrophy. In this issue of Cancer
      Cell, Acharyya et al. demonstrate a new and surprising regulatory axis that is
      centered around dystrophin, the protein that is mutated in settings of muscular
      dystrophy. These data reposition dystrophin as a signaling protein and connect an
      important cellular complex required for the structural integrity of muscle to the
      pathways that modulate muscle size.

PMID- 16286243
TI  - Tetraploidy and tumor development.
AB  - In tumorigenesis, aneuploidy is frequently preceded by tetraploidy. Major issues
      include how tetraploidy arises and how cells can effectively respond to this
      state. Two recent papers address these issues. Shi and King demonstrate that
      nondisjunction of chromosomes in mitosis frequently results in tetraploidy
      through mitotic cleavage failure. Fujiwara et al. demonstrate that p53 null
      tetraploid cells are highly competent to induce tumors in nude mice. Together,
      these papers emphasize the unique hazard of tetraploidy and the fact that p53
      status has an intrinsic capacity to eliminate tetraploid cells and suppress
      tumorigenesis. This p53-dependent elimination may represent a checkpoint control.

PMID- 16286244
TI  - The tumor suppressor PP2A is functionally inactivated in blast crisis CML through
      the inhibitory activity of the BCR/ABL-regulated SET protein.
AB  - The oncogenic BCR/ABL kinase activity induces and maintains chronic myelogenous
      leukemia (CML). We show here that, in BCR/ABL-transformed cells and CML blast
      crisis (CML-BC) progenitors, the phosphatase activity of the tumor suppressor
      PP2A is inhibited by the BCR/ABL-induced expression of the PP2A inhibitor SET. In
      imatinib-sensitive and -resistant (T315I included) BCR/ABL+ cell lines and CML-BC
      progenitors, molecular and/or pharmacological activation of PP2A promotes
      dephosphorylation of key regulators of cell proliferation and survival,
      suppresses BCR/ABL activity, and induces BCR/ABL degradation. Furthermore, PP2A
      activation results in growth suppression, enhanced apoptosis, restored
      differentiation, impaired clonogenic potential, and decreased in vivo
      leukemogenesis of imatinib-sensitive and -resistant BCR/ABL+ cells. Thus,
      functional inactivation of PP2A is essential for BCR/ABL leukemogenesis and,
      perhaps, required for blastic transformation.

PMID- 16286245
TI  - TGF-beta directly targets cytotoxic T cell functions during tumor evasion of
      immune surveillance.
AB  - Tumors escape from immune surveillance by producing the immunosuppressive
      cytokine TGF-beta. However, the mechanism by which TGF-beta inhibits T cell
      mediated tumor clearance in vivo is unknown. We demonstrate that TGF-beta acts on
      cytotoxic T lymphocytes (CTLs) to specifically inhibit the expression of five
      cytolytic gene products-namely, perforin, granzyme A, granzyme B, Fas ligand, and
      interferon gamma-which are collectively responsible for CTL-mediated tumor
      cytotoxicity. Repression of granzyme B and interferon-gamma involves binding of
      TGF-beta-activated Smad and ATF1 transcription factors to their promoter regions,
      indicating direct and selective regulation by the TGF-beta/Smad pathway.
      Neutralization of systemic TGF-beta in mice enables tumor clearance with
      restoration of cytotoxic gene expression in antigen-specific CTLs in vivo. We
      suggest that TGF-beta suppresses CTL function in vivo through an anticytotoxic
      program of transcriptional repression.

PMID- 16286246
TI  - Reduction in the requirement of oncogenic Ras signaling to activation of PI3K/AKT
      pathway during tumor maintenance.
AB  - While tumors become addicted to oncogenes like Ras, the microenvironment in which
      tumor cells reside changes during tumorigenesis; the cells are surrounded
      initially by normal tissue and later by tumor tissue. Hence, we asked if Ras
      exerts its oncogenic effects through the same set of effectors during different
      stages of tumorigenesis. We now show in human cells that the Ras effector
      pathways MAPK, RalGEF, and PI3K are required to initiate tumor growth.
      Conversely, activation of the PI3K/AKT pathway replaced Ras once tumors formed,
      although other effectors were still activated independently of Ras, presumably by
      factors provided upon the establishment of a tumor microenvironment. Thus, as
      tumorigenesis progresses the addiction of cancers to their initiating oncogene is
      reduced to, at least in the case of Ras, the PI3K/AKT pathway.

PMID- 16286247
TI  - Integrative genomic and proteomic analysis of prostate cancer reveals signatures
      of metastatic progression.
AB  - Molecular profiling of cancer at the transcript level has become routine. Large
      scale analysis of proteomic alterations during cancer progression has been a more
      daunting task. Here, we employed high-throughput immunoblotting in order to
      interrogate tissue extracts derived from prostate cancer. We identified 64
      proteins that were altered in prostate cancer relative to benign prostate and 156
      additional proteins that were altered in metastatic disease. An integrative
      analysis of this compendium of proteomic alterations and transcriptomic data was
      performed, revealing only 48%-64% concordance between protein and transcript
      levels. Importantly, differential proteomic alterations between metastatic and
      clinically localized prostate cancer that mapped concordantly to gene transcripts
      served as predictors of clinical outcome in prostate cancer as well as other
      solid tumors.

PMID- 16286248
TI  - A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma
      cells with mechanisms distinct from Bortezomib.
AB  - Bortezomib therapy has proven successful for the treatment of relapsed and/or
      refractory multiple myeloma (MM); however, prolonged treatment is associated with
      toxicity and development of drug resistance. Here, we show that the novel
      proteasome inhibitor NPI-0052 induces apoptosis in MM cells resistant to
      conventional and Bortezomib therapies. NPI-0052 is distinct from Bortezomib in
      its chemical structure, effects on proteasome activities, mechanisms of action,
      and toxicity profile against normal cells. Moreover, NPI-0052 is orally
      bioactive. In animal tumor model studies, NPI-0052 is well tolerated and prolongs
      survival, with significantly reduced tumor recurrence. Combining NPI-0052 and
      Bortezomib induces synergistic anti-MM activity. Our study therefore provides the
      rationale for clinical protocols evaluating NPI-0052, alone and together with
      Bortezomib, to improve patient outcome in MM.

PMID- 16286250
TI  - Current advances in xenotransplantation.
AB  - BACKGROUND: Transplantation of organs is a well-known and accepted life-saving
      procedure for end-stage kidney, liver, heart and lung diseases. The insufficient
      number of donor organs limits the application of this technique and leads to
      unnecessary loss of life. Experimental techniques such as xenotransplantation are
      extremely important to determine new methods of creating organ availability. DATA
      SOURCES: A literature search of Pubmed database was conducted and research
      articles reviewed. RESULTS: Xenotransplantation is a progressive field of
      research. Human complement regulatory protein (hDAF) transgenic pigs and new
      immunosuppressive strategies that reduce xenoreactive alphagal antibodies, have
      decreased rates of acute vascular rejection. Transplantation of alpha-1, 3
      galactosyltransferase knock-out pig organs into baboons has resulted in the
      longest graft survival to date. Coagulation pathways have been identified as
      having a role in graft rejection. In vitro studies of porcine endogenous
      retroviruses (PERVs) show encouraging results that zoonosis will be less
      hindering to xenotransplantation than once thought. CONCLUSIONS: Several recent
      advances in xenotransplantation research have brought this technique closer to
      clinical application. The Ethics Committee of the International
      Xenotransplantation Association has made recommendations to ensure maintenance of
      ethical standards.Advancement will depend on the development of pig models, novel
      immunosuppressive strategies to target the innate immune system, and new ways to
      create donor specific tolerance. Prevention of rejection and transmission of
      infectious agents remain unresolved issues. In the future, it is feasible that
      xenotransplantation will be used to resolve this medical dilemma.

PMID- 16286249
TI  - Dystrophin glycoprotein complex dysfunction: a regulatory link between muscular
      dystrophy and cancer cachexia.
AB  - Cachexia contributes to nearly a third of all cancer deaths, yet the mechanisms
      underlying skeletal muscle wasting in this syndrome remain poorly defined. We
      report that tumor-induced alterations in the muscular dystrophy-associated
      dystrophin glycoprotein complex (DGC) represent a key early event in cachexia.
      Muscles from tumor-bearing mice exhibited membrane abnormalities accompanied by
      reduced levels of dystrophin and increased glycosylation on DGC proteins. Wasting
      was accentuated in tumor mdx mice lacking a DGC but spared in dystrophin
      transgenic mice that blocked induction of muscle E3 ubiquitin ligases.
      Furthermore, DGC deregulation correlated positively with cachexia in patients
      with gastrointestinal cancers. Based on these results, we propose that, similar
      to muscular dystrophy, DGC dysfunction plays a critical role in cancer-induced
      wasting.

PMID- 16286251
TI  - Ischemic cholangiopathy after liver transplantation.
AB  - Orthotopic liver transplantation (OLT) has evolved over the last forty years from
      an experimental endeavor to standard of care therapy for many patients with end
      stage hepatic disease. Many technical advances have contributed to the current
      success of OLT, but surgical complications, especially involving the biliary
      reconstruction, remain a morbid problem. Biliary complications after OLT include
      leaks and strictures. Strictures may be anastomotic or intrahepatic and diffuse,
      as seen in cases of hepatic artery thrombosis. Current efforts to expand the
      limited donor pool include the use of non-heart beating donors. The organ
      procurement process in these donors entails an increased period of warm ischemia
      and results with non-heart beating donor grafts have been mixed. It is now
      appreciated that there is an increased incidence of subsequent diffuse biliary
      stricturing or "ischemic cholangiopathy" in recipients of these organs. Animal
      models of this phenomenon and potential therapeutic strategies targeted at
      ischemic cholangiopathy are being developed with potential applicability to non
      heart beating donation and will be the focus of this review.

PMID- 16286252
TI  - Hepatitis B virus reinfection after liver transplantation: related risk factors
      and perspective.
AB  - BACKGROUND: In recent years, liver transplantation (LT) has been acknowledged as
      an acceptable option for patients with hepatitis B virus (HBV) related end-stage
      liver diseases. However, HBV reinfection is an important event affecting the long
      term survival of recipients. This paper was to review the risk factors related to
      HBV reinfection after LT. DATA SOURCES: English literature was reviewed based on
      MEDLINE focusing on the potential factors related to HBV reinfection after LT.
      RESULTS: HBV reinfection attributes to the unfavorable prognosis after LT. Many
      related factors may be responsible for it, including recipent factors (ethnical
      background, preoperative HBV replication status, extrahepatic HBV existence
      status), donor factors (compromised donor liver, HLA-A, -B compatibilities),
      perioperative treatment (use of antiviral agents, drug resistance, virus
      mutation, immunosuppressants protocol, blood transfusion) and others.
      CONCLUSIONS: The successful management of HBV reinfection will only be achieved
      by perfect clarification of its mechanism. The new strategies include new
      antiviral agents, gene therapy and immune intervention, reliable use of the
      compromised donor livers, and so on.

PMID- 16286253
TI  - Advances in prophylaxis and treatment of recurrent hepatitis B after liver
      transplantation.
AB  - BACKGROUND: In the 1990s, liver transplantation for hepatitis B virus (HBV)
      related-liver diseases was a very controversial issue because the graft was
      inevitably recurrent after liver transplantation. Significant progress has been
      made in the prophylaxis and treatment of recurrent hepatitis B after liver
      transplantation. This review covers the mechanisms, prophylaxis, and treatment of
      hepatitis B recurrent after liver transplantation. DATA SOURCES: Searching
      MEDLINE (1995-2004) for articles on liver transplantation. RESULTS: HBV
      reinfection after liver transplantation results from HBV particles in circulation
      or other extrahepatic sites. Hepatitis B immune globulin (HBIG) was effective in
      reducing HBV reinfection and improving graft survival after liver
      transplantation. Lamivudine has also dramatically reduced the recurrence of HBV
      in the patient undergoing liver transplantation. CONCLUSIONS: Combination HBIG
      and lamivudine is the most effective porphylatic regimen. Lamivudine and adefovir
      are highly effective in treatment of HBV recurrence. HBV-related liver disease is
      no longer a contraindication for liver transplantation.

PMID- 16286254
TI  - Portal vein thrombosis.
AB  - BACKGROUND: Most physicians in China may neglect portal vein thrombosis (PVT) in
      clinical practice. In fact, portal vein thrombosis is an important cause of non
      cirrhotic portal hypertension. As the diversity of its clinical manifestations,
      misdiagnosis is common if we donot bear PVT in mind during differential
      diagnosis. Therefore, we systematically reviewed PVT in terms of etiology,
      pathophysiology, pathology, clinical manifestations, and management. DATA
      SOURCES: An English language literature search (from 1980 to 2004) was performed
      using Medline and Medscape, and articles closely related to PVT were selected.
      RESULTS: PVT is the second cause of portal hypertension after liver cirrhosis in
      western countries. Liver cirrhosis and hepatocellular carcinoma, intra-abdominal
      infection, thrombophilic disorders including myeloproliferative diseases are
      strongly associated with the development of PVT. Liver transplantation is an
      emerging etiological factor of PVT with the development and wide use of this
      technique. Gastrointestinal bleeding resulted from esophageal varices, abdominal
      pain, splenomegaly and hypersplenism and ascites are common manifestations of
      PVT. However there are differences in etiological and clinical presentations
      between children and adults. Diagnosis of PVT depends on imaging studies
      including Doppler ultrasonography, computed tomography (CT), magnetic resonance
      imaging (MRI), and portography. Endoscopic therapy is recommended for variceal
      bleeding in PVT. Anticoagulant treatment for acute PVT is widely accepted in
      western countries. CONCLUSIONS: PVT may be unrecognized as the clinical
      manifestations are unspecific. Misdiagnosis and delayed treatment can lead to
      poor prognosis. Systematical collection of epidemiological and clinical data
      about PVT is necessary in China.

PMID- 16286255
TI  - Liver regeneration after split liver transplantation.
AB  - BACKGROUND: The number of split liver transplantations (SLT) has increased in the
      last 5 years. Regeneration after the loss of hepatic tissue is a fundamental
      response to liver injury. Because partial-liver grafts may not be an optimal size
      for recipients,the purpose of this study was to investigate the regeneration of
      graft liver after SLT. METHODS: Four recipients have undergone SLT at our
      hospital since 2002. The graft liver volume (GLV) in the postoperative day (POD)
      was measured by computed tomography (CT) and the serum levels of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB),
      prealbumin (PA) and albumin (ALB) were monitored. The GLV at different
      postoperative times was compared to the recipient's standard liver volume (SLV)
      and the liver volume regeneration ratio (LVRR) was calculated. In order to
      compare SLV in recipient 2, we measured the total liver volume including the
      graft and the residual native liver as the GLV. RESULTS: The GLV/SLV at POD120
      and POD360 of recipient 1 was measured 114% (1159.32 cm(3)/1016.95 cm(3)), 97%
      (986.44 cm(3)/1016.95 cm(3)) with the LVRR being -11.0%, -24.3%, respectively.
      For recipient 2, it was measured 96% (927.32 cm(3)/965.96 cm(3)) and 100% (968.98
      cm(3)/965.96 cm(3)), with the LVRR being 24.4%, 30.0%, respectively. The initial
      graft volume of segment II, III was 265.36 cm(3) and increased to 335.24 cm(3)
      and 360.56 cm(3) at POD120 and POD360, respectively, with the LVRR being 26.3%
      and 35.9%, respectively. The GLV/SLV at POD60 of recipient 3 was 86% (893.04
      cm(3)/1038.42 cm(3)) and the LVRR was 12.0%. For recipient 4, it was 90% (567.48
      cm(3)/630.54 cm(3)) whereas the LVRR was 20.0%. The serum levels of ALT, AST and
      TB in all recipients declined gradually and returned to normal while the serum
      levels of PA and ALB increased to normal. The serum levels of ALT and AST peaked
      within 3 days after SLT. The neurological symptoms of Wilson's disease in
      recipient 2 were improved markedly. The levels of serum copper and copper-protein
      decreased to 30 mg/L, 120 mg/L at POD120 and the Kayser-Fleischer rings began to
      obliterate. CONCLUSIONS: The size of the transplanted liver after SLT tends to
      converge to the standard liver volume with time and it is adequate clinically for
      SLT to meet the need of the body's metabolic demands. The functional recovery of
      the graft liver occurs earlier than the morphological restoration.

PMID- 16286256
TI  - Effect of small intestinal submucosa on islet recovery and function in vitro
      culture.
AB  - BACKGROUND: The ability to maintain isolated human islet preparation in tissue
      culture has recently been adopted by most islet transplant centers to improve the
      safety and practicality of islet transplantation. However, maintaining islet
      viability and recovery remains a challenge in clinical setting. Extracellular
      matrix (ECM) is one of the most important components of islet microenvironment.
      The reconstruction of the cell-matrix relationship seems to be effective in
      improving the loss of differentiated islet structure and function. Small
      intestinal submucosa (SIS), a naturally occurring ECM, has been investigated to
      be able to promote wound healing, tissue remodeling, and cell growth. The purpose
      of this study was to evaluate the recovery and function of isolated rat
      pancreatic islets after in vitro culture with SIS. METHODS: Pancreatic islets
      were isolated from Wistar rats by using standard surgical procurement followed by
      intraductal collagenase distension, mechanical dissociation, and EuroFicoll
      purification. Groups of purified islets were cultured in plates which were coated
      with multilayer SIS (SIS-treated group) or without (standard cultured group) for
      7 days and 14 days in standard islet culture conditions of RPMI 1640 tissue
      culture media in humidified atmosphere containing 95% air and 5% CO2 at 37 degree
      centigrade. The mean recovery of islets after the culture period was determined
      by sizing duplicate counts of a known volume and their viability was assessed by
      static incubation with low glucose (2.7 mmol), high glucose (16.7 mmol) and high
      glucose solution supplemented with 50 mum 3-isobutyl-1-methylxanthine (IBMX)
      solution. RESULTS: After 7 days and 14 days of in vitro tissue culture, the SIS
      treated group showed a significantly higher recovery compared with those cultured
      under standard conditions. The recovery in the SIS-treated group was about two
      times of the control group cultured in standard conditions after 14 days culture.
      In the SIS-treated group, there was no statistically difference between the short
      and long periods of culture(95.8+/-1.0% vs. 90.8+/-1.5%, P>0.05). During
      incubation in high glucose (16.7 mmol) solution, there was a 2-3 fold increase in
      insulin secretion from both groups,but the SIS-treated group showed a higher
      increase than the standard cultured group after 14-day culture (20.7+/-1.1 mU/L
      vs. 11.8+/-1.1 mU/L, P<0.05). When islets were placed in the high glucose
      solution supplemented with IBMX, the stimulated insulin response in the SIS
      treated group was higher than that in the standard cultured group in spite of the
      duration of the culture. The stimulation index of the SIS-treated group was about
      2-3 times of the standard cultured group. In addition, after a long period of
      culture, the stimulation index of the SIS-treated group was statistically
      equivalent with that of the short period of culture (9.5+/-0.2 vs. 10.2+/-1.2,
      P>0.05). CONCLUSIONS: The co-culture of isolated rat islets with native sheet
      like SIS can provide an excellent extracellular matrix, possible biotrophic and
      growth factors that promote the recovery and subsequent function of islets after
      in vitro tissue culture. In view of results of this study and rapid degradation
      of SIS in vitro, future studies will investigate the extended duration of culture
      and the effect of SIS on islets in vitro.

PMID- 16286257
TI  - Gene heterogeneity of hepatitis B virus isolates from patients with severe
      hepatitis B.
AB  - BACKGROUND: The pathogenesis of severe hepatitis B remains unknown. Reports have
      indicated that hepatitis B virus (HBV) mutations are important factors in the
      pathogenesis of this disease. This study was to investigate the genetic
      heterogeneity of HBV strains from serum samples of patients with fulminant
      hepatitis B. METHODS: Full-length HBV genomes from 4 patients with severe
      hepatitis B were cloned and sequenced to observe mutations in every open reading
      frame (ORF). Serum samples of another 25 patients with severe hepatitis B, 30
      patients with chronic hepatitis B, and 25 HBV carriers were collected for
      sequencing and comparison of mutations in preS2, preC and core promoter regions.
      RESULTS: Of 4 HBV full-length genome sequences, 3 had a G to A mutation at
      nucleotide A1896 in the preC region and 1 had double mutations of T1762-A1764 in
      the core promoter region. The 4 sequences showed mutations in the known B or T
      cell epitopes of the preS2 and C regions. For the other 3 groups, more mutations
      were seen in the preS2 region in the HBV isolates from the patients with severe
      hepatitis B than those from the patients with chronic hepatitis B and HBV
      carriers (P<0.01). There was a significant difference of mutations in the T cell
      epitope region of preS2 between the patients with severe hepatitis B and those
      with chronic hepatitis B or HBV carriers (P<0.01). In the preC and core promoter
      regions, the mutation frequencies of T1653 and C1753 were 48.0% and 24.0%
      respectively in the patients with severe hepatitis B, but none of these mutations
      were observed in the patients with chronic hepatitis B group or HBV carriers
      (P<0.01). The mutation frequency of T1762-A1764 was 76.0% in the patients with
      severe hepatitis B, 40.0% in the patients with chronic hepatitis B (P<0.01), and
      16.0% in the HBV carriers (P<0.01). There was a significant difference in A1896
      mutation between the patients with severe hepatitis B and the patients with
      chronic hepatitis B (P<0.05) or the HBV carriers (P<0.05). CONCLUSION: Our
      observations suggest that the accumulation and persistence of high frequency
      mutations or complex mutations may be associated with the development and
      deterioration of HBV infection.

PMID- 16286258
TI  - HBV genotype characterization and distribution in patients with HBV-related liver
      diseases in Zhejiang Province, P.R. China: possible association of co-infection
      with disease prevalence and severity.
AB  - BACKGROUND: There are 8 well-documented genotypes of hepatitis B virus (HBV) at
      this time point. Genotyping can be accomplished based on a partial sequence of
      hepatitis B virus (HBV) genome such as the pre-S or S gene. Several methods have
      been developed and used for HBV genotyping including direct sequencing,
      restriction fragment length polymorphism, line probe assay and enzyme-linked
      immunoassay. Recently, a novel, rapid and cost-effective genotyping method based
      on PCR amplification assay using type-specific primers that can identify all six
      major genotypes has been developed. This study was undertaken to characterise HBV
      genotypes and investigate the association between the prevalence of different
      genotypes and the severity of HBV-induced liver diseases. METHODS: Serum samples
      from carriers of HBV and patients with HBV-related liver diseases from Zhejiang
      Province were screened for viral serological markers using commercially available
      radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA) kits. Serum
      HBV DNA load was determined by real-time detection PCR. A type-specific primer
      based the nested-PCR method was employed in the HBV genotyping. The genotype
      results obtained were confirmed by direct sequencing of nested PCR amplicons of
      the pre-S region. Ten samples of each genotype (B and C) were sequenced. RESULTS:
      The survey on a cohort of 125 HBV carriers in and around Hangzhou City, Zhejiang
      Province showed the existence of HBV genotypes A (0.8%), B (48%), C (40.8%), D
      (0.8%), mixed B and C (9.6%) and an absence of E and F genotypes. Distribution of
      HBV genotypes in patients with liver diseases revealed a statistically
      insignificant higher prevalence of genotype B in mild chronic hepatitis (CH).
      Among the three genotypes B, C and mixed B/C infections 11 (73.3%), 3 (20%) and 1
      (6.7%), (P<0.05), respectively in subjects with moderate CH, genotype B was
      significantly predominant. The infection patterns for genotypes B, C and B/C
      mixed in (i) liver cirrhosis (LC) 4 (23.5%), 10 (58.8%) and 3 (17.7%) and (ii)
      hepatocellular carcinoma (HCC) 2 (28.6%), 5 (71.4%) and 0 (0.0%) respectively
      revealed a marked association of C genotype with liver disease; however, the
      association was statistically insignificant (P>0.05). Differences in positive
      rate of HBeAg for the three genotypes B, 16 (30.8%), C, 27 (51.9%), and mixed
      B/C, 9 (17.3%) were significant (P<0.05), with genotype C showing predominance.
      CONCLUSIONS: These findings show an interesting distribution of HBV A-D genotypes
      in Zhejiang Province. Furthermore, our results indicate a novel and markedly high
      prevalence of mixed B/C genotype infections in subjects with severe CH and LC,
      and a possible association of mixed B/C infections with the severity of liver
      diseases in this region of Mainland China.

PMID- 16286260
TI  - Clearance of HCV RNA in peripheral blood mononuclear cell as a predictor of
      response to antiviral therapy in patients with chronic hepatitis C.
AB  - BACKGROUND: The resolution of hepatitis C, evidenced by normalization of liver
      function and disappearance of hepatitis C virus RNA from serum as determined by
      conventional laboratory assays, reflects virus eradication. But in interferon
      treated patients the HCV RNA in serum sometimes could not show the virus in
      cells. Such factors as virus genotype, HCV RNA contents in serum, HCV specific
      cellular immunities after treatment were reported to predict the response to
      interferon therapy. In most patients, HCV RNA could detect the virus in
      peripheral blood mononuclear cell. The aim of this study was to investigate the
      predictive value of HCV RNA in PBMC of patients with chronic hepatitis C after
      interferon treatment. METHODS: Sixteen patients with chronic hepatitis C were
      treated with interferon for 24 weeks, and they all get complete responses at 12
      weeks of treatment. At the end of treatment, the HCV RNA in PBMC and serum were
      detected by RT-PCR, and after stopping treatment, HCV RNA in serum was monitored
      continually. RESULTS: In 9 patients who were HCV RNA positive in their PBMC at
      the end of treatment, 8 showed serum HCV RNA positive after 24 weeks and another
      1 after 1 year. In 7 patients with negative HCV RNA in their PBMC, only 2
      patients relapsed in serum HCV RNA after 1-year follow-up, and others remained
      viral response after 3.5 years. CONCLUSION: HCV RNA in PBMC at the end of IFN
      treatment is a predictor of durable response to antiviral therapy in patients
      with chronic hepatitis C.

PMID- 16286259
TI  - Abnormal expression of hepatomas and circulating telomerase and its clinical
      values.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant
      tumours worldwide. Telomerase is reactivated in various types of malignant tumors
      and may contribute to the development of HCC. To evaluate the role of telomerase
      in formation and development of HCC, we analyzed its expression status in
      different parts of HCC tissues and peripheral blood mononuclear cells (PBMCs),
      and explored its clinical implications for diagnosis of HCC. METHODS: Total RNAs
      and telomerase were extracted from HCC and their non-cancerous tissues, and both
      relationships were analyzed between them. The expression of telomerase reverse
      transcriptase (hTERT) mRNA and telomerase activities in liver tissues and PBMCs
      were detected by RT-PCR and telomeric repeat amplification protocol (TRAP)-ELISA,
      respectively. The diagnostic values of telomerase in PBMCs were investigated in
      the diagnosis and differentiation of HCC. RESULTS: The specific activities of
      telomerase were 18.25+/-15.02 A/microg RNA in HCC tissues, and significantly
      higher than those in their non-cancerous tissues (8.16+/-6.22 A/microg RNA,
      P<0.05). But total RNA levels in HCC were 12.40+/-7.34 microg/mg wet liver and
      lower than 53.77+/-52.02 microg/mg wet liver in their non-cancerous parts
      (P<0.01). The different telomerase levels could be detected in PBMCs from
      patients with chronic liver diseases and control group. The enzyme activities
      were significantly higher in HCC than in any other groups (P<0.01). However,
      circulating telomerase levels were more obviously decreased in HCC patients after
      transcatheter arterial embolization treatment than before the treatment (P<0.01).
      The analysis of combined serum alpha-fetoprotein level and PBMCs telomerase was
      more sensitive and specific for the diagnosis of HCC. CONCLUSION: The abnormal
      expression of telomerase in HCC tissues and circulating PBMCs could be a useful
      marker to the diagnosis and prognosis of HCC.

PMID- 16286261
TI  - Cryoablation of malignant liver tumors: results of a single center study.
AB  - BACKGROUND: Local ablative procedures such as cryosurgery and thermo-ablation are
      increasingly employed as a supplement to liver resection for the therapy of
      primary and secondary liver tumors. It is still unclear if the survival time can
      be extended through local ablative procedures. This prospective study shows
      operative actions, complications and long-term follow-up of 19 patients
      undergoing cryotherapy. METHODS: Between 1997 and 1998, 19 patients underwent
      cryotherapy due to a non-resectable malignant liver tumor (17 patients with
      metastases of a colon carcinoma, 2 patients with a hepatocellular carcinoma).
      Twelve patients (63.2%) received cryotherapy only and seven patients (36.8%)
      received a combination of resection and cryotherapy. The median follow-up period
      was 23 months. RESULTS: In a total of 59 liver tumors (18 were resected and 41
      received cryotherapy), 12 had cryotherapy only, and 7 had a combination of
      cryotherapy and resection. The 30-day lethality was 0%, and the rate of major
      complications was 21%. After one year, 27.3% of the patients were still
      recurrence-free. The recurrence rate for all tumors treated was 58.8%. The median
      survival time for all patients was 21 months. The one- and three-year survival
      rates were 62.5% and 15.8%, respectively. CONCLUSIONS: The mortality for
      cryotherapy is low, but there is a high rate of complications and long-term tumor
      control is not sufficient. If local ablative procedures of hepatic lesions are to
      be performed, not laparotomy but percutaneous, percutaneous thermoablation should
      be discussed as an alternative therapeutic measure.

PMID- 16286262
TI  - The Chinese classification system compared with TNM staging in prognosis of
      patients with primary hepatic carcinoma after resection.
AB  - BACKGROUND: The life expectancy of a patient with primary hepatic carcinoma (PHC)
      is hard to predict, and it is related to many prognostic factors. The Chinese
      classification system including five parameters: tumor, vascular thrombosis,
      lymph node metastasis, distant metastasis and Child-Pugh stage developed in 1999
      was adopted by the 8th National Conference on Liver Cancer of the Chinese Anti
      Cancer Association in 2001. In this study, the discriminatory ability of the
      Chinese classification system was compared with that of the TNM staging in
      patients for resection of PHC, in addition to the evaluation of prognostic value.
      METHODS: The data of 246 patients who had undergone resection of PHC from January
      1986 to December 2000 (average age, 51 years; male/female ratio, 213/33) were
      retrospectively studied. Among the 246 patients, 227 were followed up for at
      least 3 years. RESULTS: The 1-, 3-, 5-, 7-, and 10-year tumor-free survival rates
      were 55%, 30%, 25%, 20% and 18%, respectively. The Chinese classification system
      was better than the TNM staging system in predicting survival rate of patients
      with PHC, as confirmed by survival curves shown by the Kaplain-Meier method. The
      mean survival time was 155, 70, 39, 16, and 4 months in patients with the Chinese
      classification stages Ia, Ib, IIa, IIb, and III, respectively. The 1-, 3-, 5-, 7
      , and 10-year tumor-free survival rates of the Chinese classification system and
      TNM staging were statistically significant and had a slightly positive
      relationship. The predictive capacity of the Chinese classification system was
      confirmed in any two subgroups of patients undergoing operation. COX proportional
      hazards regression analysis showed that the Chinese classification system was the
      only independent prognostic factor for survival. CONCLUSIONS: Taking both tumor
      extension and liver function into account, we consider that the Chinese
      classification system making up for the deficiency of UICC TNM staging is more
      precise in predicting the prognosis of patients with resection of PHC.

PMID- 16286263
TI  - Hepatic segmentectomy for treatment of hepatic tuberculous pseudotumor.
AB  - BACKGROUND: This study was designed to explore the preoperative diagnosis and
      surgical modality of patients with hepatic tuberculous pseudotumor. METHODS: Of
      682 patients who had undergone liver resection from January 1988 to December
      2004, 8 were confirmed pathologically as having hepatic tuberculous pseudotumor
      after operation. Their clinical features, laboratory findings,results of
      preoperative imaging and surgical modality of the 8 patients were analyzed.
      RESULTS: In these patients, 5 were misinterpreted as having other types of liver
      tumor and 3 were confirmed as having liver tuberculous pseudotumor
      preoperatively. All the 8 patients underwent hepatic segmentectomy and local
      hepatic resection. Seven had no tumor recurrence after follow-up for 4 years.
      CONCLUSIONS: Hepatic tuberculous pseudotumor was highly suspected for the
      patients with hepatic occupying-space lesions who had a history of tuberculosis.
      Fine needle aspiration liver biopsy guided by B-mode ultrasound and CT scan could
      confirm the diagnosis. They are of vital importance in the pathological diagnosis
      of the tumor. Therapeutic modalities included all kinds of hepatic segmentectomy
      and postoperative administration of antituberculous agents for the enhancement of
      the therapeutic effects.

PMID- 16286264
TI  - Expression pattern of matrix metalloproteinases-13 in a rat model of alcoholic
      liver fibrosis.
AB  - BACKGROUND: Interstitial collagenase has been considered as an essential enzyme
      for collagenolysis in liver fibrosis, because type I and III collagens increase
      predominantly in liver fibrosis. The present study aimed to demonstrate the gene
      expression of matrix metalloproteinases-13 (MMP-13) in the progressive phases of
      ethanol induced experimental liver fibrosis in rats. METHODS: Thirty-four Sprague
      Dawley rats were randomly divided into two groups. The experimental group (24
      rats) was given ethanol (44%, 7 g/kg) every day and the control group (10) was
      given normal saline. Liver samples were harvested from experimental rats at 4, 12
      and 24 weeks respectively. The kinetics of MMP-13 mRNA expression was assayed by
      semi-quantity reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS:
      In normal rat liver, a faint band for MMP-13 mRNA was observed by RT-PCR (0.24+/
      0.41). The gene expression of MMP-13 was increased in the liver of the rats
      treated with ethanol for 4 weeks (0.62+/-0.54), but it was not considered
      statistically significant (P>0.05). And the livers from 12-week-treated rats
      showed a marked mRNA expression (1.65+/-0.47, P<0.01). Once fibrosis became
      prominent (24 weeks), a faint band of MMP-13 mRNA was observed (0.39+/-0.25).
      CONCLUSION: MMP-13 participates in the degradation of newly-formed matrix in the
      early phase of rat liver fibrosis induced by ethanol, and it was induced in a
      distinct time frame.

PMID- 16286265
TI  - In vitro cleavage of hepatitis B virus C mRNA by 10-23 DNA enzyme.
AB  - BACKGROUND: 10-23 DNA enzyme is one kind of deoxyribozymes for RNA cleavage. The
      inhibition effects of 10-23 DNA enzyme on the expression of the HBV C gene in
      HepG2.2.15 cells were demonstrated previously. The aim of this study was to
      further explore the cleavage activities of 10-23 DNA enzyme targeting at HBV C
      gene mRNA in vitro. METHODS: 10-23 DNA enzyme named Drz-HBV-C-9 specific to HBV C
      gene ORF A(1816)UG was designed and synthesized. HBV C gene mRNA was obtained by
      the in vitro transcription method. Cleavage activities of Drz-HBV-C-9 were
      observed in vitro. Values of kinetic parameters including Km,Kcat and Kcat/Km
      were calculated accordingly. RESULTS: Under the certain cleavage conditions, Drz
      HBV-C-9 could efficiently cleave target mRNA at specific sites in vitro. Cleavage
      products of 109nt plus 191nt were obtained. The kinetic parameters, Km, Kcat and
      Kcat/Km for Drz-HBV-C-9, were 1.4 X 10(-9) mol, 1.6 min-1 and 1.1 X 10(9) mol(-1)
      x min(-1), respectively. CONCLUSIONS: 10-23 DNA enzyme targeting at HBV C gene
      mRNA possesses specific cleavage activities in vitro. This would be a potent
      antiviral strategy with respect to HBV gene therapy.

PMID- 16286267
TI  - Fabrication and data harvesting of casting sample of rat liver blood vessels.
AB  - BACKGROUND: The configuration and course of liver blood vessels (LBVs) are
      involved in the study of pathogenesis of hepatic diseases including liver
      cirrhosis, tissue engineering of the liver and surgical treatment of diseases of
      the liver and gallbladder. In the study of vascularization in tissue engineering
      of the liver in particular, the work we should do is to get the anatomy data of
      LBVs for computer-aided reconstruction of digital model of LBVs. In doing so, the
      casting sample of rat liver blood vessels (RLBVs) is fabricated and the data of
      each section of the sample is harvested. METHODS: Liquid polymer preparation (8%
      10%), which was made of chlorinated poly vinyl chloride (CPVC) as a solute,
      acetone as solvent and pigment, was injected into the RLBVs of 40 rats. Once
      acetone evaporated, the preparation solidified. When the cells and connective
      tissue were dissolved by hydrochloric acid, a casting sample of RLBV was left.
      The sample was embedded in paraffin and cut into sections. The data of each
      section of RLBVs was collected by digital camera. RESULTS: In 36 rats, the
      casting sample of RLBVs was made successfully by this method. The diameter of the
      hepatic arteries varied from 0.8 to 0.2 mm, the portal veins from 2.0 to 0.1 mm,
      and the hepatic veins from 2.2 to 0.2 mm. In each rat, about 150 photographs of
      the sections of RLBVs were taken. CONCLUSION: The method described above is
      feasible for getting experimental data for computer-aided reconstruction of the
      digital model of RLBVs.

PMID- 16286266
TI  - Hepatic injury in rats with obstructive jaundice: roles of the protein kinase C
      signal pathway and cytoprotection of fructose.
AB  - BACKGROUND: Fructose is cytoprotective during bile salt-induced apoptosis of
      hepatocytes by regulating protein kinase C (PKC). This study was undertaken to
      explore the regulating mechanism of hepatic injury in rats with obstructive
      jaundice, and to detect the PKC signal pathway. METHODS: Rat hepatocytes were
      isolated by in situ collagenase perfusion and primary culture, and pretreated
      with various concentrations of PKC agonist phorbol myristate acetale (PMA) and
      inhibitor chelerythrine for 20 minutes. After pretreatment, 50 mumol/L
      glycochenodeoxycholate (GCDC) was added for additional 24 hours. Subsequently,
      the cells were detected by FCM and TUNEL. After adding with different
      concentrations of fructose and 100 mumol GCDC, the hepatocytes were evaluated by
      FCM and TUNEL. Experimental obstructive jaundice was induced with fructose and
      without fructose via double ligation of the bile duct for 3, 7, 14, and 21 days.
      Apoptotic status in the liver of all rats was detected with TUNEL, and PKC
      protein in the liver of obstructive jaundice (OJ) with the immunohistochemistry
      method. RESULTS: PMA increased GCDC-induced apoptosis and chelerythrine decreased
      GCDC-induced apoptosis in a concentration-dependent manner. Adding with different
      concentration of fructose and 100 mumol GCDC, the decreased apoptotic rate was
      related to the concentration of fructose. The apoptotic rate of the liver was
      related to times of OJ. PKC and apoptosis index (AI) were the highest after a 14
      day ligation of the bile duct without use of fructose. AI and PKC were decreasing
      from a 14-day ligation of the bile duct with fructose. CONCLUSIONS: PKC takes
      part in the regulation, occurrence, and progression of hepatic injury in OJ.
      Fructose is cytoprotective during bile salt-induced apoptosis of hepatocytes by
      regulating PKC.

PMID- 16286268
TI  - An analysis of 680 cases of cholangiocarcinoma from 8 hospitals.
AB  - BACKGROUND: The outcome of patients with cholangiocarcinoma is poor. To evaluate
      the experience in the diagnosis and surgical treatment of cholangiocarcinoma, we
      investigated the status quo of diagnosis and treatment of cholangiocarcinoma in
      China. METHOD: The clinical data of 680 patients with cholangiocarcinoma treated
      at 8 hospitals from 1995 to 2001 were retrospectively analyzed with SPSS software
      package. RESULTS: The incidence of the tumor was the highest in the age group of
      60-65 years. Meanwhile, the incidence was higher in aged men than in aged women,
      with a male to female ratio of 1.39:1. Proximal cholangiocarcinoma was the
      commonest (41.6%) and distant cholangiocarcinoma the second (28.7%) in the 680
      patients. B-mode ultrasonography for cholangiocarcinoma was performed in 80.3% of
      the patients. Non-traumatic examinations such as computed tomography (CT),
      magnetic resonance image (MRI) and magnetic resonance cholangiopancreatography
      (MRCP) were more widely used than that of traumatic examinations such as
      percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde
      cholangiopancreatography (ERCP). The low- and middle-differentiation cancer of
      the proximal bile duct accounted for about 50%. Most of the patients suffered
      from late-stage cholangiocarcinoma. The resection rate of the tumor was low, and
      the rate of radical operation was only 21.6% (147/680). CONCLUSIONS:
      Cholangiocarcinoma is common in the aged men. Its diagnosis and treatment have
      been improved, but little. Most patients are diagnosed as having late-stage
      cholangiocarcinoma at the time of outpatient clinic, and the rate of radical
      operation is low. Therefore, it is necessary to reinforce the early diagnosis and
      treatment of cholangiocarcinoma to improve the outcome after operation.

PMID- 16286269
TI  - Surgical treatment for Nevin stage IV and V gallbladder carcinoma: report of 70
      cases.
AB  - BACKGROUND: The role of aggressive surgery for end-stage gallbladder carcinoma is
      controversial. This retrospective study was designed to evaluate the outcome of
      surgical treatment for Nevin stage IV and V gallbladder carcinoma at a single
      institution. METHODS: A retrospective analysis was made on 70 patients with Nevin
      stage IV and V gallbladder carcinoma undergoing surgical treatment from January
      1993 to June 2004. RESULTS: There were 22 cases of stage IV and 48 of stage V.
      Cholecystectomy was performed in 37 cases with a resection rate of 53%, 9 cases
      received radical resection, 13 extended radical resection, and 15 palliative
      resection. The curative resection rate was 31% and the morbidity rate was 36%.
      Postoperative 1-, 3-, 5-year survival rates of curative and palliative resection
      were 69%, 33%, 8% and 27%, 13%, 0, respectively (P<0.01). The 1- and 3-year
      survival rates of patients undergoing exploratory laparotomy only were 3% and 0,
      respectively. CONCLUSIONS: Nevin stage IV and V gallbladder carcinoma should be
      treated by aggressive surgery. Curative resection is promising in the improvement
      of long-term survival rate.

PMID- 16286270
TI  - Oral (99m)Tc-DTPA simultaneous determination of duodenobiliary reflux and
      intestinal permeability in patients after choledocholithotomy plus T-tube
      drainage.
AB  - BACKGROUND: The high choledocholithiasis recurrence rate after
      choledocholithotomy plus T-tube drainage is related to biliary bacterial
      infection. These bacteria are from the intestine, either via the major duodenal
      papilla, or the penetrating intestinal mucosa. It is therefore possible that
      duodenobiliary reflux and increased intestinal permeability exist in patients who
      have undergone choledocholithotomy. This study was undertaken to find the
      evidence of duodenobiliary reflux and to assess intestinal permeability in these
      patients. METHODS: Twenty-one patients who underwent choledocholithotomy plus T
      tube drainage 2 months ago, and 11 healthy volunteers (controls) took orally
      185MBq of (99m)Tc-DTPA. The patients' bile was collected in the next 2 hours via
      a T-tube and the (99m)Tc-DTPA radioactivity in the bile was counted. Intestinal
      permeability was evaluated by measuring the 24-hour urinary excretion rate of
      ingested (99m)Tc-DTPA in both patients and controls. RESULTS: In 6 of the 21
      patients, radioactivity in the bile was detected. The intestinal permeability was
      significantly higher in patients (11.45%+/-6.16%) than that in controls (3.61%+/
      1.63%, t=3.28, P<0.05). CONCLUSIONS: Duodenobiliary reflux exists in patients who
      have undergone choledocholithotomy plus T-tube drainage. The intestinal
      permeability is higher in these patients than in healthy subjects. Duodenobiliary
      reflux and increased intestinal permeability may be factors of cholelithiasis
      recurrence.

PMID- 16286271
TI  - Middle and long-term clinical outcomes of patients with regional hepatolithiasis
      after subcutaneous tunnel and hepatocholangioplasty with utilization of the
      gallbladder.
AB  - BACKGROUND: Roux-en-Y choledochojejunostomy is routinely performed in patients
      with regional hepatolithiasis. However, some of these patients, who have a normal
      gallbladder and normal Oddi's sphincter, are unnecessarily undergoing bilio
      intestinal drainage. Alternatively, reconstruction can be achieved by
      subcutaneous tunnel and hepatocholangioplasty with the utilization of the
      gallbladder (STHG). This method is effective to potential endoscopic tunnel and
      intervention during follow-up, and prevention of reflux cholangitis as well as
      the disorders of the GI tract. METHODS: The middle and long-term complications of
      46 patients who underwent STHG were analyzed. With B-ultrasonography and
      biochemical assay, the contraction and concentration function of the gallbladder
      were also studied. RESULTS: Follow-up showed that all patients survived with a
      relatively normal life. One patient experienced right epigastric pain, chills and
      fever because of a stone which impacted in the left hepatic bile duct. Another
      patient had cholangitis because of biliary ascariasis. The two patients were
      treated by endoscopic therapy within the subcutaneous gallbladder under local
      anesthesia. CONCLUSIONS: This operation not only keeps the normal physical
      functional of the gallbladder, Oddi's sphincter and gastrointestinal tract, but
      also prevents reflux cholangitis and the disorder of the digestive tract. Hence
      STHG is a novel operation dealing with regional hepatolithiasis.

PMID- 16286272
TI  - Lipase and pancreatic amylase activities in diagnosis of acute pancreatitis in
      patients with hyperamylasemia.
AB  - BACKGROUND: Measurement of total serum amylase (AMY) is the most widely used
      biochemical test for the diagnosis of acute pancreatitis, but it is commonly
      considered a nonspecific marker. To improve the biochemical diagnosis of acute
      pancreatitis, lipase (LIP) and pancreatic amylase (PAMY) have been tested in
      recent years. The present study was designed to evaluate whether serum LIP and
      pancreatic PAMY tests could replace total amylase test to improve diagnostic
      efficiency in the evaluation of acute pancreatitis in patients with
      hyperamylasemia. METHODS: LIP and PAMY values were determined in serum samples
      from 92 patients with hyperamylasemia. Reference values for each enzyme were
      derived from serum samples of 147 healthy subjects. The activities of LIP and
      PAMY in patients with various diseases were shown directly by the boxplot graph.
      The diagnostic accuracy of LIP and PAMY was defined as the area under the
      receiver operating characteristic (ROC) curve. Their sensitivity and specificity
      in detecting acute pancreatitis at varying cutoff points were shown by the curve,
      and the best cutoff value for each enzyme was shown by the modified ROC curve.
      The diagnostic values of LIP, PAMY and LIP+AMY with each upper limit of reference
      range (ULR) were compared with the corresponding best cutoff values. RESULTS: The
      references values of LIP and PAMY were 12.2-47.6 U/L and 28-95 U/L, respectively.
      These values in patients with acute pancreatitis were higher than those patients
      with other diseases. The areas under the ROC curve (AUC) of LIP and PAMY were
      0.799 and 0.792, respectively. With the best diagnostic cutoff point of maximum
      (sensitivity + specificity)-100%, we obtained values of 97.9 U/L (LIP(97.9)=2.06
      X ULR) for LIP and 209 U/L (PAMY(209)=2.20 X ULR) for PAMY. The best cutoff
      values for LIP, PAMY and LIP+AMY demonstrated the specificity, positive
      predictive value, and diagnostic efficiency higher than the corresponding ULRs.
      CONCLUSIONS: Serum LIP and PAMY are specific for the pancreas and might replace
      total amylase for the diagnosis of acute pancreatitis in hyperamylasemia
      patients. LIP(97.9) is more efficient than PAMY(209) in the diagnosis of acute
      pancreatitis. A combined test of both enzymes is not superior to single test of
      either enzyme in diagnostic accuracy.

PMID- 16286273
TI  - Protection effect of triptolide to liver injury in rats with severe acute
      pancreatitis.
AB  - BACKGROUND: The high mortality of patients with severe acute pancreatitis (SAP)
      is due to multiorgan dysfunction. The mechanisms of SAP are still obscure. The
      aim of this study was to investigate the role of nuclear factor-kappa B (NF
      kappaB) activation in rats with SAP associated with liver injury and the
      protection effect of triptolide against liver injury in rats with SAP. METHODS:
      Ninety Wistar rats were randomly divided into three groups (n=30 each group):
      severe acute pancreatitis (group P), treatment with triptolide (group T), and
      sham operation (group S). SAP models were induced by retrograde injection of 5%
      sodium taurocholate to the pancreatic duct. After the model was successfully
      established, no treatment was given to group P. In group T, triptolide (0.05
      mg/ml) was injected intraperitoneally (0.2 mg/kg). In group S, the abdominal
      walls of rats were opened, sutured, but not treated. The rats were sacrificed
      after operation at 2, 6, and 12 hours, respectively. The serum levels of amylase
      (AMY), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-6 (IL-6) were determined at three time points (10 rats for each
      time point). Liver tissues were obtained to detect the activity of NF-kappaB and
      to observe their pathological changes with light and electron microscopes.
      RESULTS: The serum levels of AMY and ALT were higher in groups P and T than in
      group S. The serum AMY levels were significantly lower in group T than in group P
      at 12 hours after operation. The serum ALT levels were significantly lower in
      group T than in group P at 6, 12 hours after operation. At the three time points,
      the levels of TNF-alpha and IL-6 in groups P and T increased more significantly
      than in group S. In group T they were decreased more significantly than in group
      P at the three time points. In groups P and T, NF-kappaB activity in liver tissue
      increased more significantly than in group S at the three time points. The
      activity of NF-kappaB was higher in group P than in groups S and T at the three
      time points. Liver pathological damages were milder in group T than in group P
      under light and electron microscopes. CONCLUSIONS: NF-kappaB plays an important
      role in the pathogenesis of liver injury in rats with SAP. Triptolide can reduce
      pathological damage to the liver. Its mechanism is to inhibit the activity of NF
      kappaB and to decrease the release of inflammatory mediators.

PMID- 16286274
TI  - Effect of nitric oxide on toll-like receptor 2 and 4 gene expression in rats with
      acute lung injury complicated by acute hemorrhage necrotizing pancreatitis.
AB  - BACKGROUND: Toll-like receptor (TLR) 2/4 might play important roles in mediating
      proinflammatory cytokine synthesis and release. And nitric oxide (NO) has been
      used to treat acute respiratory distress syndrome (ARDS). This study aimed to
      investigate the changes in TLR2/4 gene expression in the lungs of rats with acute
      lung injury (ALI) complicated by acute hemorrhage necrotizing pancreatitis (AHNP)
      and the effect of NO on the TLR2/4 gene expression. METHODS: One hundred and ten
      SD male rats were randomly divided into sham-operated group (n=10), AHNP group
      (n=30), chloroquine-treated group (n=30), and L-Arg-treated group (n=40). The
      lungs were dissected for lung histological scoring, and bronchoalveolar lavages
      were harvested for lung injury indexing. TLR2/4 mRNA expression in the lungs was
      measured by RT-PCR. RESULTS: TLR2/4mRNA was detected in the lungs with low values
      in the sham-operated group (0.016+/-0.210E-2, 0.112+/-0.750E-2), but it was
      markedly increased at 3 hours in the AHNP group (0.787+/-0.751E-2, 1.512+/-1.794E
      2), peaking at 12 hours (1.113+/-6.141E-2, 2.957+/-2.620E-2; P<0.05 or P<0.01).
      When lung injuries were aggravated, TNF-alpha concentrations in the lungs were
      increased, but NO concentrations were decreased (P<0.05 or P<0.01). When
      TLR2/4mRNA was inhibited by CQ (3h: 0.313+/-5.491E-2, 0.005+/-1.419E-3; 6h:
      0.488+/-7.442E-2, 0.010+/-1.518E-3; 12h: 0.883+/-8.911E-2, 0.024+/-2.760E-3;
      P<0.05 or P<0.01), lung injuries were relieved. NO concentrations in the lungs
      were increased but TNF-alpha concentrations were decreased (P<0.05 or P<0.01).
      When the rats with AHNP were treated with L-Arg, TLR2/4mRNA expression in the
      lungs could be effectively inhibited (50 mg-T: 0.656+/-3.977E-2, 1.501+/-6.111E
      2; 100 mg-T: 0.260+/-0.891E-2, 0.732+/-5.135E-2; 200 mg-T: 0.126+/-0.914E-2,
      0.414+/-1.678E-2; 400 mg-T: 0.091+/-0.399E-2, 0.287+/-0.176E-2;P<0.05 or P<0.01)
      and lung injuries were relieved. At the same time, NO concentrations in the lungs
      were markedly increased, but TNF-alpha concentrations were decreased (P<0.05 or
      P<0.01). CONCLUSIONS: The expression of TLR2/4mRNA is increased in the lungs in
      rats with AHNP and lung injuries are aggravated.TLR2/4mRNA gene expression of the
      lungs of rats with AHNP could be markedly inhibited by NO, leading to the relief
      of lung injuries.

PMID- 16286276
TI  - Versatility and viability of hepatic venoplasty in live donor liver
      transplantation using the right lobe with the middle hepatic vein.
AB  - Including the middle hepatic vein in the right lobe liver graft has the advantage
      of providing direct venous drainage of the right anterior segment. To allow
      unimpeded passage of blood flow, we previously designed venoplasty of the middle
      and right hepatic veins. We found that venoplasty is also feasible when the
      inferior right hepatic vein is near to the right hepatic vein, or when multiple
      segment 8 hepatic vein orifices are exposed adjacent to the middle hepatic vein
      at the graft transection surface. By joining the hepatic vein orifices into a
      single opening, the anastomosis into the inferior vena cava is much facilitated.
      The technique is simple, yet versatile, and able to cope with variation of the
      configurations of the hepatic vein.

PMID- 16286275
TI  - Pathogenesis of acute lung injury in rats with severe acute pancreatitis.
AB  - BACKGROUND: Acute lung injury (ALI) is the most common and severe complication of
      severe acute pancreatitis (SAP). The elucidation of the mechanism of ALI
      contributes to the diagnosis and treatment of the illness. In this study, we
      studied the pathogenesis of ALI in rats with severe acute pancreatitis. METHODS:
      The rats were sacrificed at 1, 3, 5, 6, 9 and 12 hours after the establishment of
      the model of SAP. Pancreas and lung tissues were obtained for pathological study,
      and examination of microvascular permeability and myeloperoxidase (MPO)
      examination. The gene expressions of tumor necrosis factor-alpha (TNF-alpha) and
      intercellular adhesion molecule-1 (ICAM-1) in the pancreas and lung tissues were
      detected by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS:
      After the establishment of the SAP model, the degree of pancreatic and lung
      injury increased gradually along with the gradual increase of MPO activity and
      microvascular permeability. Gene expressions of TNF-alpha and ICAM-1 in the
      pancreas rose at 1 hour and peaked at 7 hours. In contrast, their gene expression
      in the lungs rose slightly at 1 hour and peaked at 9-12 hours. CONCLUSION: An
      obvious time window existed between SAP and lung injury, which is beneficial to
      the early prevention of the development of ALI.

PMID- 16286277
TI  - Pancreatic primary lymphoma: a case report and review of the literature.
AB  - BACKGROUND: Primary pancreatic lymphoma is a rare but treatable malignancy (less
      than 1% of pancreatic tumors) that may be clinically confused with pancreatic
      adenocarcinoma. METHODS: In a patient with upper abdominal pain, ultrasonography
      and CT detected a mass in pancreatic head, which compressed the common bile duct.
      The patient received a Whipple's operation and intraoperative frozen sections of
      the mass showed an anaplastic carcinoma. Immunohistochemical staining was used to
      indicate the origin and prognosis of tumor. RESULTS: Grossly the tumor involved
      the pancreatic head, soft in consistence and invaded part of the gastric wall.
      Histologically, the tumor was composed mainly of large and moderate neoplastic
      cells, which were diffusely positive for CD20 and Bcl-6 antigens, indicating the
      features of diffusely large B cell lymphoma. CONCLUSIONS: The proper diagnosis of
      the tumor should be made with CD20 and Bcl-6 immunohistochemical study. Radical
      surgery is indicated for resectable carcinoma but not for a chemosensitive
      lymphoma.

PMID- 16286278
TI  - Sternal wound complications in bilateral internal thoracic artery grafting: a
      comparison of the off-pump technique and conventional cardiopulmonary bypass.
AB  - BACKGROUND: Sternal wound complication is a major concern in bilateral internal
      thoracic artery grafting. The purpose of this study was to assess whether
      avoiding cardiopulmonary bypass has beneficial effects with fewer wound
      complications in patients receiving bilateral internal thoracic artery grafting.
      METHODS: Retrospective review was performed using prospectively gathered data of
      69 patients who had undergone elective coronary artery bypass grafting and
      received conventional pedicled bilateral internal thoracic artery grafting from
      December 2002 through April 2004 by the same surgical team. The patients were
      divided into 2 groups: those who underwent coronary artery bypass grafting
      without cardiopulmonary bypass (off-pump group, n = 41), and those who underwent
      coronary artery bypass grafting with cardiopulmonary bypass (CPB group, n = 28).
      Chart review and 3-month follow-up were obtained for all patients. These 2 groups
      were compared for sternal wound complications and preoperative, intraoperative,
      and postoperative variables. RESULTS: Deep sternal wound infection (SWI) was seen
      in 1 patient (2.4%), superficial SWI in 2 patients (4.8%), and sternal dehiscence
      in 1 patient (2.4%) in the off-pump group. Deep SWI was seen in no patients,
      superficial SWI in 2 patients (7.1%) and sternal dehiscence in 2 patients (7.1%)
      in the CPB group. No statistically significant difference in the frequency of
      occurrence of sternal complications was detected between the 2 study groups.
      CONCLUSIONS: The results suggest that the avoidance of CPB has no beneficial
      effect on the number of sternal wound complications in patients receiving
      bilateral internal thoracic artery grafting. However, further prospective,
      randomized studies on large patient groups are required to assess this finding.

PMID- 16286280
TI  - Optimized technical and electrophysiological approach for treatment of atrial
      fibrillation.
AB  - The maze procedure initially proposed by Cox for primary atrial fibrillation
      treatment somehow, in its complexity, increases the morbidity risk associated
      with mitral valve surgery. OBJECTIVE: We sought to describe a surgical technique
      that considers the concepts of electrophysiology and to describe the initial
      results of a new surgical and electrophysiological approach that blocks the main
      atrial circuits as defined by Frame, and to optimize the surgical tactic for
      treatment of atrial fibrillation. MATERIAL AND METHODS: Eight patients with
      chronic atrial fibrillation and mitral valve dysfunction, with tricuspid valve
      regurgitation in 1 case, were operated on. The following modifications of the
      classic Cox procedure were employed: (1) exclusion of the left atrium appendage
      with an inner suture that closed the left atrial ostium, (2) exclusion of the
      right atrium appendage by 1 purse-string suture used for fixation of the superior
      vena cava draining cannula, (3) a single atrial incision, (4) transendocardium
      electrocauterization in the left atrium wall around all pulmonary vein ostia, and
      (5) substitution of the incisions and sutures in the left atrium with
      transendocardium electrocauterization. RESULTS: The extracorporeal circulation
      time varied from 64 min to 133 min (mean, 107.5 min), and the cardioplegia time
      varied from 40 min to 105 min. (mean, 76.7 min). All patients were in regular
      atrial rhythm at the end of surgery. The postoperative period was uneventful, and
      all patients were discharged from the hospital showing regular atrial rhythm,
      without definitive pacemaker implantation. In the postoperative period 6 months
      after surgery, 6 patients (75%) were in regular atrial rhythm with preserved
      atrial contractions, and 2 (25%) with atrial fibrillation, clinically controlled
      (New York Heart Association class II). There were no embolic complications or
      evidence of thrombosis in the echodopplercardiography control. CONCLUSION: It is
      concluded from this initial series of cases that the electrophysiolgical approach
      and the surgical technique employed improved the surgical treatment of atrial
      fibrillation, making possible the correction of mitral and tricuspid valve
      lesions without additional morbidity.

PMID- 16286279
TI  - Using the bilateral internal mammary artery in the left or right coronary artery
      system: 5-year comparison of operation techniques and angiographic results.
AB  - OBJECTIVE: Using the bilateral internal mammary artery (IMA) in coronary artery
      bypass grafting (CABG) surgery has prolonged survival, improved functional
      capacity, and reduced the rate of reintervention without increasing postoperative
      early morbidity and mortality. METHODS: Between January 1996 and December 1997,
      94 CABG operations were performed using the bilateral IMA. In Group A (n = 45),
      the right IMA was anastomosed to the left coronary artery system; in Group B (n =
      49), the right IMA was anastomosed to the right coronary artery system. The left
      IMA was always anastomosed to the left coronary artery system in both groups.
      RESULTS: There was 1 death (Group A) (1.06%), and 1 late death (Group B) (1.07%).
      One patient in Group A underwent balloon angioplasty, and 1 patient in Group B
      underwent reoperation after the follow-up. Pre- and postoperative data were
      similar between both groups, except for off-pump CABG, which was higher in Group
      B (2.2% versus 36.7%; P <.001). Twenty-three randomized patients in each group
      underwent control angiography until May 2002. Angiographic results showed that
      the patency of the right IMA to the right or left coronary artery system was
      similar (78.26% versus 82.6%; P = .7). But the left IMA had a better patency rate
      than the right IMA (95.65% versus 80.43%; P = .02). The patency rates of the left
      and right IMA anastomosis on the beating heart in Group B were not significantly
      different (92.3% versus 76.9%; P = .27). The patency of right IMA anastomosis
      with or without off-pump technique in Group B was similar (76.9% versus 80%; P =
      .84). CONCLUSIONS: Bilateral IMA can be used with low morbidity and mortality.
      The angiographic and clinical results of off-pump CABG show that bilateral IMA
      can also be used in off-pump surgery with similar results.

PMID- 16286281
TI  - Composite bilateral internal thoracic artery grafts via standard sternotomy for
      lateral wall revascularization in conscious patients.
AB  - BACKGROUND: A new technique has been developed that permits complete arterial
      revascularization of the lateral wall of the heart using in situ bilateral
      internal thoracic artery grafts in awake patients. This technique, performed
      without cardiopulmonary bypass or mechanical ventilation, creates the least
      invasive revascularization method for the lateral wall of the heart yet
      described. METHODS: In 4 patients, double or triple vessel coronary artery bypass
      grafting was performed without general anesthesia. A high thoracic epidural
      anesthesia was started 1 hour before surgery. Bilateral internal thoracic
      arteries were harvested and all anastomoses were performed with the off-pump
      technique via standard median sternotomy. Circumflex branches were anastomosed
      with the left internal thoracic artery via a heart positioner. RESULTS: All
      patients remained awake throughout the whole procedure. There was no
      perioperative myocardial infarction or mortality. Pneumothorax was observed in
      only 1 patient and did not hinder the procedure. There were no hemodynamic
      changes during lateral wall revascularization. Two patients required unexpected
      coronary endarterectomy during circumflex and right coronary artery anastomoses.
      CONCLUSIONS: Complete arterial revascularization via median sternotomy using in
      situ bilateral internal thoracic artery grafts without general anesthesia is a
      feasible and safe procedure for multivessel disease. This approach allows for
      complete coronary artery revascularization in patients with contraindications for
      general anesthesia with or without cardiopulmonary bypass.

PMID- 16286283
TI  - Future perspectives in astronomy and the earth sciences.
AB  - This article is an overview of the contributions to the Triennial Issue of Phil.
      Trans. R. Soc. A published in December, 2005, and also plays the role of a
      Preface. Devoted to the work of young scientists, the issue covers the fields of
      astronomy and earth science.

PMID- 16286285
TI  - The baryonic mass function of galaxies.
AB  - In the Big Bang about 5% of the mass that was created was in the form of normal
      baryonic matter (neutrons and protons). Of this about 10% ended up in galaxies in
      the form of stars or of gas (that can be in molecules, can be atomic, or can be
      ionized). In this work, we measure the baryonic mass function of galaxies, which
      describes how the baryonic mass is distributed within galaxies of different types
      (e.g. spiral or elliptical) and of different sizes. This can provide useful
      constraints on our current cosmology, convolved with our understanding of how
      galaxies form. This work relies on various large astronomical surveys, e.g. the
      optical Sloan Digital Sky Survey (to observe stars) and the HIPASS radio survey
      (to observe atomic gas). We then perform an integral over our mass function to
      determine the cosmological density of baryons in galaxies: Omega(b,gal)=0.0035.
      Most of these baryons are in stars: Omega(*)=0.0028. Only about 20% are in gas.
      The error on the quantities, as determined from the range obtained between
      different methods, is ca 10%; systematic errors may be much larger. Most (ca 90%)
      of the baryons in the Universe are not in galaxies. They probably exist in a
      warm/hot intergalactic medium. Searching for direct observational evidence and
      deeper theoretical understanding for this will form one of the major challenges
      for astronomy in the next decade.

PMID- 16286284
TI  - Cosmology with weak lensing surveys.
AB  - Weak gravitational lensing is responsible for the shearing and magnification of
      the images of high-redshift sources due to the presence of intervening mass.
      Since the lensing effects arise from deflections of the light rays due to
      fluctuations of the gravitational potential, they can be directly related to the
      underlying density field of the large-scale structures. Weak gravitational
      surveys are complementary to both galaxy surveys and cosmic microwave background
      observations as they probe unbiased nonlinear matter power spectra at medium
      redshift. Ongoing CMBR experiments such as WMAP and a future Planck satellite
      mission will measure the standard cosmological parameters with unprecedented
      accuracy. The focus of attention will then shift to understanding the nature of
      dark matter and vacuum energy: several recent studies suggest that lensing is the
      best method for constraining the dark energy equation of state. During the next 5
      year period, ongoing and future weak lensing surveys such as the Joint Dark
      Energy Mission (JDEM; e.g. SNAP) or the Large-aperture Synoptic Survey Telescope
      will play a major role in advancing our understanding of the universe in this
      direction. In this review article, we describe various aspects of probing the
      matter power spectrum and the bi-spectrum and other related statistics with weak
      lensing surveys. This can be used to probe the background dynamics of the
      universe as well as the nature of dark matter and dark energy.

PMID- 16286286
TI  - Jets, hotspots and lobes: what X-ray observations tell us about extra-galactic
      radio sources.
AB  - The brightest and most numerous discrete radio sources in the sky, radio galaxies
      and quasars, are powered by twin jets of plasma which emerge at relativistic
      speeds from very small regions at the centre of large elliptical galaxies,
      powered by mass infall on to supermassive black holes. The jets can carry
      material out to very large distances (millions of light years) where it forms
      balloon-like lobes. Until recently it has been impossible to make definite
      statements about the energy or the nature of the matter supplied by the jets, or
      the dynamics of the lobes as they expand into the external medium. This has meant
      that crucial questions about the generation of radio sources and their effect on
      their environment have gone unanswered. The situation has been revolutionized by
      the launch at the start of this decade of a new generation of X-ray
      observatories, Chandra and XMM-Newton. In this article, I explain why
      observations with these instruments have made such a difference, what we have
      learned as a result and why the community remains divided on some important
      features of the interpretation of the data.

PMID- 16286287
TI  - Organic matter in carbonaceous meteorites: past, present and future research.
AB  - Carbonaceous meteorites are fragments of ancient asteroids that have remained
      relatively unprocessed since the formation of the Solar System. These carbon-rich
      objects provide a record of prebiotic chemical evolution and a window on the
      early Solar System. Many compound classes are present reflecting a rich organic
      chemical environment during the formation of the planets. Recent theories suggest
      that similar extraterrestrial organic mixtures may have acted as the starting
      materials for life on Earth.

PMID- 16286288
TI  - An overview of coronal seismology.
AB  - The idea of exploiting observed oscillations as a diagnostic tool for determining
      the physical conditions of the coronal plasma was first suggested several decades
      ago (Roberts et al. 1984 Astrophys. J. 279, 857). Until recently, the application
      of this idea has been very limited by a lack of high-quality observations of
      coronal oscillations. However, during the last few years, this situation has
      changed dramatically, especially due to space-based observations by the Solar and
      Heliospheric Observatory and the Transition Region and Coronal Explorer and waves
      and oscillations have now been observed in a wide variety of solar structures,
      such as coronal loops, polar plumes and prominences. This paper will briefly
      summarize MHD wave theory, which forms the basis for coronal seismology, as well
      as present an overview of the variety of recently observed waves and oscillations
      in the solar corona. The present state of coronal seismology will also be
      discussed. Currently, the uncertainty associated with the obtained parameters is
      still considerable and, hence, the results require a cautious interpretation.
      However, these examples do show that coronal seismology is rapidly being
      transformed from a theoretical possibility to a viable technique.

PMID- 16286289
TI  - Imaging sunspots using helioseismic methods.
AB  - The origin of sunspots is one of the most fundamental and yet poorly understood
      areas in solar physics. Imaging local anomalous features in the solar interior
      offers a direct way to unravel the underlying physical processes of sunspots and
      the mechanisms behind their formation. The advent of local helioseismology in the
      last few years has, for the first time, made it possible to image local internal
      solar structures. High-resolution satellite and ground telescope data which
      reveal the details of the vibrations of the visible solar surface are essential
      in the development of local helioseismology. We are now in a position to transfer
      the seismic methods that have traditionally been used to study the Earth's
      interior to solar investigations. This interdisciplinary approach to developing
      seismic imaging techniques is opening up new ways of understanding the flow and
      other structural characteristics beneath sunspots. In this article, I review
      recent progress in the imaging of sunspots and the surrounding solar active
      regions. By highlighting the strengths of seismic methods and the challenges
      facing local helioseismology, I discuss some of the new research directions and
      possibilities that have arisen from this novel type of seismic imaging.

PMID- 16286291
TI  - The impact rate on Earth.
AB  - Recent data, and modelling of the interaction between asteroids and the
      atmosphere, has defined a complete size-frequency distribution for terrestrial
      impactors, from meteorite-sized objects up to kilometre-sized asteroids, for both
      the upper atmosphere and the Earth's surface. Although there remain significant
      uncertainties in the incidence of specific size-fractions of impactors, these
      estimates allow us to constrain the threat posed by impacts to human populations.
      It is clear that impacts remain a significant natural hazard, but uniquely, they
      are a threat that we can accurately predict, and take steps to avoid.

PMID- 16286290
TI  - Planetary heat flow measurements.
AB  - The year 2005 marks the 35th anniversary of the Apollo 13 mission, probably the
      most successful failure in the history of manned spaceflight. Naturally, Apollo
      13's scientific payload is far less known than the spectacular accident and
      subsequent rescue of its crew. Among other instruments, it carried the first
      instrument designed to measure the flux of heat on a planetary body other than
      Earth. The year 2005 also should have marked the launch of the Japanese LUNAR-A
      mission, and ESA's Rosetta mission is slowly approaching comet Churyumov
      Gerasimenko. Both missions carry penetrators to study the heat flow from their
      target bodies. What is so interesting about planetary heat flow? What can we
      learn from it and how do we measure it?Not only the Sun, but all planets in the
      Solar System are essentially heat engines. Various heat sources or heat
      reservoirs drive intrinsic and surface processes, causing 'dead balls of rock,
      ice or gas' to evolve dynamically over time, driving convection that powers
      tectonic processes and spawns magnetic fields. The heat flow constrains models of
      the thermal evolution of a planet and also its composition because it provides an
      upper limit for the bulk abundance of radioactive elements. On Earth, the global
      variation of heat flow also reflects the tectonic activity: heat flow increases
      towards the young ocean ridges, whereas it is rather low on the old continental
      shields. It is not surprising that surface heat flow measurements, or even
      estimates, where performed, contributed greatly to our understanding of what
      happens inside the planets. In this article, I will review the results and the
      methods used in past heat flow measurements and speculate on the targets and
      design of future experiments.

PMID- 16286292
TI  - The physical and chemical composition of the lower mantle.
AB  - This article reviews some of the recent advances made within the field of mineral
      physics. In order to link the observed seismic and density structures of the
      lower mantle with a particular mineral composition, knowledge of the
      thermodynamic properties of the candidate materials is required. Determining
      which compositional model best matches the observed data is difficult because of
      the wide variety of possible mineral structures and compositions. State-of-the
      art experimental and analytical techniques have pushed forward our knowledge of
      mineral physics, yet certain properties, such as the elastic properties of lower
      mantle minerals at high pressures and temperatures, are difficult to determine
      experimentally and remain elusive. Fortunately, computational techniques are now
      sufficiently advanced to enable the prediction of these properties in a self
      consistent manner, but more results are required.A fundamental question is
      whether or not the upper and lower mantles are mixing. Traditional models that
      involve chemically separate upper and lower mantles cannot yet be ruled out
      despite recent conflicting seismological evidence showing that subducting slabs
      penetrate deep into the lower mantle and that chemically distinct layers are,
      therefore, unlikely.Recent seismic tomography studies giving three-dimensional
      models of the seismic wave velocities in the Earth also base their
      interpretations on the thermodynamic properties of minerals. These studies reveal
      heterogeneous velocity and density anomalies in the lower mantle, which are
      difficult to reconcile with mineral physics data.

PMID- 16286294
TI  - Focused fluid flow in passive continental margins.
AB  - Passive continental margins such as the Atlantic seaboard of Europe are important
      for society as they contain large energy resources, and they sustain ecosystems
      that are the basis for the commercial fish stock. The margin sediments are very
      dynamic environments. Fluids are expelled from compacting sediments, bottom water
      temperature changes cause gas hydrate systems to change their locations and
      occasionally large magmatic intrusions boil the pore water within the sedimentary
      basins, which is then expelled to the surface. The fluids that seep through the
      seabed at the tops of focused fluid flow systems have a crucial role for seabed
      ecology, and study of such fluid flow systems can also help in predicting the
      distribution of hydrocarbons in the subsurface and deciphering the climate
      record. Therefore, the study of focused fluid flow will become one of the most
      important fields in marine geology in the future.

PMID- 16286295
TI  - The kaleidoscope ocean.
AB  - Oceanic plant life is dominated by the microscopic phytoplankton. Regardless of
      the scale at which they are observed, they display striking heterogeneity in
      their distribution. At their most dramatic they paint colorful swathes across
      whole seas. A short history of observations of phytoplankton 'patchiness' is
      presented, illustrated with some of the many ideas put forward to explain it.
      Focus is then turned to the mesoscale, covering scales of roughly 1-500 km. It is
      argued that the spatial variability seen in phytoplankton at these scales gives
      important information on the biogeochemistry of the ocean. In particular,
      interplay between the physical circulation and biological processes results in
      constantly shifting patterns that are strongly related to changes induced in
      phytoplankton production. It is thought that this physical influence may play a
      major role in controlling the rate at which new plant material (primary
      production) is generated in much of the world's oceans. Major questions yet to be
      addressed are also discussed including the difficulty of quantifying processes on
      the very limit of what we can model or observe and how these processes may change
      in response to and exert a feedback on future climate change.

PMID- 16286293
TI  - Mixing in seasonally stratified shelf seas: a shifting paradigm.
AB  - Although continental shelf seas make up a relatively small fraction (ca 7%) of
      the world ocean's surface, they are thought to contribute significantly (20-50%
      of the total) to the open-ocean carbon dioxide storage through processes
      collectively known as the shelf sea pump. The global significance of these
      processes is determined by the vertical mixing, which drives the net CO(2)
      drawdown (which can occur only in stratified water). In this paper, we focus on
      identifying the processes that are responsible for mixing across the thermocline
      in seasonally stratified shelf seas. We present evidence that shear instability
      and internal wave breaking are largely responsible for thermocline mixing, a
      clear development from the first-order paradigm for the water column structure in
      continental shelf seas. The levels of dissipation observed are quantitatively
      consistent with the observed dissipation rates of the internal tide and near
      inertial oscillations. It is perhaps because these processes make such a small
      contribution to the total energy dissipated in shelf seas that they are not well
      represented in current state-of-the-art numerical models of continental shelf
      seas. The results thus present a clear challenge to oceanographic models.

PMID- 16286296
TI  - Peatland hydrology and carbon release: why small-scale process matters.
AB  - Peatlands cover over 400 million hectares of the Earth's surface and store
      between one-third and one-half of the world's soil carbon pool. The long-term
      ability of peatlands to absorb carbon dioxide from the atmosphere means that they
      play a major role in moderating global climate. Peatlands can also either
      attenuate or accentuate flooding. Changing climate or management can alter
      peatland hydrological processes and pathways for water movement across and below
      the peat surface. It is the movement of water in peats that drives carbon storage
      and flux. These small-scale processes can have global impacts through exacerbated
      terrestrial carbon release. This paper will describe advances in understanding
      environmental processes operating in peatlands. Recent (and future) advances in
      high-resolution topographic data collection and hydrological modelling provide an
      insight into the spatial impacts of land management and climate change in
      peatlands. Nevertheless, there are still some major challenges for future
      research. These include the problem that impacts of disturbance in peat can be
      irreversible, at least on human time-scales. This has implications for the
      perceived success and understanding of peatland restoration strategies. In some
      circumstances, peatland restoration may lead to exacerbated carbon loss. This
      will also be important if we decide to start to create peatlands in order to
      counter the threat from enhanced atmospheric carbon.

PMID- 16286297
TI  - Volcano remote sensing with ground-based spectroscopy.
AB  - The chemical compositions and emission rates of volcanic gases carry important
      information about underground magmatic and hydrothermal conditions, with
      application in eruption forecasting. Volcanic plumes are also studied because of
      their impacts upon the atmosphere, climate and human health. Remote sensing
      techniques are being increasingly used in this field because they provide real
      time data and can be applied at safe distances from the target, even throughout
      violent eruptive episodes. However, notwithstanding the many scientific insights
      into volcanic behaviour already achieved with these approaches, technological
      limitations have placed firm restrictions upon the utility of the acquired data.
      For instance, volcanic SO(2) emission rate measurements are typically inaccurate
      (errors can be greater than 100%) and have poor time resolution (ca once per
      week). Volcanic gas geochemistry is currently being revolutionized by the recent
      implementation of a new generation of remote sensing tools, which are overcoming
      the above limitations and are providing degassing data of unprecedented quality.
      In this article, I review this field at this exciting point of transition,
      covering the techniques used and the insights thereby obtained, and I speculate
      upon the breakthroughs that are now tantalizingly close.

PMID- 16286298
TI  - Modelling climate change: the role of unresolved processes.
AB  - Our understanding of the climate system has been revolutionized recently, by the
      development of sophisticated computer models. The predictions of such models are
      used to formulate international protocols, intended to mitigate the severity of
      global warming and its impacts. Yet, these models are not perfect representations
      of reality, because they remove from explicit consideration many physical
      processes which are known to be key aspects of the climate system, but which are
      too small or fast to be modelled. The purpose of this paper is to give a personal
      perspective of the current state of knowledge regarding the problem of unresolved
      scales in climate models. A recent novel solution to the problem is discussed, in
      which it is proposed, somewhat counter-intuitively, that the performance of
      models may be improved by adding random noise to represent the unresolved
      processes.

PMID- 16286299
TI  - Mixing and transport in urban areas.
AB  - Concern over terrorist releases of harmful material has generated interest in
      short-range air-borne dispersion in urban areas. Here, we review the important
      fluid dynamical processes that control dispersion in the first kilometre, the
      neighbourhood scale, when much of the material remains within the urban canopy.
      Dispersion is then controlled by turbulent mixing and mean flow transport through
      the network of streets. We consider mixing and transport in a long straight
      street, street intersections and then a network of streets connected by
      intersections. The mixing and transport in these systems are illustrated with
      results from recent fine-resolution numerical simulations and laboratory models,
      which then inform simpler scaling estimates and modelling schemes. Finally, we
      make some tentative steps to pull the process studies together to begin to
      understand results from full-scale observations. In particular, it is shown that
      the positions of 'shear layers' and 'dividing streamlines' largely control the
      patterns of mixing and transport. It is also shown that neighbourhood-scale
      dispersion follows one scaling in the near field and another in the far field
      after passage through many intersections. The challenge for the future is to
      bring these threads together into a coherent mathematical model.

PMID- 16286300
TI  - Identification of fatty acid esters and hydrocarbon derivatives from Cyrtocarpa
      procera Kunth by GC-MS.
AB  - Extracts obtained from Cyrtocarpa procera Kunth were evaluated to determine their
      toxicity on Artemia salina Leach. All the extracts showed a significant activity.
      Bioguided fractionation of these extracts led to the isolation of beta-sitosterol
      and the identification of 1,3-propyl-dipentadecanoate, 3-hydroxypropyl-9
      octadecenoate, pentadecylbenzene, eicosylbenzene, docosane, heptacosane,
      dotriacontane and 2,6,10-trimethyltetradecane by GC-MS.

PMID- 16286301
TI  - Gamma-linolenic acid from Cape Verdian Boraginaceae.
AB  - The distribution of gamma-linolenic acid (GLA) was studied in the seed oil of six
      Cape Verdian Boraginaceae. The GLA ranges from trace levels in the three
      Heliotropum surveyed to 22.2% on saponifiable oil in Echium stenosiphon. All
      Echium species had GLA percentages in their seed oil around 20%. Echium seeds
      yield saponifiable oil from 15.8% (E. stenosiphon) to 17.3% (E. hypertropicum).

PMID- 16286302
TI  - Bioactive eremophilanolides from Senecio poepigii.
AB  - A new bioactive eremophilanolide, 1alpha-tigloyloxy-8betaH,10betaH-eremophil
      7(11)-en-8alpha,12-olide, was isolated from Senecio poepigii and its structure
      was elucidated by spectral analysis. 1alpha-Angeloyloxy-8beta-methoxy-10betaH
      eremophil-7(11)-en-8alpha,12-olide was also isolated. Antifungal and insect
      antifeedant properties were evaluated.

PMID- 16286303
TI  - Antibacterial activity of eight Brazilian annonaceae plants.
AB  - Sixteen extracts, obtained from eight Brazilian plants of Annonaceae family, were
      screened for their antibacterial activity: Xylopia frutescens, X. aromatica, X.
      amazonica, X. benthamii, Annona ambotay, A. crassiflora, A. muricata and A.
      cherimolia. Amongst the investigated extracts, six showed antibacterial activity
      against at least one of the tested organisms at the concentration of 100
      microg/mL. The most active extracts were those prepared from X. frutescens, X.
      amazonica, and A. ambotay. A phytochemical screening showed the presence of
      anonaceus acetogenins in some active extracts. Eleven diterpenoids were also
      tested for comparison purposes. Six were natural products, previously isolated
      from Xylopia sp. (kaurenoic, frutoic, xylopic, 15beta-hydroxy-kaurenoic and
      trachylobanic acids plus kaurenol) and five were derivatives of such compounds,
      obtained by esterification or reduction reactions. Trachylobanic acid showed
      antibacterial activity against B. subtilis and S. aureus.

PMID- 16286304
TI  - Two new isoflavonoids from Bowdichia virgilioides.
AB  - Two new isoflavonoids 7,8,4'-trimethoxyisoflavone and 7,8,4'
      trimethoxyisoflavanone and calycosin (7,3'-hydroxy-4'-methoxyisoflavone) were
      isolated from the wood of the leguminous tree Bowdichia virgilioides by usual
      chromatographic procedures. Besides these compounds the pterocarpane (-)
      maackianin, isoliquiritigenin (4,2',4'-trihydroxychalcone), and the
      hydrobenzylfurane derivative bowdenol were also obtained. The structures of these
      new compounds were determinated by MS and 1D and 2D NMR spectral analysis.

PMID- 16286305
TI  - Sesquiterpenoids from Vernonia cinerea.
AB  - A new sesquiterpenoid, namely vernocinolide A, as well as ten known ones, were
      isolated from the ethyl acetate soluble fraction of the Vernoniacinerea. The
      structure of vernocinolide A was elucidated by spectroscopic methods. Among the
      known sesquiterpenoids, nine of them were isolated from this plant for the first
      time.

PMID- 16286306
TI  - Cyclic diarylheptanoids inhibit cell mediated low-density lipoprotein oxidation.
AB  - Two cyclic diarylheptanoids, garugamblin-3 (1) and acerogenin L (2), isolated
      from the MeOH extract of the fruits of Alnus japonica Steud., inhibited human low
      density lipoprotein (LDL) oxidation in the thiobarbituric acid-reactive substance
      assay with IC(50) values of 2.9 and 1.7 microM, respectively, and they also
      inhibited cell-mediated LDL oxidation more than 5 times more strongly than that
      of a well-known antioxidant, probucol, at a concentration of 10 microM. Compound
      (1) had no effect on the anti-atherogenesis in low-density lipoprotein receptor
      deficient mice.

PMID- 16286307
TI  - 5-Methoxypropacin, a novel coumarinolignoid from Protium unifoliolatum.
AB  - The novel coumarinolignoid 5-methoxypropacin was isolated from the ethereal
      extract of the wood of the Amazonian species Protium unifoliolatum. Its structure
      was elucidated by spectroscopic methods as IR, 1D and 2D (1)H, (13)C-NMR and mass
      spectrometry. The regioisomer and the position of coumarin and arylpropanoid
      coupling were determined by long-distance C-H correlation (HMBC) and NOE
      experiments. Scopoletin and beta-sitosterol were also isolated and identified by
      the same physical methods.

PMID- 16286308
TI  - Isolation and structure revision of 10-deacetyltaxinine from the seeds of the
      Chinese yew, Taxus mairei.
AB  - A new taxoid was isolated from the methanol extract of the seeds of Taxus mairei.
      Its structures were established as 2alpha,9alpha-diacetoxy-10beta-hydroxy-5alpha
      cinnamoyloxytaxa-4(20), 11-dien-13-one (l0-deacetyltaxinine) on the basis of
      spectral analysis including (1)H-NMR, (13)C-NMR, HMQC, HMBC, NOESY, and HR-FABMS.
      The structure of previously reported 10-deacetyltaxinine is 9-deacetyltaxinine.

PMID- 16286309
TI  - Structural confirmation of decussatin, a Swertia decussata xanthone.
AB  - Reinvestigation of the plant, Swertia decussata resulted in the isolation of four
      antioxidant xanthones, which were characterized as 1-hydroxy-3,7,8-trimethoxy,
      1,8-dihydroxy-3,7-dimethoxy, 1,7-dihydroxy-3,8-dimethoxy and 1,7,8-trihydroxy-3
      methoxyxanthones. The structural ambiguity of the first compound was settled by
      ASIS-NMR and 2D NOESY spectroscopy.

PMID- 16286311
TI  - Glycosides from Bougainvillea glabra.
AB  - Three glycosides were isolated from Bougainvillea glabra and their structures
      were determined by extensive use of 1D and 2D NMR spectroscopy ((1)H and (13)C).
      First compound was identical to momordin IIc (quinoside D) [beta-D-glucopyranosyl
      3-O-[beta-D-xylopyranosyl-(1 --> 3)-O-(beta-D-glucopyranosyluronic acid)]
      oleanolate], second compound was quercetin 3-O-alpha-L-(rhamnopyranosyl)(1 --> 6)
      [alpha-L-rhamnopy-ranosyl(1 --> 2)]-beta-D-galactopyranoside and third compound
      was its derivative quercetin 3-O-alpha-L-(4-caffeoylrhamnopyranosyl)(1 --> 6)
      [alpha-L-rhamnopyranosyl (1 --> 2)]-beta-D-galactopyranoside, a new natural
      product.

PMID- 16286310
TI  - Antioxidant activity and two new flavonoids from Washingtonia filifera.
AB  - Two new flavonoids, 8-hydroxyisoscoparin (1) and luteolin 7-O-glucoside 4''
      sulfate (2), along with eight known flavonoids, including luteolin 7-O-glucoside
      2''-sulfate, were isolated and identified from Washingtonia filifera. All
      compounds were characterized by (1)H-NMR, (13)C-NMR, CI-MS, FABMS and UV. The
      antioxidant activities of various W. filifera extracts were determined.

PMID- 16286312
TI  - New ceramides from Platytaenia multicaule.
AB  - Phytochemical investigation of Platytaenia multicaule resulted in the isolation
      of two new ceramides, N-triacontylpentadecanamide and 1,3,4-trihydroxy
      2,dodecanoylamino-(24E)-unacotenene, along with two known compounds, beta
      sitosterol and beta-sitosterol glycoside. The structure elucidation of the
      isolated compounds was based primarily on 1D and 2D NMR analyses, including COSY,
      NOESY, HMQC, and HMBC correlations.

PMID- 16286313
TI  - A new alkylated benzoquinone from rhizomes of Iris kumaonensis.
AB  - A novel alkylated unsaturated p-benzoquinone designated as 3-[(z)-12'
      heptadecenyl]-2-hydroxy-5-methoxy-1,4-benzoquinone was isolated from hexane
      extract of the rhizomes of Iris kumaonensis and it's structure was confirmed by
      extensive spectroscopic analysis, IR, MS, HREIMS, 1D, 2D NMR and comparison with
      the literature data of known compounds.

PMID- 16286314
TI  - A new adenosyl-alkaloid from Ostrea rivularis.
AB  - A new adenosyl-alkaloid, ostrerine A, has been isolated along with an amino acid,
      tryptophan and a ribonucleoside, 2'-deoxythymidine from the Quanzhou marine
      mollusk, Ostrea rivularis, and the structures were elucidated by 1D and 2D NMR
      experiments, including (1)H-(1)H COSY, TOCSY, NOESY, HMQC, and HMBC methods.

PMID- 16286315
TI  - Comparative studies on the camptothecin content from Nothapodytes foetida and
      Ophiorrhiza species.
AB  - Camptothecin is an anticancer quinoline alkaloid effective against colon cancer.
      It acts by inhibition of the enzyme DNA topoisomerase I. A comparative study of
      camptothecin from the indigenous plants namely Nothapodytes foetida, Ophiorrhiza
      mungos and Ophiorrhiza rugosa indicated highest yields of camptothecin and 9
      methoxy camptothecin in N. foetida. The other two plants O. mungos and O. rugosa
      contained low levels of alkaloids.

PMID- 16286316
TI  - A new guaiane diterpenoid from Euphorbia wallichii.
AB  - A new guaiane-type diterpenoid, (1alpha,5beta,7alpha)-3,10(18),11-dictytriene-19
      acid, was obtained from the roots of Euphorbia wallichii. This is the first
      isolation of guaiane diterpene from this genus of Euphorbia. The structure was
      elucidated by spectral methods. And the compound was tested for the
      cytotoxicities on the cancer cell line P-388 and A-549 in vitro.

PMID- 16286318
TI  - Synthesis of beta-bisabolol by ring-closing olefin metathesis reaction.
AB  - A ring-closing olefin metathesis is the key step in the synthesis of the beta
      bisabolols.

PMID- 16286317
TI  - Total synthesis of anthocyanidins via Heck reaction.
AB  - Anthocyanidin moiety was obtained by cyclization of a 2-hydroxychalcone prepared
      by the Heck approach to the synthesis of flavonoids. 1-(3,4-dimethoxyphenyl)-prop
      2-en-1-one has been used as a coupling partner along with o-acetoxyiodobenzene in
      the Heck reaction.

PMID- 16286319
TI  - Surface flavonoid aglycones in newly studied plant species.
AB  - Several newly studied species of the Scrophulariaceae, Lamiaceae, and
      Ranunculaceae spread in Bulgaria have been analyzed for their surface flavonoid
      profiles. Except Pulsatilla montana (Hope) Rchb. (Ranunculaceae) all taxa now
      studied accumulated mainly apigenin, luteolin, and it's derivatives. This is the
      first report for the presence on external flavonoid aglycones in genus
      Pulsatilla. Quercetin-3'-methyl ether is a new citation for P. montana. The
      presence on surface flavonoid aglycones in species Veronica bellidioides L., V.
      persica Poir., Odontites verna (Bell.) Dum., Laminiastrum galeobdolon Heist ex
      Fabr., Glechoma herbaceae L., Ajuga genevensis L., and A. reptans L. are reported
      for the first time too.

PMID- 16286320
TI  - Social support and the physical activity behaviours of people with a brain
      injury.
AB  - PRIMARY OBJECTIVE: To examine the influence of social support on the physical
      activity behaviours of individual's with a traumatic brain injury. MAIN OUTCOMES
      AND RESULTS: The paper defines social support as a multi-dimensional construct
      and reviews relevant literature describing how the type and source of social
      support changes post-brain injury. These findings are then applied to a physical
      activity domain with the use of a conceptual framework. Discussion finally
      focuses on research applications and appropriate measures of social support
      within a physical activity environment. CONCLUSIONS: This paper will provide
      physical activity programmers with an understanding of how social support
      influences physical activity participation, a conceptual framework to guide
      programming and appropriate measures of social support for research purposes.

PMID- 16286321
TI  - A multi-perspective concept mapping study of problems associated with traumatic
      brain injury.
AB  - OBJECTIVE: To develop a model of the problems of persons with traumatic brain
      injury that includes multiple perspectives as well as the multi-dimensional
      nature of the phenomena. DESIGN: Concept mapping, a multi-variate modelling
      strategy, was employed to produce an exhaustive inventory and concept map of TBI
      related problems based on input from patients, family caregivers and professional
      providers. RESULTS: The eight-cluster concept map included the following
      dimensions: social competence, intimacy, behavioural, maturity/independence,
      neurophysiological, mood, executive functions and non-executive functions.
      CONCLUSIONS: An underlying two-dimensional conceptual model of TBI problems is
      proposed with relevance for theory, practice and further research.

PMID- 16286322
TI  - Prediction of the level of cognitive functional independence in acute care
      following traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To determine a predictive model for cognitive functional
      outcome of patients with traumatic brain injury (TBI) at discharge from acute
      care. METHODS AND PROCEDURE: Three hundred and thirty-five patients were included
      in this analysis. Variables considered were age, education, initial score on the
      Glasgow Coma Scale (GCS), duration of post-traumatic amnesia (PTA), cerebral
      imaging results and the need for neurosurgical intervention. EXPERIMENTAL
      INTERVENTIONS: Functional Independence Measure (FIM). MAIN OUTCOMES AND RESULTS:
      Results of this analysis indicated better cognitive FIM at discharge from acute
      care settings for patients with TBI when PTA was less than 24 hours, when level
      of education was higher, when no parietal lesion was identified, when no
      neurosurgical intervention was required, for patients with TBI who were younger
      and who presented with a higher GCS score upon admission. CONCLUSIONS: This model
      will help to plan resource allocation for treatment and discharge planning within
      the first weeks following TBI.

PMID- 16286323
TI  - Balance disorder and traumatic brain injury: preliminary findings of a multi
      factorial observational study.
AB  - The pathophysiology of TBI suggests that balance disorder in this population may
      be associated with multi-system dysfunction, but this has not been widely
      explored in the literature. This study was undertaken to begin to describe the
      nature of balance disorder across the TBI population. A clinically-based
      observational design was employed and data gathered by a standardized process of
      structured observation. Twenty-seven subjects were recruited across a range of
      injury severities. The sample was skewed towards mild/moderate injury with a mean
      summated GCS score of 9.6. Deficits were observed across a wide range of domains
      at both individual and group level and the overall level of balance dysfunction
      was high. Summary results are reported here and a more detailed analysis of
      individual cases is underway. Additional cross-disciplinary research is required
      to further develop understanding of the nature of balance disorder in this
      population and to develop appropriate methods of clinical assessment.

PMID- 16286324
TI  - Life satisfaction and distress in family caregivers as related to specific
      behavioural changes after traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To predict long-term outcome of those caring for family
      members who have sustained a traumatic brain injury (TBI). METHODS AND
      PROCEDURES: A multivariate approach was used to examine the effectiveness of
      caregiver coping strategies in the context of TBI-related behavioural change.
      Self-administered questionnaire packages were collected from 72 adult survivor
      and family-member pairs who provided information on survivors' altered executive
      function, behavioural control and emotional sensitivity as well as caregivers'
      methods of coping, attitudes toward caregiving, indices of distress, mood ratings
      and quality of life. MAIN OUTCOMES AND RESULTS: Family members generally reported
      higher levels of satisfaction than dissatisfaction with their caregiving role.
      The type of neurobehavioural deficit and the approaches taken to cope with stress
      had specific effects on each dimension of caregiver outcome. CONCLUSIONS:
      Adequate family support requires finely tuned assessment of factors relevant to
      successful coping.

PMID- 16286325
TI  - How severe should symptoms be before someone is said to be suffering from post
      concussion syndrome? An exploratory study with self-reported checklist using
      Rasch analysis.
AB  - PRIMARY OBJECTIVE: This study aimed to examine the diagnosis of post-concussive
      symptoms among a group of people with subjective post-concussive symptoms (PCS)
      complaints using a self-reported checklist. RESEARCH DESIGN: A cross-sectional
      design was adopted with a total of 92 patients with PCS and 123 normal controls.
      METHODS AND PROCEDURES: The Rivermead Post-concussion Symptoms Questionnaire was
      administered to all participants. Analysis using the Rasch Model was undertaken.
      MAIN OUTCOMES AND RESULTS: The common matrix of symptom profiles indicated
      significant effects of gender (p < 0.005) and litigation (p < 0.0004). The
      patient group reported significantly higher symptoms than the healthy group (p <
      0.0001) with differential symptom endorsement along the logits unit continuum.
      CONCLUSIONS: The application of Rasch model analysis successfully set up a common
      matrix to discriminate patients with post-concussive symptoms from healthy people
      along the logits unit continuum.

PMID- 16286326
TI  - Elevated dark adaptation thresholds in traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To expand upon earlier findings of elevated dark adaptation
      (scotopic) thresholds in photosensitive individuals with traumatic brain injury
      (TBI). METHODS AND PROCEDURES: To assess scotopic thresholds in individuals with
      TBI (n = 17) manifesting varying degrees of photosensitivity (mild, moderate or
      marked), but without retinal dysfunction, to those of non-photosensitive,
      visually-normal individuals (n = 21) using a hand-held dark adaptometer. MAIN
      OUTCOMES AND RESULTS: The group mean scotopic threshold for the TBI group was
      significantly higher than that of the visually-normal group. Over 50% (nine out
      of 17) of the TBI group exhibited elevated thresholds. There was no correlation
      between the threshold value and degree of photosensitivity. CONCLUSION: The
      elevated scotopic thresholds suggest an abnormality in cortical gain control. An
      anomalous adaptive response may develop due to cortical damage, thereby
      attenuating subjective light sensation.

PMID- 16286327
TI  - Microlinguistic deficits in the narrative discourse of adults with traumatic
      brain injury.
AB  - BACKGROUND: Recent studies of microlinguistic impairments in the narrative
      discourse of adults with traumatic brain injury (TBI) have applied syntactic
      analyses, with some noting no deficits and others specific problems with sentence
      formulation. An alternative approach to examining the microlinguistic dysfunction
      in the discourse of individuals with TBI is through the use of propositional
      analysis. The advantage of propositional analysis is that it enables one to
      assess semantic complexity of utterances apart from sentence structure and
      grammaticality. AIMS: The present study applied propositional analysis to the
      story narratives of participants with TBI and participants with no brain injury
      (NBI). Specifically, the mean number of propositions within a sentence was
      tallied, in other words the participants' ability to insert multiple ideas into
      single surface sentences. It was hypothesized that the participants with TBI
      would produce fewer propositions per sentence because of organizational problems
      than the participants with NBI, regardless of level of education. METHODS AND
      PROCEDURES: Two story narratives (retelling and generation) previously elicited
      from the two participant groups (TBI (n = 53) and NBI (n = 42)) were analysed.
      For each language sample, the number of propositions was tallied and divided by
      the number of T-units. The resulting number, the propositional complexity index
      (PCI), was the average number of predicates per sentence. OUTCOMES AND RESULTS:
      Results indicated that the group with TBI produced significantly fewer
      propositions per T-unit. CONCLUSIONS: The present findings are in harmony with
      the notion that the participants with TBI studied presented with impairments of
      both micro- and macrolinguistic processes involved with the organization of
      semantic information in discourse. Clinical implications are discussed.

PMID- 16286328
TI  - Anoxic brain injury following near-drowning in children. Rehabilitation outcome:
      three case reports.
AB  - PRIMARY OBJECTIVE: To describe the outcome of near-drowning and rehabilitation
      contexts for recovery. METHODS AND PROCEDURES: Standardized measures were used to
      emphasize the functional impact of deficits over the first year post-injury in
      three children <2 years. Multimodal contexts for meaningful interplay were early
      adapted to the three cases. MAIN OUTCOMES AND RESULTS: The clinical pathways of
      recovery are identified. Initially all three cases manifested a generalized
      dystonia. Case 1 exhibited a good outcome with transient dyskinetic-dystonic
      syndrome; subsequently Balint's syndrome emerged. In this case, the
      rehabilitation approach was organized on the pickup of direct perception of task
      specific affordances. Cases 2 and 3 had poor outcomes presenting the worsening of
      torsion dystonia (status dystonicus) that hindered rehabilitation intervention.
      CONCLUSIONS: The dynamic reaggregation of spatial organization through meaningful
      interaction in specific ecological contexts is the principal goal of
      rehabilitation intervention. Status dystonicus represents the worst feature for
      recovery.

PMID- 16286329
TI  - Rehabilitation of verbal working memory after left hemisphere stroke.
AB  - PRIMARY OBJECTIVE: To assess a rehabilitation programme of working memory.
      RESEARCH DESIGN: Single case multiple-baseline-across-behaviour design in a
      patient with chronic stroke suffering from a specific impairment of working
      memory. METHODS: Rehabilitation included training of storage and processing
      components of verbal working memory. Outcome was assessed with specific working
      memory tests, non-specific tasks requiring working memory, non-target tasks not
      requiring working memory and questionnaires addressing daily-life functioning.
      This assessment was performed twice before the experimental therapy and once
      after. RESULTS: Cognitive measures were stable before therapy. A statistically
      significant improvement was found for target measures and for daily-life skills.
      In contrast, no change was found on non-target tasks. CONCLUSION: Improvement was
      not apparently related to spontaneous recovery, since performance was stable
      before therapy. This study suggests that specific cognitive training may improve
      working memory in patients with brain injury.

PMID- 16286330
TI  - Assessing recovery in middle cerebral artery stroke using functional MRI.
AB  - PRIMARY OBJECTIVE: To understand the temporal evolution of brain reorganization
      during recovery from stroke. RESEARCH DESIGN: A patient who suffered left middle
      cerebral artery stroke 9 months earlier was studied on three occasions,
      approximately 1 month apart. METHODS AND PROCEDURES: Brain activation was studied
      using functional Magnetic Resonance Imaging (fMRI). During each session, the
      patient performed a finger-to-thumb opposition task, which involved one bimanual
      and two unimanual conditions. Each condition consisted of overt movement of
      fingers and imagery of the same task. RESULTS: With recovery, greater recruitment
      was observed of the affected primary motor cortex (M1) and a decrease in
      activation of the unaffected M1 and supplementary motor area. In addition, the
      widespread activation of brain areas seen during the initial session changed to a
      more focused pattern of activation as the patient recovered. Imagery tasks
      resulted in similar brain activity as overt execution pointing to imagery as a
      potential tool for rehabilitation.

PMID- 16286333
TI  - Coping strategies, social support, life orientation and health-related quality of
      life following traumatic brain injury.
AB  - OBJECTIVE: To study coping strategies, social support and life orientation in
      patients following moderate and severe traumatic brain injury (TBI) in relation
      to health-related quality of life. SUBJECTS: Eighty-five patients with moderate
      or severe TBI and 68 control persons. METHODS: Estonian versions of the COPE-D
      test, the Brief Social Support Questionnaire, the Life Orientation Test and the
      RAND-36 questionnaire. RESULTS: Persons with TBI reported using task-oriented and
      social/emotional support strategies less often and avoidance-oriented strategies
      more often than control persons (p < 0.05). The social support network,
      satisfaction with it and optimism as life orientation were lower in the patient
      group (p < 0.05). Task-oriented coping styles, satisfaction with social support
      and optimistic life orientation were associated with the majority of the domains
      of health-related quality of life and resuming work after TBI. CONCLUSIONS: To
      achieve effective rehabilitation and to enhance patients' well-being, it is
      important to improve the quality and amount of social support network, as well as
      to support patients' adequate coping efforts for promoting an active lifestyle.

PMID- 16286334
TI  - Test-re-test reliability of the virtual planning test.
AB  - PRIMARY OBJECTIVE: To determine test-re-test reliability of the virtual planning
      test (VIP), an executive functioning test of planning and organization, in a
      group of healthy young adults as a pre-cursor to determining the appropriateness
      of using the VIP with individuals with traumatic brain injury (TBI). RESEARCH
      DESIGN: Single-group repeated measures design. METHODS AND PROCEDURES: Seventy
      five healthy university students were administered the VIP and the Hopkins Verbal
      Learning Test-Revised (HVLT-R) twice, with 6-8 weeks between each subject's two
      test sessions. MAIN OUTCOMES AND RESULTS: VIP test-re-test reliability ranged
      from 0.194-0.489. CONCLUSIONS: Knowing how well a healthy young adult performs
      the first time taking the VIP predicts little about how well that adult will
      perform the second time. However, given limitations of other tests of planning
      and organization and potential clinical benefits of the VIP, research of the test
      with individuals with TBI is warranted.

PMID- 16286335
TI  - Amantadine to enhance readiness for rehabilitation following severe traumatic
      brain injury.
AB  - PRIMARY OBJECTIVE: To evaluate the association between amantadine and recovery of
      consciousness from prolonged traumatic coma. RESEARCH DESIGN: A retrospective
      cohort study. METHODS: Subjects included 123 adults with severe traumatic brain
      injury (TBI) admitted over a 10-year period who remained in coma despite becoming
      medically stable. EXPERIMENTAL INTERVENTIONS: Cases received 100-200 mg of
      amantadine twice daily. MAIN OUTCOMES AND RESULTS: 46.4% (13/28) of cases emerged
      from coma compared to 37.9% (36/95) of controls (p = 0.42). Somatosensory evoked
      potential (SSEP) was the only significant predictor of emergence from coma (p =
      0.02), while SSEP, age and Glasgow Coma Score (GCS) significantly predicted time
      to emerge from coma (p < 0.05). CONCLUSIONS: Although the study and its design do
      not support the view that amantadine has an effect on recovery of consciousness;
      it remains safe, inexpensive and has few side effects. The lack of treatment
      alternatives and anecdotal support for its use may warrant further study.
      Prospective controlled trials would yield more definitive results.

PMID- 16286337
TI  - A 5-year follow-up study of an atypical case of myotonic dystrophy.
AB  - This study presents 5-year follow-up data on NG, a woman with adult onset
      myotonic dystrophy and progressive cognitive decline who was first described by
      Wilson et al. The extent of the cognitive impairment is atypical of symptom-onset
      in adulthood and of paternal inheritance, both of which apply to this case.
      Together, the present and earlier studies report the results of regular
      neuropsychological assessments over a 16-year period. Severe impairment in
      executive functioning, episodic and semantic memory were apparent early in the
      history, while visuospatial skills and working memory were only mildly impaired
      after 16 years of follow-up. There was also a progressive dyslexia, initially
      characterized by the regularization errors typical of surface dyslexia, but
      subsequently dominated by visual/phonological reading errors. This pattern of
      impairment is not typical of myotonic dystrophy but resembles semantic dementia.
      Whilst the deficits may be attributable wholly to myotonic dystrophy pathology,
      the co-existence of a form of semantic dementia is also possible. It is noted
      that the aggregation of tau protein is a neuropathological feature common to both
      diseases.

PMID- 16286336
TI  - Changes in bone metabolism in a rat model of traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To evaluate the process of bone metabolism after traumatic
      brain injury. RESEARCH DESIGN: Randomized controlled trial. METHODS AND
      PROCEDURES: Rats were randomly assigned to either the brain injury group or to
      the sham-operation group using a fluid percussion device. The BMDs of lumbar
      vertebrae and proximal femur and bone turnover markers, osteocalcin and carboxy
      terminal telopeptide, were measured at three points: the day before surgery and 1
      and 3 weeks post-operatively. The biomechanics (maximum load of tibia and femoral
      neck) were measured 3 weeks post-operatively. MAIN OUTCOMES AND RESULTS: There
      was significant change in the BMDs of lumbar vertebrae 1 week post-operatively
      and of both distal femurs 3 weeks post-operatively (p < 0.05). A significant
      change in the maximum load of femoral neck was also observed 3 weeks post
      operatively between the brain injury and the sham-operation groups (p = 0.044).
      CONCLUSIONS: This finding suggests that brain injury could induce osteoporosis by
      immobilization.

PMID- 16286338
TI  - Psychological and marital adjustment in couples following a traumatic brain
      injury (TBI): a critical review.
AB  - The first part of this paper examines current data describing the psychological
      and marital adjustment of couples following a traumatic brain injury (TBI).
      Although these findings reveal some discrepancies, they highlight that adjustment
      following a TBI represents a genuine challenge for those involved in the process.
      The second part moves toward the examination of factors associated with
      psychological and marital adjustment in both couple partners. Here again, there
      exists a large diversity in empirical data and theoretical models informing this
      emerging area of interest. Nevertheless, cognitive variables such as coping
      skills are commonly seen as critical variables to explain the adjustment level in
      people with TBI and their spouse/caregivers. Concurrently with the discussion of
      the methodological issues and pitfalls encountered in this area of research, the
      conclusion provides suggestions of further steps to undertake in this endeavour
      toward a better understanding of the adjustment process following TBI.

PMID- 16286339
TI  - Cognitive rehabilitation after severe traumatic brain injury: a pilot programme
      of goal planning and outdoor adventure course participation.
AB  - PRIMARY OBJECTIVE: To describe and evaluate a pilot community based
      rehabilitation programme for severe brain injury. RESEARCH DESIGN: A prospective
      repeated-measures design with a single convenience sample was conducted. METHODS
      AND PROCEDURES: Eleven participants with a history of severe brain injury
      completed the programme, which featured an outdoor adventure course, skill
      development and goal-based learning. In the first stage, practical activities
      facilitated the development of social skills, group cohesiveness and community
      integration. The second stage was a 9-day outdoor adventure course, which
      included physically challenging activities such as camping, bushwalking,
      abseiling, caving and high rope work. The third stage encouraged individuals to
      work on the personal goals they had developed. MAIN OUTCOMES AND RESULTS: Over
      80% of stated goals were achieved; suggesting that such a programme may be
      effective in enabling clients to attain specified goals. CONCLUSIONS: The
      programme shows promise as a form of community rehabilitation.

PMID- 16286340
TI  - Characteristics of home-based community integration programmes for adults with
      brain injury.
AB  - OBJECTIVES: To conduct a nationwide telephone survey in order to gather data on
      some of the quantifiable characteristics of home-based community integration
      programmes available in the US to adults with brain injury. DESIGN: Survey.
      METHODS: The Community Integration Programme Questionnaire (CIPQ) was used to
      interview 13 home-based community integration programmes. This study then used
      descriptive statistics to analyse the characteristics of the programmes. OUTCOME:
      There was a good deal of variability in client and programmatic characteristics.
      CONCLUSIONS: There is considerable variability in characteristics among home
      based community integration programmes.

PMID- 16286341
TI  - A profile of community navigation in adults with chronic cognitive impairments.
AB  - PRIMARY OBJECTIVE: This study sought to identify navigation patterns and
      illuminate the barriers to and possible solutions for independent community
      travel in people with chronic cognitive impairments as a result of acquired brain
      injury. RESEARCH DESIGN: Two investigative methods were used to explore
      navigation in the population of interest: Study 1 was a field study and study 2
      convened a series of focus groups with relevant stakeholders. METHODS AND
      PROCEDURES: For study 1, each week during a 4 month period, researchers
      administered a navigational survey and structured interview to a typical case
      sample of six participants in order to catalogue all trips taken outside the
      assistive living facility. Study 2 convened six focus groups to access
      perspectives on navigational issues for individuals with cognitive impairments
      (CI) from a number of stakeholder groups including individuals with CI, care
      providers for this population and public transportation workers. CONCLUSIONS: The
      results of both studies were consistent and indicated that community access is
      severely restricted for individuals with CI. The majority of trips that were
      taken tended to be routine and assisted. The variety of travel was limited;
      participants ventured to the same set places with the same people. Participants
      described barriers accounting for these problems and suggested a number of
      strategies to minimize problems.

PMID- 16286342
TI  - The symptom checklist-90-revised and mild traumatic brain injury.
AB  - OBJECTIVE: Assessment of emotional functioning is a critical aspect of the
      clinical neuropsychological evaluation of individuals following mild traumatic
      brain injury (MTBI). The objective of this study was to examine the utility of
      the Symptom Checklist-90-Revised as a brief tool for assessing psychological and
      symptomatic distress following MTBI. METHOD: A contrasted groups approach,
      involving three clinical groups (MTBI, Whiplash Associated Disorder, Type I
      Diabetes) and a non-clinical control group, was used in this study. RESULTS: The
      group with MTBI scored significantly higher on the majority of primary symptom
      dimensions and global distress indices of the SCL-90-R compared to both the
      diabetes and non-clinical control groups. Analysis of individual cases further
      revealed that 68.2% of the participants in the group with MTBI were classified as
      positive cases, a rate significantly higher than that of the diabetes and non
      clinical control groups. The group with MTBI did not differ significantly from
      the group of individuals with whiplash associated disorder with respect to
      elevation of primary symptom dimensions or global distress indices, or the number
      of cases classified as positive. CONCLUSION: The results of this study suggest
      that the SCL-90-R has considerable utility as a general measure of psychological
      and symptomatic distress following MTBI.

PMID- 16286343
TI  - Unusually rapid and severe cognitive deterioration after mild traumatic brain
      injury.
AB  - A 56-year-old man (AB) presented with dramatic cognitive deterioration following
      a mild traumatic brain injury. There was no indication of severe brain injury or
      significant anoxic encephalopathy. Detailed history indicated no significant pre
      morbid cognitive deficits. His pre-injury psychosocial and occupational
      functioning was intact. Cognition functioning was impaired immediately post
      injury and remained impaired. Neuropsychological examination at 8 months post
      injury showed severe cognitive deficits. The cognitive profile was consistent
      with Alzheimer's disease. MRI at 1-year post-injury showed minor ischaemic
      changes not consistent with hypoxic injury and insufficient to explain his
      cognitive problems. Early SPECT was consistent with a diagnosis of Alzheimer's
      disease and a repeat SPECT showed a significant deterioration in an Alzheimer
      pattern. AB was seen for detailed serial neuropsychological examination over a 3
      year period, which revealed clear evidence of cognitive deterioration consistent
      with Alzheimer's disease. AB is presented as an unusual case of rapid progressive
      AD following a mild head injury.

PMID- 16286344
TI  - Paroxysmal episodic hypothalamic instability with hypothermia after traumatic
      brain injury.
AB  - This case report describes a patient in vegetative state after severe traumatic
      brain injury (TBI) with hypothalamic damage and clinical manifestations of
      autonomic dysfunction. He also presented late onset paroxysmal hypothermia
      associated with mild bradycardia and hypotension. Hypothermia due to traumatic
      lesions of the hypothalamus is an uncommon clinical problem and few cases have
      been reported; no cases could be found in the literature which evidenced periodic
      hypothermia associated with clinical features of autonomic dysfunction after TBI.
      In the article, the main causes and the primary pathophysiology of hypothermia
      after TBI are discussed. The manifestations in this patient have been interpreted
      as possible consequences of autonomic dysfunction and considered atypical and
      rare clinical expression of acute post-traumatic hypothalamic instability.

PMID- 16286345
TI  - Cognitive recovery from Encephalitis Lethargica.
AB  - The cognitive profile and outcome of Encephalitis Lethargica has not been
      systematically described in the literature. Treatment has typically focused upon
      medical management. The first case report of a patient with Encephalitis
      Lethargica who underwent a systematic programme of cognitive rehabilitation is
      presented. Initial neuropsychological assessment conducted during her acute
      presentation indicated generalized cognitive dysfunction, including memory and
      executive function impairments. An outpatient cognitive rehabilitation programme
      addressed the development of awareness and the remediation of memory and
      executive function impairments. Repeat assessment indicated significant
      improvement in cognitive function. The components of her rehabilitation programme
      are discussed. She has been able to successfully return to her pre-morbid level
      of work responsibility within 8 months of her admission.

PMID- 16286347
TI  - Pre-emptive analgesia with thoracic paravertebral blockade?

PMID- 16286348
TI  - The laryngeal tube.
AB  - The laryngeal tube (VBM Medizintechnik, Sulz, Germany) is a relatively new
      extraglottic airway, designed to secure a patent airway during either spontaneous
      breathing or controlled ventilation. In this review article, we have assessed the
      potential role of the laryngeal tube during anaesthesia and during
      cardiopulmonary resuscitation. There are four variations of the laryngeal tube:
      standard laryngeal tube, disposable laryngeal tube, laryngeal tube-Suction II and
      disposable laryngeal tube-Suction II. The design of the device has been revised
      several times. Insertion of the standard laryngeal tube is as easy as with the
      laryngeal mask airway classic. The laryngeal tube may provide a better sealing
      effect than the laryngeal mask. The incidence of complications with the two
      devices is similar, although the laryngeal tube may require more re-adjustments
      of its position to obtain a clear airway. Compared with the ProSeal laryngeal
      mask, the laryngeal tube may be less effective. The efficacy of the standard
      laryngeal tube is unclear, particularly in patients breathing spontaneously or in
      children. The efficacy of the laryngeal tube Suction-II and disposable devices is
      also not clear. From the limited number of studies and reports available, it can
      be concluded that the laryngeal tube is potentially useful in maintaining a clear
      airway during anaesthesia and cardiopulmonary resuscitation. In addition, the
      device may be useful as an aid to tracheal intubation.

PMID- 16286349
TI  - Predicting fluid responsiveness in patients undergoing cardiac surgery:
      functional haemodynamic parameters including the Respiratory Systolic Variation
      Test and static preload indicators.
AB  - BACKGROUND: Prediction of the response of the left ventricular stroke volume to
      fluid administration remains an unsolved clinical problem. We compared the
      predictive performance of various haemodynamic parameters in the perioperative
      period in patients undergoing coronary artery bypass surgery. These parameters
      included static indicators of cardiac preload and functional parameters, derived
      from the arterial pressure waveform analysis. These included the systolic
      pressure variation (SPV) and its delta down component (dDown), pulse pressure
      variation (PPV), stroke volume variation (SVV), and a new parameter, termed the
      respiratory systolic variation test (RSVT), which is a measure of the slope of
      the lowest systolic pressure values during a standardized manoeuvre consisting of
      three successive incremental pressure-controlled breaths. METHODS: Eighteen
      patients were included into this prospective observational study. Seventy volume
      loading steps (VLS), each consisting of 250 ml of colloid administration were
      performed before surgery and after the closure of the chest. The response to each
      VLS was considered as a positive (increase in stroke volume more than 15%) or non
      response. Receiver operating characteristic curves were plotted for each
      parameter to evaluate its predictive value. RESULTS: All functional parameters
      predicted fluid responsiveness better than the intrathoracic blood volume and the
      left ventricular end-diastolic area. Parameters with the best predictive ability
      were the RSVT and PPV. CONCLUSIONS: Functional haemodynamic parameters are
      superior to static indicators of cardiac preload in predicting the response to
      fluid administration. The RSVT and PPV were the most accurate predictors of fluid
      responsiveness, although only the RSVT is independent of the settings of
      mechanical ventilation.

PMID- 16286350
TI  - Isoflurane-induced myocardial preconditioning is dependent on
      phosphatidylinositol-3-kinase/Akt signalling.
AB  - BACKGROUND: Isoflurane and other volatile anaesthetics have a cardioprotective
      effect and limit myocardial infarct size to the same extent as ischaemic
      preconditioning. Phosphatidylinositol-3-kinase (PI3K) was found to play a key
      role in myocardial protection by ischaemic preconditioning. The aim of the
      present investigation was to evaluate whether isoflurane-induced myocardial
      preconditioning is dependent on PI3K signalling. METHODS: Using a model of
      regional myocardial ischaemia and reperfusion, New Zealand White rabbits were
      subjected to 40 min of regional myocardial ischaemia followed by 120 min of
      reperfusion. The rabbits were randomly assigned to one of the following six
      experimental groups: sham-operated controls (n=5); ischaemia and reperfusion
      controls (n=8); isoflurane preconditioning (n=8); a PI3K inhibitor, wortmannin
      (0.6 mg kg(-1) i.v.) + isoflurane (n=8); and wortmannin+ischaemia and reperfusion
      (n=8). An additional control group of sham operation+ wortmannin (n=5) was also
      included. Myocardial injury was assessed by measuring the serum concentration of
      the MB fraction of creatine kinase (CK-MB) and infarct size was assessed by 2,3,5
      triphenyl tetrazolium chloride staining. Phosphorylation of Akt, a downstream
      target of PI3K, was assessed by western blotting. RESULTS: Isoflurane
      preconditioning was seen as reduced infarct size compared with control animals:
      24 (4) and 41 (5)% respectively (P<0.05). Wortmannin inhibited this
      cardioprotective effect with myocardial infarct size at 44 (3)% (not
      significant). Akt phosphorylation was increased after isoflurane preconditioning,
      but administration of wortmannin blocked this effect. CONCLUSIONS: Our data
      demonstrate that isoflurane protects the heart against ischaemia and decreases
      myocardial infarction by activation of PI3K.

PMID- 16286351
TI  - Chronic beta-adrenoreceptor blockade in surgical patients.

PMID- 16286352
TI  - Additional use for adenosine in anaesthesia and surgery.

PMID- 16286353
TI  - Follow-up ward rounds after intensive care--what do the patients and their
      visitors think?

PMID- 16286354
TI  - Epidural stimulation test vs epidural ECG test for checking epidural catheter
      placement.

PMID- 16286355
TI  - Permanent anosmia after topical nasal anaesthesia with lidocaine 4%.

PMID- 16286356
TI  - "Gas off" or "vaporizer off".

PMID- 16286357
TI  - Thrombotic-thrombocytopenic purpura following malaria prophylaxis with
      mefloquine.

PMID- 16286358
TI  - Effects of clofazimine on potassium uptake by a Trk-deletion mutant of
      Mycobacterium tuberculosis.
AB  - OBJECTIVES: This study was designed to investigate the effects of the membrane
      active, anti-mycobacterial agent, clofazimine, on potassium (K+)-uptake by a
      mutant of Mycobacterium tuberculosis (MTB), in which the Trk system, the major K+
      transporter of this microbial pathogen, had been selectively inactivated.
      METHODS: The ceoB and ceoC genes of MTB, which encode the TrkA proteins, CeoB and
      CeoC, were deleted by homologous recombination, and the double-knockout mutant
      and wild-type strains compared with respect to K+ uptake and growth in the
      presence and absence of clofazimine (0.015-2.5 mg/L) using radioassay procedures.
      RESULTS: Surprisingly, the magnitudes of K+ uptake and rate of growth of the
      ceoBC-knockout mutant were significantly (P < 0.05) greater than those of the
      wild-type strain, due, presumably, to induction of a back-up transporter.
      Exposure of both the wild-type strain and ceoBC-knockout mutant of MTB to
      clofazimine was accompanied by dose-related decreases in K+ uptake, as well as
      growth, which were of comparable magnitude for both strains. CONCLUSIONS: These
      observations demonstrate that the major K+ transporter of MTB, Trk, as well as an
      uncharacterized inducible back-up system, is equally sensitive to the inhibitory
      actions of clofazimine.

PMID- 16286359
TI  - Deletion of pT181-like sequence in an smr-encoding mosaic plasmid harboured by a
      persistent bovine Staphylococcus warneri strain.
AB  - OBJECTIVES: The aim was to study the persistence and characteristics of
      Staphylococcus warneri strains resistant to quaternary ammonium compounds (QACs),
      including sequencing and analysis of two plasmids proved to carry the smr gene.
      METHODS: During a 3.5 year period quarter milk samples were collected on three
      occasions from all lactating cows in a dairy herd. The samples were screened with
      regard to QAC-resistant bacteria using a selective medium. Thirty randomly
      selected QAC-resistant S. warneri were typed by PFGE and subjected to plasmid
      isolation and analysis followed by gene detection using PCR. Two smr-containing
      plasmids in S. warneri isolates were sequenced. RESULTS: All isolates from the
      initial collection of quarter milk contained smr residing on a 5.8 kb plasmid
      (pSW174), which contained regions with high similarities to various plasmids,
      including pT181, pSK108 and pPI-2. The pT181-like sequence was flanked by 148 bp
      direct repeats, denoted ISLE49, with high similarity to previously reported
      sequences of approximately 148 bp, including ISLE39 flanking the insertion
      sequence IS257 in methicillin-resistant Staphylococcus aureus. All isolates from
      subsequent collections of quarter milk harboured a smaller smr-containing plasmid
      (pSW49). Sequence analyses revealed pSW49 (3552 bp) to be an in-part deleted
      version of pSW174 (5767 bp). CONCLUSIONS: The IS-associated elements found in
      this study may have a wider role in the integration and excision of DNA sequences
      in staphylococci than previously reported. The mosaic plasmid structure based on
      genetic elements of various origins contributes to further knowledge on the
      flexibility of smr-encoding plasmids.

PMID- 16286360
TI  - Molecular epidemiology of emergent multidrug-resistant Salmonella enterica
      serotype Typhimurium strains carrying the virulence resistance plasmid pUO-StVR2.
AB  - OBJECTIVES: To evaluate the incidence of a distinct multidrug-resistant (MDR)
      grouping of Salmonella serotype Typhimurium strains carrying the hybrid virulence
      resistance plasmid pUO-StVR2, and its possible evolution in the region where it
      was first detected [Principality of Asturias (PA), Spain]. METHODS: pUO-StVR2
      containing isolates were tentatively identified by two genetic markers: the
      bla(OXA-30) gene and the class 1 integron InH:2000 bp/bla(OXA-30)-aadA1a.
      Positive isolates were examined for resistance profile (RP), plasmid content,
      virulence profile (VP) and genomic polymorphisms using macrorestriction-PFGE.
      RESULTS: A total of 182 out of 248 Typhimurium clinical isolates recorded in the
      PA over 2001-02 were ampicillin-resistant and could be distributed into several
      MDR groupings. A MDR grouping carrying pUO-StVR2, with a defined RP (AMP/bla(OXA
      30), CHL/catA1, [STR-SPT]/[strA/B,aadA1a], SUL/[sul1,sul2], TET/tet(B),
      qacEDelta1, merA, +/-TMP/dfrA12, and containing InH), was represented by 49
      isolates. The VPs of these isolates (24 genes screened) differed from that of the
      type strain LT2 by the absence of the sopE1 and pef genes. Macrorestriction
      analysis established six combined XbaI/BlnI PFGE profiles, and supported a clonal
      relationship among most of the isolates. CONCLUSIONS: During 2001-02, the
      isolates carrying pUO-StVR2 constituted the second most frequent S. Typhimurium
      MDR grouping recorded in the PA, preceded only by the pandemic pentaresistant
      DT104. Polymorphisms on the genomic DNA, different phage types, different plasmid
      profiles and the detection of trimethoprim resistance in one isolate encoded by
      an additional plasmid, were consistent with both intra-cluster evolution and
      horizontal transfer of the hybrid plasmid.

PMID- 16286361
TI  - Effect of medium type, age and aeration on the MICs of tigecycline and classical
      tetracyclines.
AB  - BACKGROUND: Tigecycline is a minocycline derivative, belonging to a chemical
      class prone to oxidation and to medium-related effects on susceptibility. We
      therefore studied the effect of medium type and age on the tigecycline MICs found
      in broth and on agar by the Clinical Laboratory Standards Institute and British
      Society for Applied Chemotherapy methods. METHODS: MICs of tigecycline,
      minocycline and tetracycline were determined for 96 non-fastidious bacteria and
      20 streptococci using Mueller-Hinton broth (MHB), Mueller-Hinton agar (MHA), Iso
      Sensitest broth (ISB) and Iso-Sensitest agar (ISA) as: (i) freshly-prepared
      media; (ii) fresh media but with the antibiotic added 1 day before inoculation
      and (iii) media stored for 7 days before antibiotic addition and use. RESULTS:
      MICs of tigecycline in fresh MHB were up to two doubling dilutions higher than on
      or in MHA, ISA or ISB. Media with tigecycline or classical tetracyclines added a
      day before use gave raised MICs, though rarely by more than one dilution. MICs of
      tigecycline (less so classical tetracyclines) were increased in 7-day-old MHB or
      ISB, even though the antibiotic was freshly added. This latter effect was
      greatest for the most susceptible strains and was absent or much reduced for
      organisms with MICs > or = 8 mg/L; it did not occur in the corresponding agar
      dilution tests. Addition of blood to MHB largely abrogated the effect, as did
      steaming the broth before adding the antibiotic. CONCLUSIONS: The raised MICs of
      tigecycline in aged broth probably reflect inactivation by dissolved oxygen. This
      accords with the lack of any MIC increase in newly-steamed (i.e. degassed) MHB or
      on aged agar (which is melted at 100 degrees C before use). Blood, which also
      abrogated the effect, may increase reducing capacity, protecting the tigecycline.
      At a practical level, broth MIC determinations for tigecycline should always
      employ fresh media.

PMID- 16286362
TI  - Intervention in a family of Boolean networks.
AB  - MOTIVATION: Intervention in a gene regulatory network is used to avoid
      undesirable states, such as those associated with a disease. Several types of
      intervention have been studied in the framework of a probabilistic Boolean
      network (PBN), which is a collection of Boolean networks in which the gene state
      vector transitions according to the rules of one of the constituent networks and
      where network choice is governed by a selection distribution. The theory of
      automatic control has been applied to find optimal strategies for manipulating
      external control variables that affect the transition probabilities to desirably
      affect dynamic evolution over a finite time horizon. In this paper we treat a
      case in which we lack the governing probability structure for Boolean network
      selection, so we simply have a family of Boolean networks, but where these
      networks possess a common attractor structure. This corresponds to the situation
      in which network construction is treated as an ill-posed inverse problem in which
      there are many Boolean networks created from the data under the constraint that
      they all possess attractor structures matching the data states, which are assumed
      to arise from sampling the steady state of the real biological network. RESULTS:
      Given a family of Boolean networks possessing a common attractor structure
      composed of singleton attractors, a control algorithm is derived by minimizing a
      composite finite-horizon cost function that is a weighted average over all the
      individual networks, the idea being that we desire a control policy that on
      average suits the networks because these are viewed as equivalent relative to the
      data. The weighting for each network at any time point is taken to be
      proportional to the instantaneous estimated probability of that network being the
      underlying network governing the state transition. The results are applied to a
      family of Boolean networks derived from gene-expression data collected in a study
      of metastatic melanoma, the intent being to devise a control strategy that
      reduces the WNT5A gene's action in affecting biological regulation. AVAILABILITY:
      The software is available on request. SUPPLEMENTARY INFORMATION: The
      supplementary Information is available at http://ee.tamu.edu/~edward/tree

PMID- 16286366
TI  - Prevalence, causes, and impact of cancer-associated thrombosis.
AB  - PURPOSE: Despite advances in the treatment of venous thromboembolism (VTE) in the
      cancer population, cancer-associated thrombosis remains a serious and potentially
      life-threatening disease. This article will review the scope and impact of cancer
      associated thrombosis, some of the possible risk factors, and current practice
      patterns. SUMMARY: Epidemiology data identify thrombosis as the second leading
      cause of mortality in cancer patients following the disease itself. The risk of
      recurrent VTE and all-cause death is 3-fold higher in patients with concurrent
      VTE and malignancy compared to non-cancer patients with VTE. It has been
      estimated that one in seven hospitalized cancer patients who die do so from a
      pulmonary embolism. Risk factors for cancer-associated thrombosis include tumor
      type, anti-tumor therapy, surgery, and immobility. Furthermore, an idiopathic VTE
      can be a predictor of occult malignancy, with one study suggesting that
      individuals who present with an unprovoked episode of VTE have a 10% frequency of
      subsequent cancer. The Fundamental Research in Oncology and Thrombosis
      (FRONTLINE) study collected data on the perceived risks and practice patterns
      with regard to VTE in cancer patients undergoing surgical and medical management
      of their malignancy. Additionally, the study provided information on
      international and regional practice patterns for the management of VTE in cancer
      patients. Respondents indicated that brain and pancreatic tumors were associated
      with an increased risk of VTE. Eight percent of respondents considered the use of
      central venous access lines to be associated with a high risk of VTE. The
      FRONTLINE study also indicated that surgeons are more likely to use
      thromboprophylaxis than medical oncologists and that low molecular weight
      heparins (LMWHs) are the most commonly used method for prevention of VTE.
      CONCLUSION: Cancer patients are at greater risk of VTE and death compared to non
      cancer patients; therefore, optimizing methods for the treatment and prevention
      of thrombosis is of particular importance in this population.

PMID- 16286363
TI  - Selecting an anticoagulant for recurrent venous thromboembolism in cancer.
AB  - PURPOSE: The thrombogenicity of newer anticancer agents and the challenges
      associated with managing cancer patients on warfarin have led to the evaluation
      of the low-molecular-weight heparins (LMWHs) for primary and secondary
      prophylaxis in this high-risk patient population. SUMMARY: The first published
      trial of LMWH in cancer compared three months of warfarin therapy with enoxaparin
      in cancer patients with proximal deep venous thrombosis (DVT), pulmonary embolism
      (PE), or both. All patients received four days of enoxaparin 1.5 mg/kg and were
      then randomized to continue receiving enoxaparin or begin warfarin therapy. Due
      to inadequate patient enrollment, no statistically significant differences were
      detected between the two treatment groups. In a similar patient population, the
      Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for
      the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT)
      trial evaluated the use of long-term dalteparin for the prevention of recurrent
      venous thromboembolism (VTE) in patients with cancer. Cancer patients with
      proximal DVT, PE, or both were randomized to initial treatment with dalteparin
      followed by either six months of oral anticoagulant therapy or dalteparin
      monotherapy. The primary outcome was symptomatic, recurrent VTE, and secondary
      outcomes were bleeding events and survival time. The cumulative risk of recurrent
      VTE at six months was reduced from 17% in the oral anticoagulant group to 9% in
      the dalteparin group, a risk reduction of 52% (p=0.002). No significant
      differences in bleeding events or overall mortality occurred between the groups.
      Recent recommendations from the American College of Chest Physicians on the
      treatment of cancer-associated thrombosis are based in part on data from the CLOT
      trial and support the use of dalteparin and tinzaparin in the long-term treatment
      of patients with DVT and cancer. Finally, results of recent trials support the
      concept that antithrombotic therapy with dalteparin or nadroparin may have an
      antineoplastic effect, resulting in improved survival time. However, these
      results require further validation. CONCLUSION: Despite the absence of oncology
      specific guidelines for cancer-associated thrombosis, pharmacists now have a
      number of new tools available for selecting an anticoagulant, including results
      from several clinical trials with LMWHs and recent reports from national
      meetings.

PMID- 16286367
TI  - Considerations and challenges with existing treatments for thrombosis in cancer
      patients.
AB  - PURPOSE: One of the standard treatments for cancer-associated thrombosis has been
      initial therapy with unfractionated heparin (UFH) followed by long-term therapy
      with an oral anticoagulant (i.e., warfarin). However, characteristics associated
      with these two agents may make them suboptimal for many cancer patients. This
      article will explore some of the considerations and limitations when using UFH
      and warfarin in the cancer population and will also utilize case studies to
      emphasize the importance of individualized care. SUMMARY: UFH is an effective
      anticoagulant when doses are adjusted to maintain the activated partial
      thromboplastin time (aPTT) within a specified therapeutic range. However, due to
      the complex pharmacokinetics of this agent, patients must undergo frequent
      monitoring to maintain a therapeutic aPTT. In addition, UFH can be associated
      with serious adverse events including osteoporosis, heparin-induced
      thrombocytopenia, and bleeding. Similar to UFH, warfarin requires frequent
      monitoring and dose adjustments to maintain the International Normalized Ratio
      (INR) within the therapeutic range of 2.0 to 3.0. Warfarin also has numerous drug
      herbal, drug-food, and drug-drug interactions, including interactions with many
      commonly used anti-tumor therapies. Complications related to UFH and warfarin in
      the treatment of cancer-associated thrombosis have gradually been minimized with
      the increased use of low molecular weight heparins (LMWHs), which are associated
      with reduced incidence of bleeding, heparin-induced thrombocytopenia, and drug
      interactions. In addition, LMWHs allow for convenient daily dosing without
      requiring routine monitoring and the option of home therapy. CONCLUSION: When
      deciding on the optimal anticoagulant strategy, pharmacists must take into
      account the unique characteristics and needs of each individual patient as well
      as the specifics of the various anticoagulant therapies. Future strategies for
      the initial and long-term treatment of cancer-associated thrombosis may
      increasingly incorporate LMWHs because of factors related to safety and
      convenience.

PMID- 16286369
TI  - Autumnal thoughts.

PMID- 16286370
TI  - Venous ulcers: the benefits of superficial venous surgery should not be
      overlooked.

PMID- 16286371
TI  - Evaluation of wound healing activity of Vanda roxburghii R.Br(Orchidacea): a
      preclinical study in a rat model.
AB  - The extract of Vanda roxburghii was administered topically to rats at a dose of
      150mgkg(-1) day(- 1) for 10 days and was studied for its effect on wound healing,
      using the excision wound model. A 60% reduction in wound diameter was observed in
      the test group rats receiving the extract compared to controls (48%). Significant
      increases in wet and dry granulation tissue weights (P < .001), hydroxyproline (P
      < .001), and hexosamine (P < .003) contents were detected. An increase in protein
      content was also detected in the test group (P > .05, ns). These findings are
      consistent with wound healing at cellular levels. The pro-healing action may be
      attributed either to increased collagen deposition or to better alignment and
      maturation or both. The test wounds (extract-treated wounds) were, on average,
      fully healed by the 13th day, whereas the control group healed, on average, by
      the 20th day. These data suggest that the extract of Vanda roxburghii
      administered topically has wound-healing potential in rats.

PMID- 16286372
TI  - Turmeric (Curcuma longa) rhizome paste and honey show similar wound healing
      potential: a preclinical study in rabbits.
AB  - The potential efficacy of fresh turmeric (Curcuma longa) paste to heal wounds was
      tested in a preclinical study in an animal model. Turmeric paste was compared
      with honey as a topical medicament against a control on experimentally created
      full-thickness circular wounds in 18 rabbits (Oryctolagous cuniculus). Wound
      healing was assessed on the basis of physical, histomorphological, and
      histochemical parameters on treatment days 0, 3, 7, and 14. Only tensile strength
      was measured on day 14 of treatment. It was observed that the wound healing was
      statistically significantly faster (P < .01) in both treatment groups compared to
      the control group.

PMID- 16286373
TI  - Some effects of a topical collagen-based matrix on the microcirculation and wound
      healing in patients with chronic venous leg ulcers: preliminary observations.
AB  - The microcirculation of the wound bed is a key parameter for improving
      granulation tissue formation and, hence, wound healing. The aim of this study was
      to determine whether a wound dressing comprising collagen/oxidized regenerated
      cellulose has effects over a short term on wound healing. Wounds were evaluated
      using a clinical wound score; pain associated with wounds was measured using a
      visual analogue scale. Wound microcirculation was evaluated using a technique
      based on noncontact remission spectroscopy. A prospective trial was performed in
      40 patients with chronic venous leg ulcers (mean age 74 years; range, 43-93
      years; 25 females and 15 males). Patients in group A were treated with PROMOGRAN
      Matrix (Johnson& Johnson, New Brunswick, NJ) combined with "good" ulcer care for
      2 weeks. Control group B consisted of 10 patients who received only good ulcer
      care. The authors measured a favorable clinical response in 76.9% (group A)
      versus 66.7% (group B). The mean reduction of ulcer area was statistically
      significant in group A (P < .05). The wound score improved in group A from 2.28
      +/- 1.24 (before treatment) increasing to 3.72 +/- 1.57 (after 1 week; P <
      .00023) and 4.92 +/- 1.68 (after 2 weeks; P < .000027). In group B, the score
      improved from 1.44 +/- 1.33 (before treatment) to 3.22 +/- 1.30 (after 1 week; P
      < .0077). The mean visual analogue pain score before treatment was 8.72 (group A)
      and 7.88 (group B) (ns, P > .05). After 1 week of treatment, the score dropped to
      5.76 (group A) and 6.66 (group B). In the second week, group A patients had a
      mean pain score of 3.84 compared with the pain score before treatment (P < .05).
      After 1 week of treatment, in group A there was a decrease in remission
      spectroscopy, which is considered to reflect an improvement in microcirculation.

PMID- 16286368
TI  - In vitro selection, characterization, and application of deoxyribozymes that
      cleave RNA.
AB  - Over the last decade, many catalytically active DNA molecules (deoxyribozymes;
      DNA enzymes) have been identified by in vitro selection from random-sequence DNA
      pools. This article focuses on deoxyribozymes that cleave RNA substrates. The
      first DNA enzyme was reported in 1994 and cleaves an RNA linkage. Since that
      time, many other RNA-cleaving deoxyribozymes have been identified. Most but not
      all of these deoxyribozymes require a divalent metal ion cofactor such as Mg2+ to
      catalyze attack by a specific RNA 2'-hydroxyl group on the adjacent
      phosphodiester linkage, forming a 2',3'-cyclic phosphate and a 5'-hydroxyl group.
      Several deoxyribozymes that cleave RNA have utility for in vitro RNA
      biochemistry. Some DNA enzymes have been applied in vivo to degrade mRNAs, and
      others have been engineered into sensors. The practical impact of RNA-cleaving
      deoxyribozymes should continue to increase as additional applications are
      developed.

PMID- 16286374
TI  - A prospective multicenter study of the efficacy and tolerability of cryopreserved
      allogenic human keratinocytes to treat venous leg ulcers.
AB  - Allogeneic human keratinocyte cultures have been used to treat burn wounds, donor
      sites, and chronic skin ulcers with some success. Cryopreservation of these
      cultures allows for the production of large standardized batches that are readily
      available for use. The aim of the study presented in this report was to study
      effects of cryopreserved cultured allogenic human keratinocytes (CryoCeal) on
      chronic lower extremity wounds. Parameters were measured to study efficacy,
      tolerability, pain associated with chronic wounds, and quality of life of
      patients. Twenty-seven patients with hard-to-heal venous leg ulcers received a
      maximum of 9 applications of CryoCeal in a prospective, uncontrolled multicenter
      study lasting 48 weeks. Eleven out of 27 patients (41%; 95% CI: 22%-61%) had
      complete wound closure within 24 weeks (1 week). The time required for complete
      wound closure in these 11 patients ranged from 4.1 to 24.9 weeks. Only 1 patient
      had recurrence of the ulcer at 48 weeks. Local (wound) pain scores decreased from
      a mean of 2.5 at baseline to 0.9 at week 24. Fifty percent of the patients
      attained a pain score of 0 after 12 weeks and remained stable at this score until
      the end of the study. Overall, the patient quality of life was better at week 24,
      compared to baseline values. The treatment was well tolerated, and wound
      infection was the most frequently occurring adverse event.

PMID- 16286375
TI  - Current state and perspective on medical treatment of critical leg ischemia: gene
      and cell therapy.
AB  - Critical limb ischemia (CLI) is a severe disease associated with a high risk of
      amputation and mortality. In patients who cannot be revascularized, several
      medical options have been tested, including the use of prostanoids, spinal cord
      stimulation, and lumbar sympathectomy. None of these treatments has demonstrated
      a benefit on the amputation rates after 6 months of follow-up; these treatments
      cannot therefore be recommended for CLI treatment in patients for whom surgery is
      not an option. In this setting, gene therapy and cell therapy to stimulate
      angiogenesis have been tested mainly in phase I and II clinical trials and are
      reviewed in this article. These studies demonstrated the short-term safety and
      feasibility of these new approaches, but larger randomized studies remain
      necessary to demonstrate their clinical benefits and longterm safety.

PMID- 16286376
TI  - Wound problems in surgery for talipes equinovarus.
AB  - The traditional treatment for talipes equinovarus (TEV) has been open surgery in
      many units around the world. The complication rates for primary corrective
      surgery are relatively small but may affect outcome significantly. The
      complications of surgery in relapsed TEV are more frequent than for primary
      surgery, and problems relating to wound healing present difficult challenges to
      the treating surgeon. An overview of the approaches to management of this still
      challenging condition are presented, and the factors involved in wound healing
      problems and strategies for their prevention and treatment are presented. In
      particular, the belated but rapid spread worldwide of the Ponseti nonoperative
      approach to treating talipes is the most important factor in reducing the rates
      of surgery and therefore the complications that may ensue.

PMID- 16286377
TI  - Venous insufficiency due to chronic traumatic arteriovenous fistula: two case
      reports.
AB  - Chronic traumatic arteriovenous fistula (AVF) is a rare complication of vascular
      injury, and few papers have reported on its consequences to the venous system,
      that is, venous insufficiency. The author has highlighted this problem with 2
      case reports in this case presentation. One patient had recurrent chronic ulcer
      of the left foot. The other patient developed deep vein thrombosis following
      repair to the large AVF of the right thigh.

PMID- 16286378
TI  - A verrucous carcinoma of the foot on an injection site: a case report.
AB  - Verrucous carcinoma of the foot, also known as epithelioma cuniculatum, usually
      occurs on the inner aspect of the foot. It is a slow-growing variant of squamous
      cell cancer with a low metastatic potential. This case report presents a patient
      with a verrucous carcinoma of the foot who had been receiving long-term
      intralesional triamcinolone acetonide in that site for some steroid-responsive
      dermatosis, presumably lichen simplex chronicus.

PMID- 16286379
TI  - The significance of medial sural artery integrity in popliteal artery trauma: a
      case report.
AB  - Two patients with popliteal artery trauma who underwent secondary amputations due
      to refractory calf sepsis despite a patent arterial repair are presented in this
      case report. The medial sural artery, the main arterial supply of the medial head
      of the gastrocnemius, was surgically severed in both patients owing to the use of
      a continuous medial incision from the supra level to infragenicular level. The
      compromised arterial supply of the medial head of the gastrocnemius muscle may
      have contributed to the devitalization of the muscle and the subsequent calf
      sepsis, and it is speculated that this was related to the unfavorable outcome.

PMID- 16286383
TI  - Oh #*$%#! Another pesky incidental thyroid nodule!

PMID- 16286384
TI  - Radiologic morphology of low-grade primary central nervous system lymphoma in
      immunocompetent patients.
AB  - BACKGROUND AND PURPOSE: Primary central nervous system lymphomas (PCNSLs) are
      usually high-grade and are rarely low-grade non-Hodgkin lymphomas (NHLs). On MR
      imaging, PCNSLs typically present as contrast-enhancing lesions in contact with
      the subarachnoid space without evidence of necrosis. We evaluated the radiologic
      morphology and clinical characteristics of low-grade PCNSLs, hypothesizing that
      they may differ from high-grade PCNSLs. METHODS: Records were reviewed from 332
      patients screened for inclusion in 3 multicenter prospective trials. MR imaging
      scans were obtained from all patients and were centrally reviewed by 2 consultant
      neuroradiologists. RESULTS: Ten patients (3%) with low-grade PCNSLs (7 men and 3
      women; median age, 59 years; age range, 19-61 years) were identified. Four
      patients had one lesion, 2 patients 2 lesions, and 4 patients had multiple
      lesions. The following radiologic features infrequently seen in high-grade PCNSLs
      were found in a substantial proportion of patients: location in deep structures
      or spine (n = 6); lack of periventricular location (n = 5); hyperintensity on T2
      weighted images (n = 10); moderate or absent contrast enhancement (n = 6); and
      heterogeneous contrast enhancement (n = 5). In 8 patients, >2 of these features
      were present in at least one lesion, and, thus, the radiologic appearance was
      assessed atypical of high-grade PCNSLs. The atypical radiologic appearance in
      combination with atypical or mild symptoms resulted in a false or delayed
      diagnosis. CONCLUSION: Low-grade PCNSLs may have a variable and atypical
      radiologic morphology compared with high-grade PCNSLs with the risk of false or
      delayed diagnosis.

PMID- 16286385
TI  - Is volume transfer coefficient (K(trans)) related to histologic grade in human
      gliomas?
AB  - PURPOSE: The purpose of this study was to examine the relationship between
      contrast transfer coefficient [K(trans)] and grade in gliomas. MATERIAL AND
      METHODS: Median values of K(trans), CBV(T1), and of the 95th percentile (95%) of
      the distribution (K(trans) [95%] and CBV(T1) [95%]) were calculated in 39
      patients with glioma. Group comparisons and post hoc pairwise comparisons were
      performed. The relationship between variables and grade used Spearman rho and
      canonical discriminant analysis. The separation of high- from low-grade tumors
      was separately assessed by using Mann-Whitney U tests and logistic regression.
      Receiver operator curve analysis was performed for high- and low-grade tumors and
      grade III and grade IV tumors. RESULTS: There were significant differences
      between grades for all variables (P < .001). Pairwise comparisons demonstrated
      significant differences between grades II and III and II and IV for all variables
      except K(trans), which did not show significance in the grade II and III
      comparison, and between III and IV for CBV(T1) and CBV(T1) (95%; P < .01). All
      variables correlated with grade (P < .01). Discriminant analysis showed
      independent relation between both CBV(T1) and K(trans) (95%) and grade, and the
      canonical function produced a total correct classification of 74.4% of cases.
      Logistic regression analysis for low- versus high-grade tumors showed K(trans)
      (95%) and CBV(T1) to be independent factors (P < .01 and P < .05). CONCLUSION:
      There are strong independent relationships between both CBV and K(trans) and
      histologic grade in gliomas. Both measurements show good discriminative power in
      distinguishing between low- and high-grade tumors with diagnostic sensitivity and
      specificity >90%.

PMID- 16286386
TI  - MR imaging correlates of survival in patients with high-grade gliomas.
AB  - BACKGROUND AND PURPOSE: For patients with malignant gliomas, clinical data
      including age, perioperative Karnofsky Performance Status (KPS), and tumor
      resection-and tumor imaging features-including necrosis and edema-have been found
      to correlate with survival. The purpose of this study was to assess the validity
      of these results and determine whether other imaging features are useful in
      predicting survival. METHODS: We analyzed the relationship between 15 imaging
      variables obtained from contrast-enhanced MR imaging scans and survival in
      patients with grade III (n = 43) and grade IV (n = 110) glioblastoma multiforme
      (GBM) gliomas. Image analysis was performed by 2 neuroradiologists who were
      blinded to clinical data. The Kaplan-Meier method was used to estimate survival
      probabilities. Univariable Cox models were used to assess the impact of imaging
      features on survival. A recursive partitioning analysis also was performed.
      RESULTS: As expected, age and KPS scores had significant prognostic value for
      both tumor grades. The extent of resection was not a statistically meaningful
      predictor of survival. For GBM, univariable analysis revealed the following
      imaging features to be significant, (hazard ratios in parentheses): noncontrast
      enhancing tumor (nCET, 0.55), edema (1.62), satellites (1.74), and multifocality
      (4.34). For grade III tumors, the Cox hazard ratio for necrosis was 4.43 (P =
      .014) and correlated with a poor outcome and survival rates comparable to GBM
      patients. Lack of nCET, multifocality, and satellite lesions also were correlated
      with shortened survival. CONCLUSION: Of 15 tumor imaging features in GBM
      patients, only nCET, edema, and multifocality/satellites are statistically
      significant prognostic indicators. The survival advantage of nCET is a novel
      finding.

PMID- 16286387
TI  - The effect of corticosteroid medication on quantitative MR parameters of the
      brain.
AB  - BACKGROUND AND PURPOSE: Quantitative MR imaging techniques such as magnetization
      transfer imaging (MTI), diffusion-weighted imaging (DWI), and MR spectroscopy are
      promising diagnostic tools for use with patients with diffuse brain diseases such
      as neuropsychiatric systemic lupus erythematosus (NPSLE). Such patients are often
      on corticosteroid (CS) treatment. Presently, it is unknown whether CSs per se
      influence quantitative MR imaging measurements. The aim of this study was to
      evaluate the effect of low-dose oral CSs on MTI, DWI, and MR spectroscopy
      parameters of the brain. METHODS: Twenty-seven rheumatoid arthritis (RA) patients
      with and without CS medication and 15 healthy controls were subjected to
      conventional MR imaging, whole-brain MTI and DWI, and single-voxel MR
      spectroscopy. Oral CSs were used by 13 of the RA patients. Univariate analyses
      with age as a covariate were performed on MTI, DWI, and MR spectroscopy
      parameters between RA patients with and without CSs and healthy controls. Pearson
      correlations were calculated between all imaging parameters and duration of
      disease, duration of CS use, and CS dosage. RESULTS: No significant differences
      between the groups of subjects or significant correlations with clinical
      parameters were found for MTI, DWI and MR spectroscopy parameters. CONCLUSION: In
      this study, we found no evidence for an effect of low-dose oral CSs on whole
      brain MTI and DWI histogram parameters and single-voxel MR spectroscopy
      measurements of the brain. The results of this study demonstrate that it is
      unlikely that MTI, DWI, and MR spectroscopy parameters reported in NPSLE studies
      are confounded by low-dose oral CS.

PMID- 16286388
TI  - The spatial distribution of MR imaging abnormalities in cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their
      relationship to age and clinical features.
AB  - BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) is a condition causing recurrent
      subcortical strokes. MR imaging, which shows focal lacunar infarcts and
      leukoaraiosis, plays a central role in the diagnosis and evaluation. We studied
      MR imaging abnormalities in a large prospectively recruited cohort of CADASIL
      patients to describe the spatial distribution of abnormalities, determine how
      this distribution alters with age, and identify any correlations with the
      clinical features of the disease. METHODS: In this study, 112 CADASIL subjects
      from 64 families were prospectively recruited. MR imaging scans were graded by a
      single neuroradiologist, by using the modified Scheltens scale, to quantify the
      severity of high-signal-intensity changes in different brain regions. RESULTS:
      Lesion load increased progressively with age. Scores were maximal in the frontal,
      parietal, and anterior temporal cortex, and the external capsule; intermediate in
      the pons; and relatively low in the corpus callosum, caudate, globus pallidus,
      cerebellum, midbrain, and medulla. Anterior temporal pole involvement was common
      at all ages and, when present, usually confluent, but this was absent in 33% of
      patients 20-29 years of age. A history of stroke correlated with total Scheltens
      score and internal capsule and pontine scores. Dementia correlated with total
      Scheltens score and subcortical white matter score, whereas depression correlated
      with subcortical white matter score but not total Scheltens score. CONCLUSIONS:
      There is a characteristic pattern of MR imaging abnormalities in CADASIL that
      aids in differential diagnosis; however, some characteristic features, such as
      anterior temporal pole involvement, can be absent. MR imaging lesion load
      correlated with some clinical features including stroke and dementia, whereas
      depression is more common in individuals with deep white matter changes.

PMID- 16286389
TI  - Multiple sclerosis and Alzheimer disease through the looking glass of MR imaging.

PMID- 16286390
TI  - Differences in functional MR imaging activation patterns associated with
      confrontation naming and responsive naming.
AB  - BACKGROUND AND PURPOSE: Direct cortical stimulation studies suggest that
      responsive naming is more widely distributed within the temporal lobe than
      confrontation naming and involves anterior temporal regions typically resected in
      a standard temporal lobectomy. The aim of the current study was to further
      demonstrate the anatomic dissociation between confrontation and responsive naming
      by using functional MR imaging (fMRI). METHODS: Twenty participants underwent
      fMRI while performing either a confrontation or responsive naming task. Regions
      of interest were identified within the anterior and posterior temporal lobe.
      RESULTS: Responsive naming produced more activation than confrontation naming
      within the dominant temporal lobe, with activation extending into the temporal
      pole. Activation in the dominant temporal lobe associated with responsive naming
      was observed in the superior, middle, and inferior temporal gyri but was limited
      to the middle temporal gyrus for confrontation naming. Although both naming tasks
      produced activation within the posterior temporal region of interest in all
      participants, responsive and confrontation naming produced activation within the
      anterior temporal region of interest in 90% versus 60% of the sample,
      respectively. Areas of the dominant hemisphere activated by both tasks included
      parts of the middle occipital and middle temporal gyri, inferior frontal lobe,
      and hippocampus, among others. CONCLUSION: Findings are consistent with cortical
      stimulation studies and suggest that responsive naming produces more widespread
      activation within the temporal lobe compared with confrontation naming. The
      activation more often included anterior temporal regions during responsive naming
      as compared with confrontation naming. In clinical cases where the functional
      assessment of the temporal lobe-particularly the anterior regions-is important,
      the current results suggest responsive naming should be a useful fMRI paradigm
      and may ultimately help predict the risk of postsurgical language changes.

PMID- 16286391
TI  - MR imaging findings of intracranial dural arteriovenous fistulas: relations with
      venous drainage patterns.
AB  - BACKGROUND AND PURPOSE: Venous drainage patterns are a major determinant of
      clinical outcome in intracranial dural arteriovenous fistula (DAVF) patients. In
      this study, we sought to identify MR imaging finding differences between DAVF
      types classified on the basis of venous drainage patterns. METHODS: Twenty-seven
      patients diagnosed as having DAVFs by conventional angiography were included.
      Medical records (n = 27), and MR imaging (n = 27) and MR angiography (MRA; n =
      11) findings were retrospectively reviewed. MR imaging findings included flow
      void cluster, engorged ophthalmic vein/proptosis, white matter hyperintensity,
      intracranial hemorrhage, dilated leptomeningeal or medullary vessels, venous
      pouch, and leptomeningeal or medullary vascular enhancements. MRA findings
      included identifiable fistula, venous flow-related enhancement, and prominent
      extracranial vessels. Patients' presentations and MR imaging findings were
      compared among angiographic type I, II, and III cases (according to Borden's
      classification), and MRA findings were compared between cases with and without
      retrograde leptomeningeal venous drainage (RLVD). RESULTS: Patient presentations
      were aggressive in one (13%) of the type I cases, 5 (50%) of the type II cases,
      and 8 (100%) of the type III cases (P = .002). Aggressive presentations included
      hemorrhage, focal neurologic deficits, seizures, intracranial hypertension, and
      an altered mental status. MR images showed significantly higher frequencies of
      dilated leptomeningeal or medullary vessels in a higher type [0 in type I, 5
      (42%) in type II, and 7 (100%) in type III], and of leptomeningeal or medullary
      vascular enhancements [0 in type I, 4 (33%) in type II, and 7 (100%) in type
      III]. By using MRA, fistulas were identified only in cases with RLVD (5 [83%]).
      Venous flow-related enhancement was present in 10 cases (91%). A sole false
      negative case on MRA, as compared with conventional angiography, resulted from
      nonvisualization of the slow venous flow (8%). No false-positive fistula was
      found at the other intracranial sites in all cases. Overall, MRA assessment for
      DAVF was adequate for both fistula and venous flow-related enhancement in 10
      cases (91%) and inadequate in a remaining case because of the fistular location
      out of field. CONCLUSION: MR imaging demonstration of leptomeningeal or medullary
      vascular dilation and enhancements may be associated with features that are
      considered predictors of a poor outcome and indicates a need for urgent therapy
      in intracranial dural AVF patients. MRA is a complementary tool for the
      identification of dural AVF with venous flow-related enhancement.

PMID- 16286392
TI  - Surface appearance of the vertebrobasilar artery revealed on basiparallel
      anatomic scanning (BPAS)-MR imaging: its role for brain MR examination.
AB  - PURPOSE: Basiparallel anatomic scanning (BPAS)-MR imaging is a simple MR imaging
      technique that we designed for visualization of the surface appearance of the
      vertebrobasilar artery within the cistern. It can clearly show the outer contour
      of occluded arteries or thrombosed aneurysms. By comparing BPAS-MR imaging with
      3D time-of-flight (TOF) MR angiography (MRA), we can precisely evaluate the
      vertebrobasilar artery condition. The purpose of this study is to determine the
      value of BPAS-MR imaging for brain MR examination. MATERIALS AND METHODS: We
      obtained BPAS-MR imaging, in addition to 3D TOF MRA, for 385 consecutive patients
      who underwent brain MR imaging and MRA in our hospital between April 1 and August
      31, 2003. Their complaints varied from mild head symptoms to severe neurologic
      illness. Comparing BPAS-MR imaging with MRA, we revealed the character of BPAS-MR
      imaging and determined the role and value of displaying vascular outer contour.
      RESULTS: Although the cases did not represent a restricted group of
      vertebrobasilar diseases, BPAS-MR imaging contributed to accurate evaluation of
      the vertebrobasilar artery in 90 of our 385 patients (23.4%). Of particular note,
      16.1% of our patients could not be evaluated accurately by MRA only. BPAS-MR
      imaging was useful to confirm hypoplastic or occluded vertebral arteries and to
      reveal the whole appearance of large or partially thrombosed aneurysms of the
      vertebrobasilar system. CONCLUSION: The combination of the BPAS-MR imaging and
      the 3D TOF MRA was necessary for accurate diagnosis in 16.1% of our ordinary
      patients. We should evaluate not only MRA but also the vascular outer contour
      revealed on BPAS-MR imaging, though its application is limited to the
      vertebrobasilar system and the screening use.

PMID- 16286393
TI  - Functional analysis of third ventriculostomy patency by quantification of CSF
      stroke volume by using cine phase-contrast MR imaging.
AB  - OBJECTIVE: Endoscopic third ventriculostomy (ETV) is increasingly used as
      alternative treatment for obstructive hydrocephalus. The aim of this study was to
      determine the utility of quantitative and qualitative examinations with cine
      phase-contrast MR imaging to determine the efficacy of ventriculostomy across
      time and whether CSF pulsation is restored after ETV. METHODS: Thirty-eight
      patients treated with ETV were evaluated with cine phase-contrast MR within 1
      month after surgery. Follow-up studies were performed after 1 year in 25 patients
      and after 2 years in 12. We evaluated flow void changes in the floor of the third
      ventricle and quantified the stroke volume at the site of the ventriculostomy. We
      also recorded changes in ventricular size and clinical outcome. To determine the
      restoration of CSF pulsation, we compared the CSF waveform at the ventriculostomy
      with the CSF waveform at the aqueduct in a healthy control group. RESULTS: After
      ventriculostomy, restoration of pulsate motion characteristics of CSF circulation
      was observed. The stroke volume registered at ventriculostomy was maintained with
      time. There was a statistically significant relationship between clinical outcome
      and stroke volume. Overall flow magnitude was the most effective variable to
      determine which patients would improve after surgery. Values >75 mm3 showed a
      sensitivity of 76.7% and a specificity of 87.5% There was no relationship between
      ventricular size changes and clinical outcome. Patients with primary aqueduct
      stenosis had the best response to surgery, whereas patients with Arnold Chiari
      malformation or communicating hydrocephalus had the worst response. CONCLUSION:
      Quantitative analysis with phase-contrast MR imaging indicates that ETV is an
      efficient technique for restoring CSF pulsation, with efficacy being maintained
      during the follow-up controls. Quantification of stroke volume at ventriculostomy
      is a good indicator of the functional status of ETV, and a high stroke volume in
      the ventriculostomy appears to be a positive predictor of favorable clinical
      outcome.

PMID- 16286394
TI  - Unusual presentation of central nervous system cryptococcal infection in an
      immunocompetent patient.
AB  - The imaging findings of cryptococcosis affecting the brain in immunocompetent
      patients can be different from the more commonly described findings in
      immunocompromised patients. We report a case of an extremely unusual MR
      appearance of central nervous system cryptococcosis in a 49-year-old
      immunocompetent man.

PMID- 16286395
TI  - Evaluation of regional cerebral blood flow in fahr disease with schizophrenia
      like psychosis: a case report.
AB  - We report the case of a patient with Fahr disease presenting with schizophrenia
      like psychosis for whom a technetium Tc99 methyl cysteinate dimmer brain study
      was used to evaluate regional blood flow. A brain single photon-emission CT study
      showed increased cerebral blood flow to the bilateral temporal lobes. Such
      perfusion abnormalities may reflect psychotic symptoms, including auditory
      hallucinations and delusions, which suggests a disruption of the cortico
      subcortical neural circuits in psychosis.

PMID- 16286396
TI  - Spontaneous resolution of traumatic pseudoaneurysm of the middle meningeal
      artery.
AB  - We describe a case of traumatic pseudoaneurysm of the middle meningeal artery in
      a patient after a head trauma. The aneurysm was found incidentally and resolved
      spontaneously without any intervention; this outcome suggests that middle
      meningeal artery aneurysm may not require treatment in all cases and can be
      followed conservatively with follow-up conventional angiography.

PMID- 16286397
TI  - Unique anomalous origin of the left anterior cerebral artery.
AB  - We present the case of an anomalous origin of the left anterior cerebral artery
      (ACA) from the supraclinoid segment of the right internal carotid artery. Because
      of improved imaging quality, anomalies of the ACA-anterior communicating artery
      (AComA) complex are increasingly recognized on transaxial images. Although most
      of these anomalies are incidental findings of little clinical significance, some
      ACA-AComA complex anomalies are clinically significant. Recognition of these
      anomalies may be instrumental in developing a differential diagnosis or for
      improved surgical planning.

PMID- 16286398
TI  - Volumetric perfusion CT using prototype 256-detector row CT scanner: preliminary
      study with healthy porcine model.
AB  - This is a preliminary demonstration of volumetric perfusion CT of the brain in
      domestic pigs by using a prototype 256-detector row CT. Scan range is
      approximately 100 mm in the craniocaudal direction with 0.5-mm section thickness.
      The 256-detector row CT is an easily available imaging technique that can provide
      volumetric cine imaging, CT angiography, and perfusion CT in a wide craniocaudal
      coverage simultaneously.

PMID- 16286399
TI  - Late rebleeding of ruptured intracranial aneurysms treated with detachable coils.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to assess the incidence of
      late rebleeding of ruptured intracranial aneurysms treated with detachable coils.
      PATIENTS AND METHODS: A clinical follow-up study was conducted in 393 consecutive
      patients with a ruptured aneurysm treated with detachable coils between January
      1995 and January 2003. Late rebleeding was defined as recurrent hemorrhage from a
      coiled aneurysm >1 month after coiling. One patient was lost to follow-up. Total
      clinical follow-up of the 392 patients who were coiled for ruptured cerebral
      aneurysms was 18,708 months (1559 patient years; median, 48 months; mean, 47.7
      months; range, 0-120 months). RESULTS: Four patients suffered late rebleeding
      from the coiled aneurysm at 8, 12, 30, and 40 months after coiling, respectively.
      Two of these patients died. Another patient died of probable rebleeding 4 months
      after coiling. The incidence of late rebleeding was 1.27% (5/393) and mortality
      of late rebleeding was 0.76% (3/393). The annual late rebleeding rate was 0.32%,
      and the annual mortality rate from late rebleeding was 0.19%. During the follow
      up period, 53 coiled aneurysms in 53 patients (13%) were additionally treated: 35
      aneurysms (8.9%) were additionally treated with coils, 16 aneurysms (4.1%) were
      additionally clipped, and 2 aneurysms (0.5%) were additionally treated with
      parent vessel balloon occlusion. CONCLUSION: The late rebleeding rate after
      coiling of ruptured cerebral aneurysms is very low. Follow-up of patients with a
      coiled aneurysm is mandatory to identify aneurysms that need additional treatment
      after reopening.

PMID- 16286400
TI  - Characterization of cerebral aneurysms for assessing risk of rupture by using
      patient-specific computational hemodynamics models.
AB  - BACKGROUND AND PURPOSE: Hemodynamic factors are thought to play an important role
      in the initiation, growth, and rupture of cerebral aneurysms. This report
      describes a pilot clinical study of the association between intra-aneurysmal
      hemodynamic characteristics from computational fluid dynamic models and the
      rupture of cerebral aneurysms. METHODS: A total of 62 patient-specific models of
      cerebral aneurysms were constructed from 3D angiography images. Computational
      fluid dynamics simulations were performed under pulsatile flow conditions
      measured on a normal subject. The aneurysms were classified into different
      categories, depending on the complexity and stability of the flow pattern, the
      location and size of the flow impingement region, and the size of the inflow jet.
      The 62 models consisted of 25 ruptured and 34 unruptured aneurysms and 3 cases
      with unknown histories of hemorrhage. The hemodynamic features were analyzed for
      associations with history of rupture. RESULTS: A large variety of flow patterns
      was observed: 72% of ruptured aneurysms had complex or unstable flow patterns,
      80% had small impingement regions, and 76% had small jet sizes. By contrast,
      unruptured aneurysms accounted for 73%, 82%, and 75% of aneurysms with simple
      stable flow patterns, large impingement regions, and large jet sizes,
      respectively. Aneurysms with small impingement sizes were 6.3 times more likely
      to have experienced rupture than those with large impingement sizes (P = .01).
      CONCLUSIONS: Image-based patient-specific numeric models can be constructed in an
      efficient manner that allows clinical studies of intra-aneurysmal hemodynamics. A
      simple flow characterization system was proposed, and interesting trends in the
      association between hemodynamic features and aneurysmal rupture were found.
      Simple stable patterns, large impingement regions, and jet sizes were more
      commonly seen with unruptured aneurysms. By contrast, ruptured aneurysms were
      more likely to have disturbed flow patterns, small impingement regions, and
      narrow jets.

PMID- 16286401
TI  - Histopathologic and immunohistochemical comparison of human, rabbit, and swine
      aneurysms embolized with platinum coils.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to clarify the cellular
      mechanisms of aneurysmal healing by comparing histologic and immunohistochemical
      findings in experimental rabbit and swine aneurysms to a human aneurysm embolized
      with platinum coils. METHODS: Swine sidewall aneurysms (n = 5, harvested at 12
      weeks) and elastase-induced rabbit aneurysms (n = 6, harvested at 24 weeks) were
      created and embolized. A single human aneurysm, embolized 6 years before death,
      was harvested following autopsy. All specimens were processed by using a modified
      paraffin embedding technique. Tissue was sectioned and stained with hematoxylin
      and eosin and Masson trichrome. Immunohistochemistry and immunofluorescence were
      performed with multiple antibodies, including alpha smooth muscle actin, myosin
      heavy chain, desmin, vimentin, and CD31. RESULTS: The human aneurysm's dome was
      filled with loose, hypocellular, amorphous tissue. The aneurysm's neck was
      completely covered with a thin layer of hypocellular tissue. Collagen and
      myofibroblasts were sparse in both the dome and neck. Rabbit aneurysms' domes
      were also filled with a loose, hypocellular tissue, amorphous matrix. In 5 of 6
      aneurysms, a thin layer of hypocellular tissue ran along the neck. Collagen and
      myofibroblasts were sparse in the dome. Swine aneurysms were filled with densely
      infiltrated tissue, including chronic inflammatory tissue and extensive,
      attenuated collagen fiber bundles associated with myofibroblasts. Thick layers of
      myofibroblasts entirely bridged the necks. CONCLUSIONS: Absence of collagen
      deposition and scant myofibroblastic reaction to platinum coil embolization are
      seen in the rabbit model but not in swine aneurysms. The elastase-induced
      aneurysm model in rabbits is more suitable than sidewall swine aneurysms for
      testing of modified devices aimed at improving intra-aneurysmal fibrosis.

PMID- 16286402
TI  - Volume measurement of intracranial aneurysms from 3D rotational angiography:
      improvement of accuracy by gradient edge detection.
AB  - Manual volume measurement of intracranial aneurysms from 3D rotational
      angiography varies on different threshold settings and, therefore, is operator
      dependent. We developed and validated a method based on automatic gradient edge
      detection that is independent on threshold settings and provides an accurate and
      reproducible volume measurement. This method was compared with manual volume
      calculation in 13 aneurysm phantoms, and the results were significantly more
      accurate.

PMID- 16286403
TI  - Preliminary experience with Leo self-expanding stent for the treatment of
      intracranial aneurysms.
AB  - We report initial experience with the use of a new intracranial stent, the Leo
      microstent in combination with detachable coils in treatment of patients with
      wide-necked cerebral aneurysms. The Leo stent represents a significant advance in
      the vascular treatment of intracranial aneurysm with high radial force and an
      easy delivery system. It is a feasible, secure, and effective system.

PMID- 16286404
TI  - Neuroform stent deployment for treatment of a basilar tip aneurysm via a
      posterior communicating artery route.
AB  - Coiling of a wide-necked basilar tip aneurysm can be accomplished in selected
      cases by placing a single Neuroform stent horizontally across the aneurysm neck
      via a posterior communicating artery approach rather than by placing 2 stents in
      a Y configuration via a basilar artery approach.

PMID- 16286405
TI  - Treatment of slow-flow (type I) perimedullary spinal arteriovenous fistulas with
      special reference to embolization.
AB  - Embolization of type I perimedullary spinal arteriovenous fistulas (AVFs) can be
      difficult, because of tortuosity and the small diameter of the feeder and distal
      location of the fistula site. The 1.5F flow-directed catheter in conjunction with
      a hydrophilic guidewire has been used in fistula embolization with cyanoacrylate
      glue for spinal vascular malformations at our institution. This combination has
      improved our success rate in achieving superselective catheterization of the
      fistula. Thus, 4 of 5 patients with type I perimedullary AVFs could be cured with
      this technique. Like type II and type III perimedullary AVFs, the endovascular
      approach may also be the first line of treatment in type I perimedullary spinal
      AVF.

PMID- 16286406
TI  - De novo development of a remote arteriovenous fistula following transarterial
      embolization of a carotid cavernous fistula: case report and review of the
      literature.
AB  - We report a case of a patient who developed a remote dural arteriovenous fistula
      involving the left sigmoid sinus 4 months after successful transarterial
      embolization of a carotid cavernous fistula. This rare occurrence has been
      reported after transvenous embolization, but this represents the first case, to
      our knowledge, after transarterial coil embolization. We present our findings
      along with a brief review of the literature.

PMID- 16286407
TI  - Endovascular recanalization of internal carotid artery occlusion in acute
      ischemic stroke.
AB  - BACKGROUND: Endovascular therapy (ET) of internal carotid artery (ICA) stenosis
      is equivalent to carotid endarterectomy for stroke prevention; however, patients
      with ICA occlusion and acute symptoms are traditionally not candidates for ET. We
      report our experience in endovascular recanalization of acute stroke patients
      with ICA occlusion. PATIENTS AND TECHNIQUES: We reviewed our registry for acute
      stroke patients treated with ET who had (1) ICA occlusion by digital subtraction
      angiography (thrombolysis in myocardial ischemia=0) with location of type II
      (above ophthalmic artery involving M1 or A1 but not both) or type III (proximal
      to the ophthalmic artery but distal to the bifurcation); (2) acute stroke
      symptoms from the index lesion presenting 3 hours after onset of symptoms; (3)
      minimal ischemic changes on brain CT scan (less than one third of the MCA
      territory); (4) attempted ET. Neuroradiologists reviewed angiograms for
      thrombolysis in cerebral infarction. A blinded vascular neurologist reviewed post
      procedural brain imaging for Alberta Stroke Program Early CT (ASPECT) scoring.
      Outcome scales were assessed. RESULTS: We identified 14 patients, 10 of whom were
      men (mean age, 58 +/- 14 years; median age, 54 years; age range, 40-74 years).
      There were 8 left ICA occlusions, 3 type II; and 6 right ICA occlusions, one type
      II. Median baseline National Institutes of Health Stroke Scale score was 17
      (range, 11-25; mean, 18 +/- 4.9). Mean time to ET was 389 +/- 103 minutes
      (median, 306 minutes; range, 197-1290 minutes). Immediate recanalization occurred
      in 64%. Decrease in expected stroke volume by brain imaging occurred in 50% with
      mean ASPECT score of 4 +/- 2.9 (median, 3; range, 0-8; 21% > or = 8). Two
      hemorrhages occurred, one symptomatic; 3 patients died. Good outcome was achieved
      in 64% of cases. CONCLUSION: Endovascular therapy of carotid occlusion in
      hyperacute stroke patients is feasible and may help to reduce stroke volume and
      increase good outcome in some patients.

PMID- 16286408
TI  - Intravenous glycoprotein IIb/IIIa inhibitor (tirofiban) followed by intra
      arterial urokinase and mechanical thrombolysis in stroke.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to evaluate preliminarily
      the efficacy and safety of intravenous tirofiban combined with intra-arterial
      pharmacologic and mechanical thrombolysis in patients with stroke. METHODS:
      Twenty-one consecutive patients with an acute ischemic stroke due to major
      cerebral arteries occlusion and a National Institutes of Health Stroke Scale
      [NIHSS] score > or = 18 were treated with an intravenous bolus of tirofiban and
      heparin followed by intra-arterial administration of urokinase coupled with
      mechanical thrombolysis. RESULTS: Thirteen patients had an anterior circulation
      stroke (T-siphon internal carotid artery [ICA] = 7; middle cerebral artery [MCA]
      = 6), 6 patients a posterior circulation stroke, and 2 patients an anterior plus
      posterior circulation stroke (left ICA or M1 tract of MCA plus basilar artery
      occlusions). Mean NIHSS score on admission was 21 (range, 18-27). Immediate
      recanalization was successful (thrombolysis in myocardial infarction [TIMI] 2-3)
      in 17 of 21 patients. The following day, 14 of 19 patients improved substantially
      and complete vessel patency (TIMI 3-4) was confirmed by digital subtraction
      angiography. Intracranial bleeding occurred in 5 of 21 patients (3 symptomatic
      cerebral hemorrhages and 2 subarachnoid hemorrhages) and was fatal in the case of
      3 patients. At discharge, the mean NIHSS was 5.4 (range, 0-25). Overall, at 3
      month follow-up the functional outcome was favorable (modified Rankin Scale score
      = 0-2) in 13 of 21 (62%) patients. Death (including all causes) at 90 days
      occurred in 6 of 21 (28%) cases. CONCLUSIONS: The combination of intravenous
      tirofiban with intra-arterial urokinase and mechanical thrombolysis may be
      successful in reestablishing vessel patency and result in a good functional
      outcome in patients with major cerebral arteries occlusions.

PMID- 16286409
TI  - Venous phase timing during balloon test occlusion as a criterion for permanent
      internal carotid artery sacrifice.
AB  - PURPOSE: The purpose of this study was to evaluate the reliability of angiography
      based balloon test occlusion (BTO) criteria to decide whether to perform internal
      carotid artery (ICA) permanent occlusion. METHODS: From March 1999 to August
      2004, 60 patients underwent therapeutic ICA occlusion. Angiographic BTO was
      performed systematically in all patients under general anesthesia (GA). No
      clinical examination test was performed. After balloon inflation, contralateral
      carotid and vertebral arteries angiograms were obtained. The symmetry of the
      venous phases of each hemisphere was assessed. Occlusion was considered to be
      feasible when the delay between the venous drainage of the injected and the
      occluded hemisphere was not >2 seconds. Venous drainage delay >4 seconds was
      considered as contraindication to ICA permanent occlusion. In patients with
      venous drainage delay of 2-4 seconds, the occlusion was performed only in
      selected cases. RESULTS: From a total of 60 patients, 44 had exact symmetry of
      the venous phase, 10 had delay of 1 second, and 3 other patients had 2-second
      delays. Clinical outcome for these 57 patients was uneventful. Three patients had
      venous drainage delay of 3 seconds. One of them had delayed watershed area
      infarction without clinical consequences at the time of hospital discharge. No
      periprocedural complications were observed. CONCLUSION: Venous opacification
      symmetry in the tested and control vascular territories was a reliable predictor
      of a subject's ability to tolerate carotid occlusion without developing
      neurologic deficit. Carotid sacrifice was found to be possible when the delay was
      <3 seconds.

PMID- 16286410
TI  - Shapability, memory, and luminal changes in microcatheters after steam shaping: a
      comparison of 11 different microcatheters.
AB  - PURPOSE: The purpose of this study was to compare the characteristics of shaped
      microcatheters, including shapability, durability, and luminal changes. MATERIALS
      AND METHODS: Eleven brands of steam-shaped microcatheters and one brand of
      preshaped microcatheter were evaluated. There were 2 nonreinforced and 10
      reinforced devices supported by coils. For evaluation of shapability, the tip
      angle of 6 samples of each brand were measured after steam-shaping for 20 seconds
      with a shaping mandrel bent at a 90 degrees or 150 degrees angle. The ability to
      maintain the shaped angle after guidewire insertion stress (durability) was
      compared by calculation of the change in the tip angle by using 3 samples of each
      brand. Luminal change after steam shaping was evaluated by calculation of
      narrowing rate of the smallest diameter and observation of the surface morphology
      of the mold of each catheter lumen by using a silicone polymer by means of a
      fluorescent projection method. RESULTS: The nonreinforced microcatheters and the
      fiber-braided microcatheter showed higher shapability than the others. The degree
      of distal microcatheter straightening with the microguidewire insertion was less
      pronounced in the preshaped microcatheter and the fiber-braided microcatheter.
      Spontaneous recovery to the initial tip angle 5 minutes after the guidewire
      procedure was observed in 10 brands to various degrees (87%-98%). Irregular
      luminal surface morphology at the angled portion was found in 6 reinforced
      brands. One nonreinforced catheter and the fiber-braided catheter showed high
      narrowing rates >6%. CONCLUSION: There are differences in shapabilty, durability,
      and luminal changes of steam shaping in 12 brands of microcatheters. These
      characteristics could be important factors in catheter choice for endovascular
      procedures.

PMID- 16286411
TI  - Nodular fasciitis in the head and neck: CT and MR imaging findings.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to describe the CT and MR
      imaging findings of nodular fasciitis occurring in the head and neck region.
      METHODS: CT (n = 6) and MR (n = 4) images obtained from 7 patients (3 men and 4
      women; mean age, 19.4 years; age range, 1-48 years) with surgically confirmed
      nodular fasciitis in the head and neck were retrospectively reviewed. All
      patients presented with a palpable mass in the head and neck that was noticed 1-3
      months earlier: 5 in the face, one in the occipital scalp, and the remaining one
      in the supraclavicular fossa. We investigated the CT and MR imaging
      characteristics with emphasis on the location, size, internal content, margin,
      enhancement pattern, and signal intensity of the lesion. RESULTS: All lesions
      appeared as a discrete mass on imaging, ranging from 1.0 cm to 4.6 cm in diameter
      (mean, 2.2 cm). Six lesions, all of which appeared benign, were located in the
      subcutaneous tissue superficial to the deep cervical fascia. The remaining lesion
      was located deep to the temporalis muscle and showed an aggressive imaging
      appearance, markedly eroding the bony orbit and skull. Five lesions were solid,
      and 2 lesions were partly or completely cystic in appearance. Five lesions were
      well defined, whereas 2 lesions were ill defined. Four of 5 solid lesions showed
      moderate to marked diffuse enhancement, whereas the remaining lesion demonstrated
      mild enhancement. Two cystic lesions showed peripheral, nodular, or rim-like
      enhancement. Compared with muscle, both solid lesions had isointense signal
      intensity on T1-weighted images and hyperintense signal intensity on T2-weighted
      images, whereas the signal intensity of the solid portions of the deep-seated,
      partly cystic lesion was isointense on both T1-weighted and T2-weighted images.
      CONCLUSION: Although rare, nodular fasciitis occurs as a discrete solid or cystic
      mass in the head and neck, depending on the predominant stromal components. When
      one sees a head and neck mass with a superficial location and moderate to marked
      enhancement on CT and MR imaging, nodular fasciitis should be included in the
      differential diagnosis, especially in patients with a recently developed, rapidly
      growing mass and a history of recent trauma.

PMID- 16286413
TI  - Resection of an orbital lymphangioma with the aid of an intralesional liquid
      polymer.
AB  - A 28-year-old man with long-standing right proptosis presented with an extensive
      multilobulated partially cystic orbital mass thought to be a lymphangioma.
      Because of concern that excision or debulking of the lesion was likely to be
      complicated by excessive bleeding, the lesion was injected with a mixture of
      ethiodized oil (Ethiodol) and cyanoacrylate glue under direct observation. The
      mixture caused the injected lobules to assume a firm, rubbery texture, allowing
      them to be excised without bleeding.

PMID- 16286412
TI  - Evaluation of the upper airway cross-sectional area changes in different degrees
      of severity of obstructive sleep apnea syndrome: cephalometric and dynamic CT
      study.
AB  - BACKGROUND AND PURPOSE: The upper airway lumen is narrower in patients with
      obstructive sleep apnea syndrome (OSAS) than normal subjects. In this study, we
      examined changes of the upper airway cross-sectional area in each phase of
      respiration in different degrees of severity of OSAS with dynamic CT and
      investigated whether these changes have any correlation with sleep apnea severity
      parameters, including polysomnography (PSG) and cephalometry. MATERIALS AND
      METHODS: Between May and November 2004, 47 patients who had at least 2 of 3 major
      symptoms of snoring, daytime somnolence, and apnea with witness were included in
      this prospective study. As control group, 24 habitual snorers were studied. All
      patients underwent PSG and upper airway CT. The average number of episodes of
      apnea and hypopnea per hour of sleep (the apnea-hypopnea index, AHI) was
      calculated. An AHI of 5 -29 represented mild/moderate OSAS and an AHI > or = 30
      represented severe OSAS. Cross-sectional area of the airway at the level of
      oropharynx and hypopharynx were obtained in each phase of quiet tidal breathing
      and at the end of both the forced inspiration and expiration. Six standard
      cephalometric measurements were made on the lateral scout view. All parameters
      were compared between controls and mild/moderate and severe OSAS groups. RESULTS:
      Twenty-seven patients had mild/moderate OSAS, and 20 patients had severe OSAS.
      Patients with severe OSAS had significantly narrower cross-sectional area at the
      level of uvula in expiration, more inferiorly positioned hyoid bone, and thicker
      soft palate compared with patients with mild/moderate OSAS (P < .05) and the
      control group (P < .05). In addition, severe OSAS patients had bigger neck
      circumference than those in the control group (P < .05). CONCLUSION: Patients
      with severe OSAS had significant differences in the parameters. Measurement of
      the cross-sectional area of oropharynx in expiration can especially be useful for
      diagnosis of severe OSAS as a new key point.

PMID- 16286414
TI  - Agenesis of bilateral internal carotid arteries and posterior fossa abnormality
      in a patient with facial capillary hemangioma: presumed incomplete phenotypic
      expression of PHACE syndrome.
AB  - PHACE syndrome is a neurocutaneous syndrome with the following features:
      posterior fossa malformations of the brain, large facial hemangiomas, arterial
      anomalies, cardiac anomalies and aortic coarctation, and eye abnormalities. We
      report a rare case of bilateral internal carotid artery agenesis with
      transcranial collaterals from the external carotid arteries and agenesis of the
      vertebrobasilar system in a possible PHACE syndrome. We suggest that the patient
      had an incomplete phenotypic expression of the PHACE syndrome. Although the
      phenotypic spectrum is broad and is still largely unexplored, the extent of the
      cephalic neural crest cells insulted genetically or by other causes at a certain
      time during the development of the embryo might explain the variable phenotypic
      expression of PHACE syndrome.

PMID- 16286415
TI  - CT demonstration of dacryolithiasis complicated by dacryocystitis.
AB  - Cross-sectional imaging has demonstrated an increasing role in the evaluation of
      the orbits and the periorbital structures. The case presented in this article
      demonstrates the rare finding of a dacryolith by CT. To our knowledge, little has
      been reported on cross-sectional imaging characteristics of this entity in the
      recent radiologic literature. We demonstrated that CT can be a useful tool in
      diagnosing both dacryolithiasis and dacryocystitis. Obtaining an early diagnosis
      of dacryolithiasis is optimal to avoid potential complications, particularly
      because treatment is often curative.

PMID- 16286416
TI  - CT and MRI appearances of primary sphenoid melanoma: a rare case.
AB  - Primary sphenoid melanoma is a rare tumor. A 75-year-old man presented with
      complaints of headache and visual complaints for a few days. CT and MRI of the
      brain demonstrated a sphenoid sinus mass with appearances suggesting a diagnosis
      of melanoma. Fine-needle aspiration biopsy confirmed the diagnosis. Other
      differential diagnostic considerations on CT and MRI are discussed. We also
      discuss the further role of contrast MRI in determining the actual extent of the
      tumor in the critical skull base area.

PMID- 16286417
TI  - Incidence of vertebral artery thrombosis in cervical spine trauma: correlation
      with severity of spinal cord injury.
AB  - BACKGROUND AND PURPOSE: The incidence of blunt traumatic vertebral artery
      dissection/thrombosis varies widely in published trauma series and is associated
      with spinal trauma. The purpose of this study was to determine the frequency of
      traumatic vertebral artery thrombosis (VAT) in cervically injured patients by
      using routine MR angiography (MRA) and MR imaging and identify associations with
      the severity of neurologic injury. METHODS: A retrospective review of 1283
      patients with nonpenetrating cervical spine fractures with or without an
      associated spinal cord injury (SCI) was performed. Imaging consisted of routine
      cervical MR imaging and 2D time-of-flight MRA of the neck. The cervical injury
      level, neurologic level of injury, and American Spinal Injury Association (ASIA)
      grade were recorded. RESULTS: In this study, 632 patients met the inclusion
      criteria, 83 (13%) of whom had VAT on the admission MR imaging/MRA. Fifty-nine
      percent (49/83) of VAT patients had an associated SCI. VAT was significantly more
      common in motor-complete patients (ASIA A and B, 20%) than in neurologically
      intact (ASIA E, 11%) cervical spine-injured patients (P = .019). VAT incidence
      was not significantly different between motor-incomplete (ASIA C and D, 10%) and
      neurologically intact (ASIA E, 11%) cervical spine-injured patients (P = .840).
      CONCLUSION: The absence of neurologic symptoms in a patient with cervical spine
      fracture does not preclude VAT. VAT associated with cervical spinal injury occurs
      with similar frequency in both neurologically intact (ASIA E) and motor
      incomplete patients (ASIA C and D) but is significantly more common in motor
      complete SCI (ASIA A and B).

PMID- 16286419
TI  - MR imaging of a posterior mediastinal ganglioneuroma: fat as a useful diagnostic
      sign.
AB  - We report a case of a ganglioneuroma that was found incidentally on a CT of the
      abdomen in a 27-year-old woman with gastrointestinal symptoms. The tumor, though
      located in the posterior mediastinum, demonstrated an unusual feature of abundant
      adipose tissue on MR imaging. The mass was later resected, and adipose tissue
      intermixed within a ganglioneuroma was identified microscopically. Adipose tissue
      is a rare finding in a ganglioneuroma, but this radiographic feature may be
      useful in the evaluation of posterior mediastinal masses.

PMID- 16286418
TI  - Evaluation of vertebroplasty with a validated outcome measure: the Roland-Morris
      Disability Questionnaire.
AB  - BACKGROUND AND PURPOSE: Vertebroplasty is rapidly disseminating as a treatment
      for vertebral compression fractures, but its efficacy has not been assessed with
      a well-validated, back pain-specific instrument. We report the use of the Roland
      Morris Disability Questionnaire (RDQ) in patients undergoing vertebroplasty for
      painful osteoporotic compression fractures. METHODS: Retrospective review of
      patients treated with vertebroplasty who completed the RDQ and 2 verbal pain
      scales (0-10) for pain at rest and pain with activity at baseline, 1 week, 1
      month, 6 months, and 1 year post-vertebroplasty. Changes in outcome measures were
      analyzed by using a paired t test and correlations were assessed with Spearman
      rho. Multiple linear regression was used to analyze the relationship between
      baseline scores and independent variables. RESULTS: One hundred thirteen patients
      were treated at 164 vertebral levels. At baseline, RDQ scores were associated
      with rest and activity pain (P < .001 and P = .002, respectively) but were not
      associated with other independent variables. All 3 outcome scores decreased by 1
      week and remained improved through maximal follow-up (P < .001). RDQ scores
      improved by a mean of 7.0 points at 1 week and remained improved at 1 year (P =
      .02). RDQ scores correlated with both rest and activity pain, but the absolute
      correlation was slightly better (+0.15 on average) with activity pain.
      CONCLUSIONS: Patients who underwent vertebroplasty experienced relief of back
      pain and symptoms, as shown by improvement in verbal pain and RDQ scores. The RDQ
      correlates well with measures of pain, shows clinically significant improvement
      and is responsive to changes across time. More important, the RDQ provides an
      easily administered, well-validated, back pain-specific outcome measure that
      could be adopted to assess vertebroplasty outcomes.

PMID- 16286420
TI  - Epidural blood patch at C2: diagnosis and treatment of spontaneous intracranial
      hypotension.
AB  - Spontaneous intracranial hypotension in a 37-year-old man with intractable
      headaches was diagnosed on MR imaging. A generous CSF leak was identified at C2
      on CT myelography. Successful treatment was performed with CT-guided blood patch
      at the leakage site after the patient had failed 2 lumbar blood patches. Imaging
      guided precise placement of the blood patch is safe and recommended when a lumbar
      blood patch away from the leakage site could be ineffective.

PMID- 16286421
TI  - Inflammatory pseudotumor in the epidural space of the thoracic spine: a case
      report and literature review of MR imaging findings.
AB  - We present a rare case of pathologically proven inflammatory pseudotumor in the
      thoracic spine. The lesion showed an isointense signal on T1-weighted images, a
      heterogeneous iso- and hyperintense signal on T2-weighted images, and strong
      homogeneous enhancement. There was no evidence of abnormalities in the adjacent
      bone. Whereas the exact pathogenesis of this lesion is unknown, it has been
      regarded as an unusual response to insults such as trauma or acute infection, a
      post-inflammatory reparative process, or low-grade malignancy.

PMID- 16286422
TI  - Structural, immunocytochemical, and mr imaging properties of periventricular
      crossroads of growing cortical pathways in preterm infants.
AB  - BACKGROUND AND PURPOSE: Periventricular white matter (WM) areas are widely
      recognized as predilection sites for complex cellular damage after
      ischemia/reperfusion or inflammatory injury of the perinatal cerebrum. We
      analyzed histochemical and MR imaging properties of fiber architectonics and
      extracellular matrix (ECM) of periventricular areas to disclose the potential
      significance of topographically specific WM lesions for the neurodevelopmental
      outcome. METHODS: We combined histochemical methods for demonstration of fibers,
      axonal guidance molecules, and ECM with T1-weighted MR images on postmortem
      specimens aged 15 to 36 postovulatory weeks (POW) and T2-weighted MR images on in
      vivo fetuses aged 14 to 26 POW. RESULTS: The fiber architectonics of the fetal
      cerebrum display tangential axon strata in frontopolar and occipitopolar regions,
      whereas the central periventricular region contains crossroads of intersecting
      callosal (transverse), associative (sagittal), and thalamocortical/corticofugal
      (radial) fiber bundles. In early preterms, crossroads contain hydrophylic ECM
      with axonal guidance molecules, and they are easily recognized as hypointensities
      on T1-weighted MR images or hyperintensities on T2-weighted MR images. After the
      28 POW, tangential fetal fiber-architectonic stratification transforms into the
      corona radiata system; however, the growth of cortical pathways continues in
      crossroad areas, as indicated by the presence of ECM and their distinct MR
      imaging signal intensities. CONCLUSIONS: The correlation of MR imaging with
      histochemical findings demonstrated the presence of periventricular fiber
      crossroads rich in ECM and axonal guidance molecules. We propose that, in
      perinatal WM lesions, periventricular WM crossroads represent a hitherto
      unrecognized and vulnerable cellular and topographic target in which combined
      damage of association-commissural and projection fibers may explain the
      complexity of cognitive, sensory, and motor deficit in survivors of
      periventricular WM lesions.

PMID- 16286423
TI  - Growth rate of corpus callosum in very premature infants.
AB  - BACKGROUND AND PURPOSE: It is desirable to develop a bedside method for assessing
      cerebral development in the very premature infant to monitor the effectiveness of
      interventions aimed at improving cerebral development. Our aim was to describe
      the growth trajectory of the corpus callosum (CC) on cranial sonography in very
      premature infants. METHODS: We recruited 100 very-low-birth-weight infants
      admitted to a single regional level III neonatal intensive care unit from
      November 1998 to November 2000. Cranial sonography images of the CC were obtained
      for 64 (32 boys) infants (mean gestational age, 28 weeks; range, 23-33 weeks) in
      the first week of life and at term equivalency. The growth rate of the CC was
      compared in the 64 study infants to the expected growth rate of 0.20-0.27 mm/day
      from antenatal data and correlated with clinical outcome at 2 years of age by
      using Mental Development Index (MDI) and Psychomotor Development Index (PDI).
      RESULTS: The average growth rate of the CC was half of that expected from
      antenatal data. Mean growth rates were similar for all gestational ages (mean,
      0.11 mm/day; range, 0.05-0.29; P = .4). The CC at term equivalency was longer for
      those in MDI class 2 (mean, 44.3 mm) compared with MDI class 3 (mean 40.2 mm; P =
      .003) as well as for PDI class 2 versus 3 (P = .017). CONCLUSION: Measurement of
      the length of the CC at cranial sonography is reproducible. Those with poorer
      neurodevelopmental outcomes have a shorter CC at term equivalency. The CC grows
      at a much lower rate postnatally than in utero among very premature infants.

PMID- 16286424
TI  - Qualitative assessment of brain anomalies in adolescents with mental retardation.
AB  - BACKGROUND AND PURPOSE: The neural basis of mental retardation is poorly
      understood. This study aimed to characterize structural anomalies of the brain in
      mental retardation and the relationship between them and the degree of mental
      retardation. METHODS: Eighty adolescents receiving educational support and 40
      controls underwent MR brain imaging and intelligence quotient (IQ) assessment. MR
      images were evaluated according to a checklist of qualitative brain anomalies by
      a neuroradiologist blind to group membership. All scans were assessed by a second
      neuroradiologist to measure interobserver agreement. Ten percent of the studies
      were randomly selected for assessment of intraobserver agreement. RESULTS:
      Evaluation of MR images by using the checklist generated results with a high
      degree of interobserver and intraobserver agreement. Intraclass correlations were
      0.93 and 0.75 for interobserver agreement on the total abnormality score and the
      entire checklist, respectively, and 0.97 and 0.85 for intraobserver agreement on
      the total abnormality score and the entire checklist, respectively. IQ is
      negatively correlated with the total abnormality score (P < .001). Subjects with
      an IQ <70 have a significantly greater total score (P = .003) and a significantly
      greater score for 12 specific anomalies, including thinning of the corpus
      callosum (P = .001) and abnormalities of the lateral ventricles. CONCLUSION:
      Mental retardation is associated with demonstrable brain anomalies, particularly
      thinning of the corpus callosum and ventricular abnormalities, and with a high
      total abnormality score. Greater levels of brain anomalies are associated with
      greater levels of mental retardation as evidenced by IQ.

PMID- 16286426
TI  - Characteristic MR imaging changes in severe hypermethioninemic states.

PMID- 16286428
TI  - Effect of L-carnitine on the kinetics of carnitine, acylcarnitines and
      butyrobetaine in long-term haemodialysis.
AB  - BACKGROUND: The current study was performed to investigate the kinetics of
      carnitine, individual acylcarnitines and butyrobetaine in patients on
      haemodialysis. METHODS: Eight stable long-term haemodialysis patients were
      studied under basal conditions (no carnitine supplementation) and 3 weeks after
      intravenous supplementation with l-carnitine (10 or 20 mg/kg body weight) after
      each haemodialysis session. The kinetic studies included serial determinations of
      carnitine and metabolites just before, during or between haemodialysis sessions.
      Analysis was performed by liquid chromatography-tandem mass spectrometry.
      RESULTS: Before haemodialysis, the plasma concentrations were (micromol/l) 15.1+/
      0.6 (mean+/-SEM) for carnitine, 5.9+/-0.7 for acetylcarnitine, 0.66+/-0.04 for
      propionylcarnitine and 0.98+/-0.08 for butyrobetaine (basal conditions) or 142+/
      23 for carnitine, 69+/-12 for acetylcarnitine, 6.0+/-1.1 for propionylcarnitine
      and 2.6+/-0.3 for butyrobetaine (carnitine 20 mg/kg). During haemodialysis, the
      plasma concentrations dropped by approximately 80% for all compounds determined,
      with extraction coefficients ranging from 0.65 to 0.86. In patients supplemented
      with 20 mg/kg carnitine, the amount of carnitine removed by haemodialysis
      equalled 42% of the dose administered, consisting of 2.08 mmol carnitine, 1.03
      mmol acetylcarnitine and 0.051 mmol propionylcarnitine. Between the haemodialysis
      sessions, carnitine, acylcarnitines and butyrobetaine reached apparent steady
      state concentrations within 1 day both under basal conditions and after
      supplementation. CONCLUSIONS: Patients on haemodialysis have reduced carnitine,
      acylcarnitine and butyrobetaine plasma levels, which can be increased by
      supplementing carnitine. Propionylcarnitine, an important constituent of the
      acylcarnitine pool, can be removed by haemodialysis. Removal of potentially toxic
      acyl-groups may represent a mechanism for a beneficial effect of carnitine in
      these patients.

PMID- 16286430
TI  - Bladder vs enteric drainage in simultaneous pancreas-kidney transplantation.
AB  - BACKGROUND: As a valid therapeutic option for patients with type 1 diabetes
      mellitus (IDDM) and secondary diabetic nephropathy, simultaneous pancreas-kidney
      (SPK) transplantation remains more undeveloped than other solid organ
      transplantations due to restrictions of surgical techniques, especially modes of
      exocrine pancreatic secretion. Enteric drainage (ED) has recently been
      increasingly popular due to the long-term complications with bladder drainage
      (BD). Objectives. Compare results of SPK transplants with enteric vs bladder
      exocrine drainage since the beginning of our experience with this type of
      transplantation. METHODS: From March 1998 to October 2004, 53 SPK transplants
      were performed, consisting of 30 with bladder drainage (BD) and 23 with enteric
      drainage (ED). Induction therapy included antilymphocyte globulin (ALG) or anti
      CD25 monoclonal antibody. Maintenance regimen consisted of tacrolimus
      (TAC)/cyclosporine (CsA), mycophenolate mofetil (MMF) and steroids. RESULTS: Mean
      age of recipients was 39+/-7 in both groups. No anastomosis leakage occurred in
      either group. Surgical complications were not significantly different between the
      two groups. Incidence of acute rejection, major infections and cytomegalovirus
      disease were also similar. However, the BD group was characterized by a slight
      increase in number of urologic complications, metabolic acidosis and dehydration.
      The length of initial hospital stay was likewise comparable. All patients with a
      functional graft no longer required exogenous insulin. BD actuarial patient
      survival and graft three-year survival were 96 and 86%, respectively. For ED, the
      respective results were 97 and 91%, respectively. CONCLUSION: Compared with BD,
      perioperative morbidity is not increased by ED, and ED is not associated with
      increased long-term pancreas graft failure. These data suggest that ED is
      superior to BD and should be considered as the preferred technique for
      simultaneous pancreas-kidney transplants.

PMID- 16286429
TI  - Update on adverse drug events associated with parenteral iron.
AB  - BACKGROUND: We previously compared the safety profile of three formulations of
      intravenous iron used during 1998-2000 and found higher rates of adverse drug
      events (ADEs) associated with the use of higher molecular weight iron dextran and
      sodium ferric gluconate complex compared with lower molecular weight iron
      dextran. Since that time, iron sucrose has become widely available and clinicians
      have gained additional experience with sodium ferric gluconate complex. METHODS:
      We obtained data from the United States Food and Drug Administration (FDA) on
      ADEs attributed to the provision of four formulations of intravenous iron during
      2001-2003, including higher and lower molecular weight iron dextran, sodium
      ferric gluconate complex and iron sucrose. We estimated the odds of intravenous
      iron-related ADEs using 2 x 2 tables and the chi(2) test. RESULTS: The total
      number of reported parenteral iron-related ADEs was 1141 among approximately
      30,063,800 doses administered, yielding a rate of 3.8 x 10(-5), or roughly 38 per
      million. Eleven individuals died in association with the ADE. Relative to lower
      molecular weight iron dextran, total and life-threatening ADEs were significantly
      more frequent among recipients of higher molecular weight iron dextran and
      significantly less frequent among recipients of sodium ferric gluconate complex
      and iron sucrose. The absolute rates of life-threatening ADEs were 0.6, 0.9, 3.3
      and 11.3 per million for iron sucrose, sodium ferric gluconate complex, lower
      molecular weight iron dextran and higher molecular weight iron dextran,
      respectively. Based on differences in the average wholesale price of iron sucrose
      and lower molecular weight iron dextran in the US, the cost to prevent one life
      threatening ADE related to the use of lower molecular weight iron dextran was
      estimated to be 5.0-7.8 million dollars. The cost to prevent one lower molecular
      weight iron dextran-related death was estimated to be 33 million dollars.
      CONCLUSIONS: The frequency of intravenous iron-related ADEs reported to the FDA
      has decreased, and overall, the rates are extremely low. This is the fourth
      report suggesting increased risks associated with the provision of higher
      molecular weight iron dextran. Life-threatening and other ADEs appear to be lower
      with the use of non-dextran iron formulations, although the cost per ADE
      prevented is extremely high.

PMID- 16286431
TI  - Time to return to work and surgeons' recommendations after carpal tunnel release.
AB  - BACKGROUND: Time to return to work after carpal tunnel release is extremely
      variable suggesting that only a small proportion of total sick-leave is for
      medical reasons. AIMS: To determine factors predicting a delayed return to work.
      METHODS: Fifty consecutive employed patients undergoing carpal tunnel surgery
      were tested pre-operatively, and then at 1 month post-operatively using both
      questionnaires and objective testing. Further follow-up by telephone was carried
      out every 2 weeks up until 90 days. RESULTS: Forty-nine of the 50 workers had
      returned to work by 3 months. Time to return to work was extremely variable
      ranging from 1 to 88 days in those who returned to work. Post-operative
      recommendations by the surgeon also varied widely from 1 to 36 days. The
      surgeons' recommendations were the strongest predictors of delayed return to work
      [odds ratio 30.5; 95% confidence interval (CI), 3.2-288], with physical work
      (odds ratio 27.7; 95% CI, 1.5-507) and lack of self-rated health (odds ratio 5.0;
      95% CI, 1.11-100) adding significantly to the logistic regression model, which
      was highly predictive (area under the receiver-operator curve of 88%). Patient
      symptoms and objective findings of disability did not add significantly to a
      logistic regression model either predicting return to work or the surgeon's
      recommendations. CONCLUSIONS: Our study suggests that workers will return to work
      in less than 3 weeks if recommended by the surgeon. A randomized controlled trial
      is warranted to determine if a higher proportion of workers returning in less
      than 3 weeks can be obtained by standardizing surgeons' recommendations.

PMID- 16286433
TI  - Searching bibliographic databases for literature on chronic disease and work
      participation.
AB  - BACKGROUND: The work participation of people with chronic diseases is a growing
      concern within the field of occupational medicine. Information on this topic is
      dispersed across a variety of data sources, making it difficult for health
      professionals to find relevant studies for literature reviews and guidelines.
      AIM: The goal of this project was to identify bibliographic databases and search
      terms that could be most useful for retrieving relevant studies on this topic.
      METHODS: Five broad questions regarding work participation and chronic disease
      were formulated, focusing on angina pectoris, depression, diabetes mellitus,
      hearing impairment and rheumatoid arthritis. A search strategy for retrieving
      information on these questions was developed and run in five bibliographic
      databases: Medline, EMBASE, PsycINFO, Cinahl and OSHROM. Relevant publications
      were selected from the search results. The utility of the selected databases and
      search terms was evaluated by analysing the number of relevant publications that
      were retrieved. RESULTS: The number of relevant publications retrieved from each
      database varied. Most (84%) of the relevant publications that were retrieved from
      each database were unique to that source. For each database, specific search
      terms for the concept of 'work' were useful for retrieving relevant publications.
      CONCLUSION: Medline, EMBASE and PsycINFO are useful databases for quick searches.
      Useful search terms for the concept of 'work' are work capacity, work disability,
      vocational rehabilitation, occupational health, sick leave, absenteeism, return
      to work, retirement, employment status and work status. For comprehensive
      searches, we recommend additional searches in Cinahl and OSHROM, adapting the
      search terms to specific databases.

PMID- 16286432
TI  - Systematic review of studies of productivity loss due to rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic, debilitating disease with a
      significant impact on workplace productivity. AIM: To perform a systematic review
      of studies of the relationship between RA and reduced workplace productivity.
      METHODS: Screening of 307 titles identified in bibliographic database searches
      resulted in 38 articles subject to systematic review. Productivity loss was
      expressed by three different measures: work disability, work loss (synonymous
      with absenteeism or short-term sick leave) and work limitation (reduction in
      productivity while present at work). RESULTS: A median of 66% (range 36-84%) of
      employed RA subjects experienced work loss due to RA in the previous 12 months,
      for a median duration of 39 days (range 7-84 days). The times from RA diagnosis
      until a 50% probability of being work disabled varied from 4.5 to 22 years. In
      inception cohort studies, the baseline variables consistently predictive of
      subsequent work disability were a physically demanding work type, more severe RA
      and older age. CONCLUSIONS: RA-related work-disability rates were similar in the
      USA and European countries. An apparent decrease in the prevalence of RA-related
      work disability since the 1970s may be related to a decrease in physically
      demanding work rather than to epidemiologic changes in RA. The majority of the
      literature addresses permanent disability and temporary work loss; none of the
      studies reviewed reported the effect of RA on presenteeism, i.e. work limitation
      from the employer perspective, and there are few published studies of the
      effectiveness of disease-modifying anti-rheumatic drugs in reducing work-related
      productivity loss.

PMID- 16286434
TI  - Research and care of patients with dementia: moving beyond memory loss.

PMID- 16286435
TI  - Emotion-discrimination deficits in mild Alzheimer disease.
AB  - OBJECTIVE: Mild Alzheimer disease (AD) preferentially affects temporal lobe
      regions, which represent important structures in memory and emotional processes.
      This study investigated emotion discrimination in people with mild AD, versus
      Caretakers. METHODS: Twenty AD subjects and 22 caretakers underwent computerized
      testing of emotion recognition and differentiation. Performances between groups
      were compared, controlling for possible effects of age and cognitive abilities.
      RESULTS: AD subjects showed diminished recognition of happy, sad, fearful, and
      neutral expressions. They also exhibited decreased differentiation between happy
      and sad expressions. Controlling for effects of cognitive dysfunction, AD
      subjects differed on recognition of happy and sad, and differentiation of sad
      facial expressions, and in error patterns for fearful and neutral faces.
      CONCLUSIONS: Diminished abilities for emotion discrimination are present in
      persons with mild AD. In persons with mild AD, who frequently reside in their own
      home or with close family, this diminished ability may adversely affect social
      functioning and quality of life.

PMID- 16286436
TI  - Frontal lobe hypometabolism and impaired insight in Alzheimer disease.
AB  - OBJECTIVE: The authors examined the relationship between impaired insight
      regarding cognitive and functional deficits and frontal cortex hypometabolism in
      41 patients with Alzheimer disease (AD). METHODS: Regional cerebral glucose
      metabolism was determined with (18F)fluorodeoxyglucose and positron emission
      tomography. Level of insight was measured with the clinician-rated
      Neurobehavioral Rating Scale, and severity of global cognitive impairment was
      determined with the Mini-Mental State Exam. RESULTS: Inaccurate insight was
      correlated with glucose metabolic rate in the right lateral frontal cortex
      (Brodmann areas 6 and 45, and the lateral aspect of Brodmann areas 8 and 9) after
      controlling for global cognitive dysfunction. CONCLUSIONS: The findings from this
      study help to further elucidate the neurobiological mechanisms underlying
      impaired insight in AD, indicating a link between this important clinical
      phenomenon and dysmetabolism in a focal region of the right prefrontal cortex.

PMID- 16286437
TI  - Divalproex sodium in nursing home residents with possible or probable Alzheimer
      Disease complicated by agitation: a randomized, controlled trial.
AB  - OBJECTIVE: Three placebo-controlled clinical trials have suggested the benefit of
      valproate for treatment of agitation associated with dementia; one was used as
      the basis for this multicenter trial, conducted by the Alzheimer's Disease (AD)
      Cooperative Study. It addresses the efficacy, safety, and tolerability of
      divalproex sodium for the treatment of agitation associated with dementia.
      METHODS: This was a randomized, double-blind, placebo-controlled clinical trial
      in 153 nursing home residents with probable or possible AD complicated by
      agitation; 110 (72%) completed the trial. Participants were randomized to
      treatment with divalproex sodium at a target dose of 750 mg/day (N = 75) or
      placebo (N = 78) for 6 weeks. The primary outcome measure was change from
      baseline on the Brief Psychiatric Rating Scale (BPRS) Agitation factor. Secondary
      outcomes included total BPRS, Clinical Global Impression of Change, Cohen
      Mansfield Agitation Inventory score, and measures of safety and tolerability.
      RESULTS: Compliance averaged 88%. Participants receiving divalproex achieved a
      mean dose of 800 mg/day. Change in mean BPRS Agitation factor scores did not
      differ between patients treated with divalproex and placebo, nor did secondary
      behavioral measures. Measures of safety and tolerability did not reveal
      clinically important drug/placebo differences. CONCLUSIONS: This multicenter
      trial showed no benefit of divalproex sodium for treatment for agitation in
      dementia at a mean dose of 800 mg/day over 6 weeks. The results do not support
      findings from previous trials indicating possible benefit.

PMID- 16286438
TI  - Preserved cognition in patients with early Alzheimer disease and amnestic mild
      cognitive impairment during treatment with rosiglitazone: a preliminary study.
AB  - OBJECTIVE: Insulin resistance (impaired insulin action) has been associated with
      Alzheimer disease (AD) and memory impairment, independent of AD. Peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma) agonists improve insulin
      sensitivity and regulate in-vitro processing of the amyloid precursor protein
      (APP). Authors evaluated the effects of the PPAR-gamma agonist rosiglitazone on
      cognition and plasma levels of the APP derivative beta-amyloid (Abeta) in humans.
      METHODS: In a placebo-controlled, double-blind, parallel-group pilot study, 30
      subjects with mild AD or amnestic mild cognitive impairment were randomized to a
      6-month course of rosiglitazone (4 mg daily; N = 20) or placebo (N = 10). Primary
      endpoints were cognitive performance and plasma Abeta levels. RESULTS: Relative
      to the placebo group, subjects receiving rosiglitazone exhibited better delayed
      recall (at Months 4 and 6) and selective attention (Month 6). At Month 6, plasma
      Abeta levels were unchanged from baseline for subjects receiving rosiglitazone
      but declined for subjects receiving placebo, consistent with recent reports that
      plasma Abeta42 decreases with progression of AD. CONCLUSIONS: Findings provide
      preliminary support that rosiglitazone may offer a novel strategy for the
      treatment of cognitive decline associated with AD. Future confirmation in a
      larger study is needed to fully demonstrate rosiglitazone's therapeutic
      potential.

PMID- 16286439
TI  - Racial differences in the progression of cognitive decline in Alzheimer disease.
AB  - OBJECTIVE: Alzheimer disease (AD) is the leading cause of dementia in older
      persons, but little is known about racial differences in its clinical
      manifestations. The purpose of the current study was to examine the association
      of race with rate of cognitive decline in AD. METHODS: Older persons with
      clinically diagnosed AD were recruited from healthcare settings. At 6-month
      intervals for up to 4 years, they completed a battery of nine cognitive tests
      from which a previously established measure of global cognition was derived.
      Follow-up data were available on 452 participants (27.6% African American, 68.8%
      women), 88.1% of those eligible. RESULTS: A growth curve approach was used to
      estimate individual paths of change in global cognition. In a model that
      controlled for age and education, African Americans had a lower level of global
      cognition at baseline than non-African Americans, but declined at a 25% slower
      rate on average. In additional models, there was no indication that the
      association of race with cognitive decline varied by age, gender, or education.
      CONCLUSION: The rate of cognitive decline in AD appears to be slower in African
      Americans than non-African Americans.

PMID- 16286440
TI  - Racial differences in cognitive decline in a sample of community-dwelling older
      adults: the mediating role of education and literacy.
AB  - OBJECTIVE: The authors examined racial differences in cognitive decline (CD) and
      the role of education and literacy in mediating this relationship. METHODS: The
      relationship between race and CD was examined over a 3-year period in a biracial
      community sample of older adults (N = 3,097) living in North Carolina. RESULTS:
      African Americans, as compared with White participants, had fewer years of
      education and were more likely to be assessed by the interviewer as not literate.
      Race predicted CD such that African Americans had higher rates than Whites. When
      education and literacy were entered into the analysis, the association between
      race and CD, although remaining statistically significant, was reduced and was of
      relatively weak magnitude. Also, physical functioning problems also predicted CD
      and were found to be greater in African Americans than in Whites. CONCLUSIONS:
      Education and literacy may be protective factors against CD. Socioeconomic
      disadvantages experienced by older African Americans in the South early in life,
      leading to poorer educational opportunities, may explain, in part, the increased
      rates of CD in older African Americans versus Whites.

PMID- 16286442
TI  - Hallucinations and mortality in Alzheimer disease.
AB  - OBJECTIVE: The authors tested the relationship of hallucinations and delusions to
      mortality in Alzheimer disease (AD). METHODS: A group of 407 persons with
      clinically diagnosed AD completed a uniform clinical evaluation, after which
      vital status was monitored for a mean of 3.7 years. At the initial evaluation, a
      previously established, structured, informant interview was used to ascertain the
      presence of hallucinations and delusional thinking. The evaluation also included
      a structured medical history, inspection of all medications, and detailed
      assessment of cognitive functioning and parkinsonian signs. RESULTS: At study
      onset, hallucinations were present in 41.0% of participants and delusions in
      54.4%. During follow-up, 146 deaths occurred. In a proportional-hazards model
      adjusted for age, sex, race, and education, hallucinations were associated with a
      78% increase in risk of death. The association was not substantially altered in
      subsequent analyses that controlled for level of cognitive impairment, severity
      of parkinsonism, use of antipsychotic medications, and the presence of chronic
      medical conditions. Risk of death was more than doubled in those with both
      auditory and visual hallucinations. By contrast, we did not find evidence of an
      association of delusions with mortality. CONCLUSION: Hallucinations are
      associated with an increased risk of death in AD.

PMID- 16286441
TI  - Persistence of and changes in neuropsychiatric symptoms in Alzheimer disease over
      6 months: the LASER-AD study.
AB  - OBJECTIVES: Neuropsychiatric symptoms (NPS) are common in Alzheimer disease (AD).
      It is important in terms of management to know their natural history and their
      effects on service use. The authors aimed to determine the persistence and change
      in severity of NPS over 6 months in participants with AD, and the relationship to
      initial severity, drug management, use of services, and cost of care. METHODS:
      NPS scores and data on cognition, psychotropic medication, service use, and costs
      of care were collected on 224 participants at baseline and on 198 at 6-month
      follow-up. RESULTS: Of 224 patients, 210 (93.8%) had NPS at baseline; 168 (75.0%)
      had at least one clinically significant symptom, 118 (80.4%) of whom had
      persistent significant symptoms at 6-month follow-up. There was no significant
      change in mean NPS score for any symptom over 6 months, but many individuals
      became better or worse; 61.2% of those with at least one significant baseline
      symptom in any domain improved. Those with persistent symptoms had more severe
      baseline symptoms. Deterioration in NPS was predicted by deterioration in MMSE.
      Those with at least one clinically significant symptom had higher care costs than
      those without. CONCLUSIONS: NPS were highly persistent overall, but many
      individuals became better or worse. Persistence was predicted by having more
      severe symptoms at baseline. Clinically significant levels of NPS were associated
      with greater costs of care. The relatively few associations found between
      specific psychiatric treatments and changes in NPS reflect both undertreatment
      and the complexity of symptoms.

PMID- 16286443
TI  - Factor analysis of the Cohen-Mansfield Agitation Inventory in three large samples
      of nursing home patients with dementia and behavioral disturbance.
AB  - OBJECTIVE: Limited work has addressed the construct validity of the Cohen
      Mansfield Agitation Inventory (CMAI) in nursing home patients. The authors tested
      the CMAI factor structure by use of data from three samples of nursing home
      patients categorized a priori as having at least mild behavioral and
      psychological symptoms of dementia. METHODS: CMAI data were from the baseline
      assessment of three randomized, placebo-controlled trials of risperidone for
      treating elderly nursing home patients. Exploratory factor analyses were
      conducted on two trials (N = 304; N = 344), and the results of these exploratory
      factor analyses were then tested with confirmatory factor analysis by use of data
      from a third trial (N = 617). RESULTS: Principal-components analysis suggested
      the presence of four factors: 1) Aggressive Behavior (hitting, kicking,
      scratching, biting, pushing, grabbing, throwing things, cursing or verbal
      aggression, spitting, tearing things/destroying property, hurting self or others,
      screaming); 2) Physically Non-Aggressive Behavior (pacing, trying to get to a
      different place, general restlessness, inappropriate dressing or disrobing,
      handling things inappropriately, performing repetitious mannerisms); 3) Verbally
      Agitated Behavior (complaining, constant requests for attention, repetitive
      questions, negativism); and 4) Hiding and Hoarding. Confirmatory factor analysis
      indicated that the four-factor solution was a reasonable fit to the data.
      CONCLUSION: Four factors emerged on the CMAI in nursing home patients with
      behavioral and psychological symptoms of dementia. The results obtained converge
      reasonably with previous publications concerning the factor structure of the
      CMAI, which, taken together, suggest a fairly robust factor structure for the
      instrument.

PMID- 16286444
TI  - Development of a short form of the Severe Impairment Battery.
AB  - OBJECTIVE: The authors sought to develop a short form of the Severe Impairment
      Battery (SIB). METHODS: Authors describe the development of an empirically
      derived short form of the SIB (SIB-S) by use of data from 191 subjects with
      severe dementia in the United States and France. RESULTS: Mean (standard
      deviation) Mini-Mental State Exam scores for the American and French samples were
      7.7 (4.8) and 5.7 (3.4), respectively, and original SIB scores were 71.87 (18.34)
      and 58.38 (26.86), respectively. Exploratory factor analyses were conducted
      separately and in combination for the two samples, to determine the number of
      clinically meaningful factors. An eight-factor model, explaining 60.2% of the
      common variance, was selected. The eight constructs were described as: expressive
      language, memory (verbal and nonverbal), social interaction, color-naming,
      praxis, reading and writing, fluency, and attention. Derived SIB-S scores were
      38.41 (9.12) and 29.79 (13.17) for the American and French samples, respectively.
      CONCLUSIONS: The original SIB is a valid and reliable research tool developed to
      enable reliable assessment of patients with severe dementia; it takes
      approximately 30 minutes to administer. The SIB-S takes only 10-15 minutes to
      administer, making it more appropriate for use in patients with very severe
      dementia, while it maintains the attributes of the original SIB.

PMID- 16286445
TI  - Cortical activation during cholinesterase-inhibitor treatment in Alzheimer
      disease: preliminary findings from a pharmaco-fMRI study.
AB  - OBJECTIVE: Cholinesterase inhibitors improve cognitive functioning in Alzheimer
      disease (AD). The authors studied, with functional magnetic resonance imaging
      (fMRI), the neural mechanism by which this cholinergic enhancement improves
      memory encoding in AD over longer time periods. METHODS: Brain activation was
      measured in 10 patients with AD and 10 healthy elderly comparison subjects with
      fMRI while they were encoding novel faces. Patients were scanned again after a 10
      week open treatment with the cholinesterase-inhibitor donepezil. RESULTS:
      Neuropsychologically-tested memory performance improved during the treatment
      phase in the patients. During the encoding of novel faces, elderly comparison
      subjects showed more activation in the right fusiform gyrus than the group of AD
      patients. After a 10-week treatment with donepezil, the fusiform gyrus was also
      activated in patients, similar to the comparison group. CONCLUSIONS: The right
      fusiform gyrus is associated with the processing of faces. Cholinergic
      enhancement augments selective attention by increased selectivity of perceptual
      responses in patients with AD. This mechanism may contribute to a more efficient
      processing of the attended stimulus and thus be a mechanism underlying clinical
      improvement of cognitive functioning. These promising preliminary findings need
      to be confirmed in a larger, controlled trial in which both fMRI and attention
      measures serve as outcomes.

PMID- 16286446
TI  - Would caregivers of Alzheimer disease patients involve their relative in a
      decision to use an AD-slowing medication?
AB  - OBJECTIVES: The authors examined the factors associated with 1) caregivers'
      willingness to involve a relative with Alzheimer disease (AD) in a decision to
      use an AD-slowing treatment; and 2) how caregivers would resolve a disagreement
      over this decision with the their relative. METHODS: This was a cross-sectional
      interview study of 102 caregivers of patients with mild-to-severe-stage AD,
      enrolled in a University Memory Disorders Clinic. RESULTS: Forty-four percent of
      caregivers (45/102) said that his or her relative would participate in a decision
      to use an AD-slowing treatment. Logistic regression showed that having less
      dementia severity, being a female caregiver, and a spousal relationship were all
      associated with caregivers' involving their relative in this decision. Among the
      caregivers who said they would involve their relative, the majority said they
      would resolve disagreements over whether to use the treatment in favor of what
      the patient wanted, versus what the family wanted for the patient. Male
      caregivers were less likely to resolve disagreements in favor of the patients'
      preferences. CONCLUSION: Although most caregivers of patients in mild-to-moderate
      stages would include these patients in an AD treatment decision, certain
      caregiver characteristics, such as gender and relationship, are associated with
      not involving patients in this decision. Physicians working with dementia
      patients and their family members should take these characteristics into account
      when discussing treatment options and work with patient-caregiver dyads to
      improve the communication of preferences.

PMID- 16286447
TI  - Ecotype allelic variation in C-to-U editing extent of a mitochondrial transcript
      identifies RNA-editing quantitative trait loci in Arabidopsis.
AB  - In higher plants, RNA editing is a posttranscriptional process that converts C to
      U in organelle mRNAs. Although RNA editing in mitochondria occurs much more
      frequently than in chloroplasts, editing of exogenously supplied RNA substrates
      in vitro and in organello has shown that editing in the two organelles shares
      some common features. In particular, the 20 nucleotides upstream of the editing
      site play an important role in specifying the C to be edited. Biochemical
      approaches have allowed the identification of features of cis-sequences necessary
      for RNA editing to occur, but have failed to identify any of the components of
      the mitochondrial editing machinery. In order to implement a genetic approach for
      identification of editing factors, we have identified a polymorphism in the
      editing efficiency of a mitochondrial site between two ecotypes of Arabidopsis
      (Arabidopsis thaliana), Columbia (Col) and Landsberg erecta (Ler). In rosette
      leaves, an editing site within the ccb206 mitochondrial gene is more highly
      edited in Col than in Ler. Depending on the development stage and tissue
      analyzed, the difference in editing extent varies between the two ecotypes; for
      example, in floral buds, editing extent does not differ. Single-point regression
      analysis of the editing efficiency in a sample of recombinant inbred lines
      derived from a cross between Col and Ler allowed the identification of two
      quantitative trait loci controlling this trait. A member of the pentatricopeptide
      repeat protein family that carries a putative mitochondrial transit sequence has
      been identified near a major quantitative trait locus on chromosome 4.

PMID- 16286448
TI  - Involvement of a cell wall-associated kinase, WAKL4, in Arabidopsis mineral
      responses.
AB  - The cell wall-associated receptor kinase (WAK) and WAK-like kinase (WAKL) gene
      family members are good candidates for physical linkers that signal between the
      cell wall and the cytoplasmic compartment. Previous studies have suggested that
      while some WAK/WAKL members play a role in bacterial pathogen and heavy-metal
      aluminum responses, others are involved in cell elongation and plant development.
      Here, we report a functional role for the WAKL4 gene in Arabidopsis (Arabidopsis
      thaliana) mineral responses. Confocal microscopic studies localized WAKL4-green
      fluorescent protein fusion proteins on the cell surfaces suggesting that, like
      other WAK/WAKL proteins, WAKL4 protein is associated with the cell wall.
      Histochemical analyses of the WAKL4 promoter fused with the -glucuronidase
      reporter gene have shown that WAKL4 expression is induced by Na+, K+, Cu2+, Ni2+,
      and Zn2+. A transgenic line with a T-DNA insertion at 40-bp upstream of the WAKL4
      start codon was characterized. While the T-DNA insertion had little effect on the
      WAKL4 transcript levels under normal growth conditions, it significantly altered
      the expression patterns of WAKL4 under various conditions of mineral nutrients.
      Semiquantitative and quantitative reverse transcription-PCR analyses showed that
      the promoter impairment abolished WAKL4-induced expression by Na+, K+, Cu2+, and
      Zn2+, but not by Ni2+. Whereas the WAKL4 promoter impairment resulted in
      hypersensitivity to K+, Na+, Cu2+, and Zn2+, it conferred a better tolerance to
      toxic levels of the Ni2+ heavy metal. WAKL4 was required for the up-regulation of
      zinc transporter genes during zinc deficiency, and the WAKL4 T-DNA insertion
      resulted in a reduction of Zn2+ accumulation in shoots. A WAKL4-green fluorescent
      protein fusion gene driven by either the WAKL4 native promoter or the 35S
      constitutive promoter complemented the phenotypes. Our results suggest versatile
      roles for WAKL4 in Arabidopsis mineral nutrition responses.

PMID- 16286449
TI  - Switching the cell cycle. Kip-related proteins in plant cell cycle control.

PMID- 16286451
TI  - A novel approach for nontargeted data analysis for metabolomics. Large-scale
      profiling of tomato fruit volatiles.
AB  - To take full advantage of the power of functional genomics technologies and in
      particular those for metabolomics, both the analytical approach and the strategy
      chosen for data analysis need to be as unbiased and comprehensive as possible.
      Existing approaches to analyze metabolomic data still do not allow a fast and
      unbiased comparative analysis of the metabolic composition of the hundreds of
      genotypes that are often the target of modern investigations. We have now
      developed a novel strategy to analyze such metabolomic data. This approach
      consists of (1) full mass spectral alignment of gas chromatography (GC)-mass
      spectrometry (MS) metabolic profiles using the MetAlign software package, (2)
      followed by multivariate comparative analysis of metabolic phenotypes at the
      level of individual molecular fragments, and (3) multivariate mass spectral
      reconstruction, a method allowing metabolite discrimination, recognition, and
      identification. This approach has allowed a fast and unbiased comparative
      multivariate analysis of the volatile metabolite composition of ripe fruits of 94
      tomato (Lycopersicon esculentum Mill.) genotypes, based on intensity patterns of
      >20,000 individual molecular fragments throughout 198 GC-MS datasets. Variation
      in metabolite composition, both between- and within-fruit types, was found and
      the discriminative metabolites were revealed. In the entire genotype set, a total
      of 322 different compounds could be distinguished using multivariate mass
      spectral reconstruction. A hierarchical cluster analysis of these metabolites
      resulted in clustering of structurally related metabolites derived from the same
      biochemical precursors. The approach chosen will further enhance the
      comprehensiveness of GC-MS-based metabolomics approaches and will therefore prove
      a useful addition to nontargeted functional genomics research.

PMID- 16286450
TI  - Evolutionary expansion, gene structure, and expression of the rice wall
      associated kinase gene family.
AB  - The wall-associated kinase (WAK) gene family, one of the receptor-like kinase
      (RLK) gene families in plants, plays important roles in cell expansion, pathogen
      resistance, and heavy-metal stress tolerance in Arabidopsis (Arabidopsis
      thaliana). Through a reiterative database search and manual reannotation, we
      identified 125 OsWAK gene family members from rice (Oryza sativa) japonica cv
      Nipponbare; 37 (approximately 30%) OsWAKs were corrected/reannotated from earlier
      automated annotations. Of the 125 OsWAKs, 67 are receptor-like kinases, 28
      receptor-like cytoplasmic kinases, 13 receptor-like proteins, 12 short genes, and
      five pseudogenes. The two-intron gene structure of the Arabidopsis WAK/WAK-Likes
      is generally conserved in OsWAKs; however, extra/missed introns were observed in
      some OsWAKs either in extracellular regions or in protein kinase domains. In
      addition to the 38 OsWAKs with full-length cDNA sequences and the 11 with rice
      expressed sequence tag sequences, gene expression analyses, using tiling
      microarray analysis of the 20 OsWAKs on chromosome 10 and reverse transcription
      PCR analysis for five OsWAKs, indicate that the majority of identified OsWAKs are
      likely expressed in rice. Phylogenetic analyses of OsWAKs, Arabidopsis WAK/WAK
      Likes, and barley (Hordeum vulgare) HvWAKs show that the OsWAK gene family
      expanded in the rice genome due to lineage-specific expansion of the family in
      monocots. Localized gene duplications appear to be the primary genetic event in
      OsWAK gene family expansion and the 125 OsWAKs, present on all 12 chromosomes,
      are mostly clustered.

PMID- 16286452
TI  - Gerstmann-Straussler-Scheinker disease amyloid protein polymerizes according to
      the "dock-and-lock" model.
AB  - Prion protein (PrP) amyloid formation is a central feature of genetic and
      acquired prion diseases such as Gerstmann-Straussler-Scheinker disease (GSS) and
      variant Creutzfeldt-Jakob disease. The major component of GSS amyloid is a PrP
      fragment spanning residues approximately 82-146, which when synthesized as a
      peptide, readily forms fibrils featuring GSS amyloid. The present study employed
      surface plasmon resonance (SPR) to characterize the binding events underlying
      PrP82-146 oligomerization at the first stages of fibrillization, according to
      evidence suggesting a pathogenic role of prefibrillar oligomers rather than
      mature amyloid fibrils. We followed in real time the binding reactions occurring
      during short term (seconds) addition of PrP82-146 small oligomers (1-5-mers,
      flowing species) onto soluble prefibrillar PrP82-146 aggregates immobilized on
      the sensor surface. SPR data confirmed very efficient aggregation/elongation,
      consistent with the hypothesis of nucleation-dependent polymerization process.
      Much lower binding was observed when PrP82-146 flowed onto the scrambled sequence
      of PrP82-146 or onto prefibrillar Abeta42 aggregates. As previously found with
      Abeta40, SPR data could be adequately fitted by equations modeling the "dock-and
      lock" mechanism, in which the "locking" step is due to sequential conformational
      changes, each increasing the affinity of the monomer for the fibril until a
      condition of irreversible binding is reached. However, these conformational
      changes (i.e. the locking steps) appear to be faster and easier with PrP82-146
      than with Abeta40. Such differences suggest that PrP82-146 has a greater
      propensity to polymerize and greater stability of the aggregates.

PMID- 16286453
TI  - Three dileucine-like motifs within the interbox1/2 region of the human oncostatin
      M receptor prevent efficient surface expression in the absence of an associated
      Janus kinase.
AB  - The oncostatin M receptor (OSMR) is part of receptor complexes for oncostatin M
      and interleukin-31. Signaling events are triggered by Jaks (Janus kinases) that
      constitutively bind to membrane-proximal receptor regions. Besides their
      established role in signaling, Jaks are involved in the regulation of the surface
      expression of several cytokine receptors. Here, we analyzed the structural
      requirements within the human OSMR that underlie its limited surface expression
      in the absence of associated Jaks. We identified three dileucine-like motifs
      within the Jak-binding region of the OSMR that control receptor surface and
      overall expression. A receptor mutant in which all three motifs were mutated to
      alanine displayed markedly increased surface expression. Although the surface
      half-life of this mutant was increased compared with that of the wild-type
      receptor, no difference in the internalization rate was detectable, implying that
      these receptors differ in their post-endocytic fate. The protein stability of the
      wild-type receptor was markedly lower than that of mutant receptors, but could be
      strongly increased in the presence of the lysosomal inhibitor chloroquine. Our
      data are consistent with the dileucine motifs being involved in destabilization
      of receptors devoid of associated Jaks as part of a quality control ensuring
      signaling competence of OSMRs.

PMID- 16286454
TI  - Functional characterization of dehydratase/aminotransferase pairs from
      Helicobacter and Campylobacter: enzymes distinguishing the pseudaminic acid and
      bacillosamine biosynthetic pathways.
AB  - Helicobacter pylori and Campylobacter jejuni have been shown to modify their
      flagellins with pseudaminic acid (Pse), via O-linkage, while C. jejuni also
      possesses a general protein glycosylation pathway (Pgl) responsible for the N
      linked modification of at least 30 proteins with a heptasaccharide containing 2,4
      diacetamido-2,4,6-trideoxy-alpha-D-glucopyranose, a derivative of bacillosamine.
      To further define the Pse and bacillosamine biosynthetic pathways, we have
      undertaken functional characterization of UDP-alpha-D-GlcNAc modifying
      dehydratase/aminotransferase pairs, in particular the H. pylori and C. jejuni
      flagellar pairs HP0840/HP0366 and Cj1293/Cj1294, as well as the C. jejuni Pgl
      pair Cj1120c/Cj1121c using His(6)-tagged purified derivatives. The metabolites
      produced by these enzymes were identified using NMR spectroscopy at 500 and/or
      600 MHz with a cryogenically cooled probe for optimal sensitivity. The
      metabolites of Cj1293 (PseB) and HP0840 (FlaA1) were found to be labile and could
      only be characterized by NMR analysis directly in aqueous reaction buffer. The
      Cj1293 and HP0840 enzymes exhibited C6 dehydratase as well as a newly identified
      C5 epimerase activity that resulted in the production of both UDP-2-acetamido-2,6
      dideoxy-beta-L-arabino-4-hexulose and UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4
      hexulose. In contrast, the Pgl dehydratase Cj1120c (PglF) was found to possess
      only C6 dehydratase activity generating UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo
      4-hexulose. Substrate-specificity studies demonstrated that the flagellar
      aminotransferases HP0366 and Cj1294 utilize only UDP-2-acetamido-2,6-dideoxy-beta
      L-arabino-4-hexulose as substrate producing UDP-4-amino-4,6-dideoxy-beta-L
      AltNAc, a precursor in the Pse biosynthetic pathway. In contrast, the Pgl
      aminotransferase Cj1121c (PglE) utilizes only UDP-2-acetamido-2,6-dideoxy-alpha-D
      xylo-4-hexulose producing UDP-4-amino-4,6-dideoxy-alpha-D-GlcNAc (UDP-2-acetamido
      4-amino-2,4,6-trideoxy-alpha-D-glucopyranose), a precursor used in the production
      of the Pgl glycan component 2,4-diacetamido-2,4,6-trideoxy-alpha-D-glucopyranose.

PMID- 16286455
TI  - Glycosylation substrate specificity of Pseudomonas aeruginosa 1244 pilin.
AB  - The beta-carbon of the Pseudomonas aeruginosa 1244 pilin C-terminal Ser is a site
      of glycosylation. The present study was conducted to determine the pilin
      structures necessary for glycosylation. It was found that although Thr could be
      tolerated at the pilin C terminus, the blocking of the Ser carboxyl group with
      the addition of an Ala prevented glycosylation. Pilin from strain PA103 was not
      glycosylated by P. aeruginosa 1244, even when the C-terminal residue was
      converted to Ser. Substituting the disulfide loop region of strain PA103 pilin
      with that of strain 1244 allowed glycosylation to take place. Neither conversion
      of 1244 pilin disulfide loop Cys residues to Ala nor the deletion of segments of
      this structure prevented glycosylation. It was noted that the PA103 pilin
      disulfide loop environment was electronegative, whereas that of strain 1244 pilin
      had an overall positive charge. Insertion of a positive charge into the PA103
      pilin disulfide loop of a mutant containing Ser at the C terminus allowed
      glycosylation to take place. Extending the "tail" region of the PA103 mutant
      pilin containing Ser at its terminus resulted in robust glycosylation. These
      results suggest that the terminal Ser is the major pilin glycosylation
      recognition feature and that this residue cannot be substituted at its carboxyl
      group. Although no other specific recognition features are present, the pilin
      surface must be compatible with the reaction apparatus for glycosylation to
      occur.

PMID- 16286456
TI  - Cellular trafficking and degradation of erythropoietin and novel erythropoiesis
      stimulating protein (NESP).
AB  - Erythropoietin (Epo) is essential for the production of mature red blood cells,
      and recombinant Epo is commonly used to treat anemia, but how Epo is degraded and
      cleared from the body is not understood. Glycosylation of Epo is required for its
      in vivo bioactivity, although not for in vitro receptor binding or stimulation of
      Epo-dependent cell lines; Epo glycosylation actually reduces the affinity of Epo
      for the Epo receptor (EpoR). Interestingly, a hyperglycosylated analog of Epo,
      called novel erythropoiesis-stimulating protein (NESP), has a lower affinity than
      Epo for the EpoR but has greater in vivo activity and a longer serum half-life
      than Epo. We hypothesize that a major mechanism for degradation of Epo in the
      body occurs in cells expressing the Epo receptor, through receptor-mediated
      endocytosis of Epo followed by degradation in lysosomes, and therefore
      investigated the trafficking and degradation of Epo and NESP by EpoR-expressing
      cells. We show that Epo and NESP are degraded only by cultured cells that express
      the EpoR, and their receptor binding, dissociation, and trafficking properties
      determine their rates of intracellular degradation. Epo binds surface EpoR faster
      than NESP (k(on) = 5.0 x 10(8) m(-1) min(-1) versus 1.1 x 10(8) m(-1) min(-1))
      but dissociates slower (k(off) = 0.029 min(-1) versus 0.042 min(-1)). Surface
      bound Epo and NESP are internalized at the same rate (k(in) = 0.06 min(-1)), and
      after internalization 60% of each ligand is resecreted intact and 40% degraded.
      Our kinetic model of Epo and NESP receptor binding, intracellular trafficking,
      and degradation explains why Epo is degraded faster than NESP at the cellular
      level.

PMID- 16286457
TI  - Phosphorylation of IkappaB-beta is necessary for neuronal survival.
AB  - Cerebellar granule neurons undergo apoptosis when switched from culture medium
      containing depolarizing levels of potassium (high potassium or HK) to
      nondepolarizing medium (low potassium or LK). We showed that in healthy neurons
      maintained in HK medium, IkappaB-beta is phosphorylated at a novel site, Tyr-161.
      LK-induced neuronal apoptosis is accompanied by a decrease in the extent of
      IkappaB-beta phosphorylation at this residue. Tyr-161 shares similarity to the
      consensus sequence for phosphorylation by the nonreceptor tyrosine kinases Abl
      and Arg. Arg phosphorylates Tyr-161 differentially in vitro, and LK treatment
      does cause a down-regulation of Arg activity. Moreover, treatment of neurons with
      two structurally distinct and highly selective Abl inhibitors, PD173955 and
      Gleevec, blocks HK-induced phosphorylation of IkappaB-beta at Tyr-161 and induces
      neuronal apoptosis. Overexpression of wild-type IkappaB-beta blocks LK-induced
      apoptosis, but this effect is abolished when Arg is pharmacologically inhibited.
      On the other hand, forced overexpression of IkappaB-beta in which Tyr-161 is
      mutated inhibits survival in HK demonstrating the importance of this residue to
      neuronal survival. Phosphorylation of IkappaB-beta enhances its association with
      p65/RelA causing an increase in NF-kappaB DNA binding activity. Our results
      identified IkappaB-beta phosphorylation as a key event in neuronal survival and
      provided a mechanism by which this is mediated.

PMID- 16286458
TI  - Identification and functional expression of a family of nicotinic acetylcholine
      receptor subunits in the central nervous system of the mollusc Lymnaea stagnalis.
AB  - We described a family of nicotinic acetylcholine receptor (nAChR) subunits
      underlying cholinergic transmission in the central nervous system (CNS) of the
      mollusc Lymnaea stagnalis. By using degenerate PCR cloning, we identified 12
      subunits that display a high sequence similarity to nAChR subunits, of which 10
      are of the alpha-type, 1 is of the beta-type, and 1 was not classified because of
      insufficient sequence information. Heterologous expression of identified subunits
      confirms their capacity to form functional receptors responding to acetylcholine.
      The alpha-type subunits can be divided into groups that appear to underlie cation
      conducting (excitatory) and anion-conducting (inhibitory) channels involved in
      synaptic cholinergic transmission. The expression of the Lymnaea nAChR subunits,
      assessed by real time quantitative PCR and in situ hybridization, indicates that
      it is localized to neurons and widespread in the CNS, with the number and
      localization of expressing neurons differing considerably between subunit types.
      At least 10% of the CNS neurons showed detectable nAChR subunit expression. In
      addition, cholinergic neurons, as indicated by the expression of the vesicular
      ACh transporter, comprise approximately 10% of the neurons in all ganglia.
      Together, our data suggested a prominent role for fast cholinergic transmission
      in the Lymnaea CNS by using a number of neuronal nAChR subtypes comparable with
      vertebrate species but with a functional complexity that may be much higher.

PMID- 16286459
TI  - Zinc and calcium ions cooperatively modulate ADAMTS13 activity.
AB  - ADAMTS13 is a metalloproteinase that cleaves von Willebrand factor (VWF)
      multimers. The metal ion dependence of ADAMTS13 activity was examined with
      multimeric VWF and a fluorescent peptide substrate based on Asp(1596)-Arg(1668)
      of the VWF A2 domain, FRETS-VWF73. ADAMTS13 activity in citrate-anticoagulated
      plasma was enhanced approximately 2-fold by zinc ions, approximately 3-fold by
      calcium ions, and approximately 6-fold by both ions, suggesting cooperative
      activation. Cleavage of VWF by recombinant ADAMTS13 was activated up to
      approximately 200-fold by zinc ions (K(D) (app) approximately 0.5 microM),
      calcium ions (K(D) (app) approximately 4.8 microM), and barium ions (K(D) (app)
      approximately 1.7 mM). Barium ions stimulated ADAMTS13 activity in citrated
      plasma but not in citrate-free plasma. Therefore, the stimulation by barium ions
      of ADAMTS13 in citrated plasma appears to reflect the release of chelated calcium
      and zinc ions from complexes with citrate. At optimal zinc and calcium
      concentrations, ADAMTS13 cleaved VWF with a K(m) (app) of 3.7 +/- 1.4 microg/ml
      (approximately 15 nM for VWF subunits), which is comparable with the plasma VWF
      concentration of 5-10 microg/ml. ADAMTS13 could cleave approximately 14% of VWF
      pretreated with guanidine HCl, suggesting that this substrate is heterogeneous in
      susceptibility to proteolysis. ADAMTS13 cleaved FRETS-VWF73 with a K(m) (app) of
      3.2 +/- 1.1 microM, consistent with an approximately 200-fold decrease in
      affinity compared with VWF. ADAMTS13 cleaved VWF and FRETS-VWF73 with roughly
      comparable catalytic efficiency of 55 microM(-1) min(-1) and 18 microM(-1) min(
      1), respectively. The striking preference of ADAMTS13 for VWF suggests that
      substrate recognition depends on structural features or exosites on multimeric
      VWF that are missing from FRETS-VWF73.

PMID- 16286460
TI  - The preventive effect of salvianolic acid B on malignant transformation of DMBA
      induced oral premalignant lesion in hamsters.
AB  - Salvia miltiorrhiza (SM) has been used clinically in Asian countries to improve
      the microcirculation in the human body. Salvianolic acid B (Sal B), a pure
      compound extracted from SM, has been reported to be effective against fibrosis
      and ischemia-reperfusion injury, possibly through its anti-lipid peroxidation
      action. But the effect of Sal B on oral premalignant lesion and oral
      carcinogenesis remains unexplored. It is our interest to investigate the
      chemopreventive effect of Sal B on 7,12-dimethylbenz[a]anthracene (DMBA)-induced
      oral carcinogenesis in hamsters with respect to angiogenesis. Seventy male Syrian
      golden hamsters were randomly divided into five groups, with two of 20 and three
      of 10. DMBA solution (0.5% in acetone) was applied topically to the left cheek
      pouch of male Syrian golden hamsters in Groups A and B, while animals in Group C
      were painted with acetone, three times a week for 6 weeks. For the next 18 weeks,
      animals in Groups B and D received Sal B daily (10 mg/kg body wt/day) by gavage,
      animals in Groups A and C received same volume of saline. Animals in Group E
      received no treatment and served as blank control. At the end of the experiment,
      animals were killed and tissue samples were collected for histopathological and
      immunohistochemical examinations. The results showed that Sal B significantly
      decreased the squamous cell carcinoma (SCC) incidence from 64.7 (11/17) to 16.7%
      (3/18) (P=0.004); angiogenesis was inhibited in dysplasia and SCC (P<0.01), with
      a simultaneous decrease in the immunostaining of hypoxia-inducible factor 1alpha
      and vascular endothelium growth factor protein (P<0.05). The results suggested
      that Sal B had inhibitory effect against the malignant transformation of oral
      precancerous lesion and such inhibition may be related to the inhibition of
      angiogenesis.

PMID- 16286461
TI  - Conjugated linoleic acid stimulates an anti-tumorigenic protein NAG-1 in an
      isomer specific manner.
AB  - Conjugated linoleic acids (CLAs), naturally occurring fatty acids in ruminant
      food products, have anti-tumorigenic and pro-apoptotic properties in animal as
      well as in vitro models of cancer. However, the cellular mechanism has not been
      fully understood. NAG-1 (non-steroidal anti-inflammatory drug-activated gene-1)
      is induced by several dietary compounds and belongs to a TGF-beta superfamily
      gene associated with pro-apoptotic and anti-tumorigenic activities. The present
      study was performed to elucidate the molecular mechanism by which CLA stimulates
      anti-tumorigenic activity in human colorectal cancer (CRC) cells. The trans-10,
      cis-12-CLA (t10,c12-CLA) repressed cell proliferation and induced apoptosis,
      whereas linoleic acid or c9,t11-CLA showed no effect on cell proliferation and
      apoptosis. We also found that t10,c12-CLA induced the expression of a pro
      apoptotic gene, NAG-1, in human CRC cells. Inhibition of NAG-1 expression by
      small interference RNA (siRNA) results in repression of t10,c12-CLA-induced
      apoptosis. Microarray analysis using t10,c12-CLA-treated HCT-116 cells revealed
      that activating transcription factor 3 (ATF3) was induced and its expression was
      confirmed by western analysis. The t10,c12-CLA treatment followed by the
      overexpression of ATF3 increased NAG-1 promoter activity in HCT-116 cells. We
      further provide the evidence that t10,c12-CLA inhibited the phosphorylation of
      AKT and the blockage of GSK-3 by siRNA abolished t10,c12-CLA-induced ATF3 and NAG
      1 expression. The current study demonstrates that t10,c12-CLA stimulates ATF3/NAG
      1 expression and subsequently induces apoptosis in an isomer specific manner.
      These effects may be through inhibition of AKT/GSK-3beta pathway in human CRC
      cells.

PMID- 16286462
TI  - Pathways to the diagnosis of colorectal cancer: an observational study in three
      UK cities.
AB  - BACKGROUND: Colorectal cancer can present in a variety of ways, and with any of
      several symptoms. Different referral routes from primary to secondary care cater
      for these different presentations. The route that has received most investment in
      the UK National Health Service is the 2-week clinic, but the proportions of
      patients taking this and other routes to diagnosis are largely unknown. METHODS:
      We designed an observational audit in Exeter, Oxford and Sheffield, UK.
      Colorectal cancers diagnosed in 2002 from participating practices were identified
      and the presence and timing of seven important clinical features noted:
      diarrhoea, constipation, rectal bleeding, abdominal pain, the finding of an
      abdominal or rectal mass on examination, anaemia and positive faecal occult blood
      tests. The referral pathways to secondary care were identified. RESULTS: Of the
      151 patients studied, 112 (74%) were referred with at least one clinical feature
      of colorectal cancer to a specialist. Only 43 of these (28% of the total) were
      referred to a 2-week clinic; 39 patients (26% of the total) had an emergency
      admission, of whom 10 (7%) had their emergency admission after referral to a
      specialist for investigation but before a diagnosis had been established. The
      time intervals between the first consultation with a symptom of cancer and
      referral were mostly short. CONCLUSION: Patients with colorectal cancer travel
      several different pathways to diagnosis. The pathway with the most resources-the
      2-week clinic-is used by a minority of patients.

PMID- 16286463
TI  - Acute cooling of the feet and the onset of common cold symptoms.
AB  - BACKGROUND: There is a common folklore that chilling of the body surface causes
      the development of common cold symptoms, but previous clinical research has
      failed to demonstrate any effect of cold exposure on susceptibility to infection
      with common cold viruses. OBJECTIVE: This study will test the hypothesis that
      acute cooling of the feet causes the onset of common cold symptoms. METHODS: 180
      healthy subjects were randomized to receive either a foot chill or control
      procedure. All subjects were asked to score common cold symptoms, before and
      immediately after the procedures, and twice a day for 4/5 days. RESULTS: 13/90
      subjects who were chilled reported they were suffering from a cold in the 4/5
      days after the procedure compared to 5/90 control subjects (P=0.047). There was
      no evidence that chilling caused any acute change in symptom scores (P=0.62).
      Mean total symptom score for days 1-4 following chilling was 5.16 (+/-5.63 s.d.
      n=87) compared to a score of 2.89 (+/-3.39 s.d. n=88) in the control group
      (P=0.013). The subjects who reported that they developed a cold (n=18) reported
      that they suffered from significantly more colds each year (P=0.007) compared to
      those subjects who did not develop a cold (n=162). CONCLUSION: Acute chilling of
      the feet causes the onset of common cold symptoms in around 10% of subjects who
      are chilled. Further studies are needed to determine the relationship of symptom
      generation to any respiratory infection.

PMID- 16286464
TI  - Neuroendocrine protein 7B2 can be inactivated by phosphorylation within the
      secretory pathway.
AB  - The prohormone convertases play important roles in the maturation of
      neuropeptides and peptide hormone precursors. Prohormone convertase-2 (PC2) is
      the only convertase that requires the expression of another neuroendocrine
      protein, 7B2, for expression of enzyme activity. In this study, we determined
      that 7B2 can be phosphorylated in Rin cells (a rat insulinoma cell line) and
      cultured chromaffin cells, but not in AtT-20 cells (derived from mouse anterior
      pituitary). Phosphoamino acid analysis of Rin cell 7B2 indicated the presence of
      phosphorylated serine and threonine. Phosphorylation of Ser115 (located within
      the minimally active 36-residue peptide) was confirmed by mutagenesis, although
      Ser115 did not represent the sole residue phosphorylated. Two independent assays
      were used to investigate the effect of phosphorylated 7B2 on PC2 activation: the
      ability of 7B2 to bind to pro-PC2 was assessed by co-immunoprecipitation, and
      activation of pro-PC2 was assessed in a cell-free assay. Phosphorylated 7B2 was
      unable to bind pro-PC2, and the phosphorylated 7B2 peptide (residues 86-121,
      known to be the minimally active peptide for pro-PC2 activation) was impaired in
      its ability to facilitate the generation of PC2 activity in membrane fractions
      containing pro-PC2. In vitro phosphorylation experiments using Golgi membrane
      fractions showed that 7B2 could be phosphorylated by endogenous Golgi kinases.
      Golgi kinase activity was strongly inhibited by the broad-range kinase inhibitor
      staurosporine and partially inhibited by the protein kinase C inhibitor
      bisindolylmaleimide I, but not by the other protein kinase A, Ca2+/calmodulin
      dependent kinase II, myosin light chain kinase, and protein kinase G inhibitors
      tested. We conclude that phosphorylation of 7B2 functionally inactivates this
      protein and suggest that this may be analogous to the phosphorylating
      inactivation of BiP, which impairs its ability to bind substrate.

PMID- 16286465
TI  - The FtsH protease slr0228 is important for quality control of photosystem II in
      the thylakoid membrane of Synechocystis sp. PCC 6803.
AB  - The cyanobacterium Synechocystis sp. PCC 6803 contains four members of the FtsH
      protease family. One of these, FtsH (slr0228), has been implicated recently in
      the repair of photodamaged photosystem II (PSII) complexes. We have demonstrated
      here, using a combination of blue native PAGE, radiolabeling, and immunoblotting,
      that FtsH (slr0228) is required for selective replacement of the D1 reaction
      center subunit in both wild type PSII complexes and in PSII subcomplexes lacking
      the PSII chlorophyll a-binding subunit CP43. To test whether FtsH (slr0228) has a
      more general role in protein quality control in vivo, we have studied the
      synthesis and degradation of PSII subunits in wild type and in defined insertion
      and missense mutants incapable of proper assembly of the PSII holoenzyme. We
      discovered that, when the gene encoding FtsH (slr0228) was disrupted in these
      strains, the overall level of assembly intermediates and unassembled PSII
      proteins markedly increased. Pulse-chase experiments showed that this was due to
      reduced rates of degradation in vivo. Importantly, analysis of epitope-tagged and
      green fluorescent protein-tagged strains revealed that slr0228 was present in the
      thylakoid and not the cytoplasmic membrane. Overall, our results show that FtsH
      (slr0228) plays an important role in controlling the removal of PSII subunits
      from the thylakoid membrane and is not restricted to selective D1 turnover.

PMID- 16286466
TI  - Caspases target only two architectural components within the core structure of
      the nuclear pore complex.
AB  - Caspases were recently implicated in the functional impairment of the nuclear
      pore complex during apoptosis, affecting its dual activity as nucleocytoplasmic
      transport channel and permeability barrier. Concurrently, electron microscopic
      data indicated that nuclear pore morphology is not overtly altered in apoptotic
      cells, raising the question of how caspases may deactivate nuclear pore function
      while leaving its overall structure largely intact. To clarify this issue we have
      analyzed the fate of all known nuclear pore proteins during apoptotic cell death.
      Our results show that only two of more than 20 nuclear pore core structure
      components, namely Nup93 and Nup96, are caspase targets. Both proteins are
      cleaved near their N terminus, disrupting the domains required for interaction
      with other nucleoporins actively involved in transport and providing the
      permeability barrier but dispensable for maintaining the nuclear pore scaffold.
      Caspase-mediated proteolysis of only few nuclear pore complex components may
      exemplify a general strategy of apoptotic cells to efficiently disable huge
      macromolecular machines.

PMID- 16286467
TI  - Interleukin-1beta induction of NFkappaB is partially regulated by H2O2-mediated
      activation of NFkappaB-inducing kinase.
AB  - Reactive oxygen species (ROS) have been demonstrated to act as second messengers
      in a number of signal transduction pathways, including NFkappaB. However, the
      mechanism(s) by which ROS regulate NFkappaB remain unclear and controversial. In
      the present report, we describe a mechanism whereby interleukin-1beta (IL-1beta)
      stimulation of NFkappaB is partially regulated by H2O2-mediated activation of NIK
      and subsequent NIK-mediated phosphorylation of IKKalpha. IL-1beta induced H2O2
      production in MCF-7 cells and clearance of this ROS through the expression of GPx
      1 reduced NFkappaB transcriptional activation by inhibiting NIK-mediated
      phosphorylation of IKKalpha. Although IKKalpha and IKKbeta were both involved in
      IL-1beta-mediated activation of NFkappaB, only the IKKalpha-dependent component
      was modulated by changes in H2O2 levels. Interestingly, in vitro reconstitution
      experiments demonstrated that NIK was activated by a very narrow range of H2O2 (1
      10 microM), whereas higher concentrations (100 microM to 1 mM) inhibited NIK
      activity. Treatment of cells with the general Ser/Thr phosphatase inhibitor
      (okadaic acid) lead to activation of NFkappaB and enhanced NIK activity as a
      IKKalpha kinase, suggesting that ROS may directly regulate NIK through the
      inhibition of phosphatases. Recruitment of NIK to TRAF6 following IL-1beta
      stimulation was inhibited by H2O2 clearance and Rac1 siRNA, suggesting that Rac
      dependent NADPH oxidase may be a source of ROS required for NIK activation. In
      summary, our studies have demonstrated that redox regulation of NIK by H2O2 is
      mechanistically important in IL-1beta induction of NFkappaB activation.

PMID- 16286469
TI  - Overexpression of leucyl aminopeptidase in Plasmodium falciparum parasites.
      Target for the antimalarial activity of bestatin.
AB  - Malaria aminopeptidases are important in the generation and regulation of free
      amino acids that are used in protein anabolism and for maintaining osmotic
      stability within the infected erythrocyte. The intraerythrocytic development of
      malaria parasites is blocked when the activity of aminopeptidases is specifically
      inhibited by reagents such as bestatin. One of the major aminopeptidases of
      malaria parasites is a leucyl aminopeptidase of the M17 family. We reasoned that,
      when this enzyme was the target of bestatin inhibition, its overexpression in
      malaria cells would lead to a reduced sensitivity to the inhibitor. To address
      this supposition, transgenic Plasmodium falciparum parasites overexpressing the
      leucyl aminopeptidase were generated by transfection with a plasmid that housed
      the full-length gene. Transgenic parasites expressed a 65-kDa protein close to
      the predicted molecule size of 67.831 kDa for the introduced leucyl
      aminopeptidase, and immunofluorescence studies localized the protein to the
      cytosol, the location of the native enzyme. The product of the transgene was
      shown to be functionally active with cytosolic extracts of transgenic parasites
      exhibiting twice the leucyl aminopeptidase activity compared with wild-type
      parasites. In vitro inhibitor sensitivity assays demonstrated that the transgenic
      parasites were more resistant to bestatin (EC50 64 microM) compared with the
      parent parasites (EC50 25 microM). Overexpression of genes in malaria parasites
      would have general application in the identification and validation of targets
      for antimalarial drugs.

PMID- 16286468
TI  - Effects of stable suppression of Group VIA phospholipase A2 expression on
      phospholipid content and composition, insulin secretion, and proliferation of INS
      1 insulinoma cells.
AB  - Studies involving pharmacologic inhibition or transient reduction of Group VIA
      phospholipase A2 (iPLA2beta) expression have suggested that it is a housekeeping
      enzyme that regulates cell 2-lysophosphatidylcholine (LPC) levels, rates of
      arachidonate incorporation into phospholipids, and degradation of excess
      phosphatidylcholine (PC). In insulin-secreting islet beta-cells and some other
      cells, in contrast, iPLA2beta signaling functions have been proposed. Using
      retroviral vectors, we prepared clonal INS-1 beta-cell lines in which iPLA2beta
      expression is stably suppressed by small interfering RNA. Two such iPLA2beta
      knockdown (iPLA2beta-KD) cell lines express less than 20% of the iPLA2beta of
      control INS-1 cell lines. The iPLA2beta-KD INS-1 cells exhibit impaired insulin
      secretory responses and reduced proliferation rates. Electrospray ionization mass
      spectrometric analyses of PC and LPC species that accumulate in INS-1 cells
      cultured with arachidonic acid suggest that 18:0/20:4-glycerophosphocholine (GPC)
      synthesis involves sn-2 remodeling to yield 16:0/20:4-GPC and then sn-1
      remodeling via a 1-lyso/20:4-GPC intermediate. Electrospray ionization mass
      spectrometric analyses also indicate that the PC and LPC content and composition
      of iPLA2beta-KD and control INS-1 cells are nearly identical, as are the rates of
      arachidonate incorporation into PC and the composition and remodeling of other
      phospholipid classes. These findings indicate that iPLA2beta plays signaling or
      effector roles in beta-cell secretion and proliferation but that stable
      suppression of its expression does not affect beta-cell GPC lipid content or
      composition even under conditions in which LPC is being actively consumed by
      conversion to PC. This calls into question the generality of proposed
      housekeeping functions for iPLA2beta in PC homeostasis and remodeling.

PMID- 16286471
TI  - NarJ chaperone binds on two distinct sites of the aponitrate reductase of
      Escherichia coli to coordinate molybdenum cofactor insertion and assembly.
AB  - Understanding when and how metal cofactor insertion occurs into a multisubunit
      metalloenzyme is of fundamental importance. Molybdenum cofactor insertion is a
      tightly controlled process that involves specific interactions between the
      proteins that promote cofactor delivery, enzyme-specific chaperones, and the
      apoenzyme. In the assembly pathway of the multisubunit molybdoenzyme, membrane
      bound nitrate reductase A from Escherichia coli, a NarJ-assisted molybdenum
      cofactor (Moco) insertion step, must precede membrane anchoring of the apoenzyme.
      Here, we have shown that the NarJ chaperone interacts at two distinct binding
      sites of the apoenzyme, one interfering with its membrane anchoring and another
      one being involved in molybdenum cofactor insertion. The presence of the two NarJ
      binding sites within NarG is required to ensure productive formation of active
      nitrate reductase. Our findings supported the view that enzyme-specific
      chaperones play a central role in the biogenesis of multisubunit molybdoenzymes
      by coordinating subunits assembly and molybdenum cofactor insertion.

PMID- 16286470
TI  - Cooperation of ERK and SCFSkp2 for MKP-1 destruction provides a positive feedback
      regulation of proliferating signaling.
AB  - The dual-specificity MAPK phosphatase MKP-1/CL100/DUSP1 is an inducible nuclear
      protein controlled by p44/42 MAPK (ERK1/2) in a negative feedback mechanism to
      inhibit kinase activity. Here, we report on the molecular basis for a novel
      positive feedback mechanism to sustain ERK activation by triggering MKP-1
      proteolysis. Active ERK2 docking to the DEF motif (FXFP, residues 339-342) of N
      terminally truncated MKP-1 in vitro initiated phosphorylation at the
      Ser(296)/Ser(323) domain, which was not affected by substituting Ala for Ser at
      Ser(359)/Ser(364). The DEF and Ser(296)/Ser(323) sites were essential for
      ubiquitin-mediated MKP-1 proteolysis stimulated by MKK1-ERK signaling in H293
      cells, whereas the N-terminal domain and Ser(359)/Ser(364) sites were
      dispensable. ERK activation by serum increased the endogenous level of
      ubiquitinated phospho-Ser(296) MKP-1 and the degradation of MKP-1. Intriguingly,
      active ERK-promoted phospho-Ser(296) MKP-1 bound to SCF(Skp2) ubiquitin ligase in
      vivo and in vitro. Forced expression of Skp2 enhanced MKP-1 polyubiquitination
      and proteolysis upon ERK activation, whereas depletion of endogenous Skp2
      suppressed such events. The kinetics of ERK signaling stimulated by serum
      correlated with the endogenous MKP-1 degradation rate in a Skp2-dependent manner.
      Thus, MKP-1 proteolysis can be achieved via ERK and SCF(Skp2) cooperation,
      thereby sustaining ERK activation.

PMID- 16286472
TI  - Rad3-Cds1 mediates coupling of initiation of meiotic recombination with DNA
      replication. Mei4-dependent transcription as a potential target of meiotic
      checkpoint.
AB  - Premeiotic S-phase and meiotic recombination are known to be strictly coupled in
      Saccharomyces cerevisiae. However, the checkpoint pathway regulating this
      coupling has been largely unknown. In fission yeast, Rad3 is known to play an
      essential role in coordination of DNA replication and cell division during both
      mitotic growth and meiosis. Here we have examined whether the Rad3 pathway also
      regulates the coupling of DNA synthesis and recombination. Inhibition of
      premeiotic S-phase with hydroxyurea completely abrogates the progression of
      meiosis, including the formation of DNA double-strand breaks (DSBs). DSB
      formation is restored in rad3 mutant even in the presence of hydroxyurea,
      although repair of DSBs does not take place or is significantly delayed,
      indicating that the subsequent recombination steps may be still inhibited.
      Examination of the roles of downstream checkpoint kinases reveals that Cds1, but
      not Chk1 or Mek1, is required for suppression of DSB in the presence of
      hydroxyurea. Transcriptional induction of some rec+ genes essential for DSB
      occurs at a normal timing and to a normal level in the absence of DNA synthesis
      in both the wild-type and cds1delta cells. On the other hand, the transcriptional
      induction of the mei4+ transcription factor and cdc25+ phosphatase, which is
      significantly suppressed by hydroxyurea in the wild-type cells, occurs almost to
      a normal level in cds1delta cells even in the presence of hydroxyurea. These
      results show that the Rad3-Cds1 checkpoint pathway coordinates initiation of
      meiotic recombination and meiotic cell divisions with premeiotic DNA synthesis.
      Because mei4+ is known to be required for DSB formation and cdc25+ is required
      for activation of meiotic cell divisions, we propose an intriguing possibility
      that the Rad3-Cds1 meiotic checkpoint pathway may target transcription of these
      factors.

PMID- 16286473
TI  - The retinoblastoma family proteins bind to and activate diacylglycerol kinase
      zeta.
AB  - The retinoblastoma protein (pRB) is a tumor suppressor and key regulator of the
      cell cycle. We have previously shown that pRB interacts with phosphatidylinositol
      4-phosphate 5-kinases, lipid kinases that can regulate phosphatidylinositol 4,5
      bisphosphate levels in the nucleus. Here, we investigated pRB binding to another
      lipid kinase in the phosphoinositide cycle, diacylglycerol kinase (DGK) that
      phosphorylates the second messenger diacylglycerol to yield phosphatidic acid. We
      found that DGKzeta, but not DGKalpha or DGK, interacts with pRB in vitro and in
      vivo. Binding of DGKzeta to pRB is dependent on the phosphorylation status of
      pRB, since only hypophosphorylated pRB interacts with DGKzeta. DGKzeta also binds
      to the pRB-related pocket proteins p107 and p130 in vitro and in cells. Although
      DGKzeta did not affect the ability of pRB to regulate E2F-mediated transcription,
      we found that pRB, p107, and p130 potently stimulate DGKzeta activity in vitro.
      Finally, overexpression of DGKzeta in pRB-null fibroblasts reconstitutes a cell
      cycle arrest induced by gamma-irradiation. These results suggest that DGKzeta may
      act in vivo as a downstream effector of pRB to regulate nuclear levels of
      diacylglycerol and phosphatidic acid.

PMID- 16286474
TI  - Structure and carboxyl-terminal domain (CTD) binding of the Set2 SRI domain that
      couples histone H3 Lys36 methylation to transcription.
AB  - During mRNA elongation, the SRI domain of the histone H3 methyltransferase Set2
      binds to the phosphorylated carboxyl-terminal domain (CTD) of RNA polymerase II.
      The solution structure of the yeast Set2 SRI domain reveals a novel CTD-binding
      fold consisting of a left-handed three-helix bundle. NMR titration shows that the
      SRI domain binds an Ser2/Ser5-phosphorylated CTD peptide comprising two
      heptapeptide repeats and three flanking NH2-terminal residues, whereas a single
      CTD repeat is insufficient for binding. Residues that show strong chemical shift
      perturbations upon CTD binding cluster in two regions. Both CTD tyrosine side
      chains contact the SRI domain. One of the tyrosines binds in the region with the
      strongest chemical shift perturbations, formed by the two NH2-terminal helices.
      Unexpectedly, the SRI domain fold resembles the structure of an RNA polymerase
      interacting domain in bacterial sigma factors (domain sigma2 in sigma70).

PMID- 16286475
TI  - Subcellular targeting and differential S-nitrosylation of endothelial nitric
      oxide synthase.
AB  - Endothelial nitric-oxide synthase (eNOS) undergoes a complex pattern of post
      translational modifications that regulate its activity. We have recently reported
      that eNOS is constitutively S-nitrosylated in endothelial cells and that agonists
      promote eNOS denitrosylation concomitant with enzyme activation (Erwin, P. A.,
      Lin, A. J., Golan, D. E., and Michel, T. (2005), J. Biol. Chem. 280, 19888
      19894). In the present studies, we use mass spectrometry to confirm that the zinc
      tetrathiolate cysteines of eNOS are S-nitrosylated. eNOS targeting to the plasma
      membrane is necessary for enzyme S-nitrosylation, and we report that
      translocation between cellular compartments is necessary for dynamic eNOS S
      nitrosylation. We transfected cells with cDNA encoding wild-type eNOS, which is
      membrane-targeted, or with acylation-deficient mutant eNOS (Myr-), which is
      expressed solely in the cytosol. While wild-type eNOS is robustly S-nitrosylated,
      we found that S-nitrosylation of the Myr- eNOS mutant is nearly abolished. When
      we transfected cells with a fusion protein in which Myr- eNOS is ligated to the
      CD8-transmembrane domain (CD8-Myr-), we found that CD8-Myr- eNOS, which does not
      undergo dynamic subcellular translocation, is hypernitrosylated relative to wild
      type eNOS. Furthermore, we found that when endothelial cells transfected with
      wild-type or CD8-Myr- eNOS are stimulated with eNOS agonist, only wild-type eNOS
      is denitrosylated; CD8-Myr- eNOS S-nitrosylation is unchanged. These findings
      indicate that subcellular targeting is a critical determinant of eNOS S
      nitrosylation. Finally, we show that eNOS S-nitrosylation can be detected in
      intact arterial preparations from mouse and that eNOS S-nitrosylation is a
      dynamic agonist-modulated process in intact blood vessels. These studies suggest
      that receptor-regulated eNOS S-nitrosylation may represent an important
      determinant of NO-dependent signaling in the vascular wall.

PMID- 16286476
TI  - Alkaline-shifted pHo sensitivity of AE2c1-mediated anion exchange reveals novel
      regulatory determinants in the AE2 N-terminal cytoplasmic domain.
AB  - The mouse anion exchanger AE2/SLC4A2 Cl(-)/HCO(-)(3) exchanger is essential to
      post-weaning life. AE2 polypeptides regulate pH(i), chloride concentration, cell
      volume, and transepithelial ion transport in many tissues. Although the AE2a
      isoform has been extensively studied, the function and regulation of the other
      AE2 N-terminal variant mRNAs of mouse (AE2b1, AE2b2, AE2c1, and AE2c2) have not
      been examined. We now present an extended analysis of AE2 variant mRNA tissue
      distribution and function. We show in Xenopus oocytes that all AE2 variant
      polypeptides except AE2c2 mediated Cl(-) transport are subject to inhibition by
      acidic pH(i) and to activation by hypertonicity and NH(+)(4). However, AE2c1
      differs from AE2a, AE2b1, and AE2b2 in its alkaline-shifted pH(o)((50)) (7.70 +/-
      0.11 versus 6.80 +/- 0.05), suggesting the presence of a novel AE2a pH-sensitive
      regulatory site between amino acids 99 and 198. Initial N-terminal deletion
      mutagenesis restricted this site to the region between amino acids 120 and 150.
      Further analysis identified AE2a residues 127-129, 130-134, and 145-149 as
      jointly responsible for the difference in pH(o)((50)) between AE2c1 and the
      longer AE2a, AE2b1, and AE2b2 polypeptides. Thus, AE2c1 exhibits a unique pH(o)
      sensitivity among the murine AE2 variant polypeptides, in addition to a unique
      tissue distribution. Physiological coexpression of AE2c1 with other AE2 variant
      polypeptides in the same cell should extend the range over which changing pH(o)
      can regulate AE2 transport activity.

PMID- 16286477
TI  - The differentiation-dependent desmosomal cadherin desmoglein 1 is a novel caspase
      3 target that regulates apoptosis in keratinocytes.
AB  - Although a number of cell adhesion proteins have been identified as caspase
      substrates, the potential role of differentiation-specific desmosomal cadherins
      during apoptosis has not been examined. Here, we demonstrate that UV-induced
      caspase cleavage of the human desmoglein 1 cytoplasmic tail results in distinct
      17- and 140- kDa products, whereas metalloproteinase-dependent shedding of the
      extracellular adhesion domain generates a 75-kDa product. In vitro studies
      identify caspase-3 as the preferred enzyme that cleaves desmoglein 1 within its
      unique repeating unit domain at aspartic acid 888, part of a consensus sequence
      not conserved among the other desmosomal cadherins. Apoptotic processing leads to
      decreased cell surface expression of desmoglein 1 and re-localization of its C
      terminus diffusely throughout the cytoplasm over a time course comparable with
      the processing of other desmosomal proteins and cytoplasmic keratins.
      Importantly, whereas classic cadherins have been reported to promote cell
      survival, short hairpin RNA-mediated suppression of desmoglein 1 in
      differentiated keratinocytes protected cells from UV-induced apoptosis.
      Collectively, our results identify desmoglein 1 as a novel caspase and
      metalloproteinase substrate whose cleavage likely contributes to the dismantling
      of desmosomes during keratinocyte apoptosis and also reveal desmoglein 1 as a
      previously unrecognized regulator of apoptosis in keratinocytes.

PMID- 16286478
TI  - A single amino acid substitution in the activation loop defines the decoy
      characteristic of VEGFR-1/FLT-1.
AB  - VEGFR-1 is a kinase-defective receptor tyrosine kinase (RTK) and negatively
      modulates angiogenesis by acting as a decoy receptor. The decoy characteristic of
      VEGFR-1 is required for normal development and angiogenesis. To date, there is no
      molecular explanation for this unusual characteristic of VEGFR-1. Here we show
      that the molecular mechanisms underlying the decoy characteristic of VEGFR-1 is
      linked to the replacement of a highly conserved amino acid residue in the
      activation loop. This amino acid is highly conserved among all the type III RTKs
      and corresponds to aspartic acid, but in VEGFR-1 it is substituted to asparagine.
      Mutation of asparagine (Asn(1050)) within the activation loop to aspartic acid
      promoted enhanced ligand-dependent tyrosine autophosphorylation and kinase
      activation in vivo and in vitro. The mutant VEGFR-1 (Asp(1050)) promoted
      endothelial cell proliferation but not tubulogenesis. It also displayed an
      oncogenic phenotype as its expression in fibroblast cells elicited transformation
      and colony growth. Furthermore, mutation of the invariable aspartic acid to
      asparagine in VEGFR-2 lowered the autophosphorylation of activation loop
      tyrosines 1052 and 1057. We propose that the conserved aspartic acid in the
      activation loop favors the transphosphorylation of the activation loop tyrosines,
      and its absence renders RTK to a less potent enzyme by disfavoring
      transphosphorylation of activation loop tyrosines.

PMID- 16286479
TI  - Fibroblast growth factor-2 is a downstream mediator of phosphatidylinositol 3
      kinase-Akt signaling in 14,15-epoxyeicosatrienoic acid-induced angiogenesis.
AB  - To determine the efficacy of cytochrome P450 2C9 metabolites of arachidonic acid,
      viz. 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EETs), in inducing
      angiogenesis, we have studied their effects on human dermal microvascular
      endothelial cell (HDMVEC) tube formation and migration. All four EETs stimulated
      HDMVEC tube formation and migration in a dose-dependent manner. Because 14,15-EET
      was found to be slightly more efficacious than 5,6-, 8,9-, and 11,12-EETs in
      stimulating HDMVEC tube formation and migration, we next focused on elucidation
      of the signaling mechanisms underlying its angiogenic activity. 14,15-EET
      stimulated Akt and S6K1 phosphorylation in Src- and phosphatidylinositol 3-kinase
      (PI3K)-dependent manner in HDMVECs. Inhibition of Src and PI3K-Akt-mTOR signaling
      by both pharmacological and dominant-negative mutant approaches suppressed 14,15
      EET-induced HDMVEC tube formation and migration in vitro and Matrigel plug
      angiogenesis in vivo. In addition, 14,15-EET induced the expression of fibroblast
      growth factor-2 (FGF-2) in Src- and PI3K-Akt-dependent and mTOR-independent
      manner in HDMVECs. Neutralizing anti-FGF-2 antibodies completely suppressed 14,15
      EET-induced HDMVEC tube formation and migration in vitro and Matrigel plug
      angiogenesis in vivo. Together, these results show for the first time that Src
      and PI3K-Akt signaling via targeting in parallel with FGF-2 expression and mTOR
      S6K1 activation plays an indispensable role in 14,15-EET-induced angiogenesis.

PMID- 16286480
TI  - Anti-tobacco television advertising and indicators of smoking cessation in
      adults: a cohort study.
AB  - The objective of this study was to assess the relationship between exposure to
      state-sponsored anti-tobacco advertising and smoking cessation. Cessation rates
      in 2001 among a cohort of 2061 smokers who participated in the Community
      Intervention Trial for Smoking Cessation between 1988 and 1993 and completed a
      follow-up survey in 2001 were merged with the 2000-01 television advertising
      exposure data from Nielsen Media Research. The relative risk for quitting was
      estimated to be 10% higher for every 5000 units of exposure to state anti-tobacco
      television advertising over the 2-year period, although this did not quite
      achieve statistical significance. The association was even larger among those who
      reported that the level of information in the media about the dangers of smoking
      had increased 'a lot' between 1993 and 2001 (RR = 1.19, 95% CI = 1.03-1.38).
      These data are consistent with the finding that increased exposure to state anti
      tobacco media increases smoking cessation rates.

PMID- 16286481
TI  - Salmonella-infected left ventricular thrombus.

PMID- 16286482
TI  - A 1 year surveillance study of glycopeptide-intermediate Staphylococcus aureus
      strains in a French hospital.
AB  - OBJECTIVES: Glycopeptides are the drugs of choice to treat infections due to
      methicillin-resistant Staphylococcus aureus, but since 1995, glycopeptide
      intermediate S. aureus (GISA) and heterogeneous GISA (hGISA) have been reported
      worldwide. Detection of reduced susceptibility to glycopeptides in S. aureus is
      very difficult in a routine clinical laboratory. The aim of this study was to
      investigate the prevalence of hGISA/GISA strains using a three-step approach
      during a 1 year period. METHODS: The following algorithm was adopted: (i) brain
      heart infusion agar with 4 mg/L teicoplanin was used to screen S. aureus strains
      for reduced susceptibility to glycopeptides; (ii) for each agar screen-positive
      strain, an Etest macromethod using modified cut-off values (vancomycin and
      teicoplanin > or =4 mg/L) was used to detect potential hGISA/GISA; and (iii) the
      population analysis profile (PAP) method was finally used to confirm the
      hGISA/GISA phenotype. RESULTS: In total, 2300 strains of S. aureus were screened
      and 255 (11%) were categorized as hGISA with the PAP method, whereas no GISA
      strains were detected. Standard MIC values and current MIC breakpoints could not
      discriminate the hGISA/GISA phenotype from glycopeptide-susceptible S. aureus.
      Thus laboratories using currently standardized MIC methods cannot be expected to
      detect S. aureus strains that may exhibit reduced susceptibility to
      glycopeptides. Molecular typing by PFGE revealed that 238 strains belonged to the
      same clone. CONCLUSIONS: A clonal hGISA strain has disseminated within our
      hospital. The method described in this study has to be further investigated to
      see if it is applicable to other S. aureus strains.

PMID- 16286483
TI  - Choosing or losing health?

PMID- 16286484
TI  - Conceptual diagrams in public health research.

PMID- 16286485
TI  - Negro, Black, Black African, African Caribbean, African American or what?
      Labelling African origin populations in the health arena in the 21st century.
AB  - Broad terms such as Black, African, or Black African are entrenched in scientific
      writings although there is considerable diversity within African descent
      populations and such terms may be both offensive and inaccurate. This paper
      outlines the heterogeneity within African populations, and discusses the
      strengths and limitations of the term Black and related labels from
      epidemiological and public health perspectives in Europe and the USA. This paper
      calls for debate on appropriate terminologies for African descent populations and
      concludes with the proposals that (1) describing the population under
      consideration is of paramount importance (2) the word African origin or simply
      African is an appropriate and necessary prefix for an ethnic label, for example,
      African Caribbean or African Kenyan or African Surinamese (3) documents should
      define the ethnic labels (4) the label Black should be phased out except when
      used in political contexts.

PMID- 16286486
TI  - Terms in reproductive and perinatal epidemiology: 2. Perinatal terms.
AB  - This is the second of a two part glossary of terms used in reproductive and
      perinatal epidemiology. The purpose is to provide a reference for terms that are
      widely (if not always consistently) used in this field. While a glossary cannot
      resolve all these problems, it provides a point of reference for understanding
      them. Part 1 covered terms relevant mostly to events and conditions before birth.
      Part 2 emphasises terms used during the time around and after birth.

PMID- 16286488
TI  - The question is not: "is race or class more important?".

PMID- 16286487
TI  - A brief conceptual tutorial on multilevel analysis in social epidemiology:
      interpreting neighbourhood differences and the effect of neighbourhood
      characteristics on individual health.
AB  - STUDY OBJECTIVE: Using a conceptual rather than a mathematical approach, this
      article proposed a link between multilevel regression analysis (MLRA) and social
      epidemiological concepts. It has been previously explained that the concept of
      clustering of individual health status within neighbourhoods is useful for
      operationalising contextual phenomena in social epidemiology. It has been shown
      that MLRA permits investigating neighbourhood disparities in health without
      considering any particular neighbourhood characteristic but only information on
      the neighbourhood to which each person belongs. This article illustrates how to
      analyse cross level (neighbourhood-individual) interactions, how to investigate
      associations between neighbourhood characteristics and individual health, and how
      to use the concept of clustering when interpreting those associations and
      geographical differences in health. DESIGN AND PARTICIPANTS: A MLRA was performed
      using hypothetical data pertaining to systolic blood pressure (SBP) from 25 000
      subjects living in the 39 neighbourhoods of an imaginary city. Associations
      between individual characteristics (age, body mass index (BMI), use of
      antihypertensive drug, income) or neighbourhood characteristic (neighbourhood
      income) and SBP were analysed. RESULTS: About 8% of the individual differences in
      SBP were located at the neighbourhood level. SBP disparities and clustering of
      individual SBP within neighbourhoods increased along individual BMI.
      Neighbourhood low income was associated with increased SBP over and above the
      effect of individual characteristics, and explained 22% of the neighbourhood
      differences in SBP among people of normal BMI. This neighbourhood income effect
      was more intense in overweight people. CONCLUSIONS: Measures of variance are
      relevant to understanding geographical and individual disparities in health, and
      complement the information conveyed by measures of association between
      neighbourhood characteristics and health.

PMID- 16286489
TI  - Diseases of comfort: primary cause of death in the 22nd century.
AB  - CONTEXT: The world has started to feel the impact of a global chronic disease
      epidemic, which is putting pressure on our health care systems. If uncurbed, a
      new generation of "diseases of comfort" (such as those chronic diseases caused by
      obesity and physical inactivity) will become a major public health problem in
      this and the next century. OBJECTIVE: To describe the concept, causes, and
      prevention and control strategies of diseases of comfort. METHODS: Brokered by a
      senior research scientist specialised in knowledge translation, a chair, a
      president, and a past president of national public health associations
      contributed their views on the subject. RESULTS: Diseases of comfort have emerged
      as a price of living in a modern society. It is inevitable that these diseases
      will become more common and more disabling if human "progress" and civilisation
      continue toward better (more comfortable) living, without necessarily considering
      their effects on health. Modern technology must be combined with education,
      legislation, intersectoral action, and community involvement to create built and
      social environments that encourage, and make easy, walking, physical activity,
      and nutritious food choices, to reduce the health damaging effects of modern
      society for all citizens and not only the few. CONCLUSIONS: Public health needs
      to be more passionate about the health issues caused by human progress and adopt
      a health promotion stance, challenging the assumptions behind the notion of
      social "progress" that is giving rise to the burden of chronic disease and
      developing the skills to create more health promoting societies in which
      individual health thrives.

PMID- 16286490
TI  - Large scale food retailing as an intervention for diet and health: quasi
      experimental evaluation of a natural experiment.
AB  - OBJECTIVES: To assess the effect on fruit and vegetable consumption, self
      reported, and psychological health of a "natural experiment"-the introduction of
      large scale food retailing in a deprived Scottish community. DESIGN: Prospective
      quasi-experimental design comparing baseline and follow up data in an
      "intervention" community with a matched "comparison" community in Glasgow, UK.
      PARTICIPANTS: 412 men and women aged 16 or over for whom follow up data on fruit
      and vegetable consumption and GHQ-12 were available. MAIN OUTCOME MEASURES: Fruit
      and vegetable consumption in portions per day, poor self reported health, and
      poor psychological health (GHQ-12). MAIN RESULTS: Adjusting for age, sex,
      educational attainment, and employment status there was no population impact on
      daily fruit and vegetable consumption, self reported, and psychological health.
      There was some evidence for a net reduction in the prevalence of poor
      psychological health for residents who directly engaged with the intervention.
      CONCLUSIONS: Government policy has advocated using large scale food retailing as
      a social intervention to improve diet and health in poor communities. In contrast
      with a previous uncontrolled study this study did not find evidence for a net
      intervention effect on fruit and vegetable consumption, although there was
      evidence for an improvement in psychological health for those who directly
      engaged with the intervention. Although definitive conclusions about the effect
      of large scale retailing on diet and health in deprived communities cannot be
      drawn from non-randomised controlled study designs, evaluations of the impacts of
      natural experiments may offer the best opportunity to generate evidence about the
      health impacts of retail interventions in poor communities.

PMID- 16286491
TI  - Population impact of stricter adherence to recommendations for pharmacological
      and lifestyle interventions over one year in patients with coronary heart
      disease.
AB  - STUDY OBJECTIVE: To assess the potential number of lives saved associated with
      the full implementation of aspects of the National Service Framework (NSF) for
      coronary heart disease (CHD) in England using recently developed population
      impact measures. DESIGN: Modelling study. SETTING: Primary care. DATA SOURCES:
      Published data on prevalence of acute myocardial infarction and heart failure,
      baseline risk of mortality, the relative risk reduction associated with different
      interventions and the proportion treated, eligible for treatment and adhering to
      each intervention. MAIN RESULTS: Adopting the NSF recommendations for
      pharmacological interventions would prevent an extra 1027 (95% CI 418 to 1994)
      deaths in post-acute myocardial infarction (AMI) patients and an extra 37 899
      (95% CI 25 690 to 52 503) deaths in heart failure patients in the first year
      after diagnosis. Lifestyle based interventions would prevent an extra 848 (95% CI
      71 to 1 614) deaths in post-AMI patients and an extra 7249 (95% CI 995 to 16 696)
      deaths in heart failure patients. CONCLUSIONS: Moving from current to "best"
      practice as recommended in the NSF will have a much greater impact on one year
      mortality rates among heart failure patients compared with post-AMI patients.
      Meeting pharmacological based recommendations for heart failure patients will
      prevent more deaths than meeting lifestyle based recommendations. Population
      impact numbers can help communicate the impact on a population of the
      implementation of guidelines and, when created using local data, could help
      policy makers assess the local impact of implementing a range of health care
      targets.

PMID- 16286493
TI  - The burden of food related ill health in the UK.
AB  - STUDY OBJECTIVE: To quantify the burden of ill health in the UK that can be
      attributed to food (the burden of food related ill health). DESIGN: Review and
      further analysis of the results of work concerned with estimates of the burden of
      disease measured as morbidity, mortality, and in financial terms and with the
      proportion of that burden that can be attributed to food. MAIN RESULTS: Food
      related ill health is responsible for about 10% of morbidity and mortality in the
      UK and costs the NHS about 6 billion pounds annually. CONCLUSIONS: The burden of
      food related ill health measured in terms of mortality and morbidity is similar
      to that attributable to smoking. The cost to the NHS is twice the amount
      attributable to car, train, and other accidents, and more than twice that
      attributable to smoking. The vast majority of the burden is attributable to
      unhealthy diets rather than to food borne diseases.

PMID- 16286492
TI  - Trends in the sex ratio of California births, 1960-1996.
AB  - STUDY OBJECTIVE: The male sex ratio at birth (or the proportion of male births in
      a population) has been suggested as a sentinel environmental health indicator.
      Usually around 51%, the proportion may be dramatically decreased in offspring of
      persons with chemical exposures. Recent publications from the USA and elsewhere
      have noted a small but apparently declining male birth proportion, suggesting the
      effect of some environmental exposures. This paper sought to examine these trends
      more closely in California's large and diverse population. DESIGN: Using
      computerised birth certificate data, time trends were examined by multivariate
      linear and spline regression, controlling for demographic factors. SETTING:
      California. PARTICIPANTS: About 15 million births from 1960 to 1996. MAIN
      RESULTS: In the raw data, the male birth proportion is indeed declining. However,
      during this period, there were also shifts in demographics that influence the sex
      ratio. Controlling for birth order, parents' age, and race/ethnicity, different
      trends emerged. White births (which account for over 80%) continued to show a
      statistically significant decline, while other racial groups showed non
      statistically significant declines (Japanese, Native American, other), little or
      no change (black), or an increase (Chinese). Finally, when the white births were
      divided into Hispanic and non-Hispanic (possible since 1982), it was found that
      both white subgroups suggest an increase in male births. CONCLUSION: This
      analysis shows that the decline in male births in California is largely
      attributable to changes in demographics.

PMID- 16286494
TI  - Contextual effect on mortality of neighbourhood level education explained by
      earlier life deprivation.

PMID- 16286495
TI  - Maternal mental health and child nutritional status in four developing countries.
AB  - OBJECTIVE: To test the hypothesis that maternal common mental disorders (CMD) are
      associated with poorer child nutritional status in four developing countries
      (Ethiopia, India, Vietnam, and Peru). DESIGN: Community based cross sectional
      survey in 20 sites in each of the four countries. Maternal CMD measured by the
      self reporting questionnaire 20 items (SRQ20). Potential confounding factors
      include: household poverty, household composition, maternal characteristics such
      as age and education, child characteristics such as birth weight, age, and sex.
      Possible mediating factors included the child's physical health and breast
      feeding status. SETTING: Urban and rural, poor and middle income areas in each
      country. PARTICIPANTS: 2000 mothers and their children aged 6-18 months in each
      country. MAIN OUTCOME MEASURES: Child stunting and underweight measured using
      standard anthropometric techniques. RESULTS: Levels of maternal CMD and child
      malnutrition are high in each study setting. After adjusting for confounding
      factors, the odds ratios (OR) for the association of maternal CMD with child
      stunting are: India 1.4 (95%CI 1.2 to 1.6), Peru 1.1 (0.9 to 1.4), Vietnam 1.3
      (0.9 to 1.7), and Ethiopia 0.9 (0.7 to 1.2). For child underweight, the
      confounder adjusted ORs are: India 1.1 (0.9 to 1.4), Peru 0.9 (0.6 to 1.2),
      Vietnam 1.4 (1.1 to 1.8), and Ethiopia 1.1 (0.9 to 1.4). No clear evidence for
      effect modification by the child's age or sex was found. Possible mediating
      factors for the effect of maternal CMD on child malnutrition did not provide
      strong suggestions for potential mechanisms. CONCLUSIONS: There was a relation
      between high maternal CMD and poor child nutritional status in India and Vietnam.
      However, the findings from Peru and Ethiopia do not provide clear evidence for a
      similar association being present in non-Asian countries. Regardless of the
      direction of the relation, child nutrition programmes in Asia should consider
      incorporating promotion of maternal mental health.

PMID- 16286496
TI  - Youth smoking risk and community patterns of alcohol availability and control: a
      national multilevel study.
AB  - STUDY OBJECTIVE: To test whether college youth smoking risks are independently
      associated with community patterns of alcohol availability and control. DESIGN:
      Hierarchical multilevel multivariable modelling of cross sectional survey data.
      Outcomes included self reported current (past 30 day) cigarette smoking and heavy
      episodic (binge) drinking. SETTING: 120 nationally representative US colleges.
      PARTICIPANTS: 10 924 randomly selected students. MAIN RESULTS: Individual risks
      for smoking and binge drinking are independently associated with community
      patterns of alcohol availability, policy enforcement and control over and above
      individual perceptions about these factors, student and college characteristics,
      and school binge drinking rates. Youth exposed to high levels of alcohol
      availability are at higher risk of smoking (OR 3.61, 95% CI 1.75, 7.44) and binge
      drinking (OR 4.22, 95% CI 2.25, 7.93) than youth not so exposed; youth exposed to
      strongly enforced alcohol policy environments are at lower risk for smoking (OR
      0.30, 95% CI 0.16, 0.57) and binge drinking (OR 0.17, 95% CI 0.10, 0.31) than
      youth not so exposed; youth exposed to communities with strong parental controls
      are at lower risk for smoking (OR 0.05, 95% CI 0.01, 0.23) and binge drinking (OR
      0.06, 95% CI 0.01, 0.21) than youth not so exposed. Individual risks related to
      environmental exposures differ for youth with varying perceptions about alcohol
      availability and policy control. CONCLUSIONS: Drinking environments in US college
      communities comprise strong independent risks for smoking. Smoking prevention
      models should be tested that include environmental drinking prevention strategies
      tailored to underlying perceptions and experiences of college youth.

PMID- 16286497
TI  - Multilevel analysis of associations between socioeconomic status and injury among
      Canadian adolescents.
AB  - STUDY OBJECTIVE: To determine the contribution of individual and area level
      measures of socioeconomic status (SES) to the occurrence of various injury types
      among Canadian adolescents. DESIGN AND SETTING: Cross sectional Canadian data
      were used from two sources: (1) the 2001/02 health behaviour in school aged
      children survey (individual level SES measures, injury measures), and (2) the
      2001 Canada census of population (area level SES measures). Injury outcomes
      included: medically treated injury, injury hospitalisation, sport/recreational
      injury, and fighting injury. Multilevel logistic regression models were used to
      examine individual and area level SES measures as potential determinants of
      adolescent injury. PARTICIPANTS: 7235 students in grades 6-10 from 170 schools
      across Canada. MAIN RESULTS: Associations between SES and injury were identified
      for each injury outcome examined, although a clear direction of association was
      not present for the overall measure of medically treated injury. In general,
      lower SES was associated with increased risk for hospitalised and fighting
      injury. Higher SES was associated with increased risks for sport/recreational
      injury. Independent contributions of individual and area level measures of SES
      were seen for hospitalised and fighting injury. CONCLUSIONS: Associations between
      SES and adolescent injury exist; however, the direction of these relations
      becomes more apparent with particular indicators of SES and when homogenous
      injury outcomes are evaluated.

PMID- 16286498
TI  - Dose and duration of hormone use: understanding the effects of combined
      menopausal hormones on breast cancer better, 1976-2004.

PMID- 16286499
TI  - Income as mediator of the effect of occupation on the risk of myocardial
      infarction: does the income measurement matter?
AB  - AIM: To investigate whether the effect of occupational grade on the risk of
      myocardial infarction (MI) is mediated by income with different aspects of income
      taken into account. METHODS: Data were used from three prospective population
      studies conducted in Copenhagen. A total of 16 665 employees, 43% women, aged 20
      75 years, with an initial examination between 1974 and 1992 were followed up
      until 1999 for incident (hospital admission or fatal) MI. Register based
      information on job categories and income was used. RESULTS: During follow up, 855
      subjects were diagnosed with a MI: 708 men and 147 women (in total 47% fatal).
      The hazards by household and individual income showed a graded effect with a
      hazard ratio (HR) of 1.43 (95% CI 1.12 to 1.83) for the lowest household income
      group compared with the highest, whereas equivalent income showed an inverse "J
      shape" effect with a HR of 1.55 (95% CI 1.25 to 1.82) for the third income group
      compared with the highest. HR for unskilled workers as compared with executive
      managers was reduced from 1.55 (95% CI 1.24 to 1.93) to 1.42 (95% CI 1.12 to
      1.81) after adjustment for household income. CONCLUSIONS: Occupation and income
      are not mutually exclusive, but at least partly explained by or mediated through
      the other on the risk of MI. The mediating effect of income is independent of the
      choice of an income indicator. Income is not a big contributor to inequality in
      MI; probably because of the rather even income distribution in Denmark.

PMID- 16286502
TI  - A monetary incentive increases postal survey response rates for pharmacists.
AB  - BACKGROUND: Achieving acceptable response rates from health care providers via
      postal questionnaires is an ongoing challenge. The use of monetary incentives is
      one of the most effective strategies for increasing response rates. However, the
      effect and cost of such an incentive on retail pharmacists' response rates has
      not been well studied. METHODS: A sample of 700 pharmacies was selected at random
      from the electronic Yellow Pages in NSW Australia and mailed a brief survey
      regarding pharmacotherapies and advice for smoking cessation. Half of the sample
      was randomly allocated to receive an offer of an 14 US dollars gift voucher.
      RESULTS: The response rates were 65.9% for the voucher group and 53.5% for the no
      voucher group. The odds of response from the voucher group was 1.68 (95%CI =
      1.23, 2.30) times greater than for the no-voucher group. The cost per additional
      respondent was 67.95 US dollars. The incentive also reduced follow up costs by
      10%. CONCLUSIONS: A moderately sized monetary incentive is able to achieve a
      significant increase in response rates for retail pharmacists, thereby reducing
      potential bias in the sample.

PMID- 16286500
TI  - What makes an ad a cigarette ad? Commercial tobacco imagery in the lesbian, gay,
      and bisexual press.
AB  - OBJECTIVES: To determine the extent of commercial tobacco imagery in the lesbian,
      gay, and bisexual (LGB) press. METHODS: Content analysis of all advertising
      containing tobacco related text or imagery in 20 LGB community periodicals,
      published between January 1990 and December 2000. RESULTS: 3428 ads were found:
      689 tobacco product ads, 1607 ads for cessation products or services, 99 ads with
      a political message about tobacco, and 1033 non-tobacco ads that showed tobacco
      (NAST). Although cessation ads were numerically dominant, tobacco product ads and
      NAST occupied more space and were more likely to use images. NAST almost never
      had an anti-tobacco message. Formal sponsorship between tobacco and other
      companies was very rare. Lesbian periodicals had proportionally more NAST and
      fewer cessation ads. CONCLUSIONS: Cigarette ads were outnumbered by NAST.
      Although these ads do not usually show brands, and are unlikely to be the result
      of formal sponsorship agreements, they may be "selling" smoking. Tobacco control
      advocates should persuade editors to refuse tobacco product ads and those with
      gratuitous tobacco imagery.

PMID- 16286501
TI  - Linking environmental effects to health impacts: a computer modelling approach
      for air pollution.
AB  - STUDY OBJECTIVE AND SETTING: To develop a computer model, using a geographical
      information system (GIS), to quantify potential health effects of air pollution
      from a new energy from waste facility on the surrounding urban population.
      DESIGN: Health impacts were included where evidence of causality is sufficiently
      convincing. The evidence for no threshold means that annual average increases in
      concentration can be used to model changes in outcome. The study combined the
      "contours" of additional pollutant concentrations for the new source generated by
      a dispersion model with a population database within a GIS, which is set up to
      calculate the product of the concentration increase with numbers of people
      exposed within each enumeration district exposure response coefficients, and the
      background rates of mortality and hospital admissions for several causes. MAIN
      RESULTS: The magnitude of health effects might result from the increased PM10
      exposure is small-about 0.03 deaths each year in a population of 3 500 000, with
      0.04 extra hospital admissions for respiratory disease. Long term exposure might
      bring forward 1.8-7.8 deaths in 30 years. CONCLUSIONS: This computer model is a
      feasible approach to estimating impacts on human health from environmental
      effects but sensitivity analyses are recommended. RELEVANCE TO CLINICAL OR
      PROFESSIONAL PRACTICE: The availability of GIS and dispersion models on personal
      computers enables quantification of health effects resulting from the additional
      air pollution new industrial development might cause. This approach could also be
      used in environmental impact assessment. Care must be taken in presenting results
      to emphasise methodological limitations and uncertainties in the numbers.

PMID- 16286503
TI  - Radiation quality of photons in small and large receptors--a microdosimetric
      analysis.
AB  - The quality of different photon radiations in small and large receptors is
      assessed in terms of microdosimetry. Monte Carlo simulations are performed for
      the electrons released by photons. To represent the case of a small receptor,
      only electrons released by the non-degraded incident photons are tracked. For a
      large receptor, all electrons released in the complete degradation process are
      followed. Dose averaged values, y(D), of the lineal energy are derived from the
      simulated tracks for monoenergetic photons from 10 keV to 2 MeV. In
      microdosimetry, the dose mean lineal energy is the major parameter of radiation
      quality. The results demonstrate distinct differences in radiation quality
      between high-energy gamma rays and conventional X rays that are present not just
      in small cell samples but also in large receptors, such as the human body. The
      values of y(D) suggest that, for both small and large receptors, conventional X
      rays should be about twice as effective as gamma rays from 60Co.

PMID- 16286505
TI  - Death by association: BH3 domain-only proteins and liver injury.
AB  - Apoptosis, a prominent form of cell death, is a prime feature of many acute and
      chronic liver diseases. Apoptosis requires mitochondrial dysfunction, which is
      regulated by proteins of the Bcl-2 family. Whether or not a cell should live or
      die is controlled by the interaction of multidomain Bcl-2 proteins with
      proapoptotic BH3 domain-only proteins of this family. Current models suggest
      multidomain, antiapoptotic Bcl-2 proteins prevent mitochondrial dysfunction by
      sequestering and/or preventing activation of its proapoptotic relatives. BH3-only
      proteins initiate cell death by neutralizing and or ligating multidomain
      prosurvival Bcl-2 proteins. Thus BH3 domain-only proteins are paramount in the
      apoptotic process as exemplified by the role of the BH3 domain-only protein Bid
      in liver injury. In this concise review, we will focus on how these BH3 domain
      only proteins are regulated in the cell, their association with the Bcl-2 family
      of proteins, and finally, current information regarding their involvement in
      liver cell apoptosis and injury.

PMID- 16286504
TI  - Iron Imports. II. Iron uptake at the apical membrane in the intestine.
AB  - How does iron enter enterocytes? Ablating SLC11A2, the gene for the divalent
      metal ion transporter DMT1, supports evidence from the Belgrade rat and mk mouse
      models establishing DMT1 as the primary mechanism serving apical uptake of
      nonheme iron. DMT1 harnesses the energy from the proton electrochemical potential
      gradient to drive active transport of Fe(2+) (and perhaps Mn(2+) and other metal
      ions) into enterocytes. Fe(III) must first be reduced by ascorbic acid and
      surface ferrireductases. Among these is duodenal cytochrome B (DcytB), but lack
      of an obvious phenotype in DcytB (Cybrd1) knockout mice suggests ferrireductase
      redundancy. Our understanding of heme absorption has lagged, but the time is ripe
      for gains.

PMID- 16286506
TI  - Quantitative analysis of the voltage-dependent gating of mouse parotid ClC-2
      chloride channel.
AB  - Various ClC-type voltage-gated chloride channel isoforms display a double barrel
      topology, and their gating mechanisms are thought to be similar. However, we
      demonstrate in this work that the nearly ubiquitous ClC-2 shows significant
      differences in gating when compared with ClC-0 and ClC-1. To delineate the gating
      of ClC-2 in quantitative terms, we have determined the voltage (V(m)) and time
      dependence of the protopore (P(f)) and common (P(s)) gates that control the
      opening and closing of the double barrel. mClC-2 was cloned from mouse salivary
      glands, expressed in HEK 293 cells, and the resulting chloride currents (I(Cl))
      were measured using whole cell patch clamp. WT channels had I(Cl) that showed
      inward rectification and biexponential time course. Time constants of fast and
      slow components were approximately 10-fold different at negative V(m) and
      corresponded to P(f) and P(s), respectively. P(f) and P(s) were approximately 1
      at -200 mV, while at V(m) > or = 0 mV, P(f) approximately 0 and P(s)
      approximately 0.6. Hence, P(f) dominated open kinetics at moderately negative
      V(m), while at very negative V(m) both gates contributed to gating. At V(m) > or
      = 0 mV, mClC-2 closes by shutting off P(f). Three- and two-state models described
      the open-to-closed transitions of P(f) and P(s), respectively. To test these
      models, we mutated conserved residues that had been previously shown to eliminate
      or alter P(f) or P(s) in other ClC channels. Based on the time and V(m)
      dependence of the two gates in WT and mutant channels, we constructed a model to
      explain the gating of mClC-2. In this model the E213 residue contributes to P(f),
      the dominant regulator of gating, while the C258 residue alters the V(m)
      dependence of P(f), probably by interacting with residue E213. These data provide
      a new perspective on ClC-2 gating, suggesting that the protopore gate contributes
      to both fast and slow gating and that gating relies strongly on the E213 residue.

PMID- 16286507
TI  - Evolution of skeletal type e-c coupling: a novel means of controlling calcium
      delivery.
AB  - The functional separation between skeletal and cardiac muscles, which occurs at
      the threshold between vertebrates and invertebrates, involves the evolution of
      separate contractile and control proteins for the two types of striated muscles,
      as well as separate mechanisms of contractile activation. The functional link
      between electrical excitation of the surface membrane and activation of the
      contractile material (known as excitation-contraction [e-c] coupling) requires
      the interaction between a voltage sensor in the surface membrane, the
      dihydropyridine receptor (DHPR), and a calcium release channel in the
      sarcoplasmic reticulum, the ryanodine receptor (RyR). Skeletal and cardiac
      muscles have different isoforms of the two proteins and present two structurally
      and functionally distinct modes of interaction. We use structural clues to trace
      the evolution of the dichotomy from a single, generic type of e-c coupling to a
      diversified system involving a novel mechanism for skeletal muscle activation.
      Our results show that a significant structural transition marks the protochordate
      to the Craniate evolutionary step, with the appearance of skeletal muscle
      specific RyR and DHPR isoforms.

PMID- 16286509
TI  - Spore number control and breeding in Saccharomyces cerevisiae: a key role for a
      self-organizing system.
AB  - Spindle pole bodies (SPBs) provide a structural basis for genome inheritance and
      spore formation during meiosis in yeast. Upon carbon source limitation during
      sporulation, the number of haploid spores formed per cell is reduced. We show
      that precise spore number control (SNC) fulfills two functions. SNC maximizes the
      production of spores (1-4) that are formed by a single cell. This is regulated by
      the concentration of three structural meiotic SPB components, which is dependent
      on available amounts of carbon source. Using experiments and computer simulation,
      we show that the molecular mechanism relies on a self-organizing system, which is
      able to generate particular patterns (different numbers of spores) in dependency
      on one single stimulus (gradually increasing amounts of SPB constituents). We
      also show that SNC enhances intratetrad mating, whereby maximal amounts of
      germinated spores are able to return to a diploid lifestyle without intermediary
      mitotic division. This is beneficial for the immediate fitness of the population
      of postmeiotic cells.

PMID- 16286511
TI  - A common beta2-adrenoceptor gene haplotype protects against obesity in Swedish
      women.
AB  - The beta2-adrenoceptor gene may be of particular importance for human obesity
      because catecholamines have a central role in energy expenditure both as
      neurotransmitters and hormones. The gene is highly polymorphic, and individual
      polymorphisms have previously been examined for their relationship to obesity,
      but results are conflicting. We performed a haplotype analysis of the beta2
      adrenoceptor gene in 1354 women and 421 men, all healthy and at least second
      generation Scandinavian and with a large interindividual variation in body fat
      mass. We found three common haplotypes. One of these haplotypes, identified as T,
      A, C, C at nucleotide positions -47, 46, 79, and 491, was in its homozygote form
      more common among lean (18%) than obese (13%) women (p = 0.0028), but there was
      no association with obesity in men (p = 0.47). Women who were homozygous for this
      haplotype had lower BMI (p = 0.009) and percentage body fat (p = 0.005) in
      comparison with those having other haplotypes or being heterozygous for TACC. The
      data suggest an important role of the beta2-adrenoceptor gene in obesity because
      a common haplotype has recessive protective effects against excess body fat, at
      least in women.

PMID- 16286508
TI  - p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective
      effect on huntingtin-induced cell death.
AB  - Autophagic degradation of ubiquitinated protein aggregates is important for cell
      survival, but it is not known how the autophagic machinery recognizes such
      aggregates. In this study, we report that polymerization of the polyubiquitin
      binding protein p62/SQSTM1 yields protein bodies that either reside free in the
      cytosol and nucleus or occur within autophagosomes and lysosomal structures.
      Inhibition of autophagy led to an increase in the size and number of p62 bodies
      and p62 protein levels. The autophagic marker light chain 3 (LC3) colocalized
      with p62 bodies and co-immunoprecipitated with p62, suggesting that these two
      proteins participate in the same complexes. The depletion of p62 inhibited
      recruitment of LC3 to autophagosomes under starvation conditions. Strikingly, p62
      and LC3 formed a shell surrounding aggregates of mutant huntingtin. Reduction of
      p62 protein levels or interference with p62 function significantly increased cell
      death that was induced by the expression of mutant huntingtin. We suggest that
      p62 may, via LC3, be involved in linking polyubiquitinated protein aggregates to
      the autophagy machinery.

PMID- 16286512
TI  - Low- and high-carbohydrate diets: body composition differences in rats.
AB  - OBJECTIVE: To determine differences in adipose tissue mass, cell size, and lipid
      metabolism transcripts and differences in composition of body weight loss and
      energy expenditure (EE) after isoenergetic, energy-restricted intake of low
      carbohydrate/high-fat/high-protein (LC) and high-carbohydrate/low-fat/moderate
      protein (HC) diets. RESEARCH METHODS AND PROCEDURES: Ten-week old female Sprague
      Dawley rats were fed a high-fat diet ad libitum for 8 weeks to induce weight gain
      and fat deposition. Weight-matched rats were then assigned to isoenergetic LC
      (Atkins) and HC (American Dietary Association Exchange) diets for 10 weeks at 65%
      of ad libitum energy intake. RESULTS: There was no significant difference in the
      serum lipid profiles or amount of body weight lost between the HC and LC groups,
      whereas a higher insulin sensitivity index (p < 0.01) resulted from the HC
      compared with the LC diet. Compared with the post-restriction LC group, the HC
      group demonstrated (p < 0.05) higher EE during active hours, lower mRNA levels
      for the lipogenic genes peroxisome proliferator-activated receptor gamma2,
      lipoprotein lipase, and, adipocyte fatty acid binding protein, decreased
      adipocyte cell volume, and decreased fat mass. DISCUSSION: Results indicated down
      regulation of lipogenic genes, decreased fat mass, and, therefore, improved body
      composition in the post-restriction HC compared with the LC group. The small mean
      differences between the two diet groups (p = 0.11) in 24-hour EE over the 10
      weeks of diet intervention would account for the majority of the lower mean body
      weights in the post-restriction HC group. These data suggest that macronutrient
      composition of the diet influences body composition and indicate a distinction
      between HC and LC diets.

PMID- 16286510
TI  - Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on
      mitogenic responses of cancer cells.
AB  - The cell surface heparan sulfate proteoglycan (HSPG) glypican-1 is up-regulated
      by pancreatic and breast cancer cells, and its removal renders such cells
      insensitive to many growth factors. We sought to explain why the cell surface
      HSPG syndecan-1, which is also up-regulated by these cells and is a known growth
      factor coreceptor, does not compensate for glypican-1 loss. We show that the
      initial responses of these cells to the growth factor FGF2 are not glypican
      dependent, but they become so over time as FGF2 induces shedding of syndecan-1.
      Manipulations that retain syndecan-1 on the cell surface make long-term FGF2
      responses glypican independent, whereas those that trigger syndecan-1 shedding
      make initial FGF2 responses glypican dependent. We further show that syndecan-1
      shedding is mediated by matrix metalloproteinase-7 (MMP7), which, being anchored
      to cells by HSPGs, also causes its own release in a complex with syndecan-1
      ectodomains. These results support a specific role for shed syndecan-1 or MMP7
      syndecan-1 complexes in tumor progression and add to accumulating evidence that
      syndecans and glypicans have nonequivalent functions in vivo.

PMID- 16286513
TI  - Hyperphagia and obesity in Na,K-ATPase alpha2 subunit-defective mice.
AB  - OBJECTIVE: The Na,K-ATPase alpha2 subunit gene (Atp1a2) is expressed in the
      brain, skeletal muscles, heart, and adipocytes. Specific function of the alpha2
      subunit, such as involvement in differentiation and function of adipocytes, has
      not been addressed. The aim of this study was to examine whether Atp1a2-defective
      heterozygous mice show obesity and reveal the mechanisms underlying the obesity.
      RESEARCH METHODS AND PROCEDURES: We measured the differentiation and glucose
      uptake function of in vitro-differentiated adipocytes derived from embryonic
      fibroblasts of Atp1a2-defective mice. Food intake, body temperature, metabolic
      rate, and spontaneous activity and mRNA levels of neuropeptide genes were
      compared between the heterozygous and wild-type adult mice. RESULTS: Atp1a2
      heterozygous female mice developed obesity after middle age. The time course of
      in vitro adipocyte differentiation of embryonic fibroblasts isolated from wild
      type, heterozygous, and homozygous mice was not different, glucose and Rb uptake
      activities of the in vitro-differentiated adipocytes were not altered, and the
      effects of insulin on glucose uptake and those of monensin and ouabain on Rb
      uptake were similar among the genotypes. However, food intake in the light phase
      was significantly greater in the heterozygous mice than the wild type in the 24
      hour dark-light cycle, whereas it was similar under constant-light condition.
      Body temperature, metabolic rate at rest, and spontaneous motor activity of the
      heterozygous mice were similar to those of the wild type. Orexin mRNA level was
      lower in heterozygous than wild-type mice. DISCUSSION: The Na,K-ATPase alpha2
      subunit is not involved in the differentiation or in glucose and Rb uptake
      function of in vitro-differentiated adipocytes. Hyperphagia is the likely primary
      cause of obesity in Atp1a2 heterozygous mice.

PMID- 16286514
TI  - Altered hypothalamic signaling and responses to food deprivation in rats fed a
      low-carbohydrate diet.
AB  - OBJECTIVE: To model how consuming a low-carbohydrate (LC) diet influences food
      intake and body weight. RESEARCH METHODS AND PROCEDURES: Food intake and body
      weight were monitored in rats with access to chow (CH), LC-high-fat (HF), or HF
      diets. After 8 weeks, rats received intracerebroventricular injections of a
      melanocortin agonist (melanotan-II) and antagonist (SHU9119), and feeding
      responses were measured. At sacrifice, plasma hormones and hypothalamic
      expression of mRNA for proopiomelanocortin (POMC), melanocortin-4 receptor,
      neuropeptide Y (NPY), and agouti related protein (AgRP) were assessed. A second
      set of rats had access to diet (chow or LC-HF) for 4 weeks followed by 24 h food
      deprivation on two occasions, after which food intake and hypothalamic POMC, NPY,
      and AgRP mRNA expression were measured. RESULTS: HF rats consumed more food and
      gained more weight than rats on CH or LC-HF diets. Despite similar intakes and
      weight gains, LC-HF rats had increased adiposity relative to CH rats. LC-HF rats
      were more sensitive to melanotan-II and less sensitive to SHU9119. LC-HF rats had
      increased plasma leptin and ghrelin levels and decreased insulin levels, and
      patterns of NPY and POMC mRNA expression were consistent with those of food
      deprived rats. LC-HF rats did not show rebound hyperphagia after food
      deprivation, and levels NPY, POMC, and AgRP mRNA expression were not affected by
      deprivation. DISCUSSION: Our results demonstrate that an LC diet influences
      multiple systems involved in the controls of food intake and body weight. These
      data also suggest that maintenance on an LC-HF diet affects food intake by
      reducing compensatory responses to food deprivation.

PMID- 16286515
TI  - The association between plasma adiponectin and insulin sensitivity in humans
      depends on obesity.
AB  - OBJECTIVE: In humans, low plasma adiponectin concentrations precede a decrease in
      insulin sensitivity and predict type 2 diabetes independently of obesity.
      However, it is possible that the contribution of adiponectin to insulin
      sensitivity is not equally strong over the whole range of obesity. RESEARCH
      METHODS AND PROCEDURES: We investigated the cross-sectional association between
      plasma adiponectin levels and insulin sensitivity in different ranges of body fat
      content [expressed as percentage of body fat (PFAT)] in a large cohort of normal
      glucose-tolerant subjects (n = 900). All individuals underwent an oral glucose
      tolerance test (OGTT), and 299 subjects additionally a euglycemic
      hyperinsulinemic clamp. In longitudinal analyses, the association of adiponectin
      at baseline with change in insulin sensitivity was investigated in a subgroup of
      108 subjects. RESULTS: In cross-sectional analyses, the association between
      plasma adiponectin and insulin sensitivity, adjusted for age, gender, and PFAT,
      depended on whether subjects were lean or obese [p for interaction adiponectin x
      PFAT = <0.001 (OGTT) and 0.002 (clamp)]. Stratified by quartiles of PFAT,
      adiponectin did not correlate significantly with insulin sensitivity in subjects
      in the lowest PFAT quartile (R2 = 0.10, p = 0.13, OGTT; and R2 = 0.10, p = 0.57,
      clamp), whereas the association in the upper PFAT quartile was rather strong (R2
      = 0.36, p < 0.0001, OGTT; and R2 = 0.48, p = 0.003, clamp). In longitudinal
      analyses, plasma adiponectin at baseline preceded change in insulin sensitivity
      in obese (n = 54, p = 0.03) but not in lean (n = 54, p = 0.68) individuals.
      DISCUSSION: These data suggest that adiponectin is especially critical in
      sustaining insulin sensitivity in obese subjects. Thus, interventions to reduce
      insulin resistance by increasing adiponectin concentrations may be effective
      particularly in obese, insulin-resistant individuals.

PMID- 16286516
TI  - Low 25-hydroxyvitamin D does not affect insulin sensitivity in obesity after
      bariatric surgery.
AB  - OBJECTIVE: A positive correlation between levels of 25-hydroxyvitamin D [25(OH)D]
      and insulin sensitivity has been shown in healthy subjects. We aimed to test the
      hypothesis that concentration of 25(OH)D influences insulin sensitivity in
      obesity before and after weight loss. RESEARCH METHODS AND PROCEDURES: We
      investigated the relation between serum 25(OH)D and insulin sensitivity
      (estimated by euglycemic-hyperinsulinemic clamp) in 116 obese women (BMI > or =
      40 kg/m2) evaluated before and 5 and 10 years after biliopancreatic diversion
      (BPD). Body composition was estimated by the isotope dilution method. RESULTS:
      Prevalence of hypovitaminosis D was 76% in the obese status and 91% and 89% at 5
      and 10 years after BPD, respectively, despite ergocalciferol supplementation.
      25(OH)D concentration decreased from 39.2 +/- 22.3 in obesity (p = 0.0001) to
      27.4 +/- 16.4 and 25.1 +/- 13.9 nM 5 and 10 years after BPD, respectively. Whole
      body glucose uptake increased from 24.27 +/- 4.44 at the baseline to 57.29 +/-
      11.56 and 57.71 +/- 8.41 mumol/kg(fat free mass) per minute 5 and 10 years after
      BPD, respectively (p = 0.0001). Predictor of 25(OH)D was fat mass (R2 = 0.26, p =
      0.0001 in obesity; R2 = 0.20, p = 0.02 after BPD). Parathormone correlated with
      fat mass (R2 = 0.19; p = 0.0001) and BMI (R2 = 0.053; p = 0.01) and inversely
      with M value (R2 = 0.16; p = 0.0001), but only in obese subjects. DISCUSSION: A
      high prevalence of hypovitaminosis D was observed in morbid obesity both before
      and after BPD. Low 25(OH)D did not necessarily imply increased insulin resistance
      after BPD, a condition where, probably, more powerful determinants of insulin
      sensitivity overcome the low circulating 25(OH)D levels. However, the present
      data cannot exclude some kind of influence of vitamin D status on glucose and
      insulin metabolism.

PMID- 16286517
TI  - Effect of orlistat in obese patients with binge eating disorder.
AB  - OBJECTIVE: Binge eating disorder represents a significant public health problem,
      with up to 50% of weight loss program participants displaying this disorder. In
      previous studies with orlistat, patients with binge eating disorder were
      excluded. The goal of this study was to assess the efficacy of orlistat in obese
      patients with binge eating disorder. RESEARCH METHODS AND PROCEDURES: Eighty-nine
      patients with clinically diagnosed binge eating disorder and a BMI > or = 30
      kg/m2 were randomized in double-blind fashion to 24 weeks of treatment with 120
      mg of orlistat or placebo three times daily, in combination with a mildly reduced
      calorie diet. RESULTS: After 24 weeks, the mean weight loss from baseline for
      orlistat-treated patients was significantly greater than for patients receiving
      placebo (-7.4% vs. -2.3%; p = 0.0001) (intent-to-treat analysis). The overall
      Eating Disorder Inventory 2 score at week 24 was significantly lower in patients
      treated with orlistat than in those in the placebo group (p = 0.011). DISCUSSION:
      Orlistat may be considered as part of the management for patients with obesity
      and binge eating disorder.

PMID- 16286518
TI  - Meta-analysis of the association of the Trp64Arg polymorphism in the beta3
      adrenergic receptor with insulin resistance.
AB  - OBJECTIVE: To clarify the possible association between the Trp64Arg polymorphism
      and insulin resistance (IR). RESEARCH METHODS AND PROCEDURES: Articles evaluating
      the effect of the Trp64Arg polymorphism on IR were identified on the MEDLINE and
      PubMed databases from 1995 to February, 2004. After extraction of relevant data,
      main and subgroup meta-analyses were performed to assess the differences in IR
      indices between Trp/Trp and Trp/Arg genotypes. RESULTS: Forty eligible papers
      containing 56 subgroups were included in this meta-analysis. Among a total of
      12,805 subjects, 21.9% had Trp64Arg mutation: 20.8%, heterozygotes and 1.1%,
      homozygotes. Significant associations were found between this mutation and some
      indices of IR. The weighted mean difference in fasting insulin, 120-minute
      insulin level after oral glucose tolerance test, and homeostasis model assessment
      between Arg64 and Trp64 was 0.23 [95% confidence interval (CI), 0.05 to 0.42] pM,
      0.89 (95% CI, 0.30 to 1.48) pM, and 0.55 (95% CI, 0.14 to 0.96), respectively.
      Subgroup analysis further indicated that this significant association existed
      only in the Asian population (p < 0.01) and in the obese (p = 0.02) and diabetes
      subgroups (p = 0.03). DISCUSSION: Numerous studies have been conducted to examine
      the relationship between the beta3-adrenergic receptor Trp64Arg polymorphism and
      components of IR syndrome. However, the results have been inconsistent and have
      led to controversy about whether this polymorphism is associated with these
      clinical features. The current meta-analysis demonstrated the moderate effects of
      the Trp64Arg polymorphism on IR in the Asian population and in obese and diabetic
      subgroups.

PMID- 16286519
TI  - The impact of calcium and dairy product consumption on weight loss.
AB  - OBJECTIVE: Recent evidence suggests that diets high in calcium and dairy products
      are associated with lower body weight, particularly lower body fat levels. The
      purpose of this study was to compare weight and body fat loss on a calorie
      restricted, low-dairy (CR) vs. high-dairy (CR+D) diet. RESEARCH METHODS AND
      PROCEDURES: Fifty-four subjects (BMI 30 +/- 2.5 kg/m2, 45 +/- 6.6 years, 4 men)
      were randomly assigned to calorie-restricted (-500 kcal/d) low-dairy calcium (n =
      29; approximately 1 serving dairy/d, 500 mg/d calcium) or high-dairy calcium (n =
      25; 3 to 4 servings dairy/d, 1200 to 1400 mg/d calcium) diets for 12 months. Main
      outcome measures included change in weight (kilograms) and body fat (percentage).
      RESULTS: There were no significant differences between groups at baseline. At 12
      months, weight and body fat loss were not significantly different. Subjects in
      the CR vs. CR+D conditions lost 9.6 +/- 6.5 vs. 10.8 +/- 5.9 kg (p = 0.56) and
      9.0 +/- 3.8 vs. 10.1 +/- 3.6 kg body fat (p = 0.37). DISCUSSION: These findings
      suggest that a high-dairy calcium diet does not substantially improve weight loss
      beyond what can be achieved in a behavioral intervention.

PMID- 16286520
TI  - Calcium and dairy intake and measures of obesity in hyper- and
      normocholesterolemic children.
AB  - OBJECTIVE: Calcium intake has been inversely associated with body weight and body
      fatness in adults and, to a lesser extent, in children. Dairy intake has been
      inversely associated with metabolic syndrome in overweight but not normal-weight
      adults. We assessed whether intakes of calcium and dairy foods were associated
      with measures of obesity in hypercholesterolemic (HC) and normocholesterolemic
      (non-HC) children at baseline and over 1 year. RESEARCH METHODS AND PROCEDURES:
      Non-obese 4- to 10-year-old HC and non-HC children (342) completed three 24-hour
      dietary recalls and provided measures of relative weight (BMI and BMI z scores)
      and adiposity (sum of skinfolds, trunk skinfolds) at baseline, 3, 6, and 12
      months. Cross-sectional and longitudinal regression analyses, stratified by
      cholesterol risk status (HC vs. non-HC) and age (4 to 6 years and 7 to 10 years)
      and adjusted for potential confounders, were conducted. RESULTS: After adjusting
      for age, sex, energy intake, and percentage energy from fat, calcium intake was
      inversely associated with BMI, sum of skinfolds, and trunk skinfolds at baseline
      and over 1 year in the 7- to 10-year-old non-HC children. Results from the
      regression models also indicated an inverse relation between intake of dairy
      foods and measures of obesity at baseline in these children. Calcium or dairy
      intake was not associated with measures of obesity in HC children or in the 4- to
      6-year-old non-HC children. DISCUSSION: These results suggest a complex relation
      among intake of calcium and dairy foods, measures of obesity, age, and serum
      cholesterol in children. Older children without risk of metabolic syndrome may
      benefit most from increased calcium intake.

PMID- 16286521
TI  - Results of go girls: a weight control program for overweight African-American
      adolescent females.
AB  - OBJECTIVE: Go Girls was a church-based nutrition and physical activity program
      designed for overweight African-American (AA) adolescent females. RESEARCH
      METHODS AND PROCEDURES: Ten predominantly middle-socioeconomic churches were
      randomized to either a high-intensity (20 to 26 sessions) or moderate-intensity
      (six sessions) culturally tailored behavioral group intervention delivered over 6
      months. Each session included an experiential behavioral activity, approximately
      30 minutes of physical activity, and preparation and tasting of healthy foods. In
      the high-intensity group, girls also received four to six telephone counseling
      calls. From the 10 churches, 123 girls completed baseline and 6-month post-test
      assessments. The primary outcome was BMI; secondary outcomes included waist and
      hip circumferences, percentage body fat estimated by bioimpedance, serum insulin,
      glucose, and lipids, and cardiovascular fitness at 6-month follow-up. Selected
      measures were also collected at 1-year follow-up. RESULTS: At 6-month follow-up,
      the net difference between the high- and moderate-intensity groups was 0.5 BMI
      units. This difference was not statistically significant (p = 0.20). There were
      no significant group differences in secondary outcomes. Girls in the high
      intensity condition, however, who attended more than three-quarters of the
      sessions had significantly lower BMI and percentage body fat relative to girls in
      the high-intensity group who attended fewer sessions. Findings at 1-year follow
      up mirrored those at 6 months. DISCUSSION: We concluded that the intervention was
      not effective in reducing adiposity, although there were some positive findings
      among high attenders. Despite the null result, the intervention was generally
      well received by participants. Future interventions may require greater dose and
      a more structured dietary change program.

PMID- 16286522
TI  - The influence of parenting change on pediatric weight control.
AB  - OBJECTIVE: Parenting style was examined as a predictor of weight loss maintenance
      in behavioral family-based pediatric obesity treatment. RESEARCH METHODS AND
      PROCEDURES: Fifty obese children who participated in a behavioral family-based
      pediatric obesity treatment were studied. Hierarchical regression tested the
      incremental effect of baseline parenting and parenting during treatment on
      children's percentage overweight change over 12 months, beyond demographics and
      adherence to targeted behaviors. RESULTS: Children's percentage overweight
      significantly decreased at 6 (-16.3) and 12 (-11.1) months. Adherence to program
      goals significantly increased variance accounted for in the regression model by
      10.8%, whereas adding baseline father acceptance and change in father acceptance
      accounted for another 20.5%. The overall model accounted for 40.6% of the
      variance in pediatric weight control. ANOVA showed significantly greater
      percentage overweight decrease from baseline for youth with fathers who increased
      their acceptance vs. those who decreased acceptance at 6 (-19.8 vs. -14.6) and 12
      (-17.4 vs. -8.1) months. DISCUSSION: Youth who perceive an increase in father
      acceptance after treatment had better changes in percentage overweight over 12
      months than youth with lower ratings of father acceptance. Future directions
      include examining how other parenting dimensions impact pediatric obesity
      treatment outcome and how parental acceptance can be enhanced to improve child
      weight control.

PMID- 16286523
TI  - Obesity and cardiovascular disease risk factors in firefighters: a prospective
      cohort study.
AB  - OBJECTIVE: Obesity, despite being a significant determinant of fitness for duty,
      is reaching epidemic levels in the workplace. Firefighters' fitness is important
      to their health and to public safety. RESEARCH METHODS AND PROCEDURES: We
      examined the distribution of BMI and its association with major cardiovascular
      disease (CVD) risk factors in Massachusetts firefighters who underwent baseline
      (1996) and annual medical examinations through a statewide medical surveillance
      program over 5 years of follow-up. We also evaluated firefighters' weight change
      over time. RESULTS: The mean BMI among 332 firefighters increased from 29 at
      baseline to 30 at the follow-up examination (2001), and the prevalence of obesity
      increased from 35% to 40%, respectively (p < 0.0001). In addition, the proportion
      of firefighters with extreme obesity increased 4-fold at follow-up (from 0.6% to
      2.4%, p < 0.0001). Obese firefighters were more likely to have hypertension (p =
      0.03) and low high-density lipoprotein-cholesterol (p = 0.01) at follow-up.
      Firefighters with extreme obesity had an average of 2.1 CVD risk factors
      (excluding obesity) in contrast to 1.5 CVD risk factors for normal-weight
      firefighters (p = 0.02). Finally, on average, normal-weight firefighters gained
      1.1 pounds, whereas firefighters with BMI > or = 35 gained 1.9 pounds per year of
      active duty over 5 years of follow-up. DISCUSSION: Obesity is a major concern
      among firefighters and shows worsening trends over time. Periodic medical
      evaluations coupled with exercise and dietary guidelines are needed to address
      this problem, which threatens firefighters' health and may jeopardize public
      safety.

PMID- 16286524
TI  - Association of plasma resistin levels with coronary heart disease in women.
AB  - OBJECTIVE: To examine the association between plasma resistin levels and the
      presence of coronary heart disease (CHD) in women. RESEARCH METHODS AND
      PROCEDURES: Plasma resistin levels were measured in a case-control study
      including 185 women with angiographically confirmed CHD and 227 population-based
      female controls from the Coronary Risk Factors for Atherosclerosis in Women
      (CORA) study. RESULTS: After adjustment for age, smoking, family history of
      myocardial infarction, retirement, education, physical activity, menopausal
      status, hormone replacement use, BMI, hypertension, diabetes, and dyslipidemia,
      the odds ratio for CHD for women in the highest compared with lowest quintile of
      plasma resistin levels was 3.19 (95% confidence interval, 1.44 to 7.10; p log
      trend, 0.001). After additional adjustment for plasma C-reactive protein levels,
      this association was substantially attenuated and no longer significant (odds
      ratio, 1.80; 95% confidence interval, 0.69 ti 4.69; p trend = 0.23). DISCUSSION:
      These results suggest that plasma resistin levels are significantly associated
      with the presence of CHD in women; however, this association can largely be
      explained by concomitant inflammatory processes. Further studies are needed to
      determine the causal role of resistin in the development of CHD in humans.

PMID- 16286526
TI  - Weight change in adult life and health outcomes.
AB  - OBJECTIVE: To investigate the relationship between weight change in adult life
      and subsequent mortality and cancer incidence in women. RESEARCH METHODS AND
      PROCEDURES: In 1994 to 1995, all women (age range, 42 to 81) still under general
      practitioner observation in the United Kingdom's Royal College of General
      Practitioners Oral Contraception Study (n = 12,303) were sent a health survey
      asking about health and lifestyle issues, including current weight and weight at
      age 30. The main outcome measures were 6-year all-cause mortality and cancer
      incidence among different weight change deciles. Cox regression was used to
      calculate hazard ratios that were adjusted for: social class at recruitment, BMI
      at age 30, and age group, parity, smoking status, and hormone replacement therapy
      status in 1995. RESULTS: Women who had been obese at age 30 were more likely to
      die and significantly more likely to develop cancer in the 6 years after the
      health survey than non-obese respondents. Women reporting weight gains between
      age 30 and 1995 were significantly less likely to die during the 6 years after
      the health survey than those with a stable weight, whereas those with weight loss
      did not fare any better than those in the stable-weight group. DISCUSSION:
      Although obesity at young age was associated with subsequent mortality and cancer
      incidence, weight gain over a time period of 12 to 51 years appeared to be
      beneficial when compared with women with stable weight over the same time period.
      Further research is needed to confirm or refute our findings and to allow
      detailed examination of potential explanations for them.

PMID- 16286525
TI  - Mediating effects of inflammatory biomarkers on insulin resistance associated
      with obesity.
AB  - OBJECTIVE: Obesity is associated with elevated levels of biomarkers of
      inflammation and endothelial dysfunction [including C-reactive protein (CRP), E
      selectin, and intercellular adhesion molecule-1], as well as insulin resistance
      (IR) and type 2 diabetes. We tested the hypothesis that these biomarkers mediate
      associations among obesity, IR, and risk of diabetes. RESEARCH METHODS AND
      PROCEDURES: We stratified 510 initially non-diabetic women in the Nurses' Health
      Study cohort into four phenotypes above/below median BMI (27 kg/m2) and waist
      circumference (81 cm): low BMI-low waist (LBLW; N = 190), low BMI-high waist
      (LBHW; N = 74), high BMI-low waist (HBLW; N = 27), and high BMI-high waist (HBHW;
      N = 219). RESULTS: In models assessing associations of weight phenotype with IR
      [fasting insulin (FI)], adjusted for age and diabetes risk factors, mean FI was
      higher comparing HBHW women (13.6 microU/mL, p < 0.0001) and LBHW (11.5
      microU/mL, p = 0.02) with LBLW women (8.6 microU/mL); HBLW and LBLW women were
      not significantly different. Differences in FI levels were most strongly
      attenuated after adjustment for E-selectin comparing LBHW with LBLW women (11.7
      vs. 9.7 microU/mL, p = 0.2). DISCUSSION: In logistic regression models, LBHW
      predicted diabetes (risk factor-adjusted relative risk 2.06, 1.05 to 6.40),
      compared with LBLW, but was no longer significant after adjustment for E-selectin
      or CRP. After adjusting for CRP and E-selectin, only HBHW and E-selectin were
      significantly associated with risk of diabetes. In women with central adiposity
      and low BMI, endothelial dysfunction and inflammation may mediate the
      relationship among central fat, IR, and incident diabetes.

PMID- 16286527
TI  - Role of weight history on functional limitations and disability in late
      adulthood: the ARIC study.
AB  - OBJECTIVE: To examine associations of weight history with functional limitations
      and disability in white and African-American men and women. RESEARCH METHODS AND
      PROCEDURES: Data were from the Atherosclerosis Risk in Communities study (n =
      11,177). Associations of recalled weight status at age 25 and weight change from
      age 25 to ages 45 to 64 with functional limitations, activities of daily living
      (ADLs), and instrumental activities of daily living (IADLs) at follow-up (ages 52
      to 75) were examined using logistic regression. RESULTS: Obesity (BMI > or = 30
      kg/m2) at age 25 was associated with functional limitations and ADL and IADL
      impairment at follow-up in white and African-American men and women. For example,
      obese compared with normal weight (BMI, 18.5 to 24.9 kg/m(2)) white women had
      higher odds of mild [odds ratio (95% confidence interval), 1.97 (1.18 to 3.29)]
      and severe [9.81 (5.92 to 16.27)] functional limitations and ADL [3.48 (2.36 to
      5.13)] and IADL [2.95 (2.00 to 4.33)] impairment. In African-American women,
      obesity was associated with higher odds of mild [2.71 (1.14 to 6.41)] and severe
      [6.01 (2.53 to 14.26)] functional limitations and ADL [1.82 (1.10 to 3.00)] and
      IADL [2.39 (1.47 to 3.90)] impairment. Similar associations were found in men.
      Compared with weight maintenance (+/-10 lbs), large weight gain (>30 lbs) from
      age 25 to ages 45 to 64 was also associated with functional limitations and ADL
      and IADL impairment in white and African-American men and women. DISCUSSION:
      Maintenance of a healthy body weight throughout adulthood may play a role in
      preventing or delaying the onset of functional limitations and disability,
      resulting in increased quality of life and decreased health care costs.

PMID- 16286528
TI  - Eligibility for obesity treatment and risk of mortality in men.
AB  - OBJECTIVE: To evaluate the risk of all-cause and cardiovascular disease (CVD)
      mortality associated with each outcome of the NIH obesity treatment algorithm and
      to examine the effects of cardiorespiratory fitness on the risk of mortality
      associated with these outcomes. RESEARCH METHODS AND PROCEDURES: The NIH obesity
      treatment algorithm was applied to 18,666 men (20 to 64 years of age) from the
      Aerobics Center Longitudinal Study in Dallas, TX, examined between 1979 and 1995.
      Risk of all-cause and CVD mortality was assessed using Cox proportional hazards
      regression. RESULTS: A total of 7029 men (37.7%) met the criteria for needing
      weight loss treatment [overweight (BMI = 25 to 29.9 kg/m2 or WC > 102 cm) with >
      or =2 CVD risk factors or obese (BMI > or = 30 kg/m2)]. Mortality surveillance
      through 1996 identified 435 deaths (151 from CVD) during 191,364 man-years of
      follow-up. Compared with the normal weight reference group, the hazard ratios
      (95% confidence interval) for death from all causes were 0.63 (0.45 to 0.88),
      1.23 (0.98 to 1.54), 1.05 (0.60 to 1.85), and 1.71 (1.64 to 2.31) for men who
      were overweight with <2 CVD risk factors, overweight with > or = 2 CVD risk
      factors, obese with <2 CVD risk factors, and obese with > or =2 CVD risk factors,
      respectively. Corresponding hazard ratios for CVD mortality were 0.72 (0.38 to
      1.37), 1.67 (1.12 to 2.50), 1.69 (0.67 to 4.30), and 3.31 (2.07 to 5.30).
      Including physical fitness as a covariate significantly attenuated all risk
      estimates. DISCUSSION: The NIH obesity treatment algorithm is useful in
      identifying men at increased risk of premature mortality; however, including an
      assessment of fitness would help improve risk stratification among all groups of
      patients.

PMID- 16286529
TI  - High-sensitivity C-reactive protein in Japanese patients with type 2 diabetes.
AB  - OBJECTIVE: To assess the relationship between high-sensitivity (HS) C-reactive
      protein (CRP) and metabolic syndrome (MetS) or atherosclerosis and to assess
      effects of strict metabolic control on the degree of inflammation and MetS in
      patients with type 2 diabetes. RESEARCH METHODS AND PROCEDURES: Four hundred
      thirteen patients with diabetes were enrolled in the cross-sectional study. Of
      these 413 patients, 161 patients were further admitted for 2.4 +/- 0.4 weeks
      (mean +/- SD) to investigate the change in HS-CRP or other parameters under
      strict metabolic control. RESULTS: Log-transformed HS-CRP value (log HS-CRP) was
      strongly correlated with BMI (r = 0.448, p < 0.01). Log HS-CRP was also
      correlated with the presence of MetS or each component of MetS. Furthermore, a
      positive significant trend in HS-CRP levels was shown with an increasing number
      of MetS components (p < 0.05). Log HS-CRP showed a significant positive
      correlation with carotid artery intima-media thickness (IMT) (r = 0.152, p <
      0.01). In multiple step-wise regression analysis, BMI, hemoglobin A(1c), right
      IMT, duration of diabetes, and triglyceride were selected as explanatory
      variables for log HS-CRP (R2 = 0.412). Under strict metabolic control, HS-CRP was
      significantly (p < 0.01) lower, together with lower levels of other markers for
      MetS. The change in HS-CRP was significantly correlated with the change in BMI (r
      = 0.161, p = 0.04). DISCUSSION: In subjects with type 2 diabetes, HS-CRP levels
      are related to MetS and subclinical atherosclerosis. Strict weight management and
      metabolic control were associated with a reduction in HS-CRP levels, and changes
      in HS-CRP were related to changes in weight, supporting the hypothesis that
      lifestyle modification reduces inflammation and the risk of CHD.

PMID- 16286531
TI  - Longitudinal analyses among overweight, insulin resistance, and cardiovascular
      risk factors in children.
AB  - OBJECTIVE: It has been questioned whether insulin resistance or obesity is the
      central abnormality contributing to the cardiovascular risk factors dyslipidemia
      and hypertension in obesity. RESEARCH METHODS AND PROCEDURES: We studied weight
      status [SD score (SDS)-BMI], lipids (triglycerides, low-density lipoprotein- and
      high-density lipoprotein-cholesterol), blood pressure, and insulin resistance
      index [as homeostasis model assessment (HOMA) model] over a 1-year period in 229
      obese white children (median age 12 years). RESULTS: Any degree of decrease in
      HOMA was associated with significant decreases in triglycerides (p < 0.001),
      systolic blood pressure (p < 0.001), and diastolic blood pressure (p < 0.001),
      whereas the children with different changes in HOMA did not differ significantly
      in their weight changes. Only the children in the highest quartile of weight
      reduction (decrease in SDS-BMI > 0.5) demonstrated a significant decrease in
      systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), and
      triglycerides (p = 0.012), and an increase in high-density lipoprotein
      cholesterol (p = 0.023), whereas with a lower degree of weight loss, there were
      no significant changes in cardiovascular risk factors. In contrast with a lower
      degree of weight loss, a reduction of >0.5 SDS-BMI was associated with a
      significant decrease in HOMA (p < 0.001). DISCUSSION: Because blood pressure and
      triglycerides decreased with any degree of decrease in HOMA, independently of
      changes in weight status, these findings support the hypothesis that insulin
      resistance is the central abnormality contributing to these cardiovascular risk
      factors. Therefore, improving insulin resistance seems more important than
      reducing overweight to prevent or treat hypertension and dyslipidemia in obese
      children.

PMID- 16286530
TI  - Opposite contributions of trunk and leg fat mass with plasma lipase activities:
      the Hoorn study.
AB  - OBJECTIVE: Lipoprotein lipase (LPL) and hepatic lipase (HL) are essential in
      hydrolysis of triglyceride-rich lipoproteins. LPL activity is negatively, whereas
      HL activity is positively, associated with total body fat. We determined the
      associations of trunk and leg fat mass with plasma LPL and HL activities in a
      cross-sectional study. RESEARCH METHODS AND PROCEDURES: LPL and HL activities
      were determined in post-heparin plasma in a sample of 197 men and 209 women, 60
      to 87 years of age. A total body DXA scan was performed to determine trunk and
      leg fat mass. RESULTS: In women, but not in men, trunk fat mass was negatively
      associated with LPL activity, whereas leg fat mass was positively associated,
      after mutual adjustment and adjustment for age. Standardized betas (95%
      confidence interval) for trunk and leg fat mass were -0.24 (-0.41; -0.08) and
      0.14 (-0.02; 0.31), respectively (interaction by sex, p = 0.03). Larger trunk fat
      mass was associated with higher HL activity in men [0.48 (0.28; 0.68)] and women
      [0.40 (0.24; 0.56)]. A negative association of leg fat mass and HL activity was
      observed in men, although not statistically significant [-0.13 (-0.33; 0.06)],
      and in women [-0.28 (-0.38; -0.18)]. DISCUSSION: Abdominal fat is associated with
      unfavorable and femoral fat with favorable LPL and HL activities in plasma.

PMID- 16286532
TI  - Cost-effectiveness of a low-carbohydrate diet and a standard diet in severe
      obesity.
AB  - OBJECTIVE: Low-carbohydrate diets have become a popular alternative to standard
      diets for weight loss. Our aim was to compare the cost-effectiveness of these two
      diets. RESEARCH METHODS AND PROCEDURES: The patient population included 129
      severely obese subjects (BMI = 42.9) from a randomized trial; participants had a
      high prevalence of diabetes or metabolic syndrome. We compared within-trial
      costs, quality-adjusted life years (QALYs), and the incremental cost
      effectiveness ratio (CER) for the two study groups. We imputed missing values for
      QALYs. The CER was bootstrapped to derive 95% confidence intervals and to define
      acceptability cut-offs. We took a societal perspective for our analysis. RESULTS:
      Total costs during the one year of the trial were 6742 dollars +/- 6675 and 6249
      dollars +/- 5100 for the low-carbohydrate and standard groups, respectively (p =
      0.78). Participants experienced 0.64 +/- 0.02 and 0.61 +/- 0.02 QALYs during the
      one year of the study, respectively (p = 0.17 for difference). The point estimate
      of the incremental CER was -1225 dollars/QALY (i.e., the low-carbohydrate diet
      dominated the standard diet). However, in the bootstrap analysis, the wide spread
      of CERs caused the 95% confidence interval to be undefined. The probabilities
      that the low-carbohydrate diet was acceptable, using cut-offs of 50,000
      dollars/QALY, 100,000 dollars/QALY, and 150,000 dollars/QALY, were 72.4% 78.6%,
      and 79.8%, respectively. DISCUSSION: The low-carbohydrate diet was not more cost
      effective for weight loss than the standard diet in the patient population
      studied. Larger studies are needed to better assess the cost-effectiveness of
      dietary therapies for weight loss.

PMID- 16286533
TI  - Evaluation of Prader-Willi Syndrome gene MAGEL2 in severe childhood-onset
      obesity.
AB  - MAGEL2 is one of the five genes inactivated in Prader-Willi Syndrome, a
      neurodevelopmental chromosome microdeletion disorder modified by genomic
      imprinting. By early childhood, individuals with Prader-Willi Syndrome exhibit
      hypothalamic dysfunction, including hyperphagia, and become obese in the absence
      of behavioral intervention. Murine Magel2 is highly expressed in the hypothalamus
      during development. We screened the MAGEL2 open reading frame for mutations in
      genomic DNA samples from hyperphagic but non-dysmorphic individuals with severe
      childhood-onset obesity. Although no mutations likely to affect gene function
      were identified, we identified three variant alleles. We conclude that severe
      childhood-onset obesity is not commonly caused by MAGEL2 mutations.

PMID- 16286534
TI  - The 2.3 genotype of ESRRA23 of the ERR alpha gene is associated with a higher BMI
      than the 2.2 genotype.
AB  - ERR alpha (NR3B1) is an orphan nuclear receptor believed to be involved in energy
      metabolism and obesity. A 23-base pair sequence in the 5'-flanking region of the
      ERR alpha gene, referred to as ESRRA23, is polymorphic in human chromosomes.
      Here, we investigated the influence of the ESRRA23 polymorphism on obesity in 703
      Japanese individuals by analyzing indices of obesity and related lifestyle
      factors. The frequency of genotypes was similar to that reported in whites. The
      2.3-genotype was associated with a significantly higher BMI than was the 2.2
      genotype. An increased number of ESRRA23 repeats may be a genetic factor in human
      obesity.

PMID- 16286535
TI  - E-selectin genotypes and risk of type 2 diabetes in women: genetic and
      environmental contributions to serum soluble E-selectin concentrations.

PMID- 16286536
TI  - Soluble vascular cell adhesion molecule 1 and N-terminal pro-B-type natriuretic
      peptide in predicting ischemic stroke in patients with cerebrovascular disease.
AB  - BACKGROUND: Patients with stroke or transient ischemic attack are at high risk of
      another stroke, and there is need for improved strategies to predict recurrent
      stroke. OBJECTIVE: To assess the prognostic value of levels of soluble vascular
      cell adhesion molecule 1 (sVCAM-1), N-terminal pro-B-type natriuretic peptide (NT
      proBNP), C-reactive protein, homocysteine, renin, and lipids and lipoprotein
      particle concentration and size in patients with previous stroke or transient
      ischemic attack. DESIGN, SETTING, AND PARTICIPANTS: A nested case-control study
      of participants of the Perindopril Protection Against Recurrent Stroke Study was
      performed. The Perindopril Protection Against Recurrent Stroke Study was a
      placebo-controlled trial of a perindopril erbumine-based, blood pressure-lowering
      regimen that reduced ischemic stroke risk by 24% among individuals with previous
      stroke or transient ischemic attack. Each of 252 patients who experienced
      ischemic stroke during a mean follow-up of 3.9 years was matched to 1 to 3
      control patients. Matching variables were age, sex, treatment allocated, region,
      and most recent qualifying event at randomization. MAIN OUTCOME MEASURES: Risk of
      ischemic stroke predicted by baseline levels of sVCAM-1, NT-proBNP, C-reactive
      protein, homocysteine, renin, and lipids and lipoprotein particle concentration
      and size. RESULTS: Levels of sVCAM-1 and NT-proBNP predicted recurrent ischemic
      stroke. The odds ratio for patients in the highest, as compared with the lowest,
      quarter was 2.24 (95% confidence interval, 1.35-3.73) for sVCAM-1 level and 1.62
      (95% confidence interval, 0.98-2.69) for NT-proBNP level, after adjustment for
      matching and other risk factors. Patients in the highest quarters for both sVCAM
      1 and NT-proBNP levels had 3.6 times the risk of recurrent ischemic stroke
      compared with patients in the lowest quarters for both biologic markers. Level of
      sVCAM-1 was similarly predictive of ischemic stroke in patients allocated to
      placebo and perindopril-based therapy. Baseline plasma levels of C-reactive
      protein, homocysteine, renin, and lipids and lipoprotein particle concentration
      and size did not predict recurrent ischemic stroke risk. CONCLUSION: Measurement
      of sVCAM-1 and NT-proBNP levels provides prognostic information for recurrent
      ischemic stroke beyond traditional risk factors.

PMID- 16286537
TI  - Multiple sclerosis and black holes: connecting the pixels.

PMID- 16286538
TI  - Microarrays: applications and pitfalls.
AB  - Microarrays are simple assays that measure the relative expression levels of tens
      of thousands of genes. Excitement about their importance and potential
      contributions to biology and medicine has been intense. Nonetheless, recent
      insights into the limitations and pitfalls of microarrays have led to caution
      about data interpretation. Microarrays are very useful but they are also very
      misleading; better data analysis tools are needed to improve accuracy.

PMID- 16286539
TI  - Acute disseminated encephalomyelitis: an update.
AB  - Acute disseminated encephalomyelitis (ADEM) is a monophasic autoimmune
      demyelinating disease of the central nervous system that typically follows a
      febrile infection or a vaccination. Children are predominantly affected. A
      plethora of viral and bacterial pathogens and a number of vaccinations have been
      associated with ADEM. Experimental animal studies indicate that both primary and
      secondary autoimmune responses contribute to central nervous system inflammation
      and subsequent demyelination. The clinical diagnosis of ADEM is strongly
      suggested by a close temporal relationship between an infectious incident or an
      immunization and the onset of leukoencephalopathic neurological symptoms.
      Paraclinical tests may support the diagnosis. Particularly helpful are acute
      signs of newly developed extensive, multifocal, subcortical white matter
      abnormalities on magnetic resonance images of the brain. The cerebrospinal fluid
      may disclose a mild lymphocytic pleocytosis and elevated albumin levels.
      Oligoclonal bands are not always present in ADEM and, if so, may be transient.
      The major differential diagnosis of ADEM is multiple sclerosis. Treatment options
      for ADEM consist of anti-inflammatory and immunosuppressive agents. In general,
      the disease is self-limiting and the prognostic outcome favorable. In the absence
      of widely accepted clinical or paraclinical diagnostic guidelines, a number of
      recently conducted observational case series have substantially broadened our
      understanding about the clinical phenotype, diagnosis, and prognosis of ADEM.

PMID- 16286540
TI  - Response to interferon beta-1a treatment in African American multiple sclerosis
      patients.
AB  - BACKGROUND: African Americans (AAs) with multiple sclerosis (MS) seem to have a
      more severe disease course than white Americans (WAs). To our knowledge, it is
      not known to what extent treatment with interferon beta-1a will effect the MS
      disease course within the AA population. OBJECTIVE: To compare the response to
      treatment with interferon beta-1a between AA and WA MS patients. DESIGN: This is
      an exploratory post hoc analysis of the Evidence of Interferon Dose-Response:
      European North American Comparative Efficacy (EVIDENCE) study. SETTING: The
      EVIDENCE study is a randomized controlled trial that compared the efficacy of
      once weekly, intramuscular, 30-microg interferon beta-1a treatment with thrice
      weekly, subcutaneous, 44-microg interferon beta-1a therapy in treatment-naive MS
      subjects. PARTICIPANTS: Thirty-six AA subjects were compared with 616 WA
      subjects. MAIN OUTCOME MEASURES: The number of MS exacerbations, the proportion
      of exacerbation-free subjects, and the number of new MS lesions present on brain
      magnetic resonance imaging were compared between AA and WA subjects at 24 and 48
      weeks after initiating treatment with interferon beta-1a. RESULTS: The AA
      subjects experienced more exacerbations and were less likely to remain
      exacerbation free (statistical trends). The AA subjects developed more new MS
      lesions on T2-weighted brain magnetic resonance imaging at 48 weeks (P = .04).
      CONCLUSIONS: Despite the small sample size, AA subjects appeared less responsive
      to treatment than WA subjects on outcome measures, reaching significance only for
      T2-weighted lesion count at 48 weeks. However, it is difficult to base these
      differences solely on response to treatment given the potential differing in MS
      disease course in AA patients.

PMID- 16286541
TI  - Treatment of myasthenia gravis exacerbation with intravenous immunoglobulin: a
      randomized double-blind clinical trial.
AB  - BACKGROUND: The optimal dose of intravenous immunoglobulin (IVIG) in acute
      exacerbation of myasthenia gravis remains unknown. Increasing the treatment
      duration might provide added efficacy. OBJECTIVE: To determine the optimal dose
      of IVIG for treating myasthenia gravis exacerbation. DESIGN: Randomized double
      blind placebo-controlled multicenter trial designed to demonstrate superiority of
      the 2 g/kg dose over the 1 g/kg dose of IVIG, conducted between November 13,
      1996, and October 26, 2002. PARTICIPANTS: One hundred seventy-three patients aged
      15 to 85 years with acute exacerbation of myasthenia gravis. INTERVENTION:
      Participants were randomly assigned to receive 1 g/kg of IVIG on day 1 and
      placebo on day 2 (group 1) vs 1 g/kg of IVIG on 2 consecutive days (group 2).
      MAIN OUTCOME MEASURE: Improvement in the myasthenic muscular score after 2 weeks.
      RESULTS: The mean improvements in the myasthenic muscular scores after 2 weeks
      were 15.49 points (95% confidence interval, 12.09-18.90 points) in group 1 and
      19.33 points (95% confidence interval, 15.82-22.85 points) in group 2. However,
      the difference between the 2 groups was not significant (effect size, 3.84 [95%
      confidence interval, -1.03 to 8.71]; P = .12). CONCLUSION: This trial found no
      significant superiority of 2 g/kg over 1 g/kg of IVIG in the treatment of
      myasthenia gravis exacerbation.

PMID- 16286542
TI  - Refractory status epilepticus: effect of treatment aggressiveness on prognosis.
AB  - BACKGROUND: Administration of antiepileptic drugs for coma induction in
      refractory status epilepticus (RSE) has not been widely studied. Moreover, the
      effect on outcome of electroencephalographic (EEG) burst suppression remains
      unclear. OBJECTIVE: To investigate whether various coma-inducing options are
      associated with different prognoses after RSE. DESIGN: Retrospectively assessed
      case series. SETTING: Two tertiary referral hospitals in Boston, Mass. PATIENTS:
      Among 127 consecutive episodes (107 patients) of status epilepticus, we
      identified episodes that were refractory to first-line and second-line
      antiepileptic drugs, needing induced coma with barbiturates, propofol, or
      midazolam for clinical management. MAIN OUTCOME MEASURES: Short-term mortality
      and prevalence of return to functional baseline after the acute episode of status
      epilepticus were analyzed in relation to demographic and clinical variables and
      to treatment option (antiepileptic agents and EEG burst suppression). RESULTS:
      Forty-nine episodes of RSE (47 patients) were found, occurring more frequently in
      incident than in recurrent episodes of status epilepticus (P = .06). Mortality
      was 23% for patients with RSE and 8% for those without RSE (P = .05). Return to
      baseline occurred more often in the non-RSE group (P = .04). In 20 (61%) of 33
      monitored episodes, EEG burst suppression was achieved. Demographic data,
      clinical variables, and outcome did not differ significantly with the various
      coma-inducing agents or between episodes with and without EEG burst suppression.
      CONCLUSIONS: Refractory status epilepticus is more prevalent in incident than in
      recurrent status epilepticus and is associated with higher mortality; clinical
      status is less likely to return to baseline than with non-RSE. Outcome was
      independent of the specific coma-inducing agents used and the extent of EEG burst
      suppression, suggesting that the underlying cause represents its main
      determinant.

PMID- 16286543
TI  - Topiramate in patients with juvenile myoclonic epilepsy.
AB  - BACKGROUND: Topiramate is a broad-spectrum agent effective against primarily
      generalized tonic-clonic seizures (PGTCS) as well as partial-onset seizures.
      Juvenile myoclonic epilepsy is one of the most common idiopathic generalized
      epilepsies, with most patients experiencing PGTCS. OBJECTIVE: To evaluate
      topiramate as add-on therapy in patients with juvenile myoclonic epilepsy.
      DESIGN: Post-hoc analysis of a patient subset from 2 multicenter, double-blind,
      randomized, placebo-controlled, parallel-group trials. SETTING: Eighteen centers
      in the United States; 10 centers in Europe; 1 center in Costa Rica (primary
      trials). PATIENTS: A total of 22 patients with juvenile myoclonic epilepsy
      participating in placebo-controlled trials assessing topiramate (target dose, 400
      mg/d in adults) in inadequately controlled PGTCS. MAIN OUTCOME MEASURE: Reduction
      of PGTCS. RESULTS: A 50% or more reduction of PGTCS in 8 of 11 topiramate-treated
      patients (73%) and 2 of 11 placebo-treated patients (18%) (P = .03). Reductions
      in myoclonic, absence, and total generalized seizures were also observed,
      although topiramate vs placebo differences did not achieve statistical
      significance. CONCLUSION: As a broad-spectrum agent, topiramate is an effective
      option for patients with juvenile myoclonic epilepsy.

PMID- 16286544
TI  - Muscle coenzyme Q10 level in statin-related myopathy.
AB  - BACKGROUND: Statin drugs (3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors) reduce the level of cholesterol by inhibiting the synthesis of
      mevalonate, an intermediary in the cholesterol biosynthetic pathway. Use of
      statin drugs has been associated with a variety of skeletal muscle-related
      complaints. Coenzyme Q10 (CoQ10), a component of the mitochondrial respiratory
      chain, is also synthesized from mevalonate, and decreased muscle CoQ10
      concentration may have a role in the pathogenesis of statin drug-related
      myopathy. OBJECTIVES: To measure the CoQ10 concentration and respiratory chain
      enzyme activities in muscle biopsy specimens from 18 patients with statin drug
      related myopathy and to look for evidence of apoptosis using the TUNEL (terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end
      labeling) assay. DESIGN: An open-labeled study of CoQ10 concentration in muscle
      from patients with increased serum creatine kinase concentrations while receiving
      standard statin drug therapy. SETTING: Neuromuscular centers at 2 academic
      tertiary care hospitals. RESULTS: Muscle structure was essentially normal in 14
      patients and showed evidence of mitochondrial dysfunction and nonspecific
      myopathic changes in 2 patients each. Muscle CoQ10 concentration was not
      statistically different between patients and control subjects, but it was more
      than 2 SDs below the normal mean in 3 patients and more than 1 SD below normal in
      7 patients. There was no TUNEL positivity in any patients. CONCLUSION: These data
      suggest that statin drug-related myopathy is associated with a mild decrease in
      muscle CoQ10 concentration, which does not cause histochemical or biochemical
      evidence of mitochondrial myopathy or morphologic evidence of apoptosis in most
      patients.

PMID- 16286545
TI  - Multiple cranial nerve palsies: analysis of 979 cases.
AB  - BACKGROUND: To my knowledge, no large series of multiple cranial neuropathies is
      available. OBJECTIVES: To examine the seats and causes of multiple cranial
      neuropathies in a large group of inpatients. DESIGN: Personal case series.
      SETTING: Wards of a large municipal hospital and affiliated rehabilitation
      hospital. PATIENTS: A consecutive series of 979 unselected inpatients with
      simultaneous or serial involvement of 2 or more different cranial nerves.
      RESULTS: Cranial nerves VI (565 cases), VII (466 cases), V (353 cases), and III
      (339 cases) were most commonly affected. The locations and causes were diverse,
      with cavernous sinus (252 cases), brainstem (217 cases), and individual nerves
      (182 cases) being the most frequent sites, and tumor (305 cases), vascular
      disease (128 cases), trauma (128 cases), infection (102 cases), and the Guillain
      Barre and Fisher syndromes (91 cases total) being the most frequent causes.
      Recurrent cranial neuropathy was uncommon (43 cases, 106 episodes, 136 nerves),
      with diabetes mellitus (14 cases), self-limited unknown causes (14 cases), and
      idiopathic cavernous sinusitis (10 cases) being the usual causes. CONCLUSION:
      While the locations and causes of multiple cranial neuropathy are highly diverse,
      the fact that tumor composes more than one quarter of cases places a premium on
      prompt diagnosis.

PMID- 16286546
TI  - Neuroanatomical predictors of response to donepezil therapy in patients with
      dementia.
AB  - BACKGROUND: Patients with dementia of the Alzheimer type (DAT) respond variably
      to treatment with acetylcholinesterase inhibitors. OBJECTIVE: To determine
      whether measures of hippocampal volume and shape predict the response to
      donepezil in patients with DAT. DESIGN: T1-weighted, magnetic resonance images
      were obtained from patients with DAT, who subsequently underwent treatment with
      donepezil. Brain-mapping algorithms were used to quantify hippocampal volume and
      shape, and growth curves were used to estimate clinical outcome. SETTING: A
      referral outpatient center specializing in treatment of dementia. PATIENTS:
      Thirty-seven patients with very mild or mild DAT received donepezil therapy for
      up to 4 weeks before magnetic resonance imaging and for 24 to 96 weeks after
      magnetic resonance imaging. INTERVENTION: Donepezil, 10 mg/d. MAIN OUTCOME
      MEASURE: Rate of change in the cognitive portion of the Alzheimer's Disease
      Assessment Scale total scores. RESULTS: Smaller hippocampal volume and inward
      variation of the lateral and inferomedial portions of the hippocampal surface
      were correlated with a poorer response to donepezil therapy. CONCLUSIONS:
      Measures of hippocampal volume and surface variation can be used to predict the
      response of patients with DAT to the acetylcholinesterase inhibitor donepezil.

PMID- 16286548
TI  - Circulating levels of soluble receptor for advanced glycation end products in
      Alzheimer disease and vascular dementia.
AB  - BACKGROUND: The receptor for advanced glycation end products (RAGE) is a cell
      surface receptor that has been implicated in vascular disease and
      neurodegeneration. Low levels of its secreted isoform, soluble RAGE (sRAGE), have
      been regarded as a putative risk factor for atherosclerosis. In addition,
      administration of sRAGE has been shown to reduce development of cerebral beta
      amyloidosis in an Alzheimer disease mouse model. OBJECTIVE: To investigate the
      role of sRAGE as a biological marker for Alzheimer disease and vascular dementia.
      DESIGN: Cross-sectional study of 152 patients with a clinical diagnosis of
      Alzheimer disease, 91 with vascular dementia and 161 control subjects. MAIN
      OUTCOME MEASURE: Plasma levels of sRAGE. RESULTS: Levels of sRAGE were
      significantly reduced in the plasma of patients with Alzheimer disease compared
      with that for those with either vascular dementia (P<.05) or with controls
      (P<.001). CONCLUSIONS: Patients with Alzheimer disease have reduced levels of
      sRAGE in plasma compared with patients with vascular dementia and controls. The
      striking reduction of circulating sRAGE in Alzheimer disease further supports a
      role for the RAGE axis in this clinical entity and requires further
      investigation.

PMID- 16286547
TI  - Heterogeneity of brain glucose metabolism in mild cognitive impairment and
      clinical progression to Alzheimer disease.
AB  - BACKGROUND: Subjects with amnesic mild cognitive impairment (aMCI) may include
      patients at high risk for progression to Alzheimer disease (AD) and a population
      with different underlying pathologic conditions. OBJECTIVE: To evaluate the
      potential roles of positron emission tomography with fluorodeoxyglucose F 18
      (18FDG-PET) and memory scores in identifying subjects with aMCI and in predicting
      progression to dementia. DESIGN, SETTING, AND PATIENTS: Sixty-seven patients at
      European centers for neurologic and AD care who were diagnosed as having aMCI
      each underwent an extensive clinical and neuropsychological examination and an
      18FDG-PET study. Forty-eight subjects were followed up periodically for at least
      1 year, and progression to dementia was evaluated. MAIN OUTCOME MEASURES: Brain
      glucose metabolism and memory scores. RESULTS: Fourteen subjects with aMCI who
      converted to AD within 1 year showed bilateral hypometabolism in the inferior
      parietal, posterior cingulate, and medial temporal cortex. Subjects with "stable"
      aMCI presented with hypometabolism in the dorsolateral frontal cortex. The
      severity of memory impairment, as evaluated by the California Verbal Learning
      Test-Long Delay Free Recall scores, correlated with the following brain metabolic
      patterns: scores less than 7 were associated with a typical 18FDG-PET AD pattern,
      and scores of 7 or higher were associated with hypometabolism in the dorsolateral
      frontal cortex and no progression to AD. CONCLUSION: These data provide evidence
      for clinical and functional heterogeneity among subjects with aMCI and suggest
      that 18FDG-PET findings combined with memory scores may be useful in predicting
      short-term conversion to AD.

PMID- 16286549
TI  - Implementing diagnostic criteria and estimating frequency of mild cognitive
      impairment in an urban community.
AB  - BACKGROUND: Reported rates of mild cognitive impairment (MCI) range widely
      depending on methodologic differences, including specific sample characteristics,
      cognitive measures used, normative samples used for neuropsychological tests, and
      diagnostic criteria. OBJECTIVES: To operationalize diagnostic criteria for MCI
      and examine the frequency of MCI in ethnically and linguistically diverse elders
      (individuals older than 65 years). DESIGN: Prospective, community-based
      longitudinal cohort study. SETTING: Northern Manhattan, New York, NY.
      PARTICIPANTS: A cohort of 1315 nondemented elderly participants. MAIN OUTCOME
      MEASURE: A diagnosis of MCI was assigned retrospectively on the basis of
      comprehensive neuropsychological, functional, and neurologic assessments.
      Amnestic MCI, as well as forms of mild impairment with other cognitive
      characteristics, were classified. RESULTS: The frequency of amnestic MCI was 5.0%
      (95% confidence interval, 3.8-6.2). Other subtypes of MCI ranged in frequency
      from 2.1% to 6.2%. Mild cognitive impairment was more common among those older
      than 75 years compared with those aged 65 to 75 years. Individuals with fewer
      than 9 years of schooling were more likely to meet MCI criteria. Apolipoprotein
      (APOE) E4 allele was more frequent among those with amnestic MCI. CONCLUSIONS:
      When proper normative values are used, only age and education, and not race or
      ethnicity, are associated with higher frequency of MCI. The proportion of
      nondemented elders with isolated memory deficits is smaller than the proportion
      with deficits in multiple cognitive domains. The strong association of the APOE
      E4 allele with only amnestic MCI suggests that there are likely to be multiple
      causes of cognitive impairment and differential rates of conversion to Alzheimer
      disease within the cognitive subtypes of MCI.

PMID- 16286550
TI  - Physical activity, cognitive activity, and cognitive decline in a biracial
      community population.
AB  - BACKGROUND: Findings from studies investigating whether physical activity reduces
      the risk of cognitive decline in old age have been inconsistent. OBJECTIVE: To
      examine whether participation in physical activity by older adults reduces the
      rate of cognitive decline after accounting for participation in cognitively
      stimulating activities. DESIGN: A prospective population study conducted from
      August 1993 to January 2003, with an average follow-up of 6.4 years. SETTING: A
      biracial community population on the south side of Chicago. PARTICIPANTS:
      Participants were 4055 community-dwelling adults 65 years and older who were able
      to walk across a small room and had participated in at least 2 of the 3 follow-up
      assessments. MAIN OUTCOME MEASURE: Annual rate of cognitive change as measured by
      a global cognitive score, which consisted of averaged standardized scores from 4
      cognitive tests. RESULTS: In a mixed model adjusted for age, sex, race, and
      education, each additional physical activity hour per week was associated with a
      slower rate of cognitive decline by 0.0007 U/y (P = .04). However, with further
      adjustments (1) for participation in cognitive activities (beta = .0006, P =
      .10), (2) for depression and vascular diseases (beta = .0005, P = .19), and (3)
      by excluding participants whose global cognitive score at baseline was at or
      below the 10th percentile (beta = .0002, P = .45), the coefficients were smaller
      and no longer statistically significant. CONCLUSION: These data do not support
      the hypothesis that physical activity alone protects against cognitive decline
      among older adults.

PMID- 16286551
TI  - Postinfectious myeloradiculoneuropathy with cranial nerve involvements associated
      with human herpesvirus 7 infection.
AB  - BACKGROUND: Infection with human herpesvirus 7 (HHV-7) generally results in a
      febrile illness with accompanying exanthema subitum. OBJECTIVES: To ascertain and
      describe the role of HHV-7 in a case of acute myeloradiculoneuropathy. PATIENT: A
      previously healthy young man with complaints of motor weakness, dysphasia, and
      nasal voice. METHODS: Serological examinations were performed with the patient's
      serum. We also examined virus genome DNA in cerebrospinal fluid by regular and
      real-time polymerase chain reaction. Moreover, we checked the antiganglioside
      antibody level in the patient's serum samples by the immunoblot analysis.
      RESULTS: Serological studies revealed significant change in titers of antibodies
      against cytomegalovirus, Epstein-Barr virus, and HHV-7, but only HHV-7 genome was
      detected in the cerebrospinal fluid, with its disappearance after therapy. No
      antiganglioside antibody was detected in the patient's serum. CONCLUSION: The
      unique clinical picture of the present patient might be closely related to the
      reactivation of HHV-7 in the nervous system.

PMID- 16286553
TI  - Bilateral third nerve palsy and temporal arteritis.
AB  - BACKGROUND: Bilateral oculomotor palsy is a rare manifestation of temporal
      arteritis, and to our knowledge only 1 case has been described in the literature.
      OBJECTIVE: To investigate a possible case of temporal arteritis in a patient with
      bilateral third nerve palsy. DESIGN: Case report and review. SETTING: University
      hospital. PATIENT: A 65-year-old man had subacute pupil-sparing bilateral third
      nerve palsy. RESULTS: Temporal artery biopsy findings and response to
      corticosteroids are consistent with temporal arteritis. CONCLUSION: Temporal
      arteritis is a rare cause of ophthalmoplegia in elderly persons and may be
      unrecognized.

PMID- 16286552
TI  - Mechanical thrombectomy following intravenous thrombolysis in the treatment of
      acute stroke.
AB  - BACKGROUND: The efficacy of intravenous thrombolytics in acute stroke is limited
      by low rates of recanalization of occluded arteries. Treatment with intravenous
      thrombolytics followed by mechanical thrombectomy is a novel approach that may
      increase recanalization rates without compromising time to initiation of
      treatment. OBJECTIVES: To report our experience with 2 patients who received this
      combination therapy and outline plans for a prospective pilot study. DESIGN AND
      SETTING: Case studies at a university hospital. INTERVENTIONS: Patients treated
      with intravenous thrombolytics within 3 hours of symptom onset subsequently
      underwent computed tomographic angiography. If an occlusion of a proximal
      cerebral vessel was shown by a computed tomographic angiogram, mechanical
      thrombectomy was performed. Patients were observed for 1 month after treatment.
      MAIN OUTCOME MEASURES: National Institutes of Health Stroke Scale (NIHSS) score.
      RESULTS: The computed tomographic angiography of 2 patients showed complete
      occlusion of the M1 branch of the middle cerebral artery following administration
      of intravenous thrombolytics. The NIHSS scores were 21 and 13. In both cases,
      blood flow through the occluded artery was restored with mechanical thrombectomy
      and dramatic neurologic improvement occurred. There were no complications. The
      NIHSS scores were 0 and 2 at 1-month follow-up. CONCLUSION: Treatment with
      intravenous thrombolytics followed by mechanical thrombectomy may improve
      outcomes in acute stroke patients and a pilot safety trial is warranted.

PMID- 16286554
TI  - Petrositis in Ramsay Hunt syndrome with multiple cranial neuropathies.

PMID- 16286555
TI  - Hypertrophy of the nerve roots of the cauda equina as a paraneoplastic
      manifestation of lymphoma.

PMID- 16286556
TI  - Sickle cell trait is a risk factor for early stroke.

PMID- 16286557
TI  - Sickle cell trait is not a risk factor for stroke.

PMID- 16286558
TI  - Sickle cell trait: innocent until proven guilty.

PMID- 16286559
TI  - The trouble with eponyms.

PMID- 16286560
TI  - Earlier Alzheimer onset in Latino persons: ethnic difference vs selection bias.

PMID- 16286561
TI  - High folic acid intake is not a risk factor for cognitive decline:
      misinterpretation of results.

PMID- 16286562
TI  - The terms Latino and Anglo and tendency to early Alzheimer disease.

PMID- 16286563
TI  - The prothrombotic paradox of hypertension: role of the renin-angiotensin and
      kallikrein-kinin systems.
AB  - Despite increased pulsatile stress, thrombotic rather than hemorrhagic events
      represent a major complication of hypertension. The pathophysiology of thrombosis
      in hypertension involves the interaction among vascular endothelium and
      particularly the renin-angiotensin and kallikrein-kinin systems. Because
      hypertension is often associated with some degree of inflammation, the
      combination of chronic inflammation and chronic shear stress may convert the
      normal anticoagulant endothelium into a procoagulant surface, expressing tissue
      factor. Activation of the renin-angiotensin system leads to activation of nuclear
      factor kappaB-dependent proinflammatory genes, also accelerating the expression
      of tissue factor. Renin-angiotensin and kallikrein-kinin systems interact at
      several levels to modulate coagulation, fibrinolysis, and vasodilatation in such
      a way that these 2 systems could have a major influence on the occurrence of
      thrombotic complications. Treatment with angiotensin-converting enzyme inhibitors
      and angiotensin II type 1 receptor antagonists may favorably influence the
      balance between the renin-angiotensin and kallikrein-kinin axis, regulating blood
      pressure as well as reducing the risk of thrombosis, which may explain part of
      the clinical efficacy of these drugs.

PMID- 16286564
TI  - The angiotensin II type 2 receptor causes constitutive growth of cardiomyocytes
      and does not antagonize angiotensin II type 1 receptor-mediated hypertrophy.
AB  - Angiotensin II (Ang II) has important actions on the heart via type 1 (AT1) and
      type 2 (AT2) receptors. The link between AT1 receptor activation and the
      hypertrophy of cardiomyocytes is accepted, whereas the contribution of the AT2
      receptor, which reportedly antagonizes the AT1 receptor, is contentious. This
      ambiguity is primarily based on in vivo approaches, in which the direct effect of
      the AT2 receptor and its modulation of the AT1 receptor (at the level of the
      cardiomyocyte) are difficult to establish. In this study, we used adenoviruses
      encoding AT1 and AT2 to coexpress these receptors in isolated cardiomyocytes,
      allowing a direct examination of the consequence of varying AT1/AT2 stoichiometry
      on cardiomyocyte hypertrophy. In myocytes expressing only the AT1 receptor, Ang
      II stimulation promoted robust hypertrophy (increased protein:DNA ratio and
      phenotypic changes) via activation of mitogen-activated protein kinases (MAPKs).
      Titration of the AT2 receptor against the AT1 receptor did not inhibit Ang II
      mediated cardiomyocyte hypertrophy. Instead, basal and Ang II-mediated
      hypertrophy was increased in line with the amplified expression of the AT2
      receptor, indicating a capacity for the AT2 receptor to enhance basal
      cardiomyocyte growth. Indeed, expression of the AT2 receptor alone resulted in
      hypertrophy; remarkably, this was unaffected by Ang II stimulation or the AT2
      receptor-specific ligands PD123319 and CGP42112. Although previous studies have
      indicated that the AT2 receptor can antagonize MAPK activation via the AT1
      receptor, we found no evidence for this in cardiomyocytes. Thus, the AT2 receptor
      promotes ligand-independent, constitutive cardiomyocyte hypertrophy and does not
      directly antagonize the AT1 receptor in this setting.

PMID- 16286565
TI  - Mechanisms of mineralocorticoid action.
AB  - Sodium transport in epithelial tissues is regulated by the physiological
      mineralocorticoid aldosterone. The response to aldosterone is mediated by the
      mineralocorticoid receptor (MR), for which the crystal structure of the ligand
      binding domain has recently been established. The classical mode of action for
      this receptor involves the regulation of gene transcription. Several genes have
      now been shown to be regulated by aldosterone in epithelial tissues. Of these,
      the best characterized is serum- and glucocorticoid-regulated kinase, which
      increases sodium influx through the epithelial sodium channel. Turnover of these
      channels in the cell membrane is mediated by Nedd4-2, a ubiquitin protein ligase;
      serum- and glucocorticoid-regulated kinase interacts with and phosphorylates
      Nedd4-2, thereby rendering it unable to bind the sodium channels. In
      nonepithelial tissues, particularly the cardiovascular system, aldosterone also
      has direct effects, activating an inflammatory cascade, leading to cardiac
      fibrosis. A critical role for the MR in cardiovascular disease has now been
      demonstrated by the beneficial response to MR blockade in 2 large clinical trials
      in patients with cardiac failure. It is these nonepithelial actions of MR
      activation that need to be exploited for the development of antagonists that
      target the cardiovascular system while avoiding the undesirable side effects of
      renal MR blockade.

PMID- 16286567
TI  - Calcitonin gene-related peptide and sympathetic nervous system in hypertension
      induced renal damage.

PMID- 16286568
TI  - The continuing saga of the AT2 receptor: a case of the good, the bad, and the
      innocuous.

PMID- 16286569
TI  - Muscle sympathetic nerve activity during wakefulness in heart failure patients
      with and without sleep apnea.
AB  - Sympathetic activation and sleep apnea are present in most patients with
      symptomatic systolic heart failure (HF). Acutely, obstructive and central apneas
      increase muscle sympathetic activity (MSNA) during sleep by eliciting recurrent
      hypoxia, hypercapnia, and arousal. In obstructive sleep apnea patients with
      normal systolic function, this increase persists after waking. Whether coexisting
      sleep apnea augments daytime MSNA in HF is unknown. We tested the hypothesis that
      its presence exerts additive effects on MSNA during wakefulness. Overnight sleep
      studies and morning MSNA recordings were performed on 60 subjects with ejection
      fraction <45%. Of these, 43 had an apnea-hypopnea index > or =15 per hour.
      Subjects with and subjects without sleep apnea were similar for age, ejection
      fraction, HF etiology, body mass index, blood pressure, and heart rate. Daytime
      MSNA was significantly higher in those with sleep apnea (76+/-2 versus 63+/-4
      bursts per 100 heartbeats [mean+/-SEM], P=0.005; 58+/-2 versus 50+/-3 bursts/min,
      P=0.037), irrespective of its etiology (the mean difference for central sleep
      apnea was 17 bursts per 100 heartbeats; n=14; P=0.006; and for obstructive sleep
      apnea, 11 bursts per 100 heartbeats; n=29; P=0.032). In a subgroup (n=8),
      treatment of obstructive sleep apnea lowered MSNA by 12 bursts per 100 heartbeats
      (P=0.003). Convergence of independent excitatory influences of HF and sleep apnea
      on central sympathetic neurons results in higher MSNA during wakefulness in HF
      patients with coexisting sleep apnea. This additional stimulus to central
      sympathetic outflow may accelerate the progression of HF; its attenuation by
      treatment of sleep apnea represents a novel nonpharmacological opportunity.

PMID- 16286570
TI  - A population association study of angiotensinogen polymorphisms and haplotypes
      with left ventricular phenotypes.
AB  - Several studies have shown an association between single nucleotide polymorphisms
      (SNPs) in the angiotensinogen (AGT) gene and hypertension. Because hypertension
      is a risk factor for left ventricular (LV) hypertrophy and because evidence from
      animal models suggests that AGT may play a role in the growth and hypertrophy of
      the heart, we chose to conduct a population association study examining the
      relationship of 10 SNPs in the AGT gene with 7 different LV phenotypes measured
      by echocardiography. Participants (336 whites and 441 blacks) were drawn from the
      Hypertension Genetic Epidemiology Network (HyperGEN) study. Individuals were
      genotyped for 10 previously identified SNPs within the AGT gene. SNP genotype
      results were regressed against continuous LV phenotypes to test associations
      separately in each race. Using a cutoff of P<0.005 to account for multiple
      testing, we found 1 SNP (rs943580) significantly associated with transmitral
      early peak filling velocity (MVE) in the black population. We also used Phase
      2.0.2 to reconstruct haplotypes from genotype data. Using the same cutoff of
      P<0.005, we found no haplotypes to be significantly associated with the LV
      phenotypes. To better understand the association between rs943580 and MVE, we
      examined AGT haplotype associations with MVE. The single SNP association was
      driven by a large group of SNPs in high linkage disequilibrium that includes the
      promoter SNP rs5051.

PMID- 16286571
TI  - Lack of inducible NO synthase reduces oxidative stress and enhances cardiac
      response to isoproterenol in mice with deoxycorticosterone acetate-salt
      hypertension.
AB  - Although NO derived from endothelial NO synthase (eNOS) is thought to be
      cardioprotective, the role of inducible NO synthase (iNOS) remains controversial.
      Using mice lacking iNOS (iNOS-/-), we studied (1) whether development of
      hypertension, cardiac hypertrophy, and dysfunction after deoxycorticosterone
      acetate (DOCA)-salt would be less severe compared with wild-type controls (WT;
      C57BL/6J), and (2) whether the cardioprotection attributable to lack of iNOS is
      mediated by reduced oxidative stress. Mice were uninephrectomized and received
      either DOCA-salt (30 mg/mouse SC and 1% NaCl+0.2% KCl in drinking water) or
      vehicle (tap water) for 12 weeks. Systolic blood pressure (SBP) was measured
      weekly. Left ventricular (LV) ejection fraction (EF) by echocardiography and
      cardiac response to isoproterenol (50 ng/mouse IV) were studied at the end of the
      experiment. Expression of eNOS and iNOS as well as the oxidative stress markers 4
      hydroxy-2-nonenal (4-HNE, a marker of lipid peroxidation) and nitrotyrosine (a
      marker for peroxynitrite) were determined by Western blot and immunohistochemical
      staining, respectively. DOCA-salt increased SBP and LV weight similarly in both
      strains and decreased EF in WT but not in iNOS-/-. Cardiac contractile and
      relaxation responses to isoproterenol were greater, 4-HNE and nitrotyrosine
      levels were lower, and eNOS expression tended to be higher in iNOS-/-. We
      conclude that lack of iNOS leads to better preservation of cardiac function,
      which may be mediated by reduced oxidative stress and increased eNOS; however, it
      does not seem to play a significant role in preventing DOCA-salt-induced
      hypertension and hypertrophy.

PMID- 16286572
TI  - Calcium inhibits renin gene expression by transcriptional and posttranscriptional
      mechanisms.
AB  - The aim of this study was to investigate the role of cytosolic calcium for renin
      gene expression in juxtaglomerular cells. For this purpose, we used the
      immortalized juxtaglomerular mouse cell line As4.1. To increase cytosolic calcium
      concentration, we treated the cells with thapsigargin and cyclopiazonic acid,
      inhibitors of the endoplasmatic reticulum Ca- ATPase. Thapsigargin and
      cyclopiazonic acid inhibited renin gene expression in a characteristic time and
      concentration-dependent manner. This effect was concentration-dependently blocked
      by BAPTA-AM, an intracellular Ca2+ chelator. Pharmacological blocking of protein
      kinase C activity by calphostin, Go6976, and Go6983 did not change the effect of
      thapsigargin on renin gene expression. Experiments with renin1C-promoter-reporter
      constructs revealed that thapsigargin inhibited renin gene transcription.
      Analysis of deletion constructs of the renin1C promoter indicated that regulatory
      elements involved in the calcium-mediated inhibition of renin gene transcription
      are located in the enhancer region of the renin gene and that > or =3
      transcription factor-binding sites are involved in this process. In addition,
      thapsigargin reduced the renin mRNA half-life from 10 hours (control conditions)
      to 4 hours. Knockdown studies with small interfering RNA directed to dynamin-1
      mRNA revealed that dynamin-1 is likely to be involved in the calcium-mediated
      destabilization of renin mRNA. These data suggest that calcium inhibits renin
      gene expression in juxtaglomerular cells via a concerted action of inhibition of
      renin gene transcription and destabilization of renin mRNA.

PMID- 16286573
TI  - Epistasis, not numbers, regulates functions of clustered Dahl rat quantitative
      trait loci applicable to human hypertension.
AB  - Quantitative trait loci (QTLs) for blood pressure (BP) were found on chromosome
      10 of Dahl salt-sensitive rats and are potentially important to human essential
      hypertension. But their identities and how they influence BP together were not
      known. Presently, we first fine mapped existing QTLs, C10QTL1, C10QTL2, and
      C10QTL3, by constructing congenic strains. In the process, a new QTL, C10QTL4,
      was identified. Because the intervals harboring C10QTL1 and C10QTL4 contain a
      maximum of 16 and 10 possible genes, respectively, a limited number of specific
      gene targets has been identified to be QTLs residing in human homologous regions
      on chromosome 17. Moreover, because none of these candidates encodes a gene known
      to influence BP, the 2 QTLs will represent novel genes for BP regulations.
      Second, we used congenic strains with QTL combinations to analyze the
      interactions between the QTLs. Consequently, a double combination of C10QTL4 and
      C10QTL1 possessed the same BP as each of the 2 QTLs alone. BP of a triple
      combination of C10QTL4, C10QTL1, and C10QTL3 was not different from BP of the
      C10QTL4 and C10QTL1 double combination. These results demonstrate that C10QTL4,
      C10QTL1, and C10QTL3 are epistatic to one another in their BP effects. In
      contrast, when adding C10QTL2 into the triple formation of the 3 QTLs above to
      create a quadruple QTL combination, BP increased proportionately, indicating that
      C10QTL2 acts independently of C10QTL4, C10QTL1, and C10QTL3. The epistatic and
      additive interactions uncovered in the animal model will help elucidate similar
      interactions playing a role in human essential hypertension.

PMID- 16286574
TI  - Genome-wide linkage analysis for loci affecting pulse pressure: the Family Blood
      Pressure Program.
AB  - Pulse pressure, the difference between systolic and diastolic blood pressure, is
      an independent risk factor for cardiovascular disease. Increased pulse pressure
      reflects reduced compliance of arteries and is a marker of atherosclerosis. To
      locate genes that affect pulse pressure, a genome-wide linkage scan for
      quantitative trait loci influencing pulse pressure was performed using variance
      components methods as implemented in sequential oligogenic linkage analysis
      routines. The analysis sample included 10 798 participants in 3320 families who
      were recruited as part of the Family Blood Pressure Program and were phenotyped
      with an oscillometric blood pressure measurement device using a consistent
      protocol across centers. Pulse pressure was adjusted for the effects of sex, age,
      age2, age-by-sex interaction, age2-by-sex interaction, body mass index, and field
      center to remove sources of variation other than the genetic effects related to
      pulse pressure. Significant linkage was observed on chromosome 18 (logarithm of
      odds [LOD]=3.2) in a combined racial sample, chromosome 20 (LOD=4.4), and 17
      (LOD=3.6) in Hispanics, chromosome 21 (LOD=4.3) in whites, chromosome 19
      (LOD=3.1) in a combined sample of blacks and whites, and chromosome 7 (logarithm
      of odds [LOD]=3.1) in blacks from the GenNet Network. Our genome scan shows
      significant evidence for linkage for pulse pressure in multiple areas of the
      genome, supporting previous published linkage studies. The identification of
      these loci for pulse pressure and the apparent congruence with other blood
      pressure phenotypes provide increased support that these regions contain genes
      influencing blood pressure phenotypes.

PMID- 16286575
TI  - Body mass index and angiotensin-dependent control of the renal circulation in
      healthy humans.
AB  - Obesity is increasingly recognized as a risk factor for renal disease, but the
      mechanism is unclear. Renal plasma flow response to captopril, as an index of
      renin-angiotensin system activity, was measured by para-aminohippurate clearance
      technique in 100 healthy, normotensive subjects in balance on a high-salt diet.
      Of the 100 subjects, body mass index exceeded 25 in 56 and exceeded 30 in 22. The
      average vasodilator response to captopril was 27+/-7 mL/min per 1.73 m2
      (P<0.0001). After adjustment for other predictors of the renal plasma flow
      response to captopril using a multivariate linear regression model, there was a
      highly significant relationship between age- and plasma renin activity-adjusted
      body mass index and the renal plasma flow response to captopril; however, a
      quadratic model provided a substantially better fit (r=0.55; P<0.0001; P=0.03
      versus linear correlation). The strong association between increasing body mass
      index and angiotensin-dependent control of the renal circulation suggests that
      this may be a mechanism by which obesity contributes to renal disease. Weight
      loss should be considered in the overweight or obese patient for renal
      protection.

PMID- 16286576
TI  - Urinary albumin excretion and carotid intima-media thickness.

PMID- 16286577
TI  - Reduction of microalbuminuria by beta blockers: beyond renin-angiotensin system
      blockade.

PMID- 16286580
TI  - Chocolate consumption and incidence of hypertension.

PMID- 16286578
TI  - Differential effects of beta-blockers on albuminuria in patients with type 2
      diabetes.
AB  - Increases in the cardiovascular risk marker microalbuminuria are attenuated by
      blood pressure reduction using blockers of the renin-angiotensin system. Such
      changes in microalbuminuria have not been observed when beta-blockers are used. A
      prespecified secondary end point of the Glycemic Effects in Diabetes Mellitus
      Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial was to examine
      the effects of different beta-blockers on changes in albuminuria in the presence
      of renin-angiotensin system blockade. Participants with hypertension and type 2
      diabetes were randomized to either metoprolol tartrate (n=737) or carvedilol
      (n=498) in blinded fashion after a washout period of all antihypertensive agents
      except for angiotensin-converting enzyme inhibitors or angiotensin receptor
      blockers. Blinded medication was titrated to achieve target blood pressure, with
      a-5 month follow-up period. The current analysis examined microalbuminuria, using
      spot urine albumin:creatinine, in participants who had values at screening and
      trial end. A greater reduction in microalbuminuria was observed for those
      randomized to carvedilol (-16.2%Delta; 95% confidence interval, -25.3, -5.9;
      P=0.003). Of those with normoalbuminuria at baseline, fewer progressed to
      microalbuminuria on carvedilol versus metoprolol (20 of 302 [6.6%] versus 48 of
      431 [11.1%], respectively; P=0.03). Microalbuminuria development was not related
      to differences in blood pressure or achievement of blood pressure goal (68%
      carvedilol versus 67%, metoprolol). Presence of metabolic syndrome at baseline
      was the only independent predictor of worsening albuminuria throughout the study
      (P=0.004). Beta-blockers have differential effects on microalbuminuria in the
      presence of renin-angiotensin system blockade. These differences cannot be
      explained by effects on blood pressure or alpha1-antagonism but may relate to
      antioxidant properties of carvedilol.

PMID- 16286582
TI  - Thrombophilia and severe preeclampsia: time to screen and treat in future
      pregnancies?

PMID- 16286581
TI  - Adenosine-stimulated atrial natriuretic peptide release through A1 receptor
      subtype.
AB  - Adenosine acts as an important protector of ischemic myocardium through coronary
      vasodilation and the depression of cardiac contractility. The protective effect
      of adenosine may partly relate to the cardiac hormone atrial natriuretic peptide
      (ANP). The aim of the present study was to investigate the effects of adenosine
      and the adenosine receptor subtype on atrial hemodynamics and ANP release using
      isolated perfused beating rat atria. Adenosine, a nonselective adenosine receptor
      agonist, increased the ANP release with negative inotropism in a dose-dependent
      manner. Adenosine-stimulated ANP release was attenuated by a selective A1
      antagonist but not A(2A) antagonist or A3 antagonist. The order of potency of the
      various agonists for the ANP release was A1 agonists>>A3 agonist=adenosine>A(2A)
      agonist. The order of potency for the negative inotropy was A1
      agonists>adenosine=A(2A) agonist>A3 agonist. The negative inotropism and ANP
      release by a specific A1 agonist (N6-cyclopentyl-adenosine) were also attenuated
      by A1 antagonist but not A(2A) antagonist or A3 antagonist. Treatment with A1
      agonist resulted in a decrease of cAMP contents in atria and perfusates. The
      agonist-stimulated ANP release was significantly attenuated in the presence of
      forskolin, isoproterenol 8-Br-cAMP, or an adenylyl cyclase inhibitor. These
      results suggest that the A1 receptor subtype is responsible for the adenosine
      induced ANP release and negative inotropism through adenylyl cyclase-cAMP
      pathway.

PMID- 16286583
TI  - Acute neurocardiogenic injury after subarachnoid hemorrhage.
AB  - BACKGROUND: Left ventricular (LV) systolic dysfunction has been reported in
      humans with subarachnoid hemorrhage (SAH), and its underlying pathophysiology
      remains controversial. Possible mechanisms include myocardial ischemia versus
      excessive catecholamine release from sympathetic nerve terminals. METHODS AND
      RESULTS: For 38 months, echocardiography and myocardial scintigraphy with
      technetium sestamibi (MIBI) and meta-[(123)I]iodobenzylguanidine (MIBG) were
      performed on 42 patients admitted with SAH to assess myocardial perfusion and
      sympathetic innervation, respectively. A blinded observer interpreted the
      scintigraphic images. Cardiac troponin I (cTI) was measured to quantify the
      degree of myocyte necrosis. Blinded observers calculated the LV ejection fraction
      and graded each LV segment as normal (score=1), hypokinetic (score=2), or
      akinetic (score=3). A wall-motion score was calculated by averaging the sum of
      the 16 segments. All subjects with interpretable scans (N=41) had normal MIBI
      uptake. Twelve subjects had either global (n=9) or regional (n=3) absence of MIBG
      uptake. In comparison with patients with normal MIBG uptake, those with evidence
      of functional denervation were more likely to have LV regional wall-motion
      abnormalities (92% versus 52%, P=0.030) and cTI levels >1 microg/L (58% versus
      21%, P=0.029). CONCLUSIONS: LV systolic dysfunction in humans with SAH is
      associated with normal myocardial perfusion and abnormal sympathetic innervation.
      These findings may be explained by excessive release of norepinephrine from
      myocardial sympathetic nerves, which could damage both myocytes and nerve
      terminals.

PMID- 16286584
TI  - Prognosis of carcinoid heart disease: analysis of 200 cases over two decades.
AB  - BACKGROUND: The long-term prognosis of patients who develop carcinoid heart
      disease and the effect of cardiac surgery on outcome are not well established.
      METHODS AND RESULTS: In this retrospective study, we identified 200 patients with
      carcinoid syndrome referred for echocardiography in whom the diagnosis of
      carcinoid heart disease was confirmed. Patients were divided into 3 groups of
      similar size according to the date from first diagnosis of carcinoid heart
      disease. Group A comprised patients diagnosed from 1981 through June 1989; group
      B, diagnosed July 1989 through May 1995; and group C, June 1995 through 2000. The
      end point was all-cause mortality. Median survival was significantly lower in
      group A (1.5 years, 95% CI 1.1 to 1.9 years) compared with groups B (3.2, 95% CI
      1.3 to 5.1 years) and C (4.4, 95% CI 2.4 to 7.1 years; P=0.009). In a
      multivariate model adjusted for treatment and clinical characteristics, the risk
      of death in groups B (hazard ratio 0.67, 95% CI 0.46 to 0.99, P=0.04) and C
      (hazard ratio 0.61, 95% CI 0.39 to 0.92, P=0.006) was significantly reduced
      relative to group A. Cardiac surgery was performed in 87 patients. When cardiac
      surgery was included as a time-dependent covariate in a multivariate analysis, it
      was associated with a risk reduction of 0.48 (95% CI 0.31 to 0.73, P<0.001),
      whereas the time period of diagnosis was no longer significant. CONCLUSIONS: The
      prognosis of patients with recognized carcinoid heart disease has improved over
      the past 2 decades at our institution. This change in survival may be related to
      valve replacement surgery.

PMID- 16286585
TI  - Obesity and risk of new-onset atrial fibrillation after cardiac surgery.
AB  - BACKGROUND: New-onset postoperative atrial fibrillation (AF) is a common
      complication of cardiac surgery that has substantial effects on outcomes. In the
      general (nonsurgical) adult population, AF has been linked to increasing obesity,
      which correlates with left atrial enlargement. It is not known whether
      postoperative AF is similarly linked to obesity. METHODS AND RESULTS: This was a
      retrospective analysis of the incidence of AF in terms of body mass index (BMI).
      A total of 8051 consecutive cardiac surgery patients (1994 to 2004; mean age 64
      [SD 11] years; 5372 men [67%]) who were free of any history of preoperative AF or
      flutter were included in the analysis. This series included 3164 obese patients
      (39%; median age 62 years) and 4887 nonobese patients (61%; median age 66 years),
      who were further divided on the basis of BMI (kg/m2) into 6 groups: BMI <22
      kg/m2, 22< or =BMI< or =25 kg/m2 (normal), 25<BMI> or =30 kg/m2 (overweight),
      30<BMI > or =35 kg/m2 (obese I), 35<BMI> or =40 kg/m2 (obese II), and BMI >40
      kg/m2 (obese III). Unadjusted AF incidence was similar in obese and nonobese
      patients (n=742 [23.5%] versus n=1068 [21.9%], respectively; P=0.099). Covariate
      adjusted ORs for AF were systematically greater for larger patients than for
      patients in the normal group (adjusted OR [95% CI]=1.18 [1.00 to 1.40], 1.36
      [1.14 to 1.63], 1.69 [1.35 to 2.11], and 2.39 [1.81 to 3.17] for overweight,
      obese I, obese II, and obese III, respectively). Other AF predictors included age
      (adjusted OR=1.52 [95% CI 1.46 to 1.58] per 10 years), mitral valve surgery
      (adjusted OR=2.42 [95% CI 1.92 to 3.06]), aortic valve surgery (adjusted OR=1.79
      [95% CI 1.45 to 2.22]), chronic obstructive pulmonary disease (adjusted OR=1.28
      [95% CI 1.12 to 1.46]), male gender (adjusted OR=1.24 [95% CI 1.10 to 1.40]),
      preoperative beta-blocker use (adjusted OR=1.17 [95% CI 1.05 to 1.32]), vascular
      disease (adjusted OR=1.18 [95% CI 1.05 to 1.32]), white race (adjusted OR=1.33
      [95% CI 1.07 to 1.66]), history of arrhythmia other than AF/flutter (adjusted
      OR=0.80 [95% CI 0.68 to 0.96]), ejection fraction <40% (adjusted OR=1.16 [95% CI
      1.03 to 1.31]), left main disease (adjusted OR=1.15 [95% CI 1.00 to 1.32]), and
      off-pump surgery (adjusted OR=0.61 [95% CI 0.44 to 0.83]). The obesity-AF
      association was confirmed in 4 1-to-1 propensity-matched obese versus nonobese
      comparisons and in 2 separate derivation/validation subcohort analyses.
      CONCLUSIONS: Obesity is an important determinant of new-onset AF after cardiac
      surgery. Future postoperative AF risk models should incorporate BMI or obesity
      levels. Studies examining the efficacy of AF-minimizing prophylactic
      interventions in high-BMI patients, particularly in the elderly, may be
      warranted.

PMID- 16286587
TI  - Resting myocardial blood flow is impaired in hibernating myocardium: a magnetic
      resonance study of quantitative perfusion assessment.
AB  - BACKGROUND: Although impairment in perfusion reserve is well recognized in
      hibernating myocardium, there is substantial controversy as to whether resting
      myocardial blood flow (MBF) is reduced in such circumstances. Quantitative first
      pass cardiovascular magnetic resonance (CMR) perfusion imaging allows absolute
      quantification of MBF. We hypothesized that MBF assessed at rest by quantitative
      CMR perfusion imaging is reduced in hibernating myocardium. METHODS AND RESULTS:
      Twenty-seven patients with 1 or 2-vessel coronary disease and at least 1
      dysfunctional myocardial segment undergoing PCI were studied with preprocedure,
      early (24 hours), and late (9 months) postprocedure CMR imaging. First-pass
      perfusion images at rest were acquired in 3 short-axis planes by use of a T1
      weighted turboFLASH sequence. In each slice, MBF was determined for 8 myocardial
      segments in mL . min(-1) . g(-1) by deconvolution of signal intensity curves with
      an arterial input function measured in the left ventricular blood pool. Cine MRI
      for assessment of global and segmental function and delayed enhancement MRI for
      detection of viability were also obtained. All coronary lesions were 80% to 95%
      stenosis in severity. Over all segments, mean MBF normalized by rate-pressure
      product ("corrected MBF") was 1.2+/-0.3 mL . min(-1) . g(-1) . (mm Hg .
      bpm/10(4))(-1) in segments without significant coronary stenosis and 0.7+/-0.2 mL
      . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in segments with coronary stenosis
      before PCI (mixed model controlling for slice and segment z=-23.9, P<0.001).
      Early after the procedure, the MBF was 1.2+/-0.2 mL . min(-1) . g(-1) . (mm Hg .
      bpm/10(4))(-1) in revascularized segments and 1.3+/-0.2 mL . min(-1) . g(-1) .
      (mm Hg . bpm/10(4))(-1) in nondiseased segments (z=-6.1, P<0.001). Late after
      PCI, the systolic wall thickening and end-diastolic wall thickness both increased
      significantly more (both P<0.001) in the myocardial segments subtended by severe
      coronary stenosis (8+/-17% to 40+/-19% and 6.5+/-1.1 to 9.3+/-2 mm, respectively)
      than in the myocardial segments supplied by nondiseased vessels. Mean MBF in
      dysfunctional segments with significantly improved contraction after
      revascularization was 0.8+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1)
      before PCI and 1.2+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) after PCI
      (z=2.0, P=0.04). CONCLUSIONS: CMR perfusion imaging detects impaired resting MBF
      in hibernating myocardial segments.

PMID- 16286586
TI  - Clinical efficacy of polymer-based paclitaxel-eluting stents in the treatment of
      complex, long coronary artery lesions from a multicenter, randomized trial:
      support for the use of drug-eluting stents in contemporary clinical practice.
AB  - BACKGROUND: Intracoronary polymer-based stent delivery of paclitaxel has been
      shown to be effective in reducing restenosis in simple coronary lesions, but the
      evidence base for contemporary use in longer, more complex coronary stenoses is
      lacking. METHODS AND RESULTS: TAXUS VI is a prospective, multicenter, double
      blind, randomized trial assessing clinical and angiographic outcomes of the TAXUS
      Moderate Release paclitaxel-eluting stent in the treatment of long, complex
      coronary artery lesions. Four hundred forty-eight patients at 44 sites were
      randomized (1:1) between a drug-eluting TAXUS Express2 and an uncoated Express2
      control stent. Per protocol, the 9-month follow-up included an angiographic
      reevaluation in all patients. The primary end point was the rate of target-vessel
      revascularization 9 months after the study procedure; secondary end points
      included the rate of target-lesion revascularization and binary restenosis at
      follow-up. Mean lesion length in the study was 20.6 mm, with a mean stent-covered
      length of 33.4 mm. Of all lesions, 55.6% were classified as complex lesions (type
      C of the AHA/ACC classification). At 9 months, target-vessel revascularization
      was 9.1% in the TAXUS group and 19.4% in the control group (P=0.0027; relative
      reduction, 53%). Target-lesion revascularization was reduced from 18.9% to 6.8%,
      respectively (P=0.0001). The incidence of major adverse cardiac events was
      similar in the 2 groups, 16.4% and 22.5% in TAXUS and control, respectively
      (P=0.12), including comparable rates for acute myocardial infarction. Binary
      restenosis in the stented area was reduced from 32.9% in the control group to
      9.1% in the TAXUS patients (P<0.0001). CONCLUSIONS: The finding that the TAXUS
      Moderate Release stent system is safe and effective in the treatment of long,
      complex coronary artery lesions provides the evidence base for the more
      widespread use of drug-eluting stents in contemporary clinical practice.

PMID- 16286588
TI  - Angiotensin type 2 receptor is expressed in murine atherosclerotic lesions and
      modulates lesion evolution.
AB  - BACKGROUND: In the vasculature, the angiotensin type 2 (AT2) receptor (AT2R)
      exerts antiproliferative, antifibrotic, and proapoptotic effects. Normal adult
      animals have low AT2R expression; however, vascular injury and exposure to
      proinflammatory cytokines augment AT2R levels. We hypothesized that AT2R
      expression increases during initiation and progression of atherosclerosis.
      METHODS AND RESULTS: Atherosclerotic lesions of apolipoprotein (Apo) E(-/-) mice
      contained AT2Rs, measured by real-time polymerase chain reaction and confirmed by
      immunohistochemistry. To test the consequences of this expression, male ApoE(-/
      ), angiotensin II type 2 receptor-deficient (Agtr2-), and ApoE(-/-), wild-type
      (Agtr2+) mice consumed a high-cholesterol diet from 4 weeks of age. Ten weeks
      later, overall area and cellular composition of aortic arch lesions did not
      differ significantly among genotypes. After 16 weeks, ApoE(-/-)/Agtr2+, but not
      ApoE(-/-)/Agtr2- mice had dramatic decreases in percent positive area of
      macrophages, smooth muscles, lipids, and collagen. Diminished bromodeoxyuridine
      incorporation and increased TUNEL staining accompanied these decreases.
      CONCLUSIONS: Thus, loss of AT2R during the evolution of atherosclerotic lesions
      augmented the extent of cellularity of atherosclerotic lesions, establishing AT2R
      as a modulator of atherogenesis.

PMID- 16286589
TI  - Myocardial ischemia induces interleukin-6 and tissue factor production in
      patients with coronary artery disease: a dobutamine stress echocardiography
      study.
AB  - BACKGROUND: Interleukin-6 (IL-6) and macrophage colony stimulating factor plasma
      levels are elevated in acute coronary syndromes. IL-6 has an inherent negative
      inotropic action and, with tissue factor (TF), mediates the ischemia-reperfusion
      myocardial injury. We hypothesized that inducible ischemia leads to cytokine
      production, TF expression, and consequently persistent left ventricular
      dysfunction after dobutamine stress echocardiography (DSE) in coronary artery
      disease patients. METHODS AND RESULTS: DSE was performed in 103 patients with
      angiographically documented coronary artery disease. Blood samples were obtained
      at rest, at peak stress, and 30 minutes after cessation of dobutamine infusion
      for measurement of macrophage colony stimulating factor, IL-6, and TF. New or
      worsening wall motion abnormalities at peak stress and their duration into
      recovery were noted. Median IL-6 and TF levels were increased at peak stress and
      at 30 minutes into recovery compared with rest (2.7 and 2.4 versus 2.1 pg/mL for
      IL-6, 310 and 385 versus 266 pg/mL for TF [P<0.01] in patients with an ischemic
      response; n=55). Compared with rest, a greater release of IL-6 at peak stress and
      recovery was observed in patients with increasing number of ischemic segments at
      peak DSE (2 versus 3 to 4 versus 5 to 6 versus 7 to 8 segments; P=0.03). The time
      to recovery of wall motion abnormalities was also associated with IL-6 levels at
      peak stress and recovery (r=0.51 and r=0.39, P<0.05). Macrophage colony
      stimulating factor levels remained unchanged throughout DSE. CONCLUSIONS:
      Reversible ischemia induced during DSE increases IL-6 and TF plasma levels. IL-6
      is related to the extent of left ventricular dysfunction at peak stress and to
      persistent LV dysfunction during recovery.

PMID- 16286590
TI  - Total cavopulmonary connection flow with functional left pulmonary artery
      stenosis: angioplasty and fenestration in vitro.
AB  - BACKGROUND: In our multicenter study of the total cavopulmonary connection
      (TCPC), a cohort of patients with long-segment left pulmonary artery (LPA)
      stenosis was observed (35%). The clinically recognized detrimental effects of LPA
      stenosis motivated a computational fluid dynamic simulation study within 3
      dimensional patient-specific and idealized TCPC pathways. The goal of this study
      was to quantify and evaluate the hemodynamic impact of LPA stenosis and to judge
      interventional strategies aimed at treating it. METHODS AND RESULTS: Simulations
      were conducted at equal vascular lung resistance, modeling both discrete stenosis
      (DS) and diffuse long-segment hypoplasia with varying degrees of obstruction (0%
      to 80%). Models having fenestrations of 2 to 6 mm and atrium pressures of 4 to 14
      mm Hg were explored. A patient-specific, extracardiac TCPC with 85% DS was
      studied in its original configuration and after virtual surgery that dilated the
      LPA to 0% stenosis in the computer medium. Performance indices improved
      exponentially (R2>0.99) with decreasing obstruction. Diffuse long-segment
      hypoplasia was approximately 50% more severe with regard to lung perfusion and
      cardiac energy loss than DS. Virtual angioplasty performed on the 3-dimensional
      Fontan anatomy exhibiting an 85% DS stenosis produced a 61% increase in left lung
      perfusion and a 50% decrease in cardiac energy dissipation. After 4-mm
      fenestration, TCPC baffle pressure dropped by approximately 10% and left lung
      perfusion decreased by approximately 8% compared with the 80% DS case.
      CONCLUSIONS: DS <60% and diffuse long-segment hypoplasia <40% could be considered
      tolerable because both resulted in only a 12% decrease in left lung perfusion. In
      contrast to angioplasty, a fenestration (right-to-left shunt) reduced TCPC
      pressure at the cost of decreased left and right lung perfusion. These results
      suggest that pre-Fontan computational fluid dynamic simulation may be valuable
      for determining both the hemodynamic significance of LPA stenosis and the
      potential benefits of intervention.

PMID- 16286591
TI  - Oxidative stress by monoamine oxidase mediates receptor-independent cardiomyocyte
      apoptosis by serotonin and postischemic myocardial injury.
AB  - BACKGROUND: Serotonin (5-hydroxytryptamine [5-HT]), released by activated
      platelets during cardiac ischemia, is metabolized by the mitochondrial enzyme
      monoamine oxidase A (MAO-A). Because hydrogen peroxide is one of the byproducts
      of 5-HT degradation by MAO-A, we investigated the potential role of reactive
      oxygen species generated by MAOs in 5-HT-dependent cardiomyocyte death and post
      ischemia-reperfusion cardiac damage. METHODS AND RESULTS: Treatment of isolated
      adult rat cardiomyocytes with 5-HT induced intracellular oxidative stress and
      cell apoptosis. The apoptotic cascade triggered by 5-HT involves release of
      cytochrome c, upregulation of proapoptotic Bax protein, and downregulation of
      antiapoptotic Bcl-2 protein. These effects were prevented by inhibition of amine
      transporter or MAO, antioxidants, or iron chelation. In contrast, cardiomyocyte
      apoptosis was only slightly affected by the 5-HT(2B) receptor antagonist SB
      206553. In vivo, inhibition of MAO-A largely reduced myocardial ultrastructural
      damage induced by 30 minutes of ischemia followed by 60 minutes of reperfusion in
      the rat heart. Cardioprotective effects of MAO inhibitors were associated with
      the prevention of postischemic oxidative stress, neutrophil accumulation, and
      mitochondrial-dependent cell death and were not reverted by SB 206553.
      Administration of MAO-A inhibitors during ischemia was still effective in
      preventing cardiac damage. CONCLUSIONS: Our results supply the first direct
      evidence that oxidative stress induced by MAO is responsible for receptor
      independent apoptotic effects of 5-HT in cardiomyocytes and postischemic
      myocardial injury. These findings provide new insight into the mechanisms of 5-HT
      action in the heart and may constitute the basis for novel therapies.

PMID- 16286592
TI  - Fetal, developmental, and parental influences on childhood systolic blood
      pressure in 600 sib pairs: the Uppsala Family study.
AB  - BACKGROUND: Little is known about the contribution of maternal and paternal
      factors to the inverse association between birth weight and later blood pressure
      in human offspring. A study of within- and between-family associations of birth
      weight with blood pressure, which collected data on both parents, would address
      this gap in our knowledge. METHODS AND RESULTS: The study examined families
      composed of mother, father, and 2 full sibs delivered between 38 and 41 weeks'
      gestation within 36 months of each other. A total of 1967 families meeting our
      inclusion criteria were contacted and 602 were examined (children 5 to 14 years
      old, 1998 to 2000). Birth weight and gestational age were available from
      obstetric records. Systolic blood pressure in childhood was inversely associated
      with birth weight within families (-2.3 mm Hg/kg, 95% CI -4.4 to -0.3) after
      adjustment for gestational age, sex, height, and weight at examination. The
      between-family effect (-1.5 mm Hg/kg, -3.1 to 0.0) was strengthened on adjustment
      for maternal and paternal height and weight, whereas adjustment for paternal and
      maternal systolic blood pressure at examination independently attenuated the
      effect. CONCLUSIONS: The existence of an inverse association of birth weight with
      systolic blood pressure within families (adjusted for height and weight at
      examination) demonstrates that factors that vary between pregnancies in the same
      woman (including fetal genotype) can influence the later blood pressure of
      offspring. We conclude that this apparent fetal programming effect on blood
      pressure will not be eliminated solely by interventions aimed at modifying growth
      and cumulative nutritional status from conception through childhood or other
      fixed characteristics of future mothers.

PMID- 16286593
TI  - Cardiology patient page. Learn, take action, and live: a guide to using online
      tools to prevent and manage heart disease and stroke.

PMID- 16286594
TI  - Images in cardiovascular medicine. Multislice computed tomography for
      preinterventional mapping of complicated coronary artery injury.

PMID- 16286595
TI  - Images in cardiovascular medicine. Transient giant negative T waves associated
      with cardiac involvement of diffuse large B-cell lymphoma.

PMID- 16286596
TI  - Images in cardiovascular medicine. Systemic complications of infective
      endocarditis.

PMID- 16286597
TI  - Letter regarding article by Markus et al, "Dual antiplatelet therapy with
      clopidogrel and aspirin in symptomatic cardiac stenosis evaluated using doppler
      embolic signal detection: the Clopidogrel and Aspirin for Reduction of Emboli in
      Symptomatic Carotid Stenosis (CARESS) trial".

PMID- 16286598
TI  - Clinical trials in cardiovascular medicine in an era of marginal benefit, bias,
      and hyperbole.

PMID- 16286599
TI  - Insulin resistance, type 2 diabetes mellitus, and cardiovascular disease: the end
      of the beginning.

PMID- 16286600
TI  - Calling on reserves: granulocyte colony stimulating growth factor in cardiac
      repair.

PMID- 16286601
TI  - Cardiac troponins and renal failure: the evolution of a clinical test.

PMID- 16286602
TI  - Ambient air pollution is associated with increased risk of hospital cardiac
      readmissions of myocardial infarction survivors in five European cities.
AB  - BACKGROUND: Ambient air pollution has been associated with increases in acute
      morbidity and mortality. The objective of this study was to evaluate the short
      term effects of urban air pollution on cardiac hospital readmissions in survivors
      of myocardial infarction, a potentially susceptible subpopulation. METHODS AND
      RESULTS: In this European multicenter cohort study, 22,006 survivors of a first
      myocardial infarction were recruited in Augsburg, Germany; Barcelona, Spain;
      Helsinki, Finland; Rome, Italy; and Stockholm, Sweden, from 1992 to 2000.
      Hospital readmissions were recorded in 1992 to 2001. Ambient nitrogen dioxide,
      carbon monoxide, ozone, and mass of particles <10 microm (PM10) were measured.
      Particle number concentrations were estimated as a proxy for ultrafine particles.
      Short-term effects of air pollution on hospital readmissions for myocardial
      infarction, angina pectoris, and cardiac causes (myocardial infarction, angina
      pectoris, dysrhythmia, or heart failure) were studied in city-specific Poisson
      regression analyses with subsequent pooling. During follow-up, 6655 cardiac
      readmissions were observed. Cardiac readmissions increased in association with
      same-day concentrations of PM10 (rate ratio [RR] 1.021, 95% CI 1.004 to 1.039)
      per 10 microg/m3) and estimated particle number concentrations (RR 1.026 [95% CI
      1.005 to 1.048] per 10,000 particles/cm3). Effects of similar strength were
      observed for carbon monoxide (RR 1.014 [95% CI 1.001 to 1.026] per 200 microg/m3
      [0.172 ppm]), nitrogen dioxide (RR 1.032 [95% CI 1.013 to 1.051] per 8 microg/m3
      [4.16 ppb]), and ozone (RR 1.026 [95% CI 1.001 to 1.051] per 15 microg/m3 [7.5
      ppb]). Pooled effect estimates for angina pectoris and myocardial infarction
      readmissions were comparable. CONCLUSIONS: The results suggest that ambient air
      pollution is associated with increased risk of hospital cardiac readmissions of
      myocardial infarction survivors in 5 European cities.

PMID- 16286603
TI  - Which hemostatic markers add to the predictive value of conventional risk factors
      for coronary heart disease and ischemic stroke? The Caerphilly Study.
AB  - BACKGROUND: Few studies have examined whether hemostatic markers contribute to
      risk of coronary disease and ischemic stroke independently of conventional risk
      factors. This study examines 11 hemostatic markers that reflect different aspects
      of the coagulation process to determine which have prognostic value after
      accounting for conventional risk factors. METHODS AND RESULTS: A total of 2398
      men aged 49 to 65 years were examined in 1984 to 1988, and the majority gave a
      fasting blood sample for assay of lipids and hemostatic markers. Men were
      followed up for a median of 13 years, and cardiovascular disease (CVD) events
      were recorded. There were 486 CVD events in total, 353 with prospective coronary
      disease and 133 with prospective ischemic stroke. On univariable analysis,
      fibrinogen, low activated protein C ratio, D-dimer, tissue plasminogen activator
      (tPA), and plasminogen activator inhibitor-1 (PAI-1) were associated
      significantly with risk of CVD. On multivariable analyses with conventional risk
      factors forced into the proportional hazards model, fibrinogen, D-dimer, and PAI
      1 were significantly associated with risk of CVD, whereas factor VIIc showed an
      inverse association (P=0.001). In a model that contained the conventional risk
      factors, the hazard ratio for subsequent CVD in the top third of the distribution
      of predicted risk relative to the bottom third was 2.7 for subjects without
      preexisting CVD. This ratio increased to 3.7 for the model that also contained
      the 4 hemostatic factors. CONCLUSIONS: Fibrinogen, D-dimer, PAI-1 activity, and
      factor VIIc each has potential to increase the prediction of coronary
      disease/ischemic stroke in middle-aged men, in addition to conventional risk
      factors.

PMID- 16286604
TI  - Prognostic value of troponin T and I among asymptomatic patients with end-stage
      renal disease: a meta-analysis.
AB  - BACKGROUND: The prognostic usefulness of troponin enzymes in end-stage renal
      disease (ESRD) patients is controversial. To resolve this uncertainty of troponin
      as a prognostic tool, we conducted a systematic review to quantify the
      association between elevated troponin I or T and long-term total mortality among
      ESRD patients not suspected of having acute coronary syndrome. METHODS AND
      RESULTS: We conducted an unrestricted search from the MEDLINE, EMBASE, and DARE
      bibliographic databases to December 2004 using the terms troponin.mp. or exp
      troponin and exp kidney, exp renal, exp kidney disease exp renal replacement
      therapy. We also manually searched review articles and bibliographies to
      supplement the search. Studies were included if they were prospective
      observational studies, used cardiac-specific troponin assays, and evaluated long
      term risk of death or cardiac events for asymptomatic ESRD patients. Two authors
      independently abstracted data on study and patient characteristics. Studies
      findings were stratified according to troponin T or I levels. We used a random
      effects model to pool study results and tested for heterogeneity using chi2
      testing and used funnel-plot inspection to evaluate the presence of publication
      bias. Data from 28 studies (3931 patients) published between 1999 and December
      2004 were included in this review. Patients received dialysis for a median
      duration of 4 years, with a mean follow-up of 23 months. From the pooled
      analysis, elevated troponin T (>0.1 ng/mL) was significantly associated with
      increased all-cause mortality (relative risk, 2.64; 95% CI, 2.17 to 3.20).
      Although the prognostic effect sizes were all consistent with a positive
      relationship between troponin T and mortality, there was significant
      heterogeneity in the magnitude of these effect sizes (P=0.015). The funnel plot
      showed evidence of publication bias. Elevated troponin T was also strongly
      associated with increased cardiac death. Studies evaluating troponin I included a
      wide variety of assays and differing cut points, rendering synthesis of the study
      findings difficult. CONCLUSIONS: Elevated troponin T (>0.1 ng/mL) identifies a
      subgroup of ESRD patients who have poor survival and a high risk of cardiac death
      despite being asymptomatic. These findings suggest that troponin T is a promising
      risk stratification tool and may help frame therapeutic decisions. The clinical
      interpretation of elevated troponin I levels, however, remain unclear, largely
      because of the lack of standardization of assays.

PMID- 16286605
TI  - Supranormal myocardial creatine and phosphocreatine concentrations lead to
      cardiac hypertrophy and heart failure: insights from creatine transporter
      overexpressing transgenic mice.
AB  - BACKGROUND: Heart failure is associated with deranged cardiac energy metabolism,
      including reductions of creatine and phosphocreatine. Interventions that increase
      myocardial high-energy phosphate stores have been proposed as a strategy for
      treatment of heart failure. Previously, it has not been possible to increase
      myocardial creatine and phosphocreatine concentrations to supranormal levels
      because they are subject to tight regulation by the sarcolemmal creatine
      transporter (CrT). METHODS AND RESULTS: We therefore created 2 transgenic mouse
      lines overexpressing the myocardial creatine transporter (CrT-OE). Compared with
      wild-type (WT) littermate controls, total creatine (by high-performance liquid
      chromatography) was increased in CrT-OE hearts (66+/-6 nmol/mg protein in WT
      versus 133+/-52 nmol/mg protein in CrT-OE). Phosphocreatine levels (by 31P
      magnetic resonance spectroscopy) were also increased but to a lesser extent.
      Surprisingly, CrT-OE mice developed left ventricular (LV) dilatation (LV end
      diastolic volume: 21.5+/-4.3 microL in WT versus 33.1+/-9.6 microL in CrT-OE;
      P=0.002), substantial LV dysfunction (ejection fraction: 64+/-9% in WT versus
      49+/-13% in CrT-OE; range, 22% to 70%; P=0.003), and LV hypertrophy (by 3
      dimensional echocardiography and magnetic resonance imaging). Myocardial creatine
      content correlated closely with LV end-diastolic volume (r=0.51, P=0.02),
      ejection fraction (r=-0.74, P=0.0002), LV weight (r=0.59, P=0.006), LV end
      diastolic pressure (r=0.52, P=0.02), and dP/dt(max) (r=-0.69, P=0.0008). Despite
      increased creatine and phosphocreatine levels, CrT-OE hearts showed energetic
      impairment, with increased free ADP concentrations and reduced free-energy change
      levels. CONCLUSIONS: Overexpression of the CrT leads to supranormal levels of
      myocardial creatine and phosphocreatine, but the heart is incapable of keeping
      the augmented creatine pool adequately phosphorylated, resulting in increased
      free ADP levels, LV hypertrophy, and dysfunction. Our data demonstrate that a
      disturbance of the CrT-mediated tight regulation of cardiac energy metabolism has
      deleterious functional consequences. These findings caution against the
      uncritical use of creatine as a therapeutic agent in heart disease.

PMID- 16286606
TI  - New noninvasive method for assessment of left ventricular rotation: speckle
      tracking echocardiography.
AB  - BACKGROUND: Left ventricular (LV) torsion is due to oppositely directed apical
      and basal rotation and has been proposed as a sensitive marker of LV function. In
      the present study, we introduce and validate speckle tracking echocardiography
      (STE) as a method for assessment of LV rotation and torsion. METHODS AND RESULTS:
      Apical and basal rotation by STE was measured from short-axis images by automatic
      frame-to-frame tracking of gray-scale speckle patterns. Rotation was calculated
      as the average angular displacement of 9 regions relative to the center of a best
      fit circle through the same regions. As reference methods we used sonomicrometry
      in anesthetized dogs during baseline, dobutamine infusion, and apical ischemia,
      and magnetic resonance imaging (MRI) tagging in healthy humans. In dogs, the mean
      peak apical rotation was -3.7+/-1.2 degrees (+/-SD) and -4.1+/-1.2 degrees, and
      basal rotation was 1.9+/-1.5 degrees and 2.0+/-1.2 degrees by sonomicrometry and
      STE, respectively. Rotations by both methods increased (P<0.001) during
      dobutamine infusion. Apical rotation by both methods decreased during left
      anterior descending coronary artery occlusion (P<0.007), whereas basal rotation
      was unchanged. In healthy humans, apical rotation was -11.6+/-3.8 degrees and 
      10.9+/-3.3 degrees, and basal rotation was 4.8+/-1.7 degrees and 4.6+/-1.3
      degrees by MRI tagging and STE, respectively. Torsion measurement by STE showed
      good correlation and agreement with sonomicrometry (r=0.94, P<0.001) and MRI
      (r=0.85, P<0.001). CONCLUSIONS: The present study demonstrates that regional LV
      rotation and torsion can be measured accurately by STE, suggesting a new
      echocardiographic approach for quantification of LV systolic function.

PMID- 16286607
TI  - Low-density lipoprotein receptor genotype and response to pravastatin in children
      with familial hypercholesterolemia: substudy of an intima-media thickness trial.
AB  - BACKGROUND: The lipid-lowering effects of statin therapy show considerable
      interindividual variation in patients with familial hypercholesterolemia (FH).
      Whether the type of LDL receptor mutation predicts the response to statin
      treatment is not yet established. We analyzed the relationship between LDL
      receptor genotype and response to pravastatin treatment in children with FH using
      carotid intima-media thickness (IMT) to measure efficacy. METHODS AND RESULTS: In
      a randomized, placebo-controlled, double-blind, 2-year trial with pravastatin,
      193 children had genetically confirmed FH and were included in the present
      substudy. At baseline, children with null alleles had higher LDL cholesterol
      levels (difference, 0.94+/-0.19 mmol/L [SEM]; P<0.001) and a greater carotid IMT
      (difference, 0.019+/-0.01 mm; P=0.02) compared with children with receptor
      defective mutations. The decrease in carotid IMT during the trial was not
      significantly different in children with null alleles and receptor-defective
      mutations (0.018+/-0.012 and 0.012+/-0.010 mm; 2-way ANCOVA, P=0.7). After 2
      years of treatment, the children with null alleles continued to have greater
      carotid IMT than children with receptor-defective mutations (difference, 0.016+/
      0.01 mm; P=0.02). LDL cholesterol lowering tended to be less in carriers of null
      alleles compared with carriers of receptor-defective mutations (1.30+/-0.25 and
      1.85+/-0.20 mmol/L; 2-way ANCOVA, P=0.08). CONCLUSIONS: In FH children, we found
      that the null allele genotype was associated with a greater carotid IMT, higher
      LDL cholesterol levels, and a nonsignificant tendency to attenuated LDL
      cholesterol lowering compared with receptor-defective mutations. Null alleles
      identify FH patients at the highest cardiovascular disease risk who may benefit
      from more aggressive treatment started in childhood.

PMID- 16286608
TI  - Cell-based cardiac repair: reflections at the 10-year point.

PMID- 16286609
TI  - Managing abnormal blood lipids: a collaborative approach.
AB  - Current data and guidelines recommend treating abnormal blood lipids (ABL) to
      goal. This is a complex process and requires involvement from various healthcare
      professionals with a wide range of expertise. The model of a multidisciplinary
      case management approach for patients with ABL is well documented and described.
      This collaborative approach encompasses primary and secondary prevention across
      the lifespan, incorporates nutritional and exercise management as a significant
      component, defines the importance and indications for pharmacological therapy,
      and emphasizes the importance of adherence. Use of this collaborative approach
      for the treatment of ABL ultimately will improve cardiovascular and
      cerebrovascular morbidity and mortality.

PMID- 16286610
TI  - The Age-Related Eye Disease Study severity scale for age-related macular
      degeneration: AREDS Report No. 17.
AB  - OBJECTIVE: To develop a fundus photographic severity scale for age-related
      macular degeneration (AMD). METHODS: In the Age-Related Eye Disease Study,
      stereoscopic color fundus photographs were taken at baseline, at the 2-year
      follow-up visit, and annually thereafter. Photographs were graded for drusen
      characteristics (size, type, area), pigmentary abnormalities (increased pigment,
      depigmentation, geographic atrophy), and presence of abnormalities characteristic
      of neovascular AMD (retinal pigment epithelial detachment, serous or hemorrhagic
      sensory retinal detachment, subretinal or sub-retinal pigment epithelial
      hemorrhage, subretinal fibrous tissue). Advanced AMD was defined as presence of 1
      or more neovascular AMD abnormalities, photocoagulation for AMD, or geographic
      atrophy involving the center of the macula. We explored associations among right
      eyes of 3212 participants between severity of drusen characteristics and
      pigmentary abnormalities at baseline and development of advanced AMD within 5
      years of follow-up. RESULTS: A 9-step severity scale that combines a 6-step
      drusen area scale with a 5-step pigmentary abnormality scale was developed, on
      which the 5-year risk of advanced AMD increased progressively from less than 1%
      in step 1 to about 50% in step 9. Among the 334 eyes that had at least a 3-step
      progression on the scale between the baseline and 5-year visits, almost half
      showed stepwise progression through intervening severity levels at intervening
      visits. Replicate gradings showed agreement within 1 step on the scale in 87% of
      eyes. CONCLUSIONS: The scale provides convenient risk categories and has
      acceptable reproducibility. Progression along it may prove to be useful as a
      surrogate for progression to advanced AMD.

PMID- 16286611
TI  - Inflammatory markers in age-related maculopathy: cross-sectional analysis from
      the Muenster Aging and Retina Study.
AB  - OBJECTIVE: To evaluate recent reports indicating that plasma levels of fibrinogen
      and high-sensitivity C-reactive protein (CRP) are associated with age-related
      maculopathy (ARM). METHODS: From the baseline examinations of the Muenster Aging
      and Retina Study, a cohort of 1060 subjects aged 59 to 82 years was assembled. Of
      these, 873 persons (82%) with bilateral gradable fundus photographs and complete
      data on fibrinogen, CRP, and potential confounders were included in a cross
      sectional analysis. The main outcome measure was the association among
      fibrinogen, CRP, and ARM as assessed by multivariate logistic regression
      analysis. RESULTS: Fibrinogen and CRP levels were higher among participants with
      early and late ARM than among those without ARM. The crude odds ratios for ARM
      between the highest vs the lowest quartile were 1.90 (95% confidence interval
      [CI], 1.29-2.80) for fibrinogen and 1.43 (95% CI, 0.97-2.10) for CRP. After
      adjustment for cardiovascular risk factors, these odds ratios were 1.37 for
      fibrinogen (95% CI, 0.91-2.06) and 1.12 (95% CI, 0.73-1.73) for CRP. CONCLUSIONS:
      After adjustment for cardiovascular risk factors, we found no statistically
      significant association between fibrogen, CRP, and ARM. Therefore, our results do
      not indicate a role of systemic inflammation in ARM beyond what is already
      present owing to concurrent cardiovascular disease.

PMID- 16286612
TI  - Autofluorescence imaging of choroidal neovascularization due to age-related
      macular degeneration.
AB  - OBJECTIVE: To describe the autofluorescence (AF) characteristics of choroidal
      neovascularization (CNV) in patients with age-related macular degeneration.
      METHODS: Autofluorescence images of 65 consecutive eyes with CNV at various
      stages of evolution were analyzed. Twenty images were of recent-onset CNV (group
      1), 8 were of eyes 1 to 6 months after CNV diagnosis (group 2), and 37 were late
      stage CNV (group 3). Autofluorescence images from groups 1 and 2 were compared
      with fundus fluorescein angiographic images. RESULTS: Group 1 showed areas of
      hyperfluorescence on fundus fluorescein angiography corresponding to areas of
      normal AF in 16 of 20 cases, with adjacent areas of increased AF in 13 cases. The
      main areas of abnormal AF were larger than the main areas of abnormal
      fluorescence on fundus fluorescein angiography in 18 of the 20 cases. Groups 2
      and 3 showed areas of decreased AF corresponding to areas of previous leakage on
      fundus fluorescein angiography (in group 2) or atrophy. CONCLUSIONS: Preserved AF
      in group 1 indicates viable retinal pigment epithelium initially, which has
      implications for visual prognosis. Decreased AF in groups 2 and 3 indicates loss
      of retinal pigment epithelium and photoreceptors. Autofluorescence imaging may
      increase our understanding of CNV in age-related macular degeneration.

PMID- 16286613
TI  - Dynamic intraocular pressure measurements during vitrectomy.
AB  - OBJECTIVES: To directly measure dynamic intraocular pressure (IOP) during
      vitrectomy and to determine whether disposable pressure transducers placed in the
      infusion line can indirectly measure with accuracy the dynamic IOP during
      vitrectomy. METHODS: Experimental clinical study of 10 patients undergoing
      vitrectomy. Dynamic IOP was sampled via an extra pars plana incision with a
      catheter transducer equipped to measure direct IOP during vitrectomy by attaching
      a metal flange near the pressure-sensing tip. Disposable blood pressure
      transducers were placed in the infusion tubing fluid path to determine the IOP by
      indirect means. During various maneuvers of vitrectomy including air-fluid
      exchange and gas-forced infusion, pressure measurements were taken simultaneously
      from the indwelling pressure transducer and the disposable blood pressure sensors
      in the infusion line. RESULTS: The directly measured IOP varied between 0 and 120
      mm Hg during vitrectomy. During fluid flow, the indirectly measured IOP,
      calculated from the infusion line pressures, accurately corresponded with the
      directly measured IOP. CONCLUSIONS: Closed vitrectomy causes wide fluctuations in
      IOP. The IOP can be accurately measured during fluid flow with inline sensors.

PMID- 16286614
TI  - Long-term visual outcome following chemoreduction for retinoblastoma.
AB  - OBJECTIVE: To evaluate long-term visual outcome following chemoreduction. DESIGN:
      Interventional case series evaluating 54 eyes of 40 children with retinoblastoma
      successfully treated with chemoreduction, consisting of a combination of
      intravenous carboplatin, etoposide phosphate, and vincristine sulfate plus focal
      therapy without external beam radiotherapy or enucleation. All patients were
      followed up for at least 5 years. Patient and tumor data were analyzed for their
      effect on the main outcome measures (final visual acuities of 20/40 or better and
      of 20/200 or better) using univariate and multivariate regression models.
      Patients who failed chemoreduction were excluded. RESULTS: There were 4 eyes in
      Reese-Ellsworth group I, 7 in group II, 3 in group III, 15 in group IV, and 25 in
      group V. The mean distance from the posterior tumor margin to the optic disc was
      2 mm, and from the tumor margin to the foveola it was 3 mm. After a mean follow
      up of 68 months, 27 eyes (50%) had a final visual acuity of 20/40 or better, and
      36 eyes (67%) had final visual acuity of 20/200 or better. Of 33 eyes with
      macular tumor, only 8 (24%) had a final visual acuity of 20/40 or better, and 15
      (45%) had a final visual acuity of 20/200 or better. Of 21 eyes with extramacular
      tumor, 19 (90%) had a final visual acuity of 20/40 or better, and all (100%) had
      a final visual acuity of 20/200 or better. CONCLUSION: The clinical factors that
      predicted visual acuity of 20/40 or better were a tumor margin at least 3 mm from
      the foveola and optic disc and an absence of subretinal fluid.

PMID- 16286615
TI  - Clinical comparison of contour and applanation tonometry and their relationship
      to pachymetry.
AB  - OBJECTIVES: To compare intraocular pressure readings of recently introduced
      dynamic contour tonometry (DCT) with pneumatonometry (PTG) and Goldmann
      applanation tonometry (GAT) and to correlate central corneal thickness (CCT) with
      these readings. DESIGN: Prospective, cross-sectional observation and instrument
      validation study. We included 258 independent eyes with normal anterior segment
      examinations results, irrespective of glaucoma diagnosis or glaucoma suspect.
      After pachymetry, DCT, PTG, and GAT were performed in a randomized order.
      Intraocular pressures as measured by DCT, PTG, and GAT were compared with each
      other and with CCT. RESULTS: Eyes with thinner CCTs tended to yield lower
      intraocular pressure measurements by GAT. A significant correlation (Pearson
      product moment correlation, P<.001) between CCT and GAT was found with a
      regression of 0.25 mm Hg per 10 microm (R2 = 0.060). Variation of CCT had no
      significant effect on intraocular pressure measurements by PTG (P = .10; R2 =
      0.01) and DCT (P = .80; R2<0.01). A piecewise regression model showed that GAT
      readings are not linearly correlated with CCT. Comparison of the slopes below and
      above 535 microm showed the highest significance (P<.001). CONCLUSIONS: Goldmann
      applanation tonometry readings are potentially influenced by CCT, whereas PTG and
      DCT seem to be less dependent on CCT. Correlation between CCT and GAT is not
      linear. A simple correction formula suggesting a linear relationship might not be
      correct.

PMID- 16286616
TI  - Bimatoprost-induced periocular skin hyperpigmentation: histopathological study.
AB  - OBJECTIVE: To investigate light microscopic and ultrastructural changes in
      bimatoprost-induced skin hyperpigmentation. METHODS: Eyelid biopsy specimens from
      bimatoprost-treated patients and matched controls were examined by light
      microscopy and transmission electron microscopy. Using an image analyzer, melanin
      granules were counted on Fontana-Masson-stained sections, and melanosomes were
      counted on electron micrographs. Immunohistochemical analysis was performed with
      antibodies against S100 and CD3. Positively labeled cells were counted. RESULTS:
      By light microscopy, a marked increase in the number of melanin granules was
      noted in the bimatoprost-treated specimens. Electron microscopy demonstrated
      dermal melanocytes with prominent rough endoplasmic reticulum and abundant normal
      sized melanosomes in different stages of maturation as compared with control
      specimens. Furthermore, the keratinocytes of the bimatoprost-treated specimens
      showed abundant mature melanosomes when compared with controls. Also of note,
      atypical melanocytes were absent in both specimens. The S100-positive melanocytes
      were comparable in bimatoprost-treated and control specimens. Few CD3- and CD68
      positive cells in the bimatoprost-treated specimens were noted in both groups.
      CONCLUSION: Bimatoprost-induced periocular hyperpigmentation is caused by
      increased melanogenesis. There was no evidence of melanocyte proliferation or
      prostaglandin-induced inflammation in the specimens that were examined.

PMID- 16286617
TI  - Differences in visual function and optic nerve structure between healthy eyes of
      blacks and whites.
AB  - OBJECTIVE: To investigate differences in visual function, optic disc topography,
      and retinal nerve fiber layer (RNFL) thickness between healthy eyes of blacks and
      whites. METHODS: Visual function was assessed in healthy eyes of 50 blacks and 50
      whites using standard automated perimetry, short-wavelength automated perimetry,
      and frequency doubling technology perimetry. Optic disc topography and RNFL
      thickness were measured using the Heidelberg Retina Tomograph and the optical
      coherence tomograph. RESULTS: Mean standard automated perimetry mean deviations
      were within the normal range for both groups. Blacks had worse mean deviation
      values than whites using frequency doubling technology perimetry (mean +/- SD, 
      1.8 +/- 3.2 dB vs -0.1 +/- 2.4 dB), blacks had larger optic disc areas than
      whites using the Heidelberg Retina Tomograph (mean +/- SD, 2.1 +/- 0.4 mm2 vs 1.7
      +/- 0.4 mm2), the RNFL of blacks was thicker than that of whites by 16.91 microm
      superiorly and 10.10 microm inferiorly using optical coherence tomography, and
      blacks had slightly higher intraocular pressures than whites (mean +/- SD, 16.5
      +/- 2.5 mm Hg vs 15.2 +/- 3.2 mm Hg) and thinner central corneas (mean +/- SD,
      540.5 +/- 43.2 microm vs 560.9 +/- 35.5 microm). No racial differences were found
      in mean RNFL thickness, pattern standard deviation on all tests, or any of the
      short-wavelength automated perimetry variables. CONCLUSIONS: Minimal racial
      differences in visual function were found, but race significantly affected optic
      disc topography and superior and inferior RNFL thickness measurements in healthy
      eyes. The racial differences observed for intraocular pressure could
      theoretically increase after correcting for central corneal thickness.
      Prospective studies are needed to further investigate these findings.

PMID- 16286618
TI  - Visual field abnormalities in nonarteritic anterior ischemic optic neuropathy:
      their pattern and prevalence at initial examination.
AB  - OBJECTIVE: To evaluate the pattern of various types of visual field defects and
      their prevalence at initial examination of nonarteritic anterior ischemic optic
      neuropathy (NA-AION). METHODS: The data were compiled from 312 consecutive eyes
      (in 265 patients) that fulfilled our inclusion and exclusion criteria. A
      comprehensive ophthalmic evaluation was performed, including recording of visual
      acuity, visual fields with a Goldmann perimeter (using I-2e, I-4e, and V-4e
      targets regularly), and intraocular pressure; slitlamp examination of the
      anterior segment; ophthalmoscopy; color fundus photography; and in acute cases,
      fluorescein fundus angiography. The visual field defects were divided into 2
      groups: (1) general field defects and (2) various types of scotoma in the central
      30 degrees . The prevalence of various types of visual field defects was
      estimated for I-2e, I-4e, and V-4e isopters by dividing the total number of eyes
      with the defect by the total number of eyes that could see that particular
      target. Exact 95% confidence limits for the prevalence were computed. RESULTS: Of
      the 265 patients, 169 (63.7%) were male and the mean +/- SD patient age was 55.0
      +/- 9.1 years. The median interval between the first visual field test and the
      onset of NA-AION was 2 weeks. Of the 312 eyes, the I-2e target was seen by 75.3%,
      the I-4e target by 90.7%, and the V-4e target by 100%. Overall prevalence of
      general visual field defects was 83.4% with I-2e, 78.8% with I-4e, and 68.9% with
      V-4e, whereas the prevalence of scotoma(s) within the central 30 degrees was
      55.3%, 49.5%, and 36.2%, respectively. Central scotoma was seen in 48.5% with I
      2e, 43.8% with I-4e, and 29.2% with V-4e. A detailed prevalence of various types
      of visual field defects is given. Relative inferior altitudinal defect was most
      common (34.9% with I-2e and 22.3% with I-4e), but the absolute inferior
      altitudinal defect was seen in only 8.0%. By contrast, absolute inferior nasal
      sector visual loss was the most common defect detected in NA-AION (22.4%), but it
      occurred in only 3.4% with I-2e and 11.0% with I-4e. Overall, loss of the nasal
      part of the visual field was the most common occurrence. CONCLUSIONS: Our study
      demonstrated that NA-AION eyes may initially show a variety of optic nerve
      related visual field defects. Our study also showed that an absolute inferior
      nasal visual field defect is much more common (22.4%) than an absolute inferior
      altitudinal visual field defect (8.0%) in NA-AION and could be considered the
      most characteristic single field defect in NA-AION. We found that a combination
      of relative inferior altitudinal defect with absolute inferior nasal defect is
      usually the most common pattern in NA-AION.

PMID- 16286619
TI  - Electroretinographic effects of an intravitreal injection of triamcinolone in
      rabbit retina.
AB  - OBJECTIVE: To investigate the clinical, histologic, and electroretinographic
      effects of intravitreal injection of triamcinolone acetonide suspension in the
      rabbit retina. METHODS: Three groups of 6 rabbits each received intravitreal
      injections. Group 1 received 4 mg of triamcinolone acetonide, group 2 received an
      equal volume (0.1 mL) of the corticosteroid supernatant, and group 3 received 4
      mg of triamcinolone acetonide with the supernatant replaced with balanced salt
      solution. Uninjected left eyes served as controls. Electroretinograms were
      obtained at baseline and at 3 to 4 and 6 to 7 days after injection of
      triamcinolone. Enucleated eyes were examined histologically. RESULTS: Ocular
      examination revealed no differences among the 3 groups. When subjected to
      stimulation with moderate to high flash intensities, eyes that had received
      intravitreal injections of triamcinolone (groups 1 and 3) had a 10% to 25%
      increase in dark-adapted a- and b-wave electroretinographic amplitudes. No
      histologic differences were observed between injected and control eyes.
      CONCLUSIONS: Intravitreal injection of 4 mg of triamcinolone acetonide does not
      cause a toxic reaction in the rabbit retina after 7 days. Triamcinolone therapy
      may augment the rod-driven electroretinographic responses, suggesting a mechanism
      by which visual function may improve. Clinical Relevance Evaluation of the toxic
      effects of triamcinolone is useful because of increased applications of
      intravitreal injection.

PMID- 16286620
TI  - A simplified severity scale for age-related macular degeneration: AREDS Report
      No. 18.
AB  - OBJECTIVE: To develop a simplified clinical scale defining risk categories for
      development of advanced age-related macular degeneration (AMD). METHODS:
      Following development of a detailed scale for individual eyes based on gradings
      of fundus photographs in the Age-Related Eye Disease Study, rates of progression
      to advanced AMD were assessed in cross-tabulations of presence or absence in each
      eye of 2 easily identified retinal abnormalities, drusen and pigment
      abnormalities. Large drusen and any pigment changes were particularly predictive
      of developing advanced AMD. RESULTS: The scoring system developed for patients
      assigns to each eye 1 risk factor for the presence of 1 or more large (> or = 125
      microm, width of a large vein at disc margin) drusen and 1 risk factor for the
      presence of any pigment abnormality. Risk factors are summed across both eyes,
      yielding a 5-step scale (0-4) on which the approximate 5-year risk of developing
      advanced AMD in at least one eye increases in this easily remembered sequence: 0
      factors, 0.5%; 1 factor, 3%; 2 factors, 12%; 3 factors, 25%; and 4 factors, 50%.
      For persons with no large drusen, presence of intermediate drusen in both eyes is
      counted as 1 risk factor. CONCLUSION: This simplified scale provides convenient
      risk categories for development of advanced AMD that can be determined by
      clinical examination or by less demanding photographic procedures than used in
      the Age-Related Eye Disease Study.

PMID- 16286621
TI  - Prevalence of age-related macular degeneration in a population-based sample of
      Hispanic people in Arizona: Proyecto VER.
AB  - OBJECTIVE: To report the prevalence of age-related macular degeneration (AMD) in
      a population-based sample of Hispanic individuals aged 50 years and older.
      METHODS: Proyecto VER (Vision and Eye Research) is a population-based study of
      blindness and visual impairment of Hispanic people in Arizona. Participants
      underwent complete ophthalmic evaluation, including stereoscopic fundus
      photography of fields 1, 2, and 4. All photographs for participants aged 50 years
      and older were graded using the Wisconsin Age-Related Maculopathy Grading system.
      The following signs were graded: drusen size, drusen type, and the area covered
      by drusen; pigmentary abnormalities; geographic atrophy; and exudative AMD.
      RESULTS: Sixty-seven percent (3178) of the original 4774 participants were 50
      years of age or older. Of those, 92% (2928) had fundus photographs in at least 1
      eye, and 95% (2780) of the photographs were of sufficient quality to grade early
      and late AMD. OUTCOME MEASURES: The overall prevalence of late AMD was 0.5%. The
      prevalence increased from 0.1% in the 50- to 59-year age group to 4.3% in the
      group aged 80 years and older. Likewise, early AMD was strongly associated with
      age with a prevalence of 20% in the 50- to 59-year age group, increasing to 54%
      in the group aged 80 years and older. The prevalence of early AMD in Hispanic
      people was significantly higher than the reported prevalence in the white
      population. However, the prevalence of late AMD was lower than the estimates for
      the white population of the United States. CONCLUSIONS: Although early macular
      changes were very common among Hispanic people, the prevalence of late AMD was
      infrequent. Further work is necessary to understand the underlying reasons for
      the different patterns of presentation of early and late signs of AMD among
      racial/ethnic groups and to characterize early AMD based on predictive value for
      severe disease in different populations.

PMID- 16286622
TI  - Poor uptake of cataract surgery in nursing home residents: the Salisbury Eye
      Evaluation in Nursing Home Groups study.
AB  - OBJECTIVE: To compare the uptake of cataract surgery in nursing homes in which
      assistance was provided in obtaining services with that in control homes.
      METHODS: The Salisbury Eye Evaluation in Nursing Home Groups (SEEING) project is
      a randomized clinical trial studying the effect of a comprehensive vision
      restoration-rehabilitation program, including the provision of cataract surgery
      services when needed. Twenty-eight nursing homes in the Eastern Shore area of
      Maryland and Delaware were matched in pairs by size and payment type. Nursing
      homes within each pair were randomized to usual care or targeted intervention.
      Persons with cataract causing visual acuity in the better eye to be worse than
      20/40 were informed of the possible benefit of cataract surgery. For those in
      intervention homes, additional support was provided in obtaining cataract
      surgery. RESULTS: Of residents with vision-impairing cataract in intervention
      homes, 31% underwent cataract surgery vs 2% in usual-care facilities. Residents
      with cataract compared with all residents without visual impairment, regardless
      of nursing home assignment, tended to be older (mean age, 86.7 vs 82.1 years;
      P<.001), were more likely to be black (age-adjusted P<.001), had lower Mini
      Mental State Examination scores (mean, 11.7 vs 16.2; age-adjusted P<.001), and
      longer length of stay (mean, 42.3 vs 24.4 months; P<.001). Furthermore, cataract
      was associated with significant visual impairment and with functional
      limitations, with 20% of those recommended for surgery having a visual acuity of
      20/100 or worse in the better-seeing eye. CONCLUSIONS: Screening for and
      identifying cataracts as a cause of vision loss rarely results in uptake of
      cataract surgery services in nursing homes. The addition of a support system to
      facilitate the process of scheduling surgery and getting to and from the hospital
      dramatically increases uptake rates.

PMID- 16286623
TI  - Late development of vitelliform lesions and flecks in a patient with best
      disease: clinicopathologic correlation.
AB  - OBJECTIVE: To provide the clinicopathologic findings of a patient who developed
      the clinical characteristics of Best disease (typically considered a juvenile
      macular degeneration) at the age of 75 years after being documented to be
      ophthalmoscopically normal at the age of 51 years. DESIGN: A member of a large
      family with Best disease, possessing a Y227N mutation in the VMD2 gene (the gene
      responsible for the disease, which encodes the bestrophin protein), developed
      small vitelliform lesions in both eyes at the age of 75 years and later developed
      yellow flecklike depositions at the level of the retinal pigment epithelium
      (RPE), which were also identified in fundus photographs of family members. The
      patient died at the age of 93 years, and the histological features of the macular
      lesion and peripheral flecks were examined. RESULTS: Histopathologically, the
      retinal outer nuclear layer was attenuated, particularly in the macula. This
      attenuation was frequently associated with normal RPE. A large area of
      photoreceptor degeneration was present in the central macula, with loss of the
      underlying RPE cells. Outside of this region, the RPE density was within normal
      limits. The peripheral flecks were clusters of basal laminar deposits and drusen.
      Bestrophin immunohistochemistry revealed labeling along both the basolateral and
      apical membranes of the RPE. CONCLUSIONS: Findings characteristic of Best disease
      may not manifest in a molecularly affected individual until late in life.
      Mutations in bestrophin appear to lead to extracellular deposit formation outside
      the macula in some families. The distribution of bestrophin in the RPE suggests
      that the protein may be mistargeted in those with Best disease who have the Y227N
      mutation, and that this may be a cause of the associated RPE and photoreceptor
      dysfunction.

PMID- 16286624
TI  - Ultrasonic bone removal with the Sonopet Omni: a new instrument for orbital and
      lacrimal surgery.
AB  - We used a new instrument that ultrasonically removes bone (Sonopet Omni, model
      UST-2001 Ultrasonic Surgical Aspirator) in 13 orbital decompressions and 6
      dacryocystorhinostomies. We noted no surgical complications of ocular or soft
      tissue damage, infection, inflammation, or visual loss. Visualization,
      manipulation, ease of use, and speed were far superior with the Sonopet
      ultrasonic bone curette compared with drills or rongeurs. The Sonopet Omni is an
      outstanding innovation in technology for bone removal in surgery.

PMID- 16286625
TI  - Age-Related Eye Disease Study severity scale and simplified severity scale for
      age-related macular degeneration.

PMID- 16286626
TI  - Arnall Patz, MD: physician, scientist, and humanitarian: Director Emeritus, The
      Wilmer Eye Institute; recipient of the 2004 Presidential Medal of Freedom.

PMID- 16286628
TI  - Schisis in sickle cell retinopathy.

PMID- 16286627
TI  - Histopathological analysis of post-laser-assisted in situ keratomileusis corneal
      ectasia with intrastromal corneal ring segments.

PMID- 16286629
TI  - Periocular cutaneous pigmentary changes associated with bimatoprost use.

PMID- 16286630
TI  - Restoration of foveal anatomy and function following chemoreduction for bilateral
      advanced retinoblastoma with total retinal detachment.

PMID- 16286631
TI  - Idiopathic thrombocytopenic purpura with massive subretinal hemorrhage.

PMID- 16286632
TI  - Anterior orbital leiomyoma: possible pulley smooth muscle tissue tumor.

PMID- 16286633
TI  - Concern about the Pediatric Eye Disease Investigator Group 2-year follow-up
      study.

PMID- 16286635
TI  - Serpiginous choroiditis by any other name.

PMID- 16286634
TI  - Detection of retinal pigment epithelial changes by nonmydriatic fundus cameras.

PMID- 16286636
TI  - Power of partnering.

PMID- 16286637
TI  - Cell-free cloning using phi29 DNA polymerase.
AB  - We describe conditions for rolling-circle amplification (RCA) of individual DNA
      molecules 5-7 kb in size by >10(9)-fold, using phi29 DNA polymerase. The
      principal difficulty with amplification of small amounts of template by RCA using
      phi29 DNA polymerase is "background" DNA synthesis that usually occurs when
      template is omitted, or at low template concentrations. Reducing the reaction
      volume while keeping the amount of template fixed increases the template
      concentration, resulting in a suppression of background synthesis. Cell-free
      cloning of single circular molecules by using phi29 DNA polymerase was achieved
      by carrying out the amplification reactions in very small volumes, typically 600
      nl. This procedure allows cell-free cloning of individual synthetic DNA molecules
      that cannot be cloned in Escherichia coli, for example synthetic phage genomes
      carrying lethal mutations. It also allows cell-free cloning of genomic DNA
      isolated from bacteria. This DNA can be sequenced directly from the phi29 DNA
      polymerase reaction without further amplification. In contrast to PCR
      amplification, RCA using phi29 DNA polymerase does not produce mutant jackpots,
      and the high processivity of the enzyme eliminates stuttering at homopolymer
      tracts. Cell-free cloning has many potential applications to both natural and
      synthetic DNA. These include environmental DNA samples that have proven difficult
      to clone and synthetic genes encoding toxic products. The method may also speed
      genome sequencing by eliminating the need for biological cloning.

PMID- 16286638
TI  - Better than platinum? Fuel cells energized by enzymes.

PMID- 16286639
TI  - The beta 1a subunit is essential for the assembly of dihydropyridine-receptor
      arrays in skeletal muscle.
AB  - Homozygous zebrafish of the mutant relaxed (red(ts25)) are paralyzed and die
      within days after hatching. A significant reduction of intramembrane charge
      movements and the lack of depolarization-induced but not caffeine-induced Ca(2+)
      transients suggested a defect in the skeletal muscle dihydropyridine receptor
      (DHPR). Sequencing of DHPR cDNAs indicated that the alpha(1S) subunit is normal,
      whereas the beta(1a) subunit harbors a single point mutation resulting in a
      premature stop. Quantitative RT-PCR revealed that the mutated gene is
      transcribed, but Western blot analysis and immunocytochemistry demonstrated the
      complete loss of the beta(1a) protein in mutant muscle. Thus, the immotile
      zebrafish relaxed is a beta(1a)-null mutant. Interestingly, immunocytochemistry
      showed correct triad targeting of the alpha(1S) subunit in the absence of
      beta(1a). Freeze-fracture analysis of the DHPR clusters in relaxed myotubes
      revealed an approximately 2-fold reduction in cluster size with a normal density
      of DHPR particles within the clusters. Most importantly, DHPR particles in the
      junctional membranes of the immotile zebrafish mutant relaxed entirely lacked the
      normal arrangement in arrays of tetrads. Thus, our data indicate that the lack of
      the beta(1a) subunit does not prevent triad targeting of the DHPR alpha(1S)
      subunit but precludes the skeletal muscle-specific arrangement of DHPR particles
      opposite the ryanodine receptor (RyR1). This defect properly explains the
      complete deficiency of skeletal muscle excitation-contraction coupling in beta(1)
      null model organisms.

PMID- 16286640
TI  - T-bet-dependent expression of osteopontin contributes to T cell polarization.
AB  - The osteopontin (Opn) glycoprotein has been implicated in diverse physiological
      processes, including vascularization, bone formation, and inflammatory responses.
      Studies of its role in immune responses has suggested that Opn can set the early
      stage of type-1 immune (cell-mediated) responses through differential regulation
      of IL-12 and IL-10 cytokine gene expression in macrophages. Although Opn has been
      suggested to play a role in the development of type-1 immunity, little is known
      about control of Opn gene expression. Here, we report that Opn gene expression in
      activated T cells, but not macrophages, is regulated by T-bet, a transcription
      factor that controls CD4+ T helper (Th1) cell lineage commitment. We also find
      that T-bet-dependent expression of Opn in T cells is essential for efficient
      skewing of CD4+ T and CD8+ T cells toward the Th1 and type 1 CD8+ T cells (Tc1)
      pathway, respectively. Taken together, these findings begin to delineate the
      genetic basis of Opn expression in T cells and further clarify the role of Opn in
      Th and Tc1 development.

PMID- 16286642
TI  - An interpretation of size-scale plasticity in geometrically confined systems.
AB  - The mesoscopic constitutive behavior of face-centered cubic metals as a function
      of the system characteristic dimension recently has been investigated
      experimentally. Strong size effects have been identified in both polycrystalline
      submicron thin films and single crystal micro pillars. The size effect is
      manifested as an increase in strength and hardening rate as the system dimensions
      are decreased. In this article, we provide a mechanistic interpretation for the
      observed mesoscopic behavior. By performing 3D discrete dislocation dynamics
      simulations of grains representative of the system microstructure and associated
      characteristic dimensions, we show that the experimentally observed size effects
      can be qualitatively described. In these simulations, a constant density of
      dislocation sources per unit of grain boundary area is modeled by sources
      randomly distributed at grain boundaries. The source length (strength) is modeled
      by a Gaussian distribution, in which average and standard deviation is
      independent of the system characteristic dimension. The simulations reveal that
      two key concepts are at the root of the observed plasticity size effect. First,
      the onset of plasticity is governed by a dislocation nucleation-controlled
      process (sources of various length, i.e., strengths, in our model). Second, the
      hardening rate is controlled by source exhaustion, i.e., sources are active only
      once as a result of the limited dislocation mobility arising from size and
      boundary effects. The model postulated here improves our understanding of why
      "smaller is stronger" and provides predictive capabilities that should enhance
      the reliable design of devices in applications such as microelectronics and
      micro/nano-electro-mechanical systems.

PMID- 16286641
TI  - Decreased levels of CXC-chemokines in serum of benzene-exposed workers identified
      by array-based proteomics.
AB  - Benzene is an important industrial chemical and environmental contaminant that
      causes leukemia. To obtain mechanistic insight into benzene's mechanism of
      action, we examined the impact of benzene on the human serum proteome in a study
      of exposed healthy shoe-factory workers and unexposed controls. Two sequential
      studies were performed, each using sera from 10 workers exposed to benzene
      (overall mean benzene air level >30 ppm) and 10 controls. Serum samples were
      subjected to anion-exchange fractionation and bound to three types of ProteinChip
      arrays (Ciphergen Biosystems, Fremont, CA) [hydrophobic (H50), metal affinity
      (IMAC3-Cu), and cation exchange (WCX2)]. Protein-expression patterns were
      detected by surface-enhanced laser desorption/ionization (SELDI)-TOF MS. Three
      proteins (4.1, 7.7, and 9.3 kDa) were consistently down-regulated in exposed
      compared with control subjects in both studies. All proteins were highly
      inversely correlated with individual estimates of benzene exposure (r > 0.75).
      The 7.7- and 9.3-kDa proteins were subsequently identified as platelet factor
      (PF)4 and connective tissue activating peptide (CTAP)-III. Initial proteomic
      results for PF4 and CTAP-III were subsequently confirmed in a single experiment
      using a ProteinChip-array-based immunoassay(Ciphergen Biosystems). The altered
      expression of the platelet-derived CXC-chemokines (40% and 63% for PF4 and CTAP
      III, respectively) could not be explained by changes in absolute platelet counts.
      Thus, SELDI-TOF analysis of a limited number of exposed and unexposed subjects
      revealed that lowered expression of PF4 and CTAP-III proteins is a potential
      biomarker of benzene's early biologic effects and may play a role in the
      immunosuppressive effects of benzene.

PMID- 16286643
TI  - The asialoglycoprotein receptor clears glycoconjugates terminating with sialic
      acid alpha 2,6GalNAc.
AB  - Endogenous ligands have not, to date, been identified for the asialoglycoprotein
      receptor (ASGP-R), which is abundantly expressed by parenchymal cells in the
      liver of mammals. On the basis of the rapid clearance of BSA bearing multiple
      chemically coupled sialic acid (Sia)alpha2,6GalNAcbeta1,4GlcNAcbeta1,2Man
      tetrasaccharides (SiaGGnM-BSA) from the circulation, and the ability of the ASGP
      R hepatic lectin-1 subunit to bind SiaGGnM-BSA, we previously proposed that
      glycoproteins modified with structures terminating with Siaalpha2,6GalNAc may
      represent previously unrecognized examples of endogenous ligands for this
      receptor. Here, we have taken a genetic approach using wild-type and ASGP-R
      deficient mice to determine that the ASGP-R in vivo does indeed account for the
      rapid clearance of glycoconjugates terminating with Siaalpha2,6GalNAc. We have
      also determined that the ASGP-R is able to bind core-substituted oligosaccharides
      with the terminal sequence Siaalpha2,6Galbeta1,4GlcNAc but not those with the
      terminal Siaalpha2,3Galbeta1,4GlcNAc. We propose that glycoproteins bearing
      terminals Siaalpha2,6GalNAc and Siaalpha2,6Gal are endogenous ligands for the
      ASGP-R, and that the ASGP-R helps to regulate the relative concentration of serum
      glycoproteins bearing alpha2,6-linked Sia.

PMID- 16286644
TI  - Profile of Nancy A. Moran.

PMID- 16286647
TI  - Profile of William S. Knowles.

PMID- 16286645
TI  - Calcineurin regulates bone formation by the osteoblast.
AB  - Two of the most commonly used immunosuppressants, cyclosporine A and tacrolimus
      (FK506), inhibit the activity of a ubiquitously expressed Ca(2+)/calmodulin
      sensitive phosphatase, calcineurin. Because both drugs also cause profound bone
      loss in humans and in animal models, we explored whether calcineurin played a
      role in regulating skeletal remodeling. We found that osteoblasts contained mRNA
      and protein for all isoforms of calcineurin A and B. TAT-assisted transduction of
      fusion protein TAT-calcineurin Aalpha into osteoblasts resulted in the enhanced
      expression of the osteoblast differentiation markers Runx-2, alkaline
      phosphatase, bone sialoprotein, and osteocalcin. This expression was associated
      with a dramatic enhancement of bone formation in intact calvarial cultures.
      Calcineurin Aalpha(-/-) mice displayed severe osteoporosis, markedly reduced
      mineral apposition rates, and attenuated colony formation in 10-day ex vivo
      stromal cell cultures. The latter was associated with significant reductions in
      Runx2, bone sialoprotein, and osteocalcin expression, paralleled by similar
      decreases in response to FK506. Together, the gain- and loss-of-function
      experiments indicate that calcineurin regulates bone formation through an effect
      on osteoblast differentiation.

PMID- 16286646
TI  - CHR11, a chromatin-remodeling factor essential for nuclear proliferation during
      female gametogenesis in Arabidopsis thaliana.
AB  - Chromatin-remodeling factors regulate the establishment of transcriptional
      programs during plant development. Although 42 genes encoding members of the
      SWI2/SNF2 family have been identified in Arabidopsis thaliana, <10 have been
      assigned a precise function on the basis of a mutant phenotype, and none have
      been shown to play a specific role during the gametophytic phase of the plant
      life cycle. A. thaliana chromatin-remodeling protein 11 (CHR11) encodes an
      imitation of switch (ISWI)-like chromatin-remodeling protein abundantly expressed
      during female gametogenesis and embryogenesis in Arabidopsis. To determine the
      function of CHR11 in wild-type plants, we introduced a hairpin construct leading
      to the production of double-stranded RNA, which specifically degraded the
      endogenous CHR11 mRNA by RNA interference (RNAi). Transcription of the RNAi
      inducing hairpin RNA was driven by either a constitutive cauliflower mosaic virus
      35S promoter (CaMV35S) acting at most stages of the sporophytic phase or a newly
      identified specific promoter acting at the onset of the female gametophytic phase
      (pFM1). All adult transformants that constitutively lacked sporophytic CHR11
      activity showed reduced plant height and small cotyledonary embryos with limited
      cell expansion. In contrast, RNAi lines in which CHR11 was specifically silenced
      at the onset of female gametogenesis (megagametogenesis) had normal height and
      embryo size but had defective female gametophytes arrested before the completion
      of the mitotic haploid nuclear divisions. These results show that CHR11 is
      essential for haploid nuclear proliferation during megagametogenesis and cell
      expansion during the sporophytic phase, demonstrating the functional versatility
      of SWI2/SNF2 chromatin-remodeling factors during both generations of the plant
      life cycle.

PMID- 16286648
TI  - Evolutionary regulation of the blind subterranean mole rat, Spalax, revealed by
      genome-wide gene expression.
AB  - We applied genome-wide gene expression analysis to the evolutionary processes of
      adaptive speciation of the Israeli blind subterranean mole rats of the Spalax
      ehrenbergi superspecies. The four Israeli allospecies climatically and adaptively
      radiated into the cooler, mesic northern domain (N) and warmer, xeric southern
      domain (S). The kidney and brain mRNAs of two N and two S animals were examined
      through cross-species hybridizations with two types of Affymetrix arrays (mouse
      and rat) and muscle mRNA of six N and six S animals with spotted cDNA mouse
      arrays. The initial microarray analysis was hypothesis-free, i.e., conducted
      without reference to the origin of animals. Principal component analysis revealed
      that 20-30% of the expression signal variability could be explained by the
      differentiation of N-S species. Similar N-S effects were obtained for all tissues
      and types of arrays: two Affymetrix microarrays using probe oligomer signals and
      the spotted array. Likewise, ANOVA and t test statistics demonstrated significant
      N-S ecogeographic divergence and region-tissue specificity in gene expression.
      Analysis of differential gene expression between species corroborates previous
      results deduced by allozymes and DNA molecular polymorphisms. Functional
      categories show significant N-S ecologic putative adaptive divergent up
      regulation of genes highlighting a higher metabolism in N, and potential adaptive
      brain activity and kidney urine cycle pathways in S. The present results confirm
      ecologic-genomic separation of blind mole rats into N and S. Gene expression
      regulation appears to be central to the evolution of blind mole rats.

PMID- 16286649
TI  - Hzf protein regulates dendritic localization and BDNF-induced translation of type
      1 inositol 1,4,5-trisphosphate receptor mRNA.
AB  - The localization of certain mRNAs to dendrites and their local translation in
      synaptic regions are proposed to be involved in certain aspects of synaptic
      plasticity. A cis-acting element within the 3' untranslated region (3' UTR) of
      the targeted mRNAs, which is bound by a trans-acting RNA-binding protein,
      controls the dendritic mRNA localization. Here, we identified hematopoietic zinc
      finger (Hzf) as a trans-acting factor that regulates the dendritic mRNA
      localization of the type 1 inositol 1,4,5-trisphosphate receptor (IP(3)RI), a
      dendritically localized mRNA in cerebellar Purkinje cells, via binding to the 3'
      UTR. In Hzf-deficient mice, the dendritic localization of IP(3)RI mRNA and brain
      derived neurotrophic factor-induced IP(3)RI protein synthesis in the cerebellum
      were impaired. These findings suggest that Hzf is an RNA-binding protein that
      controls the dendritic mRNA localization and activity-dependent translation of
      IP(3)RI, and may be involved in some aspects of synaptic plasticity.

PMID- 16286650
TI  - The stress-regulated protein M6a is a key modulator for neurite outgrowth and
      filopodium/spine formation.
AB  - Neuronal remodeling is a fundamental process by which the brain responds to
      environmental influences, e.g., during stress. In the hippocampus, chronic stress
      causes retraction of dendrites in CA3 pyramidal neurons. We have recently
      identified the glycoprotein M6a as a stress-responsive gene in the hippocampal
      formation. This gene is down-regulated in the hippocampus of both socially and
      physically stressed animals, and this effect can be reversed by antidepressant
      treatment. In the present work, we analyzed the biological function of the M6a
      protein. Immunohistochemistry showed that the M6a protein is abundant in all
      hippocampal subregions, and subcellular analysis in primary hippocampal neurons
      revealed its presence in membrane protrusions (filopodia/spines). Transfection
      experiments revealed that M6a overexpression induces neurite formation and
      increases filopodia density in hippocampal neurons. M6a knockdown with small
      interference RNA methodology showed that M6a low-expressing neurons display
      decreased filopodia number and a lower density of synaptophysin clusters. Taken
      together, our findings indicate that M6a plays an important role in
      neurite/filopodium outgrowth and synapse formation. Therefore, reduced M6a
      expression might be responsible for the morphological alterations found in the
      hippocampus of chronically stressed animals. Potential mechanisms that might
      explain the biological effects of M6a are discussed.

PMID- 16286651
TI  - Reliable prediction of transcription factor binding sites by phylogenetic
      verification.
AB  - We present a statistical methodology that largely improves the accuracy in
      computational predictions of transcription factor (TF) binding sites in eukaryote
      genomes. This method models the cross-species conservation of binding sites
      without relying on accurate sequence alignment. It can be coupled with any motif
      finding algorithm that searches for overrepresented sequence motifs in individual
      species and can increase the accuracy of the coupled motif-finding algorithm.
      Because this method is capable of accurately detecting TF binding sites, it also
      enhances our ability to predict the cis-regulatory modules. We applied this
      method on the published chromatin immunoprecipitation (ChIP)-chip data in
      Saccharomyces cerevisiae and found that its sensitivity and specificity are 9%
      and 14% higher than those of two recent methods. We also recovered almost all of
      the previously verified TF binding sites and made predictions on the cis
      regulatory elements that govern the tight regulation of ribosomal protein genes
      in 13 eukaryote species (2 plants, 4 yeasts, 2 worms, 2 insects, and 3 mammals).
      These results give insights to the transcriptional regulation in eukaryotic
      organisms.

PMID- 16286652
TI  - Transthyretin constitutes a functional component in pancreatic beta-cell stimulus
      secretion coupling.
AB  - Transthyretin (TTR) is a transport protein for thyroxine and, in association with
      retinol-binding protein, for retinol, mainly existing as a tetramer in vivo. We
      now demonstrate that TTR tetramer has a positive role in pancreatic beta-cell
      stimulus-secretion coupling. TTR promoted glucose-induced increases in
      cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) and insulin release. This
      resulted from a direct effect on glucose-induced electrical activity and voltage
      gated Ca(2+) channels. TTR also protected against beta-cell apoptosis. The
      concentration of TTR tetramer was decreased, whereas that of a monomeric form was
      increased in sera from patients with type 1 diabetes. The monomer was without
      effect on glucose-induced insulin release and apoptosis. Thus, TTR tetramer
      constitutes a component in normal beta-cell function. Conversion of TTR tetramer
      to monomer may be involved in the development of beta-cell failure/destruction in
      type 1 diabetes.

PMID- 16286653
TI  - The ER aminopeptidase, ERAP1, trims precursors to lengths of MHC class I peptides
      by a "molecular ruler" mechanism.
AB  - Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an IFN-gamma-induced
      aminopeptidase in the endoplasmic reticulum that trims longer precursors to the
      antigenic peptides presented on MHC class I molecules. We recently reported that
      purified ERAP1 trimmed N-extended precursors but spared peptides of 8-9 residues,
      the length required for binding to MHC class I molecules. Here, we show another
      remarkable property of ERAP1: that it strongly prefers substrates 9-16 residues
      long, the lengths of peptides transported efficiently into the ER by the
      transporter associated with antigen processing (TAP) transporter. This
      aminopeptidase rapidly degraded a model 13-mer to a 9-mer and then stopped, even
      though the substrate and the product had identical N- and C-terminal sequences.
      No other aminopeptidase, including the closely related ER-aminopeptidase ERAP2,
      showed a similar length preference. Unlike other aminopeptidases, the activity of
      ERAP1 depended on the C-terminal residue of the substrate. ERAP1, like most MHC
      class I molecules, prefers peptides with hydrophobic C termini and shows low
      affinity for peptides with charged C termini. Thus, ERAP1 is specialized to
      process precursors transported by TAP to peptides that can serve as MHC class I
      epitopes. Its "molecular ruler" mechanism involves binding the hydrophobic C
      terminus of the substrate 9-16 residues away from the active site.

PMID- 16286654
TI  - Temperature-driven decoupling of key phases of organic matter degradation in
      marine sediments.
AB  - The long-term burial of organic carbon in sediments results in the net
      accumulation of oxygen in the atmosphere, thereby mediating the redox state of
      the Earth's biosphere and atmosphere. Sediment microbial activity plays a major
      role in determining whether particulate organic carbon is recycled or buried. A
      diverse consortium of microorganisms that hydrolyze, ferment, and terminally
      oxidize organic compounds mediates anaerobic organic matter mineralization in
      anoxic sediments. Variable temperature regulation of the sequential processes,
      leading from the breakdown of complex particulate organic carbon to the
      production and subsequent consumption of labile, low-molecular weight, dissolved
      intermediates, could play a key role in controlling rates of overall organic
      carbon mineralization. We examined sediment organic carbon cycling in a sediment
      slurry and in flow through bioreactor experiments. The data show a variable
      temperature response of the microbial functional groups mediating organic matter
      mineralization in anoxic marine sediments, resulting in the temperature-driven
      decoupling of the production and consumption of organic intermediates. This
      temperature-driven decoupling leads to the accumulation of labile, low-molecular
      weight, dissolved organic carbon at low temperatures and low-molecular weight
      dissolved organic carbon limitation of terminal metabolism at higher
      temperatures.

PMID- 16286655
TI  - Beneficial effects of concurrent autologous bone marrow cell therapy and
      metabolic intervention in ischemia-induced angiogenesis in the mouse hindlimb.
AB  - Lower-limb ischemia is a major health problem. Because of the absence of
      effective treatment in the advanced stages of the disease, amputation is
      undertaken to alleviate unbearable symptoms. Novel therapeutic approaches include
      the intramuscular use of autologous bone marrow cells (BMCs). Because tissue
      ischemia is associated with an overwhelming generation of oxygen radicals and
      negative effects due to perturbed shear-stress, metabolic intervention with
      antioxidants and l-arginine could potentially induce beneficial effects beyond
      those achieved by BMCs. The protective effect of autologous BMCs and vascular
      protection by metabolic cotreatment (1.0% vitamin E added to the chow and 0.05%
      vitamin C and 6% l-arginine added to the drinking water) were examined in
      ischemia-induced angiogenesis in the mouse hindlimb, a model of extensive acute
      peripheral arterial occlusion. i.v. BMC therapy improved blood flow and increased
      capillary densities and expression of Ki-67, a proliferation-associated protein.
      This beneficial effect was amplified by metabolic cotreatment, an intervention
      inducing vascular protection, at least in part, through the nitric oxide pathway,
      reduction of systemic oxidative stress, and macrophage activation. Therefore,
      although a cautious approach is mandatory when experimental findings are extended
      to human diseases, autologous BMCs together with metabolic intervention could be
      an effective clinical treatment for peripheral arterial disease.

PMID- 16286656
TI  - The role of opportunity in the unintentional introduction of nonnative ants.
AB  - A longstanding goal in the study of biological invasions is to predict why some
      species are successful invaders, whereas others are not. To understand this
      process, detailed information is required concerning the pool of species that
      have the opportunity to become established. Here we develop an extensive database
      of ant species unintentionally transported to the continental United States and
      use these data to test how opportunity and species-level ecological attributes
      affect the probability of establishment. This database includes an amount of
      information on failed introductions that may be unparalleled for any group of
      unintentionally introduced insects. We found a high diversity of species (232
      species from 394 records), 12% of which have become established in the
      continental United States. The probability of establishment increased with the
      number of times a species was transported (propagule pressure) but was also
      influenced by nesting habit. Ground nesting species were more likely to become
      established compared with arboreal species. These results highlight the value of
      developing similar databases for additional groups of organisms transported by
      humans to obtain quantitative data on the first stages of the invasion process:
      opportunity and transport.

PMID- 16286657
TI  - Chromatin domain activation via GATA-1 utilization of a small subset of dispersed
      GATA motifs within a broad chromosomal region.
AB  - Cis elements that mediate transcription factor binding are abundant within
      genomes, but the rules governing occupancy of such motifs in chromatin are not
      understood. The transcription factor GATA-1 that regulates red blood cell
      development binds with high affinity to GATA motifs, and initial studies suggest
      that these motifs are often unavailable for occupancy in chromatin. Whereas GATA
      2 regulates the differentiation of all blood cell lineages via GATA motif
      binding, the specificity of GATA-2 chromatin occupancy has not been studied. We
      found that conditionally active GATA-1 (ER-GATA-1) and GATA-2 occupy only a small
      subset of the conserved GATA motifs within the murine beta-globin locus. Kinetic
      analyses in GATA-1-null cells indicated that ER-GATA-1 preferentially occupied
      GATA motifs at the locus control region (LCR), in which chromatin accessibility
      is largely GATA-1-independent. Subsequently, ER-GATA-1 increased promoter
      accessibility and occupied the betamajor promoter. ER-GATA-1 increased erythroid
      Kruppel-like factor and SWI/SNF chromatin remodeling complex occupancy at
      restricted LCR sites. These studies revealed three phases of beta-globin locus
      activation: GATA-1-independent establishment of specific chromatin structure
      features, GATA-1-dependent LCR complex assembly, and GATA-1-dependent promoter
      complex assembly. The differential utilization of dispersed GATA motifs therefore
      establishes spatial/temporal regulation and underlies the multistep activation
      mechanism.

PMID- 16286658
TI  - Hypoxia inducible factor 1 alpha regulates T cell receptor signal transduction.
AB  - Low oxygen pressures exist in many solid tissues, including primary and secondary
      lymphoid organs. One key element in cellular adaptation to hypoxia is induced
      expression of hypoxia inducible factor (Hif) 1alpha. Here, we have examined the
      effect of Hif-1alpha, isolated from the myriad other effects of hypoxia, on T
      cell receptor (TCR) signaling in thymocytes. Because pVHL (von Hippel-Lindau
      protein) directs the proteolysis of Hif-1alpha under "normoxic" conditions, we
      achieved constitutive stabilization of Hif-1alpha through thymic deletion of Vhlh
      and reversed Hif-1alpha stabilization with double deletion of Vhlh and Hif
      1alpha. We found that constitutive activity of Hif-1alpha resulted in diminished
      Ca(2+) response upon TCR crosslinking despite equivalent activation of
      phospholipase C(gamma1), normal intracellular Ca(2+) stores, and normal entry of
      Ca(2+) across the plasma membrane. Altered Ca(2+) response was instead due to
      accelerated removal of Ca(2+) from the cytoplasm into intracellular compartments,
      which occurred in association with Hif-1alpha-dependent overexpression of the
      calcium pump SERCA2 (sarcoplasmic/endoplasmic reticulum calcium ATPase 2). These
      data suggest a unique mechanism for control of TCR signaling through Hif-1alpha,
      which may be operative at the physiologic oxygen tensions seen in solid lymphoid
      organs.

PMID- 16286659
TI  - Three small RNAs jointly ensure secondary metabolism and biocontrol in
      Pseudomonas fluorescens CHA0.
AB  - In many Gram-negative bacteria, the GacS/GacA two-component system positively
      controls the expression of extracellular products or storage compounds. In the
      plant-beneficial rhizosphere bacterium Pseudomonas fluorescens CHA0, the
      GacS/GacA system is essential for the production of antibiotic compounds and
      hence for biological control of root-pathogenic fungi. The small (119-nt) RNA
      RsmX discovered in this study, together with RsmY and RsmZ, forms a triad of GacA
      dependent small RNAs, which sequester the RNA-binding proteins RsmA and RsmE and
      thereby antagonize translational repression exerted by these proteins in strain
      CHA0. This small RNA triad was found to be both necessary and sufficient for
      posttranscriptional derepression of biocontrol factors and for protection of
      cucumber from Pythium ultimum. The same three small RNAs also positively
      regulated swarming motility and the synthesis of a quorum-sensing signal, which
      is unrelated to N-acyl-homoserine lactones, and which autoinduces the Gac/Rsm
      cascade. Expression of RsmX and RsmY increased in parallel throughout cell
      growth, whereas RsmZ was produced during the late growth phase. This differential
      expression is assumed to facilitate fine tuning of GacS/A-controlled cell
      population density-dependent regulation in P. fluorescens.

PMID- 16286662
TI  - Retention of the matricellular protein SPARC in the endoplasmic reticulum of
      chondrocytes from patients with pseudoachondroplasia.
AB  - Pseudoachondroplasia (PSACH) is an autosomal dominant disease characterized by
      dwarfism, morphological irregularities of long bones and hips, and early-onset
      osteoarthritis. This disease has been attributed to mutations in a structural
      protein of the cartilage extracellular matrix (ECM), cartilage oligomeric matrix
      protein (COMP), which result in its selective retention in the chondrocyte rough
      endoplasmic reticulum (ER). Accumulation of excessive amounts of mutated COMP
      might reflect a defect in protein trafficking by PSACH chondrocytes. Here we
      identify the matricellular protein SPARC as a component of this trafficking
      deficit. SPARC was localized to the hypertrophic chondrocytes in the normal human
      tibial growth plate and in cultured control cartilage nodules. In contrast,
      concentrated intracellular depots of SPARC were identified in nodules cultured
      from three PSACH patients with mutations in COMP. The accumulated SPARC was
      coincident with COMP and with protein disulfide isomerase, a resident chaperone
      of the rough ER, whereas SPARC and COMP were not coincident in the ECM of control
      or PSACH nodules. SPARC-null mice develop severe osteopenia and degenerative
      intervertebral disc disease, and exhibit attenuation of collagenous ECM. The
      retention of SPARC in the ER of chondrocytes producing mutant COMP indicates a
      new intracellular function for SPARC in the trafficking/secretion of cartilage
      ECM.

PMID- 16286660
TI  - Somatic integration of an oncogene-harboring Sleeping Beauty transposon models
      liver tumor development in the mouse.
AB  - The Sleeping Beauty (SB) transposon system can integrate foreign sequences of DNA
      in the genome of mouse somatic cells eliciting long-term expression in vivo. This
      technology holds great promise for human gene therapy as a nonviral technology to
      deliver therapeutic genes. SB also provides a means to study the effects of
      defined genetic elements, such as oncogenes, on somatic cells in mice. Here, we
      test the ability of the SB transposon system to facilitate somatic integration of
      a transposon containing an activated NRAS oncogene in mouse hepatocytes to elicit
      tumor formation. NRAS oncogene-driven tumors developed when such vectors were
      delivered to the livers of p19Arf-null or heterozygous mice. Delivery of the NRAS
      transposon cooperates with Arf loss to cause carcinomas of hepatocellular or
      biliary origin. These tumors allowed characterization of transposon integration
      and expression at the single-cell level, revealing robust NRAS expression and
      both transposase-mediated and random insertion of delivered vectors. Random
      integration and expression of the SB transposase plasmid was also observed in one
      instance. In addition, studies using effector loop mutants of activated NRAS
      provide evidence that mitogen-activated protein kinase activation alone cannot
      efficiently induce liver carcinomas. This system can be used to rapidly model
      tumors caused by defined genetic changes.

PMID- 16286661
TI  - Histone hyperacetylated domains across the Ifng gene region in natural killer
      cells and T cells.
AB  - Local histone acetylation of promoters precedes transcription of many genes.
      Extended histone hyperacetylation at great distances from coding regions of genes
      also occurs during active transcription of gene families or individual genes and
      may reflect developmental processes that mark genes destined for cell-specific
      transcription, nuclear signaling processes that are required for active
      transcription, or both. To distinguish between these, we compared long-range
      histone acetylation patterns across the Ifng gene region in natural killer (NK)
      cells and T cells that were or were not actively transcribing the Ifng gene. In T
      cells, long-range histone acetylation depended on stimulation that drives both T
      helper (Th) 1 differentiation and active transcription, and it depended
      completely or partially on the presence of Stat4 or T-bet, respectively, two
      transcription factors that are required for Th1 lineage commitment. In contrast,
      in the absence of stimulation and active transcription, similar histone
      hyperacetylated domains were found in NK cells. Additional proximal domains were
      hyperacetylated after stimulation of transcription. We hypothesize that formation
      of extended histone hyperacetylated domains across the Ifng gene region
      represents a developmental mechanism that marks this gene for cell- or stimulus
      specific transcription.

PMID- 16286663
TI  - Expression and effect of inhibition of aminopeptidase-A during nephrogenesis.
AB  - Aminopeptidase-A (APA) is a metalloprotease that cleaves N-terminal aspartyl and
      glutamyl residues from peptides. Its best-known substrate is angiotensin II (Ang
      II), the most active compound of the renin-angiotensin system (RAS). The RAS is
      involved in renal development. Most components of the RAS system are expressed in
      the developing kidney. Thus far, APA has not been studied in detail. In the
      present study we have evaluated the expression of APA at the protein, mRNA, and
      enzyme activity (EA) level in the kidney during nephrogenesis. Furthermore, we
      have studied the effect of inhibiting APA EA by injection of anti-APA antibodies
      into 1-day-old mice. APA expression was observed from the comma stage onwards,
      predominantly in the developing podocytes and brush borders of proximal tubular
      cells. Notably, APA was absent in the medulla or the renal arterioles. Inhibition
      of APA EA caused temporary podocyte foot-process effacement, suggesting a minimum
      role for APA during nephrogenesis.

PMID- 16286664
TI  - Human kallikrein 6 expression in salivary gland tumors.
AB  - Human kallikrein 6 (hK6), also known as zyme/protease M/neurosin), is expressed
      in many normal glandular tissues. The aim of this study was to determine whether
      hK6 is expressed in salivary gland tissues and salivary gland tumors (both benign
      and malignant), using an immunohistochemical method. Pleomorphic adenomas (PA),
      adenoid cystic carcinomas, polymorphous low-grade adenocarcinomas, acinic cell
      carcinomas, mucoepidermoid carcinomas, and adenocarcinomas not otherwise
      specified of both minor and major salivary glands were examined. Cells lining
      duct-like structures and non-duct-like cells were scored. Only in PA of minor
      salivary gland origin was overall staining higher in duct-like than in non-duct
      like cells. In all other tumors exhibiting both types of cells, hK6 staining was
      similar in both duct-like and non-duct-like cells. Tumors that exhibited non-duct
      like cells only also exhibited cytoplasmic staining. Results of this study show
      that salivary gland tumors express hK6, apparently downregulated in comparison
      with normal salivary gland tissue, and that this expression is not specific for
      any of the tumors studied.

PMID- 16286665
TI  - Naturally occurring anti-albumin antibodies are responsible for false positivity
      in diagnosis of autoimmune premature ovarian failure.
AB  - Autoimmunity is a well-established causative factor of premature ovarian failure
      (POF), and evidence for the same has been well reported in the literature.
      Detection of specific autoantibodies remains the most practical clinical research
      marker of any autoimmune disease. Variation in efficiency and specificity in the
      detection of ovarian autoantibodies has been reported. However, the frequency of
      false positivity and a solution to overcome this has not yet been reported.
      Herein, we report autoantibody to albumin as the likely responsible agent for
      false positivity. Our data indicate that presence of naturally existing
      autoalbumin antibodies in the circulation of normal women is responsible for the
      false signal seen in SDS-PAGE Western blot analysis and in immunohistochemistry
      (IHC). Having shown the presence of anti-albumin antibody in normal women as well
      as in the sera of POF patients, we have developed a novel blocking agent to
      overcome this problem. A high titer polyclonal antibody against human serum
      albumin was generated. This antibody showed immunoreactivity to albumin obtained
      from various sources. Preincubation of Western blots and IHC sections with this
      antibody drastically reduced background signals. The advantage of using this
      blocking was evident by identification of specific anti-ovarian antibodies in a
      group of POF patients. This blocking procedure made it possible to obtain a clear
      indication of the ovarian antibody status in women presenting with autoimmune
      POF.

PMID- 16286667
TI  - Improved recovery from prolonged exercise following the consumption of low
      glycemic index carbohydrate meals.
AB  - This study examined the effects of the glycemic index (GI) of post-exercise
      carbohydrate (CHO) intake on endurance capacity the following day. Nine active
      males participated in 2 trials. On day 1, subjects ran for 90 min at 70%
      VO(2max)(R1). Thereafter, they were supplied with either a high GI (HGI) or low
      GI (LGI) CHO diet which provided 8 g CHO/kg body mass (BM). On day 2, after an
      overnight fast, subjects ran to exhaustion at 70% VO(2max)(R2). Time to
      exhaustion during R2 was longer in the LGI trial (108.9 +/- 7.4 min) than in the
      HGI trial (96.9 +/- 4.8 min) (P < 0.05). Fat oxidation rates and free fatty acid
      concentrations were higher in the LGI trial than the HGI trial (P < 0.05). The
      results suggest that the increased endurance capacity was largely a consequence
      of the increased fat oxidation following the LGI recovery diet.

PMID- 16286666
TI  - Immunohistochemical localization of bone morphogenetic protein-signaling Smads
      during long-bone distraction osteogenesis.
AB  - In this study we investigated the expression of bone morphogenetic protein (BMP)
      signaling Smads in distraction osteogenesis (DO). Osteotomy of the right tibia
      was performed in 14 skeletally mature white New Zealand male rabbits. Lengthening
      was started 1 week later at a rate of 0.5 mm/12 hr and was maintained for 3
      weeks. Expression of Smad proteins 1, 4, 5, 6, 7, and 8 and Smad ubiquitin
      regulatory factors (Smurfs) 1 and 2 was evaluated in the distracted zone using
      immunohistochemistry. Expression of receptor-regulated Smads (R-Smads) 1, 5, and
      8 showed a significant increase during the distraction phase, followed by a
      gradual decrease during the consolidation phase. Smad 4 showed significant
      expression during both distraction and the beginning of the consolidation phase.
      Smad 6 and Smad 7 were highly expressed during the consolidation phase. Staining
      for both Smurfs 1 and 2 was maximal at the end of the distraction period.
      Staining for all proteins was most intense in chondrocyte and fibroblast-like
      cells. Expression pattern of R-Smads correlated with our previously reported
      expression pattern of BMPs 2, 4, and 7 and their receptors. These results
      therefore suggest a role for the whole BMP signaling pathway including the Smad
      proteins in DO.

PMID- 16286668
TI  - Reduction in muscle glycogen and protein utilization with glucose feeding during
      exercise.
AB  - Effects of feeding glucose on substrate metabolism during cycling were studied.
      Trained (60.0 +/- 1.9 mL x kg(-1) x min(-1)) males (N = 5) completed two 75 min,
      80% VO(2max) trials: 125 g 13(C)-glucose CHO); 13(C)-glucose tracer, 10 g (C).
      During warm-up (30 min 30% VO2max) 2 . 2 g 13(C)-glucose was given as bicarbonate
      pool primer. Breath samples and blood glucose were analyzed for 13(C/12)C with
      IRMS. Protein oxidation was estimated from urine and sweat urea. Indirect
      calorimetry (protein corrected) and 13(C/12)C enrichment in expired CO(2)and
      blood glucose allowed exogenous (Gexo), endogenous (Gendo), muscle (Gmuscle), and
      liver glucose oxidation calculations. During exercise (75 min) in CHO versus C
      (respectively): protein oxidation was lower (6.8 +/- 2.7, 18.8 +/- 5.9 g; P =
      0.01); Gendo was reduced (71.2 +/- 3.8, 80.7 +/- 5.7% P = 0.01); Gmuscle was
      reduced (55.3 +/- 6.1, 65.9 +/- 6.0%; P = 0.01) compensated by increased
      Gexo(58.3 +/- 2.1, 3.87 +/- 0.85 g; P = 0.000002). Glucose ingestion during
      exercise can spare endogenous protein and carbohydrate, in fed cyclists, without
      glycogen depletion.

PMID- 16286669
TI  - Effect of elk velvet antler supplementation on the hormonal response to acute and
      chronic exercise in male and female rowers.
AB  - To examine the effects of elk velvet antler supplementation (EVA) combined with
      training on resting and exercise-stimulated hormonal response, male (n = 25) and
      female (n = 21) rowers ingested either EVA (560 mg/d) or placebo (PL) during 10
      wk of training. VO(2max), 2000 m rowing time, leg and bench press strength were
      determined before and after 5 and 10 wk of training. Serum hormone levels were
      measured prior to and 5 and 60 min after a simulated 2000 m rowing race.
      VO(2max)and strength increased and 2000 m times decreased similarly (P < 0.05)
      with training. There was no significant difference between the EVA and PL group
      for any hormonal response. Testosterone (males only) and growth hormone (both
      genders) were higher 5 min after the simulated race (P < 0.05) but returned to
      baseline at 60 min. Cortisol was higher 5 and 60 min compared to rest (both
      genders) (P < 0.05) and was higher 60 min post-exercise following 5 and 10 wk of
      training. It appears that 10 wk of EVA supplementation does not significantly
      improve rowing performance nor alter hormonal responses at rest or after acute
      exercise than training alone.

PMID- 16286670
TI  - Effects of acute versus chronic L-carnitine L-tartrate supplementation on
      metabolic responses to steady state exercise in males and females.
AB  - Twelve healthy active subjects (6 male, 6 female) performed 60 min of exercise
      (60% VO(2max)) on 3 occasions after supplementing with L-Carnitine L-tartrate
      (LCLT) or placebo. Each subject received a chronic dose, an acute dose, and
      placebo in a randomized, double-blind crossover design. Dietary intake and
      exercise were replicated for 2 d prior to each trial. In males there was a
      significant difference in rate of carbohydrate (CHO) oxidation between placebo
      and chronic trials (P = 0.02) but not placebo and acute trials (P = 0.70), and
      total CHO oxidation was greater following chronic supplementation vs. placebo
      )mean +/- standard deviation) of 93.8 (17.3) g/hr and 78.2 (23.3) g/h,
      respectively). In females, no difference in rate of, or total, CHO oxidation was
      observed between trials. No effects on fat oxidation or hematological responses
      were noted in either gender group. Under these experimental conditions, chronic
      LCLT supplementation increased CHO oxidation in males during exercise but this
      was not observed in females.

PMID- 16286671
TI  - Astaxanthin supplementation does not attenuate muscle injury following eccentric
      exercise in resistance-trained men.
AB  - This investigation was designed to determine the effects of astaxanthin on
      markers of skeletal muscle injury. Twenty resistance trained men (mean +/-
      standard error of the mean : age , 25.1 +/- 1.6 y; height, 1.79 +/- 0.02 m;
      weight, 86.8 +/- 4.4 kg) were assigned to either a placebo (1732 mg safflower
      oil, n =10) or astaxanthin (BioAstin; 1732 mg safflower oil; haematococcus algae
      extract [contains 4 mg astaxanthin and 480 mg lutein]n = 10). Subjects consumed
      their assigned treatment for 3 wk prior to eccentric exercise (10 sets of 10
      repetitions at 85% of one repetition maximum) and through 96 h post-exercise.
      Muscle soreness, creatine kinase (CK), and muscle performance was measured before
      and through 96 h post-exercise. A similar response was observed for both
      treatment groups for all dependent variables, indicating that in resistance
      trained men, astaxanthin supplementation does not favorably affect indirect
      markers of skeletal muscle injury following eccentric loading.

PMID- 16286673
TI  - Lipidemic profile of athletes and non-athletes with similar body fat.
AB  - Although chronic exercise is generally believed to improve the lipidemic profile,
      it is not clear whether this is due to exercise training or to other determinants
      such as the usually low body fat of athletes. The aim of the present study was to
      compare the lipidemic profile of young lean athletes and non-athletes matched for
      percentage body fat. Fourteen endurance athletes and fourteen sedentary men
      participated in the study. Participants provided two blood samples at the
      beginning and end of a 7-d period, during which they recorded physical activity
      and food intake. Athletes had significantly higher energy expenditure and energy
      intake but not significantly different macronutrient composition of their diet
      from non-athletes. No significant differences were found in serum
      triacylglycerol, total cholesterol, high-density lipoprotein cholesterol and low
      density lipoprotein cholesterol concentrations between groups. These data suggest
      that athletes and non-athletes with similar body fat do not differ in their
      lipidemic profiles.

PMID- 16286672
TI  - Supplementation with beta-hydroxy-beta-methylbutyrate (HMB) and alpha
      ketoisocaproic acid (KIC) reduces signs and symptoms of exercise-induced muscle
      damage in man.
AB  - This study examined the effects of beta-hydroxyl-beta-methylbutyrate (HMB) and
      alpha-ketoisocaproic acid (KIC) supplementation on signs and symptoms of exercise
      induced muscle damage following a single bout of eccentrically biased resistance
      exercise. Six non-resistance trained male subjects performed an exercise protocol
      designed to induce muscle damage on two separate occasions, performed on the
      dominant or non-dominant arm in a counter-balanced crossover design. Subjects
      were assigned to an HMB/KIC (3 g HMB and 0.3 g alpha-ketoisocaproic acid, daily)
      or placebo treatment for 14 d prior to exercise in the counter-balanced crossover
      design. One repetition maximum (1RM), plasma creatine kinase activity (CK),
      delayed onset muscle soreness (DOMS), limb girth, and range of motion (ROM) were
      determined pre-exercise, at 1h, 24 h, 48 h, and 72 h post-exercise. DOMS and the
      percentage changes in 1RM, limb girth, and ROM all changed over the 72 h period
      (P < 0.05). HMB//IC supplementation attenuated the CK response, the percentage
      decrement in 1RM, and the percentage increase in limb girth (P < 0.05). In
      addition, DOMS was reduced at 24 h post-exercise (P < 0.05) in the HMB/KIC
      treatment. In conclusion, 14 d of HMB and KIC supplementation reduced signs and
      symptoms of exercise-induced muscle damage in non-resistance trained males
      following a single bout of eccentrically biased resistance exercise.

PMID- 16286674
TI  - Altered vitamin B12 status in recreational endurance athletes.
AB  - This study aimed to compare the vitamin B(12)and folate status of recreational
      endurance athletes and inactive controls by modern biomarkers. In 72 athletes (38
      +/- 7 y) and 46 inactive controls (38 +/- 9 y) serum levels of vitamin B(2),
      methylmalonic acid (MMA), holotranscobalamin II (holoTC), folate, and
      homocysteine (Hcy) were measured. Vitamin B(12)and folate levels of both groups
      were comparable, but athletes had higher median (25.-75. percentile) MMA [242
      (196 to 324) versus 175 (141 to 266) nmol/L] and holoTC concentrations [67 (52 to
      93) versus 55 (45 to 70) pmol/L] than controls. Hcy was slightly lower in
      athletes [9.2 (7.2 to 12.6) versus 10.8 (8.9 to 12.9) nmol/L]. In controls, we
      found the following correlations: vitamin B(12)and MMA (r = -0.38), vitamin
      B(12)and holoTC (r = 0.51), MMA and holoTC (r = -0.36). In athletes, MMA did not
      correlate with vitamin B(12)and holoTC. Our data suggests an altered vitamin
      B(12)metabolism in recreational athletes that needs further investigation.

PMID- 16286675
TI  - A comparison of pre-competition eating patterns in a group of non-elite
      triathletes.
AB  - A qualitative research study investigated food choice by triathletes prior to
      training and competition, and gauged attitudes towards nutritional management.
      Five focus groups were conducted with 7 male and 6 female non-elite triathletes.
      Sessions were semi-structured, tape recorded, and transcribed verbatim for coding
      and analysis. Transcripts were coded using grounded theory and higher order
      themes emerged including: "somatic complaints," "performance," "trust,"
      "preferences," and "routine." Food choices, especially those of the more
      competitive triathletes, were made to maximize performance. Choices were based on
      past experience and "trial and error" rather than specialist advice. Subjects
      varied in nutritional knowledge, which appeared to relate to the level of
      competitiveness. More competitive triathletes were interested in improving
      performance but distrusted others making their nutritional choices. Less
      competitive triathletes embraced nutritional manipulation for gains in cognitive
      and athletic performance. "Trust" became a focus of the study and warrants
      further investigation, as this is a crucial component of providing nutritional
      advice to competitive athletes and to the general population.

PMID- 16286676
TI  - Effect of the period of resting in elite judo athletes: hematological indices and
      copper/ zinc-dependent antioxidant capacity.
AB  - The purpose of this study was to evaluate the effect of the resting period on
      hematological and copper-zinc-dependent antioxidant indices in Brazilian elite
      judo athletes (n = 7). Venous blood samples were collected after 24-h and 5-d
      periods of resting following a competition, with an interval of 30 d between
      collections. Two months prior to and during the study, each athlete received an
      individualized adequate diet. Body composition was determined at both study
      periods. The following were analyzed: in whole blood, hemoglobin, hematocrit, red
      cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean
      corpuscular hemoglobin concentration, red cell distribution width, and white cell
      count; in plasma, zinc, copper, iron, ceruloplasmin, and total iron-binding
      capacity; in erythrocytes, metallothionein, copper/zinc superoxide dismutase, and
      osmotic fragility. Dietary intake and body composition did not affect the
      biochemical measurements. A significant reduction in ceruloplasmin and superoxide
      dismutase activity was found after 5 d compared to 24 h of resting. A significant
      correlation between erythrocyte metallothionein and red cell distribution width
      was observed after 24 h of resting (r = -0.83, p = 0.02), whereas positive
      correlations of metallothionein with hemoglobin, red cell count, and mean
      corpuscular hemoglobin concentration were observed after 5 d of resting (r >/=
      0.76, p </= 0.05). Our results suggest that a longer resting period favors
      homeostatic adjustments in the erythrocyte population and in the copper/zinc
      dependent antioxidant system in elite judo athletes.

PMID- 16286677
TI  - Selenoprotein P analysis in human plasma: a discrepancy between HPLC
      fractionation of human plasma with heparin-affinity chromatography and SDS-PAGE
      with immunoblot analysis.
AB  - Several recent analytical methods for determination of Se and selenoprotein P
      have involved high-performance liquid chromatography (HPLC) using heparin
      affinity columns coupled to inductively coupled plasma-mass spectrometry (ICP-MS)
      for Se detection. HPLC-ICP-MS chromatography using tandem HPLC columns with ICP
      MS detection was used to detect the major selenium-containing proteins in plasma
      (glutathione peroxidase, albumin, and selenoprotein P). The efficiency of HPLC
      separation of plasma selenoprotein P was investigated by analyzing HPLC fractions
      using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with
      immunoblot analysis. The HPLC fraction corresponding to selenoprotein P contained
      25.1% of total selenoprotein P as measured by immunoblot analysis. The majority
      (74.9%) of total selenoprotein P found by immunoblot analysis was contained in
      the early HPLC fractions, consistent with either poor heparin affinity, which was
      not evident based on the HPLC-ICP-MS technique alone or nonspecific binding of
      the antibody. Immunoblot analysis of selenoprotein relies on antibodies binding
      to a selenoprotein P epitope, which might be preserved when selenoprotein P is
      broken down to release selenocysteine residues. Immunoblot methods overestimate
      selenoprotein P and are not suitable for determinations of intact selenoprotein
      P.

PMID- 16286678
TI  - The in vitro uptake of glutamate in GLAST and GLT-1 transfected mutant CHO-K1
      cells is inhibited by manganese.
AB  - In the central nervous system (CNS), extracellular concentrations of amino acids
      (e.g., aspartate, glutamate) and divalent metals (e.g., zinc, copper, manganese)
      are primarily regulated by astrocytes. Adequate glutamate homeostasis and control
      over extracellular concentrations of these excitotoxic amino acids are essential
      for the normal functioning of the brain. Not only is glutamate of central
      importance for nitrogen metabolism but, along with aspartate, it is the primary
      mediator of excitatory pathways in the brain. Similarly, the maintenance of
      proper Mn levels is important for normal brain function. Brain glutamate is
      removed from the extracellular fluid mainly by astrocytes via high affinity
      astroglial Na+-dependent excitatory amino acid transporters, glutamate/aspartate
      transporter (GLAST) and glutamate transporter-1 (GLT-1). The effects of Mn on
      specific glutamate transporters have yet to be determined. As a first step in
      this process, we examined the effects of Mn on the transport of [D-2, 3-3H]D
      aspartate, a non-metabolizable glutamate analog, in Chinese hamster ovary cells
      (CHO) transfected with two glutamate transporter subtypes, GLAST (EAAT1) or GLT-1
      (EAAT2). Mn-mediated inhibition of glutamate transport in the CHO-K1 cell line
      DdB7 was pronounced in both the GLT-1 and GLAST transfected cells. This resulted
      in a statistically significant inhibition (p<0.05) of glutamate uptake compared
      with transfected control in the absence of Mn treatment. These studies suggest
      that Mn accumulation in the CNS might contribute to dysregulation of glutamate
      homeostasis.

PMID- 16286680
TI  - Serum mineral levels at pregnancy and postpartum in single and twin pregnant
      sheep.
AB  - This study was performed to investigate calcium (Ca), inorganic phosphorus (P),
      potassium (K), magnesium (Mg), and chlorine (Cl) levels in blood serum at d 60,
      100, and 150 of gestation and at d 45 after parturition and to find out the
      significance of differences for macromineral levels during these stages of single
      or twin gestation in Akkaraman sheep. Blood samples of 30 apparently healthy
      pregnant Akkaraman sheep (15 single pregnancies, 15 twin pregnancies) were used.
      The samples were analyzed using a biochemical analyzer for Ca, P, Na, K, and Mg
      concentrations and using the Schales method for Cl levels. A statistically
      significant decrease (p < 0.001 and p < 0.05) was found on d 100 of pregnancy for
      Ca levels and for serum inorganic P levels in both groups. Twin pregnant sheep
      were found to have lower (p < 0.05) serum Ca and inorganic P levels than sheep
      pregnant with one fetus on d 100 and 150. Significant decreases (p > 0.05, p <
      0.01) for serum Mg levels in both groups were recorded on d 100 and 150 of
      pregnancy. There were significant increases (p < 0.01) in serum Cl levels on d
      100 in single and twin pregnant sheep.

PMID- 16286679
TI  - Methylmercury alters the in vitro uptake of glutamate in GLAST- and GLT-1
      transfected mutant CHO-K1 cells.
AB  - In order to maintain normal functioning of the brain, glutamate homeostasis and
      extracellular levels of excitotoxic amino acids (EAA) must be tightly controlled.
      This is accomplished, in large measure, by the astroglial high-affinity Na+
      dependent EAA transporters glutamate/ aspartate transporter (GLAST) and glutamate
      transporter-1 (GLT-1). Methylmercury (MeHg) is a potent neurotoxicant. Astrocytes
      are known targets for MeHg toxicity, representing a site for mercury
      localization. MeHg is known to cause astrocytic swelling, EAA release, and uptake
      inhibition in astrocytes, leading to increased extracellular glutamate levels and
      ensuing neuronal excitotoxicity and degeneration. However, the mechanisms and
      contribution of specific glutamate transporters to MeHg-induced glutamate
      dyshomeostasis remain unknown. Accordingly, the present study was carried out to
      investigate the effects of MeHg on the transport of [d-2, 3-3H]-d-aspartate, a
      nonmetabolizable glutamate analog in Chinese hamster ovary cells (CHO)
      transfected with the glutamate transporter subtypes GLAST or GLT-1. Additional
      studies examined the effects of MeHg on mRNA and protein levels of these
      transporters. Our results indicate the following (1) MeHg selectively affects
      glutamate transporter mRNA expression. MeHg treatment (6 h) led to no discernible
      changes in GLAST mRNA expression; however, GLT-1 mRNA expression significantly (p
      < 0.001) increased following treatments with 5 or 10 microM MeHg. (2) Selective
      changes in the expression of glutamate transporter protein levels were also
      noted. GLAST transporter protein levels significantly (p < 0.001, both at 5 and
      10 microM MeHg) increased and GLT-1 transporter protein levels significantly (p <
      0.001) decreased following MeHg exposure (5 microM). (3) MeHg exposure led to
      significant inhibition (p < 0.05) of glutamate uptake by GLAST (both 5 and 10
      microM MeHg), whereas GLT-1 transporter activity was significantly (p < 0.01)
      increased following exposure to 5 and 10 microM MeHg. These studies suggest that
      MeHg contributes to the dysregulation of glutamate homeostasis and that its
      effects are distinct for GLAST and GLT-1.

PMID- 16286681
TI  - Effect of protein deficiency on macroelement and trace element levels of weanling
      rats' small intestine and liver tissues.
AB  - Protein energy malnutrition has become a major health issue in developing
      countries. In the present study, the effect of protein deficiency on the small
      intestine and liver tissue content of macroelements and trace elements was
      investigated in weanling rats. Forty-five male weanling Wistar albino rats were
      divided into three groups. The control group (C) was fed a standard diet
      containing 25% casein, whereas the two experimental groups E1 and E2 consumed 12%
      and 3% casein, respectively, over a period of 45 d. The tissue samples were
      analyzed for zinc, copper, iron, manganese, calcium, and magnesium by atomic
      absorption spectroscopy. The protein-deficient groups showed increased levels of
      iron in both tissues and decreased manganese in small intestine tissue from the
      E1 group. No other differences were found for the other elements. These results
      suggest that protein deficiency might cause iron accumulation in the liver and
      intestine and decreases of manganese in the small intestine.

PMID- 16286682
TI  - Evolution of liver antioxidant status and iron implication during the development
      of deoxycorticosterone-saline hypertension in rats.
AB  - Hypertension is known to be associated with an oxidative stress resulting from an
      imbalance of antioxidant defense mechanisms in various tissues. The purpose of
      this study was to investigate the relationship between the increase of arterial
      blood pressure, measured during the gradual development of experimental
      hypertension in deoxycorticosterone (DOCA)-salt-treated rats, and an early
      imbalance of liver antioxidant status. The levels of liver oxidant/antioxidant
      markers and iron were studied during the induction of hypertension in 3-, 6-, and
      8-wk DOCA-salt-treated Sprague-Dawley rats. Hepatic antioxidant defenses were
      decreased as early as 3 wk of hypertensive treatment: the decrease of peroxidase
      reductase-transferase and catalase activities was associated with a significant
      increase of thiobarbituric acid reactive substances (TBARS) levels. Liver
      oxidative stress increased until 6 wk and remained stable at 8 wk of DOCA-salt
      treatment. Concurrently, liver iron levels were increased at 6 wk and returned to
      normal values after 8 wk of hypertensive treatment. Iron seems to be an inductor
      of liver oxidative stress and responsible for the persistent oxidative stress,
      most likely through secondary free-radical release. Thus, our data (1) confirm
      that hypertension in DOCA-salt-treated rats might be a free-radical-dependent
      disease where hepatic oxidant/antioxidant imbalance is obviously involved from
      the beginning of blood pressure elevation and (2) suggest that the use of
      suitable iron chelators might reverse liver oxidative stress associated with the
      increase of blood pressure.

PMID- 16286684
TI  - Zinc deficiency decreases plasma erythropoietin concentration in rats.
AB  - In 1985, Paterson and Bettger found hypoplastic hematopoiesis in severely zinc
      deficient rats. Therefore, we investigated plasma erythropoietin concentration in
      zinc-deficient rats. Forty 4-wk-old male Sprague- Dawley rats were assigned into
      4 dietary treatment groups of 10 for the 4-wk study: zinc-deficient group (4.5 mg
      zinc and 35 mg iron/kg; -Zn), iron-deficient group (30 mg zinc/kg, no
      supplemental iron; -Fe), zinc/ iron-deficient group (4.5 mg zinc/kg, no
      supplemental iron; -Zn-Fe), and control group (AIN-93G; Cont). Water intake
      determined at d 19 was similar among all treatment groups. At d 27-28,
      bioimpedance was measured. The intracellular water/extracellular water ratio was
      significantly increased in the -Zn group (p < 0.05). Compared to the Cont, group,
      the plasma erythropoietin concentration was increased by iron deficiency and
      decreased by zinc deficiency (p < 0.01). Hematocrit was significantly decreased
      in both the -Fe and -Zn-Fe groups and was significantly increased in the -Zn
      group (p < 0.01). Transferrin saturation in the -Fe and -Zn-Fe groups was
      significantly lower than the Cont group (p < 0.01), and that of the -Zn group was
      highest among all groups. The low plasma erythropoietin concentration might
      account for depressed hematopoiesis associated with zinc deficiency.

PMID- 16286683
TI  - Effect of black cumin (Nigella sativa) on cadmium-induced oxidative stress in the
      blood of rats.
AB  - The protective effect of black cumin (Nigella sativa = NS) on cadmium-induced
      oxidative stress was studied in rats. The rats were randomly divided into three
      experimental groups: A (conrol), B (Cd treated), and C (Cd + NS treated), each
      containing 10 animals. The Cd-treated and Cd + NS-treated groups were injected
      subcutaneously daily with CdCl2 dissolved in isotonic NaCl in the amount of 2
      mL/kg for 30 d, resulting in a dosage of 0.49 mg Cd/kg/d. The control group was
      injected with only isotonic NaCl (2 mL/kg/d) throughout the experiment (for 30
      d). Three days prior to induction of CdCl2, the Cd + NS-treated group received a
      daily intraperitoneal injection of 0.2 mL/kg NS until the end of the study. Cd
      treatment increased significantly the malondialdehyde levels in plasma and
      erythrocyte (p<0.01 and p<0.05, respectively) and also increased significantly
      the antioxidant levels (superoxide dismutase, glutathione peroxidase, and
      catalase) (p<0.05) compared to the control group. Cd + NS treatment decreased
      significantly the elevated malondialdehyde levels in plasma and erythrocyte
      (p<0.01 and p<0.05, respectively) and also reduced significantly the enhanced
      antioxidant levels (p<0.05). Cd treatment increased significantly the activity of
      iron levels (p<0.05) in the plasma compared to the control group. Cd + NS
      treatment decreased the activity of iron levels (p<0.05) in the plasma compared
      to the Cd-treated group. In the control group with no treatment, histology of
      erythrocytes was normal. In the Cd-treated group, there were remarkable membrane
      destruction and hemolytic changes in erythrocytes. In the Cd + NS-treated group,
      these changes were less than in the Cd-treated group. Our results show that N.
      sativa exerts a protective effect against cadmium toxicity.

PMID- 16286686
TI  - Cancer risk among nuclear workers.

PMID- 16286685
TI  - Merger of the UK National Radiological Protection Board with the Health
      Protection Agency.

PMID- 16286687
TI  - Childhood cancer mortality in relation to the St Lucie nuclear power station.
AB  - An unusual county-wide excess of childhood cancers of brain and other nervous
      tissue in the late 1990s in St Lucie County, Florida, prompted the Florida
      Department of Health to conduct a case-control study within the county assessing
      residential chemical exposures. No clear associations were found, but claims were
      then made that the release of radioactive substances such as strontium 90 from
      the St Lucie nuclear power station, which began operating in 1976, might have
      played a role. To test the plausibility of this hypothesis, we extended by 17
      years a previous study of county mortality conducted by the National Cancer
      Institute. Rates of total cancer, leukaemia and cancer of brain and other nervous
      tissue in children and across all ages in St Lucie County were evaluated with
      respect to the years before and after the nuclear power station began operation
      and contrasted with rates in two similar counties in Florida (Polk and Volusia).
      Over the prolonged period 1950-2000, no unusual patterns of childhood cancer
      mortality were found for St Lucie County as a whole. In particular, no unusual
      patterns of childhood cancer mortality were seen in relation to the start-up of
      the St Lucie nuclear power station in 1976. Further, there were no significant
      differences in mortality between the study and comparison counties for any cancer
      in the time period after the power station was in operation. Relative rates for
      all childhood cancers and for childhood leukaemia were higher before the nuclear
      facility began operating than after, while rates of brain and other nervous
      tissue cancer were slightly lower in St Lucie County than in the two comparison
      counties for both time periods. Although definitive conclusions cannot be drawn
      from descriptive studies, these data provide no support for the hypothesis that
      the operation of the St Lucie nuclear power station has adversely affected the
      cancer mortality experience of county residents.

PMID- 16286688
TI  - Doses from radon and its decay products to children.
AB  - This paper considers doses from radon and decay products when inhaled or ingested
      by one year old infants and by ten year old children. Doses from decay products
      deposited on skin are also discussed. For inhalation and ingestion, the general
      pattern of doses to organs is broadly similar to that in adults. Much the largest
      doses are received by the organ of intake (respiratory tract and stomach
      respectively). Otherwise, tissues with higher fat content tend to receive
      somewhat higher doses from radon gas than other tissues. Dose coefficients (dose
      per unit intake factors) for children are generally larger than those for adults.
      However, total annual doses are more similar across the age groups because of
      smaller intakes of air and water by children. Radon decay products deposited on
      skin may be able to induce skin cancer. However, the location of the sensitive
      cells is not known with certainty and they may lie too deep to receive
      significant dose. If they are irradiated, it is likely that doses to children
      would be larger than for adults. The radiological significance of doses to
      children is discussed.

PMID- 16286689
TI  - Mapping variation in radon potential both between and within geological units.
AB  - Previously, the potential for high radon levels in UK houses has been mapped
      either on the basis of grouping the results of radon measurements in houses by
      grid squares or by geological units. In both cases, lognormal modelling of the
      distribution of radon concentrations was applied to allow the estimated
      proportion of houses above the UK radon Action Level (AL, 200 Bq m(-3)) to be
      mapped. This paper describes a method of combining the grid square and geological
      mapping methods to give more accurate maps than either method can provide
      separately. The land area is first divided up using a combination of bedrock and
      superficial geological characteristics derived from digital geological map data.
      Each different combination of geological characteristics may appear at the land
      surface in many discontinuous locations across the country. HPA has a database of
      over 430,000 houses in which long-term measurements of radon concentration have
      been made, and whose locations are accurately known. Each of these measurements
      is allocated to the appropriate bedrock--superficial geological combination
      underlying it. Taking each geological combination in turn, the spatial variation
      of radon potential is mapped, treating the combination as if it were continuous
      over the land area. All of the maps of radon potential within different
      geological combinations are then combined to produce a map of variation in radon
      potential over the whole land surface.

PMID- 16286690
TI  - Disaggregation and valuation of collective dose and global circulation dose.
AB  - This study is an extension of earlier work (Jones et al 2004 J. Radiol. Prot. 24
      13-27) using an adaptation of the PC-CREAM computer model (Mayall et al 1997 NRPB
      SR296 (EUR 17791 EN) (Chilton: NRPB)) applied to future discharge scenarios for
      the nuclear fuel reprocessing plant at Sellafield, Cumbria, UK. This work showed
      that, of the total 3700 person-Sv collective dose delivered to the world
      population over 500 years integration from a particular scenario (SF3), 95% is at
      levels of individual dose below 0.015 microSv y(-1). The collective dose
      delivered at individual dose rates below 0.015 microSv y(-1) reflects the
      contribution from globally circulating radionuclides, namely (3)H, (14)C, (85)Kr
      and (129)I. The methodology used in the earlier work could not break down the
      dose from globally circulating radionuclides into bands of individual dose; the
      principal aim of this study is to achieve such a breakdown. The results confirm
      that the global circulation dose is received in the very lowest bands i.e. all
      below 0.015 microSv y(-1) for atmospheric discharges, and all below 0.0015
      microSv y(-1) for discharges to the sea in the SF3 scenario. If account is taken
      of the argument that the monetary value of the detriment associated with
      collective dose should reduce with decreasing levels of individual dose or risk
      (Jackson et al 2004 J. Radiol. Prot. 24 41-59; NRPB 1993 Doc. NRPB 4 (2) 75-80)
      then it can be shown that the value of the detriment associated with discharges
      in the SF3 scenario would be substantially reduced compared with that derived
      from current conventional assumptions.

PMID- 16286691
TI  - Dose reconstruction of a Brazilian industrial gamma radiography partial-body
      overexposure case.
AB  - In May 2000, an operator of a (60)Co industrial gamma radiography apparatus,
      during a routine service, was involved in a partial-body radiological accident,
      which caused serious injuries to his left hand. Dose reconstruction was started
      aiming to assess the radiation doses, in order to assist the medical staff in the
      evaluation and prescription of suitable medical procedures for the patient's
      treatment and follow-up. This work presents the dose reconstruction used for
      assessment of the distribution of doses on the patient's left hand, which was
      made using two methods: physical and computational techniques. For the first
      technique a physical hand simulator was built. The computational method was
      performed using microcomputer software for external dose calculations, named
      'Visual Monte-Carlo-VMC', together with a hand voxel simulator. The values
      obtained through both methods for the distribution of absorbed doses on the
      operator's left hand were compared. About half of them were similar within a
      range of uncertainty of 20%.

PMID- 16286692
TI  - Fast retrospective determination of radon exposure with a sensitive alpha
      scintillation probe.
AB  - The background of a hand-held alpha ZnS scintillation probe of 44 cm(2) was
      reduced from the normal 50 counts per hour (cph) to 4 +/- 2 cph and the
      efficiency increased to 34%. The limit of detection for a 30 min measurement is
      now 5 Bq m(-2) Po-210 on glass surfaces, corresponding to about 200 Bq m(-3)
      indoor Rn-222 exposure for 20 years. The probe was successfully used for
      retrospective determination of radon exposure. The probe is simpler, faster and
      more convenient, and more economic than alpha spectrometry or nuclear track
      detectors currently used in the field of lung cancer epidemiology and long term
      radon exposure.

PMID- 16286693
TI  - Population dose distribution due to soil radioactivity concentration levels in 18
      cities across Nigeria.
AB  - The natural radioactivity concentrations in soil samples collected from 186
      locations across 18 cities in the six geo-political zones of Nigeria have been
      determined using gamma-ray spectrometry. Results show that the concentrations of
      (40)K, (238)U and (232)Th in the soil samples varied from below detection limits
      (BDL) to 1459.4 Bq kg(-1) with a mean of 73.3 +/- 18.5 Bq kg(-1) for (40)K,
      whereas for (238)U and (232)Th values varied from 9.2 to 113.7 Bq kg(-1) with a
      mean of 33.9 +/- 7.4 Bq kg(-1) and from BDL to 175.7 Bq kg(-1) with a mean of
      12.4 +/- 3.1 Bq kg(-1), respectively. The average gamma absorbed dose rate in air
      across the cities ranged between 19 +/- 5 and 88 +/- 44 nGy h(-1) and the gross
      mean was 42.0 +/- 21.0 nGy h(-1). Using available population data in the study
      areas, about 2.84% of the population is exposed to a radiation dose rate of less
      than 20 nGy h(-1), 52.40% to a radiation dose rate between 20 and 30 nGy h(-1),
      31% to a radiation dose rate between 30 and 60 nGy h(-1) and about 13.76% to dose
      rates greater than 60 nGy h(-1).

PMID- 16286694
TI  - The UK Committee on Radioactive Waste Management.
AB  - The UK Committee on Radioactive Waste Management is charged with recommending to
      Government, by July 2006, options for the long term management of the UK's
      radioactive waste legacy. These options should inspire public confidence. Now,
      more than halfway into the time allotted, we, as two former members of the
      Committee, express our concerns at the wayward approach that has been adopted.
      The Committee has placed emphasis on gaining public confidence but this has been
      done at the expense of recruiting the best scientific expertise in the management
      of radioactive waste, an act which we believe will actually undermine public
      confidence. Furthermore, given also the immense importance of this decision to
      public safety, national security and the national interest, we believe urgent
      steps should be taken to review the Committee's process, its management and its
      sponsorship.

PMID- 16286695
TI  - Comment on 'Personal photon dosemeter trial---Devonport Royal Dockyard' by R
      Collison.

PMID- 16286697
TI  - For better ICRP recommendations on the radiological protection system.

PMID- 16286700
TI  - Vertical linear self-motion perception during visual and inertial motion: more
      than weighted summation of sensory inputs.
AB  - We evaluated visual and vestibular contributions to vertical self motion
      perception by exposing subjects to various combinations of 0.2 Hz vertical linear
      oscillation and visual scene motion. The visual stimuli presented via a head
      mounted display consisted of video recordings of the test chamber from the
      perspective of the subject seated in the oscillator. In the dark, subjects
      accurately reported the amplitude of vertical linear oscillation with only a
      slight tendency to underestimate it. In the absence of inertial motion, even low
      amplitude oscillatory visual motion induced the perception of vertical self
      oscillation. When visual and vestibular stimulation were combined, self-motion
      perception persisted in the presence of large visual-vestibular discordances. A
      dynamic visual input with magnitude discrepancies tended to dominate the
      resulting apparent self-motion, but vestibular effects were also evident. With
      visual and vestibular stimulation either spatially or temporally out-of-phase
      with one another, the input that dominated depended on their amplitudes. High
      amplitude visual scene motion was almost completely dominant for the levels
      tested. These findings are inconsistent with self-motion perception being
      determined by simple weighted summation of visual and vestibular inputs and
      constitute evidence against sensory conflict models. They indicate that when the
      presented visual scene is an accurate representation of the physical test
      environment, it dominates over vestibular inputs in determining apparent spatial
      position relative to external space.

PMID- 16286699
TI  - Human ocular torsion and perceived roll responses to linear acceleration.
AB  - We investigated if human ocular torsion (OT) and perceived roll (PR) are elicited
      in response to either dynamic interaural linear acceleration or dynamic roll tilt
      of the gravito-inertial force (GIF). We expanded a previous study [26] that
      measured only OT across a limited frequency-range (from 0.35 Hz to 1 Hz) by
      simultaneously measuring OT and PR at three very low (0.01, 0.02 and 0.05 Hz) and
      one high (1 Hz) frequencies. Three experimental conditions were investigated: (1)
      Y-Upright with acceleration along the interaural (Y) axis while upright, (2) Y
      Supine with acceleration along the Y-axis while supine, and (3) Z-RED with
      acceleration along the rostro-caudal Z) axis with right-ear-down (RED). OT was
      measured by video-oculography, while PR was measured by use of a somatosensory
      bar. OT and PR were qualitatively different. Large OT responses were measured for
      Y-Upright and Y-Supine, while large perceived roll responses were observed for Y
      Upright and Z-RED. OT for Z-RED was small, and PR for Y-Supine was absent. In
      conclusion, OT and PR appear governed by qualitatively different neural
      mechanisms. OT appears mostly influenced by central low-pass filtering of
      interaural graviceptor cues, while PR appears mostly influenced by roll tilt of
      the GIF.

PMID- 16286701
TI  - Unbiased quantification of Scarpa's ganglion neurons in aminoglycoside
      ototoxicity.
AB  - While most studies have demonstrated damage to the cochlear and vestibular
      endorgan as the primary site of aminoglycoside toxicity, the effect on the
      primary afferent neurons of the vestibular ganglion remains to be determined.
      This study used the unbiased stereology-optical fractionator method to obtain
      estimates of the vestibular ganglion neuronal number. Archival temporal bone
      specimens from seven subjects with a history of gentamicin (n=3) and streptomycin
      (n=4) aminoglycoside ototoxicity were used. The post-ototoxicity survival time
      ranged from two months to 8 years, with an average of 2.2 years. Seven archival
      human temporal bone specimens from age-matched subjects with no history of
      audiovestibular symptoms or ototoxicity served as controls. Group means were
      compared using unpaired, two-tailed student's t test. The average vestibular
      ganglion neuronal number in the aminoglycoside ototoxicity group was 20, 733
      neurons (CV=0.073), which was significantly lower (p<0.005) than the average
      number in the age-matched control group of 24, 902 neurons (CV=0.109). These
      findings may be consistent with either retrograde degeneration or a direct
      neurotoxic effect of the aminoglycosides on the vestibular ganglion neuron.

PMID- 16286702
TI  - Biomechanics of horizontal canal benign paroxysmal positional vertigo.
AB  - Horizontal canal (HC) benign paroxysmal positional vertigo (HC-BPPV) is a
      vestibular disorder characterized by bouts of horizontal ocular nystagmus induced
      during reorientation of the head relative to gravity. The present report
      addresses the application of a morphologically descriptive 3-canal biomechanical
      model of the human membranous labyrinth to study gravity-dependent semicircular
      canal responses during this condition. The model estimates dynamic cupular and
      endolymph displacements elicited during HC-BPPV provocative diagnostic maneuvers
      and canalith repositioning procedures (CRPs). The activation latencies in
      response to an HC-BPPV provocative diagnostic test were predicted to vary
      depending upon the initial location of the canalith debris (e.g. within the HC
      lumen vs. in the ampulla). Results may explain why the onset latency of ocular
      nystagmus evoked by the Dix-Hallpike provocative maneuver for posterior canal
      BPPV are typically longer than the latencies evoked by analogous tests for HC
      BPPV. The model was further applied to assess the efficacy of a 360 degrees 
      rotation CRP for the treatment of canalithiasis HC-BPPV.

PMID- 16286703
TI  - The minimal ice water caloric test compared with established vestibular caloric
      test procedures.
AB  - Caloric testing of the vestibular labyrinth is usually performed by classical
      caloric test procedures (CCTP) using water warmed to 30 degrees C and 44 degrees
      C. Ice water irrigation (4 degrees C) is usually not performed, although it might
      be useful as a bedside test. To verify the validity of the Minimal Ice Water
      Caloric Test (MIWCT), comparative video-oculographic investigations were
      performed in 22 healthy subjects using ice water (0.5 ml, 1.0 ml, 2 ml), CCTP,
      and cold air (27 degrees C). Frequency, amplitude, slow phase velocity (SPV), the
      onset, and the duration of nystagmus were documented. After addition of three ice
      cubes, the temperature of conventional tap water (16 degrees C) fell within 13
      min to 4 degrees C. In pessimum position the subjects demonstrated no nystagmus
      response. Compared to CCTP, MIWCT was associated with a significantly later onset
      of nystagmus and a significant prolongation of the nystagmus reaction. In
      contrast to air stimulation (27 degrees C), a significant Spearman's correlation
      was noted between MIWCT (1 and 2 ml) and established CCTP in respect of essential
      nystagmus parameters (frequency, amplitude and SPV). Furthermore, MIWCT (0.5 and
      1 ml) showed a higher sensitivity and specificity with regard to the detection of
      canal paresis based on Jongkees' formula compared to stimulation with air 27
      degrees C. Thus, MIWCT appears to be a suitable procedure for bedside
      investigation of vestibular function outside the vestibular laboratory, e.g. in a
      hospital ward, where bedridden patients with vertigo occasionally require
      vestibular testing.

PMID- 16286704
TI  - Pancreatic hyperenzymemia: clinical significance and diagnostic approach.

PMID- 16286705
TI  - Value of laparoscopy in the staging of pancreatic cancer.
AB  - Pancreatic cancer is a devastating disease that swiftly robs patients of both
      quality and quantity of life. It is the fourth leading cause of cancer death in
      the United States. In 2003, there were 31,860 reported new cases with 31,270
      deaths occurring due to lack of effective therapy. Eighty percent of patients
      present with either advanced local or metastatic disease. Dynamic contrast
      enhanced computed tomography (CT) has become the current staging test of choice.
      Laparoscopic staging of pancreatic tumors with the addition of ultrasound can
      reveal intraparenchymal hepatic metastases, small peritoneal metastases, and
      critical retroperitoneal tumor-vessel relationships approaching the accuracy of
      open exploration to determine resectability without significantly increasing
      morbidity or mortality. However, given the current accuracy of high-quality CT,
      the routine use of diagnostic laparoscopy in pancreatic cancer is not warranted.
      Diagnostic laparoscopy is recommended in select patients with primary tumors
      greater than 4 cm, tumors in the body or tail of the pancreas, patients with
      equivocal findings of metastasis on CT, ascites, or clinical or laboratory
      findings suggesting advanced disease such as marked weight loss, hypoalbuminemia,
      and elevated CA 19-9.

PMID- 16286706
TI  - Computed tomography severity index, APACHE II score, and serum CRP concentration
      for predicting the severity of acute pancreatitis.
AB  - CONTEXT: The assessment of the severity of pancreatitis is important for proper
      management of this challenging disease. A highly accurate system which could
      predict the severity and identify the local extent and complications of a serious
      inflammation, is beneficial for patient outcome. OBJECTIVE: The aim was to
      establish the value of the computed tomography severity index in predicting the
      severity of acute pancreatitis and to compare it with the accuracy of the APACHE
      II score and serum CRP concentrations. DESIGN: Prospective clinical series.
      PATIENTS: Fifty-five consecutive patients (37 women, 18 men; mean age 57 years)
      with a clinical and laboratory diagnosis of acute pancreatitis. INTERVENTIONS:
      Clinical evaluation, biochemical analysis of blood and contrast-enhanced
      abdominal CT. MAIN OUTCOME MEASURES: Computed tomography severity index within
      the first 5 days, serum CRP level, and clinical APACHE II score at 48 hours after
      admission. RESULTS: Thirteen patients had severe pancreatitis according to the
      Atlanta classification. The mean values of predictive markers in the mild and the
      severe pancreatitis groups were: computed tomography severity index 1.26 and 6.30
      (P<0.001); APACHE II 4.14 and 8.61 (P<0.001); and CRP 96.0 mg/L and 192.4 mg/L
      (P<0.001), respectively. The sensitivity, specificity, positive predictive value,
      negative predictive value and accuracy were calculated for the CTSI (greater than
      3: 85%, 98%, 92%, 95%, and 95%), for APACHE II (equal to, or greater than 7: 62%,
      86%, 57%, 88%, and 80%) and for CRP (equal to, or greater than 150 mg/L: 85%,
      74%, 50%, 94%, and 76%). CONCLUSION: The computed tomography severity index is a
      reliable method for staging the severity of acute pancreatitis; moreover, CT has
      the ability of showing the local extent of the inflammation and the occurrence of
      local complications.

PMID- 16286707
TI  - Endoscopic ultrasonography and alcoholic patients: can one predict early
      pancreatic tissue abnormalities?
AB  - CONTEXT: The diagnosis of chronic pancreatitis in early stages remains
      challenging and agreement between various methods is poor. Alcohol consumption is
      the most important cause of chronic pancreatitis. OBJECTIVE: The aim of this
      study was to evaluate the endosonographic evidence of pancreatic disease in
      patients with alcohol abuse. SETTING: Consecutive patients referred for
      endoscopic ultrasonography for various indications between May 2001 and December
      2003. PATIENTS: Two hundred twenty-eight patients were enrolled in the study. One
      hundred 89 patients were studied; 39 (17.1%) were excluded because the pancreas
      could not be completely assessed (n=23) or because a previous diagnosis of
      chronic pancreatitis and/or pancreatic neoplasm was suspected (n=16). DESIGN:
      Prospective study. The patients were divided into 2 groups: alcoholics (n=17) and
      non-alcoholics (n=172). MAIN OUTCOME MEASURE: The assessment of pancreatic
      disease according to parenchymal and ductal changes as previously described by
      Catalano and Sahai (scores 1 and 2, respectively). RESULTS: The male:female ratio
      was 7.5 and 0.9 in the alcoholic and the non-alcoholic groups, respectively
      (P=0.002). Mean ages were 53.0 and 47.8 years, respectively (P=0.156). Alcoholic
      patients had significantly (P<0.001) more endosonographic abnormalities than non
      alcoholics for both scores. A ROC curve comparison between patients and controls
      showed that the best specificity and sensitivity combination was obtained for the
      number of EUS features greater than 1 and 2 for the scores 1 and 2, respectively.
      CONCLUSION: Alcoholic patients had significantly more endosonographic
      abnormalities reflecting possible early changes of chronic pancreatitis. By using
      reported scores, values up to 1 or 2 can be seen in patients with no risk for
      pancreatitis, suggesting that chronic pancreatitis should be considered only for
      scores equal to or greater than 2 or 3 for scores 1 and 2, respectively.

PMID- 16286708
TI  - AgNOR count and subjective AgNOR pattern assessment (SAPA) score in carcinoma of
      the pancreatic head including periampullary tumors.
AB  - CONTEXT: Only a few studies are available in the literature regarding the AgNOR
      (argyrophilic nucleolar organizer region) count in pancreatic adenocarcinoma but
      studies on the SAPA (subjective AgNOR pattern assessment) score are completely
      lacking. OBJECTIVE: We attempted to estimate the AgNOR count and the SAPA score
      in carcinoma of the pancreatic head including periampullary tumors and to
      correlate them with other various clinico-histological parameters. SETTING:
      Patients undergoing pancreatic resection at the University Hospital, Banaras
      Hindu University, Varanasi, India. PATIENTS: Twenty-four cases of carcinoma of
      the pancreatic head including periampullary tumors. In addition, on the resected
      specimen of the pancreas, the area which was normal was chosen and, in that
      normal tissue, the AgNOR was also studied. MAIN OUTCOME MEASURES: Patients were
      studied for the AgNOR count and the SAPA score, and the values were correlated
      with the size of the tumor, the type of tumor and histological type and grade of
      tumor. RESULTS: The values of the AgNOR count and the SAPA score were
      significantly higher in cases of pancreatic cancer than in the healthy pancreas.
      The AgNOR count was 1.6+/-0.1 in the healthy pancreas while it was 2.8+/-0.5 in
      cases of pancreatic carcinoma (P<0.001). The SAPA score was 5.6+/-0.2 in the
      healthy pancreas while it was 8.0+/-1.4 in pancreatic carcinoma (P<0.001). Tumors
      less than or equal to 2 cm in size had an AgNOR count of 2.6+/-0.08 while the
      AgNOR count was 3.4+/-0.02 in tumors larger than 2 cm (P<0.001). The SAPA score
      was also higher in tumors greater than 2 cm in size (7.3+/-0.2 vs. 9.4+/-0.8;
      P<0.001). Periampullary tumors had a significantly lower (P<0.001) AgNOR count
      (2.7+/-0.06) and SAPA score (7.8+/-0.2) as compared to carcinoma of the head of
      the pancreas (AgNOR count 3.3+/-0.03 and SAPA score 9.2+/-0.7). Well
      differentiated carcinomas had significantly lower AgNOR counts as compared to
      other tumors except acinar cell carcinomas since acinar cell carcinomas are also
      well-differentiated tumors. The SAPA score was also higher in moderately
      differentiated tumors and the difference between moderately-differentiated tumor
      and other types of tumors was significant although there was no significant
      difference between cystadenocarcinomas and unclassified tumors, and between
      acinar cell carcinomas and well-differentiated tumors on SAPA scoring.
      CONCLUSIONS: The values of the AgNOR count and the SAPA score are well-correlated
      with the size of the tumor, the type of tumor and the histological grade.

PMID- 16286709
TI  - Radiofrequency ablation of the pancreas. I: Definition of optimal thermal kinetic
      parameters and the effect of simulated portal venous circulation in an ex-vivo
      porcine model.
AB  - CONTEXT: Radiofrequency ablation of pancreatic tumours carries a risk of injury
      to important structures such as the bile duct and duodenum. We have recently
      developed an ex-vivo model of radiofrequency ablation of the porcine pancreas.
      OBJECTIVE: This study evaluates the effect of variations in probe temperature,
      duration of ablation and simulated portal venous flow on radiofrequency-induced
      injury. SPECIMEN RETRIEVAL: Pancreata of 30 6-month-old healthy pigs undergoing
      sacrifice in a commercial abattoir were used. INTERVENTIONS: Radiofrequency
      energy was applied to a pre-marked area of the pancreatic head. Pancreatic head
      biopsies were taken after ablation to incorporate duodenum, portal vein and bile
      duct respectively and frozen in liquid nitrogen. For each experiment a portion of
      the tail of the pancreas was studied as non-ablated control. Paired slides using
      haematoxylin and eosin (H&E) and nicotinamide adenine dinucleotide (NADH) stains
      were prepared. MAIN OUTCOME MEASURES: The effects of variation in target
      temperature (100 degrees C to 80 degrees C), duration of ablation and of
      simulated portal perfusion were studied. RESULTS: Optimal thermal kinetic
      characteristics were produced by a target temperature of 90 degrees C applied for
      5 minutes. At this temperature there was ablation of pancreas without injury to
      adjacent viscera. Higher temperatures resulted in injury to the bile duct and
      portal vein. Simulated portal circulation had no effect on ablation. CONCLUSIONS:
      In this ex-vivo study radiofrequency produced a temperature and duration
      dependent ablation with the optimal characteristics being 90 degrees C for 5
      minutes.

PMID- 16286710
TI  - Radiofrequency ablation of the pancreas. II: Intra-operative ablation of non
      resectable pancreatic cancer. A description of technique and initial outcome.
AB  - CONTEXT: There is little reported experience of radiofrequency ablation of
      pancreatic tumours. Our group has reported the development of a porcine
      pancreatic model of radiofrequency ablation of the pancreas. This brief report
      details the application of this technique to clinical practice. CASE REPORT: A 58
      year-old man with metastatic pancreatic tumour underwent operative radiofrequency
      ablation. An operative approach was utilised to protect the stomach and
      transverse colon and also to prevent thermal injury to the inferior vena cava. In
      addition, the operative technique was combined with prophylactic
      hepaticojejunostomy and gastrojejunostomy to anticipate ablation-related biliary
      injury or duodenal stenosis. A post-ablation CT scan two weeks after the
      procedure confirmed radiological evidence of ablation. The patient remained well
      until his death, 3 months after surgery. CONCLUSION: This report demonstrates
      that operative radiofrequency ablation is feasible and was safely carried out in
      this case. More experience is required to assess the spectrum of complications
      and if there is true oncological efficacy.

PMID- 16286711
TI  - An intra-hepatic pancreatic pseudocyst successfully treated endoscopic
      transpapillary drainage alone.
AB  - CONTEXT: An intra-hepatic pseudocyst is a very rare complication of acute and
      chronic pancreatitis with less than thirty cases described in the literature.
      Successful resolution of intra-hepatic pseudocysts with endoscopic transpapillary
      nasopancreatic drain placement has not previously been described. CASE REPORT: We
      report the case of a 34-year-old male with chronic idiopathic non-calcific
      pancreatitis, anomalous pancreatobiliary junction and a large intra-hepatic
      pancreatic pseudocyst along with a large abdominal pseudocyst who was
      successfully treated by endoscopic transpapillary nasopancreatic drainage alone.
      CONCLUSION: Pancreatic pseudocysts can present as intra-hepatic cystic lesions
      and communicating intra-hepatic pseudocysts can be successfully treated by
      endoscopic transpapillary nasopancreatic drainage alone.

PMID- 16286713
TI  - Biliary obstruction due to isolated pancreatic tuberculosis.

PMID- 16286712
TI  - Pancreatic tuberculosis diagnosed with endoscopic ultrasound guided fine needle
      aspiration.
AB  - CONTEXT: Isolated pancreatic tuberculosis is rare in the Western world. Its
      clinical presentation often mimics pancreatic malignancy and the diagnosis is
      usually not suspected or confirmed prior to laparotomy. Endoscopic ultrasound
      guided fine needle aspiration cytology has proved to be an excellent tool for the
      cytological diagnosis of pancreatic and peripancreatic masses. However, this
      technique has not been reported for diagnosing pancreatic or peripancreatic
      tuberculosis. CASE REPORT: We describe a 57-year-old South Asian man with
      pancreatic tuberculosis who presented with fever of undetermined origin and a
      pancreatic mass on imaging. He was successfully treated with anti-tuberculosis
      regimen following confirmation of his diagnosis with endoscopic ultrasound guided
      fine needle aspiration cytology. CONCLUSIONS: Pancreatic tuberculosis should be
      suspected in patients having a pancreatic mass, particularly if patient presents
      with fever and lived in, or traveled to, an area of endemic tuberculosis or
      exposed to tuberculosis. When the diagnosis is suspected, endoscopic ultrasound
      guided fine needle aspiration cytology of the pancreatic lesion can confirm the
      diagnosis and so avoid an unnecessary explorative laparotomy or pancreatic
      resection.

PMID- 16286714
TI  - Idiosyncratic pancreatitis associated with perindopril.

PMID- 16286716
TI  - Diagnosis of autoimmune pancreatitis: clinical and histological assessment.

PMID- 16286717
TI  - Phylogenetic analyses of fat body endosymbionts reveal differences in invasion
      times of blaberid wood-feeding cockroaches (Blaberidae: Panesthiinae) into the
      Japanese archipelago.
AB  - Cockroaches have endosymbiotic bacteria in their fat bodies. Recent molecular
      phylogenetic analyses on both hosts and endosymbionts have revealed that co
      evolution has occurred throughout the history of cockroaches and termites. Co
      cladogenesis was also shown among closely related taxa (woodroach genus
      Cryptocercus; Cryptocercidae), and thus endosymbiont data are likely to be useful
      for biogeographical analyses. To test the possibility of co-cladogenesis among
      inter-and intraspecific taxa, as well as the utility of endosymbiont data for
      inferring biogeographical scenarios, we analyzed rRNA genes of endosymbionts of
      Japanese and Taiwanese Panesthiinae (Salganea and Panesthia; Blaberidae), on
      which phylogenetic analyses previously had been performed based on the
      mitochondrial genes. Statistical analyses on the topologies inferred from both
      endosymbiont and host mitochondria genes showed that co-cladogenesis has
      occurred. The endosymbiont sequences examined appear to have evolved in a clock
      like manner, and their rate of evolution based on the host fossil data showed a
      major difference in the time of invasion of the two Japanese genera, that is
      congruent with the recent analyses of their mitochondrial genes.

PMID- 16286718
TI  - Comparative phylogeography between the ermine Mustela erminea and the least
      weasel M. nivalis of Palaearctic and Nearctic regions, based on analysis of
      mitochondrial DNA control region sequences.
AB  - Phylogeography of the ermine Mustela erminea and the least weasel M. nivalis from
      Palaearctic and Nearctic regions were investigated based on mitochondrial DNA
      control region sequences. Mustela erminea exhibited a very low level of genetic
      variation, and geographic structures among populations were unclear. This may
      indicate that M. erminea recently reoccupied a wide territory in Eurasia
      following the last glacial retreat. In comparison with M. erminea, genetic
      variations within and among populations of M. nivalis were much greater.
      Molecular phylogenetic relationships showed that two lineages of M. nivalis
      occurred in the Holarctic region: one spread from the Eurasian region to North
      America, and the other occurred in south-eastern Europe, the Caucasus and Central
      Asia. The results suggest either mitochondrial DNA introgression among
      populations of south-eastern Europe, the Caucasus and Central Asia, or ancestral
      polymorphisms remaining in those populations. Contrastive phylogeographic
      patterns between the two mustelid species could reflect differences of their
      migration histories in Eurasia after the last glacial age.

PMID- 16286719
TI  - Discrimination of conspecific individuals via cuticular pheromones by males of
      the cricket Gryllus bimaculatus.
AB  - Cuticular substances on the body surface of crickets serve as pheromones that
      elicit a variety of different behaviors in male crickets. Antennal contact
      between males and females resulted in courtship behavior, and that between two
      males resulted in aggressive displays. As a first step in elucidating how
      crickets recognize and discriminate individuals, behavioral responses of male
      individuals to cuticular substances of conspecific males or females were
      investigated. The behavioral responses of males to antennal or palpal stimulation
      with an isolated antenna from a male or a female were recorded. To both antennal
      and palpal stimulation with female antennae, the majority of males responded with
      courtship behavior; to stimulation with male antennae, males responded with
      aggressive displays. To gain insight into the chemical nature of the behaviorally
      relevant components, isolated antennae were washed in either n-hexane, acetone or
      ethanol before behavior assays. Washed antennae no longer elicited courtship or
      aggressive responses in males. Next, polypropylene fibers were smeared with
      substances from the body surface of females and used for antennal stimulation.
      This experiment showed that the quality and quantity of cuticular substances
      appear to be highly age-dependent. Significantly more males responded with
      courtship behavior to cuticular substances from younger females. Isolated males
      generally showed higher levels of aggression than males reared in groups. Grouped
      males also were more likely to display courtship behavior towards antennae from
      younger females, and aggressive behavior towards antennae from older females.
      These results suggest that male discrimination of mating partners depends on the
      nature of female cuticular substances.

PMID- 16286720
TI  - Sex differences in the telencephalic song control circuitry in Bengalese finches
      (Lonchura striata var. domestica).
AB  - Bengalese finches, Lonchura striata, are extremely sexually dimorphic in their
      singing behavior; males sing complex songs, whereas females do not sing at all.
      This study describes the developmental differentiation of the brain song system
      in Bengalese finches. Nissl staining was used to measure the volumes of four
      telencephalic song nuclei: Area X, HVC, the robust nucleus of the arcopallium
      (RA), and the lateral portion of the magnocellular nucleus of the anterior
      nidopallium (LMAN). In juveniles (circa 35 days old), Area X and the HVC were
      well developed in males, while they were absent or not discernable in females.
      The RA was much larger in males but barely discernable in females. In males, the
      volumes of Area X and the RA increased further into adulthood, but that of the
      HVC remained unchanged. The LMAN volume was greater in juveniles than in adults,
      and there was no difference in the LMAN volume between the sexes. The overall
      tendency was similar to that described in zebra finches, except for the volume of
      the RA, where the degree of sexual dimorphism is larger and the timing of
      differentiation occurs earlier in Bengalese finches. Motor learning of the song
      continues until day 90 in zebra finches, but up to day 120 in Bengalese finches.
      Earlier neural differentiation and a longer learning period in Bengalese finches
      compared with zebra finches may be related to the more elaborate song structures
      of Bengalese finches.

PMID- 16286721
TI  - Interactions between Caenorhabditis elegans individuals during chemotactic
      response.
AB  - The chemotactic response of the nematode Caenorhabditis elegans is known to be
      affected by the population density on an assay plate, suggesting the existence of
      interactions between individual animals. To clarify the interactions between
      individuals during chemotaxis, we investigated the effect of population density
      at an attractant area on the chemotactic response to water-soluble sodium acetate
      and odorant diacetyl using wild-type N2 animals and daf-22 (m130) mutants, which
      have defective pheromone secretion but can sense pheromone. The chemotaxis index
      of N2 animals at 90 min of the assay negatively correlated with the number of
      animals on the assay plate regardless of the type of attractant used (p<0.01). On
      the other hand, there was no significant difference in the chemotaxis indices of
      daf-22 (m130) mutants for either of the attractants between the low-and high
      population groups. When daf-22 (m130) mutants of a high population density were
      placed at the attractant location in advance, the chemotaxis index of N2 animals
      was almost the same as that in the control assay in which no animals were placed
      at the attractant location in advance. When N2 animals of a high population
      density were placed at the attractant location in advance, the chemotaxis indices
      of N2 animals and daf-22 (m130) mutants were significantly smaller than those
      obtained in the control assay (p<0.05). In the absence of an attractant, we
      observed a decline in the fraction of animals in the neighborhood of N2 animals
      of a high population density, although the nematodes were not influenced by daf
      22 (m130) mutants of a high population density. These results suggest that the
      attraction of nematodes to chemicals is inhibited by an increase in the
      concentration of the pheromone generated by N2 animals at the attractant
      location.

PMID- 16286722
TI  - Single-chain tissue-type plasminogen activator is a substrate of mouse glandular
      kallikrein 24.
AB  - Leydig cells of the adult mouse testis express at a detectable level three
      distinct glandular (tissue) kallikrein genes: mKlk21, mKlk24, and mKlk27.
      Recently, the proteins encoded by these genes were characterized using active
      recombinant proteases, but their roles in the mouse testis remained to be
      determined. The present study showed that among the proteases, mK24 markedly
      enhanced the activity of human recombinant single-chain tissue-type plasminogen
      activator when the two were incubated together. This activation was found to be
      due to proteolytic conversion of the single-chain enzyme to a two-chain form. The
      expression of tissue-type plasminogen activator in interstitial Leydig cells was
      demonstrated by RT-PCR and immunohistochemical analyses. The primary culture
      medium of adult male testicular Leydig cells contained immunoreactive substances
      recognized by anti-mK24 antibodies. In addition, the same medium was capable of
      converting the single-chain plasminogen activator to the two-chain protein. These
      results suggest that mK24 may play a role in the degradation of extracellular
      matrix proteins in the interstitial area surrounding the Leydig cells of the
      adult mouse testis, due not only to its own activity, but also to that of plasmin
      produced by the single-chain tissue-type plasminogen activator-converting
      activity of mK24.

PMID- 16286723
TI  - Isolation of Ef silicatein and Ef lectin as molecular markers for sclerocytes and
      cells involved in innate immunity in the freshwater sponge Ephydatia fluviatilis.
AB  - Sponges (phylum Porifera) have remarkable regenerative and reconstitutive
      abilities and represent evolutionarily the oldest metazoans. To investigate
      sponge stem cell differentiation, we have focused on the asexual reproductive
      system in the freshwater sponge Ephydatia fluviatilis. During germination,
      thousands of stem cells proliferate and differentiate to form a fully functional
      sponge. As an initial step of our investigation of stem cell (archeocyte)
      differentiation, we isolated molecular markers for two differentiated cell types:
      spicule-making sclerocyte cells, and cells involved in innate immunity.
      Sclerocyte lineage-specific Ef silicatein shares 45% to 62% identity with other
      sponge silicateins. As in situ hybridization of Ef silicatein specifically
      detects archeocytes possibly committed to sclerocytes, as well as sclerocytes
      with an immature or mature spicule, therefore covering all the developmental
      stages, we conclude that Ef silicatein is a suitable sclerocyte lineage marker.
      Ef lectin, a marker for the cell type involved in innate immunity, shares 59% to
      65% identity with the marine sponge Suberites domuncula galactose-binding protein
      (Sd GBP) and horseshoe crab Tachypleus tridentatus tachylectin1/lectinL6. Since
      Sd GBP and tachylectin1 are known to bind to bacterial lipopolysaccharides and
      inhibit the growth of bacteria, Ef lectin may have a similar function and be
      expressed in a specialized type of cell involved in defense against invading
      bacteria. Ef lectin mRNA and protein are not expressed in early stages of
      development, but are detected in late stages. Therefore, Ef lectin may be
      specifically expressed in differentiating and/or differentiated cells. We suggest
      Ef lectin as a marker for cells that assume innate immunity in freshwater
      sponges.

PMID- 16286724
TI  - Distribution of immunoreactivities for adenohypophysial hormones in the pituitary
      gland of the polypteriform fish, Polypterus endlicheri.
AB  - Polypteriform fish constitutes the most primitive living descendent of the
      ancient bony fish. In polypteriform fish, only proopiomelanocortin (POMC) has
      been identified so far in the adenohypophysis, which is surprising in view of
      their evolutionary importance. In the present study, distribution of
      immunoreactive adenohypophysial hormones was examined in juvenile individuals of
      Polypterus endlicheri. Antisera to tetrapod and fish adenohypophysial hormones
      were used as immunostaining probes. Adrenocorticotropin (ACTH)-like cells were
      detected by antisera to salmon POMC N-terminal peptide, porcine ACTH and
      mammalian alpha-melanotropin (MSH), and were distributed in the rostral pars
      distalis in close proximity to the hypophysial duct. MSH-like cells were found in
      the pars intermedia, and were stained by anti-salmon N-Ac-beta-endorphin II as
      well as anti-mammalian alpha-MSH and anti-salmon POMC-N terminal peptide.
      Prolactin (PRL)-like cells were detected only after application of anti-sturgeon
      PRL, and were distributed in the rostral pars distalis, where PRL-positive
      material was found in columnar mucinous cells lining the diverticuli of the
      hypophysial duct. Growth hormone (GH)-like cells were stained with antisera to
      sturgeon GH, human GH, salmon GH and blue shark GH, and were distributed in the
      proximal pars distalis. Somatolactin (SL)-like cells were stained with anti
      salmon SL, and were distributed in the pars intermedia. Two types of glycoprotein
      hormone-positive cells were detected in the proximal pars distalis. Although both
      types of cells were stained with several antisera to glycoprotein hormones, such
      as sturgeon LHbeta and salmon LHbeta, it was difficult to know which types of
      cells produce LH, FSH, or TSH. Thus, the present study revealed seven types of
      adenohypophysial hormone-like cells in the Polypterus pituitary gland, which may
      provide the morphological basis for better understanding on evolution of the
      pituitary gland and the adenohypophysial hormones in vertebrates.

PMID- 16286725
TI  - Identification of thyroid hormone-responsive genes in a chicken hepatoma cell
      line, LMH.
AB  - Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that
      regulate the transcription of multiple thyroid hormone (TH)-responsive genes. Our
      study aimed to identify TH-responsive genes in an estrogen-responsive chicken
      hepatoma cell line, LMH. RNA was prepared from cells treated with or without 10(
      8) M 3,3',5-triiodothyronine (T3) for 24 h and was analyzed by differential
      display. At least six cDNAs were detected whose transcript increased in the
      presence of T3, and four of them were cloned. The four candidate TH-responsive
      genes that were identified had high similarity (>83%) to known chicken or
      mammalian genes, which included the ribosomal protein L7 gene; the cytoplasmic
      dynein heavy chain gene; the scaffold attachment factor A (SAF-A) gene, also
      known as heterogeneous nuclear ribonucleoprotein U (hnRNP U); and a gene for an
      unknown protein. Real-time PCR confirmed that the transcription of the four genes
      was responsive to T3; their transcript levels increased from four to eleven times
      with the administration of T3. The amount of TRbeta transcript did not change
      with the administration of T3. The physiological reasons for the activation of
      these genes and the utility of this cell line are discussed.

PMID- 16286726
TI  - Genetic variability among freshwater mussel Anodonta woodiana (Lea, 1834)
      (Bivalvia: Unionidae) populations recently introduced in Poland.
AB  - The alien Chinese mussel Anodonta woodiana was first reported in Poland in the
      system of heated lakes near Konin in 1993. Genetic studies with use of three
      molecular techniques (isoenzyme electrophoresis, PCR-RFLP and sequence analysis
      of a COI gene fragment) were carried out on the Polish first populations of A.
      woodiana. The studies have revealed low genetic variation between the populations
      (Nei's genetic distance for 12 loci ranged 0.000 to 0.007) as well as their
      considerable polymorphism. Each population averaged 2.28 alleles per locus, 2.72
      alleles per polymorphic locus, and 75% polymorphic loci. Restriction analysis of
      the COI gene fragment have not revealed variability between the analysed
      specimens, including males and females. Restriction enzymes, ScrFI, Csp6I, and
      EcoRI used in the COI gene fragment PCR-RFLP generate distinct restriction
      patterns, which can be molecular markers for A. woodiana. The sequence obtained
      for COI fragment was the same in the examined female and male specimens and
      represents F mitotype (DNA was isolated from somatic tissues). The divergence
      between A. woodiana F and M mitotypes is high (34%), however it remains within
      the range of the general character of the DUI (doubly uniparental inheritance)
      phenomenon in freshwater bivalves (Unionidae).

PMID- 16286728
TI  - Peripheral plasma progesterone: a marker for determining cyclicity in yaks
      (Poephagus grunniens L.).
AB  - An attempt was made to determine cyclicity in yaks using plasma progesterone
      during the breeding and non-breeding seasons. Fifteen non-lactating yaks were
      used in this experiment. During the breeding season (July to November), blood
      samples were collected from 8 yaks at least twice weekly until estrus was
      observed and then at 2 days interval for 30 days. During the non-breeding season
      (February to March), blood samples were collected from the same number of yaks at
      2-day interval for 30 days. Progesterone was determined in plasma samples by
      radioimmunoassay. During the breeding season, plasma progesterone at estrus was
      basal (< or = 0.2 ng/ml). Concentrations increased thereafter with a sharp
      increase during the late luteal phase, typically reaching peak levels around day
      15. Concentrations then declined rapidly over the following 4 days, reaching
      basal levels at estrus. A high proportion (66.7%) of potential estrous periods
      (based on progesterone concentrations) went undetected, indicating that silent or
      weak estrus was a prominent problem in yak cows. During the non-breeding season,
      three animals were found to be cycling as determined by the patterns of plasma
      progesterone. Yet, behavioral symptoms of estrus were not observed in any of
      these yak cows. We conclude that peripheral plasma progesterone concentrations
      can be used to monitor cyclicity in yak cows effectively.

PMID- 16286727
TI  - Generation of knock-in mice carrying third cones with spectral sensitivity
      different from S and L cones.
AB  - Red-green color vision in primates is unique in the sense that it is mediated by
      two photoreceptor cells that are indistinguishable in all aspects except for
      their visual pigments. In order to generate an animal model for investigation of
      the interaction between red-green inputs at the molecular level, we applied knock
      in technology and X-chromosome inactivation machinery to make a mouse model with
      cone cells possessing visual pigments with different spectral sensitivities. We
      introduced a S308A point mutation into the Green opsin gene allele on the X
      chromosome. This manipulation generated a 24 nm red-shift of absorption maximum
      in the cone pigment with negligible functional differences in other molecular
      properties. Amplitudes of responses in ERG and ganglion cell recordings of
      homozygotes were similar to those of wild-types, although the spectral
      sensitivities differed. Heterozygotes showed variable spectral sensitivities of
      ganglion cell responses due to the different integration of the native and the
      S308A cone inputs on the dendritic fields. In situ hybridization experiments
      showed that cone cells with respective pigments formed patch-like clusters of
      specific L cone-types, approximately 30 mum in diameter, which were randomly
      distributed in the dorsal region of the retinas. Since the patch-like clustering
      was arranged by X-inactivation, such clustering could be present in the
      peripheral retinas of New World monkeys with polymorphic L pigments, indicating
      that our mice would be a suitable model to study evolution of the mammalian color
      vision system.

PMID- 16286729
TI  - Sex reversal in the medaka Oryzias latipes by brief exposure of early embryos to
      estradiol-17beta.
AB  - To induce sex reversal of male to female, freshly-fertilized eggs of the S-rR
      strain medaka (Oryzias latipes) were immersed in saline containing estradiol
      17beta (E2) in different concentrations for various durations until hatching.
      Results of the present experiment showed that the immersion duration in 1
      microg/ml E2 to induce 100% reversal of sex differentiation in the genotypic
      males was enough only for one day (24 hr) post-fertilization (dpf) and that
      treatment with E2 for 1 dpf resulted in a dose-dependent manner with the maximum
      sex reversal of 100% at 1 microg/ml. To ascertain early developmental periods
      efficacious for inducing sex reversal, additional brief immersion treatments of
      eggs with E2 were further performed individually for four different early
      developmental periods (Stages 4-9, 10-12, 13-15 and 16-18) within 1 dpf. As a
      result, induction of sex reversal was observed in all these short immersion
      periods without any restricted efficacy. Between both experimental and control
      groups treated with or without E2 for 1 dpf, differences in the number of germ
      cells in a gonad were compared in newly-hatched fry. It was found that gonads of
      the genotypic males (XY) treated with E2 revealed the female type which contained
      many germ cells with much dividing activity. These data suggest that a possible
      switch mechanism that exogenous E2 could trigger to change the genetic cascades
      involved in sex determination upon fertilization exists in early developmental
      stages.

PMID- 16286730
TI  - Risk factors for primary intracerebral hemorrhage: a population-based nested case
      control study.
AB  - PURPOSE: In this population-based study, risk factors for primary intracerebral
      hemorrhage (PICH) and PICH subtypes were explored in a nested case-control
      design. METHOD: Risk factors were determined in 22,444 men and 10,902 women (mean
      age 47 years) who participated in a health-screening programme between 1974 and
      1991. 147 subjects with CT or autopsy-verified first-ever PICH during the follow
      up period (mean 14 years) were compared with 1,029 stroke-free controls, matched
      for age, sex and screening-year. RESULTS: As compared to controls, PICH cases had
      significantly higher blood pressure (135/91 vs. 127/85 mm Hg), triglycerides (1.7
      vs. 1.4 mmol/l), BMI (25.5 vs. 24.8) and shorter stature (1.73 vs. 1.74 m).
      Diabetes (6.9 vs. 2.8 %) and history of psychiatric morbidity (19.7 vs. 11.0 %)
      were more common in PICH cases and more of them were living alone (35.4 vs.
      25.5%). After adjustment in a backward logistic regression model, high systolic
      blood pressure, diabetes, high triglycerides, short stature and psychiatric
      morbidity remained significantly associated with PICH. As compared to the control
      group, high systolic blood pressure was significantly associated both with
      nonlobar and lobar PICH. Diabetes and psychiatric morbidity were associated with
      nonlobar PICH. Smoking doubled the risk for lobar PICH, but was unrelated to
      nonlobar PICH. CONCLUSION: In this prospective population-based study,
      hypertension, diabetes, height, triglycerides and psychiatric morbidity were risk
      factors for PICH. Smoking was a risk factor for lobar PICH only.

PMID- 16286731
TI  - Aging adversely affects postinfarction inflammatory response and early left
      ventricular remodeling after reperfused acute anterior myocardial infarction.
AB  - BACKGROUND AND AIMS: We have demonstrated that an increased peak serum C-reactive
      protein (CRP) level after acute myocardial infarction (AMI) was a major predictor
      of left ventricular (LV) remodeling. We sought to clarify the effect of aging on
      the postinfarction inflammatory response and LV remodeling. METHODS: We studied
      102 patients who underwent primary angioplasty for a first anterior Q-wave AMI.
      Serum CRP levels, plasma neurohormones and interleukin-6 (IL-6) levels, and LV
      volume by left ventriculography were serially measured. Patients were divided
      into two groups according to their age (>or=70 years, n=33; <70 years, n=69).
      RESULTS: There was no difference in use of cardiovascular drugs and coronary
      angiographic findings. Older patients had a greater increase in LV end-diastolic
      volume during 2 weeks after AMI (p=0.0007) and a higher peak CRP level (12.4+/
      7.3 vs. 5.5+/-4.2 mg/dl, p<0.0001), although peak CK level was comparable between
      the two groups. Plasma atrial natriuretic peptide, brain natriuretic peptide and
      IL-6 levels were higher in older patients at 2 weeks and 6 months after AMI.
      CONCLUSIONS: Augmented and prolonged activation of the inflammatory system after
      AMI was observed in older patients, in association with exaggerated LV
      remodeling. Aging may adversely affect LV remodeling through modification of the
      inflammatory response after AMI.

PMID- 16286732
TI  - Swallow syncope, a case report and review of the literature.
AB  - Swallow syncope is a relatively rare syndrome that is treatable when diagnosed. A
      66-year-old woman was referred to the department of cardiology because she had
      been suffering from recurrent syncopal attacks associated with swallowing. An
      ambulatory electrocardiogram revealed atrial and ventricular asystoles
      immediately after swallowing soup or tea that were reproducible (max. RR 3.5 s).
      An electrophysiological study did not detect sinus nodal or atrioventricular
      nodal dysfunction. The patient had no underlying esophageal disease or cardiac
      disorder. The patient's symptoms resolved after permanent pacemaker implantation.
      This report reviews the diagnosis, mechanism and management of swallow syncope.

PMID- 16286733
TI  - Aspirin, warfarin and a thienopyridine for acute coronary syndromes.
AB  - BACKGROUND: Although clopidogrel and aspirin (dual therapy, DT) are used for
      acute coronary syndrome (ACS), sometimes treatment with warfarin (triple therapy,
      TT) is required. AIM: To determine the incidence, complications, and outcomes of
      TT. METHODS: We analyzed Israeli surveys of ACS from 2000 to 2004. RESULTS: In
      these surveys, 5,706 (96%) were discharged alive from hospital. Post-ACS TT and
      DT were 76 patients (1.3%) and 2,661 patients (46.7%), respectively. The TT group
      was older with more prior cardiac disease. During hospitalization, the TT
      patients received more intravenous anticoagulant and antithrombotic agents, and
      had more heart failure, arrhythmias, ischemia, and major bleeding (2.6 vs. 0.6%,
      p=0.03). There were no differences in adjusted 30-day and 6-month mortality
      between the 2 groups. CONCLUSION: TT is feasible among ACS patients who require
      concomitant warfarin treatment.

PMID- 16286734
TI  - Use of proton pump inhibitors: an exploration of the attitudes, knowledge and
      perceptions of general practitioners.
AB  - BACKGROUND/AIM: Proton pump inhibitor (PPI) prescribing is costly. The volume of
      PPI prescription is also increasing, despite little evidence that would justify
      the increase. General practitioners (GPs) are largely responsible for PPI
      prescribing, yet knowledge of their views concerning PPIs which might explain the
      apparent anomaly of prescribing costly drugs without justification is lacking.
      The aim of this study is therefore to investigate how GPs make decisions about
      PPI prescribing. METHOD: Qualitative study design using focus groups of 34 GPs
      and 15 training GPs analysed according to grounded theory principles and use of
      constant comparative analysis. RESULTS: The participants showed agreement about
      the clinical factors potentially relevant to PPI prescribing such as age of
      presentation and endoscopy, issues of Helicobacter pylori eradication and issues
      around malignancy. There was considerable controversy, however, as to how to
      apply those factors in real clinical consultations. GPs in training and academic
      GPs tended to be more conservative; service-based GPs more pragmatic. There was
      agreement about the need to review long-term PPI medication, but controversy
      about whether the conventional 'step-up step-down' approach was realistic in
      practice. Good agreement was apparent about the effectiveness, the cost
      implications, and some of the ethical issues surrounding PPIs, but considerable
      controversy as to how far such factors should influence prescribing of PPIs.
      CONCLUSION: The GPs showed good understanding and knowledge of the issues
      surrounding PPI prescribing. There was considerable controversy as to how such
      knowledge should be translated into practice.

PMID- 16286735
TI  - Kinase inhibitor-induced pustules.

PMID- 16286736
TI  - Have methotrexate-induced liver fibrosis and cirrhosis become rare? A matter for
      reappraisal of routine liver biopsies.

PMID- 16286737
TI  - A new concept: paraviral eruptions.

PMID- 16286738
TI  - Gender-related differences in the physiology of the stratum corneum.
AB  - BACKGROUND: Only few studies on gender-related differences in skin physiology
      have been performed--and they provided conflicting results. OBJECTIVE: In the
      present study, the effect of gender on the physiology of the stratum corneum was
      studied. METHODS: The physiological parameters transepidermal water loss, pH
      value, hydration and sebum content were determined on the flexor forearms of 6
      female and 6 male volunteers. In addition, stratum corneum samples, removed by
      tape stripping, were studied for amount, spectroscopic properties, protein
      content, and mass. RESULTS: The skin of women was characterized by a
      significantly higher pH value (5.6 +/- 0.4) than that of men (4.3 +/- 0.4, p <
      0.05). Protein absorption was the only other parameter significantly dependent on
      gender (p < 0.05). Both effects might be caused by differences in human biology,
      such as hormonal status. CONCLUSION: Therefore, the gender of the volunteers
      should be considered in dermatologic studies.

PMID- 16286739
TI  - Fas ligand reduces viability in primary melanoma short-term cell cultures more
      than in metastatic melanoma short-term cell cultures.
AB  - BACKGROUND: Apoptotic pathway aberrations are reported as important tumor
      progression factors in melanoma. OBJECTIVE: Effect of soluble Fas ligand (sFasL)
      and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on short-term
      cultured melanoma cell viability from different stages of melanoma. RESULTS:
      Recombinant human FasL reduced viability after 18 h in a dose-dependent manner in
      4 of 5 cell cultures from primary tumors and 1 of 9 cell cultures from metastatic
      melanoma (67.5 vs. 96.4%, p = 0.007). DNA fragmentation on flow cytometry
      confirmed apoptosis. Incubation with TRAIL had no effect on melanoma cell
      viability. Immunohistochemistry showed Fas in 3 of 4 primary and in 6 of 7
      metastatic lesions, no FasL in primary lesions, and FasL in 5 of 7 metastatic
      lesions. CONCLUSION: Melanoma short-term cell cultures from primary tumors show
      decreased viability under FasL, but not TRAIL stimulation rather than short-term
      cell cultures derived from metastases.

PMID- 16286740
TI  - Survival of mycosis fungoides in patients in the Southeast of England.
AB  - BACKGROUND: Mycosis fungoides (MF) is the most common skin lymphoma. The
      aetiology of MF remains unknown, and no therapy has to date significantly altered
      patient survival. OBJECTIVE: The present study examines trends in survival of MF
      patients in a well-defined population-based disease group, namely patients
      registered over a 40-year period at the Thames Cancer Registry, Southeast
      England. METHODS: The Thames Cancer Registry is a population-based registry,
      covering a population of approximately 14 million people. Data were taken from
      the Surveillance, Epidemiology and End Results cancer registry programme and the
      National Centre for Health Statistics. The database was used to identify cases of
      MF diagnosed between 1961 and 2000. A total of 985 records were identified, 821
      (83%) of which had complete information on age, sex, year of diagnosis and area
      of residence. The observed and relative survivals of patients diagnosed during
      the periods 1971-1975, 1981-1985 and 1991-1995 were examined over a 5-year period
      of follow-up, using the relsurv Stata program to perform Cox proportional hazard
      analysis. RESULTS: A total of 821 MF eligible patients were available with a
      median follow-up of 4.3 years and a maximum follow-up of 30 years. The overall 5
      year relative survival rate was 80%, and there was marked improvement between
      1971 and 1981. The prognostic factors leading to a significantly poorer survival
      were high age, male sex, the presence of the Sezary syndrome, the use of hormone
      treatment and radiotherapy. CONCLUSIONS: A statistically significantly better
      survival over the last 20 years was found. The prognosis is generally good for
      most patients but not all. The best survival was seen for the female patients
      under 45 years of age without the presence of the Sezary syndrome. This
      difference in survival may be partly due to a difference in the disease stage or
      different treatment, or to both.

PMID- 16286741
TI  - Cetuximab-induced acne.
AB  - BACKGROUND: Cetuximab is a member of a new family of antineoplastic agents that
      inhibit epidermal growth factor receptor (EGFR). These molecules may induce
      acneiform eruptions. In this study, we aimed at evaluating (a) the
      characteristics of acne and (b) whether these acneiform eruptions could be
      improved by classical anti-acne treatments. METHODS: All patients treated with
      cetuximab in a single institution from October 2003 to May 2004 were
      prospectively evaluated. The presence of acne, its severity, need for a treatment
      and response to this treatment were recorded. RESULTS: 13 patients were included:
      11 (85%) developed acneiform eruptions after a mean interval of 10 days. It was
      severe in 4/13 (31%). Comedones were never found and acne involved nonclassical
      sites in 3/11. Antibiotic treatment was given to 4 and local treatment to 2
      patients: it was always efficient. CONCLUSION: Cetuximab-induced acne is
      frequent, differs from classical acne and may be treated effectively with
      classical modalities.

PMID- 16286742
TI  - The association between nuchal nevus flammeus and alopecia areata: a case-control
      study.
AB  - BACKGROUND: The association of alopecia areata (AA) with nuchal nevus flammeus
      (NNF) has been demonstrated by previous studies. OBJECTIVES: The aim of this
      study was to investigate whether AA is associated with NNF. METHODS: 199 AA
      patients and 215 controls without AA were examined for the presence of NNF.
      RESULTS: 35 patients (17.6%) in the AA group had NNF. In the control group, 20
      patients (9.3%) had NNF (odds ratio = 2.08, 95% confidence interval 1.43-2.73; p
      = 0.013). A statistically significant association was found between the presence
      of NNF and duration of the AA (p < 0.001). The presence of NNF was associated
      with severity of AA (p < 0.001). CONCLUSIONS: The results of our study suggest a
      link between NNF and AA especially in severer and more chronic forms.

PMID- 16286743
TI  - Low-dose triamcinolone acetonide in the phytocosmetic lichtena reduces
      inflammation in mild to moderate atopic dermatitis.
AB  - BACKGROUND: Previously, we reported the efficacy of Lichtena--a phytocosmetic
      cream product--in atopic dermatitis (AD). Later, fraudulent triamcinolone
      acetonide (TACA) was detected at low doses (16-40 microg/g) in Lichtena. This
      suggested that TACA may be effective at much lower concentrations than used in
      commercial products (1,000 microg/g). OBJECTIVES: To investigate the efficacy in
      AD of low-dose TACA in Lichtena compared to plain Lichtena. METHODS: Fourteen
      patients presenting symmetrical lesions of AD were treated for 1 month with
      Lichtena plus 25 microg/g TACA (= verum) and plain Lichtena (= placebo). The
      severity of the lesions was assessed by the Severity Scoring of Atopic Dermatitis
      (SCORAD) on days 0 (= baseline), 7, 14 and 28. RESULTS: Already after 1 week of
      treatment, significant SCORAD differences to baseline were observed comparing
      verum- and placebo-treated areas. No improvement was observed using plain
      Lichtena. CONCLUSIONS: TACA displayed a significant improvement of AD at doses up
      to 40 times lower than in commercial products.

PMID- 16286744
TI  - Topical calcineurin inhibitors decrease the production of UVB-induced thymine
      dimers from hairless mouse epidermis.
AB  - BACKGROUND: An increased incidence of ultraviolet-light-related skin tumours is a
      well-known problem in patients undergoing posttransplantation immunosuppression
      with systemic calcineurin inhibitors such as cyclosporine A or tacrolimus. UV
      related carcinogenesis as a consequence of long-term treatment of sun-exposed
      sites with topical calcineurin inhibitors is therefore of theoretical concern.
      RESULTS: In this study, we show that tacrolimus acts as a UVB filter when
      incorporated into liposome membranes. In hairless mice pretreated with 1%
      pimecrolimus cream, 0.1% tacrolimus ointment or vehicle, the amount of epidermal
      thymine dimers, measured 1 h after 1 J/cm2 of UVB irradiation, was decreased by
      89, 84 and 47%, respectively, as compared to untreated mice. Forty-eight hours
      after UVB irradiation, 97, 89 and 93% of epidermal thymine dimer levels were
      removed in pimecrolimus-, tacrolimus- or vehicle-treated mice, respectively. In
      contrast, 69% of thymine dimers, originally present in much higher amounts than
      in treated mice, were removed from untreated controls. UVB-induced apoptosis was
      less pronounced in treated mice. CONCLUSION: Taken together, these results
      suggest that topical calcineurin inhibitors prevent DNA photodamage due to a
      filter effect of both vehicle and active components, whereas they do not affect
      the clearance of DNA photoproducts.

PMID- 16286745
TI  - Skin manifestations of West Nile virus infection.
AB  - West Nile virus (WNV) infection is a potentially lethal arbovirus infection. Many
      notable outbreaks have occurred during the last few years throughout the world,
      including Europe and the USA. The severity of the disease is mainly related to
      the neurological complications. A maculopapular exanthema is reported as a
      clinical sign of the disease. Recently an outbreak of WNV infection occurred in
      southern France. Three patients out of 6 had a similar skin roseola-like
      eruption. The cluster of 3 cases of similar febrile roseola of unexplained cause
      during the same week led to the diagnosis of the first WNV human outbreak in
      France for 40 years.

PMID- 16286747
TI  - A case of amicrobial pustulosis of the folds associated with neutrophilic
      gastrointestinal involvement in systemic lupus erythematosus.
AB  - BACKGROUND: Amicrobial pustulosis of the folds is a recently described entity
      characterized by relapsing pustular lesions involving predominantly the cutaneous
      folds and the scalp. The disease typically occurs in the context of an autoimmune
      or systemic disease and should be included within the spectrum of neutrophilic
      dermatoses. OBSERVATION: We describe a patient with a history of systemic lupus
      erythematosus, who developed amicrobial pustulosis of the folds. Strikingly, the
      patient also exhibited recurrent oral and gastrointestinal manifestations that
      paralleled the course of the cutaneous signs. CONCLUSIONS: Our observation
      indicates that, in analogy to the other neutrophilic dermatoses, amicrobial
      pustulosis of the folds can also be complicated by the development of
      extracutaneous neutrophilic involvement, knowledge of which is critical for its
      diagnosis and proper management.

PMID- 16286746
TI  - Successful treatment of acrodermatitis continua of Hallopeau with sequential
      combination of calcipotriol and tacrolimus ointments.
AB  - Acrodermatitis continua of Hallopeau (ACH) is a rare type of pustular psoriasis
      affecting the digits. We report on a 43-year-old female patient who had been
      suffering from ACH for more than 20 years. Despite the fact that the disease was
      localized on one finger during the whole period, several topical and systemic
      treatments resulted in only temporary or partial improvement of the lesion.
      Although the monotherapies with calcipotriol and tacrolimus ointments gave no
      satisfying results in the long-term management of the disease, the combination of
      both agents led to a continuous improvement of the patient's skin condition.

PMID- 16286748
TI  - Topical methimazole as a new treatment for postinflammatory hyperpigmentation:
      report of the first case.
AB  - We have previously shown that the peroxidase inhibitor methimazole (1-methyl-2
      mercapto imidazole; MMI) is a noncytotoxic inhibitor of melanin production in
      cultured B16 melanocytes. It was further demonstrated that the topical
      application of 5% MMI on brown guinea pig skin for 6 weeks causes a significant
      reduction in the amount of epidermal melanin, resulting in visually recognizable
      cutaneous depigmentation. Herein, we report a 27-year-old male with
      postinflammatory hyperpigmentation (due to acid burn), successfully treated with
      topical MMI as a new skin depigmenting agent. Topical 5% MMI caused a moderate to
      marked improvement of the hyperpigmented lesions within 6 weeks of once-daily
      application. Topical MMI was well tolerated by the patient and did not affect the
      level of serum thyroid hormones (free thyroxin, free triiodothyronine and the
      thyroid-stimulating hormone). Unlike most known depigmenting agents, such as
      hydroquinone and kojic acid, MMI is a noncytotoxic, nonmutagenic compound, and it
      is possible that MMI could serve as a novel agent for the treatment of
      hyperpigmentary disorders in human.

PMID- 16286749
TI  - Severe pustular eruption associated with imatinib and voriconazole in a patient
      with chronic myeloid leukemia.
AB  - Imatinib is a specific and potent inhibitor of the BCR-ABL tyrosine kinase.
      Several clinical trials have demonstrated the efficacy of imatinib in chronic
      myeloid leukemia. Adverse cutaneous reactions induced by imatinib are frequent
      and may be dose related. We report a case of an unusual pustular eruption in a
      patient with chronic myeloid leukemia, who received high doses imatinib for blast
      crisis and later voriconazole for invasive pulmonary aspergillosis. At the time
      of his skin eruption, elevated plasma levels of imatinib were recorded. Imatinib
      is primarily metabolized by the cytochrome CYP3A4. Voriconazole is a cytochrome
      CYP3A4 inhibitor and can lead to high plasma levels of imatinib. This case
      suggests that severe drug reactions to imatinib may be related not only to
      imatinib doses, but also to elevated plasma drug levels resulting from
      pharmacokinetic interactions. The monitoring of imatinib plasma levels may be of
      help for identifying patients at risk for severe toxicity.

PMID- 16286750
TI  - Sirolimus-induced acneiform eruption.
AB  - Sirolimus is a new immunosuppressive agent used to prevent rejection in renal
      allograft recipients in order to reduce the need of potentially nephrotoxic
      calcineurin inhibitors (cyclosporine, tacrolimus). The cutaneous side effects of
      sirolimus are not well known and they may have been underestimated. We report 2
      cases of follicular acneiform eruptions induced by sirolimus in renal allograft
      recipients. This dermatologic complication was severe and difficult to treat, and
      resolved only after discontinuation of sirolimus.

PMID- 16286751
TI  - Topical immunotherapy with diphenylcyclopropenone in combination with DTIC and
      radiation for cutaneous metastases of melanoma.

PMID- 16286752
TI  - Pemphigus vulgaris with no mucosal lesions showing pemphigus-foliaceus-like skin
      manifestations: Is there a 'cutaneous type' of pemphigus vulgaris?

PMID- 16286753
TI  - Follicular drug eruption induced by gefitinib (ZD 1839, iressa): clinical picture
      correlates with in vitro data of focal epidermal necrosis after epidermal growth
      factor inhibition in skin cultures.

PMID- 16286754
TI  - Non-pigmented micromastocytomas: an exceptional presentation of cutaneous
      mastocytosis in an adult.

PMID- 16286755
TI  - Uncommon localization of calcinosis cutis after liver transplantation.

PMID- 16286756
TI  - Topical khellin and natural sunlight in the outpatient treatment of recalcitrant
      palmoplantar pompholyx: report of an open pilot study.

PMID- 16286757
TI  - Intra-areolar polythelia with a partly doubled areola without any other
      malformation of the breast.

PMID- 16286758
TI  - Rectal bleeding following acitretin therapy for discoid lupus erythematosus.

PMID- 16286759
TI  - Poikiloderma of civatte and rosacea: variants in the same nosological spectrum?

PMID- 16286760
TI  - Childhood dermatosis due to microchimerism.

PMID- 16286762
TI  - How robust are laboratory measures of growth hormone status?
AB  - Biochemical assessment of growth hormone (GH) status is required in both
      suspected GH deficiency and GH excess. GH secretion can either be measured
      through investigation of the pituitary or by monitoring markers that change as a
      consequence of GH action on its target tissues. The two most widely used and, to
      date, best validated biochemical parameters are immunoassay measurement of either
      human GH (hGH) or insulin-like growth factor (IGF)-I. The fundamental difference
      between measurement of hGH and IGF-I is that the first reflects GH secretion
      while the second reflects GH action. However, because GH secretion is pulsatile
      in nature, random blood sampling for determination of hGH levels is only
      minimally informative. Analytical methods for measuring GH and IGF-I show
      considerable between-method variability. Since these parameters are used in
      establishing diagnoses and in monitoring GH-related diseases, the endocrinologist
      should be aware of the specifications and limitations of the analytical methods
      available.

PMID- 16286763
TI  - A nationwide attempt to standardize growth hormone assays.
AB  - The Growth Hormone (GH) and Its Related Factors Study Committee of the Foundation
      for Growth Science, Japan, has been conducting a quality control study for 15
      years to improve the equality of diagnosis of GH deficiency. It found that the
      greatest differences in measured GH values were due to the different potencies of
      the kit standards, which were primarily adjusted to WHO standards for human GH of
      pituitary origin. With the collaboration of kit makers and the Study Group of
      Hypothalamo-Pituitary Disorders of the Ministry of Health, Labor and Welfare, all
      GH kits in Japan have begun using the same recombinant human GH standard since
      April 2005. As a result the diagnostic cut-off peak GH has changed from 10 to 6
      ng/ml.

PMID- 16286764
TI  - The phenotype of adults with partial growth hormone deficiency.
AB  - The concept of partial growth hormone (GH) deficiency (GHD) is well established
      within the paediatric setting having been validated against height velocity. In
      hypopituitary adults, GHD is defined by a peak GH response <3 microg/l to
      stimulation. This cut-off is arbitrary due to the lack of a biological marker
      equivalent of height velocity. The majority of normal adults achieve peak GH
      levels several fold higher than this cut off during stimulation. It can be
      argued, therefore, that there is a cohort of hypopituitary adults with
      intermediate peak GH values (3-7 microg/l), who have relatively impaired GH
      secretion, and for whom the impact of this partial GHD (GH insufficiency, GHI) on
      biological endpoints is not known. Studies of GHI adults have demonstrated an
      abnormal body composition, adverse lipid profile, impaired cardiac performance,
      reduced exercise tolerance and insulin resistance. The severity of these
      abnormalities lies between GHD adults and normal subjects. Whether these
      anomalies translate into increased mortality, as observed in GHD hypopituitary
      adults, is not yet known. Given the presence of similar sequelae in GHI and GHD
      adults, and the improvements during GH replacement in GHD adults, a randomized
      placebo-controlled study of GH replacement in GHI patients is warranted.

PMID- 16286766
TI  - Does surgical genitoplasty affect gender identity in the intersex infant?
AB  - There is no clear-cut answer to the question of whether surgical genitoplasty
      affects gender identity in the intersex infant. The debate centres around which
      is more important for the development of gender identity: the biological sex of a
      child or the sex in which a child is reared. We believe that the surgical
      achievement of a phenotype concordant with the sex of rearing is a tremendous
      help to the parents of an intersex infant. We do not consider that the 'neutral'
      upbringing of a child with ambiguous genitalia is a feasible option, first
      because of the parents' distress which prevents them from raising their child
      normally and second because in most cultures around the world gender variants are
      not treated as equals. A neutral upbringing may induce psychosocial consequences
      that are more pernicious than carefully considered neonatal sex attribution and
      concordant surgical genitoplasty.

PMID- 16286765
TI  - The basis of gender assignment in disorders of somatosexual differentiation.
AB  - Sex assignment of patients with disorders of somatosexual differentiation is a
      controversial topic. The aim is to enable the patient to develop a stable gender
      identity during childhood, adolescence and adulthood. Enormous advances have
      recently been made in our knowledge of the molecular mechanisms of sexual
      differentiation and it is understood that long-term outcome may depend on the
      underlying diagnosis. There is increasing evidence that genital development is
      dependent on the action of androgenic steroids; moreover, both androgens and
      oestrogens may have an impact on other developing organs including neuronal
      structures such as the brain. Long-term outcome studies on the various
      intersexuality disorders are desperately needed in order to establish a basis for
      evidence-based medicine regarding sex assignment and treatment options. Premature
      decisions leading to irreversible interventions before an accurate diagnosis has
      been established must be avoided.

PMID- 16286767
TI  - Psychological long-term outcome in intersex conditions.
AB  - For decades, sex assignment in children with intersex conditions has depended
      more on surgical possibilities than on other criteria, since it was assumed that
      children are psychosexually neutral at birth. Adults with intersex conditions and
      professionals in the field have increasingly criticized this policy after the
      publication of studies suggesting that prenatal brain exposure to sex hormones
      determines gender development. Although prenatal brain exposure to androgens
      plays some part in the development of gender role behaviour, the current evidence
      is not in line with the idea of determination of gender identity through prenatal
      sex steroid exposure. Recent reviews on gender dysphoria and gender change in
      patients with intersex conditions show that initial gender assignment still seems
      to be the best predictor of adult gender identity.

PMID- 16286768
TI  - Hormone treatment of the adult transsexual patient.
AB  - Hormonal reassignment has two aims: (1) to reduce the hormonally induced
      secondary sex characteristics of the original sex and (2) to induce the secondary
      sex characteristics of the new sex. In Europe, cyproterone acetate is generally
      used to inhibit androgens in male-to-female transsexuals. Medroxyprogesterone
      acetate is an acceptable, though less effective, alternative. To induce
      feminization there is a wide range of oestrogens. Oral ethinyloestradiol is a
      potent and inexpensive oestrogen, but it may cause venous thrombosis. Oral 17beta
      oestradiol valerate or transdermal 17beta-oestradiol is the treatment of choice.
      The goal of treatment in female-to-male transsexuals is to induce virilization,
      including a male pattern of sexual hair, a male voice and male physical contours,
      and to stop menses. The principal hormonal treatment is a testosterone
      preparation. Hormone-dependent tumours have been encountered and surveillance is
      necessary.

PMID- 16286769
TI  - Sex steroids and the growth hormone/insulin-like growth factor-I axis in adults.
AB  - In healthy adults insulin-like growth factor (IGF)-I levels do not differ between
      males and females, whereas spontaneous growth hormone (GH) secretion is
      approximately twofold higher in females. Untreated GH-deficient (GHD) women
      exhibit lower IGF-I levels compared with men and the increase in serum IGF-I
      during GH replacement is also significantly less. These data suggest a resistance
      to GH in women, which in healthy subjects is compensated for by increased GH
      secretion. Administration of oral oestrogen in healthy postmenopausal women
      suppresses hepatic IGF-I production and increases pituitary GH release, and oral
      oestrogen replacement in women with GHD lowers IGF-I concentrations and increases
      the amount of GH necessary to achieve IGF-I target levels during treatment. These
      data clearly suggest that hepatic suppression of IGF-I production by oestrogen
      subserves the gender difference in GH sensitivity, but it is also likely that sex
      steroids may interact with the GH/IGF axis at other levels. There is also
      circumstantial evidence to indicate that testosterone stimulates IGF-I production
      and it is speculated that a certain threshold level of androgens is essential to
      ensure hepatic IGF-I production. Whether these data should translate into earlier
      discontinuation of oestrogen replacement therapy in women with hypopituitarism
      merits consideration.

PMID- 16286770
TI  - Early onset of puberty: tracking genetic and environmental factors.
AB  - Under physiological conditions, factors affecting the genetic control of
      hypothalamic functions are predominant in determining the individual variations
      in timing of pubertal onset. In pathological conditions, however, these
      variations can involve different genetic susceptibility and the interaction of
      environmental factors. The high incidence of precocious puberty in foreign
      children migrating to Belgium and the detection in their plasma of a long-lasting
      1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (DDT) residue suggest the
      potential role of environmental endocrine disrupting chemicals in the early onset
      of puberty. This hypothesis was confirmed by experimental data showing that
      temporary exposure of immature female rats to DDT in vivo results in early onset
      of puberty. We compared the gene expression profile of hypothalamic hamartoma
      associated or not with precocious puberty in order to identify gene networks
      responsible for both hamartoma-dependent sexual precocity and the onset of normal
      human puberty. In conclusion, pathological variations in the timing of puberty
      may provide unique information about the interactions of either environmental
      conditions or genetic susceptibility with the hypothalamic mechanism controlling
      the onset of sexual maturation, as shown by examples of precocious puberty
      following exposure to endocrine disrupters or due to hypothalamic hamartoma.

PMID- 16286771
TI  - Isolated gonadotropic deficiency with and without anosmia: a developmental defect
      or a neuroendocrine regulation abnormality of the gonadotropic axis.
AB  - Hypogonadotropic hypogonadism has been described in several human genetic
      diseases. Congenital isolated hypogonadotropic hypogonadism is classified into
      two categories: one that is associated with anosmia (Kallmann syndrome) and one
      that is apparently isolated. Mutations and deletions of the KAL1 gene, which
      encodes for a protein involved in cell adhesion, have been observed in many cases
      of the X-linked form of Kallmann syndrome. Recently, loss-of-function mutations
      of fibroblast growth factor receptor-1 (FGFR1) were associated with an autosomal
      dominant form of Kallmann syndrome. Genotype-phenotype correlations confirm the
      large spectrum of the phenotype due to FGFR1 mutations. Cases of isolated
      hypogonadotropic hypogonadism were considered to be idiopathic until the
      description of mutations of the gonadotropin releasing hormone receptor,
      luteinizing hormone and follicle stimulating hormone genes. However, defects in
      these genes only account for a small percentage of familial cases, which suggests
      that other proteins may be involved in regulation of the gonadotropic axis. We
      recently described GPR54 as one of these proteins by genome mapping in a very
      informative family. In vivo studies and genotype-phenotype correlations indicate
      that gonadotropic axis regulation by GPR54 occurs mainly at the level of the
      hypothalamus.

PMID- 16286772
TI  - Precocious puberty: growth and genetics.
AB  - The precise neuroendocrine mechanisms underlying activation of hypothalamic
      pituitary-gonadal (HPG) axis maturation are elusive. The wide age range of
      pubertal onset among normal individuals throughout the world may suggest that
      both genetic and environmental factors modulate the timing of puberty. Early
      activation of the HPG axis, termed central precocious puberty (CPP), causes
      psychosocial difficulties and may lead to compromised final height, especially if
      medical intervention is delayed. Although CPP is considered to be idiopathic in
      the majority of patients, we have recently reported a 27.5% prevalence of
      familial cases among 147 patients with idiopathic CPP. Segregation analysis of
      this cohort suggested an autosomal dominant transmission with incomplete sex
      dependent penetrance. Allelic variants of candidate genes that regulate the
      timing of puberty may cause familial CPP. Detection of these genes will provide a
      tool for identification of children at risk of developing CPP, enabling early
      intervention with the aim of preventing its distressing outcomes.

PMID- 16286774
TI  - Treatment of short children born small for gestational age: US perspective, 2005.
AB  - Growth hormone (GH) administration to ameliorate growth deficiency of short
      children born small for gestational age (SGA) is currently approved in the US and
      the EU. Even though regulatory bodies from each examined similar datasets
      concerning GH treatment of short SGA children, the specifics of indications for
      treatment and recommended regimens differed with respect to GH dosage, age at
      which therapy might be initiated, and the degree of short stature required. US
      product labeling allows more flexibility but provides less guidance for the
      practitioner. The EU tends to be more proscriptive, limiting use to shorter
      children, restricting the dosage, and providing specific guidelines in terms of
      monitoring during treatment.

PMID- 16286776
TI  - Congenital adrenal hyperplasia in adulthood: do men need to continue treatment?
AB  - Due to early diagnosis and appropriate paediatric treatment, internists and
      endocrinologists are now caring for an increasing number of adult patients with
      congenital adrenal hyperplasia (CAH). Problems that may be encountered in adult
      males with CAH are the continuing risk of developing an adrenal crisis and
      impaired gonadal function due to suppression of the hypothalamic-gonadal axis.
      Fertility may be further compromised by testicular adrenal rest tumours.
      Available data suggest that the reversal of infertility is more difficult once
      testicular nodules have developed. Similar to female CAH patients, male patients
      may develop adrenal tumours due to inadequate adrenocorticotropic hormone
      suppression. We therefore recommend continuous treatment of male CAH patients
      with careful monitoring of clinical and hormonal parameters in order to avoid
      overtreatment.

PMID- 16286775
TI  - Timing and type of glucocorticoid replacement in adult congenital adrenal
      hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) is one of the commonest inherited diseases.
      Treatment during childhood is directed towards obtaining normal growth. There is
      an extensive literature on management of CAH during childhood but little
      published on how patients should be treated as adults. CAH results in increased
      adrenocorticotropic hormone levels driving the adrenal to produce cortisol and
      thereby excessive cortisol precursors which are predominantly androgenic. In
      normal individuals there is a marked circadian rhythm in cortisol release with
      the lowest levels occurring shortly after midnight and rising between 02.00 and
      03.00 h to peak at around 06.00-08.00 h after waking. The treatment of choice for
      children with CAH is hydrocortisone three times daily. There is no consensus on
      treating adults. A recent survey by the UK Society for Endocrinology showed that
      hydrocortisone was the most popular steroid, followed by dexamethasone and then
      prednisolone. Sixty percent of respondents used a reverse circadian pattern of
      glucocorticoid treatment and only 16% used a dose based on weight or surface
      area. In a recent study we demonstrated that the most important variable
      determining hydrocortisone bioavailability is weight and we advocated a weight
      related dosing regimen monitored using a nomogram for serum cortisol. .

PMID- 16286777
TI  - Difficulties in patient management associated with the transition period.
AB  - The European Society for Paediatric Endocrinology (ESPE) held a consensus
      workshop in Manchester, UK, in December 2003 to discuss issues relating to the
      care of growth hormone (GH)-treated patients in the transition from paediatric to
      adult life. Aspects under consideration included the definition of transition,
      the process of delivery of transitional care, the exact need to reassess
      pituitary status after completion of growth and puberty in teenagers who have
      received GH treatment during childhood, the most appropriate biochemical
      definition of severe GH deficiency (GHD) in the transitional period, and the
      factors influencing both the decision to reinstitute treatment and also the
      timing and dosage schedule when GH treatment is reinstituted.

PMID- 16286778
TI  - Management of bone health in postmenopausal women.
AB  - Osteoporosis is a major public health problem. We now have an approach to case
      finding that involves the measurement of bone mineral density in people at high
      risk of fractures. The management of the individual includes the identification
      of risk factors, the choice of optimal therapy and the encouragement of long-term
      adherence with the planned treatment. The drugs that are available for the
      prevention of fractures are classed as anticatabolic or anabolic. The efficacy of
      these agents can be evaluated in the individual by monitoring changes in bone
      mineral density or bone turnover markers.

PMID- 16286779
TI  - The role of parathyroid hormone in the management of osteoporosis.
AB  - It has been over 2 years since parathyroid hormone (PTH 1-34) was approved in the
      US and Europe for the treatment of osteoporosis in postmenopausal women and men.
      Clinical experience with this peptide has enhanced confidence in its use and its
      application in specific clinical scenarios. There is no doubt that PTH 1-34 is
      safe and effective in reducing spine and non-vertebral fractures in men and
      women. However, the lack of several randomized placebo-controlled trials and
      their relatively short duration raise several questions that still need to be
      answered. This paper reviews three major areas of uncertainty: (1) Is there
      significant heterogeneity in the bone density response of individuals to PTH? If
      so, what factors are important predictors? (2) What other regimens are available
      for PTH use? (3) What, if anything, should the clinician do after PTH is
      discontinued? Answers to these questions will undoubtedly lead to even greater
      utilization of this drug and some of its future derivatives.

PMID- 16286781
TI  - Hormonal regulation of growth plate cartilage.
AB  - Longitudinal bone growth occurs in the growth plate through a process called
      endochondral bone formation, a process where resting zone chondrocytes are
      recruited to start active proliferation and then undergo differentiation,
      followed by apoptosis and later mineralization. The balance between proliferation
      and differentiation is a crucial regulatory step controlled by various growth
      factors/hormones acting in both endocrine and paracrine/autocrine ways. From
      studies of individuals with aromatase deficiency and a boy with defective
      oestrogen receptor (ER)-alpha it has become clear that oestrogen action is
      indispensable for normal pubertal growth and growth plate fusion. Both oestrogen
      receptors, ER-alpha and ER-beta, are expressed in the growth plate in boys and
      girls throughout pubertal development. Any functional role of ER-beta has not yet
      been defined in the human growth plate. Increased understanding about the effects
      of oestrogen and the interactions between oestrogens and other endocrine factors
      within the growth plate is important for the development of new treatment
      strategies in different disorders affecting longitudinal bone growth. As new
      specific modulators of oestrogen receptors are developed, these could offer more
      specific ways to modulate longitudinal growth and growth plate fusion.

PMID- 16286780
TI  - Turner syndrome in adulthood.
AB  - Turner syndrome is a common genetic disorder associated with abnormalities of the
      X chromosome and occurs in about 50 per 100,000 liveborn girls. It is associated
      with reduced adult height, gonadal dysgenesis and thus insufficient circulating
      levels of female sex steroids and infertility. Morbidity and mortality are
      increased throughout the lifespan. The average intellectual performance is within
      the normal range. A number of recent clinical studies have given new insight
      particularly into the adult phase of Turner syndrome. Treatment with growth
      hormone during childhood and adolescence enables a considerable gain in adult
      height. In most cases puberty has to be induced and female sex hormone
      replacement therapy is given during adulthood. Type 2 diabetes is often seen, and
      hypertension and associated cardiovascular disorders are frequent. The proper
      treatments of these disorders have not been firmly established. Since the risk of
      cardiovascular and endocrinological disease is clearly elevated, proper care
      during adulthood is crucial. Cognition and social functioning are altered in
      Turner syndrome.

PMID- 16286782
TI  - Resurrections in Toronto: the emergence of insulin.
AB  - The discovery of insulin remains the greatest and one of the most controversial
      events in the history of endocrinology. Hypotheses about the possible existence
      of an internal secretion of the pancreas date from the early 1890s and were
      steadily modified with the development of the concept of an endocrine system. In
      the spring of 1922, after many false starts and dead ends, a team of researchers
      at the University of Toronto provided conclusive evidence of the existence of the
      internal secretion of insulin. The discovery process was fraught with personal
      and scientific rivalries more striking than fiction. The early use of insulin on
      starved, dying diabetic children awed everyone involved in the process. With the
      discovery of insulin, endocrinology moved into the mainstream of medical science.

PMID- 16286783
TI  - Cilostazol, an inhibitor of type 3 phosphodiesterase, produces endothelium
      independent vasodilation in pressurized rabbit cerebral penetrating arterioles.
AB  - We investigated the effects of cilostazol, a potent inhibitor of cGMP-inhibited
      cAMP phosphodiesterase, on mechanical activity of isolated pressurized rabbit
      cerebral penetrating arterioles with special reference to the function of the
      endothelium. Both cilostazol and milrinone, another inhibitor of cAMP
      phosphodiesterase, produced vasodilation of the cerebral penetrating arterioles
      in a dose-dependent manner. Pretreatment with selective inhibitors of
      cyclooxygenase or nitric oxide synthase, or chemical denudation of the
      endothelial cells caused no significant effect on the cilostazol-mediated
      vasodilation of the cerebral arterioles. A selective large-conductance calcium
      activated potassium channel inhibitor, iberiotoxin, and a selective protein
      kinase A inhibitor, H-89, caused no significant effect on the cilostazol-mediated
      vasodilation. In the cerebral arterioles, low concentration (10(-6)M) of
      cilostazol or milrinone caused a significant shift of the dose-vasodilatory
      response curve for adenosine to the left. These findings suggest that cilostazol
      produces vasodilation independent of the presence of the endothelium or
      activation of endogenous vasodilative prostaglandins, nitric oxide, calcium
      activated potassium channel and protein kinase A. In conclusion, the vasodilator
      action of cilostazol may, in part, contribute to the beneficial effect of
      preventing lacunar cerebral infarction in patients with functional damage of the
      endothelium in cerebral penetrating arterioles.

PMID- 16286784
TI  - Mycophenolate mofetil in anti-neutrophil cytoplasm antibodies-associated systemic
      vasculitis.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) is an immune suppressive initially
      introduced for the prevention of solid organ allograft rejection that is
      increasingly used in autoimmune conditions, including vasculitis. METHODS: This
      retrospective study evaluated the efficacy and tolerability of MMF in 51
      sequential patients with anti-neutrophil cytoplasm antibodies-associated systemic
      vasculitis (AASV) treated in a single centre between 2001 and 2004. RESULTS: The
      mean age was 54 years and median disease duration was 36 months. A mean of 3.5
      systems were involved and the previous median exposure to cyclophosphamide was 9
      g. MMF was administered either as remission maintenance therapy (29/51, 56.9%) or
      as treatment for active disease (22/51, 43.1%). The mean duration of MMF therapy
      was 20 months and the mean MMF dose during the first year was 1.6 g/day. 14/29
      (48.3%) of those receiving MMF for remission maintenance therapy eventually
      relapsed with a mean time to relapse of 14 months. Of those receiving MMF for
      relapsing disease, 3 failed to respond to therapy while the rest achieved
      remission by 3.9 months. However, 9 of these subsequently flared; mean time to
      disease flare was also 14 months. MMF was withdrawn in 28 patients (54.9%)
      because of treatment inefficacy in 21, severe adverse events in 5 and intolerance
      in 2. Of the 51 treated, 36 (70.6%) experienced at least 1 side effect, namely
      infections in 24, gastrointestinal side effects in 12 and psychological events in
      6 patients. CONCLUSIONS: We have observed varying efficacy of MMF in AASV, with
      over 50% of patients with relapsing disease achieving remission and marked falls
      in concomitant steroid doses. However, longer follow-up indicates a subsequent
      relapse rate of over 50% that may be associated with low MMF dosing.

PMID- 16286785
TI  - Serum levels of 1-84 and 7-84 parathyroid hormone in predialysis patients with
      chronic renal failure measured by the intact and bio-PTH assay.
AB  - BACKGROUND: The intact parathyroid hormone (PTH) assay detects both PTH(1-84) and
      the PTH(7-84)-like fragment, which is reported to be an antagonist of the
      biological action of PTH(1-84). It is debatable which of the two assays is
      clinically more useful, the intact or bio-PTH assay, the latter of which only
      detects PTH(1-84). It is also unknown whether serum levels of the PTH(7-84)-like
      fragment have clinical significance. METHODS: Serum PTH concentrations in 104
      predialysis patients with chronic renal failure (CRF; serum creatinine 3.53 +/-
      1.93; 62 males and 42 females; 61.0 +/- 11.5 years old) were measured using both
      the intact and bio-PTH assays, and the concentration of the PTH(7-84)-like
      fragment was calculated by subtracting bio-PTH from intact PTH. Three bone
      formation and three bone resorption markers were measured simultaneously.
      RESULTS: The PTH values measured using the two assays were strongly positively
      correlated (r = 0.959, p < 0.0001), and were also significantly positively
      correlated with the three bone formation and three bone resorption markers to a
      similar degree. The PTH(7-84)-like fragment was significantly positively
      correlated with both the intact and bio-PTH (r = 0.855, p < 0.0001 for intact
      PTH; r = 0.672, p < 0.0001 for bio-PTH), and was also significantly positively
      correlated with each of the six bone metabolism markers. There is no significant
      relationship between the bio-PTH/PTH(7-84)-like fragment ratio and clinical
      parameters including bone metabolic markers. CONCLUSION: From the strong
      relationship between the two assays, and the similar degree of the relationship
      between each PTH assay and each of the six bone metabolism markers, it is
      considered that the bio-PTH and intact PTH assays have similar clinical
      significance in predialysis CRF patients. Serum levels of the PTH(7-84)-like
      fragment seem to increase as serum PTH(1-84) increases. The results suggest that
      the serum PTH(7-84)-like fragment has little specific clinical effect on bone
      metabolism, even when assessed by the ratio of bio-PTH/PTH(7-84)-like fragment.

PMID- 16286786
TI  - Organ-specific collagen expression: implications for renal disease.
AB  - Chronic kidney disease is characterized by progressive accumulation of
      extracellular matrix and scarring, leading to the loss of kidney function. Excess
      deposition of the collagen family of proteins is the hallmark of kidney fibrosis.
      In this review, we survey the collagens that are associated with renal disease
      and we highlight the use of a transgenic approach to identify cis-acting
      sequences in the collagen type I promoter which are capable of directing collagen
      type I expression specifically in the kidney. Ultimately it may be possible to
      use this approach to halt the accumulation of collagen selectively in this organ.

PMID- 16286787
TI  - Effect of trimethoprim-sulfamethoxazole on Na and K+ transport properties in the
      rabbit cortical collecting duct perfused in vitro.
AB  - BACKGROUND: In this study, the membrane mechanisms of hyperkalemia caused by
      trimethoprim-sulfamethoxazole (TMP-SMX) combination antibiotics were assessed in
      the cortical collecting duct (CCD). METHODS: We used the microelectrode technique
      and flux measurements, and examined the effects of TMP and SMX on electrical
      properties of the apical and basolateral membranes in the rabbit CCD perfused in
      vitro. RESULTS: TMP in the lumen caused increases in apical membrane voltage,
      fractional apical membrane resistance (fRA), and transepithelial resistance (RT),
      all effects which were completely inhibited by luminal amiloride, but not by
      luminal Ba2+. The luminal TMP inhibited both net Na+ reabsorption and K+
      secretion in the CCD. TMP in the bath slightly but significantly depolarized
      transepithelial voltage and basolateral membrane voltage without influencing fRA
      or RT. SMX in the lumen or bath had no effect on barrier voltages or resistances.
      CONCLUSION: TMP mainly acts on the apical membrane of the CCD, inhibits the
      amiloride-sensitive macroscopic Na+ conductance in this membrane, and thereby
      decreases the net driving force for K+ exit across the membrane, resulting in an
      inhibition of K+ secretion. SMX in the lumen or bath had no effect on the CCD.

PMID- 16286789
TI  - Therapeutic strategies for normal-tension glaucoma.
AB  - Treatment of normal-tension glaucoma has been a subject of debate for several
      years. Glaucomatous damage cannot be influenced directly, and current treatment
      modalities in normal-tension glaucoma are aimed at the control of risk factors.
      Intraocular pressure is a widely accepted risk factor and its reduction can
      improve the prognosis in normal-tension glaucoma patients. The repeated
      demonstration of the importance of hemodynamic factors in normal-tension glaucoma
      has, however, not been paralleled by a comparable progress in the development of
      therapeutic modalities capable of influencing favorably ocular blood flow. Today,
      calcium channel blockers seem to be the most promising adjunctive treatment to be
      considered in patients with glaucomatous optic neuropathy without increased
      intraocular pressure.

PMID- 16286788
TI  - Effect of nitric oxide on ammoniagenesis in rats.
AB  - AIM: This in vitro study using rat cortical slices, isolated proximal tubules and
      mitochondria was conducted to investigate the effect of exogenous and endogenous
      nitric oxide on ammoniagenesis. METHODS AND RESULTS: The cortical slices were
      incubated with phosphate-buffered saline containing 1 mML-glutamine at 37 degrees
      C andglutamine-stimulated ammoniagenesis which was further elevated with 10(-7)M
      ANGII showed a time-dependent decrease during 2 h. 10(-4)M L-NAME or 10(-5)ML
      canavanin caused a similar ammonia elevation to that of ANGII, whereas the
      addition of 10(-5)M SNAP attenuated the ammonia-increasing effects of ANGII and L
      NAME. Basal or exogenous NO without significantly affecting glutamine uptake of
      the slices seemed to convert the glutamine deamidation pathway to transamination,
      since L-NAME increased the ammonia to glutamine ratio from 0.87 +/- 0.08 mol/mol
      to 1.03 +/- 0.04 (p < 0.01). L-NAME increased both ammoniagenesis and
      mitochondrial oxygen consumption but SNAP depressed them. Endogenous NO reduced
      ammoniagenesis without changing the mitochondrial permeability transition pore
      (PTP), whereas exogenous NO-induced attenuation in ammoniagenesis was associated
      with elevated PTP in a CsA-sensitive manner. CONCLUSION: These results
      demonstrated that in rat kidney, basal NO depresses mitochondrial oxygen
      consumption and attenuates ammoniagenesis without affecting PTP; however,
      exogenous NO inhibits ammonia production by disturbing PTP in isolated
      mitochondria.

PMID- 16286790
TI  - Studies on corneal wound healing. Effect of fucose on iodine vapor-burnt rabbit
      corneas.
AB  - Corneal wound healing often leads to the development of scar tissue with loss of
      transparency. Reconstitution of transparent corneal stroma depends on the
      regulation of the biosynthetic activities of postlesional keratocytes and also to
      a large extent on the limitation of matrix degradation, attributed essentially to
      the upregulation of matrix metalloproteases and especially MMP-9. Using a
      standardized method for the production of reproducible corneal lesions by burning
      with iodine vapors, we could show that the local application of 0.5 mg/ml L
      fucose reduced significantly MMP-9 upregulation and accelerated the recovery of
      the epithelial layer of the cornea. The iodine vapor used in the experiments
      produces a rapid loss of epithelium with no or slight effect below the basement
      membrane. A relatively rapid regrowth of epithelium was observed. The speed of
      this reepithelialization was stimulated by the local application of fucose. At 48
      h after burn, there was a difference between fucose-treated and control corneas
      (epithelial thickness was about 50 mum for fucose-treated corneas and 37 microm
      for control corneas). Culture media of in vivo fucose-treated corneas showed an
      important decrease of MMP-9 activity (-51%, n = 6, p < 0.01). It appears that the
      in vivo fucose treatment reduced the MMP-9 activity released in the media. This
      effect is significant 24 h after iodine vapor burn. In order to study the effect
      of fucose on normal corneas, it was added to rabbit as well as human cornea
      explant cultures, and the production and release of MMP-9 was determined by
      zymography. Fucose at a concentration of 0.5 mg/ml produced a 70% decrease of MMP
      9 activity released in the medium by corneal explant cultures. Other mono- and
      oligosaccharides were also tested. Besides lactose, fucose-rich oligosaccharides
      also produced significant inhibition. Galactose, melibiose, mannose and glucose
      were inactive. These results justify the use of fucose for the local treatment of
      corneal wounds.

PMID- 16286791
TI  - Evaluation of arterial stiffness in patients with branch retinal vein occlusion.
AB  - PURPOSE: To assess the arterial stiffness in patients with branch retinal vein
      occlusion (BRVO). METHODS: Brachial-ankle pulse wave velocity (PWV) and ankle
      brachial index were measured in 10 patients with BRVO (mean age 67.9 +/- 7.5
      years) and in 18 age-matched controls (mean age 66.9 +/- 6.8 years). The controls
      were subjects with systemic essential hypertension having no retinal lesions.
      RESULTS: The PWV in the BRVO group was 1,946 +/- 254 cm/s which was significantly
      higher than that in the control group (1,688 +/- 274 cm/s; p = 0.014, Wilcoxon
      rank sum test). The ankle-brachial indexes were 1.16 and 1.15 in BRVO and control
      groups, respectively. There was no significant difference between the groups (p =
      0.944). In the control group, there was a significant positive correlation
      between PWV and systolic blood pressure (Spearman correlation coefficient r(s) =
      0.385, p = 0.043), while no significant correlation was found in the BRVO group
      (Spearman correlation coefficient r(s) = -0.188, p = 0.603). CONCLUSION: The
      arterial stiffness is increased in patients with BRVO which was thought to be due
      to the structural changes of the artery and not dependent on the blood pressure.

PMID- 16286792
TI  - Trypan-blue- and endoillumination-assisted phacoemulsification in eyes with
      vitreous hemorrhage during combined cataract and vitreous surgery.
AB  - PURPOSE: To study the safety and usefulness of trypan blue application and
      conventional endoillumination for enhancing visualization during
      phacoemulsification and foldable intraocular lens implantation in cases of
      cataract with vitreous hemorrhage. METHODS: Ten eyes of 10 patients with cataract
      and coexisting vitreous hemorrhage underwent combined trypan-blue- and
      endoillumination-assisted phacoemulsification and foldable intraocular lens
      implantation with vitrectomy. In a two-step surgery, after staining the anterior
      capsule with trypan blue, continuous circular capsulorhexis was performed; then,
      phacoemulsification was performed using conventional endoillumination. Specular
      microscopy was performed before and 3 months after surgery on eyes that underwent
      trypan-blue- and endoillumination-assisted phacoemulsification and on control
      eyes that underwent standard phacoemulsification to evaluate the toxic effect of
      trypan blue on corneal endothelial cells. RESULTS: Trypan blue application
      improved visualization of the anterior capsule, and a complete capsulorhexis
      could be performed in all eyes. In all 10 eyes, endoillumination was required to
      visualize the lens structure, and phacoemulsification could be accomplished.
      Specular microscopy revealed that there was no significant difference in the
      level of corneal endothelial cell loss between the trypan-blue- and
      endoillumination-assisted phacoemulsification group and the control group.
      CONCLUSION: The described double visualization technique may assist
      phacoemulsification in selected cases of cataract with vitreous hemorrhage.

PMID- 16286793
TI  - Is homelessness a risk factor for eye disease? Results of a German screening
      study.
AB  - BACKGROUND: There is general agreement on the presence of a correlation between
      poverty and impaired health. However, only scarce data are available on whether
      this also applies to the incidence of eye disease. The present study was carried
      out to evaluate the prevalence of ocular disease in homeless people in Germany.
      METHODS: 107 homeless people (97 male, 10 female; mean age 49 years, range 18-81
      years) treated in specialised social service institutions were investigated
      prospectively according to a standardised ophthalmological screening protocol.
      This comprised visual acuity, assessment of pupillary light reaction, intra
      ocular pressure, slit lamp examination as well as funduscopy. RESULTS: The median
      best-corrected visual acuity of all 213 eyes examined was 0.8 (range: no light
      perception to 1.25). 74 eyes of a subgroup of 50 patients showed one or more of
      the following disorders: 32% of the patients suffered from external eye disease,
      8% exhibited a cataract associated with a visual acuity of 0.63 or below. 6% of
      the patients had optic nerve atrophy, and 4% suffered from amblyopia. Diabetic
      retinopathy as well as age-related macular degeneration were detected in 2%,
      while anophthalmos, lid malposition and traumatic choroidal rupture were noted in
      1% of patients. The median visual acuity measured in these 74 eyes was 0.5
      (range: no light perception to 1.25), which differs significantly from the acuity
      of 0.8 in the entire study population (p < 0.001). The prevalence of legal
      blindness according to WHO criteria was 2%. CONCLUSIONS: The present study
      revealed an unexpectedly high prevalence of optic nerve atrophy in homeless
      people. The prevalence for cataract and legal blindness was slightly higher than
      in representative epidemiological investigations. Thus, homelessness seems to be
      correlated with an increased ocular morbidity. As best-corrected visual acuity
      differed significantly between eyes with and those without eye disease, the
      assessment of this parameter may serve as a cost-effective first-stage screening
      method.

PMID- 16286794
TI  - Autofluorescence and angiographic findings of retinal astrocytic hamartomas in
      tuberous sclerosis.
AB  - OBJECTIVE: To describe fundus autofluorescence (AF), fluorescein angiography (FA)
      and indocyanine green angiography (ICGA) in different types of retinal astrocytic
      hamartomas in tuberous sclerosis (Morbus Bourneville-Pringle). METHODS: Two eyes
      with 8 lesions, i.e. type 1 (n = 7) and type 3 (n = 1), were examined. AF
      pictures were taken prior to injection, FA and ICGA images were obtained in the
      early and the late phase. To achieve additional cases, a systematic literature
      review with exten- sive Internet and library search was performed. RESULTS:
      Strong AF was seen in type 2 and type 3 retinal astrocytic hamartomas, whereas
      type 1 lesions blocked the physiologic fundus AF. Fluorescence angiography of all
      types of lesions revealed hypofluorescence in early frames and hyperfluorescence
      originating from leakage in late frames. ICGA showed a subtle blockade in type 1,
      a total blockade in type 2 and in the central part and a partial blockade in the
      peripheral part in type 3 lesions. CONCLUSIONS: Retinal astrocytic hamartomas in
      tuberous sclerosis can be easily detected by angiography, especially type 1
      lesions which are difficult to visualize by funduscopy. Early- and late-phase
      fluorescein angiography and ICGA are helpful to differentiate the three lesion
      types.

PMID- 16286795
TI  - Episcleral venous pressure in untreated primary open-angle and normal-tension
      glaucoma.
AB  - The aim of this prospective study was to investigate episcleral venous pressure
      (EVP) in different forms of glaucoma in comparison with age-matched controls. EVP
      was measured by means of a venomanometer in 32 eyes with untreated primary open
      angle glaucoma (POAG), 36 eyes with untreated normal-tension glaucoma (NTG) as
      well as 56 control eyes without ophthalmological disease other than cataract. In
      addition to ophthalmological standard examination, cardiovascular parameters such
      as systolic and diastolic blood pressure and heart rate were recorded. In the
      POAG group, EVP was 12.1 +/-0.5 mm Hg and in the NTG group 11.6 +/- 0.4 mm Hg.
      This was significantly different from EVP of the controls (9.5 +/- 0.2 mm Hg).
      The EVP/intraocular pressure (IOP) ratio was significantly different in NTG
      patients (80.0% +/- 3.2) in comparison with both POAG patients (67.1% +/- 2.8)
      and controls (69.2% +/- 2.4). The difference between IOP and EVP (IOP - EVP) was
      6.2 +/- 0.6 in the POAG, 3.1 +/- 0.45 in the NTG and 4.5 +/- 0.4 in the control
      group. All these values were significantly different from each other. Regression
      analysis revealed a significant linear correlation between EVP and IOP in both
      the NTG and the POAG group. In the control group, however, the correlation was
      weak. This study is the first to demonstrate differences in EVP between untreated
      NTG and POAG and an age-matched healthy control group.

PMID- 16286796
TI  - Investigation of the safety of an intraocular lens with reversibly adjustable
      optical power: the *Acri.Tec AR-1 PC/IOL.
AB  - PURPOSE: To report the safety of a newly developed intraocular lens (PC/IOL) with
      reversibly adjustable refractive power (*Acri.Tec AR-1 PC/IOL) after implantation
      into adult human eyes. The surgical setup and specially designed instruments
      required for implantation will be evaluated. The examined parameters included:
      stability of the IOL during implantation, positioning of the IOL, rotation of the
      IOL, integrity of the posterior lens capsule, central visual acuity, morphology
      of the eye, clinical signs of inflammation, intraocular pressure, refraction.
      METHODS: The study was carried out on 35 human eyes after using the Acri.Tec AR-1
      PC/IOL after lens removal through phacoemulsification; as control, the
      implantation of conventional PC/IOL into the second eye of 29 patients was used.
      The mean follow-up was 9 + 6 months. An initial adjustment surgery of the
      *Acri.Tec AR-1 PC/IOL was carried out 2 weeks after implantation in 2 patients;
      the follow-up of these eyes was 3 and 6 months. RESULTS: Implantation was
      possible without any problem. Eyes healed normally. No difference between eyes
      containing the *Acri.Tec AR-1 PC/IOL and eyes containing conventional PC/IOLs
      could be detected with respect to visual acuity, stabilization of refractive
      error, signs of inflammatory reaction, slitlamp microscopic aspect of the eye and
      intraocular pressure. As intended, initial adjustment surgery successfully
      changed the mydriatic refraction from +1.0 resp. +0.75 dpt to 0 resp. -0.5 dpt.
      26 bilaterally pseudophakic patients including 2 patients having had adjustment
      surgery had more than 3 months follow-up. Mean visual acuity in the AR-1 PC/IOL
      group at 3 months (0.76 +/-0.24) did not differ from mean visual acuity in the
      pseudophakic control group (0.74 +/-0.23). Adjusted eyes had a visual acuity of
      1.0. No adverse effects occurred. CONCLUSION: Initial data suggest that the
      *Acri.Tec AR-1 PC/IOL can be safely implanted into the capsular bag of adult
      human eyes and can beadjusted after implantation, thereby achieving the desired
      change of refraction. Further exploration of the potential usefulness of this
      type of reversibly adjustable PC/IOL as a tool for refractive optimization is
      warranted.

PMID- 16286797
TI  - Retinal arterial macroaneurysms: risk factors of poor visual outcome.
AB  - PURPOSE: To evaluate the long-term natural course and to identify the risk
      factors of a poor visual outcome in patients with retinal arterial macroaneurysms
      (MA). METHODS: In this observational case series, we retrospectively evaluated
      the consecutive patients with MA at our institution over a 17-year period. The
      visual outcomes of the different types of MA (presented as predominantly
      hemorrhagic or exudative) were compared. RESULTS: A total of 31 patients with 46
      confirmed MA were identified. The ocular manifestations of MA included retinal
      hemorrhage (96.7%), retinal exudate (61.3%), macular involvement (77.4%) and
      vitreous hemorrhage (12.9%). Among the 10 cases of hemorrhagic-type MA, visual
      acuity improved by 2 or more lines in 9 (90%) and decreased in 1 patient (10%).
      In the 15 cases of exudative-type MA, 4 improved (26.7%), 8 remained stationary
      (53.3%) and 3 had decreased visual acuity (20.0%). The average vision change in
      the minimum angle of resolution improved by 0.59 log units in hemorrhagic MA and
      decreased by 0.07 log units in exudative MA (p < 0.01). With respect to change of
      vision, the eyes with hemorrhagic-type MA showed greater improvement than those
      with the exudative type, but the final visual outcome was not different in the 2
      groups. Foveal exudate was a statistically significant risk factor for final
      vision equal to or worse than 6/30 (odds ratio = 6.93, p < 0.05). CONCLUSIONS:
      Different types of MA may have different clinical presentations. In the majority
      of MA, there is gradual and spontaneous involution. However, poor visual outcome
      may occur secondary to foveal exudates and subfoveal hemorrhage.

PMID- 16286798
TI  - Comparison of diagnostic ability between a fast strategy, tendency-oriented
      perimetry, and the standard bracketing strategy.
AB  - PURPOSE: To compare the diagnostic abilities of the standard bracketing strategy
      (BR) and a fast strategy, the tendency-oriented perimetry (TOP). METHODS: Seventy
      seven controls and 91 eyes from patients with glaucoma were analyzed with the
      strategies TOP and BR. Sensitivity (Se), specificity (Sp), the area under the
      receiver operating characteristic (ROC) curve (AC) and the optimum cutoff value
      (CO) were calculated for the visual field indices mean defect (MD), the square
      root of the loss variance (sLV) and the number of pathological points (NPP).
      RESULTS: In the glaucoma group, the mean MD value using TOP and BR was 7.5 and
      8.3 dB, respectively. The mean sLV value using TOP and BR was 5.0 and 5.3 dB,
      respectively. Indices provided by TOP had higher ROC values than the ones
      provided by BR. Using TOP, the index with the best diagnostic ability was sLV (Sp
      = 94.8, Se = 90.1, AC = 0.966, CO = 2.5 dB), followed by NPP and MD. Using BR,
      the best results were obtained for MD (Sp = 92.2, Se = 81.3, AC = 0.900, CO = 2.5
      dB) followed by sLV and NPP. CONCLUSIONS: A fast strategy, TOP, had superior
      diagnostic ability than the standard BR. Although TOP provided lower LV values
      than BR, the diagnostic ability of this index was higher than that of the
      conventional strategy.

PMID- 16286799
TI  - Detection of early diabetic change with optical coherence tomography in type 2
      diabetes mellitus patients without retinopathy.
AB  - PURPOSE: To detect early diabetic damage in type 2 diabetes mellitus patients
      with no diabetic retinopathy (NDR) using optical coherence tomography (OCT) and
      to evaluate OCT as a clinical test. METHODS: Thirty-two patients with NDR (n =
      32) were enrolled. We examined retinal and retinal nerve fiber layer (RNFL)
      thickness using OCT. Two healthy normal populations were also enrolled for the
      retinal thickness (n = 48) and RNFL thickness (n = 34). Both OCT measurements
      were obtained in four areas (temporal, superior, nasal and inferior). The
      receiver operator characteristic (ROC) curve was generated to evaluate the
      predictor variables. RESULTS: Comparing the normal and NDR eyes, retinal
      thickness significantly increased (p = 0.03) and RNFL thickness significantly
      decreased (p = 0.02) in the superior areas. The area under the ROC curve was 0.65
      for the superior retinal thickness and 0.63 for the superior RNFL thickness.
      CONCLUSIONS: Both OCT measurements can detect early retinal damage in NDR
      patients.

PMID- 16286800
TI  - The role of a second isolated retinal artery in branch retinal vein obstruction.
AB  - PURPOSE: To evaluate the prevalence of a second isolated retinal artery in eyes
      with and without branch retinal vein obstruction (BRVO). METHODS: A retrospective
      study of the color photographs and fluorescein angiograms of 100 patients with
      unilateral BRVO (64 superotemporal and 34 inferotemporal) and a control group of
      33 patients (66 eyes) with different ailments was made. The prevalence of a
      second isolated retinal artery, which coursed closer to the macular region, in
      BRVO eyes, fellow eyes and eyes of the control group was evaluated. The types and
      sites of arteriovenous crossings were also recorded for comparison. RESULTS: The
      eyes with BRVO, which involved the superotemporal quadrant, had significantly
      larger numbers of arteriovenous crossings than did fellow eyes (p = 0.02) and
      control eyes (p = 0.001). In the superotemporal quadrant, a significantly higher
      percentage (35 of 66, 53%) of the control eyes had a second isolated retinal
      artery than did BRVO eyes (16 of 64 cases, 25%, p = 0.001). CONCLUSIONS: The
      second isolated retinal artery, which has not been previously mentioned in the
      literature, may lower the chance of arteriovenous crossings and play a protective
      role in BRVO.

PMID- 16286801
TI  - A retrospective analysis of five intra-ocular lenses and the predictive value of
      six different intra-ocular lens power calculation formulas.
AB  - PURPOSE: To evaluate the refractive and visual outcome after implantation of five
      different lenses and to evaluate the accuracy of six different intra-ocular lens
      (IOL) power formulas. SETTING: Department of Ophthalmology, University Medical
      Centre Rotterdam, The Netherlands. METHODS: In total, 288 eyes had cataract
      surgery with implantation of a polymethylmethacrylate lens (Centra55B) or a
      foldable silicone lens (AMO SI40, Staar AA, Silens 5, Pliolens). The pre- and
      postoperative refraction and visual outcome were analysed for all lenses under
      study. Six different IOL power formulas have been used to compare the accuracy of
      the predictive refractive outcome. RESULTS: The Staar Plate Haptic lens was found
      to have the best uncorrected visual acuity (UCVA) compared to the Centra55B, AMO
      SI40 and the Pliolens. Based on the A constant given by the company, the Pliolens
      revealed a significant overcorrection and the Staar Plate Haptic lens an
      undercorrection. The achieved postoperative refraction minus the intended
      postoperative refraction caused significant myopia with the Pliolens and
      hyperopia with the Staar Plate Haptic lens. The SRK-T and the Holladay formulas
      give the best predictive lens calculations in relation to the axial length.
      CONCLUSION: The A constant of all lenses has to be adjusted for our institute.
      Especially the AMO SI40, the Staar AA lens and the Silens 5 showed a remarkable
      difference compared to the A constant given by the company. All foldable lenses
      were comparable in their visual outcome. The significantly better UCVA of the
      Staar Plate Haptic lens can be explained by the emmetropic outcome of the
      postoperative refraction.

PMID- 16286802
TI  - Intravitreal cortisone injection for refractory diffuse diabetic macular edema.
AB  - PURPOSE: The purpose of this study was to evaluate the safety and efficacy of
      intravitreal triamcinolone acetonide injection in patients with diffuse diabetic
      macular edema. We also compared the effect of intravitreal triamcinolone with
      macular grid laser photocoagulation in macular edema. PATIENTS AND METHODS:
      Thirty patients with diabetic diffuse macular edema unresponsive to grid laser
      photocoagulation for at least 4 months received 0.1 ml (4 mg/ml) intravitreal
      triamcinolone acetonide (Kenakort-A) injection as treatment. This study group was
      compared with a control group of 30 patients (30 eyes) who had undergone grid
      laser macular coagulation. Mean follow-up time was 17 months (range 14-24 months)
      in the study group and 19 months (range 16-24 months) in the control group.
      RESULTS: In the study group, mean improvement in visual acuity measured 3.8, 3.4,
      0.9 and 0.2 Snellen lines at the follow-up intervals of 1, 3, 6 and 12 months,
      respectively. Improvement in visual acuity was statistically significant only at
      1 month (p = 0.002) and 3 months (p = 0.003) after injection. Visual acuity was
      significantly (p < 0.05) better in the study group than the control group at 1
      and 3 months. Overall, 6 of 30 eyes (20%) required a second injection and 3 eyes
      (10%) a third due to regression in visual acuity. Towards the end of the follow
      up period, the visual acuity decreased to almost baseline levels. Elevation of
      intraocular pressure was found in 4 patients and controlled with topical
      antiglaucomatosis treatment. Sterile endophthalmitis was detected in only one
      eye. No eye exhibited cataract progression during the follow-up period.
      CONCLUSION: Intravitreal injection of triamcinolone may be beneficial for
      temporarily increasing visual acuity in patients with diabetic diffuse macular
      edema who are unresponsive even to grid laser photocoagulation. But the
      regression of visual acuity looks inevitable in the long term after injection.
      Therefore, repeated injections with/without increasing doses might be required
      for the stabilization of visual acuity.

PMID- 16286803
TI  - A case of Coats' disease in a low-birth-weight infant.
AB  - PURPOSE: To report a rare case of Coats' disease in a 3-month-old male infant.
      METHOD: Interventional case report. We examined a male infant, born at 33 weeks
      of gestation, who did not receive ventilation with oxygen after birth. RESULT: In
      this patient, the left fundus showed telangiectasia and tortuosity at 3 months of
      age. His right eye showed no abnormality in the fundus. A month later, in
      addition to the presence of abnormal vessels, microaneurysms and exudation also
      appeared. The patient was diagnosed to have Coats' disease and both the abnormal
      vessels and microaneurysms in the temporal fundus were treated by laser
      photocoagulation. Six months later, the left fundus showed a resolution of the
      abnormal vessels and exudation. CONCLUSION: Most instances of Coats' disease
      occurring in an infant tend to already be severely advanced when diagnosed. Early
      and appropriate treatment of patients with Coats' disease makes it possible to
      stabilize and thus improve the outcome.

PMID- 16286804
TI  - Multifocal electroretinography changes in the macula at high altitude: a report
      of three cases.
AB  - BACKGROUND: To evaluate the short- and long-term effects of high-altitude
      hypobaric hypoxia on macula morphology and function during ascents,
      acclimatizations, and descents between 500 m and 5,650 m, macula function was
      evaluated in three healthy climbers of a trekking expedition. METHODS: Macula
      physiology was tested with multifocal electroretinography (MF ERG), near and
      farvisual acuity, and Amsler grid tests. Macula morphology was tested with
      optical coherence tomography (OCT) and with stereoscopic fundoscopy obtained 1
      week before ascent, as well as 1 week and 2 weeks after high-altitude exposure.
      The following physiological parameters indicative of acclimatization were
      compared daily during the expedition at altitudes between 500 m and 5,050 m:
      hemoglobin, oxygen saturation, resting heart rate, retinal findings, and the Lake
      Louise score of acclimatization. RESULTS: The central macula MF ERG responses
      were significantly reduced 1 week after high-altitude exposure, and had recovered
      by the follow-up examination performed during the following week. Near visual
      acuity and Amsler grid tests remained unaffected at both follow-up examinations.
      No significant changes were found in the follow-up OCT and daily fundoscopy
      examinations in all three well-acclimatized climbers. CONCLUSIONS: High-altitude
      hypobaric hypoxia affects the function of the highly sensitive macula region.
      This suggests that the exposure of persons with macula diseases such as age
      related macula degeneration, tapetoretinal degeneration, or diabetic retinopathy
      to high altitudes may influence the disease progression. For this reason, this
      population should avoid prolonged and unnecessary high-altitude exposure without
      proper acclimatization.

PMID- 16286806
TI  - Fear from visual experiences during cataract surgery.

PMID- 16286805
TI  - Refractory severe ocular hypertension after intravitreal triamcinolone acetonide
      injection.
AB  - PURPOSE: To report a serious complication following intravitreal triamcinolone
      acetonide injection. METHODS: Observational case report. RESULTS: In 2 patients,
      secondary intractable severe ocular hypertension occurred 2 months after a single
      4-mg intravitreal injection of triamcinolone acetonide for macular edema. Both
      patients required trabeculectomy intervention to control intraocular pressure
      (IOP). CONCLUSION: We highlight the occurrence of intractable high IOP elevation
      as a serious complication 2 months after intravitreal triamcinolone acetonide.
      Cautious monitoring of IOP for several months after this therapy is recommended.
      The risks of this potentially devastating complication need to be weighed against
      the benefits of intravitreal triamcinolone in the individual patient.

PMID- 16286808
TI  - Antioxidant potential of thymol determined by chemiluminescence inhibition in
      human neutrophils and cell-free systems.
AB  - Thyme essential oil and thymol have antimicrobial, antifungal and antioxidant
      activities. Their antioxidant activity has been studied almost exclusively by
      means of chemical testing in order to be able to use it for food preservation
      purposes. The aim of this luminol amplified chemiluminescence (LACL) study was to
      investigate whether thymol can interfere with the production of reactive oxygen
      species, nitric oxide and the nitric oxide-derived peroxynitrite released by
      human neutrophils after activation by fMLP and PMA with and without the addition
      of the L-arginine (L-Arg) nitric oxide donor to the medium. The lowest thymol
      concentration that was still active in reducing LACL was 2.73 microg/ml, and
      there was a progressive linear inhibition of LACL from this concentration to
      21.87 microg/ml, the highest thymol concentration investigated. This was also
      observed in the case of both fMLP and PMA stimulation with or without L-Arg. In
      cell-free systems using H(2)O(2)/HOCl(-) and SIN-1 as radical producers, a
      significant scavenging activity of thymol was present already at 0.08 and 0.68
      microg/ml respectively, and these are very low concentrations. These findings can
      be related to the phenolic structure of thymol, because phenolic compounds have
      redox properties and play an important role in adsorbing and neutralizing free
      radicals and peroxynitrite, and in decomposing peroxides. Our findings in human
      neutrophils are pharmacologically relevant as they imply that thymol is a
      potential antioxidant and anti-inflammatory agent in human cells.

PMID- 16286809
TI  - Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats.
AB  - Diabetic nephropathy is a serious microvascular complication and one of the main
      causes of end-stage renal disease. Various studies have revealed that increased
      oxidative stress is a major pathophysiological mechanism which is involved in the
      etiology of diabetic nephropathy. Resveratrol, a polyphenolic phytoalexin present
      in red wine, is known to possess potent antioxidant properties and thus we aimed
      to examine its effect on renal function and oxidative stress in streptozotocin
      (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal
      injection of STZ (65 mg/kg) in rats. After 4 weeks of STZ injection, rats were
      divided into four groups: the control rats, diabetic rats and diabetic rats
      treated with resveratrol (5 and 10 mg/kg, orally) respectively from week 4 up
      till week 6. At the termination of the experiments, urine albumin excretion,
      urine output, serum creatinine, blood urea nitrogen, creatinine and urea
      clearance were measured. The levels of the renal oxidative stress markers
      malonaldehyde and glutathione and the antioxidant enzymes superoxide dismutase
      and catalase were measured in kidney homogenate. STZ-injected rats showed
      significant increases in blood glucose, polyuria, proteinuria and a decrease in
      body weight compared with age-matched control rats. After 6 weeks, diabetic rats
      exhibited renal dysfunction, as evidenced by reduced creatinine and urea
      clearance, and proteinuria along with a marked increase in oxidative stress, as
      determined by lipid peroxidation and activities of key antioxidant enzymes.
      Treatment with resveratrol significantly attenuated renal dysfunction and
      oxidative stress in diabetic rats. The present study reinforces the important
      role of oxidative stress in diabetic kidney and points towards the possible
      antioxidative mechanism being responsible for the renoprotective action of
      resveratrol.

PMID- 16286810
TI  - Ultra-low dose naltrexone enhances cannabinoid-induced antinociception.
AB  - Both opioids and cannabinoids have inhibitory effects at micromolar doses, which
      are mediated by activated receptors coupling to Gi/o-proteins. Surprisingly, the
      analgesic effects of opioids are enhanced by ultra-low doses (nanomolar to
      picomolar) of the opioid antagonist, naltrexone. As opioid and cannabinoid
      systems interact, this study investigated whether ultra-low dose naltrexone also
      influences cannabinoid-induced antinociception. Separate groups of Long-Evans
      rats were tested for antinociception following an injection of vehicle, a sub
      maximal dose of the cannabinoid agonist WIN 55 212-2, naltrexone (an ultra-low or
      a high dose) or a combination of WIN 55 212-2 and naltrexone doses. Tail-flick
      latencies were recorded for 3 h, at 10-min intervals for the first hour, and at
      15-min intervals thereafter. Ultra-low dose naltrexone elevated WIN 55 212-2
      induced tail flick thresholds without extending its duration of action. This
      enhancement was replicated in animals receiving intraperitoneal or intravenous
      injections. A high dose of naltrexone had no effect on WIN 55 212-2-induced tail
      flick latencies, but a high dose of the cannabinoid 1 receptor antagonist SR
      141716 blocked the elevated tail-flick thresholds produced by WIN 55 212-2+ultra
      low dose naltrexone. These data suggest a mechanism of cannabinoid-opioid
      interaction whereby activated opioid receptors that couple to Gs-proteins may
      attenuate cannabinoid-induced antinociception and/or motor functioning.

PMID- 16286812
TI  - Cross-tolerance between antinociception induced by swim-stress and morphine in
      formalin test.
AB  - The present study investigated cross-tolerance between antinociception induced by
      water swim-stress and morphine in the formalin test. Intraperitoneal
      administration of morphine (3, 6 and 9 mg/kg) induced dose-dependent
      antinociception in both phases of the formalin test. Mice treated with a lower
      dose of morphine (25 mg/kg), once daily for 3 days, showed tolerance to
      antinociception induced by a lower test dose of morphine (3 mg/kg). Similar
      repeated treatments with a higher dose of morphine (50 mg/kg) produced tolerance
      to antinociception induced by different test doses of morphine (3, 6 and 9
      mg/kg). Exposure to water swim-stress, once daily for 2 or 3 days in order to
      induce tolerance, also decreased morphine-induced antinociception. Swim-stress
      exposure for 2 or 3 days also tends to potentiate tolerance induced by a lower
      dose of morphine. Acute swim-stress of different durations (0.5, 1 and 3 min)
      induced antinociception in both phases of the formalin test, which was not
      reduced by naloxone, but showed even more antinociception in the second phase.
      The response to swim stress was decreased in mice treated with higher doses of
      morphine, but not those animals that received swimming stress (3 min) once daily
      for 2-3 days, in order to induce habituation to swim-stress-induced
      antinociception. The results may indicate a possible cross-tolerance between
      antinociception induced by morphine and by swim stress.

PMID- 16286811
TI  - Action of ondansetron and CP-99,994 on cisplatin-induced emesis and locomotor
      activity in Suncus murinus (house musk shrew).
AB  - Species possessing the emetic reflex are useful for anti-emetic screening.
      Assessing the potential of novel drugs to simultaneously reduce nausea and emesis
      in animals is problematic, however. In the present studies, therefore, the
      behavioural repertoire of Suncus murinus in response to the emetic
      chemotherapeutic drug cisplatin was studied in an attempt to characterize
      behaviours (including spontaneous locomotor activity) that may be relevant to
      nausea status. Cisplatin at 30 mg/kg, intraperitoneal, induced a robust emetic
      response but did not induce novel behaviour and failed to affect spontaneous
      locomotor activity. Ondansetron at 3 mg/kg, subcutaneous, and CP-99,994 at 10
      mg/kg, subcutaneous, reduced emesis by 98% and 40.7%, respectively. Both
      ondansetron and CP-99,994, however, were inactive in modifying spontaneous
      locomotor activity in either cisplatin-treated or normal animals. Results are
      discussed in relation to other animal models of nausea and emesis.

PMID- 16286813
TI  - Subchronic intermittent caffeine administration to unilaterally 6-hydroxydopamine
      lesioned rats sensitizes turning behaviour in response to dopamine D(1) but not
      D(2) receptor agonists.
AB  - The effects of caffeine, an antagonist of adenosine A(1) and A(2A) receptors, are
      significantly influenced by modifications in dopamine transmission.
      Administration of caffeine to unilaterally 6-hydroxydopamine-lesioned rats
      induces ipsilateral turning behaviour in rats never exposed to a dopamine
      receptor agonist, whereas contralateral turning is elicited if rats are
      repeatedly primed with a dopamine receptor agonist. In this study, rats
      unilaterally lesioned with 6-hydroxydopamine and subchronically treated with an
      intermittent administration of caffeine (15 mg/kg) or vehicle, were administered,
      3 days after discontinuations of the treatment, with the dopamine D(1) receptor
      agonist 1-phenyl 1,2,3,4,5-tetrahydro(1H)-3-benzazepine-7,8-diolhydrochloride
      (SKF 38393), the D(2)/D(3) receptor agonist quinpirole, the D(2) receptor agonist
      R(-)-propylnorapomorphine or the dopamine precursor L-3,4-dihydroxyphenyl
      alanine. Administration of SKF 38393 (1.5 mg/kg) or L-3,4-dihydroxyphenyl-alanine
      (6 mg/kg), but not quinpirole (0.15 mg/kg) or R(-)-propylnorapomorphine (0.01
      mg/kg), induced a significantly higher contralateral turning behaviour in rats
      subchronically treated with caffeine than in vehicle-pretreated rats. The results
      show that repeated intermittent caffeine exposure enhances the motor stimulant
      effects elicited by dopamine agonists by a preferential sensitization of dopamine
      D(1) receptors.

PMID- 16286814
TI  - Kappa-opioid receptor-mediated effects of the plant-derived hallucinogen,
      salvinorin A, on inverted screen performance in the mouse.
AB  - Salvinorin A is a pharmacologically active diterpene that occurs naturally in the
      Mexican mint Ska Maria Pastora (Salvia divinorum) and represents the first
      naturally occurring kappa-opioid receptor agonist. The chemical structure of
      salvinorin A is novel among the opioids, and thus defines a new structural class
      of kappa-opioid-receptor selective drugs. Few studies have examined the effects
      of salvinorin A in vivo, and fewer still have attempted to assess the agonist
      actions of this compound at mu-opioid, delta-opioid, and kappa-opioid receptors
      using selective antagonists. In the mouse, salvinorin A disrupted climbing
      behavior on an inverted screen task, indicating a rapid, but short-lived
      induction of sedation/motor incoordination. Similar effects were observed with
      the mu-agonist remifentanil and the synthetic kappa-agonist U69,593. When
      behaviorally equivalent doses of all three opioids were challenged with
      antagonists at doses selective for mu-opioid, delta-opioid, or kappa-opioid
      receptors, results suggested that the motoric effects of remifentanil were
      mediated by mu-receptors, whereas those of salvinorin A and U69,593 were mediated
      via kappa-receptors. Despite similar potencies and degrees of effectiveness,
      salvinorin A and U69,593 differed with regard to their susceptibility to
      antagonism by the kappa-antagonist nor-binaltorphamine. This later finding,
      coupled with the novel chemical structure of the compound, is consistent with
      recent findings that the diterpene salvinorin A may bind to the kappa-receptor in
      a manner that is qualitatively different from that of more traditional kappa
      agonists such as the benzeneacetamide U69,593. Such pharmacological differences
      among these kappa-opioids raise the possibility that the development of other
      diterpene-based opioids may yield important therapeutic compounds.

PMID- 16286815
TI  - An ionotropic but not a metabotropic glutamate agonist potentiates the
      pharmacological effects of olanzapine in the rat.
AB  - This study aimed to evaluate the possible potentiating action of ionotropic or
      metabotropic (metabotropic glutamate receptor type 5) glutamate agonists on
      pharmacological effects induced in rats by the atypical antipsychotic olanzapine.
      The administration of doses of olanzapine, which did not affect spontaneous
      motility, inhibited behaviors induced by the selective stimulation of 5HT(2A) and
      D(2) receptors. In particular, 0.03 or 0.06 mg/kg of olanzapine was sufficient to
      reduce, respectively, head shakes induced by the 5HT(2A) agonist 1-2,5-dimethoxy
      4-iodophenyl-2-aminopropane (1 mg/kg) or hypermotility elicited by the D(2)
      stimulant quinpirole (0.15 mg/kg). Behavioral responses to a D(1)/D(2) agonist
      (apomorphine-induced stereotypies) were inhibited by doses of olanzapine that
      also influenced spontaneous behavior. The concomitant administration of D
      cycloserine, an agonist at the glycine site on the N-methyl-D-aspartate receptor
      complex, given at a dose (3 mg/kg) that did not affect behavior, increased the
      inhibitory effect of olanzapine on the responses produced by 5HT2A, D(2) and
      D(1)/D(2) receptor stimulation. The concomitant administration of 2-chloro-5
      hydroxyphenylglycine, an agonist of metabotropic glutamate receptor type 5,
      increased the inhibitory effect of olanzapine on the behaviors induced by the
      stimulation of D(2), but not 5HT2A or D(1)/D(2) receptors. As the effect on the
      serotonergic system seems important for the unusual pharmacological profile of
      atypical antipsychotics, the present results suggest that N-methyl-D-aspartate,
      but not metabotropic glutamate receptor type 5 agonists could be seen as
      promising therapeutic agents for increasing the pharmacological effects of
      olanzapine.

PMID- 16286816
TI  - The effects of histaminergic agents in the central amygdala of rats in the
      elevated plus-maze test of anxiety.
AB  - Reports indicate that histamine and histaminergic agents can change anxiety
      related behaviours in both animals and humans. The amygdala is an important brain
      site in the modulation of fear or anxiety. In the present study, we investigated
      the effects of intracentral amygdala microinjection of histaminergic agents on
      anxiety-related behaviours in rats, using the elevated plus-maze test of anxiety.
      Intracentral amygdala administration of histamine (0.01-0.5 microg/0.5 microl
      bilateral) decreased %open armtime and % open arm entries, but not locomotor
      activity, showing an anxiogenic response. Intracentral amygdala microinjection of
      pyrilamine (H1 receptor antagonist) and ranitidine (H2 receptor antagonist) (both
      at 1-20 microg/0.5 microl bilateral) did not change anxiety-related parameters in
      our experiments. In another series of experiments, histamine (0.5 microg/0.5
      microl bilateral) was coadministrated with pyrilamine and ranitidine (both at 1
      20 mg/0.5 microl bilateral). The results showed that pyrilamine but not
      ranitidine could significantly reverse the anxiogenic effect of histamine at
      doses of 10 and 20 microg/0.5 microl bilateral. The results suggest that
      histamine may modulate anxiety via H1 but not H2 receptors in the rat central
      amygdala.

PMID- 16286817
TI  - Extract of Ginkgo biloba leaves reverses yohimbine-induced spatial working memory
      deficit in rats.
AB  - Extract of Ginkgo biloba is used to alleviate age-related decline in cognitive
      function, which may be associated with the loss of catecholamines in the
      prefrontal cortex. The purpose of this study was to verify whether alpha-2
      adrenergic activity is involved in the facilitative effects of extract of Ginkgo
      biloba on prefrontal cognitive function. Male Wistar rats were trained to reach
      criterion in the delayed alternation task (0, 25, and 50-s delay intervals). A
      pilot study found that 3 or 4 mg/kg of yohimbine (intraperitoneal) reduced the
      choice accuracy of the delayed alternation task in a dose and delay-dependent
      manner, without influencing motor ability or perseverative behaviour. Acute oral
      pre-treatment with doses of 50, 100, or 200 mg/kg (but not 25 mg/kg) of extract
      of Ginkgo biloba prevented the reduction in choice accuracy induced by 4 mg/kg
      yohimbine. These data suggest that the prefrontal cognition-enhancing effects of
      extract of Ginkgo biloba are related to its actions on alpha-2-adrenoceptors.

PMID- 16286818
TI  - Reduction of Submissive Behavior Model for antidepressant drug activity testing:
      study using a video-tracking system.
AB  - Submissive animals can be defined in a food competition test as spending
      significantly less time on the feeder than their dominant partners. Using
      observer-based scoring in the Reduction of Submissive Behavior Model, submissive
      behavior in rats and mice has been previously shown to be sensitive and selective
      to antidepressant treatment. In this paper, we report the use of automated
      scoring by a multiple-subject video-tracking system to record similar effects of
      antidepressants on rat submissive behavior. Automated scoring enabled the
      observation of four pairs of rats during each 5-min experimental session (one
      set) and immediate switching to the observation of the next four pairs of
      animals. Studies were conducted to confirm our previous results with imipramine
      and fluoxetine that were obtained with manual scoring, and to extend those
      results to studies with other drugs, including the antidepressant maprotiline and
      the delta-opioid antagonist naltrindole, which is not known to have
      antidepressant activity. As in previous studies, treatment of the submissive
      animal for 5 weeks with imipramine (20 mg/kg) or fluoxetine (10 mg/kg)
      significantly reduced submissive behavior, with a delayed onset of antidepressant
      effect that was dependent on drug dose. Maprotiline (10 and 20 mg/kg), like
      imipramine or fluoxetine and in contrast to naltrindole, strongly reduced rat
      submissive behavior, further demonstrating the selectivity of this test for
      antidepressant activity.

PMID- 16286819
TI  - Effects of the long-lasting kappa opioid 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)
      1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl) ethyl] acetamide in a drug
      discrimination and warm water tail-withdrawal procedure.
AB  - Although studies suggest that 2-(3,4-dichlorophenyl-N-methyl-N-[(1S)-1-(3
      isothiocyanatophenyl)-2-(1-pyrrolidinyl) ethyl] acetamide (DIPPA) has transient
      kappa-opioid-mediated agonist effects followed by long-lasting kappa-antagonist
      effects, its behavioral and pharmacological actions have not been systematically
      examined and there is evidence suggesting that some of its effects are species
      dependent. The purpose of this investigation was to examine the actions of DIPPA
      in different behavioral procedures and in three species. In a pigeon drug
      discrimination procedure, DIPPA and the kappa-opioids U50,488 and ICI-199441
      substituted fully for the stimulus effects produced by spiradoline. For DIPPA,
      this effect was observed between 0.25 and 4 h after administration. In a warm
      water tail-withdrawal procedure, DIPPA failed to produce antinociception in rats
      or mice even when relatively high doses were tested using pretreatment intervals
      ranging from 0.25 to 24 h. In this procedure, DIPPA antagonized the effects of
      spiradoline and U50,488 in mice. In rats, DIPPA antagonized the effects of
      U50,488 but not those of spiradoline. Taken together, these results suggest that
      DIPPA may function as a low-efficacy kappa-opioid and have a long duration of
      action, and there may be some species differences in its behavioral profile. This
      profile of action, however, differs from other low-efficacy kappa-opioids.

PMID- 16286824
TI  - Difficult-to-manage vaginitis.

PMID- 16286825
TI  - Vulvodynia: strategies for treatment.

PMID- 16286827
TI  - An overview of lichen sclerosus.

PMID- 16286826
TI  - Overview of vulvar pruritus through the life cycle.

PMID- 16286828
TI  - Vulvar lichen planus.

PMID- 16286829
TI  - An overview of vulvar ulceration.

PMID- 16286830
TI  - Genital herpes simplex virus infection.

PMID- 16286831
TI  - Squamous vulvar intraepithelial neoplasia.

PMID- 16286832
TI  - Superficially invasive carcinoma of the vulva: diagnosis and treatment.

PMID- 16286833
TI  - Surgery for vulvar cancer.

PMID- 16286836
TI  - Fetal therapy for single gene disorders.

PMID- 16286834
TI  - Recurrent vulvar cancer.

PMID- 16286837
TI  - Alloimmune thrombocytopenia.

PMID- 16286838
TI  - Percutaneous fetal endoscopic tracheal occlusion (FETO) for severe left-sided
      congenital diaphragmatic hernia.

PMID- 16286839
TI  - Fetal obstructive uropathy.

PMID- 16286840
TI  - Intrauterine repair of spina bifida.

PMID- 16286841
TI  - Fetal cardiac interventions.

PMID- 16286842
TI  - Gastroschisis.

PMID- 16286843
TI  - Twin-to-twin transfusion syndrome: management options and outcomes.

PMID- 16286846
TI  - Dietetic practitioners. Part II: how much do we earn?

PMID- 16286847
TI  - The new dietary guidelines: dietitians play a key role in helping to launch
      MyPyramid.

PMID- 16286849
TI  - Exercise and lymphocyte activation following chemotherapy for breast cancer.
AB  - PURPOSE: To determine whether exercise training would increase lymphocyte
      activation in patients with breast cancer following chemotherapy. Activation was
      determined by the presence of CD4(+)CD69(+) T-helper lymphocytes, mitogen-induced
      proliferation, and levels of cytokines produced by mitogen-stimulated lymphocytes
      and in the patients' plasma. METHODS: Patients with breast cancer (N = 28) who
      participated in a 6-month exercise program were compared with patients (N = 21)
      who did not exercise. Following chemotherapy, and 3 and 6 months later, patients
      underwent fitness evaluations and had blood drawn. The exercise program consisted
      of resistance training and aerobic activity at 60-75% functional capacity three
      times a week with a personal trainer. Immunochemistry and flow cytometry were
      used to measure the number of CD4(+)CD69(+) blood lymphocytes. Whole blood was
      stimulated with concanavalin A (ConA), phytohemagglutin (PHA), or pokeweed
      mitogen (PWM) to determine proliferation potential. Enzyme-linked immunosorbent
      assays (ELISA) were used to determine the concentration of interferon-gamma (IFN
      gamma) and interleukin-6 (IL-6) in the culture medium of mitogen-stimulated
      lymphocytes as well as the plasma concentrations of IL-6, soluble IL-6 receptor,
      soluble gp130, and IFN-gamma. Analysis of groups across time was done using the
      Wilcoxon signed rank test, and comparisons of groups were done using the Mann
      Whitney U test. RESULTS: The exercising patients showed increases in maximal
      oxygen uptake and upper body strength. This group also showed a greater
      percentage of CD4(+)CD69(+) cells and a greater level of tritiated thymidine
      incorporation (DNA synthesis) when stimulated with ConA, PHA, and PWM at the end
      of the intervention. Plasma and mitogen-stimulated IL-6 and IFN-gamma production
      were similar in both groups. CONCLUSION: Exercise may improve immune function by
      increasing lymphocyte activation in patients with breast cancer following
      treatment.

PMID- 16286850
TI  - Perceived exertion during prepregnancy physical activity and preeclampsia risk.
AB  - PURPOSE: Studies have shown that absolute intensity of physical activity is
      associated with reduced risk of preeclampsia. This analysis was performed to
      examine whether relative intensity may also be related to preeclampsia risk.
      METHODS: Using data from a case-control study conducted from 1998 to 2002, the
      authors assessed the relation between perceived exertion (i.e., relative
      intensity) during usual recreational physical activity in the year before
      pregnancy and risk of preeclampsia. In a structured interview conducted during
      postpartum hospitalization, 244 preeclampsia cases and 470 normotensive controls
      provided details on their recreational physical activities in the year before
      pregnancy. RESULTS: Participants who reported feeling very strenuous to maximal
      exertion during usual prepregnancy physical activity were 78% less likely to have
      developed preeclampsia than those who reported negligible or minimal exertion
      (adjusted odds ratio 0.22, 95% confidence interval 0.11-0.44). A significant
      trend was noted of decreased preeclampsia risk with increased perceived exertion
      (P < 0.001). This association was independent of prepregnancy adiposity, and was
      also apparent among the subset of participants who did not meet physical activity
      guidelines in the year before pregnancy. CONCLUSIONS: In this study, relative
      intensity of recreational physical activity performed during the year before
      pregnancy was associated with a decreased risk of preeclampsia.

PMID- 16286851
TI  - Chronic alcohol intake, resistance training, and muscle androgen receptor
      content.
AB  - INTRODUCTION: Chronic alcohol intake and resistance training (RT) have opposite
      effects on muscle physiology. PURPOSE: This study examined the effect of chronic
      alcohol intake on androgen receptor (AR) content in skeletal muscle to determine
      whether this effect was influenced by RT. METHODS: A total of 48 male Sprague
      Dawley(R) rats (mass = 456 +/- 1 g; mean +/- SE) were divided into five groups:
      baseline (N = 8), sedentary + alcohol (Sed-Al) (N = 8), sedentary + normal diet
      (Sed-Nml) (N = 8), exercise + alcohol (Ex-Al) (N = 12), and exercise + normal
      diet (Ex-Nml) (N = 12). Exercise groups completed a 6 1/3-wk "squat" RT protocol;
      alcohol groups received an ethanol-rich (35% caloric content of alcohol) diet
      throughout the 6 1/3-wk period. Baseline animals were killed at the onset of the
      6 1/3-wk training period. RESULTS: Western blot analysis showed no effect of
      alcohol or RT on the AR of the extensor digitorum longus. Alcohol significantly
      reduced AR content of the rectus femoris (P < 0.05) and prevented RT-induced
      increases in AR content of the soleus. CONCLUSION: Chronic alcohol intake
      appeared to reduce the AR content of the type IIB fiber-predominant rectus
      femoris, and this reduction was not affected by RT. In the type I-predominant
      soleus, chronic alcohol intake alone had no effect but seemed to prevent RT
      induced increases in AR content.

PMID- 16286852
TI  - Association of muscular strength with incidence of metabolic syndrome in men.
AB  - PURPOSE: To examine the association between muscular strength and incidence of
      metabolic syndrome. METHODS: Participants were 3233 men (20-80 yr) initially free
      of metabolic syndrome who had two or more clinical examinations between 1980 and
      2003, including baseline muscular strength and cardiorespiratory fitness
      assessment. Metabolic syndrome was defined according to NCEP-ATP III criteria.
      Muscular strength was quantified by combining body weight-adjusted one-repetition
      maximal measures for leg and bench presses. Cardiorespiratory fitness was
      assessed by maximal treadmill test. RESULTS: A total of 480 men developed
      metabolic syndrome during a mean follow-up period of 6.7 +/- 5.2 yr. In a Cox
      regression analysis adjusted for age, the hazard ratios (95% confidence
      intervals) of metabolic syndrome associated with the incremental categories of
      muscular strength were 1.00 (referent), 0.88 (0.69-1.12), 0.77 (0.60-0.98), and
      0.54 (0.42-0.71), respectively (linear trend P < 0.0001). The inverse trend
      persisted after adjustment for smoking, alcohol intake, number of baseline
      metabolic syndrome risk factors, family history of diabetes, hypertension, and
      premature coronary disease (P = 0.004), but was attenuated (P = 0.06) when
      further adjusted for cardiorespiratory fitness. Compared with the lowest strength
      category, the highest strength category was associated with 44 and 39% lower risk
      (P < 0.05 each) of incident metabolic syndrome among normal weight body mass
      index (BMI < 25) and overweight or obese (BMI > or = 25) men, respectively. An
      inverse association of incident rates was also seen within stratum of age (20-39
      yr, P < 0.001; 40-49 yr, P < 0.01; and 50+ yr, P < 0.05). CONCLUSIONS: Muscular
      strength was inversely associated with metabolic syndrome incidence, independent
      of age and body size. Potential benefits of greater muscular strength presumably
      through resistance exercise training should be considered in primary prevention
      of metabolic syndrome.

PMID- 16286853
TI  - Heart rate variability in adolescents: relations to physical activity, fitness,
      and adiposity.
AB  - PURPOSE: We determined the degree to which variation in cardiac autonomic
      modulation was explained by race, sex, moderate-vigorous physical activity
      (MVPA), cardiovascular fitness (CVF), percent body fat (%BF), waist girth,
      subcutaneous abdominal adipose tissue (SAAT), and visceral adipose tissue (VAT).
      METHODS: Subjects were 304 adolescents; SAAT and VAT values were available for
      168 youths. Cardiac parasympathetic modulation (PM) was the root mean square of
      successive differences (RMSSD). Sympathetic-parasympathetic balance was the ratio
      of low- to high-frequency power (LFnu:HFnu). MVPA was measured with
      accelerometry, CVF with a treadmill, %BF with dual-energy x-ray absorptiometry
      (DXA), and SAAT and VAT with magnetic resonance imaging (MRI). RESULTS: Root mean
      square of successive differences was higher, and LFnu:HFnu was lower, in blacks
      than in whites. The final regression model revealed positive relations with CVF
      and MVPA, and a %BF by race by sex interaction, such that higher %BF was
      associated with lower RMSSD in black females and higher RMSSD in white females.
      Higher RMSSD was associated with lower VAT; for SAAT, the relationship was
      negative for blacks and positive for whites. For LFnu:Hfnu, a negative
      relationship was seen with MVPA and higher waist girth was associated with a
      higher ratio in blacks, but not in whites. Both higher VAT and SAAT were related
      to higher LFnu:HFnu. CONCLUSIONS: Black youths had a more favorable HRV profile
      than white youths. After controlling for age, race, and sex, more favorable HRV
      profiles were associated with more MVPA, better CVF, and less visceral and
      subcutaneous adiposity. The deleterious impact of higher adiposity was greater in
      blacks, especially females, than in whites. Enhancement of cardiac autonomic
      modulation may be a pathway through which physical activity, fitness, and
      leanness contribute to cardiovascular health early in life.

PMID- 16286854
TI  - Preferred transition speed between walking and running: effects of training
      status.
AB  - PURPOSE: This study was conducted to identify the preferred transition speed
      (PTS) between walking and running and the energetically optimal transition speed
      (ETOS), in runners and nonrunners. METHODS: A total of 19 young men were asked to
      walk on a treadmill at 5 km.h(-1). Speed was then increased by 0.2 km.h(-1) every
      minute. Subjects were instructed to start running at a particular speed they felt
      was easier. PTS for each subject was determined as the mean of the walk-run and
      the run-walk transitions. Subjects were also asked to walk and to run for 5 min
      at each of the following velocities: PTS - 1 km.h(-1), PTS - 0.5 km.h(-1), PTS,
      PTS + 0.5 km.h(-1), and PTS + 1 km.h(-1). This procedure was performed twice,
      once walking and once running, at all speeds. Physiologic measurements of oxygen
      consumption, heart rate, and rate of perceived exertion (RPE) were performed at
      each stage. EOTS was determined by plotting individual curves for each subject
      with the energy cost of locomotion as a function of velocity. RESULTS: Preferred
      transition speed was 7.23 +/- 0.25 and 7.42 +/- 0.25 km.h(-1) for nonrunners and
      runners, respectively (P > 0.05), and differed significantly (F = 16.47, alpha <
      0.001) from the EOTS, which was 8.02 +/- 0.84 km.h(-1) for nonrunners and 7.90 +/
      0.48 km.h(-1) for the runners. No significant differences were found between
      runners and nonrunners in PTS or EOTS. Running at the PTS resulted in a
      significantly lower RPE and higher energy cost than walking at the PTS in both
      groups. CONCLUSION: This study indicates that 1) the preferred PTS is slower than
      the EOTS, and 2) the PTS and EOTS are not dependent on the aerobic capacity or
      the training status.

PMID- 16286855
TI  - Arterial oxygen desaturation kinetics during apnea.
AB  - PURPOSE: To quantify the rate of arterial oxygen desaturation during apnea in
      freedivers. METHODS: Ten freedivers and ten controls undertook five maximal face
      immersion apneas in 10 degrees C water separated by 2 min of recovery.
      Electrocardiogram (ECG), blood pressure, and pulse oximetry were recorded
      continuously. Peripheral blood flow was measured by calf plethysmography every 30
      s, and venous blood samples were collected at rest and after apneas 1, 3, and 5.
      The blood was analyzed for hematocrit (Hct), lactate, and hemoglobin (Hb)
      concentration. The arterial oxygen saturation (SaO(2)) data were curve fitted
      with both a sigmoid and two-slope continuous function. RESULTS: Apnea duration
      increased with successive attempts, with freedivers achieving significantly
      longer maximal apneas (trained 246 +/- 44 s, untrained 129 +/- 39 s, P < 0.001).
      Compared with controls, freedivers displayed a significant change from baseline
      in heart rate (trained -27.2 +/- 9.5 bpm, untrained -19.7 +/- 9.3 bpm, P < 0.001)
      and mean arterial pressure (MAP) (trained 48 +/- 20.7 mm Hg, untrained 37 +/-
      10.0 mm Hg, P = 0.002), but no difference existed in peripheral blood flow, Hct,
      lactate, or Hb. The maximal slope of the SaO(2) sigmoid curve was not
      significantly different between the groups (trained -0.16 +/- 0.05%.s(-1),
      untrained -0.15 +/- 0.06%.s(-1), P = 0.26), but the DeltaSaO(2(/Deltat obtained
      from the two-slope continuous model indicated that 85% of the variance in the
      freedivers DeltaSaO(2)/Deltat could be explained by the apnea-induced
      bradycardia, preapnea vital capacity, and Hb concentration. CONCLUSIONS: The
      sigmoidal function provided no quantifiable difference in the rate of oxygen
      desaturation. The two-slope continuous method, however, indicated that freedivers
      who had larger oxygen stores and produced the largest bradycardia were able to
      slow the DeltaSaO(2)/Deltat to two to three times that of the least marked
      response.

PMID- 16286856
TI  - Delayed leukocytosis and cytokine response to high-force eccentric exercise.
AB  - PURPOSE: Delayed leukocytosis after strenuous exercise is well documented, but
      the underlying mechanisms are not clear. In this study, we investigated the
      relationship between exercise-induced muscle damage and delayed leukocytosis, by
      utilizing an extreme eccentric exercise protocol. METHODS: We obtained blood
      samples from 11 healthy men before and after 300 maximal eccentric actions with
      m. quadriceps. Maximal force-generating capacity was tested before and regularly
      during the 7 d after exercise. Blood was analyzed for leukocytes, growth hormone
      (GH), cortisol, granulocyte colony-stimulating factor (G-CSF), macrophage colony
      stimulating factor (M-CSF), interleukin (IL)-6, IL-8, monocyte chemoattractant
      protein-1 (MCP-1), macrophage inflammatory protein-1beta (MIP-1beta), creatine
      kinase (CK), C-reactive protein (CRP), complement activation products (C3bc and
      the terminal complement complex (TCC)), and chemotactic activity in plasma.
      RESULTS: The force-generating capacity was reduced by 47 +/- 5% (mean +/- SEM)
      immediately after exercise. Blood concentration of neutrophils and monocytes and
      the plasma concentration of G-CSF, IL-6, and MCP-1 peaked 6 h after exercise,
      whereas M-CSF peaked immediately after exercise. Serum concentration of GH and
      cortisol also peaked immediately after exercise, whereas the serum concentration
      of CRP and CK peaked after 2 and 4 d, respectively. At 1 h after exercise,
      chemotactic activity in plasma was increased; at the same time, concentration of
      C3bc and TCC were decreased. A positive correlation was found between the acute
      loss of force and the delayed leukocytosis (r = 0.66; P < 0.05), between peak G
      CSF and the delayed neutrophilia (r = 0.65, P < 0.05), between acute loss of
      force and changes in CK (r = 0.65, P < 0.05), between acute loss of force and
      changes in CRP (r = 0.65, P < 0.05), and between changes in GH and monocyte blood
      concentrations (r = 0.68, P < 0.05). CONCLUSION: The degree of exercise-induced
      muscle damage seems to be reflected by the magnitude of the subsequent delayed
      leukocytosis. The signal between the exercised muscle and bone marrow must be
      investigated further, but G-CSF and GH are putative mobilizing factors.

PMID- 16286857
TI  - Exercise and green tea extract stimulate fat oxidation and prevent obesity in
      mice.
AB  - INTRODUCTION/PURPOSE: The purpose of the present study was to explore the
      combined effects of dietary supplementation with green tea extract (GTE) and
      regular exercise on the development of obesity in high fat-fed C57BL/6J mice.
      METHODS: Weight and age-matched male mice were divided into 5 groups of 10 mice
      each. Groups were treated as follows: a low-fat diet and not exercised (LF), a
      high-fat diet and not exercised (HF), a high-fat diet supplemented with GTE and
      not exercised (GTE-HF), a high-fat diet and exercised regularly (EX-HF), or a
      high-fat diet supplemented with GTE and exercised regularly (GTEEX-HF). The
      exercise modality was treadmill running. RESULTS: After 15 wk, GTE alone and
      regular exercise alone caused a 47 and 24% reduction in body weight gain induced
      by the high-fat diet, respectively, and when combined, resulted in an 89%
      reduction. In visceral fat accumulation, GTE alone, exercise alone, and their
      combination caused a 58, 37, and 87% reduction, respectively. Indirect
      calorimetry showed that the GTEEX-HF group had the highest energy expenditure and
      fat utilization in the sedentary condition after 4 wk. Furthermore, the GTEEX-HF
      group utilized more fat than the EX-HF group during exercise. GTE supplementation
      increased hepatic fatty acid oxidation both in the exercised and nonexercised
      groups. In addition, when combined with regular exercise, GTE supplementation
      also stimulated skeletal muscle fatty acid oxidation. CONCLUSION: In conclusion,
      dietary GTE and regular exercise, if combined, stimulate fat catabolism not only
      in the liver but also in skeletal muscle, and attenuate high-fat diet-induced
      obesity more effectively than each alone in C57BL/6J mice.

PMID- 16286858
TI  - Nonlinear relationships between weekly walking distance and adiposity in 27,596
      women.
AB  - INTRODUCTION/PURPOSE: Data from vigorously active women (runners) suggested that
      declines in adiposity with weekly running distance were nonlinear and dependent
      on whether the women are relatively lean or fat. The purpose of the current study
      is to assess the cross-sectional relationship between the amount of moderate
      intensity physical activity (walking distance) and indicators of adiposity.
      METHODS: Cross-sectional analyses (i.e., quadratic polynomial regression,
      regression for percentiles of adiposity) of body mass index (BMI), body
      circumferences, and bra cup sizes in 27,596 women. RESULTS: The estimated percent
      reductions between walking 40-50 km.wk(-1) and <10 km.wk(-1) were greatest for
      BMI, intermediate for waist circumference and cup size, and least for hip and
      chest circumferences. The relationships of walking distance to BMI and body
      circumferences were all nonlinear (convex). In addition, the inverse relationship
      between weekly walking distance and adiposity was greatest at the highest
      percentile of BMI, body circumferences, and cup size, and least at the lowest
      percentiles. Thus, the decline in adiposity per kilometer per week increment in
      walking distance was greatest in overweight mostly sedentary women and least in
      lean active women. The decline in BMI per kilometer per week of exercise was
      greater in the walkers than previously reported for runners. However, based on
      the relationships between walking distance and percentiles of the BMI
      distribution reported here, we show that the majority of this difference is
      attributable to the leanness of the runners and greater fatness of the walker.
      CONCLUSION: These data suggest that in women the greatest benefit of walking may
      be among the most obese and that at higher weekly distances the declines in
      weight associated with walking diminish. Whether these relationships are causal
      remains to be determined.

PMID- 16286860
TI  - Musculoskeletal modeling and the prediction of in vivo muscle and joint forces.

PMID- 16286859
TI  - Physical activity and body mass index in grade 3, 7, and 11 Nova Scotia students.
AB  - PURPOSE: This study examined the average time spent in moderate or more intense
      physical activities according to weight status in randomly selected Nova Scotia
      students. METHODS: A total of 1653 students participated in this study: 575 in
      grade 3, 558 in grade 7, and 520 in grade 11. Physical activity was measured for
      seven consecutive days using MTI accelerometers. Activity counts were classified
      according to moderate (3-5.9 METs), hard (6-8.9 METs), and very hard (>9 METs)
      intensities. Height and weight were measured and body mass index (BMI)
      calculated. Centers for Disease Control and Prevention BMI criteria for age and
      sex were used to classify the students as normal weight (< or =85th percentile),
      at risk of overweight (>85th and < or =95th percentiles), and overweight (>95th
      percentile). ANOVA was used to compare the average time spent in moderate, hard,
      and very hard physical activities according to BMI status in boys and girls in
      grades 3, 7, and 11. RESULTS: Although age and sex differences existed, there
      were no significant differences in the average time spent in moderate or more
      intense physical activities in the BMI groups. CONCLUSION: Further research is
      warranted to elucidate the factors surrounding the relationship between physical
      activity and BMI in children and youths.

PMID- 16286861
TI  - Estimation of muscle forces and joint moments using a forward-inverse dynamics
      model.
AB  - PURPOSE: This paper presents a forward dynamic neuromusculoskeletal model that
      can be used to estimate and predict joint moments and muscle forces. It uses EMG
      signals as inputs to the model, and joint moments predicted are verified through
      inverse dynamics. The aim of the model is to estimate or predict muscle forces
      about a joint, which can be used to estimate the corresponding joint compressive
      forces, and/or ligament forces in healthy and impaired subjects, based on the way
      they activate their muscles. METHODS: The estimation of joint moments requires
      three steps. In the first step, muscle activation dynamics govern the
      transformation from the EMG signal to a measure of muscle activation--a time
      varying parameter between 0 and 1. In the second step, muscle contraction
      dynamics characterize how muscle activations are transformed into muscle forces.
      The final step requires a model of the musculoskeletal geometry to transform
      muscle forces to joint moments. Each of these steps involves complex, nonlinear
      relationships. RESULTS: An application is provided to demonstrate how this model
      can be used to study the forces in the healthy ankle during dynamometer trials
      and during gait. The model-predicted estimates of joint moment were found to
      match experimentally determined values closely. CONCLUSION: Neuromusculoskeletal
      models that use EMG as inputs can be employed to accurately estimate joint
      moments. The muscle forces predicted from these models can be used to better
      understand tissue loading in joints, and to provide in vivo estimates of tensile
      ligament forces and compressive cartilage loads during dynamic tasks. This tool
      has great potential for aiding in the study of injury mechanisms in sports.

PMID- 16286862
TI  - Use of an EMG-driven biomechanical model to study virtual injuries.
AB  - INTRODUCTION: How the CNS activates muscles to produce coordinated movement is a
      matter of debate and great interest. We are attempting to answer this question,
      in part, by investigating how individual muscles and groups of muscles are
      activated under different physiologic and environmental conditions. We have
      developed an EMG-driven virtual arm to assist in this endeavor. PURPOSE: To
      demonstrate how the virtual arm can be used to simulate a neuromuscular injury
      and to examine whether a virtual injury can evoke a change in muscle activation
      patterns. METHODS: The virtual arm is a three-dimensional graphical
      representation and biomechanical model of a human arm including the major flexor
      and extensor muscles crossing the elbow. The muscles are actuated based on
      experimentally recorded electromyograms. A Hill-type muscle model was used to
      predict muscle forces, which in turn were used to move the graphical display of
      the arm on the screen. Two subjects, one considered highly trained and the other
      a novice, participated in this study. Virtual movements, before and after
      simulating an injury were evaluated, and model performance was assessed by
      comparing the virtual arm-predicted moment and the actual moment generated by the
      subjects. RESULTS: The highly trained subject was proficient at controlling the
      virtual arm. For this subject, simulating a neuromuscular injury evoked a
      different pattern of activation compared to the preinjured state. CONCLUSIONS:
      The virtual arm may be a useful tool for the study of motor coordination and how
      muscle activation patterns change in response to injury. Future work involving
      more subjects and experimental conditions is planned to better assess the
      efficacy of the virtual arm as a research tool for investigating motor control
      strategies.

PMID- 16286863
TI  - A modeling framework to estimate patellofemoral joint cartilage stress in vivo.
AB  - PURPOSE: Patellofemoral (PF) pain is common among athletes and may be caused by
      increased subchondral bone stress as a result of increased stress in the
      cartilage of the femur or patella. This article presents a modeling pipeline to
      estimate in vivo cartilage stress in the PF joint. METHODS: The modeling pipeline
      uses the finite element method to calculate stresses and strains in the PF joint
      cartilage. Model inputs include an accurate geometrical representation of the
      bones and cartilage from magnetic resonance imaging (MRI), cartilage material
      properties, and an estimate of muscle forces from an EMG-driven musculoskeletal
      model. Validation is performed using PF joint contact area and patellar
      orientation measured from upright, weight-bearing MRI. Preliminary data from an
      active, pain-free subject illustrate the modeling pipeline to calculate cartilage
      stress during a static squat. RESULTS: The quasistatic finite element simulation
      reproduced the orientation of the patella to within 2.1 mm and predicted the PF
      joint contact area to within 2.3%. Octahedral shear stresses were highest in the
      central, lateral aspect of the patella cartilage with a peak of 2.5 MPa. The
      corresponding stresses in the femoral cartilage reached only 2.0 MPa. However,
      peak hydrostatic pressures were higher within the femoral cartilage (3.5 MPa)
      than the patellar cartilage (2.3 MPa). CONCLUSION: The methods presented in this
      article offer a novel approach to calculate PF joint cartilage stress in vivo.
      Future efforts will use this modeling pipeline to further our knowledge of PF
      pain and potential rehabilitation strategies.

PMID- 16286864
TI  - Simulation of biceps femoris musculotendon mechanics during the swing phase of
      sprinting.
AB  - INTRODUCTION/PURPOSE: Characterization of hamstring mechanics during sprinting is
      fundamental to understanding musculotendon injury mechanisms. The objective of
      this study was to use muscle-actuated forward dynamic simulations to investigate
      musculotendon mechanics of the biceps femoris long head during the swing phase of
      sprinting. METHODS: We used a three-dimensional linked segment model with 26 Hill
      type musculotendon actuators to simulate swing phase dynamics. Muscle excitations
      were computed that drove the linked segment model to track measured hip and knee
      motion of an individual sprinting on a treadmill. The simulations were used to
      investigate the effect of tendon compliance on the excursions and power
      development of the muscle and tendinous components of the biceps femoris.
      RESULTS: The biceps femoris musculotendon complex underwent a stretch-shortening
      cycle over the latter half of swing phase, with the shortening portion occurring
      in the final 10% of the gait cycle. Biceps femoris excitation increased markedly
      between 70 and 80% of the gait cycle and continued through the end of swing.
      Following the onset of excitation, stretch of the muscle component slowed
      considerably while the tendon lengthened and stored elastic energy. Simulating
      the sprinting movement with a more compliant tendon increased tendon elastic
      energy storage, thereby reducing peak muscle stretch and negative muscle work.
      CONCLUSIONS: Muscle-actuated forward dynamic simulation provides a powerful
      approach for investigating biomechanical factors that may contribute to the
      occurrence of hamstring musculotendon injuries.

PMID- 16286865
TI  - Neuromuscular biomechanical modeling to understand knee ligament loading.
AB  - PURPOSE: This article examines our use of EMG-driven neuromuscular biomechanical
      models to study how muscles stabilize the knee. EMG can be used to establish
      which activation patterns are used by people for knee stabilization. However, it
      does not reveal the effectiveness of these patterns. The EMG-driven models
      provide quantitative comparisons of the effectiveness of the different knee
      stabilizing activation patterns. METHODS: Subjects performed static tasks and
      common sporting maneuvers that challenged knee joint stability. EMG, joint
      posture and motion, and external forces and moments were measured during these
      tasks. These data were used to calibrate the EMG-driven neuromuscular
      biomechanical model. We then used the model to predict the role of muscles in
      supporting varus and valgus moments at the knee. RESULTS: We found specific
      muscle activation patterns to support varus and valgus moments. The most potent
      activation pattern to stabilize the knee is when the hamstrings or quadriceps are
      required to generate flexion or extension moments, respectively. The next most
      effective knee-stabilizing pattern is cocontraction of the hamstring and
      quadriceps. The small biarticular muscles at the knee provided the least support
      of varus and valgus moments. In the sporting tasks, sidestepping was found to
      place the anterior cruciate ligament at high risk of injury. We found that the
      muscles are the main defense against knee ligament injuries in these tasks.
      CONCLUSION: Traditional biomechanical and neurophysiological methods have shown
      that there are specific activation patterns used to stabilize the knee. By also
      using the EMG-driven neuromuscular biomechanical model, we have shown how
      effective muscles are in stabilizing the knee. This modeling method provides a
      new tool to understand knee joint stabilization.

PMID- 16286866
TI  - Muscle, ligament, and joint-contact forces at the knee during walking.
AB  - PURPOSE: In vivo measurement of the forces and strains in human tissues is
      currently impracticable. Computer modeling and simulation allows estimates of
      these quantities to be obtained noninvasively. This paper reviews our recent work
      on muscle, ligament, and joint loading at the knee during gait. METHODS: Muscle
      and ground-reaction forces obtained from a sophisticated computer simulation of
      walking were input into a detailed model of the lower limb to obtain ligament and
      joint-contact loading at the knee for one full cycle of gait. RESULTS: Peak
      anterior cruciate ligament (ACL) force occurred in early stance and was mainly
      determined by the anterior pull of the patellar tendon on the tibia. The medial
      collateral ligament was the primary restraint to anterior tibial translation
      (ATT) in the ACL-deficient knee. ATT in the ACL-deficient knee can be reduced to
      the level calculated for the intact knee by increasing hamstrings muscle force.
      Reducing quadriceps force was insufficient to restore ATT to the level calculated
      for the intact knee. For both normal and ACL-deficient walking, the resultant
      force acting between the femur and tibia remained mainly on the medial side of
      the knee. The knee adductor moment was resisted by a combination of muscle and
      ligament forces. CONCLUSION: Knee-ligament loading during the stance phase of
      gait is explained by the pattern of anterior shear force applied to the leg. The
      distribution of force at the tibiofemoral joint is determined by the variation in
      the external adductor moment applied at the knee. The forces acting at the
      tibiofemoral and patellofemoral joints are similar during normal and ACL
      deficient gait. Hamstrings facilitation is more effective than quadriceps
      avoidance in reducing ATT during ACL-deficient gait.

PMID- 16286867
TI  - Changes in athlete burnout and motivation over a 12-week league tournament.
AB  - INTRODUCTION: To date, empirical reports of an association between motivation and
      athlete burnout have been exclusively based on cross-sectional research.
      Conclusions regarding the nature of the relationship between motivation and
      burnout are limited because they do not provide longitudinal information.
      PURPOSE: To examine the relationship between burnout and motivation across a 12
      wk league tournament (pretournament, midtournament, and end of tournament).
      METHOD: Data were collected on using the Athlete Burnout Questionnaire and Sport
      Motivation Scale from 102 adult professional male rugby players at three
      different times during a 12-wk league tournament. RESULTS: Linear mixed modeling
      was used to explore hypothesized relationships between individual key
      characteristics of burnout and factors/covariates across time. Within the models,
      amotivation, the least self-determined type of motivation, had a large positive
      association with key characteristics of burnout. Self-determined forms of
      motivation (i.e., intrinsic motivation) exhibited significant negative
      associations with burnout. Extrinsic motivation, proposed to exist between
      intrinsic and amotivation on the self-determination continuum, was negatively
      associated with sport devaluation and reduced accomplishment as well as
      positively associated with physical and emotional exhaustion. Other factors
      related to burnout within the analysis included time (pretournament, in
      tournament, and end of tournament), team membership, number of injuries, years of
      national domestic league experience, and win/loss history. CONCLUSIONS: Overall,
      the results reflect the burnout experience may vary over time and support the
      potential utility of a self-determination theory explanation of burnout.

PMID- 16286868
TI  - Aerobic fitness and neurocognitive function in healthy preadolescent children.
AB  - PURPOSE: We investigated the relationship between age, aerobic fitness, and
      cognitive function by comparing high- and low-fit preadolescent children and
      adults. METHOD: Twenty-four children (mean age = 9.6 yr) and 27 adults (mean age
      = 19.3 yr) were grouped according to their fitness (high, low) such that four
      approximately equal groups were compared. Fitness was assessed using the
      Fitnessgram test, and cognitive function was measured by neuroelectric and
      behavioral responses to a stimulus discrimination task. RESULTS: Adults exhibited
      greater P3 amplitude at Cz and Pz sites, and decreased amplitude at the Oz site
      compared with children. High-fit children had greater P3 amplitude compared with
      low-fit children and high- and low-fit adults. Further, adults had faster P3
      latency compared with children, and high-fit participants had faster P3 latency
      compared with low-fit participants at the Oz site. Adults exhibited faster
      reaction time than children; however, fitness interacted with age such that high
      fit children had faster reaction time than low-fit children. CONCLUSION: These
      findings suggest that fitness was positively associated with neuroelectric
      indices of attention and working memory, and response speed in children. Fitness
      was also associated with cognitive processing speed, but these findings were not
      age-specific. These data indicate that fitness may be related to better cognitive
      functioning in preadolescents and have implications for increasing cognitive
      health in children and adults.

PMID- 16286869
TI  - Effects of high- and moderate-intensity training on metabolism and repeated
      sprints.
AB  - PURPOSE: We compared the effects of high-intensity interval (HIT) and moderate
      intensity continuous (MIT) training (matched for total work) on changes in
      repeated-sprint ability (RSA) and muscle metabolism. METHODS: Pre- and
      posttraining, VO(2peak), lactate threshold (LT), and RSA (5 x 6-s sprints, every
      30 s) were assessed in 20 females. Before and immediately after the RSA test,
      muscle biopsies were taken from the vastus lateralis. Subjects were matched on
      RSA, randomly placed into the HIT (N = 10) or MIT (N = 10) group and performed 5
      wk (3 d.wk(-1)) of cycle training; performing either HIT (6-10, 2-min intervals
      at 120-140% LT) or MIT (continuous, 20-30 min at 80-95% LT). RESULTS: Both groups
      had significant improvements in VO(2peak) (10-12%; P < 0.05) and LT (8-10%; P <
      0.05), with no significant differences between them. Both groups also had
      significant increases in RSA total work (kJ) (P < 0.05), with a significantly
      greater increase following HIT than MIT (13 vs 8.5%, respectively; P < 0.05).
      There was a significant decrease in resting [ATP] and an increase in postexercise
      [La(-)](b) for both groups, but no significant differences between them. There
      were no significant changes in resting or postexercise [PCr], [Cr], muscle [La(
      )], or [H(+)] after the training period. CONCLUSIONS: When total work is matched,
      HIT results in greater improvements in RSA than MIT. This results from an
      improved ability to maintain performance during consecutive sprints, which is not
      explained by differences in work done during the first sprint, aerobic fitness or
      metabolite accumulation at the end of the sprints.

PMID- 16286870
TI  - Prior resistance training and sex influence muscle responses to arm suspension.
AB  - PURPOSE: The magnitude of atrophy and strength loss induced by partial or
      complete disuse of skeletal muscles varies greatly among individuals. Factors
      predisposing some individuals to more extreme responses have not been identified.
      The purpose of this investigation was to determine whether 1) level of activity
      before disuse or 2) sex differences influence the magnitude of atrophy and
      changes in muscle strength, endurance, and sense of muscular effort in response
      to 21 d of arm suspension. METHODS: Thirty-one individuals (18 women, 13 men)
      completed either 8 wk of resistance training (TRAINED group) or no training
      (UNTRAINED group) before 21 d of elbow muscle arm suspension achieved by having
      one arm in a sling tethered to the body by a swathe. Muscle volume was measured
      using serial magnetic resonance imaging (MRI) cross-sectional images. Functional
      measurements included maximal isometric force (MIF) for elbow flexion, one
      repetition maximum (1RM) for biceps curl, number of repetitions to fatigue at 50%
      of 1RM, and sense of muscular effort measured using a force-matching task.
      RESULTS: Flexor muscle volume decreased (P < 0.001) by -7.7 +/- 7.3% across all
      subjects. The decrease (P < 0.001) in flexor muscle volume was significant in men
      but not women. Arm suspension induced decreases (P < 0.001) in MIF and 1RM that
      did not differ across sex or training groups. The number of repetitions to
      fatigue decreased (P < 0.05) in the UNTRAINED but not TRAINED groups. No changes
      in sense of muscular effort were measured. CONCLUSION: The smaller initial muscle
      size or sex-specific factors attenuated muscle loss but not strength or endurance
      losses in females during disuse. Resistance training before disuse may attenuate
      the loss in muscular endurance.

PMID- 16286871
TI  - Protein ingestion prior to strength exercise affects blood hormones and
      metabolism.
AB  - PURPOSE: The effects of protein consumption before strength training session on
      blood hormones, energy metabolites, RER, and excess postexercise oxygen
      consumption (EPOC) were examined. METHODS: Ten resistance-trained young men
      consumed either a 25 g of whey and caseinate proteins (PROT) or a noncaloric
      placebo (P) in a liquid form 30 min before a heavy strength training session
      (STS) in a crossover design separated by at least 7 d. STS lasted 50 min and
      included 5 x 1 RM squats, 3 x 10 RM squats and 4 x 10 RM leg presses with 2-, 3-,
      and 2-min recoveries, respectively. A protein-carbohydrate supplement was
      consumed after STS in both trials. Venous blood samples were collected before,
      during, and after STS and oxygen consumption before and after STS. RESULTS: Serum
      growth hormone (GH), testosterone, and free fatty acids (FFA) were significantly
      (P < or = 0.05) higher in P compared with PROT 5 min after an STS. The calculated
      area under curve (AUC) of the serum insulin response during an STS was
      significantly (P < 0.001) higher in PROT compared with P. The EPOC value from 90
      to 120 min after an STS was significantly greater in the PROT condition compared
      with P (P = 0.01), and PROT treatment had a significantly higher RER 2 h
      postexercise (P = 0.04). The AUC of serum FFA during STS correlated significantly
      and negatively with RER 10-30 min after STS (r = -0.53, P = 0.02). CONCLUSIONS:
      Consuming 25 g of whey and caseinate proteins 30 min before an STS significantly
      decreases serum GH, testosterone, and FFA levels, and increases serum insulin
      during an STS. Furthermore, the pre-STS protein increased EPOC and RER
      significantly during 2-h recovery after STS.

PMID- 16286872
TI  - Multiple effects of caffeine on simulated high-intensity team-sport performance.
AB  - INTRODUCTION: Caffeine enhances performance of single bouts of endurance
      exercise, but its effects on repeated bouts typical of those in high-intensity
      team sports are unclear. PURPOSE: To investigate effects of caffeine in a
      performance test simulating physical and skill demands of a rugby union game.
      METHODS: The study was a double-blind, randomized, crossover design in which nine
      competitive male rugby players ingested either caffeine (6 mg.kg(-1) body mass)
      or placebo (dextrose) 70 min before performing a rugby test. Each test consisted
      of seven circuits in each of two 40-min halves with a 10-min half-time rest. Each
      circuit included stations for measurement of sprint time (two straight-line and
      three agility sprints), power generation in two consecutive drives, and accuracy
      for passing balls rapidly. Interstitial fluid was sampled transdermally by
      electrosonophoresis before ingestion of caffeine or placebo and then before
      testing, at half-time, and immediately after testing; samples were assayed
      chromatographically for caffeine and epinephrine concentrations. RESULTS: The
      effects of caffeine on mean performance (+/-90% confidence limits) over all 14
      circuits were: sprint speeds, 0.5% (+/-1.7%) through 2.9% (+/-1.3%); first-drive
      power, 5.0% (+/-2.5%); second-drive power, -1.2% (+/-6.8%); and passing accuracy,
      9.6% (+/-6.1%). The enhancements were mediated partly through a reduction of
      fatigue that developed throughout the test and partly by enhanced performance for
      some measures from the first circuit. Caffeine produced a 51% (+/-11%) increase
      in mean epinephrine concentration; correlations between individual changes in
      epinephrine concentration and changes in performance were mostly unclear, but
      there were some strong positive correlations with sprint speeds and a strong
      negative correlation with passing accuracy. CONCLUSION: Caffeine is likely to
      produce substantial enhancement of several aspects of high-intensity team-sport
      performance.

PMID- 16286873
TI  - Skinfold prediction equation for athletes developed using a four-component model.
AB  - INTRODUCTION: Skinfold (SKF) equations exist to predict percent body fat (%BF) in
      athletes; however, none have been derived from multicomponent model reference
      measures. PURPOSE: To develop and cross-validate a %BF prediction equation based
      on SKF in athletes using a four-component model as the reference measure.
      METHODS: Subjects were 132 collegiate athletes (20.7 +/- 2.0 yr; 78 males: 28
      black, 50 white; 54 females: 10 black, 44 white). Four-component model estimates
      of %BF (%BF4C) included measures of total body water from deuterium dilution,
      bone mineral by dual- energy x-ray absorptiometry (DXA), and body density by
      densitometry using underwater weighing. SKF measures included subscapular,
      triceps, chest, midaxillary, suprailiac, abdominal, and thigh sites (7SKF). A
      prediction equation was developed on 102 athletes using 7SKF, race, and gender as
      predictor variables. Cross-validation was performed on a representative holdout
      sample of 30 athletes. RESULTS: The equation cross-validated well (slope and
      intercept both not different (P > 0.05) from the line of identity (LOI); r(YY') =
      0.85, total error (TE) = 3.76%BF) and was better than the existing athlete SKF
      equations (intercept and slope both different from LOI (P < 0.01); r(YY') = 0.76,
      TE = 4.51%BF). Notably, a prediction equation developed using 3SKF sites
      (abdomen, thigh, and triceps) produced a similar accuracy (intercept and slope
      both not different from LOI (P > 0.05); r(YY') = 0.85, TE = 3.66%BF).
      CONCLUSIONS: The new 7SKF equation improved on SKF equations developed using
      densitometry. The final equation based on the whole sample was %BF' = 10.566 +
      0.12077*(7SKF) - 8.057*(gender) - 2.545*(race). Moreover, a 3SKF equation was
      comparable in accuracy to the 7SKF equation: BF' = 8.997 + 0.24658*(3SKF) -
      6.343*(gender) - 1.998*(race).

PMID- 16286874
TI  - Concussion (mild traumatic brain injury) and the team physician: a consensus
      statement.

PMID- 16286875
TI  - Intracerebral hemorrhage.
AB  - INTRODUCTION: Intracerebral hemorrhage (ICH) occurs from the rupture of small
      vessels into the brain parenchyma and accounts for approximately 10% of all
      strokes in the United States, and carries with it a significantly high morbidity
      and mortality. SUMMARY: This article reviews the course and management of ICH.
      The most common chronic vascular diseases that lead to ICH are chronic
      hypertension and cerebral amyloid angiopathy. Additional factors that predispose
      to ICH include vascular malformations, chronic alcohol use, hypocholesterolemia,
      and use of anticoagulant medications. The understanding of mechanisms leading to
      ICH has advanced significantly, but questions regarding site predilection and
      timing of spontaneous hemorrhage still remain. Management in the acute setting is
      first focused on reducing hematoma expansion. Although no specific therapy has
      yet been proven effective, promising agents, particularly recombinant Factor
      VIIa, are on the horizon. Subsequent care is focused on controlling hemostasis,
      hemodynamics, and intracranial pressure in efforts to minimize secondary brain
      injury. CONCLUSION: The morbidity and mortality associated with ICH remain high
      despite recent advances in our understanding of the clinical course of ICH. Novel
      preventive and acute treatment therapies are needed and may be on the horizon.

PMID- 16286876
TI  - Pediatric sleep-related breathing disorders and restless legs syndrome: how
      children are different.
AB  - Sleep-related breathing disorders and restless legs syndrome have traditionally
      been felt to affect primarily adults. Recent research suggests that these
      conditions are surprisingly common in children as well, and that clinical
      manifestations may differ considerably from those seen in adults. This review
      summarizes the clinical characteristics, epidemiology, pathophysiology, and
      treatment of sleep-related breathing disorders and restless legs syndrome in
      children. Particular emphasis is placed on recent research and on how the
      presentation and treatment of these conditions are different in children compared
      with adults.

PMID- 16286877
TI  - Weakness in the ICU: Guillain-Barre syndrome, myasthenia gravis, and critical
      illness polyneuropathy/myopathy.
AB  - BACKGROUND: Weakness in the ICU may be caused by a number of disorders. Guillain
      Barre syndrome (GBS) and myasthenia gravis (MG) are examples of conditions that
      might lead to an ICU admission. The most likely cause of weakness after ICU
      admission is critical illness polyneuropathy/myopathy (CIP/M). REVIEW SUMMARY:
      Studies have attempted to determine both clinical and pulmonary function criteria
      for the proper timing of intubation in severe GBS and MG. Optimizing medical
      management of patients with GBS, MG, and CIP/M is essential in reducing the high
      morbidity and mortality associated with these conditions. This includes measures
      to prevent deep venous thrombosis, gastric and decubitus ulcer prophylaxis, and
      chest physiotherapy. Both intravenous immunoglobulin (IVIG) and therapeutic
      plasma exchange (TPE) are probably equal in efficacy for the treatment of GBS,
      although relapse rates may differ. Treatment of MG crisis with TPE or IVIG must
      be followed by long-term immunosuppression. Studies suggest possible preventative
      measures for CIP/M such as tighter glycemic control but there are still no
      definitive treatments. CONCLUSION: Research to advance our knowledge of the
      pathogenesis of GBS, MG, and CIP/M is clearly needed to develop more specific and
      more effective treatments in the future. In the meantime, measures that optimize
      medical management can be instituted to improve outcomes in patients with these
      conditions, preferably in a specialized neuroscience ICU setting.

PMID- 16286878
TI  - The clinical features, diagnosis, and prognosis of nonconvulsive status
      epilepticus.
AB  - Nonconvulsive status epilepticus (NCSE) is a state of ongoing seizure activity
      for at least 30 minutes, with cognitive or behavioral changes, but without
      convulsive clinical manifestations. It requires EEG for confirmation. It has been
      categorized into groups having focal or generalized EEG epileptic activity; and
      by etiology and level of consciousness (which predict outcome). Points of
      contention include the evolving definition of what constitutes NCSE, various
      reasons for a delayed, missed, or misidentified diagnosis, and the optimal
      management of these conditions.

PMID- 16286879
TI  - 10 questions about temozolomide and the treatment of brain tumors.

PMID- 16286881
TI  - Optic neuritis.

PMID- 16286884
TI  - Extended indications in living-donor liver transplantation: bile duct cancer.
AB  - The advantages of living donor liver transplantation are an individually
      available graft and a tremendously reduced waiting time until transplantation.
      One consequence is that many centers have extended the pretransplant selection
      criteria, especially for potential recipients suffering from hepatocellular
      carcinoma. In contrast, reports on living donor liver transplantation for
      cholangiocarcinoma are restricted to few case reports. We have analyzed our
      experience with seven patients suffering from cholangiocarcinoma (Klatskin
      tumors, n=5; intrahepatic cholangiocarcinoma, n=2). During a median follow-up of
      20 months (range 2-46 months), all patients are alive except for one
      posttransplant death. Four patients suffering from Klatskin tumors are alive
      without recurrence; both patients suffering from intrahepatic cholangiocarcinoma
      are alive with bone and peritoneal metastases. Living donor liver transplantation
      may be beneficial in selected patients suffering from Klatskin tumors, whereas
      caution should prevail when considering intrahepatic cholangiocarcinoma.

PMID- 16286885
TI  - Liver transplantation for hepatocellular carcinoma: is there evidence for
      expanding the selection criteria?
AB  - A consequent application of the Milan criteria in patients undergoing liver
      transplantation for hepatocellular carcinoma (HCC) may lead to excellent long
      term survival and a low incidence of recurrence. Expanding the selection criteria
      will result in more patients with hepatocellular carcinoma being potentially
      curative treated, but this approach is associated with at least a higher
      incidence of recurrence. Kaplan-Meier analysis of 110 patients, who underwent
      liver transplantation for HCC in our institution between 1987 and 2004, showed a
      significant improvement in patient survival with time. A change in criteria for
      patient selection may have contributed to the improved outcome. In 28 of 110
      patients a recurrence of HCC was observed. In 82% of patients, who developed
      recurrence of carcinoma, the Milan criteria were not met. Dropout from the
      waiting list is common and several methods, including percutaneous ethanol
      injection, radiofrequency ablation, and chemoembolization, are used to prevent
      tumor progression and thus prevent dropout. As no randomized trials are available
      some uncertainty remains, whether these neoadjuvant procedures improve outcome.
      At present, there is no evidence that this approach enables expansion of the
      selection criteria. Hepatocellular carcinoma is a major indication for living
      related liver transplantation because the risk of dropout while waiting is
      negligible. Extension of the Milan criteria in the setting of living related
      liver transplantation may offer more patients a potentially curative treatment,
      without reducing the donor pool of organs for other patients on the waiting list
      with nonmalignant liver disease.

PMID- 16286886
TI  - Surgical treatment of primary hepatic epithelioid hemangioendothelioma.
AB  - Epithelioid hemangioendothelioma is a very rare tumor of vascular origin. It can
      develop in different tissues such as soft tissue, lung, or liver. Hepatic
      epithelioid hemangioendothelioma (HEH) mostly affects females. The malignant
      potential of HEH often remains unclear in the individual patient. It can range
      from benign hemangioma to malignant hemangioendotheliosarcoma. Here we present
      our experience with five patients with primary HEH, who were treated with
      curative intention in our department. All patients in our series with confirmed
      histological HEH did not show extrahepatic extension and consequently underwent
      surgical treatment. In three patients, liver transplantation (LTx) was performed
      (two cadaveric and one living related). In one patient, a right-sided
      hemihepatectomy with partial resection of the diaphragm was performed. One
      patient died while she was on the waiting list for LTx due to rapid tumor
      progression. Postoperative follow-up ranged from 1 to 13 years. No adjuvant
      chemotherapy was applied. Until now, no recurrence of local tumor or distant
      metastases could be observed during follow-up in our series. Early detection and
      surgical intervention in case of HEH can potentially offer curative treatment.
      The treatment of first choice appears to be radical liver resection. In our view,
      LTx represents a potentially important option for patients with a nonresectable
      tumor. Despite the long waiting time, its often unclear dignity, and a proven
      progressive growth pattern, living related LTx also plays a potentially important
      role. The 5-year overall survival rate of patients with HEH in the literature
      varies from 43% to 55%. Long-term survival of patients with HEH is significantly
      higher compared to other hepatic malignancies. The role of adjuvant therapy
      currently remains unclear.

PMID- 16286887
TI  - Hepatocellular carcinoma: interventional bridging to liver transplantation.
AB  - Hepatocellular carcinoma (HCC) is one of the most common solid cancers worldwide
      with surgery being considered the treatment of choice. However, it is limited in
      view of the hepatic dysfunction and high recurrence rates associated with the
      disease. Liver transplantation offers the advantage of both, eradicating the
      tumor and treating the underlying liver disease and is the only chance for cure
      in patients suffering from HCC. Survival is known to reach 70% after 5 years and
      recurrent tumor can be found in less than 20% provided transplantation is
      restricted to patients with single tumors < or =5 cm or three nodules <3 cm
      (Milan criteria). However, donor organs are limited and the time on the
      transplant waiting list is up to 6 or 12 months in Europe and the United States
      with up to 30-40% dropouts per year. It has been demonstrated that patients with
      untreated HCC while on the waiting list longer than 6-10 months do not have any
      benefit in survival after liver transplantation. Interventional treatment options
      such as transarterial chemoembolization and percutaneous ablation techniques
      documented promising results concerning the reduction of dropouts from the
      waiting list and the potential risk for recurrent tumor. Mortality and morbidity
      were considerably low when radiological interventions had been considered as
      bridging therapies for liver transplantation. Percutaneous therapies come along
      with tumoral seeding of 0.1% to 0.6%. Adjuvant treatment with TACE, PEI, and/ or
      RFA in T1- and T2-staged HCC resulted in tumor-free survival after
      transplantation of 95.2% after 4 years and intention-to-treat survival of 94%,
      85%, and 79% at 1, 2, and 3 years, respectively. Aggressive ablation therapy with
      a short transplant waiting time has the potential to optimize the use of liver
      transplantation for curative intent in selected cirrhotic HCC patients.
      Especially combined treatments seemed to play a key role in achieving complete
      tumor necrosis associated with improved disease-free survival after liver
      transplantation. In conclusion, no evidence based data exist in the literature
      supporting the efficacy of adjuvant interventional treatment modalities for HCC
      in patients awaiting liver transplantation. However, it has been shown that
      adjuvant (multimodal) interventional treatments seem a promising option for safe
      and effective bridging.

PMID- 16286888
TI  - Prevention of hepatitis B recurrence after liver transplantation.
AB  - The reults of orthotopic liver transplantation (OLT) for hepatitis B virus (HBV)
      related liver disease are significantly influenced by the HBV recurrence rate.
      Complete eradication of hepatitis B is rarely possible after liver
      transplantation and hepatic and extrahepatic reservoirs are a continuous latent
      source of HBV recurrence. Therefore an adequate prophylaxis is mandatory. By
      introduction of long term passive immunoprophylaxis the recurrence rate could be
      markedly reduced and survival rates significantly improved. Due to the approval
      of antiviral drugs, especially lamivudine as the first approved antiviral agent
      against HBV, new prophylactic options, including combination prophylaxis, have
      been introduced. This modern antiviral managemant improved the outcome of
      hepatitis B patients after liver transplantation. The Results after OLT are
      nowadays reported to be as good or in a recent UNOS database report even better
      than in non-HBV patients. The type of recommended prophylaxis has undergone
      modifications within the last years and is still subject to changes due to the
      ongoing development of antiviral agents. In addition, due to high costs of
      hepatitis immunoglobulin alternatives such as prophylaxis with nucleos(t)ide
      analogues or vaccination are increasingly investigated. In the following, current
      strategies of reinfection prophylaxis and future perspectives are reviewed.

PMID- 16286889
TI  - Treatment of hepatitis C virus reinfection after liver transplantation.
AB  - Most liver transplant recipients become reinfected with hepatitis C virus after
      OLT followed by allograft dysfunction, transplant cirrhosis and graft failure in
      a significant proportion of patients. Both in the pre-emptive prophylactic
      setting and in the treatment setting sustained virological response rates are
      poor compared to the precirrhotic hepatitis state. Patients with significant
      hepatitis should be always treated before developing cirrhosis or even with early
      cirrhosis. After transplantation pegylated interferon in combination with
      ribavirin is the most successful treatment opportunity to date, however the best
      time point and treatment duration as well as doses for pegylated interferons and
      rebavirin have to be defined.

PMID- 16286890
TI  - Recurrence of focal-segmental glomerulosclerosis in children after renal
      transplantation: clinical and genetic aspects.
AB  - Focal segmental glomerulosclerosis (FSGS) is the primary renal disease in
      approximately one-tenth of pediatric patients receiving a renal allograft.
      Recurrence of proteinuria after renal transplantation is observed in
      approximately 30% of patients and negatively impacts graft survival. Risk factors
      for recurrence are a chronological age <15 years at onset of the nephrotic
      syndrome and a rapid progression of the disease in the native kidneys leading to
      end-stage renal disease in less than 3 years. Mesangial proliferation in the
      native kidneys is also an important negative predictive factor for disease
      recurrence. With rapid recurrence of FSGS and loss of the allograft, further
      renal transplants also carry a high likelihood of FSGS recurrence. Different
      pathogenic factors have been discussed for the recurrence of proteinuria/FSGS in
      the transplanted kidney, especially the involvement of a proteinuric circulating
      factor, whose production seems to follow T-cell dysfunction. In the last decade,
      mutations in genes encoding podocyte proteins have been identified in different
      forms of hereditary FSGS. Mutations of NPHS2 were detected in 26-38% of familial
      autosomal recessive steroid-resistant NS (SRNS), 6-19% of sporadic cases of SRNS,
      and in few adult patients with FSGS. Large multicenter studies demonstrated that
      patients with two pathogenic NPHS2 mutations have a very low risk of recurring
      FSGS after renal transplantation, whereas patients with only one mutation
      presumably have a risk comparable to non-NPHS2 FSGS patients. The management of
      FSGS following renal transplantation remains controversial. Following the
      assumption of a putative permeability factor, several studies have suggested the
      efficacy of plasmapheresis in inducing remission, preferably in conjunction with
      high-dose cyclosporine A or cyclophosphamide. Prospective studies will be
      necessary to better evaluate different therapeutic approaches.

PMID- 16286891
TI  - Liver transplantation for inborn errors of metabolism.
AB  - Liver transplantation (LT) has become an accepted treatment for various hepatic
      based metabolic disorders. For diseases with hepatic origin but mainly
      extrahepatic manifestations, it can be regarded as a means of gene therapy.
      Depending on the underlying disease, optimal dietary and medicamentous treatment
      cannot reliably prevent periods of metabolic decompensation resulting in severe
      organ damage. In severe neonatal forms of urea cycle disorders, liver
      transplantation should be considered in early infancy. The same applies to
      propionic acidemia, although severe perioperative complications have been
      described. In methylmalonic aciduria, there is no consensus whether LT alone is
      prior to combined liver and kidney transplantation (LKT). Moreover, late
      neurologic complications can occur in some patients with propionic and
      methylmalonic acidemias. LT as well as LKT is discussed in primary hyperoxaluria.
      For patients with cystic fibrosis and biliary cirrhosis, LT has become an
      established treatment that may even improve pulmonary function. Careful
      individual decisions must be made in patients with mitochondrial disorders
      because of possible progressive neuromuscular involvement. In most hepatic-based
      metabolic disorders, restoration of only about 10% of the original enzyme
      activity is sufficient to warrant sufficient metabolic control.

PMID- 16286892
TI  - Living related liver transplantation: the ultimate technique to expand the donor
      pool?
AB  - Today, living donor liver transplantation (LDLT) is well established in many
      centers as a therapeutic method for end-stage liver disease. LDLT is an option
      for selected cases and is still under development. From the beginning of LDLT
      until now, many innovations have been presented and as a consequence both the
      surgical and medical complications in both donors and recipients reduced greatly.
      As a benefit, this procedure enriches the donor organ pool and reduces the
      imbalance between the scarcity of organ resource and organ demand; however, LDLT
      will not solve the problem of organ shortage. Because the modality of LDLT is
      still associated with morbidity and mortality of the donors, recipient's graft
      size match problems and substantial surgical complications, ethical issues of
      live organ donation must be discussed. Nevertheless, estimates of patient
      survival and complications in both donors and recipients should incorporate
      waiting time mortality. With this background, the extended indications for LDLT
      compared with cadaveric liver transplantation would have to be discussed in many
      cases. In this brief review, we focus on potential complications for both donors
      and recipients after adult-to-adult LDLT, discuss ethical problems and
      controversies with special interest on the perspective and potentials of this
      surgical method.

PMID- 16286894
TI  - Evolution of liver transplantation at the University of Heidelberg: interventions
      influencing patient referral.
AB  - In Heidelberg, liver transplantation was first performed in 1987. In this
      article, we report our experience with an interdisciplinary approach
      (intervention) to improve the internal and external acceptance of the liver
      transplantation program. Formation of a transplant team and interdisciplinary
      standard setting of pre-, peri-, and postoperative protocols significantly
      stimulated this process. Involvement of the referring doctors in patient's
      treatment by transferring competencies enhanced patients referral to our center
      and increased the numbers of patients on the waiting list, an indispensable
      factor for organ allocation by Eurotransplant and transplantation. Involvement of
      patient organizations increased patient acceptance in the program.

PMID- 16286893
TI  - Indications of mycophenolate mofetil in liver transplantation.
AB  - Mycophenolate mofetil (MMF) is approved for prophylaxis of acute rejection after
      kidney, heart, and liver transplantation as well as for pediatric patients after
      kidney transplantation. MMF, a noncompetitive inhibitor of inosine monophosphate
      dehydrogenase (IMPDH), blocks de novo purine synthesis which leads to an
      effective inhibition of proliferation selectively in T and B lymphocytes, smooth
      muscle cells, and fibroblasts. MMF shows additional effects with inhibition of
      the expression of activating and adhesion molecules on the surface of
      lymphocytes. The beneficial safety profile with distinct side effects compared to
      calcineurin inhibitors (CNI) enable efficacious combination with ciclosporin or
      tacrolimus as de novo therapy after liver transplantation. Furthermore, recent
      studies show the possibility to reduce CNI induced toxicities by adding MMF to
      primary immunosuppression. MMF is also used to enable early steroid withdrawal
      after liver transplantation. MMF can increase efficacy of immunosuppressive
      therapy and thereby support the treatment of steroid resistant acute rejections,
      chronic rejections and chronic graft dysfunction.

PMID- 16286895
TI  - Risk stratification in cardiac amyloidosis: novel approaches.
AB  - Amyloidosis is a term for diseases with extracellular deposition of insoluble
      beta-fibrillar proteins in different organs. The heart is primarily involved in
      more than half of patients with immunoglobulin light-chain amyloidosis or
      hereditary amyloidosis and associated with poor prognosis. Different traditional
      diagnostic tools that have been described for risk stratification lack of
      sufficient sensitivity and specificity for patient survival. Until November 2004
      in 50 consecutive patients with light chain amyloidosis and 15 patients with
      hereditary amyloidosis electrocardiography, echocardiography, Holter monitoring,
      cardiopulmonary exercise test, lung function testing, tilt-test, and laboratory
      investigations have been performed at our department. Cardiac amyloidosis was
      found in 32 patients. Interventricular septum (14.3+/-0.5 mm vs. 12.3+/-0.7 mm,
      P<0.05), plasma NT-proBNP (7154+/-2122 ng/l vs. 380+/-113 ng/l; P<0.01), cardiac
      Troponin T (0.105+/-0.030 vs. 0.019+/-0.010 microg/l; P<0.05) were increased in
      patients with cardiac amyloidosis as compared to patients light chain amyloidosis
      but no cardiac involvement. Maximal inspiratory (Pimax) and expiratory (Pemax)
      mouth pressure were decreased with CA compared to controls. Correlation of NT
      proBNP and interventricular septum thickness (r=0.53, P=0.029) as well as and
      Pimax (r=0.72, P<0.01) or Pemax (r=0.69; P<0.01) was noticed. A correlation of
      grade of arrhythmias in Holter monitoring and syncopes was not observed. Cardiac
      involvement of amyloid disease carries a poor prognosis and is not well
      characterized by classic heart failure determinants. Heart transplantation based
      on novel risk markers including NT-proBNP might be a suitable therapeutic
      approach for patients with manifest cardiac amyloidosis, but will require
      alternative patient selection and listing criteria.

PMID- 16286896
TI  - Indications for liver transplantation in patients with amyloidosis: a single
      center experience with 11 cases.
AB  - Familial amyloidotic polyneuropathy (FAP) is an inherited disorder with the
      systemic deposition of amyloid fibrils containing mutant transthyretin variants.
      The mutant form of transthyretin amyloidosis is produced mainly in the liver.
      Successful liver transplantation (LTx) could eliminate the source of the variant
      transthyretin molecule, and is now the only known curative treatment. The aim of
      this study is to evaluate the results of LTx for FAP at the University of
      Heidelberg. Eleven patients who underwent LTx between 1985 and 2004 with the
      diagnosis of FAP were evaluated. Of 11 patients, seven (64%) were male and four
      (36%) were female. The mean age was 49.5 years (range 27-70). Met 30 (n=5) was
      the most common type of amyloidosis followed by Arg 50 (n=3), Val 107 (n=2), and
      Phe 33 (n=1). All of the patients were selected for LTx and Domino LTx was
      performed in six patients. The majority (80%) of the patients with type Met 30
      amyloidosis are alive, whereas in other types of amyloidosis only 33% are living.
      This finding emphasizes better prognosis of Met 30 variant of FAP in comparison
      to other variants such as Arg 50, Val 107, and Phe 33. After LTx, improvement of
      clinical symptoms (completely or partially) was observed in six patients (55%).
      In conclusion, LTx is considered as the only therapeutic alternative in patients
      with amyloidosis accompanied by hepatic synthesis of the amyloid protein. The
      most important risk factors for LTx can be predicted by assessing the nutritional
      condition of the patient, the duration of the disease, and the amyloid variant.
      Therefore, precise diagnostic measures are required before listing a patient for
      LTx. Domino LTx is an acceptable form of LTx that can preserve the pool of organ
      donors. In order to stop the progression of FAP, LTx would be justified in a
      subgroup of patients with amyloidosis. Based on our results, we support the idea
      that the effectiveness of extended preoperative period before LTx or the
      transplantation of other transthyretin variants other than Met 30 is
      questionable.

PMID- 16286897
TI  - Indications for high-dose chemotherapy with autologous stem cell support in
      patients with systemic amyloid light chain amyloidosis.
AB  - Systemic amyloid light chain amyloidosis is a protein conformation disorder
      caused by a clonal plasma cell dyscrasia. Symptoms result from fibrillar
      extracellular deposits in kidney, heart, liver, gut, peripheral nervous system
      and other tissues. The deposits disrupt organ function and ultimately lead to
      death. The prognosis of systemic amyloid light chain (AL) amyloidosis is poor;
      less than 5% of all patients survive 10 years or longer. Using conventional
      chemotherapy, the median survival could be prolonged by 4 months. Treatment with
      high-dose melphalm (HDM) and autologous stem cell transplantation (ASCT) of
      selected patients has been shown to arrest and even to reverse the disease
      course. This procedure however remains controversial because treatment related
      mortality (TRM) in AL amyloidosis is substantially higher (15-40%) than in
      multiple myeloma (<5%). Here we review recent results of ASCT, eligibility
      criteria for HDM and report our own treatment results in 41 patients.

PMID- 16286898
TI  - Transmission of malignancy with solid organ transplants.
AB  - Donor-derived malignancy is found in about 0.02-0.2% of allograft recipients.
      With an increasing number of older donors, this problem will gain more relevance
      in the future. We wish to review the current literature on tumor transmission
      with solid organ transplants and focus on the consequences of an extension of the
      donor pool, such as by the use of donors with a history of cancer. Finally,
      suggestions are made for screening regimens for living as well as cadaveric
      donors to minimize the risk of inadvertent tumor transmission.

PMID- 16286899
TI  - Waiting time for patients with history of malignant disease before listing for
      organ transplantation.
AB  - With increasing age of patients listed for organ transplantation the issue of
      preexisting malignomas in remission becomes more relevant. Because
      immunosuppressive therapy is associated with a remarkable increase in malignant
      disease, the current notion is that a history of malignancy puts the patient at
      high risk for relapse after transplantation. However, there is little reliable
      evidence that immunosuppression uniformly alters the risk of a patient with
      malignancy in remission. Therefore, the choice of a waiting time may prevent the
      patient from getting his inevitable tumor relapse after transplantation. Whether
      or not the relapse results in a worse prognosis compared to non-transplanted
      patients is not clear, either. On the background of this incomplete knowledge the
      decision to list a patient with a history of malignancy needs to be an individual
      one, taking into account the prognosis of the particular tumor, stage and
      original extent of disease as well as the overall prognosis of the patient if
      transplantation is withheld. Waiting times listed for different tumor entities by
      scientific societies are helpful; however, sometimes the individual decision
      needs to deviate from these suggestions. The recommendations are based on the
      Cincinnati Transplant Tumor Registry collecting data on malignancies related to
      transplantation. Even in this worldwide registry the number of cases for most
      tumor entities is small and does by far not cover all stages of disease. These
      data are an important part of decision making in order to determine whether it is
      best for the patient to be listed for transplantation or not.

PMID- 16286900
TI  - mTOR inhibition and its effect on cancer in transplantation.
AB  - A considerable amount of data indicates that transplanted patients are at
      increased risk for de novo and recurrent cancer. Treatment of this population is
      difficult. It remains unclear if the immunosuppressive therapy should be
      continued, tapered or even stopped or if immunosuppressive drugs with
      antiproliferative properties have beneficial effects in this situation. In
      various models, mTOR-inhibitors were shown to have immunosuppressive and anti
      tumor effects. Here, we have reviewed the current literature trying to clarify if
      mTOR-inhibition brings advantages for the transplanted patients suffering from
      tumors.

PMID- 16286901
TI  - The ongoing need for innovation in transplant medicine and surgery.

PMID- 16286902
TI  - Cost distribution of orthotopic liver transplantation: single-center analysis
      under DRG-based reimbursement.
AB  - Costs of orthotopic liver transplantation (OLT) are influenced by multiple
      factors. Surgeons must be interested in determining the probability of meeting
      the projected cost averages. Costs of procedures, labor, drugs and
      pharmaceuticals, materials, and overhead costs of infrastructure were calculated
      during the primary stay in 38 consecutive patients undergoing OLT at a single
      center. Endpoint of cost aggregation was discharge from acute care. Costs per
      patient were grouped to plot the cost density distribution function. Mean cost of
      OLT was 49,000. Costs showed a large variation, ranging from 18,000 to 189,000
      per case. Most patients were grouped in the G-DRG-A01C split (n=31), which
      characterizes the least resource consumptive split. Costs of OLT were not
      normally distributed. There was a left-skewed beta-distribution of costs. Labor
      related costs were responsible for the largest cost fraction (mean 42.9%),
      whereas drugs and medication accounted for 24.9% on average. Most patients could
      be transplanted within cost groups below 50,000. The marked cost heterogeneity
      after OLT suggests that primarily medical comorbidities are of relevance for
      extraordinary resource consumption. A minimum number of transplants should be
      performed in single institutions to improve chances to financially counterbalance
      higher costs of individual cases under DRG-based reimbursement. Small programs
      have to bear increased risks of financial distortion. The asymmetry of cost
      distribution after OLT should be taken into account in future reimbursement
      regulations.

PMID- 16286903
TI  - Diagnosis of non-palpable breast cancer(image-detected breast cancer).

PMID- 16286904
TI  - Diagnostic assessment of nonpalpable breast cancer--the difference in diagnostic
      approach for the clinical treatment of breast cancer between the Japanese
      Guidelines and the National Comprehensive Cancer Network(USA)Guidelines.
AB  - The detection of non-palpating breast cancer might improve the survival of
      patients with whole breast cancer because it can be diagnosed at an early stage.
      Therefore, to standardize the quality of patient care, a published assessment
      guideline is necessary in a clinical setting. For this purpose, Japan and USA
      have independent guidelines with different approaches. ''The evidence-based
      guideline for clinical treatment of breast cancer'' that was published in June
      2005 by the Japanese breast cancer society, is the first set of integrated
      guidelines pertaining to breast cancer in Japan. These guidelines are presented
      in the research questions (RQ)format. This paper explains 7 RQs(out of 31 RQs)and
      also discusses the recommendations pertaining to the diagnosis of nonpalpable
      breast cancer. The National Comprehensive Cancer Network (NCCN; USA)guidelines,
      which are widely recognized as one of the most reliable guidelines based on
      published evidences, also contain the diagnostic assessment of asymptomatic
      patients with a negative physical examination. This paper discusses pros and cons
      of each of the above mentioned guidelines as well as their clinical application.
      It is necessary to use both the Japanese and NCCN guidelines while understanding
      the differences between the two.

PMID- 16286905
TI  - Mammographic screening for non-palpable breast cancer in Japan.
AB  - In Japan, mammography was endorsed for breast cancer screening in women aged 40
      and over by the Ministry of Health, Labor and Welfare in 2004. The spread of
      mammographic screening has caused an increase in the incidence of non-palpable
      breast cancer. Precision reading for mammography is necessary to detect non
      palpable breast cancer. When mass and focal asymmetric density is noted, it is
      important to analyze the density, density gradient, internal structure, margin
      and associated findings. Calcifications are classified by morphology and
      distribution mainly. It is necessary to distinguish secretor-type calcifications
      from necrotic-type calcifications. The Iwate Cancer Association performed a
      population-based screening program for breast cancer using mammography combined
      with clinical breast examination of 42,065 women in Iwate Prefecture from 1999 to
      2003. A total of 2,329(5.7%)women were recalled and the 112 cases(0.27%) of
      cancer were detected in 114 breasts. Of 114 breast cancers, 40 (35%) were non
      palpable and 74(65%) were palpable. The early breast cancer (stage 0 and I) rate
      of the non-palpable group was significantly higher than that of the palpable
      group (90% and 47%, p = 0.0003). The node-negative rate of the non-palpable group
      was significantly higher than that of the palpable group (92% and 68%, p =
      0.011). It is expected that mammographic screening will be expanded and that the
      mortality rate from breast cancer in Japan will decrease, as in Europe and the
      United States.

PMID- 16286906
TI  - Ultrasound (US) diagnosis of nonpalpable breast cancer.
AB  - BACKGROUND: Ultrasound (US) is a standard modality to diagnose breast diseases.
      To elucidate the usefulness of US in the diagnosis of nonpalpable breast cancers,
      we reviewed the cases that were treated at our institution. METHODS: Of the 106
      cancers that were operated upon at the Tsukuba University Hospital between
      February 2004 and March 2005, 12 cancers were nonpalpable. We reviewed their US
      findings, results of US-guided fine needle aspiration cytology (FNAC), core
      biopsy results, and histological diagnoses. RESULTS: On US, 9 tumors appeared as
      masses. The US observations were valuable, but a confirmatory diagnosis could not
      be made. US-guided FNAC was performed in 8 cases; malignancy was suspected in 6
      cases. US-guided core biopsy was performed in 9 cases, and it was diagnostic in 7
      cases. CONCLUSIONS: Nonpalpable breast cancers can be effectively detected by US,
      and the diagnosis can be confirmed by US-guided FNAC or core biopsy.

PMID- 16286907
TI  - Pathological aspects of core needle biopsy for non-palpable breast lesions.
AB  - Recently, the incidence of non-palpable or noninvasive breast cancer has
      increased. Consequently, criteria for choosing procedures to obtain pathological
      materials had changed. Fine needle aspiration biopsy cytology (FNA) and core
      needle biopsy (CNB) are both reliable procedures for detecting breast cancer.
      However, for non-palpable lesions, the diagnostic accuracy of CNB is higher. The
      main limits of FNA are the high rate of insufficient sampling and inability to
      determine invasiveness. CNB is an established alternative to surgical biopsy, and
      CNB can avoid excess surgical biopsies in a large number of patients. In addition
      to accurate histological diagnosis, there is interest in obtaining prognostic
      information from CNB, especially for patients being considered for preoperative
      (neoadjuvant) therapy. CNB provides useful information about histologic type and
      grade. However, an unavoidable problem of CNB is underestimation of invasion. On
      the other hand, there is good concordance in particular for estrogen receptor
      (ER) and progesterone receptor (PR) between CNB and surgical excision. Several
      aspects of CNB remains controversial, such as diagnosing papillary lesions by
      CNB, problems regarding tumor cell displacement after CNB, and management of
      lobular neoplasia (LN) on CNB.

PMID- 16286909
TI  - Pathophysiology of seroma in breast cancer.
AB  - PURPOSE: Seroma is the most common complication of mastectomy. The aim of this
      systematic review is to clarify the pathophysiology of seroma. MATERIALS AND
      METHODS: A computer-assisted MEDLINE search was conducted, and additional
      references were found in the bibliographies of these articles. The reference
      terms ''breast cancer'', ''mastectomy'', ''seroma'', ''lymphocele'' and
      ''lymphocyst'' were used as both keyword and subject terms. The search was
      limited to studies published in English. RESULTS: The definition of seroma was
      highly variable across studies, but was most commonly a seroma large enough to be
      noticed by the patient or medical staff and affecting the patient's satisfaction
      in the immediate or acute postoperative period. So far, only limited data are
      available on the severity of seroma. With respect to the pathophysiology of
      seroma, the data indicated that several anatomical factors, especially dead
      space, likely contribute to seroma formation. However, it was obscure whether
      seroma was due to lymph-like fluid or exudate. CONCLUSION: There is considerable
      variability in the way seroma is defined across studies, and its pathophysiology
      remains uncertain.

PMID- 16286908
TI  - Mild cognitive impairment after adjuvant chemotherapy in breast cancer patients-
      evaluation of appropriate research design and methodology to measure symptoms.
AB  - The development of new chemotherapeutic agents and regimens has contributed to
      reduced risk of cancer recurrence and prolonged patient survival. However, mild
      cognitive impairment (MCI), also known as ''chemofog'' or ''chemobrain''
      following adjuvant chemotherapy for breast cancer has been reported since the
      late 1980s. Unfortunately, little is known about it's mechanism, type, severity,
      and episode length. This article reviewed related studies on the subject, and
      found that chemotherapy-induced MCI appears to occur in 10-40% of patients, and
      memory loss and lack of concentration are the most frequent symptoms. The
      symptoms are apparently transient, but take at least several years to disappear.
      Reviewed studies show a lack of clear understanding of what causes MCI directly.
      There is also a lack of consistency in symptom measurement. We point to the need
      to conduct well-designed studies which begin with a proper hypothesis. Future
      research needs to be randomized and longitudinal with a base measurement point
      before the chemotherapy cycle starts. Future studies must adopt an effective and
      sensitive method to measure MCI. The latest imaging technique, positron emission
      tomography (PET) may be a powerful tool. Also, all confounding factors, such as
      age, education, intelligence quotient (IQ), fatigue and depression, hormonal
      therapy and other treatments should be controlled within the study design. It is
      hoped that the results of such future studies will allow medical professionals to
      contemplate effective prevention, treatment and rehabilitation for MCI.

PMID- 16286910
TI  - HER-2/neu expression in locally advanced breast carcinomas: pre-and post
      neoadjuvant chemotherapy.
AB  - Clinical studies have shown a correlation of HER-2/neu amplification/over
      expression and favorable response to neoadjuvant chemotherapy and anti-HER-2/neu
      antibody treatment. However, contradictory findings also have been reported. Some
      tumors may develop resistance to neoadjuvant chemotherapy after an initial period
      of sensitivity. Our study attempts to evaluate the effects of neoadjuvant
      chemotherapy on HER-2/neu status in locally advanced breast cancer. Thirty-nine
      patients with locally advanced breast cancers established by core needle biopsy
      received neoadjuvant chemotherapy and were compared with 60 patients with breast
      cancers who did not receive neoadjuvant chemotherapy. IHC for HER-2/neu was
      performed on paraffin sections of the core biopsy before treatment and the
      excised specimen following chemotherapy and scored as Negative (0-1+), 2+ and 3+.
      The results of the study and the controls were compared and analyzed using
      Fisher's exact test. HER-2/neu IHC scores decreased in 28.5% (15/39) of patients
      receiving neo-adjuvant chemotherapy compared to 11.7% (7/60) of patients in the
      control (p < 0.013). HER-2/neu IHC status changed from strongly positive to
      negative (3+ to 0) in five of 39 (12.5%) in the study group and in 2 of 60 (3.3%)
      in control group (p = 0.104). For patients receiving neoadjuvant chemotherapy in
      whom the tumor becomes refractory to chemotherapy or recurs, repeat testing for
      HER-2/neu status may be necessary. Elimination of HER-2/neu positive tumor cells
      may account for the changes in the IHC scores and the development of resistance
      to neoadjuvant chemotherapy.

PMID- 16286911
TI  - Ultrasonographic findings of invasive lobular carcinoma differentiation of
      invasive lobular carcinoma from invasive ductal carcinoma by ultrasonography.
AB  - BACKGROUND: Although controversy exists, invasive lobular carcinoma (ILC) differs
      in its high frequency of microscopically positive margins after conservative
      therapy compared to invasive ductal carcinoma (IDC). If ILC could be recognized
      by imaging modalities, it would provide important information for surgeons. We
      tried to confirm whether it is possible to distinguish ILC from other invasive
      carcinomas by ultrasonography (US). METHODS: A total of 81 histologically
      confirmed cases of IDC, including 26 cases of papillotubular carcinoma, 28 cases
      of solid-tubular carcinoma and 27 cases of scirrhous carcinoma, as well as 24
      cases of ILC were selected and retrospectively studied with regard to the
      features of mass lesions on US examination. RESULTS: The sensitivities of US for
      papillotubular carcinoma, solid-tubular carcinoma, scirrhous carcinoma and ILC
      were 88.5%, 100%, 92.6% and 91.7% respectively. We could divide invasive breast
      cancer into two groups by US findings. One group had a low frequency of malignant
      findings and consisted of papillotubular and solid-tubular carcinomas, and the
      other group had a high frequency of malignant findings and consisted of scirrhous
      carcinomas and ILC. However, there were no statistical differences between
      papillotubular carcinoma and solid-tubular carcinoma or between scirrhous
      carcinoma and ILC with regard to the US findings. CONCLUSIONS: Scirrhous
      carcinoma, the most common type of IDC, and ILC are difficult to distinguish by
      US. Therefore it is difficult to separate ILC from IDC by US.

PMID- 16286912
TI  - Prospective evaluation of pectoralis muscle invasion of breast cancer by MR
      imaging.
AB  - BACKGROUND: Assessment of pectoralis muscle invasion is important for treatment
      planning for breast cancer. We evaluated the usefulness of breast magnetic
      resonance (MR) imaging for the detection of tumor invasion of the pectoralis
      muscle in breast cancer patients. MATERIALS AND METHODS: A total of 306 breast MR
      examinations were performed preoperatively. Three-dimensional gradient echo
      sequences, at a section thickness of 1.5 or 2 mm were obtained with
      administration of gadolinium-DTPA. All patients underwent surgery. RESULTS: In 33
      breasts, disruption of the fat plane between tumor and muscle was noted. Seven of
      33 cases showed muscle enhancement contiguous to enhanced tumors. Pathology
      reports indicated that 5 of 7 of the tumors involved muscle invasion. Of the 2
      false positive cases, one showed muscle enhancement because of a previous biopsy,
      and the other was incorrectly interpreted as showing muscle enhancement. Of the
      26 breasts which did not demonstrate muscle enhancement, none were found at
      surgery to have tumor involvement. CONCLUSION: Enhancement of the pectoralis
      muscle correlates well with muscle invasion, but there are a few potential
      pitfalls. Disruption of the fat plane between tumor and muscle, without muscle
      enhancement, might not indicate tumor involvement of the pectoralis muscle.

PMID- 16286913
TI  - Magnetic resonance-guided percutaneous microwave coagulation therapy for liver
      metastases of breast cancer in a case.
AB  - Real-time magnetic resonance (MR) imaging enables the application of percutaneous
      microwave coagulation for high-risk patients with metastatic liver tumours. The
      tumours, local vessels and bile ducts can be observed clearly in three
      dimensional sections and a sufficient surgical margin can be confirmed on the MR
      image even during the coagulation procedure. MR-guided percutaneous microwave
      coagulation therapy is effective for treatment of not only primary liver tumours
      but also metastatic breast cancers in the liver, which are not diffuse but
      discrete, and difficult to treat with only chemo-and endocrine therapy. We report
      a 44-year-old Japanese woman who underwent modified radical mastectomy for right
      breast cancer (T1c N0 M0 Stage I). Three years after the operation, she developed
      two metastatic liver tumours and was treated by MR-guided percutaneous microwave
      coagulation, achieving a complete response (CR) without any recurrence for 15
      months as of the present. The most beneficial aspect of MR-guided percutaneous
      microwave coagulation is its safety. It is only minimally invasive and can be
      repeated. This therapy, therefore promises to prolong the disease free period.
      Additional clinical trials will be valuable to delineate the effectiveness and
      safety of MR-guided percutaneous microwave coagulation therapy for controlling
      the liver metastases of breast cancer.

PMID- 16286914
TI  - A case of phyllodes tumor of the breast with a lesion mimicking fibroadenoma.
AB  - We report a case of phyllodes tumor (PT) with multiple lesions partly mimicking
      fibroadenoma (FA). A 43-year-old woman was referred to our institute because of a
      left breast mass which was diagnosed as FA clinically. During the follow-up, the
      mass gradually enlarged and excisional biopsy was performed to rule out malignant
      lesion. On histological examination, the tumor consisted of three different
      components; a lesion diagnosed as FA, another lesion as benign PT, and the other
      lesion as borderline PT. Finally, the tumor was diagnosed as borderline PT.
      Stromal cellularity may vary from area to area in any given PT. If there are some
      disagreements among the findings of imagings and cytology for the diagnosis of
      FA, as was seen in our case, the possibility of coexistence of PT should be
      considered.

PMID- 16286915
TI  - Synchronous liver metastases of intracystic papillary carcinoma with invasion of
      the breast.
AB  - A rare case of intracystic papillary carcinoma (IPC) with invasion had
      synchronous metastases to the liver at presentation. A 57-year-old postmenopausal
      woman noticed a right breast tumor 7 months prior to admission. Mammography
      showed an oval mass measuring 3.1 cm in diameter with no calcification, and
      ultrasonography showed an intracystic tumor with a papillary growth pattern. Fine
      needle aspiration cytology revealed adenocarcinoma. Excisional biopsy revealed
      intracystic solid papillary carcinoma with invasion. The tumor was a clear-cell
      type with extracellular mucin. Two months after the initial biopsy, a screening
      ultrasonographic examination of the liver showed multiple hyperechoic masses.
      Abdominal contrast-enhanced CT scan and magnetic resonance imaging (MRI) showed
      multiple hypervascular masses compatible with metastatic tumors. No suspicious
      lesions were detected on examinations for malignancy in other organs. Distant
      metastases in cases of IPC with invasion are very rare. The potential of distant
      metastasis in IPC with invasion and the difficulty of evaluating invasive foci
      should be recognized. Careful evaluation of distant metastases is recommended.

PMID- 16286916
TI  - Nodular pseudoangiomatous stromal hyperplasia of mammary stroma in a case showing
      rapid tumor growth.
AB  - Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon benign breast disease
      that presents as a localized breast mass. Breast tissue affected by PASH is
      characterized by a dense, collagenous proliferation of mammary stroma, forming
      interanastomosing capillary-like spaces. The importance of this benign lesion
      lies in distinguishing it from low grade angiosarcoma. We report a case of a 38
      year-old woman who presented with a rapidly growing breast tumor. She visited our
      hospital with a complaint of a painless right breast mass. Physical examination
      revealed a 3.6 x 2.2 cm, oval, elastic-firm, well-defined and easily movable
      mass. Mammograms revealed no discrete mass or calcifications. Sonographic
      examination revealed a 3.5 x 2.5 x 2.2 cm, oval, well-defined and homogenous
      hypoechoic mass without a cyst. A fine-needle aspiration sample of the breast
      mass showed some clusters of epithelial cells with small papillary structures and
      many scattered stromal cells with naked nuclei. Based on these findings, a
      provisional diagnosis of fibroadenoma was made and the patient was followed up.
      One year after the first visit, the mass enlarged rapidly and a follow-up
      mammogram revealed an 8.2 x 5.5 cm circumscribed mass without calcifications.
      Given the history of rapid growth of the mass, tumor excision was performed. The
      excised tumor was well demarcated and had a smooth external surface. Histologic
      examination revealed normal breast ducts and lobules, and specific proliferative
      epithelial changes were not seen. The lobular and duct structure of the breast
      parenchyma were separated by an increased amount of stroma. The fibrous stroma
      contained numerous anastomosing slit-like spaces. Isolated spindle cells appeared
      intermittently at the margins of the spaces resembled endothelial cells.
      Immunohistochemical staining showed that endothelial cells lining true blood
      vessels were positive for Factor VIII-related antigen, but the spindle cells were
      negative for Factor VIII. Pseudoangiomatous stromal hyperplasia was diagnosed.

PMID- 16286917
TI  - A case of non-metastatic giant mucinous carcinoma of the breast.
AB  - A surgically resected case of giant mucinous carcinoma of the breast that had
      remained untreated for 2 years is reported. A 64-year-old postmenopausal woman
      presented with a large right breast mass (17.4 x 16.5 x 14.5 cm). Although she
      had noticed a mass in the right breast 2 years previously, she had not sought
      treatment. Mucinous carcinoma was diagnosed by core needle biopsy and she
      underwent right modified radical mastectomy with a free skin graft. There were no
      lymph node metastases or distant metastases. Fourteen months postoperatively, she
      remains well without evidence of tumor recurrence. Although several reports have
      suggested that pure mucinous carcinoma of the breast has a favorable prognosis,
      we need to follow this case until the clinical behavior and the outcome become
      clear.

PMID- 16286918
TI  - A case of occult contralateral breast cancer incidentally detected by contrast
      enhanced MRI; report of a case with review of literature.
AB  - We encountered a case of occult contralateral breast cancer, previously
      undetected by conventional imaging such as mammography (MMG) and ultrasonography
      (US), but incidentally detected by contrast-enhanced magnetic resonance imaging
      (CE-MRI). We present it here with a review of the literature. A 67-year-old
      Japanese woman was referred to our hospital in October 2000 because of a 1.5 cm
      right breast lump detected in a medical checkup. MMG, US and fine needle
      aspiration cytology revealed a cancerous lesion during the right breast. No mass
      lesion was palpable nor was any detected by MMG or US in the left breast.
      Bilateral breast CE-MRI was performed for more detailed evaluation. Consequently,
      an occult contralateral breast cancerous lesion was detected incidentally by CE
      MRI, with the images showing rapid initial enhancement of time to signal
      intensity curves. Before surgery, bilateral breast lesions were diagnosed as
      invasive ductal carcinoma by open biopsy. She underwent bilateral breast
      conserving surgery with bilateral axillary lymph node dissection. The
      postoperative course was uneventful and no recurrence has been noted as of
      January 18th, 2004. CE-MRI of the contralateral breast should be of value as a
      routine screen in those patients with a known or suspected malignancy in one
      breast considering the limits of breast cancer detection by such conventional
      modalities as MMG and US.

PMID- 16286919
TI  - A Toll-like receptor-independent antiviral response induced by double-stranded B
      form DNA.
AB  - The innate immune system recognizes nucleic acids during infection or tissue
      damage; however, the mechanisms of intracellular recognition of DNA have not been
      fully elucidated. Here we show that intracellular administration of double
      stranded B-form DNA (B-DNA) triggered antiviral responses including production of
      type I interferons and chemokines independently of Toll-like receptors or the
      helicase RIG-I. B-DNA activated transcription factor IRF3 and the promoter of the
      gene encoding interferon-beta through a signaling pathway that required the
      kinases TBK1 and IKKi, whereas there was substantial activation of transcription
      factor NF-kappaB independent of both TBK and IKKi. IPS-1, an adaptor molecule
      linking RIG-I and TBK1, was involved in B-DNA-induced activation of interferon
      beta and NF-kappaB. B-DNA signaling by this pathway conferred resistance to viral
      infection in a way dependent on both TBK1 and IKKi. These results suggest that
      both TBK1 and IKKi are required for innate immune activation by B-DNA, which
      might be important in antiviral innate immunity and other DNA-associated immune
      disorders.

PMID- 16286921
TI  - Single-strand recombination signal sequence nicks in vivo: evidence for a capture
      model of synapsis.
AB  - Variable (diversity) joining (V(D)J) recombination is initiated by the
      introduction of single-strand DNA breaks (nicks) at recombination signal
      sequences (RSSs). The importance and fate of these RSS nicks for the regulation
      of the V(D)J rearrangement and their potential contribution to genomic
      instability are poorly understood. Using two new methodologies, we were able to
      detect and quantify specific RSS nicks introduced into genomic DNA by incubation
      with recombination-activating gene proteins in vitro. In vivo, however, we found
      that nicks mediated by recombination-activating gene (RAG) proteins were
      detectable only in gene segments associated with RSSs containing 12-base pair
      spacers but not in those containing 23-base pair spacers. These data support a
      model of capture rather than synapsis for pairwise RSS cleavage during V(D)J
      recombination.

PMID- 16286920
TI  - The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity.
AB  - Tim-3 is a T helper type 1 (T(H)1)-specific cell surface molecule that seems to
      regulate T(H)1 responses and the induction of peripheral tolerance. However, the
      identity of the Tim-3 ligand and the mechanism by which this ligand inhibits the
      function of effector T(H)1 cells remain unknown. Here we show that galectin-9 is
      the Tim-3 ligand. Galectin-9-induced intracellular calcium flux, aggregation and
      death of T(H)1 cells were Tim-3-dependent in vitro, and administration of
      galectin-9 in vivo resulted in selective loss of interferon-gamma-producing cells
      and suppression of T(H)1 autoimmunity. These data suggest that the Tim-3-galectin
      9 pathway may have evolved to ensure effective termination of effector T(H)1
      cells.

PMID- 16286922
TI  - Transgenic labeling of the corticospinal tract for monitoring axonal responses to
      spinal cord injury.
AB  - The rodent corticospinal tract (CST) has been used extensively to investigate
      regeneration and remodeling of central axons after injury. CST axons are
      currently visualized after injection of tracer dye, which is invasive, incomplete
      and prone to variation, and often does not show functionally crucial but
      numerically minor tract components. Here, we characterize transgenic mice in
      which CST fibers are specifically and completely labeled by yellow fluorescent
      protein (YFP). Using these CST-YFP mice, we show that minor CST components are
      responsible for most monosynaptic contacts onto motoneurons. Lesions of the main
      dorsal CST lead to extension of new collaterals, some of them originating from
      large, heavily myelinated axons within the minor dorsolateral and ventral CST
      components. Some of these new collaterals form additional direct synapses onto
      motoneurons. We propose that CST-YFP mice will be useful for evaluating
      strategies designed to maximize such remodeling and to promote regeneration.

PMID- 16286923
TI  - R-Ras is a global regulator of vascular regeneration that suppresses intimal
      hyperplasia and tumor angiogenesis.
AB  - R-Ras is a small GTPase of the Ras family that regulates cell survival and
      integrin activity. Despite a number of in vitro studies, the in vivo function of
      R-Ras remains unclear. Here, we used R-Ras-null mice to explore the in vivo
      function of this small GTPase. Our results show a role for R-Ras as a regulator
      of vascular differentiation that primarily affects the remodeling of blood
      vessels. We show that R-Ras-null mice, although otherwise phenotypically normal,
      mount excessive vascular responses. We found that in vivo R-Ras expression is
      largely confined to fully differentiated smooth muscle cells, including those of
      blood vessels, and to endothelial cells. Challenging the R-Ras-null mice with
      arterial injury or tumor implantation showed exaggerated neointimal thickening in
      response to the injury and increased angiogenesis in the tumors. In wild-type
      mice, R-Ras expression was greatly reduced in hyperplastic neointimal smooth
      muscle cells and in angiogenic endothelial cells. Forced expression of activated
      R-Ras suppressed mitogenic and invasive activities of growth factor-stimulated
      vascular cells. These results establish an unexpected role for R-Ras in blood
      vessel homeostasis and suggest that R-Ras signaling may offer a target for
      therapeutic intervention in vascular diseases.

PMID- 16286924
TI  - IKK mediates ischemia-induced neuronal death.
AB  - The IkappaB kinase complex IKK is a central component of the signaling cascade
      that controls NF-kappaB-dependent gene transcription. So far, its function in the
      brain is largely unknown. Here, we show that IKK is activated in a mouse model of
      stroke. To investigate the function of IKK in brain ischemia we generated mice
      that contain a targeted deletion of Ikbkb (which encodes IKK2) in mouse neurons
      and mice that express a dominant inhibitor of IKK in neurons. In both lines,
      inhibition of IKK activity markedly reduced infarct size. In contrast,
      constitutive activation of IKK2 enlarged the infarct size. A selective small
      molecule inhibitor of IKK mimicked the effect of genetic IKK inhibition in
      neurons, reducing the infarct volume and cell death in a therapeutic time window
      of 4.5 h. These data indicate a key function of IKK in ischemic brain damage and
      suggest a potential role for IKK inhibitors in stroke therapy.

PMID- 16286925
TI  - The antioxidant function of the p53 tumor suppressor.
AB  - It is widely accepted that the p53 tumor suppressor restricts abnormal cells by
      induction of growth arrest or by triggering apoptosis. Here we show that, in
      addition, p53 protects the genome from oxidation by reactive oxygen species
      (ROS), a major cause of DNA damage and genetic instability. In the absence of
      severe stresses, relatively low levels of p53 are sufficient for upregulation of
      several genes with antioxidant products, which is associated with a decrease in
      intracellular ROS. Downregulation of p53 results in excessive oxidation of DNA,
      increased mutation rate and karyotype instability, which are prevented by
      incubation with the antioxidant N-acetylcysteine (NAC). Dietary supplementation
      with NAC prevented frequent lymphomas characteristic of Trp53-knockout mice, and
      slowed the growth of lung cancer xenografts deficient in p53. Our results provide
      a new paradigm for a nonrestrictive tumor suppressor function of p53 and
      highlight the potential importance of antioxidants in the prophylaxis and
      treatment of cancer.

PMID- 16286926
TI  - FARP2 triggers signals for Sema3A-mediated axonal repulsion.
AB  - Sema3A, a prototypical semaphorin, acts as a chemorepellent or a chemoattractant
      for axons by activating a receptor complex comprising neuropilin-1 as the ligand
      binding subunit and plexin-A1 as the signal-transducing subunit. How the signals
      downstream of plexin-A1 are triggered upon Sema3A stimulation, however, is
      unknown. Here we show that, in the presence of neuropilin-1, the FERM domain
      containing guanine nucleotide exchange factor (GEF) FARP2 associates directly
      with plexin-A1. Sema3A binding to neuropilin-1 induces the dissociation of FARP2
      from plexin-A1, resulting in activation of FARP2's Rac GEF activity, Rnd1
      recruitment to plexin-A1, and downregulation of R-Ras. Simultaneously, the FERM
      domain of FARP2 sequesters phosphatidylinositol phosphate kinase type I isoform
      PIPKIgamma661 from talin, thereby inhibiting its kinase activity. These
      activities are required for Sema3A-mediated repulsion of outgrowing axons and
      suppression of neuronal adhesion. We therefore conclude that FARP2 is a key
      molecule involved in the response of neuronal growth cones to class-3
      semaphorins.

PMID- 16286927
TI  - Neural correlates of actual and predicted memory formation.
AB  - We aimed to discover the neural correlates of subjective judgments of learning
      whereby participants judge whether current experiences will be subsequently
      remembered or forgotten-and to compare these correlates to the neural correlates
      of actual memory formation. During event-related functional magnetic resonance
      imaging, participants viewed 350 scenes and predicted whether they would remember
      each scene in a later recognition-memory test. Activations in the medial temporal
      lobe were associated with actual encoding success (greater activation for
      objectively remembered than forgotten scenes), but not with predicted encoding
      success (activations did not differ for scenes predicted to be remembered versus
      forgotten). Conversely, activations in the ventromedial prefrontal cortex were
      associated with predicted but not actual encoding success, and correlated with
      individual differences in the accuracy of judgments of learning. Activations in
      the lateral and dorsomedial prefrontal cortex were associated with both actual
      and predicted encoding success. These findings indicate specific dissociations
      and associations between the neural systems that mediate actual and predicted
      memory formation.

PMID- 16286928
TI  - Cognitive control mechanisms resolve conflict through cortical amplification of
      task-relevant information.
AB  - A prominent model of how the brain regulates attention proposes that the anterior
      cingulate cortex monitors the occurrence of conflict between incompatible
      response tendencies and signals this information to a cognitive control system in
      dorsolateral prefrontal cortex. Cognitive control is thought to resolve conflict
      through the attentional biasing of perceptual processing, emphasizing task
      relevant stimulus information. It is not known, however, whether conflict
      resolution is mediated by amplifying neural representations of task-relevant
      information, inhibiting representations of task-irrelevant information, or both.
      Here we manipulated trial-by-trial levels of conflict and control during a Stroop
      task using face stimuli, while recording hemodynamic responses from human visual
      cortex specialized for face processing. We show that, in response to high
      conflict, cognitive control mechanisms enhance performance by transiently
      amplifying cortical responses to task-relevant information rather than by
      inhibiting responses to task-irrelevant information. These results implicate
      attentional target-feature amplification as the primary mechanism for conflict
      resolution through cognitive control.

PMID- 16286929
TI  - Neuronal correlates of subjective sensory experience.
AB  - When a near-threshold stimulus is presented, a sensory percept may or may not be
      produced. The unpredictable outcome of such perceptual judgment is believed to be
      determined by the activity of neurons in early sensory cortex. We analyzed the
      responses of neurons in primary somatosensory cortex, recorded while monkeys
      judged the presence or absence of threshold stimuli. We found that these
      responses did not covary with the monkeys' perceptual reports. In contrast, the
      activity of frontal lobe neurons did covary with trial-by-trial judgments.
      Further control and microstimulation experiments indicated that frontal lobe
      neurons are closely related to the monkeys' subjective experiences during sensory
      detection.

PMID- 16286930
TI  - NMDA receptor-independent long-term depression correlates with successful aging
      in rats.
AB  - Some individuals maintain high cognitive functioning at older ages. Here we show
      that mechanisms for long-term depression differ in aged rodents that maintain
      cognitive performance compared to young adults. Our results imply that cognitive
      abilities may be sustained in aged individuals by a switch in synaptic plasticity
      mechanisms.

PMID- 16286931
TI  - Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and
      Tsc2.
AB  - Mutations in the TSC1 or TSC2 tumor suppressor genes lead to tuberous sclerosis
      complex (TSC), a dominant hamartomatous disorder that often presents with mental
      retardation, epilepsy and autism. The etiology of these neurological symptoms is
      unclear and the function of the TSC pathway in neurons is unknown. We found that
      in post-mitotic, hippocampal pyramidal neurons of mice and rats, loss of Tsc1 or
      Tsc2 triggered enlargement of somas and dendritic spines and altered the
      properties of glutamatergic synapses. Furthermore, loss of a single copy of the
      Tsc1 gene was sufficient to perturb dendritic spine structure. Morphological
      changes required regulation of the actin-depolymerization factor cofilin at a
      conserved LIM-kinase phosphorylation site, the phosphorylation of which was
      increased by loss of Tsc2. Thus, the TSC pathway regulates growth and synapse
      function in neurons, and perturbations of neuronal structure and function are
      likely to contribute to the pathogenesis of the neurological symptoms of TSC.

PMID- 16286932
TI  - Uncertainty-based competition between prefrontal and dorsolateral striatal
      systems for behavioral control.
AB  - A broad range of neural and behavioral data suggests that the brain contains
      multiple systems for behavioral choice, including one associated with prefrontal
      cortex and another with dorsolateral striatum. However, such a surfeit of control
      raises an additional choice problem: how to arbitrate between the systems when
      they disagree. Here, we consider dual-action choice systems from a normative
      perspective, using the computational theory of reinforcement learning. We
      identify a key trade-off pitting computational simplicity against the flexible
      and statistically efficient use of experience. The trade-off is realized in a
      competition between the dorsolateral striatal and prefrontal systems. We suggest
      a Bayesian principle of arbitration between them according to uncertainty, so
      each controller is deployed when it should be most accurate. This provides a
      unifying account of a wealth of experimental evidence about the factors favoring
      dominance by either system.

PMID- 16286933
TI  - Independence of luminance and contrast in natural scenes and in the early visual
      system.
AB  - The early visual system is endowed with adaptive mechanisms that rapidly adjust
      gain and integration time based on the local luminance (mean intensity) and
      contrast (standard deviation of intensity relative to the mean). Here we show
      that these mechanisms are matched to the statistics of the environment. First, we
      measured the joint distribution of luminance and contrast in patches selected
      from natural images and found that luminance and contrast were statistically
      independent of each other. This independence did not hold for artificial images
      with matched spectral characteristics. Second, we characterized the effects of
      the adaptive mechanisms in lateral geniculate nucleus (LGN), the direct recipient
      of retinal outputs. We found that luminance gain control had the same effect at
      all contrasts and that contrast gain control had the same effect at all mean
      luminances. Thus, the adaptive mechanisms for luminance and contrast operate
      independently, reflecting the very independence encountered in natural images.

PMID- 16286934
TI  - Neural population coding of sound level adapts to stimulus statistics.
AB  - Mammals can hear sounds extending over a vast range of sound levels with
      remarkable accuracy. How auditory neurons code sound level over such a range is
      unclear; firing rates of individual neurons increase with sound level over only a
      very limited portion of the full range of hearing. We show that neurons in the
      auditory midbrain of the guinea pig adjust their responses to the mean, variance
      and more complex statistics of sound level distributions. We demonstrate that
      these adjustments improve the accuracy of the neural population code close to the
      region of most commonly occurring sound levels. This extends the range of sound
      levels that can be accurately encoded, fine-tuning hearing to the local acoustic
      environment.

PMID- 16286935
TI  - The Cbf5-Nop10 complex is a molecular bracket that organizes box H/ACA RNPs.
AB  - Box H/ACA ribonucleoprotein particles (RNPs) catalyze RNA pseudouridylation and
      direct processing of ribosomal RNA, and are essential architectural components of
      vertebrate telomerases. H/ACA RNPs comprise four proteins and a multihelical RNA.
      Two proteins, Cbf5 and Nop10, suffice for basal enzymatic activity in an archaeal
      in vitro system. We now report their cocrystal structure at 1.95-A resolution. We
      find that archaeal Cbf5 can assemble with yeast Nop10 and with human telomerase
      RNA, consistent with the high sequence identity of the RNP components between
      archaea and eukarya. Thus, the Cbf5-Nop10 architecture is phylogenetically
      conserved. The structure shows how Nop10 buttresses the active site of Cbf5, and
      it reveals two basic troughs that bidirectionally extend the active site cleft.
      Mutagenesis results implicate an adjacent basic patch in RNA binding. This
      tripartite RNA-binding surface may function as a molecular bracket that organizes
      the multihelical H/ACA and telomerase RNAs.

PMID- 16286937
TI  - Deaths from poisoning in New Zealand--new study helps identify and justify
      priorities for prevention.

PMID- 16286936
TI  - Older patients in the nephrology clinic--should they be referred?
AB  - AIM: To review the outcomes of elderly patients referred to a nephrology clinic
      and to develop referral guidelines. METHODS: A retrospective audit of patients
      aged 65 years or older referred over a 24-month period to a nephrology clinic.
      Outcomes assessed were whether a renal diagnosis was made and if there was any
      change in management. RESULTS: Sixty-one patients were referred with an average
      age of 74 years (range 65-88 years). The commonest reason for referral was renal
      impairment (69%); mean estimated creatinine clearance 32 ml/min. Diagnoses
      included hypertensive renal disease (30%), chronic renal failure - cause unknown
      (18%) and diabetic nephropathy (8%). In the majority of cases, the diagnosis was
      clinical. Renal biopsy was performed on four patients and declined by a further
      two. Management usually consisted of advice regarding clinical monitoring and
      drug treatment (80%). The clinic visit resulted in a change of management in 50%
      of cases. CONCLUSIONS: Most elderly patients with renal disease have chronic
      pathology for which intensive investigation is not warranted. The majority of
      nephrology clinic referrals resulted in advice on clinical management being given
      to the general practitioner. Patients with severe or acute renal impairment are
      more likely to be investigated and offered treatment. Referral guidelines for
      general practitioners may aid appropriate referral.

PMID- 16286938
TI  - Independent nurse prescribing in New Zealand.

PMID- 16286939
TI  - Deaths from poisoning in New Zealand: 2001-2002.
AB  - AIMS: To describe the epidemiology and toxicology of poisoning deaths in New
      Zealand for 2001 and 2002. METHODS: Poisoning mortality data for 2001 and 2002
      were collected from the Coronial Service Office (CSO) as part of the New Zealand
      chemical injury surveillance system. RESULTS: There was 235 and 234 poisoning
      deaths in 2001 and 2002 respectively, an annual rate of 6.3 [95% CI of 5.5 to
      7.1] deaths per 100,000 population for both years. Two-thirds (67.0%) of the
      deaths were intentional. The 25-44 year age group had the largest number of cases
      and highest age-specific rate (123 deaths, 11.1 [95% CI: 9.3-13.2] per 100,000 in
      2001 and 119 deaths, 10.7 [(95% CI: 9.0-12.8] per 100,000 in 2002). Over two
      thirds (68.9%) of the deaths were male. In 2001, the European rate was slightly
      higher than that for Maori but rates for the two ethnicities were similar in
      2002. Geographically, West Coast District Health Board (DHB) had the highest
      rates. Rates increased with increasing deprivation. Nearly two-thirds (64.3%) of
      the intentional deaths were attributed to carbon monoxide. Methadone, morphine or
      heroin, and ethanol were the leading causes of the unintentional deaths.
      CONCLUSIONS: The rate of poisoning deaths in New Zealand is comparable with other
      industrial countries as is the prominence of poisoning as a leading method of
      suicide.

PMID- 16286940
TI  - Increased rates of trimethoprim resistance in uncomplicated urinary tract
      infection: cause for concern?
AB  - AIMS: To assess changes in trimethoprim resistance over 2 years in bacteria
      causing uncomplicated urinary tract infections (UTIs) presenting to a
      representative group of general practitioners (GPs) in Christchurch. METHODS:
      Seventy-six randomly selected GPs in Christchurch (the Christchurch Sentinel
      network) participated in the study. Using the same methodology as in the
      previously reported 2000 collection, midstream urine (MSU) samples were
      prospectively collected for standard microbiological analysis on all women
      between the ages of 16 and 50 years presenting with symptoms of dysuria and
      frequency and who had positive dipstick testing for either nitrites, leucocytes,
      or both. MSUs were submitted for bacterial colony counts and resistance testing
      of isolates present in numbers >105 cfu/ml of urine. RESULTS: 216 dipstick
      positive specimens were collected in the survey period; 105 of these fulfilled
      criteria for significant bacteriuria. Trimethoprim resistance was found in 16
      (15.2%) overall, with a resistance rate for Escherichia coli (E. coli) to
      trimethoprim of 17.7%. When compared to the proportions of organisms resistant in
      the 2000 study, there were apparent but non significant increases in the total
      resistance among pathogens (+6.7%) and E. coli resistance (+5.8%). Rates of
      antibiotic resistance of all organisms to nitrofurantoin (2.9%) and norfloxacin
      (0.95%) remain low. There was a statistically significant increase in resistance
      among all women presenting with symptoms and a positive dipstick test (+5.3%; 95%
      CI: 1.5%-9.1%). For a woman in this age group presenting with symptoms of urinary
      tract infection and a positive dipstick test, we estimate that her probability of
      having a trimethoprim-resistant organism in 2002 was 7.4% compared with 2.7% in
      2000. CONCLUSION: Trimethoprim resistance of E. coli causing uncomplicated UTI
      appears to be rising in Christchurch. This may reflect the promotion and
      extensive use of this agent as first-line treatment. Whilst these data indicate
      that trimethoprim remains a reasonable first-line empiric treatment in this
      condition, this may change if trimethoprim resistance continues to rise. The
      apparent increase over a relatively short period (2-3 years) demonstrates the
      importance of regular surveillance. A third study is required to confirm whether
      this is a significant trend.

PMID- 16286941
TI  - Vitamin D deficiency among patients attending a central New Zealand rheumatology
      outpatient clinic.
AB  - AIMS: To measure the Vitamin D status in patients attending a rheumatology
      outpatient clinic because of the known musculoskeletal and immunosuppressive
      effects of Vitamin D deficiency. METHODS: 66 consecutive patients at a private
      rheumatology clinic in central New Zealand were recruited at the beginning of
      winter. RESULTS: Of 66 patients, 55 patients were included in the analysis. 43
      (78%) had 25OH cholecalciferol levels that were below the reference range (50-150
      nmol/L), and of these 12 (22%) had levels classified as moderate to severe
      deficiency (<25 nmol/L). CONCLUSIONS: Vitamin D deficiency is common in this
      setting, and is likely to contribute to the musculoskeletal symptoms experienced
      in this population.

PMID- 16286942
TI  - The case for lifelong follow-up after endovascular aneurysm repair.

PMID- 16286944
TI  - 'Woman bites dog'--making sense of media and research reports that claim women
      and men are equally violent.
AB  - The media are quick to exploit research reports that appear to show women and men
      are equally violent. Unfortunately, while such reports contradict the
      observations of experienced medical workers, police, court personnel, and Women's
      Refuge workers, they do influence public perceptions and may undermine policies
      designed to prevent and reduce male partner violence against women. This article
      examines research claims of women's equivalent violence and explains why study
      outcomes claiming equal violence must not be accepted at face value.

PMID- 16286945
TI  - Death due to butane abuse--the clinical pharmacology of inhalants.

PMID- 16286943
TI  - Dieulafoy lesion in the duodenum.

PMID- 16286946
TI  - What's happening in PHARMAC--where do all the submissions go? On the trail of
      gemcitabine.
AB  - The process and progress of submissions to PHARMAC for funding of new treatments
      is unclear. There appears to be a lack of communication or transparency regarding
      funding applications, decisions, or expected timelines to reach an endpoint. It
      is difficult to have confidence in a process that lacks such definition. A recent
      clinician submission for funding of an oncology treatment (gemcitabine) for
      bladder cancer highlights these issues.

PMID- 16286947
TI  - The Christchurch Tissue Bank to support cancer research.
AB  - AIM: To report on the development of a central resource of consented cancer
      tissues for researchers to use for ethically approved projects, and to describe
      the banking process. METHODS: The development of tissue banking in Christchurch,
      New Zealand is described, including the number and main types of samples
      collected. The consent forms have evolved with several new donor options added
      between 1996 and 2004. Since June 2004, disposal of tissues by a karakia
      (blessing) has been offered. Characteristics of each tissue including amount,
      location in the bank, and relevant clinicopathological data have been recorded
      prospectively in a detailed secure relational database. RESULTS: The changes in
      the consent form and donor options are described. Most donors (99.6%) consented
      to allow access to medical records (since May 2002); 98.3% to tissue being sent
      overseas (since May 2003), 97.4% to commercial research (since May 2003), and
      35.6% requested disposal with a karakia. Since May 2003, 87% of donors have been
      Caucasian, 5.1% Maori, and the remainder composed of other categories as stated
      on the 2001 New Zealand census format. By March 2005, samples have been banked
      from more than 2000 donors. For each of the last 4 years, samples have been
      collected from more than 300 donors, including fresh-frozen tissue, DNA
      preparations, serum, plasma, and paraffin blocks. The predominant tissues are
      from donors with cancers of the breast, colon, urological, and gynaecological
      sites. CONCLUSIONS: The Christchurch Tissue Bank is a successful model for
      potential New Zealand-wide application, providing quality tissue samples for
      cancer research whilst appropriately addressing ethical, legal, and cultural
      aspects of their collection.

PMID- 16286948
TI  - Medical image. Ampullary mass and obstructive jaundice.

PMID- 16286949
TI  - PHARMAC's response on gemcitabine and transparency.

PMID- 16286951
TI  - The advantages of notifying negative HIV results by telephone.

PMID- 16286950
TI  - PHARMAC responds on long-acting inhalers for COPD.

PMID- 16286952
TI  - Listeria--how much do pregnant women really understand about it?

PMID- 16286953
TI  - Merck responds to PHARMAC's article on COX-2 inhibitors.

PMID- 16286954
TI  - Synergistic effect of fosfomycin and fluoroquinolones against Pseudomonas
      aeruginosa growing in a biofilm.
AB  - Ulifloxacin is the active form of the prodrug prulifloxacin and shows a highly
      potent antipseudomonal activity. In this study, we examined the combined effect
      of fosfomycin and ulifloxacin against Pseudomonas aeruginosa (P. aeruginosa)
      growing in a biofilm using a modified Robbins device with artificial urine, and
      compared it to that of the combination of fosfomycin and ciprofloxacin or
      levofloxacin. An ATP bioluminescence assay was used to evaluate the antibacterial
      activity of the agents against sessile cells in a mature biofilm developed on a
      silicon disk. The total bioactivity of P. aeruginosa growing in a biofilm that
      had not been fully eradicated by fosfomycin or any of the fluoroquinolones alone
      at 10 times the MIC decreased after combination treatment with fosfomycin and
      fluoroquinolones. Morphological changes occurred in a time-dependent fashion;
      namely, swollen and/or rounding cells emerged within a couple of hours after
      combination treatment, marking the initial stage in the process leading to the
      destruction of the biofilms. We could not find any difference among the 3
      fluoroquinolones with regard to their synergistic effects when administered with
      fosfomycin. The combination treatment of fosfomycin and fluoroquinolones with
      highly potent antipseudomonal activities was effective in eradicating sessile
      cells of P. aeruginosa in the biofilm and promises to be beneficial against
      biofilm-associated infectious diseases.

PMID- 16286955
TI  - Lamivudine treatment in patients with HBV-related hepatocellular carcinoma--using
      an untreated, matched control cohort.
AB  - Lamivudine is widely used to treat patients with hepatitis B. However, the
      outcomes in patients with hepatocellular carcinoma (HCC) treated with lamivudine
      have not been established. This study was conducted to evaluate the outcomes of
      lamivudine treatment for patients with HCC using an untreated, matched control
      group. Thirty patients with controlled HCC orally received lamivudine. As
      controls, 40 patients with HCC who were not treated with lamivudine and matched
      for clinical features were selected. The lamivudine-treated and untreated groups
      were compared with respect to changes in liver function, HCC recurrence,
      survival, and cause of death. In the lamivudine-treated group, there was
      significant improvement in the Child-Pugh score at 24 months after starting
      treatment, while no improvement was observed in the untreated group. There was no
      significant difference in the cumulative incidence of HCC recurrence and survival
      between the groups. However, there was a significant difference in the cumulative
      incidence of death due to liver failure (P= 0.043). A significant improvement in
      liver function was achieved by lamivudine treatment, even in patients with HCC.
      These results suggest that lamivudine treatment for patients with HCC may prevent
      death due to liver failure. Further prospective randomized studies using a larger
      number of patients are required.

PMID- 16286956
TI  - Hepatic outflow obstruction created by balloon occlusion of the hepatic vein:
      induced hepatic hemodynamic changes and the therapeutic applications of hepatic
      venous occlusion with a balloon catheter in interventional radiology.
AB  - Hepatic outflow obstruction created by balloon occlusion of the hepatic vein
      induces characteristic angiographic findings in the occluded area: prolonged
      enhancement on hepatogram followed by reversed portal opacification on the
      hepatic arteriogram and perfusion defect on the arterial portogram. The following
      induced hepatic hemodynamic changes are suggested: hepatic arterial flow
      increases, and the portal vein acts as a draining vein with slow reversed flow.
      These unique hemodynamic changes enhance the effect of hepatic interventional
      therapies. In transcatheter arterial infusion, increasing hepatic arterial flow
      and absence of portal inflow can bring about a high concentration of drugs, the
      presence of which is greatly protracted due to outflow blockage. In transcatheter
      arterial chemoembolization, reversed portal flow can allow portal embolization in
      addition to arterial embolization. In microwave coagulation therapy and
      radiofrequency ablation therapy, decreasing portal flow can cause larger areas of
      coagulation. Further, the technique of hepatic venous occlusion has potential
      therapeutic applications.

PMID- 16286957
TI  - A new HLA-DRB1 genotyping method using single nucleotide polymorphism (SNP)
      analysis with multiplex primer extension reactions and its application to mixed
      samples.
AB  - We have improved on conventional methods for HLA-DRB1 genotyping and devised a
      new method that is simple, cost-effective, and adequately applicable to routine
      forensic practice. This method consists of group-specific polymerase chain
      reaction (PCR) of the exon 2 region of the HLA-DRB1 gene and simultaneous
      detection of single nucleotide polymorphisms (SNPs) at multiple sites using
      multiplex primer extension reactions. With this method, we successfully detected
      HLA-DRB1 genotypes from the following materials: the peripheral blood of 142
      donors, 6 aged saliva stains of known DRB1 genotype stored for 5-10 years at room
      temperature, 10 aged bloodstains of unknown DRB1 genotype stored for 29 years at
      room temperature, and minimal bloodstains and saliva stains from 3 donors of
      known DRB1 genotypes. Furthermore, we were able to type DRB1 alleles of the minor
      component in mixed samples at a proportion of 1/1,000 or 1/10,000. In a criminal
      case, DRB1 alleles detected from mixed bloodstains on a sword found at the scene
      enabled us to explain the case. This method is expected to be useful for forensic
      medicine.

PMID- 16286958
TI  - Long-term clinical outcomes of 420 consecutive prostate cancer patients in a
      single institute.
AB  - This study was undertaken to reveal the trends of prostate cancer and the outcome
      of treatment modalities for each disease stage in patients in a single institute
      over a 10-year period. From January 1994 through December 2003, 420 consecutive
      patients with previously untreated and histologically confirmed prostate cancer
      were analyzed for annual distributions of disease stages and treatment modalities
      and for long-term clinical progression-free survival, prostate cancer-specific
      survival, and prostate-specific antigen (PSA) failure-free survival rates for
      each stage and treatment modality. Annual trends showed that the number of
      patients, especially those with clinically localized cancer, increased
      dramatically. The 5-year disease-specific survival rates for patients with
      clinically localized disease were 100 percent for all treatment modalities,
      including hormonal therapy alone. Patients with PSA levels less than 10 ng/ml
      showed an 81 percent 5-year PSA failure-free survival rate with radical
      prostatectomy. Stage C patients treated by surgery or radiation-based therapy
      with concomitant hormonal therapy obtained 93 percent and 100 percent cause
      specific survival rates, respectively, and those treated by hormonal therapy
      alone showed a 79 percent rate. The number of patients with localized prostate
      cancer was increasing in this decade. While long-term hormonal therapy alone was
      highly efficient in controlling localized prostate cancer, radical therapies in
      conjunction with neo-adjuvant hormonal therapy produced better survival rates in
      cases of locally advanced disease.

PMID- 16286959
TI  - Resorption of apatite-wollastonite containing glass-ceramic and beta-tricalcium
      phosphate in vivo.
AB  - Apatite-wollastonite containing glass ceramic is considered to be difficult to
      resorb, but we experienced the disappearance of the porous type of Apatite
      wollastonite glass ceramic particles . In this study, the resorption of porous
      apatite-wollastonite glass-ceramic implanted in the femurs of rabbits was
      investigated, and the process was compared with beta-tricalcium phosphate, a
      resorbable ceramics. Porous apatite-wollastonite glass-ceramic (70, 80, and 90%
      porosity) and beta-tricalcium phosphate (75% porosity) were implanted in the
      femurs of Japanese white rabbits. Samples were harvested and examined 0, 4, 8,
      12, 24 and 36 weeks after implantation. Quantitative analysis of the radiographic
      and histologic findings was performed with NIH Image software. Radiographic
      examination demonstrated that the radiopacity and size of the porous apatite
      wollastonite glassceramic cylinders decreased gradually after implantation.
      Histologic examination revealed that the surface area of the apatite-wollastonite
      glass-ceramic cylinders decreased continuously, and approached 20% of the
      original area 36 weeks after implantation. However, the resorption rate of porous
      apatite-wollastonite glass-ceramic was slower than that of beta-tricalcium
      phosphate. Toluidine blue staining showed abundant new bone formation on the
      surface of the apatite-wollastonite glassceramic matrix. Considering its
      mechanical strength, gradual resorption characteristics, and good
      osteochonductive activity, porous apatite-wollastonite glass-ceramic appears to
      be a suitable artificial bone substitutes.

PMID- 16286960
TI  - The relationship between ambulation ability before surgery and the D-dimer value
      after total hip arthroplasty: the evaluation of ambulation ability by the timed
      "Up & Go" test.
AB  - We examined whether ambulatory ability before surgery might influence the post
      operative D-dimer level after total hip arthroplasty (THA). One hundred two
      patients with hip osteoarthritis receiving THA were included in the current
      study. The patients were all female, and their ages ranged from 45 to 81 (average
      65.0 +- 9.3 years). Age, operated side, body mass index (BMI), disease duration
      before surgery, pre-operative pain evaluated by visual analogue scale (VAS),
      total cholesterol value, maximal circumference of the lower leg of the operated
      side, and timed "Up & Go"test (TUG) before surgery, were retrospectively
      investigated to examine their relationship with D-dimer levels on post-operative
      day 7. Patients were divided into 2 groups according to the D-dimer value: over
      10 microg/ml (Group D), and under (Group N). Patients in group D (N= 52)were
      older, had a higher BMI, and had less ambulatory ability than patients in group N
      (N= 50). As age showed a relationship with the D-dimer value on the 7th day and
      TUG results, patients in the 2 groups were further subdivided into 50's, 60's,
      and 70's age brackets. In the 50's bracket, patients in group D had higher BMI
      than patients in group N, but time for TUG was not significantly different. In
      the 60's and 70's bracket, patients in group D had less ambulatory ability than
      patients in group N, but the time for TUG was not directly correlated with the D
      dimer value. The results suggest that pre-operative low ambulatory ability in
      patients with osteoarthritis over 60 years might influence the postoperative D
      dimer after THA, indicating the potential risk for post-operative deep venous
      thrombosis.

PMID- 16286961
TI  - Sex reassignment surgery for male to female transsexuals: initial experience in
      Okayama university hospital.
AB  - The first case of sex reassignment surgery (SRS) in our hospital was performed in
      January 2001; as of February, 2005, 4 cases of MTF-SRS had been performed. In the
      2 most recent cases, we used penile and scrotal skin flaps to avoid
      complications. The depth and width of the new vagina was made to be adequate for
      sexual intercourse. Future attention should be focused on devising a surgical
      technique that will help prevent the complications of partial necrosis of the
      epidermal skin and wound dehiscence. Although ours is only an initial experience,
      we describe our surgical technique herein.

PMID- 16286962
TI  - Term delivery choriocarcinoma patient with brain and lung metastases successfully
      treated by etoposide, methotrexate, actomycin D, cyclophosphamide and vincristine
      (EMA-CO) chemotherapy.
AB  - It is well known that antecedent term delivery and metastasis to sites other than
      the lungs and vagina are high risk factors for patients with gestational
      trophoblastic neoplasia. Here we report on a patient with choriocarcinoma who
      presented with brain and lung metastases after term delivery and was treated by
      EMA-CO chemotherapy. A 31-year-old woman delivered a healthy infant at term.
      Frequent episodes of hemoptysis occurred beginning 3 weeks after the delivery. On
      admission to our hospital, she had lesions in the uterus, lungs and brain as well
      as motor aphasia and hemiplagia. The pretreatment beta-hCG level was 21,000 ng/ml
      and the WHO score was 16 (high-risk group). The EMA-CO regimen was administrated
      as first-line chemotherapy and the patient achieved complete remission after 7
      courses. Treatment was terminated after 11 courses and maintained with etoposide
      (25 mg/day) for 6 months. The patient has remained in complete remission for more
      than 16 years without other adjuvant therapies. We believe that EMA-CO can
      currently be considered the regimen of first choice for most high-risk patients
      with gestational trophoblastic neoplasia in view of its effectiveness and
      excellent tolerability.

PMID- 16286963
TI  - Micro flow sensor based on two closely spaced amperometric sensors.
AB  - In this communication, a novel micro flow sensor based on two closely spaced
      amperometric oxygen sensors is proposed and implemented. The simulation results
      show that the ratio of the responses of these two oxygen sensors is determined by
      flow rates in the micro-channel. The sensor has been implemented using a micro
      fabrication technique. The measurement results demonstrate that the technique is
      able to detect flow rates in the flow range of several microliters per minute
      when the distance between the working electrodes of two oxygen sensors is 10
      microm and the cross-section of the micro-channel is 100 microm x 100 microm. The
      advantage of the proposed flow sensor is that no additional tracers have to be
      added or produced during the flow measurement. Information on dissolved oxygen
      concentration in the liquid is not required either.

PMID- 16286964
TI  - The autofluorescence of plastic materials and chips measured under laser
      irradiation.
AB  - Plastic materials have the potential to substitute for glass substrates used in
      microfluidic and microTAS systems adding flexibility in materials' choices.
      Optical quality plastic materials with a low autofluorescence are crucial for
      optimal detection by fluorescence and laser induced fluorescence techniques. This
      paper summarizes a series of optical investigations on commercially available
      plastic chip materials (PMMA, COC, PC, PDMS) and chips made from those materials.
      Intrinsic optical constants of plastic materials-refractive index for bulk
      materials-determined by spectroscopic ellipsometry and transmission spectroscopy
      in the visible range are presented. The laser-induced autofluorescence of
      materials and chips was assessed at four laser wavelengths, namely, 403, 488, 532
      and 633 nm. Considerable bleaching of the autofluorescence was observed under
      continuous laser illumination. Overall, the longer wavelength laser excitation
      sources yielded less autofluorescence. PDMS exhibited the least autofluorescence
      and was comparable to BoroFloat glass. In all cases, chips exhibited slightly
      higher autofluorescence than the raw plastic materials from which they had been
      made.

PMID- 16286965
TI  - Continuous flow in open microfluidics using controlled evaporation.
AB  - This paper presents a method for programming the flow rate of liquids inside open
      microfluidic networks (MFNs). A MFN comprises a number of independent flow paths,
      each of which starts with an open filling port, has a sealed microchannel in
      which assays can be performed, and an open capillary pump (CP). The MFN is placed
      over Peltier elements and its flow paths initially fill owing to capillary forces
      when liquids are added to the filling ports. A cooling Peltier element underneath
      the filling ports dynamically prevents evaporation in all filling ports using the
      ambient temperature and relative humidity as inputs. Another Peltier element
      underneath the CPs heats the pumps thereby inducing evaporation in the CPs and
      setting the flow rate in the microchannels. This method achieves flow rates in
      the microchannels ranging from approximately 1.2 nL s(-1) to approximately 30 pL
      s(-1), and is able to keep 90% of a 0.6 microL solution placed in an open filling
      port for 60 min. This simple and efficient method should be applicable to
      numerous assays or chemical reactions that require small and precise flow of
      liquids and reagents inside microfluidics.

PMID- 16286966
TI  - An integrated optical leaky waveguide sensor with electrically induced
      concentration system for the detection of bacteria.
AB  - An integrated, sensitive and rapid system was developed for the detection of
      bacteria. The system combined an optical metal-clad leaky waveguide (MCLW) sensor
      with an electric field. The electric field was used to concentrate Bacillus
      subtilis var. niger(BG) bacteria spores onto the immobilized anti-BG antibody on
      the MCLW sensor surface. This sensor combination has been characterised by
      detecting the scattering from bacterial spores, which are concentrated at the
      sensor surface, when they are illuminated at the coupling angle; and by detection
      of fluorescence from labelled antibodies added after the spores had been captured
      on the surface. The light scattering and fluorescence detection methods gave a
      detection limit of BG bacterial spores of 1 x 10(3) spores ml(-1) when the
      electric field was applied for 3 minutes.

PMID- 16286967
TI  - Electrothermal stirring for heterogeneous immunoassays.
AB  - A technique is proposed to enhance microfluidic immuno-sensors, for example,
      immunoassays, in which a ligand immobilized on a microchannel wall specifically
      binds analyte flowing through the channel. These sensors can be limited in both
      response time and sensitivity by the diffusion of analyte to the sensing surface.
      In certain applications, the sensitivity and response of these heterogeneous
      immunoassays may be improved by using AC electrokinetically-driven microscale
      fluid motion to enhance antigen motion towards immobilized ligands. Specifically,
      the electrothermal effect is used to micro-stir analyte near the binding surface.
      Numerical simulations of antigen in a microchannel flow subjected to the
      electrothermal effect show that 6 V(rms) applied to electrodes near a binding
      region can increase binding in the first few minutes by a factor of seven. The
      effectiveness of electrothermal stirring is a strong function of the Damkohler
      number. The greatest binding enhancement is possible for high Damkohler numbers,
      where the reaction is limited by diffusion. Based on these results, the utility
      of this technique for diffusion-limited microfluidic sensor applications is
      demonstrated.

PMID- 16286968
TI  - Micro gas analysis system for measurement of atmospheric hydrogen sulfide and
      sulfur dioxide.
AB  - A honeycomb structure microchannel scrubber was developed to achieve efficient
      and stable gas collection. A thin porous membrane was pasted on a microchannel by
      the adhesive force of a fresh polydimethylsiloxane surface. The microchannel
      scrubber achieved much more efficient gas collection than conventional impingers
      and diffusion scrubbers. Two sets of the microchannel scrubbers and detectors
      were integrated in a 10 cm x 9 cm plastic board to create a micro gas analysis
      system (microGAS) for simultaneous measurements of H2S and SO2. The whole system
      including a battery was incorporated in a carrying case 34 cm W x 16 cm D x 17 cm
      H for use in the field. Liquid flows at 30 microl min(-1) were obtained by
      bimetal micropumps. The estimated detection limits were 0.1 ppbv for H2S and 1
      ppbv for SO2. The system was demonstrated for real atmospheric gas analysis, and
      the results agreed well with data concurrently obtained by ion chromatography
      coupled with a cylindrical diffusion scrubber. The system we developed allowed
      automated continuous analyses in the field and achieved a much higher time
      resolution compared to those by ion chromatographic analysis.

PMID- 16286970
TI  - A novel crossed microfluidic device for the precise positioning of proteins and
      vesicles.
AB  - Herein we present a novel way to create arrays of different proteins or lipid
      vesicles using a crossed microfluidic device. The concept relies on the
      combination of I) a designated two-step surface chemistry, which allows
      activation for subsequent binding events, and II) crossing microfluidic channels
      for the local functionalization by separated laminar streams. Besides its
      simplicity and cost efficiency, this concept has the advantage that it keeps the
      proteins in a hydrated environment throughout the experiment. We have
      demonstrated the feasibility of such a device to create a chessboard pattern of
      different fluorescently labeled lipid vesicles, which offers the possibility to
      contain biomolecules, drugs or membrane proteins.

PMID- 16286969
TI  - Cell docking inside microwells within reversibly sealed microfluidic channels for
      fabricating multiphenotype cell arrays.
AB  - We present a soft lithographic method to fabricate multiphenotype cell arrays by
      capturing cells within an array of reversibly sealed microfluidic channels. The
      technique uses reversible sealing of elastomeric polydimethylsiloxane (PDMS)
      molds on surfaces to sequentially deliver various fluids or cells onto specific
      locations on a substrate. Microwells on the substrate were used to capture and
      immobilize cells within low shear stress regions inside channels. By using an
      array of channels it was possible to deposit multiple cell types, such as
      hepatocytes, fibroblasts, and embryonic stem cells, on the substrates. Upon
      formation of the cell arrays on the substrate, the PDMS mold could be removed,
      generating a multiphenotype array of cells. In addition, the orthogonal alignment
      and subsequent attachment of a secondary array of channels on the patterned
      substrates could be used to deliver fluids to the patterned cells. The ability to
      position many cell types on particular regions within a two dimensional substrate
      could potentially lead to improved high-throughput methods applicable to drug
      screening and tissue engineering.

PMID- 16286971
TI  - Construction of microfluidic chips using polydimethylsiloxane for adhesive
      bonding.
AB  - A thin layer of polydimethylsiloxane (PDMS) prepolymer, which is coated on a
      glass slide, is transferred onto the embossed area surfaces of a patterned
      substrate. This coated substrate is brought into contact with a flat plate, and
      the two structures are permanently bonded to form a sealed fluidic system by
      thermocuring (60 degrees C for 30 min) the prepolymer. The PDMS exists only at
      the contact area of the two surfaces with a negligible portion exposed to the
      microfluidic channel. This method is demonstrated by bonding microfluidic
      channels of two representative soft materials (PDMS substrate on a PDMS plate),
      and two representative hard materials (glass substrate on a glass plate). The
      effects of the adhesive layer on the electroosmotic flow (EOF) in glass channels
      are calculated and compared with the experimental results of a CE separation. For
      a channel with a size of approximately 10 to 500 microm, a approximately 200-500
      nm thick adhesive layer creates a bond without voids or excess material and has
      little effect on the EOF rate. The major advantages of this bonding method are
      its generality and its ease of use.

PMID- 16286972
TI  - On chip single-cell separation and immobilization using optical tweezers and
      thermosensitive hydrogel.
AB  - A novel approach appropriate for rapid separation and immobilization of a single
      cell by concomitantly utilizing laser manipulation and locally thermosensitive
      hydrogelation is proposed in this paper. We employed a single laser beam as
      optical tweezers for separating a target cell and locating it adjacent to a
      fabricated, transparent micro heater. Simultaneously, the target cell is
      immobilized or partially entrapped by heating the thermosensitive hydrogel with
      the micro heater. The state of the thermosensitive hydrogel can be switched from
      sol to gel and gel to sol by controlling the temperature through heating and
      cooling by the micro heater. After other unwanted cells are removed by the high
      speed cleaning flow in the microchannel, the entrapped cell is successfully
      isolated. It is possible to collect the immobilized target cell for analysis or
      culture by switching off the micro heater and releasing the cell from the
      entrapment. We demonstrated that the proposed approach is feasible for rapid
      manipulation, immobilization, cleaning, isolation and extraction of a single
      cell. The experimental results are shown here.

PMID- 16286973
TI  - A control method for steering individual particles inside liquid droplets
      actuated by electrowetting.
AB  - An algorithm is developed that allows steering of individual particles inside
      electrowetting systems by control of actuators already present in these systems.
      Particles are steered by creating time varying flow fields that carry the
      particles along their desired trajectories. Results are demonstrated using an
      experimentally validated model developed in ref. . We show that the current UCLA
      electro-wetting-on-dielectric (EWOD) system contains enough control authority to
      steer a single particle along arbitrary trajectories and to steer two particles,
      at once, along simple paths. Particle steering is limited by contact angle
      saturation and by the small number of actuators that are available to actuate the
      flow in practical electrowetting systems.

PMID- 16286974
TI  - A lab-on-a-chip compatible bioaffinity assay method for human alpha-fetoprotein.
AB  - A new lab-on-a-chip compatible binding assay platform is introduced. The platform
      combines dry-chemistry bioaffinity reagents and the recently introduced ArcDia
      TPX binding assay technique. The technique employs polymer microspheres as a
      solid phase reaction carrier, fluorescently labeled antibody conjugates, and
      detection of fluorescence emission from the surface of individual microspheres by
      two-photon excitation fluorescence. Signal response of the technique is
      independent of the reaction volume, thus the technique is particularly well
      suited for detection of bioaffinity reactions from miniature volumes. Performance
      of the new assay platform is studied by means of an immunometric assay of human
      alpha-fetoprotein (hAFP) in 384-plate format, and the results are compared to
      those of a corresponding wet-chemistry assay method. The results show that the
      ArcDia TPX detection technique can be combined with dry-chemistry reagents
      without compromises in assay performance. The microchip field has so far been
      characterized with a lack of microchip-compatible detection platforms which would
      allow cost-effective microchip design and sensitive bioaffinity detection. The
      presented detection technique is expected to provide a solution for this
      shortage.

PMID- 16286975
TI  - Bio-sensing on a chip with compact discs and nanofibers.
AB  - This paper describes a novel, sensitive detection system for biomolecules (DNA
      and proteins etc.) that is integrated in a lab-on-a-chip utilizing optical
      compact discs (CDs) and bio-nanofibers. The new method comprises a microchannel
      containing CD grating that confines fragments of unique bacterial cellulose
      fibrils (BC), which have nanometre scale fibers and holes. A maximum of six times
      higher sensitivity to detect DNA was obtained with this CD and BC system compared
      to a conventional method. We also demonstrate an effective light-confining effect
      for biological application with the new method.

PMID- 16286976
TI  - Comment on "AC frequency characteristics of coplanar impedance sensors as design
      parameters" by Jongin Hong, Dae Sung Yoon, Sung Kwan Kim, Tae Song Kim, Sanghyo
      Kim, Eugene Y. Pak and Kwangsoo No, Lab Chip, 2005, 5, 270.

PMID- 16286978
TI  - Phenotype and genotype associations of lung carcinoma with atypical adenomatoid
      hyperplasia, squamous cell dysplasia, and chromosome alterations in non
      neoplastic bronchial mucosa.
AB  - The frequency of preneoplastic lesions of the lung and bronchial mucosa as well
      as potential genotype alterations in spatial relationship to pulmonary
      malignancies still need intensive investigations in order to understand the
      occurrence and manifestation of lung cancer in detail. To investigate the
      contemporary manifestation of lung cancer precursor lesions, peripheral (non
      neoplastic) lung parenchyma and bronchial mucosa of operated lung carcinomas were
      analyzed at distinct distances (1, 2, 3, and 4 cm) from the tumor boundary for
      pre-neoplastic lesions--atypical adenomatoid hyperplasia (AAH) and squamous cell
      dysplasia (SCD), in 150 surgical specimens. Short-term tissue cultures of
      additional 55 primary and secondary lung tumors and their surrounding non
      neoplastic bronchial mucosa were performed at the same distances in order to
      search for chromosome alterations, i.e. genotype aberrations. In phenotype
      observations, atypical adenomatoid hyperplasia was noted in 19/150 (13%) cases,
      and squamous cell dysplasia in 46/150 (31%) cases. The degree of cellular atypia
      decreased with increasing distance from the tumor boundary in both AAH and SCM.
      AAH was observed more frequently in adenocarcinomas, SCQ more frequently in
      squamous cell carcinomas. In genotype observations, the average number of
      abnormal metaphases measured 4.5/10 high power fields (HPF) in primary lung
      carcinomas, and only 2/10 in metastases. Data indicate that the so-called
      preneoplastic lesions in the lung are not completely tumor-precursor lesions,
      but, in addition, induced by the tumor itself.

PMID- 16286979
TI  - Cytokeratin 20, 34betaE12 and overexpression of HER-2/neu in urine cytology as
      predictors of recurrences in superficial urothelial carcinoma.
AB  - There were investigated 80 patients with superficial urothelial carcinoma of the
      urinary bladder (Ta and T1). All cases had a minimum follow-up of 36 months.
      Patients were selected in order to form two subgroups. The first group (n = 28)
      had no recurrence during the follow-up, and in the second (n = 52) each patient
      had a minimum of two recurrences. The pathologic diagnosis was performed on
      archive slides stained with haematoxylin-eosin. Archive smears performed at the
      moment of the primary diagnosis from voided urine were discolored, and used for
      immunocytochemistry. It was investigated the expression of cytokeratin 20, high
      molecular weight cytokeratin 34betaE12, and overexpression of HER-2/neu protein.
      Microwave antigen retrieval was performed in all immunocytochemical procedures.
      The working system was LSAB2 and EnVision, and diaminobenzidine was used as
      chromogen. The initial conventional cytology was positive for malignant cells in
      all cases. Cytokeratin 20 was positive in 92.85% of cases without recurrences,
      and in 94.23% of cases with recurrences. High molecular weight cytokeratin was
      expressed in 42.85% of cases without recurrence and in 63.46% of patients with
      recurrences. The overexpression of HER-2/neu protein was found in 7.14% of cases
      of the first group, and in 84.61% of cases of the second group. Our results
      support the idea that HER-2/neu and high molecular weight cytokeratin may be used
      as markers to predict recurrence in superficial urothelial carcinoma.

PMID- 16286980
TI  - Morphologic and immunohistochemical criteria for the diagnosis of papillary
      intracystic carcinoma.
AB  - Microscopical features in papillary intracystic carcinoma are arbitrary but the
      immunohistochemical characteristics of the tumor provide important information
      for the diagnosis. SMA, factor VIII, S-100 Protein, Citokeratin together with
      Calponin can be used to assist in the interpretation of difficult papillary
      lesions.

PMID- 16286981
TI  - Preliminary study concerning the cytoscreen system importance (liquid based
      cytology) in gynecologic cytology.
AB  - Our study aims to present the principal and the advantage of using the Liquid
      Based Cytology method by Cytoscreen system, as an alternative to the conventional
      Babes-Papanicolaou test, by reducing the false negative results frequency due to
      the poor quality of the smears and the epithelial cell screening by the blood
      elements, mucus or inflammatory exudates. A set of 1 054 female patients was
      available to be investigated during 2002-2004 both in the Clinical Gynaecology of
      The Clinical Hospital Filantropia and the Clinic of Oncology of the Clinical
      County Emergency Hospital of Craiova; the patients were from the rural and urban
      places as well; they underwent cytologic screening by Cytoscreen method. We
      simultaneously performed the cytologic exam by using both the Cytoscreen and the
      conventional Papanicolaou methods in 220 patients; the rest of them, namely 834
      patients, were examined just by Cytoscreen method. The samples were processed in
      the Laboratory of Pathology and Cytology of the Clinical County Emergency
      Hospital of Craiova. The smears were fixed in the absolute ethanol for minimum
      five minutes than was performed the Papanicolaou stain. The diagnosis was
      according to Bethesda System 2001. Most of the patients (85.87%) were 21-50 aged.
      For the group of those tested by Cytoscreen, the rate of the "satisfactory
      smears" was significant increase (82.27% compared to 65.45% of the patients
      examined by using only the conventional method). The positive results were 5.44%
      compared to 2.27%. More accurate diagnosis of high degrees squamous
      intraepithelial lesions (1.36% compared to one case --0.45%), of low degree
      lesions (4 cases--1.81% compared to 2 cases--0.91%) and the atypical squamous
      cells with undetermined significance (1.36%Cytoscreen tested compared with
      0.91%). Cytologic diagnosis was enforced by biopsy with histopathologic exam for
      4 of 10 cases; the rest of the patients did not present for biopsy to be
      performed. In one case, HSIL diagnosis was false negative as the biopsy result
      was well-differentiated invasive squamous carcinoma. Both the diagnosis
      sensitivity and the smears feasibility were significantly improved by using
      Cytoscreen method.

PMID- 16286982
TI  - Salivary gland Basal cell adenomas--immunohistochemical evaluation of four cases
      and review of the literature.
AB  - OBJECTIVE: Evaluate the antigen profile of cellular population from basal cell
      adenomas. MATERIAL AND METHODS: Histopathological and immunohistochemical
      evaluation of four-salivary gland basal cell adenomas; the pathological samples
      were provided by the Oral Maxilla Facial Surgery Department of the Clinical
      County Hospital from Craiova. RESULTS: All basal cell adenoma exhibit
      differentiation toward 3 cell phenotypes: ductal luminal, basal and
      myoepithelial. CONCLUSIONS: The antigen profile of these tumors closely regard
      with other variants of salivary gland adenomas, such as pleomorphic adenoma and
      myoepithelioma. So, we can conclude that these tumors had a common origin, most
      probably from intercalated ducts and the proportion of those 3 cellular types,
      their cytoarchitectural arrangements and the quantity of extracellular matrix
      production can do the differentiation between them.

PMID- 16286983
TI  - Immunohistochemical localization of prostate-specific antigen in benign and
      malignant breast conditions.
AB  - We studied 24 selected breast tumors and 3 lymph nodes metastasis from patients
      with breast carcinoma. The biopsies were formalin-fixed, paraffin-embedded and
      sections were stained with haematoxylin-eosin. Additional sections from each case
      were immunostained for prostate specific antigen (PSA), using the EnVision
      technique. PSA was detected in 7% of normal breast tissues, in 54.5% of benign
      tumors and 46.5% of malignant tumors. The lesions with apocrine metaplasia were
      intense and constantly positive, the cystic dilated ducts and the areas with
      mastopathy were negative. Intense staining for PSA has been found in well
      differentiated tumors, while the undifferentiated tumors were usually PSA
      negative. The PSA-positivity in 2 of the 3 lymph nodes metastasis indicates that
      PSA immunoreactivity alone is not an individual prognostic indicator, but it
      correlates with the hormonal status of the female body. We discuss the results in
      terms of clinical implications of PSA immunoreactivity detection in mammary gland
      and other extra-prostatic sources.

PMID- 16286984
TI  - Cryptic fibromuscular dysplasia in the meningeal vessels. An autopsy study.
AB  - We retrospectively evaluate the presence of cryptic fibromuscular dysplasia (FMD)
      (i.e. not macroscopically visible and not associated to FMD in larger arteries)
      in the small meningeal vessels in a comprehensive series of patients. Such a
      study has not been performed before to our knowledge. The meningeal tissue has
      been systematically examined in a series of 100 consecutive autopsies. The
      immunohistochemical study was performed in one case with leptomeningeal FMD. In
      the whole series only one case had FMD in the small leptomeningeal arteries. The
      histological variant was intimal fibroplasia, a rare variant of FMD.
      Immunohistochemistry was necessary to confirm this peculiar change of the
      vascular wall. Cryptic fibromuscular dysplasia in the meninges is a very rare
      finding in our series of autopsied patients--1% of cases, in concordance with the
      literature data. The clinical associations of this lesion are difficult to be
      related to this lesion. A cryptic presence of FMD must be suspected in some cases
      with stroke.

PMID- 16286985
TI  - Histopathologic aspects of the limited endometrial hyperplasias--a study
      concerning 149 cases.
AB  - This study concerns 147 cases of limited endometrial hyperplasia, diagnosed at
      patients between IV, V, VI and VII decades of life. Histopathologically, the
      aspects were of basal hyperplasia--40 cases and polyp hyperplasia--107 cases. The
      polyp-like hyperplasia was present at pre and postmenopausal patients. At the
      premenopausal patients the polyps were hormonally active: glandular, glandular
      cystic and adenomatous type polyps. In contrast, the majority of the
      postmenopausal patients presented hormonally inactive polyps, like cystic
      atrophic or fibrous polyps. Modifying the prognosis of lesions, we took in
      consideration the morphologic changes associated with these lesions, like
      epithelial metaplasia or nuclear atypia.

PMID- 16286986
TI  - Gingival angiosarcoma: histopathologic and immunohistochemical study.
AB  - Angiosarcomas of the head and neck are rare tumors, the intra-oral localization
      being considered exceptionally in the specialty literature. The diagnosis of this
      kind of tumor in gingival location is difficult, both to the rarity of this
      lesion at this site, and to the various histopathological aspects. We present the
      case of 70 years old male patient clinically diagnosed with tumor of the alveolar
      crest of mandible, which, histopathologically, associated areas of predominant
      vascular proliferation, with areas of carcinoma and sarcoma. Immunohistochemical,
      the tumor was investigated for antibodies which prove the origin of proliferating
      cells: CD31, AE1-AE3 and vimentin.

PMID- 16286987
TI  - The construction of human body--from model to reality.
AB  - The human body building represented a complex research topic for the scientist in
      the most diverse domains. Although their interests and reasons were different,
      the goal was always the same: establishing a relation to verify the ratio between
      the dimensions of the constituent segments It appears that the mystery was solved
      out in the XIX-th century by Adolf Zeising, a German, who, using the statistic
      calculus, defined the division of a segment by the gold section. This purely
      mathematic logic confirms the human body's integration in proportion to the
      finest segments, thus providing the technical instrument of building a fully
      harmonious human body. The present study aims to compare the ideal, the
      calculated perfection to the reality, namely the theoretically obtained values to
      the average values of an 18-year-old male. It appears that the differences refer
      especially to the limbs; both the superior ones and the inferior ones being
      longer comparing to the ideal pattern while the bust is shorter and broader.

PMID- 16286988
TI  - Osteoarticular tuberculosis--a ten years case review.
AB  - Extrapulmonary sites of tuberculosis must not be neglected as they are not so
      rarely fortuitous discovering. The morphological diagnosis of tuberculosis is
      generally easy to do. However, there are the atypical lesions rising diagnostic
      difficulties. The authors reviewed the histopathological diagnostic in 19 cases
      of osteoarticular tuberculosis lesions selected from 390 cases of surgical
      extrapulmonary granulomatous lesions, using for difficult cases, with atypical
      lesions, new diagnostic tools as immunohistochemistry and DNA amplification
      technique by the polymerase chain reaction.

PMID- 16286989
TI  - Histochemical study of the skin affected by certain autoimmune diseases.
AB  - This study puts forth the morphological and metabolic modifications that occurred
      in the skin affected by Pemphigus vulgaris, modifications that have been studied
      by histoenzymatic techniques. There were studied skin biopsies from patients
      suffering from Pemphigus vulgaris, hospitalized in Dermatology services in
      Bucharest. The pieces were sectioned at cryotome, at 3 degrees C and then they
      were studied with histochemical methods, in order to evidentiate the activity of
      the following enzymes: NADH(2)-cytochrome-c-reductase, lactate-dehydrogenase
      (LDH), dihydrofolic-reductase (DHFR), folic acid (FA), ATP-ase pH 9.4, leucin
      amino-peptidase (LAP). The enzymatic activity was appreciated in all skin
      components: epidermal layers, connective tissue cells and inflammatory cells from
      the superficial and deep dermis, blood vessels, nerve fibers and encapsulated
      corpuscles. In the affected skin, there were observed modifications of all
      enzymes studied. The study revealed the following aspects: the balance between
      oxybiotic and anoxybiotic metabolism in the epidermal cells changes from the
      predominance of the former in the healthy skin, to the dominance of the latter in
      the affected skin, an active turn-over of the nucleic acids and increased
      synthesis of amino acids in the dermal cell population (mainly in the fibroblasts
      and mast cells), morphological and functional alteration of mitochondria,
      lysosomes and cellular membranes.

PMID- 16286990
TI  - Primary malignant lymphoma of the testis.
AB  - Primary testicular lymphomas are rare entities representing 1-2% of non-Hodgkin
      lymphoma (NHML) and 1-7% of malignant testicular tumors and they are the most
      common testicular tumors in men older than 50 years of age. This study included 8
      cases of inpatients diagnosed by echography and NMR with testicular tumors. The
      age of patients was between 46 and 81 (with a mean of 52). The tumors were
      unilateral, with disease limited to testicle and accompanied by pain except 1
      case with bone involvement. Orchectomy was performed as first therapeutic and
      diagnostic purpose. All patients were clinically staged according to the Ann
      Arbor criteria in IE and IIID stage and received a doxorubicin based chemotherapy
      regimen (CHOP, MTX, CVP, and Leukeran). A standard chemotherapy protocol has not
      been used because of reduced number of patients. Tumor fragments were fixed in
      10% formallin, paraffin embedded, sectioned and standard H.E. stained.
      Immunohistochemistry for L26, Alphafetoprotein, NK1, CD30, and CLA was performed.
      Microscopy revealed in all cases a stromal proliferation with medium size cells,
      monomorphic shape and prominent nucleoli. Alphafetoprotein was positive in
      seminal tubes and negative in tumor, NK1 in small lymphocyte and negative in
      tumor and L26 diffuse positive in tumor. CLA diffuse positive in tumor. We were
      able to follow up only four patients. CONCLUSIONS: The diagnosis was of NHML in 6
      cases and for 2 secondary involvement of hematopoietic malignancy (myeloid
      sarcoma and leukemia). Lymphoma cases were typed using REAL classification as
      small and large B-cell lymphoma. Unfavorable evolution with 6 months relapse and
      one death prove a more aggressive evolution of primitive testicular lymphoma.

PMID- 16286991
TI  - Cytokinin panel in rheumatoid arthritis and correlation with histological
      patterns of synovitis -- active type of disease.
AB  - Rheumatoid arthritis (RA) is a chronically inflammatory disease of the articular
      synovial, with severe, progressive and irreversible articular destruction. RA
      pathogeny implies an autoimmune mechanism, the role of cytokines resulting from
      the exaggerated production of some cytokines that act as pro-inflammatory agents,
      being directly responsible of certain symptoms and articular destructions, and/or
      inadequate inhibition of certain cytokines that act as anti-inflammatory agents.
      OBJECTIVE: We want to determine certain pro-inflammatory cytokines (tumoral-alpha
      -- TNF-alpha necrosis factor, interleukin-6 - IL-6, interleukin-8 - IL-8), anti
      inflammatory cytokines (interleukin-10 - IL-10) and immunomodulators (interleukin
      2 - IL-2) in some RA patients serum at the active stage of the disease and
      correlation with histological patterns of synovitis -- active type of disease.
      MATERIAL AND METHOD: The 37 patients have been grouped in stage I (9 patients),
      II (15 patients) and III (13 patients) according to the anatomical staging of the
      ARA (American Rheumatism Association), the serum levels of the cytokines being
      determined by ELISA technique. From the 37 patients clinical investigated only 12
      were histopathological examined. RESULTS: The serum levels of IL-2 have been
      found low in patients with RA in the active stage of the disease, the lowest
      values having been determined at the patients in the 3rd stage of the disease,
      who also have the highest values of pro-inflammatory cytokines. In the case of IL
      10 the lowest values have been found at patients in the advanced stages of the
      disease. In the serum of RA patients with follicular synovitis TNF-alpha was a
      dominant cytokine compared to patients with diffuse disease, but the greatest
      serum level was found in patient with granulomatous synovitis. Concentrations of
      IL-6 and IL-2 were highest in the serum of RA patients with follicular synovitis
      in comparison to patients with diffuse synovitis and could distinguish RA
      patients with these two histological variants of the disease. CONCLUSION: In the
      active stage of the disease the symptoms are a consequence of the interleukin pro
      and anti-inflammatory game: high serum levels of pro-inflammatory cytokines are
      accompanied by low serum levels of anti-inflammatory cytokines. Cytokines can be
      used as monitoring markers of the acutization period in RA, increase in serum
      levels of pro-inflammatory cytokines showing the progression from the inactive
      phase to a new period of activity of the disease. The association between
      distinct histological appearance of rheumatoid synovitis and serum cytokine
      profile and diverse clinical activity of disease seems to confirm its
      heterogeneity.

PMID- 16286992
TI  - Morphometric investigation of carotid body in sudden infant death syndrome.
AB  - BACKGROUND: The pathomechanism of sudden infant death syndrome (SIDS) has not
      been clarified yet. The high rate of early progenitor cells in carotid body has
      been reported as a pathognomic feature for SIDS. AIM AND STUDY DESIGN: The
      morphometric analysis was done by NIKON Eclipse microscope with a morphometric
      program Lucia G. SUBJECTS: This study was designed to investigate the structure
      and developmental state of carotid body in SIDS and non-SIDS cases. A comparison
      was made between the rates of dark and early progenitor cells. OUTCOME MEASURES:
      The Kruskal-Wallis test showed a significantly higher number of progenitor cells
      in the SIDS group than in controls (p=0.0003). RESULTS AND CONCLUSION: In this
      study on Hungarian SIDS cases we confirmed the observation that infants who died
      suddenly have an underdeveloped carotid body.

PMID- 16286993
TI  - C-erbB2 oncoprotein: prognostic marker in breast cancer.
AB  - AIM: The invasive mammary cancer is the most frequent malign tumor of a woman.
      Among the potential prognostic factors are included the biomarkers which measure
      or are associated with biological processes involved in the tumoral progression.
      We study the prognostic importance of the c-erbB2 oncoprotein in the invasive
      mammary cancer. MATERIAL AND METHODS: We included in the study 56 female patients
      suffering of invasive mammary cancer. The tissue fragments were fitted in formol,
      included to paraffin, commonly colored haematoxylin-eosine (HE); for the
      determination of the c-erbB2 we used the immunohistochemical method of avidin
      biotin (ABC) complex. RESULTS: From the total of 56 tumors, 38 (67.9%) presented
      different degrees of positivity; 18 (32.1%) did not express the oncoprotein c
      erbB2. CONCLUSIONS: The positivity of c-erbB2 oncoprotein was correlated with the
      size of the tumor; the carcinomas which are not infiltrative ductal, knows as
      having a better prognostic, were c-erbB2 negative.

PMID- 16286994
TI  - The place and the role of histological examination in diagnostic algorithm of
      urinary system tuberculosis.
AB  - The diagnosis of tuberculosis of renal and urinary tract is made by identifying
      Koch bacillus in special cultures and using histological examination of surgical
      removed pieces. Not in all cases the usual pathological techniques are very
      specific. Using special stain for acid-fast bacilli it can be certified the
      etiological diagnostic. Histological changes of renal parenchyma and/or upper
      urinary tract (renal pelvis and urether) structures in 57 patients clinical and
      paraclinical pyonephrosis diagnosed where studied. All the surgical removed
      pieces were studied using usual pathology methods. In order to find renal
      tuberculosis we performed on surgical pieces special staining (Ziehl-Nielsen), we
      noted the pathological finding in each case and we found 7 cases with certainly
      tuberculosis etiology.

PMID- 16286995
TI  - A rare case of glioblastoma multiforme.
AB  - A male, 39 years, entered rapidly in coma, was admitted in the Neurological
      Hospital Brasov and deceased after 4 hrs in hospital. At necropsy, macroscopic
      appearances of the cut surface showing unique tumour mass in all brain from
      frontal lobe to cerebellum, with extensive cortical invasion. The tumor has a
      variable coloration, a yellowish central necrosis and cysts containing turbid
      fluid. Histopathological aspect is extremely variable with regional
      heterogeneity: striking cellular pleomorphism with a lack of cell processes,
      anaplastic glial cells, and some multinucleated giant cells, large necrotic areas
      with pseudo-palisading of surrounding tumor cells and microvascular
      proliferation, as glomeruloid tufts.

PMID- 16286996
TI  - Neurofibroma, schwannoma or a hybrid tumor of the peripheral nerve sheath?
AB  - Classically, the different subtypes of the peripheral nerve sheets tumors display
      typical morphological features which differentiate them from the other nervous
      tumors. Either schwannoma or neurofibroma have characteristic histological and
      immunohistochemical features. We present a case of peripheral nerve sheets hybrid
      tumor which have had histological and immunohistochemical features of
      neurofibroma and schwannoma.

PMID- 16286997
TI  - Cell cycle regulatory factors in juxta-tumoral renal parenchyma.
AB  - The aim of this study was to evaluate regulatory cell cycle factors in juxta
      tumoral renal parenchyma in order to obtain information regarding early primary
      changes occurred in normal renal cells. Specimens of juxta-tumoral renal
      parenchyma were harvested from the tumoral kidney in 10 patients with no history
      of treatment before surgery. The expression of p53, Bcl-2, Rb and PCNA was
      studied by immunohistochemical methods in paraffin-embedded tissues. The
      apoptotic status was evaluated by flow-cytometry analysis following propidium
      iodide incorporation. The p53 protein expression was recognized in most of the
      cases (80%) with different intensities. High intensity apoptotic process detected
      in juxta-tumoral parenchyma seemed to be p53 dependent and well correlated with
      the low Bcl-2 expression. 70% of cases were Rb positive. In this type of tissue
      Rb has only an anti-proliferative and anti-tumoral role. PCNA was present in half
      of the cases being low expressed due to the tissue regenerating mechanism. Our
      data suggest that the high intensity of programmed cell death in this type of
      tissue is supported by the status of cell regulatory factors that control this
      process. Previous studies have demonstrated that healthy renal tissue has neither
      apoptosis nor mitotic activity. Juxta-tumoral renal tissue is also displaying
      normal morphology and DNA content (diploidy) but the microenvironmental status
      induced by the tumor presence prompts cells to choose death rather than malignant
      transformation. Further studies are necessary to emphasize if these results have
      a clinical relevance for the outcome of therapeutical approaches in renal
      carcinomas.

PMID- 16286998
TI  - Diagnostic significance of the immunoexpression of CD34 and smooth muscle cell
      actin in benign and malignant tumors of the breast.
AB  - PURPOSE: Our aim was to investigate the distribution of CD34 and smooth muscle
      cell actin positive myofibroblasts in the stroma of the normal mammary gland,
      benign and malignant tumors. The observations were especially focused on the
      diagnostic value of the cumulative results obtained with these immunoreactions.
      METHODS: Our study included 112 female patients with suspect breast masses
      obtained by surgery or biopsy. We performed morphological study and
      immunohistochemistry for CD34 and SMA. RESULTS: We have found normal breast
      tissue, sclerosing adenosis, fibroadenomas, fibrocystic diseases, phyllodes
      tumor, DCIS, ductal invasive, lobular, squamous, medullary, mucinous, and
      papillary carcinomas. We also found apocrine metaplasia, florid ductal
      hyperplasia, atypical hyperplasia, papilloma and LCIS associated with the
      malignant tumors. All the normal breast tissues and most of benign lesions were
      positive for CD34 and negative for SMA. The exceptions were represented by a case
      of fibroadenoma and the phyllodes tumor, with CD34 positivity and a focal
      acquisition of SMA; fibrocystic disease with associated apocrine metaplasia
      adjacent to a squamous carcinoma with loss of CD34 expression and focal
      acquisition of SMA. All our DCIS and invasive carcinomas have lost CD34
      expression and gained SMA positivity. Some particular behavior had the mucinous
      and squamous carcinomas. CONCLUSIONS: Although there were some exceptions
      especially when one of the two markers was interpreted separately and in some
      cases associated with sclerotic stroma, we conclude that the combined expression
      of CD34 and a-SMA is of potential diagnostic value in the distinction between
      benign and malignant tumors in some difficult cases.

PMID- 16286999
TI  - Morphological changes in dental pulp after the teeth preparation procedure.
AB  - The aim of this study was to evaluate the immediate changes in the pulp-dentin
      complex that result from crown preparation, and their correlation with the
      thickness of remaining dentin and the preparation technique (with or without
      water spray cooling). Thirty upper intact premolars scheduled for extraction for
      orthodontic reasons were high speed prepared, extracted immediately after
      preparation and divided in 5 groups. The analysis of the pulp morphology
      demonstrated that there are several differences according with the preparation
      technique. The most severe changes appear after the profound preparation without
      water-cooling, the odontoblastic layer being extremely affected. Also, vascular
      reactions and inflammatory infiltrate (in the absence of bacteria) were present.
      Our study revealed that the histologic changes in the pulp and dentin following
      complete crown preparation occur anyway and they are considered difficult to
      avoid, even if an adequate technique of preparation is used.

PMID- 16287001
TI  - Postmenopausal choriocarcinoma: a case report.
AB  - Postmenopausal uterine choriocarcinoma is very rare and benefits of curative
      chemotherapy. We present here the case of 62-year-old women with uterine
      bleeding. Emergency surgery revealed a uterine tumor and histopathology findings
      were consistent with choriocarcinoma. Immunohistochemistry tests confirmed
      betahCG and cytokeratin expression by malignant cells, thus establishing the
      positive diagnosis.

PMID- 16287000
TI  - Immuno-histopathological correlations in exocrine pancreatic cancer.
AB  - The CA19-9 antigen is a tumoral marker that can be found in high concentration
      within a maligned digestive pathology. OBJECTIVE: Study of CA19-9 antigen from
      the immunological point of view, at the patients with pancreatic cancer, and his
      relation with the histopathological aspects. MATERIAL AND METHOD: The
      determinations have been done at the time of the diagnosis and after the
      treatment of the patients with pancreatic cancer (25). METHOD: indirect ELISA.
      RESULTS: The values of the CA19-9 marker have been increased at the time of the
      diagnosis either in pancreatic cancer of the head and mid. At the moment of the
      diagnosis the CA19-9 marker has higher values (150-400 U/ml) in cancer of the
      pancreatic body than in cancer of the head of the pancreas (40-200 U/ml).
      Correlating the size of the tumor with the value of the CA19-9 marker in the case
      of pancreatic cancer we have been shown the highest serum values (300-400 U/ml)
      at patients whose tumor was 3 cm bigger. Four weeks post-surgery the CA19-9
      values decreased (37-100 U/ml) or reached normal levels (<37 U/ml). At patients
      with local recurrence or metastasis, especially hepatical, CA19-9 values have
      increased (100-400 U/ml in case of recurrence and 800 U/ml in case of
      metastasis). The highest values of the CA 19-9 marker were found in cases of mid
      pancreas adenocarcinoma. CONCLUSION: CA19-9 marker values higher than normal
      cause problems to digestive cancer (especially pancreatic). CA19-9 is a good
      marker for monitoring of these cancers after treatment; the favorable development
      is associated with lower values in comparison to the determinations before
      treatment, or with normal values, unfavorable evolution (local recurrence or
      metastasis) being associated with very high values. The high values of CA 19-9
      suggest an adenocarcinoma.

PMID- 16287002
TI  - Quantitative versus qualitative in the analysis of cervical squamous cell
      carcinoma.
AB  - Our work aimed to reveal and explore connections between the cellular
      morphometric features and the differentiation degree of cervical squamous cell
      carcinoma. Six cases were studied, for which biopsy was performed before the
      radiation treatment. The microscopic exam diagnosed two cases of well
      differentiated squamous cell carcinoma and four cases of moderately
      differentiated squamous cell carcinoma. The morphometric technique was developed
      in the Zeiss KS400 software environment, by implementing a script, which allowed
      measuring the cytoplasmic and nuclear areas and calculating the nucleo
      cytoplasmic ratios. For each studied case, characterized by a number of 500
      measured cells (randomly selected), the paper presents the mean, minimum and
      maximum values of the two types of areas, as well as the histograms of the nucleo
      cytoplasmic ratios. These numerical results showed that the quantitative approach
      could play an important role in enlarging the perspectives on the evaluation of
      the differentiation degree in invasive squamous cell carcinoma. Special attention
      was paid to the nucleo-cytoplasmic ratios, since we supposed they are able to
      provide enough information for quantifying several levels in the differentiation
      of the cells. Although we have obtained encouraging results, our current work
      cannot be regarded as fully confirming this assumption, because of the small
      number of cases. By involving larger groups of patients in our further
      researches, we expect to get a solid confirmation, and, thus, to support the
      refinements of the radiotherapy schemes.

PMID- 16287003
TI  - HPV and p53 expression in dysplastic lesions and squamous carcinomas of the oral
      mucosa.
AB  - We studied 18 premalignant and malignant lesions of the oral mucosa, 3
      dysplasias, and 15 oral squamous carcinomas with varied localizations: lips,
      palate, and tongue. Immunoassays for HPV were positive in 42.8% of the squamous
      carcinomas, without correlation with the pattern or the degree of differentiation
      of the lesions. P53 immuno-expression was positive in 2 of the 3 studied cases of
      dysplasia (66.6%) and in 13 from the 15 cases of squamous carcinomas (86.6%). The
      p53 immuno-positivity in both lesional categories, with a higher rate in
      carcinomas, indicates the fact that the p53 gene mutations can appear precocious
      in the oral carcinogenesis, but can not be used as malign potential prediction
      factor.

PMID- 16287004
TI  - Signet-ring prostatic carcinoma. Case presentation and review of the literature.
AB  - The authors present the case of a 71 years old man with the histopathological
      diagnosis of a signet-ring prostatic carcinoma, examined in usual and special
      stains as PAS and mucicarmin. The literature, the clinical aspect, the
      microscopic features, and the pathogenesis concerning this subject are reviewed.

PMID- 16287006
TI  - Is there life after gynaecology?

PMID- 16287007
TI  - Are oral bisphosphonates effective in improving lumbar bone mineral density in
      breast cancer survivors with osteopenia or osteoporosis?
AB  - OBJECTIVE: Breast cancer survivors with osteoporosis or osteopenia are commonly
      encountered in primary care and gynaecology practices. Our objective was to
      determine whether treatment with oral bisphosphonates (alendronate or cyclic
      etidronate) was more effective than calcium with vitamin D in improving lumbar
      spine bone mineral density (BMD) within one year in breast cancer survivors.
      METHODS: Breast cancer survivors with at least one year of clinical follow-up
      were identified from the prospective observational Canadian Database of
      Osteoporosis and Osteopenia (CANDOO). Analysis of covariance was used to examine
      the effects of bisphosphonate therapy on change in lumbar spine BMD at one year
      compared with the effects of calcium with vitamin D (analysis adjusted for
      baseline L2-L4 BMD, current tamoxifen use, number of prevalent vertebral
      fractures [VFs], and time since diagnosis of breast cancer, and age). RESULTS:
      Eighteen patients took calcium and vitamin D, 25 took cyclic etidronate, and 27
      took oral alendronate. Adjusted one-year BMD increases for alendronate and cyclic
      etidronate compared to calcium and vitamin D were as follows: alendronate 4.53%
      (95% confidence interval [CI] 1.26%, 7.81%, P = 0.008), and cyclic etidronate
      1.85% (-1.55%, 5.25%, P = 0.280). BMD increases were significantly greater in
      patients with prevalent VF compared to those without VF (P = 0.025). In contrast,
      time since diagnosis of breast cancer was significantly associated with a
      decrease in BMD (P = 0.002). We were unable to detect any effect of current
      tamoxifen use, baseline lumbar spine BMD, or age on changes in BMD at one year.
      CONCLUSION: Treatment with alendronate was associated with significantly greater
      improvements in lumbar spine BMD within one year in breast cancer survivors when
      compared with treatment with cyclic etidronate or calcium and vitamin D.

PMID- 16287009
TI  - Laparoscopic splenectomy for the treatment of refractory immune thrombocytopenia
      in pregnancy.
AB  - BACKGROUND: Immune thrombocytopenic purpura (ITP) is a condition with potential
      hazard during pregnancy for both mother and fetus if platelet concentrations fall
      below a critical level. This report describes the use of laparoscopic splenectomy
      following unsuccessful medical management. CASE: A 35-year-old primigravid woman
      with systemic lupus erythematosis (SLE) developed ITP several years before
      becoming pregnant. She was treated early in pregnancy with high-dose oral
      prednisone and weekly intravenous immunoglobulin (IVIG) alternating with anti-D
      immune globulin, but laparoscopic splenectomy was indicated at 20 weeks'
      gestation because of thrombocytopenia. Following surgery, she continued
      prednisone and intermittent IVIG therapy until spontaneous delivery at 34 weeks'
      gestation. A small accessory spleen was identified postpartum by nuclear medicine
      scan. Satisfactory platelet concentrations were maintained postpartum using
      danazol and prednisone. CONCLUSION: Laparoscopic splenectomy is a therapeutic
      option for women with ITP during pregnancy that fails to respond to medical
      management.

PMID- 16287008
TI  - Prevalence of primary dysmenorrhea in Canada.
AB  - OBJECTIVE: The aim of this study was to describe the prevalence, clinical effect,
      characteristics, and underlying risk factors of primary dysmenorrhea (PD) in
      Canada. METHODS: A stratified, random sample of 2721 women 18 years and older was
      identified, and the women were interviewed by telephone. Data about menstrual
      symptoms and patterns and socio-demographic factors were obtained. The frequency,
      severity, and effect of menstrual pain were quantified. Logistic regression
      analysis was performed in order to identify independent risk factors for PD.
      RESULTS: In the sample, 1546 women were having menstrual periods; of these, 934
      (60%) met the criteria for PD. Sixty percent of the women with PD described their
      pain as moderate or severe. Fifty-one percent reported that their activities had
      been limited, and 17% reported missing school or work because of PD. The
      prevalence of PD decreased with increasing age (P < 0.001) and increased with
      smoking (P = 0.002). Users of oral contraceptives (OCs) tended to have less pain
      than non-users (P = 0.005). Socio-economic status, nulliparity, and earlier age
      at menarche were not independently associated with PD. However, nulliparous
      women, smokers, and women not using OCs were more likely to report disabling
      symptoms. CONCLUSIONS: The majority of Canadian women will suffer from
      dysmenorrhea at some time during their reproductive years. Available prescription
      treatments are underused. Young age, smoking, and non-use of OCs are independent
      risk factors for PD.

PMID- 16287010
TI  - Improving quality of care for patients undergoing arterial embolization for
      uterine fibroids: case report and review.
AB  - BACKGROUND: Uterine artery embolization (UAE) is an effective and accepted
      management option for symptomatic uterine fibroids. This case report presents a
      complication following UAE and is followed by a review outlining the need to
      monitor quality of care for women who undergo this procedure. CASE: A 37-year-old
      woman presented with fever and general malaise refractory to medical treatment 16
      days after UAE was performed to treat a symptomatic fibroid. At hysterectomy, 20
      days after UAE, a 10 cm necrotic and infected submucosal fibroid with cervicitis
      was identified. CONCLUSION: Complications of UAE for treatment of fibroids will
      be minimized if patients are selected appropriately, if the procedure is
      performed correctly, and if outcomes, efficacy, and complication rates are
      monitored.

PMID- 16287011
TI  - Consensus guidelines for the management of chronic pelvic pain.
AB  - OBJECTIVE: To improve the understanding of chronic pelvic pain (CPP) and to
      provide evidence-based guidelines of value to primary care health professionals,
      general obstetricians and gynaecologists, and those who specialize in chronic
      pain. BURDEN OF SUFFERING: CPP is a common, debilitating condition affecting
      women. It accounts for substantial personal suffering and health care expenditure
      for interventions, including multiple consultations and medical and surgical
      therapies. Because the underlying pathophysiology of this complex condition is
      poorly understood, these treatments have met with variable success rates.
      OUTCOMES: Effectiveness of diagnostic and therapeutic options, including
      assessment of myofascial dysfunction, multidisciplinary care, a rehabilitation
      model that emphasizes achieving higher function with some pain rather than a
      cure, and appropriate use of opiates for the chronic pain state. EVIDENCE:
      Medline and the Cochrane Database from 1982 to 2004 were searched for articles in
      English on subjects related to CPP, including acute care management, myofascial
      dysfunction, and medical and surgical therapeutic options. The committee reviewed
      the literature and available data from a needs assessment of subjects with CPP,
      using a consensus approach to develop recommendations. VALUES: The quality of the
      evidence was rated using the criteria described in the Report of the Canadian
      Task Force on the Periodic Health Examination. Recommendations for practice were
      ranked according to the method described in that report (Table 1).
      RECOMMENDATIONS: The recommendations are directed to the following areas: (a) an
      understanding of the needs of women with CPP; (b) general clinical assessment;
      (c) practical assessment of pain levels; (d) myofascial pain; (e) medications and
      surgical procedures; (d) principles of opiate management; (f) increased use of
      magnetic resonance imaging (MRI); (g) documentation of the surgically observed
      extent of disease; (h) alternative therapies; (i) access to multidisciplinary
      care models that have components of physical therapy (such as exercise and
      posture) and psychology (such as cognitive-behavioural therapy), along with other
      medical disciplines, such as gynaecology and anesthesia; (j) increased attention
      to CPP in the training of health care professionals; and (k) increased attention
      to CPP in formal, high-calibre research. The committee recommends that provincial
      ministries of health pursue the creation of multidisciplinary teams to manage the
      condition.

PMID- 16287012
TI  - [Lennart Mannerfelt, August 9, 1923 to July 16, 2005].

PMID- 16287013
TI  - [Therapy for static scapholunate instability -- reconstruction of the dorsal part
      of the scapholunate ligament with a periosteal flap of the iliac crest].
AB  - Recurrent instability is frequent following capsulodesis, tenodesis, or ligament
      reconstruction in static scapholunate instability. Therefore a periosteal flap of
      the iliac crest was designed to reconstruct the dorsal part of the SL ligament,
      which is known to be the biomechanically strongest portion and also the axis of
      rotation between the scaphoid and lunate. Biomechanical testing of ten fresh
      frozen dorsal SL ligaments and ten periosteal flaps of the iliac crest showed
      similar properties concerning failure force, failure displacement, failure
      stress, energy to failure and stiffness. Results of eight specimens in each group
      were available following successful testing. Failure force of the dorsal SL
      ligament was 171.8 N (SD 44.2), energy to failure amounted 269.1 N-mm (SD 98.9),
      failure stress was 10.3 N/mm (2) (SD 1.3), failure displacement 2.9 mm (SD 0.4),
      and stiffness 77.2 N/mm (SD 21.4). Testing of the periosteal flap gave the
      following values: failure force 144.3 N (SD 38.7), energy to failure 217.9 N-mm
      (SD 85.0), failure stress 9.9 N/mm (2) (SD 1.7), failure displacement 3.0 mm (SD
      0.4) and stiffness 60.5 N/mm (SD 14.7). In addition to these test values,
      clinical and radiological data of eleven patients were available following
      reconstruction of the dorsal SL ligament with a periosteal flap of the iliac
      crest. The interval between trauma and surgery was 15 months, mean follow-up was
      29 months. One patient was free of pain, whereas ten mentioned pain during or
      following strenuous work. Two patients were completely satisfied, nine complained
      about some restriction during special activities. Active range of motion amounted
      to 56 degrees extension, 46 degrees flexion, 17 degrees radial abduction, 30
      degrees ulnar abduction. Grip strength was 38.5 kg, which was 79 % of the
      contralateral side. Radiological evaluation demonstrated a correction of the
      static instability in nine cases. In two patients recurrence of static
      instability was obvious. The prerequisite for success of the procedure is the
      easy reduction of the carpals. In cases of a fixed rotatory subluxation of the
      scaphoid, the technique cannot maintain the reduction.

PMID- 16287014
TI  - [Experiences and results with the locked compression plate for 603 fractures of
      the distal radius].
AB  - Between January 1999 and December 2003 we have treated 603 patients with a
      fracture of the distal radius without concomitant injuries with the Synthes
      locked compression plate. The locked compression plate, the concept of the
      postoperative treatment, and our results are presented. In most cases we have
      used the palmar plate. We see an indication for the palmar plate in the A2 and
      A3, B2 and B3 and in all C fractures. It is also practicable for fractures with
      dorsal comminutions. Because of its permanent retention due to the subchondral
      fixation of the splints (internal fixation), this new plate makes early
      mobilization possible. The palmar approach with its good soft-tissue coverage not
      only reduces the risk of infections but also offers the possibility of not having
      to remove the plate. A cancellous bone graft is only seldom necessary.

PMID- 16287015
TI  - [Dupuytren's contracture -- surgery of recurrencies].
AB  - BACKGROUND: The present study is a retrospective investigation of patients who
      underwent surgery for recurrence of Dupuytren's contracture. We discuss the
      indications for this intervention, operative methods, and postoperative therapy.
      Surgical treatment for recurrence of this condition is incomparably more
      difficult and risky than the primary operation. METHODS: At the Innsbruck
      University Clinic for Plastic and Reconstructive Surgery, 50 patients underwent
      70 operations for treatment of recurrence of Dupuytren's contracture between
      March 1999 and September 2004. Thorough pre- and postoperative clinical
      investigations and assessment of hand status as well as analysis of the
      indication for the first operation and the surgical method used were carried out.
      All patients underwent intensive postoperative hand therapy from day 1 for
      restoration of function and flexibility. RESULTS: After completion of therapy, in
      32 patients there was an improved ROM of between 40 and 270 degrees per finger,
      in five patients an unchanged ROM, and in three patients, reduction in ROM by 5
      to 58 degrees; six patients failed to show up for their follow-up despite being
      asked to do so several times. No data are as yet available on four patients who
      had undergone primary operation elsewhere and were operated within the past six
      months for recurrence in our clinic. In nine patients, there was a decrease in
      sensation immediately after surgery; but improvement was achieved within six
      months in three of these patients after intensive hand therapy. CONCLUSION:
      Careful assessment of hand function, establishing the indications for surgery at
      the right time, choice of the appropriate surgical approach and initiation of
      intensive hand therapy immediately after surgery are decisive for effective
      treatment of recurrent Dupuytren's contracture. However, amputations and ray
      resections cannot be avoided in all cases, especially if nerve injuries incurred
      during previous operations, resulting in joint stiffness.

PMID- 16287016
TI  - [Epidermolysis bullosa dystrophica (Hallopeau-Siemens syndrome) of the hand --
      surgical strategy and results].
AB  - Dystrophic epidermolysis bullosa is an inherited, blister-forming skin disease.
      The Hallopeau-Siemens syndrome type is one of the most severe forms. Even minimal
      trauma to the skin leads to excessive blister formation that always heals with
      scars because the defect is located in the dermis at the dermoepidermal junction.
      A genetic defect of collagen VII leads to insufficient or missing anchoring
      fibrils. The patients suffer from protein loss, anaemia, secondary infections,
      oesophageal strictures, malignant transformation and hand deformities. These
      present as pseudosyndactyly, flexion contractures and, in advanced stages, as a
      mitten-like deformity. This results in the complete loss of function of the hands
      and consequently to severe psychosocial problems for the young patients. There is
      no cure for this disease at present, so surgical treatment of the hand
      deformities is the only option. From 1998 to 2002 seven hands in four patients
      were operated on in our clinic. Operations included pseudosyndactyly separation,
      arthrolysis with Kirschner-wire fixation of finger joints, as well as
      "metacarpolysis" of the thumb. Redressing splints/dressings were applied.
      Spontaneous epithelialisation was awaited and was complete within four weeks
      without problems. Afterwards customised silicon splints and cotton gloves are
      complimented by intensive physiotherapy. There were no serious complications.
      Recurrence is unavoidable, but we could restore basic hand functions for at least
      2.5 years. Postoperative care is important to postpone reoperations. We prefer
      the most simple operative procedure as described without skin grafts, flaps or
      keratinocyte transplants, because a comparable outcome is achieved with less
      trauma and stress for the patients.

PMID- 16287017
TI  - [Indications and results of operative treatment in birth-related brachial plexus
      injuries].
AB  - INTRODUCTION: A review of the literature reveals that under conventional
      treatment alone or in combination with secondary muscle/tendon transfer about 4
      to 43 % of cases show incomplete recovery with severe functional and/or aesthetic
      impairment. When these patients undergo early microsurgical brachial plexus
      revision, a regeneration without any significant functional and/or aesthetic
      impairment can be achieved in 80 to 90 % of the cases. Moreover, microsurgical
      reconstruction of the brachial plexus does increase the possibilities of
      secondary muscle/tendon transfers. MATERIALS AND METHODS: Our concept is based on
      our experience with more than 1700 patients presenting with brachial plexus
      lesions between 1981 and 2000 who were treated in our institution. Patient
      selection is done according a standardized algorithm which is presented. There
      were 418 obstetrical brachial plexus lesions. 189 could be treated
      conservatively. In 225 cases operative treatment was necessary. 104 cases
      underwent early revision of the brachial plexus and secondary tendon transfer was
      done in 121 patients. RESULTS: Personal results and an analysis of the literature
      reveal that in C5/C6 lesions good shoulder function can be achieved in 60 to 80
      %, especially if the accessory nerve is routinely used. Good elbow function can
      be expected in over 90 %. In C5/C6/C7 lesions, there are only slightly inferior
      results. In both groups there is a significant functional improvement by
      secondary tendon transfer at the age of two to three years. In the rare C5 - Th1
      lesions, the functional results depend on the number and quality of the remaining
      roots. CONCLUSIONS: Provided there is good patient selection, severe obstetrical
      brachial plexus injuries should be scheduled for early microsurgical revision.
      There is no need to wait for a frustrating spontaneous recovery.

PMID- 16287018
TI  - Muscle transfer for shoulder reconstruction in obstetrical brachial plexus
      lesions.
AB  - A prospective study was performed on a group of 32 consecutive obstetrical
      brachial plexus lesions (OBPL). Seventeen were girls and 15 were boys with an age
      ranging between 2.3 years to 7 years (mean 3.5 years). Patients were treated
      operatively for a functionally disturbing unilateral internal rotation
      contracture of the shoulder with a good deltoid function (grade IotaIota or
      greater) and no significant active external rotation. The Hoffer technique of
      muscle transfer in the form of transferring the latissimus dorsi and teres major
      muscles to the rotator cuff posteriorly through a transaxillary approach with or
      without subscapularis muscle release was used in all cases. Preoperatively the
      patients were assessed clinically according to the modified Gilbert shoulder
      grading system. All patients were of grade 1 and 2. Eighteen patients had a
      lesion of the superior trunk of the brachial plexus (C5 and C6 roots) and ten
      patients had various degrees of involvement of the entire plexus while in four
      patients previous microsurgery reconstruction was performed. All patients
      improved to grade 4 and 5. The follow-up period ranged from 1.5 to 3.5 years
      (mean 2.3 years). There were no significant complications except for recurrence
      of minimal internal rotation in six patients that required no further surgery.
      Our results suggest that the Hoffer technique for shoulder reconstruction in OBPL
      is a reliable and safe technique.

PMID- 16287019
TI  - Microsurgical finger replantation in Hanoi, Vietnam: our first experience.
AB  - In this retrospective study, the author reports on preliminary results of finger
      replantations performed in the Department of Traumatology, Orthopaedics and Hand
      Surgery at Central Hospital 108, No. 1 Tran Hung Dao, Hanoi, Vietnam between
      September 1999 and December 2002. Forty-six amputated digits involving thirty-two
      complete and fourteen incomplete fingers were replanted and subsequently
      evaluated. The majority of the amputations was caused by avulsing or crushing
      injuries (76 %), with the left hand being predominantly affected (78.3 %). The
      overall success rate of finger replantation was 91.3 %. Secondary supplemental
      operations were performed in 8/42 (19 %) of the surviving digits, including seven
      tenolyses and one repeated osteosynthesis. The combined postoperative functional
      outcomes rated either as "good" or "fair" were 90.5 %, based on an average follow
      up period of 18 months. One surviving replant was amputated one year later due to
      lost function and paraesthesia. We concluded from the study that digit
      replantations, especially multiple amputations, are often successful and it is
      always worthwhile to attempt to restore function as well as the normal appearance
      of the hand and digits. Despite the limited postoperative movement and less than
      normal level of sensation compared to uninjured counterparts, most individuals
      with surviving replanted digits following amputations can actively and
      effectively perform normal tasks without instability or pain.

PMID- 16287020
TI  - [Ultrasound-guided blockade of axillary plexus brachialis for hand surgery].
AB  - OBJECTIVE: Blockade of the axillary plexus brachialis is an integral part of the
      anesthetic-specific procedures in the field of hand surgery. Less side-effects
      with high success rates are demanded of the surgeons and required by the
      patients. Normally, blockade of the axillary plexus brachialis is performed by
      using nerve stimulation. An alternative technique described here as a
      retrospective study uses ultrasound for detection of the nerves. METHOD: At the
      level of axilla, anatomical structures (axillary vein and artery,
      triceps/coracobrachialis muscles, ulnar/radial/median nerves) were visualized by
      ultrasound (linear scanner, 10-MHz transducer). At this position, a puncture
      needle was inserted into the nerves and local anesthetics were injected (50 ml
      prilocaine 1 % or 40 prilocaine 1 % and 20 ropivacaine 0.5 %). Parameters like
      onset time of blockade (min), complete block (yes/no) and possible complications
      were documented. RESULTS: In 30 months 221 ultrasound-guided blocks of axillary
      plexus brachialis were performed by eight anesthetists with different levels of
      training. In 96.8 % of the documented cases blockade was complete and did not
      require any supplementation. Only in seven cases was a conversion of the
      anesthetic technique performed. Adverse effects like toxic-allergic reactions or
      nerve damage caused by the punctures were not documented in any case. The average
      time to onset of the blockade was 2.2 minutes. CONCLUSION: Ultrasound-guided
      blockade of the axillary plexus brachialis represents an alternative to
      procedures using nerve stimulation, even in patients with anatomic abnormalities.
      The described method proved to be effective, especially in the field of hand
      surgery.

PMID- 16287021
TI  - [Quality of surgical continuing education in plastic surgery in Germany].
AB  - PURPOSE: Medical profession lost continuously attractiveness due to various
      reasons (insufficient training, irregular working time, decreasing income) in the
      last years. This does notably apply to surgical disciplines. In a survey should
      be clarified to what extent this dissatisfaction may be the case for residents
      and young specialists in plastic surgery. MATERIAL AND METHODS: A questionnaire
      was sent to all associated members of the "Vereinigung der Deutschen Plastischen
      Chirurgen (VDPC)" and was published in the communication journal of the VDPC. The
      questionnaire was sent back by 91 surgical residents or newly specialists (about
      19 % of all). RESULTS: A well structured residency program existed for 47 %. 40 %
      of the residents were satisfied with the teaching assistance by their clinical
      teachers in the OR, whereas the fewest surgical procedures were done in the field
      of aesthetic surgery (n = 7). At least once per year it was possible for 80 % to
      take part in seminars or congresses. Therefore 45 % had to take holyday. For 44 %
      no financial support was paid. As perspective 30 % aim a career advancement in
      their hospitals and 18 % aim a private practice as plastic surgeon. CONCLUSION:
      To some extent training structures in plastic surgery are not well established.
      An urgent challenge should be to develop improvements in the continuing education
      in plastic surgery. This includes an increase in internal training, an organised
      rotation of residents between different hospitals, and structured mentoring of
      the residents.

PMID- 16287022
TI  - [Continuing education in anesthesiology in the age of internet -- are we still up
      to date?].

PMID- 16287023
TI  - [Topographic electroencephalography: endotracheal intubation during anaesthesia
      with propofol/fentanyl].
AB  - OBJECTIVE: We used quantitative analysis of the electroencephalogram (EEG) during
      routine clinical practice to assess the effect of tracheal intubation following
      induction of anesthesia with propofol and fentanyl. METHODS: The topographic EEG
      was recorded from eight bipolar electrode derivations in 25 patients. Z-scores
      relative to age expected normative data were computed for relative power in the
      delta, theta, alpha and beta frequency bands. Multivariate statistics
      (Hotellings' t-sqare) were used to evaluate changes in regional brain electrical
      activity. RESULTS: Tracheal intubation induced an increase in alpha and beta
      frequencies, while delta power was reduced (F-values: Delta: 7.68, p = 0.011;
      Alpha 31.93; p < 0.001; Beta 12.85, p = 0.001). The most pronounced regional
      effect was seen for the alpha frequency band with the largest increase in both
      fronto-temporal regions (F-value 33.89, p < 0.001). During clinical practice the
      patients received propofol 2.7 (+/- 1.2; minimum: 0.5, maximum 6.9) mg kg (- 1)
      and fentanyl 2 (+/- 1; minimum 1, maximum 4) microg kg (- 1). Vital parameters
      did not change during intubation. CONCLUSION: Individual titration of the dose of
      propofol and fentanyl as done during routine clinical practice is not sufficient
      to block the strong noxious stimulation of intubation. Tracheal intubation
      resulted in "classical" cortical arousal. It remains open whether this cortical
      wake-up phenomenon has a clinical impact.

PMID- 16287024
TI  - [Systemic optimisation of oxygen-delivery -- cardiac improvement].

PMID- 16287025
TI  - [Surgical treatment of cardiac failure].

PMID- 16287026
TI  - [Adequacy of hepatosplanchnical oxygen supply].

PMID- 16287027
TI  - [Increase of oxygen supply for the fetus -- a challenge for the obstetrician and
      the anesthetist].

PMID- 16287028
TI  - [Respiratory emergencies in children].

PMID- 16287031
TI  - An integrated strategy for identification and relative quantification of site
      specific protein phosphorylation using liquid chromatography coupled to MS2/MS3.
AB  - Reversible and differential multisite protein phosphorylation is an important
      mechanism controlling the activity of cellular proteins. Here we describe a
      robust and highly selective approach for the identification and relative
      quantification of site-specific phosphorylation events. This integrated strategy
      has three major parts: visualisation of phosphorylated proteins using
      fluorescently stained polyacrylamide gels, determination of the phosphorylation
      site(s) using automatic MS3 triggered by the loss of phosphoric acid, and
      relative quantification of phosphorylation by integrating MS2- and MS3-extracted
      ion traces using a fast-scanning, linear ion trap mass spectrometer. As a test
      case, recombinant sucrose-phosphate synthase (SPS) from Arabidopsis thaliana
      (At5g1110) was used for identification and quantification of site-specific
      phosphorylation. The identified phosphorylation site of the actively expressed
      protein coincides with the major regulatory in vivo phosphorylation site in
      spinach SPS. Site-specific differential in vitro phosphorylation of native
      protein was demonstrated after incubation of the recombinant protein with cold
      adapted plant leaf extracts from A. thaliana, suggesting regulatory
      phosphorylation events of this key enzyme under stress response.

PMID- 16287030
TI  - Tandem mass spectrometry for the characterisation of sulphated-phosphorylated
      analogues of the carbohydrate-protein linkage region of proteoglycans.
AB  - Carbohydrate-protein linkage region of proteoglycans is a key oligosaccharide
      structure because their sulphated and/or phosphorylated analogues control the
      biosynthesis of glucosaminoglycans or galactosaminoglycans. Therefore,
      synthesised sulphated and/or phosphorylated analogues were characterised by
      tandem mass spectrometry in the negative-ion mode. Results demonstrated that the
      product ion profile was characterised by glycosidic and cross-ring cleavages
      depending on the position and the type of the charged group (sulphate, phosphate
      or carboxylate). When the above compounds were sulphated and phosphorylated, the
      ion found at m/z 79 was the only one that demonstrated a phosphate group on the
      structure. The data also suggested that when a sodium cation was present in a
      sulphated and phosphorylated structure, the phosphate group in most cases was
      neutralised by the sodium cation, and therefore cleaved off the molecule, while
      the sulphate group was carrying the negative charge.

PMID- 16287032
TI  - Characterization of industrial alkylpolyphosphonates by infusion electrospray
      ionization-ion trap mass spectrometry with identification of the impurities by
      tandem capillary zone electrophoresis.
AB  - Technical grade diethylene-triaminepentakis(methylenephosphonic acid) (I),
      dihexamethylene-triaminepentakis(methylenephosphonic acid) (II), ethylene
      diaminetetrakis(methylenephosphonic acid) (III), hexamethylene
      diaminetetrakis(methylenephosphonic acid) (IV), amino-tris(methylenephosphonic
      acid) (V), hydroxyethyl-aminobis(methylenephosphonic acid) (VI), 1
      hydroxyethylidene-1,1-diphosphonic acid (VII), and 2-phosphonobutane-1,2,4
      tricarboxylic acid (VIII) were characterized by ion trap mass spectrometry with
      electrospray ionization (ESI-ITMS). Using the negative ion mode and acid and
      alkaline media, peak series corresponding to the nominal compounds and to
      impurities with a lower number of phosphonate groups were distinguished in I-V.
      Each series was constituted by [M - nH + (n - 1)Na](-) peaks and peaks produced
      from them by losses of water, H(3)PO(3)(or water plus HPO(2)), and combined
      losses. For each [M - nH + (n - 1)Na](-) peak, the number of losses coincided
      with the number of phosphonate groups not bound to sodium ions minus one (the
      group bearing the charge). Owing to the hydroxyethyl group, the spectrum of VI
      was dominated by the formation of intermolecular esters, with both losses and
      gains of water according to [nM - H +/- mH(2)O](-). A series of [M - nH + (n -
      1)Na](-) peaks were observed for VII and VIII, showing in the latter case that
      the carboxylate groups may also form adducts with sodium ions. Losses of water
      and H(3)PO(3)were observed in VII, whereas losses of water, CO(2), and HPO(3)
      were seen in VIII. The reaction pathways leading to the production of the
      observed ions are described. The nominal compounds and the impurities were also
      separated and identified by capillary electrophoresis with ESI-ITMS detection.

PMID- 16287033
TI  - Isotope dilution SPME GC/MS for the determination of methylmercury in tuna fish
      samples.
AB  - The development of a rapid, precise and accurate analytical method for the
      determination of methylmercury in tuna fish samples is described. The method is
      based on the use of isotope dilution GC/MS with electron impact ionization, a
      widespread technique in routine testing laboratories. A certified spike
      containing (202)Hg-enriched methylmercury was used for the isotope dilution of
      the samples. After extraction of the methylmercury from the sample, methylmercury
      was propylated using sodium tetrapropyl borate in SPME vials and the analytes
      were sampled from the headspace for 15 min. For isotope measurements, the
      molecular ion (MePrHg(+)) was used in the SIM mode. Five molecular ions were
      monitored, corresponding to the (198)Hg, (199)Hg, (200)Hg, (201)Hg and (202)Hg
      isotopes. The detection at masses corresponding to (198)Hg was used to correct
      for m + 1 contributions of (13)C from the organic groups attached to the mercury
      atom on the (199)Hg, (200)Hg, (201)Hg and (202)Hg masses with simple mathematical
      equations, and the concentration of methylmercury was calculated on the basis of
      the corrected (200)Hg/(202)Hg isotope ratio. The (202)Hg-enriched methylmercury
      spike was applied, with satisfactory results, to the determination of
      methylmercury in the certified reference material BCR 464. The method was
      successfully applied to the determination of methylmercury in tuna fish samples,
      and the obtained results were included in the CCQM-P39 interlaboratory exercise,
      organized by the Institute for Reference Materials and Measurements (IRMM, Geel,
      Belgium) with excellent agreement between our results and the average obtained by
      the other participants.

PMID- 16287034
TI  - Atmospheric pressure photoionization coupled to porous graphitic carbon liquid
      chromatography for the analysis of globotriaosylceramides. Application to Fabry
      disease.
AB  - Globotriaosylceramides (Gb(3)) are biological compounds implicated in Fabry
      disease, a lysosomal storage disease due to the deficient activity of alpha-D
      galactosidase A, which results in an accumulation of Gb(3) in many organs. The
      naturally occurring samples are composed of mixtures of several molecular species
      differing by the structure of the alkyl chains and the nature of the sphingoid
      base. Atmospheric pressure photoionization mass spectrometry (APPI-MS) proved to
      be an efficient method for the analysis of globotriaosylceramide molecular
      species, both in direct injection and by coupling with liquid chromatography
      (LC). In the positive ion mode, in-source fragmentations yield very precious
      information that can be used to determine the structure of the alkyl chains. In
      the negative ion mode, the chloroform solvent participates to the analyte
      ionization by forming an adduct with chloride ions generated in situ. Combination
      of LC on a Porous Graphitic Carbon stationary phase and APPI-MS allowed the
      detection of a great number of species from biological samples isolated from
      Fabry patients. This method could be an interesting analytical tool for the
      biochemical investigation of (sphingo) lipid metabolism.

PMID- 16287036
TI  - Determination of lafutidine in human plasma by high-performance liquid
      chromatography-electrospray ionization mass spectrometry: application to a
      bioequivalence study.
AB  - A rapid, sensitive and specific high-performance liquid chromatography
      electrospray ionization mass spectrometry (LC/ESI-MS) method was developed and
      validated for the first time to determine the concentration of lafutidine in
      human plasma. After the addition of diazepam (the internal standard, IS) and 1 M
      sodium hydroxide solution to 0.5-ml plasma sample, lafutidine was extracted from
      plasma with n-hexane : isopropanol (95 : 5, v/v). The organic layer was
      evaporated and the residue was redissolved in 200-microl mobile phase. The
      analyte was chromatographically separated on a prepacked Shimadzu Shim-pack VP
      ODS C(18) column (250 x 2.0 mm i.d.) using a mixture of methanol-water (20 mM
      CH(3)COONH(4)) = 80 : 20 (v/v) as mobile phase. Detection was performed on a
      single quadrupole mass spectrometer using an electrospray ionization interface
      and the selected-ion monitoring (SIM) mode. The method showed excellent linearity
      (r = 0.9993) over the concentration range of 5-400 ng/ml and had good accuracy
      and precision. The within- and between-batch precisions were within 10% relative
      standard deviation. The limit of detection was 1 ng/ml. The validated LC/ESI-MS
      method has been successfully applied to the bioequivalence study of lafutidine in
      24 healthy male Chinese volunteers.

PMID- 16287035
TI  - Rapid accurate mass desorption electrospray ionisation tandem mass spectrometry
      of pharmaceutical samples.
AB  - Desorption electrospray ionisation (DESI) has been successfully combined with a
      hybrid quadrupole time-of-flight mass spectrometer to provide mass spectra and
      product ion mass spectra of active ingredients formulated in pharmaceutical
      tablets, gels and ointments. Accurate mass data has been obtained from the DESI
      mass spectra and of the product ion fragments of selected ions, greatly enhancing
      the selectivity and information content of the experiment. This accurate mass
      information only takes seconds to acquire since the DESI technique does not
      require any sample preparation or extraction prior to mass analysis.

PMID- 16287037
TI  - Mass spectral studies of a series of N,N-dialkyl aminoethyl-2-chlorides and
      trimethyl silyl ethers of N,N-dialkyl aminoethane-2-ols under electron impact
      conditions.
AB  - The electron impact (EI) mass spectra of a series of N,N-dialkyl-aminoethyl-2
      chlorides, N(R(1))(R(2))-CH(2)-CH(2)Cl and trimethylsilyl ethers of N,N-dialkyl
      aminoethane-2-ols, N(R(1))(R(2))-CH(2)-CH(2)-O-Si(CH(3))(3), where R(1) and R(2)
      = methyl, ethyl, propyl and isopropyl, which are precursors of VX type of
      compounds, are studied. All the compounds (1-20) show abundant molecular ions, in
      addition to a weak [M - H](+) ion, except the N,N-diisopropyl group containing
      compounds (8 and 18). A general EI fragmentation pattern for the above two series
      of compounds is discussed. The observed fragment ions are due to simple homolytic
      cleavages, and they are distinct to allow the identification of the compounds
      unequivocally including those of isomeric compounds. The primary fragmentation of
      compounds 1-20 is beta-cleavage, i.e. homolytic cleavage of C-C bond, which is
      linked to the nitrogen atom. Three types of beta-cleavages are possible for these
      compounds, in which the abundance of beta-cleavage product ions is found to
      depend on the size and structure of the alkyl group attached to nitrogen. The
      alpha-cleavage fragment ions are found only for N,N-dialkyl aminoethyl-2
      chlorides but are absent in the corresponding trimethylsilyl ethers of N,N
      dialkyl aminoethane-2-ols. The retention indices are calculated for all the
      studied compounds (1-20) and are in the ranges of 750.38-1079.24 for 1-10 and
      905.23-1190.25 for 11-20.

PMID- 16287040
TI  - Analysis of proteins from a glioma cell line by using micro-scale solution
      isoelectric focusing in combination with liquid chromatography/tandem mass
      spectrometry.
AB  - In this study we have investigated whether micro-solution isoelectric focusing
      (microsol-IEF) can be used as a pre-fractionation step prior to liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) and if extensive sample
      purification of the different fractions is required. We found that, in spite of
      the high concentrations of buffer and detergents, no clean up of the digested
      microsol-IEF fractions was necessary before analysis by LC/MS/MS. We also
      concluded that it is possible to identify at least twice as many proteins in a
      glioma cell lysate with the combination of microsol-IEF and LC/MS/MS than with
      LC/MS/MS alone. Furthermore, most of the proteins that were identified from one
      microsol-IEF fraction by using analytical narrow-range two-dimensional
      polyacrylamide gel electrophoresis (2D-PAGE) and peptide mass fingerprinting with
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOFMS) were also identified by LC/MS/MS. Finally, we used the combination
      of microsol-IEF and LC/MS/MS to compare two sample preparation methods for glioma
      cells and found that several nuclear, mitochondria, and endoplasmic reticulum
      proteins were only present in the sample that had been subjected to lipid
      extraction by incubating the homogenized cells in chloroform/methanol/water.

PMID- 16287039
TI  - Simultaneous quantification of fludarabine and cyclophosphamide in human plasma
      by high-performance liquid chromatography coupled with electrospray ionization
      tandem mass spectrometry.
AB  - Fludarabine and cyclophosphamide are anticancer agents mainly used in the
      treatment of hematologic malignancies. We have developed and validated an assay
      using high-performance liquid chromatography (HPLC) coupled with electrospray
      ionization tandem mass spectrometry for the quantification of fludarabine in
      combination with cyclophosphamide in human heparin and human EDTA plasma. Sample
      pre-treatment consisted of a protein precipitation with cold acetonitrile (-20
      degrees C) using 250 microL of plasma. Separation was performed on an Extend C18
      column (150 x 2.1 mm i.d.; 5 microm) with a stepwise gradient using 1 mM ammonia
      solution and acetonitrile at a flow rate of 400 microL/min. The analytical run
      time was 12 min. The triple quadrupole mass spectrometer was operated in the
      positive ion mode and multiple reaction monitoring was used for drug
      quantification. The method was validated over a concentration range of 1 to 100
      ng/mL for fludarabine and cyclophosphamide in human heparin and human EDTA
      plasma. The coefficients of variation were <13.9% for inter- and intra-day
      precisions. Mean accuracies were also within the designated limits (+/-15%). The
      analytes were stable in plasma, processed extracts and in stock solution under
      all relevant conditions.

PMID- 16287041
TI  - Characterisation and proposed origin of mass spectrometric ions observed 30 Th
      above the ionised molecules of per-O-methylated carbohydrates.
AB  - Derivatisation of carbohydrates by permethylation significantly improves the mass
      spectrometric intensity of carbohydrate-derived ions and allows more readily
      interpretable fragmentation; in addition, samples are conveniently separated from
      salts, and larger oligosaccharides are more readily ionised. It has previously
      been recognised that, in the mass spectra of permethylated carbohydrates, a
      series of ions indicating species 30 Da larger than the fully methylated
      carbohydrate molecules are also observed. These species have not been
      characterised in the literature despite their apparently ubiquitous occurrence in
      the mass spectra of permethylated carbohydrates. Tandem mass spectrometry (MS/MS)
      experiments were performed on permethylated carbohydrates and reduced
      permethylated carbohydrates that exhibit the artefact, demonstrating that the
      artefact is not reducing terminal specific, and that the artefact can be
      introduced at any hydroxyl residue. It was further demonstrated through the use
      of different alkylation reagents that the origin of this artefact group is the
      alkylating reagent itself. It is proposed that side reactions that occur between
      the permethylation reagents allow the production of small amounts of iodomethyl
      methyl ether. This reagent can then compete with methyl iodide for reaction with
      the carbohydrate -OH groups. The result is partial incorporation of a
      methoxymethyl moiety instead of a methyl group, detected as '+30' artefact ions.

PMID- 16287042
TI  - Determination of ethyl glucuronide in hair samples by liquid
      chromatography/electrospray tandem mass spectrometry.
AB  - A method for the determination of ethyl glucuronide (EtG) in hair samples, using
      liquid chromatography/electrospray tandem mass spectrometry (LC/ESI-MS/MS), was
      developed and validated. The treatment of hair samples was as follows: to 100 mg
      of washed (dichloromethane followed by methanol, 1 ml each) and cut (1-2 mm)
      material, 700 microl of water, 20 microl of internal standard solution
      (pentadeuterated EtG, D(5)-EtG, 500 microg/l) and 20 microl of methanol were
      added. Samples were incubated at 25 degrees C overnight and then ultrasonicated
      for 2 h. Finally, 8 microl of the centrifuged solution (13,000 rpm) were analyzed
      by LC/ESI-MS/MS in negative ion mode. The surviving ions of EtG and D(5)-EtG were
      monitored together with the following MRM transitions: m/z 221 --> 75, m/z 221 -
      > 85 (EtG) and m/z 226 --> 75, m/z 226 --> 85 (D(5)-EtG). The method exhibited a
      mean correlation coefficient better than 0.9998 over the dynamic range (3-2000
      pg/mg). The lower limit of quantification (LLOQ) and the limit of detection (LOD)
      were 3 and 2 pg/mg respectively. The intra- and interday precision and accuracy
      were studied at four different concentration levels (3, 5, 56 and 160 pg/mg) and
      were always better than 7% (n = 5). Matrix effects did not exceed 20%. The method
      was applied to several hair samples taken from autopsies of known alcoholics,
      from patients in withdrawal treatment, from social drinkers, from adult
      teetotalers and from children not exposed to ethanol, with EtG concentrations
      globally ranging from < or =2 to 4180 pg/mg.

PMID- 16287043
TI  - A preliminary comparison of the hopes of researchers, clinicians, and families
      for the future ethical use of genetic findings on schizophrenia.
AB  - A written questionnaire about genetic testing was distributed to all registrants
      at The 2004 World Congress of Psychiatric Genetics, mailed to clinical
      psychiatrists obtained from a directory of clinicians practicing in New York
      City, and mailed to members of families who have multiple affected family members
      with schizophrenia. A total of 274 individuals responded (162 researchers, 64
      clinicians, and 48 family members). This survey shows that the majority of family
      members who completed the questionnaire (83.3%) would want to be tested if a
      genetic test were to become available. Over half of the family members (56.2%)
      would want prenatal testing. Similarly, over half of the clinicians (56.3%) would
      recommend it, despite only 25% of the researchers reporting that it would be a
      future useful tool. All of the clinicians surveyed thought adoption agencies
      should inform families about a family history of schizophrenia, while only half
      of the researchers thought this should be done (51.9%). These differences in
      opinions between consumers, their clinicians, and researchers could be based on a
      lack of understanding of the amount of risk conferred to family members by
      reported gene variants. Providing public discussions for placing these risks in
      perspective should be the responsibility of researchers. Open public discussion
      of the ethical and social uses of the information gained from psychiatric genetic
      research and its limitations is encouraged.

PMID- 16287044
TI  - Genetic etiology of stability of attention problems in young adulthood.
AB  - Variation in attention problems in children and adolescents from non-clinical
      samples is highly heritable. It is unknown how attention problems develop later
      in life and whether the heritability in the general adult population is the same
      as in children and adolescents. We assessed the heritability and stability of
      individual differences in attention problems in the general young adult
      population and explored to what extent the stability can be attributed to genetic
      or environmental factors. On one or more occasions, young adult twins (age range,
      18-30 years, N = 4,245) from the Netherlands Twin Registry filled out the
      attention problems (AP) subscale of the Young Adult Self-Report [Achenbach,
      1997]: in 1991, N = 1,755 (of which 842 complete pairs), in 1995, N = 2,428 (1156
      complete pairs) and in 1997, N = 2,344 (958 pairs). There was only a slight
      decrease in the average level of attention problems during young adulthood. The
      heritability at each occasion was around 40%. The correlation of attention
      problems across a period of 6 years was 0.42, and 77% of this correlation could
      be ascribed to genetic influences. Thus, individual differences in attention
      problems in young adulthood are heritable, and stability in individual
      differences over time can largely be ascribed to genetic influences. Genetic
      correlations across time were high, suggesting that the genes that influence
      variability in attention problems in late adolescence are largely the same as
      those that influence variability in early adulthood.

PMID- 16287045
TI  - Prion genotypes in Central America suggest selection for the V129 allele.
AB  - Using the well-characterized, human diversity sample series, we show that the
      V129 prion allele has a very high frequency in South American populations
      relative to the East Asian populations from which it arose. We suggest there has
      been selection at the prion locus, possibly mediated by Kuru-like diseases, which
      has influenced its allele frequency.

PMID- 16287046
TI  - Analysis of polymorphisms in AT-rich domains of neuregulin 1 gene in
      schizophrenia.
AB  - Linkage analysis and association studies have pointed to neuregulin 1 (NRG1) as
      the prime candidate for 8p-linked schizophrenia (SZ). However, so far, no
      specific functional alleles in the gene's exons, intron-exon junctions and
      promoters have been identified that are unequivocally associated with SZ. In this
      study, we analyzed several NRG1 polymorphisms that affect ATTT motifs and AT-rich
      regions of the gene. We have previously identified a number of such polymorphisms
      in the promoters of other SZ and bipolar disorder (BD) candidate genes and found
      positive associations to several of them. In addition, allele specific
      differences in the binding of brain proteins have been found for many of the
      polymorphisms. A case control design was used to compare allele frequencies in
      Caucasian and African American patients with SZ and controls. In the African
      American group, a significant difference was found in the allele and genotype
      distribution for several of the markers and haplotype blocks located in the 5'-
      and 3'-ends of the gene. The most significant result was obtained for rs6150532,
      an insertion/deletion variant in a conserved region of an intron that separates
      two small, alternatively spliced exons. Allele-specific and developmental
      differences were detected in the binding of a brain protein using newborn rat
      pups when probes containing the two rs6150532 alleles were used in
      electromobility gel shift assays. There were no significant differences in allele
      or genotype distribution found for any of the markers in the Caucasian sample.
      Although the samples size is relatively small, the findings support a role for
      NRG1 in SZ in African Americans and suggest that polymorphic differences in
      regions of the gene that recognize AT-binding proteins may be a factor in disease
      pathogenesis.

PMID- 16287047
TI  - Determination of the stereoselectivity of chiral drug transport across Caco-2
      cell monolayers.
AB  - This study aimed to determine the transport characteristics of chiral drug
      enantiomers across Caco-2 cell monolayers as a model of human intestinal
      epithelial membrane. Esmolol was chosen as a model drug, and the study focused on
      the transepithelial transport of esmolol enantiomers in this in vitro model
      system. Separation and quantitation of (S)- and (R)-esmolol were performed by RP
      HPLC with the use of GITC as a precolumn derivatizing agent. Bidirectional
      transport studies of 5.0-400.0 micromol/l esmolol demonstrated that the two
      enantiomers were transported mainly by a passive, transcellular mechanism. At
      concentrations of 5.0-100.0 micromol/l, enantioselective permeability of esmolol
      was observed. In the absorptive transport, Papp of (S)-esmolol was smaller than
      (R)-esmolol and vice versa for secretory transport. The enantioselectivity
      disappeared when the drug concentration was increased to 200.0 micromol/l. In
      conclusion, the transport characteristics of (S)- and (R)-esmolol were distinctly
      different. An enantioselective carrier-mediated mechanism in addition to passive
      diffusion was involved in the transport process of esmolol across Caco-2 cell
      monolayers.

PMID- 16287051
TI  - Effects of music therapy on women's physiologic measures, anxiety, and
      satisfaction during cesarean delivery.
AB  - The purpose of the study was to investigate the effects of music therapy on
      women's physiologic measures, level of anxiety, and satisfaction during cesarean
      delivery. Sixty-four women who were planning to have a cesarean delivery were
      randomly divided into an experimental and a control group. The experimental group
      received routine care and music therapy, whereas the control group received
      routine care only. Our results indicated that compared to the control group the
      experimental group had significantly lower anxiety and a higher level of
      satisfaction regarding the cesarean experience. No significant differences were
      found between the two groups in any of the physiological indexes. This controlled
      study provides evidence that music therapy can reduce anxiety and create a more
      satisfying experience for women undergoing cesarean delivery.

PMID- 16287050
TI  - Optimized green fluorescent protein variants provide improved single cell
      resolution of transgene expression in ascidian embryos.
AB  - The green fluorescent protein (GFP) is used extensively to monitor gene
      expression and protein localization in living cells, particularly in developing
      embryos from a variety of species. Several GFP mutations have been characterized
      that improve protein expression and alter the emission spectra to produce
      proteins that emit green, blue, cyan, and yellow wavelengths. DsRed and its
      variants encode proteins that emit in the orange to red wavelengths. Many of
      these commercially available fluorescent proteins have been "codon optimized" for
      maximal levels of expression in mammalian cells. We have generated several
      fluorescent protein color variants that have been codon optimized for maximal
      expression in the ascidian Ciona intestinalis. By analyzing quantitative time
      lapse recordings of transgenic embryos, we demonstrate that, in general, our
      Ciona optimized variants are detected and expressed at higher levels than
      commercially available fluorescent proteins. We show that three of these
      proteins, expressed simultaneously in different spatial domains within the same
      transgenic embryo are easily detectable using optimized fluorescent filter sets
      for epifluorescent microscopy. Coupled with recently developed quantitative
      imaging techniques, our GFP variants should provide useful reagents for
      monitoring the simultaneous expression of multiple genes in transgenic ascidian
      embryos.

PMID- 16287054
TI  - Top 10 tips for successful qualitative grantsmanship.

PMID- 16287052
TI  - Handling missing data in self-report measures.
AB  - Self-report measures are extensively used in nursing research. Data derived from
      such reports can be compromised by the problem of missing data. To help ensure
      accurate parameter estimates and valid research results, the problem of missing
      data needs to be appropriately addressed. However, a review of nursing research
      literature revealed that issues such as the extent and pattern of missingness,
      and the approach used to handle missing data are seldom reported. The purpose of
      this article is to provide researchers with a conceptual overview of the issues
      associated with missing data, procedures used in determining the pattern of
      missingness, and techniques for handling missing data. The article also
      highlights the advantages and disadvantages of these techniques, and makes
      distinctions between data that are missing at the item versus variable levels.
      Missing data handling techniques addressed in this article include deletion
      approaches, mean substitution, regression-based imputation, hot-deck imputation,
      multiple imputation, and maximum likelihood imputation.

PMID- 16287055
TI  - Sleep, memory, and learning in off-pump coronary artery bypass patients.
AB  - In this study, I examined sleep, memory, and learning in off-pump coronary artery
      bypass (OPCAB) patients. Sixty-six men and women aged >or=60 years wore
      actigraphs to record sleep and completed sleep diaries for two 24-hour periods
      following OPCAB surgery. Prior to discharge from the hospital, participants
      completed the Pittsburgh Sleep Quality Index (PSQI) and Rey Auditory Verbal
      Learning Test. No significant correlations were found between habitual sleep,
      sleep time, efficiency, number, and duration of awakenings, daytime napping, or
      memory and learning. Nighttime sleep was short with frequent disturbances, and
      daytime sleep accounted for half the daily sleep time. Participants scored low in
      learning and delayed recall. These findings suggest the need to assess sleep and
      cognition in patients recovering from OPCAB surgery.

PMID- 16287057
TI  - Why carve up your continuous data?
AB  - Continuous data are commonplace in social, biophysical, and health research. For
      various reasons, researchers often carve up data into ordered chunks. Such data
      carving results in less information being carried by the data, a reduction or
      spurious increase in statistical power, and resultant Type I or Type II errors.
      We give examples of data carving in selected nursing literature, and illustrate
      how unnecessary categorization can produce erroneous statistical results.
      Finally, we propose credible alternatives to data carving.

PMID- 16287056
TI  - Psychometric properties of a Chinese version of the critical care family needs
      inventory.
AB  - The Critical Care Family Needs Inventory (CCFNI) was developed to measure family
      needs of patients with critical illness. However, testing of the CCFNI has not
      been undertaken for a Chinese-speaking population. The purpose of this study was
      to assess the psychometric properties of a Chinese version of the CCFNI in a
      sample of Chinese family members of critically ill patients. Translation into
      Chinese and reverse translation were completed before administering the
      questionnaire. The findings show that the Chinese version addressed adequately
      the original concepts and dimensions, and demonstrated a high level of
      equivalence with the original version. High internal consistencies (alpha = .80
      .92) of the scale and its subscales were found. Principal components factor
      analysis supported the existence of a five-factor structure. The Chinese version
      also demonstrated high sensitivity to family needs in terms of severity of
      illness and satisfactory correlations with theoretically related constructs.
      These findings support the potential of the Chinese version to be used as a
      diagnostic tool in assessment of family needs of Chinese patients.

PMID- 16287058
TI  - Nurse editors' views on the peer review process.
AB  - A growing body of research challenges the inter-rater reliability of peer
      reviewers and the value of reviewer training or blinding in improving the quality
      of manuscript reviews, but double-blinded peer review of papers remains a
      relatively unexamined standard for nursing journals. Using data from a larger
      emailed survey, the views of 88 nurse editors on peer review were analyzed using
      content analysis. The majority of nurse editors reported that blinding was
      important in peer review, to maintain objectivity and avoid negative personal or
      professional consequences. The minority who saw potential benefits of open review
      valued increased transparency in the reviewing and editorial decision-making
      process. An excellent review was viewed as containing specific instructions on
      how the deficits in a manuscript might be remedied. Common weaknesses of reviews
      were lack of specificity and inappropriate focus. Virtually all editors provided
      some form of preparation or guidance to reviewers. Peer review has an impact on
      nurses' workload and careers, and training in writing and critique should be
      included in nursing education.

PMID- 16287059
TI  - Letter to the editor.

PMID- 16287061
TI  - Interleukin-10 expression significantly correlates with minor CD8+ T-cell
      infiltration and high microvessel density in patients with gastric cancer.
AB  - We aimed to investigate the relationships between interleukin-10 (IL-10)
      expression and both the clinicopathological findings and prognoses in patients
      with gastric cancer and to compare IL-10 expression with microvessel (MV) density
      and CD8+ T lymphocyte infiltration to evaluate its effects on angiogenesis and
      immune responses in gastric cancer. IL-10 expression was determined in gastric
      cancer patients by reverse transcription-polymerase chain reaction (RT-PCR) or
      immunohistochemical procedures. Two of 7 normal gastric tissues showed IL-10 mRNA
      expression, while its expressions were confirmed in all advanced gastric
      carcinoma tissues examined (n=11) by RT-PCR. Immunohistochemical staining
      demonstrated that IL-10 expression was detected in 52 (47.7%) of 109 cases. There
      was a close correlation between IL-10 expression and MV density. IL-10 expression
      inversely correlated with CD8+ T-lymphocyte infiltration. The prognoses of
      patients whose tumors expressed IL-10 were significantly worse than those of
      patients whose tumors did not express IL-10. Multivariate analysis indicated IL
      10 expression was an independent prognostic factor. IL-10 might be associated
      with tumor progression by stimulating angiogenesis and suppressing immune
      responses in gastric cancer.

PMID- 16287060
TI  - Crystal structure of a heterodimer of phospholipase A2 from Naja naja sagittifera
      at 2.3 A resolution reveals the presence of a new PLA2-like protein with a novel
      cys 32-Cys 49 disulphide bridge with a bound sugar at the substrate-binding site.
AB  - The crystal structure of the phospholipase A2 (PLA2) heterodimer from Naja naja
      sagittifera reveals the presence of a new PLA2-like protein with eight disulphide
      bridges. The heterodimer is formed between a commonly observed group I PLA2
      having seven characteristic disulfide bonds and a novel PLA2-like protein (Cys
      PLA2) containing two extra cysteines at two highly conserved sites (positions 32
      and 49) of structural and functional importance. The crystals of the heterodimer
      belong to tetragonal space group P41212 with cell dimensions, a = b = 77.7 A and
      c = 68.4 A corresponding to a solvent content of 33%, which is one of the lowest
      values observed so far in the PLA2 crystals. The structure has been solved with
      molecular replacement method and refined to a final R value of 21.6% [Rfree =
      25.6%]. The electron density revealed the presence of cysteines 32 and 49 that
      are covalently linked to give rise to an eighth disulphide bridge in the PLA2
      like monomer. A non-protein high-quality electron density was also observed at
      the substrate-binding site in the PLA2-like protein that has been interpreted as
      N-acetylglucosamine. The overall tertiary folds of the two monomers are similar
      having all features of PLA2-type folding. A zinc ion is detected at the interface
      of the heterodimer with fivefold coordination while another zinc ion was found on
      the surface of Cys-PLA2 with sixfold coordination. The conformations of the
      calcium-binding loops of both monomers are significantly different from each
      other as well as from those in other group I PLA2s. The N-acetylglucosamine
      molecule is favorably placed in the substrate-binding site of Cys-PLA2 and forms
      five hydrogen bonds and several van der Waals interactions with protein atoms,
      thus indicating a strong affinity. It also provides clue of the possible
      mechanism of sugar recognition by PLA2 and PLA2-like proteins. The formation of
      heterodimer seems to have been induced by zinc ion.

PMID- 16287062
TI  - Mantle cell lymphomas acquire increased expression of CCL4, CCL5 and 4-1BB-L
      implicated in cell survival.
AB  - We have analyzed mantle cell lymphomas (MCLs), using high-density DNA
      microarrays, and confirmed the expression of differentially regulated antigens,
      using flow cytometry and immunohistochemistry. The results show that MCLs acquire
      expression of molecules that normally are involved in interaction with other
      immune cells and, thus, might affect the ability of the tumor to survive. The MCL
      signature is represented by the overexpression of the chemokine CCL4 (MIP-1beta),
      implicated in the recruitment of regulatory T cells, as well as CCL5 and 4-1BB-L.
      The latter molecules are normally involved in chemotaxis of T cells and B cell
      activation, respectively. Signaling through 4-1BB-L allows B cells to proliferate
      and the expression of its ligand, by the intra-tumoral mesh of follicular
      dendritic cells (FDC), could thus serve as a paracrine loop facilitating growth
      and survival of MCL cells.

PMID- 16287063
TI  - Abnormal methylation of the common PARK2 and PACRG promoter is associated with
      downregulation of gene expression in acute lymphoblastic leukemia and chronic
      myeloid leukemia.
AB  - The PARK2 gene, previously identified as a mutated target in patients with
      autosomal recessive juvenile parkinsonism (ARJP), has recently been found to be a
      candidate tumor suppressor gene in ovarian, breast, lung and hepatocellular
      carcinoma that maps to the third common fragile site (CFS) FRA6E. PARK2 is linked
      to a novel described PACRG gene by a bidirectional promoter containing a defined
      CpG island in its common promoter region. We have studied the role of promoter
      hypermethylation in the regulation of PARK2 and PACRG expression in different
      tumor cell lines and primary patient samples. Abnormal methylation of the common
      promoter of PARK2 and PACRG was observed in 26% of patients with acute
      lymphoblastic leukemia and 20% of patients with chronic myelogenous leukemia
      (CML) in lymphoid blast crisis, but not in ovarian, breast, lung, neuroblastoma,
      astrocytoma or colon cancer cells. Abnormal methylation resulted in
      downregulation of PARK2 and PACRG gene expression, while demethylation of ALL
      cells resulted in demethylation of the promoter and upregulation of PARK2 and
      PACRG expression. By FISH, we demonstrated that a lack of PARK2 and PACRG
      expression was due to biallelic hypermethylation and not to deletion of either
      PARK2 or PACRG in ALL. In conclusion, our results demonstrate for the first time
      that the candidate tumor suppressor genes PARK2 and PACRG are epigenetically
      regulated in human leukemia, suggesting that abnormal methylation and regulation
      of PARK2 and PACRG may play a role in the pathogenesis and development of this
      hematological neoplasm.

PMID- 16287064
TI  - Seventy-five years is an appropriate upper age limit for population-based
      mammography screening.
AB  - In this study, we assessed the results of the Dutch breast cancer screening
      programme for women aged 70-75, and discussed the current upper age limit of the
      women invited. We compared the main outcome parameters of the screening programme
      1998-2000 for women aged 70-75, with those in women aged 50-69. Breast cancer
      detection rates were also compared with prediction from 2 variants of a
      simulation model of breast cancer screening, assuming the mean sojourn time,
      i.e., the duration of the preclinical detectable phase, to increase or not with
      age above the age of 65. The underlying idea is that an increase of the sojourn
      time with age will lead to a less favourable balance between screening benefits
      and harms from a certain age on. Of the 315,103 women (aged 70-75) invited, 65.6%
      participated. The attendance increased from 1998 to 2000. For women aged 74 and
      75 years, this increase was almost 10%. As a result of the 187,207 screening
      examinations performed within this age group, 18.3 per 1,000 women were referred
      and 10.3 per 1,000 breast cancer were diagnosed. Detection rates in both initial
      and subsequent screens increased steadily with age and got close to those model
      simulated rates, which assume a continuously increasing sojourn time with age. A
      major finding of this study is that the screening participation among elderly
      women is high. The outcomes of our study suggest a steadily increasing sojourn
      time of breast tumours beyond the age of 69, leading to a strong increase in
      detection of cancers, and therefore, disfavouring the balance with the benefits
      of screening. At present, 75 years of age can be regarded as an appropriate upper
      age limit for the Dutch programme.

PMID- 16287065
TI  - Molecular analysis of the PI3K-AKT pathway in uterine cervical neoplasia:
      frequent PIK3CA amplification and AKT phosphorylation.
AB  - Uterine cervical carcinogenesis is probably dependent on cellular genetic damage
      in addition to the integration of high-risk HPV DNA in the epithelial cell
      genome. Gain of chromosome 3q24-29 is commonly observed in cervical neoplasia.
      The putative oncogene PIK3CA located in this region encodes a
      phosphatidylinositol 3-kinase (PI3K). In a process reversed by PTEN, PI3K
      generates inositol phospholipids that trigger AKT phosphorylation, which in turn
      effects tumor driving signals. We studied 46 specimens of formalin-fixed,
      paraffin-embedded cervical neoplastic tissue. The activation state of the PI3K
      AKT pathway was assessed immunohistochemically using an antibody with specificity
      towards serine 473-phosphorylated AKT. AKT phosphorylation was found in 39 out of
      46 examined specimens. To examine the possible molecular basis for this
      activation, we searched for PIK3CA amplification using quantitative real-time
      polymerase chain reaction. PIK3CA gene copy number was estimated to be 3 or more
      in 28 out of 40 successfully examined cases. Further, a PTEN mutation analysis of
      all 9 PTEN exons was carried out, but except for 1 metastasis with an exon 9
      V369I heterozygosity, all cases showed normal PTEN sequence. Immunohistochemical
      staining for PTEN was strong in all lesions. In conclusion, an increased
      activation state of AKT kinase appears to be present in cervical carcinogenesis,
      and may be accounted for by PIK3CA amplification, whereas PTEN mutation seems to
      be of little importance.

PMID- 16287066
TI  - High frequency of latent membrane protein-1 30-bp deletion variant with specific
      single mutations in Epstein-Barr virus-associated nasopharyngeal carcinoma in
      Moroccan patients.
AB  - Latent membrane protein 1 (LMP-1) is an Epstein-Barr virus-encoded oncoprotein
      expressed in approximately 50-70% of nasopharyngeal carcinoma (NPC). Previous
      studies have shown that NPC-derived LMP-1 variants carrying 30 bp deletion and
      specific mutations in the 3'C-terminal region confer high oncogenic potential and
      a weak immunogenicity. Although numerous polymorphism studies of LMP-1 have been
      carried out so far in the Asian population with NPC, very little is known in this
      regard on NPC patients from Northern Africa where there is a significantly high
      occurrence of this tumor. In our study, we examined the frequency of different
      LMP-1 sequence variants derived from Moroccan NPC patients. As compared to
      healthy donors, NPC patients showed a high prevalence of the 30bp deletion
      variant of LMP-1 (i.e. 84% vs. 36%; p<0.0005). Moreover, the del-LMP-1 variant
      derived from NPC tumors shared identical amino acid substitutions at positions
      322, 334, 338, 352 and 366 with the Mediterranean (Med) variant, whereas those
      derived from peripheral blood mononuclear cells (PBMC) had similar mutation
      pattern as China1 variant. Additional mutations within the 342-352 regions
      (identified in LMP-1 variants without deletion derived from NPC tumors) were not
      found in healthy donors' PBMC. Our results support the assumption that the
      distribution of LMP-1 variants in NPC tumors co-segregate with geographic
      regions. Indeed, Med variant is found more frequently in tumors from NPC Moroccan
      patients, whereas China1 variant is more prevalent in tumors from NPC patients in
      endemic regions for NPC.

PMID- 16287067
TI  - Adenovirus-mediated intra-tumoral delivery of the human endostatin gene inhibits
      tumor growth in nasopharyngeal carcinoma.
AB  - The growth and metastasis of nasopharyngeal carcinoma (NPC), one of the most
      common cancers in southern China, is closely related to neovascularization. Here,
      we examined whether intra-tumoral delivery of endostatin gene could lead to long
      term local expression of bioactive endostatin at therapeutic levels. We
      constructed a recombinant adenoviral vector carrying the human endostatin gene
      (Ad/hEndo), which expressed high-level endostatin protein in NPC CNE-2 cells, and
      significantly inhibited the proliferation and migration of vascular endothelial
      cells in vitro. Tumor growth and angiogenesis in NPC CNE-2 xenografted tumors
      were significantly inhibited after 5 courses of intra-tumoral treatment with
      Ad/hEndo in vivo. Endostatin mRNA in tumor tissues peaked at 1-2 days after intra
      tumoral administration and disappeared within 1 week, whereas the plasma
      endostatin protein levels peaked at 3 days after administration and lasted 2-3
      weeks. The therapeutically relevant endostatin transgene expression was achieved
      during the course of multiple intra-tumoral administrations with Ad/hEndo.
      Multiple injections with adenoviral vectors did not lead to continuous increases
      of adenovirus neutralizing antibodies in serum. Thus, adenovirus-mediated intra
      tumoral introduction of the human endostatin gene may form a viable new treatment
      for NPC, although readministration every 2-3 weeks may be necessary for the best
      effect.

PMID- 16287068
TI  - Differences in expression patterns of the tight junction proteins,claudin 1, 3, 4
      and 5, in human ovarian surface epithelium as compared to epithelia in inclusion
      cysts and epithelial ovarian tumours.
AB  - Human ovarian surface epithelium (OSE), regarded as the precursor cell of
      epithelial ovarian adenocarcinoma, is not a fully developed epithelium when
      situated on the ovarian surface. It lacks epithelial characteristics such as the
      cell-cell adhesion factor epithelial (E)-cadherin, but as we have shown earlier,
      this OSE can form functional tight junctions (TJs) in culture. Recent gene
      expression data on ovarian adenocarcinoma has pointed out a family of TJ
      proteins, the claudins, to be highly expressed in malignant compared to benign
      ovarian tumours. The purpose of this study was to investigate the distribution of
      claudin 1-5 proteins in cultured OSE (n=4), normal ovarian (n=11), benign (n=8),
      borderline (n=7) and ovarian cancer (n=22) tissues. We found that a weak or
      absence of expression of claudin 3 and claudin 4 in surface OSE changed to
      typical cell-border localisation in OSE of inclusion cysts in the normal ovarian
      stroma. Semiquantitative estimations of immunoblots showed that claudin 3 was
      significantly increased in ovarian adenocarcinomas compared to benign and
      borderline-type tumours. Claudin 4 was significantly increased in both borderline
      type and ovarian adenocarcinomas compared to benign tumours, whereas no changes
      were found for claudin 1 or 5. Concerning relation to Federation for
      International Gynaecology and Obstetrics (FIGO) grade, claudin 3, but not claudin
      4, was significantly increased in moderately, poorly and undifferentiated
      adenocarcinomas compared to well-differentiated and borderline-type tumours. No
      significant changes were noticed for any claudin with regard to FIGO stages. We
      conclude that both claudin 3 and 4, even though they differ in expression during
      ovarian malignant transformation, might be used as novel markers for ovarian
      tumours. The observations of lack of claudin 4 and low expression of claudin 3 in
      OSE strengthen our current knowledge about the biological nature of these cells
      as an undeveloped epithelium.

PMID- 16287069
TI  - Dominant-negative Rac increases both inherent and ionizing radiation-induced cell
      migration in C6 rat glioma cells.
AB  - Rho-like GTPases, including Cdc42, Rac1 and RhoA, regulate distinct actin
      cytoskeleton changes required for cell adhesion, migration and invasion. In the
      present study, we examined the role of Rac signaling in inherent migration, as
      well as radiation-induced migration, of rat glioma cells. Stable overexpression
      of dominant-negative Rac1N17 in a C6 rat glioma cell line (C6-RacN17) promoted
      cell migration, and ionizing radiation further increased this migration.
      Migration was accompanied by decreased expression of the focal adhesion molecules
      FAK and paxillin. Focal contacts and actin stress fibers were also reduced in C6
      RacN17 cells. Downstream effectors of Rac include JNK and p38 MAP kinases.
      Irradiation transiently activated p38, JNK and ERK1/2 MAP kinases in C6-RacN17
      cells, while p38 and JNK were constitutively activated in C6 control cells.
      Blocking JNK activity with JNK inhibitor SP600125 inhibited migration, suggesting
      that the JNK pathway may regulate radiation-induced, as well as inherent,
      migration of C6-RacN17 cells. Additionally, the radiation-induced migration
      increase was also inhibited by SB203580, a specific inhibitor of p38 MAP kinase.
      However, PD98059, a MEK kinase 1 inhibitor, failed to influence migration. This
      is the first evidence that suppression of Rac signaling may be involved in
      invasion or metastasis of glioma cells before and/or after radiotherapy. These
      data further suggest that radiotherapy for malignant glioma needs to be used with
      caution because of the potential for therapy-induced cell migration or invasion
      and that pharmacological inhibition of cell migration and invasion through
      targeting the Rac signaling pathway may represent a new approach for improving
      the therapeutic efficacy of radiotherapy for malignant glioma.

PMID- 16287070
TI  - Biallelic deletion within 16p13.13 including SOCS-1 in Karpas1106P mediastinal B
      cell lymphoma line is associated with delayed degradation of JAK2 protein.
AB  - Activity of Janus kinase 2 (JAK2) in the JAK2/STAT5 signaling pathway is
      critically controlled by suppressor of cytokine signaling-1 (SOCS-1). We have
      previously shown that SOCS-1 is biallelically mutated in the primary mediastinal
      B-cell lymphoma (PMBL) cell line MedB-1, resulting in impaired JAK2 degradation
      and sustained phospho-JAK2 action. SOCS-1 is frequently mutated in PMBL tumor
      primaries. Here, we report that the PMBL cell line Karpas1106P has a biallelic
      deletion of the SOCS-1 region on chromosome 16p13.13. By fluorescence in situ
      hybridization and microsatellite analysis, this deletion was narrowed down to a
      range of 650 kb to 1.48 Mb. Like MedB-1, Karpas1106P harbors gains of the JAK2
      gene on chromosomal region 9p24 and elevated levels of JAK2 mRNA. Nevertheless,
      JAK2 protein was not increased but constitutively phosphorylated in Karpas1106P
      cells. In analogy to MedB-1 cells, Karpas1106P cells exhibited a retarded
      degradation of de novo synthesized JAK2 protein revealed by pulse/chase
      experiments. Therefore, we conclude that loss of SOCS-1 function either by
      mutation or by the complete deletion of the gene plays an important role in the
      dysregulation of JAK/STAT signaling in Karpas1106P and PMBL.

PMID- 16287071
TI  - Quantitative analysis of aromatase mRNA expression derived from various promoters
      (I.4, I.3, PII and I.7) and its association with expression of TNF-alpha, IL-6
      and COX-2 mRNAs in human breast cancer.
AB  - The purpose of the present study was to study the aromatase mRNA expression as
      well as promoter usage (I.4, I.3, PII and I.7) in axillary adipose tissue (AA),
      mammary adipose tissue (MA), breast tumor tissue (BT) and adjacent normal breast
      tissue (NB), and to study the relationship between aromatase mRNA expression and
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and cyclooxygenase (COX)-2
      mRNA expression. BT (n=108), NB (n=54), AA (n=41) and MA (n=34) from patients
      with breast cancer were subjected to real-time PCR assays for the mRNA levels of
      aromatase, TNF-alpha, IL-6 and COX-2. We also studied the usage of promoters I.4,
      I.3, PII and the recently reported endothelial promoter I.7. Total aromatase mRNA
      levels were significantly up-regulated in BT as compared with NB, AA and MA.
      Proportion of promoter l.4-specific transcripts against the total transcripts was
      significantly decreased and that of promoter l.3- and l.7-specific transcripts
      was significantly increased in BT than NB, AA and MA. However, the amount of
      transcripts from all the 4 promoters was significantly up-regulated in BT than
      NB, AA and MA. Estrogen receptor-alpha (ER-alpha) positive tumors showed a higher
      percentage of promoter I.7 usage than ER-alpha negative tumors with a marginal
      significance (p=0.05), and tumor with high microvessel counts tended (p=0.06) to
      show a higher percentage of promoter I.7 usage than those with low microvessel
      counts. There was a significant association between aromatase mRNA levels and TNF
      alpha, IL-6 or COX-2 mRNA levels in BT, AA and MA but not in NB. These results
      suggest that enhanced transcription of promoters l.4, I.3, PII and I.7 explains
      the up-regulation of aromatase mRNA levels in BT. It has also been suggested that
      angiogenesis might stimulate the growth of ER-alpha positive tumors through the
      enhanced transcription of aromatase from promoter I.7 in endothelial cells in BT,
      and that TNF-alpha, IL-6 and COX-2 might be implicated in the up-regulation of
      aromatase mRNA in BT, AA and MA but not in NB.

PMID- 16287072
TI  - Prevalence of MYH germline mutations in Swiss APC mutation-negative polyposis
      patients.
AB  - In 10-30% of patients with classical familial adenomatous polyposis (FAP) and up
      to 90% of those with attenuated (<100 colorectal adenomas; AFAP) polyposis, no
      pathogenic germline mutation in the adenomatous polyposis coli (APC) gene can be
      identified (APC mutation-negative). Recently, biallelic mutations in the base
      excision repair gene MYH have been shown to predispose to a multiple adenoma and
      carcinoma phenotype. This study aimed to (i) assess the MYH mutation carrier
      frequency among Swiss APC mutation-negative patients and (ii) identify phenotypic
      differences between MYH mutation carriers and APC/MYH mutation-negative polyposis
      patients. Seventy-nine unrelated APC mutation-negative Swiss patients with either
      classical (n=18) or attenuated (n=61) polyposis were screened for germline
      mutations in MYH by dHPLC and direct genomic DNA sequencing. Overall, 7 (8.9%)
      biallelic and 9 (11.4%) monoallelic MYH germline mutation carriers were
      identified. Among patients with a family history compatible with autosomal
      recessive inheritance (n=45), 1 (10.0%) out of 10 classical polyposis and 6
      (17.1%) out of 35 attenuated polyposis patients carried biallelic MYH
      alterations, 2 of which represent novel gene variants (p.R171Q and p.R231H).
      Colorectal cancer was significantly (p<0.007) more frequent in biallelic mutation
      carriers (71.4%) compared with that of monoallelic and MYH mutation-negative
      polyposis patients (0 and 13.8%, respectively). On the basis of our findings and
      earlier reports, MYH mutation screening should be considered if all of the
      following criteria are fulfilled: (i) presence of classical or attenuated
      polyposis coli, (ii) absence of a pathogenic APC mutation, and (iii) a family
      history compatible with an autosomal recessive mode of inheritance.

PMID- 16287073
TI  - Molecular profiling of platinum resistant ovarian cancer.
AB  - The aim of this study is to discover a gene set that can predict resistance to
      platinum-based chemotherapy in ovarian cancer. The study was performed on 96
      primary ovarian adenocarcinoma specimens from 2 hospitals all treated with
      platinum-based chemotherapy. In our search for genes, 24 specimens of the
      discovery set (5 nonresponders and 19 responders) were profiled in duplicate with
      18K cDNA microarrays. Confirmation was done using quantitative RT-PCR on 72
      independent specimens (9 nonresponders and 63 responders). Sixty-nine genes were
      differentially expressed between the nonresponders (n=5) and the responders
      (n=19) in the discovery phase. An algorithm was constructed to identify
      predictive genes in this discovery set. This resulted in 9 genes (FN1, TOP2A,
      LBR, ASS, COL3A1, STK6, SGPP1, ITGAE, PCNA), which were confirmed with qRT-PCR.
      This gene set predicted platinum resistance in an independent validation set of
      72 tumours with a sensitivity of 89% (95% CI: 0.68-1.09) and a specificity of 59%
      (95% CI: 0.47-0.71)(OR=0.09, p=0.026). Multivariable analysis including patient
      and tumour characteristics demonstrated that this set of 9 genes is independent
      for the prediction of resistance (p<0.01). The findings of this study are the
      discovery of a gene signature that classifies the tumours, according to their
      response, and a 9-gene set that determines resistance in an independent
      validation set that outperforms patient and tumour characteristics. A larger
      independent multicentre study should further confirm whether this 9-gene set can
      identify the patients who will not respond to platinum-based chemotherapy and
      could benefit from other therapies.

PMID- 16287074
TI  - The leukocyte protein L-plastin induces proliferation, invasion and loss of E
      cadherin expression in colon cancer cells.
AB  - L-plastin, a gene that codes for an actin-bundling protein, is upregulated in the
      metastatic colon cancer cell line SW620, when compared to its premetastatic
      counterpart SW480. The aim of our study was to characterise the effect of L
      plastin overexpression on SW480 cells in the context of the acquisition of a
      metastatic phenotype. SW480 cell lines overexpressing L-plastin were established
      (SW480-LPL). Analysis of these cell lines revealed significantly higher rates of
      proliferation and invasion than the control cell line (SW480-Ctrl). In addition,
      the expression of E-cadherin was lost from SW480-LPL cells. Treatment of SW480
      LPL cells with cytochalasin B, an inhibitor of endocytosis, attenuated the loss
      of E-cadherin expression in these cells. The association of L-plastin
      overexpression with an increased rate of proliferation and invasion, and loss of
      E-cadherin expression in the SW480 colon cancer cell line indicates that L
      plastin plays an important mechanistic role in colorectal cancer metastasis
      (supplementary material for this article can be found on the International
      Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020
      7136/suppmat/index.html).

PMID- 16287075
TI  - A report on the current status of European research on the use of human
      papillomavirus testing for primary cervical cancer screening.
AB  - Cervical cancer remains a significant public health concern, both at a global and
      a European level. A number of new technologies such as diagnostic tests for human
      papillomavirus (HPV) have a potential to assist with the reduction of this
      disease. However, both the efficacy and the cost-effectiveness of these new
      technologies must be established in properly designed trials before they can be
      implemented within national public health programs. Our study reviews the
      randomized controlled trials that are currently being conducted in Europe to
      establish the performance of HPV testing as a primary cervical cancer screening
      test.

PMID- 16287076
TI  - Structure, conformational stability, and enzymatic properties of acylphosphatase
      from the hyperthermophile Sulfolobus solfataricus.
AB  - The structure of AcP from the hyperthermophilic archaeon Sulfolobus solfataricus
      has been determined by (1)H-NMR spectroscopy and X-ray crystallography. Solution
      and crystal structures (1.27 A resolution, R-factor 13.7%) were obtained on the
      full-length protein and on an N-truncated form lacking the first 12 residues,
      respectively. The overall Sso AcP fold, starting at residue 13, displays the same
      betaalphabetabetaalphabeta topology previously described for other members of the
      AcP family from mesophilic sources. The unstructured N-terminal tail may be
      crucial for the unusual aggregation mechanism of Sso AcP previously reported. Sso
      AcP catalytic activity is reduced at room temperature but rises at its working
      temperature to values comparable to those displayed by its mesophilic
      counterparts at 25-37 degrees C. Such a reduced activity can result from protein
      rigidity and from the active site stiffening due the presence of a salt bridge
      between the C-terminal carboxylate and the active site arginine. Sso AcP is
      characterized by a melting temperature, Tm, of 100.8 degrees C and an unfolding
      free energy, DeltaG(U-F)H2O, at 28 degrees C and 81 degrees C of 48.7 and 20.6 kJ
      mol(-1), respectively. The kinetic and structural data indicate that mesophilic
      and hyperthermophilic AcP's display similar enzymatic activities and
      conformational stabilities at their working conditions. Structural analysis of
      the factor responsible for Sso AcP thermostability with respect to mesophilic
      AcP's revealed the importance of a ion pair network stabilizing particularly the
      beta-sheet and the loop connecting the fourth and fifth strands, together with
      increased density packing, loop shortening and a higher alpha-helical propensity.

PMID- 16287077
TI  - Estradiol and its metabolites 4-hydroxyestradiol and 2-hydroxyestradiol induce
      mutations in human breast epithelial cells.
AB  - An elevated incidence of breast cancer in women has been associated with
      prolonged exposure to high levels of estrogens. Our laboratory demonstrated that
      treatment of the immortalized human breast epithelial cells MCF-10F with 17beta
      estradiol (E2), 4-hydroxyestradiol (4-OHE2) or 2-hydroxyestradiol (2-OHE2)
      induces phenotypical changes indicative of neoplastic transformation. MCF-10F
      cells treated with E2, 4-OHE2 or 2-OHE2 formed colonies in agar methocel and lost
      their ductulogenic capacity in collagen, expressing phenotypes similar to those
      induced by the carcinogen benzo[a]pyrene. To investigate whether the
      transformation phenotypes were associated with genomic changes, cells treated
      with E2, 4-OHE2 or 2-OHE2 at different doses were analyzed using microsatellite
      markers. Since microsatellite instability (MSI) and loss of heterozygosity (LOH)
      in chromosomes 13 and 17 have been reported in human breast carcinomas, we tested
      these parameters in MCF-10F cells treated with E2, 2-OHE2, or 4-OHE2 alone or in
      combination with the antiestrogen ICI182780. MCF-10F cells treated with E2 or 4
      OHE2, either alone or in combination with ICI182780, exhibited LOH in the region
      13q12.3 with the marker D13S893 located at approximately 0.8 cM telomeric to
      BRCA2. Cells treated with E2 or 4-OHE2 at doses of 0.007 and 70 nM and 2-OHE2
      only at a higher dose (3.6 microM) showed a complete loss of 1 allele with
      D13S893. For chromosome 17, differences were found using the marker TP53-Dint
      located in exon 4 of p53. Cells treated with E2 or 4-OHE2 at doses of 0.007 nM
      and 70 nM and 2-OHE2 only at a higher dose (3.6 microM) exhibited a 5 bp deletion
      in p53 exon 4. Our results show that E2 and its catechol estrogen metabolites are
      mutagenic in human breast epithelial cells. ICI182780 did not prevent these
      mutations, indicating that the carcinogenic effect of E2 is mainly through its
      reactive metabolites 4-OHE2 and 2-OHE2, with 4-OHE2 and E2 being mutagenic at
      lower doses than 2-OHE2.

PMID- 16287078
TI  - Expression of hiwi gene in human gastric cancer was associated with proliferation
      of cancer cells.
AB  - Stem cell genetics research may be critical to our understanding of
      carcinogenesis, as both stem cells and cancer cells possess the ability to self
      renew. Recent discoveries have indicated that the piwi family of genes plays an
      essential role in stem cell self-renewal in diverse organisms. The hiwi gene, the
      human homolog of the piwi family, participates in germ cell proliferation and its
      overexpression may cause the development of germ cell malignancy, but its
      expression and function in epithelial solid cancers have not been explored. In
      the present study, we investigated whether there was an association between hiwi
      expression and human gastric cancer and its potential mechanism. RT-PCR findings
      demonstrated that hiwi was expressed in different gastric cancer cell lines. To
      identify the HIWI protein in gastric cancer, we developed a specific monoclonal
      antibody against HIWI and immunohistochemistry was performed on various gastric
      tissues. We found that the expression ratio of hiwi in normal gastric tissues,
      atrophic gastritis, intestinal metaplasia and gastric cancers was 10% (5/50), 36%
      (18/50), 36% (18/50) and 76% (38/50), respectively, which was consistent with
      precancerous development. Notably, the expression pattern of hiwi in gastric
      cancer tissues was similar to that of Ki67, which was used as a marker of
      proliferation. Moreover, the suppression of hiwi by antisense or RNAi inhibited
      the growth of gastric cancer cells and induced cell cycle arrest in G2/M phase.
      These results suggest that hiwi may be involved in the development of gastric
      cancer and is a potential target for cancer therapy.

PMID- 16287079
TI  - Noise-enhanced balance control in patients with diabetes and patients with
      stroke.
AB  - OBJECTIVE: Somatosensory function declines with diabetic neuropathy and often
      with stroke, resulting in diminished motor performance. Recently, it has been
      shown that input noise can enhance human sensorimotor function. The goal of this
      study was to investigate whether subsensory mechanical noise applied to the soles
      of the feet via vibrating insoles can be used to improve quiet-standing balance
      control in 15 patients with diabetic neuropathy and 15 patients with stroke. Sway
      data of 12 healthy elderly subjects from a previous study on vibrating insoles
      were added for comparison. METHODS: Five traditional sway parameters and three
      sway parameters from random-walk analysis were computed for each trial (no noise
      or noise). RESULTS: Application of noise resulted in a statistically significant
      reduction in each of the eight sway parameters in the subjects with diabetic
      neuropathy, the subjects with stroke, and the elderly subjects. We also found
      that higher levels of baseline postural sway in sensory-impaired individuals was
      correlated with greater improvements in balance control with input noise.
      INTERPRETATION: This work indicates that noise-based devices could ameliorate
      diabetic and stroke impairments in balance control.

PMID- 16287080
TI  - Expression profiling of Wilms tumors reveals new candidate genes for different
      clinical parameters.
AB  - Wilms tumor is the most frequent renal neoplasm in children, but our
      understanding of its genetic basis is still limited. We performed cDNA microarray
      experiments using 63 primary Wilms tumors with the aim of detecting new candidate
      genes associated with malignancy grade and tumor progression. All tumors had
      received preoperative chemotherapy as mandated by the SIOP protocol, which sets
      this study apart from related approaches in the Unites States that are based on
      untreated samples. The stratification of expression data according to clinical
      criteria allowed a rather clear distinction between different subsets of Wilms
      tumors. Clear-cut differences in expression patterns were discovered between
      relapse-free as opposed to relapsed tumors and tumors with intermediate risk as
      opposed to high risk histology. Several differentially expressed genes,
      e.g.TRIM22, CENPF, MYCN, CTGF, RARRES3 and EZH2, were associated with Wilms tumor
      progression. For a subset of differentially expressed genes, microarray data were
      confirmed by real-time RT-PCR on the original set of tumors. Interestingly, we
      found the retinoic acid pathway to be deregulated at different levels in advanced
      tumors suggesting that treatment of these tumors with retinoic acid may represent
      a promising novel therapeutic approach.

PMID- 16287081
TI  - Managing and mining protein crystallization data.
AB  - The crystallization of macromolecules remains a major bottleneck in structural
      biology. The routine screening of more than one thousand crystallization
      conditions and subsequent optimization by fine screening presents a challenge to
      conventional laboratory notebook keeping. In addition, the development of high
      throughput robotic crystallization and imaging systems presents a pressing need
      for low-cost laboratory information management system (LIMS). Here we describe
      CLIMS2, a crystallization LIMS that features a simple, user-friendly graphical
      interface, allowing the storage, management, retrieval and mining of
      crystallization data. The CLIMS2 executable and documentation is freely available
      at http://clims.med.monash.edu.au.

PMID- 16287082
TI  - Is there an association between SV40 contaminated polio vaccine and
      lymphoproliferative disorders? An age-period-cohort analysis on Norwegian data
      from 1953 to 1997.
AB  - Between 1955 and 1963, an estimated number of 150 million people in various parts
      of the world, including Norway, received poliomyelitis vaccine possibly
      contaminated with infectious simian virus 40 (SV40). Human studies have
      investigated the hypothesised association between SV40 and various cancers, but
      the results have so far been contradicting. The aim of the present study was to
      examine Norwegian cancer incidence data to assess a possible association between
      birth cohorts assumed to have been subjected to the vaccine and the incidence
      rate of lymphoproliferative disorders (excluding Hodgkin's lymphoma), further
      subdivided into non-Hodgkin's lymphoma (NHL), lymphocytic leukemia and plasma
      cell neoplasms. Between 1953 and 1997, the incidence rate of lymphoproliferative
      diseases combined increased about 3-fold in both males and females. Subgroup
      analysis showed that this increase was largely attributable to NHL. Age-period
      cohort modelling of the subgroups, as well as of all groups combined, showed that
      the cohort effect was more prominent than the period effect. However, the
      variations in incidence patterns across the birth cohorts did not fit with the
      trends that would be expected if a SV40 contaminated vaccine did play a causative
      role. Thus, our data do not support the hypothesis of an association between the
      vaccine and any subgroup of lymphoproliferative diseases.

PMID- 16287083
TI  - Oxidation and inactivation of low molecular weight protein tyrosine phosphatase
      by the anticancer drug Aplidin.
AB  - The marine plitidepsin Aplidin derived from the Mediterranean tunicate Aplidium
      albicans is a strong apoptotic inducer with promising antitumor activity.
      However, little is known about the mechanism of action of the molecule. In this
      article, we report that Aplidin is cytotoxic for NIH3T3 cells and that its action
      is exerted through the production of reactive oxygen species (ROS). Rotenone, but
      not other selective inhibitors of ROS production, blocks the induction of ROS,
      suggesting the involvement of the mitochondrial respiratory chain in Aplidin
      action. The intracellular rise of redox potential caused by Aplidin inactivates
      several molecular targets. Among these targets, we focused our attention on
      protein tyrosine phosphatases (PTPs). In agreement with the well-characterized
      effect of ROS-mediated PTP oxidation, due to the presence of a cysteine residue
      in their catalytic site, we found that Aplidin induces a strong decrease in PTP
      activity. In particular, since the expression of low molecular weight-PTP (LMW
      PTP) is strongly associated with tumor onset and progression, we investigated the
      effect of Aplidin on this enzyme. Our data show that LMW-PTP is oxidized and
      inactivated during Aplidin treatment, thus causing a hyper-phosphorylation of its
      substrate beta-catenin. These findings demonstrate that, at least in part, the
      antitumoral activity of Aplidin could be due to the direct inhibition of LMW-PTP
      and its related oncogenic potential.

PMID- 16287084
TI  - Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated
      cancer in heavy drinkers.
AB  - Chronic alcohol consumption is associated with an increased risk for upper
      aerodigestive tract cancer and hepatocellular carcinoma. Increased acetaldehyde
      production via alcohol dehydrogenase (ADH) has been implicated in the
      pathogenesis. The allele ADH1C*1 of ADH1C encodes for an enzyme with a high
      capacity to generate acetaldehyde. So far, the association between the ADH1C*1
      allele and alcohol-related cancers among heavy drinkers is controversial. ADH1C
      genotypes were determined by polymerase chain reaction and restriction fragment
      length polymorphism in a total of 818 patients with alcohol-associated esophageal
      (n=123), head and neck (n=84) and hepatocellular cancer (n=86) as well as in
      patients with alcoholic pancreatitis (n=117), alcoholic liver cirrhosis (n=217),
      combined liver cirrhosis and pancreatitis (n=17) and in alcoholics without
      gastrointestinal organ damage (n=174). The ADH1C*1 allele and genotype ADH1C*1/1
      were significantly more frequent in patients with alcohol-related cancers than
      that in individuals with nonmalignant alcohol-related organ damage. Using
      multivariate analysis, ADH1C*1 allele frequency and rate of homozygosity were
      significantly associated with an increased risk for alcohol-related cancers
      (p<0.001 in all instances). The odds ratio for genotype ADH1C*1/1 regarding the
      development of esophageal, hepatocellular and head and neck cancer were 2.93 (CI,
      1.84-4.67), 3.56 (CI, 1.33-9.53) and 2.2 (CI, 1.11-4.36), respectively. The data
      identify genotype ADH1C*1/1 as an independent risk factor for the development of
      alcohol-associated tumors among heavy drinkers, indicating a genetic
      predisposition of individuals carrying this genotype.

PMID- 16287085
TI  - A point mutation in the NFYC gene generates an antigenic peptide recognized by
      autologous cytolytic T lymphocytes on a human squamous cell lung carcinoma.
AB  - We have identified an antigen recognized by cytolytic T lymphocytes (CTL) on the
      autologous tumor cells of a nonsmall cell lung cancer patient. The antigenic
      peptide, presented by HLA-B*5201 molecules, was encoded by a mutated sequence in
      the gene coding for the C subunit of transcription factor NF-Y. The mutation was
      present in the tumor sample from which the cell line was derived, and appeared to
      be unique to the tumor of this patient. In a lymph node draining the tumor,
      precursors of CTL recognizing the autologous tumor cells were detected at a
      frequency of about 1/30,000 of the CD8 cells, and 85% of them recognized the
      mutated NF-YC peptide, suggesting that the patient mounted a T cell response
      against this antigen. These results strengthened the notion that unique tumor
      specific antigens are highly represented not only in melanoma but also in other
      types of tumors, like nonsmall cell lung cancer.

PMID- 16287086
TI  - Comparison of the clinical significance of occult tumor cells in blood and bone
      marrow in breast cancer.
AB  - Immunocytochemical (ICC) detection of disseminated tumor cells (DTC) in bone
      marrow (BM) in early breast cancer is an independent prognostic factor. The
      significance of circulating tumor cells (CTC) in peripheral blood (PB) needs
      further exploration and comparison to DTC detection. PB and BM were prospectively
      collected from 341 breast cancer patients median 40 months after operation. PB
      samples were analyzed for tumor cells by a negative immunomagnetic technique
      (10x10(6) cells/test). BM aspirates were analyzed by standard ICC (2x10(6)
      cells/test). CTC were present in 10% of the patients and DTC in 14%. Thirty-seven
      relapses and 14 breast cancer deaths have occurred at median 66 months after
      diagnosis. Both CTC-status and DTC-status were significantly associated with
      disease free survival (DFS) (event rate: CTC-positive 26.5% vs. CTC-negative
      9.1%; DTC-positive 29.2% vs. DTC-negative 7.8%) (p<0.001/p<0.001, log rank) and
      breast cancer specific survival (event rate: CTC-positive 17.6% vs. CTC-negative
      2.6%; DTC-positive 12.5% vs. DTC-negative 2.7%) (p<0.001/p<0.001). The presence
      of both CTC and DTC (n=8) resulted in an especially poor prognosis (p<0.001). In
      node negative patients, DTC-status, but not CTC-status, predicted differences in
      DFS (p=0.006 vs. p=0.503). Excluding 23 patients with breast cancer-related
      events prior to the sample collections, CTC detection was not significantly
      associated with DFS/distant-DFS (p=0.158/0.193), in contrast to DTC detection
      (p<0.001/<0.001). Presence of CTC and absence of DTC did not affect DFS
      (p=0.516). Applied to early stage disease, CTC analysis of increased volumes of
      PB appears less sensitive and prognostic than standard DTC analysis. Currently,
      this does not support an exchange of BM with PB for analysis of occult tumor
      cells.

PMID- 16287088
TI  - Osteoprotegerin (OPG)--a potential new role in the regulation of endothelial cell
      phenotype and tumour angiogenesis?
AB  - The progression of cancer depends on the establishment of a tumour blood supply,
      and therefore tumour angiogenesis has been identified as a major target for new
      anticancer agents. Recent reports have suggested that osteoprotegerin (OPG) is
      involved in the control of endothelial cell survival through the inhibition of
      the activity of tumour necrosis factor- (TNF) related apoptosis-inducing ligand
      (TRAIL). The role of OPG in human tumour development and angiogenesis is
      currently unknown. In the present study we demonstrate the ability of OPG to
      support endothelial cell survival, as well as the formation of cord-like
      structures in vitro using a matrigel tubule formation assay. Investigation of
      various human cancers demonstrated endothelial OPG expression in 59% of malignant
      tumours (n=512), but in contrast, OPG was absent in endothelial cells associated
      with benign tumours and normal tissues (n=178). In a series of 400 breast
      tumours, endothelial OPG expression was associated with high tumour grade and
      certain histological types. Our data show a clear separation in endothelial OPG
      expression between malignant tumours and nonmalignant tissues, supporting a
      potential biological role for this molecule in the development and/or maintenance
      of the tumour vasculature. This is the first study to report the proangiogenic
      effects of OPG in vitro, as well as correlating expression of OPG by tumour
      endothelial cells with clinicopathological data in human tumours.

PMID- 16287089
TI  - Prediction of transporter family from protein sequence by support vector machine
      approach.
AB  - Transporters play key roles in cellular transport and metabolic processes, and in
      facilitating drug delivery and excretion. These proteins are classified into
      families based on the transporter classification (TC) system. Determination of
      the TC family of transporters facilitates the study of their cellular and
      pharmacological functions. Methods for predicting TC family without sequence
      alignments or clustering are particularly useful for studying novel transporters
      whose function cannot be determined by sequence similarity. This work explores
      the use of a machine learning method, support vector machines (SVMs), for
      predicting the family of transporters from their sequence without the use of
      sequence similarity. A total of 10,636 transporters in 13 TC subclasses, 1914
      transporters in eight TC families, and 168,341 nontransporter proteins are used
      to train and test the SVM prediction system. Testing results by using a separate
      set of 4351 transporters and 83,151 nontransporter proteins show that the overall
      accuracy for predicting members of these TC subclasses and families is 83.4% and
      88.0%, respectively, and that of nonmembers is 99.3% and 96.6%, respectively. The
      accuracies for predicting members and nonmembers of individual TC subclasses are
      in the range of 70.7-96.1% and 97.6-99.9%, respectively, and those of individual
      TC families are in the range of 60.6-97.1% and 91.5-99.4%, respectively. A
      further test by using 26,139 transmembrane proteins outside each of the 13 TC
      subclasses shows that 90.4-99.6% of these are correctly predicted. Our study
      suggests that the SVM is potentially useful for facilitating functional study of
      transporters irrespective of sequence similarity.

PMID- 16287087
TI  - The crystal structure of Aq_328 from the hyperthermophilic bacteria Aquifex
      aeolicus shows an ancestral histone fold.
AB  - The structure of Aq_328, an uncharacterized protein from hyperthermophilic
      bacteria Aquifex aeolicus, has been determined to 1.9 A by using multi-wavelength
      anomalous diffraction (MAD) phasing. Although the amino acid sequence analysis
      shows that Aq_328 has no significant similarity to proteins with a known
      structure and function, the structure comparison by using the Dali server reveals
      that it: (1) assumes a histone-like fold, and (2) is similar to an ancestral
      nuclear histone protein (PDB code 1F1E) with z-score 8.1 and RMSD 3.6 A over 124
      residues. A sedimentation equilibrium experiment indicates that Aq_328 is a
      monomer in solution, with an average sedimentation coefficient of 2.4 and an
      apparent molecular weight of about 20 kDa. The overall architecture of Aq_328
      consists of two noncanonical histone domains in tandem repeat within a single
      chain, and is similar to eukaryotic heterodimer (H2A/H2B and H3/H4) and an
      archaeal histone heterodimer (HMfA/HMfB). The sequence comparisons between the
      two histone domains of Aq_328 and six eukaryotic/archaeal histones demonstrate
      that most of the conserved residues that underlie the Aq_328 architecture are
      used to build and stabilize the two cross-shaped antiparallel histone domains.
      The high percentage of salt bridges in the structure could be a factor in the
      protein's thermostability. The structural similarities to other histone-like
      proteins, molecular properties, and potential function of Aq_328 are discussed in
      this paper.

PMID- 16287090
TI  - Inactivation of Id-1 in prostate cancer cells: A potential therapeutic target in
      inducing chemosensitization to taxol through activation of JNK pathway.
AB  - Resistance to anticancer drugs is the major problem in the treatment of many
      advanced cancers, including androgen-independent prostate cancer. Recently,
      increased expression of Id-1, a basic helix-loop-helix protein, is reported in
      several types of advanced cancer. It is suggested that high expression of Id-1
      may provide an advantage for cancer cell survival and inactivation of Id-1 may be
      able to increase cancer cells' susceptibility to apoptosis. To test this
      hypothesis, in this study, by using RNA interfering technology, we inactivated
      the Id-1 gene in 2 androgen-independent prostate cancer cell lines, DU145 and
      PC3, and investigated whether downregulation of Id-1 could lead to increased
      sensitivity to a commonly used anticancer drug, taxol. By using colony forming
      assay and MTT assay, we found that inactivation of Id-1 resulted in both
      decreased colony forming ability and cell viability in prostate cancer cells,
      after taxol treatment. In addition, the si-Id-1-induced sensitization to taxol
      was associated with activation of apoptosis pathway, which is demonstrated by
      increased apoptotic index, DNA laddering, sub-G1 phase of the cell cycle, as well
      as cleaved-PARP and Caspase 3. Furthermore, c-Jun N-terminal kinase (JNK), one of
      the common pathways responsible for taxol-induced apoptosis, was also activated
      in the si-Id-1 transfected cells. Inhibition of JNK activity by a specific
      inhibitor, SP600125, blocked the si-Id-1-induced sensitivity to taxol. These
      results indicate that increased Id-1 expression in prostate cancer cells may play
      a protective role against apoptosis, and downregulation of Id-1 may be a
      potential target to increase sensitivity of taxol-induced apoptosis in prostate
      cancer cells.

PMID- 16287091
TI  - Investigation of the functional three-dimensional anatomy of the human cystic
      duct: a single helix?
AB  - Clinical research into the formation of gallstones has indicated that the anatomy
      of the cystic duct is one of a number of factors contributing to the formation of
      gallstones. The cystic duct allows low-viscosity hepatic bile to enter the
      gallbladder under low pressure and the expulsion of a more viscous gallbladder
      bile, but little is known about this transport mechanism and the effect of
      anatomical variations in structure. This article describes the variation in
      geometry of the cystic duct, obtained from acrylic resin casts of the neck and
      first part of the cystic duct in gallbladders removed for gallstone disease and
      obtained from patients undergoing partial hepatectomy for metastatic disease. The
      data obtained allowed us to formulate a number of standard terms for describing
      cystic duct morphology and demonstrate that the term "spiral valve" is only
      partially correct when describing the duct anatomy. In over half of the casts,
      spiraling was not the dominant feature of the cystic duct. Additionally, the term
      valve implies active resistance to flow in one direction, whereas the internal
      baffles of the cystic duct would serve to regulate bile flow in both directions.
      These data are useful for realistic 3D modeling of fluid-structure interactions
      of the flow of bile in the human cystic duct.

PMID- 16287092
TI  - Soft tissue connection between rectus capitus posterior minor and the posterior
      atlanto-occipital membrane: a cadaveric study.
AB  - This investigation determined the variation, prevalence, tissue-type, and sex
      bias in the soft-tissue bridge between rectus capitis posterior minor (RCPMi) and
      the posterior atlanto-occipital membrane (PAO). Seventy-five cadavers (27 females
      and 48 males) were surveyed. When RCPMi was revealed, its superior attachment was
      detached and the muscle was reflected inferiorly to determine if it was attached
      to the underlying PAO. If a soft-tissue bridge was identified, the fibers found
      within the bridge were classified by visual inspection into three categories:
      tendon-like, muscle-like, and fascia-like. A fourth category of no attachment was
      also noted. These results show that RCPMi was present bilaterally in 93% of all
      cadavers surveyed (89% of the female cadavers and 96% of the male cadavers). On
      the right side, a soft-tissue bridge was present in 67% of males and 78% of
      females. On the left side, the soft-tissue bridge was present in 69% of males and
      82% of females. The number of male cadavers possessing tendon fibers in a soft
      tissue bridge was 56% on the right side and 55% on the left side. In females, the
      number of cadavers possessing tendon fibers in a soft-tissue bridge was 44% on
      the right side and 64% on the left side. In males, muscle fibers were present in
      the soft-tissue bridge, 34% on the right side and 36% on the left. In females,
      muscle fibers were found in the soft-tissue bridge, 43% on the right side and 36%
      on the left. There were no significant associations of sex and the presence of
      the soft-tissue bridge and a fiber-type within a soft-tissue bridge.

PMID- 16287094
TI  - Adsorption of charged albumin subdomains on a graphite surface.
AB  - We report some new molecular dynamics simulation results about the adsorption on
      a hydrophobic graphite surface of two albumin subdomains, each formed by three
      different alpha-helices, considering the correctly charged side groups at pH = 7
      instead of the neutral ones as done in our previous exploratory paper (Raffaini
      and Ganazzoli, Langmuir 2003;19:3403-3412). We find that the presence of charges
      affects somewhat the initial adsorption stage on the electrostatically neutral
      surface, but not the final one. Thus, we recover the result that a monolayer of
      aminoacids is eventually formed, with a rough parallelism of distant strands to
      optimize both the intramolecular and the surface interactions. This feature is
      consistent with the adsorption on the hydrophobic surface being driven by
      dispersion forces only, and with the "soft" nature of albumin. Additional
      optimizations of the final monolayer carried out at pH = 3 and 11 do not modify
      appreciably this picture, suggesting that adsorption on graphite is basically
      independent of pH. The enhanced hydration of the final adsorption state due to
      the (delocalized) charges of the side groups is also discussed in comparison with
      similar results of the neutralized subdomains.

PMID- 16287093
TI  - Conserved quantitative stability/flexibility relationships (QSFR) in an
      orthologous RNase H pair.
AB  - Many reports qualitatively describe conserved stability and flexibility profiles
      across protein families, but biophysical modeling schemes have not been available
      to robustly quantify both. Here we investigate an orthologous RNase H pair by
      using a minimal distance constraint model (DCM). The DCM is an all atom
      microscopic model [Jacobs and Dallakyan, Biophys J 2005;88(2):903-915] that
      accurately reproduces heat capacity measurements [Livesay et al., FEBS Lett
      2004;576(3):468-476], and is unique in its ability to harmoniously calculate
      thermodynamic stability and flexibility in practical computing times.
      Consequently, quantified stability/flexibility relationships (QSFR) can be
      determined using the DCM. For the first time, a comparative QSFR analysis is
      performed, serving as a paradigm study to illustrate the utility of a QSFR
      analysis for elucidating evolutionarily conserved stability and flexibility
      profiles. Despite global conservation of QSFR profiles, distinct enthalpy-entropy
      compensation mechanisms are identified between the RNase H pair. In both cases,
      local flexibility metrics parallel H/D exchange experiments by correctly
      identifying the folding core and several flexible regions. Remarkably, at
      appropriately shifted temperatures (e.g., melting temperature), these differences
      lead to a global conservation in Landau free energy landscapes, which directly
      relate thermodynamic stability to global flexibility. Using ensemble-based
      sampling within free energy basins, rigidly, and flexibly correlated regions are
      quantified through cooperativity correlation plots. Five conserved flexible
      regions are identified within the structures of the orthologous pair.
      Evolutionary conservation of these flexibly correlated regions is strongly
      suggestive of their catalytic importance. Conclusions made herein are
      demonstrated to be robust with respect to the DCM parameterization.

PMID- 16287095
TI  - Effects of Runx2 genetic engineering and in vitro maturation of tissue-engineered
      constructs on the repair of critical size bone defects.
AB  - Genetic and tissue engineering strategies are being pursued to address the
      clinical limitations of current bone grafting materials. Based on our previous
      work demonstrating that overexpression of the Runx2 osteoblastic transcription
      factor and in vitro construct maturation synergistically enhanced in vivo
      mineralization in an ectopic site (Byers et al., Tissue Eng 2004;10:1757-1766),
      we examined the effects of these two parameters on the repair of critical size
      bone defects. Primary rat bone marrow stromal cells transduced with Runx2 or
      control (no Runx2 insert) retroviral vector were seeded onto 3D fused deposition
      modeled polycaprolactone scaffolds. Runx2-modified cells produced biologically
      equivalent mineralized matrices at nearly 2-fold higher rates than control cells.
      Constructs cultured in vitro for 1 day (immature) or 21 days (mineralized) were
      subsequently implanted into critical size calvaria defects in syngeneic rats, and
      bone healing was analyzed by micro-CT and histomorphometry at 28 days. Runx2
      modified and control constructs precultured for 1 day healed to a greater extent
      than defects receiving no implant. Cell-free scaffolds yielded equivalent levels
      of bone formation as constructs precultured for 1 day. Interestingly, defects
      treated with control cell-seeded constructs precultured for 21 days exhibited low
      bone formation compared to other construct treatments, and repair was comparable
      to empty defects. In contrast, Runx2-modified constructs precultured for 21 days
      contained twice as much bone as control constructs precultured for 21 days and
      equivalent levels of new bone as cell-free and 1 day precultured constructs.
      These results demonstrate interplay between Runx2 genetically-modified cells and
      in vitro construct maturation in bone healing responses.

PMID- 16287096
TI  - Effect of filament diameter and extracellular matrix molecule precoating on
      neurite outgrowth and Schwann cell behavior on multifilament entubulation
      bridging device in vitro.
AB  - At present there is no clinically effective treatment for injuries or
      pathological processes that disrupt the continuity of axons in the mature central
      nervous system. However, a number of studies suggest that a tremendous potential
      exists for developing biomaterial based therapies. In particular, biomaterials in
      the form of bridging substrates have been shown to support at least some level of
      axonal regeneration across the lesion site, but display a limited capacity for
      directing axons toward their targets. To improve the directionality and outgrowth
      rate of the axonal regeneration process, filaments and tubes appear promising,
      but the technology is far from optimized. As a step toward optimization, the
      influence of filament diameter and various extracellular matrix coatings on nerve
      regeneration was evaluated in this article using a dorsal root ganglion (DRG)
      explant model. An increasing pattern of alignment and outgrowth of neurites in
      the direction parallel the long axis of the packed filament bundles with
      decreasing filament diameters ranging from supracellular and beyond (500 to 100
      mum), cellular (30 mum), down to subcellular size (5 mum) was observed. Such
      effects became most prominent on filament bundles with individual filament
      diameters in the range of cellular size and below (5 and 30 mum) where highly
      directional and robust neuronal outgrowth was achieved. In addition, laminin
      coated filaments that approached the size of spinal axons support significantly
      longer regenerative outgrowth than similarly treated filaments of larger
      diameter, and exceed outgrowth distance on similarly sized filaments treated with
      fibronectin. These data suggested the feasibility of using a multifilament
      entubulation bridging device for supporting directional axonal regeneration.

PMID- 16287097
TI  - Circulating EM66 is a highly sensitive marker for the diagnosis and follow-up of
      pheochromocytoma.
AB  - We have previously demonstrated that measurement of tissue concentration of the
      novel secretogranin II-derived peptide EM66 may help to discriminate between
      benign and malignant pheochromocytomas. The aim of the present study was to
      characterize EM66 in plasma and urine of healthy volunteers and pheochromocytoma
      patients, in order to further evaluate the usefulness of this peptide as a
      circulating marker for the management of the tumors. HPLC analysis of plasma and
      urine samples demonstrated that the EM66-immunoreactive material coeluted with
      the recombinant peptide. In healthy volunteers, plasma and urinary EM66 levels
      were, respectively, 2.6 (1.9-3.7) ng/ml and 2.9 (1.9-4.6) ng/ml. In patients with
      pheochromocytoma, plasma EM66 levels were 10-fold higher than those of healthy
      volunteers (26.9 (7.3-44) ng/ml), and returned to normal values after removal of
      the tumor. In contrast, urinary EM66 levels were not significantly different from
      those of healthy volunteers (3.2 (2.2-3.9) ng/ml). Measurement of total or free
      plasma metanephrines and 24 hr urinary metanephrines in our series of patients
      revealed that these tests, taken separately, are less sensitive than the EM66
      determination. Pheochromocytes in primary culture secreted high levels of EM66,
      suggesting that the chromaffin tumor was actually responsible for the increased
      plasma peptide concentrations in the patients. These data indicate that EM66 is
      secreted in the general circulation and that elevated plasma EM66 levels are
      correlated with the occurrence of pheochromocytoma. Thus, EM66 is a sensitive
      plasma marker that should be considered as a complementary tool in the management
      of pheochromocytoma.

PMID- 16287098
TI  - Mutation and polymorphism spectrum of the GALNS gene in mucopolysaccharidosis IVA
      (Morquio A).
AB  - Mucopolysaccharidosis IVA (MPS IVA; Morquio A disease) is an autosomal-recessive
      disorder caused by a deficiency of lysosomal N-acetylgalactosamine-6-sulfate
      sulfatase (GALNS; E.C.3.1.6.4). GALNS is required to degrade glycosaminoglycans,
      keratan sulfate (KS), and chondroitin-6-sulfate. Accumulation of undegraded
      substrates in lysosomes of the affected tissues leads to a systemic bone
      dysplasia. We summarize information on 148 unique mutations determined to date in
      the GALNS gene, including 26 novel mutations (19 missense, four small deletions,
      one splice-site, and two insertions). This heterogeneity in GALNS gene mutations
      accounts for an extensive clinical variability within MPS IVA. Seven
      polymorphisms that cause an amino acid change, and nine silent variants in the
      coding region are also described. Of the analyzed mutant alleles, missense
      mutations accounted for 78.4%; small deletions, 9.2%; nonsense mutation, 5.0%;
      large deletion, 2.4%; and insertions, 1.6%. Transitional mutations at CpG
      dinucleotides accounted for 26.4% of all the described mutations. The importance
      of the relationship between methylation status and distribution of transitional
      mutations at CpG sites at the GALNS gene locus was elucidated. The three most
      frequent mutations (over 5% of all mutations) were represented by missense
      mutations (p.R386C, p.G301C, and p.I113F). A genotype/phenotype correlation was
      defined in some mutations. Missense mutations associated with a certain phenotype
      were studied for their effects on enzyme activity and stability, the levels of
      blood and urine KS, the location of mutations with regard to the tertiary
      structure, and the loci of the altered amino acid residues among sulfatase
      proteins.

PMID- 16287099
TI  - Proteasome inhibitor MG132 sensitizes HPV-positive human cervical cancer cells to
      rhTRAIL-induced apoptosis.
AB  - In cervical carcinogenesis, the p53 tumor suppressor pathway is disrupted by HPV
      (human papilloma virus) E6 oncogene expression. E6 targets p53 for rapid
      proteasome-mediated degradation. We therefore investigated whether proteasome
      inhibition by MG132 could restore wild-type p53 levels and sensitize HPV-positive
      cervical cancer cell lines to apoptotic stimuli such as rhTRAIL (recombinant
      human TNF-related apoptosis inducing ligand). In a panel of cervical cancer cell
      lines, CaSki was highly, HeLa intermediate and SiHa not sensitive to rhTRAIL
      induced apoptosis. MG132 strongly sensitized HeLa and SiHa to rhTRAIL-induced
      apoptosis in a caspase-dependent and time-dependent manner. MG132 massively
      induced TRAIL receptor DR4 and DR5 membrane expression in HeLa, whereas in SiHa
      only DR5 membrane expression was upregulated from almost undetectable to high
      levels. Antagonistic DR4 antibody partially inhibited apoptosis induction by
      rhTRAIL and MG132 in HeLa but had no effect on apoptosis in SiHa. Inhibition of
      E6-mediated p53 proteasomal degradation by MG132 resulted in elevated levels of
      active p53 as demonstrated by p53 small interfering RNA (siRNA) sensitive p21
      upregulation. Although p53 siRNA partially inhibited MG132-induced DR5
      upregulation in HeLa and SiHa, no effect on rhTRAIL-induced apoptosis was
      observed. MG132 plus rhTRAIL enhanced caspase 8 and caspase 3 activation and
      concomitant cleavage of X-linked inhibitor of apoptosis (XIAP), particularly in
      HeLa. In addition, caspase 9 activation was only observed in HeLa. Downregulation
      of XIAP using siRNA in combination with rhTRAIL induced high levels of apoptosis
      in HeLa, whereas MG132 had to be added to the combination of XIAP siRNA plus
      rhTRAIL to induce apoptosis in SiHa. In conclusion, proteasome inhibition
      sensitized HPV-positive cervical cancer cell lines to rhTRAIL independent of p53.
      Our results indicate that not only DR4 and DR5 upregulation but also XIAP
      inactivation contribute to rhTRAIL sensitization by MG132 in cervical cancer cell
      lines. Combining proteasome inhibitors with rhTRAIL may be therapeutically useful
      in cervical cancer treatment.

PMID- 16287101
TI  - New species of woolly lemur Avahi (primates: lemuriformes) in Bemaraha (Central
      Western Madagascar).
AB  - There are at least three distinct taxa of woolly lemurs (genus Avahi) in western
      Madagascar. The range of Avahi occidentalis extends north and east of the
      Betsiboka River to the Bay of Narinda. Avahi unicolor occurs well to the north,
      including the Ampasindava peninsula and the Manongarivo Special Reserve. Here we
      describe a third Avahi population in central western Madagascar, which was
      discovered in the Bemaraha Strict Nature Reserve in the Tsingy de Bemaraha
      region, north of the Manambolo River. The description is based on a released type
      individual from which we obtained hair samples, photographs, and tape and video
      recordings. Its entire range is believed to be less than 5,000 km(2), and forest
      loss, along with an observed continuing decline in numbers, indicates that this
      species should be considered Endangered or even Critically Endangered, according
      to the Red List criteria of the World Conservation Union-IUCN.

PMID- 16287100
TI  - Effect of linker segments on the stability of epithelial cadherin Domain 2.
AB  - Epithelial cadherin is a transmembrane protein that is essential in calcium
      dependent cell-cell recognition and adhesion. It contains five independently
      folded globular domains in its extracellular region. Each domain has a seven
      strand beta-sheet immunoglobulin fold. Short seven-residue peptide segments
      connect the globular domains and provide oxygens to chelate calcium ions at the
      interface between the domains (Nagar et al., Nature 1995;380:360-364). Recently,
      stability studies of ECAD2 (Prasad et al., Biochemistry 2004;43:8055-8066) were
      undertaken with the motivation that Domain 2 is a representative domain for this
      family of proteins. The definition of a domain boundary is somewhat arbitrary;
      hence, it was important to examine the effect of the adjoining linker regions
      that connect Domain 2 to the adjacent domains. Present studies employ temperature
      denaturation and proteolytic susceptibility to provide insight into the impact of
      these linkers on Domain 2. The significant findings of our present study are
      threefold. First, the linker segments destabilize the core domain in the absence
      of calcium. Second, the destabilization due to addition of the linker segments
      can be partially reversed by the addition of calcium. Third, sodium chloride
      stabilizes all constructs. This result implies that electrostatic repulsion is a
      contributor to destabilization of the core domain by addition of the linkers.
      Thus, the context of Domain 2 within the whole molecule affects its thermodynamic
      characteristics.

PMID- 16287102
TI  - Multiplexed microsatellites for rapid identification and characterization of
      individuals and populations of Cercopithecidae.
AB  - Cross-amplification of 15 human microsatellites was performed successfully in
      cynomolgus (Macaca fascicularis) and rhesus (M. mulatta) macaques and 11 other
      Cercopithecidae species of biomedical and conservation relevance. To allow for
      quick, efficient, and high-throughput genotyping to assess intra- and
      interspecific genetic variation, we performed three multiplex sets, each
      comprised of five markers from different parts of the genome (i.e., autosomes,
      the MHC region, and the X-chromosome). These multiplex sets are likely to reveal
      allelic divergence between taxa, which could be used for their discrimination.
      Population studies on three regional populations of M. fascicularis and one of M.
      mulatta revealed that most of the loci, with the exception of one monomorphic
      locus, displayed polymorphisms (the expected heterozygosities were 0.48-0.91 for
      M. fascicularis, and 0.61-0.93 for M. mulatta), which makes them useful for
      population genetics. For the multiplex set M1, including the nonlinked autosomal
      markers, low probabilities of identity were observed: P(ID) values ranged from 8
      x 10(-7) to 3 x 10(-5). This multiplex set is reliable for forensic applications,
      such as individual identification, parentage testing, and kinship analysis, in
      wild and captive populations.

PMID- 16287103
TI  - Fifty years of chimpanzee demography at Taronga Park Zoo.
AB  - There has been a captive Pan troglodytes colony at Taronga Park Zoo in Sydney,
      Australia, since the mid-1930s. Demographic data on these animals were first
      analyzed in 1986; however, further information collected for 15 years since then
      is now available. The reproductive histories of 33 females in the colony have
      been recorded, and these data form the largest collection of captive chimpanzee
      data from a setting that has involved natural breeding conditions since the mid
      1960s. These data were analyzed in conjunction with data from wild populations to
      establish the degree of variability present within chimpanzee reproductive
      parameters, and to identify which distinctive life history characteristics
      persist in well-provisioned, natural-fertility populations. The age at first
      birth for the chimpanzee females is 9.8 yr on average (n=16), which is 1-4.8 yr
      earlier than the average for wild populations. In line with this accelerated
      reproduction, birth intervals are also significantly shorter than those in
      noncaptive chimpanzee populations. The median birth interval for all surviving
      infants (based on a Kaplan-Meier survival analysis) is 49 months (n=43) compared
      to 62+ months for wild groups. At the same time, infant mortality remains high.
      The data confirm distinctive features of the life history of common chimpanzees,
      including later maturation, long birth intervals, a relatively invariant
      fertility schedule, and high juvenile mortality. However, aspects of both
      fertility and mortality are significantly related to social circumstances,
      indicating that in common chimpanzees, as in humans, life history characters may
      represent ecological and social adaptations rather than species-fixed
      characteristics.

PMID- 16287104
TI  - Mechanical properties of foods used in experimental studies of primate
      masticatory function.
AB  - In vivo studies of jaw-muscle behavior have been integral factors in the
      development of our current understanding of the primate masticatory apparatus.
      However, even though it has been shown that food textures and mechanical
      properties influence jaw-muscle activity during mastication, very little effort
      has been made to quantify the relationship between the elicited masticatory
      responses of the subject and the mechanical properties of the foods that are
      eaten. Recent work on human mastication highlights the importance of two
      mechanical properties-toughness and elastic modulus (i.e., stiffness)-for food
      breakdown during mastication. Here we provide data on the toughness and elastic
      modulus of the majority of foods used in experimental studies of the nonhuman
      primate masticatory apparatus. Food toughness ranges from approximately 56.97 Jm(
      2) (apple pulp) to 4355.45 Jm(-2) (prune pit). The elastic modulus of the
      experimental foods ranges from 0.07 MPa for gummy bears to 346 MPa for popcorn
      kernels. These data can help researchers studying primate mastication select
      among several potential foods with broadly similar mechanical properties.
      Moreover, they provide a framework for understanding how jaw-muscle activity
      varies with food mechanical properties in these studies.

PMID- 16287105
TI  - Seasonality, body condition, and timing of reproduction in Propithecus verreauxi
      verreauxi in the Kirindy Forest.
AB  - Mammals that live in seasonal environments may adjust their reproductive cycles
      to cope with fluctuations in food availability. Because lemurs in Madagascar
      experience highly seasonal variation in food availability, we examined the
      effects of fluctuating food availability on body condition and reproduction in
      one of the larger living species, Verreaux's sifaka (Propithecus verreauxi
      verreauxi), in the Kirindy Forest of western Madagascar. Seven years of
      demographic data were combined with an intensive study of 25 individuals over the
      course of 18 months. In contrast to other populations of Verreaux's sifaka,
      females were found to have greater body mass than males. Both male and female
      sifaka exhibited significant losses of body mass and fat during the dry season.
      Females were more likely to give birth and successfully wean an infant when they
      had higher body mass during the mating season. They mated during the periods of
      high and declining food availability, gave birth during the lean season, and then
      timed mid/late lactation with the period of increasing food availability. Thus,
      we conclude that sifaka follow the "classic" reproductive strategy (sensu van
      Schaik and van Noordwijk [Journal of Zoology (London) 206:533-549, 1985]).

PMID- 16287106
TI  - Are Kirindy sifaka capital or income breeders? It depends.
AB  - The capital and income breeding framework has only recently been used to explain
      variation in female reproductive strategies in primates. The application of this
      framework to primates and other mammals with long reproductive cycles has not
      been consistent. We evaluated data on Verreaux's sifaka (Propithecus verreauxi
      verreauxi) in the Kirindy Forest of western Madagascar to determine whether they
      are capital or income breeders. We found that Verreaux's sifaka can be classified
      as either capital or income breeders, depending on how these concepts are
      operationalized. These conflicting findings highlight why the capital/income
      framework is currently problematic and must be standardized if it is to be a
      useful framework for primatologists.

PMID- 16287108
TI  - Anatomy 102: a synthesis.

PMID- 16287107
TI  - A panel of 20 highly variable microsatellite polymorphisms in rhesus macaques
      (Macaca mulatta) selected for pedigree or population genetic analysis.
AB  - This paper reports 20 new microsatellite loci that are highly polymorphic in
      rhesus macaques (Macaca mulatta). We screened known human microsatellite loci to
      identify markers that are polymorphic in rhesus macaques, and then selected
      specific loci that show substantial levels of heterozygosity and robust, reliable
      amplification. The 20 loci reported here were chosen to include one highly
      informative microsatellite from each rhesus monkey autosomal chromosome. Fourteen
      of the 20 polymorphisms are tetranucleotide repeats, and all can be analyzed
      using standard PCR and electrophoresis procedures. These new rhesus markers have
      an average of 15.5 alleles per locus and average heterozygosity of 0.83. This
      panel of DNA polymorphisms will be useful for a variety of different genetic
      analyses, including pedigree testing, paternity analysis, and population genetic
      studies. Many of these loci are also likely to be informative in other closely
      related Old World monkey species.

PMID- 16287109
TI  - Practical light embalming technique for use in the surgical fresh tissue
      dissection laboratory.
AB  - Surgeons using a fresh tissue dissection laboratory need specimens with tissue
      color and texture as close as possible to those of a living body. Completely
      unembalmed specimens kept in a cooler remain in good condition only for a few
      days, and then decay rapidly. Unembalmed specimens can be frozen for later use,
      but freezing harms their texture, and decay is suspended only for as long as they
      remain frozen. Since 1998, we have used a method of light embalming adapted from
      funeral home techniques, on over 250 cadavers used in our fresh tissue dissection
      laboratory. Lightly embalmed cadavers can be kept in a cooler for up to 6 weeks
      before use, with negligible loss of tissue quality and color. Once dissection is
      begun, the cadavers remain in excellent condition, free from odor, for at least
      two further weeks. Light embalming overcomes the practical problems seen with
      completely unembalmed specimens, avoids the use of freezing, and extends the
      range of activities that can be planned in the laboratory. This paper presents
      details of the light embalming technique. We assume that light embalming does not
      kill all transmissible pathogens.

PMID- 16287110
TI  - Male mating strategies and reproductive constraints in a group of wild tufted
      capuchin monkeys (Cebus apella nigritus).
AB  - Tufted capuchin monkeys (Cebus apella) provide an extreme example of active
      female sexual solicitation of males. In spite of being targeted by females for
      sex, males may delay copulation for hours or days. Data were collected on the
      sexual interactions in one wild capuchin group at the Estacao Biologica de
      Caratinga in Brazil from September 1996 to August 1997. All successful
      conceptions during this year occurred in the dry season, yet sexual behavior was
      observed during 9 months of the year. This study tested whether male sexual
      response to female proceptivity was seasonally-mediated. Male consortship
      participation, solicitation of females, latency to copulation, and copulation
      frequency were compared between fertile and nonconceptive females. Seasonal
      patterns in copulation interference, mating style, and alternative mating
      strategies were also examined. Thirty-two copulations were observed. The alpha
      male was solicited for significantly more consortship days per female, but his
      mating success, in terms of copulation frequency, did not differ from that of two
      other adult males in the group. In the dry season, when the females were fertile,
      the males showed increased contest competition for mates, a higher frequency of
      alternative mating strategies against copulation interference, and increased
      monitoring of the females' condition. However, contrary to expectations, the
      alpha male's latency to copulation was significantly longer in the fertile season
      than in the nonconceptive months, and no males were observed to mate more than
      one time per day, even at the conceptive peak. Male mating strategies were
      affected by both season and rank, and there was evidence for reproductive
      constraints on males throughout the year. Limited male ejaculatory capacity and
      male choice in the timing of copulations within female proceptive phases may both
      be important factors in driving the sexual dynamics of this species.

PMID- 16287112
TI  - Detection of a new mutation in KIT exon 9 in a gastrointestinal stromal tumor.
AB  - Gastrointestinal stromal tumors are mesenchymal tumors arising in the stomach and
      small bowel and more rarely in the rectum, esophagus, peritoneum and
      retroperitoneum. These tumors are characterized by KIT or PDGFRA mutations. KIT
      mutations are all in frame and lead to constitutive tyrosine kinase domain
      activation without ligand binding. Mutations concern four exons (9, 11, 13 and
      17) but mainly exon 11. We report a new mutation in exon 9, since only AY 502-503
      duplication/insertion, FAF 506 insertion and P456S substitution have been
      previously reported. This mutation consists of a large deletion of 43 nucleotides
      and an insertion of 25 nucleotides. More surprisingly, the sequence inserted
      corresponds to the complementary sequence of the wild allele but in the opposite
      sense. To our knowledge, this mutation has never been previously described.

PMID- 16287111
TI  - Morphometric study of the external and middle ear anatomy in sheep: a possible
      model for ear experiments.
AB  - Sheep are a potentially useful model for otologic surgical training and
      experimentation, currently limited by the scarcity of morphological comparisons
      between the structure of the ear in sheep and in humans. A detailed morphometric
      study of the ear in sheep was carried out using computed tomography. Measurements
      made with AutoCAD Release 14 were compared with measurements for the human ear
      reported in the literature. In general, ear structures in sheep are two-thirds
      the size of those in humans. The important anatomical similarities found in this
      study between the ear in sheep and in humans suggest that sheep may be a useful
      model for surgical training and experimentation in some middle ear procedures.

PMID- 16287113
TI  - High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome.
AB  - Germline mutations in the STK11 gene have been identified in 10-70% of patients
      with Peutz-Jeghers syndrome (PJS), an autosomal-dominant hamartomatous polyposis
      syndrome. A second locus was assumed in a large proportion of PJS patients. To
      date, STK11 alterations comprise mainly point mutations; only a small number of
      large deletions have been reported. We performed a mutation analysis for the
      STK11 gene in 71 patients. Of these, 56 met the clinical criteria for PJS and 12
      were presumed to have PJS because of mucocutaneous pigmentation only or bowel
      problems due to isolated PJS polyps. No clinical information was available for
      the remaining three patients. By direct sequencing of the coding region of the
      STK11 gene, we identified point mutations in 37 of 71 patients (52%). We examined
      the remaining 34 patients by means of the multiplex ligation-dependent probe
      amplification (MLPA) method, and detected deletions in 17 patients. In four
      patients the deletion extended over all 10 exons, and in eight patients only the
      promoter region and exon 1 were deleted. The remaining deletions encompassed
      exons 2-10 (in two patients), exons 2-3, exons 4-5, or exon 8. When only patients
      who met the clinical criteria for PJS are considered, the overall mutation
      detection rate increases to 94% (64% point mutations and 30% large deletions). No
      mutation was identified in any of the 12 presumed cases. In conclusion, we found
      that approximately one-third of the patients who met the clinical PJS criteria
      exhibited large genomic deletions that were readily detectable by MLPA. Screening
      for point mutations and large deletions by direct sequencing or MLPA,
      respectively, increased the mutation detection rate in the STK11 gene up to 94%.
      There may be still other mutations in the STK11 gene that are not detectable by
      the methods applied here. Therefore, it is questionable whether a second PJS
      locus exists at all.

PMID- 16287114
TI  - Left subclavian artery.

PMID- 16287115
TI  - Molecular surface generation using a variable-radius solvent probe.
AB  - Protein-ligand binding occurs through interactions at the molecular surface.
      Hence, a proper description of this surface is essential to our understanding of
      the process of molecular recognition. Recent studies have noted the inadequacy of
      using a fixed 1.4 A solvent probe radius to generate the molecular surface. This
      assumes that water molecules approach all surface atoms at an equal distance
      irrespective of polarity, which is not the case. To adequately model the protein
      water boundary requires that the solvent probe radius change according to the
      polarity of its contacting atoms, smaller near polar atoms and larger near apolar
      atoms. To our knowledge, no method currently exists to generate the molecular
      surface of a protein in this manner. Using a modification of the marching
      tetrahedra algorithm, we present a method to generate molecular surfaces using a
      variable radius solvent probe. The resulting surface lacks many of the
      unrealistic small crevices in nonpolar regions that are found when utilizing an
      invariant 1.4 A solvent probe, while maintaining the fine detail of the surface
      at polar regions. On application of the method on a test set of 20 protein
      structures taken from the Protein Data Bank (PDB), we also find far fewer empty
      unsolvated cavities that are present when using only a 1.4 A solvent probe, while
      the majority of solvated and polar cavities is retained. This suggests that the
      majority of empty cavities previously observed in protein structures might simply
      be artifacts of the surfacing method. We also find that the variable probe
      surface can have significant effects on electrostatic calculations by generating
      a better tuned description of the protein-water boundary. We also examined the
      binding interfaces of a diverse set of 55 protein-protein complexes. We find that
      using a variable probe results in an increase in perceived shape complementarity
      at these sites compared to using a 1.4 A solvent probe. The molecular volume and
      surface area are geometric values that determine various important properties for
      macromolecules, and the altered description afforded by a variable solvent probe
      molecular surface can have significant implications in protein recognition,
      energetics, folding, and stability calculations.

PMID- 16287116
TI  - Assessing protein disorder and induced folding.
AB  - Intrinsically disordered proteins (IDPs) defy the structure-function paradigm as
      they fulfill essential biological functions while lacking well-defined secondary
      and tertiary structures. Conformational and spectroscopic analyses showed that
      IDPs do not constitute a uniform family, and can be divided into subfamilies as a
      function of their residual structure content. Residual intramolecular
      interactions are thought to facilitate binding to a partner and then induced
      folding. Comprehensive information about experimental approaches to investigate
      structural disorder and induced folding is still scarce. We herein provide hints
      to readily recognize features typical of intrinsic disorder and review the
      principal techniques to assess structural disorder and induced folding. We
      describe their theoretical principles and discuss their respective advantages and
      limitations. Finally, we point out the necessity of using different approaches
      and show how information can be broadened by the use of multiples techniques.

PMID- 16287117
TI  - High incidence of the os peroneum in a cadaver sample in Johannesburg, South
      Africa: possible clinical implications?
AB  - This study set out to investigate the incidence of the os peroneum in a cadaver
      sample from Johannesburg, South Africa and to note how bio-demographic parameters
      affect such incidence. The os peroneum (OP) is a sesamoid bone frequently found
      in the tendon of the fibularis longus muscle (FLM), as it passes on the plantar
      aspect of the cuboid bone. While this bone is often an incidental dissection room
      or radiological finding, OP fractures, with or without associated rupture of the
      fibularis (peroneus) longus tendons have been reported. Some investigators have
      also suggested that the presence of the OP may render the tendon of the FLM
      susceptible to avulsion injuries. The reported incidences of the OP range between
      8 and 26%. These data have emanated by and large from radiographic rather than
      dissection studies, and the influences of biological indices such as age, sex,
      population group of origin, and side of the body on these incidences remain
      largely unknown. Forty cadavers (average age = 75 years) were dissected. Os
      peronei were present in 36 of these cadavers (90.0%), with 96% of them occurring
      bilaterally. This bilateral incidence was statistically significant (P = 0.007),
      but there was no significant difference in age (P = 0.38), sex (P = 0.97), or
      population group (P = 0.17). We hope that the unusually high incidence of the OP
      reported here will stimulate further research into possible predisposing factors
      as well as into the speculated associations between sesamoid occurrence,
      osteoarthritis, and tendon injuries.

PMID- 16287118
TI  - A computational protocol to probe the role of solvation effects on the reduction
      potential of azurin mutants.
AB  - Semiquantitative relationships between thermodynamic parameters of Cu2+ reduction
      experimentally measured for a series of azurin mutants and the solvation free
      energy of the oxidized state of the proteins were derived. Solvation free energy
      calculations were carried out within an ONIOM/PCM scheme specifically adapted to
      this protein series. The method proved to be able to capture the main
      determinants of the measured reduction parameters, providing satisfactory
      predictions of the E degrees '.

PMID- 16287119
TI  - Functional role of a protein foldon--an Omega-loop foldon controls the alkaline
      transition in ferricytochrome c.
AB  - Hydrogen exchange results for cytochrome c and several other proteins show that
      they are composed of a number of foldon units which continually unfold and refold
      and account for some functional properties. Previous work showed that one Omega
      loop foldon controls the rate of the structural switching and ligand exchange
      behavior of cytochrome c known as the alkaline transition. The present work tests
      the role of foldons in the alkaline transition equilibrium. We measured the
      effects of denaturant and 14 destabilizing mutations. The results show that the
      ligand exchange equilibrium is controlled by the stability of the same foldon
      unit implicated before. In addition, the results obtained confirm the epsilon
      amino group of Lys79 and Lys73 as the alkaline replacement ligands and bear on
      the search for a triggering group.

PMID- 16287120
TI  - Crystal structure of dihydrodipicolinate synthase (BA3935) from Bacillus
      anthracis at 1.94 A resolution.

PMID- 16287121
TI  - Mechanical contribution of the fibula to torsion stiffness in the lower
      extremity.
AB  - The role of the fibula in rotational stability of the lower extremity, taking
      into account the intact knee joint and tibia, to the best of our knowledge, has
      not been investigated. A cadaver study was designed to determine the torque
      transfer down the lower extremity, with and without the fibula. Six fresh, frozen
      human cadaver legs were used. The knee joint was left intact and the foot
      disarticulated. An external rotation up to 5 degrees , coupled with axial
      compression, was applied to the femur passing through the knee joint in extension
      and down the lower extremity to the fixed distal end, where torque (N m) was
      measured via a load cell. Each specimen was further tested with the fibula, cut 4
      cm from the distal end, and finally with the entire fibula disarticulated at the
      proximal end and removed. To achieve 5 degrees rotation, torques reached 1.82 N m
      (SD, 0.66 N m). When the fibula was cut, the torque reduced a small yet
      significant amount of 5%. With the entire fibula removed, the torque reduction
      was significant and more pronounced at 11%. The fibula provided a small yet
      significant role in torsion stability. From this study, where the biomechanical
      characteristics of the fibula is explicated, it is hoped that this information
      will have use in further understanding the biomechanical role of the fibula,
      especially, in relation to the altered mechanics associated with lower limb
      pathology involving a deficient fibula.

PMID- 16287123
TI  - Clinical anatomy for high school students.

PMID- 16287124
TI  - Anatomical examination of the recurrent artery of Heubner.
AB  - There is considerable inconsistency in the description of the origins,
      dimensions, and course of the recurrent artery of Heubner (RAH). The RAH
      frequently supplies parts of the basal ganglia and the anterior limb of the
      internal capsule and can be damaged with improper clip placement during repair of
      aneurysms near the anterior communicating artery. Thus, further elaboration of
      the anatomical descriptions of the RAH is necessary. The gross anatomy of the RAH
      was studied in 69 human brain hemispheres. RAH was found as a single vessel in 53
      hemispheres (77%), as double arteries in 12 hemispheres (17%), and was absent in
      4 hemispheres (6%). The origin of the RAH was from the junction of the anterior
      cerebral artery and anterior communicating artery in 48 (62.3%) hemispheres, from
      the proximal A2 segment of the anterior cerebral artery in 18 (23.3%) hemispheres
      and from the A1 segment in 11 (14.3%) hemispheres. The diameters of the artery
      ranged from 0.2 to 1.3 mm with a mean of 0.8 mm, while the length ranged from 0.9
      to 3.8 cm with a mean of 2.4 cm. The above data may provide important information
      to neurosurgeons operating in this area, as well as to neuroanatomists teaching
      the vascular supply of the brain.

PMID- 16287125
TI  - "C3, C4, C5 keep you alive," or do they?
AB  - Contrary to traditional teaching in anatomy courses, historical data suggest that
      bilateral loss of phrenic nerve function does not necessarily result in death.

PMID- 16287126
TI  - Anatomy of the sigmoid colon, rectum, and the rectovaginal pouch in women with
      enterocele and anterior rectal wall procidentia.
AB  - This study describes the anatomy of the rectovaginal pouch, the sigmoid colon,
      and rectum in women with posterior enterocele and anterior rectal wall
      procidentia. The anatomy of rectovaginal pouch, sigmoid colon, and rectum was
      described in 36 women with an enterocele (group A) and compared with those of 43
      women (group B) without pelvic organ prolapse. Women with previous incontinence
      or prolapse surgery were excluded. The mean age in group A was 58 years (40-75)
      and in group B 35 years (19-64; P < 0.001). There were 15 nulliparas in group B.
      Nine women in group A had an internal anterior rectal wall procidentia, and one
      woman had an external anterior rectal wall procidentia. In group A, the
      rectovaginal pouch was significantly deeper, the sigmoid mesocolon at S1 shorter
      and showed more often a straight course (P < 0.05). These characteristics (termed
      "grande fosse pelvienne") were present in 23 women (64%) in group A and in 6
      (14%) in group B, three of the latter were young nulliparas (P < 0.001). Age,
      parity, menopausal status, body mass index, constipation, and varicose veins were
      not associated with a grande fosse pelvienne. The typical anatomy in women with
      an enterocele and anterior rectal wall procidentia was a sigmoid colon with a
      straight course and a short mesentery at S1 and a rectovaginal pouch that covered
      more than half of the vaginal length. It may be a congenital condition and
      important in the development of an enterocele and rectal wall procidentia.

PMID- 16287127
TI  - Novel statistical-thermodynamic methods to predict protein-ligand binding
      positions using probability distribution functions.
AB  - We present two novel methods to predict native protein-ligand binding positions.
      Both methods identify the native binding position as the most probable position
      corresponding to a maximum of a probability distribution function (PDF) of
      possible binding positions in a protein active site. Possible binding positions
      are the origins of clusters composed, on the basis of root-mean square deviations
      (RMSD), from the multiple ligand positions determined by a docking algorithm. The
      difference between the methods lies in the ways the PDF is derived. To validate
      the suggested methods, we compare the averaged RMSD of the predicted ligand
      docked positions relative to the experimentally determined positions for a set of
      135 PDB protein-ligand complexes. We demonstrate that the suggested methods
      improve docking accuracy by as much as 21-24% in comparison with a method that
      simply identifies the binding position as the energy top-scored ligand position.

PMID- 16287130
TI  - Demography, range use, and behavior in black lemurs (Eulemur macaco macaco) at
      Ampasikely, northwest Madagascar.
AB  - We studied a black lemur population over a 2-year period (1992-1993) and 8 years
      later (2000) in a 50-ha secondary forest in northwest Madagascar. All of the
      animals were marked to investigate population dynamics and seasonal variation in
      ranging and behavior, and new data on black lemurs were obtained. Our data on
      demographic characteristics were expanded to include other forest sites and
      contrasted with those collected in other Eulemur macaco macaco field studies, in
      relation to human activity and the presence of introduced and cultivated plant
      species. Density is affected by deforestation and hunting. Group size and home
      range depend on the composition of the forest and probably food patches. Sex
      ratio at birth varies according to the number of females per group, a result that
      fits the local resource competition model. Groups are multimale-multifemale, and
      adult females form the core of the groups. Reproductive parameters indicate
      sharply defined seasonal breeding, a high female reproductive rate, and birth
      synchrony. Changes in group composition reveal male and female juvenile
      dispersal, male transfer between groups at the time of mating, and adult female
      transfer and group fission when groups exceed a critical size. At mating and
      birth, intergroup agonistic encounters occurred at home-range boundaries, and
      larger groups were dominant over smaller groups. Patterns of intragroup
      interactions suggest that males compete for access to groups of females during
      the mating season, and that females may compete for food resources during the
      birth season. Our study also reports female social dominance and lack of sexual
      weight dimorphism in this species.

PMID- 16287128
TI  - Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain
      and prevent secretion of mutant matrilin-3.
AB  - Multiple epiphyseal dysplasia (MED) is a relatively common skeletal dysplasia
      that can present in childhood with a variable phenotype of short stature and pain
      and stiffness in the large joints, and often progresses to early-onset
      osteoarthritis in adulthood. Mutations in the matrilin-3 gene (MATN3) have
      recently been shown to underlie some forms of autosomal dominant MED. To date all
      MED mutations in matrilin-3 cluster in the single A-domain, suggesting that they
      may disrupt the structure and/or function of this important domain. To determine
      the effects of MATN3 mutations on the structure and function of matrilin-3 we
      expressed both normal and mutant matrilin-3 in mammalian cells. Wild-type (wt)
      matrilin-3 was efficiently secreted into conditioned medium, whereas mutant
      matrilin-3 was retained and accumulated within the cell. Furthermore, when the
      mutant A-domains were examined individually, they existed primarily in an
      unfolded conformation. Co-immunoprecipitation experiments demonstrated that the
      mutant A-domains were specifically associated with ERp72, a chaperone protein
      known to be involved in mediating disulfide bond formation. Light microscopy of
      cartilage from an MED patient with a MATN3 mutation showed the presence of
      intracellular material within the chondrocytes, whilst the overall matrix
      appeared normal. On electron micrographs, the inclusions noted at the light
      microscopy level appeared to be dilated cisternae of rough endoplasmic reticulum
      and immunohistochemical analysis confirmed that the retained protein was matrilin
      3. In summary, the data presented in this paper suggest that MED caused by MATN3
      mutations is the result of an intracellular retention of the mutant protein.

PMID- 16287131
TI  - Plasma cell granuloma of the mediastinum with secondary renal amyloidosis.

PMID- 16287129
TI  - Crystal structure of virulence factor CJ0248 from Campylobacter jejuni at 2.25 A
      resolution reveals a new fold.

PMID- 16287133
TI  - Does cognitive function influence alaryngeal speech rehabilitation?
AB  - BACKGROUND: We sought to define the cognitive domains that influence valved
      speech rehabilitation. METHODS: Sixteen laryngectomees with primary
      tracheoesophageal punctures were randomly recruited from one head and neck unit.
      They were assessed by a consultant neuropsychologist and a speech therapist.
      Speech therapy time was determined from speech therapy notes. RESULTS: The Digit
      Symbol Substitution Test, assessing learning speed and processing speed,
      correlated significantly with speech therapy time in the first (p = .002) and
      third (p = .014) postoperative years, respectively. Categorical fluency
      assessment correlated positively with speech therapy time in the first year (p =
      .009). Learning speed (p = .007) and categorical fluency (p = .041) correlated
      positively with the fall in speech therapy input between the first and third year
      after laryngectomy. CONCLUSIONS: Learning speed, processing speed, and
      categorical fluency strongly influence alaryngeal speech rehabilitation. This
      study highlights the potential for pre-laryngectomy cognitive assessment to help
      plan alaryngeal speech rehabilitation. This has significant resource
      implications.

PMID- 16287134
TI  - Osteomyocutaneous peroneal artery perforator flap for reconstruction of composite
      maxillary defects.
AB  - BACKGROUND: Composite maxillary defects often involve the maxilla, nasal mucosa,
      palate, and maxillary sinus. We presented the surgical techniques and outcome of
      the osteomyocutaneous peroneal artery perforator (PAP) flap for reconstruction of
      composite maxillary defects. METHODS: Six patients underwent an osteomyocutaneous
      PAP flap reconstruction of composite maxillary defects. The average age was 52
      years. The defects were Cordeiro type II in three patients and type IV midfacial
      defects in another three patients. RESULTS: No total or partial flap failures
      occurred. At a mean 12-month follow-up, five patients had a normal speech and
      were able to eat a regular diet. One patient tolerated a soft diet and had
      intelligible speech. One patient had ectropion develop. Excellent cosmesis was
      found in five patients. CONCLUSIONS: The osteomyocutaneous PAP flap represents a
      further refinement of the fibula flap and increases its versatility, with
      multiple skin paddles, bone segments, and soleus muscle independently isolated.
      It is a comparable reconstruction option for composite maxillary defects.

PMID- 16287132
TI  - Impact of nutrition support on treatment outcome in patients with locally
      advanced head and neck squamous cell cancer treated with definitive radiotherapy:
      a secondary analysis of RTOG trial 90-03.
AB  - BACKGROUND: The aim was to evaluate the relationship between nutrition support
      (NS) on host toxicity and cancer outcome in patients with locally advanced head
      and neck squamous cell carcinoma (HNSCC) undergoing definitive radiotherapy
      (XRT). METHODS: We performed a secondary analysis of Radiation Therapy Oncology
      Group (RTOG) 90-03, a prospective randomized trial evaluating four definitive XRT
      fractionation schedules in patients with locally advanced HNSCC, which
      prospectively collected data on NS delivered before treatment (BNS), during
      treatment (TNS), and after definitive XRT. NS data and pretreatment
      characteristics of the 1073 evaluable patients were analyzed against therapy
      toxicity and outcome. RESULTS: Patients receiving BNS experienced significantly
      less weight loss by the end of treatment and less grade 3 to 4 mucositis than
      patients not receiving BNS. However, patients receiving BNS had a poorer 5-year
      actuarial locoregional control rate than patients receiving TNS or no NS (29%,
      55%, and 57%, respectively, p < .0001) and a poorer 5-year overall survival rate
      (16%, 36%, and 49%, respectively, p < .0001). Patients receiving BNS were
      significantly more likely to have a higher T classification, N status, and
      overall American Joint Committee on Cancer (AJCC) stage and initial presentation
      with greater pretreatment weight loss, and a poorer Karnofsky Performance Status
      (KPS) than patients not receiving BNS. After adjusting for the impact of these
      prognostic factors through a recursive partition analysis, a multivariate
      analysis with a stratified Cox model found that BNS was still a highly
      significant independent prognostic factor for increased locoregional failure
      (hazards ratio [HR], 1.47; 95% confidence interval [CI], 1.21-1.79; p < .0001)
      and death (HR, 1.41; 95% CI, 1.19-1.67; p < .0001). CONCLUSION: In this study,
      the largest prospective evaluation of nutrition data in treated patients with
      cancer, BNS was associated with inferior treatment outcome in the patients with
      HNSCC undergoing XRT. These results should be considered hypothesis generating
      and encourage prospective clinical research and identification of the mechanisms
      underlying this finding.

PMID- 16287136
TI  - Health-related quality of life in patients with pharyngeal carcinoma: a five-year
      follow-up.
AB  - PURPOSE: The purpose was to evaluate the health-related quality of life (HRQL) of
      patients with pharyngeal carcinoma at diagnosis and after 1 and 5 years in
      relation to tumor location and treatment modality in a prospective multicenter
      study. METHODS: Eighty-nine patients with pharyngeal carcinoma (mean age, 60.0
      years; 76% men) were evaluated using the European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and the
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire Head and Neck Cancer Module (EORTC QLQ-H&N35). RESULTS: Problems
      with dry mouth and teeth became worse between diagnosis and the 5-year follow-up.
      Problems with thick secretions and teeth increased between 1 and 5 years. The
      HRQL at diagnosis was associated with survival. Patients with oropharyngeal
      carcinoma reported better HRQL than patients with hypopharyngeal carcinoma.
      CONCLUSIONS: For patients with pharyngeal carcinoma, the HRQL at diagnosis seems
      to be an important factor for the prognosis of both HRQL over time and survival.
      Treatment of pharyngeal carcinoma often results in long-term side effects such as
      dry mouth, problems with teeth, and thick secretions.

PMID- 16287135
TI  - Stereotactic radiosurgery plus intracavitary irradiation in the salvage of
      nasopharyngeal carcinoma.
AB  - BACKGROUND: We sought to assess the efficacy and complications of linear
      accelerator-based stereotactic radiosurgery (SRS) plus intracavitary irradiation
      (ICI) as salvage treatment for local persistent and recurrent nasopharyngeal
      carcinoma (NPC) after primary external beam radiotherapy (EBRT). METHODS: Between
      July 1995 and June 2003, 36 patients (25 men and 11 women; median age, 48 years;
      range, 22-66 years) with local recurrent NPC confined to the nasopharynx (rT1) or
      limited extension to the parapharynx and nasal cavity (rT2) were treated with SRS
      plus ICI. Nineteen patients had rT1 and 17 had rT2 disease. Five patients (13.8%)
      had persistent disease, and 31 patients (86.1%) had recurrent disease using the
      definition of >4 months after the primary treatment as recurrent relapse. The
      median target volume was 36.3 cm(3) (range, 10.3-56.2 cm(3)) for the SRS
      treatment. All patients received 18 Gy to the 90% isodose line followed by two
      separate ICI 6 Gy each to 0.5 cm from the surface of the endotracheal balloon.
      Patients were assessed with serial nasoendoscopy and repeat scans (CT or MRI) at
      3 months, and suspicious lesions were rebiopsied. RESULTS: The median follow-up
      for surviving patients was 4.24 years (range, 0.73-8.81 years). Twenty-two of 36
      (61%) patients were alive at the time of reporting. Twenty patients were free of
      disease, and two patients were alive with disease. Fourteen of 36 (39%) patients
      had died (five of distant metastases, six of local recurrences, two of both local
      disease and distant metastases, and one of unrelated cause). Patients with rT1
      disease (median survival not reached) fared better that patients with rT2 disease
      (median survival, 4.6 years). The actuarial 5-year disease-free survival and
      overall survival (OS) were 57% (rT1 78%, rT2 39%) and 62% (rT1 80%, rT2 48%),
      respectively. The actuarial 5-year local control was 65% (rT1 82%, rT2 49%). The
      treatment was well tolerated with no significant acute complications. Sixteen
      patients (44%) had late complications, including palatal fibrosis in six patients
      (17%), trismus in seven patients (20%), cranial nerve palsies in seven patients
      (20%), temporal lobe necrosis in two patients (8%), and osteoradionecrosis of the
      skull base in six patients (17%). The complication-free survival rates at 2 and 5
      years were 70% (95% confidence interval [CI], 56% to 87%) and 31% (95% CI, 17% to
      56%), respectively. No patient died as a direct result of the late complication.
      CONCLUSION: Although our series is small, the combination of SRS and ICI seems to
      be an effective salvage treatment for early-stage recurrent NPC. The OS of 62% at
      5 years is very encouraging and favorable compared with reported reirradiation or
      surgical series. The late complications are considerable but expected because of
      the high doses of radiation previously delivered. The ideal dose fractionation
      for SRS and ICI is unknown and remains to be defined.

PMID- 16287137
TI  - Risk of malignancy in Filipinos with thyroid nodules--a matched pair analysis.
AB  - BACKGROUND: Ethnicity is an infrequently cited risk factor for thyroid cancer.
      This study aims to determine whether patients of Filipino origin assessed at a
      tertiary referral center are at increased risk of thyroid cancer and to quantify
      that risk. METHODS: This is a retrospective analysis of 72 Filipino patients with
      thyroid nodules undergoing thyroidectomy individually matched to 72 controls
      according to demographics, risk factors, and pre-referral investigations.
      RESULTS: Thyroid cancer was found in 50 (69.4%) Filipino patients compared with
      28 (38.9%) controls. Odds ratio for malignancy in Filipinos was 3.57 (95%
      confidence interval, 1.79-7.12). Pathologic characteristics of thyroid cancer
      were not significantly different in the two groups. The median follow-up for
      Filipino patients was 14.1 months (range, 1.4 months-19.7 years). Recurrence
      occurred in four Filipino patients, and one patient with anaplastic thyroid
      cancer died of the disease. CONCLUSIONS: Filipino patients with thyroid nodules
      are at significantly increased risk of thyroid cancer compared with matched
      controls, and hence the index of suspicion for malignancy should be high when
      evaluating these patients.

PMID- 16287138
TI  - Cancer recurrence after total laryngectomy: treatment options, survival, and
      complications.
AB  - BACKGROUND: A follow-up schedule to detect asymptomatic cancer recurrence is
      offered to all patients with laryngeal cancer. In this study, the therapeutic
      options, prognosis, and morbidity of patients with total laryngectomy, who were
      found to have cancer recurrence during this follow-up schedule were determined.
      METHODS: Patients who had undergone a total laryngectomy between January 1, 1990,
      and January 1, 2000, and had cancer recurrence were included. Data from this
      group were analyzed retrospectively. RESULTS: The prognosis was poor after the
      development of cancer recurrence. Curative therapy could only be offered to 27.5%
      of these patients. Only 5% of the patients were disease free at the end of the
      study period. Many patients with cancer recurrence needed interventions. A large
      proportion of them had complications. CONCLUSIONS: The follow-up schedule offered
      to patients after total laryngectomy should put greater emphasis on care than on
      early detection of cancer recurrence.

PMID- 16287139
TI  - Identification and functional analysis of CITED2 mutations in patients with
      congenital heart defects.
AB  - Recent reports have demonstrated that mice lacking the transcription factor
      Cited2 die in utero showing various cardiac malformations. We present for the
      first time functionally relevant mutations of CITED2 in patients with congenital
      heart defects (CHDs). CITED2 encodes a CREBBP/EP300 interacting transcriptional
      modulator of HIF1A and TFAP2. To study the potential impact of sequence
      variations in CITED2 for CHDs in humans, we screened a cohort of 392 well
      characterized patients and 192 control individuals using DHPLC, sequencing, and
      Amplifluor genotyping techniques. We identified 15 CITED2 nucleotide alterations.
      Seven of these alterations were found only in CHD patients and were not detected
      in controls, including three mutations leading to alterations of the amino acid
      sequence (p.Ser170_Gly178del, p.Gly178_Ser179ins9, and p.Ser198_Gly199del). All
      three of these amino acid changing mutations cluster in the serine-glycine-rich
      junction of the protein, to which no functionality had heretofore been assigned.
      Here we show that these mutations significantly reduce the capacity of CITED2 to
      transrepress HIF1A, and that the p.Ser170_Gly178del mutation significantly
      diminishes TFAP2C coactivation. This reveals a modifying role for the serine
      glycine-rich region in CITED2 function. In summary, the observation of these
      mutations in patients with septal defects indicates that CITED2 has a causative
      impact in the development of CHD in humans.

PMID- 16287140
TI  - B. subtilis ykuD protein at 2.0 A resolution: insights into the structure and
      function of a novel, ubiquitous family of bacterial enzymes.
AB  - The crystal structure of the product of the Bacillus subtilis ykuD gene was
      solved by the multiwavelength anomalous dispersion (MAD) method and refined using
      data to 2.0 A resolution. The ykuD protein is a representative of a distinctly
      prokaryotic and ubiquitous family found among both pathogenic and nonpathogenic
      Gram-positive and Gram-negative bacteria. The deduced amino acid sequence reveals
      the presence of an N-terminal LysM domain, which occurs among enzymes involved in
      cell wall metabolism, and a novel, putative catalytic domain with a highly
      conserved His/Cys-containing motif of hitherto unknown structure. As the wild
      type protein did not crystallize, a double mutant was designed
      (Lys117Ala/Gln118Ala) to reduce excess surface conformational entropy. As
      expected, the structure of the LysM domain is similar to the NMR structure
      reported for an analogous domain from Escherichia coli murein transglycosylase
      MltD. The molecular model also shows that the 112-residue-long C-terminal domain
      has a novel tertiary fold consisting of a beta-sandwich with two mixed sheets,
      one containing five strands and the other, six strands. The two beta-sheets form
      a cradle capped by an alpha-helix. This domain contains a putative catalytic site
      with a tetrad of invariant His123, Gly124, Cys139, and Arg141. The
      stereochemistry of this active site shows similarities to peptidotransferases and
      sortases, and suggests that the enzymes of the ykuD family may play an important
      role in cell wall biology.

PMID- 16287141
TI  - Younger birth cohort correlates with higher breast and ovarian cancer risk in
      European BRCA1 mutation carriers.
AB  - Mutations in the BRCA1 gene result in an elevated risk of breast cancer (BC) and
      ovarian cancer (OC). However, risk estimates vary depending on the study
      population and statistical methodology used, and there are indications that the
      birth cohort and location of the mutation influence cancer risk. We investigated
      the risks for BC and OC associated with BRCA1 mutations in a young cohort of
      female mutation carriers who were identified by molecular genetic testing and
      belonged to a genetically heterogeneous Central European population. The study
      included 106 healthy and 158 affected carriers identified at an Austrian risk
      evaluation center. Risk estimation employed the product limit method. The log
      rank test was used to compare different strata. The risk of developing cancer to
      age 70 was found to be 85% for BC (95% CI 75-97%) and 53% for OC (95% CI 37-68%).
      Female mutation carriers born in 1958 or later were subject to a significantly
      higher risk of BC (P=0.005; 27% vs. 46% to age 40) and OC (P=0.006; 2% vs. 8% to
      age 40) than those born earlier. Mutations in exon 11 were associated with lower
      BC risk than mutations in exons 1-10 (P=0.008) and exons 12-24 (P=0.0006). OC
      risk was not influenced by mutation location (P=0.86). We conclude that female
      BRCA1 mutation carriers should be counseled about their cohort-dependent cancer
      risk. Further research into variables that affect cancer risk and are amenable to
      modification (e.g., lifestyle-related factors) should be considered a priority.

PMID- 16287143
TI  - Four novel TMC1 (DFNB7/DFNB11) mutations in Turkish patients with congenital
      autosomal recessive nonsyndromic hearing loss.
AB  - Mutations in the transmembrane channel-like gene 1 (TMC1) cause prelingual
      autosomal recessive (DFNB7/11) and postlingual progressive autosomal dominant
      (DFNA36) nonsyndromic hearing loss. To determine the genetic causes of autosomal
      recessive nonsyndromic hearing loss (ARNSHL) in the northeast and east of Turkey,
      65 unrelated families without mutations in the protein coding region of the GJB2
      (GJB2-negative) were analyzed. A genomewide scan for homozygosity and linkage
      analysis in one of these families revealed a 13.2 cM critical region between
      D9S273 and D9S153 at chromosome 9p13.2-q21.31 with a maximum two-point lod score
      of 4.00 at theta=0.0 for marker D9S175. TMC1 is in this critical region.
      Homozygosity screening with intragenic markers for TMC1 in the remaining 64
      families suggested involvement of this gene in three additional families.
      Subsequent sequencing of TMC1 in these four families revealed four novel
      homozygous mutations, c.776A>G [p.Tyr259Cys], c.821C>T [p.Pro274Leu], c.1334G>A
      [p.Arg445His], and c.1083_1087delCAGAT [p.Arg362ProfrX6]. Our results indicate
      that TMC1 mutations account for at least 6% (4/65) of ARNSHL in GJB2-negative
      Turkish families from the northeast and east of Turkey.

PMID- 16287142
TI  - Identification of genetic aberrations on chromosome 22 outside the NF2 locus in
      schwannomatosis and neurofibromatosis type 2.
AB  - Schwannomatosis is characterized by multiple peripheral and cranial nerve
      schwannomas that occur in the absence of bilateral 8th cranial nerve schwannomas.
      The latter is the main diagnostic criterion of neurofibromatosis type 2 (NF2),
      which is a related but distinct disorder. The genetic factors underlying the
      differences between schwannomatosis and NF2 are poorly understood, although
      available evidence implicates chromosome 22 as the primary location of the
      gene(s) of interest. To investigate this, we comprehensively profiled the DNA
      copy number in samples from sporadic and familial schwannomatosis, NF2, and a
      large cohort of normal controls. Using a tiling-path chromosome 22 genomic array,
      we identified two candidate regions of copy number variation, which were further
      characterized by a PCR-based array with higher resolution. The latter approach
      allows the detection of minute alterations in total genomic DNA, with as little
      as 1.5 kb per measurement point of nonredundant sequence on the array. In DNA
      derived from peripheral blood from a schwannomatosis patient and a sporadic
      schwannoma sample, we detected rearrangements of the immunoglobulin lambda (IGL)
      locus, which is unlikely to be due to a B-cell specific somatic recombination of
      IGL. Analysis of normal controls indicated that these IGL rearrangements were
      restricted to schwannomatosis/schwannoma samples. In the second candidate region
      spanning GSTT1 and CABIN1 genes, we observed a frequent copy number polymorphism
      at the GSTT1 locus. We further describe missense mutations in the CABIN1 gene
      that are specific to samples from schwannomatosis and NF2 and make this gene a
      plausible candidate for contributing to the pathogenesis of these disorders.

PMID- 16287144
TI  - The frequency of mucolipidosis type IV in the Ashkenazi Jewish population and the
      identification of 3 novel MCOLN1 mutations.
AB  - Mucolipidosis type IV (MLIV) is a neurodegenerative lysosomal storage disorder
      that occurs in an increased frequency in the Ashkenazi Jewish (AJ) population.
      The frequency of the disease in this population has been established by the
      testing of 66,749 AJ subjects in the Dor Yeshorim program, a unique premarital
      population-screening program designed for the Orthodox Jewish community. A
      carrier rate of 0.0104 (95% C.I 0.0097-0.011) was found. The distribution of the
      2 AJ founder mutations, namely, c.416-2A>G and c.1_788del, was determined to be
      78.15% and 21.85%, respectively. Three novel mutations were identified in non
      Jewish MLIV patients, a missense mutation c.1207C>T, p.Arg403Cys; a 2bp deletion,
      c.302_303delTC; and a nonsense, c.235C>T, Gln79X.

PMID- 16287148
TI  - Self-criticism and depressive symptomatology interact to predict middle school
      academic achievement.
AB  - Although previous research has implicated adolescent depression in academic
      difficulties, few studies have explored the role of cognitive/personality factors
      in this area. To address this gap, the present study examines the role of self
      criticism in academic functioning among early adolescent students over a 1-year
      interval. We hypothesized and found that adolescent self-criticism and depressive
      symptomatology interacted to predict decreased grade point average (GPA) over
      time, an interaction that was found predominantly in boys. This finding
      illustrates the need to integrate research on personality and psychopathology
      into educational psychology.

PMID- 16287149
TI  - Meta-analysis of the factor structures of four depression questionnaires: Beck,
      CES-D, Hamilton, and Zung.
AB  - Four separate metaanalyses of factor analyses were conducted for the Beck
      Depression Inventory (BDI), the Center for Epidemiological Studies Depression
      Scale (CES-D), the Hamilton Rating Scale for Depression (HRSD), and the Zung Self
      Rating Depression Scale (SDS). The total number of participants (N) and studies
      (k) included in each of the metaanalyses were the following: BDI (N = 13,643, k =
      33), CES-D (N = 22,340, k = 28), HRSD (N = 2,606, k = 17), and SDS (N = 12,621, k
      = 13). Metaanalysis results suggest that the specific depression symptom factors
      within each test appear to be relatively robust and well established and match
      fairly closely previously hypothesized factor structures. A general Depression
      Severity factor and a small Somatic Symptoms factor are found in all four tests
      and two tests had a small Positive Affect factor. There were fewer common
      specific depression symptom factors across tests than expected.

PMID- 16287150
TI  - Treatment motives as predictors of acquisition and transfer of relaxation methods
      to everyday life.
AB  - This article presents results from four studies of the significance of type and
      number of initial treatment motives for acquisition and transfer to everyday life
      of progressive relaxation (PR) and autogenic training (AT). On the basis of
      theories of treatment motivation and compliance, we hypothesize that motives for
      participation are determinants of learning and transfer. Results are reported
      from (1) two studies with 113 participants in introductory courses on AT and 94
      participants in introductory courses on PR and (2) two replication studies with
      94 (AT) and 101 participants (PR). Participants indicated their motives for
      participation. Short-term indicators of treatment success include number of
      dropouts and subjective evaluations of relaxation exercises; long-term outcomes
      include transfer of relaxation exercises to everyday life and evaluations of
      exercise evaluations at follow-up 3 to 6 months after the end of course. Results
      suggest that for both AT and PR, dropout and subjective relaxation exercise
      evaluations can be predicted from participation motives. Long-term outcomes can
      be predicted only for AT. However, for both PR and AT it is shown that for up to
      four motives, the number of initial course motives is correlated with short-term
      and long-term predictors of course outcome. We conclude that motivation for
      participation is highly relevant to client-course matching and adaptive
      indication of relaxation therapies. Results lead to a threshold hypothesis about
      the relationship between the number of participation motives and short-term as
      well as long-term learning and transfer outcome.

PMID- 16287151
TI  - Personality traits as risk factors of depression and anxiety among Japanese
      students.
AB  - The aim of this study is to examine the effects of personality (temperament and
      character) on specific depression and specific anxiety. A total of 541 Japanese
      undergraduates were investigated by using the Temperament and Character Inventory
      (TCI) and the Hospital Anxiety and Depression (HAD) scale. Hierarchical multiple
      regression analyses demonstrated that specific depression was predicted by lower
      Reward-Dependence, Persistence, Self-Directedness, Cooperativeness, and Self
      Transcendence; specific anxiety was predicted by higher Novelty-Seeking, Harm
      Avoidance, Persistence, and Self-Transcendence, and lower Self-Directedness.
      Immaturity of Self-Directedness is a risk factor for negative affectivity.
      Immaturity of all character dimensions is a risk factor for specific depression.
      The relationship between Harm-Avoidance and depression in previous studies may be
      linked partly to somatic symptoms that were deliberately eliminated in the HAD
      scale.

PMID- 16287152
TI  - Pancreatic juice cytology in the diagnosis of intraductal papillary mucinous
      neoplasm of the pancreas: significance of sampling by peroral pancreatoscopy.
AB  - BACKGROUND: The examination of pancreatic juice cytology could hypothetically
      contribute to the establishment of a definite diagnosis of malignant intraductal
      papillary mucinous neoplasm of the pancreas (IPMN), but to the authors'
      knowledge, its significance has not been confirmed to date. The current study was
      conducted to assess the diagnostic value of pancreatic juice cytology in IPMN and
      to examine the usefulness of peroral pancreatoscopy (POPS) in sampling pancreatic
      juice. METHODS: The study subjects were comprised of 103 patients with IPMN who
      underwent surgical resection of pancreatic tumors (adenoma in 29 patients,
      borderline in 17 patients, carcinoma in situ in 25 patients, and invasive
      carcinoma in 32 patients). Pancreatic juice was collected with a catheter in 71
      patients and by POPS in 32 patients. Patients with pancreatic carcinoma (n = 81)
      and chronic pancreatitis (n = 76) also were investigated. RESULTS: The cytologic
      diagnosis was found to be of nondiagnostic value in only one patient with an
      IPMN, whereas it was of no diagnostic value in 14 of the patients with pancreatic
      carcinoma (17.3%), a difference that was statically significant (P < 0.001). The
      location of the IPMN (either in the pancreas or the pancreatic ducts) was not
      found to significantly affect the diagnostic value of the test. The sensitivity
      for IPMN was 62.2% when pancreatic juice was collected by POPS, and was 38.2%
      when it was collected using a catheter. In the case of pancreatic carcinoma, the
      sensitivity of pancreatic juice cytology was found to be 25.4%, which was
      significantly lower than that for IPMN when the pancreatic juice was collected by
      POPS (P < 0.001). CONCLUSIONS: Pancreatic juice cytology was found to have better
      diagnostic value in the patients with IPMNs compared with those with pancreatic
      carcinoma. POPS was found to be useful for the collection of pancreatic juice.

PMID- 16287153
TI  - Risk factors for variant Creutzfeldt-Jakob disease: a case-control study.
AB  - OBJECTIVE: To investigate the potential risk factors for variant Creutzfeldt
      Jakob disease (VCJD) in the United Kingdom. METHODS: Definite and probable vCJD
      cases (n = 136) were residing in Great Britain at disease onset, and were
      referred between May 1995 and November 2003. Control subjects (n = 922) were
      recruited between 2002 and 2003, from 100 randomly selected geographical clusters
      sampled to represent the geographical distribution of vCJD. RESULTS: Reported
      frequent consumption of beef and beef products thought likely to contain
      mechanically recovered or head meat, or both, including burgers and meat pies,
      was associated with increased risk for vCJD, as was reported frequent chicken
      consumption. Surgical operations were generally similarly reported for cases and
      control subjects, with the exception of a small group of minor operations,
      possibly attributable to underreporting in control subjects. Cases and control
      subjects had similar reported occupational histories and exposure to animals.
      INTERPRETATION: These findings are consistent with dietary exposure to
      contaminated beef products being the main route of infection of vCJD, but recall
      bias cannot be excluded. There was no convincing evidence of increased risk
      through medical, surgical, or occupational exposure or exposure to animals.

PMID- 16287154
TI  - Splice-site contribution in alternative splicing of PLP1 and DM20: molecular
      studies in oligodendrocytes.
AB  - Mutations in the proteolipid protein 1 (PLP1) gene cause the X-linked
      dysmyelinating diseases Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia
      2 (SPG2). We examined the severity of the following mutations that were suspected
      of affecting levels of PLP1 and DM20 RNA, the alternatively spliced products of
      PLP1: c.453G>A, c.453G>T, c.453G>C, c.453+2T>C, c.453+4A>G, c.347C>A, and
      c.453+28_+46del (the old nomenclature did not include the methionine codon:
      G450A, G450T, G450C, IVS3+2T>C, IVS3+4A>G, C344A, and IVS3+28-+46del). These
      mutations were evaluated by information theory-based analysis and compared with
      mRNA expression of the alternatively spliced products. The results are discussed
      relative to the clinical severity of disease. We conclude that the observed PLP1
      and DM20 splicing patterns correlated well with predictions of information theory
      based analysis, and that the relative strength of the PLP1 and DM20 donor splice
      sites plays an important role in PLP1 alternative splicing.

PMID- 16287155
TI  - Germline mutations of the MSR1 gene in prostate cancer families from Germany.
AB  - The MSR1 gene at 8p22 has been suggested as a candidate gene for hereditary
      prostate cancer because germline variants have been found to be associated with
      the disease. Aside from a single nonsense mutation (R293X) that was found
      repeatedly at low frequencies in several samples, little evidence has been gained
      by follow-up studies to confirm the gene's relevance for prostate cancer.
      Prompted by reasonable support for a linkage to 8p22, we sought to determine the
      mutation spectrum of MSR1 in our family sample. Screening of 139 probands
      (representing 139 prostate cancer families) revealed 15 novel and a total of 20
      sequence variants within the 10 coding exons and their intronic proximities.
      Aside from the known mutation c.877C>T (R293X) present in two of our families, we
      identified a second nonsense allele (c.251C>G; S84X) and a splice-site mutation
      (c.818-1G>A) that results in mRNA instability (each in a single pedigree). The
      novel missense alleles were c.703C>T (H235Y), c.856C>T (P286S), c.905C>T (P302L),
      c.1193C>G (A398G), and c.1289A>G (K430R). Of the eight variants that affect the
      encoded protein (splice site, nonsense, and missense), only R293X as well as the
      polymorphism c.823C>G (P275A) were additionally present at remarkable frequencies
      in further samples of sporadic prostate cancer and controls. Of note, carriers of
      R293X were equally frequent in 367 sporadic prostate cancer cases (1.9%) and in
      197 controls (2.0%). To our knowledge, our study is the first to demonstrate
      further loss of function variants of MSR1 apart from R293X. Nevertheless, the low
      frequencies of deleterious alleles, in addition to an apparently moderate
      penetrance, does not support MSR1 as a major susceptibility gene in this family
      sample.

PMID- 16287156
TI  - Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 are associated
      with susceptibility to lung cancer.
AB  - The tumor suppressor TP53 pathway plays a crucial role in preventing
      carcinogenesis through its ability to impose cell cycle arrest and apoptosis
      following DNA damage and oncogene activation. MDM2 is a key negative regulator of
      the TP53 pathway and is overexpressed in many cancers as oncoprotein. We
      investigated the association between genetic variation in the promoter region of
      MDM2 (c.-5+309G>T, rs2279744:g.G>T) and the coding region of TP53 (c.215G>C,
      rs1042522:g.G>C, designated Arg72Pro) and the risk of developing lung cancer. The
      genotypes of 1,106 patients and 1,420 controls were determined by tetra-primer
      amplification refractory mutation system (ARMS)-PCR or PCR-based restriction
      fragment length polymorphism (RFLP). Associations with risk of lung cancer were
      estimated by logistic regression. We observed an increased lung cancer risk
      associated with the MDM2 GG (odds ratio [OR] = 1.83, 95% confidence interval [CI]
      = 1.45-2.32) and TG (OR = 1.33, 95% CI = 1.09-1.63) genotypes. An increased risk
      was also associated with the TP53 Pro/Pro genotype (OR = 1.47, 95% CI = 1.17
      1.85, P = 0.003) compared to the Arg/Arg genotype. The gene-gene interaction of
      MDM2 and TP53 polymorphisms increased lung cancer risk in a supermultiplicative
      manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 4.56,
      95% CI = 2.76-7.54). Significant interactions were observed between these
      polymorphisms (respectively and jointly) and smoking (OR = 10.41, 95% CI = 5.26
      20.58) for smokers with both the MDM2 GG and TP53 Pro/Pro genotypes. In
      conclusion, genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53
      contribute to the risk of developing lung cancer.

PMID- 16287158
TI  - Three-dimensional anatomy of the conduction system of the early embryonic rabbit
      heart.
AB  - The complete embryonic cardiac conduction system is difficult to view in three
      dimensions, primarily because there has not been a marker of all segments of the
      normal system throughout all stages of development. Imaging of the conduction
      system components within the atria has been particularly controversial because
      different markers reveal different pathways that may or may not represent
      conduction system components. The conduction system of the adult and embryonic
      rabbit, however, can be labeled in its entirety with the neurofilament marker, NF
      160. The conduction system of rabbit embryos at several stages of development
      spanning cardiac septation was therefore investigated. Optical mapping of the
      electrical signature of the conduction system previously revealed a close
      correlation between the cardiac activation patterns and the anatomy as shown by
      serial sections. The 3D relationship between the components of the conduction
      system could only be inferred from the 2D sections. The sections were
      consequently reconstructed using a commercial software program (AutoQuant). This
      is the first demonstration of the three-dimensional complete normal rabbit
      embryonic cardiac conduction system at several stages of development.

PMID- 16287159
TI  - Human Proteome Organisation Proteomics Standards Initiative. Pre-Congress
      Initiative.
AB  - The plenary session of the Proteomics Standards Initiative of the Human Proteome
      Organisation discussed the current status of the ongoing work in the fields of
      molecular interactions, mass spectrometry and the description of protein
      modifications. In addition, new areas are being opened up, in particular
      developing standards for the description and exchange of data from gel
      electrophoresis experiments. The General Proteomics Standards group is now
      working closely with the Functional Genomics Experiment efforts to define a
      general standard in which to encode data that will enable a systems biology
      approach to data analysis.

PMID- 16287160
TI  - Phase-transfer-catalyzed asymmetric aza-Henry reaction using N-carbamoyl imines
      generated in situ from alpha-amido sulfones.

PMID- 16287161
TI  - C-C bond activation by octacarbonyldicobalt: [3+1] cocyclizations of
      methylenecyclopropanes with carbon monoxide.

PMID- 16287162
TI  - Phenol Ugi-smiles systems: strategies for the multicomponent N-arylation of
      primary amines with isocyanides, aldehydes, and phenols.

PMID- 16287163
TI  - Gelation of helical polypeptide-random coil diblock copolymers by a nanoribbon
      mechanism.

PMID- 16287164
TI  - Covalent functionalization: towards soluble multiwalled boron nitride nanotubes.

PMID- 16287165
TI  - Proteomic characterization of the cytotoxic mechanism of gold (III) porphyrin 1a,
      a potential anticancer drug.
AB  - There has been increasing interest in the potential applications of gold (III)
      complexes as anticancer drugs with higher cytotoxicity and fewer side effects
      than existing metal anticancer drugs. Our previous findings demonstrated that
      gold (III) porphyrin 1a preferentially induced apoptosis in a cancer cell line
      (SUNE1). In this study, we identified differentially expressed proteins related
      to the drug's cytotoxic action by comparing the protein alterations induced by
      gold (III) porphyrin 1a and cisplatin treatments. Several clusters of altered
      proteins were identified, including cellular structure and stress-related
      chaperone proteins, proteins involved in reactive oxygen species and enzyme
      proteins, translation factors, proteins that mediate cell proliferation or
      differentiation, and proteins participating in the internal degradation systems.
      Our results indicated that multiple factors leading to apoptosis were involved in
      drug cytotoxicity in SUNE1 cells. The balance between pro-apoptotic and anti
      apoptotic signals determined the final fate of cancer cells.

PMID- 16287166
TI  - Proteomic analysis of the Gallus gallus embryo at stage-29 of development.
AB  - The chicken (Gallus gallus) is one of the primary models for embryological and
      developmental studies. In order to begin to understand the molecular mechanisms
      underlying the normal and abnormal development of the chicken, we used 2-DE to
      construct a whole-embryo proteome map. Proteins were separated by IEF on IPG
      strips, and by 11% SDS-PAGE) gels. Protein identification was performed by means
      of PMF with MALDI-TOF-MS. In all, 105 protein spots were identified, 35 of them
      implicated in embryo development, 10 related with some diseases, and 16, finally,
      being proteins that have never been identified, purified or characterized in the
      chicken before. This map will be updated continuously and will serve as a
      reference database for investigators, studying changes at the protein level under
      different physiological conditions.

PMID- 16287167
TI  - Extending ribosomal protein identifications to unsequenced bacterial strains
      using matrix-assisted laser desorption/ionization mass spectrometry.
AB  - A protocol has been developed that allows protein identifications using available
      DNA-based or protein sequences from a reference strain of a bacterial species to
      be extended to bacterial strains for which no prior DNA-based or protein sequence
      information exists. The protocol is predicated on careful isolation of a specific
      sub-cellular group of proteins. In this study, ribosomal proteins were chosen due
      to their high relative abundance and similarity in copy number per cell. After
      isolation of ribosomal proteins, MALDI-MS is used to acquire accurate protein
      molecular weights. An iterative comparison of reference protein molecular weights
      and identities is made to the resulting data, allowing for the straightforward
      identification of ribosomal proteins from any non-reference strains. This
      approach can reveal differences between proteins at the amino acid or post
      translational level. The protocol was developed, validated and applied to
      ribosomal proteins from three strains of the extreme thermophile Thermus
      thermophilus. This approach revealed that nearly 60% of the ribosomal proteins
      from all three strains are identical. The extension of protein identification to
      additional bacterial strains can be useful in phylogenetic studies as well as in
      biomarker identification.

PMID- 16287168
TI  - Immobilization of diverse foreign proteins in viral polyhedra and potential
      application for protein microarrays.
AB  - Cypoviruses are insect viruses that produce a cytoplasmic crystalline particle
      called the polyhedron in which progeny virions are occluded. The virion
      structural protein, VP3, is implicated in the occlusion of viral particles into
      polyhedra. In this study, we determined the amino acid sequence of VP3 required
      for occlusion of viral particles into polyhedra and proposed that this sequence
      could be used as an immobilization signal to direct the stable incorporation of
      foreign proteins into polyhedra. A large-scale survey revealed that the
      immobilization signal could, in fact, direct the incorporation of a variety of
      human proteins into polyhedra. Immune reactivity and protein-protein interactions
      were detected on the surface of polyhedra containing immobilized foreign
      proteins, and these particles were shown to be highly stabilized against
      dehydration. We showed that these particles could be arrayed onto a glass slide
      by standard spotting and laser manipulation methods. Thus, this approach is well
      suited for protein expression, purification, and the development of protein
      microarrays.

PMID- 16287169
TI  - Arabidopsis cell wall proteome defined using multidimensional protein
      identification technology.
AB  - With the completion of the sequencing of the Arabidopsis genome and the recent
      advances in proteomic technology, the identification of proteins from highly
      complex mixtures is now possible. Rather than using gel electrophoresis and
      peptide mass fingerprinting, we have used multidimensional protein identification
      technology (MudPIT) to analyse the "tightly-bound" proteome for purified cell
      walls from Arabidopsis cell suspension cultures. Using bioinformatics for the
      prediction of signal peptides for targeting to the secretory pathway and for the
      absence of ER retention signal, 89 proteins were selected as potential
      extracellular proteins. Only 33% of these were identified in previous proteomic
      analyses of Arabidopsis cell walls. A functional classification revealed that a
      large proportion of the proteins were enzymes, notably carbohydrate active
      enzymes, peroxidases and proteases. Comparison of all the published proteomic
      analyses for the Arabidopsis cell wall identified 268 non-redundant genes
      encoding wall proteins. Sixty of these (22%) were derived from our analysis of
      tightly-bound wall proteins.

PMID- 16287170
TI  - Proteome analysis of chick embryonic cerebrospinal fluid.
AB  - During early stages of embryo development, the brain cavity is filled with
      embryonic cerebrospinal fluid (E-CSF), a complex fluid containing different
      protein fractions that contributes to the regulation of the survival,
      proliferation and neurogenesis of the neuroectodermal stem cells. Using 2-DE,
      protein sequencing and database searches, we identified and analyzed the proteome
      of the E-CSF from chick embryos (Gallus gallus). We identified 26 different gene
      products, including proteins related to the extracellular matrix, proteins
      associated with the regulation of osmotic pressure and metal transport, proteins
      related to cell survival, MAP kinase activators, proteins involved in the
      transport of retinol and vitamin D, antioxidant and antimicrobial proteins,
      intracellular proteins and some unknown proteins. Most of these gene products are
      involved in the regulation of developmental processes during embryogenesis in
      systems other than E-CSF. Interestingly, 14 of them are also present in adult
      human CSF proteome, and it has been reported that they are altered in the CSF of
      patients suffering neurodegenerative diseases and/or neurological disorders.
      Understanding these molecules and the mechanisms they control during embryonic
      neurogenesis is a key contribution to the general understanding of CNS
      development, and may also contribute to greater knowledge of these human
      diseases.

PMID- 16287171
TI  - Proteomic studies of the thylakoid membrane of Synechocystis sp. PCC 6803.
AB  - Purified thylakoid membranes from the cyanobacterium Synechocystis sp. PCC 6803
      were used for the first time in proteomic studies. The membranes were prepared by
      a combination of sucrose density centrifugation and aqueous polymer two-phase
      partitioning. In total, 76 different proteins were identified from 2- and 1-D
      gels by MALDI-TOF MS analysis. Twelve of the identified proteins have a predicted
      Sec/Tat signal peptide. Fourteen of the proteins were known, or predicted to be,
      integral membrane proteins. Among the proteins identified were subunits of the
      well-characterized thylakoid membrane constituents Photosystem I and II, ATP
      synthase, cytochrome b6f-complex, NADH dehydrogenase, and phycobilisome complex.
      In addition, novel thylakoid membrane proteins, both integral and peripheral were
      found, including enzymes involved in protein folding and pigment biosynthesis.
      The latter were the chlorophyll biosynthesis enzymes, light-dependent
      protochlorophyllide reductase and geranylgeranyl reductase as well as phytoene
      desaturase involved in carotenoid biosynthesis and a water-soluble carotenoid
      binding protein. Interestingly, in view of the protein sorting mechanism in
      cyanobacteria, one of the two signal peptidases type I of Synechocystis was found
      in the thylakoid membrane, whereas the second one has been identified previously
      in the plasma membrane. Sixteen proteins are hypothetical proteins with unknown
      function.

PMID- 16287173
TI  - Fibrinogen fragment D is necessary and sufficient to anchor a surface plasminogen
      activating complex in Streptococcus pyogenes.
AB  - In this study, the importance of different domains of the fibrinogen molecule in
      the binding and assembly of a surface plasminogen (plgn) activator has been
      analyzed. This was achieved using SELDI technology that enabled dissociation of
      bound fragments from intact bacteria and accurate distinction between fibrinogen
      fragments based on their molecular mass. These studies indicate that
      Streptococcus pyogenes binds directly to human fibrinogen fragment D but not
      fragment E. The predominant surface proteins binding to fragment D were
      associated with the mrp gene product. Surface-associated fibrinogen fragment D
      was capable of anchoring a functional surface plgn activator complex. Taken
      together, these data indicated that fragment D of fibrinogen is necessary and
      sufficient to anchor a plgn activator complex on the surface of Streptococcus
      pyogenes.

PMID- 16287172
TI  - Growth hormone (GH) receptor knockout mice reveal actions of GH in lung
      development.
AB  - The presence of growth hormone (GH) and GH receptors (GHRs) in the lung suggests
      it is an autocrine/paracrine target site for pulmonary GH action and/or an
      endocrine site of pituitary GH action. Roles for GH in lung growth or pulmonary
      function are, however, uncertain. The possibility that pituitary and/or pulmonary
      GH have physiological roles in lung development has therefore been investigated
      in GHR knockout (KO or -/-) mice, using a proteomics approach to determine if an
      absence of GH-signaling affects the proteome of the developing lung. More than
      600 proteins were detected by 2-DE in the lungs of control [GHR (+/+)] and GHR (
      /-) mice at the end of the alveolarization period (at day 14 postnatally). Of
      these, 39 differed significantly in protein content at the p>0.05 level [6 were
      of higher abundance in the GHR (-/-) group, 33 were of lower abundance] and 17
      differed at the p>0.02 level [5 of higher abundance in the GHR (-/-) group, 12 of
      lower abundance] and 7 were definitively identified by MS. Vimentin, a protein
      involved in cellular proliferation, was reduced in content by approximately 75%
      in the lungs of the GHR (-/-) mice. Three proteins involved in oxidative
      protection [SH3 domain-binding glutamic acid-rich-like protein, peroxiredoxin 6
      (Prdx6), and isocitrate dehydrogenase 1] were also of lower content in the GHR (
      /-) lungs (by approximately 88%, 81% and 70%, respectively). Prdx6 is also
      involved in lipid and surfactant metabolism, as is apolipoprotein A-IV, the lung
      content of which was reduced by approximately 73% in these mice. Proteasome 26S
      ATPase subunit 4, a protein involved in the non-lysosomal degradation of
      intracellular proteins, and electron flavoprotein alpha subunit , involved in
      intracellular metabolism, were also reduced in content in the lungs of the GHR (
      /-) mice (by approximately 70% and 49%, respectively). These results therefore
      suggest that these proteins are normally dependent upon GH signaling, and that GH
      is normally involved in early lung growth, oxidative protection, lipid and energy
      metabolism and in proteasomal activity. These roles may reflect endocrine actions
      of pituitary GH and/or local autocrine/paracrine actions of GH produced within
      the lung.

PMID- 16287174
TI  - Detection of the R553X DNA single point mutation related to cystic fibrosis by a
      "chiral box" D-lysine-peptide nucleic acid probe by capillary electrophoresis.
AB  - In order to recognize the presence of the R553X point mutation of the cystic
      fibrosis (CF) gene in the human genome, a peptide nucleic acid (PNA)
      complementary to the mutated gene tract and bearing three adjacent chiral
      monomers based on D-lysine (chiral box) was synthesized and used as a probe in
      CE. Binding specificity was preliminarily studied with complementary and
      mismatched oligonucleotides by UV spectroscopy, electrospray MS, and
      electrophoresis, indicating a very high sequence selectivity. The chiral PNA
      probe was then hybridized to cyanine-5-labeled DNA samples (186 bp), obtained by
      PCR amplification, respectively, from: (a) normal homozygous subjects (wtDNA),
      (b) CF-affected homozygous subjects (mutDNA), (c) heterozygous subjects (healthy
      carriers) and denatured at low ionic strength. The PNA-DNA mixture was directly
      analyzed by CE with LIF detection: a new signal corresponding to the PNA-mutDNA
      duplex was observed, in the case of CF-affected homozygous subjects, whereas for
      the sample containing the mismatched sequence (normal homozygous wtDNA) only the
      signal corresponding to ssDNA (ss, single strand) was detected. In the case of
      heterozygous DNA, both PNA-mutDNA duplex and ssDNA were detected. With this
      simple assay, it was possible to discriminate in an easy way among the three
      cases (mutated homozygous, normal homozygous, and heterozygous subjects) with a
      total specificity, thus allowing a decisive advance for the diagnosis of CF.

PMID- 16287175
TI  - Mutation scanning-coupled analysis of haplotypic variability in mitochondrial DNA
      regions reveals low gene flow between human and porcine Ascaris in endemic
      regions of China.
AB  - Haplotypic variation within and among the Ascaris populations representing six
      provinces in China was investigated. Mitochondrial DNA regions in the cytochrome
      c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 (nad1) genes were
      amplified by PCR from total genomic DNA samples (n > 720) from Ascaris
      individuals from humans and pigs, and subjected to mutation scanning and
      subsequent selective sequencing. For the cox1, ten different electrophoretic
      profiles were recorded for human Ascaris, and the same number for pig Ascaris,
      one of them being common to both host species. For the nad1, 11 different
      profiles were detected for human Ascaris, and 15 for pig Ascaris. Having defined
      all haplotypes (20 for pcox1 and 26 for pnad1) by sequencing, their frequencies
      were estimated in each of the two host species and each of the six provinces. For
      each mitochondrial region, the frequency of the different haplotypes varied
      considerably, depending on host species and geographical origin. Analysis of the
      sequence data (representing all haplotypes for each mitochondrial locus) by F
      statistics indicated restricted gene flow between human Ascaris and pig Ascaris,
      and supported the conclusions from previous molecular epidemiological
      investigations that pigs are not a significant source of Ascaris infection in
      humans in endemic regions.

PMID- 16287176
TI  - Internal electrolyte temperatures for polymer and fused-silica capillaries used
      in capillary electrophoresis.
AB  - Polymers are important as materials for manufacturing microfluidic devices for
      electrodriven separations, in which Joule heating is an unavoidable phenomenon.
      Heating effects were investigated in polymer capillaries using a CE setup. This
      study is the first step toward the longer-term objective of the study of heating
      effects occurring in polymeric microfluidic devices. The thermal conductivity of
      polymers is much smaller than that of fused silica (FS), resulting in less
      efficient dissipation of heat in polymeric capillaries. This study used
      conductance measurements as a temperature probe to determine the mean electrolyte
      temperatures in CE capillaries of different materials. Values for mean
      electrolyte temperatures in capillaries made of New Generation FluoroPolymer
      (NGFP), poly-(methylmethacrylate) (PMMA), and poly(ether ether ketone) (PEEK)
      capillaries were compared with those obtained for FS capillaries. Extrapolation
      of plots of conductance versus power per unit length (P/L) to zero power was used
      to obtain conductance values free of Joule heating effects. The ratio of the
      measured conductance values at different power levels to the conductance at zero
      power was used to determine the mean temperature of the electrolyte. For each
      type of capillary material, it was found that the average increase in the mean
      temperature of the electrolyte (DeltaT(Mean)) was directly proportional to P/L
      and inversely proportional to the thermal conductivity (lambda) of the capillary
      material. At 7.5 W/m, values for DeltaT(Mean) for NGFP, PMMA, and PEEK were
      determined to be 36.6, 33.8, and 30.7 degrees C, respectively. Under identical
      conditions, DeltaT(Mean) for FS capillaries was 20.4 degrees C.

PMID- 16287177
TI  - Analysis of the lipophilic peptaibol alamethicin by nonaqueous capillary
      electrophoresis-electrospray ionization-mass spectrometry.
AB  - The microheterogeneous peptaibol alamethicin F30 isolated from the culture broth
      of Trichoderma viride was analyzed by nonaqueous CE-electrospray-MS using an IT
      and a TOF mass analyzer. Compared to aqueous buffers, higher separation
      selectivity was observed for methanolic BGE allowing the detection of more minor
      components. The low electrophoretic mobility observed for neutral analytes under
      nonaqueous conditions may be explained by ion-dipole interactions between the
      peptide analytes and electrolyte ions. The amino acid sequences of the individual
      components were derived from MS(n) using the doubly or triply charged
      pseudomolecular ions as well as characteristic fragments as precursor ions. The
      exchange of Ala by alpha-aminoisobutyric acid (Aib) which is frequently observed
      for peptaibols was detected for several components. Additional variations
      included the exchange of Gln to Glu, and the loss of the C-terminal amino alcohol
      or of the first six amino acids from the N-terminus with concomitant formation of
      pyroglutamyl residues. In most cases comigration of the Aib peptaibols with the
      respective Ala component was observed as the mass difference of 14 Da as the
      result of the amino acid exchange was not sufficient to translate into an
      electrophoretic separation under the conditions applied. However, proper
      selection of the precursor ions allowed the unequivocal analysis of the
      components. Additional TOF-MS measurements were performed in order to resolve the
      ammonium adducts from comigrating compounds (i.e., Aib-Ala exchange) and to
      confirm the amino acid composition of the individual components. Except for
      neutral compounds migrating close to the EOF the mass accuracy was better than 4
      ppm for the doubly charged pseudomolecular ions and better than 2 ppm for triply
      charged ions.

PMID- 16287179
TI  - Organosulfur compounds: electrophilic reagents in transition-metal-catalyzed
      carbon-carbon bond-forming reactions.
AB  - Transition-metal-catalyzed carbon-carbon bond-forming reactions are among the
      most powerful methods in organic synthesis and play a crucial role in modern
      materials science and medicinal chemistry. Recent developments in the area of
      ligands and additives permit the cross-coupling of a large variety of reactants,
      including inexpensive and readily available sulfonyl chlorides. Their
      desulfitative carbon-carbon cross-coupling reactions (Negishi, Stille,
      carbonylative Stille, Suzuki-Miyaura, and Sonogashira-Hagihara-type cross
      couplings and Mizoroki-Heck-type arylations) are reviewed together with carbon
      carbon cross-coupling reactions with other organosulfur compounds as
      electrophilic reagents.

PMID- 16287181
TI  - A statistical model for unwarping of 1-D electrophoresis gels.
AB  - A statistical model is proposed which relates density profiles in 1-D
      electrophoresis gels, such as those produced by pulsed-field gel electrophoresis
      (PFGE), to databases of profiles of known genotypes. The warp in each gel lane is
      described by a trend that is linear in its parameters plus a first-order
      autoregressive process, and density differences are modelled by a mixture of two
      normal distributions. Maximum likelihood estimates are computed efficiently by a
      recursive algorithm that alternates between dynamic time warping to align
      individual lanes and generalised-least-squares regression to ensure that the warp
      is smooth between lanes. The method, illustrated using PFGE of Escherichia coli
      O157 strains, automatically unwarps and classifies gel lanes, and facilitates
      manual identification of new genotypes.

PMID- 16287182
TI  - Direct chemiluminescent imaging detection of Cu/Zn-superoxidase dismutase,
      glutathione peroxidase, carbonic anhydrase-III, and catalase in rat liver cytosol
      separated by native porous gradient polyacrylamide gel electrophoresis.
AB  - The cytosolic enzymes extracted from rat hepatocytes were separated by native
      porous gradient-PAGE (PG-PAGE) and were detected with a sensitive and fast
      chemiluminescence (CL) imaging method. Several peroxidases including glutathione
      peroxidase, Cu/Zn-superoxidase dismutase, and some other metallo-enzymes such as
      catalase, carbonic anhydrase-III (CA-III) present in the cytosol of rat
      hepatocytes have been selectively and sensitively detected by the direct CL
      imaging method using the luminol-H(2)O(2) chemiluminescent reagents. All
      detections after PG-PAGE were completed within 9 min. The linear range for the
      typical metallo-enzyme, e.g., CA-III is 0.75-4.9 microg/mL, with a detection
      limit of 0.25 microg/mL. In comparison with the traditional CBB-R250 staining
      method, the detection period decreased about 70 times and the detection
      sensitivity improved over ten times. Furthermore, two enzymes present in rat
      liver cytosol were identified employing MALDI-MS analysis of the tryptic digest
      after PG-PAGE.

PMID- 16287183
TI  - An online fiber-optic UV-visible detector for continuous free-flow
      electrophoresis.
AB  - A PC-controlled, scanning online UV detector for continuous free-flow
      electrophoresis (CFFE) was designed to allow for single UV wavelength monitoring
      across a 1-D array of 48 longitudinal flow cells interfaced to a CFFE apparatus.
      In the detection scheme, the UV light is sequentially passed through each of the
      flow cells. The design integrates online acquisition of absorbance spectra of
      components separated by CFFE. Benzoic acid standard solutions were used to
      examine the performance of the detector. Chloroquine diphosphate and 4
      nitrophenol were used as test solutes to determine the detector's ability to
      distinguish analytes separated in the CFFE.

PMID- 16287184
TI  - Analysis of electrophoretic patterns of arbitrarily primed PCR profiling.
AB  - We present a mathematical algorithm for the analysis of electrophoretic patterns
      resulting from arbitrarily primed PCR profiling. The algorithm is based on the
      established mathematical procedures applied to the analysis of digital images of
      gel patterns. The algorithm includes (a) transformation of the image into a
      matrix form, (b) identification of every electrophoretic lane as a set of matrix
      columns that are further mathematically processed, (c) averaging of matrix
      columns corresponding to electrophoretic lanes that define lane representatives,
      (d) elimination of "smiling" bands, (e) solving the problem of a lane offset, and
      (f) removal of the background. Representation of individual electrophoretic lanes
      in the form of functions allows interlane comparisons and further mathematical
      analysis. Direct comparison of selected lanes was obtained by employing
      correlation analysis. Gel images were those obtained after arbitrarily primed PCR
      analysis of DNA that underwent damage induced by gamma radiation from a (60)Co
      source. The applied method proved to be useful for elimination of subjectivity of
      visual inspection. It offers the possibility to avoid overlooking important
      differences in case of suboptimal electrophoretic resolution. In addition, higher
      precision is achieved in the assessment of quantitative differences due to better
      insight into experimental artifacts. These simple mathematical methods offer an
      open-type algorithm, i.e., this algorithm enables easy implementation of
      different parameters that may be useful for other analytical needs.

PMID- 16287185
TI  - Rapid differentiation of Fusarium oxysporum isolates using PCR-SSCP with the
      combination of pH-variable electrophoretic medium and low temperature.
AB  - Differentiation of Fusarium oxysporum is significantly important for unraveling
      the pathogenetic mechanism of Fusaria wilts. In this study, isolates of F.
      oxysporum were screened from the soils in the rhizosphere of watermelon plant by
      Komada medium and differentiated by SSCP approach with the combination of pH
      variable electrophoretic medium (Tris-MES-EDTA (TME), pH 6.1) and low temperature
      (9 degrees C). We found that TME was a good electrophoretic medium and its pH
      value was variable over the course of electrophoresis in our apparatus. The pH
      variable electrophoretic medium made more contribution for the better
      differentiation of F. oxysporum isolates than low temperature. The combination of
      TME pH 6.1 and low temperature showed an improved effect on resolution of ssDNAs.
      Leaving partial nondenatured dsDNA for SSCP was advantageous for differentiation
      of F. oxysporum isolates. The SSCP patterns of F. oxysporum isolates proved to be
      highly reproducible. Sequencing data confirmed that this SSCP method could detect
      one single base change within the 550 bp PCR fragment from the ribosomal internal
      transcribed spacer region of F. oxysporum.

PMID- 16287186
TI  - Recovery of intact yeast chromosomal DNA from agarose gel plugs using coil
      globule transition.
AB  - In the current studies, we designed a new approach for sizing and isolating
      chromosomal DNA using coil-globule transition, which avoids fragmentation of
      giant DNA due to mechanical stress. Although coil-globule transition is
      reversible and globular DNA is tolerant to mechanical stress, globular DNA cannot
      be manipulated by an electric field because of the loss of its negative charges.
      In our system, however, DNA is extracted from an agarose gel in a coiled state
      into a solution of PEG, and coil-globule transition is induced by cations
      generated at the anode. This method achieves buffer exchange without stirring,
      which is the main cause of mechanical stress. Real-time analysis of T4dc viral
      DNA molecules revealed that they change immediately from a coiled to a globular
      form when the cation concentration is sufficiently high. This method was used to
      prepare yeast chromosomal DNA in a globular state without fragmentation.

PMID- 16287188
TI  - Si8(SitBu3)6: a hitherto unknown cluster structure in silicon chemistry.

PMID- 16287187
TI  - Catalytic asymmetric tandem transformations triggered by conjugate additions.
AB  - The development of efficient methods to access complex molecules with
      multistereogenic centers has been a substantial challenge in both academic
      research and industrial applications. One approach to this challenge is catalytic
      asymmetric tandem transformations, which allow a rapid increase in molecular
      complexity from readily available starting materials to produce enantiopure
      compounds. In recent years, considerable efforts have been directed towards the
      development of asymmetric tandem transformations. This Minireview highlights
      recent developments and the applications of metal-catalyzed and organocatalytic
      asymmetric tandem transformations triggered by conjugate additions.

PMID- 16287189
TI  - The photochemistry of o-nitrobenzaldehyde as seen by femtosecond vibrational
      spectroscopy.

PMID- 16287190
TI  - Azine-bridged octanuclear copper(II) complexes assembled with a one-stranded
      ditopic thiocarbohydrazone ligand.

PMID- 16287191
TI  - Interpenetrating copper-silver cyanometallate networks: polymorphs and
      topological isomers.

PMID- 16287192
TI  - High-temperature synthesis of the surprisingly stable C1-C70(CF3)10 isomer with a
      para7-meta-para ribbon of nine C6(CF3)2 edge-sharing hexagons.

PMID- 16287193
TI  - An unexpected photoelectronic effect from [Co(en)3]2(Zr2F12)(SiF6)4 H2O, a
      compound containing an H-bonded assembly of discrete [Co(en)3]3+, (Zr2F12)4-, and
      (SiF6)2- ions.

PMID- 16287194
TI  - Characteristics of boron nitride nanotube-polyaniline composites.

PMID- 16287195
TI  - Acquisition of human cytomegalovirus infection in infants via breast milk:
      natural immunization or cause for concern?
AB  - Since the recognition in the 1960s that human cytomegalovirus (HCMV) infections
      could be transmitted by breast milk, there has been relatively little attention
      paid to the potential medical consequences of such infections. Indeed, since HCMV
      infections acquired by healthy newborn infants appear to be largely asymptomatic
      in nature, there has been no real incentive to develop or implement strategies to
      prevent transmission by this route. However, recent studies have identified a
      significant risk for low-birth weight, premature infants for the development of
      HCMV disease following acquisition of infection via breast milk. Such infections
      may cause considerable short-term morbidity and, in some cases, severe, life
      threatening illness. There is little consensus amongst neonatologists on the
      approach to prevention and management of such infections. This review summarises
      the epidemiology and natural history of HCMV infections acquired via breast milk,
      and outlines available strategies for prevention and management of such
      infections, as well as opportunities for future clinical research on this
      understudied topic.

PMID- 16287196
TI  - Audience responses to a research-based drama about life after breast cancer.
AB  - This article explores audience reactions to the research-based drama Ladies in
      Waiting? Life After Breast Cancer. Quantitative findings indicate an
      overwhelmingly positive response, with approximately 90% of those who saw the
      production agreeing that they benefited from seeing it and indicating that they
      would recommend it to others. Qualitative data reveal a more complex picture of
      the range of reactions, allowing us to describe the most valued aspects of the
      production (mainly how it eased isolation and normalized the difficult aspects of
      survivorship) and to better understand the few reports of distress. Audience
      responses to Ladies in Waiting? suggest that chronic aspects of breast cancer are
      rarely acknowledged. Viewing the production as one that reveals difficult and
      hidden realities allows for a fuller understanding both of its supportive and
      unsettling effects.

PMID- 16287197
TI  - Body image and sexual problems in young women with breast cancer.
AB  - PURPOSE: The purpose of this study was to determine the frequency of body image
      and sexual problems in the first months after treatment among women diagnosed
      with breast cancer at age 50 or younger. BACKGROUND: Breast cancer treatment may
      have severe effects on the bodies of younger women. Surgical treatment may be
      disfiguring, chemotherapy may cause abrupt menopause, and hormone replacement is
      not recommended. METHODS: A multi-ethnic population-based sample of 549 women
      aged 22-50 who were married or in a stable unmarried relationship were
      interviewed within seven months of diagnosis with in situ, local, or regional
      breast cancer. RESULTS: Body image and sexual problems were experienced by a
      substantial proportion of women in the early months after diagnosis. Half of the
      546 women experienced two or more body image problems some of the time (33%), or
      at least one problem much of the time (17%). Among sexually active women, greater
      body image problems were associated with mastectomy and possible reconstruction,
      hair loss from chemotherapy, concern with weight gain or loss, poorer mental
      health, lower self-esteem, and partner's difficulty understanding one's feelings.
      Among the 360 sexually active women, half (52%) reported having a little problem
      in two or more areas of sexual functioning (24%), or a definite or serious
      problem in at least one area (28%). Greater sexual problems were associated with
      vaginal dryness, poorer mental health, being married, partner's difficulty
      understanding one's feelings, and more body image problems, and there were
      significant ethnic differences in reported severity. CONCLUSIONS: Difficulties
      related to sexuality and sexual functioning were common and occurred soon after
      surgical and adjuvant treatment. Addressing these problems is essential to
      improve the quality of life of young women with breast cancer.

PMID- 16287198
TI  - Antibiotic resistant fecal isolates of Enterococci among unselected patients
      outside the clinical sector: an epidemiological study from Southern Germany.
AB  - PURPOSE: The aim of the study was to assess the prevalence and determinants of
      antibiotic-resistant Enterococci in a large group of outpatients in Southern
      Germany. METHODS: Stool samples were collected from 497 unselected patients aged
      40-75 years attending general practitioners. Enterococcus faecium (E. faecium)
      and Enterococcus faecalis (E. faecalis) were cultured and minimal inhibitory
      concentrations of antibiotics used inside and outside the clinical sector were
      tested. RESULTS: E. faecium and E. faecalis could be identified and cultured in
      60 (12.4%) and 205 (41.2%) of the stool samples, respectively. Under non
      selective culture conditions no vancomycin-resistant Enterococcus (VRE) isolate
      was found. Only E. faecium isolates showed resistance to fluoroquinolones, 40%
      were resistant to ciprofloxacin. The prevalences of E. faecium resistance to
      ampicillin and doxycycline were 3.3% and 13.3%, respectively, whereas 0.5% and
      29.6% of the E. faecalis isolates were resistant to ampicillin and doxycycline,
      respectively. Antibiotic use during the last 3 months was significantly
      associated with antibiotic resistance (to either ampicillin, imipenem, or
      doxycycline) of E. faecalis isolates (OR: 2.9; CI: 1.2-6.8). CONCLUSIONS:
      Prevalences of resistance were generally lower than and patterns of resistance
      were quite different from previous investigations in the clinical setting. Recent
      antibiotic use was associated with increased colonization with resistant strains.

PMID- 16287199
TI  - Prevalence, incidence and persistence of antipsychotic drug prescribing in the
      Italian general population: retrospective database analysis, 1999-2002.
AB  - PURPOSE: To investigate the prevalence, incidence and persistence with
      antipsychotic drug therapy in a large and geographically defined catchment area
      of Italian general population. METHODS: All antipsychotic drug prescriptions
      dispensed during 1999, 2000, 2001 and 2002 were extracted from an administrative
      prescription database covering a population of 2 640 379 individuals.
      Antipsychotic drug users were defined as patients who had at least one recorded
      prescription in the current year. New users were defined as patients receiving a
      first prescription without any recorded antipsychotic drug treatment in the
      previous 12 months. Prevalence data were calculated by dividing users by the
      total number of male and female residents in each age group. Incidence data were
      calculated as the number of new users divided by the person-time free from
      antipsychotic drugs in the current year. The cumulative persistence of each
      medication was calculated by dividing the total prescribed amount of
      antipsychotic drug by the recommended daily dose, according to each agent's
      defined daily dose (DDD). RESULTS: A progressive rise in prevalence and incidence
      rates was observed during the 4-year period. In each census year, the prevalence
      and incidence of prescribing was higher in females than males, and progressively
      rose with age, with the highest rates in old and very old subjects. The analysis
      of persistence with therapy revealed that 3176 individuals (78.5%) were
      occasional antipsychotic drug users, and that occasional use was more frequent
      among individuals receiving conventional antipsychotic drugs than among
      individuals receiving novel antipsychotic drugs. This difference was not
      explained by differences in the occurrence of neurologic adverse reactions, as
      shown by the concurrent prescribing of anticholinergic drugs, which was fairly
      similar between the two groups of new drug users. Additionally, we found that
      conventioal antipsychotic drugs were more often used in older individuals, where
      occasional use is very frequent, while novel antipsychotic drugs were more often
      prescribed in young and adult individuals, where regular use is more frequent.
      CONCLUSIONS: An epidemiologically relevant proportion of everyday individuals is
      annually exposed to antipsychotic drugs. The distribution of prevalence and
      incidence rates by age highlighted an emerging public health issue related to the
      adverse and beneficial consequences of antipsychotic drug exposure in the
      elderly. The finding that persistence with therapy was longer in new users of
      novel antipsychotic drugs compared with new users of conventional agents might be
      explained by the different demographic and clinical characteristics of
      individuals receiving these two drug classes and not by the different
      tolerability profile of these two drug classes.

PMID- 16287200
TI  - Adverse drug reactions in hospitalized children in Fortaleza, Brazil.
AB  - PURPOSE: To investigate the occurrence of adverse drug reactions (ADRs) and
      associated risk factors in a pediatric hospital in northeast Brazil, from August
      to December 2001. SUBJECTS/SETTING: Two hundred seventy two patients hospitalized
      for more than 24 hours. METHODS: Prospective cohort study. Daily visits were
      performed for inclusion or attendance of patients and collection of information
      on drug prescriptions and medical events. The visits were focused on the
      detection of adverse events. WHO categories were used to assess the imputability
      and severity of suspected ADRs. RESULTS: Two hundred sixty five patients (97%)
      were exposed to medicines during hospitalization; the most frequent diagnosis was
      pneumonia (30%), the therapeutic class most prescribed was anti-infectives for
      systemic use (26%). Of a total of 420 adverse events, 47 ADRs were detected in 33
      of 265 children treated with drugs. The cumulative incidence of ADRs was 12.5%
      (33/265); incidence density was 8 events per 1000 patient days (33/4042 patient
      days). The skin was the most affected organ (49%); the drugs more implicated were
      systemic antibiotic (53.2%). The ADRs were mild or moderate in 97.9% of cases;
      causality was probable in 57.5% and the majority of events were independent of
      the dose given (55.3%). In multivariate analysis, the risk of ADR increased with
      the number of drugs, male gender, and > or =3 previous hospitalization courses.
      CONCLUSION: ADRs are not uncommon among hospitalized children, particularly those
      with prior histories of hospitalization and concomitant use of several medicines.

PMID- 16287202
TI  - Estimating the parameters of the operational model of pharmacological agonism.
AB  - The aim of this work is practical. We show that the parameters of the widely used
      operational model of pharmacological agonism are difficult to estimate from
      single dose-response curves. The parameters can be estimated using pairs of dose
      response curves (usually treatment and control) sharing some parameters.
      Confidence bands for the estimators are developed. In the case of multiple dose
      response curve pairs one can employ a non-linear mixed effects model to allow for
      inter-individual variation. The point estimates and the confidence intervals thus
      obtained are similar to the more naive construction based on mean and standard
      errors of parameter estimates. To test for difference of certain parameters
      between treatment and control we employ a permutation test and Wald's test.

PMID- 16287201
TI  - Sample size calculations for disease freedom and prevalence estimation surveys.
AB  - We developed a Bayesian approach to sample size calculations for studies designed
      to estimate disease prevalence that uses a hierarchical model for estimating the
      proportion of infected clusters (cluster-level prevalence) within a country or
      region. The clusters may, for instance, be villages within a region, cities
      within a state, or herds within a country. Our model allows for clusters with
      zero prevalence and for variability in prevalences among infected clusters.
      Moreover, uncertainty about diagnostic test accuracy and within-cluster
      prevalences is accounted for in the model. A predictive approach is used to
      address the issue of sample size selection in human and animal health surveys. We
      present sample size calculations for surveys designed to substantiate freedom of
      a region from an infectious agent (disease freedom surveys) and for surveys
      designed to estimate cluster-level prevalence of an endemic disease (prevalence
      estimation surveys). In disease freedom surveys, for instance, assuming the
      cluster-level prevalence for a particular infectious agent in the region is
      greater than a maximum acceptable threshold, a sample size combination consisting
      of the number of clusters sampled and number of subjects sampled per cluster can
      be determined for which authorities conducting the survey detect this excessive
      cluster-level prevalence with high predictive probability. The method is
      straightforward to implement using the Splus/R library emBedBUGS together with
      WinBUGS.

PMID- 16287203
TI  - Bootstrap-based methods for testing factor-by-curve interactions in generalized
      additive models: assessing prefrontal cortex neural activity related to decision
      making.
AB  - In many situations the effect of a continuous covariate on response varies across
      groups defined by levels of a categorical variable. This paper addresses
      generalized additive models incorporating the so-called factor-by-curve
      interaction. A local scoring algorithm based on local linear kernel smoothers was
      used to estimate the model. Two different types of bootstrap-based procedures are
      proposed for testing interaction terms, namely, the likelihood ratio test, and a
      procedure based on an estimate of the interaction terms. Given the high
      computational cost involved, binning techniques were used to speed up computation
      in the estimation and testing processes. A simulation study was conducted to
      assess the validity of these bootstrap-based tests. This methodology was applied
      to studying prefrontal cortex neural activity associated with decision-making in
      monkeys. The proposed statistical procedure proved very useful in revealing the
      neural activity correlates of decision-making strategies adopted by monkeys in
      accordance with different behavioural tasks.

PMID- 16287204
TI  - Human papillomaviruses: basic mechanisms of pathogenesis and oncogenicity.
AB  - Human papillomaviruses (HPVs) are small double-stranded DNA viruses that infect
      the cutaneous and mucosal epithelium. Infection by specific HPV types has been
      linked to the development of cervical carcinoma. HPV infects epithelial cells
      that undergo terminal differentiation and so encode multiple mechanisms to
      override the normal regulation of differentiation to produce progeny virions. Two
      viral proteins, E6 and E7, alter cell cycle control and are the main arbitrators
      of HPV-induced oncogenesis. Recent data suggest that E6 and E7 also play a major
      role in the inhibition of the host cell innate immune response to HPV. The E1 and
      E2 proteins, in combination with various cellular factors, mediate viral
      replication. In addition, E2 has been implicated in both viral and cellular
      transcriptional control. Despite decades of research, the function of other viral
      proteins still remains unclear. While prophylactic vaccines to block genital HPV
      infection will soon be available, the widespread nature of HPV infection requires
      greater understanding of both the HPV life cycle as well as the mechanisms
      underlying HPV-induced carcinogenesis.

PMID- 16287206
TI  - Estimating vaccine effects from studies of outbreaks in household pairs.
AB  - The traditional way to measure efficacy of a vaccine, with respect to reduced
      susceptibility and reduced infectivity once infected, is to look at relative
      attack rates. Although straightforward to apply, such measures do not take
      disease transmission into account, with the consequence that they can depend
      strongly on the community setting, the duration of the study period, the way
      participants are recruited into the study and the virulence of the infection.
      Sometimes they give a very misleading assessment of the vaccine, as we illustrate
      by examples. Here measures of vaccine efficacy are considered that avoid these
      defects, and estimation procedures are presented for studies based on outbreaks
      in household pairs. Such studies enable estimation of vaccine effects on
      susceptibility, infectivity and transmission. We propose that the vaccine
      efficacy measures be estimated, without making any assumptions about the nature
      of the vaccine response, by consistent estimates of bounds for the measures.

PMID- 16287205
TI  - Lipid peroxidation and some antioxidant enzymes in nasal polyp tissue.
AB  - Nasal polyp (NP) is considered an inflammatory condition in nasal and paranasal
      sinus cavities and is frequently encountered in otolaryngology clinics. Although
      the pathophysiology of nasal polyps is poorly understood, it seems likely that
      the epithelium may play a critical role in the genesis of inflammatory nasal
      disease. The aim of this study was to investigate the role of free radicals and
      antioxidant enzymes in NP and compare these findings with concha bullosa (CB). NP
      and CB were obtained from 27 and 23 patients, respectively. Glutathione
      peroxidase (GSH-Px), catalase (CAT), xanthine oxidase (XO) total (enzymic plus
      non-enzymic) superoxide scavenger activity (TSSA), non-enzymic superoxide
      scavenger activity (NSSA), superoxide dismutase (SOD), and MDA levels in NP and
      CB were measured. GSH-Px activiy was significantly lower in patients with NP than
      in the CB group. However, CAT, XO activities and MDA levels were significantly
      higher in patients with NP than in the CB group, but TSSA, NSSA and SOD
      activities were unchanged. Increases in the levels of tissue MDA in patients with
      NP compared to the CB group may indicate the presence of free radical damage in
      patients with nasal NP.

PMID- 16287207
TI  - Development and initial validation of a family appraisal of caregiving
      questionnaire for palliative care.
AB  - This article describes the derivation and initial psychometric validation of a
      multi-dimensional Family Appraisal of Caregiving Questionnaire for Palliative
      Care (FACQ-PC). The 25-item measure consists of four theoretically derived
      subscales: (i) caregiver strain, (ii) positive caregiving appraisals, (iii)
      caregiver distress, and (iv) family well-being. Based on a sample of 160 family
      caregivers of a relative with cancer receiving palliative care, reliability
      analyses demonstrated the subscale scores to be internally consistent and factor
      analysis revealed evidence of factorial validity. Correlations of the four
      subscales with measures of family functioning, positive and negative affect, and
      subjective burden provided evidence of convergent and discriminant validity. The
      FACQ-PC provides a measure of the family's appraisal of caregiving that can be
      used in clinical assessment, and has potential utility for evaluating the
      effectiveness of palliative care interventions.

PMID- 16287208
TI  - Mechanisms of action of ribavirin against distinct viruses.
AB  - The nucleoside analogue ribavirin has antiviral activity against many distinct
      viruses both in vitro and in vivo. Five distinct mechanisms have been proposed to
      explain the antiviral properties of ribavirin. These include both indirect
      mechanisms (inosine monophosphate dehydrogenase inhibition, immunomodulatory
      effects) and direct mechanisms (interference with RNA capping, polymerase
      inhibition, lethal mutagenesis). Recent concerns about bioterrorism have renewed
      interest in exploring the antiviral activity of ribavirin against unique viruses.
      In this paper, we review the proposed mechanisms of action with emphasis on
      recent discoveries, as well as the implications of ribavirin resistance. Evidence
      exists to support each of the five proposed mechanisms of action, and distinct
      virus/host combinations may preferentially favour one or more of these mechanisms
      during antiviral therapy.

PMID- 16287209
TI  - Optimism, social support and psychosocial functioning among women with breast
      cancer.
AB  - Personality, psychosocial, demographic and medical variables have been identified
      as correlates of adjustment to breast cancer and quality of life (QoL). Most
      studies have examined relationships between personality, social support and
      adjustment to cancer in predominantly middle-class Caucasian samples, thus
      limiting the generalizability of their findings. Eighty-one female outpatients at
      a medical oncology breast clinic in a county general hospital serving primarily
      indigent Hispanic and African-American patients completed measures assessing
      demographic and medical information, health-related QoL, cancer-specific
      distress, mood disturbance, dispositional optimism and satisfaction with social
      support. Older age, receipt of treatment and greater optimism accounted for 41%
      of the variance in emotional well-being (p<0.01). Absence of family history of
      breast cancer, receipt of treatment and optimism accounted for 43% of the
      variance in functional well-being (p<0.01). Optimism and satisfaction with social
      support accounted for 43% of the variance in social/family well-being (p<0.01).
      Absence of treatment (not yet treated) and pessimism accounted for 31% of the
      variance in cancer-specific distress (p<0.01). Finally, family history of breast
      cancer and pessimism accounted for 48% of the variance in mood disturbance
      (p<0.001). Family history of breast cancer and pessimism were related to mood
      disturbance (p<0.001). No between-group differences were found for race/ethnicity
      for any of the variables. Encouraging positive expectations and facilitating
      social support may help women in public sector medical settings cope with the
      stressful demands of diagnosis and treatment of breast cancer regardless of
      race/ethnicity.

PMID- 16287211
TI  - Exposure-time-varying hazard function ratios in case-control studies of drug
      effects.
AB  - For many adverse effects of drugs, the instantaneous risk of an incident event
      per day of therapy (i.e., the hazard function) varies by duration of therapy and
      by prior exposure. In cohort studies of adverse drug effects time-varying hazard
      functions are easily modeled using standard statistical software packages. Tests
      of the hypothesis of a constant proportional hazard function ratio are also
      available. In case control studies, the need to consider time-varying hazard
      functions seems to be somewhat less well-recognized than in cohort studies. When
      the hazard function ratio for an adverse drug event is not constant over time, an
      overall single odds ratio (OR) estimated in a case control study not accounting
      for the time variation in the hazard function is a weighted average of duration
      specific ORs with weights reflecting the distribution of exposure time in the
      study population. The resulting estimate depends not only on the drug but also on
      the exposure time distribution in the study population. This can lead to
      misleading conclusions when comparing the risks of two drugs within the same
      population and when comparing risks of the same drug in different populations.
      Analytic approaches for addressing time-varying hazard functions in case-control
      studies have been published but seem to be less used than in cohort studies. This
      article discusses adverse drug effects with time-varying hazard functions and
      methods for addressing these in case-control studies during study design, data
      collection, and analysis.

PMID- 16287210
TI  - Social constraints and spousal communication in lung cancer.
AB  - The Social Cognitive Processing Model suggests that talking with others
      facilitates cognitive and emotional processing of experiences such as cancer if
      the social context in which these discussions take place is supportive and
      positive. Despite this, patients and spouses may inadvertently constrain each
      other's attempts to process and cope with the disease. To our knowledge, no
      previous studies have directly examined the effect of lung cancer on the spousal
      relationship. We began to examine this effect by identifying the social
      constraints experienced by couples coping with lung cancer through semi
      structured interviews with 13 patients and 12 spouses. Using Grounded Theory
      methodology, our analyses showed that these couples experienced a wide variety of
      social constraints, including denial, avoidance, and conflict that can hinder
      open spousal communication. Specifically, patients and spouses reported trouble
      discussing continued tobacco use, cancer-related symptoms, prognosis, and the
      emotional effects of lung cancer on the spouse. Despite these constraints,
      participants who reported talking with their partners about their relationships
      reported fewer constraints and better communication about cancer. These findings
      highlight the importance of a relationship perspective in the study of lung
      cancer and provide information about how talking together about the spousal
      relationship may enable couples to minimize social constraints and enhance
      cognitive and emotional processing of the disease.

PMID- 16287212
TI  - Cancer incidence in a general population of asthma patients.
AB  - PURPOSE: Several studies have assessed the association between asthma and cancer
      but none of them revealed a clear pattern of association. We aimed to examine the
      association between asthma, chronic obstructive pulmonary disease (COPD), and
      cancer. METHODS: We performed a cohort study with a nested case-control analysis
      using the General Practitioner Research Database in the UK. We defined three
      cohorts: patients with asthma, patients with COPD, and general population. During
      the follow-up, we identified a total of 5263 incident cases of cancer. We
      conducted a nested case-control analysis that included all cancer cases as well
      as 20 000 controls free of cancer frequency-matched on age, sex, and calendar
      year. RESULTS: Patients with asthma did not have an overall greater risk of
      cancer compared with the general population (odds ratio = 0.93, 95% confidence
      interval (CI): 0.86-1.00). However, they presented an elevated risk of
      experiencing lung cancer (odds ratio = 1.84, 95%CI: 1.58-2.15). Controlling for
      smoking and other potential confounding factors yielded a lower estimate (odds
      ratio = 1.35, 95%CI: 1.15-1.59). This estimate contrasted with that observed for
      non-smoking related cancer (0.87, 95%CI: 0.80-0.94). Overall, respiratory drugs
      did not seem to be associated with cancer among asthmatic patients. Patients with
      COPD had an Odds ratio of cancer of 1.26 (95%CI: 1.12-1.43) compared with the
      general population. CONCLUSIONS: Asthma was not associated with an increased risk
      of cancer. In fact, the risk of non-smoking related cancer was slightly reduced.
      However, we observed a small-elevated risk of lung cancer among asthmatic
      patients. Whether this result is a due to residual confounding and/or protopathic
      bias remains unclear. Further investigation is warranted to confirm or discard
      these associations.

PMID- 16287213
TI  - Signal transduction through Ras-GTPase and Ca2+/ calmodulin-dependent protein
      kinase II contributes to development of diabetes-induced renal vascular
      dysfunction.
AB  - This study examined the role of Ca2+/calmodulin-dependent protein kinase II
      (CaMKII) and Ras-GTPase in the development of abnormal reactivity to vasoactive
      agents in the renal artery of diabetic rats. The vasoconstrictor response induced
      by norepinephrine (NE), endothelin-1 (ET-1) or angiotensin II (Ang II) was
      significantly increased whereas vasodilator response to carbachol, histamine or
      sodium nitroprusside (SNP) was not altered in the renal artery segments of the
      streptozotocin (STZ)-diabetic rats. Chronic intraperitoneal administration of KN
      93 (5 mg/kg/ alt diem), an inhibitor of CaMKII or FPTIII (1.5 mg/kg/ alt diem),
      an inhibitor of Ras-GTPase, produced significant normalization of the altered
      agonist-induced vasoconstrictor responses without affecting blood glucose levels.
      All the inhibitors were administered for four weeks starting from day one of
      diabetes induction. Inhibition of Ras-GTPase or CaMKII did not affect the agonist
      induced vasoconstrictor and vasodilator responses in the non-diabetic control
      animals. These data suggest that inhibition of signal transduction involving
      CaMKII and Ras-GTPase can prevent development of diabetes-induced abnormal
      vascular reactivity in the renal artery.

PMID- 16287214
TI  - Nitric oxide synthase activity and nitric oxide level in erythrocytes of guinea
      pigs with experimental otitis media with effusion.
AB  - Free radicals have been implicated in the pathogenesis of an increasing number of
      disease and inflammatory states. They may cause cell and tissue damage by
      chemical modification of proteins, carbohydrates, nucleotides and lipids. Under
      physiological conditions free radicals are parts of normal regulatory circuits
      and are neutralized by antioxidants. Infections are one cause of increased free
      radicals production. The aim of our study was to assess whether increased
      oxidative stress is reflected by erythrocyte nitric oxide synthase activity and
      nitric oxide levels in guinea pigs with experimental otitis media with effusion
      (n = 6) and in a control group (n = 6). Erythrocyte nitric oxide synthase
      activity and nitric oxide levels were measured in both groups. The nitric oxide
      synthase activity and nitric oxide level in the experimental otitis media with
      effusion were significantly higher than those of the control group. There was a
      significant positive correlation between the nitric oxide synthase activity and
      nitric oxide in the experimental otitis media with effusion group. Thus,
      increased nitric oxide levels may play an important role in cell and tissue
      damage due to experimental otitis media with effusion.

PMID- 16287215
TI  - Detection of anti-CD32 alloantibody in donor plasma implicated in development of
      transfusion-related acute lung injury.
AB  - Transfusion-related acute lung injury (TRALI) occasionally causes serious
      symptoms that may be fatal to recipients. Polymorphonuclear neutrophils (PMNs)
      and alloantibodies specific to PMN cell surface antigens are suspected to cause
      TRALI. The aim of this study is to establish a sensitive and stable procedure of
      detecting alloantibodies not only in donor blood, but also in recipient's plasma.
      We have introduced a new method of detecting alloantibodies based on double
      determinant enzyme-linked immunosorbent assay (DD-ELISA) and a monoclonal
      antibody-immobilized granulocyte antigen (MAIGA) test (arbitrarily designated as
      modified DD-ELISA). We verified the specificity of alloantibodies against PMN
      cell surface antigens in plasma samples from three normal healthy donors of blood
      that induced respiratory distress in recipients after a blood transfusion. Anti
      CD32 (Fc gamma RIII) alloantibodies were detected in all the plasma samples using
      two different clones of the monoclonal anti-CD32 antibody. The specificities of
      these plasma samples could not be identified by the granulocyte
      immunofluorescence test (GIFT) using typed test cells. Except for the anti-CD32
      alloantibodies, one plasma sample was proved to have the anti-HNA-1a
      alloantibodies. In another plasma sample, the anti-HNA-2a alloantibodies were
      detected. By modified DD-ELISA, we could clearly specify the presence of
      alloantibodies in the three plasma samples. Our results also suggest that the
      anti-CD32 alloantibodies can be generated in vivo and may play some roles in the
      development of TRALI.

PMID- 16287216
TI  - ITT analysis of randomized encouragement design studies with missing data.
AB  - In this paper, we considered a missing outcome problem in causal inferences for a
      randomized encouragement design study. We proposed both moment and maximum
      likelihood estimators for the marginal distributions of potential outcomes and
      the local complier average causal effect (CACE) parameter. We illustrated our
      methods in a randomized encouragement design study on the effectiveness of flu
      shots.

PMID- 16287217
TI  - An ROC-type measure of diagnostic accuracy when the gold standard is continuous
      scale.
AB  - ROC curves and summary measures of accuracy derived from them, such as the area
      under the ROC curve, have become the standard for describing and comparing the
      accuracy of diagnostic tests. Methods for estimating ROC curves rely on the
      existence of a gold standard which dichotomizes patients into disease present or
      absent. There are, however, many examples of diagnostic tests whose gold
      standards are not binary-scale, but rather continuous-scale. Unnatural
      dichotomization of these gold standards leads to bias and inconsistency in
      estimates of diagnostic accuracy. In this paper, we propose a non-parametric
      estimator of diagnostic test accuracy which does not require dichotomization of
      the gold standard. This estimator has an interpretation analogous to the area
      under the ROC curve. We propose a confidence interval for test accuracy and a
      statistical test for comparing accuracies of tests from paired designs. We
      compare the performance (i.e. CI coverage, type I error rate, power) of the
      proposed methods with several alternatives. An example is presented where the
      accuracies of two quick blood tests for measuring serum iron concentrations are
      estimated and compared.

PMID- 16287218
TI  - Deaths linked to injectable olanzapine.

PMID- 16287219
TI  - Telithromycin: another interacting macrolide.

PMID- 16287220
TI  - Diphosphonates: ocular risks.

PMID- 16287221
TI  - A transparent process.

PMID- 16287222
TI  - Retreat to make progress.

PMID- 16287223
TI  - The effects of first premolar extractions on third molar angulations.
AB  - The purpose of this study was to determine the relationship between the
      inclinations of second and third molars during a two- to 2.5-year period in
      patients treated orthodontically both with and without premolar extractions.
      Records of 37 first premolar extraction patients and 33 nonextraction patients
      were examined. The pretreatment and posttreatment panoramic radiographs were
      analyzed. The angles were measured between the long axis of the third molar and
      the occlusal plane and between the long axis of the third molar and the long axis
      of the second molar. Changes in third molar angulations from pretreatment to
      posttreatment for two groups were compared by Mann-Whitney U-test. Statistical
      analysis revealed that mandibular third molars showed an improvement in
      angulation relative to the occlusal plane in the first premolar extraction group.

PMID- 16287224
TI  - Understanding human biomonitoring.

PMID- 16287225
TI  - Lipid phase control of DNA delivery.
AB  - Cationic lipids form nanoscale complexes (lipoplexes) with polyanionic DNA and
      can be utilized to deliver DNA to cells for transfection. Here we report the
      correlation between delivery efficiency of these DNA carriers and the mesomorphic
      phases they form when interacting with anionic membrane lipids. Specifically,
      formulations that are particularly effective DNA carriers form phases of highest
      negative interfacial curvature when mixed with anionic lipids, whereas less
      effective formulations form phases of lower curvature. Structural evolution of
      the carrier lipid/DNA complexes upon interaction with cellular lipids is hence
      suggested as a controlling factor in lipid-mediated DNA delivery. A strategy for
      optimizing lipofection is deduced. The behavior of a highly effective lipoplex
      formulation, DOTAP/DOPE, is found to conform to this "efficiency formula".

PMID- 16287226
TI  - Polyketal nanoparticles: a new pH-sensitive biodegradable drug delivery vehicle.
AB  - In this report, we present an acid-sensitive drug delivery vehicle, termed
      polyketal nanoparticles, which are designed to target therapeutics to the acidic
      environments of tumors, inflammatory tissues, and phagosomes. The polyketal
      nanoparticles are formulated from poly(1,4-phenyleneacetone dimethylene ketal)
      (PPADK), a new hydrophobic polymer which contains ketal linkages in its backbone.
      The polyketal nanoparticles undergo acid-catalyzed hydrolysis into low molecular
      weight hydrophilic compounds and should therefore release encapsulated
      therapeutics at an accelerated rate in acidic environments. Importantly, the
      polyketal nanoparticles do not generate acidic degradation products after
      hydrolysis, as with polyester-based biomaterials. Dexamethasone-loaded
      nanoparticles, 200-600 nm in diameter, were fabricated with PPADK via an emulsion
      procedure using chloroform and water. The hydrolysis half-life of PPADK was
      measured to be 102 h at pH 7.4 and 35 h at pH 5.0. PPADK was synthesized by a new
      polymerization strategy based on the acetal exchange reaction. This new delivery
      system should find numerous applications in the field of drug delivery because of
      its ease of synthesis and excellent degradation properties.

PMID- 16287227
TI  - Magnetic resonance imaging of self-assembled biomaterial scaffolds.
AB  - Current interest in biomaterials for tissue engineering and drug delivery
      applications have spurred research into self-assembling peptide amphiphiles
      (PAs). Nanofiber networks formed from self-assembling PAs can be used as
      biomaterial scaffolds with the advantage of specificity by the incorporation of
      peptide-epitopes. Imaging the materials noninvasively will give information as to
      their fate in vivo. We report here the synthesis and in vitro MR images of self
      assembling peptide amphiphile contrast agents (PACAs) that form nanofibers. At
      400 MHz using a 0.1 mM Gd(III) conjugate of the PA we observed a T(1) three times
      that of a control gel. The PA derivative was doped into various epitope bearing
      PA solutions and upon gelling resulted in a homogeneous biomaterial as imaged by
      MRI.

PMID- 16287228
TI  - Transition from a normal to inverted cylinder for an amidine-bearing lipid/pDNA
      complex and its excellent transfection.
AB  - A cationic lipid (TRX) having an amidine headgroup was synthesized, and a
      lipoplex (i.e., plasmid DNA+lipid complex) was prepared from the mixture of TRX
      and two other neutral colipids. Small-angle X-ray scattering showed that the
      addition of DNA induced a structural transition from normal to inverted
      hexagonally packed cylinders. Transmission electron microscopy showed a
      threadlike micelle was transformed to a spherical micelle about 50-200 nm in
      diameter by adding DNA. A combination of these results leads to the conclusion
      that the complexed DNA is hexagonally packed (or condensed) into spherical
      aggregates. The size and morphology are believed suitable for endocytosis uptake
      or vesicle fusion. The complex made from pDNA (pEGFP-C1) and TRX was transfected
      to Hep G2. Flow cytometry and confocal microscopy showed that the present system
      expressed green fluorescence protein (GFP) more than a conventional transfection
      reagent. Additionally, TRX was less cytotoxic than other transfection reagents.
      This paper presents the attractive possibility of the amidine group for a
      transfection device.

PMID- 16287229
TI  - A site-specific bifunctional protein labeling system for affinity and fluorescent
      analysis.
AB  - Most covalent protein labeling schemes require a choice between visual and
      affinity properties, requiring the use of multiple fusion systems where both
      attributes are needed. While not disruptive at the single experiment level, this
      detail becomes critical when addressing high-throughput experimentation. Here we
      develop a uniform site-specific protein tag for use in both fluorescent and
      affinity screening. Covalent protein tagging with a stilbene reporter via
      promiscuous phosphopantetheinyltransferase (PPTase) modification enables a
      switchable, antibody-elicited fluorescent response in solution or on affinity
      resin. For demonstration purposes, VibB, a natural fusion protein harboring a
      carrier protein domain, was labeled with a stilbene tag through PPTase
      modification with a stilbene-labeled coenzyme A analogue. Analysis of the
      resulting stilbene-tagged VibB was accomplished by fluorescent and Western blot
      analysis with anti-stilbene monoclonal antibody EP2-19G2. The illustration of
      this method for general application to fusion protein analysis offers a dual role
      in assisting both solution-based fluorescent analysis and surface-based affinity
      detection and purification.

PMID- 16287230
TI  - Controlled recovery of the transcription of nanoparticle-bound DNA by
      intracellular concentrations of glutathione.
AB  - Positively charged trimethylammonium-functionalized mixed monolayer protected
      clusters (MMPCs) bind DNA through complementary electrostatic interactions,
      resulting in complete inhibition of DNA transcription of T7 RNA polymerase. DNA
      was released from the nanoparticle by intracellular concentrations of
      glutathione, resulting in efficient transcription. The restoration of RNA
      production was dose-dependent in terms of GSH, with considerable control of the
      release process possible through variation in monolayer structure. This work
      presents a new approach to controlled release of DNA, with potential applications
      in the creation of transfection vectors and gene regulation systems.

PMID- 16287231
TI  - A hydrophilic azobenzene-bearing amino acid for photochemical control of a
      restriction enzyme BamHI.
AB  - A novel hydrophilic and negatively charged azobenzene-bearing amino acid, 4'
      carboxyphenylazophenylalanine (azoAla 1), has been designed and synthesized for
      investigation of the photochemical regulation of the enzyme activity. The
      properties of photoisomerization and thermal stability of the cis-isomer were
      similar to those of a commonly used phenylazophenylalanine (azoAla 2). For
      photochemical control of the enzyme, these two azobenzene-bearing amino acids
      were incorporated into the specific position at the dimer interface of a
      restriction enzyme BamHI. These trans-azobenzene derivatives in the BamHI
      suppressed the enzymatic activity, and the following photoirradiation at 366 nm
      induced the recovery of its activity. Although the activities of both azoAla
      BamHI mutants were same level after a long time irradiation, the recovery of the
      activity of azoAla 1-BamHI was faster than that of azoAla 2-BamHI with a short
      time irradiation. This result suggests that the negatively charged carboxylate
      group introduced into an azobenzene moiety affects the behavior of azoAla in the
      protein scaffold during the trans-cis photoisomerization.

PMID- 16287232
TI  - Temperature sensitization of liposomes by use of thermosensitive block copolymers
      synthesized by living cationic polymerization: effect of copolymer chain length.
AB  - We prepared block copolymers of (2-ethoxy)ethoxyethyl vinyl ether (EOEOVE) and
      octadecyl vinyl ether (ODVE) with the number average molecular weights of 6900,
      9300, and 16 700 by living cationic polymerization. The poly(EOEOVE) block acts
      as a temperature-sensitive moiety, and the poly(ODVE) block acts as an anchor
      moiety. We also investigated the effect of chain length of the copolymer
      poly(EOEOVE) block on the ability to sensitize liposomes. The copolymers
      underwent a coil-globule transition at approximately 36 degrees C in the presence
      of a membrane of egg yolk phosphatidylcholine (EYPC), detected using differential
      scanning calorimetry (DSC). Liposomes encapsulating calcein, a water-soluble
      fluorescent dye, were prepared from mixtures of dioleoylphosphatidylethanolamine,
      EYPC, and the copolymers. While the copolymer-modified liposomes released little
      calcein below 30 degrees C, release was enhanced above 35 degrees C, indicating
      that dehydrated copolymer chains destabilized the liposome membrane. In addition,
      copolymers with a longer poly(EOEOVE) block induced a more drastic enhancement of
      contents release in a narrow temperature region near the transition temperature
      of the poly(EOEOVE) block. As a result, the copolymer with an average molecular
      weight of 16 700 generated highly sensitive liposomes that produced rapid and
      dramatic release of the contents in response to temperature.

PMID- 16287233
TI  - Structural characterization and buffering capacity in relation to the
      transfection efficiency of biodegradable polyurethane.
AB  - Inefficient release of polymer/DNA complexes from endocytic vesicles into the
      cytoplasm and the cytotoxic nature of cationic polymers are two of the primary
      causes of poor gene delivery. EG-polyurethane [poly(ethylene glycol)-PU, Poly 1],
      EGDM-polyurethane [poly(ethylene glycol), 2-(dimethylamino)ethylamine-PU, Poly
      2], and MDEADM-polyurethane [N-methyldiethanolamine, 2-(dimethylamino)ethylamine
      PU, Poly 3] were designed in this study to overcome these obstacles. The
      structural characteristics of polyurethanes and physicochemical properties of
      their formed complexes with DNA were determined to correlate their transfection
      efficiency. The results revealed that Poly 2 and Poly 3 could bind with plasmid
      DNA and yield positively charged complexes with a size required for transfection.
      Poly 3 showed the best in buffering capacity and its formed complexes with DNA
      could transfect COS-7 cells better than those of Poly 2 and Poly 1. This study
      reveals that the amine groups in the polymeric structure and the buffer capacity
      of a polymeric transfectant would affect its potential in DNA delivery. Also the
      size and binding properties of DNA and polymeric transfectants can be in
      correlation to the transfection efficiency of resulting DNA/polymer complexes.

PMID- 16287234
TI  - Fluorescent kabiramides: new probes to quantify actin in vitro and in vivo.
AB  - We present the design, synthesis, and biochemical and spectroscopic
      characterization of five functional fluorescent conjugates of kabiramide C
      (KabC), a small molecule biomimetic of gelsolin. The tetramethylrhodamine (TMR),
      rhodol green (RG), IC5, dapoxyl (DAP), and fluorescein diester (FDE) conjugates
      of KabC bind specifically to actin at the barbed end in a 1:1 complex. These
      probes are shown to function in an indistinguishable manner to the unmodified
      KabC. Various modalities of the fluorescence emission of these KabC probes,
      including fluorescence anisotropy and fluorescence resonance energy transfer, are
      used for the development of assays for the rapid determination of G-actin
      concentration in solution. The TMR-KabC and FDE-KabC probes are cell permeable
      and provide unique imaging information on the distribution and dynamics of actin
      filament within living cells.

PMID- 16287235
TI  - Biophysical and transfection studies of an amine-modified poly(vinyl alcohol) for
      gene delivery.
AB  - Novel, multifunctional polymers remain an attractive objective for drug delivery,
      especially for hydrophilic macromolecular drugs candidates such as peptides,
      proteins, RNA, and DNA. To facilitate intracellular delivery of DNA, new amine
      modified poly(vinyl alcohol)s (PVAs) were synthesized by a two-step process using
      carbonyl diimidazole activated diamines to produce PVAs with different degrees of
      amine substitution. The resulting polymers were characterized using NMR,
      thermogravimetric analysis (TGA), and gelpermation chromatography (GPC). Atomic
      force microscopy (AFM), dynamic light scattering photon correlation spectroscopy
      (PCS), and zeta-potential were used to investigate polyplexes of DNA with PVA
      copolymers. These studies suggest an influence of the polycation structure on the
      morphology of condensed DNA in polyplexes. Significant differences were observed
      by changing both the degrees of amine substitution and the structure of the PVA
      backbone, demonstrating that both electrostatic and hydrophobic interactions
      affect DNA condensation. DNA condensation measured by an ethidium bromide
      intercalation assay showed a higher degree of condensation with pDNA with
      increasing degrees of amine substitution and more hydrophobic functional groups.
      These findings are in line with transfection experiments, in which a good uptake
      of these polymer DNA complexes was noted, unfortunately, with little endosomal
      escape. Co-administration of chloroquine resulted in increased endosomal escape
      and higher transfection efficiencies, due to disruption of the endosomal
      membrane. In this study, the structural requirements for DNA complexation and
      condensation were characterized to provide a basis for rational design of
      nonviral gene delivery systems.

PMID- 16287236
TI  - Cell transduction pathways of transportans.
AB  - Attempts to unravel the cell translocation mechanism of a growing number of cell
      penetrating peptides (CPP) have revealed molecular determinants essential for
      internalization ability. The peptide sequence and the charge have been proposed
      to be the major factors in determining the membrane interaction mode and
      subsequent internalization pathway. Recent research in this field has shifted to
      search and design of novel CPPs with predefined vectorial properties and
      elucidation of the mechanism of cell entry of CPPs with high cargo delivery
      efficiency. Here we present a map of interaction modes with cell surface and
      intracellular traffic of transportan and its analogue TP10 complexed with
      fluorescently labeled avidin or streptavidin-gold conjugates. The protein cargo
      complexed with either peptide is transduced into HeLa and Bowes cells mostly in
      the endocytic vesicles with heterogeneous morphology and size as demonstrated by
      transmission electron microscopy (TEM) and confocal laser scanning fluorescence
      microscopy. Most of the induced vesicles are large, with 0.5-2 mum diameter,
      probably macropinosomes, but the complexes are present also in smaller vesicles,
      suggesting involvement of different pathways. Later the majority of complexes are
      translocated from the cell periphery into vesicles of perinuclear region and
      partly to lysosomes. A fraction of transportan-streptavidin complexes is present
      also freely in cytoplasm, both in the close vicinity of plasma membrane and more
      centrally, suggesting the escape from endosomal vesicles, since vesicles with
      discontinuous membrane were also detected by TEM. The cell-translocation process
      of transportan-protein complexes is temperature dependent and strongly inhibited
      at 8-10 degrees C and blocked at 4 degrees C when only interaction with the
      plasma membrane takes place.

PMID- 16287237
TI  - In vitro lipofection with novel asymmetric series of 1,2-dialkoylamidopropane
      based cytofectins containing single symmetric bis-(2-dimethylaminoethane) polar
      headgroups.
AB  - Novel N,N'-diacyl-1,2-diaminopropyl-3-carbamoyl[bis-(2-dimethylaminoethane)]
      bivalent cationic lipids were synthesized and evaluated for in vitro transfection
      activity against a murine melanoma cell line. In the absence of the helper lipid
      DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine), only the dioleoyl
      derivative 22 (1,2lb5) elicited transfection activity. The transfection activity
      of this lipid was reduced when formulated with DOPE. Contrary to that, the
      dimyristoyl derivative 19 (1,2lb2) mediated no activity when used alone but
      induced the highest levels of marker gene expression in the presence of DOPE. In
      an effort to correlate the transfection activity with cationic lipid structures,
      the physicochemical properties of cationic lipids in isolation and of lipoplexes
      were studied with surface tensiometry, photon correlation spectroscopy, gel
      electrophoresis mobility shift assay, and fluorescence techniques. In regard to
      the lipoplex properties, gel electrophoresis mobility shift assay and EtBr
      exclusion fluorescence assay revealed that the 1,2lb5 was the only lipid to
      associate and condense plasmid DNA, respectively. Photon correlation spectroscopy
      analysis found that 1,2lb5/DNA complexes were of relatively small size compared
      to all other lipoplexes. With respect to the properties of isolated lipids,
      Langmuir monolayer studies and fluorescence anisotropy on cationic lipid
      dispersions verified high two-plane elasticity and increased fluidity of the
      transfection competent dioleoyl derivative 1,2lb5, respectively. The results
      indicate that high transfection activity is mediated by cationic lipids
      characterized by an expanded mean molecular area, high molecular elasticity, and
      increased fluidity.

PMID- 16287238
TI  - Preparation and evaluation of thiol-modified gelatin nanoparticles for
      intracellular DNA delivery in response to glutathione.
AB  - To enhance the intracellular delivery potential of plasmid DNA using nonviral
      vectors, we have developed thiolated gelatin nanoparticles that can release the
      payload in the highly reducing environment, such as in response to glutathione.
      Thiolated gelatin was synthesized by covalent modification of the primary amino
      groups of Type B gelatin using 2-iminothiolane (Traut's reagent). The degree of
      thiolation of the polymers ranged from 0 to 43.71 mmol of reduced sulfhydryl (SH)
      groups when the amount of 2-iminothiolane was increased up to 100 mg per gram of
      the biopolymer. Cytotoxicity evaluations carried out by the formazan (MTS) assay
      showed that the thiolated gelatin prepared with 20 mg and 40 mg of 2
      iminothiolane (SHGel-20 and SHGel-40) per gram of gelatin had comparable cell
      viability profile to that of the unmodified gelatin. In vitro release studies of
      fluorescein isothiocyanate (FITC)-labeled dextran (mol wt. 70 000 Da), when
      encapsulated in gelatin and thiolated gelatin nanoparticles (150-250 nm in
      diameter), was found to be affected by the presence of glutathione (GSH) in the
      medium. The presence of GSH was found to enhance the release by about 40% in case
      of thiolated gelatin and about 20% in gelatin nanoparticles under similar
      conditions of temperature and GSH concentrations. Qualitative and quantitative
      analysis of transfection in NIH-3T3 murine fibroblast cells by the nanoparticles
      carrying plasmid DNA encoding for enhanced green fluorescent protein (EGFP-N1)
      was done by fluorescence confocal microscopy and fluorescence-activated cell
      sorting (FACS). Qualitative results showed highly efficient expression of GFP
      that remained stable for up to 96 h. Quantitative results from FACS showed that
      the thiolated gelatin nanoparticles (SHGel-20) were significantly more effective
      in transfecting NIH-3T3 cells than other carrier systems examined. The results of
      this study show that thiolated gelatin nanoparticles would serve as a
      biocompatible intracellular delivery system that can release the payload in a
      highly reducing environment.

PMID- 16287239
TI  - Near-infrared fluorescent RGD peptides for optical imaging of integrin
      alphavbeta3 expression in living mice.
AB  - Near-infrared fluorescence optical imaging is a powerful technique for studying
      diseases at the molecular level in preclinical models. We recently reported that
      monomeric RGD peptide c(RGDyK) conjugated to the NIR fluorescent dye specifically
      targets integrin receptor both in cell culture and in living subjects. In this
      report, Cy5.5-conjugated mono-, di-, and tetrameric RGD peptides were evaluated
      in a subcutaneous U87MG glioblastoma xenograft model in order to investigate the
      effect of multimerization of RGD peptide on integrin avidity and tumor targeting
      efficacy. The binding affinities of Cy5.5-conjugated RGD monomer, dimer, and
      tetramer for alpha(v)beta(3) integrin expressed on U87MG cell surface were
      determined to be 42.9 +/- 1.2, 27.5 +/- 1.2, and 12.1 +/- 1.3 nmol/L,
      respectively. All three peptide-dye conjugates had integrin specific uptake both
      in vitro and in vivo. The subcutaneous U87MG tumor can be clearly visualized with
      each of these three fluorescent probes. Among them, tetramer displayed highest
      tumor uptake and tumor-to-normal tissue ratio from 0.5 to 4 h postinjection.
      Tumor-to-normal tissue ratio for Cy5.5-conjugated RGD monomer, dimer, and
      tetramer were found to be 3.18 +/- 0.16, 2.98 +/- 0.05, and 3.63 +/- 0.09,
      respectively, at 4 h postinjection. These results suggest that Cy5.5-conjugated
      monomeric, dimeric, and tetrameric RGD peptides are all suitable for integrin
      expression imaging. The multmerization of RGD peptide results in moderate
      improvement of imaging characteristics of the tetramer, compared to that of the
      monomer and dimeric counterparts.

PMID- 16287240
TI  - Uptake of branched polypeptides with poly[L-lys] backbone by bone-marrow culture
      derived murine macrophages: the role of the class a scavenger receptor.
AB  - Selective delivery of antiparasitic or antibacterial drugs into infected
      macrophages could be a promising approach for improved therapies. Methotrexate
      conjugate with branched chain polypeptides exhibited pronounced anti-Leishmania
      activity in vitro and in vivo as reported here earlier. To identify structural
      requirements for efficient uptake of branched polypeptides, we have studied
      murine bone marrow culture-derived macrophages (BMMphi) from 129/ICR mice. We
      report on the translocation characteristics of structurally closely related
      compounds labeled with 5(6)-carboxyfluorescein. We found that this process is
      dependent on experimental conditions (e.g. polypeptide concentration, incubation
      time, and temperature). Using specific inhibitors as well as macrophages from
      wild-type and class-A scavenger receptor knockout (SR-A -/-) mice, we
      demonstrated that SR-A was involved in the endocytosis of some polypeptides
      depending on their charge. Uptake could be blocked by unlabeled polypeptide, by
      SR-A inhibitors, and by specific anti-SR-A monoclonal antibody. The polyanionic
      polypeptide poly[Lys(Succ-Glu(1.0)-dl-Ala(3.8))] (SuccEAK) with high charge
      density translocated more efficiently than poly[Lys(Ac-Glu(1.0)-dl-Ala(3.8))]
      (AcEAK), which had a lower anionic charge density. On the basis of experimental
      data presented, SuccEAK can be considered as a potential candidate for the design
      of a macromolecular carrier for specific drug delivery of bioactive entities into
      macrophages via SR-A.

PMID- 16287242
TI  - Tumor necrosis factor (TNF)-functionalized nanostructured particles for the
      stimulation of membrane TNF-specific cell responses.
AB  - Most members of the tumor necrosis factor (TNF) ligand family occur in both a
      membrane-bound and a soluble form, which can possess differential bioactivities.
      The aim of this work was the construction of a synthetic-biological hybrid system
      consisting of chemically nanostructured core-shell particles with a diameter of
      100 nm, 1 microm, or 10 microm and the cytokine TNF to obtain a tool that mimics
      the bioactivity of naturally occurring membrane-bound TNF. Synthetic core-shell
      nanoparticles consisting of an inorganic silica core and an ultrathin organic
      shell bearing a maleimide group at the shell surface which allowed for a covalent
      and site-directed coupling of CysHisTNF mutants were prepared. The TNF mutants
      were modified at the N-terminus by PCR cloning by introducing a His-Tag for
      purification and a free cysteine group for reaction with the particle-attached
      maleimide group. The resulting nanostructured hybrid particles initiated strong
      TNF receptor type 2 specific responses, otherwise only seen for the membrane
      bound form of TNF, but not the soluble cytokine, thus clearly demonstrating new
      and membrane TNF-like properties of the bioconjugated soluble TNF.

PMID- 16287241
TI  - Combined physical and chemical immobilization of glucose oxidase in alginate
      microspheres improves stability of encapsulation and activity.
AB  - Chemical sensors utilizing immobilized enzymes and proteins are important for
      monitoring chemical processes and biological systems. In this study, calcium
      cross-linked alginate hydrogel microspheres were fabricated as enzyme carriers by
      an emulsification technique. Glucose oxidase (GOx) was encapsulated in alginate
      microspheres using three different methods: physical entrapment (emulsion),
      chemical conjugation (conjugation), and a combination of physical entrapment and
      chemical conjugation (emulsion-conjugation). Nano-organized coatings were applied
      on alginate/GOx microspheres using the layer-by-layer self-assembly technique in
      order to stabilize the hydrogel/enzyme system under biological environment. The
      encapsulation of GOx and formation of nanofilm coating on alginate microspheres
      were verified with FTIR spectral analysis, zeta-potential analysis, and confocal
      laser scanning microscopy. To compare both the immobilization properties of
      enzyme encapsulation techniques and the influence of nanofilms with uncoated
      microspheres, the relationship between enzyme loading, release, and effective GOx
      activity (enzyme activity per unit protein loading) were studied over a period of
      four weeks. The results produced four key findings: (1) the emulsion-conjugation
      technique improved the stability of GOx in alginate microspheres compared to the
      emulsion technique, reducing the GOx leaching from microsphere from 50% to 17%;
      (2) the polyelectrolyte nanofilm coatings increased the GOx stability over time,
      but also reduced the effective GOx activity; (3) the effective GOx activity for
      the emulsion-conjugation technique (about 3.5 x 10(-)(5) AU microg(-)(1) s(-)(1))
      was higher than that for other methods, and did not change significantly over
      four weeks; and (4) the GOx concentration, when compared after one week for
      microspheres with three bilayers of poly(allylamine hydrochloride)/sodium
      poly(styrene sulfonate) ({PAH/PSS}) coating, was highest for the emulsion
      conjugation technique. As a result, the comparison of these three techniques
      showed the emulsion-conjugation technique to be a potentially effective and
      practical way to fabricate alginate/GOx microspheres for implantable glucose
      biosensor application.

PMID- 16287243
TI  - Preparation and characterization of a DOTA-lysine-biotin conjugate as an effector
      molecule for pretargeted radionuclide therapy.
AB  - Pretargeted radionuclide therapy depends on the establishment of a high
      concentration of secondary binding sites at a tumor to which low-molecular weight
      radiolabeled effector molecules can be directed. This study describes the simple
      synthesis of an effector molecule and its subsequent characterization to
      determine the extent to which it complied with the ideal requirements of such a
      compound. (Epsilon)-DOTA-(alpha)-biotinamidolysine (DLB) was synthesized in high
      yield and purity using conventional SPPS methodology. High radiochemical purities
      were obtained when labeled with several potentially useful radionuclides. The
      radiolabeled analogue bound to streptavidin efficiently with a stoichiometry
      similar to that of native biotin and showed high stability in serum and upon
      challenge with acid conditions. Biodistribution studies in normal animals showed
      a rapid rate of clearance from the blood and low retention of radioactivity by
      normal tissues. This design of effector molecule therefore shows promise for
      further pretargeted radionuclide therapy studies.

PMID- 16287244
TI  - Phosphoinositide-containing polymerized liposomes: stable membrane-mimetic
      vesicles for protein-lipid binding analysis.
AB  - Stable phosphoinositide (PIP(n))-containing liposomes were prepared using
      polydiacetylene photochemistry. Tethered pentacosadiynyl inositol polyphosphate
      (InsP(n)) analogues of Ins(1,3,4)P(3), Ins(1,4,5)P(3), and Ins(1,3,4,5)P(4) were
      synthesized, incorporated into vesicles made up of diyne-phosphatidylcholine and 
      phosphatidylethanolamine, and polymerized by UV irradiation. The polymerized
      liposome nanoparticles showed markedly increased stability over conventional
      PIP(n)-containing vesicles as a result of the covalent conjugated ene-yne network
      in the acyl chains. The polymerized liposomes were specifically recognized by
      PIP(n) binding PH domains in liposome overlay assays and amplified luminescent
      proximity homogeneous assays. Moreover, the biotin moiety allowed attachment of
      the nanoparticles to a streptavidin-coated sensor chips in surface plasmon
      resonance (SPR) sensor. The PIP(n) headgroups displayed on SPR sensors showed
      higher affinities for PH domains and PIP(n) monoclonal antibodies than did
      monomeric PIP(n)-analogues with biotinylated acyl chains.

PMID- 16287245
TI  - Fabrication and application of enzyme-incorporated peptide nanotubes.
AB  - Enzyme engineering is a fast-growing field in the pharmaceutical and food
      markets. For those applications, various substrates have been examined to
      immobilize and stabilize enzymes. In this report, we examined peptide nanotubes
      as supports for enzymes. When a model enzyme, Candida rugosa lipase, was
      encapsulated in peptide nanotubes, the catalytic activity of nanotube-bound
      lipases was increased 33% as compared to free-standing lipases at room
      temperature. At an elevated temperature, 65 degrees C, the activity of lipases
      inside the nanotubes was 70% higher than free-standing lipases. The activity
      enhancement of lipases in the peptide nanotubes is likely induced by the
      conformation change of lipases to the open form (the enzymatically active
      structure) as lipases are adsorbed on the inner surfaces of peptide nanotubes.

PMID- 16287246
TI  - Surface modification to reduce nonspecific binding of quantum dots in live cell
      assays.
AB  - Nonspecific binding is a frequently encountered problem with fluorescent labeling
      of tissue cultures when labeled with quantum dots. In these studies various cell
      lines were examined for nonspecific binding. Evidence suggests that nonspecific
      binding is related to cell type and may be significantly reduced by
      functionalizing quantum dots with poly(ethylene glycol) ligands (PEG). The length
      of PEG required to give a significant reduction in nonspecific binding may be as
      short as 12-14 ethylene glycol units.

PMID- 16287247
TI  - Synthesis and cellular studies of porphyrin-cobaltacarborane conjugates.
AB  - The total syntheses of five new porphyrin-cobaltacarborane conjugates (1-5) have
      been achieved in 88-98% yields in a single-step reaction between a nucleophilic
      meso-pyridyl-containing porphyrin and zwitterionic cobaltacarborane [3,3'-Co(8
      C(4)H(8)O(2)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))]. These unique zwitterionic
      compounds have one to four cobaltabisdicarbollide anions conjugated to the
      porphyrin macrocycle via (CH(2)CH(2)O)(2) chains. The X-ray structure of one of
      these conjugates (1) is presented and discussed. The cellular uptake,
      cytotoxicity, and subcellular localization of cobaltacarboraneporphyrins 1-5 were
      investigated in human HEp2 cells. The number and distribution of cobaltacarborane
      residues linked to the porphyrin macrocycle has a significant effect on the
      cellular uptake of the conjugates.

PMID- 16287248
TI  - Development and brain delivery of chitosan-PEG nanoparticles functionalized with
      the monoclonal antibody OX26.
AB  - The inhibition of the caspase-3 enzyme is reported to increase neuronal cell
      survival following cerebral ischemia. The peptide Z-DEVD-FMK is a specific
      caspase inhibitor, which significantly reduces vulnerability to the neuronal cell
      death. However, this molecule is unable to cross the blood-brain barrier (BBB)
      and to diffuse into the brain tissue. Thus, the development of an effective
      delivery system is needed to provide sufficient drug concentration into the brain
      to prevent cell death. Using the avidin (SA)-biotin (BIO) technology, we describe
      here the design of chitosan (CS) nanospheres conjugated with poly(ethylene
      glycol) (PEG) bearing the OX26 monoclonal antibody whose affinity for the
      transferrin receptor (TfR) may trigger receptor-mediated transport across the
      BBB. These functionalized CS-PEG-BIO-SA/OX26 nanoparticles (NPs) were
      characterized for their particle size, zeta potential, drug loading capacity, and
      release properties. Fluorescently labeled CS-PEG-BIO-SA/OX26 nanoparticles were
      administered systemically to mice in order to evaluate their efficacy for brain
      translocation. The results showed that an important amount of nanoparticles were
      located in the brain, outside of the intravascular compartment. These findings,
      which were also confirmed by electron microscopic examination of the brain tissue
      indicate that this novel targeted nanoparticulate drug delivery system was able
      to translocate into the brain tissue after iv administration. Consequently, these
      novel nanoparticles are promising carriers for the transport of the anticaspase
      peptide Z-DEVD-FMK into the brain.

PMID- 16287249
TI  - Synthesis and evaluation of hydrolyzable hyaluronan-tethered bupivacaine delivery
      systems.
AB  - Local anesthetics are useful for reducing acute pain, but their short duration
      precludes them from use in solely managing postoperative pain. To prolong the
      duration of local anesthesia, we conjugated bupivacaine to native hyaluronan (HA)
      and divinyl sulfone cross-linked Hylan A (Hylan B particles) using a hydrolyzable
      linker incorporating an imide. Bupivacaine was prepared for conjugation to HA by
      forming the acryl imide derivative. Separately, the carboxyl group of HA was
      reacted with nipsylethylamine (NEA) using carbodiimide-mediated coupling to
      provide HA-NEA that was subsequently reduced with tris(2-carboxyethylphosphine)
      hydrochloride to yield HA carrying a free sulfhydryl (HA-SH). The HA-bupivacaine
      conjugate was assembled by reacting HA-SH with acrylbupivacaine. Characterization
      of the conjugates showed 22% degree of modification by 1 mol of carboxyl. In
      vitro release studies comparing bupivacaine admixed in HA with bupivacaine
      conjugated to HA showed half-lives of 0.4 +/- 0.1 h, and 16.9 +/- 0.2 h,
      respectively, and the bupivacaine was released chemically unaltered as confirmed
      by LC-MS. In vivo studies to assess the duration of anesthetic activity were
      performed in a rat sciatic nerve blockade model. For these studies, bupivacaine
      was conjugated to Hylan B following a similar procedure, and the degree of
      modification obtained was 14%. Free bupivacaine (3 and 16 mg/kg) and free
      bupivacaine (3 mg/kg) admixed with Hylan B particles showed nerve block over 4,
      9, and 6 h, respectively. Free bupivacaine (3 mg/kg) admixed with bupivacaine (13
      mg/kg) conjugated to Hylan B particles showed a four to 5-fold longer impairment
      of motor function over the free bupivacaine formulations with a total block time
      of 19 h. Bupivacaine conjugated to Hylan B particles has the potential to prolong
      the duration of local anesthesia.

PMID- 16287250
TI  - SialylTn-mAb17-1A carbohydrate-protein conjugate vaccine: effect of coupling
      density and presentation of SialylTn.
AB  - Carbohydrate antigens resulting from aberrant glycosylation of tumor cells, such
      as SialylTn, represent attractive targets for cancer vaccination. However, T-cell
      independent carbohydrate antigens are poorly immunogenic and fail to induce
      memory and IgG class switch. Clustered expression patterns of some carbohydrates
      on the cell surface add further complexity to the design of carbohydrate-based
      vaccines. We describe here a vaccine consisting of SialylTn carbohydrate epitopes
      coupled to a highly immunogenic carrier molecule, mAb17-1A, adsorbed on
      alhydrogel and coformulated with a strong adjuvant, QS-21. The SialylTn-mAb17-1A
      conjugate vaccine was administered in Rhesus monkeys, and the immune responses
      against mAb17-1A, SialylTn, ovine submaxillary mucin, and tumor cells were
      analyzed. The data demonstrate that the density of carbohydrate epitopes on the
      carrier is an essential parameter for induction of anti-carbohydrate specific
      memory IgG immune responses. Furthermore, the influence of different types of
      presentation of SialylTn (monomeric vs trimers vs clustered via a branched
      polyethylenimine linker) on antibody titers and specificity was studied. High
      density coupling of SialylTn epitopes to mAb17-1A induced the strongest immune
      response against synthetic SialylTn and showed also the highest reactivity
      against natural targets, such as OSM and tumor cells.

PMID- 16287252
TI  - "Clickable" agarose for affinity chromatography.
AB  - Successful purification of biological molecules by affinity chromatography
      requires the attachment of desired ligands to biocompatible chromatographic
      supports. The Cu(I)-catalyzed cycloaddition of azides and alkynes-the premier
      example of "click chemistry"-is an efficient way to make covalent connections
      among diverse molecules and materials. Both azide and alkyne units are highly
      selective in their reactivity, being inert to most chemical functionalities and
      stable to wide ranges of solvent, temperature, and pH. We show that agarose beads
      bearing alkyne and azide groups can be easily made and are practical precursors
      to functionalized agarose materials for affinity chromatography.

PMID- 16287251
TI  - Novel thermosensitive 5-fluorouracil-cyclotriphosphazene conjugates: synthesis,
      thermosensitivity, degradability, and in vitro antitumor activity.
AB  - A novel thermosensitive macromolecular prodrug of 5-fluorouracil (5-FU) was
      synthesized using cyclotriphosphazene, and its thermosensitivity, degradability,
      and in vitro antitumor activity were studied. A series of alpha-substituted
      glycine derivatives of 5-FU containing carboxylic groups were prepared, and
      cyclotriphosphazenes with amino groups were synthesized via the stepwise
      substitution of hexachlorocyclotriphosphazene (NPCl(2))(3) with methoxy
      poly(ethylene glycol) (MPEG) or alkoxy ethylene oxide and lysine ethyl ester
      (LysOEt). The coupling reaction of the two derivatives, and their subsequent
      deprotection, yielded a thermosenstive 5-FU-cyclotriphosphazene conjugate, which
      exhibited a unique octopus-shaped molecular structure, in which the three
      hydrophilic PEG groups (or alkoxy ethylene oxides) were oriented in one
      direction, opposing the other three hydrophobic groups containing 5-FU, with
      respect to the trimer ring plane. This conjugate exhibited a reversible and
      thermosensitive phase transition in an aqueous medium, from soluble to insoluble
      states. The lower critical solution temperature (LCST) of the conjugate was
      controlled by substitution with different hydrophilic/hydrophobic side groups,
      and a few of the conjugates displayed LCSTs which were just below body
      temperature. This, of course, implies possible applications for local drug
      delivery by direct intratumoral injection. The conjugate exhibited gradual
      degradation at 37 degrees C in both neutral and acidic buffer solutions, and high
      temperature significantly facilitated its hydrolytic degradation. All of the
      conjugates displayed dose-dependent cytotoxicity against the leukemia L1210 cell
      line and exhibited more pronounced cytotoxic effects than did 5-FU.

PMID- 16287253
TI  - A peptide sequence controls the physical properties of nanoparticles formed by
      peptide-polymer conjugates that respond to a protein kinase a signal.
AB  - We previously reported that poly(N-isopropylacrylamide) grafted with Peptide 1 (
      GLRRASLG) and poly(ethylene glycol) changed its physical properties in response
      to an intracellular protein phosphorylation signal, protein kinase A (PKA)
      (Katayama, Y. et al. (2001) Macromolecules 34, 905). In this study, we
      investigated the effect of changing peptide structure on the lower critical
      solution temperature (LCST) of peptide-polymer conjugates, before and after
      phosphorylation with PKA. For Peptide 2 (Ac-LRRASL-), which has a formal net
      charge of +2 at physiological pH, the LCST of the conjugate decreased on
      phosphorylation. In contrast, the LCSTs of the conjugates with Peptide 3 (
      ALRRASLE) and Peptide 4 (Ac-DWDALRRASL-), which have neutral net charges, were
      greatly increased. This suggests that the LCST of the polymer was mainly governed
      by two factors: the change in hydration around the polymer chain and the
      interpeptide electrostatic repulsion, resulting from phosphorylation. These
      polymers have potential for use as drug capsules that respond to cellular
      conditions.

PMID- 16287254
TI  - Evaluation of ((4-hydroxyphenyl)ethyl)maleimide for site-specific
      radiobromination of anti-HER2 affibody.
AB  - Affibody molecules are a new class of small phage-display selected proteins using
      a scaffold domain of the bacterial receptor protein A. They can be selected for
      specific binding to a large variety of protein targets. An affibody molecule
      binding with high affinity to a tumor antigen HER2 was recently developed for
      radionuclide diagnostics and therapy in vivo. The use of the positron-emitting
      nuclide (76)Br (T(1/2) = 16.2 h) could improve the sensitivity of detection of
      HER2-expressing tumors. A site-specific radiobromination of a cysteine-containing
      variant of the anti-HER2 affibody, (Z(HER2:4))(2)-Cys, using ((4
      hydroxyphenyl)ethyl)maleimide (HPEM), was evaluated in this study. It was found
      that HPEM can be radiobrominated with an efficiency of 83 +/- 0.4% and thereafter
      coupled to freshly reduced affibody with a yield of 65.3 +/- 3.9%. A "one-pot"
      labeling enabled the radiochemical purity of the conjugate to exceed 97%. The
      label was stable against challenge with large excess of nonlabeled bromide and in
      a high molar strength solution. In vitro cell tests demonstrated that
      radiobrominated affibody binds specifically to the HER2-expressing cell-line, SK
      OV-3. Biodistribution studies in nude mice bearing SK-OV-3 xenografts have shown
      tumor accumulation of 4.8 +/- 2.2% IA/g and good tumor-to-normal tissue ratios.

PMID- 16287255
TI  - Hydrophobic transmembrane-peptide lipid conjugations enhance membrane binding and
      functional activity in T-cells.
AB  - Application of different delivery methods for therapeutic peptides has gained
      much attention in recent years. In this paper we conjugated a transmembrane
      hydrophobic peptide (core peptide; CP) derived from the T-cell antigen receptor
      alpha-chain sequence with either one (LP1), two (LP2), or three (LP3) palmitic
      acids through a Tris linkage. The effect of these lipopeptides (LPs) were
      compared to CP's activity both in vitro and in model membrane binding experiments
      using surface plasmon resonance. The influence of charged amino acids, arginine
      and lysine, within the CP sequence was examined by synthesizing analogues where
      arginine and lysine were replaced by the neutral amino acid alanine and these
      analogues were subsequently Tris-lipid conjugated with either one (XP1), two
      (XP2), or three (XP3) palmitic acids through a Tris linkage. The results
      indicated that the amount of irreversible binding for LPs were all greater than
      that of the underivatized CP in model membranes. None of the LPs could be
      dissociated from the liposome membranes, even after prolonged washing. Binding
      results for the neutral conjugates showed that only the XP1 bound to model
      membranes. This binding was 20% as efficient compared to LP1. In biological
      assays it was found that LP1 and XP1 were toxic to cells. LP3 inhibited IL-2
      production more effectively than CP. Control lipopeptides (XP2, XP3) did not
      inhibit IL-2 production. These results demonstrate that the number of lipids
      conjugated to peptide, and the charged amino acids of CP, are both essential
      factors for peptide function and activity that can be enhanced by lipidation.

PMID- 16287256
TI  - 2,2-Bis(ethoxycarbonyl)- and 2-(alkylaminocarbonyl)-2-cyano-substituted 3
      (pivaloyloxy)propyl groups as biodegradable phosphate protections of
      oligonucleotides.
AB  - Oligonucleotides bearing biodegradable phosphate protecting groups have been
      synthesized on a solid support. For this purpose, two dimeric building blocks,
      viz. 5'-O-(4,4'-dimethoxytrityl)-(R(P),S(P))-O(P)-[2,2-bis(ethoxycarbonyl)-3
      (pivaloyloxy)propyl]-P-thiothymidylyl-(3',5')-thymidine 3'-[O-(2-cyanoethyl)-N,N
      diisopropylphosphoramidite] (1) and 5'-O-(4,4'-dimethoxytrityl)-(R(P),S(P))-O(P)
      [2-cyano-2-(2-phenylethylaminocarbonyl)-3-(pivaloyloxy)propyl]thymidylyl-(3',5')
      thymidine 3'-(H-phosphonate) (2), were prepared. Phosphoramidite 1 was
      incorporated into an phosphorothioate oligothymidylate sequence on a base-labile
      hydroquinone-O,O'-diacetic acid linker (Q-linker) and on a photolabile 4-alkoxy-5
      methoxy-2-nitrobenzyl carbonate linker (11). H-Phosphonate 2 was, in turn,
      incorporated into an oligothymidylate sequence only on the photolabile linker.
      Kinetics of the removal of the protecting groups by porcine liver esterase and
      subsequent retro aldol condensation/phosphate elimination were then studied.
      While the pro-oligonucleotide that contained only one phosphate protection gave
      the deprotected phosphorothioate oligonucleotide in a quantitative yield, the
      enzymatic step was markedly decelerated upon increasing the number of protection
      groups, and hence chain cleavage started to compete.

PMID- 16287257
TI  - Accelerated bioorthogonal conjugation: a practical method for the ligation of
      diverse functional molecules to a polyvalent virus scaffold.
AB  - Covalent bond formation to proteins is made difficult by their multiple
      unprotected functional groups and normally low concentrations. A water-soluble
      sulfonated bathophenanthroline ligand (2) was used to promote a highly efficient
      Cu(I)-mediated azide-alkyne cycloaddition (CuAAC) reaction for the chemoselective
      attachment of biologically relevant molecules to cowpea mosaic virus (CPMV). The
      ligated substrates included complex sugars, peptides, poly(ethylene oxide)
      polymers, and the iron carrier protein transferrin, with routine success even for
      cases that were previously resistant to azide-alkyne coupling using the
      conventional ligand tris(triazolyl)amine (1). The use of 4-6 equiv of substrate
      was sufficient to achieve loadings of 60-115 molecules/virion in yields of 60
      85%. Although it is sensitive to oxygen, the reliably efficient performance of
      the Cu.2 system makes it a useful tool for demanding bioconjugation applications.

PMID- 16287258
TI  - Effect of coligands on biodistribution characteristics of ternary ligand 99mTc
      complexes of a HYNIC-conjugated cyclic RGDfK dimer.
AB  - This report describes biodistribution characteristics of three ternary ligand
      complexes [(99m)Tc(SQ168)(tricine)(L)] (SQ168 = [2-[[[5-[carboonyl]-2
      pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{Lys-Arg-Gly-Asp-d
      Phe})-cyclo{Lys-Arg-Gly-Asp-d-Phe}; L = TPPTS (trisodium triphenylphosphine
      3,3',3' '-trisulfonate), ISONIC (isonicotinic acid) and PDA (2,5
      pyridinedicarboxylic acid)) in athymic nude mice bearing MDA-MB-435 human breast
      cancer xenografts. Ternary ligand complexes [(99m)Tc(SQ168)(tricine)(L)] (L =
      TPPTS, ISONIC and PDA) were prepared and were analyzed by a reversed HPLC method.
      Surprisingly, coligands have little impact on log P values of their ternary
      ligand (99m)Tc complexes even though HPLC retention times suggest that
      [(99m)Tc(SQ168)(tricine)(PDA)] and [(99m)Tc(SQ168)(tricine)(ISONIC)] are more
      hydrophilic than [(99m)Tc(SQ168)(tricine)(TPPTS)]. The results from
      biodistribution studies indicated that excretion kinetics of the (99m)Tc-labeled
      cyclic RGDfK dimer can be modified by the choice of coligand. The fact that all
      three radiotracers show high tumor uptake during the 2 h study period suggests
      that the coligand has minimal effect on the tumor targeting capability of the
      (99m)Tc-labeled cyclic RGDfK dimer. Results from the blocking experiment suggest
      that the tumor localization of the (99m)Tc-labeled cyclic RGDfK dimer is integrin
      alpha(v)beta(3)-mediated. On the basis of their liver uptake and tumor/liver
      ratios, we believe that PDA has the advantage over TPPTS and ISONIC for the
      (99m)Tc-labeling of HYNIC-biomolecule conjugates.

PMID- 16287259
TI  - Hemostatic effects of phospholipid vesicles carrying fibrinogen gamma chain
      dodecapeptide in vitro and in vivo.
AB  - We studied prototypes of platelet substitutes that bear on their surface a
      dodecapeptide, HHLGGAKQAGDV (H12). The peptide is a fibrinogen gamma chain
      carboxy-terminal sequence (gamma400-411) and recognizes specifically the active
      form of glycoprotein (GP) IIb/IIIa on the surface of activated platelets. We
      conjugated H12 to the end of poly(ethylene glycol) chains on the surface of a
      phospholipid vesicle with an average diameter of 220 nm to prepare H12-PEG
      vesicles. The half-life of the H12-PEG-vesicles was significantly prolonged by
      PEG modification, and the ability of H12 on the surface of the vesicle to
      recognize GPIIb/IIIa was maintained even though the surface was modified with PEG
      chains. The H12-PEG-veiscles enhanced the in vitro thrombus formation of
      platelets that were adhering to a collagen-immobilized plate, when
      thrombocytopenia-imitation blood was passed over the plate. Based on the flow
      cytometric analyses of PAC-1 binding and P-selectin expression, the H12-PEG
      vesicles were shown not to cause platelet activation. Furthermore, the H12-PEG
      vesicles dose-dependently shortened the tail bleeding time of thrombocytopenic
      rats. It was confirmed that the H12-PEG-vesicles had a hemostatic effect and may
      be a suitable candidate for an alternative to human platelet concentrates
      transfused into thrombocytopenic patients.

PMID- 16287260
TI  - Carbohydrate-bearing 3-hydroxy-4-pyridinonato complexes of gallium(III) and
      indium(III).
AB  - Gallium and indium complexes with pendant carbohydrates have been prepared and
      examined for their potential as radiopharmaceuticals. Carbohydrate-bearing 3
      hydroxy-4-pyridinone ligand precursors and their tris(ligand)gallium(III) and 
      indium(III) complexes were synthesized and characterized by mass spectrometry,
      elemental analysis, and (1)H and (13)C NMR spectroscopy, and in the case of one
      intermediate, by X-ray crystallography. With three equivalents of ligand, neutral
      complexes formed with the bidentate hydroxypyridinone moiety complexing the
      gallium(III) and indium(III) metal centers.

PMID- 16287261
TI  - In vitro system to estimate renal brush border enzyme-mediated cleavage of
      Peptide linkages for designing radiolabeled antibody fragments of low renal
      radioactivity levels.
AB  - Renal localization of radiolabeled antibody fragments presents a problem in
      targeted imaging and radiotherapy. We recently reported that Fab fragments
      labeled with 3'-[(131)I]iodohippuryl N(epsilon)-maleoyl-l-lysine (HML)
      demonstrated markedly low renal radioactivity levels from early postinjection in
      mice. Previous studies suggested that low renal radioactivity levels were
      attributable to cleavage of the glycyl-lysine sequence in HML by the action of
      renal brush border enzymes, followed by urinary excretion of the resulting m
      iodohippuric acid. In this study, an in vitro system using brush border membrane
      vesicles (BBMVs) isolated from the rat kidney cortex was developed to estimate
      renal brush border enzyme(s)-mediated cleavage of the peptide linkage. Low
      molecular weight HML derivatives, 3'-[(125)I]iodohippuryl l-lysine (HL), 3'
      [(125)I]iodohippuryl N(epsilon)-tert-butoxycarbonyl-l-lysine (HBL), and their d
      amino acid counterparts, were synthesized and incubated in BBMVs. Both [(125)I]HL
      and [(125)I]HBL generated m-[(125)I]iodohippuric acid after incubation in BBMVs
      at 37 degrees C while the latter liberated significantly higher amounts of the
      metabolite. [(125)I]d-HL and [(125)I]d-HBL failed to release the metabolite under
      similar conditions. The liberation of m-[(125)I]iodohippric acid from [(125)I]HL
      was significantly facilitated or completely inhibited by the addition of an
      activator or an inhibitor for carboxypeptidase M. The release of m
      [(125)I]iodohippuric acid from [(125)I]HBL increased by the addition of the
      activator, whereas the inhibitor partially inhibited the release of the
      metabolite from [(125)I]HBL. The BBMV-mediated release of m-[(125)I]iodohippuric
      acid from [(125)I]HBL was not impaired by the addition of inhibitors for neutral
      endopeptidase or renal dipeptidase. These findings showed that the glycyl-l
      lysine sequence in HML would be recognized and cleaved by metalloenzymes and
      nonmetalloenzymes on the renal brush border even when iodine was incorporated
      into a benzene ring and the N(epsilon)-amine residue of lysine was chemically
      modified, which supported the hypothesis that low renal radioactivity levels of
      HML-conjugated Fab fragments would be attributed to the release of m-iodohippuric
      acid by renal brush border enzymes. This study suggested that this in vitro
      system using BBMVs would be useful to estimate radiolabeling reagents of antibody
      fragments or peptides designed to reduce renal radioactivity with a variety of
      radionuclides.

PMID- 16287262
TI  - Site-specific cross-linking of proteins through tyrosine hexahistidine tags.
AB  - The genetic addition of hexahistidine (H(6)) tags is widely used to isolate
      recombinant proteins by immobilized metal-affinity chromatography (IMAC).
      Addition of a tyrosine residue to H(6) tags enabled proteins to be covalently
      cross-linked under mild conditions in a manner similar to the natural, site
      specific cross-linking of tyrosines into dityrosine. A series of seven
      hexahistidine tags with tyrosines placed in various positions (H(6)Y tags) were
      added to the amino terminus of the I28 immunoglobulin domain of the human cardiac
      titin. The H(6)Y-tagged I28 dimerized in the presence of excess Ni(2+) with a
      K(D) of 200 microM. Treatment of Ni(2+)-dimerized H(6)Y-I28 with an oxidant,
      monoperoxyphthalic acid (MMPP) or sodium sulfite, resulted in covalent protein
      multimerization through chelated Ni(2+)-catalyzed cross-linking of the Y residues
      engineered into the H(6) tag. The protein oligomerization was observed by sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE). The presence of
      dityrosine in the cross-linked proteins was confirmed by fluorescence emission at
      410 nm. Proteins lacking the Y residue in the H(6) tag treated with the same
      oxidative conditions did not cross-link or exhibit dityrosine fluorescence,
      despite the presence of an endogenous Y residue. The method may have potential
      uses in other protein conjugation applications such as protein labeling and
      interfacial immobilization of proteins on artificial surfaces.

PMID- 16287263
TI  - Synthesis of chemical probes to map sulfenic acid modifications on proteins.
AB  - Cysteine sulfenic acids in proteins can be identified by their ability to form
      adducts with dimedone, but this reagent imparts no spectral or affinity tag for
      subsequent analyses of such tagged proteins. Given its similar reactivity toward
      cysteine sulfenic acids, 1,3-cyclohexadione was synthetically modified to an
      alcohol derivative and linked to fluorophores based on isatoic acid and 7
      methoxycoumarin. The resulting compounds retain full reactivity and specificity
      toward cysteine sulfenic acids in proteins, allowing for incorporation of the
      fluorescent label into the protein and "tagging" it based on its sulfenic acid
      redox state. Control experiments using dimedone further show the specificity of
      the reaction of 1,3-diones with protein sulfenic acids in aqueous media. These
      new compounds provide the basis for an improved method for the detection of
      protein sulfenic acids.

PMID- 16287264
TI  - An electrochemical color-switchable RGB dye: tristable [2]catenane.
AB  - We propose a design for an electrochemically driven RGB dye based on a tristable
      [2]catenane, in which the color of the molecule can be switched between Red,
      Green, and Blue by merely changing voltage. Based on DFT calculations, we
      conclude that the tristable [2]catenane should consist of a CBPQT4+ ring
      interlocked with a polyether macrocyle containing DNP (red), TTF (green), and
      FBZD (blue) units as the tunable RGB color-generating donors. Thus, at
      controllable voltages 0, V1, and V2, the [2]catenane is expected to display
      green, blue, and red colors, respectively. The advent of these RGB tristable
      molecules may have potential applications in low cost paperlike electronic
      displays.

PMID- 16287265
TI  - Perfectly dissolved boron nitride nanotubes due to polymer wrapping.
AB  - We report for the first time that boron nitride nanotubes (BNNTs) may be
      dissolved in organic solvents by wrapping them with a polymer. Transmission
      electron microscopy and cathodoluminescence studies indicate the strong pi-pi
      interactions between BNNTs and the polymer. A band gap ranging from 5.2 to 5.5 eV
      was documented for the BNNTs independent of their geometrical characteristics by
      using ultraviolet-visible absorption experiments on composite films and thin BNNT
      films prepared from solutions.

PMID- 16287267
TI  - Efficient primer strand extension beyond oxadiazole carboxamide nucleobases.
AB  - Two oxadiazole carboxamide deoxyribonucleoside analogues are described that can
      be incorporated and efficiently extended by Taq DNA polymerase. The primer strand
      extension beyond oxadiazole nucleoside analogues occurs at rates similar to the
      values observed for the canonical Watson-Crick base pairs irrespective of the
      template nucleobase. These distinctive chemical effects in DNA polymerase
      extensions are attributed to the smaller size and unique electronic properties of
      the oxadiazole nucleobase.

PMID- 16287266
TI  - Ruthenium-catalyzed cycloaddition of alkynes and organic azides.
AB  - Cp*RuCl(PPh3)2 is an effective catalyst for the regioselective "fusion" of
      organic azides and terminal alkynes, producing 1,5-disubstituted 1,2,3-triazoles.
      Internal alkynes also participate in this catalysis, resulting in fully
      substituted 1,2,3-triazoles.

PMID- 16287268
TI  - Room-temperature Wurtzite ZnS nanocrystal growth on Zn finger-like peptide
      nanotubes by controlling their unfolding peptide structures.
AB  - ZnS nanocrystal, a class of wide-gap semiconductors, has shown interesting
      optical, electrical, and optoelectric properties via quantum confinement. For
      those applications, phase controls of ZnS nanocrystals and nanowires were
      critical to tune their physical properties to the appropriate ones. The wurtzite
      ZnS nanocrystal growth at room temperature is the useful fabrication; however,
      the most stable ZnS structure in nanoscale is the zinc blende (cubic) structure,
      and scientists have just begun exploring the room-temperature synthesis of the
      wurtzite (hexagonal) structure of ZnS nanocrystals. In this report, we applied
      the Zn finger-like peptides as templates to control the phase of ZnS nanocrystals
      to the wurtzite structure at room temperature. The peptide nanotubes, consisting
      of a 20 amino acids (VAL-CYS-ALA-THR-CYS-GLU-GLN-ILE-ALA-ASP-SER-GLN-HIS-ARG-SER
      HIS-ARG-GLN-MET-VAL, M1 peptide) synthesized based on the peptide motif of the
      Influenza Virus Matrix Protein M1, could grow the wurtzite ZnS nanocrystals on
      the nanotube templates in solution. In the M1 protein, the unfolding process of
      the helical peptide motif via pH change creates a linker region between N- and C
      terminated helical domains that contains a Zn finger-like Cys2His2 motif. Because
      the higher pH increases the uptake of Zn ions in the Cys2His2 motif of the M1
      peptide by unfolding more helical domains, the pH change can essentially control
      the size and the number of the nucleation sites in the M1 peptides to grow ZnS
      nanocrystals with desired phases. Here we optimized the nucleation sites in the
      M1 peptides by unfolding them via pH change to obtain highly monodisperse and
      crystalline wurtzite ZnS nanocrystals on the template nanotubes at room
      temperature. This type of peptide-induced biomineralization technique will
      provide a clean and reproducible method to produce semiconductor nanotubes due to
      its efficient nanocrystal formation, and the band gaps of resulting nanotubes can
      also be tuned simply by phase control of ZnS nanocrystal coatings via the
      optimization of the unfolding peptide structures.

PMID- 16287269
TI  - Iron substitution for sodium in a carboxylate-bridged, heterodinuclear sodium
      iron complex.
AB  - The synthesis and structural characterization of the carboxylate-bridged,
      heterodinuclear iron-sodium complex [NaFe(PIC2DET)(mu-O2CTrp)3] (2), where
      PIC2DET (1) is a 2,3-diethynyltriptycene-linked dipicolinic methyl ester ligand
      and Trp is 9-triptycenyl, are described. The metal ions in 2 are bridged by three
      triptycene carboxylates with an Fe...Na distance of 3.181(2) A, and each is
      coordinated to a pyridine nitrogen and carbonyl oxygen atom of 1, forming two
      five-membered chelate rings. A linkage isomer in which Fe1 is bound by the other
      ester oxygen atom of 1 was identified by X-ray crystallographic analysis.
      Treatment of 2 with Fe(OTf)2.2MeCN resulted in substitution of sodium by iron(II)
      to give the cationic diiron(II) complex [Fe2(PIC2DET)(mu-O2CTrp)3][OTf] (3). This
      reaction was investigated by UV-vis, IR, MS, and stopped-flow spectroscopy. The
      substitution is first order with respect to 2 and zero order with respect to
      Fe(OTf)2.2MeCN (kobs = 21 +/- 2 s-1), consistent with a dissociative mechanism. A
      positive enthalpy of activation (DeltaH = 59 +/- 6 kJ mol-1) and negative entropy
      of activation (DeltaS = -20 +/- 6 J mol-1 K-1) were calculated from the
      temperature dependence of the rate-determining dissociation step.

PMID- 16287270
TI  - Tailoring of nanoscale porosity in carbide-derived carbons for hydrogen storage.
AB  - The poor performance of hydrogen storage materials continues to hinder
      development of fuel cell-powered automobiles. Nanoscale carbons, in particular
      (activated carbon, exfoliated graphite, fullerenes, nanotubes, nanofibers, and
      nanohorns), have not fulfilled their initial promise. Here we show that carbon
      materials can be rationally designed for H2 storage. Carbide-derived carbons
      (CDC), a largely unknown class of porous carbons, are produced by high
      temperature chlorination of carbides. Metals and metalloids are removed as
      chlorides, leaving behind a collapsed noncrystalline carbon with up to 80% open
      pore volume. The detailed nature of the porosity-average size and size
      distribution, shape, and total specific surface area (SSA)-can be tuned with high
      sensitivity by selection of precursor carbide (composition, lattice type) and
      chlorination temperature. The optimum temperature is bounded from below by
      thermodynamics and kinetics of chlorination reactions and from above by
      graphitization, which decreases SSA and introduces H2-sorbing surfaces with
      binding energies too low to be useful. Intuitively, pores of different size and
      shape should not contribute equally to hydrogen storage. By correlating pore
      properties with 77 K H2 isotherms from a wide variety of CDCs, we experimentally
      confirm that gravimetric hydrogen storage capacity normalized to total pore
      volume is optimized in materials with primarily micropores ( approximately 1 nm)
      rather than mesopores. Thus, in agreement with theoretical predictions, a narrow
      size distribution of small pores is desirable for storing hydrogen, while large
      pores merely degrade the volumetric storage capacity.

PMID- 16287271
TI  - Oriented immobilization of Desulfovibrio gigas hydrogenase onto carbon electrodes
      by covalent bonds for nonmediated oxidation of H2.
AB  - The orientation of hydrogenase bound covalently to a pyrolytic graphite edge
      electrode modified with a 4-aminophenyl monolayer can be modulated via
      electrostatic interactions during the immobilization step. At low ionic strength
      and when the amino groups of the electrode surface are mostly protonated, the
      hydrogenase is immobilized with the negatively charged region that surrounds its
      4Fe4S cluster nearer to the protein surface facing the electrode. This allows
      direct electron transfer between the immobilized hydrogenase and the electrode,
      which is observed by the strong catalytic currents measured in the presence of
      the H2 substrate. Therefore, a very stable enzymatic electrode is produced that
      catalyzes nonmediated H2 oxidation.

PMID- 16287272
TI  - Electronic dissymmetry in chiral recognition.
AB  - The pi-bonding of the beta-diketonate ligands in C2-symmetric (dike)2TiX2
      complexes engenders a significant electronic dissymmetry, with the LUMO of the
      complex resembling a "tipped" dz2 orbital whose tilt with respect to the plane
      containing the metal and the two X groups is determined by the configuration at
      titanium. The ability of this electronic dissymmetry to promote chiral
      recognition has been probed in 1,1'-bi-2-naphtholate complexes
      (RCOCHCOR)2Ti(BINOL) (R = CH3, Ph, or tBu). The complexes show exclusively one
      diastereomer by NMR, which has been established as the one predicted on
      electronic grounds by crystallography of the dibenzoylmethane and 2,2,6,6
      tetramethylheptanedione complexes. Confirmation that the selectivity is due to
      electronic rather than steric factors is given by the behavior of the tin
      analogues, which are structurally similar but show much smaller
      diastereoselectivities.

PMID- 16287273
TI  - Characterization of a diferrous terminal hydride mechanistically relevant to the
      Fe-only hydrogenases.
AB  - Reduction of diferrous dithiolato complexes with hydride donor reagents affords
      the first example of the previously elusive terminal diferrous hydride,
      [Fe2(edt)(mu-CO)(H)(CO)(PMe3)4]PF6 (edt = S2C2H4). Crystallographic
      characterization shows that this model contains an asymmetrical semi-bridging CO
      trans to a terminal hydrido, as indicated in the Hred state in the D.
      desulfuricans enzyme. The model reacts with protons to yield H2 and rearranges
      via an intramolecular process to the isomeric mu-hydrido isomer, which is
      unreactive toward protons.

PMID- 16287274
TI  - Enantiospecific Sn(II)- and Sn(IV)-catalyzed cycloadditions of aldehydes and
      donor-acceptor cyclopropanes.
AB  - A cycloaddition strategy for the synthesis of highly enantioenriched 2,5-cis
      disubstituted tetrahydrofurans has been developed. In the presence of catalytic
      Sn(OTf)2 or SnCl4, a range of aldehydes will undergo formal [3 + 2]
      cycloadditions with a scalemic donor-acceptor cyclopropane to form optically
      active heterocycles. Mechanistic studies support an unusual SN2 attack by the
      aldehyde on the activated cyclopropane. Through this mechanism, stereochemical
      information contained in the cyclopropane is effectively transferred to the
      tetrahydrofuran products.

PMID- 16287275
TI  - Intermolecular C-H bond activation promoted by a titanium alkylidyne.
AB  - The transient titanium alkylidyne complex (PNP)TiCtBu (PNP = N-[2-P(CHMe2)2-4
      methylphenyl]2-), prepared from alpha-hydrogen abstraction of the corresponding
      alkylidene-alkyl species (PNP)Ti=CHtBu(CH2tBu), can readily undergo
      intermolecular 1,2-addition of C-H bonds of benzene and SiMe4. Synthesis and
      reactivity, isotopic labeling, kinetics, and theoretical studies strongly favor
      an alkylidyne pathway and the alpha-H abstraction step to be the rate-determining
      step.

PMID- 16287276
TI  - Identification by 15N refocused INADEQUATE MAS NMR of intermolecular hydrogen
      bonding that directs the self-assembly of modified DNA bases.
AB  - 15N solid-state NMR refocused INADEQUATE spectra of two lipophilic deoxyguanosine
      derivatives unambiguously identify different intermolecular hydrogen-bonding
      arrangements that are indicative of either guanine ribbon or quartet self
      assembly. The observation of guanine quartet formation in the absence of metal
      ions is a further example that challenges the accepted dogma that quartet
      formation requires metal ions.

PMID- 16287277
TI  - Synthesis of single-crystalline CoP nanowires by a one-pot metal-organic route.
AB  - A simple one-pot method has been used to prepare uniform single-crystalline CoP
      nanowires with a high aspect ratio by the thermal-decomposition reaction of
      cobalt(II) acetylacetone with long-chain alkylphosphonic acid in the presence of
      hexadecylamine (HDA) and trioctylphosphine oxide (TOPO) at high temperature. The
      crystal morphology of the resulting nanowires can be influenced by the ratio of
      HDA and TOPO.

PMID- 16287278
TI  - Conducting polymer electrochemical switching as an easy means for designing
      active plasmonic devices.
AB  - Due to the continuously increasing demand for ultimate miniaturization of
      electronic and photonic systems, molecular electronics and plasmonic devices are
      currently booming as alternative technologies because of their very promising
      potential in writing, reading, storing, and processing information at the
      nanoscale. Conducting polymers or oligomers have been proposed and used as basic
      building blocks in molecular and plastic electronics since the end of the 80s.
      Plasmonics is, on the other hand, an emerging branch of photonics which uses
      nanostructured materials that support surface plasmons. Among plasmonic devices,
      active plasmonic devices are still lacking. In this work, we report on new active
      molecular plasmonic devices in which the electrochemical switching of a
      nanometric film of conductive polymer between its reduced and oxidized state is
      used in order to control, switch, and modulate localized surface plasmon (LSP)
      resonance of gold nanoparticle arrays.

PMID- 16287279
TI  - High symmetric 18-facet polyhedron nanocrystals of Cu7S4 with a hollow nanocage.
AB  - On the basis of Kirkendall Effect, high symmetric 18-facet polyhedral
      nanocrystals of Cu7S4 with a hollow nanocage could be converted from cubic
      nanocrystals of Cu2O in an aqueous media. The presence of organic additives makes
      the surface energy of {110} smaller than those of {100} and {111}. The growth of
      nanocrystals along the normal direction of highest energy surface {100} leads to
      the formation of a 18-facet polyhedron.

PMID- 16287280
TI  - Modeling errors in NOE data with a log-normal distribution improves the quality
      of NMR structures.
AB  - The distribution of the deviation of calculated from measured nuclear Overhauser
      effect (NOE) intensities is a priori unknown. The use of a log-normal
      distribution to describe these deviations permits the direct calculation of a
      structure from the measured intensities without first converting them into
      distance bounds. We show that the log-normal distribution is a natural choice for
      describing errors in NOE data and that it improves the accuracy, precision, and
      quality of the calculated structures compared to the usual bounds representation.

PMID- 16287281
TI  - Cysteine-derived organocatalyst in a highly enantioselective intramolecular
      Michael reaction.
AB  - Asymmetric intramolecular Michael reaction catalyzed by an organocatalyst derived
      from cysteine has been developed for the synthesis of chiral bicyclo[4.3.0]nonene
      and cis-disubstituted cyclopentane skeletons with a creation of three or two
      contiguous chiral centers in good yield with high diastereo- and excellent
      enantioselectivities.

PMID- 16287282
TI  - Screening mercury levels in fish with a selective fluorescent chemosensor.
AB  - Societal concerns over toxic mercury accumulation in humans from fish and other
      dietary and environmental sources provide motivation to develop new tools and
      tactics for mercury detection in a wide range of laboratory and field settings.
      Here we report the synthesis, properties, and application of a selective and
      sensitive small-molecule chemosensor for fluorescence screening of mercury levels
      in fish. Mercuryfluor-1 (MF1) is a water-soluble, fluorescein-based reagent that
      features excellent selectivity for Hg2+ over competing analytes and the largest
      turn-on fluorescence response to date (>170-fold increase) for reporting this
      heavy metal ion in aqueous solution. Combining this chemoselective Hg2+ probe
      with a microwave digestion protocol provides a facile method for assaying mercury
      levels in fish samples with mercury concentrations spanning 0.1 to 8 ppm, a range
      well matched with the United States Environmental Protection Agency (U.S. EPA)
      standard for the maximum safe level of mercury in edible fish (0.55 ppm).

PMID- 16287283
TI  - Structural snapshots of a flexible Cu2P2 core that accommodates the oxidation
      states Cu(I)Cu(I), Cu1.5Cu1.5, and Cu(II)Cu(II).
AB  - The phosphido-bridged dicopper(I) complex {(PPP)Cu}2 has been synthesized and
      structurally characterized ([PPP]- = bis(2-di-iso
      propylphosphinophenyl)phosphide). Cyclic voltammetry of {(PPP)Cu}2 in THF shows
      fully reversible oxidations at -1.02 V (Cu1.5Cu1.5/CuICuI) and -0.423 V
      (CuIICuII/Cu1.5Cu1.5). Chemical oxidation of {(PPP)Cu}2 by one electron yields
      the class III mixed-valence species [{(PPP)Cu}2]+ (EPR, UV-vis). Structural data
      establish an unexpectedly large change (0.538 A) in the Cu...Cu distance upon
      oxidation state. Oxidation of {(PPP)Cu}2 by two electrons yields the dication
      [{(PPP)Cu}2]2+, an antiferromagnetically coupled dicopper(II) complex.
      Maintenance of a pseudotetrahedral geometry that is midway between a square plane
      and an ideal tetrahedron at the copper centers, along with a high degree of
      flexibility at the phosphide hinges, allows for efficient access to CuICuI,
      Cu1.5Cu1.5, and CuIICuII redox states without the need for ligand exchange,
      substitution, or redistribution processes.

PMID- 16287284
TI  - Copper-catalyzed gamma-selective and stereospecific substitution reaction of
      allylic carbonates with diboron: efficient route to chiral allylboron compounds.
AB  - A copper-catalyzed gamma-selective and stereospecific substitution reaction of
      allylic carbonates with a diboron reagent affording allylboron compounds is
      described. Boryl group was selectively introduced at the gamma-position of the
      leaving carbonate group. Functionalized allylboronates that have an acetal,
      ester, or isolated alkene were prepared. The reaction of optically active allylic
      carbonates underwent complete alpha-to-gamma chirality transfer with anti
      stereochemistry to produce optically active allylboronates having a boron
      substituted stereogenic center.

PMID- 16287286
TI  - Total synthesis of lucilactaene, a cell cycle inhibitor active in p53-inactive
      cells.
AB  - Hetero-bis-metalated 1,3-butadiene is employed in the lynchpin coupling of
      synthetic fragments of the side chain of the antitumor agent, lucilactaene.
      Sequential Stille and Suzuki-Miyaura couplings interpolate this unique boron/tin
      diene into the pentaene chain. The total synthesis of lucilactaene was
      accomplished efficiently, in just eight linear steps.

PMID- 16287287
TI  - Synthesis of bifunctional polymer nanotubes from silicon nanowire templates via
      atom transfer radical polymerization.
AB  - As a way to control the surface properties of nanowires and nanotubes, we present
      a method for growing polymer from the surface of silicon/silica core/shell
      nanowires. After modification of nanowire surfaces with polymer initiators, Atom
      Transfer Radical Polymerization (ATRP) was used to grow methacrylate polymer
      chains from the surface. The resulting structures were characterized by SEM, TEM,
      and EELS. After etching the silicon cores, the resulting polymer-coated nanotubes
      will have hydrophilic silica cores with hydrophobic polymer shells.

PMID- 16287285
TI  - Steric constraint in the primary photoproduct of an archaeal rhodopsin from
      regiospecific perturbation of C-D stretching vibration of the retinyl
      chromophore.
AB  - In visual and archaeal rhodopsins, light energy is stored in the chromophore
      protein interaction after retinal photoisomerization. This paper reports a novel
      method to monitor the steric constraint after retinal isomerization by use of
      enhanced C-D stretching vibrations. In the difference FTIR spectra between an
      archaeal light-sensor pharaonis phoborhodopsin (ppR) and the primary K
      intermediate at 77 K, no peaks were observed in the 2160-2330 cm-1 region for
      deuterated retinals at position 7, 8, 10, 11, 12, and 15, whereas a strong peak
      appeared at 2244 cm-1 for the K intermediate of ppR possessing a C14-D-labeled
      retinal. The 2244-cm-1 band is assigned as the C14-D stretching vibration, and
      enhanced absorption in the K state probably originates from the local steric
      constraint at the C14-D position (also possible electrostatic field effects)
      after the C13=C14 double bond rotation.

PMID- 16287288
TI  - Hydroacylation of 2-vinyl benzaldehyde systems: an efficient method for the
      synthesis of chiral 3-substituted indanones.
AB  - Asymmetric rhodium-catalyzed hydroacylation has been utilized in the synthesis of
      3-substituted indanones with high conversions and enantioselectivity. The
      hydroacylation reaction of 2-vinyl benzaldehyde had been previously reported to
      give a low yield of indanone and an unidentified product. We have identified this
      compound as a dimer of the starting material. Substitution at the alpha-position
      of the 2-vinyl benzaldehyde substrates blocks the competitive dimerization
      reaction and allows the reaction to proceed with yields generally greater than
      90%. Utilization of BINAP as a chiral ligand results in good chemical yields and
      enantioselectivity greater than 95% in most cases.

PMID- 16287290
TI  - Copper-catalyzed hydrative amide synthesis with terminal alkyne, sulfonyl azide,
      and water.
AB  - It is shown for the first time that N-sulfonyl amides can be efficiently prepared
      by an unconventional approach of the hydrative reaction between terminal alkynes,
      sulfonyl azides, and water in the presence of copper catalyst and amine base
      under very mild conditions. The present route is quite general, and a wide range
      of alkynes and sulfonyl azides are readily coupled catalytically with water to
      furnish amides in high yields. A variety of labile functional groups are
      tolerated under the conditions, and the reaction is regioselective in that only
      terminal alkynes react while double or internal triple bonds are intact. The
      reaction can be readily scaled up and is also adaptable to a solid-phase
      procedure with high efficiency.

PMID- 16287289
TI  - Tetrahydropyran rings from a Mukaiyama-Michael cascade reaction.
AB  - A new annulation reaction leading to tetrahydropyrans has been discovered. The
      reaction of homoallylic enol ethers (e.g., 1) with alpha,beta-unsaturated ketones
      or esters begins with a Mukaiyama-Michael addition. The intermediate oxocarbenium
      ion undergoes a rapid 2-oxonia-Cope rearrangement, and the resulting zwitterion
      collapses to form a tetrahydropyran. The reaction is stereoselective with 3
      butene-2-one, but leads to diastereomeric mixtures with ethyl acrylate. More
      complex enones, such as cyclohexenone, also undergo the reaction to produce fused
      ring products. The optical activity of the substrates is relayed in the
      tetrahydropyran products.

PMID- 16287291
TI  - Reactions of Al(n)I(x)- with methyl iodide: the enhanced stability of Al7I and
      the chemical significance of active centers.
AB  - Al(n)I(x)- are reacted with methyl iodide, and the reaction mechanisms and
      products are discussed. The relevance of previous studies of the reactions
      between bare aluminum clusters and methyl iodide is addressed, and the chemical
      differences reported herein are explained. Particular attention is given to
      parallels with the known chemistry of alkyl halides on aluminum surfaces, where
      kinetically mediated etching reactions are prominent. The emergence of Al7I- as
      the dominant product in the present reactions is addressed via electronic
      structure calculations, which reveal that the cluster can be described in terms
      of an electron bound to a "jellium compound". Other significant products of the
      etching reaction include I-, I3-, and, importantly, the polyhalide-like Al13I2x-
      clusters. In the Al13I(x)- series, clusters with odd values for x are found to be
      reactive, and those with even x are far more stable. This observation is
      explained in terms of the presence or absence of active sites.

PMID- 16287292
TI  - Charge shift and triplet state formation in the 9-mesityl-10-methylacridinium
      cation.
AB  - The target donor-acceptor compound forms an acridinium-like, locally excited (LE)
      singlet state on illumination with blue or near-UV light. This LE state undergoes
      rapid charge transfer from the acridinium ion to the orthogonally sited mesityl
      group in polar solution. The resultant charge-transfer (CT) state fluoresces in
      modest yield and decays on the nanosecond time scale. The LE and CT states reside
      in thermal equilibrium at ambient temperature; decay of both states is weakly
      activated in fluid solution, but decay of the CT state is activationless in a
      glassy matrix. Analysis of the fluorescence spectrum allows precise location of
      the relevant energy levels. Intersystem crossing competes with radiative and
      nonradiative decay of the CT state such that an acridinium-like, locally excited
      triplet state is formed in both fluid solution and a glassy matrix.
      Phosphorescence spectra position the triplet energy well below that of the CT
      state. The triplet decays via first-order kinetics with a lifetime of ca. 30
      micros at room temperature in the absence of oxygen but survives for ca. 5 ms in
      an ethanol glass at 77 K. The quantum yield for formation of the LE triplet state
      is 0.38 but increases by a factor of 2.3-fold in the presence of iodomethane. The
      triplet reacts with molecular oxygen to produce singlet molecular oxygen in high
      quantum yield. In sharp contradiction to a recent literature report, there is no
      spectroscopic evidence to indicate the presence of an unusually long-lived CT
      state.

PMID- 16287293
TI  - Observation of the anisotropic photoinduced magnetization effect in Co-Fe
      Prussian blue thin films fabricated by using clay Langmuir-Blodgett films as a
      template.
AB  - Thin films of cobalt-iron cyanide (Co-Fe Prussian blue) have been fabricated by
      means of the modified Langmuir-Blodgett (LB) method using a smectite clay mineral
      (montmorillonite). In this combined method, clay LB films play a template role in
      the formation of the Co-Fe Prussian blue thin layer. The films were revealed to
      possess a well-organized structure not only in perpendicular directions to the
      film surface but also in parallel directions to the film surface. The
      photoinduced electron transfer from the iron ion to the cobalt through the
      bridging cyanide in the films occurred at low temperature (8 K), similar to that
      in the bulk Co-Fe Prussian blue. The films clearly exhibited magnetic anisotropy
      with regards to the direction of the applied magnetic field. Moreover, the
      photoinduced magnetization effect in the films was also found to be anisotropic.

PMID- 16287294
TI  - Sequence-dependent conformational energy of DNA derived from molecular dynamics
      simulations: toward understanding the indirect readout mechanism in protein-DNA
      recognition.
AB  - Sequence dependence of DNA conformation plays a crucial role in its recognition
      by proteins and ligands. To clarify the relationship between sequence and
      conformation, it is necessary to quantify the conformational energy and
      specificity of DNA. Here, we make a systematic analysis of dodecamer DNA
      structures including all the 136 unique tetranucleotide sequences at the center
      by molecular dynamics simulations. Using a simplified conformational model with
      six parameters to describe the geometry of adjacent base pairs and harmonic
      potentials along these coordinates, we estimated the equilibrium conformational
      parameters and the harmonic potentials of mean force for the central base-pair
      steps from many trajectories of the simulations. This enabled us to estimate the
      conformational energy and the specificity for any given DNA sequence and
      structure. We tested our method by using sequence-structure threading to estimate
      the conformational energy and the Z-score as a measure of specificity for many B
      DNA and A-DNA crystal structures. The average Z-scores were negative for both
      kinds of structures, indicating that the potential of mean force from the
      simulation is capable of predicting sequence specificity for the crystal
      structures and that it may be used to study the sequence specificity of both
      types of DNA. We also estimated the positional distribution of conformational
      energy and Z-score within DNA and showed that they are strongly position
      dependent. This analysis enabled us to identify particular conformations
      responsible for the specificity. The presented results will provide an insight
      into the mechanisms of DNA sequence recognition by proteins and ligands.

PMID- 16287295
TI  - Redox-transmetalation process as a generalized synthetic strategy for core-shell
      magnetic nanoparticles.
AB  - Although multicomponent core-shell type nanomaterials are one of the highly
      desired structural motifs due to their simultaneous multifunctionalities, the
      fabrication strategy for such nanostructures is still in a primitive stage. Here,
      we present a redox-transmetalation process that is effective as a general
      protocol for the fabrication of high quality and well-defined core-shell type
      bimetallic nanoparticles on the sub-10 nm scale. Various core-shell type
      nanomaterials including Co@Au, Co@Pd, Co@Pt, and Co@Cu nanoparticles are
      fabricated via transmetalation reactions. Compared to conventional sequential
      reduction strategies, this transmetalation process has several advantages for the
      fabrication of core-shell type nanoparticles: (i) no additional reducing agent is
      needed and (ii) spontaneous shell layer deposition occurs on top of the core
      nanoparticle surface and thus prevents self-nucleation of secondarily added
      metals. We also demonstrate the versatility of these core-shell structures by
      transferring Co@Au nanoparticles from an organic phase to an aqueous phase via a
      surface modification process. The nanostructures, magnetic properties, and
      reaction byproducts of these core-shell nanoparticles are spectroscopically
      characterized and identified, in part, to confirm the chemical process that
      promotes the core-shell structure formation.

PMID- 16287296
TI  - Spectroscopic and computational studies of the de novo designed protein DF2t:
      correlation to the biferrous active site of ribonucleotide reductase and factors
      that affect O2 reactivity.
AB  - DF2t, a de novo designed protein that mimics the active-site structure of many
      non-heme biferrous enzymes, has been studied using a combination of circular
      dichroism (CD), magnetic circular dichroism (MCD), and variable-temperature
      variable-field (VTVH) MCD. The active site of DF2t is found to have one five
      coordinate iron and one four-coordinate iron, which are weakly
      antiferromagnetically coupled through a mu-1,3 carboxylate bridge. These results
      bear a strong resemblance to the spectra of Escherichia coli ribonucleotide
      reductase (R2), and density functional theory calculations were conducted on the
      W48F/D84E R2 mutant in order to determine the energetics of formation of a
      monodentate end-on-bound O2 to one iron in the binuclear site. The mu-1,3
      carboxylate bridges found in O2-activating enzymes lack efficient superexchange
      pathways for the second electron transfer (i.e., the OH/oxo bridge in
      hemerythrin), and simulations of the binding of O2 in a monodentate end-on manner
      revealed that the bridging carboxylate ligands do not appear capable of
      transferring an electron to O2 from the remote Fe. Comparison of the results from
      previous studies of the mu-1,2 biferric-peroxo structure, which bridges both
      irons, finds that the end-on superoxide mixed-valent species is considerably
      higher in energy than the bridging peroxo-diferric species. Thus, one of the
      differences between O2-activating and O2-binding proteins appears to be the
      ability of O2 to bridge both Fe centers to generate a peroxo intermediate capable
      of further reactivity.

PMID- 16287297
TI  - Photoswitched cell adhesion on surfaces with RGD peptides.
AB  - Coating of surfaces by RGD peptides is well-known. Herein we describe the
      possibility to switch cell adhesion properties by changing the distance and
      orientation of the RGD peptides to the surface. A set of RGD peptides of the type
      cyclo(-RGDfK-) was synthesized containing the photoswitchable 4-[(4
      aminophenyl)azo]benzocarbonyl central unit as spacer between the acrylamide
      anchor and the RGD peptide. PMMA (poly methyl methacrylate) surfaces were coated
      with these peptides. Control of adhesion stimulation by irradiation with 366 or
      450 nm light could be achieved.

PMID- 16287298
TI  - Geometry, phase stability, and electronic properties of isolated selenium chains
      incorporated in a nanoporous matrix.
AB  - We report the fabrication process of isolated one-dimensional Se chains
      incorporated in the matrix of AlPO4-5 single crystals and the experimental
      investigation of the geometry, phase stability, electronic properties, and
      electron-phonon coupling effect of these Se chains. The structure of the helical
      Se chains inside the channels is discussed on the basis of X-ray scattering
      measurements. Thermal analysis and temperature-dependent micro-Raman measurements
      show that Se single chains are flexible and can convert from a weak distorted
      phase into another phase with strongly disordered structure ("melting" state)
      around 340 K. Since the electrons are confined in the one-dimensional channels,
      the absorption band of the Se chain is obviously blue shifted compared with that
      of trigonal Se. With increasing temperature, this band shifts linearly to the
      lower energy side, in sharp contrast to the nonlinear temperature coefficient of
      trigonal Se, which is attributed to the greatly diminished interchain interaction
      and the weakening of the electron-optical phonon coupling in a low-dimensional
      system. In the vicinity of the absorption band, both first-order and second-order
      Raman signals for the Se chain are enhanced, due to the strong electron-phonon
      coupling when the excitation laser energy matches the electronic transition in
      isolated Se chains.

PMID- 16287299
TI  - The dynamics of the B-A transition of natural DNA double helices.
AB  - The dynamics of the B-A transition of DNA double helices with different GC
      contents and various chain lengths has been characterized by an electric field
      pulse technique. The field-induced B-A reaction is separated from orientation
      effects using the magic angle technique. Amplitudes reflecting the B-A reaction
      are observed selectively in the limited range of ethanol contents, where CD
      spectra demonstrate the B-A transition. The maximum amplitude appears at 1-2%
      higher ethanol content than the center of the B-A transition observed by CD
      because electric field pulses induce a relatively large perturbation from the A-
      toward the B-form. The relaxation curves measured after pulse termination reflect
      a spectrum of up to three relaxation processes. For DNA's with approximately 50%
      GC, the main part of the amplitude ( approximately 75%) is associated with time
      constants of approximately 2 micros, and another major component appears with
      time constants of 50-100 micros. These relaxation effects have been observed for
      DNA samples with 859, 2629, 7160, and 48501 bp. The time constant associated with
      the main amplitude increases with decreasing GC content from approximately 2
      micros at 50% GC to approximately 3 mus at 41% GC and approximately 10 micros at
      0% GC at the center of the B-A transition. Model calculations on the kinetics of
      cooperative linear Ising lattices predict the appearance of a distinct maximum of
      the mean relaxation time at the center of the transition. The absence of such
      maximum in our experimental data indicates a low cooperativity of the B-A
      transition with a nucleation parameter of approximately 0.1. The rate of the B-A
      transition is lower by approximately 3 orders of magnitude than that predicted by
      molecular dynamics simulations.

PMID- 16287300
TI  - Evidence for a two-step mechanism in electronically selective single-walled
      carbon nanotube reactions.
AB  - Covalent and noncovalent chemistries that are selective to single-walled carbon
      nanotubes of a particular electronic type have become increasingly important for
      electronic structure separation and on-chip modification of nanoelectronic
      devices. By monitoring transient Raman spectroscopy and photoluminescence (PL)
      during a reaction with 4-chlorobenzene diazonium in aqueous solution, evidence
      for a characteristic two-step mechanism with two distinct time constants is
      uncovered. A long-lived intermediate selectively and noncovalently binds and
      partially dopes the nanotube surface (tau = 2.4 min). A slower, covalent reaction
      is tracked using the time-dependent increase in the disorder mode in Raman (tau =
      73 min). The transient Raman and PL data are well described using a series of two
      first-order reactions. The covalent bonding step can be deactivated by changing
      the structure of the surfactant adsorbed phase, further supporting the mechanism.

PMID- 16287301
TI  - Synthesis of two types of nanoparticles in polyelectrolyte capsule nanoreactors
      and their dual functionality.
AB  - Polyelectrolyte multilayer capsule reactors (PEMCRs) for the synthesis of two
      types of nanoparticles were prepared. The tunable PEMCRs containing two different
      functional groups that can be used to synthesize two types of nanoparticles
      simultaneously and to control the composition of two types of nanoparticles
      within the shell of PEMCs. These PEMCRs enabled the composition as well as the
      amount of the loaded two types of nanoparticles within the shell of PEMCs to be
      controlled by the copolymer ratio and the number of reaction cycles. Another
      interesting finding is that, as a result of the synthesis of two types of
      nanoparticles, these specially designed PEMCs containing both silver and goethite
      nanocrystals can be used as antimicrobial capsules, which can move by an external
      magnetic field. Such a technology has the potential for use in sterilization at
      the desirable sites.

PMID- 16287302
TI  - [12]Annulynes.
AB  - Only one isomer of o-benzyne ([6]annulyne or 1,2-didehydrobenzene) exists, but
      the dehydro analogue of the "ring-opened double benzene", [12]annulyne, was
      generated in several isomeric forms. 1,5-Hexadiyne undergoes self-condensation in
      the presence of potassium tert-butoxide to yield two isomers of [12]annulyne
      (3,11-di-trans-[12]annulyne and 5,9-di-trans-[12]annulyne), both of which exhibit
      a weak paratropic ring current in their 1H NMR spectra and are oxygen sensitive.
      They can be reduced to their respective dianions, which are diatropic. A third
      isomer (3,9-di-trans-[12]annulyne) was generated via the complete
      dehydrohalogenation of hexabromocyclododecene and found to be much less stable
      but can be tamed via one- or two-electron reduction. A tight association of the
      cation (K+) with the p(y)-orbitals within the alkyne moiety results in an
      unusually low-field resonance for an adjacent external proton.

PMID- 16287303
TI  - Geometry and cooperativity effects in adenosine-carboxylic acid complexes.
AB  - NMR experiments and theoretical investigations were performed on hydrogen bonded
      complexes of specifically 1- and 7-15N-labeled adenine nucleosides with
      carboxylic acids. By employing a freonic solvent of CDClF2 and CDF3, NMR spectra
      were acquired at temperatures as low as 123 K, where the regime of slow hydrogen
      bond exchange is reached and several higher-order complexes were found to coexist
      in solution. Unlike acetic acid, chloroacetic acid forms Watson-Crick complexes
      with the proton largely displaced from oxygen to the nitrogen acceptor in an ion
      pairing structure. Calculated geometries and chemical shifts of the proton in the
      hydrogen bridge favorably agree with experimentally determined values if
      vibrational averaging and solvent effects are taken into account. The results
      indicate that binding a second acidic ligand at the adenine Hoogsteen site in a
      ternary complex weakens the hydrogen bond to the Watson-Crick bound carboxylic
      acid. However, substituting a second adenine nucleobase for a carboxylic acid in
      the trimolecular complex leads to cooperative binding at Watson-Crick and
      Hoogsteen faces of adenosine.

PMID- 16287304
TI  - Oxidative activation of n-butane on sulfated zirconia.
AB  - Catalytic activation and conversion of light alkanes by sulfated zirconia is
      unequivocally shown to be initiated by producing small concentrations of olefins.
      This occurs via stoichiometric oxidative dehydrogenation of butane by SO3 or
      pyrosulfate groups to butene (present mostly as alkoxy groups), water, and SO2.
      Thermal desorption and in situ IR spectroscopy have been used to determine all
      three reaction products. The concentration of butene formed determines both the
      catalytic activity of sulfated zirconia as well as the deactivation via formation
      of oligomers. The thermodynamics of the oxidative dehydrogenation of n-butane by
      different SZ surface structures has been examined by density functional (DFT)
      calculations. The calculations show that pyrosulfate or re-adsorbed SO3 species
      have the highest oxidizing ability.

PMID- 16287305
TI  - Enthalpy-entropy compensation is not a general feature of weak association.
AB  - Relationships between the enthalpy and entropy changes resulting from
      perturbations of a system have been discussed in the literature for some time.
      Both positive correlations (compensation) and negative correlations (anti
      compensation) between deltaH and DeltaS have been observed in various
      experimental contexts, including chemical reaction, physical association,
      solvation, and protein folding. Many examples have been demonstrated to be
      statistical artifacts, but some are genuine signatures of the perturbations in
      molecular characteristics. In particular, recent literature claims that
      compensation is a general feature of bimolecular associations arising from weak
      intermolecular interactions. We employ a statistical mechanical framework to
      predict the magnitude and direction of enthalpy-entropy correlation in
      bimolecular association. The theory links the macroscale thermodynamic
      correlation to the relationship between the intermolecular potential parameters.
      Using a harmonic approximation to the Lennard-Jones model and potential
      parameters taken from the literature, we show examples of both compensation and
      anti-compensation for gas-phase self-association among five homologous series.
      Furthermore, an aggregate presentation of data for 48 different chemical species
      shows no correlation in either direction, for the case of self-association in a
      dilute gas phase.

PMID- 16287306
TI  - Evidences for zeolite nucleation at the solid-liquid interface of gel cavities.
AB  - The entire sequence of crystallization events, starting with formation of the
      initial organic-cation-free gel, proceeding through the zeolite nucleation stage,
      and finishing with complete transformation into LTA-type zeolite crystals, has
      been monitored by means of high-resolution transmission electron microscopy.
      Formation and development of voids, containing highly hydrated material
      transformed later into negative crystals, has been discovered in the solid part
      of the system. The evolution of these areas has been found to be an integral and
      noteworthy part of the chemical transformation of the gel that preceded the
      nucleation in the system. These void structures and, in particular, their solid
      liquid interfaces have been identified as the specific locations where the
      formation of protozeolite nuclei took place. Further development of the system
      followed the classical for zeolite-yielding systems of crystallization that could
      be described by the autocatalytic model.

PMID- 16287307
TI  - A new class of macrocyclic lanthanide complexes for cell labeling and magnetic
      resonance imaging applications.
AB  - Lanthanide complexes have wide applications in biochemical research and
      biomedical imaging. We have designed and synthesized a new class of macrocyclic
      lanthanide chelates, Ln/DTPA-PDA-C(n), for cell labeling and magnetic resonance
      imaging (MRI) applications. Two lipophilic Gd3+ complexes, Gd/DTPA-PDA-C(n) (n =
      10, 12), labeled a number of cultured mammalian cells noninvasively at
      concentrations as low as a few micromolar. Cells took up these agents rapidly and
      showed robust intensity increases in T1-weighed MR images. Labeled cells showed
      normal morphology and doubling time as control cells. In addition to cultured
      cells, these agents also labeled primary cells in tissues such as dissected
      pancreatic islets. To study the mechanism of cellular uptake, we applied the
      technique of diffusion enhanced fluorescence resonance energy transfer (DEFRET)
      to determine the cellular localization of these lipophilic lanthanide complexes.
      After loading cells with a luminescent complex, Tb/DTPA-PDA-C10, we observed
      DEFRET between the Tb3+ complex and extracellular, but not intracellular,
      calcein. We concluded that these cyclic lanthanide complexes label cells by
      inserting two hydrophobic alkyl chains into cell membranes with the hydrophilic
      metal binding site facing the extracellular medium. As the first imaging
      application of these macrocyclic lanthanide chelates, we labeled insulin
      secreting beta-cells with Gd/DTPA-PDA-C12. Labeled cells were encapsulated in
      hollow fibers and were implanted in a nude mouse. MR imaging of implanted beta
      cells showed that these cells could be followed in vivo for up to two weeks. The
      combined advantages of this new class of macrocyclic contrast agents ensure
      future imaging applications to track cell movement and localization in different
      biological systems.

PMID- 16287309
TI  - Energetics of binuclear spin transition complexes.
AB  - The electronic structures of five binuclear iron(II) complexes, four of which
      display spin transitions between the low-spin (LS) and high-spin (HS) electronic
      states, are studied by density functional theory (DFT) calculations. Three
      electronic states, corresponding to [LS-LS], [LS-HS], and [HS-HS] electronic
      configurations, are characterized. The nature of the ground state agrees with the
      experimentally observed magnetic state of complexes stabilized at low
      temperatures. The results of the calculations agree with the conclusion of the
      phenomenological model, that the enthalpy of the [LS-HS] state must be lower than
      the average enthalpy of the [LS-LS] and [HS-HS] states, to create conditions for
      a two-step spin transition. The exchange parameters between Fe(II) ions in the
      [HS-HS] states are evaluated. It is shown that all complexes are weakly
      antiferromagnetic and the synergy between two spin transition centers is mainly
      of elastic origin.

PMID- 16287310
TI  - Matrix-induced intensity fluctuations in the fluorescence from single
      oligo(phenylenevinylene) molecules.
AB  - Single molecule spectroscopy on oligo(phenylenevinylene) (OPV) chromophores shows
      that the fluorescence intermittency strongly correlates to the rigidity of the
      environment surrounding the molecules. For OPV single molecules, environmental
      rigidity inhibits twisting about the vinyl linkages, the molecular motion
      associated with the observed "off" (nonabsorbing) state. By increasing the
      rigidity of a single molecule's environment, we can tune its room temperature
      fluorescence from rapid, sub-millisecond "blinking" fluctuations (fluid polymer
      environment) to completely "on" with no blinking observed (molecules adsorbed to
      a rigid bare glass substrate). The difference in fluorescence intermittency from
      environment to environment is immediately apparent and explicit in single
      molecule intensity trajectories under cw (continuous wave) excitation,
      demonstrating the sensitivity of these chromophores to their surroundings and
      emphasizing the importance of morphological control in real-world applications
      involving phenylenevinylene-based materials.

PMID- 16287308
TI  - Regulation of saccharide binding with basic poly(ethynylpyridine)s by H+-induced
      helix formation.
AB  - A basic host polymer exhibiting pH-regulatable saccharide recognition has been
      investigated. Poly(m-ethynylpyridine) bearing dialkylamino groups forms helical
      complexes with saccharides to show induced circular dichroism (ICD). When
      trifluoroacetic acid was titrated on these complexes, the ICD was gradually
      enhanced until the amount of the acid reached ca. 0.5 molar equivalence versus
      the pyridine rings in the polymer, and further addition of the acid suppressed
      the ICD. The proper addition of the acid also increased the binding constants
      between the polymer and saccharides. These findings would be due to stabilization
      of the helical structure consisting of cisoid conformations for each of the
      adjacent pyridine pairs, which were caused by half-protonation of the pyridine
      rings. Computational analyses indicated that the pyridinium-pyridine dimeric
      structure prefers its cisoid conformation to its transoid one.

PMID- 16287311
TI  - A DFT study of the thermal, orbital symmetry forbidden, cyclophanediene to
      dihydropyrene electrocyclic reaction. Predictions to improve the
      dimethyldihydropyrene photoswitches.
AB  - The orbital symmetry forbidden thermal electrocyclic equilibria between a series
      of cyclophanedienes and dimethyldihydropyrenes (CPD<==>DDPs) were studied using
      density functional theory (DFT). These reactions are important not only because
      of their fundamental interest but also in how they restrict the potential utility
      of the DDP photoswitches by limiting the thermal lifetime of the CPDs. The
      transition states (TSs) for these reactions could not be modeled using restricted
      DFT (RB3LYP) but were located using unrestricted DFT (UB3LYP). Each TS possesses
      significant biradical character as indicated by their spin contaminated wave
      functions, S2 not = 0. Specific substitution by nitrile or trifluoromethyl
      group(s) is predicted to strongly affect the magnitude of the activation barriers
      for these reactions. In particular, replacing the internal methyl groups of the
      CPDs/DDPs with nitrile groups is predicted to have the maximum effect and to
      raise the activation barriers and lifetimes of the CPDs considerably.

PMID- 16287312
TI  - Thermodynamics and kinetics of PNA-DNA quadruplex-forming chimeras.
AB  - PNA-DNA chimeras present the interesting properties of PNA, such as the high
      binding affinity to complementary single-strand (DNA or RNA), and the resistance
      to nuclease and protease degradation. At the same time, the limitations of an
      oligomer containing all PNA residues, such as low water solubility, self
      aggregation, and low cellular uptake, are effectively overcome. Further, PNA-DNA
      chimeras possess interesting biological properties as antisense agents. We have
      explored the ability of PNA-DNA chimeric strands to assemble in quadruplex
      structures. The rate constant for association of the quadruplexes and their
      thermodynamic properties have been determined by CD spectroscopy and differential
      scanning calorimetry (DSC). Thermal denaturation experiments indicated higher
      thermal and thermodynamic stabilities for chimeric quadruplexes in comparison
      with the corresponding unmodified DNA quadruplex. Singular value decomposition
      analysis (SVD) suggests the presence of kinetically stable intermediate species
      in the quadruplex formation process. The experimental results have been discussed
      on the basis of molecular dynamic simulations. The ability of PNA-DNA chimeras to
      form stable quadruplex structures expands their potential utility as therapeutic
      agents.

PMID- 16287313
TI  - Heme release in myoglobin-DDAB films and its role in electrochemical NO
      reduction.
AB  - Electrochemical nitric oxide (NO) reduction by heme groups incorporated in films
      of didodecyldimethylammonium bromide (DDAB) on pyrolitic graphite was
      investigated. It is shown that DDAB most likely induces the release of the heme
      group from myoglobin and therefore myoglobin-DDAB and heme-DDAB films give the
      same voltammetric responses. This is confirmed by UV/vis spectroscopy showing a
      clear shift in the Soret band of myoglobin in a DDAB solution. The
      electrochemical NO reduction on a heme-DDAB film at different pH values reveals
      the presence of pH-dependent and pH-independent NO reduction pathways. The
      selectivity of these pathways is probed by combining the rotating ring-disk
      electrode technique with online electrochemical mass spectroscopy showing that
      the product of the pH-independent pathway is N2O and the product of the pH
      dependent pathway is NH2OH. The preference for one or the other pathway seems to
      depend on whether a proton or a NO molecule is transferred to a Fe(II)-NO-
      reaction intermediate and is influenced by pH, NO concentration, and potential.

PMID- 16287314
TI  - High anisotropy of the field-effect transistor mobility in magnetically aligned
      discotic liquid-crystalline semiconductors.
AB  - A magnetic field has been utilized for producing highly oriented films of a
      substituted hexabenzocoronene (HBC). Optical microscopy studies revealed large
      area HBC monodomains that covered the entire film, while wide-angle X-ray
      measurements showed that the HBC molecules are aligned with their planes along
      the applied field. On the basis of this method, solution-processed field-effect
      transistors (FET) have been constructed with charge carrier mobilities of up to
      10(-3) cm2/V.s, which are significantly enhanced with respect to the unaligned
      material. Exceptionally high mobility anisotropies of 25-75 for current flow
      parallel and perpendicular to the alignment direction have been measured as a
      function of the channel length. Atomic force microscopy performed on the FET
      structures reveals fibril superstructures that are oriented perpendicularly to
      the magnetic field direction, consisting of molecular columns with a slippage
      angle of 40 degrees between the molecules. For channel lengths larger than 2.5
      mum, the fibrils are smaller than the electrode spacing, which adversely affects
      the device performance.

PMID- 16287315
TI  - Improved molecular rectification from self-assembled monolayers of a sterically
      hindered dye.
AB  - Self-assembled monolayers (SAMs) formed from the reaction of 1-(10
      acetylsulfanyldecyl)-4-[2-(4-dimethylaminonaphthalen-1-yl)-vinyl]-quinolinium
      iodide (1a) and gold-coated substrates exhibit asymmetric current-voltage (I-V)
      characteristics with a rectification ratio of 50-150 at +/-1 V. It is the highest
      to date for a molecular diode, and the improved behavior may be assigned in part
      to the controlled alignment of the donor-(pi-bridge)-acceptor moieties and in
      part to steric hindrance, which imposes a nonplanar structure and effectively
      isolates the molecular orbitals of the donor and acceptor end groups. The
      molecular origin of the rectification is verified by its suppression upon
      exposure to HCl vapor, which protonates the dimethylamino group and inhibits the
      electron-donating properties, with restoration upon exposure to NH3. It is also
      established by a reduced rectification ratio of ca. 2 at +/-1 V when the cationic
      D-pi-A+ moieties adopt an antiparallel arrangement in self-assembled films of the
      derivative, bis-[1-(10-decyl)-4-[2-(4-dimethylaminonaphthalen-1-yl)-vinyl]
      quinolinium]-disulfide diiodide (1b), which adsorbs via one of its terminal
      donors without rupture of the sulfur-sulfur bond: Au/D-pi-A+-C10H20-S-S-C10H20-+A
      pi-D (I-)2.

PMID- 16287316
TI  - Structural evolution of hexa-peri-hexabenzocoronene adlayers in heteroepitaxy on
      n-pentacontane template monolayers.
AB  - The growth and structure of self-assembled adlayers of hexakis(n-dodecyl)-peri
      hexabenzocoronene (HBC-C12) adsorbed on highly ordered pyrolitic graphite (HOPG)
      decorated by an n-pentacontane (n-C50H102) monolayer have been investigated by
      scanning tunneling microscopy (STM). Whereas on HOPG the HBC-C12 molecules
      readily self-assemble into a unique stable 2D structure, on the [n-C50H102
      monolayer/graphite] system we observe morphological phase transitions with
      formation of time dependent alpha, beta, and gamma phases (alpha-->beta-->gamma).
      The initial alpha-phase is similar to that obtained on bare graphite, while
      intermediate beta- and final gamma-structures present molecular dimers and rows,
      respectively. The observed two-dimensional polymorphism is due to weak
      interaction between HBC-C12 molecules and n-C50H102-modified graphite substrate.
      Our results constitute an important step toward the control of the growth and
      structure of highly ordered monolayers of functional conjugated molecules by
      modifying the graphite surface with an n-alkane monolayer of appropriate chain
      length.

PMID- 16287317
TI  - Measuring antiaromaticity by an analysis of ring current and coupling constant
      changes in a cyclopentadienone-fused dihydropyrene.
AB  - The synthesis of the chloro- and parent cyclopentadienone-fused dihydropyrenes 10
      and 7 are reported. Analysis of coupling constants, and chemical shift changes
      between these and the nonconjugated dihydro derivatives 11 and 8, and between the
      benzannulene 4 and the parent annulene 12, indicates without doubt that
      cyclopentadienone is behaving as an antiaromatic 4n-pi system and that in its
      effect on the ring current of 12, cyclopentanedienone has about 80% of the effect
      of benzene. This is the first time that a suitable probe has been used to
      estimate the relative ability of a 4n-pi system to bond localize the probe in
      comparison to the (4n + 2)-pi system benzene.

PMID- 16287318
TI  - Regiospecific and stereoselective syntheses of (+/-)-reserpine and (-)-reserpine.
AB  - Full details of three approaches to an entirely regio- and stereoselective
      synthesis of the well-known target reserpine are described, culminating in a
      total synthesis which efficiently meets these requirements.

PMID- 16287320
TI  - Very large swelling in hybrid frameworks: a combined computational and powder
      diffraction study.
AB  - Using a combination of simulations and powder diffraction, we report here the
      study of the very large swelling of a three-dimensional nanoporous iron(III)
      carboxylate (MIL-88) which exhibits almost a reversible doubling (approximately
      85%) of its cell volume while fully retaining its open-framework topology. The
      crystal structure of the open form of MIL-88 has been successfully refined and
      indicates that atomic displacements larger than 4 angstroms are observed when
      water or various alcohols are adsorbed in the porous structure, revealing an
      unusually flexible crystallized framework. X-ray thermodiffractometry shows that
      only a displacive transition occurs during the swelling phenomenon, ruling out
      any bond breaking.

PMID- 16287319
TI  - Shock-absorbing and failure mechanisms of WS2 and MoS2 nanoparticles with
      fullerene-like structures under shock wave pressure.
AB  - The excellent shock-absorbing performance of WS2 and MoS2 nanoparticles with
      inorganic fullerene-like structures (IFs) under very high shock wave pressures of
      25 GPa is described. The combined techniques of X-ray diffraction, Raman
      spectroscopy, X-ray photoelectron spectroscopy, thermal analysis, and
      transmission electron microscopy have been used to evaluate the diverse,
      intriguing features of shock recovered IFs, of interest for their tribological
      applications, thereby allowing improved understanding of their antishock behavior
      and structure-property relationships. Two possible failure mechanisms are
      proposed and discussed. The supershock-absorbing ability of the IF-WS2 enables
      them to survive pressures up to 25 GPa accompanied with concurrent temperatures
      of up to 1000 degrees C without any significant structural degradation or phase
      change making them probably the strongest cage molecules now known.

PMID- 16287321
TI  - Self-organization of a self-assembled supramolecular rectangle, square, and three
      dimensional cage on Au111 surfaces.
AB  - The structure and conformation of three self-assembled supramolecular species, a
      rectangle, a square, and a three-dimensional cage, on Au111 surfaces were
      investigated by scanning tunneling microscopy. These supramolecular assemblies
      adsorb on Au111 surfaces and self-organize to form highly ordered adlayers with
      distinct conformations that are consistent with their chemical structures. The
      faces of the supramolecular rectangle and square lie flat on the surface,
      preserving their rectangle and square conformations, respectively. The three
      dimensional cage also forms well-ordered adlayers on the gold surface, forming
      regular molecular rows of assemblies. When the rectangle and cage were mixed
      together, the assemblies separated into individual domains, and no mixed adlayers
      were observed. These results provide direct evidence of the noncrystalline solid
      state structures of these assemblies and information about how they self-organize
      on Au111 surfaces, which is of importance in the potential manufacturing of
      functional nanostructures and devices.

PMID- 16287322
TI  - Electro pen nanolithography.
AB  - We introduce Electro Pen Nanolithography (EPN), a nanoscale chemical patterning
      technique. In a single sweep of an ink-coated, biased conducting Atomic Force
      Microscope (AFM) probe-tip, an underlying thin organic film is oxidized, and the
      ink molecules are transferred directly to the oxidized regions. Results using
      trialkoxysilane inks with functional terminal groups are presented, where the
      same ink-covered tips are used to image the pattern with zero bias. This
      technique provides very fast--exceeding 10 microm/s--writing speeds with line
      widths as small as 50 nm. Controlled multi-write operations permit the growth of
      an integer number of molecular layers. Multiple chemical patterns using a single
      probe-tip are demonstrated.

PMID- 16287323
TI  - Purification of endohedral trimetallic nitride fullerenes in a single, facile
      step.
AB  - A major hurdle hampering the development of fullerenes, endohedral
      metallofullerenes, and nanotubes has been the difficulty of obtaining high purity
      samples. Soots prepared in the usual manner via a Kratschmer-Huffman electric-arc
      generator consist of mixtures of insoluble carbonaceous materials and soluble
      fullerenes: C60, C70, C76, C78, C84, etc. When metals are introduced as
      endohedral species the complexity of the resultant soot is even greater because
      of the presence of multiple isomers of both the empty fullerenes and the
      endohedral metallofullerenes. Here, for the first time, we report that lanthanide
      trimetallic nitride endohedral metallofullerenes, A3N@C80 (A = lanthanide atom,
      e.g., Er, Gd, Ho, Lu, Sc, Tb, Tm, Y), can be obtained in pure form directly from
      as-prepared soots in a single facile step by taking advantage of their
      extraordinary kinetic chemical stability with respect to the other fullerenes in
      Diels-Alder reactions with a cyclopentadiene-functionalized resin. We show that
      careful control of conditions (stoichiometry, time, temperature) allows
      separation of fullerenes with different cage sizes, as well as isomeric species.
      Furthermore, the Diels-Alder reaction is thermally reversible, and we
      demonstrated that the bound empty-cage fullerenes and classical endohedral
      metallofullerenes can be recovered by displacement with maleic anhydride.

PMID- 16287324
TI  - An anion-dependent switch in selectivity results from a change of C-H activation
      mechanism in the reaction of an imidazolium salt with IrH5(PPh3)2.
AB  - Changing the counteranion along the series Br, BF4, PF6, SbF6 in their ion-paired
      2-pyridylmethyl imidazolium salts causes the kinetic reaction products with
      IrH5(PPh3)2 to switch from chelating N-heterocyclic carbenes (NHCs) having normal
      C2 (N path) to abnormal C5 binding (AN path). Computational work (DFT) suggests
      that the AN path involves C-H oxidative addition to Ir(III) to give Ir(V) with
      little anion dependence. The N path, in contrast, goes by heterolytic C-H
      activation with proton transfer to the adjacent hydride. The proton that is
      transferred is accompanied by the counteranion in an anion-coupled proton
      transfer, leading to an anion dependence of the N path, and therefore of the N/AN
      selectivity. The N path goes via Ir(III), not Ir(V), because the normal NHC is a
      much less strong donor ligand than the abnormal NHC. PGSE NMR experiments support
      the formation of ion-pair in both the reactants and the products. 19F,1H-HOESY
      NMR experiments indicate an ion-pair structure for the products that is
      consistent with the computational prediction (ONIOM(B3PW91/UFF)).

PMID- 16287325
TI  - Magnetic properties and crystal structure of a one-dimensional phase of
      tetrakis(mu2-benzoato-O,O')-bis(dimethyl sulfoxide)dicopper(II).
AB  - A new crystalline polymorphic phase of tetrakis(mu2-benzoato-O,O')-bis(dimethyl
      sulfoxide)dicopper(II) was obtained by direct synthesis, in space group P2(1)/n.
      The copper coordination is in a slightly distorted square pyramidal geometry with
      an intramolecular Cu...Cu distance of 2.6494(8) angstroms. The Cu-O distances of
      the two copper in a dimer are different, giving different chemical environments
      for each Cu ion. The crystal structure is built up of well-separated stacking
      columns oriented along the b-axis, with units uniformly spaced, producing a one
      dimensional (1-D) zigzag chain through Cu(II)-S...S-Cu(II) interdimer
      interactions [S...S separation: 3.975(2) angstroms]. Magnetization measurements
      in the range 2-300 K indicate two magnetic orderings, at low temperature (T < 10
      K) a weak ferromagnetic ordering is observed, and above this temperature an
      antiferromagnetic behavior takes place. ESR spectra at 300 and 77 K of a
      polycrystalline sample show the characteristic signal of zero-field with D =
      0.354 cm(-1), consistent with a ferromagnetic Cu...Cu exchange interaction at low
      temperature.

PMID- 16287326
TI  - Molecular recognition in structured matrixes: control of guest localization in
      block copolymer films.
AB  - We demonstrate the use of molecular recognition to control the spatial
      distribution of guest molecules within block copolymer films. Block copolymers
      bearing recognition units were combined with complementary and noncomplementary
      molecules, and the extent of segregation of these molecules into the different
      domain types within microphase-separated thin films was quantitatively analyzed
      using dynamic secondary ion mass spectrometry (SIMS). Complementarity between the
      guest molecules and the polymer functionalities proved to be a key factor and an
      efficient tool for directing the segregation preference of the molecules to the
      different domain types. The effect of segregation preference on the glass
      transition temperature was studied using differential scanning calorimetry (DSC),
      and the results corroborate the SIMS findings. In a complementary study, guests
      with tunable sizes (via dendron substituents) were used to control block
      copolymer morphology. Morphological characterization using transmission electron
      microscopy (TEM) and X-ray diffraction reveal that selectivity differences can be
      directly translated into the ability to obtain different morphologies from
      recognition unit-functionalized block copolymer scaffolds.

PMID- 16287328
TI  - Tandem catalysis: generating multiple contiguous carbon-carbon bonds through a
      ruthenium-catalyzed ring-closing metathesis/Kharasch addition.
AB  - Tandem catalysis can offer unique and powerful strategies for converting simple
      starting materials into more complex products in a single reaction vessel while
      generating less waste and minimizing handling. In this regard, Grubbs' ruthenium
      alkylidene (Cy3P)2Cl2Ru=CHPh is shown to catalyze two mechanistically distinct
      transformations to offer a unique protocol that effects multiple bond changes in
      a single operation. A tandem ruthenium-catalyzed olefin ring-closing metathesis
      (RCM)/Kharasch addition allows for the facile preparation of bicyclic [3.3.0],
      [4.3.0], and [5.3.0] ring systems in one step from the appropriately
      functionalized acyclic precursors. For substrates where the intramolecular
      Kharasch addition fails, an intermolecular Kharasch addition is possible. By
      combining the intra- and intermolecular Kharasch additions with RCM, three new
      contiguous carbon-carbon bonds with multiple stereocenters can be generated by
      the ruthenium catalyst in a controlled fashion in one operation through two
      mechanistically distinct pathways.

PMID- 16287327
TI  - Anionogenic ferromagnets.
AB  - Magnetism in molecules and solids is understood to originate from atoms in that
      part of the periodic table where a particular value of the angular momentum
      appears first (i.e., the 2p, 3d, and 4f series). In contrast to the many magnetic
      compounds containing transition metal or lanthanide atoms, ferromagnetism based
      on atoms from the 2p series is very rare. We report density functional
      calculations that show the existing compound rubidium sesquioxide is a
      ferromagnet with an estimated Curie temperature of 300 K, unprecedented in p
      electron magnetism. The magnetic moment is carried by the anion. Rubidium
      sesquioxide is a conductor, but only for the minority spin electrons (a so-called
      "half-metal"). Half-metals play an important role in spintronics, that is,
      electronics that exploits the electron spin. Since the magnetic moment resides on
      a light element (oxygen), spin-orbit interactions are considerably reduced
      compared to other half-metals. Consequently spin relaxation is expected to be
      suppressed by up to 2 orders of magnitude in comparison with materials presently
      used in spintronics.

PMID- 16287329
TI  - Controlled self-assembly of carbohydrate conjugate rod-coil amphiphiles for
      supramolecular multivalent ligands.
AB  - Carbohydrate conjugate rod-coil amphiphiles were synthesized and their self
      assembling behavior in aqueous solution was investigated. These amphiphiles were
      observed to self-assemble into supramolecular structures that differ
      significantly depending on the molecular architecture. The rod-coil amphiphiles
      based on a short coil (1) self-assemble into a vesicular structure, while the
      amphiphiles with a long coil (2) show a spherical micellar structure. In
      contrast, 3, based on a twin-rod segment, was observed to aggregate into
      cylindrical micelles with twice the diameter of molecular length scale. As a
      means to determine the binding activity to protein receptors of these
      supramolecular objects, hemagglutination inhibition assay was performed. The
      experiments showed that the supramolecular architecture has a significant effect
      on the binding activity. In addition, incubation experiments with Escherichia
      coli showed that mannose-coated objects specifically bind to the bacterial pili
      of the ORN 178 strain. These results demonstrate that precise control of the nano
      objects in shape and size by molecular design can provide control of the
      biological activities of the supramolecular materials.

PMID- 16287335
TI  - Screening for dementia. My father's favorite axiom is alive and well.

PMID- 16287336
TI  - Pruritic eruption of left axilla. Patient reports flare-ups during heat of
      summer.

PMID- 16287337
TI  - Compiling a complete medical history: challenges and strategies for taking a
      comprehensive history in the elderly.

PMID- 16287338
TI  - Should we screen for Alzheimer's disease? A review of the evidence for and
      against screening Alzheimer's disease in primary care practice.
AB  - Fewer than one-half of all Alzheimer's disease (AD) patients are currently
      diagnosed; approximately 25% are treated with antidementia compounds. Screening
      has been proposed to help combat underdiagnosis of AD. An emerging consensus
      suggest that the three keys to the successful treatment of Alzheimer's disease
      are early detection, use of currently approved medications to provide symptomatic
      treatment, and development of medications to slow and eventually halt disease
      progression. If early detection of Alzheimer's disease is the first step,
      screening would seem to be an important strategy. We review the arguments for and
      against screening and suggest several strategies and instruments that may be
      helpful in the context of screening for Alzheimer's disease in primary care
      practice.

PMID- 16287339
TI  - Herb-drug interactions. Interactions between saw palmetto and prescription
      medications.
AB  - Patients over age 50 typically present with one chronic disease per decade. Each
      chronic disease typically requires long-term drug therapy, meaning most older
      patients require several drugs to maintain health. Simultaneously, use of
      complementary and alternative medicine (CAM) has increased in the United States
      in the last 20 years, reaching 36% in 2002; herbal medicine use accounts for
      approximately 22% of all CAM use. Older adults often add herbal medicines to
      prescription medications, yet do not always inform their physicians. The drug
      metabolizing enzyme systems process all compounds foreign to the body, including
      prescription and herbal medications. Therefore use of both medicinals
      simultaneously has a potential for adverse interactions. This review, which
      discusses saw palmetto, is the last in a series covering the documented
      interactions among the top 5 efficacious herbal medicines and prescription drugs.

PMID- 16287340
TI  - Lactic acidosis. Lactic acidosis associated with metformin use in treatment of
      type 2 diabetes mellitus.
AB  - Metformin, an antihyperglycemic, is widely used in the treatment of type 2
      diabetes mellitus (DM). A rare, but important complication associated with this
      drug is the development of lactic acidosis: Overall mortality of lactic acidosis
      is approximately 50%. Certain subsets of patients taking metformin are at greater
      risk of developing lactic acidosis. This report discusses the development of
      metformin-associated lactic acidosis in four older adults admitted to an
      institution during a 2-month period, treatments, and outcomes. We recommend an
      aggressive treatment strategy of hemodialysis followed by peritoneal dialysis,
      continuous bicarbonate infusion, and tight glucose control. We review the
      cautions and contraindications of metformin use for the treatment of type 2 DM
      and report an educational plan for residents and staff instituted to improve drug
      complication awareness and reduce mortality.

PMID- 16287341
TI  - Choosing an antiepileptic. Selecting drugs for older patients with epilepsy.
AB  - After age 65, the incidence of epilepsy increases rapidly. Approximately 1.5% of
      Medicare recipients and 10% of nursing home residents are being treated with
      antiepileptic drugs (AEDs). The most commonly used AED is phenytoin, a first
      generation agent. Appropriate drug selection in this population is complicated by
      the fact that multiple comorbidity is commonplace. Most older patients receive a
      number of drugs in addition to AEDs. The average nursing home patient receives
      six additional medications. Age-related issues affecting the choice of an AED
      include changes in protein binding, decreases in hepatic and renal clearance, and
      alterations in gastrointestinal absorption. AEDs that do not have drug-drug
      interactions, are not metabolized by the liver, and are readily absorbed may be
      better suited for the elderly. This paper reviews the present knowledge base and
      attempts to develop a more rational approach to AED selection for the elderly.

PMID- 16287342
TI  - Maternal-fetal microtransfusions and HIV-1 mother-to-child transmission in
      Malawi.
AB  - BACKGROUND: Between 25% and 35% of infants born to HIV-infected mothers become
      HIV-1 infected. One potential route of mother-to-child transmission (MTCT) could
      be through a breakdown in the placental barrier (i.e., maternal-fetal
      microtransfusions). METHODS AND FINDINGS: Placental alkaline phosphatase (PLAP)
      is a 130-kD maternal enzyme that cannot cross the intact placental barrier. We
      measured PLAP activity in umbilical vein serum as an indicator of maternal-fetal
      microtransfusion, and related this to the risk of HIV-1 MTCT. A case-cohort study
      was conducted of 149 women randomly selected from a cohort of HIV-1-infected
      pregnant Malawians; these women served as a reference group for 36 cases of in
      utero MTCT and 43 cases of intrapartum (IP) MTCT. Cord PLAP activity was measured
      with an immunocatalytic assay. Infant HIV status was determined by real-time PCR.
      The association between cord PLAP activity and HIV-1 MTCT was measured with
      logistic regression using generalized estimating equations. Among vaginal
      deliveries, PLAP was associated with IP MTCT (risk ratio, 2.25 per log10 ng/ml
      PLAP; 95% confidence interval, 0.95-5.32) but not in utero MTCT. In a
      multivariable model adjusted for HIV-1 RNA load, chorioamnionitis, and self
      reported fever, the risk of IP MTCT almost tripled for every log10 increase in
      cord PLAP activity (risk ratio, 2.87; 95% confidence interval, 1.05-7.83).
      CONCLUSION: These results suggest that during vaginal deliveries, placental
      microtransfusions are a risk factor for IP HIV-1 MTCT. Future studies are needed
      to identify factors that increase the risk for microtransfusions in order to
      prevent IP HIV-1 MTCT.

PMID- 16287343
TI  - Force-time curve characteristics of dynamic and isometric muscle actions of elite
      women olympic weightlifters.
AB  - Six elite women weightlifters were tested to evaluate force-time curve
      characteristics and intercorrelations of isometric and dynamic muscle actions.
      Subjects performed isometric and dynamic mid-thigh clean pulls at 30% of maximal
      isometric peak force and 100 kg from a standardized position on a 61.0 x 121.9 cm
      AMTI forceplate. Isometric peak force showed strong correlations to the athletes'
      competitive snatch, clean and jerk, and combined total (r = 0.93, 0.64, and 0.80
      respectively). Isometric rate of force development showed moderate to strong
      relationships to the athletes' competitive snatch, clean and jerk, and combined
      total (r = 0.79, 0.69, and 0.80 respectively). The results of this study suggest
      that the ability to perform maximal snatch and clean and jerks shows some
      structural and functional foundation with the ability to generate high forces
      rapidly in elite women weightlifters.

PMID- 16287344
TI  - Effect of creatine phosphate supplementation on anaerobic working capacity and
      body weight after two and six days of loading in men and women.
AB  - The purpose of this study was to determine the effects of 2 and 6 days of
      creatine phosphate loading on anaerobic working capacity (AWC) and body weight
      (BW) in men and women. Sixty-one men (n = 31) and women (n = 30) randomly
      received 1 of 3 treatments (4 x 5 g.d(-1) x 6 days) using a double blind design:
      (a) 18 g dextrose as placebo (PL); (b) 5.0 g Cr + 20 g dextrose (Cr); or (c) 5.0
      g Cr + 18 g dextrose + 4 g of sodium and potassium phosphates (CrP). AWC was
      determined at baseline and following 2 and 6 days of supplementation using the
      Critical Power Test. BW increased significantly over time, and the mean value for
      the men was significantly greater compared to that for women, but there were no
      interactions (p > 0.05). There were gender-specific responses for AWC expressed
      in both absolute values (kJ) and relative to BW (kJ. kg(-1)), with the women
      demonstrating no significant interactions. For the men, CrP loading significantly
      increased AWC following 2 days (23.8%) and 6 days (49.8%) of supplementation vs.
      PL (kJ and kJ.kg(-1)). Cr supplementation increased AWC 13-15% in both genders
      compared to PL (1.1%- 3.0% decline); although this result was not statistically
      significant, it may have some practical significance.

PMID- 16287345
TI  - Physiological and anthropometric characteristics of junior rugby league players
      over a competitive season.
AB  - This study investigated the physiological and anthropometric characteristics of
      junior rugby league players over a competitive season. Forty-five rugby league
      players were allocated into training (n = 36) and nonexercise control (n = 9)
      groups. The training group participated in 2 field-training sessions each week
      with training loads, match loads, and injury rates recorded. Subjects performed
      measurements of standard anthropometry (height, body mass, and sum of 7
      skinfolds), muscular power (vertical jump), speed (10-, 20-, and 40-m sprint),
      agility ('L run'), and estimated maximal aerobic power (multi-stage fitness test)
      in December (off-season), March (preseason), May (midseason), and August (end
      season). Training loads progressively increased in the general preparatory phase
      of the season (preseason period), and declined slightly during the competitive
      phase of the season. Match intensity and match loads decreased throughout the
      season. Increases in estimated maximal aerobic power and muscular power and
      reductions in skinfold thickness occurred during the general preparatory phase of
      the season, and were maintained throughout the competitive phase of the season.
      These findings suggest that high training loads in the general preparatory phase
      of the season and low match loads in the competitive phase of the season allow
      junior rugby league players to maintain a high level of fitness throughout an
      entire competitive season.

PMID- 16287346
TI  - Neuromuscular performance characteristics of open-wheel and rally drivers.
AB  - The purpose of the present study was to investigate neuromuscular performance
      characteristics in open-wheel and rally drivers using the cross-sectional study
      design. The subjects (N = 28) consisted of experienced international-level open
      wheel drivers (n = 9), experienced international-level rally drivers (n = 9) and
      a physically active nondriving male control group (n = 10). In 3 separate test
      sessions, speed, muscle strength, and endurance tests were performed. The rally
      drivers had higher (p < 0.05) grip, shoulder flexion, and ankle plantar flexion
      strength, as compared to the control group. The open-wheel drivers showed higher
      strengths (p < 0.05) than the controls in neck forces, grip, shoulder flexion,
      and leg extension. The rally drivers were stronger (p < 0.05) than the open-wheel
      drivers in grip, plantar flexion, and trunk extension forces, whereas the open
      wheel drivers were stronger (p < 0.01) than the rally drivers in neck lateral
      flexions and extension forces. Thus, competitive long-term open-wheel and rally
      drivers differ specifically in neuromuscular performance. For practice, these
      findings suggest that rally drivers should concentrate on training hand, ankle,
      and trunk muscles, whereas open-wheel drivers should train neck muscles,
      especially, and all other muscle groups rather equally.

PMID- 16287347
TI  - Heart rate and blood lactate concentrations as predictors of physiological load
      on elite soccer players during various soccer training activities.
AB  - The purpose of this investigation was to estimate the physiologic strain on
      players during various soccer training activities. Ten soccer players from the
      first division soccer league of Turkey were used as subjects. The heart rate
      responses were measured during 4 types of soccer training. First, the heart rates
      that corresponded to a blood lactate concentration of both 2 and 4 mM were
      measured, and then, during the 4 types of training, they were correlated with the
      proportion of time that the heart rate was below the 2-mM lactate line, between
      the 2- and 4-mM lactate lines, and above the 4-mM lactate line. Mean heart rates
      during friendly match, modified game, tactical training, and technical training
      activities were 157 +/- 19, 135 +/- 28, 126 +/- 21, and 118 +/- 21 b.min(-1),
      respectively. The differences between all of these soccer training activities
      were statistically significant (p < or = 0.01). The results demonstrate that (a)
      technical and tactical training consisted of very low exercise intensities (most
      of the heart rates were below the 4-mM lactate level) and (b) the percentages of
      time that the heart rate correlated to a point above the 4-mM lactate reference
      level during the friendly match and modified game were 49.6 +/- 27.1% and 23.9 +/
      24.5%, respectively. The practical implications of these findings are that, by
      using 2- to 4-mM reference lines, coaches can structure heart rate zones that can
      help determine the individualized exercise intensity for their players as well as
      estimate overall exercise intensity during soccer training.

PMID- 16287348
TI  - Competitive-level differences in Yo-Yo intermittent recovery and twelve minute
      run test performance in soccer referees.
AB  - The aim of this study was to examine yo-yo intermittent recovery test (Yo-Yo
      test) and 12-minute run test (12MRT) performances in experienced soccer referees
      of different competitive levels. Three groups (n = 14 each) of experienced
      Italian soccer referees officiating in the first (series AB, top-level), third
      (series C, medium-level), and fourth (series D, low-level) division, were
      randomly submitted to the 12MRT and the Yo-Yo test during 2 testing sessions, 48
      hours apart. 12MRT performances were 3,000 +/- 112 m; 2,894 +/- 99 m; and 2,896
      +/- 171 m for top-level, medium-level and low-level referees, respectively (p >
      0.05). In the Yo-Yo test, the top-level, medium-level, and low-level referees
      covered 1,874 +/- 431 m; 1,360 +/- 172 m; and 1,272 +/- 215 m, respectively. The
      test performances of top-level referees in the Yo-Yo test was significantly
      different from those scored by medium-level and low-level referees (p < 0.05).
      After the Yo-Yo test, blood lactate concentrations (BLC) were higher in the
      medium-level and low-level referees compared with the top-level referees (p <
      0.05). The results of the present study show that the Yo-Yo test and not the
      12MRT can discriminate endurance performance in experienced elite level soccer
      referees. With respect to its discriminative and match performance validity, the
      Yo-Yo test may be considered a relevant field test to assess endurance
      preparedness for experienced soccer referees and a useful tool in talent
      selection.

PMID- 16287349
TI  - Comparison of loaded and unloaded jump squat training on strength/power
      performance in college football players.
AB  - The purpose of this study was to explore the effects of 5 weeks of eccentrically
      loaded and unloaded jump squat training in experienced resistance-trained
      athletes during the strength/ power phase of a 15-week periodized off-season
      resistance training program. Forty-seven male college football players were
      randomly assigned to 1 of 3 groups. One group performed the jump squat exercise
      using both concentric and eccentric phases of contraction (CE; n = 15). A second
      group performed the jump squat exercise using the concentric phase only (n = 16),
      and a third group did not perform the jump squat exercise and served as control
      (CT; n = 16). No significant differences between the groups were seen in power,
      vertical jump height, 40-yd sprint speed and agility performance. In addition, no
      differences between the groups were seen in integrated electromyography activity
      during the jump squat exercise. Significant differences between the CE and CT
      groups were seen in Delta 1RM squat (65.8 and 27.5 kg, respectively) and Delta
      1RM power clean (25.9 and 3.8 kg, respectively). No other between-group
      differences were observed. Results of this study provide evidence of the benefits
      of the jump squat exercise during a short-duration (5-week) training program for
      eliciting strength and power gains. In addition, the eccentric phase of this
      ballistic movement appears to have important implications for eliciting these
      strength gains in college football players during an off-season training program.
      Thus, coaches incorporating jump squats (using both concentric and eccentric
      phases of contraction) in the off-season training programs of their athletes can
      see significant performance improvements during a relatively short duration of
      training.

PMID- 16287350
TI  - Equipment and running surface alter sprint performance of college football
      players.
AB  - The purpose of this study was to determine the effect of football equipment and
      running surface on sprint performance in NCAA Division II football players (n =
      68). Players were timed in the 40-yd sprint on an indoor rubberized track (Day 1)
      and on an outdoor, natural-grass football field (Day 2) wearing either regulation
      football equipment or shorts and a T-shirt. Each player was assigned randomly to
      perform 2 trials under each condition on each surface, and the average of the 2
      trials was used for analysis. Offensive backs, defensive backs, and linebackers
      were significantly faster than were offensive and defensive linemen in all
      trials, and subjects were collapsed into 2 groups, backs and linemen. Football
      equipment significantly impaired performance on the track (-2.8% +/- 1.7%) and
      the field (-2.9% +/- 1.8%). The increase in body mass due to the football
      equipment was significantly greater for backs (7.2% +/- 0.7%) than for linemen
      (6.5% +/- 1.0%), but produced a significantly greater impairment in sprint
      performance in linemen (-3.3% +/- 1.1%) as compared with backs (-2.5% +/- 1.5%).
      Sprint performance was significantly and equivalently impaired when running on
      grass (backs: -2.5 +/- 1.1%; linemen: -2.8 +/- 1.4%) as compared with the track.
      Thus, running a 40-yd sprint in football equipment on a natural grass field
      impairs performance by an average of 5.5% (+/- 2.3%) compared with running
      indoors with minimal apparel. Football equipment and running surface
      significantly impair sprint performance in college football players, the effect
      being greater in linemen than in backs, and is likely related to differences in
      muscle strength/power and body fat.

PMID- 16287351
TI  - Combining explosive and high-resistance training improves performance in
      competitive cyclists.
AB  - In several recent studies, athletes experienced substantial gains in sprint and
      endurance performance when explosive training or high-intensity interval training
      was added in the noncompetitive phase of a season. Here we report the effect of
      combining these 2 types of training on performance in the competitive phase. We
      randomized 18 road cyclists to an experimental (n = 9) or control (n = 9) group
      for 4-5 weeks of training. The experimental group replaced part of their usual
      training with twelve 30-minute sessions consisting of 3 sets of explosive single
      leg jumps (20 for each leg) alternating with 3 sets of high-resistance cycling
      sprints (5 x 30 seconds at 60-70 min(-1) with 30-second recoveries between
      repetitions). Performance measures, obtained over 2-3 days on a cycle ergometer
      before and after the intervention, were mean power in a 1- and 4-km time trial,
      peak power in an incremental test, and lactate-profile power and oxygen cost
      determined from 2 fixed submaximal workloads. The control group showed little
      mean change in performance. Power output sampled in the training sprints of the
      experimental group indicated a plateau in the training effect after 8-12
      sessions. Relative to the control group, the mean changes (+/-90% confidence
      limits) in the experimental group were: 1-km power, 8.7% (+/-2.5%); 4-km power,
      8.1% (+/-4.1%); peak power, 6.8% (+/-3.6); lactate-profile power, 3.7% (+/-4.8%);
      and oxygen cost, -3.0% (+/-2.6%). Individual responses to the training were
      apparent only for 4-km and lactate-profile power (standard deviations of 2.5% and
      2.8%, respectively). The addition of explosive training and high-resistance
      interval training to the programs of already well-trained cyclists produces major
      gains in sprint and endurance performance, partly through improvements in
      exercise efficiency and anaerobic threshold.

PMID- 16287352
TI  - Effects of resistance training intensity, volume, and session format on the
      postexercise hypotensive response.
AB  - The effect of resistance exercise (RE) on the postexercise systolic and diastolic
      blood pressure (SBP and DBP) response in young men was investigated. Group 1 (G1)
      and group 2 (G2) performed three 6 repetition maximum (6RM) sets in a set
      repetition format for 5 and 6 exercises, respectively. G1 and G2 also performed a
      circuit and set repetition format session, respectively, using 50% of the 6RM for
      3 sets of 12 repetitions (12-repetition protocol). SBP and DBP were determined
      before and up to 60 minutes postexercise. G1's postexercise SBP demonstrated a
      significant decrease from its preexercise SBP, lasting 50 minutes after both RE
      sessions. G2's postexercise SBP demonstrated a significant difference from its
      preexercise SBP after the 6RM and 12-repetition protocol, lasting 60 and 40
      minutes, respectively. The only significant difference in the DBP from rest was
      at 10 minutes postexercise for G2 after the 12-repetition-per-set protocol. In
      summary, results indicate that RE intensity affects the duration, but not the
      magnitude, of the postexercise hypotensive response.

PMID- 16287353
TI  - The reliability of the FitroDyne as a measure of muscle power.
AB  - The FitroDyne is a device that attaches to conventional resistance-training
      equipment to measure speed of movement, from which muscle power is calculated.
      The aim of this study was to quantify the repeatability of the measurement of
      muscle power with the FitroDyne during squat jump and biceps curl exercises.
      Thirty male subjects completed 3 trials, each consisting of 6 squat jumps and 6
      biceps curls of increasing loads. Upper body and lower body maximum power was
      predicted from the force-velocity curves derived from the range of weights used
      for each trial. Maximum power measurements of a squat jump (range, 911- 1,673 W)
      and biceps curl (range, 45-110 W) had intraclass correlation coefficients (ICC)
      of R = 0.97 (95% CI, 0.95-0.98) and R = 0.97 (95% CI, 0.95-0.98), respectively.
      The limits of agreement for the squat jump and biceps curl trials were -17 +/- 96
      W and 0.11 +/- 13.90 W, respectively. It may be concluded that muscle power can
      be measured with a high degree of reliability with the FitroDyne. The limits of
      agreement need to be considered when data are interpreted.

PMID- 16287354
TI  - Influences of repetitive drop jump and isometric leg press exercises on tendon
      properties in knee extensors.
AB  - The present study aimed to investigate the effects of repetitive drop jumps (DJ)
      and isometric leg presses (LP) on the tendon properties in knee extensors. Before
      and after each endurance test, the elongation (L) of the tendon and aponeurosis
      of the vastus lateralis muscle was measured directly by ultrasonography while the
      subjects performed ramp isometric knee extensions up to maximum voluntary
      isometric contraction. Eight men performed 100 repetitions of the DJ and 50
      repetitions of the LP for 10 seconds with 10 seconds relaxation. In the DJ, there
      were no significant differences in L values at any force production levels before
      and after each endurance test. In LP, however, the L values above 500 N were
      significantly greater after the endurance test than before. These results suggest
      that the tendon properties in knee extensors change to become more compliant
      after the repeated longer-duration contractions, but not after repeated ballistic
      exercises.

PMID- 16287355
TI  - Reliability and validity of the modified Conconi test on concept II rowing
      ergometers.
AB  - The purpose of this study was to assess the reliability and validity of the
      modified Conconi test on Concept II rowing ergometers. Twenty-eight oarsmen
      conducted 3 performance tests on separate days. Reliability was assessed using
      the break point in heart rate (HR) linearity called the Conconi test (CT) and
      Conconi retest (CRT) for the noninvasive measurement of anaerobic threshold (AT).
      Blood lactate measurement was considered the gold standard for the assessment of
      the AT, and the validity of the CT was assessed by blood samples taken during an
      incremental load test (ILT) on ergometers. According to the results, the mean
      power output (PO) scores for the CT, CRT, and ILT were 234.2 +/- 40.3 W, 232.5 +/
      39.7 W, and 229.7 +/- 39.6 W, respectively. The mean HR values at the AT for the
      CT, CRT, and ILT were 165.4 +/- 11.2 b.min, 160.4 +/- 10.8 b.min, and 158.3 +/-
      8.8 b.min, respectively. Interclass correlation coefficient (ICC) analysis
      indicated a significant correlation between the 3 tests with one another. Also,
      Bland and Altman plots showed that there was an association between noninvasive
      tests and the ILT PO scores and HRs (95% confidence interval [CI]). In
      conclusion, this study showed that the modified CT is a reliable and valid method
      for determining the AT of elite men rowers.

PMID- 16287356
TI  - Effect of eccentric strength testing on delayed-onset muscle pain.
AB  - This investigation was designed to determine the effect of eccentric strength
      testing on delayed-onset muscle pain in 20 untrained university students.
      Initially, eccentric strength testing (5-repetition maximum [5RM]) was performed
      bilaterally. Next, 1 arm completed 3 sets of 10 eccentric repetitions to induce
      delayed-onset muscle pain. Then, in a subsequent session, whichever arm
      previously performed only the 5RM test completed the 5RM test a second time and
      the 3 sets of 10 eccentric repetitions. Statistical analyses supported
      significantly increased pain intensity and unpleasantness across 48 hours post
      5RM test alone. However, pain intensity and unpleasantness after the eccentric
      training bouts were significantly lower in the arm that performed 2 5RM tests
      than the arm that performed only 1. Thus, the eccentric strength testing produced
      delayed-onset muscle pain and protected against future delayed-onset muscle pain.
      These effects should be considered when such testing is used in baseline strength
      assessments.

PMID- 16287357
TI  - The acute effects of heavy-load squats and loaded countermovement jumps on sprint
      performance.
AB  - The purpose of this investigation was to determine whether performing high force
      or explosive force movements prior to sprinting would improve running speed.
      Fifteen NCAA Division III football players performed a heavy-load squat (HS),
      loaded countermovement jump (LCMJ), or control (C) warm-up condition in a
      counterbalanced randomized order over the course of 3 weeks. The HS protocol
      consisted of 1 set of 3 repetitions at 90% of the subject's 1 repetition maximum
      (1RM). The LCMJ protocol was 1 set of 3 repetitions at 30% of the subject's 1RM.
      At 4 minutes post-warm-up, subjects completed a timed 40-m dash with time
      measured at 10, 30, and 40 m. The results of the study indicated that when
      preceded by a set of HS, subjects ran 0.87% faster (p < or = 0.05) in the 40-m
      dash (5.35 +/- 0.32 vs. 5.30 +/- 0.34 seconds) in comparison to C. No significant
      differences were observed in the 10-m or 30-m split times between the 3
      conditions. The data from this study suggest that an acute bout of low-volume
      heavy lifting with the lower body may improve 40-m sprint times, but that loaded
      countermovement jumps appear to have no significant effect.

PMID- 16287358
TI  - Effect of loading on enhancement of power performance over three consecutive
      trials.
AB  - The acute effects of maximal voluntary isometric contractions (MVICs) in the
      squat position on subsequent measures of power output over 3 consecutive sets
      were investigated. Sixteen trained men experienced with back squats participated
      in the study. A 7-second MVIC was performed 4 minutes before the execution of 5
      maximal countermovement jumps (CMJs) and was repeated for 3 consecutive sets
      (protocol 1). The results were compared to power output performance in a similar
      protocol (protocol 2) that excluded the 7-second MVICs. No significant
      differences occurred in any of the power output measurements between protocol 1
      and protocol 2, nor did significance occur linearly across the 4 sets of CMJ,
      with the exception of a decrease in peak power in protocol 2 (p < or = 0.05).
      Using both mean and maximal values only one significant correlation between
      either relative strength and performance enhancement or absolute strength and
      performance enhancement was present at p < or = 0.01. At p < or = 0.05,
      significant correlations were found between absolute strength and mean peak power
      (PP), mean peak acceleration (PA), mean peak force (PF), max PP, max PA, max PF,
      and max peak velocity. These data indicate that the execution of an MVIC
      performed before a power exercise was inadequate to acutely enhance power output
      over any of 3 consecutive trials.

PMID- 16287359
TI  - The impact of seatback angle on electromyographical activity of the lower back
      and quadriceps muscles during bilateral knee extension.
AB  - This study investigated variations in electromyographic (EMG) responses of the
      erector spinae (ES), vastus medialis (VM), rectus femoris (RF), and vastus
      lateralis (VL) to different seatback angles during leg extension. Twenty men and
      women (10 men, 10 women; age 27.49 +/- 6.16 years) performed 8 repetitions at 70%
      of 8 repetition maximum at seatback angles of 1.57, 1.75, and 1.92 radius (rad).
      Analyses using repeated-measures analysis of variance indicated the greatest root
      square mean of the EMG (rmsEMG) and integrated EMG (intEMG) for the ES were at
      1.92 rad, and the greatest for the VM (concentric) and VL (eccentric) were at
      1.57 rad. No differences were observed among seat angles for the RF except for a
      higher normalized intEMG at 1.92 than 1.75 rad (concentric). Throughout all sets
      for all conditions and muscles, rmsEMG and intEMG significantly increased and
      median power frequency significantly decreased. These data indicate that a
      seatback angle of 1.57 rad is best for a leg extension machine, because this
      angle maximizes quadriceps activity while minimizing stress on the lower back
      muscles.

PMID- 16287360
TI  - Validation of an abdominal muscle strength test with dynamometry.
AB  - Adequate abdominal strength prevents work- and sports-related injuries and
      stabilizes the spine for athletic activities. The double-leg-lowering maneuver
      (DLLM) is a popular test to assess abdominal strength because of its simplicity;
      however, its validity and reliability have not been studied thoroughly. To
      determine the validity and reliability of the DLLM, 4 examiners evaluated 28
      subjects. The validity of the DLLM was evaluated with the Nicholas Hand-Held
      Dynamometer (NHHD) as the gold standard. The DLLM scores were compared to
      themselves for reliability and to NHHD scores for validity. Reliability for the
      DLLM was very high (r = 0.932). Validity of the DLLM was low (r = -0.338 to 
      0.446). The DLLM is reliable, but it has low validity to assess abdominal
      strength. The DLLM may be a useful tool to assess pelvic tilt motor control for
      spine stability, but it is not suitable for assessing muscle strength.

PMID- 16287361
TI  - Influence of playing position on the site, nature, and cause of rugby league
      injuries.
AB  - This study investigated the influence of playing position on the site, nature,
      and cause of injuries in rugby league. The incidence, site, nature, and cause of
      playing injuries was prospectively studied in 156 rugby league players over 2
      seasons. An injury was defined as any pain or disability suffered by a player
      during a match that resulted in the player missing a subsequent match. The hooker
      (101 per 1,000 playing hours) and prop (92 per 1,000 playing hours) positions had
      the highest incidence of injury. Injuries sustained by the fullback (32 per 1,000
      playing hours) and halfback (44 per 1,000 playing hours) positions were less
      common. Compared with other individual playing positions, props had a
      significantly higher incidence of overexertion injuries (22 per 1,000 playing
      hours), thigh and calf injuries (47 per 1,000 playing hours), and hematomas (19
      per 1,000 playing hours), whereas the five-eighth position (31 per 1,000 playing
      hours) and the hookers and halves positional group (17 per 1,000 playing hours)
      had a significantly higher incidence of falling and stumbling injuries. These
      results demonstrate that the hooker and prop positions have higher injury rates
      than other rugby league positions. Furthermore, the site, type, and cause of
      injuries are different among individual playing positions and playing groups.
      These findings suggest that individual position training for injury prevention is
      warranted in rugby league.

PMID- 16287362
TI  - Early strength response of the knee extensors during eight weeks of resistive
      training after unilateral total knee arthroplasty.
AB  - The purpose of this study was to document the early history of knee extensor
      torque production before and after total knee arthroplasty (TKA), explore the
      relationship between strength assessments, and describe an 8-week resistive
      training protocol. Thirty-eight individuals (19 men, 19 women) with unilateral
      TKA volunteered to participate in this repeated-measures study. For this group,
      the mean age was 72.23 +/- 5.34 years; height was 168.00 +/- 8.57 cm; and weight
      was 79.42 +/- 14.57 kg. Torque production of the knee extensors was assessed
      isokinetically at 60 and 180 degrees .s(-1) before surgery, 30 days after
      unilateral TKA (+30), and 60 days after unilateral TKA (+60). Torque production
      was significantly different between limbs at both 60 and 180 degrees .s(-1) (p <
      0.0125) before surgery. Torque production was lower at +30 compared with before
      surgery at both 60 and 180 degrees .s(-1) (p < 0.002). By +60, torque production
      was greater than at +30 at both 60 and 180 degrees .s(-1) (p < 0.002).

PMID- 16287363
TI  - Design of a controlled-release ergometer for the measurement of musculotendinous
      stiffness of the knee flexors.
AB  - The stiffness of muscle-tendon units (MTUs) influences many aspects of human
      movement from athletic performance to injury risk. Presently the controlled
      release technique of measuring MTU stiffness has been applied almost exclusively
      to the distal joints of the body, i.e., the ankle. This is primarily because of
      the mechanical limitations of implementing this technique. However, in order to
      better understand how the elastic properties of the MTU affect both performance
      and injury potential, measurements of MTU stiffness of the more proximal joints
      must be made. The knee flexors are a logical choice because of the integral role
      of MTU stiffness of this muscle group in both hamstring strains and knee injury.
      The purpose of this study was to modify a commercial ergometer so that it could
      be used to measure the musculotendinous stiffness of the knee flexors. Data are
      presented for a representative participant to illustrate the feasibility and
      capability of this ergometer, and the measured MTU stiffness was 519 N.m.rad(-1)
      at a knee flexion moment of 100 N.m. Our results indicate that it is indeed
      possible to modify a commercial ergometer and measure musculotendinous stiffness
      of large muscle groups crossing proximal joints.

PMID- 16287364
TI  - The carnosine content of vastus lateralis is elevated in resistance-trained
      bodybuilders.
AB  - Resistance training is associated with periods of acute intracellular hypoxia
      with increased H(+) production and low intramuscular pH. The aim of this study
      was to investigate the possible adaptive response in muscle carnosine (beta
      alanyl-L-histidine) in bodybuilders. Extracts of biopsies of m. vastus lateralis
      of 6 national-level competitive bodybuilders and 6 age-matched untrained but
      moderately active healthy subjects were analyzed by high-performance liquid
      chromatography. Significant differences were shown in carnosine (p < 0.001) and
      histidine (p < 0.05). Muscle carnosine in bodybuilders was twice that in
      controls. The carnosine contents measured are the highest recorded in human
      muscle and represent a 20% contribution to muscle buffering capacity. Taurine was
      38% lower in bodybuilders, though the difference was not significant. Possible
      causes for the changes observed are prolonged repetitive exposure to low muscle
      pH, change of diet or dietary supplement use, or the use of anabolic steroids.
      The increase in buffering capacity could influence the ability to carry out
      intense muscular activity.

PMID- 16287365
TI  - Is running performance enhanced with creatine serum ingestion?
AB  - Runners Advantage (RA) creatine (Cr) serum has been marketed to increase running
      performance. To test this claim, cross-country runners completed baseline testing
      (BASE), an outdoor 5,000-m run followed by treadmill Vo(2)max testing on the same
      day. Subjects repeated testing after ingesting 5 ml of RA (n = 13) containing 2.5
      g of Cr or placebo (n = 11). Heart rate (HR), rating of perceived exertion (RPE),
      and run time were recorded. With RA (56.48 +/- 8.93 ml.kg(-1.)min(-1)), Vo(2)max
      was higher (p = 0.01) vs. BASE (54.07 +/- 9.36 ml.kg(-1.)min(-1)), yet the
      magnitude of the increase was within the coefficient of variation of Vo(2)max. No
      effect of RA on maximal HR was exhibited, yet Vco(2)max and duration of
      incremental exercise were significantly higher (p < 0.025) vs. BASE. Vo(2)max was
      similar in PL (58.85 +/- 6.67 ml.kg(-1).min(-1)) and BASE (57.28 +/- 7.22 ml.kg(
      1.)min(-1)). With RA, the 5,000-m time was unchanged, and RPE was lower (p <
      0.025) vs. BASE. These data do not support the ergogenic claims of RA in its
      current form and dose.

PMID- 16287367
TI  - Blood lactate and metabolic responses to controlled frequency breathing during
      graded swimming.
AB  - Controlled frequency breathing (CFB) is a training technique used by swimmers in
      an effort to simulate high-intensity workloads by limiting oxygen availability to
      the body and stimulating anaerobic metabolism. During CFB, a swimmer voluntarily
      restricts breathing, which, theoretically, limits oxygen availability and
      stimulates anaerobic metabolism. The purpose of this study was to determine the
      influence of CFB on blood lactate and metabolic responses during graded increases
      in swimming intensity. A free swimming (FS) protocol was used to determine blood
      lactate and heart rate (HR) responses to CFB, while a tethered swimming (TS)
      protocol was used to determine blood lactate, HR, and ventilatory responses to
      CFB. The subjects swam four 3-minute trials at workloads of 55, 65, 75, and 85%
      of peak intensity during both protocols. A total of 46 competitive collegiate
      swimmers participated in the study. Thirty-four subjects (14 men and 20 women)
      completed the FS protocol, and 12 subjects (7 men and 5 women) completed the TS
      protocol. CFB reduced ventilation and Vo(2) (p < 0.05) during the TS protocol and
      reduced HR (p < 0.05) during the FS protocol when compared to normal breathing.
      However, CFB did not alter blood lactate concentrations for either protocol (p >
      0.05). Our findings demonstrate that although CFB does not alter the blood
      lactate response to graded increases in swimming intensity, it appears to reduce
      the ventilatory and HR responses to exercise. Thus, swim coaches can use CFB at
      moderate intensities to simulate high-intensity training but should consider
      adjusting HR training zones to reflect the reduction in HR associated with
      reduced ventilation.

PMID- 16287366
TI  - Effect of a defined lacto-ovo-vegetarian diet and oral creatine monohydrate
      supplementation on plasma creatine concentration.
AB  - This study examined the effects that preceding creatine supplementation with a
      lacto-ovo-vegetarian diet would have on plasma creatine concentration. Twenty-six
      healthy moderately fit omnivorous men were assigned to either a 26-day lacto-ovo
      vegetarian (LOV; n = 12) or omnivorous (Omni; n = 14) diet. On day 22, subjects
      were also assigned in a double-blind manner either creatine monohydrate (CM; 0.3
      g.kg(-1).day(-1) + 20 g Polycose) or an equivalent dose of placebo (PL) for 5
      days. Blood samples were taken on days 1, 22 and 27. Consuming a LOV diet for 21
      days was effective in reducing plasma creatine concentration (p < 0.01) in the
      LOV group. Regardless of diet, the CM group showed an increase in plasma creatine
      concentrations from day 22 to 27, whereas the PL group's levels remained the same
      (p < 0.05). Although the LOV diet caused a deprivation effect in plasma creatine
      concentration relative to the Omni diet, concurrent supplementation with creatine
      resulted in no difference in plasma creatine concentrations between the LOV and
      Omni diet groups. Dietary advice should be provided to LOV athletes that
      supplementation with creatine may help to increase their muscle stores of
      creatine, and thus their ATP resynthesis capabilities, to levels similar to those
      of omnivores.

PMID- 16287368
TI  - Age-related effects on fitness performance in elite-level soccer referees.
AB  - Elite soccer referees usually achieve the peak of their officiating careers at an
      average age that is considerably older than that observed in competitive matched
      soccer players. As ageing has been reported to negatively affect physical
      performance, the aim of this study was to investigate the effect of ageing on
      fitness performance in elite-level soccer referees. Thirty-six elite-level soccer
      referees were grouped into young (Y, n = 12), average (A, n = 14), and old (O, n
      = 10) groups, according to their age and observed for field test performance
      (countermovement jump [CMJ], 50-m and 200-m sprints, and 12-minute running for
      distance). Results showed a significant age effect on CMJ (r = -0.52, p < 0.001),
      200 m (r = 0.51, p < 0.001), and 12-minute time trial running (r = -0.52, p <
      0.001). Y jumped higher than A and O groups (p < 0.05) and were faster than O
      over 200 m (p < 0.05). No group effect was observed for 12-minute run and 50-m
      performance (p > 0.05), respectively. Sixteen of the 36 referees were further
      examined for selected physiological variables and grouped into 2 equal (n = 8)
      age groups (young and old, Y1 and O1, respectively). Vo(2)max was higher in Y1 (p
      < 0.05), but O1 attained performances similar to Y1 running at selected blood
      lactate speeds (4 mmol L(-1), p > 0.05). Although older referees demonstrated
      acceptable fitness levels, younger officials should ensure that they develop
      appropriate levels of aerobic and anaerobic fitness to be able to match the
      demands placed upon them while refereeing throughout their careers. To promote
      this, fitness test standards should be age related.

PMID- 16287369
TI  - A comparison of scholastic and collegiate longsnapping techniques.
AB  - The purpose of this study was to identify the differences that exist between
      collegiate (CS) and scholastic (SS) longsnappers. Six CS (21.4 +/- 1.37 years)
      and 7 SS (16.7 +/- 1.11 years) longsnappers were filmed performing 10 longsnaps
      each. The CS and SS longsnappers had 7.0 +/- 0.89 and 2.7 +/- 0.95 years
      experience longsnapping, respectively. Each of the 10 longsnaps for all subjects
      were analyzed for takeoff velocity and accuracy. The snap that most closely
      approximated the individual snapper's median values for takeoff velocity and
      accuracy was digitized using a 20-point model. CS were both faster (0.85 +/- 0.10
      seconds vs. 1.25 +/- 0.19 seconds) and more accurate in terms of mean radial
      error (29.36 +/- 8.4 cm vs. 47.2 +/- 8.26 cm) than their SS counterparts. These
      differences were related to body positioning both before and during the longsnap.
      CS exhibited more shoulder flexion (135 +/- 6.33 degrees ; vs. 98 +/- 9.01
      degrees ) and greater elbow extension (133 +/- 8.1 degrees vs. 95 +/- 6.77
      degrees ) in the set position phase, along with greater center of mass movement
      (0.27 +/- 0.02 m vs. 0.14 +/- 0.04 m) in the anterior-posterior direction and
      less hip flexion (72 +/- 1.85 degrees vs. 49 +/- 9.42 degrees ) during the
      preflight phase. Longsnapping experience and accuracy were significantly related
      (r = -0.82, p < 0.05). These results suggest that body positioning both before
      and during the longsnap motion significantly influence the velocity and accuracy
      of the longsnap.

PMID- 16287371
TI  - Influence of contraction velocity in untrained individuals over the initial early
      phase of resistance training.
AB  - The purpose of this study was to determine the early phase adaptations in short
      term traditional (TRT) versus superslow (SST) resistance training. Sixteen
      apparently healthy subjects participated in this study. Subjects were pretested
      and posttested for their 1 repetition maximums (1RM) in the squat and bench
      press, peak power in a countermovement jump (CMJ) and squat jump (SJ), and body
      composition using dual energy x-ray absorptiometry. Subjects participated in an 8
      week resistance training program in either SST (n = 9, 3 men, 6 women), using 50%
      of 1RM, or TRT (n = 7, 3 men, 4 women), using 80% of 1RM. Both groups trained 3
      days per week. The TRT and SST groups improved in strength by 6.8 and 3.6% in the
      squat exercise and by 8.6 and 9.1% in the bench press, respectively. Peak power
      for the CMJ increased significantly in the TRT group, from 23.0 +/- 5.5 W/kg to
      25.0 +/- 6.3 W/kg; no such increase was seen with respect to the SST group. Both
      groups' 1RM increased significantly for both the bench press and the squat. No
      changes in body composition were seen for either group. The results of this study
      suggest that TRT is more effective for improving peak power than SST.

PMID- 16287370
TI  - Energy cost of moderate-duration resistance and aerobic exercise.
AB  - The purpose of this study was to compare energy expenditure of resistance and
      aerobic exercise matched for total time and relative intensity. Ten trained men
      (24.3 +/- 3.8 years) performed 30 minutes of intermittent free-weight squatting
      at 70% of 1 repetition maximum and continuous cycling at 70% of Vo(2)max, in a
      crossover design. Vo(2), kilocalories (kcal), work, respiratory exchange ratio
      (RER), V(E), heart rate (HR), and rating of perceived exertion (RPE) data were
      recorded. Cycling resulted in greater total Vo(2) (87 +/- 3 vs. 53 +/- 3 L, mean
      +/- SEM), kcal expenditure (441 +/- 17 vs. 269 +/- 13), and work (335 +/- 11 vs.
      128 +/- 11 kJ) than squatting did. The mean RER was greater during squatting
      (1.03 +/- 0.01 vs. 0.94 +/- 0.01), and the V(E) values were greater during
      cycling (82 +/- 3 vs. 70 +/- 3 L.min(-1)). The HR response was nearly identical
      between exercise modes (160 +/- 5 vs. 160 +/- 4 bpm), whereas the RPE was greater
      during squatting (16.96 +/- 0.41 vs. 14.88 +/- 0.42). These data suggest that
      although lower than similarly matched aerobic exercise, resistance exercise
      resulted in an energy cost that would meet the recommendations for kcal
      expenditure as suggested by the American College of Sports Medicine, if performed
      4-5 days per week. These findings should be considered by coaches and trainers
      working with individuals mutually interested in muscular development and weight
      management, because programs of structured resistance exercise may assist with
      both.

PMID- 16287372
TI  - Carbohydrate supplementation and perceived exertion during resistance exercise.
AB  - The purpose of the present study was to investigate the relationship between
      carbohydrate energy substrate and the perception of exertion during resistance
      exercise. Thirty strength-trained subjects were randomized to a carbohydrate
      group (C) or a placebo group (P), and lifted weights for 2 hours (4 sets; 10
      repetitions maximum; 10 exercises; 2-3-minute rest intervals). Subjects ingested
      10 ml.kg(-1).h(-1) of 6% carbohydrate or placebo beverages during the resistance
      training bout. The 15-category Borg Perceived Exertion Scale was used to assess
      overall body (RPE-O) and active muscle (RPE-AM) perceived exertion after
      completion of the last repetition in each set for each exercise. No significant
      differences were found between the C and P groups for either RPE-O or RPE-AM,
      with the exception of RPE-O for the upright row and back squat (p < 0.05).
      Carbohydrate supplementation exerted no attenuating effect on ratings of
      perceived exertion (RPE) during resistance training.

PMID- 16287374
TI  - Comparison of two twelve week off-season combined training programs on entry
      level collegiate soccer players' performance.
AB  - Olympic-style lifts (OSL) and plyometric exercises (PE) are frequently combined
      with traditional resistance training (TRT) to improve athletic performance. The
      goal of this study was to directly compare the performance effect of TRT (30
      minutes) combined with either OSL or nondepth-jump PE (15 minutes) on entry level
      competitive collegiate athletes. Ten female and 5 male competitive soccer
      players, divided into 2 groups, completed 12 weeks of tri-weekly training during
      their off-season. Countermovement vertical jump, 4 repetition maximum squat, 25-m
      sprint, and figure-8 drill on a 5-dot mat were conducted pre-, mid-, and
      postintervention. Significant improvements were made by both groups in each
      performance parameter over the 12-week period (p < 0.05), with no significant
      differences found between the training groups. Although these training modalities
      may achieve their results through slightly different mechanisms, the performance
      related improvements may not be significantly different for entry-level
      collegiate athletes with little resistance training experience.

PMID- 16287373
TI  - Applications of the dose-response for muscular strength development: a review of
      meta-analytic efficacy and reliability for designing training prescription.
AB  - There has been a proliferation in recent scholarly discussion regarding the
      scientific validity of single vs. multiple sets of resistance training (dose) to
      optimize muscular strength development (response). Recent meta-analytical
      research indicates that there exist distinct muscular adaptations, and dose
      response relationships, that correspond to certain populations. It seems that
      training status influences the requisite doses as well as the potential magnitude
      of response. Specifically, for individuals seeking to experience muscular
      strength development beyond that of general health, an increase in resistance
      training dosage must accompany increases in training experience. The purpose of
      this document is to analyze and apply the findings of 2 meta-analytical
      investigations that identified dose-response relationships for 3 populations:
      previously untrained, recreationally trained, and athlete; and thereby reveal
      distinct, quantified, dose-response trends for each population segment. Two meta
      analytical investigations, consisting of 177 studies and 1,803 effect sizes (ES)
      were examined to extract the dose-response continuums for intensity, frequency,
      volume of training, and the resultant strength increases, specific to each
      population. ES data demonstrate unique dose-response relationships per
      population. For untrained individuals, maximal strength gains are elicited at a
      mean training intensity of 60% of 1 repetition maximum (1RM), 3 days per week,
      and with a mean training volume of 4 sets per muscle group. Recreationally
      trained nonathletes exhibit maximal strength gains with a mean training intensity
      of 80% of 1RM, 2 days per week, and a mean volume of 4 sets. For athlete
      populations, maximal strength gains are elicited at a mean training intensity of
      85% of 1RM, 2 days per week, and with a mean training volume of 8 sets per muscle
      group. These meta-analyses demonstrate that the effort-to-benefit ratio is
      different for untrained, recreationally trained, and athlete populations; thus,
      emphasizing the necessity of appropriate exercise prescription to optimize
      training effect. Exercise professionals may apply these dose-response trends to
      prescribe appropriate, goal-oriented training programs.

PMID- 16287375
TI  - Using a logarithmic regression to identify the heart-rate threshold in cyclists.
AB  - The purpose of this study was to establish an objective method for identifying
      the heart-rate threshold (HRT) in cyclists. Fifty-six male cyclists were tested
      on a cycle ergometer to volitional fatigue. Identification of the HRT used a
      heart-rate increase above a logarithmic regression line of best fit, coupled with
      the crossover of a linear regression line of best fit. The measures of Vco(2) and
      blood lactate for ventilatory threshold (VT) and lactate threshold (HLaT),
      respectively, were used as criterion measures to validate the HRT. Comparison of
      HRT with VT and HLaT showed significant associations (r = 0.98). Statistical
      variance between HRT, VT, and HLaT indicated no difference. From these findings,
      the logarithmic regression method provides an objective means to determine the
      HRT. Through this method, cyclists may obtain information for establishing
      accurate training levels and protocols.

PMID- 16287376
TI  - Proposed tests for measuring the running velocity at the oxygen consumption and
      heart rate thresholds for treadmill exercise.
AB  - The purposes of this study were to (a) determine if the mathematical model used
      to estimate the physical working capacity at the oxygen consumption threshold
      (PWC(VO(2))) and physical working capacity at the heart rate threshold (PWC(HRT))
      for cycle ergometry could be applied to treadmill running; (b) propose new
      fatigue thresholds called the running velocity at the oxygen uptake threshold
      (RV(VO(2))) and running velocity at the heart rate threshold (RV(HRT)) for
      treadmill exercise; and (c) statistically compare the velocities at the
      RV(VO(2)), RV(HRT), and ventilatory threshold (VT). Seven aerobically trained
      adult volunteers (mean +/- SD: age 24.0 +/- 3.9 years, Vo(2) max 56.7 +/- 7.1
      ml.kg(-1).min(-1)) performed a maximal treadmill test to determine Vo(2) peak and
      VT as well as four 8-minute submaximal workbouts for the determination of
      RV(VO(2)) and RV(HRT). One-way repeated-measures analysis of variance indicated
      that there were no significant (p > 0.05) mean differences among the running
      velocities for the RV(VO(2)), RV(HRT), and VT. The results of this study
      indicated that the mathematical model used to estimate PWC(VO(2)) and PWC(HRT)
      for cycle ergometry could be applied to treadmill running. Furthermore, the
      RV(VO(2)) and RV(HRT) test may provide submaximal techniques for estimating the
      VT.

PMID- 16287377
TI  - Effects of pelvic stabilization on lumbar muscle activity during dynamic
      exercise.
AB  - Many commonly utilized low-back exercise devices offer mechanisms to stabilize
      the pelvis and to isolate the lumbar spine, but the value of these mechanisms
      remains unclear. The purpose of this study was to examine the effect of pelvic
      stabilization on the activity of the lumbar and hip extensor muscles during
      dynamic back extension exercise. Fifteen volunteers in good general health
      performed dynamic extension exercise in a seated upright position on a lumbar
      extension machine with and without pelvic stabilization. During exercise, surface
      electromyographic activity of the lumbar multifidus and biceps femoris was
      recorded. The activity of the multifidus was 51% greater during the stabilized
      condition, whereas there was no difference in the activity of the biceps femoris
      between conditions. This study demonstrates that pelvic stabilization enhances
      lumbar muscle recruitment during dynamic exercise on machines. Exercise
      specialists can use these data when designing exercise programs to develop low
      back strength.

PMID- 16287378
TI  - Introduction to the special section on multicultural and community psychology:
      clinical psychology in context.
AB  - Human behavior occurs in the contexts of culture and community. Yet, clinical
      psychology has traditionally focused on the individual, neglecting the
      individual's context. The purpose of this Special Section is to address the
      underlying conceptual issues in integrating multicultural and community
      psychology within a common framework. The integration of etic and emic approaches
      distinguishes the research programs in these articles from others that have
      solely focused on universal or culture-specific approaches. Issues facing ethnic
      minority populations are addressed, including identification of risk and
      protective factors, obstacles to mental health service use, and optimal treatment
      effectiveness. The integration of culture and community contexts into clinical
      psychology is necessary for it to remain relevant in an increasingly diverse 21st
      century.

PMID- 16287379
TI  - Toward evidence-based interventions for diverse populations: The San Francisco
      General Hospital prevention and treatment manuals.
AB  - Clinical trials have seldom included adequate samples of people of color.
      Therefore, practitioners serving ethnic minorities often do not have access to
      readily available evidence-based interventions. This article summarizes the
      development and empirical evaluation of prevention and treatment manuals designed
      for low-income ethnic minority populations at San Francisco General Hospital. The
      manuals were often designed by people of color familiar with the communities for
      which they were developed. Independent research teams in multi-site national and
      international clinical trials have evaluated many of these manuals with
      encouraging results.

PMID- 16287380
TI  - Why bother with beliefs? Examining relationships between race/ethnicity, parental
      beliefs about causes of child problems, and mental health service use.
AB  - In this study, the authors examined the role of parental beliefs about the causes
      of child problems in predicting later mental health service use in a large,
      diverse population of at-risk youths. Study hypotheses were that parental beliefs
      consistent with biopsychosocial causes would be associated with later mental
      health service use; sociological, spiritual, or nature disharmony etiologies
      would be negatively associated with service use; and beliefs would partially
      mediate the relationship between race/ethnicity and service use. Of the 5
      biopsychosocial beliefs, 2 were positively related to later mental health service
      use. Unexpectedly, of the 6 parental beliefs related to sociological, spiritual,
      or nature disharmony etiologies, only 1 was negatively associated with later
      service use patterns. Parental endorsement of etiologies relating to physical
      causes, relational issues, trauma, and prejudice was found to partially mediate
      the relationship between race/ethnicity and service use for Asian/Pacific
      Islander American and Latino youths. ((c) 2005 APA, all rights reserved).

PMID- 16287381
TI  - Caregiver-therapist ethnic similarity predicts youth outcomes from an empirically
      based treatment.
AB  - The effects of caregiver-therapist ethnic similarity on youth outcomes from
      multisystemic therapy (MST), as implemented in dissemination sites, were
      examined. Consistent with hypotheses, findings confirmed that youths whose
      caregivers were ethnically matched with their therapists demonstrated greater
      decreases in symptoms, longer times in treatment, and increased likelihood of
      discharge for meeting treatment goals relative to youths whose caregivers and
      therapists were not ethnically matched. In addition, for youths whose caregivers
      were of mixed ethnic heritage, caregiver-therapist ethnic match was associated
      with greater improvements in psychosocial functioning. Ethnic match effects on
      both treatment length and discharge success were partially mediated by therapist
      adherence to MST. This study shows the importance of examining the effects of
      both client and therapist ethnicity on outcomes from empirically based
      treatments.

PMID- 16287382
TI  - Obstacles for rural American Indians seeking alcohol, drug, or mental health
      treatment.
AB  - The purpose of this study was to identify factors associated with 4 clusters of
      obstacles (self-reliance, privacy issues, quality of care, and communication and
      trust) to mental health and substance abuse treatment in 3 treatment sectors for
      residents of 3 reservations in the United States. Participants (N=3,084)
      disclosed whether they had sought treatment for emotional, drug, or alcohol
      problems in the past year and, if so, whether they had faced obstacles in
      obtaining care from Indian Health Services, tribal services, and other public or
      private systems. Correlates of these obstacles included negative social support,
      instrumental social support, utility of counselors, utility of family doctors,
      treatment sector, treatment type, diagnosis of an anxiety disorder, and tribe.

PMID- 16287383
TI  - Ethnicity, culture, and sexual aggression: risk and protective factors.
AB  - Explanatory models of sexual aggression were examined among mainland Asian
      American (n=222), Hawaiian Asian American (n=127), and European American men
      (n=399). The Malamuth et al. (N. M. Malamuth, D. Linz, C. L. Heavey, G. Barnes, &
      M. Acker, 1995; N. M. Malamuth, R. J. Sockloskie, M. P. Koss, & J. S. Tanaka,
      1991) confluence model of sexual aggression, which posits impersonal sex and
      hostile masculinity as paths to sexual aggression, was consistently supported.
      Culture-specific moderators of sexual aggression were also identified. Whereas
      loss of face was a protective factor against sexual aggression in the Asian
      American samples, it generally was not a protective factor among European
      Americans. These findings are not a function of actual or perceived minority
      status. An implication is that theoretical models may need to be augmented with
      cultural constructs for optimal application in certain ethnic group contexts.

PMID- 16287384
TI  - Effects of culturally adapted parent management training on Latino youth
      behavioral health outcomes.
AB  - A randomized experimental test of the implementation feasibility and the efficacy
      of a culturally adapted Parent Management Training intervention was conducted
      with a sample of 73 Spanish-speaking Latino parents with middle-school-aged youth
      at risk for problem behaviors. Intervention feasibility was evaluated through
      weekly parent satisfaction ratings, intervention participation and attendance,
      and overall program satisfaction. Intervention effects were evaluated by
      examining changes in parenting and youth adjustment for the intervention and
      control groups between baseline and intervention termination approximately 5
      months later. Findings provided strong evidence for the feasibility of delivering
      the intervention in a larger community context. The intervention produced
      benefits in both parenting outcomes (i.e., general parenting, skill
      encouragement, overall effective parenting) and youth outcomes (i.e., aggression,
      externalizing, likelihood of smoking and use of alcohol, marijuana, and other
      drugs). Differential effects of the intervention were based on youth nativity
      status.

PMID- 16287385
TI  - A new tool to assess treatment fidelity and evaluation of treatment fidelity
      across 10 years of health behavior research.
AB  - A. Bellg, B. Borrelli, et al. (2004) previously developed a framework that
      consisted of strategies to enhance treatment fidelity of health behavior
      interventions. The present study used this framework to (a) develop a measure of
      treatment fidelity and (b) use the measure to evaluate treatment fidelity in
      articles published in 5 journals over 10 years. Three hundred forty-two articles
      met inclusion criteria; 22% reported strategies to maintain provider skills, 27%
      reported checking adherence to protocol, 35% reported using a treatment manual,
      54% reported using none of these strategies, and 12% reported using all 3
      strategies. The mean proportion adherence to treatment fidelity strategies was
      .55; 15.5% of articles achieved greater than or equal to .80. This tool may be
      useful for researchers, grant reviewers, and editors planning and evaluating
      trials.

PMID- 16287386
TI  - Emotional arousal, client perceptual processing, and the working alliance in
      experiential psychotherapy for depression.
AB  - Early-, middle-, and late-phase client emotional arousal, perceptual processing
      strategies, and working alliance were examined in relation to treatment outcome
      on 4 measures in 32 clients who previously underwent experiential therapy for
      depression. Hierarchical regression analyses relating these variables to outcome
      indicated that results varied depending on the therapeutic process, phase of
      treatment, and outcome measure involved in the analyses. Mid-therapy arousal
      predicted improvements in self-esteem, whereas mid- and late treatment perceptual
      processing predicted reductions in client interpersonal dysfunction. Emotional
      arousal in conjunction with perceptual processing during mid-therapy predicted
      reductions in depressive and psychopathological symptomatology better than either
      of these variables alone. The implications of these findings for psychotherapy
      research and practice are discussed.

PMID- 16287387
TI  - Randomized controlled trial of a brief intervention for increasing participation
      in parent management training.
AB  - Evidence-based treatments exist for a range of child and adolescent behavior
      problems; however, effects are often limited by poor treatment attendance and
      adherence. The authors developed and evaluated the efficacy of a brief (5 to 45
      min) intervention designed to increase treatment attendance and adherence in a
      sample of 76 parents referred for treatment of their child's oppositional,
      aggressive, and antisocial behavior. The results of this randomized controlled
      trial showed that parents who received this brief intervention had greater
      treatment motivation, attended significantly more treatment sessions, and had
      greater adherence to treatment according to both parent and therapist report.
      This study provides researchers and clinicians with a brief and efficacious
      method of increasing motivation, attendance, and adherence for treatment.

PMID- 16287388
TI  - Can group interventions facilitate forgiveness of an ex-spouse? A randomized
      clinical trial.
AB  - This study evaluated the effectiveness of 2 versions of an 8-session forgiveness
      group intervention for divorced individuals. Participants (randomized, n=192;
      analyzed, n=149) were randomly assigned to a secular forgiveness condition, a
      religious forgiveness condition, or a no-intervention comparison condition.
      Measures of forgiveness and mental health were obtained at pretest, posttest, and
      6-week follow-up. Participants in both intervention conditions increased
      significantly more than comparison participants on self-reported forgiveness of
      an ex-spouse and understanding of forgiveness. Participants in the secular
      condition showed a greater decrease in depressive symptoms than comparison
      participants. Intrinsic religiousness did not moderate intervention effects.

PMID- 16287389
TI  - Prediction of response to treatment in a randomized clinical trial of marital
      therapy.
AB  - This study investigated demographic, intrapersonal, and interpersonal predictors
      of treatment response in a randomized clinical trial of 134 distressed married
      couples, which examined traditional (N. S. Jacobson & G. Margolin, 1979) and
      integrative (N. S. Jacobson & A. Christensen, 1996) behavioral couple therapy.
      Results based on hierarchical linear modeling revealed that interpersonal
      variables were the strongest predictors, but their effects were largely limited
      to predicting initial marital dissatisfaction; greater individual mental health
      was also associated with less distress initially. Couples who were married longer
      demonstrated stronger treatment gains, and exploratory analyses suggested that
      sexually dissatisfied couples showed slower initial, but overall more consistent,
      gains in the integrative versus the traditional approach. Findings are considered
      in light of the previous literature on predicting response to marital therapy.

PMID- 16287390
TI  - Predicting change for individual psychotherapy clients on the basis of their
      nearest neighbors.
AB  - This study extended client-focused research by using the nearest neighbor (NN)
      approach, a client-specific sampling and prediction strategy derived from
      research on alpine avalanches. Psychotherapy clients (N=203) seen in routine
      practice settings in the United Kingdom completed a battery of intake measures
      and then completed symptom intensity ratings before each session. Forecasts of
      each client's rate of change and session-by-session variability were computed on
      the basis of that client's NNs (n=10-50 in different comparisons). Alternative
      forecasts used linear or log-linear slopes and were compared with an alternative
      prediction strategy. Results showed that the NN approach was superior to the
      alternative model in predicting rate of change, though the advantage was less
      clear for predicting variability.

PMID- 16287391
TI  - Estimating variability in outcomes attributable to therapists: a naturalistic
      study of outcomes in managed care.
AB  - To estimate the variability in outcomes attributable to therapists in clinical
      practice, the authors analyzed the outcomes of 6,146 patients seen by
      approximately 581 therapists in the context of managed care. For this analysis,
      the authors used multilevel statistical procedures, in which therapists were
      treated as a random factor. When the initial level of severity was taken into
      account, about 5% of the variation in outcomes was due to therapists. Patient
      age, gender, and diagnosis as well as therapist age, gender, experience, and
      professional degree accounted for little of the variability in outcomes among
      therapists. Whether or not patients were receiving psychotropic medication
      concurrently with psychotherapy did affect therapist variability. However, the
      patients of the more effective therapists received more benefit from medication
      than did the patients of less effective therapists.

PMID- 16287393
TI  - Influences of beliefs and personality disorders on treatment outcome in anxiety
      patients.
AB  - The present study investigated the effects of personality disorders (PDs) and
      specific PD-related beliefs on the results of (cognitive-)behavioral therapy for
      anxiety disorders in a sample of 398 outpatients. The authors used a prospective
      design in which relationships between PD variables before treatment and outcome
      measures at posttest and follow-up were evaluated with multilevel analyses.
      People with PDs and PD-related beliefs reported higher symptom levels at outcome.
      However, these effects were not as strong as might be expected on the basis of
      prevailing clinical thought in this area. Dropout rates were not influenced by
      the presence of 1 or more PDs or PD-related beliefs. Results indicate that
      treatment of anxiety disorders in patients with concomitant one or more PDs is
      appropriate.

PMID- 16287392
TI  - Empirically supported treatments or type I errors? Problems with the analysis of
      data from group-administered treatments.
AB  - When treatments are administered in groups, clients interact in ways that lead to
      violations of a key assumption of most statistical analyses-the assumption of
      independence of observations. The resulting dependencies, when not properly
      accounted for, can increase Type I errors dramatically. Of the 33 studies of
      group-administered treatment on the empirically supported treatments list, none
      appropriately analyzed their data. The current authors provide corrections that
      can be applied to improper analyses. After the corrections, only 12.4% to 68.2%
      of tests that were originally reported as significant remained significant,
      depending on what assumptions were made about how large the dependencies among
      observations really are. Of the 33 studies, 6-19 studies no longer had any
      significant results after correction. The authors end by providing
      recommendations for researchers planning group-administered treatment research.

PMID- 16287394
TI  - Mediation of changes in anxiety and depression during treatment of social phobia.
AB  - To investigate the interactive process of changes in social anxiety and
      depression during treatment, the authors assessed weekly symptoms in 66 adult
      outpatients with social phobia (social anxiety disorder) who participated in
      cognitive- behavioral group therapy. Multilevel mediational analyses revealed
      that improvements in social anxiety mediated 91% of the improvements in
      depression over time. Conversely, decreases in depression only accounted for 6%
      of the decreases in social anxiety over time. Changes in social anxiety fully
      mediated changes in depression during the course of treatment. The theoretical
      and clinical implications of these findings for the relationship between anxiety
      and depression are discussed. reserved).

PMID- 16287395
TI  - Randomized trial of prolonged exposure for posttraumatic stress disorder with and
      without cognitive restructuring: outcome at academic and community clinics.
AB  - Female assault survivors (N=171) with chronic posttraumatic stress disorder
      (PTSD) were randomly assigned to prolonged exposure (PE) alone, PE plus cognitive
      restructuring (PE/CR), or wait-list (WL). Treatment, which consisted of 9-12
      sessions, was conducted at an academic treatment center or at a community clinic
      for rape survivors. Evaluations were conducted before and after therapy and at 3
      , 6-, and 12-month follow-ups. Both treatments reduced PTSD and depression in
      intent-to-treat and completer samples compared with the WL condition; social
      functioning improved in the completer sample. The addition of CR did not enhance
      treatment outcome. No site differences were found: Treatment in the hands of
      counselors with minimal cognitive- behavioral therapy (CBT) experience was as
      efficacious as that of CBT experts. Treatment gains were maintained at follow-up,
      although a minority of patients received additional treatment.

PMID- 16287396
TI  - An evaluation of cognitive processing therapy for the treatment of posttraumatic
      stress disorder related to childhood sexual abuse.
AB  - This study compared the effectiveness of cognitive processing therapy for sexual
      abuse survivors (CPT-SA) with that of the minimal attention (MA) given to a wait
      listed control group. Seventy-one women were randomly assigned to 1 of the 2
      groups. Participants were assessed at pretreatment and 3 times during
      posttreatment: immediately after treatment and at 3-month and 1-year follow-up,
      using the Clinician-Administered Posttraumatic Stress Disorder (PTSD) Scale (D.
      Blake et al., 1995), the Beck Depression Inventory (A. T. Beck, R. A. Steer, & G.
      K. Brown, 1996), the Structured Clinical Interview for the DSM-IV (R. L. Spitzer,
      J. B. W. Williams, & M. Gibbon, 1995; M. B. First et al., 1995), the Dissociative
      Experiences Scale-II (E. M. Bernstein & F. W. Putnam, 1986), and the Modified
      PTSD Symptom Scale (S. A. Falsetti, H. S. Resnick, P. A. Resick, & D. G.
      Kilpatrick, 1993). Analyses suggested that CPT-SA is more effective for reducing
      trauma-related symptoms than is MA, and the results were maintained for at least
      1 year.

PMID- 16287398
TI  - Assessing clinical significance: does it matter which method we use?
AB  - Measures of clinical significance are frequently used to evaluate client change
      during therapy. Several alternatives to the original method devised by N. S.
      Jacobson, W. C. Follette, & D. Revenstorf (1984) have been proposed, each
      purporting to increase accuracy. However, researchers have had little systematic
      guidance in choosing among alternatives. In this simulation study, the authors
      systematically explored data parameters (e.g., reliability of measurement, pre
      post effect size, and pre-post correlation) that might yield differing results
      among the most widely considered clinical significance methods. Results indicated
      that classification across methods was far more similar than different,
      especially at greater levels of reliability. As such, the existing methods of
      clinical significance appear highly comparable; future directions for clinical
      significance use and research are discussed.

PMID- 16287397
TI  - Mediated paths to over-reactive discipline: mothers' experienced emotion,
      appraisals, and physiological responses.
AB  - The present investigation was designed to evaluate whether mothers' emotion
      experience, autonomic reactivity, and negatively biased appraisals of their
      toddlers' behavior and toddlers' rates of misbehavior predicted over-reactive
      discipline in a mediated fashion. Ninety-three community mother-toddler dyads
      were observed in a laboratory interaction, after which mothers' emotion
      experience and appraisals of their toddler's behavior were measured via a video
      recall procedure. Autonomic physiology and over-reactive discipline were measured
      during the interactions. Mothers' negatively biased appraisals mediated the
      relation between emotion experience and over-reactive discipline. Heart rate
      reactivity predicted discipline independent of this mediation. Toddler
      misbehavior appeared to be an entry point into the above process. Interventions
      that more actively target physiological and experiential components of mothers'
      emotion may further reduce their over-reactive discipline.

PMID- 16287399
TI  - Evaluation of a decision-making aid for parents regarding childhood
      immunizations.
AB  - This intervention study evaluates a decision-making aid for parents considering
      childhood immunizations. Participants (women in 3rd trimester of pregnancy, n =
      100) rated likelihood of immunizing their child, anxiety, and perceptions of risk
      of the diseases and immunizations. Individuals were allocated to intervention
      group (received a decision aid) or control group (received standard care).
      Ratings were then repeated, and further ratings were obtained when the infant was
      10 weeks old. The intervention compared with the comparison condition was
      associated with significant increase in likelihood of immunizing the infant on
      time, decreased perceptions of risks of immunizations, increased perceptions of
      risk of the diseases, reduced anxiety, and increased satisfaction. This
      intervention may form a useful basis for decision aids in health care settings.

PMID- 16287401
TI  - Validation of scales measuring attitudes and norms related to mammography
      screening in women veterans.
AB  - Validation of psychosocial measures for use in mammography screening research has
      been given inadequate attention in the literature. The authors report on the
      validation of 5 measures examining 4 attitudinal constructs (i.e., pros, cons,
      outcome expectations, and cancer worries) and 1 social influence construct (i.e.,
      subjective norms) in a 22-item inventory. The study participants consisted of a
      national, randomly sampled population of women veterans (n = 2,910). After minor
      revision of scales, the authors found independent measures for 4 constructs:
      pros, cons, cancer worries, and subjective norms. The authors concluded that
      these scales have acceptable psychometric properties; support construct validity;
      and provide brief, reliable, and valid measures of attitudes toward and norms
      regarding mammography screening. These scales may be useful for intervention
      research.

PMID- 16287400
TI  - Maternal influences on daughters' restrained eating behavior.
AB  - This study examined whether mothers' preoccupation with their own weight and
      eating was linked to daughters' restrained eating behavior. Participants included
      173 non-Hispanic, White mother-daughter dyads, measured longitudinally when
      daughters were ages 5, 7, 9, and 11. Mothers who were preoccupied with their own
      weight and eating reported higher levels of restricting daughters' intake and
      encouraging daughters to lose weight over time. Mothers' encouragement of
      daughters' weight loss was linked to daughters' restrained eating behavior; this
      relationship was partially mediated by daughters' perception of maternal pressure
      to lose weight. These findings suggest that mothers' preoccupation with weight
      and eating, via attempts to influence daughters' weight and eating, may place
      daughters at risk for developing problematic eating behaviors.

PMID- 16287402
TI  - Food, mood, and attitude: reducing risk for eating disorders in college women.
AB  - Food, Mood, and Attitude (FMA) is a CD-ROM prevention program developed to
      decrease risk for eating disorders in college women. Female 1st-year students (N
      = 240) were randomly assigned to the intervention (FMA) or control group. Equal
      numbers of students at risk and of low risk for developing an eating disorder
      were assigned to each condition. Participants in the FMA condition improved on
      all measures relative to controls. Significant 3-way interactions (Time x
      Condition x Risk Status) were found on measures of internalization of
      sociocultural attitudes about thinness, shape concerns, and weight concerns,
      indicating that at-risk participants in the intervention group improved to a
      greater extent than did low-risk participants. At follow-up, significantly fewer
      women in the FMA group reported overeating and excessive exercise relative to
      controls.

PMID- 16287403
TI  - Predictors of posttraumatic stress disorder following cancer.
AB  - This study investigated the predictors of posttraumatic stress disorder (PTSD)
      following a diagnosis of cancer. Individuals who were recently diagnosed with 1st
      onset head and neck or lung malignancy (N = 82) were assessed within 1 month of
      diagnosis for acute stress disorder (ASD) and other psychological responses
      including depression; individuals were reassessed (N = 63) for PTSD 6 months
      following their cancer diagnosis. At the initial assessment ASD was diagnosed in
      28% of participants, and 22% met criteria for PTSD at 6-months follow-up.
      Peritraumatic dissociative symptoms at the time of receiving one's cancer
      diagnosis was the sole predictor of PTSD severity at 6-months follow-up. Elevated
      dissociative symptoms and greater distress at the initial assessment were the
      best predictors of PTSD caseness at 6-months follow-up. This study provides
      evidence for identifying recently diagnosed cancer patients who may benefit from
      psychological assistance in order to prevent chronic psychopathology.

PMID- 16287404
TI  - Psychosocial and health consequences of adolescent depression in Black and White
      young adult women.
AB  - Depression in adolescent girls may result in negative consequences in young
      adulthood. The Center for Epidemiologic Studies Depression Scale (CES-D) was
      administered to 1,727 Black and White girls ages 16 to 18 years who participated
      in the National Heart, Lung, and Blood Institute's Growth and Health Study. Three
      years later, women in the depressed groups were more likely to be current
      smokers, had attained a lower level of education, and reported lower self-worth
      relative to the nondepressed group. Body dissatisfaction, eating concerns, and
      loneliness were greater in the depressed groups. Relative to Black women, White
      women who were moderately depressed during adolescence reported more health care
      services utilization in young adulthood. Prevention efforts for depressed
      adolescents should be broadly focused to improve young adult outcomes.

PMID- 16287405
TI  - Terrorism and cardiovascular responses to acute stress in children.
AB  - A number of studies have considered whether background stress affects
      cardiovascular responses to acute stress tasks. The present study considers the
      effect of a potent background stressor with a clear onset, namely the terrorist
      attacks on September 11, 2001. Specifically, the authors investigated differences
      among 9.5-year-old children tested before (N = 30) and then following (N = 20)
      the 9/11 attacks. In addition, a majority of these children (N = 37) were
      retested approximately 1 year later (i.e., before and after 9/11/2002). Children
      tested directly following 9/11/2001 exhibited significantly greater stroke volume
      and cardiac output responses to acute stress tasks compared with their responses
      1 year later, and this change in reactivity differed significantly from the
      change in reactivity exhibited by children tested before 9/11/2001 and again 1
      year later. These results suggest that a potent background stressor can
      temporarily heighten some children's cardiovascular responses to subsequent acute
      stressors.

PMID- 16287406
TI  - Associations between acute lipid stress responses and fasting lipid levels 3
      years later.
AB  - The authors assessed the association between lipid responses to acute mental
      stress and fasting serum lipid levels 3 years later in 199 middle-aged men and
      women. Total cholesterol, low-density lipoprotein (LDL), and high-density
      lipoprotein (HDL) cholesterol increased following moderately stressful behavioral
      tasks. LDL cholesterol, HDL cholesterol, and total:HDL ratio measured 3 years
      later were predicted by acute stress responses independent of gender, age,
      socioeconomic position, change in body mass, smoking, alcohol consumption, or
      hormone replacement therapy baseline lipid levels. The odds of clinically
      elevated cholesterol were significantly greater in the highest compared with the
      lowest stress tertile, independent of baseline levels and covariates. Acute lipid
      stress responsivity may reflect processes that contribute to the development of
      elevated blood cholesterol concentration.

PMID- 16287407
TI  - The effects of outcome expectations and satisfaction on weight loss and
      maintenance: correlational and experimental analyses--a randomized trial.
AB  - This study examines the hypothesis that highly favorable outcome expectations
      promote weight loss and hinder weight maintenance. To investigate the effects of
      outcome expectations and satisfaction with treatment outcomes on weight loss, 349
      adults were randomly assigned to 1 of 2 weight loss programs that emphasize
      either (a) an "optimistic" message, focusing exclusively on the positive aspects
      of weight loss, or (b) a "balanced" message, giving equal time to positive and
      negative aspects of weight loss. Participants changed their weight loss
      cognitions in response to the intervention, but there was no significant
      difference between the intervention treatment groups in short-term or long-term
      (18-month) weight loss. Independent of treatment message, positive outcome
      expectations and satisfaction were both associated with weight loss.

PMID- 16287408
TI  - HIV-specific social support predicts less sexual risk behavior in gay male
      couples.
AB  - Gay male couples (N = 47) completed self-administered questionnaires at 2 time
      points (6 months apart) regarding their levels of general and HIV-specific social
      support and sexual behavior. HIV-specific social support measured partner support
      pertaining to HIV risk behavior. The sexual-risk-behavior outcome encapsulated
      monogamy, serostatus, and unprotected anal sex for each partner. The authors used
      an analytic approach that maintained the couple as the unit of analysis. General
      social support was an inconsistent predictor of HIV risk behavior. However,
      couples that reported greater levels of HIV-specific social support engaged in
      less HIV risk behavior at each time point as well as longitudinally. This study
      demonstrated the utility of measuring HIV-specific social support and its
      predictive ability related to HIV risk behavior.

PMID- 16287409
TI  - Smoking cessation: social comparison level predicts success for adult smokers.
AB  - The affiliation preferences of 151 adult heavy smokers who joined smoking
      cessation groups were assessed at the 1st group session and were then used to
      predict their smoking status 6 and 12 months later. Those who preferred to be in
      groups with other smokers who were having relatively little trouble quitting were
      more likely to be successful than were those who preferred others who were having
      more difficulty quitting. This prospective effect was mediated by psychological
      distancing from the image of the typical smoker: Preference for others who were
      doing well was associated with a decrease in perceived similarity to the typical
      smoker, which, in turn, was associated with successful cessation. Implications of
      these findings for cessation groups and social comparison theory are discussed.

PMID- 16287410
TI  - Depression in adults with type 2 diabetes: the role of adherence, body mass
      index, and self-efficacy.
AB  - Considerable evidence links depression with the development and worsening of
      diabetes, but the factors contributing to this link have not been established.
      The authors examined the role of adherence, body mass index (BMI), and self
      efficacy. Adult patients with Type 2 diabetes (N = 56) completed self-report
      measures of diet and exercise adherence, diet and exercise self-efficacy, and
      depression. BMI was obtained from medical records. Path and mediation analyses
      indicated that both adherence and BMI independently contributed to self-efficacy.
      Self-efficacy mediated both the association between adherence and depression and
      the association between BMI and depression. These findings are consistent with
      the proposal that lower self-efficacy in reaction to adherence failure and higher
      BMI contributes to depression in adults with diabetes.

PMID- 16287411
TI  - Partner unsupportive responses, avoidant coping, and distress among women with
      early stage breast cancer: patient and partner perspectives.
AB  - This 18-month longitudinal study examined the associations among partner
      unsupportive behavior, avoidant coping, and distress experienced by 219 women
      with early stage breast cancer. The role of patient and partner ratings of
      unsupportive behavior were evaluated. Results indicated that patient and partner
      ratings of unsupportive behavior were highly correlated. Growth curve modeling
      suggested that unsupportive behavior, from both patient and partner perspectives,
      predicted more avoidant coping and distress. When partner and patient perceptions
      were placed in the same model, patient perceptions mediated the association
      between partners' ratings of their unsupportive behavior and patient distress.
      Avoidance also mediated the association between unsupportive behavior and
      distress, extending prior cross-sectional findings. Results highlight the long
      term detrimental effects of partners' unsupportive behavior on the quality of
      life of women with early stage breast cancer.

PMID- 16287412
TI  - Separating multiple processes in implicit social cognition: the quad model of
      implicit task performance.
AB  - The authors argue that implicit measures of social cognition do not reflect only
      automatic processes but rather the joint contributions of multiple, qualitatively
      different processes. The quadruple process model proposed and tested in the
      present article quantitatively disentangles the influences of 4 distinct
      processes on implicit task performance: the likelihood that automatic bias is
      activated by a stimulus; that a correct response can be determined; that
      automatic bias is overcome; and that, in the absence of other information, a
      guessing bias drives responses. The stochastic and construct validity of the
      model is confirmed in 5 studies. The model is shown to provide a more nuanced and
      detailed understanding of the interplay of multiple processes in implicit task
      performance, including implicit measures of attitudes, prejudice, and
      stereotyping.

PMID- 16287413
TI  - Conceptualizing control in social cognition: how executive functioning modulates
      the expression of automatic stereotyping.
AB  - Two studies investigated the role of executive control in moderating the
      relationship between automatic stereotype activation and behavioral responses.
      Race bias in weapon identification was used to measure stereotyping, and a
      process dissociation procedure was used to measure automatic and controlled
      components of performance. In Experiment 1, the controlled component was shown to
      correlate with general attention control and race-specific motivations to control
      prejudice. Across multiple measures, automatic race bias was more likely to be
      expressed as behavioral discrimination among individuals with poor executive
      control. Experiment 2 found the same relationship between automatic and
      controlled components of behavior when predicting impressions of a Black
      individual. Executive control is discussed in the context of other control
      strategies in influential dual-process models of stereotyping.

PMID- 16287414
TI  - Biased language use in stereotype maintenance: the role of encoding and goals.
AB  - In 4 studies, the authors investigated the relative impact of biased encoding of
      information and communication goals on biased language use. A category label
      (linguistic expectancy bias, Study 1) or a group label (linguistic intergroup
      bias, Study 2) was presented either before or after a story that participants
      were asked to communicate. Biased language use only emerged when participants
      learned about the group membership of the actor or the category label before
      hearing the story. However, communication goals had an effect on language use at
      the retrieval stage, independent of encoding (Studies 3 and 4). Although
      communication goal effects seemed to overwhelm encoding effects, encoding still
      influenced language use under externally imposed time pressure (Study 3) and self
      imposed time constraints (Study 4). This research reaffirms the importance of
      both cognitive and communicative processes in stereotype maintenance and
      highlights the conditions under which they each operate.

PMID- 16287415
TI  - On the categorization of admired and disliked exemplars of admired and disliked
      racial groups.
AB  - The present work examined the influence of affective fit in the racial
      categorization process. Study 1 tested whether famous exemplars of stigmatized
      and nonstigmatized racial groups are categorized by race at differential rates,
      depending on whether they are admired or disliked. Using an inverted-face
      paradigm, Study 2 examined whether racial categorization accuracy differs for
      admired and disliked exemplars of these groups. Study 3 examined the influence of
      collective self-esteem on Whites' tendency to differentially categorize admired
      and disliked Black and White exemplars. Last, Study 4 replicated the pattern of
      results found in the previous studies for White participants, making use of
      unknown exemplars about whom participants learned either positive or negative
      information prior to categorizing them. Taken together, the results suggested
      that phenotypically irrelevant affective information regarding exemplars and
      their social group memberships influences the racial categorization process.
      Implications for prejudice and stereotyping are discussed.

PMID- 16287416
TI  - Where is the evidence for pancultural self-enhancement? A reply to Sedikides,
      Gaertner, and Toguchi (2003).
AB  - C. Sedikides, L. Gaertner, and Y. Toguchi (2003) maintained that the self
      enhancement motivation (as defined by tendencies to view oneself in overly
      positive terms) is universal. The present article challenges their claim. A
      review of the literature revealed that many studies contradict their findings
      regarding the domain-specific nature of East Asian self-enhancement. It is argued
      that Sedikides et al. did not replicate past research because they did not
      measure self-enhancement in their studies. The present article provides a
      theoretical basis for understanding cross-cultural differences in self
      enhancement and considers the question of universality by exploring 2 different
      conceptualizations of positive self-regard.

PMID- 16287418
TI  - Role rigidity: a problem of identity misclassification?
AB  - When nonstigmatized individuals enact certain role-violating behaviors, they risk
      becoming "falsely accused deviants" (H. S. Becker, 1963, p. 20). For instance,
      when heterosexual men perform stereotypically feminine behaviors, they are liable
      to get misclassified as homosexual. Findings presented here reveal that
      expectations of identity misclassification fuel nonstigmatized individuals'
      negative reactions to role violations (Studies 1-2) and that using a disclaimer-
      that is, informing their audience of their nonstigmatized identity--assuages
      people's discomfort during a role-violating behavior (Studies 3-4). Moreover,
      when not concerned about being misclassified, nonstigmatized individuals benefit
      psychologically from the enactment of a challenging role violation (Study 4).
      Discussion considers the nature of the threat that misclassified role violators
      face and compares the plight of the falsely accused deviant to that of the truly
      stigmatized individual.

PMID- 16287417
TI  - Pancultural self-enhancement reloaded: a meta-analytic reply to Heine (2005).
AB  - C. Sedikides, L. Gaertner, and Y. Toguchi (2003) reported findings favoring the
      universality of self-enhancement. S. J. Heine (2005) challenged the authors'
      research on evidential and logical grounds. In response, the authors carried out
      2 meta-analytic investigations. The results backed the C. Sedikides et al. (2003)
      theory and findings. Both Westerners and Easterners self-enhanced tactically.
      Westerners self-enhanced on attributes relevant to the cultural ideal of
      individualism, whereas Easterners self-enhanced on attributes relevant to the
      cultural ideal of collectivism (in both cases, because of the personal importance
      of the ideal). Self-enhancement motivation is universal, although its
      manifestations are strategically sensitive to cultural context. The authors
      respond to other aspects of Heine's critique by discussing why researchers should
      empirically validate the comparison dimension (individualistic vs.
      collectivistic) and defending why the better-than-average effect is a valid
      measure of self-enhancement.

PMID- 16287419
TI  - "I am us": negative stereotypes as collective threats.
AB  - Collective threat is the fear that an in-group member's behavior might reinforce
      a negative stereotype of one's group. In a field study, self-reported collective
      threat was higher in stereotyped minorities than in Whites and was linked to
      lower self-esteem in both groups. In 3 experimental studies, a potentially poor
      performance by an in-group member on a stereotype-relevant task proved
      threatening, as evidenced by lower self-esteem among minority students in 2
      experiments and women in a 3rd experiment. The latter study demonstrated the
      generality of collective threat. Collective threat also undermined academic
      performance and affected self-stereotyping, stereotype activation, and physical
      distancing from the in-group member. Results further suggest that group
      identification plays a role in whether people use an avoidance or challenge
      strategy in coping with collective threat. Implications for theories of social
      identity and stigmatization are discussed.

PMID- 16287420
TI  - Social tuning of automatic racial attitudes: the role of affiliative motivation.
AB  - Consistent with the affiliative social tuning hypothesis, this study showed that
      the desire to get along with another person shifted participants' automatic
      attitudes toward the ostensible attitudes of that person. In Experiment 1, the
      automatic racial attitudes of women but not men emulated those of an experimenter
      displaying race-egalitarian attitudes or attitudes neutral with respect to race.
      Mediational analysis revealed that the gender difference in social tuning was
      mediated by liking for the experimenter. In Experiment 2, the likability of the
      experimenter was manipulated. Individuals who interacted with a likable
      experimenter exhibited social tuning more so than did those who interacted with a
      rude experimenter. These findings suggest that affiliative motives may elicit
      malleability of automatic attitudes independent of manipulations of social group
      exemplars.

PMID- 16287421
TI  - Executive self, self-esteem, and negative affectivity: relations at the
      phenotypic and genotypic level.
AB  - Complementary approaches examined the relations among executive self, self
      esteem, and negative affectivity. A cross-sectional (N = 4,242) and a
      longitudinal (N = 158) study established that self-esteem mediated the relation
      between executive self and negative affectivity. A 3rd study (N = 878 twin pairs)
      replicated this pattern and examined genetic and environmental influences
      underlying all 3 phenotypes. Covariation among the 3 phenotypes reflected largely
      common genetic influences, although unique genetic effects explained variability
      in both executive self and negative affectivity. Executive self was influenced by
      shared environmental influences unique from those affecting self-esteem and
      negative affectivity. Non-shared environmental influences accounted for the
      majority of variance in each construct and were primarily unique to each. The
      unique genetic and non-shared environmental influences support the proposition
      that the executive self, self-esteem, and negative affectivity capture distinct
      and important differences between people.

PMID- 16287423
TI  - Simultaneous administration of the Rosenberg Self-Esteem Scale in 53 nations:
      exploring the universal and culture-specific features of global self-esteem.
AB  - The Rosenberg Self-Esteem Scale (RSES) was translated into 28 languages and
      administered to 16,998 participants across 53 nations. The RSES factor structure
      was largely invariant across nations. RSES scores correlated with neuroticism,
      extraversion, and romantic attachment styles within nearly all nations, providing
      additional support for cross-cultural equivalence of the RSES. All nations scored
      above the theoretical midpoint of the RSES, indicating generally positive self
      evaluation may be culturally universal. Individual differences in self-esteem
      were variable across cultures, with a neutral response bias prevalent in more
      collectivist cultures. Self-competence and self-liking subscales of the RSES
      varied with cultural individualism. Although positively and negatively worded
      items of the RSES were correlated within cultures and were uniformly related to
      external personality variables, differences between aggregates of positive and
      negative items were smaller in developed nations. Because negatively worded items
      were interpreted differently across nations, direct cross-cultural comparisons
      using the RSES may have limited value.

PMID- 16287422
TI  - Prejudice and stereotype maintenance processes: attention, attribution, and
      individuation.
AB  - Three experiments examined the relationship between prejudice and processing of
      stereotypic information. Higher levels of prejudice were associated with greater
      attention to and more thorough encoding of stereotype-inconsistent than
      stereotype-consistent behaviors but only when processing capacity was plentiful
      (Experiments 1 and 3). High-prejudice participants attributed consistent
      behaviors to internal factors and inconsistent behaviors to external forces
      (Experiment 2). Together, these results suggest that high-prejudice people attend
      carefully to inconsistent behaviors to explain them away but only if they have
      sufficient resources to do so. Results also showed that low-prejudice but not
      high-prejudice participants formed individuated impressions by integrating the
      implications of the target's behaviors (i.e., individuating). High levels of
      prejudice appear to be associated with biased encoding and judgment processes
      that may serve to maintain stereotypes.

PMID- 16287424
TI  - Individual differences and cross-situational consistency of dyadic social
      behavior.
AB  - A new theoretical analysis of individual differences and cross-situational
      consistency of behavior is proposed. The authors hypothesized that the social
      behavior of mice (Mus musculus) is determined by individual differences among
      animals in behavior emitted (i.e., actor effects), in behavior elicited from
      social partners (partner effects), and by unique responses of one animal to
      another (relationship effects). Each effect represents a distinct facet of
      individual differences with different psychological meaning; likewise, the cross
      situational consistency of each effect has a distinct psychological meaning.
      Individual differences in behavior emitted were observed, and these actor effects
      were consistent longitudinally. Individual differences in behavior elicited from
      social partners were observed, and these partner effects were also consistent
      longitudinally. Unique responses to specific social partners also determined
      behavior but were inconsistent longitudinally. The theoretical importance of
      reconceptualizing the concepts of individual differences and cross-situational
      consistency in behavior is discussed. ((c) 2005 APA, all rights reserved).

PMID- 16287425
TI  - Haematopoietic stem cells and repair of the ischaemic heart.
AB  - HSCs (haematopoietic stem cells) are multipotent stem cells that give rise to all
      cells of the blood cell lineage. In recent years, it has been proposed that bone
      marrow serves as a reservoir for cardiomyogenic precursors and that, following
      cardiac injury, these stem cells circulate to the site of injury where they
      contribute to myocardial repair and regeneration. This concept of stem cell
      plasticity has been controversial and, in fact, several key studies on the
      cardiomyogenic potential of HSCs have not been reproducible in the hands of
      independent investigators. Despite this controversy, the clinical community has
      pushed forward with clinical trials of bone marrow transplantation for the
      treatment of ischaemic heart disease. The following review summarizes the
      mechanistic underpinnings of bone marrow transplantation into ischaemic
      myocardium, focusing on the basic science that forms the foundation of this
      field, and highlights the controversies and new avenues for research that have
      emerged. It also describes the current state of the art in clinical trials of
      bone marrow transplantation for heart failure.

PMID- 16287427
TI  - What role do adrenoreceptor polymorphisms play in modifying cardiovascular
      responses in obstructive sleep apnoea?
AB  - OSA (obstructive sleep apnoea) is a common condition that is strongly associated
      with cardiovascular disease. It is remains unclear what role OSA plays in
      determining cardiovascular risk. The immediate physiological changes that occur
      during upper airway obstruction are potential contributors to cardiovascular risk
      in OSA. These changes include increased sympathetic activity, which is responsive
      to treatment of OSA with CPAP (continuous positive airway pressure). In this
      issue of Clinical Science, the possible role of a common polymorphism in the
      beta1-adrenoreceptor [R389G (Arg389Gly)] has been investigated by Borgel and co
      workers. Measurements of heart rate and blood pressure in untreated OSA patients
      were not related to the R389G polymorphism. There were changes in heart rate and
      diastolic blood pressure with CPAP treatment that were related to this
      polymorphism. Reduction in heart rate with CPAP treatment was associated with the
      R389R genotype. By contrast, a reduction in diastolic blood pressure was
      associated with the Gly389 carriers. These findings are intriguing, but difficult
      to fully explain. Further study is needed to determine if there is an important
      role of the R389G polymorphism in modifying cardiovascular responses among OSA
      patients.

PMID- 16287426
TI  - Interactive domains between pore loops of the yeast K+ channel TOK1 associate
      with extracellular K+ sensitivity.
AB  - Gating of the outward-rectifying K+ channel TOK1 of Saccharomyces cerevisiae is
      controlled by membrane voltage and extracellular K+ concentration. Previous
      studies identified two kinetically distinct effects of K+, and site-mutagenic
      analysis associated these K+-dependencies with domains of the extracellular
      turrets of the channel protein. We have mapped the TOK1 pore domains to extant K+
      channel crystal structures to target additional residues contributing to TOK1
      gating. Leu270, located in the first pore domain of TOK1, was found to be
      critical for gating and its K+ sensitivity. Analysis of amino acid substitutions
      indicated that spatial position of the polypeptide backbone is a primary factor
      determining gating sensitivity to K+. The strongest effects, with L270Y, L270F
      and L270W, led to more than a 30-fold decrease in apparent K+ affinity and an
      inversion in the apparent K+-dependence of voltage-dependent gating compared with
      the wild-type current. A partial rescue of wild-type gating was obtained on
      substitution in the second pore domain with the double mutant L270D/A428Y. These,
      and additional results, demarcate extracellular domains that are associated with
      the K+-sensitivity of TOK1 and they offer primary evidence for a synergy in
      gating between the two pore domains of TOK1, demonstrating an unexpected degree
      of long-distance interaction across the mouth of the K+ channel.

PMID- 16287428
TI  - Shared decision-making and informed choice for the early detection of prostate
      cancer in primary care.

PMID- 16287429
TI  - Could urological questionnaires completely replace physiological testing?

PMID- 16287430
TI  - The protective effects of green tea in prostate cancer.

PMID- 16287431
TI  - Hypertension and the role of the urologist.

PMID- 16287432
TI  - The future of British surgery.

PMID- 16287433
TI  - When thinking of initiating medical therapy for lower urinary tract symptoms, ask
      about cataracts.

PMID- 16287434
TI  - A tumour stem cell hypothesis for the origins of prostate cancer.
AB  - Cancer stem cells undoubtedly exist in many tumour types, including the prostate.
      This hypothesis can explain both the heterogeneity of prostate tumours and their
      variable responses to several conventional therapies. In the longer term,
      therapies directed against tumour stem cells should offer a real possibility of
      long-term cure, rather than current palliative therapy. Identifying specific
      tumour stem-cell markers will enhance this process, but the scarcity of these
      cells within the mass of more differentiated amplifying progeny that comprise
      >99.9% of most cancers makes this a severe technical challenge. In addition, many
      tumour stem-cell markers are probably shared with normal stem cells, both in
      prostate and in stem cells from other tissues, but tumour-specific patterns of
      gene expression, probably designed to allow the tumour stem cell to survive
      outside its protective 'niche' in normal tissues, will be the best initial
      targets for new therapeutic agents.

PMID- 16287435
TI  - Comparison of cryoablation, radiofrequency ablation and high-intensity focused
      ultrasound for treating small renal tumours.

PMID- 16287436
TI  - Emerging minimally invasive techniques for treating localized prostate cancer.

PMID- 16287437
TI  - Current status of dynamic lymphoscintigraphy and sentinel lymph-node biopsy in
      urological malignancies.

PMID- 16287438
TI  - Selective blockade of androgenic steroid synthesis by novel lyase inhibitors as a
      therapeutic strategy for treating metastatic prostate cancer.

PMID- 16287439
TI  - Factors contributing to the racial differences in prostate cancer mortality.
AB  - OBJECTIVE: To analyse, in a retrospective cohort study, differences in rates of
      surgical treatment for prostate cancer between African-Americans and White
      Americans, and to evaluate the extent to which these differences are associated
      with disparities in survival rates between these groups. PATIENTS AND METHODS:
      Clinical, pathological, and demographic data from 4279 men diagnosed with
      clinically localized prostate cancer between 1980 and 1997 were used. The
      variables assessed included age, disease stage, tumour grade, comorbidities,
      treatment method, and socio-economic status (SES). Kaplan-Meier survival curves
      were generated and compared using log-rank tests. The Cox proportional hazards
      method was used for analyses involving adjustments for potential confounding
      factors. RESULTS: The surgical treatment rate was 17% for African-American and
      28% for White patients (P < 0.001). In those patients treated conservatively or
      by radiation therapy, both crude and cancer-specific survival rates were lower
      for African-Americans than for Whites (P < 0.001). However, for patients
      undergoing surgery, differences in survival between African-Americans and Whites
      were not statistically significant. According to our models, SES explained 50%
      and surgical treatment rates approximately 34% of the differences in survival
      between African-Americans and Whites. CONCLUSIONS: This analysis suggests that
      the lower prostate cancer survival rates for the African-Americans in the present
      population can be largely explained by differences in SES and lower surgical
      treatment rates. Efforts to increase awareness of treatment options among African
      American patients may be a way of improving survival in this group.

PMID- 16287440
TI  - Visual estimation of tumour extent is not an independent predictor of prostate
      specific antigen recurrence.
AB  - OBJECTIVE: To analyse tumour extent as a predictor of cancer progression after
      radical prostatectomy (RP), using a multivariate Cox regression model, as several
      variables (e.g. Gleason grade and tumour stage) are well-established prognostic
      factors in prostate cancer but it is uncertain if the visual estimation of tumour
      extent (percentage of carcinoma) is an independent predictor for prostate cancer
      recurrence. PATIENTS AND METHODS: Tumour extent was estimated in the RP specimens
      from 504 men with clinically localized prostate cancer; clinical follow-up data
      were available for 459 men. The mean (range) follow-up was 44.3 (1.5-144) months.
      Cancer progression was defined by the development of biochemical recurrence,
      local recurrence, or distant metastasis. Multivariate analysis was used to assess
      tumour extent as a predictor of cancer progression. RESULTS: Of the 459 patients,
      157 had cancer progression; the mean tumour extent was 36% and 24% in those with
      and without cancer progression, respectively (P < 0.001). Univariate analysis
      showed a significant association between the visual estimation of tumour extent
      and tumour stage, Gleason grade, surgical margins, extraprostatic extension,
      seminal vesicle invasion, lymph node metastasis, and preoperative serum prostate
      specific antigen level (all P < 0.001). However, in a multivariate Cox regression
      model controlling for pathological stage, Gleason score, and surgical margin
      status, the visual estimation of tumour extent was no longer a significant
      predictor of cancer progression (P = 0.84). CONCLUSION: The visual estimation of
      tumour extent was associated with various established prognostic factors for
      prostate cancer, and with cancer progression in a univariate analysis, but it was
      not a significant predictor of cancer progression in the multivariate analysis
      controlling for pathological stage, Gleason score, and surgical margin status.

PMID- 16287441
TI  - The percentage of positive biopsy cores as a predictor of disease recurrence in
      patients with prostate cancer treated with radical prostatectomy.
AB  - OBJECTIVE: To analyse the prognostic value of the percentage of positive biopsy
      cores (PPBC) in determining the pathological features and biochemical outcome of
      patients with prostate cancer treated by radical prostatectomy, as published data
      evaluating the prognostic value of PPBC in such patients have limitations.
      PATIENTS AND METHODS: A group of 534 patients with clinically localized prostate
      cancer was selected. The PPBC was defined as the number of positive biopsy
      cores/total number of biopsy cores x 100, and grouped into categories of <25%,
      25.1-50%, 50.1-75% and 75.1-100%. Patients were divided in low-, intermediate-
      and high-risk groups according to the usual variables. RESULTS: The mean follow
      up was 60.5 months. PPBC was associated with the preoperative serum prostate
      specific antigen (PSA) level, biopsy Gleason score and clinical stage. On
      multivariate analysis, PPBC was a significant predictor of extraprostatic disease
      and seminal vesicle involvement. Of patients in the four PPBC categories, 16%,
      27%, 33% and 60%, respectively, had biochemical recurrence (P < 0.001), and on
      Cox regression analysis, PPBC was an independent predictor of disease recurrence.
      After segregating patients into risk groups the PPBC further stratified patients
      using thresholds of 75% (P = 0.006), 25% (P = 0.026) and 50% (P = 0.011) for low
      , intermediate- and high-risk groups, respectively. CONCLUSIONS: We confirmed,
      with a longer follow-up, the clinical utility of the PPBC in determining the
      pathological features and biochemical outcome of patients with prostate cancer
      treated with radical prostatectomy, and established thresholds for use in
      patients in the three risk groups.

PMID- 16287442
TI  - Perianal and intrarectal anaesthesia for transrectal biopsy of the prostate: a
      prospective randomized study comparing lidocaine-prilocaine cream and placebo.
AB  - OBJECTIVES: To assess the effectiveness of perianal and intrarectal lidocaine
      prilocaine cream for prostate biopsy. PATIENTS AND METHODS: In a prospective,
      randomized, double-blind, placebo-controlled study, 200 consecutive patients were
      randomized to receive 5 mL lidocaine-prilocaine cream or 5 mL placebo peri-anally
      and transrectally before transrectal ultrasonography (TRUS)-guided prostate
      needle biopsy (mean number of cores, 12). The men were asked to grade the pain
      when the TRUS probe was inserted and during the biopsy procedure using a 10-point
      linear visual analogue pain scale. RESULTS: At probe insertion, men in the
      anaesthetic group reported a significantly lower mean pain level than men in the
      placebo group (0.3 vs 1.6, P < 0.001). Men who had anaesthetic also reported less
      pain during biopsy punctures (1.8 vs 3.2, P < 0.001). Stratifying results by age,
      younger men (< 67 years) benefited more from anaesthesia during probe insertion
      (0.9 vs 1.7; P = 0.04) and biopsy (1.8 vs 4.0, P < 0.001) than older men (1.0 vs
      1.1, P = 0.7 and 1.9 vs 2.4, P = 0.3, respectively). There were only minor
      complications, and these were not significantly different between the groups.
      CONCLUSION: Topical anaesthesia with prilocaine-lidocaine cream significantly
      reduced pain at transrectal probe insertion and during the biopsy procedure.

PMID- 16287443
TI  - Open surgical management of renal cell carcinoma in the era of minimally invasive
      kidney surgery.

PMID- 16287444
TI  - Renal oncocytoma: a clinicopathological analysis of 45 consecutive cases.
AB  - OBJECTIVE: To evaluate the clinical behaviour and pathology of renal oncocytoma
      in a well-defined population over a 30-year period. PATIENTS AND METHODS: In a
      retrospective population-based study we assessed relevant clinical and
      pathological factors in 45 patients (31 men and 14 women) diagnosed with renal
      oncocytoma in Iceland between 1971 and 2000. Clinical presentation, pathology,
      survival and causes of death were evaluated. RESULTS: The age-standardized
      incidence was 0.3 per 100,000 per year for both men and women, the incidence of
      oncocytomas being 5.5% of renal cell carcinomas (RCCs) diagnosed during the same
      period in Iceland. Fourteen patients were diagnosed at autopsy for an unrelated
      disease. Of 31 living patients (mean age 70.5 years), seven were diagnosed
      incidentally (23%), and the others had presented with haematuria (32%), abdominal
      pain (29%), and weight loss (10%). All the patients had a radical nephrectomy,
      except for one with bilateral oncocytoma who had a partial nephrectomy. The mean
      (range) tumour size was 5.7 (0.9-12) cm. Eighteen patients (58%) were diagnosed
      at Tumour-Node-Metastasis stage I, 10 at stage II (32%) and three at stage III
      (10%), all of those at stage III having renal capsular penetration or tumour
      invasion into perirenal fat tissue (T3aN0M0). No patients were diagnosed with
      lymph node or distant metastasis. Two cases of coexisting RCC were detected.
      After a median follow-up of 8.3 years there were no recurrences or deaths from
      oncocytoma (100% disease-specific survival). The overall 5-year survival was 63%,
      with most patients dying from cardiovascular diseases or nonrenal cancers.
      CONCLUSIONS: In most cases renal oncocytoma behaves like a benign tumour; the
      long-term prognosis is excellent. Thus, in the present patients, radical
      nephrectomy could be regarded as an over-treatment and nephron-sparing surgery as
      more appropriate, especially in patients with small tumours. However, both
      coexisting RCC and perirenal fat invasion, a hallmark of malignant behaviour,
      might indicate that more radical surgery is warranted in some of these patients.

PMID- 16287446
TI  - Is adjuvant chemotherapy for bladder cancer safer in patients with an ileal
      conduit than a neobladder?
AB  - OBJECTIVE: To assess the safety of adjuvant chemotherapy in patients with
      neobladder reconstruction in comparison to ileal conduit, as radical cystectomy
      and urinary diversion is an effective curative surgical treatment for muscle
      invasive and high-risk superficial bladder cancer, and adjuvant chemotherapy is
      usually considered for patients with clinical stage > T2 and nodal metastasis.
      PATIENTS AND METHODS: We analysed retrospectively patients who had had a radical
      cystectomy and urinary diversion between 1992 and 2004. Patients with high-risk
      disease who had adjuvant chemotherapy were identified and stratified based on the
      type of urinary diversion (ileal conduit or neobladder). The chemotherapy
      regimen, complications from the adjuvant chemotherapy and other relevant data
      were analysed. RESULTS: Overall, 343 patients had radical cystectomy, 40 had
      adjuvant chemotherapy; 25 had an ileal conduit and 15 had a neobladder. Patient
      characteristics including age, stage and follow-up were similar. In all, 55% of
      patients had grade 1 toxicity, 23% grade 2, 18% grade 3, and 13% grade 4. No
      patients had serious organ toxicity and none died. There were no significant
      differences in the toxicity among the two groups. CONCLUSIONS: Adjuvant
      chemotherapy appears to be safe in patients with a neobladder and equally safe in
      patients with an ileal conduit. Hence neobladder reconstruction should not be
      denied to patients with bladder cancer who are at high risk of recurrence and who
      might require adjuvant chemotherapy.

PMID- 16287447
TI  - Intravesical bacillus Calmette-Guerin therapy: experience with a reduced dwell
      time in patients with pronounced side-effects.
AB  - OBJECTIVE: To report the side-effects after a reduction in the dwell-time in
      patients who had pronounced symptoms after intravesical bacillus Calmette-Guerin
      (BCG) treatment, as side-effects such as fever, haematuria, and frequency are
      common and sometimes severe after BCG treatment in patients with bladder cancer.
      PATIENTS AND METHODS: The dwell-time was reduced to < or = 30 min in 51 patients
      who had pronounced side-effects after the preceding BCG instillation. All
      patients self-reported side-effects after each instillation in a questionnaire.
      RESULTS: After reducing the BCG dwell-time, fever, chills, dysuria and the
      overall time-to-recovery were significantly reduced but frequency and haematuria
      were not influenced. Patients with carcinoma in situ had significantly less
      dysuria than patients with papillary tumours. There was no difference in the
      treatment results between patients who had a normal dwell-time and a reduced
      dwell-time, determined at the first and second follow-up cystoscopy. CONCLUSION:
      Reducing the BCG dwell-time to < or = 30 min could be an alternative to a dose
      reduction in patients who experience pronounced side-effects after BCG
      instillations. The long-term outcome after reducing dwell-time and after dose
      reduction has not been studied and warrants further investigation.

PMID- 16287445
TI  - Fluorescence in situ hybridization for detecting transitional cell carcinoma:
      implications for clinical practice.
AB  - OBJECTIVE: To determine the diagnostic sensitivity of genetic studies using
      fluorescence in situ hybridization (FISH) for detecting both new and recurrent
      cases of transitional cell carcinoma (TCC) in a routine clinical practice
      setting, as bladder cancer has a significant risk of recurrence and progression
      to invasive disease and thus sensitive surveillance testing is very important.
      PATIENTS AND METHODS: FISH was performed using the UroVysion kit (Vysis Inc.,
      Downers Grove, IL, USA) Consecutive patients were assessed using FISH, both to
      evaluate those with a history of TCC or with suspicious symptoms, and the FISH
      results were compared with concurrent biopsy and cytological assessments.
      RESULTS: In all, 521 consecutive FISH tests from 300 patients were evaluated; 47%
      had a history of bladder cancer and 53% had suspicious symptoms. Of the 521 FISH
      tests, 24% were positive; concurrent cytology was available for 84% of the FISH
      tests, with a concordance rate of 78% (6% were positive for both and 72% were
      negative by both tests). For the discordant cases, FISH was positive and cytology
      negative in 21% of cases, and cytology was positive with a negative FISH for 1%.
      In all, 99 FISH tests had concurrent biopsy data. Of the 44 cases histologically
      positive for TCC, 32 were FISH-positive, resulting in an overall sensitivity (95%
      confidence interval) of 73 (60-88)%. FISH detected 95% of cases with high-grade
      carcinoma, while only seven of these 17 were positive by concurrent cytological
      assessment. FISH detected 56% and cytology detected 32% of low-grade lesions.
      FISH detected all nine new cases with positive histology. Overall, the
      specificity of FISH was 65 (53-78)%. Of 112 patients with previous TCC, 28 had a
      recurrence; 22 of these had positive FISH results. CONCLUSION: FISH analysis has
      a high sensitivity for detecting new cases of TCC, as well as recurrences. From
      the present data FISH is considerably more sensitive and only slightly less
      specific than cytology in diagnosing TCC. Therefore, we recommend FISH as a
      useful initial diagnostic tool in patients suspected of both new and recurrent
      TCC.

PMID- 16287448
TI  - The natural history of lower urinary tract dysfunction in men: minimum 10-year
      urodynamic follow-up of untreated detrusor underactivity.
AB  - OBJECTIVES: To assess the long-term symptomatic and urodynamic outcomes of men
      with untreated detrusor underactivity (DUA) as there has been little long-term
      follow-up information on men with DUA, a cause of lower urinary tract symptoms
      (LUTS) in a significant minority of men. PATIENTS AND METHODS: Neurologically
      intact men aged > 18 years who were investigated in our department between 1972
      and 1986, diagnosed with DUA, and who initially opted for no specific treatment
      were invited for a repeat symptomatic and urodynamic evaluation. Identical
      methods of assessment were used, allowing results to be compared directly.
      RESULTS: In all, 224 men were initially diagnosed with DUA; 87 (39%) of these
      died. Of the 69 men who initially opted for a conservative approach and attended
      for repeat assessment, 58 (84%) remained untreated, with a mean follow-up of 13.6
      years. There were no significant changes in symptoms over the follow-up. The only
      significant urodynamic finding was an increase in the proportion of patients with
      detrusor overactivity, but with no apparent worsening of chronic retention. Of
      the 11 men in who failed the conservative approach, eight proceeded to surgery
      for LUTS, and three for acute urinary retention. CONCLUSIONS: These results
      provide important information on the natural history of DUA. In men with DUA
      presenting with LUTS there are few symptomatic and urodynamic changes with time.

PMID- 16287449
TI  - The natural history of lower urinary tract dysfunction in men: minimum 10-year
      urodynamic follow-up of untreated bladder outlet obstruction.
AB  - OBJECTIVES: To assess the long-term outcomes of untreated bladder outlet
      obstruction (BOO), assuming that, if there is little or no deterioration, a
      conservative approach to management is justified, as there is little information
      on the natural history of untreated BOO and lower urinary tract symptoms (LUTS)
      in men, and studies to date suggest that neither BOO nor LUTS inevitably progress
      to a stage at which prostatectomy is required. PATIENTS AND METHODS: Men aged >45
      years who were investigated in our department between 1972 and 1986, diagnosed
      with BOO, and who initially opted for no specific treatment were invited for
      repeat symptomatic and urodynamic evaluation. Identical methods of assessment
      were used, allowing results to be compared directly. RESULTS: In all, 1068 men
      were initially diagnosed with BOO; 428 (40%) of these died. Of the 170 men who
      initially opted for a conservative approach and attended for repeat assessment,
      141 (83%) remained untreated, with a mean follow-up of 13.9 years. The only
      significant urodynamic changes were a reduction in detrusor contractility and an
      increased prevalence of detrusor overactivity. Most patients reported no change
      in their symptoms but a significant minority experienced a gradual deterioration.
      Of the 29 men in whom the conservative approach failed, 22 proceeded to surgery
      for LUTS, and seven for acute urinary retention. CONCLUSIONS: Patients with
      untreated BOO do not significantly deteriorate urodynamically in the long term,
      with only a minority deteriorating symptomatically. These findings justify a
      conservative approach to men with LUTS associated with BOO.

PMID- 16287450
TI  - Does information provided to men before a urodynamic study affect their
      expectation of pain?
AB  - OBJECTIVE: To evaluate the effect of a routine explanation provided to men on
      their expectation of pain associated with a urodynamic study (UDS). PATIENTS AND
      METHODS: The purpose of UDS is to reproduce patient's symptoms during the urine
      storage and voiding phases, and thus understand the causes of the patient's
      symptoms. UDS may cause discomfort and pain, mainly from the urethral
      instrumentation; the fear of pain related to UDS may affect the patients'
      behaviour and the information provided by them, and thus may alter the
      conclusions drawn from the study. Routinely as with any other invasive
      procedures, patients are provided with an explanation about the UDS. Sixty-three
      men referred for UDS in an outpatient clinic, who had not had previous UDS, were
      included (mean age 56.4 years, range 25-89). Of these patients, 15 had had
      previous instrumentation of the urethra (urethral catheterization, cystoscopy),
      and 14 had had a prostatectomy. One urologist provided a detailed explanation of
      the different stages of the UDS. Use of an anaesthetic gel, and instrumentation
      of the urethra and anus by an experienced urologist, were emphasized. Pain was
      assessed using a visual analogue pain scale three times, to provide an expected
      pain score (EPS) on entering the examination room, after the explanation, and the
      actual pain felt during the UDS. RESULTS: The mean EPS before the explanation was
      4.2, significantly higher (5.17) after the explanation (P = 0.02) and the actual
      pain scored during the UDS was 3.76, lower than both the previous EPS. In
      patients who had had previous instrumentation of the urethra, the EPS after the
      explanation was significantly higher, at 6.06 (P < 0.05). Pain scores were not
      significantly different in patients after prostatectomy. CONCLUSIONS: The routine
      guidance provided to male patients undergoing UDS enhances their expectations of
      pain, especially in those who have had previous instrumentation of the urethra.
      As the fear of pain may alter the information provided by the patient, different
      strategies of providing patients with information about UDS should be devised.

PMID- 16287451
TI  - Clinical observations of the effect of antidiuretic hormone on nocturia in
      elderly men.
AB  - OBJECTIVE: To evaluate the effect of desmopressin on nocturia, based on patients'
      subjective scoring of nocturia, as desmopressin is widely used to treat nocturnal
      enuresis and nocturnal polyuria. PATIENTS AND METHODS: We investigated a specific
      subgroup of 28 men with benign prostate obstruction and nocturia who were treated
      with desmopressin. Patients with nocturnal polyuria were excluded. All the
      patients were refractory to treatment with antimuscarinics or anticholinergics,
      e.g. oxybutynin, tolterodine, and propantheline bromide. We assessed the effect
      of desmopressin using a quantitative nocturia score and analysed its synergistic
      effect with alpha-blockers. RESULTS: The mean frequency of nocturia was 6.1
      before desmopressin and most (86%) patients had an improvement in nocturia within
      1-12 weeks of treatment with desmopressin. There was a 43% reduction in nocturia
      after using desmopressin (P < 0.001). The correlation coefficient between the
      number of nocturnal voids and the reduction in nocturia after treatment with
      desmopressin was 0.756, indicating that the more severe the nocturia, the more
      effective was desmopressin. CONCLUSIONS: Desmopressin is effective for refractory
      nocturia in elderly men with no nocturnal polyuria, and has limited side-effects.

PMID- 16287452
TI  - An epidemiological survey of overactive bladder symptoms in Japan.
AB  - OBJECTIVE: To report an epidemiological survey of lower urinary tract symptoms
      (LUTS) to determine the prevalence of overactive bladder (OAB) symptoms (defined
      as a symptom complex of daily urinary frequency of eight or more times and
      urgency once or more per week) in Japan. SUBJECTS AND METHODS: A self
      administered questionnaire was mailed to 10,096 Japanese men and women aged > or
      = 40 years selected by a two-stage randomized process. Survey questions,
      developed by members of the Japan Neurogenic Bladder Society Committee, covered
      four areas: demographic characteristics, LUTS, health-related quality of life
      (HRQoL), and hospital attendance. RESULTS: The responses from 4570 respondents
      (mean age 61 years) were analysed. The estimated prevalence of OAB was 12.4% (men
      14%, women 11%). Prevalence rates for OAB with and without urgency incontinence
      (one or more episode/week) were 6.4% and 6.0%, respectively. Prevalence rates
      increased with age; 5% of respondents aged 40-49 and 37% of those aged > or = 80
      years had OAB. HRQoL was compromised in 53% of respondents with OAB symptoms,
      specifically emotions (42%), sleep/vitality (37%), physical limitation (34%),
      role limitation (29%), and social limitation (22%). Among those whose HRQoL was
      affected, 23% (men 36%, women 8%) had visited a medical institution because of
      their urinary problems. CONCLUSION: The results from this survey indicate that
      the prevalence of OAB was high and increased with age, but the rate of hospital
      attendance was low. Public awareness of OAB should be increased so that there can
      be optimum management of this condition.

PMID- 16287453
TI  - Randomized, placebo-controlled trial showing that finasteride reduces prostatic
      vascularity rapidly within 2 weeks.
AB  - OBJECTIVE: To measure expression of vascular endothelial growth factor (VEGF) and
      microvessel density (MVD) in the prostates of men after transurethral resection
      of the prostate (TURP) following 2 weeks of treatment with finasteride. PATIENTS
      AND METHODS: Sixty-four men scheduled to undergo TURP were randomized to receive
      5 mg of finasteride or placebo daily for 2 weeks before surgery. Sections of
      prostatic urothelium were stained for VEGF expression and for CD31 to assess MVD.
      Ten consecutive, non-overlapping high-power fields were analysed in a blinded
      fashion. RESULTS: In all, 31 men received finasteride and 33 placebo; the groups
      were similar in patient age, resected prostate weight, preoperative
      catheterization, prostate-specific antigen level, aspirin use, spinal anaesthesia
      and postoperative diagnosis of prostate cancer. The mean (95% confidence
      interval) MVD was significantly lower in the finasteride group (60, 55-65) than
      in the placebo group (71, 64-78; P < 0.01). Similarly, the mean expression of
      VEGF was significantly lower in the finasteride group (47, 43-52 vs 61, 54-67; P
      < 0.001) CONCLUSION: Finasteride inhibits angiogenic growth factors leading to
      reduced vascularity, and this is the basis of its action in reducing haematuria
      of prostatic origin. The present study shows that finasteride influences the
      prostatic microvasculature after only 2 weeks exposure.

PMID- 16287455
TI  - Neurophysiology of the ejaculatory process: developing perspectives.

PMID- 16287454
TI  - An open-label, multicentre, randomized, crossover study comparing sildenafil
      citrate and tadalafil for treating erectile dysfunction in men naive to
      phosphodiesterase 5 inhibitor therapy.
AB  - OBJECTIVES: To compare treatment preference, efficacy, and tolerability of
      sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction
      (ED) in men naive to phosphodiesterase 5 (PDE5) inhibitor therapy. PATIENTS AND
      METHODS: This was an open-label, crossover study of sildenafil and tadalafil
      (taken as needed). After a 4-week baseline assessment, 367 men with ED (mean age
      54 years) were randomized to receive sildenafil for 12 weeks followed by
      tadalafil for 12 weeks or vice versa (8-week dose optimization and 4-week
      assessment phases). During dose optimization, patients started taking 25- or 50
      mg sildenafil or 10-mg tadalafil and could titrate to find their optimum dose (25
      , 50- or 100-mg sildenafil; 10- or 20-mg tadalafil). After completing both 12
      week periods, patients chose which treatment to continue during an 8-week
      extension. Efficacy was measured with the International Index of Erectile
      Function (IIEF) and Sexual Encounter Profile (SEP) diary. RESULTS: Of the 291 men
      who completed both treatments, 85 (29%) chose sildenafil and 206 (71%) chose
      tadalafil (P < 0.001) for the 8-week extension. The IIEF erectile function domain
      scores were 14.2 at baseline, 23.9 at endpoint on sildenafil, and 24.3 at
      endpoint on tadalafil (P = 0.08, sildenafil vs tadalafil). The mean per patient
      percentage success scores for SEP2 (penetration) were: baseline (46%), sildenafil
      (post-baseline 82%) and tadalafil (post-baseline 85%; P = 0.06, sildenafil vs
      tadalafil), and for SEP3 (successful intercourse) were: baseline (19%),
      sildenafil (post-baseline 72%), and tadalafil (post-baseline 77%; P = 0.003,
      sildenafil vs tadalafil). The only treatment-emergent adverse events that were
      reported by >5% of men were headache and flushing. CONCLUSIONS: In men with ED
      who were naive to PDE5 inhibitor therapy, sildenafil and tadalafil were both
      effective and well tolerated. After treatment with sildenafil and tadalafil, 29%
      of men chose sildenafil and 71% chose tadalafil for ED therapy during an 8-week
      extension.

PMID- 16287456
TI  - Lower urinary tract symptoms and male sexual dysfunction in Asia: a survey of
      ageing men from five Asian countries.
AB  - OBJECTIVE: To determine, using the Asian Survey of Aging Males (ASAM), the
      prevalence of lower urinary tract symptoms (LUTS) and sexual disorders in Asian
      men aged 50-80 years, and to investigate the relationship between LUTS and sexual
      dysfunction, as community-based studies have shown a relationship between LUTS
      and sexual dysfunction. SUBJECTS AND METHODS: The ASAM survey was conducted in
      selected cities in five Asian countries, using a combination of face-to-face and
      mail-survey methods. The survey evaluated demographics, urinary symptoms (using
      the International Prostate Symptom Score, IPSS, and bother score), functional
      problems (using the Danish Prostatic Symptoms Score, DAN-PSS-Sex, and
      International Index of Erectile Function, IIEF) and comorbidity factors. In all,
      1155 men aged 50-80 years completed the survey. RESULTS: The prevalence of LUTS
      varied among the countries, ranging from 14% in Singapore to 59% in the
      Philippines. Moderate to severe LUTS were reported by 36% of men aged 50-59
      years, 50% aged 60-69 years and 60% aged 70-79 years. About three-quarters of all
      respondents (72%) aged 50-80 years were sexually active. Erectile dysfunction was
      reported by 63% of men in the study, of whom 57% were bothered by their symptoms.
      Ejaculation disorders were present in 68% of respondents (52% reported
      bothersomeness) and pain on ejaculation was experienced by 19% of the men in the
      study (88% reported bothersomeness). Sexual disorders increased with age and
      increasing severity of their LUTS. Erectile and ejaculation problems were more
      common in subjects with diabetes or hypertension; these two groups showed the
      same relationship between LUTS severity and sexual disorders. CONCLUSION: These
      results confirmed that sexual activity is common in Asian men aged 50-80 years,
      even at an advanced age. They also confirmed the correlation between LUTS and
      sexual dysfunction.

PMID- 16287457
TI  - Smoking and other lifestyle factors in relation to erectile dysfunction.
AB  - OBJECTIVE: To assess the association between erectile dysfunction (ED) and
      various lifestyle and medical factors, including smoking and cardiovascular
      disease (CVD) medications, among men attending urology clinics in Kingston,
      Canada. SUBJECTS AND METHODS: We conducted a case-control study of men aged 50-80
      years in Kingston, Ontario who agreed to participate at visits to urology clinics
      during 1997-99. We compared 101 men with clinically diagnosed ED and 234 controls
      with various benign urological conditions. All men completed a questionnaire on
      lifestyle and medical factors. RESULTS: Men with ED were twice as likely to be
      former smokers (odds ratio 2.2, 95% confidence interval, 1.2-3.9), and cumulative
      smoking in pack-years suggests a dose-response pattern with the risk of ED.
      Having diabetes was associated with double the risk of ED, and increased alcohol
      intake appeared to increase the risk. CONCLUSION: There was a greater risk of ED
      among former smokers, and the suggestion of a dose-response relationship with
      cumulative smoking.

PMID- 16287458
TI  - Development and evaluation of a prostate sexual rehabilitation clinic: a pilot
      project.
AB  - OBJECTIVE: To evaluate a sexual rehabilitation service for men with prostate
      cancer and to use these results to inform the development of future care.
      PATIENTS AND METHODS: The study participants included 155 men with prostate
      cancer referred to a sexual rehabilitation clinic by their urologists or
      radiation oncologists, of whom the partners of 58 were in attendance.
      Questionnaires to measure sexual function and positive feelings towards the
      partner were completed before the clinic visit; and for satisfaction with the
      clinic service immediately after the appointment; and for sexual function,
      positive feelings towards the partner, and satisfaction with treatments at 4
      months afterward. RESULTS: Ninety patients completed the 4-month evaluation, of
      whom 35 were couples. Enhancement of erection and understanding sexual changes
      related to treatment were the two main concerns of patients. Phosphodiesterase-5
      inhibitors and intracavernosal injections were the treatments of choice. Compared
      with partners, patients had significantly greater positive feelings towards their
      partners at both measurement times and were more satisfied with their prescribed
      treatment. The total scores on sexual function were significantly higher at 4
      months. CONCLUSIONS: These results support the need to include partners as a
      necessary part of these men's sexual rehabilitation. A structured follow-up is
      necessary to monitor the success of treatment and to document the quality of
      erection.

PMID- 16287459
TI  - Concomitant management of renal calculi and pelvi-ureteric junction obstruction
      with robotic laparoscopic surgery.
AB  - OBJECTIVE: To present technical recommendations for robotic-assisted laparoscopic
      pyeloplasty (RALP) and stone extraction, as patients with kidney stones proximal
      to a pelvi-ureteric junction obstruction (PUJO) present a technical challenge,
      and have traditionally been managed with open surgery or percutaneous antegrade
      endopyelotomy. PATIENTS AND METHODS: From November 2002 to April 2005, 55
      patients had RALP for PUJO; eight of these had concomitant renal calculi. Stone
      burden and location were assessed with a preoperative radiological examination.
      Before completing the PUJO repair, one robot working arm (cephalad one) was
      temporarily undocked to allow passage of a flexible nephroscope into the renal
      pelvis and collecting systems under direct vision. Stones were extracted with
      graspers or basket catheters and removed via the port. The surgical-assistant
      port in the subxiphoid area was used to introduce laparoscopic suction and other
      instruments. RESULTS: The Anderson-Hynes dismembered pyeloplasty was the
      preferred reconstructive technique in all patients. Operations were completed
      robotically with no conversions to open surgery. All patients were rendered stone
      free, confirmed by imaging, and there were no intraoperative or delayed
      complications during a mean (range) follow-up of 12.3 (4-22) months. The mean
      operative time was 275.8 min, 61.7 min longer than in patients who did not have
      concomitant stone removal. CONCLUSIONS: Concurrent stone extraction and PUJO
      repair can be successful with RALP. Operative times are longer than in patients
      with isolated PUJO repair, but this is to be expected as there is an additional
      procedure.

PMID- 16287460
TI  - Treatment of symptomatic simple renal cysts by percutaneous aspiration and
      ethanol sclerotherapy.
AB  - OBJECTIVE: To report our experience with the use of 95% ethanol as sclerotherapy
      for symptomatic simple renal cysts. PATIENTS AND METHODS: Sixty patients with 64
      symptomatic simple renal cysts were treated by ultrasonography (US)-guided
      percutaneous aspiration and injection of 95% ethanol (31 men and 29 women, mean
      age 46 years, SD 22). The main presentation was renal pain in 34 patients, renal
      mass in nine, hypertension in 11 and haematuria in six; 24 cysts were on the
      right, 32 on the left and four bilateral. Patients were evaluated after 1 month
      and then every 6 months by clinical assessment, US and intravenous urography.
      Success was defined as complete when there was total ablation of the cyst and
      partial when there was a recurrence of less than half the original cyst volume
      with the resolution of symptoms. Failure was defined as the recurrence of more
      than half of cyst volume and/or persistent symptoms. RESULTS: After aspiration
      and ethanol sclerotherapy, there was microscopic haematuria in two patients and
      low-grade fever (<38.3 degrees C) in two, but no major complications. During a
      mean (range) follow-up of 19 (14-40) months there was complete cyst ablation in
      54 cysts and partial resolution in 10. Pain disappeared or was much improved in
      all patients. After cyst ablation hypertension was well controlled with no
      medication in all 11 hypertensive patients and haematuria disappeared in all six
      affected patients. CONCLUSIONS: Ethanol sclerotherapy for symptomatic simple
      renal cysts is simple, minimally invasive and highly effective. We recommend it
      as the first therapeutic option in these patients.

PMID- 16287461
TI  - Persistent and occasional nocturnal enuresis in orthotopic urinary diversion: is
      there a urodynamic difference?
AB  - OBJECTIVE: To establish urodynamic criteria differentiating between men with a
      radical cystoprostatectomy and ileal neobladder who are persistently enuretic and
      those who are occasionally enuretic. PATIENTS AND METHODS: Fifty enuretic men at
      least 1 year after a radical cystoprostatectomy and ileal neobladder (hemi-Kock
      or 'W' neobladders) were divided into two groups according to the persistence of
      their complaint; 17 men were persistently enuretic (nightly) and 33 were
      occasionally enuretic (<3 episodes/week). Both groups were compared with 50 fully
      continent men with similar reservoirs. Uroflowmetry, enterocystometry and
      urethral pressure profilometry were carried out according to International
      Continence Society standards and terminology. RESULTS: Both enuretic groups had
      significantly higher residual urine volumes, pressure at mid-capacity and at
      maximum enterocystometric capacity, amplitude of uninhibited contractions, and
      lower compliance than continent men. Men with occasional enuresis also had a
      significantly higher frequency and duration of uninhibited contractions than
      continent men. Men with persistent enuresis had significantly lower average and
      maximum urinary flow rates than continent men, and significantly lower functional
      urethral length and maximum urethral pressure. Uroflowmetric and urethral
      pressure differences were dissimilar between men with occasional enuresis and
      controls. CONCLUSION: Enuretic men had significantly higher residual urine
      volumes and enterocystometric pressure variables than continent men. Men with
      persistent enuresis had significantly lower flow rates and less urethral
      resistance. Pharmacological inhibition of reservoir contraction and/or management
      of residual urine by clean intermittent catheterization before sleep might cure
      occasional enuresis.

PMID- 16287462
TI  - Genetic susceptibility to prostate cancer.

PMID- 16287463
TI  - ATP- and adenosine-induced relaxation of the smooth muscle of the pig urethra.
AB  - OBJECTIVES: To investigate relaxation mechanisms for ATP and adenosine in the pig
      urethra, together with the possible role of ATP in nerve-evoked urethral
      relaxations, as ATP is thought to cause bladder smooth muscle contraction via P2X
      receptors, whereas relaxation is mediated via G-protein coupled P2Y receptors,
      and ATP may also induce relaxation via breakdown to adenosine. MATERIALS AND
      METHODS: Circular muscle strips from the female pig urethra were mounted in
      tissue baths to record force; the effects of increasing concentrations of 1-300
      microM ATP, the P2-receptor agonist 2-methylthioATP (2-MeSATP), adenosine, the
      stable adenosine-analogue, 5'(N-ethylcarboxamido) adenosine (NECA), ADP, uridine
      triphosphate (UTP) and alpha,beta-methylene-ATP were assessed on the
      spontaneously developed tone. Responses to ATP were further assessed in the
      presence of G-protein activator guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS; 1
      10 microM), the G-protein inhibitor guanosine 5'-O-(2-thio-diphosphate)
      (GDPbetaS; 10-100 microM), suramin (1-100 microM), the ecto-ATPase inhibitor 6
      N,N-diethyl-beta-gamma-dibromomethylene-D-adenosine-5-triphosphate (ARL 67156, 10
      100 microM), and the suggested P2Y receptor antagonist, reactive blue-2 (1-100
      microM). The effect of the adenosine (P1) receptor antagonist 8-(p
      sulphophenyl)theophylline (8-SPT, 1-100 microM) on responses to adenosine, and
      the effects of the adenosine reuptake inhibitor S(p-nitrobenzyl)-6-thioinosine
      (NBTI, 1-100 microM) on responses to adenosine and ATP were also assessed.
      Responses to electrical field stimulation (EFS, 12 and 30 Hz) in the presence of
      phentolamine (1 microM), scopolamine (1 microM) and N omega-nitro-L-arginine (0.3
      mM) were studied before and after treatment with GTPgammaS, GDPbetaS, suramin,
      reactive blue-2 and ARL 67156. RESULTS: Strips were relaxed in a concentration
      dependent manner by exogenously administered ATP and 2-meSATP, the relaxations
      being slowly developing and long-lasting. The relaxant effect evoked by both
      agonists at 300 microM amounted to about half of the spontaneously developed
      tone. The relaxation evoked by ATP was not significantly affected by GTPgammaS,
      GDPbetaS, suramin, ARL 67156 or reactive blue-2. Adenosine induced a
      concentration-dependent relaxation of the smooth muscle tone, reaching a maximum
      of approximately 70% at 300 microM, whereas 300 microM NECA only relaxed the
      preparations by approximately 35%. The adenosine-induced relaxation was not
      affected by treatment with 8-SPT. However, NBTI (1 microM) significantly reduced
      the relaxation evoked by 300 microM adenosine. ADP relaxed the smooth muscle tone
      by approximately 40% (300 microM). There was no response to UTP, and the effect
      of alpha,beta-methylene-ATP was negligible (5% relaxation at 100 microM). EFS
      caused slowly developing and long-lasting relaxations that were unaffected by
      GTPgammaS, GDPbetaS, suramin, reactive blue-2 and ARL 67156. CONCLUSIONS: These
      results suggest that exogenous ATP and adenosine relax the smooth muscle of the
      pig urethra in a manner similar to that evoked by electrical stimulation of
      nerves, although there was no evidence for involvement of a definable P2Y
      receptor subtype in these relaxations.

PMID- 16287464
TI  - Changes in bladder nerve-growth factor and p75 genetic expression in
      streptozotocin-induced diabetic rats.
AB  - OBJECTIVE: To assess changes associated with diabetes in urinary bladder nerve
      growth factor (NGF) and NGF receptor p75NTR expression using a streptozotocin
      (STZ)-induced diabetic rat model. MATERIALS AND METHODS: Male Wistar rats (32)
      were divided into four equal groups: group I, vehicle-treated normal rats; group
      II, vehicle-treated 9-week STZ-diabetic rats; group III, insulin-treated 9-week
      STZ-diabetic rats; group IV, phlorizin-treated 9-week STZ-diabetic rats. Bladder
      NGF levels were measured by enzyme-linked immunosorbent assay. Expressions of the
      mRNAs that encoded NGF and NGF receptor p75NTR in the rat bladder were evaluated
      using reverse transcription-polymerase chain reaction. RESULTS: The mean (SEM)
      NGF level in the STZ-diabetic rat bladder was significantly lower than in the
      control group, at 56.56 (8.28) and 84.33 (11.05) pg/microg protein, respectively
      (P < 0.01). The mRNA expressions of bladder NGF and p75NTR in the diabetic rats
      were significantly lower than in the control group (P < 0.05 and <0.001,
      respectively). Treatment with either insulin or phlorizin restored the normal
      blood sugar level; moreover, the bladder NGF levels and the expressions of both
      NGF and p75NTR mRNAs were normal. CONCLUSION: The decrease in the genetic
      expression of NGF and p75NTR might be responsible for the pathogenesis of
      diabetic cystopathy while hyperglycaemia is part of the cause of these changes.

PMID- 16287465
TI  - Protective effects of grape suspension on in vivo ischaemia/reperfusion of the
      rabbit bladder.
AB  - OBJECTIVE: To investigate the potential protective effect of a grape suspension
      in a rabbit model of in vivo bilateral ischaemia/reperfusion (I/R), which is a
      causal factor in obstructive bladder dysfunction. MATERIALS AND METHODS: Six
      groups of four New Zealand White rabbits were treated by twice-daily gavage with
      aqueous grape suspension (groups 1-3) or sugar-water vehicle (groups 4-6) for 3
      weeks. Groups 1 and 4 then received bilateral ischaemia for 2 h, and groups 2 and
      5 received bilateral ischaemia for 2 h and reperfusion (recovery) for 1 week.
      Groups 3 and 6 were controls (sham-operated). The effects on cystometry, in vitro
      contractile responses, and morphology were evaluated. RESULTS: Ischaemia resulted
      in significant reductions in the contractile responses to all forms of
      stimulation in vehicle-fed rabbits, whereas there were no reductions in grape-fed
      rabbits. Contractile responses were significantly reduced in both I/R groups, but
      significantly more in vehicle-fed than in grape-fed rabbits. Immunohistochemical
      studies showed less hypoxia in the bladders of grape-fed rabbits than in vehicle
      fed rabbits for both ischaemia-only and I/R groups. CONCLUSIONS: Feeding rabbits
      with grape suspension provided significant protection against the hypoxic effects
      of bilateral ischaemia and I/R.

PMID- 16287467
TI  - Novel and simple method for isolating autologous mesothelial cells from the
      tunica vaginalis.
AB  - OBJECTIVE: To report the development of a new method of isolating autologous
      mesothelial cells from the tunica vaginalis that are easily obtained and
      generally free from the effects of abdominal cancer, and to investigate whether
      transplanting these mesothelial cells is effective in preventing postoperative
      adhesions. MATERIALS AND METHODS: The tunica vaginalis was resected from male
      Lewis rats, and mesothelial cells were collected by enzymatic disaggregation. To
      investigate the efficacy of mesothelial cells in preventing adhesion, harvested
      cells were transplanted into a rat intestinal hernia adhesion model. RESULTS:
      Cells isolated from the tunica vaginalis were homogenous, polygonal when
      confluent, expressed cytokeratin and vimentin, and the cell surface was covered
      with microvilli, which is the characteristic appearance of endogenous mesothelial
      cells. The transplantation of autologous mesothelial cell sheets reduced
      peritoneal adhesion. CONCLUSION: We developed a new method of obtaining
      autologous mesothelial cells from the tunica vaginalis. These cells may provide a
      valuable option for treating patients at risk of postoperative adhesions.

PMID- 16287466
TI  - Effect of glycine on recovery of bladder smooth muscle contractility after acute
      urinary retention in rats.
AB  - OBJECTIVE: To investigate the effects of glycine on the recovery of bladder
      smooth muscle contractility after acute urinary retention. MATERIALS AND METHODS:
      Bladder overdistension was induced in Sprague-Dawley rats by an infusion of
      saline (twice the threshold volume), maintained for 2 h. From 15 min before
      emptying of the bladder until 2 h after, saline or glycine solution was infused
      i.v. At 30 min, 2 h and 1 week after bladder emptying, samples of bladder tissue
      were taken for muscle strip study, malondialdehyde (MDA) assay, ATP assay,
      Western blotting for apoptosis-related molecules (Bcl-2, Bax, Caspase-3), and
      histological analysis including terminal deoxynucleotidyl transferase-mediated
      nick-end labelling staining. The results were compared among normal control,
      saline-treated and glycine-treated rats. RESULTS: In the glycine-treated group,
      muscle strip contractile responses induced by electrical-field stimulation and
      carbachol were both significantly greater at 1 week after bladder emptying than
      in the saline-treated group. The results of the ATP assay appeared to correspond
      with those of the muscle strip study. The saline-treated group had significantly
      higher MDA levels at 30 min after bladder emptying than the glycine-treated
      group. At 2 h after bladder emptying, there was significantly more apoptosis and
      greater leukocyte infiltration in the saline-treated group than in the glycine
      treated group. While pro-apoptotic Bax and caspase-3 were down-regulated, Bcl-2
      was up-regulated in the glycine-treated group. CONCLUSION: Glycine infusions
      might improve the contractile responses of bladder smooth muscle after acute
      urinary retention by reducing oxidative damage and apoptosis.

PMID- 16287468
TI  - Urological flood or drought in 2006?

PMID- 16287469
TI  - Laparoscopic management of complicated urachal remnants.
AB  - OBJECTIVE: To report our experience with a laparoscopic approach to managing
      symptomatic urachal anomalies. PATIENTS AND METHODS: Five patients (median age 19
      years, range 2-43) had a laparoscopic excision of a complicated urachal remnant
      between 2001 and 2004. Three ports were routinely used, although their
      positioning varied as our technique developed with experience. The urachal
      remnant was dissected from the umbilicus to the bladder dome and then removed
      intact. RESULTS: All five operations had no serious immediate complications and
      minimal blood loss. One patient developed a small peri-umbilical haematoma after
      surgery and another had a persistent umbilical discharge at follow-up, and
      required open excision of residual remnant tissue. CONCLUSIONS: The laparoscopic
      approach appears to be a safe and effective alternative to open surgery for this
      condition. Despite the slight risk of incomplete excision, the reduced morbidity
      of this procedure and better cosmetic result would appear advantageous.

PMID- 16287470
TI  - Pedicled pubic phalloplasty in females with gender dysphoria.

PMID- 16287471
TI  - The incidence and treatment of lymphoceles after radical retropubic
      prostatectomy.

PMID- 16287472
TI  - The management of penile fracture based on clinical and magnetic resonance
      imaging findings.

PMID- 16287473
TI  - Outcome from percutaneous nephrolithotomy in patients with spinal cord injury,
      using a single-stage dilator for access.

PMID- 16287474
TI  - Cystoscopic removal of a JJ stent using a suture 'lasso'.

PMID- 16287475
TI  - In vivo and in vitro response of corpus cavernosum to phosphodiesterase-5
      inhibition in the hypercholesterolaemic rabbit.

PMID- 16287476
TI  - Intussuscepted ileal flap valve for revisional surgery.

PMID- 16287477
TI  - Handicaps and the development of skills between childhood and early adolescence
      in young people with severe intellectual disabilities.
AB  - BACKGROUND: While a number of studies have examined the development of skills in
      children with intellectual disabilities (ID), most have been cross-sectional,
      most have been concerned with particular syndromes such as Down's syndrome or
      autism and few have attempted to identify factors associated with improvements in
      skills. METHODS: From a sample of 111 children with severe ID who had been
      identified from the registers of six special schools at 4-11 years of age, 82
      were traced and reassessed 5 years later at the age of 11-17 years. On both
      occasions, information on the children's handicaps and skills was collected by
      interviewing their main carers using a shortened version of the Vineland Adaptive
      Behaviour Scales and the Disability Assessment Schedule. RESULTS AND CONCLUSIONS:
      There were small but statistically significant improvements in Vineland age
      equivalent communication and daily living skills scores, but not in Vineland
      Socialization scores, over the 5-year period of follow-up. This pattern of
      improvement was observed in most aetiological subgroups. Improvement in skills
      was greatest in younger children, and was associated with reductions in behaviour
      problems and in levels of parental stress. In spite of the improvements in age
      equivalent scores, Vineland standard scores showed significant declines over the
      same period of time, indicating that the improvements observed were smaller than
      would be expected in a general population sample of children of the same age. The
      dangers of using standard scores or quotients to quantify the level of
      functioning of children with severe ID are highlighted.

PMID- 16287478
TI  - Empowerment in parents of school-aged children with and without developmental
      disabilities.
AB  - BACKGROUND: Despite the widespread use of the term 'empowerment' in clinical
      literature to describe both a desirable process and the outcome of service
      delivery, the term remains more of a theoretical than practical construct. This
      study examined the factors that contribute to empowerment in parents of school
      aged children with and without developmental disabilities (DD) using the Double
      ABCX model of family adaptation contrasted with the linear ACBX model. METHODS:
      Parents of children with (n = 100, 97% mothers) and without (n = 100, 98%
      mothers) DD completed questionnaires relating to child behaviour problems, parent
      stress and well-being, and formal and informal support. Structural equation
      modelling was used RESULTS: Parents of children with DD reported more child
      behaviour problems, more stress, less well-being and more social support than
      parents of children without DD. Structural equation modelling supported the ACBX
      model for both groups. A linear relationship was found in which parent well-being
      and resources mediated the relationship between the stressor (child behaviour
      problems) and the outcome (empowerment). CONCLUSIONS: The results of the current
      study support Hastings and Taunt's assertion in 2002, in that empowerment was
      adequately explained using a traditional model of family functioning. The
      significant prediction offered by the parent's resources points to the need to
      deliver services in a manner that is more family-centred. In the education
      system, this means providing parents with clear messages regarding the schools
      goals, clarifying the parent's rights and responsibilities, including the parent
      in planning and decision making, respecting their knowledge as caregivers and
      supporting their hopes for their child.

PMID- 16287479
TI  - A follow-up study of mortality, health conditions and associated disabilities of
      people with intellectual disabilities in a Swedish county.
AB  - BACKGROUND: In the planning of services and health care for individuals with
      intellectual disability (ID), information is needed on the special requirements
      for habilitation and medical service and associated disabilities. MATERIAL AND
      METHODS: An unselected consecutive series of 82 adult persons with ID was
      studied. The medical examination consisted of the individual's health condition,
      associated impairments and disabilities. Medical and habilitation services and
      support were studied. RESULTS: The results indicated that 71% of the persons in
      the series had severe and 29% mild ID. Forty-seven per cent of the persons with
      severe ID and 35% of those with mild ID had one or more additional central
      nervous system (CNS) disabilities. Of the persons with ID, 99% had access to a
      family doctor and 84% attended regular health visits. Notably, half of persons
      were referred to a specialist examination as a consequence of their present
      medical examination. Half of the persons with mental health problems were
      previously undiagnosed and only a few of these had access to a psychiatrist.
      CONCLUSION: Our study clearly demonstrates the magnitude and importance of
      neurological and psychiatric impairments in ID. The findings suggest a strong
      need for multidisciplinary health service.

PMID- 16287480
TI  - Stability and change in cognitive ability over the life span: a comparison of
      populations with and without Down's syndrome.
AB  - BACKGROUND: Longitudinal studies show that in the general population IQ declines
      with age: early and rapidly in the case of performance IQ, later and more slowly
      in the case of verbal IQ. These populations have not apparently included people
      with intellectual disabilities (ID). METHOD: A literature search identified 11
      studies, some cross-sectional and others longitudinal, which provided data on a
      variety of verbal and performance tests, over periods from 3 to 19 years, on
      older people with ID. Following statistical advice the results from the different
      tests were converted into the equivalent of, for verbal scores, British Picture
      Vocabulary Scale, and for performance scores, Leiter International Performance
      Scale, raw scores. Percentage change between earlier and later scores was then
      calculated. RESULTS: With one exception the studies considered tend to show
      verbal ability declining relatively more, and performance ability declining
      relatively less, than has been shown to occur in the general population.
      Potential confounding factors, such as population attrition, cohort effects,
      etc., are thought not to have affected these results. CONCLUSIONS: The pattern of
      change with age in verbal and performance ability appears different in people
      with ID from that seen in the general population. Some possible reasons for this
      difference are discussed.

PMID- 16287481
TI  - Children with Prader-Willi syndrome vs. Williams syndrome: indirect effects on
      parents during a jigsaw puzzle task.
AB  - BACKGROUND: Genetic disorders predispose individuals to exhibit characteristic
      behaviours, which in turn elicit particular behaviours from others. In response
      to the strength of Prader-Willi syndrome (PWS) and weakness of Williams syndrome
      (WS) in visual-spatial tasks such as jigsaw puzzles, parents' behaviours can be
      affected by their child's level of puzzle ability or syndrome diagnosis. METHODS:
      Children were asked to complete two jigsaw puzzles (one with the experimenter and
      the other with the parent) for 5 min each. Frequencies of parental helping and
      reinforcement behaviours, along with ratings of parental directiveness, were
      examined as parents interacted with their children on a jigsaw puzzle task.
      Within each aetiological group, correlates of parental behaviours with child
      characteristics were also examined. RESULTS: Compared to parents of children with
      PWS, parents of children with WS engaged in a more directive style of
      interaction, and provided more help and reinforcement. Relative to parents of
      children with higher puzzle abilities (from both aetiologies), parents of
      children with lower abilities also showed the same pattern. Both the child's
      aetiology and puzzle abilities were important in predicting parents'
      directiveness and helping and reinforcement behaviours. Within the PWS group,
      parents' behaviours correlated negatively with the child's puzzle abilities and
      general cognitive functioning; no such relations occurred in the WS group.
      CONCLUSIONS: Parents' behaviours were affected by both the child's diagnosis and
      actual puzzle abilities, suggesting important implications for understanding and
      intervening with parents and children with different genetic syndromes.

PMID- 16287482
TI  - Correlation between Musashi-1 and c-hairy-1 expression and cell proliferation
      activity in the developing intestine and stomach of both chicken and mouse.
AB  - Musashi-1 (Msi-1) is an RNA-binding protein that plays key roles in the
      maintenance of neural stem cell states and in their differentiation into neural
      cells. Msi-1 has also been proposed as a candidate marker gene of mammalian
      intestinal stem cells and their immediate lineages. In this study, we examined
      Msi-1 expression in the small intestine and the stomach of both chicken and mouse
      during embryonic, fetal and postnatal development. In addition, we analyzed the
      expression of c-hairy-1, a chicken homologue of mouse Hes1, and assessed the
      proliferative activity of the cells expressing both of these factors.
      Significantly, during the development of these digestive organs in both species
      Msi-1 expression showed dynamic changes, suggesting that it is important for
      digestive organ development, particularly for epithelial differentiation. Based
      on our observations of the expression patterns of Msi-1 and c-hairy-1 in the
      adult small intestine, we speculate that Msi-1 is also a stem cell marker of the
      chicken small intestinal epithelium.

PMID- 16287483
TI  - Identification of asymmetrically localized transcripts along the animal-vegetal
      axis of the Xenopus egg.
AB  - In many organisms, proper embryo development depends on the asymmetrical
      distribution of mRNA in the cytoplasm of the egg. Here we report comprehensive
      screening of RNA localized in the animal or vegetal hemisphere of the Xenopus
      egg. Macroarrays including over 40,000 independent embryonic cDNA clones,
      representing at least 17,000 unigenes, were differentially hybridized with
      labeled probes synthesized from the mRNA of animal or vegetal blastomeres. After
      two rounds of screening, we identified 33 clones of transcripts that may be
      preferentially distributed in the vegetal region of the early stage embryo, but
      transcripts localized in the animal region were not found. To assess the array
      results, we performed northern blot and quantitative real-time reverse
      transcription-polymerase chain reaction analysis. As a result, 21 transcripts of
      the 33 were confirmed to be localized in the vegetal region of the early stage
      embryo. Whole-mount in situ hybridization analysis revealed that 11 transcripts,
      including 7 previously reported genes, were localized in the vegetal hemisphere
      of the egg. These 11 transcripts were categorized into three groups according to
      their expression patterns in the egg. The first group, which contained four
      transcripts, showed uniform expression in the vegetal hemisphere, similar to
      VegT. The second group, which contained three transcripts, showed gradual
      expression from the vegetal pole to the equator, similar to Vg1. The last group,
      which contained three transcripts, was expressed at the germ plasm, similar to
      Xdazl. One transcript, Xwnt11, showed both the second and the third expression
      patterns.

PMID- 16287484
TI  - Extraocular dorsal signal affects the developmental fate of the optic vesicle and
      patterns the optic neuroepithelium.
AB  - Dorsal-ventral (DV) specification in the early optic vesicle plays a crucial role
      in the proper development of the eye. To address the questions of how DV
      specification is determined and how it affects fate determination of the optic
      vesicle, isolated optic vesicles were cultured either in vitro or in ovo. The
      dorsal and ventral halves of the optic vesicle were fated to develop into retinal
      pigment epithelium (RPE) and neural retina, respectively, when they were
      separated from each other and cultured. In optic vesicles treated with
      collagenase to remove the surrounding tissues, the neuroepithelium gave rise to
      cRax expression but not Mitf, suggesting that surrounding tissues are necessary
      for RPE specification. This was also confirmed in in ovo explant cultures.
      Combination cultures of collagenase-treated optic vesicles with either the dorsal
      or ventral part of the head indicated that head-derived factors have an important
      role in the fate determination of the optic vesicle: in the optic vesicles co
      cultured with the dorsal part of the head Mitf expression was induced in the
      neuroepithelium, while the ventral head portion did not have this effect. The
      dorsal head also suppressed Pax2 expression in the optic vesicle. These
      observations indicate that factors from the dorsal head portion have important
      roles in the establishment of DV polarity within the optic vesicle, which in turn
      induces the patterning and differentiation of the neural retina and pigment
      epithelium.

PMID- 16287486
TI  - Wound healing ability of Xenopus laevis embryos. I. Rapid wound closure achieved
      by bisectional half embryos.
AB  - We examined wound closure in 'half embryos' produced by the transverse bisection
      of Xenopus laevis embryos at the primary eye vesicle stage. Both the anterior-
      and posterior-half embryos survived for more than 6 days, and grew into 'half
      tadpoles'. Histology and videomicroscopy revealed that the open wound in the half
      embryo was rapidly closed by an epithelial sheet movement in the wound marginal
      zone. The time-course of wound closure showed a downward convex curve: the wound
      area decreased to one-fifth of the original area within 30 min, and the wound
      continued to contract slowly thereafter. The rapidity of closure of the epidermis
      as well as the absence of inflammatory cells are typical features of an embryonic
      type of wound healing. There was a dorso-ventral polarity in the motility of the
      epidermis: the wound was predominantly closed by the ventral and lateral
      epidermis. The change in the contour of the wound edge with time suggested a
      complex mechanism involved in the wound closure that could not be explained only
      by the purse-string theory. The present experimental system would be a unique and
      useful model for analyses of cellular movements in the embryonic epithelia.

PMID- 16287485
TI  - Smad7 induces G0/G1 cell cycle arrest in mesenchymal cells by inhibiting the
      expression of G1 cyclins.
AB  - The major Smad pathways serve in regulating the expression of genes downstream of
      TGFbeta signals. In this study, we examined the effects of sustained Smad7
      expression in cultured cells. Interestingly, Smad7 caused various mesenchymal
      cells, including NIH3T3 fibroblast and ST2 bone-marrow stromal cells, to undergo
      a marked morphological alteration into a flattened cell shape, but kept them
      alive for as long as 60 days. Furthermore, Smad7 arrested the proliferation of
      the cells even before they reached confluence. These cells became quiescent in
      G0/G1 phase and accumulated a hypophosphorylated form of retinoblastoma. The
      cytostatic effect of Smad7 was closely associated with a preceding decrease in
      the levels of G1 cyclins, such as cyclin D1 and cyclin E. Accordingly, ectopic
      cyclin E was able to overcome the Smad7-induced arrest of proliferation. These
      results indicate that Smad7 functions upstream of G1 cyclins and suggest a novel
      role for Smad7 as an antiproliferative factor. In contrast to the growth of
      mesenchymal cells, that of epithelial cells was little susceptible to Smad7. The
      present findings raise the possibility that a link between Smad7 and the G1 to S
      phase transition may also contribute to the cell cycle control by certain Smad7
      inducing stimuli in a cell-type-dependent fashion.

PMID- 16287487
TI  - Wound healing ability of Xenopus laevis embryos. II. Morphological analysis of
      wound marginal epidermis.
AB  - We previously showed that bisectional wounds made in Xenopus laevis embryos at
      the primary eye vesicle stage were rapidly closed. In this study, microscopic
      analyses, including scanning electron microscopy, on the morphology of the
      epidermis were conducted during wound closure in the half embryos. Bright
      fluorescence of Texas red-phalloidin showing actin filaments started to be
      visualized at the cut edge 10 min after wounding. It increased with time, forming
      a distinguished, though discontinuous, bundle along the wound margin. The wound
      closure was completely inhibited by 20 microm cytochalasin B, and almost
      completely by 50 mm 2,3-butanedione 2-monoxime, an inhibitor to myosin ATPase
      activity. Scanning electron microscopy revealed that the outer epidermal cells
      became extensively elongated in the radial direction, and the contour of the
      closing wound edge did not become smoother but remained ragged. Thus, a
      representative embryonic type of wound closure may be driven in Xenopus embryos
      by a complex mechanism, involving not only the actin 'purse-string' but also an
      inward movement of individual cells. Anyhow, the wound closure is a movement of
      the epidermal sheet maintaining cell-cell contact, and not involving locomotion
      of single cells separated from the wound edge.

PMID- 16287488
TI  - Endothelin-3 controls growth of colonic epithelial cells by mediating epithelial
      mesenchymal interaction.
AB  - It has been repeatedly reported that endothelin-3 (ET-3) is expressed by
      gastrointestinal mesenchymes, and that paracrine signaling between ET-3 and its
      receptor plays an essential role in controlling differentiation of the enteric
      nervous system in the gut, especially in the colon. However it remains to be
      solved whether ET-3 plays a role in regulating the growth of gastrointestinal
      epithelial cells. We have previously reported culture systems for forestomach,
      glandular stomach and duodenal epithelial cells, but a system for colonic
      epithelial cells has not been established. In the present study, we examined
      optimal culture conditions for colonic epithelial cells, and examined whether ET
      3 affects the growth of gastrointestinal epithelial cells, with special reference
      to colonic cells. We found that ET-3 dose-dependently and region-specifically
      stimulated their growth in primary culture: colonic epithelial cells were most
      responsive, followed by duodenal and glandular stomach epithelial cells. Reverse
      transcription-polymerase chain reaction analysis showed that ET-3 and a receptor
      for ET-3 were expressed by both colonic mesenchymes and epithelia, but the levels
      were much higher in mesenchymes than in epithelia. These results suggest that ET
      3 plays an important role in the growth control of colonic epithelial cells,
      possibly by mediating epithelial-mesenchymal interactions.

PMID- 16287489
TI  - Simultaneous imaging of membrane antigen and the corresponding chromosomal locus
      in pathology archives.
AB  - A new procedure for the simultaneous staining of membranous antigens, such as
      tyrosine kinase-type cell surface receptor HER2 (c-erbB2), and the corresponding
      chromosome (chromosome 17 for c-erbB2) in the same cell for use in examining
      pathology archives is presented. A multistep procedure involving microwave
      assisted fluorescence in situ hybridization and immunofluorescence yielded cell
      images having c-erbB2 on the membrane and genomic signals from the chromosome 17
      centromere and the c-erbB2 locus. Furthermore, a combination of microwave
      assisted chromogenic in situ hybridization and immunohistochemistry found
      colorized signals from both chromosome 17 centromere in the nuclei and c-erbB2 on
      the membranes of individual cells. Quantitative image analysis further confirmed
      the presence of a significantly stronger c-erbB2 immunoreactivity on cells
      containing three or more signals from chromosome 17 than from those with less
      than three signals. It was possible to extend the constellation of cell surface
      markers and corresponding chromosomes or locus-specific makers to several other
      genes including CDH1. In this case, the disappearances of CDH1 expression, a CDH1
      locus signal, and a centromere enumeration probe (CEP) 16 signal were
      simultaneously demonstrated in the less-adhesive tumor cells. Thus, it is
      believed that this procedure might pave the way for exploiting pathology archives
      for the genotype-phenotype analysis of individual cells.

PMID- 16287490
TI  - Expression of KIT, EGFR, HER-2 and tyrosine phosphorylation in undifferentiated
      thyroid carcinoma: implication for a new therapeutic approach.
AB  - The KIT, epidermal growth factor receptor (EGFR) and HER-2 oncoproteins have
      tyrosine kinase activity and are molecular targets in human cancer therapy. To
      clarify the significance of KIT, EGFR, and HER-2 in undifferentiated thyroid
      carcinoma (UTC), the expression of these receptors and tyrosine phosphorylation
      was examined immunohistochemically in resected cases of UTC and papillary thyroid
      carcinoma (PTC). KIT, EGFR, and HER-2 were also examined at the protein and mRNA
      levels in five UTC cell lines. KIT expression (1+), EGFR overexpression (2+/3+),
      HER-2 expression (1+), and tyrosine phosphorylation were detected
      immunohistochemically in 40%, 70%, 10%, and 50% of the 10 UTC. In 20 PTC, KIT,
      EGFR, and HER-2 were not detected, but tyrosine phosphorylation was detected in
      25% of cases. In the five UTC cell lines, KIT expression (1+), EGFR
      overexpression (3+), HER-2 expression (1+), and tyrosine phosphorylation were
      detected immunocytochemically in 60%, 100%, 20%, and 40%, respectively. Western
      blot analysis did not detect KIT expression, but did detect EGFR and HER-2
      expression in all five cell lines. Real-time polymerase chain reaction detected
      KIT mRNA in two of the cell lines (40%), EGFR in five (100%), and HER-2 in three
      (60%). The present findings suggest that EGFR overexpression was involved in the
      proliferation and development of UTC and was frequently accompanied by tyrosine
      phosphorylation. Expression of KIT and HER-2 appeared to be weak but significant,
      suggesting a possible role in the development of UTC. Molecular therapies
      targeting KIT, EGFR, HER-2, and/or tyrosine phosphorylation might be indicated
      for UTC.

PMID- 16287491
TI  - Molecular pathological subclassification of mucinous adenocarcinoma of the
      colorectum.
AB  - The purpose of the present report was to examine the possibility of molecular
      pathological subtyping of mucinous adenocarcinomas (MAC) of the colorectum.
      Thirty-five formalin-fixed and paraffin-embedded MAC specimens of the colorectum
      were analyzed. Genetic alterations of p53 gene and microsatellite instability
      (MSI) as well as immunohistochemical analysis of mucin subtypes (human gastric
      mucin (HGM), anti-mucin monoclonal antibody recognizing gastric gland mucous
      cells-1, MUC2, CD10) and expression levels of human mutL homolog 1 (hMLH1), p53
      and Ki-67 were performed. According to MSI and p53 status, these tumors were
      subclassified into three groups: mutator-type tumors with a high frequency of MSI
      (20%), suppressor/p53-type tumors with p53 mutation, p53 overexpression or loss
      of heterozygosity of D17S250 (an adjacent locus to p53; 40%) and the unclassified
      tumors (40%). The suppressor/p53-type tumors had a significant association with
      distal colon location (P = 0.019), venous invasion (P = 0.002), extent of lymph
      node metastasis (P = 0.007) and higher tumor stage (P = 0.018). In contrast,
      mutator-type tumors had frequent expression of HGM (P = 0.005) and prominent
      lymphocytic infiltration at the advancing front of the tumor (P = 0.005). These
      results indicate that MAC of the colorectum could be subclassified according to
      molecular pathological background, reflecting distinct clinicopathological and
      phenotypic characteristics.

PMID- 16287492
TI  - Can cytological findings predict intraductal spread of breast cancer?
      Histopathological case-control study.
AB  - An important predictive factor for local recurrence after breast-conserving
      therapy is the state of the surgical margin. In order to obtain a negative
      surgical margin, the present case-control study was conducted to determine
      whether the extent of ductal spread can be estimated from the information
      obtained by fine-needle aspiration (FNA). Samples from 69 cases of extensive
      ductal spread (EDS) in which it was thought that cancer cells had remained in the
      residual breast when the lumpectomy was performed with 2 cm margins, were
      retrieved and compared with 62 cases having almost the same clinical and
      pathological tumor size. The cases of EDS included a significantly larger number
      of papillotubular carcinomas (37%vs 13%, P = 0.004) and displayed a high nuclear
      atypia (42%vs 26%, P = 0.001). We could estimate the same tendency with
      cytological studies. Cancer cells with cohesive papillary-like clusters
      suggesting papillotubular carcinoma and with a large nuclear diameter were
      significantly more numerous in cases of EDS (P < 0.01). In conclusion, EDS can be
      determined by estimating histological type via cytodiagnosis and measuring the
      nuclear diameter of cancer cells.

PMID- 16287493
TI  - Ectopic cervical anaplastic ependymoma.
AB  - Ependymomas generally arise in the central nervous system (CNS), although rare
      primary extraneural ependymomas have been observed. Reported herein for the first
      time is the case of a patient with primary ectopic cervical anaplastic
      ependymoma. The tumor was found in the right neck root region of a 35-year-old
      man. No additional tumor was found in the CNS or in other parts of the body. The
      patient received surgery and post-surgical local radiotherapy. Microscopically,
      the tumor consisted of round to oval cells with fine chromatin, distinct
      nucleoli, moderate nuclear atypia and numerous mitoses (>25/10 high-power fields)
      in a densely cellular growth pattern with characteristic fibrillary cytoplasm and
      formation of perivascular pseudorosettes. By immunohistochemistry, the tumor
      cells were positive for glial fibrillary acidic protein, epithelial membrane
      antigen (EMA), vimentin and S-100 protein. EMA staining showed a membranous as
      well as a paranuclear pattern of immunoreactivity. Electron microscopic studies
      revealed that tumor cells form micro rosettes, into which microvilli and cilia
      projected. The diagnosis was World Health Organization grade III anaplastic
      ependymoma. There is no evidence of local tumor recurrence or distant metastasis
      after 30 months follow up. The present case adds yet another unique example to
      the already diverse spectrum of head and neck neoplasms encountered in surgical
      pathology.

PMID- 16287494
TI  - Histologically unique case of combined small cell and squamous cell carcinoma in
      a polypoid bronchial tumor.
AB  - Presented herein is a case of combined small cell and squamous cell carcinoma in
      a polypoid bronchial tumor, showing a histologically unique progression, in a 76
      year-old Japanese man. A bronchofiberscopic examination revealed that the
      bronchus (left B3) was occluded by the polypoid tumor. Biopsies were performed,
      and the pathological diagnosis was poorly differentiated squamous cell carcinoma.
      The patient consequently underwent a left upper lung lobectomy. The surgical
      specimen was described as a 24 x 8 x 8 mm soft tumor, emanating from the
      bronchial wall (left B3). Histologically, the tumor had two distinct components:
      (i) nearly the entire tumor was composed of atypical small round cells, with a
      high nuclear-cytoplasmic ratio, in the lamina propria, under the basement
      membrane; and (ii) the surface of the tumor was composed of poorly differentiated
      squamous cell carcinoma that had proliferated primarily above the basement
      membrane but there was also some proliferation, seen as island-like formations,
      below the basement membrane. The histological diagnosis was combined small cell
      and squamous cell carcinoma. It was suspected that poorly differentiated squamous
      cell carcinoma, generated in the bronchial epithelium, had caused small cell
      carcinoma resulting from neuroendocrine differentiation during its invasion into
      the lamina propria.

PMID- 16287496
TI  - Composite mucinous and granulosa cell tumor of the ovary.
AB  - A composite mucinous and granulosa cell tumor of the ovary in a 76-year-old woman
      is herein reported. At laparotomy this tumor proved to be a solid and cystic mass
      measuring 10 cm in greatest diameter. Many of the cysts were lined with a benign
      mucinous epithelium of the endocervical type, and solid areas contained a
      proliferation of granulosa cells. These two disparate components were intimately
      mixed. A theca cell component was also present in areas adjacent to the mucinous
      epithelium. The coexistence of mucinous and granulosa cell tumor is extremely
      rare and only four such cases have previously been reported in the literature,
      and the histogenesis of this tumor has not yet been elucidated. In the present
      case it is suggested that the granulosa cell element commenced as a reactive
      stromal hyperplasia in the wall of the pre-existing mucinous neoplasm and
      thereafter progressed to the point of producing a tumor-like mass or neoplastic
      changes.

PMID- 16287495
TI  - Solid pseudopapillary tumor of the pancreas with metastases to the lung and
      liver.
AB  - Presented herein is the case of a 41-year-old woman who was admitted to Teikyo
      University Hospital with abdominal and back pain. Clinical examination revealed a
      large mass of the pancreas and multiple nodules in the liver. After surgical
      resection of the pancreatic and liver tumors, liver nodules recurred repeatedly,
      and a solitary mass lesion occurred in the right lung. Grossly, the pancreatic
      tumor was large and partially cystic. Histologically, small and uniform tumor
      cells proliferated, having solid and pseudopapillary patterns. These pathological
      findings enabled a pathological diagnosis of solid pseudopapillary tumor (SPT) of
      the pancreas to be made. The pathological appearance of the liver and lung tumors
      was similar to that of the pancreatic tumor. This is the first report of a case
      of pancreatic SPT that showed lung metastasis. It should be kept in mind that
      pancreatic SPT may take such an aggressive clinical course, although they are
      usually benign in nature.

PMID- 16287497
TI  - Low-grade fibromyxoid sarcoma arising in the big toe.
AB  - Low-grade fibromyxoid sarcoma (LGFMS) is a rare tumor. Reported herein is a case
      of LGFMS arising in the big toe. The patient was a 58-year-old man who underwent
      excision of the tumor. The tumor was well-demarcated. Histologically, there were
      proliferating spindle-shaped tumor cells arranged in a whorled growth pattern,
      and the stroma showed hyalinized collagen bundles and a myxoid matrix. Nuclear
      mitotic figures were conspicuous in part. A large rosette-like structure with
      hyalinized stroma was found, which is characteristic of LGFMS. The differential
      diagnosis included tumor occurrence in adults; tending to arise in distal
      extremities; and having bland fibromyxoid histological features, such as fibroma
      of tendon sheath, low-grade myxofibrosarcoma and acral myxoinflammatory
      fibroblastic sarcoma. It was not possible to detect the FUS/CREB3L2 and
      FUS/CREB3L1 fusion genes from the formalin-fixed and paraffin-embedded tissue,
      although the histological features of the present case were typical of LGFMS.
      LGFMS may become more common with time, and unique cases may accumulate.

PMID- 16287498
TI  - A case of malignant solitary fibrous tumor of the prostate.

PMID- 16287499
TI  - Single and repeated moderate consumption of native or dealcoholized red wine show
      different effects on antioxidant parameters in blood and DNA strand breaks in
      peripheral leukocytes in healthy volunteers: a randomized controlled trial
      (ISRCTN68505294).
AB  - BACKGROUND: Red wine (RW) is rich in antioxidant polyphenols that might protect
      from oxidative stress related diseases, such as cardiovascular disease and
      cancer. Antioxidant effects after single ingestion of RW or dealcoholized RW
      (DRW) have been observed in several studies, but results after regular
      consumption are contradictory. Thus, we examined if single or repeated
      consumption of moderate amounts of RW or DRW exert antioxidant activity in vivo.
      METHODS: Total phenolic content and concentration of other antioxidants in
      plasma/serum, total antioxidant capacity (TEAC) in plasma as well as DNA strand
      breaks in peripheral leukocytes were measured in healthy non-smokers A) before,
      90 and 360 min after ingestion of one glass of RW, DRW or water; B) before and
      after consumption of one glass of RW or DRW daily for 6 weeks. DNA strand breaks
      (SB) were determined by single cell gel electrophoresis (Comet Assay) in
      untreated cells and after induction of oxidative stress ex vivo with H2O2 (300
      microM, 20 min). RESULTS: Both RW and DRW transiently increased total phenolic
      content in plasma after single consumption, but only RW lead to a sustained
      increase if consumed regularly. Plasma antioxidant capacity was not affected by
      single or regular consumption of RW or DRW. Effects of RW and DRW on DNA SB were
      conflicting. DNA strand breaks in untreated cells increased after a single dose
      of RW and DRW, whereas H2O2 induced SB were reduced after DRW. In contrast,
      regular RW consumption reduced SB in untreated cells but did not affect H2O2
      induced SB. CONCLUSION: The results suggest that consumption of both RW and DRW
      leads to an accumulation of phenolic compounds in plasma without increasing
      plasma antioxidant capacity. Red wine and DRW seem to affect the occurrence of
      DNA strand breaks, but this cannot be referred to antioxidant effects.

PMID- 16287500
TI  - Hispanic physicians' tobacco intervention practices: a cross-sectional survey
      study.
AB  - BACKGROUND: U.S. Hispanic physicians constitute a considerable professional
      collective, and they may be most suited to attend to the health education needs
      of the growing U.S. Hispanic population. These educational needs include tobacco
      use prevention and smoking cessation. However, there is a lack of information on
      Hispanic physicians' tobacco intervention practices, their level of awareness and
      use of cessation protocols, and the type of programs that would best address
      their tobacco training needs. The purpose of this study was to assess the tobacco
      intervention practices and training needs of Hispanic physicians. METHODS: Data
      was collected through a validated survey instrument among a cross-sectional
      sample of self-reported Hispanic physicians. Data analyses included frequencies,
      descriptive statistics, and factorial analyses of variance. RESULTS: The response
      rate was 55.5%. The majority of respondents (73.3%) were middle-age males. Less
      than half of respondents routinely performed the most basic intervention: asking
      patients about smoking status (44.4%) and advising smoking patients to quit
      (42.2%). Twenty-five percent assisted smoking patients by talking to them about
      the health risks of smoking, providing education materials or referring them to
      cessation programs. Only 4.4% routinely arranged follow-up visits or phone calls
      for smoking patients. The majority of respondents (64.4%) indicated that they
      prescribe cessation treatments to less than 20% of smoking patients. A few (4.4%)
      routinely used behavioral change techniques or programs. A minority (15.6%)
      indicated that they routinely ask their patients about exposure to tobacco smoke,
      and 6.7% assisted patients exposed to secondhand smoke in understanding the
      health risks associated with environmental tobacco smoke (ETS). The most
      frequently encountered barriers preventing respondents from intervening with
      patients who smoke included: time, lack of training, lack of receptivity by
      patients, and lack of reimbursement by third party payers. There was no
      significant main effect of type of physician, nor was there an interaction effect
      (gender by type of physician), on tobacco-related practices. CONCLUSION: The
      results indicate that Hispanic physicians, similarly to U.S. physicians in
      general, do not meet the level of intervention recommended by health care
      agencies. The results presented will assist in the development of tobacco
      training initiatives for Hispanic physicians.

PMID- 16287501
TI  - Aberrant E-cadherin staining patterns in invasive mammary carcinoma.
AB  - BACKGROUND: E-cadherin, a cell surface protein involved in cell adhesion, is
      present in normal breast epithelium, benign breast lesions, and in breast
      carcinoma. Alterations in the gene CDH1 on chromosome 16q22 are associated with
      changes in E-cadherin protein expression and function. Inactivation of E-cadherin
      in lobular carcinomas and certain diffuse gastric carcinomas may play a role in
      the dispersed, discohesive "single cell" growth patterns seen in these tumors.
      The molecular "signature" of mammary lobular carcinomas is the loss of E-cadherin
      protein expression as evidenced by immunohistochemistry, whereas ductal
      carcinomas are typically E-cadherin positive. PATIENTS AND METHODS: We report on
      E-cadherin immunostaining patterns in five cases of invasive mammary carcinoma.
      RESULTS: These were five exceptional instances in which the E-cadherin
      immunophenotype did not correspond to the apparent histologic classification of
      the lesion. These cases which are exceedingly rare in our experience are the
      subject of this report. CONCLUSION: Findings such as those illustrated in this
      study occur in virtually all biologic phenomena and they do not invalidate the
      very high degree of correlation between the expression of E-cadherin and the
      classification of breast carcinomas as ductal or lobular type on the basis of
      conventional histologic criteria.

PMID- 16287502
TI  - Fine needle aspiration diagnosis of extracranial glioblastoma multiforme: Case
      report and review of the literature.
AB  - BACKGROUND: Hitherto uncommon, the incidence of extracranial metastases of
      primary brain malignancies may increase, with improved treatment methods and
      longer patient survival. Fine needle aspiration biopsy is a simple, safe and
      reliable method to diagnose metastatic malignancy. It has definite advantages
      over tissue biopsy, which is more invasive and is of higher risk to the patient.
      Ours is a case of glioblastoma multiforme, which metastasized to the scalp and
      was diagnosed on fine needle aspiration biopsy. Only a few articles document the
      cytological features of extracranial glioblastoma multiforme, diagnosed by fine
      needle aspiration biopsy. CASE PRESENTATION: We report the case of an elderly
      female who presented with focal neurological symptoms. She was diagnosed
      radiologically with an intracranial lesion in the left temporal region, which was
      subsequently resected. Histology revealed a glioblastoma multiforme confirmed by
      immunohistochemistry. The tumor recurred subsequently and the patient was treated
      with chemotherapy, intraoperatively. At a later stage, she presented with a scalp
      mass on which fine needle aspiration biopsy was performed. The cytomorphological
      features aided by immunohistochemistry supported a diagnosis of metastatic
      glioblastoma multiforme. The mass was later resected and histology confirmed the
      fine needle aspiration diagnosis of glioblastoma multiforme. CONCLUSION: Reports
      of extracranial metastases of primary brain tumors are few. When they do occur,
      the primary cause is implantation during surgery or biopsy. However, spontaneous
      metastases to other organs do occur rarely. We believe fine needle aspiration
      biopsy to be very useful in the diagnosis of metastatic glioblastoma multiforme.
      The ability to use a cellblock for immunohistochemical studies is greatly
      advantageous and helpful in differentiating this tumor, from other malignancies
      that can occur in the scalp. A detailed discussion of the material obtained from
      fine needle aspiration biopsy of metastatic glioblastoma multiforme is presented,
      as well as a review of previous accounts in the literature.

PMID- 16287503
TI  - Granulocyte heterochromatin: defining the epigenome.
AB  - BACKGROUND: Mammalian blood neutrophilic granulocytes are terminally
      differentiated cells, possessing extensive heterochromatin and lobulated (or ring
      shaped) nuclei. Despite the extensive amount of heterochromatin, neutrophils are
      capable of increased gene expression, when activated by bacterial infection.
      Understanding the mechanisms of transcriptional repression and activation in
      neutrophils requires detailing the chromatin epigenetic markers, which are
      virtually undescribed in this cell type. Much is known about the heterochromatin
      epigenetic markers in other cell-types, permitting a basis for comparison with
      those of mature normal neutrophilic granulocytes. RESULTS: Immunostaining and
      immunoblotting procedures were employed to study the presence of repressive
      histone modifications and HP1 proteins in normal human and mouse blood
      neutrophils, and in vitro differentiated granulocytes of the mouse promyelocytic
      (MPRO) system. A variety of repressive histone methylation markers were
      detectable in these granulocytes (di- and trimethylated H3K9; mono-, di- and
      trimethyl H3K27; di- and trimethyl H4K20). However, a paucity of HP1 proteins was
      noted. These granulocytes revealed negligible amounts of HP1 alpha and beta, but
      exhibited detectable levels of HP1 gamma. Of particular interest, mouse blood and
      MPRO undifferentiated cells and granulocytes revealed clear co-localization of
      trimethylated H3K9, trimethylated H4K20 and HP1 gamma with pericentric
      heterochromatin. CONCLUSION: Mature blood neutrophils possess some epigenetic
      heterochromatin features that resemble those of well-studied cells, such as
      lymphocytes. However, the apparent paucity of HP1 proteins in neutrophils
      suggests that heterochromatin organization and binding to the nuclear envelope
      may differ in this cell-type. Future investigations should follow changes in
      epigenetic markers and levels of HP1 proteins during granulopoiesis and bacterial
      activation of neutrophils.

PMID- 16287504
TI  - EEG correlates of verbal and nonverbal working memory.
AB  - BACKGROUND: Distinct cognitive processes support verbal and nonverbal working
      memory, with verbal memory depending specifically on the subvocal rehearsal of
      items. METHODS: We recorded scalp EEG while subjects performed a Sternberg task.
      In each trial, subjects judged whether a probe item was one of the three items in
      a study list. Lists were composed of stimuli from one of five pools whose items
      either were verbally rehearsable (letters, words, pictures of common objects) or
      resistant to verbal rehearsal (sinusoidal grating patterns, single dot
      locations). RESULTS: We found oscillatory correlates unique to verbal stimuli in
      the theta (4-8 Hz), alpha (9-12 Hz), beta (14-28 Hz), and gamma (30-50 Hz)
      frequency bands. Verbal stimuli generally elicited greater power than did
      nonverbal stimuli. Enhanced verbal power was found bilaterally in the theta band,
      over frontal and occipital areas in the alpha and beta bands, and centrally in
      the gamma band. When we looked specifically for cases where oscillatory power in
      the time interval between item presentations was greater than oscillatory power
      during item presentation, we found enhanced beta activity in the frontal and
      occipital regions. CONCLUSION: These results implicate stimulus-induced
      oscillatory activity in verbal working memory and beta activity in the process of
      subvocal rehearsal.

PMID- 16287505
TI  - Fibrinogen storage disease without hypofibrinogenemia associated with estrogen
      therapy.
AB  - BACKGROUND: Cytoplasmic inclusion bodies within hepatocytes may have different
      etiologies, including the Endoplasmic Reticulum Storage Diseases (ERSDs). ERSD is
      a pathological condition characterized by abnormal accumulation of proteins
      destined for secretion in the endoplasmic reticulum of hepatocytes; it may be
      congenital (primary) or acquired (secondary). Fibrinogen storage disease is a
      form of ERSD. CASE PRESENTATION: We present a case of fibrinogen storage disease
      secondary to estrogen replacement therapy. Its causal relationship to the drug is
      shown by histological, immunohistochemical and ultrastructural studies of paired
      liver biopsies obtained during and after the drug therapy. CONCLUSION: The liver
      biopsies of patients with idiopathic liver enzyme abnormalities should be
      carefully evaluated for cytoplasmic inclusion bodies and, although rare,
      fibrinogen deposits.

PMID- 16287507
TI  - Long-term disease-free survival in advanced melanomas treated with nitrosoureas:
      mechanisms and new perspectives.
AB  - BACKGROUND: Median survival of metastatic malignant melanoma is 6.0 to 7.5
      months, with a 5-year survival of approximately 6.0%. Although long-term complete
      remissions are rare, few reports describe cases after chemotherapy. Fifty-three
      patients with metastatic melanoma were treated with Cystemustine, a chloroethyl
      nitrosourea (CENU) (60 or 90 mg/m2). CASE PRESENTATION: We describe 5 cases,
      presenting with complete response with long-term disease-free survival of long
      term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone.
      CONCLUSION: Long-term survival has already been described in literature, but in
      all cases they have been obtained after chemotherapy associated with or followed
      by surgery. But despite these noteworthy and encouraging but also rare results,
      it appears essential to increase Cystemustine efficiency.

PMID- 16287506
TI  - Short report: Autistic gastrointestinal and eating symptoms treated with
      secretin: a subtype of autism.
AB  - Pervasive Developmental Disorders (PDD) are chronic, lifelong disorders for which
      there is as yet no effective cure, and medical management remains a challenge for
      clinicians. The current report describes two patients affected by autistic
      disorder with associated gastrointestinal symptoms. They received multiple doses
      of intravenous secretin for a six-month period and were assessed with several
      specific outcome measures to evaluate drug effect. The administration of secretin
      led to some significant and lasting improvement in only one case.
      Gastroesophageal reflux may contribute to some of the behavioural problems and
      explain the effect of secretin since its suppressive effect on gastric secretion
      is well known. It is also true that autistic children with gastroesophageal
      reflux and a higher IQ could constitute a subtype which responds to secretin
      administration and that could be labelled as a "gastrointestinal subtype".

PMID- 16287508
TI  - Targeted oligonucleotide-mediated microsatellite identification (TOMMI) from
      large-insert library clones.
AB  - BACKGROUND: In the last few years, microsatellites have become the most popular
      molecular marker system and have intensively been applied in genome mapping,
      biodiversity and phylogeny studies of livestock. Compared to single nucleotide
      polymorphism (SNP) as another popular marker system, microsatellites reveal
      obvious advantages. They are multi-allelic, possibly more polymorphic and cheaper
      to genotype. Calculations showed that a multi-allelic marker system always has
      more power to detect Linkage Disequilibrium (LD) than does a di-allelic marker
      system. Traditional isolation methods using partial genomic libraries are time
      consuming and cost-intensive. In order to directly generate microsatellites from
      large-insert libraries a sequencing approach with repeat-containing
      oligonucleotides is introduced. RESULTS: Seventeen porcine microsatellite markers
      were isolated from eleven PAC clones by targeted oligonucleotide-mediated
      microsatellite identification (TOMMI), an improved efficient and rapid flanking
      sequence-based approach for the isolation of STS-markers. With the application of
      TOMMI, an average of 1.55 (CA/GT) microsatellites per PAC clone was identified.
      The number of alleles, allele size distribution, polymorphism information content
      (PIC), average heterozygosity (HT), and effective allele number (NE) for the STS
      markers were calculated using a sampling of 336 unrelated animals representing
      fifteen pig breeds (nine European and six Chinese breeds). Sixteen of the
      microsatellite markers proved to be polymorphic (2 to 22 alleles) in this
      heterogeneous sampling. Most of the publicly available (porcine) microsatellite
      amplicons range from approximately 80 bp to 200 bp. Here, we attempted to utilize
      as much sequence information as possible to develop STS-markers with larger
      amplicons. Indeed, fourteen of the seventeen STS-marker amplicons have minimal
      allele sizes of at least 200 bp. Thus, most of the generated STS-markers can
      easily be integrated into multilocus assays covering a broader separation
      spectrum. Linkage mapping results of the markers indicate their potential
      immediate use in QTL studies to further dissect trait associated chromosomal
      regions. CONCLUSION: The sequencing strategy described in this study provides a
      targeted, inexpensive and fast method to develop microsatellites from large
      insert libraries. It is well suited to generate polymorphic markers for selected
      chromosomal regions, contigs of overlapping clones and yields sufficient high
      quality sequence data to develop amplicons greater than 250 bases.

PMID- 16287509
TI  - Characterization of lymphocyte populations in nonspecific interstitial pneumonia.
AB  - STUDY OBJECTIVES: Nonspecific interstitial pneumonia (NSIP) has been identified
      as a distinct entity with a more favorable prognosis and better response to
      immunosuppressive therapies than usual interstitial pneumonia (UIP). However the
      inflammatory profile of NSIP has not been characterized. DESIGN: Using
      immunohistochemistry techniques on open lung biopsy specimens, the infiltrate in
      NSIP was characterized in terms of T and B cells, and macrophages, and the T cell
      population further identified as either CD4 (helper) or CD8 (suppressor
      cytotoxic) T cells. The extent of Th1 and Th2 cytokine producing cells was
      determined and compared to specimens from patients with UIP. RESULTS: In ten NSIP
      tissue samples 41.4 +/- 4% of mononuclear cells expressed CD3, 24.7 +/- 1.8% CD4,
      19.1 +/- 2% CD8, 27.4 +/- 3.9% CD20, and 14.3 +/- 1.6% had CD68 expression.
      Mononuclear cells expressed INFgamma 21.9 +/- 1.9% of the time and IL-4 in 3.0 +/
      1%. In contrast, biopsies from eight patients with UIP demonstrated
      substantially less cellular staining for either cytokine (INFgamma; 4.6 +/- 1.7%
      and IL-4; 0.6 +/- 0.3%). Significant populations of CD20 positive B-cells were
      also identified. CONCLUSION: The lymphocytic infiltrate in NSIP is characterized
      by an elevated CD4/CD8 T-cell ratio, and is predominantly of Th1 type, with
      additional populations rich in B-cells. Such features are consistent with the
      favorable clinical course observed in patients with NSIP compared to UIP.

PMID- 16287510
TI  - Blue-native PAGE in plants: a tool in analysis of protein-protein interactions.
AB  - Intact protein complexes can be separated by apparent molecular mass using a
      standard polyacrylamide gel electrophoresis system combining mild detergents and
      the dye Coomassie Blue. Referring to the blue coloured gel and the gentle method
      of solubilization yielding native and enzymatically active protein complexes,
      this technique has been named Blue-Native Polyacrylamide Gel-Electrophoresis (BN
      PAGE). BN-PAGE has become the method of choice for the investigation of the
      respiratory protein complexes of the electron transfer chains of a range of
      organisms, including bacteria, yeasts, animals and plants. It allows the
      separation in two dimensions of extremely hydrophobic protein sets for analysis
      and also provides information on their native interactions. In this review we
      discuss the capabilities of BN-PAGE in proteomics and the wider investigation of
      protein:protein interactions with a focus on its use and potential in plant
      science.

PMID- 16287515
TI  - [Obsessive-compulsive disorder in children. Psychopathology and comorbidity].

PMID- 16287511
TI  - Cytokine responses during chronic denervation.
AB  - BACKGROUND: The aim of the present study was to examine inflammatory responses
      during Wallerian degeneration in rat peripheral nerve when the regrowth of axons
      was prevented by suturing. METHODS: Transected rat sciatic nerve was sutured and
      ligated to prevent reinnervation. The samples were collected from the left
      sciatic nerve distally and proximally from the point of transection. The
      endoneurium was separated from the surrounding epi- and perineurium to examine
      the expression of cytokines in both of these compartments. Macrophage invasion
      into endoneurium was investigated and Schwann cell proliferation was followed as
      well as the expression of cytokines IL-1beta, IL-10, IFN-gamma and TNF-alpha
      mRNA. The samples were collected from 1 day up to 5 weeks after the primary
      operation. RESULTS: At days 1 to 3 after injury in the epi-/perineurium of the
      proximal and distal stump, a marked expression of the pro-inflammatory cytokines
      TNF-alpha and IL-1beta and of the anti-inflammatory cytokine IL-10 was observed.
      Concurrently, numerous macrophages started to gather into the epineurium of both
      proximal and distal stumps. At day 7 the number of macrophages decreased in the
      perineurium and increased markedly in the endoneurium of both stumps. At this
      time point marked expression of TNF-alpha and IFN-gamma mRNA was observed in the
      endo- and epi-/perineurium of the proximal stump. At day 14 a marked increase in
      the expression of IL-1beta could be noted in the proximal stump epi-/perineurium
      and in the distal stump endoneurium. At that time point many macrophages were
      observed in the longitudinally sectioned epineurium of the proximal 2 area as
      well as in the cross-section slides from the distal stump. At day 35 TNF-alpha,
      IL-1beta and IL-10 mRNA appeared abundantly in the proximal epi-/perineurium
      together with macrophages. CONCLUSION: The present studies show that even during
      chronic denervation there is a cyclic expression pattern for the studied
      cytokines. Contrary to the previous findings on reinnervating nerves the studied
      cytokines show increased expression up to 35 days. The high expressions of pro
      inflammatory and anti-inflammatory cytokines in the proximal epi-/perineurial
      area at day 35 may be involved in the formation of fibrosis due to irreversible
      nerve injury and thus may have relevance to the formation of traumatic neuroma.

PMID- 16287516
TI  - [When thoughts become compulsions. Obsessive-compulsive disorder in children].
AB  - OCD (obsessive-compulsive disorder) is characterised by the presence of annoying,
      unwelcome and intrusive obsessions and compulsions. The obsessions appear over
      and over and the child recognize them as something strange and unwelcome, but at
      the same time they are clearly a product of his/her own mind and not a
      hallucination or a thought disorder as seen in psychotic disturbances.
      Compulsions are imposed actions that the child feels it has to perform, often in
      a certain pattern. Both children and adults can suffer from OCD. Almost 2/3 of
      adults with OCD report onset of their OCD symptoms in childhood or early
      adolescence. Previously, OCD among children and adolescents was considered to be
      rare, but newer epidemiologic surveys show that 1-1% of children and adolescents
      suffer from OCD in such a degree that they fulfil the diagnostic criteria. The
      prevalence varies surprisingly little in various countries regardless of cultural
      background.

PMID- 16287512
TI  - Evaluation and selection of tandem repeat loci for Streptococcus pneumoniae MLVA
      strain typing.
AB  - BACKGROUND: Precise identification of bacterial pathogens at the strain level is
      essential for epidemiological purposes. In Streptococcus pneumoniae, the
      existence of 90 different serotypes makes the typing particularly difficult and
      requires the use of highly informative tools. Available methods are relatively
      expensive and cannot be used for large-scale or routine typing of any new
      isolate. We explore here the potential of MLVA (Multiple Loci VNTR Analysis;
      VNTR, Variable Number of Tandem Repeats), a method of growing importance in the
      field of molecular epidemiology, for genotyping of Streptococcus pneumoniae.
      RESULTS: Available genome sequences were searched for polymorphic tandem repeats.
      The loci identified were typed across a collection of 56 diverse isolates and
      including a group of serotype 1 isolates from Africa. Eventually a set of 16
      VNTRs was proposed for MLVA-typing of S. pneumoniae. These robust markers were
      sufficient to discriminate 49 genotypes and to aggregate strains on the basis of
      the serotype and geographical origin, although some exceptions were found. Such
      exceptions may reflect serotype switching or horizontal transfer of genetic
      material. CONCLUSION: We describe a simple PCR-based MLVA genotyping scheme for
      S. pneumoniae which may prove to be a powerful complement to existing tools for
      epidemiological studies. Using this technique we uncovered a clonal population of
      strains, responsible for infections in Burkina Faso. We believe that the proposed
      MLVA typing scheme can become a standard for epidemiological studies of S.
      pneumoniae.

PMID- 16287517
TI  - [Psychosocial factors at work and ischemic heart disease].
AB  - We reviewed the epidemiologic research on the relationship between psychosocial
      factors at work and ischemic heart disease (IHD). A literature search identified
      35 longitudinal English-language studies published in peer-reviewed journals.
      Nine out of 18 cohort studies and 14 out of 17 case control studies showed a
      significant association between psychosocial factors at work and IHD. In three of
      the studies, the results showed the expected association without it being
      significant, and in nine of the studies no association was found. Twenty-nine of
      the studies achieved a satisfactory quality score of at least 16 points out of a
      possible 25. Among these, 19 found a positive association between psychosocial
      factors at work and IHD. Nineteen of the studies had used the job strain model
      suggested by Karasek and Theorell as the model of exposure. Eleven of these found
      a clear association between job strain and IHD, three found a partial
      association, and five showed negative results. Three of the negative studies had
      used the ecological method as the measure of exposure. None of the five American
      studies found any association between job strain and IHD. The 11 positive studies
      were carried out in the UK, Sweden, the Czech Republic, and Denmark. An imbalance
      between efforts rendered and rewards, as well as long working hours, was also
      found to increase the risk of IHD in the six studies which had looked into these
      exposures. The results of this literature review ought to have consequences for
      the prevention of IHD and affect the advice offered to IHD patients.

PMID- 16287518
TI  - [Organ transplants for HIV-infected patients--time for reevaluation?].
AB  - With the improvement in antiretroviral therapy, comorbidity is increasingly a
      cause of morbidity among HIV-infected patients. In the United States and several
      European countries, kidney and liver transplantations have been performed on
      selected HIV-infected patients. The short-term results have been comparable to
      those among HIV-negative recipients. Based on these results, it is recommended
      that kidney and liver transplants be offered to Danish HIV patients based on the
      same criteria as those that apply for non-HIV-infected patients with end-stage
      kidney or liver disease.

PMID- 16287519
TI  - [Hepatic failure due to nevirapine treatment for HIV infection].
AB  - Two cases of hepatic failure due to nevirapine treatment are reported. One
      patient erroneously took double dosing of nevirapine, while the other patient did
      not attend the scheduled laboratory control two weeks after the initiation of
      nevirapine treatment. In spite of maximal conservative treatment, this patient
      died five days after admission. These cases emphasise the importance of giving
      patients thorough instructions as well as doing clinical and laboratory
      monitoring of patients receiving highly active antiretroviral treatment (HAART).

PMID- 16287520
TI  - [Diagnostic laparoscopy under local anaesthesia].
AB  - Laparoscopy under local anaesthesia (LULA) is a safe, feasible and well-tolerated
      procedure. LULA has been successfully used for such outpatient gynaecological
      procedures as diagnosis of chronic pelvic pain and sterilisation. Single studies
      have indicated that LULA can be performed for diagnosis of possible intra
      abdominal catastrophe in ICU patients, appendectomy and preperitoneal inguinal
      hernia repair. LULA in abdominal surgery for diagnosis of conditions presenting
      with acute lower abdominal pain is being introduced at our institution. This
      paper describes the possible applications of LULA in current practice as well as
      the technical aspects of the procedure.

PMID- 16287521
TI  - [New research councils in Denmark and the European Union].
AB  - Research is on the political agenda in Denmark and the other EU countries. In
      January 2004, a new structure for the Danish Research Council was launched,
      including the Danish Councils for Independent Research and the the Danish Council
      for Strategic Research. The Danish Political Research Council gives independent
      advice to the government and the Parliament. ESFRI, the European Strategy Forum
      on Research Infrastructure, is an organisation giving advice to the European
      Union on questions of research infrastructure. Also in Denmark, a research
      infrastructure programme has been initiated. For researchers it is important to
      be informed about the research council structures in order to be able to secure
      optimal research funding.

PMID- 16287522
TI  - [Survival rate after radical hysterectomy for cervical cancer performed in a
      central hospital].
AB  - INTRODUCTION: No recent Danish data exist on survival rate by stage for cervical
      cancer. Further centralization of cancer treatment is presently being discussed,
      and this report aims to discuss and broaden the view on the issues of survival,
      centralization and quality of treatment. MATERIALS AND METHODS: During the period
      1982-2002, 123 women were diagnosed with cervical cancer and operated on by two
      gynaecologists in a central hospital in Denmark, using a modification of
      Okabayashi's operation. Stage 1b cancer was found in 111 women. The hospital
      charts were reviewed retrospectively, and data on survival rates were drawn from
      hospital records and registers. RESULTS: The occurrence of lymph gland metastasis
      was associated with the stage of the cancer. Relapse of tumor occurred in 29
      women, with 21 women subsequently succumbing to the disease. No difference was
      found in survival rate in stage 1 according to treatment of relapse. The five-
      and ten-year survival rates in stage 1b were 87% and 82%, respectively.
      DISCUSSION: Similarly to what has been shown by other studies, the mortality rate
      was not affected by the decentralized setting and care. The small number of
      surgeons involved ensured homogeneity of and consistency in operative treatment
      despite the changes in perioperative care over the 20-year period.

PMID- 16287523
TI  - [Barriers in screening for cervical cancer].
AB  - INTRODUCTION: Approximately 25 percent of Danish women do not participate in the
      national cervical cancer screening programme. This study aims to identify and
      describe the barriers to participation. MATERIALS AND METHODS: Eight focus groups
      were held with 48 women aged 23-39. RESULTS: There is usually more than one
      reason for an individual woman's non-participation. The various barriers are
      often mutually reinforced. The study reveals seven general barriers: Insufficient
      and incorrect knowledge about screening and cervical cancer, Lack of
      understanding of why screening is relevant to the individual woman, The
      gynaecological examination, Fear of having cancer, Attitude towards seeing one's
      general practitioner, Practical circumstances that make participation difficult,
      Attitude towards screening. In general, women do not discuss cervical cancer
      screening with people close to them, but general practitioners seem to have a
      great potential to help them overcome the barriers. DISCUSSION: This study
      indicates that non-participation does not necessarily mean that the individual
      woman has made an informed choice. But since the individual woman often has more
      than one barrier towards screening, it is not an issue of information and
      knowledge alone. In order to increase compliance, efforts must be made to resolve
      as many of the seven barriers as possible.

PMID- 16287524
TI  - [Patient-experienced quality assessed in two national surveys].
AB  - INTRODUCTION: Surveys of patients' experiences can be used for other purposes
      than to disclose patients' overall satisfaction. They can, for example, also be
      used to select focus areas in the health care sector. In this article two large
      national surveys of patient-experienced quality are compared. The advantages and
      disadvantages of the applied methods and various applications of the surveys are
      discussed. MATERIALS AND METHODS: The Danish National Patient Satisfaction Survey
      was based on a questionnaire with questions about patients' experiences. The
      questionnaires were sent to the patients after discharge. All 62 public Danish
      hospitals were included. The Patient Reports Survey was based on a questionnaire
      with questions about whether the patient had received certain services. The
      questionnaire was given to each patient on the day of discharge and returned
      before the patient left the hospital. All medical wards were invited to
      participate in the survey. RESULTS: Despite differences in questions, design and
      methods, the two surveys showed agreement in the areas where patients experienced
      flaws in the quality of services. CONCLUSION: In future surveys the advantages
      and disadvantages of data feedback, inclusion on the basis of data registers,
      sample sizes and the possibility of being supplied with ward-specific data should
      be taken into consideration. The advantages and disadvantages of involving
      employees should be counterbalanced in each survey. The Danish National Patient
      Satisfaction Survey is suitable for external evaluation and benchmarking between
      hospitals, while the applied methods in the Patient Reports Survey are best
      suited to internal self-evaluation and quality improvement within hospital
      departments.

PMID- 16287525
TI  - [Two cases of multilocular cystic nephroma, a rare benign tumor of the kidney].
AB  - We present two case reports of multilocular cystic nephroma (MCN). MCN is a rare
      benign tumor of the kidney that is difficult to differentiate from malignant
      tumor by diagnostic imaging (ultrasound, CT) and cytology on fine-needle
      aspiration. This is why most cases end up with nephrectomy and diagnosis is based
      on the histopathological findings. In one of our two cases, a nephrectomy was
      performed, and in the other the tumor was resected from the kidney. The origin of
      MCN is uncertain, and only about 200 cases have been reported in the literature.

PMID- 16287530
TI  - [Placebo against migraine as effective as acupuncture].

PMID- 16287527
TI  - [Gastroenterologic endoscopy is primarily a task for physicians!].

PMID- 16287541
TI  - Ga2Len: coordinated research.

PMID- 16287542
TI  - IL6, IL10 and TGFB1 gene polymorphisms in coeliac disease: differences between
      DQ2 positive and negative patients.
AB  - Predisposition to coeliac disease (CD) might be partially due to an individual
      pattern of hyper-inflammatory biased immune response. One of these patterns of
      intense response may be linked to the haplotype carrying HLA-DQ2 alleles and TNF 
      308A allele. However, 10 % of CD patients do not express the DQ2 heterodimer and
      these do not usually carry the TNF -308A allele. A similar response might be
      achieved by genes codifying other cytokines. OBJECTIVES: To study biallelic
      polymorphisms in genes codifying for TNFalpha, IL10, IL6 and TGFbeta1 in DQ2
      negative CD patients and to compare the results with DQ2 positive patients and
      healthy controls, in order to establish whether any of these polymorphisms have a
      role in CD susceptibility. METHODS: TNF -308 (G > A), IL-6 -174 (G > C) and TGFB1
      codon 10 (+ 869, T > C) and codon 25 (+ 915, G > C) polymorphisms and IL-10
      haplotype of polymorphisms in positions -1082 (G > A), -819 (C > T) and -592 (C >
      A) were typed by a SSP-PCR technique. RESULTS: The distribution of allele
      frequencies for TNF -308 is different between DQ2 positive CD patients and
      controls and the same occurs for haplotype frequencies of the IL10 promoter (
      1082, -819, -592): The frequencies of the TNF -308A allele (p = 0.027), TNF -308A
      carriers (p = 0.031) and of IL10GCC haplotype are increased (p = 0.013) in DQ2
      positive CD patients. However, the IL6 -174 allele G is more frequent in DQ2
      negative patients than in healthy controls (p = 0.018), DQ2 negative controls (p
      = 0,018), and DQ2 positive patients (p = 0.008). CONCLUSIONS: DQ2 negative CD
      patients show an increased frequency of genotypes associated to IL6 high
      production. These were mainly allele G homozygous for the IL6 gene (-174)
      polymorphism. The IL6 -174GG genotype (homozygous) may be an additional risk
      marker for CD in DQ2 negative patients, representing an alternative
      susceptibility factor for CD when TNF -308A is negative.

PMID- 16287543
TI  - Immunologic and clinical responses to parenteral immunotherapy in peanut
      anaphylaxis--a study using IgE and IgG4 immunoblot monitoring.
AB  - BACKGROUND: Specific desensitisation to food allergens, which produce anaphylaxis
      after ingestion, has not been considered as a treatment for food allergy until
      recently. The purpose of this study was to assess if a parenteral immunotherapy
      program, using a partially characterised crude peanut extract, could induce a
      state of immunological tolerance in a patient who exhibited anaphylaxis, asthma
      and urticaria on exposure to peanut and other legumes. A further aim was to
      measure the serum antibody responses to the immunotherapy. METHODS AND RESULTS:
      We report the successful desensitisation towards all of the legumes tested of a
      male patient on parenteral immunotherapy using a partially characterised peanut
      extract. The immunologic parameters measured during treatment included specific
      IgE and IgG4 for peanut, soybean, pea and lentil extracts. Immunoblots of
      specific IgE and IgG4 were made before and after therapy. The antibody response
      followed the same pattern seen in successful desensitisation of patients with bee
      venom anaphylaxis. The IgG4 levels increased strongly from a low pre-treatment
      level in proportion to the antigen dose received. The antigen-specific IgE levels
      gradually fell from a high pretreatment level, but remained significantly
      elevated. Immunoblotting for specific IgE and IgG4 demonstrated that acquisition
      of clinical tolerance after therapy was associated with declines in the number
      and intensity of bands in IgE blots and the development of more bands of
      increasing density in the IgG4 blots. CONCLUSIONS: Parenteral immunotherapy may
      offer an alternative treatment to lifelong dietary restriction and epinephrine
      injections in patients who exhibit life-threatening IgE-mediated anaphylaxis to
      peanut. Cross desensitisation to other legumes appears to have occurred in this
      study. The quality and potency of the extract used is an important factor in
      achieving the desired acquisition of clinical tolerance. In our patient this
      tolerance correlated with his ability to maintain high levels of specific IgG4,
      which acted as a marker of protection against anaphylaxis. The use of IgG4
      immunoblotting may provide an improved level of discrimination in the assessment
      of correlation of clinical efficacy with the immunologic response.

PMID- 16287544
TI  - Wheezing during the first year of life in infants from low-income population: a
      descriptive study.
AB  - BACKGROUND: Recurrent wheezing (RW) plays an important role in the morbidity and
      mortality of children during the first year of life in developing regions and its
      actual incidence in those areas is virtually unknown. METHODS AND RESULTS: This
      study describes the occurrence of wheezing during the first year of life in a
      birth cohort of 188 infants followed monthly and living in a poor urban area in
      Santiago de Chile. This study showed that 80.3 % of the infants in the cohort had
      one or more wheezing episode during the first year of life, 43.1 % had RW (3 or
      more wheezing episodes), 44.1 % had their first wheezing within the first three
      months of life and 13.3 % had pneumonia (PN). Having one or more episode of
      wheezing in the first three months of life was the main risk factor for suffering
      from RW during the first year and RW was a significant risk factor for having PN.
      CONCLUSIONS: This study found a high prevalence of RW in infants from a low
      income population during the first year of life with the disease starting very
      early in their lives, progressing with more frequent episodes and being
      significantly associated to PN, particularly in the first 6 months of life.

PMID- 16287545
TI  - Clinical and patient based evaluation of immunotherapy for grass pollen and mite
      allergy.
AB  - BACKGROUND: Treatment of allergic disease can be done by pharmacological
      intervention by allergen avoidance--in the following called standard care (SC),
      or by specific treatment with allergy vaccination; Specific Immunotherapy (SIT).
      The aim of this study were to evaluate the effects of subcutaneously
      administrated SIT compared to SC by objective (clinical/medical records) and
      subjective parameters (patient's opinion) in a before/after SIT study. METHODS:
      The study included retrospectively all grass- and mite allergic 16-60 year old
      patients (N = 253) who had started SIT for grass pollen or mite allergy during
      the period 1.1.1996-1.1.2002 at The Allergy Unit, Aarhus University Hospital, or
      at a specialist practice in Aarhus. Relevant data were collected before/after
      treatment from medical records and from a specific designed questionnaire. The
      following indicators for effect were applied: Success of immunotherapy expressed
      as completion of up dosing phase, change in symptoms, a comparison of overall
      rhinoconjunctivitis symptoms, number of symptom free days per year, effect of
      pharmaceuticals, change in physical and psychological wellbeing and number of
      lost days from work/education and leisure activities. RESULTS: Compliance for
      completed up dosing for SIT was 94 % (95 % CI 90-97). The questionnaire revealed
      that after SIT there were a significant reduction in degree of symptoms, 84 % (95
      % CI 79-89) of the respondents achieved a reduction in over all
      rhinoconjunctivitis score, there were an increase in symptom free days per year,
      a decrease in days off/incapacity from work/education and leisure activities, an
      improved effect of the pharmaceuticals used for allergic symptoms and an
      improvement in physical and psychological wellbeing. The study also showed that
      SIT was more effective treating rhinoconjunctivitis symptoms than lung symptoms.
      CONCLUSION: The study revealed great advantages of SIT compared to SC and a high
      compliance for SIT during the up dosing period.

PMID- 16287546
TI  - Asthma-like symptoms prevalence in five Turkish urban centers.
AB  - BACKGROUND: Asthma, which is a chronic inflammatory disorder of the airways
      characterized by the infiltration of inflammatory cells, is a common cause of
      morbidity in adults. It is almost the third leading cause of preventable
      hospitalization in the developed countries and accounts for approximately
      millions of visits to emergency departments. METHODS: In this study, we aimed to
      determine asthma prevalence in five urban centers in Turkey. Three of the cities
      were located in the middle-west region of the Anatolia one of them as located
      across the Mediterranean cost and the last one was in the north part of the
      country. Data of totally 2353 participants was collected by the trained
      interviewers, who visited the households and administered the questionnaire to
      the household members at or over the age of 15 years. RESULTS: The prevalence of
      asthma was found to be 6.6 % and the difference of asthma prevalence between the
      urban centers was statistically non-significant (p = 0.059).

PMID- 16287547
TI  - Sensitization increases esterase-positive macrophage number in appendix from an
      animal model of food allergy.
AB  - BACKGROUND: Macrophages are mononuclear cells with phagocytic and antigen
      presenting properties. The role of macrophages in IgE-dependent allergic
      reactions and oral tolerance remains unclear. In previous works we demonstrated
      that ovalbumin (OVA)-sensitized rabbits present histopathological modifications
      of the mucosa in different regions of the digestive tract. The present study
      analyzes macrophage distribution and quantitative modifications in the cecal
      appendix of OVA-sensitized animals. METHODS: Adult new Zealand rabbits were
      divided into two groups: G1 (non-sensitized normal controls) and G2 (rabbits
      sensitized to OVA twice by subcutaneous route, with aluminum hydroxide as
      adjuvant). The alpha-naphthyl esterase technique was used for macrophage
      detection. RESULTS: Specific anti-OVA IgE was detected in sensitized animals by
      the PCA (passive cutaneous anaphylaxis) method. In 5 regions of the cecal
      appendix we observed a significant increase in the number of macrophages in
      sensitized animals (G2) versus the control group (G1). The observed sensitization
      mediated increase in cells is probably related to enhanced recruitment of
      monocytes from peripheral blood towards the appendix. This process could be
      induced by chemical mediators, and demonstrates macrophage participation in local
      immune response during sensitization phenomena.

PMID- 16287548
TI  - Flare up to betalactams.
AB  - BACKGROUND: The flare up phenomenon has most frequently been described with
      nickel. Not many cases of flare up to drugs have reported in the literature,
      however we have reported it with different medications. METHODS AND RESULTS: A 31
      year-old woman developed an adverse reaction with an antibiotic during her
      childhood. Prick test with penicillin (100,000 IU/ml), penicilloyl polylysine
      (PPL), minor determinant mixture (MDM), amoxicillin (200 mg/ml), ampicillin (200
      mg/ml) and cephalotin (200 mg/ml), and intradermal test to the same substances
      diluted in saline were all negative immediately. We performed an oral challenge
      test with 500 mg of amoxicillin. Twelve hours later, the intradermal test to PPL
      and MDM became positive (PPL 10 x 10 mm, MDM 8 x 7 mm). All patch tests were
      positive after 72 hours with erythema, vesicles and infiltration and the patient
      also had exanthema with pruritus on her entire body. CONCLUSIONS: We present one
      patient with delayed allergic reaction caused by amoxicillin and penicillin, that
      we all know as Flare up. We suggest that this phenomenon of Flare up occurs by a
      Type IV mechanism mediated by T-cells without participation of IgE antibodies.
      The betalactam hypersensitivity mechanism which has usually been described is an
      IgE mediated reaction, but there are other not very well known mechanisms that
      are responsible for the delayed reactions.

PMID- 16287549
TI  - Nimesulide-induced fixed drug eruption.
AB  - BACKGROUND: Nimesulide is a cyclooxygenase (COX) inhibitor with a high degree of
      selectivity to COX-2. It is a widely used and well tolerated nonsteroidal
      antiinflammatory drug that also has analgesic and antipyretic properties. The
      most frequently reported side effects concern the gastrointestinal tract.
      Pruritus and skin rash are the most common cutaneous adverse reactions. There are
      only eight cases of fixed drug eruptions due to nimesulide, described in the
      literature. CASE REPORT: The authors report a case of a patient with a history of
      antihistamine hypersensitivity who developed a bullous form of pigmented fixed
      drug eruption after nimesulide ingestion. Patch tests performed on residual skin
      lesion were positive to nimesulide, confirming that this was the culprit drug.
      CONCLUSIONS: Fixed drug eruptions are common cutaneous drug reactions, often
      misdiagnosed. A detailed anamnesis and physical examination are the key to
      suspect this condition.

PMID- 16287550
TI  - Occupational asthma due to carrot in a cook.
AB  - BACKGROUND: Few previous reports of carrot-induced asthma have been confirmed by
      objective tests. Hypersensitivity to carrot is frequently associated with allergy
      to Apiaceae spices and sensitization to birch and mugwort pollens. CLINICAL CASE:
      A 40-year-old cook woman was seen with sneezing, rhinorrhea, contact urticaria
      and wheezing within few minutes of handling or cutting raw carrots. She needed to
      leave out of the kitchen while the other cooks cut raw carrots. METHODS AND
      RESULTS: Skin tests were positive to carrot, celery, aniseed and fennel. Rubbing
      test with fresh carrot was positive. Specific IgE to carrot was 4.44 kU/L.
      Determinations of specific IgE to mugwort, grass and birch pollens were negative.
      Inhalative provocation test, performed as a handling test, was positive. The IgE
      immunoblotting showed two bands in carrot extract: a band with apparent molecular
      weight of 30 kd and other band of 18 kd. This band of 18 kd was Dau c 1. The band
      of 30 kd could correspond a phenylcoumaran benzylic ether reductase. Dau c 1 did
      not appear to be the unique allergen in this case. Additional allergens may
      induce the sensitization. Primary sensitization due to airborne allergens of
      foods and the lack of pollen allergy in this patient are notorious events.

PMID- 16287551
TI  - Severe anaphylactic reaction during the second infusion of infliximab in a
      patient with psoriatic arthritis.
AB  - A 33-yer-old woman with no history of atopy, diagnosed of psoriatic arthritis,
      received 200 mg I.V. infliximab, with previous oral administration of loratadine
      and betamethasone, that was well tolerated. Two minutes after a second infusion
      two weeks later, with the same pretreatment, the patients suffer dyspnea,
      laryngeal spasm, generalized tremor, vomiting, hypotension, sinusal tachycardia,
      anxiety and hyposemia. She recovered in 45 minutes, after the administration of
      I.V. hydrocortisone, chloropyramine, adrenaline and oxygen. Several reports of
      infliximab-induced anaphylactic reactions have been published, especially in
      patients with Crohn's disease, that have been attributed to a type I (acute or
      delayed) hypersensitivity reaction mechanism.

PMID- 16287552
TI  - [Guidelines for clinical updating in neurology].

PMID- 16287554
TI  - [Primary care research: are we doing what we should?].

PMID- 16287555
TI  - [Trends of non-steroidal anti-inflammatory drugs use in Spain, 1990 through
      2003].
AB  - OBJECTIVE: To know the trends of supply, consumption and pattern of use of non
      steroidal anti-inflammatory drugs (NSAIDs) in Spain from 1990 through 2003, as
      well as their costs. DESIGN: Drug utilization study. SETTING: National Health
      System, outpatient setting. MAIN MEASUREMENTS: Information on drug utilization
      was obtained from the ALHAQUEM database of the Spanish Ministry of Health, which
      contains the number of packages sold in community pharmacies and charged to the
      National Health System. Data were expressed in defined daily doses (DDD) per 1000
      inhabitants per day (DHD). RESULTS: NSAIDs consumption in Spain increased from
      23.67 DHD in 1990 to 45.82 DHD in 2003 (a 93.6% increase). Ibuprofen was the
      NSAID which showed the greatest increase (15.33 DHD in 2003). The consumption of
      coxibs reached a maximum of 7.74 DHD in 2001, but decreased to 3.59 DHD in 2003
      once prior-authorization programs were set up. Over the study period the share of
      NSAIDs use with a low gastrointestinal risk increased from 29% to 59%. Overall
      costs of NSAIDs increased from 117 million euro in 1990 to 329 million euro in
      2003. CONCLUSIONS: Over the study period the consumption of NSAIDs in Spain has
      increased twofold while costs increased threefold. The pattern of use has
      remarkably changed showing an increasing use of NSAIDs with a better
      gastrointestinal profile. The impact of coxibs marketing has been moderate.

PMID- 16287553
TI  - [Research in primary care: 1994-2003].
AB  - OBJECTIVES: To analyse the characteristics of the original articles published in
      the journal Atencion Primaria (Primary Care) during the last 10 years. DESIGN:
      Literature study. SETTING: Primary health care. PARTICIPANTS: Original articles
      published in Atencion Primaria between 1994 and 2003. MAIN MEASUREMENTS: The
      professional category of the authors, whether it was a multidisciplinary or
      multicentred study, the autonomous community of origin, the topic, the type of
      study, and if it had a grant or financial assistance. RESULTS: 1229 articles have
      been reviewed. In 40.0% of them a family doctor is included in the authorship.
      31.4% can be considered multidisciplinary and 20.5% multicentred. The Communities
      of Valencia, Madrid, Andalusia, and Catalonia took up 60% of the volume of
      publications. The most common topic is the provision and organisation of the
      health services (40.5%). Only 4.3% of the designs are experimental. A grant or
      financial aid is stated in 16.2% of the articles. CONCLUSIONS: Although the
      situation as regards the previous years has not varied too much, some positive
      findings, such as the emergence of research groups, increasing presence of
      multicentre and multidisciplinary studies, better access to sources of finance,
      etc, suggest that we are in a process of improving the quality of research in
      primary care.

PMID- 16287556
TI  - [Views, practices, barriers, and the will to change, when counselling to give up
      smoking is being given].
AB  - OBJECTIVE: To get to know the opinions, current practices, perceived barriers and
      stage of change in respect to the smoking cessation advice (SCA) offered to
      patients by the different health professionals (HP) from primary care. DESIGN:
      Descriptive cross-sectional study. LOCATION: Area Sanitaria 9's Health Centers,
      in Madrid, Spain. PARTICIPANTS: 480 HPs, including primary care doctors,
      pediatricians, primary care residents, and nursery staff. MEASUREMENTS: Using a
      self-filled and anonymous questionnaire, we will gather sociodemographic
      variables and from the HP's office, regarding the attitudes towards tobacco,
      efficiency beliefs and use of strategies in the advice, and the perceived
      barriers to give it, as well as the state of change. RESULTS: 75.2% of the HPs
      filled the questionnaire (94.2%, 61.1%, 51.6%, and 88% by doctors, nurses,
      pediatricians, and residents respectively). 72% ask regularly, this rate
      increasing to 92.4% over tobacco-related diseases. No differences were made
      between sexes, professional types, tobacco habits, or previous attendance to
      courses. 85.8% offers tracing and 63.5% give written advices. Nearly 75% of non
      smokers are considered social role models, that against only 40% of smokers. The
      main barriers found were lack of time and low motivation from the patients. 93.5%
      consider an specific education necessary to give efficient SCA. CONCLUSIONS:
      Inquiries are made and SCA is given, independently of the smoking habits of the
      SCA. Likewise, there is a good state of change by the HPs to optimize the
      treatment of tobacco dependency.

PMID- 16287557
TI  - [Relationship between the quality of professional life and the burnout of primary
      health care doctors].
AB  - OBJECTIVE: To know the relationship, if this exists, between the quality of
      professional life (CPL) and the burnout of primary health care staff. DESIGN:
      Transversal study employing CVP-35 test and MBI (Maslach Burnout Inventory), both
      sent by postmail. SETTING: 3 urban centers and 3 rural centers. Total: 131
      professionals. MEASURES: In the CVP-35 test, scores from 0 (minimum) to 100
      (maximum) are obtained. Maslach categorised each dimension into high, medium and
      low level. RESULTS: 71.7% answered. Medium age 44 years, average of 1339 sanitary
      cards. The number of visits/day was 37, home visits 1 per day. The CVP average
      was 4.48 (95% CI, 4.08-4.88). The damage perception in the post 5.9 (95% CI, 5.6
      6.1); the professional intrinsic motivation 6.5 (95% CI, 6.2-6.7), and the
      manager support 3.8 (95% CI, 3.6-4.1). MBI: high depersonalization 54.3%,
      emotional exhaustion (r=0.6; P<.0001), intrinsic motivation, and personal
      accomplishment (r=0.46; P<.0001) and professional quality of life front emotional
      fatigue (r= -0.4; P < .0005). CONCLUSIONS: CPL and burnout measure different but
      related dimensions. Therefore, its utility is dependent on the objectives. Target
      elements, which can improve the quality of professional life, can be identified
      from these tools.

PMID- 16287558
TI  - [Advances in computerising health systems].

PMID- 16287559
TI  - [On Balint groups, the Balint movement, and care of the doctor-patient
      relationship].

PMID- 16287560
TI  - [Contribution of primary health care to the resolution capacity of the health
      system and its measurement].

PMID- 16287561
TI  - [Effectiveness of advanced group and individual interventions in tackling tobacco
      dependency in primary care].
AB  - OBJECTIVES: To compare the effectiveness of group advanced intervention and
      individual advanced intervention for smoking management in primary health care;
      b) to know if in group intervention exists an added positive effect due of the
      group and, if this is true, to characterize it; and c) to know the advantages and
      inconvenients that the participants attribute to each intervention. DESIGN:
      Control clinic trial randomized in individual scale. SETTING: Mallorca primary
      health centers, Spain. PARTICIPANTS: Smokers >5 packet-year or monoxid carbon
      levels >15 ppm prepared for give up smoking. People younger than 18 years, people
      with terminal illness, and mental problems will be excluded. INTERVENTIONS:
      Candidates will be assigned to: a) group intervention; b) individual
      intervention; or c) short intervention or control group. Interventions will be
      done by a nurse and a general practitioner. Depth interview will be done for
      qualitative study. PRINCIPAL MEASUREMENT: Maintained cessation during 12 months
      confirmed by expired-air carbon monoxide measurement. SECONDARY MEASUREMENTS:
      Self-declared cessation and confirmed by expired-air carbon monoxide measurement
      months 1, 2, 3, 6, and 9, and tobacco reduction if there isn't abandonment.
      ANALYSIS: Intention treatment. Multilevel analysis will be done to determinate
      the positive effect added of the group if it's proved that exists. Content
      analysis for qualitative study. DISCUSSION: Randomization will prevent
      participants will be treated by their general practitioner o their nurse, this
      can mean worse results than results obtained in practice.

PMID- 16287562
TI  - [Mortality records in a health district].

PMID- 16287563
TI  - [Antiresorptive treatment after proximal femur fracture].

PMID- 16287564
TI  - [Profile of patients with sub-clinical hypothyroidism in primary care].

PMID- 16287565
TI  - [Evaluation of the levels of stress at work found in health professionals in
      health centres in Area IV of Asturias].

PMID- 16287566
TI  - [Frequency of attendance at primary care clinics. A new conceptual framework].

PMID- 16287567
TI  - [Those wonderful years].

PMID- 16287568
TI  - [Evaluation of response to neoadjuvant chemotherapy using breast scintigraphy in
      breast cancer].
AB  - BACKGROUND AND OBJECTIVE: We sought to evaluate the usefulness of Tc-99m
      sestamibi breast scintigraphy in predicting neoadjuvant chemotherapy response in
      patients with breast cancer. PATIENTS AND METHOD: In 50 consecutive patients with
      breast cancer stages II and III, physical examination, mammography and
      scintimammography were performed before and after the administration of
      neoadjuvant chemotherapy. The 3 assessments were compared for predictive value
      using a pathological response as reference. Values derived from visual assessment
      of the scintimammography, a quantitative tumor/background index, and isotope
      clearance were compared to the immunohistochemical expression of P-glycoprotein,
      vascular endothelial growth factor (VEGF) and microvessel density (CD31) in
      relation to neoadjuvant chemotherapy response. RESULTS: Macroscopic response was
      obtained in 10 cases (20%). Sensitivity was 86.5% (95% confidence interval [CI],
      70.4-94.9) for the physical examination, 83.3% (95% CI, 68-92.5) for the
      mammography and 76.5% (95% CI, 58.4-88.6) for the scintimammography. Specificity
      was 38.5% (95% CI, 15.1-67.7) for the physical examination, 42.9% (95% CI, 11.8
      79.8) for the mammography and 8.3% (95% CI, 0.4-40.2) for the scintimammography.
      There were no statistically significant differences in isotope uptake and
      clearance with regard to response nor in relation to levels of expression of P
      glycoprotein, VEGF and microvessel density. CONCLUSIONS: Breast scintigraphy with
      Tc-99m-sestamibi is not useful in predicting the response to neoadjuvant
      chemotherapy in breast cancer. Traditional physical examination and mammography
      are more effective. Isotope uptake and clearance do not predict response and
      there is not an effective in vivo measurement of chemo-resistance or tumor
      angiogenesis.

PMID- 16287569
TI  - [Risk factors for the development and persistence of asymptomatic bacteriuria in
      patients with type 2 diabetes].
AB  - BACKGROUND AND OBJECTIVE: To study the risk factors for the development and
      persistence of asymptomatic bacteriuria (AB) in type 2 diabetes mellitus (DM)
      patients from our health zone. PATIENTS AND METHOD: Observational and laboratory
      prospective cohort study. INCLUSION CRITERIA: women and men with type 2 DM from
      the 2 health centers of Petrer (Alicante). DATA: questionnaire including
      particular and epidemiological data. Laboratory values: biochemistry,
      glycosylated hemoglobin A1C, microalbuminuria, urinary sediment and urine
      culture. RESULTS: A total of 457 patients with type 2 DM were included; 63.2%
      women and 36.8% men. The prevalence of AB at baseline was 19.9% (25.6% in women
      vs 10.1% in men). 78.02% had persistence of AB after the twelve months of follow
      up; 21.7% developed symptomatic urinary tract infection (UTI) and 35.2% were
      treated with antimicrobial agents for any reason different from UTI during the
      follow-up period. The persistence of AB at the end of the study was 15.5%. Female
      sex (p = 0.04), leukocyturia (p = 0.008), urinary incontinence (p = 0.04) and
      elevated C reactive protein concentration (p = 0.009) remained significant risk
      factors for the presence and the persistence of AB when the multivariate
      logistical regression analysis was done. The presence of UTI within one year
      before the study started (p= 0.024) and previous antibiotic treatments (p = 0.04)
      were also independent significant factors associated with persistent AB. 84.5% of
      diabetic patients with persistent AB had the same infective organism in the urine
      culture as those found during the initial AB. CONCLUSIONS: In patients with type
      2 diabetes, female sex, urinary incontinence, leukocyturia, and elevated C
      reactive protein concentration were associated with development of AB. The same
      occurred with obesity in women and prostatic syndrome in men. The persistence of
      AB with the same species of isolated microorganisms as those found in AB at study
      entry is frequent, but it remains to be known if eradication of pathogens is more
      difficult in diabetic patients or, alternatively, if AB episodes are transient.

PMID- 16287570
TI  - [Effect on quality of life of nCPAP treatment in patients with obstructive sleep
      apnea].
AB  - BACKGROUND AND OBJECTIVE: The standard treatment of the obstructive sleep apnea
      syndrome (OSAS) is the nCPAP. There is evidence that its use improves the quality
      of life of patients. The objective of the study is to measure the effect of nCPAP
      on the quality of life of patients in a Spanish cohort. PATIENTS AND METHOD: We
      have used 3 quality of life questionnaires: SF-36, EuroQol 5D and FOSQ. OSAS
      patients were interviewed at baseline prior to the start of the treatment and at
      3 months follow-up. Two measures were employed to analyze the data: distribution
      based measures such as the effect size and instruments that evaluate the
      sensitivity to change of the questionnaires such as the ROC curves. RESULTS: We
      interviewed 124 patients. The benefit in terms of utility of the nCPAP was 0.03
      with SF-36 and 0.04 with EuroQol 5D. Effect size varies from small (0.21) with
      EuroQol 5D to moderate (0.51) with FOSQ. SF-36 obtained intermediate scores
      (0.35). EuroQol 5D was the questionnaire that obtained the biggest area under the
      ROC curve. Nevertheless, the area size was small in all cases. CONCLUSIONS: nCPAP
      improves significantly the quality of life of OSAS patients. The assessment of
      the quality of life of OSAS patients with the available instruments is only
      partially satisfactory.

PMID- 16287571
TI  - [Lung transplantation for emphysema].

PMID- 16287572
TI  - [Lung transplantation for emphysema: retrospective study of 65 patients].
AB  - BACKGROUND AND OBJECTIVE: Our goal was to analyze the incidence of perioperative
      complications in patients with pulmonary emphysema who underwent lung
      transplantation and to identify variables associated with the incidence of
      morbidity and mortality during the immediate postoperative period. PATIENTS AND
      METHOD: We undertook a retrospective study of 65 pulmonary emphysema patients who
      received lung transplants from 1994 through 2002 with the aim of determining the
      most common intra- and early postoperative complications in the ICU. An
      univariate analysis was carried out in order to identify variables associated
      with the incidence of mortality and postoperative complications. Those variables
      showing statistical significance underwent a multivariate analysis, by means of a
      pattern of logistic regression, in order to calculate the odds ratio and
      confidence interval. RESULTS: Seventeen patients received single-lung transplants
      (SLT) and 48 patients received sequential double-lung transplants (DLT).
      Intraoperative complications appeared more frequently in the DLT group. Most
      frequent complications during surgery were reperfusion syndrome (44.6%) and
      pulmonary hypertension (16.9%). The intraoperative survival was 100%. Fifty-five
      patients had some type of postoperative complication. Commonest postoperative
      complications were infection (56.9%) and primary graft failure (36.6%). In the
      early postoperative period the mortality rate was 16.9%. Main cause of death in
      the ICU was sepsis (54.5%). A time of mechanical ventilation > 48 hours and
      postoperative hemorrhage were the variables with a higher predictive value for
      mortality in the early postoperative period. CONCLUSIONS: Patients with SLT had a
      lower rate of perioperative complications and a higher survival during their stay
      in the ICU. Time of mechanical ventilation > 48 hours and postoperative
      hemorrhage were the variables that best predicted death in the early
      postoperative period following lung transplantation. Despite our experience,
      however, perioperative mortality in lung transplantation remains high up to this
      day.

PMID- 16287573
TI  - [Clinical laboratory: use and misuse, management models and health expenditure].

PMID- 16287574
TI  - [Recurrent miscarriage and inherited thrombophilia: diagnostic work-out and
      therapeutic management].
AB  - Pregnancy is a well recognized thrombophilic risk factor. Recurrent abortion (RA)
      affect up to 3% of fertile couples. A 50% of these cases are considered as
      idiopathic. Some of them may have one or more than one thrombophilic alterations.
      RA may be related to placental flow abnormalities. Up to 1% to 5% of all
      pregnancies may be complicated with placental flow abnormalities.
      Antiphospholipid syndrome, PS, PC, ATIII deficiencies, factor V, prothrombin,
      methylentetrahydrofolate reductase, plasminogen activator inhibitor type 1,
      fibrinogen and factor XIII polymorphisms, have been strongly related to bad
      obstetric outcomes, specially RA. The presence of more than one thrombophilic
      factor may be present in pregnant women, rising the risk of suffering RA. All
      pregnant patients and those who planed a future conception having a history of
      thrombotic events, independently of their previous obstetric outcomes, need to be
      studied for thrombophilia. All patients with RA specially if it appeared in the
      late-pregnancy, have also to be studied. Early antiaggregant and/or anticoagulant
      therapy, reduces the maternal-fetal risk.

PMID- 16287576
TI  - [Intestinal angiodysplasia and hypertrophic subaortic stenosis: is it a Heyde's
      syndrome variant?].

PMID- 16287575
TI  - [Efficacy of drugs "with a trophic action on the cartilage" in the treatment of
      osteoarthritis].

PMID- 16287577
TI  - [Whipple disease as a cause of fever of unknown origin].

PMID- 16287578
TI  - [Takayasu arteritis in a patient with Crohn's disease].

PMID- 16287580
TI  - [Pulmonary hypertension and Schonlein-Henoch syndrome].

PMID- 16287579
TI  - [Rheumatoid arthritis, methotrexate and non-Hodgkins lymphoma. A report of 3
      patients].

PMID- 16287581
TI  - [Paresthesias as initial manifestation of Gitelman's syndrome].

PMID- 16287582
TI  - [False positive result of PET scan in sarcoidosis].

PMID- 16287585
TI  - The evidence for early intervention.
AB  - It is believed that rheumatoid arthritis (RA) is the most common, potentially
      treatable cause of disability in the Western world. A commonsense approach to the
      management of a persistent, progressive, damaging condition such as RA would seem
      to be intervention before the onset of damage, at a stage when disease still may
      be reversible. Such a phase of disease has been described as a "window of
      opportunity" for intervention. This article discusses the evidence for early
      intervention in RA.

PMID- 16287586
TI  - Remodeling a rheumatology practice to facilitate early referral.
AB  - In the next 12 months, 7500 Canadians and 75,000 Americans will be afflicted with
      the onset of rheumatoid arthritis. Little is known about the health care use of
      patients with early RA. Nonetheless, rheumatologists and outcomes researchers
      strongly endorse the need for early diagnosis and treatment of this population.
      This article reviews trends and impediments to early referral of new-onset
      arthritis patients. The slow growth of early arthritis clinics is summarized in a
      survey that characterizes 23 early arthritis programs in North America. Also,
      several screening tools and models to capture these early-onset arthritis
      patients are presented.

PMID- 16287587
TI  - Early undifferentiated arthritis.
AB  - Patients who cannot be classified as having a well-defined arthropathy typically
      are labeled as having undifferentiated arthritis. Some patients develop
      sufficient features to permit classification, whereas others remain
      undifferentiated, but with persistent joint inflammation, functional disability,
      and development of radiographic damage. Identifying the subset of patients
      destined to develop rheumatoid arthritis, spondyloarthropathy, or a more severe
      and persistent form of undifferentiated arthritis and choosing appropriate
      treatment strategies remain challenges for clinicians. Numerous investigative
      strategies are available with which to characterize undifferentiated arthritis
      and assess prognosis. This article discusses the characteristics of
      undifferentiated arthritis at presentation and the investigative strategies that
      can be used to predict prognosis and outcome early in the disease course.
      Therapeutic strategies also are explored.

PMID- 16287588
TI  - Early oligoarthritis.
AB  - Oligoarthritis is a common condition, with a variable outcome, affecting a
      predominantly young population; when treated conventionally, oligoarthritis has a
      high morbidity. The variability of outcome has limited the development of studies
      evaluating therapies such as disease-modifying antirheumatic drugs in recent
      onset disease. Oligoarthritis is an important disease that warrants much greater
      study.

PMID- 16287589
TI  - Early psoriatic arthritis.
AB  - In the majority of patients with psoriatic arthritis (PsA), it is a chronic
      progressive disease, and only 12% of patients with early PsA will be in disease
      modifying antirheumatic drug-free remission at 2 years. Radiologic damage occurs
      in the early stages of PsA; up to 47% of patients with PsA have radiologic
      erosions after 2 years. This article reviews the clinical features of early PsA,
      pathologic insights into PsA gleaned from studies of early PsA, and the current
      state of diagnostic imaging and therapeutics in early PsA.

PMID- 16287590
TI  - Early rheumatoid arthritis.
AB  - Longitudinal and observational studies have provided important information on the
      course of rheumatoid arthritis (RA), clinical outcomes, and prognostic markers.
      In terms of clinical effectiveness of drugs used in RA, the results of such
      projects can be used to complement those of randomized studies. If well designed
      and conducted, inception cohorts are the most robust types of observational
      studies, reflect the most complete spectrum of disease, and provide the most
      reliable prognostic markers for the management of this chronic condition.

PMID- 16287591
TI  - Conventional x-ray in early arthritis.
AB  - This article reviews radiographic data from six cohorts of patients with early
      inflammatory arthritis. Of the patients, 8% to 15% had erosive disease at the
      first encounter with the rheumatologist. Classic scoring methods were applied to
      quantify damage, but baseline damage was low in early inflammatory arthritis.
      Yearly progression in damage score was assessed only in patients with high
      suspicion of rheumatoid arthritis at baseline or who had a final diagnosis of
      rheumatoid arthritis at follow-up and varied between 0.5% and 1.7% of the maximal
      damage of the scoring method per year. The large number of patients with zero
      values for erosions and lower progression rates will influence sample sizes in
      clinical trials in early inflammatory arthritis when including radiographic
      change as an outcome.

PMID- 16287592
TI  - MRI and musculoskeletal ultrasonography as diagnostic tools in early arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disorder
      primarily affecting the synovium and is characterized by destruction of bone and
      cartilage. Early diagnosis and treatment of RA can improve disease outcomes
      substantially. Magnetic resonance imaging and musculoskeletal ultrasonography may
      facilitate early diagnosis and aid the targeting of intensive therapy. Magnetic
      resonance imaging and musculoskeletal ultrasonography also are able to monitor
      temporal changes in disease activity (ie, synovitis) and damage (ie, erosions).
      These imaging modalities are likely to be increasingly used in the management of
      early rheumatoid arthritis to ensure the best patient outcomes, although more
      work is required to determine their optimal roles.

PMID- 16287593
TI  - Value of dual-energy x-ray absorptiometry as a diagnostic and assessment tool in
      early rheumatoid arthritis.
AB  - New research has revealed common pathophysiologic and cellular mechanisms behind
      the development of osteoporosis and joint damage in rheumatoid arthritis (RA).
      Because osteoporosis is a direct consequence of the inflammatory disease process,
      bone mass measurements in principle could be an outcome marker of inflammation,
      of damage, and of response to therapeutic intervention. Several devices have been
      developed for quantitative bone mass assessment including dual energy x-ray
      absorptiometry (DXA), which is considered the reference standard. This article
      based on current data and understanding discusses the use of DXA as a diagnostic
      and assessment tool especially in early RA.

PMID- 16287594
TI  - Conventional disease-modifying antirheumatic drugs in early arthritis.
AB  - This article reviews the use of conventional disease-modifying antirheumatic
      drugs (DMARDs) in the treatment of early rheumatoid arthritis (RA). The Finnish
      early RA cohorts are used as examples of how early and active treatment
      strategies have improved over time with increasing variety of available DMARDs.
      Therapy goals of early RA include remission to prevent severe long-term outcomes
      of RA. Remission can be achieved in a third of patients with early RA using a
      combination of conventional DMARDs, including methotrexate, sulfasalazine,
      hydroxychloroquine, and prednisolone. Of patients with early RA, 20% to 30% do
      not improve enough with conventional treatments and should be identified at early
      phases to consider institution of biologic agents.

PMID- 16287595
TI  - Biologics in early rheumatoid arthritis.
AB  - Treatment of patients with rheumatoid arthritis (RA) with disease-modifying
      antirheumatic drugs is started immediately after diagnosis, resulting in more
      effective suppression of disease activity and substantial reduction of joint
      damage. The development of biologic agents has enabled remission as a realistic
      therapeutic goal in a greater proportion of patients. The tumor necrosis factor
      alpha inhibitors, infliximab, etanercept, and adalimumab, have been studied in
      numerous randomized clinical trials. These agents can suppress disease activity
      directly, slow or stop progression of radiologic damage, and prevent further loss
      of quality of life. Patients treated with tumor necrosis factor-alpha inhibitors
      show few adverse events, which together with the high clinical effectiveness is
      favorable for treatment compliance. The exact role of these agents in the
      treatment of early-stage RA is unknown.

PMID- 16287596
TI  - Potential for altering rheumatoid arthritis outcome.
AB  - The potential for disproportionately altering outcome in the early stages of
      rheumatoid arthritis (RA) was first hypothesized in the early 1990s. This window
      of opportunity hypothesis for therapeutic intervention in RA is based on the
      existence of a time frame within which there is a potential for a greater
      response to therapy, resulting in sustained benefits or, perhaps most important,
      a chance of cure. Given the persistent, progressive, damaging, inflammatory
      nature of RA, this approach to altering outcome in the early stages seems
      attractive.

PMID- 16287597
TI  - Reuse of textile effluent treatment plant sludge in building materials.
AB  - This study examines the potential reuse of textile effluent treatment plant (ETP)
      sludge in building materials. The physico-chemical and engineering properties of
      a composite textile sludge sample from the southern part of India have been
      studied. The tests were conducted as per Bureau of Indian Standards (BIS)
      specification codes to evaluate the suitability of the sludge for structural and
      non-structural application by partial replacement of up to 30% of cement. The
      cement-sludge samples failed to meet the required strength for structural
      applications. The strength and other properties met the Bureau of Indian
      Standards for non-structural materials such as flooring tiles, solid and pavement
      blocks, and bricks. Results generally meet most ASTM standards for non-structural
      materials, except that the sludge-amended bricks do not meet the Grade NW brick
      standard. It is concluded that the substitution of textile ETP sludge for cement,
      up to a maximum of 30%, may be possible in the manufacturing of non-structural
      building materials. Detailed leachability and economic feasibility studies need
      to be carried out as the next step of research.

PMID- 16287598
TI  - Metal and organic matter contents in a combined household and industrial
      landfill.
AB  - A combined household/industrial landfill in a humid and cold temperate climate
      was characterised with respect to its chemical composition. Cores taken at three
      randomly chosen sites on the landfill and at different depths at each site were
      analysed. Carbon, nitrogen and pH were measured by standard laboratory methods.
      The chemical elements analysed included metals and the non-metals B, P and S. pH
      ranged between 8.0 and 8.5. The total carbon content was in the interval 4.5
      26.9% and the total nitrogen content in the interval 0.05-0.48%. The C/N ratio
      was high, indicating that there was not enough nitrogen available to ensure the
      stabilisation of carbon. The metal contents varied substantially. The water and
      carbon contents were related to each other as well as to the metal content, which
      increased with the content of water. Based on the results obtained regarding the
      chemical composition of the landfill, it is evident that the landfill consists of
      two layers. This indicates that the landfill body might have different levels of
      chemical development, due to water content, and different long-term leachability
      in the future.

PMID- 16287599
TI  - Carbon dioxide and ammonia emissions during composting of mixed paper, yard waste
      and food waste.
AB  - The objective of the work was to provide a method to predict CO2 and NH3 yields
      during composting of the biodegradable fraction of municipal solid wastes (MSW).
      The compostable portion of MSW was simulated using three principal biodegradable
      components, namely mixed paper wastes, yard wastes and food wastes. Twelve
      laboratory runs were carried out at thermophilic temperatures based on the
      principles of mixture experimental and full factorial designs. Seeded mixed paper
      (MXP), seeded yard waste (YW) and seeded food waste (FW), each composted
      individually, produced 150, 220 and 370 g CO2-C, and 2.0, 4.4 and 34 g NH3-N per
      dry kg of initial substrate, respectively. Several experimental runs were also
      carried out with different mixtures of these three substrates. The effect of
      seeding was insignificant during composting of food wastes and yard wastes, while
      seeding was necessary for composting of mixed paper. Polynomial equations were
      developed to predict CO2 and NH3 (in amounts of mass per dry kg of MSW) from
      mixtures of MSW. No interactions among components were found to be significant
      when predicting CO2 yields, while the interaction of food wastes and mixed paper
      was found to be significant when predicting NH3 yields.

PMID- 16287600
TI  - A kinetic analysis of solid waste composting at optimal conditions.
AB  - Six municipal solid waste (MSW) and yard waste components (food waste, mixed
      paper, yard waste, leaves, branches, grass clippings) were aerobically decomposed
      to measure the extent of decomposition under near optimal conditions.
      Decomposition was characterized by at least two principal stages, for most
      components, as was indicated by the carbon dioxide production rates. An aerobic
      biodegradation conceptual model is presented here based on the principle that
      solids hydrolysis is the rate-limiting step during solid waste composting. The
      mineralizable solid carbon of each solid waste component was assumed to comprise
      the readily, the moderately and the slowly (or refractory) hydrolysable carbons,
      each hydrolyzing at different rates to aqueous (water soluble) carbon. Aqueous
      carbon mineralizes to CO2 at rapid rates that are not rate-limiting to the
      process. Solids hydrolysis rate constants were calculated after fitting the
      experimentally determined carbon dioxide production rate data to model results.
      Hydrolysis rates for the readily hydrolysable carbon in all components ranged
      from approximately 0.06 to 0.1 d(-1); hydrolysis rates for the moderately
      hydrolysable carbon ranged from 0.005 to 0.06 d(-1). Leaves, branches and grass
      clippings did not have a readily hydrolysable carbon fraction, whilst the leaves
      and branches had the largest slowly hydrolysable carbon fractions (70%, 82%,
      respectively, of the total solid organic carbon). Grass and yard waste did not
      contain slowly hydrolysable carbon fractions. Food waste had the largest readily
      hydrolysable carbon fraction and produced the highest amount of CO2 among all
      substrates. Moderately hydrolysable solid carbon fractions ranged from 16% to 90%
      of the total solid organic carbon for all substrates used.

PMID- 16287601
TI  - The role of computational models in the search for the mechanical behavior and
      damage mechanisms of articular cartilage.
AB  - Articular cartilage plays a vital role in the function of diarthrodial joints.
      Due to osteoarthritis degeneration of articular cartilage occurs. The initial
      event that triggers the pathological process of cartilage degeneration is still
      unknown. Cartilage damage due to osteoarthritis is believed to be mechanically
      induced. Hence, to investigate the initiation of osteoarthritis the stresses and
      strains in the cartilage must be determined. So far the most common method to
      accomplish that is finite element analysis. This paper provides an overview of
      computational descriptions developed for this purpose, and what they can be used
      for. Articular cartilage composition and structure are discussed in relation with
      degenerative changes, and how these affect mechanical properties.

PMID- 16287602
TI  - Mistletoe treatment induces GM-CSF- and IL-5 production by PBMC and increases
      blood granulocyte- and eosinophil counts: a placebo controlled randomized study
      in healthy subjects.
AB  - OBJECTIVE: Various immunological effects have been reported during application of
      mistletoe preparations. Because these data are heterogeneous, we performed a
      placebo controlled study to investigate (1) effects on peripheral granulocyte and
      eosinophil counts, (2) related cytokine levels and (3) whether effects are
      related to mistletoe lectin (ML). METHODS: 43 volunteers were randomized to
      receive the mistletoe plant extract Iscador Quercus spezial (IQ), purified ML, IQ
      which was depleted from ML, or placebo subcutaneously twice per week for 8 weeks.
      Weekly, differential blood count and every four weeks spontaneous and IQ- and ML
      induced cytokine production by peripheral blood mononuclear cells (PBMC) were
      analyzed. RESULTS: Leukocyte-, granulocyte-, and eosinophil counts were
      significantly higher during treatment in the IQ- and ML-groups than in the
      placebo group. Furthermore, a significant increase of antigen-induced production
      of GM-CSF, IL-5 and IFNgamma by PBMC was observed in the IQ- and ML-group but not
      in the groups receiving ML-depleted IQ or placebo. Severe side effects did not
      occur in any of the subjects. CONCLUSIONS: Treatment with IQ or ML stimulates the
      production of GM-CSF, IL-5 and IFNgamma by PBMC, and this is accompanied by an
      increase of eosinophil- and granulocyte-counts. These observations may,
      therefore, open rational therapeutic indications for mistletoe extracts.

PMID- 16287603
TI  - Subcutaneous microdialysis for children - safe biochemical tissue monitoring
      based on a minimal traumatizing no touch insertion technique.
AB  - BACKGROUND: Microdialysis (MD) enables analysis of extracellular metabolites
      without performing blood tests. Changes in the concentration of various
      metabolites can be monitored frequently on almost every type of human tissue.
      Microdialysis of subcutaneous tissue (sc MD) is of particular significance in the
      case of pediatric patients because diurnal profiles can be generated without
      repeated blood sampling. There are only a few scientific articles that describe
      the application of sc MD on neonates, infants, or children. So far, side effects
      have not been investigated comprehensively. This prospective study scrutinizes
      side effects of sc MD in pediatric patients, focusing on a Minimal Traumatizing
      Insertion Technique of the MD catheter. PATIENTS AND METHODS: 42 pediatric
      patients within four age categories participated in the study which involved
      bedside monitoring using sc MD, including 5 extremely low birth weight (ELBW)
      infants with a body weight <1000g. A total of 48 sc MD catheters were inserted.
      Selection criteria were risk of hypoglycaemia (n = 29), elevated lactate levels
      (n = 16), or aminoacidopathies (n = 3). Duration of sc MD ranged from 1 to 16
      days. We used a Minimal Traumatizing Insertion Technique to safely insert the MD
      catheter into the subcutaneous tissue, characterized by blunt dissection of the
      tissue and by the use of a plastic cannula guidance to avoid desterilisation of
      the catheter. Complications and side effects related to sc MD were documented in
      standardized forms. RESULTS: The MD probe was easily placed even in the scanty
      adipose tissue of ELBW infants. During insertion of sc MD catheters accidental
      venous puncture occurred to 8%, and minor bleeding to 27%. Even with local
      anaesthesia insertion was painful for 40%. During the course of sc MD
      complications were rare: disturbance of perfusion flow 4%, catheter dislocation
      4%, local bleeding 4%. No signs of systemic or local infection were observed,
      there were no cases of local incompatibility. All catheters were withdrawn
      completely without leaving a scar. Repeated measurements allowed the generation
      of diurnal metabolic profiles. In some cases (respiratory chain complex I
      deficiency, PDH-deficiency) significant therapeutical effects on the patients'
      metabolism were demonstrated. CONCLUSIONS: The present study proves long-term sc
      MD to be suitable and safe for biochemical tissue monitoring. Using our insertion
      technique, it can be applied to children of all ages without causing discomfort
      or severe side effects. As it permits frequent sampling it allows evaluating and
      optimizing therapy and means a substantial progress for pediatric observation.

PMID- 16287604
TI  - Cerebral perfusion pressure for prediction of recurrent intracranial hypertension
      after primary decompressive craniectomy.
AB  - BACKGROUND: Decompressive craniectomy (DC) with dural grafting may be performed
      in patients with moderate (Glasgow-Coma-Scale [GCS] score 9-12 points) or severe
      traumatic brain injury (TBI; GCS score <or= 8 points) and threatening herniation.
      However, its effectiveness especially after primary craniectomy is still
      discussed due to missing evidence of improved outcome. The objectives of this
      study were to show the incidence of recurrent intracranial hypertension after
      primary DC, to identify predictive parameters for secondary DC, and to evaluate
      the long-term neurological performance 12 months after TBI. METHODS: Between
      01/1997 and 06/2001 all consecutive patients admitted with moderate or severe
      isolated TBI were enrolled in this study. They were treated according to the
      guidelines of the European Brain Injury Consortium, and the American Association
      of Neurosurgical Surgeons (AANS) for the management of severe TBI. Process and
      clinical data as well as every intervention were registered prospectively. The
      long-term neurological status was reassessed using the Glasgow Outcome Score
      (GOS) 12 months after TBI. Statistical comparison was performed using Mann
      Whitney-U test, and multivariate testing by means of logistic regression
      analysis. RESULTS: Fifty-one (43 males, 8 females; median age 51.4 years) of 119
      isolated TBI patients were included. Ten patients (8 males, 2 females; median age
      38.4 years) underwent secondary extended or contralateral DC in their clinical
      course. Three of them (30%) died at a median of 1 day after revision respectively
      6 days after TBI. According to univariate analysis, secondary DC significantly
      correlated with arterial hypotension (p = 0.020) and otorrhagia at admission (p =
      0.041), skull base fracture (p = 0.011) and decreased maximum cerebral perfusion
      pressure (CPP; p = 0.006) after primary surgery. Multivariate analysis identified
      decreased maximum CPP as the only independent predictive parameter (p = 0.036)
      for secondary DC and unfavourable GOS after 12-months follow-up. CONCLUSION:
      Arterial hypotension, otorrhagia at admission and skull base fractures are
      negatively influencing the mortality and morbidity of patients with isolated
      moderate or severe TBI. However, only decreased maximum CPP may independently
      indicate secondary DC after primary craniectomy in case of recurrent intracranial
      hypertension.

PMID- 16287606
TI  - Clinical situation of the coronal part of the teeth including restorations types
      placed prior to endodontic treatment - a retrospective study.
AB  - AIM: In the present retrospektive study the situation of the natural crown as
      well as the restoration types placed prior to endodontic treatment was examined.
      MATERIALS AND METHODS: A total of 782 teeth from 545 patients (54.3% men; 45.7%
      women; mean age: 49.9 +/- 12.1 years) were investigated. In addition to the
      evaluation of the medical history of the patients, x-rays and a clinical
      investigation were carried out in order to assess the clinical condition of the
      crown as well as the restoration types. Of special interest were: carious
      lesions, composite fillings, amalgam, ceramic or gold crowns and/or bridge
      restorations. RESULTS: 305 of the examined teeth were located in the mandible and
      477 in the maxilla. 26.3% of the teeth were anteriors, 31.2% were premolars and
      42.5% were molars. 24.2% of the teeth were restored with metal ceramic crowns,
      15.1% were restored with gold cast crowns or served as abutment teeth for
      bridgework; untreated caries was found in 21.1%, and composite fillings were
      found in 13.7% of the cases. 23.8% of the front teeth, 26.6% of the premolars and
      22.6% of the molars showed a metal ceramic restoration. 21% of all carious
      defects were found in the maxilla as well as in the mandible. CONCLUSIONS: In
      addition to the high number of untreated carious lesions, the presence of metal
      ceramics restorations was significantly higher than other restorations types.
      Carious lesions are main aetiological factors for endodontic measures, but also
      ceramic restorations including premature contacts have to be considered as causal
      factors for pulpal irritations.

PMID- 16287605
TI  - A population survey of sexual activity, sexual dysfunction and associated help
      seeking behavior in middle-aged and older adults in Germany.
AB  - The Global Study of Sexual Attitudes and Behaviors was a survey of 27,500 men and
      women aged 40 to 80 years in 29 countries. Here we report the sexual activity,
      the prevalence of sexual problems and related help-seeking behaviour among
      subjects in Germany. A telephone survey was conducted in 2001 and 2002, using a
      standardised questionnaire covering demographics, general health, relationships,
      and sexual behaviours, attitudes and beliefs. A total of 1,500 individuals in
      Germany (750 men and 750 women) completed the survey. Eighty-six percent of men
      and 66% of women had engaged in sexual intercourse during the year preceding the
      interview. The most common male sexual problems were early ejaculation (15%), a
      lack of sexual interest, erectile dysfunction and non-pleasurable sex (each 8%).
      The most common female sexual problems were a lack of sexual interest (18%), non
      pleasurable sex (14%) and lubrication difficulties (13%). Most sexual problems
      were less common among men and women in Germany than in other European regions.
      Increasing age was a significant predictor of a lack of sexual interest and
      erectile difficulties in men. Only 18% of men and 15% of women had talked to a
      doctor about their sexual problem(s). In conclusion, many middle-aged and older
      German adults reported continued sexual interest and activity. Overall, sexual
      problems were less prevalent in Germany compared with other European regions. Of
      those who experienced sexual problems, however, few had sought medical help. This
      was often due to a lack of perception of a problem.

PMID- 16287607
TI  - Prevalence of oral lesions and periodontal diseases in HIV-infected patients on
      antiretroviral therapy.
AB  - A cross-sectional study examining oral manifestations was carried out in HIV
      infected patients of a general HIV-specialized unit to provide prevalence data on
      oral lesions and periodontal diseases. The occurrence of oral lesions was
      correlated with demographic and clinical characteristics, immunologic and
      virologic parameters. Among 139 patients 86% presented any oral lesions with a
      prevalence of 76% of any periodontal diseases. Most periodontal lesions were
      classified as conventional gingivitis (28%) or periodontitis (30%). Dental plaque
      formation was associated with a higher prevalence of periodontal diseases (p =
      0.01) and periodontal inflammation scores were higher in patients with more
      reduced CD4-counts (p = 0.03). Prevalence for HIV-specific oral lesions was 29%
      with a proportion of 9% of linear gingival erythema (LGE), 3.6% of necrotizing
      and ulcerative gingivitis (NUG) or periodontitis (NUP), 7% of oral candidiasis,
      3.6% of oral hairy leucoplakia (OHL) and single other lesions. HIV-specific
      lesions (NUG/NUP, oral candidiasis and OHL) were found predominantly in patients
      with advanced immunosuppression and elevated viral load. Compared with data of
      oral diseases of the pre-HAART era prevalence of HIV-specific lesions was
      markedly reduced. Especially frequently known lesions such as oral candidiasis
      and OHL were less common seen. We noticed a shift of prevalence towards
      periodontal diseases. Lack of oral hygiene determined by plaque formation and
      reduced CD4-counts with pronounced periodontal inflammation can be seen as risk
      factors for periodontal disease. Overall high prevalence of manifestations
      underlines the importance of oral examination for the general practitioner and
      visits by oral specialists should become a routine procedure in HIV-patients
      care.

PMID- 16287608
TI  - Therapeutic response of rosacea to dobesilate.
AB  - Despite an incomplete understanding of the pathogenesis of rosacea, therapeutic
      modalities continue to expand. The principal subtype of rosacea includes
      erythematotelangiestatic rosacea, which is characterized by uncontrolled
      angiogenesis. Angiogenic growth factors such as fibroblast growth factors (FGF)
      and vascular endothelial growth factor (VEGF) are currently targets of intense
      effort to inhibit deregulated blood vessel formation in diseases such as cancer.
      Here we report a 33-years-old woman with erythematotelangestatic rosacea who
      responds to a daily treatment of topically applied dobesilate, an inhibitor of
      FGF, with an improvement in erythema and telangectasia after two weeks. Thus,
      dobesilate might be useful in the treatment of rosacea and other diseases that
      depend on pathologic angiogenesis.

PMID- 16287610
TI  - Effect of the psoralen-based photochemical pathogen inactivation on mitochondrial
      DNA in platelets.
AB  - Photochemical treatment (PCT) of platelet concentrates, using amotosalen HCl and
      UVA-light, inactivates pathogens by forming adducts between amotosalen and
      nucleic acids. The impact of the photochemical treatment on pathogens and
      leukocytes has been studied extensively. Yet little is known about the effect of
      PCT on nucleic acids in platelets. Platelets contain viable mitochondria and
      mitochondrial DNA (mtDNA) and this study aimed at evaluating the amotosalen
      modifications on platelet mtDNA. We applied two independent but complementary
      molecular assays to investigate qualitative as well as quantitative aspects of
      the psoralen-mediated DNA modifications in platelet mtDNA. The amotosalen-DNA
      modification density was measured using (14)C-labeled amotosalen. Amotosalen (150
      microM) yielded 4.0 +/- 1.2 psoralen adducts per 1,000 bp in mtDNA after
      irradiation with 3 J/cm(2) UVA. Furthermore, we tested if the PCT-induced DNA
      modifications could be detected by a PCR assay. On the basis of PCR inhibition
      due to amotosalen-DNA adducts, mtDNA-specific PCR assays were developed and
      tested for their specificity and sensitivity. Our data revealed that mtDNA in
      platelets is substantially modified by PCT and that these modifications can be
      documented by a PCR inhibition system.

PMID- 16287611
TI  - Treadmill exercise in claudicants on aspirin results in improved antioxidant
      status but only minimal platelet activation.
AB  - The consequence of exercise on platelets remains controversial and adverse
      effects may result from repeated ischaemia reperfusion injury. We investigated
      platelet activation (platelet P-selectin (PS), and activated glycoprotein (Gp)
      IIb/IIIa), platelet-monocyte aggregates (PMA) and total plasma antioxidant status
      (TPAS) in claudicants after exercise. Twenty claudicants, taking 75 mg of aspirin
      daily, were subjected to repeated treadmill testing (3 km/h, 10% inclination).
      Blood was sampled before and after exercise. Activated GpIIb/IIIa, PS and PMA
      were quantified with flow cytometry. TPAS was quantified using a decolourisation
      assay. Percent positive cells for PS (pre-exercise 3.76% vs. 40 min post-exercise
      4.10%; P < 0.05) and platelet-monocyte aggregates (pre-exercise: 25.31% vs. 40
      min post-exercise 26.99%; P < 0.05) were significantly higher after exercise.
      Relative median fluorescence (RMF) for activated GpIIb/IIIa was significantly
      higher 40 min after exercise (pre-exercise: 3.04 vs. 40 min post-exercise: 4.01;
      P < 0.05). TPAS was significantly higher post-exercise (pre-exercise: 1.31 mmol/l
      vs. 1 min post-exercise: 1.40 mmol/l and 40 min post-exercise: 1.38 mmol/l; P <
      0.01). Following moderate exercise, 'aspirin treated claudicants' show marginal
      platelet activation, PMA formation and a favourable improvement in antioxidant
      status. Further studies are required to assess the effect of additional
      antiplatelet agents and the significance of platelet-monocyte interactions. The
      possibility that aspirin contributes to the TPAS changes following exercise needs
      to be investigated.

PMID- 16287612
TI  - Efficient tyrosine phosphorylation of proteins after activation of platelets with
      thrombin depends on intact glycoprotein Ib.
AB  - The role of platelet glycoprotein Ib as a thrombin receptor has been often a
      subject of controversy. We have investigated the role of the thrombin receptors,
      GPIb and protease-activated receptor (PAR)-1. Tyrosine phosphorylation in whole
      platelet lysates and in cytoskeletal extracts was evaluated after activation with
      thrombin and with the thrombin receptor-activating peptide (TRAP). Different
      experimental approaches were applied including: (i) congenital deficiency of
      platelet GPIb (Bernard Soulier syndrome, BSS), (ii) antibody to GPIb (AP1), (iii)
      selective protease cleavage (metalloprotease), and (iv) antibody to (PAR)-1.
      After activation of control platelets with thrombin or TRAP, multiple proteins
      became tyrosine phosphorylated in platelet lysates and some of them associated
      with the cytoskeletal fraction. These effects were absent in BSS platelets.
      Presence of AP1 or metalloprotease treatment showed an inhibitory effect when
      platelets were activated with a low concentration of thrombin or TRAP. Blockade
      of PAR-1 with a specific antibody, SPAN 12, inhibited platelet response to both
      agonists. This study reinforces the hypothesis that GPIb is the high-affinity
      receptor for thrombin. The signaling mechanisms occurring through tyrosine
      phosphorylation of proteins triggered by thrombin seem to be dependent on intact
      GPIb. Moreover, our results indicate that both receptors, GPIb and PAR-1, are
      necessary to achieve a full platelet response to thrombin.

PMID- 16287613
TI  - Two distinct subgroups of tirofiban-induced thrombocytopenia exist due to drug
      dependent antibodies that cause platelet activation and increased ischaemic
      events.
AB  - Tirofiban-associated thrombocytopenia is due to drug-dependent antibodies (DDAbs)
      directed against the GPIIb/IIIa complex which can bind after drug-induced
      conformational changes to the receptor complex. In such cases a higher incidence
      of myocardial infarction and mortality has been reported raising the possibility
      of platelet activation. We followed consecutive cases treated with tirofiban to
      determine the incidence of thrombocytopenia and confirmed that this was due to
      tirofiban-dependent antibodies. We then tested if these antibodies could cause
      platelet activation in vitro and correlated this with clinical outcome. In 871
      treated patients, severe thrombocytopenia was observed in 11 cases, an incidence
      of 1.26%. Tirofiban dependent antibodies were confirmed in all cases using a flow
      cytometric assay. There were two distinct presentations of thrombocytopenia, one
      occurring acutely, and the second a delayed thrombocytopenia occurring after
      several days of tirofiban exposure and in keeping with a primary immune response.
      The effects of DDAbs on platelet activation was analysed by measuring P-selectin
      (CD62p) and annexin V, in the presence or absence of tirofiban, by flow
      cytometry. In addition, platelet activation was sought using the serotonin
      release assay. In six cases there was evidence of platelet activation and this
      was significantly associated with further coronary ischaemic events experienced
      at the time of acute thrombocytopenia. Tirofiban-induced thrombocytopenia due to
      DDAbs is a common occurrence and can lead to platelet activation and increased
      thrombotic events.

PMID- 16287614
TI  - Inhibitory effect of aqueous extracts of some herbs on human platelet aggregation
      in vitro.
AB  - Effect of aqueous extract of several herbs on human platelet aggregation in vitro
      was investigated. Out of 28 herbs/nutriceuticals investigated, camomile, nettle
      alfalfa, garlic and onion exhibited most significant anti-platelet activity
      (>or=45% inhibition). Aqueous extracts of alfalfa, fresh nettle, and camomile
      inhibited ADP induced-platelet aggregation by 73, 65 and 60%, respectively,
      compared with control (P < 0.05). Camomile and alfalfa inhibited collagen-induced
      platelet aggregation by 84 and 65%, respectively, but nettle could not inhibit
      collagen-induced aggregation. In contrast, nettle was the most potent inhibitor
      (66%) of whole blood aggregation induced by collagen, followed by alfalfa (52%),
      and camomile (30%) compared with control (P < 0.05). None of these three herbs
      however could inhibit arachidonic acid or thrombin induced platelet aggregation.
      Camomile and alfalfa strongly inhibited thromboxane B2 synthesis induced by ADP
      or collagen, but nettle had no effect. Alfalfa and nettle increased cGMP levels
      in platelets by 50 and 35%, respectively, compared with the control (1.85 +/-
      0.23 nM) (P < 0.005). All these data indicate that camomile, nettle and alfalfa
      have potent anti-platelet properties, and their inhibitory actions are mediated
      via different mechanisms.

PMID- 16287615
TI  - Effect of neutrophil adhesion on the size of aggregates formed by agonist
      activated platelets.
AB  - In this study we have investigated the effect of human neutrophil on agonist
      induced platelet aggregation by using the laser-light scattering method that can
      detect a two-phase process, formation of small aggregates followed by large
      aggregate formation. When nonstimulated neutrophils were added to agonist
      stimulated platelet-rich plasma (PRP), the large platelet aggregates were
      decreased and the small ones were increased by using either collagen, thrombin or
      ADP as agonist. Scanning-electron microscopic observation showed marked adhesion
      of neutrophil to aggregated platelets. The supernatant from neutrophils cell
      lysate (neutrophil supernatant) showed inhibitory effect similar to that with
      intact neutrophils, suggesting that the inhibitory effect by neutrophils was due
      to soluble component(s) including proteases released from neutrophils adhered to
      activated platelets. We have examined the effect of inhibition of a major
      released protease, elastase. The addition of its potent inhibitor elafin to
      intact neutrophils or the neutrophil supernatant changed their antiaggregating
      activity. The treatment of platelets with genistein, an inhibitor of protein
      tyrosine kinase, decreased agonist-induced large aggregates and increased small
      ones, suggesting that certain protein tyrosine kinase would be involved in the
      transition from small to large platelet aggregates. It was also shown that the
      tyrosine phosphorylation induced by agonist stimulation of several high molecular
      weight proteins of platelets was inhibited by coincubation with neutrophils,
      concurrent with increases in smaller phosphorylated proteins. In washed
      platelets, coincubation with neutrophils resulted in reduced formation of large
      aggregates when stimulated with collagen or thrombin and repressed agonist
      induced activation of tyrosine protein kinases (Syk, Lyn, Src, and Pyk2), but not
      thrombin-induced ERK and p38 MAP kinase. These results suggest that the cleavage
      of platelet membrane glycoproteins at least in part by elastase which was
      released from neutrophils, is involved in the inhibition of the transition from
      small to large platelet aggregates.

PMID- 16287616
TI  - Pharmacodynamics of two different dosing regimens of tirofiban in citrate or
      PPACK anticoagulated blood.
AB  - The primary objective of this study was to compare the inhibitory activity of
      tirofiban measured with the rapid platelet function assay (RPFA) and with light
      transmission aggregometry using two different anticoagulants (citrate versus
      PPACK). Twenty patients treated with tirofiban for percutaneous coronary
      intervention were studied at six time points during tirofiban treatment.
      Tirofiban was given with a bolus dose of 10 microg/kg and an infusion of 0.10
      microg/kg per min (10 patients) or with a bolus dose of 15 microg/kg and an
      infusion of 0.15 microg/kg per min (10 patients). Inhibition of platelet function
      appeared highest using citrated blood and the RPFA-device and lowest when
      assessed by aggregometry in PPACK-anticoagulated blood. Only the higher dose of
      tirofiban achieved an inhibition of platelet aggregation of at least 80% in all
      test systems.

PMID- 16287617
TI  - Peripheral neuropathy is associated with increased mean platelet volume in type 2
      diabetic patients.

PMID- 16287618
TI  - Platelet secretory granules or secretory lysosomes?

PMID- 16287619
TI  - BSS-HMM3s: an improved HMM method for identifying transcription factor binding
      sites.
AB  - Today, an important problem in molecular biology is the study of gene expression
      mechanism. The first step in determining differential gene expression is the
      binding of sequence specific transcription factors to regulatory regions of the
      genes. An important aspect to understand how a given transcription factor
      functions is to know the entire gamut of binding sites and potential target genes
      that the factor may regulate. In this paper, we presented an improved prediction
      method based on hidden Markov model (HMM) called BSS-HMM(3)s (binding site search
      based on third-order HMMs) for transcription factor binding sites. The results
      show that the predicted sensitivity and specificity of BSS-HMM(3)s increased
      11.95 and 12.97%, respectively, compared with Match.

PMID- 16287620
TI  - Cloning and sequence analysis of myostatin promoter in sheep.
AB  - To better understand the structure and function of the myostatin's gene promoter
      region in sheep, we cloned and sequenced a 1.517 kb fragment containing the 5'
      regulatory region of the sheep myostatin gene (GenBank accession number is
      AY918121). The promoter sequence consists of three TATA boxes, one CAAT box, and
      eight putative E-boxes. Some putative muscle growth response elements for Octamer
      binding factor 1(Octamer), Activator protein 1(AP1), Growth factor independence 1
      zinc finger protein (Gfi-1B), Myocyte enhancer factor 2 (MEF2), Muscle-specific
      Mt binding site (MTBF), Glucocorticoid response elements (GRE) and Progesterone
      receptor binding site (PRE) were detected. Some of the motifs are conserved as
      compared to with that in the goat, bovine and porcine myostatin promoters.
      However, some differences were also found.

PMID- 16287621
TI  - Characterization and expression of AmphiARF gene encoding a new member of ARF
      family from amphioxus Branchiostoma belcheri tsingtauense.
AB  - The cDNA AmphiARF, encoding a novel member of ARF family was for the first time
      identified from the gut cDNA library of amphioxus Branchiostoma becheri
      tsingtauense. The deduced amino acid sequence includes the motifs involved in GTP
      binding (DVGG, NKQD and SAK) and hydrolysis (GXDXXGK), and a glycine at position
      2 for N-terminal myristoylation, which are all characteristic of ARFs. However,
      it has a 46 amino acid C-terminal extension (positions 183-227), which was not
      found in any ARF family previously described including ARF-like proteins. This
      suggests that AmphiARF is a new member of ARF family, which was also supported by
      the phylogenetic analysis. It is highly likely that the extended C-terminal of
      AmphiARF is a novel addition occurring after cephalochordate/vertebrate split.
      Northern blotting analysis revealed that AmphiARF transcript was present in all
      tissues examined, consistent with the involvement of ARFs in the fundamental role
      like vesicular trafficking of proteins.

PMID- 16287622
TI  - The microsatellites and minisatellites in the genome of Fenneropenaeus chinensis.
AB  - Through two-time sequencing randomly in Fenneropenaeus chinensis, 2,597,000 bp
      cumulative length random genomic sequences about occupying 1.23 per thousand of
      the entire genome are obtained, in which the length of the first time sequencing
      is 884,000 bp, by cutting the genome DNA with Sau3AI enzyme, and the second is
      1,713,000 bp by breaking the genome DNA with the physical method, ultrasonic.
      Using tandem repeat finder (TRF) soft to analyze the sequences, 4,588 tandem
      repeats are found, in which the number of microsatellites (1-6 bp) is 3,888, and
      700 for minisatellites ( >or= 7 bp). The cumulative length of repeats is 305,555
      bp, accounting for 11.72% of total cumulative sequence length, in which the
      cumulative length of microsatellites is 232,979 bp, accounting for 8.97% of total
      sequence length, and greater than those of other organisms, such as human and
      mosquito, etc. The dinucleotide repeat type is dominant in which the dominant
      repeat class is AT. The second abundant repeat type is trinucleotide, of which
      the dominant repeat class is AAT. Interestingly, of all of repeat types, the
      repeat numbers and repeat classes of primer number repeat types, such as
      pentanucleotide, heptanucleotide, elevennucleotide, etc. are less than those of
      repeat types beside them. The phenomena may involve the genesis and the evolution
      of microsatellites and minisatellites.

PMID- 16287623
TI  - Isolation and sequence analysis of P450 genes from a pyrethroid resistant colony
      of the major malaria vector Anopheles funestus.
AB  - Pyrethroid resistance has been demonstrated in populations of Anopheles funestus
      from South Africa and southern Mozambique. Resistance is associated with elevated
      P450 monooxygenase enzymes. In this study, degenerate primers based on conserved
      regions of Anopheles gambiae P450 CYP4, 6 and 9 families were used to amplify
      genomic and cDNA templates from A. funestus. A total of 12 CYP4, 12 CYP6 and 7
      CYP9 partial genes have been isolated and sequenced. BLAST results revealed that
      A. funestus P450s generally have a high sequence identity to A. gambiae with
      above 75% identity at the amino acid level. The exception is CYP9J14. The A.
      gambiae P450 showing highest identity to CYP9J14 exhibits only 55% identity
      suggesting that CYP9J14 may have arisen from a recent duplication event.
      Molecular phylogenetic analysis based on amino acid sequences also supported this
      hypothesis. Intron positions, but not size, were highly conserved between the two
      species. The high level of orthology that exists in the P450 gene families of
      these two species may facilitate the prediction of individual P450 protein
      function.

PMID- 16287624
TI  - Casein kinase 2 during early embryonic development in silkworm Bombyx mori: cDNA
      sequence, gene expression, and enzyme activity.
AB  - To clarify the property of casein kinase 2 (CK2) during early embryonic
      development in the silkworm, we compared the phosphorylation activities of CK2 in
      non-diapause and diapause eggs until 60 h after oviposition. In nondiapause eggs,
      the phosphorylated signals were found at each stage and became progressively
      stronger through each stage. On the other hand, in diapause eggs, the strongest
      phosphorylated signals were found at approximately 12 to 24 h after oviposition
      and became progressively weaker through each stage. To clarify the control
      mechanism of these enzyme activities, we tried to clone cDNAs encoding alpha- and
      beta-subunit of CK2 and analyze the gene expressions. The deduced amino acid
      sequence of the isolated cDNAs comprised 342 and 220 residues, and these
      sequences showed 85-90% identities to the alpha- and beta-subunit of CK2 in
      Spodoptera frugiperda. RT-PCR indicated that these genes were expressed in
      nondiapause and diapause eggs. However, these genes expressions were not parallel
      with the changes in CK2 activity. These results suggest that the changes in CK2
      activity are regulated mainly at the level of post-transcription during embryonic
      development in Bombyx mori.

PMID- 16287626
TI  - Heterozygous indels as useful tools in the reconstruction of DNA sequences and in
      the assessment of ploidy level and genomic constitution of hybrid organisms.
AB  - In this paper we describe a simple approach using double peaks in chromatograms
      generated as artefacts in the vicinity of heterozygous indels, to identify the
      specific sequences present in individual strands of a given DNA fragment. This
      method is useful to assign bases in individuals that are heterozygous at multiple
      sites. In addition, the relative sizes of the double peaks help to determine the
      ploidy level and the relative contribution of the parental genomes in hybrids.
      Our interpretation was confirmed with the analysis of artificial mixtures of DNA
      of two different species. Results were robust with varying PCR and sequencing
      conditions. The applicability of this method was demonstrated in hybrids of the
      Squalius alburnoides complex and in heterozygotes of Chondrostoma oligolepis. Far
      from being limited to these fish models and the gene where it was tested (beta
      actin), this sequence reconstruction methodology is expected to have a broader
      application.

PMID- 16287625
TI  - Molecular cloning, expression and mapping analysis of a novel cytosolic ascorbate
      peroxidase gene from tomato.
AB  - Ascorbate peroxidase (APX, EC 1.11.1.11) plays a major role in H(2)O(2)
      scavenging in plants and can help to avoid reactive oxygen species (ROS) damage.
      A new cytosolic APX gene was cloned from tomato (designated LecAPX2) by RACE-PCR.
      The full-length cDNA of LecAPX2 contained a complete open reading frame (ORF) of
      753 bp, which encoding 250 amino acid residues. Homology analysis of LecAPX2
      showed a 94% identity with potato cAPX gene and 92% identity with another tomato
      cAPX gene (APX20), the deduced amino acid showed 88% homology with APX20 protein
      and 75-92% identity with cAPX from other plants such as potato, tobacco,
      broccoli, spinach, pea, rice, etc. LecAPX2 revealed the existence of a haem
      peroxidase and plant APX family signatures. Northern blot analysis showed that
      LecAPX2 was constitutively expressed in root, stem, leaf, flower and fruit of
      tomato, whereas the expression levels were different. LecAPX2 was mapped to 6-A
      using 75 tomato introgression lines (ILs), each containing a single homozygous
      RFLP-defined chromosome segment from the green-fruited species Lycopersicon
      pennellii.

PMID- 16287627
TI  - cDNA sequence of the horse (Equus caballus) LAMA3 gene and characterization of
      two intronic SNP markers.
AB  - Laminins are large heterotrimeric basement membrane glycoproteins composed of
      alpha, beta and gamma chains. The Laminin 5 isoform has an alpha3beta3gamma2
      composition and is essential for the adhesion of basal keratinocytes to the
      underlying epithelial basement membrane where it is mainly located. Mutations in
      the genes coding for the 3 chains have been associated with a severe skin
      blistering disease, Herlitz's junctional epidermolysis bullosa (JEB), observed in
      different species as man, dog, cat and horse. In this study, we report the
      sequence of the 5.2 kb horse laminin alpha 3 cDNA (LAMA3) as well as the
      detection of two intronic SNPs. These data will be useful to further identify
      causal mutations for the disease in this gene.

PMID- 16287628
TI  - Nucleotide sequence for cDNA of bovine mitochondrial ATP-dependent protease and
      determination of N-terminus of the mature enzyme from the adrenal cortex.
AB  - We have determined the cDNA sequence encoding bovine mitochondrial ATP-dependent
      Lon protease. Since the 5'-end region of the cDNA was highly GC-rich and thus
      could not be amplified by the 5'-RACE method, a genomic DNA fragment containing
      an in-frame ATG was isolated and sequenced. The translated amino acid sequence
      contained 961 amino acids with a calculated molecular weight 106,665. Sequence
      similarities of the bovine enzyme to human and E. coli orthologs were 92 and 27%,
      respectively. The N-terminal amino acid sequence seemed to be a mitochondrial
      targeting signal. To determine the cleavage site of the signal sequence we
      analyzed the mature enzyme purified from bovine adrenocortical mitochondria.
      Analysis of CNBr-digested peptides revealed that the N-terminus was
      heterogeneous. We suggest that nonspecific aminopeptidase might remove several
      amino acids from the N-terminus after mitochondrial processing peptidase has
      cleaved Gly(67)-Leu(68) or Leu(68)-Trp(69).

PMID- 16287629
TI  - The test-retest reliability of a standardized neurocognitive and
      neurophysiological test battery: "neuromarker".
AB  - NeuroMarker combines EEG and ERP measures with neurocognitive tests in a fully
      computerized and standardized testing system. It is designed for use across the
      lifespan and has a large normative database of over 1,000 subjects. This study
      was a preliminary evaluation of "NeuroMarker" in subjects spanning four decades.
      Twenty-one healthy subjects (12-57 years) were tested at baseline and four weeks
      later. From the "Neuromarker" battery, the authors analyzed EEG data (eyes open
      and closed) and ERPs elicited during auditory oddball (N100, P200, N200, P300)
      and working memory (P150, P300) tasks. Concomitant neuropsychological data,
      acquired using a touch-screen system, comprised measures of sensori-motor,
      attention, verbal, executive, and memory function. Test-retest data were examined
      using analyses of variance and correlational procedures (corrected for multiple
      comparisons), with parallel analyses of age. EEG data did not differ across
      sessions, and showed high test-retest reliability (.71-.95), particularly for
      theta and delta (>.85). ERP components also showed sound reliability,
      particularly for sites where components are maximal: fronto-central N100 (.76
      .77), centro-parietal P300 (.78-.81) to oddball targets, N100 and P200 (.74-.86)
      to oddball non-targets, and P150 amplitude and latency (.84-.93) to working
      memory stimuli. Neuropsychological tests showed a similarly sound level of
      consistency (on average, .70), with the most consistent tests tapping simple
      motor function, estimated intelligence, switching of attention (Part 2), verbal
      interference response time and memory intrusions (.71-.89). Age and sex did not
      have a differential impact on reliability for EEG, ERP, or neuropsychology
      measures. These findings provide preliminary evidence that the "NeuroMarker"
      battery is reliable for test-retest assessments. The results suggest that the
      standardized approach has utility for providing sensitive clinical and treatment
      evaluations across age groups.

PMID- 16287630
TI  - Sex differences in perceptual processing: performance on the color-Kanji stroop
      task of visual stimuli.
AB  - During color, colored Kanji characters and Stroop task of the visual stimuli, the
      P300 component of the event-related brain potential (ERPs) was used in
      conjunction with response time to identify sex differences in perceptual
      processing. Participants were instructed to respond to the display colors and
      name colored Kanji characters as quickly as possible in the respective stimulus
      conditions. Response time varied in all stimulus conditions, the males took
      longer than females. The P300 latency of males was longer and amplitude was
      smaller than females. The results suggest that cognitive strategy of males is
      different from females.

PMID- 16287631
TI  - Right basal ganglion hypoperfusion in obsessive compulsive disorder patients
      demonstrated by Tc-99m-HMPAO brain perfusion spect: a controlled study.
AB  - The aim of this study is to demonstrate the regional cerebral blood flows (rCBF)
      of obsessive-compulsive disorder (OCD) patients compared to controls by using Tc
      99m-HMPAO SPECT. Sixteen OCD and seven control subjects were admitted into the
      study. Yale-Brown Obsessive Compulsive Rating Scale (Y-BOCS), Hamilton Depression
      Rating Scale (HDRS), and Hamilton Anxiety Rating Scale (HARS) were applied to the
      patients. The rCBF was found to be decreased in right basal ganglion in OCD
      patients. The right basal ganglion rCBF was negatively correlated with Y-BOCS
      total and compulsion scores. The left thalamus rCBF was negatively correlated
      with Y-BOCS obsession score. Right and left cingulate rCBF were negatively
      correlated with HDRS score. The results indicating hypoperfusion in right basal
      ganglion in OCD patients support previous findings about dysfunction of frontal
      subcortical circuits in this disorder.

PMID- 16287632
TI  - Vascular dementia and Alzheimer's disease: the unsolved problem of clinical and
      neuropsychological differential diagnosis.
AB  - The definition of clinical criteria for differential diagnosis of Vascular
      Dementia (VaD) and Alzheimer's disease (AD) remains controversial. A large group
      of patients selected was affected by chronic cerebrovascular disease classified
      as VaD or not (VND), according to DSM IV criteria. Neuropsychological
      performances of VaD patients were compared with a group of patients affected by
      probable AD, matched for age, education, and severity of disease. The comparison
      of performances did not reach statistical significance in single
      neuropsychological tasks. The results suggest that neuropsychological examination
      might not clearly differentiate between VaD and AD patients; the similar pattern
      of cognitive impairment is probably indicative of several common pathogenetic
      mechanisms.

PMID- 16287633
TI  - Ultrastructure of rat pup's Purkinje neurons whose mothers were exposed to
      ethanol during pregnancy and lactation.
AB  - This study was intended to investigate the effects of alcohol on the
      ultrastructure of fetal cerebellar Purkinje cells. Twelve adult female rats of
      Sprague-Dawley species were utilized. Control and experiment groups were formed.
      Rats were made pregnant. Rats in experiment group were administered liquid diet
      containing 6% alcohol. Cerebellums of infant rats were taken on 6th, 8th, and
      10th days after birth. For electron microscopy, tissue sections were processed
      and stained with the usual methods. When control and experiment groups were
      compared for electron microscopic investigation, degeneration of mithocondria as
      cristolysis, dilatations of rough endoplasmic reticulum tubuli, and ring-shaped
      appearance of Golgi apparatus unit were determined. In some groups, nuclear
      membrane disintegrated. In cytoplasms of Purkinje cells, multivesicular bodies
      were distinguished. It was determined that liquid diet containing 6% alcohol had
      toxic effects on Purkinje cells and caused ultrastructural signs of degeneration
      in these cells.

PMID- 16287634
TI  - Age and sex differences in neurobehavioral performance: a study of Portuguese
      elementary school children.
AB  - In this study normative data were obtained on measures of IQ, visual/motor, motor
      and memory functions among Portuguese elementary school children. Subjects were
      228 females and 275 males, 8.0 to 11.9 years of age, in grades 2 through 4, who
      participated in a dental study. Performance on all tests improved with increasing
      age. Females performed better in rote verbal learning, psychomotor speed, and
      speed of information processing. Males had higher scores on tests of visual
      learning, visual memory, and fine motor speed and coordination. Nonverbal IQ had
      a significant impact on all tests except motor speed and coordination. Results
      represent an initial attempt to evaluate Portuguese children in educational and
      medical settings.

PMID- 16287635
TI  - Dance movement therapy improves emotional responses and modulates neurohormones
      in adolescents with mild depression.
AB  - This study assessed the profiles of psychological health and changes in
      neurohormones of adolescents with mild depression after 12 weeks of dance
      movement therapy (DMT). Forty middle school seniors (mean age: 16 years old)
      volunteered to participate in this study and were randomly assigned into either a
      dance movement group (n = 20) or a control group (n = 20). All subscale scores of
      psychological distress and global scores decreased significantly after the 12
      weeks in the DMT group. Plasma serotonin concentration increased and dopamine
      concentration decreased in the DMT group. These results suggest that DMT may
      stabilize the sympathetic nervous system. In conclusion, DMT may be effective in
      beneficially modulating concentrations of serotonin and dopamine, and in
      improving psychological distress in adolescents with mild depression.

PMID- 16287636
TI  - Rapid activated sludge respiration inhibition test performed by CO2 producing
      rate using a carbon dioxide sensor.
AB  - The rapid activated sludge inhibition test (rapid ASRI) is one of the promising
      bioassays to evaluate environmental risk to the ecosystem caused by various
      pollutants. To improve the sensitivity and stability of ASRI, the CO2 producing
      rate (CPR) using a carbon dioxide gas sensor was employed to examine the
      respiration activity of activated sludge and to compare it to that by the
      conventional activated sludge respiration inhibition test using oxygen uptake
      rate (OUR) by EC50 values derived from dose response curve. Detection of
      respiratory activity based on CPR has higher reliability and sensitivity than
      that of OUR. It should be noted that the sensitivity of CPR for evaluating
      toxicity is sufficiently high in terms of derived dose response curve of some
      model environmental pollutants and the resultant EC50 values.

PMID- 16287637
TI  - Effect of selected textile effluents on activated sludge nitrification process.
AB  - In this study, a recently developed methodology for the assessment of the
      inhibitory effect on nitrifying biomass was applied to several textile effluents
      from productive processes. Effluents are classified according to the degree of
      inhibition as EC50 (concentration producing 50% nitrification inhibition); the
      investigated textile effluents showed a wide range of EC50 ranging from 20 ml
      gVSS-1 (83 ml l-1) to values above 100 ml gVSS-1 (300 ml l-1) for effluents
      produced by rinsing phases. Taking into account biodegradability and toxicity
      evaluations, most of the effluents showed a good treatability in conventional
      biological wastewater treatment plant. On the other hand three textile effluents
      showed significant toxic effects towards nitrifying biomass. In any case, the
      proposed procedure represents an efficient tool to prevent treatment failures due
      to toxic discharges.

PMID- 16287638
TI  - Prediction of dimethyl disulfide levels from biosolids using statistical
      modeling.
AB  - Two statistical models were used to predict the concentration of dimethyl
      disulfide (DMDS) released from biosolids produced by an advanced wastewater
      treatment plant (WWTP) located in Washington, DC, USA. The plant concentrates
      sludge from primary sedimentation basins in gravity thickeners (GT) and sludge
      from secondary sedimentation basins in dissolved air flotation (DAF) thickeners.
      The thickened sludge is pumped into blending tanks and then fed into centrifuges
      for dewatering. The dewatered sludge is then conditioned with lime before
      trucking out from the plant. DMDS, along with other volatile sulfur and nitrogen
      containing chemicals, is known to contribute to biosolids odors. These models
      identified oxidation/reduction potential (ORP) values of a GT and DAF, the amount
      of sludge dewatered by centrifuges, and the blend ratio between GT thickened
      sludge and DAF thickened sludge in blending tanks as control variables. The
      accuracy of the developed regression models was evaluated by checking the
      adjusted R2 of the regression as well as the signs of coefficients associated
      with each variable. In general, both models explained observed DMDS levels in
      sludge headspace samples. The adjusted R2 value of the regression models 1 and 2
      were 0.79 and 0.77, respectively. Coefficients for each regression model also had
      the correct sign. Using the developed models, plant operators can adjust the
      controllable variables to proactively decrease this odorant. Therefore, these
      models are a useful tool in biosolids management at WWTPs.

PMID- 16287639
TI  - Modeling sulfur dioxide absorption by fine water spray.
AB  - A novel theoretical model was developed to determine the removal efficiency of
      sulfur dioxide using fine water spray. The droplet pH, diameter, S(IV)
      concentration, sulfur dioxide concentration, and liquid-to-gas ratio are found to
      influence the absorption of sulfur dioxide by the fine water spray. The results
      demonstrate that the absorption of sulfur dioxide by the fine water spray
      increases as the droplet diameter falls. The concentration gradient between the
      interface of the gaseous and liquid phases causes the absorption of sulfur
      dioxide by the droplets to increase as the initial S(IV) concentration decreases
      or the sulfur dioxide concentration increases. The results indicate that the
      performance of the fine water spray in removing sulfur dioxide is generally
      improved by reducing the droplet diameter or the initial S(IV) concentration, or
      by increasing the sulfur dioxide concentration, the droplet pH or the liquid-to
      gas ratio. The proposed model reveals the parameters that should be controlled in
      using a fine water spray device and a method for improving its performance in
      removing sulfur dioxide.

PMID- 16287640
TI  - Optimizing cell preparation technique to enhance adsorption capacity of
      pseudomonas putida 5-x to heavy metal ions.
AB  - A heavy metal accumulation bacterium Pseudomonas putida 5-x isolated from
      electroplating effluent was used as biosorbent for heavy metal removal from
      wastewater. In order to compete with physical adsorbent, the optimization of the
      cell preparation technique for further improving its heavy metal adsorption
      capacity was conducted. Experimental results showed that the variation of medium
      compositions and cell growth age, and different cell pre-treating technique would
      result in the variation of the cell surface components and structural, hence the
      variation of adsorption capacity of the cell to heavy metal ions. With optimum
      cell culture conditions and pretreatment technique, the Cu2+ adsorption capacity
      of the cell was obviously increased from 51.2 mg g-1 to 89.6 mg g-1. The
      optimised P. putida 5-x cell could be reused at least five cycles to remove heavy
      metal ions from electroplating effluent with about 95% removal efficiency.

PMID- 16287641
TI  - Accumulation of polycyclic aromatic hydrocarbons from creosote-contaminated soil
      in selected plants and the oligochaete worm Enchytraeus crypticus.
AB  - The accumulation of PAHs from a creosote-contaminated soil was examined in
      laboratory experiments using English ryegrass (Lolium perenne), white clover
      (Trifolium repens) and radish (Raphanus sativus), and the oligochaete worm
      Enchytraeus crypticus. Toxicity to the plants and the worms was assessed, and a
      soil sample mixed with calcined sand was used for accumulation experiments to
      avoid interference from toxicity in the soil. Accumulation of potentially
      carcinogenic PAHs varied among the plants, and there was a linear relation
      between concentrations of PAHs in the soil and in the plants. Correlations
      between values of the biota-soil accumulation factors and octanol-water partition
      coefficients, or water solubility varied among the plants and were rather weak,
      so that lipophilic character or water solubility of the PAHs alone cannot explain
      PAH accumulation. Accumulation of carcinogenic PAHs from the soil, in the
      presence of the other PAHs was greatest for Trifolium repens. PAHs were
      accumulated in the oligochaete worm (Enchytraeus crypticus), and biota-soil
      accumulation factors exceeded those for the plants. It is suggested that site
      specific evaluation of contaminated sites should include not only chemical
      analysis and evaluation of toxicity but also accumulation of contaminants into
      biota such as plants and worms.

PMID- 16287642
TI  - Studies on microbiological degradation of tobacco tar.
AB  - A bacterium, strain MR4, was isolated from tobacco tar-contaminated soil and
      identified as Klebsiella oxytoca based on morphology, physiological and
      biochemical characteristics and phylogenetic analysis of 16S rDNA sequence. The
      organism grew optimally at 34 degrees C and pH 7.0 to 7.5. During growth on
      tobacco tar the isolate produced acid materials, which caused the drop of pH in
      the cultures. GC/MS analysis indicated that the isolate had the ability to
      degrade phenolic compounds, heterocyclic compounds, especially nicotine in
      tobacco tar. The degradation rate of strain MR4 was 75.56% for nicotine, 35.84%
      to 58.16% for hydroxybenzenes and the other aromatic compounds, 29.15% to 65.56%
      for heterocyclics, and 35.17% to 82.59% for hydrocarbons.

PMID- 16287643
TI  - Influence of soil fertilization by sewage sludge on the content of polycyclic
      aromatic hydrocarbons (PAHs) in crops.
AB  - The aim of the present study was an evaluation of the influence of the addition
      of different sewage sludge doses on the uptake of polycyclic aromatic
      hydrocarbons from fertilized soil. Sewage sludge was introduced into the soil in
      the following doses: 30, 75, 150, 300, and 600 Mg/ha. The content of polycyclic
      aromatic hydrocarbons (PAH) was determined by means of HPLC-UV method. The
      addition of increasing doses of sludge into the soil resulted in a gradual
      increase in the amount of the polycyclic aromatic hydrocarbons contained therein.
      During the period of the study, continuous changes in the content of all the
      compounds studied were found in all the experimental variants. Finally, on the
      last day of the study, the highest degree of degradation (73%) of 16 PAHs' sum
      (US EPA) was noted for sludge doses of 30 and 300 Mg/ha. In the case of
      individual PAHs, the change in their content differed and clearly depended on the
      sewage sludge dose. The introduction of sewage sludge into the soil influenced
      the increase of the sum of 16 PAHs in the plants grown in this soil. The
      influence mentioned above depended on the sewage sludge dose and the plant
      species grown, as well as the PAH content in the soil. The evaluation of
      individual PAHs in plants showed an increase in their content with the increase
      of the amount of sewage sludge. A statistically significant increase in their
      content was most often observed for sewage sludge doses above 150 Mg/ha.
      Moreover, it was found that fertilization of the soil with sewage sludge resulted
      in pollution of the plants with PAHs of high molecular weight.

PMID- 16287644
TI  - Residues of DDTs, PAHs and some heavy metals in fish (Tilapia) collected from
      Hong Kong and mainland China.
AB  - Most of the freshwater fish consumed in Hong Kong is imported from the southern
      part of China, although Hong Kong also produces a small amount of freshwater
      fish. The major aim of the present study was to conduct a health risk assessment
      of fish produced from the mainland (purchased from four local markets in Hong
      Kong) compared with those produced from Hong Kong fishponds. Thirty tilapia fish
      (Tilapia mossambicus) were collected from the fishponds at Tam Kon Chau, Nam Sang
      Wai, and Mai Po Nature Reserve (Northwest New Territories of Hong Kong), and four
      local markets (Tai Po, Lok Fu, Sham Shui Po and Cheung Sha Wan wholesale markets)
      in Hong Kong for the analyses of PAHs, DDTs and three toxic metals (cadmium,
      chromium, lead). Tilapia purchased from the markets (with fish supplied from the
      mainland) showed higher concentrations of DDTs and PAHs than those collected from
      Hong Kong fishponds, confirmed that the fishponds in the mainland are more
      polluted due to the rapid socioeconomic growth in the region during the past 20
      years. The tilapia were heavily polluted by Pb, with the highest level (3519 ng g
      1 wet wt.) exceeded the EUROPA guideline (400 ng g-1 wet wt.) 8 times, and Cr
      with 36% of the samples exceeded the China guideline of 500 ng g-1 wet wt. for
      human consumption. The coastal Chinese populations which consume larger
      quantities of fish may be at risk. Tilapia collected from the Mai Po Nature
      Reserve contained the highest level of Cr, which may also impose adverse effects
      on water birds, including the endangered species that frequently visiting the
      site for food and shelter.

PMID- 16287645
TI  - Introduction to competition between continuous cultures of Phaeodactylum
      tricornutum and Dunaliella tertiolecta.
AB  - When the diatom, Phaeodactylum tricornutum, and the microalga, Dunaliella
      tertiolecta, are cultured together in a chemostat at dilution factors of
      approximately 0.5 day-1, the diatom develops the higher population density. At
      dilution factors above 1.2 day-1 the inability of the diatom to assimilate
      nutrient as fast as it flows into the chemostat results in the microalga
      generating the larger population. This change in population densities is
      accompanied by an increase in the chlorophyll content of the diatom and a
      decrease in the chlorophyll content of the microalga. Two species of
      phytoplankton can coexist when they compete for nutrient in a chemostat providing
      they do not otherwise interact. When the species do interact coexistence in a
      stable steady state is possible providing intraspecies interactions exceed the
      interactions between the species. Both species adjust their consumption to
      minimise the concentration of nutrient in the chemostat and their growth is
      modified to match the dilution factor of the flow.

PMID- 16287648
TI  - Does the acoustic waveform mirror the voice?
AB  - Over recent decades, much effort has been invested in the search for acoustic
      correlates of vocal function and dysfunction. The convenience of non-invasive
      voice measurements has been a major incentive for this effort. The acoustic
      signal is a rich but also very diversified source of information. Computer
      literacy and technical curiosity in the voice care and voice performance
      communities are now higher than ever, and tools for voice analysis are
      proliferating. On such a busy scene, a review may be useful of some basic
      principles for what we can and cannot hope to determine from non-invasive
      acoustic analysis. One way of doing this is to consider communication by voice as
      though it were engineered, with layered protocols. This results in a scheme for
      systematizing the many sources of variation that are present in the acoustic
      signal, that can complement other strategies for extracting information.

PMID- 16287649
TI  - Discussant response to 'Does the acoustic waveform mirror the voice?'.
AB  - The acoustic waveform that reaches the two ears of a listener can convey the
      intended message. Over the telephone, this waveform is the only source of
      information from the speaker, since the listener is out of visual contact;
      indeed, in this situation the acoustic waveform itself is restricted in its
      frequency content. Whilst the listener can infer much about the speaker from the
      acoustic waveform, including the speaker's age, gender, nationality, dialect, and
      emotional state, the issue under consideration here is the extent to which
      quantitative analysis of the acoustic waveform can provide useful information
      about a speaker's voice. This paper was presented as an Invited Discussant
      Response, at the Pan-European Voice Conference (PEVOC6) in London, to the
      question posed in Ternstrom's Invited Keynote Lecture 1: Does the acoustic
      waveform mirror the voice?

PMID- 16287651
TI  - Voice disorders and gastroesophageal reflux.
AB  - Gastroesophageal reflux (GER) can cause serious voice problems and
      laryngopharyngeal disorders influencing the patient's quality of life. Forty
      three patients with suspected laryngopharyngeal reflux (LPR) were included into a
      prospective study. The diagnosis was made on the basis of the patient's history,
      the videoendolaryngoscopy, the oesophago-gastroscopy and the biopsy of the
      oesophageal mucosa. All the LPR patients were treated with esomeprasol for eight
      weeks. An acoustic analysis of the vowel /a/ samples was performed in the LPR
      group before and after the treatment. Thirty-six patients with vocal fold polyps
      served as the control group for a subjective estimation of the voice problems.
      All the patients from both groups subjectively evaluated their voice problems
      using the Voice Handicap Index (VHI) questionnaire. The results of VHI showed
      that the severity of the voice problems of the patients with LPR could be
      compared to that experienced by the patients with vocal fold polyps.
      Videoendolaryngoscopy and history proved LPR in all 43 patients. Oesophago
      gastroscopy combined with the histopathological examination of the oesophageal
      biopsy specimens detected signs of possible GER in 38 patients (88%). The results
      of the videoendolaryngoscopy combined with a subjective and objective voice
      assessment, performed before and after treatment with a proton-pump inhibitor,
      showed a significant improvement in most of the studied parameters by the end of
      the therapy. In the diagnostics of LPR, the patient's history and
      videoendolaryngoscopy demonstrated to be superior to oesophago-gastroscopy.
      Videoendolaryngoscopic assessment of the laryngeal mucosa, and oesophago
      gastroscopy supplemented with a biopsy of the oesophageal mucosa, showed to be a
      convenient diagnostic method when GER and LPR were suspected. Esomeprasol proved
      to be very effective in the treatment of LPR. LPR should not be overlooked in the
      treatment of dysphonic patients.

PMID- 16287650
TI  - Voice after supracricoid laryngectomy: subjective, objective and self-assessment
      data.
AB  - Supracricoid laryngectomy (SCL) is an efficient surgical procedure for the
      treatment of selected laryngeal carcinoma, presently being performed not only in
      Europe but also in North America. The functional goals of the technique are voice
      and swallowing without a permanent tracheostoma. Perceptual and acoustic voice
      characteristics after SCL have been reported by different authors, but self
      assessment data together with subjective and objective data have only been
      reported for a small number of subjects. Twenty male subjects, with a mean age of
      71 years (range: 51-82 years) who underwent a SCL at least one year before our
      observation, were included in the study. Each subject underwent a flexible
      laryngoscopy and his voice was perceptually rated using the GRBAS scale.
      Objective examination included: maximum phonation time (MPT), voice spectrograms
      and syllable diadochokinesis on a single breath. Finally, each subject assessed
      his own voice using the Voice Handicap Index (VHI). The mean values of the GRBAS
      scale were respectively 2.4, 2.6, 2.4, 0.8, 0.5, 0.8. Mean MPT was 7.5 s, while
      for voice spectrograms the mean value of the Yanagihara scale was 3.7. Mean
      syllable diadochokinesis appeared as 3.3 syllables/s. Mean value of the VHI was
      29.9. Subjective and objective data show a severely dysphonic voice after SCL;
      self-assessment data, on the contrary, reveal only moderate functional and
      emotional consequences. While perceptual, aerodynamic and acoustic data are in
      line with previous reports, self-assessment data were less severe in our subjects
      compared to what appears in the literature. It is concluded that self-assessment
      explores a different dimension of the patient's voice and that even if a severe
      dysphonia is present the consequences on everyday oral communication are only
      moderate.

PMID- 16287652
TI  - Comparative histochemical aspects of mammalian thyroarytenoid musculature.
AB  - A survey is given of histological and histochemical aspects of mammalian
      thyroarytenoid musculature of several animal species. Purpose of the study is to
      find out in what respect the possibility of differentiated and prolonged sound
      production can be found back in the histological and histochemical properties of
      mammalian thyroarytenoid musculature. The findings are compared to the results of
      previous studies of thyroarytenoid musculature in man (Kersing and Jennekens,
      2004). The presence of type I fibres seems to be crucial.

PMID- 16287653
TI  - Towards an understanding of speech and song perception.
AB  - The human singing voice plays an important role in music of all societies. It is
      an extremely flexible instrument and is capable of producing a tremendous range
      of sounds. As such, the human voice can be hard to classify and poses a major
      challenge for automatic audio discrimination and classification systems.
      Speech/song discrimination is an implicit goal of speech/music discrimination,
      where a division is sought between speech and song, such that the singing voice
      can be grouped together with other musical instruments in the same category.
      However, the division between speech and song is unclear and even human attempts
      at speech/song discrimination can be highly subjective and open to discussion. In
      this paper we present the results of a test that was designed to investigate
      differences in auditory perception for speech and song. Twenty-four subjects were
      instructed to attend to either the words or pitch, or both words and pitch of
      context-free spoken and sung phrases. After presentation of each phrase, subjects
      were asked to either type the words that they recalled, or select the correct
      pitch contour from a choice of four graphical representations, or do both,
      depending on the task specified before presentation of the phrase. The results of
      the experiment show a decrease in the amount of linguistic information retained
      by subjects for sung phrases and also a decrease in accuracy of response for the
      sung phrases when subjects attended to both words and pitch instead of words or
      pitch alone.

PMID- 16287654
TI  - Objective analysis of the singing voice as a training aid.
AB  - A new tool for robust tracking of fundamental frequency is proposed, along with
      an objective measure of main singing voice parameters, such as vibrato rate,
      vibrato extent, and vocal intonation. High-resolution Power Spectral Density
      estimation is implemented, based on AutoRegressive models of suitable order,
      allowing reliable formant tracking also in vocalizations characterized by highly
      varying values. The proposed techniques are applied to about 1000 vocalizations,
      coming from both professional and non-professional singers, and show better
      performance as compared to classical Fourier-based approaches. If properly
      implemented, and with a user-friendly interface, the new tool would allow real
      time analysis of singing voice. Hence, it could be of help in giving non
      professional singers and singing teachers reliable measures of possible
      improvements during and after training.

PMID- 16287655
TI  - Electrolaryngographically derived voice source changes of child and adolescent
      singers.
AB  - Children are the most likely demographic group to undertake regular singing or
      singing training, but to date there has been little quantitative research into
      the voice production of children. The authors used closed quotient (CQ)
      measurements to analyse the singing voices of over 200 male and female, trained
      and untrained singers aged 8-18 years for differences in voice source according
      to sex, vocal training and age. Results indicated that the voice source
      production of subjects could be clearly divided into groups according to age, sex
      and the level of vocal training received. It was concluded that the process of
      training a young voice has a quantifiable effect upon the voice source. It was
      also concluded that sex differences result in significant differences in the
      voice source of child and adolescent singers.

PMID- 16287656
TI  - An exploratory baseline study of boy chorister vocal behaviour and development in
      an intensive professional context.
AB  - Currently, there is no existing published empirical longitudinal data on the
      singing behaviours and development of choristers who perform in UK cathedrals and
      major chapels. Longitudinal group data is needed to provide a baseline against
      which individual chorister development can be mapped. The choristers perform to a
      professional standard on a daily basis, usually with linked rehearsals, whilst
      also following a full school curriculum. The impact of this intensive schedule in
      relation to current vocal behaviour, health and future development requires
      investigation. Furthermore, it is also necessary to understand the relationship
      between the requirements of chorister singing behaviour and adolescent voice
      change. The paper will report the initial findings of a new longitudinal
      chorister study, based in one of London's cathedrals. Singing and vocal
      behaviours are being profiled on a six-monthly basis using data from a specially
      designed acoustic and behavioural instrument. The information obtained will
      enable us to understand better the effects of such training and performance on
      underlying vocal behaviour and vocal health. The findings will also have
      implications for singing teachers and choral directors in relation to particular
      methods of vocal education and rehearsal.

PMID- 16287657
TI  - Manuel Garcia Jr: a clear-sighted observer of human voice production.
AB  - Before Garcia, only a few notions of vocal production can be found in earlier
      singing treatises. In those days the authors wrote mainly upon the art of
      ornamentation and the rules of good language utterance. In the beginning of the
      19th century, a radical change occurred with the development of scientific
      experiments. Several doctors or physicists drew up theories on human voice
      production, which were similar to those of sound production in woodwind
      instruments: flute, reed, or membranous lips. Yet, as the experiments on living
      human beings were impossible, the true nature of the vocal source remained under
      discussion. In addition, specific questions arose in regard to singing: Are the
      different registers produced by different vibrating sources or are they due to
      modifications of a single vibrating system? What are the reasons for a variation
      in loudness and in pitch, and how are the variations of voice timbre produced?
      Facing the contradictory opinions of the most famous scientists, Manuel Garcia Jr
      showed an astonishing insight as early as 1840, when he wrote his first 'Memoire
      sur la voix humaine' presented to the Academie des Sciences de Paris. Being
      altogether an anatomist, a singer, and a great pedagogue, he could accurately
      observe the physiological phenomena of human voice in the right way. As the first
      user of the laryngoscope, he wrote a second paper presented at the Royal Society
      of London, in 1855, in which he confirmed his previous views. All along the
      different issues of his well-known singing method, we may see the lucidity and
      the improvements of Garcia's ideas. The only concession he made to the singers is
      related to the famous 'Fausset-tete' register, an unfortunate word that was bound
      to induce confusion later.

PMID- 16287658
TI  - Vocal symptoms among teachers with and without voice education.
AB  - This study investigates the amount of voice training received by teachers in
      Finland and compares the incidence of vocal symptoms among teachers with shorter,
      longer or no vocal education. Participating were 124 primary, secondary and upper
      secondary school teachers; 63% of the teachers had received no vocal training,
      15% had received short-term and 22% longer-term training. The incidence of
      symptoms was lowest in teachers with long-term training and highest in teachers
      with short-term training. The differences were non-significant among all teachers
      and females, but significant among males. Speech training seems to protect male
      teachers from vocal problems better than female teachers. Short-term training may
      lead to increased awareness of vocal symptoms, which can be helpful in voice
      protection.

PMID- 16287659
TI  - Phonetic considerations in the design of voice assessment material.
AB  - A read text is commonly used in voice clinics for auditory perceptual evaluation
      of dysphonic voices and acoustic analysis. This paper examines the phonetic make
      up of texts in several European languages to investigate their comparability in
      the frameworks of international, multi-lingual clinical studies, and the need for
      outcome measures in evidence-based practice. The preliminary work described
      investigates the complex notion of phonetic balancing. It shows that, despite
      very different phoneme inventories, certain similarities of sound-type usage
      appear cross-linguistically. Although this high level analysis is of interest and
      of potential practical use, because of linguistic and speaker-dependent
      contextual variation, more fine-grained phonetic and acoustic analyses are
      needed.

PMID- 16287660
TI  - Tone choice and voice quality of dispreferred turns in the English of Finns.
AB  - Authentic Finnish-English speech data was collected as part of an English
      conversation class in a Finnish college. Intonation was coded utilizing the
      framework involving 'tone', 'key' and 'termination'. A categorization of voice
      quality was chosen (e.g., 'modal voice', 'creak', 'breathy', and 'tense'). The
      tempo of speech was transcribed with such descriptors as, e.g., 'fast' and
      'slow'. The majority of dispreferred turns in the data represented mitigated
      disagreement, with structural complexity (involving, e.g., wordiness). The p tone
      was predominant: a low/mid key often accompanied mitigated disagreement. The r
      and r+ tones were virtually absent in the mitigated dispreferred turns. Instead,
      the speakers often used a very lax/breathy voice quality and a slow/decelerating
      tempo, often resulting in creak near a transition relevant place.

PMID- 16287661
TI  - Health and voice quality in smokers: an exploratory investigation.
AB  - Thirty-two adults (20 smokers and 12 non-smokers) were examined to determine the
      effects of cigarette smoking on health (diseases and larynx histology), on
      fundamental frequency (regularity and jitter) and stress level. The examination
      consisted of nasovideostroboscopy analysis, history case, electrolaryngography
      assessment for different task performance and self-assessment of stress. Although
      not statistically different, results indicate that smokers in comparison to non
      smokers show: 1) slightly more health problems; 2) histological larynx changes;
      3) a higher level of stress; 4) a lower mean F0 for all speech tasks. A
      statistically significant difference for percentage jitter was found according to
      voice status for: 1) vowel [a] (the group with voice problems show higher levels
      of jitter than both groups without voice problems); 2) vowel [i] (the smokers
      with voice problems show higher levels of jitter than the smokers without voice
      problems).

PMID- 16287663
TI  - Some current aspects on publication, citation and impact factor for Journal of
      Rehabilitation Medicine.

PMID- 16287662
TI  - Medical assessment of adolescent girls with eating disorders: an evaluation of
      symptoms and signs of starvation.
AB  - AIM: To investigate the prevalence of symptoms and signs related to starvation at
      the initial examination of adolescent girls with eating disorders (ED). METHODS:
      Two hundred and eleven girls with eating disorders recruited for a multicentre
      research and evaluation programme of six specialist eating disorder services in
      Sweden have been studied. The presence or absence of 12 symptoms, reported by the
      patients, and 16 signs, observed by the examiners, were registered and related to
      body weight. RESULTS: Eleven observed signs--loss of subcutaneous fat, loss of
      muscle mass, loss of muscular force, dry and scaly skin, brittle nails, dry and
      brittle hair, lanugo hair, resting pulse <60, systolic blood pressure <110,
      peripheral hypothermia, and peripheral cyanosis--were related to body weight
      expressed in standard deviation scores (SDS). When the number of observed signs
      for each patient was calculated, there was a strong relationship with weight. The
      odds ratio for having more than two signs was 4.35 (95% CI 2.67-7.04; p = 2.8 x
      10(-9) for every one-unit change in weight SDS. Of the symptoms reported by the
      patients, only three were related to weight. When the number of reported symptoms
      for each patient was calculated, a relationship with weight was not observed.
      CONCLUSION: In adolescent girls with ED, physical signs observed at medical
      examination can be related to weight. However, reported symptoms are poorly
      related to weight and may be influenced by other factors. The finding emphasizes
      the importance of medical assessment at presentation of patients with ED.

PMID- 16287664
TI  - Contemporary measurement techniques for rehabilitation outcomes assessment.
AB  - In this article, we review the limitations of traditional rehabilitation
      functional outcome instruments currently in use within the rehabilitation field
      to assess Activity and Participation domains as defined by the International
      Classification of Function, Disability, and Health. These include a narrow scope
      of functional outcomes, data incompatibility across instruments, and the
      precision vs feasibility dilemma. Following this, we illustrate how contemporary
      measurement techniques, such as item response theory methods combined with
      computer adaptive testing methodology, can be applied in rehabilitation to design
      functional outcome instruments that are comprehensive in scope, accurate, allow
      for compatibility across instruments, and are sensitive to clinically important
      change without sacrificing their feasibility. Finally, we present some of the
      pressing challenges that need to be overcome to provide effective dissemination
      and training assistance to ensure that current and future generations of
      rehabilitation professionals are familiar with and skilled in the application of
      contemporary outcomes measurement.

PMID- 16287666
TI  - Participation after stroke compared to normal aging.
AB  - OBJECTIVE: To examine the reduction in participation of people who have had a
      stroke compared with healthy people with normal aging. DESIGN: Participation of
      people who had a stroke was compared with participation of healthy subjects.
      SUBJECTS/PATIENTS: Forty-six people who had a stroke for 2-4 years and 46 healthy
      participants matched on age, sex and living environment. MEASUREMENTS:
      Participation was estimated with the Assessment of Life Habits (LIFE-H). The LIFE
      H (short version 2.1) is composed of 58 daily activities and social roles
      associated to the 12 categories of the Disability Creation Process model. The
      LIFE-H gives separate scores for each category, for 2 main subsections "Daily
      activities" and "Social roles" and a total score. RESULTS: Scores of healthy
      subjects did not reach the maximum value (9/9) of the LIFE-H, their mean scores
      varying from 6.3 to 8.6, according to the categories. These scores are higher
      than of the participants with stroke for all categories (scores varying from 3.9
      to 6.5; p-values from 0.002 to <0.001), except the interpersonal relationships
      category (score of 7.8 vs 8.0) where no difference was found (p=0.49). The
      disruption in participation after stroke varies according to the categories of
      the LIFE-H, but is more important in the daily activities categories. CONCLUSION:
      The comparison of the scores obtained by the 2 groups suggests that a part of the
      reduction in participation in daily activities and social roles after stroke is
      attributable to normal aging and not entirely to the stroke itself. It helps to
      focus interventions on activities and roles disruption domains that are really
      attributable to stroke.

PMID- 16287665
TI  - Differential item functioning of the Functional Independence Measure in higher
      performing neurological patients.
AB  - OBJECTIVE: When comparing outcomes of the Functional Independence Measure (FIM )
      between patient groups, item characteristics of the FIM should be consistent
      across groups. The purpose of this study was to compare item difficulty of the
      FIM in 3 patient groups with neurological disorders. SUBJECTS: Patients with
      stroke (n=295), multiple sclerosis (n=150), and traumatic brain injury (n=88).
      METHODS: FIM scores were administered in each group. The FIM consists of a motor
      domain (13 items) and a cognitive domain (5 items). Rasch rating scale analysis
      was performed to investigate differences in item difficulty (differential item
      functioning) between groups. RESULTS: Answering categories of the FIM items were
      reduced to 3 (from the original 7) because of disordered thresholds and low
      answering frequencies. Two items of the motor domain ("bladder" and "bowel") did
      not fit the Rasch model. For 7 out of the 11 fitting motor items, item
      difficulties were different between groups (i.e. showed differential item
      functioning). All cognitive items fitted the Rasch model, and 4 out of 5
      cognitive items showed differential item functioning. CONCLUSION: Differential
      item functioning is present in several items of both the motor and cognitive
      domain of the FIM. Adjustments for differential item functioning may be required
      when FIMdata will be compared between groups or will be used in a pooled data
      analysis.

PMID- 16287667
TI  - Erectile dysfunction in spinal cord injury: a cost-utility analysis.
AB  - BACKGROUND: There is a high incidence of erectile dysfunction after spinal cord
      injury. This can have a profound effect on quality of life. Treatment options for
      erectile dysfunction include sildenafil, intracavernous injections of
      papaverine/alprostadil (Caverject), alprostadil/papaverine/phentolamine ("Triple
      Mix"), transurethral suppository (MUSE), surgically implanted prosthetic device
      and vacuum erection devices. However, physical impairments and accessibility may
      preclude patient self-utilization of non-oral treatments. METHODS: The costs and
      utilities of oral and non-oral erectile dysfunction treatments in a spinal cord
      injury population were examined in a cost-utility analysis conducted from a
      government payer perspective. Subjects with spinal cord injury (n=59) reported
      health preferences using the standard gamble technique. RESULTS: There was a
      higher health preference for oral therapy. The cost-effectiveness results
      indicated that sildenafil was the dominant economic strategy when compared with
      surgically implanted prosthetic devices, MUSE(R) and Caverject. The incremental
      cost-utility ratios comparing sildenafil with triple mix and vacuum erection
      devices favoured sildenafil, with ratios less than CAN$20,000 per quality
      adjusted life year gained. CONCLUSION: Based on this study, we conclude that
      sildenafil is a cost-effective treatment for erectile dysfunction in the spinal
      cord injury population.

PMID- 16287668
TI  - Predictors of return to work in patients sick listed for sub-acute low back pain:
      a 12-month follow-up study.
AB  - OBJECTIVE: To investigate whether personal and work-related factors, physical
      performance and back-specific questionnaires predict return to work. A
      prospective study identifying prognostic factors for return to work. SUBJECTS:
      Ninety-three patients sick-listed for 8-12 weeks for non-specific sub-acute low
      back pain included in a randomized controlled trial. METHODS: Patients were
      examined with regard to demographic variables, a battery of back-specific
      questionnaires and physical tests before entering a randomized controlled trial.
      A stepwise backward Cox regression model was established to identify the most
      powerful predictors. RESULTS: During follow-up 78.5% of the patients have
      returned to full-time work. Fear-avoidance beliefs for work (relative risk (RR)
      for 1 SD change 0.49; 95% confidence interval (CI) 0.38-0.64), disability (RR
      1.39, 95% CI 1.02-1.88) and cardiovascular fitness (RR 1.42, 95% CI 1.12-1.79)
      were identified as the best predictors for return to work. The prevalence of
      correct predictions was 69.3%. CONCLUSION: The predictors identified in the
      present study may reflect personal risk factors in a patient who gets acute low
      back pain. On the other hand, they may support that fear of pain and injury may
      be more disabling than pain itself, and that deconditioning is a result of
      altered behaviour reflecting attitudes towards low back pain in society, and
      information and advice given in primary healthcare.

PMID- 16287670
TI  - Gender comparisons of function-related dependence, pain and insecurity in
      geriatric rehabilitation.
AB  - OBJECTIVE: To evaluate possible gender differences regarding the effect of
      intervention in geriatric rehabilitation, expressed in terms of change in
      function-related dependence, pain and insecurity. DESIGN: Comparative study.
      PARTICIPANTS: A total of 110 women and 44 men undergoing geriatric
      rehabilitation. METHODS: Performance-based assessments with use of the General
      Motor Function assessment scale. Non-parametric statistics were mainly used.
      RESULTS: The women showed higher degrees of function-related dependence, pain and
      insecurity on admission than the men. Both women and men displayed significant
      improvement in all 3 variables during the rehabilitation period. However, the
      positive changes regarding pain and insecurity were according to the analyses of
      systematic group changes, at a low degree among the men, probably because of the
      low levels on admission. Gender comparisons of proportions with positive
      intervention outcome indicated that a significantly larger proportion of the
      women showed a positive treatment effect after intervention, with a difference in
      recovery of 19% in dependence, 23% in pain and 33% in insecurity (p<0.05).
      CONCLUSIONS: Gender differences in disability, with higher degrees of function
      related dependence, pain and insecurity among women on admission for geriatric
      rehabilitation, can be diminished during the rehabilitation period. These
      promising results may have relevance for the public health of the elderly
      population.

PMID- 16287669
TI  - Ice and pulsed electromagnetic field to reduce pain and swelling after distal
      radius fractures.
AB  - OBJECTIVE: To examine the relative effectiveness of ice therapy and/or pulsed
      electromagnetic field in reducing pain and swelling after the immobilization
      period following a distal radius fracture. METHODS: A total of 83 subjects were
      randomly allocated to receive 30 minutes of either ice plus pulsed
      electromagnetic field (group A); ice plus sham pulsed electromagnetic field
      (group B); pulsed electromagnetic field alone (group C), or sham pulsed
      electromagnetic field treatment for 5 consecutive days (group D). All subjects
      received a standard home exercise programme. A visual analogue scale was used for
      recording pain; volumetric displacement for measuring the swelling of the
      forearm; and a hand-held goniometer for measuring the range of wrist motions
      before treatment on days 1, 3 and 5. RESULTS: At day 5, a significantly greater
      cumulative reduction in the visual analogue scores as well as ulnar deviation
      range of motion was found in group A than the other 3 groups. For volumetric
      measurement and pronation, participants in group A performed better than subjects
      in group D but not those in group B. CONCLUSION: The addition of pulsed
      electromagnetic field to ice therapy produces better overall treatment outcomes
      than ice alone, or pulsed electromagnetic field alone in pain reduction and range
      of joint motion in ulnar deviation and flexion for a distal radius fracture after
      an immobilization period of 6 weeks.

PMID- 16287671
TI  - ABility to rise independently from a chair during 6-month follow-up after
      unilateral and bilateral total knee replacement.
AB  - OBJECTIVE: The purpose of this study was to compare extensor mechanism function
      using a sit-to-stand test in patients undergoing uni- and bilateral total knee
      replacement, with a 6-month follow-up. DESIGN: Prospective controlled study.
      PATIENTS: The series included 72 patients with total knee replacement (unilateral
      32 patients, bilateral 40 patients). METHODS: All patients were evaluated pre
      operatively by the physiotherapist and then at 2-weekly intervals during the
      postoperative 6 months using Hospital for Special Surgery knee score, and range
      of motion. Extensor mechanism function was evaluated at the same time points
      using a sit-to-stand test. RESULTS: At the end of study, there was no difference
      between the groups in their knee range of motion and Hospital for Special Surgery
      scores (p>0.05). There was a significant difference between the groups in their
      chair rising ability (p<0.05). At 2 weeks, 22% of patients in the group with
      unilateral total knee replacement and 20% of patients in the group with bilateral
      total knee replacement could rise independently. However, there was significant
      difference in favour of unilateral total knee replacement at 4, 6, 8 and 10
      weeks. At 10 weeks, all patients in the group with unilateral total knee
      replacement and at 6 months all patients in the group with bilateral total knee
      replacement could rise independently. CONCLUSION: We conclude that patients with
      unilateral total knee replacement gain independence earlier than patients with
      bilateral total knee replacement. However, for patients with bilateral total knee
      replacement eventually to gain independence, they should be prepared for a longer
      rehabilitation programme.

PMID- 16287672
TI  - Effect of financial compensation on vocational rehabilitation.
AB  - OBJECTIVE: To examine how financial compensation affects the outcome of
      vocational rehabilitation. DESIGN: A registry-based follow-up study. SUBJECTS: A
      total of 1397 rehabilitees discharged from the 5 local rehabilitation agencies in
      Aarhus County, Denmark from 1 July 2000 to 31 December 2001. METHODS: At
      submission demographic data was obtained as well as data on financial
      compensation, i.e. compensation for industrial injury, indemnity for off-duty
      injury and application for disability pension. Rehabilitation outcomes were
      recorded at discharge. Renouncing further attempts at rehabilitation was defined
      as a negative outcome; education, further rehabilitation or return-to-work on
      normal or less demanding terms were defined as a positive outcome. Rehabilitees
      with and without financial compensation were compared. RESULTS: Rehabilitees with
      involvement of financial compensation had an increased risk of a negative outcome
      compared with those without involvement of financial compensation. Adjustment for
      potential confounders did not change the association between financial
      compensation and negative outcome. The risk of a negative outcome rose with
      increasing age, with less than 1 year of labour market experience and with rented
      housing. Previous occupation as a skilled worker reduced the risk. CONCLUSION:
      Financial compensation was associated with an increased risk of a negative
      vocational rehabilitation outcome.

PMID- 16287675
TI  - A perspective on medical infrared imaging.
AB  - Since the early days of thermography in the 1950s, image processing techniques,
      sensitivity of thermal sensors and spatial resolution have progressed greatly,
      holding out fresh promise for infrared (IR) imaging techniques. Applications in
      civil, industrial and healthcare fields are thus reaching a high level of
      technical performance. The relationship between body temperature and disease was
      documented since 400 bc. In many diseases there are variations in blood flow, and
      these in turn affect the skin temperature. IR imaging offers a useful and non
      invasive approach to the diagnosis and treatment (as therapeutic aids) of many
      disorders, in particular in the areas of rheumatology, dermatology, orthopaedics
      and circulatory abnormalities. This paper reviews many usages (and hence the
      limitations) of thermography in biomedical fields.

PMID- 16287676
TI  - Electrical potentials derived from articular cartilage: the significance of
      polarization potentials.
AB  - Changes of electrical potentials in cartilage tissue under mechanical compression
      have been detected in several studies. As polarization potentials are known to
      occur at the interface between metals and electrolytes, the question remains open
      whether the measured electrical potentials in relation to mechanical compression
      are interfered with polarization potentials. Using a porcine model, whole knee
      joints were explanted and exposed to uniaxial loading of up to 250 N. Under
      similar conditions, a tube filled with normal saline was prepared with three gold
      plated electrodes. Changes of voltage derived from the electrodes placed in
      normal saline could be detected only when the force was applied instantly by a
      hydraulically controlled pump. In comparison, mechanically induced electrical
      potentials could be derived from cartilage tissue when exposed to both sudden
      force and force induced more slowly by an electric engine. While the electrical
      response derived from cartilage tissue correlated with the extent of the applied
      force, there was no such correlation between the potential changes from normal
      saline and the applied mechanical force. In conclusion, polarization potentials
      derived from metal electrodes in contact with electrolyte solution are pressure
      dependent. However, those electrical potential changes obtained from the
      cartilage tissue under compressive force revealed no obvious influence by
      polarization potentials.

PMID- 16287677
TI  - Micromachined oxygen gas sensors for microscopic energy consumption measurement
      systems.
AB  - Although the indirect calorimeter is a useful tool, its size and expense mean
      that it is seldom used in hospitals. Furthermore, its flow-through measurement
      technique dilutes respiratory variations, so they can only be detected with some
      form of high-precision instrumentation. This study employs MEMS techniques to
      develop an oxygen sensor as one part of a microscopic energy consumption
      measurement system, which measures respiration dynamics in a real time manner.
      The oxygen sensor comprises a polysilicon resistor and a Li-doped (2 wt%) tin
      oxide sensing film attached to a thermally isolated silicon-nitride membrane. The
      power consumption of the sensor is less than 25 mW at an operating temperature of
      150 degrees C. Furthermore, it measures oxygen concentrations between 25 and 85%
      with a linear output response. These characteristics render the proposed sensor
      suitable for use within a microscopic energy consumption measurement system in
      either hospital or homecare environments.

PMID- 16287679
TI  - Performance improvement of the SPIHT coder based on statistics of medical
      ultrasound images in the wavelet domain.
AB  - This paper proposes some modifications to the state-of-the-art Set Partitioning
      In Hierarchical Trees (SPIHT) image coder based on statistical analysis of the
      wavelet coefficients across various subbands and scales, in a medical ultrasound
      (US) image. The original SPIHT algorithm codes all the subbands with same
      precision irrespective of their significance, whereas the modified algorithm
      processes significant subbands with more precision and ignores the least
      significant subbands. The statistical analysis shows that most of the image
      energy in ultrasound images lies in the coefficients of vertical detail subbands
      while diagonal subbands contribute negligibly towards total image energy. Based
      on these statistical observations, this work presents a new modified SPIHT
      algorithm, which codes the vertical subbands with more precision while neglecting
      the diagonal subbands. This modification speeds up the coding/decoding process as
      well as improving the quality of the reconstructed medical image at low bit
      rates. The experimental results show that the proposed method outperforms the
      original SPIHT on average by 1.4 dB at the matching bit rates when tested on a
      series of medical ultrasound images. Further, the proposed algorithm needs 33%
      less memory as compared to the original SPIHT algorithm.

PMID- 16287678
TI  - An algorithm for synchronization of in vivo electroporation with ECG.
AB  - The combined treatment of tumours in which delivery of a chemotherapeutic agent
      is followed by high voltage electroporation pulses has been termed
      electrochemotherapy. The electrochemotherapy of tumours located relatively close
      to the heart muscle can lead to fibrillation of the heart, especially if
      electroporation pulses are delivered in the vulnerable period of the heart or in
      coincidence with heart arrhythmias. We built an electroporation pulse delivery
      algorithm that enables safer use of electrochemotherapy. The algorithm is
      designed to deliver pulses outside the vulnerable period and to prevent pulses
      from being generated in the presence of heart arrhythmias. We evaluated the
      algorithm's performance using records of the Long-Term ST Database, thus
      simulating real-world conditions. The results of the evaluation, a sensitivity of
      91.751%, a positive predictivity of 100.000% and a delivery error rate of 8.268%
      for electroporation pulse delivery (medians), suggest that the algorithm is
      accurate and appropriate for application in electrochemotherapy of tumours
      regardless of tumour location.

PMID- 16287680
TI  - World-first implantable aortic valvo-pump (IAVP) with sufficient haemodynamic
      capacity.
AB  - For better anatomic and physiologic fitting, a novel implantable aortic valvo
      pump (IAVP) has been developed. A valvo-pump is a micro axial flow impeller pump,
      which has the same dimensions and function, as well as the same location, of a
      valve. Therefore, IAVP needs no inlet and outlet tubes, no additional anatomic
      occupation, and has less physiologic disturbance to natural circulation compared
      with the traditional bypass left ventricular assist device (LVAD). The device has
      a stator and a rotor. The stator consists of a motor coil with an iron core and
      an outflow guide vane; the rotor includes driven magnets and impeller. There is
      neither bearing nor strut in both the pump and the motor. In order to reduce the
      attractive force between the rotor and the stator, so as to enhance the
      durability of the performance, the rotor magnets were minimized without reducing
      the driving torque and efficiency of the motor. The impeller vane was designed
      according to a three-dimensional and analytical method, for preventing stasis and
      turbulence. The largest outer diameter is 24.7 mm and the length at this point is
      12.4 mm. The total weight is 40 g (including the rotor of 11 g). The consumed
      power is 7 W (14 V x 0.5 A) at 15 000 rpm. This rotating speed stays unchanged
      during haemodynamic testing together with a pulsatile centrifugal pump, which
      imitates a failing ventricle. The maximal flow cross IAVP reaches over 10 l min(
      1) and the pressure head at 0 l min(-1) can be as large as 80 mmHg. At flow rate
      of 4 - 8 l min(-1), IAVP enlarges the flow c. 1 l min(-1) and meanwhile increases
      the pressure about 10 mmHg. The pressure pulsatility generated by the pulsatile
      centrifugal pump remains 40 mmHg after passing IAVP. By first animal experimental
      trial the device was sewed in aortic position of an 80 kg pig without harm to
      adjacent tissue and organs. IAVP promises to be a viable alternative to natural
      donor heart for heart transplantation in the future.

PMID- 16287683
TI  - Enteroviruses as agents of emerging infectious diseases.
AB  - Although the enteroviruses as a group are ubiquitous and not normally considered
      as "emerging pathogens," the many different serotypes circulate at different
      frequencies in any given year and the prevalence of a given serotype may
      fluctuate wildly from year to year. As a result, several enterovirus serotypes
      have been associated with the emergence of specific diseases (for example,
      pandemic acute hemorrhagic conjunctivitis) and specific serotypes have emerged to
      cause outbreaks of major public health concern. Enterovirus 71 is a recognized
      cause of epidemic severe central nervous system disease in Southeast Asia. Acute
      hemorrhagic conjunctivitis was a newly described disease in the 1970s associated
      with emergence of enterovirus 70 and coxsackievirus A24 variant. In addition, the
      impending eradication of poliovirus and some of the challenges currently faced by
      the eradication program present the possibility that poliomyelitis could emerge
      in the posteradication era. These links between enterovirus infections and
      emerging diseases are reviewed.

PMID- 16287682
TI  - Emerging infectious diseases: the Bunyaviridae.
AB  - The Bunyaviridae are a large group of viruses that infect a diversity of
      arthropod vectors and animal hosts. They have a worldwide distribution and can be
      the cause of human illness ranging from mild asymptomatic infection to
      hemorrhagic fever and fatal encephalitis. The growth of the human population, the
      expansion of agricultural and economic development, climatic changes, and the
      speed and frequency of global transportation all favor the emergence of
      bunyaviruses and other arthropod borne viruses. International monitoring of the
      Bunyaviridae and a greater understanding of their ecology and biology are needed
      to prepare for future outbreaks.

PMID- 16287685
TI  - The ecology of emerging neurotropic viruses.
AB  - The authors review common themes in the ecology of emerging viruses that cause
      neurological disease. Three issues emerge. First, 49% of emerging viruses are
      characterized by encephalitis or serious neurological clinical symptoms. Second,
      all of these viruses are driven to emerge by ecological, environmental, or human
      demographic changes, some of which are poorly understood. Finally, the control of
      these viruses would be enhanced by collaborative multidisciplinary research into
      these drivers of emergence. The authors highlight this review with a case study
      of Nipah virus, which emerged in Malaysia due largely to shifts in livestock
      production and alterations to reservoir host habitat. Collaboration between
      virologists, ecologists, disease modelers and wildlife biologists has been
      instrumental in retracing the factors involved in this virus's emergence.

PMID- 16287684
TI  - Emerging zoonotic encephalitis viruses: lessons from Southeast Asia and Oceania.
AB  - The last decade of the 20th Century saw the introduction of an unprecedented
      number of encephalitic viruses emerge or spread in the Southeast Asian and
      Western Pacific regions (Mackenzie et al, 2001; Solomon, 2003a). Most of these
      viruses are zoonotic, either being arthropod-borne viruses or bat-borne viruses.
      Thus Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has spread
      through the Indonesian archipelago to Papua New Guinea (PNG) and to the islands
      of the Torres Strait of northern Australia, to Pakistan, and to new areas in the
      Indian subcontinent; a strain of tick-borne encephalitis virus (TBEV) was
      described for the first time in Hokkaido, Japan; and a novel mosquito-borne
      alphavirus, Me Tri virus, was described from Vietnam. Three novel bat-borne
      viruses emerged in Australia and Malaysia; two, Hendra and Nipah viruses,
      represent the first examples of a new genus in the family Paramyxoviridae, the
      genus Henipaviruses, and the third, Australian bat lyssavirus (ABLV) is new
      lyssavirus closely related to classical rabies virus. These viruses will form the
      body of this brief review.

PMID- 16287686
TI  - Emerging diseases: measles.
AB  - High vaccination coverage rates and the administration of a second dose of
      measles vaccine have resulted in a significant decline in the incidence of
      measles and neurologic diseases due to measles in many countries. However,
      intermittent outbreaks of measles still occur even in countries with excellent
      vaccination coverage, suggesting the existence of high rates of measles virus
      introduction from endemic regions and/or waning of vaccine-induced immunity.
      Strategies to sustain high levels of global immunity to measles virus by
      increasing vaccine coverage with routine and supplementary vaccination campaigns
      must be supported.

PMID- 16287689
TI  - Scrapie pathogenesis in brain and retina: effects of prion protein expression in
      neurons and astrocytes.
AB  - Brain damage in the transmissible spongiform encephalopathies or prion diseases
      is associated with the conversion of normal host prion protein to an abnormal
      protease-resistant isoform, and expression of prion protein is required for
      susceptibility to these diseases. This article reviews the data on studies using
      transgenic mice expressing prion protein in specific individual cell types to
      study the roles of these cell types in prion disease pathogenesis. Surprisingly
      damage to neurons in brain and retina appeared to require different prion protein
      expressing cells, suggesting that different pathogenic mechanisms operate in
      these two neuronal tissues.

PMID- 16287688
TI  - West Nile virus--an old virus learning new tricks?
AB  - West Nile virus (WNV) has spread across the United States causing annual
      outbreaks since its emergence in 1999. Although severe disease develops only in
      about 1% of infections, WNV has claimed a total of 564 lives in the 5 years from
      1999 to 2003. Observation of flaccid paralysis due to WNV infection at a higher
      incidence than previously documented and the devastating mortality recorded in
      infected American bird species triggered concerns about a potentially enhanced
      virulence of this virus. Here we summarize recent observations made during the
      American outbreaks regarding host range and transmission modes of WNV, and
      discuss epidemiological aspects of the emergence of this pathogen in the new
      habitat.

PMID- 16287687
TI  - The severe acute respiratory syndrome (SARS).
AB  - The world was shocked in early 2003 when a pandemic of severe acute respiratory
      syndrome (SARS) was imminent. The outbreak of this novel disease, caused by a
      novel coronavirus (the SARS-coronavirus), hit hardest in the Asian Pacific
      region, though eventually it spread to five continents. The speed of the spread
      of the SARS epidemic was unprecedented due to the highly efficient
      intercontinental transportation. An international collaborative effort through
      the World Health Organization (WHO) has helped to identify the aetiological agent
      about 1 month after the onset of the epidemic. The power of molecular biology and
      bioinformatics has enabled the complete decoding of the viral genome within
      weeks. Over 1000 publications on the phylogeny, epidemiology, genomics,
      laboratory diagnostics, antiviral, immunization, pathogenesis, clinical disease,
      and management accumulated within just 1 year. Although the exact animal
      reservoir of virus and how it evolved into a human pathogen are still obscure,
      accurate diagnosis and epidemiological control of the disease are now possible.
      This article reviews what is currently known about the virus and the disease.

PMID- 16287692
TI  - No relationship between serum cholesterol and suicidal ideation and depression in
      African-American diabetics.
AB  - Low serum cholesterol has been associated with suicidal behavior. Depression has
      been postulated to be a mediating factor between low serum cholesterol and
      suicidal behavior. Therefore, this possibility was examined in a large group of
      459 diabetic patients that had blood drawn for serum cholesterol levels on the
      same day that they completed the Beck Depression Inventory. The results failed to
      show any significant relationship between serum cholesterol levels and either
      total Beck Depression Inventory (BDI) scores or BDI scores on the item measuring
      current suicidal ideation. The limitations of the study are discussed.

PMID- 16287691
TI  - High cholesterol, triglycerides, and body-mass index in suicide attempters.
AB  - Low cholesterol concentrations and cholesterol-lowering therapies have been
      suggested to be associated with increased suicidality. This article examined the
      association of cholesterol, triglycerides, and body-mass index (BMI) with
      suicidal ideation and suicide attempts. Findings are based on a nationally
      representative community sample of n = 4,181 subjects (18-65 years) examined with
      a standardized diagnostic interview (CIDI) for (DSM-IV) mental disorders.
      Controlling for age and gender the study revealed a moderate positive association
      between cholesterol, triglycerides, BMI, and suicide attempts in subjects with
      depressive symptoms during the past 12 months (n = 1,205). The results of this
      study are compatible with two recent epidemiological cohort studies showing a
      positive association between cholesterol and completed suicide.

PMID- 16287690
TI  - Nipah virus: an emergent paramyxovirus causing severe encephalitis in humans.
AB  - Nipah virus is a recently emergent paramyxovirus that is capable of causing
      severe disease in both humans and animals. The first outbreak of Nipah virus
      occurred in Malaysia and Singapore in 1999 and, more recently, outbreaks were
      detected in Bangladesh. In humans, Nipah virus causes febrile encephalitis with
      respiratory syndrome that has a high mortality rate. The reservoir for Nipah
      virus is believed to be fruit bats, and humans are infected by contact with
      infected bats or by contact with an intermediate animal host such as pigs. Person
      to person spread of the virus has also been described. Nipah virus retains many
      of the genetic and biologic properties found in other paramyxoviruses, though it
      also has several unique characteristics. However, the virologic characteristics
      that allow the virus to cause severe disease over a broad host range, and the
      epidemiologic, environmental and virologic features that favor transmission to
      humans are unknown. This review summarizes what is known about the virology,
      epidemiology, pathology, diagnosis and control of this novel pathogen.

PMID- 16287693
TI  - A discussion of the value of cross-cultural studies in search of the meaning(s)
      of suicidal behavior and the methodological challenges of such studies.
AB  - The main purposes of this study was to test the psychometric properties of a
      questionnaire on attitudes towards suicide in a cross-cultural setting, and to
      discuss the value of cross-cultural studies in the search of meaning(s) of
      suicidal behavior as well as the methodological challenges encountered in such
      studies. Data on attitudes towards suicide among health and social science
      students from Norway and Uganda were employed to illustrate the points made. Both
      exploratory and confirmatory factor analyses showed different factor structures
      in the two countries. Whether this result is due to different latent variables
      indicating differences in meaning(s) of suicidal behavior between the two
      countries or lack of reliability and/or validity of the instrument is discussed.

PMID- 16287694
TI  - Soldiers who kill themselves: the contribution of dispositional and situational
      factors.
AB  - The present study compared characteristics of combatant and non-combatant Israeli
      soldiers (ages 18-21), who committed suicide (N = 429) with others who did not
      commit suicide (N = 499). Measures of pre-military psychological characteristics
      and data reflecting adjustment to service were culled from army records. Findings
      indicated that, in comparison to non-suicide soldiers (NS-soldiers), soldiers who
      committed suicide (S-soldiers) had greater behavioral adjustment and motivation
      to serve. In addition, as compared to non-combatant S-soldiers, combatant S
      soldiers had fewer referrals for psychological evaluation, higher sense of duty
      and autonomy scores and fewer unit changes. Excessive motivation to excel in the
      army, and the tendency to be autonomous and independent, may account for suicide
      among combatant S-soldiers, whereas personality weaknesses may have an impact on
      suicide among non-combatants. Practical implications for the disclosure of
      suicide risk and for preventive efforts in both groups are discussed.

PMID- 16287695
TI  - National differences in predictors of suicide among young and elderly citizens:
      linking societal predictors to psychological factors.
AB  - Suicide is usually conceptualized as arising either because of social phenomena
      or individual dynamics. In this study, these approaches were combined by
      analyzing suicide rates of younger people aged 15-24 and elderly aged 65-74 from
      54 nations using societal variables in conjunction with psychological measures of
      citizen characteristics as mediators. A mediated analysis showed that
      psychological citizen factors, like home satisfaction and happiness, mediated the
      impact of societal variables, like the sex ratio, in predicting suicide rates. We
      found different psychological and societal predictors for young and elderly
      suicides, with elderly suicide rates being much more predictable. An age
      responsive Durkheimian framework focusing on the dynamics of social integration
      at different ages was used to interpret these results.

PMID- 16287696
TI  - A prospective study of noncompliance with medication, suicidal ideation, and
      suicidal behavior in recently discharged psychiatric inpatients.
AB  - Discharged psychiatric inpatients are at a greater risk of suicide in the three
      months following discharge. However, risk factors for this group are not clear.
      In this study 69 psychiatric inpatients were recruited and suicidal ideation,
      insight and compliance scores were measured at discharge and 12 weeks post
      discharge. There were clinically significant rates of suicidal ideation (52%) and
      deliberate self harm (28%) in the post-discharge period. Over half of patients
      (52%) became noncompliant with medication. Subjects with lower insight scores at
      discharge were significantly more likely to become noncompliant. Suicidal
      ideation scores increased irrespective of compliance from discharge to follow-up
      and this increase was significantly greater in noncompliant subjects. We conclude
      that noncompliance with medication is associated with suicidal ideation.

PMID- 16287697
TI  - The transformation of suicide fluctuation in Slovenia.
AB  - The fluctuating rate of suicide associated with seasonal changes is present
      throughout the world. An evaluation of Slovene suicide and meteorological data
      confirm a significant fluctuation of suicide incidence between the same months of
      consecutive years from 1985 to 1993. This phenomenon has been observed in all
      months of the year, but especially during the spring months. The research results
      confirm a significant correlation between suicide incidence and temperature and
      suicide incidence and the number of sunny hours for 1985 to 1993. The lack of
      significant correlation between the meteorological data and suicide incidence
      starting in 1994 may be interpreted as a decreasing meteorological influence on
      suicide incidence due to increase in antidepressant use.

PMID- 16287699
TI  - Altruistic suicide: update.

PMID- 16287698
TI  - Suicide and islam.
AB  - Much of the research on suicidal behavior in Muslim countries has been simple
      descriptive studies of samples of completed and attempted suicides. Despite this,
      and despite the possible under-reporting of suicidal behavior in countries where
      such behavior is illegal, suicide rates do appear to be lower in Muslims than in
      those of other religions, even in countries which have populations belonging to
      several religious groups. Rates of attempted suicide, on the other hand, do not
      appear to be lower in Muslims as compared to non-Muslims. Research into this
      topic has been quite poor, failing to take into account the ethnic background and
      the Islamic sect to which the suicidal subjects belonged. Reasons for the low
      rate of completed suicide in Muslims are reviewed, including differences in
      values and socio-economic status.

PMID- 16287700
TI  - Parental report of the early development of children with regressive autism: the
      delays-plus-regression phenotype.
AB  - Most children with autism demonstrate developmental abnormalities in their first
      year, whereas others display regression after mostly normal development. Few
      studies have examined the early development of the latter group. This study
      developed a retrospective measure, the Early Development Questionnaire (EDQ), to
      collect specific, parent-reported information about development in the first 18
      months. Based on their EDQ scores, 60 children with autism between the ages of 3
      and 9 were divided into three groups: an early onset group (n = 29), a definite
      regression group (n = 23), and a heterogeneous mixed group (n = 8). Significant
      differences in early social development were found between the early onset and
      regression groups. However, over 50 percent of the children who experienced a
      regression demonstrated some early social deficits during the first year of life,
      long before regression and the apparent onset of autism. This group, tentatively
      labeled 'delays-plus-regression', deserves further study.

PMID- 16287702
TI  - Parents' experiences of introducing everyday object use to their children with
      autism.
AB  - A semi-structured interview study, investigating the acquisition of everyday
      object use in children with autism and developmentally matched controls, is
      presented. Parents were asked to describe how their child currently used various
      everyday objects during mealtime and washing routines, the process by which this
      came about, and any problems encountered in attempting to introduce appropriate
      object use. Following transcription, the interviews were treated using a method
      combining phenomenological and content analysis. The statements generated were
      condensed, using progressive categorization, into three tables of summary
      statements. These represented the different sources of influence on the
      children's object use and the problems parents experienced in attempting to guide
      their child's actions. Relative to comparison groups, parents of children with
      autism reported that they experienced more problems and used more intensive
      teaching methods, and that their children were less actively involved. The
      findings are discussed in relation to the influence of other people in shaping
      object use and implications for intervention programmes.

PMID- 16287701
TI  - Neonatal factors in infants with Autistic Disorder and typically developing
      infants.
AB  - The prenatal and neonatal factors of 225 children diagnosed with Autistic
      Disorder were compared with those of 1580 typically developing children. Each of
      the neonatal factors was compared between the Autistic Disorder and control
      groups, and between males and females. The results showed that males in the
      'Autistic Disorder' group had a significantly longer gestational age and a
      heavier birth weight than the male controls. No significant differences in these
      factors were observed between females in the two groups. Both male and female
      children with Autistic Disorder showed a significantly higher incidence of
      neonatal complications than their respective controls. In the Autistic Disorder
      group, males had a heavier mean birth weight, and there were more post-term
      infants among females.

PMID- 16287703
TI  - An experimental investigation of the phenomenology of delusional beliefs in
      people with Asperger syndrome.
AB  - There is evidence that Asperger syndrome is associated with delusional beliefs.
      Cognitive theories of delusions in psychosis literature propose a central role
      for impaired theory of mind ability in the development of delusions. The present
      study investigates the phenomenology of delusional ideation in Asperger syndrome.
      Fortysix individuals with Asperger syndrome participated and were found to have
      relatively high levels of delusional ideation, primarily grandiose or
      persecutory. Factors associated with delusional belief were anxiety, social
      anxiety and self-consciousness, but not theory of mind ability or
      autobiographical memory. The findings indicate that delusional belief is a
      prominent feature in Asperger syndrome, but do not support a mentalization based
      account. A preliminary cognitive model of delusions in Asperger syndrome is
      proposed and the theoretical and clinical implications of the findings are
      discussed.

PMID- 16287704
TI  - An 8 year follow-up of a specialist supported employment service for high-ability
      adults with autism or Asperger syndrome.
AB  - Few supported employment programmes have been specifically designed for people
      with autism, especially those who are more able. This study examines the outcome
      of a supported employment service (NAS Prospects) for adults with autism or
      Asperger syndrome (IQ 60+) over an 8 year period. Approximately 68 percent of
      clients found employment. Of the 192 jobs, the majority were permanent contracts
      and most involved administrative, technical or computing work. Assessment of
      current clients indicates that IQ, language skills and educational attainments
      are high. However, work has also been found for those of lower abilities.
      Individuals supported by Prospects show a rise in salaries, contribute more tax
      and claim fewer benefits. Satisfaction with the scheme is high among clients,
      employers and support workers. Although the programme continues to incur a
      financial deficit, this has decreased. Moreover, there are many non-financial
      benefits, which are difficult to quantify. The importance of specialist
      employment support of this kind is discussed.

PMID- 16287705
TI  - The sex of the sibs of probands with autism.

PMID- 16287708
TI  - Explaining social inequalities in health by sleep: the Japanese civil servants
      study.
AB  - BACKGROUND: Individuals of low socioeconomic status (SES) are likely to have poor
      sleep and poor health. This study aims to evaluate whether and how much of the
      socioeconomic differences in health are explained by sleep. METHODS: The subjects
      were 3684 (2471 males and 1213 females) employees aged 20-65 working in local
      government in Japan. A questionnaire survey was conducted in January 2003.
      Analysis of covariance (ANCOVA) was performed to examine the association of
      employment-grade with sleep, measured by the Pittsburgh Sleep Quality Index
      (PSQI), and with health, measured by the Physical and Mental Component Summary
      Scales (PCS and MCS) of the Short Form-36 (SF-36). RESULTS: In men, higher grade
      employees had better sleep and better health. The age-adjusted difference between
      the highest and the lowest grade employees was 1.9 points (95% confidence
      interval = 1.0-3.0) in the PCS and 3.4 points (1.8-4.9) in the MCS. The grade
      difference in health reduced to 1.5 points (0.5-2.5) in the PCS (21.1% reduction)
      and 2.0 points (0.6-3.4) in the MCS (41.2% reduction), when the PSQI global score
      was adjusted for. The grade differences in sleep quality contributed more to the
      health inequalities than sleep quantity. Among women, no significant grade
      differences were observed in the PSQI global score. The grade differences in the
      PCS and MCS were weaker and less consistent than those of men, and the
      differences hardly changed when the PSQI global score was adjusted for.
      CONCLUSION: Sleep quality may mediate the relationship between SES and physical
      and, in particular, mental health in men.

PMID- 16287709
TI  - Coordinated oncogenic transformation and inhibition of host immune responses by
      the PAX3-FKHR fusion oncoprotein.
AB  - Tumors have evolved elaborate mechanisms for evading immune detection, such as
      production of immunoinhibitory cytokines and down-regulation of major
      histocompatibility complex (MHC) expression. We have studied PAX3-FKHR as an
      example of an oncogenic fusion protein associated with an aggressive metastatic
      cancer. We show that PAX3-FKHR alters expression of genes that are normally
      regulated by Janus kinase/signal transducer and activator of transcription (STAT)
      signaling pathways. This occurs as a result of a specific interaction between
      PAX3-FKHR and the STAT3 transcription factor, which results in a dramatic
      reduction in tumor MHC expression, and an alteration in local cytokine
      concentrations to inhibit surrounding inflammatory cells and immune detection.
      Collectively, these data show that an oncogenic transcription factor can promote
      tumor growth and tissue invasion while inhibiting local inflammatory and immune
      responses. This is the first time that an immunomodulatory role has been
      described for an oncogenic fusion protein.

PMID- 16287710
TI  - Sequential development of interleukin 2-dependent effector and regulatory T cells
      in response to endogenous systemic antigen.
AB  - Transfer of naive antigen-specific CD4(+) T cells into lymphopenic mice that
      express an endogenous antigen as a systemic, secreted protein results in severe
      autoimmunity resembling graft-versus-host disease. T cells that respond to this
      endogenous antigen develop into effector cells that cause the disease. Recovery
      from this disease is associated with the subsequent generation of FoxP3(+)CD25(+)
      regulatory cells in the periphery. Both pathogenic effector cells and protective
      regulatory cells develop from the same antigen-specific T cell population after
      activation, and their generation may occur in parallel or sequentially.
      Interleukin (IL)-2 plays a dual role in this systemic T cell reaction. In the
      absence of IL-2, the acute disease is mild because of reduced T cell effector
      function, but a chronic and progressive disease develops late and is associated
      with a failure to generate FoxP3(+) regulatory T (T reg) cells in the periphery.
      Thus, a peripheral T cell reaction to a systemic antigen goes through a phase of
      effector cell-mediated pathology followed by T reg cell-mediated recovery, and
      both require the growth factor IL-2.

PMID- 16287712
TI  - Gadd45 beta and Gadd45 gamma are critical for regulating autoimmunity.
AB  - The number of effector T cells is controlled by proliferation and programmed cell
      death. Loss of these controls on self-destructive effector T cells may
      precipitate autoimmunity. Here, we show that two members of the growth arrest and
      DNA damage-inducible (Gadd45) family, beta and gamma, are critical in the
      development of pathogenic effector T cells. CD4(+) T cells lacking Gadd45beta can
      rapidly expand and invade the central nervous system in response to myelin
      immunization, provoking an exacerbated and prolonged autoimmune encephalomyelitis
      in mice. Importantly, mice with compound deficiency in Gadd45beta and Gadd45gamma
      spontaneously developed signs of autoimmune lymphoproliferative syndrome and
      systemic lupus erythematosus. Our findings therefore identify the
      Gadd45beta/Gadd45gamma-mediated control of effector autoimmune lymphocytes as an
      attractive novel target for autoimmune disease therapy.

PMID- 16287711
TI  - Avidity for antigen shapes clonal dominance in CD8+ T cell populations specific
      for persistent DNA viruses.
AB  - The forces that govern clonal selection during the genesis and maintenance of
      specific T cell responses are complex, but amenable to decryption by
      interrogation of constituent clonotypes within the antigen-experienced T cell
      pools. Here, we used point-mutated peptide-major histocompatibility complex class
      I (pMHCI) antigens, unbiased TCRB gene usage analysis, and polychromatic flow
      cytometry to probe directly ex vivo the clonal architecture of antigen-specific
      CD8(+) T cell populations under conditions of persistent exposure to structurally
      stable virus-derived epitopes. During chronic infection with cytomegalovirus and
      Epstein-Barr virus, CD8(+) T cell responses to immunodominant viral antigens were
      oligoclonal, highly skewed, and exhibited diverse clonotypic configurations; TCRB
      CDR3 sequence analysis indicated positive selection at the protein level.
      Dominant clonotypes demonstrated high intrinsic antigen avidity, defined strictly
      as a physical parameter, and were preferentially driven toward terminal
      differentiation in phenotypically heterogeneous populations. In contrast,
      subdominant clonotypes were characterized by lower intrinsic avidities and
      proportionately greater dependency on the pMHCI-CD8 interaction for antigen
      uptake and functional sensitivity. These findings provide evidence that
      interclonal competition for antigen operates in human T cell populations, while
      preferential CD8 coreceptor compensation mitigates this process to maintain
      clonotypic diversity. Vaccine strategies that reconstruct these biological
      processes could generate T cell populations that mediate optimal delivery of
      antiviral effector function.

PMID- 16287713
TI  - The many roads to cross-presentation.
AB  - Cross-presentation of extracellular antigens by MHC class I molecules is required
      for priming cytotoxic T lymphocytes (CTLs) at locations remote from the site of
      infection. Various mechanisms have been proposed to explain cross-presentation.
      One such mechanism involves the fusion of the endoplasmic reticulum (ER) with the
      endosomal-phagosomal system, in which the machinery required for peptide loading
      of MHC class I molecules is introduced directly into the phagosome. Here, we
      discuss the evidence for and against the ER-phagosome concept as well as other
      possible mechanisms of cross-presentation.

PMID- 16287714
TI  - A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals
      an essential role for SWI/SNF-related complexes in beta-globin expression and
      erythroid development.
AB  - The Brg1 catalytic subunit of SWI/SNF-related complexes has been implicated in
      many developmental and physiological processes, but null homozygotes die as
      blastocysts prior to implantation. To circumvent this early embryonic lethality,
      we performed an ENU mutagenesis screen and generated a Brg1 hypomorph mutation in
      the ATPase domain. The mutant Brg1 protein is stable, assembles into SWI/SNF
      related complexes, and exhibits normal ATPase activity but is unable to establish
      DNase I hypersensitivity sites characteristic of open chromatin. Mutant embryos
      develop normally until midgestation but then exhibit a distinct block in the
      development of the erythroid lineage, leading to anemia and death. The mutant
      Brg1 protein is recruited to the beta-globin locus, but chromatin remodeling and
      transcription are perturbed. Histone acetylation and DNA methylation are also
      affected. To our knowledge, Brg1 is the first chromatin-modifying factor shown to
      be required for beta-globin regulation and erythropoiesis in vivo. Not only does
      this mutation establish a role for Brg1 during organogenesis, it also
      demonstrates that ATPase activity can be uncoupled from chromatin remodeling.

PMID- 16287715
TI  - Molecular mechanism of light responses in Neurospora: from light-induced
      transcription to photoadaptation.
AB  - Blue light regulates many molecular and physiological activities in a large
      number of organisms. In Neurospora crassa, a eukaryotic model system for studying
      blue-light responses, the transcription factor and blue-light photoreceptor WHITE
      COLLAR-1 (WC-1) and its partner WC-2 are central to blue-light sensing.
      Neurospora's light responses are transient, that is, following an initial acute
      phase of induction, light-regulated processes are down-regulated under continuous
      illumination, a phenomenon called photoadaptation. The molecular mechanism(s) of
      photoadaptation are not well understood. Here we show that a common mechanism
      controls the light-induced transcription of immediate early genes (such as frq,
      al-3, and vvd) in Neurospora, in which light induces the binding of identical
      large WC-1/WC-2 complexes (L-WCC) to the light response elements (LREs) in their
      promoters. Using recombinant proteins, we show that the WC complexes are
      functional without the requirement of additional factors. In vivo, WCC has a long
      period photocycle, indicating that it cannot be efficiently used for repeated
      light activation. Contrary to previous expectations, we demonstrate that the
      light-induced hyperphosphorylation of WC proteins inhibits bindings of the L-WCC
      to the LREs. We show that, in vivo, due to its rapid hyperphosphorylation, L-WCC
      can only bind transiently to LREs, indicating that WCC hyperphosphorylation is a
      critical process for photoadaptation. Finally, phosphorylation was also shown to
      inhibit the LRE-binding activity of D-WCC (dark WC complex), suggesting that it
      plays an important role in the circadian negative feedback loop.

PMID- 16287716
TI  - Slicer function of Drosophila Argonautes and its involvement in RISC formation.
AB  - Argonaute proteins play important yet distinct roles in RNA silencing. Human
      Argonaute2 (hAgo2) was shown to be responsible for target RNA cleavage ("Slicer")
      activity in RNA interference (RNAi), whereas other Argonaute subfamily members do
      not exhibit the Slicer activity in humans. In Drosophila, AGO2 was shown to
      possess the Slicer activity. Here we show that AGO1, another member of the
      Drosophila Argonaute subfamily, immunopurified from Schneider2 (S2) cells
      associates with microRNA (miRNA) and cleaves target RNA completely complementary
      to the miRNA. Slicer activity is reconstituted with recombinant full-length AGO1.
      Thus, in Drosophila, unlike in humans, both AGO1 and AGO2 have Slicer functions.
      Further, reconstitution of Slicer activity with recombinant PIWI domains of AGO1
      and AGO2 demonstrates that other regions in the Argonautes are not strictly
      necessary for small interfering RNA (siRNA)-binding and cleavage activities. It
      has been shown that in circumstances with AGO2-lacking, the siRNA duplex is not
      unwound and consequently an RNA-induced silencing complex (RISC) is not formed.
      We show that upon addition of an siRNA duplex in S2 lysate, the passenger strand
      is cleaved in an AGO2-dependent manner, and nuclease-resistant modification of
      the passenger strand impairs RISC formation. These findings give rise to a new
      model in which AGO2 is directly involved in RISC formation as "Slicer" of the
      passenger strand of the siRNA duplex.

PMID- 16287717
TI  - FGF-dependent Notch signaling maintains the spinal cord stem zone.
AB  - Generation of the spinal cord relies on proliferation of undifferentiated cells
      located in a caudal stem zone. Although fibroblast growth factor (FGF) signaling
      is required to maintain this cell group, we do not know how it controls cell
      behavior in this context. Here we characterize an overlooked expression domain of
      the Notch ligand, Delta1, in the stem zone and demonstrate that this constitutes
      a proliferative cell group in which Notch signaling is active. We show that FGF
      signaling is required for expression of the proneural gene cash4 in the stem
      zone, which in turn induces Delta1. We further demonstrate that Notch signaling
      is required for cell proliferation within the stem zone; however, it does not
      regulate cell movement out of this region, nor is loss of Notch signaling
      sufficient to drive neuronal differentiation within this tissue. These data
      identify a novel role for the Notch pathway during vertebrate neurogenesis in
      which signaling between high Delta1-expressing cells maintains the neural
      precursor pool that generates the spinal cord. Our findings also suggest a
      mechanism for the establishment of the cell selection process, lateral
      inhibition: Mutual inhibition between Delta/Notch-expressing stem zone cells
      switches to single Delta1-presenting neurons as FGF activity declines in the
      newly formed neuroepithelium.

PMID- 16287719
TI  - Cholinergic septo-hippocampal innervation is required for trace eyeblink
      classical conditioning.
AB  - We studied the effects of a selective lesion in rats, with 192-IgG-saporin, of
      the cholinergic neurons located in the medial septum/diagonal band (MSDB) complex
      on the acquisition of classical and instrumental conditioning paradigms. The MSDB
      lesion induced a marked deficit in the acquisition, but not in the retrieval, of
      eyeblink classical conditioning using a trace paradigm. Such a deficit was task
      selective, as lesioned rats were able to acquire a fixed-interval operant
      conditioning as controls, and was not due to nonspecific motor alterations,
      because spontaneous locomotion and blink reflexes were not disturbed by the MSDB
      lesion. The deficit in the acquisition of a trace eyeblink classical conditioning
      was reverted by the systemic administration of carbachol, a nonselective
      cholinergic muscarinic agonist, but not by lobeline, a nicotinic agonist. These
      results suggest a key role of muscarinic denervation on the acquisition of new
      motor abilities using trace classical conditioning procedures. It might also be
      suggested that muscarinic agents would be useful for the amelioration of some
      associative learning deficits observed at early stages in patients with
      Alzheimer's disease.

PMID- 16287718
TI  - Involvement of IP3 receptors in LTP and LTD induction in guinea pig hippocampal
      CA1 neurons.
AB  - The role of inositol 1, 4, 5-trisphosphate receptors (IP3Rs) in long-term
      potentiation (LTP) and long-term depression (LTD) was studied in CA1 neurons in
      guinea pig hippocampal slices. In standard solution, short tetanic stimulation
      consisting of 15 pulses at 100 Hz induced LTP, while three short trains of low
      frequency stimulation (LFS; 200 pulses at 1 Hz) at 18-min intervals or one long
      train of LFS (1000 pulses at 1 Hz) induced stable LTD in both the slope of the
      field EPSP (S-EPSP) and the amplitude of the population spike (A-PS). Bath
      application of 2-aminoethoxydiphenyl borate (2-APB), an IP3R antagonist, or of
      alpha-methyl-4-carboxyphenylglycine (MCPG), a wide-spectrum metabotropic
      glutamate receptor antagonist, during weak tetanic stimulation significantly
      increased the magnitude of the LTP in both the S-EPSP and A-PS. Three short
      trains of LFS or one long train of LFS delivered in the presence of 2-APB or MCPG
      did not induce LTD, but elicited LTP. Based on these results, we conclude that,
      in hippocampal CA1 neurons, IP3Rs play an important role in synaptic plasticity
      by attenuating LTP and facilitating LTD.

PMID- 16287720
TI  - The role of cuticular pheromones in courtship conditioning of Drosophila males.
AB  - Courtship conditioning is an associative learning paradigm in Drosophila
      melanogaster, wherein male courtship behavior is modified by experience with
      unreceptive, previously mated females. While the training experience with mated
      females involves multiple sensory and behavioral interactions, we hypothesized
      that female cuticular hydrocarbons function as a specific chemosensory
      conditioned stimulus in this learning paradigm. The effects of training with
      mated females were determined in courtship tests with either wild-type virgin
      females as courtship targets, or with target flies of different genotypes that
      express distinct cuticular hydrocarbon (CH) profiles. Results of tests with
      female targets that lacked the normal CH profile, and with male targets that
      expressed typically female CH profiles, indicated that components of this CH
      profile are both necessary and sufficient cues to elicit the effects of
      conditioning. Results with additional targets indicated that the female-specific
      7,11-dienes, which induce naive males to court, are not essential components of
      the conditioned stimulus. Rather, the learned response was significantly
      correlated with the levels of 9-pentacosene (9-P), a compound found in both males
      and females of many Drosophila strains and species. Adding 9-P to target flies
      showed that it stimulates courting males to attempt to copulate, and confirmed
      its role as a component of the conditioned stimulus by demonstrating dose
      dependent increases in the expression of the learned response. Thus, 9-P can
      contribute significantly to the conditioned suppression of male courtship toward
      targets that express this pheromone.

PMID- 16287721
TI  - Insulin receptor signaling in long-term memory consolidation following spatial
      learning.
AB  - Evidence has shown that the insulin and insulin receptor (IR) play a role in
      cognitive function. However, the detailed mechanisms underlying insulin's action
      on learning and memory are not yet understood. Here we investigated changes in
      long-term memory-associated expression of the IR and downstream molecules in the
      rat hippocampus. After long-term memory consolidation following a water maze
      learning experience, gene expression of IR showed an up-regulation in the CA1,
      but a down-regulation in the CA3 region. These were correlated with a significant
      reduction in hippocampal IR protein levels. Learning-specific increases in levels
      of downstream molecules such as IRS-1 and Akt were detected in the synaptic
      membrane accompanied by decreases in Akt phosphorylation. Translocation of Shc
      protein to the synaptic membrane and activation of Erk1/2 were also observed
      after long-term memory formation. Despite the clear memory-correlated alterations
      in IR signaling pathways, insulin deficits in experimental diabetes mellitus (DM)
      rats induced by intraperitoneal injections of streptozotocin resulted in only
      minor memory impairments. This may be due to higher glucose levels in the DM
      brain, and to compensatory mechanisms from other signaling pathways such as the
      insulin-like growth factor-1 receptor (IGF-1R) system. Our results suggest that
      insulin/IR signaling plays a modulatory role in learning and memory processing,
      which may be compensated for by alternative pathways in the brain when an insulin
      deficit occurs.

PMID- 16287722
TI  - Enhancement of auditory fear conditioning after housing in a complex environment
      is attenuated by prior treatment with amphetamine.
AB  - Prior exposure to drugs of abuse has been shown to occlude the structural
      plasticity associated with living in a complex environment. Amphetamine treatment
      may also occlude some cognitive advantages normally associated with living in a
      complex environment. To test this hypothesis we examined the influence of prior
      exposure to amphetamine on fear conditioning in rats housed in either a standard
      or complex environment. Housing in a complex environment facilitated fear
      learning to an auditory conditioned stimulus (CS), but not to the training
      context, relative to animals housed singly or in a social group. Prior treatment
      with amphetamine eliminated this effect. These results indicate that living in a
      complex environment facilitates conditional freezing to an auditory CS, and that
      this effect is abolished by pretreatment with amphetamine.

PMID- 16287723
TI  - A latent cue preference based on sodium depletion in rats.
AB  - Three experiments show latent (or incidental) learning of salt-cue relationships
      using a conditioned cue-preference paradigm. Rats drank a salt solution while
      confined in one compartment and water in an adjacent, distinct compartment on
      alternate days. When given access to the two compartments with no solutions
      present, sodium-deprived rats preferred their salt-paired compartments; normal
      rats preferred their water-paired compartments. Reversing the deprivation states
      of the two groups reversed their preferences. These results show that rats can
      latently acquire associations between environmental cues and the taste of salt,
      and can use this information flexibly to guide behavior based upon internal cues
      produced by sodium deprivation.

PMID- 16287725
TI  - Atrial fibrillation ablation in the real world.
AB  - While the potential for curative treatment of atrial fibrillation has generated
      much interest in the role of catheter ablation, its widespread use has been
      limited by a number of factors.

PMID- 16287727
TI  - Images in cardiology: asymptomatic inferior vena cava anomaly in an adult: three
      dimensional multislice CT image.

PMID- 16287726
TI  - Images in cardiology: an unusual cause of syncope.

PMID- 16287724
TI  - Theta frequency stimulation induces a local form of late phase LTP in the CA1
      region of the hippocampus.
AB  - The late phase of LTP (L-LTP) is typically induced by repeated high-frequency
      stimulation. This form of LTP requires activation of transcription and
      translation and results in the cell-wide distribution of gene products that can
      be captured by other marked synapses. Here we report that theta frequency
      stimulation (5 Hz, 30 sec) applied to the Schaeffer-collateral pathway can induce
      a form of late phase of LTP that is restricted locally to the dendritic
      compartment. The late phase of theta frequency LTP is maintained even in isolated
      CA1 dendrites and is dependent on dendritic translation and actin cytoskeletal
      regulation, but is independent of transcription. This local form of L-LTP is not
      accessible to synaptic capture by other synapses, indicating that this form of
      LTP is restricted to the synaptic compartment. These results indicate that
      different patterns of synaptic stimulation can induce distinct forms of LTP that
      may have different roles in memory storage.

PMID- 16287729
TI  - Images in cardiology: mid cavity hypertrophic cardiomyopathy.

PMID- 16287728
TI  - Multidetector row computed tomography: imaging congenital coronary artery
      anomalies in adults.
AB  - The quality of the imaging of the main coronary arteries and side branches
      provided by multidetector row computed tomography (MDCT) may have importance when
      assessing congenital coronary artery anomalies. This review discusses the
      rationale for using MDCT for this indication and examines the advantages and
      disadvantages of the technique. Examples of MDCT imaging of congenital coronary
      artery anomalies are presented. These images provide persuasive evidence to
      support clinical use of MDCT cardiac imaging in the context of suspected
      congenital coronary artery anomalies as a first line investigation.

PMID- 16287730
TI  - Images in cardiology: crossing epicardial coronary arteries.

PMID- 16287731
TI  - It's a matter of time: contemporary pre-hospital management of acute ST elevation
      myocardial infarction.

PMID- 16287732
TI  - Facilitated percutaneous coronary intervention.

PMID- 16287733
TI  - Images in cardiology: siblings with supravalvar aortic stenosis.

PMID- 16287735
TI  - Images in cardiology: giant left ventricular thrombus after radiofrequency
      ablation of post-infarction ventricular tachycardia: what to do?

PMID- 16287734
TI  - Management of microvascular dysfunction and reperfusion injury.

PMID- 16287737
TI  - Images in cardiology: echinococcal cyst mimicking myocardial infarction.

PMID- 16287736
TI  - Recent advances in primary percutaneous intervention for acute myocardial
      infarction.

PMID- 16287738
TI  - Images in cardiology: coronary-cameral fistula.

PMID- 16287739
TI  - Relation of arterial stiffness to diastolic dysfunction in hypertensive heart
      disease.
AB  - OBJECTIVES: To examine the relation of arterial compliance to diastolic
      dysfunction in hypertensive patients with suspected diastolic heart failure (HF).
      PATIENTS: 70 medically treated hypertensive patients with exertional dyspnoea (40
      women, mean (SD) age 58 (8) years) and 15 normotensive controls. MAIN OUTCOME
      MEASURES: Mitral annular early diastolic velocity with tissue Doppler imaging and
      flow propagation velocity were used as linear measures of diastolic function.
      Arterial compliance was determined by the pulse pressure method. RESULTS:
      According to conventional Doppler echocardiography of transmitral and pulmonary
      venous flow, diastolic function was classified as normal in 33 patients and
      abnormal in 37 patients. Of those with diastolic dysfunction, 28 had mild
      (impaired relaxation) and nine had advanced (pseudonormal filling) dysfunction.
      Arterial compliance was highest in controls (mean (SD) 1.32 (0.58) ml/mm Hg) and
      became progressively lower in patients with hypertension and normal function
      (1.04 (0.37) ml/mm Hg), impaired relaxation (0.89 (0.42) ml/mm Hg), and
      pseudonormal filling (0.80 (0.45) ml/mm Hg, p = 0.011). In patients with
      diastolic dysfunction, arterial compliance was inversely related to age (p =
      0.02), blood pressure (p < 0.001), and estimated filling pressures (p < 0.01) and
      directly related to diastolic function (p < 0.01). After adjustment for age, sex,
      body size, blood pressure, and ventricular hypertrophy, arterial compliance was
      independently predictive of diastolic dysfunction. CONCLUSIONS: In hypertensive
      patients with exertional dyspnoea, progressively abnormal diastolic function is
      associated with reduced arterial compliance. Arterial compliance is an
      independent predictor of diastolic dysfunction in patients with hypertensive
      heart disease and should be considered a potential target for intervention in
      diastolic HF.

PMID- 16287740
TI  - Predictors of poor mid-term health related quality of life after primary isolated
      coronary artery bypass grafting surgery.
AB  - OBJECTIVE: To assess the determinants of poor mid-term health related quality of
      life (HRQoL) at one year after primary isolated coronary artery bypass grafting
      (CABG). METHODS: 463 patients who underwent primary isolated CABG for multivessel
      disease and came for their annual follow up at the outpatient clinic during one
      year at Harefield Hospital, Middlesex, were approached to participate in the
      present study. Prospective clinical data were collected as part of the clinical
      care of the patients and were retrospectively analysed when the patients
      consented to participate in the study at their outpatient visit. After their
      consent they were given three HRQoL assessment questionnaires. Scores, together
      with clinical data, were analysed by both univariate and multivariate analyses
      with regard to poor HRQoL outcome. RESULTS: 437 (94.4%) patients consented to
      participate in the study and filled in the HRQoL questionnaires. Ten variables
      were identified in the univariate analysis as potential predictors of poor scores
      of the physical element of HRQoL; however, only three variables-gastrointestinal
      problems, congestive heart failure, and type D personality trait-predicted poor
      physical scores independently. Eleven variables were identified in the univariate
      analysis as potential predictors of poor scores of the mental element of HRQoL;
      however, only three variables-peripheral vascular disease, infective
      complications, and type D personality trait-predicted poor physical scores
      independently. CONCLUSION: Preoperative gastrointestinal problems, preoperative
      congestive heart failure, and type D personality trait were independent
      predictors of the poor physical component of HRQoL. Peripheral vascular disease,
      infective complications, and type D personality trait were independent predictors
      of the poor mental component of HRQoL. Interestingly, patients with type D
      personality were more than twice as likely to have poor physical HRQoL and more
      than five times as likely to have poor mental HRQoL.

PMID- 16287741
TI  - Images in cardiology: neovascularisation of giant left atrial myxoma visualised
      on angiography.

PMID- 16287742
TI  - Images in cardiology: Osler-Weber-Rendu syndrome.

PMID- 16287743
TI  - Images in cardiology: scimitar syndrome.

PMID- 16287744
TI  - Fetal dextrocardia: diagnosis and outcome in two tertiary centres.
AB  - OBJECTIVE: To evaluate the incidence of fetal dextrocardia, associated cardiac
      and extracardiac malformations, and outcome. DESIGN: Retrospective
      echocardiographic study. SETTING: Two tertiary centres for fetal cardiology.
      PATIENTS: 81 consecutive fetuses with a fetal dextrocardia presenting at Guy's
      Hospital, London, between 1983 and 2003 and at Hopital Robert Debre, Paris,
      between 1988 and 2003. Fetal dextrocardia was defined as a condition in which the
      major axis of the heart points to the right. RESULTS: The incidence was 0.22%.
      There were 38 fetuses (47%) with situs solitus (SS), 24 (30%) with situs ambiguus
      (SA), and 19 (23%) with situs inversus (SI). Structural cardiac malformations
      were found in 25 cases (66%) of SS, 23 cases (96%) of SA, and 12 cases (63%) of
      SI. Extracardiac malformations were identified in 12 cases (31%) of SS, in five
      cases (21%) of SA, and in two cases (10%) of SI. Of the 81 cases of fetal
      dextrocardia, there were 27 interrupted pregnancies (15 of 24 SA, 10 of 38 SS,
      and 2 of 19 SI), six intrauterine deaths (3 of 38 SS, 2 of 24 SA, and 1 of 19
      SI), and five neonatal deaths (3 of 24 SA, 1 of 19 SI, and 1 of 38 SS). There
      were 43 survivors (24 of 38 SS, 15 of 19 SI, and 4 of 24 SA). CONCLUSION: The
      majority of fetuses with dextrocardia referred for fetal echocardiography have
      associated congenital heart disease. There is a broad spectrum of cardiac
      malformation and the incidence varies according to the atrial situs. Fetal
      echocardiography enables detection of complex congenital heart disease so that
      parents can be appropriately counselled.

PMID- 16287745
TI  - Recent respiratory infection and the risk of myocardial infarction.

PMID- 16287746
TI  - Relative importance of the components of stent geometry to stretch induced in
      stent neointima formation.

PMID- 16287747
TI  - Images in cardiology: the invisible stent: imaging of an absorbable metal stent
      with multislice spiral computed tomography.

PMID- 16287748
TI  - Serum adiponectin in coronary heart disease: ethnic differences and relation to
      coronary artery disease severity.

PMID- 16287749
TI  - Serum asymmetric dimethylarginine as a marker of coronary microcirculation in
      patients with non-insulin dependent diabetes mellitus: correlation with coronary
      flow reserve.

PMID- 16287750
TI  - Hostility is an independent predictor of recurrent coronary heart disease events
      in men but not women: results from a population based study.

PMID- 16287751
TI  - Radiofrequency ablation of atrial fibrillation: effectiveness and safety in 102
      consecutive patients.

PMID- 16287752
TI  - Images in cardiology: giant coronary aneurysm in the septal branch.

PMID- 16287753
TI  - Confirmation of a role for the 389R>G beta-1 adrenoceptor polymorphism on
      exercise capacity in heart failure.

PMID- 16287754
TI  - Images in cardiology: kidney cancer with cardiac extension.

PMID- 16287755
TI  - Radiation in the cardiac catheter laboratory.

PMID- 16287756
TI  - Diabetes and cardiovascular disease: the road to cardioprotection.

PMID- 16287757
TI  - The normal ECG in childhood and adolescence.

PMID- 16287758
TI  - Images in cardiology: cleft mitral valve assessed by transthoracic real time
      three dimensional echocardiography.

PMID- 16287759
TI  - How much and what type of physical activity is enough? What physicians should
      tell their patients.

PMID- 16287760
TI  - The tension between E-health innovation and E-valuation.

PMID- 16287761
TI  - Implications of pharmacogenomics for drug development and clinical practice.
AB  - Pharmacogenomics is likely to be among the first clinical applications of the
      Human Genome Project and is certain to have an enormous impact on the clinical
      practice of medicine. Herein, we discuss the potential implications of
      pharmacogenomics on the drug development process, including drug safety,
      productivity, market segmentation, market expansion, differentiation, and
      personalized health care. We also review 3 challenges facing the translation of
      pharmacogenomics into clinical practice: dependence on information technology,
      limited health care financing, and the scientific uncertainty surrounding
      validation of specific applications of the technology. To our knowledge, there is
      currently no formal agenda to promote and cultivate innovation, to develop
      progressive information technology, or to obtain the financing that would be
      required to advance the use of pharmacogenomic technologies in patient care.
      Although the potential of these technologies is driving change in the development
      of clinical sciences, it remains to be seen which health care systems level needs
      will be addressed.

PMID- 16287763
TI  - Atherosclerotic plaque imaging: contemporary role in preventive cardiology.
AB  - Coronary artery disease imaging has traditionally been based on luminal
      angiography, but it has become evident that this tool, although extremely useful
      in diagnosing obstructive disease, is insufficient to define the presence and
      extent of atherosclerotic disease in the vessel wall. Progression of coronary
      artery disease was also initially evaluated using quantitative coronary
      angiography, and evidence soon accumulated that minor regression or
      nonprogression of luminal disease was associated with a favorable cardiovascular
      outcome. In recent years, however, several other techniques have been developed
      to image atherosclerosis and are emerging as useful tools in preventive
      cardiovascular medicine. These techniques provide new methods to assess the
      burden of atherosclerosis, gauge the risk of cardiovascular events, and offer a
      means to test the efficacy of therapeutic approaches to atherosclerosis.
      Furthermore, noninvasive coronary angiography can be performed with some of the
      new imaging modalities, potentially reducing the number of unnecessary invasive
      tests. This review focuses on techniques such as cardiac computed tomography,
      carotid artery intima-media thickness, cardiovascular magnetic resonance imaging,
      and intravascular ultrasonography as emerging tools in cardiovascular disease
      prevention.

PMID- 16287762
TI  - The risk of lymphoma development in autoimmune diseases: a meta-analysis.
AB  - BACKGROUND: The risk of development of non-Hodgkin lymphoma (NHL) in autoimmune
      patients has been investigated in several cohort studies. These studies revealed
      inconclusive results. To shed some light on this controversy, we conducted a meta
      analysis of all available cohort studies linking systemic lupus erythematosus
      (SLE), rheumatoid arthritis (RA), and primary Sjogren syndrome (pSS) to the risk
      of NHL development. METHODS: We searched the PubMed database (1974 to April 2005)
      for English-language cohort studies using the key words systemic lupus
      erythematosus, SLE, rheumatoid arthritis, RA, Sjogren syndrome, or SS; non
      Hodgkin lymphoma; and relative risk, RR, standardized incidence rate, or SIR. All
      cohort studies that used established diagnostic criteria for SLE, RA, and pSS;
      had histologic confirmation of NHL; and provided standardized incidence rates
      (SIRs) were included in the meta-analysis. RESULTS: The 20 studies chosen for the
      analysis included 6 for SLE, 9 for RA, and 5 for pSS. Overall, the meta-analysis
      suggested extreme heterogeneity among the studies (P < .01; I2 > 70%), high risk
      of NHL development for pSS (random effects SIR, 18.8; 95% confidence interval
      [CI], 9.5-37.3); moderate risk for SLE (random effects SIR, 7.4; 95% CI, 3.3
      17.0); and lower risk for RA (random effects SIR, 3.9; 95% CI, 2.5-5.9). In RA,
      the random effects SIRs of NHL with conventional antirheumatic treatment,
      cytotoxic treatment, and treatment with a biological agent were 2.5 (95% CI, 0.7
      9.0), 5.1 (95% CI, 0.9-28.6), and 11.5 (95% CI, 3.7-26.9), respectively.
      CONCLUSIONS: Rheumatic disease may present a potential risk factor for
      development of NHL. In this regard, we focused on the underlying pathophysiologic
      mechanisms related to lymphomagenesis in pSS, SLE, and RA, to justify the varying
      potential for and background of NHL development.

PMID- 16287764
TI  - Effects of physical activity on life expectancy with cardiovascular disease.
AB  - BACKGROUND: Physical inactivity is a modifiable risk factor for cardiovascular
      disease. However, little is known about the effects of physical activity on life
      expectancy with and without cardiovascular disease. Our objective was to
      calculate the consequences of different physical activity levels after age 50
      years on total life expectancy and life expectancy with and without
      cardiovascular disease. METHODS: We constructed multistate life tables using data
      from the Framingham Heart Study to calculate the effects of 3 levels of physical
      activity (low, moderate, and high) among populations older than 50 years. For the
      life table calculations, we used hazard ratios for 3 transitions (healthy to
      death, healthy to disease, and disease to death) by levels of physical activity
      and adjusted for age, sex, smoking, any comorbidity (cancer, left ventricular
      hypertrophy, arthritis, diabetes, ankle edema, or pulmonary disease), and
      examination at start of follow-up period. RESULTS: Moderate and high physical
      activity levels led to 1.3 and 3.7 years more in total life expectancy and 1.1
      and 3.2 more years lived without cardiovascular disease, respectively, for men
      aged 50 years or older compared with those who maintained a low physical activity
      level. For women the differences were 1.5 and 3.5 years in total life expectancy
      and 1.3 and 3.3 more years lived free of cardiovascular disease, respectively.
      CONCLUSIONS: Avoiding a sedentary lifestyle during adulthood not only prevents
      cardiovascular disease independently of other risk factors but also substantially
      expands the total life expectancy and the cardiovascular disease-free life
      expectancy for men and women. This effect is already seen at moderate levels of
      physical activity, and the gains in cardiovascular disease-free life expectancy
      are twice as large at higher activity levels.

PMID- 16287765
TI  - Prescribing exercise at varied levels of intensity and frequency: a randomized
      trial.
AB  - BACKGROUND: Regular physical activity produces beneficial effects on health, but
      the exercise prescription needed to improve cardiovascular disease risk factors
      in free-living sedentary individuals remains unclear. METHODS: Sedentary adults
      (N = 492, 64.0% women) were randomized to 1 of 4 exercise-counseling conditions
      or to a physician advice comparison group. The duration (30 minutes) and type
      (walking) of exercise were held constant, while exercise intensity and frequency
      were manipulated to form 4 exercise prescriptions: moderate intensity-low
      frequency, moderate intensity-high frequency (HiF), hard intensity (HardI)-low
      frequency, and HardI-HiF. Comparison group participants received physician advice
      and written materials regarding recommended levels of exercise for health.
      Outcomes included 6- and 24-month changes in cardiorespiratory fitness (maximum
      oxygen consumption), high-density lipoprotein cholesterol (HDL-C) level, and the
      total cholesterol-HDL-C ratio. RESULTS: At 6 months, the HardI-HiF, HardI-low
      frequency, and moderate-intensity-HiF conditions demonstrated significant
      increases in maximum oxygen consumption (P < .01 for all), but only the HardI-HiF
      condition showed significant improvements in HDL-C level (P < .03), total
      cholesterol-HDL-C ratio (P < .04), and maximum oxygen consumption (P < .01)
      compared with physician advice. At 24 months, the increases in maximum oxygen
      consumption remained significantly higher than baseline in the HardI-HiF, HardI
      low-frequency, and moderate-intensity-HiF conditions and in the HardI-HiF group
      compared with physician advice (P < .01 for all), but no significant effects on
      HDL-C level (P = .57) or total cholesterol-HDL-C ratio (P = .64) were observed.
      CONCLUSIONS: Exercise counseling with a prescription for walking at either a
      HardI or a HiF produced significant long-term improvements in cardiorespiratory
      fitness. More exercise or the combination of HardI plus HiF exercise may provide
      additional benefits, including larger fitness changes and improved lipid
      profiles.

PMID- 16287766
TI  - Relationship of day-to-day reproductive hormone levels to sleep in midlife women.
AB  - BACKGROUND: We analyzed data from a single menstrual cycle from 630 women, aged
      43 to 53 years, in the Daily Hormone Study component of the Study of Women's
      Health Across the Nation to determine whether hormone levels are associated with
      trouble sleeping as women enter the menopausal transition. METHODS: Women
      recorded whether they had trouble sleeping the previous night. Morning urine
      specimens were obtained for daily determinations of levels of luteinizing
      hormone, follicle-stimulating hormone, estradiol metabolites (ie, estrone
      conjugates), and the progesterone metabolite (pregnanediol glucuronide). Women
      were categorized as premenopausal or early perimenopausal by bleeding patterns.
      RESULTS: Average adjusted odds of reporting trouble sleeping were 29% higher in
      perimenopausal than in premenopausal women. The highest percentages of women in
      both menopausal groups reported trouble sleeping in the beginning or at the end
      of their cycle. After controlling for covariates, pregnanediol glucuronide level
      was associated with increased trouble sleeping in perimenopausal women and
      follicle-stimulating hormone level was associated with increased trouble sleeping
      in premenopausal women. Mood and vasomotor symptoms were the strongest and most
      consistent cocontributors to trouble sleeping. CONCLUSION: In this community
      based sample of middle-aged women, the most trouble sleeping was observed at the
      beginning and end of the menstrual cycle.

PMID- 16287767
TI  - To tell or not to tell: primary care patients' disclosure deliberations.
AB  - BACKGROUND: Literature on patient disclosure has highlighted policy proposals,
      practitioner attitude and practices, and issues specific to already identified
      vulnerable populations (eg, human immunodeficiency virus-positive patients and
      adolescents). We investigated the topics and concerns that led less-studied
      primary care patients to deliberate disclosure to their physician and the range
      of actions taken following such deliberation. METHODS: This descriptive
      qualitative study used semistructured in-depth interviews with 85 self-selected
      female primary care patients recruited from 2 hospital-associated primary care
      practices and through advertisements in local newspapers. RESULTS: Topics that
      led subjects to deliberate over disclosure included sex, sexually transmitted
      diseases, reproductive health, drug use, mental health, and domestic
      circumstances. Concerns prompting this deliberation fell into 2 categories. The
      first, extraindividual concerns, included fear of information circulating to
      employers or insurance companies and the need to disclose for adequate treatment.
      The second, intrapersonal concerns, centered on feelings of comfort,
      embarrassment, or shame in the act of disclosing during the clinical encounter.
      While the majority of women did eventually disclose all or part of the
      information in question, a significant minority did not disclose. There were no
      significant demographic differences associated with patterns of disclosure.
      CONCLUSIONS: Primary care patients have concerns that affect and sometimes limit
      disclosure. Physicians are encouraged to explore patients' concerns about the
      uses and circulation of medical information, as well as anxiety over anticipated
      shame or embarrassment at the moment of information disclosure to physicians.
      This is especially important in primary care settings, where failure to disclose
      can mean lack of referral to needed specialized care.

PMID- 16287768
TI  - A randomized outpatient trial of a decision-support information technology tool.
AB  - BACKGROUND: Decision-support information technology is often adopted to improve
      clinical decision making, but it is rarely rigorously evaluated. Congress
      mandated the evaluation of Problem-Knowledge Couplers (PKC Corp, Burlington, Vt),
      a decision-support tool proposed for the Department of Defense's new health
      information network. METHODS: This was a patient-level randomized trial conducted
      at 2 military practices. A total of 936 patients were allocated to the
      intervention group and 966 to usual care. Couplers were applied before routine
      ambulatory clinic visits. The primary outcome was quality of care, which was
      assessed based on the total percentage of any of 24 health care quality process
      measures (opportunities to provide evidence-based care) that were fulfilled.
      Secondary outcomes included medical resources consumed within 60 days of
      enrollment and patient and provider satisfaction. RESULTS: There were 4639 health
      care opportunities (2374 in the Coupler group and 2265 in the usual-care group),
      with no difference in the proportion of opportunities fulfilled (33.9% vs 30.7%;
      P = .12). Although there was a modest improvement in performance on
      screening/preventive measures, it was offset by poorer performance on some
      measures of acute care. Coupler patients used more laboratory and pharmacy
      resources than usual-care patients (logarithmic mean difference, 71 dollars). No
      difference in patient satisfaction was observed between groups, and provider
      satisfaction was mixed. CONCLUSION: This study provides no strong evidence to
      support the utility of this decision-support tool, but it demonstrates the value
      of rigorous evaluation of decision-support information technology.

PMID- 16287769
TI  - Improving laboratory monitoring at initiation of drug therapy in ambulatory care:
      a randomized trial.
AB  - BACKGROUND: The importance of laboratory monitoring for drugs is reflected in
      product labeling and published guidelines, but monitoring recommendations are
      followed inconsistently. Opportunity exists to improve monitoring, with the
      potential to decrease therapy complications. METHODS: The objective of this
      randomized trial was to determine whether computerized alerts were effective at
      increasing the percentage of ambulatory patients with laboratory monitoring at
      initiation of drug therapy. Physicians and pharmacists teamed up to develop
      organization-specific guidelines for monitoring selected drugs. In collaboration
      with physicians, pharmacists were alerted to missing laboratory test results,
      ordered missing tests, reminded patients to obtain tests, assessed test
      completion, reviewed test results, and managed abnormal results. Eligible
      individuals included patients with therapy initiated for any of 15 drugs among
      400,000 health plan members. RESULTS: In the intervention group, 79.1% (n = 4076;
      95% confidence interval [CI], 78.0%-80.2%) of dispensings were monitored compared
      with 70.2% (n = 3522; 95% CI, 68.9%-71.5%) in the usual-care group (P < .001).
      For example, 78.6% of amiodarone (95% CI, 73.1%-83.5%) dispensing was monitored
      in the intervention group vs 51.4% (95% CI, 44.4%-58.4%) in the group receiving
      usual care (P < .001). CONCLUSIONS: This study demonstrates the effectiveness of
      a computerized tool plus collaboration among health care professionals at
      increasing the percentage of patients receiving laboratory monitoring at
      initiation of therapy. Coupling data available from information systems with the
      knowledge and skills of physicians and pharmacists can result in improved patient
      monitoring.

PMID- 16287770
TI  - Symptoms and related functioning in a traumatized community.
AB  - BACKGROUND: Traumatic events are described as precipitating factors for medically
      unexplained symptoms. The aim of this study was to examine the prevalence and
      course of symptoms reported by disaster survivors and to assess whether the
      symptoms have features similar to those of medically unexplained symptoms.
      METHODS: A 3-wave longitudinal study was performed after an explosion of a
      fireworks depot. As a result of the explosion, 23 people were killed, more than
      900 people were injured, and about 500 homes were damaged or destroyed.
      Respondents completed a set of validated questionnaires measuring their health
      problems 3 weeks (wave 1), 18 months (wave 2), and 4 years (wave 3) after the
      disaster. A comparison group was included at waves 2 and 3. RESULTS: The study
      population included 815 survivors who participated in the 3 waves. The mean
      number of symptoms was higher among survivors compared with control subjects at
      wave 2 (7.5 vs 5.8 symptoms) and at wave 3 (6.1 vs 4.9 symptoms) (P < .001 for
      both). Survivors and control subjects with more symptoms reported significantly
      lower mean scores on all scales of the Dutch version of the RAND 36-item health
      survey. Illness behavior and depression and anxiety were associated with the
      number of symptoms. For example, more than 60% of survivors with 10 or more
      symptoms reported depression and anxiety, compared with 2.4% of survivors with 0
      to 1 symptoms (P < .001). CONCLUSIONS: Up to 4 years after the disaster, symptoms
      were more prevalent among survivors than controls. Although medical disorders
      cannot be excluded, the reported symptoms showed several features similar to
      those of medically unexplained symptoms in the general population.

PMID- 16287771
TI  - Progression and regression of sleep-disordered breathing with changes in weight:
      the Sleep Heart Health Study.
AB  - BACKGROUND: The relationship of weight changes to the incidence, progression, and
      remission of sleep-disordered breathing (SDB) is not well defined. This study
      aims to determine the relationship between change in weight and progression or
      remission of SDB by polysomnography. METHODS: We performed a longitudinal cohort
      study of the cardiovascular consequences of sleep apnea in diverse US
      communities. Sleep apnea and polysomnographic indicators of SDB were assessed 5
      years apart. RESULTS: A total of 2968 men and women (mean age, 62 years)
      participated in the study. Men were more likely to have an increase in
      Respiratory Disturbance Index (RDI) with a given increase in weight than were
      women, and this was not explained by differences in starting weight, waist
      circumference, age, or ethnicity. In a linear regression analysis, both men and
      women had a greater increase in RDI with weight gain than a decrease in RDI with
      weight loss. In a categorical analysis of larger degrees of change, this sex
      difference was also evident. Associations were similar in diverse ethnic groups.
      However, SDB progressed over time, even in those with stable weight. CONCLUSION:
      Modest changes in weight were related to an increase or decrease in SDB, and this
      association was stronger in men than in women.

PMID- 16287772
TI  - Compliance with osteoporosis medications.
AB  - BACKGROUND: Long-term compliance with pharmacologic treatments for many
      asymptomatic conditions may be suboptimal, but little is known about compliance
      with medications used for osteoporosis. This study was undertaken to assess the
      level and determinants of compliance with drugs prescribed for osteoporosis.
      METHODS: This retrospective cohort study used pharmacy claims data from US
      Medicare and filled prescriptions from a state pharmaceutical benefits program.
      We included persons 65 years or older who initiated use of a medication for
      osteoporosis (alendronate sodium, calcitonin, hormone therapy, raloxifene
      hydrochloride, or risedronate) from January 1, 1996, through December 31, 2002.
      The outcome of interest was suboptimal medication compliance, defined as equal to
      or less than 66% of days with medication during a 60-day period. RESULTS: One
      year after initiating treatment for osteoporosis, 45.2% of the 40,002 patients
      were not continuing to fill prescriptions. Five years after initiation, 52.1% of
      patients were not continuing to fill prescriptions for an osteoporosis
      medication. Several characteristics independently predicted compliance: female
      sex, younger age, fewer comorbid conditions, using fewer nonosteoporosis
      medications, bone mineral density testing before and after initiating a
      medication, a fracture before and after initiating a medication, and nursing home
      residence during the 12 months before initiating a medication. However, models
      adjusted for the significant patient variables explained only 6% of the variation
      in compliance. CONCLUSIONS: Most patients who initiate a medication for
      osteoporosis do not continue to take it as prescribed. Although several patient
      characteristics significantly correlated with compliance, adjusted models
      explained little of the variation.

PMID- 16287773
TI  - A prospective study of plasma lipid levels and hypertension in women.
AB  - BACKGROUND: Although dyslipidemia and hypertension occur together more often than
      can be explained by chance, few studies have carefully explored the nature of the
      relationship between plasma lipid levels and the risk of developing hypertension.
      METHODS: We conducted a prospective study of 16 130 middle-aged and older female
      health professionals in 1992 who provided baseline blood samples and had no
      history of high cholesterol level (no treatment or diagnosis) or hypertension (no
      treatment, diagnosis, or elevated blood pressure). Plasma lipid levels were
      measured, and baseline risk factors were collected. Incident hypertension
      included a new physician diagnosis, the initiation of antihypertensive treatment,
      systolic blood pressure of 140 mm Hg or greater, or diastolic blood pressure of
      90 mm Hg or greater. RESULTS: During 10.8 years of follow-up, incident
      hypertension developed in 4593 women. In multivariate-adjusted models, the
      relative risks of development of hypertension from the lowest (referent) to the
      highest quintile of baseline total cholesterol level were 1.00, 0.96, 1.02, 1.09,
      and 1.12 (P = .002 for trend); for low-density lipoprotein cholesterol level,
      1.00, 0.97, 1.00, 1.02, and 1.11 (P = .053 for trend); for high-density
      lipoprotein cholesterol level, 1.00, 0.93, 0.87, 0.87, and 0.81 (P < .001 for
      trend); for non-high-density lipoprotein cholesterol level, 1.00, 1.06, 1.11,
      1.12, and 1.25 (P < .001 for trend); and for the ratio of total to high-density
      cholesterol, 1.00, 1.10, 1.14, 1.20, and 1.34 (P < .001 for trend). Similar
      relative risks were noted for Adult Treatment Panel III clinical cut points and
      after the exclusion of obese or diabetic women. CONCLUSION: In this large
      prospective cohort, atherogenic dyslipidemias were associated with the subsequent
      development of hypertension among healthy women.

PMID- 16287775
TI  - The relation between p70S6k expression in lymphocytes and the decline of
      cognitive test scores in patients with Alzheimer disease.

PMID- 16287776
TI  - Female sex as a possible protective factor from myocardial involvement in
      transthyretin-related amyloidoses.

PMID- 16287777
TI  - Bleeding complications in elderly patients following acute myocardial infarction.

PMID- 16287778
TI  - Out-of-pocket prescription costs: a suggestion.

PMID- 16287779
TI  - Prevalence of successful weight loss.

PMID- 16287781
TI  - Sex, not just race.

PMID- 16287780
TI  - The other side of the bezafibrate infarction prevention trial data.

PMID- 16287782
TI  - Dairy intake, reduced body iron stores, and the development of type 2 diabetes
      mellitus.

PMID- 16287783
TI  - Dairy and type 2 diabetes mellitus: wrong conclusions.

PMID- 16287784
TI  - Dairy, vitamin D, and type 2 diabetes mellitus.

PMID- 16287785
TI  - Summaries for patients. Evaluating the risk for pregnancy-associated venous
      thromboembolism: a 30-year study.

PMID- 16287786
TI  - Summaries for patients. Condom use and genital herpes.

PMID- 16287787
TI  - Summaries for patients. Neuropsychological side effects of efavirenz.

PMID- 16287788
TI  - Summaries for patients. The metabolic syndrome and fatty liver disease.

PMID- 16287789
TI  - Summaries for patients. Quality of HIV health care provided by nurse
      practitioners, physician assistants, and doctors.

PMID- 16287790
TI  - Trends in the incidence of venous thromboembolism during pregnancy or postpartum:
      a 30-year population-based study.
AB  - BACKGROUND: The risk for venous thromboembolism during pregnancy or postpartum is
      uncertain. OBJECTIVES: To estimate the relative and absolute risk for deep venous
      thrombosis and pulmonary embolism during pregnancy and postpartum and to describe
      trends in incidence. DESIGN: Population-based inception cohort study using the
      resources of the Rochester Epidemiology Project. SETTING: Olmsted County,
      Minnesota. PATIENTS: Women with deep venous thrombosis or pulmonary embolism
      first diagnosed between 1966 and 1995, including women with venous
      thromboembolism during pregnancy or the postpartum period (defined as delivery of
      a newborn no more than 3 months before the deep venous thrombosis or pulmonary
      embolism event date, including delivery of a stillborn infant after the first
      trimester). MEASUREMENTS: The authors obtained yearly counts of live births in
      Olmsted County between 1966 and 1995 from the Minnesota Department of Health.
      RESULTS: The relative risk (standardized incidence ratio) for venous
      thromboembolism among pregnant or postpartum women was 4.29 (95% CI, 3.49 to
      5.22;P < 0.001), and the overall incidence of venous thromboembolism (absolute
      risk) was 199.7 per 100,000 woman-years. The annual incidence was 5 times higher
      among postpartum women than pregnant women (511.2 vs. 95.8 per 100,000), and the
      incidence of deep venous thrombosis was 3 times higher than that of pulmonary
      embolism (151.8 vs. 47.9 per 100,000). Pulmonary embolism was relatively uncommon
      during pregnancy versus the postpartum period (10.6 vs. 159.7 per 100,000). Over
      the 30-year study period, the incidence of venous thromboembolism during
      pregnancy remained relatively constant whereas the postpartum incidence of
      pulmonary embolism decreased more than 2-fold. LIMITATIONS: Because the Olmsted
      County population was 98% white and of non-Hispanic ethnicity, the results may
      not be generalizable to other ethnicities. CONCLUSIONS: Among pregnant women, the
      highest risk period for venous thromboembolism and pulmonary embolism in
      particular is during the postpartum period. Any prophylaxis against these events
      should be particularly targeted to postpartum women. Although the incidence of
      pulmonary embolism has decreased over time, the incidence of deep venous
      thrombosis remains unchanged, indicating the need to better identify pregnant
      women at increased risk.

PMID- 16287791
TI  - The relationship between condom use and herpes simplex virus acquisition.
AB  - BACKGROUND: Few studies have evaluated the relationship between condom use and
      herpes simplex virus type 2 (HSV-2) and HSV type 1 (HSV-1) acquisition.
      OBJECTIVE: To assess the relationship between condom use and acquisition of HSV-2
      and HSV-1 among men and women. DESIGN: Analysis of data collected as part of a
      clinical trial of an ineffective candidate vaccine for HSV-2. SETTING: Sexually
      transmitted disease clinics. PARTICIPANTS: Men and women at risk for HSV-2
      acquisition, defined as having 4 or more sexual partners or having a sexually
      transmitted disease in the past year. MEASUREMENT: Acquisition of HSV-2 and HSV-1
      as measured by viral culture or change to positive HSV serostatus. RESULTS: Of
      1843 participants, 118 (6.4%) became infected with HSV-2. In multivariate
      analyses, participants reporting more frequent use of condoms were at lower risk
      for acquiring HSV-2 than participants who used condoms less frequently (hazard
      ratio, 0.74 [95% CI, 0.59 to 0.95]); categories of increasing condom use were 0%
      to 25%, 25% to 75%, and greater than 75% of sexual acts. Nineteen (2.9%) of 659
      participants at risk for infection with HSV-1 became infected. No statistically
      significant association between condom use and infection with HSV-1 was found
      (hazard ratio, 0.79 [CI, 0.48 to 1.31]). LIMITATIONS: Use of condoms was measured
      by self-report, and persons who used condoms may have differed from those who did
      not. CONCLUSIONS: Consistent use of condoms is associated with lower rates of
      infection with HSV-2 and should be routinely recommended.

PMID- 16287794
TI  - Quality of HIV care provided by nurse practitioners, physician assistants, and
      physicians.
AB  - BACKGROUND: Nurse practitioners (NPs) and physician assistants (PAs) are primary
      care providers for patients with HIV in some clinics, but little is known about
      the quality of care that they provide. OBJECTIVE: To compare the quality of care
      provided by NPs and PAs with that provided by physicians. DESIGN: Cross-sectional
      analysis. SETTING: 68 HIV care sites, funded by Ryan White Comprehensive AIDS
      Resources Emergency (CARE) Act Title III, in 30 different states. PARTICIPANTS:
      The authors surveyed 243 clinicians (177 physicians and 66 NPs and PAs) and
      reviewed medical records of 6651 persons with HIV or AIDS. MEASUREMENTS: 8
      quality-of-care measures assessed by medical record review. RESULTS: After
      adjustments for patient characteristics, 6 of the 8 quality measures did not
      statistically significantly differ between NPs and PAs and either infectious
      disease specialists or generalist HIV experts. Adjusted rates of purified protein
      derivative testing and Papanicolaou smears were statistically significantly
      higher for NPs and PAs (0.63 and 0.71, respectively) than for infectious disease
      specialists (0.53 [P = 0.007] and 0.56 [P = 0.001], respectively) or generalist
      HIV experts (0.47 [P < 0.001] and 0.62 [P = 0.025], respectively). Nurse
      practitioners and PAs had statistically significantly higher performance scores
      than generalist non-HIV experts on 6 of the 8 quality measures. LIMITATIONS:
      These results may not be generalizable to care settings where on-site physician
      HIV experts are not accessible or to measures of more complex clinical processes.
      CONCLUSIONS: For the measures examined, the quality of HIV care provided by NPs
      and PAs was similar to that of physician HIV experts and generally better than
      physician non-HIV experts. Nurse practitioners and PAs can provide high-quality
      care for persons with HIV. Preconditions for this level of performance include
      high levels of experience, focus on a single condition, and either participation
      in teams or other easy access to physicians and other clinicians with HIV
      expertise.

PMID- 16287793
TI  - The metabolic syndrome as a predictor of nonalcoholic fatty liver disease.
AB  - BACKGROUND: The frequent association of nonalcoholic fatty liver disease with
      components of the metabolic syndrome such as obesity, hyperglycemia,
      dyslipidemia, and hypertension is well known. However, no prospective study has
      examined the role of the metabolic syndrome in the development of this disease.
      OBJECTIVE: To characterize the longitudinal relationship between the metabolic
      syndrome and nonalcoholic fatty liver disease. DESIGN: A prospective
      observational study. SETTING: A medical health checkup program in a general
      hospital. PARTICIPANTS: 4401 apparently healthy Japanese men and women, 21 to 80
      years of age, with a mean body mass index (BMI) of 22.6 kg/m2 (SD, 3.0).
      MEASUREMENTS: Alcohol intake was assessed by using a questionnaire. Biochemical
      tests for liver and metabolic function and abdominal ultrasonography were done.
      Modified criteria of the National Cholesterol Education Program Adult Treatment
      Panel III were used to characterize the metabolic syndrome. RESULTS: At baseline,
      812 of 4401 (18%) participants had nonalcoholic fatty liver disease. During the
      mean follow-up period of 414 days (SD, 128), the authors observed 308 new cases
      (10%) of nonalcoholic fatty liver disease among 3147 participants who were
      disease-free at baseline and who completed a second examination. Regression of
      nonalcoholic fatty liver disease was found in 113 (16%) of 704 participants who
      had the disease at baseline and who completed a second examination. Men and women
      who met the criteria for the metabolic syndrome at baseline were more likely to
      develop the disease during follow-up (adjusted odds ratio, 4.00 [95% CI, 2.63 to
      6.08] and 11.20 [CI, 4.85 to 25.87], respectively). Nonalcoholic fatty liver
      disease was less likely to regress in those participants with the metabolic
      syndrome at baseline. LIMITATIONS: Ultrasonography may lead to an incorrect
      diagnosis of nonalcoholic fatty liver disease in 10% to 30% of cases and cannot
      distinguish steatohepatitis from simple steatosis. Self-reported alcohol intake
      may cause bias. Because all of the participants were Japanese, generalizability
      to non-Japanese populations is uncertain. CONCLUSIONS: The metabolic syndrome is
      a strong predictor of nonalcoholic fatty liver disease.

PMID- 16287792
TI  - Impact of efavirenz on neuropsychological performance and symptoms in HIV
      infected individuals.
AB  - BACKGROUND: Efavirenz is a commonly used antiretroviral drug that causes
      neurologic side effects in more than 50% of patients. OBJECTIVE: To characterize
      efavirenz-associated neurologic symptoms in a randomized, controlled study of
      initial antiretroviral treatment. DESIGN: Substudy of a randomized, double-blind,
      controlled trial of combination antiretroviral regimens (A5095) that was
      performed between March 2001 and January 2002. SETTING: Multicenter academic
      clinical trial units. PARTICIPANTS: HIV-infected patients who were initiating
      therapy in the context of a controlled trial. MEASUREMENTS: Neuropsychological
      performance measures, including the Digit Symbol Substitution Test and the Trail
      Making Test (Parts A and B); symptom questionnaires; standardized assessments of
      sleep quality, anxiety, and depression; and efavirenz plasma concentrations.
      RESULTS: Twenty of 303 (6.6%) enrolled participants prematurely discontinued the
      study. Neuropsychological performance improved in both groups over time without
      significant differences between patients who were receiving efavirenz and those
      who were not. The efavirenz group experienced more neurologic symptoms at week 1
      (P < 0.001) but not at weeks 4, 12, or 24. A sleep index revealed that
      participants receiving efavirenz had more "bad dreams" during the first week of
      therapy (P = 0.038). No significant changes in anxiety or depressed mood were
      noted. Changes in efavirenz-associated neurologic symptoms were correlated to
      efavirenz plasma concentrations at week 1 but not at later time points. Twelve
      (6%) patients receiving efavirenz stopped taking the drug before the end of the
      study because of central nervous system symptoms. LIMITATIONS: Participant
      selection may have been biased in favor of patients with fewer psychiatric
      complications. The study design permitted substitution of a new drug in place of
      efavirenz in cases of treatment-limiting toxicity. CONCLUSIONS: In a large
      controlled trial, efavirenz use was associated with neurologic symptoms distinct
      from depression and anxiety that began early in therapy but resolved by week 4.
      Improvement in neuropsychological performance was comparable in patients who were
      receiving efavirenz and those who were not.

PMID- 16287795
TI  - Update in cardiology.

PMID- 16287796
TI  - The Terri Schiavo case: legal, ethical, and medical perspectives.
AB  - Although tragic, the plight of Terri Schiavo provides a valuable case study. The
      conflicts and misunderstandings surrounding her situation offer important lessons
      in medicine, law, and ethics. Despite media saturation and intense public
      interest, widespread confusion lingers regarding the diagnosis of persistent
      vegetative state, the judicial processes involved, and the appropriateness of the
      ethical framework used by those entrusted with Terri Schiavo's care. First, the
      authors review the current medical understanding of persistent vegetative state,
      including the requirements for patient examination, the differential diagnosis,
      and the practice guidelines of the American Academy of Neurology regarding
      artificial nutrition and hydration for patients with this diagnosis. Second, they
      examine the legal history, including the 2000 trial, the 2002 evidentiary
      hearing, and the subsequent appeals. The authors argue that the law did not fail
      Terri Schiavo, but produced the highest-quality evidence and provided the most
      judicial review of any end-of-life guardianship case in U.S. history. Third, they
      review alternative ethical frameworks for understanding the Terri Schiavo case
      and contend that the principle of respect for autonomy is paramount in this case
      and in similar cases. Far from being unusual, the manner in which Terri Schiavo's
      case was reviewed and the basis for the decision reflect a broad medical, legal,
      and ethical consensus. Greater clarity regarding the persistent vegetative state,
      less apprehension of the presumed mysteries of legal proceedings, and greater
      appreciation of the ethical principles at work are the chief benefits obtained
      from studying this provocative case.

PMID- 16287797
TI  - Thromboembolism in pregnancy: a continuing conundrum.

PMID- 16287798
TI  - An ounce of prevention.

PMID- 16287799
TI  - Dangerous liaisons: the metabolic syndrome and nonalcoholic fatty liver disease.

PMID- 16287800
TI  - Looking for Betty.

PMID- 16287801
TI  - Advanced lipoprotein testing in young adults.

PMID- 16287802
TI  - Preventing sudden cardiac death.

PMID- 16287803
TI  - Cost-effectiveness in hepatitis B.

PMID- 16287804
TI  - Outlier status of U.S. health care costs.

PMID- 16287805
TI  - Outlier status of U.S. health care costs.

PMID- 16287806
TI  - The New York case: lessons being learned.

PMID- 16287807
TI  - Immune thrombocytopenia associated with efalizumab therapy for psoriasis.

PMID- 16287808
TI  - Patient-to-patient transmission of hepatitis C.

PMID- 16287809
TI  - Sibutramine use associated with reversible hepatotoxicity.

PMID- 16287810
TI  - Bradycardia and edema in a patient receiving herbal therapy for fertility.

PMID- 16287811
TI  - "What else?" Setting the agenda for the clinical interview.

PMID- 16287812
TI  - Why prion diseases are a mystery, and why they matter.

PMID- 16287813
TI  - Centaurin-alpha1 is a phosphatidylinositol 3-kinase-dependent activator of ERK1/2
      mitogen-activated protein kinases.
AB  - Centaurin-alpha1 is known to be a phosphatidylinositol 3,4,5-triphosphate (PIP3)
      binding protein that has two pleckstrin homology domains and a putative ADP
      ribosylation factor GTPase-activating protein domain. However, the physiological
      function of centaurin-alpha1 is still not understood. Here we have shown that
      transient expression of centaurin-alpha1 in COS-7 cells results in specific
      activation of ERK, and the activation is inhibited by co-expression of a dominant
      negative form of Ras. We have also found that a mutant form of centaurin-alpha1
      that is unable to bind PIP3 fails to induce ERK activation and that a
      phosphatidylinositol 3-kinase inhibitor LY294002 inhibits centaurin-alpha1
      dependent ERK activation. Furthermore, transient knockdown of centaurin-alpha1 by
      small interfering RNAs results in reduced ERK activation after epidermal growth
      factor stimulation in T-REx 293 cells. These results suggest that centaurin
      alpha1 contributes to ERK activation in growth factor signaling, linking the PI3K
      pathway to the ERK mitogen-activated protein kinase pathway through its ability
      to interact with PIP3.

PMID- 16287815
TI  - Clinical application of the 15-minute family interview: addressing the needs of
      postpartum families.
AB  - The purpose of this article is to describe the application of the 15-minute
      family interview to family-centered nursing practice on a postpartum unit. Guided
      by the five key components of the 15-minute family interview (manners,
      therapeutic conversation, genogram or ecomap, therapeutic questions, and
      commendations), clinical excerpts of interviews with families illustrate
      application to practice. The 15-minute family interview is not a strategic,
      decontextual nursing tool; rather, it is a flexible interview guide that is
      embedded in family nursing practice, in the relationship between the nurse and
      family and in the nurse's philosophical assumptions and obligations to do well by
      families.

PMID- 16287814
TI  - Theoretical study of the Hoogsteen-Watson-Crick junctions in DNA.
AB  - A series of d (AT)(n) oligonucleotides containing mixtures of normal B-type
      Watson-Crick and antiparallel Hoogsteen helices have been studied using molecular
      dynamics simulation techniques to analyze the structural and thermodynamic impact
      of the junction between Watson-Crick and antiparallel Hoogsteen structures.
      Analysis of molecular dynamics simulations strongly suggests that for all
      oligonucleotides studied the antiparallel Hoogsteen appears as a reasonable
      conformation, only slightly less stable than the canonical B-type Watson-Crick
      one. The junctions between the Watson-Crick and Hoogsteen structures introduces a
      priori a sharp discontinuity in the helix, because the properties of each type of
      conformation are very well preserved in the corresponding fragments. However, and
      quite counterintuitively, junctions do not largely distort the duplex in
      structural, dynamics or energetic terms. Our results strongly support the
      possibility that small fragments of antiparallel Hoogsteen duplex might be
      embedded into large fragments of B-type Watson-Crick helices, making possible
      protein-DNA interactions that are specific of the antiparallel Hoogsteen
      conformation.

PMID- 16287816
TI  - Assessing the quality of the dyadic relationship in first-time parents:
      development of a new instrument.
AB  - The purpose of this research was to psychometrically evaluate the Dyadic
      Adjustment Scale (DAS), modified for use with new, first-time parents by
      extending the items of communication, sensuality, and sexuality. A total of 820
      Swedish respondents, 6 months after the birth of their first child, participated
      in the study. Psychometric evaluation was conducted with factor analysis. The
      obtained factor structure was tested with multitrait analysis program. Thirty
      three items were found to fit into a five-factor solution, explaining 50% of the
      total variance. Descriptive data revealed that most new parents were satisfied
      with their intimate relationship in general, but dissatisfied with their sexual
      lives. The modified DAS, now called the Quality of Dyadic Relationship Instrument
      includes 33 items and seems to be a useful, updated measurement for assessing
      quality of the intimate relationship in new first-time parents.

PMID- 16287817
TI  - Development of professional practice based on a family systems nursing framework:
      nurses' and families' experiences.
AB  - The purpose of this evaluation project was to elicit nurses'and families'
      experiences about differences and changes for nurses and families and the family
      nurse relationship when a family systems nursing approach was used to guide
      practice. Following nurses' involvement in an educational workshop, the
      evaluation examined changes in nurses'and families' experiences over an 8-week
      period of a child's hospitalization in a pediatric rehabilitation center. A total
      of 17 nurses and 13 parents participated in the project. Nurses and parents
      completed questionnaires and participated in semi-structured interviews and focus
      groups. Nurses completed journals reflecting on their interactions with families.
      Data were analyzed using descriptive statistics and content analysis. Findings
      indicate that a family systems nursing approach had a positive impact on how
      nurses viewed their nursing practice and their work with families, thereby
      enhancing family-nurse relationships. Such findings have relevance to clinical
      nursing practice, professional development, and evaluation research design.

PMID- 16287818
TI  - The search for social safety and comfort in families raising children with
      complex chronic conditions.
AB  - Social consequences of raising children who were medically fragile and
      developmentally delayed (MF/DD) were explored in an ethnographic study of 20
      families with school-age children. The overarching theme was the families' search
      for safety and comfort in social situations. Major categories comprising this
      theme included the need to anticipate and plan for the child's care; overcoming
      environmental, child-related, and attitudinal barriers; and finding social
      activities that were comfortable for all members of the family. When this search
      was successful, families could relax, and all members could participate in a
      variety of social encounters and activities; but when safety and comfort could
      not be achieved, families were likely to limit social activities or split the
      family so that the child who was MF/DD could be cared for while other family
      members participated in social events.

PMID- 16287819
TI  - Family health care across cultures: an international online program.

PMID- 16287820
TI  - The three most common errors in family nursing: how to avoid or sidestep.
AB  - In this article, the authors offer what they believe to be the three most common
      errors or mistakes in relational family nursing practice. Each error is
      described, followed by practical suggestions on how the mistake or error can be
      avoided. A clinical case vignette for each error is also given, with useful ideas
      of how the mistakes could have been avoided or sidestepped. By sidestepping and
      avoiding the most prevalent mistakes, nurses can not only sustain but also
      improve their nursing care of families and thus prevent unnecessary anguish and
      suffering of family members and possible shame, guilt, or embarrassment on the
      part of the nurse.

PMID- 16287821
TI  - Adolescents with type 1 diabetes: family functioning and metabolic control.
AB  - Families play central roles in the care of their adolescents with chronic
      illnesses. This study examined the relationship between family functioning and
      metabolic control in adolescents with Type 1 diabetes. The McMaster Family
      Assessment Device (FAD) measured family functioning; the Youth Self-Report Form
      (YSR) measured adolescent behavior. Older adolescents reported increased family
      dysfunction. Adolescents who reported family dysfunction on affective
      responsiveness had HbA(1c) levels greater than 9. Older adolescents, males, and
      adolescents who reported a greater number of behavior problems were significantly
      more likely to have HbA(1c) levels greater than 9. Considered together, older age
      and greater attention problems were most significantly associated with higher
      HbA(1c) levels. These findings suggest the importance of the relationship between
      the adolescent's perception of family functioning and metabolic control in the
      adolescents with Type 1 diabetes.

PMID- 16287823
TI  - Canadian families caring for members with mental illness: a vicious cycle.
AB  - The purpose of this qualitative, descriptive study was to explore the
      perspectives of individuals who were caring for a family member with a mental
      illness, with particular attention to housing, quality of supports, and formal
      care services. Eleven focus groups with family caregivers (N = 75) were
      conducted. Both individual and team thematic analyses were undertaken until
      interpretations of the experiences of the participants were inductively developed
      and conceptualized into a holistic interpretation. Findings revealed that family
      caregivers were part of a "circle of care," supporting the independence of the
      individual with mental illness while attempting to protect their family member
      with mental illness. However, findings suggested that this circle of care led to
      a "vicious cycle" of caregiving. Three major themes were identified: witnessing
      inadequacies, working behind the scenes, and creating a better world. Health
      promoting family nursing practice and policy implications, as well as areas for
      further research, are discussed.

PMID- 16287822
TI  - Heterosocial behaviors in early adolescent African American girls: the role of
      mother-daughter relationships.
AB  - Recent epidemiological trends in HIV/AIDS have helped draw attention to minority
      adolescents as especially high risk for HIV acquisition. Research shows the
      importance of maternal-child closeness and sexual communication in decreasing
      adolescent risk behaviors. The information, motivation, behavioral skills model
      (IMB) formed the framework for this pilot study whose purpose was to examine the
      informational and motivational antecedents of heterosocial risks in African
      American middle-school-aged girls and the maternal influence on these risks.
      Thirty-nine mother-daughter dyads participated, of whom 54% were impoverished.
      The girls' intent to stay safe, perceived social norms, and closeness to mother
      were negatively correlated with reported participation in potentially risky
      situations. Early interventions may enhance mother-daughter bonding, increasing
      sexual communication, and decreasing girls' participation in risky behaviors.
      This pilot study provides direction regarding testing of the IMB model in studies
      focused on early adolescent behaviors and mother-daughter interactions.

PMID- 16287824
TI  - Crossing community sectors: challenges faced by families of children with special
      health care needs.
AB  - This article identifies unmet needs and challenges of 37 families caring for
      children with special health care needs (CSHCN). Data were collected in focus
      groups. Data saturation occurred in the third group. Another group was conducted
      to ensure adequate inclusion of rural participants. Mean age of participants was
      36 years. Most participants were women (92%), Caucasian (65%), high school
      graduates (89%), and employed, with 38% from rural communities. All families had
      health care insurance, primarily Medicaid (87%). An interdisciplinary team used
      NVIVO software to facilitate content analysis. Seven areas emerged: family
      support systems, early intervention/school systems, coordination of care, lack of
      knowledge, provider/family relationships, parent roles, and insurance systems.
      Caregivers noted the critical role of nurses but a lack of nurse presence in
      community care systems. This study adds to the multidimensional nature of caring
      for CSHCN and highlights the importance of considering how families interface
      with multiple community sectors.

PMID- 16287826
TI  - Beliefs about the controllability of pain: congruence between older adults with
      cancer and their family caregivers.
AB  - Family dyadic beliefs about pain controllability were examined to determine what
      influence they had on patient symptom distress and subjective caregiver burden.
      The Calgary Family Assessment and Intervention Models and Illness Beliefs Model
      guided this investigation. Self-report questionnaires were administered to a
      sample of 81 family dyads that consisted of ambulatory cancer care older adult
      outpatients and their family caregivers. Inferential statistics indicated that
      family dyads were congruent in their beliefs about pain controllability.
      Descriptive statistics showed that family dyads with beliefs that the pain was
      controllable had less symptom distress and caregiver burden than dyads with
      beliefs that pain was not controllable. Results suggest that family dyadic
      beliefs that cancer-related pain is controllable have a positive influence on
      family pain control outcomes. Findings also support the need for nurses to
      include family members when developing pain management interventions for older
      adults.

PMID- 16287825
TI  - Families' experiences of support provided by resource-oriented family
      professionals in Finland.
AB  - This study describes the support provided by resource-oriented family workers in
      Finland and the prerequisites for such support. Family workers consisted of
      professionals such as public health nurses, nurses, social educators,
      psychologists, kindergarten teachers, and social workers. The overall research
      project consisted of four separate studies carried out within the Families With
      Children Project. The findings of the four studies were aggregated and submitted
      to a secondary analysis. Interview data from 51 parents across 44 families with
      young children were included in the analysis. The families reported that they
      received emotional, cognitive, instrumental, and community and network support
      from the family workers. The work of resource-oriented family professionals was
      facilitated by the arrangements and orientation of the service model and by the
      quality of interaction between the family worker and the family. The families'
      experiences of support underlined the multiple dimensions of the cooperative
      relationship and the usefulness of the supportive interaction. The findings
      extend the understanding of resource-oriented family work from the perspective of
      families and offer important implications for the caring of families with young
      children.

PMID- 16287827
TI  - The influence of family on immigrant South Asian women's health.
AB  - The purpose of this study was to examine the influence of family members on
      immigrant South Asian women's health and health-seeking behavior. This
      qualitative study was part of a larger study that examined the health-seeking
      practices of immigrant South Asian women living in the Lower Mainland of British
      Columbia, Canada. Using ethnographic methods, data were collected through face-to
      face interviews with women who had lived in Canada for 10 months to 31 years.
      Analysis of translated and transcribed data revealed that women made decisions
      about their health in consultation with family members. Overall, family members
      were perceived to be supportive and provided direct and indirect assistance to
      women in ways that influenced their health. Expected roles and responsibilities
      often had detrimental influences on women's health. Health care for immigrant
      South Asian women needs to take into account women's relationships with family
      members and the influence of family on women's health.

PMID- 16287828
TI  - Service needs of families with children with ADHD.
AB  - This article describes service use, perceived helpfulness of services, and the
      services requested of 157 families living with a child or adolescent with
      attention-deficit/hyperactivity disorder (ADHD) and specifically asks if service
      use and service need is a function of certain social demographic factors. Whereas
      these data suggest that ADHD is a fairly universal experience, as indicated by
      the high rate of service use across ethnic groups, income status, sex, and family
      composition, single-mother families used the most services, Hispanic families
      used the fewest, and families with boys with ADHD used more services than
      families with girls with ADHD. Income was not a significant factor in any
      services used or services requested. This study lends strength to the argument
      that more specialized services for certain groups are needed in venues with local
      community services, such as schools, where the majority of these children and
      families are already seeking help.

PMID- 16287830
TI  - Family nursing: challenges and opportunities: providing leadership in family
      nursing from local to global health.

PMID- 16287829
TI  - A preliminary investigation of the grandparent support scale for teenage mothers.
AB  - Although numerous instruments are available to assess the teen mother's social
      support, an instrument that is more narrowly focused on the support teen mothers
      receive from their parents (the grandparents) is lacking. To remedy this gap, the
      Grandparent Support Scale for Teenage Mothers (GSSTM) was developed. The purpose
      of this article is to review what is known about grandparent support and describe
      the initial psychometric testing of the teen version of the GSSTM. Four
      questionnaires were completed by 72 teen mothers. Factor analysis of the GSSTM
      resulted in reduction of the questionnaire from 22 to 16 items and yielded three
      factors: Grandparent Responsiveness (alpha = .90), Grandparent as Decision Maker
      (alpha = .76), and Grandparent as Actor (alpha = .72). GSSTM subscales
      significantly correlated with the other measures, supporting their validity.
      Although further psychometric testing is needed with a larger sample, the GSSTM
      shows promise in assessing teen mothers' perceptions of family support.

PMID- 16287832
TI  - Family nursing: challenges and opportunities: whither thou goeth family nursing.

PMID- 16287831
TI  - Family nursing: challenges and opportunities: what will the challenges for family
      nursing be over the next few years?

PMID- 16287833
TI  - Family nursing: challenges and opportunities: the hand that feeds us: strings and
      restrictions on funding for family nursing research.

PMID- 16287835
TI  - Family nursing: challenges and opportunities: the challenge and opportunity of
      complex uncertainty.

PMID- 16287834
TI  - Family nursing: challenges and opportunities: marriage: it matters in sickness
      and in health.

PMID- 16287836
TI  - Ethos, ethics, and endeavors: new horizons in family nursing.
AB  - This article is an invitation to contemplation and dialogue about the purpose of
      family nursing. The shared ethos of family nursing is explored as a common ground
      for endeavours in practice and research. A comparison of ethical principles
      relating to research, family nursing practice, and Foucault's meta-ethical
      framework is offered. Such examination would suggest a remarkable congruence
      between family nursing values and Foucault's meta-ethical framework. The
      implications of such theoretical deliberations are outlined within the context of
      contemporary issues at a global level. Further support for the relevance of the
      implications at national level is presented by drawing on examples of challenges
      for nursing work with families in primary care in the United Kingdom. This
      article also raises new questions based on a number of suppositions such as
      family nursing being conceptualized as relational practice with an integrated
      approach, unifying ethos, and potential of a new paradigm of care.

PMID- 16287837
TI  - Nursing science and chronic illness: articulating suffering and possibility in
      family life.
AB  - Families living with a member who has a chronic illness vacillate between hope
      and despair, suffering and possibility. How this living "between" evolves in
      families and how family relations are affected has received insufficient
      attention. As nurses we can learn families' experiences of suffering and situated
      possibility through family narratives about and reflections on the everyday.
      Articulating this experience in thick, alive, complex, and practical texts
      promises to enhance our understanding, our practice with families, and our own
      lived possibilities.

PMID- 16287838
TI  - Going home: formerly incarcerated African American men return to families and
      communities.
AB  - More than 800,000 African American men are currently incarcerated in prisons or
      jails in the United States. Most of these men leave prison ill prepared to return
      to society as workers, or to reintegrate into family settings. Returning from
      prison is complicated by struggles in the housing and job markets. This article
      begins with a review of literature exploring drug laws and disproportionate
      incarceration rates, homelessness, and joblessness. Data from a community-based,
      qualitative study of African American men following incarceration is presented. A
      discussion of how incarceration influenced their return to family situations is
      included that supports the findings by earlier studies on the effects of
      homelessness and joblessness on individuals and families. The article concludes
      with recommendations for the development of targeted support systems and offers
      suggestions for future nursing research with this population.

PMID- 16287839
TI  - The hematopoietic transcription factor AML1 (RUNX1) is negatively regulated by
      the cell cycle protein cyclin D3.
AB  - The family of cyclin D proteins plays a crucial role in the early events of the
      mammalian cell cycle. Recent studies have revealed the involvement of AML1
      transactivation activity in promoting cell cycle progression through the
      induction of cyclin D proteins. This information in combination with our previous
      observation that a region in AML1 between amino acids 213 and 289 is important
      for its function led us to investigate prospective proteins associating with this
      region. We identified cyclin D3 by a yeast two-hybrid screen and detected AML1
      interaction with the cyclin D family by both in vitro pull-down and in vivo
      coimmunoprecipitation assays. Furthermore, we demonstrate that cyclin D3
      negatively regulates the transactivation activity of AML1 in a dose-dependent
      manner by competing with CBFbeta for AML1 association, leading to a decreased
      binding affinity of AML1 for its target DNA sequence. AML1 and its fusion protein
      AML1-ETO have been shown to shorten and prolong the mammalian cell cycle,
      respectively. In addition, AML1 promotes myeloid cell differentiation. Thus, our
      observations suggest that the direct association of cyclin D3 with AML1 functions
      as a putative feedback mechanism to regulate cell cycle progression and
      differentiation.

PMID- 16287840
TI  - Dual regulation of c-Myc by p300 via acetylation-dependent control of Myc protein
      turnover and coactivation of Myc-induced transcription.
AB  - The c-Myc oncoprotein (Myc) controls cell fate by regulating gene transcription
      in association with a DNA-binding partner, Max. While Max lacks a transcription
      regulatory domain, the N terminus of Myc contains a transcription activation
      domain (TAD) that recruits cofactor complexes containing the histone
      acetyltransferases (HATs) GCN5 and Tip60. Here, we report a novel functional
      interaction between Myc TAD and the p300 coactivator-acetyltransferase. We show
      that p300 associates with Myc in mammalian cells and in vitro through direct
      interactions with Myc TAD residues 1 to 110 and acetylates Myc in a TAD-dependent
      manner in vivo at several lysine residues located between the TAD and DNA-binding
      domain. Moreover, the Myc:Max complex is differentially acetylated by p300 and
      GCN5 and is not acetylated by Tip60 in vitro, suggesting distinct functions for
      these acetyltransferases. Whereas p300 and CBP can stabilize Myc independently of
      acetylation, p300-mediated acetylation results in increased Myc turnover. In
      addition, p300 functions as a coactivator that is recruited by Myc to the
      promoter of the human telomerase reverse transcriptase gene, and p300/CBP
      stimulates Myc TAD-dependent transcription in a HAT domain-dependent manner. Our
      results suggest dual roles for p300/CBP in Myc regulation: as a Myc coactivator
      that stabilizes Myc and as an inducer of Myc instability via direct Myc
      acetylation.

PMID- 16287841
TI  - ETO-2 associates with SCL in erythroid cells and megakaryocytes and provides
      repressor functions in erythropoiesis.
AB  - Lineage specification and cellular maturation require coordinated regulation of
      gene expression programs. In large part, this is dependent on the activator and
      repressor functions of protein complexes associated with tissue-specific
      transcriptional regulators. In this study, we have used a proteomic approach to
      characterize multiprotein complexes containing the key hematopoietic regulator
      SCL in erythroid and megakaryocytic cell lines. One of the novel SCL-interacting
      proteins identified in both cell types is the transcriptional corepressor ETO-2.
      Interaction between endogenous proteins was confirmed in primary cells. We then
      showed that SCL complexes are shared but also significantly differ in the two
      cell types. Importantly, SCL/ETO-2 interacts with another corepressor, Gfi-1b, in
      red cells but not megakaryocytes. The SCL/ETO-2/Gfi-1b association is lost during
      erythroid differentiation of primary fetal liver cells. Genetic studies of
      erythroid cells show that ETO-2 exerts a repressor effect on SCL target genes. We
      suggest that, through its association with SCL, ETO-2 represses gene expression
      in the early stages of erythroid differentiation and that alleviation/modulation
      of the repressive state is then required for expression of genes necessary for
      terminal erythroid maturation to proceed.

PMID- 16287842
TI  - The iStem, a long-range RNA secondary structure element required for efficient
      exon inclusion in the Drosophila Dscam pre-mRNA.
AB  - The Drosophila Dscam gene encodes 38,016 different proteins, due to alternative
      splicing of 95 of its 115 exons, that function in axon guidance and innate
      immunity. The alternative exons are organized into four clusters, and the exons
      within each cluster are spliced in a mutually exclusive manner. Here we describe
      an evolutionarily conserved RNA secondary structure we call the Inclusion Stem
      (iStem) that is required for efficient inclusion of all 12 variable exons in the
      exon 4 cluster. Although the iStem governs inclusion or exclusion of the entire
      exon 4 cluster, it does not play a significant role in determining which variable
      exon is selected. Thus, the iStem is a novel type of regulatory element that
      simultaneously controls the splicing of multiple alternative exons.

PMID- 16287843
TI  - Muscle-specific loss of apoptosis-inducing factor leads to mitochondrial
      dysfunction, skeletal muscle atrophy, and dilated cardiomyopathy.
AB  - Cardiac and skeletal muscle critically depend on mitochondrial energy metabolism
      for their normal function. Recently, we showed that apoptosis-inducing factor
      (AIF), a mitochondrial protein implicated in programmed cell death, plays a role
      in mitochondrial respiration. However, the in vivo consequences of AIF-regulated
      mitochondrial respiration resulting from a loss-of-function mutation in Aif are
      not known. Here, we report tissue-specific deletion of Aif in the mouse. Mice in
      which Aif has been inactivated specifically in cardiac and skeletal muscle
      exhibit impaired activity and protein expression of respiratory chain complex I.
      Mutant animals develop severe dilated cardiomyopathy, heart failure, and skeletal
      muscle atrophy accompanied by lactic acidemia consistent with defects in the
      mitochondrial respiratory chain. Isolated hearts from mutant animals exhibit poor
      contractile performance in response to a respiratory chain-dependent energy
      substrate, but not in response to glucose, supporting the notion that impaired
      heart function in mutant animals results from defective mitochondrial energy
      metabolism. These data provide genetic proof that the previously defined cell
      death promoter AIF has a second essential function in mitochondrial respiration
      and aerobic energy metabolism required for normal heart function and skeletal
      muscle homeostasis.

PMID- 16287844
TI  - Loss of SOD1 and LYS7 sensitizes Saccharomyces cerevisiae to hydroxyurea and DNA
      damage agents and downregulates MEC1 pathway effectors.
AB  - Aerobic metabolism produces reactive oxygen species, including superoxide anions,
      which cause DNA damage unless removed by scavengers such as superoxide
      dismutases. We show that loss of the Cu,Zn-dependent superoxide dismutase, SOD1,
      or its copper chaperone, LYS7, confers oxygen-dependent sensitivity to
      replication arrest and DNA damage in Saccharomyces cerevisiae. We also find that
      sod1Delta strains, and to a lesser extent lys7Delta strains, when arrested with
      hydroxyurea (HU) show reduced induction of the MEC1 pathway effector Rnr3p and of
      Hug1p. The HU sensitivity of sod1Delta and lys7Delta strains is suppressed by
      overexpression of TKL1, a transketolase that generates NADPH, which balances
      redox in the cell and is required for ribonucleotide reductase activity. Our
      results suggest that the MEC1 pathway in sod1Delta mutant strains is sensitive to
      the altered cellular redox state due to increased superoxide anions and establish
      a new relationship between SOD1, LYS7, and the MEC1-mediated checkpoint response
      to replication arrest and DNA damage in S. cerevisiae.

PMID- 16287845
TI  - The neuroplasticity-associated arc gene is a direct transcriptional target of
      early growth response (Egr) transcription factors.
AB  - Early growth response (Egr) transcription factors (Egr1 to Egr4) are synaptic
      activity-inducible immediate early genes (IEGs) that regulate some aspects of
      synaptic plasticity-related to learning and memory, yet the target genes
      regulated by them are unknown. In particular, Egr1 is essential for persistence
      of late-phase long-term potentiation (L-LTP), for hippocampus-dependent long-term
      memory formation, and for reconsolidation of previously established memories.
      Here, we show that Egr1 and Egr3 directly regulate the plasticity-associated
      activity-regulated cytoskeletal-related (Arc) gene, a synaptic activity-induced
      effector molecule which is also required for L-LTP and hippocampus-dependent
      learning and memory processing. Moreover, Egr1-deficient and Egr3-deficient mice
      lack Arc protein in a subpopulation of neurons, while mice lacking both Egr1 and
      Egr3 lack Arc in all neurons. Thus, Egr1 and Egr3 can indirectly modulate
      synaptic plasticity by directly regulating Arc and the plasticity mechanisms it
      mediates in recently activated synapses.

PMID- 16287846
TI  - Histone-modifying complexes regulate gene expression pertinent to the
      differentiation of the protozoan parasite Toxoplasma gondii.
AB  - Pathogenic apicomplexan parasites like Toxoplasma and Plasmodium (malaria) have
      complex life cycles consisting of multiple stages. The ability to differentiate
      from one stage to another requires dramatic transcriptional changes, yet there is
      a paucity of transcription factors in these protozoa. In contrast, we show here
      that Toxoplasma possesses extensive chromatin remodeling machinery that modulates
      gene expression relevant to differentiation. We find that, as in other
      eukaryotes, histone acetylation and arginine methylation are marks of gene
      activation in Toxoplasma. We have identified mediators of these histone
      modifications, as well as a histone deacetylase (HDAC), and correlate their
      presence at target promoters in a stage-specific manner. We purified the first
      HDAC complex from apicomplexans, which contains novel components in addition to
      others previously reported in eukaryotes. A Toxoplasma orthologue of the arginine
      methyltransferase CARM1 appears to work in concert with the acetylase TgGCN5,
      which exhibits an unusual bias for H3 [K18] in vitro. Inhibition of TgCARM1
      induces differentiation, showing that the parasite life cycle can be manipulated
      by interfering with epigenetic machinery. This may lead to new approaches for
      therapy against protozoal diseases and highlights Toxoplasma as an informative
      model to study the evolution of epigenetics in eukaryotic cells.

PMID- 16287848
TI  - The reaper-binding protein scythe modulates apoptosis and proliferation during
      mammalian development.
AB  - Scythe (BAT3 [HLA-B-associated transcript 3]) is a nuclear protein that has been
      implicated in apoptosis, as it can modulate Reaper, a central apoptotic regulator
      in Drosophila melanogaster. While Scythe can markedly affect Reaper-dependent
      apoptosis in Xenopus laevis cell extracts, the function of Scythe in mammals is
      unknown. Here, we report that inactivation of Scythe in the mouse results in
      lethality associated with pronounced developmental defects in the lung, kidney,
      and brain. In all cases, these developmental defects were associated with
      dysregulation of apoptosis and cellular proliferation. Scythe-/- cells were also
      more resistant to apoptosis induced by menadione and thapsigargin. These data
      show that Scythe is critical for viability and normal development, probably via
      regulation of programmed cell death and cellular proliferation.

PMID- 16287847
TI  - The constitutive centromere component CENP-50 is required for recovery from
      spindle damage.
AB  - We identified CENP-50 as a novel kinetochore component. We found that CENP-50 is
      a constitutive component of the centromere that colocalizes with CENP-A and CENP
      H throughout the cell cycle in vertebrate cells. To determine the precise role of
      CENP-50, we examined its role in centromere function by generating a loss-of
      function mutant in the chicken DT40 cell line. The CENP-50 knockout was not
      lethal; however, the growth rate of cells with this mutation was slower than that
      of wild-type cells. We observed that the time for CENP-50-deficient cells to
      complete mitosis was longer than that for wild-type cells. Centromeric
      localization of CENP-50 was abolished in both CENP-H- and CENP-I-deficient cells.
      Coimmunoprecipitation experiments revealed that CENP-50 interacted with the CENP
      H/CENP-I complex in chicken DT40 cells. We also observed severe mitotic defects
      in CENP-50-deficient cells with apparent premature sister chromatid separation
      when the mitotic checkpoint was activated, indicating that CENP-50 is required
      for recovery from spindle damage.

PMID- 16287849
TI  - Gfi1 coordinates epigenetic repression of p21Cip/WAF1 by recruitment of histone
      lysine methyltransferase G9a and histone deacetylase 1.
AB  - The growth factor independent 1 (Gfi1) transcriptional regulator oncoprotein
      plays a crucial role in hematopoietic, inner ear, and pulmonary neuroendocrine
      cell development and governs cell processes as diverse as self-renewal of
      hematopoietic stem cells, proliferation, apoptosis, differentiation, cell fate
      specification, and oncogenesis. However, the molecular basis of its
      transcriptional functions has remained elusive. Here we show that Gfi1 recruits
      the histone lysine methyltransferase G9a and the histone deacetylase 1 (HDAC1) in
      order to modify the chromatin of genes targeted for repression by Gfi1. G9a and
      HDAC1 are both in a repressive complex assembled by Gfi1. Endogenous Gfi1
      colocalizes with G9a, HDAC1, and K9-dimethylated histone H3. Gfi1 associates with
      G9a and HDAC1 on the promoter of the cell cycle regulator p21Cip/WAF1, resulting
      in an increase in K9 dimethylation at histone H3. Silencing of Gfi1 expression in
      myeloid cells reverses G9a and HDAC1 recruitment to p21Cip/WAF1 and elevates its
      expression. These findings highlight the role of epigenetics in the regulation of
      development and oncogenesis by Gfi1.

PMID- 16287850
TI  - The putative NTPase Fap7 mediates cytoplasmic 20S pre-rRNA processing through a
      direct interaction with Rps14.
AB  - One of the proteins identified as being involved in ribosome biogenesis by high
      throughput studies, a putative P-loop-type kinase termed Fap7 (YDL166c), was
      shown to be required for the conversion of 20S pre-rRNA to 18S rRNA. However, the
      mechanism underlying this function has remained unclear. Here we demonstrate that
      Fap7 is strictly required for cleavage of the 20S pre-rRNA at site D in the
      cytoplasm. Genetic depletion of Fap7 causes accumulation of only the 20S pre
      rRNA, which could be detected not only in 43S preribosomes but also in 80S-sized
      complexes. Fap7 is not a structural component of 43S preribosomes but likely
      transiently interacts with them by directly binding to Rps14, a ribosomal protein
      that is found near the 3' end of the 18S rRNA. Consistent with an NTPase
      activity, conserved residues predicted to be required for nucleoside triphosphate
      (NTP) hydrolysis are essential for Fap7 function in vivo. We propose that Fap7
      mediates cleavage of the 20S pre-rRNA at site D by directly interacting with
      Rps14 and speculate that it is an enzyme that functions as an NTP-dependent
      molecular switch in 18S rRNA maturation.

PMID- 16287851
TI  - Sumoylation of p45/NF-E2: nuclear positioning and transcriptional activation of
      the mammalian beta-like globin gene locus.
AB  - NF-E2 is a transcription activator for the regulation of a number of erythroid-
      and megakaryocytic lineage-specific genes. Here we present evidence that the
      large subunit of mammalian NF-E2, p45, is sumoylated in vivo in human erythroid
      K562 cells and in mouse fetal liver. By in vitro sumoylation reaction and DNA
      transfection experiments, we show that the sumoylation occurs at lysine 368
      (K368) of human p45/NF-E2. Furthermore, p45 sumoylation enhances the
      transactivation capability of NF-E2, and this is accompanied by an increase of
      the NF-E2 DNA binding affinity. More interestingly, we have found that in K562
      cells, the beta-globin gene loci in the euchromatin regions are predominantly
      colocalized with the nuclear bodies promyelocytic leukemia protein (PML)
      oncogenic domains that are enriched with the PML, SUMO-1, RNA polymerase II, and
      sumoylatable p45/NF-E2. Chromatin immunoprecipitation assays further showed that
      the intact sumoylation site of p45/NF-E2 is required for its binding to the DNase
      I-hypersensitive sites of the beta-globin locus control region. Finally, we
      demonstrated by stable transfection assay that only the wild-type p45, but not
      its mutant form p45 (K368R), could efficiently rescue beta-globin gene expression
      in the p45-null, erythroid cell line CB3. These data together point to a model of
      mammalian beta-like globin gene activation by sumoylated p45/NF-E2 in erythroid
      cells.

PMID- 16287852
TI  - RBP-Jkappa/SHARP recruits CtIP/CtBP corepressors to silence Notch target genes.
AB  - Notch is a transmembrane receptor that determines cell fates and pattern
      formation in all animal species. After ligand binding, proteolytic cleavage steps
      occur and the intracellular part of Notch translocates to the nucleus, where it
      targets the DNA-binding protein RBP-Jkappa/CBF1. In the absence of Notch, RBP
      Jkappa represses Notch target genes through the recruitment of a corepressor
      complex. We and others have identified SHARP as a component of this complex.
      Here, we functionally demonstrate that the SHARP repression domain is necessary
      and sufficient to repress transcription and that the absence of this domain
      causes a dominant negative Notch-like phenotype. We identify the CtIP and CtBP
      corepressors as novel components of the human RBP-Jkappa/SHARP-corepressor
      complex and show that CtIP binds directly to the SHARP repression domain.
      Functionally, CtIP and CtBP augment SHARP-mediated repression. Transcriptional
      repression of the Notch target gene Hey1 is abolished in CtBP-deficient cells or
      after the functional knockout of CtBP. Furthermore, the endogenous Hey1 promoter
      is derepressed in CtBP-deficient cells. We propose that a corepressor complex
      containing CtIP/CtBP facilitates RBP-Jkappa/SHARP-mediated repression of Notch
      target genes.

PMID- 16287853
TI  - Exclusive ubiquitination and sumoylation on overlapping lysine residues mediate
      NF-kappaB activation by the human T-cell leukemia virus tax oncoprotein.
AB  - The transcription factor NF-kappaB is critical for the induction of cancer,
      including adult T-cell leukemia, which is linked to infection by human T-cell
      leukemia virus type 1 and the expression of its regulatory protein Tax. Although
      activation of the NF-kappaB pathway by Tax involves its interaction with the
      regulatory subunit of the IkappaB kinase (IKK) complex, NEMO/IKKgamma, the
      mechanism by which Tax activates specific cellular genes in the nucleus remains
      unknown. Here, we demonstrate that the attachment of SUMO-1 to Tax regulates its
      localization in nuclear bodies and the recruitment of both the RelA subunit of NF
      kappaB and free IKKgamma in these nuclear structures. However, this sumoylation
      step is not sufficient for the activation of the NF-kappaB pathway by Tax. This
      activity requires the prior ubiquitination and colocalization of ubiquitinated
      Tax with IKK complexes in the cytoplasm and the subsequent migration of the RelA
      subunit of NF-kappaB to the nucleus. Thus, the ubiquitination and sumoylation of
      Tax function in concert to result in the migration of RelA to the nucleus and its
      accumulation with IKKgamma in nuclear bodies for activation of gene expression.
      These modifications may result in targets for the treatment of adult T-cell
      leukemia.

PMID- 16287854
TI  - Dosage-dependent effects of Akt1/protein kinase Balpha (PKBalpha) and
      Akt3/PKBgamma on thymus, skin, and cardiovascular and nervous system development
      in mice.
AB  - Akt/protein kinase B (PKB) plays a critical role in the regulation of metabolism,
      transcription, cell migration, cell cycle progression, and cell survival. The
      existence of viable knockout mice for each of the three isoforms suggests
      functional redundancy. We generated mice with combined mutant alleles of Akt1 and
      Akt3 to study their effects on mouse development. Here we show that Akt1-/-
      Akt3+/- mice display multiple defects in the thymus, heart, and skin and die
      within several days after birth, while Akt1+/- Akt3-/- mice survive normally.
      Double knockout (Akt1-/-) Akt3-/-) causes embryonic lethality at around embryonic
      days 11 and 12, with more severe developmental defects in the cardiovascular and
      nervous systems. Increased apoptosis was found in the developing brain of double
      mutant embryos. These data indicate that the Akt1 gene is more essential than
      Akt3 for embryonic development and survival but that both are required for embryo
      development. Our results indicate isoform-specific and dosage-dependent effects
      of Akt on animal survival and development.

PMID- 16287855
TI  - Ytm1, Nop7, and Erb1 form a complex necessary for maturation of yeast 66S
      preribosomes.
AB  - The essential, conserved yeast nucleolar protein Ytm1 is one of 17 proteins in
      ribosome assembly intermediates that contain WD40 protein-protein interaction
      motifs. Such proteins may play key roles in organizing other molecules necessary
      for ribosome biogenesis. Ytm1 is present in four consecutive 66S preribosomes
      containing 27SA2, 27SA3, 27SB, and 25.5S plus 7S pre-rRNAs plus ribosome assembly
      factors and ribosomal proteins. Ytm1 binds directly to Erb1 and is present in a
      heterotrimeric subcomplex together with Erb1 and Nop7, both within preribosomes
      and independently of preribosomes. However, Nop7 and Erb1 assemble into
      preribosomes prior to Ytm1. Mutations in the WD40 motifs of Ytm1 disrupt binding
      to Erb1, destabilize the heterotrimer, and delay pre-rRNA processing and nuclear
      export of preribosomes. Nevertheless, 66S preribosomes lacking Ytm1 remain
      otherwise intact.

PMID- 16287856
TI  - Hairless-mediated repression of notch target genes requires the combined activity
      of Groucho and CtBP corepressors.
AB  - Notch signal transduction centers on a conserved DNA-binding protein called
      Suppressor of Hairless [Su(H)] in Drosophila species. In the absence of Notch
      activation, target genes are repressed by Su(H) acting in conjunction with a
      partner, Hairless, which contains binding motifs for two global corepressors,
      CtBP and Groucho (Gro). Usually these corepressors are thought to act via
      different mechanisms; complexed with other transcriptional regulators, they
      function independently and/or redundantly. Here we have investigated the
      requirement for Gro and CtBP in Hairless-mediated repression. Unexpectedly, we
      find that mutations inactivating one or the other binding motif can have
      detrimental effects on Hairless similar to those of mutations that inactivate
      both motifs. These results argue that recruitment of one or the other corepressor
      is not sufficient to confer repression in the context of the Hairless-Su(H)
      complex; Gro and CtBP need to function in combination. In addition, we
      demonstrate that Hairless has a second mode of repression that antagonizes Notch
      intracellular domain and is independent of Gro or CtBP binding.

PMID- 16287857
TI  - SF-1 (nuclear receptor 5A1) activity is activated by cyclic AMP via p300-mediated
      recruitment to active foci, acetylation, and increased DNA binding.
AB  - Steroidogenic factor 1 (SF-1) is a nuclear receptor essential for steroidogenic
      gene expression, but how its activity is regulated is unclear. Here we
      demonstrate that p300 plays an important role in regulating SF-1 function. SF-1
      was acetylated in vitro and in vivo by p300 at the KQQKK motif in the Ftz-F1
      (Fushi-tarazu factor 1) box adjacent to its DNA-binding domain. Mutation of the
      KQQKK motif reduced the DNA-binding activity and p300-dependent activation of SF
      1. When stimulated with cyclic AMP (cAMP), adrenocortical Y1 cells expressed more
      p300, leading to additional SF-1 association with p300 and increased SF-1
      acetylation and DNA binding. It also increased SF-1 colocalization with p300 in
      nuclear foci. Collectively, these results indicate that SF-1 transcriptional
      activity is regulated by p300 in response to the cAMP signaling pathway by way of
      increased acetylation, DNA binding, and recruitment to nuclear foci.

PMID- 16287859
TI  - Altered integration of matrilin-3 into cartilage extracellular matrix in the
      absence of collagen IX.
AB  - The matrilins are a family of four noncollagenous oligomeric extracellular matrix
      proteins with a modular structure. Matrilins can act as adapters which bridge
      different macromolecular networks. We therefore investigated the effect of
      collagen IX deficiency on matrilin-3 integration into cartilage tissues. Mice
      harboring a deleted Col9a1 gene lack synthesis of a functional protein and
      produce cartilage fibrils completely devoid of collagen IX. Newborn collagen IX
      knockout mice exhibited significantly decreased matrilin-3 and cartilage
      oligomeric matrix protein (COMP) signals, particularly in the cartilage
      primordium of vertebral bodies and ribs. In the absence of collagen IX, a
      substantial amount of matrilin-3 is released into the medium of cultured
      chondrocytes instead of being integrated into the cell layer as in wild-type and
      COMP-deficient cells. Gene expression of matrilin-3 is not affected in the
      absence of collagen IX, but protein extraction from cartilage is greatly
      facilitated. Matrilin-3 interacts with collagen IX-containing cartilage fibrils,
      while fibrils from collagen IX knockout mice lack matrilin-3, and COMP-deficient
      fibrils exhibit an intermediate integration. In summary, the integration of
      matrilin-3 into cartilage fibrils occurs both by a direct interaction with
      collagen IX and indirectly with COMP serving as an adapter. Matrilin-3 can be
      considered as an interface component, capable of interconnecting macromolecular
      networks and mediating interactions between cartilage fibrils and the
      extrafibrillar matrix.

PMID- 16287858
TI  - Generation and characterization of p38beta (MAPK11) gene-targeted mice.
AB  - p38 mitogen-activated protein kinases (MAPKs) are activated primarily in response
      to inflammatory cytokines and cellular stress, and inhibitors which target the
      p38alpha and p38beta MAPKs have shown potential for the treatment of inflammatory
      disease. Here we report the generation and initial characterization of a knockout
      of the p38beta (MAPK11) gene. p38beta-/- mice were viable and exhibited no
      apparent health problems. The expression and activation of p38alpha, ERK1/2, and
      JNK in response to cellular stress was normal in embryonic fibroblasts from
      p38beta-/- mice, as was the activation of p38-activated kinases MAPKAP-K2 and
      MSK1. The transcription of p38-dependent immediate-early genes was also not
      affected by the knockout of p38beta, suggesting that p38alpha is the predominant
      isoform involved in these processes. The p38beta-/- mice also showed normal T
      cell development. Lipopolysaccharide-induced cytokine production was also normal
      in the p38beta-/- mice. As p38 is activated by tumor necrosis factor, the p38beta
      /- mice were crossed onto a TNFDeltaARE mouse line. These mice overexpress tumor
      necrosis factor, which results in development symptoms similar to rheumatoid
      arthritis and inflammatory bowel disease. The progression of these diseases was
      not however moderated by knockout of p38beta. Together these results suggest that
      p38alpha, and not p38beta, is the major p38 isoform involved in the immune
      response and that it would not be necessary to retain activity against p38beta
      during the development of p38 inhibitors.

PMID- 16287860
TI  - Hypoxia-inducible factors 1alpha and 2alpha regulate trophoblast differentiation.
AB  - Placental development initially occurs in a low-oxygen (O2) or hypoxic
      environment. In this report we show that two hypoxia-inducible factors (HIFs),
      HIF1alpha and HIF2alpha, are essential for determining murine placental cell
      fates. HIF is a heterodimer composed of HIFalpha and HIFbeta (ARNT) subunits.
      Placentas from Arnt-/- and Hif1alpha-/- Hif2alpha-/- embryos exhibit defective
      placental vascularization and aberrant cell fate adoption. HIF regulation of
      Mash2 promotes spongiotrophoblast differentiation, a prerequisite for trophoblast
      giant cell differentiation. In the absence of Arnt or Hifalpha, trophoblast stem
      cells fail to generate these cell types and become labyrinthine trophoblasts
      instead. Therefore, HIF mediates placental morphogenesis, angiogenesis, and cell
      fate decisions, demonstrating that O2 tension is a critical regulator of
      trophoblast lineage determination. This novel genetic approach provides new
      insights into the role of O2 tension in the development of life-threatening
      pregnancy-related diseases such as preeclampsia.

PMID- 16287861
TI  - Werner protein protects nonproliferating cells from oxidative DNA damage.
AB  - Werner syndrome, caused by mutations of the WRN gene, mimics many changes of
      normal aging. Although roles for WRN protein in DNA replication, recombination,
      and telomere maintenance have been suggested, the pathology of rapidly dividing
      cells is not a feature of Werner syndrome. To identify cellular events that are
      specifically vulnerable to WRN deficiency, we used RNA interference (RNAi) to
      knockdown WRN or BLM (the RecQ helicase mutated in Bloom syndrome) expression in
      primary human fibroblasts. Withdrawal of WRN or BLM produced accelerated cellular
      senescence phenotype and DNA damage response in normal fibroblasts, as evidenced
      by induction of gammaH2AX and 53BP1 nuclear foci. After WRN depletion, the
      induction of these foci was seen most prominently in nondividing cells. Growth in
      physiological (3%) oxygen or in the presence of an antioxidant prevented the
      development of the DNA damage foci in WRN-depleted cells, whereas acute oxidative
      stress led to inefficient repair of the lesions. Furthermore, WRN RNAi-induced
      DNA damage was suppressed by overexpression of the telomere-binding protein TRF2.
      These conditions, however, did not prevent the DNA damage response in BLM-ablated
      cells, suggesting a distinct role for WRN in DNA homeostasis in vivo. Thus,
      manifestations of Werner syndrome may reflect an impaired ability of slowly
      dividing cells to limit oxidative DNA damage.

PMID- 16287862
TI  - H3 lysine 9 methylation is maintained on a transcribed inverted repeat by
      combined action of SUVH6 and SUVH4 methyltransferases.
AB  - Transcribed inverted repeats are potent triggers for RNA interference and RNA
      directed DNA methylation in plants through the production of double-stranded RNA
      (dsRNA). For example, a transcribed inverted repeat of endogenous genes in
      Arabidopsis thaliana, PAI1-PAI4, guides methylation of itself as well as two
      unlinked duplicated PAI genes, PAI2 and PAI3. In previous work, we found that
      mutations in the SUVH4/KYP histone H3 lysine 9 (H3 K9) methyltransferase cause a
      loss of DNA methylation on PAI2 and PAI3, but not on the inverted repeat. Here we
      use chromatin immunoprecipitation analysis to show that the transcribed inverted
      repeat carries H3 K9 methylation, which is maintained even in an suvh4 mutant.
      PAI1-PAI4 H3 K9 methylation and DNA methylation are also maintained in an suvh6
      mutant, which is defective for a gene closely related to SUVH4. However, both
      epigenetic modifications are reduced at this locus in an suvh4 suvh6 double
      mutant. In contrast, SUVH6 does not play a significant role in maintenance of H3
      K9 or DNA methylation on PAI2, transposon sequences, or centromere repeat
      sequences. Thus, SUVH6 is preferentially active at a dsRNA source locus versus
      targets for RNA-directed chromatin modifications.

PMID- 16287863
TI  - Anaphase-promoting complex/cyclosome controls the stability of TPX2 during
      mitotic exit.
AB  - TPX2, a microtubule-associated protein, is required downstream of Ran-GTP to
      induce spindle assembly. TPX2 activity appears to be tightly regulated during the
      cell cycle, and we report here one molecular mechanism for this regulation. We
      found that TPX2 protein levels are cell cycle regulated, peaking in mitosis and
      declining sharply during mitotic exit. TPX2 is degraded in mitotic extracts, as
      well as in HeLa cells exiting from mitosis. This instability depends, both in
      vitro and in vivo, on the anaphase-promoting complex/cyclosome (APC/C), a
      ubiquitin ligase that controls mitotic progression. In a reconstituted system,
      TPX2 is efficiently ubiquitinated by APC/C that has been activated by Cdh1. Two
      discrete elements in TPX2 are required for recognition by APC/C(Cdh1): a KEN box
      and a novel element in amino acids 1 to 86. Interestingly, the latter element,
      which has no known APC/C recognition motifs, is required for the ubiquitination
      of TPX2 by APC/C(Cdh1) in vitro and for its degradation in vivo. We conclude that
      APC/C(Cdh1) controls the stability of TPX2, thereby ensuring accurate regulation
      of the spindle assembly in the cell cycle.

PMID- 16287864
TI  - PSF1 is essential for early embryogenesis in mice.
AB  - Psf1 (partner of sld five 1) forms a novel heterotetramer complex, GINS (Go,
      Ichi, Nii, and San; five, one, two, and three, respectively, in Japanese), with
      Sld5, Psf2, and Psf3. The formation of this complex is essential for the
      initiation of DNA replication in yeast and Xenopus laevis egg extracts. Although
      all of the components are well conserved in higher eukaryotes, the biological
      function in vivo is largely unknown. We originally cloned the mouse ortholog of
      PSF1 from a hematopoietic stem cell cDNA library and found that PSF1 is expressed
      in blastocysts, adult bone marrow, and testis, in which the stem cell system is
      active. Here we used the gene-targeting technique to determine the physiological
      function of PSF1 in vivo. Mice homozygous for a nonfunctional mutant of PSF1 died
      in utero around the time of implantation. PSF1-/- blastocysts failed to show
      outgrowth in culture and exhibited a cell proliferation defect. Our data clearly
      indicate that PSF1 is required for early embryogenesis.

PMID- 16287865
TI  - The ubiquitously expressed Csk adaptor protein Cbp is dispensable for
      embryogenesis and T-cell development and function.
AB  - Regulation of Src family kinase (SFK) activity is indispensable for a functional
      immune system and embryogenesis. The activity of SFKs is inhibited by the
      presence of the carboxy-terminal Src kinase (Csk) at the cell membrane. Thus,
      recruitment of cytosolic Csk to the membrane-associated SFKs is crucial for its
      regulatory function. Previous studies utilizing in vitro and transgenic models
      suggested that the Csk-binding protein (Cbp), also known as phosphoprotein
      associated with glycosphingolipid microdomains (PAG), is the membrane adaptor for
      Csk. However, loss-of-function genetic evidence to support this notion was
      lacking. Herein, we demonstrate that the targeted disruption of the cbp gene in
      mice has no effect on embryogenesis, thymic development, or T-cell functions in
      vivo. Moreover, recruitment of Csk to the specialized membrane compartment of
      "lipid rafts" is not impaired by Cbp deficiency. Our results indicate that Cbp is
      dispensable for the recruitment of Csk to the membrane and that another Csk
      adaptor, yet to be discovered, compensates for the loss of Cbp.

PMID- 16287866
TI  - Regulation of caspase 9 through phosphorylation by protein kinase C zeta in
      response to hyperosmotic stress.
AB  - Caspase 9 is a critical component of the mitochondrial or intrinsic apoptotic
      pathway and is activated by Apaf-1 following release of cytochrome c from
      mitochondria in response to a variety of stimuli. Caspase 9 cleaves and activates
      effector caspases, mainly caspase 3, leading to the demise of the cell. Survival
      signaling pathways can impinge on this pathway to restrain apoptosis. Here, we
      have identified Ser144 of human caspase 9as an inhibitory site that is
      phosphorylated in a cell-free system and in cells in response to the protein
      phosphatase inhibitor okadaic acid. Inhibitor sensitivity and interactions with
      caspase 9 indicate that the predominant kinase that targets Ser144 is the
      atypical protein kinase C isoform zeta (PKCzeta). Prevention of Ser144
      phosphorylation by inhibition of PKCzeta or mutation of caspase 9 promotes
      caspase 3 activation. Phosphorylation of serine 144 in cells is also induced by
      hyperosmotic stress, which activates PKCzeta and regulates its interaction with
      caspase 9, but not by growth factors, phorbol ester, or other cellular stresses.
      These results indicate that phosphorylation and inhibition of caspase 9 by
      PKCzeta restrain the intrinsic apoptotic pathway during hyperosmotic stress. This
      work provides further evidence that caspase 9 acts as a focal point for multiple
      protein kinase signaling pathways that regulate apoptosis.

PMID- 16287867
TI  - Eukaryotic translation initiation factor 4E availability controls the switch
      between cap-dependent and internal ribosomal entry site-mediated translation.
AB  - Translation of m7G-capped cellular mRNAs is initiated by recruitment of ribosomes
      to the 5' end of mRNAs via eukaryotic translation initiation factor 4F (eIF4F), a
      heterotrimeric complex comprised of a cap-binding subunit (eIF4E) and an RNA
      helicase (eIF4A) bridged by a scaffolding molecule (eIF4G). Internal translation
      initiation bypasses the requirement for the cap and eIF4E and occurs on viral and
      cellular mRNAs containing internal ribosomal entry sites (IRESs). Here we
      demonstrate that eIF4E availability plays a critical role in the switch from cap
      dependent to IRES-mediated translation in picornavirus-infected cells. When both
      capped and IRES-containing mRNAs are present (as in intact cells or in vitro
      translation extracts), a decrease in the amount of eIF4E associated with the
      eIF4F complex elicits a striking increase in IRES-mediated viral mRNA
      translation. This effect is not observed in translation extracts depleted of
      capped mRNAs, indicating that capped mRNAs compete with IRES-containing mRNAs for
      translation. These data explain numerous reported observations where viral mRNAs
      are preferentially translated during infection.

PMID- 16287869
TI  - Multisite M-phase phosphorylation of Xenopus Wee1A.
AB  - The Cdk1 inhibitor Wee1 is inactivated during mitotic entry by proteolysis,
      translational regulation, and transcriptional regulation. Wee1 is also regulated
      by posttranslational modifications, and here we have identified five
      phosphorylation sites in the N-terminal domain of embryonic Xenopus Wee1A through
      a combination of mutagenesis studies and matrix-assisted laser desorption
      ionization-time of flight mass spectrometry. All five sites conform to the Ser
      Pro/Thr-Pro consensus for proline-directed kinases like Cdks. Three of the sites
      (Ser 38, Thr 53, and Ser 62) are required for the mitotic gel shift, and at least
      two of these sites (Ser 38 and Thr 53) regulate the proteolysis of Wee1A during
      interphase. The other two sites (Thr 104 and Thr 150) are primarily responsible
      for the mitotic inactivation of Wee1A. Alanine mutants of Thr 150 or Thr 104 had
      an increased capacity to inhibit mitotic entry in cyclin B-treated interphase
      extracts, and Thr 150 was found to be transiently phosphorylated just prior to
      nuclear envelope breakdown in cycling egg extracts. These findings establish the
      phosphorylation-dependent direct inactivation of Wee1A as a critical mechanism
      for the promotion of M-phase entry. These results also show that multisite
      phosphorylation cooperatively inactivates Wee1A and cooperatively promotes Wee1A
      proteolysis.

PMID- 16287868
TI  - Histone H3 Ser10 phosphorylation-independent function of Snf1 and Reg1 proteins
      rescues a gcn5- mutant in HIS3 expression.
AB  - Gcn5 protein is a prototypical histone acetyltransferase that controls
      transcription of multiple yeast genes. To identify molecular functions that act
      downstream of or in parallel with Gcn5 protein, we screened for suppressors that
      rescue the transcriptional defects of HIS3 caused by a catalytically inactive
      mutant Gcn5, the E173H mutant. One bypass of Gcn5 requirement gene (BGR)
      suppressor was mapped to the REG1 locus that encodes a semidominant mutant
      truncated after amino acid 740. Reg1(1-740) protein does not rescue the complete
      knockout of GCN5, nor does it suppress other gcn5- defects, including the
      inability to utilize nonglucose carbon sources. Reg1(1-740) enhances HIS3
      transcription while HIS3 promoter remains hypoacetylated, indicating that a
      noncatalytic function of Gcn5 is targeted by this suppressor protein. Reg1
      protein is a major regulator of Snf1 kinase that phosphorylates Ser10 of histone
      H3. However, whereas Snf1 protein is important for HIS3 expression, replacing
      Ser10 of H3 with alanine or glutamate neither attenuates nor augments the BGR
      phenotypes. Overproduction of Snf1 protein also preferentially rescues the E173H
      allele. Biochemically, both Snf1 and Reg1(1-740) proteins copurify with Gcn5
      protein. Snf1 can phosphorylate recombinant Gcn5 in vitro. Together, these data
      suggest that Reg1 and Snf1 proteins function in an H3 phosphorylation-independent
      pathway that also involves a noncatalytic role played by Gcn5 protein.

PMID- 16287870
TI  - Impaired retinoic acid (RA) signal leads to RARbeta2 epigenetic silencing and RA
      resistance.
AB  - Resistance to the growth-inhibitory action of retinoic acid (RA), the bioactive
      derivative of vitamin A, is common in human tumors. One form of RA resistance has
      been associated with silencing and hypermethylation of the retinoic acid receptor
      beta2 gene (RARbeta2), an RA-regulated tumor suppressor gene. The presence of an
      epigenetically silent RARbeta2 correlates with lack of the RA receptor alpha
      (RARalpha). Normally, RARalpha regulates RARbeta2 transcription by mediating
      dynamic changes of RARbeta2 chromatin in the presence and absence of RA. Here we
      show that interfering with RA signal through RARalpha (which was achieved by use
      of a dominant-negative RARalpha, by downregulation of RARalpha by RNA
      interference, and by use of RARalpha antagonists) induces an exacerbation of the
      repressed chromatin status of RARbeta2 and leads to RARbeta2 transcriptional
      silencing. Further, we demonstrate that RARbeta2 silencing causes resistance to
      the growth-inhibitory effect of RA. Apparently, RARbeta2 silencing can also occur
      in the absence of DNA methylation. Conversely, we demonstrate that restoration of
      RA signal at a silent RARbeta2 through RARalpha leads to RARbeta2 reactivation.
      This report provides proof of principle that RARbeta2 silencing and RA resistance
      are consequent to an impaired integration of RA signal at RARbeta2 chromatin.

PMID- 16287871
TI  - The murine stanniocalcin 1 gene is not essential for growth and development.
AB  - The stanniocalcin 1 (STC1) gene is expressed in a wide variety of tissues,
      including the kidney, prostate, thyroid, bone, and ovary. STC1 protein is
      considered to have roles in many physiological processes, including bone
      development, reproduction, wound healing, angiogenesis, and modulation of
      inflammatory response. In fish, STC1 is a hormone that is secreted by the
      corpuscles of Stannius and is involved in calcium and phosphate homeostasis. To
      determine the role of STC1 in mammals, we generated Stc1-null mice by gene
      targeting. The number of Stc1-/- mice obtained was in accordance with Mendelian
      ratios, and both males and females produced offspring normally. No anatomical or
      histological abnormalities were detected in any tissues. Our results demonstrated
      that Stc1 function is not essential for growth or reproduction in the mouse.

PMID- 16287873
TI  - REM1, a new type of long terminal repeat retrotransposon in Chlamydomonas
      reinhardtii.
AB  - A new long terminal repeat (LTR) retrotransposon, named REM1, has been identified
      in the green alga Chlamydomonas reinhardtii. It was found in low copy number,
      highly methylated, and with an inducible transpositional activity. This
      retrotransposon is phylogenetically related to Ty3-gypsy LTR retrotransposons and
      possesses new and unusual structural features. A regulatory module, ORF3p, is
      present in an inverse transcriptional orientation to that of the polyprotein and
      contains PHD-finger and chromodomains, which might confer specificity of the
      target site and are highly conserved in proteins involved in transcriptional
      regulation by chromatin remodeling. By using different wild-type and mutant
      strains, we show that CrREM1 was active with a strong transcriptional activity
      and amplified its copy number in strains that underwent foreign DNA integration
      and/or genetic crosses. However, integration of CrREM1 was restricted to these
      events even though the expression of its full-length transcripts remained highly
      activated. A regulatory mechanism of CrREM1 retrotransposition which would help
      to minimize its deleterious effects in the host genome is proposed.

PMID- 16287872
TI  - The Sho1 adaptor protein links oxidative stress to morphogenesis and cell wall
      biosynthesis in the fungal pathogen Candida albicans.
AB  - The Sho1 adaptor protein is an important element of one of the two upstream
      branches of the high-osmolarity glycerol (HOG) mitogen-activated protein (MAP)
      kinase pathway in Saccharomyces cerevisiae, a signal transduction cascade
      involved in adaptation to stress. In the present work, we describe its role in
      the pathogenic yeast Candida albicans by the construction of mutants altered in
      this gene. We report here that sho1 mutants are sensitive to oxidative stress but
      that Sho1 has a minor role in the transmission of the phosphorylation signal to
      the Hog1 MAP kinase in response to oxidative stress, which mainly occurs through
      a putative Sln1-Ssk1 branch of the HOG pathway. Genetic analysis revealed that
      double ssk1 sho1 mutants were still able to grow on high-osmolarity media and
      activate Hog1 in response to this stress, indicating the existence of alternative
      inputs of the pathway. We also demonstrate that the Cek1 MAP kinase is
      constitutively active in hog1 and ssk1 mutants, a phenotypic trait that
      correlates with their resistance to the cell wall inhibitor Congo red, and that
      Sho1 is essential for the activation of the Cek1 MAP kinase under different
      conditions that require active cell growth and/or cell wall remodeling, such as
      the resumption of growth upon exit from the stationary phase. sho1 mutants are
      also sensitive to certain cell wall interfering compounds (Congo red, calcofluor
      white), presenting an altered cell wall structure (as shown by the ability to
      aggregate), and are defective in morphogenesis on different media, such as SLAD
      and Spider, that stimulate hyphal growth. These results reveal a role for the
      Sho1 protein in linking oxidative stress, cell wall biogenesis, and morphogenesis
      in this important human fungal pathogen.

PMID- 16287874
TI  - Assembly and disassembly of nucleosome core particles containing histone variants
      by human nucleosome assembly protein I.
AB  - Histone variants play important roles in the maintenance and regulation of the
      chromatin structure. In order to characterize the biochemical properties of the
      chromatin structure containing histone variants, we investigated the dynamic
      status of nucleosome core particles (NCPs) that were assembled with recombinant
      histones. We found that in the presence of nucleosome assembly protein I (NAP-I),
      a histone chaperone, H2A-Barr body deficient (H2A.Bbd) confers the most flexible
      nucleosome structure among the mammalian histone H2A variants known thus far. NAP
      I mediated the efficient assembly and disassembly of the H2A.Bbd-H2B dimers from
      NCPs. This reaction was accomplished more efficiently when the NCPs contained
      H3.3, a histone H3 variant known to be localized in the active chromatin, than
      when the NCPs contained the canonical H3. These observations indicate that the
      histone variants H2A.Bbd and H3.3 are involved in the formation and maintenance
      of the active chromatin structure. We also observed that acidic histone binding
      proteins, TAF-I/SET and B23.1, demonstrated dimer assembly and disassembly
      activity, but the efficiency of their activity was considerably lower than that
      of NAP-I. Thus, both the acidic nature of NAP-I and its other functional
      structure(s) may be essential to mediate the assembly and disassembly of the
      dimers in NCPs.

PMID- 16287877
TI  - Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity,
      alcohol consumption and breast cancer risk in a prospective cohort study.
AB  - Breast cancer may be related to oxidative stress. Breast cancer patients have
      been reported to have lower antioxidant enzyme activity than healthy controls and
      the polymorphism GPX1 Pro198Leu has been associated with risk of lung and breast
      cancer. The purpose of the present nested case-control study was to determine
      whether GPX1 Pro198Leu and glutathione peroxidase (GPX) activity in prospectively
      collected blood samples are associated with breast cancer risk among
      postmenopausal women and whether GPX activity levels are associated with other
      known breast cancer risk factors. We matched 377 female breast cancer cases with
      377 controls all nested within the prospective 'Diet, Cancer and Health' study of
      57 000 Danes. Carriers of the variant T-allele of GPX1 Pro198Leu were at 1.43
      fold higher risk of breast cancer compared with non-carriers (95% CI=1.07-1.92).
      Pre-diagnostic GPX activity tended to be lower in cases compared with controls.
      GPX activity was positively correlated with intake of alcohol (P<0.0001) and the
      catalytic activity was lowered 5% for each additional copy of the variant T
      allele (P=0.0003). Alcohol intake was correlated with increased GPX activity for
      the C-allele but not for the T-allele. Results from this prospective study
      suggest that the GPX1 Pro198Leu-associated lowered GPX activity is associated
      with higher breast cancer risk among Danish women.

PMID- 16287876
TI  - Autorepression of rfx1 gene expression: functional conservation from yeast to
      humans in response to DNA replication arrest.
AB  - The yeast Saccharomyces cerevisiae Crt1 transcription repressor is an effector of
      the DNA damage and replication checkpoint pathway. Crt1 binds and represses genes
      encoding ribonucleotide reductase (RNR) and its own promoter, establishing a
      negative-feedback pathway. The role of Rfx1, the mammalian Crt1 homologue,
      remained uncertain. In this study we investigated the possibility that Rfx1 plays
      a similar function in animal cells. We show here that, like Crt1, Rfx1 binds and
      represses its own promoter. Furthermore, Rfx1 binding to its promoter is reduced
      upon induction of a DNA replication block by hydroxyurea, which led to a release
      of repression. Significantly, like Crt1, Rfx1 binds and represses the RNR-R2
      gene. Upon blocking replication and UV treatment, expression of both Rfx1 and RNR
      R2 is induced; however, unlike the results seen with the RNR-R2 gene, the
      derepression of the RFX1 gene is only partially blocked by inhibiting Chk1, the
      DNA checkpoint kinase. This report provides evidence for a common mechanism for
      Crt1 and Rfx1 expression and for the conservation of their mode of action in
      response to a DNA replication block. We suggest that Rfx1 plays a role in the DNA
      damage response by down-regulating a subset of genes whose expression is
      increased in response to replication blocking and UV-induced DNA damage.

PMID- 16287875
TI  - Inactivation of Ku-mediated end joining suppresses mec1Delta lethality by
      depleting the ribonucleotide reductase inhibitor Sml1 through a pathway
      controlled by Tel1 kinase and the Mre11 complex.
AB  - RAD53 and MEC1 are essential Saccharomyces cerevisiae genes required for the DNA
      replication and DNA damage checkpoint responses. Their lethality can be
      suppressed by increasing the intracellular pool of deoxynucleotide triphosphates.
      We report that deletion of YKU70 or YKU80 suppresses mec1Delta, but not
      rad53Delta, lethality. We show that suppression of mec1Delta lethality is not due
      to Ku--associated telomeric defects but rather results from the inability of Ku-
      cells to efficiently repair DNA double strand breaks by nonhomologous end
      joining. Consistent with these results, mec1Delta lethality is also suppressed by
      lif1Delta, which like yku70Delta and yku80Delta, prevents nonhomologous end
      joining. The viability of yku70Delta mec1Delta and yku80Delta mec1Delta cells
      depends on the ATM-related Tel1 kinase, the Mre11-Rad50-Xrs2 complex, and the DNA
      damage checkpoint protein Rad9. We further report that this Mec1-independent
      pathway converges with the Rad53/Dun1-regulated checkpoint kinase cascade and
      leads to the degradation of the ribonucleotide reductase inhibitor Sml1.

PMID- 16287878
TI  - Experimental models of human bladder carcinogenesis.
AB  - Bladder cancer is the fifth most common cancer in the UK, yet human bladder
      carcinogenesis remains poorly understood and the response of bladder tumours to
      radio- and chemo-therapy is unpredictable. The aims of this article are to review
      human bladder carcinogenesis and appraise the different in vitro and in vivo
      approaches that have been developed to study the process. The review considers
      how in vitro models based on normal human urothelial (NHU) cells can be applied
      to human bladder cancer research. We conclude that recent advances in NHU cell
      culture offer novel approaches for defining urothelial tissue-specific responses
      to genotoxic and non-genotoxic carcinogens and elucidating the role of specific
      genes involved in the mechanisms of bladder carcinogenesis and malignant
      progression.

PMID- 16287879
TI  - Introduction.

PMID- 16287880
TI  - Building a research consortium of large health systems: the Cancer Research
      Network.
AB  - Critical questions about cancer prevention, care, and outcomes increasingly
      require research involving large patient populations and their care delivery
      organizations. The Cancer Research Network (CRN) includes 11 integrated health
      systems funded by the National Cancer Institute (NCI) to conduct collaborative
      cancer research. This article describes the challenges of constructing a
      productive consortium of large health systems, and explores the CRN's responses.
      The CRN was initially funded through an NCI cooperative agreement in 1999 and has
      since received a second 4-year grant. Leadership and policy development are
      provided through a steering committee, subcommittees, and an external advisory
      committee. The CRN includes integral and affiliated research projects supported
      by a Scientific and Data Resources Core. Three characteristics of the CRN
      intensified the general challenges of consortium research: 1) its members are
      large health systems with legitimate concerns about confidentiality of data about
      enrollees, providers, and the organization; 2) CRN research projects often
      generate highly sensitive data about quality of care; and therefore 3) each
      participating organization wants a strong voice in CRN direction. CRN experience
      to date confirms that a consortium of health systems with internal research
      capacity can address a range of important cancer research questions that would be
      difficult to study in other venues. The advantages and challenges of consortium
      research are explored, with suggestions for the development, execution, and
      management of multisystem population laboratories.

PMID- 16287881
TI  - Building a virtual cancer research organization.
AB  - BACKGROUND: The Cancer Research Network (CRN) comprises the National Cancer
      Institute and 11 nonprofit research centers affiliated with integrated health
      care delivery systems. The CRN, a public/private partnership, fosters multisite
      collaborative research on cancer prevention, screening, treatment, survival, and
      palliation in diverse populations. METHODS: The CRN's success hinges on producing
      innovative cancer research that likely would not have been developed by
      scientists working individually, and then translating those findings into
      clinical practice within multiple population laboratories. The CRN is a
      collaborative virtual research organization characterized by user-defined sharing
      among scientists and health care providers of data files as well as direct access
      to researchers, computers, software, data, research participants, and other
      resources. The CRN's research management Web site fosters a high-functioning
      virtual scientific community by publishing standardized data definitions, file
      specifications, and computer programs to support merging and analyzing data from
      multiple health care systems. RESULTS: Seven major types of standardized data
      files developed to date include demographics, health plan eligibility, tumor
      registry, inpatient and ambulatory utilization, medication dispensing, laboratory
      tests, and imaging procedures; more will follow. Data standardization avoids
      rework, increases multisite data integrity, increases data security, generates
      shorter times from initial proposal concept to submission, and stimulates more
      frequent collaborations among scientists across multiple institutions.
      CONCLUSIONS: The CRN research management Web site and associated standardized
      data files and procedures represent a quasi-public resource, and the CRN stands
      ready to collaborate with researchers from outside institutions in developing and
      conducting innovative public domain research.

PMID- 16287882
TI  - Measuring and improving performance in multicenter research consortia.
AB  - BACKGROUND: Some evidence suggests that the quality of the organization and
      management of research consortia influences productivity and staff satisfaction.
      Collaborators in a research consortium generally focus on developing and
      implementing studies and thus rarely assess the process of collaboration. We
      present an approach to evaluating and improving a research consortium, using the
      HMO Cancer Research Network (CRN) as an example. METHODS: Five domains are
      evaluated: extent of collaboration and quality of communication; performance of
      projects and infrastructure; data quality; scientific productivity; and impact on
      member organizations. The primary assessment tool is a survey of CRN scientists
      and project staff, undertaken annually. RESULTS: Each year, the evaluation has
      identified critical aspects of this collaboration that could be improved. Several
      tangible changes have been implemented to improve productivity of the consortium.
      The most important result of the CRN Evaluation is the ability to have open
      dialogue about ways to improve its overall performance. CONCLUSION: Optimizing
      the process of collaboration will contribute to achievement of the scientific
      goals. The experience of the CRN provides a useful framework and process for
      evaluating the structure of consortium-based research.

PMID- 16287883
TI  - Characteristics of women refusing follow-up for tests or symptoms suggestive of
      breast cancer.
AB  - BACKGROUND: Delay in diagnosis of breast cancer can occur at several points on
      the diagnostic pathway. We examined characteristics of women with breast cancer
      who before diagnosis actively refused recommended follow-up of tests or symptoms
      suggestive of breast cancer. METHODS: We identified women aged 50 years or older
      diagnosed with late-stage (metastatic disease or tumors > or = 3 cm at diagnosis)
      and a matched sample of women with early-stage (tumors < 3 cm) breast cancer from
      1995 to 1999. Using medical records, we investigated clinical characteristics,
      use of health care, and documentation of care refusal during the 3 years before
      diagnosis. We used logistic regression models to compare refusers to nonrefusers.
      RESULTS: Of the 2694 women studied, 7.2% refused provider follow-up advice during
      the 3 years. These women were more likely to have late-stage breast cancer at
      diagnosis than were nonrefusers (odds ratio [OR] = 1.9, 95% confidence interval
      [CI] = 1.4 to 2.6). They were more likely to be aged 75 years or older (OR = 1.9,
      95% CI = 1.4 to 2.7 compared with age 50-64) or to have six or more children (OR
      = 2.3, 95% CI = 1.3 to 4.2 compared to women with one to two children). Clinical
      factors associated with refusal included low use of mammography, high use of
      clinical breast exam, and missed appointments. A minority of women who refused
      had a reason documented in the medical record; the most frequent reasons were
      avoidance-denial-fatalism, fear of diagnostic tests, and fear of surgery or
      disfigurement. CONCLUSIONS: Our results suggest that certain demographic and
      clinical characteristics are associated with women's refusal of diagnostic
      testing for breast cancer. Further study is needed on refusers' characteristics
      and on how such refusals affect outcomes. Efforts aimed at identifying and
      counseling women with abnormal results who refuse follow-up are warranted.

PMID- 16287884
TI  - Late-stage breast cancer among women with recent negative screening mammography:
      do clinical encounters offer opportunity for earlier detection?
AB  - BACKGROUND: Opportunities to prevent late-stage breast cancer within the course
      of usual care are needed. We evaluate whether clinical encounters offer such
      opportunities. METHODS: Within seven health care plans, we identified 1298 women
      aged more than 50 years with early (<3 cm), late-stage (> or = 3 cm), or
      metastatic invasive breast cancer diagnosed during 1995-1999, whose first
      screening mammogram 13-36 months prior to the diagnosis (index) was negative. We
      audited all care occurring in the health plans up to 36 months prior to the
      cancer diagnoses. Ordinal logistic regression compared the frequency of events by
      disease category. We hypothesized that during the 13-36 months prior to
      diagnosis, women with late-stage or metastatic breast cancer would have more
      symptoms and be more likely to have breast-related clinical visits but have less
      breast screening (clinical breast examination [CBE] or mammography) than women
      with early-stage disease, thereby indicating clinical opportunities for earlier
      detection. RESULTS: We found no differences in demographic characteristics across
      breast cancer stage among the 1298 women. Both before and after the negative
      index mammogram but during the 13-36 months prior to diagnosis, few women had
      breast symptoms (5% before index, 8% after), but many sought breast care (86%
      before index, 90% after) and screening CBE (62% before index, 43% after). Only
      the occurrence of screening CBE (odds ratio [OR] = 0.73, 95% confidence interval
      [CI] = 0.56 to 0.95) or screening mammograms (OR = 0.74, 95% CI = 0.57 to 0.97)
      after the negative index mammogram reduced odds of more severe disease at
      diagnosis. CONCLUSION: Although the mortality benefit of CBE, or one compared to
      two year mammography has not been established, we found that women with late
      stage breast cancers undetected by screening mammography did not experience
      opportunities for earlier detection except through CBE or additional screening
      mammography.

PMID- 16287886
TI  - Women's decision-making roles regarding contralateral prophylactic mastectomy.
AB  - BACKGROUND: Contralateral prophylactic mastectomy (CPM) is the removal of a
      nonaffected breast in a woman with unilateral breast cancer and is effective in
      reducing the risk of recurrences. Little is known about women's decision-making
      roles regarding CPM. METHODS: Women aged 18-80 years with CPM performed at one of
      six health maintenance organizations between 1979 and 1999 were surveyed. We
      determined women's reported decision-making roles at the time of CPM, analyzed
      their trends over time, and explored the association between decision-making
      roles and psychosocial outcomes following CPM. RESULTS: We received 562 responses
      (response rate = 73%); 431 completed items needed for this analysis. Most
      respondents were white, younger than 55 years at CPM, married, and had CPM within
      10 years of completing the survey. Forty-five percent made the decision to
      undergo CPM alone, 37% considered their doctor's opinion, 15% shared the decision
      with their doctor and only 3% reported their doctor primarily made the decision.
      Women reporting active roles were more likely to be younger (P<.0008), college
      educated (P<.0001) and have CPM more recently (P = .002). Compared with those
      sharing the decision with their doctors, women with active roles were twice as
      likely to be satisfied 6 months following CPM (odds ratio [OR] = 2.2, 95%
      confidence interval [CI] = 1.1 to 4.2) and report current concern about breast
      cancer (OR = 1.9, 95% CI = 1.0 to 3.4). CONCLUSIONS: Most women reported active
      or shared roles in decision making regarding CPM, particularly younger women,
      those with college education, and those with recent CPM. Women with active roles
      were more often satisfied in the short term but were also more likely to report
      current concern about breast cancer. Whether higher concern is related to
      insufficient input from clinicians should be explored. Prospective data are
      needed.

PMID- 16287885
TI  - Breast and cervical cancer screening: clinicians' views on health plan guidelines
      and implementation efforts.
AB  - BACKGROUND: Optimizing breast and cervical cancer screening rates within health
      plans requires clinician support for screening guidelines, an awareness of
      whether there are tools available and functioning to aid screening
      implementation, and a perception of collegial and leadership support for quality
      screening services. This study investigated clinicians' perceptions of
      guidelines, reminders for screening, and plan and practice commitment in order to
      assess where opportunities exist to improve the screening process. METHODS: A
      stratified sample of 761 primary care clinicians from three comprehensive health
      plans were surveyed to assess awareness of and agreement with guideline elements,
      perception of guidelines' usefulness, awareness of plan strategies to promote
      guideline adherence, perception of support for high-quality screening services,
      and ratings of plan efforts to maximize members' access. RESULTS: Clinician
      awareness of and agreement with guideline elements was high (98% breast, 94%
      cervical). Across guideline elements, agreement was lower for mammography than
      cervical screening, notably for upper age limit recommendations (58% breast, 79%
      cervical). Knowledge of systems that cue patients and clinicians that screening
      is due varied by cancer test, and clinician report and plan report data about the
      existence of systems were, at times, not congruent. Views about consistent
      operation of systems differed by test (mammograms, 74%-92%; Pap, 66%-84%).
      Clinicians rated local colleagues and local and plan medical leadership as very
      committed to high-quality screening, albeit with somewhat lower ratings for
      cervical testing. Although the majority rated overall plan efforts to maximize
      screening as very good or excellent, perceived consistency of systems to cue a
      woman that she is due for testing and perception of collegial support were
      independently and significantly related to ratings of plan efforts. CONCLUSIONS:
      Improvements in knowledge of systems that support guideline implementation
      varied, and action to ensure accurate perception of reminders, as well as
      consistent implementation of systems, may be important for improving screening
      rates and outcomes. Plan efforts and clinician efforts at the practice level are
      closely linked and need to be aligned to maximize screening rates. This requires
      plan and practice-level analyses of structures and processes that could be
      improved.

PMID- 16287887
TI  - Complications following bilateral prophylactic mastectomy.
AB  - BACKGROUND: Bilateral prophylactic mastectomy significantly decreases breast
      cancer risk, but complications of the procedure have only been described in
      single-site studies. We describe the frequency and type of complications in women
      who underwent bilateral prophylactic mastectomy in a multisite community-based
      cohort. METHODS: Women aged 18-80 years undergoing bilateral prophylactic
      mastectomy without a personal history of breast cancer at one of six health plans
      were eligible. We identified women from automated data sources, then reviewed
      hospital data, ambulatory notes, and other chart elements to confirm eligibility
      and obtain all charted information about complications and surgeries performed
      after prophylactic mastectomy, including reconstructive procedures.
      Reconstructions were characterized by type (implant vs. tissue graft).
      Complications were noted for a 1-year period after any surgical procedure.
      RESULTS: We identified 269 women with prophylactic mastectomy who were followed
      for a mean of 7.4 years. Their mean age was 44.9 years. Nearly 80% undertook
      reconstruction, most with prosthetic implants. One or more complications occurred
      in 64%. The most common complications were pain (35% of women), infection (17%),
      and seroma (17%). Women with no reconstruction had fewer complications (mean of
      .93) than women who had implant (2.0) or tissue graft (2.4) reconstruction
      procedures (differences from no reconstruction: 1.07 [95% confidence interval =
      0.36 to 1.77] and 1.50 [95% confidence interval = 0.44 to 2.56] respectively).
      Delay of reconstruction after mastectomy was associated with a borderline
      significant higher risk of complications (80.6%) compared to simultaneous
      reconstruction (64.0%, P = .055). CONCLUSION: We found that almost two-thirds of
      women undergoing bilateral prophylactic mastectomy had at least one complication
      following surgery. Further work should be done to minimize and to understand the
      effect of complications of bilateral prophylactic mastectomy.

PMID- 16287888
TI  - Screening clinical breast examination: how often does it miss lethal breast
      cancer?
AB  - BACKGROUND: Although most American women regularly receive screening clinical
      breast examination (CBE), little is known about CBE accuracy in community
      practice. We sought to estimate the rate of cancer detection (sensitivity) of
      screening CBE performed by community-based clinicians on women who ultimately
      died of breast cancer, as well as to identify factors associated with accurate
      detection. SUBJECTS AND METHODS: We evaluated CBE accuracy among asymptomatic
      female health plan enrollees in five states (WA, OR, CA, MA, and MN) who received
      a CBE within 1 year of breast cancer diagnosis and who died of breast cancer
      within 15 years of diagnosis (N = 485). Sensitivity was estimated as the
      proportion whose exam was abnormal. Bivariate and logistic regression analyses
      identified patient characteristics associated with cancer detection. RESULTS: An
      abnormality was noted on screening CBE in one of five women who ultimately
      succumbed to breast cancer (sensitivity = 21.6%; 95% confidence interval [CI] =
      18.1% to 25.6%). The odds of a true-positive screening CBE (sensitivity) were
      decreased among women using estrogen (odds ratio [OR] = 0.23; 95% CI = 0.07 to
      0.80), receiving a Pap smear during the same visit as CBE (OR = 0.45; 95% CI =
      0.27 to 0.72), and with increasing chronic disease comorbidity (P(trend) = .08).
      CONCLUSION: Screening CBE as performed in the community may be insufficiently
      sensitive to detect most lethal breast cancers. Low sensitivity of screening CBE
      in community practice may be partly attributable to its performance alongside
      time-consuming clinical tasks such as Pap smear screening or chronic illness
      care.

PMID- 16287889
TI  - Race and ethnicity: comparing medical records to self-reports.
AB  - Understanding and eliminating health disparities requires accurate data on
      race/ethnicity. To assess the quality of race/ethnicity data, we compared medical
      record classifications to self-report of a study of prophylactic mastectomy. A
      total of 788 women had race/ethnicity from both sources; 69.9% were 55 years of
      age or older, 38.3% were at least college graduates, and 67.8% were married or
      living with someone. There were 817 race/thnicity classifications for the 788
      women, of which 758 (92.3%) were identical in the medical record and self-report.
      Sensitivity and positive predictive value were high (86.7%-97.2%) for whites,
      Asians, and blacks and moderate (64.0% and 68.1%) for Latinas. However, only one
      of 18 Native Americans was correctly identified in her medical record. Our
      results indicate that even if the overall accuracy of medical record
      classifications for race/ethnicity is high, such a finding may obscure
      substantial inaccuracies in the recording for racial/ethnic minorities,
      especially Latinas and Native Americans.

PMID- 16287890
TI  - Relationship between tobacco control policies and the delivery of smoking
      cessation services in nonprofit HMOs.
AB  - BACKGROUND: This project examined tobacco policies and delivery of cessation
      services in nonprofit HMOs that collectively provide comprehensive medical care
      to more than 8 million members. METHODS: Three annual surveys with health plan
      managers showed that all of these health plans had written tobacco control
      guidelines that became more comprehensive over the span of this study. We also
      surveyed a random sample of 4207 current smokers who had attended a primary care
      visit in the past year (399-528 at each of nine health plans). RESULTS: Of these
      smokers, 71% reported advice to quit, 56% were asked about their willingness to
      quit, 49% were provided some assistance in quitting (mostly self-help material or
      information about classes or counseling), and 9% were offered some kind of follow
      up. Smokers receiving assistance in quitting reported higher satisfaction with
      their care. CONCLUSIONS: In general, health plans with the most comprehensive
      policies also showed higher rates of implementing tobacco treatment programs in
      primary care. Compared with tobacco control efforts of a decade or more ago,
      considerable progress has been made. However, there is still room for improvement
      in the proportion of smokers who receive the most effective forms of assistance
      in quitting.

PMID- 16287891
TI  - Creating standard cost measures across integrated health care delivery systems.
AB  - BACKGROUND: Economic analyses are increasingly important in medical research.
      Accuracy often requires that they include large, diverse populations, which
      requires data from multiple sources. The difficulty is in making the data
      comparable across different settings. This article focuses on how to create
      comparable measures of health care resource use and cost using data from seven
      health plans and delivery systems participating in the Cancer Research Network's
      HMOs Investigating Tobacco study. METHODS: We used a data inventory to identify
      variation in data capture across sites and used data dictionaries to develop
      algorithms for assigning standardized cost to the three major components of
      health care use: outpatient, inpatient, and pharmacy. RESULTS: The plans included
      in this study varied from fully integrated, closed-panel models to plans and
      delivery systems that include network or independent physician association
      components. Information derived from the data inventory and data dictionary
      instruments demonstrated a substantial variation in both the content and capture
      of data across all sites and across all components of usage. The methods we
      employed for cost allocation varied by usage component and were based on our
      ability to leverage the data points available to best reflect actual resource
      use. CONCLUSIONS: The importance of this article is the method of ascertaining,
      cataloging, and addressing the within- and between-plan differences in health
      care resource use. Second, the decisions we made to address the differences
      between health plans provide other researchers a starting point when creating a
      cost algorithm for multisite retrospective research.

PMID- 16287892
TI  - Disparities and survival among breast cancer patients.
AB  - BACKGROUND: Although rates of survival for women with breast cancer have
      improved, the survival disparity between African American and white women in the
      United States has increased. PURPOSE: To determine whether this survival
      disparity persists in an insured population with access to medical care. METHODS:
      In this retrospective cohort study, we extracted data from the tumor registries
      of six nonprofit, integrated health care delivery systems affiliated with the
      Cancer Research Network and assessed the survival of African American (n = 2276)
      and white (n = 18 879) female enrollees who were diagnosed with invasive breast
      cancer from January 1, 1993, through December 31, 1998. Cox proportional hazards
      regression was used to estimate the death rate among African American women
      relative to that of white women after adjustment for potential explanatory
      factors including stage at diagnosis, tumor characteristics, and treatment.
      RESULTS: Five-year survival was lower for African American women (73.8%) than for
      white women (81.6%). African American women were less likely to have tumor
      characteristics with good prognosis. Controlling for age at diagnosis, stage,
      grade, tumor size, and estrogen and progesterone receptor status, the adjusted
      hazard rate ratio for African American women was 1.34 (95% confidence interval =
      1.22 to 1.46). Similar risks were found among women ages 20-49 and 50 and older.
      Controlling for treatment slightly lowered the hazard rate ratio to 1.31 (95%
      confidence interval = 1.20 to 1.43). CONCLUSIONS: Among women with invasive
      breast cancer, being insured and having access to medical care does not eliminate
      the survival disparity for African American women.

PMID- 16287893
TI  - Racial and age differences in colon examination surveillance following a
      diagnosis of colorectal cancer.
AB  - PURPOSE: The purpose of this analysis is to describe factors associated with
      colorectal surveillance following diagnosis and treatment of nonmetastatic
      colorectal cancer. METHODS: Subjects were identified as part of the HMO Cancer
      Research Network's study of colorectal cancer survivors. To be eligible for the
      main study, patients had to be part of the staff model components of health
      maintenance organizations in southeastern Michigan and Minnesota. Using
      computerized databases, individuals were identified who were 40 years or older
      with incident nonmetastatic colorectal cancer diagnosed between January 1, 1990,
      and December 31, 2000. Using data current through 2002, we analyzed the cohort
      using chi-square test statistics, life tables, and Cox proportional hazards
      models to understand variations in posttreatment surveillance practices. Subjects
      were followed up from date of diagnosis to date of recurrence, death,
      disenrollment from the health plan, or loss to follow-up, which ever came first.
      We assessed factors associated with colorectal surveillance at 1, 3, and 5 years
      after treatment. We also included an analysis comparing those who received an
      exam and those who didn't regardless of exam timing. RESULTS: A total of 908
      patients were eligible for the main study. Of these, we excluded subjects who
      were not white or African American (n = 27), resulting in an analytic sample of
      881 (97% of the eligible cohort). Twenty-five percent of subjects were African
      American, 43% were female, and 48% were aged 70 years or older. The proportion
      who received an exam at 1 year was 18%, at 3 years was 60%, and at 5 years was
      67%. Chi-square tests showed that African Americans were statistically
      significantly less likely than whites to receive an exam at all three time
      points. The Cox proportional hazards model for examinations regardless of timing
      and adjusted for confounders showed that African Americans were still less likely
      than whites to receive an exam (hazard ratio = 0.62; 95% confidence interval [CI]
      = 0.51 to 0.75). The same trend in undersurveillance was also observed for those
      80 years of age or older at diagnosis, with an adjusted hazard ratio of 0.39 (95%
      CI = 0.26 to 0.57). CONCLUSION: Our data indicate that colorectal cancer
      survivors who are African American or aged 80 years or more at diagnosis are less
      likely to receive posttreatment colorectal surveillance. Whether these
      differences are due to system or patient level barriers needs further study.

PMID- 16287894
TI  - Participation of Asian-American women in cancer treatment research: a pilot
      study.
AB  - Few Asian-American women participate in cancer treatment trials. In a pilot study
      to assess barriers to participation, we mailed surveys to 132 oncologists and
      interviewed 19 Asian-American women with cancer from Northern California. Forty
      four oncologists responded. They reported as barriers language problems, lack of
      culturally relevant cancer information, and complex protocols. Most stated that
      they informed Asian-American women about treatment trials. Only four women
      interviewed knew about trials. Other patient-identified barriers were fear of
      side effects, language problems, competing needs, and fear of experimentation.
      Family decision making was a barrier for both oncologists and patients. Compared
      to non-Asian oncologists, more Asian oncologists have referred Asian-American
      women to industry trials and identified barriers similar to patients' reports.
      Our findings indicate that Asian-American women need to be informed about cancer
      treatment trials, linguistic barriers should be addressed, and future research
      should evaluate cultural barriers such as family decision making.

PMID- 16287896
TI  - Health system responses to the Women's Health Initiative findings on estrogen and
      progestin: organizational response.
AB  - Recent randomized trials have indicated that the risks of hormone therapy for
      menopausal women may outweigh the benefits. The purpose of this study was to
      describe how health plans responded to the findings of the Women's Health
      Initiative (WHI) estrogen plus progestin trial. We surveyed five health plans
      affiliated with the HMO Research Network and the Cancer Research Network to
      document the response of each plan to the WHI in terms of patient and provider
      education and guidelines. Every health plan issued responses within 3 months of
      WHI's termination in a variety of formats. Recommendations were relatively
      consistent across the organizations. Given the documented changes in hormone
      therapy use in these five health plans in the post-WHI era, we conclude that
      attempts on the part of each organization to educate patients and providers about
      the implications of the WHI may have contributed to the observed changes in
      hormone therapy use.

PMID- 16287895
TI  - Changes in women's use of hormones after the Women's Health Initiative estrogen
      and progestin trial by race, education, and income.
AB  - BACKGROUND: We examined the impact of race, education, and household income on
      changes in rates of discontinuation and initiation of hormone therapy before and
      after release of the Women's Health Initiative estrogen plus progestin trial
      results. METHODS: We conducted an observational cohort study of 221 378 women
      aged 40-80 years enrolled in five health maintenance organizations to estimate
      the prevalence and rates of discontinuation and initiation of estrogen plus
      progestin and estrogen only between September 1, 1999, to June 31, 2002
      (baseline), and December 31, 2002 (follow-up). We identified the census block
      group for each participant by geocoding her 2003 residential address. We
      categorized women into racial, education, and income groups based on the
      distribution of these characteristics in her community from year 2000 census data
      and the distributions of these characteristics within her HMO. RESULTS: There
      were significant differences in estrogen plus progestin and estrogen only
      prevalence by race, education level, and household income, and in estrogen plus
      progestin initiation by race and education level, but not by household income at
      follow-up. However, there were no differences by community race, education, or
      household income in change in the prevalence of either hormone therapy use at
      follow-up or in the rates of hormone therapy discontinuation or initiation from
      baseline to follow-up. CONCLUSIONS: Given the wide spread media attention to the
      Women's Health Initiative estrogen plus progestin trial results, our findings
      suggest comparable dissemination of this information across diverse socioeconomic
      groups.

PMID- 16287897
TI  - An automated data algorithm to distinguish screening and diagnostic colorectal
      cancer endoscopy exams.
AB  - Despite questions about accuracy, automated data are used increasingly for
      research and quality measurement. The goal of this study was to develop an
      automated data algorithm designed to distinguish screening and diagnostic
      endoscopy (sigmoidoscopy and colonoscopy) exams. We assessed the algorithm's
      ability to correctly classify the exams using paper medical records as the "gold
      standard." The algorithm used diagnostic codes to identify the indication of the
      endoscopies. The algorithm's ability to classify the indication varied by
      endoscopy exam. The sensitivities for identifying diagnostic sigmoidoscopy and
      colonoscopy were 48.1% and 23.8%, respectively. The algorithm missed most of the
      diagnostic endoscopies. Conversely, the sensitivities for identifying screening
      sigmoidoscopy and colonoscopy were high (87.9% and 84.4%, respectively) but were
      associated with low specificities. Our findings suggest that studies relying
      solely on automated data overestimate screening rates if indication is not
      considered. The automated algorithm presented here needs further improvements to
      better differentiate screening from diagnostic exams.

PMID- 16287899
TI  - Effect of breast feeding on risk of coeliac disease: a systematic review and meta
      analysis of observational studies.
AB  - BACKGROUND: Coeliac disease (CD) is a disorder that may depend on genetic,
      immunological, and environmental factors. Recent observational studies suggest
      that breast feeding may prevent the development of CD. AIM: To evaluate articles
      that compared effects of breast feeding on risk of CD. METHODS: Systematic review
      and meta-analysis of observational studies published between 1966 and June 2004
      that examined the association between breast feeding and the development of CD.
      RESULTS: Six case-control studies met the inclusion criteria. With the exception
      of one small study, all the included studies found an association between
      increasing duration of breast feeding and decreased risk of developing CD. Meta
      analysis showed that the risk of CD was significantly reduced in infants who were
      breast feeding at the time of gluten introduction (pooled odds ratio 0.48, 95% CI
      0.40 to 0.59) compared with infants who were not breast feeding during this
      period. CONCLUSIONS: Breast feeding may offer protection against the development
      of CD. Breast feeding during the introduction of dietary gluten, and increasing
      duration of breast feeding were associated with reduced risk of developing CD. It
      is, however, not clear from the primary studies whether breast feeding delays the
      onset of symptoms or provides a permanent protection against the disease. Long
      term prospective cohort studies are required to investigate further the relation
      between breast feeding and CD.

PMID- 16287898
TI  - Long-oligomer microarray profiling in Neurospora crassa reveals the
      transcriptional program underlying biochemical and physiological events of
      conidial germination.
AB  - To test the inferences of spotted microarray technology against a biochemically
      well-studied process, we performed transcriptional profiling of conidial
      germination in the filamentous fungus, Neurospora crassa. We first constructed a
      70 base oligomer microarray that assays 3366 predicted genes. To estimate the
      relative gene expression levels and changes in gene expression during conidial
      germination, we analyzed a circuit design of competitive hybridizations
      throughout a time course using a Bayesian analysis of gene expression level.
      Remarkable consistency of mRNA profiles with previously published northern data
      was observed. Genes were hierarchically clustered into groups with respect to
      their expression profiles over the time course of conidial germination. A
      functional classification database was employed to characterize the global
      picture of gene expression. Consensus motif searches identified a putative
      regulatory component associated with genes involved in ribosomal biogenesis. Our
      transcriptional profiling data correlate well with biochemical and physiological
      processes associated with conidial germination and will facilitate functional
      predictions of novel genes in N.crassa and other filamentous ascomycete species.
      Furthermore, our dataset on conidial germination allowed comparisons to
      transcriptional mechanisms associated with germination processes of diverse
      propagules, such as teliospores of the phytopathogenic fungus Ustilago maydis and
      spores of the social amoeba Dictyostelium discoideum.

PMID- 16287900
TI  - The use of an anaesthetic simulator to assess single-use laryngoscopy equipment.
AB  - OBJECTIVE: To compare the view at simulated direct laryngoscopy obtained with a
      standard laryngoscope, with and without a disposable cover and a disposable
      laryngoscope blade. DESIGN: Randomized non-blinded comparison. SETTING: The high
      fidelity human patient simulator at the Scottish Clinical Simulation Centre.
      PARTICIPANTS: Thirty-two anaesthetists with between 11 months and 25 years of
      experience. INTERVENTIONS: A randomized comparison of ease of laryngoscopy with
      each laryngoscope option for simulated easy and difficult laryngoscopy. MAIN
      OUTCOME MEASURES: The best grade achievable at laryngoscopy (Cormack and Lehane
      grade) for each laryngoscope, for both easy and difficult laryngoscopy. RESULTS:
      For the easy setting, 34% (P = 0.001) of anaesthetists graded laryngoscopy more
      difficult with the covered laryngoscope, and 22% (P = 0.008) with the disposable
      laryngoscope considered laryngoscopy more difficult than with the standard
      laryngoscope. For the difficult simulator setting, 69% (P < 0.001) found
      laryngoscopy more difficult with the covered laryngoscope and 69% (P < 0.001)
      with the disposable laryngoscope, when compared with the standard laryngoscope.
      There was no difference between the laryngoscopy grades for the covered and
      disposable laryngoscope for either easy (P = 0.21) or difficult (P = 0.87)
      simulation. CONCLUSIONS: Single-use equipment, as presently recommended for
      tonsillectomy surgery by the UK Department of Health, makes laryngoscopy more
      difficult for anaesthetists.

PMID- 16287902
TI  - Are vascular function measurements ready for the clinic?

PMID- 16287901
TI  - Treatment of pancreatic carcinoma by adenoviral mediated gene transfer of
      vasostatin in mice.
AB  - BACKGROUND: Tumour growth is angiogenesis dependent and antiangiogenesis therapy
      may represent a promising therapeutic option. AIMS: To evaluate the inhibitory
      effect of vasostatin gene mediated by a replication deficient recombinant
      adenovirus (Ad) on human pancreatic cancer in vivo and to investigate the
      mechanism of action of vasostatin. METHODS: Human umbilical vein endothelium
      derived ECV304 cells were infected with Ad-vasostatin and Ad-lacZ, and compared
      with phosphate buffered saline (PBS). MTT (3,-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide) assay was used to estimate the proliferation of
      ECV304 cells; tube formation assay and choriallantoic membrane assay were used to
      evaluate angiogenesis in vivo and in vitro. Xenografted nude mice with pancreatic
      cancer were established to observe in vivo tumour growth suppression. Microvessel
      density revealed by CD31 immunohistochemical staining was measured. RESULTS:
      Growth and tube formation of ECV304 cells infected with Ad-vasostatin were
      suppressed significantly compared with cells infected with Ad-lacZ or cells
      treated with PBS. Neovascularisation in the Ad-vasostatin group was less than
      that in the PBS and Ad-lacZ groups, based on chorioallantoic membrane results.
      Volumes of pancreatic tumours in the Ad-vasostatin group were significantly
      smaller than those in the PBS and Ad-lacZ groups at the end of the treatment
      period. Microvessel density in the Ad-vasostatin group was significantly lower
      than that in the Ad-lacZ and PBS groups. CONCLUSION: The vasostatin gene mediated
      by adenovirus is efficient for gene therapy for pancreatic carcinoma. Suppression
      of vasostatin on proliferation of vascular endothelium cells and angiogenesis may
      account for its effect.

PMID- 16287903
TI  - Plant allometry, leaf nitrogen and phosphorus stoichiometry, and interspecific
      trends in annual growth rates.
AB  - BACKGROUND: Life forms as diverse as unicellular algae, zooplankton, vascular
      plants, and mammals appear to obey quarter-power scaling rules. Among the most
      famous of these rules is Kleiber's (i.e. basal metabolic rates scale as the three
      quarters power of body mass), which has a botanical analogue (i.e. annual plant
      growth rates scale as the three-quarters power of total body mass). Numerous
      theories have tried to explain why these rules exist, but each has been heavily
      criticized either on conceptual or empirical grounds. N,P-STOICHIOMETRY: Recent
      models predicting growth rates on the basis of how total cell, tissue, or
      organism nitrogen and phosphorus are allocated, respectively, to protein and rRNA
      contents may provide the answer, particularly in light of the observation that
      annual plant growth rates scale linearly with respect to standing leaf mass and
      that total leaf mass scales isometrically with respect to nitrogen but as the
      three-quarters power of leaf phosphorus. For example, when these relationships
      are juxtaposed with other allometric trends, a simple N,P-stoichiometric model
      successfully predicts the relative growth rates of 131 diverse C3 and C4 species.
      CONCLUSIONS: The melding of allometric and N,P-stoichiometric theoretical
      insights provides a robust modelling approach that conceptually links the
      subcellular 'machinery' of protein/ribosomal metabolism to observed growth rates
      of uni- and multicellular organisms. Because the operation of this 'machinery' is
      basic to the biology of all life forms, its allometry may provide a mechanistic
      explanation for the apparent ubiquity of quarter-power scaling rules.

PMID- 16287904
TI  - Stigma development and receptivity in almond (Prunus dulcis).
AB  - BACKGROUND AND AIMS: Fertilization is essential in almond production, and
      pollination can be limiting in production areas. This study investigated stigma
      receptivity under defined developmental stages to clarify the relationship
      between stigma morphology, pollen germination, tube growth and fruit set.
      METHODS: Light and scanning electron microscopy were employed to examine stigma
      development at seven stages of flower development ranging from buds that were
      swollen to flowers in which petals were abscising. Flowers at different stages
      were hand pollinated and pollen germination and tube growth assessed. Artificial
      pollinations in the field were conducted to determine the effect of flower age on
      fruit set. KEY RESULTS: Later stages of flower development exhibited greater
      stigma receptivity, i.e. higher percentages of pollen germination and more
      extensive tube growth occurred in older (those opened to the flat petal stage or
      exhibiting petal fall) than younger flowers. Enhanced stigma receptivity was
      associated with elongation of stigmatic papillae and increased amounts of
      stigmatic exudate that inundated papillae at later developmental stages. Field
      pollinations indicated that the stigma was still receptive and nut set was
      maintained in older flowers. CONCLUSIONS: Stigma receptivity in almond does not
      become optimal until flowers are past the fully open stage. The stigma is still
      receptive and fruit set is maintained in flowers even at the stage when petals
      are abscising. Strategies to enhance pollination and crop yield, including the
      timing and placement of honey bees, should consider the effectiveness of
      developmentally advanced flowers.

PMID- 16287905
TI  - Anatomical significance of the hygrochastic movement in Anastatica hierochuntica.
AB  - BACKGROUND AND AIMS: Unlike the dispersal mechanisms of many desert plants, the
      whole dead skeleton of Anastatica hierochuntica is involved in seed dispersal and
      preservation. This process depends on the hygrochastic nature of the lignified
      conducting tissue that bends when dry and straightens under wet conditions. An
      anatomical interpretation of this mechanical movement was investigated. METHODS:
      An anatomical study of the stem was conducted on the juvenile plants raised under
      different water treatments and on the branch-orders of adult A. hierochuntica
      size-classes. KEY RESULTS: In the juvenile stem of A. hierochuntica, the area of
      cortex, conducting tissue and pith increased with water availability. However,
      the hydraulic conductance decreased, resulting in a better withdrawal of water in
      water-stressed plants. The anatomical investigation of the hygrochastic mechanism
      revealed an asymmetric distribution of the cortical tissues, with the conducting
      tissues of the stem of juvenile and adult plants being larger in the lower side.
      The hydraulic conductance was better in the basal and middle branch-orders than
      the terminal ones, permitting better conductance of water to the subsequent
      branch-orders. CONCLUSIONS: The lignified conducting tissue of the whole stem,
      having a hygrochastic nature, controls the movement of the branches. The greater
      amount of conducting tissue associated with a higher density of wide xylem
      vessels was observed in the lower side of the stem as compared with the upper
      side. Consequently, the conducting tissue in the lower side of the stem was
      suggested to be more effective in the opening process of the curled dry branches
      through better and more rapid conductance of water. Alternatively, due to the few
      narrow xylem vessels in the upper side of the stem, it was likely that the
      conducting tissue in the upper side is more effective in the closing process by
      providing more rapid drying. The mechanical rise of water and the related
      hygrochastic efficiency were maximized in the basal and middle branch-orders that
      are mostly involved in the mechanical movement.

PMID- 16287906
TI  - Short photoperiod induces dormancy in Lotus (Nelumbo nucifera).
AB  - BACKGROUND AND AIMS: Lotus (Nelumbo nucifera) has been cultivated as an
      ornamental and food plant in Japan for more than 1000 years. As large areas are
      required for its cultivation (approximately 2 m2 per plant), physiological
      research, such as into the effect of environmental factors on dormancy, has not
      been well studied until recently. In this paper, seedlings were used to examine
      environmental factors affecting dormancy induction. METHODS: In a first
      experiment, seeds were sown from 6 April to 6 October at 2-month intervals, and
      cultivated for 2 months in an unheated greenhouse. In a second experiment, seeds
      were prepared for germination on 16 November and 16 May and the seedlings were
      grown at 25 or 30 degrees C under natural daylength in phytotron growth rooms.
      After 1 month, the seedlings were cultivated at 20, 25 or 30 degrees C for a
      further month. The number of leaves and rhizome branches on the main stem were
      counted, and growth of rhizomes on the main stem was calculated using a rhizome
      enlargement index (= maximum internode diameter/internode length) after 2 months
      of culture in both experiments. KEY RESULTS: Rhizomes elongated without
      enlargement when the seeds were sown in April and June. Sowing the seeds in
      August and October resulted in rhizome enlargement from the tenth and fifth
      internodes, respectively. Rhizomes enlarged in the November-sowing but elongated
      in the May-sowing irrespective of temperature treatments under natural daylength
      in the phytotron rooms. The seedlings cultivated from May at 25-30 degrees C for
      2 months had more leaves, and more rhizome branches and nodes than those
      cultivated from November. CONCLUSIONS: Short days led to induced dormancy in
      lotus.

PMID- 16287907
TI  - Alcohol consumption and suicide.
AB  - About 90% of people in Western countries use alcohol at some time in their lives,
      and 40% experience temporary or permanent alcohol-related impairment in some area
      of life as a result of drinking. Multiple sociocultural and environmental factors
      influence suicide rates, and thus studies conducted in one nation are not always
      applicable to other nations. Impulsivity and aggression are strongly implicated
      in suicidal behaviour. Constructs related to aggression and impulsivity confer
      additional risk for suicidal behaviour in people with alcohol dependence. Lower
      serotonin activity is tied to increased aggression/impulsivity, which in turn may
      enhance the probability of suicidal behaviour. Acute alcohol use is associated
      with suicide. Suicide completers have high rates of positive blood alcohol.
      Intoxicated people are more likely to attempt suicide using more lethal methods.
      Alcohol may be important in suicides among individuals with no previous
      psychiatric history. Alcohol dependence is an important risk factor for suicidal
      behaviour. Mood disorder is a more powerful risk factor for suicide among problem
      drinkers as age increases. All individuals with alcohol use disorders should be
      assessed for suicide, especially at the end of a binge or in the very early phase
      of withdrawal. Middle-age and older men with alcohol dependence and mood
      disorders are at particularly high risk.

PMID- 16287908
TI  - Does temporal artery biopsy influence the management of temporal arteritis?
AB  - BACKGROUND: Temporal arteritis (TA) is the commonest form of primary vasculitis.
      Symptoms are variable, and therefore the diagnosis (or exclusion) of TA is often
      difficult. Surgeons are frequently asked to perform a temporal artery biopsy
      (TAB), but whether the histological result actually influences clinical
      management is unclear. AIM: To assess whether, in routine clinical practice, a
      TAB affects clinical decision-making in patients with suspected TA. DESIGN:
      Retrospective audit. METHODS: All patients who underwent a TAB in a single
      hospital over a 2-year period were identified. This included patients referred
      from different specialist departments. Individual patient records were examined
      to document the TAB result, and in particular, the timings of commencement and
      discontinuation of corticosteroid therapy. RESULTS: A total of 44 patients were
      included. TAB was positive in seven patients and negative in 37. In 31, there was
      no change in their clinical management despite a negative biopsy result: 18
      continued with corticosteroids for >6 months with a clinical diagnosis of TA, and
      in 13 patients a decision to stop steroids, or an alternative diagnosis, was made
      before the biopsy result was known. DISCUSSION: In this retrospective study, only
      a small number of TABs provided positive histological confirmation of TA, and in
      most patients undergoing TAB, there was little evidence that clinical decision
      making with respect to corticosteroid therapy was influenced by the TAB result.

PMID- 16287909
TI  - Sero-epidemological survey on canine visceral leishmaniasis and the distribution
      of sandfly vectors in northwestern Turkey: prevention strategies for childhood
      visceral leishmaniasis.
AB  - Visceral leishmaniasis (VL) caused by Leishmania infantum, is an endemic disease
      in Aegean and Mediterranean Regions among humans and dogs. In this study, a sero
      epidemiological survey for VL and cutaneous leishmaniasis (CL), which both are
      sporadically reported in the region, were carried out in the villages of
      Eskisehir, Afyon, and Bilecik cities. The study was designed according to the
      location of the sporadic cases of VL and CL, and blood samples of 111 dogs were
      randomly collected. Lymph node aspiration samples were taken from dogs that have
      popliteal lymphadenopathy. Sand flies were also collected using CDC light traps
      in the several localities. The sera samples were screened using IFAT, ELISA, rk39
      ELISA and dip-stick tests for anti-Leishmania antibodies. A total of 15 (13.51
      per cent) dogs out of 111 were found to be seropositive by at least one of the
      tests. The seropositivity ratios among dogs were found to be 27.5 per cent
      (8/29), 9.09 per cent (4/44) and 7.8 per cent (3/38) in Afyon, Bilecik and
      Eskisehir cities respectively. Leishmania amastigotes were detected in 4 of the
      14 lymph node aspiration samples (eight seronegative, six seropositive), and all
      of them were seropositive dogs. One year later, two of the dogs were found to be
      dead and the other two were severely ill. Among the 179 collected Phlebotomus
      specimens from, Phlebotomus major was found to be abundant (35.7 per cent) and
      the other species were P. simici (28.5 per cent), P. similis (34.7 per cent) and
      P. alexandri (1.1 per cent). In the study area, canine VL is more spread than
      human VL. Because dogs are playing an important role for VL in Mediterranean
      Basin, and development of appropriate control measures will be necessary for
      childhood VL.

PMID- 16287910
TI  - Renal transplantation in Slovenia after joining Eurotransplant.
AB  - BACKGROUND: This report presents data on renal transplantation in Slovenia before
      and after joining Eurotransplant (ET). METHODS: Slovenia (population: 2 million)
      has one renal transplant centre. The establishment of an appropriate national
      transplantation organization resulted in an increase in transplantations and the
      acceptance of Slovenia into ET at the beginning of 2000. Current
      immunosuppression is composed of cyclosporin (Neoral), mycophenolate mofetil,
      methylprednisolone and anti-interleukin-2 receptor monoclonal antibodies.
      RESULTS: By the end of 2004, 607 renal transplantations had been performed. From
      1970 to 1998, 124 patients were given living related donor kidneys. From 1986 to
      1999, 239 patients received renal grafts from deceased donors. From 2000 to 2004,
      244 patients were transplanted from deceased donors. In 2004, 55 renal
      transplantations were carried out. One hundred and forty one (57.8%) renal grafts
      were shipped from other ET countries. The HLA-antigen mismatch of 2.8+/-1.1 was
      not significantly different from what it was before 2000. Up to 31 December 2004,
      the 1- and 3-year patient survival rates were 98.3% and 96.0%, respectively. The
      concomitant graft survival rates were 95.8% and 93.5%, respectively. CONCLUSIONS:
      In the ET era, the number of deceased donor renal transplants per year was 2.8
      times higher than in the 14 years before. In 2004, we reached the average number
      of deceased donor renal transplants per million population of ET. Although tissue
      compatibility in these recipients was not significantly better than it was before
      the ET era, it would have been much worse had we not joined ET. Short- and medium
      term results in the ET era have been entirely comparable to those in large
      reports.

PMID- 16287911
TI  - Rho/Rho-kinase and C-reactive protein relationship in hypertension and
      atherosclerosis.

PMID- 16287913
TI  - Eurotransplant kidney allocation system (ETKAS): rationale and implementation.

PMID- 16287912
TI  - Calcification and the usual suspect phosphate: still guilty but there are other
      guys behind the scenes.

PMID- 16287914
TI  - What serum calcium can tell us and what it can't.

PMID- 16287915
TI  - Ex vivo CD(+) T-cell cytokine expression from patients with Sjogren's syndrome
      following in vitro stimulation to induce proliferation.
AB  - OBJECTIVE: To assess ex vivo CD4(+) T-cell cytokine expression from patients with
      primary Sjogren's syndrome (SS) following in vitro stimulation to induce
      proliferation, as proliferation is closely related to differentiation of cytokine
      producing cells. METHODS: Peripheral blood mononuclear cells (PBMCs) separated
      from primary SS patients (n = 28) and controls (n = 25) were analysed. PBMCs were
      stimulated with concanavalin A followed by phorbol 12-myristate 13-acetate and
      ionomycin. Intracellular interferon-gamma (IFN-gamma) and interleukin-4 (IL)-4 in
      proliferating CD4(+) T cells were assessed by flow cytometry. The proportion of
      cytokine-producing cells and proliferating cells in each division cycle was
      assessed using [5(and 6)-carboxyfluorescein diacetate, succinimidyl ester]
      labelled CD4(+/-) T cells. RESULTS: The proportion of IFN-gamma+ proliferating
      CD4(+) T cells in each cell division cycle from extraglandular SS was increased
      in glandular SS patients compared glandular SS patients with controls (P<0.05
      approximately 0.01). The percentage of IFN-gamma single positive proliferating
      CD4(+) T cells was greater in extraglandular SS patients (26.7+/-14.1%) compared
      with glandular SS (9.9 +/- 9.1%) (P<0.01) and controls (9.4 +/- 5.8%) (P<0.001).
      There was no significant difference in the percentages of IL-4(+) proliferating
      CD4(+) T cells among the groups. However, the proliferating response of CD4(+) T
      cells was significantly decreased in extraglandular SS patients (percentage of
      proliferating cells 38.4 +/- 18.6%) compared with that in glandular SS patients
      (64.2 +/- 17.2%) (P<0.05) and controls (63.1+/-10.6%) (P<0.01). CONCLUSIONS:
      CD4(+) T cells from extraglandular SS patients may have a predisposition for
      entry into the IFN-gamma-producing effector pathway as a result of the
      stimulations. These results are helpful for understanding the immunological
      difference between glandular and extraglandular SS and the mechanisms of disease
      progression.

PMID- 16287916
TI  - Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in
      ankylosing spondylitis: MMP-3 is a reproducibly sensitive and specific biomarker
      of disease activity.
AB  - OBJECTIVE: To submit serum levels of matrix metalloproteinases (MMPs) and tissue
      inhibitors of metalloproteinases (TIMPs) to statistical analyses to test their
      exact degrees of clinical usefulness as biomarkers for detecting high disease
      activity in ankylosing spondylitis (AS), comparing them with erythrocyte
      sedimentation rate (ESR) and C-reactive protein (CRP). METHODS: Serum levels of
      MMP-1, -3, -9 and TIMP-1 and -2 were measured in 42 AS patients and 20 healthy
      controls. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
      provided the gold standard for measuring disease activity. Patients with BASDAI >
      or =4 were regarded as having high disease activity. The results were compared
      with results for a separate cohort of 41 AS patients. RESULTS: Only MMP-3 levels
      were significantly higher in AS patients than in healthy controls (P<0.001).
      Within AS patients, MMP-3 levels were also higher in patients with high disease
      activity compared with those with low disease activity, and correlated
      significantly with BASDAI (r = 0.366, P = 0.017) and functional indices (r =
      0.344, P = 0.026). The correlation with BASDAI was stable in a 1-yr follow-up (r
      = 0.464, P = 0.095) and reproducible with two different enzyme-linked
      immunosorbent assays. For detecting high disease activity, the sensitivity and
      specificity of MMP-3 level was 69.2 and 68.8% respectively. Most importantly,
      using receiver operating characteristic plots to analyse the two cohorts, MMP-3
      was more accurate than ESR and CRP in detecting AS patients with high disease
      activity (P = 0.01 and P = 0.009, respectively). CONCLUSION: Using several
      analytical approaches that have never been reported previously, we showed that
      MMP-3 is a more useful biomarker than ESR and CRP to detect high disease activity
      in AS.

PMID- 16287917
TI  - Anti-CCP antibodies measured at disease onset help identify seronegative
      rheumatoid arthritis and predict radiological and functional outcome.
AB  - OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been
      identified as highly specific for rheumatoid arthritis (RA). Studies suggest an
      association with radiographic outcome. The aims of this study were to assess the
      diagnostic and prognostic utility of the second-generation anti-CCP(2) test in a
      large cohort of early RA patients compared with connective tissue disease (CTD)
      controls. METHODS: One hundred and eighty-two patients with RA and 121 patients
      with CTD were recruited. All RA patients had less than 24 months of symptoms and
      had CRP, rheumatoid factor (RF), HLA typing (SE) and anti-CCP(2) antibodies
      measured at baseline. Function was assessed using the Health Assessment
      Questionnaire (HAQ) and X-rays performed at 0, 12 and 24 months. RESULTS: The
      anti-CCP(2) antibody test demonstrated a specificity of 91% and sensitivity of
      81% for RA when compared with controls. In RF-negative patients, specificity was
      92% and sensitivity 60%. Baseline demographics of the RA cohort showed mean age
      57 yr, mean symptom duration 7 months, 63% RF-positive patients, 72% SE-positive,
      81% CCP-positive and 21% erosive. The only predictor of change in Larsen score
      from 0 to 24 months in the cohort was the presence of the shared epitope (P<0.05)
      and in the RF-negative subgroup it was CCP(2) antibody titre >100 (P<0.05).
      Baseline HAQ was the only significant predictor of HAQ at 24 months, but in the
      RF-negative subgroup CCP(2) antibody titre >100 predicted a poor functional
      response at 24 months (P<0.05). CONCLUSIONS: This study confirms the diagnostic
      utility of anti-CCP(2) antibodies in early RA, particularly in seronegative
      patients, in whom anti-CCP(2) positivity also conferred prognostic utility for
      radiographic and functional outcomes.

PMID- 16287918
TI  - Conditioning of cartilage during normal activities is an important factor in the
      development of osteoarthritis.
AB  - Mechanical factors have long been implicated in the aetiology of osteoarthritis
      (OA). The two most popular hypotheses regarding the mechanism of cartilage damage
      are: the application of too high a stress and the mechanism of fatigue.
      Mechanical failure in any material, however, can be caused by either or both of
      these mechanisms. It is hypothesized that, because cartilage is a living tissue,
      the threshold at which it fails by either mechanism is regulated by the prevalent
      stresses arising in a joint. As these stresses are determined by activities and
      lifestyles, a low failure threshold can be the result of prolonged periods of low
      level activity, which, if interrupted with short periods of intense activities,
      can subject weakened cartilage to damaging stresses. Were this hypothesis proven,
      it would address difficulties encountered with these hypotheses and explain some
      clinical observations. It would also have implications for the activities and
      lifestyles of individuals.

PMID- 16287919
TI  - Influence of methotrexate, TNF blockers and prednisolone on antibody responses to
      pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To compare antibody responses to 23-valent pneumococcal vaccine
      (Pneumovax) in controls and patients with established rheumatoid arthritis (RA)
      treated with TNF blockers, methotrexate (MTX) or a combination of both. METHODS:
      Patients with RA (n = 149) and healthy controls (n = 47) were vaccinated.
      Treatment with TNF blockers (etanercept or infliximab) and MTX was given to 50
      patients, and 62 patients were treated with TNF blockers alone or with other
      DMARDs. MTX alone was given to 37 patients. Concentrations of immunoglobulin G
      (IgG) antibodies against pneumococcal capsular polysaccharides 23F and 6B were
      measured by enzyme-linked immunoassay before and 4-6 weeks after vaccination. An
      immune response was defined as a twofold or higher increase in antibody
      concentration following vaccination. RESULTS: Prevaccination antibody levels for
      both 23F and 6B were similar in the patient groups. Antibody concentrations after
      vaccination increased significantly in all groups. Patients treated with TNF
      blockers without MTX showed better immune responses than those treated with TNF
      blockers in combination with MTX (P = 0.037 for 23F and P = 0.004 for 6B) or MTX
      alone (P<0.001 for both 23F and 6B). RA patients given MTX alone had the lowest
      immune responses. Prednisolone treatment did not influence the responses.
      CONCLUSIONS: Patients treated with TNF blockers and controls showed similar
      responses to vaccination. In contrast, patients treated with MTX had reduced
      responses regardless of anti-TNF treatment. The findings do not argue against the
      use of pneumococcal vaccination in RA patients undergoing treatment with TNF
      blockers.

PMID- 16287920
TI  - Clinical significance of quantitative immunohistology in labial salivary glands
      for diagnosing Sjogren's syndrome.
AB  - OBJECTIVES: Because patients with primary Sjogren's syndrome (pSS) are at risk of
      developing other autoimmune phenomena and malignant lymphoma, it is important to
      distinguish pSS from non-Sjogren's (nSS) sicca syndrome. However, this
      distinction might be difficult because of the lack of a gold standard for pSS. We
      studied the clinical significance of quantitative immunohistology (QIH) in labial
      salivary glands for diagnosing pSS. METHODS: In a model mimicking the making of a
      clinical diagnosis, five experts diagnosed 396 patients as nSS, 'indefinite', pSS
      or secondary SS (sSS) using 25 clinical parameters. Patients were diagnosed
      twice, namely without (yielding gold-standard diagnoses) and with knowledge of
      QIH. The numbers of changes in diagnosis from 'indefinite' to 'definite' (nSS,
      pSS or sSS) or vice versa were compared. Patient groups with vs without a changed
      diagnosis in the four gold-standard diagnosis groups were compared regarding
      objective autoimmune parameters. RESULTS: Sensitivity, specificity, positive and
      negative predictive value for abnormal QIH in pSS vs nSS were 93, 86, 76 and 96%,
      respectively. Changes in diagnosis from 'indefinite' to 'definite' (31%) were
      found more often (P = 0.00) than changes from 'definite' to 'indefinite' (10%).
      Knowledge of QIH distinguished patient groups within the gold-standard nSS,
      indefinite and pSS patient group with regard to autoimmune parameters.
      CONCLUSION: In view of the consequences of distinguishing pSS from nSS, these
      results point to an additional diagnostic role for QIH in clinical practice.

PMID- 16287921
TI  - Inhibition of COX-2 by celecoxib in the canine groove model of osteoarthritis.
AB  - OBJECTIVE: In vitro studies showed a beneficial effect of celecoxib on
      proteoglycan turnover and content of osteoarthritic cartilage. In the present
      study we evaluated whether these favourable effects of celecoxib could also be
      demonstrated in vivo. METHODS: In 24 Beagle dogs, osteoarthritis (OA) was induced
      in one knee according to the groove model. The animals were divided into three
      groups and received oral placebo or 100 or 200 mg celecoxib daily, starting
      directly after surgery. After 15 weeks joint tissue from all dogs was analysed.
      RESULTS: Induction of OA resulted in macroscopic and histological damage of
      cartilage, changes in cartilage proteoglycan turnover, loss of cartilage matrix
      proteoglycans and slight synovial inflammation, all characteristic of early OA.
      Surprisingly, none of the parameters was significantly changed upon celecoxib
      treatment. Synovial fluid prostaglandin E(2) levels were dose-dependently
      diminished by celecoxib, demonstrating that the celecoxib had reached the joint
      in sufficient amounts. Using an in vitro setup, canine cartilage under
      degenerative conditions was favourably influenced by celecoxib, demonstrating
      that canine cartilage is sensitive to celecoxib. CONCLUSION: The present study
      showed a chondroneutral effect of celecoxib on the characteristics of
      experimentally induced OA in vivo, in contrast to the observed beneficial effect
      in vitro. It could be that celecoxib had been beneficial to degenerated cartilage
      in vivo but that these effects were counteracted by increased loading of the
      affected joint and the associated progression of OA, occurring because of the
      well-known analgesic effects of celecoxib.

PMID- 16287922
TI  - Forefoot joint damage, pain and disability in rheumatoid arthritis patients with
      foot complaints: the role of plantar pressure and gait characteristics.
AB  - OBJECTIVE: To assess (i) the relationship between forefoot joint damage and foot
      function (expressed as gait and pressure parameters), (ii) the relationship
      between foot function and pain, and (iii) the relationship between foot function
      and disability in patients with foot complaints secondary to rheumatoid arthritis
      (RA). METHODS: Sixty-two patients with RA-related foot complaints were included.
      Measurements of joint damage, gait characteristics, plantar pressure, pain and
      disability were obtained. Data were analysed using descriptive and correlational
      techniques. RESULT: s. Joint damage on radiographs of the forefoot correlated
      significantly with forefoot pressure (r = 0.296, P = 0.020). Further
      investigation of the metatarsophalangeal joints (MTPs) showed joint damage to
      correlate significantly with peak pressure and pressure-time integral (PTI) of
      MTP1 and MTP4. A significant correlation between PTI under the forefoot and
      barefoot pain was found (r = 0.290, P = 0.022). Gait parameters (total contact
      time and the duration of heel loading) and disability, measured with the Foot
      Function Index, were significantly correlated (r = 0.315, P = 0.013 and r =
      0.266, P = 0.037, respectively). CONCLUSION: Forefoot joint damage in the
      rheumatoid foot is related to increased pressure under the forefoot, especially
      pressure under the first and fourth MTP joints. High forefoot pressure is
      associated with pain during barefoot walking. A prolonged stance phase and
      delayed heel lift are related to disability in daily activities.

PMID- 16287923
TI  - Competence-based assessment of specialist registrars: evaluation of a new
      assessment of out-patient consultations.
AB  - OBJECTIVE: To implement and evaluate formal assessment of the performance of West
      Midlands rheumatology specialist registrars (SpRs) in conducting out-patient
      consultations. METHODS: SpRs conducted a full out-patient clinic while being
      observed by one or two consultants who scored each SpR's performance on a
      structured pro forma. The assessment was conducted within the examining
      consultant's hospital trust (in which the SpR was not working). The process was
      evaluated by trainees and trainers by means of a questionnaire. RESULTS: Sixteen
      SpRs were assessed. No trainee failed to reach the required standard. Six
      trainees scored 'borderline' for management planning and four had a borderline
      performance recorded for examination skills. Overall the process was valued by
      trainers and trainees, although consensus was that it would be more practicable
      for the trainee to be examined within the hospital in which they were working by
      a visiting consultant examiner. It was also felt that a broader range of scoring
      options would be preferable. CONCLUSION: Formal assessment, by direct
      observation, of the skills of SpRs in conducting an out-patient clinic is
      practicable and offers information which is useful to trainer and trainee. A
      culture of direct observation of performance can be achieved within the context
      of rheumatology higher medical training.

PMID- 16287924
TI  - Interleukin-10 gene polymorphisms are associated with the SLICC/ACR Damage Index
      in systemic lupus erythematosus.
AB  - OBJECTIVE: Overproduction of interleukin-10 (IL-10) is a pivotal feature in the
      pathophysiology of systemic lupus erythematosus (SLE). We examined the IL10
      genotype of Korean patients with SLE and normal controls to determine whether
      associations exist between the pattern of inherited IL10 genes and SLE
      susceptibility or the SLICC/ACR Damage Index (SDI). METHODS: A total of 350
      Korean SLE patients and 330 healthy subjects were enrolled. Direct DNA sequencing
      and primer extension procedures were employed. Logistic regression analyses were
      performed to examine the genetic association with SLE and SDI. RESULTS: Eight
      sequence variants were identified by direct DNA sequencing in 24 Korean
      individuals. Five of the polymorphisms were selected for larger scale genotyping
      (n = 680) by considering their allele frequencies, haplotype-tagging status and
      linkage disequilibrium coefficients among polymorphisms. Haplotypes and allele
      distributions of the IL10 polymorphisms did not differ significantly between SLE
      patients and controls. Among identified SNPs, the rare C allele of IL10-592A-->C
      was significantly associated with the SDI among SLE patients in the following
      three alternative models: codominant (P = 0.007, odds ratio = 1.70), dominant (P
      = 0.02, odds ratio = 1.85) and recessive (P = 0.05, odds ratio = 2.25).
      Similarly, IL10+955T-->G and IL10-ht2 were significantly associated with the SDI
      in the codominant and dominant models. CONCLUSION: IL10 polymorphisms are not
      associated with disease susceptibility in Korean patients with SLE. However, IL10
      592A-->C, IL10+955T-->G and IL10-ht2 are significantly associated with the SDI,
      suggesting that IL10-592C, IL10+955G and IL10-ht2 accelerate the damage induced
      by SLE.

PMID- 16287925
TI  - Comparison of the Health Assessment Questionnaire (HAQ) and the modified HAQ
      (MHAQ) in patients with rheumatoid arthritis.
AB  - OBJECTIVES: Physical disability in patients with rheumatoid arthritis (RA) is
      often assessed by questionnaires. We compared the Health Assessment Questionnaire
      (HAQ) with the modified HAQ (MHAQ) in a cohort of RA patients across various
      levels of disability, and examined correlations with other measures of physical
      function. METHODS: Patients with RA (n = 182) completed self-report
      questionnaires assessing functional capacity. Instruments included the MHAQ and
      HAQ completed separately, as well as SF-36 and the Arthritis Impact Measurement
      Scales (AIMS). Scores from unadjusted and adjusted HAQ were compared with MHAQ at
      various disability levels. RESULTS: A clear ceiling effect with aggregation of
      normal scores for physical function was observed for MHAQ (23%) and HAQ (12%),
      but not for SF-36 (4%) or AIMS (5%). The correlations between adjusted/unadjusted
      HAQ and MHAQ scores were 0.85/0.88. A discrepancy in HAQ and MHAQ scores was
      observed in patients with high levels of disability, especially when MHAQ was
      compared with the adjusted final HAQ score. Adjustment of HAQ by aids or help
      increased the final score by an average of 0.15, and both adjusted and unadjusted
      HAQ scores were numerically clearly higher (mean 0.45 and 0.30, respectively)
      than the MHAQ score. CONCLUSION: The present findings indicate that MHAQ and HAQ
      may be applicable as measures of physical capacity in RA patients, but clinicians
      and researchers should select the appropriate instrument for the setting, and be
      aware of differences in scores, especially at different disability levels.

PMID- 16287926
TI  - The effect of foot orthoses in rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the effectiveness of foot orthoses using the foot function
      index (FFI) in a group of patients with rheumatoid arthritis (RA) during a period
      of 6 months. METHODS: Thirty-six rheumatoid subjects with foot pain were examined
      and appropriate foot orthoses were prescribed according to each patient's needs.
      All the patients were evaluated 30, 90 and 180 days after the baseline visit. FFI
      values, daily time of wearing the orthoses and adverse effects were noted at each
      appointment. The Stanford Health Assessment Questionnaire (HAQ) was used at the
      initial visit to evaluate the influence of physical condition on FFI response.
      RESULTS: With the use of foot orthoses, FFI values decreased in all subscales
      (pain, disability and activity limitation). This reduction was noted in the first
      month and was maintained throughout the trial. Those using EVA (ethyl-vinyl
      acetate; n = 28) orthoses presented results similar to those for the total group.
      Patients wearing made-to-measure orthoses (n = 8) exhibited higher initial FFI
      values and worse evolution during the trial, significant for pain and disability
      but not for activity limitation. Minor adverse reactions were noted; none
      required interruption of treatment. There was no relation between HAQ and FFI
      evolution. CONCLUSIONS: Foot orthoses were effective as an adjuvant in the
      management of rheumatoid foot. They significantly reduced pain, disability and
      activity limitation, as measured by the FFI, with minor adverse effects.

PMID- 16287927
TI  - Costs and course of disease and function in early rheumatoid arthritis: a 3-year
      follow-up (the Swedish TIRA project).
AB  - OBJECTIVE: To calculate direct and indirect costs and to study disease activity
      and functional ability over 3 yr in early rheumatoid arthritis (RA). METHODS:
      Three hundred and three patients with early (< or = 1 yr) RA were recruited
      during a period of 27 months (1996-1998). Data were recorded during 3 yr to
      assess disease activity, functional ability, medication, health-care utilization
      and days lost from work. RESULTS: Within 3 months, improvements were seen
      regarding all recorded variables assessing disease activity and functional
      ability, but 15% had sustained high or moderate disease activity throughout the
      study period. Indirect costs exceeded direct costs in all 3 yr. The average
      direct costs were 3704 Euros (3297 US Dollars) in year 1 and 2652 Euros ( 2360 US
      Dollars ) in year 3. All costs decreased, except those for medication and
      surgery. Compared with men, women had more ambulatory care visits and used more
      complementary medicine. The indirect costs were 8871 Euros ( 7895 US Dollars) in
      year 1 and remained essentially unchanged; this was similar for both sexes.
      Almost 50% were on sick leave or early retirement at inclusion. Sick leave
      decreased but was offset by an increase in early retirement. The 14 patients who
      eventually received TNF inhibitors incurred higher costs even before prescription
      of anti-TNF therapy. CONCLUSION: Disease activity and functional ability improved
      within 3 months after diagnosis of early RA. Direct costs decreased, except for
      medication and surgery. Indirect costs remained unchanged. Fifteen per cent of
      the patients had high or moderate disease activity in all 3 yr, indicating a need
      for more aggressive early anti-rheumatic therapy.

PMID- 16287928
TI  - Evidence for a differential association of the Arg200Trp single-nucleotide
      polymorphism in FRZB with hip osteoarthritis and osteoporosis.

PMID- 16287929
TI  - Self-referral of symptoms (SOS) follow-up system of appointments for patients
      with uncertain diagnoses in rheumatology out-patients.
AB  - OBJECTIVE: Clinical features in rheumatological conditions often fluctuate with
      time and this may cause difficulty when evaluating patients whose symptoms or
      signs do not coincide with their initial rheumatology visit. The aim of this
      study was to evaluate the outcome of a follow-up system whereby patients with
      uncertain rheumatological diagnoses at their initial assessment are given easy
      and rapid access to a rheumatology review. METHOD: We studied the outcome of SOS
      (self-referral of symptoms) appointments offered to patients over a 44-month
      period in one consultant's clinic at the Staffordshire Rheumatology Centre. The
      reattendance rates and diagnoses at the initial and subsequent visits were
      evaluated over a mean period of 26.3 months (range 7-64 months). RESULTS: Thirty
      seven patients (23 males, 14 females) were offered SOS appointments during the
      period studied. At the initial assessment, a provisional diagnosis was recorded
      for 29 patients (78.4%), whereas the diagnosis was unclear for the other eight
      patients. At the end of the study period, 10 patients (27%) had requested
      specialist review via the SOS system after a mean period of 6.8 months (1-19
      months). The diagnosis remained unchanged in 8 of the 10 reattenders, whereas the
      diagnosis was revised in two patients. None of these patients, however, developed
      an inflammatory arthritis. CONCLUSION: We suggest that an SOS system of
      appointments may be a feasible and practical method to follow up patients who
      have uncertain rheumatological diagnoses at their initial visit. This follow-up
      system may not easily fit into the current out-patient reforms being implemented
      in the National Health Service, yet this form of specialist follow-up seems
      clinically essential for some forms of disease management. The requirements
      necessary to operate such a system as well as the envisaged pros and cons for the
      patient and for the rheumatologist are discussed.

PMID- 16287930
TI  - Patient self-efficacy and health locus of control: relationships with health
      status and arthritis-related expenditure.
AB  - OBJECTIVE: To explore the relationship between measures of self-efficacy, health
      locus of control, health status and direct medical expenditure among community
      dwelling subjects with rheumatoid arthritis (RA) and osteoarthritis (OA).
      METHODS: This analysis is part of a larger ongoing study of the costs and
      outcomes of arthritis and its treatments. Community-dwelling RA and OA
      respondents completed questionnaires concerning arthritis-related expenditure,
      health status, arthritis related self-efficacy and health locus of control.
      RESULTS: Data were obtained from 70 RA respondents and 223 OA respondents. The
      majority of respondents were female with a mean age of 63 yr for RA respondents
      and 68 yr for OA respondents. Among the RA respondents, those with higher self
      efficacy reported better health status and lower overall costs. Health locus of
      control was not consistently correlated with health status. OA respondents with
      higher self-efficacy reported better health status and lower costs. Health locus
      of control had more influence. OA respondents with higher external locus of
      control reported worse pain and function. A higher belief in chance as a
      determinant of health was correlated with more visits to general practitioners
      and a higher cost to both the respondent and the health system. CONCLUSION:
      Higher self-efficacy, which is amenable to change through education programmes,
      was associated with better health status and lower costs to the respondent and
      the health system in this cross-sectional study. Locus of control had less of an
      influence; however, the tendency was for those with higher external locus of
      control to have higher costs and worse health status. As the measurement of these
      constructs is simple and the outcome potentially affects health status, these
      results have implications for future intervention studies to improve quality of
      life and reduce the financial impact of arthritis on both the health-care system
      and patients.

PMID- 16287931
TI  - Systemic cytokine levels and the effects of etanercept in TNF receptor-associated
      periodic syndrome (TRAPS) involving a C33Y mutation in TNFRSF1A.
AB  - OBJECTIVE: To investigate the levels of the pro-inflammatory cytokines IL-6, TNF
      alpha, IL-1beta, IL-8, IL-10 and IL-12p70 in the plasma of patients with TNF
      receptor-associated periodic syndrome (TRAPS) in relation to CRP levels and
      treatment with etanercept. METHODS: Cytokine concentrations were measured in
      sequential plasma samples obtained from eight patients with a C33Y mutation in
      TNFRSF1A and diagnosed with TRAPS, using cytokine bead array. The TRAPS samples
      were compared with samples from normal controls and rheumatoid arthritis
      patients. RESULTS: Levels of IL-6 were significantly elevated in C33Y TRAPS
      patients and these correlated with CRP levels in some of the patients. IL-8
      levels were also significantly elevated in the TRAPS patients. However, neither
      TNF-alpha nor IL-1beta demonstrated a similar increase. This differed from the
      patients with rheumatoid arthritis, for whom levels of IL-6, IL-8, TNF-alpha, IL
      1beta and IL-10 were significantly elevated. The levels of detectable TNF-alpha
      in the TRAPS patients' plasma were elevated during etanercept treatment.
      CONCLUSIONS: The cytokine profile of C33Y TRAPS differs from that of a typical
      autoimmune inflammatory condition such as rheumatoid arthritis, as only IL-6 and
      IL-8 were elevated in C33Y TRAPS patients, as distinct from a generalized
      elevation of pro-inflammatory cytokines. However, only some of the C33Y patients
      tested showed a relationship between elevated IL-6 and CRP. This is consistent
      with clinical observations that there is marked heterogeneity between individuals
      with TRAPS, including those in the same family cohort. Although etanercept has a
      therapeutic effect in some TRAPS patients, it induces increased plasma
      concentrations of TNF-alpha, possibly by increasing TNF-alpha stability.

PMID- 16287932
TI  - An efficient randomized algorithm for contact-based NMR backbone resonance
      assignment.
AB  - MOTIVATION: Backbone resonance assignment is a critical bottleneck in studies of
      protein structure, dynamics and interactions by nuclear magnetic resonance (NMR)
      spectroscopy. A minimalist approach to assignment, which we call 'contact-based',
      seeks to dramatically reduce experimental time and expense by replacing the
      standard suite of through-bond experiments with the through-space (nuclear
      Overhauser enhancement spectroscopy, NOESY) experiment. In the contact-based
      approach, spectral data are represented in a graph with vertices for putative
      residues (of unknown relation to the primary sequence) and edges for hypothesized
      NOESY interactions, such that observed spectral peaks could be explained if the
      residues were 'close enough'. Due to experimental ambiguity, several incorrect
      edges can be hypothesized for each spectral peak. An assignment is derived by
      identifying consistent patterns of edges (e.g. for alpha-helices and beta-sheets)
      within a graph and by mapping the vertices to the primary sequence. The key
      algorithmic challenge is to be able to uncover these patterns even when they are
      obscured by significant noise. RESULTS: This paper develops, analyzes and applies
      a novel algorithm for the identification of polytopes representing consistent
      patterns of edges in a corrupted NOESY graph. Our randomized algorithm aggregates
      simplices into polytopes and fixes inconsistencies with simple local
      modifications, called rotations, that maintain most of the structure already
      uncovered. In characterizing the effects of experimental noise, we employ an NMR
      specific random graph model in proving that our algorithm gives optimal
      performance in expected polynomial time, even when the input graph is
      significantly corrupted. We confirm this analysis in simulation studies with
      graphs corrupted by up to 500% noise. Finally, we demonstrate the practical
      application of the algorithm on several experimental beta-sheet datasets. Our
      approach is able to eliminate a large majority of noise edges and to uncover
      large consistent sets of interactions. AVAILABILITY: Our algorithm has been
      implemented in the platform-independent Python code. The software can be freely
      obtained for academic use by request from the authors.

PMID- 16287933
TI  - 2SNP: scalable phasing based on 2-SNP haplotypes.
AB  - 2SNP software package implements a new very fast scalable algorithm for haplotype
      inference based on genotype statistics collected only for pairs of SNPs. This
      software can be used for comparatively accurate phasing of large number of long
      genome sequences, e.g. obtained from DNA arrays. As an input 2SNP takes genotype
      matrix and outputs the corresponding haplotype matrix. On datasets across 79
      regions from HapMap 2SNP is several orders of magnitude faster than GERBIL and
      PHASE while matching them in quality measured by the number of correctly phased
      genotypes, single-site and switching errors. For example, 2SNP requires 41 s on
      Pentium 4 2 Ghz processor to phase 30 genotypes with 1381 SNPs (ENm010.7p15:2
      data from HapMap) versus GERBIL and PHASE requiring more than a week and
      admitting no less errors than 2SNP.

PMID- 16287934
TI  - Automatic assignment of biomedical categories: toward a generic approach.
AB  - MOTIVATION: We report on the development of a generic text categorization system
      designed to automatically assign biomedical categories to any input text. Unlike
      usual automatic text categorization systems, which rely on data-intensive models
      extracted from large sets of training data, our categorizer is largely data
      independent. METHODS: In order to evaluate the robustness of our approach we test
      the system on two different biomedical terminologies: the Medical Subject
      Headings (MeSH) and the Gene Ontology (GO). Our lightweight categorizer, based on
      two ranking modules, combines a pattern matcher and a vector space retrieval
      engine, and uses both stems and linguistically-motivated indexing units. RESULTS
      AND CONCLUSION: Results show the effectiveness of phrase indexing for both GO and
      MeSH categorization, but we observe the categorization power of the tool depends
      on the controlled vocabulary: precision at high ranks ranges from above 90% for
      MeSH to <20% for GO, establishing a new baseline for categorizers based on
      retrieval methods.

PMID- 16287935
TI  - Equivalent binding sites reveal convergently evolved interaction motifs.
AB  - MOTIVATION: Much research has been devoted to the characterization of interaction
      interfaces found in complexes with known structure. In this context, the
      interactions of non-homologous domains at equivalent binding sites are of
      particular interest, as they can reveal convergently evolved interface motifs.
      Such motifs are an important source of information to formulate rules for
      interaction specificity and to design ligands based on the common features shared
      among diverse partners. RESULTS: We develop a novel method to identify non
      homologous structural domains which bind at equivalent sites when interacting
      with a common partner. We systematically apply this method to all pairs of
      interactions with known structure and derive a comprehensive database for these
      interactions. Of all non-homologous domains, which bind with a common interaction
      partner, 4.2% use the same interface of the common interaction partner (excluding
      immunoglobulins and proteases). This rises to 16% if immunoglobulin and proteases
      are included. We demonstrate two applications of our database: first, the
      systematic screening for viral protein interfaces, which can mimic native
      interfaces and thus interfere; and second, structural motifs in enzymes and its
      inhibitors. We highlight several cases of virus protein mimicry: viral M3 protein
      interferes with a chemokine dimer interface. The virus has evolved the motif
      SVSPLP, which mimics the native SSDTTP motif. A second example is the regulatory
      factor Nef in HIV which can mimic a kinase when interacting with SH3. Among
      others the virus has evolved the kinase's PxxP motif. Further, we elucidate motif
      resemblances in Baculovirus p35 and HIV capsid proteins. Finally, chymotrypsin is
      subject to scrutiny wrt. its structural similarity to subtilisin and wrt. its
      inhibitor's similar recognition sites. SUPPLEMENTARY INFORMATION: A database is
      online at scoppi.biotec.tu-dresden.de/abac/.

PMID- 16287936
TI  - Highly consistent patterns for inherited human diseases at the molecular level.
AB  - Over 1600 mammalian genes are known to cause an inherited disorder, when
      subjected to one or more mutations. These disease genes represent a unique
      resource for the identification and quantification of relationships between
      phenotypic attributes of a disease and the molecular features of the associated
      disease genes, including their ascribed annotated functional classes and
      expression patterns. Such analyses can provide a more global perspective and a
      deeper understanding of the probable causes underlying human hereditary diseases.
      In this perspective and critical view of disease genomics, we present a
      comparative analysis of genes reported to cause inherited diseases in humans in
      terms of their causative effects on physiology, their genetics and inheritance
      modes, the functional processes they are involved in and their expression
      profiles across a wide spectrum of tissues. Our analysis reveals that there are
      more extensive correlations between these attributes of genetic disease genes
      than previously appreciated. For instance, the functional pattern of genes
      causing dominant and recessive diseases is markedly different. Also, the function
      of the genes and their expression correlate with the type of disease they cause
      when mutated. The results further indicate that a comparative genomics approach
      for the analysis of genes linked to human genetic diseases will facilitate the
      elucidation of the underlying molecular and cellular mechanisms.

PMID- 16287937
TI  - Elucidation of directionality for co-expressed genes: predicting intra-operon
      termination sites.
AB  - MOTIVATION: In this paper, we present a novel framework for inferring regulatory
      and sequence-level information from gene co-expression networks. The key idea of
      our methodology is the systematic integration of network inference and network
      topological analysis approaches for uncovering biological insights. RESULTS: We
      determine the gene co-expression network of Bacillus subtilis using Affymetrix
      GeneChip time-series data and show how the inferred network topology can be
      linked to sequence-level information hard-wired in the organism's genome. We
      propose a systematic way for determining the correlation threshold at which two
      genes are assessed to be co-expressed using the clustering coefficient and we
      expand the scope of the gene co-expression network by proposing the slope ratio
      metric as a means for incorporating directionality on the edges. We show through
      specific examples for B. subtilis that by incorporating expression level
      information in addition to the temporal expression patterns, we can uncover
      sequence-level biological insights. In particular, we are able to identify a
      number of cases where (1) the co-expressed genes are part of a single
      transcriptional unit or operon and (2) the inferred directionality arises due to
      the presence of intra-operon transcription termination sites. AVAILABILITY: The
      software will be provided on request. SUPPLEMENTARY INFORMATION:
      http://www.phys.psu.edu/~ralbert/pdf/gma_bioinf_supp.pdf

PMID- 16287938
TI  - Classification of microarray data with factor mixture models.
AB  - MOTIVATION: The classification of few tissue samples on a very large number of
      genes represents a non-standard problem in statistics but a usual one in
      microarray expression data analysis. In fact, the dimension of the feature space
      (the number of genes) is typically much greater than the number of tissues. We
      consider high-density oligonucleotide microarray data, where the expression level
      is associated to an 'absolute call', which represents a qualitative indication of
      whether or not a transcript is detected within a sample. The 'absolute call' is
      generally not taken in consideration in analyses. RESULTS: In contrast to
      frequently used cluster analysis methods to analyze gene expression data, we
      consider a problem of classification of tissues and of the variables selection.
      We adopted methodologies formulated by Ghahramani and Hinton and Rocci and Vichi
      for simultaneous dimensional reduction of genes and classification of tissues;
      trying to identify genes (denominated 'markers') that are able to distinguish
      between two known different classes of tissue samples. In this respect, we
      propose a generalization of the approach proposed by McLachlan et al. by advising
      to estimate the distribution of log LR statistic for testing one versus two
      component hypothesis in the mixture model for each gene considered individually,
      using a parametric bootstrap approach. We compare conditional (on 'absolute
      call') and unconditional analyses performed on dataset described in Golub et al.
      We show that the proposed techniques improve the results of classification of
      tissue samples with respect to known results on the same benchmark dataset.
      AVAILABILITY: The software of Ghahramani and Hinton is written in Matlab and
      available in 'Mixture of Factor Analyzers' on
      http://www.gatsby.ucl.ac.uk/~zoubin/software.html while the software of Rocci and
      Vichi is available upon request from the authors.

PMID- 16287939
TI  - PATIKAweb: a Web interface for analyzing biological pathways through advanced
      querying and visualization.
AB  - Patikaweb provides a Web interface for retrieving and analyzing biological
      pathways in the Patika database, which contains data integrated from various
      prominent public pathway databases. It features a user-friendly interface,
      dynamic visualization and automated layout, advanced graph-theoretic queries for
      extracting biologically important phenomena, local persistence capability and
      exporting facilities to various pathway exchange formats.

PMID- 16287940
TI  - Mean curvature as a major determinant of beta-sheet propensity.
AB  - MOTIVATION: Despite the importance of beta-sheets as building blocks in proteins
      and also toxic elements in the pathological disorders, ranging from Alzheimer's
      disease to mad cow disease, the principles underlying their stability are not
      well understood. Non-random beta-sheet propensities of amino acids have been
      revealed both by their distinct statistical preferences within known protein
      structures and by the relative thermodynamic scales through the experimental host
      guest systems. However, recent fitting analysis has proved that a native beta
      sheet conforms to a minimal surface with zero mean curvature, like the physical
      model of soap films. RESULTS: We here suggest that the stability of a residue in
      the all beta-sheet proteins can be measured with its mean curvature parameter,
      using discrete differential geometry. The sharply decreasing mean curvature with
      increasing number of beta-strands identifies a significant cooperative effect
      whereby the interstrand interaction increases in strength with the number of beta
      strands. Furthermore, strong correlations of mean curvatures with previous beta
      sheet propensities of amino acids show that their intrinsic differences in
      adopting the ideal beta-sheet structure are affected by the water-accessible area
      of side-chains, and result in the distinct statistical and thermodynamic beta
      sheet propensities. Therefore, we conclude that mean curvature should be
      considered as the significant stability index of a beta-sheet structure.

PMID- 16287942
TI  - Improved prediction of bacterial transcription start sites.
AB  - MOTIVATION: Identifying bacterial promoters is an important step towards
      understanding gene regulation. In this paper, we address the problem of
      predicting the location of promoters and their transcription start sites (TSSs)
      in Escherichia coli. The accepted method for this problem is to use position
      weight matrices (PWMs), which define conserved motifs at the sigma-factor binding
      site. However this method is known to result in large numbers of false positive
      predictions. RESULTS: Our approaches to TSS prediction are based upon an ensemble
      of support vector machines (SVMs) employing a variant of the mismatch string
      kernel. This classifier is subsequently combined with a PWM and a model based on
      distribution of distances from TSS to gene start. We investigate the effect of
      different scoring techniques and quantify performance using area under a
      detection-error tradeoff curve. When tested on a biologically realistic task, our
      method provides performance comparable with or superior to the best reported for
      this task. False positives are significantly reduced, an improvement of great
      significance to biologists. AVAILABILITY: The trained ensemble-SVM model with
      instructions on usage can be downloaded from
      http://eresearch.fit.qut.edu.au/downloads

PMID- 16287941
TI  - WindowMasker: window-based masker for sequenced genomes.
AB  - MOTIVATION: Matches to repetitive sequences are usually undesirable in the output
      of DNA database searches. Repetitive sequences need not be matched to a query, if
      they can be masked in the database. RepeatMasker/Maskeraid (RM), currently the
      most widely used software for DNA sequence masking, is slow and requires a
      library of repetitive template sequences, such as a manually curated RepBase
      library, that may not exist for newly sequenced genomes. RESULTS: We have
      developed a software tool called WindowMasker (WM) that identifies and masks
      highly repetitive DNA sequences in a genome, using only the sequence of the
      genome itself. WM is orders of magnitude faster than RM because WM uses a few
      linear-time scans of the genome sequence, rather than local alignment methods
      that compare each library sequence with each piece of the genome. We validate WM
      by comparing BLAST outputs from large sets of queries applied to two versions of
      the same genome, one masked by WM, and the other masked by RM. Even for genomes
      such as the human genome, where a good RepBase library is available, searching
      the database as masked with WM yields more matches that are apparently non
      repetitive and fewer matches to repetitive sequences. We show that these results
      hold for transcribed regions as well. WM also performs well on genomes for which
      much of the sequence was in draft form at the time of the analysis. AVAILABILITY:
      WM is included in the NCBI C++ toolkit. The source code for the entire toolkit is
      available at ftp://ftp.ncbi.nih.gov/toolbox/ncbi_tools++/CURRENT/. Once the
      toolkit source is unpacked, the instructions for building WindowMasker
      application in the UNIX environment can be found in file
      src/app/winmasker/README.build. SUPPLEMENTARY INFORMATION: Supplementary data are
      available at
      ftp://ftp.ncbi.nlm.nih.gov/pub/agarwala/windowmasker/windowmasker_suppl.pdf

PMID- 16287944
TI  - Ramping up rehabilitation research urged as a "public health imperative".

PMID- 16287943
TI  - The cover. The Sick Patient.

PMID- 16287945
TI  - 1918 killer flu virus reconstructed, may help prevent future outbreaks.

PMID- 16287946
TI  - Policy targets lowering SIDS incidence.

PMID- 16287947
TI  - Pesticide exposure at schools and acute illnesses.

PMID- 16287948
TI  - Arginine metabolism, pulmonary hypertension, and sickle cell disease.

PMID- 16287949
TI  - Role of vitamin E in the prevention of cardiovascular disease and cancer.

PMID- 16287950
TI  - Arginine metabolism, pulmonary hypertension, and sickle cell disease.

PMID- 16287951
TI  - Smoking cessation.

PMID- 16287952
TI  - Smoking cessation.

PMID- 16287953
TI  - Trends in house calls to Medicare beneficiaries.

PMID- 16287954
TI  - High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after
      myocardial infarction: the IDEAL study: a randomized controlled trial.
AB  - CONTEXT: Evidence suggests that more intensive lowering of low-density
      lipoprotein cholesterol (LDL-C) than is commonly applied clinically will provide
      further benefit in stable coronary artery disease. OBJECTIVE: To compare the
      effects of 2 strategies of lipid lowering on the risk of cardiovascular disease
      among patients with a previous myocardial infarction (MI). DESIGN, SETTING, AND
      PARTICIPANTS: The IDEAL study, a prospective, randomized, open-label, blinded end
      point evaluation trial conducted at 190 ambulatory cardiology care and specialist
      practices in northern Europe between March 1999 and March 2005 with a median
      follow-up of 4.8 years, which enrolled 8888 patients aged 80 years or younger
      with a history of acute MI. INTERVENTIONS: Patients were randomly assigned to
      receive a high dose of atorvastatin (80 mg/d; n = 4439), or usual-dose
      simvastatin (20 mg/d; n = 4449). MAIN OUTCOME MEASURE: Occurrence of a major
      coronary event, defined as coronary death, confirmed nonfatal acute MI, or
      cardiac arrest with resuscitation. RESULTS: During treatment, mean LDL-C levels
      were 104 (SE, 0.3) mg/dL in the simvastatin group and 81 (SE, 0.3) mg/dL in the
      atorvastatin group. A major coronary event occurred in 463 simvastatin patients
      (10.4%) and in 411 atorvastatin patients (9.3%) (hazard ratio [HR], 0.89; 95% CI,
      0.78-1.01; P = .07). Nonfatal acute MI occurred in 321 (7.2%) and 267 (6.0%) in
      the 2 groups (HR, 0.83; 95% CI, 0.71-0.98; P = .02), but no differences were seen
      in the 2 other components of the primary end point. Major cardiovascular events
      occurred in 608 and 533 in the 2 groups, respectively (HR, 0.87; 95% CI, 0.77
      0.98; P = .02). Occurrence of any coronary event was reported in 1059 simvastatin
      and 898 atorvastatin patients (HR, 0.84; 95% CI, 0.76-0.91; P<.001).
      Noncardiovascular death occurred in 156 (3.5%) and 143 (3.2%) in the 2 groups
      (HR, 0.92; 95% CI, 0.73-1.15; P = .47). Death from any cause occurred in 374
      (8.4%) in the simvastatin group and 366 (8.2%) in the atorvastatin group (HR,
      0.98; 95% CI, 0.85-1.13; P = .81). Patients in the atorvastatin group had higher
      rates of drug discontinuation due to nonserious adverse events; transaminase
      elevation resulted in 43 (1.0%) vs 5 (0.1%) withdrawals (P<.001). Serious
      myopathy and rhabdomyolysis were rare in both groups. CONCLUSIONS: In this study
      of patients with previous MI, intensive lowering of LDL-C did not result in a
      significant reduction in the primary outcome of major coronary events, but did
      reduce the risk of other composite secondary end points and nonfatal acute MI.
      There were no differences in cardiovascular or all-cause mortality. Patients with
      MI may benefit from intensive lowering of LDL-C without an increase in
      noncardiovascular mortality or other serious adverse reactions.Trial Registration
      ClinicalTrials.gov Identifier: NCT00159835.

PMID- 16287955
TI  - Efficacy and safety of edifoligide, an E2F transcription factor decoy, for
      prevention of vein graft failure following coronary artery bypass graft surgery:
      PREVENT IV: a randomized controlled trial.
AB  - CONTEXT: Coronary artery bypass graft (CABG) surgery with autologous vein
      grafting is commonly performed. Progressive neointimal hyperplasia, however,
      contributes to considerable vein graft failure. Edifoligide is an oligonucleotide
      decoy that binds to and inhibits E2F transcription factors and thus may prevent
      neointimal hyperplasia and vein graft failure. OBJECTIVE: To assess the efficacy
      and safety of pretreating vein grafts with edifoligide for patients undergoing
      CABG surgery. DESIGN, SETTING, AND PARTICIPANTS: A phase 3 randomized, double
      blind, placebo-controlled trial of 3014 patients undergoing primary CABG surgery
      with at least 2 planned saphenous vein grafts and without concomitant valve
      surgery, who were enrolled between August 2002 and October 2003 at 107 US sites.
      INTERVENTION: Vein grafts were treated ex vivo with either edifoligide or placebo
      in a pressure-mediated delivery system. The first 2400 patients enrolled were
      scheduled for 12- to 18-month follow-up angiography. MAIN OUTCOME MEASURES: The
      primary efficacy end point was angiographic vein graft failure (> or =75% vein
      graft stenosis) occurring 12 to 18 months after CABG surgery. Other end points
      included other angiographic variables, adverse events through 30 days, and major
      adverse cardiac events. RESULTS: A total of 1920 patients (80%) either died (n =
      91) or underwent follow-up angiography (n = 1829). Edifoligide had no effect on
      the primary end point of per patient vein graft failure (436 [45.2%] of 965
      patients in the edifoligide group vs 442 [46.3%] of 955 patients in the placebo
      group; odds ratio, 0.96 [95% confidence interval {CI}, 0.80-1.14]; P = .66), on
      any secondary angiographic end point, or on the incidence of major adverse
      cardiac events at 1 year (101 [6.7%] of 1508 patients in the edifoligide group vs
      121 [8.1%] of 1506 patients in the placebo group; hazard ratio, 0.83 [95% CI,
      0.64-1.08]; P = .16). CONCLUSIONS: Failure of at least 1 vein graft is quite
      common within 12 to 18 months after CABG surgery. Edifoligide is no more
      effective than placebo in preventing these events. Longer-term follow-up and
      additional research are needed to determine whether edifoligide has delayed
      beneficial effects, to understand the mechanisms and clinical consequences of
      vein graft failure, and to improve the durability of CABG surgery. Clinical Trial
      Registration ClinicalTrials.gov Identifier: NCT00042081.

PMID- 16287956
TI  - Effects of protein, monounsaturated fat, and carbohydrate intake on blood
      pressure and serum lipids: results of the OmniHeart randomized trial.
AB  - CONTEXT: Reduced intake of saturated fat is widely recommended for prevention of
      cardiovascular disease. The type of macronutrient that should replace saturated
      fat remains uncertain. OBJECTIVE: To compare the effects of 3 healthful diets,
      each with reduced saturated fat intake, on blood pressure and serum lipids.
      DESIGN, SETTING, AND PARTICIPANTS: Randomized, 3-period, crossover feeding study
      (April 2003 to June 2005) conducted in Baltimore, Md, and Boston, Mass.
      Participants were 164 adults with prehypertension or stage 1 hypertension. Each
      feeding period lasted 6 weeks and body weight was kept constant. INTERVENTIONS: A
      diet rich in carbohydrates; a diet rich in protein, about half from plant
      sources; and a diet rich in unsaturated fat, predominantly monounsaturated fat.
      MAIN OUTCOME MEASURES: Systolic blood pressure and low-density lipoprotein
      cholesterol. RESULTS: Blood pressure, low-density lipoprotein cholesterol, and
      estimated coronary heart disease risk were lower on each diet compared with
      baseline. Compared with the carbohydrate diet, the protein diet further decreased
      mean systolic blood pressure by 1.4 mm Hg (P = .002) and by 3.5 mm Hg (P = .006)
      among those with hypertension and decreased low-density lipoprotein cholesterol
      by 3.3 mg/dL (0.09 mmol/L; P = .01), high-density lipoprotein cholesterol by 1.3
      mg/dL (0.03 mmol/L; P = .02), and triglycerides by 15.7 mg/dL (0.18 mmol/L;
      P<.001). Compared with the carbohydrate diet, the unsaturated fat diet decreased
      systolic blood pressure by 1.3 mm Hg (P = .005) and by 2.9 mm Hg among those with
      hypertension (P = .02), had no significant effect on low-density lipoprotein
      cholesterol, increased high-density lipoprotein cholesterol by 1.1 mg/dL (0.03
      mmol/L; P = .03), and lowered triglycerides by 9.6 mg/dL (0.11 mmol/L; P = .02).
      Compared with the carbohydrate diet, estimated 10-year coronary heart disease
      risk was lower and similar on the protein and unsaturated fat diets. CONCLUSION:
      In the setting of a healthful diet, partial substitution of carbohydrate with
      either protein or monounsaturated fat can further lower blood pressure, improve
      lipid levels, and reduce estimated cardiovascular risk. Clinical Trials
      Registration ClinicalTrials.gov Identifier: NCT00051350.

PMID- 16287957
TI  - Molecular classification of patients with unexplained hamartomatous and
      hyperplastic polyposis.
AB  - CONTEXT: Significant proportions of patients with hamartomatous polyposis or with
      hyperplastic/mixed polyposis remain without specific clinical and molecular
      diagnosis or present atypically. Assigning a syndromic diagnosis is important
      because it guides management, especially surveillance and prophylactic surgery.
      OBJECTIVE: To systematically classify patients with unexplained hamartomatous or
      hyperplastic/mixed polyposis by extensive molecular analysis in the context of
      central rereview of histopathology results. DESIGN, SETTING, AND PATIENTS:
      Prospective, referral-based study of 49 unrelated patients from outside
      institutions (n = 28) and at a comprehensive cancer center (n = 21), conducted
      from May 2, 2002, until December 15, 2004. Germline analysis of PTEN, BMPR1A,
      STK11 (sequence, deletion), SMAD4, and ENG (sequence), specific exon screening of
      BRAF, MYH, and BHD, and rereview of polyp histology results were performed. MAIN
      OUTCOME MEASURES: Molecular, clinical, and histopathological findings in patients
      with unexplained polyposis. RESULTS: Of the 49 patients, 11 (22%) had germline
      mutations. Of 14 patients with juvenile polyposis, 2 with early-onset disease had
      mutations in ENG, encoding endoglin, previously only associated with hereditary
      hemorrhagic telangiectasia; 1 had hemizygous deletion encompassing PTEN and
      BMPR1A; and 1 had an SMAD4 mutation. One individual previously classified with
      Peutz-Jeghers syndrome had a PTEN deletion. Among 9 individuals with an unknown
      hamartomatous polyposis, 4 had mutations in STK11 (1), BMPR1A (2), and SMAD4 (1).
      Of the 23 patients with hyperplastic/mixed polyposis, 2 had PTEN mutations.
      Substantial discrepancies in histopathology results were seen. CONCLUSIONS:
      Systematic molecular classification of 49 patients with unexplained hamartomatous
      or hyperplastic polyposis uncovered a potential novel susceptibility gene, ENG,
      for juvenile polyposis. Importantly, given the substantial proportion of patients
      found to have germline mutations, more extensive analysis of the known
      susceptibility genes is indicated. Rereview of histology results by a dedicated
      gastrointestinal pathologist should be considered routinely, as organ-specific
      surveillance rests on defining syndromic diagnosis.

PMID- 16287958
TI  - Pregnancy characteristics and maternal risk of breast cancer.
AB  - CONTEXT: During pregnancy, serum levels of estrogen, progesterone, and other
      hormones are markedly higher than during other periods of life. Pregnancy
      hormones primarily are produced in the placenta, and signs of placental
      impairment may serve as indirect markers of hormone exposures during pregnancy.
      During pregnancy, these markers have been inconsistently associated with
      subsequent risk of breast cancer in the mother. OBJECTIVE: To examine
      associations between indirect markers of hormonal exposures, such as placental
      weight and other pregnancy characteristics, and maternal risk of developing
      breast cancer. DESIGN AND SETTING: Population-based cohort study using data from
      the Swedish Birth Register, the Swedish Cancer Register, the Swedish Cause of
      Death Register, and the Swedish Register of Population and Population Changes.
      PARTICIPANTS: Women included in the Sweden Birth Register who delivered
      singletons between 1982 and 1989, with complete information on date of birth and
      gestational age. Women were followed up until the occurrence of breast cancer,
      death, or end of follow-up (December 31, 2001). Cox proportional hazards models
      were used to estimate associations between hormone exposures and risks of breast
      cancer. MAIN OUTCOME MEASURE: Incidence of invasive breast cancer. RESULTS: Of
      314,019 women in the cohort, 2216 (0.7%) developed breast cancer during the
      follow-up through 2001, of whom 2100 (95%) were diagnosed before age 50 years.
      Compared with women who had placentas weighing less than 500 g in 2 consecutive
      pregnancies, the risk of breast cancer was increased among women whose placentas
      weighed between 500 and 699 g in their first pregnancy and at least 700 g in
      their second pregnancy (or vice versa) (adjusted hazard ratio, 1.82; 95%
      confidence interval [CI], 1.07-3.08), and the corresponding risk was doubled
      among women whose placentas weighed at least 700 g in both pregnancies (adjusted
      hazard ratio, 2.05; 95% CI, 1.15-3.64). A high birth weight (> or =4000 g) in 2
      successive births was associated with an increased risk of breast cancer before
      but not after adjusting for placental weight and other covariates (adjusted
      hazard ratio, 1.10; 95% CI, 0.76-1.59). CONCLUSIONS: Placental weight is
      positively associated with maternal risk of breast cancer. These results further
      support the hypothesis that pregnancy hormones are important modifiers of
      subsequent maternal breast cancer risk.

PMID- 16287959
TI  - Adrenal insufficiency.
AB  - A 44-year-old woman reported several weeks of fatigue, somnolence, pain in the
      large joints, nausea, and decreased appetite. She had also noted an unintentional
      11-kg weight loss over a period of 6 months. She had a remote history of
      amenorrhea, but she was presently menstruating regularly. She was taking no
      medications, with the exception of acetaminophen as needed for knee pain. The
      diagnosis of adrenal insufficiency (AI) was considered. Serum cortisol level
      after adrenocorticotropin hormone (ACTH) stimulation was abnormal. Because her
      plasma ACTH level was not increased, a diagnosis of secondary AI (due to
      deficiency in ACTH) was made. Magnetic resonance imaging of the brain performed
      to exclude the presence of a sellar or suprasellar mass showed reduction in size
      of the pituitary gland and an increased cerebrospinal fluid content within the
      sella, consistent with a partially empty sella. The patient's symptoms improved
      rapidly with hydrocortisone therapy but during follow-up, the dose of
      hydrocortisone was found to be excessive. Important differences exist between
      primary and secondary AI, and the diagnosis of secondary AI may be challenging.
      The therapy of AI should be carefully tailored to the requirements of the
      individual patient.

PMID- 16287960
TI  - Why America needs a strong FDA.

PMID- 16287961
TI  - The IDEAL cholesterol: lower is better.

PMID- 16287962
TI  - Gene therapy and vein graft patency in coronary artery bypass graft surgery.

PMID- 16287963
TI  - More novel effects of diet on blood pressure and lipids.

PMID- 16287965
TI  - JAMA patient page. Adrenal insufficiency.

PMID- 16287964
TI  - Unwinding the heterogeneous nature of hamartomatous polyposis syndromes.

PMID- 16287966
TI  - Negative regulation of nuclear divisions in Caenorhabditis elegans by
      retinoblastoma and RNA interference-related genes.
AB  - Short RNA regulatory molecules, microRNAs, and short interfering RNAs participate
      in a range of developmental gene networks by base-pairing with their target
      sequences. Consistent with these findings, genes required for the biogenesis and
      function of short interfering RNAs and microRNAs, dicer (dcr-1 in Caenorhabditis
      elegans) and argonaute homologs, are essential for development in diverse
      organisms, including C. elegans. We demonstrate that genes required for the
      function of short RNAs synergize with the retinoblastoma tumor suppressor homolog
      lin-35 in negative regulation of the nuclear divisions in the intestine of C.
      elegans. The level of cyclin E (cye-1) expression is critical for nuclear
      divisions in the intestine and is elevated in double mutants in lin-35 and RNA
      interference pathway genes. We propose that RNA interference-related pathways
      cooperate with retinoblastoma in transcriptional repression of endogenous genes,
      an example being cyclin E.

PMID- 16287967
TI  - Anxiolytic- and antidepressant-like profiles of the galanin-3 receptor (Gal3)
      antagonists SNAP 37889 and SNAP 398299.
AB  - The neuropeptide galanin mediates its effects through the receptor subtypes
      Gal(1), Gal(2), and Gal(3) and has been implicated in anxiety- and depression
      related behaviors. Nevertheless, the receptor subtypes relevant to these
      behaviors are not known because of the lack of available galanin-selective
      ligands. In this article, we use behavioral, neurochemical, and
      electrophysiological approaches to investigate the anxiolytic- and antidepressant
      like effects of two potent small-molecule, Gal(3)-selective antagonists, SNAP
      37889 and the more soluble analog SNAP 398299. Acute administration of SNAP 37889
      or SNAP 398299 enhanced rat social interaction. Furthermore, acute SNAP 37889 was
      also shown to reduce guinea pig vocalizations after maternal separation, to
      attenuate stress-induced hyperthermia in mice, to increase punished drinking in
      rats, and to decrease immobility and increase swimming time during forced swim
      tests with rats. Moreover, SNAP 37889 increased the social interaction time after
      14 days of treatment and maintained its antidepressant effects during forced swim
      tests with rats after 21 days of treatment. In microdialysis studies, SNAP 37889
      partially antagonized the galanin-evoked reduction in hippocampal serotonin (5
      hydroxytryptamine, 5-HT), as did the 5-HT(1A) receptor antagonist WAY100635.
      Their combination produced a complete reversal of the effect of galanin. SNAP
      398299 partially reversed the galanin-evoked inhibition of dorsal raphe cell
      firing and galanin-evoked hyperpolarizing currents. These results indicate that
      Gal(3)-selective antagonists produce anxiolytic- and antidepressant-like effects,
      possibly by attenuating the inhibitory influence of galanin on 5-HT transmission
      at the level of the dorsal raphe nucleus.

PMID- 16287968
TI  - Small molecules that reactivate p53 in renal cell carcinoma reveal a NF-kappaB
      dependent mechanism of p53 suppression in tumors.
AB  - Renal cell carcinomas (RCC) commonly retain wild-type but functionally inactive
      p53, which is repressed by an unknown dominant mechanism. To help reveal this
      mechanism, we screened a diverse chemical library for small molecules capable of
      restoring p53-dependent transactivation in RCC cells carrying a p53-responsive
      reporter. Among the compounds isolated were derivatives of 9-aminoacridine (9AA),
      including the antimalaria drug quinacrine, which strongly induced p53 function in
      RCC and other types of cancer cells. Induction of p53 by these compounds does not
      involve genotoxic stress and is mediated by suppression of NF-kappaB activity. In
      contrast to agents that target IkappaB kinase 2, 9AA and quinacrine can
      effectively suppress both basal and inducible activities of NF-kappaB,
      representing inhibitors of a previously undescribed type that convert NF-kappaB
      from a transactivator into a transrepressor, leading to accumulation of inactive
      nuclear complexes with unphosphorylated Ser-536 in the p65/RelA subunit. p53
      function in RCC can be restored by ectopic expression of a superrepressor of
      IkappaB as effectively as by 9AA-derived compounds. These findings suggest that
      the complete or partial repression of p53 observed in many tumors can be the
      result of constitutive activation of NF-kappaB. The results demonstrate, in
      principle, the possibility to kill cancer cells selectively through simultaneous
      inhibition of NF-kappaB and activation of p53 by a single small molecule and
      suggest anticancer applications for the well known antimalaria drug quinacrine.

PMID- 16287969
TI  - Adaptive shift in the domain of negative stiffness during spontaneous oscillation
      by hair bundles from the internal ear.
AB  - When a hair cell of the bullfrog's sacculus is maintained in vitro under native
      ionic conditions, its mechanosensitive hair bundle may oscillate spontaneously.
      This movement has been hypothesized to result from the interaction of the
      bundle's negative stiffness, which creates a region of mechanical instability,
      with a myosin-based adaptation mechanism that continually repositions the bundle
      there. To test this proposition, we used a flexible stimulus fiber in an analog
      feedback loop to measure the displacement-force relation of an oscillating hair
      bundle. A digital signal processor was used to monitor spontaneous oscillations
      in real time and trigger measurements at particular phases of the movement cycle.
      By comparing the displacement-force curves obtained at the two extremes of a hair
      bundle's motion, we demonstrated a shift in the negative-stiffness region whose
      direction, orientation, magnitude, and kinetics agreed with the predictions of
      the gating-spring theory. The results are in accordance with the idea that
      adaptation underlies spontaneous hair-bundle oscillation, and therefore powers
      the active process that also amplifies and tunes the hair cell's mechanical
      responsiveness.

PMID- 16287970
TI  - Target site localization by site-specific, DNA-binding proteins.

PMID- 16287971
TI  - Probing structural heterogeneities and fluctuations of nucleic acids and
      denatured proteins.
AB  - We study protein and nucleic acid structure and dynamics using single-molecule
      FRET and alternating-laser excitation. Freely diffusing molecules are sorted into
      subpopulations based on single-molecule signals detected within 100 micros to 1
      ms. Distance distributions caused by fluctuations faster than 100 micros are
      studied within these subpopulations by using time-correlated single-photon
      counting. Measured distance distributions for dsDNA can be accounted for by
      considering fluorophore linkers and fluorophore rotational diffusion, except that
      we find smaller fluctuations for internally labeled dsDNA than DNA with one of
      the fluorophores positioned at a terminal site. We find that the electrostatic
      portion of the persistence length of short single-stranded poly(dT) varies
      approximately as the ionic strength (I) to the -1/2 power (I(-1/2)), and that the
      average contribution to the contour length per base is 0.40-0.45 nm. We study
      unfolded chymotrypsin inhibitor 2 (CI2) and unfolded acyl-CoA binding protein
      (ACBP) even under conditions where folded and unfolded subpopulations coexist
      (contributions from folded proteins are excluded by using alternating-laser
      excitation). At lower denaturant concentrations, unfolded CI2 and ACBP are more
      compact and display larger fluctuations than at higher denaturant concentrations
      where only unfolded proteins are present. The experimentally measured
      fluctuations are larger than the fluctuations predicted from a Gaussian chain
      model or a wormlike chain model. We propose that the larger fluctuations may
      indicate transient residual structure in the unfolded state.

PMID- 16287972
TI  - Suppressor of cytokine signaling-1 selectively inhibits LPS-induced IL-6
      production by regulating JAK-STAT.
AB  - Suppressor of cytokine signaling-1 (SOCS-1) is one of the negative-feedback
      regulators of Janus kinase (JAK)-signal transducer and activator of transcription
      (STAT) signaling. We previously showed that SOCS-1 participates in LPS signaling,
      but it is not entirely clear yet how SOCS-1 suppresses LPS signaling. In this
      study, we demonstrate that SOCS-1 selectively inhibits LPS-induced IL-6
      production through regulation of JAK-STAT but not production of TNF-alpha,
      granulocyte colony-stimulating factor, IFN-beta, and other cytokines. We found
      that LPS directly activated Jak2 and Stat5, whereas SOCS-1 inhibited LPS-induced
      Jak2 and Stat5 activation. Furthermore, AG490, a Jak-specific inhibitor, and
      dominant negative Stat5 only reduced LPS-induced IL-6 production. Additionally,
      Stat5 interacted with p50, resulting in recruitment of Stat5 to the IL-6 promoter
      together with p50 in response to LPS stimulation. These findings suggest that the
      JAK-STAT pathway participates in LPS-induced IL-6 production and that SOCS-1
      suppresses LPS signaling by regulating JAK-STAT.

PMID- 16287973
TI  - CD4+CD25+ regulatory T cells limit the risk of autoimmune disease arising from T
      cell receptor crossreactivity.
AB  - The molecular-mimicry theory proposes that immune crossreactivity between
      microbial and self-antigen is the initiating event in the activation of
      autoaggressive immune responses leading to autoimmune disease. In support of this
      possibility, it is now accepted that T cell recognition of antigen is highly
      degenerate. However, it is to be expected that the immune system would have
      evolved mechanisms to counter such a potential danger. We studied the influence
      of CD4(+)CD25(+) regulatory T cells (Treg) on the ability of suboptimal T cell
      receptor ligands to provoke autoimmunity. By using CD4(+) T cell-driven
      experimental autoimmune encephalomyelitis as a model, it was found that depletion
      of CD4(+)CD25(+)Foxp3(+) Treg allowed pathology to develop in response to
      suboptimal T cell stimulation. These data demonstrate the importance of Treg in
      raising the threshold of triggering of autoreactive T cell responses, thus
      limiting the risk of autoimmune disease due to molecular mimicry.

PMID- 16287974
TI  - Cooperative cargo transport by several molecular motors.
AB  - The transport of cargo particles that are pulled by several molecular motors in a
      cooperative manner is studied theoretically in this article. The transport
      properties depend primarily on the maximal number N of motor molecules that may
      pull simultaneously on the cargo particle. Because each motor must unbind from
      the filament after a finite number of steps but can also rebind to it again, the
      actual number of pulling motors is not constant but varies with time between zero
      and N. An increase in the maximal number N leads to a strong increase of the
      average walking distance (or run length) of the cargo particle. If the cargo is
      pulled by up to N kinesin motors, for example, the walking distance is estimated
      to be 5(N-1)/N micrometers, which implies that seven or eight kinesin molecules
      are sufficient to attain an average walking distance in the centimeter range. If
      the cargo particle is pulled against an external load force, this force is shared
      between the motors, which provides a nontrivial motor-motor coupling and a
      generic mechanism for nonlinear force-velocity relationships. With increasing
      load force, the probability distribution of the instantaneous velocity is shifted
      toward smaller values, becomes broader, and develops several peaks. Our theory is
      consistent with available experimental data and makes quantitative predictions
      that are accessible to systematic in vitro experiments.

PMID- 16287975
TI  - Requirement for chitin biosynthesis in epithelial tube morphogenesis.
AB  - Many organs are composed of branched networks of epithelial tubes that transport
      vital fluids or gases. The proper size and shape of tubes are crucial for their
      transport function, but the molecular processes that govern tube size and shape
      are not well understood. Here we show that three genes required for tracheal tube
      morphogenesis in Drosophila melanogaster encode proteins involved in the
      synthesis and accumulation of chitin, a polymer of N-acetyl-beta-D-glucosamine
      that serves as a scaffold in the rigid extracellular matrix of insect cuticle. In
      all three mutants, developing tracheal tubes bud and extend normally, but the
      epithelial walls of the tubes do not expand uniformly, and the resultant tubes
      are grossly misshapen, with constricted and distended regions all along their
      lengths. The genes are expressed in tracheal cells during the expansion process,
      and chitin accumulates in the lumen of tubes, forming an expanding cylinder that
      we propose coordinates the behavior of the surrounding tracheal cells and
      stabilizes the expanding epithelium. These findings show that chitin regulates
      epithelial tube morphogenesis, in addition to its classical role protecting
      mature epithelia.

PMID- 16287976
TI  - MicroRNAs control translation initiation by inhibiting eukaryotic initiation
      factor 4E/cap and poly(A) tail function.
AB  - MicroRNAs (miRNAs) repress translation of target mRNAs by interaction with
      partially mismatched sequences in their 3' UTR. The mechanism by which they act
      on translation has remained largely obscure. We examined the translation of mRNAs
      containing four partially mismatched miRNA-binding sites in the 3' UTR in HeLa
      cells cotransfected with a cognate miRNA. The mRNAs were prepared by in vitro
      transcription and were engineered to employ different modes of translation
      initiation. We find that the 5' cap structure and the 3' poly(A) tail are each
      necessary but not sufficient for full miRNA-mediated repression of mRNA
      translation. Replacing the cap structure with an internal ribosome entry site
      from either the cricket paralysis virus or the encephalomyocarditis virus impairs
      miRNA-mediated repression. Collectively, these results demonstrate that miRNAs
      interfere with the initiation step of translation and implicate the cap-binding
      protein eukaryotic initiation factor 4E as a molecular target.

PMID- 16287977
TI  - Single-myosin crossbridge interactions with actin filaments regulated by troponin
      tropomyosin.
AB  - Striated muscle contraction is governed by the thin filament regulatory proteins
      troponin and tropomyosin. Here, we investigate the molecular mechanisms by which
      troponin-tropomyosin inhibits myosin's interactions with the thin filament in the
      absence of calcium by using a laser trap. The displacement events for a single
      myosin molecule interacting with a reconstituted thin filament were shorter (step
      size = 5 nm) and prolonged (69 ms) compared with actin alone (11 nm and 26 ms,
      respectively). However, these changes alone do not account for the degree of
      inhibition of thin filament movement observed in an ensemble assay. Our
      investigations of single- and multiple-myosin molecules with regulated thin
      filaments suggest the primary basis for this inhibition derives from an
      approximately 100-fold decrease in the probability of myosin attaching to actin.
      At higher myosin concentrations, short bursts of motility are observed in a laser
      trap consistent with the strong binding of a single-myosin crossbridge, resulting
      in cooperative binding of other cycling crossbridges. We confirmed this
      cooperativity in the in vitro motility assay by observing thin filament
      translocation in the absence of calcium but at low [ATP], consistent with rigor
      activation. We have developed a simple mechanistic model that reproduces and
      provides insight into both the observed single-myosin molecule and ensemble data
      in the absence of Ca(2+). These data support the hypothesis that thin filament
      inhibition in the absence of Ca(2+) is largely achieved by modulating the rate of
      attachment and/or transition from the weakly to strongly bound state.

PMID- 16287978
TI  - The genome sequence of Clostridium botulinum type C neurotoxin-converting phage
      and the molecular mechanisms of unstable lysogeny.
AB  - Botulinum neurotoxins (BoNTXs) produced by Clostridium botulinum are among the
      most poisonous substances known. Of the seven types of BoNTXs, genes for type C1
      and D toxins (BoNTX/C1 and D) are carried by bacteriophages. The gene for
      exoenzyme C3 also resides on these phages. Here, we present the complete genome
      sequence of c-st, a representative of BoNTX/C1-converting phages. The genome is a
      linear double-stranded DNA of 185,682 bp with 404-bp terminal direct repeats, the
      largest known temperate phage genome. We identified 198 potential protein-coding
      regions, including the genes for production of BoNTX/C1 and exoenzyme C3. Very
      exceptionally, as a viable bacteriophage, a number of insertion sequences were
      found on the c-st genome. By analyzing the molecular structure of the c-st genome
      in lysogens, we also found that it exists as a circular plasmid prophage. These
      features account for the unstable lysogeny of BoNTX phages, which has
      historically been called "pseudolysogeny." The PCR scanning analysis of other
      BoNTX/C1 and D phages based on the c-st sequence further revealed that BoNTX
      phages comprise a divergent phage family, probably generated by exchanging
      genomic segments among BoNTX phages and their relatives.

PMID- 16287980
TI  - SUMO modification negatively modulates the transcriptional activity of CREB
      binding protein via the recruitment of Daxx.
AB  - Small ubiquitin-like modifier (SUMO) modification is emerging as an important
      control in transcription regulation. Here, we show that CREB-binding protein
      (CBP), a versatile transcriptional coactivator for numerous transcription factors
      in response to diverse signaling events, can be modified by SUMO-1 at lysine
      residues 999, 1034, and 1057 both in vitro and in vivo. Mutation of the SUMO
      acceptor lysine residues either individually or in combination enhanced CBP
      transcriptional activity, and expression of a SUMO protease SENP2 potentiated the
      transcriptional activity of CBP wild-type but not its sumoylation mutant,
      indicating that SUMO modification negatively regulates CBP transcriptional
      activity. Furthermore, we demonstrated an interaction of SUMO-1-modified CBP with
      the transcriptional corepressor Daxx and an essential role of Daxx in mediating
      SUMO-dependent transcriptional regulation of CBP through histone deacetylase 2
      recruitment. Together, our findings indicate that SUMO modification and
      subsequent recruitment of Daxx represent a previously undescribed mechanism in
      modulating CBP transcriptional potential.

PMID- 16287979
TI  - Toll-like receptor 3 ligand attenuates LPS-induced liver injury by down
      regulation of toll-like receptor 4 expression on macrophages.
AB  - This study demonstrates that pretreatment with polyinosinic-polycytidylic acid
      (poly I:C) significantly decreased the mortality and liver injury caused by
      injection of lipopolysaccharide (LPS) in the presence of d-galactosamine (d-GalN)
      in C57BL/6 mice. Depletion of natural killer, natural killer T, and T cells did
      not change the protective effect of poly I:C on LPS/d-GalN-induced liver injury
      in vivo. However, depletion of macrophages abolished LPS/d-GalN-induced fulminant
      hepatitis, which could be restored by adoptive transfer of macrophages but not by
      transfer of poly I:C-treated macrophages. Treatment with poly I:C down-regulated
      the expression of the toll-like receptor 4 (TLR4) on macrophages and reduced the
      sensitivity of macrophages (Kupffer cells and peritoneal macrophages from C57BL/6
      mice, or RAW264.7 cells) to LPS stimulation. Poly I:C pretreatment also impaired
      the signaling of mitogen-activated protein kinases and NF-kappaB induced by LPS
      in RAW264.7 cells. Blockade of TLR3 with a TLR3 antibody abolished poly I:C down
      regulation of TLR4 expression and LPS stimulation of TNF-alpha production in
      RAW264.7 cells. Taken together, our findings suggest that activation of TLR3 by
      its ligand, poly I:C, induced LPS tolerance by down-regulation of TLR4 expression
      on macrophages.

PMID- 16287982
TI  - Development of highly ciprofloxacin-resistant laboratory mutants of Acinetobacter
      baumannii lacking topoisomerase IV gene mutations.

PMID- 16287981
TI  - Bayesian coclustering of Anopheles gene expression time series: study of immune
      defense response to multiple experimental challenges.
AB  - We present a method for Bayesian model-based hierarchical coclustering of gene
      expression data and use it to study the temporal transcription responses of an
      Anopheles gambiae cell line upon challenge with multiple microbial elicitors. The
      method fits statistical regression models to the gene expression time series for
      each experiment and performs coclustering on the genes by optimizing a joint
      probability model, characterizing gene coregulation between multiple experiments.
      We compute the model using a two-stage Expectation-Maximization-type algorithm,
      first fixing the cross-experiment covariance structure and using efficient
      Bayesian hierarchical clustering to obtain a locally optimal clustering of the
      gene expression profiles and then, conditional on that clustering, carrying out
      Bayesian inference on the cross-experiment covariance using Markov chain Monte
      Carlo simulation to obtain an expectation. For the problem of model choice, we
      use a cross-validatory approach to decide between individual experiment modeling
      and varying levels of coclustering. Our method successfully generates tightly
      coregulated clusters of genes that are implicated in related processes and
      therefore can be used for analysis of global transcript responses to various
      stimuli and prediction of gene functions.

PMID- 16287985
TI  - By invitation only.

PMID- 16287983
TI  - Staphylococcus aureus small colony variants are resistant to the antimicrobial
      peptide lactoferricin B.
AB  - OBJECTIVES: To determine whether Staphylococcus aureus small colony variants
      (SCVs) are resistant to the antimicrobial peptide lactoferricin B. To assess if
      deficiency in transmembrane potential, a common characteristic of SCVs that are
      haemin- or menadione-auxotrophs, affects the uptake of the peptide into the
      bacterial cytoplasm. METHODS: A broth microdilution technique was used for
      susceptibility testing to determine the MIC of lactoferricin B for SCVs with
      three different auxotrophisms (haemin, menadione or thymidine) and their isogenic
      parent strains. Both clinical isolates and genetically defined mutants were used.
      The internalization of lactoferricin B in a hemB mutant and the respective parent
      strain was studied using transmission electron microscopy and immunogold
      labelling. RESULTS: All SCVs showed reduced susceptibility to lactoferricin B
      irrespective of their auxotrophy compared with their isogenic parent strains. The
      MIC for all SCVs was >256 mg/L, whereas the MICs for the parent strains ranged
      from 16-256 mg/L. Surprisingly, the hemB mutant contained significantly more
      lactoferricin B intracellularly than the respective parent strain. CONCLUSIONS:
      The resistance mechanism of SCVs towards the antimicrobial peptide lactoferricin
      B is presumably caused by the metabolic changes present in SCVs rather than by a
      changed transmembrane potential of SCVs or reduced uptake of the peptide.

PMID- 16287986
TI  - Ecto-ADP-ribose transferases: cell-surface response to local tissue injury.
AB  - Ecto-ADP-ribose transferases (ecto-ARTs) catalyze the transfer of ADP-ribose from
      NAD(+) to arginine residues in cell-surface proteins. Since the concentration of
      extracellular NAD(+) is very low under normal physiological conditions but rises
      significantly upon tissue injury or membrane stress, it is postulated that the
      main role of ecto-ARTs is to ADP-ribosylate and regulate the function of certain
      membrane receptors in response to elevated levels of NAD(+).

PMID- 16287987
TI  - New insights into biliverdin reductase functions: linking heme metabolism to cell
      signaling.
AB  - Biliverdin reductase (BVR) functions in cell signaling through three distinct
      tracks: a dual-specificity kinase that functions in the insulin receptor/MAPK
      pathways (25, 29, 51); a bzip-type transcription factor for ATF-2/CREB and HO-1
      regulation (1, 25); and a reductase that catalyzes the conversion of biliverdin
      to bilirubin (27). These, together with the protein's primary and secondary
      features, intimately link BVR to the entire spectrum of cell-signaling cascades.

PMID- 16287988
TI  - Ras-related signaling pathways in valve development: ebb and flow.
AB  - Congenital heart defects affect approximately 1 in every 100 live births, and
      deficits in the formation of the mitral, tricuspid, and outflow tract valves
      account for 20-25% of all cardiac malformations. Mutations in genes that affect
      Ras signaling have been identified in individuals with congenital valve disease
      associated with Noonan syndrome and neurofibromatosis type 1. Dissection of Ras
      related signaling pathways during valvulogenesis provides seminal insight into
      cellular and molecular mechanisms that contribute to congenital heart disease.

PMID- 16287989
TI  - Ubiquitylation of ion channels.
AB  - Ubiquitylation (i.e., covalent attachment of ubiquitin moieties to proteins) of
      ion channels allows regulation of their activity and fate. Nedd4/Nedd4-like
      ubiquitin-protein ligases bind to, ubiquitylate, and modulate the internalization
      of several channels bearing PY motifs, whereas endoplasmic reticulum-associated
      degradation (involving ubiquitylation) plays an important role in the biogenesis
      of normal and defective channels.

PMID- 16287990
TI  - The KCNQ1 potassium channel: from gene to physiological function.
AB  - The voltage-gated KCNQ1 (KvLQT1, Kv7.1) potassium channel plays a crucial role in
      shaping the cardiac action potential as well as in controlling the water and salt
      homeostasis in several epithelial tissues. KCNQ1 channels in these tissues are
      tightly regulated by auxiliary proteins and accessory factors, capable of
      modulating the properties of the channel complexes. This paper reviews the
      current knowledge about the KCNQ1 channel with a major focus on interacting
      proteins and physiological functions.

PMID- 16287991
TI  - Role of acid/base transporters in the male reproductive tract and potential
      consequences of their malfunction.
AB  - Acid/base transporters play a key role in establishing an acidic luminal
      environment for sperm maturation and storage in the male reproductive tract.
      Impairment of the acidification capacity of the epididymis, via either genetic
      mutations or exposure to environmental factors, may have profound consequences on
      male fertility.

PMID- 16287992
TI  - Acid acclimation by Helicobacter pylori.
AB  - Helicobacter pylori is a Gram-negative neutralophile associated with peptic
      ulcers and gastric cancer. It has a unique ability to colonize the human stomach
      by acid acclimation. It uses the pH-gated urea channel, UreI, to enhance urea
      access to intrabacterial urease and a membrane-anchored periplasmic carbonic
      anhydrase to regulate periplasmic pH to approximately 6.1 in acidic media,
      whereas other neutralophiles cannot regulate periplasmic pH and thus only transit
      the stomach.

PMID- 16287993
TI  - Type I insulin-like growth factor receptor as a therapeutic target in cancer.
AB  - Data from experimental model systems and population studies have implicated type
      I insulin-like growth factor receptor (IGF1R) signaling in many different human
      cancers. Drugs to disrupt IGF1R function have been developed and are now entering
      clinical trial. This brief review will identify key areas to consider as these
      clinical trials move forward.

PMID- 16287994
TI  - Is mda-7/IL-24 a "magic bullet" for cancer?
AB  - The "holy grail" of cancer therapy is to identify and exploit genetic elements
      and signal transduction pathways capable of selectively destroying tumor cells
      without eliciting harmful effects in normal cells or tissues. To achieve this
      objective, subtraction hybridization was combined with a "differentiation
      therapy" model of cancer in which human melanoma cells were induced to revert to
      a more "normal" state, growth arrest irreversibly, and terminally differentiate
      by treatment with fibroblast IFN and mezerein. This strategy permitted the
      cloning of a variety of genes involved in regulating important physiologic
      processes, including cell cycle, response to cytokines and viruses, tumorigenesis
      and metastasis, cancer growth control, apoptosis, and senescence. A specific
      gene, melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24),
      displaying cancer-specific apoptosis-inducing properties isolated using this
      scheme has now come into the limelight as a new gene therapy for divergent
      cancers. Although the mechanism of cancer cell selectivity of mda-7/IL-24 remains
      to be delineated, numerous attributes enable this gene as an effective therapy
      for cancer, including an ability to discriminate between normal and cancer cells,
      induce apoptosis in diverse tumor cells, promote "bystander" antitumor effects,
      inhibit tumor growth and angiogenesis in animal models, synergize with radiation,
      and modulate immune responses. These unique features combined with successful
      transition into the clinic instill confidence that mda-7/IL-24, as a single or
      more likely as part of a combinatorial approach, may provide profound therapeutic
      benefit for cancer patients.

PMID- 16287995
TI  - HLA-G proteins in cancer: do they provide tumor cells with an escape mechanism?
AB  - Convincing clinical evidence indicates that the limited success of T-cell-based
      immunotherapy of malignant diseases is caused, at least in part, by the ability
      of malignant cells to escape from immune recognition and destruction. Among the
      multiple escape mechanisms identified, a major role is played by changes in the
      expression and/or function of HLA antigens expressed by tumor cells, because they
      may markedly affect tumor cell-host's immune system interactions. In this
      article, we review the data about the aberrant expression of the nonclassical HLA
      class I antigen HLA-G by tumor cells. Furthermore, we discuss the possible
      reasons for the conflicting information in the literature about HLA-G antigen
      expression by malignant cells. Lastly, in light of the well-documented
      immunotolerant function of HLA-G, we discuss the potential role of these antigens
      in the escape of tumor cells from immune recognition and destruction and in the
      clinical course of malignant diseases.

PMID- 16287997
TI  - Noninvasive in vivo detection of glutathione metabolism in tumors.
AB  - Magnetic resonance spectroscopic imaging has been used to follow glutathione
      metabolism and evaluate glutathione heterogeneity in intact tumor tissue. Stable
      isotope-labeled glutathione was detected in s.c. implanted fibrosarcoma tumors in
      anesthetized rats following infusion of [2-13C]glycine. Using 1H-decoupled 13C
      magnetic resonance spectroscopy, the appearance of [2-13C]glycine at 42.4 ppm and
      the subsequent incorporation of this isotope label into the glycyl residue of
      glutathione at 44.2 ppm can be detected. The identity and relative concentrations
      of labeled metabolites observed in the in vivo spectrum were confirmed in studies
      of tissue extracts. The high level of isotopic enrichment and the concentration
      of glutathione in tumor tissue allow for collection of spatially localized
      spectra using 13C chemical shift imaging methods. These data provide the first
      direct images of glutathione in intact tumor tissue and show metabolic
      heterogeneity. This method may lead to the ability to monitor changes in tumor
      tissue redox state that may ultimately affect diagnosis, monitoring, and
      treatment.

PMID- 16287996
TI  - Efficient deletion of normal Brca2-deficient intestinal epithelium by poly(ADP
      ribose) polymerase inhibition models potential prophylactic therapy.
AB  - The genes encoding the BRCA1 and BRCA2 tumor suppressors are the most commonly
      mutated in human familial breast cancers. Both have separate roles in the
      maintenance of genomic stability through involvement in homologous recombination,
      an error-free process enabling cells to repair DNA double-strand breaks. We have
      previously shown that cre-mediated conditional deletion of Brca2 within the mouse
      small intestine sensitizes the tissue to DNA damage. Eventually, the tissue
      repopulates via stem cells in which recombination at the floxed Brca2 allele has
      not taken place. In this study, we have treated Brca2-deficient small intestine
      with a potent small-molecule inhibitor of poly(ADP-ribose) polymerase 1 (PARP1),
      an enzyme predominantly involved in the recognition of DNA single-strand breaks.
      Brca2 deficiency rendered otherwise normal cells exquisitely sensitive to PARP
      inhibition, resulting in very high levels of apoptosis as early as 6 hours after
      treatment, with evidence for repopulation of the tissue at 12 hours. Furthermore,
      the intestines of animals treated with serial injections of the inhibitor
      repopulated very rapidly in comparison with those from untreated mice. Our
      results represent the first in vivo demonstration that inhibition of PARP1
      activity confers exquisite sensitivity to death in physiologically normal Brca2
      deficient cells, suggesting that such a regimen may be extremely potent
      prophylactically in women heterozygous for the BRCA2 gene, as well as against
      established tumors lacking functional BRCA2.

PMID- 16287998
TI  - Noninvasive visualization of adenovirus replication with a fluorescent reporter
      in the E3 region.
AB  - To overcome the inefficacy and undesirable side effects of current cancer
      treatment strategies, conditionally replicative adenoviruses have been developed
      to exploit the unique mechanism of oncolysis afforded by tumor-specific viral
      replication. Despite rapid translation into clinical trials and the established
      safety of oncolytic adenoviruses, the in vivo function of these agents is not
      well understood due to lack of a noninvasive detection system for adenovirus
      replication. To address this issue, we propose the expression of a reporter from
      the adenovirus E3 region as a means to monitor replication. Adenovirus
      replication reporter vectors were constructed with the enhanced green fluorescent
      protein (EGFP) gene placed in the deleted E3 region under the control of the
      adenoviral major late promoter while retaining expression of the adenovirus death
      protein to conserve the native oncolytic capability of the virus. Strong EGFP
      fluorescence was detected from these vectors in a replication-dependent manner,
      which correlated with viral DNA replication. Fluorescence imaging in vivo
      confirmed the ability to noninvasively detect fluorescent signal during
      replication, which generally corresponded with the underlying level of viral DNA
      replication. EGFP representation of viral replication was further confirmed by
      Western blot comparison with the viral DNA content in the tumors. Imaging
      reporter expression controlled by the adenoviral major late promoter provides a
      viable approach to noninvasively monitor adenovirus replication in preclinical
      studies and has the potential for human application with clinically relevant
      imaging reporters.

PMID- 16287999
TI  - Extremely low dose ionizing radiation up-regulates CXC chemokines in normal human
      fibroblasts.
AB  - Although the public today could be exposed to X-rays as high as 1 cGy due to
      diagnostic procedures, the biological effects of this low-dose range have not
      been well established. We searched through >23,000 transcripts in normal human
      fibroblasts, HFLIII, using a novel comprehensive expression analysis method. More
      than 200 genes were up-regulated transiently by 1 cGy of X-rays during the 1-hour
      period after irradiation. We determined the nucleotide sequence of 10 up
      regulated transcripts with the greatest rate of increase in the irradiated HFLIII
      cells. Three of the 10 transcripts encoded CXC chemokines (CXCL1, CXCL2, and
      CXCL6). The rest included the transcripts of other secretory products
      (secretogranin II, thrombospondin type I domain containing 2, amphiregulin, and
      interleukin-6) and unknown genes. To test the involvement of CXC chemokines in
      cells irradiated with low doses, we irradiated HFLIII cells with 1 to 20 cGy X
      rays and transferred the media from HFLIII culture to two melanoma cell lines
      characteristic of excessive numbers of the CXC chemokine-specific receptors. The
      growth of these melanoma lines were significantly stimulated by the medium from
      HFLIII irradiated at 1 to 5 cGy. Our results indicate that human cells respond to
      doses of radiation as low as 1 cGy, and mechanisms alternative to those involved
      in moderate/high-dose studies have to be considered in understanding the
      biological effects of diagnostic level radiation. In addition, our comprehensive
      approach using a novel expression profiling method is a powerful strategy to
      explore biological functions associated with very low levels of toxic agents.

PMID- 16288000
TI  - Epigenetic transdifferentiation of normal melanocytes by a metastatic melanoma
      microenvironment.
AB  - The clinical management of cutaneous melanoma would benefit significantly from a
      better understanding of the molecular changes that occur during melanocytic
      progression to a melanoma phenotype. To gain unique insights into this process,
      we developed a three-dimensional in vitro model that allows observations of
      normal human melanocytes interacting with a metastatic melanoma matrix to
      determine whether these normal cells could be reprogrammed by inductive cues in
      the tumor cell microenvironment. The results show the epigenetic
      transdifferentiation of the normal melanocytic phenotype to that of an aggressive
      melanoma-like cell with commensurate increased migratory and invasive ability
      with no detectable genomic alterations. Removal of the transdifferentiated
      melanocytes from the inductive metastatic melanoma microenvironment results in a
      reversion to their normal phenotype. However, a normal melanocyte
      microenvironment had no epigenetic influence on the phenotype of metastatic
      melanoma cells. This novel approach identifies specific genes involved in the
      transdifferentiation of melanocytes to a more aggressive phenotype, which may
      offer significant therapeutic value.

PMID- 16288002
TI  - Cyclin-dependent kinase 4 expression is essential for neu-induced breast
      tumorigenesis.
AB  - Previous work has shown that cyclin D1 expression is required for neu- and ras
      induced, but not wnt- or c-myc-induced, breast tumorigenesis in mice. Although
      cyclin D1 binds and activates cyclin-dependent kinase 4 (Cdk4), thereby mediating
      activation of a program of E2F-dependent gene expression, it has been suggested
      that the oncogenic activities of cyclin D1 are independent of Cdk4. To determine
      whether Cdk4 expression is required for breast tumorigenesis in mice, we have
      generated compound mice ectopically expressing the neu or wnt oncogenes in the
      mammary glands of wild-type and Cdk4-/- mice. Our results show that Cdk4
      expression is required for efficient neu-induced tumorigenesis but is dispensable
      for wnt-induced breast tumorigenesis. In contrast to results previously observed
      in the mammary glands of cyclin D1-/- virgin females, our results show defects in
      mammary gland development in Cdk4-/- virgin females, suggesting differences in
      compensatory mechanisms in the absence of either subunit of the cyclin D1/Cdk4
      complex. These results suggest that drugs targeted to inhibit Cdk4 activities
      could be developed to specifically treat certain breast tumors as Cdk4 is not
      essential for viability.

PMID- 16288001
TI  - Mechanisms of inactivation of the receptor tyrosine kinase EPHB2 in colorectal
      tumors.
AB  - The receptor tyrosine kinase EPHB2 has recently been shown to be a direct
      transcriptional target of TCF/beta-catenin. Premalignant lesions of the colon
      express high levels of EPHB2 but the expression of this kinase is reduced or lost
      in most colorectal carcinomas. In addition, inactivation of EPHB2 has been shown
      to accelerate tumorigenesis initiated by APC mutation in the colon and rectum. In
      this study, we investigated the molecular mechanisms responsible for the
      inactivation of EPHB2 in colorectal tumors. We show here the presence of
      mutations in repetitive sequences in exon 17 of EPHB2 in 6 of 29 adenomas with
      microsatellite instability (MSI), and 101 of 246 MSI carcinomas (21% and 41%,
      respectively). Moreover, we found EPHB2 promoter hypermethylation in 54 of the
      101 colorectal tumors studied (53%). Importantly, EPHB2 expression was restored
      after treatment of EPHB2-methylated colon cancer cells with the DNA
      methyltransferase inhibitor 5-aza-2'-deoxycytidine. In conclusion, in this study,
      we elucidate the molecular mechanisms of inactivation of EPHB2 and show for the
      first time the high incidence of frameshift mutations in MSI colorectal tumors
      and aberrant methylation of the regulatory sequences of this important tumor
      suppressor gene.

PMID- 16288003
TI  - Induction of renal tumorigenesis with elevated levels of somatic loss of
      heterozygosity in Tsc1+/- mice on a Blm-deficient background.
AB  - A Bloom's deficient mouse model (Blm(m3/m3)) has been shown to induce colorectal
      tumorigenesis when crossed with Apc+/Min mice. Here, we investigated whether the
      Blm(m3/m3) genotype could induce tumorigenesis in extracolonic tissues in
      tuberous sclerosis 1-deficient (Tsc1+/-) mice that are predisposed to renal
      cystadenomas and carcinomas. Genotyping of offspring from Tsc1+/- Blm+/m3
      intercrosses showed that a approximately 24% excess of Tsc1+/- over Tsc1+/+ mice
      died before weaning (P = 0.016), although Blm deficiency had no cumulative effect
      on Tsc1+/- survival. Tsc1+/- Blm(m3/m3) mice had significantly more macroscopic
      and microscopic renal lesions at 3 to 6 months compared with Tsc1+/- Blm+/m3 mice
      (P =0.0003 and 0.0203, respectively), and their tumors showed significantly
      increased levels of somatic loss of heterozygosity (LOH) of the wild-type Tsc1
      (Tsc1wt) allele compared with those from Tsc1+/- Blm+/+ mice (P < 0.0001). Tsc1+/
      Blm+/m3 mice did not show significantly more renal lesions compared with Tsc1+/-
      Blm+/+ animals; however, their lesions still showed significantly increased
      levels of somatic LOH of the Tsc1wt allele (P = 0.03). Ninety-five percent (19 of
      20) of lesions from Tsc1+/- Blm+/m3 mice retained the wild-type Blm (Blm(wt))
      allele, indicating that the increased somatic LOH at Tsc1 was mediated by Blm
      haploinsufficiency. Renal lesions from a Blm-deficient background stained
      positively with anti-phospho-S6 ribosomal protein (Ser240/244), suggesting that
      these lesions develop through the normal pathway of Tsc-associated tumorigenesis.
      This work shows the use of the Blm(m3/m3) mice for inducing renal tumorigenesis,
      and the high levels (approximately 87%) of LOH in the resultant tumors will help
      facilitate mapping of loci involved in tumor progression.

PMID- 16288004
TI  - Control of multidrug resistance gene mdr1 and cancer resistance to chemotherapy
      by the longevity gene sirt1.
AB  - Irreversible growth arrest (also called senescence) has emerged recently as a
      tumor suppressor mechanism and a key determinant of cancer chemotherapy outcome.
      Previous work from our laboratory suggested that the cellular ability to undergo
      or to escape senescence dictates its fate to become drug-sensitive or drug
      resistant, respectively. In the present study, we made the hypothesis that
      longevity genes, by virtue of their ability to inhibit senescence, may contribute
      to the onset of drug resistance. We report that expression of the longevity gene
      sirt1 increased both at the RNA and protein levels in all the five drug-resistant
      cell lines tested when compared with their drug-sensitive counterparts. In
      addition, biopsies from cancer patients treated with chemotherapeutic agents also
      expressed high levels of this molecule. These changes were specific for sirt1
      because the expression of other members of its family was not affected. More
      importantly, small interfering RNA-mediated down-regulation of sirt1
      significantly reversed the resistance phenotype and reduced expression of the
      multidrug resistance molecule P-glycoprotein. This was further confirmed by
      ectopic overexpression of sirt1, which induced expression of P-glycoprotein and
      rendered cells resistant to doxorubicin. Collectively, these findings uncovered a
      novel function for the longevity gene sirt1 as a potential target for diagnosis
      and/or treatment of cancer resistance to chemotherapy. They also describe a proof
      of principle that signaling pathways implicated in longevity may share
      similarities with those leading to development of drug resistance in cancer.

PMID- 16288005
TI  - Reliable high-throughput genotyping and loss-of-heterozygosity detection in
      formalin-fixed, paraffin-embedded tumors using single nucleotide polymorphism
      arrays.
AB  - Most human cancers show genetic instabilities leading to allelic imbalances,
      including loss of heterozygosity (LOH). Single nucleotide polymorphism (SNP)
      arrays can be used to detect LOH. Currently, these arrays require intact genomic
      DNA as obtained from frozen tissue; however, for most cancer cases, only low
      quality DNA from formalin-fixed, paraffin-embedded (FFPE) tissue is available. In
      this study, we tested Illumina BeadArrays to genotype FFPE tissue and detect
      LOH/allelic imbalances in matched colorectal tumor and normal tissue. Genotypes
      were compared between leukocyte and FFPE normal tissue as well as between frozen
      and FFPE tumor tissue. Identical genotypes and LOH profiles were obtained from
      normal and tumor isolates. LOH was mainly observed on chromosomes 4, 5q, 12q,
      14q, 15q, 17p, 18, and 20p, which are commonly detected regions in colorectal
      cancer. LOH profiles of the BeadArrays were compared with profiles obtained by
      Affymetrix GeneChip 10K arrays, showing identical LOH patterns. These data show
      that genome-wide genotyping of FFPE tissue with the BeadArray gives reliable
      results and is a powerful technique for LOH analysis.

PMID- 16288006
TI  - Loss of the hSNF5 gene concomitantly inactivates p21CIP/WAF1 and p16INK4a
      activity associated with replicative senescence in A204 rhabdoid tumor cells.
AB  - hSNF5, the smallest member of the SWI/SNF chromatin remodeling complex, is lost
      in most malignant rhabdoid tumors (MRT). In MRT cell lines, reexpression of hSNF5
      induces G1 cell cycle arrest, elevated p16INK4a, and activated replicative
      senescence markers, such as beta-galactosidase (beta-Gal) and plasminogen
      activator inhibitor-1. To compare the replicative senescence caused by hSNF5 in
      A204 cells to normal cellular senescence, we examined the activation of both
      p16INK4a and p21CIP/WAF1. Analogous to normal cellular senescence, both p16INK4a
      and p21CIP/WAF1 were up-regulated following hSNF5 restoration. Furthermore, we
      found that hSNF5 bound the p16INK4a and p21CIP/WAF1 promoters, suggesting that it
      directly regulates transcription of these genes. Using p16INK4a RNA interference,
      we showed its requirement for the replicative senescence caused by hSNF5 but not
      the growth arrest. Instead, p21CIP/WAF1 remained activated by hSNF5 in the
      absence of high p16INK4a expression, apparently causing the growth arrest in
      A204. Interestingly, we also found that, in the absence of p16INK4a, reexpression
      of hSNF5 also increased protein levels of a second cyclin-dependent kinase (CDK)
      inhibitor, p18INK4c. However, our data show that lack of hSNF5 does not abrogate
      cellular responsiveness to DNA damage or growth-inhibitory factors. In summary,
      our studies suggest that hSNF5 loss may influence the regulation of multiple CDK
      inhibitors involved in replicative senescence.

PMID- 16288007
TI  - Mutation of the PIK3CA gene in anaplastic thyroid cancer.
AB  - The phosphatidylinositol 3'-kinase (PI3K) pathway is frequently activated in
      thyroid carcinomas through the constitutive activation of stimulatory molecules
      (e.g., Ras) and/or the loss of expression and/or function of the inhibitory PTEN
      protein that results in Akt activation. Recently, it has been reported that
      somatic mutations within the PI3K catalytic subunit, PIK3CA, are common (25-40%)
      among colorectal, gastric, breast, ovarian cancers, and high-grade brain tumors.
      Moreover, PIK3CA mutations have a tendency to cluster within the helical (exon 9)
      and the kinase (exon 20) domains. In this study, 13 thyroid cancer cell lines, 80
      well-differentiated thyroid carcinomas of follicular (WDFC) and papillary (WDPC)
      type, and 70 anaplastic thyroid carcinomas (ATC) were investigated, by PCR-direct
      sequencing, for activating PIK3CA mutations at exons 9 and 20. Nonsynonymous
      somatic mutations were found in 16 ATC (23%), two WDFC (8%), and one WDPC (2%).
      In 18 of the 20 ATC cases showing coexisting differentiated carcinoma, mutations,
      when present, were restricted to the ATC component and located primarily within
      the kinase domain. Three cell lines of papillary and follicular lineage (K1, K2,
      and K5) were also found mutated. In addition, activation of Akt was observed in
      most of the ATC harboring PIK3CA mutations. These findings indicate that mutant
      PIK3CA is likely to function as an oncogene among ATC and less frequently well
      differentiated thyroid carcinomas. The data also argue for a role of PIK3CA
      targeting in the treatment of ATC patients.

PMID- 16288008
TI  - Expression microarray analysis and oligo array comparative genomic hybridization
      of acquired gemcitabine resistance in mouse colon reveals selection for
      chromosomal aberrations.
AB  - Gemcitabine is a commonly used therapy for many solid tumors. Acquired resistance
      to this nucleoside analogue, however, diminishes the long-term effectiveness in a
      majority of patients. To better define the molecular background of gemcitabine
      resistance, a mouse colon tumor was selected during successive rounds of
      transplantation with continued treatment of gemcitabine. Expression microarray
      analysis was applied to determine which genes are consistently and highly
      overexpressed or underexpressed in the resistant versus the nonresistant tumor.
      For the statistical interpretation of the microarray data, a parametric model was
      implemented, which returns model-based differential gene expression (log-) ratios
      and their uncertainties. This defined a set of 13 genes, putatively responsible
      for the gemcitabine resistance in solid tumors. One of these, RRM1, was
      previously identified as an important marker for gemcitabine resistance in human
      cell lines. Five of the 13 genes, including RRM1, are located within a 3 Mb
      region at chromosome 7E1 of which four are highly overexpressed, suggesting a
      chromosomal amplification. Therefore, chromosomal copy number changes were
      measured, using oligo array comparative genomic hybridization. A narrow and high
      amplification area was identified on 7E1 that encompassed all five genes. In
      addition, reduced RNA expression of two other genes at 8E1 encoding COX4I1 and
      RPL13 could be explained by a decrease in chromosomal copy number on chromosome
      8. In conclusion, the array comparative genomic hybridization biologically
      validates our statistical approach and shows that gemcitabine is capable to
      select for chromosomally aberrant tumor cells, where changed gene expression
      levels lead to drug resistance.

PMID- 16288009
TI  - Novel molecular signaling and classification of human clinically nonfunctional
      pituitary adenomas identified by gene expression profiling and proteomic
      analyses.
AB  - Pituitary adenomas comprise 10% of intracranial tumors and occur in about 20% of
      the population. They cause significant morbidity by compression of regional
      structures or the inappropriate expression of pituitary hormones. Their molecular
      pathogenesis is unclear, and the current classification of clinically
      nonfunctional tumors does not reflect any molecular distinctions between the
      subtypes. To further elucidate the molecular changes that contribute to the
      development of these tumors and reclassify them according to the molecular basis,
      we investigated 11 nonfunctional pituitary adenomas and eight normal pituitary
      glands, using 33 oligonucleotide GeneChip microarrays. We validated microarray
      results with the reverse transcription real-time quantitative PCR, using a larger
      number of nonfunctional adenomas. We also used proteomic analysis to examine
      protein expression in these nonfunctional adenomas. Microarray analysis
      identified significant increases in the expression of 115 genes and decreases in
      169 genes, whereas proteomic analysis identified 21 up-regulated and 29 down
      regulated proteins. We observed changes in expression of SFRP1, TLE2, PITX2,
      NOTCH3, and DLK1, suggesting that the developmental Wnt and Notch pathways are
      activated and important for the progression of nonfunctional pituitary adenomas.
      We further analyzed gene expression profiles of all nonfunctional pituitary
      subtypes to each other and identified genes that were affected uniquely in each
      subtype. These results show distinct gene and protein expression patterns in
      adenomas, provide new insight into the pathogenesis and molecular classification
      of nonfunctional pituitary adenomas, and suggest that therapeutic targeting of
      the Notch pathway could be effective for these tumors.

PMID- 16288010
TI  - Postreplicative joining of DNA double-strand breaks causes genomic instability in
      DNA-PKcs-deficient mouse embryonic fibroblasts.
AB  - Combined cytogenetic and biochemical approaches were used to investigate the
      contributions of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs)
      in the maintenance of genomic stability in nonirradiated and irradiated primary
      mouse embryo fibroblasts (MEF). We show that telomere dysfunction contributes
      only marginally to genomic instability associated with DNA-PKcs deficiency in the
      absence of radiation. Following exposure to ionizing radiation, DNA-PKcs-/- MEFs
      are radiosensitized mainly as a result of the associated DNA double-strand break
      (DSB) repair defect. This defect manifests as an increase in the fraction of DSB
      rejoining with slow kinetics although nearly complete rejoining is achieved
      within 48 hours. Fifty-four hours after ionizing radiation, DNA-PKcs-/- cells
      present with a high number of simple and complex chromosome rearrangements as
      well as with unrepaired chromosome breaks. Overall, induction of chromosome
      aberrations is 6-fold higher in DNA-PKcs-/- MEFs than in their wild-type
      counterparts. Spectral karyotyping-fluorescence in situ hybridization technology
      distinguishes between rearrangements formed by prereplicative and postreplicative
      DSB rejoining and identifies sister chromatid fusion as a significant source of
      genomic instability and radiation sensitivity in DNA-PKcs-/- MEFs. Because DNA
      PKcs-/- MEFs show a strong G1 checkpoint response after ionizing radiation, we
      propose that the delayed rejoining of DNA DSBs in DNA-PKcs-/- MEFs prolongs the
      mean life of broken chromosome ends and increases the probability of incorrect
      joining. The preponderance of sister chromatid fusion as a product of incorrect
      joining points to a possible defect in S-phase arrest and emphasizes proximity in
      these misrepair events.

PMID- 16288011
TI  - Methylation-associated silencing of the nuclear receptor 1I2 gene in advanced
      type neuroblastomas, identified by bacterial artificial chromosome array-based
      methylated CpG island amplification.
AB  - To identify genes whose expression patterns are altered by methylation of DNA, we
      established a method for scanning human genomes for methylated DNA sequences,
      namely bacterial artificial chromosome array-based methylated CpG island
      amplification (BAMCA). In the course of a program using BAMCA to screen
      neuroblastoma cell lines for aberrant DNA methylation compared with stage I
      primary neuroblastoma tumors, we identified CpG methylation-dependent silencing
      of the nuclear receptor 1I2 (NR1I2) gene. NR1I2 was methylated in a subset of
      neuroblastoma cell lines and also in advanced-stage primary tumors with
      amplification of MYCN. Its methylation status was inversely associated with gene
      expression. Treatment with the demethylating agent 5-aza-2'-deoxycytidine
      restored NR1I2 transcription in neuroblastoma cell lines lacking endogenous
      expression of this gene. A CpG island located around exon 3 of NR1I2 showed
      promoter activity, and its methylation status was clearly and inversely
      correlated with NR1I2 expression status. The gene product, NR1I2, has a known
      function in regulating response to xenobiotic agents but it also suppressed
      growth of neuroblastoma cells in our experiments. We identified some possible
      transcriptional targets of NR1I2 by expression array analysis. The high
      prevalence of NR1I2 silencing by methylation in aggressive neuroblastomas,
      together with the growth-suppressive activity of NR1I2, suggests that this
      molecule could serve as a diagnostic marker to predict prognosis for
      neuroblastomas.

PMID- 16288012
TI  - Heterogeneous tumor evolution initiated by loss of pRb function in a preclinical
      prostate cancer model.
AB  - Because each change in the evolution of a cancer is predicated on the effects of
      previous events, a full understanding of selective changes and their effect on
      tumor progression can only be understood in the context of appropriate initiating
      events. Here, we define the effect of pRb function inactivation in prostate
      epithelium on both the initiation of prostate cancer and the establishment of
      selective pressures that lead to diminished Pten function and tumor evolution.
      Using genetically engineered mice, we show that inactivation of the pRb family
      proteins (Rb/p107/p130) induces epithelial proliferation and apoptosis and is
      sufficient to produce prostatic intraepithelial neoplasia (PIN) lesions. Over
      time, adenocarcinomas develop in all mice with no evidence of neuroendocrine
      tumors. Apoptosis is dependent on Pten function and not p53, unlike other
      epithelial cell types tested previously. Consequently, Pten hemizygosity reduces
      apoptosis by 50%, accelerating progression to adenocarcinomas with heterogeneous
      composition. Heterogeneity is associated with concurrent Pten haploinsufficiency
      and focal selective progression to complete Pten loss, which yields distinct
      tumor properties. Given that this analysis models the apparent timing of highly
      penetrant events in human prostate cancer, observed effects may recapitulate the
      natural evolution of prostate cancer development.

PMID- 16288013
TI  - The p53 tumor suppressor network is a key responder to microenvironmental
      components of chronic inflammatory stress.
AB  - Activation of the p53 network plays a central role in the inflammatory stress
      response associated with ulcerative colitis and may modulate cancer risk in
      patients afflicted with this chronic disease. Here, we describe the gene
      expression profiles associated with four microenvironmental components of the
      inflammatory response (NO*, H2O2, DNA replication arrest, and hypoxia) that
      result in p53 stabilization and activation. Isogenic HCT116 and HCT116 TP53-/-
      colon cancer cells were exposed to the NO* donor Sper/NO, H2O2, hypoxia, or
      hydroxyurea, and their mRNA was analyzed using oligonucleotide microarrays.
      Overall, 1,396 genes changed in a p53-dependent manner (P < 0.001), with the
      majority representing a "unique" profile for each condition. Only 14 genes were
      common to all four conditions. Included were eight known p53 target genes.
      Hierarchical sample clustering distinguished early (1 and 4 hours) from late
      responses (8, 12, and 24 hours), and each treatment was differentiated from the
      others. Overall, NO* and hypoxia stimulated similar transcriptional responses.
      Gene ontology analysis revealed cell cycle as a key feature of stress responses
      and confirmed the similarity between NO* and hypoxia. Cell cycle profiles
      analyzed by flow cytometry showed that NO* and hypoxia induced quiescent S-phase
      and G2-M arrest. Using a novel bioinformatic algorithm, we identified several
      putative p53-responsive elements among the genes induced in a p53-dependent
      manner, including four [KIAA0247, FLJ12484, p53CSV (HSPC132), and CNK (PLK3)]
      common to all exposures. In summary, the inflammatory stress response is a
      complex, integrated biological network in which p53 is a key molecular node
      regulating gene expression.

PMID- 16288014
TI  - BRCA1 and c-Myc associate to transcriptionally repress psoriasin, a DNA damage
      inducible gene.
AB  - Evidence is accumulating to suggest that some of the diverse functions associated
      with BRCA1 may relate to its ability to transcriptionally regulate key downstream
      target genes. Here, we identify S100A7 (psoriasin), S100A8, and S100A9, members
      of the S100A family of calcium-binding proteins, as novel BRCA1-repressed
      targets. We show that functional BRCA1 is required for repression of these family
      members and that a BRCA1 disease-associated mutation abrogates BRCA1-mediated
      repression of psoriasin. Furthermore, we show that BRCA1 and c-Myc form a complex
      on the psoriasin promoter and that BRCA1-mediated repression of psoriasin is
      dependent on functional c-Myc. Finally, we show that psoriasin expression is
      induced by the topoisomerase IIalpha poison, etoposide, in the absence of
      functional BRCA1 and increased psoriasin expression enhances cellular sensitivity
      to this chemotherapeutic agent. Therefore, we identified a novel transcriptional
      mechanism that is likely to contribute to BRCA1-mediated resistance to etoposide.

PMID- 16288015
TI  - Some oral poliovirus vaccines were contaminated with infectious SV40 after 1961.
AB  - Some polio vaccines prepared from 1954 to 1961 were contaminated with infectious
      SV40. It has been assumed that all polio vaccines were SV40 free in the United
      States after 1961 and in other countries after 1962. Following a WHO requirement
      that was prompted by the detection of SV40 in some human tumors, we conducted a
      multilaboratory study to test for SV40 polio vaccines prepared after 1961.
      Vaccine samples from 13 countries and the WHO seed were initially tested by PCR.
      The possible presence of intact and/or infectious SV40 DNA in PCR-positive
      samples was tested by transfection and infection of permissive CV-1 cells. All
      results were verified by immunohistochemistry, cloning, and sequencing. All the
      vaccines were SV40 free, except for vaccines from a major eastern European
      manufacturer that contained infectious SV40. We determined that the procedure
      used by this manufacturer to inactivate SV40 in oral poliovirus vaccine seed
      stocks based on heat inactivation in the presence of MgCl2 did not completely
      inactivate SV40. These SV40-contaminated vaccines were produced from early 1960s
      to about 1978 and were used throughout the world. Our findings underscore the
      potential risks of using primary monkey cells for preparing poliovirus vaccines,
      because of the possible contamination with SV40 or other monkey viruses, and
      emphasize the importance of using well-characterized cell substrates that are
      free from adventitious agents. Moreover, our results indicate possible geographic
      differences in SV40 exposure and offer a possible explanation for the different
      percentage of SV40-positive tumors detected in some laboratories.

PMID- 16288016
TI  - The differential effects of mutant p53 alleles on advanced murine lung cancer.
AB  - We report a direct comparison of the differential effects of individual p53
      mutations on lung tumor growth and progression, and the creation of a murine
      model of spontaneous advanced lung adenocarcinoma that closely recapitulates
      several aspects of advanced human pulmonary adenocarcinoma. We generated compound
      conditional knock-in mice with mutations in K-ras combined with one of three p53
      alleles: a contact mutant, a structural mutant, or a null allele. p53 loss
      strongly promoted the progression of K-ras-induced lung adenocarcinomas, yielding
      a mouse model that is strikingly reminiscent of advanced human lung
      adenocarcinoma. The influence of p53 loss on malignant progression was observed
      as early as 6 weeks after tumor initiation. Furthermore, we found that the
      contact mutant p53R270H, but not the structural mutant p53R172H, acted in a
      partially dominant-negative fashion to promote K-ras-initiated lung
      adenocarcinomas. However, for both mutants, loss-of-heterozygosity occurred
      uniformly in advanced tumors, highlighting a residual tumor-suppressive function
      conferred by the remaining wild-type allele of p53. Finally, a subset of mice
      also developed sinonasal adenocarcinomas. In contrast to the lung tumors,
      expression of the point-mutant p53 alleles strongly promoted the development of
      sinonasal adenocarcinomas compared with simple loss-of-function, suggesting a
      tissue-specific gain-of-function.

PMID- 16288017
TI  - Transcription repressor activity of spleen tyrosine kinase mediates breast tumor
      suppression.
AB  - Spleen tyrosine kinase (SYK) is a candidate tumor suppressor gene in breast. Loss
      of SYK expression in breast tumors as a result of DNA hypermethylation promotes
      tumor cell proliferation and invasion and predicts shorter survival of breast
      cancer patients. We previously reported that, in addition to its well-known
      cytoplasmic localization, the full-length Syk is also present in the nucleus and
      that Syk nuclear translocation is a rate-limiting step to determine Syk tumor
      suppressor function. Here, we show that the full-length form of Syk acts as a
      transcription repressor in the cell nucleus. Ectopic expression of Syk down
      regulates the transcription of FRA1 and cyclin D1 oncogenes. This transcription
      repressing activity of Syk is associated with its binding to members of the
      histone deacetylase family. Syk interacts with transcription factor Sp1 at the
      Sp1 DNA-binding site in the FRA1 promoter to repress Sp1-activated FRA1
      transcription. Thus, breast tumorigenesis and progression resulting from the loss
      of SYK are underscored by the derepression of Sp1-mediated oncogene
      transcription.

PMID- 16288018
TI  - Enhanced DDB2 expression protects mice from carcinogenic effects of chronic UV-B
      irradiation.
AB  - UV-damaged DNA-binding protein (UV-DDB) is essential for global genome repair
      (GGR) of UV-induced cyclobutane pyrimidine dimers (CPD). Unlike human cells,
      rodent epidermal cells are deficient in GGR of CPDs and express a subunit of UV
      DDB, DDB2, at a low level. In this study, we generated mice (K14-DDB2)
      ectopically expressing mouse DDB2 at elevated levels. Enhanced expression of DDB2
      both delayed the onset of squamous cell carcinoma and decreased the number of
      tumors per mouse in chronically UV-B light-exposed hairless mice. Enhanced
      expression of DDB2 improved repair of both CPDs and pyrimidine(6-4)pyrimidone
      photoproducts (6-4PP) in dermal fibroblasts. However, GGR of CPDs in K14-DDB2
      mice did not reach the level of efficiency of human cells, suggesting that
      another repair protein may become rate limiting when DDB2 is abundantly present.
      To complement these studies, we generated mice in which the DDB2 gene was
      disrupted. DDB2-/- and DDB2+/- mice were found to be hypersensitive to UV-induced
      skin carcinogenesis. On the cellular level, we detected a delay in the repair of
      6-4PPs in DDB2-/- dermal fibroblasts. Neither the absence nor the enhanced
      expression of DDB2 affected the levels of UV-induced apoptosis in epidermal
      keratinocytes or cultured dermal fibroblasts. Our results show an important role
      for DDB2 in the protection against UV-induced cancer and indicate that this
      protection is most likely mediated by accelerating the repair of photolesions.

PMID- 16288019
TI  - Disruption of protein kinase a regulation causes immortalization and
      dysregulation of D-type cyclins.
AB  - Phosphorylation is a key event in cell cycle control, and dysregulation of this
      process is observed in many tumors, including those associated with specific
      inherited neoplasia syndromes. We have shown previously that patients with the
      autosomal dominant tumor predisposition Carney complex carry inactivating
      mutations in the PRKAR1A gene, which encodes the type 1A regulatory subunit of
      protein kinase A (PKA), the cyclic AMP-dependent protein kinase. This defect was
      associated with dysregulation of PKA signaling, and genetic analysis has
      suggested that complete loss of the gene may be required for tumorigenesis. To
      determine the mechanism by which dysregulation of PKA causes tumor formation, we
      generated in vitro primary mouse cells lacking the Prkar1a protein. We report
      that this genetic disruption of PKA regulation causes constitutive PKA activation
      and immortalization of primary mouse embryonic fibroblasts (MEFs). At the
      molecular level, knockout of Prkar1a leads to up-regulation of D-type cyclins,
      and this increase occurs independently of other pathways known to increase cyclin
      D levels. Despite the immortalized phenotype, known mediators of cellular
      senescence (e.g., p53 and p19ARF) seem to remain intact in Prkar1a-/- MEFs.
      Mechanistically, cyclin D1 mRNA levels are not altered in the knockout cells, but
      protein half-life is markedly increased. Using this model, we provide the first
      direct genetic evidence that dysregulation of PKA promotes important steps in
      tumorigenesis, and that cyclin D1 is an essential target of PKA.

PMID- 16288021
TI  - A direct test of potential roles for beta3 and beta5 integrins in growth and
      metastasis of murine mammary carcinomas.
AB  - alphavbeta3 or alphavbeta5 integrins are widely expressed on blood and
      endothelial cells. Inhibition of the functions of these integrins has been
      reported to suppress neovascularization and tumor growth, suggesting that they
      may be critical modulators of angiogenesis. However, mice lacking these integrins
      exhibit extensive angiogenesis. Tumors arising from s.c. injections of tumor
      cells into mice lacking one or both integrins show enhanced tumor growth compared
      with growth in control mice due to both increased angiogenesis and to altered
      innate immune response. Other data suggest additional roles for these integrins,
      on either platelets or the tumor cells themselves, in enhancing tumor progression
      and metastasis. Here, we investigate the involvement of beta3 and beta5 integrins
      in the development and progression of mammary carcinomas. We intercrossed mouse
      mammary tumor virus (MMTV)-c-neu transgenic mice with beta3 or beta5 or
      beta3beta5 integrin-deficient mice and observed that multiple, large mammary
      tumors developed in 100% of mice on all genetic backgrounds. A statistically
      significant earlier onset of tumor growth was observed in the MMTV-c
      neu/beta3beta5 integrin-null females compared with control mice. No major
      differences were observed in tumor size or number, vessel number or vessel
      structure and lung metastases were observed with similar frequency and size in
      all strains. MMTV-c-neu/beta3beta5 integrin-null mice had higher numbers of
      mammary acini, which may account for the earlier onset of tumors in this strain.
      These data indicate that alphavbeta3 or alphavbeta5 integrins are not essential
      for tumor growth and progression, although they might play some role in mammary
      gland development.

PMID- 16288020
TI  - Magnetic resonance imaging visualization of hyaluronidase in ovarian carcinoma.
AB  - Hyaluronan, a high molecular weight, negatively charged polysaccharide, is a
      major constituent of the extracellular matrix. High molecular weight hyaluronan
      is antiangiogenic, but its degradation by hyaluronidase generates proangiogenic
      breakdown products. Thus, by expression of hyaluronidase, cancer cells can tilt
      the angiogenic balance of their microenvironment. Indeed, hyaluronidase-mediated
      breakdown of hyaluronan correlates with aggressiveness and invasiveness of
      ovarian cancer metastasis and with tumor angiogenesis. The goal of this work was
      to develop a novel smart contrast material for detection of hyaluronidase
      activity by magnetic resonance imaging (MRI). Gadolinium
      diethylenetriaminepentaacetic acid (GdDTPA) covalently linked to hyaluronan on
      the surface of agarose beads showed attenuated relaxivity. Hyaluronidase, either
      purified from bovine testes or secreted by ES-2 and OVCAR-3 human epithelial
      ovarian carcinoma cells, activated the hyaluronan-GdDTPA-beads by rapidly
      altering the R1 and R2 relaxation rates. The change in relaxation rates was
      consistent with the different levels of biologically active hyaluronidase
      secreted by those cells. Hyaluronan-GdDTPA-beads were further used for
      demonstration of MRI detection of hyaluronidase activity in the proximity of s.c.
      ES-2 ovarian carcinoma tumors in nude mice. Thus, hyaluronan-GdDTPA-beads could
      allow noninvasive molecular imaging of hyaluronidase-mediated tilt of the
      peritumor angiogenic balance.

PMID- 16288022
TI  - CCAAT/enhancer binding protein alpha knock-in mice exhibit early liver glycogen
      storage and reduced susceptibility to hepatocellular carcinoma.
AB  - The CCAAT/enhancer binding protein alpha (C/EBPalpha) is vital for establishing
      normal hepatic energy homeostasis and moderating hepatocellular growth. CEBPA
      loss-of-function mutations identified in acute myeloid leukemia patients support
      a tumor suppressor role for C/EBPalpha. Recent work showed reductions of
      C/EBPalpha levels in human hepatocellular carcinoma with the reductions
      correlating to tumor size and progression. We investigated the potential of
      reactivating c/ebpalpha expression during hepatic carcinogenesis to prevent tumor
      cell growth. We have developed a c/ebpalpha knock-in mouse in which a single-copy
      c/ebpalpha is regulated by one allele of the alpha-fetoprotein (AFP) gene
      promoter. The knock-in mice are physically indistinguishable from wild-type (WT)
      controls. However, knock-in animals were found to deposit fetal hepatic glycogen
      earlier than WT animals. Quantitative real-time PCR confirmed early c/ebpalpha
      expression and early glycogen synthase gene activation in knock-in fetuses. We
      then used diethylnitrosamine to induce hepatocellular carcinoma in our animals.
      Diethylnitrosamine produced half the number of hepatocellular nodules in knock-in
      mice as in WT mice. Immunohistochemistry showed reduced C/EBPalpha content in WT
      nodules whereas knock-in nodules stained strongly for C/EBPalpha. The p21 protein
      was examined because it mediates a C/EBPalpha growth arrest pathway. Nuclear p21
      was absent in WT nodules whereas cytoplasmic p21 was abundant; knock-in nodules
      were positive for nuclear p21. Interestingly, only C/EBPalpha-positive nodules
      were positive for nuclear p21, suggesting that C/EBPalpha may be required to
      direct p21 to the cell nucleus to inhibit growth. Our data establish that
      controlled C/EBPalpha production can inhibit liver tumor growth in vivo.

PMID- 16288023
TI  - The role of peroxiredoxin II in radiation-resistant MCF-7 breast cancer cells.
AB  - Although several signaling pathways have been suggested to be involved in the
      cellular response to ionizing radiation, the molecular basis of tumor resistance
      to radiation remains elusive. We have developed a unique model system based upon
      the MCF-7 human breast cancer cell line that became resistant to radiation
      treatment (MCF+FIR30) after exposure to chronic ionizing radiation. By proteomics
      analysis, we found that peroxiredoxin II (PrxII), a member of a family of
      peroxidases, is up-regulated in the radiation-derived MCF+FIR3 cells but not in
      the MCF+FIS4 cells that are relatively sensitive to radiation. Both MCF+FIR3 and
      MCF+FIS4 cell lines are from MCF+FIR30 populations. Furthermore, the resistance
      to ionizing radiation can be partially reversed by silencing the expression of
      PrxII by PrxII/small interfering RNA treatment of MCF+FIR3 resistant cells,
      suggesting that PrxII is not the sole factor responsible for the resistant
      phenotype. The relevance of this mechanism was further confirmed by the increased
      radioresistance in PrxII-overexpressing MCF+FIS4 cells when compared with vector
      control cells. The up-regulation of the PrxII protein in radioresistant cancer
      cells suggested that human peroxiredoxin plays an important role in eliminating
      the generation of reactive oxygen species by ionizing radiation. The present
      finding, together with the observation that PrxII is also up-regulated in
      response to ionizing radiation in other cell systems, strengthens the hypothesis
      that the PrxII antioxidant protein is involved in the cellular response to
      ionizing radiation and functions to reduce the intracellular reactive oxygen
      species levels, resulting in increased resistance of breast cancer cells to
      ionizing radiation.

PMID- 16288024
TI  - Interleukin-8 differentially regulates migration of tumor-associated and normal
      human brain endothelial cells.
AB  - Interleukin-8 (IL-8) is a chemokine involved in angiogenesis, a process vital to
      tumor growth. Previously, we showed that endothelial cells derived from human
      tumor tissue have different functional and phenotypic properties compared with
      normal endothelial cells. This study analyzes the role of IL-8 in regulating
      angiogenesis of tumor-associated brain endothelial cells (TuBEC). Results show
      that TuBECs have a higher baseline migration rate compared with normal brain
      endothelial cells (BEC). TuBECs are unaffected when stimulated with IL-8 whereas
      BECs are activated. This lack of response of TuBECs to IL-8 is due to the
      constitutive production of IL-8. Endogenously produced IL-8 activates TuBECs in
      an autocrine manner as shown by IL-8 receptor inhibition. Blocking either CXCR1
      or CXCR2 partially reduces TuBEC migration, whereas blocking both receptors
      further reduces migration. Treatment with antibody against vascular endothelial
      growth factor (VEGF) shows that production of IL-8 by TuBECs is dependent on
      VEGF. Transforming growth factor-beta1 (TGF-beta1), shown to down-regulate IL-8
      production in BECs, does not inhibit IL-8 production in TuBECs. In summary, these
      studies show that TuBECs constitutively secrete IL-8 and autocrine activation by
      IL-8 is the result of VEGF stimulation. Furthermore, TuBECs do not respond to the
      feedback inhibition normally induced by TGF-beta1. These data emphasize the
      functional uniqueness of TuBECs. Understanding the functions and regulatory
      processes of tumor-associated endothelial cells is critical for developing
      appropriate antiangiogenic therapies.

PMID- 16288025
TI  - The inflammatory cytokine tumor necrosis factor-alpha regulates chemokine
      receptor expression on ovarian cancer cells.
AB  - Epithelial ovarian cancer cells express the chemokine receptor, CXCR4, which may
      be associated with increased survival and metastatic potential, but the
      regulation of this receptor is not understood. The inflammatory cytokine tumor
      necrosis factor-alpha (TNF-alpha) is found in ovarian cancer biopsies and is
      associated with increased tumor grade. In this report, we show that CXCR4
      expression on human epithelial ovarian cancer cells is associated with, and can
      be modulated by, TNF-alpha. Ovarian cancer cells with high endogenous expression
      of TNF-alpha expressed higher levels of CXCR4 mRNA and protein than cells with
      low TNF-alpha expression. Stimulation of ovarian cancer cell lines and primary
      epithelial cancer cells with TNF-alpha resulted in increased CXCR4 mRNA and
      protein. The TNF-alpha-stimulated increase in CXCR4 mRNA was due partly to de
      novo synthesis, and up-regulation of CXCR4 cell surface protein increased
      migration to the CXCR4 ligand CXCL12. CXCR4 mRNA and protein was down-regulated
      by anti-TNF-alpha antibody or by targeting TNF-alpha mRNA using RNAi. TNF-alpha
      stimulation activated components of the nuclear factor kappaB pathway, and
      overexpression of the inhibitor of kappaB also reduced CXCR4 expression.
      Coculture of macrophages with ovarian cancer cells also resulted in cancer cell
      up-regulation of CXCR4 mRNA in a TNF-alpha-dependent manner. Finally, there was a
      correlation between the levels of TNF-alpha and CXCR4 mRNA in clinical biopsies
      of ovarian cancer, and TNF-alpha protein was expressed in CXCR4-positive tumor
      cells. TNF-alpha is a critical mediator of tumor promotion in a number of
      experimental cancers. Our data suggest that one mechanism may be through nuclear
      factor kappaB-dependent induction of CXCR4.

PMID- 16288026
TI  - Transforming acidic coiled coil 1 promotes transformation and mammary
      tumorigenesis.
AB  - Transforming acidic coiled coil 1 (TACC1) is a putative oncogene located within a
      breast cancer amplicon found on human chromosome 8p11. Although TACC1 has been
      reported to transform fibroblasts, it is also down-regulated in a subset of
      mammary tumors treated with anthracyclin. Here, we show that ectopic TACC1
      overexpression can cooperate with Ras to induce focus formation in murine
      fibroblast cultures and prevent death caused by overexpression of Pten or a
      dominant-negative form of protein kinase B (PKB)/Akt. In transgenic mice carrying
      TACC1 under the control of the mouse mammary tumor virus promoter, TACC1
      expression reduced apoptosis during mammary gland involution, increased the
      penetrance of mammary tumors in a pten+/- background, and decreased the average
      age of mammary tumor onset in a mouse model based on a phosphatidylinositol 3'
      kinase (PI3K)-decoupled mutant of polyoma middle T. Elevated levels of both
      phospho-PKB and phospho-extracellular signal-regulated kinase were found in
      mammary tissue containing the TACC1 transgene. Thus, TACC1 positively regulates
      the Ras and PI3K pathways, promotes Ras-mediated transformation, and prevents
      apoptosis induced by PI3K pathway inhibition. TACC1 also cooperates with
      tumorigenic mutations in the PI3K pathway and thereby plays an oncogenic role in
      tumor formation in the murine mammary gland.

PMID- 16288028
TI  - SRC tyrosine kinase and multidrug resistance protein-1 inhibitions act
      independently but cooperatively to restore paclitaxel sensitivity to paclitaxel
      resistant ovarian cancer cells.
AB  - Src tyrosine kinase has been found to be overexpressed in both mouse and human
      ovarian cancer cells as well as in human primary ovarian cancers. Furthermore,
      Src inhibition sensitizes ovarian cancer cells to chemotherapeutic agents such as
      paclitaxel and cisplatin. Interestingly, Src inhibition has also been shown to
      resensitize paclitaxel-resistant cells to the cytotoxic effects of paclitaxel.
      The current study was undertaken in an effort to determine the mechanism by which
      Src resensitizes drug-resistant ovarian cancer cells. The paclitaxel-resistant
      human (CaOV3TaxR) and mouse (ID8TaxR) ovarian cancer cell lines express large
      amounts of the multidrug resistance-1 (MDR-1) protein compared with the
      paclitaxel-sensitive parent cell lines. Src inhibition had no effect on MDR-1
      protein expression. Furthermore, Src inhibition did not affect MDR-1 function as
      determined by rhodamine 123 and paclitaxel uptake or retention. Coinhibition of
      both Src and MDR-1 synergistically enhanced paclitaxel-induced cytotoxicity in
      paclitaxel-resistant ovarian cancer cell lines. Inhibition of Src enhanced
      microtubule stabilization in paclitaxel-resistant ovarian cancer cells treated
      with paclitaxel without affecting expression of beta-tubulin isotypes and
      resulted in multipolar spindle formation and apoptosis. These results show that
      Src inhibition restores paclitaxel sensitivity to paclitaxel-resistant ovarian
      cancer cells by an MDR-independent mechanism, possibly by decreasing the critical
      intracellular concentration at which paclitaxel induces tubulin stabilization and
      bundling. Src tyrosine kinase may provide a viable target for therapeutic
      intervention in drug-resistant ovarian cancer.

PMID- 16288029
TI  - Orthotopic growth of human glioma cells quantitatively and qualitatively
      influences radiation-induced changes in gene expression.
AB  - The effect of radiation on gene expression has been most frequently studied using
      tissue culture models. To determine the influence of experimental growth
      condition on radiation-induced changes in gene expression, microarray analysis
      was done on two human glioma cell lines (U87 and U251) grown in tissue culture
      and as s.c. or i.c. xenografts. Compared with tissue culture, the number of
      genes, whose expression was affected by radiation in both cell lines, was
      increased in the s.c. xenografts and further increased in the orthotopic tumors.
      Furthermore, in each growth condition, radiation modulated the expression of a
      different set of genes. In addition, whereas there were few commonly affected
      genes after irradiation of U87 and U251 in tissue culture, there were 729 common
      changes after orthotopic irradiation. These results indicate that the influence
      of the orthotopic environment on radiation-induced modulation of gene expression
      in glioma cells was both quantitative and qualitative. Moreover, they suggest
      that investigations of the functional consequence of radiation-induced gene
      expression will require accounting for experimental growth conditions.

PMID- 16288027
TI  - Simultaneous inhibition of EGFR, VEGFR, and platelet-derived growth factor
      receptor signaling combined with gemcitabine produces therapy of human pancreatic
      carcinoma and prolongs survival in an orthotopic nude mouse model.
AB  - Although gemcitabine has been approved as the first-line chemotherapeutic reagent
      for pancreatic cancer, its response rate is low and average survival duration is
      still only marginal. Because epidermal growth factor receptor (EGFR), vascular
      endothelial growth factor receptor (VEGFR), and platelet-derived growth factor
      receptor (PDGFR) modulate tumor progression, we hypothesized that inhibition of
      phosphorylation of all three on tumor cells, tumor-associated endothelial cells,
      and stroma cells would improve the treatment efficacy of gemcitabine in an
      orthotopic pancreatic tumor model in nude mice and prolong survival. We implanted
      L3.6pl, a human pancreatic cancer cell, in the pancreas of nude mice. We found
      that tumor-associated endothelial cells in this model highly expressed
      phosphorylated EGFR, VEGFR, and PDGFR. Oral administration of AEE788, a dual
      tyrosine kinase inhibitor against EGFR and VEGFR, decreased phosphorylation of
      EGFR and VEGFR. PDGFR phosphorylation was inhibited by STI571. Although i.p.
      injection of gemcitabine did not inhibit tumor growth, its combination with
      AEE788 and STI571 produced >80% inhibition of tumor growth and prolonged survival
      in parallel with increases in number of tumor cells and tumor-associated
      endothelial cell apoptosis, decreased microvascular density, decreased
      proliferation rate, and prolonged survival. STI571 treatment also decreased
      pericyte coverage on tumor-associated endothelial cells. Thus, inhibiting
      phosphorylation of EGFR, VEGFR, and PDGFR in combination with gemcitabine
      enhanced the efficacy of gemcitabine, resulting in inhibition of experimental
      human pancreatic cancer growth and significant prolongation of survival.

PMID- 16288030
TI  - Destabilization of Kruppel-like factor 4 protein in response to serum stimulation
      involves the ubiquitin-proteasome pathway.
AB  - Although the zinc finger transcription factor Kruppel-like factor 4 (KLF4) has
      been shown to be a negative regulator of cell proliferation, the mechanisms
      underlying the posttranslational modification of KLF4, especially at the level of
      protein degradation, are poorly understood. Here, we show that KLF4 protein
      levels in quiescent cells were high, but decreased rapidly as cells entered the
      proliferating stage following serum stimulation. This decrease was partially
      reversed by pretreatment with MG132, a proteasome inhibitor. Moreover, KLF4 was
      an unstable protein that underwent rapid turnover, and exhibited a relatively
      short half-life (t1/2 approximately 120 minutes). To investigate the involvement
      of the ubiquitin-proteasome pathway in the regulation of the stability of KLF4,
      HCT116 cells were treated with proteasome inhibitors. Our results showed that,
      following lactacystin treatment, levels of endogenous KLF4 increased in a time-
      and dose-dependent manners. Using a cell-free system, in vitro-translated 35S
      labeled KLF4 protein was degraded by protein extracts prepared from exponentially
      growing HCT116 cells in the presence of ATP. These effects were prevented by
      pretreatment with MG132 or replacement of ATP with ATP-gamma-S, a nonhydrolyzable
      analogue of ATP, suggesting that ATP is required for KLF4 degradation by the 26S
      proteasome. In addition, KLF4 was subject to ubiquitination when cells were
      treated with the proteasome inhibitor or transfected with exogenous ubiquitin.
      Collectively, these results indicate that destabilization of KLF4 following serum
      stimulation is mediated, at least in part, through a ubiquitin-proteasome
      pathway.

PMID- 16288031
TI  - A novel RING-type ubiquitin ligase breast cancer-associated gene 2 correlates
      with outcome in invasive breast cancer.
AB  - The RING finger family of proteins possess ubiquitin ligase activity and play
      pivotal roles in protein degradation and receptor-mediated endocytosis. In this
      study, we examined whether the breast cancer-associated gene 2 (BCA2), a novel
      RING domain protein, has E3 ubiquitin ligase activity and investigated its
      expression status in breast tumors. The full-length BCA2 gene was cloned from the
      human breast cancer cell line MDA-MB-468. It encodes an open reading frame of 304
      amino acids and contains a RING-H2 domain. BCA2 maps to chromosome 1q21.1, a
      region known to harbor cytogenetic aberrations in breast cancers. We found that
      the BCA2 protein has an intrinsic autoubiquitination activity, the hallmark of E3
      ligases, whereas mutant RING protein is not autoubiquitinated. This indicates
      that the BCA2 ubiquitin ligase activity is dependent on the RING-H2 domain. Using
      tissue microarrays and immunohistochemistry, we found strong to intermediate BCA2
      staining in 56% of 945 invasive breast cancers cases, which was significantly
      correlated with positive estrogen receptor status [odds ratio (OR), 1.51; P =
      0.004], negative lymph node status (OR, 0.73; P = 0.02), and an increase in
      disease-free survival for regional recurrence (OR, 0.45; P = 0.03).
      Overexpression of BCA2 increased proliferation and small interfering RNA
      inhibited growth of T47D human breast cancer cells and NIH3T3 mouse cells. The
      autoubiquitination activity of BCA2 indicates that it is a novel RING-type E3
      ligase. Its association with clinical measures and its effects on cell growth
      indicate that BCA2 may be important for the ubiquitin modification of proteins
      crucial to breast carcinogenesis and growth.

PMID- 16288032
TI  - MUC1 oncoprotein blocks glycogen synthase kinase 3beta-mediated phosphorylation
      and degradation of beta-catenin.
AB  - Dysregulation of beta-catenin is of importance to the development of diverse
      human malignancies. The MUC1 oncoprotein is aberrantly overexpressed by most
      human carcinomas and associates with beta-catenin. However, the functional
      significance of the MUC1-beta-catenin interaction is not known. Here, we show
      that MUC1 increases beta-catenin levels in the cytoplasm and nucleus of carcinoma
      cells. Previous studies have shown that glycogen synthase kinase 3beta (GSK3beta)
      phosphorylates beta-catenin and thereby targets it for proteosomal degradation.
      Consistent with the up-regulation of beta-catenin levels, our results show that
      MUC1 blocks GSK3beta-mediated phosphorylation and degradation of beta-catenin. To
      further define the interaction between MUC1 and beta-catenin, we identified a
      serine-rich motif (SRM) in the MUC1 cytoplasmic domain that binds directly to
      beta-catenin Armadillo repeats. Mutation of the SRM attenuated binding of MUC1 to
      beta-catenin and MUC1-mediated inhibition of beta-catenin degradation.
      Importantly, disruption of the MUC1-beta-catenin interaction with the SRM mutant
      also attenuated MUC1-induced anchorage-dependent and -independent growth and
      delayed MUC1-mediated tumorigenicity. These findings indicate that MUC1 promotes
      transformation, at least in part, by blocking GSK3beta-mediated phosphorylation
      and thereby degradation of beta-catenin.

PMID- 16288033
TI  - Identification of SFRP1 as a candidate mediator of stromal-to-epithelial
      signaling in prostate cancer.
AB  - Genetic changes in epithelial cells initiate the development of prostatic
      adenocarcinomas. As nascent tumors grow and undergo progression, epithelial tumor
      cells are intimately associated with stromal cells. Stromal cells within the
      tumor microenvironment acquire new properties, including the capacity to promote
      phenotypic and genetic progression in adjacent epithelial cells. Affymetrix
      microarrays were used to identify 119 genes differentially expressed between
      normal-derived and carcinoma-derived prostatic stromal cells. These included 31
      genes encoding extracellular proteins that may act as stromal-to-epithelial
      paracrine signals. Further investigation of one of these genes, secreted frizzled
      related protein 1 (SFRP1), revealed that its expression parallels prostatic
      growth with high expression during prostatic development, low expression in the
      adult prostate, and elevated expression in prostatic tumor stroma. In addition,
      as prostatic epithelial cells progressed to a tumorigenic state under the
      influence of tumor stroma, SFRP1 became overexpressed in the progressed
      epithelial cells. To further understand the roles of SFRP1 in the prostate, we
      tested the affects of increased SFRP1 levels on prostatic tissues and cells.
      Treatment of developing prostates with SFRP1 in culture led to increased organ
      growth. Treatment of a human prostatic epithelial cell line with SFRP1 led to
      increased proliferation, decreased apoptosis, and decreased signaling through the
      Wnt/beta-catenin pathway in vitro and increased proliferation in vivo. These data
      suggest that overexpression of SFRP1 by prostatic tumor stroma may account for
      the previously reported capacity of prostatic tumor stroma to provide a pro
      proliferative paracrine signal to adjacent epithelial cells.

PMID- 16288035
TI  - Alternative splicing of fibroblast growth factor receptor 3 produces a secreted
      isoform that inhibits fibroblast growth factor-induced proliferation and is
      repressed in urothelial carcinoma cell lines.
AB  - Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine
      kinases that play key roles in proliferation, differentiation, and tumorigenesis.
      FGFR3 was identified as the major family member expressed in both normal human
      urothelium and cultured normal human urothelial (NHU) cells and was expressed as
      the IIIb isoform. We also identified a splice variant, FGFR3 Delta8-10, lacking
      exons encoding the COOH-terminal half of immunoglobulin-like domain III and the
      transmembrane domain. Previous reports have assumed that this is a cancer
      specific splice variant. We showed that FGFR3 Delta8-10 is a normal transcript in
      NHU cells and is translated, N-glycosylated, and secreted. Primary urothelium
      expressed high levels of FGFR3 transcripts. In culture, levels were reduced in
      actively proliferating cells but increased at confluence and as cells approached
      senescence. Cells overexpressing FGFR3 IIIb showed FGF1-induced proliferation,
      which was inhibited by the addition of FGFR3 Delta8-10. In bladder tumor cell
      lines derived from aggressive carcinomas, there were significant alterations in
      the relative expression of isoforms including an overall decrease in the
      proportion of FGFR3 Delta8-10 and predominant expression of FGFR3 IIIc in some
      cases. In summary, alternative splicing of FGFR3 IIIb in NHU cells represents a
      normal mechanism to generate a transcript that regulates proliferation and in
      bladder cancer, the ratio of FGFR3 isoforms is significantly altered.

PMID- 16288034
TI  - Transforming growth factor-beta activation of phosphatidylinositol 3-kinase is
      independent of Smad2 and Smad3 and regulates fibroblast responses via p21
      activated kinase-2.
AB  - Transforming growth factor-beta (TGF-beta) stimulates cellular proliferation and
      transformation to a myofibroblast phenotype in vivo and in a subset of fibroblast
      cell lines. As the Smad pathway is activated by TGF-beta in essentially all cell
      types, it is unlikely to be the sole mediator of cell type-specific outcomes to
      TGF-beta stimulation. In the current study, we determined that TGF-beta receptor
      signaling activates phosphatidylinositol 3-kinase (PI3K) in several fibroblast
      but not epithelial cultures independently of Smad2 and Smad3. PI3K activation
      occurs in the presence of dominant-negative dynamin and is required for p21
      activated kinase-2 kinase activity and the increased proliferation and
      morphologic change induced by TGF-beta in vitro.

PMID- 16288036
TI  - Kisspeptin-10-induced signaling of GPR54 negatively regulates chemotactic
      responses mediated by CXCR4: a potential mechanism for the metastasis suppressor
      activity of kisspeptins.
AB  - The product of the KiSS-1 gene is absent or expressed at low level in metastatic
      melanoma and breast cancer compared with their nonmetastatic counterparts. A
      polypeptide derived from the KiSS-1 product, designated kisspeptin-10 (Kp-10),
      activates a receptor coupled to Galphaq subunits (GPR54 or KiSS-1R). To study the
      mechanism by which Kp-10 antagonizes metastatic spread, the effect on CXCR4
      mediated signaling, which has been shown to direct organ-specific migration of
      tumor cells, was determined. Kp-10 blocked chemotaxis of tumor cells expressing
      CXCR4 in response to low and high concentrations of SDF-1/CXCL12 and inhibited
      mobilization of calcium ions induced by this ligand. Pretreatment with Kp-10 did
      not induce down-modulation of cell surface CXCR4 expression, reduce affinity for
      SDF-1/CXCL12, or alter Galphai subunit activation stimulated by this ligand.
      Although Kp-10 stimulated prolonged phosphorylation of extracellular signal
      regulated kinase 1/2, it inhibited the phosphorylation of Akt induced by SDF-1.
      The ability of Kp-10 to inhibit signaling and chemotaxis induced by SDF-1
      indicates that activation of GPR54 signaling may negatively regulate the role of
      CXCR4 in programming tumor metastasis.

PMID- 16288037
TI  - Cancer-specific functions of SIRT1 enable human epithelial cancer cell growth and
      survival.
AB  - SIRT1 is a conserved NAD-dependent deacetylase that regulates life span in accord
      with nutritional provision. In mammalian cells, SIRT1 also down-regulates stress
      induced p53 and FoxO pathways for apoptosis, thus favoring survival under stress.
      The functioning of SIRT1 under normal, nonstressed conditions of cell growth is
      unknown. Here we have asked if SIRT1 has the capacity to influence cell viability
      in the absence of applied stress. For this purpose we used synthetic small
      interfering RNA to silence SIRT1 gene expression by RNA interference (RNAi). We
      show that the process of RNAi, by itself, does not affect cell growth and is not
      sufficient to activate a cellular stress response (indicated by lack of
      activation of endogenous p53). We also show that, in the absence of applied
      stress, SIRT1 silencing induces growth arrest and/or apoptosis in human
      epithelial cancer cells. In contrast, normal human epithelial cells and normal
      human diploid fibroblasts seem to be refractory to SIRT1 silencing. Combined gene
      knockout with RNAi cosilencing experiments indicate that SIRT1 and Bcl-2 may
      suppress separable apoptotic pathways in the same cell lineage and that the SIRT1
      regulated pathway is independent of p53, Bax, and caspase-2. Alternatively, SIRT1
      may suppress apoptosis downstream from these apoptotic factors. In either case,
      we show that FoxO4 (but not FoxO3) is required as proapoptotic mediator. We
      further identify caspase-3 and caspase-7 as downstream executioners of
      SIRT1/FoxO4-regulated apoptosis. Our work identifies SIRT1 as a novel target for
      selective killing of cancer versus noncancer epithelial cells.

PMID- 16288038
TI  - Suppression of urokinase receptor expression by thalidomide is associated with
      inhibition of nuclear factor kappaB activation and subsequently suppressed
      ovarian cancer dissemination.
AB  - Thalidomide has been used to treat a variety of diseases ranging from alleviation
      of autoimmune disorders to prevention of metastasis of cancers. It has been shown
      previously that increased levels of urokinase-type plasminogen activator receptor
      (uPAR) correlate well with higher invasive phenotype. We examined whether
      thalidomide is able to suppress the expression of uPAR mRNA and protein in human
      ovarian cancer cell line HRA and human chondrosarcoma cell line HCS-2/8. Here, we
      show that: (a) thalidomide suppresses the expression of constitutive and
      transforming growth factor-beta1 (TGF-beta1)-induced uPAR mRNA and protein; (b) a
      nuclear factor kappaB (NF-kappaB) activation system (phosphorylation of IkappaB
      alpha and degradation of IkappaB-alpha) is necessary for the TGF-beta1-induced
      increase in uPAR expression, because L-1-tosylamido-2-phenylethyl chloromethyl
      ketone, a NF-kappaB inhibitor, reduced the uPAR production as well as mRNA
      expression; (c) thalidomide failed to further strengthen L-1-tosylamido-2
      phenylethyl chloromethyl ketone's action; (d) the once-daily i.p. administration
      of thalidomide (400 microg/g body weight/d) decreased progressive growth of HRA
      tumors and ascites formation in an in vivo animal model; and (e) the once-daily
      i.p. administration of thalidomide in combination with paclitaxel (i.p., 100
      microg/20 g at days 2 and 5) significantly decreased progressive growth of HRA
      cells in a synergistic fashion. We conclude that thalidomide down-regulates
      constitutive and TGF-beta1-stimulated uPAR mRNA and protein expression possibly
      through suppression of NF-kappaB activation. Furthermore, combination therapy
      with thalidomide plus paclitaxel may be an effective way to markedly reduce i.p.
      tumor growth and ascites in ovarian cancer dissemination.

PMID- 16288039
TI  - Sensitization of human carcinoma cells to alkylating agents by small interfering
      RNA suppression of 3-alkyladenine-DNA glycosylase.
AB  - One of the major cytotoxic lesions generated by alkylating agents is DNA 3
      alkyladenine, which can be excised by 3-alkyladenine DNA glycosylase (AAG).
      Inhibition of AAG may therefore result in increased cellular sensitivity to
      chemotherapeutic alkylating agents. To investigate this possibility, we have
      examined the role of AAG in protecting human tumor cells against such agents.
      Plasmids that express small interfering RNAs targeted to two different regions of
      AAG mRNA were transfected into HeLa cervical carcinoma cells and A2780-SCA
      ovarian carcinoma cells. Stable derivatives of both cell types with low AAG
      protein levels were sensitized to alkylating agents. Two HeLa cell lines with AAG
      protein levels reduced by at least 80% to 90% displayed a 5- to 10-fold increase
      in sensitivity to methyl methanesulfonate, N-methyl-N-nitrosourea, and the
      chemotherapeutic drugs temozolomide and 1,3-bis(2-chloroethyl)-1-nitrosourea.
      These cells showed no increase in sensitivity to UV light or ionizing radiation.
      After treatment with methyl methanesulfonate, AAG knockdown HeLa cells were
      delayed in S phase but accumulated in G2-M. Our data support the hypothesis that
      ablation of AAG activity in human tumor cells may provide a useful strategy to
      enhance the efficacy of current chemotherapeutic regimens that include alkylating
      agents.

PMID- 16288040
TI  - Identification of an inactivating cysteine switch in protein kinase Cepsilon, a
      rational target for the design of protein kinase Cepsilon-inhibitory cancer
      therapeutics.
AB  - Critical roles played by some protein kinases in neoplastic transformation and
      progression provide a rationale for developing selective, small-molecule kinase
      inhibitors as antineoplastic drugs. Protein kinase Cepsilon (PKCepsilon) is a
      rational target for cancer therapy, because it is oncogenic and prometastatic in
      transgenic mouse models. PKCepsilon is activated by sn-1,2-diacylglycerol (DAG).
      Attempts to develop selective PKCepsilon inhibitors that block activation by DAG
      or compete with ATP have not yet met with success, suggesting a need for new
      strategies. We previously reported that cystamine and a metabolic cystine
      precursor inactivate PKCepsilon in cells in a thiol-reversible manner. In this
      report, we first determined that PKCepsilon became resistant to inactivation by
      disulfides when Cys452 was replaced with alanine by site-specific mutagenesis of
      human PKCepsilon or a constitutively active PKCepsilon mutant. These results
      showed that the disulfides inactivated PKCepsilon by thiol-disulfide exchange,
      either upon Cys452 S-thiolation or by rearrangement to an intra-protein
      disulfide. Mass spectrometric analysis of peptide digests of cystamine
      inactivated, carbamidomethylated PKCepsilon detected a peptide S-cysteaminylated
      at Cys452, indicating that Cys452 S-cysteaminylation is a stable modification.
      Furthermore, PKCepsilon inactivation by N-ethylmaleimide was Cys452 dependent,
      providing corroborative evidence that PKCepsilon inhibitors can be designed by
      targeting Cys452 with small molecules that stably modify the residue. Cys452 is
      an active site residue that is conserved in only 11 human protein kinase genes.
      Therefore, the PKCepsilon-inactivating Cys452 switch is a rational target for the
      design of antineoplastic drugs that selectively inhibit PKCepsilon.

PMID- 16288041
TI  - A comparative study on the protection profile of lidocaine, amifostine, and
      pilocarpin on the parotid gland during radiotherapy.
AB  - The aim of this study was to evaluate the individual and the synergetic
      radioprotective effect of lidocaine, amifostine, and pilocarpin on the parotid
      gland. Forty-nine rabbits were randomized into seven groups (n = 7)--control,
      irradiated sham-treated, irradiated/lidocaine-pretreated, irradiated/amifostine
      pretreated, irradiated/pilocarpin-pretreated, irradiated/lidocaine + pilocarpin
      pretreated, and irradiated/amifostine + pilocarpin-pretreated groups. One week
      before irradiation (15 Gy) and 72 hours as well as 1 month afterward, the parotid
      gland was investigated morphologically, sialoscintigraphically, and
      immunohistochemically with the use of tenascin-C and alpha smooth muscle actin.
      Compared with control animals, there was a significant reduction of the salivary
      ejection fraction in the irradiated untreated group 72 hours following radiation.
      Only animals pretreated with lidocaine or amifostine (alone or combined with
      pilocarpin) showed a slight nonsignificant reduction of salivary ejection
      fraction. Immunohistochemically, we observed a significant loss of alpha smooth
      muscle actin and an up-regulation of tenascin-C expression in
      irradiated/untreated glands. These changes were less evident in animals
      pretreated with lidocaine or lidocaine + pilocarpin. Amifostine and pilocarpin
      did not show any influence on tenascin-C or alpha smooth muscle actin expression.
      Ultrastructural damage was observed in irradiated untreated and pilocarpin
      pretreated glands. In contrast, lidocaine and amifostine could largely preserve
      the glandular ultrastructure. One month postradiation, all changes were
      regressive regardless of treatment protocol. Potential radioprotective agents
      show different effects on both morphology and function of the parotid gland.
      Associated immunohistochemical and ultrastructural findings could prove the
      prevailed protection profile of lidocaine. This may provide a prophylactic
      approach in the field of radioprotection of salivary glands.

PMID- 16288043
TI  - Sensitization for gamma-irradiation-induced apoptosis by second mitochondria
      derived activator of caspase.
AB  - Resistance to current treatment regimens, such as radiation therapy, remains a
      major concern in oncology and may be caused by defects in apoptosis programs.
      Because inhibitor of apoptosis proteins (IAPs), which are expressed at high
      levels in many tumors, block apoptosis at the core of the apoptotic machinery by
      inhibiting caspases, therapeutic modulation of IAPs could target a key control
      point in resistance. Here, we report for the first time that full-length or
      mature second mitochondria-derived activator of caspase (Smac), an inhibitor of
      IAPs, significantly enhanced gamma-irradiation-induced apoptosis and reduced
      clonogenic survival in neuroblastoma, glioblastoma, or pancreatic carcinoma
      cells. Notably, Smac had no effect on DNA damage/DNA repair, activation of
      nuclear factor-kappaB, up-regulation of p53 and p21 proteins, or cell cycle
      arrest following gamma-irradiation, indicating that Smac did not alter the
      initial damage and/or cellular stress response. Smac enhanced activation of
      caspase-2, caspase-3, caspase-8, and caspase-9, loss of mitochondrial membrane
      potential, and cytochrome c release on gamma-irradiation. Inhibition of caspases
      also blocked gamma-irradiation-induced mitochondrial perturbations, indicating
      that Smac facilitated caspase activation, which in turn triggered a mitochondrial
      amplification loop. Interestingly, mitochondrial perturbations were completely
      blocked by the broad-range caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp
      fluoromethylketone or the relatively selective caspase-2 inhibitor N
      benzyloxycarbonyl-Val-Asp-Val-Ala-Asp-fluoromethylketone, whereas caspase-8 or
      caspase-3 inhibitors only inhibited the increased drop of mitochondrial membrane
      potential provided by Smac, suggesting that caspase-2 was acting upstream of
      mitochondria after gamma-irradiation. In conclusion, our findings provide
      evidence that targeting IAPs (e.g., by Smac agonists) is a promising strategy to
      enhance radiosensitivity in human cancers.

PMID- 16288042
TI  - Laminin alpha5 chain metastasis- and angiogenesis-inhibiting peptide blocks
      fibroblast growth factor 2 activity by binding to the heparan sulfate chains of
      CD44.
AB  - Recently, we reported that the laminin alpha5 synthetic peptide A5G27
      (RLVSYNGIIFFLK, residues 2,892-2,904) binds to the CD44 receptor of B16-F10
      melanoma cells via the glycosaminoglycans on CD44 and inhibits tumor cell
      migration, invasion, and angiogenesis in a dominant-negative manner. Here, we
      have identified the potential mechanism of A5G27 activity using WiDr human
      colorectal carcinoma cells. WiDr cells bound to the laminin A5G27 peptide via the
      heparin-like and chondroitin sulfate B glycosaminoglycan side chains of CD44.
      Cell binding to fibroblast growth factor (FGF2) was blocked by laminin peptide
      A5G27 but not by either a scrambled version of this peptide or by another laminin
      peptide known to bind cell surface proteoglycans. FGF2 signaling involving
      tyrosine phosphorylation was also blocked by laminin peptide A5G27 but was not
      affected by peptide controls. Finally, we have shown that peptide A5G27 directly
      blocks FGF2 binding to heparin. Peptide A5G27 has sequence homology to a region
      on FGF2 that binds heparin and the FGF receptor and is important in FGF2 central
      cavity formation. We conclude that peptide A5G27 inhibits metastasis and
      angiogenesis by blocking FGF2 binding to the heparan sulfate side chains of CD44
      variant 3, thus decreasing FGF2 bioactivity.

PMID- 16288044
TI  - Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in
      polyubiquitination of tumor suppressor Wwox.
AB  - Aberrant activation of tyrosine kinases is linked causally to human cancers.
      Activated Cdc42-associated kinase (Ack1), an intracellular tyrosine kinase, has
      primarily been studied for its signaling properties but has not been linked to
      specific pathologic conditions. Herein, we report that expression of activated
      Ack1 in LNCaP cells, while minimally increasing growth in culture, enhanced
      anchorage-independent growth in vitro and dramatically accelerated tumorigenesis
      in nude mice. Molecular chaperone heat shock protein 90beta (Hsp90beta)-bound
      Ack1 and treatment of cells with geldanamycin, a Hsp90 inhibitor, inhibited Ack1
      kinase activity and suppressed tumorigenesis. Further, we identify the tumor
      suppressor WW domain containing oxidoreductase (Wwox) as an Ack1-interacting
      protein. Activated Ack1 tyrosine phosphorylated Wwox, leading to rapid
      dissociation of the Ack1-Wwox complex and concomitant Wwox polyubiquitination
      followed by degradation. Tyrosine phosphorylation of Wwox was critical for its
      degradation, as splice variant WwoxDelta5-8 that was not phosphorylated by Ack1
      failed to undergo polyubiquitination and degradation. It has been reported that
      phosphorylation of Wwox at Tyr33 stimulated its proapoptotic activity. We
      observed that Y33F Wwox mutant was still tyrosine phosphorylated and
      polyubiquitinated by Ack1 action. Site-directed mutagenesis revealed that
      activated Ack1 primarily phosphorylated Wwox at Tyr287, suggesting that
      phosphorylation of distinct tyrosine residues activate or degrade Wwox. Primary
      androgen-independent prostate tumors but not benign prostate showed increased
      tyrosine-phosphorylated Ack1 and decreased Wwox. Taken together, these data
      indicate that Ack1 stimulated prostate tumorigenesis in part by negatively
      regulating the proapoptotic tumor suppressor, Wwox. Further, these findings
      suggest that Ack1 could be a novel therapeutic target for prostate cancer.

PMID- 16288045
TI  - Uncoupling between epidermal growth factor receptor and downstream signals
      defines resistance to the antiproliferative effect of Gefitinib in bladder cancer
      cells.
AB  - Activation of the epidermal growth factor receptor (EGFR) and downstream
      signaling pathways, such as phosphatidylinositol-3 kinase/Akt and Ras/mitogen
      activated protein kinase (MAPK), have been implicated in causing resistance to
      EGFR-targeted therapy in solid tumors, including the urogenital tumors. To
      investigate the mechanism of resistance to EGFR inhibition in bladder cancer, we
      compared EGFR tyrosine kinase inhibitor (Gefitinib, Iressa, ZD1839) with respect
      to its inhibitory effects on three kinases situated downstream of EGFR: MAPK,
      Akt, and glycogen synthase kinase-3beta (GSK-3beta). We found that the resistance
      to the antiproliferative effects of gefitinib, in vitro as well as in vivo in
      nude mice models, was associated with uncoupling between EGFR and MAPK
      inhibition, and that GSK-3beta activation and degradation of its target cyclin D1
      were indicators of a high cell sensitivity to gefitinib. Further analysis of one
      phenotypic sensitive (253J B-V) and resistant (UM-UC13) cell lines revealed that
      platelet-derived growth factor receptor-beta (PDGFRbeta) activation was
      responsible for short circuiting the EGFR/MAPK pathway for mitogenic stimuli.
      However, invasion as well as actin dynamics were efficiently reduced by EGFR
      inhibition in UM-UC13. Chemical disruption of signaling pathways or of PDGFR
      kinase activity significantly reduced the inactive pool of cellular GSK-3beta in
      UM-UC13 cells. In conclusion, our data show that the uncoupling of EGFR with
      mitogenic pathways can cause resistance to EGFR inhibition in bladder cancer.
      Although this uncoupling may arise through different mechanisms, we suggest that
      the resistance of bladder cancer cells to EGFR blockade can be predicted early in
      the course of treatment by measuring the activation of GSK-3beta and of nuclear
      cyclin D1.

PMID- 16288046
TI  - Abrogation of heat shock protein 70 induction as a strategy to increase
      antileukemia activity of heat shock protein 90 inhibitor 17-allylamino-demethoxy
      geldanamycin.
AB  - 17-Allylamino-demethoxy geldanamycin (17-AAG) inhibits the chaperone association
      of heat shock protein 90 (hsp90) with the heat shock factor-1 (HSF-1), which
      induces the mRNA and protein levels of hsp70. Increased hsp70 levels inhibit
      death receptor and mitochondria-initiated signaling for apoptosis. Here, we show
      that ectopic overexpression of hsp70 in human acute myelogenous leukemia HL-60
      cells (HL-60/hsp70) and high endogenous hsp70 levels in Bcr-Abl-expressing
      cultured CML-BC K562 cells confers resistance to 17-AAG-induced apoptosis. In HL
      60/hsp70 cells, hsp70 was bound to Bax, inhibited 17-AAG-mediated Bax
      conformation change and mitochondrial localization, thereby inhibiting the
      mitochondria-initiated events of apoptosis. Treatment with 17-AAG attenuated the
      levels of phospho-AKT, AKT, and c-Raf but increased hsp70 levels to a similar
      extent in the control HL-60/Neo and HL-60/hsp70 cells. Pretreatment with 17-AAG,
      which induced hsp70, inhibited 1-beta-D-arabinofuranosylcytosine or etoposide
      induced apoptosis in HL-60 cells. Stable transfection of a small interfering RNA
      (siRNA) to hsp70 completely abrogated the endogenous levels of hsp70 and blocked
      17-AAG-mediated hsp70 induction, resulting in sensitizing K562/siRNA-hsp70 cells
      to 17-AAG-induced apoptosis. This was associated with decreased binding of Bax to
      hsp70 and increased 17-AAG-induced Bax conformation change. 17-AAG-mediated
      decline in the levels of AKT, c-Raf, and Bcr-Abl was similar in K562 and
      K562/siRNA-hsp70 cells. Cotreatment with KNK437, a benzylidine lactam inhibitor
      of hsp70 induction and thermotolerance, attenuated 17-AAG-mediated hsp70
      induction and increased 17-AAG-induced apoptosis and loss of clonogenic survival
      of HL-60 cells. Collectively, these data indicate that induction of hsp70
      attenuates the apoptotic effects of 17-AAG, and abrogation of hsp70 induction
      significantly enhances the antileukemia activity of 17-AAG.

PMID- 16288047
TI  - Activation of glycogen synthase kinase 3beta disrupts the binding of hexokinase
      II to mitochondria by phosphorylating voltage-dependent anion channel and
      potentiates chemotherapy-induced cytotoxicity.
AB  - Transformed cells are highly glycolytic and overexpress hexokinase II (HXK II).
      HXK II is capable of binding to the mitochondria through an interaction with the
      voltage-dependent anion channel (VDAC), an abundant outer mitochondrial membrane
      protein. The binding of HXK II to mitochondria has been shown to protect against
      loss of cell viability. Akt activation inhibits apoptosis partly by promoting the
      binding of HXK II to the mitochondria, but the mechanism through which Akt
      accomplishes this has not been characterized. The present report shows that Akt
      mediates the binding of HXK II to the mitochondria by negatively regulating the
      activity of glycogen synthase kinase 3beta (GSK3beta). On inhibition of Akt,
      GSK3beta is activated and phosphorylates VDAC. HXK II is unable to bind VDAC
      phosphorylated by GSK3beta and dissociates from the mitochondria. Inhibition of
      Akt potentiates chemotherapy-induced cytotoxicity, an effect that is dependent on
      GSK3beta activation and its attendant ability to disrupt the binding of HXK II to
      the mitochondria. Moreover, agents that can force the detachment of HXK II from
      mitochondria in the absence of Akt inhibition or GSK3beta activation promoted a
      synergistic increase in cell killing when used in conjunction with
      chemotherapeutic drugs. Such findings indicate that interference with the binding
      of HXK II to mitochondria may be a practicable modality by which to potentiate
      the efficacy of conventional chemotherapeutic agents.

PMID- 16288048
TI  - Effective treatment of preexisting melanoma with whole cell vaccines expressing
      alpha(1,3)-galactosyl epitopes.
AB  - The hyperacute immune response in humans is a potent mechanism of xenograft
      rejection mediated by complement-fixing natural antibodies recognizing alpha(1,3)
      galactosyl epitopes (alphaGal) not present on human cells. We exploited this
      immune mechanism to create a whole cell cancer vaccine to treat melanoma tumors.
      B16 melanoma vaccines genetically engineered to express alphaGal epitopes
      (B16alphaGal) effectively treated preexisting s.c. and pulmonary alphaGal
      negative melanoma (B16Null) tumors in the alpha(1,3)-galactosyltransferase
      knockout mouse model. T cells from mice vaccinated with B16alphaGal recognized
      B16Null melanoma cells measured by detection of intracellular tumor necrosis
      factor-alpha. We showed successful adoptive transfer of immunity to recipient
      mice bearing lung melanoma metastasis. Mice receiving lymphocytes from donors
      previously immunized with B16alphaGal had reduced pulmonary metastases. The
      transfer of lymphocytes from mice vaccinated with control vaccine had no effect
      in the pulmonary metastasis burden. This study unequivocally establishes for the
      first time efficacy in the treatment of preexisting melanoma tumors using whole
      cell vaccines expressing alphaGal epitopes. Vaccination with B16alphagal induced
      strong long-lasting cell-mediated antitumor immunity extended to B16Null. These
      data formed the basis for the testing of this therapeutic strategy in human
      clinical trials currently under way.

PMID- 16288049
TI  - Complement-mediated mechanisms in anti-GD2 monoclonal antibody therapy of murine
      metastatic cancer.
AB  - The role of complement in antibody therapy of cancer is in general poorly
      understood. We used the EL4 syngeneic mouse model of metastatic lymphoma to
      investigate the role of complement in immunotherapy directed against GD2, a
      target of clinical relevance. IgG2a and IgM anti-GD2 therapy protected EL4
      challenged mice from metastases and prolonged survival. Expression of CD59, an
      inhibitor of direct complement-mediated cytotoxicity (CMC), effectively protected
      EL4 cells from CMC in vitro but did not affect the outcome of monoclonal antibody
      therapy. Protection by IgG therapy was also unaffected in mice deficient in C3 or
      complement receptor 3 (CR3) but was almost completely abrogated in FcgammaR I/III
      deficient mice. These data indicate a crucial role for antibody-dependent cell
      mediated cytoxicity (ADCC). However, at lower doses of IgG, therapeutic effect
      was partially abrogated in C3-deficient mice, indicating complement-mediated
      enhancement of ADCC at limiting IgG concentration. In contrast to IgG, the
      therapeutic effect of IgM was completely abrogated in C3-deficient mice. High
      level expression of CD59 on EL4 did not influence IgM therapy, suggesting IgM
      functions by complement-dependent cell-mediated cytotoxicity (CDCC), a mechanism
      thought to be inactive against tumor cells. Thus, IgG and IgM can operate via
      different primary mechanisms of action, and CDCC and complement-dependent
      enhancement of ADCC mechanisms are operative in vivo. The effects of complement
      can be supplemental to other antibody-mediated mechanisms and likely have
      increased significance at limiting antibody concentration or low antigen density.

PMID- 16288050
TI  - Interleukin-7-dependent expansion and persistence of melanoma-specific T cells in
      lymphodepleted mice lead to tumor regression and editing.
AB  - Active-specific immunotherapy with dendritic cells loaded with peptide derived
      from the melanoma antigen, gp100, failed to mediate regression of established
      B16F10 melanoma in normal mice. Dendritic cell vaccination induced activation and
      subsequent deletion of adoptively transferred naive CD8+ T-cell receptor
      transgenic (pmel-1) T cells specific for gp100 in normal mice. In lymphodepleted
      mice, dendritic cell vaccination produced greater T-cell expansion, long-term
      persistence of memory T cells, and tumor regression. Most tumors that persisted
      in the presence of functional memory T cells had either lost or exhibited reduced
      expression of MHC class I or gp100 proteins. In contrast to other naive T cells,
      pmel-1 T cells adoptively transferred to lymphodepleted mice exhibited faster
      proliferation and a more differentiated phenotype after exposure to peptide
      pulsed dendritic cells. Proliferation and persistence of pmel-1 T cells was
      highly dependent on interleukin-7 (IL-7) in irradiated mice, and IL-15 when IL-7
      was neutralized, two critical homeostatic cytokines produced in response to the
      irradiation-induced lymphodepletion.

PMID- 16288052
TI  - Steroid receptor regulation of epidermal growth factor signaling through Src in
      breast and prostate cancer cells: steroid antagonist action.
AB  - Under conditions of short-term hormone deprivation, epidermal growth factor (EGF)
      induces DNA synthesis, cytoskeletal changes, and Src activation in MCF-7 and
      LNCaP cells. These effects are drastically inhibited by pure estradiol or
      androgen antagonists, implicating a role of the steroid receptors in these
      findings. Interestingly, EGF triggers rapid association of Src with androgen
      receptor (AR) and estradiol receptor alpha (ERalpha) in MCF-7 cells or ERbeta in
      LNCaP cells. Here, we show that, through EGF receptor (EGFR) and erb-B2, EGF
      induces tyrosine phosphorylation of ER preassociated with AR, thereby triggering
      the assembly of ER/AR with Src and EGFR. Remarkably, experiments in Cos cells
      show that this complex stimulates EGF-triggered EGFR tyrosine phosphorylation. In
      turn, estradiol and androgen antagonists, through the Src-associated receptors,
      prevent Src activation by EGF and heavily reduce EGFR tyrosine phosphorylation
      and the subsequent multiple effects, including DNA synthesis and cytoskeletal
      changes in MCF-7 cells. In addition, knockdown of ERalpha or AR gene by small
      interfering RNA (siRNA) almost abolishes EGFR tyrosine phosphorylation and DNA
      synthesis in EGF-treated MCF-7 cells. The present findings reveal that steroid
      receptors have a key role in EGF signaling. EGFR tyrosine phosphorylation,
      depending on Src, is a part of this mechanism. Understanding of EGF-triggered
      growth and invasiveness of mammary and prostate cancer cells expressing steroid
      receptors is enhanced by this report, which reveals novel aspects of steroid
      receptor action.

PMID- 16288051
TI  - Diminished expression of transcription factors nuclear factor kappaB and
      CCAAT/enhancer binding protein underlies a novel tumor evasion mechanism
      affecting macrophages of mammary tumor-bearing mice.
AB  - Interactions between malignant tumors and the host immune system shape the course
      of cancer progression. The molecular basis of such interactions is the subject of
      immense interest. Proinflammatory cytokines produced by macrophages are critical
      mediators of immune responses that contribute to the control of the advancement
      of neoplasia. We have shown that the expressions of interleukin 12 (IL-12) and
      inducible nitric oxide synthase (iNOS) are decreased in macrophages from mammary
      tumor-bearing mice. In this study, we investigated the causes of IL-12
      dysregulation and found deficient nuclear factor kappaB (NFkappaB) and
      CCAAT/enhancer binding protein (C/EBP) expression and function in tumor bearers'
      peritoneal macrophages. The constitutive expressions of NFkappaB p50, c-rel, p65,
      and C/EBPalpha and beta, as well as the lipopolysaccharide-induced nuclear
      translocation and DNA binding of NFkappaB components and C/EBPalpha and beta, are
      profoundly impaired in macrophages from mice bearing D1-DMBA-3 tumors. Because
      similar findings occur with the iNOS gene, it seems that it represents a novel
      mechanism by which tumor-derived factors interfere with the host immune defenses.

PMID- 16288053
TI  - Negative regulation of estrogen receptor alpha transactivation functions by LIM
      domain only 4 protein.
AB  - LIM domain only 4 (LMO4), a member of the LIM-only family of transcriptional
      coregulatory proteins, consists of two LIM protein-protein interaction domains
      that enable it to function as a linker protein in multiprotein complexes. Here,
      we have identified estrogen receptor alpha (ERalpha) and its corepressor,
      metastasis tumor antigen 1 (MTA1), as two novel binding partners of LMO4.
      Interestingly, LMO4 exhibited binding with both ERalpha and MTA1 and existed as a
      complex with ERalpha, MTA1, and histone deacetylases (HDAC), implying that LMO4
      was a component of the MTA1 corepressor complex. Consistent with this notion,
      LMO4 overexpression repressed ERalpha transactivation functions in an HDAC
      dependent manner. Accordingly, silencing of endogenous LMO4 expression resulted
      in a significant increased recruitment of ERalpha to target gene chromatin,
      stimulation of ERalpha transactivation activity, and enhanced expression of
      ERalpha-regulated genes. These findings suggested that LMO4 was an integral part
      of the molecular machinery involved in the negative regulation of ERalpha
      transactivation function in breast cells. Because LMO4 is up-regulated in human
      breast cancers, repression of ERalpha transactivation functions by LMO4 might
      contribute to the process of breast cancer progression by allowing the
      development of ERalpha-negative phenotypes, leading to increased aggressiveness
      of breast cancer cells.

PMID- 16288054
TI  - Expression profiling of serous low malignant potential, low-grade, and high-grade
      tumors of the ovary.
AB  - Papillary serous low malignant potential (LMP) tumors are characterized by
      malignant features and metastatic potential yet display a benign clinical course.
      The role of LMP tumors in the development of invasive epithelial cancer of the
      ovary is not clearly defined. The aim of this study is to determine the
      relationships among LMP tumors and invasive ovarian cancers and identify genes
      contributing to their phenotypes. Affymetrix U133 Plus 2.0 microarrays (Santa
      Clara, CA) were used to interrogate 80 microdissected serous LMP tumors and
      invasive ovarian malignancies along with 10 ovarian surface epithelium (OSE)
      brushings. Gene expression profiles for each tumor class were used to complete
      unsupervised hierarchical clustering analyses and identify differentially
      expressed genes contributing to these associations. Unsupervised hierarchical
      clustering analysis revealed a distinct separation between clusters containing
      borderline and high-grade lesions. The majority of low-grade tumors clustered
      with LMP tumors. Comparing OSE with high-grade and LMP expression profiles
      revealed enhanced expression of genes linked to cell proliferation, chromosomal
      instability, and epigenetic silencing in high-grade cancers, whereas LMP tumors
      displayed activated p53 signaling. The expression profiles of LMP, low-grade, and
      high-grade papillary serous ovarian carcinomas suggest that LMP tumors are
      distinct from high-grade cancers; however, they are remarkably similar to low
      grade cancers. Prominent expression of p53 pathway members may play an important
      role in the LMP tumor phenotype.

PMID- 16288055
TI  - Possible detection of pancreatic cancer by plasma protein profiling.
AB  - The survival rate of pancreatic cancer patients is the lowest among those with
      common solid tumors, and early detection is one of the most feasible means of
      improving outcomes. We compared plasma proteomes between pancreatic cancer
      patients and sex- and age-matched healthy controls using surface-enhanced laser
      desorption/ionization coupled with hybrid quadrupole time-of-flight mass
      spectrometry. Proteomic spectra were generated from a total of 245 plasma samples
      obtained from two institutes. A discriminating proteomic pattern was extracted
      from a training cohort (71 pancreatic cancer patients and 71 healthy controls)
      using a support vector machine learning algorithm and was applied to two
      validation cohorts. We recognized a set of four mass peaks at 8,766, 17,272,
      28,080, and 14,779 m/z, whose mean intensities differed significantly (Mann
      Whitney U test, P < 0.01), as most accurately discriminating cancer patients from
      healthy controls in the training cohort [sensitivity of 97.2% (69 of 71),
      specificity of 94.4% (67 of 71), and area under the curve value of 0.978]. This
      set discriminated cancer patients in the first validation cohort with a
      sensitivity of 90.9% (30 of 33) and a specificity of 91.1% (41 of 45), and its
      discriminating capacity was further validated in an independent cohort at a
      second institution. When combined with CA19-9, 100% (29 of 29 patients) of
      pancreatic cancers, including early-stage (stages I and II) tumors, were
      detected. Although a multi-institutional large-scale study will be necessary to
      confirm clinical significance, the biomarker set identified in this study may be
      applicable to using plasma samples to diagnose pancreatic cancer.

PMID- 16288056
TI  - Inhibition of intestinal tumorigenesis in Apcmin/+ mice by (-)-epigallocatechin-3
      gallate, the major catechin in green tea.
AB  - The present study was designed to investigate the effects of two main
      constituents of green tea, (-)-epigallocatechin-3-gallate (EGCG) and caffeine, on
      intestinal tumorigenesis in Apc(min/+) mice, a recognized mouse model for human
      intestinal cancer, and to elucidate possible mechanisms involved in the
      inhibitory action of the active constituent. We found that p.o. administration of
      EGCG at doses of 0.08% or 0.16% in drinking fluid significantly decreased small
      intestinal tumor formation by 37% or 47%, respectively, whereas caffeine at a
      dose of 0.044% in drinking fluid had no inhibitory activity against intestinal
      tumorigenesis. In another experiment, small intestinal tumorigenesis was
      inhibited in a dose-dependent manner by p.o. administration of EGCG in a dose
      range of 0.02% to 0.32%. P.o. administration of EGCG resulted in increased levels
      of E-cadherin and decreased levels of nuclear beta-catenin, c-Myc, phospho-Akt,
      and phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) in small
      intestinal tumors. Treatment of HT29 human colon cancer cells with EGCG (12.5 or
      20 micromol/L at different times) also increased protein levels of E-cadherin by
      27% to 58%, induced the translocation of beta-catenin from nucleus to cytoplasm
      and plasma membrane, and decreased c-Myc and cyclin D1 (20 micromol/L EGCG for 24
      hours). These results indicate that EGCG effectively inhibited intestinal
      tumorigenesis in Apc(min/+) mice, possibly through the attenuation of the
      carcinogenic events, which include aberrant nuclear beta-catenin and activated
      Akt and ERK signaling.

PMID- 16288057
TI  - DNA double strand breaks do not play a role in heat-induced cell killing.

PMID- 16288058
TI  - Minimal region of deletion on chromosomal arm 3p25.1-p25.2 in uveal melanoma.

PMID- 16288059
TI  - Comment: supratherapeutic response to ezetimibe administered with cyclosporine.

PMID- 16288063
TI  - HHS-CDC NEWS: trends in cholesterol screening and awareness of high blood
      cholesterol--US, 1991-2003.

PMID- 16288061
TI  - Comment: death of twins after intravenous varicella zoster immunoglobulin.

PMID- 16288064
TI  - Rifampin reduces the analgesic effect of transdermal fentanyl.

PMID- 16288065
TI  - HHS-CDC NEWS: influenza vaccination levels among persons aged > or =65 years and
      among persons aged 18-64 years with high-risk conditions--US, 2003.

PMID- 16288066
TI  - Vision of life: a lesson learned from a 98-year-old artist on World AIDS Day.
AB  - A large percentage of HIV-infected pregnant women referred to our HIV Pregnancy
      Program are economically disadvantaged and underserved. Many of these women
      experience additional psychosocial stressors that include domestic violence,
      depression, substance abuse, and pregnancy-related dilemmas. The major challenge
      we face at the clinic is to provide appropriate interventions in a timely manner
      to minimize perinatal HIV-1 transmission and optimize maternal and fetal well
      being. The medical urgency to ensure optimal patient care has led me to become
      more detached from our patients. The "humanistic" approach to patient care was an
      important lesson that I recently re-learned from a 98-year-old artist on World
      AIDS Day.

PMID- 16288067
TI  - Update in handheld electronic resources for evidence-based practice in the
      community setting.
AB  - OBJECTIVE: To provide an update on the handheld electronic resources for evidence
      based practice (EBP) in the community setting. DATA SOURCES: Electronic resources
      for EBP in the community setting were identified by compiling the commonly used,
      well-established resources and by searching MEDLINE and other Internet sites.
      Search terms included evidence-based medicine, evidence-based practice,
      resources, and abstraction. Only sources available for personal digital
      assistants were included. DATA EXTRACTION: Three databases were identified that
      provided abstraction and evaluation of the medical literature for the handheld
      platform. Content, features, ease of use, system requirements, and costs of each
      resource were evaluated. DATA SYNTHESIS: FIRSTConsult, InfoRetriever, and
      UpToDate were evaluated, and the utility of each in the community pharmacy
      setting was evaluated by tracking a clinically relevant example through each
      system. FIRSTConsult provides evidence-based information organized by diagnosis
      but is not searchable on the handheld platform. InfoRetriever focuses on
      searchable evidence-based summaries, while UpToDate includes comprehensive topic
      reviews. The latter 2 platforms have large system memory requirements. All 3
      sources provide evidence-based abstraction of the medical literature for the PDA
      platform, convenient for use at the point of care in community pharmacy.
      CONCLUSIONS: While users may select a particular resource based on unique
      features, each provides evidence-based abstraction of the medical literature that
      is a practical approach to EBP in the community pharmacy setting.

PMID- 16288068
TI  - Acute hypersensitivity reaction to ferric gluconate in a premedicated patient.
AB  - OBJECTIVE: To report a case of an acute hypersensitivity reaction to ferric
      gluconate in a patient premedicated with dexamethasone, diphenhydramine, and
      prochlorperazine. CASE SUMMARY: A 38-year-old female with persistent iron
      deficiency anemia was initiated on parenteral iron therapy with ferric gluconate
      125 mg intravenously over 10 minutes. The patient initially tolerated this first
      dose well; however, she later experienced nausea, dizziness, and minor tongue
      swelling. On her second course of therapy, the woman was premedicated with
      dexamethasone, diphenhydramine, and prochlorperazine prior to the same dose of
      ferric gluconate infused over 30 minutes. Subsequently, the patient developed
      epigastric pain, nausea, swelling of her lips and tongue, and hypotension. The
      symptoms abated after administration of diphenhydramine, dexamethasone, morphine,
      cimetidine, intravenous fluids, and oxygen. She was discharged after a short stay
      in the emergency department observation unit. DISCUSSION: Data are limited on the
      relative safety of ferric gluconate compared with iron dextran. Ferric gluconate
      does not appear to be associated with severe life-threatening events; however,
      the possibility of an acute hypersensitivity reaction with this product does
      exist. In this case, use of the Naranjo probability scale indicated a probable
      relationship between the hypersensitivity reaction and ferric gluconate.
      CONCLUSIONS: Healthcare professionals should be aware of this serious but rare
      event and encouraged to further document and report these events.

PMID- 16288069
TI  - Penicillin-induced Jarisch-Herxheimer reaction.
AB  - OBJECTIVE: To report a case of Jarisch-Herxheimer reaction (JHR) in a patient
      with presumed neurosyphilis and HIV. CASE SUMMARY: A 45-year-old HIV-positive man
      (CD4+ count 450 cells/mm(3) and history of AIDS-defining illness) presented with
      JHR after an initial intravenous dose of penicillin G for presumed neurosyphilis.
      The patient described feeling cold with worsening headache and chills
      approximately one hour after infusion of the first dose of penicillin. On
      examination, rigors, shallow inspirations, and chills were noted. He was
      afebrile, tachycardic, and tachypneic and had an oxygen saturation of 94% while
      breathing room air. His symptoms resolved within 10 minutes. Initially, this
      reaction was thought to be a result of a drug allergy, but upon further review,
      we determined that it was JHR. DISCUSSION: It is not uncommon to confuse drug
      allergy with JHR. An objective causality assessment suggests that the JHR in our
      patient was probably related to penicillin. JHR is a self-limiting condition that
      warrants the continuation of antibiotic treatment in syphilis patients.
      CONCLUSIONS: JHR should be an anticipated reaction to early doses of antibiotic
      treatment for treponemal diseases, such as syphilis. Treatment of JHR is largely
      supportive, such as administering antipyretic and antiinflammatory agents.
      Antibiotic treatment should be continued.

PMID- 16288070
TI  - The lifestyle challenge program: a multidisciplinary approach to weight
      management.
AB  - BACKGROUND: The increasing prevalence of overweight and obesity in the US has
      received widespread attention and is highlighted in recent government-issued
      health priorities. While there are many weight loss programs in different
      settings, few include pharmacist involvement in spite of pharmacists' recognized
      easy accessibility to the public. OBJECTIVE: To provide insight into a
      successful, collaborative, multidisciplinary approach to weight management and to
      encourage pharmacists and other healthcare professionals to adopt a similar
      approach to patient management. METHODS: Adult patients >18 years of age were
      recruited from an outpatient university-based setting to participate in a weight
      management program. The principles of the program included diet, exercise, and
      behavior modification. The program was conducted through weekly one-hour group
      sessions held over a 20-week period. Faculty involved in the program included an
      attending physician specializing in nutrition, a pharmacist, and a behavioral
      psychologist. All data are expressed as mean +/- SD unless otherwise specified.
      RESULTS: Ninety participants (74 female, mean age 48 +/- 10 y) entered the
      program between April 2001 and April 2004. Participants had multiple obesity
      related comorbid diseases. The weight of completers (n = 59) decreased from 100.9
      +/- 20 kg at baseline to 97.3 +/- 19.5 kg at 10 weeks and 95.9 +/- 20 kg at 20
      weeks. Thirty-nine patients completed both baseline and final assessments, which
      showed improvement in health-related quality of life, binge-eating behavior, and
      depressive symptoms (p < 0.05). CONCLUSIONS: This program is a successful
      multidisciplinary model for the management of overweight and obese patients in an
      outpatient-based hospital setting.

PMID- 16288072
TI  - Vitamin E supplementation in Alzheimer's disease, Parkinson's disease, tardive
      dyskinesia, and cataract: Part 2.
AB  - OBJECTIVE: To review clinical trials evaluating the safety and efficacy of
      vitamin E supplementation in Alzheimer's disease, Parkinson's disease, tardive
      dyskinesia, and cataract. DATA SOURCES: Using the MeSH terms alpha-tocopherol,
      tocopherols, vitamin E, Parkinson disease, tardive dyskinesia, Alzheimer disease,
      cataract, and clinical trials, a literature review was conducted to identify peer
      reviewed articles in MEDLINE (1966-July 2005). STUDY SELECTION AND DATA
      EXTRACTION: Published materials including original research, review articles, and
      meta-analyses were reviewed. Only English-language articles and trials that
      included vitamin E alone or in combination with other vitamins or minerals were
      reviewed. Emphasis was placed on prospective, randomized, double-blind, placebo
      controlled clinical trials. DATA SYNTHESIS: The clinical studies demonstrated
      contradicting results regarding the benefits of vitamin E in Parkinson's disease,
      tardive dyskinesia, and cataract. The study reviewed for Alzheimer's disease
      seemed to show benefit when vitamin E was used; however, the statistical methods
      employed are questionable. There is enough evidence from large, well-designed
      studies to discourage the use of vitamin E in Parkinson's disease, cataract, and
      Alzheimer's disease. We recommend that vitamin E be considered a treatment option
      in patients with tardive dyskinesia only if they are newly diagnosed.
      CONCLUSIONS: We encourage patients to supplement with vitamin E-rich foods. The
      use of a daily multivitamin, which usually contains 30 IU of alpha-tocopherol,
      may be beneficial; however, we discourage individual vitamin E supplements that
      usually contain 400 IU of alpha-tocopherol.

PMID- 16288071
TI  - Effect of bupropion on sexual dysfunction.
AB  - OBJECTIVE: To determine the role of bupropion in treatment of sexual dysfunction.
      DATA SOURCES: Studies and case reports were identified through MEDLINE (1970-July
      2005) using search terms bupropion, antidepressants, sexual function, and sexual
      dysfunction. DATA SYNTHESIS: Bupropion has been shown to have a favorable effect
      on sexual dysfunction. Several reports and small, short-term trials have examined
      bupropion as an adjunct or substitute for other antidepressants in sexually
      dysfunctional patients. Use of bupropion has also been studied in nondepressed
      patients. Bupropion may be a promising medication for treating sexual
      dysfunction. However, specific dosing is unclear. CONCLUSIONS: While the studies
      reviewed here demonstrated some benefit in using bupropion to treat sexual
      dysfunction, limitations exist. Future studies should be conducted using larger
      sample sizes.

PMID- 16288073
TI  - Dose intensification with infliximab in patients with rheumatoid arthritis.
AB  - BACKGROUND: Infliximab, in combination with methotrexate, is indicated for the
      treatment of moderate to severe active rheumatoid arthritis (RA). While there is
      anecdotal evidence that many patients beginning infliximab therapy have their
      dose and/or frequency of infusions increased over time ("dose intensification"),
      relatively little is known about actual patterns of use in clinical practice.
      OBJECTIVE: To examine patterns of infliximab use in patients with RA. METHODS:
      Using a large US healthcare claims database, all patients with RA who initiated
      infliximab therapy between January 1, 2000, and September 30, 2001, were
      identified. The date of each patient's first claim for infliximab was identified
      and designated as the index date; attention was limited to patients who received
      infliximab for at least one year. Patterns of infliximab use were then examined
      over the 12-month period following the index date, based on information on paid
      claims. RESULTS: Fifty-three patients met all entry criteria; the mean age was 61
      years, and 81% were women. Twenty-eight percent of patients received >8 infusions
      over 12 months. The mean dose of infliximab at initial infusion was 296.2 mg; at
      final infusion, it was 401.9 mg (36% increase). One-half of study subjects had
      their dose of infliximab increased by > or =30% between the initial and final
      infusions; one-third had their dose increased by > or =50%. CONCLUSIONS: Many
      patients with RA beginning treatment with infliximab have their frequency of
      infusions and/or medication dose increased within the first 12 months.

PMID- 16288074
TI  - Comment: pathophysiology of mifepristone-induced septic shock due to Clostridium
      sordellii.

PMID- 16288075
TI  - Acute hyperammonemic coma with chronic valproic acid therapy.
AB  - OBJECTIVE: To report a case of dose-related hyperammonemic coma without liver
      failure in a patient receiving chronic valproate therapy. CASE SUMMARY: A 56-year
      old woman with poorly controlled epilepsy, receiving valproate at subtherapeutic
      levels for 6 years, developed a life-threatening hyperammonemic coma following a
      moderate dosage increase. DISCUSSION: Hyperammonemic coma without associated
      liver failure is an extremely rare complication of valproate therapy, described
      primarily in patients with inborn errors of metabolism and occurring
      idiosyncratically during initial stages of therapy. In our case, family history
      was suggestive of an X-linked disorder, raising the possibility that our patient
      may have been an asymptomatic carrier of a urea cycle enzyme deficiency unmasked
      by valproate therapy. To our knowledge, as of October 24, 2005, only one prior
      case of hyperammonemic coma in the context of chronic valproate monotherapy has
      been described. Application of the Naranjo probability scale score suggests that
      a causal relationship between valproic acid and hyperammonemic coma was probable.
      CONCLUSIONS: The widespread use of valproic acid emphasizes the need to maintain
      a high degree of suspicion with respect to this rare but potentially fatal
      adverse effect at all times, regardless of therapy duration.

PMID- 16288076
TI  - Acute renal failure secondary to imatinib mesylate treatment in prostate cancer.
AB  - OBJECTIVE: To report a case of acute renal failure associated with the
      administration of imatinib mesylate. CASE SUMMARY: A 64-year-old man diagnosed
      with prostate cancer was enrolled in a Phase I trial of imatinib mesylate plus
      taxotere on a protocol that required a run-in period of imatinib mesylate alone.
      During therapy with imatinib mesylate, the patient developed acute renal failure,
      requiring hemodialysis. A renal biopsy revealed tubular vacuolization. Renal
      failure resolved with cessation of imatinib mesylate. DISCUSSION: Imatinib
      mesylate is a protein tyrosine kinase inhibitor that inhibits the BCR-ABL
      tyrosine kinase, the receptor tyrosine kinases for platelet-derived growth
      factor, and stem cell factor c-kit. Prostate cancer has been identified as a
      target for therapy with imatinib mesylate. This patient had no other confounding
      factors for the cause of the renal failure. An objective causality assessment
      determined that imatinib mesylate was the probable cause of the acute renal
      failure. The presence of a primary glomerular disease was excluded by biopsy.
      CONCLUSIONS: Imatinib mesylate-induced acute renal failure has now been linked to
      toxic effects on renal tubular cells in 3 cases. Renal function should be closely
      monitored during imatinib mesylate therapy.

PMID- 16288077
TI  - Providing patient care in community pharmacies in Spain.
AB  - OBJECTIVE: To review the current status of Spanish community pharmacy, both in
      practice and research terms, and analyze its future trends. FINDINGS: Spain has a
      social security system where all citizens receive health care, social services,
      and pensions. All medical care and surgery are free for citizens; however,
      community pharmacies in Spain are privately owned. There are geographic and
      population standards for the establishment of new pharmacies, resulting in an
      average of 1 pharmacy per 2000 residents. Almost all pharmacies offer the same
      services: compounding, weight and blood pressure measurement, and cholesterol and
      glucose testing. There are also other, less-implemented services, such as
      methadone supply or directed observed treatments. Most of these services are
      freely provided, except compounding (fee for service), methadone, and directed
      observed treatments. University pharmacy practice departments do not exist in
      Spain, which leads to scarce research in this area. DISCUSSION: Efforts have been
      made to describe and measure the prevalence of negative clinical outcomes
      produced by pharmacotherapy and create an operational procedure to provide
      pharmacotherapy follow-up. CONCLUSIONS: Spain has many community pharmacies, but
      there is little pharmacy practice research. Some advanced cognitive services
      exist, but few are being remunerated.

PMID- 16288078
TI  - Myocardial infarction associated with intravenous immune globulin.
AB  - OBJECTIVE: To report a case of acute myocardial infarction (MI) experienced by a
      patient receiving intravenous immune globulin (IVIG) and review other published
      cases of MI associated with IVIG. CASE SUMMARY: An 81-year-old Vietnamese man was
      prescribed IVIG for treatment of toxic epidermal necrolysis secondary to
      allopurinol. Thirty minutes following the start of the IVIG infusion, the patient
      developed crushing retrosternal chest pain and shortness of breath. The pain
      improved upon discontinuation of IVIG infusion but recurred when IVIG was
      restarted. The troponin level reached 140 microg/L, and a persantine sestamibi
      stress test (MIBI) indicated anterolateral ischemia. The patient was diagnos ed
      with non-ST-elevation MI. An objective causality assessment using the Naranjo
      probability scale revealed a probable association between this adverse reaction
      and IVIG treatment. DISCUSSION: Although an association between IVIG
      administration and MI has not been demonstrated in clinical trials, accumulating
      clinical experience suggests that a relationship between IVIG and myocardial
      ischemia exists. Twenty published case reports were identified. Risk of acute MI
      seems to be increased with use of high-dose IVIG and in older individuals,
      especially those with at least one cardiovascular risk factor, such as ischemic
      heart disease or hypertension. CONCLUSIONS: Case reports suggest a causal
      relationship between the use of IVIG and MI and other thrombotic events. While
      cardiovascular disease is not considered an absolute contraindication to therapy,
      expanding indications and subsequent use of IVIG merit that clinicians be aware
      of patient characteristics that may increase the risk for adverse reactions and
      recognize early signs of infarction.

PMID- 16288079
TI  - Pregabalin: a new neuromodulator with broad therapeutic indications.
AB  - OBJECTIVE: To review pregabalin's pharmacology, pharmacokinetics, efficacy, and
      adverse effects in the treatment of neuropathic pain, epilepsy, and anxiety. DATA
      SOURCES: A MEDLINE search (1993-October 2005) for peer-reviewed English-language
      publications was performed. Abstracts from professional meetings were also
      included. Key terms were anxiety, diabetic neuropathy, epilepsy, neuropathic
      pain, postherpetic neuralgia, pregabalin, and seizures. STUDY SELECTION AND DATA
      EXTRACTION: Basic pharmacology data were extracted from animal studies;
      pharmacokinetic data were extracted from human studies. Multicenter, double
      blind, placebo-controlled, parallel-group studies were included to describe the
      efficacy and adverse effects of pregabalin. DATA SYNTHESIS: Pregabalin is a new
      agent that exerts its pharmacodynamic effect by modulating voltage-gated calcium
      channels. Pregabalin has a linear pharmacokinetic profile. It is completely
      absorbed, not bound to plasma proteins, not metabolized, and eliminated unchanged
      through the kidneys. Doses must be adjusted in patients with renal insufficiency.
      Clinical trials showed that pregabalin is effective in neuropathic pain
      associated with postherpetic neuralgia, diabetic peripheral neuropathy, in
      partial epilepsy as adjunctive therapy, and in generalized and social anxiety
      disorders. The most common adverse effects were dizziness and somnolence. Few
      serious adverse effects were reported. Pregabalin should not be discontinued
      rapidly. CONCLUSIONS: Pregabalin is an effective and safe analgesic,
      antiepileptic, and anxiolytic medicine. It will provide a new treatment option
      for patients with neuropathic pain and partial epilepsy.

PMID- 16288080
TI  - Drug-related emergency department visits in an elderly veteran population.
AB  - BACKGROUND: Given that adverse drug events result in extensive costs and
      healthcare resource utilization, the goal is to better understand drug-related
      emergency department (ED) visits so that programs can be implemented to improve
      the quality of health care. OBJECTIVE: To (1) determine the incidence of drug
      related ED visits at a large, tertiary care, Veterans Affairs hospital; (2)
      identify causes of these drug-related ED visits; (3) determine patient outcomes,
      healthcare resource utilization, and costs associated with these visits; and (4)
      determine the proportion of adverse drug reaction (ADR)-related ED visits that
      were spontaneously reported to the hospital's ADR reporting program. METHODS: We
      conducted a retrospective electronic chart review of all patients who visited the
      ED during the second week of each month in 2003. Causes for drug-related visits
      were identified. ADRs in this study included side effects, drug allergies, and
      drug-drug interactions (DDIs) and were assessed using the Naranjo probability
      scale. RESULTS: A total of 2169 patients were included in the study. Drug-related
      visits accounted for 12.6% of all ED visits. The main causes of drug-related
      visits were ADRs and nonadherence, which accounted for 33% and 19% of drug
      related visits, respectively. Only 11% of these ADRs were spontaneously reported
      to the hospital's ADR reporting program. Thirty-five percent of drug-related
      visits led to hospitalizations, which resulted in an average length of stay of
      9.3 days. The institution's total cost of drug-related visits was approximately
      1.5 million US dollars over 12 weeks. CONCLUSIONS: Many ED visits are drug
      related and often result in hospitalization and increased healthcare resource
      utilization. Only a minimal number of the ADRs resulting in ED visits are
      spontaneously reported to hospital ADR reporting programs.

PMID- 16288081
TI  - Search for predictors of nontherapeutic INR results with warfarin therapy.
AB  - BACKGROUND: The effectiveness and safety of warfarin require maintaining an
      international normalized ratio (INR) within the therapeutic range. OBJECTIVE: To
      identify predictors of nontherapeutic INR results in patients receiving warfarin.
      METHODS: A retrospective study was conducted using 350 ambulatory care patients
      from a broad geographic region, all receiving long-term warfarin therapy and
      followed in a tertiary-care cardiology clinic. Possible predictors of
      nontherapeutic INR results (gender, age, body weight, body mass index, height,
      race, tobacco use, alcohol use, warfarin dose, therapeutic indication, regimen
      intensity, INR monitoring frequency/category, interacting medications, adverse
      events) were assessed with logistic regression models. Subset analysis involved
      146 patients concurrently monitored with capillary whole blood INR (CoaguChek).
      RESULTS: As measured on venous specimens, 52% (182/350) of the patients had
      subtherapeutic INR results and 13% (44/350) had supratherapeutic INR results
      despite frequent (< or =4 wk) monitoring in 75% of the patients. Due to the small
      sample size, supratherapeutic INR results could not be further analyzed. Of 19
      predictors tested, only daily warfarin dose (p < 0.02) and regimen intensity (p <
      0.03) were significant independent and additive predictors of subtherapeutic
      results. Patients on the high-intensity regimen (INR 2.5-3.5) and receiving
      warfarin < or =6 mg/day had >50% risk of having subtherapeutic INR results.
      Subtherapeutic CoaguChek results were independent predictors of subtherapeutic
      venipuncture INR results in the subset (p = 0.001). CONCLUSIONS: In the absence
      of readily identifiable predictors, only higher warfarin dosing and/or more
      frequent monitoring (possibly with point-of-care/home monitoring devices) may
      minimize the time that INRs are subtherapeutic, especially in patients receiving
      low-dose and/or high-intensity anticoagulation therapy.

PMID- 16288082
TI  - A glutathione S-transferase pi-activated prodrug causes kinase activation
      concurrent with S-glutathionylation of proteins.
AB  - Nitric oxide (NO) is an endogenous, diffusible, transcellular messenger shown to
      affect regulatory and signaling pathways with impact on cell survival. Exposure
      to NO can impart direct post-translational modifications on target proteins such
      as nitration and/or nitrosylation. As an alternative, after interaction with
      oxygen, superoxide, glutathione, or certain metals, NO can lead to S
      glutathionylation, a post-translational modification potentially critical to
      signaling pathways. A novel glutathione S-transferase pi (GSTpi)-activated pro
      drug, O(2)-[2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl]1-(N,N
      dimethylamino)diazen-1-ium-1,2-diolate (PABA/NO), liberates NO and elicits
      toxicity in vitro and in vivo. We now show that PABA/NO induces nitrosative
      stress, resulting in undetectable nitrosylation, limited nitration, and high
      levels of S-glutathionylation. After a single pharmacologically relevant dose of
      PABA/NO, S-glutathionylation occurs rapidly (<5 min) and is sustained for
      approximately 7 h, implying a half-life for the deglutathionylation process of
      approximately 3 h. Two-dimensional SDS-polyacrylamide gel electrophoresis and
      immunoblotting with a monoclonal antibody to S-glutathionylated residues
      indicated that numerous proteins were S-glutathionylated. Subsequent matrix
      assisted laser desorption ionization/time of flight analysis identified 10
      proteins, including beta-lactate dehydrogenase, Rho GDP dissociation inhibitor
      beta, ATP synthase, elongation factor 2, protein disulfide isomerase,
      nucleophosmin-1, chaperonin, actin, protein tyrosine phosphatase 1B (PTP1B), and
      glucosidase II. In addition, we showed that sustained S-glutathionylation was
      temporally concurrent with drug-induced activation of the stress kinases, known
      to be linked with cell death pathways. This is consistent with the fact that
      PABA/NO induces S-glutathionylation and inactivation of PTP1B, one phosphatase
      that can participate in deactivation of kinases. These effects were consistent
      with the presence of intracellular PABA/NO or metabolites, because cells
      overexpressing MRP1 were less sensitive to the drug and had reduced levels of S
      glutathionylated proteins.

PMID- 16288083
TI  - Characterization of SIS3, a novel specific inhibitor of Smad3, and its effect on
      transforming growth factor-beta1-induced extracellular matrix expression.
AB  - This is the first report that characterizes specific inhibitor of Smad3 (SIS3) as
      a potent and selective inhibitor of Smad3 function. In the reporter assay, the
      increased luciferase activity of p3TP-lux by the overexpression of constitutively
      active form of ALK-5 was abrogated by the treatment with SIS3 in a dose-dependent
      manner. Immunoprecipitation revealed that SIS3 attenuated the transforming growth
      factor (TGF)-beta1-induced phosphorylation of Smad3 and interaction of Smad3 with
      Smad4. On the other hand, this reagent did not affect the phosphorylation of
      Smad2. Thereafter, we evaluated the ability of SIS3 in the suppression of the TGF
      beta1-induced type I procollagen up-regulation in human dermal fibroblasts. We
      found that the addition of SIS3 attenuated the effects of TGF-beta1 by reducing
      the transcriptional activity. SIS3 also inhibited the myofibroblast
      differentiation of fibroblasts by TGF-beta1. Moreover, we demonstrated that SIS3
      completely diminished the constitutive phosphorylation of Smad3 as well as the up
      regulated type I collagen expression in scleroderma fibroblasts. Together, our
      study suggested that SIS3 is a useful tool to evaluate the TGF-beta-regulated
      cellular mechanisms via selective inhibition of Smad3.

PMID- 16288084
TI  - Specific modulation of airway epithelial tight junctions by apical application of
      an occludin peptide.
AB  - Tight junctions are directly involved in regulating the passage of ions and
      macromolecules (gate functions) in epithelial and endothelial cells. The
      modulation of these gate functions to transiently regulate the paracellular
      permeability of large solutes and ions could increase the delivery of
      pharmacological agents or gene transfer vectors. To reduce the inflammatory
      responses caused by tight junction-regulating agents, alternative strategies
      directly targeting specific tight junction proteins could prove to be less toxic
      to airway epithelia. The apical delivery of peptides corresponding to the first
      extracellular loop of occludin to transiently modulate apical paracellular flux
      has been demonstrated in intestinal epithelia. We hypothesized that apical
      application of these occludin peptides could similarly modulate tight junction
      permeability in airway epithelia. Thus, we investigated the effects of apically
      applied occludin peptide on the paracellular permeability of molecular tracers
      and viral vectors in well differentiated human airway epithelial cells. The
      effects of occludin peptide on cellular toxicity, tight junction protein
      expression and localization, and membrane integrity were also assessed. Our data
      showed that apically applied occludin peptide significantly reduced
      transepithelial resistance in airway epithelia and altered tight junction
      permeability in a concentration-dependent manner. These alterations enhanced the
      paracellular flux of dextrans as well as gene transfer vectors. The occludin
      peptide redistributed occludin but did not alter the expression or distribution
      of ZO-1, claudin-1, or claudin-4. These data suggest that specific targeting of
      occludin could be a better-suited alternative strategy for tight junction
      modulation in airway epithelial cells compared with current agents that modulate
      tight junctions.

PMID- 16288088
TI  - A candid conversation about men, sexual health, and diabetes.
AB  - While the profound relationship between human sexuality and diabetes can affect
      quality of life for both men and women, male sexual health issues in the
      published literature have primarily focused on physical aspects of erectile
      dysfunction. The purpose of this article is to move this important discussion
      regarding aspects of human sexuality and diabetes further to consider the absence
      of and need for more male-focused research. Attention is given to define and
      discuss how male perceptions of control and masculinity shape male views on male
      sex roles. The author offers 4 published explanations to explain factors that
      influence whether men, regardless of age, nationality, or ethnic group, initiate
      help-seeking behaviors for sexual health concerns. These explanations can help
      health care professionals have candid, consistent, and nonjudgmental
      conversations with their patients and each other. This article concludes with
      strong recommendations that health care providers engage patients in timely
      conversations, jointly select and implement tailored treatment options, and, when
      necessary, link patients with social support systems to maximize improvements in
      both physical and psychological aspects of sexual health.

PMID- 16288089
TI  - Implementation of a new intravenous insulin method on intermediate-care units in
      hospitalized patients.
AB  - Good blood glucose control in hospitalized adults leads to reduced mortality.
      Intravenous (IV) insulin has been shown to be an effective way to achieve tight
      control of blood glucose. Managing IV insulin is a labor-intensive task for
      nurses and is generally done in intensive care units with high nurse-to-patient
      ratios. In this 3-month study, intermediate-care general medicine units with a
      nurse-to-patient ratio of 1 to 5 or 6 were evaluated for effectiveness of
      monitoring IV insulin. The project, which relied on intensive in-service
      education, an audit tool, and continuous positive feedback for nurses, yielded
      positive results.

PMID- 16288090
TI  - Internet communities: do they improve coping with diabetes?
AB  - The purpose of this study was to establish and evaluate a Web-based educational
      and emotional resource for patients with diabetes and their family members.
      Activity and characteristics of 331 953 user visits were tracked over 74 months,
      including a survey of user satisfaction. A 2004 survey showed that users were
      from 37 different countries, with most from the United States (87%) and Canada
      (4%). The average length of use was 16:44 minutes. Respondents (n = 791) to the
      satisfaction survey were 71% female, 46% were insulin users, 84% were aged >30
      years, 34% had diabetes >10 years, and 39% visited more than 3 times. A total of
      74% of all respondents rated participation in the discussion board as having a
      positive effect on coping with diabetes, and 71% rated participation as helping
      them to feel more hopeful. A professionally moderated Internet discussion group
      appears to be a useful strategy for engaging patients with diabetes and
      increasing perceived ability to cope with diabetes.

PMID- 16288091
TI  - Use of continuous subcutaneous insulin infusion pump in patients with type 2
      diabetes mellitus.
AB  - PURPOSE: In patients with type 2 diabetes, the control of hyperglycemia is often
      difficult despite full doses of oral hypoglycemic agents and extremely large
      doses of insulin. These patients pose a major management problem. The authors
      therefore investigated whether insulin given as a subcutaneous continuous
      infusion of insulin (CSII) would result in an improvement in glucose homeostasis.
      METHODS: Four patients with badly controlled type 2 diabetes, on treatment with
      extremely high doses of insulin and oral hypoglycemic agents, were started on
      CSII. RESULTS: All four patients had a marked improvement in plasma glucose
      concentrations with a corresponding fall in HbA1c levels. This improvement was
      associated with a marked fall in the insulin doses necessary to maintain adequate
      glucose homeostasis. CONCLUSIONS: Since HbA1c levels fell from levels that would
      be associated with diabetic complications to those at which complications are
      markedly reduced, we recommend that patients with type 2 diabetes uncontrolled on
      extremely high doses of insulin be given a trial of treatment with CSII.

PMID- 16288092
TI  - Use of continuous subcutaneous insulin infusion (insulin pump) therapy in the
      hospital setting: proposed guidelines and outcome measures.
AB  - PURPOSE: Individuals whose diabetes is being treated in the outpatient setting
      via an insulin pump often wish to maintain this therapy during hospitalization.
      The authors propose guidelines for management of patients on insulin pumps who
      require a hospital admission. METHODS: A collaborative interinstitutional task
      force reviewed current available information regarding the use of insulin pumps
      in the hospital. RESULTS: There was little information in the medical literature
      on how to manage individuals on established insulin pump therapy during a
      hospital stay. The task force believed that a policy that promotes patient
      independence through continuation of insulin pump therapy while ensuring patient
      safety was possible. A set of contraindications for continued use of pump therapy
      in the hospital are proposed. A sample patient consent form and order set are
      presented. Finally, measures that can be used to assess effectiveness of an
      inpatient insulin pump policy are outlined. CONCLUSIONS: Patients on established
      insulin pump therapy do not necessarily have to discontinue treatment while
      hospitalized. However, clear policies and procedures should be established at the
      institutional level to guide continued use of the technology in the acute care
      setting.

PMID- 16288093
TI  - Diabetes nurse educators' prioritized elder foot care behaviors.
AB  - PURPOSE: The purpose of this study was to identify diabetes nurse educators'
      perceptions of the most important foot care behaviors for elderly people to enact
      in daily care. METHODS: A structured, open-ended questionnaire was mailed to a
      regionally stratified random sample of 90 diabetes nurse educators. Subjects were
      asked to identify and rank order 8 foot care behaviors perceived important for
      elderly people with diabetes to enact daily. Data were transcribed and coded into
      categories and domains using descriptive content analysis. RESULTS: Forty-seven
      diabetes nurse educators responded with a total of 346 foot care behaviors
      perceived important for elders. Twenty-one major foot care behavior content
      categories were grouped into 4 domains of descending importance: foot/nail care,
      footwear/shoes, general health, and foot emergencies. CONCLUSIONS: Diabetes nurse
      educators generated a range of baseline data for developing a reliable, valid,
      and patient foot care knowledge outcome measure to support national diabetes
      patient education and self-management program guidelines.

PMID- 16288094
TI  - "I help you, and you help me": facilitated telephone peer support among patients
      with diabetes.
AB  - PURPOSE: The feasibility and acceptability of using an Interactive Voice Response
      (IVR)-based platform to facilitate peer support among older adults with diabetes
      was evaluated. METHODS: Diabetes patients with poor glycemic control receiving
      care at a Veterans' Affairs medical center completed a baseline survey, received
      rudimentary training, and were matched based on their diabetes-related self
      management needs. They were asked to contact their partner weekly using the toll
      free IVR calling line. At the completion of the 6-week period, participants
      completed follow-up surveys and brief telephone interviews. RESULTS: Forty of 76
      patients screened for eligibility by telephone agreed to participate, and 38
      completed the 6-week intervention (50% of eligible patients). More than 80% of
      the pairs spoke at least once a week for 2 of the 6 weeks of the intervention. A
      total of 79% of the participants reported that the IVR system was easy to use,
      and 90% stated that they would be more satisfied with their health care if this
      type of peer support service were available. Of the participants, 70% found the
      calls helpful in managing diabetes symptoms, 73% reported that their partner
      helped them improve their self-care, and 70% stated that they helped their
      partner do things to stay healthy. There were significant improvements in
      participants' reported diabetes self-care self-efficacy between baseline and
      follow-up assessments (P < .01). Qualitative assessments suggested that
      participants found meaning and positive reinforcement for their own self-care
      through supporting their partner's efforts to manage diabetes. CONCLUSIONS: An
      IVR peer support intervention is feasible, acceptable to patients, and may have
      positive effects on patients' diabetes self-management and health outcomes that
      warrant more rigorous evaluation in a randomized trial.

PMID- 16288095
TI  - Translational research principles of an effectiveness trial for diabetes care in
      an urban African American population.
AB  - PURPOSE: Large-scale effectiveness trials designed to translate evidence-based
      diabetes care to community settings are few. Studies describing these methods
      among high-risk minority populations are particularly limited. METHODS: The
      authors describe Project Sugar, a randomized controlled trial conducted in 2
      phases: Project Sugar 1 (1994-1999), which piloted a 4-arm clinic and home-based
      intervention using nurse case management and community health workers in 186
      urban African Americans with type 2 diabetes, and Project Sugar 2 (2000-2005),
      which examined effectiveness of this intervention among 542 diabetic, urban
      African Americans. Results and Conclusions Project Sugar had success with regard
      to recruitment and retention, both in phase 1 (80% rate at 24 months) and phase 2
      (>90% at 24 months). Using the RE-AIM framework, planning and research design for
      Project Sugar 2 is described in detail for elements that contributed to the
      reach, effectiveness, adoption, implementation, and maintenance of this study
      within a minority community setting. In addition to successful strategies,
      challenges to conducting effectiveness trials in an inner-city African American
      community are identified.

PMID- 16288096
TI  - Barriers associated with the delivery of Medicare-reimbursed diabetes self
      management education.
AB  - PURPOSE: The purpose of this study was to explore the barriers that practitioners
      face in providing diabetes self-management education (DSME) to Medicare
      beneficiaries, with a special focus on barriers faced by rural providers.
      METHODS: Using an e-mail survey, Diabetes Control Program Coordinators (DCPCs) in
      all US states were asked 3 open-ended questions to understand problems with
      obtaining American Diabetes Association (ADA) recognition for Medicare
      reimbursement, differences in obtaining ADA recognition by rural and urban
      facilities, and facility-level barriers to providing DSME to Medicare patients.
      Using a mail survey administered to half of ADA-recognized diabetes education
      centers (DECs), information was collected about perceived barriers to providing
      DSME in all areas and rural areas. RESULTS: Most DCPCs believed it was more
      difficult for rural providers to obtain ADA recognition than for urban providers;
      the largest barriers were costs and reporting requirements. The top barriers for
      rural providers mentioned by DCPCs were the shortage of designated specialists,
      fewer resources, and high application fees for ADA recognition. Barriers
      identified by DEC respondents facing rural providers include
      staffing/institutional support, amount of Medicare reimbursement, lack of hours
      covered, and transportation. DEC respondents providing care in urban areas only
      were more likely to perceive barriers to providing diabetes education in rural
      areas than were rural providers. CONCLUSIONS: Barriers to DSME are perceived to
      be higher for rural providers than urban providers. Urban providers perceived
      that many barriers to DSME are greater for rural providers. The ADA application
      process is perceived as expensive and laborious. Most respondents perceived
      Medicare reimbursement for DSME as inadequate.

PMID- 16288098
TI  - Does airway inflation stretch the bronchial mucosal membrane?

PMID- 16288097
TI  - Automated microscopy screening for compounds that partially revert cholesterol
      accumulation in Niemann-Pick C cells.
AB  - Niemann-Pick disease type C (NPC) is an autosomal recessive genetic disorder
      manifested by abnormal accumulation of unesterified cholesterol and other lipids.
      We screened combinatorially synthesized chemical libraries to identify compounds
      that would partially revert cholesterol accumulation. Cultured CHO cells with NPC
      phenotypes (CT60 and CT43) were used for screening along with normal CHO cells as
      a control. We developed an automated microscopy assay based on imaging of filipin
      fluorescence for estimating cholesterol accumulation in lysosomal storage
      organelles. Our primary screen of 14,956 compounds identified 14 hit compounds
      that caused significant reduction in cellular cholesterol accumulation at 10
      microM. We then screened a secondary library of 3,962 compounds selected based on
      chemical similarity to the initial hits and identified 7 compounds that
      demonstrated greater efficacy and lower toxicity than the original hits. These
      compounds are effective at concentrations of 123 nM to 3 microM in reducing the
      cholesterol accumulation in cells with a NPC1 phenotype.

PMID- 16288099
TI  - Short-term effects of axillary lymph node clearance surgery on lymphatic
      physiology of the arm in breast cancer.
AB  - It is not known why some women develop breast cancer-related lymphedema (BCRL) of
      the arm, whereas others having similar treatment do not. We speculated that
      increased uptake of protein into local blood may protect against BCRL. Sixteen
      women were given bilateral subcutaneous hand webspace injections of polyclonal
      immunoglobulin (HIgG), (99m)Tc-HIgG on one side and (111)In-HIgG on the other,
      before and 3 mo after axillary clearance surgery. The rates of clearance of
      activity from the depot (k) and accumulation in central blood (b(contra)) were
      measured using a scintillation probe and bilateral antecubital vein blood
      sampling, respectively. Activity accumulating in blood ipsilateral to the
      injected side, in excess of central blood activity (b(ipsi)) was also calculated
      as a measure of local vascular uptake. The k correlated with b(contra), but
      neither changed in response to surgery. However, b(ipsi) for injections of
      (99m)Tc-HIgG into the affected arm increased in all seven patients in whom data
      were available (0.018 +/- 0.006 to 0.038 +/- 0.007%/min; P < 0.05); indeed, in
      five of these seven, b(ipsi) paradoxically exceeded b(contra), and none developed
      BCRL at 3-yr follow-up. We conclude that uptake of protein into local blood
      and/or proteolysis increases after axillary surgery and may protect against BCRL.

PMID- 16288100
TI  - Myofiber degeneration/regeneration is induced in the cachectic ApcMin/+ mouse.
AB  - Cachexia is characterized as an inflammatory state induced by the cancer
      environment, which is accompanied by the loss of muscle and fat mass. Well
      investigated mechanisms of cachexia include the suppression of myofiber protein
      synthesis and the induction of the protein degradation. However, it is not well
      characterized whether chronic inflammation during cachexia induces myofiber
      degeneration, which contributes to muscle mass loss and decreased functional
      capacity. The purpose of this study was to determine whether Apc(Min/+) mice,
      which demonstrate a chronic systemic inflammatory state due to an intestinal
      tumor burden, undergo cachexia and whether the myofibers exhibit signs of
      degeneration and/or regeneration. Six-month-old female Apc(Min/+) body weight
      decreased 21% compared with C57BL/6 mice and was not the result of blunted
      growth. Apc(Min/+) gastrocnemius muscle was reduced 45%, and soleus mean fiber
      cross-sectional area decreased 24% vs. C57BL/6 mice. Soleus muscle morphology
      demonstrated pathology of myofibers undergoing degeneration and/or regeneration.
      These data demonstrate that the Apc(Min/+) mouse becomes cachectic by 6 mo of age
      and that skeletal muscle degeneration and regeneration may be related to the
      muscle loss.

PMID- 16288101
TI  - Influence of cardiac function and failure on sleep-disordered breathing: evidence
      for a causative role.
AB  - Heart failure is an increasingly common public health problem that is strongly
      linked to both central and obstructive sleep apnea, collectively referred to as
      sleep-disordered breathing. Much attention has been given to the deleterious
      effects of sleep-disordered breathing on the failing heart and potential
      mechanisms by which treatment of sleep-disordered breathing may result in
      improved cardiac performance and long-term outcomes. However, there is compelling
      evidence that cardiac dysfunction may contribute to sleep-disordered breathing.
      Although there is recognized overlap between pathophysiological mechanisms in
      central sleep apnea and obstructive sleep apnea, data supporting the role of
      cardiac function are certain forms of central sleep apnea are well established,
      whereas investigation into the relationship with obstructive sleep apnea is less
      mature but continues to evolve. This review will examine experimental and
      observational data that explore possible pathophysiological mechanisms and
      potential targets for therapy in heart failure and sleep-disordered breathing.

PMID- 16288102
TI  - Pathogenesis of obstructive sleep apnea.
AB  - The pathogenesis of obstructive sleep apnea (OSA) has been under investigation
      for over 25 years, during which a number of factors that contribute to upper
      airway (UA) collapse during sleep have been identified. Structural/anatomic
      factors that constrict space for the soft tissues surrounding the pharynx and its
      lumen are crucial to the development of OSA in many patients. Enlargement of soft
      tissues enveloping the pharynx, including hypertrophied tonsils, adenoids, and
      tongue, is also an important factor predisposing to UA collapse, inasmuch as this
      can impinge on the pharyngeal lumen and narrow it during sleep. Other factors,
      including impairment of UA mechanoreceptor sensitivity and reflexes that maintain
      pharyngeal patency and respiratory control system instability, have also been
      identified as possible mechanisms facilitating UA instability. This suggests that
      OSA may be a heterogeneous disorder, rather than a single disease entity.
      Therefore, the extent to which various pathogenic factors contribute to the
      phenomenon of repetitive collapse of the UA during sleep probably varies from
      patient to patient. Further elucidation of specific pathogenic mechanisms in
      individuals with OSA may facilitate the development of new therapies that can be
      tailored to individual patient needs according to the underlying mechanism(s) of
      their disease.

PMID- 16288103
TI  - Comment on Point:Counterpoint "The muscle pump is/is not an important determinant
      of muscle blood flow during exercise".

PMID- 16288105
TI  - Comments on Point:Counterpoint "Positive effects of intermittent hypoxia (live
      high:train low) on exercise performance are/are not mediated primarily by
      augmented red cell volume".

PMID- 16288104
TI  - Comment on Point:Counterpoint "Flow-mediated dilation does/does not reflect
      nitric oxide-mediated endothelial function".

PMID- 16288106
TI  - Kinetics of muscle oxygen use, oxygen content, and blood flow during exercise.

PMID- 16288107
TI  - MRI of pharyngeal airway in children with sleep-disordered breathing.

PMID- 16288108
TI  - Eu-estrogenemia.

PMID- 16288109
TI  - A comment on Burgomaster et al. and a general plea to consider behavioral
      influences in human physiology studies.

PMID- 16288110
TI  - RARbeta1': primed to fight retinoid resistance in lung carcinogenesis.

PMID- 16288111
TI  - Deguelin as a chemopreventive agent in mouse lung tumorigenesis induced by
      tobacco smoke carcinogens.

PMID- 16288113
TI  - Latest HapMap update aims to direct researchers to genetic basis of disease.

PMID- 16288112
TI  - Bernard Fisher reflects on a half-century's worth of breast cancer research.

PMID- 16288114
TI  - Stat bite: Lung cancer incidence by sex and ethnicity, 1973-2002.

PMID- 16288115
TI  - Clinical trial transparency: registries, databases raise questions, stir debate.

PMID- 16288116
TI  - Researchers exploring implications of minimal residual cancer.

PMID- 16288118
TI  - Tamoxifen for the prevention of breast cancer: current status of the National
      Surgical Adjuvant Breast and Bowel Project P-1 study.
AB  - BACKGROUND: Initial findings from the National Surgical Adjuvant Breast and Bowel
      Project Breast Cancer Prevention Trial (P-1) demonstrated that tamoxifen reduced
      the risk of estrogen receptor-positive tumors and osteoporotic fractures in women
      at increased risk for breast cancer. Side effects of varying clinical
      significance were observed. The trial was unblinded because of the positive
      results, and follow-up continued. This report updates our initial findings.
      METHODS: Women (n = 13,388) were randomly assigned to receive placebo or
      tamoxifen for 5 years. Rates of breast cancer and other events were compared by
      the use of risk ratios (RRs) and 95% confidence intervals (CIs). Estimates of the
      net benefit from 5 years of tamoxifen therapy were compared by age, race, and
      categories of predicted breast cancer risk. Statistical tests were two-sided.
      RESULTS: After 7 years of follow-up, the cumulative rate of invasive breast
      cancer was reduced from 42.5 per 1000 women in the placebo group to 24.8 per 1000
      women in the tamoxifen group (RR = 0.57, 95% CI = 0.46 to 0.70) and the
      cumulative rate of noninvasive breast cancer was reduced from 15.8 per 1000 women
      in the placebo group to 10.2 per 1000 women in the tamoxifen group (RR = 0.63,
      95% CI = 0.45 to 0.89). These reductions were similar to those seen in the
      initial report. Tamoxifen led to a 32% reduction in osteoporotic fractures (RR =
      0.68, 95% CI = 0.51 to 0.92). Relative risks of stroke, deep-vein thrombosis, and
      cataracts (which increased with tamoxifen) and of ischemic heart disease and
      death (which were not changed with tamoxifen) were also similar to those
      initially reported. Risks of pulmonary embolism were approximately 11% lower than
      in the original report, and risks of endometrial cancer were about 29% higher,
      but these differences were not statistically significant. The net benefit
      achieved with tamoxifen varied according to age, race, and level of breast cancer
      risk. CONCLUSIONS: Despite the potential bias caused by the unblinding of the P-1
      trial, the magnitudes of all beneficial and undesirable treatment effects of
      tamoxifen were similar to those initially reported, with notable reductions in
      breast cancer and increased risks of thromboembolic events and endometrial
      cancer. Readily identifiable subsets of individuals comprising 2.5 million women
      could derive a net benefit from the drug.

PMID- 16288117
TI  - A novel retinoic acid receptor beta isoform and retinoid resistance in lung
      carcinogenesis.
AB  - BACKGROUND: We previously reported that all-trans-retinoic acid (RA) treatment
      can prevent in vitro transformation of immortalized human bronchial epithelial
      (HBE) cells. METHODS: To determine whether methylation inhibits RARbeta
      expression in HBE cells, we used sodium bisulfite sequencing to compare RARbeta
      P2 promoter methylation patterns in RA-sensitive (BEAS-2B) and RA-resistant (BEAS
      2B-R1) HBE cells. Immunoblotting was used to assess induction of the RARbeta,
      placental transforming growth factor beta (PTGF-beta), Fos-related antigen 1 (Fra
      1), and transglutaminase II (TGase II) proteins by RA following treatment with
      azacitidine, a DNA demethylating agent. The expression, transcriptional activity,
      and growth suppressive activity of RARbeta1', a novel RAR isoform, were evaluated
      in lung cancer cells transfected with RARbeta1', and expression was also studied
      in paired normal lung tissues and lung tumors. All statistical tests were two
      sided. RESULTS: Hypermethylation was observed in the 3' region of the RARbeta P2
      promoter of BEAS-2B-R1 but not BEAS-2B cells. Azacitidine treatment of BEAS-2B-R1
      cells restored RA-inducible RARbeta2 and PTGF-beta expression but not that of
      RARbeta1', Fra-1, or TGase II. RARbeta1' expression was repressed in RA-resistant
      BEAS-2B-R1 cells and in lung cancers, compared with adjacent normal lung tissues.
      BEAS-2B-R1 cells transiently transfected with RARbeta1' had increased RA
      dependent activation of a retinoic acid receptor element (RARE)-containing
      reporter plasmid compared with vector control (mean = 3.2, 95% confidence
      interval [CI] = 3.1 to 3.3 versus mean = 1.4, 95% CI = 1.3 to 1.5; P<.001). In
      H358 lung cancer cells transiently transfected with RARbeta1', RA treatment
      restored target gene expression compared with that in vector-transfected cells
      and suppressed cell growth compared with that in untreated cells (4 microM;
      treated mean = 0.49 versus untreated mean = 1.0, difference = 0.51, 95% CI = 0.35
      to 0.67, P = .003; 8 microM: treated mean = 0.50 versus untreated mean = 1.0,
      difference = 0.50, 95% CI = 0.26 to 0.74, P = .015). CONCLUSION: Restoration of
      RARbeta1' expression may overcome retinoid resistance in lung carcinogenesis.

PMID- 16288119
TI  - Vaccination with cetuximab mimotopes and biological properties of induced anti
      epidermal growth factor receptor antibodies.
AB  - BACKGROUND: The monoclonal antibody cetuximab (IMC-225, Erbitux) inhibits
      epidermal growth factor receptor (EGFR) signaling and has been approved for
      metastatic colon cancer therapy. However, to achieve effective titers, passive
      antibody therapies must be repeatedly administered over long periods. To overcome
      this limitation, we aimed to generate a vaccine inducing continuously available
      "cetuximab-like" antibodies in vivo using the mimotope approach. METHODS: We used
      the phage display technique to identify four peptides structurally mimicking the
      cetuximab epitope. We coupled two of these peptides to an immunogenic carrier
      protein, and we vaccinated four groups (n = 8) of BALB/c mice intraperitoneally
      with 10 microg of the mimotope conjugates, a control peptide conjugate, or the
      carrier protein alone. We assessed antibody-dependent cellular cytotoxicity and
      complement-dependent cytotoxicity mediated by the induced antibodies against EGFR
      overexpressing human A431 carcinoma cells. We then tested receptor
      internalization capacity of the induced antibodies with fluorescently labeled
      EGFR, and we assayed their growth inhibitory potential toward A431 cells with a
      [3H]thymidine proliferation assay. RESULTS: Mimotope-induced antibodies
      recognized EGFR, and both types of antibody-mediated cytotoxic effects were
      elicited by these antibodies. In both cellular cytotoxicity assays, the mimotope
      induced antibodies exhibited specific lysis of more than 50%. The induced
      antibodies caused internalization of the receptor from the cell surface into
      endocytic vesicles and inhibited growth of EGFR-expressing cells to a similar
      extent as cetuximab [67% (95% confidence interval {CI} = 55% to 79%) and 69% (95%
      CI = 55% to 84%), respectively]. CONCLUSIONS: Epitope-specific immunization is
      feasible for active anti-EGFR immunotherapy. The in vitro biologic features of
      mimotope-induced antibodies are similar to those of the monoclonal antibody
      cetuximab.

PMID- 16288120
TI  - Lifetime recreational exercise activity and breast cancer risk among black women
      and white women.
AB  - BACKGROUND: Physical inactivity is a potentially modifiable breast cancer risk
      factor. Because few data on this relationship exist for black women, we examined
      the relationship between breast cancer risk and lifetime and time- or age
      specific measures of recreational exercise activity among white women and among
      black women. METHODS: The Women's Contraceptive and Reproductive Experiences
      Study was a multicenter population-based case-control study of black women and
      white women aged 35-64 years with newly diagnosed invasive breast cancer. We
      collected detailed histories of lifetime recreational exercise activity during in
      person interviews with 4538 case patients with breast cancer (1605 black and 2933
      white) and 4649 control subjects (1646 black and 3033 white). Control subjects
      were frequency-matched to case patients on age, race, and study site. We examined
      associations between exercise activity measures (metabolic equivalents of energy
      expenditure [MET]-hours per week per year) and breast cancer risk overall and
      among subgroups defined by race, other breast cancer risk factors, and tumor
      characteristics by use of unconditional logistic regression. All statistical
      tests were two-sided. RESULTS: Among all women, decreased breast cancer risk was
      associated with increased levels of lifetime exercise activity (e.g., average MET
      hours per week per year, P(trend) = .002). An average annual lifetime exercise
      activity that was greater than the median level for active control subjects was
      associated with an approximately 20% lower risk of breast cancer, compared with
      that for inactivity (for 6.7-15.1 MET-hours/week/year, odds ratio [OR] = 0.82,
      95% confidence interval [CI] = 0.71 to 0.93; for > or =15.2 MET-hours/week/year,
      OR = 0.80, 95% CI = 0.70 to 0.92). The inverse associations did not differ
      between black and white women (for MET-hours/week/year, P(trend) = .003 and
      P(trend) = .09, respectively; homogeneity of trends P = .16). No modification of
      risk was observed by disease stage, estrogen receptor status, or any breast
      cancer risk factor other than first-degree family history of breast cancer.
      CONCLUSIONS: This study supports an inverse association between physical activity
      and breast cancer among black women and among white women.

PMID- 16288121
TI  - Diabetes mellitus and risk of colorectal cancer: a meta-analysis.
AB  - BACKGROUND: Diabetes has been associated with an increased risk of colorectal
      cancer in most, but not all, studies. Findings have also been inconclusive with
      regard to sex and subsite in the colorectum. To resolve these inconsistencies, we
      conducted a meta-analysis of published data on the association between diabetes
      and the incidence and mortality of colorectal cancer. METHODS: We identified
      studies by a literature search of Medline from January 1, 1966, through July 31,
      2005, and by searching the reference lists of pertinent articles. Summary
      relative risks (RRs) with 95% confidence intervals (CIs) were calculated with a
      random-effects model. All statistical tests were two-sided. RESULTS: Analysis of
      15 studies (six case-control and nine cohort studies), including 2 593 935
      participants, found that diabetes was associated with an increased risk of
      colorectal cancer, compared with no diabetes (summary RR of colorectal cancer
      incidence = 1.30, 95% CI = 1.20 to 1.40), without heterogeneity between studies
      (P(heterogeneity) = .21). These results were consistent between case-control and
      cohort studies and between studies conducted in the United States and in Europe.
      The association between diabetes and colorectal cancer incidence did not differ
      statistically significantly by sex (summary RR among women = 1.33, 95% CI = 1.23
      to 1.44; summary RR among men = 1.29, 95% CI = 1.15 to 1.44; P(heterogeneity) =
      .26) or by cancer subsite (summary RR for colon = 1.43, 95% CI = 1.28 to 1.60;
      summary RR for rectum = 1.33, 95% CI = 1.14 to 1.54; P(heterogeneity) = .42).
      Diabetes was positively associated with colorectal cancer mortality (summary RR =
      1.26, 95% CI = 1.05 to 1.50), but there was evidence for heterogeneity between
      studies (P(heterogeneity) = .04). CONCLUSIONS: Our findings strongly support a
      relationship between diabetes and increased risk of colon and rectal cancer in
      both women and men.

PMID- 16288122
TI  - Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective
      study.
AB  - BACKGROUND: Adiponectin is an insulin-sensitizing hormone secreted by adipocytes.
      Levels of adiponectin are inversely associated with adiposity and insulin
      resistance. Because both adiposity and insulin resistance have been associated
      with risk of colorectal cancer, we hypothesized that adiponectin is associated
      with colorectal carcinogenesis. METHODS: We evaluated the association between
      adiponectin and colorectal cancer among 18 225 men in the Health Professionals
      Follow-up Study who provided blood samples in 1994. Between blood collection and
      January 31, 2002, 179 incident colorectal cancer cases occurred. Each case
      patient was matched to two control subjects on year of birth and date of blood
      draw. Information on lifestyle factors and diet was collected using biennial
      questionnaires and food frequency questionnaires. Logistic regression models were
      used to estimate relative risks (RRs) and confidence intervals (CIs). All
      statistical tests were two-sided. RESULTS: We observed a statistically
      significant inverse association between plasma adiponectin levels and risk of
      colorectal cancer (for the highest quintile [Q5] versus the lowest quintile [Q1],
      RR = 0.42, 95% CI = 0.23 to 0.78; P(trend) = .01). The association was only
      slightly attenuated after adjustment for body mass index (Q5 versus Q1, RR =
      0.48, 95% CI = 0.25 to 0.90; P(trend) = .04) or for body mass index and other
      major risk factors for colorectal cancer (family history, physical activity,
      multivitamin use, smoking, alcohol, aspirin use, history of endoscopy, dietary
      calcium, folate, vitamin E, and vitamin D; Q5 versus Q1, multivariable RR = 0.50,
      95% CI = 0.26 to 0.97; P(trend) = .08). Relative risks were not linear in any of
      the analyses; the second quintile had a lower relative risk than the lowest
      quintile, but further decreases in risk were not evident with increasing levels
      of adiponectin. CONCLUSIONS: In this prospective nested case-control study, men
      with low plasma adiponectin levels had a higher risk of colorectal cancer than
      men with higher levels. More prospective observational studies, particularly in
      women, and mechanistic studies are required to fully understand the relationship
      between adiponectin and carcinogenesis.

PMID- 16288123
TI  - Chemopreventive effects of deguelin, a novel Akt inhibitor, on tobacco-induced
      lung tumorigenesis.
AB  - Tobacco carcinogens induce Akt activation and lung carcinogenesis. We previously
      demonstrated that deguelin, a natural plant product, specifically inhibits the
      proliferation of premalignant and malignant human bronchial epithelial cells by
      blocking Akt activation. To evaluate the ability of deguelin to block tobacco
      carcinogen-induced lung tumorigenesis, we evaluated the in vivo effects of
      deguelin on Akt activation and lung tumorigenesis in transgenic mice in which Akt
      expression was induced by tamoxifen and in 4-(methylnitrosoamino)-1-(3-pyridyl)-1
      butanone (NNK)/benzo(a)pyrene (BaP)-treated A/J mice. Deguelin suppressed Akt
      activation in vivo, as measured by immunohistochemistry and immunoblotting, and
      statistically significantly reduced NNK/BaP-induced lung tumor multiplicity,
      volume, and load in A/J mice, as monitored by microcomputed tomography image
      analysis, with no detectable toxicity. These results indicate that deguelin
      warrants consideration as a chemopreventive agent for early-stage lung
      carcinogenesis in a clinical lung cancer chemoprevention trial.

PMID- 16288124
TI  - Impact of hysterectomy on endometrial carcinoma rates in the United States.
AB  - In the United States, endometrial carcinoma incidence rates, uncorrected for
      hysterectomy prevalence, are higher among white women than black women. We
      estimated corrected endometrial carcinoma rates by racial/ethnic groups and age
      (30-74 years) for 1992-2000 using data from the Surveillance, Epidemiology, and
      End Results program and the Behavioral Risk Factor Surveillance Survey.
      Hysterectomy prevalence was higher among black women than among Hispanic and
      white non-Hispanic women. Correcting for hysterectomy prevalence increased age
      adjusted endometrial carcinoma rates per 10(5) woman-years from 29.2 to 48.7
      (66.8% increase) overall, from 14.6 to 28.5 (95.3% increase) in blacks, from 18.8
      to 29.6 (57.6% increase) in Hispanics, and from 33.2 to 54.9 (65.1%) in white non
      Hispanics. This correction reduced the rate ratio for white non-Hispanics
      compared with blacks from 2.27 to 1.93. Among blacks but not Hispanics or white
      non-Hispanics, the endometrial carcinoma risk factors of obesity and diabetes
      were more prevalent among hysterectomized than nonhysterectomized women. Failure
      to correct for hysterectomy prevalence may lead to underestimates of endometrial
      carcinoma risk, especially among blacks. The high prevalence of hysterectomy
      among blacks with strong endometrial cancer risk factors may partly account for
      lower cancer rates in this group.

PMID- 16288125
TI  - Re: Efficacy of breast cancer screening in the community according to risk level.

PMID- 16288126
TI  - Re: Efficacy of breast cancer screening in the community according to risk level.

PMID- 16288127
TI  - Re: Colon cancer survival rates with the new American Joint Committee on Cancer
      sixth edition staging.

PMID- 16288128
TI  - Delirium associated with baclofen withdrawal: a review of common presentations
      and management strategies.
AB  - The authors reviewed 23 published cases of psychiatric symptoms in association
      with baclofen withdrawal. Delirium, and not other functional psychiatric
      conditions, arose secondarily from abrupt baclofen cessation. Vulnerability to
      baclofen-withdrawal delirium appeared to be greater in individuals who received
      chronic baclofen therapy. Baclofen-withdrawal delirium can be difficult to
      distinguish from delirium of other etiologies, and unrecognized and inadequately
      treated baclofen-withdrawal delirium is associated with significant morbidity and
      mortality. Complete resolution of delirium symptoms was possible with
      reinstatement of baclofen. The clinical management of patients experiencing
      baclofen-withdrawal delirium includes supportive interventions to reduce
      complications of delirium until symptoms resolve.

PMID- 16288129
TI  - The impact of medical illness on executive function.
AB  - Executive function can be defined as one's ability to plan, initiate, sequence,
      monitor, and inhibit complex goal-directed behaviors. Although executive
      impairment is generally associated with dementia, recent studies have suggested
      that patients with chronic diseases, such as hypertension, chronic obstructive
      pulmonary disease, and diabetes, may also have executive deficits independent of
      psychiatric comorbidities. Because executive function is associated with
      functional outcomes, medication compliance, and the capacity to give informed
      consent, it is important that it be assessed. However, it is the authors'
      impression that executive function is not adequately assessed in medical
      settings, despite the availability of reliable measures. This article reviews the
      impact of medical illness on executive function and discusses practical
      diagnostic instruments and treatment strategies. The changes in functional status
      associated with executive impairment as well as pathophysiology and treatment
      strategies are also discussed.

PMID- 16288131
TI  - Association between depressive episode before first myocardial infarction and
      worse cardiac failure following infarction.
AB  - Depression following myocardial infarction is associated with a higher mortality
      rate. The authors studied 314 patients admitted to the hospital with a first
      myocardial infarction to assess whether cardiac failure after the infarction,
      which is also linked to a higher mortality rate, was predicted by psychosocial
      characteristics present before the myocardial infarction. One-fifth (20.7%) of
      the subjects met the ICD-10 criteria for depressive episode in the 1 month before
      the attack. Variables independently associated with worse cardiac failure after
      the myocardial infarction were greater age, a history of angina preceding the
      infarction, and a previous depressive episode. The impact of depression on
      postinfarction outcome may result from the influence of preinfarction depression
      on the degree of cardiac failure.

PMID- 16288130
TI  - Psychiatric sequelae following breast cancer chemotherapy: a pilot study using
      claims data.
AB  - Despite attention to depression and cognitive disorders, the prevalence of other
      mental disorders following breast cancer chemotherapy has not been well
      described. The authors undertook a pilot study using insurance claims data to
      compare the prevalence of mental disorders other than depression in a population
      of breast cancer surgery patients who did versus did not receive postsurgical
      chemotherapy treatment. Women receiving chemotherapy in addition to surgery were
      more likely to be diagnosed with adjustment disorders (odds ratio=2.01, 95%
      CI=1.04-3.87). Prevalence of depression, anxiety, cognitive, and sleep disorders
      were not dependent on receipt of post-surgical chemotherapy treatment. These
      findings support the need for heightened awareness for mental conditions
      following chemotherapy.

PMID- 16288132
TI  - Prevalence and correlates of illness worry in the general population.
AB  - The prevalence and correlates of illness worry in the general population were
      investigated in a representative sample. The authors screened residents of the
      United States by telephone, and more detailed interviews were conducted with 123
      respondents who reported at least 1 month of worry about serious illness in the
      past 12 months and an equal number of randomly selected persons without such
      worry. Data on demographic characteristics, medical and psychiatric conditions,
      functional impairment, and health care utilization were collected. At least 1
      month of worry was endorsed by 13.1% of the screened population. Correlates of
      worry included a cluster of psychiatric conditions (major depressive episode,
      panic attacks, and generalized anxiety disorder) and three clusters of physical
      conditions (heart disease, cancer, and other diseases). Worry about serious
      illness was associated with functional impairment and health care utilization.

PMID- 16288133
TI  - Somatoform disorders among first-time referrals to a neurology service.
AB  - Consecutive new neurology inpatients and outpatients (N=198) were assessed for
      somatoform disorders by using the Schedules for Clinical Assessment in
      Neuropsychiatry. Sixty-one percent of the patients (59% of the female patients
      and 63% of the male patients) had at least one medically unexplained symptom, and
      34.9% fulfilled the diagnostic criteria for an ICD-10 somatoform disorder (27.7%
      of the male patients, 41.3% of the female patients, 20.5% of the inpatients, and
      43.2% of the outpatients). The prevalence figures were about the same when DSM-IV
      criteria for somatoform disorders were used. Of the patients with a somatoform
      disorder, 60.5% also had another mental disorder. Somatization disorder,
      somatoform autonomic dysfunction, pain disorder, and neurasthenia were equally
      prevalent (6%-7%); dissociative (conversion) disorders and undifferentiated
      somatoform disorders were found in 2-3% of the patients. Fifty percent of the
      patients with somatoform disorders were identified by the neurologists.

PMID- 16288134
TI  - Nonpsychiatric medical treatment of body dysmorphic disorder.
AB  - Many individuals with body dysmorphic disorder seek nonpsychiatric medical and
      surgical treatment to improve perceived defects in their physical appearance.
      However, the types of treatments sought and received, as well as the treatment
      outcome, have received little investigation. This study describes the frequency,
      types, and outcomes of treatments sought and received by 200 individuals with
      body dysmorphic disorder. Treatment was sought by 71.0% and received by 64.0%.
      Dermatological treatment was most frequently sought and received (most often,
      topical acne agents), followed by surgery (most often, rhinoplasty). Twelve
      percent of the subjects received isotretinoin. Such treatment rarely improved
      body dysmorphic disorder. Thus, nonpsychiatric medical treatments do not appear
      effective in its treatment.

PMID- 16288135
TI  - Stress, social support, emotional regulation, and exacerbation of diffuse plaque
      psoriasis.
AB  - The authors' aim was to investigate the role of stressful events, perceived
      social support, attachment security, and alexithymia in triggering exacerbations
      of diffuse plaque psoriasis. Inpatients experiencing a recent exacerbation of
      diffuse plaque psoriasis (N=33) were compared with inpatients with skin
      conditions believed to have a negligible psychosomatic component (N=73).
      Stressful events during the last year were assessed with Paykel's Interview for
      Recent Life Events. Attachment style, alexithymia, and perceived social support
      were assessed with the Experiences in Close Relationships questionnaire, the
      Toronto Alexithymia Scale, and the Multidimensional Scale of Perceived Social
      Support, respectively. Multiple logistic regression analysis was used to control
      for age, gender, education, marital status, and alcohol consumption. In relation
      to comparison subjects, the patients with psoriasis had lower perceived social
      support and higher attachment-related avoidance. Also, they were more likely to
      have high alexithymic characteristics. There were no differences between the
      patients with psoriasis and the comparison subjects in scores on the Experiences
      in Close Relationships anxiety scale, the total number of stressful events, and
      the number of undesirable, uncontrollable, or major events. Although caution
      should be applied in generalizing these findings to outpatients, this study
      suggests that alexithymia, attachment-related avoidance, and poor social support
      might increase susceptibility to exacerbations of diffuse plaque psoriasis,
      possibly through impaired emotional regulation. Several physiological mechanisms
      involving the neuroendocrine and the immune system might mediate the interplay
      between stress, personality, and diffuse plaque psoriasis.

PMID- 16288136
TI  - Antidepressant and statin interactions: a review and case report of simvastatin
      and nefazodone-induced rhabdomyolysis and transaminitis.

PMID- 16288137
TI  - Paranoid delusions and cognitive impairment suggesting Fahr's disease.
AB  - The authors present the case of a 60-year-old woman with elaborate paranoid
      delusions and cognitive impairment found during a workup for atypical chest pain.
      Clinical evaluation revealed mild dementia, and radiography showed basal ganglia
      calcification consistent with Fahr's disease. She was treated with risperidone
      and transferred to a psychiatric inpatient unit for definitive care.
      Psychiatrists should consider Fahr's disease as a differential diagnosis in the
      evaluation of psychosis and cognitive impairment when neuroimaging reveals
      calcification of the basal ganglia.

PMID- 16288138
TI  - Predictors of HIV and hepatitis testing and related service utilization among
      individuals with serious mental illness.
AB  - Two hundred mentally ill adults receiving community-based outpatient psychiatric
      services were surveyed. Although 59% received an HIV test, only 41% received a
      hepatitis test. Clinic location and reports of unprotected sex were associated
      with receipt of an HIV test. Although no behavioral risk factors were associated
      with hepatitis testing, those with a comorbid medical condition were more likely
      to be tested. Only 15% of the sample was immunized against hepatitis B. Medical
      hospitalization was the only factor related to immunization. These results
      indicate an urgent need to improve access to HIV and hepatitis testing and
      related treatment.

PMID- 16288139
TI  - Modafinil as an alternative to methylphenidate as augmentation for depression
      treatment.

PMID- 16288141
TI  - [Development and application of a computerized nursing process program for
      orthopedic surgery inpatients-- NANDA, NOC, and NIC linkages].
AB  - PURPOSE: The purpose of this study was to develop and to apply the NANDA, NOC,
      and NIC (NNN) linkages into a computerized nursing process program using the
      classification systems of nursing diagnoses, nursing outcomes and nursing
      interventions. METHOD: The program was developed with planning, analysis, design
      and performance stages. The program was applied to 117 patients who were admitted
      to orthopedic surgery nursing units from January to February, 2004. RESULTS:
      Thirty-five of fifty-three nursing diagnoses were identified. Five nursing
      diagnoses in order of frequency were: Acute pain (28.4%), Impaired physical
      mobility (15.6%), Impaired walking (8.7%), Chronic pain (5.5%) and Risk for
      disuse syndrome (5.0%). The nursing outcomes of the 'Acute pain' nursing
      diagnosis tended to have higher frequencies (cumulative) in order of Pain
      management (95.2%), Comfort level (35.5%) and Pain level (17.7%). The nursing
      interventions of the 'Acute pain' nursing diagnosis tended to have higher
      frequencies (cumulative) in order of Pain management (71.0%), Splinting (24.2%)
      and Analgesic administration (17.7%). In comparison of outcome indicator scores
      between before and after the intervention according to the 61 nursing outcomes,
      the mean scores of 52 outcome indicators after the intervention were
      significantly higher than before the intervention. CONCLUSION: It is expected
      that this program will help nurses perform their nursing processes more
      efficiently.

PMID- 16288142
TI  - [A marital-relationship enhancement program for couples: randomized controlled
      trial].
AB  - PURPOSE: This paper reports a randomized controlled trial to investigate the
      effects of a Marital-relationship enhancement program(MREP) for marital couples.
      METHODS: Volunteer couples from several well-being centers in Seoul were randomly
      assigned either to a treatment group (n=36), participating in a MREP based on
      Gottman's "sound marital house" theory, or to a control group (n=35) receiving no
      treatment. The content of the MREP was provided to the control group after the
      research was completed. Data was collected from December 2003 to May 2004 using
      modified versions of the inventories developed by Gottman on marital
      satisfaction, positive affect, conflict regulation, and communication barriers.
      RESULTS: Participants in the experimental group showed significant improvements
      in marital satisfaction, positive affects, conflict regulation, and communication
      barrier scores compared to the control group. CONCLUSION: The present program for
      marital-relationship enhancement is helpful in enhancing marital relationships
      and regulating conflict between marital couples and, ultimately, may be useful to
      prevent divorce.

PMID- 16288143
TI  - [Emergency nurse-patient interaction behavior].
AB  - PURPOSE: The main purpose of this study was to explore nurse-patient interaction
      behaviors and patient satisfaction with the interaction in the emergency
      department. METHOD: This study used video technology to record complete
      conversations between the nurse and patient, thus obtaining the interactions
      naturally occurring in a clinical setting. The participants were 28 nurses and 63
      patients in the emergency department at one university hospital located in Seoul.
      The data was collected from November, 2002 to April, 2003. The video recordings
      were observed for 4 hours for each case and coded using an adapted version of
      Roter's Interaction Analysis System (RIAS), which yields frequencies of thirty
      six types of interaction behaviors. RESULT: The information exchange related to
      therapeutic items including medications, simple orientation, and situational
      positive talk were characterized in the nurses' interaction behaviors. Giving
      information about one's own condition, questions about therapeutic regimen, and
      showing worry were characterized in patient interaction behaviors. The patients'
      satisfaction with the interaction was 37.75.9 (range 9-45). CONCLUSION: The
      emergency nurse-patient interaction behavior was task-related. The results
      suggest that identification of effective interaction behavior in the Emergency
      department and an interaction skill training program could increase patient
      satisfaction.

PMID- 16288144
TI  - [Effects of auricular acupuncture on insomnia in Korean elderly].
AB  - PURPOSE: This study was to examine the effects of auricular acupuncture on
      insomnia in Korean elderly. METHOD: The study design was a triangulation study.
      Subjects were 40 elderly who were 65 years and over in Seoul, and 10 subjects for
      a qualitive study who were saturated with interviews and observation. The first
      auricular acupuncture was applied for three days, and this was applied to
      subjects on a 5 times series. The quantative data was analyzed by SPSS PC+ and
      the qualitive data was analyzed by driving of core meaning and abstract concepts
      using a semi-structural interview and observation. RESULT: 1. The experimental
      group had higher significant sleep scores than that of the control group
      (t=32.739, p=.001). 2. The experimental group had higher significant self-
      satisfaction scores on sleep than that of the control group (t=30.049, p=.001).
      3. In the qualitive study, insomnia characteristics before application of
      auricular acupressure therapy were confirmed by physical dysfunction, recall of
      past, and psychological dysfunction. Insomnia characteristics after application
      of auricular acupressure therapy were confirmed by recovery of physical
      dysfunction, improving recall of past, and recovery of psychological dysfunction.
      CONCLUSION: Auricular acupuncture was effective on insomnia in Korean elderly.

PMID- 16288146
TI  - [Development and evaluation of a vital signs e-book for undergraduate student
      nurses].
AB  - PURPOSE: The purpose of this study was to develop a vital signs e-book for
      undergraduate student nurses and evaluate the content, system and student
      satisfaction. METHOD: This study was done in three stages, the development of a
      vital signs e-book, implementation and evaluation. The subjects were 73
      undergraduate student nurses in Y university. RESULT: Thirty one learning
      objectives were used to create the contents. A set of 5 chapters and 18
      subsections were defined after validation from nurse educators. The e-book is
      available at http://123.134.207.23/ebook/vitalsigns. Analysis of the
      questionnaires showed a mean score for content, system and students satisfaction
      of 3.17 +/- .73, 3.11 +/-.79, and 2.96 +/-.74 respectively out of a possible 4
      points. CONCLUSION: Nurse educators should provide quality and effective web
      based courses that meet undergraduate student nurses' learning needs and they
      should incorporate web-based learning into traditional teaching to meet the
      demands of nursing education.

PMID- 16288145
TI  - [The experiences of recovery from disease in patients doing meditation].
AB  - PURPOSE: The purpose of this study was to explore the experiences of recovery
      from disease in the patients doing a kind of Buddhist meditation, and to develop
      a grounded theory about meditation. METHOD: Data was collected by an in-depth
      interview using tape-recordings from sixteen participants doing meditation. The
      data was analyzed using the grounded theory method proposed by Strauss and
      Corbin(1998). RESULT: The core category was discovering the true self. The
      participants began to do meditation because of their disease. They experienced
      obstacles due to incomplete religious acceptance. However, their faith grew
      gradually based on religious experiences that were indescribable. Finally, they
      entirely trusted the inner healer, which is emphasized in meditation. The
      strategies that they used were self reflection and seeking help for accepting
      deep meditation. They were stabilized in physical, psychological and social daily
      living. The processes of discovering the true self were identified as entering
      religious discipline, embodying religious discipline, self-accomplishing
      religious faith, and recovering mind-body health. CONCLUSION: This study provided
      the understanding of mind-body integration. Empirical research may be needed to
      prove scientifically the effects of meditation.

PMID- 16288147
TI  - [Effects of a maternal education program based on the temperament theory on the
      temperamental goodness-of-fit between mother and child].
AB  - PURPOSE: This study was aimed to evaluate the effects of a maternal education
      program based on the temperament theory on the temperamental goodness-of-fit
      between mother and child. METHOD: The research method was a nonequivalent,
      control group, non-synchronized design and the experimental period was from May
      10, 2004 to July 24, 2004. The subjects were mothers who had children 3-4 years
      old who registered in eight kindergartens or infant schools in M city. Among the
      total 94 subjects, 47 were allocated as an experimental group and 47 were a
      control group. Using the SPSS/WIN 10.0 program, the data was analyzed by a Chi
      square test, and t-test. RESULT: 1. After treatment with a maternal education
      program based on the temperament theory, the experimental group significantly
      decreased in scores for perceived children's behavior problems in comparison to
      the control group(t=-4.01, p<.001). 2. After treatment with a maternal education
      program based on the temperament theory, the experimental group did not
      significantly decrease in scores for parenting stress in comparison to the
      control group(t=-.85, p=.40). 3. After treatment with a maternal education
      program based on the temperament theory, the experimental group did not
      significantly decrease in scores for rejective parenting behaviors in comparison
      to the control group(t=-1.32, p=.19). CONCLUSION: A maternal education program
      based on the temperament theory is a useful intervention to decrease perceived
      children's behavior problems.

PMID- 16288148
TI  - [The effects of a health promotion program for elderly].
AB  - PURPOSE: The purpose of this study was to develop and to evaluate a health
      promotion program for elderly. METHOD: Subjects were 63 elderly women
      (experimental group: 33, control group: 30). The study was a nonequivalent
      control group pretest-posttest design. The data was analyzed with an SPSS Window
      program, then the data was computed for the purpose of each study. RESULT: 1. In
      designing the program, the experimental group was given health education--2 times
      per week, for 8 weeks--and they participated in recreation programs and
      stretching exercises five times a week. 2. Stretching exercises including health
      education, significantly affected the total Cholesterol, HDL-cholesterol,
      triglycerides, health behavior and self-efficacy. 3. The body fat weight was not
      significantly affected by the stretching exercises. CONCLUSION: This program was
      tested to promote the health of elderly and verified as an effective nursing
      intervention program, because the outcome of this program ascertains that this
      program enhances self efficacy of exercise, reduces Cholesterol and triglyceride
      levels' increases HDL-cholesterol, and helps promote the understanding of heath
      behavior.

PMID- 16288149
TI  - [Validity and reliability of an instrument for predictive nursing intention for
      SARS patient care].
AB  - PURPOSE: This study was done to develop and test validity and reliability of on
      instrument for predicting nursing intention for SARS patient care. METHOD: The
      psychometric properties of a SARS patient care attrition prediction tool, based
      on the Theory of Planned Behavior, were examined in this study. The Three-phase
      design involved a) salient beliefs generated from clinical nurses (n=43) b)
      content validation by expert panel evaluations(n=5) c) face validation by plot
      testing (n=10) d) and instrument validation in a cross sectional survey (n=299).
      Psychometric analysis of survey data provided empirical evidence of the construct
      validity and reliability of the instrument. RESULT: Principal component analysis
      verified the hypothesized 6-factor solution, explaining 68.2% of variance, and
      Alpha coefficients of .7538 to .9389 indicated a high internal consistency of the
      instrument. CONCLUSION: The instrument can be used by nurse administrators and
      researcher to assess clinical nurses' salient beliefs about caring for SARS
      patients, guide tailored intervention strategies to effective caring, and
      evaluate the effectiveness of interventions.

PMID- 16288150
TI  - [Testing reliability and validity of reduced substitutes for leadership scales(rd
      SLS)].
AB  - PURPOSE: This paper was conducted to test the reliability and validity of rd-SLS,
      developed by Podsakoff, et al. (1993) which measured 'substitutes for
      leadership'. METHOD: The subjects were 345 nurses in 5 general hospitals.
      Cronbach's and the Guttman split-half coefficient were used to test the
      reliability of rd-SLS. Factor analysis, and the correlations of the rv-SLS and
      SLS with rd-SLS were used for convergent and discriminant validity. RESULT:
      Cronbach's data was 0.76 and the Guttman split-half coefficient was 0.52. Twelve
      factors evolved by factor analysis, which explained 70.4% of the total variance.
      This result was similar to previous study results. However, 'Indifference toward
      organizational rewards'-related items were classified two factors. It was not
      clear t hat the rd-SLS consisted of 13 concepts(factors). The correlations of the
      rv-SLS and SLS with the rd-SLS were 0.93 and 0.87 respectively. CONCLUSION: The
      rd-SLS showed a moderate degree of validity and reliability. Thus, it is
      recommended to use the rd-SLS in general nursing organizations for screening for
      leadership substitutes. In addition, it is necessary to clarify the concept of
      organizational rewards. In a further study, the factor structure of the rd-SLS
      may be considered.

PMID- 16288151
TI  - [Evaluation of a self-efficacy-based basic life support program for high-risk
      patients' family caregivers].
AB  - PURPOSE: The purpose of this study was to evaluate a Self-efficacy-based Basic
      Life Support (SEBLS) program for high-risk patients' family caregivers on cardiac
      arrest. The SEBLS program was constructed on the basis of Bandura's self-efficacy
      resources as well as the International Liaison Committee on Resuscitation's "2000
      Guidelines for CPR and ECC". METHOD: The effect of the SEBLS program on emergency
      response self-efficacy and emergency response behavior such as BLS (Basic Life
      Support) knowledge and BLS skill performance was measured by a simulated control
      group pretest-posttest design. Study subjects were38 high-risk patients' family
      caregivers (20 experimental subjects and 18 control subjects) whose family
      patients were admitted to a general hospital in Incheon, Korea. RESULT: 1.
      Emergency response self-efficacy was significantly higher in the experimental
      subjects who participated in the SEBLS program than in the control subjects.
      (t=8.3102, p=0.0001). 2. For emergency response behavior, BLS knowledge
      (t=5.6941, p=0.0001) and BLS skill performance (t=27.8281, p=0.0001) was
      significantly higher in experimental subjects than in control subjects.
      CONCLUSION: A SEBLS program can increase emergency response self-efficacy and
      emergency response behavior, and could be an effective intervention for high-risk
      patient's family caregivers. Long-term additional studies are needed to determine
      the lasting effects of the program.

PMID- 16288152
TI  - [Development of a nursing professional values scale].
AB  - PURPOSE: The purpose of this study was to develop an instrument to measure
      nursing professional values. METHOD: Forty preliminary items were selected by
      classifying 223 basic items extracted via a literature study and in-depth
      interviews of subjects and testing the relevance of their contents. In order to
      verify the reliability and relevance of the preliminary instrument, data was
      collected from 504 nurses in 3 general hospitals. RESULT: As a result of the item
      analysis, 29 items were selected from a total of 40 items. Five factors were
      extracted by factor analysis, and the total variance was 51.5%. For the
      explanation of variances by factors, the 1st factor, 'self-concept of the
      profession' accounted for 14.8%, the 2nd factor, 'social awareness' 12.1%, the
      3rd factor, 'professionalism of nursing' 9.8%, the 4th factor, 'the roles of
      nursing service' 9.1%, and the 5th factor, 'originality of nursing', 5.6%.
      Cronbach's Alpha of those 29 items was .9168, which was high. CONCLUSION: This
      paper is meaningful in a way that it developed a tool capable of measuring
      nursing professional values, which reflects the characteristics of our country.
      In order to re-verify the relevance and stability of this tool, it is necessary
      that comparative studies should be conducted.

PMID- 16288153
TI  - [A review of exercise interventions for fall prevention in the elderly].
AB  - PURPOSE: This study was done to suggest directions for developing exercise
      interventions for fall prevention in the elderly in Korea in the future. METHOD:
      Twenty five articles for fall prevention exercises were reviewed and analyzed.
      RESULT: 84.0% of subjects were older adults age 65 and older living in the
      community. The most frequently performed interventions were lower limb strength
      and balance exercises together 43.3%, group exercise 70.0%, exercise 3 times/week
      60.0%, 60 min per session 36.7%, duration of 12 weeks and 1 year 23.3% each. The
      most frequently used outcome variables were static balance 84.0%, lower limb
      muscle strength 72.0%, dynamic balance 56.0 %, and falls 56.0 %. The effect of
      exercise interventions on fall prevention was inconclusive. Lower limb strength
      exercises with resistance were effective for increasing muscle strength. Balance
      exercises with various movements for balance were effective for increasing
      balance. CONCLUSION: Exercise interventions for fall prevention is recommended
      for older adults with risk factors of falling. The desirable type of exercise
      intervention is lower limb strength and balance exercise together.

PMID- 16288154
TI  - [Development of an e-learning program about medication for new nurses].
AB  - PURPOSE: The purpose of this study was to develop an e-Learning program about
      medication for nurses to enhance nurses' medication performance ability and to
      analyze learners' responses after studying with this program. METHOD: For the
      development of the e-Learning program, the NBISD(Network Based Instructional
      Systems Design) model, suggested by Jung(1999) was applied as a basic model and
      the instruction design theory of Gagne & Briggs(1979) and ARCS theory of
      Keller(1983) were applied. After the operation of this program for one month to
      34 new nurses, learners' responses were analyzed. RESULT: Learners' knowledge of
      medication was greatly improved after this program. In addition learners'
      satisfaction with the overall education program, help in field applicability,
      ease of screen shift and exploration, and tutor activities were high and the
      contents were regarded suitable for e-Learning. Many things were advantageous
      such as easy accessibility, easy understandability with pictures and flash
      animation, practical cases and feedback from a tutor. Provision of a
      supplementary handout and improvement of a tight time schedule were pointed out
      as things to be improved. CONCLUSION: This e-Learning program can be used
      effectively for medication education for registered nurses, student nurses, and
      new nurses.

PMID- 16288155
TI  - [The daily experiences of people with chronic schizophrenia].
AB  - PURPOSE: This research investigated the daily experiences of patients' lives to
      develop a formal theory that explains the lives of schizophrenic patients.
      METHOD: A grounded theory method(Strauss & Corbin, 1998) guided the data
      collection and analysis. Thirteen patients who were diagnosed with schizophrenia
      in regional communities participated. RESULT: The experiences of chronic
      schizophrenic patients are defined as "escaping from a fallen mine" comparing
      their suffering to that of entrapped miners trying to free themselves from a
      collapsed mine tunnel with much difficulty and without hope. In observing
      participant's time lines of having lived with chronic schizophrenia, it advances
      with "surrender", "collapse", "reaching out", "rising", "preparing to spring up",
      and "starting anew". CONCLUSION: The results of this study indicate that the
      experience of a chronic schizophrenic patient is like that of a miner caught
      under a fallen mine channel, who, without external help cannot escape the depths
      of the mine, but at the same time must have conviction and hope of rescue and
      avert fear to cooperate with outside help. The result indicates that family
      members, doctors and nurses as well as an institute's persistent and active
      support is most critical for the patient's adjustment to social life.

PMID- 16288156
TI  - [A comparison of perceived nursing needs among oncology nurses, patients with non
      terminal cancer and patients with terminal cancer].
AB  - PURPOSE: The purpose of this study was to compare the perceived importance and
      the perceived caring of nursing needs among oncology nurses, patients with non
      terminal cancer and patients with terminal cancer. METHOD: A total of 83 oncology
      nurses, 56 patients with non-terminal cancer and 39 patients with terminal cancer
      served as subjects. Data was collected based on the 4-point Likert scale using a
      self-administered questionnaire from Mar. to Sept. 2004. Finally, data was
      analyzed using mean, SD, paired-test, and ANOVA. RESULTS: The score of the
      perceived importance of nursing needs was higher than that of the perceived
      performance of nursing needs in all three groups. There was also a difference in
      the degree of perceived performance of nursing needs among the three groups. In
      contrast, there was no difference in the total score of the perceived importance
      of nursing needs among the three groups, unlike the importance of informational
      and physical needs as a subgroup of perceived importance, where a difference was
      noted. CONCLUSIONS: Strategies should be developed to narrow down these gaps
      between nurses and patients. In particular, informational and educational
      programs should be designed for patients with terminal cancer.

PMID- 16288157
TI  - [The effects of exercise program on knowledge and attitude of exercise and
      depression in low-income elderly women].
AB  - PURPOSE: The purpose of this research was to examine the effects of exercise
      program on knowledge and attitude of exercise, and depression in low-income
      elderly women. METHOD: The research design was a nonequivalent control group
      pretest-posttest design. The subjects were 26 in the experimental group and 22 in
      the control group among 46 low-income women over age 65. The independent variable
      is the exercise program, and the dependent variables are knowledge and attitude
      of exercise and depression. The exercise program was performed for 45-50 minutes,
      twice a week for 8 weeks. Data was collected from March 12. to May 8. 2004.
      RESULT: Participants were given a pre-test and post-test for the selected
      variables. The experimental group reported significant improvements in their
      knowledge and attitude of exercise and depression scores compared with the
      control group. CONCLUSION: The results indicated that the exercise program had
      the potential to manage low-income elderly women's health promotion. Furthermore,
      the exercise program can enhance life satisfaction in low-income elderly women.

PMID- 16288158
TI  - [The effects of a folk play program on cognition, ADL, and problematic behavior
      in the elderly with dementia].
AB  - PURPOSE: This study was to develop and evaluate a folk play program as a nursing
      intervention for the elderly with dementia. METHOD: First, a folk play program
      was developed through a careful study of literature review and field-work.
      Second, a nonequivalent control group pre-post test was designed. The subjects of
      the study were the elderly with dementia staying in nursing homes; 15 were in an
      experimental group adopting a folk play program developed through this study, 18
      in the control group on a gymnastics and walking program which is generally used.
      The 40 min. intervention was conducted 5 times a week for 4 weeks. RESULT: The
      folk play program improved the cognition(t=6.12, p<.001) and ADL(t=2.92, p=.014)
      and diminished the frequency of problematic behaviors significantly(t=-6.39,
      p<.001). There was a significant difference of cognition, ADL, and problematic
      behaviors between the control and the experimental group before and after the
      experiment(t=3.38, p=.002; t=2.05, p=.046; t=-7.74, p<.001). CONCLUSION: Compared
      with the gymnastics and walking program, the folk play program proved to be much
      more effective in the elderly with dementia in improving their cognition and ADL,
      as well as in diminishing their problematic behaviors. Therefore, a folk play
      program should be applied as an effective and practical Korean nursing
      intervention for the elderly with dementia.

PMID- 16288159
TI  - [Changes in smokers' perception about smoking before and after participation in a
      hospitalized smoking cessation program].
AB  - PURPOSE: This study was done to analyze the changes in smokers' subjectivity
      about smoking before and after participation in a 5-day hospitalized smoking
      cessation program. DESIGN: Q-methodology, which provides a scientific method on
      subjectivity, was applied. FINDINGS: Nine types of subjectivity changes about
      smoking were identified; Type I, Nicotine craving --> Confident of self control
      for smoking; Type II, Nicotine craving --> Cognition of the link between
      habituation and smoking, Type III, Nicotine craving --> Nicotine craving, Type
      IV, smoking as a social behavior --> Cognition of the link between habituation
      and smoking, Type V, smoking as a social behavior --> Motive to turn away from
      being addicted to smoking to being healthy, Type VI, Habitual smoking -->
      Confident of self control for smoking, Type VII, Habitual smoking --> Cognition
      of the link between habituation and smoking, Type VIII, Habitual smoking -->
      Motive to turn away from being addicted to smoking to being healthy and Type IX,
      Denial of the negative effects of smoking --> Confident of self control for
      smoking. CONCLUSION: The types of changes in smokers' subjectivity before and
      after the smoking cessation program in this study suggest a better tailored
      intervention for individual smokers. The types of changes on smokers'
      subjectivity provide insight about which factors of the interventions for smoking
      cessation are especially valued for a particular group of smokers.

PMID- 16288160
TI  - [Adjustment after a hysterectomy].
AB  - PURPOSE: This study examined the relationship between sexual changes and
      adjustment and identified the factors which affect adjustment after a
      hysterectomy. METHOD: The subjects were 89 women under 50 years of age registered
      at gynecology departments of general hospitals in Seoul. RESULT: 60.7% of the
      women restarted coitus during six weeks to three months post operation. They felt
      a decrease in vaginal secretions (68%), and abdominal and pelvic pain (59.8%),
      but 2/3 of them didn't change the frequency of coitus and level of orgasm. With
      respect to the adaptability of the sexual life, there was a significant
      difference in the time to restart coitus, lack of vaginal secretions, abdominal
      and pelvic pain, change of frequency of coitus, experience of orgasm, importance
      of sex and avoidance of coitus, according to job, income, and health condition.
      CONCLUSION: It is appropriate to restart coitus six weeks to three months after
      surgery and preliminary information should be given to patients after surgery as
      abdominal and pelvic pain could be relieved after twelve months. Also, sexual
      adjustment can be improved if they can recognize the changes after surgery from
      sexual life before surgery.

PMID- 16288161
TI  - [Factors influencing headache in children].
AB  - OBJECTIVES: This descriptive study was conducted to examine the degree of stress,
      coping styles, communication with the mother and depression between headache
      suffering children and headache-free children and to explore predicted factors
      for headache occurrence in children. METHOD: The subjects of this study consisted
      of 196 headache-free children and 107 headache-suffering children. They were 4th
      6th graders of an elementary school in T city. The instruments in this study were
      David's stressor of children, Lazarus & Folkman's Stress Coping Style, PACI
      (Parent-Adolescent Communication Inventory) by Barnes & Olsen and Kovac's CDI
      (Children's depression inventory). Data were collected from May 2 to July 16,
      2004. RESULTS: Total stress (t=-3.76, p=.035), school stress (t=-3.02, p=.001),
      mass media stress (t=-1.39, p=.029) and depression (t=7.62, p=.001) in headache
      suffering children were significantly higher than those of headache-free
      children. Problem-oriented coping skills (t=1.23, p=.023), and the score of
      communication with the mother (t=2.32, p=.012) in headache-suffering children
      were lower than those of headache-free children. Logistic regression analysis
      (stepwise) showed that the most powerful predictor was stressors in school,
      followed by depression, stressors in mass media and communication with the
      mother. CONCLUSIONS: This study revealed that important factors such as the
      degree of school stress, depression, the degree of mass media stress,
      communication with the mother and problem-oriented coping skills should be
      controlled for reducing of headaches in children.

PMID- 16288163
TI  - Diagnostic imaging in Canada.
AB  - In Ontario, between 1993 and 2003, the annual number of MRI scans performed
      increased by more than 600 percent (Iron et al. 2003), and the number of CT scans
      increased threefold (Tu et al. 2005). Despite these massive increases, the Fraser
      Institute reported a median wait of five weeks for CT and thirteen weeks for MRI
      scanning in 2004 (Esmail and Walker 2004), and Canadians are increasingly
      concerned about the length of time they wait for diagnostic imaging. Because of
      this, politicians have made decreasing wait times for diagnostic imaging one of
      their top priorities (Health Canada 2004). This raises several interesting
      questions. Have the indications for CT and MRI really expanded that rapidly, or
      was there just a huge pent-up demand because Canada had fallen so far behind in
      acquiring modern imaging machines? Are physicians relying more on diagnostic
      imaging technologies and less on clinical skills? Are an increasing number of
      patients undergoing scans when there is a small likelihood that the results will
      change their management or improve their outcomes? Supporters of the view that
      Canada needs to expand its diagnostic imaging capacity point to the fact that we
      rank well behind many developed countries in terms of the number of diagnostic
      imaging machines per population (Canadian Institute for Health Information 2003:
      33), and that improvements in imaging quality have expanded the indication for
      imaging. Supporters of the view that there is an increased and inappropriate
      reliance on technology over clinical skill point to the findings of a recent
      American study showing that the regions that spent the most on healthcare did not
      have better outcomes than the regions that spent less--indeed, the trend was
      toward poorer outcomes in the highest-spending regions (Fisher et al. 2003a,
      2003b). One of the greatest differences between the highest- and lowest-spending
      regions was their expenditure on a variety of diagnostic tests, suggesting that
      more testing did not lead to better outcomes on a population basis. It may in
      fact have led to iatrogenic illnesses because of the workup of false positive
      results, and diverted attention away from simple interventions that have been
      shown to be effective (Fisher et al. 2003a). The truth is likely a combination of
      many factors. Some patients with clear indications for diagnostic imaging
      undoubtedly wait too long for their tests in Canada. At the same time, a number
      of patients undergo tests whose results have a very small likelihood of changing
      their management, which itself contributes to the access problem. Unfortunately
      there are no evidence-based benchmarks for the appropriate rate of diagnostic
      testing that can be used to determine the optimal supply of diagnostic machines
      and radiological personnel. In this article we discuss the reasons it has been so
      difficult to determine the optimal imaging capacity needed for a population,
      describe some factors that are "inappropriately" increasing the rate of imaging
      and suggest some solutions. Although many of our examples deal with CT and MRI
      scanning, our remarks apply more broadly to many other diagnostic tests.

PMID- 16288164
TI  - Making the best use of radiological resources in Canada.
AB  - Diagnostic imaging plays a crucial frontline role in healthcare, providing the
      information some physicians need to make a diagnosis and determine a course of
      treatment for their patients. However, wait times for access to diagnostic
      imaging examinations continue to be long. This is due to a number of factors,
      including the expanding indications for CT and MRI and growing reliance on
      imaging studies, Canada's lag in purchasing new equipment, an American influence
      on the Canadian healthcare system and clinicians' requests for inappropriate
      examinations. A number of strategies need to be implemented to maximize
      radiology's efficiency and ensure that services are being used appropriately. The
      author advocates the use of appropriateness guidelines for referring physicians,
      delisting tests that are completely inappropriate, implementing the use of
      radiology information systems, enhancing radiologist efficiency and using
      physician extenders to perform less complex medical work.

PMID- 16288165
TI  - Further reflections on diagnostic imaging in Canada.
AB  - Diagnostic imaging in Canada requires careful rethinking, retooling and
      innovative management. Much of the attention directed to diagnostic imaging
      services has focused on cost containment and most of this on supply-side
      management. These "reflections" reinforce and supplement the perspectives offered
      by Drs. Laupacis and Evans and extend considerations around demand-side
      management, from the perspectives of physician and patient. Focusing on
      physicians makes sense, since, in the end, they are the ones who order diagnostic
      imaging tests. Multidimensional reinforcing modalities are required to sustain
      changes in physician test-ordering behaviour. This should be combined with peer
      review and audit, clinical guidelines and a consultant role for radiologists, as
      described by Laupacis and Evans. Educating patients about risk, cost and
      appropriateness of diagnostic imaging tests is of supplementary importance.

PMID- 16288166
TI  - The burgeoning disorder of technophilia.
AB  - Andreas Laupacis and William Evans have deftly accomplished the difficult task of
      synthesizing the major issues at hand. Their comments are timely, reflecting
      society's increasing preoccupation with rapid access to diagnostic imaging.
      Paradoxically, the recent CIHI report on medical imaging records a steady
      increase in scanners, without the expected reduction in wait times. The role of
      private facilities is unclear, and the value of screening asymptomatic patients
      is unproven. There are few clear guidelines for ordering images. New
      intraoperative, functional and molecular imaging technologies will further strain
      the system. This array of challenges should be urgently tackled by a decisive
      panel of national experts, who would in turn supervise consultants working full
      time on guideline development.

PMID- 16288167
TI  - The power of technology: resisting the seduction through rationality?

PMID- 16288169
TI  - [Pathophysiological mechanisms implicated by high-frequency stimulation in
      Parkinson's disease: the restoration of high and low frequency oscillatory
      systems].
AB  - INTRODUCTION: Increased neuronal activity in the internal pallidum (GPi) and the
      subthalamic nucleus (STN) has been clearly demonstrated in Parkinsonian models,
      and the two structures have thus been selected as therapeutic targets for
      functional neurosurgery. High-frequency electrical stimulation of the GPi or the
      STN improves the parkinsonian symptoms but also dyskinesias directly by GPi
      stimulation or indirectly by reduction of L-Dopa associated with STN stimulation.
      According to Alexander's model of the organisation of the basal ganglia,
      electrical stimulation of GPi or STN should have led to uncontrolled
      hyperkinesia. This apparent paradox could be explained on one hand by the
      involvement of different anatomo-functional areas within these structures and on
      the other by spatial and temporal changes in neuronal discharge patterns in the
      basal ganglia which in turn produce variations in synchronisation. RESULTS: Event
      related (de)synchronisation (ERD) has enabled us to study variations in
      subcortico-cortical oscillatory activity: it has been shown that high-frequency
      electrical stimulation of the GPi/STN increases desynchronisation of low
      frequency rhythms (mu and beta,<30 Hz) during movement preparation and execution
      and augments post-movement synchronisation. Stimulation also decreases the
      abnormal frontocentral spreading of desynchronisation during movement
      preparation. CONCLUSIONS: In accordance with previous coherence analyses,
      electrical stimulation of STN is likely to restore the activity of high-frequency
      and low-frequency systems, as evidenced by a decrease in the hypersynchronisation
      of low-frequency rhythms at rest and restoral of a high-frequency rhythm during
      movement. Stimulation may improve spatial selectivity by activating the selected
      programs in conjunction with the primary sensorimotor cortex, whilst inhibiting
      competitive programs represented by abnormal spreading outside the primary
      sensorimotor cortex.

PMID- 16288170
TI  - [Peripheral nerve repair: 30 centuries of scientific research].
AB  - INTRODUCTION: Nerve injury compromises sensory and motor functions. Techniques of
      peripheral nerve repair are based on our knowledge regarding regeneration.
      Microsurgical techniques introduced in the late 1950s and widely developed for
      the past 20 years have improved repairs. However, functional recovery following a
      peripheral mixed nerve injury is still incomplete. STATE OF ART: Good motor and
      sensory function after nerve injury depends on the reinnervation of the motor end
      plates and sensory receptors. Nerve regeneration does not begin if the cell body
      has not survived the initial injury or if it is unable to initiate regeneration.
      The regenerated axons must reach and reinnervate the appropriate target end
      organs in a timely fashion. Recovery of motor function requires a critical number
      of motor axons reinnervating the muscle fibers. Sensory recovery is possible if
      the delay in reinnervation is short. Many additional factors influence the
      success of nerve repair or reconstruction. The timing of the repair, the level of
      injury, the extent of the zone of injury, the technical skill of the surgeon, and
      the method of repair and reconstruction contribute to the functional outcome
      after nerve injury. CONCLUSION: This review presents the recent advances in
      understanding of neural regeneration and their application to the management of
      primary repairs and nerve gaps.

PMID- 16288171
TI  - [Psychiatric comorbidity in patients with pseudoseizures: retrospective study
      conducted in a video-EEG center].
AB  - INTRODUCTION: Pseudoseizures involve a group of paroxysmal behavioral symptoms
      mimicking an epileptic seizure, but without modifications of cerebral electrical
      activity. PATIENTS AND METHOD: In this retrospective study focusing on mental
      disorders, 37 patients with pseudoseizures were recorded during video-EEG
      procedure. RESULTS: According to DSM-IV criteria, 70 percent of the patients had
      at least one mental disorder when evaluated. Diagnoses were, in decreasing order
      of frequency: post-traumatic stress disorders, other anxious disorders,
      somatoform disorders, dissociative disorders, and mood disorders. CONCLUSION: The
      strong association between pseudoseizures and post-traumatic stress disorders is
      discussed. Our results argue in favor of a systematic evaluation of psychiatric
      comorbidity.

PMID- 16288172
TI  - [Preliminary pilot study of cyproterone acetate for the treatment of aggressive
      behavior associated with severe dementia].
AB  - INTRODUCTION: Behavioral symptoms are common in dementia, and seem to be more
      frequent in men than in women. Agitation is frequently responsible for caregiver
      burn-out and leads to institutionalization. The dramatic increase in the
      prevalence of Alzheimer's disease and related disorders requires better
      management of behavior symptoms. Although environmental adaptation has been
      proposed recently, for many years, psychoactive medications and physical
      restraints were the primary approach. However, in severely demented patients,
      both pharmacologic and non-pharmacologic treatments are inoperative. In this
      situation, alternative pharmacologic approach should be tested. Cyproterone
      acetate, an antiandrogen and progestative steroid has never been proposed to
      prevent aggressive behavior in dementia, but its favorable effect is well
      described in rat and monkey aggressivity. PATIENTS AND METHODS: Cyproterone
      acetate was proposed for 19 demented patients who developed severe aggressive
      behaviors or an agitation unresponsive to psychoactive drugs (even in
      association) or to environmental adaptation. Clinical and behavioral analysis was
      carried out using the Cohen-Mansfield agitation inventory associated with an
      assessment of dependency in daily life activities, before and during treatment
      with cyproterone acetate. The behavioral status was stable, with permanent or
      repetitive agitation. Seven patients had vascular dementia, 7 had Alzheimer's
      disease, 2 had fronto-temporal degeneration, 2 had Huntington's disease and 1 a
      probable diffuse Lewy bodies disease. Fifteen patients had prominent aggressive
      behavior and 4 had predominant aberrant motor behavior with aggressive behavior.
      RESULTS: Cyproterone (50 to 100mg - mean: 92.5mg daily) improved significantly
      aggressive and impulsive behavior related to Alzheimer's disease or vascular
      dementia but had no effect on aberrant motor behavior. When cyproterone was
      stopped, aggressive behaviors reappeared more rapidly in vascular dementia.
      CONCLUSION: Cyproterone acetate is then an interesting choice when aggressive
      behavior is not improved with psychotropic drugs. A detailed clinical analysis is
      required to avoid the use of cyproterone in non-aggressive and non-impulsive
      patients. The results of this preliminary study suggest a randomized double-blind
      study should be carried out in the near future. The behavior improvement could be
      related to the blockage of androgen receptors, and simultaneously to the sedative
      effect of progestative drugs.

PMID- 16288173
TI  - [Vogt-Koyanagi-Harada syndrome].
AB  - INTRODUCTION: Vogt-Koyanagi-Harada syndrome is a rare, inflammatory disease with
      manifestations affecting the ocular, central nervous, audito-vestibular, and
      integumentary systems. Vogt-Koyanagi-Harada syndrome is more frequent in Asia but
      is also described in Europe. We report three new non asiatic cases of this
      syndrome. OBSERVATIONS: The three patients had bilateral panuveitis and
      hypoacusia. Two of them had peripheral facial palsy, two of them had vestibular
      syndrome and one of them lymphocytic meningitis. In each case we found
      characteristic HLA II typing and in one case we discovered the simultaneous
      presence of three auto-antibodies: anti-retina (anti-Arrestin type), anti-choroid
      and anti-cochlea. These patients were treated by corticosteroids but required an
      additional treatment by cyclophosphamide (0.8g/m2). The clinical course was
      favorable with visual sequelae for two and auditory one for one. DISCUSSION:
      These biological and therapeutic elements and a review of the recent literature
      are in favor of an autoimmune origin of this syndrome.

PMID- 16288174
TI  - [A report of 9 cases of neurosarcoidosis].
AB  - INTRODUCTION: Neurological involvement in sarcoidosis is rare and highly
      variable. To date, no consensus was reached about the diagnosis approach. We
      report a case series of 9 patients with neuosarcoidosis, with favorable outcome
      under therapy. MATERIALS AND METHODS: We examined a case series of 9 patients
      with neurosarcoidosis. Clinical, radiological, therapeutic features and outcome
      were studied. RESULTS: Six of the nine patients were females. Patients' age
      ranged from 31 to 70 years. Initial neurological symptoms lead to the diagnosis
      of systemic sarcoidosis in all patients. Central nervous system involvement was
      found in 77 percent with cranial nerve involvement in 55 percent. Twenty-three
      percent of patients presented with peripheral neuropathy and 33 percent with
      meningitis. The diagnosis was definite in 2 patients, probable in one and
      possible in six others. All patients were given steroid therapy. Total remission
      was obtained in three and partial remission in three. Three patients remained
      stable and one died. CONCLUSION: Histological signs are not constant in
      neurosarcoidosis. The lack of these signs should lead the physician to search for
      latent extraneurological symptoms which are suggestive of the diagnosis. Nervous
      biopsy can thus be avoided.

PMID- 16288175
TI  - [Pseudomigraine with transient neurological deficits and cerebrospinal fluid
      lymphocytosis].
AB  - INTRODUCTION: Pseudomigraine with temporary neurological symptoms and lymphocytic
      pleocytosis is a rare syndrome resolving within less than 3 months. CASE REPORT:
      A young 17-year-old woman without previous medical history was admitted to the
      hospital because of right motor weakness and language disturbances. The symptoms
      resolved in a few hours and were followed by severe left headaches with important
      vegetative signs. Several similar episodes were noted in the previous 10 days.
      Cranial MRI was normal. EEG showed important slowing of the cerebral
      electrogenesis. More than 250 lymphocytic cells were found at CSF analysis.
      Outcome was spontaneously favorable, without similar symptoms after 6-month
      follow-up. CONCLUSION: Pseudomigraine with lymphocytic pleocytosis seems to be a
      particular syndrome of unknown origin. This is an elimination diagnosis,
      generally with a benign course.

PMID- 16288176
TI  - [Leflunomide-related severe axonal neuropathy].
AB  - INTRODUCTION: Leflunomide is a new drug for the treatment of rheumatoid
      arthritis. Its mechanism of action is based on lymphocyte inhibition. We report
      the cases of two patients treated with leflunomide who developed severe sensory
      motor axonal polyneuropathy. OBSERVATION: Two women (61- and 70-year-old)
      presented with a sensory-motor axonal polyneuropathy beginning 5 months after
      onset of leflunomide treatment. Etiologic investigations were negative. The
      symptoms rapidly improved after withdrawing leflunomide. DISCUSSION: The analysis
      of drug watch data found twelve patients with leflunomide-related neuropathy. Ten
      of them were more than 60 years old. The mean delay for onset of neuropathy was 9
      months. The neuropathy improved after treatment withdrawal in seven patients.
      CONCLUSION: We consider these data strongly suggest that leflunomide is a cause
      of axonal sensory-motor neuropathy. The prevalence of such adverse events is
      still unknown.

PMID- 16288177
TI  - [Investigation of set-shifting ability in patients with Parkinson's disease:
      influence of task sequence type].
AB  - INTRODUCTION: The aim of the present study was to investigate the origin of set
      shifting deficits observed in Parkinson's disease (PD). METHODS: Seventeen
      patients diagnosed as having idiopathic PD were compared with 15 control
      subjects. We used a task-switching paradigm, including two tasks (task A and task
      B) so that subjects were required to switch either immediately after a switch
      trial (i.e. alternating switch or ABA task sequence) or following one or two non
      switch trials (ABBA or ABBBA task sequences). RESULTS: In both groups, switch
      cost (SC) in ABA task sequence was larger than SC in ABBA task sequence (p<0.05)
      and SC was larger in ABBA than ABBBA task sequence (p<0.05). PD patients
      demonstrated an increased SC compared to controls for alternating switch trials
      (p<0.01). Alternatively, when required to switch to a task abandoned two or three
      trials earlier (i.e. ABBA and ABBBA tasks sequences), patients did not
      demonstrate increased SC compared to controls. DISCUSSION AND CONCLUSION: The
      fact that SC associated with alternating switch trials was exacerbated in PD
      patients may reflect difficulties for switching to a recently inhibited task-set.
      In conclusion, our results indicate that set-shifting deficits in PD patients may
      depend of the type of task sequence.

PMID- 16288178
TI  - [Serious tolpcapone-induced hepatitis 17 months after commencing treatment].

PMID- 16288180
TI  - [Transcranial magnetic stimulation: applications in neurology].
AB  - INTRODUCTION: Transcranial magnetic stimulation (TMS) was first applied to assess
      conduction time along the corticospinal tract, namely by recording motor evoked
      potentials. STATE OF ART: At present, TMS techniques include cortical
      excitability and mapping studies using single or paired-pulse paradigms on the
      one hand, and repetitive TMS to induce cortical plasticity and to modify brain
      function on the other hand. TMS is a valuable, non-invasive tool in the diagnosis
      and the pathophysiological assessment of cortical dysfunction involved in various
      neurological diseases (multiple sclerosis, myelopathy, amyotrophic lateral
      sclerosis, movement disorders, epilepsy, stroke). PERSPECTIVES AND CONCLUSION: In
      the near future, repetitive TMS could have therapeutic applications in neurology
      (epilepsy, stroke rehabilitation program) as is already the case in some
      psychiatric diseases. However, most of the new indications for treatment with
      cortical stimulation will be based on surgically-implanted neuromodulation
      procedures.

PMID- 16288181
TI  - [Neuroimaging characteristics of cerebral infarcts].
AB  - Over the last years, technical advances in neuroimaging have allowed drastic
      improvements in the assessment of acute ischemic cerebral events. Beyond
      conventional morphological analysis, diffusion-weighted and perfusion-weighted
      MRI now enable routine functional assessment of brain tissue; spectroscopy and
      diffusion tensor imaging still remains in the domain of clinical research. During
      acute ischemia events, diffusion-weighted MRI can detect the movements of water
      molecules and cytotoxic edema related to cell injury enabling rapid diagnosis and
      early assessment of cerebral ischemia. In conjunction with perfusion imaging,
      which detects hypoperfusion areas, diffusion-weighted MRI provides a means to
      identify areas of penumbra ischemia. More recent multislice computed tomographic
      (CT) scans with multimodal analysis are also very competitive for assessment of
      cerebral ischemia (non-enhanced CT, CT angiography and perfusion CT). The purpose
      of this paper is to describe the CT and MRI patterns during the different stages
      of cerebral infarcts.

PMID- 16288182
TI  - Plasma substitutes.
AB  - Adequate restoration of intravascular volume remains an important therapeutic
      manoeuvre in managing the surgical, medical and the critically ill intensive care
      patient. Definition of the ideal volume replacement strategy still remains one of
      the burning problems. The choice between colloid and crystalloid solutions
      continues to generate controversy. The highly controversial crystalloid/colloid
      dispute has been enlarged to a colloid/colloid debate because aside of the
      natural colloid albumin several non-protein (synthetic) colloids are available as
      plasma substitutes (e.g. dextrans, gelatins, hydroxyethyl starch [HES]
      solutions). Due to their varying physico-chemical properties, these solutions
      widely differ with regard to their pharmacokinetic and pharmacodynamic properties
      as well as to their hemodynamic efficacy and side-effects. HES is the most
      intensively studied plasma substitute. The different HES preparations are defined
      by concentration, molar substitution (MS), mean molecular weight (MW), and the
      C2/C6 ratio of substitution. Two new HES specification, a third-generation HES
      with a lower Mw and a lower MS (6% HES 130/0.4) than all other HES preparation
      and a first-generation HES prepared in a balanced solution, may be promising by
      improving the therapy of the hypovolemic patient. Albumin cannot be recommended
      for correction of hypovolemia because of ist extreme costs and because it can
      easily be replaced by other no-protein colloids. Dextrans should also not be used
      any more due to the negative effects on coagulation and its high anaphylactic
      potency. The historical crystalloid/colloid controversy has been focused
      primarily on outcome. There is increasing evidence that outcome (mortality) is
      not the correct measure when assessing the ideal volume replacement strategy. New
      concepts about critical care such as organ perfusion and organ function, the role
      of inflammation, immunological aspects, and wound healing may change this point
      of view. Volume replacement has been hitherto often based on art, dogma and
      personal beliefs. Further well-performed studies in this area will help more to
      shed new light on the ideal volume replacement strategy of the hypovolemic
      patient than more meta-analyses that are pooling old-to-very old studies to solve
      this problem.

PMID- 16288183
TI  - Glucocorticoids and sepsis.
AB  - Although systemic inflammation is the hallmark of sepsis, the use of
      glucocorticoids remained controversial during many years. Gluco-corticoids exert
      key actions during sepsis, interacting with metabolism, immune and cardiovascular
      systems. Glucocorticoid insufficiency is common during sepsis and may result from
      insufficient production of cortisol or peripheral tissues resistance. Thus,
      recent randomised trials showed that a replacement therapy with long course of
      low dose corticosteroids reduced mortality from septic shock. Improvement in
      survival may result from reduced duration of shock, alleviation of the systemic
      inflammatory response, and reduction in the number and intensity of organs
      dysfunction. This article summarises why, when and how glucocorticoids should be
      used in the management of septic shock.

PMID- 16288184
TI  - Similar preoperative hemodynamic response to pancuronium and rocuronium in high
      risk cardiac surgical patients.
AB  - AIM: Rocuronium may be a good alternative to pancuronium in cardiac surgical
      patients. We evaluate the hemodynamic response to rocuronium and pancuronium
      administered to cardiac surgical patients. METHODS: A single-blind, randomized
      clinical trial was carried out at the National Institute of Cardiology in Mexico.
      Twenty-two patients older than 18 years, NYHA class III-IV, and scheduled to
      undergo an elective cardiovascular surgical procedure were enrolled. Patients
      were randomly allocated to receive an i.v. bolus dose of either pancuronium 100
      microg/kg or rocuronium 600 microg/kg. Peripheral arterial (radial) and venous
      cannulations and insertion of a multi-lumen pulmonary artery flotation catheter
      through the right internal jugular vein were carried out under local anesthesia.
      Anesthetic induction with an i.v. bolus dose of fentanyl 700 microg and diazepam
      20 mg was performed and thereafter the neuromuscular blocking agent was
      administered. Ventilation with O2 100% was performed until a TOF < or =5% was
      observed and tracheal intubation was performed. After intubation, patients were
      maintained with O2 10 mL/kg administered by means of a pulmonary ventilator at a
      pressure of 20-25 cm H2O. The basal, pre-laryngoscopy, post-intubation, and pre
      operative recording of a set of cardiovascular parameters were obtained. RESULTS:
      No differences (P>0.05) in the hemodynamic response were observed between
      pancuronium and rocuronium nor during the different evaluation times in each
      group. CONCLUSIONS: Rocuronium can be a safe alternative to pancuronium for
      patients requiring cardiac surgical procedures.

PMID- 16288185
TI  - High myocardial lactate concentration is associated with poor myocardial function
      prior to cardiopulmonary bypass.
AB  - AIM: This study was designed to analyse the relationship between myocardial
      lactate--determined by microdialysis--and hemodynamics during coronary artery
      bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: Twenty
      consecutive patients with coronary artery disease were enrolled for this
      prospective, observational study. Microdialysis measurements were performed in
      the apical region of the heart during periods of 15 to 20 min before, during, and
      after CPB; hemodynamics and plasma lactate concentrations were determined
      correspondingly. Correlation analysis revealed a relationship between myocardial
      lactate concentration and right ventricular ejection fraction at baseline
      (Spearman's r: 0.6; P=0.02). Patients were thus grouped according to the
      myocardial lactate concentration at baseline into a high-lactate group (2.5+/-0.7
      mmol.l(-1), n=10) and low-lactate group (0.9+/-0.5 mmol.l(-1), n=10). RESULTS:
      Preoperative left ventricular ejection fraction was not different between the
      groups (high-lactate group: 53+/-16%; low-lactate group: 57+/-15%; P=n.s.)
      Patients in the high-lactate-group had a lower stroke volume index (P=0.005) and
      right ventricular ejection fraction (P=0.04) before, and higher central venous
      and pulmonary artery pressures (P<0.01) after CPB. Plasma lactate was
      significantly higher during CPB in the high-lactate-group (P<0.05). No
      correlation was observed between myocardial and plasma lactate. Six patients in
      the high-lactate but none in the low-lactate-group needed inotropic support after
      weaning from CPB (P=0.01). CONCLUSIONS: These data are suggestive of an
      association between subtle myocardial ischemia--detected by microdialysis--and
      perioperative myocardial dysfunction in patients undergoing CABG. The
      microdialysis technique may be a valuable adjunct for monitoring myocardial
      metabolism during cardiac surgery.

PMID- 16288186
TI  - Systemic and organ dysfunction response during infusion of recombinant human
      activated protein C (rhAPC) in severe sepsis and septic shock.
AB  - AIM: The aim of this study was the assessment of the efficacy of recombinant
      human activated protein C (rhAPC) in septic patients. METHODS: A continuous
      observational prospective study on ICU patients with severe sepsis and septic
      shock was carried out. Applying the inclusion criteria of a national trial on the
      use of rhAPC, 15 patients (12 males and 3 females) were enrolled, mean age was
      65.9 (SD 9.6), APACHE II score was > or =25. The following variables were
      assessed on 7 time-points (T1-T7): overall SOFA score; organ-specific SOFA score;
      APACHE II score; PCR, APTT, INR, fibrinogen, platelet count. Wilcoxon's
      statistical test and Spearman's correlation test (rho coefficient) between the
      SOFA and APACHE II scores were used. Test results with a P value below 0.05 were
      deemed significant. RESULTS: A significant correlation was identified between the
      APACHE II and SOFA scores. No significant change was found in Friedman's test and
      the respiratory, haematological and hepatic SOFA score, whereas cardiovascular,
      renal and neurological SOFA scores showed a significant trend between the ranks
      at the 7 time-points (chi2=14; df=6; P=0.029). During rhAPC treatment Friedman's
      test showed significant changes of PCR values over the 7 time-points (chi2=19.2;
      df=6; P=0.02). Wilcoxon's test indicated a significant decrease in the values
      recorded during the T2-T6 period. On day 28, 12 of the 15 patients originally
      enrolled were still alive. Mortality rate was therefore 20% (CI 95%).
      CONCLUSIONS: RhAPC is the first biological agent approved for the treatment of
      severe sepsis and septic shock. Our experience is confined to patients with
      severe sepsis and septic shock, and some severity indexes showed a modulation of
      the inflammatory processes and haemostatic balance, 2 factors which play a key
      role in the evolution of sepsis and organ dysfunction.

PMID- 16288187
TI  - Refeeding syndrome in early pregnancy. Case report.
AB  - Refeeding syndrome is a very serious disorder that is not often observed today,
      as it is more common during times of mass starvation or war. Nowadays, it is
      sometimes found in patients suffering from anorexia nervosa or neoplastic
      diseases. A case recently treated in our Intensive Care Unit is described. The
      patient was pregnant and suffering from Crohn's disease. It is emphasized that
      although refeeding syndrome is often fatal if not treated early, it is easily
      prevented or treated with adequate nutritional support.

PMID- 16288188
TI  - Adult syringomielia. Classification, pathogenesis and therapeutic approaches.
AB  - Syringomyelia is characterized by the presence of cystic cavities inside the
      spinal cord, with an incidence estimated of 8.4 new cases/year/100 000 people.
      The cavities are usually located inside the cervical cord, although they can
      extend upwards and/or downwards. The underlying cause of all types of
      syringomyelia is an alteration in physiologic cerebrospinal fluid (CSF) flow
      dynamics. Four different main types may be described in descending order of
      frequency: associated with Chiari I malformations, associated with vertebral
      trauma, associated with basilar invagination and associated with hydrocephalus.
      Conservative treatment is not recommended as the surgical procedure stops the
      progress of the disease with clinical improvement being the rule. Early surgical
      treatment is highly recommended before the establishment of gross neurological
      deficits occurs. Treatment is urged in case of clinical deterioration or when the
      follow-up MRI studies show increase in size and extension of the syringomyelic
      cavity. The first step in the surgical treatment is a precise diagnosis of its
      etiology to direct the treatment to the underlying cause. Treatment directed to
      normalize CSF flow homeostasis should be case tailored. Surgical measures that
      aim to reconstruct the continuity of the subarachnoid space at the site of the
      block are the first treatment option. Shunting is advocated when reestablishment
      of the pathways proves impossible or as a second procedure.

PMID- 16288189
TI  - Supratentorial low-grade gliomas. Neuroradiology.
AB  - The radiologic modality that most likely provides the imaging information needed
      in a patient suspected of having a brain tumors is magnetic resonance imaging. A
      brain tumors can be reliably ruled out, if the standard magnetic resonance
      examination is performed properly and experts interpret the results as negative
      for tumor. In this paper we will illustrate morphological aspects of low-grade
      supratentorial neoplasms, including tumors of neuroepithelial tissue, such as low
      grade diffuse fibrillary astrocytomas, and circumscribed astrocytic lesions
      (pilocytic astrocytoma, pleomorphic xantoastrocytoma and subependymal giant cell
      astrocytoma). Then the main practical applications of functional imaging in
      neurosurgery will be also debated.

PMID- 16288191
TI  - Characteristics and surgery of aneurysms of the proximal (A1) segment of the
      anterior cerebral artery.
AB  - AIM: Proximal anterior cerebral artery (A1) aneurysms are considered to be rare
      or even unique. Proper surgical planning around A1 segment is particularly
      essential in order to avoid injury of tiny perforating arteries. METHODS: In 17
      patients with angiographically or intraoperatively diagnosed A1 aneurysms,
      representing 0.8% of 2 124 aneurysm patients treated surgically at our
      institution between 1991 and 2003, clinical presentation, neuroradiological
      findings, surgical treatment methods and outcome were retrospectively analyzed.
      RESULTS: Sixteen patients presented with subarachnoid hemorrhage; A1 aneurysms
      were ruptured in 13 cases. Five patients (29%) had multiple aneurysms. In all
      cases A1 aneurysms were saccular and their maximum diameter ranged from 4 to 25
      mm, average, 7.2 mm; in 4 cases they projected from the origin of the perforating
      artery, in 6 at the bifurcation of the internal carotid artery, in 5 at the
      anterior communicating artery and in 2 from the convexity of the parent artery.
      In 15 patients aneurysms were clipped via ipsilateral pterional approach and in
      the remaining 2, including a case with a second middle cerebral artery aneurysm,
      through contralateral approach. Eleven patients had excellent outcome, three
      good, and three died. CONCLUSIONS: Angiograms must be thoroughly analyzed to
      correctly assess origin of the aneurysmal neck, and to plan the operative
      procedure as radiological presentations of distal or proximal A1 lesions resemble
      those of anterior communicating artery and internal carotid artery bifurcation
      aneurysms, respectively. Contralateral approach may facilitate surgical
      elimination of selected A1 aneurysms or enable one-stage clipping in patients
      with multiple bilateral aneurysms.

PMID- 16288190
TI  - Resection of giant meningiomas of the anterior cranial fossa using orbital
      osteotomies.
AB  - AIM: The challenge in large cranial base meningiomas is total resection of the
      tumor with the least possible mortality and morbidity. During the last two
      decades the technical approaches for anterior skull base tumors have shown a
      considerable progress, providing a wide exposure with minimal brain retraction.
      The purpose of this study is to present our experience with these approaches for
      treatment of giant anterior cranial fossa meningiomas. METHODS: A retrospective
      analysis was performed in 20 patients with giant meningiomas (diameter >4.5 cm)
      of the anterior cranial fossa, which were treated surgically in our department,
      between January 1992 and January 2002. There were 5 men and 15 women with an
      average age of 48,3 years. Mental and visual disturbances were the most common
      presenting symptoms. We used the extended subfrontal approach for 16 patients and
      the fronto-orbito-zygomatic approach for 4 patients. The follow-up period ranged
      from 3 to 10 years. RESULTS: In all patients, total resection of the tumor
      (Simpson grade I, 12 patients, Simpson grade II, 8 patients) was accomplished.
      Significant improvement occurred by the time of follow-up examination in all but
      three patients. No evidence of recurrence was observed in 19 of the 20 patients.
      CONCLUSIONS: The extended anterior skull base approaches, using orbital
      osteotomies, for giant meningiomas of the anterior cranial fossa have improved
      the extent of radical tumor removal with minimal neurological morbidity.
      Furthermore a long term prevention of recurrence was achieved.

PMID- 16288192
TI  - Neuroendoscopic management of hydrocephalus secondary to midline and pineal
      lesions.
AB  - AIM: In patients with space-occupying lesions of the pineal region, increased
      intracranial pressure is due to direct compression of the sylvian aqueduct. Based
      on results of the recent literature, neuroendoscopic management of obstructive
      hydrocephalus, secondary to tumors of the pineal gland, has gained a preeminent
      role respect to shunting procedures. METHODS: In 14 select cases, hydrocephalus
      was secondary to midline and pineal lesions. The patient's age ranged from 1 to
      56 years (mean 47.3+/-12.5), with a follow-up ranged from 3 months to 5 years
      after discharge. In 9 cases the endoscopic procedure represented the only
      surgical treatment. In 5 cases, microsurgical removal of the lesions and/or
      ventriculo-peritoneal shunts placement were performed, as additional treatment,
      while adjuvant radiotherapy was utilized in 4 cases; high dose chemotherapy
      followed by bone marrow transplantation was performed in 3 cases. RESULTS: In our
      series, obstructive hydrocephalus secondary to midline and pineal lesions, was
      successful treated by neuroendoscopic approach alone in 9 cases, with an
      unremarkable course and good outcome, except in 1 case. CONCLUSIONS:
      Neuroendoscopic approach affords a minimally invasive way to obtain 4 objectives
      by one-step surgical approach, such as resolution of obstructive hydrocephalus by
      endoscopic third ventriculostomy (ETV), cerebrospinal fluid sample to detect
      tumor markers and to perform cytological analysis, biopsy specimens and tissue
      diagnosis, associated to absence of shunt-related complications. Therefore, in
      experienced hands, ETV should be the treatment of first choice, in cases of
      hydrocephalus secondary to lesions of the pineal gland.

PMID- 16288193
TI  - Vasospasm of venous grafts in extra-intracranial by-pass. Report of two cases.
AB  - Two patients are described, the first with a giant aneurysm of the left carotid
      bifurcation previously treated by endovascular technique, the second with a
      bilateral intracavernous aneurysm: both were submitted to high-flow by-pass
      operation. The first patient was a 40 year-old woman who had presented
      subarachnoid hemorrhage 6 months before operation. She had been treated by means
      of a high-flow by-pass between the external carotid artery and the middle
      cerebral artery. Control angiograms performed 12 hours later showed a stenosis
      above the suture between the external carotid artery and the venous graft.
      Angioplasty was performed by endovascular route: new angiograms showed occlusion
      of the graft while dopplersonography demonstrated the presence of flow within the
      graft. Angiograms performed 1 week later showed marked vasospasm of the venous
      graft, of the internal carotid artery, the anterior cerebral artery and the
      middle cerebral artery. The evolution of spasm of the graft and of the
      intracranial arterial flow was monitored by dopplersonography and MR-angiography:
      the latter was performed 20 days after the last angiography and confirmed patency
      of the graft, while dopplersonography showed resolution of vasospasm. Finally,
      the aneurysm was embolized. The second patient was a 49 year-old woman with mild
      left palpebral ptosis and retro-orbital pain. She had already been submitted to
      high-flow by-pass operation 7 months earlier to treat a right intracavernous
      aneurysm; the left by-pass was necessary because the intracavernous aneurysm had
      become symptomatic. One week after surgery, spasm of the venous graft was
      documented by MR-angiography. In both cases, treatment consisted of calcium
      antagonists as well as hypertensive and hypervolemic medication, which was
      successful in treating vasospasm of the venous graft and its symptoms. Spasm of
      the venous graft, a well-known occurrence in cardiac revascularization, can also
      be observed in cerebral revascularization.

PMID- 16288194
TI  - Serial changes in the regional cerebral blood flow of patients with hypertensive
      intracerebral hemorrhage -- long-term follow-up SPECT study.
AB  - We analyzed serial changes in the regional cerebral blood flow (rCBF) of 13
      patients with intracerebral hemorrhage by single photon emission computed
      tomography (SPECT) during the acute- to chronic stage (2 hr to 55 weeks). The
      (99m)Tc-ethyl cysteinate dimmer ((99m)Tc-ECD) was used as the nuclear mediator.
      The SPECT timing within 48 hours after the onset was considered to be acute
      stage, from 48 hours to 4 weeks to be subacute stage, and after 4 weeks to be
      chronic stage. The region of interest was each hemisphere in the whole brain
      without ventricles at the thalamic level. For semi-quantitative analysis of rCBF,
      we used the Brain Uptake Ratio method. Of the 13 patients (mean age 65.5 years),
      3 had thalamic-, 4 putaminal-, 5 subcortical-, and one a cerebellar hemorrhage;
      the hematoma volume varied from 4-50 ml (<20 ml, n=9; 20-30 ml, n=1; >30 ml, n=3;
      mean 17 ml). The rCBF changes during the long-term follow-up were classified as
      increase-, decrease-, and unchanged type. Of 5 patients with increased rCBF, 4
      made a good recovery and one was severely disabled; of 5 patients with decreased
      rCBF, 1 made a good recovery, 3 were moderately-, and one was severely disabled.
      All 3 patients with unchanged rCBF were moderately disabled. Our findings suggest
      that among patients with hypertensive intracerebral hemorrhage, those with
      increased rCBF over time may have a favorable outcome. We further need more cases
      with intracerebral hemorrhage to clarify this trend.

PMID- 16288195
TI  - Central neurocytoma of the fourth ventricle. Case history.
AB  - Central neurocytomas are low-grade tumours of neuronal origin, affecting mainly
      young patients and usually located in the lateral or third ventricle. We report a
      rare case of central neurocytoma at the fourth ventricle level. Magnetic
      resonance imaging showed a homogeneously enhancing mass lesion at the fourth
      ventricle. Gross-total surgical removal was achieved. The histological diagnosis
      was of central neurocytoma but the lesion showed a fairly elevated Ki-67 index
      (6%). Given this finding, close neuroimaging monitoring was performed and at the
      moment the patient is free of recurrence.

PMID- 16288196
TI  - Protocadherin-21 (PCDH21), a candidate gene for human retinal dystrophies.
AB  - PURPOSE: It has been demonstrated that mice lacking a functional copy of prCAD,
      the gene encoding protocadherin-21, show progressive photoreceptor degeneration.
      Therefore we searched for a human retinal phenotype associated with mutations in
      the orthologous human gene, PCDH21. METHODS: We characterized the genomic
      organization of human PCDH21 and performed mutation screening in 224 patients
      with autosomal recessive retinitis pigmentosa, 29 patients with Leber congenital
      amaurosis, and 26 patients with Usher syndrome type 1. RESULTS: PCDH21 spans 23
      kb, consists of 17 exons, and encodes a protein that shows close phylogenetic
      relationship to cadherin-23 (CDH23), the protein involved in Usher syndrome type
      1D. In a total of three unrelated patients, we identified two different
      heterozygous missense changes (p.A212T and p.P532A), affecting evolutionarily
      conserved residues, that were not found in 100 unaffected controls. A second
      mutation allele was not detected. A novel intragenic microsatellite marker was
      identified. CONCLUSIONS: PCDH21 mutations are not a major cause of the retinal
      diseases investigated herein, and the corresponding human phenotype remains to be
      determined. Our data may facilitate future investigations of patients with
      various (other) forms of inherited retinal dystrophy.

PMID- 16288197
TI  - Genetic homogeneity for inherited congenital microcoria loci in an Asian Indian
      pedigree.
AB  - PURPOSE: Congenital microcoria is a rare autosomal dominant developmental
      disorder of the iris associated with myopia and juvenile open angle glaucoma.
      Linkage to the chromosomal locus 13q31-q32 has previously been reported in a
      large French family. In the current study, a three generation Asian Indian family
      with 15 congenital microcoria (pupils with a diameter <2 mm) affected members was
      studied for linkage to candidate microsatellite markers at the 13q31-q32 locus.
      METHODS: Twenty-four members of the family were clinically examined and genomic
      DNA was extracted. Microsatellite markers at 13q31-q32 were PCR amplified and run
      on an ABI Prism 310 genetic analyzer and genotyped with the GeneScan analysis.
      Two point and multipoint linkage analyses were performed using the MLINK and
      SUPERLINK programs. RESULTS: Peak two point LOD scores of 3.5, 4.7, and 5.3 were
      found co-incident with consecutive markers D13S154, DCT, and D13S1280. Multipoint
      analysis revealed a 4 cM region encompassing D13S1300 to D13S1280 where the LOD
      remains just over 6.0 Thus we confirm localization of the congenital microcoria
      locus to chromosomal locus 13q31-q32. In addition, eight individuals who had both
      microcoria and glaucoma were screened for glaucoma genes: myocilin (MYOC),
      optineurin (OPTN) and CYP1B1. Using direct sequencing a point mutation (144 G>A)
      resulting in a Q48H substitution in exon 1 of the MYOC gene was observed in five
      of the eight glaucoma patients, but not in unaffected family members and 100
      unrelated controls. CONCLUSIONS: We have confirmed the localization of the
      congenital microcoria locus (MCOR) to 13q31-q32 in a large Asian Indian family
      and conclude that current information suggests this is a single locus disorder
      and genetically homogeneous. When combined with the initial linkage paper our
      haplotype and linkage data map the MCOR locus to a 6-7 cM region between D13S265
      and D13S1280. The DCT locus, a member of the tyrosinase family involved in
      pigmentation, maps within this region. Data presented here supports the
      hypothesis that congenital microcoria is a potential risk factor for glaucoma,
      although this observation is complicated by the partial segregation of MYOC Q48H
      (1q24.3-q25.2), a mutation known to be associated with glaucoma in India. Fine
      mapping and candidate gene analysis continues with the hope that characterizing
      the micocoria gene will lead to a better understanding of microcoria and glaucoma
      causation. The relationship between microcoria, glaucoma, and the MYOC Q48H
      mutation in this family is discussed.

PMID- 16288198
TI  - Joint effects of smoking history and APOE genotypes in age-related macular
      degeneration.
AB  - PURPOSE: Age-related macular degeneration (AMD) is a leading cause of severe
      visual impairment in older adults worldwide. Cigarette smoking is one of the most
      consistently identified environmental risk factors for the disease. Several
      studies have implicated the apolipoprotein E (APOE) gene as modulating AMD risk.
      The purpose of this study was to investigate whether APOE genotypes modify the
      smoking-associated risk of AMD. METHODS: Patients with early- and late-stage AMD
      (n=377) and a group of unrelated ethnically matched controls of similar age
      (n=198) were ascertained at two sites in the southeastern United States. Smoking
      history and APOE genotype distribution in cases and controls were compared by
      multivariable logistic regression. RESULTS: All measures of smoking history
      showed a highly significant association with AMD, and odds ratio estimates were
      consistently higher when only patients with exudative AMD were compared to
      controls. Main effects of APOE genotypes in the overall analysis did not reach
      statistical significance. The analysis of exudative AMD patients suggested that
      the risk increase due to smoking was greatest in carriers of the APOE-2 allele,
      with genotype-specific odds ratios increasing from 1.9 for APOE-4 carriers
      (p=0.11) to 2.2 for APOE-3/3 homozygotes (p=0.007) to 4.6 (p=0.001) for APOE-2
      carriers, compared to nonsmoking APOE-3/3 individuals. Measures of statistical
      interaction indicated more than additive, and possibly more than multiplicative,
      joint effects of APOE and smoking history, however, the interaction was not
      statistically significant on either scale. CONCLUSIONS: We hypothesize that a
      history of smoking is a stronger risk factor for exudative AMD in carriers of the
      APOE-2 allele, compared to carriers of APOE-4 and the most common APOE-3/3
      genotype. To further clarify the association of AMD with APOE and smoking
      history, future studies should consider both factors simultaneously.

PMID- 16288199
TI  - The promoter of inducible nitric oxide synthase implicated in glaucoma based on
      genetic analysis and nuclear factor binding.
AB  - PURPOSE: Nitric oxide has many beneficial functions in the human body at the
      right amounts, but it can also be hazardous if it is produced in amounts more
      than needed and has therefore been studied in relation to several neurological
      and non-neurological disorders. In vitro and in vivo studies demonstrate a
      connection between the inducible form of Nitric Oxide Synthase, iNOS, and the
      neuropathological disorder glaucoma, one of the major causes of blindness in the
      world. In this study, we sought to establish the genetic association between iNOS
      and primary open angle glaucoma, POAG, and to find the functional element(s)
      connected with the pathogenesis of the disease. METHODS: Two microsatellites, 1
      insertion/deletion, and 8 single nucleotide polymorphisms (SNPs) in the
      regulatory region of iNOS were genotyped in 200 POAG patients and 200 age-matched
      controls. Also, the CCTTT-microsatellite was examined for its protein-binding
      capability in an electrophoretic mobility shift assay, EMSA. RESULTS: There was a
      significant difference in allele distribution of the CCTTT-microsatellite,
      between patients and controls. (CCTTT)14, which has been reported to have a
      higher activity in a reporter-construct, was significantly more abundant in POAG
      patients, while (CCTTT)10 and (CCTTT)13 were less common. In EMSA, the (CCTTT)14
      allele exhibited specific binding of nuclear proteins. CONCLUSIONS: These
      results, together with other studies on this gene and the CCTTT-microsatellite,
      establish, for the first time, a genetic association of iNOS with POAG and
      suggest a regulatory function for the microsatellite.

PMID- 16288201
TI  - A new congenital nuclear cataract caused by a missense mutation in the gammaD
      crystallin gene (CRYGD) in a Chinese family.
AB  - PURPOSE: To identify genetic defects associated with nuclear golden crystal
      autosomal dominant congenital cataract (ADCC) in a Chinese pedigree in the north
      of China. METHODS: Clinical data were collected and the phenotype of the affected
      members in this family was recorded by slit lamp photography. Genomic DNA was
      isolated from peripheral blood. Linkage analyses excluded all known loci except
      that in 2q33-q35. Mutation analysis of CRYGs was carried by direct sequencing of
      the PCR products. RESULTS: Sequencing of the coding regions of CRYGA, CRYGB,
      CRYGC, and CRYGD showed the presence of a heterozygous C>A transversion at nt109
      of the coding sequence (R36S) in exon 2 of CRYGD, which co-segregated with the
      affected members. CONCLUSIONS: The R36S mutation in CRYGD identified in this
      Chinese family caused a nuclear golden crystal cataract phenotype not described
      before. This finding is an additional indication that there may be phenotypic
      heterogeneity of cataract, especially in different races.

PMID- 16288202
TI  - Nf1 haploinsufficiency augments angiogenesis.
AB  - Mutations in the NF1 tumor-suppressor gene underlie neurofibromatosis type 1
      (NF1), in which patients are predisposed to certain tumors such as neurofibromas
      and may associate with vascular disorder. Plexiform neurofibromas are slow
      growing benign tumors that are highly vascular and can progress to malignancy.
      The development of neurofibromas requires loss of both Nf1 alleles in Schwann
      cells destined to become neoplastic and may be exacerbated by Nf1 heterozygosity
      in other non-neoplastic cells. This study tested the hypothesis that Nf1
      heterozygosity exaggerates angiogenesis. We found that Nf1 heterozygous mice
      showed increased neovascularization in both the retina and cornea in response to
      hypoxia and bFGF, respectively, compared to their wild-type littermates. The
      increase in corneal neovascularization was associated with heightened endothelial
      cell proliferation and migration, and increased infiltration of inflammatory
      cells. In addition, Nf1 heterozygous endothelial cell cultures showed an
      exaggerated proliferative response to angiogenic factors, particularly to bFGF.
      These findings support the conclusion that Nf1 heterozygosity in endothelial
      cells and perhaps inflammatory cells augments angiogenesis, which may promote
      neurofibroma formation in NF1.

PMID- 16288200
TI  - Genetic networks controlling retinal injury.
AB  - PURPOSE: The present study defines genomic loci underlying coordinate changes in
      gene expression following retinal injury. METHODS: A group of acute phase genes
      expressed in diverse nervous system tissues was defined by combining microarray
      results from injury studies from rat retina, brain, and spinal cord. Genomic loci
      regulating the brain expression of acute phase genes were identified using a
      panel of BXD recombinant inbred (RI) mouse strains. Candidate upstream regulators
      within a locus were defined using single nucleotide polymorphism databases and
      promoter motif databases. RESULTS: The acute phase response of rat retina, brain,
      and spinal cord was dominated by transcription factors. Three genomic loci
      control transcript expression of acute phase genes in brains of BXD RI mouse
      strains. One locus was identified on chromosome 12 and was highly correlated with
      the expression of classic acute phase genes. Within the locus we identified the
      inhibitor of DNA binding 2 (Id2) as a candidate upstream regulator. Id2 was
      upregulated as an acute phase transcript in injury models of rat retina, brain,
      and spinal cord. CONCLUSIONS: We defined a group of transcriptional changes
      associated with the retinal acute injury response. Using genetic linkage analysis
      of natural transcript variation, we identified regulatory loci and candidate
      regulators that control transcript levels of acute phase genes.

PMID- 16288203
TI  - The N-terminus of rodent and human MAD1 confers species-specific stringency to
      spindle assembly checkpoint.
AB  - The spindle assembly checkpoint (SAC) guards against chromosomal mis-segregation
      and the emergence of aneuploidy. SAC in higher eukaryotes includes at least 10
      proteins including MAD1-3, BUB1-3, and Msp1. A long-standing observation has been
      that rodent cells are more tolerant of microtubule toxins than primate cells
      indicating that SAC function is more relaxed in the former than the latter. Here,
      we report on an unexpected functional difference between the rodent and human
      MAD1 component of the respective SAC. Ectopic expression of human MAD1 in mouse
      and hamster cells corrected a relaxed SAC to a more stringent form. Our findings
      posit MAD1 as a species-specific determinant which influences the stringency of
      cellular response to microtubule depolymerization and spindle damage.

PMID- 16288204
TI  - Apoptin-induced cell death is modulated by Bcl-2 family members and is Apaf-1
      dependent.
AB  - Apoptin, a chicken anemia virus-derived protein, selectively induces apoptosis in
      transformed but not in normal cells, thus making it a promising candidate as a
      novel anticancer therapeutic. The mechanism of apoptin-induced apoptosis is
      largely unknown. Here, we report that contrary to previous assumptions, Bcl-2 and
      Bcl-xL inhibit apoptin-induced cell death in several tumor cell lines. In
      contrast, deficiency of Bax conferred resistance, whereas Bax expression
      sensitized cells to apoptin-induced death. Cell death induction by apoptin was
      associated with cytochrome c release from mitochondria as well as with caspase-3
      and -7 activation. Benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, a broad
      spectrum caspase inhibitor, was highly protective against apoptin-induced cell
      death. Apoptosis induced by apoptin required Apaf-1, as immortalized Apaf-1
      deficient fibroblasts as well as tumor cells devoid of Apaf-1 were strongly
      protected. Thus, our data indicate that apoptin-induced apoptosis is not only Bcl
      2- and caspase dependent, but also engages an Apaf-1 apoptosome-mediated
      mitochondrial death pathway.

PMID- 16288205
TI  - Gene expression profiling of breast cell lines identifies potential new basal
      markers.
AB  - A better molecular characterization of breast cell lines (BCL) may help discover
      new markers to apply to tumour samples. We performed gene and protein expression
      profiling of 31 BCL using whole-genome DNA microarrays and immunohistochemistry
      (IHC) on 'cell microarrays' (CMA), respectively. Global hierarchical clustering
      discriminated two groups of BCL: group I corresponded to luminal cell lines,
      group II to basal and mesenchymal cell lines. Correlations with centroids
      calculated from a published 'intrinsic 500-gene set' assigned 15 cell lines as
      luminal, eight as basal and four as mesenchymal. A set of 1.233 genes was
      differentially expressed between basal and luminal samples. Mesenchymal and basal
      subtypes were rather similar and discriminated by only 227 genes. The expression
      of 10 proteins (CAV1, CD44, EGFR, MET, ETS1, GATA3, luminal cytokeratin CK19,
      basal cytokeratin CK5/6, CD10, and ERM protein moesin) encoded by luminal vs
      basal discriminator genes confirmed the subtype classification and the validity
      of the identified markers. Our BCL basal/luminal signature correctly re
      classified the published series of tumour samples that originally served to
      identify the molecular subtypes, suggesting that the identified markers should be
      useful for tumour classification and might represent promising targets for
      disease management.

PMID- 16288206
TI  - A novel Bcl-x splice product, Bcl-xAK, triggers apoptosis in human melanoma cells
      without BH3 domain.
AB  - Pro- and antiapoptotic proteins of the large Bcl-2 family are critical regulators
      of apoptosis via the mitochondrial pathway. Whereas antiapoptotic proteins of the
      family share all four Bcl-2 homology domains (BH1-BH4), proapoptotic members may
      lack some of these domains, but all so far described proapoptotic Bcl-2 proteins
      enclose BH3. The bcl-x gene gives rise to several alternative splice products
      resulting in proteins with distinct functions as the antiapoptotic Bcl-xL and
      proapoptotic Bcl-xS. Here, we describe a novel Bcl-x splice product of 138 amino
      acids termed Bcl-xAK (Atypical Killer), which encloses the Bcl-2 homology domains
      BH2 and BH4 as well as the transmembrane domain, but lacks BH1 and BH3. Weak
      endogenous expression of Bcl-xAK was seen in melanoma and other tumor cells.
      Interestingly, its overexpression by applying a tetracycline-inducible expression
      system resulted in significant induction of apoptosis in melanoma cells, which
      occurred in synergism with drug-induced apoptosis. After exogenous
      overexpression, Bcl-xAK was localized both in mitochondrial and in cytosolic cell
      fractions. By these findings, a completely new class of Bcl-2-related proteins is
      introduced, which promotes apoptosis independently from the BH3 domain and
      implies additional, new mechanisms for apoptosis regulation in melanoma cells.

PMID- 16288207
TI  - Regulation of p53 and suppression of apoptosis by the soluble guanylyl
      cyclase/cGMP pathway in human ovarian cancer cells.
AB  - Dysregulated apoptosis plays a critical role in the development of a number of
      aberrant cellular processes, including tumorigenesis and chemoresistance.
      However, the mechanisms that govern the normal apoptotic program are not
      completely understood. Soluble guanylyl cyclase (sGC) and cyclic guanosine
      monophosphate (cGMP) promote mammalian cell viability via an unknown mechanism
      and p53 status is a key determinant of cell fate in human ovarian cancer cells.
      Whether an interaction exists between these two determinants of cell fate is
      unknown. We hypothesized that basal sGC activity reduces p53 content and
      attenuates p53-dependent apoptosis in human ovarian cancer cells. Suppression of
      sGC activity with the specific inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1
      one (ODQ) lowered cGMP content, and increased p53 protein content and induced
      apoptosis in three ovarian cancer cell lines, effects which were attenuated by
      the cGMP analog 8-Br-cGMP and by Atrial Natriuretic Factor, an activator of
      particulate guanylyl cyclase, which circumvent the inhibition of sGC. ODQ
      prolonged p53 half-life, induced phosphorylation of p53 on Ser15, and upregulated
      the p53-dependent gene products p21, murine double minute-2, and the
      proapoptotic, p53-responsive gene product Bax. ODQ activated caspase-3, and ODQ
      induced apoptosis was inhibited by overexpression of X-linked inhibitor of
      apoptosis Protein. Pretreatment with the specific p53 inhibitor pifithrin or
      downregulation of p53 using a specific small inhibitory RNA significantly
      attenuated ODQ-induced apoptosis. Moreover, ODQ-induced upregulation of p21 and
      Bax and ODQ-induced apoptosis were significantly reduced in a p53 mutant cell
      line relative to the wild-type parental cell line. Thus, the current study
      establishes that basal sGC/cGMP activity regulates p53 protein stability,
      content, and function, possibly by altering p53 phosphorylation and
      stabilization, and promotes cell survival in part through regulation of caspase-3
      and p53.

PMID- 16288208
TI  - AP2alpha alters the transcriptional activity and stability of p53.
AB  - AP2alpha and p53 form nuclear complexes that establish a functional partnership,
      which regulates the expression of certain genes involved in cell growth and
      metastasis. The growth effects of AP2alpha are mediated through p21WAF1/CIP1 and
      the ability for AP2alpha to coactivate p21 requires p53. Herein, we have
      localized the AP2-binding region of p53 to amino acids 305-375. Analysis of 26
      distinct p53 alleles established a correlation between AP2alpha binding and
      transcriptional coactivation. The L350P point mutation was the only nonbinding
      allele that retained normal transcriptional activity by reporter assay. Although
      both wild-type and L350P alleles facilitated binding of AP2alpha to the p21
      promoter, the L350P allele was significantly reduced in its ability to induce the
      endogenous p21 gene, demonstrating a striking difference in activity comparing
      reporter assays with activation of endogenous p53 target genes. Interestingly,
      expression of AP2 in the absence of radiation repressed p53-mediated induction of
      p21 and this effect was explained by a reduction in p53 stability induced by
      AP2alpha overexpression. We conclude that AP2alpha has competing effects on p53
      activity through coactivation and decreased stability. These findings may provide
      a mechanism to account for the discrepancies reported for the association between
      AP2 and p21 expression in tumor tissue.

PMID- 16288209
TI  - An osteopontin splice variant induces anchorage independence in human breast
      cancer cells.
AB  - In malignant tumors, metastasis genes are typically deregulated by aberrant
      expression or splicing. Osteopontin is expressed at high levels by various
      cancers and contributes importantly to their invasive potential. In contrast,
      osteopontin derived from host cells induces cellular immunity and could bolster
      antitumor protection by cytotoxic T lymphocytes. Here we show that breast cancer
      cells express multiple splice variants of osteopontin. According to RT-PCR
      analysis of human breast tissue specimens, the splice variant osteopontin-c is a
      highly specific marker for transformed cells, which is not expressed in their
      surrounding normal tissue. The full-length form of osteopontin aggregates in the
      presence of physiologic amounts of calcium and, in this state, leads to enhanced
      cell adhesion. Ostensibly, this effect is inhibitory for tumor cell
      dissemination. The shortest splice variant, osteopontin-c, does not aggregate in
      the presence of calcium and enhances clone formation in soft agar. According to
      microarray analysis, osteopontin-c induces the expression of oxidoreductases,
      consistent with protection from anoikis during anchorage-independent growth.
      These studies define a third functional domain of osteopontin, beside the C
      terminal CD44-binding site and the central integrin-binding site. They also
      provide evidence for a bifunctional character of osteopontin, with the soluble
      form supporting invasiveness and the aggregated form promoting adhesion.

PMID- 16288210
TI  - The E5 protein of BPV-4 interacts with the heavy chain of MHC class I and
      irreversibly retains the MHC complex in the Golgi apparatus.
AB  - BPV-4 E5 inhibits transcription of the bovine MHC class I heavy chain (HC) gene,
      increases degradation of HC and downregulates surface expression of MHC class I
      by retaining the complex in the Golgi apparatus (GA). Here we report that
      transcription inhibition can be alleviated by interferon treatment and the
      degradation of HC can be reversed by treatment with inhibitors of proteasomes and
      lysosomes. However, the inhibition of transport of MHC class I to the cell
      surface is irreversible. We show that E5 is capable of physically interacting
      with HC. Together with the inhibition of the vacuolar ATPase (due to the
      interaction between E5 and 16k subunit c), the interaction between E5 and HC is
      likely to be responsible for retention of MHC class I in the GA. C-terminus
      deletion mutants of E5 are incapable of either downregulating surface MHC class I
      or interacting with HC, establishing that the C-terminus domain of E5 is
      important in the inhibition of MHC class I.

PMID- 16288212
TI  - The phosphoinositide 3-kinase/Akt pathway is essential for the retinoic acid
      induced differentiation of F9 cells.
AB  - Retinoic acid (RA) induces cell growth arrest and differentiation through two
      families of nuclear receptors, the RARs and the RXRs. The phosphoinositide 3
      kinase (PI3K)/Akt pathway also plays key roles in these processes, that is, cell
      cycle progression, cell differentiation and cell survival. We report that, in
      mouse embryocarcinoma cells (F9 cells), RA induces an early activation of PI3K
      and Akt via an increase in the expression of the p85alpha regulatory subunit.
      This effect is followed by an inhibition of Akt. Both effects require the
      integrity of the RA pathway as they are not observed in RA-resistant RARgamma
      null cells. We propose a model through which RA induces a biphasic regulation of
      Akt with an activation participating to the differentiation process, followed by
      an inhibition, which has been correlated to the RA-induced growth arrest.

PMID- 16288211
TI  - Redundancy of DNA helicases in p53-mediated apoptosis.
AB  - A subset of DNA helicases, the RecQ family, has been found to be associated with
      the p53-mediated apoptotic pathway and is involved in maintaining genomic
      integrity. This family contains the BLM and WRN helicases, in which germline
      mutations are responsible for Bloom and Werner syndromes, respectively. TFIIH DNA
      helicases, XPB and XPD, are also components in this apoptotic pathway. We
      hypothesized that there may be some redundancy between helicases in their ability
      to complement the attenuated p53-mediated apoptotic levels seen in cells from
      individuals with diseases associated with these defective helicase genes. The
      attenuated apoptotic phenotype in Bloom syndrome cells was rescued not only by
      ectopic expression of BLM, but also by WRN or XPB, both 3' --> 5' helicases, but
      not expression of the 5' --> 3' helicase XPD. Overexpression of Sgs1, a WRN/BLM
      yeast homolog, corrected the reduction in BS cells only, which is consistent with
      Sgs1 being evolutionarily most homologous to BLM. A restoration of apoptotic
      levels in cells from WS, XPB or XPD patients was attained only by overexpression
      of the specific helicase. Our data suggest a limited redundancy in the pathways
      of these RecQ helicases in p53-induced apoptosis.

PMID- 16288213
TI  - K-ras activation generates an inflammatory response in lung tumors.
AB  - Activating mutations in K-ras are one of the most common genetic alterations in
      human lung cancer. To dissect the role of K-ras activation in bronchial
      epithelial cells during lung tumorigenesis, we created a model of lung
      adenocarcinoma by generating a conditional mutant mouse with both Clara cell
      secretory protein (CC10)-Cre recombinase and the Lox-Stop-Lox K-ras(G12D)
      alleles. The activation of K-ras mutant allele in CC10 positive cells resulted in
      a progressive phenotype characterized by cellular atypia, adenoma and ultimately
      adenocarcinoma. Surprisingly, K-ras activation in the bronchiolar epithelium is
      associated with a robust inflammatory response characterized by an abundant
      infiltration of alveolar macrophages and neutrophils. These mice displayed early
      mortality in the setting of this pulmonary inflammatory response with a median
      survival of 8 weeks. Bronchoalveolar lavage fluid from these mutant mice
      contained the MIP-2, KC, MCP-1 and LIX chemokines that increased significantly
      with age. Cell lines derived from these tumors directly produced MIP-2, LIX and
      KC. This model demonstrates that K-ras activation in the lung induces the
      elaboration of inflammatory chemokines and provides an excellent means to further
      study the complex interactions between inflammatory cells, chemokines and tumor
      progression.

PMID- 16288214
TI  - Dual role of LOH at MMR loci in hereditary non-polyposis colorectal cancer?
AB  - hMLH1 and hMSH2 can be considered tumor suppressor genes, as both alleles must be
      inactivated in order to lose the mismatch repair (MMR) function. In this regard,
      it has been proposed that LOH at MMR loci is a common Knudson's second-hit
      mechanism in HNPCC patients. However, experimental evidence supporting this view
      is scarcely found in the literature. We have performed a comprehensive analysis
      of LOH in 45 HNPCC tumors carrying a germline alteration in MMR loci. Overall, we
      have detected LOH at MMR loci in 56% of the cases. However, up to 40% of the LOH
      events targeted the mutant allele, arguing against a second-hit role in these
      tumors. Interestingly, the age at diagnosis was significantly older in these
      patients. To explain this and previous data, we propose a dual role for LOH at
      MMR loci in HNPCC.

PMID- 16288215
TI  - Id proteins: novel targets of activin action, which regulate epidermal
      homeostasis.
AB  - Activin is a member of the transforming growth factor beta (TGF-beta) family,
      which plays a crucial role in skin morphogenesis and wound healing. To gain
      insight into the underlying mechanisms of action, we searched for activin
      regulated genes in cultured keratinocytes. One of the identified target genes
      encodes Id1, a negative regulator of helix-loop-helix transcription factors. We
      show that Id1, Id2, and Id3 are strongly downregulated by activin in
      keratinocytes in vitro and in vivo. To determine the role of Id1 in keratinocyte
      biology, we generated stable HaCaT keratinocyte cell lines overexpressing this
      protein. Our results revealed that enhanced levels of Id1 do not affect
      proliferation of keratinocytes in monoculture under exponential culture
      conditions or in response to activin or TGF-beta1. However, in three-dimensional
      organotypic cultures, Id1-overexpressing HaCaT cells formed a hyperthickened and
      disorganized epithelium that was characterized by enhanced keratinocyte
      proliferation, abnormal differentiation, and an increased rate of apoptosis.
      These results identify an important function of Id1 in the regulation of
      epidermal homeostasis.

PMID- 16288216
TI  - Microsatellite instability and mutation analysis of candidate genes in urothelial
      cell carcinomas of upper urinary tract.
AB  - A subset of upper urinary tract urothelial cell carcinomas (UUC), arising
      sporadically or as a manifestation of hereditary non-polyposis colorectal cancer,
      displays microsatellite instability (MSI). MSI tumours are characterized by
      defective mismatch repair and accumulation of frameshift mutations in numerous
      genes harbouring repeats in their coding sequences. We have evaluated the
      incidence of MSI in UUC and the intratumoral distribution of mutations in 13
      candidate target genes. A total of 58 unselected UUC were screened for MSI using
      the panel of five mononucleotide markers recently recommended by the National
      Cancer Institute for a precise MSI assessment. Four tumours displayed MSI (7%),
      among which at least three had alterations in the genes MSH3, BAX, MRE11, RAD50.
      Mutations in genes involved in key cellular pathways (ATR, DNA-PKcs, MBD4, TCF-4,
      MSH6, and BLM) were further detected. BAX and MRE11 mutations tend to present
      homogeneously within the three MSI UUC. Immunohistochemistry (MLH1, MSH2, MSH6)
      showed that loss of mismatch repair protein expression occurred in all MSI UUC
      defining the gene defect and that MRE11 and RAD50 mutations were associated with
      their concomitant loss expression. In conclusion, MSI UUC represent a small
      proportion of UUC in which BAX and MRE11 mutations are frequent and may play a
      role early in UUC tumorigenesis.

PMID- 16288217
TI  - Smad4 haploinsufficiency in mouse models for intestinal cancer.
AB  - The Smad4(+/E6sad) mouse carries a null mutation in the endogenous Smad4 gene
      resulting in serrated adenomas and mixed polyposis of the upper gastrointestinal
      (GI) tract with 100% penetrance. Here, we show by loss of heterozygosity (LOH)
      analysis and immunohistochemistry (IHC) that, although the majority of the tumors
      appear at 9 months of age, somatic loss of the wild-type Smad4 allele occurs only
      at later stages of tumor progression. Hence, haploinsufficiency underlies Smad4
      driven tumor initiation in the GI tract. As both the Apc and Smad4 tumor
      suppressor genes map to mouse chromosome 18, we have bred Smad4(+/E6sad) with the
      Apc(+/1638N) model to generate two distinct compound heterozygous lines carrying
      both mutations either in cis (CAS) or in trans (TAS). Strikingly, both models
      show increased tumor multiplicities when compared with the single mutant
      littermates, although CAS mice are more severely affected and became moribund at
      only 5-6 weeks of age. Phenotypic and molecular analyses indicate that Smad4
      haploinsufficiency is sufficient to significantly affect tumor initiation and
      progression both prior to and upon loss of Apc function. Moreover, complete loss
      of Smad4 strongly enhances Apc-driven tumor formation.

PMID- 16288218
TI  - Increased expression of proapoptotic BMCC1, a novel gene with the BNIP2 and
      Cdc42GAP homology (BCH) domain, is associated with favorable prognosis in human
      neuroblastomas.
AB  - Differential screening of the genes obtained from cDNA libraries of primary
      neuroblastomas (NBLs) between the favorable and unfavorable subsets has
      identified a novel gene BCH motif-containing molecule at the carboxyl terminal
      region 1 (BMCC1). Its 350 kDa protein product possessed a Bcl2-/adenovirus E1B
      nineteen kDa-interacting protein 2 (BNIP2) and Cdc42GAP homology domain in the
      COOH-terminus in addition to P-loop and a coiled-coil region near the NH2
      terminus. High levels of BMCC1 expression were detected in the human nervous
      system as well as spinal cord, brain and dorsal root ganglion in mouse embryo.
      The immunohistochemical study revealed that BMCC1 was positively stained in the
      cytoplasm of favorable NBL cells but not in unfavorable ones with MYCN
      amplification. The quantitative real-time reverse transcription-PCR using 98
      primary NBLs showed that high expression of BMCC1 was a significant indicator of
      favorable NBL. In primary culture of newborn mice superior cervical ganglion
      (SCG) neurons, mBMCC1 expression was downregulated after nerve growth factor
      (NGF)-induced differentiation, and upregulated during the NGF-depletion-induced
      apoptosis. Furthermore, the proapoptotic function of BMCC1 was also suggested by
      increased expression in CHP134 NBL cells undergoing apoptosis after treatment
      with retinoic acid, and by an enhanced apoptosis after depletion of NGF in the
      SCG neurons obtained from newborn mice transgenic with BMCC1 in primary culture.
      Thus, BMCC1 is a new member of prognostic factors for NBL and may play an
      important role in regulating differentiation, survival and aggressiveness of the
      tumor cells.

PMID- 16288219
TI  - DLK1: increased expression in gliomas and associated with oncogenic activities.
AB  - DLK1 (delta-like) is a transmembrane and secreted protein in the epidermal growth
      factor-like homeotic family. Although expressed widely during embryonic
      development, only a few tissues retain the expression in adults. Neuroendocrine
      tumors often highly express this protein; therefore, we hypothesized that brain
      tumors might also express it. This study found that the expression of DLK1 in
      gliomas was higher than that in normal brain (P < 0.05). After stable
      transfection of a DLK1 cDNA expression vector into GBM cell lines, their
      proliferation was increased. Furthermore, they lost contact inhibition, had
      enhanced anchorage-independent growth in soft agar, and had significantly greater
      capacity to migrate. Western blot studies showed that expression of cyclin D1,
      CDK2, and E2F4 were increased, and Rb levels were decreased in these cells. DLK1
      was found on the cell surface and secreted in the medium from the transfected GBM
      cells. DLK1-enriched condition medium stimulated the growth of glioblastoma
      multiforme cell lines and explants. DLK1 antibody blocked cell growth stimulated
      by DLK1. In summary, these results suggest that DLK1 may play a role in the
      formation or progression of gliomas.

PMID- 16288221
TI  - Identification of novel E2F1 target genes regulated in cell cycle-dependent and
      independent manners.
AB  - The transcription factor E2F mediates cell cycle-dependent expression of genes
      important for cell proliferation in response to growth stimulation. To further
      understand the role of E2F, we utilized a sensitive subtraction method to explore
      new E2F1 targets, which are expressed at low levels and might have been
      unrecognized in previous studies. We identified 33 new E2F1-inducible genes,
      including checkpoint genes Claspin and Rad51ap1, and four genes with unknown
      function required for cell cycle progression. Moreover, we found three groups of
      E2F1-inducible genes that were not induced by growth stimulation. At least, two
      groups of genes were directly induced by E2F1, indicating that E2F1 can regulate
      expression of genes not induced during the cell cycle. One included Neogenin,
      WASF1 and SGEF genes, which may have a role in differentiation or development.
      The other was the cyclin-dependent kinase inhibitor p27(Kip1), which was involved
      in suppression of inappropriate cell cycle progression induced by deregulated
      E2F. E2F1-responsive regions of these genes were located more upstream than those
      of typical E2F targets and did not have typical E2F sites. These results indicate
      that there are groups of E2F1 targets, which are regulated in a distinct manner
      from that of typical E2F targets.

PMID- 16288222
TI  - Methylational urinalysis: a prospective study of bladder cancer patients and age
      stratified benign controls.
AB  - Tumour suppressor gene (TSG) methylation has been proposed as a diagnostic marker
      for urothelial cancer (UC). Here, we compare the frequency of urinary TSG
      methylation in young and elderly patients, with and without UC. Urine samples
      were obtained prospectively from 35 UC patients, 35 benign controls over the age
      of 70 years and 34 healthy volunteers under the age of 40 years. Methylation
      analysis was performed for eight gene promoters using quantitative methylation
      specific PCR. Methylation was detected in urine DNA from all three patient
      groups. The highest frequencies were seen in UC patients. Significantly less
      methylation was present in control samples than UC cases for RASSF1a and APC (P <
      0.034). The 'methylation index' and level of methylation was highest in the UC
      group and lowest in the young control group. A marker panel of RASSF1a, E-cad and
      APC generated a sensitivity of 69%, a specificity of 60% and a diagnostic
      accuracy of 86%. TSG methylation is detectable in urine DNA from patients with
      and without bladder cancer. The frequency and extent of methylation appears to
      increase with age and malignancy. The lack of tumour specificity suggests that
      further investigation is required before this test is introduced into clinical
      practice.

PMID- 16288220
TI  - Critical interactions between TGF-beta signaling/ELF, and E-cadherin/beta-catenin
      mediated tumor suppression.
AB  - Inactivation of the transforming growth factor-beta (TGF-beta) pathway occurs
      often in malignancies of the gastrointestinal (GI) system. However, only a
      fraction of sporadic GI tumors exhibit inactivating mutations in early stages of
      cancer formation, suggesting that other mechanisms play a critical role in the
      inactivation of this pathway. Here, we show a wide range of GI tumors, including
      those of the stomach, liver and colon in elf+/- and elf+/- / Smad4+/- mutant
      mice. We found that embryonic liver fodrin (ELF), a beta-Spectrin originally
      identified in endodermal stem/progenitor cells committed to foregut lineage,
      possesses potent antioncogenic activity and is frequently inactivated in GI
      cancers. Specifically, E-cadherin accumulation at cell-cell contacts and E
      cadherin-beta-catenin-dependent epithelial cell-cell adhesion is disrupted in
      elf+/- / Smad4+/- mutant gastric epithelial cells, and could be rescued by
      ectopic expression of full-length elf, but not Smad3 or Smad4. Subcellular
      fractionation revealed that E-cadherin is expressed mainly at the cell membrane
      after TGF-beta stimulation. In contrast, elf+/- / Smad4+/- mutant tissues showed
      abnormal distribution of E-cadherin that could be rescued by overexpression of
      ELF but not Smad3 or Smad4. Our results identify a group of common lethal
      malignancies in which inactivation of TGF-beta signaling, which is essential for
      tumor suppression, is disrupted by inactivation of the ELF adaptor protein.

PMID- 16288223
TI  - The PI3K inhibitor LY294002 blocks drug export from resistant colon carcinoma
      cells overexpressing MRP1.
AB  - Multidrug resistance may be achieved by the activation of membrane transporters,
      detoxification, alterations in DNA repair or failure in apoptotic pathways.
      Recent data have suggested an involvement of mitogenic signalling pathways
      mediated by Ras and phosphoinositol-3-kinase (PI3K/Akt) in controlling multidrug
      resistance. Since these pathways are important targets for therapeutic
      interference, we sought to investigate whether blocking effectors kinases by
      specific inhibitors would result in a sensitization toward cytotoxic drugs. We
      found that cotreatment of drug-resistant HT29RDB colon cancer cells with the
      topoisomerase inhibitor doxorubicin and the PI3K-inhibitor LY294002 resulted in
      massive apoptosis, while cotreatment with the Mek inhibitors PD98059 or U0126 had
      no effect. This suggested that the PI3K-pathways controls cell survival and drug
      resistance in these cells. Besides blocking Akt phosphorylation, the PI3K
      inibitor increased the intracellular doxorubicin concentration threefold.
      LY294002 inhibits drug export in a competitive manner as revealed by measuring
      drug efflux in the presence and the absence of inhibitor. The efficacy of drug
      efflux inhibition by LY294002 was similar to that achieved by the MRP1 inhibitors
      MK571 and genistein. We conclude that the PI3K inhibitor LY294002 may have
      therapeutic potential when combined with doxorubicin in the treatment of MRP1
      mediated drug resistance.

PMID- 16288224
TI  - HEF1 is a necessary and specific downstream effector of FAK that promotes the
      migration of glioblastoma cells.
AB  - The highly invasive behavior of glioblastoma cells contributes to the morbidity
      and mortality associated with these tumors. The integrin-mediated adhesion and
      migration of glioblastoma cells on brain matrix proteins is enhanced by
      stimulation with growth factors, including platelet-derived growth factor (PDGF).
      As focal adhesion kinase (FAK), a nonreceptor cytoplasmic tyrosine kinase, has
      been shown to promote cell migration in various other cell types, we analysed its
      role in glioblastoma cell migration. Forced overexpression of FAK in serum
      starved glioblastoma cells plated on recombinant (rec)-osteopontin resulted in a
      twofold enhancement of basal migration and a ninefold enhancement of PDGF-BB
      stimulated migration. Both expression of mutant FAK(397F) and the downregulation
      of FAK with small interfering (si) RNA inhibited basal and PDGF-stimulated
      migration. FAK overexpression and PDGF stimulation was found to increase the
      phosphorylation of the Crk-associated substrate (CAS) family member human
      enhancer of filamentation 1 (HEF1), but not p130CAS or Src-interacting protein
      (Sin)/Efs, although the levels of expression of these proteins was similar.
      Moreover downregulation of HEF1 with siRNA, but not p130CAS, inhibited basal and
      PDGF-stimulated migration. The phosphorylated HEF1 colocalized with vinculin and
      was associated almost exclusively with 0.1% Triton X-100 insoluble material,
      consistent with its signaling at focal adhesions. FAK overexpression promoted
      invasion through normal brain homogenate and siHEF1 inhibited this invasion.
      Results presented here suggest that HEF1 acts as a necessary and specific
      downstream effector of FAK in the invasive behavior of glioblastoma cells and may
      be an effective target for treatment of these tumors.

PMID- 16288225
TI  - Gene expression profiling identifies molecular subgroups among nodal peripheral T
      cell lymphomas.
AB  - The classification of peripheral T-cell lymphomas (PTCL) is still a matter of
      debate. To establish a molecular classification of PTCL, we analysed 59 primary
      nodal T-cell lymphomas using cDNA microarrays, including 56 PTCL and three T
      lymphoblastic lymphoma (T-LBL). The expression profiles could discriminate
      angioimmunoblastic lymphoma, anaplastic large-cell lymphoma and T-LBL. In
      contrast, cases belonging to the broad category of 'PTCL, unspecified' (PTCL-U)
      did not share a single molecular profile. Using a multiclass predictor, we could
      separate PTCL-U into three molecular subgroups called U1, U2 and U3. The U1 gene
      expression signature included genes known to be associated with poor outcome in
      other tumors, such as CCND2. The U2 subgroup was associated with overexpression
      of genes involved in T-cell activation and apoptosis, including NFKB1 and BCL-2.
      The U3 subgroup was mainly defined by overexpression of genes involved in the
      IFN/JAK/STAT pathway. It comprised a majority of histiocyte-rich PTCL samples.
      Gene Ontology annotations revealed different functional profile for each
      subgroup. These results suggest the existence of distinct subtypes of PTCL-U with
      specific molecular profiles, and thus provide a basis to improve their
      classification and to develop new therapeutic targets.

PMID- 16288227
TI  - Defensive dentistry.

PMID- 16288228
TI  - Cinderella of the NHS?

PMID- 16288229
TI  - Manpower problems.

PMID- 16288226
TI  - Oxidative metabolism of linoleic acid modulates PPAR-beta/delta suppression of
      PPAR-gamma activity.
AB  - Peroxisome proliferator-activated receptors (PPARs) are transcription factors
      that strongly influence molecular events in normal and cancer cells. PPAR
      beta/delta (PPAR-b/d) overexpression suppresses the activity of PPAR-gamma (PPAR
      g) and PPAR-alpha. This interaction has been questioned, however, by studies with
      synthetic ligands of PPARs in PPAR-b/d-null cells, and it is not known whether an
      interaction between PPAR-b/d and PPAR-g exists, especially in relation to the
      signaling by natural PPAR ligands. Oxidative metabolites of linoleic and
      arachidonic acids are natural ligands of PPARs. 13-S-hydroxyoctadecadienoic acid
      (13-S-HODE), the main product of 15-lipoxygenase-1 (15-LOX-1) metabolism of
      linoleic acid, downregulates PPAR-b/d. We tested (a) whether PPAR-b/d expression
      modulates PPAR-g activity in experimental models of the loss and gain of PPAR-b/d
      function in colon cancer cells and (b) whether 15-LOX-1 formation of 13-S-HODE
      influences the interaction between PPAR-b/d and PPAR-g. We found that (a) 15-LOX
      1 formation of 13-S-HODE promoted PPAR-g activity, (b) PPAR-b/d expression
      suppressed PPAR-g activity in models of both loss and gain of PPAR-b/d function,
      (c) 15-LOX-1 activated PPAR-g by downregulating PPAR-b/d, and (d) 15-LOX-1
      expression induced apoptosis in colon cancer cells via modulating PPAR-b/d
      suppression of PPAR-g. These findings elucidate a novel mechanism of the
      signaling by natural ligands of PPARs, which involves modulating the interaction
      between PPAR-b/d and PPAR-g.

PMID- 16288230
TI  - Dental treatment and CJD risk.

PMID- 16288231
TI  - Five-step definition.

PMID- 16288232
TI  - Legality and ethics.

PMID- 16288233
TI  - Ruth Ellis's dentist.

PMID- 16288234
TI  - Contempt for the Welsh.

PMID- 16288235
TI  - Death row dentistry.

PMID- 16288244
TI  - Reducing treatment side effects for head and neck cancer.

PMID- 16288248
TI  - Financing student education in the future.
AB  - Funding arrangements for university students entering courses will undergo a
      major change from 2006. From that date, universities will be able to charge
      students up to pounds 3,000 in tuition fees as a contribution to their education.
      Dental students may be disproportionately affected by the resulting debt because
      they will have less opportunity than those in other courses to earn money during
      a long summer vacation. In addition, dental and medical courses are longer in
      duration than the typical three year British degree course. We have outlined the
      major changes in these funding arrangements. Drawing on our experience in the
      United States and elsewhere in the world, we suggest that further large increases
      in university tuition fees seem inevitable. A major consequence of rising student
      debt may be denial of entry into the dental profession of the more disadvantaged
      in our community. Urgent research and planning needs to be done in advance so
      that this unpleasant scenario is prevented.

PMID- 16288249
TI  - Oral Medicine--update for the dental practitioner: oral white patches.
AB  - This series provides an overview of current thinking in the more relevant areas
      of oral medicine for primary care practitioners, written by the authors while
      they were holding the Presidencies of the European Association for Oral Medicine
      and the British Society for Oral Medicine, respectively. A book containing
      additional material will be published. The series gives the detail necessary to
      assist the primary dental clinical team caring for patients with oral complaints
      that may be seen in general dental practice. Space precludes inclusion of
      illustrations of uncommon or rare disorders, or discussion of disorders affecting
      the hard tissues. Approaching the subject mainly by the symptomatic approach--as
      it largely relates to the presenting complaint--was considered to be a more
      helpful approach for GDPs rather than taking a diagnostic category approach. The
      clinical aspects of the relevant disorders are discussed, including a brief
      overview of the aetiology, detail on the clinical features and how the diagnosis
      is made. Guidance on management and when to refer is also provided, along with
      relevant websites which offer further detail.

PMID- 16288257
TI  - Ivory tower derision.

PMID- 16288250
TI  - The European vibration directive--how will it affect the dental profession?
AB  - On 6 July 2005, the EU Physical Agents (Vibration) Directive (2002) came into
      force across all member states. This will mean that legally enforceable limits on
      hand-arm vibration exposures will be introduced and that risk management must be
      set in place at work. This article briefly describes the content of the
      Directive, how this will affect the dental profession and what measures will be
      required to ensure compliance.

PMID- 16288258
TI  - Grapefruit guidance.

PMID- 16288259
TI  - At risk individuals.

PMID- 16288260
TI  - Cysts: liquid content.

PMID- 16288261
TI  - A popular misconception.

PMID- 16288262
TI  - The effect of a mandibular advancement splint in subjects with sleep-related
      breathing disorders.
AB  - OBJECTIVE: This study assessed the effectiveness of a mandibular advancement
      splint (MAS) in subjects with sleep-related breathing disorders using both
      objective and subjective outcome measures. DESIGN: The study was carried out as a
      retrospective analysis. SETTING: The study was conducted within the Sleep Studies
      Unit at the Queen Victoria Hospital, East Grinstead, between May 1997 and March
      2000. SUBJECTS AND METHODS: Twenty subjects with obstructive sleep apnoea (OSA)
      and six with non-apnoeic snoring, diagnosed by overnight polysomnography, were
      fitted with a monobloc appliance between May 1997 and March 2000. MAIN OUTCOME
      MEASURES: The subjects were analysed for changes in the respiratory disturbance
      index (RDI) and Epworth Sleepiness Scale (ESS) scores. In addition each subject
      completed an outcome questionnaire following fitting of the appliance. RESULTS:
      Variability in response measured by the change in the respiratory disturbance
      index was found with no correlation to the baseline recording. Although median
      RDI values improved in both groups, significantly so in the obstructive sleep
      apnoea group (p<0.05), seven subjects exhibited an increased RDI score following
      mandibular advancement splint therapy. The median Epworth Sleepiness Scale scores
      decreased in both the OSA group and the non-apnoeic snorers although not
      significantly. Twenty-one of the 26 subjects completed the outcome questionnaire
      revealing an 81% reduction in snoring. Side-effects were generally transient and
      minor. Eighty-six per cent of the subjects' partners reported better quality of
      sleep as a result of MAS therapy. CONCLUSIONS: The monobloc appliance
      significantly improved the Respiratory Disturbance Index in the obstructive sleep
      apnoea group. Some subjects had increased RDI scores following splint therapy.
      This supports the need for an objective assessment in the follow-up of patients
      treated with mandibular advancement splints.

PMID- 16288263
TI  - Measuring access to health services: General Dental Services in Scotland.
AB  - OBJECTIVE: Recently the issue of access to health services has been brought into
      sharp focus by clear evidence of rationing--patients queuing for NHS registration
      -in the NHS General Dental Services (GDS). Conventional estimates suggest that
      about 50% of adults are registered per annum. This paper demonstrates that these
      conventional measures of access and utilisation can generate potentially
      misleading inferences. DESIGN: By analysing individual-level claims data from
      over 35,000 patients over six years we are able to: identify the underlying
      patterns of utilisation that generate the aggregate 50% registration rate;
      provide more detailed estimates of utilisation and access; and suggest possible
      determinants of the patterns of utilisation we observe. SETTING: Primary care
      health services. RESULTS: In contrast to conventional estimates of access we find
      that close to 80% of the adult population in Scotland has had access to GDS over
      a six year period. Moreover, we find that the population is comprised of a
      relatively large group of patients (30% of the population) who access GDS at
      least once a year and a substantial group (19% of the adult population) who
      access services only once in six years. The groups who access services at
      intermediate frequencies are less numerous. CONCLUSIONS: Assessing the
      effectiveness of the public provision of health care services requires accurate
      information regarding access to those services. This paper sets out a framework
      for analysing and interpreting longitudinal data to provide information on the
      extent of access to health care services.

PMID- 16288264
TI  - Pierre Fauchard and his role in the development of obturators.
AB  - The design and fabrication of oral appliances to replace parts of the palate
      missing due to congenital defects or lost through tumours, infection or trauma
      has been a considerable challenge for clinicians throughout the history of
      dentistry. Significant advances were made during the eighteenth century towards
      resolving the problem of constructing satisfactory obturators by the first
      'surgeon-dentist', Pierre Fauchard. This paper reviews his innovative designs.

PMID- 16288277
TI  - 125 years of developments in dentistry, 1880-2005. Part 4: clinical dentistry.

PMID- 16288280
TI  - AIDS restriction HLA allotypes target distinct intervals of HIV-1 pathogenesis.
AB  - An effective acquired immune response to infectious agents mediated by HLA
      restricted T-cell recognition can target different stages of disease
      pathogenesis. We show here that three distinct HLA alleles known to alter the
      overall rate of AIDS progression act during distinct intervals after HIV-1
      infection. The discrete timing of HLA allele influence suggests alternative
      functional mechanisms in immune defense against this dynamic and chronic
      immunosuppressive disease.

PMID- 16288281
TI  - Stem cells in the hair follicle bulge contribute to wound repair but not to
      homeostasis of the epidermis.
AB  - The discovery of long-lived epithelial stem cells in the bulge region of the hair
      follicle led to the hypothesis that epidermal renewal and epidermal repair after
      wounding both depend on these cells. To determine whether bulge cells are
      necessary for epidermal renewal, here we have ablated these cells by targeting
      them with a suicide gene encoding herpes simplex virus thymidine kinase (HSV-TK)
      using a Keratin 1-15 (Krt1-15) promoter. We show that ablation leads to complete
      loss of hair follicles but survival of the epidermis. Through fate-mapping
      experiments, we find that stem cells in the hair follicle bulge do not normally
      contribute cells to the epidermis which is organized into epidermal proliferative
      units, as previously predicted. After epidermal injury, however, cells from the
      bulge are recruited into the epidermis and migrate in a linear manner toward the
      center of the wound, ultimately forming a marked radial pattern. Notably,
      although the bulge-derived cells acquire an epidermal phenotype, most are
      eliminated from the epidermis over several weeks, indicating that bulge stem
      cells respond rapidly to epidermal wounding by generating short-lived 'transient
      amplifying' cells responsible for acute wound repair. Our findings have
      implications for both gene therapy and developing treatments for wounds because
      it will be necessary to consider epidermal and hair follicle stem cells as
      distinct populations.

PMID- 16288282
TI  - Host-reactive CD8+ memory stem cells in graft-versus-host disease.
AB  - Graft-versus-host disease (GVHD) is caused by alloreactive donor T cells that
      trigger host tissue injury. GVHD develops over weeks or months, but how this
      immune response is maintained over time is unknown. In mouse models of human
      GVHD, we identify a new subset of postmitotic CD44(lo)CD62L(hi)CD8(+) T cells
      that generate and sustain all allogeneic T-cell subsets in GVHD reactions,
      including central memory, effector memory and effector CD8(+) T cells, while self
      renewing. These cells express Sca-1, CD122 and Bcl-2, and induce GVHD upon
      transfer into secondary recipients. The postmitotic CD44(lo)CD62L(hi)CD8(+) T
      cells persist throughout the course of GVHD, are generated in the initial phase
      in response to alloantigens and dendritic cells and require interleukin-15. Thus,
      their long life, ability to self-renew and multipotentiality define these cells
      as candidate memory stem cells. Memory stem cells will be important targets for
      understanding and influencing diverse chronic immune reactions, including GVHD.

PMID- 16288285
TI  - AKT signaling in normal and malignant cells.
AB  - AKT/protein kinase B (PKB) is a cardinal node in diverse signaling cascades
      important in both normal cellular physiology and various disease states. AKT
      signaling regulates cell proliferation and survival, cell growth (size), glucose
      metabolism, cell motility and angiogenesis. Aberrant regulation of these
      processes result in cellular perturbations considered hallmarks of cancer, and
      numerous studies testify to the frequent hyperactivation of AKT signaling in many
      human cancers. Various oncoproteins and tumor suppressors intersect the AKT
      signal transduction pathway and are activated or inactivated, respectively, in
      cancer. This issue of Oncogene Reviews includes a collection of perspectives on
      the normal cellular functions of various components of the AKT pathway, as well
      as biological consequences of alterations of these proteins as related to
      tumorigenesis. Two reviews focus on AKT regulation, one of which addresses
      various aspects of phosphoinositide metabolism, while the other emphasizes the
      role of AKT-interacting proteins in AKT activation. Several reviews highlight the
      role of major AKT substrates involved in cellular metabolism, transcription and
      translation; another focuses on the role of AKT signaling in epithelial
      mesenchymal transition. Also included are articles on the involvement of AKT
      pathway deregulation in human cancer and certain hereditary cancer syndromes, as
      well as in murine models of cancer based on AKT pathway activation. Additional
      articles discuss current approaches to identify selective inhibitors of the AKT
      pathway.

PMID- 16288283
TI  - Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent
      antitumor immunity.
AB  - The immune system can act as an extrinsic suppressor of tumors. Therefore, tumor
      progression depends in part on mechanisms that downmodulate intrinsic immune
      surveillance. Identifying these inhibitory pathways may provide promising targets
      to enhance antitumor immunity. Here, we show that Stat3 is constitutively
      activated in diverse tumor-infiltrating immune cells, and ablating Stat3 in
      hematopoietic cells triggers an intrinsic immune-surveillance system that
      inhibits tumor growth and metastasis. We observed a markedly enhanced function of
      dendritic cells, T cells, natural killer (NK) cells and neutrophils in tumor
      bearing mice with Stat3(-/-) hematopoietic cells, and showed that tumor
      regression requires immune cells. Targeting Stat3 with a small-molecule drug
      induces T cell- and NK cell-dependent growth inhibition of established tumors
      otherwise resistant to direct killing by the inhibitor. Our findings show that
      Stat3 signaling restrains natural tumor immune surveillance and that inhibiting
      hematopoietic Stat3 in tumor-bearing hosts elicits multicomponent therapeutic
      antitumor immunity.

PMID- 16288286
TI  - Class reunion: PTEN joins the nuclear crew.
AB  - Several recent reports have brought conclusive evidence that the tumor suppressor
      PTEN, once considered a strictly cytoplasmic protein, shuttles to the nuclear
      compartment, where it joins a variety of components of the same pathway it
      regulates in the cytoplasm, among which PI3K, PDK1 and AKT. In this review, we
      focus on the growing supporting evidence for an important physiological role of
      this nuclear pathway and on the role that alteration of this novel regulatory
      circuit may play during cell transformation.

PMID- 16288287
TI  - Regulation of the Akt kinase by interacting proteins.
AB  - Ten years ago, it was observed that the Akt kinase is activated by
      phosphorylation via a phosphoinositide 3-kinase (PI-3K)-dependent process. This
      discovery generated enormous interest because it provided a link between PI-3K,
      an enzyme known to play a critical role in cellular physiology, and its
      downstream targets. Subsequently, it was shown that the activity of the core
      components of the 'PI-3K/Akt pathway' is modulated by a complex network of
      regulatory proteins and pathways. Some of the Akt-binding partners modulate its
      activation by external signals by interacting with different domains of the Akt
      protein. This review focuses on the Akt interacting proteins and the mechanisms
      by which they regulate Akt activation.

PMID- 16288288
TI  - FOXO transcription factors at the interface between longevity and tumor
      suppression.
AB  - A wide range of human diseases, including cancer, has a striking age-dependent
      onset. However, the molecular mechanisms that connect aging and cancer are just
      beginning to be unraveled. FOXO transcription factors are promising candidates to
      serve as molecular links between longevity and tumor suppression. These factors
      are major substrates of the protein kinase Akt. In the presence of insulin and
      growth factors, FOXO proteins are relocalized from the nucleus to the cytoplasm
      and degraded via the ubiquitin-proteasome pathway. In the absence of growth
      factors, FOXO proteins translocate to the nucleus and upregulate a series of
      target genes, thereby promoting cell cycle arrest, stress resistance, or
      apoptosis. Stress stimuli also trigger the relocalization of FOXO factors into
      the nucleus, thus allowing an adaptive response to stress stimuli. Consistent
      with the notion that stress resistance is highly coupled with lifespan extension,
      activation of FOXO transcription factors in worms and flies increases longevity.
      Emerging evidence also suggests that FOXO factors play a tumor suppressor role in
      a variety of cancers. Thus, FOXO proteins translate environmental stimuli into
      changes in gene expression programs that may coordinate organismal longevity and
      tumor suppression.

PMID- 16288289
TI  - The Akt of translational control.
AB  - The oncogene AKT (also called protein kinase B (PKB)) signals to the
      translational machinery, and activation of protein synthesis by Akt is associated
      with cancer formation. Akt directly stimulates the activity of translation
      initiation factors and upregulates ribosome biogenesis. Activation of protein
      synthesis by Akt is phylogenetically conserved from Drosophila to humans, and is
      important for regulating cell growth, proliferation and cell survival.
      Consequently, translation defects due to aberrant Akt activation may be a crucial
      mechanism leading to tumorigenesis. However, few in vivo studies have established
      a causative role for aberrant protein synthesis control in cancer. A major
      challenge in the future will be to identify the specific mRNAs regulated at the
      level of translation control directly relevant for cellular transformation. In
      this review, we highlight and discuss the emerging molecular and genetic evidence
      that support a model by which deregulation of specific or global protein
      synthesis contributes to cancer.

PMID- 16288290
TI  - Akt-dependent transformation: there is more to growth than just surviving.
AB  - Activation of the Akt/PKB protein kinase family triggers increases in cell size,
      metabolism and survival. Akt coordinately regulates these fundamental cellular
      processes through phosphorylation-dependent inactivation of tumor suppressors and
      activation of trophic signaling. Akt signaling stimulates transport and
      metabolism of both glucose and amino acids, which in turn support mTOR-dependent
      increases in protein translation. In addition, Akt activation directs cells to
      undertake a metabolic conversion from oxidative phosphorylation to aerobic
      glycolysis. Although this conversion promotes cell growth, it also renders cell
      survival dependent on a continuous supply of extracellular nutrients, which
      themselves are required regulatory elements in Akt signal transduction.

PMID- 16288291
TI  - Epithelial-mesenchymal transition in development and cancer: role of
      phosphatidylinositol 3' kinase/AKT pathways.
AB  - Epithelial-mesenchymal transition (EMT) is an important process during
      development by which epithelial cells acquire mesenchymal, fibroblast-like
      properties and show reduced intercellular adhesion and increased motility.
      Accumulating evidence points to a critical role of EMT-like events during tumor
      progression and malignant transformation, endowing the incipient cancer cell with
      invasive and metastatic properties. Several oncogenic pathways (peptide growth
      factors, Src, Ras, Ets, integrin, Wnt/beta-catenin and Notch) induce EMT and a
      critical molecular event is the downregulation of the cell adhesion molecule E
      cadherin. Recently, activation of the phosphatidylinositol 3' kinase (PI3K)/AKT
      axis is emerging as a central feature of EMT. In this review, we discuss the role
      of PI3K/AKT pathways in EMT during development and cancer with a focus on E
      cadherin regulation. Interactions between PI3K/AKT and other EMT-inducing
      pathways are presented, along with a discussion of the therapeutic implications
      of modulating EMT in order to achieve cancer control.

PMID- 16288293
TI  - Akt-regulated pathways in prostate cancer.
AB  - Prostate cancer remains a major cause of cancer-related mortality. Genetic clues
      to the molecular pathways driving the most aggressive forms of prostate cancer
      have been limited. Genetic inactivation of PTEN through either gene deletion or
      point mutation is reasonably common in metastatic prostate cancer and the
      resulting activation of phosphoinostide 3-kinase, AKT and mTOR provides a major
      therapeutic opportunity in this disease as mTOR inhibitors, HSP90 inhibitors and
      PI3K inhibitors begin to enter clinical development.

PMID- 16288292
TI  - Perturbations of the AKT signaling pathway in human cancer.
AB  - AKT/PKB (protein kinase B) kinases mediate signaling pathways downstream of
      activated tyrosine kinases and phosphatidylinositol 3-kinase. AKT kinases
      regulate diverse cellular processes including cell proliferation and survival,
      cell size and response to nutrient availability, tissue invasion and
      angiogenesis. Many oncoproteins and tumor suppressors implicated in cell
      signaling/metabolic regulation converge within the AKT signal transduction
      pathway in an equilibrium that is altered in many human cancers by activating and
      inactivating mechanisms, respectively, targeting these inter-related proteins. We
      review a burgeoning literature implicating aberrant AKT signaling in many
      sporadic human cancers as well as in several dominantly inherited cancer
      syndromes known as phakomatoses. The latter include disorders caused by germline
      mutations of certain tumor suppressor genes, that is, PTEN, TSC2/TSC1, LKB1, NF1,
      and VHL, encoding proteins that intersect with the AKT pathway. We also review
      various pathogenic mechanisms contributing to activation of the AKT pathway in
      human malignancy as well as current pharmacologic strategies to target
      therapeutically components of this pathway.

PMID- 16288294
TI  - Tuberous sclerosis complex: linking growth and energy signaling pathways with
      human disease.
AB  - The most exciting advances in the tuberous sclerosis complex (TSC) field occurred
      in 1993 and 1997 with the cloning of the TSC2 and TSC1 genes, respectively, and
      in 2003 with the identification of Rheb as the target of tuberin's (TSC2) GTPase
      activating protein (GAP) domain. Rheb has a dual role: it activates mTOR and
      inactivates B-Raf. Activation of mTOR leads to increased protein synthesis
      through phosphorylation of p70S6K and 4E-BP1. Upon insulin or growth factor
      stimulation, tuberin is phosphorylated by several kinases, including AKT/PKB,
      thereby suppressing its GAP activity and activating mTOR. Phosphorylation of
      hamartin (TSC1) by CDK1 also negatively regulates the activity of the
      hamartin/tuberin complex. Despite these biochemical advances, exactly how
      mutations in TSC1 or TSC2 lead to the clinical manifestations of TSC is far from
      being understood. Two of the most unusual phenotypes in TSC are the apparent
      metastasis of benign cells carrying TSC1 and TSC2 mutations, resulting in
      pulmonary lymphangiomyomatosis, and the ability of cells with TSC1 or TSC2
      mutations to differentiate into the separate components of renal angiomyolipomas
      (vessels, smooth muscle and fat). We will discuss how the TSC signaling pathways
      are affected by mutations in TSC1 or TSC2, focusing on how these mutations may
      lead to the renal and pulmonary manifestations of TSC.

PMID- 16288295
TI  - The Akt/PKB pathway: molecular target for cancer drug discovery.
AB  - The serine/threonine kinase Akt/PKB pathway presents an exciting new target for
      molecular therapeutics, as it functions as a cardinal nodal point for transducing
      extracellular (growth factor and insulin) and intracellular (receptor tyrosine
      kinases, Ras and Src) oncogenic signals. In addition, alterations of the Akt
      pathway have been detected in a number of human malignancies. Ectopic expression
      of Akt, especially constitutively activated Akt, is sufficient to induce
      oncogenic transformation of cells and tumor formation in transgenic mice as well
      as chemoresistance. Akt has a wide range of downstream targets that regulate
      tumor-associated cell processes such as cell growth, cell cycle progression,
      survival, migration, epithelial-mesenchymal transition and angiogenesis. Blockage
      of Akt signaling results in apoptosis and growth inhibition of tumor cells with
      elevated Akt. The observed dependence of certain tumors on Akt signaling for
      survival and growth has wide implications for cancer therapy, offering the
      potential for preferential tumor cell killing. In the last several years, through
      combinatorial chemistry, high-throughput and virtual screening, and traditional
      medicinal chemistry, a number of inhibitors of the Akt pathway have been
      identified. This review focuses on ongoing translational efforts to
      therapeutically target the Akt pathway.

PMID- 16288296
TI  - AKT crystal structure and AKT-specific inhibitors.
AB  - AKT kinases are attractive targets for small molecule drug discovery because of
      their key role in tumor cell survival/proliferation and their
      overexpression/activation in many human cancers. This review summarizes studies
      that support the rationale for targeting AKT kinases in new drug discovery
      efforts. Structural features of AKT kinase in its inactive and active states, as
      determined by crystal structure analysis, are described. Recent efforts in the
      development and biological evaluation of small molecule inhibitors of AKT, and
      the challenges remaining are summarized. Inhibitors targeting the ATP binding
      site, PH domain and protein substrate binding site, as well as isoform selective
      allosteric inhibitors are reviewed. Structure-based design using PKA mutants as
      surrogates and computer modeling in the discovery of selective inhibitors is
      discussed. The issues and challenges facing the development of different classes
      of inhibitors as therapeutics are also discussed.

PMID- 16288297
TI  - Metalloproteinases: mediators of pathology and regeneration in the CNS.
AB  - The matrix metalloproteinases and related A disintegrin and metalloproteinase
      enzymes are implicated in various diseases of the nervous system. However,
      metalloproteinases are increasingly being recognized as having beneficial roles
      during nervous system development and following injury. This review discusses
      general principles that govern the expression of metalloproteinases in the
      nervous system and their detrimental outcomes. It then focuses on the roles of
      metalloproteinases and their mechanisms in regulating neurogenesis, myelin
      formation and axonal growth. It is clear that metalloproteinases are important
      determinants in enabling recovery from injury to the nervous system.

PMID- 16288298
TI  - Normal huntingtin function: an alternative approach to Huntington's disease.
AB  - Several neurological diseases are characterized by the altered activity of one or
      a few ubiquitously expressed cell proteins, but it is not known how these normal
      proteins turn into harmful executors of selective neuronal cell death. We
      selected huntingtin in Huntington's disease to explore this question because the
      dominant inheritance pattern of the disease seems to exclude the possibility that
      the wild-type protein has a role in the natural history of this condition.
      However, even in this extreme case, there is considerable evidence that normal
      huntingtin is important for neuronal function and that the activity of some of
      its downstream effectors, such as brain-derived neurotrophic factor, is reduced
      in Huntington's disease.

PMID- 16288299
TI  - Exuberance in the development of cortical networks.
AB  - The cerebral cortex is the largest and most intricately connected part of the
      mammalian brain. Its size and complexity has increased during the course of
      evolution, allowing improvements in old functions and causing the emergence of
      new ones, such as language. This has expanded the behavioural and cognitive
      repertoire of different species and has determined their competitive success. To
      allow the relatively rapid emergence of large evolutionary changes in a structure
      of such importance and complexity, the mechanisms by which cortical circuitry
      develops must be flexible and yet robust against changes that could disrupt the
      normal functions of the networks.

PMID- 16288300
TI  - Overall obesity, abdominal adiposity, diabetes and cigarette smoking in relation
      to the risk of pancreatic cancer in two Swedish population-based cohorts.
AB  - We examined the associations of body mass index (BMI), waist circumference, a
      history of diabetes, and cigarette smoking with risk of pancreatic cancer among
      37,147 women and 45,906 men followed up during 560,666 person-years in the
      Swedish Mammography Cohort and the Cohort of Swedish Men; 136 incident cases of
      pancreatic cancer were diagnosed. The multivariate rate ratio (RR) of pancreatic
      cancer for obese women and men (BMI > or =30 kg/m(2)) was 1.81 (95% CI: 1.04
      3.15) compared to those with a BMI of 20-25 kg/m(2). For a difference of 20 cm
      (about two standard deviations) in waist circumference, the multivariate RRs were
      1.32 (95% CI: 0.73-2.37) among women and 1.74 (95% CI: 1.00-3.01) among men.
      Pancreatic cancer risk was associated with history of diabetes (multivariate RR:
      1.88; 95% CI: 1.09-3.26) and cigarette smoking (multivariate RR for current
      compared with never smokers: 3.06; 95% CI: 1.99-4.72). Current smokers of > or
      =40 pack-years had a five-fold elevated risk compared with never smokers. Risk
      among past smokers approached the RR for never smokers within 5-10 years
      following smoking cessation. Findings from this prospective study support
      positive relationships of overall obesity, abdominal adiposity, diabetes and
      smoking with risk of pancreatic cancer.

PMID- 16288301
TI  - Association of childhood acute lymphoblastic leukaemia with cancers in family
      members.
AB  - Children whose twins have had leukaemia have a higher risk of contracting acute
      lymphoblastic leukaemia (ALL), confirming a prenatal origin of the disease. This
      association was not true when considering other types of affected first-degree
      relatives. Children whose fathers were diagnosed with testicular cancer have a
      higher risk of ALL.

PMID- 16288302
TI  - A phase I/II trial of irinotecan-cisplatin combined with an anti-late-diarrhoeal
      programme to evaluate the safety and antitumour response of this combination
      therapy in patients with advanced non-small-cell lung cancer.
AB  - We conducted a phase I/II study in patients with advanced non-small-cell lung
      cancer (NSCLC) to increase the therapeutic index of the cisplatin-irinotecan
      combination by institution of an anti-late-diarrhoeal program (ADP). A total of
      77 chemotherapy-naive patients with advanced NSCLC were enrolled. The cisplatin
      dose was fixed at 60 mg m(-2) (Day 1). Irinotecan was escalated in 5 mg m(-2)
      increments, starting from 60 mg m(-2) (Days 1 and 8). ADP consisted of oral
      sodium bicarbonate, magnesium oxide, basic water, and ursodeoxycholic acid, and
      was administered orally for 4 days with each dose of irinotecan. In the phase I
      portion, irinotecan pharmacokinetics was also examined. After the recommended
      dose of irinotecan with ADP was determined, a phase II study was conducted to
      evaluate the response. Maximum tolerated dose was reached at an irinotecan dose
      of 80 mg m(-2) (Grade 4 diarrhoea and neutropenia). Pharmacokinetic studies show
      that the maximum concentration and the area under the curve of both irinotecan
      and SN38 (active metabolite of irinotecan) tend to increase in the dose-dependent
      manner of irinotecan. The phase II portion of the study included 48 patients, who
      were treated with 75 mg m(-2) of irinotecan. Grade 3/4 toxicities included
      neutropenia in 65%, leucopenia in 33%, and late diarrhoea in 6% of the patients.
      During this treatment, PS did not change in 65% of patients. At the end of the
      chemotherapy, PS did not decline in 90% of patients. In the phase II portion, a
      response occurred in 63% (95% confidential interval (CI), 47-76%) of patients.
      Median time to progression was 19 weeks (95% CI, 15-22 weeks), and median
      survival was 52 weeks (95% CI, 39-64 weeks). This regimen of irinotecan and
      cisplatin with ADP resulted in promising efficacy with acceptable toxicity for
      patients with advanced NSCLC. This regimen is a candidate for the experimental
      arm towards future phase III studies.

PMID- 16288303
TI  - HER3 genomic gain and sensitivity to gefitinib in advanced non-small-cell lung
      cancer patients.
AB  - In non-small-cell lung cancer (NSCLC), sensitivity to tyrosine kinase inhibitors
      (TKIs) is associated with activating mutations and genomic gain of the epidermal
      growth factor receptor (EGFR). Preclinical data suggested that HER3
      overexpression increases sensitivity to TKIs. A total of 82 NSCLC patients
      treated with gefitinib (250 mg), and previously evaluated for EGFR and HER2
      status by fluorescence in situ hybridisation (FISH) and DNA sequencing, and for
      Phospho-Akt status by immunohistochemistry, were investigated for HER3 genomic
      gain by FISH. Patients with high polysomy and gene amplification were considered
      as HER3 FISH positive (+). HER3 FISH+ pattern was significantly associated with
      female gender (P=0.02) and never smoking history (P=0.02). Patients with HER3+
      tumours (26.8%) had a significantly longer time to progression (3.7 vs 2.7,
      P=0.04) than patients with HER3- tumours, but not a significantly better response
      rate or survival. Patients with EGFR+/HER3+ tumours had higher objective response
      rate (36.4 vs 9.9%, P=0.03) and time to progression (7.7 vs 2.7 months, P=0.03)
      than patients with EGFR- and/or HER3- tumours, but no significantly longer
      survival. No difference in response was observed according to HER3 status in
      patients with EGFR+ tumours. Patients with HER2+/HER3+ tumours had similar
      outcome as patients with HER2- and/or HER3- tumours. Significantly different
      clinical end points were not observed between patients with HER3+/P-Akt+ and HER3
      and/or P-Akt- tumours. Genomic gain for HER3 is not a marker for response or
      resistance to TKI therapy in advanced NSCLC patients.

PMID- 16288306
TI  - Mouse models: psoriasis: an epidermal disease after all?

PMID- 16288304
TI  - Elevated phosphorylation and activation of PDK-1/AKT pathway in human breast
      cancer.
AB  - Activation of kinases signalling pathways contributes to various malignant
      phenotypes in human cancers, including breast tumour. To examine the possible
      activation of these signalling molecules, we examined the phosphorylation status
      in 12 protein kinases and transcription factors in normal primary human mammary
      epithelial cells, telomerase-immortalised human breast epithelial cell line, and
      two breast cancer lines, MDA-MB-468 and MCF-7, using Kinexus phosphorylated
      protein screening assays. The phosphorylation of FAK, mTOR, p70S6K, and PDK-1
      were elevated in both breast cancer cell lines, whereas the phosphorylation of
      AKT, EGFR, ErbB2/Her2, PDGFR, Shc, and Stat3 were elevated in only one breast
      cancer line compared to normal primary mammary epithelial cells and telomerase
      immortalised breast epithelial cells. The same findings were confirmed by Western
      blotting and by kinase assays. We further substantiated the phosphorylation
      status of these molecules in tissue microarray slides containing 89 invasive
      breast cancer tissues as well as six normal mammary tissues with
      immunohistochemistry staining using phospho-specific antibodies. Consistent
      findings were obtained as greater than 70% of invasive breast carcinomas
      expressed moderate to high levels of phosphorylated PDK-1, AKT, p70S6K, and EGFR.
      In sharp contrast, phosphorylation of the same proteins was nearly undetectable
      or was at low levels in normal mammary tissues under the same assay. Elevated
      phosphorylation of PDK-1, AKT, mTOR, p70S6K, S6, EGFR, and Stat3 were highly
      associated with invasive breast tumours (P<0.05). Taken together, our results
      suggest that activation of these kinase pathways by phosphorylation may in part
      account for molecular pathogenesis of human breast carcinoma. Particularly,
      moderate to high level of PDK-1 phosphorylation was found in 86% of high-grade
      metastasised breast tumours. This is the first report demonstrating
      phosphorylation of PDK-1 is frequently elevated in breast cancer with
      concomitantly increased phosphorylation of downstream kinases, including AKT,
      mTOR, p70S6K, S6, and Stat3. This finding thus suggested PDK-1 may promote
      oncogenesis in part through the activation of AKT and p70S6K and rationalised
      that PDK-1 as well as downstream components of PDK-1 signalling pathway may be
      promising therapeutic targets to treat breast cancer.

PMID- 16288305
TI  - Human recombinant erythropoietin (rEpo) has no effect on tumour growth or
      angiogenesis.
AB  - Tumour hypoxia has been shown to increase mutation rate, angiogenesis, and
      metastatic potential, and decrease response to conventional therapeutics.
      Improved tumour oxygenation should translate into increased treatment response.
      Exogenous recombinant erythropoietin (rEpo) has been recently shown to increase
      tumour oxygenation in a mammary carcinoma model. The mechanism of this action is
      not yet understood completely. The presence of Epo and its receptor (EpoR) have
      been demonstrated on several normal and neoplastic tissues, including blood
      vessels and various solid tumours. In addition, rEpo has been shown in two recent
      prospective, randomized clinical trials to negatively impact treatment outcome.
      In this study, we attempt to characterize the direct effects of rEpo on tumour
      growth and angiogenesis in two separate rodent carcinomas. The effect of rEpo on
      R3230 rat mammary adenocarcinomas, CT-26 mouse colon carcinomas, HCT-116 human
      colon carcinomas, and FaDu human head and neck tumours, all of which express
      EpoR, was examined. There were no differences in tumour growth or proliferation
      (measured by Ki-67) between placebo-treated and rEpo-treated tumours. In the
      mammary window chamber, vascular length density (VLD) measurements in serial
      images of both placebo-treated and Epo-treated rats revealed no difference in
      angiogenesis between the Epo-treated tumours and placebo-treated tumours at any
      time point. These experiments are important because they suggest that the recent
      clinical detriment seen with the use of Epo is not due to its tumour growth
      effects or angiogenesis. These studies also suggest that further preclinical
      studies need to examine rEpo's direct tumour effects in efforts to improve the
      therapeutic benefits of Epo in solid tumour patients.

PMID- 16288307
TI  - Recent advances in array comparative genomic hybridization technologies and their
      applications in human genetics.
AB  - Array comparative genomic hybridization (array CGH) is a method used to detect
      segmental DNA copy number alterations. Recently, advances in this technology have
      enabled high-resolution examination for identifying genetic alterations and copy
      number variations on a genome-wide scale. This review describes the current
      genomic array platforms and CGH methodologies, highlights their applications for
      studying cancer genetics, constitutional disease and human variation, and
      discusses visualization and analytical software programs for computational
      interpretation of array CGH data.

PMID- 16288308
TI  - Cancer transcriptomics: modeling metastasis.

PMID- 16288309
TI  - Clock genes as a link between addiction and obesity.

PMID- 16288310
TI  - Genome-wide linkage scan for spontaneous DZ twinning.
AB  - In humans, spontaneous DZ twinning is known to have a genetic basis. A prior
      investigation in the Flemish and Dutch population showed that the phenotype of
      'having DZ twins' was consistent with an autosomal monogenic dominant model, with
      a gene frequency of 3.5% and a female-specific lifetime penetrance of 10%.
      Recessive, X-linked, polygenic and sporadic models were rejected. This study
      reports on a genome-wide scan of 14 Flemish families containing 57 mothers of
      spontaneous DZ twins. Two-point linkage analysis using the autosomal dominant
      model showed nine chromosomal regions with a LOD score around 1. After multipoint
      linkage analysis, including heterogeneity, three chromosomes continued to give
      high LOD scores. These regions were further haplotyped with additional markers at
      1 cM distance. The multipoint analysis was not in favour of linkage of the DZ
      twinning trait in most candidate genes and other regions (LOD score < -2) under
      the genetic model of autosomal dominance. To further evaluate the evidence for
      linkage given some uncertainty about the correct mode of inheritance of twinning
      susceptibility other models of inheritance were tested. Results of this analysis
      showed all models gave highest LOD scores under dominant models. If heterogeneity
      among the families is taken into account, the peaks that were observed on
      chromosome 2, 7 and 18 could well contain a potential gene contributing to DZ
      twinning. These results give suggestive evidence that the mode of inheritance of
      DZ twinning is probably more complex than was originally expected.

PMID- 16288312
TI  - Improving the accuracy of BRCA1/2 mutation prediction: validation of the novel
      country-customized IC software.
AB  - Inherited mutations of the BRCA1/2 genes confer a significantly increased risk
      for breast and/or ovarian cancer development. Several models were elaborated to
      help genetic counsellors in selecting individuals with high probability of being
      mutation carriers. The IC software, a country-customized version of the Brcapro
      model, was recently shown to be particularly accurate in the prediction of
      carrier probability status in the Italian population. Here, we used our
      independent series of 70 breast/ovarian cancer families to analyze the
      performances of the IC software and compare it to widely used models, such as
      Brcapro and the Myriad mutation prevalence tables. Analysis of the areas under
      the receiver operator characteristics (ROC) curves indicated that overall the
      models performed well. However, the IC software and Myriad tables were more
      efficient in predicting mutated cases, showing a higher sensitivity (94 and 88%,
      respectively) and negative predictive value (NPV, 94 and 92%, respectively)
      compared to Brcapro (sensitivity 71 and NPV 83%). IC software also appeared
      particularly accurate in the identification of families belonging the low
      mutation risk group (<10%). Finally, most Brcapro failures occurred in the
      hereditary breast cancer (HBC) family subset, and in 75% of the cases, the IC
      software corrected them. Our data suggest that the country-customized
      implementation operated on the Brcapro software generated a more accurate tool
      for the prediction of BRCA1/2 gene mutation. Whether the IC or other country
      customized models might improve BRCA1/2 mutation prediction also in non-Italian
      families needs to be further explored.

PMID- 16288313
TI  - Genome scan on Swedish Alzheimer's disease families.
AB  - Alzheimer's disease (AD) is an age-related disease, which affects approximately
      40% of the population at an age above 90 years. The heritability is estimated to
      be greater than 60% and there are rare autosomal dominant forms indicating a
      significant genetic influence on the disease process. Despite the successes in
      the early 1990s when four genes were identified, which directly cause the disease
      (APP, PSEN1 and PSEN2) or greatly increase the risk of disease development
      (APOE), it has proved exceedingly difficult to identify additional genes involved
      in the pathogenesis. However, several linkage and association studies have
      repeatedly supported the presence of susceptibility genes on chromosomes (chrms)
      9, 10 and 12. The study populations have, however, mostly been of great genetic
      heterogeneity, and this may have contributed to the meagre successes in
      identifying the disease associated genetic variants. In this study, we have
      performed a genome wide linkage study on 71 AD families from the relatively
      genetically homogeneous Swedish population where it is also possible to study the
      genetic ancestry in public databases. We have performed nonparametric linkage
      analyses in the total family material as well as stratified the families with
      respect to the presence or absence of APOE varepsilon4. Our results suggest that
      the families included in this study are tightly linked to the APOE region, but do
      not show evidence of linkage to the previously reported linkages on chrms 9, 10
      and 12. Instead, we observed the next highest LOD score on chromosome 5q35 in the
      total material. Further, the data suggest that the major fraction of families
      linked to this region is APOE varepsilon4 positive.

PMID- 16288314
TI  - The expression of proapoptosis genes is increased in bipolar disorder, but not in
      schizophrenia.
AB  - Post-mortem studies conducted over the past 15 years suggest that apoptosis could
      play a role in the pathophysiology of bipolar disorder (BD) and, to a lesser
      degree, schizophrenia (SZ). To test this hypothesis, we have performed a post hoc
      analysis of an extant gene expression profiling database obtained from the
      hippocampus using a novel methodology with improved sensitivity. Consistent with
      the working hypothesis, BDs showed a marked upregulation of 19 out of 44
      apoptosis genes; however, contrary to the hypothesis, the SZ group showed a
      downregulation of genes associated with apoptotic injury and death. These changes
      in the regulation of apoptosis genes were validated using quantitative RT-PCR.
      Additionally, antioxidant genes showed a marked downregulation in BDs, suggesting
      that accumulation of free radicals might occur in the setting of a previously
      reported decrease of the electron transport chain in this disorder. Overall, the
      changes seen in BDs and SZs do not appear to be related to exposure to either
      neuroleptics or mood stabilizers. We conclude that fundamental differences in the
      genetic regulation of apoptosis and antioxidant genes may help discriminate
      between the pathophysiology of BD and SZ and potentially point to new treatment
      strategies that are specific for each disorder.

PMID- 16288315
TI  - Evolutionary genetics: when duplicated genes don't stick to the rules.

PMID- 16288317
TI  - [Clinical and pathological aspects of some odontogenic tumors and related
      lesions].
AB  - The jaw bones are the most common sites for epithelial cysts and tumors in the
      human skeleton due to their close relationship to the tooth and odontogenesis.
      Most of these cysts and tumors have in common an origin from the tissues of tooth
      formation and constitute a very diverse group of lesions that reflects the
      complex development of the dental structures. This group of odontogenic lesions
      occurs predominantly in the jaws, with a predilection for young people. Some
      aggressive lesions have attracted much attention as they often produce marked
      facial deformity and tend to recur after insufficient surgery. The most widely
      quoted classification of odontogenic tumors is that proposed in the WHO booklet
      published in 1992. There are, however, a number of controversial issues that need
      to be addressed with respect to clinicopathological subtypings, terminology, and
      diagnosis which all have direct bearings on therapeutic and/or prognostic
      implications. In the light of recent publication of the WHO new classification
      and a series of related studies undertaken by the author's group, this paper is
      to put together an overview on some of these important aspects related to
      unicystic ameloblastoma, clear cell odontogenic tumor, calcifying odontogenic
      cyst, odontogenic keratocyst, ameloblastic fibroma and its related lesions.
      Consequent upon a better understanding of the nature of these tumors and their
      variants, the various treatment protocols currently recommended by different
      surgeons will be better rationalized.

PMID- 16288316
TI  - PM source apportionment and health effects. 3. Investigation of inter-method
      variations in associations between estimated source contributions of PM2.5 and
      daily mortality in Phoenix, AZ.
AB  - As part of an EPA-sponsored workshop to investigate the use of source
      apportionment in health effects analyses, the associations between the
      participant's estimated source contributions of PM(2.5) for Phoenix, AZ for the
      period from 1995-1997 and cardiovascular and total nonaccidental mortality were
      analyzed using Poisson generalized linear models (GLM). The base model controlled
      for extreme temperatures, relative humidity, day of week, and time trends using
      natural spline smoothers. The same mortality model was applied to all of the
      apportionment results to provide a consistent comparison across source components
      and investigators/methods. Of the apportioned anthropogenic PM(2.5) source
      categories, secondary sulfate, traffic, and copper smelter-derived particles were
      most consistently associated with cardiovascular mortality. The sources with the
      largest cardiovascular mortality effect size were secondary sulfate (median
      estimate=16.0% per 5th-to-95th percentile increment at lag 0 day among eight
      investigators/methods) and traffic (median estimate=13.2% per 5th-to-95th
      percentile increment at lag 1 day among nine investigators/methods). For total
      mortality, the associations were weaker. Sea salt was also found to be associated
      with both total and cardiovascular mortality, but at 5 days lag. Fine particle
      soil and biomass burning factors were not associated with increased risks.
      Variations in the maximum effect lag varied by source category suggesting that
      past analyses considering only single lags of PM(2.5) may have underestimated
      health impact contributions at different lags. Further research is needed on the
      possibility that different PM(2.5) source components may have different effect
      lag structure. There was considerable consistency in the health effects results
      across source apportionments in their effect estimates and their lag structures.
      Variations in results across investigators/methods were small compared to the
      variations across source categories. These results indicate reproducibility of
      source apportionment results across investigative groups and support
      applicability of these methods to effects studies. However, future research will
      also need to investigate a number of other important issues including accuracy of
      results.

PMID- 16288318
TI  - [The relationship between the calcaneus density and the degree of inflammation in
      patients with generalized aggressive periodontitis].
AB  - PURPOSE: To evaluate the relationship between the calcaneus density and the
      degree of inflammation in patients with generalized aggressive periodontitis.
      METHODS: Thirty one volunteers with healthy periodontium (as control group) and
      38 patients with generalized aggressive periodontitis (as experimental group)
      were involved in this study. The average ages of the two groups were 27 and 23
      years respectively. The clinical periodontal indexes and panoramic films were
      measured first. And the broadband ultrasonic attenuation(BUA) and T-score of the
      calcaneus were then determined using ultrasonic bone densitometer. SAS6.12
      software package was used to analyse the data obtained. RESULTS: The BUA values
      of the two groups were 62.76+/-4.61 and 70.47+/-4.41 respectively, the BUA value
      of the experimental group was significantly lower than that of the control group
      (P<0.001). Moreover, T-score was different between the two groups and the score
      in the experimental group was significantly lower than that in the control
      (P<0.001). CONCLUSIONS: The BUA and T-score in patients with generalized
      aggressive periodontitis were significantly lower than that in the controls with
      healthy periodontium, which indicated that patients with generalized aggressive
      periodontitis had overall bone density decrease.

PMID- 16288319
TI  - [Correlation study between sex and age of patients and root resorption after
      orthodontic treatment].
AB  - PURPOSE: To investigate the relationship between root resorption related to fixed
      appliance and the variables including sex, age. METHODS: 44 patients were divided
      into four groups according to sex and age: juvenile males, juvenile females,
      adult males, adult females. The length of incisors was calculated according to
      orthopantomograph and study models of pre- and post-treatment, and the
      relationship between patients' sex and age and root absorption pre- and post
      treatment was analyzed by paired t test. RESULTS: Root absorption occurred in
      every patient. There was no significant difference between the same-age groups of
      males and females (P<0.05); However, there was significant difference between
      adult groups (both males and females) and juvenile groups (P<0.01). CONCLUSION:
      Root absorption occurs in every fixed-appliance case. Fixed-appliance-caused root
      absorption has no significant correlation with sex;however, absorption of adult
      groups is of higher level than that of juvenile groups.

PMID- 16288320
TI  - [Design and application of the framework to prevent fracture of the magnetic
      denture].
AB  - PURPOSE: To investigate the methods to prevent magnetic denture from fracture.
      METHODS: 17 cases were selected and divided into group A and group B. 9 cases in
      group A only used resin base, 8 cases in group B were strengthened with
      frameworks. The rates of fracture or fissure in denture base were observed for 5
      years, Chi(2) test was used for statistical analysis. RESULTS: In group A, 3
      cases were found with damaged base, there was no fracture happened in group B.
      Chi(2) test showed that there was significant difference between the two groups
      (P<0.05). CONCLUSION: Frameworks should be designed to improve the strength of
      the magnetic denture base. It is easy to manufacture and apply with satisfactory
      clinical effects.

PMID- 16288321
TI  - [Clinical research of rehabilitating bilateral total maxillary defects with a new
      improved implants and magnetic attachments bar frameworks: report of 9 cases].
AB  - PURPOSE: The purpose of this study was to research the clinical effects of a new
      improved implant-magnetic attachment bar framework supported the total maxillary
      prosthesis. METHODS: Nine patients underwent tumor resection with defect of
      bilateral maxilla, and after at least 1 year,4 implants was inserted into their
      bilateral zygomatics in every patient. A kind of new improved bar framework were
      fabricated with implants tightly. Based on these bar framework ,total maxillary
      prostheses were completed finally. RESULTS: The new improved bar framework was
      utilized to support the prosthesis, it was observed that the prosthesis was more
      stable. All patients were satisfied with mastication, speech and appearance after
      wearing the prosthesis. The prosthesis demonstrated a significant improvement in
      function and esthetics. CONCLUSIONS: It is concluded that from the practical
      point of view,the prosthesis with new bar framework is superior to the previous
      one, and its clinical prosperity is wide. But further studies are necessary to
      evaluate its long term effects.

PMID- 16288322
TI  - [The research on maxillofacial soft tissue reconstruction by 3-D laser scanning].
AB  - PURPOSE: To evaluate the role of 3-D laser scanning on reconstruction of
      maxillofacial soft tissues. METHODS: 3-D laser scan was given to a patient who
      had his right ear absent and reconstruct the image. RESULTS: 3-D laser scanning
      can reconstruct facial soft tissue quickly and precisely, but the image of the
      ear was not very clear. CONCLUSION: In the living, laser scanning can reconstruct
      all the maxillofacial soft tissues except for the ear. It can be widely used in
      clinic and research.

PMID- 16288323
TI  - [Multivariate analysis of the prognostic factors in 230 surgically treated oral
      mucosal malignant melanomas].
AB  - PURPOSE: To analyze the prognostic factors which influence the survival rates in
      oral mucosal malignant melanoma patients. METHODS: 230 consecutive patients with
      oral mucosal malignant melanoma were included in the study. There were 141 males
      and 89 females.34 were in (TNM) I stage, 87 in II stage and 109 in III stage. Cox
      proportional hazards model was used to analyze the statistically significant
      prognostic factors. Kaplan-Meier method was used to analyze the survival rate
      under the different levels of the different factors and Log rank method for
      comparison of the distribution of the different survival rates. RESULTS: The
      prognostic factors include the thickness of the tumor, cervical lymph node
      metastasis, the presence or absence of ulceration and the anatomic sites. The P
      value and the relative risk were P<0.001, RR=1.868; P<0.001, RR=1.685; P<0.001,
      RR=1.411; P=0.008, RR=0.747, respectively. The different factors were independent
      with each other. The factors of sex (P=0.136), age (P=0.721) and the surgical
      method used (P=0.944) had no influence on survival rates in this study.
      CONCLUSIONS: The significant prognostic factors which influence the survival
      rates in oral mucosal malignant melanoma patients were similar to that in the
      skin malignant melanoma patients. The factors did not have factor-by-factor
      interactions. Surgery alone is not the best treatment of choice for oral mucosal
      melanoma.

PMID- 16288324
TI  - [Relationship between parents' attitude and children's oral health behavior].
AB  - PURPOSE: The purpose of this investigation was to study the relationship between
      parents' attitude toward caries risk factor and children's behavior, such as
      brushing behavior and sugar-intake behavior, to provide foundation in carrying
      out oral health education. METHODS: A case-control study was performed to analyze
      parents' attitude of caries and their relationship with children's behavior. The
      groups were as follows: control group(dmft=0) and case group(dmft> or =3). Data
      was processed with Logistic regression of SPSS10.0. RESULTS: It was found that
      parents' attitude toward children's brushing teeth and sugar-intake had strong
      correlation with children's behavior in daily life. CONCLUSIONS: The results
      support the concept that parents' attitude toward children's tooth brushing and
      sugar-intake can predict their children's behavior. Caries can be reduced through
      oral health education in parents.

PMID- 16288325
TI  - [Treatment of recurrent odontogenic keratocyst with enucleation and cryosurgery:
      a retrospective study of 10 cases].
AB  - PURPOSE: To evaluate the clinical outcomes of treatment of recurrent odontogenic
      keratocyst with enucleation and cryosurgery in 10 consecutive cases. METHODS: 10
      patients with recurrent odontogenic keratocyst of the jaw were treated with
      enucleation and liquid nitrogen cryosurgery between 1994 and 2000. After
      enucleation of the cystic lining, liquid nitrogen (-196 degrees C) was applied to
      the bony walls via cotton rolls for cryosurgery. The time for cryosurgery was
      between 3 to 5 minutes with 3 cycles of freeze and thaw. All the patients were
      followed up for 5 to 10 years after treatment with regular clinical and
      radiographic examinations. Postoperative complications and the final outcomes
      were evaluated. RESULTS: No recurrence was noted within the follow-up period
      after combined treatment of enucleation and cryosurgery. Secondary wound healing
      developed in 1 patient due to accidental freezing of the adjacent tissues, and
      pathologic fracture of the mandible occurred in 1 patient. The fracture healed
      secondarily with intermaxillary fixation. CONCLUSION: Based on these results, the
      combination of enucleation and liquid nitrogen cryotherapy offers patients
      improved therapy in the management of recurrent odontogenic keratocysts of the
      jaw, with lower recurrence and avoidance of ostectomy, which is likely to be
      accepted by the patients.

PMID- 16288326
TI  - [Construction of a dual-promoter DNA expression plasmid pCN-SSIE harboring gene
      encoding SBR of Streptococcus mutans and verification of its immunogenicity as
      DNA vaccine].
AB  - PURPOSE: To construct a dual-promoter expression plasmid that harbors the target
      gene encoding SBR of Streptococcus mutans and can be applied as DNA vaccine
      especially suitable for using attenuated Salmonella as delivery vector to elicit
      effective mucosal immune responses because of its advantage of possessing dual
      promoter. METHODS: Genes encoding SBR and green fluorescence protein gene (EGFP)
      were amplified by PCR and inserted to the proper sites of vector pCMVnir. Then
      IRES sequence was inserted between the genes coding for SBR and EGFP.
      Furthermore, a DNA fragment encoding tissue-type plasminogen activator (tPA)
      signal peptide was fused to the 5' end of target gene. Thereby, construction of
      the dual-promoter expression plasmid pCN-SSIE was completed and then the plasmid
      was analyzed with DNA sequencing and endonuclearase digestion mapping. The
      expressions of SBR protein by attenuated Salmonella SL3261 and CHO cell
      transformed or transfected by the plasmid were tested respectively. Finally,
      BALB/c mice were immunized through injecting intramuscularly with plasmid pCN
      SSIE and anti-SBR specific IgG in serum was tested. RESULTS: Both DNA sequencing
      and endonuclearase digestion mapping showed that the construction of pCN-SSIE was
      successful with its open reading frame being correct. The expressions of SBR
      protein in transformed attenuated Salmonella SL3261 and transfected CHO were
      detected, and anti-SBR specific IgG levels in serum of immunized mice were
      markedly higher than the control. CONCLUSION: The construction of the dual
      promoter expression plasmid pCN-SSIE was successful and the plasmid can express
      in prokaryocyte and eukaryocyte and elicit dramatic immune response when applied
      as DNA vaccine in experimental animal.

PMID- 16288328
TI  - [Effects of intra-arterial perfusion of cisplatin combined with concomitant
      radiation therapy on the healing of microvascular anastomoses: an experimental
      study in rabbits].
AB  - PURPOSE: To investigate the effects of intra-arterial perfusion of cisplatin and
      concomitant radiation therapy on the microvascular structure and the healing of
      anastomoses. METHODS: Three different treatments including intra-arterial
      perfusion of saline, intra-arterial perfusion of cisplatin, intra-arterial
      perfusion of saline and 25 Gy radiation therapy as well as intra-arterial
      perfusion of cisplatin and 25 Gy radiation therapy were conducted in 40 femoral
      arteries of 20 rabbits, which divided into 4 groups, control group, intra
      arterial chemotherapy group, radiation therapy group and combined treatment group
      accordingly. The bilateral femoral arteries were transected and anastomosed using
      microsurgical technique on 7th day after the treatments were completed. The
      effects of different treatments on the microvascular structure and the patency
      rates of anastomoses were investigated. RESULTS: The evidences of chronic damage
      to the vascular wall were observed in 4 groups. The changes in the combined
      treatment group were most serious. The damage to arterial wall in the radiation
      therapy group, chemotherapy group, and control group decrease gradually in order.
      Although the damages of the vascular wall were observed, there were no
      differences in the patency rates after microvascular anastomoses. CONCLUSION:
      These vessels can be used with caution as recipient vessels for free tissue
      transfer.

PMID- 16288327
TI  - [Preparation and property of recombinant human bone morphogenetic protein-2
      loaded hydrogel nanospheres and their biological effects on the proliferation and
      differentiation of bone mesenchymal stem cells].
AB  - PURPOSE: To prepare and study the recombinant human bone morphogenetic protein-2
      loaded dextran-based hydrogel nanospheres (rhBMP(2)-dex-NPs) sustained release
      system, and to evaluate its biological effects on cultured rabbit bone
      mesenchymal stem cells(BMSCs). METHODS: The rhBMP(2)-dex-NPs were prepared by
      improved emulsion polymerization method. Their morphology, size and size
      distribution, encapsulated ratio and stability were assessed by routine
      procedure. Dynamic dialysis method was used to determine the release
      characteristics of rhBMP(2)-dex-NPs in vitro. Cell culture technique and MTT
      colorimetric assay were used to evaluate the proliferation and differentiation of
      the BMSCs, ALP kit was used to evaluate the ALP activity of the BMSCs so as to
      show the differentiation of the cells by adding the rhBMP(2)-dex-NPs to the DMEM
      culture medium (B group) or rhBMP2 only (A group). Adding dex-NPs without rhBMP2
      (C group) and adding nothing (D group) were taken as the controls. The results
      were analyzed by statistical analysis software (SPSS10.0). RESULTS: The shape of
      rhBMP(2)-dex-NPs was spherical, with a size distribution of 20 nm. The
      encapsulated ratio was 83% and rhBMP(2)-dex-NPs could be kept more than 6 months
      under 4 degrees C without decomposition , destruction or deposition. The release
      profile in vitro was in accordance with two phases kinetics law, and more than
      80% of the encapsulated rhBMP(2) can be released during 12 days. Statistical
      analysis showed that rhBMP(2)-dex-NPs had biological activity, and could enhance
      both proliferation and differentiation of rabbit BMSCs significantly, the effect
      of the rhBMP(2)-dex-NPs was significantly higher than that of rhBMP(2) (P<0.01).
      During the first 3 days, the proliferation and differentiation of BMSCs between
      group A and B had no significance (P>0.05), but much faster than group C and D.
      After 5 to 7 days, rhBMP(2)-dex-NPs could enhance BMSCs proliferation and
      differentiation continually, but rhBMP2 had no enhancement any more. 7 days
      later, the difference between group A and B become much more significant
      (P<0.001). CONCLUSIONS: The rhBMP(2)-dex-NPs can release rhBMP2 more than 12 days
      and have long-drawn biological effects. To encapsulate rhBMP2 into dextran-based
      hydrogel nanospheres may be an effective way of growth factor controlled release
      in tissue engineering.

PMID- 16288329
TI  - [The mechanism of MAb225 regulating radiosensitivity of Tca8113 cell].
AB  - PURPOSE: The objective of this study was to investigate the mechanism of MAb225
      regulating radiosensitivity of Tca8113 cells. METHODS: Tca8113 cells were treated
      with MAb225 of different concentrations. The apoptosis rate was analysed by FCM
      and bi-fluorescence stain, the repair of DNA damage after radiation was analysed
      by single cell gel electrophoresis, cells redistribution in each phase of cell
      cycle was analysed by FCM, and GSH level of cell were assessed by
      spectrophotometer. RESULTS: Radiation alone (6 Gy) and MAb225 alone (0.5
      microg/ml) produced a 2-fold induction of apoptosis respectively, whereas
      exposure to MAb225 (0.5 microg/ml) combination with 6 Gy of radiation induced
      apoptosis 5-6 fold, compared to untreated controls (F test). The length of comet
      tail of cells which treated with MAb225 was significantly longer than that of the
      control cells (t test, P<0.05). The percentage of cells in S phase was
      significantly decreased in MAb225 treated cells. Intracellular GSH level of
      MAb225 treated cells was significantly lower than that of untreated cells (t
      test, P<0.05). CONCLUSION: MAb225 increased the radiosensitivity of Tca8113 cells
      by enhancing radiation-induced apoptosis, downregulating S phase percentage,
      inhibiting DNA repair after radiation and decreasing GSH level.

PMID- 16288330
TI  - [Changes of masticatory muscles after occlusal recovery in rats with unilateral
      chew].
AB  - PURPOSE: To study the effect of occlusal recovery on masticatory muscles in rats
      with unilateral chew. METHODS: 40 white rats were divided into two experimental
      groups and two control groups. The right upper and lower posterior teeth of all
      the rats were ground to the gingival level without occlusal contact. The rats of
      the first experimental and control group were killed 10 weeks late,those of the
      second groups were killed 16 weeks late. The pathological changes of masticatory
      muscles were studied. SPSS 10.0 software package was used for statistical
      analysis. RESULTS: There was significant correlation between the first
      experimental group and control group in the damage of masticatory muscles
      (Chi(2)=40, P<0.01). However,there was no significant correlation between the
      second experimental group and control group in the damage of masticatory muscles
      (Chi(2)=3.66, P>0.05). CONCLUSION: Early occlusal recovery can rehabilitate the
      damage of masticatory muscles in rats with unilateral chew.

PMID- 16288332
TI  - [The effect of sodium doecyl sulfate on Streptococcus sanguis biofilm].
AB  - PURPOSE: To investigate the effects of sodium doecyl sulfate on Streptococcus
      sanguis biofilm. METHODS: Streptococcus sanguis biofilm was formed on saliva
      coated glass(SCG) in a flow culture system, then exposed to different dental
      plaque control agents for 3,10,30 minutes including A: 300 mmol.L(-1) sodium
      doecyl sulfate (SDS); B: 2% chlorhexidine combined with 300 mmol.L(-1) SDS; C:
      0.3%triclosan combined with 300 mmol.L(-1) SDS. Confocal laser scanning
      microscopy and vital/dead fluorescent staining technique (vital stained green,
      dead stained red) were combined to observe biofilm thickness, bacterial density
      and viability, analysis of variance was used for comparison. RESULTS: The biofilm
      thickness and bacteria density reduced after treatment by 300 mmol.L(-1) SDS.
      However, there was no significant difference after treatment by 2% chlorhexidine
      combined with 300 mmol.L(-1)SDS; When treated by 0.3% triclosan combined with 300
      mmol.L(-1) SDS, most or all of the bacteria detached from the surface and
      dispersed. CONCLUSIONS: The combination of SDS (aimed at detachment) and
      triclosan (aimed at killing bacteria) may be most effective in controlling
      biofilm.

PMID- 16288331
TI  - [3-D FEA of the stress state of abutment and its periodontal tissue with three
      different retention styles in the absence of mandibular anterior teeth].
AB  - PURPOSE: To study the stress of the abutment and its periodontal tissue with
      different designs of retainer (type of retainer, place)in the same situation of
      dentural defect. METHODS: Based on the 3-D FEA database of RPD, the stress state
      of the abutment and its periodontal tissue was analyzed to choose the optimal
      retainer with the same situation of dentural defect. RESULTS: With three
      different retainer designs, the retainer on the second premolar and the first
      molar exerted the smallest stress on the abutment and its periodontal tissue,
      while the retainer on the first premolar and the first molar had the largest
      stress. CONCLUSION: Analysis for the health condition of abutment and its
      periodontal tissue is imperative for the selection of different designs of
      retainers.

PMID- 16288333
TI  - [Analysis of the influence of lower premolar rotation on TMJ stress distribution
      by finite element method].
AB  - PURPOSE: To evaluate the resultant differences of stress distribution in
      bilateral condyle when occlusal loads were changed with teeth rotation. METHODS:
      A three-dimensional FEA model containing human TMJ and left lower second premolar
      was developed using commercial FEA software ANSYS. Lower second premolar was
      applied with ICO occlusal loading in the load case 1. According to the same upper
      dentition in the load case 2, lower premolar was applied with occlusal loading
      when it was rotated 30 degree counter-clockwise in Frankfort horizontal plane
      level. In this two load cases,the different stress distributions of the condyle
      was investigated. RESULTS: The stress distribution of loading side condyle had
      changed abnormally when premolar rotation was performed. It had showed more
      disorderly than ICO loading in load case 1. In load case 1 the maximum main
      stress and Von Mises stress values increased from medial pole to lateral pole. In
      load case 2,the stress values mainly decreased from medial pole to lateral pole,
      but along the path there were some parts with values-increasing. The stress
      values of bilateral condyle in load case 2 were lower than that in load case 1,
      especially for the stress values of the opposite condyle. CONCLUSIONS: The stress
      distribution of loading side condyle got in disorder resulting from rotation of
      unilateral lower premolar.

PMID- 16288334
TI  - [Different histological changes of hard palates in rats with different areas of
      denudated bone].
AB  - PURPOSE: To explore the relationship between the histological changes of the
      denudated bone in the hard palate of rats and its sizes. METHODS: Sixteen three
      week-old SD male rats were randomly divided into 4 groups (a control group and 3
      experimental groups). In the three experimental groups, one and two and three
      quarters of the bilateral palatal mucoperiosteum were excised respectively. One
      animal in each group was sacrificed every two weeks and the histological
      differences were observed. RESULTS: Different histological changes were found
      among the groups. When the denuded part was over half of the palate, tight
      connections between scar tissues and both the palatal bone and the periodontal
      fibers were observed. Many necrotic bone tissues appeared in the mid-palate if
      more than three quarters of areas were exposed. CONCLUSION: Different sizes of
      denuded bone may lead to different histological appearances. Structures and
      tissues change more when denuded part of the bone is larger.

PMID- 16288335
TI  - [Experimental study of interstitial chemotherapy with PYM delivered from a solid
      implantable biodegradable polymer against human tongue SCC in tumor-bearing nude
      mice].
AB  - PURPOSE: This study was to evaluate the antitumor efficacy of implantable
      sustained Pingyangmycin (PYM) release system as a polymer based biocompatible
      implant administrated interstitially in tumors on tumor-bearing nude mice.
      METHODS: 20 tumor-bearing nude mice established with Tca8113 cell line were
      divided into five groups .Interstitial chemotherapy (polymer rod each containing
      0.1mg PYM was inserted into tumors through puncture needle with internal
      piston)was performed in mice of Group A, intravenous injection of PYM was made in
      mice of Group B, intratumoral injection of PYM was given in mice of Group C,
      polymer rod without PYM was inserted into tumors in Group D and normal saline was
      intravenously injected in mice of Group E as control. Same total dosage of PYM
      was given in Group A , B and C. Inhibition rate (IR) based on tumor measurement,
      apoptosis index (AI) of tumor cells based on TUNEL, apoptosis rate (AT) of tumor
      cells determined by flow cytometry and histopathological appearances were
      evaluated and analyzed in different groups. F test was used for statistical
      analysis by SAS 6.2 software package. RESULTS: The results showed that RI,AT and
      AI in experimental group (Group A) was significantly higher than that in other
      groups (P<0.05) Histopathologically, the proliferation of the tumor cells was
      relatively suppressed in Group A. CONCLUSIONS: Biodegradable PYM-polymer implant
      may be an optimistic form of drug delivery system in clinic and interstitial
      chemotherapy is especially suitable for tumors in oral-maxillofacial regions
      because of easy administration of the implant into the relatively superficial
      tumors in the regions.

PMID- 16288336
TI  - [The mechanic retention of the casting post with keeper in magnetic retentor
      overdenture].
AB  - PURPOSE: To reduce the cost of the fabrication of the magnetic retentor,and meet
      the clinical requirements, nonprecious alloy such as Co-Cr alloy was used to
      fabricate the magnetic retentor in overdenture , instead of the precious alloy.
      METHODS: A mandibular canine was chosen for root canal preparation in vitro.
      Thirty two resin posts were made in the same root canal with self-curing resin.
      The 32 resin posts were randomly divided into 4 groups. Among them,2 groups were
      fabricated with soft Co-Cr alloy, gold alloy(55.6%Au) respectively in vitro.
      Another 2 groups were fabricated with Co-Cr alloy, and the surface of the root
      casting post with keeper were treated with gold deposit and gold coating
      technique. After that, test of dislodgment force was done and one-way ANOVA was
      performed with SAS 6.2 software package. RESULTS: The dislodgment force of the
      root casting posts with keeper which were fabricated with the Co-Cr, Ni-Cr, and
      gold alloy had significant difference(P<0.01). While after surface treatment by
      gold deposit and gold coating technique on root casting posts with keeper that
      were fabricated with Co-Cr and Ni-Cr alloy, there was no significant difference
      in dislodgment force, compared with that of gold alloy. CONCLUSIONS: After
      surface treatment of the root casting posts with keeper which were fabricated
      with the Co-Cr and Ni-Cr alloy, the same clinical retentive effect can be
      obtained as the one that was fabricated with gold alloy.

PMID- 16288337
TI  - [The influence of botulinum toxin on the masticatory muscles of the
      temporomandibular joint osteoarthritis in rabbit].
AB  - PURPOSE: To study the influence of botulinum toxin on masticatory muscle activity
      in temporomandibular joint model osteoarthritis(TMJOA). METHODS: 30 adult rabbits
      were examined with EMG, and TMJOA was established by collagenase injection, then
      divided into experimental group and control group. EMG of masticatory muscles was
      recorded during postural position and clenching at the end of 4 weeks, 8 weeks
      and 12 weeks. Botulinum toxin was injected into the masseter muscle and temporal
      muscle in the experimental group. Those of the control group were only with
      TMJOA. All data were analyzed with group t test in SPSS 11.0. RESULTS: During
      postural position, EMG activity of masticatory muscles in the control group was
      significantly higher than that of the normal at each examination(P<0.05). EMG
      activity in th experimental group was lower than normal at the end of 4 weeks and
      8 weeks(P<0.05), but at the end of 12 weeks, the two groups showed no
      difference(P>0.05). During clenching, EMG activity in the control group was lower
      than normal at each measurement(P<0.05), EMG activity in the experimental group
      was lower than normal at the end of 4 weeks and 8 weeks(P<0.05), but showed no
      difference at the end of 12 weeks. CONCLUSION: Botulinum toxin can change and
      improve masticatory muscle function of TMJOA in rabbit.

PMID- 16288338
TI  - [Colonization relationship between Porphyromonas gingivalis and Bacteroides
      forsythus in the infected root canals with chronic apical periodontitis].
AB  - PURPOSE: To detect the distribution of P. gingivalis and B. forsythus in the
      infected root canals from Chinese chronic apical periodontitis, and investigate
      the colonization relationship between them in the root canals. METHODS: P.
      gingivalis and B. forsythus in the root canal samples of thirty-eight teeth with
      chronic apical periodontitis from 31 subjects who were referred to the Sichuan
      University West China Dental Hospital for dental treatment were studied with a
      16S rDNA-directed polymerase chain reaction method. Fisher's exact tset was used
      to detect B. forsythus in the infected root canals with or without P. gingivalis.
      OR was used to analyse the relationship between them. RESULTS: The prevalence in
      38 teeth was 39.5% for P. gingivalis, and 26.3% for B. forsythus, respectively.
      Significant positive relationship was shown in the combination of P. gingivalis
      and B. forsythus (OR=12, P<0.05). CONCLUSION: Both P. gingivalis and B. forsythus
      colonized in the root canals with chronic apical periodontitis and there was a
      positive relationship between P. gingivalis and B. forsythus in the infected root
      canal flora.

PMID- 16288339
TI  - [Research advances on genetics of nevoid basal cell carcinoma syndrome].
AB  - Nevoid basal cell carcinoma syndrome is an autosomal dominant genetic disease
      characterized by developmental abnormalities and tumorigenesis. Currently the
      mutation of PTCH gene is considered to be the molecular defect of this syndrome.
      This paper reviews the present status and progress on genetics about this
      syndrome.

PMID- 16288340
TI  - [Clinical application of maxillary sinus lifting, bone graft and simultaneous
      placement of implant].
AB  - PURPOSE: To evaluate the results of two kinds of sinus lifting techniques with
      simultaneous implant placement. METHODS: 31 maxillary sinus underwent two kinds
      of sinus lifting techniques and simultaneously 42 implants placement. The sinuses
      were observed 1, 3, 6 months after the surgery. RESULTS: There were no implants
      loose or lost; X ray examination showed well osseointegration and no maxillary
      sinusitis. All the patients finished implant prosthesis in 6 months
      postoperatively. Through 6-36 months' follow-up, clinical results were
      satisfactory. CONCLUSION: With properly handling of indication and the operation
      skill, the results of two kinds of maxillary sinus lifting techniques with bone
      grafting and simultaneously implants placement are both satisfactory.

PMID- 16288341
TI  - [Branchial cleft carcinoma from cleft cyst: report of one case].
AB  - Branchial cleft carcinoma is a rare malignancy, there still exist some
      controversies regarding to the differentiation of branchial cleft carcinomas.
      This article is aimed to familiarize clinicians with the presentation and
      treatment of the tumour and explores its origin. A 41-year old man who was seen
      with a large lesion of branchial cleft carcinoma with a slowly growing mass in
      the area of the left parotid gland was reported. The histological finding of
      dysplastic epithelium was next to direct invasive carcinoma. The diagnosis of a
      branchial cleft carcinoma requires the fulfillment of strict criteria. This case
      supports the origin of the carcinoma as being from an epithelial-lined cyst.

PMID- 16288342
TI  - [Clinical observation of CP and iodoform for intracanal medication].
AB  - To evaluate and compare the clinical effect of camphophenic (CP) and iodoform
      used as intracanal medication in root canal therapy for periapical periodontitis,
      305 teeth suffering from periapical periodontitis in 245 subjects were divided
      into two groups. The experimental group of 163 teeth was treated with CP and
      iodoform, while the control group of 142 teeth was treated with CP alone. The
      clinical effect after 10 days was observed. The result showed that the response
      rate in the teeth treated with CP and iodoform was 92.64%, significantly higher
      than that in the teeth treated with CP alone (79.58%), P<0.01.

PMID- 16288343
TI  - [Clinical observation of using composite resin to fill dental attrition on
      occlusal surface].
AB  - The purpose of this study was to evaluate the clinical effect of using composite
      resin to fill dental attrition on occlusal surface. Whether the dental attrition
      had enough space to the material was determined first. Sometimes grinding the
      sharp and steep cusps or ridges of the opposite teeth was needed. Then the dental
      attrition was cleaned thoroughly, and finally filled with CLEARFIL bond and
      composite resin without preparing cavity. The follow-up period was 1 year. Out of
      70 teeth from 25 patients, 52 were successful, 16 were curative, and 2 were
      failed. The curative rate was 97.14%. The method avoids endangering the dental
      pulp. It was easily accepted by the patients and operated by dentists, and can be
      widely applied in clinical cases.

PMID- 16288344
TI  - Spinal muscular atrophy--noninvasive ventilatory support in pediatrics.
AB  - The deterioration of the respiratory function in children suffering from
      degenerative neuromuscular disease is the main cause of the high mortality rate
      associated with these diseases. Noninvasive ventilation (NIV) has reduced the
      morbidity and mortality due to respiratory insufficiency in these children.
      However, the use of support ventilation in some cases of spinal muscular atrophy
      (SMA) is still controversial. A retrospective study of 22 patients suffering from
      SMA who were followed up in the Paediatric Hospital of Coimbra is presented: 7 of
      type I, 11 of type II, and 4 of type III. In 17 of these cases, non-invasive
      ventilation by mask was begun, and in 3 of them NIV was applied for prophylactic
      purposes. The 7 children with SMA type I began NIV when they were 13 months of
      age on average (3 months-3 years); 5 of them died, between 1 and 15 months after
      the beginning of the ventilation. Of the 11 children with SMA type II, 8 were
      submitted to NIV and one died 22 months later. Three of the children in this
      group began NIV in a prophylactic way, and in all of them a decrease in the
      thoracic deformity was observed. Of the 4 patients of type III, 2 of them were
      submitted to non-invasive ventilation. In all of the symptomatic cases, a
      decrease in the frequency and severity of respiratory infections was observed,
      after ventilation was started. The respiratory support with NIV may improve the
      quality of life of children suffering from SMA as well as prolong their life
      expectancies. In SMA type I, whose clinical manifestations are precocious and
      whose prognostic is very serious, the application of this support has been
      debated.

PMID- 16288345
TI  - The role of bronchoalveolar lavage in quantifying inhaled particles in silicosis.
AB  - Silicosis is a disease caused by inhalation and deposition of crystalline silica
      that produces a fibrous tissue reaction. Bronchoalveolar lavage is a noninvasive
      technique that allows identifying particles, thus characterizing exposure to
      mineral dust. The aim of this work was to study bronchoalveolar lavage as a mean
      of estimating the amount of alveolar particles in different forms of silicosis.
      Bronchoalveolar lavage was carried out in 27 silicotic patients with simple (n =
      12), complicated (n = 13), and acute (n = 2) forms of the disease and 7 healthy
      individuals as a control group. Macrophages were scored enumerating the
      percentage of cells with particles by polarizing light microscopy. Silicotic
      patients showed a marked increase in BAL cell particles compared to control
      population, however, relating simple to complicated silicosis, no significant
      difference was observed. In acute silicotic patients with massive silica dust
      exposure, more than 70% of BAL alveolar macrophages contained dust particles.
      When duration of exposure and retirement from work were evaluated, an inverse
      correlation between duration of exposure and the amount of alveolar dust, and a
      tendency to a smaller involvement on macrophages with the greater period of
      retirement from work were observed. These results suggest that particle analysis
      in BAL may be important in order to establish the nature and intensity of
      exposure.

PMID- 16288346
TI  - [Asbestos-related pleuropulmonary diseases: pictorial essay].
AB  - Pleural and pulmonary asbestos-related diseases range from benign conditions,
      like pleural effusion and pleural plaques, to some neoplasias, such as lung
      cancer and malignant mesothelioma. Pleural effusion is the earliest finding after
      asbestos exposure, but the imaging findings are not specific. Diffuse pleural
      thickening involves the visceral pleura and pleural plaques are considered to be
      hallmarks of exposure. Asbestosis is the pulmonary fibrosis due to asbestos.
      Rounded atelectasis is a peripheral lung collapse in these individuals, generally
      related to pleural disease. Some neoplasias, like lung carcinoma and pleural
      mesothelioma, are more prevalent in asbestos-exposed subjects. The aim of this
      essay is to illustrate the main imaging findings of asbestos-related diseases.

PMID- 16288347
TI  - [Asbestos-related pleural plaques: a literature review].
AB  - Pleural plaques (PP) are considered to be hallmarks of asbestos exposure. They
      constitute focal thickenings of the pleura and are commonly seen in patients
      without lung disease. They can involve parietal, diaphragmatic and mediastinal
      pleura. Chest x-ray is frequently used for PP diagnosis, but computed tomography,
      especially when used the high-resolution technique, is the imaging exam with the
      greatest sensibility and specificity. PP are almost always asymptomatic, but
      there are some controversial about their relationship with asbestos exposure
      indexes, pulmonary functional alterations and risk of neoplasias.

PMID- 16288348
TI  - [Kartagener syndrome].
AB  - A white, 48-year-old woman, natural from Uberaba-MG, presented herself to
      hospital. She had a picture of rest dyspnea, fever, productive cough, greenish
      catarrh and ventilatory-dependent thoracic pain, for 3 days. During
      investigation, through radiogram and thoracic tomography, it was visualized the
      presence of dextrocardia and consolidation in low right lobe by bronchopneumonic
      process. It was opted for hospitalization and antibiotic therapy. Investigation
      was carried on with tomography of mastoids and paranasal cavities which showed
      bilateral chronic otomastoiditis and images of chronic sinusopathy allowing the
      diagnosis of a case of Kartagener Syndrome. Our purpose in this case report is to
      include new informations for who search about this syndrome.

PMID- 16288349
TI  - [Infectious complications in pediatric cancer patients].
AB  - Infectious complications are still a major cause of morbidity and mortality in
      pediatric patients undergoing therapy for malignancy. Therapy-induced neutropenia
      is the most important risk factor for infectious risk in pediatric patients with
      cancer, but other factors, such as alterations in skin/mucosal barriers, and
      defects in cell-mediated or humoral immunity also contribute to the risk for
      infection. In most centers, about two thirds of bacteremic isolates are gram
      positive pathogens, whereas gram-negative organisms are isolated less frequently,
      but are associated with considerably higher mortality rates. Prolonged
      neutropenia increases the risk for invasive fungal infection. In most cases,
      fever is an important and early indication of serious infection, particularly in
      children with neutropenia. Discrimination between serious and inconsequential
      infection in febrile children with neutropenia at the time of presentation is
      difficult, and serum markers have not been proven to reliably indicate infection.
      Although several groups investigate risk categories based on clinical tests or
      the genetic background, the current paradigm is to treat all pediatric patients
      with neutropenia and fever with intravenous broad-spectrum antibiotics. It is
      hoped that the identification of one or more predictive factors may be useful for
      tailoring antibiotic prophylaxis and therapy in children with cancer.

PMID- 16288350
TI  - [Diagnostic procedures and management of Fever in pediatric cancer patients].
AB  - The rapid institution of empirical broad-spectrum antibiotics has become the gold
      standard of treatment for febrile neutropenic children undergoing therapy for
      cancer. With this approach, morbidity and mortality have dropped significantly
      but have not been eliminated altogether. In recent randomized studies evaluating
      different drug combinations, there is still a 3-10 % mortality reported in
      febrile, neutropenic cancer events. Despite improvements in invasive and non
      invasive diagnostic procedures, a majority of patients will receive antibiotic
      therapy despite an inability to identify a specific pathogen or source (fever of
      unknown origin, FUO). While there are evidence-based guidelines in adult patients
      with fever and neutropenia, data are less clear in the pediatric population.
      Experts agree on the early use of empirical antibiotic therapy, which covers
      Pseudomonas spp. and is initiated at the first sign of fever. The success of this
      approach has been based upon clinical intervention before the results of the
      diagnostic evaluation are available. In contrast, the use of aminoglycosides or
      glycopeptides is still a matter of debate, as it is the duration of antibiotic
      therapy. Based on published data in pediatric and adult patients with cancer, the
      current diagnostic procedures and therapeutic strategies will are discussed. The
      recommendations given are a consensus of the German Society of Pediatric Oncology
      and Hematology (GPOH) and the German Society of Pediatric Infectious Diseases
      (DGPI).

PMID- 16288351
TI  - [Bacterial infections in pediatric cancer patients].
AB  - Increased dose intensity and a better long term survival can not be reached in
      pediatric oncology without the judicious use of antibiotics. During periods with
      profound neutropenia and between intensive chemotherapy cycles are bacterial
      infections capable of disturbing the patients' quality of life; they may cause an
      acute life threatening situation and lead to a substantial increase in
      expenditures and consumption of ressources in supportive care. The non-judicious
      use of antibacterials may face the patient to an increased risk of adverse events
      and fosters the selection of resistant bacteria. This article provides the
      recommendations of the Infectious Diseases Working Party of the German Society
      for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric
      Hematology/Oncology (GPOH) for antibacterial therapy in pediatric oncology
      patients based upon the available literature and the clinical experience of the
      authors.

PMID- 16288352
TI  - [Diagnosis and management of fungal infections and pneumocystis pneumonitis in
      pediatric cancer patients].
AB  - Invasive fungal infections are important causes of morbidity and mortality in
      pediatric cancer patients with hematological malignancies and following
      allogeneic hematopoietic stem cell transplantation. This article provides the
      recommendations of the Infectious Diseases Working Party of the German Society
      for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric
      Hematology/Oncology (GPOH) for diagnosis and treatment of fungal infections
      including Pneumocystis jiroveci. They are based on specific pediatric
      pharmacological and regulatory considerations and on the results of clinical
      trials, case series and expert opinions using the evidence criteria set forth by
      the Infectious Diseases Society of America (IDSA). Recommendations for the most
      frequent clinical entities are summarized here. Options for initial therapy of
      uncomplicated candidemia include deoxycholate amphotericin B (DAMB), fluconazole
      (FLC), liposomal amphotericin B (LAMB), the combination of DAMB plus FLC as well
      as voriconazole (VCZ) for patients > 11 years. For acute disseminated
      candidiasis, the combination of DAMB plus flucytosine is recommended. Indwelling
      central venous catheters serve as infectious nidus and should be removed whenever
      feasible. First-line therapy for presumed or proven invasive Aspergillus
      infections in patients 12 years and older is VCZ with DAMB and LAMB serving as
      alternatives. Choices for patients < 12 years of age are essentially limited to
      DAMB and LAMB. Due to the yet lacking evidence for enhanced antifungal efficacy
      and the ongoing dosage finding of caspofungin (CAS) in pediatric patients,
      combination therapies (LAMB plus CAS or VCZ plus CAS) should only be considered
      for fulminant or massive, life threatening infections. In granulocytopenic
      patients, adjunctive therapy with colony-stimulating factors (G-CSF) is
      recommended. In patients under immunosuppressive therapy, glucocorticosteroids
      ought to be reduced or discontinued, if feasible. Surgical interventions are
      restricted to specific indications. Zygomyces infections are an indication for
      high-dose LAMB. The combination of DAMB plus flucytosine is the initial treatment
      of choice of cryptococcal mengoencephalitis, and for treatment of Pneumocystis
      jiroveci pneumonitis, trimethoprim/sulfamethoxazol or intravenous pentamidine is
      recommended. Beyond the listed entities, the article provides a brief review on
      the pharmacokinetics and dosing of antifungal agents in children and adolescents
      as well as detailed discussions and evidence-based recommendations for empirical
      antifungal therapy, diagnosis and treatment of superficial fungal infections, of
      invasive infections by previously rare fungal pathogens and endemic moulds and
      for adjunctive immunomodulatory and surgical interventions.

PMID- 16288353
TI  - [Viral infections in pediatric cancer patients].
AB  - Children with cancer or stem cell transplantation (SCT) are at considerable risk
      to develop life threatening viral infections. Due to both underlying disease and
      immunosuppressive therapy lymphocyte number and function are low and the cellular
      immunity against viral infections is restricted or missing. As immunosuppressive
      treatment regimens and mismatched or T-cell-depleted stem cell products are being
      used increasingly, viral infections will become an even greater problem in the
      future. PCR-based methods have become an indispensable tool for early
      recognition, preemptive therapy, and monitoring therapeutic responses by
      qualitative and quantitative approaches. Assays are now available that allow for
      parallel screening of the 16 most common viral agents. Responses to antiviral
      therapy are often limited in immunocompromised patients and mainly depend on the
      time of their initiation. Most antiviral agents have a toxicity profile that may
      become clinically relevant and curtail antiviral therapy. New options for
      treatment are therefore warranted. For the next future, these may include the
      transfer of specific T-cells and other immunotherapeutic approaches. This article
      provides the recommendations of the Infectious Diseases Working Party of the
      German Society for Pediatric Hematology/Oncology (GPOH) and the German Society
      for Pediatric Infectious Diseases (DGPI) for diagnosis and treatment of viral
      infections in children with cancer or post HSCT. They are based on the results of
      clinical trials, case series and expert opinions using the evidence criteria set
      forth by the Infectious Diseases Society of America (IDSA).

PMID- 16288354
TI  - [Parasitic diseases in pediatric cancer patients].
AB  - Parasitic infections are rare events in pediatric oncology. Transmission routes
      and diseases of most parasites do not differ significantly from those seen in
      otherwise healthy children. However, latent asymptomatic infections with
      Cryptosporidium spp., Leishmania spp., Strongyloides stercoralis and Toxoplasma
      gondii might exacerbate during immunosuppression. Screening in asymptomatic
      patients is often unsuccessful due to the low sensitivity of available assays
      except in toxoplasmosis. This article provides the recommendations of the
      Infectious Diseases Working Party of the German Society for Pediatric Infectious
      Diseases (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH)
      for the appropriate diagnostic procedures and antiparasitic treatment
      immunocompromised patients.

PMID- 16288355
TI  - [Diagnostics and management of central venous line infections in pediatric cancer
      patients].
AB  - Otherwise unexplained clinical signs of infection in patients with tunneled or
      totally implanted central venous access devices (CVAD) are highly suspicious of
      an underlying CVAD-associated infection. Diagnostic methods include catheter
      swabs, blood cultures and cultures of the catheter tip or port reservoir. In case
      of a suspected CVAD-related blood stream infection in pediatric cancer patients
      in situ treatment without prompt removal of the device can be tried. The removal
      of the CVAD should be considered, if bacteremia persists or relapses 72 hours or
      longer after the initiation of an (in vitro effective) antibacterial therapy
      administered through the line. The CVAD should be removed even earlier, if the
      patient suffers from hypotension or other signs of severe organ dysfunction
      related to the infection. If S. aureus, Pseudomonas aeruginosa, multiresistant
      Acinetobacter baumannii or Candida spp.are isolated from blood cultures taken
      through a CVAD, patients are at a high risk for severe complications and
      immediate device removal is also recommended. Duration of therapy depends on the
      immunological recovery of the patient (neutrophils counts), the pathogen isolated
      and on the presence of related complications like thrombosis, pneumonia,
      endocarditis, osteomyelitis. Antibiotic-lock techniques in addition to systemic
      treatment are beneficial in Gram-positive infections. Although prospectively
      controlled studies are missing, the concomitant use of urokinase- or taurolidine
      seems to favour catheter salvage.

PMID- 16288356
TI  - [Intraabdominal and hepatic infections in pediatric cancer patients].
AB  - Common complications involved in treating pediatric patients with cancer are
      bacterial, viral and fungal infections of the gastrointestinal tract including
      esophagitis, gastritis, duodenitis, colitis and hepatobiliar infections. In many
      cases there are multiple factors that predispose these patients to
      gastrointestinal infections, such as granulocytopenia, T-cell dysfunction, and
      mucosal damage. In addition, newer therapies have changed the spectrum of
      infection that is seen in these patients. The profound T-cell suppression
      associated with therapies such as stem cell transplantation has led to the
      emergence of previously rare infections including cytomegalovirus and adenovirus.
      This article provides the recommendations of the Infectious Diseases Working
      Party of the German Society for Pediatric Infectious Diseases (DGPI) and the
      German Society for Pediatric Hematology/Oncology (GPOH) for diagnosis,
      prevention, and management of local as well as invasive infections of the
      gastrointestinal tract.

PMID- 16288357
TI  - [Dermatologic manifestations of infections in pediatric cancer patients].
AB  - Cutaneous infections in children and adolescents with cancer are frequently
      associated with a marked morbidity and mortality. Particularly neutropenic
      patients undergoing intensive cytostatic therapy or after allogenic stem cell
      transplantation are affected. In this group of patients, atypical manifestations
      of infectious skin disease are frequently observed which represent a diagnostic
      challenge. It is therefore essential for clinicians to be familiar with the
      clinical presentation, diagnostic methods and management of skin infections
      encountered in pediatric oncology.

PMID- 16288358
TI  - [Diagnosis and management of central nervous system infections in pediatric
      cancer patients].
AB  - Infections of the central nervous system (CNS) are a common cause of neurological
      abnormalities in pediatric oncology patients apart from cancer disease of the
      CNS. Often symptoms do not present unequivocally, impeding a clear distinction
      from other differential diagnosis. Repeated neurological examinations of the
      patient allow selecting the necessary laboratory tests and imaging techniques. As
      delayed antiinfectious treatment is associated with high mortality and severe
      sequelae of survivors, patients do need empirical therapy using adequate doses
      until diagnostic results allow a more specific treatment. This article provides
      the recommendations of the Infectious Diseases Working Party of the German
      Society for Pediatric Infectious Diseases (DGPI) and the German Society for
      Pediatric Hematology/Oncology (GPOH) for diagnosis and treatment of infections of
      the CNS in immunocompromised patients.

PMID- 16288359
TI  - [Management of septic shock and acquired respiratory distress syndrome in
      pediatric cancer patients].
AB  - Septic shock occurs in 6 % of paediatric cancer patients with neutropenia and
      fever. The mortality of the septic shock is 40 % in BMT patients and 5 % in
      others. One third of paediatric ARDS cases affect immunocompromised individuals
      with a total mortality of 45 % and 80 % after BMT. Septic shock is caused by gram
      negative bacteria in more than 75 %. ARDS is due to pneumonia in more than 50 %,
      sepsis in about 25 %. This article provides the recommendations of the Infectious
      Diseases Working Party of the German Society for Pediatric Infectious Diseases
      (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH) for
      treatment of septic shock and ARDS. Therapy of septic shock includes early
      antibiotic therapy and volume expansion (> or = 40 ml/kg initially). Refractory
      shock requires vasopressors (noradrenaline), followed by a judicious circulatory
      management. Hydrocortisone is indicated in patients with high probability of
      adrenal insufficiency. Mainstay of ARDS therapy is ventilation with sufficient
      end-expiratory pressure (PEEP) to prevent loss of functional residual capacity
      and with limited tidal volumes (< or = 6 ml/kg) and limited inspiratory pressure
      (< 35 cm H(2)O) respectively, to minimize ventilator induced lung injury. Volume
      therapy consists of maintenance of sufficient preload to counteract the impaired
      venous return, induced by positive pressure ventilation. Diuretics and eventually
      veno-venous haemofiltration are used to reduce free lung water. Surfactant
      application may be considered in severe cases. Steroids are indicated in
      pneumocystis carinii pneumonia and in engraftment pneumonitis.

PMID- 16288360
TI  - [Infectious complications in the child undergoing hematopoietic stem cell
      transplantation].
AB  - Infectious complications are a major cause of morbidity and mortality in
      pediatric and adult patients undergoing hematopoietic stem cell transplantation.
      The incidence and the severity code of infections depend on the function of the
      host's immune system. This function is strongly correlated to the application of
      immune suppressive therapy and the speed of immune reconstitution after stem cell
      transplantation (SCT). The immune reconstitution can be divided into an early,
      intermediate and a late phase. This article describes the risk of infections
      during the different phases of immune reconstitution after stem cell
      transplantation in children. The basic differences between conventional treated
      oncologic, autologous and allogenic transplanted children will be presented.
      Beside the risk in the phase of aplasia there should be pointed out that long
      term immune deficiency is a strong factor for developing a severe infection after
      SCT.

PMID- 16288361
TI  - [Antimicrobial agents in pediatric cancer patients with hepatic or renal
      impairment].
AB  - Antimicrobial agents are among the most frequently prescribed therapeutics in the
      supportive care of children and adolescents with cancer or following
      hematopoietic stem cell transplantation. Most of these agents are cleared from
      the body by elimination of unchanged drug by the kidney and/or metabolism by the
      liver. Impaired renal and hepatic function may have profound effects on the
      pharmacokinetics and pharmacodynamics of antimicrobial agents, necessitating
      modification of the dosage regimen in order to avoid toxicity through
      accumulation of the parent and/or its metabolites. Key to minimize such
      toxicities is a thorough understanding of the antimicrobial drug armamentarium
      and a careful evaluation of benefits and risks of antimicrobial interventions.
      This article reviews the mechanisms of renal and hepatic drug clearance in the
      normal state and in the state of functional impairment, their implications for
      antimicrobial therapy and dosage recommendations for pediatric cancer patients
      with impaired renal or hepatic function.

PMID- 16288362
TI  - [Drug interactions of antimicrobial agents in children with cancer].
AB  - Antimicrobial agents are among the most common therapeutics prescribed to
      children and adolescents with hematologic/oncologic disorders. Because of the
      polymorbid state of most patients, they are frequently administered concomitantly
      with other drugs, resulting in a considerable potential for drug interactions.
      While many of these interactions are of marginal clinical significance, others
      are associated with substantial risks of decreased therapeutic efficacy or
      increased drug toxicity. Prevention and recognition of drug interactions are
      therefore of vital importance to optimizing effective use of antimicrobials and
      enhancing patient outcome. Key to minimize drug interactions are a thorough
      understanding of the pharmacology of frequently used antimicrobial agents and a
      careful evaluation of risks and benefits of potentially interacting drugs. This
      article reviews mechanisms and clinical relevance of drug interactions of
      antimicrobial agents in the supportive care of children and adolescents with
      hematologic/oncologic disorders and provides strategies for their prevention.

PMID- 16288363
TI  - When can we stop using oral poliovirus vaccine?

PMID- 16288364
TI  - Trichomoniasis in adolescents: a marker for the lack of a public health response
      to the epidemic of sexually transmitted diseases in the United States.

PMID- 16288365
TI  - Prevalence, incidence, natural history, and response to treatment of Trichomonas
      vaginalis infection among adolescent women.
AB  - BACKGROUND: Trichomonas vaginalis infection is a sexually transmitted infection
      (STI) linked with reproductive health complications. However, few data exist
      concerning the epidemiologic profile of this pathogen in adolescent women, a
      group at high risk for other STIs. METHODS: Our objective was to describe the
      prevalence, incidence, natural history, and response to treatment of T. vaginalis
      infection in adolescent women. Women 14-17 years old were followed for up to 27
      months. Vaginal swab samples were obtained during quarterly clinic visits and
      were self-obtained weekly during 12-week diary collection periods. The weekly
      samples were tested quarterly. Infections were identified by polymerase chain
      reaction and were treated with 2.0 g of oral metronidazole. Analysis was
      performed on the subset of participants who returned for at least 1 quarterly
      clinic visit. RESULTS: T. vaginalis infection was identified in 6.0% (16/268) of
      the participants at enrollment. Overall, 23.2% (57/245) of the participants with
      at least 3 months of follow-up had at least 1 infection episode; 31.6% (18/57)
      experienced multiple episodes. Seventy-two incident infection episodes were
      diagnosed. When treatment was not documented, weekly samples from participants
      were positive for up to 12 consecutive weeks. After treatment, T. vaginalis DNA
      was undetectable within 2 weeks in all but 3 participants. CONCLUSIONS: The
      incidence of T. vaginalis infection is high among adolescent women; untreated
      infections may last undetected for 3 months or longer. Reinfection is common.
      Treatment with oral metronidazole is effective, and T. vaginalis DNA disappears
      rapidly after treatment.

PMID- 16288367
TI  - Mycobacterium tuberculosis-induced cytokine and chemokine expression by human
      microglia and astrocytes: effects of dexamethasone.
AB  - Although corticosteroids are recommended as adjunctive therapy for tuberculous
      meningitis, the mechanism underlying their beneficial effect is poorly
      understood. In this study, human microglia and astrocytes were infected with
      Mycobacterium tuberculosis H37Rv, and cytokine and chemokine expression was
      examined with and without dexamethasone treatment. Microglia were the principal
      cells infected by tubercle bacilli, which elicited robust amounts of several
      cytokines and chemokines. Treatment with dexamethasone markedly suppressed
      production of these mediators. The results of this study support the concept that
      microglia play an important role in neuropathogenesis of tuberculosis and that
      dexamethasone could operate via modulation of the production of proinflammatory
      cytokines and chemokines by these brain macrophages.

PMID- 16288366
TI  - Effective treatment of erythema nodosum leprosum with thalidomide is associated
      with immune stimulation.
AB  - The immunomodulatory drug thalidomide is the treatment of choice for erythema
      nodosum leprosum (ENL), an inflammatory cutaneous and systemic complication of
      multibacillary leprosy. To elucidate the mechanism of action of thalidomide in
      this syndrome, we prospectively investigated 20 patients with ENL who were
      treated with thalidomide for 21 days. All patients responded to treatment, with
      the majority of them having complete resolution of cutaneous lesions within 7
      days. This response was associated with a marked but transient increase in ex
      vivo mitogen-induced expression of interleukin (IL)-2 and interferon- gamma by
      CD4(+) and CD8(+) T cells that was observed on treatment day 7, but these
      returned to pretreatment levels by day 21. Plasma tumor necrosis factor- alpha
      levels were not high at baseline, and they increased modestly during treatment.
      Plasma levels of IL-12 increased steadily during thalidomide treatment. Hence,
      the therapeutic effect of thalidomide in ENL appears to be associated with
      transient immune stimulation, which suggests that the drug may promote an active
      immunoregulatory response.

PMID- 16288368
TI  - Association between the infectivity of Mycobacterium tuberculosis strains and
      their efficiency for extrarespiratory infection.
AB  - Extrarespiratory tuberculosis is determined mainly by impaired immunity of the
      host. The additional role played by bacterial factors in determining whether an
      infection by Mycobacterium tuberculosis disseminates to extrarespiratory sites
      has not been analyzed in depth. In the present study, we selected patients who
      were dually infected with 2 M. tuberculosis strains but in whom only one of the
      strains infected extrarespiratory sites, whereas the other strain remained at the
      respiratory site. We compared the infectivity of respiratory and extrarespiratory
      strains in a newly designed ex vivo competitive macrophage coinfection assay and
      in the murine aerosol-infection model. The extrarespiratory strains infected
      macrophages more efficiently than did the respiratory strains, and a
      representative extrarespiratory strain also showed higher infectivity in vivo.
      Our data indicate that, in addition to host immune status, a bacterial factor-
      the infectivity of a M. tuberculosis strain--should be considered in determining
      the likelihood of extrarespiratory dissemination.

PMID- 16288369
TI  - It's not the heat, it's the humidity: wet weather increases legionellosis risk in
      the greater Philadelphia metropolitan area.
AB  - BACKGROUND: Legionella species are abundant in the environment and are
      increasingly recognized as a cause of severe pneumonia. Increases in cases of
      community-acquired legionellosis in the greater Philadelphia metropolitan area
      (GPMA) led to concern that changing environmental factors could influence
      occurrence of disease. METHODS: We evaluated the association between weather
      patterns and occurrence of legionellosis in the GPMA, using both traditional
      Poisson regression analysis and a case-crossover study approach. The latter
      approach controls for seasonal factors that could confound the relationship
      between weather and occurrence of disease and permits the identification of acute
      weather patterns associated with disease. RESULTS: A total of 240 cases of
      legionellosis were reported between 1995 and 2003. Cases occurred with striking
      summertime seasonality. Occurrence of cases was associated with monthly average
      temperature (incidence rate ratio [IRR] per degree Celsius, 1.07 [95% confidence
      interval [CI], 1.05-1.09]) and relative humidity (IRR per 1% increase in relative
      humidity, 1.09 [95% CI, 1.06-1.12]) by Poisson regression analysis. However, case
      crossover analysis identified an acute association with precipitation (odds ratio
      [OR], 2.48 [95% CI, 1.30-3.12]) and increased humidity (OR per 1% increase in
      relative humidity, 1.08 [95% CI, 1.05-1.11]) 6-10 days before occurrence of
      cases. A significant dose-response relationship for occurrence of cases was seen
      with both precipitation and increased humidity. CONCLUSIONS: Although, in the
      GPMA, legionellosis occurred predominantly during summertime, the acute
      occurrence of disease is best predicted by wet, humid weather. This finding is
      consistent with the current understanding of the ecological profile of this
      pathogen and supports the contention that sporadic legionellosis occurs through
      contamination of water sources.

PMID- 16288370
TI  - Active immunization with a detoxified endotoxin vaccine protects against lethal
      polymicrobial sepsis: its use with CpG adjuvant and potential mechanisms.
AB  - BACKGROUND: An experimental vaccine for sepsis, composed of detoxified
      Escherichia coli J5 lipopolysaccharide (LPS) complexed with the outer membrane
      protein (OMP) of Neisseria meningitidis group B, induces anti-core glycolipid
      antibody and has been tested in pilot studies in human volunteers. METHODS: Mice
      were immunized with the LPS-J5/OMP vaccine with or without synthetic
      oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs as a vaccine
      adjuvant (CpG ODN). The efficacy of the vaccine-induced antibody response was
      tested in a cecal ligation and puncture model. RESULTS: Immunization resulted in
      a >20-fold increase in anti-core glycolipid antibody levels, which were further
      increased 5-fold by the addition of CpG ODN, compared with the levels in mice in
      the control group. The vaccine provided a survival advantage after a cecal
      ligation and puncture was performed (P < .01) and significantly decreased the
      levels of bacteria in organs. Immunoglobulin G (IgG) anti-core glycolipid
      antibodies were decreased in mice to a significantly greater extent than were
      levels of total circulating IgG or IgG to the OMP part of the vaccine complex,
      suggesting specific epitope binding and clearance. CONCLUSIONS: These results
      indicate that the detoxified LPS-J5/OMP vaccine induces high levels of antibody
      against the core glycolipid of LPS and functions in vivo to promote clearance of
      gram-negative bacteria and improve the outcome of experimental polymicrobial
      intra-abdominal sepsis.

PMID- 16288371
TI  - Protective immunity against Streptococcus pyogenes challenge in mice after
      immunization with fibronectin-binding protein.
AB  - BACKGROUND: Surface-associated fibronectin (Fn)-binding proteins of Streptococcus
      pyogenes play an important role in the bacterial invasion of epithelial cells. We
      examined the functional domain and protective antigenicity of the Fn-binding
      protein FbaA. METHODS: To investigate the functional domain of FbaA and its
      localization on S. pyogenes, a series of recombinant glutathione S-transferase
      (GST)-truncated FbaA proteins was used for immunofluorescent microscopy, ligand
      blotting, and Biacore analyses. Mice were immunized with the truncated proteins
      for the determination of the immunogenic domains that contribute to protection
      against S. pyogenes infection. RESULTS: Ligand-blotting and Biacore analyses
      revealed that the FbaA fragments harboring a proline-rich repeat domain (RD), but
      not the N- and C-terminal regions, possessed Fn-binding activity.
      Immunofluorescent microscopy findings showed that the N terminus and RD were
      exposed to external regions, which suggests that the RD serves as a Fn-binding
      element on live organisms. Specific antibodies were efficiently induced in N
      terminus- and RD-immunized mice and demonstrated bactericidal activity against S.
      pyogenes in vitro. FbaA-immunized mice survived significantly longer than GST
      immunized mice after infection with serotype M1 and M49 strains expressing FbaA.
      CONCLUSION: The Fn-binding RD and N terminus of FbaA are potential vaccine
      candidates for M1 strains of S. pyogenes infection.

PMID- 16288372
TI  - Effect of different vaccination schedules on excretion of oral poliovirus vaccine
      strains.
AB  - Inactivated poliovirus vaccine (IPV) is believed to induce significantly lower
      mucosal immunity than oral poliovirus vaccine (OPV). Most of the data supporting
      this were generated before enhanced IPV (eIPV) was introduced. Excretion of
      poliovirus by OPV recipients can be used to assess intestinal immunity. We
      studied polymerase chain reaction amplification of viral complementary DNA from
      the stool of children vaccinated with either OPV alone or eIPV. Of first-time OPV
      recipients, 92% excreted virus after 1 week, and 81% excreted virus after 3
      weeks. Prior vaccination with OPV reduced the number to 22% and shortened the
      duration of virus excretion (to 5% after 3 weeks). Two doses of IPV reduced the
      number of poliovirus-positive 1-week samples (to 76%), the duration of shedding
      (to 37% at 3 weeks), and the quantity of excreted virus. This suggests that IPV
      vaccinated communities are partially protected from the spread of poliovirus.
      Further enhancement of IPV potency may lead to even higher levels of mucosal
      immunity.

PMID- 16288373
TI  - Randomized controlled trial of an adjuvanted human papillomavirus (HPV) type 6
      L2E7 vaccine: infection of external anogenital warts with multiple HPV types and
      failure of therapeutic vaccination.
AB  - BACKGROUND: Cellular immunity is involved in spontaneous clearance of anogenital
      warts caused, most typically, by human papillomavirus (HPV) type 6 or 11,
      supporting the concept of therapeutic vaccination. A therapeutic vaccine composed
      of HPV-6 L2E7 fusion protein and AS02A adjuvant was evaluated in conjunction with
      conventional therapies in subjects with anogenital warts. METHODS: A total of 457
      subjects with anogenital warts were screened, of which 320 with HPV-6 and/or HPV
      11 infection were enrolled into 2 double-blind, placebo-controlled substudies.
      Three doses of vaccine or placebo were administered along with either ablative
      therapy or podophyllotoxin. RESULTS: Although a positive trend toward clearance
      was seen in patients infected with only HPV-6, in neither substudy did the
      vaccine significantly increase the efficacy of conventional therapies, despite
      induction of adequate immune responses. Extensive HPV typing by polymerase chain
      reaction demonstrated that a majority of screened subjects (73.7%) were infected
      with HPV-6 and/or HPV-11 and that a large proportion (40.1%) were infected with
      multiple HPV types. HPV types that put subjects at high risk of development of
      cervical cancer were detected in 39.8% of subjects. CONCLUSIONS: Infection with
      multiple HPV types, including high-risk types, is common in anogenital wart
      disease. Therapeutic vaccination failed to increase the efficacy of conventional
      therapies.

PMID- 16288374
TI  - A prospective follow-up of Epstein-Barr virus LMP1 genotypes in saliva and blood
      during infectious mononucleosis.
AB  - To monitor multiple Epstein-Barr virus (EBV) infections during the early and
      convalescent stages of infectious mononucleosis (IM), a cloning and sequencing
      study of the LMP1 gene was conducted in saliva and peripheral blood mononuclear
      cells (PBMCs) from 23 patients with IM at day 0 (D0) and day 180 (D180) after the
      onset of the disease. Multiple EBV strains were detected in 9 (39%) of the
      patients during follow-up, with 7 of 9 cases detected as early as D0. Six of the
      nine patients harbored the same dominant strain in saliva and PBMCs during follow
      up, with a trend toward a restriction of the number of EBV strains in saliva but
      not in PBMCs at D180. Furthermore, transmission of a minor strain was observed
      between partners in a heterosexual couple. There was no correlation between
      multiple infections and EBV DNA load in either compartment.

PMID- 16288375
TI  - In vivo clearance of hepatitis C virus nonstructural 3/4A-expressing hepatocytes
      by DNA vaccine-primed cytotoxic T lymphocytes.
AB  - A key question in the development of a therapeutic vaccine against hepatitis C
      virus (HCV) is whether vaccine-primed T cells enter the liver and eliminate HCV
      expressing hepatocytes. In the absence of an infectious small-animal model, we
      evaluated liver homing of vaccine-primed T cells in mice with transient hepatic
      transgene expression of the HCV nonstructural 3/4A (NS3/4A) protein. We found
      that T cells primed by transdermal DNA-based vaccination entered the liver and
      cleared NS3/4A-expressing hepatocytes in transiently transgenic CD8(+/+) mice but
      not in CD8(-/-) mice. Hence, peripherally primed NS3/4A-specific CD8(+) T cells
      home to the liver and clear HCV protein-expressing hepatocytes.

PMID- 16288376
TI  - Impact of immunization with glycoprotein D2/AS04 on herpes simplex virus type 2
      shedding into the genital tract in guinea pigs that become infected.
AB  - In recent clinical trials, a vaccine that contained herpes simplex virus type 2
      (HSV-2) glycoprotein D (gD2) and the adjuvant AS04 afforded HSV-seronegative
      women significant protection against HSV-2 genital disease and limited protection
      against infection. Similarly, in guinea pigs, immunization with the vaccine
      provided significant protection against genital HSV-2 disease but did not prevent
      mucosal infection. We explored the impact of immunization on the magnitude of
      latent virus infection and on the frequency and magnitude of virus reactivation
      as measured by both recurrent disease and viral shedding into the genital tract.
      Guinea pigs immunized with gD2/AS04 were shown by quantitative polymerase chain
      reaction (qPCR) analysis to have significantly less latent viral DNA in the
      ganglia than did naive control guinea pigs and to have a reduced incidence and
      frequency of recurrent disease. By contrast, all immunized guinea pigs shed virus
      into the genital tract with a frequency comparable to that seen in control guinea
      pigs. However, the amount of virus shed was significantly reduced, as measured by
      qPCR. These data suggest that immunization could affect transmission by altering
      viral shedding patterns.

PMID- 16288377
TI  - Poliovirus vaccine shedding among persons with HIV in Abidjan, Cote d'Ivoire.
AB  - BACKGROUND: As polio eradication nears, the development of immunization policies
      for an era without the disease has become increasingly important. Outbreaks due
      to circulating vaccine-derived poliovirus (VDPV) and rare cases of
      immunodeficient persons with prolonged VDPV shedding lend to the growing
      consensus that oral poliovirus vaccine (OPV) use should be discontinued as soon
      after polio eradication as possible. The present study was conducted to assess
      whether persons infected with human immunodeficiency virus (HIV) experience
      prolonged VDPV shedding and serve as a source of reintroduction of virus into the
      population. METHODS: Adults infected with HIV had specimens tested (1) 8 months
      after a mass OPV campaign, to determine whether poliovirus related to OPV
      administered during the campaign was present (i.e., prolonged excretion), and (2)
      starting 7 weeks after a subsequent campaign, to determine whether poliovirus
      could be detected after the height of OPV exposure. RESULTS: A total of 419
      participants were enrolled--315 during the 8-12 months after an OPV campaign held
      in 2001 and 104 during the 7-13 weeks after a 2002 campaign. No poliovirus was
      isolated from any participants. CONCLUSIONS: It appears unlikely that adults
      infected with HIV experience prolonged vaccine virus shedding, and, therefore,
      they probably represent a minimal risk of reintroducing vaccine virus into the
      population after poliovirus has been eradicated.

PMID- 16288378
TI  - Safety and immunogenicity of an HIV-1 recombinant canarypox vaccine in newborns
      and infants of HIV-1-infected women.
AB  - Pediatric AIDS Clinical Trials Group protocol 326 is a study of 2 formulations of
      recombinant canarypox ALVAC vaccine (vCP205) against human immunodeficiency virus
      type 1 (HIV-1). HIV-1-exposed infants were randomized to receive 1 of 2
      formulations of vCP205 or placebo at birth and 4, 8, and 12 weeks. The vaccines
      were safe. Lymphoproliferative responses were detected at > or =2 time points in
      44%-56% of vaccinees and none of the placebo recipients. A cytotoxic T lymphocyte
      response on at least 1 occasion was detected in 62.5% of infants in cohort 1
      (10(6.08) median tissue culture dose [TCID(50)] vaccine formulation) and 44% of
      infants in cohort 2 (10(6.33) TCID(50) vaccine formulation). Rare mucosal
      immunoglobulin A responses and no measurable vaccine-elicited serum antibodies
      were detected. In children, vCP205 appeared to be safe and immunogenic.

PMID- 16288379
TI  - The influence of HIV infection on clinical presentation, response to treatment,
      and outcome in adults with Tuberculous meningitis.
AB  - BACKGROUND: Tuberculous meningitis occurs more commonly in human immunodeficiency
      virus (HIV)-infected individuals than in HIV-uninfected individuals, but whether
      HIV infection alters the presentation and outcome of tuberculous meningitis is
      unknown. METHODS: We performed a prospective comparison of the presenting
      clinical features and response to treatment in 528 adults treated consecutively
      for tuberculous meningitis (96 were infected with HIV and 432 were uninfected
      with HIV) in 2 tertiary-care referral hospitals in Ho Chi Minh City, Vietnam.
      Logistic regression was used to model variables associated independently with HIV
      infection, 9-month survival, and the likelihood of having a relapse or an adverse
      drug event. Kaplan-Meier estimates were used to compare survival rates and times
      to fever clearance, coma clearance, relapse, and adverse events. RESULTS: HIV
      infection did not alter the neurological presentation of tuberculous meningitis,
      although additional extrapulmonary tuberculosis was more likely to occur in HIV
      infected patients. The 9-month survival rate was significantly decreased in HIV
      infected patients (relative risk of death from any cause, 2.91 [95% confidence
      interval, 2.14-3.96]; P < .001), although the times to fever clearance and coma
      clearance and the number or timing of relapses or adverse drug events were not
      significantly different between the groups. CONCLUSIONS: HIV infection does not
      alter the neurological features of tuberculous meningitis but significantly
      reduces the survival rate.

PMID- 16288380
TI  - CD4+ T cell recovery beyond the first year of complete suppression of viral
      replication during highly active antiretroviral therapy is not influenced by CD8+
      T cell activation.
AB  - CD38 expression on CD8(+) T cells was longitudinally assessed in 31 human
      immunodeficiency virus (HIV)-infected persons with undetectable plasma viremia
      who had undergone highly active antiretroviral therapy (HAART) for 12 months and
      were followed for a mean of 30 months thereafter. Overall, CD4(+)T cell counts
      increased during follow-up, whereas CD38 expression remained stable. However, a
      subset of patients showed declines in CD38 expression, and, conversely, another
      subset showed increases in CD38 expression. No association could be found between
      long-term gains in CD4(+) T cells and evolution of CD38 expression. Thus,
      activation of CD8(+) T cells does not seem to be associated with the extent of
      CD4(+) T cell recovery beyond the first year of successful HAART.

PMID- 16288381
TI  - South African GB virus C isolates: interactions between genotypes 1 and 5
      isolates and HIV.
AB  - GB virus C (GBV-C) is a common, apparently nonpathogenic human flavivirus that
      has been associated in some studies with prolonged survival in human
      immunodeficiency virus (HIV)-positive persons. There are 5 distinct GBV-C
      genotypes localized to specific geographic regions, and genotype 2 has been
      previously shown to inhibit HIV replication in vitro in lymphocyte cultures. We
      identified GBV-C virus isolates representing genotypes 1, 2, and 5 in samples
      from South African blood donors. GBV-C genotype 1 and 5 isolates replicated in
      lymphocyte culture, inhibited X4 and R5 HIV-1 isolates, and induced RANTES and
      stromal-derived factor-1 chemokines in vitro. Thus, African GBV-C genotypes can
      inhibit HIV replication in vitro.

PMID- 16288382
TI  - Urinary disease in 2 Dogon populations with different exposure to Schistosoma
      haematobium infection: progression of bladder and kidney diseases in children and
      adults.
AB  - BACKGROUND: Schistosoma haematobium infection causes severe urinary disease and
      considerable mortality. The factors that determine disease progression from mild
      to severe stages are not fully understood. METHODS: Here we describe a cross
      sectional epidemiological study of kidney and bladder diseases in 2 Dogon
      populations with different exposure to S. haematobium infection. RESULTS: Early
      and high exposure resulted in more-severe disease, especially among young
      subjects, without clear evidence of a more-rapid development of immunity.
      Nevertheless, 50%-60% of subjects of all age classes in both villages showed no
      evidence of disease. Kidney and bladder disease peaked biphasically among young
      subjects and adults >25 years old. The first peak corresponded with infections of
      maximum intensity, whereas the second peak occurred among adults with infections
      of very low intensity. Kidney disease was correlated with circulating anodic
      antigen concentration in serum, whereas bladder disease was correlated with egg
      count and eosinophil cationic protein concentration in urine. Kidney and bladder
      disease did not correlate. Severe kidney disease was more frequent in certain
      families. CONCLUSIONS: The frequency of urinary disease is increased by
      infections acquired early during life, is regulated by strong clinical immunity
      in certain subjects, and may be dependent on hereditary factors. Kidney and
      bladder disease may involve different mechanisms of pathogenesis, which may
      differ between children and adults.

PMID- 16288383
TI  - Functional significance of low-intensity polyparasite helminth infections in
      anemia.
AB  - BACKGROUND: We wanted to quantify the impact that polyparasite infections,
      including multiple concurrent low-intensity infections, have on anemia. METHODS:
      Three stool samples were collected and read in duplicate by the Kato-Katz method
      in a cross-sectional sample of 507 children from Leyte, The Philippines. The
      number of eggs per gram of stool was used to define 3 infection intensity
      categories--uninfected, low, and moderate/high (M+)--for 3 geohelminth species
      and Schistosomiasis japonicum. Four polyparasite infection profiles were defined
      in addition to a reference profile that consisted of either no infections or low
      intensity infection with only 1 parasite. Logistic regression models were used to
      quantify the effect that polyparasitism has on anemia (hemoglobin level <11
      g/dL). RESULTS: The odds of having anemia in children with low-intensity
      polyparasite infections were nearly 5-fold higher (P = .052) than those in
      children with the reference profile. The odds of having anemia in children
      infected with 3 or 4 parasite species at M+ intensity were 8-fold greater than
      those in children with the reference profile (P < .001). CONCLUSION: Low
      intensity polyparasite infections were associated with increased odds of having
      anemia. In most parts of the developing world, concurrent infection with multiple
      parasite species is more common than single-species infections. This study
      suggests that concurrent low-intensity infections with multiple parasite species
      result in clinically significant morbidity.

PMID- 16288384
TI  - Giardia assemblage A infection and diarrhea in Bangladesh.
AB  - Giardia lamblia is the most prevalent human intestinal protozoan worldwide, but
      only a minority of infections result in diarrhea. We tested here whether the 2
      major G. lamblia genotypes, assemblages A and B, differ in their propensity to
      cause disease. To determine whether an association exists between infection with
      assemblage A or B and diarrhea, 2534 Bangladeshi patients were enrolled in a case
      control study. A total of 322 Giardia infections were identified and assayed for
      genotype by real-time polymerase chain reaction. Higher odds ratios for diarrhea
      were observed for assemblage A and A2 infections, whereas higher parasite DNA
      loads and a higher overall prevalence were observed for assemblage B infections.
      Our findings indicate that genotypic differences in virulence and fecundity may
      help to explain why not every Giardia infection results in disease, but they need
      to be confirmed in other urban populations of the developing world.

PMID- 16288385
TI  - Insight into the early spread of chloroquine-resistant Plasmodium falciparum
      infections in Papua New Guinea.
AB  - The first report of Plasmodium falciparum chloroquine (CQ) resistance (CQR) in
      Papua New Guinea (PNG) appeared in 1974. Although the current prevalence of CQR
      associated parasite gene polymorphisms has been documented for some regions, the
      spatial and temporal relationships that characterize CQ-resistant parasites in
      PNG are unknown. Insight into the evolution of CQ-resistant parasites could be
      provided by evaluating genetic markers in parasite populations. We compared pfcrt
      and pfmdr1 polymorphisms and flanking microsatellite (MS) polymorphisms between
      P. falciparum-infected placental tissue (early 1980s) and blood (late 1990s)
      samples collected throughout PNG. Consistent with the results of recent studies,
      pfcrt-SVMNT and pfmdr1-86Y were the only CQR-associated alleles observed in the
      placental tissue samples, and they were observed together in 79% of the samples.
      Results of analysis of MS flanking pfcrt (approximately 40 kb) suggested that
      there was less diversity in the samples collected during the 1980s than in those
      collected during the 1990s and that the 1990s parasites were significantly
      differentiated from the 1980s parasites. On the other hand, for MS flanking
      pfmdr1 (approximately 5 kb) and for 1 putatively neutral locus, diversity levels
      were similar, and the 2 parasite populations were not significantly
      differentiated. These results suggest that selection for CQR was operating on the
      pfcrt-SVMNT allele during the early 1980s. Thus, archival samples can provide
      novel insight into the dynamics of CQR.

PMID- 16288386
TI  - Benefits of serologic screening for hepatitis B immunity in military recruits.

PMID- 16288388
TI  - The epidemiology of blastomycosis in Illinois and factors associated with death.
AB  - BACKGROUND: Blastomycosis is a systemic fungal disease that may be asymptomatic
      or progressive and may lead to death. METHODS: In response to a reported increase
      in the number of cases of blastomycosis in Illinois, surveillance data reported
      to the Illinois Department of Public Health from January 1993 to August 2003 were
      analyzed and the medical records of 4 patients who died were reviewed. RESULTS:
      Among the 500 cases reported, the median age of the patients was 43 years (range,
      4-87 years), and 34 patients (7%) died. Higher rates of mortality were observed
      among persons who were black, who were > or =65 years of age, and who were male.
      The median time from onset of illness to diagnosis was 128 days (range, 12-489
      days). Death was associated with a time from onset of illness to diagnosis of >
      or =128 days (OR, 2.1; 95% CI, 1.0-4.8). During the period from 1993 through
      2002, the number of cases reported per year increased from 24 to 87 (P<.05).
      CONCLUSIONS: The incidence of blastomycosis has been increasing in Illinois. To
      reduce mortality related to delay in diagnosis and treatment, medical providers
      need to be educated about blastomycosis, with an emphasis on symptom recognition,
      methods of diagnosis, and appropriate antifungal treatment.

PMID- 16288389
TI  - Lyme meningoradiculitis and myositis after allogeneic hematopoietic stem cell
      transplantation.
AB  - We describe a patient with a history of allogeneic hematopoietic stem cell
      transplantation complicated by chronic graft-versus-host disease who developed
      painful meningoradiculitis and myositis due to Lyme borreliosis. To our
      knowledge, this is the first report of such an infection occurring after
      allogeneic hematopoietic stem cell transplantation in the United States.

PMID- 16288390
TI  - Treatment with sequential intravenous or oral moxifloxacin was associated with
      faster clinical improvement than was standard therapy for hospitalized patients
      with community-acquired pneumonia who received initial parenteral therapy.
AB  - BACKGROUND: Although third-generation cephalosporins, such as ceftriaxone (CTRX),
      and pneumococcal fluoroquinolones, such as moxifloxacin (MXF), are currently
      recommended first-line antibiotics for empirical treatment of inpatients with
      community-acquired pneumonia, CTRX and MXF have never undergone a head-to-head
      comparison. We therefore compared the efficacy, safety, and speed and quality of
      defervescence of sequential intravenous or oral MXF and high-dose CTRX with or
      without erythromycin (CTRX+/-ERY) for patients with community-acquired pneumonia
      requiring parenteral therapy. METHODS: In this prospective, multicenter,
      randomized, controlled, nonblinded study, 397 patients were randomly assigned to
      receive either MXF (400 mg once daily intravenously, possibly followed by oral
      tablets) or CTRX (2 g intravenously once daily) with or without ERY (1 g
      intravenously every 6-8 h) for 7-14 days. RESULTS: Among 317 patients evaluable
      for efficacy and safety, 138 (85.7%) of 161 MXF-treated patients and 135 (86.5%)
      of 156 CTRX+/-ERY-treated patients (59 [37.8%] of whom received CTRX and ERY)
      achieved continued clinical resolution. Defervescence and relief of symptoms,
      such as chest pain, occurred significantly earlier in the MXF-treated group than
      in the CTRX+/-ERY-treated group. Both regimens were generally well tolerated.
      CONCLUSIONS: For adult patients hospitalized with community-acquired pneumonia,
      sequential MXF therapy was clinically equivalent to high-dose CTRX+/-ERY therapy
      but led to a faster clinical improvement.

PMID- 16288391
TI  - Optimizing therapy for community-acquired pneumonia with the goal of rapid
      resolution of illness.

PMID- 16288392
TI  - Antibiotic prescription for community-acquired pneumonia in the intensive care
      unit: impact of adherence to Infectious Diseases Society of America guidelines on
      survival.
AB  - BACKGROUND: The purpose of our study was to analyze prognostic factors associated
      with mortality for patients with severe community-acquired pneumonia (CAP).
      METHODS: We conducted a prospective multicenter study including all patients with
      CAP admitted to the intensive care unit during a 15-month period in 33 Spanish
      hospitals. Admission data and data on the evolution of the disease were recorded.
      Multivariate analysis was performed using the SPSS statistical package (SPSS).
      RESULTS: A total of 529 patients with severe CAP were enrolled; the mean age (+/
      SD) was 59.9+/-16.1 years, and the mean Acute Physiology and Chronic Health
      Evaluation (APACHE) II score (+/-SD) was 18.9+/-7.4. Overall mortality among
      patients in the intensive case unit was 27.9% (148 patients). The rate of
      adherence to Infectious Diseases Society of America (IDSA) guidelines was 57.8%.
      Significantly higher mortality was documented among patients with nonadherence to
      treatment (33.2% vs. 24.2%). Multivariate analysis identified age (odds ratio
      [OR], 1.7), APACHE II score (OR, 4.1), nonadherence to IDSA guidelines (OR, 1.6),
      and immunocompromise (OR, 1.9) as the variables present at admission to the
      intensive care unit that were independently associated with death in the
      intensive care unit. In 15 (75%) of 20 cases of Pseudomonas aeruginosa infection,
      the antimicrobial treatment at admission was inadequate (including 8 of 15 cases
      involving patients with adherence to IDSA guidelines). Chronic obstructive
      pulmonary disease (OR, 17.9), malignancy (OR, 11.0), previous antibiotic exposure
      (OR, 6.2), and radiographic findings demonstrating rapid spread of disease (OR,
      3.9) were associated with P. aeruginosa pneumonia. CONCLUSIONS: Better adherence
      to IDSA guidelines would help to improve survival among patients with severe CAP.
      Pseudomonas coverage should be considered for patients with chronic obstructive
      pulmonary disease, malignancy, or recent antibiotic exposure.

PMID- 16288393
TI  - The halo effect of adherence to guidelines extends to patients with severe
      community-acquired pneumonia requiring admission to an intensive care unit.

PMID- 16288394
TI  - Prevalence of BK virus replication among recipients of solid organ transplants.
AB  - BACKGROUND: BK virus (BKV) has been implicated as a cause of nephritis and graft
      loss in 2%-9% of kidney transplant recipients, but the prevalence among
      recipients of other solid organ transplants (SOTs) has not been well established.
      Our objective was to determine the prevalence of BKV infection for all types of
      SOT recipients at our medical center. METHODS: A total of 156 consecutive SOT
      recipients were studied, of whom 49 received kidney transplants, 43 received
      heart transplants, and 64 received liver transplants. Samples were obtained a
      median of 559 days (range, 1-9481 days) after transplantation. Nested polymerase
      chain reaction was performed for detection of BKV DNA in urine and plasma
      specimens. RESULTS: BKV was found in 19% of urine specimens and 6% of plasma
      specimens. The prevalence of viruria after kidney, heart, and liver
      transplantation was 26.5%, 25.5%, and 7.8%, respectively. BKV viremia was
      detected in 12.2% of kidney transplant recipients and 7% of heart transplant
      recipients. Mean creatinine levels were higher in patients with BKV viruria or
      viremia (1.9 and 3.5 mg/dL, respectively) than in patients with no BKV
      replication (1.3 mg/dL). Independent factors related to impaired renal function
      were renal transplantation (odds ratio [OR], 14.4); BKV replication, including
      viruria or viremia (OR, 3.3); and mycophenolate use (OR, 2.6). CONCLUSION: BKV is
      common in all types of SOT recipients, particularly those who have received heart
      or kidney transplants.

PMID- 16288395
TI  - BK virus and renal dysfunction: not limited to kidney transplantation?

PMID- 16288396
TI  - High-risk types of human papillomavirus (HPV) DNA in oral and genital mucosa of
      infants during their first 3 years of life: experience from the Finnish HPV
      Family Study.
AB  - BACKGROUND: This study is aimed to clarify data on the acquisition, persistence,
      and clearance of high-risk types of human papillomavirus (HPV) DNA from the
      mucosa and the determinants of persistent mucosal HPV infection in infants.
      METHODS: Oral and genital scrapings from 324 infants were collected at birth, 3
      days after delivery, and 1, 2, 6, 12, 24, and 36 months after delivery and tested
      for the presence of HPV DNA by nested polymerase chain reaction and hybridization
      with 12 high-risk HPV oligoprobes. HPV status and demographic data for parents
      were analyzed. RESULTS: During the follow-up period (median duration, 26.2
      months), HPV DNA was found to be present in 12%-21% of oral scrape samples and in
      4%-15% of genital scrape samples obtained from the infants. Oral HPV infection
      was acquired by 42% of children, cleared by 11%, and persisted in 10% of the
      infants, whereas 37% were never infected. The corresponding figures for genital
      HPV infection were 36%, 14%, 1.5%, and 47%. Kaplan-Meier analysis revealed that
      both the cumulative incidence of infection and clearance of HPV were parallel in
      oral and genital sites. Persistent oral HPV infection in the child was
      significantly associated with persistent oral HPV infection in the mother at
      month 36 of follow-up, hand warts in the mother, young age at onset of sexual
      activity for the mother, and the mother's use of oral contraception, as well as
      with the father's oral HPV status at 24 months. Persistent genital HPV infection
      in the infant was predicted by if the mother had started smoking at 18-21 years
      of age and by a history of genital warts. CONCLUSIONS: Persistent carriage of
      high-risk HPV types was detected in oral and genital mucosa specimens obtained
      from 10% and 1.5% of the infants during their first 26 months of life. The rates
      of acquisition and clearance of HPV were similar in oral and genital mucosa.

PMID- 16288397
TI  - Physicians' acceptable treatment failure rates in antibiotic therapy for
      coagulase-negative staphylococcal catheter-associated bacteremia: implications
      for reducing treatment duration.
AB  - BACKGROUND: Decreasing the duration of antimicrobial therapy is an attractive
      strategy for delaying the emergence of antimicrobial resistance. Limited data
      regarding optimal treatment durations for most clinical infections hinder the
      adoption of this approach and impair optimal physician-patient communication
      under the shared decision-making model. We aimed to identify acceptable failure
      rates among infectious disease consultants (IDCs) for treatment of central venous
      catheter-associated bacteremia. METHODS: A case scenario involving a
      representative patient who developed central venous catheter-associated
      bacteremia caused by coagulase-negative staphylococci and who received standard
      of-care therapy was distributed to all nonpediatric IDC members of the Infectious
      Diseases Society of America's Emerging Infections Network in August 2003. Each
      member was suggested 1 of 10 treatment failure rates and asked whether he or she
      would accept or reject the given value. Logistic regression was used to evaluate
      the relationship between specific failure rates offered to respondents and their
      willingness to accept them using a methodology derived from contingent valuation.
      RESULTS: Among the 374 respondents (response rate, 54%), the median acceptable
      failure rate was 6.8%. Thus, one-half of the IDCs would have found a failure rate
      of 6.8% to be acceptable. Seventy-five percent of IDCs would have found a failure
      rate of 1.6% to be acceptable, and 25% of IDCs would have found a failure rate as
      high as 11.9% to be acceptable. CONCLUSIONS: The quantified acceptable failure
      rates, when used to interpret clinical trial or cohort study results, will help
      select optimal antimicrobial therapy durations for this specific condition. These
      findings are a critical step in the development of effective shared decision
      making models.

PMID- 16288398
TI  - Clinical characteristics of human monkeypox, and risk factors for severe disease.
AB  - BACKGROUND: Human monkeypox is an emerging smallpox-like illness that was
      identified for the first time in the United States during an outbreak in 2003.
      Knowledge of the clinical manifestations of monkeypox in adults is limited, and
      clinical laboratory findings have been unknown. METHODS: Demographic information;
      medical history; smallpox vaccination status; signs, symptoms, and duration of
      illness, and laboratory results (hematologic and serum chemistry findings) were
      extracted from medical records of patients with a confirmed case of monkeypox in
      the United States. Two-way comparisons were conducted between pediatric and adult
      patients and between patients with and patients without previous smallpox
      vaccination. Bivariate and multivariate analyses of risk factors for severe
      disease (fever [temperature, > or =38.3 degrees C] and the presence of rash [> or
      =100 lesions]), activity and duration of hospitalization, and abnormal clinical
      laboratory findings were performed. RESULTS: Of 34 patients with a confirmed case
      of monkeypox, 5 (15%) were defined as severely ill, and 9 (26%) were hospitalized
      for >48 h; no patients died. Previous smallpox vaccination was not associated
      with disease severity or hospitalization. Pediatric patients (age, < or =18
      years) were more likely to be hospitalized in an intensive care unit. Nausea
      and/or vomiting and mouth sores were independently associated with a
      hospitalization duration of >48 h and with having > or =3 laboratory tests with
      abnormal results. CONCLUSION: Monkeypox can cause a severe clinical illness, with
      systemic signs and symptoms and abnormal clinical laboratory findings. In the
      appropriate epidemiologic context, monkeypox should be included in the
      differential diagnosis for patients with unusual vesiculopustular exanthems,
      mucosal lesions, gastrointestinal symptoms, and abnormal hematologic or hepatic
      laboratory findings. Clinicians evaluating a rash illness consistent with
      possible orthopoxvirus infection should alert public health officials and
      consider further evaluation.

PMID- 16288399
TI  - Pneumocystis carinii: has the name really been changed?
AB  - The proposed renaming of Pneumocystis carinii has caused much confusion and
      controversy among authors, peer reviewers, editors, and interested readers.
      Proponents of the new nomenclature emphasize the fact that the new names are
      judged to be "valid" by the International Code of Botanical Nomenclature. What is
      generally not appreciated is the fact that the International Code of Botanical
      Nomenclature does not make any determination as to the scientific correctness of
      proposed names; rather, it mandates the process of naming an organism. Thus,
      acknowledgement by the International Code of Botanical Nomenclature that new
      names for P. carinii have been validly published does not mandate their use.
      Rather, the scientific community interested in P. carinii needs to be aware of
      the issues involved in changing the name and then decide for themselves as to the
      correctness of the newly proposed names. Use of the newly proposed names for P.
      carinii should not be mandated by journal reviewers or editors.

PMID- 16288400
TI  - Has the name really been changed? It has for most researchers.

PMID- 16288401
TI  - Wind, rain, flooding, and fear: coordinating military public health in the
      aftermath of Hurricane Katrina.
AB  - On 29 August 2005, a category 4 hurricane struck the Gulf Coast of Mississippi
      and southeast Louisiana, resulting in widespread destruction caused by winds in
      excess of 190 km/h (120 miles/h), heavy rain, and flooding. Communication,
      electricity, and fresh water supplies were disrupted throughout the region,
      rendering much of the area uninhabitable. Despite tremendous obstacles, the US
      military spearheaded the eventually successful rescue, recovery, and relief
      operations. This article describes the challenges of protecting the health and
      safety of these personnel in the immediate aftermath of Hurricane Katrina.

PMID- 16288402
TI  - Reemergence of monkeypox: prevalence, diagnostics, and countermeasures.
AB  - Human monkeypox is a viral zoonotic disease that occurs mostly in the rain
      forests of central and western Africa. However, the disease recently emerged in
      the United States in imported wild rodents from Africa. Monkeypox has a clinical
      presentation very similar to that of ordinary forms of smallpox, including
      flulike symptoms, fever, malaise, back pain, headache, and characteristic rash.
      Given this clinical spectrum, differential diagnosis to rule out smallpox is very
      important. There are no licensed therapies for human monkeypox; however, the
      smallpox vaccine can protect against the disease. The discontinuation of general
      vaccination in the 1980s has given rise to increasing susceptibility to monkeypox
      virus infection in the human population. This has led to fears that monkeypox
      virus could be used as a bioterrorism agent. Effective prevention relies on
      limiting the contact with infected patients or animals and limiting the
      respiratory exposure to infected patients.

PMID- 16288403
TI  - Incidence of Tuberculosis among HIV-infected patients receiving highly active
      antiretroviral therapy in Europe and North America.
AB  - BACKGROUND: We obtained estimates of the incidence of tuberculosis (TB) among
      patients receiving HAART and identified determinants of the incidence. METHODS:
      We analyzed the incidence of TB during the first 3 years after initiation of
      HAART among 17,142 treatment-naive, AIDS-free persons starting HAART who were
      enrolled in 12 cohorts from Europe and North America. We used univariable and
      multivariable Poisson regression models to identify factors associated with the
      incidence. RESULTS: During the first 3 years (36,906 person-years), 173 patients
      developed TB (incidence, 4.69 cases per 1000 person-years). In multivariable
      analysis, the incidence rate was lower for men who have sex with men, compared
      with injection drug users (relative rate, 2.46; 95% confidence interval [CI],
      1.51-4.01), heterosexuals (relative rate, 2.42; 95% CI, 1.64-3.59), those with
      other suspected modes of transmission (relative rate, 1.66; 95% CI, 0.91-3.06),
      and those with a higher CD4+ count at the time of HAART initiation (relative rate
      per log2 cells/microL, 0.87; 95% CI, 0.84-0.91). During 28,846 person-years of
      follow-up after the first 6 months of HAART, 88 patients developed TB (incidence,
      3.1 cases per 1000 person-years of follow-up). In multivariable analyses, a low
      baseline CD4+ count (relative rate per log2 cells/microL, 0.89; 95% CI, 0.83
      0.96), 6-month CD4+ count (relative rate per log2 cells/microL, 0.90; 95% CI,
      0.81-0.99), and a 6-month HIV RNA level >400 copies/mL (relative rate, 2.21; 95%
      CI, 1.33-3.67) were significantly associated with the risk of acquiring TB after
      6 months of HAART. CONCLUSION: The level of immunodeficiency at which HAART is
      initiated and the response to HAART are important determinants of the risk of TB.
      However, this risk remains appreciable even among those with a good response to
      HAART, suggesting that other interventions may be needed to control the TB
      epidemic in the HIV-infected population.

PMID- 16288404
TI  - Incidence of tuberculosis during highly active antiretroviral therapy in high
      income and low-income countries.

PMID- 16288405
TI  - Efficacy of cerebrospinal fluid (CSF)-penetrating antiretroviral drugs against
      HIV in the neurological compartment: different patterns of phenotypic resistance
      in CSF and plasma.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) concentrations of multiple drugs in a large
      human immunodeficiency virus (HIV)-infected patient population, the virtual
      phenotype profiles for HIV in the plasma and CSF compartments, and the
      correlation of these profiles with exposure to antiretroviral therapy need to be
      further investigated. METHODS: Drug concentrations in CSF and plasma were
      concomitantly determined for a large group of HIV-infected individuals receiving
      highly active antiretroviral therapy (HAART). Samples were analyzed using a
      validated method consisting of liquid chromatography with mass spectrometry. For
      patients with detectable levels of virus, genotypic analysis was performed,
      followed by a virtual phenotype study. RESULTS: Sixty-three HIV-infected patients
      were included in the study, 78% of whom were affected by neurological disease.
      Drug concentrations in CSF specimens were undetectable for didanosine, efavirenz,
      nelfinavir, and concomitantly administered ritonavir and saquinavir. CSF
      concentrations were higher for nevirapine, with a median CSF-to-plasma
      concentration ratio of 0.63, followed by lamivudine (0.23), stavudine (0.20), and
      indinavir (0.11). In 18 of the 40 patients with virtual phenotype data available
      for virus recovered from CSF samples and from plasma samples, differences in fold
      change of resistance between the CSF virus and the plasma virus were noted for at
      least 1 drug. Factors associated with having differences in fold-change of
      resistance were number of drugs to which the patient had been exposed (P=.02) and
      presence of neurological disease (P=.05). A significant association was found
      between duration of therapy and fold-change of resistance in CSF and plasma
      isolates. CONCLUSIONS: Antiretrovirals have different levels of penetration in
      the CSF, with several drugs achieving only low CSF concentrations. CSF isolates
      have different resistance profiles than do plasma isolates. Effective treatment
      decisions for CSF manifestations of disease may require better knowledge of drug
      penetration and the drug susceptibility of HIV in the CSF.

PMID- 16288406
TI  - Androgen levels in older men who have or who are at risk of acquiring HIV
      infection.
AB  - OBJECTIVE: To determine the prevalence of, risk factors for, and clinical
      manifestations of low androgen levels in older men who have or who are at risk of
      acquiring human immunodeficiency virus (HIV) infection, we performed a cross
      sectional analysis of an observational cohort of men aged > or =49 years old.
      METHODS: A standardized interview (regarding demographic characteristics,
      behaviors, and medical history) was performed, and body mass index, HIV serologic
      data, CD4+ cell count, the presence of hepatitis C virus (HCV) markers, and serum
      testosterone and human sex-binding hormone levels were determined. Factors
      associated with androgen levels were assessed using logistic regression models.
      RESULTS: Among 502 men (age, 49-81 years) who were not taking androgens, 54% had
      total testosterone levels of <300 ng/dL. Low androgen levels were associated with
      injection drug use, HCV infection, high body mass index, and use of psychotropic
      medications (P<.05); black race was associated with higher androgen levels. Only
      among men who reported having sex with men was low testosterone level associated
      with HIV infection (adjusted odds ratio [OR(adj)] for total testosterone level of
      <300 ng/dL, 5.1; 95% confidence interval [CI], 1.2-22.4), but among all HIV
      seropositive men, HIV load of >10,000 copies/mL was associated with a
      testosterone level of <200 ng/dL (OR(adj), 2.1; 95% CI, 1.1-4.3; P=.03). On
      univariate analysis, low androgen levels were associated with decreased interest
      in sex, depressive symptoms, loss of concentration/memory, difficulty sleeping,
      osteopenia, and poorer subjective health (P<.05). CONCLUSIONS: Most older men at
      risk for HIV infection have low androgen levels. Injection drug use, high body
      mass index, HCV infection, and use of psychotropic medications are associated
      with low androgen levels, and low androgen levels are associated with symptoms of
      hypogonadism.

PMID- 16288407
TI  - Androgen deficiency and HIV infection.

PMID- 16288408
TI  - Spontaneous hepatic decompensation in patients coinfected with HIV and hepatitis
      C virus during interferon-ribavirin combination treatment.
AB  - Spontaneous hepatic decompensation was observed in 7 of 383 patients coinfected
      with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who were
      receiving treatment with interferon and ribavirin. Multivariate analysis
      identified the following risk factors: didanosine use (odds ratio [OR], 8.8; 95%
      confidence interval [CI], 1.2-102.3; P < .02), cirrhosis, (OR, 8.8; 95% CI, 1.2
      104.2; P<.02), and elevated total bilirubin level (OR, 7.9; 95% CI, 1.08-93.3;
      P<.03). Didanosine should thus not be given to patients with cirrhosis,
      particularly when treatments for HCV and HIV infections have to be administered
      concomitantly.

PMID- 16288409
TI  - Clinical and in vitro evaluation of cidofovir for treatment of adenovirus
      infection in pediatric hematopoietic stem cell transplant recipients.
AB  - Post-hematopoietic stem cell transplantation (HSCT) adenovirus infections were
      identified in 31 of 204 consecutive pediatric HSCT patients, 18 of whom had
      severe manifestations of infection. Cidofovir treatment led to clinical
      improvement in 8 of 10 patients with severe infection and to virologic clearance
      in 9 patients. In vitro susceptibility to cidofovir was demonstrated in 12
      clinical adenovirus isolates. Cidofovir is a promising treatment option for this
      population.

PMID- 16288410
TI  - A polymorphism of intercellular adhesion molecule-1 is associated with a reduced
      incidence of nonmalarial febrile illness in Kenyan children.
AB  - An intercellular adhesion molecule-1 polymorphism (ICAM-1(Kilifi)) is present at
      a high frequency across sub-Saharan Africa, and its presence may increase
      susceptibility to cerebral malaria. Here, we report that, compared with children
      in whom wild-type intercellular adhesion molecule-1 is present, the incidence of
      nonmalarial fever is significantly lower among those homozygous for ICAM
      1(Kilifi). We propose that ICAM-1(Kilifi) may be associated with reduced rates of
      tissue damage and of death due to sepsis.

PMID- 16288411
TI  - Seroreversion in children infected with HIV type 1 who are treated in the first
      months of life is not a rare event.

PMID- 16288412
TI  - Invasive pneumococcal disease in children: changing serotypes and clinical
      expression of disease.

PMID- 16288414
TI  - Rapid development of auricular infection due to imipenem-resistant Pseudomonas
      aeruginosa following self-administered piercing of high ear.

PMID- 16288415
TI  - Gatifloxacin therapy for children: turn on the light.

PMID- 16288416
TI  - Albendazole for the treatment of anisakiasis ileus.

PMID- 16288417
TI  - False-positive serological test results for Lyme disease in a patient with acute
      herpes simplex virus type 2 infection.

PMID- 16288418
TI  - [Neurologic manifestations of infective endocarditis: a diagnostic and prognostic
      challenge].
AB  - INTRODUCTION: Infective endocarditis (IE) is an ongoing challenge in terms of
      excess morbidity and mortality. Neurologic complications occur in 20-40% of
      patients, and the brain is the main location of IE extracardiac complications.
      AIM: To analyse clinical characteristics of the neurologic complications found in
      patients with IE, focused on the diagnostic and prognostic aspects. PATIENTS AND
      METHODS: We studied retrospectively the cases of patients with IE admitted to the
      Hospital de Valme and Hospital de la Merced between 1998 and 2003. Laterly,
      patients with and without neurologic manifestations were compared. Sixty episodes
      of IE were evaluated. RESULTS: Neurological complications occurred in 12 patients
      (20%). The most frequent neurologic manifestation was unilateral hemi paresis,
      which occurred in seven cases (58.3%), three cases with acute confusional state
      (25%) and two patients developed meningitis (16.6%). Brain infarction was the
      most common lesion found in neuroimaging, in 6 patients (50%), followed by 2
      cases (16.6%) of brain hemorrhage, and without significant findings in the cases
      left. Cases with neurologic complications had significantly higher mortality (p <
      0.001) and higher frequency of negative blood culture (p < 0.001). CONCLUSIONS:
      Neurologic complications of IE are frequent during the evolution of the disease,
      and they still constitute a significant problem in clinical practice because they
      often are not accurately diagnosed and significantly increase patients'
      mortality.

PMID- 16288419
TI  - [Lowered incidence of post-lumbar puncture headache following the application of
      the second edition of the International Headache Society classification].
AB  - INTRODUCTION: In 1988 the International Headache Society (IHS) published the 1st
      edition of its headache classification and the 2nd edition was completed in 2003.
      AIM. To determine whether there exist changes in the incidence of post-lumbar
      puncture headache depending on the edition of the IHS classification. PATIENTS
      AND METHODS: Between 2002 and 2003 data was gathered prospectively for 78
      patients who were submitted to a diagnostic lumbar puncture, 40 obstetric spinal
      anaesthesias and 516 non-obstetric spinal anaesthesias. The 1st edition was used
      and, after the appearance of the 2nd edition, the cases were recoded. RESULTS:
      With the 1st edition, there were 31 out of 78 cases (39.7%) of post-puncture
      headache in diagnostic punctures, and when the 2nd edition was used, the number
      dropped to 10 cases (12.8%). The incidence of headache among patients who had
      undergone obstetric spinal anaesthesia was six cases out of a total of 40 (15%)
      using the 1st edition, and four cases with the 2nd edition (10%). The incidence
      of headache among patients after non-obstetric spinal anaesthesia was 80 cases
      out of a total of 516 (15.5%) when the 1st edition was utilised and 25 cases with
      the 2nd edition (4.85%). CONCLUSIONS: To compare the incidences of post-lumbar
      puncture headaches obtained by diverse observers we need to know which edition
      was used, since there are considerable differences between the results obtained
      using one edition or the other. The main reason accounting for the discrepancy
      between the two editions is the compulsory association of some accompanying sign,
      since this was not a necessary criterion in the 1st edition but it is included in
      the 2nd.

PMID- 16288420
TI  - [Results of screening for symptoms of attention deficit disorder with or without
      hyperactivity in schools by means of the ADHS scale].
AB  - INTRODUCTION: The diagnosis of attention deficit disorder with or without
      hyperactivity (ADHD) is a controversial process that may be conditioned to a
      certain extent by the system of diagnostic classification, by the measuring
      instrument, by the population that has been chosen for study and by the source of
      information. This disparity among factors is clearly visible in epidemiological
      studies, where the rate of prevalence varies so much that it ranges from 1 to
      30%, although most studies place it somewhere between 3 and 5%. AIMS: To study
      the value of the attention deficit hyperactivity disorder rating scale (ADHS) as
      an instrument for screening for symptoms of ADHD in schools. SUBJECTS AND
      METHODS: The sample taken for study included 2,401 schoolchildren of both sexes
      between 6-12 years old from 10 different educational centres in Barcelona and the
      area of Valles Occidental. RESULTS: The analysis of the data obtained showed that
      12% of the subjects in our sample were at risk of ADHD, which means that one out
      of every eight schoolchildren could have this disorder. Boys scored consistently
      higher than girls in almost all of the subscales of the ADHS, the proportion
      being 4:1. CONCLUSIONS: Given the prevalence of this phenomenon, the authors
      suggest that further studies should be conducted to determine the prevalence of
      the disorder as a diagnostic condition.

PMID- 16288421
TI  - [Multiple sclerosis in Peru. A clinical-epidemiological description of a series
      of patients].
AB  - INTRODUCTION: In Peru up to recent years multiple sclerosis (MS) was considered a
      very rare disorder. AIM. To report clinical, epidemiological and ancillary test
      results of an MS cases series. PATIENTS AND METHODS: Description of a
      retrospective cohort of 55 patients studied in HNCH and a private neurological
      center in Lima between 1993-2004. Clinical records, laboratory and MRI tests were
      reviewed with Mc Donald's criteria. RESULTS: There were 55 cases (36 women). Mean
      age was forty. 65% were born in Lima, 27% have foreign ancestor up to third
      generation. 42 cases were definite MS and 13 possible MS. The most frequent form
      of MS was RRMS (49.1%). Early symptoms were optic neuritis, motor and sensitive
      complaints; in the follow up cerebelar symptoms, increase of motor compromise and
      sphincteric disturbance were showed. Brain and spine MRI were positive in 27
      cases and 17 cases respectively. VEP were abnormal in 53% of cases, just one case
      had cerebrospinal fluid (CSF) compatible with MS. Mode of EDSS was 6.5.
      Immunomodulators were used in 30% of cases. Survival at 10 and 20 years of
      disease were 87% and 45% respectively. CONCLUSION: Our study shows than optic
      neuritis is an important early symptom and CSF study is commonly negative in
      patients with MS. Survival is shorter than other reports. Other features
      resembled previous international reports. To have foreign ancestors could be a
      risk factor for MS in this group.

PMID- 16288422
TI  - [Chronic relapsing axonal neuropathy. A case report].
AB  - INTRODUCTION: Polyneuropathies (PNP) result from damage to a number of nerves.
      They are classified according to the anatomical-functional, histological,
      aetiological and genetic characteristics. Here we report on the prolonged follow
      up carried out on an adult male who had a chronic recurring axonal-type PNP. CASE
      REPORT: We describe the case of a 65-year-old male who presented episodes of
      neurological deficit over a period of 10 years that were interspersed with
      prolonged, stable periods in which he was free of new symptoms. The patient's
      functional limitations became greater with each successive relapse and the
      situation is now one of extreme disability. The characteristics of the clinical
      picture pointed towards a diffuse peripheral nerve disorder, and the
      neurophysiological studies carried out revealed polyneuropathic, sensory and
      motor injury mediated by an axonal mechanism with no associated demyelination. A
      comprehensive analytical, imaging and functional study was conducted, but did not
      reveal any specific causes. The particular clinical process, the exclusion of
      other pathologies and the electrophysiological findings allowed us to reach a
      diagnosis of recurring or episodic chronic primary axonal PNP. CONCLUSIONS: This
      description can be added to the few cases reported in the literature. As we see
      it, this is an unusual, although probably underdiagnosed, disease and it must be
      taken into account in the differential diagnosis of chronic recurring PNP because
      of the diagnostic implications and--with respect to its usually poor response to
      therapy--due to the prognoses.

PMID- 16288423
TI  - [Aphasia and parietal syndrome as the presenting symptoms of a demyelinating
      disease with pseudotumoral lesions].
AB  - INTRODUCTION: Multiple sclerosis (MS) often presents with sensory symptoms, which
      are usually due to spinothalamic or spinal cord disorders; parietal syndrome is,
      however, very rare as the initial symptom. Likewise, aphasia is also an
      infrequent symptom of MS; in the few cases that have been reported, it is usually
      linked to the existence of important pseudotumoral lesions. CASE REPORT: We
      describe the case of a 31-year-old female with a 48-hour history of a progressive
      clinical picture consisting in nominal aphasia and a sensory parietal syndrome.
      Magnetic resonance imaging showed a lesion 3.6 cm in diameter that was
      hyperintense in T2 with perilesional edema and minimal gadolinium uptake, along
      with other images that revealed increased signal intensity in the periventricular
      subcortical white matter on the right-hand side and in the left-hand frontal
      subcortical region. A spectroscopic analysis of the largest lesion revealed that
      this lesion showed evidence of inflammation, with cell destruction and
      replacement, although it was not possible to distinguish between a demyelinating
      disease and a high grade glioma. Hence, a brain biopsy was required in order to
      reach the final diagnosis of demyelinating pseudotumoral lesion. CONCLUSIONS:
      Giant pseudotumoral plaques are a rare form of presenting symptom in MS; use of
      the clinical features, simple images and spectroscopy is not a very reliable
      means of reaching a differential diagnosis with a tumour and this often makes it
      necessary to conduct a biopsy study of the lesion.

PMID- 16288424
TI  - [Cell therapy and other neuroregenerative strategies in Parkinson's disease (I)].
AB  - OBJECTIVE: To review, from a mainly clinical standpoint, the different strategies
      applied to regenerate or restore the nigrostriatal dopaminergic system in
      Parkinson's disease. This first part focuses on the results of adrenal medulla
      and human fetal mesencephalic transplants, and a second part will address
      transplants of other cell types, administration of trophic factors, and gene
      therapy. DEVELOPMENT: Adrenal medulla transplants were abandoned because of their
      inconsistent results and high morbidity. Although fetal mesencephalic
      transplantation can produce long-term restoration of striatal dopamine
      deficiency, this neurochemical effect is clinically inadequate in presence of
      progressive neuronal loss. Other strategies with similar 'dopaminergic' action
      mechanism are not a therapeutic option in this setting. CONCLUSIONS: The
      objective of neuroregenerative therapy for Parkinson's disease should include
      trophic restoration of damaged neuronal systems, since improvement in striatal
      dopaminergic function is not sufficient. After the recent failure of the direct
      (intraventricular or intraputaminal) administration of glial cell line-derived
      neurotrophic factor (GDNF), attention of researchers has focused on indirect
      methods, including transplantation of GDNF-producing cells (carotid body cell
      aggregates or different genetically modified cells, including stem cells), and in
      vivo gene therapy.

PMID- 16288425
TI  - [Sneezing. A review of its causation and pathophysiology].
AB  - AIMS: To review some of the lesser known aspects of sneezing, which is a
      universal phenomenon suffered the world over but which has received little
      attention in the medical literature and especially by that dealing with
      neurology. DEVELOPMENT: Here we consider the causation, neurophysiology,
      pathophysiology, diagnosis and treatment of this reflex action, which sometimes
      goes beyond being just a simple ailment of little importance and becomes a sign
      associated to a series of different medical conditions. CONCLUSIONS: Despite its
      being such a commonplace occurrence, little is known about sneezing and few
      studies have been conducted to further our knowledge on the subject. Today there
      are still reports of cases of pathological sneezers, who often respond poorly to
      different treatments and for whom this reflex paroxysm becomes both a social and
      a health problem. Moreover, sneezing is sometimes associated with severe
      secondary medical sequelae. In contrast, there have also been reports of
      conditions in which the first symptom was an inability to sneeze. A thorough
      knowledge of this reflex, its causes and associated phenomena can be a valuable
      aid in the diagnosis of other concomitant diseases.

PMID- 16288426
TI  - [Balint's syndrome due to sequential bilateral haematomas].

PMID- 16288428
TI  - [Physiological variations in ERP300 auditory brain potentials in young adults. A
      sequential analysis].

PMID- 16288429
TI  - [Modification of the power distribution according to the consolidation of
      implicit memory by means of a typing task].

PMID- 16288430
TI  - [SUNCT syndrome secondary to megadolichobasilar anomaly].

PMID- 16288431
TI  - [Whole-body positron emission tomography: should official regulations be urgently
      changed?].

PMID- 16288432
TI  - New ideas in science and medicine and the renal control of acid-base balance.

PMID- 16288433
TI  - Plasma acid-base changes in chronic renal failure: a Stewart analysis.
AB  - The bicarbonate centered approach to acid-base physiology involves complex
      explanations for the metabolic acidosis associated with chronic renal failure. We
      used the alternate Stewart approach to acid-base physiology to quantify the acid
      base chemistry of patients with chronic renal failure. We examined the plasma and
      urine chemistry of 19 patients with chronic renal failure who were predialysis
      and 20 healthy volunteers. We compared the plasma strong-ion-difference due to
      sodium,potassium,and chloride ions as well as the weak acids albumin and
      phosphate. We used a simplified Fencl-Stewart approach to quantify the effects of
      sodium-chloride, albumin, and unmeasured ions on base-excess. The chronic renal
      failure group had a greater metabolic acidosis, with a base-excess that differed
      from the healthy group by a mean of -2.7 mmol/L, p = 0.04. This was associated
      with a strong ion acidosis due to both increased chloride and decreased sodium.
      The anion gap, strong-ion-gap, and base-excess effect of unmeasured ions were
      similar in both groups suggesting that unmeasured ions had only a minor role in
      the acid-base status in this group of patients.

PMID- 16288434
TI  - Dialytic performance evaluation of Rexeed: a new polysulfone-based dialyzer with
      improved flow distributions.
AB  - New dialyzers are designed to optimize the convective and diffusive components of
      solute transport. Asahi Kasei Medical Co.,Ltd.has developed a new high flux
      dialyzer series called Rexeed with improved flow distributions. We evaluated the
      in vivo dialytic performance of two dialyzers of the Rexeed series: Rexeed-18A
      and Rexeed-25A (1.8 m2 and 2.5 m2 ). We calculated the clearance for
      urea,creatinine,phosphate and b2-microglobulin both in high flux dialysis
      (HFD)and in 15 liter postidiluitional on-line hemodiafiltration (HDF)mode. With n
      = 3 patients in high flux HD at blood flow 450, 400, 350 and 250 ml/min we found
      remarkably high clearance for urea (347 +/- 4%, 305 +/- 0%, 288 +/- 5%, 230 +/-
      3%, for Rexeed-18A and 361 +/- 3%, 329 +/- 0%, 313 +/- 1%, 234 +/- 3%for Rexeed
      25A),creatinine (282 +/- 10%, 234 +/- 0%, 221 +/- 8%, 174 +/- 8%, for Rexeed-18A
      and 276 +/- 6%, 245 +/- 0%, 226 +/- 9%, 172 +/- 13% for Rexeed-25A),phosphate
      (347 +/- 0%, 316 +/- 0%, 275 +/- 4%, 202 +/- 16%, for Rexeed-18A and 364 +/- 3%,
      365 +/- 0%,286 +/- 3%, 224 +/- 2% for Rexeed-25A)and b2-microglobulin (133 +/-
      21%, 124 +/- 0%,118 +/- 12%, 98 +/- 11%, for Rexeed-18A and 159 +/- 8%, 169 +/-
      0%,157 +/- 8%, 129 +/- 7% for Rexeed-25A) With n = 2 patients in HDF at blood
      flow 300 ml/min we found remarkably high clearance for urea (268 +/- 2%, for
      Rexeed-18A and 283 +/- 2% for Rexeed-25A),creatinine (183 +/- 6%for Rexeed-18A
      and 205 +/- 9% for Rexeed-25A),phosphate (245 +/- 3%, for Rexeed-18A and 270 +/-
      2% for Rexeed-25A)and b2-microglobulin (166 +/- 12%, for Rexeed-18A and 192 +/-
      4% for Rexeed-25A). Our preliminary evaluation describes the characteristics and
      the performances of a new polysulfone-based hemodialyzer series called Rexeed.
      Several innovative features have been implemented by the manufacturer. These
      constructive approaches seem to have produced a positive effect on the dialyzer
      performance at the bedside.

PMID- 16288435
TI  - Fluid and solute transport in CAPD patients before and after permanent loss of
      ultrafiltration capacity.
AB  - BACKGROUND: Two major types of permanent loss of ultrafiltration capacity (UFC)
      were previously distinguished among patients treated with CAPD: 1) type HDR with
      high diffusive peritoneal transport rate of small solutes and low osmotic
      conductance,but with normal fluid absorption rate, and 2) type HAR with high
      fluid absorption rate, but with normal diffusive peritoneal transport rate of
      small solutes and normal osmotic conductance. However, the detailed pattern of
      changes in peritoneal transport parameters in patients developing loss of
      ultrafiltration capacity is not known. OBJECTIVE: Analysis of solute and fluid
      transport parameters in the same patient before and after UFC loss. PATIENTS:
      Seven CAPD patients who had undergone repeated dwell studies,which were carried
      out before and/or after the onset of UFC loss. METHODS: Dialysis fluids (2 L)
      with glucose or a mixture of amino acids as osmotic agent at three basic
      tonicities were applied during 6 hour dwell studies. Fluid and solute transport
      parameters were previously shown not to be affected by these dialysis solutions
      (except by hypertonic amino acid-based solution). Intraperitoneal dialysate
      volume and fluid absorption rate were assessed using radiolabeled human serum
      albumin (RISA). Osmotic conductance (a(OS))was estimated by a mathematical model
      as ultrafiltration rate induced by unit osmolality gradient. Diffusive mass
      transport coefficients, K(BD), for glucose,urea,and creatinine were estimated
      using the modified Babb-Randerson-Farrell model. RESULTS: Five patients had
      increased K(BD) for small solutes after the onset of UFC loss,and three of them
      had decreased a(OS),whereas two patients had normal a(OS). In one of them, a(OS)
      decreased with time after the onset of UFC loss with concomitant normalization of
      glucose absorption. In all studies of these five patients the fluid absorption
      rate was within the normal range. Two other patients had increased fluid
      absorption rate (about 5 ml/min),and one of them also had increased K(BD) for
      small solutes,in two consecutive dwell studies in each patient with the second
      study being carried out at 1 and 7 months respectively after the first one. In
      all four studies in these two patients, the a(OS) was within the normal range.
      The sodium dip during dialysis with 3.86% glucose-based solution was lost, not
      only among most patients with UFC loss related to reduced osmotic conductance,
      but also in patients with increased K(BD). CONCLUSIONS: The occurrence of two
      major types of UFC loss was confirmed. However, a case of a mixed type of UFC
      loss with high fluid absorption rate and high K(BD) for small solutes, but normal
      osmotic conductance, and with normalization of initially high K(BD) for small
      solutes, linked with decreasing initially normal osmotic conductance,was also
      found. As a reduced sodium dip with hypertonic glucose solution is not only seen
      in patients with reduced osmotic conductance, it cannot reliably be used as a
      single measure of decreased aquaporin function. Permanent ultrafiltration
      capacity loss may be a dynamic phenomenon with a variety of alterations in
      peritoneal transport characteristics.

PMID- 16288436
TI  - Ex vivo evaluation of a new extracorporeal lung assist device: NovaLung membrane
      oxygenator.
AB  - When lung function is compromised,alternative devices need to be deployed in
      order to maintain blood oxygenation. A new device, NovaLung, has been designed
      for acute lung failure. We went about evaluating its gas exchange capability.
      Three calves (79.5 +/- 7.8 kg) were connected to the NovaLung System with a
      priming volume of 240 mL, gas exchange surface area of 1.3 m2 and exhibiting a
      biologically coated surface. A standard battery of blood samples were taken
      before implantation and over a six hour period. Hematocrit remained stable
      ranging from 27 +/- 4% (baseline) to 29 +/- 5% (6 hrs). Platelets were preserved
      ranging from 882 +/- 27.4 U/L (baseline) to 734 +/- 147 (6 hrs). LDH remained
      stable at 719 +/- 85 U/L (baseline) vs 686 +/- 190 U/L (6 hrs) and the pressure
      drop was maintained below 20 mmHg. Minimal hemolysis was observed. Oxygen
      transfer peaked at two hours acute extracorporeal lung support (ECLS)with a mean
      value of 130 +/- 50 ml/min. In conclusion, the device is easy to use,provides
      adequate O2 and CO2 transfer for partial lung support in an acute setting. Shows
      minimal signs of hemolysis and platelets levels are maintained throughout the six
      hour ECLS period.

PMID- 16288437
TI  - PPS-PEG surface coating to reduce thrombogenicity of small diameter ePTFE
      vascular grafts.
AB  - AIMS: Patency failure of small vascular synthetic grafts is still a major problem
      for coronary and peripheral revascularization. Thus, three new surface coatings
      of small synthetic grafts were tested in an acute pig model to evaluate their
      thrombogenicity (extracorporeal arterio-venous shunt) and in a chronic rat model
      to evaluate the tissue reaction they induced (subcutaneous implantation).
      METHODS: In five domestic pigs (25-30 kg) an extracorporeal femoro-femoral
      arterio-venous shunt model was used. The study protocol included first a non
      heparinized perfusion sequence followed by graft perfusion after 10,000 UI iv
      heparin. Grafts were perfused for 3 and 9 minutes. The following coatings were
      tested on ePTFE grafts: poly-propylene sulphide (PPS)--poly-ethylene glycol (PEG)
      (wet and dry applications) as well as carbon. Two sets of control were used, one
      dry and one wet (vehicle only). After perfusion grafts were examined by scanning
      electron microscopy for semi-quantitative assessment (score 0-3) of cellular and
      microthrombi deposition. To assess tissue compatibility, pieces of each material
      were implanted subcutaneously in 16 Wistar rats. At 2, 4, 8, 12 weeks four
      animals each were sacrificed for semi-quantitative (score 0-3) histologic
      evaluation of tissue reaction. RESULTS: In the pig model, cellular deposition and
      microthrombi formation increased over time. In non- heparinized animals, the
      coatings did not improve the surface characteristics, since they did not prevent
      microthrombi formation and cellular deposition. In heparinized animals,
      thrombogenicity was lowest in coated grafts,especially in PPS -PEG dry (p<0.05),
      and highest in controls. Cell deposition was lowest in PPS-PEG dry, but this
      difference was not statistically significant vs.controls. In the rat model,no
      significant differences of the tissue reaction could be shown between materials.
      CONCLUSION: While all coatings failed to add any benefit for lowering tissue
      reaction, surface coating with PPS -PEG (dry application) reduced thrombogenicity
      significantly (in heparinized animals) and thus appears to be promising for
      improving graft patency of small synthetic vascular prostheses.

PMID- 16288438
TI  - Soft tissue response to a new austenitic stainless steel with a negligible nickel
      content.
AB  - This study evaluates the soft tissue response to a new austenitic stainless steel
      with a low nickel content (P558) in comparison with a conventional stainless
      steel (SSt)and a titanium alloy (Ti6Al4V). Previous findings showed its in vitro
      biocompatibility by culturing P558 with healthy and osteoporotic osteoblasts and
      its in vivo effectiveness as bone implant material. Regarding its use as a
      material in osteosynthesis,P558 biocompatibility when implanted in soft tissues,
      as subcutis and muscle, was assessed. Disks and rods of these metals were
      implanted in rat subcutis and in rabbit muscle, respectively. Four and twelve
      weeks post surgery implants with surrounding tissue were retrieved for histologic
      and histomorphometric analysis: fibrous capsule thickness and new vessel
      formation were measured. Around all implanted materials, light microscopy
      highlighted a reactive and fibrous capsule formation coupled with ongoing
      neoangiogenesis both in rats and in rabbits. Histomorphometric measurements
      revealed a stronger inflammatory response,in terms of capsule
      thickness,surrounding SSt implants (9.8% Ni content) both in rat subcutis and in
      rabbit muscle independently of shape and site of implantation. A progressive
      decrease in capsule thickness around P558 (<0.02% Ni content) and Ti6Al4V,
      respectively, was seen. Regarding new vessel density, the data showed a different
      response dependent on the site of implantation. However,in the light of the
      previous and present studies, P558 is a good material, instead of titanium
      alloys, in orthopedic research.

PMID- 16288439
TI  - Rheotherapy for vascular disorders.
AB  - Patients with vascular disorders are seldom offered apheresis in he management of
      their symptoms. In this article we review the different apheretical techniques
      used in these situations.

PMID- 16288440
TI  - Hypertriglyceridemia: apheretic treatment.
AB  - Patients with extremely high triglyceride levels and associated lipemia are at
      high risk for acute pancreatitis. Two factors can increase triglyceride-rich
      lipoproteins; one is overproduction and other is a defect in clearance. Either
      mechanism can cause hypertriglyceridemia and both may exist simultaneously.
      Causes can be either primary or secondary. Plasmapheresis is efficacious for
      severe Hypertriglyceridemia in patients who have not responded to previous
      therapies. We have treated 15 cases of hypertriglyceridemia complicating the
      course of patients receiving Cyclosporin A after bone marrow transplantation.
      Five patients were treated with plasmapheresis, the other ten with cascade
      filtration. The removal rate for triglycerides was 58.0% for patients treated by
      cascade filtration and 63.5% for patients treated by plasmapheresis. The removal
      rates for triglycerides were low possibly as a consequence of early saturation of
      the filter.

PMID- 16288441
TI  - Hypercholesterolemia and LDL apheresis.
AB  - Several trials have assessed the link between low-density lipoprotein cholesterol
      (LDL) and the development of coronary heart disease (CHD). LDL apheresis provides
      an effective role in treating patients with familial hypercholesterolemia (FH)
      and in preventing the progression of coronary artery disease (CAD). Five
      different techniques of LDL apheresis are in current use: immunoadsorption (IMA),
      dextran sulphate-cellulose adsorption (DSA), heparin extracorporeal LDL
      precipitation system (HELP), double filtration plasmapheresis (DFPP) or
      lipidfiltration and direct adsorption of lipoprotein using hemoperfusion (DALI).
      All methods are efficient,but their cost restricts LDL apheresis to the treatment
      of FH. Indications could include other diseases, but controlled trials are still
      lacking.

PMID- 16288442
TI  - Hyperviscosity syndrome in hematological diseases and therapeutic apheresis.
AB  - The hyperviscosity syndrome classified into pleiocytosic, sclerotic and sieric
      syndromes according to the blood components involved are characterized by a
      different degree of clinical signs and symptoms related to rheological
      modification of blood. Therapeutic management of these syndromes is complex and
      the choice of apheresis treatment is generally restricted to emergency episodes
      in order to overcome the acute phase and to reverse the symptoms until definitive
      therapy is effective.

PMID- 16288443
TI  - Extracorporeal blood oxygenation and ozonation (EBOO): a controlled trial in
      patients with peripheral artery disease.
AB  - BACKGROUND: Since 1990 our group has been using extracorporeal circulation to
      ozonate blood by an original method, known as extracorporeal blood oxygenation
      and ozonation (EBOO), with the aim of amplifying the results observed with ozone
      autohemotherapy. OBJECTIVE: To verify the hypothesis that EBOO improves the skin
      lesions typical of peripheral artery disease (PAD) patients. METHODS: Twenty
      eight patients with PAD were randomized to receive EBOO or intravenous
      prostacyclin in a controlled clinical trial. The primary efficacy parameters were
      regression of skin lesions and pain,and improvement in quality of life and
      vascularisation. RESULTS: Patients treated with EBOO showed highly significant
      regression of skin lesions with respect to patients treated with prostacyclin.
      Other parameters that were significantly different in the two groups of patients
      were pain,pruritus, heavy legs and well-being. No significant differences in
      vascularisation of the lower limbs before and after treatment were found in
      either group. No side effects or complications were recorded during the 210 EBOO
      treatments. CONCLUSION: EBOO was much more effective than prostacyclin for
      treating skin lesions in PAD patients and also had a positive effect on patient
      general condition without any apparent change in arterial circulation. This
      suggests other mechanisms of action of EBOO.

PMID- 16288444
TI  - The origin of adaptive support ventilation.

PMID- 16288445
TI  - Fire hazards related to the use of dialysis machines.

PMID- 16288446
TI  - Comments on paper: "Hybrid test bench for evaluation of any device related to
      mechanical cardiac assistance".

PMID- 16288447
TI  - A randomized, controlled trial of mindfulness-based art therapy (MBAT) for women
      with cancer.
AB  - The purpose of this study was to gather data on the efficacy of a newly developed
      psychosocial group intervention for cancer patients, called mindfulness-based art
      therapy (MBAT). One hundred and eleven women with a variety of cancer diagnoses
      were paired by age and randomized to either an eight-week MBAT intervention group
      or a wait-list control group. Ninety-three participants (84%) completed both the
      pre- and post-study measurements. As compared to the control group, the MBAT
      group demonstrated a significant decrease in symptoms of distress (as measured by
      the Symptoms Checklist-90-Revised) and significant improvements in key aspects of
      health-related quality of life (as measured by the Medical Outcomes Study Short
      Form Health Survey). This investigation of MBAT provides initial encouraging data
      that support a possible future role for the intervention as a psychosocial
      treatment option for cancer patients.

PMID- 16288448
TI  - Dream content and psychological well-being: a longitudinal study of the
      continuity hypothesis.
AB  - This longitudinal study tested the continuity hypothesis, which postulates that
      waking states and concerns are reflected in dreams. The relationship between
      dream content and negative waking affect was investigated both at fixed points in
      time and over a 6- to 10-year period. Twenty-eight participants completed
      measures of psychological well-being (PWB) and kept a dream log at two periods of
      their lives. Correlational analyses showed that the lower the participants' self
      reported levels of PWB, the more their dreams tended to contain aggressive as
      opposed to friendly interactions, negative emotions as opposed to positive ones,
      and, to lesser extent, failures and misfortunes as opposed to successes and good
      fortunes. Similarly, PWB was significantly related to dream content over time.
      These findings are consistent with the continuity hypothesis.

PMID- 16288449
TI  - Limited validity of group additivity for the folding energetics of the peptide
      group.
AB  - The principle of group additivity is a standard feature of analyses of the
      energetics of protein folding, but it is known that it may not always be valid
      for the polar peptide group. The neighboring residue effect shows that group
      additivity is not strictly valid for a heteropeptide. We show here that group
      additivity fails seriously for peptide groups close to either peptide end, even
      for a homopeptide that has blocked end groups with no formal charges involved.
      The failure of group additivity is caused by the electrostatic character of the
      solvation of peptide polar groups and is illustrated with values of the
      electrostatic solvation free energy (ESF) calculated by DelPhi. Solvation free
      energies and enthalpies are known experimentally for monoamides and are often
      used to model the solvation of peptide groups, but ESF results show that
      monoamide values are very different from those of peptide groups. A main cause of
      the difference is that peptide solvation depends on the dipole-dipole
      interactions made between adjacent peptide groups, which vary with peptide
      conformation. Ligands that interact with the peptide backbone by an electrostatic
      mechanism could show a similar peptide end effect, and hydrogen exchange results
      from the literature confirm that exchange rates are position-dependent close to
      peptide ends.

PMID- 16288450
TI  - Causes and outcomes of pouch excision after restorative proctocolectomy.
AB  - BACKGROUND: Pouch failure occurs in up to 10 per cent of patients after ileal
      pouch-anal anastomosis (IPAA). The aims of this study were to determine the
      reasons for pouch excision and to evaluate the outcome of the perineal wound
      after pouch excision. METHODS: Between 1984 and 2002, 91 patients with severe
      ileal pouch dysfunction were treated. This was a retrospective analysis of data
      collected prospectively from 24 patients who underwent pouch excision. RESULTS:
      Patients were grouped according to the final histological diagnosis. Fourteen
      patients with Crohn's disease developed extensive fistulous disease and/or
      recurrent abscesses, of whom six had a persistent perineal sinus after pouch
      excision. Five patients had familial adenomatous polyposis, in three of whom
      desmoid tumours were the cause of failure. Three patients had chronic ulcerative
      colitis and developed recurrent pelvic sepsis. Finally, two patients with
      multiple colorectal adenocarcinoma developed recurrent cancer (one) or sepsis
      (one). CONCLUSION: Sepsis was the principal reason for pouch excision and was
      usually associated with recrudescent Crohn's disease in the pouch. Perineal wound
      healing was problematic after pouch excision for Crohn's disease.

PMID- 16288451
TI  - Evaluation of outcome of laparoscopic colorectal resection with POSSUM,
      Portsmouth POSSUM and colorectal POSSUM.
AB  - BACKGROUND: This study evaluated the Physiological and Operative Severity Score
      for the enUmeration of Mortality and morbidity (POSSUM), Portsmouth (P) POSSUM
      and colorectal (CR) POSSUM in laparoscopic colorectal resection. METHODS:
      Observed mortality and morbidity rates in 400 patients who underwent laparoscopic
      colorectal resection were compared with those predicted by POSSUM, P-POSSUM and
      CR-POSSUM. RESULTS: Observed mortality and morbidity rates were 0.5 and 19.0 per
      cent respectively. Mortality rates predicted by POSSUM, P-POSSUM and CR-POSSUM
      were 10.8, 4.0 and 5.6 per cent respectively, and the morbidity rate predicted by
      POSSUM was 43.0 per cent. The predicted and observed mortality and morbidity
      rates showed significant lack of fit. The conversion rate to open surgery was
      11.5 per cent. The mortality rate for patients having conversion was 2 per cent
      and was not significantly different to that predicted by P-POSSUM (4 per cent; P
      = 0.493) or CR-POSSUM (5 per cent; P = 0.370). In this group, the observed and
      POSSUM-predicted morbidity rates were also similar (43 versus 48 per cent
      respectively; P = 0.104). CONCLUSION: POSSUM, P-POSSUM and CR-POSSUM
      overestimated mortality and morbidity in patients who underwent laparoscopic
      colorectal resection. However, the mortality rate in patients who required
      conversion fitted the models of P-POSSUM and CR-POSSUM, and the morbidity rate
      was comparable to that predicted by POSSUM.

PMID- 16288452
TI  - Bacterial translocation studied in 927 patients over 13 years.
AB  - BACKGROUND: Bacterial translocation (BT) describes the passage of bacteria from
      the gastrointestinal tract to normally sterile tissues such as the mesenteric
      lymph nodes (MLNs) and other internal organs. The clinical and pathophysiological
      significance of BT remains controversial. This report describes results obtained
      over a 13-year period of study. METHODS: MLNs were obtained from 927 patients
      undergoing laparotomy. Nasogastric aspirates were obtained from 458 (49.4 per
      cent) of 927 patients for culture; pH was measured in 172 (37.6 per cent) of 458.
      Preoperative clinical variables were evaluated and factors that influenced BT
      were included in a multivariate logistic regression analysis. RESULTS: BT was
      identified in 130 (14.0 per cent) of 927 patients. Postoperative sepsis was more
      common in patients with BT (42.3 versus 19.9 per cent; P < 0.001). Independent
      preoperative variables associated with BT were emergency surgery (P = 0.001) and
      total parenteral nutrition (TPN) (P = 0.015). Gastric colonization was confirmed
      in 248 (54.1 per cent) of 458 patients, and was associated with both BT (P =
      0.015) and postoperative sepsis (P = 0.029). A gastric pH of less than 4 was
      associated with a significant reduction in gastric colonization (53 versus 80 per
      cent; P < 0.001) and postoperative sepsis (46 versus 70.3 per cent; P = 0.018)
      but not BT. CONCLUSION: BT is associated with postoperative sepsis. Emergency
      surgery and TPN are independently associated with an increased prevalence of BT.

PMID- 16288453
TI  - The CDR1 of the human lambdaVI light chains adopts a new canonical structure.
AB  - We performed a comparative analysis of the conformation of the CDR1 of the human
      lambdaVI variable domains JTO and WIL and the equivalent loop of the lambdaI
      light chains RHE and KOL, which are representative of the type I canonical
      structure for lambda light chains. On the basis of the differences found in the
      main chain conformation, as well as the identity of the residues at key
      positions, we showed that the L1 of some lambdaVI light chains adopts a
      conformation that represents a new type of canonical structure. The conformation
      of the L1 of those lambdaVI light chains, is primarily determined by the presence
      of an Arg residue at position 25. The analysis of the lambdaVI light chain
      sequences so far reported, showed that near 25% of those proteins have Gly at
      position 25 instead of Arg, which represents an allotypic variant of the lambdaVI
      variable locus. The presence of Gly at position 25 in the L1 of lambdaVI light
      chains would imply a different conformation for this loop. Additionally, the
      position 68 in lambdaVI light chains, which is at the top of the FR3 loop, showed
      such spatial orientation and variability that suggested its participation in the
      conformation of the antigen recognition surface in this subgroup of lambda
      chains.

PMID- 16288454
TI  - Molecular dynamics study on the folding and metallation of the individual domains
      of metallothionein.
AB  - De novo synthesis of metallothionein (MT) initially forms the metal-free protein,
      which must, in a posttranslational reaction, coordinate metal ions via the
      cysteine sulfur ligands to form the fully folded protein structure. In this
      article, we use molecular dynamics (MD) and molecular mechanics (MM) to
      investigate the metal-dependent folding steps of the individual domains of
      recombinant human metallothionein (MT). The divalent metals were removed
      sequentially from the metal-sulfur M4(Scys)11 and M3(Scys)9 clusters within the
      alpha- and beta- domains of MT, respectively, after protonation of the previously
      coordinating sulfurs. With each of the four (alpha) or three (beta) sites
      defined, an order of metal release could be determined on the basis of a
      comparison of the strain energies for each combination by selecting the lowest
      energy demetallated conformations. The effect of an additional noninteracting, 34
      residue peptide sequence on the demetallation order was assessed when bound to
      either the N- or C-termini of the individual domain fragments to identify the
      differences in cluster stability between one- and two-domain proteins. The N
      terminal-bound peptide had no effect on the order of metal removal; however,
      addition to the C-terminus significantly altered the sequence. The number of
      hydrogen bonds was calculated for each energy-minimized demetallated structure
      and was increased on metal removal, indicating a possible stabilization mechanism
      for the protein structure via a hydrogen-bonding network. On complete
      demetallation, the cysteinyl sulfurs were shown to move to the exterior surface
      of the peptide chain.

PMID- 16288455
TI  - Natively unfolded regions of the vertebrate fibrinogen molecule.
AB  - Although it has long been realized that a large portion of the fibrinogen alpha
      chain has little if any defined structure, the physiological significance of this
      flexible appendage remains mysterious.

PMID- 16288456
TI  - Structure and mechanism of the farnesyl diphosphate synthase from Trypanosoma
      cruzi: implications for drug design.
AB  - Typanosoma cruzi, the causative agent of Chagas disease, has recently been shown
      to be sensitive to the action of the bisphosphonates currently used in bone
      resorption therapy. These compounds target the mevalonate pathway by inhibiting
      farnesyl diphosphate synthase (farnesyl pyrophosphate synthase, FPPS), the enzyme
      that condenses the diphosphates of C5 alcohols (isopentenyl and dimethylallyl) to
      form C10 and C15 diphosphates (geranyl and farnesyl). The structures of the T.
      cruzi FPPS (TcFPPS) alone and in two complexes with substrates and inhibitors
      reveal that following binding of the two substrates and three Mg2+ ions, the
      enzyme undergoes a conformational change consisting of a hinge-like closure of
      the binding site. In this conformation, it would be possible for the enzyme to
      bind a bisphosphonate inhibitor that spans the sites usually occupied by
      dimethylallyl diphosphate (DMAPP) and the homoallyl moiety of isopentenyl
      diphosphate. This observation may lead to the design of new, more potent anti
      trypanosomal bisphosphonates, because existing FPPS inhibitors occupy only the
      DMAPP site. In addition, the structures provide an important mechanistic insight:
      after its formation, geranyl diphosphate can swing without leaving the enzyme,
      from the product site to the substrate site to participate in the synthesis of
      farnesyl diphosphate.

PMID- 16288457
TI  - Unique GMP-binding site in Mycobacterium tuberculosis guanosine monophosphate
      kinase.
AB  - Bacterial nucleoside monophosphate (NMP) kinases, which convert NMPs to
      nucleoside diphosphates (NDP), are investigated as potential antibacterial
      targets against pathogenic bacteria. Herein, we report the biochemical and
      structural characterization of GMP kinase from Mycobacterium tuberculosis
      (GMPKMt). GMPKMt is a monomer with an unusual specificity for ATP as a phosphate
      donor, a lower catalytic efficiency compared with eukaryotic GMPKs, and it
      carries two redox-sensitive cysteines in the central CORE domain. These
      properties were analyzed in the light of the high-resolution crystal structures
      of unbound, GMP-bound, and GDP-bound GMPKMt. The latter structure was obtained in
      both an oxidized form, in which the cysteines form a disulfide bridge, and a
      reduced form which is expected to correspond to the physiological enzyme. GMPKMt
      has a modular domain structure as most NMP kinases. However, it departs from
      eukaryotic GMPKs by the unusual conformation of its CORE domain, and by its
      partially open LID and GMP-binding domains which are the same in the apo-, GMP
      bound, and GDP-bound forms. GMPKMt also features a unique GMP binding site which
      is less close-packed than that of mammalian GMPKs, and in which the replacement
      of a critical tyrosine by a serine removes a catalytic interaction. In contrast,
      the specificity of GMPKMt for ATP may be a general feature of GMPKs because of an
      invariant structural motif that recognizes the adenine base. Altogether,
      differences in domain dynamics and GMP binding between GMPKMt and mammalian GMPKs
      should reveal clues for the design of GMPKMt-specific inhibitors.

PMID- 16288458
TI  - Search for autism loci by combined analysis of Autism Genetic Resource Exchange
      and Finnish families.
AB  - OBJECTIVE: Several genome-wide screens have been performed in autism spectrum
      disorders resulting in the identification of numerous putative susceptibility
      loci. Analyses of pooled primary data should result in an increased sample size
      and the different study samples have a potential to strengthen the evidence for
      some earlier identified loci, reveal novel loci, and even to provide information
      of the general significance of the locus. The objective of this study was to
      search for potential susceptibility loci for autism, which are supported by two
      independent samples. METHODS: We performed a combined analysis of the primary
      genome scan data of the Autism Genetic Resource Exchange (AGRE) and Finnish
      autism samples to reveal susceptibility loci potentially shared by these study
      samples. RESULTS: In the initial combined data analysis, the best loci (p < 0.05)
      were observed at 1p12-q25, 3p24-26, 4q21-31, 5p15-q12, 6q14-21, 7q33-36, 8q22-24,
      17p12-q21, and 19p13-q13. The combined analysis of Finnish and AGRE families
      showed the most promising shared locus on 3p24-26 with nonparametric logarithm of
      odds (NPL) score of 2.20 (p = 0.011). The combined data analysis did not provide
      increased linkage evidence for the earlier identified loci on 3q25-27 or 17p12
      q21. However, the 17p12-q21 locus remained promising also in the combined sample
      (NPL(all) =2.38, p = 0.0076). INTERPRETATION: Our study of 314 autism families
      highlights the importance of further analyses on 3p24-26 locus involving
      comprehensive molecular genetic analyses of oxytocin receptor gene (OXTR), a
      positional and functional candidate gene for autism.

PMID- 16288459
TI  - Regulation of the p53 transcriptional activity.
AB  - In response to various stresses, p53 is rapidly activated and transcriptionally
      regulates a number of target genes by which p53 modulates a variety of cellular
      activities. The transcriptional activity of p53 is delicately regulated by a
      plethora of cellular factors, independently or synergistically, in multiple ways
      in order to achieve a specific response. This article reviewed the role of the
      basal transcriptional machinery, co-activators, and co-repressors involved in p53
      dependent transcription, and the underlying mechanism by which the p53
      transcriptional activity is regulated. We also discussed some potentially
      interesting questions and future directions in the field.

PMID- 16288460
TI  - Signaling roles of diacylglycerol kinases.
AB  - Diacylglycerol kinases (DGKs) attenuate diacylglycerol signaling by converting
      this lipid to phosphatidic acid (PA). The nine mammalian DGKs that have been
      identified are widely expressed, but each isoform has a unique tissue and
      subcellular distribution. Their kinase activity is regulated by mechanisms that
      modify their access to diacylglycerol, directly affect their kinase activity, or
      alter their ability to bind to other proteins. In many cases, these enzymes
      regulate the activity of proteins that are modulated by either diacylglycerol or
      PA. Experiments using cultured cells and model organisms have demonstrated that
      DGKs have prominent roles in neuronal transmission, lymphocyte signaling, and
      carcinogenesis.

PMID- 16288461
TI  - Modeling disease in the mouse: lessons from DNA damage response and cell cycle
      control genes.
AB  - The advent of gene targeting has allowed the dissection of many essential
      cellular pathways, including those involved in cell cycle regulation, signal
      transduction, and development. However, it is becoming increasingly clear that
      the simple gene deletion strategy may not be sufficient for the modeling of many
      cancer syndromes. In this Prospect article, we will discuss the strengths and
      weaknesses of mouse models, how they have advanced from gene deletions to
      truncations, point mutations, and conditional mouse models in which expression or
      loss of the gene of interest is controlled either temporally or spatially. We
      will also consider future directions for the use of mouse models in cancer. The
      vastness of the field necessitates focusing on a few specific examples with the
      unfortunate exclusion of many excellent studies from our discussion. As such, we
      focus on a few specific models of human cancer syndromes, however many of the
      themes discussed here are applicable to other systems of genetic manipulation and
      may be applied across fields.

PMID- 16288462
TI  - Dynamics of the trimeric AcrB transporter protein inferred from a B-factor
      analysis of the crystal structure.
AB  - The Escherichia coli AcrB multidrug transporter recognizes a wide range of toxic
      chemicals and actively extrudes them from cells. The molecular basis of multidrug
      transport in AcrB remains unknown. Herein, we describe normal mode analyses to
      study important regions for drug recognition and extrusion in this transporter.
      Based on the X-ray structure of AcrB, an elastic network model has been able to
      correct errors arising from crystal imperfection in the experimental B-factors.
      The results allow us to understand the functional dynamics of this membrane
      protein. It is expected that this technique can be applied to other membrane
      proteins with known structures.

PMID- 16288463
TI  - Generation and characterization of brain lipid-binding protein promoter-based
      transgenic mouse models for the study of radial glia.
AB  - Radial glia play an essential role in the generation of the cerebral cortex
      through their function as neuronal precursors and as neuronal migration guides. A
      molecular marker for radial glia in the developing central nervous system is the
      brain lipid-binding protein (BLBP). To generate mouse models for the
      visualization and study of radial glia, we expressed EGFP, EYFP, or dsRed2 in
      transgenic mice under the control of the BLBP promoter. In these transgenic
      lines, fluorescent protein expression is restricted to radial glia in the
      embryonic cortex and to astrocytes in the adult brain. Electroporation of the
      transgenes into embryonic cortex also resulted in radial glia-specific transgene
      expression. These BLBP promoter driven transgenic mice and organotypic brain
      slices expressing different fluorescent markers in a radial glia-specific manner
      will be useful tools to further study the differentiation and function of radial
      glia in distinct regions of the developing CNS.

PMID- 16288464
TI  - Protection of corticospinal tract neurons after dorsal spinal cord transection
      and engraftment of olfactory ensheathing cells.
AB  - Transplantation of olfactory ensheathing cells (OECs) into the damaged rat spinal
      cord leads to directed elongative axonal regeneration and improved functional
      outcome. OECs are known to produce a number of neurotrophic molecules. To explore
      the possibility that OECs are neuroprotective for injured corticospinal tract
      (CST) neurons, we transplanted OECs into the dorsal transected spinal cord (T9)
      and examined primary motor cortex (M1) to assess apoptosis and neuronal loss at 1
      and 4 weeks post-transplantation. The number of apoptotic cortical neurons was
      reduced at 1 week, and the extent of neuronal loss was reduced at 4 weeks.
      Biochemical analysis indicated an increase in BDNF levels in the spinal cord
      injury zone after OEC transplantation at 1 week. The transplanted OECs associated
      longitudinally with axons at 4 weeks. Thus, OEC transplantation into the injured
      spinal cord has distant neuroprotective effects on descending cortical projection
      neurons.

PMID- 16288465
TI  - Epo protects SOD2-deficient mouse astrocytes from damage by oxidative stress.
AB  - Erythropoietin (Epo) expression, which regulates erythropoiesis, has been shown
      in rat and mouse brain after hypoxia. A previous study from our laboratory showed
      that astrocytes from manganese-superoxide dismutase (SOD2) homozygous knockout
      (SOD2(-/-)) mice can survive under 5% O(2), but not under normal aerobic
      conditions. However, the mechanism involved is not clear. Our preliminary study
      using reverse transcriptase-polymerase chain reaction showed increased Epo mRNA
      expression in astrocytes cultured with 5% hypoxia compared with astrocytes under
      normal conditions. After administration of anti-sense Epo, protection decreased
      with time. Dose-dependent administration of Epo to SOD2(-/-) mouse astrocytes
      improved their survivability under normal conditions. Survivability of
      heterozygous SOD2(-/+) mutant and wild-type mouse astrocyte cultures was the same
      under normal conditions but, after administration of 2 mM of paraquat, a reactive
      oxygen species generator, survivability of the SOD2(-/+) astrocytes decreased
      remarkably compared with the wild-type cells. Epo administration 24 h before
      exposure to paraquat significantly improved the survivability of the SOD2(-/+)
      astrocytes. Western blot studies suggest that Jak-Stat signal transduction
      pathways are involved in this process. Our study demonstrates an important role
      for Epo in the protection of astrocytes from reactive oxygen species. We suggest
      that Epo can compensate in part for the antioxidant properties of mitochondrial
      SOD2 deficiency.

PMID- 16288466
TI  - Membrane currents elicited by angiotensin II in astrocytes from the rat corpus
      callosum.
AB  - The corpus callosum (CC) is the main white matter tract in the brain. It consists
      primarily of axons and glial cells. In the present work, membrane currents
      generated by angiotensin II (Ang II) in cultured astrocytes from the CC of
      newborn and 3-week-old rats were studied using the whole-cell voltage-clamp
      technique. After 4 days of culture, approximately 90% of cells were positive to
      glial fibrillary acidic protein (GFAP), indicating their astrocyte lineage. Ang
      II elicited inward currents in approximately 20% of cells and outward currents in
      approximately 4% of cells from the CC for newborn or 3-week-old rats. The main
      effect of Ang II on astrocytes from the newborn rat CC was a reduction of
      membrane conductance, by blocking of delayed rectifier K(+) currents in 96% of
      cells. However, no common action of Ang II was observed in cells from 3-week-old
      rat CC because the responses were quite variable, suggesting the participation of
      other ion currents. The partial agonist of AT(2) receptors, CGP-42112A, exerted
      effects on Ang II responses, whereas the AT(1) antagonist ZD7155 did not,
      suggesting that Ang II responses in CC astrocytes are predominantly mediated by
      activation of AT(2) receptors. This study is the first to show electrical
      responses generated by AT(2) receptors in glial cells from the rat central
      nervous system, and may help gain a better understanding of the functions of Ang
      II receptors in astrocytes from the rat CC in particular and of glial cells in
      general. (c) 2005 Wiley-Liss, Inc.

PMID- 16288467
TI  - Sulfatide is essential for the maintenance of CNS myelin and axon structure.
AB  - Galactocerebroside (GalC) and sulfatide are abundant myelin lipids. In mice
      incapable of synthesizing these lipids, myelin is thin and regionally unstable
      and exhibits several subtle structural abnormalities. Although galactolipid-null
      mice have been beneficial in the analysis of galactolipid function, it has not
      been possible to differentiate between the functions of GalC and sulfatide with
      these mice alone. In the present work, we have analyzed a murine model that forms
      normal levels of GalC but is incapable of synthesizing sulfatide. By comparing a
      plethora of morphological features between the galactolipid-null and the
      sulfatide-null mice, we have begun to differentiate between the specific
      functions of these closely related lipids. The most striking difference between
      these two mutants is the reduction of myelin developmental abnormalities (e.g.,
      redundant and uncompacted myelin sheaths) in young adult sulfatide-null mice as
      compared with the galactolipid-null animals. Although sulfatide appears to play a
      limited role in myelin development, this lipid is essential for myelin
      maintenance, as the prevalence of redundant, uncompacted, and degenerating myelin
      sheaths as well as deteriorating nodal/paranodal structure is increased
      significantly in aged sulfatide-null mice as compared with littermate wildtype
      mice. Finally, we show that the role played by sulfatide in CNS maintenance is
      not limited to the myelin sheath, as axonal caliber and circularity are normal in
      young adult mutant mice but are significantly altered in aged sulfatide-null
      animals.

PMID- 16288470
TI  - Expression profile of IGF system during lung injury and recovery in rats exposed
      to hyperoxia: a possible role of IGF-1 in alveolar epithelial cell proliferation
      and differentiation.
AB  - Although several studies have shown that an induction of insulin-like growth
      factor (IGF) components occurs during hyperoxia-mediated lung injury, the role of
      these components in tissue repair is not well known. The present study aimed to
      elucidate the role of IGF system components in normal tissue remodeling. We used
      a rat model of lung injury and remodeling by exposing rats to > 95% oxygen for 48
      h and allowing them to recover in room air for up to 7 days. The mRNA expression
      of IGF-I, IGF-II, and IGF-1 receptor (IGF-1R) increased during injury. However,
      the protein levels of these components remained elevated until day 3 of the
      recovery and were highly abundant in alveolar type II cells. Among IGF binding
      proteins (IGFBPs), IGFBP-5 mRNA expression increased during injury and at all the
      recovery time points. IGFBP-2 and -3 mRNA were also elevated during injury phase.
      In an in vitro model of cell differentiation, the expression of IGF-I and IGF-II
      increased during trans-differentiation of alveolar epithelial type II cells into
      type-I like cells. The addition of anti-IGF-1R and anti-IGF-I antibodies
      inhibited the cell proliferation and trans-differentiation to some extent, as
      evident by cell morphology and the expression of type I and type II cell markers.
      These findings demonstrate that the IGF signaling pathway plays a critical role
      in proliferation and differentiation of alveolar epithelium during tissue
      remodeling.

PMID- 16288471
TI  - Transcriptional regulation of VCAM-1 expression by tumor necrosis factor-alpha in
      human tracheal smooth muscle cells: involvement of MAPKs, NF-kappaB, p300, and
      histone acetylation.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been shown to induce the expression
      of adhesion molecules in airway resident cells and contribute to inflammatory
      responses. Here, the roles of mitogen-activated protein kinases (MAPKs) and NF
      kappaB in TNF-alpha-induced expression of vascular cell adhesion molecule (VCAM)
      1 were investigated in human tracheal smooth muscle cells (HTSMCs). TNF-alpha
      enhanced expression of VCAM-1 protein and mRNA as well as phosphorylation of
      p42/p44 MAPK, p38, and JNK were significantly attenuated by inhibitors of MEK1/2
      (U0126), p38 (SB202190), and JNK (SP600125). Transfection with dominant negative
      mutants of MEK1/2, ERK1, ERK2, p38, and JNK attenuated TNF-alpha-induced VCAM-1
      expression. Furthermore, TNF-alpha-induced VCAM-1 expression was significantly
      blocked by a selective NF-kappaB inhibitor helenalin. TNF-alpha-stimulated
      translocation of NF-kappaB into the nucleus and degradation of IkappaB-alpha was
      blocked by helenalin, but not by U0126, SB202190, or SP600125. VCAM-1 promoter
      activity was enhanced by TNF-alpha in HTSMCs transfected with VCAM-1-Luc, which
      was inhibited by helenalin, U0126, SB202190, and SP600125. Most surprisingly,
      VCAM-1 expression was also significantly blocked by a selective inhibitor of
      p300, curcumin. NF-kappaB transcription factor and p300 were associated with the
      VCAM-1 promoter, which was dynamically linked to histone H3 acetylation
      stimulated by TNF-alpha, as determined by chromatin immunoprecipitation assay.
      Moreover, the resultant enhancement of VCAM-1 expression increased the adhesion
      of polymorphonuclear cells (PMNs) to monolayer of HTSMCs, which was blocked by
      helenalin, U0126, SB202190, or SP600125. These results suggest that in HTSMCs,
      activation of MAPK pathways, NF-kappaB, and p300 is essential for TNF-alpha
      induced VCAM-1 expression.

PMID- 16288472
TI  - Heparanase mechanisms of melanoma metastasis to the brain: Development and use of
      a brain slice model.
AB  - Heparanase (HPSE-1) is an endo-beta-D-glucuronidase that cleaves heparan sulfate
      (HS) chains of proteoglycans (HSPG), and its expression has been associated with
      increased cell growth, invasion, and angiogenesis of tumors as well as with
      embryogenesis and tissue development. Since metastatic cancer cells express HPSE
      1, we have developed an orthotopic brain slice model to study HPSE-1 involvement
      in brain-metastatic melanoma. This model allows for the characterization of tumor
      cell invasion at both quantitative and qualitative levels. Brain-metastatic
      melanoma cells (B16B15b) showed augmenting levels of HPSE-1 protein expression in
      a time-dependent manner. Secondly, B16B15b cells pre-treated with HPSE-1 showed a
      significant increase in the number of cells that invaded into the brain tissue.
      Finally, HPSE-1 exposure-augmented invasion depth in brain sections by brain
      metastatic melanoma cells. We concluded that applying this brain slice model can
      be beneficial to investigate HPSE-1- related in vivo modalities in brain
      metastatic melanoma and brain invasion in general. These results also further
      emphasize the potential relevance of using this model to design therapies for
      controlling this type of cancer by blocking HPSE-1 functionality.

PMID- 16288473
TI  - Binding and functional characteristics of two E-box motifs within the S100A6
      (calcyclin) gene promoter.
AB  - S100A6 (calcyclin) is a small calcium-binding protein of the S100 family often
      associated with cancer and metastasis. We have previously shown that the E-box
      sequence at position -283/-278 of the S100A6 gene promoter interacts with USF
      transcription factor and contributes to promoter transcriptional activity. We now
      present evidence that a second E-box motif at position -593/-588 of the promoter
      also binds USF and that the USF1/USF2 heterodimer is the prevailing dimeric form
      of the transcription factor bound. Using the chromatin immunoprecipitation assay
      (ChIP), we show that USF is bound in vivo to the E-box regulatory element(s).
      Depletion of the endogenous USF pool by means of a decoy oligonucleotide evokes a
      severe inhibition of S100A6 gene promoter activity. Furthermore, we show that
      S100A6 gene promoter activity can be stimulated by palmitate and that mutation of
      the -283/-278 E-box sequence completely blocks this stimulation.

PMID- 16288474
TI  - Cell proliferation in the Rana catesbeiana auditory medulla over metamorphic
      development.
AB  - During metamorphic development, bullfrogs (Rana catesbeiana) undergo substantial
      morphological, anatomical, and physiological changes as the animals prepare for
      the transition from a fully-aquatic to a semi-terrestrial existence. Using BrdU
      incorporation and immunohistochemistry, we quantify changes in cell proliferation
      in two key auditory brainstem nuclei, the dorsolateral nucleus and the superior
      olivary nucleus, over the course of larval and early postmetamorphic development.
      From hatchling through early larval stages, numbers of proliferating cells
      increase in both nuclei, paralleling the overall increase in total numbers of
      cells available for labeling. Numbers of proliferating cells in the superior
      olivary nucleus decrease during the late larval and deaf periods, and
      significantly increase during metamorphic climax. Proliferating cells in the
      dorsolateral nucleus increase in number from hatchling to late larval stages,
      decrease during the deaf period, and increase during climax. In both nuclei,
      numbers of proliferating cells decrease during the postmetamorphic froglet stage,
      despite increases in the number of cells available for label. Newly generated
      cells express either glial- or neural-specific phenotypes beginning between 1
      week and 1 month post-BrdU injection, respectively, while some new cells express
      gamma-aminobutyric acid within 2 days of mitosis. Our data show that these
      auditory nuclei dramatically up-regulate mitosis immediately prior to
      establishment of a transduction system based on atmospheric hearing.

PMID- 16288475
TI  - Novel kruppel-like factor is induced by neuronal activity and by sensory input in
      the central nervous system of the terrestrial slug Limax valentianus.
AB  - In the Limax central nervous system, the procerebrum is thought to be the locus
      of odor information processing and odor memory retention, but little is known
      about the input pathway of the noxious stimuli used in this learning protocol. To
      gain insight into the sensory information processing of the noxious stimuli
      involved in memory formation, we screened genes induced by artificial neuronal
      activity, and identified one kruppel-like factor (KLF) family transcription
      factor gene (Limax KLF; limKLF), which is up-regulated 30 min after
      depolarization. The limKLF protein fused to GFP was localized to the nucleus in
      COS-7 cells. We also cloned an immediate early gene, CCAAT enhancer binding
      protein (C/EBP), of Limax by reverse transcription-polymerase chain reaction (RT
      PCR). Both genes were up-regulated by dissection of the central nervous system
      (CNS) out of the slug in a protein synthesis-independent manner, and also by
      various noxious stimuli to the slug's body. These genes may be useful as neuronal
      activity markers in Limax to visualize activated sensory nervous systems.

PMID- 16288476
TI  - Calbindin-positive neurons reveal a sexual dimorphism within the songbird
      analogue of the mammalian auditory cortex.
AB  - The oscine song system, a set of interconnected brain nuclei involved in song
      production and learning, is one of the first and clearest examples of brain
      sexual dimorphism in a vertebrate, being typically well-developed in males, but
      not females. Here we present evidence for a sexual dimorphism in the caudomedial
      nidopallidum (NCM), an auditory area outside of the song system. NCM is thought
      to correspond to a portion of the auditory cortex of mammals and is involved in
      the perceptual processing of birdsong. We show that cells immunolabeled for the
      calcium-binding protein calbindin are primarily localized to caudal NCM and are
      almost twice as numerous in males as in females. We demonstrate that calbindin
      positive cells constitute a subset of GABAergic cells in NCM, and show that the
      sex dimorphism in this cell population does not result from local gender
      differences in the overall density of neuronal or GABAergic cells. In addition,
      we demonstrate that calbindin-positive cells lack song-induced expression of the
      activity-dependent gene ZENK, and that song stimulation does not change the
      density or distribution of these cells in NCM. Finally, we show that the
      distribution of calbindin-positive cells in NCM is strikingly similar to the mRNA
      expression for the estrogen-generating enzyme aromatase. Together these results
      suggest that NCM is likely composed of neurochemically-distinct domains and
      presents a marked sex dimorphism in a specific subset of GABAergic neurons, which
      may confer sex-specific sensory processing capabilities to this auditory area.
      Our results also suggest that local sex steroid hormones may play a local role in
      auditory processing in the songbird telencephalon.

PMID- 16288477
TI  - PLP1 alternative splicing in differentiating oligodendrocytes: characterization
      of an exonic splicing enhancer.
AB  - Proteolipid protein (PLP) and DM20 are generated by alternative splicing of exon
      3B of PLP1 transcript in differentiating oligodendrocytes. We investigated the
      role of exonic splicing enhancers (ESE) in the selection of PLP 5' donor site,
      focusing on putative ASF/SF2, and SC35 binding motifs in exon 3B on the basis of
      mutations that cause disease in humans. Mutations in a putative ASF/SF2 binding
      motif (nucleotides 406-412) reduced PLP 5' donor site selection, whereas a
      mutation in a putative SC35 binding motif (nucleotides 382-389) had no effect. UV
      crosslinking and immunoprecipitation (IP) assays using an antibody to ASF/SF2
      showed that the ASF/SF2 protein specifically binds to the ESE (nucleotides 406
      412). The single nucleotide mutations that reduced PLP splice site selection
      greatly diminished ASF/SF2 protein binding to this motif. We next tested the
      effect of overexpressed ASF/SF2 on PLP 5'splice selection in differentiating
      oligodendrocytes. ASF/SF2 positively regulates PLP splice site selection in a
      concentration-dependent manner. Disruption of the putative ASF/SF2 binding site
      in exon 3B reduced the positive effect of ASF/SF2 on PLP splicing. We conclude
      that an ESE in exon3B regulates PLP 5' donor site selection and that ASF/SF2
      protein participates in the regulation of PLP alternative splicing in
      oligodendrocytes.

PMID- 16288478
TI  - Ascorbate depletion mediates up-regulation of hypoxia-associated proteins by cell
      density and nickel.
AB  - Exposure of human lung cells to carcinogenic nickel compounds in the presence of
      oxygen up-regulated carbonic anhydrase IX (CA IX) and NDRG1/Cap43, both known as
      intrinsic hypoxia markers and cancer-associated genes. This suggests that factors
      other than a shortage of oxygen may be involved in this induction. Both proteins
      can also be induced in the presence of oxygen by culturing these cells to a high
      density without medium change. The intracellular ascorbate measurements revealed
      its rapid depletion in both metal- and density-exposed cells. Nickel exposure
      caused strong activation of HIF-1alpha and HIF-2alpha proteins, underscoring
      activation of HIF-1-dependent transcription. In contrast, cell density-dependent
      transcription was characterized by minor induction of HIF-1alpha or HIF-2alpha.
      Moreover, the up-regulation of NDRG1/Cap43 in HIF-1alpha deficient fibroblasts
      suggested the involvement of different transcription factor(s). The repletion of
      intracellular ascorbate reversed the induction of CA IX and NDRG1/Cap43 caused by
      cell density or nickel exposure. Thus, the loss of intracellular ascorbate
      triggered the induction of both tumor markers by two different conditions in the
      presence of oxygen. Ascorbate is delivered to lung cells via the SVCT2 ascorbate
      transporter, which was found to be sensitive to nickel or cell density.
      Collectively these findings establish the importance of intracellular ascorbate
      levels for the regulation of expression of CA IX and NDRG1/Cap43. We suggest,
      that, in addition to low oxygenation, insufficient supply of ascorbate or its
      excessive oxidation in tumors, can contribute to the induction of hypoxia
      associated proteins via both HIF-dependent and independent mechanisms.

PMID- 16288479
TI  - Mechanical forces alter zyxin unbinding kinetics within focal adhesions of living
      cells.
AB  - The formation of focal adhesions that mediate alterations of cell shape and
      movement is controlled by a mechanochemical mechanism in which cytoskeletal
      tensional forces drive changes in molecular assembly; however, little is known
      about the molecular biophysical basis of this response. Here, we describe a
      method to measure the unbinding rate constant k(OFF) of individual GFP-labeled
      focal adhesion molecules in living cells by modifying the fluorescence recovery
      after photobleaching (FRAP) technique and combining it with mathematical
      modeling. Using this method, we show that decreasing cellular traction forces on
      focal adhesions by three different techniques--chemical inhibition of
      cytoskeletal tension generation, laser incision of an associated actin stress
      fiber, or use of compliant extracellular matrices--increases the k(OFF) of the
      focal adhesion protein zyxin. In contrast, the k(OFF) of another adhesion
      protein, vinculin, remains unchanged after tension dissipation. Mathematical
      models also demonstrate that these force-dependent increases in zyxin's k(OFF)
      that occur over seconds are sufficient to quantitatively predict large-scale
      focal adhesion disassembly that occurs physiologically over many minutes. These
      findings demonstrate that the molecular binding kinetics of some, but not all,
      focal adhesion proteins are sensitive to mechanical force, and suggest that force
      dependent changes in this biophysical parameter may govern the supramolecular
      events that underlie focal adhesion remodeling in living cells.

PMID- 16288480
TI  - Arboreal bipedalism in wild chimpanzees: implications for the evolution of
      hominid posture and locomotion.
AB  - Field observations of bipedal posture and locomotion in wild chimpanzees (Pan
      troglodytes) can serve as key evidence for reconstructing the likely origins of
      bipedalism in the last prehominid human ancestor. This paper reports on a sample
      of bipedal bouts, recorded ad libitum, in wild chimpanzees in Bwindi Impenetrable
      National Park in southwestern Uganda. The Ruhija community of chimpanzees in
      Bwindi displays a high rate of bipedal posture. In 246.7 hr of observation from
      2001-2003, 179 instances of bipedal posture lasting 5 sec or longer were
      recorded, for a rate of 0.73 bouts per observation hour. Bipedalism was observed
      only on arboreal substrates, and was almost all postural, and not locomotor.
      Bipedalism was part of a complex series of positional behaviors related to
      feeding, which included two-legged standing, one-legged standing with arm
      support, and other intermediate postures. Ninety-six percent of bipedal bouts
      occurred in a foraging context, always as a chimpanzee reached to pluck fruit
      from tree limbs. Bipedalism was seen in both male and female adults, less
      frequently among juveniles, and rarely in infants. Both the frequency and
      duration of bipedal bouts showed a significant positive correlation with
      estimated substrate diameter. Neither fruit size nor nearest-neighbor association
      patterns were significantly correlated with the occurrence of bipedalism.
      Bipedalism is seen frequently in the Bwindi chimpanzee community, in part because
      of the unusual observer conditions at Bwindi. Most observations of bipedalism
      were made when the animals were in treetops and the observer at eye-level across
      narrow ravines. This suggests that wild chimpanzees may engage in bipedal
      behavior more often than is generally appreciated. Models of the likely
      evolutionary origins of bipedalism are considered in the light of Bwindi
      bipedalism data. Bipedalism among Bwindi chimpanzees suggests the origin of
      bipedal posture in hominids to be related to foraging advantages in fruit trees.
      It suggests important arboreal advantages in upright posture. The origin of
      postural bipedalism may have preceded and been causally disconnected from
      locomotor bipedalism.

PMID- 16288481
TI  - Diverse microglial responses after intrahippocampal administration of
      lipopolysaccharide.
AB  - Inflammation has been argued to play a primary role in the pathogenesis of
      Alzheimer's disease by contributing to the development of neuropathology and
      clinical symptoms. However, the mechanisms underlying these effects remain
      obscure. Lipopolysaccharide (LPS) activates the innate immune response and
      triggers gliosis when injected into the central nervous system. In the studies
      described in the present work, we evaluated the time course of microgliosis after
      a single intrahippocampal injection of LPS. Mice were injected bilaterally with 4
      mug of LPS. Post-injection survival times were 1, 6, and 24 h, as well as 3, 7,
      14, and 28 days. Protein and RNA analyses were performed for inflammatory
      markers. Significant elevations of cluster differentiation marker CD45, glial
      fibrillary acidic protein (GFAP), scavenger receptor A (SRA), and Fcgamma
      receptor mRNA were seen after 24 h. Immunohistochemistry revealed a complex
      pattern of protein expression by microglia, as well as changes in cell
      morphologies. RNA and protein for Fcgamma receptor and SRA were transiently
      elevated, peaked at 3 days, and returned to basal levels after 1 week. In
      contrast, microglia remained significantly activated through the 28-day time
      point, as determined by CD45 and complement receptor 3 levels. These findings
      indicate a multivariate response to LPS, and evaluation of microglial phenotypes
      may lead to a better understanding of neuroinflammatory diseases.

PMID- 16288482
TI  - Modeling evolution of hydrogen bonding and stabilization of transition states in
      the process of cocaine hydrolysis catalyzed by human butyrylcholinesterase.
AB  - Molecular dynamics (MD) simulations and quantum mechanical/molecular mechanical
      (QM/MM) calculations were performed on the prereactive enzyme-substrate complex,
      transition states, intermediates, and product involved in the process of human
      butyrylcholinesterase (BChE)-catalyzed hydrolysis of (-)-cocaine. The
      computational results consistently reveal a unique role of the oxyanion hole
      (consisting of G116, G117, and A199) in BChE-catalyzed hydrolysis of cocaine,
      compared to acetylcholinesterase (AChE)-catalyzed hydrolysis of acetylcholine.
      During BChE-catalyzed hydrolysis of cocaine, only G117 has a hydrogen bond with
      the carbonyl oxygen (O31) of the cocaine benzoyl ester in the prereactive BChE
      cocaine complex, and the NH groups of G117 and A199 are hydrogen-bonded with O31
      of cocaine in all of the transition states and intermediates. Surprisingly, the
      NH hydrogen of G116 forms an unexpected hydrogen bond with the carboxyl group of
      E197 side chain and, therefore, is not available to form a hydrogen bond with O31
      of cocaine in the acylation. The NH hydrogen of G116 is only partially available
      to form a weak hydrogen bond with O31 of cocaine in some structures involved in
      the deacylation. The change of the estimated hydrogen-bonding energy between the
      oxyanion hole and O31 of cocaine during the reaction process demonstrates how the
      protein environment can affect the energy barrier for each step of the BChE
      catalyzed hydrolysis of cocaine. These insights concerning the effects of the
      oxyanion hole on the energy barriers provide valuable clues on how to rationally
      design BChE mutants with a higher catalytic activity for the hydrolysis of (-)
      cocaine.

PMID- 16288483
TI  - Diagnosis and treatment of intestinal malabsorption in cystic fibrosis.
AB  - Intestinal malabsorption is severe and of early onset in virtually all people who
      have cystic fibrosis. The main cause is deficiency of pancreatic enzymes.
      Bicarbonate deficiency, abnormal bile salts, mucosal transport problems, motility
      differences, and anatomical structural changes are other contributory factors.
      Effective treatment should allow a normal to high-fat diet to be taken, control
      symptoms, correct malabsorption, and achieve a normal nutritional state and
      growth. Appropriate pancreatic enzyme replacement therapy will achieve normal or
      near-normal absorption in most people with cystic fibrosis. Early identification
      and treatment of intestinal malabsorption is critical to achieving optimal
      nutritional status. The occurrence of fibrosing colonopathy in a few patients on
      very high doses of those enzymes which have the copolymer Eudragit L30 D55 in
      their covering resulted in guidelines in the UK to avoid doses equivalent to more
      than 10,000 IU lipase per kg per day, and also to avoid preparations containing
      this copolymer in children and adolescents. For patients not responding to 10,000
      IU lipase per kg per day review of adherence to treatment, change of enzyme
      preparation, variation in time of administration, and reduction in gastric acid
      may improve absorption. The importance of early investigation to exclude other
      gastrointestinal disorders as a cause of the patient's symptoms, rather than
      merely increasing the dose of enzymes, is stressed. With modern pancreatic
      enzymes in doses up to or only slightly in excess of 10,000 IU lipase per kg per
      day, adequate control of gastrointestinal symptoms and absorption can be
      achieved, and a normal nutritional state and growth rate maintained in most
      people with cystic fibrosis.

PMID- 16288484
TI  - Lung function tests in neonates and infants with chronic lung disease: forced
      expiratory maneuvers.
AB  - This fourth paper in a review series on the role of lung function testing in
      infants and young children with acute neonatal disorders and chronic lung disease
      of infancy (CLDI) addresses measurements of forced expiration using rapid thoraco
      abdominal compression (RTC) techniques and the forced deflation technique.
      Following orientation of the reader to the subject area, we focus our comments on
      the areas of inquiry proposed in the introductory paper to this series. The
      quality of the published literature is reviewed critically, and recommendations
      are provided to guide future investigation in this field. All studies on infants
      and young children with CLDI using forced expiratory or deflation maneuvers
      demonstrated that forced flows at low lung volume remain persistently low through
      the first 3 years of life. Measurement of maximal flow at functional residual
      capacity (V'maxFRC) is the most commonly used method for assessing airway
      function in infants, but is highly dependent on lung volume and airway tone.
      Recent studies suggested that the raised volume RTC technique, which assesses
      lung function over an extended volume range as in older children, may be a more
      sensitive means of discriminating changes in airway function in infants with
      respiratory disease. The forced deflation technique allows investigation of
      pulmonary function during the early development of CLDI in intubated subjects,
      but its invasive nature precludes its use in the routine setting. For all
      techniques, there is an urgent need to establish suitable reference data and
      evaluate within- and between-occasion repeatability, prior to establishing the
      clinical usefulness of these techniques in assessing baseline airway function
      and/or response to interventions in subjects with CLDI.

PMID- 16288485
TI  - Elderly subgroup analysis of a randomized phase III study of docetaxel plus
      platinum combinations versus vinorelbine plus cisplatin for first-line treatment
      of advanced nonsmall cell lung carcinoma (TAX 326).
AB  - BACKGROUND: Controversy continues over whether elderly patients with advanced
      nonsmall cell lung carcinoma (NSCLC) should receive platinum-based chemotherapy.
      TAX 326 reported improved survival with docetaxel-cisplatin (DC) versus
      vinorelbine-cisplatin (VC) for advanced NSCLC. DC and docetaxel-carboplatin (DCb)
      were better tolerated than VC. We analyzed the efficacy and toxicity in patients
      ages < 65 and > or = 65 years. METHODS: Chemotherapy-naive, TNM Stage IIIB-IV
      NSCLC patients were randomized to DC (docetaxel 75 mg/m(2) and cisplatin 75
      mg/m(2), d1 q3w), DCb (docetaxel 75 mg/m(2) and carboplatin area under the
      concentration-time curve 6 mg/mL.min, d1 q3w), or VC (vinorelbine 25 mg/m(2), d1,
      8, 15, and 22 and cisplatin 100 mg/m(2), d1 q4w). RESULTS: Of 1218 patients, 401
      were age > or = 65 years (149/118/134 DC/DCb/VC arms). In the elderly, median
      survival was 12.6 versus 9.9 months, 1-year survival was 52% versus 41%, 2-year
      survival was 24% versus 17% for DC versus VC, respectively. DCb survival results
      were similar to those for VC: median, 9.0 months; 1-year, 38%; 2-year, 19%.
      Survival outcomes were similar between elderly and younger patients across
      treatment arms. Compared with younger patients, elderly patients reported
      moderately higher incidences of NCI CTC (version 1.0) Grade 3-4 asthenia,
      infection, and pulmonary toxicities across treatment arms, and diarrhea and
      sensory neurotoxicity for cisplatin-containing arms. Most hematologic toxicities
      occurred with similar incidences between elderly and younger patients, although
      neutropenia was slightly increased in elderly patients. CONCLUSION: First-line
      docetaxel-cisplatin chemotherapy showed similar activity in elderly and younger
      patients with advanced/metastatic NSCLC; elderly patients tolerated docetaxel
      platinum well despite experiencing slightly more toxicity than younger patients.

PMID- 16288486
TI  - Angiosarcoma of the breast.
AB  - BACKGROUND: Angiosarcoma of the breast is a rare entity. The objectives of this
      study were to evaluate prognostic factors and determine outcomes in a large
      contemporary series of patients. METHODS: Clinical and pathologic factors were
      analyzed in all patients with angiosarcoma of the breast treated between 1990 and
      2003. Overall survival (OS) and disease-free survival (DFS) were estimated using
      the methods of Kaplan and Meier. Multivariate analyses were performed to evaluate
      prognostic factors. RESULTS: Fifty-five women with angiosarcoma of the breast
      were identified. The median age was 49.1 years, and the median follow-up time was
      3.7 years. The median OS and DFS were 2.96 years and 2.26 years, respectively.
      For the 32 patients with primary angiosarcoma of the breast 5-year OS was 59%.
      Twenty-three (42%) patients had received prior radiation therapy for the
      treatment of breast cancer. These patients with radiation therapy-associated
      angiosarcoma were on average 30 years older and less likely to present with
      distant metastatic disease than patients presenting with radiation-naive
      angiosarcoma of the breast. Although radiation-naive patients appeared to have
      had better early DFS and OS, the Kaplan-Meier curves were not statistically
      different between patients with radiation therapy-associated disease and
      radiation therapy-naive patients. On multivariate analysis, tumor recurrence (P =
      0.006) was the only significant adverse prognostic factor noted for OS.
      CONCLUSIONS: In this series of 55 patients with angiosarcoma of the breast,
      radiation therapy-naive angiosarcomas occurred in younger patients, but they
      behaved similarly to radiation therapy-associated angiosarcomas.

PMID- 16288487
TI  - A population-based description of glioblastoma multiforme in Los Angeles County,
      1974-1999.
AB  - BACKGROUND: There have been reports that the incidence rates of brain tumors have
      increased over the past few decades, but most have considered all brain tumors
      together. The authors analyzed the pattern of glioblastoma multiforme (GBM)
      occurrence in Los Angeles County, California to shed light on the incidence and
      descriptive epidemiology of this type of brain tumor. METHODS: Data were obtained
      from the Los Angeles County Cancer Surveillance Program. Incidence rates were
      analyzed by gender, race, age at diagnosis, period of diagnosis (1974-1981, 1982
      1988, or 1989-1999), and socioeconomic status (SES). In addition, data were
      stratified according to anatomic subsite. A multivariate model describing changes
      in rates by each of these variables was constructed. RESULTS: Age-specific
      incidence rates (ASIR) rose sharply after age 30 years. The peak ASIR was at age
      70-74 years in males and at age 75-79 years in females. The age-adjusted
      incidence rate (AAIR) of GBM increased from 1974 to 1999 by an estimated 2.4% per
      year among males and 2.8% per year among females. Overall, males had a 60%
      increased risk of brain tumors compared with females. Males had a higher
      incidence of GBM compared with females at each anatomic subsite except the
      posterior fossa. The largest male:female ratio occurred in the occipital lobes.
      Non-Latino whites had the highest incidence rates (2.5 per 100,000) followed by
      Latino whites (1.8 per 100,000), and blacks (1.5 per 100,000). After 1989,
      compared with the period before magnetic resonance imaging (MRI) was available,
      there was an increase in GBM incidence rates among those with of higher SES that
      was most pronounced in females. The incidence of GBM was highest for frontal lobe
      tumors and for tumors that involved two or more lobes (overlapping tumors),
      followed by tumors in the temporal and parietal lobes. In the multivariate
      analysis, year of diagnosis, SES, gender, race (Latino but not black), site, and
      age at diagnosis all were important predictors of incidence rate. CONCLUSIONS:
      GBM incidence increased in Los Angeles County over the last 30 years and
      especially after 1989, suggesting that the introduction of MRI may have
      contributed to the increase. Individuals older than age 65 years experienced the
      greatest increase in incidence over time. Older age, male gender, higher SES, and
      non-Latino white race increased the risk of GBM. Previously unreported incidence
      rates for GBM among Latino whites were significantly lower than among non-Latino
      whites but were intermediate between non-Latino whites and blacks.

PMID- 16288488
TI  - Long-term survivors after gamma knife radiosurgery for brain metastases.
AB  - BACKGROUND: Stereotactic radiosurgery, with or without whole-brain radiation
      therapy, has become a valued management choice for patients with brain
      metastases, although their median survival remains limited. In patients who
      receive successful extracranial cancer care, patients who have controlled
      intracranial disease are living longer. The authors evaluated all brain
      metastasis in patients who lived for > or = 4 years after radiosurgery to
      determine clinical and treatment patterns potentially responsible for their
      outcome. METHODS: Six hundred seventy-seven patients with brain metastases
      underwent 781 radiosurgery procedures between 1988 and 2000. Data from the entire
      series were reviewed; and, if patients had > or = 4 years of survival, then they
      were evaluated for information on brain and extracranial treatment, symptoms,
      imaging responses, need for further care, and management morbidity. These long
      term survivors were compared with a cohort who lived for < 3 months after
      radiosurgery (n = 100 patients). RESULTS: Forty-four patients (6.5%) survived for
      > 4 years after radiosurgery (mean, 69 mos with 16 patients still alive). The
      mean age at radiosurgery was 53 years (maximum age, 72 yrs), and the median
      Karnofsky performance score (KPS) was 90. The lung (n = 15 patients), breast (n =
      9 patients), kidney (n = 7 patients), and skin (melanoma; n = 6 patients) were
      the most frequent primary sites. Two or more organ sites outside the brain were
      involved in 18 patients (41%), the primary tumor plus lymph nodes were involved
      in 10 patients (23%), only the primary tumor was involved in 9 patients (20%),
      and only brain disease was involved in 7 patients (16%), indicating that extended
      survival was possible even in patients with multiorgan disease. Serial imaging of
      133 tumors showed that 99 tumors were smaller (74%), 22 tumors were unchanged
      (17%), and 12 tumors were larger (9%). Four patients had a permanent neurologic
      deficit after brain tumor management, and six patients underwent a resection
      after radiosurgery. Compared with the patients who had limited survival (< 3
      mos), long-term survivors had a higher initial KPS (P = 0.01), fewer brain
      metastases (P = 0.04), and less extracranial disease (P < 0.00005). CONCLUSIONS:
      Although the expected survival of patients with brain metastases may be limited,
      selected patients with effective intracranial and extracranial care for malignant
      disease can have prolonged, good-quality survival. The extent of extracranial
      disease at the time of radiosurgery was predictive of outcome, but this does not
      necessarily mean that patients cannot live for years if treatment is effective.

PMID- 16288489
TI  - Diagnostic mammography performance and race: outcomes in Black and White women.
AB  - BACKGROUND: A previous study compared the performance (sensitivity, specificity,
      positive predictive value, and cancer detection rate) of screening mammography in
      Black and White women. No study, to the authors' knowledge, has evaluated the
      difference in the performance of diagnostic mammography between Black and White
      women. METHODS: Univariate analysis was used to evaluate differences in
      characteristics and cancers between Black and White women. Stratified and
      adjusted logistic regression analyses were used to test the association of Black
      and White race with performance measures of diagnostic mammography. RESULTS: The
      sensitivity of diagnostic mammography was higher (91% vs. 84%) and specificity
      was lower (86% vs. 90%) among Black women compared with White women. After
      controlling for age, density, self-reported breast problems, and previous
      mammography, sensitivity was significantly higher (odds ratio [OR] = 1.82, 95%
      confidence interval [CI] = 1.22-2.80) and specificity was significantly lower (OR
      = 0.75, 95% CI = 0.70-0.81) among Black women. The crude cancer detection rate of
      mammography was higher for Black women (42.6/1000) than for White women
      (31.0/1000) and Black women had a higher proportion of cancers that were > 2.0 cm
      (57.4% vs. 46.2%) that were more often poorly differentiated (61.7% vs. 49.3%)
      and were more often estrogen-receptor and progesterone-receptor negative.
      CONCLUSIONS: Black women have lower specificity of diagnostic mammography and,
      consequently, more unnecessary workups than White women. Black women have higher
      sensitivity of diagnostic mammography, with cancers that are larger and more
      advanced than White women. Delay in responding to signs and symptoms would
      explain the size and later stage. However, more research is needed to understand
      the biologic differences of breast cancer characteristics between Black and White
      women.

PMID- 16288490
TI  - The impact of early resection of primary neuroblastoma on the survival of
      children older than 1 year of age with stage 4 disease: the St. Jude Children's
      Research Hospital Experience.
AB  - BACKGROUND: It remains unclear whether primary tumor resection benefits patients
      with metastatic neuroblastoma. The authors assessed the impact of extent and
      timing of resection on outcome in these patients. METHODS: The authors reviewed
      the records of 124 patients > 1 year of age at diagnosis of International
      Neuroblastoma Staging System Stage 4 neuroblastoma. The survival estimates of
      those who did and did not have a gross total resection (GTR) and of those who had
      initial versus delayed GTR were compared. Surgical complications were reviewed.
      RESULTS: The 5-year survival estimates were comparable for the 90 patients who
      had a GTR and the 17 who underwent surgery but did not have a GTR (29.9% +/- 5.1%
      [standard error] vs. 29.4% +/- 10.1%). The 7 patients who underwent GTR at the
      time of diagnosis had a higher 5-year survival estimate than the 83 patients who
      had a GTR after induction chemotherapy (83.3% +/- 13.9% vs. 25.2% +/- 5.0%) (P =
      0.001). Five-year event-free survival estimates were similarly higher in the
      initial-GTR group (57.1% +/- 18.7% vs. 14.5% +/- 4.2%) (P = 0.002). These two
      groups did not differ significantly in age at diagnosis (P = 0.118), site of
      primary tumor (P = 0.34), MYCN amplification status (P = 1), serum lactate
      dehydrogenase activity at diagnosis (P = 0.34), or treatment protocol (P = 0.22).
      Twenty-two (21%) patients had a surgical complication. CONCLUSIONS: In this small
      cohort of patients with metastatic neuroblastoma, GTR at the time of diagnosis
      offered a survival benefit. Further prospective studies are warranted before this
      approach can be applied to all patients with metastatic neuroblastoma.

PMID- 16288491
TI  - Reduced cancer incidence among patients with schizophrenia.
AB  - BACKGROUND: The incidence of cancer in patients with schizophrenia has been
      conversely reported to be higher, lower, or similar to that in the general
      population. The effects of lifestyle factors such as excess smoking, exposure to
      neuroleptic medications, and genetic factors that may influence the incidence of
      cancer in this group are not clear. The current study was performed to evaluate
      the frequency of cancer in a large cohort of patients with schizophrenia and to
      determine the standardized incidence ratios (SIRs) of any malignancy in this
      group. METHODS: Data regarding the design, setting, and participants of the
      current study were analyzed from a cohort of 3226 patients with schizophrenia who
      were enrolled in the computerized health registry of the Abarbanel Mental Health
      Center between 1993-2003. The mean age of the patients at the time of the
      diagnosis of cancer was 49 +/- 14.7 years, with the majority of patients (61%)
      being male. All patients with schizophrenia records in the database were combined
      with the records of the Israeli National Cancer Registry to identify
      pathologically confirmed cancer comorbidity. The cancer incidence rates among
      patients with schizophrenia were compared with the expected incidence in an age
      matched and gender-matched general population sample for the same time interval.
      RESULTS: Among 1247 female patients with schizophrenia, 22 (1.8%) developed
      breast cancer and 68 (5.5%) developed cancers of any type. Fifty-two of the 1979
      male schizophrenic patients (2.6%) developed cancer. The SIRs were 0.58 (95%
      confidence interval [95% CI], 0.48-0.69) with a P value of < 0.05 for all cancers
      in the cohort, and 0.60 (95% CI, 0.37-0.90) for female breast cancer.
      CONCLUSIONS: The results of the current study demonstrate a reduced risk of
      cancer in patients with schizophrenia. The mechanisms responsible for the lower
      risk need be investigated further.

PMID- 16288492
TI  - L-asparaginase as a marker of chemotherapy dose modification in children with
      acute lymphoblastic leukemia.
AB  - BACKGROUND: The objective of the current study was to compare chemotherapy dose
      modifications in obese (a body mass index [BMI] > 95%) and nonobese (a BMI < or =
      95%) pediatric patients with acute lymphoblastic leukemia (ALL). METHODS: The
      study cohort was comprised of 199 pediatric patients diagnosed with ALL who were
      treated at 1 of 2 South Texas pediatric oncology centers between 1990-2000. The
      relative chemotherapy dose modification during the induction phase of
      chemotherapy was calculated as the ratio of 1) the actual administered dose of L
      asparaginase and 2) the protocol-calculated dose of L-asparaginase. The extent to
      which the chemotherapy dose modification varied according to obesity status was
      assessed using stratified Student t tests and an ordinary least-squares
      regression analysis. RESULTS: Obese ALL patients were found to exhibit a 7%
      decrease in the mean relative modification of L-asparaginase during induction
      chemotherapy compared with their nonobese counterparts. This finding was
      statistically significant (P = 0.009), even after adjustment for gender, age,
      ethnicity, and clinical institution. CONCLUSIONS: To the authors' knowledge, the
      current study is the first published report of an obesity-associated chemotherapy
      dose modification in pediatric patients with ALL, the most common childhood
      malignancy. It will be important to examine whether these findings are consistent
      with those observed in future studies, and ultimately to assess the association
      between obesity-related dose modifications and long-term cancer outcomes.

PMID- 16288493
TI  - Human mesenchymal stem cells (hMSCs) expressing truncated soluble vascular
      endothelial growth factor receptor (tsFlk-1) following lentiviral-mediated gene
      transfer inhibit growth of Burkitt's lymphoma in a murine model.
AB  - BACKGROUND: Efficient gene transfer to bone marrow derived mesenchymal stem cells
      (MSC) would provide an important opportunity to express potent anticancer agents
      in the tumour microenvironment because of their contribution to the tumour
      stroma. METHODS: HIV-based lentiviral vectors were pseudotyped with four
      different envelope proteins; amphotropic murine leukaemia virus (ampho), murine
      leukaemia virus (10A1), feline endogenous virus (RD114), and the vesicular
      stomatitis virus glycoprotein (VSVG). These pseudotypes were examined for
      transduction efficiency in human bone marrow derived MSC. The effect of
      lentiviral expression of truncated soluble vascular endothelial growth factor
      decoy receptor (tsFlk-1) in MSC on growth of Raji cells was determined, both in
      vitro and in vivo. RESULTS: All lentiviral vectors produced significant levels of
      transduction at an multiplicity of infection (MOI) of 1, those bearing the RD114
      envelope glycoprotein consistently produced higher transduction levels (mean 70
      +/- 6%) compared with the other pseudotyped lentiviral vectors, although there
      was significant inter-donor variation. Stable transgene expression was achieved
      after multiple rounds of transduction with VSVG-pseudotyped particles, without
      alteration in the differentiative capacity of transduced cells. Co-injection of
      MSC stably expressing tsFlk-1 with Raji Burkitt's lymphoma cells significantly
      impaired subcutaneous tumour growth in immunodeficient mice when compared to
      controls where either unmanipulated MSC or GFP-expressing MSC were used.
      CONCLUSIONS: Human MSC are easily transduced by pseudotyped lentiviral particles
      but there is inter-donor variation in transduction efficiency. Gene-modified MSC
      expressing a gene of therapeutic potential can moderate growth of haematological
      malignancies.

PMID- 16288494
TI  - Polybrene improves transfection efficacy of recombinant replication-deficient
      adenovirus in cutaneous cells and burned skin.
AB  - BACKGROUND: The hostile environment found in acute and chronic wounds decreases
      the physiological half-life of purified synthetic or recombinant peptides
      dramatically. Gene therapy, on the other hand, may be a viable option since it
      relies on the cellular machinery of the host to locally manufacture the proteins
      of interest. The aim of this study was to evaluate and optimize the local
      administration of transient cutaneous adenoviral gene delivery in wounds.
      METHODS: Primary human keratinocytes (HKC) and HaCaT cells were transfected with
      replication-deficient adenovirus (Ad5) containing the reporter gene for beta
      galactosidase (LacZ). The vector was used alone or precoated with either (1)
      Lipofectamine 2000, (2) FuGENE 6, or (3) Polybrene. For in vivo testing a rat
      burn model was used. Animals were randomized into three groups: (1) Ad5-LacZ
      alone; (2) Ad5-LacZ precoated with Polybrene, or (3) carrier control (phosphate
      buffered saline (PBS)). Samples were harvested from burned and unburned tissue
      sections after either 48 h or 7 days. Transgene expression was quantified by
      bioluminometric assay and localized using immunohistochemistry. A BrdU assay was
      performed to determine the influence of the used transfection reagents on cell
      proliferation. RESULTS: Transfection efficacy was significantly improved in vitro
      (p < 0.001) as well as in partial thickness burned (p = 0.015) and unburned skin
      (p > 0.001) after precoating Ad5 with Polybrene compared to Ad5 alone. Transgene
      expression was 10-fold higher in burned skin (9305 pg/mg protein) compared to
      unburned skin (859 pg/mg protein). CONCLUSIONS: It is feasible to improve
      transfection efficacy in vitro and in vivo by precoating the adenovirus with
      Polybrene.

PMID- 16288495
TI  - A system for efficient generation of adenovirus protein IX-producing helper cell
      lines.
AB  - BACKGROUND: The adenovirus 14.3 kDa hexon-associated protein IX (pIX) functions
      in the viral capsid as 'cement' and assembles the hexons in stable groups-of-nine
      (GONs). Although viruses lacking pIX do not form GONs, and are less heat-stable
      than wild-type (wt) viruses, they can be propagated with the same kinetics and
      yields as the wt viruses. To facilitate 'pseudotyping' of adenoviral vectors we
      have set up an efficient system for the generation of pIX-producing helper cell
      lines. METHODS: With a lentiviral pIX-expression cassette, monoclonal and
      polyclonal helper cell lines were generated, which express wt or modified pIX
      genes at levels equivalent to wt HAdV-5 infected cells. The incorporation
      efficiency into pIX gene deleted viruses was examined by Western analysis, immuno
      affinity electron microscopy, and heat-stability assays. RESULTS: Immuno-affinity
      electron microscopy on viruses lacking the pIX gene demonstrated that more than
      96% of the particles contain pIX protein in their capsids after propagation on
      the pIX-expressing helper cell lines. In addition, the pIX level in the helper
      cells was sufficient to generate heat-stable particles. Finally, the ratio
      between pIX and fiber was equivalent to that found in wt particles. The pIX
      producing cell lines are very stable, demonstrating that pIX is not toxic to
      cells. CONCLUSION: These data demonstrate that lentivirus vectors can be used for
      the establishment of pIX-complementing helper cell lines.

PMID- 16288496
TI  - Comparative analysis of antitumor activity of CD40L, RANKL, and 4-1BBL in vivo
      following intratumoral administration of viral vectors or transduced dendritic
      cells.
AB  - The tumor necrosis factor (TNF) family comprises a group of ligands that regulate
      cell proliferation, differentiation, activation, maturation and apoptosis through
      interaction with the corresponding TNF receptor family members. In this study, we
      have evaluated whether adenovirus-mediated intratumoral gene transfer of CD40L,
      RANKL, or 4-1BBL elicits an immune response to established murine MC38 and TS/A
      tumors. Intratumoral administration of the recombinant adenoviral vectors
      expressing CD40L, RANKL or 4-1BBL 7 days post-tumor cell inoculation resulted in
      significant inhibition of MC38 tumor growth for all three ligands when compared
      with control groups treated with either saline or control adenovirus. However,
      intratumoral injection of Ad-4-1BBL or Ad-CD40L resulted in a significantly
      stronger inhibition of TS/A tumor progression than did Ad-RANKL treatment. We
      also demonstrated that intratumoral administration of dendritic cells (DC)
      transduced with adenoviral vectors encoding the TNF-related ligands resulted in a
      significant inhibition of MC38 tumor growth as compared with control groups
      treated with Ad-LacZ-transduced DC or saline-treated DC. In addition, DC
      overexpressing CD40L secreted considerably more IL-12 and expressed higher levels
      of the co-stimulatory molecules, CD80, CD86 and CD40, than did DC overexpressing
      LacZ, 4-1BBL or RANKL. We have also demonstrated that DC/CD40L, DC/4-1BBL, and
      DC/RANKL survived significantly longer than control DC or DC infected with the
      LacZ vector. Taken together, these results demonstrate that adenoviral gene
      transfer of CD40L, RANKL or 4-1BBL elicit a significant antitumor effect in two
      different tumor models, with CD40L gene transfer inducing the strongest antitumor
      effect.

PMID- 16288497
TI  - From pathogen to medicine: HIV-1-derived lentiviral vectors as vehicles for
      dendritic cell based cancer immunotherapy.
AB  - Over the years, the unique capacity of dendritic cells (DC) for efficient
      activation of naive T cells has led to their extensive use in cancer
      immunotherapy protocols. In order to be able to fulfil their role as antigen
      presenting cells, the antigen of interest needs to be efficiently introduced and
      subsequently correctly processed and presented by the DC. For this purpose, a
      variety of both viral and non-viral antigen-delivery systems have been evaluated.
      Amongst those, HIV-1-derived lentiviral vectors have been used successfully to
      transduce DC. This review considers the use of HIV-1-derived lentiviral vectors
      to transduce human and murine DC for cancer immunotherapy. Lentivirally
      transduced DC have been shown to present antigenic peptides, prime transgene
      specific T cells in vitro and elicit a protective cytotoxic T-lymphocyte (CTL)
      response in animal models. Different parameters determining the efficacy of
      transduction are considered. The influence of lentiviral transduction on the DC
      phenotype and function is described and the induction of immune responses by
      lentivirally transduced DC in vitro and in vivo is discussed in detail. In
      addition, direct in vivo administration of lentiviral vectors aiming at the
      induction of antigen-specific immunity is reviewed. This strategy might overcome
      the need for ex vivo generation and antigen loading of DC. Finally, future
      perspectives towards the use of lentiviral vectors in cancer immunotherapy are
      presented.

PMID- 16288498
TI  - Stimulatory effect of polyethylene glycol (PEG) on gene expression in mouse liver
      following hydrodynamics-based transfection.
AB  - BACKGROUND: Rapid intravenous injection of a large volume of plasmid DNA (pDNA),
      i.e. a transfection procedure based on hydrodynamics, is known to be an efficient
      and liver-specific method of in vivo gene delivery. However, the gene expression
      is transient. METHODS: We investigated the effect of addition of polyethylene
      glycol (PEG) to a solution of naked pDNA (luciferase) on the expression of the
      gene in mouse liver following transfection by the hydrodynamics-based technique.
      In addition, the mechanism leading to the enhancement of the gene expression was
      studied. RESULTS: The addition of 1% (w/v) PEG2000 to the pDNA solution enhanced
      the resulting gene expression in the liver. Increasing the PEG2000 concentration
      to more than 1 and up to 10% (w/v) rather diminished the gene expression level.
      By contrast, increasing the molecular weight of PEG to over 2000 up to 10 000 did
      not affect the level of gene expression. Histopathological and serum-chemistry
      examinations indicated that hydrostatic or osmotic pressure increased tissue and
      hepatocellular damage in a PEG-concentration-dependent manner, and resulted in a
      decrease in gene expression. Quantitative evaluation showed that the enhanced
      gene expression resulted from stabilization of the pDNA introduced into the
      hepatocytes and an enhancement of the transport of intact pDNA to the nucleus.
      CONCLUSIONS: For most gene therapy applications and gene function studies,
      sustained expression of the introduced gene(s) is necessary. This simple method
      to achieve enhanced gene expression in liver may have a great potential for a
      wide variety of laboratory studies in molecular and cellular biology as well as
      possibly for future clinical applications in humans.

PMID- 16288499
TI  - Efficient cold transfection of pea ferredoxin-NADP(H) oxidoreductase into rat
      hepatocytes.
AB  - We describe the use of a non-viral, polyethylenimine-based vector to transfect
      rat hepatocytes preserved under hypothermic storage. DNA sequences encoding
      Escherichia coli beta-galactosidase and pea ferredoxin-NADP(H) oxidoreductase
      (FNR), cloned into plasmids pCH110 and pKM4 respectively, were used. FNR was
      detected in the liver of animals transplanted with transfected cells; no
      reactivity was observed in endogenous parenchyma. The expression of the transgene
      was transient as it was detectable up to 96 h subsequently declining to
      undetectable levels. In contrast to non-transfected cells, the engraftment of FNR
      positive cells was not associated with inflammatory reaction. The percentage of
      FNR-positive implanted hepatocytes was at least five times higher than the
      original transfection efficiency measured in vitro, while the percentage of beta
      galactosidase-positive cells was similar for both methods. These data indicate
      that the transfection system is effective in the transfer of plasmid DNA into
      hepatocytes under cold preservation and suggest the advantage of pKM4-transfected
      hepatocytes on engraftment in the recipient parenchyma.

PMID- 16288500
TI  - Study of ethanol-induced conformational changes of holo and apo alpha-lactalbumin
      by spectroscopy and limited proteolysis.
AB  - This study was performed to contribute to the analysis of alpha-lactalbumin
      "molten globule" state by using spectral and proteolysis techniques. Samples of
      holo and apo alpha-lactalbumin in the presence of different concentrations of
      ethanol were analyzed. Results of fluorescence spectroscopy of both forms showed
      that as ethanol concentration increased, the tryptophanyl residues became more
      accessible to the solvent. Near circular dichroism spectra of holo alpha
      lactalbumin indicated that its tertiary structure was maintained in 20% ethanol
      whereas it was altered in 30 and 40% ethanol. For apo alpha-lactalbumin, spectra
      were similar in all samples studied. Holo alpha-lactalbumin was resistant to
      trypsinolysis in 0% ethanol, whereas it was easily hydrolyzed in 20 and 30%
      ethanol. In the case of the apo form and in the absence of ethanol, 70% of the
      protein was degraded after 1 h. However, in the presence of 20 and 30% ethanol,
      the overall reaction rate was lowered. Peptides obtained after tryptic hydrolysis
      were identified by reversed-phase high-performance liquid chromatography coupled
      to mass spectrometry. Differences in population of produced peptides indicate the
      changes of folding intermediates present in the studied alpha-lactalbumin
      solutions. This study demonstrated that proteolytic enzymes are suitable tools to
      determine protein structure complementing physico-chemical studies.

PMID- 16288501
TI  - Anthocyanidins decrease endothelin-1 production and increase endothelial nitric
      oxide synthase in human endothelial cells.
AB  - Epidemiological and intervention studies correlate anthocyanin-rich beverages and
      a low incidence of coronary heart diseases. Since endothelin-1 (ET-1) and nitric
      oxide (NO) produced by endothelial NO synthase (eNOS) are vascular tension
      regulators secreted by endothelial cells, we studied the influence of two
      anthocyanidins, namely cyanidin (CY) and delphinidin (DP), on the regulation of
      ET-1 and eNOS in cultured human umbilical vein endothelial cells (HUVECs).
      Aglycon anthocyanidin forms, such as CY and DP, may be present in vivo after the
      first deglycosylation step occurring in the jejunum and in the liver. DP showed a
      major action compared to CY inducing a significant dose-dependent inhibitory
      effect on both protein and mRNA levels of ET-1. CY and DP both increased the
      protein level of eNOS, but DP showed the major effect raising eNOS protein in a
      dose-dependent manner. To correlate the vasoprotective effect of CY and DP with
      their antioxidant activity, we analysed also the antioxidant effect of
      anthocyanidins both in vitro and in HUVECs. In particular, we examined the effect
      of anthocyanidins on endothelial heme oxygenase-1 (HO-1), an inducible stress
      protein. In all tests, DP showed a higher antioxidant activity than CY. Finally,
      the antiproliferative effect induced by DP was detected in HUVECs. DP and CY
      differ in the number and position of hydroxyl groups in their structure;
      therefore, the greater biological activity by DP, compared with CY, seems to be
      due to the presence of the three hydroxyl groups on the B ring in the molecular
      structure of DP.

PMID- 16288503
TI  - Asymmetric synthesis of multifunctionalized pyrrolines by a ruthenium porphyrin
      catalyzed three-component coupling reaction.
AB  - [reaction: see text] Chiral multifunctionalized pyrrolines have been synthesized
      by a ruthenium porphyrin catalyzed three-component coupling reaction. In a one
      pot reaction, ruthenium porphyrins catalyzed in situ generation of chiral
      azomethine ylides from chiral diazo esters and imines. Asymmetric 1,3-dipolar
      cycloaddition reactions of the chiral azomethine ylides with dipolarophiles
      afforded the corresponding pyrrolines in good yields and high
      diastereoselectivity (up to 92% de).

PMID- 16288502
TI  - Cloning of oleosin, a putative new hazelnut allergen, using a hazelnut cDNA
      library.
AB  - The clinical presentation of non-pollen related allergy to hazelnut can be severe
      and systemic. So far, only a limited number of non-pollen related hazelnut
      allergens have been identified and characterized. The aim of this study was to
      identify and clone new hazelnut allergens. A lambda ZAP cDNA library of hazelnut
      was constructed. The library was screened with serum of six hazelnut allergic
      patients displaying different IgE-binding patterns on hazelnut immunoblot. Rapid
      amplification of cDNA ends (RACE) protocols were applied to obtain full-length
      clones. Expression experiments were carried out in Eschericchia coli. Expression
      was monitored by SDS-PAGE, protein staining and immunoblotting. A hazelnut cDNA
      library was constructed. IgE screening resulted in the cloning of two isoforms of
      a novel putative hazelnut allergen. The clones were identified as oleosins, with
      theoretical molecular masses of 16.7 and 14.7 kDa and pI of 10.5 and 10.0,
      respectively. The isoforms demonstrated only 37% amino acid sequence identity but
      contained the typical hydrophobic stretch in the middle of the protein (53%
      identity) with the characteristic oleosin proline knot region (11/12 amino acids
      identical). Expression in E. coli of the longer isoform resulted in a clear band
      on SDS-PAGE. The expressed protein was recognized on an immunodot blot by IgE
      from serum that was used for screening the cDNA library. Hazelnut contains
      multiple isoforms of oleosin. IgE binding of a hazelnut-allergic patient to a
      recombinant version suggest that hazelnut oleosin is an allergen, as has been
      described for peanut and sesame.

PMID- 16288504
TI  - Enantioselective synthesis of furo[2,3-b]furans, a spongiane diterpenoid
      substructure.
AB  - [structure: see text] A short and enantioselective synthesis of cis-fused 5
      oxofuro[2,3-b]furans, being found in many spongiane diterpenoid natural products,
      is reported starting from inexpensive methyl 2-furoate. Moreover, the acid
      catalyzed rearrangement of the furo[2,3-b]furan framework A to B is observed for
      some derivatives, suggesting a simple connection between natural products
      differing in the absolute configuration of the 3a,6a ring junction.

PMID- 16288505
TI  - Anion recognition using preorganized thiourea functionalized [3]polynorbornane
      receptors.
AB  - [structure: see text] A new family of [3]polynorbornane frameworks exhibiting
      conformationally preorganized aromatic thiourea (cleft-like) receptors have been
      designed and synthesized for anion recognition. These show excellent affinity for
      the biologically relevant dihydrogenphosphate (H(2)PO(4)(-)) and
      dihydrogenpyrophosphate (H(2)P(2)O(7)(2)(-)) anions (among others), which are
      bound in 1:1 and 2:1 (host:anion) ratio, respectively. Moreover, visually
      striking color changes accompany guest binding, enabling this family to act as
      colorimetric anion sensors.

PMID- 16288506
TI  - Nonconjugated hybrid of carbazole and fluorene: a novel host material for highly
      efficient green and red phosphorescent OLEDs.
AB  - [structure: see text] A novel host material for efficient green and red
      electrophosphorescence devices is obtained by adopting the new molecular strategy
      of nonconjugated linkage of carbazole and fluorene moieties. The new host
      combines characteristics of both carbazole and fluorene, giving a large-gap host
      material suitable for green and red phosphorescent OLEDs. Green and red
      phosphoresecent OLEDs with external quantum efficiencies up to 10% have been
      achieved with this new host material.

PMID- 16288507
TI  - Synthesis, crystal structure, and nonlinear optical behavior of beta
      unsubstituted meso-meso E-vinylene-linked porphyrin dimers.
AB  - [structure: see text] A vinylene-linked porphyrin dimer, with no substituents at
      the beta-positions, has been synthesized by CuI/CsF promoted Stille coupling. In
      the crystal structure of this dimer, the C(2)H(2) bridge is twisted by 45 degrees
      relative to the plane of the porphyrins. The absorption, emission spectra, and
      electrochemistry reveal substantial porphyrin-porphyrin pi-conjugation. The
      triplet excited-state absorption spectrum of this dimer makes it suitable for
      reverse saturable absorption at 710-900 nm.

PMID- 16288508
TI  - O-Directed free-radical hydrostannations of propargyl ethers, acetals, and
      alcohols with Ph3SnH and Et3B.
AB  - [reaction: see text] The O-directed hydrostannation of various propargyloxy
      substrates is reported with Ph(3)SnH/Et(3)B.

PMID- 16288509
TI  - On the stereospecific conversion of proximally-oxygenated trisubstituted
      vinyltriphenylstannanes into stereodefined trisubstituted alkenes.
AB  - [reaction: see text] Allylically oxygenated vinyl alpha-triphenylstannanes such
      as 22 can be readily converted into vinyl iodides and thereafter stereodefined
      trisubstituted alkenes with retention of configuration.

PMID- 16288510
TI  - Mechanistic studies on the O-directed free-radical hydrostannation of
      disubstituted acetylenes with Ph3SnH and Et3B and on the iodination of
      allylically oxygenated alpha-triphenylstannylalkenes.
AB  - [reaction: see text] The free-radical hydrostannation of 1 with Ph(3)SnH and
      catalytic Et(3)B in PhMe has been mechanistically probed. At high Ph(3)SnH
      concentrations, the O-directed hydrostannation pathway dominates, and 2 is formed
      with good selectivity (ca. 11.1:1). Substantially lower stannane/substrate
      concentrations increase the amount of tandem 5-exo-trig cyclization product 3
      that is observed.

PMID- 16288511
TI  - Electrochemically assisted Heck reactions.
AB  - [reaction: see text] During efforts to develop chip-based Heck reaction
      chemistry, it was discovered that normal solution-phase Heck reactions can be
      dramatically accelerated using electrochemistry. The acceleration makes room
      temperature Heck reactions proceed at synthetically useful rates in the absence
      of added ligand. Presumably, the current passed through the reaction maintains a
      high level of active catalyst.

PMID- 16288512
TI  - Reaction of benzoylnitrene with anions: formation of an intermediate in the
      Hofmann rearrangement.
AB  - [reaction: see text] Nucleophilic anions react rapidly with benzoylnitrene to
      form a species involved in the Hofmann rearrangement. This species has been
      detected by time-resolved infrared spectroscopy.

PMID- 16288513
TI  - Convenient synthesis of N-unprotected deoxynucleoside 3'-phosphoramidite building
      blocks by selective deacylation of N-acylated species and their facile conversion
      to other N-functionalized derivatives.
AB  - [reaction: see text] A new route to N-unprotected deoxynucleoside 3'
      phosphoramidite building blocks by use of highly selective N-deacylation of
      commercially available N-acylated deoxynucleoside 3'-phosphoramidites is
      described. These compounds could be readily converted to other types of N
      protected species by facile N-acylations with acylating reagents.

PMID- 16288514
TI  - Asymmetric conjugate addition of copper reagents to alpha,beta-unsaturated tert
      butanesulfinyl imines.
AB  - [reaction: see text] Addition of organocuprates to N-sulfinyl alpha,beta
      unsaturated imines proceeds in good yields and with good diastereoselectivities.
      alpha,beta-Unsaturated sulfinyl ketimines and aldimines have both been shown to
      be suitable substrates for this reaction.

PMID- 16288515
TI  - Nonracemic alpha-allenyl carbinols from asymmetric propargylation with the 10
      trimethylsilyl-9-borabicyclo[3.3.2]decanes.
AB  - [reaction: see text] The asymmetric propargylboration of aldehydes at -78 degrees
      C in <3 h with 1 provides silylated alpha-allenyl carbinols 6 (60-87%) in high ee
      (94% to >98% ee). The reagents 1 are easily prepared in both enantiomeric forms
      with a simple Grignard procedure and air-stable borinate complexes 2. The
      ozonolysis of 6 proceeds smoothly through an acylsilane intermediate to give a
      TMS ester, which is hydrolyzed to the alpha-hydroxy acid quantitatively with
      water.

PMID- 16288516
TI  - Electrophilic activation of lactams with Tf2O and pyridine: expedient synthesis
      of (+/-)-tetraponerine T4.
AB  - [reaction: see text] The electrophilic activation of lactams with triflic
      anhydride in the presence of pyridine was investigated by NMR. It was found that
      2-pyrrolidone led to the clean formation of the corresponding pyridinium imidate
      in 89% isolated yield. The subsequent nucleophilic addition of organometallic
      reagents led to 2-substituted dihydropyridines. A synthesis of (+/-)
      tetraponerine T4 with three simple building blocks was accomplished in 3 steps
      (38% yield).

PMID- 16288517
TI  - Synthesis of a 2,3';6',3''-terpyridine scaffold as an alpha-helix mimetic.
AB  - [reaction: see text] A terpyridine scaffold has been designed as an alpha-helix
      mimetic. A facile synthesis of the ortho-functionalized 2,3'-oligopyridine has
      been accomplished using sequential Bohlmann-Rahtz heteroannulation reactions.

PMID- 16288518
TI  - Gold-catalyzed cyclization of (Z)-2-en-4-yn-1-ols: highly efficient synthesis of
      fully substituted dihydrofurans and furans.
AB  - [reaction: see text] The gold-catalyzed cyclization of (Z)-enynols offers an
      efficient and straightforward route to stereodefined (Z)-5-ylidene-2,5
      dihydrofurans and fully substituted furans under extremely mild reaction
      conditions. Importantly, the results indicated that both the oxyauration and the
      proto-demetalation steps are highly stereoselective.

PMID- 16288519
TI  - Asymmetry by electrophilic rearrangement of symmetric 2-pyridone photodimers.
AB  - [reaction: see text] Halogenation of achiral trans-2-pyridone photodimers results
      in 1,3-migration of an amide nitrogen and formation of a chiral structure with
      six stereogenic centers and well-differentiated functionality. The reactivity of
      this product toward nucleophiles, including the allylic halide, is dominated by
      participation by the amide nitrogen.

PMID- 16288520
TI  - A new method for translating the asymmetric Ni/Cr-mediated coupling reactions
      from stoichiometric to catalytic.
AB  - [reaction: see text] A new method has been developed for effectively translating
      the degree of asymmetric induction and the chemical yield achieved in the
      stoichiometric asymmetric Ni/Cr-mediated coupling to a catalytic asymmetric
      process via a chiral sulfonamide ligand. It has also been shown that the Ni
      catalyst plays a central role. Among a number of the Ni catalysts, the 2,9
      dimethylphenanthroline/NiCl(2) complex (7) has been found to be the most
      effective.

PMID- 16288521
TI  - Surprisingly efficient catalytic Cr-mediated coupling reactions.
AB  - [reaction: see text] With use of 1 mol % of Cr catalyst 5, surprisingly efficient
      Cr-mediated couplings of aldehydes with various types of nucleophiles have been
      realized. The catalyst set of Cr catalyst 5 and Ni catalyst 4 is used for
      alkenylation, alkynylation, and arylation, whereas the catalyst set of Cr
      catalyst 5 and CoPc (cobalt phthalocyanine) is used for 2-haloallylation,
      alkylation, and propargylation. Only the Cr catalyst 5 is required for
      allylation. The reaction rates in DME and THF have been found significantly
      faster than that in MeCN.

PMID- 16288522
TI  - Ru-Catalyzed asymmetric hydrogenation of alpha-ketoesters with CeCl3.7H2O as
      additive.
AB  - [reaction: see text] An efficient asymmetric hydrogenation of alpha-ketoesters is
      reported with use of a catalyst prepared from [Ru((S)-3)(benzene)Cl]Cl and
      CeCl(3).7H(2)O. Alpha-hydroxy esters are obtained in up to 96% ee. The addition
      of CeCl(3).7H(2)O not only improves the enantioselectivity, but also enhances the
      stability of the catalyst. As a result, the hydrogenation of methyl
      benzoylformate affords the product with 92% ee with a substrate/catalyst ratio of
      10 000. Hydrolysis of 2 provides the final compound with 83% yield at 99% ee
      after a single recrystallization from 1,2-dichloroethylene.

PMID- 16288523
TI  - Room temperature intramolecular hydro-O-alkylation of aldehydes: sp3 C-H
      functionalization via a Lewis acid catalyzed tandem 1,5-hydride
      transfer/cyclization.
AB  - [reaction: see text] The scope and limitations of intramolecular hydro-O
      alkylation of aldehyde substrates leading to spiroketals and bicyclic ketals and
      aminals is reported. The direct transformation of tertiary and sterically
      hindered secondary sp(3) C-H bonds into C-O bonds under the action of a catalytic
      amount of a variety of Lewis acids is described. The mechanism of these
      transformations is proposed to involve a tandem hydride transfer/cyclization
      sequence.

PMID- 16288524
TI  - Deconjugation of dehydroamino acids: stereoselective synthesis of racemic (E)
      vinylglycines.
AB  - [reaction: see text] A practical and general two-step synthesis of carbamate
      protected (E)-vinylglycines from aliphatic aldehydes is reported. The key step
      involves the kinetic alpha-protonation of dianionic dienolates derived from
      dehydroamino acids.

PMID- 16288525
TI  - Intramolecular alkyne hydroalkoxylation and hydroamination catalyzed by iridium
      hydrides.
AB  - [reaction: see text] Iridium(III) hydrides prove to be air-stable active
      catalysts for intramolecular hydroalkoxylation and hydroamination of internal
      alkynes with proximate nucleophiles. The cyclization follows highly selective 6
      endo-dig regiochemistry when regioselectivity is an issue.

PMID- 16288526
TI  - Synthesis of conformationally constrained C-glycosyl alpha- and beta-amino acids
      and sugar-carbamino sugar hybrids via Diels-Alder reaction.
AB  - [structure: see text] Sugar-derived dienes undergo Diels-Alder reactions with
      methyl alpha-nitro acrylate and ethyl beta-nitro acrylate to form the
      corresponding cycloadducts which have been converted into conformationally
      constrained C-glycosyl alpha- and beta-amino acids. Further, these beta-amino
      acids are converted into sugar-carbamino sugar hybrid molecules.

PMID- 16288527
TI  - Aromatic core-modified twisted heptaphyrins[1.1.1.1.1.1.0]: syntheses and
      structural characterization.
AB  - [reaction: see text] First examples of aromatic core-modified twisted
      heptapyrrolic systems with six meso links have been obtained via a general [3 +
      4] acid-catalyzed condensation method. Despite the twisted conformation, these
      heptaphyrins exhibit aromaticity in solution, unlike most of the all-aza
      analogues.

PMID- 16288528
TI  - Dragmacidin E synthesis studies. Preparation of a model cycloheptannelated indole
      fragment.
AB  - [reaction: see text] The conversion of N-2,2-dichloropropionyl indole methyl
      ester into a tetracyclic cycloheptannelated indole model compound for the
      synthesis of dragmacidin E was accomplished in 10 steps. Key reactions include a
      Witkop cyclization to fashion a C-C bond at C(4) of the indole nucleus and a
      subsequent Dieckmann cyclization to deliver the desired cycloheptanoid ring.

PMID- 16288529
TI  - Chromium-mediated synthesis of polycyclic aromatic compounds from halobiaryls.
AB  - [reaction: see text] Reaction of 2,2'-dihalobiphenyl with butyllithium followed
      by the addition of chromium(III) chloride and alkynes afforded the corresponding
      phenanthrene derivatives via formal [4 + 2] cycloaddition. A variety of alkynes
      could be used for this reaction, such as alkyl, aryl, silyl, and alkoxycarbonyl
      alkynes. Repetitive process of the reaction gave more extended polycyclic
      compounds such as benzo[g]chrysene and azacyclopentaphenalene derivatives.

PMID- 16288530
TI  - Regioselective C-2 and C-6 substitution of (S)-nicotine and nicotine derivatives.
AB  - [reaction: see text] Regioselective deprotonations of (S)-nicotine and
      derivatives at the C-2 and C-6 positions of the pyridine ring were performed in
      good to excellent yields. These methodologies allow the direct introduction of a
      plethora of functional groups onto the pyridine ring of nicotine.

PMID- 16288531
TI  - Synthesis of the 4-azatricyclo[5.2.2.0(4,8)]undecan-10-one core of daphniphyllum
      alkaloid calyciphylline A using a Pd-catalyzed enolate alkenylation.
AB  - [reaction: see text] The ABC ring system of the natural product calyciphylline A
      has been synthesized. The key steps were a palladium-catalyzed intramolecular
      coupling of an amino-tethered vinyl bromide with a ketone using potassium
      phenoxide as the base to generate the C-ring and a hydroxyl-directed
      hydrogenation of an exocyclic double bond to give the azatricyclic ketone 1.

PMID- 16288532
TI  - Short and efficient total synthesis of fraxinellone limonoids using the
      stereoselective Oshima-Utimoto reaction.
AB  - [reaction: see text] The catalytic diastereoselective Oshima-Utimoto reaction was
      employed for the construction of fraxinellone and related members of this
      limonoid family of natural products. After formation of the five-membered
      lactone, a stereoselective aldol reaction and olefin metathesis established the
      bicyclic ring system in the natural products.

PMID- 16288533
TI  - New chromogenic probes into nanoscopic pockets in enhanced sensing protocols for
      amines in aqueous environments.
AB  - [structure: see text] A new sensory MCM-41-based material for the colorimetric
      sensing and discrimination of amines has been developed.

PMID- 16288534
TI  - Design of hydrogen bond catalysts based on a modular oxazoline template:
      application to an enantioselective hetero Diels-Alder reaction.
AB  - [reaction: see text] A catalyst system that displays two hydrogen bond donating
      arms from a rigid oxazoline backbone and its utility in a hydrogen bond promoted
      enantioselective hetero Diels-Alder reaction are described.

PMID- 16288535
TI  - Efficient solid-phase synthesis of trifunctional probes and their application to
      the detection of carbohydrate-binding proteins.
AB  - [structure: see text] An efficient solid-phase synthesis of trifunctional probes
      containing a photoreactive group, a reporter tag, and a carbohydrate ligand was
      developed. Labeling studies with these probes demonstrate that specific lectins
      can be labeled with high sensitivity and selectivity. This technique serves as a
      powerful tool for the rapid detection and profiling of lectins.

PMID- 16288536
TI  - Highly selective two-photon chemosensors for fluoride derived from organic
      boranes.
AB  - [reaction: see text] Three organoboron compounds are shown to be two-photon
      fluorescent sensors for fluoride anion with high sensitivity and selectivity. The
      recognition mechanism is attributed to the unique steric structure of the bulky
      dimesitylboryl group and the Lewis acid-base interaction between trivalent boron
      atom and fluoride anion.

PMID- 16288537
TI  - Structurally simple, modular amino alcohols for the recognition of carboxylic
      acids. Application to the development of a new chiral solvating agent.
AB  - [structure: see text] Two flexible receptors for carboxylic acids, based on 1
      amino-3-fluoro-2-alcohol functional arrays and built on aminomethylpyridine
      platforms, are described. The C(2)-symmetric one [from 2,6
      bis(aminomethyl)pyridine] has been shown to be an efficient CSA due to its
      ability to form geometrically different diastereomeric complexes enabling the
      discrimination between the enantiomers of a series of carboxylic acid in the (1)H
      NMR spectra.

PMID- 16288538
TI  - A stereochemically well-defined rhodium(III) catalyst for asymmetric transfer
      hydrogenation of ketones.
AB  - [reaction: see text] A rhodium(III) catalyst for asymmetric transfer
      hydrogenation of ketones has been designed. The incorporation of a tethering
      group between the diamino group and the cyclopentadienyl unit provides extra
      stereochemical rigidity. The catalyst is capable of enantioselective reduction of
      a range of ketones in excellent ee using formic acid/triethylamine as both the
      solvent and the reducing agent.

PMID- 16288539
TI  - A new general method for the preparation of N-sulfonyloxaziridines.
AB  - [reaction: see text] A simple procedure to obtain N-alkylsulfonyl- and N
      arylsulfonyloxaziridines from the corresponding N-sulfinylimines involving a one
      pot, two-step oxidation process with m-CPBA (1 equiv) and m-CPBA/KOH (1.1 equiv)
      is reported. The method is applicable to N-sulfinylimines derived from aldehydes
      (aliphatic and aromatic) and ketones (dialkyl and aryl alkyl) and preserves C=C
      conjugated double bonds. Almost quantitative yields, very mild conditions
      (usually less than 5 min at room temperature), and easy purification by
      filtration are the main features of this new procedure, which can be performed at
      a gram scale.

PMID- 16288540
TI  - N,O-isopropylidenated threonines as tools for peptide cyclization: application to
      the synthesis of mahafacyclin B.
AB  - [structure: see text] The influence of a single N,O-isopropylidenated threonine
      turn-inducer on the cyclization of a linear heptapeptide precursor to
      mahafacyclin B has been investigated. Incorporation of an N,O-isopropylidenated
      threonine more than doubles the head-to-tail cyclization yield. The N,O
      isopropylidene grouping is then readily disassembled to give the antimalarial
      cyclic peptide in high yield.

PMID- 16288541
TI  - Synthesis of the A-B subunit of angelmicin B.
AB  - [reaction: see text] An efficient synthesis of the tricyclic A-B subunit 2 of
      angelmicin B is described. A formal three-component coupling of aldehydes 4 and 6
      with gamma-silylallylborane 7 was employed to assemble the tetrahydrofuranyl core
      of 2, a strategy highlighted by the stereoselective [3 + 2] annulation of
      allylsilanes 5a/5b with aldehyde 4. The efficiency of the [3 + 2] annulation was
      greatly improved by using the allylic benzhydryldimethylsilane 5b compared to the
      allylic phenyldimethylsilane 5a.

PMID- 16288542
TI  - Concatenated catalytic asymmetric allene diboration/allylation/functionalization.
AB  - [reaction: see text] Palladium-catalyzed enantioselective diboration of prochiral
      allenes generates a reactive chiral allylboron intermediate which is a versatile
      reagent for the allylation of carbonyls. Experiments that improve the
      enantioselectivity of this process, examine the substrate scope, and are directed
      toward functionalization of the allylation intermediate are described.

PMID- 16288543
TI  - Synthesis of the C(43)-C(67) fragment of amphidinol 3.
AB  - [reaction: see text] A synthesis of the C(43)-C(67) fragment of amphidinol 3
      (AM3) has been accomplished by a route that features the use of a double
      allylboration reaction for synthesis of 1,5-diol 4b, which serves as a precursor
      to dihydropyran 11.

PMID- 16288544
TI  - Total synthesis of (+)-phomopsolide C by ring-size selective ring-closing
      metathesis/cross-metathesis.
AB  - [reaction: see text]A new strategy for the synthesis of chiral 6-substituted 5,6
      dihydro-5-hydroxypyran-2-ones by ring-size selective ring-closing metathesis
      (RCM) and its application to a short total synthesis of (+)-phomopsolide C are
      described. The key bond-forming reactions in this approach are a chemoselective
      cross-metathesis (CM) and RCM.

PMID- 16288545
TI  - Total stereoselective synthesis of (+)-goniothalesdiol.
AB  - [reaction: see text] The stereoselective synthesis of (+)-goniothalesdiol (1) was
      accomplished in nine steps starting from commercially available (-)-(2S,3S)
      dimethyl D-tartrate (3). The key features were a completely diastereoselective
      reduction of a beta-ketosulfoxide to generate the stereogenic center at C-5 in 7
      and formation of the 2,5-cis-substituted tetrahydrofuran ring in 10 from a
      stereoselective Et(3)SiH/TMSOTf-promoted reductive cyclization/deoxygenation.

PMID- 16288546
TI  - A highly efficient, asymmetric synthesis of benzothiadiazine-substituted tetramic
      acids: potent inhibitors of hepatitis C virus RNA-dependent RNA polymerase.
AB  - [reaction: see text] An efficient two-pot, asymmetric synthesis of
      benzothiadiazine-substituted tetramic acids is reported. Starting from
      commercially available alpha-amino acids or esters, reductive amination followed
      by a novel one-pot amide bond formation/Dieckmann cyclization provided the
      desired products in high yield and optical purity. An analogous solid-phase
      approach to the same targets is also presented. These compounds were found to be
      potent inhibitors of hepatitis C virus RNA-dependent RNA polymerase.

PMID- 16288547
TI  - Divergent synthesis of complex polyketide-like macrolides from a simple polyol
      fragment.
AB  - [structure: see text] Three stereochemically and structurally complex non-natural
      polyketide macrolides have been synthesized from the same simple polyol
      precursor. That this polyol fragment is rapidly available in quantity is key to
      the practicality of these syntheses and allows the targeting of more highly
      complex and "natural product-like" macrolides.

PMID- 16288548
TI  - Facile regiocontrolled synthesis of trialkyl-substituted pyrazines.
AB  - [reaction: see text] Alpha-nitro ketones can be transformed selectively into
      trialkyl-substituted pyrazines via reaction with alpha-amino ketones using octyl
      viologen as an electron-transfer reagent. The new synthetic method, and the
      optimal reaction conditions that allow for the regiochemical control, are
      described.

PMID- 16288550
TI  - Selective 4-arylation of pyridines by a nonmetalloorganic process.
AB  - [reaction: see text] Mild and position-selective nucleophilic 4-arylation of
      pyridines has been accomplished by the use of triflic anhydride N-activation.

PMID- 16288549
TI  - Metal-catalyzed rearrangement of homoallylic ethers to silylmethyl allylic
      silanes in the presence of a Di-tert-butylsilylene source.
AB  - [reaction: see text] In examining the scope of the di-tert-butylsilylene transfer
      to gem-disubstituted alkenes to form silacyclopropanes, we discovered an
      unprecedented reaction of homoallylic ethers. When silylene transfer was
      performed at room temperature or above, two di-tert-butylsilylene units were
      incorporated into the molecule, and complete rearrangement of the carbon backbone
      occurred. This report describes the scope of this unique reaction as well as the
      mechanistic studies conducted that led to a proposed mechanism.

PMID- 16288553
TI  - Why medical students are crucial to the future of research in South Asia.

PMID- 16288554
TI  - Truth, probability, and frameworks.

PMID- 16288555
TI  - Where do people in Nigeria get their contraception?

PMID- 16288556
TI  - Inhibition of EGFR signaling: all mutations are not created equal.

PMID- 16288557
TI  - Response to Amir Attaran.

PMID- 16288558
TI  - Did glycopeptide use in animals result in hospital infections of VRE?

PMID- 16288559
TI  - Power, reliability, and heterogeneous results.

PMID- 16288561
TI  - Placebo: physician, heal thyself.

PMID- 16288560
TI  - The need of a neonatal preparation for Chagas disease.

PMID- 16288562
TI  - The clinical interpretation of research.

PMID- 16288564
TI  - Mental health care and mental health legislation in Pakistan: no mercy for
      losers.

PMID- 16288563
TI  - Genetic research on nicotine dependence will facilitate public health.

PMID- 16288566
TI  - Restoring retinal function in a mouse model of hereditary blindness.

PMID- 16288567
TI  - Mitochondrial DNA mutations in cancer.

PMID- 16288572
TI  - [Quality management in heart failure].

PMID- 16288573
TI  - [Quality management in patients with heart failure inside an Internal Medicine
      Department].
AB  - OBJECTIVE: To evaluate the quality management of Heart failure within an Internal
      Medicine Department, based in quality criteria settled in ACOVE study. METHODS:
      Retrospective study reporting 267 patients admitted to our Internal Medicine
      Department with a diagnosis of heart failure (from January 2001 to January 2001).
      We applied ACOVE protocol to evaluate quality of management assigning a positive
      numerical score to every accomplished section and a negative score to those
      sections that were not carried out. RESULTS: Two hundred and sixty seven patients
      and their clinical records were evaluated (Mean age 76 +/- 9 years, male 50%).
      They had a mean score of 6.72 +/- 1.33 points. Heart failure etiology was
      determined in 82% (33% ischemic heart failure, 30% hypertensive heart disease,
      12% valvulopathy and 7% others). ACE-Inhibitors/ARA II were used in 66% of
      patients, with poor utilization of beta-blockers (16%), calcium channel blockers
      (7%) and class I antiarrhythmic drugs (1%). 94% of patients had written
      instructions about manage of their disease. Only 36% of patients had an
      echocardiography study. In patients with atrial fibrillation, 19% were treated
      with oral anticoagulants and 26% with anti-platelet drugs. In-hospital mortality
      rate was 4%. We could not meet differences among different physicians and their
      gender in department of Internal Medicine treating for heart failure, however the
      score of patients older 70 years was 6.5 +/- 1.38 points while score in younger
      to years was 7.15 +/- 1.17 points (p = 0.011). CONCLUSIONS: Management of heart
      failure in our department of Internal Medicine is acceptable. However, there are
      several points in which improvement could be reached, much as to increase the
      utilization of ACE inhibitors and beta-blockers in handling of heart failure and
      to rise the are of echocardiography in the evaluation of these patients.
      Moreover, older patients showed a lower quality level that could be improved.

PMID- 16288574
TI  - [Mini Nutritional Assessment (MNA) test as a tool of nutritional evaluation in
      hospitalized patients].
AB  - OBJECTIVE: The objective of the study was to identified the prevalence of
      malnutrition in come patients with MNA (Mini Nutritional Assessment) test as a
      clinical tool. METHODS: A total of 145 patients were studied in Hospital del Rio
      Hortega (Valladolid), from mars of 2000 till may of 2002. In all patients a MNA
      test, an anthropometric and biochemical evaluation were performed. RESULTS: Mean
      age was 57.44 +/- 18.06 years, weight 63.5 +/- 13.7 kg and body mass index 23.4
      +/- 4.9 kg/m2. The studied population were 48.6% haematological tumours and other
      tumours, opposite to the rest of the patients who were presenting cerebro
      vascular accidents 2.1%, respiratory problems or infections 16.8%, renal failure
      3.5% and neurological diseases or processes of dementia in minor proportion 2.9%.
      Patients were divided in two groups, malnutrition MNA < 17 (n = 99) (group I) and
      risk of malnutrition MNA = 17 (n = 43) (group II). The malnutrition prevalence
      was 68.2% (group I) and risk of malnutrition 29.6% (group II) with test MNA. In
      biochemical evaluation the malnutrition group I had low levels of albumin (2.9 +/
      0.7 g/dl vs 3.41 +/- 2.71 g/dl; p < 0.05), prealbumin (14.9 +/- 6.2 g/dl vs 17.6
      +/- 8.1 g/dl; p < 0.05) and transferrin (152.2 +/- 54.9 g/dl vs 189.9 +/- 32.6
      g/dl; p < 0.05. Arm muscular circumference and arm circumference had values under
      average in patients with malnutrition. On having analyzed the different
      paragraphs of the test MNA between both groups, it was observed since in the
      group of undernourished patients the punctuation he was below the average in all
      the paragraphs. CONCLUSIONS: The risk of malnutrition in hospital was frequent,
      detected by MNA test.

PMID- 16288575
TI  - [Splanchnic remodeling secondary to experimental prehepatic portal hypertension].
AB  - OBJECTIVE: Portal hypertension as an inducer of intestinal inflammatory response
      would cause epithelial and splanchnic vascular remodeling in the long-term. This
      experimental study was carried out to verify this hypothesis. METHOD: Structural
      alterations characteristic of intestinal epithelial and mesenteric vascular
      remodeling, the density of goblet cells and the diameter of mesenteric vein
      branches were studied, respectively, in rats with partial portal vein ligation in
      the short (1 month) and long-term (1 year). RESULTS: Hyperplasia of goblet cells
      in the small intestine (duodenum, jejunum, ileum) is maximum after 1 year of
      evolution of the portal hypertension and is associated with dilatation of the
      distal branches (3rd and 4th order) of the superior mesenteric vein. CONCLUSION:
      Long-term splanchnic remodeling in experimental portal hypertension suggests the
      existence of a chronic inflammatory process in this clinical condition.

PMID- 16288576
TI  - [Relation between intake of omega 3 fatty acids and CD4 count in patients with
      HIV infection: a transversal study].
AB  - OBJECTIVES: Polyunsaturated fatty acids are immunomodulatory agents. These agents
      could develop a main role in patients with HIV infection. The aim of our study
      was to analyse the relation between polyunsaturated fatty acid intake and CD4
      count in HIV infected patients. PATIENTS AND METHODS: Forty patients with HIV
      infections were enrolled. In all patients, the next variables were recorded; age,
      sex, drugs, anthropometric evaluation (weight, height, tricipital skinfold,
      midarm circumference, body mass index) and a biochemical evaluation (albumin,
      prealbumin, trasferrin, total proteins, total lymphocytes and CD4 count). A 3 day
      dietary intake questionnaire was performed, too. RESULTS: The mean age was (24
      males and 16 females) 37.6 +/- 9.4 years, mean weight 65.6 +/- 12.2 kg and body
      mass index 23.2 +/- 3.25. Anthropometric evaluation showed a mean tricipital
      skinfold of 15.1 +/- 5.3 mm, midarm circumference 27.5 +/- 3.1 cm. Caloric intake
      and macronutrient distribution were normal (carbohydrates 48%, proteins 18% and
      lipids 34%). Dietary intake of polyunsaturated fatty acids was omega 3 (1.22 +/-
      3.1 g/day) and omega 9 (31.5 +/- 11 g/day). Multivariante analysis, with CD4
      count as a dependent variable, showed omega 3 intake as a independent variable (F
      = 6.2; p < 0.05), with an increase of 32 (IC95%: 9.86-52.14) CD4+ (count/uL) with
      each 1 g of omega 3 dietary intake adjusted by age, sex, and drugs. CONCLUSION:
      In patients with HIV infection, dietary intake of omega 3 fatty acids increase
      CD4 count.

PMID- 16288577
TI  - [Cardiac tamponade caused by hydatid pericarditis].
AB  - We present the case of a woman with no previous clinical history of disease, that
      debuted with acute heart failure with symptoms of cardiac tamponade from hydatic
      pericarditis as a result of a fistula across the diaphragm secondary to a
      hydatidic cyst rupture in the liver. Cardiac hydatidosis is rare with an
      incidence in some series between 0.2-2% in humans infested with Echinococcus,
      affectation of the pericardia being rare. For this reason we present a revision
      of its pathogenesis, clinical presentation, diagnosis and recommended treatment.

PMID- 16288579
TI  - [Addison's disease: the challenge of an early diagnosis].
AB  - Addison's disease is a set of symptoms which is produced due to the destruction
      of the suprarenal cortex, of a mainly autoimmune origin, on account of the
      presence of antibodies which attack it. This destruction takes place in a
      generally slow manner, causing symptoms to appear in an insidious way, added to
      the fact that these symptoms tend to be unspecific. Therefore it is easy to
      understand that its diagnosis at an early stage will be very difficult and is
      often interpreted as another disease. It is only when the deficit is important
      and adrenal crisis develop that we can reach the right diagnosis in a situation
      where the death risk is considerably high. We presented a clinical case as an
      example of what has been described previously. After several months of
      progressively deteriorating symptoms and several visits to different medical
      units, the patient is diagnosed as having an adrenal crisis and is immediately
      admitted to the intensive care unit.

PMID- 16288578
TI  - [Idiopathic pulmonary artery aneurysm: report of a case and review of the
      literature].
AB  - Woman of 63 years old with essential arterial hypertension, essential trembling
      and chronic venous insufficiency of inferior members; she came to the Internal
      Medicine outpatients department because of her chronic venous insufficiency,
      objectifying in the physical examination a systolic heart murmur II/VI in the
      left sternal border and many signs of chronic venous insufficiency in the
      inferior members. In the chest radiograph was found as an accidental finding, a
      properly delimited vascular image in the left upper mediastino, for this reason
      there were later realized diverse complementary examinations gradually more
      aggressive, that included a pulmonary angiography which revealed the presence of
      an aneurysmatic dilatation in the common and left pulmonary arteries. With these
      findings, the patient was undergoing a surgical operation, in which was realized
      a partial resection and folder to the common and left pulmonary arteries to
      reduce diameter to 2-3 centimetres, with a post-operative period without
      complications and staying without symptoms after the surgery.

PMID- 16288580
TI  - [Focal peritonitis as a form of clinical presentation of listeriosis].
AB  - Infections by germs of Listeria genus can occur sporadically or in epidemic
      outbreaks and have different clinical presentations. Abdominal origin is very
      unusual among them, especially in no immunocompromised patients or without
      concurrent liver illness. We present a young healthy man who is lacking in
      underlying diseases, suffering from focal peritonitis caused by Listeria
      monocytogenes. The patient had to be operated on, requiring immediate colectomy
      and evacuation of a retroperitoneal abscess. The postoperative evolution was
      favorable under antibiotic treatment with amoxicillin and clavulanic acid during
      3 weeks. The clinical-epidemiological and therapeutic aspects of listeriosis are
      analysed in the discussion, giving special attention to abdominal infective
      episodes.

PMID- 16288581
TI  - [Management of diabetes in hospitalized patients].

PMID- 16288582
TI  - [Escherichia coli septic arthritis in a woman with gout].

PMID- 16288583
TI  - The determinants of quality in procedural rural medical care.
AB  - INTRODUCTION: A substantial proportion of health services for rural Australians
      is provided in rural health facilities by rurally based generalist health
      professionals. These services include procedural care within smaller rural
      hospitals, where teams of health professionals--medical practitioners, nurses and
      other support staff--work in teams to deliver a range of procedural services,
      both elective and urgent, that reduce the need for rural people to travel to
      major centres. Recent debate over the training of rural medical practitioners has
      focused on whether or not they need to provide procedural services, because
      current health service management policy appears to support the rationalisation
      and centralisation of service delivery in larger centres to contain costs and
      ensure high quality. Hence there is an assumption, without much evidence, that
      the quality of care in rural hospitals is lower than that provided in larger
      urban hospitals, although there is little agreement on just what aspects of care
      should be measured to indicate its quality. This article reports an exploration
      of multiple perspectives on what constitutes quality of care in rural procedural
      medical practice, as part of a broader study of the quality of care of a series
      of real clinical cases. METHODS: During the collection of a series of 91
      individual patient cases involving anaesthetic, obstetric or surgical procedures
      conducted in small rural hospitals, interviews were conducted with several
      participants in each case: the rural doctors; rural nurses; the rural patients;
      and family members of those patients. In addition to issues pertaining to each
      case, interviews explored the perspectives of individuals in each group on the
      broader question of what constitutes quality of care in a general sense. Their
      comments were subjected to qualitative thematic analysis using Atlas.ti software
      (Muhr T, ATLAS.ti Scientific Software Development; Berlin, Germany). In order to
      consider how to measure rural health care, the thematic comments were then
      applied to a Donabedian structure/process/outcome model. RESULTS: The different
      groups produced different views on what might determine the quality of health
      care in rural hospitals. The health professionals tended to focus on technical
      aspects of care, although the doctors and nurses had some different emphases,
      while the patients and their families were more concerned with access,
      interpersonal communication, convenience and cost. These themes appeared to be
      consistent with previous literature from general healthcare settings. A list of
      indicators is suggested for measuring the quality of rural health care.
      CONCLUSION: This study has improved understanding of the differing views held by
      rural health professionals and rural patients in thinking about the quality of
      care provided in rural hospitals. Consideration of the quality of procedural
      rural medical care should include the needs and expectations of those living and
      working in a smaller, more familiar environment. This has implications for health
      planners, and suggests that there is a continuing need for rural health
      professionals to be trained to provide procedural medical services in rural
      hospitals, and for rural hospitals to be maintained at a standard necessary to
      support quality service provision.

PMID- 16288585
TI  - Mechanical circulatory support in children: extracorporeal membrane oxygenation
      and ventricular assist devices.

PMID- 16288587
TI  - StarClose femoral arteriotomy closure device: an advance in arterial closure.
AB  - Millions of femoral arterial punctures are performed annually worldwide for the
      diagnosis and treatment of cardiovascular disease. Traditionally, hemostasis
      following arterial sheath removal has employed compression techniques but more
      recently, a number of arteriotomy closure devices have become available, none of
      which have been shown to produce an outcome superior to the standard technique of
      compression. The authors investigated a novel device, which utilizes a nitinol
      clip that gathers the artery from the outside producing a purse-string-like seal,
      with very promising results. The authors feel that this device has great
      potential, may impact significantly on the closure of arteriotomy sites and may
      also find application in other aspects of procedural medicine.

PMID- 16288588
TI  - Sacral nerve stimulation: Interstim therapy.
AB  - Sacral nerve stimulation is a young but promising technique in the treatment of
      chronic voiding dysfunctions. Electrical stimulation of the S3 nerve--using a
      pacemaker device--is able to treat a wide range of pelvic floor dysfunctions.
      This article gives a brief review on the indications, mechanisms of action and
      possible complications of this technique. Furthermore, new evolutions in the
      domain of sacral nerve modulation are discussed.

PMID- 16288589
TI  - The use of wireless capsule endoscopy in clinical diagnostic gastroenterology.
AB  - This profile describes a new wireless video endoscopy device designed to image
      previously inaccessible areas of the gastrointestinal tract with unprecedented
      precision and clarity. This PillCam technology involves a disposable, ingestible
      camera that transmits more than 50,000 digital images of the small bowel to
      personal computer software. The wireless capsule endoscopy technology supplements
      and is rapidly replacing standard small bowel imaging techniques, and its use has
      revolutionized conventional ideas about the small bowel's role in many conditions
      such as Crohn's disease and occult blood loss. In addition to the small bowel
      device, an esophageal adaptation was released in January 2005. This capsule
      technology anticipates exponential growth in both diagnostic and possible
      therapeutic dimensions in the future.

PMID- 16288590
TI  - Anti-infective therapy with an Er:YAG laser: influence on peri-implant healing.
AB  - In addition to conventional treatment modalities (mechanical and chemical), the
      use of lasers has been increasingly proposed for the treatment of periodontal and
      peri-implant infections (i.e., cleaning and detoxification of implant surfaces).
      Preliminary results from basic studies have pointed to the high potential of the
      Erbium-doped: Yttrium, Aluminum and Garnet (Er:YAG) laser. Furthermore,
      preliminary clinical data indicate that treatment with this kind of laser may
      positively influence peri-implant healing. The aim of this research update is to
      evaluate, based on the currently available evidence, the use of an Er:YAG laser
      for the treatment of peri-implant infections and to indicate its potential as a
      new treatment modality.

PMID- 16288591
TI  - Microdialysis of the bowel: the possibility of monitoring intestinal ischemia.
AB  - Assessment of the intestinal circulation in a clinical setting still presents a
      significant diagnostic challenge. In patients suspected of having intestinal
      ischemia pre- or postoperatively, there is no clinically relevant marker which
      can determine whether the bowel is suffering from lack of oxygen or not.
      Microdialysis is a microinvasive technique that makes it possible to continuously
      detect tissue-specific metabolic changes. Recently, it has been demonstrated that
      intestinal ischemia can be detected and monitored continuously by the use of a
      microdialysis catheter placed in the proximity of the ischemic bowel. This review
      summarizes the clinical dilemma of intestinal ischemia and the latest
      experimental results using the microdialysis technique to detect critical
      perfusion in the small intestine. The possibility of using microdialysis in a
      clinical setting is outlined with the perspective of using it as a pre- or
      postoperative monitoring tool in relevant patients.

PMID- 16288592
TI  - Hydro-Jet technology in urologic surgery.
AB  - Hydro-Jet technology utilizes an extremely thin, high-pressure stream of water.
      This technology has been routinely used in industry as a cutting tool for
      different materials such as metal, ceramic, wood and glass. Recently, Hydro-Jet
      technology has been used for dissection and resection during open and
      laparoscopic surgical procedures. A high-pressure jet of water allows selective
      dissection and isolation of vital structures such as blood vessels and nerves.
      This has resulted in improved dissection and decreased complication rate in
      recent experimental and clinical studies. This technology has been successfully
      applied during open and laparoscopic partial nephrectomy, cholecystecomy and
      retroperitoneal lymphadenectomy.

PMID- 16288593
TI  - The potential for the use of nanofeaturing in medical devices.
AB  - This review looks at potential developments in medical devices which may be based
      upon nanofeaturing implant and tissue engineering scaffolds, and describes the
      basic science upon which such expectations are based.

PMID- 16288594
TI  - Bioactive composite materials for tissue engineering scaffolds.
AB  - Synthetic bioactive and bioresorbable composite materials are becoming
      increasingly important as scaffolds for tissue engineering. Next-generation
      biomaterials should combine bioactive and bioresorbable properties to activate in
      vivo mechanisms of tissue regeneration, stimulating the body to heal itself and
      leading to replacement of the scaffold by the regenerating tissue. Certain
      bioactive ceramics such as tricalcium phosphate and hydroxyapatite as well as
      bioactive glasses, such as 45S5 Bioglass, react with physiologic fluids to form
      tenacious bonds with hard (and in some cases soft) tissue. However, these
      bioactive materials are relatively stiff, brittle and difficult to form into
      complex shapes. Conversely, synthetic bioresorbable polymers are easily
      fabricated into complex structures, yet they are too weak to meet the demands of
      surgery and the in vivo physiologic environment. Composites of tailored physical,
      biologic and mechanical properties as well as predictable degradation behavior
      can be produced combining bioresorbable polymers and bioactive inorganic phases.
      This review covers recent international research presenting the state-of-the-art
      development of these composite systems in terms of material constituents,
      fabrication technologies, structural and bioactive properties, as well as in
      vitro and in vivo characteristics for applications in tissue engineering and
      tissue regeneration. These materials may represent the effective optimal solution
      for tailored tissue engineering scaffolds, making tissue engineering a realistic
      clinical alternative in the near future.

PMID- 16288595
TI  - Preventing the transmission of pathogenic microbes during anesthesia.
AB  - During anesthesia, a breathing system may be used for more than one patient. Any
      microbes expelled by one patient, whether gasborne in the form of droplets or
      liquidborne in sputum, should be prevented from entering the breathing system.
      Breathing system filters are intended to reduce the risk of cross infection
      during anesthesia and intensive care from these routes. The Medicines and
      Healthcare products Regulatory Agency published a report in 2004 that included
      data on the gasborne filtration performance of 104 different filters available on
      the UK market. A wide range in filtration performance was found. Filters intended
      for use with pediatric patients do not appear to offer the same level of
      protection as those intended for use with adult patients, despite the lower flow
      used to challenge these filters. Recent government initiatives to reduce the
      prevalence of tuberculosis and hepatitis C in England have again focused interest
      on the ability of filters to reduce the risk of cross infection from these
      particular microbes arising from patients who may not be aware that they are
      harboring the disease. Currently, there are no requirements for the level of
      filtration that breathing system filters have to provide, either in standards or
      from professional bodies.

PMID- 16288596
TI  - Bladder neck pubovaginal slings.
AB  - Over the past 30 years, the pubovaginal sling has surpassed retropubic and
      transvaginal suspensions as the most common surgical operation for correcting
      stress urinary incontinence. This resurgence has been due in part to innovative
      technological advances that have shortened operative times and expedited
      postoperative recovery. The introduction of novel allografts, xenografts and
      synthetic materials has also been accompanied by unique complications, previously
      not encountered with autologous materials. The aim of this review is to compare
      the available sling materials in the context of biocompatibility and efficacy.

PMID- 16288597
TI  - Inflatable penile prostheses for the treatment of erectile dysfunction.
AB  - Male erectile dysfunction is a common medical condition. Recent advances in our
      understanding of corpora cavernosa physiology have resulted in three effective
      oral medications (sildenafil, vardenafil and tadalafil--all phosphodiesterase
      type 5 inhibitors), which can effectively treat many men with erectile
      dysfunction. However, a large number of men are not adequately treated by these
      medications due to their cost, side effects, contraindications or lack of a
      satisfactory erectile response. For men who do not respond to less invasive
      therapy, an inflatable penile prosthesis can provide an excellent alternative.
      This article will review and critique the currently available inflatable penile
      prostheses in the treatment of erectile dysfunction.

PMID- 16288598
TI  - Current state and future development of intracranial neuroendoscopic surgery.
AB  - Since the introduction of the modern, smaller endoscopes in the 1960s,
      neuroendoscopy has become an expanding field of neurosurgery. Neuroendoscopy
      reflects the tendency of modern neurosurgery to aim towards minimalism; that is,
      access and visualization through the narrowest practical corridor and maximum
      effective action at the target point with minimal disruption of normal tissue.
      Transventricular neuroendoscopy allows the treatment of several pathologies
      inside the ventricular system, such as obstructive hydrocephalus and intra
      /paraventricular tumors or cysts, often avoiding the implantation of extracranial
      shunts or more invasive craniotomic approaches. Endoscopic endonasal
      transphenoidal surgery allows the treatment of pathologies of the sellar and
      parasellar region, with the advantage of a wider vision of the surgical field,
      less traumatism of the nasal structures, greater facility in the treatment of
      possible recurrences and reduced complications. However, an endoscope may be used
      to assist microsurgery in virtually any kind of neurosurgical procedures
      (endoscope-assisted microsurgery), particularly in aneurysm and tumor surgery.
      Basic principles of optical imaging and the physics of optic fibers are
      discussed, focusing on the neuroendoscope. The three main chapters of
      neuroendoscopy (transventricular, endonasal transphenoidal and endoscope-assisted
      microsurgery) are reviewed, concerning operative instruments, surgical
      procedures, main indications and results.

PMID- 16288599
TI  - Unique structure of Ascaris suum b5-type cytochrome: an additional alpha-helix
      and positively charged residues on the surface domain interact with redox
      partners.
AB  - Cytochrome b5 of the body wall of adult Ascaris suum, a porcine parasitic
      nematode, is a soluble protein that lacks a C-terminal membrane-anchoring domain,
      but possesses an N-terminal pre-sequence of 30 amino acids. During the maturation
      of cytochrome b5, the N-terminal pre-sequence is proteolytically cleaved to form
      the mature protein of 82 amino acid residues. A. suum cytochrome b5 is a basic
      protein containing more lysine residues and exhibiting a higher midpoint redox
      potential than its mammalian counterparts. We developed an expression system for
      the production of the recombinant nematode cytochrome b5, which is chemically and
      functionally identical with the native protein. Using this recombinant protein,
      we have determined the X-ray crystal structure of A. suum cytochrome b5 at 1.8 A
      (1 A=0.1 nm) resolution, and we have shown that this protein is involved in the
      reduction of nematode body-wall metmyoglobin. The crystal structure of A. suum
      cytochrome b5 consists of six alpha-helices and five beta-strands. It differs
      from its mammalian counterparts by having a head-to-tail disulphide bridge, as
      well as a four-residue insertion in the vicinity of the sixth ligating histidine,
      which forms an additional alpha-helix, alpha4A, between helices alpha4 and
      alpha5. A. suum cytochrome b5 exists predominantly as a haem-orientation B
      isomer. Furthermore, the haem plane is rotated approx. 80 degrees relative to the
      axis formed by haem-Fe and N atoms of the two histidine residues that are ligated
      to haem-Fe. The charge distribution around the haem crevice of A. suum cytochrome
      b5 is remarkably different from that of mammalian cytochrome b5 in that the
      nematode protein bears positively charged lysine residues surrounding the haem
      crevice. Using immunohistochemistry, we found that A. suum cytochrome b5 is
      present in the nematode hypodermis. Based on this histochemical and structural
      information, the physiological function of A. suum cytochrome b5 and its
      interaction with nematode metmyoglobin can be hypothesized.

PMID- 16288600
TI  - A Toxoplasma gondii phosphoinositide phospholipase C (TgPI-PLC) with high
      affinity for phosphatidylinositol.
AB  - The Toxoplasma gondii phosphoinositide-specific phospholipase C gene (TgPI-PLC)
      was cloned, sequenced and expressed in Escherichia coli and its enzymatic
      characteristics were investigated. TgPI-PLC is present in the genome as a single
      copy gene consisting of 22 exons interrupted by 21 introns, and encodes a
      polypeptide of 1097 amino acids with a predicted molecular mass of 121 kDa. In
      addition to the conserved catalytic X and Y domains, TgPI-PLC contains an
      apparent N-terminal PH domain, an EF hand motif and a C-terminal C2 domain. When
      compared with mammalian delta-type PI-PLC, TgPI-PLC has an additional extended N
      terminus and two insertions in the region between the X and Y domains, with a 31
      35% identity over the whole sequence. Recombinant TgPI-PLC, as well as the native
      enzyme obtained from crude membrane extracts of the parasite, was more active
      with phosphatidylinositol than with phosphatidylinositol 4,5-bisphosphate as
      substrate. Indirect immunofluorescence analysis using an affinity-purified
      antibody against TgPI-PLC revealed that this enzyme localizes in the plasma
      membrane of the parasites.

PMID- 16288602
TI  - The central retinal artery and regression of the hyaloid artery in perinatal
      cattle.
AB  - The arterial supply to the retina and lens of 10 fetal, 10 neonatal and four
      adult Zavot-bred cattle of both sexes was studied macroscopically and by
      stereoscopic microscopy by means of vascular perfusion with latex, giving special
      emphasis on the hyaloid artery. The central retinal artery ramified in four major
      retinal arterioles, which formed a compact network throughout the retina
      (holangiotic or euangiotic pattern). The hyaloid artery was patent in all fetal
      stages and extended through the vitreous cavity of the eye to the caudal surface
      of the capsule of the lens. Atrophy of the hyaloid artery began immediately after
      birth and was completed on day 17 after parturition. No remnant of the hyaloid
      artery in the vitreous cavity was observed in the adult cattle examined at
      stereoscopic microscopic level.

PMID- 16288603
TI  - The presence of megamitochondria in the ellipsoid of photoreceptor inner segment
      of the zebrafish retina.
AB  - Although the megamitochondria (MM) were localized in various pathological
      conditions, normal retina of some mammalian species was reported to include MM
      for various physiological roles. However, it was not clearly confirmed whether
      the MM is present in the retina of lower vertebrate as well. In this study, we
      tried to show the presence of the MM in the zebrafish retina using electron
      microscopic technique. In all the photoreceptors including rods, cones and double
      cones of the zebrafish retina, MM were observed in the ellipsoid of inner
      segment. In the photoreceptor epllipsoid of the zebrafish retina, the
      mitochondria located in the central portion of the ellipsoid had a highly
      electron-dense matrix, which were accompanied by the mitochondria with electron
      lucent matrix in the apical portion of the ellipsoid. The presence of MM was more
      clearly discernable in the rods, which were localized under the double cones.
      This finding is somewhat different from those observed in the previous studies
      because MM were localized in the inner segment of cones, but were not in those of
      rods in the case of mammalian retina. Although the exact physiological meaning
      for the presence of MM in some vertebrate species should be further studied, the
      present study could show that the MM in the ellipsoid of the retinal
      photoreceptors was not only restricted in some mammalian species.

PMID- 16288601
TI  - Effects of insulin and cytosolic redox state on glucose production pathways in
      the isolated perfused mouse liver measured by integrated 2H and 13C NMR.
AB  - A great deal is known about hepatic glucose production and its response to a
      variety of factors such as redox state, substrate supply and hormonal control,
      but the effects of these parameters on the flux through biochemical pathways
      which integrate to control glucose production are less clear. A combination of
      13C and [2H]water tracers and NMR isotopomer analysis were used to investigate
      metabolic fluxes in response to altered cytosolic redox state and insulin. In
      livers isolated from fed mice and perfused with a mixture of substrates including
      lactate/pyruvate (10:1, w/w), hepatic glucose production had substantial
      contributions from glycogen, PEP (phosphoenolpyruvate) and glycerol. Inversion of
      the lactate/pyruvate ratio (1:10, w/w) resulted in a surprising decrease in the
      contribution from glycogen and an increase in that from PEP to glucose
      production. A change in the lactate/pyruvate ratio from 10:1 to 1:10 also
      stimulated flux through the tricarboxylic acid cycle (2-fold), while leaving
      oxygen consumption and overall glucose output unchanged. When lactate and
      pyruvate were eliminated from the perfusion medium, both gluconeogenesis and
      tricarboxylic-acid-cycle flux were dramatically lower. Insulin lowered glucose
      production by inhibiting glycogenolysis at both low and high doses, but only at
      high levels of insulin did gluconeogenesis or tricarboxylic-acid-cycle flux tend
      towards lower values (P<0.1). Our data demonstrate that, in the isolated mouse
      liver, substrate availability and cellular redox state have a dramatic impact on
      liver metabolism in both the tricarboxylic acid cycle and gluconeogenesis. The
      tight correlation of these two pathways under multiple conditions suggest that
      interventions which increase or decrease hepatic tricarboxylic-acid-cycle flux
      will have a concomitant effect on gluconeogenesis and vice versa.

PMID- 16288604
TI  - Morphological and immunocytochemical investigations on mast cells in porcine
      ureter.
AB  - Morphological, morphometric, histochemical and immunocytochemical investigations
      on mast cells, located in the wall of ureter of 8 months aged pigs were
      performed. Mast cells were found in all three layers of ureteral wall, but their
      distribution was irregular and the number unequal. It was established that alcian
      blue (AB)-positive mast cells were significantly more than toluidine blue (TB)
      positive mast cells. A statistically significant smaller number of both AB and TB
      stained mast cells were observed in the tunica mucosa. The largest number of mast
      cells was found in the tunica muscularis. In the adventitia, mast cells were
      higher in number in the main connective tissue than in the connective tissue near
      the blood vessels. Mast cells stained with TB showed variably expressed gamma
      metachromasia, which was best visible in those situated in the lamina propria of
      the mucosa. The prevailing parts of mast cells, however, were AB-positive after
      AB-safranin staining. This was mostly found in mast cells of the tunica
      muscularis and in mast cells of perivascular location in the tunica adventitia.
      Immunocytochemically, mast cells were found to be positive for histamine and
      vasoactive intestinal polypeptide in the muscle coat, and to histamine in the
      adventitia, as well. On the basis of obtained results it was presumed that the
      mast cells in porcine ureter most probably took part not only in keeping of local
      homeostasis, but played also an important role of mobility of smooth muscle cells
      in the middle layer of ureter on one hand, and, on the other, in the adventitial
      blood vessels.

PMID- 16288605
TI  - Morphological features of the luminal surface of the magnum in the sexually
      immature ostrich (Struthio camelus).
AB  - Summary Observations were made, using scanning electron microscopy, of the
      surface features of the magnum in the immature ostrich during periods of ovarian
      inactivity, activity and regression. In birds with inactive ovaries the luminal
      surface of the magnum was lined with non-ciliated cells, which were densely
      covered by microvilli. In contrast, the magnum in birds with active ovaries was
      composed of ciliated and non-ciliated cells. The distribution of ciliated cells
      was not uniform, with clumps of cilia occurring next to non-ciliated areas.
      Samples collected from birds with regressing ovaries, during periods of
      decreasing daylength, revealed that the magnum was undergoing involution. The
      deciliation of ciliated cells and the presence of short microvilli on non
      ciliated cells characterized magnal regression. These results suggest that
      ovarian activity and changes in daylength have a profound effect on the surface
      features of the magnum in the immature ostrich.

PMID- 16288606
TI  - Three-dimensional vasculature of the bovine liver.
AB  - To clarify anatomical distribution of Fasciola infection, the vascular and ductal
      architectures of the liver were studied by means of corrosion cast technique
      using synthetic resin. The arteria hepatica propria (AP) passes as the arteria
      gastroduodenalis (AG); AP becomes the left trunk after the porta hepatis; AP
      passes on the right side of vena porta communis (VPC) and projects AG while
      curving in a U-shape below the portal vein. Hepatic veins located between the
      vena hepatica media (HM) and vena hepatica dextra (HD) varied widely among
      specimens and were irregular, including the vena hepatica dorso-lateralis
      sinistra (Hds), vena hepatica dorso-lateralis dextra (Hdd), vena hepatica lobi
      caudati (Hlc), venae hepaticae processus caudati (Hpc), venae hepaticae processus
      papillaris (Hpp), and the hepatic vein to the dorsal intermediate part, which
      directly or indirectly drained into the vena cava caudalis. The courses of the
      bovine hepatic veins were markedly diverse, and anastomoses between vena hepatica
      sinistra (HS) and Hds were observed in about a half of the livers. The portal
      vein entered the liver as VPC slightly above the centre of the right lobe on the
      visceral surface. The intermediate or transverse part [pars transversa trunci
      sinistri (PTS)] of truncus sinister (TS), which extends from the entry of the
      portal vein into the left lobe of the liver, was slightly arched downward [pars
      umbilicalis trunci sinistri (PUS)]. The portal vein further arched from the
      distal end of TS to the umbilical vein and ran towards the inter-lobar incision
      between the left lobe and quadrate lobe. Based on these branches, hepatic
      segments were determined as 13 or 14 areas. A total of 15 bile ducts were derived
      from various lobes. The hepatic duct was about 2.6-6 cm long from the confluence
      of the right and left hepatic ducts to the division of the cystic duct and the
      common hepatic duct.

PMID- 16288607
TI  - Prenatal development of the caudal vena cava in mammals: review of the different
      theories with special reference to the dog.
AB  - Several items of the development of the caudal vena cava in domestic animals are
      still controversial. In particular, the origin of the lumbar segment of the
      caudal vena cava is equivocally described. According to different theories it
      originates from the right-sided supracardinal, caudal cardinal, sacrocardinal,
      lateral sympathetic or subcardinal veins. In this review, all five theories are
      compared with each other and discussed in the light of anatomical variations
      observed in eight dogs. Species-specific diversity, erratic observations because
      of technical artefacts, and biased interpretation of the original data are three
      major reasons for the dissimilarity between the five theories, but they cannot
      explain all differences. Further studies by using modern techniques such as
      microvascular corrosion casting and non-invasive three-dimensional
      microtomography are necessary to better understand the normal development and to
      explain the variations in domestic animal species.

PMID- 16288608
TI  - Immunohistochemical study on the distribution and relative frequency of endocrine
      cells in the stomach of the Malayan Pangolin, Manis javanica.
AB  - The distribution and relative frequency of six kinds of endocrine cells in the
      stomach of the Malayan pangolin, Manis javanica were studied
      immunohistochemically using the avidin-biotin-peroxidase complex method. The
      stomach of the pangolin has three regions of mucous gland, one oxyntic gland and
      one pyloric gland. Cells immunoreactive for chromogranin, serotonin,
      somatostatin, BPP and glucagon were detected in all of the gastric glands, while
      gastrin-immunoreactive cells were found in the entire gastric gland except for
      the oxyntic gland. The distribution pattern of endocrine cells in the mucous
      gland and pyloric gland was mainly from the middle to apical portions of the
      glands. The endocrine cells were rare or not detected in the basal portion of all
      of the mucous glands and pyloric gland, but they were also found in the basal
      portion of the oxyntic gland. The distribution pattern of the endocrine cells in
      the mucous and pyloric glands suggested that this position facilitates a quick
      response to the luminal ingesta. The wide distribution of gastrin-immunoreactive
      cells in all of the mucous glands and pyloric gland was the most remarkable
      finding. This distribution suggests a major function of gastrin-immunoreactive
      cells for the digestive process in the Malayan pangolin stomach.

PMID- 16288609
TI  - Scanning electron microscopy of the choroid plexus of the lateral ventricle of
      the horse.
AB  - The present study examined the ultrastructure of the choroid plexus of the
      lateral ventricle of the horse. The material was fixed in 2.5% glutaraldehyde in
      0.1 m sodium phosphate buffer, pH 7.3, processed and analysed by scanning
      electron microscopy. The choroid plexus was characterized by regions with a
      predominance of villi, which resembled finger-like projections or bunches of
      grapes, and others where straight and uniform folds predominated. Epithelial
      cells projected into the ventricle and large amounts of cilia and microvilli were
      observed on their surface. The choroid glomus corresponded to a dilatation of the
      choroid plexus and was characterized by blood vessels of different calibres
      surrounded by connective tissue.

PMID- 16288611
TI  - Bullying in the workplace.

PMID- 16288612
TI  - Association between early postoperative coagulation activation and peri-operative
      myocardial ischaemia in patients undergoing vascular surgery.
AB  - We investigated the association of peri-operative myocardial ischaemia with
      activation of coagulation and endogenous fibrinolysis in patients undergoing
      vascular surgery. In 50 patients, continuous Holter monitoring was performed to
      assess peri-operative myocardial ischaemia and 12-lead electrocardiography was
      recorded preoperatively and 72 h postoperatively to assess myocardial infarction.
      Serial blood samples were drawn peri-operatively to determine the concentrations
      of fibrin monomers (for activation of coagulation), D-dimer (for endogenous
      fibrinolysis) and cardiac troponin T and I. Patients with myocardial ischaemia
      showed higher concentrations of fibrin monomers at 48 h, and higher
      concentrations of d-dimer preoperatively and at 24 and 48 h postoperatively. In
      patients with peri-operative myocardial ischaemia, strong positive correlations
      were observed between fibrin monomer and D-dimer concentrations at 15 min and 4 h
      postoperatively, and cardiac troponins at 15 min and at 4, 24, 48 and 72 h
      postoperatively. Early postoperative activation of coagulation and fibrinolysis
      is associated with peri-operative myocardial cell damage among patients who are
      at risk for, or have a history of, coronary artery disease plus peri-operative
      myocardial ischaemia.

PMID- 16288613
TI  - Comparison of the effects of intrathecal morphine and pethidine on shivering
      after Caesarean delivery under combined-spinal epidural anaesthesia.
AB  - We performed a prospective, randomised, double blind study to compare the
      antishivering effect of morphine and pethidine when added to intrathecal
      hyperbaric bupivacaine during elective Caesarean delivery under combined-spinal
      epidural anaesthesia. Spinal anaesthesia consisted of either 8-10 mg of 0.5%
      bupivacaine alone (group B; n = 30) with 0.1 mg morphine (group BM0.1; n = 29),
      with 0.2 mg morphine (group BM0.2; n = 30), or with 10 mg pethidine (group
      BPeth10; n = 30). The incidences of shivering were 23.3% (7/30) in group B, 17%
      (5/29) in group BM0.1, 13.3% (4/30) in group BM0.2 and 3.3% (1/30) in group
      BPeth10 (p < 0.05). The shivering intensity for each patient was significantly
      higher in group B than the other groups. In conclusion, intrathecal pethidine
      added to hyperbaric bupivacaine reduces the incidence and intensity of shivering
      more than does morphine (0.1 or 0.2 mg).

PMID- 16288614
TI  - Use of the platelet function analyser (PFA-100) to quantify the effect of low
      dose aspirin in patients with ischaemic heart disease.
AB  - Continuing aspirin up until surgery in cardiac surgical patients may increase
      peri-operative blood loss. It is possible that there is a subset of patients
      particularly sensitive to aspirin. The platelet function analyser (PFA-100) can
      demonstrate the antiplatelet effect of aspirin. This study was designed to assess
      the effect of daily 75 mg aspirin on platelet function, as measured by the PFA
      100, in 92 patients with ischaemic heart disease. Patients were classified into
      three groups according to their PFA-100 results; aspirin hyper-responders (16%),
      aspirin normal responders (33%) and aspirin non-responders (51%). The PFA-100 has
      potential as a screening tool to identify patients who are either hyper
      responsive or resistant to aspirin. Pre-operative PFA-100 screening to isolate
      aspirin hyper-responders could enable the vast majority of patients to continue
      with aspirin therapy pre-operatively, avoiding the risks of stopping treatment.

PMID- 16288615
TI  - Histamine release during adult cardiopulmonary bypass.
AB  - Histamine, an inflammatory mediator in its own right, may also be a marker for a
      more widespread systemic inflammatory process. In this study we have examined
      variations in plasma histamine concentrations produced during the course of
      cardiac surgery involving cardiopulmonary bypass, the relationship between these
      variations and intra-operative events. By assays of serum tryptase and CD-63
      expression we have also attempted to identify the source of histamine. Histamine
      concentrations that were significantly raised from baseline level were
      demonstrated. These were elevated from the time of aortic cross-clamping and
      continued to be raised for 24 h postoperatively (p < 0.00625). This was
      associated with an increase in CD-63 expression (p < 0.025) (but not an increase
      in tryptase concentration) following aortic cross-clamping and protamine
      administration, suggesting that basophils are the source of histamine. 41% of
      patients had arrhythmias in the post bypass period. The rise in histamine levels
      was not related to the incidence of cardiac arrhythmias.

PMID- 16288616
TI  - Evaluation of capsaicin ointment at the Korean hand acupressure point K-D2 for
      prevention of postoperative nausea and vomiting.
AB  - The K-D2 point is the Korean hand acupressure point in Koryo Hand Therapy for
      prevention of postoperative nausea and vomiting. We evaluated the efficacy of
      capsaicin ointment at the K-D2 point in 186 patients undergoing laparoscopic
      cholecystectomy in a randomised, prospective, double-blind and placebo-controlled
      study. Patients were randomised to have either placebo ointment or capsaicin
      ointment applied to the K-D2 point of both hands 1 h before surgery under
      standardised anaesthesia. The ointment was removed 8 h later. Postoperative
      nausea and vomiting was evaluated 6 and 24 h following surgery. The incidence of
      postoperative nausea and vomiting was lower in the capsaicin group, with an
      absolute risk reduction (ARR) of 21%, a relative risk reduction (RRR) of 50% and
      a number-needed-to-treat (NNT) of 5 at 0-6 h (p = 0.001), and an ARR of 11%, a
      RRR of 85% and a NNT of 9 at 6-24 h (p = 0.003). The need for rescue anti-emetic
      treatment was also lower at 0-6 h (3 (3%) vs 11 (12%); p = 0.04) and at 6-24 h (5
      (5%) vs 0; p = 0.02).

PMID- 16288617
TI  - A procedure-specific systematic review and consensus recommendations for
      analgesia after total hip replacement.
AB  - Total hip replacement is a major surgical procedure usually associated with
      significant pain in the early postoperative period. Several anaesthetic and
      analgesic techniques are in common clinical use for this procedure but, to date,
      clinical studies of pain after total hip replacement have not been systematically
      assessed. Using the Cochrane protocol, we have conducted a systematic review of
      analgesic, anaesthetic and surgical interventions affecting postoperative pain
      after total hip replacement. In addition to the review, transferable evidence
      from other relevant procedures and clinical practice observations collated by the
      Delphi method were used to develop evidence-based recommendations for the
      treatment of postoperative pain. For primary total hip replacement, PROSPECT
      recommends either general anaesthesia combined with a peripheral nerve block that
      is continued after surgery or an intrathecal (spinal) injection of local
      anaesthetic and opioid. The primary analgesic technique should be combined with a
      step-down approach using paracetamol plus conventional non-steroidal anti
      inflammatory drugs, with strong or weak opioids as required.

PMID- 16288618
TI  - Recombinant activated factor VII and the anaesthetist.
AB  - Recombinant activated factor VII is a safe and effective for the treatment and
      prevention of haemorrhage in haemophiliacs with circulating inhibitors to
      replacement factors, and patients with Glanzmann's thrombasthenia refractory to
      platelet transfusion. By restoring thrombin generation on the surface of tissue
      factor bearing cells, such as activated platelets and monocytes, recombinant
      activated factor VII has the potential to effect haemostasis in the setting of
      many coagulopathic states encountered by the anaesthetist in the operating
      theatre or the intensive care unit. Case reports of successful rescue therapy
      make up the majority of the literature covering other, numerous, off-label uses
      of recombinant activated factor VII, although some randomised, controlled
      studies, mostly underpowered to address safety concerns, have been performed.
      However, off-label use is becoming increasingly popular judging by the number of
      published case reports. Additional randomised, controlled trials to determine the
      safe and appropriate use of this potentially valuable therapy in broader patient
      groups are eagerly awaited.

PMID- 16288619
TI  - Military influence upon the development of anaesthesia from the American Civil
      War (1861-1865) to the outbreak of the First World War.
AB  - The American Civil War (1861-1865) helped cement the place of anaesthesia in
      American medical practice and offered new insights into the specialty. The
      advantages that ensued were to offer long-term security to anaesthesia but the
      short-term gains were negligible. The Franco-Prussian War (1870-1871) exerted a
      negative influence upon nitrous oxide and oxygen research through the loss of
      leading civilian scientists to military duty. Later, the Boer Wars (1899-1902)
      helped stabilise the popularity of chloroform after the Hyderabad Commissions but
      were of little experimental value to anaesthesia. In the early 20th Century, the
      military continued to be operational without either specialist anaesthetists or
      an interest in developing military anaesthesia. However, the lack of anaesthetic
      development was largely due to problems with economics and academic
      infrastructure rather than to simple military neglect.

PMID- 16288620
TI  - A randomised comparison of the Portex Softseal laryngeal mask airway with the LMA
      Unique during anaesthesia.
AB  - We have compared the performance of the single use laryngeal airway devices
      Softseal and LMA-Unique in a randomised comparative trial in anaesthetised
      healthy patients who did not receive neuromuscular blockade. Primary outcome was
      success of airway placement. Secondary outcomes included manipulations and
      complications during use, ease of insertion, airway and fibreoptic assessment of
      airway positioning, and complications postoperatively. We planned to study 300
      patients but interim analysis demonstrated the study should be stopped after 100
      patients. During insertion the Softseal required more attempts for successful
      insertion (p = 0.041), more manipulations (p < 0.0001) and caused more
      complications (p = 0.048). Failure of placement occurred in five cases with the
      Softseal and none with the LMA-Unique (p = n/s). Two Softseal needed to be
      removed during maintenance because of airway obstruction, giving an overall
      failure rate of seven (p = 0.013). Serial tests of positioning favoured the LMA
      Unique (p = 0.012). Ventilation was more successful in the LMA-Unique group but
      the difference was not significant (p = 0.051). Seal pressure was higher with the
      Softseal (26.5 vs. 20.5 cmH(2)O, p = 0.005). Fibreoptic view via the devices was
      not statistically significantly different. During maintenance of anaesthesia more
      complications arose with the Softseal (p = 0.03). Anaesthetist ratings of ease of
      insertion and overall usefulness favoured the LMA-Unique (p < 0.0001 and p =
      0.024, respectively). After anaesthesia, sore throat occurred more frequently and
      was more severe in those patients anaesthetised with a Softseal both in recovery
      (p = 0.015) and at 24 h (p = 0.012). We conclude that the Softseal performs less
      well and causes more complications than the LMA-Unique.

PMID- 16288621
TI  - Xenon measurement in breathing systems: a comparison of ultrasonic and thermal
      conductivity methods.
AB  - Xenon is an anaesthetic and possibly neuroprotective gas that is impossible to
      measure using conventional anaesthetic gas analysers. We compared the performance
      of two commissioned xenon analysers using ultrasonic and thermal conductivity
      principles against a reference method of laser refractometry. An experimental gas
      circuit was constructed and xenon concentrations compared over a range of 0-100%
      in oxygen. Eighty-two paired measurements were made comparing the experimental
      methods with laser refractometry. The ultrasonic method displayed good agreement
      with laser refractometry, with a mean difference of - 0.74% and two standard
      deviation limits of agreement of + 1.08% to - 2.56%. The agreement between laser
      refractometry and thermal conductivity was poor, the mean difference being -
      5.37%, with two standard deviation limits of agreement of + 0.6% to - 11.3%. The
      ultrasonic method for measuring xenon concentrations can be used in breathing
      circuits. The thermal conductivity instrument may need further development.

PMID- 16288622
TI  - Survival after massive bleeding into the airway in a patient at risk from "can't
      intubate, can't ventilate".
AB  - A patient survived massive bleeding into the airway due to blowout of the right
      internal jugular vein associated with a failed free-flap graft for pharyngeal
      malignancy. A recently decannulated "covering tracheostomy" could not be easily
      re-established. Direct laryngoscopy and mask ventilation were inappropriate
      because the pharyngeal mucosal wound opened spontaneously and progressively and
      bleeding was dramatic. Positive pressure ventilation via a facemask risked
      widespread surgical emphysema and further wound disruption and because bleeding
      was from the internal jugular vein, there would also have been a risk of air
      embolism. The clinical situation evolved rapidly so time management and
      consideration of hierarchy of mortality risks was critical. It was eventually
      possible to re-establish the previous tracheostomy site as a result of close co
      operation between the surgical and anaesthetic teams. In difficult intubation
      where the problems are anticipated, the notion of responsive contingency planning
      is suggested to be of more general relevance than the current standard of
      considering alternative fallback options. The limitations of conventional
      capnography in this situation are also noteworthy.

PMID- 16288623
TI  - Transient paralysis after administration of a single dose of cyclizine.
AB  - Two patients with underlying neuromuscular disorders developed varying degrees of
      paralysis after a single dose of cyclizine, one necessitating full mechanical
      ventilation. These cases appear to be unique in the literature and represent an
      increasing spectrum of adverse reactions seen with the greater use of cyclizine.

PMID- 16288624
TI  - Ephedrine, phenylephrine and fetal acidosis.

PMID- 16288625
TI  - Spinal anaesthesia for Caesarean section and fetal acidosis.

PMID- 16288626
TI  - What babies want.

PMID- 16288627
TI  - Paternity of the Doughty technique.

PMID- 16288628
TI  - Intrathecal catheters after dural puncture--some unanswered questions.

PMID- 16288629
TI  - Recombinant Factor VIIa in blunt pelvic trauma.

PMID- 16288630
TI  - Patient-controlled opioid analgesia for labour.

PMID- 16288631
TI  - Prophylactic percutaneous transtracheal catheterisation.

PMID- 16288632
TI  - Hydrocortisone preparations and latex.

PMID- 16288633
TI  - Failure of an intravenous cannula.

PMID- 16288634
TI  - Generic machine checks.

PMID- 16288635
TI  - GMC guidance upheld.

PMID- 16288636
TI  - Reflectance pulse oximeter-associated burn in a critically ill patient.

PMID- 16288637
TI  - Potential air embolus from a Level 1 Rapid Infuser.

PMID- 16288638
TI  - Use of a blunt drawing-up needle for ilio-inguinal blocks.

PMID- 16288639
TI  - Are all the single-use laryngeal masks the same?

PMID- 16288640
TI  - Failure of a single use laryngeal mask airway.

PMID- 16288641
TI  - Damage to armoured tracheal tubes by CUSA.

PMID- 16288646
TI  - The costs of reducing loss to follow-up in South African cervical cancer
      screening.
AB  - BACKGROUND: This study was designed to quantify the resources used in
      reestablishing contact with women who missed their scheduled cervical cancer
      screening visits and to assess the success of this effort in reducing loss to
      follow-up in a developing country setting. METHODS: Women were enrolled in this
      Cape Town, South Africa-based screening study between 2000 and 2003, and all had
      scheduled follow-up visits in 2003. Community health worker (CHW) time, vehicle
      use, maintenance, and depreciation were estimated from weekly logs and cost
      accounting systems. The percentage of women who attended their scheduled visit,
      those who attended after CHW contact(s), and those who never returned despite
      attempted contact(s) were determined. The number of CHW visits per woman was also
      estimated. RESULTS: 3,711 visits were scheduled in 2003. Of these, 2,321 (62.5%)
      occurred without CHW contact, 918 (24.8%) occurred after contact(s), and 472
      (12.7%) did not occur despite contact(s). Loss to follow-up was reduced from 21%
      to 6%, 39% to 10%, and 50% to 24% for 6, 12, and 24-month visits. CHWs attempted
      3,200 contacts in 530 trips. On average, 3 CHWs attempted to contact 6
      participants over each 111 minute trip. The per-person cost (2003 Rand) for these
      activities was 12.75, 24.92, and 40.50 for 6, 12, and 24-month visits.
      CONCLUSION: CHW contact with women who missed scheduled visits increased their
      return rate. Cost-effectiveness analyses aimed at policy decisions about cervical
      cancer screening in developing countries should incorporate these findings.

PMID- 16288647
TI  - Brazilian obstetrician-gynecologists and abortion: a survey of knowledge,
      opinions and practices.
AB  - BACKGROUND: Abortion laws are extremely restrictive in Brazil. The knowledge,
      opinions of abortion laws, and abortion practices of obstetrician-gynecologists
      can have a significant impact on women's access to safe abortion. METHODS: We
      conducted a mail-in survey with a 10% random sample of obstetrician-gynecologists
      affiliated with the Brazilian Federation of Obstetricians and Gynecologists. We
      documented participants' experiences performing abortion under a range of legal
      and illegal circumstances, and asked about which abortion techniques they had
      experience with. We used chi-square tests and crude logistic regression models to
      determine which sociodemographic, knowledge-related, or practice-related
      variables were associated with physician opinion. RESULTS: Of the 1,500
      questionnaires that we mailed out, we received responses from 572 (38%). Less
      than half (48%) of the respondents reported accurate knowledge about abortion law
      and 77% thought that the law should be more liberal. One-third of respondents
      reported having previous experience performing an abortion, and very few of these
      physicians reported having experience with manual vacuum aspiration (MVA) or with
      misoprostol with either mifepristone or methotrexate. Physicians that favored
      liberalization of the law were more likely to have correct knowledge about
      abortion law, and to be in favor of public funding for abortion services.
      CONCLUSION: Brazilian obstetrician-gynecologists need more information on
      abortion laws and on safe, effective abortion procedures.

PMID- 16288648
TI  - Describing the longitudinal course of major depression using Markov models: data
      integration across three national surveys.
AB  - BACKGROUND: Most epidemiological studies of major depression report period
      prevalence estimates. These are of limited utility in characterizing the
      longitudinal epidemiology of this condition. Markov models provide a
      methodological framework for increasing the utility of epidemiological data.
      Markov models relating incidence and recovery to major depression prevalence have
      been described in a series of prior papers. In this paper, the models are
      extended to describe the longitudinal course of the disorder. METHODS: Data from
      three national surveys conducted by the Canadian national statistical agency
      (Statistics Canada) were used in this analysis. These data were integrated using
      a Markov model. Incidence, recurrence and recovery were represented as weekly
      transition probabilities. Model parameters were calibrated to the survey
      estimates. RESULTS: The population was divided into three categories: low,
      moderate and high recurrence groups. The size of each category was approximated
      using lifetime data from a study using the WHO Mental Health Composite
      International Diagnostic Interview (WMH-CIDI). Consistent with previous work,
      transition probabilities reflecting recovery were high in the initial weeks of
      the episodes, and declined by a fixed proportion with each passing week.
      CONCLUSION: Markov models provide a framework for integrating psychiatric
      epidemiological data. Previous studies have illustrated the utility of Markov
      models for decomposing prevalence into its various determinants: incidence,
      recovery and mortality. This study extends the Markov approach by distinguishing
      several recurrence categories.

PMID- 16288649
TI  - Bacterial meningitis in children and adolescents: an observational study based on
      the national surveillance system.
AB  - BACKGROUND: Bacterial meningitis is a group of life threatening infections that
      mostly affect children and adolescents, and may be the cause of severe
      neurological sequelae. Cuba has implemented massive vaccination programmes
      against both Neisseria meningitidis (serogroup C in 1979 and B in 1987), and
      Haemophilus influenzae type b (1999), two of the main causal pathogens. We
      described and discussed some epidemiological aspects of the current status of
      bacterial meningitis to learn from the Cuban experience. METHODS: A nationwide
      observational study on children and adolescents from 1 to 18 years old was
      carried out from 1998 to 2003, estimating the incidence and case-fatality rate by
      age group and causal pathogens, as well as the seasonality and frequency of
      overcrowded dormitories. The association between disease and attendance to day
      care centres or boarding schools was estimated by using relative risk (Chi
      squared test and Fisher Exact Test). RESULTS: The overall number of cases was
      1023; the incidence ranged from 3.4 to 8.5 per 100,000 population, with the
      higher figures in children 1-5 years old (16.8 per 100,000 population).
      Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria
      meningitidis serogroup B were the main identified agents. The average case
      fatality rate was 10.5% and the most lethal agents were Streptococcus pneumoniae
      (27%) and Haemophilus influenzae type b (10.7%). Overall percentage of cases who
      slept in overcrowded dormitories was 15%, reaching 30.6% in adolescents.
      Seasonality was only evident among meningococcal meningitis cases between
      September-October. The attendance to boarding high school showed an association
      with disease only in 1998 and 1999 (RR = 2.1; p > 0.05). CONCLUSION: The highest
      incidence of bacterial meningitis was observed among children from 1-5 years old.
      Pneumococcus was both the leading causal and the most lethal agent. Sleeping in
      overcrowded dormitories was more frequent among adolescents. No strong
      association was observed between the bacterial meningitis and attendance to day
      care centres or boarding schools. The incidence of bacterial meningitis in Cuba
      is declining after massive vaccination programmes against Neisseria meningitidis
      serogroup B and C and Haemophilus influenzae type b through a national
      immunisation program.

PMID- 16288650
TI  - Quality of life in bipolar disorder: a review of the literature.
AB  - A sizable body of research has now examined the complex relationship between
      quality of life (QoL) and depressive disorder. Uptake of QoL research in relation
      to bipolar disorder (BD) has been comparatively slow, although increasing numbers
      of QoL studies are now being conducted in bipolar populations. We aimed to
      perform a review of studies addressing the assessment of generic and health
      related QoL in patients with bipolar disorder. A literature search was conducted
      in a comprehensive selection of databases including MEDLINE up to November 2004.
      Key words included: bipolar disorder or manic-depression, mania, bipolar
      depression, bipolar spectrum and variants AND quality of life, health-related
      QoL, functional status, well-being and variants. Articles were included if they
      were published in English and reported on an assessment of generic or health
      related QoL in patients with BD. Articles were not included if they had assessed
      fewer than 10 patients with BD, were only published in abstract form or only
      assessed single dimensions of functioning. The literature search initially
      yielded 790 articles or abstracts. Of these, 762 did not meet our inclusion
      criteria, leaving a final total of 28 articles. These were sub-divided into four
      categories (assessment of QoL in patients with BD at different stages of the
      disorder, comparisons of QoL in patients with BD with that of other patient
      populations, QoL instrument evaluation in patients with BD and treatment studies
      using QoL instruments to assess outcome in Patients with BD) and described in
      detail. The review indicated that there is growing interest in QoL research in
      bipolar populations. Although the scientific quality of the research identified
      was variable, increasing numbers of studies of good design are being conducted.
      The majority of the studies we identified indicated that QoL is markedly impaired
      in patients with BD, even when they are considered to be clinically euthymic. We
      identified several important avenues for future research, including a need for
      more assessment of QoL in hypo/manic patients, more longitudinal research and the
      development of a disease-specific measure of QoL for patients with BD.

PMID- 16288651
TI  - Leveraging human genomic information to identify nonhuman primate sequences for
      expression array development.
AB  - BACKGROUND: Nonhuman primates (NHPs) are essential for biomedical research due to
      their similarities to humans. The utility of NHPs will be greatly increased by
      the application of genomics-based approaches such as gene expression profiling.
      Sequence information from the 3' end of genes is the key resource needed to
      create oligonucleotide expression arrays. RESULTS: We have developed the
      algorithms and procedures necessary to quickly acquire sequence information from
      the 3' end of nonhuman primate orthologs of human genes. To accomplish this, we
      identified terminal exons of over 15,000 human genes by aligning mRNA sequences
      with genomic sequence. We found the mean length of complete last exons to be
      approximately 1,400 bp, significantly longer than previous estimates. We designed
      primers to amplify genomic DNA, which included at least 300 bp of the terminal
      exon. We cloned and sequenced the PCR products representing over 5,500 Macaca
      mulatta (rhesus monkey) orthologs of human genes. This sequence information has
      been used to select probes for rhesus gene expression profiling. We have also
      tested 10 sets of primers with genomic DNA from Macaca fascicularis (Cynomolgus
      monkey), Papio hamadryas (Baboon), and Chlorocebus aethiops (African green
      monkey, vervet). The results indicate that the primers developed for this study
      will be useful for acquiring sequence from the 3' end of genes for other nonhuman
      primate species. CONCLUSION: This study demonstrates that human genomic DNA
      sequence can be leveraged to obtain sequence from the 3' end of NHP orthologs and
      that this sequence can then be used to generate NHP oligonucleotide microarrays.
      Affymetrix and Agilent used sequences obtained with this approach in the design
      of their rhesus macaque oligonucleotide microarrays.

PMID- 16288652
TI  - Automated methods of predicting the function of biological sequences using GO and
      BLAST.
AB  - BACKGROUND: With the exponential increase in genomic sequence data there is a
      need to develop automated approaches to deducing the biological functions of
      novel sequences with high accuracy. Our aim is to demonstrate how accuracy
      benchmarking can be used in a decision-making process evaluating competing
      designs of biological function predictors. We utilise the Gene Ontology, GO, a
      directed acyclic graph of functional terms, to annotate sequences with functional
      information describing their biological context. Initially we examine the effect
      on accuracy scores of increasing the allowed distance between predicted and a
      test set of curator assigned terms. Next we evaluate several annotator methods
      using accuracy benchmarking. Given an unannotated sequence we use the Basic Local
      Alignment Search Tool, BLAST, to find similar sequences that have already been
      assigned GO terms by curators. A number of methods were developed that utilise
      terms associated with the best five matching sequences. These methods were
      compared against a benchmark method of simply using terms associated with the
      best BLAST-matched sequence (best BLAST approach). RESULTS: The precision and
      recall of estimates increases rapidly as the amount of distance permitted between
      a predicted term and a correct term assignment increases. Accuracy benchmarking
      allows a comparison of annotation methods. A covering graph approach performs
      poorly, except where the term assignment rate is high. A term distance
      concordance approach has a similar accuracy to the best BLAST approach,
      demonstrating lower precision but higher recall. However, a discriminant function
      method has higher precision and recall than the best BLAST approach and other
      methods shown here. CONCLUSION: Allowing term predictions to be counted correct
      if closely related to a correct term decreases the reliability of the accuracy
      score. As such we recommend using accuracy measures that require exact matching
      of predicted terms with curator assigned terms. Furthermore, we conclude that
      competing designs of BLAST-based GO term annotators can be effectively compared
      using an accuracy benchmarking approach. The most accurate annotation method was
      developed using data mining techniques. As such we recommend that designers of
      term annotators utilise accuracy benchmarking and data mining to ensure newly
      developed annotators are of high quality.

PMID- 16288653
TI  - Mechanisms of escape phenomenon of spinal cord and brainstem in human rabies.
AB  - BACKGROUND: Rabies virus preferentially involves brainstem, thalamus and spinal
      cord in human furious and paralytic rabies beginning in the early stage of
      illness. Nevertheless, rabies patient remains alert until the pre-terminal phase.
      Weakness of extremities develops only when furious rabies patient becomes
      comatose; whereas peripheral nerve dysfunction is responsible for weakness in
      paralytic rabies. METHODS: Evidence of apoptosis and mitochondrial outer membrane
      permeabilization in brain and spinal cord of 10 rabies patients was examined and
      these findings were correlated with the presence of rabies virus antigen.
      RESULTS: Although apoptosis was evident in most of the regions, cytochrome c
      leakage was relatively absent in spinal cord of nearly all patients despite the
      abundant presence of rabies virus antigen. Such finding was also noted in
      brainstem of 5 patients. CONCLUSION: Cell death in human rabies may be delayed in
      spinal cord and the reticular activating system, such as brainstem, thus
      explaining absence of weakness due to spinal cord dysfunction and preservation of
      consciousness.

PMID- 16288654
TI  - The SDH mutation database: an online resource for succinate dehydrogenase
      sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial
      complex II deficiency.
AB  - BACKGROUND: The SDHA, SDHB, SDHC and SDHD genes encode the subunits of succinate
      dehydrogenase (succinate: ubiquinone oxidoreductase), a component of both the
      Krebs cycle and the mitochondrial respiratory chain. SDHA, a flavoprotein and
      SDHB, an iron-sulfur protein together constitute the catalytic domain, while SDHC
      and SDHD encode membrane anchors that allow the complex to participate in the
      respiratory chain as complex II. Germline mutations of SDHD and SDHB are a major
      cause of the hereditary forms of the tumors paraganglioma and pheochromocytoma.
      The largest subunit, SDHA, is mutated in patients with Leigh syndrome and late
      onset optic atrophy, but has not as yet been identified as a factor in hereditary
      cancer. DESCRIPTION: The SDH mutation database is based on the recently described
      Leiden Open (source) Variation Database (LOVD) system. The variants currently
      described in the database were extracted from the published literature and in
      some cases annotated to conform to current mutation nomenclature. Researchers can
      also directly submit new sequence variants online. Since the identification of
      SDHD, SDHC, and SDHB as classic tumor suppressor genes in 2000 and 2001, studies
      from research groups around the world have identified a total of 120 variants.
      Here we introduce all reported paraganglioma and pheochromocytoma related
      sequence variations in these genes, in addition to all reported mutations of
      SDHA. The database is now accessible online. CONCLUSION: The SDH mutation
      database offers a valuable tool and resource for clinicians involved in the
      treatment of patients with paraganglioma-pheochromocytoma, clinical geneticists
      needing an overview of current knowledge, and geneticists and other researchers
      needing a solid foundation for further exploration of both these tumor syndromes
      and SDHA-related phenotypes.

PMID- 16288656
TI  - Are associations between socio-economic characteristics and exposure to air
      pollution a question of study area size? An example from Scania, Sweden.
AB  - BACKGROUND: Numerous studies have shown that exposure to air pollutants in the
      area of residence and the socio-economic status of an individual may be related.
      Therefore, when conducting an epidemiological study on the health effect of air
      pollution, socio-economy may act as a confounding factor. In this paper we
      examine to what extent socio-economic status and concentrations of NO2 in the
      county/region of Scania, southern Sweden, are associated and if such associations
      between these factors differ when studying them at county or city level. To
      perform this study we used high-resolution census data and modelled the annual
      exposure to NO2 using an emission database, a dispersion modelling program and a
      geographical information system (GIS). RESULTS: The results from this study
      confirm that socio-economic status and the levels of NO2 in the area of residence
      are associated in some cities. The associations vary considerably between cities
      within the same county (Scania). Even for cities of similar sizes and population
      bases the associations observed are different. Studying the cities together or
      separately yields contradictory results, especially when education is used as a
      socio-economic indicator. CONCLUSION: Four conclusions have been drawn from the
      results of this study. 1) Adjusting for socio-economy is important when
      investigating the health effects of air pollution. 2) The county of Scania seems
      to be heterogeneous regarding the association between air pollution and socio
      economy. 3) The relationship between air pollution and socio-economy differs in
      the five cities included in our study, depending on whether they are analysed
      separately or together. It is therefore inadvisable to determine and analyse
      associations between socio-economy and exposure to air pollutants on county
      level. This study indicates that the size and choice of study area is of great
      importance. 4) The selection of socio-economic indices (in this study: country of
      birth and education level) is important.

PMID- 16288655
TI  - Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic
      Syndrome may be defined by the response to carbohydrate restriction.
AB  - Metabolic Syndrome (MetS) represents a constellation of markers that indicates a
      predisposition to diabetes, cardiovascular disease and other pathologic states.
      The definition and treatment are a matter of current debate and there is not
      general agreement on a precise definition or, to some extent, whether the
      designation provides more information than the individual components. We consider
      here five indicators that are central to most definitions and we provide evidence
      from the literature that these are precisely the symptoms that respond to
      reduction in dietary carbohydrate (CHO). Carbohydrate restriction is one of
      several strategies for reducing body mass but even in the absence of weight loss
      or in comparison with low fat alternatives, CHO restriction is effective at
      ameliorating high fasting glucose and insulin, high plasma triglycerides (TAG),
      low HDL and high blood pressure. In addition, low fat, high CHO diets have long
      been known to raise TAG, lower HDL and, in the absence of weight loss, may worsen
      glycemic control. Thus, whereas there are numerous strategies for weight loss, a
      patient with high BMI and high TAG is likely to benefit most from a regimen that
      reduces CHO intake. Reviewing the literature, benefits of CHO restriction are
      seen in normal or overweight individuals, in normal patients who meet the
      criteria for MetS or in patients with frank diabetes. Moreover, in low fat
      studies that ameliorate LDL and total cholesterol, controls may do better on the
      symptoms of MetS. On this basis, we feel that MetS is a meaningful, useful
      phenomenon and may, in fact, be operationally defined as the set of markers that
      responds to CHO restriction. Insofar as this is an accurate characterization it
      is likely the result of the effect of dietary CHO on insulin metabolism. Glucose
      is the major insulin secretagogue and insulin resistance has been tied to the
      hyperinsulinemic state or the effect of such a state on lipid metabolism. The
      conclusion is probably not surprising but has not been explicitly stated before.
      The known effects of CHO-induced hypertriglyceridemia, the HDL-lowering effect of
      low fat, high CHO interventions and the obvious improvement in glucose and
      insulin from CHO restriction should have made this evident. In addition, recent
      studies suggest that a subset of MetS, the ratio of TAG/HDL, is a good marker for
      insulin resistance and risk of CVD, and this indicator is reliably reduced by CHO
      restriction and exacerbated by high CHO intake. Inability to make this connection
      in the past has probably been due to the fact that individual responses have been
      studied in isolation as well as to the emphasis of traditional therapeutic
      approaches on low fat rather than low CHO. We emphasize that MetS is not a
      disease but a collection of markers. Individual physicians must decide whether
      high LDL, or other risk factors are more important than the features of MetS in
      any individual case but if MetS is to be considered it should be recognized that
      reducing CHO will bring improvement. Response of symptoms to CHO restriction
      might thus provide a new experimental criterion for MetS in the face of on-going
      controversy about a useful definition. As a guide to future research, the idea
      that control of insulin metabolism by CHO intake is, to a first approximation,
      the underlying mechanism in MetS is a testable hypothesis.

PMID- 16288657
TI  - Ethnomedicinal botany of the Apatani in the Eastern Himalayan region of India.
AB  - This paper investigates the wealth of medicinal plants used by the Apatani tribe
      of Arunachal Pradesh. Apatani have traditionally settled in seven villages in the
      Ziro valley of Lower Subansiri district of Arunachal Pradesh in the Eastern
      Himalayan region of India. The present study has resulted in the documentation of
      158 medicinal plant species used by the Apatani group of villages. These
      medicinal plant species were distributed across 73 families and 124 genera.
      Asteraceae was the most dominant family (19 species, 11 genera) of medicinal
      plants, followed by Zingiberaceae, Solanaceae, Lamiaceae and Araceae. For curing
      ailments, the use of aboveground plant parts was higher (80%) than the
      belowground plant parts in the Apatani group of villages. Of the aboveground
      plant parts, leaf was used in the majority of cases (56 species), followed by
      fruit. Different belowground plant forms such as root, tuber, rhizome, bulb and
      pseudo-bulb were used by Apatani as a medicine. About 52 types of ailments were
      cured by using these 158 medicinal plant species. The results of this study are
      further discussed in the changing socio-economic contexts.

PMID- 16288658
TI  - Construction and characterization of a genomic BAC library for the Mus m.
      musculus mouse subspecies (PWD/Ph inbred strain).
AB  - BACKGROUND: The genome of classical laboratory strains of mice is an artificial
      mosaic of genomes originated from several mouse subspecies with predominant
      representation (>90%) of the Mus m. domesticus component. Mice of another
      subspecies, East European/Asian Mus m. musculus, can interbreed with the
      classical laboratory strains to generate hybrids with unprecedented phenotypic
      and genotypic variations. To study these variations in depth we prepared the
      first genomic large insert BAC library from an inbred strain derived purely from
      the Mus m. musculus-subspecies. The library will be used to seek and characterize
      genomic sequences controlling specific monogenic and polygenic complex traits,
      including modifiers of dominant and recessive mutations. RESULTS: A
      representative mouse genomic BAC library was derived from a female mouse of the
      PWD/Ph inbred strain of Mus m. musculus subspecies. The library consists of
      144,768 primary clones from which 97% contain an insert of 120 kb average size.
      The library represents an equivalent of 6.7 x mouse haploid genome, as estimated
      from the total number of clones carrying genomic DNA inserts and from the average
      insert size. The clones were arrayed in duplicates onto eight high-density
      membranes that were screened with seven single-copy gene probes. The individual
      probes identified four to eleven positive clones, corresponding to 6.9-fold
      coverage of the mouse genome. Eighty-seven BAC-ends of PWD/Ph clones were
      sequenced, edited, and aligned with mouse C57BL/6J (B6) genome. Seventy-three BAC
      ends displayed unique hits on B6 genome and their alignment revealed 0.92 single
      nucleotide polymorphisms (SNPs) per 100 bp. Insertions and deletions represented
      0.3% of the BAC end sequences. CONCLUSION: Analysis of the novel genomic library
      for the PWD/Ph inbred strain demonstrated coverage of almost seven mouse genome
      equivalents and a capability to recover clones for specific regions of PWD/Ph
      genome. The single nucleotide polymorphism between the strains PWD/Ph and
      C57BL/6J was 0.92/100 bp, a value significantly higher than between classical
      laboratory strains. The library will serve as a resource for dissecting the
      phenotypic and genotypic variations between mice of the Mus m. musculus
      subspecies and classical laboratory mouse strains.

PMID- 16288659
TI  - Response of religious groups to HIV/AIDS as a sexually transmitted infection in
      Trinidad.
AB  - BACKGROUND: HIV/AIDS-related stigma and discrimination are significant
      determinants of HIV transmission in the Caribbean island nation of Trinidad and
      Tobago (T&T), where the adult HIV/AIDS prevalence is 2.5%. T&T is a spiritually
      aware society and over 104 religious groups are represented. This religious
      diversity creates a complex social environment for the transmission of a sexually
      transmitted infection like HIV/AIDS. Religious leaders are esteemed in T&T's
      society and may use their position and frequent interactions with the public to
      promote HIV/AIDS awareness, fight stigma and discrimination, and exercise
      compassion for people living with HIV/AIDS (PWHA). Some religious groups have
      initiated HIV/AIDS education programs within their membership, but previous
      studies suggest that HIV/AIDS remains a stigmatized infection in many religious
      organizations. The present study investigates how the perception of HIV/AIDS as a
      sexually transmitted infection impacts religious representatives' incentives to
      respond to HIV/AIDS in their congregations and communities. In correlation, the
      study explores how the experiences of PWHA in religious gatherings impact healing
      and coping with HIV/AIDS. METHODS: Between November 2002 and April 2003, in-depth
      interviews were conducted with 11 religious representatives from 10 Christian,
      Hindu and Muslim denominations. The majority of respondents were leaders of
      religious services, while two were active congregation members. Religious groups
      were selected based upon the methods of Brathwaite. Briefly, 26 religious groups
      with the largest followings according to 2000 census data were identified in
      Trinidad and Tobago. From this original list, 10 religious groups in Northwest
      Trinidad were selected to comprise a representative sample of the island's main
      denominations. In-depth interviews with PWHA were conducted during the same study
      period, 2002-2003. Four individuals were selected from a care and support group
      located in Port of Spain based upon their perceived willingness to discuss
      religious affiliation and describe how living with a terminal infection has
      affected their spiritual lives. The interviewer, a United States Fulbright
      Scholar, explained the nature and purpose of the study to all participants.
      Relevant ethical procedures associated with the collection of interview data were
      adopted: interviews were conducted in a non-coercive manner and confidentiality
      was assured. All participants provided verbal consent, and agreed to be
      interviewed without financial or other incentive. Ethics approval was granted on
      behalf of the Caribbean Conference of Churches Ethics Committee. Interview
      questions followed a guideline, and employed an open-ended format to facilitate
      discussion. All interviews were recorded and transcribed by the interviewer.
      RESULTS: Religious representatives' opinions were grouped into the following
      categories: rationale for the spread of HIV/AIDS, abstinence, condom use,
      sexuality and homosexuality, compassion, experiences with PWHA, recommendations
      and current approach to addressing HIV/AIDS in congregations. Religious
      representatives expressed a measure of acceptance of HIV/AIDS and overwhelmingly
      upheld compassion for PWHA. Some statements, however, suggested that HIV/AIDS
      stigma pervades Trinidad's religious organizations. For many representatives,
      HIV/AIDS was associated with a promiscuous lifestyle and/or homosexuality.
      Representatives had varying levels of interaction with PWHA, but personal
      experiences were positively associated with current involvement in HIV/AIDS
      initiatives. All 4 PWHA interviewed identified themselves as belonging to
      Christian denominations. Three out of the 4 PWHA described discriminatory
      experiences with pastors or congregation members during gatherings for religious
      services. Nonetheless, PWHA expressed an important role for faith and religion in
      coping with HIV. CONCLUSION: Religious groups in Trinidad are being challenged to
      promote a clear and consistent response to the HIV/AIDS epidemic; a response that
      may reflect personal experiences and respect religious doctrine in the context of
      sex and sexuality. The study suggests that (1) religious leaders could improve
      their role in the fight against HIV/AIDS with education and sensitization
      specifically aimed at dismantling the myths about HIV transmission, and the
      stereotyping of susceptible sub-populations, and (2) a consultative dialogue
      between PWHAs and religious leaders is pivotal to a successful faith-based HIV
      intervention in Trinidad.

PMID- 16288660
TI  - Biology and physiology of Calbindin-D9k in female reproductive tissues:
      involvement of steroids and endocrine disruptors.
AB  - Although Calbindin-D9k (CaBP-9k), a cytosolic calcium binding protein which has
      calcium binding sites, is expressed in various tissues, i.e., intestine, uterus,
      and placenta, potential roles of this gene and its protein are not clearly
      understood. Uterine CaBP-9k may be involved in controlling myometrial activity
      related with intracellular calcium level and is not under the control of vitamin
      D despite the presence of vitamin D receptors. But, it is under the control of
      the sex steroid hormones, estrogen (E2) and progesterone (P4), in female
      reproductive systems including the uterus and placenta. Thus, in this review, we
      summarize recent research literature in regards to the expression and regulation
      of CaBP-9k in mammals and introduce the research data of recent studies by us and
      others.

PMID- 16288661
TI  - Touchdown General Primer (GP5+/GP6+) PCR and optimized sample DNA concentration
      support the sensitive detection of human papillomavirus.
AB  - BACKGROUND: The GP5+/GP6+ PCR assay is a well-established HPV detection
      technique. This study has examined the effects of incorporating 'hot start' and
      'touchdown' steps into the protocol. In addition, dTTP was substituted with dUTP
      to permit contamination control measures against carry-over PCR product. METHODS:
      Firstly, HPV-16 was amplified from SiHa cell DNA (0.1 ng-100 ng) diluted in a
      background of C-33A DNA (100 ng-2 microg). Secondly, the detection of small
      quantities (15ag-1.5pg) of HPV recombinant plasmids (types 16, 31, 33, 45, 51,
      52, and 56) diluted in C-33A DNA was investigated. Thirdly, clinical sample DNA
      extracts (cervical smears, formalin-fixed vaginal lesions and breast tumors) were
      tested for HPV. Six different PCR protocols were assessed. HPV was detected by
      gel electrophoresis, and by Southern and dot blot hybridization. RESULTS: HPV
      detection sensitivity was dependent on the total amount of DNA in a PCR.
      Touchdown protocols supported HPV-16 detection from 1 ng or 0.5 ng SiHa cell DNA
      in a background of 2 microg or 1 microg C-33A DNA respectively, and from 0.1 ng
      of SiHa cell DNA (approximately 28 copies HPV-16) in 500 ng or 100 ng background
      DNA. Under standard GP5+/GP6+ annealing conditions, HPV-16 went undetected when
      the DNA content of a PCR was 2 microg or 1 microg, and with 500 ng C-33A DNA the
      sensitivity limit was 1 ng SiHa cell DNA. HPV recombinant plasmids were each
      detected with high (albeit varying) sensitivity by a touchdown protocol. HPV-31
      was better amplified under standard annealing conditions (1.5fg in 100 ng
      background DNA) than by a touchdown approach (15fg detection limit). HPV-52 was
      not amplified by the standard protocol at the dilutions tested. Seventeen
      different HPV types were demonstrated in 47/65 (72%) abnormal cytology samples
      recorded as HPV negative by standard GP5+/GP6+ conditions. Twenty-one different
      HPV types were recorded in 111/114 (97%) vaginal lesions. Multiple infections
      were also detectable using a touchdown approach. Of 26 breast tumors, 5 (19%)
      tested HPV positive by the standard assay and 15/26 (58%) using a touchdown
      protocol. CONCLUSION: Touchdown modification of the GP5+/GP6+ PCR assay enables
      the detection of HPV undetected under regular assay conditions. The use of
      standardized DNA quantities in a PCR rather than standard sample volumes
      containing arbitrary amounts of DNA is supported. A touchdown approach may be
      beneficial as an analytical test for the re-evaluation of (apparently) HPV
      negative abnormal cervical cytological or histological samples, and for
      investigating the association of HPV with disease conditions at diverse organ
      sites. The clinical utility of a touchdown approach for HPV detection requires
      further investigation as increased assay analytical sensitivity may not
      necessarily equate with improved clinical sensitivity or specificity.

PMID- 16288663
TI  - Pscroph, a parasitic plant EST database enriched for parasite associated
      transcripts.
AB  - BACKGROUND: Parasitic plants in the Orobanchaceae develop invasive root haustoria
      upon contact with host roots or root factors. The development of haustoria can be
      visually monitored and is rapid, highly synchronous, and strongly dependent on
      host factor exposure; therefore it provides a tractable system for studying
      chemical communications between roots of different plants. DESCRIPTION:
      Triphysaria is a facultative parasitic plant that initiates haustorium
      development within minutes after contact with host plant roots, root exudates, or
      purified haustorium-inducing phenolics. In order to identify genes associated
      with host root identification and early haustorium development, we sequenced
      suppression subtractive libraries (SSH) enriched for transcripts regulated in
      Triphysaria roots within five hours of exposure to Arabidopsis roots or the
      purified haustorium-inducing factor 2,6 dimethoxybenzoquinone. The sequences of
      over nine thousand ESTs from three SSH libraries and their subsequent assemblies
      are available at the Pscroph database http://pscroph.ucdavis.edu. The web site
      also provides BLAST functions and allows keyword searches of functional
      annotations. CONCLUSION: Libraries prepared from Triphysaria roots treated with
      host roots or haustorium inducing factors were enriched for transcripts predicted
      to function in stress responses, electron transport or protein metabolism. In
      addition to parasitic plant investigations, the Pscroph database provides a
      useful resource for investigations in rhizosphere interactions, chemical
      signaling between organisms, and plant development and evolution.

PMID- 16288662
TI  - Coiled-coil protein composition of 22 proteomes--differences and common themes in
      subcellular infrastructure and traffic control.
AB  - BACKGROUND: Long alpha-helical coiled-coil proteins are involved in diverse
      organizational and regulatory processes in eukaryotic cells. They provide cables
      and networks in the cyto- and nucleoskeleton, molecular scaffolds that organize
      membrane systems and tissues, motors, levers, rotating arms, and possibly
      springs. Mutations in long coiled-coil proteins have been implemented in a
      growing number of human diseases. Using the coiled-coil prediction program
      MultiCoil, we have previously identified all long coiled-coil proteins from the
      model plant Arabidopsis thaliana and have established a searchable Arabidopsis
      coiled-coil protein database. RESULTS: Here, we have identified all proteins with
      long coiled-coil domains from 21 additional fully sequenced genomes. Because
      regions predicted to form coiled-coils interfere with sequence homology
      determination, we have developed a sequence comparison and clustering strategy
      based on masking predicted coiled-coil domains. Comparing and grouping all long
      coiled-coil proteins from 22 genomes, the kingdom-specificity of coiled-coil
      protein families was determined. At the same time, a number of proteins with
      unknown function could be grouped with already characterized proteins from other
      organisms. CONCLUSION: MultiCoil predicts proteins with extended coiled-coil
      domains (more than 250 amino acids) to be largely absent from bacterial genomes,
      but present in archaea and eukaryotes. The structural maintenance of chromosomes
      proteins and their relatives are the only long coiled-coil protein family clearly
      conserved throughout all kingdoms, indicating their ancient nature. Motor
      proteins, membrane tethering and vesicle transport proteins are the dominant
      eukaryote-specific long coiled-coil proteins, suggesting that coiled-coil
      proteins have gained functions in the increasingly complex processes of
      subcellular infrastructure maintenance and trafficking control of the eukaryotic
      cell.

PMID- 16288664
TI  - The International Classification of Functioning as an explanatory model of health
      after distal radius fracture: a cohort study.
AB  - BACKGROUND: Distal radius fractures are common injuries that have an increasing
      impact on health across the lifespan. The purpose of this study was to identify
      health impacts in body structure/function, activity, and participation at
      baseline and follow-up, to determine whether they support the ICF model of
      health. METHODS: This is a prospective cohort study of 790 individuals who were
      assessed at 1 week, 3 months, and 1 year post injury. The Patient Rated Wrist
      Evaluation (PRWE), The Wrist Outcome Measure (WOM), and the Medical Outcome
      Survey Short-Form (SF-36) were used to measure impairment, activity,
      participation, and health. Multiple regression was used to develop explanatory
      models of health outcome. RESULTS: Regression analysis showed that the PRWE
      explained between 13% (one week) and 33% (three months) of the SF-36 Physical
      Component Summary Scores with pain, activities and participation subscales
      showing dominant effects at different stages of recovery. PRWE scores were less
      related to Mental Component Summary Scores, 10% (three months) and 8% (one year).
      Wrist impairment scores were less powerful predictors of health status than the
      PRWE. CONCLUSION: The ICF is an informative model for examining distal radius
      fracture. Difficulty in the domains of activity and participation were able to
      explain a significant portion of physical health. Post-fracture rehabilitation
      and outcome assessments should extend beyond physical impairment to insure
      comprehensive treatment to individuals with distal radius fracture.

PMID- 16288666
TI  - Evidence-based physical therapy for the management of children with cerebral
      palsy.

PMID- 16288665
TI  - Assessing the precision of high-throughput computational and laboratory
      approaches for the genome-wide identification of protein subcellular localization
      in bacteria.
AB  - BACKGROUND: Identification of a bacterial protein's subcellular localization
      (SCL) is important for genome annotation, function prediction and drug or vaccine
      target identification. Subcellular fractionation techniques combined with recent
      proteomics technology permits the identification of large numbers of proteins
      from distinct bacterial compartments. However, the fractionation of a complex
      structure like the cell into several subcellular compartments is not a trivial
      task. Contamination from other compartments may occur, and some proteins may
      reside in multiple localizations. New computational methods have been reported
      over the past few years that now permit much more accurate, genome-wide analysis
      of the SCL of protein sequences deduced from genomes. There is a need to compare
      such computational methods with laboratory proteomics approaches to identify the
      most effective current approach for genome-wide localization characterization and
      annotation. RESULTS: In this study, ten subcellular proteome analyses of
      bacterial compartments were reviewed. PSORTb version 2.0 was used to
      computationally predict the localization of proteins reported in these
      publications, and these computational predictions were then compared to the
      localizations determined by the proteomics study. By using a combined approach,
      we were able to identify a number of contaminants and proteins with dual
      localizations, and were able to more accurately identify membrane subproteomes.
      Our results allowed us to estimate the precision level of laboratory subproteome
      studies and we show here that, on average, recent high-precision computational
      methods such as PSORTb now have a lower error rate than laboratory methods.
      CONCLUSION: We have performed the first focused comparison of genome-wide
      proteomic and computational methods for subcellular localization identification,
      and show that computational methods have now attained a level of precision that
      is exceeding that of high-throughput laboratory approaches. We note that analysis
      of all cellular fractions collectively is required to effectively provide
      localization information from laboratory studies, and we propose an overall
      approach to genome-wide subcellular localization characterization that
      capitalizes on the complementary nature of current laboratory and computational
      methods.

PMID- 16288667
TI  - Our evolving understanding of 22q.11 deletion syndrome.

PMID- 16288668
TI  - Early motor development in young children with 22q.11 deletion syndrome and a
      conotruncal heart defect.
AB  - Velocardiofacial syndrome is identified by a submicroscopic deletion of
      chromosome 22q.11 (del22q.11). This study presents data on the early motor
      development and behaviour of 11 children (8 males, 3 females) with del22q.11
      (mean age 41mo, SD 9.7mo) with a congenital heart defect. To control for the
      impact of the congenital heart defect, a control group of 19 children (15 males,
      4 females; mean age 46mo, SD 9mo) with the same types of congenital heart defects
      but without del22q.11 was selected. Motor development in both groups was measured
      with the Peabody Developmental Motor Scales-2. Behaviour was assessed with the
      Child Behaviour Checklist. Children with del22q.11 scored significantly lower
      (p<0.05) on motor performance than the children of the control group. Most
      deficient motor skills were found for the subtests Locomotion and Stationary. On
      the behaviour questionnaire, a statistically significant (p<0.05) difference
      between the two groups was found only for the subscale Withdrawn. These data
      reveal a significant motor delay in many young children with del22q.11, which is
      not caused by the presence of a congenital heart defect or by behavioural
      features.

PMID- 16288670
TI  - Neuroimpairments, activity performance, and participation in children with
      cerebral palsy mainstreamed in elementary schools.
AB  - Participation and activity performance (motor and cognitive or behavioural) were
      examined in 148 children with cerebral palsy (CP; 87 males, 61 females; mean age
      9y 8mo, SD 1y 11mo; range 6y 1mo to 13y 7mo), mainstreamed in fully inclusive
      (n=100) and in self-contained classes (n=48) within general schools in Israel,
      using the School Function Assessment. Differences in participation within these
      groups were analyzed in relation to the type of CP (mainly spastic hemiplegia,
      spastic diplegia, and spastic tetraplegia), the level of impairment according to
      the Gross Motor Function Classification System (GMFCS; level II 55%, level III
      37%, and level IV 8%), and additional neuroimpairments. Univariate analyses of
      variance revealed significant differences in levels of participation and levels
      of activity performance between different types of CP and GMFCS levels. With
      regard to additional neuroimpairments, significant differences in participation
      were found for fully included children with speech and language impairments and
      those with learning disability within the self-contained group. Physical activity
      performance partly accounted for differences in participation between children
      with different types of CP and different levels of motor impairment. These
      findings suggest that within the mainstreamed environment, participation and
      activity performance increase as motor disability and/or additional
      neuroimpairments (speech and language impairments and learning disability)
      decrease.

PMID- 16288669
TI  - Attention deficits in children with 22q.11 deletion syndrome.
AB  - This study examined attention abilities of children with 22q.11 deletion
      syndrome. Thirty children (14 males, 16 females; age range 7 to 13y) were given
      comprehensive neuropsychological and neuropsychiatric assessments. Learning
      disability was found in 13 children. Superiority in verbal over performance IQ
      was very common. Attention-deficit-hyperactivity disorder (mainly of inattentive
      subtype) was diagnosed in 13 children. There appeared to be a relation between
      low IQ and presence of autism spectrum problems. The presence of attention
      deficits was clearly supported by the scores on the Child Behavior Checklist and
      the Conners Questionnaire. On the Becker attention tests the reaction times were
      significantly longer in the two visual and auditory tests, indicating that the
      ability to sustain attention is critically impaired in this group. A tendency of
      inferiority on auditory compared with visual tests was noted but there were no
      specific problems with the focus-execute aspect of attention.

PMID- 16288671
TI  - Neurodevelopmental implications of ocular motor apraxia.
AB  - Ocular motor apraxia (OMA), a disorder of saccadic initiation, may be congenital
      or acquired. While the acquired form is frequently associated with significant
      neuropathology, the congenital form is often regarded as relatively benign. Many
      children with congenital OMA who were observed clinically have shown
      neurodevelopmental disturbance over time. A retrospective review was taken of 34
      consecutive patients (22 males and 12 females), seen over a 20-year period, to
      evaluate the frequency and type of associated neurodevelopmental problems. Age at
      presentation ranged from 8 weeks to 14 years, with a mean age of 10 years. Of 29
      children with congenital OMA, 15 had imaging evidence of structural central
      nervous system abnormalities (with cerebellar hypoplasia the most frequent
      abnormality detected). Eleven of the 14 patients with no structural abnormality
      showed abnormal neurodevelopment. This study suggests that congenital OMA is not
      a benign diagnosis, even in the absence of overt neurological disturbance at the
      time of presentation.

PMID- 16288672
TI  - Stability of the Bayley II Scales of Infant Development in a sample of low-risk
      and high-risk infants.
AB  - The aim of this study was to examine the stability of the second edition of the
      Bayley Scales of Infant Development (Bayley II) by correlating Bayley II scores
      during the first year of life with Bayley II scores at approximately 18 months of
      age. Bayley II Mental and Motor Scales were administered to 119 infants (69
      males, 50 females) during their first year of life; mean age for low-risk group 7
      months (SD 3.01) and mean age for high-risk group 7.8 months (SD 2.46). A second
      set of Bayley II scores was collected on 104 of the infants at 17 to 22 months of
      age; mean age for low-risk group 18.5 months (SD 1.07) and mean age for high-risk
      group 18.9 months (SD 1.11). Mean time interval between the two assessments was
      11.5 months for the low-risk group and 11.15 months for the high-risk group.
      Stability of the scores over time was assessed. Correlations for the Bayley II
      Mental Developmental Index and Psychomotor Developmental Index between
      administrations during the first and second years of life were r=0.49 (p<0.001)
      and r=0.48 (p<0.001) respectively. We conclude that approximately 23 to 24% of
      the variance in the infants' later Bayley II scores could be explained by the
      earlier scores. This is one of only two studies to examine the stability of
      Bayley II over time. Replication studies are needed to evaluate the consistency
      of these findings across other samples of infants.

PMID- 16288673
TI  - Intellectual decline in children with moyamoya and sickle cell anaemia.
AB  - Intelligence is reported to decline after onset of moyamoya in Japanese
      populations, but there is less evidence for this in Western populations where the
      condition may be secondary to stroke and sickle cell anaemia (SCA). Preoperative
      longitudinal IQ data were obtained from 15 children (seven males, eight females)
      who developed moyamoya syndrome (MMS) following a stroke (six with SCA, nine
      without SCA), and 19 controls (10 males, nine females; nine healthy control
      participants, 10 with SCA). At baseline assessment (Time 1) median age of
      patients was 7 years 6 months (range 3y 7mo to 12y 5mo); median age of controls
      was 6 years 3 months (range 4y to 11y 6mo). At follow-up (Time 2), ages were 11
      years 8 months (range 3y 7mo to 12y 5mo) and 12 years 8 months (range 6y 4mo to
      16y 8mo) in patients and controls respectively. Median duration of follow-up for
      the patient group was 3 years (range 7 to 10y) and in controls, 4 years 1 month
      (range 1 to 10y). In children with SCA, Verbal and Performance IQs (VIQ and PIQ)
      were significantly lower than in controls at Time 1; there was an additional
      independent statistically significant reduction in PIQ associated with MMS
      (p=0.004). Although there were further significant reductions in IQ by the second
      assessment for patients with MMS compared with controls, IQ did not differ
      significantly between groups with and without SCA. While the reduction in IQ
      attributed to SCA does not appear to become more marked with increasing age, the
      difference between those with and without MMS is associated with increasing
      effect over time.

PMID- 16288674
TI  - Atypical case of hemiconvulsions-hemiplegia-epilepsy syndrome revealing
      contralateral focal cortical dysplasia.
AB  - Hemiconvulsions-hemiplegia-epilepsy syndrome (HH/HHE) is a rare epileptic
      syndrome consisting of a prolonged unilateral convulsion producing a persisting
      hemiplegia, sometimes followed by epilepsy. We report on a 13-month-old male who
      presented with febrile left-sided HH syndrome with right hemispheric unilateral
      cytotoxic oedema followed by hemispheric atrophy on magnetic resonance imaging
      (MRI). Six months later the child progressively developed refractory focal
      epilepsy, including right hemiclonic seizures, and nearly continuous left frontal
      rhythmic spikes, suggesting the presence of a focal cortical dysplasia (FCD). A
      repeat MRI at 2 years of age showed left frontal FCD. This unusual case of dual
      pathology--right HH syndrome and left FCD--suggests that some other factor than
      the malformation determined the prolonged status and brain atrophy. The kinetics
      of regional cortical maturation could explain this unusual condition.

PMID- 16288675
TI  - Muscle biopsy without centrally located nuclei in a male child with mild X-linked
      myotubular myopathy.
AB  - In children with a myopathy, muscle biopsy, together with the clinical
      presentation, can guide further investigations. The presence of centrally located
      nuclei suggests a myotubular myopathy, and gene testing may confirm this
      diagnosis. We describe a male child with a mild form of X-linked myotubular
      myopathy for which repeated muscle biopsy did not show the characteristic pattern
      of centrally located nuclei. Myotubular myopathy was not contemplated, therefore,
      until a maternally related relative was shown to have the disorder. Genetic
      testing showed that the index case carried the same mutation in his MTM1 gene as
      this relative.

PMID- 16288676
TI  - Aquatic exercise for children with cerebral palsy.
AB  - Exercise for children with cerebral palsy (CP) is gaining popularity among
      pediatric physical therapists as an intervention choice. Exercise in water
      appeals to children with CP because of the unique quality of buoyancy of water
      that reduces joint loading and impact, and decreases the negative influences of
      poor balance and poor postural control. In this paper, research of land-based
      exercise and aquatic exercise for children with CP is reviewed. Clinically
      relevant considerations for aquatic exercise programming for children with CP are
      discussed.

PMID- 16288677
TI  - Seeing the mind: considerations on visual metaphors of the mind in Western
      thought (16th-18th centuries).
AB  - Throughout the centuries, in Western culture, scientists, philosophers, and
      artists have been fascinated by the working of the mind. They have attempted to
      translate this into visual models that are able to provide tangible references to
      otherwise abstract concepts. These metaphors are deeply rooted in culture and
      their significance encompasses ideas which shape and characterize different
      epochs. With a consideration of visual models of the mind developed in Western
      thought during the 16th and 18th centuries, this article aims to provide an
      overview of some of the most significant metaphors developed to illustrate the
      working of the mind and highlight their broader cultural significance. Generally,
      models used to describe the brain, and consequently to conceptualize the mind,
      match the most recent technical achievements or important cultural developments.
      They illustrate the processes through which material reality and the self are
      perceived and represented. This article shows how these models betray broader
      cultural concerns and testify to the zeitgeist of an epoch.

PMID- 16288679
TI  - Measuring spiritual belief: development and standardization of a Beliefs and
      Values Scale.
AB  - BACKGROUND: Higher levels of religious involvement are modestly associated with
      better health, after taking account of other influences, such as age, sex and
      social support. However, little account is taken of spiritual beliefs that are
      not tied to personal or public religious practice. Our objective was to develop a
      standardized measure of spirituality for use in clinical research. METHOD: We
      characterized the core components of spirituality using narrative data from a
      purposive sample of people, some of whom were near the end of their lives. These
      data were developed into statements in a scale to measure strength of spiritual
      beliefs and its reliability, validity and factor structure were evaluated in
      order to reach a final version. RESULTS: Thirty-nine people took part in the
      qualitative study to define the nature of spirituality in their lives. These data
      were used to construct a 47-item instrument that was evaluated in 372 people
      recruited in medical and non-medical settings. Analysis of these statements led
      to a 24-item version that was evaluated in a further sample of 284 people
      recruited in similar settings. The final 20-item questionnaire performed with
      high test-retest and internal reliability and measures spirituality across a
      broad religious and non-religious perspective. CONCLUSIONS: A measure of
      spiritual belief that is not limited to religious thought, may contribute to
      research in psychiatry and medicine.

PMID- 16288680
TI  - Prevalence and genetic and environmental influences on anxiety disorders in 6
      year-old twins.
AB  - BACKGROUND: Prevalence of childhood anxiety disorders at specific ages and
      genetic etiological influences on anxiety disorders in young children have been
      little studied. The present study reports prevalence estimates in a community
      sample of 6-year-old twins, and patterns of genetic and environmental influences
      on these early-onset anxiety disorders. METHOD: Using a two-phase design 4,662
      twin-pairs were sampled and 854 pairs were assessed in the second phase by
      maternal-informant diagnostic interview using DSM-IV criteria. RESULTS: The most
      common conditions were separation anxiety disorder (SAD) [2.8%, 95% confidence
      interval (CI) 2.1-3.8, for current disorder] and specific phobia (10.8%, 95% CI
      8.4-13.6, for current disorder). Behavioral genetic modeling was feasible for
      these two conditions, applied to two phenotypes: symptom syndrome (regardless of
      impairment) and the narrower one of diagnostic status (symptom syndrome with
      associated impairment). The heritability estimate for SAD diagnostic status was
      high, 73%, with remaining variance attributed to non-shared environment. The
      heritability estimates for specific phobia were also high, 80% for the symptom
      syndrome and 60% for diagnostic status, with remaining variance attributed in
      both cases to non-shared environment. CONCLUSIONS: Compared with previous
      epidemiological surveys of children and adolescents in wide age-bands, the
      current estimates suggest that rates of anxiety disorders assessed in young
      childhood are generally at least as high and perhaps higher compared with those
      found in older children. The heritability estimates suggest that the genetic
      effects on these early-onset anxiety disorders are substantial and more
      significant than environmental effects, whether shared or non-shared.

PMID- 16288681
TI  - The antipsychotic sultopride is overdosed--a PET study of drug-induced receptor
      occupancy in comparison with sulpiride.
AB  - Conventional antipsychotics tend to elicit extrapyramidal symptoms at clinical
      doses, but dose optimization could reduce the risk of such side-effects. In-vivo
      receptor-binding studies have suggested that 70-80% of dopamine D2 receptor
      occupancy provides the desired antipsychotic effects without extrapyramidal
      symptoms. In terms of dose optimization based on the occupancy, there has not
      been enough supporting data regarding the clinical doses of the respective
      antipsychotics. In this study, we measured dopamine D2 receptor occupancy of two
      conventional benzamide antipsychotics, sulpiride and sultopride, using positron
      emission tomography, to investigate the rationale of their clinical dose.
      Although they are prescribed at similar doses (300-1200 mg), the doses required
      to obtain similar receptor occupancy (70-80%) were quite different: 1010-1730 mg
      for sulpiride but 20-35 mg for sultopride. In terms of dose, sultopride has about
      50 times greater potency than sulpiride based on dopamine D2 receptor occupancy.
      Evidence for the optimal doses of conventional antipsychotics based on dopamine
      D2 receptor occupancy would be helpful for rational antipsychotic therapy.

PMID- 16288682
TI  - Duloxetine in the treatment of panic disorder.

PMID- 16288683
TI  - Detection of intra-familial transmission of shigella infection using conventional
      serotyping and pulsed-field gel electrophoresis.
AB  - Pulsed-field gel electrophoresis (PFGE) is commonly used in molecular
      epidemiology. However, this technique has never been used in studying intra
      family spread of enteric diseases in Bangladesh. Our objective was to evaluate
      the intra-familial transmission of shigella infection using PFGE. Children of
      either sex, less than 10 years old, who were family contacts of shigella-infected
      index cases were the study population. PFGE was applied if the same serotypes/sub
      serotypes of shigella were isolated from both the index case and the family
      contact children. In total, 227 index cases were studied. Shigella was isolated
      from 61 (27%) contact children on day 1 of enrolment, among which Shigella
      flexneri (41%) and S. boydii (41%) were dominant, followed by S. dysenteriae
      (10%), S. sonnei (3%), and shigella-like organisms (5%). Seventeen (28%) of the
      asymptomatic infections in contact children were caused by the same serotype of
      shigella as that found in the index case. The intra-familial shigella
      transmission rate was 8% (17/227). Of the 227 contact children, eight (4%)
      developed diarrhoea during a 10-day follow-up and shigella was isolated from five
      (2%) of these children, and three of them (S. flexneri 3a, 1b, and 3a) were
      identical to the strains from their respective index cases. Compared to children
      without asymptomatic carriage of shigella (2/166), the risk (odds ratio) of
      developing diarrhoea for the children with asymptomatic carriage of shigella
      identical to their cases (3/17) was 9.0 (95% CI 1.5-49.0, P=0.01). The
      attributable risk for symptomatic shigella infection by intra-familial
      transmission was 50%. Results of this study demonstrated that intra-familial
      transmission of shigella carries a higher risk for diarrhoea.

PMID- 16288684
TI  - Changes in the epidemiology of epiglottitis following introduction of Haemophilus
      influenzae type b (Hib) conjugate vaccines in England: a comparison of two data
      sources.
AB  - Paediatric cases of epiglottitis declined markedly in England following the
      introduction of safe effective immunization against Haemophilus influenzae type b
      (Hib). With the recently described resurgence in Hib infections, a corresponding
      rise in the number of presentations of clinical epiglottitis in children was
      observed, although numbers were still well below those reported prior to vaccine
      availability. This was seen both in microbiology reports and hospital admissions
      data for England. In keeping with the more diverse aetiology of epiglottitis in
      adults, Hib vaccination had minimal impact on hospital presentations with upper
      airway infections in those aged 15 years and over, which showed an overall
      increasing trend over 10 years. The need for a high index of suspicion to allow
      early diagnosis of this life-threatening clinical presentation is reinforced.

PMID- 16288685
TI  - Outbreak of early syphilis in an institution for the care of adults with mental
      disorders.
AB  - This paper describes the features of an outbreak of early syphilis in an
      institution for the care of adults with mental disorders. A case-note review was
      performed. In the period June to November 2001, 87 cases of syphilis were
      diagnosed [25 primary, 21 secondary and 41 early latent syphilis in 983 inmates
      (crude attack rate 8.9%)]. Among them 82 were heterosexual, four were homosexual
      or bisexual, and for one case sexual preference was not established. About half
      the cases were known to be promiscuous. The initial case was not identified.
      Penicillin therapy was administered to all cases and all known or suspected
      sexual contacts. Sporadic cases of syphilis have, however, continued to emerge
      from time to time. Institutions for patients with mental disorders are vulnerable
      to sexually transmitted diseases, and special strategies should be devised for
      their control.

PMID- 16288686
TI  - Risk factors for typhoid fever among adult patients in Diyarbakir, Turkey.
AB  - We conducted a case-control study to assess risk factors for typhoid fever in
      Diyarbakir, Turkey, a region where transmission of Salmonella typhi is endemic.
      We prospectively identified febrile patients from Diyarbakir and the surrounding
      area who were admitted to hospital. Cases were defined as patients who had S.
      typhi isolated from at least one blood culture. Sixty-four cases with blood
      culture-confirmed S. typhi were identified between May 2001 and May 2003. In
      total, 128 age- and sex-matched controls selected from neighbourhoods as cases
      were enrolled. We hypothesized that consumption of raw vegetables contaminated
      with sewage would be associated with an increased risk of typhoid fever.
      Conditional logistic regression modelling revealed that living in a crowded
      household (OR 3.31, 95% CI 1.58-6.92, P=0.002), eating cig kofte (a traditional
      raw food) (OR 5.29, 95% CI 2.20-12.69, P=0.000) and lettuce salad (OR 3.55, 95%
      CI 1.52-8.28, P=0.003) in the 15 days prior to symptoms onset was independently
      associated with typhoid fever. We conclude that living in a crowded household and
      consumption of raw vegetables outside the home increase the risk of typhoid fever
      in this region.

PMID- 16288690
TI  - Irritating experiments. Haller's concept and the European controversy on
      irritability and sensibility, 1750-90.

PMID- 16288700
TI  - Adverse events at the aneurysmal neck identified at follow-up after endovascular
      abdominal aortic aneursym repair: how do they correlate?
AB  - The objective of this study was to assess the prevalence of and the correlation
      between dilatation of the infrarenal neck and proximal device migration after
      endovascular abdominal aortic aneurysm repair (EVAR). The analysis made use of
      the EUROSTAR registry. Between 1994 and 2004, 4,233 patients with an abdominal
      aortic aneurysm larger than 4 cm underwent EVAR. Only patients with available
      follow-up data regarding neck size and device position were included in this
      assessment. Chi-square and t-tests or Wilcoxon rank sum tests were used for
      comparison of discrete and continuous variables, respectively. Time-dependent
      variables were evaluated by log-rank tests. In addition, multivariate analysis
      was performed to determine anatomic and operative variables with an independent
      correlation with neck growth and device migration, respectively. In addition, the
      association with proximal endoleak was assessed. Neck dilatation and proximal
      migration were found in 1,342 (32%) and 192 (4.5%) of the 4,233 patients,
      respectively. One hundred twelve patients (2.5%) had neck dilatation and
      migration of the proximal device extremity. The correlation between proximal
      migration and neck dilatation was statistically significant (p < .0001). Other
      independent variables for migration were a wider neck and aneurysmal diameter,
      shorter necks, proximal endoleak, and absence of suprarenal fixation. Neck
      dilatation was predicted by narrow necks, use of devices with suprarenal
      fixation, and larger device diameters. Proximal endoleak occurred in 136 (3.2%)
      patients and was significantly associated with shorter, angulated necks and
      proximal migration. The present study documented that migration may be caused by
      neck dilatation. However, neck dilatation was not significantly promoted by
      proximal migration. Other factors, such as dimensions of the neck, the device
      fixation system, and perhaps progressive wall degeneration, are also likely to
      play a role in the pathogenesis of neck dilatation. To obtain good results from
      EVAR, accepted criteria of neck dimensions should be adhered to.

PMID- 16288701
TI  - Utility of basilic vein transposition for dialysis access.
AB  - Autologous arteriovenous access is the key to long-term success with hemodialysis
      and is strongly supported by the National Kidney Foundation's Dialysis Outcomes
      Quality Initiative guidelines. Basilic vein transposition (BVT) fulfills the need
      for a durable conduit with high patency and maturation rates. This retrospective
      review examines a single group's experience with this procedure. All patients
      undergoing BVT for hemodialysis with available follow-up data were reviewed.
      Telephone interviews were used to supplement clinical data where needed.
      Functional assisted patency was used as the end point for this procedure, and if
      the access was never used for dialysis, then the patency was considered zero.
      Secondary interventions performed while the access remained patent and in use
      were not considered detrimental to the patency reported. One hundred seventy BVTs
      in 162 patients were performed between November 1992 and October 2001. There were
      87 women (53.7%) and 112 black patients (69.1%); hypertension was present in 138
      patients (85.2%) and diabetes in 89 patients (54.9%). Each year, an increasing
      incidence of BVT was performed in our dialysis population. The BVT was performed
      as the first access in that extremity in 73 of the procedures (42.9%). Functional
      patency (primary assisted) was achieved in 40.0% at 2 years and 15.2% at 5 years.
      The mean assisted patency was 14.6 months. To maintain BVT patency, 40
      percutaneous secondary interventions (69.0%) and 18 surgical revisions (31.0%)
      occurred in 32 patients (19.0%). Ligation for swelling was necessary in 4
      patients (2.5%), and steal syndrome occurred in 3 patients (1.9%). BVT is a
      useful autologous procedure for hemodialysis and the preferred access alternative
      in patients without an adequate cephalic vein. Although patencies remain poor
      relative to other conventional arterial vascular procedures, BVT is our most
      durable hemodialysis access procedure and is often the only available autologous
      conduit for hemodialysis.

PMID- 16288702
TI  - Abdominal aortic aneurysm repair in octogenarians versus younger patients in a
      tertiary referral center.
AB  - Operative survival is as high as 96% for elective abdominal aortic aneursym (AAA)
      repair but as low as 10% for emergency repair. Our primary aim was to compare
      elective AAA repair in octogenarians with nonoperative management. Our secondary
      aim was to compare octogenarians with their younger counterparts. From 1998 to
      2003, 180 patients with AAA were treated operatively or nonoperatively. Factors
      determining treatment included American Society of Anesthesiologists grade >or=
      4, inoperable malignancy, New York Heart Association class III, forced expiratory
      volume in 1 second < 35%, creatinine > 6.0 mg/dL, and patient and family choice.
      A parallel-group observational study was performed to assess age and treatment
      effects on outcome. Seventy (39%) patients were repaired electively, 68 (38%)
      were managed nonoperatively, and 42 (23%) underwent emergency repair. Fifty-nine
      (33%) were octogenarians. The octogenarian 5-year survival rate was 20% following
      emergency repair, 42% if treated nonoperatively, and 83% following elective
      repair. Younger cohort rates were 55% (emergency), 44% (nonoperative), and 76%
      (elective). The octogenarian mean expansion rate was 0.26 cm/yr in those treated
      nonoperatively and 1.04 cm/yr in confirmed rupture. Rupture rate was related to
      expansion rate (95% confidence interval [CI] 0.06-0.59, r = .35, p = .01). The
      rates in the younger subgroup were 0.32 cm/yr and 1.14 cm/yr (95% CI -0.021
      0.672}, r = .37, p = .03). The octogenarian survival rate was highest following
      elective repair. Rupture was closely correlated with aneurysm expansion.
      Screening should reduce the incidence of octogenarian rupture of AAA and identify
      those patients most suitable for nonoperative management.

PMID- 16288703
TI  - OptEase retrievable inferior vena cava filter: initial multicenter experience.
AB  - The purpose of this article is to describe our experience with the retrievable
      OptEase inferior vena cava filter (IVCF) (Cordis Corporation, Miami Lakes, FL) in
      the prevention of pulmonary embolus (PE). Forty patients (24 men, age range 15-85
      years, mean age 38 years) who were at temporary risk of PE underwent insertion
      and retrieval of the OptEase IVCF at two institutions. Eleven patients were
      treated with filter implantation and subsequent repositioning in the inferior
      vena cava (IVC) to extend implantation time. All patients were followed up for 24
      hours after retrieval, with additional follow-up at the physician's discretion.
      Forty patients had successful filter insertion. Two patients who underwent
      intravascular ultrasound guidance for filter deployment required filter
      repositioning within 24 hours owing to inadvertent placement in the right common
      iliac vein. All 40 patients underwent successful filter retrieval with no adverse
      events. In those patients who did not undergo IVCF repositioning, the time to
      retrieval ranged from 3 to 48 days (mean +/- SD 16.38 +/- 7.20 days). One patient
      had a successful retrieval at 48 days, but all other retrieval experiences were
      performed within 23 days. The second strategy involved implantation, with
      repositioning at least once before final retrieval. This latter strategy occurred
      in 11 patients, and the time to first capture ranged from 4 to 30 days (mean +/-
      SD 13.82 +/- 6.13 days). No symptomatic PE, IVC injury or stenosis, significant
      bleeding, filter fracture, or filter migration was observed. In this feasibility
      study, the OptEase IVCF prevented symptomatic PE, was safely retrieved or
      repositioned up to 48 days after implantation, and served as an effective bridge
      to anticoagulation. In patients who require extended IVCF placement, the OptEase
      IVCF can be successfully repositioned within the IVC, thereby extending the
      overall implantation time of this retrievable IVCF.

PMID- 16288704
TI  - Matrix metalloproteinases in the aneurysm wall of patients treated with low-dose
      doxycycline.
AB  - The purpose of this study was to determine the effect of low-dose doxycycline on
      matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP)-1
      expression in the wall of abdominal aortic aneurysms. A double-blind, randomized
      study was conducted of patients treated with doxycycline (100 mg/d orally) or
      placebo for 1 month prior to surgery. MMP-2, -3, and -9 (zymogen and activity);
      MMP-1, -2, -3, -7, -9, -11, -12, and -14; and TIMP-1 (messenger ribonucleic acid
      [mRNA]) were measured in the aneurysm wall. No differences were found between the
      treatment and placebo groups in zymogen levels of MMP-2, -3, or -9 or in the free
      or total activities of MMP-2 and -9. Treatment with doxycycline also had no
      effect on the concentration of any mRNA measured. No relationship was found
      between the number of tablets taken and MMP or TIMP protein, mRNA, or activity
      levels in the aneurysm wall. Low-dose doxycycline treatment does not alter the
      expression or activity of metalloproteinases or their inhibitor, TIMP-1, in the
      aneurysm wall.

PMID- 16288705
TI  - Aortic arch aneurysm and patent left internal mammary artery: technique of
      transposition of supra-aortic vessels and embolization of the subclavian artery.
AB  - Endovascular treatment of aortic arch aneurysms poses unique problems because of
      vascularization of the carotid arteries. Transposition of supra-aortic vessels is
      becoming an established and accepted strategy for expanding the applicability of
      stent graft repair. left subclavian artery (LSA) is not usually transposed
      because its overstenting does not produce relevant complications. Nevertheless,
      some selected cases need high-pressure revascularization of the LSA, such as in
      the presence of a patent left internal mammary artery. We present a technique of
      revascularization of supra-aortic vessels and "balloon protected" embolization of
      the origin of the LSA.

PMID- 16288706
TI  - Use of N-acetylcholine and sodium bicarbonate to protect renal transplant
      function during endovascular renal artery aneurysm exclusion.
AB  - We describe the successful use of hydration with sodium bicarbonate and N
      acetylcholine to prevent contrast-induced nephrophathy in a patient with a kidney
      transplant undergoing endovascular native renal artery aneurysm exclusion. The
      implications for surveillance studies for endovascular procedures are discussed.

PMID- 16288707
TI  - Aortoduodenal fistula after abdominal aortic stent graft presenting with
      extremity abscesses.
AB  - Aortoenteric fistula (AEF) has been described after endovascular stent graft
      repair of abdominal aortic aneurysms (EVAR). AEF after EVAR has been associated
      with aneurysm growth, endoleak, migration, and aortic inflammation. We report a
      patient with an AEF presenting 2 years after EVAR with two abscesses in the right
      leg. A computed tomographic scan showed a gas-filled thrombus lining the right
      limb of his graft. At conversion, no endoleak, device migration, or residual
      aneurysm sac was found. AEF can occur after endoluminal stent graft (ELG) in the
      absence of aneurysm growth, endoleak, migration, or inflammation. AEF can cause
      ELG infection and extremity infection.

PMID- 16288708
TI  - Popliteal traumatic arteriovenous fistula.
AB  - Popliteal trauma requires particular attention because blood vessel injuries in
      that zone might cause serious complications. Popliteal traumatic arteriovenous
      fistula (AVF) should be considered for serious leg amputation, and long-standing
      fistulae produce cardiac overload. The diagnosis is usually made after clinical
      examination, finding palpable thrill and audible bruit over the injury site, and
      is confirmed after duplex ultrasonography and/or angiography. We present a case
      of popliteal traumatic arteriovenous fistula with false aneurysm (pseudoaneurysm)
      (PSA), in which duplex ultrasonography and angiography findings proved
      inconsistent with the findings at surgery, thus resulting in an unnecessary
      extensive dissection of a major artery and vein, whereas the fistula and the PSA
      were found in minor vessels (genicular artery and vein).

PMID- 16288709
TI  - Endoluminal recanalization in a patient with phlegmasia cerulea dolens using a
      multimodality approach.
AB  - Phlegmasia cerulea dolens, a rare complication of deep venous thrombosis, has
      traditionally been difficult to treat. The patient described in this report posed
      additional therapeutic challenges based on a history of heparin-induced
      thrombocytopenia. She presented with severe leg pain and swelling, and a venogram
      showed occlusion of both her inferior vena cava and right iliac vein. The use of
      a multimodality approach, both chemical and mechanical, was successful in
      removing the venous occlusion, thereby preventing further complications, such as
      circulatory shock, postphlebitic syndrome, and venous gangrene.

PMID- 16288710
TI  - Bayesian methodology incorporating expert judgment for ranking countermeasure
      effectiveness under uncertainty: example applied to at grade railroad crossings
      in Korea.
AB  - Transportation professionals are sometimes required to make difficult
      transportation safety investment decisions in the face of uncertainty. In
      particular, an engineer may be expected to choose among an array of technologies
      and/or countermeasures to remediate perceived safety problems when: (1) little
      information is known about the countermeasure effects on safety; (2) information
      is known but from different regions, states, or countries where a direct
      generalization may not be appropriate; (3) where the technologies and/or
      countermeasures are relatively untested, or (4) where costs prohibit the full and
      careful testing of each of the candidate countermeasures via before-after
      studies. The importance of an informed and well-considered decision based on the
      best possible engineering knowledge and information is imperative due to the
      potential impact on the numbers of human injuries and deaths that may result from
      these investments. This paper describes the formalization and application of a
      methodology to evaluate the safety benefit of countermeasures in the face of
      uncertainty. To illustrate the methodology, 18 countermeasures for improving
      safety of at grade railroad crossings (AGRXs) in the Republic of Korea are
      considered. Akin to "stated preference" methods in travel survey research, the
      methodology applies random selection and laws of large numbers to derive accident
      modification factor (AMF) densities from expert opinions. In a full Bayesian
      analysis framework, the collective opinions in the form of AMF densities (data
      likelihood) are combined with prior knowledge (AMF density priors) for the 18
      countermeasures to obtain 'best' estimates of AMFs (AMF posterior credible
      intervals). The countermeasures are then compared and recommended based on the
      largest safety returns with minimum risk (uncertainty). To the author's knowledge
      the complete methodology is new and has not previously been applied or reported
      in the literature. The results demonstrate that the methodology is able to
      discern anticipated safety benefit differences across candidate countermeasures.
      For the 18 at grade railroad crossings considered in this analysis, it was found
      that the top three performing countermeasures for reducing crashes are in-vehicle
      warning systems, obstacle detection systems, and constant warning time systems.

PMID- 16288711
TI  - Cell expression of MMP-1 and TIMP-1 in co-cultures of human gingival fibroblasts
      and monocytes: the involvement of ICAM-1.
AB  - Matrix metalloproteinase-1 (MMP-1) plays an important role in the degradation of
      collagen in inflammatory diseases. The aim of this study was to investigate the
      cellular expression of MMP-1 and its inhibitor, tissue inhibitor of
      metalloproteinase-1 (TIMP-1), in gingival fibroblasts co-cultured with monocytes
      and the possible mediating role of intercellular adhesion molecule-1 (ICAM-1). In
      co-cultures, the expression of MMP-1 and TIMP-1 increased in fibroblasts, but not
      in monocytes, although the number of MMP-1+ and TIMP-1+ adhered monocytes
      increased. Moreover, ICAM-1 expression in both fibroblasts and adhered monocytes
      increased. In the presence of an anti-ICAM-1 antibody, the expression of MMP-1 in
      fibroblasts decreased whereas the number of TIMP-1+ adhered monocytes increased.
      The p38 MAPK inhibitor SB203580 reduced MMP-1 expression in fibroblasts, as well
      as ICAM-1 expression in both fibroblasts and adhered monocytes. The results
      suggest that co-culture with monocytes enhances cellular expression of MMP-1 and
      TIMP-1 in gingival fibroblasts, and that the increased MMP-1 expression, in
      contrast to TIMP-1, is partly mediated by the adhesion molecule ICAM-1 and the
      p38 MAPK signal pathway.

PMID- 16288712
TI  - Detection of Bax protein conformational change using a surface plasmon resonance
      imaging-based antibody chip.
AB  - We describe an antibody chip technology that uses a surface plasmon resonance
      (SPR) imaging system to examine the conformational change of a protein. In this
      study, we used Bax protein, a pro-apoptotic member of the Bcl-2 family of
      proteins, as a model protein to investigate the conformational alteration
      triggered by a TNF-related apoptosis-inducing ligand (TRAIL), a potent inducer of
      apoptosis. To develop the antibody chip for detecting the Bax conformational
      change, we immobilized Bax monoclonal antibody 6A7, which recognizes only a
      conformationally changed Bax protein on a gold surface. The resultant immobilized
      Bax antibodies provided specific and accurate measurements of the active
      conformation-specific epitope in the apoptotic cancer cells treated with the
      TRAIL; these measurements corresponded to the data obtained by
      immunoprecipitation analysis using an active conformation-specific Bax antibody
      (6A7). The results of our study indicated that TRAIL-induced Bax structural
      change could be monitored quickly and simply using an SPR imaging system, thus
      demonstrating the potential for using such a system for the analysis of
      conformational properties of target proteins.

PMID- 16288713
TI  - Interaction of recombinant human eIF2 subunits with eIF2B and eIF2alpha kinases.
AB  - The heterotrimeric eukaryotic initiation factor 2 (eIF2) plays a critical role in
      the mechanics and regulation of protein synthesis. Unlike yeast and archaeal
      eIF2, the purified baculovirus-expressed recombinant human eIF2 subunits used in
      these studies reveal that the alpha- and beta-subunits interact with each other.
      Consistent with this observation, the beta-subunit specifically interacts with
      the purified eIF2B in ELISA studies and this interaction is enhanced when wt
      eIF2alpha in the recombinant trimeric complex is phosphorylated or replaced by a
      mutant phosphomimetic eIF2alpha (S51D). These findings together with other
      observations raise the possibility that the beta-subunit plays a key role in the
      regulation and function of mammalian eIF2 complex. PERK, an eIF2alpha kinase, is
      found to interact with wt and mutants of eIF2alpha in which the serine 51 or 48
      residue is replaced by alanine or aspartic acid thereby suggesting that the
      phosphorylation site in the substrate is not important for interaction.
      Fluorescence spectroscopic and fluorescence resonance energy transfer analyses
      reveal that the energy transfer occurs from PERK to eIF2alpha. The dissociation
      constant of alpha-subunit-PERK complex (Kd alpha-subunit) is 0.74 microM and the
      interaction is stoichiometric.

PMID- 16288714
TI  - TNF-related apoptosis-inducing ligand and its decoy receptor osteoprotegerin in
      nonischemic dilated cardiomyopathy.
AB  - Apoptosis has been attributed an essential role in dilated cardiomyopathy (DCM)
      recently. We assessed expression of TNF-related apoptosis-inducing ligand (TRAIL)
      and its decoy receptor osteoprotegerin (OPG) in men with nonischemic DCM, who
      underwent coronary angiography and endomyocardial biopsy (EMB) after exclusion of
      coronary artery disease compared to control patients. TRAIL plasma concentrations
      were elevated in DCM (p=0.02 vs. controls), and were positively correlated with
      left ventricular enddiastolic diameter (r=0.15, p=0.04), whereas OPG plasma
      levels did not differ between both groups (p=0.96). In EMB of DCM patients, TRAIL
      and OPG protein were detected by immunohistochemistry but not in controls.
      Furthermore, gene expression in EMB or peripheral blood leukocytes (PBL) of DCM
      patients assessed by real-time PCR showed an increase of TRAIL mRNA in PBL
      (p=0.01 vs. controls), whereas OPG mRNA was upregulated in endomyocardial
      specimens (p<0.001 vs. controls). In conclusion, myocardial overexpression of
      antiapoptotic OPG in DCM patients may represent a compensatory mechanism to limit
      systemic activation of TRAIL in patients with congestive heart disease.

PMID- 16288715
TI  - Alternative protein secretion: the Mam1 ABC transporter supports secretion of M
      factor linked GFP in fission yeast.
AB  - To examine whether the fission yeast Mam1 ABC transporter can be used for
      secretion of heterologous proteins, thereby bypassing the classical secretion
      pathway, we have analyzed chimeric forms of the M-factor precursor. It was
      demonstrated that GFP can be exported when fused to both the amino-terminal
      prosequence from mfm1 and a CaaX motif. This secretion was dependent on the Mam1
      transporter and not the classical secretion pathway. The secretion efficiency of
      GFP, however, was relatively low and most of the reporter protein was trapped in
      the vacuolar membranes. Our findings suggest that the Mam1 ABC protein is a
      promiscuous peptide transporter that can accommodate globular proteins of a
      relatively large size. Furthermore, our results help in defining the sequences
      required for processing and secretion of natural M-factor.

PMID- 16288716
TI  - Murine mesenchymal and embryonic stem cells express a similar Hox gene profile.
AB  - Using degenerate oligonucleotide primers targeting the homeobox domain, we
      amplified by PCR and sequenced 723 clones from five murine cell populations and
      lines derived from embryonic mesoderm and adult bone marrow. Transcripts from all
      four vertebrate Hox clusters were expressed by the different populations.
      Hierarchical clustering of the data revealed that mesenchymal stem cells (MSCs)
      and the embryonic stem (ES) cell line D3 shared a similar Hox expression profile.
      These populations exclusively expressed Hoxb2, Hoxb5, Hoxb7, and Hoxc4,
      transcripts regulating self-renewal and differentiation of other stem cells.
      Additionally, Hoxa7 transcript quantified by real-time PCR strongly correlated
      (r2=0.89) with the number of Hoxa7 clones identified by sequencing, validating
      that data from the PCR screen reflects differences in Hox mRNA abundance between
      populations. This is the first study to catalogue Hox transcripts in murine MSCs
      and by comparative analyses identify specific Hox genes that may contribute to
      their stem cell character.

PMID- 16288717
TI  - Immunization using an Apo B-100 related epitope reduces atherosclerosis and
      plaque inflammation in hypercholesterolemic apo E (-/-) mice.
AB  - Immune system modulates atherosclerosis and immunization using homologous LDL
      reduces atherosclerosis in hyperlipidemic animals. The nature of athero
      protective antigenic epitopes in LDL remains unclear. We have recently identified
      nearly a 100 antigenic epitopes in human apo B-100 and in this study we evaluated
      the effects of immunization with two such epitopes on atherosclerosis in
      hypercholesterolemic apo E (-/-) mice. Male apo E (-/-) mice were immunized at 6
      7 weeks of age with two different apo B-100 related peptide sequences using alum
      as adjuvant and mice immunized with alum alone served as controls. Peptide-2
      immunization reduced aortic atherosclerosis by 40% and plaque inflammation by 80%
      compared to controls without a reduction in circulating cholesterol levels
      whereas Peptide-1 immunization had no effect. Peptide-2 immunization also reduced
      the progression of aortic lesions when mice were immunized at 16 weeks of age,
      suggesting the possibility of immuno-modulation in treating established
      atherosclerosis. The athero-protective effect of Peptide-2 immunization was
      absent in splenectomized mice but could be conveyed to non-immunized mice via
      adoptive transfer of splenocytes from peptide-2 immunized mice. In conclusion,
      immunization with a specific apo B-100 related peptide sequence reduces aortic
      atherosclerosis and plaque inflammation. Such acquired immunity and athero
      protective effect appears to be mediated by splenocytes. These data demonstrate
      the feasibility of peptide based immunomodulating therapy for atherosclerosis.

PMID- 16288718
TI  - Role of acidic amino acid residues in chitooligosaccharide-binding to
      Streptomyces sp. N174 chitosanase.
AB  - We examined the oligosaccharide binding to Streptomyces sp. N174 chitosanase by
      fluorescence spectroscopy. By means of the tryptophan fluorescence quenching, the
      oligosaccharide binding abilities were evaluated using the three mutant enzymes
      (D57A, E197A, and D201A). The enzymatic activities of the mutant enzymes were
      0.5%, 20.0%, and 38.5% of that of the wild type, respectively. Scatchard plot
      obtained for the wild type enzyme showed a biphasic profile, suggesting that the
      oligosaccharide binds to the chitosanase with two different binding sites (the
      high affinity site and the low affinity site). In contrast, Scatchard plot for
      E197A exhibited a monophasic profile, in which the slope of the line corresponds
      to that for the low affinity binding of the wild type enzyme. A monophasic
      profile was also obtained for D201A, but the slope of the line was similar to
      that of the high affinity binding. Thus, we conclude that Glu197 and Asp201 are
      responsible for oligosaccharide binding at the high affinity site and the low
      affinity site, respectively, which correspond to the (-n) subsites and the (+n)
      subsites (n=1, 2, and 3). The fluorescence quenching was very weak in D57A,
      suggesting a strong contribution of this residue to the oligosaccharide binding.

PMID- 16288719
TI  - Role of IL-27-producing dendritic [corrected] cells in Th1-immunity polarization
      in Lewis rats.
AB  - Lewis and Brown Norway rats are entirely different with respect to the
      polarization of their immune responses (Th1 and Th2, respectively). We found that
      naive Lewis rat splenocytes treated in vitro with heat-killed Mycobacterium
      tuberculosis (Mtb) upregulate the expression of both subunits of IL-27 (IL-27p28
      and EBI3). Mtb treatment caused naive Lewis rat splenocytes to express 4.6-fold
      more IL-27p28 than Mtb-treated Brown Norway rat splenocytes 6h after the
      treatment. Although WSX-1, the IL-27 receptor, was not induced by Mtb treatment
      in splenocytes from either rat strain, Lewis rats expressed significantly higher
      levels of the IL-27 signal transducers T-bet and IL-12Rbeta2 than Brown Norway
      rats. Flow cytometric analysis of dendritic cells from bone marrow cells revealed
      Lewis rats had more IL-27p28-positive cells. Thus, early in the immune response,
      Lewis rats appear to produce higher levels of IL-27 than Brown Norway rats,
      resulting in polarization towards Th1-immunity.

PMID- 16288720
TI  - A protective role of 27-kDa heat shock protein in glucocorticoid-evoked apoptotic
      cell death of hippocampal progenitor cells.
AB  - Hippocampus is one of the most vulnerable tissues to glucocorticoid (GC). In the
      present study, we demonstrate that dexamethasone (DEX), a synthetic GC, induces
      apoptotic cell death in hippocampal progenitor HiB5 cells without any additional
      insult. Interestingly, expression of 27-kDa heat shock protein (HSP27) was
      markedly induced by DEX in time- and dose-dependent manners. This induction was
      dependent on the production of reactive oxygen species (ROS), suggesting that DEX
      evoked oxidative damage to HiB5 cells is responsible for the HSP27 induction. To
      evaluate a possible role of HSP27, we generated two mutant HiB5 cell lines, in
      which expression of HSP27 was inhibited or enhanced by the over-expression of
      HSP27 cDNA with antisense or sense orientation (AS-HSP27 and S-HSP27,
      respectively). DEX-induced apoptotic cell population was significantly increased
      in AS-HSP27 HiB5 cells and evidently decreased in S-HSP27 cells. These results
      indicate that HSP27 protects hippocampal progenitor cells from GC-induced
      apoptotic cell death.

PMID- 16288721
TI  - KDEL-tagged anti-prion intrabodies impair PrP lysosomal degradation and inhibit
      scrapie infectivity.
AB  - Transmissible spongiform encephalopathy or prion diseases are fatal
      neurodegenerative disorders characterized by the conversion of the cellular prion
      protein (PrPC) into the infectious scrapie isoform (PrPSc). We have recently
      demonstrated that anti-prion intrabodies targeted to the lumen of the endoplasmic
      reticulum provide a simple and effective means to inhibit the transport of PrPC
      to the cell surface. Here, we report that they completely block the traffic of
      mature full-length PrPC molecules, impair prion lysosomal degradation, and
      interfere with the early phase of scrapie formation. Since anti-prion intrabodies
      efficiently block PrPSc accumulation in vitro, we investigated whether they could
      also antagonize scrapie infectivity in vivo. We found that mice intracerebrally
      injected with KDEL-8H4-NGF-differentiated PC12 cells infected with scrapie
      neither develop scrapie clinical signs nor brain damage. Furthermore, no protease
      resistant PrPSc is detectable in brains of inoculated animals. These results
      indicate that anti-prion intrabody strategy may be effective against prion
      infection.

PMID- 16288722
TI  - Expression of SRG3, a core component of mouse SWI/SNF chromatin-remodeling
      complex, is regulated by cooperative interactions between Sp1/Sp3 and Ets
      transcription factors.
AB  - SRG3, a mouse homolog of yeast SWI3 and human BAF155, is known to be a core
      component of SWI/SNF chromatin-remodeling complex. We have previously shown that
      SRG3 plays essential roles in early mouse embryogenesis, brain development, and T
      cell development. SRG3 gene expression was differentially regulated depending on
      the developmental stages and exhibited tissue-specific pattern. In this study, we
      showed that the functional interactions between Sp and Ets family transcription
      factors are crucial for the SRG3 expression. Sp1 and Sp3 specifically bound to
      the two canonical Sp-binding sites (GC boxes) at -152 and -114, and a non
      canonical Sp-binding site (CCTCCT motif) at -108 in the SRG3 promoter. Using
      Drosophila SL2 cells, we found that various Sp or Ets family members activate the
      SRG3 promoter through these Sp- or Ets-binding sites, respectively, in a dose
      dependent manner. Intriguingly, different combinatorial expression of Ets and Sp
      factors in SL2 cells resulted in either strong synergistic activation or
      repression of the SRG3 promoter activity. Moreover, the Sp-mediated activation of
      SRG3 promoter required the intact Ets-binding element. Taken together, these
      results suggest that diverse interactions between Sp1/Sp3 and Ets factors are
      crucial for the SRG3 gene expression.

PMID- 16288723
TI  - DNA binding properties of 9-substituted harmine derivatives.
AB  - The beta-carboline alkaloids have been characterized as a group of potential
      antitumor agents. The underlying mechanisms of harmine and its derivatives were
      investigated by DNA binding assay and Topoisomerase (Topo) inhibition assay.
      Meanwhile, the DNA photocleavage potential of these compounds and their
      cytotoxicity were also examined by DNA photocleavage assay and cytotoxicity assay
      in vitro. Harmine and its derivatives exhibited remarkable DNA intercalation
      capacity and significant Topo I inhibition activity but no effect with Topo II.
      Introducing an appropriate substituent into position-9 of beta-carboline nucleus
      enhanced the affinity of the drug to DNA resulting in remarkable Topo I
      inhibition effects. These results suggested that the ability of these compounds
      to act as intercalating agents and Topo I inhibitors was related to the antitumor
      activity. Moreover, these data showing a correlation between cytotoxicity and
      Topo I inhibition or DNA binding capacity are very important as they strongly
      suggested that the Topo I-mediated DNA cleavage assay and DNA binding assay could
      be used as a guide to design and develop superior analogues for antitumor
      activities.

PMID- 16288724
TI  - Effect on stability, degradation, expression, and targeting of aquaporin-2 water
      channel by hyperosmolality in renal epithelial cells.
AB  - To investigate the stability, degradation, expression, and targeting of aquaporin
      2 (AQP2) by hyperosmolality, stably transfected mIMCD-3 cells expressing AQP2
      (AQP2/IMCD3) were generated. In AQP2/IMCD3 cells, both nonglycosylated (ng-AQP2)
      and glycosylated (g-AQP2) forms were detected by immunoblot. The stability of ng
      AQP2 decreased with the lapse of time, whereas that of g-AQP2 was stable. NaCl,
      but not urea, destabilized ng-AQP2. The half-life of ng-AQP2 in isotonic
      conditions was approximately 5 h, whereas that in medium supplemented with NaCl
      was approximately 1.5 h. Urea enhanced it compared to isotonic conditions. These
      findings indicate that the stability of ng-AQP2 is enhanced by urea, but not
      NaCl. The degradation of ng-AQP2 was dependent on proteasome and lysosome
      degradation pathways. The expression of ng-AQP2 was increased by hyperosmolality.
      Cell surface biotinylation experiments revealed that hyperosmolality enhanced the
      apical membrane insertion of ng-AQP2. These results indicate that hyperosmolality
      plays an important role in the stability, degradation, expression, and targeting
      of ng-AQP2.

PMID- 16288725
TI  - Characterization of two small cryptic plasmids from Pseudomonas sp. strain S-47.
AB  - Two small cryptic plasmids, p47L and p47S, identified in Pseudomonas sp. S-47
      were characterized by determination of DNA sequences and physical and functional
      maps. They are 3084 and 1782 bp in length, respectively, with GC contents of
      63.55 and 65.21%. The detection of single-strand DNAs of both plasmids indicates
      that they replicate by a rolling-circle mechanism. The deduced polypeptide
      encoded by the rep gene of p47L is homologous with Rep proteins of plasmids
      belonging to the pIJ101/pJV1 family, which are known to replicate by the rolling
      circle mechanism. Despite containing a homologous signature with Rep proteins of
      rolling-circle replicating (RCR) plasmids in the pT181 family, the Rep of p47S
      lacks significant homology with Rep proteins of this family and is missing a
      region similar to the family's replication origin (dso). Based on the rep
      sequence comparisons, p47L falls into a previously defined plasmid family whereas
      p47S defines a new family of RCR plasmid.

PMID- 16288726
TI  - ApRab11, a cnidarian homologue of the recycling regulatory protein Rab11, is
      involved in the establishment and maintenance of the Aiptasia-Symbiodinium
      endosymbiosis.
AB  - Endosymbiotic association of the Symbiodinium dinoflagellates (zooxanthellae)
      with their cnidarian host cells involves an alteration in the development of the
      alga-enclosing phagosomes. To uncover its molecular basis, we previously
      investigated and established that the intracellular persistence of the
      zooxanthella-containing phagosomes involves specific alga-mediated interference
      with the expression of ApRab5 and ApRab7, two key endocytic regulatory Rab
      proteins, which results in the selective retention of the former on and exclusion
      of the later from the organelles. Here we examined the role of ApRab11, a
      cnidarian homologue of the key endocytic recycling regulator, Rab11, in the
      Aiptasia-Symbiodinium endosymbiosis. ApRab11 protein shared 88% overall sequence
      identity with human Rab11A and contained all Rab-specific signature motifs. Co
      localization and mutagenesis studies showed that EGFP-tagged ApRab11 was
      predominantly associated with recycling endosomes and functioned in the recycling
      of internalized transferrin. In phagocytosis of latex beads, ApRab11 was quickly
      recruited to and later gradually removed from the developing phagosomes.
      Significantly, although ApRab11 immunoreactivity was rapidly detected on the
      phagosomes containing either newly internalized, heat-killed zooxanthellae, or
      resident zooxanthellae briefly treated with the photosynthesis inhibitor DCMU, it
      was rarely observed in the majority of phagosomes containing either newly
      internalized live, or healthy resident, zooxanthellae. It was concluded that
      through active exclusion of ApRab11 from the phagosomes in which they reside,
      zooxanthellae interfere with the normal recycling process required for efficient
      phagosome maturation, and thereby, secure their intracellular persistence, and
      consequently their endosymbiotic relationship with their cnidarian hosts.

PMID- 16288727
TI  - Cell-mediated LDL oxidation: the impact of transition metals and transferrin.
AB  - Activated monocytes release oxygen radicals by respiratory burst and oxidative
      damage can be accelerated by transition metals. We investigated the cell-mediated
      and metal-catalysed in vitro oxidation of low-density lipoproteins (LDL), as well
      as the impact of the metal-binding protein transferrin (Tf). LDL oxidation was
      measured by monitoring the increase in fluorescence (350/440 nm
      excitation/emission). Maximal respiratory burst by U937 cells was achieved after
      96 h differentiation with retinoic acid and dihydroxyvitamin D3 followed by
      stimulation with opsonised zymosan. Addition of activated cells resulted in the
      LDL oxidation, even in the absence of transition metals. Moreover, activated
      cells greatly enhanced metal-catalysed oxidative modifications, especially in the
      presence of copper. By binding metals, Tf was able to strongly impair this
      process. In conclusion, by generating oxygen radicals, activated U937 cells were
      able to oxidise LDL. The oxidising process was most pronounced in the presence of
      copper and could be blocked by Tf.

PMID- 16288728
TI  - Differential effects of TGF-beta1 on telomerase activity in thyroid carcinoma
      cell lines.
AB  - The aim of the present study was to investigate the effect of transforming growth
      factor-beta1 (TGF-beta1) on telomerase activity in a panel of human anaplastic
      thyroid carcinoma (ATC) cell lines. Addition of TGF-beta1 decreased the
      telomerase activity in HTh 74 and KTC-1 cells, while in C 643 and HTh 7 an
      increased activity was observed. The decreased telomerase activity appeared to be
      due to transcriptional repression of the hTERT promoter. Addition of a PI-3
      kinase inhibitor (LY294002) abrogated the stimulatory effect of TGF-beta1 on the
      telomerase activity, indicating the possible involvement of hTERT activation via
      phosphorylation. Furthermore, the MEK-inhibitor U0126 had similar effects
      suggesting dual regulatory mechanisms. Interestingly, the cell lines differed
      genetically in that ATC cell lines responding with increased telomerase activity
      harbored a p53 mutation. In conclusion, TGF-beta1 exerts opposing effects on
      telomerase activity in ATC cell lines, possibly reflecting deregulation of TGF
      beta1 signaling in a more malignant genotype.

PMID- 16288729
TI  - Effects of peripheral inflammation on activation of ERK in the rostral
      ventromedial medulla.
AB  - In the present study, the activation of extracellular signal-regulated kinase
      (ERK) in the rostral ventromedial medulla (RVM) following the injection of
      complete Freund's adjuvant (CFA) into the rat hindpaw was examined in order to
      clarify the mechanisms underlying the dynamic changes in the descending pain
      modulatory system after peripheral inflammation. Phospho-extracellular signal
      regulated kinase-immunoreactive (p-ERK-IR) neurons were observed in the nucleus
      raphe magnus (NRM) and nucleus reticularis gigantocellularis pars alpha (GiA).
      Inflammation induced the activation of ERK in the RVM, with a peak at 7 h after
      the injection of CFA into the hindpaw and a duration of 24 h. In the RVM, the
      number of p-ERK-IR neurons per section in rats killed at 7 h after CFA injection
      (14.2 +/- 1.7) was significantly higher than that in the control group (4.5 +/-
      0.9) [P < 0.01]. At 7 h after CFA injection, about 60% of p-ERK-IR neurons in the
      RVM were serotonergic neurons. The percentage of RVM serotonergic neurons that
      are also p-ERK positive in the rats with inflammation (20.5% +/- 2.3%) was seven
      times higher than that in control rats (2.7% +/- 1.4%) [P < 0.01]. These findings
      suggest that inflammation-induced activation of ERK in the RVM may be involved in
      the plasticity in the descending pain modulatory system following inflammation.

PMID- 16288730
TI  - Mechanisms of regulation of G protein-coupled receptor kinases (GRKs) and
      cardiovascular disease.
AB  - The G protein-coupled receptor kinases (GRKs) participate with arrestins in the
      regulation and signal propagation of multiple G protein-coupled receptors (GPCR)
      of key physiological and pharmacological relevance in the cardiovascular system.
      The complex mechanisms of regulation of GRK expression, degradation and function
      are being unveiled gradually. The levels of these kinases are known to change in
      pathological situations such as heart failure, hypertrophy and hypertension, and
      in animal models of these diseases. A better understanding of the mechanisms
      underlying these changes and of how these alterations participate in the
      triggering or progression of cardiovascular disease may contribute to the design
      of novel diagnostic and therapeutic strategies.

PMID- 16288732
TI  - Specific phonological impairments in dyslexia revealed by eyetracking.
AB  - Phonological deficits in dyslexia are typically assessed using metalinguistic
      tasks vulnerable to extraneous factors such as attention and memory. The present
      work takes the novel approach of measuring phonology using eyetracking. Eye
      movements of dyslexic children were monitored during an auditory word recognition
      task in which target items in a display (e.g., candle) were accompanied by
      distractors sharing a cohort (candy) or rhyme (sandal). Like controls, dyslexics
      showed slower recognition times when a cohort distractor was present than in a
      baseline condition with only phonologically unrelated distractors. However,
      unlike controls, dyslexic children did not show slowed recognition of targets
      with a rhyme distractor, suggesting they had not encoded rhyme relationships.
      This was further explored in an overt phonological awareness test of cohort and
      rhyme. Surprisingly, dyslexics showed normal rhyme performance but poorer
      judgment of initial sounds on these overt tests. The results implicate impaired
      knowledge of rhyme information in dyslexia; however they also indicate that
      testing methodology plays a critical role in how such problems are identified.

PMID- 16288731
TI  - Induction and localization of NOD2 protein in human endothelial cells.
AB  - NOD2 is mainly expressed in human monocytes/macrophages and intestinal epithelial
      cells and has been speculated to play in gut physiology. However, whether NOD2 is
      expressed in vascular endothelium is not currently determined. Human umbilical
      vascular endothelial cells (HUVECs) minimally expressed NOD2 gene, whereas
      stimulation of HUVEC with bacterial LPS, IL-1beta, or TNF-alpha resulted in
      significant up-regulation of NOD2. NOD2 protein was mostly localized in the
      cytoplasm. Overexpression of wild-type NOD2 (WT-NOD2) gene induced NF-kappaB
      dependent transcriptional activity and this activity was further increased by
      muramyl dipeptide (MDP). Otherwise, down-regulation of WT-NOD2 gene by antisense
      NOD2 abolished NF-kappaB-dependent transcriptional activity mediated by either WT
      NOD2 itself or MDP. Since vascular endothelial cells, like macrophages and
      epithelial cells, are critical targets for the circulating bacterial molecules
      such as MDP, collectively, the results presented here suggest that NOD2 may play
      an important role in recognizing structural patterns of bacterial pathogen in the
      endothelium.

PMID- 16288733
TI  - What is the relationship between synaesthesia and visuo-spatial number forms?
AB  - This study compares the tendency for numerals to elicit spontaneous perceptions
      of colour or taste (synaesthesia) with the tendency to visualise numbers as
      occupying particular visuo-spatial configurations (number forms). The prevalence
      of number forms was found to be significantly higher in synaesthetes experiencing
      colour compared both to synaesthetes experiencing taste and to control
      participants lacking any synaesthetic experience. This suggests that the presence
      of synaesthetic colour sensations enhances the tendency to explicitly represent
      numbers in a visuo-spatial format although the two symptoms may nevertheless be
      logically independent (i.e. it is possible to have number forms without colour,
      and coloured numbers without forms). Number forms are equally common in men and
      women, unlike previous reports of synaesthesia that have suggested a strong
      female bias. Individuals who possess a number form are also likely to possess
      visuo-spatial forms for other ordinal sequences (e.g. days, months, letters)
      which suggests that it is the ordinal nature of numbers rather than numerical
      quantity that gives rise to this particular mode of representation. Finally, we
      also describe some consequences of number forms for performance in a number
      comparison task.

PMID- 16288734
TI  - Representational and executive selection resources in 'theory of mind': evidence
      from compromised belief-desire reasoning in old age.
AB  - Effective belief-desire reasoning requires both specialized representational
      capacities-the capacity to represent the mental states as such-as well as
      executive selection processes for accurate performance on tasks requiring the
      prediction and explanation of the actions of social agents. Compromised belief
      desire reasoning in a given population may reflect failures in either or both of
      these systems. We report evidence supporting this two-process model from belief
      desire reasoning tasks conducted with younger and older adult populations. When
      task inferential complexity is held constant, neither group showed specific
      difficulty with reasoning about mental state content as compared with non-mental
      state content. However, manipulations that systematically increase executive
      performance demands within belief-desire reasoning caused systematic decreases in
      task performance in both older and younger adult groups. Moreover, the effect of
      increasing executive demands was disproportionately greater in the older group.
      Regression analysis indicated that measures of processing speed and inhibition
      contributed most to explaining variance in accuracy and response times in the
      belief-desire reasoning tasks. These results are consistent with the idea that
      compromised belief-desire reasoning in old age is likely the result of age
      related decline in executive selection skills that supplement core mental state
      representational abilities, rather than as a result of failures in the
      representational system itself.

PMID- 16288735
TI  - Stage-specific induction of DNA methyltransferases in olfactory receptor neuron
      development.
AB  - DNA methylation-dependent gene silencing, mediated by DNA methyltransferases
      (DNMTs), is essential for normal mammalian development and its dysregulation has
      been implicated in neurodevelopmental disorders. Despite this, little is known
      about DNMTs in the developing or mature nervous system. Here, we show that DNMT1,
      3a and 3b are expressed at discrete developmental stages in the olfactory neuron
      lineage, coincident with key shifts in developmental gene expression. DNMT1 is
      induced in cycling progenitors and is retained in post-mitotic olfactory receptor
      neurons (ORNs). DNMT3b is restricted to mitotic olfactory progenitors, whereas
      DNMT3a is expressed only in post-mitotic immature neurons prior to ORN terminal
      maturation, coincident with histone deacetylase 2 (HDAC2), a key downstream
      effector of methylation-dependent chromatin condensation. Similar stage-specific
      expression of DNMT3b and 3a was also found in other developing sensory and CNS
      neurons. This suggests that progressive lineage restriction regulated by
      methylation-dependent silencing could be a highly conserved mechanism shared by
      multiple lineages in the developing nervous system.

PMID- 16288736
TI  - Alcohol dependence and gene x environment interaction in emotion regulation: Is
      serotonin the link?
AB  - Alcohol dependence is characterized by frequent, compulsive and uncontrolled
      consumption of alcohol associated with behavior of maladaption and destruction.
      It is an etiologically and clinically heterogeneous syndrome, moderately to
      highly heritable, and caused by interaction of genes and environment. Alcohol
      dependence is related to other psychiatric diseases by common neurobiological
      pathways, including those that modulate reward, behavioral control as well as
      anxiety and stress response. Alcohol induces adaptive changes in brain function
      providing the basis for tolerance, craving, withdrawal, and emotional
      disturbance. The differentiation of psychobiological traits of addictive behavior
      reflecting neurobiological processes is therefore of particular importance for
      the dissection of the complex genetic susceptibility to alcohol dependence. A
      central serotonin (5-HT) deficit is thought to be involved in the pathogenesis of
      alcohol dependence by modulating motivational behavior, neuroadaptive processes,
      and resulting emotional disturbance. 5-HT-related impulsive, aggressive, and
      suicidal behavior has been linked to a primordial personality that is susceptible
      to alcohol dependence. Although variations in many of the genes that encode
      receptors, enzymes, and transporters of the 5-HT system have been tested as risk
      factors for alcohol dependence, genetic analyses of 5-HT signaling in alcohol
      dependence have mainly been focused on the 5-HT transporter (5-HTT) gene. Due to
      its central role in the fine-tuning serotonergic neurotransmission, a regulatory
      variant of the 5-HTT, which is associated with anxiety related traits, is not
      only a key player in the neurobiological mechanism of gene x environment
      interaction in the etiology of depression, but also contributes to the risk to
      develop alcohol dependence with antisocial behavior and suicidality. Evidence for
      a modulatory effect of allelic variation of 5-HTT function on limbic circuit
      responses to emotional stimuli suggests that genotype-endophenotype correlations
      may be accessible to molecular functional imaging of the brain. These new
      developments have broad implications for our understanding how genetic
      vulnerability to alcohol dependence is manifested in the brain's response to
      emotional stimuli.

PMID- 16288737
TI  - Neuropsychopharmacology of drug seeking: Insights from studies with second-order
      schedules of drug reinforcement.
AB  - Second-order schedules of reinforcement model complex chains of responding for
      rewards such as food or drugs. Derived from studies of conditioned reinforcement,
      an important feature of these schedules is that responding is maintained by the
      response-dependent presentation of conditioned stimuli. They are thus well-suited
      to the study of the influences over drug seeking exerted by drug-associated
      stimuli. In the present review, we summarise studies investigating the
      neurobiology and neuropsychopharmacology of responding for cocaine under a second
      order schedule of reinforcement. We conclude that limbic-striatal circuitries
      underlie drug seeking measured in this way. Emphasis is placed on potential
      interactions between structures within these subsystems by reviewing
      neuropsychopharmacological studies in which antagonists selective for either
      glutamate or dopamine receptors have been infused directly into limbic, cortical
      and striatal areas.

PMID- 16288738
TI  - Enhancement of transdermal fentanyl and buprenorphine antinociception by
      transdermal delta9-tetrahydrocannabinol.
AB  - Previous studies have demonstrated that delta9-tetrahydrocannabinol (THC)
      enhances the antinociceptive potency of many opioids administered by a variety of
      different routes of administration. We hypothesized that THC would enhance
      fentanyl or buprenorphine analgesia via the transdermal route of administration.
      THC was first demonstrated to enhance opioid antinociception when both drugs were
      administered parenterally in a hairless guinea pig model using the pin prick
      test. A low dose of THC (50 mg/kg, i.p.) produced no antinociception. However,
      THC enhanced the potency of s.c. fentanyl by 6.7-fold, and s.c. buprenorphine in
      a non-parallel fashion. For the transdermal studies, THC, fentanyl or
      buprenorphine was applied by pipette to the skin of the dorsum between the fore-
      and hind-flanks and covered with individual Tegederm patches. THC (400 mg/kg)
      produced no antinociception. However, THC enhanced fentanyl's potency by 3.7-fold
      at 2-h, and 5.8-fold at 4-h. Buprenophine's potency was increased 8.2-fold at 2-h
      and 7.2-fold at 4-h when co-administered with THC. These results indicate that
      the enhancement of transdermal opioids by THC could lead to the design of an
      effective combination analgesic patch.

PMID- 16288739
TI  - Characterization of a serine protease-mediated cell death program activated in
      human leukemia cells.
AB  - Tightly controlled proteolysis is a defining feature of apoptosis and caspases
      are critical in this regard. Significant roles for non-caspase proteases in cell
      death have been highlighted. Staurosporine causes a rapid induction of apoptosis
      in virtually all mammalian cell types. Numerous studies demonstrate that
      staurosporine can activate cell death under caspase-inhibiting circumstances. The
      aim of this study was to investigate the proteolytic mechanisms responsible for
      cell death under these conditions. To that end, we show that inhibitors of serine
      proteases can delay cell death in one such system. Furthermore, through profiling
      of proteolytic activation, we demonstrate, for the first time, that staurosporine
      activates a chymotrypsin-like serine protease-dependent cell death in HL-60 cells
      independently, but in parallel with the caspase controlled systems. Features of
      the serine protease-mediated system include cell shrinkage and apoptotic
      morphology, regulation of caspase-3, altered nuclear morphology, generation of an
      endonuclease and DNA degradation. We also demonstrate a staurosporine-induced
      activation of a putative 16 kDa chymotrypsin-like protein during apoptosis.

PMID- 16288740
TI  - The PCNA-associated factor KIAA0101/p15(PAF) binds the potential tumor suppressor
      product p33ING1b.
AB  - The KIAA0101/p15(PAF)/OEATC-1 protein was initially isolated in a yeast two
      hybrid screen for proliferating cell nuclear antigen (PCNA) binding partners, and
      was shown to bind PCNA competitively with the cell cycle regulator p21(WAF). PCNA
      is involved in DNA replication and damage repair. Using polyclonal antisera
      raised against a p15(PAF) fusion protein, we have shown that in a range of
      mammalian tumor and non-tumor cell lines the endogenous p15(PAF) protein
      localises to the nucleus and the mitochondria. Under normal conditions no co
      localisation with PCNA could be detected, however following exposure to UV it was
      possible to co-immunoprecipitate p15(PAF) and PCNA from a number of cell lines,
      suggesting a UV-enhanced association of the two proteins. Overexpression of
      p15(PAF) in mammalian cells was also found to protect cells from UV-induced cell
      death. Based on similarities between the behaviour of p15(PAF) and the potential
      tumor suppressor product p33ING1b, we have further shown that these two proteins
      interact in the same complex in cell cultures. This suggests that p15(PAF) forms
      part of a larger protein complex potentially involved in the regulation of DNA
      repair, apoptosis and cell cycle progression.

PMID- 16288741
TI  - Trypanosoma cruzi: effects of infection on cathepsin D activity in the midgut of
      Rhodnius prolixus.
AB  - Cathepsin D activity was estimated in midgut homogenates from Rhodnius prolixus,
      uninfected and experimentally infected with Trypanosoma cruzi, at different times
      after blood ingestion. No enzyme activity was found in the anterior midgut and
      rectum. In the posterior midgut, enzyme activity was found both in lumen and
      wall. In starved uninfected insects, in lumen and wall, cathepsin D activity was
      high, decreasing to a constant rate at 1-15 days after feeding. In insects
      infected with T. cruzi cathepsin D activity increased 1 and 3 days after blood
      meal. We suggest that these changes in cathepsin D activity in R. prolixus
      posterior midgut are due to the establishment of T. cruzi infection.

PMID- 16288742
TI  - An ABC transporter mediating the membrane detachment of bacterial lipoproteins
      depending on their sorting signals.
AB  - Bacterial lipoproteins are anchored to membranes through a lipid moiety attached
      to the N-terminal Cys. Escherichia coli possesses more than 90 species of
      lipoproteins, most of which are localized in the outer membrane and others in the
      inner membrane. Sorting of lipoproteins to the outer membrane requires the Lol
      system comprising five Lol proteins. An ATP-binding cassette transporter, LolCDE,
      initiates the lipoprotein sorting by mediating the detachment of outer membrane
      specific lipoproteins from the inner membrane. LolCDE does not recognize
      lipoproteins possessing Asp at position 2, which therefore remain anchored to the
      inner membrane. We will discuss the mechanism of LolCDE based on data obtained
      through in vitro experiments.

PMID- 16288743
TI  - Topo II alpha reporter mice reveal proliferative regions in the epidermis and
      small intestine.
AB  - We investigated topoisomerase II alpha promoter activity in epithelia. In
      confluent human keratinocytes the promoter (-557 to+90 bp) was upregulated by
      oncogenic Ras. In transgenic mice expressing GFP via the promoter, GFP expression
      in undamaged epidermis was confined to growing hair follicles. GFP was also
      expressed in intestinal crypts. GFP expression was upregulated in epidermis
      following wounding or phorbol ester treatment. In each situation GFP expression
      correlated with high endogenous topoisomerase II alpha expression and high
      proliferation. The mice therefore provide a useful model for non-invasive imaging
      of regions of high proliferation in normal or damaged epidermis.

PMID- 16288744
TI  - 2-Arachidonoylglycerol, an endogenous cannabinoid receptor ligand, enhances the
      adhesion of HL-60 cells differentiated into macrophage-like cells and human
      peripheral blood monocytes.
AB  - 2-Arachidonoylglycerol (2-AG), an endogenous cannabionoid receptor (CB1 and CB2)
      ligand, enhanced the adhesion of HL-60 cells differentiated into macrophage-like
      cells to fibronectin and the vascular cell adhesion molecule-1. The CB2 receptor,
      Gi/Go, intracellular free Ca(2+) and phosphatidylinositol 3-kinase were shown to
      be involved in 2-AG-induced augmented cell adhesion. 2-AG also enhanced the
      adhesion of human monocytic leukemia U937 cells and peripheral blood monocytes.
      These results strongly suggest that 2-AG plays some essential role in
      inflammatory reactions and immune responses by inducing robust adhesion to
      extracellular matrix proteins and adhesion molecules in several types of
      inflammatory cells and immune-competent cells.

PMID- 16288745
TI  - Ha-Ras sensitizes transformed mouse skin cells to Anisomycin-induced apoptosis.
AB  - Efforts have been made to develop a chemoprevention that selectively triggers
      apoptosis in malignant cancer cells. Here, we demonstrated that a mutated Ha-Ras
      activity is required in Anisomycin-induced apoptosis in transformed
      keratinocytes. Anisomycin stimulates JNK activity and apoptosis in oncogenic Ha
      Ras positive cells, but not in normal keratinocytes. This effect was demonstrated
      in stably transfected cells with dominant negative Ha-Ras, that protected
      transformed cells, and oncogenic Ha-Ras that sensitized non-transformed cells to
      Anisomycin-induced apoptosis. Lastly, the treatment of cells with inhibitors of
      the JNK displayed resistance to Anisomycin induced apoptosis. These data suggests
      that the oncogenic Ha-Ras is important for Anisomycin-induced JNK activation and
      apoptosis in transformed keratinocytes.

PMID- 16288746
TI  - Platelet-activating factor induces matrix metalloproteinase-9 expression through
      Ca(2+)- or PI3K-dependent signaling pathway in a human vascular endothelial cell
      line.
AB  - Platelet-activating factor (PAF) augments angiogenesis by promoting the synthesis
      of a variety of angiogenic factors, via the nuclear factor (NF)-kappaB
      activation. Recently, we reported that PAF upregulates MMP-9 expression in a NF
      kappaB-dependent manner. In this study, we investigated the signaling pathway
      involved in PAF-induced MMP-9 expression in ECV304 cells. Our current data
      indicate that the Ca(2+)- or phosphatidylinositol 3-kinase (PI3K)-dependent
      signaling pathway is necessary for PAF-induced MMP-9 expression. Furthermore, PAF
      induced NF-kappaB activation was blocked by selective inhibitors of Ca(2+), PI3K,
      or extracellular signal-regulated kinase (ERK). Our results suggest that PAF
      induced MMP-9 expression, in a NF-kappaB-dependent manner, is regulated by
      Ca(2+), PI3K and ERK signaling pathways.

PMID- 16288747
TI  - A major ozonation product of cholesterol, 3beta-hydroxy-5-oxo-5,6-secocholestan-6
      al, induces apoptosis in H9c2 cardiomyoblasts.
AB  - Cholesterol, a major neutral lipid component of biological membranes and the lung
      epithelial lining fluids, is susceptible to oxidation by reactive oxygen and
      nitrogen species including ozone. The oxidation by ozone in biological
      environments results in the formation of 3beta-hydroxy-5-oxo-5,6-secocholestan-6
      al (cholesterol secoaldehyde or CSeco, major product) along with some other minor
      products. Recently, CSeco has been implicated in the pathogenesis of
      atherosclerosis and Alzheimer's disease. In this communication, we report that
      CSeco induces cytotoxicity in H9c2 cardiomyoblasts with an IC(50) of 8.9+/-1.29
      microM (n=6). The observed effect of CSeco at low micromolar concentrations
      retained several key features of apoptosis, such as changes in nuclear
      morphology, phosphatidylserine externalization, DNA fragmentation, and caspase
      3/7 activity. Treatment of cardiomyocytes with 5 microM CSeco for 24h, for
      instance, resulted in 30.8+/-3.28% apoptotic and 1.8+/-1.11% of necrotic cells as
      against DMSO controls that only showed 1.3+/-0.33% of apoptosis and 1.6+/-0.67%
      of necrosis. In general, the loss of cellular viability paralleled the increased
      occurrence of apoptotic cells in various CSeco treatments. This study, for the
      first time, demonstrates the induction of apoptotic cell death in cardiomyocytes
      by a cholesterol ozonation product, implying a role for ozone in myocardial
      injury.

PMID- 16288748
TI  - Interaction between HIF-1 alpha (ODD) and hARD1 does not induce acetylation and
      destabilization of HIF-1 alpha.
AB  - Hypoxia inducible factor-1 alpha (HIF-1 alpha) is a central component of the
      cellular responses to hypoxia. Hypoxic conditions result in stabilization of HIF
      1 alpha and formation of the transcriptionally active HIF-1 complex. It was
      suggested that mammalian ARD1 acetylates HIF-1 alpha and thereby enhances HIF-1
      alpha ubiquitination and degradation. Furthermore, ARD1 was proposed to be down
      regulated in hypoxia thus facilitating the stabilization of HIF-1 alpha. Here we
      demonstrate that the level of human ARD1 (hARD1) protein is not decreased in
      hypoxia. Moreover, hARD1 does not acetylate and destabilize HIF-1 alpha. However,
      we find that hARD1 specifically binds HIF-1 alpha, suggesting a putative, still
      unclear, connection between these proteins.

PMID- 16288749
TI  - Proinflammatory adipocytokines induce TIMP-1 expression in 3T3-L1 adipocytes.
AB  - Tissue inhibitor of metalloproteinase (TIMP)-1 is an adipocyte-secreted protein
      upregulated in obesity which promotes adipose tissue development. Furthermore,
      the proinflammatory adipocytokines tumor necrosis factor alpha (TNFalpha) and
      interleukin (IL)-6 induce insulin resistance, and plasma concentrations are
      increased during weight gain. In the current study, the impact of TNFalpha and IL
      6 on TIMP-1 mRNA and protein expression was determined in 3T3-L1 adipocytes.
      Interestingly, TNFalpha and IL-6 induced TIMP-1 protein secretion more than 3-
      and 2-fold, respectively. Furthermore, TIMP-1 mRNA was upregulated in a time- and
      dose-dependent fashion. Inhibitor experiments suggested that nuclear factor
      kappaB and p 44/42 mitogen-activated protein kinase are involved in both, basal
      and adipocytokine-induced TIMP-1 expression. Moreover, the thiazolidinedione
      troglitazone partly reversed TNFalpha- but not IL-6-induced TIMP-1 synthesis.
      Taken together, we demonstrate that TIMP-1 expression is selectively upregulated
      in fat cells by proinflammatory adipocytokines and might play a role in
      maintaining adipose tissue mass in obesity.

PMID- 16288750
TI  - High cholesterol diet induces tau hyperphosphorylation in apolipoprotein E
      deficient mice.
AB  - We analysed the effects of high cholesterol (HC) intake and reduced
      apolipoprotein E (apoE) activity on tau phosphorylation and on the activities of
      the major tau kinases and phosphatases in brains from wild-type and apoE-knockout
      (apoEKO) mice. We show that HC diet potently induced intraneuronal accumulation
      of hyperphosphorylated tau in apoEKO mice, as well as upregulation of several tau
      kinases, without affecting tau phosphatases. Our results suggest an interaction
      between dietary and genetic factors in the development of tauopathies, which can
      be relevant in humans, where the apoE4 isoform could have a lack of function as
      compared to other isoforms.

PMID- 16288751
TI  - Apical cell adhesion molecule, trophinin, localizes to the nuclear envelope.
AB  - Trophinin mediates homophilic and apical cell adhesion between trophoblastic
      cells and endometrial epithelial cells, which is potentially the initial
      attachment step in human embryo implantation. Since trophinin is an atypical
      membrane protein without the signal sequence, it is possible that trophinin
      localizes to the cytoplasm. By treating trophinin-expressing trophoblastic cells
      with a series of detergents, we found significant levels of endogenous trophinin
      in the cytoplasm, particularly at the nuclear envelope (NE). Fluorescence
      photobleaching of GFP-trophinin expressed in COS-1 cells showed the stable
      association of trophinin with the NE, suggesting an additional role of trophinin
      besides apical cell adhesion.

PMID- 16288752
TI  - Current challenges in quantitative modeling of epidermal growth factor signaling.
AB  - Over the last decade, epidermal growth factor (EGF) signaling has been used
      repeatedly as a test-bed for pioneering computational systems biology. Recent
      breakthroughs in our molecular understanding of EGF signaling pose new challenges
      for mathematical modeling strategies. Three key areas emerge as particularly
      relevant: the pervasive importance of compartmentalization and endosomal
      trafficking; the complexity of signalosome complexes; and the regulatory
      influence of diffusion and spatiality. Each one of them demands a drastic change
      in current computational approaches. We discuss recent developments in the field
      that address these emerging aspects in a new generation of more realistic - and
      potential more useful - models of EGF signaling.

PMID- 16288753
TI  - Regulation of the avian kidney by arginine vasotocin.
AB  - Nonapeptides secreted by the neurohypophysis have important roles in vertebrate
      cardio-fluid homeostasis. In birds, those peptides include mesotocin (the
      representative of the neutral, or oxytocin-like, nonapeptide family) and
      vasotocin (the representative of the basic, or vasopressin-like, hormones). The
      function of mesotocin is not well defined, but it does appear to have
      osmoregulatory functions. Vasotocin is considered the primary avian antidiuretic
      hormone. Receptors for AVT in avian kidney-either on renal vasculature or on the
      tubules-have yet to be localized or identified. However, AVT quite certainly
      effects antidiuresis via both vascular and tubular mechanisms. The former entail
      a reduction in the rate of glomerular filtration, apparently via constriction of
      afferent arterioles. Evidence for the latter (direct tubular action of AVT) has
      accumulated in recent years and includes enhanced fractional tubular water
      reabsorption, activation of second messenger (cAMP) in thick ascending limbs and
      collecting ducts, and modest AVT-stimulated water permeability in collecting
      ducts associated with expression of aquaporins. The relative importance of the
      renal vascular vs. tubular actions in birds likely depend on the dose of the
      hormone, the physiological condition of the animal, and the species of bird.

PMID- 16288754
TI  - Distribution of somatostatin immunoreactivity in the brain of the snake Bothrops
      jararaca.
AB  - The distribution of perikarya and fibers containing somatostatin was studied in
      the brain of the snake Bothrops jararaca by means of immunohistochemistry using
      an antiserum against synthetic somatostatin. Immunoreactive perikarya and fibers
      were localized in telencephalic, diencephalic and mesencephalic areas. In the
      telencephalon, numerous immunoreactive perikarya were found in the medial,
      dorsomedial, dorsal and lateral cortex, mainly in the deep plexiform layer, less
      so in the cellular layer, but not in the superficial plexiform layer.
      Immunoreactive perikarya were also observed in the dorsal ventricular ridge, the
      nucleus of the diagonal band of Broca, amygdaloid complex, septum and lamina
      terminalis. In the diencephalon, labelled cells were observed in the
      paraventricular, periventricular hypothalamic and in the recessus infundibular
      nuclei. In the mesencephalon, immunoreactive perikarya were seen in the
      mesencephalic reticular formation, reticular nucleus of the isthmus and torus
      semicircularis. Labelled fibers ran along the diencephalic floor and the inner
      zone of the median eminence, and ended in the neural lobe of the hypophysis.
      Other fibers were observed in the outer zone of the median eminence close to the
      portal vessels and in the septum, lamina terminalis, retrochiasmatic nucleus,
      deep layers of the tectum, periventricular gray and granular layer of the
      cerebellum. Our data suggest that somatostatin may function as a mediator of
      adenohypophysial secretion as well as neurotransmitter and/or neuromodulator
      which can regulate the neurohypophysial peptides in the snake B. jararaca.

PMID- 16288755
TI  - Hormonal control of salt and water balance in vertebrates--a symposium.

PMID- 16288756
TI  - Genomic structure of the sea lamprey growth hormone-encoding gene.
AB  - Growth hormone (GH) belongs to a family of pituitary hormones together with
      prolactin and somatolactin. In our previous study, GH and its cDNA were
      identified in the pituitary gland of the sea lamprey, Petromyzon marinus, an
      extant representative of the most ancient class of vertebrates, and isolated GH
      stimulated expression of insulin-like growth factor in the liver. The evidence
      suggests that GH is the ancestral hormone in the molecular evolution of the
      GH/PRL/SL family and that the endocrine mechanism for growth stimulation was
      established at an early stage in the evolution of vertebrates. To further
      understand the molecular evolution of the GH/PRL/SL gene family, we report the
      genomic structure of sea lamprey GH including its 5'-flanking region, being
      cloned by PCR using specific primers prepared from its cDNA. The sea lamprey GH
      gene consists of 13,604 bp, making it the largest of all the GH genes. The 5'
      flanking region within 697 bp contains consensus sequences for a TATA box, two
      Pit-1/GHF-1, three TRE, and a CRE. The sea lamprey GH gene consists of five exons
      and four introns, the same as in mammals, birds, and teleosts such as
      cypriniforms and siluriforms with the exception of some teleosts such as
      salmoniforms, percififorms, and tetradontiforms, in which there is an additional
      intron in the 5th exon. The 5-exon-type gene organization might reflect the
      structure of the ancestral gene for the GH/PRL/SL gene family.

PMID- 16288757
TI  - Regeneration and repair of peripheral nerves.
AB  - Posttraumatic nerve repair continues to be a major challenge in restorative
      medicine and microsurgery. Although progress has been made in surgical techniques
      over the last 30 years, functional recovery after a severe lesion of a major
      nerve trunk is often incomplete and often unsatisfactory. Functional recovery
      after surgical repair of mixed nerves is even more disappointing. Functional
      recovery after peripheral nerve lesion is dependent upon accurate regeneration of
      axons to their original target tissues. Thus, in order to enhance regeneration, a
      better understanding of the cellular and molecular biology of selective nerve
      regeneration is required. Schwann cells and their endoneurial extracellular
      matrix play pivotal roles in the selective promotion of motor and sensory axon
      regeneration. Knowledge of these mechanisms allows for the better development of
      biocompatible nerve grafting material.

PMID- 16288758
TI  - Tissue regeneration. The past, the present and the future.
AB  - Tissue engineering has been a topic of extensive research over the last years.
      The ability of human body to regenerate tissue loss such as bone, cartilage,
      nerves, skin and muscle is limited leading often to amputations of limbs or
      functional disability. The isolation of mesenchymal stem cells (MSCs) and later
      the embryonic stem cells in conjunction with the advances made in cellular
      biology, tissue engineering, genetics and recombinant technology has initiated
      the development of new techniques and new therapeutic strategies allowing
      treatment of many pathological conditions providing restoration of tissue
      continuity and function.

PMID- 16288759
TI  - Association between seroprevalence of anti-chlamydial antibodies and long-term
      cardiovascular mortality in chronic hemodialysis patients.
AB  - Chlamydial infection has been suspected in the pathogenesis of ischemic heart
      disease. However, it remains undetermined if persistent chlamydial infection is
      related to cardiovascular mortality in regular hemodialysis (HD) patients. We
      measured Chlamydia pneumoniae (Cp) antibody seropositivity in 154 HD subjects
      (age 59 +/- 11 years, time on HD 13 +/- 7 years, male/female = 101/53), and
      prospectively examined an association between Cp antibody status and
      cardiovascular death for 56 months of follow-up. Seropositivity for Cp IgA and
      IgG antibodies at the entry of the study was 50.6 and 60.8%, respectively. There
      was no significant difference in age, time on HD, serum albumin, C-reactive
      protein (CRP) and interleukin-6 (IL-6) between those positive and negative for
      IgA antibodies. During follow-up over 56 months, 31 patients (20.1%) expired, 16
      (55.2%) of them of cardiovascular causes. Serological IgA and IgG antibody
      positivity did not influence mortality, while multiple Cox proportional hazards
      analysis revealed that diabetes, ischemic changes on electrocardiogram, log
      transformed CRP and intact parathyroid hormone were independent determinants of
      cardiovascular death. These observations suggest that serological Cp antibody
      status does not affect long-term cardiovascular mortality in chronic HD patients.

PMID- 16288760
TI  - Impact of oxidized low density lipoprotein on vascular cells.
AB  - Oxidized LDL (OxLDL) is a proatherogenic lipoprotein, accumulating in the
      vascular wall and contributing to the pathogenesis of vascular dysfunction early
      in the development of atherosclerosis. Enhanced serum levels of OxLDL, as well as
      antibodies against its epitopes, are predictive for endothelial dysfunction and
      coronary heart disease. While enhanced oxidative stress is one factor triggering
      formation of OxLDL, OxLDL itself has been identified as a potent stimulus for
      vascular oxygen radical formation, causing a vicious circle. OxLDL-induced O(2)(
      ) formation, largely through activation of NADPH oxidase, but also through
      uncoupling of endothelial NO-synthase and through direct O(2)(-) release, leads
      to endothelial dysfunction. Furthermore, OxLDL-induced O(2)(-) formation has a
      strong impact on tissue remodeling, resulting in either cell growth -
      proliferation or hyperplasia - or apoptotic cell death. The effect of OxLDL on
      cell cycle regulation is mediated by activation of the small GTPase RhoA and
      consequent regulation of p27(KIP1), a key enzyme of the cell cycle. In addition,
      OxLDL-induced activation of RhoA sensitizes the contractile apparatus of the
      vessel wall, enhancing the contractile tonus and favoring vasospasm. Thus,
      through a variety of mechanisms, OxLDL importantly contributes to vascular
      dysfunction and remodeling.

PMID- 16288761
TI  - A novel method to estimate the stiffness of the equine back.
AB  - Diagnosis of back problems in equine orthopedics can be a difficult task. The aim
      of our study was to develop a new method for estimating the stiffness of the
      equine back in vivo. We measured the activity of the long back muscle at two
      locations on both sides at thoracic vertebrae T12 and T16 of 15 horses flexing
      and extending their back at stance using telemetric surface electromyography,
      while simultaneously recording the motion of the back with a video camera system.
      Out of these paired data sets we computed a transfer function in the frequency
      domain and evaluated its capability of capturing the biomechanical behavior. The
      transfer function was evaluated via correlation between calculated and actual
      motion resulting in correlation coefficients of 0.89 for lateral flexion and 0.83
      for ventral extension at T16 and 0.82 for lateral flexion and 0.83 for ventral
      extension at T12. The transfer function was fitted to a filter polynomial of
      second order, and related to the motion equation. By comparison of coefficients
      we gained an estimate for the stiffness of the back resulting in a mean value of
      approximately 6100 N/m for lateral flexion and 650 N/m for ventral extension.
      This new method enables clinicians in equine orthopedics to estimate back
      stiffness in horses, and it also provides reality grounded values for
      biomechanical models of the equine back.

PMID- 16288762
TI  - Determination of fluorescent whitening agents in environmental waters by solid
      phase extraction and ion pair liquid chromatography-tandem mass spectrometry.
AB  - A comprehensive method for the trace determination of four stilbene-type
      disulfonate and one distyrylbiphenyl-type fluorescent whitening agents (FWAs) in
      environmental water samples was developed and validated. Various solid-phase
      extraction (SPE) cartridges were investigated. The newly developed Oasis WAX
      (weak mixed-mode anion exchange and reversed-phase sorbent) SPE cartridge
      provides the optimal sample extraction results. The analytes were then identified
      and quantitated by liquid chromatography-electrospray ionization tandem mass
      spectrometry (HPLC-ESI-MS-MS) in negative ionization mode, applying di-n
      hexylammonium acetate (DHAA) as the ion-pairing reagent in mobile phase. Limits
      of quantitation (LOQs) were established between 4 and 18 ng/l in 50 ml of water
      samples. Intrabatch and interbatch precision with their accuracy at two
      concentration levels were also investigated. Precision for these five FWAs, as
      indicated by RSD, proved to be less than 13 and 11%, respectively, for intra- and
      interbatch. Accuracy, expressed as the mean recovery, was between 68 and 97%. The
      method was finally applied to environmental water samples, showing the occurrence
      of five FWAs in both river water and wastewater treatment plant (WWTP) effluent
      samples.

PMID- 16288763
TI  - Determination of the hydrolysis rate constants and activation energy of aesculin
      with capillary electrophoresis end-column amperometric detection.
AB  - Aesculetin is the product of the hydrolysis reaction of aesculin. A high
      sensitivity and good repeatability method based on capillary electrophoresis with
      amperometric detection (CE-AD) was developed for simultaneous determination of
      aesculin and aesculetin in the hydrolysate of aesculin. Under the optimum
      condition: 10mmol/L KH(2)PO(4)-5mmol/L Na(2)B(4)O(7) (pH 6.0) buffer, separation
      at 18kV and +900mV (versus Ag/AgCl) as the detection potential, the hydrolysis
      rate constants of aesculin hydrolysis at 25, 30, 35, 40 and 45 degrees C in
      0.1mol/L KOH were obtained as 1.45x10(-2)min(-1), 2.01x10(-2)min(-1), 2.93x10(
      2)min(-1), 3.76x10(-2)min(-1) and 5.05x10(-2)min(-1), respectively. It was
      calculated that the activation energy for aesculin hydrolysis was 49.4kJ/mol.

PMID- 16288764
TI  - Efficient new method for extraction and isolation of three flavonoids from
      Patrinia villosa Juss. by supercritical fluid extraction and high-speed counter
      current chromatography.
AB  - Supercritical fluid extraction (SFE) of orotinin, orotinin-5-methyl ether and
      licoagrochalcone B from Patrinia villosa was performed. The optimization of
      parameters including pressure, temperature, modifier and sample particle size on
      yield was carried out using an analytical-scale SFE system. The process was then
      scaled up by 100 times using a preparative SFE system under the optimized
      conditions of 25 MPa, 45 degrees C, a sample particle size 40-60 mesh and
      modified CO2 with 20% methanol. The yield of the preparative SFE was 2.82% (crude
      extract I) and the combined yield of orotinin, orotinin-5-methyl ether and
      licoagrochalcone B was 0.82 mg/g of dry sample mass. Then the crude extract I was
      re-dissolved in methanol and methanol soluble fraction (crude extract II, 0.17%)
      was obtained, which was successfully isolated and separated by a preparative high
      speed counter-current chromatography (HSCCC) with a two-phase solvent system
      composed of n-hexane-ethyl acetate-methanol-water (5:6:6:6, v/v/v/v) by
      increasing the flow-rate of the mobile phase stepwise from 1.0 to 2.0 ml/min
      after 3 h. The target compounds isolated and purified by HSCCC were analyzed by
      high performance liquid chromatography. The separation produced total of 38.2 mg
      of orotinin at 99.2% purity, 19.8 mg of orotinin-5-methyl ether at 98.5% purity
      and 21.5 mg of licoagrochalcone B at 97.6% purity from 400 mg of the crude
      extract in a one-step separation. The recoveries of orotinin, orotinin-5-methyl
      ether and licoagrochalcone B were 91.1, 91.6 and 90.3%, respectively, and the
      chemical structure identification was carried out by UV, IR, MS, 1H NMR and 13C
      NMR.

PMID- 16288765
TI  - Monitoring of the conversion from triptolide to tripchlorolide in Triptergium
      wilfordii by micellar electrokinetic caillary chromatography.
AB  - A novel concocting method to convert Triptolide (T) into Tripchlorolide (T(4)) in
      the traditional Chinese herb Tripterygium wilfordii Hook F. and a micellar
      electrokinetic capillary chromatographic (MEKC) approach by which the conversion
      of Triptolide (T) and Tripchlorolide (T(4)) was identified and determined had
      been established. Investigations of the influence of different pH values of boric
      acid and borax buffer and of sodium dodecyl sulfate (SDS) and organic additive
      concentrations had been carried out, and the optimum separation for T and T(4)
      was achieved using boric acid and borax of pH 7.0 with 30 mM SDS and 20% (volume
      ratio) methanol as the running buffer. It was found that MEKC exhibited good
      accuracy, precision and repeatability and the content of T(4) was greatly
      increased in the herb that was treated by the new concocting method.

PMID- 16288766
TI  - Rapid separation of Sudan dyes by reverse-phase high performance liquid
      chromatography through statistically designed experiments.
AB  - Central composite design (CCD) was effectively employed to decide optimum
      conditions for the rapid separation of Sudan dyes using reverse-phase high
      performance liquid chromatography (HPLC). Twenty experiments, taking the minimum
      resolution and retention time of the last eluted peak as the responses with three
      important factors, mobile phase composition, flow rate and column temperature,
      were used to design a mathematical model. The experimental responses were fitted
      into a second order polynomial and used to predict the optimum conditions for the
      effective separation of the studied compounds. Further, chromatographic
      separation efficiency was tested through generation of Pareto-optimal points. The
      validity of using modified central composite design in predicting the
      optimization conditions was experimentally verified. The optimum conditions were:
      acetonitrile/0.1% aqueous formic acid (90/10, %v/v) as the mobile phase, at a
      flow rate of 1.2mL/min and column temperature of 15 degrees C, respectively.
      While using this optimum condition, baseline separation with a minimum resolution
      more than 1.5 and a separation time of less than 6min were achieved.

PMID- 16288767
TI  - Size-exclusion chromatography of technical lignins in dimethyl sulfoxide/water
      and dimethylacetamide.
AB  - Well defined spent sulfite liquor samples and lignosulfonate fractions obtained
      by ultrafiltration were analyzed using size-exclusion chromatography. Two
      different eluent systems (dimethyl sulfoxide/water/lithium bromide;
      dimethylacetamide/lithium chloride) were compared regarding their suitability for
      lignin analysis. The differences of the elution profiles and calculated molar
      masses were discussed using conventional and universal calibration. For further
      validation four technical lignins from a Round Robin test were included into the
      study. The results indicated that both analytical systems under investigation
      were well suited for the analysis of technical lignins.

PMID- 16288768
TI  - Thermoplastic microchannel fabrication using carbon dioxide laser ablation.
AB  - We report the procedures of machining microchannels on Vivak co-polyester
      thermoplastic substrates using a simple industrial CO(2) laser marker. To avoid
      overheating the substrates, we develop low-power marking techniques in nearly
      anaerobic environment. These procedures are able to machine microchannels at
      various aspect ratios. Either straight or serpent channel can be easily marked.
      Like the wire-embossed channel walls, the ablated channel surfaces become charged
      after alkaline hydrolysis treatment. Stable electroosmotic flow in the charged
      conduit is observed to be of the same order of magnitude as that in fused silica
      capillary. Typical dynamic coating protocols to alter the conduit surface
      properties are transferable to the ablated channels. The effects of buffer
      acidity on electroosmotic mobility in both bare and coated channels are similar
      to those in fused silica capillaries. Using video microscopy we also demonstrate
      that this device is useful in distinguishing the electrophoretic mobility of bare
      and latex particles from that of functionalized ones.

PMID- 16288769
TI  - Quantitative study of the structure-retention index relationship in the imine
      family.
AB  - The Kovats retention index is one of the most popular descriptors of the
      performance of organic compounds in gas chromatography (GC). The mathematical
      modeling of this index is an interesting and open problem in analytical
      chemistry. In this paper, two models for the prediction of the Kovats retention
      index are presented. Topologic, topographic and quantum-chemical descriptors were
      used as structural descriptors. Multiple linear regression (MLR) analysis
      provides the first model using the forward stepwise procedure for the variable
      selection. For the second one, an ensemble of artificial neural network (ANN) was
      constructed using the pruning algorithm. Both methods were validated by an
      external set of compounds, by the Golbraikh and Tropsha method and by the leave
      one-out (LOO) and the leave many out (LMO) procedures. The R2, RMScv and Q2,
      values for the training sets were 0.884, 0.589 and 0.830 for NN and 0.974, 0.417
      and 0.970 for MLR models, respectively. The robustness of both models was
      demonstrated. Both portrait the chromatographic performance of the sample but in
      this case, the results of MLR equation are better than the NN ones. The MLR model
      is recommended because of its simplicity.

PMID- 16288770
TI  - Miniaturized thermal lens and fluorescence detection system for microchemical
      chips.
AB  - We have developed a miniaturized two-way detection system using thermal lens and
      fluorescence spectroscopies for microchip chemistry. The system was composed of
      laser diode (LD) modules, fiber-based optics combined with a gradient index lens,
      and miniaturized detection units for thermal lens and fluorescence signals. The
      detection limits in the thermal lens and fluorescence spectroscopies were 6.3 x
      10(-9)M for Ni(II) phthalocyanine tetrasulfonic acid and 3.0 x 10(-9)M for cy5,
      respectively. The performance of the system with the miniaturized thermal lens
      was equivalent to that of a conventional thermal lens microscope. The
      fluorescence sensitivity was comparable to sensitivities offered by conventional
      miniaturized systems.

PMID- 16288771
TI  - Differential capacitance of liquid/liquid interfaces--a lattice gas model
      approach.
AB  - A lattice gas model formalism under mean field approximation is developed for the
      analysis of differential capacitance pertaining to liquid/liquid interfaces. The
      interfacial profiles for the two solvent mole fractions are chosen and ionic
      charge densities are estimated by minimizing the Helmholtz free energy. The
      dependence of the differential capacitance on various interaction energies,
      electrolyte concentrations and dielectric constants is indicated. The influence
      of the solvent density profile is analyzed and deviations from the predictions of
      Gouy-Chapman theory are pointed out.

PMID- 16288772
TI  - Effect of the crosslinking degree and the nickel salt load on the thermal
      decomposition of poly(2-hydroxyethyl methacrylate) hydrogels and on the metal
      release from them.
AB  - Polymeric matrices of poly(2-hydroxyethyl methacrylate) (PHEMA) crosslinked with
      different percentages of ethylene glycol dimethacrylate (EGDMA) as well as
      different loads of nickel salt were synthesized. Nickel release from the
      polymeric systems, and their thermal stability were analyzed. A high percentage
      of the nickel loaded was released, although strong interactions between the
      polymeric matrices and the nickel ion must be established since a total nickel
      release did not take place. The values of the diffusion coefficients showed that
      nickel release depended on the amount of nickel salt loaded in the polymeric
      matrix and also on the crosslinking degree of the gels. On the other hand, the
      presence of nickel salt induced an evident thermal instability in the polymeric
      matrices, although all the polymeric systems can be considered thermally stable.

PMID- 16288773
TI  - WITHDRAWN: Interlayer structure and morphology of HDTMA(+)/montmorillonite
      organoclay.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 16288774
TI  - Chemical preparation of Pd nanoparticles in room temperature ethylene glycol
      system and its application to electroless copper deposition.
AB  - Room-temperature synthesis of Pd nanoparticles protected by polyvinylpyrrolidone
      (PVP) has been successfully achieved by merely adding sodium hydroxide (NaOH)
      acting as accelerator for the reduction of Pd(II) in ethylene glycol (EG) without
      any externally added reducing agent. The Pd particle sizes were controlled in the
      range from 8.6 to 2.4 nm by changing the concentration of NaOH from 0 to 3.2x10(
      1) M. The particle formation was monitored by UV-vis spectroscopy and the
      microstructure of Pd nanoparticles was analyzed by TEM and XRD. The product of
      adding NaOH in EG was characterized by FTIR and a -CHO group which possesses
      reductive ability was identified. In addition, the prepared Pd nanoparticle could
      serve as an effective activator for electroless copper deposition (ECD) on epoxy
      substrate, which is an essential process in the printed circuit board (PCB)
      industry. In contrast to existing commercial activators, the new activator shows
      superior stability and excellent performance for ECD.

PMID- 16288775
TI  - An in situ ATR-FTIR study of polyacrylamide adsorption at the talc surface.
AB  - The adsorption of a low molecular weight unmodified polyacrylamide (Polymer-N)
      and a hydroxyl-substituted polyacrylamide (Polymer-H) onto talc was studied using
      in situ particle film ATR-FTIR spectroscopy in the multiple internal reflection
      mode. Spectra of the adsorbed polymer were collected as a function of increasing
      concentration and as a function of time. Measurement of the peak intensities of
      the adsorbed polymer allowed adsorption isotherms and adsorption kinetics to be
      determined for both polymers. Langmuir adsorption isotherm analysis of in situ
      data yielded Gibbs free energies of adsorption (deltaG0(ads)) for Polymer-N and
      Polymer-H of -44.5 and -45.7 kJ/mol, respectively, which correlate well with
      similar values determined from ex situ adsorption isotherms. Kinetic analysis
      indicated that the adsorption of both polymers was a pseudo-first-order process.
      The apparent rate constants for Polymer-N and Polymer-H were 0.10 and 0.15 min(
      1), respectively. Absence of spectral shifts in the spectra of adsorbed polymer
      is indicative of a hydrophobic interaction between the polyacrylamides and the
      talc surface.

PMID- 16288776
TI  - Prolonged oxidative stress inverts the cardiac force-frequency relation: role of
      altered calcium handling and myofilament calcium responsiveness.
AB  - The normally positive force- and Ca2+ -frequency responses (FFR and CaFR) are
      inverted in heart failure (HF); whether oxidative stress contributes to these
      abnormalities is unknown. We evaluated the impact of acute and prolonged
      oxidative stress on contraction and Ca2+ handling in adult rat cardiomyocytes.
      Acute (30 min) exposure to H2O2 (100 microM) induced a twofold increase (P<0.025)
      in intracellular oxyradicals together with contractile depression despite
      preservation of the Ca2+ transient and the FFR and CaFR to 3 Hz, indicating
      reduced myofilament Ca2+ responsiveness. In contrast, prolonged (24 h) exposure
      to the copper-zinc superoxide dismutase inhibitor diethyldithiocarbamic acid
      (DDC, 1 microM) similarly augmented oxyradicals but also increased cell size, and
      contraction and Ca2+ transient duration (P<0.025). DDC-treated myocytes displayed
      inverted FFRs and attenuated (though still positive) CaFRs as compared to
      control, indicating reduced myofilament Ca2+ responsiveness coupled with altered
      Ca2+ handling. Protein levels of the Na+ -Ca2+ exchanger (NCX), sarcoplasmic
      reticular (SR) Ca2+ ATPase (SERCA2), and serine-16 phosphorylated phospholamban
      (pSer16-PLB) were increased (P<0.025), whereas dihydropyridine receptor abundance
      was decreased. Total PLB and ryanodine receptor protein expression were
      unchanged. Caffeine-induced Ca2+ release showed increased NCX activity (P<0.025)
      without changes in total releasable SR Ca2+, suggesting compensatory changes in
      SERCA2 and pSer16-PLB to maintain SR Ca2+ load. The superoxide scavenger Tiron
      attenuated these effects. Thus, acute oxyradical exposure rapidly depresses
      myofibrillar Ca2+ responsiveness. Prolonged oxidative stress further induces
      alterations in Ca2+ handling that combined with extant reductions in myofibrillar
      responsiveness invert the FFR. With regard to Ca2+ handling, reduced
      transsarcolemmal Ca2+ flux rather than reduced SR Ca2+ uptake was the primary
      determinant of a negative FFR. Analogous changes may be operative in HF, a state
      characterized by both oxidative stress and Ca2+ dysregulation.

PMID- 16288777
TI  - The ubiquitous role of nitric oxide in cardioprotection.
AB  - In recent years, major advances have been made toward understanding the role of
      nitric oxide (NO) in the ischemic biology of the heart. It is now clear that NO,
      either endogenous or exogenous, represents one of the most important defenses
      against myocardial ischemia-reperfusion injury. The purpose of this review is to
      provide an update on the cardioprotective actions of NO, with particular emphasis
      on the function of the inducible isoform of NO synthase (iNOS) and on the role of
      mitochondria in NO-mediated protection. This essay underscores some of the more
      prominent areas of ischemic biology that relate to NO, such as ischemic
      preconditioning, pharmacological cardioprotection, and gene therapy. The
      hypothesis that the late phase of preconditioning is mediated by increased iNOS
      activity resulting in enhanced NO bioavailability, first proposed by our group,
      is now widely accepted and can be regarded as a proven hypothesis. Likewise, the
      burgeoning field of postconditioning may share such a requirement for NO. Various
      drugs (e.g. statins, ACE inhibitors, angiotensin-receptor blockers, etc.) also
      produce salubrious effects in experimental models of myocardial infarction via
      their enhancement of NO bioavailability. Thus, NO appears to be a common mediator
      of the protection afforded by a wide array of seemingly unrelated pharmacological
      and nonpharmacological interventions, underscoring its fundamental role as a
      ubiquitous defense of the heart against ischemia and reperfusion. This review
      challenges the conventional wisdom that iNOS is deleterious during myocardial
      ischemia-reperfusion and instead proposes the concept that iNOS, when expressed
      in cardiac myocytes, is a profoundly protective protein. We also emphasize the
      emerging importance of the mitochondrial actions of NO. Although the precise
      molecular events remain to be defined, we propose that NO interacts with
      components of the electron transport chain and/or the mitochondrial permeability
      transition pore to limit post-ischemic myocardial damage, and that this action
      potentially provides a fundamental molecular explanation for the mechanism of NO
      mediated cardioprotection.

PMID- 16288778
TI  - Intermittent high altitude hypoxia inhibits opening of mitochondrial permeability
      transition pores against reperfusion injury.
AB  - The role of mitochondrial permeability transition pore (MPTP) in the mechanism of
      intermittent high altitude (IHA) hypoxic adaptation is not understood. Therefore,
      we study whether the protective effect of IHA hypoxia against ischemia
      reperfusion injury is accompanied by inhibition of MPTP opening. IHA hypoxia
      significantly improved the functional recovery of Langendorff hearts on
      reperfusion and limited infarct size. In isolated myocytes, IHA hypoxia
      significantly improved the recovery of cell length, lowered ischemia-reperfusion
      induced [Ca2+]c and [Ca2+]m overloading. Furthermore, IHA hypoxia accelerated
      [Ca2+]c decline during reperfusion. Opening the MPTP with atractyloside
      immediately at reperfusion abolished these cardioprotective effects of IHA
      hypoxia, but had no appreciable influence on those of normoxic hearts. IHA
      hypoxia prolongs the time taken to induce MPTP opening and the time taken to
      induce rigor contracture when myocytes subjected to oxidative stress. The data
      from isolated mitochondria demonstrated that IHA hypoxia prevented the decrease
      of ADP/O ratio, the opening of MPTP and the release of cytochrome c from
      mitochondria at high Ca2+ concentrations (100 and 200 microM). Inhibition of MPTP
      opening in the first few minutes of reperfusion accelerated [Ca2+]c decline and
      attenuated [Ca2+]c and [Ca2+]m overloading, which contributed to the
      cardioprotection of IHA hypoxic adaptation. Enhancement of the tolerance of
      mitochondria against Ca2+ might underlie the protective mechanism of IHA hypoxia.

PMID- 16288779
TI  - Transplantation of embryonic stem cells into the infarcted mouse heart: formation
      of multiple cell types.
AB  - Initial studies have suggested that transplantation of embryonic stem (ES) cells
      following myocardial infarction (MI) in animal models is beneficial; however, the
      mechanism of benefit is largely unknown. The present study investigated the fate
      of mouse ES cells transplanted post-MI to determine if the ES cells give rise to
      the range of major cell types present in the native myocardium. MI was produced
      by coronary artery ligation in C57BL/6 mice. Two different mouse ES cell lines,
      expressing eGFP and beta-galactosidase, respectively, were tested. Post-MI
      intramyocardial injection of 3 x 10(4) ES cells was compared to injection of
      media alone. Histochemistry and immunofluorescence were used to track the
      transplanted ES cells and identify the resulting cell types. Echocardiography
      assessed the cardiac size and function in a blinded fashion. Two weeks post-MI,
      engraftment of the transplanted ES cells was demonstrated by eGFP or beta
      galactosidase-positive cells in the infarct region without evidence for tumor
      formation. Co-immunolabeling demonstrated that the transplanted ES cells had
      become cardiomyocytes, vascular smooth muscle, and endothelial cells.
      Echocardiographic analysis showed that ES cell transplantation resulted in
      reduced post-MI remodeling of the heart and improved cardiac function. In
      conclusion, transplanted mouse ES cells can regenerate infarcted myocardium in
      part by becoming cardiomyocytes, vascular smooth muscle, and endothelial cells
      that result in an improvement in cardiac structure and function. Therefore, ES
      cells hold promise for myocardial cellular therapy.

PMID- 16288780
TI  - Mechanism of cardioprotection following trauma-hemorrhagic shock by a selective
      estrogen receptor-beta agonist: up-regulation of cardiac heat shock factor-1 and
      heat shock proteins.
AB  - Although 17beta-estradiol (E2) administration following trauma-hemorrhage (T-H)
      improves cardiac function in male rodents, it is not known whether the salutary
      effects of E2 are mediated via estrogen receptor (ER)-alpha or ER-beta, and
      whether cardiac heat shock proteins (Hsp) are affected by E2 administration. Male
      Sprague-Dawley rats underwent T-H (mean BP 40 mmHg for 90 min, then
      resuscitation). ER-alpha agonist propyl pyrazole triol (PPT) (5 microg/kg), ER
      beta agonist diarylpropiolnitrile (DPN) (5 microg/kg), or vehicle (10% DMSO) was
      injected subcutaneously during resuscitation. At 24 h after T-H or sham
      operation, cardiac output (CO), stroke volume (SV), mean blood pressure, and +/-
      dP/dt max were measured (n=6 rats per group). Cardiac Hsp32, 60, 70, and 90
      mRNA/protein expressions and heat shock factor (HSF)-1 DNA binding activity were
      determined. One-way ANOVA and Tukey's test were used for statistical analysis.
      CO, SV and +/- dP/dt(max) decreased significantly after T-H, however,
      administration of ER-beta agonist DPN after T-H restored the above parameters.
      Moreover, DPN treatment prevented T-H-mediated decrease in Hsp60 mRNA/protein and
      Hsp90 protein expressions in the heart. Hsp32 and Hsp70 mRNA/protein expression
      and HSF-1 DNA binding activity in the hearts were increased even above the shams
      in DPN treated T-H rats. In contrast, no significant change in the above
      parameters was observed in T-H rats treated with ER-alpha agonist PPT. Thus, the
      salutary effects of E2 on cardiac function are mediated via ER-beta and ER-beta
      induced up-regulation of Hsp likely plays a significant role in the E2-mediated
      cardioprotection after T-H.

PMID- 16288781
TI  - Structural studies of an engineered zinc biosensor reveal an unanticipated mode
      of zinc binding.
AB  - Protein engineering was used previously to convert maltose-binding protein (MBP)
      into a zinc biosensor. Zn(2+) binding by the engineered MBP was thought to
      require a large conformational change from "open" to "closed", similar to that
      observed when maltose is bound by the wild-type protein. We show that although
      this re-designed MBP molecule binds Zn(2+) with high affinity as previously
      reported, it does not adopt a closed conformation in solution as assessed by
      small-angle X-ray scattering. High-resolution crystallographic studies of the
      engineered Zn(2+)-binding MBP molecule demonstrate that Zn(2+) is coordinated by
      residues on the N-terminal lobe only, and therefore Zn(2+) binding does not
      require the protein to adopt a fully closed conformation. Additional
      crystallographic studies indicate that this unexpected Zn(2+) binding site can
      also coordinate Cu(2+) and Ni(2+) with only subtle changes in the overall
      conformation of the protein. This work illustrates that the energetic barrier to
      domain closure, which normally functions to maintain MBP in an open concentration
      in the absence of ligand, is not easily overcome by protein design. A comparison
      to the mechanism of maltose-induced domain rearrangement is discussed.

PMID- 16288782
TI  - Life-history evolution and the origin of multicellularity.
AB  - The fitness of an evolutionary individual can be understood in terms of its two
      basic components: survival and reproduction. As embodied in current theory, trade
      offs between these fitness components drive the evolution of life-history traits
      in extant multicellular organisms. Here, we argue that the evolution of germ-soma
      specialization and the emergence of individuality at a new higher level during
      the transition from unicellular to multicellular organisms are also consequences
      of trade-offs between the two components of fitness-survival and reproduction.
      The models presented here explore fitness trade-offs at both the cell and group
      levels during the unicellular-multicellular transition. When the two components
      of fitness negatively covary at the lower level there is an enhanced fitness at
      the group level equal to the covariance of components at the lower level. We show
      that the group fitness trade-offs are initially determined by the cell level
      trade-offs. However, as the transition proceeds to multicellularity, the group
      level trade-offs depart from the cell level ones, because certain fitness
      advantages of cell specialization may be realized only by the group. The
      curvature of the trade-off between fitness components is a basic issue in life
      history theory and we predict that this curvature is concave in single-celled
      organisms but becomes increasingly convex as group size increases in
      multicellular organisms. We argue that the increasingly convex curvature of the
      trade-off function is driven by the initial cost of reproduction to survival
      which increases as group size increases. To illustrate the principles and
      conclusions of the model, we consider aspects of the biology of the volvocine
      green algae, which contain both unicellular and multicellular members.

PMID- 16288783
TI  - Lymphocyte cytochrome c oxidase, cyclic GMP and cholinergic muscarinic receptors
      as peripheral indicators of carbon monoxide neurotoxicity after acute and
      repeated exposure in the rat.
AB  - Changes in cerebral cytochrome oxidase (COX) activity, nitric oxide (NO)-cyclic
      GMP (cGMP) pathway and cholinergic muscarinic receptors (MRs) have been reported
      in rodents acutely exposed to carbon monoxide (CO). These endpoints measurable in
      lymphocytes may serve as peripheral markers of CO neurotoxicity. The early and
      delayed effects of repeated and acute in vivo CO inhalation were investigated on
      COX activity, cGMP formation and MR binding in rat brain and lymphocytes to
      assess whether each endpoint was similarly affected both centrally and
      peripherally. Male Wistar rats either inhaled 500 ppm CO, 6 h/day, 5 days/week, 4
      weeks (repeated exposure) or 2,400 ppm, 1 h (single exposure). Neither treatment
      altered brain or lymphocyte COX activity 1 and 7 days post-treatment. Also
      ineffective were repeated and acute CO treatments towards (3)H-quinuclidinyl
      benzilate (QNB) binding to MRs in cerebral cortex, hippocampus, striatum,
      cerebellum (respective controls, mean+/-S.D.: 171 +/- 45, 245 +/- 53, 263 +/- 14
      and 77 +/- 7 fmol/mg protein) and lymphocytes (24 +/- 10 fmol/million cells) at
      the same time points. In lymphocytes control cGMP levels averaged 1.98 +/- 0.99
      pmol/mg protein under basal conditions, and 3.94 +/- 0.55 pmol/mg protein after
      NO-stimulation. One day after chronic treatment cessation, the CO-treated group
      displayed about a 50% decrease in both basal and NO-stimulated cGMP values, which
      persisted up to 7 days after, compared to air-exposed rats. Acutely, CO caused a
      delayed enhancement (+140%) of NO-induced activation of soluble guanylate
      cyclase. The finding that the NO-cGMP pathway is a target for the delayed effects
      of CO in peripheral blood cells is in accordance with our data in brain
      [Hernandez-Viadel, M., Castoldi, A.F., Coccini, T., Manzo, L., Erceg, S., Felipo,
      V., 2004. In vivo exposure to carbon monoxide causes delayed impairment of
      activation of soluble guanylate cyclase by nitric oxide in rat brain cortex and
      cerebellum. Journal of Neurochemistry 89, 1,157-1,165], and supports the use of
      this peripheral endpoint as a biomarker of CO central effects.

PMID- 16288784
TI  - Selective protection of curcumin against carbon tetrachloride-induced
      inactivation of hepatic cytochrome P450 isozymes in rats.
AB  - We investigated the effects of curcumin, a major antioxidant constituent of
      turmeric, on hepatic cytochrome P450 (CYP) activity in rats. Wistar rats received
      curcumin-containing diets (0.05, 0.5 and 5 g/kg diet) with or without injection
      of carbon tetrachloride (CCl(4)). The hepatic CYP content and activities of six
      CYP isozymes remained unchanged by curcumin treatment, except for the group
      treated with the extremely high dose (5 g/kg). This suggested that daily dose of
      curcumin does not cause CYP-mediated interaction with co-administered drugs.
      Chronic CCl(4) injection drastically decreased CYP activity, especially CYP2E1
      activity, which is involved in the bioactivation of CCl(4), thereby producing
      reactive free radicals. Treatment with curcumin at 0.5 g/kg alleviated the CCl(4)
      induced inactivation of CYPs 1A, 2B, 2C and 3A isozymes, except for CYP2E1. The
      lack of effect of curcumin on CYP2E1 damage might be related to suicidal radical
      production by CYP2E1 on the same enzyme. It is speculated that curcumin inhibited
      CCl(4)-induced secondary hepatic CYPs damage through its antioxidant properties.
      Our results demonstrated that CYP isozyme inactivation in rat liver caused by
      CCl(4) was inhibited by curcumin. Dietary intake of curcumin may protect against
      CCl(4)-induced hepatic CYP inactivation via its antioxidant properties, without
      inducing hepatic CYPs.

PMID- 16288785
TI  - Pharmacokinetics of oltipraz in rat models of diabetes mellitus induced by
      alloxan or streptozotocin.
AB  - Pharmacokinetic parameters of oltipraz were compared after intravenous (10 mg/kg)
      and oral (30 mg/kg) administration in rat model of diabetes mellitus induced by
      alloxan (rat model of DMIA) or streptozotocin (rat model of DMIS) and their
      respective control male Sprague-Dawley rats. In rat models of DMIA and DMIS, the
      expressions and mRNA levels of CYP1A2, 2B1/2, and 3A1(23) increased, and oltipraz
      was metabolized mainly via CYP1A1/2, 2B1/2, 2C11, 2D1, and 3A1/2 in male Sprague
      Dawley rats. Hence, it would be expected that the AUC and CL values of oltipraz
      would be significantly smaller and faster, respectively, in rat models of
      diabetes. This was proven by the following results. After intravenous
      administration, the AUC values were significantly smaller in rat models of DMIA
      (40.1% decrease) and DMIS (26.0% decrease) than those in respective control rats,
      and this could be due to significantly faster CL values in rat models of DMIA
      (40.1% increase) and DMIS (26.0% increase). The faster CL could be due to
      increase in hepatic blood flow rate and significantly faster CL(int) in rat
      models of diabetes, since oltipraz is an intermediate hepatic extraction ratio
      drug in male Sprague-Dawley rats. After oral administration, the AUC values of
      oltipraz were also significantly smaller in rat models of DMIA (54.0% decrease)
      and DMIS (63.2% decrease). This could be due to increase in hepatic blood flow
      rate, significantly faster CL(int), and changes in the intestinal first-pass
      effect in rat models of diabetes. However, this was not due to decrease in
      absorption in rat models of diabetes.

PMID- 16288786
TI  - Can industrial pollution cause intersexuality in the amphipod, Echinogammarus
      marinus?
AB  - Following recent studies, in which intersex and/or reproductive abnormalities
      have been observed in a number of crustaceans in association with pollution, the
      prevalence of intersexuality in the amphipod, Echinogammarus marinus was
      monitored at sites receiving industrial discharges for one year in 2002/2003.
      Based upon reports of intersexuality occurring in amphipods due to feminising
      microsporidian parasites, the occurrence, and role of microsporidian parasites in
      causing intersex was investigated through histological examination. Results
      demonstrate a significantly higher prevalence of intersex organisms was found at
      sites receiving industrial discharges throughout the year when compared to a
      reference site, with the phenotype of intersex (intersex male and intersex
      female) varying in its dominance between impacted sites. Intersex specimens were
      significantly more likely to be infected with microsporidian parasites at sites
      receiving discharges than reference sites, however relatively few specimens
      (normal or intersex) were infected at reference sites suggesting parasitism is
      not the only cause of intersex. The direct/indirect role of pollution in the
      observed intersexuality is discussed.

PMID- 16288787
TI  - Polychlorinated biphenyls and DDT residues distribution in sediments of Cortiou
      (Marseille, France).

PMID- 16288788
TI  - Iridoid glucosides from Kickxia abhaica D.A. Sutton from Scrophulariaceae.
AB  - Two iridoid glucosides namely; 6-acetylantirrinoside (1), 6'-O-p
      hydroxybenzoylantirrinoside (2) were isolated from the aerial parts of Kickxia
      abhaica. Beside that, three known iridoid glucosides, antirrinoside (3),
      antirride (4) and mussaenosidic acid (5), one flavone glycoside (6) and a
      hexitol, d-mannitol (7) were isolated. The structures of the iridoid glucosides 1
      2 were established by 1D and 2D NMR spectral data, including COSY, HMQC and HMBC
      experiments, as well as HRMS.

PMID- 16288789
TI  - Parasite density and impaired biochemical/hematological status are associated
      with severe clinical aspects of canine visceral leishmaniasis.
AB  - We have performed a detailed investigation in 40 dogs naturally infected with
      Leishmania infantum (syn. chagasi), subdivided into three groups: asymptomatic
      (AD = 12), oligosymptomatic (OD = 12) and symptomatic (SD = 16), based on their
      clinical features. Twenty non-infected dogs (CD) were included as control group.
      Serological analysis, performed by IFAT and ELISA, demonstrated higher antibodies
      titers in SD in comparison to the AD. A positive correlation was found between
      parasite density in the spleen and skin smears as well as the bone marrow
      parasitism with clinical status of the infection. We observed that the
      progression of the disease from asymptomatic to symptomatic clinical form was
      accompanied by intense parasitism in the bone marrow. It is likely that this led
      to the impaired biochemical/hematological status observed. Finally, we believe
      that the follow-up of these parameters could be a relevant approach to be used as
      markers during therapeutic and vaccine evaluations.

PMID- 16288790
TI  - An efficient PCR--SSCP-based method for detection of a chloroquine resistance
      marker in the PfCRT gene of Plasmodium falciparum.
AB  - The spread of chloroquine resistance throughout the world poses a major problem
      in combating malaria. In the present study, an efficient polymerase chain
      reaction-single strand conformational polymorphism (PCR--SSCP)-based assay
      detected the PfCRT K76T point mutation, which is a marker for chloroquine
      resistance. For the first time, we have used a PCR--SSCP-based technique to
      identify the mutation in a single-step labelling reaction during PCR and SSCP gel
      electrophoresis. This assay is 100% efficient, giving no false-positive or 
      negative results, and can be carried out within a short bench time. We have
      successfully analysed 120 natural isolates using the PCR-SSCP method for
      detection of the chloroquine resistance marker and found 91 of the 120 samples to
      show the PfCRT T76 mutation, and 71% (65 of the 91 samples) showed a positive
      correlation with chloroquine resistance from the clinical data of the patients.
      The PCR-SSCP technique can also be applied for the detection of new haplotypes of
      the PfCRT gene and surveillance of chloroquine-resistant malaria in malaria
      endemic localities around the world.

PMID- 16288791
TI  - Genetic diversity of T-helper cell epitopic regions of circumsporozoite protein
      of Plasmodium falciparum isolates from India.
AB  - Genetic variation in the T-helper cell epitopic regions (Th2R and Th3R) of
      circumsporozoite protein of 135 Plasmodium falciparum isolates collected from
      different epidemic and endemic regions of India was studied. Variation in the
      Th2R and Th3R regions was found to exhibit restricted polymorphism and can be
      grouped. The variations were not regionally biased, as different isolates
      collected from different regions were found to belong to the same group. The Th2R
      and Th3R sequences were found to be linked in each isolate. Since the variations
      are regionally unbiased and restricted, the prototype variant from the groups
      could be included in a subunit polyvalent vaccine against sporozoites.

PMID- 16288792
TI  - Adverse reactions following mass drug administration during the Programme to
      Eliminate Lymphatic Filariasis in Orissa State, India.
AB  - The frequency and severity of adverse reactions are the main reasons for low
      compliance of mass drug administration (MDA) under the Programme to Eliminate
      Lymphatic Filariasis (PELF). This paper reports the frequency and types of
      adverse reactions during two MDAs during January 2002 and September 2004 in the
      State of Orissa, India. Of the people who consumed the drugs, 15.5% in the 2002
      MDA and 16.5% in the 2004 MDA reported one or more adverse reactions. This rate
      is higher (49.7%) in a group of individuals who were monitored for 6 days from
      the day of consumption of drugs during the 2002 MDA. However, many of these
      reactions were mild. No significant difference was found in the frequency of
      adverse reactions between MDA with diethylcarbamazine (DEC) alone and with DEC
      and albendazole. Significant gender differences were found in the 2004 MDA but no
      such differences were found in the 2002 MDA; however, the frequency of adverse
      reactions increased with age. Of all the adverse reactions, systemic adverse
      reactions typically associated with microfilarial death were more frequent. The
      frequency of adverse reactions was higher in microfilaraemics compared with
      amicrofilaraemic controls. The present study warrants developing an active
      adverse reaction surveillance system to minimise the impact of adverse reactions
      on MDA compliance.

PMID- 16288793
TI  - The comparison of spatially separated colours.
AB  - We have measured chromatic discrimination as a function of the spatial separation
      of the stimuli within the visual field. Pairs of stimuli were presented on an
      imaginary circle of 5 degrees radius and the distance between their centres was
      varied up to 10 degrees. Stimulus duration was 100 ms. Constructing an analogue
      of the MacLeod-Boynton diagram for an extra-foveal observer, we made separate
      series of measurements for the L/(L+M) and S/(L+M) axes of colour space. For both
      these axes, discrimination was optimal when there was a small spatial interval
      between the boundaries of the stimuli; thereafter thresholds rose moderately with
      increasing separation. Nevertheless, even at a separation of 10 degrees ,
      subjects exhibited impressive discrimination, achieving thresholds in the range
      0.4-2% on the L/(L+M) axis and in the range 3-6% on the S/(L+M) axis. Even when
      the two stimuli fell in different hemifields and transmission of information
      across the corpus callosum was required, accuracy did not differ significantly
      from that obtained when both stimuli fell within one hemifield. The human ability
      to compare remote stimuli requires an explanation. We argue that the
      discrimination is unlikely to depend on hard-wired neural comparators and may
      depend on neural representations that can be transmitted on a cerebral bus
      independently of the particular neurons carrying the code. Contrary to earlier
      reports, chromatic discrimination was not systematically better in the left
      visual field than in the right. And only one subject showed a significant
      advantage of the lower hemifield over the upper hemifield.

PMID- 16288795
TI  - Inhibition of calcite crystal growth by polyphosphates.
AB  - The inhibition of calcite crystal growth by pyrophosphate (P(2)O(7)(4-)),
      tripolyphosphate (P(3)O(10)(5-)), hexametaphosphate (P(6)O(18)(6-)) and binary
      polyphosphate blends in calcite-seeded solutions was investigated with various
      solution compositions using a pH-stat system. In a single polyphosphate system,
      tripolyphosphate was found to be the strongest inhibitor, followed by
      pyrophosphate and hexametaphosphate. The inhibition can be explained by the
      adsorption of polyphosphates on the calcite surface conforming to a simple
      Langmuir adsorption model. Through a detailed speciation analysis, CaP(2)O(7)(2-)
      and CaP(3)O(10)(3-) were found to be the primary species of pyrophosphate and
      tripolyphosphate responsible for adsorption of phosphate on the calcite surface,
      while the responsible species for hexametaphosphate could not be determined
      because of a lack of published stability constants. By comparing the equilibrium
      constants for the adsorption reaction, the inhibitory capabilities of
      polyphosphates are about two orders of magnitude greater than that of
      orthophosphate. In binary-polyphosphate systems, the inhibition of calcite
      crystal growth can be described by a competitive Langmuir adsorption model using
      the stability constants derived from single solute systems. The inhibitory
      behavior of commercially available phosphate blends that are marketed to prevent
      calcite scale formation were demonstrated to be similar to those of laboratory
      prepared blends with the same chemical composition.

PMID- 16288796
TI  - DPB formation in breakpoint chlorination of wastewater.
AB  - The formation of trihalomethanes (THMs) and haloacetic acids (HAAs), two major
      disinfection by-products (DBPs), from the breakpoint chlorination of three
      diluted yet buffered (pH 7.0) wastewater effluents was studied. The
      concentrations and distributions of THMs and HAAs species varied among different
      effluents at different zones of the breakpoint curves. Nevertheless, some common
      trends were observed. The formation of chloro-only THMs and HAAs, after
      normalization with the carbon contents of the effluents, increased with
      increasing the specific UV absorbance (SUVA) of the effluents but the dependency
      is not valid for bromo- or bromochloro-DBPs. The formation of THMs and HAAs
      showed no significant inclination with increasing chlorine dosages up to the
      breakpoint, but increased sharply beyond the breakpoint dosing level. Bromine
      incorporations into THMs and HAAs increased with an increasing bromide to DOC
      molar ratio. In addition, the bromine incorporation was also found to be highly
      dependent on the chlorine dosage and the bromide to ammonia ratio. A longer
      reaction time increased the yields of THMs and HAAs and was found to favor the
      formation of dihalogenated HAAs. A two-stage correlation between the total THMs
      and the total HAAs was found for each wastewater effluent.

PMID- 16288797
TI  - Heap leaching of Pb and Zn contaminated soil using ozone/UV treatment of EDTA
      extractants.
AB  - The feasibility of a novel EDTA-based soil heap leaching method with treatment
      and reuse of extractants in a closed process loop was evaluated on a laboratory
      scale. Ozone and UV irradiation were used for oxidative decomposition of EDTA
      metal complexes in extractants from Pb (1243 mg kg(-1)) and Zn (1190 mg kg(-1))
      contaminated soil. Released metals were absorbed in a commercial metal absorbent
      Slovakite. Six-consecutive additions of 2.5 mmol kg(-1) EDTA (total 15 mmol kg(
      1) EDTA) removed 49.6 +/- 0.6% and 19.7 +/- 1.7% of initial total Pb and Zn from
      soil (4.6 kg) packed in 22 cm high columns. The efficiency of extraction was
      similar to small-scale simulations of heap leaching (15 0 g of soil), where EDTA
      used in the same manner removed 49.7 +/- 1.0% and 13.7 +/- 0.4% of Pb and Zn. The
      new heap leaching method produced discharge extractant with fairly low final
      concentrations of Pb, Zn and EDTA (1.98 +/- 2.17 mg l(-1), 4.55 +/- 2.36 mg l(
      1), and 0.05 +/- 0.04 mM, respectively), which could presumably be reduced even
      further with continuation of treatment. The results of our study indicate that
      for soils contaminated primarily with Pb, treating the EDTA extractants with
      ozone/UV and reuse of extractants enables efficient soil heap leaching with very
      little or no wastewater generation, easy control over emissions, and lowers the
      requirements for process water.

PMID- 16288798
TI  - An anaerobic bioreactor allows the efficient degradation of HCH isomers in soil
      slurry.
AB  - The insecticide gamma-hexachlorocyclohexane (gamma-HCH or lindane), which has
      been extensively used for agricultural and medical purposes, presents high
      persistence and toxicity to the environment and low solubility. This study
      intends to assess the efficiency of an anaerobic reactor to degrade HCH isomers
      contained in soil slurry cultures. This study was developed in two phases:
      experiments in flasks to optimize the process parameters, and assessment of the
      slurry process in the anaerobic slurry reactor operated for an approximate period
      of a year. The influence of different environmental conditions was evaluated: the
      HCH concentration (25-100 mg HCH kg-1), the type of substrate (volatile fatty
      acids or starch), the sludge concentration (2-8 g VSS l-1) and the replacement of
      spiked soil to simulate a fed-batch operation (10-50%). The best results were
      obtained when the reactor was operated with a sludge concentration of 8 g VSS l
      1, starch concentration of 2 g COD l-1 and soil replacements of 10-20%. Under
      these conditions, alpha- and gamma-HCH were completely degraded after 10d while
      nearly 90% beta- and delta-HCH were removed only after 50 d. According to the
      obtained results related to the total degradation of the HCH isomers and the
      degradation rates, especially high for alpha- and gamma-HCH, the anaerobic slurry
      reactor appears to be a good alternative for the degradation of the HCH isomers
      present in polluted soil.

PMID- 16288799
TI  - Comparison of catalytic activity of two platinised TiO2 films towards the
      oxidation of organic pollutants.
AB  - Two types of platinised TiO2 films, i.e., Pt-TiO2/ITO and Pt(TiO2)/ITO, were
      prepared by a procedure of dip-coating and subsequent photo-deposition, and photo
      deposition and subsequent dip-coating, respectively. They were well characterized
      by DRS, XRD spectra, SEM microscopy and photoelectrochemical measurement. Their
      photocatalytic, dark catalytic and photoelectrocatalytic activities were
      investigated using formic acid as a model organic pollutants. Compared with pure
      TiO2/ITO film, the photocatalytic activity of the platinised TiO2 films were
      apparently improved. However, the improvement was considerably dependent on the
      preparation method of these films. Pt-TiO2/ITO not only possessed higher
      photocatalytic activity but also showed a dark catalytic activity towards HCOOH
      degradation. As a sequence, it was first emphasized that the dark catalytic
      effect of Pt-TiO2/ITO was partly responsible for degradation of formic acid in
      the photocatalytic oxidation process. Although the Pt(TiO2)/ITO film does not
      exhibit the dark catalytic activity, its photocatalytic degradation efficiencies
      towards HCOOH are higher than that of Pt-TiO2/ITO film. Therefore, in view of
      enhanced photocatalytic activity, the Pt(TiO2)/ITO was more favored than Pt
      TiO2/ITO film.

PMID- 16288800
TI  - Effects of extracellular polymeric substances on aerobic granulation in
      sequencing batch reactors.
AB  - The effects of extracellular polymeric substances on aerobic granulation in
      sequencing batch reactors were investigated by evaluating the content and
      compositions of extracellular polymeric substances, and the relationship between
      extracellular polymeric substances composition and surface properties of glucose
      fed aerobic granules. The results showed that extracellular polymeric substances
      could affect surface properties of cells, such as surface charge and
      hydrophobicity, enhance polymeric interaction and promote aerobic granulation.
      Moreover, extracellular polymeric substances were produced mainly in the
      exponential phase, and served as carbon and energy source in starvation phase
      during granulation process, thus regulating the growth of bacteria in the
      interior and exterior of granules, and maintaining the integrality of granules.

PMID- 16288801
TI  - Speciation of heavy metals during co-composting of sewage sludge with lime.
AB  - During composting the humification of organic matter will have a significant
      effect on the physicochemical form of existence of heavy metals. Therefore the
      present study was conducted to investigate the effect of co-composting sewage
      sludge with lime on heavy metal speciation and the changes in DTPA extractable
      metals. Metal speciation was conducted to evaluate the redistribution of Cu, Mn,
      Ni, Pb and Zn in sewage sludge composted with lime. Sewage sludge was mixed with
      sawdust in 2:1 (w/w fresh weight) and then composted with lime at 0%, 0.63%, 1%
      or 1.63% (dry weight) for 100 days. The lime addition did not cause any changes
      in the different forms of Cu and Mn, but the composting process caused
      transformations of residual form of Cu and Mn into oxidizable and reducible form,
      respectively. For Ni, the reducible form was mainly transformed into residual
      form and lime addition decreased this transformation. Major transformation of
      different forms of Pb was not found, however the residual form of Pb increased
      with lime addition. The predominant residual form of Zn was mainly transformed
      into oxidizable form and the lime addition reduced this transformation. Addition
      of lime to sewage sludge during composting resulted in lower DTPA extractable
      metal contents. Therefore, lime is a suitable material to co-compost with sewage
      sludge to reduce the availability of heavy metals.

PMID- 16288802
TI  - Non-electrostatic surface complexation models for protons and lead(II) sorption
      onto single minerals and their mixture.
AB  - Potentiometric titrations and lead sorption tests were conducted using muscovite,
      clinochlore, hematite, goethite, quartz, and a mixture of these same minerals.
      Mechanistic models were developed to represent and interpret these data. The aim
      was isolating the specific contribution of each mineral in proton and lead
      binding. Acid-base properties of each single mineral as well as their mixture
      were represented by discrete models, which consider the dissociation of n
      monoprotic sites (n-site/n-K(H) models). A one-site/one-K(H) model (logK(H1) =
      10.69) was chosen for quartz (dissociation of SiOH edge hydroxyl groups).
      Goethite and hematite (FeOH groups) were represented by the same one-site/one
      K(H) model (logK(H1) = 10.35). Three-site/three-K(H) models were used for
      muscovite (logK(H1) = 4.18; logK(H2) = 6.65; logK(H3) = 9.67) and clinochlore
      (logK(H1) = 3.84; logK(H2) = 6.57; logK(H3) = 9.71) assuming that SiOH and AlOH
      of the aluminosilicate matrix dissociate in the acid-neutral pH range while SiOH
      groups of quartz inclusions dissociate in the basic range. Similarly, the mixture
      of these minerals was represented by a three-site/three-K(H) model (logK(H1) =
      3.39; logK(H2) = 6.72; logK(H3) = 10.82). According to crossed comparisons with
      single minerals, the first two sites of the mixture were associated with the
      aluminosilicate matrix (SiOH and AlOH respectively) and the third site with iron
      oxides (FeOH) and quartz groups. Additivity of proton binding in the mixture was
      demonstrated by simulating the mixture's titration curve. A unified model for the
      entire set of titration curves (single minerals and mixture) was also developed
      introducing a three-peak distribution function for proton affinity constants.
      Experimental data for lead sorption onto the mixture and individual minerals in 3
      5 pH range denoted the competition between protons and metallic ions. The entire
      set of lead isotherms (individual mineral and mixture data) was represented
      adequately by a unified model taking into account both monodentate and bidentate
      complexes with the three active sites (additivity of lead binding). Experimental
      data of metal distribution in solid and liquid phases were successfully simulated
      by implementing the protonation and the surface complexation constants into the
      database of a dedicated software for chemical equilibria.

PMID- 16288803
TI  - Concurrent cisplatin/gemcitabine chemotherapy along with radiotherapy in locally
      advanced cervical carcinoma: a phase II trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of a concurrent regimen of
      gemcitabine/cisplatin and radiotherapy in women with locally advanced cervical
      carcinoma (LACC). METHODS: From April 2001 to June 2002, we enrolled women
      diagnosed with histologically proven LACC (FIGO stages IIA through IIIB), for
      treatment with concurrent regimen of chemo-radiotherapy. The treatment consisted
      of: cisplatin 40 mg/m(2), followed by gemcitabine 125 mg/m(2), once weekly, given
      about 1 to 2 h before radiotherapy. External beam radiation was delivered 5
      days/week to entire pelvic radiation field for a total of 50 Gy in 25 fractions
      over 5 weeks. After completion of external radiation, patients received
      brachytherapy with cesium-137 via standard Fletcher-suit applicators delivering
      30 Gy to point A. RESULTS: Of the 23 enrolled patients (mean age 47 years), 20
      completed the treatment and were evaluable for response and safety. The complete
      response rate was 90% (18/20), and partial response rate was 10% (2 patients with
      persistent disease after therapy). Toxicity was moderate: 2 patients required
      blood transfusions; 5% patients had grade 2 leukopenia or thrombocytopenia; 40%
      had grade 1-2 nausea-vomiting, and 50% had grade 1 diarrhea. At a median follow
      up of 12 months, all patients are alive, and 16/20 (80%) are disease-free.
      CONCLUSIONS: The gemcitabine/cisplatin combination administered concurrently with
      radiotherapy is highly active in locally advanced cervical carcinoma. The
      tolerable toxicity and synergistic activity of this concurrent chemoradiation
      regimen are consistent with prior reports. Definitive results are awaited from an
      on-going large, randomized trial comparing this regimen with standard treatment.

PMID- 16288804
TI  - New evidence for morphological errors in deep dyslexia.
AB  - Morphological errors in reading aloud (e.g., sexist-->sexy) are a central feature
      of the symptom-complex known as deep dyslexia, and have historically been viewed
      as evidence that representations at some level of the reading system are
      morphologically structured. However, it has been proposed (Funnell, 1987) that
      morphological errors in deep dyslexia are not morphological in nature but are
      actually a type of visual error that arises when a target word that cannot be
      read aloud (by virtue of its low imageability and/or frequency) is modified to
      form a visually similar word that can be read aloud (by virtue of its higher
      imageability and/or frequency). In the work reported here, the deep dyslexic
      patient DE read aloud lists of genuinely suffixed words (e.g., killer),
      pseudosuffixed words (e.g., corner), and words with non-morphological embeddings
      (e.g., cornea). Results revealed that the morphological status of a word had a
      significant influence on the production of stem errors (i.e., errors that include
      the stem or pseudostem of the target): genuinely suffixed words yielded more stem
      errors than pseudosuffixed words or words with non-morphological embeddings. This
      effect of morphological status could not be attributed to the relative levels of
      target and stem imageability and/or frequency. We argue that this pattern of data
      indicates that apparent morphological errors in deep dyslexic reading are
      genuinely morphological, and discuss the implications of these errors for
      theories of deep dyslexia.

PMID- 16288805
TI  - Impaired discourse gist and working memory in children after brain injury.
AB  - Emerging evidence suggests that a traumatic brain injury (TBI) in childhood may
      disrupt the ability to abstract the central meaning or gist-based memory from
      connected language (discourse). The current study adopts a novel approach to
      elucidate the role of immediate and working memory processes in producing a
      cohesive and coherent gist-based text in the form of a summary in children with
      mild and severe TBI as compared to typically developing children, ages 8-14 years
      at test. Both TBI groups showed decreased performance on a summary production
      task as well as retrieval of specific content from a long narrative. Working
      memory on n-back tasks was also impaired in children with severe TBI, whereas
      immediate memory performance for recall of a simple word list in both TBI groups
      was comparable to controls. Interestingly, working memory, but not simple
      immediate memory for a word list, was significantly correlated with summarization
      ability and ability to recall discourse content.

PMID- 16288806
TI  - Modified Magrath IVAC regimen as second-line therapy for relapsed or refractory
      aggressive non-Hodgkin's lymphoma in developing countries: the experience of a
      single center in Brazil.
AB  - BACKGROUND: The purpose of this retrospective study was to investigate the
      efficacy, toxicity and mobilization rate after modified Magrath IVAC (mIVAC)
      chemotherapy regimen prescribed in relapsed disease (RD) or primary refractory
      disease (PRD) in aggressive non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS:
      Twenty-four patients (16 males, 8 females) aged 18-59 years (median age 37 year)
      were analyzed. The most frequent histopathological subgroup was diffuse large B
      cell lymphoma (DLCL-B) (n=21/24), 13 (54%) were considered RD and 11 (46%) PRD.
      The mIVAC consisted of ifosfamide (IFM), high dose cytarabine and etoposide
      repeated every 28 days. RESULTS: The overall response (OR) after three cycles of
      mIVAC was 66. 6%. Among the patients with PRD, OR was 45.5% (5 out of 11) and
      with RD was 86.4%, p>0.05, however, it was observed in RD better complete
      response (CR) than PRD 53.8x9.1% (p<0.05). Eighty-eight percent (14 out of 16) of
      patients with chemosensitive disease to mIVAC underwent autologous stem cell
      transplantation (ASCT). The median number of collected CD34+ cells was 2.86x10(6)
      (range 2.17x10(6) to 4.9x10(6)). The median overall survival rate (OS) for
      chemosensitive to mIVAC was 16.3 months, with a median follow-up of 16 months.
      Grades III-IV neutropenia was observed in 85.6% per cycles and grades III-IV
      thrombocytopenia in 87.5%. Grades III-IV febrile neutropenia was the most common
      nonhematological toxicity, it occurred in 28% of the cycles and no deaths by
      toxicity were observed. DISCUSSION: Although a statistic comparative study was
      not carried out for these 24 patients, the rate of OR to mIVAC was alike the
      other second-line infusion regimens. The mobilization failure rate was 57.1% and
      it was similar to other regimens with high dose cytarabine, but it did not limit
      performed ASCT.

PMID- 16288807
TI  - Microcytosis in agnogenic myeloid metaplasia: prevalence and clinical correlates.
AB  - Microcytosis is a characteristic laboratory feature for both iron deficiency
      anemia and thalassemia. It is also infrequently seen in "anemia of chronic
      disease" that accompanies a spectrum of chronic conditions including rheumatoid
      arthritis, polymyalgia rheumatica, diabetes mellitus, connective tissue disease,
      and protracted infection. In addition, there is a well established but
      pathogenetically obscure association of microcytosis with Hodgkin's lymphoma,
      Castleman's disease, and renal cell carcinoma. In the current study, we show that
      microcytosis is a frequent laboratory feature in agnogenic myeloid metaplasia and
      investigate its clinical relevance in the particular setting.

PMID- 16288808
TI  - Recognition factors of Ricinus communis agglutinin 1 (RCA(1)).
AB  - Ricinus communis agglutinin (RCA1) is one of the most important applied lectins
      that has been widely used as a tool to study cell surfaces and to purify glycans.
      Although the carbohydrate specificity of RCA1 has been described, the information
      obtained was mainly focused on inhibition of simple Galbeta1-related
      oligosaccharides and simple clusters. Here, all possible recognition factors of
      RCA1 of glycan binding were examined by enzyme-linked lectinosorbent (ELLSA) and
      inhibition assays, using known mammalian Gal/GalNAc carbohydrate structural units
      and natural polyvalent glycans. Among the glycoproteins (gps) tested and
      expressed as 50% nanogram inhibition, the high-density polyvalent Galbeta1
      4GlcNAc (II) glycotopes occurring in natural gps, such as Pneumococcus type 14
      capsular polysaccharide which is composed of repeating poly II residues, resulted
      in 9.0 x 10(4), 1.5 x 10(5), 2.3 x 10(4) and 2.1 x 10(4)-fold higher affinities
      to RCA1 than the monomeric Gal, linear I/II and Tri-antennary-II (Tri-II). Of the
      ligands tested and expressed as nanomoles of 50% inhibition, Tri-II was the best,
      being about 2, 4, 25.6 and 33.3 times better inhibitor than Di-II, II, I
      (Galbeta1-3GlcNAc) and Gal, respectively. From the results of this study, it is
      concluded that: (a) Galbeta1-4GlcNAc and other Galbeta1-related oligosaccharides
      are essential for lectin binding and their polyvalent form in macromolecules
      should be the most important recognition factor for RCA1; (b) the combining site
      of RCA1 may be a groove type, recognizing Galbeta1-4GlcNAc (II) as the major
      binding site; (c) its combining size may be large enough to accommodate a
      tetrasaccharide of beta-anomeric Gal at the non-reducing end and most
      complementary to human blood group I Ma active trisaccharide (Galbeta1
      4GlcNAcbeta1-6Gal) and lacto-N-neotetraose (Galbeta1-4GlcNAcbeta1-3Galbeta1
      4Glc); (d) RCA1 has a preference for the beta-anomer of Gal oligosaccharides with
      a Galbeta1-4 linkage > Galbeta1-6 > or = Galbeta1-3; (e) configuration of carbon
      2, -3 -4 and -6 in Gal are essential for binding; (f) hydrophobic interaction in
      the vicinity of the binding site useful for sugar accommodation increases
      affinity. These results should be helpful for understanding the functional role
      of RCA1 and for characterizing glycotopes of mammalian complex carbohydrates.

PMID- 16288809
TI  - Mechanisms of target organ damage caused by hypertension: therapeutic potential.
AB  - Hypertension is a major risk factor for cardiovascular mortality and morbidity
      through its effects on target organs like the brain, heart, and kidney.
      Structural alterations in the microcirculation form a major link between
      hypertension and target organ damage. In this review, we describe damages related
      to hypertension in these target organs and the mechanisms involved in the
      pathogenesis of hypertension-induced cardiovascular diseases such as dementia,
      cardiac ischemia and remodeling, or nephropathy. We also focus on the
      therapeutical potential on the basis of such mechanisms. Several antihypertensive
      agents like diuretics, angiotensin converting enzyme (ACE) inhibitors,
      angiotensin II (Ang II) receptor antagonists, beta-blockers, or calcium channel
      blockers (CCBs) have been shown to reduce effectively hypertension associated
      cardiovascular events and to improve end organ damage. More recently, aldosterone
      antagonism has also shown beneficial effects. Part of the favorable effects of
      these agents is due to blood pressure lowering as such. Other mechanisms such as
      oxidative stress, inflammation, or endothelial dysfunction have appeared to play
      a key role in the pathogenesis of target organ damage and therefore represent
      another important pathway for therapy. In this review, we discuss the different
      therapeutic approaches aiming at reducing cardiovascular events and damages
      induced by hypertension.

PMID- 16288810
TI  - Sequential induction of angiogenic growth factors by TNF-alpha in choroidal
      endothelial cells.
AB  - Inflammatory mediators have been proposed to play a critical role in the
      pathogenesis of choroidal neovascularization, a blinding complication of age
      related macular degeneration. We evaluated the expression of TNF-alpha in human
      choroidal neovascular membranes and found that it colocalized with cells
      expressing VEGF, angiopoietin (Ang)-1 and Ang2. In cultured choroidal endothelial
      cells we found that TNF-alpha increased Ang2 mRNA (increased transcription) and
      protein levels prior to those of Ang1 and VEGF. The results raise the possibility
      that during neovascularization, TNF-alpha may modulate endothelial plasticity and
      survival by sequential inactivation of Tie2 followed by activation of Tie2 and
      VEGF receptors.

PMID- 16288811
TI  - Autonomic correlates of social anxiety and embarrassment in shy and non-shy
      individuals.
AB  - Social anxiety and embarrassment are closely related constructs, both of which
      are relevant to the study of shyness. To examine the psychophysiological
      correlates of anxiety and embarrassment in relation to shyness, we measured
      autonomic arousal (heart rate, respiratory sinus arrhythmia, skin conductance
      level, and blushing response) in shy and non-shy female participants while they
      performed tasks designed to elicit either social anxiety or embarrassment.
      Results indicated that social anxiety and embarrassment are difficult to
      disentangle at the autonomic level. Blushing may be an important
      psychophysiological marker of shyness and social anxiety.

PMID- 16288812
TI  - Performance monitoring in neurological and psychiatric patients.
AB  - Performance monitoring, an indispensable prerequisite of goal-directed, flexible
      behavior has attracted the interest of many researchers. Performance monitoring
      impairment may result in major daily-life problems in neurological and
      psychiatric patients. In this paper, I review the recent advances in clinical
      studies on performance monitoring in different populations of neurological and
      psychiatric patients. The findings are discussed with respect to current models
      of performance monitoring that have mostly arisen from correlational approaches.
      Moreover, perspectives for clinical use are given and methodological issues for
      patient studies of performance monitoring will be discussed.

PMID- 16288813
TI  - Streptococcus macedonicus ACA-DC 198 produces the lantibiotic, macedocin, at
      temperature and pH conditions that prevail during cheese manufacture.
AB  - Streptococcus macedonicus ACA-DC 198, a natural cheese isolate, produces the
      anticlostridial bacteriocin, macedocin. Bacteriocin activity was detected from
      the mid-exponential growth phase and remained constant during the stationary
      phase. A secondary model was setup to describe the influence of temperature (20
      45 degrees C) and pH (5.1-6.9) on cell growth of and bacteriocin production by S.
      macedonicus ACA-DC 198 during in vitro laboratory fermentations. The optimum
      temperature for bacteriocin production (20-25 degrees C) was markedly lower than
      the optimum growth temperature (42.3 degrees C). In contrast, the specific
      macedocin production was maximal around pH 6.0, whereas growth was optimal at pH
      6.4. Consequently, the maximum bacteriocin activity was reached between pH 6.0
      and 6.5.

PMID- 16288814
TI  - A multi-scale stochastic drug release model for polymer-coated targeted drug
      delivery systems.
AB  - A multi-scale mathematical model for drug release of oral targeted drug delivery
      systems was developed and applied to a commercially available delayed release
      tablet (Asacol) that delivers 5-aminosalicyclic acid (5-ASA) to the colon.
      Underlying physical and biochemical principles governing the involved processes
      (diffusion and dissolution) were employed to develop the mathematical
      description. Finite element formulation was used to numerically solve the model
      equations. Molecular dynamics (MD) simulations were used to predict macro-scale
      transport properties of the drug and the biologic fluid. The effect of pH
      variability in the gastrointestinal tract environment on the dissolution of the
      polymeric enteric coating was investigated using the Monte Carlo method. The
      direct coupling method employed (MD) predicted a sufficiently accurate diffusion
      coefficient (5.7x10(-6) cm2 s-1) of the drug molecules in reasonable (3 h)
      computation times. The model was validated using experimental data from in vitro
      dissolution experiments and provided accurate prediction of the drug release from
      the delivery system (root mean square error of 5%). The amount of drug entering
      the systemic circulation, computed from the predicted drug release in varying pH
      environments in the small bowel, was 15-24%. This range was in good agreement
      with clinical in vivo data (13-36%) obtained from literature. This research shows
      that in silico experiments using mechanistic models and stochastic approaches can
      be used for drug design and optimization and as a decision making tool for
      physicians.

PMID- 16288815
TI  - The role of polymer membrane formation in sustained release drug delivery
      systems.
AB  - A discussion of the role of polymer membrane-based drug delivery systems is
      presented. This is followed with a review of recent studies in our laboratories
      of the membrane formation and drug delivery characteristics of injectable polymer
      solution platforms. Attention is focused on the role of depot formulation in
      terms of solvent quality and water miscibility and polymer type (amorphous versus
      crystallizable), as well as the effects of bath-side additives on the in vitro
      release behavior. A quantitative model describing the protein release dynamics in
      fast phase inverting systems (FPI) is also discussed.

PMID- 16288816
TI  - Sleep and body weight in diabetes mellitus: a large retrospective analysis from
      South India.
AB  - AIM: To analyze the pattern of sleep disorders among 4624 individuals with type 2
      diabetes mellitus who complained of disturbed sleep at our centre in South India.
      METHODS: Retrospective analysis of data from electronic medical records. RESULTS:
      Body mass index or body weight was not related to the prevalence of sleep
      disturbances. They were more in sedentary individuals, who consumed alcoholic
      beverages, and those with known hypertension or with a family history of
      diabetes. Body mass index was not a risk factor even after excluding known
      factors disturbing sleep (viz. nocturia, body pains, burning soles). CONCLUSION:
      Body weight in type 2 diabetes mellitus was not related to the prevalence of
      sleep disorders in our sample.

PMID- 16288817
TI  - Prevalence and predictors of microalbuminuria in patients with type 2 diabetes
      mellitus: a cross-sectional observational study in Oman.
AB  - AIM: To evaluate the prevalence and predictors of microalbuminuria in type 2
      diabetics in Oman. METHODS: All patients attending an outpatient diabetic clinic
      at the Sultan Qaboos University Hospital between 2002 and 2003 were enrolled in
      the study. RESULTS: A total of 261 patients were included in this study. The mean
      overall age of the cohort was 50+/-13 years, and 57% were male. The proportion of
      subjects who had microalbuminuria was 27% (n=70; N=261). The logistic regression
      model indicated that significant predictors for the development of
      microalbuminuria include HbA(1c), log creatinine, and the presence of
      hypertension. A one unit increase in HbA(1c) was associated with a 23% increase
      in the odds of developing microalbuminuria (OR 1.23; 95% CI: 1.10-1.37; p<0.001).
      Additionally, patients that had a one unit increase in log creatinine were 5.72
      times more likely to develop microalbuminuria (OR 5.72; 95% CI: 1.86-17.59;
      p=0.002). Furthermore, patients who were hypertensive were 2.37 times more likely
      to have microalbuminuria (OR 2.37; 95% CI: 1.11-5.09; p=0.026). CONCLUSIONS: The
      prevalence of microalbuminuria in patients with type 2 diabetes in this study was
      27%. Significant predictors of microalbuminuria included HbA(1c), creatinine, and
      the presence of hypertension.

PMID- 16288818
TI  - The ROC analysis for different time points during oral glucose tolerance test.
AB  - This purpose was to discuss optimal reference value for normal glucose tolerance
      (NGT) at different time points during an oral glucose tolerance test (OGTT) by
      receiver operating characteristic (ROC) analysis. One thousand seven hundred and
      forty-six subjects from March 2004 to March 2005 were given 75 g OGTT and the
      blood samples were collected at 0, 30, 60, 120 and 180 min for glucose
      measurement. Other demographic data (e.g. age, sex, body mass index, BMI) were
      also recorded. The status of NGT, impaired glucose tolerance (IGT), impaired
      fasting glucose (IFG) and DM was determined according to American Diabetes
      Association (ADA) criteria. IGT and IFG were merged as impaired glucose
      regulation (IGR). Using IGR as the assumed test, the cutoff values at 0, 30, 60,
      120 and 180 min during OGTT for normal reference range were calculated by ROC
      analysis. The cutoff values were 5.6, 9.5, 10.1, 7.8 and 6.1 mmol/l at 0, 30, 60,
      120 and 180 min, respectively, in whole subjects. In addition, we provided the
      ROC information in age-stratified groups since there are differences among
      different age groups. When the results of OGTT were considered, the present study
      provided a reference range value to evaluate the status of glucose tolerance.
      Because of the heterogeneity of diabetes, further studies are necessity. And the
      sample collection is continuing.

PMID- 16288819
TI  - Successful treatment of severe unconjugated hyperbilirubinemia via induction of
      UGT1A1 by rifampicin.
AB  - We report two patients with uncommon Gilbert's syndrome with severe unconjugated
      hyperbilirubinemia which was reduced from 200 to 60-90 micromol/L by long-term
      administration of rifampicin. Hepatic induction of bilirubin
      glucuronosyltransferase was suggested by increased relative amounts of conjugated
      serum bilirubin. This molecular mechanism was confirmed in primary cultures of
      human hepatocytes.

PMID- 16288820
TI  - Effect of immunization with herpes simplex virus type-1 (HSV-1) glycoprotein D
      (gD) plus the immune enhancer GPI-0100 on infection with HSV-1 or HSV-2.
AB  - These studies were performed to determine the effects of GPI-0100, a semi
      synthetic Quillaja Saponin analog, formulated with herpes simplex virus type-1
      (HSV-1) glycoprotein D (gD) on immunity to HSV. SKH-1 hairless mice, used as a
      model of herpes labialis, inoculated with HSV-1 results in facial lesions, virus
      replication and mortality. Mortality rates, lesion scores and viral titers were
      significantly reduced in SKH-1 mice immunized with gD/GPI-0100 prior to cutaneous
      inoculation with HSV-1 and the protective effects were greater than those using
      the standard alum adjuvant. Genital HSV-2 infections in guinea pigs were also
      utilized to determine if gD combined with GPI-0100 was protective against
      infection, disease severity and viral shedding. Guinea pigs immunized with HSV-1
      gD with or without GPI-0100 had significantly reduced area under the curve lesion
      scores, but infection rates and virus shedding was not altered. When Tween 40 was
      added to gD and GPI-0100, mean peak lesion scores were also significantly
      reduced. The results obtained in a genital HSV-2 infection of guinea pigs did not
      indicate enhanced protection or reduced virus shedding following immunization
      with GPI-0100 and gD. There was, however, a significant improvement in clinical
      herpetic genital disease with the combination of gD plus the immune enhancer GPI
      0100.

PMID- 16288821
TI  - Encapsulation of proteins and peptides into biodegradable poly(D,L-lactide-co
      glycolide) microspheres prolongs and enhances antigen presentation by human
      dendritic cells.
AB  - Dendritic cell (DC)-based immunotherapy has been hampered by the lack of suitable
      methods for antigen delivery. Here, we use biodegradable poly(D,L-lactide-co
      glycolide) microspheres (PLGA-MS) as carriers of peptides and proteins for
      antigen delivery to human monocyte-derived DC (MoDC). Compared to soluble
      proteins, MHC classes I and II-restricted presentation of PLGA-MS-encapsulated
      proteins and peptides by MoDC was markedly prolonged and proteins were presented
      50-fold more efficiently on class I molecules. The vaccination of mice with DC
      loaded with PLGA-MS-encapsulated proteins raised strong and persisting cytotoxic
      T cell responses. In conclusion, antigen delivery via PLGA-MS markedly enhanced
      the duration of antigen presentation by human MoDC and the potency of DC-based
      vaccination.

PMID- 16288822
TI  - A dose sparing effect by plasmid encoded IL-12 adjuvant on a SIVgag-plasmid DNA
      vaccine in rhesus macaques.
AB  - An experimental pDNA vaccine adjuvant expressing IL-12 was evaluated for its
      ability to augment the humoral and cellular immune responses elicited by a
      SIVmac239 gag p39 expressing pDNA vaccine. To determine the effect of vaccine
      dose on the immune response, rhesus macaques were immunized with 1.5 mg or 5.0 mg
      of SIVmac239 gag pDNA, with or without co-immunization of IL-12 pDNA at 1.5 mg
      and 5.0 mg, respectively. Serum antibody responses to simian immunodeficiency
      virus (SIV) gag were increased 10-fold (p=0.044, 0.002) in macaques receiving IL
      12 pDNA. Cellular immune responses, monitored by SIV gag-specific IFN-gamma
      ELISpot assay, were also significantly higher (p=0.007, 0.019) when the pDNA
      vaccine was co-immunized with IL-12 pDNA at high and low doses. There was no
      statistical difference between the immune responses elicited by the high and low
      dose of IL-12 pDNA (p=0.221, 0.917), a finding which could allow a dose reduction
      of vaccine without the concomitant loss of imunogenicity. Furthermore, analysis
      of the breadth of the T-cell response during the vaccination schedule, using
      overlapping peptides to SIV gag, demonstrated a significant correlation
      (p=0.0002) between the magnitude and breadth of the immune responses in the
      vaccines. These results have important implications for the continuing
      development of an effective, safe low dose pDNA vaccine adjuvant suitable for
      human use.

PMID- 16288823
TI  - Which factors affect hand selection in children's grasping in hemispace? Combined
      effects of task demand and motor dominance.
AB  - Sixty-five right- and left-handed preschool and school children were tested on
      three reach-to-grasp tasks of different levels of complexity, performed in three
      space locations. Our goal was to evaluate how the effect of attentional
      information related to object location interacts with task complexity and degree
      of handedness on children's hand selection. Results revealed a shift to the non
      preferred hand in the contralateral hemispace, which was more or less pronounced
      according to the level of task complexity. The subject's degree of handedness
      also influenced this shift, since strongly lateralized children exhibited a
      greater use of their preferred hand than less lateralized ones for actions in the
      contralateral hemispace. These findings confirm that hand selection is to some
      extent adaptable to task demand and environmental context.

PMID- 16288824
TI  - Integrative modelling for sustainable water allocation: editorial notes on the
      special issue.

PMID- 16288825
TI  - Computer software tool REALM for sustainable water allocation and management.
AB  - REALM (REsource ALlocation Model) is a generalised computer simulation package
      that models harvesting and bulk distribution of water resources within a water
      supply system. It is a modeling tool, which can be applied to develop specific
      water allocation models. Like other water resource simulation software tools,
      REALM uses mass-balance accounting at nodes, while the movement of water within
      carriers is subject to capacity constraints. It uses a fast network linear
      programming algorithm to optimise the water allocation within the network during
      each simulation time step, in accordance with user-defined operating rules. This
      paper describes the main features of REALM and provides potential users with an
      appreciation of its capabilities. In particular, it describes two case studies
      covering major urban and rural water supply systems. These case studies
      illustrate REALM's capabilities in the use of stochastically generated data in
      water supply planning and management, modelling of environmental flows, and
      assessing security of supply issues.

PMID- 16288826
TI  - A decision support for an integrated multi-scale analysis of irrigation: DSIRR.
AB  - The paper presents a decision support designed to conduct an economic
      environmental assessment of the agricultural activity focusing on irrigation
      called 'Decision Support for IRRigated Agriculture' (DSIRR). The program
      describes the effect at catchment scale of choices taken at micro scale by
      independent actors, the farmers, by simulating their decision process. The
      decision support (DS) has been thought of as a support tool for participatory
      water policies as requested by the Water Framework Directive and it aims at
      analyzing alternatives in production and technology, according to different
      market, policy and climate conditions. The tool uses data and models, provides a
      graphical user interface and can incorporate the decision makers' own insights.
      Heterogeneity in preferences is admitted since it is assumed that irrigators try
      to optimize personal multi-attribute utility functions, subject to a set of
      constraints. Consideration of agronomic and engineering aspects allows an
      accurate description of irrigation. Mathematical programming techniques are
      applied to find solutions. The program has been applied in the river Po basin
      (northern Italy) to analyze the impact of a pricing policy in a context of
      irrigation technology innovation. Water demand functions and elasticity to water
      price have been estimated. Results demonstrate how different areas and systems
      react to the same policy in quite a different way. While in the annual cropping
      system pricing seems effective to save the resource at the cost of impeding Water
      Agencies cost recovery, the same policy has an opposite effect in the perennial
      fruit system which shows an inelastic response to water price. The
      multidimensional assessment conducted clarified the trades-off among conflicting
      economic-social-environmental objectives, thus generating valuable information to
      design a more tailored mix of measures.

PMID- 16288827
TI  - A multi-objective optimisation approach to water management.
AB  - The management of river basins is complex especially when decisions about
      environmental flows are considered in addition to those concerning urban and
      agricultural water demand. The solution to these complex decision problems
      requires the use of mathematical techniques that are formulated to take into
      account conflicting objectives. Many optimization models exist for water
      management systems but there is a knowledge gap in linking bio-economic
      objectives with the optimum use of all water resources under conflicting demands.
      The efficient operation and management of a network of nodes comprising storages,
      canals, river reaches and irrigation districts under environmental flow
      constraints is challenging. Minimization of risks associated with agricultural
      production requires accounting for uncertainty involved with climate,
      environmental policy and markets. Markets and economic criteria determine what
      crops farmers would like to grow with subsequent effect on water resources and
      the environment. Due to conflicts between multiple goal requirements and the
      competing water demands of different sectors, a multi-criteria decision-making
      (MCDM) framework was developed to analyze production targets under physical,
      biological, economic and environmental constraints. This approach is described by
      analyzing the conflicts that may arise between profitability, variable costs of
      production and pumping of groundwater for a hypothetical irrigation area.

PMID- 16288828
TI  - A comparative analysis of predictors of sense of place dimensions: attachment to,
      dependence on, and identification with lakeshore properties.
AB  - Sense of place can be conceived as a multidimensional construct representing
      beliefs, emotions and behavioural commitments concerning a particular geographic
      setting. This view, grounded in attitude theory, can better reveal complex
      relationships between the experience of a place and attributes of that place than
      approaches that do not differentiate cognitive, affective and conative domains.
      Shoreline property owners (N=290) in northern Wisconsin were surveyed about their
      sense of place for their lakeshore properties. A predictive model comprising
      owners' age, length of ownership, participation in recreational activities, days
      spent on the property, extent of property development, and perceptions of
      environmental features, was employed to explain the variation in dimensions of
      sense of place. In general, the results supported a multidimensional approach to
      sense of place in a context where there were moderate to high correlations among
      the three place dimensions. Perceptions of environmental features were the
      biggest predictors of place dimensions, with owners' perceptions of lake
      importance varying in explanatory power across place dimensions.

PMID- 16288829
TI  - Dose-dependent benzo(a)pyrene [B(a)P]-DNA adduct levels and persistence in F-344
      rats following subchronic dietary exposure to B(a)P.
AB  - In order to investigate the relationship between BaP-DNA adduct formation and
      long-term exposure to benzo(a)pyrene (BaP), DNA adduct levels in liver and lung
      tissues of male and female F-344 rats subchronically exposed to BaP were
      determined. Doses of 0, 5, 50, and 100mg/kg BaP, representing control, low,
      intermediate, and high doses, respectively, were administered in the animal diet
      over a 90-day period. After dosing, animals were sacrificed, liver and lung
      tissues were removed, DNA was isolated and analyzed for BaP-induced DNA adducts
      by the (32)P-postlabeling method using a four-directional thin-layer
      chromatography system. At low and intermediate BaP doses, DNA adduct levels in
      the tissues were significantly correlated with exposure. However, at high BaP
      doses, the dose-DNA adduct relationship became non-linear. Similarly, the
      relative DNA adducts persistence at intermediate and high doses were
      significantly higher than that measured at low dose. The low and intermediate
      dose linearity and high dose non-linearity may be due to saturation of metabolic
      activation and detoxification enzymes, and DNA repair processes.

PMID- 16288830
TI  - Polymorphisms in the MDM2 promoter and risk of breast cancer: a case-control
      analysis in a Chinese population.
AB  - MDM2 is a phosphoprotein that interacts with P53 and inhibits its activity.
      Recently, a T/G substitution (SNP309) in the promoter of MDM2 was identified and
      has been demonstrated to be associated with an increased MDM2 expression and a
      significantly earlier age of onset of several tumors, including breast cancer. To
      test the hypothesis that this functional variant in the MDM2 promoter is
      associated with risk of breast cancer, we conducted a molecular epidemiological
      study of 366 breast cancer cases (BC), 263 patients with benign breast diseases
      (BBD) and 605 cancer-free controls in China, in which we genotyped this T/G
      variant and another common insertion/deletion polymorphism (Del1518) in the MDM2
      promoter and evaluated the associations between these two polymorphisms and
      breast cancer risk. We found that the variant allele frequencies of these two
      polymorphisms were not statistically different between the cases and controls
      (SNP309G: 0.500, 0.542, and 0.506 in BC, BBD, and controls, respectively, and
      Del1518-: 0.296, 0.308, and 0.297 in BC, BBD, and controls, respectively).
      Logistic regression analyses revealed that the variant genotypes of both MDM2
      SNP309 and Del1518 polymorphisms were not significantly associated with risk of
      breast cancer (adjusted OR, 1.03; 95% CI, 0.74-1.42 for SNP309 TG and GG; and
      adjusted OR, 1.09; 95% CI, 0.83-1.43 for Del1518 +/- and -/-). These findings
      suggest that these two MDM2 promoter variants may not play a major role in the
      etiology of breast cancer.

PMID- 16288831
TI  - Manifestation, mechanisms and mysteries of gene amplifications.
AB  - Gene amplifications are essential features of advanced cancers and have
      prognostic as well as therapeutic significance in clinical cancer treatment.
      Models explaining the amplification process, such as breakage-fusion-bridge cycle
      and excision and unequal segregation of extrachromosomal DNA fragments, predict
      that independent DNA double-stranded breaks must occur to induce amplification
      formation. Many cellular, tissue and environmental factors induce DNA damage and
      amplifications. Also labile DNA sequence features like fragile sites facilitate
      amplifications. Although, databases and data mining tools of various genomic
      attributes are already available, extra-large scale systems biology endeavors to
      decipher dynamics, interactions and dependencies between different factors
      contributing to amplification process fail, because current databases of DNA copy
      number aberrations and fragile sites comprise conventional cytogenetics results
      obtained at far too coarse chromosome band resolution. Array comparative genomic
      hybridization (aCGH) enables genome-wide gene copy number measurements and
      amplification detection at molecular genetic resolution. Similarly, cloning and
      sequencing of fragile sites produce mapping information of vastly improved
      resolution. In conclusion, databases of aCGH and sequenced fragile sites are
      needed to resolve the mechanisms of gene amplifications in systems biology
      configuration.

PMID- 16288832
TI  - Incidence and age distribution of colorectal cancer in Iran: results of a
      population-based cancer registry.
AB  - Epidemiologic patterns of colorectal cancer (CRC) in Iran have not been studied
      adequately. In a recent cancer registry and active cancer surveillance, we
      collected data on the incidence of colorectal tumors in five provinces of Iran
      from 1996 to 2000. In total, 2055 were registered in this study. Age-adjusted
      rates of CRC in Iranian males and females were 8.2 and 7.0/100,000, respectively.
      Seventeen percent of the cases were younger than 40 years of age at the time of
      diagnosis. This proportion was similar to proportions seen in many other Middle
      Eastern countries, but much higher than those seen in Western countries. A
      comparison of age-specific rates between Iran and the US showed similar rates in
      young (<40 years) Iranians and Americans, but much lower rates in older (>/=40)
      Iranians. We conclude that Iran is still a country with low-risk of CRC,
      particularly for older individuals. The high proportions of young CRC cases seen
      in Iran, and probably many neighboring countries, are due to the young age
      structure of these countries and relatively low rates of CRC in older
      individuals.

PMID- 16288834
TI  - Is slow coronary flow associated with inflammation?
AB  - Cardiologists are familiar with the phenomenon of slow progression of
      angiographic contrast in the coronary arteries in the absence of stenosis in the
      epicardial vessels in some patients presenting with chest pain. This phenomenon
      is called as coronary slow flow phenomenon, and firstly described in 1972, while
      it remains scantily studied. The pathophysiological mechanisms of coronary slow
      flow phenomenon remain uncertain. Several hypotheses however, have been suggested
      for slow coronary flow phenomenon, including a form of early phase of
      atherosclerosis, small vessel dysfunction, Hagen-Poiseuille's equation model,
      imbalance between vasoconstrictor and vasodilatory factors, and platelet function
      disorder. More recently, there has been mounting evidence that inflammation plays
      an important role in the initiation, development as well as evolution of
      atherosclerosis, suggesting that atherosclerosis is an inflammation disease. New
      evidence has also indicated that inflammation may be involved in the development
      of slow coronary flow phenomenon. Coronary slow flow phenomenon is an important
      clinical entity because it may be the cause of angina at rest or during exercise,
      acute myocardial infarction, and hypertension. Despite the good prognosis of this
      kind of patients, the chronic, frequent nature of the persistent uncomfortable
      chest can significantly impair the quality of life. Whether this is really a new
      kind of coronary disease involving in inflammation, however, is still unknown and
      deserves further investigation.

PMID- 16288833
TI  - Alternative estrogen receptors homologous to classical receptor alpha in murine
      neural tissues.
AB  - Although it is widely accepted the existence of putative estrogen receptors (ERs)
      localized at extranuclear domains in the brain, their molecular identity is still
      unclear. We have previously demonstrated in a murine septal cell line the
      existence of a membrane-related ER (mER) that participates in estrogen-mediated
      neuroprotection. To investigate the molecular structure of mER, we have used a
      battery of antibodies raised against different domains of the classical ERalpha
      to immunoblot with plasma membrane fractions from septal SN56 and hippocampal
      HT22 cell lines, and microsomal fractions of mouse septal and hippocampal
      tissues. The results confirmed that mER is the homologue of its intracellular
      counterpart ERalpha, suggesting the possibility that both nuclear and
      extranuclear receptors may share a common origin.

PMID- 16288835
TI  - Coaggregation ability of Weissella cibaria isolates with Fusobacterium nucleatum
      and their adhesiveness to epithelial cells.
AB  - In the present study, we evaluated the ability of Weissella cibaria isolated from
      the oral cavity to coaggregate with Fusobacterium nucleatum, and the adhesiveness
      of these strains to epithelial cells. W. cibaria efficiently coaggregated with F.
      nucleatum, and adhered to epithelial cells. We tested the effects of various
      factors on the coaggregation. The coaggregation and adhesiveness of W. cibaria
      disappeared upon exposure to pronase or LiCl, suggesting that proteinaceous
      components on the surface of W. cibaria mediated the coaggregation and
      adhesiveness. In conclusion, W. cibaria may serve as a potential probiotic with
      the ability to establish an oral flora protecting against oral pathogens.

PMID- 16288836
TI  - Osmotic shock: a mechanosensitive channel blocker can prevent release of
      cytoplasmic but not periplasmic proteins.
AB  - When over-expressed in the cytoplasm of Escherichia coli, carboxylesterase Est55
      of Geobacillus stearothermophilus was found to be released from cells upon
      osmotic shock. Comparing two osmotic shock protocols showed that release of Est55
      was abolished in the absence of mechanosensitive channel MscL by one method but
      not the other. The discrepancy extended to several previously reported
      cytoplasmic proteins released by osmotic shock, including: EF-Tu, thioredoxin,
      and DnaK in E. coli. Stepwise analyses of parameters between these two protocols
      revealed that the use of mechanical pipetting instead of gentle dilution of cells
      prior to exposure to hypotonic solution abolished the effect of MscL.
      Furthermore, while this phenomenon of release of certain cytoplasmic proteins was
      sustained in all three wild type strains of E. coli, presence of gadolinium was
      able to serve as an MscL channel blocker and prevented release of Est55 and EF-Tu
      in the process. An optimized protocol of osmotic shock was developed from this
      study to provide a more reliable assessment of location of proteins in E. coli.
      This method allowed release of authentic periplasmic MalE and beta-lactamase
      proteins comparable to that by EDTA-lysozyme treatment.

PMID- 16288837
TI  - Evaluation of phenolics and sugars as inducers of quercetinase activity in
      Penicillium olsonii.
AB  - Quercetinase is produced by various filamentous fungi when grown on rutin as sole
      carbon and energy source. We investigated on the effect of 10 phenolics and two
      sugars, structurally related to substrates and products of the rutin catabolic
      pathway, on the induction of a quercetinase activity in Penicillium olsonii.
      Neither the sugars (glucose and rhamnose, two constituents of rutin), nor
      phenolics such as protocatechuic acid, salicylic acid, 4-hydroxy-benzoic acid and
      phloroglucinol were inducers. Rutin (maximum activity 150 nmol/min/mL after 5
      days), quercetin (70 nmol/min/mL, 3 days), phloroglucinol carboxylic acid (60
      nmol/min/mL, 3 days), 2-protocatechuoylphloroglucinolcarboxylic acid (50
      nmol/min/mL, 5 days), 2,6-dihydroxy-carboxylic acid (90 nmol/min/mL, 7 days) and
      2,4-dihydroxy-carboxylic acid (30 nmol/min/mL, 7 days) were demonstrated to be
      quercetinase inducers. We propose that rutin, quercetin and 2-protocatechuoyl
      phloroglucinol carboxylic acid, the product of the reaction catalysed by
      quercetinase, act as inducers after their catabolic transformation in
      phloroglucinol carboxylic acid.

PMID- 16288838
TI  - Models of spliceosomal intron proliferation in the face of widespread ectopic
      expression.
AB  - It is now certain that today living organisms can acquire new spliceosomal
      introns in their genes. The proposed sources of spliceosomal introns are exons,
      transposons, and other introns, including spliceosomal and group II self-splicing
      introns. Spliceosomal introns are thought to be the most likely source, because
      the inserted sequence would immediately be endowed with the essential set of
      intron recognition sequences, thereby preventing the deleterious effects
      associated with incorrect splicing. The most obvious spliceosomal intron
      duplication pathways involve an RNA transcript intermediate step. Therefore, for
      a spliceosomal intron to be originated by duplication, either the source gene
      from which the novel intron is derived, or that gene and the recipient gene,
      which contains the novel intron, would need to be expressed in the germ line.
      Intron proliferation surveys indicate that putative intron duplicate-containing
      genes do not always match detectable expression in the germ line, which casts
      doubt on the generality of the duplication model. However, judging mechanisms of
      intron gain (or loss) from present-day gene expression profiles could be
      erroneous, if expression patterns were different at the time the introns arose.
      In fact, this may likely be so in most cases. Ectopic expression, i.e., the
      expression of genes at times and locations where the target gene is not known to
      have a function, is a much more common phenomenon than previously realized. We
      conclude with a speculation on a possible interplay between spliceosomal introns
      and ectopic expression at the origin of multicellularity.

PMID- 16288839
TI  - Transcription of two human genes from a bidirectional endogenous retrovirus
      promoter.
AB  - Eight percent of the human genome is derived from endogenous retrovirus (ERV)
      insertions. ERV long terminal repeats (LTRs) contain strong promoters that are
      known to contribute to the transcriptional regulation of certain human genes.
      While some LTRs are known to possess bidirectional promoter activity in vitro,
      only sense orientation LTR promoters have previously been shown to regulate human
      gene expression. Here we demonstrate that an ERV1 LTR acts as a bidirectional
      promoter for the human Down syndrome critical region 4 (DSCR4) and DSCR8 genes.
      We show that while DSCR4 and DSCR8 are essentially co-expressed, their shared LTR
      promoter is more active in the sense than the antisense orientation. Through
      deletion analysis of the LTR we have identified positive and negative regulatory
      elements, and defined a core region of the promoter that is required for
      transcriptional activity in both orientations. Finally, we show that the ERV LTR
      also exists in the genomes of several non-human primates, and present evidence
      that potential transcription factor binding sites in the core region have been
      maintained throughout primate evolution.

PMID- 16288840
TI  - A CIDR-based timed AI protocol can be effectively used for dairy cows with
      follicular cysts.
AB  - The present study evaluated whether a controlled internal drug release (CIDR)
      based timed AI (TAI) protocol could be used as an efficient tool for the
      treatment of ovarian follicular cysts in lactating dairy cows. In the first
      experiment, lactating dairy cows diagnosed with follicular cysts were randomly
      assigned to two treatments: (1) a single injection of GnRH at diagnosis (Day 0)
      and AI at estrus (AIE) within 21 days (GnRH group, n=70), or (2) insertion of a
      CIDR device containing progesterone and an injection of GnRH on Day 0,
      PGF(2alpha) injection at the time of CIDR removal on Day 7, GnRH injection on Day
      9, and TAI 16h after the GnRH injection (CIDR-based TAI group, n=65). Conception
      rate after the CIDR-based TAI protocol (52.3%) was greater (P<0.05) than that
      after AIE following a single GnRH injection (26.9%). In the second experiment,
      lactating dairy cows diagnosed with follicular cysts (Cyst group, n=16) and cows
      having normal estrous cycles (CYC group, n=15) received the same treatment: a
      CIDR device containing progesterone and an injection of GnRH on Day 0,
      PGF(2alpha) injection at the time of CIDR removal on Day 7, and GnRH injection on
      Day 9. The proportion of cows with follicular wave emergence and the interval
      from treatment to follicular wave emergence did not differ (P>0.05) between
      groups. The mean diameters of dominant follicles on Days 4 and 7 as well as
      preovulatory follicles on Day 9, and the synchrony of ovulation following the
      second injection of GnRH did not differ (P>0.05) between groups. These data
      suggest that the CIDR-based TAI protocol results in an acceptable conception rate
      in dairy cows with follicular cysts.

PMID- 16288841
TI  - Quantification of low levels of amorphous content in sucrose by hyperDSC.
AB  - A method was developed for the quantification of low levels of amorphous content
      in sucrose with hyperDSC. The method was based on the fact that the change of
      specific heat at the glass transition is linearly proportional to the amorphous
      content. It was found out that as annealing time increased, the glass transition
      temperature moved to a higher temperature and the change of specific heat
      increased. DeltaC(p) for annealed totally amorphous sucrose was 0.761+/-0.012 Jg(
      1) degrees C(-1). Synthetic mixtures with various proportions of crystalline and
      amorphous sucrose were prepared. The following linear regression between
      DeltaC(p) and amorphous content was obtained: DeltaC(p)=0.0075x - 0.00484
      (R=0.999). The limit of detection (LOD) and the limit of quantification (LOQ)
      values were 0.062 and 0.207%, respectively. The effect of grinding time on the
      amorphous content of crystalline sucrose was studied and a correlation between
      grinding time and amorphous content of sucrose was found. It was also found that
      the amorphous content could only attain a value of about 80-90% by grinding in
      the way used in this study.

PMID- 16288842
TI  - Sorption of unoprostone isopropyl to packaging materials.
AB  - This study investigated the stability of an ophthalmic solution formulation of
      unoprostone isopropyl (UI), a prostaglandin like compound, in two types of
      packaging materials, polypropylene (PP) and low-density polyethylene (LDPE). We
      determined the concentration of UI and its degradation products as a function of
      time and found that the rate of disappearance of drug was faster for the
      formulation stored in LDPE bottles than that stored in PP bottles. Further
      studies indicated that the inferior stability observed with the LDPE packaging
      was primarily due to the sorption of UI to the packaging material and to a lesser
      degree, chemical degradation. The sorption was temperature dependent, lowering
      the temperature reduced the sorption, thus improving the shelf-life of the
      product.

PMID- 16288843
TI  - Heart embolization with the Kirschner wire without cardiac tamponade.
AB  - The case of the heart embolization with the Kirschner wire that was used for
      shoulder trauma fixation, 2 years previously in a 67-year-old female, is
      reported. This case is unique; although embolization of foreign bodies to the
      heart is not a novel occurrence, heart embolization with non-broken Kirschner
      wire with a total length of 13.5 cm without cardiac tamponade was not described
      in medical literature so far.

PMID- 16288844
TI  - Understanding Candida rugosa lipases: an overview.
AB  - Candida rugosa lipase (CRL) is one of the enzymes most frequently used in
      biotransformations. However, there are some irreproducibility problems inherent
      to this biocatalyst, attributed either to differences in lipase loading and
      isoenzymatic profile or to other medium-engineering effects (temperature, a(w),
      choice of solvent, etc.). In addition, some other properties (influence of
      substrate and reaction conditions on the lid movement, differences in the
      glycosylation degree, post-translational modifications) should not be ruled out.
      In the present paper the recent developments published in the CRL field are
      overviewed, focusing on: (a) comparison of structural and biochemical data among
      isoenzymes (Lip1-Lip5), and their influence in the biocatalytical performance;
      (b) developments in fermentation technology to achieve new crude C. rugosa
      lipases; (c) biocatalytical reactivity of each isoenzyme, and methods for
      characterising them in crude CRL; (d) state-of-the-art of new applications
      performed with recombinant CRLs, both in CRL-second generation (wild-type
      recombinant enzymes), as well as in CRL-third generation, (mutants of the wt
      CRL).

PMID- 16288845
TI  - Genomics, metagenomics and proteomics in biomining microorganisms.
AB  - The use of acidophilic, chemolithotrophic microorganisms capable of oxidizing
      iron and sulfur in industrial processes to recover metals from minerals
      containing copper, gold and uranium is a well established biotechnology with
      distinctive advantages over traditional mining. A consortium of different
      microorganisms participates in the oxidative reactions resulting in the
      extraction of dissolved metal values from ores. Considerable effort has been
      spent in the last years to understand the biochemistry of iron and sulfur
      compounds oxidation, bacteria-mineral interactions (chemotaxis, quorum sensing,
      adhesion, biofilm formation) and several adaptive responses allowing the
      microorganisms to survive in a bioleaching environment. All of these are
      considered key phenomena for understanding the process of biomining. The use of
      genomics, metagenomics and high throughput proteomics to study the global
      regulatory responses that the biomining community uses to adapt to their changing
      environment is just beginning to emerge in the last years. These powerful
      approaches are reviewed here since they offer the possibility of exciting new
      findings that will allow analyzing the community as a microbial system,
      determining the extent to which each of the individual participants contributes
      to the process, how they evolve in time to keep the conglomerate healthy and
      therefore efficient during the entire process of bioleaching.

PMID- 16288846
TI  - Increases in stimulated secretion of proinflammatory cytokines by blood monocytes
      following arousal of negative affect: the role of insulin resistance as
      moderator.
AB  - We examined the effect of negative affect on changes in stimulated secretion of
      cytokines by blood monocytes and determined whether insulin resistance (IR), as
      indexed by the Homeostasis Model Assessment (HOMA), moderated these associations
      in 58 healthy men (aged 18-65 years). Blood samples and ratings of negative
      affect were collected at rest and 15min following subjects' participation in the
      Anger Recall Interview (ARI). Assessment of lipopolysaccharide (LPS)-stimulated
      secretion of IL-1beta, IL-6, and TNF-alpha was accomplished by ELISA of
      supernatant. Regression models controlling for age, body mass index, and
      race/ethnicity revealed that higher HOMA-IR values were associated with larger
      stress-induced increases in IL-1beta and TNF-alpha (p<.05). Furthermore, arousal
      of negative affect during the ARI was differentially associated with stress
      induced changes in stimulated secretion of TNF-alpha and IL-6 as a function of
      HOMA-IR (p<.05). Increases in stimulated cytokine secretion were associated with
      arousal of negative affect, but only among men with higher HOMA-IR values. Among
      men with lower HOMA-IR values, arousal of negative affect was associated with
      diminished cytokine secretion. Collectively, these data suggest that the HOMA-IR
      moderates the impact that arousal of negative affect has on the ability of blood
      monocytes to secrete inflammatory cytokines in response to LPS. Stress-induced
      increases in cytokine secretion among high HOMA-IR men are consistent with the
      role of inflammation in cardiovascular disease, hypertension, type 2 diabetes as
      well as the metabolic syndrome and underscore the relevance of negative affect in
      the etiology of these inflammatory conditions.

PMID- 16288847
TI  - Role of Smad proteins in the regulation of NF-kappaB by TGF-beta in colon cancer
      cells.
AB  - Nuclear factor kappa B (NF-kappaB) has been implicated in cancer cell survival.
      We explored the role of the TGF-beta pathway in the regulation of NF-kappaB in
      colon cancer cells. TGF-beta-1 treatment of the colon adenocarcinoma cell line
      FET-1, results in an early increase in IkappaB-alpha phosphorylation that
      precedes NF-kappaB nuclear translocation and DNA binding activity. Activation of
      the TGF-beta type I receptor is required for the TGF-beta-mediated activation of
      NF-kappaB. No activation of NF-kappaB is observed in a Smad4 null cell line,
      SW480, even though TGF-beta does result in IkappaB-alpha phosphorylation in these
      cells. Smad4 restores the TGF-beta-1-mediated NF-kappaB activation in SW480
      cells. TGF-beta-1 treatment fails to activate NF-kappaB or phosphorylate IkappaB
      alpha in FET-1 cells expressing the inhibitory Smad, Smad7. Taken together, these
      results suggest a role for Smad4 in the transcriptional activation of NF-kappaB,
      and a direct effect of Smad 7 inhibiting IkappaB-alpha phosphorylation rather
      than through the well-established inhibition of Smad2/3 phosphorylation with
      subsequent inhibition of the TGF-beta pathway.

PMID- 16288848
TI  - A peculiar site of leiomyosarcoma: the tongue tip--report of a case.
AB  - Primary leiomyosarcoma of the tongue is an exceedingly rare malignant mesenchymal
      tumour, which is hardly ever addressed in the differential diagnosis of a tongue
      lesion. Only 7 cases of this tumour have been documented in English-language
      medical literature. This study reports an additional case of primary
      leiomyosarcoma of the tongue in a 54-year-old woman, presenting with a foreign
      body sensation at the tip of the tongue with a rapidly and progressively
      enlarging ulcerative nodule. The patient received tumour excision with a 1-year
      follow-up without evidence of local recurrence or distant metastasis.
      Leiomyosarcoma in this unusual site seems to have better prognosis than
      elsewhere, although the number of cases are too small to draw a conclusion. This
      study further reviews the literature review and discusses the clinico
      pathological presentation of this peculiar rare tongue lesion.

PMID- 16288849
TI  - Aberrant expression of beta- and gamma-catenin is an independent prognostic
      marker in oral squamous cell carcinoma.
AB  - Alteration in expression of E-cadherin and catenins is associated with loss of
      differentiation, acquisition of an invasive phenotype and poor clinical outcome
      in many types of cancer. To identify molecular prognostic markers, membrane
      expression levels of E-cadherin, and alpha-, beta- and gamma-catenin in biopsy
      samples (n=135) of oral squamous cell carcinoma (OSCC) were evaluated
      immunohistochemically in relation to preoperative tumour-related features,
      clinical course and prognostic value, and were found to be significantly
      correlated with an endophytic growth pattern and pathologically proved lymph-node
      metastasis. Alteration of expression of E-cadherin, and alpha-, beta- and gamma
      catenin was also significantly correlated with poor disease-specific 5-year
      survival (P=0.0096, 0.0434, 0.0005 and 0.0005, respectively). Multivariate Cox
      proportional hazard regression analysis showed that alteration of beta- and gamma
      catenin expression was a significantly independent prognostic parameter for
      survival (P=0.0112 and 0.0088, respectively), as was the case with endophytic
      growth pattern and advanced N-category. These results indicate that patients with
      OSCC and absent or reduced membrane expression of beta- and gamma-catenin should
      be considered a high-risk group for regional lymph-node metastasis and poor
      prognosis.

PMID- 16288850
TI  - Cost-effectiveness of add-on lamotrigine therapy in clinical practice.
AB  - OBJECTIVE: This retrospective study addresses the cost-effectiveness of add-on
      therapy with lamotrigine in clinical practice. METHODS: Two years' observational
      data of 165 patients were used. Seizure frequency, adverse effects and direct
      medical costs were recorded for the year before and the year after the start of
      lamotrigine add-on therapy. Therapy effectiveness was measured by: (1) reduction
      in seizure frequency and (2) retention time. The incremental cost-effectiveness
      ratio expressed the direct medical cost per patient treated effectively with
      lamotrigine. RESULTS: The cost of medication was 492 (95% CI: 399-583) higher
      after the start of lamotrigine therapy. The extra cost of lamotrigine therapy
      (622) was partly offset by a reduction of the cost of co-medication (-130; 95%
      CI: -210 to -50). Overall, the total medical cost was 453 higher in the first
      year of lamotrigine therapy than in the year before the start of lamotrigine.
      Lamotrigine was effective in 47% of all the patients, making the resultant
      incremental cost-effectiveness ratio 954 per year. DISCUSSION: Add-on therapy of
      lamotrigine for patients with uncontrolled epilepsy offers improved health
      outcomes. Lamotrigine therapy is associated with increased cost (453) and an
      annual incremental cost-effectiveness ratio of 954. These data, together with
      utility data published in the literature, support the notion that lamotrigine
      should be considered as an add-on therapy in for patients with refractory
      epilepsy.

PMID- 16288851
TI  - Effect of 5-HT3 receptor antagonist MDL 72222 on behaviors induced by ketamine in
      rats and mice.
AB  - Phencyclidine and ketamine (but not other NMDA channel blockers, such as
      memantine) produce psychotomimetic effects. Since unlike memantine, phencyclidine
      like compounds show no significant affinity at 5-HT(3) receptors, we investigated
      if behavioral effects of ketamine could be reduced by 5HT(3) receptor blockade.
      Ketamine (3-40 mg/kg) produced ataxia, stereotypes and diminished exploratory
      activity in mice, and reduced prepulse inhibition of acoustic startle response,
      lowered accuracy in fixed consecutive number and in delayed non-matching-to
      sample tasks in rats. The 5HT(3) receptor antagonist MDL 72222 (0.3-3 mg/kg)
      administration did not reverse any of these deficits and exerted no effects on
      discriminative stimulus properties of ketamine. In the tail suspension test, both
      ketamine and MDL 72222 produced anti-immobility effects when given alone (50-66
      and 3 mg/kg, respectively) and together (12.5-25 and 1 mg/kg). The present data
      suggest that 5-HT(3) receptor blockade does not reverse the behavioral deficits
      of ketamine and may even enhance its certain effects, such as the antidepressant
      like action.

PMID- 16288852
TI  - Reduced cerebellar volume and neurological soft signs in first-episode
      schizophrenia.
AB  - Recent studies indicate that morphological and functional abnormalities of the
      cerebellum are associated with schizophrenia. Since the cerebellum is crucial for
      motor coordination, one may ask whether the respective changes are associated
      with motor dysfunction in the disease. To test these hypotheses in a clinical
      study, we investigated cerebellar volumes derived from volumetric magnetic
      resonance imaging of 37 first-episode patients with schizophrenia,
      schizophreniform or schizoaffective disorder and 18 healthy controls matched for
      age, gender and handedness. To control for potential interindividual differences
      in head size, intracranial volume was entered as a covariate. Neurological soft
      signs (NSS) were examined after remission of acute symptoms. Compared with the
      controls, patients had significantly smaller cerebellar volumes for both
      hemispheres. Furthermore, NSS in patients were inversely correlated with tissue
      volume of the right cerebellar hemisphere partialling for intracranial volume. No
      associations were detected between cerebellar volumes and psychopathological
      measures obtained at hospital admission when patients were in the acute psychotic
      state or after remission, treatment duration until remission, treatment response
      or prognostic factors, respectively. These findings support the hypothesis of
      cerebellar involvement in schizophrenia and indicate that the respective changes
      are associated with NSS.

PMID- 16288853
TI  - Comparison of regional cerebral blood flow in patients with anorexia nervosa
      before and after weight gain.
AB  - We investigated changes in regional cerebral blood flow (rCBF) before and after
      weight gain in patients with restrictive anorexia nervosa (AN-R) in comparison
      with findings in normal subjects. We assessed resting rCBF using single photon
      emission computed tomography with technetium-99m hexamethylpropylene amine oxime
      in 12 AN-R patients and 11 controls. Each patient was examined at two time
      points, at the beginning of treatment and after weight gain (average examination
      interval=88+/-26 days). Control subjects were examined only once. Before
      treatment, the AN-R group had lower rCBF in the bilateral anterior lobes,
      including the anterior cingulate cortex (ACC), and in the right parietal lobe,
      the insula, and the occipital lobes. After weight gain, the patients showed
      significant increases in the right parietal lobe and decreases in the basal
      ganglia and cerebellum in accordance with significant improvement in body weight
      and eating attitudes. However, they showed persistent decreases in the ACC area
      even after weight gain compared with findings in the controls. A significant
      positive correlation was observed between body mass index and rCBF in the
      occipital lobes in the patients. These results suggest that weight gain is
      associated with a normalization of rCBF in a number of brain areas, but that the
      low level of rCBF in the ACC at baseline is unaffected by treatment in AN-R.

PMID- 16288854
TI  - Proton spin-spin relaxation study of hydration of a model nanopore.
AB  - The hydration pattern of controlled pore glass, with pore diameter of 237 A, was
      investigated using nuclear magnetic resonance. Water proton spin-spin relaxation
      decay curves were monitored and modeled as two-component exponential decays as a
      function of hydration. The results are consistent with a geometric model
      involving a surface water layer and a bulk-like liquid fraction in the form of a
      plug. The amount of surface water increases as the sample hydrates, until
      hydration reached approximately a monolayer, at which point a water plug starts
      to form in the pore, and grow in length at the expense of the surface layer. The
      results are also analyzed in terms of, and compared to, a recently developed
      puddle pore-filling model [S.G. Allen, et al. J. Chem. Phys. 106 (1997) 7802
      7809].

PMID- 16288855
TI  - Cerebral processes in mental transformations of body parts: recognition prior to
      rotation.
AB  - There is growing evidence that the visual processing of human body stimuli is
      particular and distinct from that of other objects. This is due to implicit
      knowledge of anatomical and biomechanical constraints of the human body. The
      question arises whether body stimuli in which biomechanical constraints are
      violated are processed in the same way as realistic bodies. This study
      investigated the neural mechanisms of anatomically plausible and implausible body
      stimuli. Event-related potentials (ERP) were recorded in healthy participants
      during mental rotation of body parts. Subjects were shown pictures of body parts
      or whole bodies in which one element (finger, arm) could be anatomically accurate
      or inaccurate (e.g., left forearm attached to right upper arm). Furthermore, the
      body parts were rotated in 7 different orientations, from 0 degrees to 180
      degrees in 30 degrees increments, resulting in some possible and some impossible
      positions of the body parts. Analysis of the 123-channel ERPs was carried out by
      determining the successive segments of stable map topographies and comparing them
      between conditions. A particular segment appeared in the case of anatomically
      impossible postures at 190-230 ms followed by a segment reflecting mental
      rotation at 310-380 ms. Anatomically implausible positions are thus detected at a
      very early stage, before mental rotation occurs. Source estimations derived from
      the topographic data indicated that left occipital, bilateral frontal and two
      medial areas were activated in the case of impossible postures, whereas left
      parietal regions were strongly activated during mental rotation. This result
      contrasts with mental rotation of objects, which is considered to be a right
      parietal process.

PMID- 16288856
TI  - Microemulsion and diafiltration approaches: an attempt to maximize the global
      yield of DNA-loaded nanospheres.
AB  - The yield of DNA-loaded nanospheres in its widest definition includes
      encapsulation efficiency and the integrity of the loaded molecules plus the
      production yield of fabricated nanospheres. The former aspect could be
      considerably improved by adopting the microemulsion concept to enhance the
      stability of the primary emulsion during the preparation of nanospheres by the
      double emulsion solvent-removal method. The droplet size of the mentioned
      emulsion was monitored by means of photon electron correlation spectroscopy and
      could serve as an index for emulsion fineness and stability. DNA stability as a
      function of applied mechanical stress was monitored by horizontal agarose gel
      electrophoresis. The impact of the primary emulsion on nanosphere porosity was
      assessed as well. Regarding the second aspect of the global yield of nanospheres,
      i.e. production yield, a modified diafiltration technique was adopted for the
      washing and recovery processes in comparison with the traditional and for the
      conservation of particle size characteristics of the recovered nanospheres.

PMID- 16288857
TI  - Preparation of protein loaded poly(D,L-lactide-co-glycolide) microparticles for
      the antigen delivery to dendritic cells using a static micromixer.
AB  - The cellular immune response against tumors, viruses, or intracellular bacteria
      requires adequate antigen delivery to professional phagocytes, their processing
      and the presentation of antigenic peptides to T-cells. Biodegradable
      microparticles to enhance antigen phagocytosis and the response of cytotoxic
      lymphocytes have been proposed. The aim of the present study was to formulate
      poly(lactide-co-glycolide) (PLGA) microparticles using a w/o/w solvent
      evaporation procedure in order to obtain suitable vehicles for vaccination.
      Bovine serum albumin bearing fluorescein isothiocyanate (FITC-BSA) was used as a
      model antigen. For microparticle preparation a static micromixer was employed.
      Microparticles of 2-3 microm can be produced with good reproducibility by
      applying high flow rates at the micromixer. Microparticles with a smooth surface
      and only one pore were observed using scanning electron microscopy (SEM).
      Confocal laser scanning microscopy (CLSM) allowed localisation of the FITC-BSA
      near the surface of the microparticle. Microencapsulation of FITC-BSA did not
      altered the polymer characteristics, as determined by measuring the glass
      transition temperature. Additionally we could determine residual methylene
      chloride, employed as solvent in microparticle preparation, to be less than
      1/1000 of the USP and Ph. Eur. limit. The microparticles described herein were
      able to deliver the model antigen to human dendritic cells (DC).

PMID- 16288858
TI  - Assessing the costs of chronic obstructive pulmonary disease: the state medicaid
      perspective.
AB  - BACKGROUND: State Medicaid programs provide insurance coverage to over 40 million
      Americans. However, estimates of the annual cost of chronic obstructive pulmonary
      disease (COPD) from the Medicaid perspective are lacking. METHODS: This
      retrospective cohort study used Medicaid administrative claims data from
      California and Florida to estimate COPD expenditures using two alternative
      methods: (1) excess costs (comparing a COPD cohort to a matched comparison
      cohort); and (2) attributable costs (COPD-related expenditures within a COPD
      cohort, inclusive of respiratory medications). The COPD cohort in each state
      included Medicaid recipients not dually eligible for Medicare who were 40+ years
      of age with at least one medical claim for COPD during 2001. The comparison
      cohort consisted of patients with medical claims during 2001 for conditions other
      than chronic respiratory disease, matched by age, sex, and race to the COPD
      cohort. RESULTS: A total of 6,738 Medicaid recipients in California and 18,017 in
      Florida were included in the COPD cohort, with mean ages of 56 and 60 years,
      respectively. Comorbidities, especially congestive heart failure and vascular
      disease, were more common in the COPD cohort than among matched controls. The
      mean excess cost of COPD per-patient was estimated to be approximately 6,500 US
      dollars in California Medicaid and 5,200 US dollars in Florida Medicaid. Mean
      attributable costs of COPD were similar in the two Medicaid programs
      (approximately 2,200 US dollars and 2,300 US dollars per patient, respectively).
      CONCLUSIONS: COPD places a substantial financial burden on State Medicaid
      programs. These findings may be of interest to clinicians and policy-makers
      involved in preventing or managing this chronic disease.

PMID- 16288859
TI  - Environmental and economic analyses of waste disposal options for traditional
      markets in Indonesia.
AB  - Waste from traditional markets in Indonesia is the second largest stream of
      municipal solid waste after household waste. It has a higher organic fraction and
      may have greater potential to be managed on a business scale compared to
      household wastes. The attributed reason is that in general the wastes generated
      from traditional markets are more uniform, more concentrated and less hazardous
      than waste from other sources. This paper presents the results of environmental
      and economic assessments to compare the options available for traditional market
      waste disposal in Indonesia. The options compared were composting in labour
      intensive plants, composting in a centralised plant that utilised a simple wheel
      loader, centralised biogas production and landfill for electricity production.
      The current open dumping practice was included as the baseline case. A life cycle
      assessment (LCA) was used for environmental analysis. All options compared have
      lower environmental impacts than the current practice of open dumping. The biogas
      production option has the lowest environmental impacts. A cost-benefit analysis,
      which considered greenhouse gas savings, was used for the economic assessment. It
      was found that composting at a centralised plant is the most economically
      feasible option under the present Indonesian conditions. The approach reported in
      this study could be applied for 'a pre-feasibility first cut comparison' that
      includes environmental aspects in a decision-making framework for developing
      countries even though European emission factors were used.

PMID- 16288861
TI  - Alternative approaches for better municipal solid waste management in Mumbai,
      India.
AB  - Waste is an unavoidable by product of human activities. Economic development,
      urbanization and improving living standards in cities, have led to an increase in
      the quantity and complexity of generated waste. Rapid growth of population and
      industrialization degrades the urban environment and places serious stress on
      natural resources, which undermines equitable and sustainable development.
      Inefficient management and disposal of solid waste is an obvious cause of
      degradation of the environment in most cities of the developing world. Municipal
      corporations of the developing countries are not able to handle increasing
      quantities of waste, which results in uncollected waste on roads and in other
      public places. There is a need to work towards a sustainable waste management
      system, which requires environmental, institutional, financial, economic and
      social sustainability. This study explores alternative approaches to municipal
      solid waste (MSW) management and estimates the cost of waste management in
      Mumbai, India. Two alternatives considered in the paper are community
      participation and public private partnership in waste management. Data for the
      present study are from various non-governmental organizations (NGOs) and from the
      private sector involved in waste management in Mumbai. Mathematical models are
      used to estimate the cost per ton of waste management for both of the
      alternatives, which are compared with the cost of waste management by Municipal
      Corporation of Greater Mumbai (MCGM). It is found that the cost per ton of waste
      management is Rs. 1518 (35 US dollars) with community participation; Rs. 1797 (41
      US dollars) with public private partnership (PPP); and Rs. 1908 (44 US dollars)
      when only MCGM handles the waste. Hence, community participation in waste
      management is the least cost option and there is a strong case for
      comprehensively involving community participation in waste management.

PMID- 16288860
TI  - Urban solid waste management in Chongqing: challenges and opportunities.
AB  - The dual influences of the resource supply and protection in ecological
      environments will pose a significant challenge to China's sustainable
      development. Solid waste management offers opportunities to improve profits by
      conserving resources and improving environmental performance. This paper examines
      municipal solid waste (MSW) management in urban Chongqing, the nation's fourth
      largest municipality after Beijing, Shanghai and Tianjin. In this paper, we will
      provide information on the quantity and composition of MSW, as well as give an
      overview of different methods for collection, transport, treatment and disposal
      of MSW. At present the daily amount of MSW generated per person is about 1.08 kg;
      food waste accounts for about 59% of total MSW. MSW in Chongqing has a higher
      moisture content (64.1%) and a lower LHV (3728 kJ/kg) than other cities in Asia,
      which is an obstruction for incineration. Landfills are the main method of
      disposal in Chongqing, but pollution caused by simple landfills and lack of
      backup MSW disposal capacity are becoming major problems in the main districts of
      Chongqing. In this paper, the challenges being faced and opportunities to MSW in
      Chongqing are analyzed and some suggestions are given for improving the MSW
      system in the future.

PMID- 16288862
TI  - Poly(ADP-ribose) glycohydrolase inhibitor as chemosensitiser of malignant
      melanoma for temozolomide.
AB  - Disruption of poly(ADP-ribose) polymerase (PARP) pathways by inhibitors of PARP
      catalytic domain has been shown to increase the anti-tumour activity of
      temozolomide (TMZ). Since PARP is inhibited by poly(ADP)ribosylation, herein we
      tested whether inhibition of poly(ADP-ribose) glycohydrolase (PARG) might enhance
      TMZ efficacy. The PARG inhibitor N-bis-(3-phenyl-propyl)9-oxo-fluorene-2,7
      diamide (GPI 16552) was administered in combination with TMZ to mice injected
      subcutaneously or intracranially with B16 melanoma cells. The ability of
      treatment to reduce melanoma metastatic spreading and invasion of the
      extracellular matrix was also tested. The results indicated that combined
      treatment with GPI 16552 and TMZ significantly reduced melanoma growth, increased
      life-span of mice bearing tumour at the CNS site, and decreased the ability of
      melanoma cells to form lung metastases and to invade the extracellular matrix. In
      conclusion, PARG inhibition represents an alternative strategy to enhance TMZ
      efficacy against melanoma in peripheral as well as at CNS site.

PMID- 16288863
TI  - Sulfamoyl-4-oxoquinoline-3-carboxamides: novel potentiators of defective
      DeltaF508-cystic fibrosis transmembrane conductance regulator chloride channel
      gating.
AB  - The synthesis of a small collection of sulfamoyl-4-oxoquinoline-3-carboxamides is
      described for use as correctors of defective gating of the DeltaF508-cystic
      fibrosis transmembrane conductance regulator (CFTR) chloride channel. Several
      compounds with submicromolar potency were obtained. N-Ethyl 6
      (ethylphenylsulfamoyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (7b) was found to
      be the most effective sulfonamide corrector of defective DeltaF508-CFTR gating.

PMID- 16288864
TI  - A PNA-DNA hybridization chip approach for the detection of beta-secretase
      activity.
AB  - Developed was the addressable chip technology based on the PNA-DNA complementary
      hybridization equipped with short seven-mer PNA-encoded peptides that can be a
      versatile scaffold to monitor on-chip immunoassays. We also developed and
      validated a methodology to perform beta-secretase enzyme assay with a highly
      sensitive fashion, resulting that a peptide substrate tethering dual fluorescent
      probes allowed us to detect beta-secretase activity 10 times more sensitively
      than assays in solution.

PMID- 16288865
TI  - Angelmarin, a novel anti-cancer agent able to eliminate the tolerance of cancer
      cells to nutrient starvation.
AB  - The CH(2)Cl(2)-soluble extract of Angelica pubescens was found to kill PANC-1
      cancer cells preferentially under nutrition starvation at a concentration of 50
      microg/ml, with virtually no cytotoxicity under nutrient-rich conditions. Further
      bioassay-guided fractionation and isolation led to the isolation of a novel
      compound named angelmarin as the primary compound responsible for the
      preferential cytotoxicity; the compound exhibited 100% preferential cytotoxicity
      against PANC-1 cells at a concentration of 0.01 microg/ml.

PMID- 16288866
TI  - In silico design and synthesis of piperazine-1-pyrrolidine-2,5-dione scaffold
      based novel malic enzyme inhibitors.
AB  - Fragment-based virtual library design and virtual screening have been conducted
      against malic enzyme (ME) homology model. Several scaffolds have been identified
      as promising motifs to target ME's NADP binding site. One small focused library
      has been synthesized and tested against ME. Several compounds from this library
      have shown sub-micromolar inhibitory activity against malic enzyme.

PMID- 16288868
TI  - A neural network based classification scheme for cytotoxicity
      predictions:Validation on 30,000 compounds.
AB  - Elimination of cytotoxic compounds in the early phases of drug discovery can save
      substantial amounts of research and development costs. An artificial neural
      network based approach using atomic fragmental descriptors has been developed to
      categorize compounds according to their in vitro human cytotoxicity. Fragmental
      descriptors were obtained from the Atomic7 linear logP calculation method
      implemented in Pallas PrologP program. We used cytotoxicity values obtained from
      an in-house screening campaign of a diverse set of 30,000 drug-like molecules.
      The training set included only the most and least toxic 12,998 compounds,
      however, cytotoxicity data for all compounds were used for validation. The
      proposed approach can be safely used for filtering out potentially cytotoxic
      candidates from the development pipeline before synthesis or assays during lead
      development or lead optimisation. The trained neural network misclassified less
      than 5% percent of the non-toxic and 9% of the toxic compounds.

PMID- 16288867
TI  - Synthesis of the novel series of bispyridinium compounds bearing (E)-but-2-ene
      linker and evaluation of their reactivation activity against chlorpyrifos
      inhibited acetylcholinesterase.
AB  - Six potential AChE reactivators were synthesized using modification of currently
      known synthetic pathways. Their potency to reactivate AChE inhibited by
      insecticide chlorpyrifos was tested in vitro. According to the results, (E)-1-(2
      hydroxyiminomethylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene
      dibromide seems to be the most potent AChE reactivator. The reactivation potency
      of these compounds depends on structural factors such as constitution of the
      linking chain between both pyridinium rings, position of the oxime moiety at the
      pyridinium ring and presence of quaternary nitrogens.

PMID- 16288870
TI  - The effect of dantrolene sodium in Very Long Chain Acyl-CoA Dehydrogenase
      Deficiency.
AB  - We present a patient, who experienced recurrent episodes of rhabdomyolysis. Her
      beneficial response to treatment with dantrolene sodium was previously reported.
      Adult onset Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) deficiency has been
      diagnosed only recently. In adults, VLCAD deficiency results in recurrent fasting
      , exercise-, or infection-induced muscle stiffness, muscle pain and myoglobinuria
      caused by rhabdomyolysis. This case illustrates for the first time the beneficial
      effect of dantrolene in VLCAD deficiency. We discuss the therapeutic mechanism of
      dantrolene sodium and its possible role as additional treatment modality for
      patients with VLCAD deficiency.

PMID- 16288869
TI  - Sub-cellular localisation of fukutin related protein in different cell lines and
      in the muscle of patients with MDC1C and LGMD2I.
AB  - MDC1C and LGMD2I are two allelic forms of muscular dystrophies caused by
      mutations in the gene encoding for fukutin related protein (FKRP). FKRP encodes
      for a putative glycosyltransferase, the precise function of which is unknown.
      However, the marked reduction of alpha-dystroglycan glycosylation in the muscle
      of MDC1C and LGMD2I patients suggests a role for FKRP in dystroglycan processing.
      Using a polyclonal antibody raised against FKRP we now show that endogenous FKRP
      locates to the Golgi apparatus of neuronal, oligodendroglial, and the cardiac
      muscle cell line H9c2. In differentiated C2C12 myotubes and in transverse
      sections of normal skeletal and cardiac muscle, endogenous FKRP surrounded the
      myonuclei. This localisation was unaffected in the skeletal muscle of patients
      with MDC1C and LGMD2I carrying various FKRP mutations. These observations imply a
      specific role for FKRP during striated muscle, neuronal and glial development and
      suggest that protein mis-localisation is not a common mechanism of disease in
      FKRP-related dystrophies.

PMID- 16288871
TI  - The differential gene expression profiles of proximal and distal muscle groups
      are altered in pre-pathological dysferlin-deficient mice.
AB  - The selective pattern of muscle involvement is a key feature of muscular
      dystrophies. Dysferlinopathy is a good model for studying this process since it
      shows variable muscle involvement that can be highly selective even in individual
      patients. The transcriptomes of proximal and distal muscles from wildtype
      C57BL/10 and dysferlin deficient C57BL/10.SJL-Dysf mice at a prepathological
      stage were assessed using the Affymetrix oligonucleotide-microarray system. We
      detected significant variation in gene expression between proximal and distal
      muscle in wildtype mice. Dysferlin defiency, even in the absence of pathological
      changes, altered this proximal distal difference but with little specific overlap
      with previous microarray analyses of dysferlinopathy. In conclusion, proximal and
      distal muscle groups show distinct patterns of gene expression and respond
      differently to dysferlin deficiency. This has implications for the selection of
      muscles for future microarray analyses, and also offers new routes for
      investigating the selectivity of muscle involvement in muscular dystrophies.

PMID- 16288872
TI  - Major myofibrillar changes in early onset myopathy due to de novo heterozygous
      missense mutation in lamin A/C gene.
AB  - Mutations in the lamin A/C gene (LMNA) have been associated with neuromuscular
      diseases and more complex syndromes, involving bone and adipose tissue. We report
      on a case of early onset myopathy due to a heterozygous LMNA mutation in exon 9,
      characterized by the presence of a marked number of cytoplasmic bodies with
      extensive myofibrillar abnormalities and Z-disk disruption in skeletal muscle.
      This case suggests there is a need to increase the list of genes to be screened
      in patients with myofibrillar myopathy.

PMID- 16288873
TI  - Defining alpha-skeletal and alpha-cardiac actin expression in human heart and
      skeletal muscle explains the absence of cardiac involvement in ACTA1 nemaline
      myopathy.
AB  - Mutations in alpha-skeletal actin (ACTA1) underlie several congenital muscle
      disorders including nemaline myopathy (NM). Almost all ACTA1-NM patients have
      normal cardiac function, and, even lethally affected congenital NM patients
      exhibit an unremarkable gestation with decreased foetal movement just prior to
      birth. Although alpha-skeletal actin is thought to be the predominant sarcomeric
      actin in human heart (Boheler KR, Carrier L, de la Bastie D, et al. Skeletal
      actin mRNA increases in the human heart during ontogenic development and is the
      major isoform of control and failing adult hearts. J Clin Invest 1991;88:323-30
      ), ACTA1-NM patients almost never exhibit a cardiac phenotype. In this study, we
      define the relative expression of skeletal and cardiac actin proteins in human
      heart and skeletal muscle. We show that alpha-cardiac actin is the predominant
      sarcomeric isoform in human donor hearts and in early foetal skeletal muscle
      development. Skeletal actin is the predominant isoform from 25 to 27 weeks
      gestation and is the exclusive isoform expressed in muscle from infancy through
      to adulthood. These findings are consistent with clinical observations of NM
      patients and assist us to better understand the pathogenesis of inherited
      myopathies and cardiomyopathies with mutations in actin.

PMID- 16288874
TI  - Co-segregation of LMNA and PMP22 gene mutations in the same family.
AB  - We report here clinical, electrophysiological, and molecular findings in a family
      affected with two inherited genetic diseases: limb girdle muscular dystrophy type
      1B (LGMD1B) and hereditary neuropathy with liability to pressure palsies (HNPP).
      Members of the family carry a novel missense mutation in the LMNA gene and a
      nonsense mutation in the PMP22 gene. Interestingly, the double LMNA/PMP22
      mutations carriers showed clinical features more severe than usually seen in
      HNPP, and electrophysiological findings suggesting an axonal loss in addition to
      a typical myelinopathy. This study provides further insights into the relevance
      of lamin A/C in muscle and nerve.

PMID- 16288875
TI  - Mutations in mtDNA-encoded cytochrome c oxidase subunit genes causing isolated
      myopathy or severe encephalomyopathy.
AB  - We report on clinical, histological and genetic findings in two patients carrying
      novel heteroplasmic mutations in the mitochondrial cytochrome c oxidase subunit
      genes COII and COIII. The first patient, a 35 year-old man had a multisystemic
      disease, with clinical symptoms of bilateral cataract, sensori-neural hearing
      loss, myopathy, ataxia, cardiac arrhythmia, depression and short stature and
      carried a 7970 G>T (E129X) nonsense mutation in COII. A sudden episode of
      metabolic encephalopathy caused by extremely high blood lactate lead to coma. The
      second patient developed exercise intolerance and rhabdomyolysis at age 22 years.
      A heteroplasmic missense mutation 9789 T>C (S195P) was found in skeletal muscle,
      but not in blood and myoblasts pointing to a sporadic mutation. Our report of two
      patients with isolated COX deficiency and new mutations in COX subunit genes may
      help to draw more attention to this type of mtDNA defects and provide new aspects
      for counselling affected families.

PMID- 16288876
TI  - Standards for follow-up care of patents with breast cancer.

PMID- 16288877
TI  - Lipase-catalyzed preparation of optically active 1'-acetoxychavicol acetates and
      their structure-activity relationships in apoptotic activity against human
      leukemia HL-60 cells.
AB  - Structure-activity relationships of 1'-acetoxychavicol acetate (ACA) for
      apoptotic activity against human leukemia HL-60 cells were investigated using
      optically active ACA and various racemic ACA analogues. Natural-type (or with
      different acyl group) ACA showed a high apoptotic activity, but the ortho or meta
      isomers, 4-deacetoxy analogue, and the 2'-3' dehydrogenated derivative had no
      effect, or a weak activity. Optically active (R)- and (S)-ACA were prepared by a
      lipase-catalyzed esterification. Using a mixture of vinyl acetate-tetrahydrofuran
      (1:1 v/v) as a solvent at refluxing temperature, optically pure (R)- and (S)-ACA
      were obtained (99.7% ee and 99.1% ee, respectively). The apoptosis-inducing
      effects of both enantiomers were compared by means of an MTT assay and the
      detection of typical apoptotic phenomena (DNA fragmentation, caspase-3
      activation, and PARP cleavage) and these two activities were almost equal. These
      results indicate that the essential moieties of ACA for apoptotic activity
      against HL-60 cells are both the presence of a 4-acetoxyl group and an
      unsaturated double bond between C-2' and C-3', and that the configuration at the
      1'-position is unrelated to activity.

PMID- 16288878
TI  - Synthesis and characterization of selective dopamine D2 receptor antagonists.
AB  - A series of indole compounds have been prepared and evaluated for affinity at D2
      like dopamine receptors using stably transfected HEK cells expressing human D2,
      D3, or D4 dopamine receptors. These compounds share structural elements with the
      classical D2-like dopamine receptor antagonists, haloperidol, N-methylspiperone,
      and benperidol. The compounds that share structural elements with N
      methylspiperone and benperidol bind non-selectively to the D2 and D3 dopamine
      receptor subtypes. However, several of the compounds structurally similar to
      haloperidol were found to (a) bind to the human D2 receptor subtype with
      nanomolar affinity, (b) be 10- to 100-fold selective for the human D2 receptor
      compared to the human D3 receptor, and (c) bind with low affinity to the human D4
      dopamine receptor subtype. Binding at sigma (sigma) receptor subtypes, sigma1 and
      sigma2, were also examined and it was found that the position of the methoxy
      group on the indole was pivotal in both (a) D2 versus D3 receptor selectivity and
      (b) affinity at sigma1 receptors. Adenylyl cyclase studies indicate that our
      indole compounds with the greatest D2 receptor selectivity are neutral
      antagonists at human D2 dopamine receptor subtypes. With stably transfected HEK
      cells expressing human D2 (hD2-HEK), these compounds (a) have no intrinsic
      activity and (b) attenuated quinpirole inhibition of adenylyl cyclase. The D2
      receptor selective compounds that have been identified represent unique
      pharmacological tools that have potential for use in studies on the relative
      contribution of the D2 dopamine receptor subtypes in physiological and behavioral
      situations where D2-like dopaminergic receptor involvement is indicated.

PMID- 16288879
TI  - Synthesis of 26,27-bisnorcastasterone analogs and analysis of conformation
      activity relationship for brassinolide-like activity.
AB  - Three castasterone (CS) derivatives with varied side-chain moieties, 26,27
      bisnorcastasterone (20S-bisnorCS), 20-epi-26,27-bisnorcastasterone (20R
      bisnorCS), and 21,26,27-trisnorcastasterone (trisnorCS), were synthesized
      stereoselectively from either stigmasterol or dehydroisoandrosterone. The 50%
      effective doses (ED50, nmol/plant) in the concentration-response curve for
      brassinolide-like activity in the rice lamina inclination assay were determined
      to be 0.020 nmol (pED50 = 10.7) for 20S-bisnorCS, 3.2 nmol (pED50 = 8.5) for 20R
      bisnorCS, and 2.0 nmol (pED50 = 8.7) for trisnorCS. An analog containing an ester
      linkage between the steroid and the side-chain moiety of 20S-bisnorCS was also
      synthesized and its activity was evaluated to be 3.2 nmol (pED50 = 8.5), being
      equipotent to 20R-bisnorCS and trisnorCS. The activity of 20S-bisnorCS was 1/40
      that of CS. The conformation analysis was conducted using a systematic search,
      showing that the activity decreases with an increase in the degree of freedom of
      the side chain of the steroidal skeleton.

PMID- 16288880
TI  - Discovery of potent and selective PARP-1 and PARP-2 inhibitors: SBDD analysis via
      a combination of X-ray structural study and homology modeling.
AB  - We disclose herein our efforts aimed at discovery of selective PARP-1 and PARP-2
      inhibitors. We have recently discovered several novel classes of quinazolinones,
      quinazolidinones, and quinoxalines as potent PARP-1 inhibitors, which may
      represent attractive therapeutic candidates. In PARP enzyme assays using
      recombinant PARP-1 and PARP-2, the quinazolinone derivatives displayed relatively
      high selectivity for PARP-1 and quinoxaline derivatives showed superior
      selectivity for PARP-2, and the quinazolidinone derivatives did not have
      selectivity for PARP-1/2. Structure-based drug design analysis via a combination
      of X-ray structural study utilizing the complexes of inhibitors and human PARP-1
      catalytic domain, and homology modeling using murine PARP-2 suggested distinct
      interactions of inhibitors with PARP-1 and PARP-2. These findings provide a new
      structural framework for the design of selective inhibitors for PARP-1 and PARP
      2.

PMID- 16288881
TI  - The acetates of p-nitrophenyl alpha-L-arabinofuranoside--regioselective
      preparation by action of lipases.
AB  - All possible di-O-acetates and mono-O-acetates of p-nitrophenyl alpha-L
      arabinofuranoside were prepared by chemoenzymatic way using lipases. The 2,3-di-O
      acetate was obtained in 90% yield by deacetylation of the primary acetyl group of
      per-O-acetylated p-nitrophenyl alpha-L-arabinofuranoside by Candida cylindracea
      lipase (CCL) or Candida rugosa lipase (LAY). The 2,5- and 3,5-di-O-acetates were
      obtained by acetylation of p-nitrophenyl alpha-L-arabinofuranoside by Pseudomonas
      cepacia lipase (LPS-30) in organic solvents. The 5-O-acetate was regioselectively
      synthesised in 95% yield by acetylation of p-nitrophenyl alpha-L
      arabinofuranoside catalysed by porcine pancreas lipase. Finally, the 2- and 3-O
      acetates of p-nitrophenyl alpha-L-arabinofuranoside were obtained in two steps.
      The enzymatic di-O-acetylation of p-nitrophenyl alpha-L-arabinofuranoside by LPS
      30 was followed by enzymatic hydrolysis of the primary acetyl group by CCL or
      LAY.

PMID- 16288882
TI  - Ribonucleic guanidine demonstrates an unexpected marked preference for
      complementary DNA rather than RNA.
AB  - Replacement of the phosphodiester linkages of DNA and RNA by guanidinium linkages
      provides DNG and RNG. We report here the order of stability of mixed duplexes
      (RNG-U5.DNA-A5>>RNA-U5.RNA-A5>RNG-U5.RNA-A5>RNA-U5.DNA-A5>DNA-T5.DNA-A5). The
      considerable stability of RNG.DNA compared to RNG.RNA is shown to be due to the
      rigid backbone of RNG existing only in B-form and therefore lowering its affinity
      for A-RNA. RNG oligomers are putative antigene agents which are specific for DNA
      and would have minimal competitive binding to ncRNA.

PMID- 16288883
TI  - Anomalous "unquenching" of the fluorescence decay times of beta-lactoglobulin
      induced by the known quencher acrylamide.
AB  - Picosecond time-resolved fluorescence, together with the addition of quenching
      agents, was employed to discriminate the fluorescence contributions of the two
      tryptophans of beta-lactoglobulin (Trp19 and Trp61) to the fluorescence decays of
      the protein. The fluorescence decays of beta-lactoglobulin at pH 3, 5 and 8 are
      best fitted using sums of three exponentials and show a dominant contribution
      (98%) of the components associated with the buried Trp19, which decays according
      to a double exponential function. The addition of acrylamide (0.05 M) causes an
      increase of the decay times associated with Trp19. This effect is observed at all
      pH values studied, but the effect is stronger at pH 3 and pH 5, than at pH 8. The
      unexpected increase of the decay times of Trp19 and the variation of the
      respective amplitudes were rationalized in terms of alterations of Trp19
      mobility. The hindrance of Trp19 upon acrylamide binding was also monitored and
      supported by fluorescence anisotropy measurements.

PMID- 16288884
TI  - Cell migration and invasion assays.
AB  - The processes of cell migration and invasion are integral to embryonic
      development and the functioning of adult organisms. Deregulation of these
      processes contributes to numerous diseases. Ras GTPases and in particular members
      of the Rho subfamily of GTPases play critical roles in cell migration and
      invasion. Here, we provide a collection of protocols to assay these functions. We
      describe two cell migration assays. The monolayer wound healing assay is very
      easy to implement, whereas the microliter-scale migration assay allows
      examination of cell behavior on defined extracellular matrices. We also describe
      two methods that allow the quantification of tumor cell invasion, a versatile
      transwell Matrigel invasion assay and an organotypic assay that examines the
      invasion of glioma cells through a rat brain slice.

PMID- 16288885
TI  - Production and use of a cell permeable inhibitor of group A Paks (TAT-PID) to
      analyze signal transduction.
AB  - The Rho-family GTPases Cdc42 and Rac regulate a large number of important
      cellular processes, including motility, adhesion, proliferation, and survival.
      Among the key effectors for these GTPases are the p21-activated kinases. Although
      no specific chemical inhibitor has been developed against these enzymes, an
      inhibitory peptide derived from the N-terminus of these kinases is able to act in
      trans to suppress the activity of the full-length kinase. Here, we describe a
      method to deliver the inhibitory fragment into cells, using the recently
      described TAT system for protein transduction. This method is easy to use and is
      effective for transducing many different cell types, including those refractory
      to standard plasmid transfection. Use of the TAT-based inhibitor provides a
      specific means to suppress a single group of Cdc42 and Rac effectors, which is
      useful in analyzing their function.

PMID- 16288886
TI  - Analysis of Ras:RasGEF interactions by phage display and static multi-angle light
      scattering.
AB  - Molecular switches such as small GTPases of the Ras family cycle between inactive
      GDP-bound and active GTP-bound states. Their essential role in controlling
      development and cell homeostasis requires mechanisms which determine amplitude
      and timing of activation. This is achieved in part by the action of guanine
      nucleotide exchange factors, which function as highly controlled enzymes whose
      activity relies on spatial segregation and intra- and intermolecular regulation.
      Here, we describe two experimental methodologies that permit the identification
      and characterization of GTPase binding sites on activators by assaying complex
      formation within a broad range of affinities. In the first assay system, proteins
      presented on the surface of filamentous phage are used to probe affinity
      determinants of protein-protein interactions. In this application, a protein
      displayed phage library is generated by random mutagenesis and a plate-based
      selection is performed to identify mutations that confer higher binding affinity
      to an immobilized target. The second method uses light scattering as a tool for
      measuring the molecular weight, stoichiometry, and polydispersity of protein
      complexes in solution. In this application, conventional gel filtration
      chromatography provides initial fractionation, and in-line light scattering
      measurements allow accurate determination of molar masses of the eluent. This
      technique also provides information about conformational homogeneity which can be
      used as a quality

PMID- 16288887
TI  - Real-time in vitro measurement of GTP hydrolysis.
AB  - Small GTPases require an active GTPase activity to function correctly in their
      cellular environment. Mutation of key residues involved in this activity renders
      the GTPase defective and the small G-protein constitutively active (GTP-locked).
      The GTPase activity is also a target for GTPase-activating proteins (GAPs) which
      act to attenuate GTPase signalling by accelerating the conversion of bound GTP to
      bound GDP. The measurement of GTP hydrolysis in vitro can therefore provide
      information on the intrinsic activity of the small GTPase (e.g., mutated GTPase
      activity) as well as help define GAP specificity. Current methods to measure GTP
      hydrolysis in vitro utilise either radioactivity-based filter-binding assays or
      measurements of GDP:GTP:P(i) ratios by high-performance liquid chromatography
      (HPLC). Both provide timed snapshots of the current GTP-bound state, can be prone
      to experimental errors, and do not provide a real-time observation of GTP
      hydrolysis. The method we describe here utilises a fluorescently labelled,
      phosphate-binding protein (PBP), which scavenges for free inorganic phosphate
      (P(i)). On binding of a single P(i), a change of protein conformation is coupled
      to a 7-fold increase in fluorescence of the fluorophore. This method therefore
      permits real-time monitoring of GTPase activity, through measurement of P(i)
      production. This review describes the process of preparing and labelling the PBP
      with the MDCC fluorophore, as well as an example of its use in measuring the
      GTPase activity of small GTPases. We also discuss the pros and cons, and
      implications of the technique in comparison to the radioactive and HPLC method of
      measuring the GTPase activity.

PMID- 16288889
TI  - Photobleaching approaches to investigate diffusional mobility and trafficking of
      Ras in living cells.
AB  - Recent advances in our understanding of the intracellular trafficking, membrane
      microenvironment, and subcellular sites of signaling of Ras have been driven by
      observations of GFP-tagged Ras in living cells. Here, we describe methods to gain
      further insight into the regulation of these events through the use of
      quantitative fluorescence microscopy. We focus on three techniques, fluorescence
      recovery after photobleaching (FRAP), fluorescence loss in photobleaching (FLIP),
      and selective photobleaching. While all of these techniques exploit
      photobleaching as a tool to monitor protein dynamics, they each provide a unique
      subset of information. In particular, FRAP provides measurements of protein
      mobility via lateral diffusion by monitoring recovery of fluorescence into a
      region following a single photobleaching event. FLIP assesses the level of
      continuity and communication between subcellular compartments by repetitively
      photobleaching a region of interest and following concomitant loss of
      fluorescence from other areas in the cell. Selective photobleaching reveals
      kinetic information about active and passive transport of proteins into
      organelles such as the Golgi complex or between areas of protein enrichment such
      as caveolae. We describe how to implement these techniques using commercially
      available confocal microscopes and outline methods for data analysis. Finally, we
      discuss how these approaches are being used to provide new insights into the
      mechanisms of membrane microdomain localization, vesicular versus non-vesicular
      transport, and kinetics of exchange of Ras on and off of cell membranes.

PMID- 16288888
TI  - Electron microscopic imaging of Ras signaling domains.
AB  - Ras isoform-specific signaling from the plasma membrane appears to be regulated
      by interactions with distinct functional microdomains. We have developed
      protocols allowing the generation of 2-D spatial maps describing cell surface
      microdomain distributions. The combined electron microscopic (EM)-statistics
      approach provides nanometer scale resolution allowing both inner and outer
      leaflet domains to be visualized and cross-correlated with each other or with a
      protein of interest. In particular, the technique has allowed the interaction of
      Ras isoforms with signaling microdomains and proteins regulating these
      compartments to be screened. By allowing detailed monitoring of cell surface
      organization and compartmentalization, the approach has widespread potential for
      studies of plasma membrane-dependent cell biology, including regulated signaling
      and membrane trafficking.

PMID- 16288890
TI  - Monitoring spatio-temporal regulation of Ras and Rho GTPase with GFP-based FRET
      probes.
AB  - GFP-based fluorescence resonance energy transfer (FRET) probes that visualize
      local activity-changes of Ras and Rho GTPases in living cells are now available
      for examining the spatio-temporal regulation of these proteins. This article
      describes principles and strategies to develop intramolecular FRET probes for Ras
      and Rho-family GTPases. The procedure for characterizing candidate probes, and
      image acquisition and processing are also explained. An optimal FRET probe should
      have (i) a wide dynamic range (which means a high sensitivity), (ii) a high
      fluorescence intensity, (iii) target specificity, and (iv) a minimal perturbation
      to endogenous signaling cascades. Although an improvement of FRET probes should
      be executed in a trial-and-error manner, practical tips for optimization are
      provided here. In addition, we illustrate some applications of FRET probes for
      neuronal cells, which are composed of diverse subcellular compartments with
      different functions; thus, tools to decipher the dynamics of GTPase activity in
      each compartment have long been desired.

PMID- 16288891
TI  - Visual monitoring of post-translational lipid modifications using EGFP-GTPase
      probes in live cells.
AB  - Modification of small GTPases by lipids is required for their proper subcellular
      localization and biological activity. Lipids added post-translationally include
      both farnesyl and geranylgeranyl isoprenoids and the fatty acid palmitate. Thus,
      specific small molecule inhibitors of these processes cause mislocalization of
      small GTPases and impair their biological activity. Common biochemical methods of
      determining the lipid modification status or inhibitor sensitivity of small
      GTPases, such as in vitro prenylation assays, SDS-PAGE mobility shifts or
      metabolic labeling, although highly useful in their own right, cannot distinguish
      differences among specific subpopulations of cells, link lipid modification
      status with other properties of interest, or provide spatio-temporal information.
      An alternative method takes advantage of the tight link between small GTPase
      lipid modification and subcellular localization. The innate localization pattern
      of the enhanced green fluorescent protein, a common epitope tag frequently used
      in live cell imaging, is altered by fusion to modified but not unmodified small
      GTPases. We describe here a technique that takes advantage of these properties to
      monitor post-translational modifications of these proteins in a rapid, visual
      manner in live cells.

PMID- 16288892
TI  - In vitro refolding of recombinant human free secretory component using
      equilibrium gradient dialysis.
AB  - Human secretory component (SC) is associated with secretory immunoglobulins (IgA
      and IgM) and serves to protect the immunoglobulin in the harsh mucosal
      environment. SC is derived from the polymeric immunoglobulin receptor (pIgR)
      which transports polymeric immunoglobulins across epithelial cells into
      secretions. In this present study, we describe the first cloning, expression, in
      vitro refolding and purification of a free form of human secretory component
      (rSC) containing the five functional ligand binding domains using Escherichia
      coli BL21 (DE3). Free rSC was refolded from inclusion bodies by equilibrium
      dialysis after purification by nickel affinity chromatography under denaturing
      conditions. Refolded rSC was purified by gel filtration chromatography. Surface
      plasmon resonance and dot blot association analysis have shown that purified rSC
      binds IgM with a physiological equilibrium dissociation constant (KD) of 4.6x10(
      8) M and shares structural similarity to native SC. This provides an important
      step in the elucidation of the structure of this immunologically important
      receptor.

PMID- 16288893
TI  - Cortical plasticity following surgical extension of lower limbs.
AB  - Human cortical plasticity has been studied after peripheral sensory alterations
      due to amputations or grafts, while sudden 'quasi-physiological' changes in the
      dimension of body parts have not been investigated yet. We examined the cortical
      reorganization in achondroplastic dwarfs submitted to progressive elongation (PE)
      of lower limbs through the Ilizarov technique. This paradigm is ideal for
      studying cortical plasticity because it avoids the perturbation connected with
      deafferentation and re-afferentation. Somatosensory evoked-potentials (SEP) and
      fMRI studies were performed before and after PE during foot and knee stimulation,
      above and below the surgical fracture. A body schema test was also performed.
      Following PE, cortical modifications were observed in the primary somatosensory
      cortex for foot stimulation and in higher order somatosensory cortices for foot
      and knee. The former modifications tended to decrease 6 months after the
      elongation ending, whereas the latter tended to persist. Results are interpreted
      in terms of cortical adaptation mediated by temporary disorganization.

PMID- 16288894
TI  - Fornix, medial prefrontal cortex, nucleus accumbens, and mediodorsal thalamic
      nucleus: roles in a fear-based context discrimination task.
AB  - The goal of the present study was to evaluate the contributions of various brain
      structures anatomically and functionally linked to the hippocampus and amygdala
      in a fear-based context discrimination task. The brain areas of interest included
      the fornix, medial prefrontal cortex, mediodorsal (MD) thalamic nucleus, and
      nucleus accumbens. Damage to the MD thalamic nucleus and medial prefrontal cortex
      produced the largest impairment in context-specific fear responses. Damage to the
      fornix impaired some fear responses (freezing, ultrasonic vocalizations,
      defecation, and approach/avoidance) while leaving conditioned fear expression of
      heart rate and urination unaltered. Damage to the nucleus accumbens was also
      coupled with deficits in the discriminative expression of some (heart rate,
      urination, and ultrasonic vocalizations) but sparing of context-appropriate
      freezing, defecation, and approach/avoidance behaviors.

PMID- 16288895
TI  - Elements of diabetic nephropathy in a patient with GLUT 2 deficiency.
AB  - The Fanconi-Bickel syndrome is caused by homozygosity or compound heterozygosity
      for mutations of the facilitated glucose transporter 2 gene (GLUT2). Glycogen
      accumulates in renal tubular cells and they fail to reabsorb multiple filtered
      solutes because of impairment in GLUT2-mediated efflux of glucose. We describe a
      10-year-old male child with GLUT2 deficiency who produced massive amounts of 3
      deoxyfructose (3-DF) in the kidneys. Since 3-DF is a detoxification product of a
      potent glycating agent, 3-deoxyglucosone, a precursor of advanced glycation end
      products, this suggests a massive accumulation of glucose within tubular cells
      probably as a consequence of GLUT2 deficiency. The level of 3-DF in the urine of
      this atypical patient, who also manifested renal glomerular hyperfiltration,
      microalbuminuria, and glomerular mesangial expansion, was higher than in any
      patient examined with diabetes mellitus. Elevated levels of glucose and/or its
      metabolites in renal tubular cells may be necessary but not sufficient for the
      development of both the renal tubulopathy and diabetic-like glomerular disease in
      GLUT2 deficiency.

PMID- 16288896
TI  - The fabrication of hollow spherical copper sulfide nanoparticle assemblies with 2
      hydroxypropyl-beta-cyclodextrin as a template under sonication.
AB  - 2-Hydroxypropyl-beta-cyclodextrin was used as a template to fabricate hollow
      spherical copper sulfide nanoparticle assemblies in the presence of sonication.
      The as-prepared spheres were uniform in shape and have well-defined shells
      composed of one-layered CuS nanoparticles. The interaction between the Cu ions
      and HP-beta-CD was confirmed by the FTIR. The effects of the sonication were
      studied and a possible self-assembly mechanism was discussed.

PMID- 16288897
TI  - Sensitivity of kinematics-based model predictions to optimization criteria in
      static lifting tasks.
AB  - The effect of eight different cost functions on trunk muscle forces, spinal loads
      and stability was investigated. Kinematics-based approach combined with nonlinear
      finite element modeling and optimization were used to model in vivo measurements
      on isometric forward flexions at approximately 40 degrees and approximately 65
      degrees in sagittal plane with or without a load of 180N in hands. Four nonlinear
      (summation stress(3), summation stress(2), summation force(2) and muscle fatigue)
      and four linear (summation stress, summation force, axial compression and double
      linear) criteria were considered. Predicted muscle activities were compared with
      measured EMG data. All predictions, irrespective of the cost function used,
      satisfied required kinetic, kinematics and stability conditions all along the
      spine. Four criteria (summation stress(3), summation stress(2), fatigue and
      double-linear) predicted muscle activities that qualitatively matched measured
      EMG data. The fatigue and double-linear criteria were inadequate in predicting
      greater forces in larger muscles with no consideration for their moment arms.
      Nearly the same stability margin was computed under these four cost functions. At
      the lower lumbar levels, the compression forces differed by <20% and the shear
      forces by <14% as various cost functions were considered. Smaller axial
      compression and anterior shear forces (by less than or approximately equal 6%)
      were computed when only the active components rather than the total muscle forces
      were taken as unknown in the summation stress(3) cost function. Overall, one
      single cost function of summation stress(2) or summation stress(3) rather than a
      multi-criteria one was found sufficient and adequate in yielding plausible
      results comparable with measured EMG activities and disc pressure.

PMID- 16288898
TI  - Aminoguanidine and metformin prevent the reduced rate of HDL-mediated cell
      cholesterol efflux induced by formation of advanced glycation end products.
AB  - OBJECTIVE: The mechanisms whereby advanced glycation end products (AGE)
      contribute to atherogenesis in diabetes mellitus are not fully understood. In
      this study we analyzed in vitro the influence of advanced glycated albumin (AGE
      albumin) as well as the role of the AGE inhibitors--aminoguanidine (AMG) and
      metformin (MF)--on the cell cholesterol efflux. METHODS: HDL3 and albumin
      mediated cholesterol efflux was measured in mouse peritoneal macrophages and in
      SR-BI transfected cells that had been treated along time with dicarbonyl sugars
      or AGE-albumin, both in the presence or in the absence of AMG and MF. 125I-HDL3
      cell binding and 125I-AGE-albumin cell degradation were measured.
      Carboxymethyllysine (CML) formation and SR-BI expressions were determined by
      immunoblot. RESULTS: AGE-albumin efficiently trapped cell cholesterol but
      impaired the HDL-mediated cell cholesterol efflux by decreasing HDL binding to
      the cell surface and inducing intracellular glycoxidation, without interfering
      with the SR-BI expression. Cell treatment with dicarbonyl sugars also disrupted
      the HDL-mediated cell cholesterol efflux, but this was prevented by AMG and MF
      that reduced CML formation. CONCLUSIONS: By adversely impairing the HDL-mediated
      cell cholesterol removal rate, AGE-albumin and cell glycoxidation could
      facilitate the development of premature atherosclerosis in diabetes mellitus (DM)
      and in other diseases associated with carbonyl and oxidative stress like in
      chronic uremia. Thus, drugs that prevent AGE formation may be useful to correct
      disturbances in cell cholesterol transport.

PMID- 16288899
TI  - Improving access of associated states to advanced concepts in medical telematics-
      a day before the accession to EU.
AB  - Central and Eastern Europe countries (CEEC) undertook considerable efforts to
      include themselves in the main research and development activities in the area of
      health telematics in Europe. Countries of this region demonstrate diversified
      environments of economy transformation and health care systems status. The
      transition phase to market economy brings essential risks to the healthcare
      system performance. It seems that efforts of developing e-health environment in
      CEEC could be substantially accelerated by extended co-operation with partners
      from current member states of the European Union. The PRO-ACCESS project was
      initiated in the late phase of fifth Framework Programme as supporting action. It
      focused on the transfer of current concepts in medical telematics to countries
      remaining in the pre-accession phase. The process of dissemination of up-to-date
      approaches to e-health environment development is carried out by the Krakow
      Centre of Telemedicine and is supported by leading health telematics centres in
      Europe. To accelerate the dissemination activities the network of co-operating
      centres in CEEC was established. The strategy employed within the PRO-ACCESS
      project is supposed to yield "critical mass" necessary for facilitating the e
      health development in this region of Europe. The activities employed to reach
      this objective included publishing activities, events and trainings as well as
      intake of solutions from supporting centres.

PMID- 16288900
TI  - Cerebrovascular gene linked to Alzheimer's disease pathology.
AB  - There is already considerable evidence from epidemiological, pathological and
      clinical reports that vascular factors are crucial in the pathogenesis of
      Alzheimer's disease (AD). Cerebral hypoperfusion has been shown to be a
      preclinical condition and a most accurate indicator for predicting whether people
      will develop AD. Now, a new study by Zlokovic and colleagues reveals that the
      vascular gene MEOX2 has a low expression in cultured brain endothelial cells from
      AD patients. This, together with evidence linking a dysfunctional
      cerebrovasculature to the pathogenesis of AD, suggests that the homeobox gene
      MEOX2 downregulation provides a therapeutic target to AD and a better
      understanding of this disorder.

PMID- 16288901
TI  - Recombinant herpes vector-mediated analgesia in a primate model of hyperalgesia.
AB  - Some chronic pain syndromes are characterized by episodes of intense burning and
      hyperalgesia in localized areas of skin. These sensations are thought to be
      mediated, at least in part, by the activity of damaged, unmyelinated C
      nociceptors. These phenomena were modeled by assaying responses of macaques to
      thermal and chemical stimuli that produced periodic activation and sensitization
      of C nociceptors. Upon validation of this method, a recombinant herpes simplex
      vector encoding human preproenkephalin was topically applied to the dorsal
      surface of the feet of the monkeys. Immunohistochemistry and radioimmunoassay
      revealed that enkephalin peptides were being produced in releasable pools in
      sensory neurons innervating the treated skin area. Behavioral responses evoked by
      periodic sensitization and activation of C nociceptors innervating the vector
      treated skin area revealed a substantial and long-lasting (at least 20 weeks)
      antihyperalgesic and analgesic effect limited to the areas to which the virus was
      applied. This approach may be a viable means of treating localized cutaneous
      burning pain and hyperalgesia.

PMID- 16288902
TI  - Experience using MedDRA for global events coding in HIV clinical trials.
AB  - OBJECTIVES: To assess the feasibility of coding with MedDRA, the Medical
      Dictionary for Regulatory Activities, not only serious adverse events required
      for notification but also all other events usually reported in HIV clinical
      trials. To develop an approach for MedDRA implementation within an institutional
      research unit that contributes to an efficient, concise and reproducible event
      coding. To evaluate the impact of the maintenance and the versioning of this new
      medical terminology. METHODS: MedDRA versions 3.0 and 5.0 were used for coding
      hundreds of events reported through two HIV clinical trials. The implementation
      of MedDRA consisted in the setup of a training program, guidelines to clinical
      investigators, coding rules and medical validation process. MedDRA version 6.1
      was applied to the coding made with the MedDRA version 5.0 in order to identify
      the assignments affected by the new version and to determine the impact of
      versioning. RESULTS: Coding with MedDRA all types of events in HIV clinical
      trials was feasible even though coders experienced some difficulties due mainly
      to the lack of precision in the investigator verbatim and the high specificity
      and sensitivity of MedDRA. The addition of appropriate tools to support the use
      of MedDRA improved significantly the coding of all types of events in HIV
      clinical trials. The impact of MedDRA versioning was limited and did not result
      in significant issues. The global implementation process of MedDRA required
      important resources in terms of qualified personnel, organisation and
      maintenance. CONCLUSIONS: Guidelines for investigators, coding rules and medical
      validation appeared to be mandatory for a successful implementation of MedDRA.
      The use of MedDRA, with the addition of the mentioned support tools, should
      ensure coding consistency and facilitate the clinical and tolerance analyses and
      meta-analyses in clinical trials.

PMID- 16288903
TI  - Gas chromatography/mass spectrometry characterization of urinary metabolites of
      danazol after oral administration in human.
AB  - Danazol (17alpha-pregna-2,4-dien-20-yno [2,3-d]-isoxazol-17beta-ol), is a
      synthetic derivative of ethisterone, structurally related to stanozolol. For this
      reason its use as doping agent has been investigated. Danazol (Runch) (200 mg)
      were orally administered to two healthy male volunteers. Urine samples were
      collected up to 1-week post-dose. Four new metabolites have been identified in
      addition to the five previously reported. We propose the monitorization of 6beta
      hydroxy-2-hydroxymethyl-1,2-dehydroethisterone and 6beta,16epsilon-dihydroxy
      2epsilon-hydroxymethyl-ethisterone by free fraction analysis. In a same way, we
      proposed to detect the principal isomer of a mono-hydroxylated metabolite of
      6beta-hydroxy-2epsilon-hydroxymethylethisterone in the conjugated fraction. We
      conclude that new metabolites can be included for the detection of danazol abuse
      since the main metabolite ethisterone is excreted relatively fast in urine.

PMID- 16288904
TI  - Simultaneous determination of ZT-1 and its metabolite Huperzine A in plasma by
      high-performance liquid chromatography with ultraviolet detection.
AB  - ZT-1 is a novel acetylcholinesterase (AChE) inhibitor. It is rapidly transformed
      to Huperzine A (Hup A) in vitro. A simple and rapid HPLC-UV method for the
      simultaneous determination of ZT-1 and its metabolite Hup A in plasma is
      described. The chromatographic separations were achieved on a C(18) ODS column
      (250 mm x 4.6 mm ID) using methanol-1 mmol/L ammonium acetate (70:30,v/v) as
      mobile phase. The flow rate was 0.7 mL/min, the detection wavelength was 313 nm
      and the column temperature was kept at 35 degrees C. Plasma samples were prepared
      as rapidly as possible and extracted immediately with 5 mL of chloroform:iso
      propyl alcohol mixture (v/v, 9:1). The retention times of ZT-1 and Huperzine A
      (Hup A) were 18.7 and 14.4 min, respectively. The mean absolute recoveries of two
      analytes were >90%. Quantification limits were all 0.02 nmol/mL for ZT-1 and Hup
      A. This analytical method was reliable and convenient procedure that meets the
      criteria for the pharmacokinetic evaluation of ZT-1 on experimental animals.

PMID- 16288905
TI  - Presence of the storage seed protein vicilin in internal organs of larval
      Callosobruchus maculatus (Coleoptera: Bruchidae).
AB  - Variant vicilins (7S storage globulins) of cowpea seeds (Vigna unguiculata) are
      considered as the main resistance factor present in some African genotypes
      against the bruchid Callosobruchus maculatus. It has been suggested that the
      toxic properties of vicilins may be related to their recognition and interaction
      with glycoproteins and other membrane constituents along the digestive tract of
      the insect. However, the possibility of a systemic effect has not yet been
      investigated. The objective of this work was to study the fate of 7S storage
      globulins of V. unguiculata in several organs of larvae of the cowpea weevil C.
      maculatus. Results demonstrated binding of vicilins to brush border membrane
      vesicles, suggesting the existence of specific receptors. Vicilins were detected
      in the haemolymph, in the midgut, and in internal organs, such as fat body and
      malpighian tubules. There is evidence of accumulation of vicilins in the fat body
      of both larvae and adults. The absorption of vicilins and their presence in
      insect tissues parallels classical sequestration of secondary compounds.

PMID- 16288906
TI  - Factors influencing in vitro infectivity and growth of Rickettsia peacockii
      (Rickettsiales: Rickettsiaceae), an endosymbiont of the Rocky Mountain wood tick,
      Dermacentor andersoni (Acari, Ixodidae).
AB  - Rickettsia peacockii, a spotted fever group rickettsia, is a transovarially
      transmitted endosymbiont of Rocky Mountain wood ticks, Dermacentor andersoni.
      This rickettsia, formerly known as the East Side Agent and restricted to female
      ticks, was detected in a chronically infected embryonic cell line, DAE100, from
      D. andersoni. We examined infectivity, ability to induce cytopathic effect (CPE)
      and host cell specificity of R. peacockii using cultured arthropod and mammalian
      cells. Aposymbiotic DAE100 cells were obtained using oxytetracycline or
      incubation at 37 degrees C. Uninfected DAE100 sublines grew faster than the
      parent line, indicating R. peacockii regulation of host cell growth.
      Nevertheless, DAE100 cellular defenses exerted partial control over R. peacockii
      growth. Rickettsiae existed free in the cytosol of DAE100 cells or within
      autophagolysosomes. Exocytosed rickettsiae accumulated in the medium and were
      occasionally contained within host membranes. R. peacockii multiplied in other
      cell lines from the hard ticks D. andersoni, Dermacentor albipictus, Ixodes
      scapularis, and Ixodes ricinus; the soft tick Carios capensis; and the
      lepidopteran Trichoplusia ni. Lines from the tick Amblyomma americanum, the
      mosquito Aedes albopictus, and two mammalian cell lines were non-permissive to R.
      peacockii. High cell densities facilitated rickettsial spread within permissive
      cell cultures, and an inoculum of one infected to nine uninfected cells resulted
      in the greatest yield of infected tick cells. Cell-free R. peacockii also were
      infectious for tick cells and centrifugation onto cell layers enhanced
      infectivity approximately 100-fold. The ability of R. peacockii to cause mild CPE
      suggests that its pathogenicity is not completely muted. An analysis of R.
      peacockii-cell interactions in comparison to pathogenic rickettsiae will provide
      insights into host cell colonization mechanisms.

PMID- 16288907
TI  - Redox control of K+ channel remodeling in rat ventricle.
AB  - Electrical remodeling of the diseased heart contributes to contractile
      dysfunction and arrhythmias, and is characterized by down-regulation of K(+)
      channels that control action potential morphology. We have recently shown that
      remodeling of K(+) channels underlying the transient outward current (I(to))
      involves a shift in cell redox balance that is reflected by a depletion of the
      endogenous redox buffer, glutathione (GSH). This study used a pharmacological
      model to further examine the role of redox-mediated mechanisms in regulating
      cardiac K(+) currents. Inhibition of major redox pathways was elicited in normal
      rats by daily injections of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), an
      inhibitor of thioredoxin and glutathione reductases, and buthionine sulfoximine
      (BSO), a blocker of GSH synthesis. Fluorescence microscopy studies showed that
      [GSH] in isolated ventricular myocytes was decreased ~50% from control after 3
      days of BCNU/BSO treatment (P<0.05), consistent with a shift in cell redox state.
      In voltage-clamp experiments, maximum I(to) density was decreased 33% from
      control in left ventricular myocytes from BCNU/BSO-treated rats (P<0.05), while
      the inward rectifier and steady state outward currents were not significantly
      altered. Decreased I(to) density correlated with significant decreases in Kv4.2
      mRNA and proteins levels of Kv4.2 and Kv1.4. Down-regulation of I(to) in myocytes
      from BCNU/BSO rats was reversed in vitro by exogenous GSH or N-acetylcysteine, a
      GSH precursor and antioxidant. I(to) density and [GSH] were also up-regulated by
      receptor tyrosine kinase activation with insulin or a tyrosine phosphatase
      inhibitor. The effect of these activators on I(to) was blocked by inhibitors of
      PI 3-kinase, MEK and p38 MAP kinases. These data suggest that expression of
      cardiac I(to) channels is regulated by endogenous oxidoreductase systems and that
      receptor tyrosine kinase signaling functionally impacts K(+) channel remodeling
      through its control of cell redox state.

PMID- 16288908
TI  - Glycogen synthase kinase-3beta/beta-catenin promotes angiogenic and anti
      apoptotic signaling through the induction of VEGF, Bcl-2 and survivin expression
      in rat ischemic preconditioned myocardium.
AB  - Ischemic preconditioning (IP) enhances vascular endothelial growth factor (VEGF),
      Bcl-2 and survivin expression after myocardial infarction (MI). Mechanisms of
      angiogenic and anti-apoptotic effects due to IP still remain unclear. The present
      study attempts to address whether GSK-3beta-beta-catenin signaling in turn
      interacts with T-cell transcription factor/lymphoid-enhancer binding factor
      (TCF/LEF) and regulates these genes in the ischemic preconditioned myocardium. In
      a rat MI model with permanent occlusion of left anterior descending coronary
      artery (LAD), IP (four cycles of 4-min of ischemia and 4-min of reperfusion)
      significantly phosphorylated and inhibited GSK-3beta and accumulated beta-catenin
      in the cytosol and nucleus. Wortmannin, a PI-3 kinase inhibitor, repressed this
      effect in our model. We examined whether pretreatment with GSK-3beta inhibitor
      lithium or SB216763, mimicked IP-mediated angiogenesis and cardioprotection.
      Lithium- or SB216763- treated rats revealed accumulation of cytosolic and nuclear
      beta-catenin. This was followed by increased TCF/LEF transcriptional activity and
      the upregulation of VEGF, Bcl-2 and survivin mRNA expression accompanied by
      reduction of apoptotic cardiomyocytes and endothelial cells and increased
      capillary density after MI. The results of this study demonstrate, first time
      that inhibition of GSK-3beta followed by accumulation of beta-catenin in the
      cytosol and nucleus has potent anti-apoptotic and angiogenic effects after MI and
      that the PI3-kinase/GSK-3beta/beta-catenin signaling pathway plays an important
      role in IP.

PMID- 16288909
TI  - Clemastine, a conventional antihistamine, is a high potency inhibitor of the HERG
      K+ channel.
AB  - Human ether-a-go-go-related gene (HERG) encodes the alpha-subunit of channels
      carrying the cardiac rapid delayed K+ current (Ikr), which is a major determinant
      of the duration of ventricular action potentials (APs) and of the QT interval.
      This study investigated the effects on HERG channel current (IHERG) of
      clemastine, a "conventional" antihistamine that has been associated with delayed
      ventricular repolarization in vitro, but for which no adverse effects on the
      human QT interval have been reported. Whole-cell patch-clamp measurements of
      IHERG were made at 37 degrees C from human embryonic kidney (HEK 293) cells
      stably expressing HERG channels. IHERG tails at -40 mV following depolarizing
      pulses to +20 mV were inhibited by clemastine with an IC50 value of 12 nM; this
      drug concentration also produced a marked inhibition of peak IHERG elicited
      during an AP voltage-clamp command. Clemastine produced a reversible
      approximately -5 mV shift in the IHERG steady-state voltage-dependent activation
      curve, but voltage-dependence of inactivation was unaffected. Development of
      IHERG inhibition by clemastine showed strong time-dependence. The S6 point
      mutations Y652A and F656A greatly attenuated the inhibitory effect of clemastine.
      We conclude that clemastine is a high potency inhibitor of IHERG, that this
      action is contingent upon channel gating and that clemastine interacts with a
      high affinity drug-binding site in the HERG channel pore cavity. The disparity
      between clemastine's potent IHERG inhibition and a lack of QT-prolongation in
      normal clinical use underscores the need to interpret HERG IC50 data for novel
      compounds in the context of information from other safety assays.

PMID- 16288910
TI  - In vivo expression of a conditional TGF-beta1 transgene: no evidence for TGF
      beta1 transgene expression in SM22alpha-tTA transgenic mice.
AB  - Transforming growth beta-1 (TGF-beta1) appears to play a critical role in the
      regulation of arterial intimal growth and the development of atherosclerosis. TGF
      beta1 is expressed at increased levels in diseased arteries; however, its role in
      disease development remains controversial. Experiments in which TGF-beta1 is
      overexpressed in the artery wall of transgenic mice could clarify the role of TGF
      beta1 in the development or prevention of vascular disease. However, constitutive
      overexpression of a TGF-beta1 transgene in the mouse artery wall is embryonically
      lethal. Therefore, to overexpress TGF-beta1 in the artery wall of adult mice, we
      generated mice that were transgenic for a conditional, tetracycline operator
      (tetO)-driven TGF-beta1 allele. These mice were viable, and when crossed with
      mice expressing a tetracycline-regulated transactivator (tTA) in the heart,
      expressed the TGF-beta1 transgene in a cardiac-restricted and doxycycline
      dependent manner. Nevertheless, breeding of the tetO-TGF-beta1 transgene into
      three lines of mice transgenic for a smooth muscle-targeted tTA (SM22alpha-tTA
      mice; reported elsewhere to transactivate tetO-driven alleles in smooth muscle
      cells of large arteries) did not yield expression of the TGF-beta1 transgene.
      Moreover, tTA expression was not detected in aortae of the SM22alpha-tTA mice.
      Transgenic mice that express tTA at high levels in vascular smooth muscle and
      reliably transactivate tetO-driven transgenes would be useful for deciphering the
      role of TGF-beta1 (or other proteins) in normal arterial physiology and in the
      development of arterial disease. Currently available SM22alpha-tTA mice were not
      useful for this purpose. Generation of higher-expressing lines of SM22alpha-tTA
      mice appears warranted.

PMID- 16288911
TI  - Microarray analysis to evaluate different animal models for human heart failure.

PMID- 16288912
TI  - SVA elements: a hominid-specific retroposon family.
AB  - SVA is a composite repetitive element named after its main components, SINE, VNTR
      and Alu. We have identified 2762 SVA elements from the human genome draft
      sequence. Genomic distribution analysis indicates that the SVA elements are
      enriched in G+C-rich regions but have no preferences for inter- or intragenic
      regions. A phylogenetic analysis of the elements resulted in the recovery of six
      subfamilies that were named SVA_A to SVA_F. The composition, age and genomic
      distribution of the subfamilies have been examined. Subfamily age estimates based
      upon nucleotide divergence indicate that the expansion of four SVA subfamilies
      (SVA_A, SVA_B, SVA_C and SVA_D) began before the divergence of human, chimpanzee
      and gorilla, while subfamilies SVA_E and SVA_F are restricted to the human
      lineage. A survey of human genomic diversity associated with SVA_E and SVA_F
      subfamily members showed insertion polymorphism frequencies of 37.5% and 27.6%,
      respectively. In addition, we examined the amplification dynamics of SVA elements
      throughout the primate order and traced their origin back to the beginnings of
      hominid primate evolution, approximately 18 to 25 million years ago. This makes
      SVA elements the youngest family of retroposons in the primate order.

PMID- 16288913
TI  - Asp79 makes a large, unfavorable contribution to the stability of RNase Sa.
AB  - The two most buried carboxyl groups in ribonuclease Sa (RNase Sa) are Asp33 (99%
      buried; pK 2.4) and Asp79 (85% buried; pK 7.4). Above these pK values, the
      stability of the D33A variant is 6kcal/mol less than wild-type RNase Sa, and the
      stability of the D79A variant is 3.3kcal/mol greater than wild-type RNase Sa. The
      key structural difference between the carboxyl groups is that Asp33 forms three
      intramolecular hydrogen bonds, and Asp79 forms no intramolecular hydrogen bond.
      Here, we focus on Asp79 and describe studies of 11 Asp79 variants. Most of the
      variants were at least 2kcal/mol more stable than wild-type RNase Sa, and the
      most interesting was D79F. At pH 3, below the pK of Asp79, RNase Sa is
      0.3kcal/mol more stable than the D79F variant. At pH 8.5, above the pK of Asp79,
      RNase Sa is 3.7kcal/mol less stable than the D79F variant. The unfavorable
      contribution of Asp79 to the stability appears to result from the Born self
      energy of burying the charge and, more importantly, from unfavorable charge
      charge interactions. To counteract the effect of the negative charge on Asp79, we
      prepared the Q94K variant and the crystal structure showed that the amino group
      of the Lys formed a hydrogen-bonded ion pair (distance, 2.71A; angle, 100 degrees
      ) with the carboxyl group of Asp79. The stability of the Q94K variant was about
      the same as the wild-type at pH 3, where Asp79 is uncharged, but 1kcal/mol
      greater than that of wild-type RNase Sa at pH 8.5, where Asp79 is charged.
      Differences in hydrophobicity, steric strain, Born self-energy, and electrostatic
      interactions all appear to contribute to the range of stabilities observed in the
      variants. When it is possible, replacing buried, non-hydrogen bonded, ionizable
      side-chains with non-polar side-chains is an excellent means of increasing
      protein stability.

PMID- 16288914
TI  - Structural determinants of substrate access to the disulfide oxidase Erv2p.
AB  - Erv2p is a small, dimeric FAD-dependent sulfhydryl oxidase that generates
      disulfide bonds in the lumen of the endoplasmic reticulum. Mutagenic and
      structural studies suggest that Erv2p uses an internal thiol-transfer relay
      between the FAD-proximal active site cysteine pair (Cys121-Cys124) and a second
      cysteine pair (Cys176-Cys178) located in a flexible, substrate-accessible C
      terminal tail of the adjacent dimer subunit. Here, we demonstrate that Cys176 and
      Cys178 are the only amino acids in the tail region required for disulfide
      transfer and that their relative positioning within the tail peptide is important
      for activity. However, intragenic suppressor mutations could be isolated that
      bypass the requirement for Cys176 and Cys178. These mutants were found to disrupt
      Erv2p dimerization and to increase the activity of Erv2p for thiol substrates
      such as glutathione. We propose that the two Erv2p subunits act together to
      direct the disulfide transfer to specific substrates. One subunit provides the
      catalytic domain composed of the active site cysteine residues and the FAD
      cofactor, while the second subunit appears to have two functions: it facilitates
      disulfide transfer to substrates via the tail cysteine residues, while
      simultaneously shielding the active site cysteine residues from non-specific
      reactions.

PMID- 16288915
TI  - Crystal structure of wild-type chaperonin GroEL.
AB  - The 2.9A resolution crystal structure of apo wild-type GroEL was determined for
      the first time and represents the reference structure, facilitating the study of
      structural and functional differences observed in GroEL variants. Until now the
      crystal structure of the mutant Arg13Gly, Ala126Val GroEL was used for this
      purpose. We show that, due to the mutations as well as to the presence of a
      crystallographic symmetry, the ring-ring interface was inaccurately described.
      Analysis of the present structure allowed the definition of structural elements
      at this interface, essential for understanding the inter-ring allosteric signal
      transmission. We also show unambiguously that there is no ATP-induced 102 degrees
      rotation of the apical domain helix I around its helical axis, as previously
      assumed in the crystal structure of the (GroEL-KMgATP)(14) complex, and analyze
      the apical domain movements. These results enabled us to compare our structure
      with other GroEL crystal structures already published, allowing us to suggest a
      new route through which the allosteric signal for negative cooperativity
      propagates within the molecule. The proposed mechanism, supported by known
      mutagenesis data, underlines the importance of the switching of salt bridges.

PMID- 16288917
TI  - Minimization and stabilization of the Mycobacterium tuberculosis recA intein.
AB  - Many naturally occurring inteins consist of two functionally independent domains,
      a protein-splicing domain and an endonuclease domain. In a previous study, a 168
      amino acid residue mini-intein was generated by removal of the central
      endonuclease domain of the 440 residue Mycobacterium tuberculosis (Mtu) recA
      intein. In addition, directed evolution experiments identified a mutation, V67L,
      that improved the activity of the mini-intein significantly. A recent crystal
      structure shows that the loop connecting two beta-strands from the N-terminal and
      C-terminal intein subdomains of the mini-intein is disordered. The goals of the
      present study were to generate smaller mini-intein derivatives and to understand
      the basis for reversal of the splicing defect by the V67L mutation. Guided by the
      structural information, we generated a number of derivatives 135 to 152 residues
      in length, with V67 or L67. All of the new minimal inteins are functional in
      splicing. In vivo selection experiments for function showed that by removal of
      the loop region, 137 residues may be the lower limit for full protein-splicing
      activity. In addition, the activation effect of the V67L mutation was observed to
      be universal for mini-inteins longer than 137 residues. Structural and functional
      analyses indicate that the role of the mutation is in stabilization of the mini
      intein core.

PMID- 16288916
TI  - The structure of 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase from
      Mycobacterium tuberculosis reveals a common catalytic scaffold and ancestry for
      type I and type II enzymes.
AB  - The shikimate pathway, responsible for the biosynthesis of aromatic compounds, is
      essential for the growth of Mycobacterium tuberculosis and is a potential target
      for the design of new anti-tuberculosis drugs. The first step of this pathway is
      catalyzed by 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS). The
      DAH7PSs have been classified into two apparently unrelated types and, whereas
      structural data have been obtained for the type I DAH7PSs, no structural
      information is available for their type II counterparts. The type II DAH7PS from
      M.tuberculosis has been expressed in Escherichia coli, purified, functionally
      characterized and crystallized. It is found to be metal ion-dependent and subject
      to feedback inhibition by phenylalanine, tryptophan, tyrosine and chorismate,
      with a significant synergistic effect when tryptophan is used in combination with
      phenylalanine. The crystal structure of M.tuberculosis DAH7PS has been determined
      by single-wavelength anomalous diffraction and refined at 2.3A in complex with
      substrate phosphoenolpyruvate and Mn(2+). The structure reveals a tightly
      associated dimer of (beta/alpha)(8) TIM barrels. The monomer fold, the
      arrangement of key residues in the active site, and the binding modes of PEP and
      Mn(2+), all match those of the type I enzymes, and indicate a common ancestry for
      the type I and type II DAH7PSs, despite their minimal sequence identity. In
      contrast, the structural elements that decorate the core (beta/alpha)(8) fold
      differ from those in the type I enzymes, consistent with their different
      regulatory and oligomeric properties.

PMID- 16288918
TI  - The neural repressor NRSF/REST binds the PAH1 domain of the Sin3 corepressor by
      using its distinct short hydrophobic helix.
AB  - In non-neuronal cells and neuronal progenitors, many neuron-specific genes are
      repressed by a neural restrictive silencer factor (NRSF)/repressor element 1
      silencing transcription factor (REST), which is an essential transcriptional
      repressor recruiting the Sin3-HDAC complex. Sin3 contains four paired amphipathic
      helix (PAH) domains, PAH1, PAH2, PAH3 and PAH4. A specific target repressor for
      Sin3 is likely to bind to one of them independently. So far, only the tertiary
      structures of PAH2 domain complexes, when bound to the Sin3-interacting domains
      of Mad1 and HBP1, have been determined. Here, we reveal that the N-terminal
      repressor domain of NRSF/REST binds to the PAH1 domain of mSin3B, and determine
      the structure of the PAH1 domain associated with the NRSF/REST minimal repressor
      domain. Compared to the PAH2 structure, PAH1 holds a rather globular four-helix
      bundle structure with a semi-ordered C-terminal tail. In contrast to the
      amphipathic alpha-helix of Mad1 or HBP1 bound to PAH2, the short hydrophobic
      alpha-helix of NRSF/REST is captured in the cleft of PAH1. A nuclear hormone
      receptor corepressor, N-CoR has been found to bind to the PAH1 domain with a
      lower affinity than NRSF/REST by using its C-terminal region, which contains
      fewer hydrophobic amino acid residues than the NRSF/REST helix. For strong
      binding to a repressor, PAH1 seems to require a short alpha-helix consisting of
      mostly hydrophobic amino acid residues within the repressor. Each of the four PAH
      domains of Sin3 seems to interact with a characteristic helix of a specific
      repressor; PAH1 needs a mostly hydrophobic helix and PAH2 needs an amphipathic
      helix in each target repressor.

PMID- 16288919
TI  - Molecular basis of dystrobrevin interaction with kinesin heavy chain: structural
      determinants of their binding.
AB  - Dystrobrevins are a family of widely expressed dystrophin-associated proteins
      that comprises alpha and beta isoforms and displays significant sequence homology
      with several protein-binding domains of the dystrophin C-terminal region. The
      complex distribution of the multiple dystrobrevin isoforms suggests that the
      variability of their composition may be important in mediating their function. We
      have recently identified kinesin as a novel dystrobrevin-interacting protein and
      localized the dystrobrevin-binding site on the cargo-binding domain of neuronal
      kinesin heavy chain (Kif5A). In the present study, we assessed the kinetics of
      the dystrobrevin-Kif5A interaction by quantitative pull-down assay and surface
      plasmon resonance (SPR) analysis and found that beta-dystrobrevin binds to
      kinesin with high affinity (K(D) approximately 40 nM). Comparison of the
      sensorgrams obtained with alpha and beta-dystrobrevin at the same concentration
      of analyte showed a lower affinity of alpha compared to that of beta
      dystrobrevin, despite their functional domain homology and about 70% sequence
      identity. Analysis of the contribution of single dystrobrevin domains to the
      interaction revealed that the deletion of either the ZZ domain or the coiled-coil
      region decreased the kinetics of the interaction, suggesting that the tertiary
      structure of dystrobrevin may play a role in regulating the interaction of
      dystrobrevin with kinesin. In order to understand if structural changes induced
      by post-translational modifications could affect dystrobrevin affinity for
      kinesin, we phosphorylated beta-dystrobrevin in vitro and found that it showed
      reduced binding capacity towards kinesin. The interaction between the
      adaptor/scaffolding protein dystrobrevin and the motor protein kinesin may play a
      role in the transport and targeting of components of the dystrophin-associated
      protein complex to specific sites in the cell, with the differences in the
      binding properties of dystrobrevin isoforms reflecting their functional diversity
      within the same cell type. Phosphorylation events could have a regulatory role in
      this context.

PMID- 16288920
TI  - Dual modes of modification of hepatitis A virus 3C protease by a serine-derived
      beta-lactone: selective crystallization and formation of a functional catalytic
      triad in the active site.
AB  - Hepatitis A virus (HAV) 3C proteinase is a member of the picornain cysteine
      proteases responsible for the processing of the viral polyprotein, a function
      essential for viral maturation and infectivity. This and its structural
      similarity to other 3C and 3C-like proteases make it an attractive target for the
      development of antiviral drugs. Previous solution NMR studies have shown that a
      Cys24Ser (C24S) variant of HAV 3C protein, which displays catalytic properties
      indistinguishable from the native enzyme, is irreversibly inactivated by N
      benzyloxycarbonyl-l-serine-beta-lactone (1a) through alkylation of the sulfur
      atom at the active site Cys172. However, crystallization of an enzyme-inhibitor
      adduct from the reaction mixture followed by X-ray structural analysis shows only
      covalent modification of the epsilon2-nitrogen of the surface His102 by the beta
      lactone with no reaction at Cys172. Re-examination of the heteronuclear multiple
      quantum coherence (HMQC) NMR spectra of the enzyme-inhibitor mixture indicates
      that dual modes of single covalent modification occur with a >/=3:1 ratio of S
      alkylation of Cys172 to N-alkylation of His102. The latter product crystallizes
      readily, probably due to the interaction between the phenyl ring of the N
      benzyloxycarbonyl (N-Cbz) moiety and a hydrophobic pocket of a neighboring
      protein molecule in the crystal. Furthermore, significant structural changes are
      observed in the active site of the 3C protease, which lead to the formation of a
      functional catalytic triad with Asp84 accepting one hydrogen bond from His44.
      Although the 3C protease modified at Cys172 is catalytically inactive, the singly
      modified His102 N(epsilon2)-alkylated protein displays a significant level of
      enzymatic activity, which can be further modified/inhibited by N-iodoacetyl
      valine-phenylalanine-amide (IVF) (in solution and in crystal) or excessive amount
      of the same beta-lactone inhibitor (in solution). The success of soaking IVF into
      HAV 3C-1a crystals demonstrates the usefulness of this new crystal form in the
      study of enzyme-inhibitor interactions in the proteolytic active site.

PMID- 16288921
TI  - Novel class III phosphoribosyl diphosphate synthase: structure and properties of
      the tetrameric, phosphate-activated, non-allosterically inhibited enzyme from
      Methanocaldococcus jannaschii.
AB  - The prs gene encoding phosphoribosyl diphosphate (PRPP) synthase of the
      hyperthermophilic autotrophic methanogenic archaeon Methanocaldococcus jannaschii
      has been cloned and expressed in Escherichia coli. Subsequently, M.jannaschii
      PRPP synthase has been purified, characterised, crystallised, and the crystal
      structure determined. The enzyme is activated by phosphate ions and only ATP or
      dATP serve as diphosphoryl donors. The K(m) values are determined as 2.6 mM and
      2.8 mM for ATP and ribose 5-phosphate, respectively, and the V(max) value as 2.20
      mmol (minxmg of protein)(-1). ADP is a potent inhibitor of activity while GDP has
      no effect. A single ADP binding site, the active site, is present per subunit.
      The crystal structure of the enzyme reveals a more compact subunit than that of
      the enzyme from the mesophile Bacillus subtilis, caused by truncations at the N
      and C terminus as well as shorter loops in the M.jannaschii enzyme. The
      M.jannaschii enzyme displays a tetrameric quaternary structure in contrast to the
      hexameric quaternary structure of B.subtilis PRPP synthase. Soaking of the
      crystals with 5'-AMP and PRPP revealed the position of the former compound as
      well as that of ribose 5-phosphate. The properties of M.jannaschii PRPP synthase
      differ widely from previously characterised PRPP synthases by its tetrameric
      quaternary structure and the simultaneous phosphate ion-activation and lack of
      allosteric inhibition, and, thus, constitute a novel class of PRPP synthases.

PMID- 16288922
TI  - New insights into the catalytic activation of the MAPK phosphatase PAC-1 induced
      by its substrate MAPK ERK2 binding.
AB  - PAC-1 is an inducible, nuclear-specific, dual-specificity mitogen-activated
      protein (MAP) kinase phosphatase that has been shown recently to be a
      transcription target of the human tumor-suppressor protein p53 in signaling
      apoptosis and growth suppression. However, its substrate specificity and
      regulation of catalytic activity thus far remain elusive. Here, we report in
      vitro characterization of PAC-1 phosphatase activity with three distinct MAP
      kinase subfamilies. We show that the recombinant PAC-1 exists in a virtually
      inactive state when alone in vitro, and dephosphorylates extracellular signal
      regulated kinase 2 (ERK2) but not p38alpha or c-Jun NH(2)-terminal kinase 2
      (JNK2). ERK2 dephosphorylation by PAC-1 requires association of its amino
      terminal domain with ERK2 that results in catalytic activation of the
      phosphatase. p38alpha also interacts with but does not activate PAC-1, whereas
      JNK2 does not bind to or cause catalytic activation by PAC-1. Moreover, our
      structure-based analysis reveals that individual mutation of the conserved Arg294
      and Arg295 that likely comprise the phosphothreonine-binding pocket in PAC-1 to
      either alanine or lysine results in a nearly complete loss of its phosphatase
      activity even in the presence of ERK2. These results suggest that Arg294 and
      Arg295 play an important role in PAC-1 catalytic activation induced by ERK2
      binding.

PMID- 16288924
TI  - Effects of antidepressive therapy on auditory processing in severely depressed
      patients: a combined MRS and MEG study.
AB  - BACKGROUND: Alterations in brain metabolism as well as in brain function in
      different brain areas can be observed in severely depressed patients. METHODS:
      The present study combined proton magnetic resonance spectroscopy (1H MRS, n=16;
      healthy controls n=27) and magnetoencephalography (MEG, n=17, controls n=18) of
      the left auditory cortex in severely depressed inpatients pre- and post
      successful antidepressive therapy. For MEG recordings, patients were stimulated
      with trains of 4 successive vowels or 4 sine tones, respectively. For each of the
      4 stimuli, the amplitude and latency of the N1m was calculated. As a measure of
      habituation the decrease of the individual amplitudes of the second, third and
      fourth N1m compared to the first N1m was calculated. RESULTS: Prior to therapy, a
      subset of patients presented clearly disturbed auditory processing to stimuli
      (missing of distinct N1m1 and subsequent habituation; 5 of 17 patients (vowels)
      and 9/17 (tones, respectively)). After treatment, compared to controls, a
      normalized habituation pattern was observed in all patients for vowels, but not
      for tones. In contrast, MRS revealed no significant differences between the
      metabolite concentrations of patients and healthy controls in both measurements.
      CONCLUSION: Depression may be accompanied by impaired auditory processing, which
      seems to improve with reduction in depressive symptoms. Auditory cortical
      dysfunction probably reflects only a part from more widespread aberrations of
      brain function occurring with severe mood disorder.

PMID- 16288923
TI  - Correlation of gene and protein structures in the FXYD family proteins.
AB  - The FXYD family proteins are auxiliary subunits of the Na,K-ATPase, expressed
      primarily in tissues that specialize in fluid or solute transport, or that are
      electrically excitable. These proteins range in size from about 60 to 160 amino
      acid residues, and share a core homology of 35 amino acid residues in and around
      a single transmembrane segment. Despite their relatively small sizes, they are
      all encoded by genes with six to nine small exons. We show that the helical
      secondary structures of three FXYD family members, FXYD1, FXYD3, and FXYD4,
      determined in micelles by NMR spectroscopy, reflect the structures of their
      corresponding genes. The coincidence of helical regions, and connecting segments,
      with the positions of intron-exon junctions in the genes, support the hypothesis
      that the FXYD proteins may have been assembled from discrete structural modules
      through exon shuffling.

PMID- 16288925
TI  - Chronic ethanol consumption alters cardiovascular functions in conscious rats.
AB  - Chronic ethanol intake and hypertension are related. In the present work, we
      investigated the effect of chronic ethanol (20% v/v) intake for 2, 6 and 10 weeks
      on basal arterial blood pressure, baroreflex and heart rate levels, as well as on
      the cardiovascular responses to the infusion of vasoactive agents in
      unanesthetized rats. Mild hypertension was observed after 2 weeks, 6 weeks or 10
      weeks of treatment. On the other hand, no changes were observed in heart rate
      after long-term ethanol intake. Similar baroreflex changes were observed in 2- or
      6-week ethanol-treated rats, and affected all parameters of baroreflex sigmoid
      curves, when compared to the control group. These changes were characterized by
      an enhanced baroreflex sympathetic component and a reduction in the baroreflex
      parasympathetic component. No differences in baroreflex parameters were observed
      in 10-week ethanol-treated animals. The pressor effects of i.v. phenylephrine
      were enhanced in 2-week ethanol-treated rats; not affected in 6-week treated
      animals and reduced in 10-week ethanol-treated rats, when compared to respective
      control and isocaloric groups. The hypotensive response to i.v. sodium
      nitroprusside (SNP) was enhanced at all different times of treatment, when
      compared to respective control and isocaloric groups. In conclusion, the present
      findings showed increased arterial pressure in the early phase of chronic ethanol
      consumption, which was consequent of rise in both systolic and diastolic
      pressures. Ethanol intake affected both the sympathetic and the parasympathetic
      components of the baroreflex. Vascular responsiveness to the pressor agent
      phenylephrine was initially enhanced and later on decreased during chronic
      ethanol intake. Vascular responsiveness to the depressor agent SNP was enhanced
      during chronic ethanol intake.

PMID- 16288926
TI  - The influence of lead and arsenite on the inhibition of human breast cancer MCF-7
      cell proliferation by American ginseng root (Panax quinquefolius L.).
AB  - American ginseng root (Panax quinquefolius) has a number of purported therapeutic
      effects, including inhibition of cancer cell proliferation. The ability of
      environmentally relevant heavy metals to alter ginseng effects on cancer cell
      growth was the subject of this study. A water extract of American ginseng root
      was applied alone or in combination with physiologically relevant doses of either
      lead (Pb) or arsenite to MCF-7 breast cancer cells in vitro and effects on cell
      proliferation were determined. Ginseng alone produced a significant dose
      dependent inhibition of MCF-7 cell proliferation starting at 0.5 mg ml(-1).
      Treatment of MCF-7 cells with 2.5 microM arsenite significantly decreased MCF-7
      cell proliferation (p < 0.01). When cells were treated with arsenite (1.25 or 2.5
      microM) in combination with ginseng extract (0.5 mg ml(-1)), there was an
      apparent synergistic inhibition of cell proliferation. Treatment of MCF-7 breast
      cancer cells with 50 microM Pb significantly decreased cell proliferation
      relative to control (p < 0.01), and concomitant ginseng and Pb treatment did not
      lead to a further decrease. These results suggest that contaminant heavy metals,
      some of which have been detected in ginseng root extracts or commercial ginseng
      preparations, may alter the biological activity of ginseng.

PMID- 16288927
TI  - The role of antagonism of NMDA receptor-mediated neurotransmission and inhibition
      of the dopamine reuptake in the neuroendocrine effects of phencyclidine.
AB  - Phencyclidine (PCP) activates the hypothalamo-pituitary-adrenal (HPA) axis and
      decreases plasma prolactin levels in the rat. PCP is a noncompetitive N-methyl-d
      aspartate (NMDA) receptor antagonist, but it also inhibits the reuptake of
      dopamine, serotonin and norepinephrine. The purpose of the present study was to
      utilize the PCP analogue N-[1-(2-thienyl)cyclohexyl]piperidine; (TCP), the potent
      dopamine reuptake inhibitor N-[1-(2-benzo(b)thiophenyl) cyclohexyl]piperidine;
      (BTCP) and the nonselective monoamine reuptake inhibitor cocaine as pharmacologic
      probes in order to determine the roles of noncompetitive NMDA receptor blockade
      and inhibition of dopamine reuptake in the neuroendocrine effects of PCP. PCP,
      TCP and cocaine increased plasma levels of adrenocorticotropin and
      corticosterone, but BTCP had no effect. In contrast, PCP, BTCP and cocaine
      decreased plasma prolactin, but TCP produced no such effect. The data suggest
      that mechanisms besides inhibition of dopamine reuptake are involved in the
      effects of PCP on the HPA axis, and the PCP-induced decrease in plasma prolactin
      is not a consequence of inhibition of NMDA receptor-mediated neurotransmission.

PMID- 16288928
TI  - Differences in the nitric oxide metabolism in streptozotocin-treated rats and
      children suffering from Type 1 diabetes.
AB  - The relationship between diabetes mellitus Type 1 and nitric oxide (NO) synthesis
      was studied in multiple low-dose streptozotocin (STZ)-treated rats and diabetic
      children. The aim of our experimental work was to test the effect of
      hyperglycemic state on the level of urinary stable NO end products and on the
      expression of inducible nitric oxide synthase (NOS II) in white blood cells
      (WBC). It was also studied whether the measurements of these parameters were
      suitable to predict the presence of early diabetes before its onset. The
      occurrence of insulitis in streptozotocin-treated rats could not be clearly
      demonstrated. Urinary nitrite plus nitrate level significantly increased both in
      diabetic rats and in children compared to controls. However, the increase of the
      activity and the expression of inducible NOS II were only observed in rat white
      blood cells and this effect was prevented by insulin treatment. In human samples,
      less than 25% of children showed elevated NOS II expression in white blood cells
      without any correlation to the level of urinary NO end products and glycated
      hemoglobin in blood. Correlation was found only between the activity and
      expression of NOS II in white blood cells of patients whose white blood cells
      were positive for the presence of NOS II. Measurement of urinary nitrite plus
      nitrate content as well as the determination of NOS II expression of white blood
      cells in an early phase of diabetes are not suitable predictors in humans
      probably due to the basic differences in the mechanism of streptozotocin-induced
      rat and spontaneous human Type 1 diabetes.

PMID- 16288929
TI  - Patterns of inorganic phosphate uptake in Cassiopea xamachana: a bioindicator
      species.
AB  - Nutrient levels in the nearshore waters of the Florida Keys have increased over
      the past few decades concomitant with a decline in the health of Florida's reef
      system. Phosphorus is a particular concern in the Florida Keys as it may be the
      limiting nutrient in nearshore waters. We demonstrate that the upside-down
      jellyfish, Cassiopea xamachana, decreases its rate of phosphate uptake following
      exposure to elevated levels of dissolved inorganic phosphate. We also show that
      this subsequent suppression of uptake rates persists for some time following
      exposure to elevated phosphates. Using these attributes, we experimentally
      investigated the use of C. xamachana as a bioindicator for dissolved inorganic
      phosphates in seawater. Our results show that these animals reveal comparative
      differences in environmental phosphates despite traditional testing methods
      yielding no detectable phosphates. We propose that C. xamachana is a bioindicator
      useful for integrating relevant information about phosphate availability in low
      nutrient environments.

PMID- 16288930
TI  - The neurotoxin 2'-NH2-MPTP degenerates serotonin axons and evokes increases in
      hippocampal BDNF.
AB  - 1-Methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP) causes long
      term depletions in cortical and hippocampal serotonin (5-HT) and norepinephrine
      (NE) that are accompanied by acute elevations in glial fibrillary acidic protein
      (GFAP) and argyrophilia. To further investigate the hypothesis that these changes
      are reflective of serotonergic and noradrenergic axonal degeneration, 2'-NH2-MPTP
      was administered to mice and innervation densities were determined
      immunocytochemically. Regional responses of the neurotrophin, brain-derived
      neurotrophic factor (BDNF), to putative damage were also assessed. Three days
      after 2'-NH2-MPTP, 5-HT axons exhibited a beaded, tortuous appearance indicative
      of ongoing degeneration. At 21 days, numbers of serotonin axons were
      significantly decreased, with the greatest axonal losses occurring in cortex and
      hippocampus. Serotonin axons in the amygdala were contrastingly spared long-term
      damage, as were 5-HT and NE cell bodies in the brain stem. BDNF protein levels
      were selectively increased in the hippocampus 3 days post-dose and returned to
      normal 21 days later. These results, in conjunction with previous findings,
      demonstrate that 2'-NH2-MPTP causes degeneration of serotonergic axons
      innervating the cortex and hippocampus on par with depletions in neurotransmitter
      levels. Moreover, damage to the hippocampus, a brain region important for
      learning and memory, and the modulation of anxiety and stress responsiveness,
      results in a transitory increase in BDNF.

PMID- 16288931
TI  - Mefloquine selectively increases asynchronous acetylcholine release from motor
      nerve terminals.
AB  - Effectiveness against chloroquine-resistant Plasmodia makes mefloquine a widely
      used antimalarial drug. However, mefloquine's neurologic effects offset this
      therapeutic advantage. Cellular actions which might contribute to the neurologic
      effects of mefloquine are not understood. Structural similarity to tacrine
      suggested that mefloquine might alter cholinergic synaptic transmission.
      Therefore, we examined mefloquine's effects at a model cholinergic synapse.
      Triangularis sterni nerve-muscle preparations were isolated from adult mice and
      examined with sharp electrode current clamp technique. Within 30 min of exposure
      to 10 microM mefloquine, miniature endplate potentials (mepps) occurred in
      summating bursts and their mean frequency increased 10-fold. The threshold
      concentration for the increase of mean mepp frequency was 0.6 microM mefloquine.
      Mefloquine continued to increase mean mepp frequency for preparations bathed in
      extracellular solution lacking Ca2+. In contrast, mefloquine no longer increased
      mean mepp frequency for preparations pre-treated with the intracellular Ca2+
      buffer BAPTA-AM. Although mefloquine disrupts a thapsigargin-sensitive neuronal
      Ca2+ store, pre-treatment with thapsigargin did not alter the mefloquine-induced
      alterations of mepps. Since mefloquine, like oligomycin, inhibits mitochondrial
      FOF1H+ ATP synthase we tested the interaction between these two chemicals. Like
      mefloquine, oligomycin induced bursts and increased mean frequency of mepps.
      Furthermore, pre-treatment with oligomycin precluded the mefloquine-induced
      alterations of asynchronous transmsitter release. These data suggest that
      mefloquine inhibits ATP production which increases the concentration of Ca2+
      within the cytosol of nerve terminals. This elevation of Ca2+ concentration
      selectively increases asynchronous transmitter release since 10 microM mefloquine
      did not alter stimulus-evoked transmsitter release.

PMID- 16288932
TI  - The cannabinoid receptor antagonist SR-141716A induces penile erection in male
      rats: involvement of paraventricular glutamic acid and nitric oxide.
AB  - The cannabinoid CB1 receptor antagonist SR141716A (0.5, 1 and 2 microg) induces
      penile erection when injected into the paraventricular nucleus of male rats. The
      pro-erectile effect of SR 141716A occurs concomitantly with an increase in the
      concentration of NO2- and NO3- in the paraventricular dialysate obtained by means
      of intracerebral microdialysis. Both penile erection and NO2- increase induced by
      SR 141716A were reduced by the prior injection into the PVN of the cannabinoid
      CB1 agonists WIN 55,212-2 (5 microg) or HU 210 (5 microg), given into the
      paraventricular nucleus at doses unable to induce penile erection or to modify
      NO2- concentration. SR 141716A responses were also reduced by nitro-L-arginine
      methylester (20 microg), a non-selective NO synthase inhibitor, S-methyl-L
      thiocitrulline (20 microg), a selective neuronal NO synthase inhibitor, the
      excitatory amino acid NMDA receptor antagonist dizocilpine ((+)MK 801) (1
      microg), or the GABAA receptor agonist muscimol (0.2 microg) injected into the
      PVN 15 min before SR 141716A. In contrast, the inducible NO synthase inhibitor L
      N(6)-(1-iminoethyl)lysine (20 microg), the GABAB receptor agonist baclofen (0.2
      microg), the mixed dopamine receptor antagonist cis-flupenthixol (10 microg), and
      the oxytocin receptor antagonist d(CH2)5Tyr(Me)-Orn8 -vasotocin (1 microg), were
      ineffective. Despite its inability to reduce penile erection and NO2- increase
      induced by SR 141716A when injected into the PVN, d(CH2)5Tyr(Me)-Orn8 -vasotocin
      (1 microg) reduced almost completely penile erection without reducing
      paraventricular NO2- increase when injected into the lateral ventricles 15 min
      before SR 141716A. The present results show that SR 141716 induces penile
      erection by a mechanism (possibly activation of excitatory amino acid
      neurotransmission), which causes the activation of neuronal NO synthase in
      paraventricular oxytocinergic neurons mediating penile erection.

PMID- 16288933
TI  - Chemotherapeutic efficacy of ascofuranone in Trypanosoma vivax-infected mice
      without glycerol.
AB  - Ascofuranone, an antibiotic isolated from Ascochyta visiae, showed trypanocidal
      activity in Trypanosoma vivax-infected mice. A single dose of 50 mg/kg
      ascofuranone effectively cured the mice without the help of glycerol. Repeated
      administrations of this drug further enhanced its chemotherapeutic effect. After
      two, three, and four consecutive days treatment, the doses needed to cure the
      infection decreased to 25, 12, and 6 mg/kg, so that the total doses administered
      were 50, 36 and 24 mg/kg, respectively. Ascofuranone (50 mg/kg) also had a
      prophylactic effect against T. vivax infection within the first two days after
      administration. This prophylactic activity diminished to 80% by day 3 and
      completely disappeared four days after administration. Of particular interest in
      this study was that ascofuranone had trypanocidal activity in T. vivax-infected
      mice in the absence of glycerol, whereas co-administration of glycerol or
      repeated administrations of this drug are needed for Trypanosoma brucei brucei
      infection. Our present results strongly suggest that ascofuranone is also an
      effective tool in chemotherapy against African trypanosomiasis in domestic
      animals.

PMID- 16288934
TI  - Circulating endothelial progenitor cells from healthy smokers exhibit impaired
      functional activities.
AB  - OBJECTIVE: Endothelial dysfunction is one of the earliest pathological effects of
      cigarette smoking. It has recently been suggested that endothelial progenitor
      cells (EPCs) could contribute to ongoing endothelial maintenance and repair.
      Accordingly, we tested the hypothesis that cigarette smoking is associated with
      EPC dysfunction. METHODS AND RESULTS: EPCs were isolated from the peripheral
      venous blood of 15 healthy smokers and 11 age-matched nonsmokers. The number of
      EPCs was significantly reduced in smokers versus control subjects (51.6+/-1.9
      versus 120.3+/-10.0 per power field, p<0.001). Moreover, the functional
      activities of EPCs isolated from smokers were severely compromised. First, the
      proliferative and migratory response of EPCs isolated from smokers were reduced
      by 75% and 19%, respectively (p<0.05). Second, EPCs from smokers showed an
      important decreased adherence to HUVECs that had been previously activated with
      tumor necrosis factor-alpha (TNF-alpha) (p<0.01). Finally, the participation of
      EPCs to tube formation in a matrigel assay was reduced by 38% in smokers versus
      control subjects (p<0.001). We found that EPCs from smokers had a significant
      reduction in the expression of the endothelial cell-specific markers (VE
      cadherin, KDR, and vWF). Moreover, ROS formation was significantly increased in
      EPCs from smokers, whereas the serum antioxidant and nitrite levels of smokers
      were reduced and correlated with impaired EPC number and functional activity.
      CONCLUSIONS: Cigarette smoking is associated with a reduced number of EPCs
      together with an important impairment of EPC differentiation and functional
      activities. Our results suggest that EPC dysfunction could contribute to impair
      blood vessel healing and growth in smokers.

PMID- 16288935
TI  - The V227A polymorphism at the PPARA locus is associated with serum lipid
      concentrations and modulates the association between dietary polyunsaturated
      fatty acid intake and serum high density lipoprotein concentrations in Chinese
      women.
AB  - Peroxisome proliferators activated receptor alpha (PPARalpha) regulates the
      transcription of several proteins involved in human lipoprotein metabolism. We
      screened the PPARA locus for polymorphisms in 20 unrelated subjects from each of
      three ethnic groups (Chinese, Malays and Asian Indians). Only the V227A
      polymorphism was observed. We genotyped 4248 subjects (2899 Chinese, 761 Malay
      and 588 Asian Indians) and found allele frequencies for the A227 allele of 0.04
      in Chinese, 0.006 in Malays and 0.003 in Asian Indians. We examined the
      associations between this polymorphism and serum lipid concentrations in Chinese.
      In women, but not in men, the presence of the A227 allele was associated with
      lower serum concentrations of total cholesterol [5.38mmol/l (95%CI: 5.22-5.54)
      versus 5.21mmol/l (95%CI: 4.99-5.43), p=0.047] and triglycerides [1.19mmol/l
      (95%CI: 1.10-1.28) versus 1.09mmol/l (95%CI: 0.98-1.21), p=0.048]. We also found
      that the V227A polymorphism modulates the association between dietary
      polyunsaturated fatty acid intake and serum high density lipoprotein
      concentration (p-value for interaction=0.049). Our findings implicate PPARalpha
      in the lipid lowering associated with diets high in PUFA and suggests that
      genetic variation at the PPARA locus may determine the lipid response to changes
      in PUFA intake.

PMID- 16288936
TI  - Age related differences in the immune response to vaccination and infection with
      Mycoplasma gallisepticum.
AB  - Several studies have suggested that there are age related differences in the
      responses of chickens to vaccination and infection with Mycoplasma gallisepticum,
      but there have not been any systematic comparisons of the responses of young
      birds to vaccination with those of birds the same age to infection. The aim of
      the studies described here was to examine the immune responses of chickens
      between 1 and 6 weeks of age to vaccination and to infection with M.
      gallisepticum. Birds under 4 weeks of age developed significantly more severe
      clinical signs after infection with virulent M. gallisepticum than birds that
      were 4 or 6-weeks old at the time of infection, with greater concentrations of M.
      gallisepticum in the trachea. Chickens younger than 4 weeks old at the age of
      vaccination were protected from clinical signs of disease after challenge and
      from development of more severe lesions in the trachea and air sacs, although
      this protective immunity was significantly less effective in controlling the
      replication of M. gallisepticum in the trachea. Examination of the subsets of
      lymphocytes infiltrating the tracheal mucosa did not detect any age related
      differences. Thus the ts-11 vaccine has been shown to be safe in birds between 1
      and 4 weeks of age and to be effective in preventing development of severe
      disease in them after challenge, even though birds of the same age were more
      susceptible to development of disease when infected with virulent M.
      gallisepticum.

PMID- 16288937
TI  - Impact of corticosteroids on the immune response to a MF59-adjuvanted influenza
      vaccine in elderly COPD-patients.
AB  - The influence of steroids on the antibody response to a MF59-adjuvanted influenza
      vaccine in elderly COPD patients has not been studied previously. In the
      influenza season 2001/02 (October-February) elderly COPD patients were recruited
      at 14 doctor's offices and our 250-bed hospital. Patients were stratified into
      three groups according to current treatment regimen: (a) > 10 mg of
      prednisolone/day (SS); (b) inhaled steroids (IS); (c) no steroid treatment
      (control group, CG). All patients were vaccinated with the MF59-adjuvanted
      influenza vaccine. Antibodies against the influenza strains A/H1N1, A/H3N2, and B
      were measured at baseline, 4 and 24 weeks after vaccination by hemagglutination
      inhibition (HI) assay. One-hundred and sixty-two patients completed the study (CG
      n = 42; IS n = 87; SS n = 33). Mean age was 71.3 years (range 60-89). Twenty-one
      percent of all patients reported local reactions; no serious adverse events were
      observed. Four weeks after vaccination, mean geometric HI titres (GMT) for
      A/H1N1, A/H3N and B increased significantly in all groups (p < or = 0.05). After
      24 weeks, GMTs to A/H1N1 and A/H3N2 returned to baseline, while GMTs to type B
      remained significantly higher than baseline in all groups. Significant
      differences between the groups as regards GMTs, seroconversion (56-89%) or
      seroprotection rates (64-93%) were not observed. Systemic steroids did not
      influence the antibody response towards the MF59-adjuvanted influenza vaccine. We
      found that the strains included in the vaccine showed varying long-term
      immunogenicity.

PMID- 16288938
TI  - Serum antibodies to putative proteinase maturation protein A in children with
      acute otitis media.
AB  - The pneumococcal genes encoding for the surface associated proteins have been
      proposed to be important for pneumococcal protein vaccine development. We cloned
      the full-length putative proteinase maturation protein A gene SP098l/ppmA (as
      published by Tettelin et al. in 2001) and produced the encoded protein in high
      levels in E. coli. The purified recombinant PpmA was used as an antigen in
      Western blotting to study systemic antibody responses to PpmA in animals and in
      children with acute otitis media (AOM). In children, the geometric mean titers of
      serum IgG antibodies against PpmA increased with age and differed significantly
      in relation to pneumococcal findings in middle ear fluid and/or nasopharyngeal
      aspirate. The serum IgG antibody titers against PpmA were low in children with
      Streptococcus pneumoniae cultured in the middle ear, and the highest in children
      with pneumococci in the nasopharynx, without them being found in the middle ear
      fluid. We conclude that PpmA is immunogenic in humans, and therefore an
      interesting antigen to study further in developing pneumococcal multicomponent
      protein vaccines.

PMID- 16288939
TI  - Evaluation of different plasmid DNA delivery systems for immunization against
      HER2/neu in a transgenic murine model of mammary carcinoma.
AB  - Studies of DNA vaccination against HER2/neu showed the effectiveness of
      immunization protocols in models of transplantable or spontaneous tumors; scarce
      information, however, has been provided to identify the procedure of DNA
      administration that more effectively contributes to the activation of immune
      system against spontaneously arising HER2/neu-positive tumors. We compared the
      effectiveness of different procedures of DNA vaccine delivery (intradermic
      injection (ID), gene gun (GG) delivery and intramuscular injection (IM) alone or
      with electroporation) in a murine transgenic model of mammary carcinoma
      overexpressing HER2/neu. We highlighted the role of DNA delivery system in the
      success of DNA vaccination showing that, among the analysed methods,
      intramuscular injection of the vaccine, particularly when associated to
      electroporation, elicits a better protection against HER2/neu spontaneous tumor
      development inducing antibody and cell-mediated immune responsiveness against
      HER2/neu and a Th1 polarization of the immune response.

PMID- 16288940
TI  - Re: Use of Dermabond in nail injuries.

PMID- 16288941
TI  - The unstable shoulder in arm elevation: a three-dimensional and electromyographic
      study in subjects with glenohumeral instability.
AB  - BACKGROUND: Although an altered scapulohumeral rhythm is believed to be related
      to some shoulder dysfunctions, there is scarce evidence on the scapulohumeral
      rhythm and shoulder muscle activation patterns in subjects with glenohumeral
      instability. METHODS: Six subjects with glenohumeral instability performed arm
      elevation in trials of 8 successive stationary positions. Kinematics were
      recorded on each stationary position using a 6 DOF electromagnetic tracking
      device. Scapular kinematics was analysed by comparison between recorded scapular
      angles and those estimated by a linear regression model of the scapulohumeral
      rhythm which served as standard for normality. Surface electromyographic activity
      was recorded from the upper and lower trapezius, serratus anterior and deltoid.
      FINDINGS: Differences in the scapulohumeral rhythm were observed between
      subjects. Significant differences were founded in scapular protraction and spinal
      tilt. No differences were found in scapular lateral-rotation in all subjects.
      Activity of the lower trapezius and serratus anterior seem to increase mostly
      during the second third of arm elevation. INTERPRETATION: In a particular angle
      of arm elevation, changes in scapular protraction and/or spinal tilt rotation
      could introduce changes on the alignment of the humeral head and the glenoid,
      predisposing/contributing to shoulder instability. These kinematics scapular
      changes are perhaps due to an inadequate muscular activity. RELEVANCE: The
      results of this study reinforce the relevance of the scapulohumeral rhythm
      assessment in the rehabilitation of patients with shoulder instability.

PMID- 16288942
TI  - A kinematical analysis of the shoulder after arthroplasty during a hair combing
      task.
AB  - BACKGROUND: After shoulder arthroplasty, post-operative Range of Motion is
      usually compromised. It is, however, unclear to what extent limitations in Range
      of Motion are related to functional outcome in terms of Activities of Daily
      Living. METHODS: The upper extremity motions of 13 patients (16 shoulders) and a
      control group (N = 24) during four Range of Motion tasks and Activities of Daily
      Living were measured using a six degree-of-freedom electromagnetic tracking
      device. Based on the results for the Activities of Daily Living task 'hair
      combing', the patient groups was divided into a group that could perform this
      task ('Able', N = 8, 10 shoulders) and a group that could not perform the task
      ('Unable', N = 6, six shoulders). RESULTS: Both patient groups showed
      considerable limitation in glenohumeral Range of Motion, when compared to
      controls, but between patient groups only axial rotation Range of Motion was
      different: the 'Able' group has a larger external rotational Range of Motion, but
      less internal rotation. During 'combing hair' the Able group appeared to
      successfully perform the task through a larger clavicular retraction.
      INTERPRETATION: The ability to perform, or not perform a task appeared to be
      related to a compensatory movement implementation by means of clavicular
      retraction. It is concluded that the functional outcome after arthroplasty is
      limited due to a lack of glenohumeral Range of Motion but that it is possible to
      compensate for this restriction.

PMID- 16288943
TI  - Effect of Achilles tendon loading on plantar fascia tension in the standing foot.
AB  - BACKGROUND: The plantar fascia, which is one of the major arch-supporting
      structures of the human foot, sustains high tensions during weight-bearing. A
      positive correlation between Achilles tendon loading and plantar fascia tension
      has been reported. Excessive stretching and tightness of the Achilles tendon are
      thought to be the risk factors of plantar fasciitis but their biomechanical
      effects on the plantar fascia have not been fully addressed. METHODS: A three
      dimensional finite element model of the human foot and ankle, incorporating
      geometrical and material nonlinearity, was employed to investigate the loading
      response of the plantar fascia in the standing foot with different magnitudes of
      Achilles tendon loading. FINDINGS: With the total ground reaction forces of one
      foot maintained at 350 N to represent half body weight, an increase in Achilles
      tendon load from (0-700 N) resulted in a general increase in total force and peak
      plantar pressure at the forefoot of up to about 250%. There was a lateral and
      anterior shift of the centre of pressure and a reduction in the arch height with
      an increasing Achilles tendon load as a result of the plantar flexion moment on
      the calcaneus. From the finite element predictions of simulated balanced
      standing, Achilles tendon forces of 75% of the total weight on the foot (350 N)
      were found to provide the closest match of the measured centre of pressure of the
      subject during balanced standing. Both the weight on the foot and Achilles tendon
      loading resulted in an increase in tension of the plantar fascia with the latter
      showing a two-times larger straining effect. INTERPRETATION: Increasing tension
      on the Achilles tendon is coupled with an increasing strain on the plantar
      fascia. Overstretching of the Achilles tendon resulting from intense muscle
      contraction and passive stretching of tight Achilles tendon are plausible
      mechanical factors for overstraining of the plantar fascia.

PMID- 16288944
TI  - Significance of ammonium compounds on nicotine exposure to cigarette smokers.
AB  - The tobacco industry publicly contends that ammonia compounds are solely used as
      tobacco additive for purposes of tobacco flavoring, process conditioning and
      reduction of its subjective harshness and irritation. However, neither objective
      scientific reports, nor the contents of a large number of internal tobacco
      company documents support this contention. The present review focuses on the
      hypothesis that addition of ammonium compounds to tobacco enhances global tobacco
      use due to smoke alkalization and enhanced free-nicotine nicotine exposure.
      Obviously, ammonia enhances the alkalinity of tobacco smoke. Consequently, the
      equilibrium shifts from non-volatile nicotine salts to the volatile free base
      that is more readily absorbed from the airways. The observed change in the
      kinetics of nicotine (i.e., shorter t(1/2) and higher c(max)) after ammoniation
      is, however, predominantly due to the higher concentration of nicotine in the
      smoke, rather than to an increase in the absorption rate of free-base nicotine in
      the respiratory tract. Although several findings support the hypothesis,
      additional studies are required and suggested to provide a proper, objective and
      independent scientific judgment about the effect of tobacco ammoniation on
      nicotine bioavailability. Scientific and public awareness of the effects of
      tobacco-specific ammonia compounds may stimulate global control, legislation and
      restriction of their use in cigarette manufacture.

PMID- 16288945
TI  - Biodegradation or metabolism of bisphenol A: from microorganisms to mammals.
AB  - Bisphenol A (BPA; 2,2-bis(4-hydroxyphenyl)propane; CAS Registry No. 80-05-7) is
      one of endocrine disruptors and is made by combining acetone and phenol. BPA can
      be metabolized by extensive organisms. In this review these BPA biodegradations
      or metabolisms by many organisms from microorganisms to mammals were referred.
      Though the metabolites of BPA can enhance estrogenicity or toxicity, generally,
      BPA metabolism by organisms leads to detoxication of BPA.

PMID- 16288946
TI  - Loss of basolateral invaginations in proximal tubules of cadmium-intoxicated rats
      is independent of microtubules and clathrin.
AB  - Experimental cadmium (Cd) nephrotoxicity after treating rats with CdCl(2) (2mg
      Cd/kg b.m./day) for 2 weeks (subchronic nephrotoxicity) or with Cd
      metallothionein (CdMT, a single dose of 0.4 mg Cd/kg b.m.) for a few hours (acute
      nephrotoxicity) is characterized by significant damage to cortical proximal
      tubules (PT) that results in reabsorptive and secretory defects. Most of the
      damage, studied so far, has been reported at the PT cell apical domain. This
      includes the loss of apical transporters and brush-border microvilli, and is
      considered to be the main cause of the kidney malfunction seen in this condition.
      However, in some studies the loss of basolateral (BL) invaginations and the
      activity of Na/K-ATPase in PT cells was also observed, but this "basolateral"
      aspect of intracellular Cd toxicity has been poorly investigated. In this report
      we induced subchronic and acute Cd nephrotoxicity in rats, and we studied the
      expression and intracellular distribution of microtubules and clathrin, and the
      abundance of Na/K-ATPase associated with BL invaginations in renal cortical
      tubules. Methods used were immunofluorescence microscopy, transmission and
      immunogold microscopy and immunoblotting of tissue homogenates and isolated total
      cell membranes. In both experimental models, in the cortical PT we demonstrated:
      (a) significantly damaged morphology of the cells, (b) fragmentation and
      depolymerization of microtubules, (c) loss of clathrin in the subapical domain
      and its relocation into vesicles scattered throughout the cytoplasm and (d) loss
      of BL invaginations and the associated Na/K-ATPase immunostaining. A similar loss
      of microtubules and redistribution of clathrin in the cortical PT was observed in
      rats treated with microtubule depolymerizing agent colchicine, but without any
      detectable loss of BL invaginations. We conclude that the loss of BL
      invaginations and the associated Na/K-ATPase in the cortical PT of Cd-intoxicated
      rats may contribute to the loss of PT function that characterizes Cd
      nephrotoxicity. This loss is accompanied by, but it is not dependent on
      perturbation of microtubule organization and loss of membrane-associated
      clathrin.

PMID- 16288947
TI  - Arsenic induced apoptosis in rat liver following repeated 60 days exposure.
AB  - BACKGROUND: Accumulation of the wide spread environmental toxin arsenic in liver
      results in hepatotoxcity. Exposure to arsenite and other arsenicals has been
      previously shown to induce apoptosis in certain tumor cell lines at low (1-3
      microM) concentration. AIM: The present study was focused to elucidate the role
      of free radicals in arsenic toxicity and to investigate the nature of in vivo
      sodium arsenite induced cell death in liver. METHODS: Male wistar rats were
      exposed to arsenite at three different doses of 0.05, 2.5 and 5mg/l for 60 days.
      Oxidative stress in liver was measured by estimating pro-oxidant and antioxidant
      activity in liver. Histopathological examination of liver was carried out by
      light and transmission electron microscopy. Analysis of DNA fragmentation by gel
      electrophoresis was used to identify apoptosis after the exposure. Terminal deoxy
      nucleotidyl transferase mediated dUTP Nick end-labeling (TUNEL) assay was used to
      qualify and quantify apoptosis. RESULTS: A significant increase in cytochrome
      P450 and lipid peroxidation accompanied with a significant alteration in the
      activity of many of the antioxidants was observed, all suggestive of arsenic
      induced oxidative stress. Histopathological examination under light and
      transmission electron microscope suggested a combination of ongoing necrosis and
      apoptosis. DNA-TUNEL showed an increase in apoptotic cells in liver. Agarose gel
      electrophoresis of DNA of hepatocytes resulted in a characteristic ladder
      pattern. CONCLUSION: Chronic arsenic administration induces a specific pattern of
      apoptosis called post-mitotic apoptosis.

PMID- 16288948
TI  - Stability of silorane dental monomers in aqueous systems.
AB  - Siloranes (silicon-based monomers with oxirane functionality) are investigated as
      matrix resins for new low shrinkage/stress dental composites. Compounds
      containing oxirane groups are known to be reactive with water, which could impart
      instability to the composite. OBJECTIVE: To test the stability of siloranes by
      measuring changes in the chemical structure of the oxirane group in aqueous
      environments. METHODS: Two siloranes (PH-SIL and TET-SIL) and their 1:1 mixture
      (SIL-MIX) were evaluated (n=2-3). Siloranes were mixed in aqueous solutions with
      and without 1% tetrahydrofuran (THF) containing either liver esterase or epoxide
      hydrolase at pH 7.4, or dilute HCl at pH 1.4. The stability of conventional
      dioxiranes 3,4-epoxycyclohexyl-methyl-3,4-epoxycyclohexane carboxylate (ECHM
      ECHC), and bisphenol A diglycidyl ether (BADGE) were also monitored under similar
      conditions. NMR was used to estimate the extent of reaction and give structural
      information about reaction products. RESULTS: Siloranes were found to be stable
      for 24h in all aqueous environments tested. In contrast, ECHM-ECHC reacted at pH
      1.4 to form species containing oxirane, ester, hydroxyl and carboxylic acid
      groups. Water hydrolyzed the ester group of ECHM-ECHC in the presence of liver
      esterase. In the presence of epoxide hydrolase, BADGE oxirane groups were
      hydrolyzed to diols, hydrolysis ranged from 0 to 34% depending on the aqueous
      environment. CONCLUSION: The stability and insolubility of siloranes in
      biological fluid simulants suggests that these may be more suitable for use in
      the oral environment than conventional oxirane-functional monomers.

PMID- 16288949
TI  - Effect of an antibacterial adhesive on the bond strength of three different
      luting resin composites.
AB  - OBJECTIVES: Effect of a dentin adhesive system containing antibacterial monomer
      MDPB (Clearfil Protect Bond) on the shear bond strength of all-ceramic-IPS
      Empress 2 restorations luted with three different dual-polymerizing systems
      (Variolink 2, RelyX ARC and Panavia F 2.0) to dentin was investigated. METHODS:
      One hundred and eight all-ceramic discs (2 x 3mm; IPS Empress 2) were fabricated
      and ultrasonically cleaned. The buccal surfaces of 108 non-carious extracted
      human premolars were flattened to expose dentin and subsequently polished with
      600-grit wet silicon carbide paper. Three dual-polymerizing luting systems had
      test groups and control groups consisting of 18 samples each. For the test groups
      Clearfil Protect Bond was applied to the exposed dentin surfaces. Control groups
      received the original bonding procedures of each adhesive system. After the all
      ceramic samples were luted to the teeth, thermocycling was performed 5000 times.
      Shear bond strengths were tested using Shimadzu Universal Testing Machine until
      failure. Analysis of fractured dentin surfaces were performed using Optical
      Microscope at x10 and x1000 magnifications and the images were analyzed with
      Image Analyzer. Data was analyzed with one-way ANOVA and Bonferroni test at a
      significance level of p<0.05. RESULTS: Mean shear bond strength data of the
      groups in MPa were; Variolink: 20.45+/-4.75, Variolink+Clearfil Protect
      Bond:29.32+/-2.37, RelyX ARC:18.82+/-3.19, RelyX ARC+Clearfil Protect
      Bond:25.58+/-4.05, Panavia F 2.0:17.11+/-2.98, Panavia F 2.0+Clearfil Protect
      Bond:24.40+/-7.46. Application of the antibacterial adhesive increased the shear
      bond strengths of all three dual-polymerizing systems to dentin (p=0.00). The
      surface analysis showed that most of the specimens showed the adhesive failure
      mode between the dentin and the composite luting agent interface. CONCLUSION: The
      antibacterial adhesive system Clearfil Protect Bond can be safely used to prevent
      the potential risk of complications resulting from bacterial activity regardless
      of affecting the bond strength of IPS Empress 2 restorations luted with the dual
      polimerizing systems used in this study.

PMID- 16288950
TI  - Electrophysiological correlates of error processing in borderline personality
      disorder.
AB  - The electrophysiological correlates of error processing were investigated in
      patients with borderline personality disorder (BPD) using event-related
      potentials (ERP). Twelve patients with BPD and 12 healthy controls were
      additionally rated with the Barratt impulsiveness scale (BIS-10). Participants
      performed a Go/Nogo task while a 64 channel EEG was recorded. Three ERP
      components were of special interest: error-related negativity (ERN)/error
      negativity (Ne), early error positivity (early Pe) reflecting automatic error
      processing, and the late Pe component which is thought to mirror the awareness of
      erroneous responses. We found smaller amplitudes of the ERN/Ne in patients with
      BPD compared to controls. Moreover, significant correlations with the BIS-10 non
      planning sub-score could be demonstrated for both the entire group and the
      patient group. No between-group differences were observed for the early and late
      Pe components. ERP measures appear to be a suitable tool to study clinical time
      courses in BPD.

PMID- 16288951
TI  - Mental fatigue, motivation and action monitoring.
AB  - In this study we examined whether the effects of mental fatigue on behaviour are
      due to reduced action monitoring as indexed by the error related negativity
      (Ne/ERN), N2 and contingent negative variation (CNV) event-related potential
      (ERP) components. Therefore, we had subjects perform a task, which required a
      high degree of action monitoring, continuously for 2h. In addition we tried to
      relate the observed behavioural and electrophysiological changes to motivational
      processes and individual differences. Changes in task performance due to fatigue
      were accompanied by a decrease in Ne/ERN and N2 amplitude, reflecting impaired
      action monitoring, as well as a decrease in CNV amplitude which reflects reduced
      response preparation with increasing fatigue. Increasing the motivational level
      of our subjects resulted in changes in behaviour and brain activity that were
      different for individual subjects. Subjects that increased their performance
      accuracy displayed an increase in Ne/ERN amplitude, while subjects that increased
      their response speed displayed an increase in CNV amplitude. We will discuss the
      effects prolonged task performance on the behavioural and physiological indices
      of action monitoring, as well as the relationship between fatigue, motivation and
      individual differences.

PMID- 16288952
TI  - Current treatment issues in female hyperprolactinaemia.
AB  - High prolactin levels can occur as a physiological condition in females who are
      pregnant or lactating. As a pathological condition, hyperprolactinaemia is
      associated with gonadal dysfunction, infertility and an increased risk of long
      term complications including osteoporosis. The most frequent cause of persistent
      hyperprolactinaemia is the presence of a micro- (<10mm diameter) or
      macroprolactinoma (>/=10mm). These pituitary tumours may produce an excessive
      amount of prolactin or disrupt the normal delivery of dopamine from the
      hypothalamus to the pituitary; prolactin secretion from the pituitary is
      inhibited by dopamine released from neurones in the hypothalamus. Medications
      including anti-psychotics can induce hyperprolactinaemia, while idiopathic
      hyperprolactinaemia accounts for 30-40% of cases. The prevalence of
      hyperprolactinaemia is difficult to establish as not all sufferers are
      symptomatic or concerned by their symptoms and may remain undiagnosed. Symptoms
      of hyperprolactinaemia include signs of hypogonadism, with oligomenorrhoea,
      amenorrhoea and galactorrhoea frequently observed. Pharmacological intervention
      should be considered the first line therapy and involves the use of dopamine
      agonists to reduce tumour size and prolactin levels. Bromocriptine has the
      longest history of use and is a well-established, inexpensive, safe and effective
      therapy option. However, bromocriptine requires multiple daily dosing and some
      patients are resistant or intolerant to this therapy. The two newer dopamine
      agonists, quinagolide and cabergoline, provide more effective and better
      tolerated treatments compared with bromocriptine and may offer effective
      therapies for bromocriptine-resistant or intolerant patients. Quinagolide can be
      used until pregnancy is confirmed and may result in improved compliance in
      females wishing to become pregnant. For patients with hyperprolactinaemia,
      pregnancy is safe and can frequently be beneficial, inducing a decrease in
      prolactin levels. There does not appear to be any increased risk of abortion,
      malformations or multiple births in pregnancies achieved with bromocriptine and
      this dopamine agonist can be used safely during pregnancy. Surgery should be
      considered only in certain circumstances, and for the majority of patients,
      dopamine agonists will be sufficient to alleviate symptoms and restore normal
      prolactin levels.

PMID- 16288953
TI  - Quantitative determination of the topological propensities of amyloidogenic
      peptides.
AB  - One of the interesting puzzles of amyloid beta-peptide of Alzheimer's disease
      (Abeta) is that it appears to polymerize into amyloid fibrils in a parallel beta
      sheet topology, while smaller subsets of the peptide produce anti-parallel beta
      sheets. In order to target potential weak points of amyloid fibrils in a rational
      drug design effort, it would be helpful to understand the forces that drive this
      change. We have designed two peptides CHQKLVFFAEDYNGKDEAFFVLKQHW and
      CHQKLVFFAEDYNGKHQKLVFFAEDW that join the significant amyloidogenic Abeta (14-23)
      sequence HQKLVFFAED in parallel and anti-parallel topologies, respectively.
      (Here, the word "parallel" refers only to residue sequence and not backbone
      topology). The N-termini of the hairpins were labeled with the fluorescent dye 5
      ((((2-iodoacetyl)amino)ethyl)amino)naphthalene-1-sulfonic acid (IAEDANS), forming
      a fluorescence energy transfer donor-acceptor pair with the C-terminus
      tryptophan. Circular dichroism results show that the anti-parallel hairpin adopts
      a beta-sheet conformation, while the parallel hairpin is disordered. Fluorescent
      Resonance Energy Transfer (FRET) results show that the distance between the donor
      and the acceptor is significantly shorter in the anti-parallel topology than in
      the parallel topology. The fluorescence intensity of anti-parallel hairpin also
      displays a linear concentration dependence, indicating that the FRET observed in
      the anti-parallel hairpin is from intra-molecular interactions. The results thus
      provide a quantitative estimate of the relative topological propensities of
      amyloidogenic peptides. Our FRET and CD results show that beta sheets involving
      the essential Abeta (14-23) fragment, strongly prefer the anti-parallel topology.
      Moreover, we provide a quantitative estimate of the relative preference for these
      two topologies. Such analysis can be repeated for larger subsets of Abeta to
      determine quantitatively the relative degree of preference for parallel/anti
      parallel topologies in given fragments of Abeta.

PMID- 16288955
TI  - Bead-like passage of chloride ions through ClC chloride channels.
AB  - The ClC chloride channels control the ionic composition of the cytoplasm and the
      volume of cells, and regulate electrical excitability. Recently, it has been
      proposed that prokaryotic ClC channels are H+-Cl- exchange transporter. Although
      X-ray and molecular dynamics (MD) studies of bacterial ClC channels have
      investigated the filter open-close and ion permeation mechanism of channels,
      details have remained unclear. We performed MD simulations of ClC channels
      involving H+, Na+, K+, or H3O+ in the intracellular region to elucidate the open
      close mechanism, and to clarify the role of H+ ion an H+-Cl- exchange
      transporter. Our simulations revealed that H+ and Na+ caused channel opening and
      the passage of Cl- ions. Na+ induced a bead-like string of Cl- -Na+-Cl--Na+-Cl-
      ions to form and permeate through ClC channels to the intracellular side with the
      widening of the channel pathway.

PMID- 16288954
TI  - The Na+ binding channel of human coagulation proteases: novel insights on the
      structure and allosteric modulation revealed by molecular surface analysis.
AB  - Thrombovascular diseases result from imbalanced haemostasis and comprise
      important health problems in the aging population worldwide. The activity of
      enzymes pertaining to the coagulation cascade of mammalians exhibit several
      control mechanisms in order to maintain a proper balance between bleeding and
      thrombosis. For instance, human coagulation serine proteases carrying a F225 or
      Y225 are allosteric modulated by the binding of Na+ in a water-filled channel
      connected to the primary specificity pocket (S1 subsite) of these enzymes. We
      have characterized the structure, topography and lipophilicity of this channel in
      the ligand-free fast (sodium-bound) and slow (sodium-free) forms of thrombin, in
      the sole available structure of activated protein C and in several structures of
      the coagulation factors VIIa, IXa and Xa, differing in the nature of the bound
      inhibitor and in the occupancy of exosite-I as well as the Ca2+ and Na+ binding
      sites. Opposite to thrombin, the aqueous channels in all other coagulation
      enzymes sheltering a Na+ binding site do not have an aperture on the enzyme
      surface opposite to the S1 subsite entrance. In these enzymes, the lack of the
      three-residue insertion in loop 1 (183-189) as found in thrombin allied to
      compensatory mutations in the positions 187-185 and 222 effects a constriction in
      the water-filled channel that ends up by segregating the ion binding site from
      the S1 subsite. We also disclosed major topographical changes on the thrombin's
      surface upon sodium release and transition to the slow form that culminate in the
      narrowing of the S1 subsite entrance and, strikingly, in the loss of
      communication between the primary specificity pocket and the exosite-I. Such
      observation is in accordance with existing experimental data demonstrating
      thermodynamic linkage between these distant regions on the thrombin surface.
      Conformational changes in F34, L40, R73 and T74 were the main responsible for
      this effect. A path by which these changes in the vicinity of exosite-I could be
      transmitted to the S1 subsite and, consequently, to the sodium binding site is
      proposed.

PMID- 16288956
TI  - Economic and financial analysis of harvesting and utilization of river reed in
      the Okavango Delta, Botswana.
AB  - The Okavango Delta, the largest Ramsar wetland site, is one of the most resource
      rich ecosystems in Botswana. A range of resources, including reeds, contribute in
      various ways to the well-being of many of the communities through subsistence and
      income generation. The economic value of reeds and other resources found in
      wetlands has been poorly understood, leading to the perception that wetlands are
      wastelands, and have little or no economic values. Such resources are therefore
      likely to receive lower priority in conservation when evaluated against other
      alternative activities. The aim of this research was to determine the benefit and
      financial and economic viability of harvesting river reed in the Okavango Delta.
      Primary data were collected through a structured questionnaire administered at
      three villages in the Okavango Delta. Secondary data were collected from existing
      literature. Financial and economic analysis was undertaken using static and
      financial models. Market prices were used to calculate the net income generated
      from the sale of harvested reed. The measurement criteria for static models were
      the annual net cash income, net annual economic benefit, and return on investment
      (ROI), while those under the dynamic models were the net present value (NPV),
      benefit cost ratio (BCR), and the net benefit investment (N/K) ratio. It was more
      financially profitable and economically viable to harvest and sell reeds at
      Shorobe village (a village relatively close to the District economic centre,
      Maun), than Shakawe or Etsha-13.

PMID- 16288957
TI  - A distance-based uncertainty analysis approach to multi-criteria decision
      analysis for water resource decision making.
AB  - The choice among alternative water supply sources is generally based on the
      fundamental objective of maximising the ratio of benefits to costs. There is,
      however, a need to consider sustainability, the environment and social
      implications in regional water resources planning, in addition to economics. In
      order to achieve this, multi-criteria decision analysis (MCDA) techniques can be
      used. Various sources of uncertainty exist in the application of MCDA methods,
      including the selection of the MCDA method, elicitation of criteria weights and
      assignment of criteria performance values. The focus of this paper is on the
      uncertainty in the criteria weights. Sensitivity analysis can be used to analyse
      the effects of uncertainties associated with the criteria weights. Two existing
      sensitivity methods are described in this paper and a new distance-based approach
      is proposed which overcomes limitations of these methods. The benefits of the
      proposed approach are the concurrent alteration of the criteria weights, the
      applicability of the method to a range of MCDA techniques and the identification
      of the most critical criteria weights. The existing and proposed methods are
      applied to three case studies and the results indicate that simultaneous
      consideration of the uncertainty in the criteria weights should be an integral
      part of the decision making process.

PMID- 16288958
TI  - Intrauterine Neospora caninum inoculation of heifers.
AB  - Here, we studied the potential of Neospora caninum tachyzoites to infect heifers
      when administered in utero by artificial insemination via contaminated semen.
      Eighteen primiparous cyclic heifers were hormonally synchronized and artificially
      inseminated. Nine of them, which were inseminated with semen containing 10(7)
      live N. caninum NC-1 isolate-tachyzoites, reacted with seroconversion and a
      specific IFN-gamma response. Moreover, N. caninum DNA was demonstrated by a
      nested-PCR in the blood of all nine heifers and in brain, lungs, liver and
      uterine horn of several of them. In contrast, nine heifers inseminated with
      tachyzoite-free semen developed no antibody or IFN-gamma responses, and no
      parasite DNA was detected in blood or organs. At necropsy, viable embryos were
      detected in one and six of the infected and non-infected heifers, respectively.
      No specific Neospora DNA was detected in any of the embryos. This study provides
      evidence that intrauterine inoculation via contaminated semen cause N. caninum
      infection in cattle.

PMID- 16288959
TI  - Sleep-related car crashes: risk perception and decision-making processes in young
      drivers.
AB  - The aim of the present study is to analyse factors affecting worries, coping
      strategies and decisions of young drivers regarding the risk of sleep-related car
      crashes. Furthermore, the study also analyses whether framing the same
      information about sleepiness in two different linguistic forms influences: (1)
      the evaluation of the level of risk associated to a specific level of drowsiness
      (Attribute Framing problem); (2) the willingness to enact strategies to "prevent"
      sleepiness before night-time driving (Goal Framing problem); (3) the choice
      between two different ways, both of equal expected efficacy, of lowering
      drowsiness (Risky decision-making Framing problem). Six hundred and ninety-five
      young drivers [(57.6% females, 42.4% males); mean age 20.85 years (S.D.=1.2)]
      answered questions on drive risk perception and sleepiness, on nocturnal driving
      experience and on the strategies to deal with driver sleepiness, responding to
      one of the two different versions of the framed problems. A sub-sample of 130
      participants completed the framed problems in both versions. The results show
      that experiences of sleep attacks and nocturnal driving frequency in the past 6
      months affect both risk perception and the preventive strategies adopted.
      Furthermore, the manipulation on two out of the three problems (attribute and
      risky decision-making frames) significantly affected the respondents' evaluation.

PMID- 16288960
TI  - Effect of inhaled nitric oxide on pulmonary vascular hyperpermeability in sheep
      following smoke inhalation.
AB  - Smoke inhalation increases mortality and morbidity in burn patients. We have
      reported that smoke inhalation increases lung lymph flow, an index of pulmonary
      transvascular fluid flux and decreases reflection coefficient, an index of
      microvascular permeability to protein. Nitric oxide has been reported to decrease
      microvascular permeability to protein. We hypothesize that inhaled nitric oxide
      decreases pulmonary microvascular hyperpermeability following smoke inhalation.
      Sheep were prepared for study with a chronic lung lymph fistula, Swan-Ganz, left
      atrial, and femoral arterial catheters. Occluders were placed on pulmonary veins
      to measure reflection coefficient. All animals were insufflated with 4 x 12
      breaths of cotton smoke. Sheep were randomly divided into two groups: NO
      (injured, treated with nitric oxide (40 ppm) inhalation, n=6) and control
      (injured, not treated, n=6). Nitric oxide inhalation was started 22 h after the
      insult. Control animals showed an increase in lung lymph flow, and lung water
      content. These changes were associated with marked increase in pulmonary
      microvascular resistance, pulmonary artery pressure, and decrease in reflection
      coefficient. Nitric oxide inhalation ameliorated the above-mentioned pathological
      changes. The results suggest that nitric oxide inhalation has potential for
      beneficial effect in the treatment of patients suffering from smoke inhalation.

PMID- 16288961
TI  - Postburn reconstruction of nipple-areola complex.
AB  - Reconstruction of burned nipple-areola complex is a significant problem. Many
      techniques are available. Most have been fraught with loss of nipple projection
      within 6 months. Local flaps seem to give better results. Drawbacks of these
      procedures in burned patients are excessive nipple flattening and difficulty in
      nipple reconstruction due to the low amount of subcutaneous fat and thin dermis
      because of tight scar. The modified star flap is a derivative of the skate design
      and includes the significant advantage of primary closure of the donor site. This
      article describes some modifications to the star flap, intended to decrease
      nipple flattening and improve flap stabilization, even in burned breasts. We
      performed seven nipple reconstructions in six young females who were victims of
      childhood burn injury. The final projection of nipples was 5 +/- 1mm. We think
      that our technique is a good alternative to previous ones and may be applied in
      all burned patients.

PMID- 16288962
TI  - Reconstruction of distal foot wounds with reverse first dorsal metatarsal artery
      flap.
AB  - Reconstruction of the distal portion of the foot has always represented a
      difficult problem in plastic surgery. We report a distally based dorsalis pedis
      island flap based on the first dorsal metatarsal artery, which has been
      successfully used to treat the distal portion of the foot in eight patients. The
      size of flaps ranged from 3 cm x 4 cm to 6 cm x 7 cm. In seven patients, the
      transferred flaps survived completely and in one flap there was superficial
      marginal necrosis. There was no donor site morbidity. All the patients had no
      difficulty in wearing shoes and were walking within 6 weeks. We suggest that the
      reverse first dorsal metatarsal artery flaps is a good option to reconstruct the
      wound of distal foot.

PMID- 16288963
TI  - On the use of prophylactic antibiotics in prevention of toxic shock syndrome.
AB  - No consensus exists among burn surgeons on the role of prophylactic antibiotics
      in prevention of toxic shock syndrome (TSS). We recently reported a series of 71
      children admitted with burns to our burn unit. By Centres for Disease Control
      (CDC) criteria, six of these were 'definite' and four 'probable' cases of TSS.
      Prior to this report, none of our patients were given prophylactic antibiotics.
      Thereafter, prophylactic therapy was included in the management of children
      admitted to the burns unit. The aim of this study was to assess whether
      prophylaxis with a one off single dose of systemic antibiotics prevented the
      occurrence of TSS. Data were collected prospectively between 1 January and 31
      December 2001, on all children admitted to the burns unit. Out of 50 children
      admitted to the burns unit, 39 received prophylactic antibiotics in the referring
      accident and emergency. Two of these became unwell but none fulfilled the CDC
      criteria. The remaining 11 patients were given antibiotics on admission out of
      which one child required direct admission to the intensive care unit with a
      working diagnosis of TSS. Retrospectively, his features did not conform to the
      CDC criteria. In conclusion, this study suggests that prophylaxis may prevent TSS
      in children.

PMID- 16288964
TI  - Severe burns following phototherapy with PUVA for vetiligo: a preventable
      complication that still happening.

PMID- 16288965
TI  - Following the fate of murine epidermal stem cells in a syngeneic dermal
      equivalent in vivo.
AB  - BACKGROUND: Stem cells in healthy epidermis have the capacity to produce
      structures, such as interfollicular epidermis, hair follicle, and sebaceous
      glands. Embryonic stem (ES) cells can be induced to differentiate into epidermal
      stem cells in vitro. These ESCs (epidermal or epidermoid stem cells derived from
      ES cells) have the potential to be an ideal replacement of those stem cells
      destroyed in severe injury, such as in deep and extensive burn. The aim of this
      study was to follow the fate of murine ESCs which were seeded in a syngeneic
      dermal equivalent and implanted into syngeneic recipient mice subcutaneously.
      METHODS: ES cells were induced in vitro to differentiate into ESCs. Stained with
      a fluorescent dye Hoechst 33342, these ESCs were seeded into a fibroblast
      collagen-gelatin sponge complex, functioning as a dermal equivalent model, and
      then implanted subcutaneously into 129/J mice, which were syngeneic to these stem
      cells. RESULTS: These ESCs were clearly visible in the implant by fluorescent
      microscopy 3 weeks or longer after implantation. These cells remained viable,
      differentiating into hair follicle-like structures, glandular structures, and
      gave rise to additional structures resembling native dermis. A number of markers
      were expressed in the differentiated structures, including CD29 (integrin beta1
      subunit) and cytokeratin 18 (CK18). No apparent rejection or severe side effects
      were observed at least during the 10 weeks following implantation. CONCLUSIONS:
      Now that ESCs can survive in vivo in this dermal equivalent model and
      differentiate into hair follicle-like structures as well as glandular structures,
      it is feasible to use these cells as seed cells in studies to fabricate dermal
      equivalents that have the potential to develop dermal appendages.

PMID- 16288967
TI  - Oral immune tolerance mediated by suppressor T cells may be responsible for the
      poorer prognosis of foregut cancers.
AB  - The poor prognosis of foregut cancers might, in part, be due to the immune
      tolerising effect of tumour antigens which are shed into the gastrointestinal
      tract and processed by the gut immune system. This would create a tumour specific
      tolerance without compromise of global immune functions. Experimental data shows
      that orally fed cancer tissue induces a non cross reactive attenuation of the
      cellular anti tumour host responses and confers a growth advantage specific to
      individual cancers. Although the cellular basis of such pro-tumourogenic
      responses has yet to be established, it is likely, based on studies of oral
      tolerance mechanisms, that recruitment of immune suppressive T cells (T(regs))
      may be responsible. Abrogation of oral immune tolerance to the tumour by immune
      based therapy could represent a significant advance in the management of upper
      gastrointestinal cancers.

PMID- 16288966
TI  - Dissociation-independent selection of high-affinity anti-hapten phage antibodies
      using cleavable biotin-conjugated haptens.
AB  - The engineering of hapten-specific antibodies with affinity constant higher (K(a)
      values >10(10)M(-1)) than those of conventional antibodies promises hapten
      immunoassays exhibiting sub-femtomole range sensitivity, based on the
      conventional competitive assay principle. Here we report a simple method to
      select phage particles displaying anti-hapten antibody fragments with
      exceptionally high affinity. 11-Deoxycortisol (11-DC), selected as a model target
      hapten, was covalently conjugated to biotin via a spacer that included a
      reductively cleavable disulfide bond. Phage particles displaying high-affinity,
      single-chain Fv fragments (scFvs) specific for 11-DC (K(a)1.3 x 10(10)M(-1)) were
      incubated with the "cleavable biotin"-conjugated 11-DC, and the resulting
      complexes was captured on immobilized NeutrAvidin. Mild reductive conditions that
      did not decrease phage infectivity easily cleaved the disulfide bond, allowing
      the recovery of target phage particles; this process is fully independent of the
      dissociation of the antigen-antibody interaction. Five serial rounds of selection
      enabled the isolation and enrichment of the anti-11-DC phage (specific phage
      ratio >90%) from among a 100,000-fold excess of nonspecific phage particles. This
      method will be applicable for selection of extra-high-affinity phage antibodies
      against a wide variety of haptens.

PMID- 16288968
TI  - Using ice cream headache to help physicians experience the pain of and empathize
      with cluster headache patients.

PMID- 16288969
TI  - The egg-sharing model for human therapeutic cloning research: managing donor
      selection criteria, the proportion of shared oocytes allocated to research, and
      amount of financial subsidy given to the donor.
AB  - Recent advances in human therapeutic cloning made by Hwang and colleagues have
      opened up new avenues of therapy for various human diseases. However, the major
      bottleneck of this new technology is the severe shortage of human donor oocytes.
      Egg-sharing in return for subsidized fertility treatment has been suggested as an
      ethically justifiable and practical solution to overcome the shortage of donor
      oocytes for therapeutic cloning. Because the utilization of shared oocytes in
      therapeutic cloning research does not result in any therapeutic benefit to a
      second party, this would necessitate a different management strategy compared to
      their use for the assisted conception of infertile women who are unable to
      produce any oocytes of their own. It is proposed that the pool of prospective egg
      sharers in therapeutic cloning research be limited only to younger women (below
      30 years of age) with indications for either male partner sub-fertility or tubal
      blockage. With regards to the proportion of the shared gametes being allocated to
      research, a threshold number of retrieved oocytes should be set that if not
      exceeded, would result in the patient being automatically removed from the egg
      sharing scheme. Any excess supernumerary oocyte above this threshold number can
      be contributed to science, and allocation should be done in a randomized manner.
      Perhaps, a total of 10 retrieved oocytes from the patient may be considered a
      suitable threshold, since the chances of conception are unlikely to be impaired.
      With regards to the amount of subsidy being given to the patient, it is suggested
      that the proportion of financial subsidy should be equal to the proportion of the
      patient's oocytes being allocated to research. No doubt, the promise of future
      therapeutic benefit may be offered to the patient instead of financial subsidy.
      However, this is ethically controversial because therapeutic cloning has not yet
      been demonstrated to be a viable model of clinical therapy and any promises made
      to the patient might turn out to be illusionary. Hence, it is proposed that a
      tangible financial subsidy on the medical fees might be the better option for the
      patient's welfare.

PMID- 16288970
TI  - Active site structure and catalytic mechanisms of human peroxidases.
AB  - Myeloperoxidase (MPO), eosinophil peroxidase, lactoperoxidase, and thyroid
      peroxidase are heme-containing oxidoreductases (EC 1.7.1.11), which bind ligands
      and/or undergo a series of redox reactions. Though sharing functional and
      structural homology, reflecting their phylogenetic origin, differences are
      observed regarding their spectral features, substrate specificities, redox
      properties, and kinetics of interconversion of the relevant redox intermediates
      ferric and ferrous peroxidase, compound I, compound II, and compound III.
      Depending on substrate availability, these heme enzymes path through the
      halogenation cycle and/or the peroxidase cycle and/or act as poor (pseudo
      )catalases. Based on the published crystal structures of free MPO and its
      complexes with cyanide, bromide and thiocyanate as well as on sequence analysis
      and modeling, we critically discuss structure-function relationships. This
      analysis highlights similarities and distinguishing features within the mammalian
      peroxidases and intents to provide the molecular and enzymatic basis to
      understand the prominent role of these heme enzymes in host defense against
      infection, hormone biosynthesis, and pathogenesis.

PMID- 16288971
TI  - Quantitative ultrasound imaging of spontaneous repair of porcine cartilage.
AB  - OBJECTIVE: Arthroscopy offers qualitative means to evaluate the surface of
      articular cartilage. However, possible degeneration of the deep cartilage and
      subchondral bone remains undetected. High frequency ultrasound imaging is an
      advanced cartilage evaluation method which is conceivable to arthroscopic use and
      brings diagnostic information also from deeper cartilage and subchondral bone.
      DESIGN: In this study, we characterized spontaneous repair of porcine cartilage
      in situ with quantitative 2D-ultrasound imaging. At the age of 7-8 months, a
      cartilage lesion (diameter 6mm, not penetrating into subchondral bone) was
      created on the lateral facet of the right femoral trochlea (n=8). The animals
      were sacrificed 3 months after the surgery. The lesion site, adjacent cartilage
      and the corresponding control area at the contralateral (left) knee were imaged
      in situ with 20 MHz ultrasound. Ultrasound reflection coefficients were
      determined from the cartilage surface (R) and from the cartilage-bone interface
      (R(bone)). Microtopography of the articular surface was quantified by calculating
      ultrasound roughness index (URI) parameter from the ultrasonically determined
      surface profile. RESULTS: Lesion site was spontaneously filled with visually
      cartilage-like soft tissue with smooth surface. However, ultrasonic images and
      histological analyses revealed erosion of subchondral bone under the lesion site.
      Ultrasound reflection (R) at the surface of the spontaneously repaired tissue was
      significantly lower (-73.5+/-7.6%, P<0.05) than at the surface of intact
      cartilage. R(bone) was lowest at the lesion site. The surface roughness of
      spontaneously repaired cartilage was significantly higher than that of the intact
      tissue (44.0+/-26.0 microm vs 7.5+/-2.3 microm, P<0.05). CONCLUSIONS:
      Quantitative ultrasound parameters offered diagnostic information revealing
      impaired structural integrity of the spontaneously repaired porcine cartilage and
      subchondral bone. These changes are not detectable by traditional arthroscopic
      means.

PMID- 16288973
TI  - Effect of salt concentration on membrane lysis pressure.
AB  - Cell membranes are capable of withstanding significant osmotic stress, the exact
      amount of which varies with the lipid composition. In this paper, we examine the
      effect that salt concentration has on the lysis pressure of membranes containing
      anionic lipids. Vesicles containing varying amounts of phosphatidylcholine and
      phosphatidylglycerol were osmotically stressed using NaCl as the osmolyte. The
      lysis pressure was observed to vary linearly with the Debye screening length and
      the extent of the variation was linear with anionic lipid content. The
      implications these results have for cells that frequently encounter low solute
      environments are discussed.

PMID- 16288972
TI  - Sodium-dependent glucose transporter reduces peroxynitrite and cell injury caused
      by cisplatin in renal tubular epithelial cells.
AB  - Cisplatin causes nephropathy accompanied by two types of cell death, necrosis and
      apoptosis, according to its dosage. The mechanisms of necrosis are still unclear.
      In this study, we examined how high doses of cisplatin induce cell injury and
      whether a high affinity sodium-dependent glucose transporter (SGLT1) has a
      cytoprotective function in renal epithelial LLC-PK(1) cells. Cisplatin decreased
      in transepithelial electrical resistance (TER) and increased in the number of
      necrotic dead cells in a time dependent manner. Phloridzin, a potent SGLT1
      inhibitor, enhanced both TER decrease and increase of necrotic dead cells caused
      by cisplatin. Cisplatin increased in the intracellular nitric oxide, superoxide
      anion and peroxynitrite productions. Phloridzin enhanced the peroxynitrite
      production caused by cisplatin. The intracellular diffusion of ZO-1 and TER
      decrease caused by cisplatin were inhibited by N-nitro-l-arginine methyl ester, a
      nitric oxide synthase inhibitor. Protein kinase C was not involved in the
      cisplatin-induced injury. 5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrinato
      iron (III) and reduced glutathione, peroxynitrite scavengers, inhibited the
      cisplatin-induced ZO-1 diffusion, TER decrease, and increase of necrotic dead
      cells. These results suggest that peroxynitrite is a key mediator in the
      nephrotoxicity caused by high doses of cisplatin. SGLT1 endogenously carries out
      the cytoprotective function by the reduction of peroxynitrite production.

PMID- 16288974
TI  - Effects of repeated in vivo inhalant nitrite exposure on gene expression in mouse
      liver and lungs.
AB  - Exposure to inhalant organic nitrites (drugs of abuse commonly known as
      "poppers") has been reported to enhance tumor growth in mice, but the mechanism
      is not fully defined. This study examined the effect of repeated in vivo nitrite
      exposures on gene expression in the mouse liver and lungs using a gene array
      panel of 94 cancer- and angiogenesis-related genes. Using 2-fold change as a
      threshold criterion, repeated nitrite exposure was found to alter the expression
      of 65 and 23 genes in the liver and lungs, respectively. Six genes were
      significantly upregulated (p<or=0.05), viz., those encoding VEGF, VEGFD (vascular
      endothelial growth factor A and D, respectively) in the lungs and FGF1, FGF4
      (fibroblast growth factor 1 and 4, respectively), Hsp70 (heat shock 70kDa protein
      4), and PF4 (platelet factor 4) in the liver. mRNA encoding HO-1 (heme oxygenase
      1) and Smad7 were marginally (p=0.057) stimulated in the liver. Follow-up studies
      in the liver revealed significant nitrite-induced expression of VEGF protein and
      mRNA. Immuno-staining of liver slices revealed that the increased hepatic VEGF
      expression resided mainly in hepatocytes. Stimulation of hepatic VEGF expression
      by ISBN was not different in endothelial nitric oxide synthase (eNOS) knockout
      vs. wild-type mice. In conclusion, multiple exposures to inhalant nitrite
      appeared to cause alteration in the expression of a number of genes relating to
      cancer and angiogenesis, including VEGF. eNOS presence did not appear to be
      essential for nitrite-induced VEGF expression. These studies demonstrate that in
      vivo exposure to inhalant nitrites results in changes in the angiogenesis
      cascade.

PMID- 16288975
TI  - Inhibition by nitric oxide of cytochrome P450 4A activity contributes to
      endotoxin-induced hypotension in rats.
AB  - Nitric oxide (NO) production during endotoxemia is associated with decreased
      total CYP content, CYP 1A1/2, 2B1/2, 2C6, 2C11, 3A1, and 3A2 mRNA, protein
      expression or activity which is prevented by NO synthase (NOS) inhibitors in
      rats. This study was conducted to determine if endotoxin-induced hypotension
      caused by NO production is mediated by inhibition of renal CYP 4A protein
      expression and activity. In conscious male Sprague-Dawley rats, endotoxin (10
      mg/kg, ip) reduced mean arterial pressure (MAP), increased serum and renal
      nitrite levels, and inducible NOS (iNOS), and decreased renal CYP 4A1/A3 protein
      and CYP 4A activity. The selective iNOS inhibitor 1,3-PBIT (10 mg/kg, ip; 1h
      after endotoxin) prevented endotoxin-induced decrease in MAP, renal CYP 4A1/A3
      protein level and CYP 4A activity and increase in systemic and renal nitrite
      production. The selective constitutive NOS (cNOS) inhibitor N(G)-nitro-L-arginine
      (L-NNA; 20 mg/kg, ip; 1 h after endotoxin) partially attenuated endotoxin-induced
      decrease in MAP. The selective CYP 4A inhibitor, aminobenzotriazole (50 mg/kg,
      ip; 1 h after endotoxin) diminished CYP 4A1/A3 protein level and CYP 4A activity.
      Aminobenzotriazole did not alter the endotoxin-induced decrease in MAP, but it
      reversed the effect of 1,3-PBIT in preventing endotoxin-induced fall in MAP and
      CYP 4A activity. These data suggest that the endotoxemia-induced increase in NO
      production primarily via iNOS suppresses renal CYP 4A expression and activity,
      and inhibition of iNOS with 1,3-PBIT restores renal CYP 4A protein and activity
      and MAP presumably due to increased production of arachidonic acid metabolites
      derived from CYP 4A.

PMID- 16288976
TI  - A novel lignan composition from Cedrus deodara induces apoptosis and early nitric
      oxide generation in human leukemia Molt-4 and HL-60 cells.
AB  - AP9-cd, a standardized lignan composition from Cedrus deodara consisting of (-)
      wikstromal, (-)-matairesinol, and dibenzyl butyrolactol, showed cytotoxicity in
      several human cancer cell lines reported earlier. An attempt was made in this
      study to investigate the mechanism of cell death in human leukemia Molt-4 and HL
      60 cells. It inhibited Molt-4 cell proliferation with 48-h IC(50) of
      approximately 15 microg/ml, increased sub-G0 cell fraction with no mitotic block,
      produced apoptotic bodies and induced DNA ladder formation. Flow cytometric
      analysis of annexinV-FITC/PI-stained cells showed time-related increase in
      apoptosis and post-apoptotic necrosis. All these biological end-points indicated
      cell death by apoptosis. Further, initial events involved massive nitric oxide
      (NO) formation within 4 h with subsequent late appearance of peroxides in cells;
      measured by flow cytometry using specific fluorescent probes. Persistently high
      levels of NO and peroxide appeared to decrease mitochondrial membrane potential
      (Psi(mt)) which was recovered by cyclosporin A in Molt-4 cells. AP9-cd caused 2
      fold activation of caspase-3 in Molt-4 and 5-fold activation in HL-60 cells. Also
      caspases-8 and -9 were activated in HL-60 cells. Ascorbate suppressed the
      enhanced caspases activities indicating a pro-oxidant effect of AP9-cd. Further,
      caspase-3 activation correlated with NO generation that was partially impaired by
      nitric oxide synthase (NOS) inhibitors and ascorbate suggesting a role of pro
      oxidant species in caspase-3 activation. AP9-cd produced no cytotoxicity in
      primary rat hepatocyte culture at the concentrations used. The studies indicated
      that AP9-cd mediated early NO formation leads to caspases activation, peroxide
      generation, and mitochondrial depolarization which may be responsible for
      mitochondrial-dependent and -independent apoptotic pathways involved in the
      killing of leukemia cells by AP9-cd.

PMID- 16288977
TI  - Phorbol ester mediated activation of inducible nitric oxide synthase results in
      platelet profilin nitration.
AB  - Nitric oxide is an important precursor for peroxynitrite production under in vivo
      conditions leading to cell injury and cell death. In platelets, a number of
      cytosolic and actin binding proteins were shown to be nitrated [K.M. Naseem, S.Y.
      Low, M. Sabetkar, N.J. Bradley, J. Khan, M. Jacobs, K.R. Bruckdorfer, The
      nitration of platelet cytosolic proteins during agonist-induced activation of
      platelets. FEBS Lett. 473 (1) (2000) 199-122 and M. Sabetkar, S.Y. Low, K.M.
      Naseem, K.R. Bruckdorfer, The nitration of proteins in platelets: significance in
      platelet function, Free Radic. Biol. Med. 33 (6) (2002) 728-736]. We investigated
      the possible mechanism that regulates profilin (an actin binding protein)
      nitration in platelets. Activation of bovine platelets with arachidonic acid,
      thrombin, and phorbol 12,13-dibutyrate resulted in nitration of profilin on
      tyrosine residue. In vivo profilin nitration showed a four- and eight-fold
      increase in the presence of thrombin and phorbol 12,13-dibutyrate, respectively.
      Analysis of nitroprofilin levels in the presence of NOS inhibitors (1400W and
      EGTA), indicated that profilin nitration in phorbol 12,13-dibutyrate treated
      platelets is mediated by inducible nitric oxide synthase. Phorbol ester treated
      platelets exhibited higher levels by inducible nitric oxide synthase (491% over
      control), while total nitric oxide synthase activity increased by 5% over
      control. Higher levels of peroxynitrite in platelets treated with phorbol 12,13
      dibutyrate indicated that profilin nitration is mediated by peroxynitrite.
      Increase in phosphatidylinositol 3-kinase (PI 3-kinase) activity in platelets
      treated with thrombin and phorbol 12,13-dibutyrate indicates that nitration of
      platelet profilin could be mediated by PI 3-kinase. A decrease in the level of
      nitroprofilin in PDBu treated platelets in the presence of inducible nitric oxide
      synthase inhibitor, 1400W, was observed suggesting that profilin nitration is
      mediated by PI 3-kinase dependent activation of inducible nitric oxide synthase.

PMID- 16288978
TI  - Transmission of social anxiety from mother to infant: an experimental study using
      a social referencing paradigm.
AB  - In this experiment we investigated the impact of indirect expressions of maternal
      social anxiety on infant interactions with a stranger. A social referencing
      paradigm was used in which infants first observed their mothers interacting with
      a stranger and then interacted with the stranger themselves. Mothers made no
      direct communicative gestures to the infant concerning the stranger throughout
      the procedure. There were two experimental conditions experienced by all mother
      infant pairs (N = 24; 12 boys)-non-anxious and socially anxious-and there were
      two male strangers. Infants were between 12 and 14 months (M = 12.8, SD = .76).
      Order of condition and stranger presentation were counter-balanced. Before
      testing, mothers, none of whom were significantly socially anxious, were trained
      to behave in a non-anxious and a socially anxious manner on the basis of clinical
      and empirical descriptions of social phobia. The results showed that, compared to
      their responses following their mothers interacting normally with a stranger,
      following a socially anxious mother-stranger interaction, infants were
      significantly more fearful and avoidant with the stranger. Infant-stranger
      avoidance was further modified by infant temperament; high fear infants were more
      avoidant in the socially anxious condition than low-fear infants. We discuss
      these findings in light of the possible mechanisms underpinning infant affective
      and behavioral responsiveness.

PMID- 16288979
TI  - Adsorption and diffusion of benzene in the nanoporous catalysts FAU, ZSM-5 and
      MCM-22: a molecular dynamics study.
AB  - Molecular dynamics (MD) simulations of benzene in siliceous zeolites (FAU, ZSM-5,
      and MCM-22) were performed at loadings of 1, 2, 4, 8, and 16 molecules per
      supercell. The potential energy functions for these simulations were constructed
      in a semi-empirical way from existing potentials and experimental energetic data.
      The MD simulations were employed to analyze the dynamic properties of the benzene
      zeolite systems. The adsorption energies of benzene/siliceous zeolite complexes
      increase with increasing loading number, due to the intermolecular attraction
      between benzene molecules. The self-diffusion coefficient of benzene in siliceous
      zeolites decreases with increasing loading due to the steric hindrance between
      the sorbates passing each other. From the zeolite-benzene radial distribution
      functions it was found that the benzene molecules are relatively far from each
      other, about 5.2A for siliceous FAU, 5.2A for siliceous ZSM-5, and 4.8A for
      siliceous MCM-22. In the case of FAU, the benzene molecules prefer to be adsorbed
      parallel to the surface of the sodalite cage above the six-membered-ring. In ZSM
      5, we found a T-structure of the benzene molecules at loadings 2, 4, and 8
      molecules per supercell. At loadings of 16 molecules per supercell, the molecules
      are lined up along the straight channel and their movement is highly correlated.
      For MCM-22 we found adjacent benzene molecules at a loading of 4 molecules with
      an orientation similar to the stacked conformation of benzene dimer in the gas
      phase.

PMID- 16288980
TI  - Unveiling hidden features of orphan nuclear receptors: the case of the small
      heterodimer partner (SHP).
AB  - The small heterodimer partner (SHP) is an atypical nuclear receptor lacking the N
      terminal ligand-independent activation domain and the DNA binding domain. SHP
      acts as transcriptional inhibitor of a large set of nuclear receptors, among
      which ER, AR, CAR, RXR, GR, LXR and ERRgamma. The repression mechanism of SHP
      involves several actions including competition with coactivators binding on the
      AF-2 of nuclear receptors and recruitment of transcriptional inhibitors such as
      EID-1. The investigation of the structure and repression mechanism of SHP is a
      challenging task for a full understanding of nuclear receptor interaction
      pathways and functions. So far, mutational analyses in multiple populations
      identified loss of function mutants of SHP gene involved in mild obesity,
      increased birth weight and insulin levels. Furthermore, experimental mutagenesis
      has been exploited to characterize the interactions between SHP and the
      transcriptional inhibitor EID-1. With the aim of gaining insight into the
      structural basis of SHP repression mechanism, we modelled SHP and EID-1
      structures. Docking experiments were carried out to identify the EID-1 binding
      surface on SHP structure. The results obtained in this study allow for the first
      time a unique interpretation of many experimental data available from the
      published literature. In addition, a fascinating hypothesis raises from the
      inspection of the proposed SHP structure: the presence of a potential unexpected
      ligand binding site, supported by recently available experimental data that may
      represent a breakthrough in the design and development of synthetic modulators of
      SHP functions.

PMID- 16288981
TI  - OCTN3 is a mammalian peroxisomal membrane carnitine transporter.
AB  - Carnitine is a zwitterion essential for the beta-oxidation of fatty acids. The
      role of the carnitine system is to maintain homeostasis in the acyl-CoA pools of
      the cell, keeping the acyl-CoA/CoA pool constant even under conditions of very
      high acyl-CoA turnover, thereby providing cells with a critical source of free
      CoA. Carnitine derivatives can be moved across intracellular barriers providing a
      shuttle mechanism between mitochondria, peroxisomes, and microsomes. We now
      demonstrate expression and colocalization of mOctn3, the intermediate-affinity
      carnitine transporter (Km 20 microM), and catalase in murine liver peroxisomes by
      TEM using immunogold labelled anti-mOctn3 and anti-catalase antibodies. We
      further demonstrate expression of hOCTN3 in control human cultured skin
      fibroblasts both by Western blotting and immunostaining analysis using our
      specific anti-mOctn3 antibody. In contrast with two peroxisomal biogenesis
      disorders, we show reduced expression of hOCTN3 in human PEX 1 deficient
      Zellweger fibroblasts in which the uptake of peroxisomal matrix enzymes is
      impaired but the biosynthesis of peroxisomal membrane proteins is normal, versus
      a complete absence of hOCTN3 in human PEX 19 deficient Zellweger fibroblasts in
      which both the uptake of peroxisomal matrix enzymes as well as peroxisomal
      membranes are deficient. This supports the localization of hOCTN3 to the
      peroxisomal membrane. Given the impermeability of the peroxisomal membrane and
      the key role of carnitine in the transport of different chain-shortened products
      out of peroxisomes, there appears to be a critical need for the intermediate
      affinity carnitine/organic cation transporter, OCTN3, on peroxisomal membranes
      now shown to be expressed in both human and murine peroxisomes. This Octn3
      localization is in keeping with the essential role of carnitine in peroxisomal
      lipid metabolism.

PMID- 16288982
TI  - BmCbZ, an insect-specific factor featuring a composite DNA-binding domain,
      interacts with BmC/EBPgamma.
AB  - A novel factor featuring a composite AT hook/basic region-leucine zipper DNA
      binding domain was isolated from Bombyx mori follicular cells. Screening of EST
      databases derived from a variety of metazoans revealed the exclusive presence of
      BmCbZ homologues in insect species. BmCbZ characteristic features and gene
      organization are discussed, in comparison to other known bZIP factors. We
      concordantly propose that this factor establishes a new insect-specific bZIP
      family. We further present the isolation of the silkmoth homologue of mammalian
      C/EBPgamma, BmC/EBPgamma, and in vitro evidence for its interaction with BmCbZ.
      The formation of a BmCbZ-BmC/EBPgamma heterodimer is a prerequisite for binding
      to specific C/EBP recognition sites on chorion gene promoters, most probably via
      both major and minor groove interactions.

PMID- 16288983
TI  - IL-6 modulates hepatocyte proliferation via induction of HGF/p21cip1: regulation
      by SOCS3.
AB  - The precise role of IL-6 in liver regeneration and hepatocyte proliferation is
      controversial and the role of SOCS3 in liver regeneration remains unknown. Here
      we show that in vitro treatment with IL-6 inhibited primary mouse hepatocyte
      proliferation. IL-6 induced p21cip1 protein expression in primary mouse
      hepatocytes. Disruption of the p21cip1 gene abolished the inhibitory effect of IL
      6 on cell proliferation. Co-culture with nonparenchymal liver cells diminished IL
      6 inhibition of hepatocyte proliferation, which was likely due to IL-6
      stimulation of nonparenchymal cells to produce HGF. Finally, IL-6 induced higher
      levels of p21cip1 protein expression and a slightly stronger inhibition of cell
      proliferation in SOCS3+/- mouse hepatocytes compared to wild-type hepatocytes,
      while liver regeneration was enhanced and prolonged in SOCS3+/- mice. Our
      findings suggest that IL-6 directly inhibits hepatocyte proliferation via a
      p21cip1-dependent mechanism and indirectly enhances hepatocyte proliferation via
      stimulating nonparenchymal cells to produce HGF. SOCS3 negatively regulates liver
      regeneration.

PMID- 16288984
TI  - A Stat5-overlapping site is critical for the IgJ enhancer activity in the plasma
      cells and bound by a ubiquitous protein.
AB  - Although the IgJ enhancer chromatin is induced open by an IL-2/Stat5 signaling
      during terminal B cell differentiation, the opened chromatin of IgJ enhancer is
      then maintained in the absence of IL-2/Stat5 signaling. Nevertheless, the
      sequence overlapping the Stat5 site was shown still to be essential for the
      function of IgJ enhancer in the plasma cells. An in vivo footprint was identified
      over the Stat5-overlapping site, indicating that the site should be bound by a
      certain other protein than Stat5. In EMSA using the Stat5-overlapping sequence as
      a probe, its specific binding protein was identified. The specific binding
      protein corresponded neither to any of other Stat family proteins, nor to any of
      potential candidate proteins as tested in EMSA using their corresponding oligo
      DNA competitors and antibodies. Although its identity remains to be found by its
      purification, the protein binding specifically to the Stat5-overlapping site was
      shown to be expressed rather ubiquitously in B and non-B cells, and its molecular
      weight appeared to be below 52 kDa as determined in the UV-crosslinking-coupled
      SDS-PAGE.

PMID- 16288985
TI  - CD24 is expressed specifically in the nucleus pulposus of intervertebral discs.
AB  - Intervertebral disc (IVD) consists of a soft gelatinous material in its center,
      the nucleus pulposus (NP), bounded peripherally by fibrocartilage, annulus
      fibrosus (AF). Despite the number of patients with IVD degeneration, gene
      expression analysis has not been undertaken in NP and therefore little is known
      about the molecular markers expressed in NP. Here, we undertook a microarray
      screen in NP with the other nine tissues to identify the specific cell surface
      markers for NP. Five membrane associating molecules out of 10,490 genes were
      identified as highly expressing genes in NP compared with the other tissues.
      Among them, we identified CD24, a glycosylphosphatidylinositol (GPI) anchor
      protein as a cell surface marker for NP. CD24 expression was also detected in the
      herniated NP and chordoma, a malignant primary tumor derived from notochordal
      cells, while it was absent in chondrosarcoma. Therefore, CD24 is a molecular
      marker for NP as well as the diseases of IVD.

PMID- 16288986
TI  - PPARalpha activation upregulates nephrin expression in human embryonic kidney
      epithelial cells and podocytes by a dual mechanism.
AB  - Nephrin is an important member of the glomerular ultrafiltration complex and
      changes in its expression are associated with severe proteinuria. In this study,
      we show that synthetic PPARalpha agonists, but not PPARgamma agonists, stimulate
      an increased nephrin mRNA and protein expression in cultures of human podocytes
      and A293 human embryonic kidney epithelial cells which are blocked by the
      PPARalpha antagonist Ru486. Furthermore, the PPARalpha agonists have an additive
      effect on the interleukin-1beta (IL-1beta)-induced nephrin upregulation.
      Luciferase-reporter assays reveal that human nephrin promoter activity is
      stimulated by the PPARalpha agonists. Neither IL-1beta nor TNFalpha alone has an
      effect on nephrin promoter activity suggesting that additional
      posttranscriptional regulatory events might be operative. The role of nephrin
      mRNA stability regulation was evaluated in cells treated with actinomycin D to
      stop further RNA transcription. In the presence of PPARalpha agonists, IL-1beta
      or TNFalpha, the decay of nephrin mRNA was drastically reduced thus arguing for
      an additional posttranscriptional mode of action. In summary, these data show
      that PPARalpha activation causes an increased nephrin expression by a dual
      action, on the one hand by stimulating nephrin promoter activity and on the other
      hand by reducing nephrin mRNA degradation. These findings may have importance for
      treatment strategies of renal diseases affecting the expression of nephrin and
      subsequently the proper action of the glomerular filtration apparatus.

PMID- 16288987
TI  - Molecular cloning and expression analysis of PDK family genes in Xenopus laevis
      reveal oocyte-specific PDK isoform.
AB  - Pyruvate dehydrogenase kinase (PDK) inactivates the multienzyme mitochondrial
      pyruvate dehydrogenase complex by the phosphorylation of three seryl residues in
      the pyruvate dehydrogenase moiety, and thus plays an important role in the
      control of glucose homeostasis. Genetically and biochemically distinct PDK family
      isozymes have been identified in mammalian species. In the present study, we
      demonstrate that the complete family of expressed PDK family genes in the tissues
      of the African clawed frog, Xenopus laevis, consists of four members, which are
      divided into two evolutionary groups. Xenopus PDKs (xPDKs) share an overall
      homology of about 70% to the human isoforms of PDK. The abundance of mRNAs for
      the four xPDK isoforms was analyzed by the real-time reverse transcriptase PCR
      technique in the various tissues of Xenopus laevis, including heart, lung,
      spleen, liver, kidney, skin, testis, oocytes, and eggs. Our data suggest that one
      of the xPDK isozymes can be referred to as an oocyte-specific xPDK. Functional
      differences between the xPDK isoforms are discussed, based on their different
      tissue-specific distributions and phylogenetic similarities to human PDKs.

PMID- 16288988
TI  - Glucose intolerance in young TallyHo mice is induced by leptin-mediated
      inhibition of insulin secretion.
AB  - The pathophysiology of TallyHo mouse, a recently established animal model for
      type 2 diabetes mellitus, was analyzed at prediabetic state to examine the
      inherent defects which contribute to the development of diabetes. At 4 weeks of
      age, the TallyHo mice already revealed glucose intolerance while their peripheral
      tissues exhibited normal insulin sensitivity. On the other hand, decreased plasma
      insulin concentration was observed with little differences in pancreatic insulin
      contents, indicating the impaired insulin secretion. Such defect, however, was
      not found in the isolated islets, which suggests a role of endocrine factor in
      impaired insulin secretion of TallyHo mice. Treatment of leptin inhibited the
      glucose-stimulated insulin secretion from the isolated islets of TallyHo mice,
      while in vivo administration of anti-leptin antibody lowered plasma glucose
      concentration with increased insulin level in TallyHo mice. Expression of
      glucokinase mRNA was decreased both in whole pancreas and leptin treated islets
      of TallyHo mice compared with whole pancreas in C57BL/6 mice and untreated islets
      of TallyHo mice, respectively. These results suggest that elevated plasma leptin
      can, through the inhibition of insulin secretion, induce glucose intolerance in
      TallyHo mice.

PMID- 16288989
TI  - Development of efficient expression system for protein display on bacterial
      magnetic particles.
AB  - Bacterial magnetic particles (BMPs) are utilized for various biomedical
      applications because they are easily manipulated by magnets, and functional
      proteins are easily displayed on BMPs. To establish highly expressed protein
      display on BMPs, strong promoters were identified using Magnetospirillum
      magneticum AMB-1 genome and proteome databases. Initially, several proteins
      highly expressed in AMB-1 were identified, and the upstream DNA sequences of the
      open-reading frames were evaluated using a luciferase-reporter gene assay to
      compare promoter activities. Consequently, luminescence intensity was 400 times
      higher due to the novel promoter identified in this study than the magA promoter
      previously used. Subsequently, efficient protein display on BMPs was performed
      using the newly identified promoter sequences. This developed display system will
      facilitate the assembly of various functional proteins onto BMPs to create novel
      magnetic nanoparticles.

PMID- 16288990
TI  - Drastic Ca2+ sensitization of myofilament associated with a small structural
      change in troponin I in inherited restrictive cardiomyopathy.
AB  - Six missense mutations in human cardiac troponin I (cTnI) were recently found to
      cause restrictive cardiomyopathy (RCM). We have bacterially expressed and
      purified these human cTnI mutants and examined their functional and structural
      consequences. Inserting the human cTnI into skinned cardiac muscle fibers showed
      that these mutations had much greater Ca2+-sensitizing effects on force
      generation than the cTnI mutations in hypertrophic cardiomyopathy (HCM). The
      mutation K178E in the second actin-tropomyosin (Tm) binding region showed a
      particularly potent Ca2+-sensitizing effect among the six RCM-causing mutations.
      Circular dichroism and nuclear magnetic resonance spectroscopy revealed that this
      mutation does not extensively affect the structure of the whole cTnI molecule,
      but induces an unexpectedly subtle change in the structure of a region around the
      mutated residue. The results indicate that the K178E mutation has a localized
      effect on a structure that is critical to the regulatory function of the second
      actin-Tm binding region of cTnI. The present study also suggests that both HCM
      and RCM involving cTnI mutations share a common feature of increased Ca2+
      sensitivity of cardiac myofilament, but more severe change in Ca2+ sensitivity is
      associated with the clinical phenotype of RCM.

PMID- 16288991
TI  - Aromatic l-aminoacid decarboxylase deficiency: unusual neonatal presentation and
      additional findings in organic acid analysis.
AB  - Aromatic l-aminoacid decarboxylase (AADC) deficiency is a neurotransmitter defect
      leading to a combined deficiency of catecholamines and serotonin. Patients are
      usually detected in infancy due to developmental delay, hypotonia, and
      extrapyramidal movements. Diagnosis is based on an abnormal neurotransmitter
      metabolite profile in CSF and reduced AADC activity in plasma. An elevation of
      vanillactic acid (VLA) has been described as the only abnormality detected in
      organic acid analysis (OA) of urine. We report a patient who presented in the
      neonatal period with lethargy, hypotonia, metabolic acidosis, and hypoglycemia.
      Blood ammonia, lactic acid, and acylcarnitines were normal, but OA of a urine
      sample showed a small increase of VLA, raising the suspicion of AADC deficiency.
      The patient was lost to follow-up until the age of 8 months, when he presented
      with dystonia, abnormal movements, oculogyric crises, and hypothermia. Repeat OA
      showed not only increased levels of VLA, but also increased vanilpyruvic acid
      (VPA), N-acetyl-vanilalanine (AVA) and N-acetyl-tyrosine (NAT). Neurotransmitter
      analysis in CSF showed increased vanilalanine (1200 nmol/L, ref<100) with
      decreased levels of 5-hydroxy-indoleacetic acid (5-HIAA, < 5 nmol/L; ref 152
      462), homovanillic acid (HVA, 83 nmol/L; ref 302-845), and methoxy-hydroxy-phenyl
      glycol (<5 nmol/L; ref 51-112). AADC activity in plasma was nearly undetectable.
      In the urine, low excretion of vanilmandelic acid (<0.3 micromol/mmol creat; ref
      0.3-20) and 5-HIAA (0.9 micromol/mmol creat; ref 4-18), was found, but HVA was
      normal and dopamine even elevated. This contradictory phenomenon of
      hyperdopaminuria has been described earlier in AADC deficient patients. We
      postulate that VPA and AVA could originate from vanilalanine (through a
      transaminase and an acetylase respectively), while NAT could originate from
      tyrosine through an AA acetylase. This report expands the clinical presentation
      of AADC deficiency and adds new markers of the disease for OA analysis, improving
      detection of AADC deficient patients in general metabolic screening procedures.

PMID- 16288993
TI  - Surveillance uncovers the smoking gun for resistance emergence.
AB  - Today, antibiotic resistance is becoming a major healthcare concern. As global
      travel increases, more antibiotic-resistant bacteria will be disseminated from
      one country to another, thereby imposing a problem worldwide. Since the
      development of resistance is an evolutionary process, constant surveillance is
      needed to gain insight into the problem and surveillance studies needed to
      document the spread of antibiotic resistance. The basic objectives of
      surveillance studies in antimicrobial resistance are: to determine the level of
      resistance in a particular geographical area; to monitor changes in the level of
      resistance and make this information available to therapeutic policy-makers, as
      well as to detect new mechanisms of resistance for use as early warning signs; to
      study how such resistance develops, persists and spreads, and to monitor
      interventions. Although, surveillance provides the smoking gun for emergence of
      antibiotic resistance, improvement of the system is necessary and may be achieved
      through enhanced information technology and diagnostic tools.

PMID- 16288992
TI  - Molecular cloning, functional characterization of the porcine transient receptor
      potential V1 (pTRPV1) and pharmacological comparison with endogenous pTRPV1.
AB  - In the present study, we cloned a porcine orthologue of transient receptor
      potential V1 (pTRPV1) and heterologously expressed it in human embryonic kidney
      (HEK) 293 cells to characterize its pharmacological properties. At the amino acid
      level, pTRPV1 was highly homologous (83-90%) to other orthologues of TRPV1. The
      expression of receptors was examined with current and [Ca2+]i responses to
      capsaicin using whole-cell patch-clamp and fura-2 ratio imaging techniques,
      respectively, and by immunostaining with an anti-TRPV1 antibody. The receptors
      were characterized by changes in [Ca2+]i in response to various vanilloid
      agonists, low pH and heat and by the effects of TRPV1 antagonists on them. The
      various TRPV1 agonists activated pTRPV1 in a dose-dependent manner in the order
      of potency of resiniferatoxin (RTX) > olvanil > capsaicin > phorbol 12
      phenylacetate 13-acetate 20-homovanillate (PPAHV), phorbol 12,13-dinonanoate 20
      homovanillate (PDNHV). Isovelleral and scutigeral had no effect. Endogenous
      vanilloids (anandamide > 15 (s)-HPETE >> NADA), low pH and noxious heat (>42
      degrees C) activated pTRPV1. Comparison of amino acid sequences with various
      mammalian TRPV1 homologues suggested some novel putative vanilloid recognition
      sites. TRPV1 antagonists, iodoRTX, ruthenium red and capsazepine suppressed
      capsaicin-induced responses. Similar to human TRPV1, but not rodent TRPV1,
      capsazepine was effective in blocking pH- and heat-induced responses. Similar
      pharmacological profiles were observed in cultured porcine dorsal root ganglion
      neurons. We discuss putative amino acid residues related to pharmacological
      differences among mammalian TRPV1 homologues.

PMID- 16288994
TI  - Estrogen receptor-independent inhibition of tumor necrosis factor-alpha gene
      expression by phytoestrogen equol is mediated by blocking nuclear factor-kappaB
      activation in mouse macrophages.
AB  - Equol has been suggested to possess protective effects on bone. However, the
      underlying mechanism of osteoprotective effect of equol has not been fully
      understood. In the present study, we examined the effect of equol on tumor
      necrosis factor-alpha (TNF-alpha) gene expression to elucidate a possible
      mechanism by which equol exerts osteoprotective effect. In vivo administration of
      equol inhibited TNF-alpha production by peritoneal macrophages isolated from LPS
      treated mice. Equol also dose-dependently inhibited TNF-alpha production and TNF
      alpha mRNA expression in LPS-stimulated mouse macrophages. Pretreatment of cells
      with ICI 182.780, an estrogen receptor antagonist, had no effect on the
      inhibitory efficacy of equol on LPS-induced TNF-alpha production. Further study
      demonstrated that equol inhibited NF-kappaB DNA binding and NF-kappaB-dependent
      reporter gene expression in activated RAW 264.7 cells. Moreover, equol blocked
      degradation of IkappaBalpha and IkappaBbeta and nuclear translocation of p65
      subunit of NF-kappaB in activated RAW 264.7 cells. These results suggest that the
      inhibitory effect of equol on TNF-alpha expression is mediated, at least in part,
      by blocking NF-kappaB activation and the inhibition of TNF-alpha expression by
      equol might be involved in its osteoprotective effect.

PMID- 16288995
TI  - Selective allosteric ligand activation of the retinoid X receptor heterodimers of
      NGFI-B and Nurr1.
AB  - NGFI-B, an orphan member of the NR4A subfamily of the nuclear receptors,
      recognizes specific sequences in the promoters of neuronal target genes as a
      monomer. Although NGFI-B also forms a heterodimer with the retinoid X receptor
      (RXR), a receptor for 9-cis retinoic acid (9CRA), endogenous targets of the
      heterodimer have not been identified. We investigated the role of RXR ligand
      binding in NGFI-B/RXR activation and found that dibenzodiazepine-derived ligands,
      such as the weak RXR agonist HX600, selectively activate NGFI-B/RXR heterodimers.
      HX600 also activated the heterodimer formed by RXR and Nurr1, another NR4A
      subfamily receptor. In an assembly assay that detects ligand-dependent
      reconstruction of the ligand-binding domain, HX600 and not 9CRA induced an
      allosteric ligand effect on NGFI-B through RXRalpha binding. The data indicate
      that the RXR heterodimers of NGFI-B and Nurr1 are selectively activated by the
      RXR ligand HX600, and that compounds such as HX600 will be valuable tools in
      investigating NGFI-B and Nurr1 function.

PMID- 16288996
TI  - Mechanisms involved in delta-aminolevulinic acid (ALA)-induced photosensitivity
      of tumor cells: relation of ferrochelatase and uptake of ALA to the accumulation
      of protoporphyrin.
AB  - Photodynamic therapy (PDT) using delta-aminolevulinic acid (ALA)-induced
      accumulation of protoporphyrin IX is a useful approach to the early detection and
      treatment of cancers. To investigate the role of ferrochelatase in the
      accumulation of protoporphyrin, we first made mouse fibroblast Balb/3T3 cells
      highly expressing ferrochelatase and examined the ALA-induced photo-damage as
      well as the accumulation of porphyrin in the cells. When the ferrochelatase
      transfected cells were treated with ALA and then exposed to visible light, they
      became resistant to the light without accumulating porphyrins, with a concomitant
      increase in the formation of heme. The accumulation of protoporphyrin was also
      abolished in human erythroleukemia K562 cells stably expressing mouse
      ferrochelatase. When mouse fibrosarcoma MethA cells, mouse fibroblast L929 cells
      and Balb/3T3 cells were treated with ALA, the greatest accumulation of
      protoporphyrin and the greatest level of cell death in response to the light were
      observed in MethA cells. The expression level of ferrochelatase was the lowest in
      MethA cells, while that of porphobilinogen deaminase was similar among all three
      cell lines. Moreover, an iron-chelator, desferrioxamine, which sequesters iron
      preventing the ferrochelatase reaction, enhanced the photo-damage as well as the
      accumulation of protoporphyrin in ALA-treated L929 cells. Thus, the light-induced
      cell death was tightly coupled with the accumulation of protoporphyrin caused by
      a decrease in ferrochelatase. Finally, we examined the uptake of ALA by MethA,
      L929 and Balb/3T3 cells. The extent of the uptake by MethA and L929 cells was
      greater, indicating a greater accumulation of protoporphyrin than in the Balb/3T3
      cells. Taken together, not only the low level of ferrochelatase but also the
      augmented uptake of ALA contributes to the ALA-induced accumulation of
      protoporphyrin IX and subsequent photo-damage in cancer cells.

PMID- 16288997
TI  - Synthesis and antinociceptive activity of cyclic endomorphin-2 and morphiceptin
      analogs.
AB  - Cyclic analogs of the opioid peptides endomorphin-2 and morphiceptin of the type
      Tyr-X-Phe-Phe-Y-NH2 and Tyr-X-Phe-D-Pro-Y-NH2 (X = Lys or Asp and Y = Lys or
      Asp), respectively, were synthesized in order to test their structure-activity
      relationships. Antinociceptive activity of the new analogs was assessed in the
      hot-plate test after intracerebroventricular administration in mice. The strong
      analgesic effect was observed for the analogs with Asp in position 2, while the
      analogs with Lys in the second position were inactive. Antinociception caused by
      Asp2 analogs was dose-dependent and reversed by the concomitant administration of
      the universal opioid antagonist naloxone and by the selective kappa antagonist,
      nor-BNI. However, receptor binding studies revealed poor affinity of all cyclic
      analogs at the mu-opioid receptor and no affinity at delta- and kappa-opioid
      receptors. It is most likely that the new cyclic analogs produced their
      antinociception by the release of dynorphin A, which subsequently acted on the
      kappa-opioid receptor.

PMID- 16288998
TI  - Cryptococcosis in human immunodeficiency virus-negative patients.
AB  - OBJECTIVE: To describe the clinical characteristics, treatment, and outcomes of
      cryptococcosis in HIV-negative patients. METHODS: HIV-negative adult patients
      with positive culture for Cryptococcus neoformans who attended Ramathibodi
      Hospital between 1987 and 2003 were retrospectively reviewed. RESULTS: During the
      17 year review period, 40 HIV-negative patients with cryptococcosis were
      identified. Of these, 37 patients had medical records available for study. The
      mean age was 49+/-18 (range 16-83) years and 73% were female. Twenty-four
      patients (65%) had associated underlying conditions. The most common associated
      conditions included immunosuppressive drug treatment (41%), presence of systemic
      lupus erythematosus (16%), malignancies (16%), and diabetes mellitus (14%). C.
      neoformans was mainly recovered from cerebrospinal fluid (32%), blood (28%), and
      sputum/bronchoalveolar lavage/lung tissue (28%). Twenty-three patients (62%) had
      disseminated cryptococcosis. Six of 14 patients with cryptococcal meningitis were
      asymptomatic. About half of the patients were treated with amphotericin B and
      subsequent fluconazole. Five patients (14%) were initially misdiagnosed and
      treated for tuberculosis or bacterial infection. The overall mortality rate was
      27%. CONCLUSIONS: Cryptococcosis is not rare in HIV-negative patients. The
      mortality rate is high. Early recognition of cryptococcosis and use of
      appropriate antifungal therapy in these patients may improve clinical outcomes.

PMID- 16288999
TI  - Conformational analysis of xylan chains.
AB  - The present study provides a theoretical description of the different levels of
      structural organization that characterize the xylan polysaccharide in its native
      and hydrophobic lauroyl esterified forms. The goal of this study was to ascertain
      the role played by the hydroxyl or lauroyl side groups on the conformational
      flexibility of the xylan chain backbone. The results reported provide a detailed
      description of the low-energy conformers of the dimer segments, a complete
      characterization of the helical structures, an insight into the disordered state
      of the polysaccharide chains and an estimation of the cohesion of the amorphous
      solids. Esterification of xylan hydroxyl groups by lauric acid has a large effect
      on the conformational properties of the glycosidic bonds linking two repeat
      units. Both the location and the relative energies of the low energy areas of the
      potential energy surfaces strongly differ: extended and coiled conformations are
      preferred for the native and hydrophobic forms, respectively. Consequently, the
      predicted unperturbed polymer chain extension strongly depends on the structure,
      predicted Lp of the native xylan of 35 A compares favourably well with the
      experimental ones, this characteristic dramatically decreases to 9A for the
      hydrophobically modified chain. Curiously, only extended 2(1) and left-handed
      3(1) helical structures are calculated stable for both polymers. The estimated
      cohesive parameters of amorphous bulks reveal that inter-chain interactions are
      stronger for the xylan chain than that for modified one, the former being
      stabilized by hydrogen bonds whereas hydrophobic interactions play a determinant
      role for the latter.

PMID- 16289000
TI  - Interactions between metal ions and carbohydrates. The coordination behavior of
      neutral erythritol to lanthanum and erbium ions.
AB  - Lanthanide ions and erythritol form metal-alditol complexes with various
      structures. Lanthanum nitrate and erbium chloride coordinate to erythritol to
      give new coordination structures. The lanthanum nitrate-erythritol complex
      (LaEN), 2La(NO3)3.C4H10O(4).8H2O, La3+ exhibits the coordination number of 11
      (namely 11 polar atoms bound to one lanthanum) and is 11-coordinated to two
      hydroxyl groups from one erythritol molecule, six oxygen atoms from three nitrate
      ions and three water molecules. One erythritol molecule is coordinated to two
      La3+ ions and links the two metal ions together. The ratio of M:L is 2:1. The
      erbium chloride-erythritol complex (ErE), ErCl2.C4H9O(4).2C2H5OH was obtained
      from ErCl3 and erythritol in aqueous ethanol solution and the structure shows
      that deprotonation reaction occurs in the reaction process. The Er3+ cation is 8
      coordinated with three hydroxyl groups of one erythritol molecule, two hydroxyl
      groups from another erythritol molecule, two ethanol molecules, and one chloride
      ion. Erythritol provides its three hydroxyl groups to one erbium cation and two
      hydroxyl groups to another erbium cation, that is, one hydroxyl group is
      coordinated to two metal ions and therefore loses its hydrogen atom and becomes a
      oxygen bridge. Another chloride ion is hydrogen bonded in the structure. The
      results indicate the complexity of metal-sugar coordination.

PMID- 16289001
TI  - Correlating Chlamydia trachomatis infectious load with urogenital ecological
      success and disease pathogenesis.
AB  - The association of infectious burden of Chlamydia trachomatis with patient
      characteristics and clinical disease may have implications for understanding
      disease pathogenesis. We examined chlamydial load from 171 urine samples where
      load was based on copy number of organisms per copy number of eukaryotic cells
      derived by real-time quantitative PCR. High- (E, F, G) and low-prevalence (Ia, H,
      J, Ja) genotypes in the population had similar loads, suggesting a similar
      propensity for replicating in vivo, despite their differential ecological
      success. Symptomatic and asymptomatic patients also had similar chlamydial loads,
      indicating that virulence differences are likely not associated with variations
      in replication. There was a significant difference in genotypes by age for F (<31
      years; P = 0.031) and for H where the mean age was lower than for the most
      prevalent genotype, E (P=0.013). Also, men had a significantly lower load than
      women when the genotype was F (P=0.042), although there was no significant
      difference in load between partners. Patients with recurrent chlamydial
      infections had a significant reduction in load with each subsequent episode
      regardless of genotype (P=0.007), suggesting that immune defenses do not block
      chlamydial entry but may impact replication. Additionally, the probability of
      being infected with J was 7.7-fold higher in patients with prior chlamydial
      infections (P=0.016), and although the loads were lower when compared with
      patients without prior infection, the results did not reach statistical
      significance. These findings suggest that chlamydial burden could be an important
      marker for recurrence and host immune response, which would facilitate
      pathogenesis research.

PMID- 16289002
TI  - Mycophenolate mofetil (MMF): firing at the atherosclerotic plaque from different
      angles?
AB  - Atherosclerosis is characterized by a persistent, low-grade inflammatory state in
      which immune cell activation is inseparably linked to plaque formation and
      destabilization. The T-lymphocyte in particular has emerged as a pivotal player
      throughout the course of atherogenesis. As a consequence, the concept that immune
      modulation is a suitable target for cardiovascular prevention is currently an
      important focus of research. Mycophenolate mofetil (MMF) has emerged as a non
      competitive inhibitor of inosine monophosphate dehydrogenase (IMPDH) that exerts
      cytostatic effects, particularly on proliferating T-lymphocytes. In addition, MMF
      has other immune-modulating effects, such as downregulation of the expression of
      adhesion molecules and attenuation of monocyte and macrophage responses. Given
      the added benefit that MMF is well tolerated, this immunosuppressive agent
      constitutes an attractive candidate for the modulation of inflammatory activation
      in atherogenesis. The present review provides an overview of the potential anti
      atherogenic properties of MMF.

PMID- 16289003
TI  - The role of natriuretic peptides in cardioprotection.
AB  - Atrial natriuretic peptide (ANP) and brain (B-type) natriuretic peptide (BNP) are
      circulating hormones of cardiac origin that play an important role in the
      regulation of intravascular blood volume and vascular tone. The plasma
      concentrations of ANP and BNP are elevated in heart failure, and they are
      considered to compensate for heart failure because of their diuretic,
      natriuretic, and vasodilating actions and inhibitory effects on renin and
      aldosterone secretion. Evidence is also accumulating from recent work that ANP
      and BNP exert their cardioprotective functions not only as circulating hormones
      but also as local autocrine and/or paracrine factors. In studies using cultured
      neonatal myocytes and fibroblasts, exogenous administration of both ANP and ANP
      antagonists demonstrated that ANP has antihypertrophic and antifibrotic
      functions. Corroborating these in vitro results, mice lacking natriuretic
      receptor-A (NPR-A), the receptor for ANP and BNP, develop cardiac hypertrophy and
      fibrosis independent of their blood pressure. Recent studies also suggest that
      the intracardiac natriuretic peptides/cGMP system plays a counter-regulatory role
      against the intracardiac renin-angiotensin-aldosterone system and TGF-beta
      mediated pathway. In a clinical setting, human recombinant ANP and BNP may be
      used for a therapy of heart failure; however, further evaluation is required in
      the future.

PMID- 16289004
TI  - Smad3 phosphorylation by cyclin-dependent kinases.
AB  - Smad3, a key mediator for TGF-beta antiproliferative responses, is phosphorylated
      by both CDK4 and CDK2 in vivo and in vitro. Except for the Rb family members,
      Smad3 is the only CDK4 substrate demonstrated so far. CDK phosphorylation of
      Smad3 inhibits its transcriptional activity and antiproliferative function.
      Because cancer cells often contain high levels of CDK activity, inhibition of
      Smad activity by CDK phosphorylation may contribute to tumorigenesis and TGF-beta
      resistance in cancers.

PMID- 16289005
TI  - Determinations of fluoroquinolones and nonsteroidal anti-inflammatory drugs in
      urine by extractive spectrophotometry and photoinduced spectrofluorimetry using
      multivariate calibration.
AB  - Multivariate calibration methods are chemometric tools that may be applied to the
      analysis of spectroscopic data with multichannel detection. Two procedures, based
      on spectrophotometric and fluorimetric signals, are reported for the simultaneous
      determination of two fluoroquinolones (ciprofloxacin and ofloxacin) and two
      nonsteroidal anti-inflammatory drugs (diclofenac and mefenamic acid) using first-
      and second-order multivariate calibration methods. In the spectrophotometric
      method, an extractive procedure into chloroform using trioctylmethylammonium
      chloride-adogen as counter ion was optimized, with the object of extracting the
      analytes from urine samples and eliminating matrix interferences. After
      separation, the absorption spectrum of the organic phase was used as the
      analytical signal in a partial least squares method. A photoinduced
      spectrofluorimetric (PIF) method using excitation-emission fluorescence matrices,
      is proposed, to apply three-way chemometric calibration, with the aim of
      analyzing ofloxacin, ciprofloxacin, and diclofenac in urine samples without the
      previous extractive sample-cleaning step. For both procedures, recoveries around
      100% were found for all the analytes. However, the PIF three-way chemometric
      method provides the most sensitive and selective procedure as the urine
      interferences are modulated using the three-way chemometric technique.

PMID- 16289006
TI  - High-throughput determination of malondialdehyde in plant tissues.
AB  - Malondialdehyde (MDA) is a widely used marker of oxidative lipid injury whose
      concentration varies in response to biotic and abiotic stress. Commonly, MDA is
      quantified as a strong light-absorbing and fluorescing adduct following reaction
      with thiobarbituric acid (TBA). However, plant tissues in particular contain many
      compounds that potentially interfere with this reaction and whose concentrations
      also vary according to the tissue type and stress conditions. As part of our
      studies into the stress responses of plant tissues, we were interested in
      developing a rapid, accurate, and robust protocol for MDA analysis using reverse
      phased HPLC to avoid these problems with reaction specificity. We demonstrate
      that a partitioning step into n-butanol during sample preparation is essential
      and that gradient HPLC analysis is necessary to prevent sample carryover between
      injections. Furthermore, the starting composition of the mobile phase must be
      sufficiently hydrophobic to allow direct injection of the n-butanol extracts
      without peak splitting, tailing, and other artifacts. To minimize analysis times,
      we used a short, so-called "Rocket" HPLC column and high flow rates. The
      optimized HPLC separation has a turnaround time of 2.5 min per sample. Butanolic
      extracts of MDA(TBA)(2) were stable for at least 48 h, and recoveries were linear
      between 0.38 and 7.5 pmol MDA added. Importantly, this procedure proved to be
      compatible with existing extraction procedures for l-ascorbate and glutathione
      analysis in different plant species, allowing multiple "stress metabolite"
      analyses to be carried out on a single tissue extract.

PMID- 16289007
TI  - Determining molecular binding sites on human serum albumin by displacement of
      oleic acid.
AB  - An NMR method was developed for determining binding sites of small molecules on
      human serum albumin (HSA) by competitive displacement of (13)C-labeled oleic
      acid. This method is based on the observation that in the crystal structure of
      HSA complexed with oleic acid, two principal drug-binding sites, Sudlow's sites I
      (warfarin) and II (ibuprofen), are also occupied by fatty acids. In two
      dimensional [(1)H,(13)C]heteronuclear single quantum coherence NMR spectra, seven
      distinct resonances were observed for the (13)C-methyl-labeled oleic acid as a
      result of its binding to HSA. Resonances corresponding to the major drug-binding
      sites were identified through competitive displacement of molecules that bind
      specifically to each site. Thus, binding of molecules to these sites can be
      followed by their displacement of oleic acids. Furthermore, the amount of bound
      ligand at each site can be determined from changes in resonance intensities. For
      molecules containing fluorine, binding results were further validated by direct
      observations of the bound ligands using (19)F NMR. Identifying the binding sites
      for drug molecules on HSA can aid in determining the structure-activity
      relationship of albumin binding and assist in the design of molecules with
      altered albumin binding.

PMID- 16289009
TI  - A direct fluorometric assay for tissue transglutaminase.
AB  - Herein we report the design of a direct and continuous fluorometric assay for
      determining tissue transglutaminase (TGase) activity. The progress of the TGase
      catalyzed reaction of 4-(N-carbobenzoxy-l-phenylalanylamino)-butyric acid
      coumarin-7-yl ester was monitored as an increase of fluorescence (lambda(exc) 330
      nm, lambda(em) 460 nm) due to the release of 7-hydroxycoumarin. Using this assay,
      we determined the K(m) of two acceptor substrates, N-acetyl-L-lysine methyl ester
      and aminoacetonitrile. We also determined the K(m) of 4-(N-carbobenzoxy-L
      phenylalanylamino)-butyric acid coumarin-7-yl ester for its TGase-mediated
      hydrolysis and for its enzymatic reaction with the acyl acceptor substrates N
      acetyl-L-lysine methyl ester and aminoacetonitrile. We ascertained that the
      fluorescent substrate was selective toward tissue TGase by testing it with
      different enzymes, namely microbial transglutaminase (mTGase), Factor XIIIa,
      papain, and gamma-glutamyl transpeptidase. 4-(N-carbobenzoxyglycinylamino)
      butyric acid coumarin-7-yl ester, lacking the benzyl side chain, was also found
      to be an efficient fluorogenic substrate of tissue TGase. Finally, we have shown
      that this method is applicable to 96-well microtiter plate format.

PMID- 16289008
TI  - Analysis of glucosinolates, isothiocyanates, and amine degradation products in
      vegetable extracts and blood plasma by LC-MS/MS.
AB  - Dietary glucosinolates are under intensive investigation as precursors of cancer
      preventive isothiocyanates. Quantitation of the dose and bioavailability of
      glucosinolates and isothiocyanates requires a comprehensive analysis of the major
      dietary glucosinolates, isothiocyanates, and related metabolites. We report a
      liquid chromatography with tandem mass spectrometric detection (LC-MS/MS)
      analytical method for the comprehensive analysis of the seven major dietary
      glucosinolates, related isothiocyanates, and putative amine degradation products.
      The parent glucosinolates were sinigrin, gluconapin, progoitrin, glucoiberin,
      glucoraphanin, glucoalyssin, and gluconasturtiin. The LC-MS/MS analysis method
      for these compounds was developed and validated; a standard addition analysis
      protocol was used generally to avoid the requirement for stable isotopic
      standards. Where stable isotopic standards were available, internal
      standardization with these gave estimates in agreement with those obtained by the
      standard addition analysis protocol. For glucosinolates, negative ion
      electrospray LC-MS/MS analysis was performed. Isothiocyanates and amines were
      prederivatized to the corresponding thiourea and N-acetamides, respectively, and
      were quantified by positive ion electrospray LC-MS/MS. The limits of detection
      were 0.5-2 pmol; the recoveries for glucosinolates, isothiocyanates, and amines
      were 85-90%, 50-85%, and 60-70%, respectively; and the intra- and interbatch
      coefficients of variation were 1-4% and 3-10%, respectively. These methods
      provide facile access to comprehensive analytical data on the major dietary
      glucosinolates and related metabolites to quantify inputs and metabolic formation
      of these compounds in cancer prevention and related studies.

PMID- 16289010
TI  - An assay for bacterial and eukaryotic chondroitinases using a chondroitin sulfate
      binding protein.
AB  - A simple, rapid, and reproducible microtiter-based chondroitinase (CSase) assay
      is reported here, based on the competition of chondroitin sulfate (CS) with
      immobilized hyaluronan (HA) for the binding of TSG-6 protein, the product of TNF
      inducible gene 6. Although the catabolic reaction of bacterial and other
      prokaryotic CSase enzymes, often referred to as the chondroitin lyases, can be
      followed by tracking the generation of unsaturated bonds by the
      spectrophotometrical determination of the absorbance at 232 nm, no rapid,
      sensitive, and simple assay has been devised to date for measuring the activity
      of the vertebrate enzymes that cleave their substrate exclusively by hydrolysis.
      We provide data demonstrating that the CSase assay described here is suitable for
      the determination of the activities of both classes of enzymes. For the bacterial
      enzyme CSase ABC, both the determination of the absorbance at 232 nm and the
      assay based on TSG-6 binding are suitable using the same range of enzyme
      activities. However, for testicular hyaluronidase, considerably higher enzyme
      activities were needed to cleave CS than to cleave HA. Using the HA-binding
      domain of aggrecan for a comparison, we determined that the interaction between
      TSG-6 and chondroitin sulfate is uniquely suited for this CSase assay.

PMID- 16289011
TI  - pH determination by pyranine: medium-related artifacts and their correction.
AB  - Pyranine (8-hydroxypyrene-1,3,6-trisulfonic acid) is a water-soluble, membrane
      impermeable fluorophore having fluorescent excitation and emission spectra that
      are highly dependent on medium pH. This combination makes it one of the most
      commonly used pH-sensitive fluorescent probes to monitor pH and pH changes in
      biochemical and biophysical research. The pK(a) of this probe is reported to be
      approximately 7.3, but several studies (including the current one) have shown
      that this value varies with medium composition. If this is not taken into
      account, pH determinations based on pyranine may be misleading. We found that in
      the presence of salts, pK(a) is shifted downward to lower values; therefore, the
      calculated pH is shifted upward relative to the actual pH as determined by a pH
      meter. This shift is a consequence of both the type and the concentration of
      anions and cations that form the salt. Divalent cations cause a larger upward
      shift in the calculated pH than do monovalent cations. Of all the salts tested,
      ammonium sulfate has the least effect, and calcium perchlorate has the largest
      effect, on the pH value calculated by pyranine. Salts are not the only species
      that affect the pK(a) of pyranine. The presence of the polymer polyethylene
      glycol (PEG) induces an effect opposite to that of salt (i.e., an upward pK(a)
      shift), which is expressed as pH being more acidic than that measured by a pH
      meter. Another nonelectrolyte, dextrose, has no such effect. The effect of both
      cations and anions can be explained based on their order in the Hofmeister
      series, whereas the effect of PEG is explained by its high water-binding
      capacity. Both the ions and PEG change the structure of water and its interaction
      with pyranine, thereby changing pyranine's apparent pK(a).

PMID- 16289012
TI  - Comparing the organophosphorus and carbamate insecticide resistance mutations in
      cholin- and carboxyl-esterases.
AB  - Mutant insect carboxyl/cholinesterases underlie over 60 cases of resistance to
      organophosphorus and/or carbamate insecticides. Biochemical and molecular data on
      about 20 of these show recurrent use of a very small number of mutational options
      to generate either target site or metabolic resistance. Moreover, the mutant
      enzymes are often kinetically inefficient and associated with significant fitness
      costs, due to impaired performance of the enzymes' original function. By contrast
      many bacterial enzymes are now known which can effectively detoxify these
      pesticides. It appears that the constraints of the genetic code and eukaryote
      genetic systems have severely limited the evolutionary response of insects to the
      widespread use of the insecticides over the last 60 years.

PMID- 16289013
TI  - Differential effects of selected natural compounds with anti-inflammatory
      activity on the glucocorticoid receptor and NF-kappaB in HeLa cells.
AB  - Natural compounds have been used in the treatment of various diseases for
      centuries. Herein, we investigated the effects of structurally diverse alkaloids
      with anti-inflammatory activity (berberine, sanguinarine, chelerythrine, and
      colchicine) on two important anti-inflammatory and pro-inflammatory players, i.e.
      glucocorticoid receptor (GR) and nuclear factor kappa B (NF-kappaB),
      respectively. Sanguinarine and chelerythrine elicited nuclear translocation of
      the p65 subunit of NF-kappaB. The nuclear import of p65 was strongly augmented by
      these akaloids in non-stimulated cells as well as in cells challenged with tumor
      necrosis factor alpha (TNFalpha). Colchicine and berberine had no effect on p65
      nuclear translocation regardless of the presence or absence of TNFalpha.
      Colchicine caused rapid degradation of the GR protein, whereas berberine had no
      effect on GR content or cellular localization. Sanguinarine and chelerythrine
      induced accumulation of GR in the nucleus with concomitant diminution of
      cytosolic GR. Analyses on the transcriptional activity of GR and NF-kappaB
      monitored by reporter assays using HeLa cells transiently transfected with
      glucocorticoid response element (pGRE-LUC) and/or NF-kappaB elements fused to
      luciferase gene (pNF-kappaB-luc) showed that none of the compounds tested had the
      capability to trigger GR and/or NF-kappaB transcriptional activities,
      respectively. The ligand binding assay showed that colchicine and berberine are
      not GR ligands whereas sanguinarine and chelerythrine significantly decreased
      binding of (3)H-labelled dexamethasone to GR. In conclusion, structurally diverse
      natural antiflogistics displayed differential effects on GR and NF-kappaB in HeLa
      cells.

PMID- 16289014
TI  - The role of AChE active site gorge in determining stereoselectivity of charged
      and noncharged VX enantiomers.
AB  - The reactivity of human acetylcholinesterase (HuAChE) toward the chemical warfare
      agent VX [O-ethyl S-[2-(diisopropylamino)ethyl] methyl-phosphonothioate] and its
      stereoselectivity toward the P(S)-enantiomer were investigated by examining the
      reactivity of HuAChE and its mutant derivatives toward purified enantiomers of VX
      and its noncharged isostere nc-VX [O-ethyl S-(3-isopropyl-4-methyl-pentyl)
      methylphosphonothioate]. Stereoselectivity of the wild-type HuAChE toward VX(S)
      is manifested by a 115-fold higher bimolecular rate constant (1.4 x 10(8) min(-1)
      M(-1)) as compared to that of VX(R). HuAChE was also 12,500-fold more reactive
      toward VX(S) than toward nc-VX(S), demonstrating the significance of the polar
      interactions of the ammonium substituent to their overall affinity toward VX.
      Indeed, substitution of the cation-binding subsite residue Trp86 by alanine
      resulted in a decrease of three orders of magnitude in HuAChE reactivity toward
      both VX enantiomers, with only a marginal effect on the reactivity toward the
      enantiomers of nc-VX. These results demonstrate that accommodation of the charged
      moieties of both VX enantiomers depends predominantly on interactions with the
      aromatic moiety of Trp86. Yet, these interactions seem to limit the
      stereoselectivity toward the P(S)-enantiomer, which for charged
      methylphosphonates is much lower than for the noncharged analogs, like sarin or
      soman. Marked decrease in stereoselectivity toward VX(S) was observed following
      replacements of Phe295 at the acyl pocket (F295A and F295A/F297A). Replacement of
      the peripheral anionic site (PAS) residue Asp74 by asparagine (D74N) practically
      abolished stereoselectivity toward VX(S) (a 130-fold decrease), while
      substitution which retained the negative charge at position 74 (D74E) had no
      effect. The results from kinetic studies and molecular simulations suggest that
      the differential reactivity toward the VX enantiomers originates predominantly
      from a different orientation of the charged leaving group with respect to residue
      Asp74. Such different orientations of the charged leaving group in the HuAChE
      adducts of the VX enantiomers seem to be a consequence of intramolecular
      interactions with the bulky phosphorus alkoxy group.

PMID- 16289015
TI  - The role of a novel copper complex in overcoming doxorubicin resistance in
      Ehrlich ascites carcinoma cells in vivo.
AB  - One of the important pathways of resistance to anthracyclines is governed by
      elevated levels of glutathione (GSH) in cancer cells. Resistant cells having
      elevated levels of GSH show higher expression of multidrug-resistant protein
      (MRP); the activity of glutathione S-transferases (GSTs) group of enzymes have
      also been found to be higher in some drug-resistant cells. The general mechanism
      in this type of resistance seems to be the formation of conjugates enzymatically
      by GSTs, and subsequent efflux by active transport through MRP (MRP1-MRP9). MRPs
      act as drug efflux pump and can also co-transport drugs like doxorubicin (Dox)
      with GSH. Depletion of GSH in resistant neoplastic cells may possibly sensitize
      such cells, and thus overcome multidrug resistance (MDR). A number of resistance
      modifying agents (RMA) like DL-buthionine (S, R) sulfoxamine (BSO) and ethacrynic
      acid (EA) moderately modulate resistance by acting as a GSH-depleting agent. As
      most of the GSH-depleting agents have dose-related toxicity, development of non
      toxic GSH-depleting agent has immense importance in overcoming MDR. The present
      study describes the resistance reversal potentiality of novel copper complex,
      viz., copper N-(2-hydroxy acetophenone) glycinate (CuNG) developed by us in Dox
      resistant Ehrlich ascites carcinoma (EAC/Dox) cells. CuNG depletes GSH in
      resistant (EAC/Dox) cells possibly by forming conjugate with it. Depletion of GSH
      results in higher Dox accumulation that may lead to enhanced rate of apoptosis in
      EAC/Dox cells. In vivo studies with male Swiss albino mice bearing ascitic growth
      of EAC/Dox showed tremendous increase in life span (treated/control, T/C = 453%)
      for the treated group with apparent regression of tumor. Resistance to Dox in
      EAC/Dox cells is associated with over expression of GST-P1, GST-M1 (enzymes
      involved in phase II detoxification) and MRP1 (a transmembrane ATPase efflux pump
      for monoglutathionyl conjugates of xenobiotics). CuNG causes down regulation of
      all these three proteins in EAC/Dox cells. The effect of CuNG as RMA is better
      than BSO in many aspects.

PMID- 16289016
TI  - Free and bound enantiomers of methadone and its metabolite, EDDP in methadone
      maintenance treatment: relationship to dosage?
AB  - OBJECTIVES: To determine the effects of metabolism and protein binding on the
      relationship between administered dose, blood levels of R methadone and
      biological response by measuring the free and protein-bound forms of the R and S
      enantiomers of methadone and EDDP, its metabolite. DESIGN AND METHODS: To measure
      free and total drug, trough levels were collected from 45 methadone clients. To
      measure free methadone, samples were filtered using ultrafiltration with a MW
      weight cut-off of 10,000 and extracted using liquid-liquid extraction. The
      solvent was evaporated and samples reconstituted in mobile phase for analysis by
      LC/MS/MS. Total analyte was determined by extracting unfiltered samples.
      Enantiomeric separation of methadone and EDDP was by chiral chromatography.
      RESULTS: The presence of unmetabolized methadone suggested that none of the
      patients were very fast metabolizers. R and S forms were metabolized at the same
      rate at all administered doses. Free R methadone levels correlated both with
      methadone dose and with the total amount of R methadone. The free fraction of R
      methadone (%free R) was higher at lower doses than at high doses, varied from 5
      to 25% and was inversely proportional to the total dose of administered drug in a
      relationship that was logarithmic and non-linear. CONCLUSIONS: By measuring the
      free, biologically active form of the drug, we were unable to account for the
      large variations in dose required between different patients to prevent the onset
      of withdrawal symptoms. The reason for the large range in dosage may be
      multifactorial.

PMID- 16289017
TI  - Postural versus chair design impacts upon interface pressure.
AB  - An investigation of postural and chair design impacts upon seat pan interface
      pressure has been performed in an effort to identify whether differences in
      posture or chair design result in greater pressure differences. Investigation of
      postural variables focused on trunk-thigh angle and use of armrests. Twelve
      ergonomic office chairs were used to assess chair design differences. Both male
      and female subjects were included. Gender effects were controlled through use of
      a repeated Latin square design, with squares defined by gender. Significant
      gender-based interaction was observed amongst postural treatments and chair
      effects. Postural treatments, chairs designs, and participant effects all
      resulted in significant interface pressure differences, though gender-based
      interaction yielded some non-additivity of results between males and females. The
      final conclusion drawn from the results is that chair design differences had the
      greatest effect on seat pan interface pressure, followed by participant effects,
      and lastly postural treatments.

PMID- 16289018
TI  - Wavelet-based estimation of EEG coherence during Chinese Stroop task.
AB  - Wavelet-based estimation of instantaneous EEG coherence was applied to
      investigate the synchronization of different brain regions whilst 10 subjects
      performing Stroop task presented in Chinese. In contrast to coherence based on
      Fourier transform, wavelet-based coherence, which does not depend on the
      stationarity of signals, applies an adaptive window to the frequency of the
      signal and has a more accurate time-frequency resolution. In the present study, a
      greater negativity for the incongruent situation than congruent situation
      appeared from 350 to 600 ms post-stimulus onset over frontal, central, and
      parietal regions, and significantly higher EEG coherences for the incongruent
      situation than congruent situation were observed over frontal, parietal, and
      frontoparietal regions from 100 to 400 ms at beta1 (13-18Hz) frequency band,
      which was found to be sensitive in the discrimination between congruent and
      incongruent situations. The findings in the present study may indicate that
      functional synchronization as indexed by EEG coherence at beta1 frequency band is
      enhanced at the earlier stage while processing the conflicting information from
      the incongruent stimulus, and that beta1 frequency band is close related to
      interactions of brain areas in the selected attention task.

PMID- 16289019
TI  - Interactions within the ClpB/DnaK bi-chaperone system from Escherichia coli.
AB  - ClpB and DnaK form a bi-chaperone system that reactivates strongly aggregated
      proteins in vivo and in vitro. Previously observed interaction between purified
      ClpB and DnaK suggested that one of the chaperones might recruit its partner
      during substrate reactivation. We show that ClpB from Escherichia coli binds at
      the substrate binding site of DnaK and the interaction is supported by the N
      terminal domain and the middle domain of ClpB. Moreover, the interaction between
      ClpB and DnaK depends on the nucleotide-state of DnaK: it is stimulated by ADP
      and inhibited by ATP. These observations indicate that DnaK recognizes selected
      structural motifs in ClpB as "pseudo-substrates" and that ClpB may compete with
      bona fide substrates of DnaK. We conclude that direct interaction between ClpB
      and DnaK does not mediate a substrate transfer between the chaperones, it may,
      however, play a role in the recruitment of the bi-chaperone system to specific
      recognition sites in aggregated particles.

PMID- 16289020
TI  - Trehalose and glycerol stabilize and renature yeast inorganic pyrophosphatase
      inactivated by very high temperatures.
AB  - A number of naturally occurring small organic molecules, primarily involved in
      maintaining osmotic pressure in the cell, display chaperone-like activity,
      stabilizing the native conformation of proteins, and protecting them from various
      kinds of stress. Most of them are sugars, polyols, amino acids or methylamines.
      Similar to molecular chaperones, most of these compounds have no substrate
      specificity, but some specifically stabilize certain proteins. In the present
      work, the capacity of trehalose and glycerol, two well-known osmolytes, to
      stabilize and renature inorganic pyrophosphatase is demonstrated. Both trehalose
      and glycerol significantly protect pyrophosphatase against thermoinactivation
      achieved by incubating the enzyme at temperatures up to 95 degrees C, and allow
      the enzyme already inactivated in the presence of these osmolytes to renature
      upon incubation at low temperatures. To the best of our knowledge, there are no
      data on the effects of these compounds on renaturation of thermoinactivated
      proteins. The correlation between the recovery of enzyme activity and structural
      changes indicated by fluorescence spectroscopy contribute to better understanding
      of the protein stabilization mechanism.

PMID- 16289021
TI  - Activation of chondrocytes calcium signalling by dynamic compression is
      independent of number of cycles.
AB  - Mechanical loading is necessary for the development and maintenance of healthy
      articular cartilage through the control of extracellular matrix synthesis and
      catabolism. However, the underlying process of chondrocyte mechanotransduction
      remains unclear. This study examined the influence of cyclic compression on
      intracellular calcium (Ca(2+)) signalling within isolated articular chondrocytes
      cultured in agarose constructs. A validated experimental system was developed for
      applying controlled cyclic cell deformation. Cell-agarose constructs were
      subjected to 1Hz cyclic compression between 0 and 10% gross strain for 1, 10, 100
      or 300 cycles. The cells were subsequently visualised for 300s in the unstrained
      state using confocal microscopy and the Ca(2+) indicator, Fluo-4 AM. Within
      unloaded control constructs, a sub-population of approximately 50% of
      chondrocytes exhibited characteristic spontaneous Ca(2+) transients each lasting
      approximately 40-60s. Cyclic compression, for only 1 cycle, significantly up
      regulated the percentage of cells exhibiting Ca(2+) transients in the subsequent
      5min period (p<0.05). Increasing the number of cycles to 10 or 100 had no
      additional effect. The up-regulated Ca(2+) signalling was maintained for up to
      5min before returning to basal levels. By contrast, 300 cycles were followed by
      Ca(2+) signalling that was not significantly different from that in unloaded
      controls. However, this response was shown to be due to the increased time
      following the start of compression. In conclusion, this study indicates that
      chondrocyte Ca(2+) signalling is stimulated by dynamic compression, probably
      mediated by cyclic cell deformation. The overall response appears to be
      independent of the number of cycles or duration of cyclic compression. The
      sustained up-regulation of Ca(2+) signalling after 1, 10 or 100 cycles suggests
      the involvement of an autocrine-paracrine signalling mechanism. Furthermore, the
      reduced response following 300 cycles indicates a possible receptor
      desensitisation mechanism. Therefore, Ca(2+) signalling may be part of a
      mechanotransduction pathway through which chondrocyte populations can modulate
      their metabolic activity in response to changing mechanical stimuli.

PMID- 16289023
TI  - The ligand geometry of copper determines the stability of amicyanin.
AB  - Solution differential scanning calorimetry (DSC) of oxidized amicyanin, a Type I
      copper protein, at pH 7.5 reveals two thermal transitions. The major transition
      at 67.7 degrees C corresponds to the disruption of the Cys(92) thiolate to Cu(II)
      charge transfer as evidenced by a corresponding temperature-dependent loss of
      amicyanin visible absorbance. A minor transition at 75.5 degrees C describes the
      further irreversible protein unfolding. Reduced amicyanin exhibits a pH-dependent
      change of the copper ligand geometry. At pH 8.5 where the Type I tetrahedral
      geometry is maintained, DSC reveals two thermal transitions with T(m) values
      similar to that of oxidized amicyanin. At pH 6.2 where the Cu(I) coordination is
      trigonal planar, reduced amicyanin exhibits a single thermal transition with a
      lower T(m) of 64.0 degrees C. Apoamicyanin, from which copper has been removed,
      also exhibits a single thermal transition but with a much lower T(m) of 51.8
      degrees C. Thus, the thermal stability of amicyanin is dictated both by the
      presence or absence of copper and its ligand geometry, but not its redox state.
      The physiological relevance of these data is discussed.

PMID- 16289022
TI  - ADAMTS-4 (aggrecanase-1): N-terminal activation mechanisms.
AB  - ADAMTS-4 (aggrecanase 1) is synthesized as a latent precursor protein that may
      require activation through removal of its prodomain before it can exert catalytic
      activity. We examined various proteinases as well as auto-activation under a wide
      range of conditions for removal of the prodomain and induction of enzymatic
      activity. The proprotein convertases, furin, PACE4, and PC5/6 efficiently removed
      the prodomain through cleavage at Arg(212)/Phe(213), generating an active enzyme.
      Of a broad range of proteases evaluated, only MMP-9 and trypsin were capable of
      removing the prodomain. In the presence of mercuric compounds, removal of the
      prodomain through autocatalysis was not observed, nor was it observed at
      temperatures from 22 to 65 degrees C, at ionic strengths from 0.1 to 1M, or at
      acidic/neutral pH. At basic pH 8-10, removal of the prodomain by autocatalysis
      occurred, generating an active enzyme. In conclusion, the pro-form of ADAMTS-4 is
      not catalytically active and only a limited number of mechanisms mediate its N
      terminal activation.

PMID- 16289024
TI  - cis-Regulatory inputs of the wnt8 gene in the sea urchin endomesoderm network.
AB  - Expression of the wnt8 gene is the key transcriptional motivator of an
      intercellular signaling loop which drives endomesoderm specification forward
      early in sea urchin embryogenesis. This gene was predicted by network
      perturbation analysis to be activated by inputs from the blimp1/krox gene, itself
      expressed zygotically in the endomesoderm during cleavage; and by a Tcf1/beta
      catenin input. The implication is that zygotic expression of wnt8 is stimulated
      in neighboring cells by its own gene product, since reception of the Wnt8 ligand
      causes beta-catenin nuclearization. Here, the modular cis-regulatory system of
      the wnt8 gene of Strongylocentrotus purpuratus was characterized functionally,
      and shown to respond to blockade of both Blimp1/Krox and Tcf1/beta-catenin inputs
      just as does the endogenous gene. The genomic target sites for these factors were
      demonstrated by mutation in one of the cis-regulatory modules. The Tcf1/beta
      catenin and Blimp1/Krox inputs are both necessary for normal endomesodermal
      expression mediated by this cis-regulatory module; thus, the genomic regulatory
      code underlying the predicted signaling loop thus resides in the wnt8 cis
      regulatory sequence. In a second regulatory region, which initiates expression in
      micromere and macromere descendant cells early in cleavage, Tcf1 sites act to
      repress ectopic transcription in prospective ectoderm cells.

PMID- 16289026
TI  - Primitive streak formation in mice is preceded by localized activation of
      Brachyury and Wnt3.
AB  - The prevalent model for the generation of axial polarity in mouse embryos
      proposes that a radial to a linear transition in the expression of primitive
      streak markers precedes the formation of the primitive streak on one side of the
      epiblast. This model contrasts with the models of mesoderm formation in other
      vertebrates as it suggests that the primitive streak is initially established in
      a radial pattern rather than a localized region of the epiblast. Here, we examine
      the proposed correlation between the expression of Brachyury and Wnt3, two genes
      reported as expressed radially in the proximal epiblast, with the movements of
      proximal anterior epiblast cells at stages leading to the formation of the
      primitive streak. Our results reveal that neither Brachyury nor Wnt3 forms a ring
      of expression in the proximal epiblast as previously thought. In embryos
      dissected between 5.5 and 6.5 dpc, Brachyury is first expressed in the distal
      extra-embryonic ectoderm and subsequently on one side of the epiblast. Wnt3
      expression is evident first in the posterior visceral endoderm of 5.5 dpc embryos
      and later in the posterior epiblast. Lineage analysis shows that the movements of
      the proximal epiblast do not restrict Brachyury expression to the posterior
      epiblast. Our data suggest a model whereby the localized expression of these
      genes in the posterior epiblast, and hence the formation of the primitive streak,
      is the result of local cell-cell interactions in the future posterior portion of
      the egg cylinder rather than regionalization of a radial pattern of expression in
      proximal epiblast cells.

PMID- 16289025
TI  - Organisation of the lamprey (Lampetra fluviatilis) embryonic brain: insights from
      LIM-homeodomain, Pax and hedgehog genes.
AB  - To investigate the embryonic development of the central nervous system of the
      lamprey Lampetra fluviatilis, we have isolated and analysed the expression
      patterns of members of the LIM-homeodomain, Pax, Hedgehog and Nkx2.1 families.
      Using degenerate RT-PCR, single representatives of Lhx1/Lhx5, Lhx2/Lhx9,
      Pax3/Pax7 and Hedgehog families could be isolated in L. fluviatilis. Expression
      analysis revealed that the lamprey forebrain presents a clear neuromeric pattern.
      We describe the existence of 4 embryonic diencephalic prosomeres whose boundaries
      can be identified by the combined and relative expressions of LfPax37, LfLhx15
      and LfLhx29. This suggests that the embryonic lamprey and gnathostome forebrain
      are patterned in a highly similar manner. Moreover, analysis of the LfHh gene,
      which is expressed in the hypothalamus, zona limitans intrathalamica and floor
      plate, reveals the possible molecular origin of this neuromeric brain pattern. By
      contrast, LfHh and LfNkx2.1 expressions suggest major differences in patterning
      mechanisms of the ventral telencephalon when compared to gnathostomes. In
      summary, our findings highlight a neuromeric organisation of the embryonic
      agnathan forebrain and point to the possible origin of this organisation, which
      is thus a truly vertebrate character. They also suggest that Hh/Shh midline
      signalling might act as a driving force for forebrain evolution.

PMID- 16289027
TI  - The interaction of 5'-adenylylsulfate reductase from Pseudomonas aeruginosa with
      its substrates.
AB  - APS reductase from Pseudomonas aeruginosa has been shown to form a disulfide
      linked adduct with mono-cysteine variants of Escherichia coli thioredoxin and
      Chlamydomonas reinhardtii thioredoxin h1. These adducts presumably represent
      trapped versions of the intermediates formed during the catalytic cycle of this
      thioredoxin-dependent enzyme. The oxidation-reduction midpoint potential of the
      disulfide bond in the P. aeruginosa APS reductase/C. reinhardtii thioredoxin h1
      adduct is -280 mV. Site-directed mutagenesis and mass spectrometry have
      identified Cys256 as the P. aeruginosa APS reductase residue that forms a
      disulfide bond with Cys36 of C. reinhardtii TRX h1 and Cys32 of E. coli
      thioredoxin in these adducts. Spectral perturbation measurements indicate that P.
      aeruginosa APS reductase can also form a non-covalent complex with E. coli
      thioredoxin and with C. reinhardtii thioredoxin h1. Perturbation of the resonance
      Raman and visible-region absorbance spectra of the APS reductase [4Fe-4S] center
      by either APS or the competitive inhibitor 5'-AMP indicates that both the
      substrate and product bind in close proximity to the cluster. These results have
      been interpreted in terms of a scheme in which one of the redox-active cysteine
      residues serves as the initial reductant for APS bound at or in close proximity
      to the [4Fe-4S] cluster.

PMID- 16289028
TI  - Attenuation of morphine withdrawal signs by intracerebral administration of 18
      methoxycoronaridine.
AB  - 18-Methoxyroconaridine (18-MC), a synthetic derivative of ibogaine, reduces
      morphine self-administration and alleviates several signs of acute opioid
      withdrawal in rats. Although there is already well documented evidence of the
      mechanism mediating 18-MC's action to reduce the rewarding effects of morphine,
      nothing is known about the mechanism responsible for 18-MC's attenuation of
      opioid withdrawal. In vitro studies have demonstrated that 18-MC is a potent
      antagonist of alpha3beta4 nicotinic receptors (IC50=0.75 microM), which are
      predominantly located in the medial habenula and interpeduncular nuclei. Previous
      work indicating that alpha3beta4 nicotinic receptors mediate 18-MC's effects on
      drug self-administration prompted us to assess whether brain areas having high or
      moderate densities of alpha3beta4 receptors might be involved in 18-MC's
      modulation of opioid withdrawal. To test this possibility, 18-MC was locally
      administered into the medial habenula, interpeduncular nucleus and locus
      coeruleus of morphine-dependent rats; this treatment was followed by naltrexone
      to precipitate a withdrawal syndrome. Pretreatment with various doses of 18-MC
      into the locus coeruleus significantly reduced wet-dog shakes, teeth chattering,
      burying and diarrhea, while pretreatment into the medial habenula attenuated
      teeth chattering, burying, and weight loss. Some doses of 18-MC administered into
      the interpeduncular nucleus significantly ameliorated rearing, teeth chattering,
      and burying, while other doses exacerbated diarrhea and teeth chattering. The
      present findings suggest that 18-MC may act in all three nuclei to suppress
      various signs of opioid withdrawal.

PMID- 16289029
TI  - Serotonin and aggressive behavior in rodents and nonhuman primates:
      predispositions and plasticity.
AB  - This review analyzes psychosocial and genetic determinants of aggressive behavior
      in rodents and nonhuman primates and the role of the serotonin (5-HT) system on
      aggressive behaviors in order to trace possible evolutionary common origins
      between psychopathological and adaptive forms of aggression. Studies in primates
      suggest that deficit in serotonin activity, as indicated by the levels of the
      cerebrospinal fluid (CSF) serotonin major metabolite 5-hydroxyindoleacetic acid
      (5-HIAA) correlates with impulsive and aggressive behavior. It is possible that
      CSF 5-HIAA reflects the prevailing serotonergic tone and may be related to an
      aggressive trait. Superimposed on this tone are phasic serotonin changes that may
      be related to the inhibition of aggressive acts. Genetic factors determine
      aggressive behaviors as demonstrated by classic selection and strain comparison
      studies. Manipulations of genes targeting 5-HT receptors, transporters and
      enzymes can influence aggression. Some of these genes related to the serotonin
      transporter (5-HTT) and the monoamine oxidase A (MAO-A) show a polymorphism that
      may predispose, under specific environmental conditions, certain individuals to
      display pathological forms of aggression.

PMID- 16289030
TI  - [3H]N-[4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)butyl]-2-methoxy-5
      methylbenzamide: a novel sigma-2 receptor probe.
AB  - N-[4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)butyl]-2-methoxy-5-methyl
      benzamide (RHM-1) and N-[2-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)ethyl]
      2-methoxy-5-methylbenzamide (RHM-2), two conformationally flexible benzamide
      analogues, were radiolabeled with tritium (specific activity=80 Ci/mmol) and the
      binding of [3H]RHM-1 and [3H]RHM-2 to sigma-2 (sigma2) receptors was evaluated in
      vitro. [3H]RHM-1 was found to have a higher affinity for sigma2 receptors
      compared to [3H]RHM-2 and [3H]1,3-di-o-tolylguanidine ([3H]DTG). [3H]RHM-1 had a
      dissociation constant (Kd) of 0.66+/-0.12 nM in rat liver membrane homogenates,
      which was 30-fold higher than that of [3H]RHM-2 (Kd=19.48+/-0.51 nM). The lower
      affinity of [3H]RHM-2 can be attributed to its faster K(off) rate since both
      radioligands have similar K(on) rates. Competitive binding assays were also
      conducted using a panel of compounds with known affinity for sigma2 receptors.
      The pharmacologic profile of [3H]RHM-1 was in agreement with that of [3H]DTG. The
      results of this study indicate that [3H]RHM-1 is a useful ligand for studying
      sigma2 receptors in vitro.

PMID- 16289031
TI  - 1'-Acetoxychavicol acetate induces apoptosis of myeloma cells via induction of
      TRAIL.
AB  - A component of a traditional Thai condiment, 1'-acetoxychavicol acetate (ACA), is
      a natural compound, and it is obtained from rhizomes of the ethno-medicinal plant
      Languas galanga (Zingiberaceae). Our previous studies showed that ACA
      dramatically inhibited cellular growth of multiple myeloma cells in vivo and in
      vitro through the induction of apoptosis in association with the activation of
      caspase-8, inactivation of NF-kappaB, and down-regulation of anti-apoptotic
      proteins. Subsequently, we investigated the detailed apoptotic pathway of ACA and
      further demonstrated that ACA up-regulates the expression of both TNF-related
      apoptosis-inducing ligand/Apo2 ligand (TRAIL/Apo2L) and TRAIL receptor death
      receptor 5 (DR5). In addition, TRAIL/R-Fc chimera neutralizes the ACA-induced
      apoptosis. These results suggest that the death signaling of TRAIL is involved in
      the ACA-induced apoptosis of myeloma cells, and provide a rationale for the
      induction of TRAIL/Apo2L by ACA, which could potentially be used as a novel
      therapeutic agent in patients with multiple myeloma.

PMID- 16289032
TI  - Identification of human and rat FAD-AMP lyase (cyclic FMN forming) as ATP
      dependent dihydroxyacetone kinases.
AB  - Rat liver FAD-AMP lyase or FMN cyclase is the only known enzymatic source of the
      unusual flavin nucleotide riboflavin 4',5'-cyclic phosphate. To determine its
      molecular identity, a peptide-mass fingerprint of the purified rat enzyme was
      obtained. It pointed to highly related, mammalian hypothetical proteins
      putatively classified as dihydroxyacetone (Dha) kinases due to weaker homologies
      to biochemically proven Dha kinases of plants, yeasts, and bacteria. The human
      protein LOC26007 cDNA was used to design PCR primers. The product amplified from
      human brain cDNA was cloned, sequenced (GenBank Accession No. ), and found to
      differ from protein LOC26007 cDNA by three SNPs. Its heterologous expression
      yielded a protein active both as FMN cyclase and ATP-dependent Dha kinase, each
      activity being inhibited by the substrate(s) of the other. Cyclase and kinase
      activities copurified from rat liver extracts. Evidence supports that a single
      protein sustains both activities, probably in a single active center. Putative
      Dha kinases from other mammals are likely to be FMN cyclases too. Future work
      will profit from the availability of the structure of Citrobacter freundii Dha
      kinase, which contains substrate-interacting residues conserved in human Dha
      kinase/FMN cyclase.

PMID- 16289033
TI  - MKP-1 contributes to oxidative stress-induced apoptosis via inactivation of
      ERK1/2 in SH-SY5Y cells.
AB  - Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) is a dual
      specificity phosphatase that negatively regulates the MAP kinases. In this study,
      we found that levels of MKP-1 expression were transiently decreased within 3h,
      followed by an increase 6-9h after H2O2-induced oxidative stress in human
      neuroblastoma SH-SY5Y cells. There was a strong negative correlation between MKP
      1 expression and ERK1/2 phosphorylation levels. Treatment of cells with a
      proteasomal inhibitor MG132 decreased the oxidative stress-induced degradation of
      MKP-1, resulting in dephosphorylation of ERK1/2. MG132 potentiated hydrogen
      peroxide-induced cell death, which was attenuated by a phosphatase inhibitor
      sodium orthovanadate. Suppression of MKP-1 expression by transfection with siRNA
      duplexes specific to MKP-1 transcript resulted in a decrease in oxidative stress
      induced cell death. These data therefore suggest that MKP-1, a negative regulator
      of ERK1/2, plays a proapoptotic role in oxidative stress-induced cell death in a
      neuronal cell line.

PMID- 16289034
TI  - The scaffold protein CNK1 interacts with the angiotensin II type 2 receptor.
AB  - The scaffold protein CNK1 mediates proliferative as well as antiproliferative
      responses including differentiation and apoptosis. The angiotensin II type 2
      (AT2) receptor belongs to the class of G protein-coupled receptors and also
      promotes antiproliferative effects. Here we report that CNK1 binds through the
      sterile alpha motif (SAM) and the conserved region in CNK (CRIC) to the AT2
      receptor. The exchange of a conserved leucine residue with arginine in the CRIC
      domain increases the binding affinity of CNK1 to the AT2 receptor. The insertion
      of a negatively charged amino acid stretch into the linker region between the N-
      and the C-terminal part of CNK1 strengthens the interaction between CNK1 and the
      AT2 receptor in a Ras-regulated manner. The biological significance of the
      interaction was supported by coprecipitation of CNK1 and the AT2 receptor in
      mouse heart extracts. Thus, CNK1 may play a role in the AT2 receptor-mediated
      signaling pathways.

PMID- 16289036
TI  - SOCS3 promotes apoptosis of mammary differentiated cells.
AB  - Growth and function of the mammary gland is regulated by cytokines and modulated
      by suppressor of cytokine signalling (SOCS) proteins. In vitro experiments
      demonstrated that SOCS3 can inhibit PRL induction of milk protein gene expression
      and STAT5 activation. We explored the SOCS3 expression pattern during mouse
      mammary development and its regulation by PRL and GH in wild-type and STAT5a-null
      mammary tissue. Our results suggest that, in vivo, PRL stimulates SOCS3
      expression in stromal adipocytes, independently of STAT5a stimulation. In mammary
      epithelial cells, SOCS3 expression appears to be related to STAT3 activation.
      Together, our results are consistent with a role of SOCS3 in the mammary gland by
      promoting apoptosis of differentiated cells (adipocytes during gestation and
      epithelial cells during involution).

PMID- 16289035
TI  - KL-6, a human MUC1 mucin, promotes proliferation and survival of lung
      fibroblasts.
AB  - The serum level of KL-6, a MUC1 mucin, is a clinically useful marker for various
      interstitial lung diseases. Previous studies demonstrated that KL-6 promotes
      chemotaxis of human fibroblasts. However, the pathophysiological role of KL-6
      remains poorly understood. Here, we further investigate the functional aspects of
      KL-6 in proliferation and apoptosis of lung fibroblasts. KL-6 accelerated the
      proliferation and inhibited the apoptosis of all human lung fibroblasts examined.
      An anti-KL-6 monoclonal antibody counteracted both of these effects induced by KL
      6 on human lung fibroblasts. The pro-fibroproliferative and anti-apoptotic
      effects of KL-6 are greater than and additive to those of the maximum effective
      concentrations of platelet-derived growth factor, basic fibroblast growth factor,
      and transforming growth factor-beta. These findings indicate that increased
      levels of KL-6 in the epithelial lining fluid may stimulate fibrotic processes in
      interstitial lung diseases and raise the possibility of applying an anti-KL-6
      antibody to treat interstitial lung diseases.

PMID- 16289037
TI  - Disruption of intermolecular disulfide bonds in PDGF-BB dimers by N-acetyl-L
      cysteine does not prevent PDGF signaling in cultured hepatic stellate cells.
AB  - Oxidative stress is important in the pathogenesis of liver fibrosis through its
      induction of hepatic stellate cell (HSC) proliferation and enhancement of
      collagen synthesis. Reactive oxygen species have been found to be essential
      second messengers in the signaling of both major fibrotic growth factors,
      platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF
      beta), in cultured HSC and liver fibrosis. The non-toxic aminothiol N-acetyl-L
      cysteine (NAC) inhibits cellular activation and attenuates experimental fibrosis
      in liver. Prior reports show that NAC is capable of reducing the effects of TGF
      beta in biological systems, in cultured endothelial cells, and HSC through its
      direct reducing activity upon TGF-beta molecules. We here analyzed the effects of
      NAC on PDGF integrity, receptor binding, and downstream signaling in culture
      activated HSC. We found that NAC dose-dependently induces disintegration of PDGF
      in vitro. However, even high doses (>20mM) were not sufficient to prevent the
      phosphorylation of the PDGF receptor type beta, extracellular signal-regulated
      kinase, or protein kinase B (PKB/Akt). Therefore, we conclude that the PDGF
      monomer is still active. The described antifibrotic effects are therefore mainly
      attributable to the structural impairment of TGF-beta signaling components
      reported previously.

PMID- 16289038
TI  - Human T lymphocytes express N-methyl-D-aspartate receptors functionally active in
      controlling T cell activation.
AB  - The aim of this study was to investigate the expression and the functional role
      of N-methyl-D-aspartate (NMDA) receptors in human T cells. RT-PCR analysis showed
      that human resting peripheral blood lymphocytes (PBL) and Jurkat T cells express
      genes encoding for both NR1 and NR2B subunits: phytohemagglutinin (PHA)-activated
      PBL also expresses both these genes and the NR2A and NR2D genes. Cytofluorimetric
      analysis showed that NR1 expression increases as a consequence of PHA (10
      microg/ml) treatment. D-(-)-2-Amino-5-phosphonopentanoic acid (D-AP5), and (+)-5
      methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine [(+)-MK 801],
      competitive and non-competitive NMDA receptor antagonists, respectively,
      inhibited PHA-induced T cell proliferation, whereas they did not affect IL-2 (10
      U/ml)-induced proliferation of PHA blasts. These effects were due to the
      prevention of T cell activation (inhibition of cell aggregate formation and CD25
      expression), but not to cell cycle arrest or death. These results demonstrate
      that human T lymphocytes express NMDA receptors, which are functionally active in
      controlling cell activation.

PMID- 16289039
TI  - Theophylline prevents NAD+ depletion via PARP-1 inhibition in human pulmonary
      epithelial cells.
AB  - Oxidative DNA damage, as occurs during exacerbations in chronic obstructive
      pulmonary disease (COPD), highly activates the nuclear enzyme poly(ADP
      ribose)polymerase-1 (PARP-1). This can lead to cellular depletion of its
      substrate NAD+, resulting in an energy crisis and ultimately in cell death.
      Inhibition of PARP-1 results in preservation of the intracellular NAD+ pool, and
      of NAD+-dependent cellular processes. In this study, PARP-1 activation by
      hydrogen peroxide decreased intracellular NAD+ levels in human pulmonary
      epithelial cells, which was found to be prevented in a dose-dependent manner by
      theophylline, a widely used compound in the treatment of COPD. This enzyme
      inhibition by theophylline was confirmed in an ELISA using purified human PARP-1
      and was found to be competitive by nature. These findings provide new mechanistic
      insights into the therapeutic effect of theophylline in oxidative stress-induced
      lung pathologies.

PMID- 16289040
TI  - Identification of tick periviscerokinin, the first neurohormone of Ixodidae:
      single cell analysis by means of MALDI-TOF/TOF mass spectrometry.
AB  - The first peptidergic neurohormone from the ticks Ixodes ricinus and Boophilus
      microplus has been identified by using a combination of immunocytochemistry and
      mass spectrometric analysis of single cells. The novel peptide (Ixori-PVK,
      PALIPFPRV-NH2) shows a high sequence homology with members of the insect
      periviscerokinin/CAP2b peptides that in insects are involved in the regulation of
      water balance. The function of this peptide in ticks is still unknown, but these
      pests consume large amounts of blood in a single blood meal which is a challenge
      for the regulation of diuretic processes. Thus, the novel peptide may be involved
      in one of the key physiological processes in ticks. High energy collision-induced
      dissociation was successfully used to distinguish between Leu/Ile ambiguities in
      single cell preparations. This is the first successful de novo sequencing of a
      peptide from single cell preparations of arthropods.

PMID- 16289041
TI  - Recombinant soluble human Fcgamma receptor I with picomolar affinity for
      immunoglobulin G.
AB  - The ectodomain of human FcgammaRI (rsCD64) was expressed in HEK 293T cells and
      purified by immobilized-metal affinity chromatography. Binding activity to human
      IgG was verified by ELISA and the isotype-specificity determined by a surface
      plasmon resonance inhibition assay was found to be the same as for native CD64.
      The active concentration of the rsCD64 preparation was derived using a solution
      competition assay and was used for the subsequent kinetic analysis. Binding
      curves were well described by a simple monovalent interaction model confirming
      the known stoichiometry of the interaction. Mass-transport limitation was
      prevented by using sufficiently low surface capacities. For binding to the
      recombinant mouse/human chimeric antibody cPIPP (IgG1/kappa) a high association
      rate of k(ass)=1.7 x 10(6) (M s)(-1) and a low dissociation rate of k(diss)=1.8 x
      10(-4) s(-1) were observed. The derived dissociation equilibrium constant of
      K(D)=110 pM was significantly lower than that reported for binding to native
      FcgammaRI.

PMID- 16289042
TI  - Two Plasmodium falciparum merozoite proteins binding to erythrocyte band 3 form a
      direct complex.
AB  - Erythrocyte invasion by malaria parasites requires multiple protein interactions.
      Our earlier studies showed that erythrocyte band 3 is an invasion receptor
      binding Plasmodium falciparum merozoite surface protein 1 and 9 (MSP1, MSP9)
      existing as a co-ligand complex. In this study, we have used biochemical
      approaches to identify the binding sites within MSP1 and MSP9 involved in the co
      ligand complex formation. A major MSP9-binding site is located within the 19kDa C
      terminal domain of MSP1 (MSP1(19)). Two specific regions of MSP9 defined as
      Delta1a and Delta2 interacted with native MSP1(19). The 42 kDa domain of MSP1
      (MSP1(42)) bearing MSP1(19) in the C-terminus bound directly to both MSP9/Delta1a
      and Delta2. Thus, the regions of MSP1 and MSP9 interacting with the erythrocyte
      band 3 receptor are also responsible for assembling the co-ligand complex. Our
      evidence suggests a ternary complex is formed between MSP1, MSP9, and band 3
      during erythrocyte invasion by P. falciparum.

PMID- 16289043
TI  - Selective accumulation of alpha-tocopherol in Drosophila is associated with
      cytochrome P450 tocopherol-omega-hydroxylase activity but not alpha-tocopherol
      transfer protein.
AB  - Humans and other mammals actively discriminate among the various forms of vitamin
      E to selectively retain alpha-tocopherol, but the phylogenetic breadth of this
      trait is unknown. We sought to determine if the fruit fly, Drosophila
      melanogaster, similarly discriminates and if so by what mechanism. Larvae and
      adult flies fed diets containing predominantly gamma- and delta-tocopherols were
      enriched in alpha-tocopherol. Inclusion in the diet of piperonyl butoxide (PBO),
      an insect cytochrome P450 inhibitor and inhibitor of tocopherol-omega-hydroxylase
      activity, greatly elevated tissue levels of delta-tocopherol but not alpha
      tocopherol. Drosophila microsomes exhibited tocopherol-omega-hydroxylase activity
      in the order of delta-T > gamma-T >> alpha-T, a pattern consistent with the
      effect of PBO in vivo. To determine if selectivity involved alpha-tocopherol
      transfer protein (alpha-TTP), adult flies were fed an equimolar mixture of d3-RRR
      and d6-all-racemic alpha-tocopherol. Flies exhibited a d3/d6 ratio of 1.03,
      demonstrating an inability to discriminate on the basis of phytyl tail
      stereochemistry, a hallmark of alpha-TTP activity. We conclude that Drosophila
      preferentially accumulates alpha-tocopherol via a mechanism involving cytochrome
      P450 tocopherol-omega-hydroxylase-mediated catabolism of other tocopherols, but
      not a mammalian-like alpha-TTP. The selective pressure favoring this trait and
      its remarkable conservation from insects to humans requires elucidation.

PMID- 16289044
TI  - Cigarette smoke extract induces changes in growth and gene expression of
      Saccharomyces cerevisiae.
AB  - The response of Saccharomyces cerevisiae cells to an aqueous extract of cigarette
      smoke was studied. Exposure to cigarette smoke extract inhibits yeast growth and
      results in global changes in gene expression spanning many functional classes of
      genes. Genes involved in response to oxidative stress are upregulated after a
      brief exposure to cigarette smoke extract. The effects of cigarette smoke extract
      on yeast growth can be reversed by treatment with anti-oxidants. Mutants lacking
      superoxide dismutase gene were hypersensitive to cigarette smoke exposure. YAP1
      is a central transcriptional regulator of oxidative stress in yeast. YAP1
      dependent expression of beta-galactosidase was enhanced following exposure to
      cigarette smoke. The overall agreement between our observations and the recently
      reported effects of cigarette smoke on gene expression in rodent and human cells
      suggests that yeast can be used as a model system in toxicogenomics studies for
      monitoring toxic agents and studying the cellular and molecular consequences of
      exposure to potentially toxic agents.

PMID- 16289045
TI  - Choroidal innervation in primate eyes.
AB  - Arteries and arterioles of the choroid are surrounded by numerous nerve fibers
      staining for nitric oxide synthase (NOS) and vasoactive intestinal peptide (VIP).
      In most mammalian eyes these nerve fibers derive from the pterygopalatine
      ganglion via the facial nerve. Stimulation of the facial nerve causes
      vasodilation of the choroidal vasculature. In primates with a well developed
      fovea centralis there are ganglion cells in the choroidal stroma which in human
      eyes amount to around 2000. The postganglionic nerve fibers of these choroidal
      ganglion cells (CGC) join the perivascular nerve fiber plexus. The CGC stain for
      NOS and VIP like the nerve cells within the pterygopalatine ganglion. There are,
      however, differences between the two cell populations. Immunohistochemical and
      ultrastructural classification of the CGC show that in addition to NOS and VIP
      almost half of the cells stain for calretinin, single ones for neuropeptide Y
      (NPY) and galanin. A number of cells is in close contact with numerous boutons
      staining for nNOS, VIP, NPY, tyrosine hydroxylase (TH), vesicular monoaminergic
      transporter (VMAT)2, vesicular acetylcholine transporter (VACHT), calretinin, and
      NPY. These data indicate a more complex integrative function of CGCs e.g. volume
      regulation in parallel with ciliary muscle contraction during accommodation.
      Ultrastructural and immunohistochemical studies indicate, that CGCs in addition
      may have mechanosensory properties. Whether they are involved in volume
      regulatory functions independent of accommodation is not yet known. In glaucoma
      disease the number of CGCs is significantly reduced. This holds true for eyes
      with primary open angle glaucoma, pseudoexfoliation glaucoma and experimentally
      induced monkey glaucoma indicating that elevated IOP is involved in the
      pathogenesis of glaucomatous CGC-degeneration.

PMID- 16289046
TI  - Microvilli defects in retinas of ezrin knockout mice.
AB  - Ezrin, a member of the ezrin/moesin/radixin (ERM) family, localizes to microvilli
      of epithelia in vivo, where it functions as a bridge between actin filaments and
      plasma membrane proteins. In the eye, ezrin has been localized to both apical
      microvilli of Muller cells and retinal pigment epithelium (RPE) apical microvilli
      and basal infoldings. In the present study, we analyze these structures in the
      eyes of early postnatal ezrin knockout mice. This analysis indicates that the
      loss of ezrin leads to substantial reductions in the apical microvilli and basal
      infoldings in RPE cells and in the Muller cell apical microvilli. The absence of
      apical microvilli in the RPE is accompanied by the presence of microvilli-like
      inclusions (MIs) in the RPE cytoplasm. Finally, photoreceptors in the ezrin
      knockout animals show substantial retardation in development as compared to their
      wild type littermates.

PMID- 16289047
TI  - Alterations in human trabecular meshwork cell homeostasis by selenium.
AB  - Epidemiological evidence indicates that selenium supplementation may increase
      risk for glaucoma and ocular hypertension. The purpose of this study was to
      determine the effects of selenium on trabecular meshwork cells, a likely site of
      pathology for glaucoma. Human trabecular meshwork (HTM) cells and human umbilical
      vein endothelial cells (HUVECs) were treated with selenium (MSeA) at or near
      physiologically relevant concentrations. Selenium uptake by cells was monitored
      using mass spectrometry. Alterations in protein secretion, intracellular
      signaling, and cell morphology were monitored; and the role of integrin signaling
      in MSeA-induced morphological alterations was investigated using divalent cation
      treatments. Radiolabeling was used to assess protein synthesis and secretion,
      while luciferase and MTT assays monitored total cellular ATP and cell viability,
      respectively. Whereas detectible changes in intracellular selenium were observed
      after exposure to 1-10 microM MSeA for 24hr, the majority remained in the
      conditioned medium. Selenium-induced morphological changes (< or =3 hr) occurred
      before alterations in protein secretion and intracellular signaling (3-6 hr).
      Zinc treatment prevented selenium-mediated alterations in protein secretion and
      changes in cell-matrix adhesion. MSeA treatment (5 microM) led to a 60% decrease
      in protein synthesis after 3 hr and a 30% reduction in secretion, although
      significant alterations in cell viability and total ATP were not observed after
      MSeA treatment. Selenium altered several indicators of HTM cell homeostasis, but
      did not affect viability at physiologically relevant doses. Similar results with
      HUVECs have implications for understanding selenium's mechanisms of action as an
      anti-angiogenic agent.

PMID- 16289049
TI  - Chronic topical administration of WIN-55-212-2 maintains a reduction in IOP in a
      rat glaucoma model without adverse effects.
AB  - Glaucoma, one of the leading causes of blindness, is associated with high
      intraocular pressure (IOP) as a risk factor. The aim of this study was to examine
      both local and systemic effects of chronic topical administration of the
      synthetic CB1/CB2 agonist, WIN-55-212-2 and its potential to sustain ocular
      hypotension. WIN-55-212-2 (0.5%) or Tocrisolve, the vehicle, was administered
      topically three times daily to rats with surgically created glaucoma for 4 weeks,
      followed by a 1-week washout period. IOP, blood pressure and heart rate were
      measured weekly along with confocal microscopy and slit lamp biomicroscopy to
      detect ocular toxicity. IOP decreased rapidly by up to 47% in the WIN-55-212-2
      treated group from 14.1+/-0.7 to 6.6+/-0.2 mmHg. The decrease was maintained
      during the treatment period. After the washout period, IOP (12.3+/-0.2 mmHg) was
      not different from baseline. In the contralateral eye, IOP showed a downward
      trend. Tocrisolve alone had no effect on IOP. No changes in blood pressure, heart
      rate or indicators of ocular toxicity were noted within either group. Topical
      application of WIN-55-212-2 significantly deceased IOP for duration of treatment.
      The decrease was sustained without the development of tolerance. Following
      cessation of therapy, IOP rapidly returned to baseline. No significant
      cardiovascular effects or ocular toxicity were noted during chronic topical
      therapy with either drug or vehicle.

PMID- 16289048
TI  - Characterization of the Felix domesticus (cat) glaucoma-associated protein
      myocilin.
AB  - The domestic cat (Felix domesticus) is a useful model for understanding the
      implications of long-term expression and function of normal and mutant myocilin.
      To better understand the role myocilin has in the cat eye, we isolated and
      characterized cat myocilin. Oligonucleotides designed against conserved
      nucleotide regions of myocilin mammalian orthologs were used to PCR amplify a
      partial cat myocilin cDNA clone. Rapid amplification of cDNA ends (5' and 3'
      RACE) was used to obtain full-length cat myocilin. The 2125 nucleotide cat
      myocilin cDNA contains a 490 amino acid open reading frame. Comparison of cat
      myocilin to human myocilin shows a 87% similarity, including conservation of the
      N-terminal leucine zipper, N-linked glycosylation site, C-terminal olfactomedin
      domain, and all five cysteine residues thought to be involved in disulfide bond
      formation. Expression in a transformed human trabecular cell line or in Crandall
      feline kidney cells showed cat myocilin was secreted from these cells, similar to
      human myocilin, suggesting cat myocilin contains a functional signal peptide
      sequence. In contrast, expression of cat myocilin containing a known human
      glaucoma-associated mutation (Y423H in cat; Y437H in human) was not secreted.
      Characterization of cat myocilin will enable long-term studies be performed in
      Felix domesticus to analyze changes to intraocular pressure and the aqueous
      outflow pathway following expression of myocilin and glaucoma causing mutations.

PMID- 16289050
TI  - Mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K)
      pathways differently regulate retinal pigment epithelial cell-mediated collagen
      gel contraction.
AB  - Retinal pigment epithelial (RPE) cell-mediated extracellular matrix contraction
      is believed to contribute to developing proliferative vitreoretinopathy. It has
      been shown that platelet-derived growth factor (PDGF) and its intracellular
      signaling pathway, including mitogen-activated protein kinase (MAPK) and
      phosphatidylinositol-3 kinase (PI3K), are mainly involved in this process. The
      aim of this study is to investigate how these downstream signaling pathways are
      related to RPE-mediated collagen gel contraction. We performed the gel
      contraction assay to evaluate the effect of PDGF in cultured ARPE-19 cells under
      the presence or absence of PD98059, MAPK inhibitor or wortmannin, PI3K inhibitor.
      Experiments treated with neutralizing antibody for various subtypes of integrin
      were also performed and the effect on PDGF-induced gel contraction was
      investigated. Expression changes of integrin alpha1, alpha2 and beta1 after PDGF
      stimulation was evaluated using quantitative real-time PCR and flow cytometry.
      The results showed that PDGF up-regulated ARPE-19 cell-mediated gel contractile
      activity. PDGF-induced collagen gel contraction was attenuated under presence of
      PD98059, wortmannin, or neutralizing antibody for integrin alpha1, alpha2, or
      beta1, all of which are critical subset for binding with type I collagen. The
      expression of integrin alpha1 and alpha2 was increased after PDGF stimulation in
      both real-time PCR and flow cytometry, however beta1 expression was not
      increased. PD98059 significantly attenuated integrin alpha1 and alpha2
      expressions. However, wortmannin did not have the same effect. In conclusion,
      PDGF promotes ARPE-19 cell-mediated gel contraction via both MAPK and PI3K. This
      was probably due to an increased expression of integrin alpha1 and alpha2, which
      is mediated by MAPK, but not by PI3K. PI3K may regulate collagen gel contraction
      by another mechanism other than the up-regulation of integrin expression.

PMID- 16289051
TI  - Galactans from cystocarpic plants of the red seaweed Callophyllis variegata
      (Kallymeniaceae, Gigartinales).
AB  - The polysaccharide extracted from cystocarpic Callophyllis variegata was
      fractionated with potassium chloride yielding three small fractions that
      precipitated in the ranges of 0-0.05 M KCl, 1.20-1.25 M KCl, and 1.80-2.00 M KCl,
      and a main product soluble in 2.00 M KCl. These fractions were analyzed, and as
      the first one contained very high amounts of protein, it was not studied further.
      Structural analysis of the rest of the fractions (F1-F3) was carried out by
      methylation, desulfation-methylation, IR, and 13C NMR spectroscopy. The results
      are consistent for F1 with a carrageenan-type backbone mainly constituted by beta
      D-galactose 2-sulfate linked to alpha-D-galactose 2,3,6-trisulfate and beta-D
      galactose 2,4-disulfate linked to 3,6-anhydro-D-galactose 2-sulfate as dominant
      diads. In F2 these diads are present together with low amounts of beta-D
      galactose 2-sulfate linked to 3,6-anhydro-D-galactose 2-sulfate, whose
      contribution becomes higher in F3. In addition, minor but significant amounts of
      L-galactose were detected. F1-F3 showed potent antiviral activity against herpes
      simplex types 1 and 2 and dengue type 2.

PMID- 16289052
TI  - Improved sciatic nerve regeneration by local thyroid hormone treatment in adult
      rat is accompanied by increased expression of SCG10.
AB  - Thyroid hormone plays an important role in regulating the development and
      regeneration of the nervous system. Our previous work showed that local
      administration of triiodothyronine (T3) at the level of transected rat sciatic
      nerve increased the number and diameter of regenerated axons, but the mechanism
      underlying the improved regeneration is still unclear. Here, we have investigated
      the effect of T3 on the expression of SCG10, a regulator of microtubule dynamics
      in growth cones. After transection of adult rat sciatic nerves, silicone tubes
      were implanted and filled with T3 or phosphate-buffered solution. At various time
      points following surgery, the expression of SCG10 protein and mRNA was analyzed.
      Semi-quantitative Western blot analysis revealed that sciatic nerve transection
      induced a more than 20-fold upregulation of SCG10 protein in proximal nerve
      segments at 1 day post-lesion, while at this time point, SCG10 mRNA in dorsal
      root ganglion neurons was not increased yet. The increase in SCG10 protein and
      mRNA could be observed over 30 days. Local T3 treatment significantly enhanced
      the increase in SCG10 protein levels about two-fold in the different segments of
      transected nerve during the regeneration period. Also SCG10 mRNA levels in lumbar
      ganglia were enhanced. Immunohistochemical analysis showed that T3 treatment not
      only increased the number of SCG10 positive axons but also the intensity of their
      staining. These results suggest that SCG10 is involved in the regulation of
      regeneration. The stimulating effect of T3 on SCG10 expression could provide a
      mechanism by which T3 enhances peripheral nerve regeneration.

PMID- 16289053
TI  - Intra-operative STN DBS attenuates the prominent beta rhythm in the STN in
      Parkinson's disease.
AB  - Power spectra from local field potentials (LFPs) recorded post-operatively from
      the deep brain stimulation (DBS) macroelectrode show prominence of the beta
      rhythm (11-30 Hz) in untreated Parkinson's disease (PD). Dopaminergic medication
      and movement attenuate this beta band in PD. In this pilot study of six sides in
      four patients, we recorded LFPs from the DBS electrode in untreated PD patients
      in the operating room. In all cases, there was a peak in the time-frequency
      spectrogram in the beta frequency range when the patients were at rest, which was
      associated with attenuation in the same range with movement. The actual frequency
      range and the strength of the beta peak varied among cases. In two patients,
      intra-operative constraints permitted recording of LFPs at rest, before and
      immediately after subthalamic nucleus (STN) DBS. In both patients we documented
      that STN DBS caused a significant attenuation in power in the beta band at rest
      that persisted for 15-25 s after DBS had been turned off (P < 0.01). From one
      case, our data suggest that the beta rhythm attenuation was most prominent within
      the STN itself. This study shows for the first time that STN DBS attenuates the
      power in the prominent beta band recorded in the STN of patients with PD. These
      pilot findings raise the interesting possibility of using this biomarker for
      closed loop DBS or neuromodulation.

PMID- 16289054
TI  - NMDA receptor-mediated epileptiform persistent activity requires calcium release
      from intracellular stores in prefrontal neurons.
AB  - Various normal and pathological forms of synchronized population activity are
      generated by recurrent excitation among pyramidal neurons in the neocortex.
      However, the intracellular signaling mechanisms underlying this activity remain
      poorly understood. In this study, we have examined the cellular properties of
      synchronized epileptiform activity in the prefrontal cortex with particular
      emphasis on a potential role of intracellular calcium stores. We find that the
      zero-magnesium-induced synchronized activity is blocked by inhibition of sarco
      endoplasmic reticulum Ca(2+)-ATPases, phospholipase C (PLC), the inositol 1,4,5
      trisphosphate (IP3) receptor, and the ryanodine receptor. This same activity is,
      however, not affected by application of metabotropic glutamatergic receptor
      (mGluR) agonists, nor by introduction of an mGluR antagonist. These results
      suggest that persistent synchronized activity in vitro is dependent upon calcium
      release from internal calcium stores through the activation of PLC-IP3 receptor
      pathway. Our findings also raise the possibility that intracellular calcium
      release may be involved in the generation of pathologic synchronized activity in
      epilepsy in vivo and in physiological forms of synchronized cortical activity.

PMID- 16289055
TI  - Engagement of PSGL-1 upregulates CSF-1 transcription via a mechanism that may
      involve Syk.
AB  - PSGL-1, the optimal selectin ligand demonstrated by in vivo studies to date, is
      an essential adhesive molecule mediating the rolling of leukocytes on the
      endothelial cells and the recruitment of leukocytes to the inflamed tissue.
      Recent studies demonstrated, in addition to its direct role in capture of
      leukocytes from the bloodstream, PSGL-1 also functions as a signal-transducing
      receptor and initiates a series of intracellular signal events during the
      activation of leukocytes. Our present work showed antibody engagement of PSGL-1
      upregulated the transcriptional activity of CSF-1 promotor and increased the
      endogenous expression of CSF-1 mRNA in Jurkat cell. Overexpression of wild-typed
      non-receptor tyrosine kinase Syk, but not kinase dead mutant of Syk, promoted the
      upregulation of the transcriptional activity of CSF-1 promoter caused by antibody
      engagement of PSGL-1. Additionally, special inhibitor of Syk Piceatannol
      suppressed the increase of CSF-1 mRNA caused by the engagement of PSGL-1. The
      results suggest that signal transducted by PSGL-1 upregulate the transcriptional
      activity of CSF-1, and non-receptor tyrosine kinase Syk participates in this
      pathway.

PMID- 16289056
TI  - Regulation of nuclear Prointerleukin-16 and p27(Kip1) in primary human T
      lymphocytes.
AB  - Prointerleukin-16 (Pro-IL-16) is an abundant, PDZ domain-containing protein
      expressed in the nucleus and cytoplasm of resting human T lymphocytes. We have
      previously shown that ectopic expression of Pro-IL-16 in Pro-IL-16-negative human
      Jurkat cells represses transcription of the F-box protein, Skp2, resulting in
      accumulation of the cyclin-dependent kinase inhibitor, p27(Kip1), and G0/G1 cell
      cycle arrest. The current studies demonstrate the kinetics of Pro-IL-16 and
      p27(Kip1) expression in activated normal human T lymphocytes. We correlate
      nuclear Pro-IL-16 loss with decreased p27(Kip1) expression, increased cell cycle
      progression, and proliferation. Conversely, we show that constitutive expression
      of Pro-IL-16 by retroviral infection of activated human T lymphocytes induces
      G0/G1 cell cycle arrest, inhibits proliferation, and is associated with increased
      levels of p27(Kip1). These findings implicate nuclear Pro-IL-16 as a cell cycle
      regulatory protein for human T lymphocytes.

PMID- 16289057
TI  - Correlation of temperature induced conformation change with optimum catalytic
      activity in the recombinant G/11 xylanase A from Bacillus subtilis strain 168
      (1A1).
AB  - The 1.7A resolution crystal structure of recombinant family G/11 beta-1,4
      xylanase (rXynA) from Bacillus subtilis 1A1 shows a jellyroll fold in which two
      curved beta-sheets form the active-site and substrate-binding cleft. The onset of
      thermal denaturation of rXynA occurs at 328 K, in excellent agreement with the
      optimum catalytic temperature. Molecular dynamics simulations at temperatures of
      298-328 K demonstrate that below the optimum temperature the thumb loop and palm
      domain adopt a closed conformation. However, at 328 K these two domains separate
      facilitating substrate access to the active-site pocket, thereby accounting for
      the optimum catalytic temperature of the rXynA.

PMID- 16289058
TI  - A problem in multivariate analysis of codon usage data and a possible solution.
AB  - Multivariate analyses are often used to identify major trends of variation in
      synonymous codon usage among genes. These analyses need to be performed on
      properly normalized codon usage data to avoid biases masking this synonymous
      variation, i.e., gene length, amino acid usage, and codon degeneracy; however,
      previous studies have failed to do so. In this paper, we demonstrate that the use
      of alternative normalized data (called 'relative adaptiveness' in the literature)
      can avoid all these biases and furthermore, can identify more trends of variation
      among genes, including GC-ending codon usage, GT-ending codon usage, and gene
      expression level.

PMID- 16289059
TI  - Regulation of vascular smooth muscle cell proliferation, migration and death by
      heparan sulfate 6-O-endosulfatase1.
AB  - Migration, proliferation and death of vascular smooth muscle cells (VSMC) are
      important events in vascular pathology regulated by heparan sulfate proteoglycans
      and hence potentially by cell surface HS 6-O-endosulfatase1 (sulf1). Sulf1 mRNA
      expression was increased in cultured VSMC compared to rat aorta. Furthermore,
      adenovirus mediated overexpression of quail sulf1 decreased adhesion, and
      increased proliferation and apoptosis of VSMC. Overexpression of a dominant
      negative variant also decreased adhesion of VSMC and increased proliferation,
      apoptosis, migration and chemotaxis of VSMC. Our results imply that only normal
      levels of 6-O-sulfation maintained by sulf1 are optimal for several functions of
      VSMC.

PMID- 16289060
TI  - Subclinical hypervitaminosis A in rat: measurements of bone mineral density (BMD)
      do not reveal adverse skeletal changes.
AB  - We have previously shown that subclinical hypervitaminosis A in rats causes
      fragile bones. To begin to investigate possible mechanisms for Vitamin A action
      we extended our previous study. Forty-five mature female Sprague-Dawley rats were
      divided into three groups, each with 15 animals. They were fed a standard diet
      containing 12IU Vitamin A per g pellet (control, C), or a standard diet
      supplemented with 120 IU ("10xC") or 600 IU ("50xC") Vitamin A/g pellet for 12
      weeks. At the end of the study, serum retinyl esters were elevated 4- and 20
      fold. Although neither average food intake nor final body weights were
      significantly different between groups, a dose-dependent reduction in serum
      levels of Vitamin D and E, but not Vitamin K, was found. In the 50xC-group the
      length of the humerus was the same as in controls, but the diameter was reduced (
      4.1%, p<0.05). Peripheral quantitative computed tomography (pQCT) at the
      diaphysis showed that bone mineral density (BMD) was unchanged and that
      periosteal circumference had decreased significantly (-3.7%, p<0.05). Ash weight
      of the humerus was not affected, but since bone volume decreased, volumetric BMD,
      as measured by the bone ash method, even increased (+2.5%, p<0.05). In
      conclusion, interference with other fat-soluble Vitamins is a possible indirect
      mechanism of Vitamin A action. Moreover, BMD measurements do not reveal early
      adverse skeletal changes induced by moderate excesses of Vitamin A in rats. Since
      the WHO criterium for osteoporosis is based on BMD, further studies are warranted
      to examine whether this is also true in humans.

PMID- 16289061
TI  - Interactions of organophosphorus and related compounds with cholinesterases, a
      theoretical study.
AB  - Acetylcholinesterase (AChE) is an interesting research target not only because of
      its high enzyme catalytic rate but also because of the wide range of health
      effects resulting from its inhibition. This paper discusses results of a
      theoretical study of acetylcholinesterase inhibition using several simulation
      techniques. In the first technique, a novel method was developed and used for
      predicting the binding affinity of human AChE (huAChE) inhibitors. Results are
      also presented for classical molecular dynamics and quantum mechanical
      simulations. Theoretical proton NMR shift results are obtained and compared to
      experiment, and the importance of the Glu199 residue is discussed in the context
      of the model.

PMID- 16289062
TI  - Acetylcholinesterase (AChE) gene modification in transgenic animals: functional
      consequences of selected exon and regulatory region deletion.
AB  - AChE is an alternatively spliced gene. Exons 2, 3 and 4 are invariantly spliced,
      and this sequence is responsible for catalytic function. The 3' alternatively
      spliced exons, 5 and 6, are responsible for AChE disposition in tissue [J.
      Massoulie, The origin of the molecular diversity and functional anchoring of
      cholinesterases. Neurosignals 11 (3) (2002) 130-143; Y. Li, S. Camp, P. Taylor,
      Tissue-specific expression and alternative mRNA processing of the mammalian
      acetylcholinesterase gene. J. Biol. Chem. 268 (8) (1993) 5790-5797]. The splice
      to exon 5 produces the GPI anchored form of AChE found in the hematopoietic
      system, whereas the splice to exon 6 produces a sequence that binds to the
      structural subunits PRiMA and ColQ, producing AChE expression in brain and
      muscle. A third alternative RNA species is present that is not spliced at the 3'
      end; the intron 3' of exon 4 is used as coding sequence and produces the read
      through, unanchored form of AChE. In order to further understand the role of
      alternative splicing in the expression of the AChE gene, we have used homologous
      recombination in stem cells to produce gene specific deletions in mice.
      Alternatively and together exon 5 and exon 6 were deleted. A cassette containing
      the neomycin gene flanked by loxP sites was used to replace the exon(s) of
      interest. Tissue analysis of mice with exon 5 deleted and the neomycin cassette
      retained showed very low levels of AChE expression, far less than would have been
      anticipated. Only the read-through species of the enzyme was produced; clearly
      the inclusion of the selection cassette disrupted splicing of exon 4 to exon 6.
      The selection cassette was then deleted in exon 5, exon 6 and exons 5 + 6 deleted
      mice by breeding to Ella-cre transgenic mice. AChE expression in serum, brain and
      muscle has been analyzed. Another AChE gene targeted mouse strain involving a
      region in the first intron, found to be critical for AChE expression in muscle
      cells [S. Camp, L. Zhang, M. Marquez, B. delaTorre, P. Taylor, Knockout mice with
      deletions of alternatively spliced exons of Acetylcholinesterase, in: N.C.
      Inestrosa, E.O. Campus (Eds.), VII International Meeting on Cholinesterases,
      Pucon-Chile Cholinesterases in the Second Millennium: Biomolecular and
      Pathological Aspects. P. Universidad Catholica de Chile-FONDAP Biomedicina, 2004,
      pp. 43-48; R.Y.Y. Chan, C. Boudreau-Lariviere, L.A. Angus, F. Mankal, B.J.
      Jasmin, An intronic enhancer containing an N-box motif is required for synapse-
      and tissue-specific expression of the acetylcholinesterase gene in skeletal
      muscle fibers. Proc. Natl. Acad. Sci. USA 96 (1999) 4627-4632], is also
      presented. The intronic region was floxed and then deleted by mating with Ella
      cre transgenic mice. The deletion of this region produced a dramatic phenotype; a
      mouse with near normal AChE expression in brain and other CNS tissues, but no
      AChE expression in muscle. Phenotype and AChE tissue activities are compared with
      the total AChE knockout mouse [W. Xie, J.A. Chatonnet, P.J. Wilder, A. Rizzino,
      R.D. McComb, P. Taylor, S.H. Hinrichs, O. Lockridge, Postnatal developmental
      delay and supersensitivity to organophosphate in gene-targeted mice lacking
      acetylcholinesterase. J. Pharmacol. Exp. Ther. 293 (3) (2000) 896-902].

PMID- 16289063
TI  - Host-regulated disposition of mammalian AChEs.
AB  - Primates are characterized by a paucity of soluble acetylcholinesterase (AChE) in
      the circulation at the adult stage, where the predominant circulating
      cholinesterase is butyrylcholinesterase. In recent years, we subjected
      recombinant human and bovine acetylcholinesterase to extensive pharmacokinetic
      studies in mice, an animal system which also displays very low levels of
      circulating AChE. In this system, a post-translation-related hierarchical pattern
      governing circulatory residence through AChE sialylation, subunit tetramerization
      and glycan loading was elucidated. Based on these studies, coordinated modulation
      of the sialic acid contents, state of subunit assembly and number of glycans
      allowed us to generate human or bovine AChE forms which reside in the circulation
      of mice for long periods of time, mimicking the pharmacokinetic behavior of
      native serum-derived cholinesterases. However, extension of the pharmacokinetic
      studies to primates, revealed an additional element, which affects circulatory
      residence of AChEs in this animal system. Unlike in the case of bovine AChE,
      optimization of subunit assembly and glycan loading of the primate versions of
      AChE (human or rhesus) did not increase their circulatory lifetime in rhesus
      macaques. This differential pharmacokinetic behavior of bovine and primate AChEs
      in macaques appears to be related to the 35 diverging bovine/primate AChE amino
      acids which are clustered within three defined domains at the enzyme surface, and
      thereby may facilitate the specific removal of "self" or "self-like"
      cholinesterases from the circulation of monkeys and thus provide an explanation
      for the absence of soluble AChE in the circulation of primates.

PMID- 16289064
TI  - Protection against soman or VX poisoning by human butyrylcholinesterase in guinea
      pigs and cynomolgus monkeys.
AB  - Human butyrylcholinesterase (HuBuChE), purified from outdated human plasma, is
      being evaluated for efficacy against nerve agents in guinea pigs and cynomolgus
      monkeys. Previous studies in rodents and nonhuman primates demonstrated that
      pretreatment of animals with enzymes that can scavenge nerve agents could provide
      significant protection against behavioral and lethal effects of nerve agent
      intoxication. In preparation for evaluation of efficacy of HuBuChE prior to
      initiating an investigational new drug (IND) application, the pharmacokinetics of
      HuBuChE were evaluated in guinea pigs and in cynomolgus monkeys. HuBuChE was
      injected intramuscularly (i.m.) at two doses, and blood samples were taken to
      follow the time-course of HuBuChE in blood for up to 168 h after administration.
      In guinea pigs, the two doses of HuBuChE, 19.9 and 32.5 mg/kg, produced similar
      times of maximal blood concentration (T(max) of 26.0 and 26.8 h, respectively)
      and similar elimination half-times (t(1/2) of 64.6 and 75.5 h, respectively).
      Enzyme levels were still 10-fold over baseline at 72 h. Based on these data,
      guinea pigs were administered 150 mg/kg of enzyme i.m. and challenged at T(max).
      Soman or VX doses were approximately 1.5, 2.0 and 2.0 x LD50 administered
      subcutaneously (s.c.) in sequence at 90-120 min apart. None of the animals
      displayed signs of organophosphorus (OP) anticholinesterase intoxication at any
      of the challenge levels, and all survived for the 14-day duration of the
      experiment. Similar experiments were carried out with cynomolgus monkeys to
      determine the pharmacokinetics of HuBuChE and its efficacy against soman. The
      complete survival of nearly all animals tested to date, coupled with the maximal
      blood concentration and half-life elimination profile obtained for HuBuChE after
      i.m. injection, provides strong support for the continued development of HuBuChE
      as a product to protect against nerve agents.

PMID- 16289065
TI  - A modified grounded theory study of how psychiatric nurses work with suicidal
      people.
AB  - BACKGROUND: People with mental health problems continue to present a
      disproportionately high risk of suicide. Despite the relevance of suicide to
      psychiatric/mental health (P/MH) nurses, there is a documented paucity of
      research in this substantive area undertaken by or referring specifically to P/MH
      nurses; there is currently no extant theory to guide P/MH nursing care of the
      suicidal person. OBJECTIVES: Accordingly, this paper reports on a study
      undertaken to determine if P/MH nurses provide meaningful caring response to
      suicidal people, and if so how. DESIGN: The study used a modified grounded theory
      method and was conducted in keeping with the Glaserian tenets of Grounded Theory.
      SETTINGS: The study was conducted in two geographical locations within the United
      Kingdom, one in the North and the other in the Midlands; both locations contained
      large urban centres. PARTICIPANTS: A total of 20 participants were selected
      across the locations by means of theoretical sampling. All the participants were
      over 18 years old, had made a serious attempt on their lives or felt they were on
      the cusp of so doing and had received 'crisis' care from the 'emergency'
      psychiatric services. METHODS: The study adhered to the principle features of
      Glaserian grounded theory namely-(a) theory generation, not theory verification;
      (b) theoretical sampling, (c) the constant comparative method of data analysis;
      and (d) theoretical sensitivity (searching for/discovering the core variable, one
      which identified the key pychosocial process and contains temporal dimensions
      stages). Further, the authors ensured that the study was concerned with
      generating conceptual theory, not conceptual description. FINDINGS/CONCLUSION:
      The findings indicate that this key psychosocial problem is addressed through the
      core variable, 're-connecting the person with humanity'. This parsimonious theory
      describes and explains a three-stage healing process consisting of the sub-core
      variables: 'reflecting an image of humanity', 'guiding the individual back to
      humanity' and 'learning to live'.

PMID- 16289066
TI  - From semantics to syntax and back again: argument structure in the third year of
      life.
AB  - An essential part of the human capacity for language is the ability to link
      conceptual or semantic representations with syntactic representations. On the
      basis of data from spontaneous production, suggested that young children acquire
      such links on a verb-by-verb basis, with little in the way of a general
      understanding of linguistic argument structure. Here, we suggest that a receptive
      understanding of argument structure--including principles linking syntax and
      conceptual/semantic structure--appears earlier. In a forced-choice pointing task
      we have shown that toddlers in the third year of life can map a single scene
      (involving a novel causative action paired with a novel verb) onto two distinct
      syntactic frames (transitive and intransitive). This suggests that even before
      toddlers begin generalizing argument structure in their own speech, they have
      some representation of conceptual/semantic categories, syntactic categories, and
      a system that links the two.

PMID- 16289067
TI  - Cross-modal interactions in the perception of musical performance.
AB  - We investigate the dynamics of sensory integration for perceiving musical
      performance, a complex natural behavior. Thirty musically trained participants
      saw, heard, or both saw and heard, performances by two clarinetists. All
      participants used a sliding potentiometer to make continuous judgments of tension
      (a measure correlated with emotional response) and continuous judgments of
      phrasing (a measure correlated with perceived musical structure) as performances
      were presented. The data analysis sought to reveal relations between the sensory
      modalities (vision and audition) and to quantify the effect of seeing the
      performances on participants' overall subjective experience of the music. In
      addition to traditional statistics, functional data analysis techniques were
      employed to analyze time-varying aspects of the data. The auditory and visual
      channels were found to convey similar experiences of phrasing but different
      experiences of tension through much of the performances. We found that visual
      information served both to augment and to reduce the experience of tension at
      different points in the musical piece (as revealed by functional linear modeling
      and functional significance testing). In addition, the musicians' movements
      served to extend the sense of phrasing, to cue the beginning of new phrases, to
      indicate musical interpretation, and to anticipate changes in emotional content.
      Evidence for an interaction effect suggests that there may exist an emergent
      quality when musical performances are both seen and heard. The investigation
      augments knowledge of human communicative processes spanning language and music,
      and involving multiple modalities of emotion and information transfer.

PMID- 16289068
TI  - Unconscious inhibition and facilitation at the objective detection threshold:
      replicable and qualitatively different unconscious perceptual effects.
AB  - Although the veridicality of unconscious perception is increasingly accepted,
      core issues remain unresolved [Jack, A., & Shallice, T. (2001). Introspective
      physicalism as an approach to the science of consciousness. Cognition, 79, 161
      196], and sharp disagreement persists regarding fundamental methodological and
      theoretical issues. The most critical problem is simple but tenacious-namely, how
      to definitively rule out weak conscious perception as an alternative explanation
      for putatively unconscious effects. Using a direct task and objectively
      undetectable stimuli, the current experiments demonstrate clearly reliable
      unconscious perceptual effects, which differ qualitatively from weakly conscious
      effects in fundamental ways. Most importantly, the current effects correlate
      negatively with stimulus detectability, directly rebutting the exhaustiveness,
      null sensitivity, and exclusiveness problems [Reingold, E., & Merikle, P. (1988).
      Using direct and indirect measures to study perception without awareness.
      Perception & Psychophysics, 44, 563-575; Reingold, E., & Merikle, P. (1990). On
      the inter-relatedness of theory and measurement in the study of unconscious
      processes. Mind and Language, 5, 9-28)], which all predict positive correlations.
      Moreover, the current effects are entirely bidirectional [Katz, (2001).
      Bidirectional experimental effects. Psychological Methods, 6, 270-281)] and
      radically uncontrollable, including below-chance performance despite intentions
      to facilitate. In contrast, weakly conscious effects on direct measures are
      unidirectional, facilitative, and potentially controllable. Moreover, these
      qualitative differences also suggest that objective and subjective threshold
      phenomena are fundamentally distinct, rather than the former simply being a
      weaker version of the latter [Merikle, P., Smilek, D., Eastwood, J. (2001).
      Perception without awareness: Perspectives from cognitive psychology. Cognition,
      79, 115-134]. Accordingly, it is important to distinguish between rather than
      conflate these methods. Further, the current effects reinforce recent work [e.g.
      Naccache, L., Blandin, E., & Dehaene, S. (2002). Unconscious masked priming
      depends on temporal attention. Psychological Science, 13, 416-424] demonstrating
      that unconscious effects, although not selectively controllable, are nonetheless
      mediated by strategic and individual difference factors, rather than being immune
      to such influences as long thought.

PMID- 16289069
TI  - Thematic role properties of subjects and objects.
AB  - This paper tests two claims about the thematic roles Agent and Patient: first,
      that they can be decomposed into more primitive features, as laid out in Dowty's
      (1991) Proto-Roles Hypothesis; and second, that these properties can be inferred
      directly from the grammatical roles subject and object. In Experiments 1 and 2,
      participants rated the Proto-Roles properties of the subject and object of
      transitive sentences with real verbs. Subjects were rated as more Agent-like than
      objects, while objects were rated as more Patient-like than subjects. Experiment
      3 used transitive sentences with nonsense content words (e.g. "The rom mecked the
      zarg"). Even in the absence of a known verb, the results were the same.
      Experiment 4 examined the corollary prediction that subjects and objects should
      not differ on grammatically irrelevant properties (e.g. "being liquid"); this
      prediction was confirmed. In Experiment 5, verbs that do not permit objects (e.g.
      "fall," "erupt") were placed in the transitive frame. Results were the same as in
      Experiments 1 through 3. Moreover, the semantics of the verb were altered by the
      frame, indicating that participants tried to fuse the semantics of the verb with
      those of the frame. Possible sources of these inferences are considered.

PMID- 16289070
TI  - Audio-visual speech perception off the top of the head.
AB  - The study examined whether people can extract speech related information from the
      talker's upper face that was presented using either normally textured videos
      (Experiments 1 and 3) or videos showing only the outlined of the head
      (Experiments 2 and 4). Experiments 1 and 2 used within- and cross-modal matching
      tasks. In the within-modal task, observers were presented two pairs of short
      silent video clips that showed the top part of a talker's head. In the cross
      modal task, pairs of audio and silent video clips were presented. The task was to
      determine the pair in which the talker said the same sentence. Performance on
      both tasks was better than chance for the outline as well as textured
      presentation suggesting that judgments were primarily based on head movements.
      Experiments 3 and 4 tested if observing the talker's upper face would help
      identify speech in noise. The results showed the viewing the talker's moving
      upper head produced a small but reliable improvement in speech intelligibility,
      however, this effect was only secure for the expressive sentences that involved
      greater head movements. The results suggest that people are sensitive to speech
      related head movements that extend beyond the mouth area and can use these to
      assist in language processing.

PMID- 16289071
TI  - Coronary artery calcium as a measure of biologic age.
AB  - BACKGROUND: Age is assigned a heavy weight in the calculation of the total
      cardiovascular risk score but often the atherosclerotic disease burden varies
      from a patient's chronological age. METHODS: We used measures of coronary artery
      calcium to estimate the number of life years lost (calcium-adjusted age) in
      10,377 asymptomatic individuals referred for electron beam tomography (EBT)
      screening and followed for 5 years for all-cause mortality. Linear regression was
      used to calculate predicted age and time to death was estimated via a Cox
      proportional hazard model. RESULTS: There was a direct relationship between
      coronary artery calcium and observed age (r = 0.32, p < 0.0001). In linear
      prediction models, a calcium score < 10 resulted in a reduction in observed age
      by 10 years in subjects older than 70 years, while a calcium score > 400 added as
      much as 30 years of age to younger patients. Calcium-adjusted age was a better
      predictor of mortality (model chi2 = 373, p < 0.0001) than observed age (model
      chi2 = 355, p < 0.0001). Detectable calcium was noted in 16% of men and 12% of
      women with an unadjusted low risk Framingham score (p < 0.0001). For those with
      an intermediate Framingham risk score, calcium scores > 10 were noted in 31 and
      43% of men and women (p < 0.0001). Using calcium-adjustments to age, 55% of
      previously low risk Framingham scores to intermediate risk (p < 0.0001).
      Similarly, 45% of the unadjusted intermediate Framingham risk scores were re
      classified as high risk based upon calcium-adjusted ages (p < 0.0001).
      CONCLUSIONS: Measures of coronary artery calcium are related to survival and can
      be used to assess an individual's biological age. Undetected risk based upon
      current calculations of the Framingham risk may be improved based upon
      determination of a re-adjustment of a patient's age using the extent of coronary
      calcification.

PMID- 16289072
TI  - Myeloperoxidase genetic polymorphisms modulate human neutrophil enzyme activity:
      genetic determinants for atherosclerosis?
AB  - OBJECTIVE: Myeloperoxidase (MPO), an abundant leukocyte hemoprotein has been
      linked to atherosclerosis and cardiovascular disease. We previously found new
      genetic polymorphisms in MPO gene. The purpose of this study was to evaluate the
      influences of these polymorphisms on human neutrophil MPO activity by means of
      haplotype analysis. METHODS AND RESULTS: Neutrophils from 102 blood donors were
      isolated and MPO activity was measured, while subjects were genotyped for
      polymorphisms located in MPO gene 5'non-coding region (-1940A > G, -638C > A, 
      463G > A and -129G > A) and in coding region (V53F, M251T, A332V, I642L and
      I717V). Single-point analysis showed that the -638C > A and the V53F
      polymorphisms were significantly associated with MPO activity, and haplotype
      analysis confirmed that two haplotypes, one carrying the -638A allele and the
      other carrying the 53F allele, resulted an increase in MPO activity. CONCLUSION:
      Since MPO is suspected to be a bio-marker in cardiovascular disease, -638C > A
      and V53F polymorphisms associated with increased enzymatic activity could be
      genetic determinants for cardiovascular disease risk.

PMID- 16289073
TI  - Pitavastatin-induced downregulation of CCR2 and CCR5 in monocytes is associated
      with the arrest of cell-cycle in S phase.
AB  - The pleiotropic effects of statin, including its anti-inflammatory effects, via
      chemokines may be independent of statin-induced cholesterol reduction. Therefore,
      we examined the effect of pitavastatin on cell proliferation and the association
      between chemokine receptors (CCR2 and CCR5) and their ligands, RANTES (regulated
      upon activation, normal T cell-expressed and secreted) and monocyte chemotactic
      protein-1 (MCP-1), in monocytes. Pitavastatin but not pravastatin inhibited cell
      proliferation in a dose-dependent manner and showed S-phase arrest associated
      with the downregulation of CCR2 and CCR5 expression in human monocytic tumor
      cells (U937 cells). Although the anti-proliferative effects of pitavastatin were
      not inhibited by lower concentrations of RANTES and MCP-1, overexpression of
      CCR2/CCR5 significantly blocked the anti-proliferation with a low concentration
      of RANTES or MCP-1. Pitavastatin upregulated p21(waf1) but not p27(kip1), and did
      not change the expression levels of cyclin D1 or cdk4. In addition, RANTES and
      MCP-1 upregulated cyclin D1 in the presence of pitavastatin. In conclusion, the
      anti-proliferative effect of pitavastatin, but not pravastatin, through the
      downregulation of CCR2/CCR5 may be a pleiotropic effect. This effect may be anti
      atherogenic in monocytes.

PMID- 16289074
TI  - Tests of the E-Z Reader model: exploring the interface between cognition and eye
      movement control.
AB  - This paper is simultaneously a test and refinement of the E-Z Reader model and an
      exploration of the interrelationship between visual and language processing and
      eye-movements in reading. Our modeling indicates that the assumption that words
      in text are processed serially by skilled readers is a viable and attractive
      hypothesis, as it accounts not only for "normal" reading data, but also for the
      pattern of decrements that occur when text is withheld from view during certain
      periods of time, such as in the boundary paradigm and the disappearing text
      paradigm. Our analyses also indicate (a) that lexical processing during reading
      is essentially continuous and (b) that the trigger for eye movements has to be a
      different (and prior) event to the trigger for shifts of covert spatial
      attention. In addition, the parameter values in our model are in accordance with
      what is known about such processes and should be taken as serious hypotheses for
      how long these processes last. Although a parallel model may be able to duplicate
      the predictions of the E-Z Reader model, we think that it is likely to be far
      less parsimonious and not nearly as good a heuristic device for using eye
      movements to understand language processing in reading.

PMID- 16289075
TI  - Entitling art: Influence of title information on understanding and appreciation
      of paintings.
AB  - There is evidence that presenting titles together with artworks affects their
      processing. We investigated whether elaborative and descriptive titles change the
      appreciation and understanding of paintings. Under long presentation times (90 s)
      in Experiment 1, testing representative and abstract paintings, elaborative
      titles increased the understanding of abstract paintings but not their
      appreciation. In order to test predictions concerning the time course of
      understanding and aesthetic appreciation [Leder, H., Belke, B., Oeberst, A., &
      Augustin, D. (2004). A model of aesthetic appreciation and aesthetic judgments.
      British Journal of Psychology, 95(4), 489-508] in Experiment 2, abstract
      paintings were presented under two presentation times. For short presentation
      times (1 s), descriptive titles increased the understanding more than elaborative
      titles, whereas for medium presentation times (10 s), elaborative titles
      increased the understanding more than descriptive titles. Thus, with artworks a
      presentation time of around 10 s might be needed, to assign a meaning beyond the
      mere description. Only at medium presentation times did the participants with
      more art knowledge have a better understanding of the paintings than participants
      with less art knowledge. Thus, it seems that art knowledge becomes significant,
      if there is sufficient time to assign a meaning and the present studies reveal
      the importance of considering the time course in aesthetic appreciation.

PMID- 16289076
TI  - Subdividing the embryo: a role for Notch signaling during germ layer patterning
      in Xenopus laevis.
AB  - The development of all vertebrate embryos requires the establishment of a three
      dimensional coordinate system in order to pattern embryonic structures and create
      the complex shape of the adult organism. During the process of gastrulation, the
      three primary germ layers are created under the guidance of numerous signaling
      pathways, allowing cells to communicate during development. Cell-cell
      communication, mediated by receptors of the Notch family, has been shown to be
      involved in mediating diverse cellular behaviors during development and has been
      implicated in the regulation of cell fate decisions in both vertebrate and
      invertebrate organisms. In order to investigate a role for Notch signaling during
      boundary formation between the mesoderm and endoderm during gastrulation, we
      manipulated Notch signaling in gastrula stage embryos and examined gene
      expression in resultant tissues and organs. Our findings demonstrate a much
      broader role for Notch signaling during germ layer determination than previously
      reported in a vertebrate organism. Activation of the Notch pathway, specifically
      in gastrula stage embryos, results in a dramatic decrease in the expression of
      genes necessary to create many different types of mesodermal tissues while
      causing a dramatic expansion of endodermal tissue markers. Conversely, temporally
      controlled suppression of this pathway results in a loss of endodermal cell types
      and an expansion of molecular markers of mesoderm. Thus, our data are consistent
      with and significantly extend the implications of prior observations suggesting
      roles for Notch signaling during germ layer formation and establish an
      evolutionarily conserved role for Notch signaling in mediating mesoderm-endoderm
      boundaries during early vertebrate development.

PMID- 16289078
TI  - Free moment as a predictor of tibial stress fracture in distance runners.
AB  - Stress fractures are a common and serious overuse injury in runners, particularly
      female runners. They may be related to loading characteristics of the lower
      extremity during running stance. Some tibial stress fractures (TSFs) are spiral
      in nature and, therefore, may be related to torque. Free moment (FM) is a measure
      of torque about a vertical axis at the interface with the shoe and ground.
      Increases in FM variables may be related to a history of TSF in runners. The
      purpose of this cross-sectional study was to investigate differences in FM
      between female distance runners with and without a history of TSF and,
      additionally, to investigate the relationship between absolute FM and the
      occurrence of TSF. A group of 25 currently uninjured female distance runners with
      a history of TSF (28+/-10 years, 46+/-15 km week(-1)) and an age- and mileage
      matched control group of 25 healthy runners with no previous lower extremity
      fractures (26+/-9 years, 46+/-19 km week(-1)) participated in this study. Ground
      reaction forces and foot placement on the force platform were recorded during
      running at 3.7 ms(-1) (+/-5%). Peak adduction, braking peak and absolute peak FM
      and impulse were compared between groups using one-tailed t-tests. The predictive
      value of absolute peak FM was investigated via a binary logistic regression. All
      variables, except impulse, were significantly greater in runners with a history
      of TSF. Absolute peak FM had a significant predictive relationship with history
      of TSF. There is a significant relationship between higher values for FM
      variables and a history of TSF.

PMID- 16289077
TI  - Compressive nanomechanics of opposing aggrecan macromolecules.
AB  - In this study, we have measured the nanoscale compressive interactions between
      opposing aggrecan macromolecules in near-physiological conditions, in order to
      elucidate the molecular origins of tissue-level cartilage biomechanical behavior.
      Aggrecan molecules from fetal bovine epiphyseal cartilage were chemically end
      grafted to planar substrates, standard nanosized atomic force microscopy (AFM)
      probe tips (R(tip) approximately 50 nm), and larger colloidal probe tips (R(tip)
      approximately 2.5 microm). To assess normal nanomechanical interaction forces
      between opposing aggrecan layers, substrates with microcontact printed aggrecan
      were imaged using contact mode AFM, and aggrecan layer height (and hence
      deformation) was measured as a function of solution ionic strength (IS) and
      applied normal load. Then, using high-resolution force spectroscopy, nanoscale
      compressive forces between opposing aggrecan on the tip and substrate were
      measured versus tip-substrate separation distance in 0.001-1M NaCl. Nanosized
      tips enabled measurement of the molecular stiffness of 2-4 aggrecan while
      colloidal tips probed the nanomechanical properties of larger assemblies
      (approximately 10(4) molecules). The compressive stiffness of aggrecan was much
      higher when using a densely packed colloidal tip than the stiffness measured for
      using the nanosized tip with a few aggrecan, demonstrating the importance of
      lateral interactions to the normal nanomechanical properties. The measured stress
      at 0.1M NaCl (near-physiological ionic strength) increased sharply at aggrecan
      densities under the tip of approximately 40 mg/ml (physiological densities are
      approximately 20-80 mg/ml), corresponding to an average inter-GAG spacing of 4-5
      Debye lengths (4-5 nm); this characteristic spacing is consistent with the onset
      of significant electrostatic interactions between GAG chains of opposing aggrecan
      molecules. Comparison of nanomechanical data to the predictions of Poisson
      Boltzmann-based models further elucidated the regimes over which electrostatic
      and nonelectrostatic interactions affect aggrecan stiffness in compression. The
      most important aspects of this study include: the incorporation of experiments at
      two different length scales, the use of microcontact printing to enable
      quantification of aggrecan deformation and the corresponding nanoscale
      compressive stress vs. strain curve, the use of tips of differing functionality
      to provide insights into the molecular mechanisms of deformation, and the
      comparison of experimental data to the predictions of three increasingly refined
      Poisson-Boltzmann (P-B)-based theoretical models for the electrostatic double
      layer component of the interaction.

PMID- 16289079
TI  - Expanding the range of free calcium regulation in biological solutions.
AB  - Many biological systems use ethylene glycol bis (beta-aminoethylether)-N,N,N',N'
      tetraacetic acid (EGTA) to regulate the free calcium concentration
      ([Ca(2+)](free)) in the presence of physiological levels of free Mg(2+)
      ([Mg(2+)](free)). Frequently, it is necessary to work at [Ca(2+)](free) beyond
      EGTA's buffering capabilities. Therefore, we have developed methods to extend the
      buffering range by adding nitrilotriacetic acid (NTA) to solutions containing
      EGTA. This extension results from NTA having a lower K'(dCa) than EGTA. Such
      equilibria are solved by pCa Calculator, a computer program designed to aid in
      the study of Ca(2+)-dependent physiological processes while accounting for the
      effects of pH, temperature, and ionic strength. With multiple chelators and pH
      buffers from which to choose, pCa Calculator calculates the total concentration
      of each species required to achieve specified free concentrations of Ca(2+), ATP,
      and Mg(2+). The program is intuitive, user-friendly, and flexible enough to fix
      or vary the [Mg-ATP(2-)] and ionic strength. Moreover, it can account for
      increases in experimental volume from calcium addition. A comparative analysis is
      reported for testing solutions in the presence and absence of NTA by measuring
      the calcium binding affinity of fluorescent cardiac troponin C. These findings
      demonstrate that EGTA, when used in conjunction with NTA, improves and expands
      the regulation of free calcium in solution.

PMID- 16289080
TI  - Double-layer fluorescent zymography for processing protease detection.
AB  - We have developed a novel double-layer zymographic method for the detection of
      specific processing proteases of a target proprotease using a specific
      fluorescent substrate. The target processing proteases were separated using
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the gel was
      subsequently incubated with the target proenzyme used as the substrate. A
      cellulose acetate membrane was immersed in 10% glycerol and then soaked in the
      fluorescent substrate solution. The slab gel of the processing protease was
      covered with the fluorescent substrate membrane, making a double layer. The
      double layer was incubated at 37 degrees C, and the released fluorescent band, in
      which the processing protease was located, was detected using UV light. The
      advantages of the double-layer fluorescent zymographic method are as follows: (i)
      the specific detection of target proprotease using a specific substrate, (ii) a
      relatively rapid and sensitive method, (iii) effective detection using small
      amounts of crude material, and (iv) wide applications that include the detection
      of processing proteases and activators for target proteases. Typical examples
      used for the detection of the processing proteases, such as plasminogen
      activator, chymotrypsinogen activator, procaspase-3 processing protease and
      caspase-3 activators, using this new method are described in this article.

PMID- 16289081
TI  - The distribution of elements in the native starch granule as studied by particle
      induced X-ray emission and complementary methods.

PMID- 16289083
TI  - Classification and comparison of capillary columns by determination of the
      solution enthalpy of polar and non polar probes.
AB  - The behaviour and separation characteristics of capillary columns containing
      different stationary phases (bonded methyl- and methylphenylsiloxanes and
      polyglycols, and carbon layer and porous polymer) were classified and compared by
      measuring the values of the solution enthalpy DeltaHs of n-alkanes and 1-alcohols
      at various temperatures. The difference in DeltaHs values between straight-chain
      1-alcohols and n-alkanes with the same number of carbon atom (DeltaDeltaHs) does
      not change with changing temperature when gas-liquid partition stationary phases
      are used, but depends on the column composition and polarity and therefore
      permits to evaluate the influence of polarity on the solute-solvent interaction.
      The trend of the DeltaDeltaHs values is correlated with that of the DeltaC
      parameter and with the McReynolds' polarity constants.

PMID- 16289082
TI  - A Bpag1 isoform involved in cytoskeletal organization surrounding the nucleus.
AB  - Bpag1/dystonin proteins are giant cytoskeletal interacting proteins postulated to
      cross-link cytoskeletal filaments and thereby maintain cellular integrity. Loss
      of function of non-epithelial Bpag1 isoforms results in neuromuscular dysfunction
      and early postnatal death in mice. Multiple Bpag1 transcripts have been
      described, including those encoding protein isoforms that vary at the N-terminal
      end. Here, we have analyzed the subcellular localizations and cytoskeletal
      interactions of two isoforms, termed Bpag1a1 and Bpag1a2. We demonstrate that
      novel sequence at the 5' end of the Bpag1a2 transcript codes for an N-terminal
      transmembrane domain and targets the protein to the perinuclear region of the
      cell. Furthermore, we show that the endogenous Bpag1a2 protein is also present in
      the perinuclear region in myoblast cells. Differences in Bpag1a1 and Bpag1a2 with
      respect to the extent of their interactions with microtubules and microfilaments
      are also described, with Bpag1a2 fusion protein serving largely to associate with
      microfilaments surrounding the nucleus and Golgi apparatus. The overall structure
      and subcellular localizations of Bpag1a2 indicate possible functions in nuclear
      envelope structuring, nuclear tethering, and organization of membranous
      structures surrounding the nucleus.

PMID- 16289084
TI  - Physically incorporated extraction phase of solid-phase microextraction by sol
      gel technology.
AB  - A sol-gel method for the preparation of solid-phase microextraction (SPME) fiber
      was described and evaluated. The extraction phase of poly(dimethysiloxane) (PDMS)
      containing 3% vinyl group was physically incorporated into the sol-gel network
      without chemical bonding. The extraction phase itself is then partly crosslinked
      at 320 degrees C, forming an independent polymer network and can withstand
      desorption temperature of 290 degrees C. The headspace extraction of BTX by the
      fiber SPME was evaluated and the detection limit of o-xylene was down to 0.26
      ng/l. Extraction and determination of organophosphorus pesticides (OPPs) in
      water, orange juice and red wine by the SPME-GC thermionic specified detector
      (TSD) was validated. Limits of detection of the method for OPPs were below 10
      ng/l except methidathion. Relative standard deviations (RSDs) were in the range
      of 1-20% for pesticides being tested.

PMID- 16289085
TI  - Response surface optimization for determination of pesticide multiresidues by
      matrix solid-phase dispersion and gas chromatography.
AB  - An optimized multiresidue analysis method based on matrix solid-phase dispersion
      (MSPD) and gas chromatography (GC) is proposed for the determination of
      organochlorines and pyrethroids in the tea samples. Response surface methodology
      (RSM) was used to optimize the extraction conditions of MSPD, such as the sorbent
      type, eluent composition, dichloromethane concentration and eluting volume.
      Desirability function approach was employed to optimize the pesticide recoveries
      and matrix cleanup. Compromising the recoveries and cleanup degree, MSPD was
      carried out with Florisil as the sorbent and n-hexane-dichloromethane (1:1, v/v)
      as the eluent. The pesticide recoveries in tea samples were better than 80%
      spiked in the concentration range of 0.01-0.05mg/kg and the relative standard
      deviations were lower than 7%. The quantification limits of the pesticides were
      in the range of 0.002-0.06mg/kg, which were lower than the maximum residue limits
      of the pesticides in tea samples established by the European Union.

PMID- 16289086
TI  - Determination of the herbicide metribuzin and its major conversion products in
      soil by micellar electrokinetic chromatography.
AB  - In this paper, a multiresidue method for the analysis in soils of metribuzin (M)
      and its major conversion products, deaminometribuzin (DA), diketometribuzin (DK)
      and deaminodiketometribuzin (DADK) is developed. Considering the neutral and
      charged nature of the molecules, micellar electrokinetic chromatography (MEKC) is
      a very efficient method for the separation of these compounds, providing high
      efficiency and short analysis times. Different electrophoretic parameters were
      studied to optimize the separation, such as the buffer pH and concentration,
      sodium dodecyl sulphate (SDS) concentration, injection conditions and applied
      voltage. Excellent separation of the studied compounds was achieved within about
      7 min. Soil samples were previously extracted using methanol in an ultrasonic
      bath and then a SPE procedure was applied to pre-concentrate the analytes by
      passage through a LiChrolut EN sorbent column. Detection limits at the low
      microgkg(-1) level were obtained. The proposed method has been satisfactorily
      applied in soil samples showing recoveries ranging from 86.7% to 104.2% and
      represents a valuable alternative to high-performance liquid chromatography
      (HPLC).

PMID- 16289087
TI  - Trypanosoma rangeli: characterization of a Mg-dependent ecto ATP
      diphosphohydrolase activity.
AB  - In this work we describe the ability of living Trypanosoma rangeli to hydrolyze
      extracellular ATP. In these intact parasites whose viability was assessed before
      and after the reactions by motility and by Trypan blue dye exclusion, there was a
      low level of ATP hydrolysis in the absence of any divalent metal (1.53+/-0.12
      nmol P(i)/h x 10(7) cells). The ATP hydrolysis was stimulated by MgCl(2) and the
      Mg-dependent ecto-ATPase activity was 5.24+/-0.64 nmol P(i)/h x 10(7) cells. The
      Mg-dependent ecto-ATPase activity was linear with cell density and with time for
      at least 60 min. This stimulatory effect on the ATP hydrolysis was also observed
      when MgCl(2) was replaced by MnCl(2), but not by CaCl(2), SrCl(2), and ZnCl(2).
      The apparent K(m) for Mg-ATP2- was 0.53+/-0.11 mM. The optimum pH for the T.
      rangeli Mg-dependent ecto-ATPase activity lies in the alkaline range. This ecto
      ATPase activity was insensitive to inhibitors of other ATPase and phosphatase
      activities, such as oligomycin, sodium azide, bafilomycin A1, ouabain,
      furosemide, vanadate, molybdate, sodium fluoride, tartrate, and levamizole. To
      confirm that this Mg-dependent ATPase was an ecto-ATPase, we used an impermeant
      inhibitor, DIDS (4, 4'-diisothiocyanostylbene 2'-2'-disulfonic acid) as well as
      suramin, an antagonist of P2 purinoreceptors and inhibitor of some ecto-ATPases.
      These two reagents inhibited the Mg(2+)-dependent ATPase activity in a dose
      dependent manner. This ecto-ATPase activity was stimulated by carbohydrates
      involved in the attachment/invasion of salivary glands of Rhodnius prolixus and
      by lipophorin, an insect lipoprotein circulating in the hemolymph.

PMID- 16289089
TI  - [Contribution of Arantius' ligament to the control of left and middle hepatic
      veins].
AB  - Control of the left hepatic vein or of the common trunk left hepatic vein-middle
      hepatic vein during a hepatic resection is presumed difficult. This control is
      facilitated by the knowledge of the Arantius' ligament anatomy. The combined
      manoeuvre which associates lowering the top of segment I and section-traction of
      the Arantius' ligament allows exposure of the inferior aspect of the left or
      middle hepatic veins and allows safe dissection of these veins.

PMID- 16289088
TI  - Leishmania (Viannia) panamensis: cloning of the histone H1 genes by
      representational difference analysis.
AB  - We report the use of representational difference analysis to identify genes that
      have up-regulated expression in the amastigote life-cycle stage of Leishmania
      (Viannia) panamensis. This simultaneous process of selection and amplification
      allowed the cloning of several specific DNA fragments. One of them shows a high
      percentage of similarity with histone H1 genes from other Trypanosomatids and, as
      expected, is up-regulated in the amastigote life-cycle stage. The gene is present
      in two copies that are expressed at different levels in promastigotes and also in
      amastigotes, which seems to be a consequence of their different 3' untranslated
      regions.

PMID- 16289090
TI  - [Early recovery after digestive surgery. A multidisciplinary approach].

PMID- 16289091
TI  - [Octylcyanoacrylate (Dermabond) for skin closure at the time of head and neck
      surgery: a longitudinal prospective study].
AB  - OBJECTIVES: A prospective non-randomised evaluation of the octyl-2-cyanoacrylate
      (Dermabond) for skin closure in head and neck surgery. MATERIALS AND METHODS: An
      inception cohort of 52 patients managed by six otorhinolaryngologists head and
      neck surgeons at a single institution (university teaching and tertiary referral
      center) during the months of May-July 2004. The length of the skin incision
      varied from 3 to 30 cm (mean: 7 cm). Morbidity evaluation, longitudinal analysis
      of the evolution of the scar, and analysis of the degree of satisfaction.
      RESULTS: Postoperative death was not encountered. The overall morbidity rate was
      3.8% (2/52). There was no instances of wound dehiscence's. A subcutaneous abscess
      was noted in one patient. From an aesthetic point of view, the scar appearance
      was considered to be slightly retracted during the first postoperative month and
      to be very good 2 to 4 months from initial surgery. Only one patient developed a
      minimal cheloid scar. Among the 47 patients who expressed an opinion
      postoperatively regarding the use of the octyl-2-cyanoacrylate (Dermabond) for
      skin closure, the degree of satisfaction was very high due to the ability to take
      an early shower (40 patients) followed by the lack of skin sutures (5 patients)
      and the lack of any allergic skin reaction (2 patients). CONCLUSION: At our
      department, the octyl-2-cyanoacrylate (Dermabond) for skin closure at the time of
      head and neck surgery is becoming more and more utilized due to the completion of
      a solid and aesthetic suture, the ability to take an early shower and the high
      degree of satisfaction expressed by the patients.

PMID- 16289092
TI  - [Lateral endoscopic approach for thyroid and parathyroid surgery].
AB  - The endoscopic lateral approach in thyroid and parathyroid surgery is achieved by
      developing the plane between the carotid sheath laterally and the strap muscles
      medially. This approach allows direct access to the posterior aspect of the
      thyroid lobe, without the need for the dissection of the strap muscles and
      without the need for medial retraction of the thyroid during the procedure. The
      lateral approach aided by endoscopic magnification provides the surgeon with the
      ideal view with which to safely dissect the vital structures found in the retro
      thyroid space such as the inferior thyroid artery, the recurrent laryngeal nerve
      and the parathyroid glands. This approach was initially adopted in primary
      hyperparathyroidism caused by a single adenoma that had been localized
      preoperatively. It is now also offered to patients with an isolated thyroid
      nodule smaller than 25 mm in diameter requiring surgical excision. Experience
      with 408 parathyroidectomies and the preliminary results of 38 thyroid
      lobectomies allows the authors to recommend this technique to appropriately
      selected patients.

PMID- 16289093
TI  - Establishment of a strategy for the rapid generation of a monoclonal antibody
      against the human protein SNEV (hNMP200) by flow-cytometric cell sorting.
AB  - The screening for antigen-specific hybridoma cells with adequate production rates
      is still a time-, labour- and money-consuming procedure. A reduction in cell
      culture testing by specifically selecting those fused cells that produce antibody
      could therefore make hybridoma technology more attractive, even for small
      research groups or for newly discovered proteins at an early stage of research.
      Additional problems, such as the requirement to produce sufficient amounts of the
      unknown protein at a purity that allows specific immunisation of mice and testing
      of the resulting hybridoma clones, also need to be overcome. Here we present a
      new strategy to isolate rapidly and efficiently monoclonal antibodies against new
      proteins, for which only sequence information at the DNA level is known. The
      strategy consists of fusion of the protein to a hexa-His-tag to allow easy
      purification, production in yeast and insect cells to reduce background
      immunisation with host cell proteins and the selection of IgG-producing hybridoma
      cells by flow-cytometric cell sorting using the affinity matrix secretion assay
      technique.

PMID- 16289094
TI  - Rapid rates of newly synthesized mitochondrial protein degradation are
      significantly affected by the generation of mitochondrial free radicals.
AB  - Exposure of biological material to high levels of free radicals causes extensive
      cellular damage. Reactive oxygen species (ROS) generated by mitochondria have
      been associated with a variety of diseases and aging. We investigated the effect
      of low-level mitochondrial ROS production on newly synthesized mitochondrial
      proteins which are potentially vulnerable to mitochondrial ROS due to their
      location and unfolded state. We show that elevated mitochondrial ROS increases
      the degradation of newly synthesized mitochondrial proteins with some proteins
      more sensitive than others. In the long term reduced assembly of mitochondrial
      complexes would affect mitochondrial function and may trigger a vicious cycle of
      mitochondrial ROS production.

PMID- 16289095
TI  - Sulfite facilitates LDL lipid oxidation by transition metal ions: a pro-oxidant
      in wine?
AB  - Lipid oxidation in LDL may play a role in atherogenesis. It has been shown that
      sulfite - a compound in the aqueous fraction of wine - could inhibit free radical
      (AAPH) mediated oxidation of plasma. Thus, sulfite has been proposed as an
      antioxidant. In contrast, the aqueous phase of wine has recently been shown to
      contain not fully identified compounds promoting transition metal ion (Cu(2+))
      initiated LDL oxidation. As transition metal ions can catalyse the auto-oxidation
      of sulfite, we studied the influence of sulfite on Cu(2+) initiated LDL
      oxidation. The results show that sulfite at concentrations found in vivo strongly
      facilitated LDL oxidation by Cu(2+). The LDL-oxidase activity of ceruloplasmin
      was also stimulated by sulfite. ROS formation by Cu(2+)/SO(3)(2-) was not
      inhibited by SOD but by catalase. We propose that formation of Cu(+), sulfite
      radicals (SO(3)*(-)) and hydroxyl radicals (OH(*)) is a mechanism by which
      sulfite could act as a pro-atherogenic agent in presence of transition metal
      ions.

PMID- 16289096
TI  - FADD deficiency sensitises Jurkat T cells to TNF-alpha-dependent necrosis during
      activation-induced cell death.
AB  - Activation-induced cell death (AICD) in activated T lymphocytes is largely
      mediated by Fas/Fas ligand (FasL) interaction. The cytoplasmic adaptor molecule
      Fas-associated death domain protein (FADD) plays an essential role in the
      apoptotic signalling of the Fas death pathway. In the present study, we observed
      that FADD deficient (FADD(-/-)) Jurkat T cells undergo AICD to a similar extent
      as wild-type cells. AICD in wild-type Jurkat T cells is via apoptosis, whereas it
      is non-apoptotic in FADD(-/-) cells. The latter took up propidium iodide, exhibit
      a loss in mitochondrial membrane potential and have no detectable cleavage
      products of caspase-8 or -3 activation, suggesting that these cells die by
      necrosis. Wild-type Jurkat T cells undergo apoptosis when incubated with
      recombinant FasL and Trail but not with TNF-alpha. In contrast, FADD(-/-) Jurkat
      T cells are resistant to FasL and Trail but die of necrosis when incubated with
      TNF-alpha. We showed that neutralising anti-TNF-alpha blocked AICD as well as TNF
      alpha-induced necrosis in FADD(-/-) Jurkat T cells. Furthermore, down regulating
      the receptor interacting protein, RIP, with geldanamycin treatment, which is
      essential for TNF-alpha signalling, markedly inhibited AICD in FADD(-/-) Jurkat T
      cells. In addition, caspase-8-deficient Jurkat T cells are resistant to Fas- and
      TNF-alpha-induced cell death. Taken together, our results suggest that a
      deficiency in FADD and not caspase-8 or the inhibition of the Fas signalling
      pathway sensitises Jurkat T cells to TNF-alpha-dependent necrosis during AICD.

PMID- 16289097
TI  - RFX-1, a putative alpha Adducin interacting protein in a human kidney library.
AB  - Adducin regulates tubular absorption of sodium by modulating the expression
      levels of the sodium-potassium-ATPase in renal tubular cells. Adducin is a
      candidate gene in the pathogenesis of hypertension. Yeast two hybrid screen
      showed a specific interaction between human alpha Adducin and the regulatory
      factor for X box (RFX-1), a nuclear protein that down regulates the expression of
      several proteins in non neuronal cells. The interaction was confirmed in cells
      through co-immunoprecipitation and colocalization experiments. The binding of
      alpha Adducin to RFX-I and their nuclear co-localization suggests that Adducin
      can have a role in modulating the transcriptional regulating activity of RFX-I.

PMID- 16289098
TI  - Reconstitution of an apicoplast-localised electron transfer pathway involved in
      the isoprenoid biosynthesis of Plasmodium falciparum.
AB  - In the malaria parasite Plasmodium falciparum isoprenoid precursors are
      synthesised inside a plastid-like organelle (apicoplast) by the mevalonate
      independent 1-deoxy-d-xylulose-5-phosphate (DOXP) pathway. The last reaction step
      of the DOXP pathway is catalysed by the LytB enzyme which contains a [4Fe-4S]
      cluster. In this study, LytB of P. falciparum was shown to be catalytically
      active in the presence of an NADPH dependent electron transfer system comprising
      ferredoxin and ferredoxin-NADP(+) reductase. LytB and ferredoxin were found to
      form a stable protein complex. These data suggest that the ferredoxin/ferredoxin
      NADP(+) reductase redox system serves as the physiological electron donor for
      LytB in the apicoplast of P. falciparum.

PMID- 16289100
TI  - An inhibitor of c-Jun N-terminal kinases (CEP-11004) counteracts the anti-HIV-1
      action of trichosanthin.
AB  - Trichosanthin (TCS) is a type I ribosome-inactivating protein possessing multiple
      biological and pharmacological activities. One of its major actions is inhibition
      of human immunodeficiency virus (HIV) replication. The mechanism is still not
      clear. It is generally believed that this action is mediated via ribosome
      inactivation. Recently, we found that some TCS mutants with full ribosome
      inactivating activity were devoid of anti-HIV-1 effect. This suggested that there
      might be other mechanisms contributing to the anti-HIV-1 action. This study
      showed that a commonly used c-Jun N-terminal kinases inhibitor (CEP-11004) could
      counteract the antiviral action of TCS in C8166 cells. CEP-11004 alone had no
      effect on HIV-1 replication and TCS alone significantly inhibited this process.
      When CEP-11004 was used together with TCS, the antiviral action of TCS was much
      reduced. Two methods were used to assess viral replication. (1) By measuring the
      HIV-1 reverse transcriptase, TCS on the average reduced viral replication to 52+/
      4%. With CEP-11004 pretreatment, TCS appeared to lose the HIV-1 inhibitory
      activity with viral replication stood at 101+/-7%. (2) By measuring HIV-1 p24,
      TCS reduced viral replication to 68+/-4%. With CEP-11004 pretreatment, TCS again
      seemed to lose its anti-HIV-1 activity with HIV-1 replication rose back to 101+/
      4%. Both indexes indicated that CEP-11004 counteracted the antiviral action of
      TCS. Phosphorylation of JNK on the other hand was only slightly elevated by 1.5
      fold by TCS and CEP-11004 inhibited this elevation. These results suggested that
      the anti-HIV-1 effect of TCS may be related to the MAPK signal process downstream
      from the point of CEP inhibition.

PMID- 16289099
TI  - Over-production of IFN-gamma and IL-12 in AhR-null mice.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that mediates toxicity of environmental pollutants such as 2,3,7,8
      tetrachlorodibenzo-p-dioxin. The exposure to AhR agonists results in profound
      suppression of cellular and humoral immune responses and compromises host to
      infectious disease. Therefore, to define the role of AhR in the immune response,
      spleen cells from ovalbumin (OVA)-immunized and naive mice were removed and
      stimulated in vitro with either OVA or mitogen concanavalin-A (Con A),
      respectively. Proliferation, CD19+, F4/80+, CD4+ and CD8+ T cells expansion and
      cytokines production were measured in C57BL/6-AhR-/- mice (AhR-/-) and compared
      with immune response in similarly immunized age-matched wild type (AhR+/+) mice.
      In response to OVA immunization, AhR-/- mice had similar levels of serum OVA
      specific IgG2a, IgG1, and IgG2b compared with AhR+/+ animals. However, AhR-/-
      mice showed splenomegalia and an increase in B cells. No changes were observed on
      proliferation and IL-4 secretion, although AhR-/- cells produced more IFN-gamma
      and IL-12 than AhR+/+ cells. Similar results were observed with Con A
      stimulation, a decrease on IL-5 and no change on IL-2 secretion were observed on
      AhR-/- cells compared with AhR+/+ cells in response to Con A stimulation. High
      levels of IFN-gamma mRNA were detected in AhR-/- lymphocytes, but IL-4 mRNA
      levels in AhR-/- cells were similar to those in AhR+/+ mice. These data suggest
      that AhR may play an important role in the normal development and function of
      immune system by down-regulating IFN-gamma and IL-12 expression.

PMID- 16289101
TI  - Solution structure of alpha-conotoxin PIA, a novel antagonist of alpha6 subunit
      containing nicotinic acetylcholine receptors.
AB  - alpha-Conotoxin PIA is a novel nicotinic acetylcholine receptor (nAChR)
      antagonist isolated from Conus purpurascens that targets nAChR subtypes
      containing alpha6 and alpha3 subunits. alpha-conotoxin PIA displays 75-fold
      higher affinity for rat alpha6/alpha3beta2beta3 nAChRs than for rat alpha3beta2
      nAChRs. We have determined the three-dimensional structure of alpha-conotoxin PIA
      by nuclear magnetic resonance spectroscopy. The alpha-conotoxin PIA has an "omega
      shaped" overall topology as other alpha4/7 subfamily conotoxins. Yet, unlike
      other neuronally targeted alpha4/7-conotoxins, its N-terminal tail Arg1-Asp2-Pro3
      protrudes out of its main molecular body because Asp2-Pro3-Cys4-Cys5 forms a
      stable type I beta-turn. In addition, a kink introduced by Pro15 in the second
      loop of this toxin provides a distinct steric and electrostatic environment from
      those in alpha-conotoxins MII and GIC. By comparing the structure of alpha
      conotoxin PIA with other functionally related alpha-conotoxins we suggest
      structural features in alpha-conotoxin PIA that may be associated with its unique
      receptor recognition profile.

PMID- 16289102
TI  - Retinoic acid via RARalpha inhibits the expression of 24-hydroxylase in human
      prostate stromal cells.
AB  - 25-Hydroxyvitamin D(3)-24-hydroxylase (24-hydroxylase) is an important
      inactivating enzyme and its expression is induced by 25-hydroxyvitamin D3
      (25OHD3) and 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3) through action of
      heterodimers of vitamin D receptor (VDR) and retinoid X receptor (RXR). RXRs also
      act as heterodimer partners for retinoic acid receptors (RARs), mediating the
      action of all-trans-retinoic acid (ATRA). Prostate stroma plays a crucial role in
      prostate cancer development and benign prostatic hyperplasia. We demonstrate here
      that ATRA markedly reduced the expression of 24-hydroxylase mRNA induced by
      25OHD3 and 1alpha,25-(OH)2D3 in human prostatic stromal cells P29SN and P32S but
      not in epithelial cells PrEC or cancer cells LNCaP. By using transfection and RAR
      selective ligands, we found that the inhibitory effect of ATRA on 24-hydroxylase
      expression in stromal cells was mediated by RARalpha but not by RARbeta.
      Moreover, the ATRA-induced expression of RARbeta was also mediated by RARalpha.
      The combined treatment of 1alpha,25-(OH)2D3 and RARalpha agonist Am80 at 10 nM
      exhibited strong growth-inhibitory effect whereas either alone had no effect. Our
      data suggest that ATRA suppresses 24-hydroxylase expression through RARalpha
      dependent signaling pathway and can enhance vitamin D action in suppression of
      cell growth.

PMID- 16289103
TI  - A retrovirus restriction factor TRIM5alpha is transcriptionally regulated by
      interferons.
AB  - TRIM5alpha is a member of tripartite motif protein family and recently identified
      as a restriction factor for retroviral infection in a species-specific manner.
      Human TRIM5alpha gene is located on chromosomal position 11p15 in a cluster with
      other TRIM genes including TRIM6, 21, 22, and 34. We show here that interferon
      (IFN) upregulates TRIM5alpha mRNA expression in HeLa and HepG2 cells by
      performing Northern blot analysis and quantitative real-time PCR. TRIM5alpha
      promoter activity was IFN inducible as confirmed by luciferase assay using a
      reporter plasmid that contained the 5'-flanking region of TRIM5alpha. Mutational
      analysis has revealed that IFNs activate TRIM5alpha promoter activity through a
      putative interferon-stimulated response element (ISRE). Intriguingly, another IFN
      responsive protein signal transducer and activator of transcription factor 1
      (STAT1) binds to the ISRE sequence as shown by electrophoretic mobility shift
      assay using HeLa cell extracts. We have raised a specific polyclonal antibody
      against TRIM5alpha and confirmed that TRIM5alpha protein expression is inducible
      by IFN-beta in HeLa cells. These results lead us to define that the transcription
      and protein synthesis of TRIM5alpha could be modulated by IFN, suggesting that
      TRIM5alpha may play a role in an IFN-induced antiviral state against retrovirus
      infection.

PMID- 16289104
TI  - In vitro selection of DNA aptamers binding ethanolamine.
AB  - We have identified aptamers (synthetic oligonucleotides) binding to the very
      small molecule ethanolamine with high affinity down to the low nanomolar range.
      These aptamers were selected for their ability to bind to ethanolamine
      immobilised on magnetic beads, from an 96mer library of initially about 1 x
      10(16) randomised ssDNA molecules. The dissociation constants of these aptamers
      range between K(D)=6 and K(D)=19 nmol L(-1). The aim of the development of
      ethanolamine aptamers is their use for the detection of this substance in
      clinical and environmental analysis. Ethanolamine is associated with several
      diseases. Moreover, ethanolamine and its derivatives di- and tri-ethanolamine are
      used in chemical and cosmetic industries. The use of biosensors with ethanolamine
      aptamer as new molecular recognition element could be an innovative method for an
      easy and fast detection of ethanolamine.

PMID- 16289105
TI  - Saikosaponin-d inhibits T cell activation through the modulation of PKCtheta,
      JNK, and NF-kappaB transcription factor.
AB  - The effects of saikosaponin-d, a triterpene saponin derived from Bupleurum
      falcatum L. (Umbelliferae), on the signaling pathways of T cell activation were
      examined. The results showed that saikosaponin-d potently suppressed both early
      (CD69) and late (CD71) expressions of mouse T cells stimulated with Con A or PMA.
      It interfered with PKCtheta translocation from cytosol to membrane fraction and
      inhibited the phosphorylations of IkappaBalpha and JNK, but not ERK, in PMA
      activated mouse T cells. Additionally, it inhibited PMA and ionomycin-stimulated
      IL-2 production in mouse T cells. In summary, these results indicate that the
      mechanism by which saikosaponin-d inhibits T cell activation would involve the
      suppression of CD69 and CD71 expressions and IL-2 production, and the modulation
      of PKC pathway through PKCtheta, JNK, and NF-kappaB transcription factor. This
      may herald a novel approach for further studies of saikosaponin-d as a candidate
      for use in the treatment of inflammatory and autoimmune diseases.

PMID- 16289106
TI  - Characterization of a novel autophagy-specific gene, ATG29.
AB  - Autophagy is a process whereby cytoplasmic proteins and organelles are
      sequestered for bulk degradation in the vacuole/lysosome. At present, 16 ATG
      genes have been found that are essential for autophagosome formation in the yeast
      Saccharomyces cerevisiae. Most of these genes are also involved in the cytoplasm
      to vacuole transport pathway, which shares machinery with autophagy. Most Atg
      proteins are colocalized at the pre-autophagosomal structure (PAS), from which
      the autophagosome is thought to originate, but the precise mechanism of autophagy
      remains poorly understood. During a genetic screen aimed to obtain novel gene(s)
      required for autophagy, we identified a novel ORF, ATG29/YPL166w. atg29Delta
      cells were sensitive to starvation and induction of autophagy was severely
      retarded. However, the Cvt pathway operated normally. Therefore, ATG29 is an ATG
      gene specifically required for autophagy. Additionally, an Atg29-GFP fusion
      protein was observed to localize to the PAS. From these results, we propose that
      Atg29 functions in autophagosome formation at the PAS in collaboration with other
      Atg proteins.

PMID- 16289107
TI  - Hydralazine is a powerful inhibitor of peroxynitrite formation as a possible
      explanation for its beneficial effects on prognosis in patients with congestive
      heart failure.
AB  - The hemodynamic and anti-ischemic effects of nitroglycerin (GTN) are rapidly
      blunted as a result of the development of nitrate tolerance. Hydralazine has been
      shown to prevent tolerance in experimental and clinical studies, all of which may
      be at least in part secondary to antioxidant properties of this compound. The
      antioxidant effects of hydralazine were tested in cell free systems, cultured
      smooth muscle cells, isolated mitochondria, and isolated vessels. Inhibitory
      effects on the formation of superoxide and/or peroxynitrite formation were tested
      using lucigenin and L-012 enhanced chemiluminescence as well as DHE-fluorescence.
      The peroxynitrite scavenging properties were also assessed by inhibition of
      nitration of phenol. Prevention of impairment of NO downstream signaling and GTN
      bioactivation was determined by measurement of P-VASP (surrogate parameter for
      the activity of the cGMP-dependent kinase-I, cGK-I) and mitochondrial aldehyde
      dehydrogenase (ALDH-2) activity. Hydralazine dose-dependently decreased the
      chemiluminescence signal induced by peroxynitrite from SIN-1 and by superoxide
      from HX/XO in a cell free system, by superoxide in smooth muscle cells and
      mitochondria acutely challenged with GTN. Moreover, hydralazine inhibited the
      peroxynitrite-mediated nitration of phenols as well as proteins in smooth muscle
      cells in a dose-dependent fashion. Finally, hydralazine normalized impaired cGK-I
      activity as well as impaired vascular ALDH-2 activity. Our results indicate that
      hydralazine is a highly potent radical scavenger. Thus, the combination with
      isosorbide dinitrate (ISDN) will favorably influence the nitroso-redox balance in
      the cardiovascular system in patients with congestive heart failure and may
      explain at least in part the improvement of prognosis in patients with chronic
      congestive heart failure.

PMID- 16289108
TI  - GPR40 gene expression in human pancreas and insulinoma.
AB  - To assess gene expression of a membrane-bound G-protein-coupled fatty acid
      receptor, GPR40, in the human pancreas and islet cell tumors obtained at surgery
      were analyzed. The mRNA level of the GPR40 gene in isolated pancreatic islets was
      approximately 20-fold higher than that in the pancreas, and the level was
      comparable to or rather higher than that of the sulfonylurea receptor 1 gene,
      which is known to be expressed abundantly in human pancreatic beta cells. A large
      amount of GPR40 mRNA was detected in tissue extracts from two cases of
      insulinoma, whereas the expression was undetectable in glucagonoma or gastrinoma.
      The present study demonstrates that GPR40 mRNA is expressed predominantly in
      pancreatic islets in humans and that GPR40 mRNA is expressed solely in human
      insulinoma among islet cell tumors. These results indicate that GPR40 is probably
      expressed in pancreatic beta cells in the human pancreas.

PMID- 16289109
TI  - The interaction between ICOS and B7RP-1 is not required for the development of
      experimental murine allergic conjunctivitis.
AB  - It is still unclear whether the interaction between inducible costimulator (ICOS)
      and its ligand, B7 related protein (B7RP)-1, is important for the development of
      allergic diseases. We investigated whether blocking the ICOS/B7RP-1 interaction
      affects the development of murine experimental allergic conjunctivitis (EC). EC
      was induced in Balb/c mice either by active immunization of ragweed (RW) or by
      transferring RW-primed splenocytes, followed by challenge with RW-containing eye
      drops. The mice were treated with anti-B7RP-1 antibody (Ab) or normal rat
      immunoglobulin G (IgG) during either the induction or effector phase. Regardless
      of the induction method or when the animals were treated, eosinophil infiltration
      into the conjunctiva was not affected by the anti-B7RP-1 Ab treatment. Splenocyte
      responses were not largely affected by this treatment. However, serum Ig levels
      were significantly reduced. These data suggest that blocking the ICOS/B7RP-1 in
      allergic diseases may not always be therapeutic.

PMID- 16289110
TI  - Negatively charged phospholipids suppress IFN-gamma production in T cells.
AB  - The effect of phospholipids on IFN-gamma production in mouse T cells was
      investigated. Phosphatidylserine (PS), which has a negatively charged head group,
      completely inhibited IFN-gamma production in splenic naive T cells and antigen
      dependent IFN-gamma production in Th1 clone 42-6A cells, whereas other
      phospholipids, which have neutrally charged head group, had no effect. The
      structural requirements for IFN-gamma inhibitory effects by PS were investigated,
      and dimyristoyl-PS (C14: 0) and dipalmitoyl-PS (C16: 0) had no effect on IFN
      gamma production, and interestingly, distearoyl-PS (18: 0) increased IFN-gamma
      production. Dioleoyl-PS (C18: 1), dilinoleoyl-PS (C18: 2), and oleoyl-lyso-PS
      (C18: 1) completely inhibited IFN-gamma production. To clarify this mechanism, we
      focused on the stability of IFN-gamma mRNA, and the treatment of splenic naive T
      cells with PS brought about 40% reductions in IFN-gamma mRNA expression in the
      presence of actinomycin D. Collectively, IFN-gamma inhibitory effects by PS are
      highly dependent on the molecular structure of PS and involve the decreasing of
      the stability of IFN-gamma mRNA.

PMID- 16289111
TI  - Identification and phylogenetic analysis of Arsenophonus- and Photorhabdus-type
      bacteria from adult Hippoboscidae and Streblidae (Hippoboscoidea).
AB  - This is the first report of Arsenophonus- and Photorhabdus-type bacteria from
      Streblidae (bat flies) and Hippoboscidae (louse flies, keds). Strains were
      detected by means of polymerase chain reaction of 16S rDNA, and phylogenetic
      analysis determined the relationship of the obtained sequences to previously
      reported sequences in GenBank. Phylogenetic analysis by means of maximum
      parsimony revealed that all isolated Arsenophonus spp. 16S rDNA sequences formed
      a monophyletic sub-clade within other insect Arsenophonus spp., while the
      Photorhabdus spp. sequences are part of a monophyletic clade including
      Photorhabdus spp., Xenorhabdus spp. and Proteus spp.

PMID- 16289112
TI  - The role of progestin receptors and the mitogen-activated protein kinase pathway
      in delta opioid receptor facilitation of female reproductive behaviors.
AB  - The present study investigated the role of the progestin receptor (PR) and the
      mitogen-activated protein kinase (MAPK) pathway in the facilitation of lordosis
      behavior by the delta opioid receptor agonist [D-Pen(2), D-Pen(5)]-enkephalin
      (DPDPE). Ovariectomized, estrogen-primed rats were treated with the PR antagonist
      RU486 or the MAPK inhibitor PD98059 prior to intraventricular (icv) infusion of
      DPDPE. Both RU486 and PD98059 blocked receptive and proceptive behaviors induced
      by DPDPE at 60 min, and RU486 continued to inhibit estrous behavior at 90 min.
      Because delta opioid receptors can activate the p42/44 MAPKs, extracellular
      signal regulated kinases (ERK), we determined the effects of DPDPE on ERK
      phosphorylation. Icv infusion of DPDPE increased the levels of phosphorylated ERK
      in the hypothalamus and preoptic area of female rats, assessed by immunoblotting.
      These results support the participation of the PR and the MAPK pathway in the
      facilitation of lordosis behavior by delta opioid receptors.

PMID- 16289113
TI  - Stalled folding mutants in the triple beta-helix domain of the phage P22
      tailspike adhesin.
AB  - The trimeric bacteriophage P22 tailspike adhesin exhibits a domain in which three
      extended strands intertwine, forming a single turn of a triple beta-helix. This
      domain contains a single hydrophobic core composed of residues contributed by
      each of the three sister polypeptide chains. The triple beta-helix functions as a
      molecular clamp, increasing the stability of this elongated structural protein.
      During folding of the tailspike protein, the last precursor before the native
      state is a partially folded trimeric intermediate called the protrimer. The
      transition from the protrimer to the native state results in a structure that is
      resistant to denaturation by heat, chemical denaturants, and proteases. Random
      mutations were made in the region encoding residues 540-548, where the sister
      chains begin to wrap around each other. From a set of 26 unique single amino acid
      substitutions, we characterized mutations at G546, N547, and I548 that retarded
      or blocked the protrimer to native trimer transition. In contrast, many non
      conservative substitutions were tolerated at residues 540-544. Sucrose gradient
      analysis showed that protrimer-like mutants had reduced sedimentation, 8.0 S to
      8.3 S versus 9.3 S for the native trimer. Mutants affected in the protrimer to
      native trimer transition were also destabilized in their native state. These data
      suggest that the folding of the triple beta-helix domain drives transition of the
      protrimer to the native state and is accompanied by a major rearrangement of
      polypeptide chains.

PMID- 16289114
TI  - Structural consequences of the pH-induced conformational switch in A.polyphemus
      pheromone-binding protein: mechanisms of ligand release.
AB  - Olfaction in moths is one of the most impressive examples of chemical
      communication found in nature for its exquisite sensitivity and selectivity.
      Pheromone-binding proteins (PBPs), present in the antennae of male moth and other
      insect species, bind the hydrophobic pheromone molecules and transport them to
      the G protein-coupled olfactory receptor proteins. The targeted delivery of these
      non-polar ligands to membrane-bound receptors involves ligand release on or near
      the target cell membranes, the molecular details of which are still not well
      understood. The PBP from the giant silk moth Antheraea polyphemus (ApolPBP) binds
      acetate pheromone only at pH above 6.0, and its structure at pH 6.3 has been
      determined previously. Here we report the solution NMR structure of ApolPBP at
      the acidic pH 5.2. Comparison of the present structure to that at neutral pH
      reveals the details of the pH-induced conformational changes and provides
      mechanistic clues for ligand release at acidic pH. The ApolPBP pH-induced
      structural change is quite different from that observed for alcohol binding
      Bombyx mori PBP (BmorPBP), where the C-terminal segment folds into a helix and
      occupies the ligand binding cavity. We observe a reorientation of helices alpha1,
      alpha3, and alpha4 at acidic pH caused by protonation of His69, His70 and His95
      in the interior. This provides the driving force behind the opening of the ligand
      binding cavity and the release of the pheromone molecule from its carrier protein
      near the membrane.

PMID- 16289115
TI  - The highly structured encapsidation signal of MuLV RNA is involved in the nuclear
      export of its unspliced RNA.
AB  - The encapsidation signal (Psi) of retroviruses is located in the 5' UTR of the
      viral genomic unspliced transcript and is highly structured. In the Psi of murine
      leukaemia virus (MuLV), four stem-loops, called A, B, C and D, promote
      dimerization and encapsidation of the MuLV unspliced RNA into virions. Through
      analysis of Psi-deleted transcripts, we found that the AB and CD motifs
      independently enhanced the cytoplasmic accumulation of RNAs. Furthermore, we
      showed that over-expression of the Psi sequence in the infected cells led to a
      competition with the nuclear export of unspliced MuLV transcripts, revealing a
      new function for these stem-loops in the transport of viral intron-containing
      RNAs from the nucleus to the cytoplasm.

PMID- 16289116
TI  - The ubiquitin-domain protein HERP forms a complex with components of the
      endoplasmic reticulum associated degradation pathway.
AB  - To eliminate misfolded proteins that accumulate in the endoplasmic reticulum (ER)
      the cell mainly relies on ubiquitin-proteasome dependent ER-associated protein
      degradation (ERAD). Proteolysis of ERAD substrates by the proteasome requires
      their ubiquitylation and retro-translocation from the ER to the cytoplasm. Here
      we describe a high molecular mass protein complex associated with the ER
      membrane, which facilitates ERAD. It contains the ubiquitin domain protein (UDP)
      HERP, the ubiquitin protein ligase HRD1, as well as the retro-translocation
      factors p97, Derlin-1 and VIMP. Our data on the structural arrangement of these
      ERAD proteins suggest that p97 interacts directly with membrane-resident
      components of the complex including Derlin-1 and HRD1, while HERP binds directly
      to HRD1. We propose that ubiquitylation, as well as retro-translocation of
      proteins from the ER are performed by this modular protein complex, which permits
      the close coordination of these consecutive steps within ERAD.

PMID- 16289117
TI  - Structural basis for the interaction of TAK1 kinase with its activating protein
      TAB1.
AB  - Transforming growth factor-beta (TGF-beta)-activated kinase 1 (TAK1) is a member
      of the MAPKKK family of protein kinases, and is involved in intracellular
      signalling pathways stimulated by transforming growth factor beta, interleukin-1
      and tumour necrosis factor-alpha. TAK1 is known to rely upon an additional
      protein, TAK1-binding protein 1 (TAB1), for complete activation. However, the
      molecular basis for this activation has yet to be elucidated. We have solved the
      crystal structure of a novel TAK1 chimeric protein and these data give insight
      into how TAK1 is activated by TAB1. Our results reveal a novel binding pocket on
      the TAK1 kinase domain whose shape complements that of a unique alpha-helix in
      the TAK1 binding domain of TAB1, providing the basis for an intimate hydrophobic
      association between the protein activator and its target.

PMID- 16289118
TI  - Design of lambda Cro fold: solution structure of a monomeric variant of the de
      novo protein.
AB  - One of the classical DNA-binding proteins, bacteriophage lambda Cro, forms a
      homodimer with a unique fold of alpha-helices and beta-sheets. We have
      computationally designed an artificial sequence of 60 amino acid residues to
      stabilize the backbone tertiary structure of the lambda Cro dimer by simulated
      annealing using knowledge-based structure-sequence compatibility functions. The
      designed amino acid sequence has 25% identity with that of natural lambda Cro and
      preserves Phe58, which is important for formation of the stably folded structure
      of lambda Cro. The designed dimer protein and its monomeric variant, which was
      redesigned by the insertion of a beta-hairpin sequence at the C-terminal region
      to prevent dimerization, were synthesized and biochemically characterized to be
      well folded. The designed protein was monomeric under a wide range of protein
      concentrations and its solution structure was determined by NMR spectroscopy. The
      solved structure is similar to that of a monomeric variant of natural lambda Cro
      with a root-mean-square deviation of the polypeptide backbones at 2.1A and has a
      well-packed protein core. Thus, our knowledge-based functions provide approximate
      but essential relationships between amino acid sequences and protein structures,
      and are useful for finding novel sequences that are foldable into a given target
      structure.

PMID- 16289119
TI  - Effect of acute hypoxic preconditioning on qEEG and functional recovery after
      cardiac arrest in rats.
AB  - Acute hypoxic preconditioning (AHPC) can confer neuroprotection from global
      cerebral ischemia such as cardiac arrest. We hypothesize that acute
      neuroprotection by AHPC will be detected early by quantitative EEG (qEEG) entropy
      analysis after asphyxial cardiac arrest (aCA). Cerebral ischemia lowers EEG
      signal randomness leading to low entropy. A qEEG entropy index defined as the
      duration when the entropy measure is 15% below uninjured baseline entropy is used
      as a measure of injury. We compared 3 groups of adult Wistar rats: (1) untreated
      controls that were subjected to 5 min of aCA and were resuscitated (n = 5); (2)
      AHPC-treated group with 10% FI O2 for 30 min, then 25 min of room air, 5 min of
      aCA followed by resuscitation (n = 5); and (3) a surgical sham group (no aCA) (n
      = 3). Functional outcome was assessed by neurodeficit score (NDS) which consisted
      of level of consciousness, cranial nerve, motor-sensory function, and simple
      behavioral tests (best = 100 and brain dead = 0). We found that increasing
      entropy index of injury at 0-5 h from return of spontaneous circulation (ROSC) is
      associated with worsening NDS at 24 h (linear regression: r = 0.81, P < 0.001).
      The NDS of the group sham (84.7 +/- 2.8) (mean +/- SEM) and AHPC group (84.6 +/-
      2.9, P > 0.05) was better than control injury group (52.2 +/- 8.4, P < 0.05)
      (ANOVA with Tukey test). We therefore conclude that AHPC confers acute
      neuroprotection at 24 h, which was detected by qEEG entropy during the first 5 h
      after injury.

PMID- 16289120
TI  - Influence of stationary phase solvation on shape selectivity and retention in
      reversed-phase liquid chromatography.
AB  - In the past few decades, shape selectivity has drawn a great deal of attention
      from chromatographers. The chemistry and characteristics of bonded stationary
      phases such as phase type, length of bonded phase, surface coverage, and silica
      surface material have an effect on the shape selectivity of the columns. Although
      the effects of bonded phase shape selectivity are relatively well understood, one
      remaining question is the effect of intercalated solvent on shape selectivity.
      The intercalation of organic modifier and water molecules into the stationary
      phase is believed to introduce more rigidity into bonded alkyl chains in RPLC.
      The use of gas chromatography (GC) opens a new dimension to approach this
      question. C18 columns 4 cm in length were prepared in our laboratory and used in
      both LC and GC experiments. Shape selectivity and thermodynamic constants for the
      transfer of a solute from the mobile phase to the stationary phase have been
      determined as a function of monomeric octadecyl stationary phase bonding
      densities over the range of 1.44-3.43 micromol/m2 and a polymeric phase (nominal
      surface coverage 4.77 micromol/m2). Comparing LC and GC experiments, we observed:
      (a) similar relationships between shape and phenyl selectivities with
      monomerically bonded C18 phase densities; (b) different correlation of
      thermodynamic quantities (DeltaH degrees , DeltaS degrees , and DeltaG degrees )
      versus bonded phase densities. The effects of high temperature and residual
      silanol groups are sources of difficulty in elucidation of the intercalated
      mobile phase role in selectivity and retention for GC measurements.

PMID- 16289121
TI  - Temperature-programmed retention indices for gas chromatography-mass spectroscopy
      analysis of plant essential oils.
AB  - A total of 95 volatile compounds from the essential oil in buds of Syringa oblata
      Lindl (lilac) were identified by gas chromatography-mass spectrometry (GC-MS)
      combined with heuristic evolving latent projections (HELP) and moving subwindow
      searching (MSS). The identified compounds are mainly aliphatic, terpenes and
      aromatic compounds. Their temperature-programmed retention indices (PTRIs) on HP
      5MS and DB-35MS at three heating rates of 2, 4 and 6 degrees C/min from 80 to 290
      degrees C were obtained, which showed that aliphatic compounds give nearly
      constant PTRIs and PTRIs of terpenoids do not vary much at different heating
      rates. But PTRIs of aromatic compounds exhibit relatively large temperature
      dependence. PTRIs vary much more on DB-35MS than those on HP-5MS according to the
      compound types. In general, differences of PTRIs between the two columns increase
      from aliphatic compounds to terpenoids to polycyclic aromatic compounds. The
      PTRIs in different heating rates were used as cross-references in the
      identification of components in the essential oil. When they were used in
      analysis of essential oil from flowers of lilac, good results were obtained.
      These PTRIs would be a part of our PTRI database being constructed on components
      from plant essential oils. The results also showed that efficiency and
      reliability were improved greatly when chemometric method and PTRIs were used as
      assistants of GC-MS in identification of chemical components in plant essential
      oils.

PMID- 16289122
TI  - Optimization of a hybrid chromatography-crystallization process for the
      separation of Troger's base enantiomers.
AB  - This paper presents an analysis of a hybrid process consisting of simulated
      moving bed (SMB) chromatography and crystallization and studies its performance
      for the separation of the Troger's base enantiomers. The SMB is simulated using a
      detailed model including column efficiency, thus, implying a proper evaluation of
      the effect of column size on column efficiency and separation performance. The
      crystallization operations are accounted for through material balances, assuming
      equilibrium between enantiopure crystals and mother liquor. A genetic algorithm
      is used to optimize the combined process, using proper definitions of objective
      functions. Multi-objective optimization of this hybrid process for productivity
      and evaporation cost in terms of operating parameters, column length, and SMB
      feed concentration shows an optimum SMB purity value as a trade off between
      increased SMB performance and recycle of the mother liquor.

PMID- 16289123
TI  - Muscarinic modulations of neuronal anticholinesterase responses.
AB  - Anticholinesterases (antiChEs) are increasingly used for treating patients with
      neurodegenerative diseases, but the dependence of their effects on the integrity
      of cholinergic functions has not yet been analyzed at the molecular level. Here,
      we report that manipulation of muscarinic neurotransmission confers drastic
      changes on antiChE responses in the rat brain. In the brains of naive, un
      stressed rats, the irreversible organophosphate antiChE,
      diisopropylfluorophosphonate (DFP) induced post-treatment accumulation of
      catalytically active G1 monomers of acetylcholinesterase (AChE). Pre-treatment
      with the selective M1 muscarinic antagonist, pirenzepine, but not the general
      muscarinic antagonist, scopolamine, attenuated this G1 increase. DFP-enhanced
      AChE gene expression was accompanied by diverted splicing from the primary AChE-S
      mRNA variant, encoding G4 synaptic membrane AChE-S tetramers, to "readthrough"
      AChE-R mRNA, which encodes soluble G1 monomers. Both the mRNA increase and the
      shifted splicing were long lasting (>24 h) and common to the parietal cortex and
      hippocampal CA1 and CA3 neurons. Importantly, the splicing shift was maximal
      under DFP alone, as compared with sham-injected rats, and virtually preventable
      by pre-treatment with pirenzepine. In contrast, induction of AChE transcription
      was less dependent on muscarinic function, resulting in AChE-S but not AChE-R
      increases. Our findings demonstrate distinct regulation of the enhanced
      transcription and the alternative splicing reactions to antiChE treatment and
      shed new light on the differential responses to antiChEs of demented patients
      with increasingly impaired cholinergic neurotransmission.

PMID- 16289125
TI  - Modelling the many-wrongs principle: the navigational advantages of aggregation
      in nomadic foragers.
AB  - We develop a simple individual-based model to gain an understanding of the
      drivers of aggregation behaviour in nomadic foragers. The model incorporates two
      key elements influencing nomadic foragers in variable environments: uncertainty
      regarding the location of food sources and variability in the spatio-temporal
      distribution of ephemeral food sources. A genetic algorithm is used to evolve
      parameters describing an individual's movement and aggregation strategy. We apply
      the aggregation model to a case study of the Bornean bearded pig (Sus barbatus).
      Bearded pigs are ideal for considering the foraging advantages of aggregation,
      because they are highly mobile and exhibit a variety of aggregation strategies,
      ranging from solitary and sedentary to mass aggregation and wide ranging
      migration. Our model demonstrates the "many-wrongs principle", and shows that
      environmental variability, uncertainty in the location of food sources, and local
      population density drive aggregation behaviour.

PMID- 16289124
TI  - Lessons from functional analysis of AChE covalent and noncovalent inhibitors for
      design of AD therapeutic agents.
AB  - Determination of the 3D-structure of acetylcholinesterase (AChE) of Torpedo
      californica over a decade ago, and more recently that of human enzyme together
      with extensive targeted mutagenesis of the mammalian AChEs led to a fine mapping
      of the multiple functional domains within the active center of the enzyme. Many
      of the contributions of this active center architecture to accommodation of
      noncovalent ligands could be deduced from the X-ray structures of the
      corresponding HuAChE complexes. Yet, Michaelis complexes leading to transient
      covalent adducts are not amenable to structural analysis. Since the rates of
      formation of the covalent adducts depend predominantly on the stabilities of the
      corresponding Michaelis complexes, it is essential to characterize the specific
      interactions contributing to stabilization of these complexes. Functional
      analysis of interactions with HuAChE enzymes allows for such characterization for
      carbamates, like pyridostigmine or rivastigmine, much in the same way as that for
      the noncovalent therapeutic ligands nivalin or aricept. In fact, the observed
      differences between the affinities toward carbamates and the noncovalent ligands
      seem to result from specific structural characteristics of the inhibitors rather
      than from the decomposition path of the particular complex. Replacements at the
      cation binding site (Trp86), hydrogen bond network (Glu202, Tyr133, Glu450), and
      hydrophobic pocket result in similar effects for the covalent as well as for the
      noncovalent inhibitors. Also, while the effects of perturbing the aromatic
      trapping of the catalytic His447 for pyridostigmine and nivalin were analogous to
      those for the substrate, the corresponding effects for rivastigmine and aricept
      were quite different. Thus, elucidation of the functional architecture of the
      HuAChE active center is bound to be of considerable utility in the current effort
      to design novel covalent AChE inhibitors as therapeutics for Alzheimer's disease
      (AD).

PMID- 16289126
TI  - pH dependence of friction forces between silica surfaces in solutions.
AB  - The pH dependence of the friction between a silica particle and a silica wafer
      was investigated using lateral force microscopy. Measurements were done in the
      range of 3.6 < or = pH < or = 10.6 and the effect of high loading force was also
      examined. It is found that the friction is independent of the pH of solutions and
      increases linearly with the applied load, when the pH is between 3.6 and 8.6. On
      the other hand, once the pH is above 9.0, the friction becomes extremely small
      and the dependence on the applied load becomes nonlinear. It is postulated that
      this transition is due to the development of a gel layer composed of polymer-like
      segments of silicilic acid anchored on the surface; at the lower applied load,
      this layer acts as a boundary lubricant between the surfaces, but, at the higher
      applied load, the entanglements of these segments and more direct contact between
      two solid surfaces leads to the increase of the friction. The effects found here
      are expected to play an important role in elucidating the basic mechanism of the
      planarization process of silica wafers.

PMID- 16289127
TI  - Coupling between electroosmotically driven flow and bipolar faradaic
      depolarization processes in electron-conducting microchannels.
AB  - A quantitative theory is proposed for the analysis of steady electroosmotically
      driven flows within conducting cylindrical microchannels. Beyond a threshold
      value of the electric field applied in the electrolyte solution and parallel to
      the conducting surface, electrochemical oxidation and reduction reactions take
      place at the two extremities of the substrate. The spatial distribution of the
      corresponding local faradaic currents along the bipolar electrode is
      intrinsically coupled to that of the electric field in solution. The nonuniform
      distribution of the electric field alters the double layer composition, and in
      particular the zeta-potential value, along the conducting surface via the
      occurrence of concomitant electronic and ionic double layer charging processes.
      The combined spatial dependencies of the lateral electric field and
      electrokinetic potential considerably affects the distribution of the
      electroosmotic velocity field in the directions parallel and perpendicular to the
      surface depolarized by faradaic processes. In this paper, the coupling between
      bipolar electrodic behavior and electroosmosis is explicitly investigated for the
      case of irreversible--that is, kinetically controlled--electron transfer
      reactions. Typical simulation results are presented and illustrate the
      possibility of controlling and optimizing electroosmotic flows in conducting
      channels by electrochemical means.

PMID- 16289128
TI  - Preparation of siloxy focal dendron-protected TiO2 nanoparticles and their
      photocatalysis.
AB  - TiO2 nanoparticles were synthesized at approximately 0 degrees C by hydrolyzing
      [(CH3)2CHO]4Ti in 1-propanol solutions of poly(amido amine) dendrons with a
      siloxy focal point and long alkyl chain spacers. Transmission electron
      microscopic photographs showed that TiO2 nanoparticle was 1-5 nm in size and
      protected by dendrons, when prepared at a mixing ratio 1:10 of Ti ion and
      dendron. At higher contents of Ti ion, TiO2 nanoparticles aggregated up to a
      maximum size of 90 nm, depending on the dendron generation (first to third). It
      was confirmed from X-ray photoelectron spectroscopy that Si-O-Ti covalent bond
      was formed in dendron-protected TiO2 nanoparticles. The ability of dendron
      protected TiO2 nanoparticles as a photocatalyst for the photodegradation of 2,4
      dichlorophenoxyacetic acid was higher than that of nonprotected nanoparticle and
      superior at higher generation. It was suggested that the dendrons protecting TiO2
      nanoparticle have enough void volume to conserve guest molecules and behave
      effectively as a reservoir of guest molecules.

PMID- 16289129
TI  - Viscosity and yield stress reduction in non-colloidal concentrated suspensions by
      surface modification with polymers and surfactants and/or nanoparticle addition.
AB  - A custom-designed apparatus termed the yield stress adaptor (YSA) has been used
      to evaluate the effect of polymer-surfactant coatings, and the addition of
      nanoparticles of different size, shape and surface chemistry, on the rheological
      properties of large hydrophilic particulates, sand, with the aim of reducing
      interparticle friction forces. Experimental results show that the flow properties
      of sand slurries at high volume fractions of sand (>50%) can be significantly
      enhanced by adding nanoparticles, and by surface modification with
      polymer/surfactant mixtures. A lesser effect is observed for polymer-only and
      surfactant-only coated samples. X-ray photoelectron spectroscopy was used to
      determine the concentration of organic species at the surface. The effect of
      polymer/surfactant concentration, adsorption time, polymer molecular weight, as
      well as surfactant charge and chemical structure were also addressed.

PMID- 16289130
TI  - Interactions of anionic dyes with silica-aminopropyl 1. A quantitative
      multivariate analysis of equilibrium adsorption and adsorption Gibbs free
      energies.
AB  - In this work silica-aminopropyl (Sil-NH2) was synthesized and employed to
      evaluate the quantitative roles of temperature, pH, dye concentration, and Hg(II)
      or anionic surfactant SDB interferents in the adsorptions of blue and red remazol
      dyes in aqueous medium using four distinct 2(4) factorial designs. The results
      were analyzed statistically using multiple regressions, Student's t-test,
      analysis of variance, and F-test. Polynomial modelings were used to define the
      most important factors affecting dye adsorption. The results indicate that the
      principal effects of dye concentration and pH, as well as most of the
      interactions of all factors, are statistically very important in relation to the
      equilibrium adsorption quantities. However, the adsorption Gibbs free energies
      are influenced, in general, only by pH, dye concentration, and some binary
      interactions. Temperature changes do not affect the deltaG values significantly.

PMID- 16289131
TI  - Dynamics of shear-thinning suspensions of core-shell structured latex particles.
AB  - The rheological behavior and microstructure of shear-thinning suspensions of core
      shell structured carboxylated latex particles were examined. The steady shear
      viscosity of the suspension increased with increasing dissociation of the
      carboxyl groups or increasing particle concentration, however the critical shear
      stress sigma(c) and inter-particle distance xi of the microstructure did not
      change. With increasing particle diameter, sigma(c) increased and xi decreased.
      These results were consistent with a Brownian hard sphere model, in which
      competition exists between the bulk mass transfer due to the applied field and
      diffusion of the particles. We confirmed that sigma(c) depends on xi, as
      expressed by sigma(c) = 3kT/4pi xi3. This relationship is consistent with the
      dynamics of a Brownian hard sphere model with particle diameter xi. Thus the
      dynamics of shear-thinning suspensions of core-shell particles can be explained
      by a Brownian thermodynamic model.

PMID- 16289132
TI  - DYRK2 and GSK-3 phosphorylate and promote the timely degradation of OMA-1, a key
      regulator of the oocyte-to-embryo transition in C. elegans.
AB  - Oocyte maturation and fertilization initiates a dynamic and tightly regulated
      process in which a non-dividing oocyte is transformed into a rapidly dividing
      embryo. We have shown previously that two C. elegans CCCH zinc finger proteins,
      OMA-1 and OMA-2, have an essential and redundant function in oocyte maturation.
      Both OMA-1 and OMA-2 are expressed only in oocytes and 1-cell embryos, and need
      to be degraded rapidly after the first mitotic division for embryogenesis to
      proceed normally. We report here a distinct redundant function for OMA-1 and OMA
      2 in the 1-cell embryo. Depletion of both oma-1 and oma-2 in embryos leads to
      embryonic lethality. We also show that OMA-1 protein is directly phosphorylated
      at T239 by the DYRK kinase MBK-2, and that phosphorylation at T239 is required
      both for OMA-1 function in the 1-cell embryo and its degradation after the first
      mitosis. OMA-1 phosphorylated at T239 is only detected within a short
      developmental window of 1-cell embryos, beginning soon after the proposed
      activation of MBK-2. Phosphorylation at T239 facilitates subsequent
      phosphorylation of OMA-1 by another kinase, GSK-3, at T339 in vitro.
      Phosphorylation at both T239 and T339 are essential for correctly-timed OMA-1
      degradation in vivo. We propose that a series of precisely-timed phosphorylation
      events regulates both the activity and the timing of degradation for OMA
      proteins, thereby allowing restricted and distinct functions of OMA-1 and OMA-2
      in the maturing oocyte and 1-cell embryo, ensuring a normal oocyte-to-embryo
      transition in C. elegans.

PMID- 16289133
TI  - A bHLH transcription factor gene, Twist-like 1, is essential for the formation of
      mesodermal tissues of Ciona juveniles.
AB  - Ascidian larval mesenchyme cells, comprising about 900 cells, are derived from
      the A7.6, B8.5 and B7.7 blastomere pairs in the 110-cell embryo. Previous studies
      showed that the properties of mesenchyme cells are not uniform among the three
      lines in embryos of Ciona savignyi and Ciona intestinalis. After metamorphosis,
      the larval mesenchyme cells form the mesodermal tissues or organs of the adult
      body. In the present study, the developmental fates of A7.6-, B8.5- and B7.7-line
      mesenchyme cells were traced using DiI to determine the origins of juvenile
      mesodermal tissues of C. savignyi. It was demonstrated that each of the A7.6-,
      B8.5- and B7.7-line mesenchyme cells is distributed in different positions of the
      larval trunk, and then give rise to the different mesodermal tissues of
      juveniles. Twist-like 1 is a transcription factor gene essential for the
      specification of larval mesenchyme cells. Knockdown of this gene with specific
      morpholino antisense oligonucleotides affected not only the specification of
      larval mesenchyme cells, but also the formation of most of the mesodermal tissues
      of juveniles. The juvenile mesodermal tissues in the Twist-like 1-knockdown
      specimen were never compensated by the surrounding tissues. The present results
      therefore indicate that Twist-like 1 is required for the differentiation of most
      mesodermal precursors of adults.

PMID- 16289134
TI  - Molecular evidence for a critical period in mural trophoblast development in
      bovine blastocysts.
AB  - Embryonic and extra-embryonic lineages are separated at the blastocyst stage in
      the mouse at the onset of implantation but well ahead of implantation in most
      mammals. To provide information on the development of the trophoblast lineage in
      late-implanting bovine embryos, we combined the use of molecular markers defining
      embryonic and extra-embryonic lineages in the mouse with a transcriptomic
      approach dedicated to the early steps of the elongation process, a characteristic
      feature of blastocyst development in ruminants. In this study, we present
      molecular evidence for differences between the cow and the mouse in the
      programming of trophoblast differentiation. This different programming
      encompasses: (i) the expression of epiblast specifying genes (Oct-4, Nanog) in
      bovine trophoblast cells at the onset of elongation, (ii) the transcription of
      proliferation markers in early elongating blastocysts, (iii) the early detection
      of trophoblast-specific transcripts related to extra-embryonic tissue's
      differentiation (Hand1, Ets2, IFN-tau) and (iv) the identification of a new
      transcript (c12) which displays a reciprocal pattern to that of Oct-4 and Nanog
      genes in the embryonic cells and for which no equivalent has thus far been found
      in the mouse. Altogether, these results tended to show that early elongation is a
      critical transition in bovine trophoblast development.

PMID- 16289136
TI  - Left-right asymmetry and congenital cardiac defects: getting to the heart of the
      matter in vertebrate left-right axis determination.
AB  - Cellular and molecular left-right differences that are present in the mesodermal
      heart fields suggest that the heart is lateralized from its inception. Left-right
      asymmetry persists as the heart fields coalesce to form the primary heart tube,
      and overt, morphological asymmetry first becomes evident when the heart tube
      undergoes looping morphogenesis. Thereafter, chamber formation, differentiation
      of the inflow and outflow tracts, and position of the heart relative to the
      midline are additional features of heart development that exhibit left-right
      differences. Observations made in human clinical studies and in animal models of
      laterality disease suggest that all of these features of cardiac development are
      influenced by the embryonic left-right body axis. When errors in left-right axis
      determination happen, they almost always are associated with complex congenital
      heart malformations. The purpose of this review is to highlight what is presently
      known about cardiac development and upstream processes of left-right axis
      determination, and to consider how perturbation of the left-right body plan might
      ultimately result in particular types of congenital heart defects.

PMID- 16289135
TI  - Oocyte-specific expression of Gpr3 is required for the maintenance of meiotic
      arrest in mouse oocytes.
AB  - The maintenance of meiotic prophase arrest in mouse oocytes within fully grown
      follicles, prior to the surge of luteinizing hormone (LH) that triggers meiotic
      resumption, depends on a high level of cAMP within the oocyte. cAMP is produced
      within the oocyte, at least in large part, by the G(s)-linked G-protein-coupled
      receptor, GPR3. Gpr3 is localized in the mouse oocyte but is also present
      throughout the follicle. To investigate whether Gpr3 in the follicle cells
      contributes to the maintenance of meiotic arrest, RNA interference (RNAi) was
      used to reduce the amount of Gpr3 RNA within follicle-enclosed oocytes. Follicle
      enclosed oocytes injected with small interfering double-stranded RNA (siRNA)
      targeting Gpr3, but not control siRNAs, stimulated the resumption of meiosis in
      the majority of oocytes following a 3-day culture period. Reduction of RNA was
      specific for Gpr3 because an unrelated gene was not reduced by microinjection of
      siRNA. Meiotic resumption was stimulated in isolated oocytes injected with the
      same siRNA and cultured for 1 to 2 days, but at a much lower rate than in
      follicle-enclosed oocytes that could be cultured for longer. These results
      demonstrate that GPR3 specifically in the oocyte, rather than in the follicle
      cells, is responsible for maintenance of meiotic arrest in mouse oocytes.
      Furthermore, the method developed here for specifically reducing RNA in follicle
      enclosed oocytes, which can be cultured for a sufficient time to reduce the level
      of endogenous protein, should be generally useful for targeting a wide range of
      other proteins that may be involved in meiotic arrest, the resumption of meiosis,
      fertilization, or early embryonic development.

PMID- 16289137
TI  - Expression and hormonal regulation of calcyclin-binding protein (CacyBP) in the
      mouse uterus during early pregnancy.
AB  - Calcyclin-binding protein (Siah-1-Interacting Protein, CacyBP/SIP), is a calcium
      signaling protein involved in the degradation of beta-catenin, however, little is
      known about its role in reproductive biology. The present study was to character
      its temporospatial expression pattern and regulation in mouse uterus and to
      investigate whether it plays a role in the regulation of normal endometrial
      events. While prominently expressed in both luminal and glandular epithelia,
      CacyBP underwent dynamic changes during early pregnancy. CacyBP expression was
      observed weakly from days 1-4. An intense accumulation in luminal and glandular
      epithelia as well as decidua surrounding the embryo at later stages (days 5-7)
      was observed. Most notably, CacyBP accumulation in trophoblast was pronounced at
      day 7. Using ovariectomized and pseudopregnant mice, we found that progesterone
      (P(4)) and 17beta-estradiol (E(2)) led to increased expression of CacyBP gene and
      this could be abolished by Ru486 and tamoxifen, respectively. Antisense
      oligonucleotides (ODNs) against CacyBP significantly inhibited cultured
      endometrial stromal cells' (ESCs) apoptosis induced by UV irradiation. Injection
      of antisense ODNs into mouse uterine horn severely impaired the number of
      implanted blastocysts. Taken together, our results suggested that CacyBP
      expression was positively regulated by P(4) and E(2). CacyBP may be involved in
      the regulation of endometrial cell apoptosis during early pregnancy and play an
      important role in mouse endometrial events such as pregrancy establishment.

PMID- 16289138
TI  - Differential regulation of anti-inflammatory proteins in human rheumatoid
      synoviocyte MH7A cell by celecoxib and ibuprofen.
AB  - Non-steroidal anti-inflammatory drugs are known to be the most widely used drugs
      to exert their anti-inflammatory activities. It was examined protein expression
      profiles of human rheumatoid fibroblast-like synoviocyte MH7A cells treated with
      celecoxib, a selective cyclooxygenase-2 inhibitor, or ibuprofen, a non-selective
      cyclooxygenase inhibitor, using two-dimensional gel electrophoresis for
      comparison the mechanism of the drugs. Altered expression pattern in response to
      celecoxib is significantly different from that of ibuprofen treated cells. When
      MH7A cells were treated with celecoxib, 28 proteins were affected at their
      expression levels. Among them, heat shock proteins (Hsp60 and 70), glucose
      regulated proteins (Hsp75 and 78) were observed to be up-regulated by 1 to 30
      microM concentrations of celecoxib but those proteins were not affected in
      ibuprofen treated cells. On the other hand, the expression of 19 proteins was
      changed by ibuprofen and the expression of apolipoprotein E, RNA binding motif 4,
      CTP-phosphocholine cytidylyltransferase, and phospholipase A2 inhibitory protein
      was only altered by ibuprofen. The expressions of 15 proteins were affected by
      both celecoxib and ibuprofen. Our results showed that celecoxib and ibuprofen,
      though they are known to act as cyclooxygenase inhibitors, could exert a
      different mode of acting mechanisms in anti-inflammatory processes. The chemical
      proteomic approach will be useful for figuring out the mode of actions of drugs.

PMID- 16289139
TI  - Comparison of psychic emergence reactions after (+/-)-ketamine and (+)-ketamine
      in mice.
AB  - Ketamine is a racemic mixture containing equal parts of (+)-ketamine and (-)
      ketamine. The ketamine enantiomorphs are different in anesthesia and psychic
      emergence reactions after anesthesia. Therefore, (+)-ketamine was compared with
      racemic ketamine in a number of randomized studies in volunteers and patients.
      However, their relations remain controversial. In the present studies, the
      psychic emergence reactions after injection of (+/-)-ketamine and (+)-ketamine
      were compared in mice. At equimolar doses, the (+)-isomers elicited episodes of
      hypnosis nearly 1.4-fold more potent than those of the racemic ketamine. After
      the administration of equihypnotic doses of (+)-ketamine and (+/-)-ketamine, the
      posthypnotic stimulation of locomotor activity, stereotype behavior and 5-HT
      induced head-twitch response by the (+)-enantiomorph was significantly less
      intense than that of racemic ketamine. In receptor binding test, (+)-ketamine
      showed a higher affinity for NMDA receptor than that of (+/-)-ketamine, while (+)
      ketamine and (+/-)-ketamine showed no affinity for dopamine D2 and serotonin 5
      HT2 receptor. These results suggest that the (+)-ketamine has fewer posthypnotic
      side effects than (+/-)-ketamine when (+)-ketamine and (+/-)-ketamine were
      administered at equihypnotic dosages and that dopamine D2 and serotonin 5-HT2
      receptor were not involved in the effects of (+)-ketamine and (+/-)-ketamine.

PMID- 16289140
TI  - Effects of high sodium intake diet on the vascular reactivity to phenylephrine on
      rat isolated caudal and renal vascular beds: Endothelial modulation.
AB  - High salt intake is involved in the genesis of hypertension and vascular changes
      in salt-sensitive patients. Although many mechanisms have been proposed, the
      underlying mechanisms of these alterations in healthy rats are not completely
      elucidated. The aim of this study was to investigate if male Wistar rats fed a
      high salt diet, NaCl 1.8% in drinking water for 4 weeks, develop changes in the
      pressor reactivity of isolated tail and renal vascular beds. Salt treatment
      increased mean arterial pressure (SALT = 124 +/- 2.2 vs. CT = 111 +/- 3.9 mmHg; p
      < 0.01) and urinary sodium excretion in the absence of changes in sodium plasma
      levels. Pressor reactivity was generated in isolated tail and kidney vascular
      beds as dose-response curves to phenylephrine (PHE = 0.01 to 300 microg). SALT
      increased the reactivity (E(max): SALT = 378 +/- 15.8 vs. CT = 282 +/- 10 mmHg; p
      < 0.01) without changing the sensitivity (pD(2)) to PHE in the tail vascular bed.
      However, these parameters did not change in the renal bed. In subsequent studies
      on the isolated caudal vascular bed, we found that endothelial damage, but not L
      NAME (100 microM) or indomethacin (10 microM), abolished the increment in E(max)
      to PHE induced by SALT. On the other hand, losartan (100 microM) reduced E(max)
      in SALT to CT values. Additionally, local angiotensin-converting enzyme activity
      in segments from tail artery increased by 95%. In conclusion, 4 weeks of high
      salt diet increases blood pressure and induces specific territorial vascular
      changes in response to PHE. Results also suggest that the increment in E(max) in
      the tail vascular bed from SALT rats was endothelium-dependent and was mediated
      by the activation of the local renin-angiotensin system.

PMID- 16289141
TI  - Development of metabolic systems.
AB  - In the normal adult rodent and primate, arcuate nucleus (ARH) neurons function as
      conduits for transmitting metabolic hormonal signals into the hypothalamic
      circuitry that modulates feeding and energy expenditure. We and others have shown
      that ARH projections do not fully develop until the 3rd postnatal week in the
      rodent. This is in stark contrast to the nonhuman primate (NHP) in which ARH
      projections develop during the 3rd trimester of pregnancy. This species
      difference suggests that maternal diet and health are likely key factors for the
      development of ARH projections in the primate, whereas the postnatal environment
      (i.e., diet) would be more important in the rodent. Furthermore, pertubations in
      these circuits during critical periods of development may have long-term
      consequences on feeding behavior and body weight management. Our group has used a
      rat model of overfeeding and underfeeding specifically during the postnatal
      period to begin to investigate the metabolic adaptions that may cause
      developmental abnormalities in the hypothalamic circuitry. While the overfed
      animals become obese as adults and the underfed maintain a lean phenotype, both
      models display low basal insulin and IGFII levels as adults. Furthermore, both
      models have abnormal expression of several key genes in peripheral metabolic
      tissue that are suggestive of changes in sympathetic outflow. Human studies show
      that gestational diabetes can also contribute to the development of obesity and
      diabetes in children; however, the mechanism is unknown. Since the critical
      periods for the development of hypothalamic circuits are different between
      rodents and primates our group has begun studies using NHP model to determine if
      maternal obesity/diabetes causes abnormalities in the development of metabolic
      systems, including the brain, in the offspring. To do this we have placed female
      NHPs on either a control diet or a high fat/calorie diet to induce obesity and
      diabetes. We have characterized the onset of insulin resistance and
      hyperleptinemia in these animals over the last 2(1/2) years and have collected
      offspring. Ongoing studies will investigate the metabolic abnormalities in these
      offspring.

PMID- 16289142
TI  - Induction of apoptosis by the plant alkaloid sampangine in human HL-60 leukemia
      cells is mediated by reactive oxygen species.
AB  - Sampangine is a plant-derived copyrine alkaloid extracted from the stem bark of
      Cananga odorata. This azaoxoaporphine alkaloid primarily exhibits antifungal and
      antimycobacterial activities but also displays in vitro antimalarial activity
      against Plasmodium falciparum and it is cytotoxic to human malignant melanoma
      cells. Recently, sampangine was described as a pro-apoptotic agent, but the
      biochemical pathway leading to cell death remained unclear. Considering that
      sampangine possesses an iminoquinone moiety, potentially functioning as an
      oxidizing agent, we have investigated the implication of an oxidant stress on
      sampangine-induced cytotoxicity. We show that the treatment of human HL-60
      leukemia cells for 48 h with sampangine induced an important oxidative burst.
      Real time flow cytometry measurements indicated that the production of oxidative
      species is very rapid, within minutes following the drug addition. Quenching of
      reactive oxygen species by the antioxidants N-acetyl cystein, vitamin C and
      vitamin E abolishes the pro-apoptotic activity of sampangine. The drug-induced
      production of reactive oxygen species is associated with cell cycle perturbations
      and mitochondrial alterations. This study shed light on the mechanism of action
      of sampangine and provides novel opportunities to use azaoxoaporphine alkaloids
      as lead compounds for the design of pro-apoptotic anticancer agents.

PMID- 16289144
TI  - Selective auditory attention in 3- to 5-year-old children: an event-related
      potential study.
AB  - Behavioral and electrophysiological evidence suggests that the development of
      selective attention extends over the first two decades of life. However, much of
      this research may underestimate the attention abilities of young children. By
      providing strong, redundant attention cues, we show that sustained endogenous
      selective attention has similar effects on ERP indices of auditory processing in
      adults and children as young as 3 years old. All participants were cued to
      selectively attend to one of two simultaneously presented stories that differed
      in location (left/right), voice (male/female), and content. The morphology of the
      ERP waveforms elicited by probes embedded in the stories was very different for
      adults, who showed a typical positive-negative-positive pattern in the 300 ms
      after probe onset, and children, who showed a single broad positivity during this
      epoch. However, for 3- to 5-year-olds, 6- to 8-year-olds, and adults, probes in
      the attended story elicited larger amplitude ERPs beginning around 100 ms after
      probe onset. This attentional modulation of exogenously driven components was
      longer in duration for the youngest children. In addition, attended linguistic
      probes elicited a larger negativity 300-500 ms for all groups, indicative of
      additional attentional processing. These data show that with adequate cues, even
      children as young as 3 years old can selectively attend to one auditory stream
      while ignoring another and that doing so alters auditory sensory processing at an
      early stage. Furthermore, they suggest that the neural mechanisms by which
      selective attention affects auditory processing are remarkably adult-like by this
      age.

PMID- 16289145
TI  - Molecular evidence of sorbitol dehydrogenase in tomato, a non-Rosaceae plant.
AB  - The enzyme NAD-dependent sorbitol dehydrogenase (SDH) is well characterized in
      the Rosaceae family of fruit trees, which synthesizes sorbitol as a
      translocatable photosynthate. Expressed sequence tags of SDH-like sequences have
      also been generated from various non-Rosaceae species that do not synthesize
      sorbitol as a primary photosynthetic product, but the physiological roles of the
      encoded proteins in non-Rosaceae plants are unknown. Therefore, we isolated an
      SDH-like cDNA (SDL) from tomato (Lycopersicon esculentum Mill.). Genomic Southern
      blot analysis suggested that SDL exists in the tomato genome as a single-copy
      gene. Northern blot analysis showed that SDL is ubiquitously expressed in tomato
      plants. Recombinant SDL protein was produced and purified for enzymatic
      characterization. SDL catalyzed the interconversion of sorbitol and fructose with
      NAD (H). SDL showed highest activity for sorbitol among the several substrates
      tested. SDL showed no activity with NADP+. Thus, SDL was identified as a SDH,
      although the Km values and substrate specificity of SDL were significantly
      different from those of SDH purified from the Japanese pear (Pyrus pyrifolia), a
      Rosaceae fruit tree. In addition, tomato was transformed with antisense SDL to
      evaluate the contribution of SDL to SDH activity in tomato. The transformation
      decreased SDH activity to approximately 50% on average. Taken together, these
      results provide molecular evidence of SDH in tomato, and SDL was renamed LeSDH.

PMID- 16289146
TI  - Chemoprevention by thyme oils of Aspergillus parasiticus growth and aflatoxin
      production.
AB  - The essential oils from Thymus eriocalyx and Thymus X-porlock obtained by
      hydrodistillation were analyzed by GC/MS. The major components of T. eriocalyx
      and T. X-porlock oils were thymol (63.8, 31.7%), beta-phellandrene (13.30,
      38.7%), cis-sabinene hydroxide (8.1, 9.6%), 1,8-cineole (2, 1.7%), and beta
      pinene (1.31, 2%), respectively. Antifungal activities of the oils were studied
      with special reference to the inhibition of Aspergillus parasiticus growth and
      aflatoxin production. Minimal inhibitory (MIC) and minimal fungicidal (MFC)
      concentrations of the oils were determined. Static effects of the above oils
      against A. parasiticus were at 250 ppm and lethal effects of T. eriocalyx and T.
      X-porlock were 500 and 1000 ppm of the oils, respectively. Aflatoxin production
      was inhibited at 250 ppm of both oils with that of T. eriocalyx being stronger
      inhibitor. Transmission electron microscopy (TEM) of A. parasiticus exposed to
      MIC level (250 ppm) of the oils showed irreversible damage to cell wall, cell
      membrane, and cellular organelles. It is concluded that the essential oils could
      be safely used as preservative materials on some kinds of foods at low
      concentrations to protect them from fungal infections.

PMID- 16289147
TI  - Bioactive constituents from roots of Bursera tonkinensis.
AB  - Bioassay directed-fractionation led to isolation of 12 compounds from the roots
      of Bursera tonkinensis Guillaum (Burseraceae), including burselignan,
      bursephenylpropane, and burseneolignan. Of the 12 compounds, only 4'
      demethyldesoxypodophyllotoxin exhibited significant cytotoxic activities against
      KB, Col2 and LNCaP cell lines.

PMID- 16289148
TI  - Isolation of iridoid and secoiridoid glycosides and comparative study on Radix
      gentianae and related adulterants by HPLC analysis.
AB  - HPLC profile guided study led to the isolation of an acylated secoiridoid
      glycoside, named gentiotrifloroside (1), together with six known compounds, i.e.,
      loganic acid (2), 6-O-beta-d-glucopyranosylgentiopicroside (3), swertiamarin (4),
      gentiopicroside (5), sweroside (6) and 2 -(o,m-dihydroxybenzyl)-sweroside (7)
      from Gentiana triflora and Gentiana rigescens. The structure of 1 was deduced
      from one- and two-dimensional NMR spectroscopic experiments. Compounds 1-7 were
      used successfully as chemical markers for the comparison of the four species of
      Gentiana used as Radix gentianae. Additionally, differentiation of Gentiana
      species mentioned and those used as adulterants was evaluated. The close
      similarity of chemical composition among the four genuine Gentiana species
      explain their popular usage as R. gentianae in Chinese medicine. We have also
      shown that the variation of chemical composition in R. gentianae and related
      adulterants agree well with their botanical phylogeny.

PMID- 16289149
TI  - Essential oil composition is related to the natural habitats: Coridothymus
      capitatus and Satureja thymbra in NATURA 2000 sites of Crete.
AB  - The study of essential oils obtained from Coridothymus capitatus and Satureja
      thymbra collected from different natural habitat types of 11 NATURA 2000 sites
      scattered all over Crete has shown that they are characterized either by a high
      amount of carvacrol (up to 75.7%) or thymol (up to 65.6%) or by a more or less
      equal amount of the two phenols. The results of a discriminant analysis with
      predefined groups the natural habitat types wherefrom the plants were collected
      have shown that the oils of both species collected from the dry dwarf-shrub
      formations of the lowland have a high carvacrol content whereas those collected
      from the more mesic timber or highland formations have a high thymol content.
      Furthermore, the results of this study introduce the use of natural habitat unit
      as a tool for the assessment of essential oil variation.

PMID- 16289150
TI  - Apoplastic polyesters in Arabidopsis surface tissues--a typical suberin and a
      particular cutin.
AB  - Cutinized and suberized cell walls form physiological important plant-environment
      interfaces as they act as barriers limiting water and nutrient loss and protect
      from radiation and invasion by pathogens. Due to the lack of protocols for the
      isolation and analysis of cutin and suberin in Arabidopsis, the model plant for
      molecular biology, mutants and transgenic plants with a defined altered cutin or
      suberin composition are unavailable, causing that structure and function of these
      apoplastic barriers are still poorly understood. Transmission electron microscopy
      (TEM) revealed that Arabidopsis leaf cuticle thickness ranges from only 22 nm in
      leaf blades to 45 nm on petioles, causing the difficulty in cuticular membrane
      isolation. We report the use of polysaccharide hydrolases to isolate Arabidopsis
      cuticular membranes, suitable for depolymerization and subsequent compositional
      analysis. Although cutin characteristic omega-hydroxy acids (7%) and mid-chain
      hydroxylated fatty acids (8%) were detected, the discovery of alpha,omega-diacids
      (40%) and 2-hydroxy acids (14%) as major depolymerization products reveals a so
      far novel monomer composition in Arabidopsis cutin, but with chemical analogy to
      root suberin. Histochemical and TEM analysis revealed that suberin depositions
      were localized to the cell walls in the endodermis of primary roots and the
      periderm of mature roots of Arabidopsis. Enzyme digested and solvent extracted
      root cell walls when subjected to suberin depolymerization conditions released
      omega-hydroxy acids (43%) and alpha,omega-diacids (24%) as major components
      together with carboxylic acids (9%), alcohols (6%) and 2-hydroxyacids (0.1%).
      This similarity to suberin of other species indicates that Arabidopsis roots can
      serve as a model for suberized tissue in general.

PMID- 16289151
TI  - Dechlorodauricumine from cultured roots of Menispermum dauricum.
AB  - Dechlorodauricumine, a possible organic substrate for biochlorination, was
      isolated from cultured roots of Menispermum dauricum, a rich source of
      chlorinated alkaloids. Its structure was established by spectroscopic and
      chemical methods.

PMID- 16289152
TI  - Regulation of the catalytic activity of PTP1B: roles for cell adhesion, tyrosine
      residue 66, and proline residues 309 and 310.
AB  - The reversible phosphorylation of proteins on tyrosine residues is fundamental to
      a variety of intracellular signaling pathways and is controlled by the actions of
      protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). While
      much progress has been made in understanding the regulation of PTKs, there is
      still relatively little known concerning the regulation of PTPs. Using immune
      complex phosphatase assays, we demonstrated that the enzymatic activity of the
      nonreceptor type PTP, PTP1B, is regulated by cell adhesion. Placing primary human
      foreskin fibroblasts (HFFs) in suspension leads to a distinct increase in PTP1B
      activity, whereas the readhesion of suspended HFFs onto fibronectin or collagen I
      inhibited activity. To gain insight into the mechanisms involved, we analyzed
      recombinant forms of PTP1B mutated at potential regulatory sites. Our results
      indicated that tyrosine residue 66 is essential for maintaining activity at 37
      degrees C. We also found that the C-terminal region of PTP1B and localization to
      the endoplasmic reticulum are not required for the inhibition of activity by cell
      adhesion. However, analysis of PA-PTP1B, in which alanines are substituted for
      prolines 309 and 310, revealed an important role for these residues as the
      catalytic activity of this mutant did not decrease following readhesion onto
      collagen I. Since the binding of p130cas and Src to PTP1B is dependent upon these
      proline residues, we assayed the regulation of PTP1B in mouse embryo fibroblasts
      deficient in these proteins. We found that neither p130cas nor Src is required
      for the inhibition of PTP1B activity by adhesion to extracellular matrix
      proteins. Additionally, pretreatment with cytochalasin D did not prevent the
      reduction of PTP1B activity when cells adhered to collagen I, indicating that
      cell spreading is not required for this regulation. The control of the catalytic
      activity of PTP1B by cell adhesion demonstrated in this study is likely to have
      important implications for growth factor and insulin signaling.

PMID- 16289153
TI  - Phosphorylated l-caldesmon is involved in disassembly of actin stress fibers and
      postmitotic spreading.
AB  - The function of the ubiquitous actin-binding protein, caldesmon (l-CaD) in
      mammalian non-muscle cells remains elusive. During mitosis, l-CaD becomes
      markedly phosphorylated at Ser497 and Ser527 (in the rat sequence), therefore, it
      has been suggested that l-CaD is involved in cytokinesis by inhibiting the
      actomyosin interaction until it is phosphorylated, although direct in vivo
      evidence is still missing. In the present study, we used F-actin staining and
      specific antibodies against these two phosphorylation sites of l-CaD to
      simultaneously monitor actin assembly and l-CaD phosphorylation. Our observations
      demonstrated that the level of l-CaD phosphorylation undergoes dynamic changes
      during the cell cycle. The spatial and temporal distributions of phospho-CaD do
      not correlate with cytokinesis per se, but rather, with the level of actin
      bundles in a reciprocal manner. The highest l-CaD phosphorylation level coincides
      with the disassembly of actin cytoskeleton during mitotic cell rounding. Ser-to
      Ala mutations at these two positions prevent stress fibers from disassembly upon
      migratory stimulation. In addition, phospho-CaD appears to colocalize with
      nascent focal adhesion complexes during postmitotic spreading. These findings
      suggest that l-CaD phosphorylation plays an important role not only in
      cytoskeleton remodeling during cell shape changes, but also in cell spreading and
      migration.

PMID- 16289154
TI  - Intracellular dynamics of the Hsp90 co-chaperone p23 is dictated by Hsp90.
AB  - p23 is a component of the Hsp90 molecular chaperone machine. It binds and
      stabilizes the ATP-bound dimeric form of Hsp90. Since Hsp90 binds protein
      substrates in the ATP conformation, p23 has been proposed to stabilize Hsp90
      substrate complexes. In addition, p23 can also function as a molecular chaperone
      by itself and even possesses an unrelated enzymatic activity. Whether it fulfills
      the latter functions in cells while bound to Hsp90 remains unknown and is
      difficult to extrapolate from cell-free biochemical experiments. Using the
      "fluorescence recovery after photobleaching" (FRAP) technology, I have examined
      the dynamics of human p23, expressed as a fusion protein with the green
      fluorescent protein (GFP), in living human HeLa cells. GFP-p23 is distributed
      throughout the cell, and its mobility is identical in the cytoplasm and in the
      nucleus. When the Hsp90 interaction is disrupted either with the Hsp90 inhibitor
      geldanamycin or by introduction of point mutations into p23, the mobility of p23
      is greatly accelerated. Under these conditions, its intracellular movement may be
      diffusion-controlled. In contrast, when wild-type p23 is able to bind Hsp90, a
      more complex FRAP behavior is observed, suggesting that it is quantitatively
      bound in Hsp90 complexes undergoing a multitude of other interactions.

PMID- 16289155
TI  - Hypoxia-induced HIF-1 alpha accumulation is augmented in a co-culture of keloid
      fibroblasts and human mast cells: involvement of ERK1/2 and PI-3K/Akt.
AB  - Keloids represent a prolonged inflammatory fibrotic state with areas that display
      distinctive histological features characterized by an abundant extracellular
      matrix stroma, a local infiltration of inflammatory cells including mast cells,
      and a milieu of enriched cytokines. Previous studies from our laboratory
      demonstrated an intrinsic higher level of HIF-1alpha and VEGF protein expression
      in keloid tissues compared with their adjacent unremarkable skins. To further
      investigate the mechanisms underlying the elevated expression of HIF-1alpha and
      VEGF in keloids, we exposed a co-culture of keloid fibroblasts and mast cells
      (HMC-1) to hypoxic conditions and studied the expression of HIF-1alpha and its
      target gene, VEGF. Our results showed that hypoxia-dependent HIF-1alpha protein
      accumulation and VEGF expression is augmented in keloid fibroblasts when co
      cultured with HMC-1 cells under the condition where direct cell-cell contact is
      allowed. But such augmentation is not observed in the transwell co-culture system
      whereas fibroblasts and HMC-1 cells were separated by a porous membrane. Our
      results also indicated that the enhancement of hypoxia-mediated activation of
      ERK1/2 and Akt requires direct cell-cell interaction between mast cells and
      keloid fibroblasts, and activation of both ERK1/2 and Akt is involved in the
      hypoxia-dependent HIF-1alpha protein accumulation and VEGF expression in the co
      culture system. These findings suggest that under hypoxic conditions mast cells
      may contribute, at least in part, to an elevated expression of HIF-1alpha and
      VEGF protein in keloids via direct cell-cell interaction with fibroblasts.

PMID- 16289156
TI  - Metallothionein expression in benign and malignant canine mammary gland tumours.
AB  - The presence of metallothioneins (MTs) were demonstrated immunohistochemically
      using a monoclonal antibody (E9) against a conserved epitope of I and II isoforms
      in canine mammary tumours. In a semiquantitative analysis MT expression in the
      tumour cells was observed in 54/54 cases of benign and 32/40 malignant mammary
      neoplasms. A statistically significant difference at the level of P<0.01 was
      observed for MT expression between benign and malign mammary tumours in terms of
      immunoreactivity score. It is concluded that immunohistochemically demonstrated
      MT expression is significantly associated with benign canine mammary tumours.

PMID- 16289157
TI  - Clinical efficacy and plasma concentrations of two formulations of buparvaquone
      in cattle infected with East Coast fever (Theileria parva infection).
AB  - East Coast fever, caused by the protozoan parasite Theileria parva, kills about
      600,000 cattle annually in Africa. The hydroxynaphthoquinone compound
      buparvaquone (BPQ) is curative. Sixteen calves were infected with T. parva. On
      manifestation of disease symptoms, eight were injected with the original
      (pioneer) BPQ product and eight with a test product containing BPQ. All 16 calves
      were cured by one injection of 2.5 mg BPQ/kg bodyweight. The concentration of BPQ
      in blood plasma was monitored by HPLC. The mean observed C(max) of BPQ was 0.229
      and 0.253 microg/mL of plasma, the mean observed time to reach this concentration
      (T(max)) was 2.62 and 2.12 h and the AUC (area under curve) was 4.785 and 4.156
      microg h/mL, respectively, for the pioneer and test product. Considerable
      variations occurred in the plasma concentration of BPQ within each group. They
      showed no relationship with either clinical or parasitological parameters
      following treatment.

PMID- 16289158
TI  - Toxoplasma gondii infection in cats from Sao Paulo state, Brazil: seroprevalence,
      oocyst shedding, isolation in mice, and biologic and molecular characterization.
AB  - Cats are the most important hosts in the epidemiology of Toxoplasma gondii
      infections in humans and animals. Serologic and parasitological prevalence of T.
      gondii were determined in 237 cats from 15 counties in Sao Paulo state, Brazil.
      Antibodies to T. gondii were found in a 1:25 dilution of serum of 84 (35.4%) out
      of 237 cats by the modified agglutination test (MAT). Samples of brain, heart,
      tongue, and limb muscles (total 50 g) of 71 of the seropositive cats were pooled
      for each cat, digested in pepsin and bioassayed in mice. Faeces (1 g) from the
      rectum of each cat were examined microscopically for T. gondii-like oocysts and
      verified by bioassay in mice; T. gondii oocysts were found in the faeces of three
      (1.3%) of 237 cats. T. gondii was isolated from tissue homogenates of 47 cats.
      The DNA obtained from these 47 tissue isolates was characterized using the SAG2
      locus: 34 (72.4%) isolates were type I, 12 (25.5%) were type III and one (2.1%)
      was mixed with types I and III. No type II isolates were detected. Most (23/34)
      of the type I isolates killed all infected mice and 7 of 12 type III isolates did
      not kill infected mice. Characterization of the SAG2 locus directly from tissue
      homogenates from 37 of 46 cats was successful. Genotypes obtained from these
      primary samples were the same as those from the corresponding isolates obtained
      in mice. Genotyping of the three oocyst isolates revealed that two were type I
      and one was type III. Molecular and biologic characteristics of T. gondii
      isolates from animals from Brazil are different from those from other parts of
      the world.

PMID- 16289159
TI  - Study and culture of haematopoietic progenitor cells from peripheral blood in
      rats, hamsters and mice.
AB  - The aim of this work was to isolate and cultivate a subpopulation of pluripotent
      stem cells present in peripheral blood of different animal species, frequently
      used in laboratory studies (mice, rats and hamsters). Pluripotent stem cells
      (PSCs), already described in human beings, are fibroblast-like cells that exhibit
      a CD34 marker, specific for haematopoietic stem cells. Commonly used human
      commercial media were investigated for culturing animal PSCs. These findings
      suggest that this simple and standardized methodology may be applicable in
      several fields such as the study of the pharmacological effects of drugs on the
      haematopoietic line and the study of new strategies in cellular therapy for some
      human diseases.

PMID- 16289160
TI  - The pharmacokinetics of rituximab following an intravitreal injection.
AB  - Rituximab is a monoclonal antibody directed against the CD20 B-cell antigen and
      is approved for the treatment of B-cell lymphoma. We investigated the
      pharmacokinetics of rituximab following intravitreal administration to assess the
      feasibility of treating primary intraocular lymphoma. Intravitreal injections of
      rituximab 0.1 ml (1 mg) were performed in rabbits. Drug concentrations in the
      aqueous and vitreous humor were measured at intervals from 2 to 17 days after
      administration. The half-life of the total amount of rituximab in the two
      compartments was calculated to be 4.7 days. The aqueous and vitreous humor drug
      levels decayed in parallel maintaining an average ratio of approximately seven.
      Fitting the data to a two-compartment model yielded a clearance from the aqueous
      humor of 1.2 microl/min. The clearance was less than the reported rate of aqueous
      humor outflow indicating that elimination by this route could have been
      sufficient to account for the disappearance of the drug from the eye. The
      duration of time over which sustained levels of rituximab were achieved suggest
      that intravitreal administration warrants further investigation as an approach to
      treating vitreous and anterior chamber infiltrates in patients with primary
      intraocular lymphoma.

PMID- 16289161
TI  - Melatonin pathway: breaking the 'high-at-night' rule in trout retina.
AB  - Pineal melatonin synthesis increases at night in all vertebrates, due to an
      increase in the activity of arylalkylamine N-acetyltransferase (AANAT). Melatonin
      is also synthesized in the retina of some vertebrates and it is generally assumed
      that patterns of pineal and retinal AANAT activity and melatonin production are
      similar, i.e. they exhibit a high-at-night pattern. However, the situation in
      fish is atypical because in some cases retinal melatonin increases during the
      day, not the night. Consistent with this, we now report that light increases the
      activity and abundance of the AANAT expressed in trout retina, AANAT1, at a time
      when the activity and abundance of pineal AANAT, AANAT2, decreases. Likewise,
      exposure to darkness causes retinal AANAT protein and activity to decrease
      coincident with increases in the pineal gland. Rhythmic changes in retinal AANAT
      protein and activity are 180 degrees out of phase with those of retinal AANAT1
      mRNA; all appear to be driven by environmental lighting, not by a circadian
      oscillator. The atypical high-during-the-day pattern of retinal AANAT1 activity
      may reflect an evolutionary adaptation that optimizes an autocrine/paracrine
      signaling role of melatonin in photoadaptation and phototransduction;
      alternatively, it might reflect an adaptation that broadens and enhances aromatic
      amine detoxification in the retina.

PMID- 16289162
TI  - The identification of myocilin-associated proteins in the human trabecular
      meshwork.
AB  - Myocilin forms high molecular weight complexes in vivo presumably due to
      interaction with itself and other myocilin binding proteins. To identify myocilin
      interacting proteins, yeast 2-hybrid analysis was performed on >1x10(6) human
      trabecular meshwork cDNA clones. Coimmunoprecipitation and Far Western analysis
      were also performed on cell lysates obtained from fresh human trabecular
      meshworks or cultured human monolayer trabecular cell lines. Among the different
      methods, 46 candidate myocilin-associated proteins were identified, including
      molecules associated with the extracellular matrix, cytoskeleton, signaling, and
      metabolism. The most consistent interaction was myocilin-myocilin binding. Yeast
      2 hybrid and Far Western analysis also found an association between myocilin and
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH). None of the other candidate
      myocilin interacting proteins were identified in more than one method.
      Characterization of these potential interacting proteins may help to better
      understand the function of myocilin in the trabecular meshwork and aqueous
      outflow pathway.

PMID- 16289163
TI  - Ca++-switch induction of RPE differentiation.
AB  - Cultured retinal pigment epithelial (RPE) cells are commonly used as a model of
      the tissue to study their involvement in visual diseases. Unfortunately, cultured
      RPE often lose their differentiated phenotype reducing their usefulness as a
      model of the RPE in vivo. In this study, we used a Ca++-switch protocol to
      initiate the patterned expression of several phenotypic and functional markers of
      RPE differentiation. Cultured RPE cells from adult donors were maintained through
      at least six serial passages prior to assay to minimize their differentiated
      properties. The cells were then subjected to the Ca++-switch protocol and
      maintained at confluence for up to 4 months. Paired control and Ca++-switch cells
      were examined for phenotype, pigmentation, and the expression of tyrosinase,
      CRABP, myocilin, and bestrophin by western blot analysis. The Ca++-switch
      protocol led to a rapid restriction of N-cadherin to lateral cell borders, and to
      expression of tyrosinase by day 4. After 8 weeks, the experimental RPE monolayers
      began to accumulate visible pigment, and after 12 weeks CRABP expression was
      observed. Myocilin was observed at 4 months after the Ca++-switch but bestrophin
      was not detected at any time point. Our results suggest this protocol may drive
      epithelial morphogenesis in RPE cells. We note two specific differences in cells
      plated in low Ca++, reduced spreading on the substrate and coordinated
      development of cadherin adhesion when the Ca++-concentration is returned to
      normal. Thus, we suggest that this method produces phenotypic changes through
      multiple cell signalling pathways.

PMID- 16289164
TI  - Changes in scleral MMP-2, TIMP-2 and TGFbeta-2 mRNA expression after imposed
      myopic and hyperopic defocus in chickens.
AB  - Induction of myopia leads to a decreased glycosaminoglycan synthesis and smaller
      collagen fibrillar diameters, increased levels of gelatinase-A (MMP-2) and
      decreased amounts of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in
      the fibrous sclera of both chicks and tree shrews. Another factor found to be
      involved in altered eye growth is the transforming growth factor beta-2 (TGFbeta
      2). The aim of the current study was to measure MMP-2, TIMP-2 and TGFbeta-2 mRNA
      expression changes separately in the two scleral layers of chicks, following
      myopic and hyperopic defocus. Chicks were treated unilaterally with positive and
      negative lenses for different time periods. All contralateral eyes wore plano
      lenses and additional controls, treated binocularly with plano lenses, were
      included. Real-time PCR was used to measure MMP-2, TIMP-2 and TGFbeta-2 mRNA
      levels. Few changes in MMP-2 and TIMP-2 mRNA levels were measured following
      treatment with plus and minus lenses for up to 3 days. The mRNA levels of MMP-2
      and TIMP-2 were either unchanged or co-regulated in both eyes, even though only
      the eye with the powered lens actually displayed changes in growth. In contrast,
      TGFbeta-2 mRNA was significantly up-regulated in the cartilaginous layer
      following treatment with plus lenses after 24 hr, compared to all other groups.
      These changes were confined to the eyes that also displayed reduced growth,
      suggesting a role of TGFbeta-2 in the final steps of visual eye growth
      regulation.

PMID- 16289165
TI  - Corneal NF-kappaB activity is necessary for the retention of transparency in the
      cornea of UV-B-exposed transgenic reporter mice.
AB  - To determine the dynamics of Nuclear Factor-kappaB (NF-kappaB) in murine corneal
      pathology and the role of NF-kappaB in maintaining corneal clarity after
      ultraviolet B radiation insult, transgenic mice containing NF-kappaB-luciferase
      reporter were exposed to LPS (bacterial lipopolysaccharide), TNF-alpha (Tumor
      Necrosis Factor-alpha) or 4 kJ m(-2) UV-B radiation. NF-kappaB decoy
      oligonucleotides were also administered in some of the UV-B experiments.
      Following various exposure times, the mice were sacrificed and whole eyes or
      corneal tissues were obtained. Whole eyes were examined for scattering using a
      point-source optical imaging technique. Tissue homogenates were examined for
      luciferase activity using a luminometer. TNF-alpha and LPS-injected NF-kappaB
      luciferase transgenic mice demonstrated 3-10-fold increases in cornea NF-kappaB
      with peak activities at 4 and 6 hr post-injection, respectively. Mice exposed to
      4 kJ m(-2) UV-B exhibited a 3-fold increase in NF-kappaB activity 4 hr post
      exposure. The administration of NF-kappaB-decoy oligonucleotides to mice had the
      effect of reducing UV-B-induced NF-kappaB activity in the cornea and
      significantly increasing the amount of light scattering in UV-B exposed corneas 7
      days post-UV-B exposure when compared to sham injected mice. These results
      indicate that NF-kappaB is activated in cornea in pathologies that involves
      increased plasma levels of LPS and TNF-alpha, as well as direct UV-B exposure,
      and suggest that NF-kappaB activation play an essential part in the corneal
      healing process.

PMID- 16289166
TI  - Early treatment failure in severe malaria resulting from abnormally low plasma
      quinine concentrations.
AB  - A patient admitted with severe Plasmodium falciparum malaria in western Thailand
      had an early treatment failure with quinine, despite full dosing. Plasma quinine
      concentrations were subtherapeutic. Abnormal quinine pharmacokinetics may explain
      sporadic reports of quinine treatment failures in severe malaria.

PMID- 16289167
TI  - Electrocardiographic and biochemical adverse effects of sodium stibogluconate
      during treatment of cutaneous and mucosal leishmaniasis among returned
      travellers.
AB  - Use of parenteral pentavalent antimonials to treat leishmaniasis is associated
      with a range of cardiological, biochemical and haematological adverse effects.
      The most serious of these is the development of ventricular tachyarrhythmias
      associated with prolongation of the electrocardiographic rate-corrected QT
      interval (QTc). Whereas some studies have reported that serious cardiological and
      biochemical adverse effects are common and often require treatment interruption
      or discontinuation, others have reported the drugs to be well tolerated. We
      conducted a detailed retrospective analysis of adverse events among British
      returned travellers (n=65) with New World cutaneous or mucosal leishmaniasis who
      received i.v. sodium stibogluconate (SbV) for >or=21 days. The mean+/-SEM QTc
      progressively increased from 389+/-3.1 msec to 404+/-2.9 msec during 3 weeks of
      treatment and the QTc reached the threshold for potential cardiac toxicity among
      6 (10%) patients during the third week of treatment. Marked QTc prolongation and
      ventricular tachyarrhythmias occurred in one elderly patient with hypokalaemia
      and pre-existing cardiovascular morbidity. Although increased serum
      concentrations of amylase and hepatic transaminases were observed among 67% and
      85% of patients respectively, none developed clinical pancreatitis or hepatitis
      and treatment modification was not required. SbV can be used safely in this
      population with adequate monitoring and the need for treatment interruption is
      uncommon. Identification of factors before and during treatment that may increase
      the risk of QTc prolongation and arrhythmias is important.

PMID- 16289168
TI  - Prevalence of and risk factors for hepatitis C in rural pregnant Egyptian women.
AB  - Prevalence and risk factors for hepatitis C virus (HCV) infection were studied in
      2,587 pregnant women from three rural Egyptian villages in the Nile Delta being
      admitted to a prospective cohort study of maternal-infant transmission; 408
      (15.8%) had antibodies to HCV (anti-HCV) and 279 (10.8%) also had HCV-RNA. Fewer
      than 1% gave a history of jaundice or liver disease. Risk factors for anti-HCV
      included increasing age, low socioeconomic status and a history of blood
      transfusion or injection therapy for schistosomiasis. Sub-analyses after
      stratification of subjects by village revealed risks associated with specific
      venues for medical care, having a previous delivery attended by a traditional
      birth assistant (TBA), receiving medical care in a temporary clinic located in a
      mosque, overnight admission to a private doctor's clinic, and circumcision by a
      TBA or a 'health barber'. Our results suggest HCV causes very little detected
      illness in young adult Egyptian women and some sources of HCV transmission in
      rural Egypt in the past were associated with the provision of medical care and
      varied by location. Prevention should be focused on providing appropriate
      resources and health education should be given to formal and informal health care
      providers and should be sufficiently broad to adjust for local variations in
      exposures.

PMID- 16289169
TI  - Effects of intrathecal anandamide on somatosensory evoked responses in rats.
AB  - Anandamide, endogenous ligand of cannabinoid receptors produces similar effects
      of cannabinoids via CB1 receptors in the central nervous system. Its effect on
      ascending pathways of somatosensory conduction and somatosensory cortex is not
      known. The aim of this study was to determine the effects of anandamide on
      somatosensory evoked potentials (SEP). In this study, 24 Wistar male rats were
      used. The rats were divided into 4 groups. At the beginning, sciatic nerve
      stimulated scalp SEP traces were obtained from all of the rats. Later, 0.02 cm(3)
      anhydrous ethanol, 100 microg/kg, 200 microg/kg and 400 microg/kg anandamide
      dissolved in anhydrous ethanol were injected intrathecally to the first
      (control), second, third and fourth groups, respectively. Five minutes later,
      second SEP traces were started. In every SEP trace, two negative waves (N1, N2)
      following positive deflections were obtained. The latency and amplitudes of these
      waves assessed were compared in each group. In control and second groups, the
      parameters of these waves before and after the injections were not significantly
      different. However, in the third and fourth groups, latencies of N1 and N2 after
      injections were found significantly longer. This effect was dose dependent. In
      any of the groups, no significant changes were detected in the amplitudes after
      injections. In conclusion, anandamide, when injected intrathecally in
      pharmacological doses caused an induction of moderate conduction delay in SEP
      systems.

PMID- 16289171
TI  - Manipulating REM sleep in older adults by selective REM sleep deprivation and
      physiological as well as pharmacological REM sleep augmentation methods.
AB  - Experimental approaches to manipulate REM sleep within the cognitive neuroscience
      of sleep are usually based on sleep deprivation paradigms and focus on younger
      adults. In the present study, a traditional selective REM sleep deprivation
      paradigm as well as two alternative manipulation paradigms targeting REM sleep
      augmentation were investigated in healthy older adults. The study sample
      consisted of 107 participants, male and female, between the ages of 60 and 82
      years, who had been randomly assigned to five experimental groups. During the
      study night, a first group was deprived of REM sleep by selective REM sleep
      awakenings, while a second group was woken during stage 2 NREM sleep in matched
      frequency. Physiological REM sleep augmentation was realized by REM sleep rebound
      after selective REM sleep deprivation, pharmacological REM sleep augmentation by
      administering an acetylcholinesterase inhibitor in a double-blind, placebo
      controlled design. Deprivation and augmentation paradigms manipulated REM sleep
      significantly, the former affecting more global measures such as REM sleep
      minutes and percentage, the latter more organizational aspects such as stage
      shifts to REM sleep, REM latency, REM density (only pharmacological augmentation)
      and phasic REM sleep duration. According to our findings, selective REM sleep
      deprivation seems to be an efficient method of REM sleep manipulation in healthy
      older adults. While physiological rebound-based and pharmacological cholinergic
      REM sleep augmentation methods both failed to affect global measures of REM
      sleep, their efficiency in manipulating organizational aspects of REM sleep
      extends the traditional scope of REM sleep manipulation methods within the
      cognitive neuroscience of sleep.

PMID- 16289170
TI  - Combined delivery of neurotrophin-3 and NMDA receptors 2D subunit strengthens
      synaptic transmission in contused and staggered double hemisected spinal cord of
      neonatal rat.
AB  - We investigated whether administration of neurotrophin-3 (NT-3) and NMDA-2D
      expressing units, found previously to enhance transmission in neonatal rat spinal
      cord, strengthens synaptic connections in the injured neonatal cord. We employed
      electrophysiological methods to evaluate the strength of synaptic transmission to
      individual motoneurons in the contusion and staggered double hemisection spinal
      cord injury (SCI) models. SCI at caudal thoracic levels (T11-T12) was carried out
      at postnatal day 2 (P2). Plugs containing NT-3- secreting fibroblasts and NR2D
      expressing HSV-1 amplicons (HSVnr2d) were implanted above the lesion. Control
      animals were treated with an amplicon-expressing beta-galactosidase (HSVlac).
      After 8-10 days of treatment, the rats were sacrificed and spinal cords were
      removed for intracellular recording. Untreated contused cords preserved a
      fraction of white matter and weak monosynaptic responses were observed through
      the injury region. However, no synaptic connections were observed in control
      cords receiving double hemisection injury. Combined treatment with NT-3 and
      HSVnr2d strengthened monosynaptic connections in contused cords and induced the
      appearance of weak but functional multisynaptic connections in double hemisected
      cords. In contrast, treatment with either NT-3 or HSVnr2d alone failed to induce
      appearance of synaptic responses through the hemisected region. These results
      suggest that chronic treatment with NT-3 secreting fibroblasts combined with
      facilitated function of NMDA receptors by HSVnr2d treatment strengthens
      connections that survive incomplete SCI and therefore that such combined
      treatment might facilitate recovery of function following SCI.

PMID- 16289172
TI  - Aldosterone and the kidney: rapid regulation of renal microcirculation.
AB  - Recent studies provide evidence that aldosterone (Aldo) accelerates hypertension,
      proteinuria and glomerulosclerosis in animal models of chronic renal failure.
      Although the underlying mechanisms are not well defined, Aldo may exert these
      deleterious renal effects by elevating renal vascular resistance (RVR) and
      glomerular capillary pressure (P(GC)). To test this possibility, we studied the
      action of Aldo on rabbit afferent (Af-) and efferent arterioles (Ef-Arts),
      crucial vascular segments to the control of glomerular hemodynamics. Aldo caused
      rapid (within 5 min) constriction in both arterioles. The constriction was not
      affected by spironolactone but was reproduced by membrane-impermeable albumin
      conjugated Aldo, suggesting that vasoconstrictor actions are non-genomic. This
      notion was further supported by the finding that neither actinomycin D nor
      cycloheximide had effect. The vasoconstrictor action of Aldo on Af-Arts was
      inhibited by nifedipine (L-type calcium channel blocker), whereas that on Ef-Arts
      was inhibited by efonidipine (both L- and T-type calcium channel blocker) but not
      nifedipine. Disrupting the endothelium or nitric oxide (NO) synthesis inhibition
      augmented the vasoconstriction in Af-Arts, demonstrating that endothelium-derived
      NO modulates the vasoconstrictor actions of Aldo. Thus, Aldo causes non-genomic
      vasoconstriction via calcium mobilization thorough L- or T-type calcium channels
      in Af- or Ef-Arts, respectively. These vasoconstrictor actions on the glomerular
      microcirculation may play an important role in the pathophysiology and
      progression of renal diseases by elevating RVR and P(GC), especially when
      endothelium functions are impaired. In addition to our study, this review
      describes recent findings on the rapid cardiovascular actions of Aldo, with a
      particular attention to the renal hemodynamics.

PMID- 16289173
TI  - Non-genomic effects of the androgen receptor and vitamin D agonist are involved
      in suppressing invasive phenotype of prostate cancer cells.
AB  - Suppression of invasive phenotype is essential in developing new therapeutic
      tools to treat prostate cancer (PC). Evidence indicates that androgen-dependent
      (AD) prostate cancer cells are characterized by a lower malignant phenotype. We
      have demonstrated that transfection with an androgen receptor (AR) expression
      vector of the androgen-independent (AI) prostate cancer cell line PC3 decreases
      invasion of these cells through modulation of alpha6beta4 integrin expression,
      indicating a genotropic effect of androgens in inhibiting invasion ability of AD
      PC cells. Later on, we have shown that also a non-genotropic mechanism is
      involved in such an effect. By using immunoconfocal fluorescent microscopy, we
      demonstrated that AR in PC3-AR cells co-localizes with the EGFR receptors (EGFR)
      in PC3-AR cells. Co-immunoprecipitation studies both in PC3-AR cells and in the
      AD cell line LNCaP that physiologically express both receptors, confirm the
      occurrence of an interaction between of the two proteins. In PC3-AR cells, we
      demonstrated a disruption of EGFR signalling properties (reduced EGF-induced EGFR
      autotransphosphorylation, reduced EGF-stimulated PI3K activity as well as EGFR
      PI3K interaction) contributing to the lower invasive phenotype of these cells. In
      another study, we investigated the effects of a new Vitamin D analogue, BXL628,
      on invasion in response to KGF in the androgen-independent PC cell line DU145. We
      found that the compound was able to reduce proliferation and invasion of the
      cells in response to the growth factor. In addition, we found that KGF-induced
      autotransphosphorylation of KGF receptor (KGFR) and PI3K activation were
      suppressed after short-term (5min) pre-treatment with the analogue before
      addition of KGF. Collectively, these studies demonstrate that a non-genotropic
      effect due to a direct interaction of the androgen receptor with EGFR and to a
      rapid effect of a Vitamin D agonist on KGFR may disrupt signalling of GF leading
      to decreased tumorigenicity and a less malignant phenotype of PC cells in vitro.

PMID- 16289174
TI  - Synthesis of 7-substituted-5-androstene derivatives promoted by SmI2.
AB  - The 7-substituted-5-androstene derivatives 2a-10a and 2b-10b were prepared by
      reaction of 3beta,17beta-di(tert-butyldimethylsilyloxy)-5-androsten-7-one 1 with
      different organic halides. The resulting 7alpha- and 7beta-isomers were carefully
      separated by column chromatography. The structural assignments of the 7alpha- and
      7beta-isomers were determined by 13C-NMR.

PMID- 16289175
TI  - Identification and biochemical characterization of Leishmania strains isolated in
      Peru, Mexico, and Spain.
AB  - Eight Leishmania promastigotes were isolated from different geographical areas:
      three (LP1, LP2, and LP3) from the provincial department La Libertad and the
      fourth (LP4) from the department of Cajamarca (northern Peru); another three
      (LM1, LM2, and LM3) in the province of Campeche (Mexico); and the last (LS1) from
      a clinical case of a dog in Madrid (Spain). The isolates were characterized by
      carbohydrate cell-surface residues using agglutinations with four purified
      lectins, by isoenzyme analysis using different isoenzymes, by analysis of
      kinetoplast DNA (kDNA) restriction fragment length polymorphism using four
      different restriction endonucleases and by the final metabolite patterns after in
      vitro culture. These isolates were compared with four reference strains and
      typified as: Leishmania (Leishmania) donovani, two strains of L. (L.) infantum,
      and one species of L. (Viania) peruviana. According to our results and the
      statistical study, the Peruvian isolates represent three different strains: one
      would be L. (V.) peruviana, another the strain isolated in Cajamarca (LP4) and
      the third would include the three strains from the department of La Libertad
      (LP1, LP2, and LP3), these latter three isolates being phylogenetically closer to
      the reference strain L. (L.) donovani. Meanwhile, the three isolates from Mexico
      form a group with close phylogenetic relationships to each other. The isolate
      from Spain belongs to the species L. (L.) infantum. Thus, a close correlation was
      drawn between the identity of each strain and its geographical origin.

PMID- 16289176
TI  - Metabolism of trans, trans-muconaldehyde, a cytotoxic metabolite of benzene, in
      mouse liver by alcohol dehydrogenase Adh1 and aldehyde reductase AKR1A4.
AB  - The reductive metabolism of trans, trans-muconaldehyde, a cytotoxic metabolite of
      benzene, was studied in mouse liver. Using an HPLC-based stopped assay, the
      primary reduced metabolite was identified as 6-hydroxy-trans, trans-2,4
      hexadienal (OH/CHO) and the secondary metabolite as 1,6-dihydroxy-trans, trans
      2,4-hexadiene (OH/OH). The main enzymes responsible for the highest levels of
      reductase activity towards trans, trans-muconaldehyde were purified from mouse
      liver soluble fraction first by Q-sepharose chromatography followed by either
      blue or red dye affinity chromatography. In mouse liver, trans, trans
      muconaldehyde is predominantly reduced by an NADH-dependent enzyme, which was
      identified as alcohol dehydrogenase (Adh1). Kinetic constants obtained for trans,
      trans-muconaldehyde with the native Adh1 enzyme showed a Vmax of 2141+/-500
      nmol/min/mg and a Km of 11+/-4 microM. This enzyme was inhibited by pyrazole with
      a KI of 3.1+/-0.57 microM. Other fractions were found to contain muconaldehyde
      reductase activity independent of Adh1, and one enzyme was identified as the
      NADPH-dependent aldehyde reductase AKR1A4. This showed a Vmax of 115 nmol/min/mg
      and a Km of 15+/-2 microM and was not inhibited by pyrazole.

PMID- 16289178
TI  - Spermatozoa and spermiogenesis of Holocnemus pluchei (Scopoli, 1763) (Pholcidae,
      Araneae).
AB  - Until now, the knowledge on pholcid spermatozoa is based on two species, Pholcus
      phalangioides and, incompletely, Holocnemus pluchei. To complete this knowledge
      and to reveal more potential phylogenetic characters, we have investigated sperm
      ultrastructure and spermiogenesis of H. pluchei. We found that the sperm cells of
      this species are clearly different from those of P. phalangioides with respect
      to: (1) the lack of specialization in the cylindrical acrosomal vacuole; (2) a
      nuclear canal which is located in the periphery and not in the center of the
      nucleus; (3) a more prominent postcentriolar elongation of the nucleus; (4) the
      presence of "inner microtubules" in the implantation fossa in early and mid
      spermatids; (5) the absence of a helical band of nuclear material; (6) the
      proximal centriole which is not prolonged; (7) the types of secretion in the
      seminal fluid (only two types in H. pluchei). Similarities in the spermatozoa of
      both species concern: (1) a large implantation fossa which contains large amounts
      of glycogen in mature spermatozoa; (2) absence of a centriolar adjunct; (3) an
      axonemal basis located in the posterior part of the implantation fossa; (4) the
      formation of the so-called cleistospermia in the vas deferens. Our results
      strongly support systematic relationships within Pholcidae placing these two
      species in different subgroups.

PMID- 16289177
TI  - Below background levels of blood lead impact cytokine levels in male and female
      mice.
AB  - A number of studies have documented that Pb exerts immunotoxic effects on T
      lymphocytes. In studies designed to explore this general response over a broad
      dose range, female Swiss mice were administered six different diets containing Pb
      acetate 1 day after mating. During lactation, the mothers received the same feed
      given during pregnancy, and the same diets were administered to the offspring for
      9 months after weaning. At the end of exposure, blood Pb level in the offspring
      was determined, and possible changes in two type 1 cytokines (IL-2, INF-gamma)
      and one type 2 cytokine (IL-4) in the serum were measured. At higher dietary Pb
      levels (40 and 400 ppm), a significant increase in IL-4 production was associated
      with a profound decrease in INF-gamma and IL-2 production. At the lowest Pb diet
      level (0.02 ppm), which resulted in a blood lead level of (0.8 microg/dL), which
      is below background (2-3 microg/dL) values in humans, increases in INF-gamma and
      IL-2 production along with a significant decrease in IL-4 production were
      observed. The findings provide evidence of a reversal of lead-induced cytokine
      skewing depending on the blood lead concentration. As blood lead concentration
      increases, there is a notable skewing toward Th2, while the pattern is reversed
      favoring Th1 development at lower blood lead values. The present findings are
      also notable since they indicate the potential for dietary Pb to have significant
      biological effects below normal background concentrations.

PMID- 16289179
TI  - Properties and cDNA cloning of an antihemorrhagic factor (HSF) purified from the
      serum of Trimeresurus flavoviridis.
AB  - Habu serum factor (HSF) is a metalloproteinase inhibitor that is isolated from
      the serum of habu snake (Trimeresurus flavoviridis), and it can suppress snake
      venom-induced hemorrhage. In the present study, the inhibitory property and
      fundamental structure of HSF were analyzed in detail. HSF inhibited all the
      hemorrhagic and most of the non-hemorrhagic metalloproteinases tested from the
      venoms of T. flavoviridis and Gloydius halys brevicaudus. HSF was extremely
      stable in a broad range of temperature and pH, and the treatments with a
      temperature of 100 degrees C or pH ranging from 1 to 13 barely affects its
      reactivity against G. halys brevicaudus H6 protease. Gel filtration
      chromatography revealed that HSF binds to the H6 protease with a 1:1 molar ratio.
      A secondary structure profile of HSF that was monitored by circular dichroism
      spectrum remained unvaried up to 2 M urea. The activity of HSF was
      stoichiometrically abolished by chemical modification with 2,4,6-trinitrobenzene
      sulfonic acid and N-bromosuccinimide; this indicates that Lys and Trp residues in
      its sequence play a role in the inhibitory mechanism. In this study, the amino
      acid sequence of HSF that was obtained by cDNA cloning was identical to that
      reported previously, except for five substitutions. We concluded that these
      discrepancies reflect a difference in the places of capture of the snake
      specimens.

PMID- 16289180
TI  - Amnesic shellfish poisoning toxins in bivalve molluscs in Ireland.
AB  - In December 1999, domoic acid (DA) a potent neurotoxin, responsible for the
      syndrome Amnesic Shellfish Poisoning (ASP) was detected for the first time in
      shellfish harvested in Ireland. Two liquid chromatography (LC) methods were
      applied to quantify DA in shellfish after sample clean-up using solid-phase
      extraction (SPE) with strong anion exchange (SAX) cartridges. Toxin detection was
      achieved using photodiode array ultraviolet (LC-UV) and multiple tandem mass
      spectrometry (LC-MS(n)). DA was identified in four species of bivalve shellfish
      collected along the west and south coastal regions of the Republic of Ireland.
      The amount of DA that was present in three species was within EU guideline limits
      for sale of shellfish (20 microg DA/g); mussels (Mytilus edulis), <1.0 microg
      DA/g; oysters (Crassostrea edulis), <5.0 microg DA/g and razor clams (Ensis
      siliqua), <0.3 microg DA/g. However, king scallops (Pecten maximus) posed a
      significant human health hazard with levels up to 240 microg DA/g total tissues.
      Most scallop samples (55%) contained DA at levels greater than the regulatory
      limit. The DA levels in the digestive glands of some samples of scallops were
      among the highest that have ever been recorded (2,820 microg DA/g).

PMID- 16289182
TI  - Evolution of melanocortin systems in fish.
AB  - Proopiomelanocortin (POMC) is a common precursor of melanocortin (MC), the
      collective term for adrenocorticotropic hormone (ACTH) and melanophore
      stimulating hormone (MSH), and of beta-endorphin (beta-END). Over the past
      decade, considerable progress has been made in the analysis of the POMC gene from
      a board taxonomic group of vertebrates and invertebrates. The results suggest
      that three MSHs (alpha-, beta-, and gamma-MSH) and a single END were established
      in ancestral invertebrates. Thereafter, unequal crossing over may have resulted
      in class-specific numbers of MSH segments during the radiation of fish. Moreover,
      duplication of the entire POMC gene may have led to the differentiation of POMC
      as shown in lampreys; one of the two subtypes is a precursor for ACTH and beta
      END, the other is a precursor for two forms of MSH and the other form of beta
      END. On the other hand, at least five subtypes of MC receptor (MCR) have been
      observed in fish. These are G-protein-coupled receptors with seven transmembrane
      domains. The ancestral MCR is suggested to have appeared before vertebrates, and
      then MCRs may have diverged by genome duplication and local duplication of each
      receptor gene during the evolution of vertebrates. They are distributed in many
      tissues in rather a subtype-specific manner and are responsible for a variety of
      biological functions. Thus, MC systems may have diverged by producing
      structurally different MC peptides from POMC and expressing MCR subtypes
      differing in ligand selectivity in a variety of tissues.

PMID- 16289181
TI  - Production of isodomoic acids A and B as major toxin components of a pennate
      diatom Nitzschia navis-varingica.
AB  - In order to obtain more detailed information on the distribution of domoic acid
      producing Nitzschia in Asian waters, Nitzschia-like diatoms were isolated
      primarily from the Philippines and established in culture for analysis by HPLC
      with fluorescence detection. Out of 58 isolates, 35 Nitzschia-like diatoms from
      the estuary areas of San Pedro Bay, Tacloban City and Manila Bay showed
      significant levels of domoic acid production (1.3-5.6pg/cell). These were
      identified as Nitzschia navis-varingica. Two isolates from the same locality did
      not produce domoic acid. Of the 21 isolates from Bulacan Estuary, Manila Bay,
      none produced domoic acid. They did, however, produce two substances that seemed
      to be domoic acid derivatives. One of the strains was mass cultured and the
      substances were extracted, purified and analyzed by LC-MS/MS, proton and (13)C
      NMR, and UV spectra. The produced substances were determined as isodomoic acids A
      and B. This is the first report of a diatom that produces isodomoic acids A and B
      as major toxin components.

PMID- 16289183
TI  - Seasonal changes in expression of LH-beta and FSH-beta in male and female three
      spined stickleback, Gasterosteus aculeatus.
AB  - In teleost fishes, like in other vertebrates, the gonadal development is
      stimulated by two gonadotropic hormones; luteinizing hormone (LH) and follicle
      stimulating hormone (FSH). To achieve a better understanding of the role of
      gonadotropins in teleost reproduction; expression of LH-beta and FSH-beta mRNA
      and the status of gonads and secondary sexual characters were analyzed over the
      annual cycle in male and female three-spined sticklebacks, a species in which the
      development of male secondary sexual characters and spermatogenesis are separated
      in time. The kidney in the male stickleback hypertrophies during the breeding
      season and produces a glue used when building nests. Kidney weights, as well as
      levels of 11-ketotestosterone (11KT), reached a peak in May. Both testosterone
      (T) levels and the gonadosomatic index (GSI, gonad weight/body weight x 100) in
      females started to increase in April, and peaked in May as well. Later in summer,
      after the breeding season, these features declined. In females, LH-beta
      expression followed the GSI and T levels closely, levels were low during winter
      and early spring, increased to a peak in late May and declined to low levels
      again in July. FSH-beta expression peaked earlier, in January and declined slowly
      over spring. In males, LH-beta expression peaked in May. During June-September,
      when spermatogenesis was active, LH-beta levels were very low. FSH-beta
      expression peaked in January, earlier than LH-beta expression did, and reached
      the lowest levels in July. Thus, when spermatogenesis started at the end of
      summer, the expression of both GTH-beta mRNAs, and circulating 11KT, displayed
      their lowest levels.

PMID- 16289184
TI  - Construction and characterization of an infectious molecular clone of HIV-1
      subtype A of Indian origin.
AB  - India has the second highest number of HIV-1 infected people next to South
      Africa. The predominant proportion of HIV-1 circulating in India is of subtype C
      origin, with a small fraction made up of subtypes A and B. In this report, we
      describe the construction and characterization of the first full-length
      infectious molecular clone p1579A-1 HIV-1, from an HIV-1 subtype A infected
      person from India, using long PCR and successive ligation of the amplimers.
      Phylogenetic analysis of the sequence of the entire proviral DNA and LTR
      confirmed p1579A-1 to be an HIV-1 subtype A. Analysis of the env gene of p1579A-1
      showed a conserved GPGQ motif and the absence of basic amino acids at positions
      11 and 25 suggesting CCR5 coreceptor usage. Analysis of env N-linked
      glycosylation sites revealed fewer sites in the V1 region of envelope compared to
      other subtype A. Transcription factor binding site analysis of the LTR sequences
      identified conserved as well as unique transcription factor binding sites (TFBS)
      in p1579A-1. This infectious clone of HIV-1 can be useful to study the molecular
      mechanism of dominance of subtype C in India.

PMID- 16289185
TI  - Phylogenetic analysis of rabbit haemorrhagic disease virus strains from the
      Arabian Peninsula: did RHDV emerge simultaneously in Europe and Asia?
AB  - Rabbit haemorrhagic disease virus (RHDV) emerged in 1984 in China and
      subsequently a single strain apparently dispersed worldwide killing millions of
      rabbits. Two isolates that caused outbreaks in Saudi Arabia and Bahrain have been
      sequenced and analysed phylogenetically. The Saudi Arabian lineage is directly
      descended from the Chinese strain, but the Bahrain isolate occupies a distinct
      and more divergent lineage than the Chinese virus implying that epidemic RHDV
      strains have emerged at least twice during the past 20 years and are co
      circulating in both domestic and wild rabbits.

PMID- 16289186
TI  - Energetics of arsenate sorption on amorphous aluminum hydroxides studied using
      flow adsorption calorimetry.
AB  - Flow adsorption calorimetry was used to investigate the energetics of arsenate
      sorption on amorphous aluminum hydroxide (AHO) and its effect on surface charge
      and ion exchange. Arsenate sorption at pH 5.7 was exothermic and the molar heats
      of adsorption were quite variable, ranging from -3.0 to -66 kJ/mol. Repetitive
      exposure of the same sample to arsenate in the calorimeter showed that the AHO
      was able to regenerate a considerable amount of reactive surface over time
      periods as short as 15 to 20 min. The large variability in heats of arsenate
      adsorption and the ability to regenerate reactive surface is believed to result
      from the amorphous nature of the AHO used. Heats of Cl/NO3 exchange were much
      smaller and more consistent, ranging from about 3.0 to 6.0 kJ/mol. The molar
      ratio of exchangeable Cl:Al was about 6:1 for the AHO, indicating a highly porous
      material. At pH 5.7, arsenate sorption neutralized surface positive charge as
      measured by Cl/NO3 exchange. Only at the two highest loadings (>60,000 mg/kg) did
      arsenate sorption result in any negative surface charge as measured by Na/K
      exchange. These results showed that most of the arsenate was adsorbed by a
      mechanism that involved no increase in surface negative charge. The PZNC of the
      AHO decreased by about 1 pH unit when exposed to arsenate in the flow
      calorimeter. Exposure to arsenate in a batch system decreased the PZNC about 4 pH
      units. This difference in behavior between batch and flow systems was related to
      differences in the amount of arsenate adsorbed.

PMID- 16289187
TI  - Computer simulations of surfactant monolayers at solid walls.
AB  - A series of molecular dynamics simulations to study the structure of a surfactant
      monolayer near real surfaces was carried out. A comparison of two different
      surfaces, TiO2 and SiO2, with the same monolayer was performed. Moreover, each
      surface was modeled by two different approaches, the first model considers the
      complete structure of a TiO2 (or SiO2) wall, whereas the second model is a
      continuous solid wall with an effective potential. Both wall models give
      essentially the same monolayer configuration suggesting that the explicit form of
      the wall does not play a relevant role to study the structure of surfactant
      monolayers close to planar surfaces.

PMID- 16289188
TI  - Electrokinetic behavior and colloidal stability of polystyrene latex coated with
      ionic surfactants.
AB  - This work is focused on analyzing the electrokinetic behavior and colloidal
      stability of latex dispersions having different amounts of adsorbed ionic
      surfactants. The effects of the surface charge sign and value, and the type of
      ionic surfactant were examined. The analysis of the electrophoretic mobility
      (mu(e)) versus the electrolyte concentration up to really high amounts of salt,
      much higher than in usual studies, supports the colloidal stability results. In
      addition, useful information to understand the adsorption isotherms was obtained
      by studying mu(e) versus the amount of the adsorbed surfactant. Aggregation
      studies were carried out using a low-angle light scattering technique. The
      critical coagulation concentrations (ccc) of the particles were obtained for
      different surfactant coverage. For latex particles covered by ionic surfactants,
      the electrostatic repulsion was, in general, the main contribution to the
      colloidal stability of the system; however, steric effects played an important
      role in some cases. For latices with not very high colloidal stability, the
      adsorption of ionic surfactants always improved the colloidal stability of the
      dispersion above certain coverage, independently of the sign of both, latex and
      surfactant charge. This was in agreement with higher mobility values. Several
      theoretical models have been applied to the electrophoretic mobility data in
      order to obtain different interfacial properties of the complexes (i.e., zeta
      potential and density charge of the surface charged layer).

PMID- 16289189
TI  - Interpretation of the ultrasonic effect on induction time during BaSO4
      homogeneous nucleation by a cluster coagulation model.
AB  - The effects of power ultrasound on the induction time of BaSO4 are studied
      experimentally and theoretically. In the experiments, barium sulfate is
      precipitated by mixing aqueous BaCl2 solution and Na2SO4 solution. The induction
      time is identified and measured by recording the change of turbidity in solution.
      Various energy inputs are used to investigate the effect of energy on nucleation.
      The results show that the induction time decreases with increasing
      supersaturation and increasing energy input. Employing the classical nucleation
      theory, the interfacial tension is estimated. In addition, the ultrasonic effects
      on nucleation order (n) and the nucleation coefficient (kN) are also
      investigated. A cluster coagulation model, which brings together the current
      nucleation models and the theories describing the behavior of colloidal
      suspensions, was applied to estimate the induction time under various energy
      inputs. A comparison between the results of model and the results of experiments
      shows that the number of monomers in dominating clusters (g) in the solution
      remains constant with increasing of energy input.

PMID- 16289190
TI  - The effect of the size of raw Gd(OH)3 precipitation on the crystal structure and
      PL properties of Gd2O3:Eu.
AB  - Our experiments show that cetyltrimethylammonium bromide (CTAB) has an obvious
      effect on the particle size of the precipitation of Gd(OH)3. Without CTAB, the
      particle size of the Gd(OH)3 precipitation is about 50 nm, whereas with CTAB, the
      particle size is less than 5 nm. We propose a mechanism where CTAB micelles work
      as a catalyst for the nucleation process and result in the precipitation of 5 nm
      particles. These small particles, after heat treatment at 1073 K, did not result
      in small Gd2O3 nanoparticles of the same size, but instead, forming crystals of
      30-80 nm size in both cubic and monoclinic phases. When monitoring the
      photoluminescence (PL) peak at 610 nm, we found that the charge transfer state
      (CTS) absorption amplitude of Eu-O is reduced in the mixed structures. We
      speculate that the mixed structures modify the surface properties of the Gd2O3:Eu
      nanoparticles, leading to the reduction of Eu-O CTS absorption.

PMID- 16289191
TI  - Characterization of mixed micelles of cationic twin tail surfactants with
      phospholipids using fluorescence spectroscopy.
AB  - The pyrene fluorescence measurements have been carried out for various binary
      mixtures of micelle forming (L-alpha-diheptanoylphosphatidycholine, DHPC) and
      vesicle forming (L-alpha-dimyristoylphosphatidycholine, DMPC) phospholipids with
      different twin tail alkylammonium surfactants. The mixed micelle formation in all
      binary mixtures has been evaluated and it has been observed that the mixed
      micelle formation between the unlike components of phospholipid and cationic
      surfactants takes place due to the synergistic interactions. The influence of
      hydrophobicity of series of twin tail cationic surfactants has been studied on
      the degree of synergism.

PMID- 16289192
TI  - The effect of membrane potential on the development of chemical osmotic pressure
      in compacted clay.
AB  - When clay soils are subjected to salt concentration gradients, various
      interrelated processes come into play. It is known that chemical osmosis induces
      a water flow and that a membrane potential difference develops that counteracts
      diffusive flow of solutes and osmotic flow of water. In this paper, we present
      the results of experiments on the influence of membrane potential on chemical
      osmotic flow and diffusion of solutes and we show how we are able to derive the
      membrane potential value from theory. Moreover, the simultaneous development of
      water pressure, salt concentration and membrane potential difference are
      simulated using a model for combined chemico-electroosmosis in clays. A new
      method for short-circuiting the clay sample is employed to assess the influence
      of electrical effects on flow of water and transport of solutes.

PMID- 16289193
TI  - Sorption of nitroaromatic compounds to synthesized organoclays.
AB  - This project quantifies the ability of seven engineered organoclays to sorb TNT
      and two of its reduction products: 2-amino-4,6-dinitrotoluene (2-A-4,6-DNT) and 4
      amino-2,6-dinitrotoluene (4-A-2,6-DNT). The organoclays used in the TNT sorption
      studies were synthesized in the laboratory by combining bentonite with
      benzyltriethylammonium chloride (BTEA) at 50, 75, and 100% of the bentonite's
      cation exchange capacity and with hexadecyltrimethylammonium bromide (HDTMA) at
      25, 50, 75, and 100% of the bentonite's cation exchange capacity. For sorption of
      2-A-4,6-DNT and 4-A-2,6-DNT, two organoclays were tested: BTEA at 50% CEC and
      HDTMA at 75% CEC. Sorption data with HDTMA organoclay and TNT were fit to linear
      isotherms and demonstrated that the clay's sorptive capacity increased as the
      amount of total organic carbon exchanged onto the clay increased. Sorption data
      with BTEA organoclay and TNT were fit to Langmuir isotherms; however, the clay's
      sorptive capacity increased as the amount of total organic carbon sorbed to the
      clay's surface was decreased. Sorption behavior for TNT reduction products 2-A
      4,6-DNT and 4-A-2,6-DNT to one HDTMA organoclay and one BTEA organoclay
      demonstrated that HDTMA organoclay at 10.3% total organic carbon was a more
      effective sorbent than BTEA organoclay at 5.2% total organic carbon.

PMID- 16289194
TI  - Study of low-frequency ultrasonic cavitation fields based on spectral analysis
      technique.
AB  - A kind of new spectral analysis method for analyzing ultrasonic cavitation fields
      is brought forward in this paper. This method extracts the line spectrum and the
      continuous spectrum from the cavitation noise spectrum respectively, then obtains
      estimations of the energy intensities of different cavitation components such as
      the stable cavitation and the transient cavitation through corresponding
      calculations. The method is also applied to investigate low-frequency ultrasonic
      cavitation fields and is compared with spectral level analysis method. The
      results show that this method can provide adequate information on the course of
      the cavitation process, give the delicate analysis on the transient cavitation
      and the stable cavitation, and help to gain an insight into the nonlinear process
      of cavitation fields. Moreover, it also shows that the criterion for
      characterization of cavitation intensity presented by Frohly through studying the
      high-frequency ultrasonic fields can be used to evaluate the low-frequency
      ultrasonic fields.

PMID- 16289195
TI  - Study on the Langevin piezoelectric ceramic ultrasonic transducer of longitudinal
      flexural composite vibrational mode.
AB  - In this paper, the Langevin longitudinal-flexural composite mode piezoelectric
      ultrasonic transducer is studied. This type of transducers consists of slender
      metal rods and longitudinally polarized piezoelectric ceramic rings. The
      resonance frequency equations for the longitudinal and flexural vibrations in the
      transducer are derived. By correcting the length of the metal slender rods, the
      simultaneous resonance of the longitudinal and flexural vibrations in the
      transducer is acquired. The experimental results show that the measured resonance
      frequencies of the transducers are in good agreement with the computed ones, and
      the measured resonance frequencies of the longitudinal and the flexural
      vibrations in the composite transducers are also in good agreement with each
      other.

PMID- 16289196
TI  - High resolution fundus imaging by confocal scanning laser ophthalmoscopy in the
      mouse.
AB  - We evaluated fundus imaging using a modified confocal scanning laser
      ophthalmoscope (cSLO) in mice. Examinations were performed in conscious,
      untrained mice. The largest field of view measured 1,520 x 1,520 mu, with a
      significant interindividual variability, itself correlated to biometric
      variability. The composite field of view extended up to the ora serrata. The
      reflectance imaging associated light reflection from nerve fiber bundles and
      vessel walls, and absorption by hemoglobin and melanin. Light absorption by the
      pigment epithelium indeed increased the contrast of the nerve fiber layer, but
      impaired viewing of the choroid. Due to the confocal mode, fluorescence
      angiograms with clear separation of retinal and choroidal fluorescence could be
      obtained even in albino mice. Micrometric-scale transverse resolution and several
      planes of optical sectioning within the retina were obtained. This permitted for
      instance tridimensional, subcellular viewing of gfp-expressing retinal microglial
      cells in CX(3)CR1 mice. We concluded that cSLO is a promising tool for
      noninvasive, multimodal intravital microscopy of the fundus in the mouse.

PMID- 16289197
TI  - Singularities in the inverse modeling of 2AFC contrast discrimination data.
AB  - Analytical calculations show that two-alternative force-choice data are not
      always suitable for specifying the parameters of the underlying discrimination
      model. Experimentally, we show here that in the case of contrast discrimination
      in humans, a variety of models spanning a large range of parameters can explain
      the data within an experimental error. Monte-Carlo simulations indicate that the
      number of trials in psychophysical experiments is not the limiting factor in
      estimating the parameters in contrast discrimination. These results can therefore
      explain the contradictory conclusions made by different groups about the
      relationship between the response to contrast and the noise amplitude.

PMID- 16289198
TI  - Pulse-step models of control strategies for dynamic ocular accommodation and
      disaccommodation.
AB  - Dynamic properties and control strategies of step responses by accommodation and
      disaccommodation differ from one another. Peak velocity of accommodation
      increases with response magnitude, while peak velocity and peak acceleration of
      disaccommodation increase with starting position. These dynamic properties can be
      modeled as control strategies that use independent acceleration-pulse and
      velocity-step components that are integrated respectively into phasic-velocity
      signals that control movement and tonic-position signals that control magnitude.
      Accommodation is initiated toward its final destination by an acceleration-pulse
      whose width increases with response magnitude to increase peak velocity.
      Disaccommodation is initiated toward a default destination (the far point) by an
      acceleration-pulse whose height increases with dioptric distance of the starting
      position to increase peak velocity and peak acceleration. Both responses are
      completed and maintained by tonic-position signals whose amplitudes are
      proportional to the final destination. Mismatched amplitudes of phasic-velocity
      and tonic-position signals in disaccommodation produce unstable step responses.

PMID- 16289199
TI  - Saliency from orthogonal velocity component in texture segregation.
AB  - We found that a moving target line, more-vertical than 45 deg-oriented background
      lines, pops-out (d'=1.2) although it moves at the same speed of background
      elements and although it is invisible in static presentation (d'=.7). We suggest
      that the moving more-vertical target is more salient because the motion system
      responds to the orthogonal-velocity-component (V(perpendicular)=Delta d/Delta t
      sin theta) that is larger for the more-vertical target than for distracters.
      However, motion does not produce high d' when the target is more horizontal than
      background (d'=.6). This result is not expected if saliency resulted from the sum
      of saliency of orientation and motion independently coded but is instead
      predicted by visual search asymmetry. A line length effect on the moving target
      saliency also suggests that V(perpendicular) is extracted on the whole line and
      this operation is facilitated by line length in the same way for more-vertical
      and more-horizontal targets. Altogether, these results demonstrate that speed
      based segmentation operating on V(perpendicular) not only affects speed and
      direction of motion discrimination, as previously demonstrated, but accounts for
      high saliency of image features that would otherwise prove undetectable of the
      basis of orientation-contrast.

PMID- 16289200
TI  - Resolution for spatial segregation and spatial localization by motion signals.
AB  - We investigated two types of spatial resolution for perceiving motion-defined
      contours: grating acuity, the capacity to discriminate alternating stripes of
      opposed motion from transparent bi-directional motion; and alignment acuity, the
      capacity to localize the position of motion-defined edges with respect to
      stationary markers. For both tasks the stimuli were random noise patterns, low
      pass filtered in the spatial dimension parallel to the motion. Both grating and
      alignment resolution varied systematically with spatial frequency cutoff and
      speed. Best performance for grating resolution was about 10 c/deg (for unfiltered
      patterns moving at 1-4 deg/s), corresponding to a stripe resolution of about 3'.
      Grating resolution corresponds well to estimates of smallest receptive field size
      of motion units under these conditions, suggesting that opposing signals from
      units with small receptive fields (probably located in V1) are contrasted
      efficiently to define edges. Alignment resolution was about 2' at best, under
      similar conditions. Whereas alignment judgment based on luminance-defined edges
      is typically 3-10 times better than resolution, alignment based on motion-defined
      edges is only 1.1-1.5 times better, suggesting motion contours are less
      effectively encoded than luminance contours.

PMID- 16289201
TI  - Crystal structure of cone arrestin at 2.3A: evolution of receptor specificity.
AB  - Arrestins play a fundamental role in the regulation and signal transduction of G
      protein-coupled receptors. Here we describe the crystal structure of cone
      arrestin at 2.3A resolution. The overall structure of cone visual arrestin is
      similar to the crystal structures of rod visual and the non-visual arrestin-2,
      consisting of two domains, each containing ten beta-sheets. However, at the
      tertiary structure level, there are two major differences, in particular on the
      concave surfaces of the two domains implicated in receptor binding and in the
      loop between beta-strands I and II. Functional analysis shows that cone arrestin,
      in sharp contrast to its rod counterpart, bound cone pigments and non-visual
      receptors. Conversely, non-visual arrestin-2 bound cone pigments, suggesting that
      it may also regulate phototransduction and/or photopigment trafficking in cone
      photoreceptors. These findings indicate that cone arrestin displays structural
      and functional features intermediate between the specialized rod arrestin and the
      non-visual arrestins, which have broad receptor specificity. A unique functional
      feature of cone arrestin was the low affinity for its cognate receptor, resulting
      in an unusually rapid dissociation of the complex. Transient arrestin binding to
      the photopigment in cones may be responsible for the extremely rapid regeneration
      and reuse of the photopigment that is essential for cone function at high levels
      of illumination.

PMID- 16289202
TI  - Cryo-electron microscopy reveals conserved and divergent features of gag packing
      in immature particles of Rous sarcoma virus and human immunodeficiency virus.
AB  - Retrovirus assembly proceeds via multimerisation of the major structural protein,
      Gag, into a tightly packed, spherical particle that buds from the membrane of the
      host cell. The lateral packing arrangement of the human immunodeficiency virus
      type 1 (HIV-1) Gag CA (capsid) domain in the immature virus has been described.
      Here we have used cryo-electron microscopy (cryo-EM) and image processing to
      determine the lateral and radial arrangement of Gag in in vivo and in vitro
      assembled Rous sarcoma virus (RSV) particles and to compare these features with
      those of HIV-1. We found that the lateral packing arrangement in the vicinity of
      the inner sub-domain of CA is conserved between these retroviruses. The curvature
      of the lattice, however, is different. RSV Gag protein adopts a more tightly
      curved lattice than is seen in HIV-1, and the virions therefore contain fewer
      copies of Gag. In addition, consideration of the relationship between the radial
      position of different Gag domains and their lateral spacings in particles of
      different diameters, suggests that the N-terminal MA (matrix) domain does not
      form a single, regular lattice in immature retrovirus particles.

PMID- 16289203
TI  - Crystal structure of the human LRH-1 DBD-DNA complex reveals Ftz-F1 domain
      positioning is required for receptor activity.
AB  - The DNA-binding and ligand-binding functions of nuclear receptors are localized
      to independent domains separated by a flexible hinge. The DNA-binding domain
      (DBD) of the human liver receptor homologue-1 (hLRH-1), which controls genes
      central to development and metabolic homeostasis, interacts with monomeric DNA
      response elements and contains an Ftz-F1 motif that is unique to the NR5A nuclear
      receptor subfamily. Here, we present the 2.2A resolution crystal structure of the
      hLRH-1 DBD in complex with duplex DNA, and elucidate the sequence-specific DNA
      contacts essential for the ability of LRH-1 to bind to DNA as a monomer. We show
      that the unique Ftz-F1 domain folds into a novel helix that packs against the DBD
      but does not contact DNA. Mutations expected to disrupt the positioning of the
      Ftz-F1 helix do not eliminate DNA binding but reduce the transcriptional activity
      of full-length LRH-1 significantly. Moreover, we find that altering the Ftz-F1
      helix positioning eliminates the enhancement of LRH-1-mediated transcription by
      the coactivator GRIP1, an action that is associated primarily with the distantly
      located ligand-binding domain (LBD). Taken together, these results indicate that
      subtle structural changes in a nuclear receptor DBD can exert long-range
      functional effects on the LBD of a receptor, and significantly impact
      transcriptional regulation.

PMID- 16289204
TI  - Genetic mapping of the cold-adapted phenotype of B/Ann Arbor/1/66, the master
      donor virus for live attenuated influenza vaccines (FluMist).
AB  - Cold adapted (ca) B/Ann Arbor/1/66 is the master donor virus for the influenza B
      (MDV-B) vaccine component of the live attenuated influenza vaccine (FluMist). The
      six internal genes contributed by MDV-B confer the characteristic cold-adapted
      (ca), temperature-sensitive (ts) and attenuated (att) phenotypes to the vaccine
      strains. Previously, it has been determined that the PA and NP segments of MDV-B
      control the ts phenotype while the att phenotype requires the M segment in
      addition to PA and NP. Here, we show that the PA, NP and PB2 segments are
      responsible for the ca phenotype of MDV-B when examined in chicken cell lines.
      Five loci in three RNA segments, R630 in PB2, M431 in PA and A114, H410 and T509
      in NP, are sufficient to allow efficient virus growth at 25 degrees C.
      Substitution of these five amino acids with wt (wild type) residues completely
      reverted the MDV-B ca phenotype. Conversely, introduction of these five ca amino
      acids into B/Yamanashi/166/98 imparted the ca phenotype to this heterologous wt
      virus. In addition, we also found that the MDV-B M1 gene affected virus
      replication in chicken cells at 33 and 37 degrees C. Recombinant viruses
      containing the two MDV-B M1 residues (Q159, V183) replicated less efficiently
      than those containing wt M1 residues (H159, M183) at 33 and 37 degrees C,
      implicating the role of the MDV-B M segment to the att phenotype. The complexity
      of the multigenic signatures controlling the ca, ts and att phenotypes of MDV-B
      provides the molecular basis for the observed genetic stability of the FluMist
      vaccines.

PMID- 16289206
TI  - Contour interactions between pairs of Gabors engaged in binocular rivalry reveal
      a map of the association field.
AB  - A psychophysical study was conducted to investigate contour interactions (the
      'association field'). Two Gabor patches were presented to one eye, with random
      dot patches in corresponding locations of the other eye so as to produce
      binocular rivalry. Perceptual alternations of the two rivalry processes were
      monitored continuously by observers and the two time series were cross
      correlated. The Gabors were oriented collinearly, obliquely, or orthogonally, and
      spatial separation was varied. A parallel condition was also included.
      Correlation between the rivalry processes strongly depended on separation and
      relative orientation. Correlations between adjacent collinear Gabors was near
      perfect and reduced with spatial separation and as relative orientation departed
      from collinear. Importantly, variations in cross-correlation did not alter the
      rivalry processes (average dominance duration, and therefore alternation rate,
      was constant across conditions). Instead, synchronisation of rivalry oscillations
      accounts for the correlation variations: rivalry alternations were highly
      synchronised when contour interactions were strong and were poorly synchronised
      when contour interactions were weak. The level of synchrony between these two
      stochastic processes, in depending on separation and relative orientation,
      effectively reveals a map of the association field. These association fields are
      not greatly affected by contrast, and can be demonstrated between contours that
      are presented to separate hemispheres.

PMID- 16289207
TI  - Neuroimaging the retina.

PMID- 16289205
TI  - Effect of mechanical stress on biofilms challenged by different chemicals.
AB  - In this study a methodology was applied in order to ascertain the mechanical
      stability of biofilms, by using a stainless-steel (SS) rotating device immersed
      in a biological reactor where biofilms formed by Pseudomonas fluorescens were
      allowed to grow for 7 days at a Reynolds number of agitation of 2400. The
      biofilms developed with this system were characterised in terms of amount of
      total, extracellular and intracellular proteins and polysaccharides, amount of
      mass, metabolic activity and mechanical stability, showing that the biofilms were
      active, had a high content of extracellular constituents and an inherent
      mechanical stability. In order to assess the role of chemical agents on the
      mechanical stability, the biofilms were exposed to chemical agents followed by
      mechanical treatments by submission to increase Reynolds number of agitation.
      Seven different chemical agents were tested (two non-oxidising biocides, three
      surfactants and two oxidising biocides) and their effects on the biofilm
      mechanical stability were evaluated. The increase in the Reynolds number
      increased the biofilm removal, but total biofilm removal was not found for all
      the conditions tested. For the experiment without chemical addition (only
      mechanical treatment), the biofilm remaining on the surface was about 76%. The
      chemical treatment followed by the subsequent mechanical treatment did not remove
      all the biofilms from the surface. The biofilm remaining on the SS cylinder
      ranged from 3% to 62%, depending on the chemical treatment, showing that the
      chemical treatment is far from being a cause that induces massive biofilm
      detachment and even the synergistic chemical and mechanical treatments did not
      promote biofilm removal. Some chemical agents promoted an increase in the biofilm
      mechanical stability such as glutaraldehyde (GTA), benzalkonium chloride (BC),
      except for the lower concentration tested, and sodium dodecyl sulphate (SDS),
      except for the higher concentration tested. Treatments that promoted biofilm
      removal, to an extent similar to the control experiment (without chemical
      treatment), were BC, for the lower and the higher concentration of SDS.
      Cetyltrimethyl ammonium bromide (CTAB), ortho-phthalaldehyde (OPA), sodium
      hydroxide (NaOH) and sodium hypochlorite (SHC) promoted the weakening of the
      biofilm mechanical stability.

PMID- 16289208
TI  - Visual discrimination of local surface structure: slant, tilt, and curvedness.
AB  - In four experiments, observers were required to discriminate interval or ordinal
      differences in slant, tilt, or curvedness between designated probe points on
      randomly shaped curved surfaces defined by shading, texture, and binocular
      disparity. The results reveal that discrimination thresholds for judgments of
      slant or tilt typically range between 4 degrees and 10 degrees; that judgments of
      one component are unaffected by simultaneous variations in the other; and that
      the individual thresholds for either the slant or tilt components of orientation
      are approximately equal to those obtained for judgments of the total orientation
      difference between two probed regions. Performance was much worse, however, for
      judgments of curvedness, and these judgments were significantly impaired when
      there were simultaneous variations in the shape index parameter of curvature.

PMID- 16289209
TI  - The non-monophyletic origin of the tRNA molecule and the origin of genes only
      after the evolutionary stage of the last universal common ancestor (LUCA).
AB  - A model has been proposed suggesting that the tRNA molecule must have originated
      by direct duplication of an RNA hairpin structure [Di Giulio, M., 1992. On the
      origin of the transfer RNA molecule. J. Theor. Biol. 159, 199-214]. A non
      monophyletic origin of this molecule has also been theorized [Di Giulio, M.,
      1999. The non-monophyletic origin of tRNA molecule. J. Theor. Biol. 197, 403
      414]. In other words, the tRNA genes evolved only after the evolutionary stage of
      the last universal common ancestor (LUCA) through the assembly of two minigenes
      codifying for different RNA hairpin structures, which is what the exon theory of
      genes suggests when it is applied to the model of tRNA origin. Recent
      observations strongly corroborate this theorization because it has been found
      that some tRNA genes are completely separate in two minigenes codifying for the
      5' and 3' halves of this molecule [Randau, L., et al., 2005a. Nanoarchaeum
      equitans creates functional tRNAs from separate genes for their 5'- and 3'
      halves. Nature 433, 537-541]. In this paper it is shown that these tRNA genes
      codifying for the 5' and 3' halves of this molecule are the ancestral form from
      which the tRNA genes continuously codifying for the complete tRNA molecule are
      thought to have evolved. This, together with the very existence of completely
      separate tRNA genes codifying for their 5' and 3' halves, proves a non
      monophyletic origin for tRNA genes, as a monophyletic origin would exclude the
      existence of these genes which have, on the contrary, been observed. Here the
      polyphyletic origin of genes codifying for proteins is also suggested and
      discussed. Moreover, a hypothesis is advanced to suggest that the LUCA might have
      had a fragmented genome made up of RNA and the possibility that 'Paleokaryotes'
      may exist is outlined. Finally, the characteristic of the indivisibility of
      homology that these polyphyletic origins seem to remove at the sequence level is
      discussed.

PMID- 16289210
TI  - Theoretical framework for octopus rhodopsin crystallization.
AB  - Bacteriorhodopsin (bR) is presently a classical example of membrane protein
      crystallization. We are comparing the structure of bR with the homology model of
      octopus rhodopsin (octR), which is similar in topology to bR and as highly
      ordered in its native membranes as bR in purple membranes. Such comparison
      provides insights for optimization of present octR experimentation both for
      crystallization and for application in nanobiotechnology in a manner similar to
      bR, and possibly even superior in optical computation.

PMID- 16289211
TI  - Chemical composition and hygroscopic properties of size-segregated aerosol
      particles collected at the Adriatic coast of Slovenia.
AB  - The chemical composition as well as the water uptake characteristics of aerosols
      was determined in size-segregated samples collected during November 2002 on the
      Slovenian coast. Major ions, water-soluble organic compounds (WSOC), short-chain
      carboxylic acids and trace elements were determined in the water-soluble fraction
      of the aerosol. Total aerosol black carbon (BC) was measured from filter samples.
      Our results showed that the origin of air masses is an important factor that
      controls the variation in the size distribution of the main components. Very high
      concentrations of WSOC as well as higher concentrations of BC were found under
      mostly continental influence. Besides the main ionic species (SO4(2-), NH4(+),
      K+) in the finest size fraction (0.17-0.53 microm), the concentration of NO3(-)
      was also high. The difference between the two different air mass origins is
      particularly expressed for Cl-, Na+, Mg2+ and Ca2+ determined in particles larger
      than 1.6 microm. As expected, a very good correlation was found between Na+ and
      Cl-. A good correlation was found between sea salt elements and elements of
      crustal origin (Na+, Cl-, Mg2+, Ca2+, Sr). A good relationship between typical
      anthropogenic tracers (K, V and Pb) was also observed. The mass growth factors,
      for all size fractions of aerosols collected under continental influence were
      very low (maximum 2.23 at 94%, 1.6-5.1 microm), while under marine influence the
      mass growth factors increased significantly with the particle size. At 97%
      humidity, the mass growth factors were 6.95 for the size fraction 0.53-1.6 microm
      and 9.78 for larger particles (1.6-5.1 microm).

PMID- 16289212
TI  - Degradation and decolorization of a biodegradable-resistant polymeric dye by
      chelator-mediated Fenton reactions.
AB  - Chelator-mediated Fenton reactions (CMFRs) were used to decolorize a
      biodegradable-resistant polymeric dye (Poly R-478). Screening of different iron
      chelators was performed on Fe(3+)-reduction activity. All chelators showed Fe(3+)
      reduction activity over a wide range of pH (2-7) and each mol of catecholate
      chelators (3,4-dihydroxiphenilacetic acid--DOPAC and 2,3-dihydroxibenzoic acid-
      DHBA) reduced about 5-6 moles of Fe(3+) whereas hydroxamate chelators
      (acetohydroxamic acid-AHA and desferrioxamine B-DFB) reduced Fe(3+)
      stoichiometrically. The most effective decolorization of Poly R-478 was achieved
      by CMFR using catecholate chelators. In addition, a 2(4) factorial design was
      performed with the aim of evaluating the effects of the variables considered in
      this study (pH, [DOPAC], [Fe(3+)] and [H(2)O(2)]) and optimizing the dye
      decolorization, using response surface methodology. Statistical analysis of
      results showed that, in the range studied, except for Fe(3+), all variables have
      a significant effect on dye decolorization. A second-order model is proposed to
      represent the Poly R-478 decolorization. At optimum conditions, complete
      decolorization of the dye (degradation of the chromophoric group) and also
      complete chemical degradation of the dye was observed.

PMID- 16289213
TI  - Comparison of advanced oxidation processes and identification of monuron
      photodegradation products in aqueous solution.
AB  - The photodegradation of monuron (3-(4-chlorophenyl)-1,1-dimethylurea) in aqueous
      solutions under simulated solar irradiation has been conducted by different
      advanced oxidation processes (UV/H(2)O(2), UV/H(2)O(2)/Fe(2+),
      UV/H(2)O(2)/TiO(2), UV/TiO(2), dark H(2)O(2)/Fe(3+)). The degradation rates were
      always higher for the homogeneous catalysis in photo-Fenton reactions
      (UV/H(2)O(2)/Fe(2+)) compared to the heterogeneous photocatalytic systems
      (TiO(2)/UV and UV/H(2)O(2)/TiO(2)). Optimal concentrations of Fe(2+) and H(2)O(2)
      for the abatement of the herbicide in the photo-Fenton system were found to be 1
      mM Fe(II) and 10 mM H(2)O(2). Several intermediary products were identified using
      large volume injection micro-liquid chromatography with UV detection (mu-LC-UV),
      mu-LC-MS and GC-MS techniques and a degradation mechanism has been proposed.

PMID- 16289214
TI  - Photocatalytic hydrogen generation in the presence of chloroacetic acids over
      Pt/TiO2.
AB  - In the presence of chloroacetic acids, the photocatalytic hydrogen evolution and
      decomposition of the pollutants over Pt/TiO2 have been investigated. The Pt/TiO2
      was prepared by photodeposition. Monochloroacetic acid and dichloroacetic acid
      enhance photocatalytic hydrogen generation, whereas trichloroacetic acid does
      not. The photocatalytic oxidation of monochloroacetic acid and dichloroacetic
      acid mainly produces CO2, HCl and formaldehyde, whereas the photocatalytic
      oxidation of trichloroacetic acid mainly produces CO2 and HCl. The effect of the
      concentration of monochloroacetic acid and dichloroacetic acid on the hydrogen
      generation rate is consistent with a Langmuir-Hinshelwood kinetic model. A
      possible reaction mechanism was discussed.

PMID- 16289216
TI  - PCDD/DF in leachates from Korean MSW landfills.
AB  - We analyzed levels of PCDD/DF in leachate liquid and solid from five Korean
      municipal solid waste landfills to investigate the relationship between PCDD/DF
      and dissolved organic carbon and suspended solids in raw leachate. The
      concentrations of PCDD/DF ranged from 173.2 to 1329.4 pg/l and 4.1 to 46.22 pg
      TEQ/l. The range of PCDD/DF was 123.2-1161.3 pg/l in leachate solid and 50.0
      383.3 pg/l in leachate liquid. Our results indicated that PCDD/DF in solid play a
      major role in determining their concentration levels, and the distribution of
      isomers in solid was almost the same as in liquid leachate. In addition, highly
      chlorinated PCDD/DF, such as HpCDD/DF and OCDD/DF, accounted for more than 70% of
      all isomers. Levels of PCDD/DF in liquid were strongly correlated with dissolved
      organic carbon concentrations, which increase the leachability (R2 = 0.92 in
      Korean leachate) of PCDD/DF from contaminant sources. Despite this high linearity
      between dissolved organic carbon and dissolved PCDD/DF, we observed no strong
      relationship between dissolved organic carbon and solid phase PCDD/DF (R2 =
      0.001). Dissolved organic carbon scarcely affects dissolved PCDD/DF to be
      combined with solids. As a result, it is not appropriate for incinerated ash to
      be dumped with municipal solid wastes, as they have a large potential to result
      in high levels of organic matter, and therefore PCDD/DF, in leachate.

PMID- 16289215
TI  - Photosensitized degradation of bisphenol A involving reactive oxygen species in
      the presence of humic substances.
AB  - The photodegradation of endocrine disrupter bisphenol A (BPA) in the presence of
      natural humic substances (HS) under simulated solar irradiation was studied. BPA
      underwent slow direct photolysis in neutral pure water, but rapid photosensitized
      degradation in four kinds of HS, following pseudo-first-order reaction. Reactive
      oxygen species (ROS) formed from HS were determined, including OH, (1)O(2) and
      H(2)O(2). The enhancement of BPA degradation by adding Fe(III) was primarily
      attributed to the oxidation of OH produced from photo-Fenton-like reaction. And
      the joint effects of HS and nitrate ions coexisting on BPA degradation appeared
      to depend on respective concentration levels. The effects of dissolved oxygen
      suggested that the energy transfer between excited state of SRFA and NOFA likely
      occurred, while the abstraction of phenolic hydrogen atom to reactive triplet
      state of NOHA possibly took place. Based on the structural analyses of main
      intermediates and degradation products of BPA detected by GC-MS, the possible
      photodegradation pathways were proposed, involving the alky cleavage, alkyl
      oxidation and OH addition. This study gave a better understanding for the
      photochemical transformation of BPA induced by ROS generated from natural water
      composition under sunlight irradiation.

PMID- 16289217
TI  - Trace elements and butyltins in a Dall's porpoise (Phocoenoides dalli) from the
      Sanriku coast of Japan.
AB  - Concentrations and body burdens of 14 trace elements (Hg, Cr, Mn, Co, Cu, Zn, Sr,
      Ag, Cd, V, Se, Pb, Mo, and Fe) and butyltins (BTs) (tributyltin TBT, dibutyltin
      DBT, and monobutyltin MBT) were determined in various tissues of a mature male
      Dall's porpoise (Phocoenoides dalli) collected off the Sanriku coast of Japan.
      Selective accumulation in this porpoise was observed for Hg, Mn, Cu, Ag, Mo, Fe,
      and total BTs (TBT, DBT, and MBT) in the liver, Cd in the kidney, Zn, Sr, V, Pb,
      and Co in the bone, and Se in the skin. In contrast, Cr concentrations in all
      tissues were similar. This distribution pattern in this mature porpoise was in
      general agreement with the accumulation characteristics of trace elements and
      butyltins reported for other marine mammals. The whole body of the porpoise
      contained approximately 62 g Fe, 8.8 g Zn, 4.0 g Sr, 0.6g Se, 0.41 g Cu, 0.19 g
      Hg, 0.17 g Cd, 0.16 g Mn, 0.05 g Cr, 0.009 g Ag, 0.008 g Mo, 0.005 g Pb, 0.004 g
      Co, and 0.7 mg of BTs (0.4 mg TBT, 0.2 mg DBT, and 0.1 mg MBT). Metabolism of TBT
      to its breakdown products of this porpoise seems to be limited, since TBT still
      accounted for about half of the total burden of BTs. As in the cases of Hg, Mn,
      Cu, Se, and Fe, the muscle was the most important reservoir (43%) for the whole
      body burden of total BTs, 80% of which was TBT, and thus muscle played a crucial
      role in the higher body composition of TBT in this Dall's porpoise.

PMID- 16289218
TI  - Measuring bioavailability of polychlorinated biphenyls in soil to earthworms
      using selective supercritical fluid extraction.
AB  - If the release mechanisms during selective chemical extraction of persistent
      organic pollutants (POP) mimic release mechanisms in natural systems during
      biological uptake, then a selective non-exhaustive extraction could give a
      quantitative measure of the bioavailable POP fraction. Supercritical fluid
      extraction (SFE) is suggested as a possible technique to estimate the amount of
      bioavailable polychlorinated biphenyls (PCBs) at contaminated sites and hence
      serve as a new tool in risk assessment. The uptake of PCBs by earthworm (Eisenia
      foetida) was investigated. PCB contaminated soil was pre-extracted with selective
      non-exhaustive SFE (50 degrees C, 350 bar, 1h), which removed on average 70% of
      the individual PCBs. Earthworms were placed in this pre-extracted soil, as well
      as in untreated soil. After 10 days, the PCB uptake by earthworms in the two
      systems was compared. The bioaccumulation factor (BAF) was 83% lower in the pre
      extracted system than in the untreated system, demonstrating that SFE extracts
      primarily bioavailable contaminants. From the data, the bioavailable fraction
      could also be calculated to be 75%, which is very close to the 70% removed by SFE
      under the applied conditions. This suggests that the chemical methodology is
      capable of measuring the bioavailable fraction very accurately in this system.

PMID- 16289219
TI  - Removal of nanoparticles from CMP wastewater by magnetic seeding aggregation.
AB  - CMP wastewaters have high solids content resulted from abrasive nanoparticles.
      Tremendous amount of ultrapure water consumption also makes the removal of
      nanoparticles from CMP wastewaters an important issue. Magnetic seeding
      aggregation of silica nanoparticles from the oxide CMP wastewater is studied in
      this work. Magnetite nanoparticles were synthesized and used as seeding
      particles. The turbidity of the CMP wastewater was reduced from 110 NTU to 7 NTU
      when solution pH was 6 and no addition of salt. This is because silica and
      magnetite nanoparticles were highly oppositely charged and the aggregation
      between silica and magnetite nanoparticles was achieved by electrostatic
      attractions. When the seeded wastewater was placed in a magnetic field strength
      higher than 800 G, the turbidity of the CMP wastewater was reduced to 1 NTU,
      which was clearer than the CMP wastewater treated by many other technologies.

PMID- 16289220
TI  - Photocatalytic demethylation of 2,4,6-trinitrotoluene (TNT) by porphyrins.
AB  - Illumination of tetraphenyl porphyrin sulfonate (TPPS), CuTPPs and FeTTPPS in
      solution with trinitrotoluene (TNT) at pH7 at room temperature using tungsten
      lamp illumination results in the degradation of TNT to yield trinitrobenzoic acid
      and trinitrobenzene. No other degradation products are observed. The rate of TNT
      degradation follows the series TPPS > FeTPPS > CuTPPS.

PMID- 16289221
TI  - Phytotreatment of propellant contamination.
AB  - Nitroglycerine (NG) and 2,4-dinitrotoluene (2,4-DNT) are propellants often found
      in soil and groundwater at military firing ranges. Because of the need for
      training with live ammunition, control or cleanup of these contaminants may be
      necessary for the continued use of these firing ranges. One inexpensive approach
      for managing sites exposed to these contaminants is the use phytoremedation,
      particularly using common or native grasses. In this study, the uptake of NG and
      2,4-DNT from water by three common grasses, yellow nutsedge (Cyperus escalantus),
      yellow foxtail (Setaria glauca), and common rush (Juncus effusus), was
      investigated using hydroponic reactors. Rapid removal from solution by all
      grasses was observed, with yellow nutsedge removal rates being the highest. NG or
      2,4-DNT accumulated in the tissues in all of the plants, except yellow foxtail
      did not accumulate NG. Higher concentrations were observed in killed roots,
      demonstrating the presence of plant-based enzymes actively transforming the
      contaminants. Yellow nutsedge was also grown in 2,4-DNT spiked soil. Significant
      uptake into the plants roots and leaves was observed and concentrations in the
      soil decreased rapidly, although 2,4-DNT concentration also decreased in the
      unplanted controls. In summary, the three grasses tested appear to be good
      candidates for phytoremediation of propellant contamination.

PMID- 16289222
TI  - Analysis of regional and temporal characteristics of PM10 during an Asian dust
      episode in Korea.
AB  - This study analyzes the regional and temporal distributions of PM10
      concentrations observed in major metropolitan cities in Korea before, during and
      after a recent Asian dust episode in 2002. There were spatial and temporal
      variations in PM10 concentrations among the mid-western, the southwestern, the
      southeastern, and the southern parts of Korea during this Asian dust period due
      to the different air mass movement time and the different wind directions and
      speeds of prevailing winds in each city or region. The origins of the three-day
      Asian dust episode were identified by an analysis of two-day backward isentropic
      air trajectories. The different origins for each day also significantly
      contributed to the spatial and temporal variations in PM10 concentrations. A
      significant relationship was found between PM10 concentrations on the day
      preceding the first peak day and the first peak day of the Asian dust period but
      only in the mid-western areas. The concentrations of PM10 just after the Asian
      dust episode were much higher than those just before. There was a significant
      increase in a coarse fraction, having soil origins, of particles during the Asian
      dust episode. Concentrations of Mn, Fe, Ni and Cr extracted from the total
      suspended particulate (TSP) samples collected in 7 cities during the Asian dust
      episode were much higher when compared with other days in 2001. However, the
      Asian dust did not consistently increase the concentrations of lead, cadmium and
      copper as they are influenced by local sources such as local traffic or
      industrial emissions.

PMID- 16289223
TI  - Macrophyte growth in a pilot-scale constructed wetland for industrial wastewater
      treatment.
AB  - A pilot-scale wetland was constructed to assess the feasibility of treating the
      wastewater from a tool industry in Santo Tome, Santa Fe, Argentina. The
      wastewater had high conductivity and pH, and contained Cr, Ni and Zn. This paper
      describes the growth of vegetation in the experimental wetland and the nutrient
      and metal removal. The wetland was 6 x 3 x 0.4 m. Water discharge was 1000 l d(
      1) and residence time was 7d. After the wetland was rendered impermeable,
      macrophytes from Middle Parana River floodplain were transplanted. Influent and
      effluent quality was analyzed every 15 d. TP, Cr, Ni and Zn concentrations in
      leaves, roots and sediment (inlet and outlet) were measured monthly. Cover and
      biomass of predominant species were estimated. Also, greenhouse experiments were
      carried out to measure the effects of conductivity and pH on floating species.
      The variables measured in the influent were significantly higher than those in
      the effluent, except for HCO(3)(-) and NH(4)(+). TP and metal concentrations in
      sediment at the inlet were significantly higher than those at the outlet.
      Conductivity and pH of the incoming wastewater were toxic for the floating
      species. Typha domingensis displaced the other species and reached positive
      relative cover rate and biomass greater than those at the undisturbed natural
      environment. T. domingensis proved to be highly efficient for the treatment of
      wastewater. For that reason, it is the advisable species for the treatment of
      wastewater of high conductivity and pH enriched with metals, characteristic of
      many industrial processes.

PMID- 16289224
TI  - Response of submerged plant (Vallisneria spinulosa) clones to lead stress in the
      heterogenous soil.
AB  - In order to evaluate risk spreading among clones and antioxidant defence response
      of clonal ramets, turions of Vallisneria spinulosa, the dominant clonal plant of
      the submerged plant community in most of the lakes in Middle and Lower Reaches of
      Yangtze Rive, China, were planted in the heterogeneous soils contaminated with 40
      and 160 microg g(-1) Pb (dry weight) in a greenhouse. After 100 d, the ranking
      order of tissue Pb concentrations in organs of the ortets (parental plants) was
      root>turion>rhizome>leaf, but that of tissue Pb quantities was
      leaf>turion>rhizome>root, due to their different biomass. Some of Pb was
      transferred from the ortets exposed in the Pb-supplied soil to leaves of the
      offspring growing in the favorable patch through rhizome (connective organ). A
      high foliar Pb concentration induced a significant decrease in superoxide
      dismutases, peroxidase and catalase activities. Catalase was more sensitive to Pb
      than the other two antioxidant enzymes. However, a low foliar Pb concentration,
      in the ortets exposed to 40 microg g(-1) Pb and in all of the offspring, slightly
      increased the activities of superoxide dismutases and peroxidase. The biomass
      accumulation per ortet and the biomasses percentages allocation to the roots and
      the leaves in Pb treatments decreased markedly. Nevertheless, there was no
      significant difference in biomass accumulation of the offspring between the low
      Pb level treatment and the control. The biomass percentage allocated to the root
      of the offspring was found to be larger than that of the ortets.

PMID- 16289225
TI  - Effect of earthworms (Eisenia fetida) on the fractionation and bioavailability of
      rare earth elements in nine Chinese soils.
AB  - The effect of earthworm (Eisenia fetida) activity on soil pH, dissolved organic
      carbon (DOC), fraction distribution pattern and bioavailability of rare earth
      elements (REEs) Y, La, Ce, Pr and Nd in nine Chinese soils were investigated
      using pot experiments. A three-step extraction procedure recommended by the
      European Community (Standards, Measurements and Testing Programme) was used to
      fractionate REEs in soils into water soluble, exchangeable and carbonate bound
      (B1), Fe- and Mn-oxides bound (B2) and organic matter and sulfide bound (B3).
      Inoculated with earthworms, the soil pH, DOC and water-soluble rare earth
      elements fraction increased. A significant correlation was obtained between the
      increased DOC and the increased water-soluble REEs. REEs in fraction B1 increased
      after earthworm inoculation, while those in fraction B3 decreased. No significant
      differences were observed for REEs in fraction B2. The biomass and the
      concentrations of REEs in wheat shoots and roots increased after the treatment
      with earthworms. The results demonstrated that earthworm activity increased the
      mobility and bioavailability of REEs in soils.

PMID- 16289226
TI  - Polychlorinated biphenyls, sex steroid hormones and liver retinoids in adult male
      European common frogs Rana temporaria.
AB  - Declines in amphibian populations and species biodiversity during the last
      decades has called for an assessment of possible threats to these animals.
      Polychlorinated biphenyls (PCBs) are known endocrine disrupting contaminants and
      are found in high levels in some populations of wild living amphibians. To
      evaluate the endocrine disrupting potential of PCBs in adult frogs, Aroclor 1,254
      were subcutaneously injected into male European common frogs Rana temporaria. The
      injected doses ranged from 0.01 to 100 mg/kg body mass, resulting in liver
      concentrations between 74 and 133,619 microg/kg ww. After 14 days, serum
      testosterone (T), estradiol (E) and hepatic retinol (R) and retinylpalmitate (RP)
      were easured. No dose dependent effects were found on levels of hormones or
      retinoids. However, a significantly higher within-group variation in the E-T
      ratio in the exposed groups may indicate that the sex-hormone homeostasis of male
      R. temporaria is affected by PCBs shortly after arousal from hibernation, but
      that the effects are subtle and that several different mechanisms are involved.
      The lack of direct effect on T, E, R and RP may be due to the timing of exposure
      (shortly after arousal from hibernation), or due to a relatively short exposure
      time to Aroclor 1,254. Based on the results, we propose that future research
      should focus on effects of PCBs in relation to the different physiological phases
      frogs experience throughout the year (hibernation, reproduction etc.).

PMID- 16289227
TI  - Calculation of environmental concentration and comparison of output for existing
      chemicals using regional multimedia modeling.
AB  - The environmental fate of 40 existing chemicals is discussed using the EUSES
      multimedia distribution and risk assessment model with site-specific parameter
      setting in an urban area of Japan including a highly industrial region. There has
      been a strong need to assess the environmental fate of a huge number of existing
      chemicals. Data on the emission amounts of chemicals are essential for such
      prediction, and PRTR surveys may yield this data. The study delivered the
      following results: (1) Volatile compounds with large amounts of emission showed
      higher predicted concentrations in air, and the concentrations of several
      compounds agreed well with averaged monitoring data within an order of magnitude.
      (2) A close relationship was found between the concentration of water and that of
      sediment, suggesting that the fate of chemicals in sediment essentially depended
      on the water environment. (3) A group of volatile solvents had high mass
      distribution ratio to air. Some compounds having high solubility in water were
      also included in that group due to the high ratio of air emission. Highly
      hydrophobic compounds with logK(OW) larger than 6.0 showed a high distribution
      ratio to soil and sediment. (4) Volatile compounds were mostly taken through air.
      The exposure through fish is a dominant pathway for highly hydrophobic compounds.
      (5) Exposure ratio could be gathered from physicochemical properties. The
      exposure from fish intake was roughly estimated by logK(OW), whereas exposure
      from air and water intake was difficult to estimate simply by vapor pressure and
      solubility in water, respectively.

PMID- 16289228
TI  - Thermodynamics of metal cation binding by a solid soil-derived humic acid:
      binding of Fe(III), Pb(II), and Cu(II).
AB  - Metal binding and release by solid humic acids (HAs) in soils and sediments can
      affect metal mobility and bioavailability. Isotherms for tight binding of
      Fe(III), Pb(II) and Cu(II) by a solid humic acid at pH2.0 fit the Langmuir
      binding model. Low pH was chosen to protonate the HA carboxylate groups and avoid
      metal cation hydrolysis. Binding of Fe(III), Pb(II) and Cu(II) occurs in one
      detectable step labeled A. Site capacities nu(A) are temperature-independent from
      10.0 to 40.0 degrees C and point to binding by charge-neutralization to form
      solid complexes M(OOC-R)(n)(s), where n appears to be 2 for Pb(II) and 3 for
      Fe(III). Thermodynamic data pairs (DeltaH(A), DeltaS(A)) for metal binding are
      linearly correlated with previous data for Ca(II), Co(II) and Mg(II) binding by
      solid HAs.

PMID- 16289229
TI  - Effects of riboflavin on the phototransformation of benzo[a]pyrene.
AB  - Riboflavin (Vitamin B2) is a natural dye-sensitizer habitually present in natural
      waters. Effects of riboflavin as photosensitizer on the transformation of
      benzo[a]pyrene (BaP) (10 microM) in the aqueous-organic solvent
      (water/acetonitrile/methanol 50/40/10) were investigated in this study. The
      photolysis half life of BaP in solution containing 50 microM riboflavin was 5
      min, compared to 98 min in the absence of riboflavin. The rate of
      phototransformation of BaP increased as the concentration of riboflavin was
      raised from 10 microM to 100 microM under both natural sunlight and UVA
      irradiation. The half life of BaP in the presence of 50 microM riboflavin was
      10.6 min and 43.1 min when exposed to visible range of natural sunlight and UVA
      irradiation respectively. Riboflavin decomposes under natural sunlight.
      Lumichrome, a principal photoproduct of riboflavin, was shown to photosensitize
      BaP under natural sunlight after photolysis of riboflavin. Our study indicated
      that other photoproducts from riboflavin, such as lumiflavin, were also involved
      in the phototransformation of BaP under sunlight when riboflavin diminished. The
      major photoproducts in the photolysis of BaP were identified as 1,6
      benzo[a]pyrene-dione, 3,6-benzo[a]pyrene-dione, 6,12-benzo[a]pyrene-dione by
      using high performance liquid chromatography (HPLC). All these products were
      detected in the samples which were irradiated under different light sources and
      in the presence or absence of riboflavin. The possible phototransformation
      mechanism was discussed.

PMID- 16289231
TI  - Degradation of lansoprazole and omeprazole in the aquatic environment.
AB  - Lansoprazole and omeprazole degrade in water leading to sulfides,
      benzimidazolones and a red complex material. Degradation is accelerated in acid
      medium and by solar simulator irradiation. Benzimidazoles, dianilines and
      pyridines have also been identified.

PMID- 16289230
TI  - Genetic differences in the production of male neonates in Daphnia magna exposed
      to juvenile hormone analogs.
AB  - We studied the susceptibility of three genetically different strains of the
      cyclical parthenogen Daphnia magna (Cladocera, Crustacea) in producing male
      neonates following exposure to juvenile hormone analogs. In experiment 1, NIES,
      Clone A, and Belgium A strains were exposed to the insect growth regulators
      (IGRs) fenoxycarb or epofenonane in a 21-day reproduction experiment. Fenoxycarb
      exposure decreased the total number of neonates and increased production of male
      neonates in a concentration-dependent manner in the NIES strain. The decrease in
      the total number of neonates was so great in Clone A following fenoxycarb
      exposure that male neonates were not observed, even at the highest concentration,
      where the total number of neonates was only 2% of the control. In the Belgium A
      strain, male neonates were observed at a rate of about 20% following exposure to
      the highest fenoxycarb concentration, but the total number observed was small.
      Epofenonane did not decrease reproduction in the NIES and Belgium A strains as
      dramatically as did fenoxycarb, but the neonatal sex ratio changed in a
      concentration-dependent manner. Although the ratio of males was as low as about
      10%, induction of male neonates was also observed in Clone A following
      epofenonane exposure. In experiment 2, gravid females were exposed to high
      concentrations (5 or 10 microg/l) of fenoxycarb or pyriproxyfen for 12h. These
      treatments induced the production of male neonates in all strains, with a small
      decrease in the total number of neonates. Although induction of male neonates by
      juvenile hormones and their analogs was universal among genetically different
      strains, care is needed in interpreting the results of the 21-day reproduction
      tests, because decreased numbers of neonates at higher concentrations could
      obscure the presence of male neonates.

PMID- 16289232
TI  - Chiral signatures of PCB#s 95 and 149 in indoor air, grass, duplicate diets and
      human faeces.
AB  - Chiral signatures of PCB#s 95 and 149 are reported for indoor air, grass,
      omnivorous and vegan duplicate human diet homogenates, and human faeces.
      Comparison of chiral signatures of both congeners in grass with those reported
      previously for outdoor air (measured at a height of 1.5 m) and soil at the same
      location suggest that volatilisation of PCBs present in soil may exert a
      significant influence on concentrations in grass. Duplicate diet homogenates
      display racemic signatures for both congeners. Alongside the racemic signatures
      in both outdoor and indoor air, this implies that human intake via diet and
      inhalation is racemic, and that the previously observed variation between
      individuals in the extent of enantioselective degradation in human liver samples
      indicates possible inter-individual variation in ability to metabolise PCBs.
      Chiral signatures of PCB# 95 in the 10 human faecal samples analysed indicate 8
      to be racemic, but 2 to display an excess of the 2nd eluting enantiomer. This is
      consistent with the excess of the 1st eluting enantiomer reported elsewhere for
      human liver samples, as it implies enantioselective excretion of the 2nd eluting
      enantiomer. However, the racemic residues for PCB# 95 in the majority of faecal
      samples are a possible indication that enantioselective interaction of chiral
      PCBs with cytochrome P450 occurs slowly. The racemic or near-racemic signatures
      observed for PCB# 95 and 149 in indoor air match closely those in outdoor air,
      but differ from those in soil, adding to the weight of evidence that ventilation
      of indoor air is a far more significant contributor to outdoor air concentrations
      than volatilisation of PCBs from soil.

PMID- 16289233
TI  - Submarine tailings placement by a copper mine in the deep anoxic zone of the
      Black Sea.
AB  - Copper mine tailings are discharged to the anoxic zone of the Black Sea at 350 m
      depth, and there is currently consideration of reducing this discharge depth.
      Oceanographic sampling has provided data allowing calculating whether dilute
      buoyant plumes will separate from the tailings density current as predicted.
      Calculations for various discharge rates and slurry dilutions indicate that such
      plumes will rise approximately 89 m above the discharge depth, hence will remain
      in the deep anoxic zone below the permanent pycnocline at approximately 150 m
      depth at both the present and currently proposed sites. There is some indication
      from relative seawater density measures that these plumes will drift rather than
      spreading diffusely. Plume separation from controlled discharges of the tailings
      slurry was confirmed by visual observations in an experimental tank. The
      oceanographic sampling also showed that trace element levels in the seawater by
      the discharge point remained below Turkish marine receiving water quality
      criteria.

PMID- 16289235
TI  - Effects of ingested fruiting bodies, submerged culture biomass, and acidic
      polysaccharide glucuronoxylomannan of Tremella mesenterica Retz.:Fr. on glycemic
      responses in normal and diabetic rats.
AB  - Mushroom polysaccharides have been shown to regulate glucose metabolism. Using
      male Wistar rats injected with saline (normal rats), streptozotocin (STZ-NT
      rats), or streptozotocin plus nicotinamide (STZ+NT rats), we investigated the
      hypoglycemic activity of orally ingested fruiting bodies (FB), submerged culture
      biomass (CM), or the acidic polysaccharide glucuronoxylomannan (GXM) of Tremella
      mesenterica, an edible jelly mushroom. Our results demonstrated that FB ingestion
      significantly attenuated the elevated blood glucose levels in an oral glucose
      tolerance test (OGTT) in STZ-NT rats. However, in STZ+NT rats, FB, CM, and GXM
      ingestion significantly attenuated the increases in food and water intake, 2-h
      postprandial blood glucose concentrations, and blood glucose levels in OGTT.
      Moreover, FB and GXM ingestion significantly decreased serum concentration of
      fructosamine in STZ+NT rats. Our results indicated that T. mesenterica might be
      developed as a potential oral hypoglycemic agent or functional food for diabetic
      patients and for persons with high risk for diabetes mellitus.

PMID- 16289234
TI  - Characterization of nitrogen-fixing cyanobacteria in the Brazilian Amazon
      floodplain.
AB  - The diversity of the free-living nitrogen-fixing cyanobacterial community in the
      floodplain sediments along the Solimoes and Amazon Rivers and some of their
      tributaries (Japura, Negro and Madeira) was investigated. Five cyanobacterial
      genera were morphologically identified, four of which (Nostoc, Calothrix,
      Cylindrospermum and Fischerella) have not previously been isolated from the
      Brazilian Amazon floodplain. Nostoc strains were the most commonly found
      heterocyst-forming cyanobacteria. Five strains (N. muscorum CENA18 and CENA61, N.
      piscinale CENA21, Cylindrospermum sp. CENA33 and Fischerella sp. CENA19) were
      selected for growth measurement, ability to fix N2 and phylogenetic analysis,
      based on their widespread distribution and morphological distinction. Molecular
      analyses employing 16S rRNA sequences indicated that some of the isolates may
      represent novel cyanobacterial species. Dinitrogen fixed by these strains was
      measured indirectly as acetylene reduction activity and ranged from 11.5 to 22.2
      nmol C2H4 microg Chl a(-1) h(-1). These results provide evidence of widespread
      and importance of nitrogen-fixing cyanobacteria as a source of N inputs in the
      Amazonian ecosystem.

PMID- 16289236
TI  - Connexin 32 down-regulates the fibrinolytic factors in metastatic renal cell
      carcinoma cells.
AB  - Fibrinolytic factors have an important role in tumor progression through the
      degradation of extracellular matrix. The increased levels of urokinase-type
      plasminogen activator (uPA), uPA-receptor (uPAR) and type-1 PA inhibitor (PAI-1)
      are reported in human renal cell carcinoma (RCC). Connexin (Cx) gene, a member of
      gap junction, is known to act as a tumor suppressor gene. We have reported that
      Cx32 improves malignant phenotypes of metastatic RCC cells via the inhibition of
      Src-dependent signaling. In this study, we examined the effect of expression of
      Cx32 gene on the production of uPA, uPAR and PAI-1, and on the induction of PAI-1
      stimulated by hypoxia in a human metastatic RCC cell line, Caki-1 cells. Cx32
      expression decreased both mRNA level and production of PAI-1, uPA and uPAR in
      Caki-1 cells. Cx32 also decreased hypoxia-inducible factor (HIF)-1alpha and HIF
      2alpha mRNA level. PP1, a Src inhibitor, significantly decreased PAI-1, uPA, uPAR
      and HIF-alpha mRNA levels in Caki-1 cells. Furthermore, Cx32 suppressed the
      induction of HIF-2alpha protein in Caki-1 cells under hypoxia. PAI-1 mRNA level
      in Cx32-transfected Caki-1 cells was lower than that of mock transfectant under
      hypoxic conditions. These results suggest that Cx32 might reduce PAI-1, uPA and
      uPAR production in metastatic RCC cells via the inhibition of Src-dependent
      induction of HIF-1alpha and HIF-2alpha gene expression and that Cx32 might
      suppress hypoxia-inducible gene expression under hypoxic conditions.

PMID- 16289237
TI  - Effect of social isolation on 24-h pattern of stress hormones and leptin in rats.
AB  - This work analyzes the effect of social isolation of growing male rats on 24-h
      changes of plasma prolactin, growth hormone, ACTH and leptin, and on plasma and
      adrenal corticosterone concentrations. At 35 days of life, rats were either
      individually caged or kept in groups (6-8 animals per cage) under a 12:12 h
      light/dark schedule (lights on at 08:00 h). A significant arrest of body weight
      gain regardless of unchanged daily food intake was found in isolated rats after 2
      weeks of isolation. On the 4th week, rats were killed at 6 time intervals during
      a 24-h cycle, beginning at 09:00 h. In isolated rats the 24-h pattern of all
      parameters tested became distorted, as assessed by Cosinor analysis. When
      analyzed as a main factor in a factorial analysis of variance, isolation
      decreased plasma prolactin and growth hormone, increased plasma leptin and
      corticosterone while decreased adrenal corticosterone. Plasma corticosterone
      levels correlated significantly with plasma ACTH and with adrenal corticosterone
      levels in group-caged rats only. These changes can be attributed to an effect of
      mild stress on the endogenous clock that modulates the circadian hormone release.

PMID- 16289238
TI  - Low-density lipoprotein receptor-related protein 5 variant A1330V is a
      determinant of blood pressure in Japanese males.
AB  - We examined the influence of the A1330V variant in the low-density lipoprotein
      receptor-related protein 5 gene on blood pressure in a large cohort of Japanese
      workers. This study used analysis of covariance in a multivariate general linear
      model to adjust for other potential factors such as age, body mass index, blood
      chemistry and lifestyle. The target subjects were 1440 males and 1169 females
      selected from 3834 male and 2591 female workers in a single company. Hypertension
      was defined as systolic blood pressure >or=140 mm Hg and/or diastolic blood
      pressure >or=90 mm Hg or the use of antihypertensive medications. Genotype
      distributions for A1330V in hypertensive males (AA=139(54.5%), AV=101(39.6%),
      VV=15(5.9%)) and females (AA=48(63.2%), AV=24(31.6%), VV=4(5.3%)) were not
      significantly different from normotensive males (AA=594(50.1%), AV=488(41.2%),
      VV=103(8.7%)) and females (AA=568(52.0%), AV=441(40.3%), VV=84(7.7%)). Allele
      distributions were not significantly different in either sex. In males, analysis
      of covariance showed that the VV genotype was associated with a 2.5 mm Hg lower
      diastolic blood pressure and a 2.3 mm Hg lower mean blood pressure than the AA
      genotype. This study indicates that the 1330V allele is an independent factor for
      lower diastolic and mean blood pressure in Japanese males.

PMID- 16289239
TI  - Natureceuticals (natural products), herbal botanicals, psychoactives,
      hallucinogenics and related products.

PMID- 16289240
TI  - Severe ultrastructural mitochondrial changes in lymphoblasts homozygous for
      Huntington disease mutation.
AB  - Mutated huntingtin is expressed in nervous and non nervous system included
      lymphoblasts. Eneregetic metabolism is impaired in Huntington's disease (HD) and
      other neurodegenerative diseases. Human HD lymphoblasts have provided clear-cut
      data on mitochondnal disruption. Here we report morphological, morphometric and
      membrane potential differences in mitochondria from lymphoblasts obtained from
      patients homozygous and heterozygous for the CAG mutation, and controls.
      Homozygotes, who despite a similar age at onset show a more aggressive phenotype
      than heterozygotes, had giant mitochondria and a reduced membrane potential. We
      argue that early mitochondrial impairment at basal level may affect the severity
      of HD progression in patients.

PMID- 16289242
TI  - Simultaneous removal of organic compounds and heavy metals from soils by
      electrokinetic remediation with a modified cyclodextrin.
AB  - Thousands of sites are contaminated with both heavy metals and organic compounds
      and these sites pose a major threat to public health and the environment.
      Previous studies have shown that electrokinetic remediation has potential to
      remove heavy metals and organic compounds when they exist individually in low
      permeability soils. This paper presents the feasibility of using cyclodextrins in
      electrokinetic remediation for the simultaneous removal of heavy metals and
      polycyclic aromatic hydrocarbons (PAHs) from low permeability soils. Kaolin was
      selected as a model low permeability soil and it was spiked with phenanthrene as
      well as nickel at concentrations of 500 mg kg-1 each to simulate typical mixed
      field contamination. Bench-scale electrokinetic experiments were conducted using
      hydroxypropyl beta-cyclodextrin (HPCD) at low (1%) and high (10%) concentrations
      and using deionized water in control test. A periodic voltage gradient of 2VDC cm
      1 (with 5 d on and 2 d off) was applied to all the tests, and 0.01 M NaOH was
      added during the experiments to maintain neutral pH conditions at anode. In all
      tests, nickel migrated as Ni2+ ions towards the cathode and most of it was
      precipitated as Ni(OH)2 within the soil close to the cathode due to high pH
      condition generated by electrolysis reaction. The solubility of phenanthrene in
      the flushing solution and the amount of electroosmotic flow controlled the
      migration and removal of phenanthrene in all the tests. Even though high flow was
      generated in tests using deionized water and 1% HPCD, migration and removal of
      phenanthrene was low due to low solubility of phenanthrene in these solutions.
      The test with 10% HPCD solution showed higher solubility of phenanthrene which
      caused it migrate towards the cathode, but further migration and removal was
      retarded due to reduced electric current and electroosmotic flow. Approximately
      one pore volume of flushing resulted in approximately 50% removal of phenanthrene
      from the soil near the anode. Sustained higher electroosmotic flow with higher
      concentration cyclodextrin and maintaining low soil pH near cathode should be
      investigated to increase removal efficiency of both phenanthrene and nickel.

PMID- 16289241
TI  - The relationship between persistent organic pollutants in maternal and neonatal
      tissues and immune responses to allergens: A novel exploratory study.
AB  - BACKGROUND: Modern persistent organic pollutants (POPs) contamination are logical
      candidates in the investigation of the, as yet, unexplained association between
      allergic disease and progressive industrialisation. POPs have been detected in
      human cord blood, placental tissues and breast milk, and the reported association
      between cord blood IgE levels and cord/placental POP levels has raised concerns
      about potential immunological effects in early life. METHODS: The initial aim of
      this study was to determine if POPs were detectable in maternal blood, cord
      blood, placental tissues, adipose tissue and breast milk samples from randomly
      selected Western Australian women (n = 31), where allergic disease is epidemic.
      Gas chromatography was used to detect polychlorinated biphenyl compounds [PCBs]
      (as Aroclor 1232, 1254, 1260) and organochlorine (OC) pesticides, including p,p'
      DDT, p,p'-DDE, hexachlorobenzene (HCB), lindane, heptachlor epoxide, dieldrin and
      chlordane. Secondly, we assessed the relationship between POP levels detected in
      vivo and maternal and neonatal responses (cytokine and lymphoproliferation) to
      allergens and mitogens. RESULTS: Low level POP contamination was detected in
      adipose tissue and breast milk (but not in cord blood, maternal blood or
      placental tissues). The most ubiquitous compound found in over 90% of adipose
      tissues samples was a OC metabolite of DDT, p,p'-DDE (median 0.07 mg/kg;
      interquartile range [IQR] 0.05-0.12). However, the majority of other OC compounds
      were not detectable and PCB were not detectable in any samples. The three main
      residues detected in breast milk were p,p'-DDE (0.003 mg/l; 0.001-0.009),
      dieldrin (0.001 mg/l; 0.001-0.046) and HCB (0.001 mg/l; 0.001-0.001). These
      levels are significantly lower than reported over 20 years ago. There were no
      consistent relationships between POP levels in vivo and maternal or infant
      responses, with the exception of a significant inverse association (Spearman rank
      correlation: r = -0.406, p = 0.049) between maternal adipose tissue levels of OC
      p,p'-DDE and maternal T helper cell Type 1 interferon [IFN] gamma to mitogens.
      CONCLUSION: This study provides the first evidence (in Australia) since the early
      1990's that adipose OC levels have continued to fall. The negligible levels in
      this randomly selected group are significantly lower than those previously
      recorded, suggesting that POP contamination (at biologically relevant levels) is
      not likely to be a major contributing factor in the increasing rates of allergy
      in Western Australia. However, the relationship between Th1 immune function and
      OC contamination is consistent with other reports and is worth investigating as a
      relevant factor in populations where OC contamination is greater.

PMID- 16289243
TI  - Fine route for an efficient removal of 2,4-dichlorophenoxyacetic acid (2,4-D) by
      zeolite-supported TiO2.
AB  - Zeolites HY, Hbeta and HZSM-5 with different physico-chemical properties were
      chosen as support for TiO2 to illustrate their adsorption, dispersion and
      electronic structure in photocatalysis. The extent of TiO2 loading was monitored
      by XRD and BET surface area measurements. The adsorption capacity of HY zeolite
      was found to be high and hence chosen for further modification to continue the
      investigation. Photodegradation kinetics were carried out with 2,4
      dichlorophenoxyacetic acid (2,4-D) in aqueous solution. The extent of 2,4-D
      degradation on TiO2/HY loading revealed the importance of adsorption in
      photocatalysis. Mineralisation studies on all three zeolites with 1 wt.% TiO2
      loading demonstrated the good dispersion properties of TiO2/HY. Its
      photocatalytic activity was found to be excellent with formulated 2,4-D.
      Comparison of relative photonic efficiencies demonstrated that supported
      photocatalysts exhibited higher activity than some of the commercial
      photocatalysts. The high activity of supported TiO2 is due to synergistic effects
      of improved adsorption of 2,4-D and efficient delocalisation of photogenerated
      electrons by zeolite support.

PMID- 16289244
TI  - Arsenosugars and other arsenic compounds in littoral zone algae from the Adriatic
      Sea.
AB  - In 10 different marine algae from the littoral zone (found between the highest
      and lowest tide marks on the seashore) arsenic compounds were determined by means
      of a high-performance liquid chromatography (anion and cation exchange)-UV
      photochemical digestion-hydride generation-atomic fluorescence spectrometry (HPLC
      UV-HGAFS) system. Samples (Ceramium sp., Cystoseira barbata, Enteromorpha sp.,
      Fucus virsoides, two different species of Gelidium, Padina pavonica, Polisyphonia
      sp. and Ulva rigida) were collected along the Adriatic Sea coast of Slovenia. The
      total arsenic content of the algal samples, as determined by ICP-MS, ranged from
      1.35 to 28.1 microg g(-1) (fresh weight). In all algae but two, the most abundant
      arsenic species found were arsenosugars with minor amounts of other arsenic
      compounds. Cystoseira barbata and Ceramium sp. contained high amounts of mainly
      inorganic arsenic. A small quantity of arsenobetaine was detected in most of the
      investigated Adriatic algae, which probably originates from mesofauna attached to
      the algae in their natural habitat.

PMID- 16289245
TI  - Changes in oxygen consumption and respiratory enzymes as stress indicators in an
      estuarine edible crab Scylla serrata exposed to naphthalene.
AB  - The sublethal effect of naphthalene was studied on the physiology of a mud crab
      Scylla serrata. The 96 h acute toxicity of naphthalene was determined and found
      to be 28 mg 1(-1) (LC100), 18 mg 1(-1) (LC50), 10 mg 1(-1) (LC0) respectively.
      The 30 days sublethal effect (LC0) 9 mg 1(-1), 8 mg 1(-1), 10 mg 1(-1), of
      naphthalene was investigated in the crab S. serrata with reference to oxygen
      consumption and changes in the activity of respiratory enzymes. The results
      indicated that naphthalene caused disturbance in the normal physiology of the
      crab. The bioaccumulation of naphthalene was also investigated in gills,
      hepatopancreas, haemolymph and ovary. The consumption of oxygen increased in the
      naphthalene medium when compared with that of the crabs exposed to naphthalene
      free medium. A decreased trend in the activity of respiratory enzymes such as
      lactate dehydrogenase (LDH), isocitrate dehydrogenase (ICDH), succinate
      dehydrogenase (SDH), malate dehydrogenase (MDH), alpha-ketoglutarate
      dehydrogenase (alpha-KDH) and glutathione (GSH) were recorded in the
      hepatopancreas, ovary and gills of S. serrata for all the tested concentrations
      of naphthalene and the results were analyzed for their significance.

PMID- 16289246
TI  - Effective uptake of decontaminating agent (citric acid) from aqueous solution by
      mesoporous and microporous materials: an adsorption process.
AB  - The presence of citric acid in decontamination waste can cause complexation of
      the radioactive cations resulting in interferences in their removal by various
      treatment processes such as chemical precipitation, ion-exchange, etc., which are
      employed for the removal of radioactivity and may cause potential danger to the
      environment. Mesoporous Al-MCM-41 (Si/Al=30, 51, 72 and 97) and Si-MCM-41
      molecular sieves were synthesized hydrothermally and characterized by XRD, BET
      (surface area) and FT-IR to evaluate the removal of citric acid through an
      adsorption process. Adsorption of citric acid over Al-MCM-41 shows the
      applicability of Freundlich and Langmuir isotherm and follows first order
      kinetics. The effects of contact time, concentration of citric acid, adsorbents
      (various Si/Al ratios of Al-MCM-41, Si-MCM-41, Hbeta zeolite and commercial
      carbon) and pH have been investigated. It has been found that the amount of
      citric acid adsorbed per unit gram of catalyst followed the order Al-MCM-41
      (Si/Al=30)>Al-MCM-41 (Si/Al=51)>activated charcoal>Al-MCM-41 (Si/Al=72)>Al-MCM-41
      (Si/Al=97)>Si-MCM-41>Hbeta zeolite.

PMID- 16289247
TI  - The role of wetlands in the chromophoric dissolved organic matter release and its
      relation to aquatic ecosystems optical properties. A case of study: Katonga and
      Bunjako Bays (Victoria Lake; Uganda).
AB  - Chromophoric Dissolved Organic Matter (CDOM) is an important component in
      freshwater and marine ecosystems and plays direct and indirect role in
      biogeochemical cycles. CDOM originates from the degradation process of organic
      materials, usually macrophytes and planktons. The present work examines the
      importance of wetland derived CDOM on the optical and bio-optical properties of
      two bays of Lake Victoria (Uganda, Africa). This was achieved by determining the
      attenuation and extinction coefficients of filtered and unfiltered water samples
      from two equatorial bays on the Ugandan coastline of Lake Victoria. Katonga Bay
      is a wetland lined bay that receives water from the Katonga river, while Bunjako
      Bay is an outer bay between Katonga Bay and Lake Victoria. The results showed
      that attenuation was highest in Katonga Bay and the role of CDOM is most dominant
      near the river inlet. The quantity and quality of CDOM is extremely different in
      the two bays: in Katonga Bay it is possible to hypothesize a terrestrial origin
      of CDOM (transported by the wetland river). On the contrary, in Bunjako Bay,
      spectral measurements of absorption indicate a modified CDOM and/or alternative
      CDOM source. The terrestrial CDOM in Katonga Bay is more capable of absorbing
      harmful UV radiation than the CDOM present in the Bunjako Bay. The resulting
      optical environment in the former bay presented a water column with a very
      limited penetration of harmful UV radiation, while a higher penetration was
      observed in the Bunjako Bay.

PMID- 16289248
TI  - Effect of TBT on Ruditapes decussatus juveniles.
AB  - The effects of sublethal concentrations of tributyltin (TBT) on growth of
      juvenile clams Ruditapes decussatus were determined during exposure to TBT
      concentrations of 50, 100 and 250 ng l(-1) (as Sn) for a period up to two years.
      Length and weight of clams increased continuously in all treatments throughout
      the experimental period, and, overall, rates were not significantly influenced by
      TBT exposure, although final length and weight were inversely related to
      increasing TBT concentration. Juvenile R. decussatus therefore appear to be less
      sensitive to TBT than larval stages. Some juveniles exposed to TBT developed
      abnormal shell growth, laterally, changing the typical flattened shape of clams
      into a more "rounded" form. This characteristic was more visible in the anterior
      margins of valves than posteriorly, and mainly observed in clams exposed to TBT
      at 50 ng l(-1) (as Sn).

PMID- 16289249
TI  - Regulation of m1 muscarinic receptors and nNOS mRNA levels by autoantibodies from
      schizophrenic patients.
AB  - In this paper we demonstrate that, circulating antibodies from schizophrenic
      patients interacting with cerebral M1 muscarinic acetylcholine receptors (M1
      mAChRs), can act as an inducer of m1 mAChR-mRNA, and neuronal nitric oxide
      synthase (nNOS) mRNA gene expression of rat frontal cortex. The different
      signaling pathways involved in the autoantibody's actions, were characterized. As
      previously reported serum autoantibodies from schizophrenic patients reacted
      against neural cells surface inhibiting the binding of the specific mAChR
      radioligand to rat cerebral frontal cortex membrane. Moreover, by ELISA using M1
      synthetic peptide (with identical aminoacid sequence to human M1 mAChR) as
      coating antigen we demonstrated the reactivity against the second extracellular
      loop of human cerebral M1 mAChR. The corresponding affinity-purified anti M1
      peptide IgG (anti M1 peptide IgG) from schizophrenic patients by stimulation of
      M1 mAChR exerted an increase in m1 mAChR-mRNA and nNOS-mRNA levels, that
      significantly correlated with the accumulation of phosphoinositides (IPs) and
      activation of NOS (alpha = 0.05). All these effects were blunted by pirenzepine
      and mimicked the action of the authentic agonist. Concurrent analysis of the
      effects of nNOS, phospholipase C (PLC) and calcium/calmodulin (CaM) inhibition on
      both, m1 mAChR-mRNA and nNOS-mRNA levels, showing that antibody up-regulation
      mRNA level is under the control of endogenous nitric oxide (NO) signaling system.
      On the basis of our results, the activation of M1 mAChR by schizophrenic
      autoantibody appears to induce nNOS-mRNA expression and reciprocally, the
      activation of NOS up-regulates m1 mAChR gene expression. These results gave
      support to the participation of an autoimmune process in a particular group of
      chronic schizophrenic patients.

PMID- 16289250
TI  - Prostaglandin D2 mediates neuronal damage by amyloid-beta or prions which
      activates microglial cells.
AB  - Microglial cells killed neurons damaged following incubation with sub-lethal
      concentrations of peptides derived from either the human prion protein (HuPrP82
      146) or amyloid-beta1-42 (a peptide found in Alzheimer's disease). HuPrP82-146 or
      amyloid-beta1-42 induced phenotypic changes in neurons that caused them to bind a
      CD14-IgG chimera. In co-cultures microglial cells produced interleukin (IL)-6 in
      response to HuPrP82-146 or amyloid-beta1-42 damaged neurons. The binding of the
      CD14-IgG chimera to HuPrP82-146 or amyloid-beta1-42 damaged neurons was reduced
      by pre-treatment with cyclo-oxygenase (COX)-1 inhibitors and in co-cultures, COX
      1 inhibitors significantly increased neuronal survival. Studies with individual
      prostaglandins demonstrated that the addition of prostaglandin D2, or
      prostaglandin E2, but not other prostaglandins (F2alpha, H2, I2 or 15-dJ2),
      mimicked the effects of amyloid-beta1-42 on neurons. Thus, prostaglandin D2 or E2
      damaged neurons bound the CD14-IgG chimera, and in co-cultures prostaglandin D2
      damaged neurons activated microglial cells. These effects were mediated via the
      DP prostanoid receptor; DP receptor agonists BW245C or SQ27986 induced neuronal
      damage, while the DP receptor antagonist BWA868C was neuroprotective in co
      cultures. These results indicate that prostaglandin D2, produced following
      activation of COX-1 by sub-lethal concentrations of HuPrP82-146 or amyloid-beta1
      42, causes phenotypic changes in neurons that activates microglial cells and
      leads to neuronal loss.

PMID- 16289251
TI  - Temporal dynamics of dissolved and particulate organic carbon in the northern
      Adriatic Sea in relation to the mucilage events.
AB  - The accumulation of dissolved and particulate organic matter may play an
      important role in mucilage formation in the northern Adriatic. Distributions of
      dissolved and particulate organic carbon were therefore investigated during the
      period June 1999-July 2002, when massive mucilage events occurred: in the summer
      of 2000 and, to a greater extent, of 2002. The seasonal variations in dissolved
      organic carbon (DOC) concentrations were significant, doubling in summer (up to
      150 micromol L(-1)) with respect to winter. The particulate organic carbon (POC)
      variations were also very large, with a less pronounced seasonal pattern compared
      to DOC, because the POC changes are much more dependent both on river discharges
      and on phytoplankton blooms. The comparison of the concentrations between the
      period before (March-May) and after the onset of mucilage events (June-August)
      showed that DOC, but particularly POC, were higher in the period before the event
      of 2002, more markedly in the surface waters of low salinity. The POC increased,
      reaching mean concentrations of up to 36 micromol L(-1) in March 2002 before the
      outbreak of the massive mucilage formation in June. This suggests that POC may
      have a more important role in the mucilage formation than DOC. The highest
      seasonal variations of organic matter concentrations took place in the upper
      layer of lower salinity, stressing the importance of stratification and
      pycnoclines for accumulation and aggregation of the organic matter in the
      northern Adriatic. The POC contribution to the total organic carbon was low in
      the oligotrophic waters (DOC/POC ratio >15) and increased with the phytoplankton
      biomass in the productive waters (DOC/POC ratio <10). Particulate organic carbon
      predominated over the dissolved inside the mucilage aggregate (DOC/POC ratio <1),
      probably because aggregation processes, in which colloidal organic carbon is
      involved, are important. The organic carbon within the aggregates reached a
      concentration of 13.6 mmol L(-1) which was about 100 times more than in the
      surrounding waters or in the waters when the mucilages were absent. This
      indicates that distributions of organic carbon in the northern Adriatic can be
      extremely patchy during mucilage events.

PMID- 16289252
TI  - Huntingtin fragmentation and increased caspase 3, 8 and 9 activities in
      lymphoblasts with heterozygous and homozygous Huntington's disease mutation.
AB  - Huntington's disease (HD) is caused by mutated huntingtin (htt), a toxic protein
      ubiquitously expressed in nervous and non-nervous system tissues. Fragmentation
      of htt by caspases and further accumulation in cells of protein aggregates
      contribute to cell dysfunction and death. In the attempt to elucidate whether
      this mechanism depends on patients' genotype, we analysed the pattern of htt
      fragmentation, the caspase 3, 8 and 9 activities and their variation in
      lymphoblasts with heterozygous and homozygous CAG mutation and in controls. Cells
      homozygous for expanded mutation showed greater amount of mutated fragments than
      heterozygotes and controls, caspase 3, 8 and 9 activities greater in mutated than
      control cell lines, after cyanide treatment, the caspase 3 and 8 particularly
      increased in homozygotes. This data offers a biological explanation to the
      clinical in-patients evidence of mutation homozygosity associated with more
      severe phenotype.

PMID- 16289254
TI  - Early detection of dementia in clinical practice.
AB  - Early identification of dementia and possible risk factors is a critical issue.
      The Basic Italian Cognitive Questionnaire (BICQ) is designed as a routine
      instrument for screening patients with initial cognitive impairment in daily
      practice. It is devoted to the general physician who needs a tool for deciding
      whether a subject deserves further diagnostic investigation in specialised
      centres. The administration of BICQ is easy, fast and does not require any
      training, since it is composed of 12 simple and ecologic questions referring to
      daily life. The discriminant analysis, a predictive model that generates a
      function based on linear combinations of the predictor variables, provided the
      best discrimination between controls with respect to the group of deteriorated
      patients. According to the classification function coefficients, the
      questionnaire score predicted correctly 100% of normal subjects and 85% of
      patients with cognitive impairment. Moreover, the receiving operating
      characteristics (ROC) analysis showed that the highest sensitivity and
      specificity were obtained at the cut-off value of 10. Thus, a <or=10 score was
      indicative of a possible cognitive impairment requiring further diagnostic work
      up. Among 963 randomly selected subjects from the general population over 50
      years of age, 130 subjects (13.5%) had a score <or=10. A complete diagnostic
      assessment was carried out in 103 of them. Forty-one (40%) resulted cognitively
      normal; 34 (33%) fulfilled the diagnostic criteria for mild cognitive impairment
      (MCI); 28 (27%) were diagnosed as demented.

PMID- 16289253
TI  - Aconitase is the main functional target of aging in the citric acid cycle of
      kidney mitochondria from mice.
AB  - The activities of the citric acid cycle enzymes were determined in mitochondria
      isolated from kidneys of relatively young, middle age, and old mice. Aconitase
      exhibited the most significant decrease in activity with age. The activity of
      alpha-ketoglutarate dehydrogenase exhibited a modest decrease in activity, while
      NADP(+)-isocitrate dehydrogenase (NADP(+)-ICD) activity increased moderately with
      age. Activities of citrate synthase, NAD(+)-isocitrate dehydrogenase (NAD(+)
      ICD), succinyl-CoA synthetase (SCS), succinate dehydrogenase (SD), fumarase
      (FUM), and malate dehydrogenase (MD) were not affected. The molar ratio of the
      intra-mitochondrial redox indicator, NADPH:NADP(+), was higher in young compared
      to old animals, while the NADH:NAD(+) molar ratio remained unchanged. It is
      suggested that an age-related decrease in aconitase activity along with
      relatively subtle alterations in activities of some other citric acid cycle
      enzymes are likely to contribute to a decline in the overall efficiency of
      mitochondrial bioenergetics. The biological consequences of such alterations
      include age-related fluctuations in the citric acid cycle intermediates, which
      are precursors of protein synthesis, activators of fatty acid synthesis, and can
      also act as ligands for orphan G-protein coupled receptors.

PMID- 16289255
TI  - Three sesquiterpene hydrocarbons from the roots of Panax ginseng C.A. Meyer
      (Araliaceae).
AB  - The volatile constituents of the roots of Panax ginseng C.A. Meyer have been
      investigated after hydrodistillation and analysed by means of different
      analytical methods. Besides several compounds already known three sesquiterpene
      hydrocarbons have been isolated from the essential oil. Structure elucidation of
      the bicyclic panaxene as well as of the tricyclic panaginsene and ginsinsene was
      performed by MS and NMR. They have been identified as (1R*,2S*,5S*)-2-ethenyl-1(1
      methylethenyl)-2,6,6-trimethylbicyclo[3.2.0]heptane (panaxene), (1S*,8S*,11R*)
      4,7,7,11-tetramethyltricyclo[6.3.0.0(1,5)]undec-4-ene (panaginsene) und
      (1R*,6R*,7R*)-3,7,10,10-tetramethyltricyclo[4.3.2.0(2,6)]undec-2-ene
      (ginsinsene).

PMID- 16289256
TI  - Factors affecting oligomerization status of UDP-glucose pyrophosphorylase.
AB  - UDP-glucose pyrophosphorylase (UGPase) is involved in the production of UDP
      glucose, a key precursor to polysaccharide synthesis in all organisms. UGPase
      activity has recently been proposed to be regulated by oligomerization, with
      monomer as the active species. In the present study, we investigated factors
      affecting oligomerization status of the enzyme, using purified recombinant barley
      UGPase. Incubation of wild-type (wt) UGPase with phosphate or Tris buffers
      promoted oligomerization, whereas Mops and Hepes completely dissociated the
      oligomers to monomers (the active form). Similar buffer effects were observed for
      KK127-128LL and C99S mutants of UGPase; however, the buffers had a relatively
      small effect on the oligomerization status of the LIV135-137NIN mutant, impaired
      in deoligomerization ability and showing only 6-9% activity of the wt. Buffer
      composition had no effect on UGPase activity at UGPase protein concentrations
      below ca. 20 ng/ml. However, at higher protein concentration the activity in
      Tris, but not Mops nor Hepes, underestimated the amount of the enzyme. The data
      suggest that oligomerization status of UGPase can be controlled by subtle changes
      in an immediate environment (buffers) and by protein dilution. The evidence is
      discussed in relation to our recent model of UGPase structure/function, and with
      respect to earlier reports on the oligomeric integrity/activity of UGPases from
      eukaryotic tissues.

PMID- 16289257
TI  - Cytotoxic clerodane diterpenes from Glossocarya calcicola.
AB  - Three clerodane diterpenes were isolated and identified from leaf extract of
      Glossocarya calcicola. Compound has been characterised as (rel)-10betaH-trans
      12xi-(2-methylbut-2(E)-enoyl)-1beta-(isobutanoyl)-6alpha,13xi-dihydroxyclerodan
      4(20),8(18)-dien-7,15-dione-15,16-oxide, to which we have assigned the trivial
      name calcicolin-A. The other two compounds had the same skeletal structure and C
      12 substituent but in compound, the C-1 esterifying group becomes 2-methylbut
      2(E)-enoic acid and in it becomes 2-methylbutanoic acid. Although anti-insect
      activity was not observed for G. calcicola, cytotoxicity against insect and human
      carcinoma cell lines was detected.

PMID- 16289258
TI  - Furostanol glycoside 26-O-beta-glucosidase from the leaves of Solanum torvum.
AB  - A beta-glucosidase (torvosidase) was purified to homogeneity from the young
      leaves of Solanum torvum. The enzyme was highly specific for cleavage of the
      glucose unit attached to the C-26 hydroxyl of furostanol glycosides from the same
      plant, namely torvosides A and H. Purified torvosidase is a monomeric
      glycoprotein, with a native molecular weight of 87 kDa by gel filtration and a pI
      of 8.8 by native agarose IEF. Optimum pH of the enzyme for p-nitrophenyl-beta
      glucoside and torvoside H was 5.0. Kinetic studies showed that Km values for
      torvoside A (0.06 3mM) and torvoside H (0.068 mM) were much lower than those for
      synthetic substrates, pNP-beta-glucoside (1.03 mM) and 4-methylumbelliferyl-beta
      glucoside (0.78 mM). The enzyme showed strict specificity for the beta-d-glucosyl
      bond when tested for glycone specificity. Torvosidase hydrolyses only torvosides
      and dalcochinin-8'-beta-glucoside, which is the natural substrate of Thai
      rosewood beta-glucosidase, but does not hydrolyse other natural substrates of the
      GH1 beta-glucosidases or of the GH3 beta-glucosidase families. Torvosidase also
      hydrolyses C5-C10 alkyl-beta-glucosides, with a rate of hydrolysis increasing
      with longer alkyl chain length. The internal peptide sequence of Solanum beta
      glucosidase shows high similarity to the sequences of family GH3 glycosyl
      hydrolases.

PMID- 16289259
TI  - Apoptotic and cell cycle regulatory markers in uterine leiomyosarcoma.
AB  - OBJECTIVES: The primary aim of this study was to investigate the expression of
      apoptotic and cell cycle regulators p53, p21, p27, bax, and bcl-2 in uterine
      leiomyosarcoma in order to identify molecular pathways that possibly could be
      important in the development of leiomyosarcoma. A secondary aim was to examine if
      the apoptotic and cell cycle regulatory protein expression profile of uterine
      leiomyosarcoma is potentially useful for clinical prognostic purposes. METHODS: A
      tissue microarray representing 36 uterine leiomyosarcomas and 19 uterine
      leiomyomas was created with 3 representative cores from each tumor.
      Immunohistochemical staining was performed for bcl-2, bax, p21, p27, and p53
      using standard techniques. Staining was scored 0-12 for each marker, 0-3 being
      negative and 4-12 positive. Outcome analyses were performed only for
      leiomyosarcomas. First recurrence was determined from the time of initial
      diagnosis. Survival was determined from the time of initial diagnosis to last
      follow-up. RESULTS: Associations were found between disease type (leiomyosarcoma
      vs. leiomyoma) and the positivity status of p21 (43% vs. 0%, P < 0.001), p53 (54%
      vs. 0%, P < 0.001), and bax (34% vs. 94%, P < 0.001). bcl-2-positive
      leiomyosarcoma was associated with a longer time to recurrence (P = 0.02) in a
      univariate analysis. In a multivariate analysis, tumor stage was the only
      independent significant prognostic factor (P = 0.002). CONCLUSION: The
      significant differential expression of apoptotic and cell cycle regulatory
      proteins in uterine leiomyosarcoma as compared to benign smooth muscle tumors
      suggests that pathways involving these proteins may be important in the
      development of malignant disease and, therefore, could be potential targets for
      molecular therapies.

PMID- 16289260
TI  - Effect of culture environment on gene expression and developmental
      characteristics in IVF-derived embryos.
AB  - It is generally accepted that mammalian preimplantation embryos are sensitive to
      their environment and that conditions of culture can affect future growth and
      developmental potential both pre- and postnatally. Evidence suggests that while
      culture conditions during bovine in vitro embryo production can impact somewhat
      on the developmental potential of the early embryo, the intrinsic quality of the
      oocyte is the key factor determining the proportion of oocytes developing to the
      blastocyst stage. In addition, evidence suggests that the period of post
      fertilization embryo culture is the most critical period affecting blastocyst
      quality assessed in terms of cryotolerance, gene expression pattern and ability
      to establish a pregnancy. This paper reviews the current literature, with
      emphasis on the bovine model, demonstrating evidence for an effect of post
      fertilization culture environment on embryo gene expression and quality.

PMID- 16289261
TI  - Improving fertility in beef cow recipients.
AB  - In the 1970s, bovine embryo transfer (ET) shifted from research in a laboratory
      environment to commercialization of this technology for beef producers. With the
      quarantine requirements and expense of importing Continental breeds of cattle
      from Europe, embryo transfer became the logical means to reproduce greater
      numbers of these animals at a lower cost. The ET industry grew very rapidly and
      soon would become what it is today, a common practice utilized by select ranchers
      and breeders. Research over the years has primarily focused on methods to
      increase the number of ovulations and fertilized ova from the donor female, but
      the total number of transferable embryos has not changed markedly in the last 20
      years. More recent advances have been in the area of in vitro production of
      embryos that allow for greater numbers of embryos to be produced and easier
      accessibility to incorporate technologies such as sexed sperm, sperm injection,
      or transgenics. This paper will focus on the second part of the equation, the
      recipient, and decisions that will enable both the customers and practitioners to
      most efficiently utilize embryos from superovulation, in vitro production, or
      nuclear transfer, so that the maximum number of pregnancies can be produced.

PMID- 16289262
TI  - Improving cryopreservation systems.
AB  - Cryopreservation of oocytes and embryos is a crucial step for widespread
      practical application of other techniques in domestic animal embryology. However,
      in contrast to the rapid development of procedures in the eighties and early
      nineties of the last century, new advancements with profound practical
      consequences have only been recently achieved. As a result of a long and
      controversial development, an alternative group of methods, vitrification, has
      proved its efficiency and practicality in the past few years. The aim of this
      short review is to characterize strategies to prevent cryoinjuries, summarize the
      development of vitrification, overview its recent achievements, and provide a
      perspective about possible application. Authors strongly believe that the future
      of mammalian oocyte and embryo cryopreservation will be mainly based on
      vitrification, and the rate of advancement will be determined by the rate by
      which embryologists learn and acknowledge this new approach.

PMID- 16289263
TI  - Effects of the dopamine agonist cabergoline on the pulsatile and TRH-induced
      secretion of prolactin, LH, and testosterone in male beagle dogs.
AB  - In the present study, the pulsatile serum profiles of prolactin, LH and
      testosterone were investigated in eight clinically healthy fertile male beagles
      of one to six years of age. Serum hormone concentrations were determined in blood
      samples collected at 15 min intervals over a period of 6 h before (control) and
      six days before the end of a four weeks treatment with the dopamine agonist
      cabergoline (5 microg kg(-1) bodyweight/day). In addition, the effect of
      cabergoline administration was investigated on thyrotropin-releasing hormone
      (TRH)-induced changes in the serum concentrations of these hormones. In all eight
      dogs, the serum prolactin concentrations (mean 3.0 +/- 0.3 ng ml(-1)) were on a
      relatively constant level not showing any pulsatility, while the secretion
      patterns of LH and testosterone were characterised by several hormone pulses.
      Cabergoline administration caused a minor but significant reduction of the mean
      prolactin concentration (2.9 +/- 0.2 ng ml(-1), p < 0.05) and did not affect the
      secretion of LH (mean 4.6 +/- 1.3 ng ml(-1) versus 4.4 +/- 1.7 ng ml(-1)) or
      testosterone (2.5 +/- 0.9 ng ml(-1) versus 2.4 +/- 1.2 ng ml(-1)). Under control
      conditions, a significant prolactin release was induced by intravenous TRH
      administration (before TRH: 3.8 +/- 0.9 ng ml(-1), 20 min after TRH: 9.1 +/- 5.9
      ng ml(-1)) demonstrating the role of TRH as potent prolactin releasing factor.
      This prolactin increase was almost completely suppressed under cabergoline
      medication (before TRH: 3.0 +/- 0.2 ng ml(-1), 20 min after TRH: 3.3 +/- 0.5 ng
      ml(-1)). The concentrations of LH and testosterone were not affected by TRH
      administration. The results of these studies suggest that dopamine agonists
      mainly affect suprabasal secretion of prolactin in the dog.

PMID- 16289264
TI  - A novel molecular genetic marker for gender determination of pigeons.
AB  - The absence of conspicuous sexual dimorphism in pigeons often makes it difficult
      to determine their sex on the basis of external morphology. We identified a novel
      female-specific DNA marker in pigeons, presenting the possibility of pigeon
      gender determination using a PCR-based method. One-hundred and twenty random
      primers were used for RAPD fingerprinting in order to find any sex-specific
      fragments in pigeons. One of these primers, OPC-20, produced a female-specific
      band in the DNA fingerprints. This DNA fragment was isolated from the gel and
      inserted into a vector for nucleotide sequencing. A novel female-specific 732 bp
      sequence was obtained. A pair of primers (DoveOPC20F & R) was designed, based on
      the cloned sequence, for amplifying the female-specific band by PCR for pigeon
      gender determination. Sex-specific bands in the gel were observed in all females
      but not in males. The PCR products in the gel were then transferred onto nylon
      membranes and hybridized with a DIG-labeled probe of the cloned female-specific
      DNA fragment. Clear hybridization signals were found only in all of the female
      pigeons; the same result was obtained from dot blot hybridization. This
      demonstrates that the sex of pigeons can be accurately and rapidly identified by
      PCR.

PMID- 16289265
TI  - Comparative nucleotide sequence analysis of the phosphoprotein gene of peste des
      petits ruminants vaccine virus of Indian origin.
AB  - The nucleotide sequences of the phosphoprotein (P) gene of peste des petits
      ruminants (PPRV) vaccine virus (PPRV Sungri/96) belongs to Asian lineage have
      been determined and the deduced amino acid sequences were compared with another
      vaccine strain PPRV/Nigeria75/1 and with those of the other morbilliviruses. The
      1652 nucleotides of the P gene encode a phosphoprotein of 509 amino acid residues
      (from nucleotide numbers 60 to 1587), which is 91% identical to that of
      PPRV/Nigeria75/1. The C protein consists of 177 amino acid residues and is 91%
      identical with that of PPRV/Nigeria75/1. The conserved mRNA editing site
      (5'TTAAAAGGGCACAG) was present at positions 742-756 in the P gene, which is
      conserved in all other morbilliviruses. The CTT trinucleotide sequence is present
      at the N/P and P/M intergenic region, which is totally conserved in
      morbilliviruses. This will be the third sequence for the P gene of PPRV since
      that of the vaccine strain and a wild-type Turkish isolate has been published
      already.

PMID- 16289266
TI  - Measurement and modelling of air pollution and atmospheric chemistry in the U.K.
      West Midlands conurbation: overview of the PUMA Consortium project.
AB  - The PUMA (Pollution of the Urban Midlands Atmosphere) Consortium project involved
      intensive measurement campaigns in the Summer of 1999 and Winter of 1999/2000,
      respectively, in which a wide variety of air pollutants were measured in the UK
      West Midlands conurbation including detailed speciation of VOCs and major
      component analysis of aerosol. Measurements of the OH and HO2 free radicals by
      the FAGE technique demonstrated that winter concentrations of OH were
      approximately half of those measured during the summer despite a factor of 15
      reduction in production through the photolysis of ozone. Detailed box modelling
      of the fast reaction chemistry revealed the decomposition of Criegee
      intermediates formed from ozone-alkene reactions to be responsible for the
      majority of the formation of hydroxyl in both the summer and winter campaigns, in
      contrast to earlier rural measurements in which ozone photolysis was predominant.
      The main sinks for hydroxyl are reactions with NO2, alkenes and oxygenates.
      Concentrations of the more stable hydrocarbons were found to be relatively
      invariant across the conurbation, but the impacts of photochemistry were evident
      through analyses of formaldehyde which showed the majority to be photochemical in
      origin as opposed to emitted from road traffic. Measurements on the upwind and
      downwind boundaries of the conurbation revealed substantial enhancements in NOx
      as a result of emissions within the conurbation, especially during westerly winds
      which carried relatively clean air. Using calcium as a tracer for crustal
      particles, it proved possible to reconstruct aerosol mass from the major chemical
      components with a fairly high degree of success. The organic to elemental carbon
      ratios showed a far greater influence of photochemistry in summer than winter,
      presumably resulting mainly from the greater availability of biogenic precursors
      during the summer campaign. Two urban airshed models were developed and applied
      to the conurbation, one Eulerian, the other Lagrangian. Both were able to give a
      good simulation of concentrations of both primary and secondary pollutants at
      urban background locations.

PMID- 16289267
TI  - Fetal infusions of plasma cause an increase in umbilical vascular resistance in
      sheep.
AB  - Earlier studies suggested that the fetal placental circulation is relatively
      inert with fetal placental flow increasing or decreasing with perfusion pressure.
      Subsequent studies have demonstrated that the placenta may not be an unreactive
      vascular bed. The present study was undertaken to determine if plasma infusion
      induced hypertension increased fetal placental flow in proportion to the driving
      pressure across the fetal placental circulation. Six fetal sheep were operated on
      at 118-122 days to place intravascular catheters and a flow sensor on the common
      umbilical artery. Starting 6 days later, the fetuses were infused with adult
      sheep plasma. During the 7-day-long infusion period, they received a total of
      1515+/-217 (SD) ml of fluid and 93.2+/-12.0 g of protein. Fetal plasma protein
      concentrations increased from 34.2+/-2.3 to 77.0+/-9.7 g/l (P<0.0001). Fetal
      arterial blood pressures rose from 42+/-3 to 59+/-4 mmHg (P<0.01) and venous
      pressures rose from 2.2+/-0.5 to 4.8+/-0.8 mmHg (P<0.01). In spite of the large
      increase in driving pressure, fetal placental blood flow remained (statistically)
      constant (627+/-299 ml/min and 552+/-221 ml/min) while fetal umbilical resistance
      increased from 0.077+/-0.038 to 0.115+/-0.053 mmHg min/ml (P<0.01). On day 7,
      plasma renin activity had fallen from 6.7+/-4.2 ng/(ml/h) at preinfusion control
      to 0.6+/-0.6 ng/(ml/h) (P<0.05) and plasma angiotensin-II concentration had
      fallen from 33.2+/-26.6 to 6.2+/-3.9 pg/ml, although this fall was not
      statistically significant (P=0.07). Fetal placental flow did not increase with
      increased driving pressure across the fetal placental circulation. The increase
      in fetal placental resistance may be a response to the increase in arterial
      pressure since there was no increase in flow.

PMID- 16289268
TI  - On the dynamics of dengue epidemics from large-scale information.
AB  - A model for the spatial and temporal dynamics of dengue fever is proposed in this
      article. The vector population dynamics is derived from a diffusion equation that
      is based on environmental parameters at the scale of a remote-sensing image.
      Vectors and hosts populations are then classically divided into compartments
      corresponding to their respective disease status. The transmission processes
      between hosts and vectors are described by a set of differential equations. The
      link between the vector population diffusion model and the compartmental model
      enables one to describe both the spatial and temporal dynamics of the disease.
      Simulations in artificial and actual landscapes show the advantage of using
      remotely sensed and complementary meteorological data for modelling in a
      realistic way the geographic spread of a vector-borne disease such as dengue
      fever.

PMID- 16289269
TI  - Overexpression of junctin causes adaptive changes in cardiac myocyte Ca(2+)
      signaling.
AB  - In cardiac muscle, junctin forms a quaternary protein complex with the ryanodine
      receptor (RyR), calsequestrin, and triadin 1 at the luminal face of the
      junctional sarcoplasmic reticulum (jSR). By binding directly the RyR and
      calsequestrin, junctin may mediate the Ca(2+)-dependent regulatory interactions
      between both proteins. To gain more insight into the underlying mechanisms of
      impaired contractile relaxation in transgenic mice with cardiac-specific
      overexpression of junctin (TG), we studied cellular Ca(2+) handling in these
      mice. We found that the SR Ca(2+) load was reduced by 22% in cardiomyocytes from
      TG mice. Consistent with this, the frequency of Ca(2+) sparks was diminished by
      32%. The decay of spontaneous Ca(2+) sparks was prolonged by 117% in TG. This
      finding was associated with a lower Na(+)-Ca(2+) exchanger (NCX) protein
      expression (by 67%) and a higher basal RyR phosphorylation at Ser(2809) (by 64%)
      in TG. The shortening- and Delta[Ca](i)-frequency relationships (0.5-4 Hz) were
      flat in TG compared to wild-type (WT) which exhibited a positive staircase for
      both parameters. Furthermore, increasing stimulation frequencies hastened the
      time of relaxation and the decay of [Ca](i) by a higher percentage in TG. We
      conclude that the impaired relaxation in TG may result from a reduced NCX
      expression and/or a higher SR Ca(2+) leak. The altered shortening-frequency
      relationship in TG seems to be a consequence of an impaired excitation
      contraction coupling with depressed SR Ca(2+) release at higher rates of
      stimulation. Our data suggest that the more prominent frequency-dependent
      hastening of relaxation in TG results from a stimulation of SR Ca(2+) transport
      reflected by corresponding changes of [Ca](i).

PMID- 16289271
TI  - Ocular motor outcomes after bilateral and unilateral infantile cataracts.
AB  - We wished to study how the severity and duration of early onset visual
      deprivation affects eye alignment and ocular stability. Thirty-three patients
      (aged 1 week to 12.8 years) with infantile cataracts (16 bilateral, 17
      unilateral) were examined for periods up to 61 months. Twenty-three patients were
      considered to have cataracts, which were a major obstacle to vision (major form
      deprivation), 9 of whom underwent surgery within 8 weeks of birth (mean and
      SD=5.2+/-2.3 weeks) and 10 after 8 weeks (mean and SD=33.9+/-29.7 months). Eye
      alignment and fixation stability was measured using infrared recording systems
      and video. Visual acuity was assessed using forced-choice preferential looking
      techniques in the neonates and infants and with optotypes in the children.
      Fifteen of the 23 (65%) patients who experienced major form deprivation exhibited
      a nystagmus, of which 11 (73%) were manifest latent nystagmus (MLN). Nineteen of
      the 23 (85%) had strabismus. Of the nine patients who underwent early surgery (<
      or =8 weeks), two displayed a preoperative nystagmus whilst between 10 and 39
      months post-operatively 8 (89%) exhibited a nystagmus. Of the group of 10
      patients with minor cataracts only 2 (1 late surgery, 1 no surgery) had nystagmus
      and 2 strabismus. We conclude that following optimal post-operative management of
      infantile cataracts a sustained nystagmus--typically an MLN--is the most likely
      ocular motor outcome, even when the period of deprivation is as short as 3 weeks.

PMID- 16289270
TI  - Calcium release from ryanodine receptors in the nucleoplasmic reticulum.
AB  - Ca(2+) signals control DNA synthesis and repair, gene transcription, and other
      cell functions that occur within the nucleus. The nuclear envelope can store
      Ca(2+) and release it into the nucleus via either the inositol 1,4,5
      trisphosphate receptor (InsP3R) or the ryanodine receptor (RyR). Furthermore,
      many cell types have a reticular network within their nuclei and InsP3Rs on this
      nucleoplasmic reticulum permit local subnuclear control of Ca(2+) signals and
      Ca(2+)-dependent intranuclear events. However, it is unknown whether RyR
      similarly is expressed on the nucleoplasmic reticulum and can control subnuclear
      Ca(2+) signals. Here we report that the type 1 RyR is expressed on intranuclear
      extensions of the sarcoplasmic reticulum of C2C12 cells, a skeletal muscle
      derived cell line. In addition, two-photon photorelease of caged Ca(2+) in the
      region of the nucleoplasmic reticulum evoked Ca(2+)-induced Ca(2+) release (CICR)
      within the nucleus, which could be suppressed by the RyR inhibitor dantrolene.
      These results show that intranuclear extensions of the nuclear envelope have
      functional RyR and provide a possible mechanism whereby cells expressing RyR can
      regulate Ca(2+) signals in discrete regions within the nucleus.

PMID- 16289272
TI  - Visual mismatch negativity elicited by magnocellular system activation.
AB  - The processing of visual motion was tested by means of event related potentials
      recording (ERP) using a paradigm designed to produce a visual mismatch negativity
      effect. The stimuli were unattended and presented in the peripheral visual field
      (outside the central 15 degrees). The standard stimulus consisted of an up/down
      motion sequence, whilst the deviant stimulus of a down/up motion sequence.
      Significant ERP differences between the standard and deviant conditions were
      found in 8 out of 10 adult subjects already in 80 ms and prevailingly in interval
      145-260 ms from the initial stimulus presentation. The results demonstrate that
      the magnocellular information undergoes processing capable of detecting
      differences in the sequence of unattended peripheral motion stimuli.

PMID- 16289273
TI  - ZENK expression of retinal glucagon amacrine cells in chicks: the effect of
      defocus presented in vivo, in vitro and under anesthesia.
AB  - PURPOSE: The transcription factor ZENK, expressed in glucagon amacrine cells in
      the retina in the chicken, has been shown to respond selectively to the sign of
      imposed defocus. To find out whether the retina by itself is able to perform the
      underlying image processing, we used ZENK to probe responses of amacrine cells to
      defined amounts of imposed defocus, both in vitro and in vivo. METHODS: To
      stimulate in vitro, retinal punches (8mm diameter), whole eyecups, or complete
      excised globes were stimulated with digitally generated video movies that were
      presented with defined amounts of defocus for 15, 30 or 45 min. Infrared
      photoretinoscopy was used to control the defocus of the projected movies.
      Furthermore, both anesthetized and alert chickens were stimulated with the
      differently focused video movies, or they were exposed to the visual environment
      of the laboratory for 4 days, wearing spectacle lenses for 45 or 90 min per day.
      Anesthetic effects per se were determined by using two different anesthetic
      protocols. After the stimulation, ZENK-immunoreactivity in glucagon amacrine
      cells was quantified. Eye growth and refractive development were recorded by A
      scan ultrasound and infrared photoretinoscopy, respectively. RESULTS: In the
      isolated retina (stimulated in vitro), no consistent changes in ZENK expression
      could be induced by defocus, with a baseline expression similar in alert chicks.
      Placing a diffuser into the light path during optical stimulation did not lower
      ZENK expression, although diffusers are known to reduce ZENK expression in alert
      chicks. Imposed defocus in vitro caused merely a higher variability in ZENK
      expression in some cases. Defocus produced significant changes in ZENK expression
      only in the case of 4D of imposed hyperopia, but these changes were in the
      opposite direction to what was previously observed in vivo. Also in isolated eye
      cup or eye balls, no changes in ZENK expression could be induced by defocus. Most
      strikingly, neither ZENK expression, nor eye growth were affected by imposing
      defocus under anesthesia. Only alert chickens displayed the expected changes in
      ZENK expression and eye growth during imposed defocus, both with video
      stimulation and the "real world". CONCLUSIONS: In vitro, the chicken retina can
      still process some spatial features (since ZENK expression in the isolated retina
      was changed by imposed defocus with video stimulation), but the directions of the
      changes were no longer related to the sign of defocus. Also in intact animals,
      though under anesthesia, ZENK and eye growth did not respond to the sign of
      imposed defocus. Some stimulus for emmetropization appears to be important which
      is available only in alert animals.

PMID- 16289274
TI  - Progressive N170 habituation to unattended repeated faces.
AB  - This study utilized a location-matching task to investigate whether the face
      sensitive N170 event-related potential component would habituate in its response
      to the repeated presentation of same face stimuli when face identity was
      irrelevant to the experimental task. N170 amplitude decreased progressively with
      repeated presentation of the same face vs. sequential presentation of novel
      faces. This N170 habituation to face identity repetition occurred only for faces
      at unattended spatial locations, likely representing a relatively pure
      observation of automatic early face processing.

PMID- 16289275
TI  - Backscroll illusion: apparent motion in the background of locomotive objects.
AB  - Backscroll illusion is an apparent motion perceived in backgrounds of movie
      images that present locomotive objects such as people, animals, and vehicles.
      This illusion is from the visual system registering retinal motion signals in
      relation to high-level object motion signals. We confirmed this notion from
      psychophysical experiments that mainly presented a realistic human figure on a
      treadmill walking or running in front of a counterphase grating. The apparent
      grating motion was consistently induced in the direction opposite to the
      locomotion. The induction was tuned to a gait velocity. The time course showed
      that the illusion arose as if it was synchronized with gait recognition, and that
      it was sustained against several reversals of limb swings so that local motion
      accounts were denied. A weak but significant illusion was observed from a static
      figure that implied a gait. Thus, we concluded that the illusion was determined
      by the high-level recognition of biological motion. An additional experiment
      found a similar effect from a vehicle with rotating wheels but no induction from
      a rotating wheel per se. This result led us to hypothesize that the backscroll
      illusion is generalized to objects that have shapes implying their moving
      directions.

PMID- 16289276
TI  - A DNA vaccine coding for gB and gD of pseudorabies virus (suid herpes type 1)
      primes the immune system in the presence of maternal immunity more efficiently
      than conventional vaccines.
AB  - DNA vaccines are capable of priming the immune system of neonates in the presence
      of maternal antibodies. However, it is still not clear whether the extent of
      priming and protection against challenge infections induced by a DNA vaccine in
      maternally immune newborns is better than that induced by conventional vaccines.
      To study this, we used the pseudorabies virus (PRV) infection model in the
      natural host, the pig. We compared the efficacy of a DNA vaccine with the
      efficacy of a conventional modified live vaccine (MLV) and an inactivated vaccine
      (IV) in maternally immune newborn piglets. We measured the priming of the immune
      response and the degree of protection against challenge infection for all vaccine
      types. We vaccinated piglets with or without maternal immunity twice, at the age
      of 5 and 9 weeks, and we assessed protection by challenge infection with virulent
      PRV at the age of 15 weeks. Vaccination with DNA or conventional vaccines induced
      both humoral and cell-mediated immune responses in maternally immune animals. DNA
      vaccination seemed not to suffer from suppression by maternal immunity and
      resulted in similar or stronger immune responses in maternally immune piglets as
      compared in naive piglets. In contrast, vaccination with conventional vaccines
      resulted in weaker immune responses in maternally immune piglets than in naive
      piglets. Moreover, DNA vaccination provided better protection against challenge
      infection in maternally immune piglets than in naive piglets, whereas vaccination
      with conventional vaccines did not.

PMID- 16289277
TI  - An autoimmune domain-reduced HCV core gene remains effective in stimulating anti
      core cytotoxic T lymphocyte activity.
AB  - Chronic hepatitis C virus (HCV) infection cases resistant to conventional
      therapies might be treated by immunotherapy as cytotoxic T lymphocytes (CTL) are
      the main mechanism through which viral infections are cleared. The HCV core gene,
      with the highest homology between HCV types, deleted of its autoimmune
      stimulating regions (pseudo-GOR and pseudo-p450), may be an appropriate antigen
      for targeting HCV-infected cells. Two recombinant adeno-associated virus (rAAV)
      vectors, carrying either the full length (aa 1-190) or truncated (aa 49-180,
      deleted of the pseudo-GOR and pseudo-p450 sequences) versions of core, were
      generated. Both AAV/core (l-190) and AAV/core (49-180) were used to
      transduce/load dendritic cells (DC) at high levels (88-95%). These two
      genetically altered DC types then stimulated anti-core CTL. The DC and CTL were
      analyzed by FACS and for killing efficiency (percent target killing). The rAAV
      altered DC displayed higher levels of CD80, CD83, CD86, and CD 1a than control
      DC. The truncated core (aa 49-180) gene stimulated equivalent and strong killing
      of synthetic core-positive autologous peripheral blood lymphocyte (PBL) targets
      to that stimulated by the full length core gene. However, the smaller core (49
      180) antigen gene stimulated lower levels of killing of core-negative "self" PBL
      targets (GOR- and p450-positive) (p = 0.002). These AAV/core: DC-stimulated CTL
      displayed higher IFN-gamma expression, higher CD8:CD4 ratios, and lower CD56:CD8
      ratios than controls. The rAAV-loading derived CD8+ T cells had more CD69+ cells
      and the CD4+ T populations had fewer CD25+ cells than controls. We conclude that
      the core (49-180) gene is an effect antigen, but has the advantage of stimulating
      less self-recognition. Thus, core (49-180) may be useful for further
      translational immunotherapy studies against HCV.

PMID- 16289279
TI  - An exposure-based risk assessment approach to confirm the safety of hydrogen
      peroxide for use in home tooth bleaching.
AB  - Hydrogen peroxide has a long history of safe use in a wide variety of medical and
      consumer products, including oral care products. The use of hydrogen peroxide in
      tooth bleaching has been extended to home use. Because this represents a new use,
      questions have been raised regarding safety, particularly the potential for
      peroxide tooth-whitening products to increase the risk of oral cancer in high
      risk individuals (e.g., smokers and drinkers). These concerns are based on
      limited experimental data in animals that hydrogen peroxide has extremely weak
      tumor promoting activity and a lack of publicly available data on exposure to
      peroxides from the home use of tooth-whitening products. This paper provides a
      weight-of-evidence cancer hazard characterization for hydrogen peroxide and
      presents a quantitative risk assessment that confirms a favorable human safety
      profile risk associated with low levels of exposure to hydrogen peroxide from the
      use of tooth-whitening products. This includes a lack of tumor promotion risk
      which is important because tooth-whitening products are often used by chronic
      smokers and drinkers, who may represent a susceptible subpopulation because of
      their exposure to other known carcinogens.

PMID- 16289278
TI  - Localization of opioid receptor antagonist [3H]-LY255582 binding sites in mouse
      brain: comparison with the distribution of mu, delta and kappa binding sites.
AB  - Agonist stimulation of opioid receptors increases feeding in rodents, while
      opioid antagonists inhibit food intake. The pan-opioid antagonist, LY255582,
      produces a sustained reduction in food intake and body weight in rodent models of
      obesity. However, the specific receptor subtype(s) responsible for this activity
      is unknown. To better characterize the pharmacology of LY255582, we examined the
      binding of a radiolabeled version of the molecule, [(3)H]-LY255582, in mouse
      brain using autoradiography. In mouse brain homogenates, the K(d) and B(max) for
      [(3)H]-LY255582 were 0.156 +/- 0.07 nM and 249 +/- 14 fmol/mg protein,
      respectively. [(3)H]-LY255582 bound to slide mounted sections of mouse brain with
      high affinity and low non-specific binding. High levels of binding were seen in
      areas consistent with the known localization of opioid receptors. These areas
      included the caudate putamen, nucleus accumbens, claustrum, medial habenula,
      dorsal endopiriform nucleus, basolateral nucleus of the amygdala, hypothalamus,
      thalamus and ventral tegmental area. We compared the binding distribution of
      [(3)H]-LY255582 to the opioid receptor antagonist radioligands [(3)H]-naloxone
      (mu), [(3)H]-naltrindole (delta) and [(3)H]-norBNI (kappa). The overall
      distribution of [(3)H]-LY255582 binding sites was similar to that of the other
      ligands. No specific [(3)H]-LY255582 binding was noted in sections of mu-, delta-
      and kappa-receptor combinatorial knockout mice. Therefore, it is likely that
      LY255582 produces its effects on feeding and body weight gain through a
      combination of mu-, delta- and kappa-receptor activity.

PMID- 16289280
TI  - Comparative studies on potential of consortium and constituent pure bacterial
      isolates to decolorize azo dyes.
AB  - The decolorization potential of the consortium HM-4 constituted by mixing four
      laboratory isolates identified as Bacillus cereus (BN-7), Pseudomonas putida (BN
      4), Pseudomonas fluorescens (BN-5) and Stenotrophomonas acidaminiphila (BN-3) was
      compared with that of individual isolates. Six different azo dyes viz., C.I. Acid
      Red 88 (AR-88), C.I. Acid Red 119 (AR-119), C.I. Acid Red 97 (AR-97), C.I.
      Reactive Red 120 (RR-120), C.I. Acid Blue 113 (AB-113) and C.I. Acid Brown 100
      (AB-100) were used in this study. The individual bacterial isolates were not able
      to completely decolorize these dyes, except for dyes AR-119 and AB-113. The
      consortium HM-4 was able to decolorize all the dyes used at an initial dye
      concentration of 20 mg L(-1) at a significantly higher rate as compared to that
      achieved by individual isolates.

PMID- 16289281
TI  - Ozonation of the marine dinoflagellate alga Amphidinium sp.--implications for
      ballast water disinfection.
AB  - Ozone has been investigated for its potential to remove marine dinoflagellate
      algae from ships' ballast water. Dinoflagellate algae, Amphidinium sp. isolated
      from the Great Barrier Reef, Townsville, Australia were used as indicators since
      these produce a type of cyst that is difficult to inactivate, but are relatively
      easy to culture. The ozonation experiments have demonstrated a high ozone demand
      for inactivation of the algal cultures, which increases as the culture ages. The
      main ozone demand in seawater is due to its reaction with bromide to form bromine
      compounds. The non-bromide ozone demand has been estimated by measuring the
      residuals produced after various doses of ozone. The Amphidinium sp. show an
      unexpected response to both ozonation and bromination, with an instantaneous
      inactivation of the organisms for all doses that produced an oxidant residual in
      the seawater, followed by an effect of the disinfection residual. The standard
      design procedure of comparing Ct will not be effective for predicting the
      response of the organism to varying dose, C, and contact time, t, and a plot of
      ozone produced oxidant residual against organism inactivation for various contact
      times is proposed for design purposes. High doses of ozone (5-11 mg/L) and up to
      6h of residual contact were required for a 4-log inactivation of the Amphidinium
      sp. Ozonation is likely to be a difficult technology to implement for organisms
      with this ozone requirement in combination with characteristics of ballast tanks,
      which contain areas of sediments high in detritus and areas of corrosion.

PMID- 16289283
TI  - Brain mechanisms of aggressive behavior: an updated review.
AB  - During the 25 years since a motivational systems model was proposed to explain
      the brain mechanisms of aggressive behavior (D.B. Adams. Brain mechanisms for
      offense, defense, and submission. Behav. Brain. Sci. 2, (1979a) 200-241)
      considerable research has been carried out. Updating the model in the light of
      this research requires several changes. A previous distinction between submission
      and defense systems is abandoned and, instead, it is proposed that two distinct
      subsets of the defense motivational mechanism may be recognized, one for anti
      predator defense and the other for consociate defense. Similarly, the offense
      motivational mechanism is now considered to have at least two subsets, one
      mediating territorial and the other competitive fighting. Data continue to
      indicate that the defense motivational mechanism is located in the midbrain
      central gray and adjoining tissue. Also data tend to support the hypothesis that
      the offense motivational mechanism is located in the hypothalamus at the level of
      the anterior hypothalamus. Consideration is also given to a motivational system
      for patrol/marking which is related to aggressive behavior. Research is reviewed
      that bears on the neural structure of motivating and releasing/directing stimuli
      and motor patterning mechanisms of offense, defense and patrol/marking, as well
      as the location of learning and hormonal effects, and attention is given to how
      the model can be tested.

PMID- 16289282
TI  - The neurobiological basis of temperament: towards a better understanding of
      psychopathology.
AB  - The ability to characterise psychopathologies on the basis of their underlying
      neurobiology is critical in improving our understanding of disorder etiology and
      making more effective diagnostic and treatment decisions. Given the well
      documented relationship between temperament (i.e. core personality traits) and
      psychopathology, research investigating the neurobiological substrates that
      underlie temperament is potentially key to our understanding of the biological
      basis of mental disorder. We present evidence that specific areas of the
      prefrontal cortex (including the dorsolateral prefrontal, anterior cingulate, and
      orbitofrontal cortices) and limbic structures (including the amygdala,
      hippocampus and nucleus accumbens) are key regions associated with three
      fundamental dimensions of temperament: Negative Affect, Positive Affect, and
      Constraint. Proposed relationships are based on two types of research: (a)
      research into the neurobiological correlates of affective and cognitive processes
      underlying these dimensions; and (b) research into the neurobiology of various
      psychopathologies, which have been correlated with these dimensions. A model is
      proposed detailing how these structures might comprise neural networks whose
      functioning underlies the three temperaments. Recommendations are made for future
      research into the neurobiology of temperament, including the need to focus on
      neural networks rather than individual structures, and the importance of
      prospective, longitudinal, multi-modal imaging studies in at-risk youth.

PMID- 16289284
TI  - Assessment of reproductive toxicity in male rats following acute and sub-chronic
      exposures to diphenyl diselenide and diphenyl ditelluride.
AB  - The present study was conducted to evaluate the toxicity of the exposure to
      diphenyl diselenide [(PhSe)2] and diphenyl ditelluride [(PhTe)2] on reproductive
      system in Wistar rats. Adult male rats were exposed intraperitonealy (acute) or
      subcutaneously (sub-chronic, during 4 or 8 weeks) to (PhSe)2 or (PhTe)2 prior to
      mating. A number of biochemical parameters in rat testes were examined, such as
      delta-aminolevulinate dehydratase (delta-ALA-D) activity, lipid peroxidation,
      glycogen content and components of the antioxidant defenses (superoxide dismutase
      (SOD) activity and ascorbic acid concentration). Furthermore, a possible effect
      on fertility and reproductive performance in male rats were studied. Sperm counts
      of caudal epididymis were also evaluated. No lethality was noted in any group.
      Reduction on body weight in rats which received (PhTe)2 was only evidenced in
      acute exposure, while (PhSe)2-exposed rats presented significant loss of body
      weight in acute and 4 week-exposure. Mating and fertility indexes were not
      affected after acute and sub-chronic exposure. Regarding other parameters
      studied, except for a decrease in testes glycogen content in acutely (PhSe)2
      treated group, no alterations were found in treated groups. Sperm counts of rats
      treated acutely and sub-chronically were unaffected by drugs exposure.
      Histological evaluation revealed no modification on testicular tissue in rats
      exposed to (PhSe)2 and (PhTe)2. The results suggest the absence of the male
      reproductive toxicity induced by (PhSe)2 and (PhTe)2 administered
      intraperitonealy (acute) or subcutaneously (sub-chronical) to adult rats Wistar.

PMID- 16289285
TI  - Estimation and projection of nitrous oxide (N2O) emissions from anthropogenic
      sources in Taiwan.
AB  - Taiwan is a densely populated and developed country with more than 97% of energy
      consumption supplied by imported fuels. Greenhouse gas emissions are thus
      becoming significant environmental issues in the country. Using the
      Intergovernmental Panel on Climate Change (IPCC) recommended methodologies,
      anthropogenic emissions of nitrous oxide (N2O) in Taiwan during 2000-2003 were
      estimated to be around 41 thousand metric tons annually. About 87% of N2O
      emissions come from agriculture, 7% from the energy sector, 3% from industrial
      processes sector, 3% from waste sector. On the basis of N2O emissions in 2000,
      projections for the year 2010 show that emissions were estimated to decline by
      about 6% mainly due to agricultural changes in response to the entry of WTO in
      2002. In contrast to projections for the year 2020, N2O emissions were projected
      to grow by about 17%. This is based on the reasonable scenario that a new adipic
      acid/nitric acid plant will be probably started after 2010.

PMID- 16289286
TI  - Increased levels of polychlorobiphenyls in Italian women with endometriosis.
AB  - Endometriosis has been hypothesised to be linked to persistent and toxic
      organochlorinated chemicals. Dioxins and dioxin-like compounds have in particular
      been associated with the disease, mainly on the basis of experimental studies.
      Data in women are conflicting. A case-control study on 80 Italian nulliparous
      women of reproductive age was carried out to assess whether there is a
      correlation between the presence of endometriosis and blood levels of
      polychlorobiphenyls (PCBs), a family of ubiquitary environmental pollutants which
      comprises congeners with dioxin-like activity. Higher levels of PCBs were found
      in women with endometriosis. A mean cumulative value of 410 ng g(-1), lipid base,
      was found in cases versus the value of 250 ng g(-1) observed in the control group
      (odds ratio for upper tertile 4.0, CI 95% 1.3-13; p = 0.0003). PCB increase
      involved both dioxin-like (PCBs 105, 118, 156, and 167) and non-dioxin-like
      congeners (PCBs 101, 138, 153, 170, 180).

PMID- 16289287
TI  - Sensitivities of Australian and New Zealand amphipods to copper and zinc in
      waters and metal-spiked sediments.
AB  - The sensitivities of eight benthic amphipods, Chaetocorophium cf. lucasi,
      Corophium colo, Grandidierella japonica, Hyale crassicornis, Hyale longicornis,
      Melita awa, Melita matilda and Melita plumulosa, to copper and zinc in water-only
      and whole-sediment toxicity tests were compared. Whole-sediment tests used copper
      (1300 mg/kg) and zinc- (4000 mg/kg) spiked sediments after equilibration for
      sufficient time to produce pore water and overlying water concentrations below
      the lowest observable effect concentrations of water-only exposures. Survival of
      adults (after 10 d) and juveniles (after 96 h), and the metal concentrations in
      the body tissues of adults, were determined at the end of the tests. Two
      epibenthic amphipods from the genus Melita were the most sensitive species to
      aqueous copper and zinc, with a 96-h LC50 value of 120 microg Cu/l for both M.
      awa and M. plumulosa juveniles, and a 96-h LC50 value of 640 microg Zn/l for
      juveniles of M. plumulosa. Juvenile amphipods (7-d old) were more sensitive than
      adult amphipods (>30-d old) in both water-only and whole-sediment tests, with
      adult-LC50/juvenile-LC50 ratios in water-only tests ranging from 1.2 to l.5 for
      copper and 1 to 1.4 for zinc. All species except C. colo, C. cf. lucasi and M.
      matilda were sensitive to the copper-spiked sediment, with survival between 14%
      and 74% of controls. Similarly, all species except C. colo and G. japonica,
      showed a response to the zinc-spiked sediment (26-81% of control survival). The
      epibenthic amphipods were more sensitive than the infaunal tube-dwelling
      amphipods and are recommended as test species.

PMID- 16289288
TI  - Volatile organic compounds in selected micro-environments.
AB  - A program of sampling for volatile organic compounds (VOCs) in ambient air was
      undertaken in selected locations and micro-environments in Perth, Western
      Australia to characterise concentrations of target VOCs and to determine the
      relative strength of the contributing sources to ambient air in different micro
      environments in a major Australian city. Twenty-seven locations were sampled and,
      of the forty-one target compounds, 26 VOCs were detected in the samples
      collected. The highest concentrations were recorded for benzene, toluene,
      ethylbenzene, xylenes (BTEX), chloroform and styrene. The maximum 12-h toluene
      and benzene concentrations observed were from a basement carpark and were 24.7
      parts per billion (ppb) and 5.6 ppb, respectively. The maximum xylenes
      concentration was 29.4 ppb and occurred in a nightclub where styrene was also
      detected. A factor analysis of the data was undertaken. Two key factors emerge
      that appear to be associated with petroleum and motor vehicles and environmental
      tobacco smoke. A third significant occurrence was a high concentration of
      chloroform that was observed at a sports centre complex with a swimming pool text
      and was uncorrelated with other compounds in the data set. This study indicates
      that locations associated with motor vehicles and petrol fuel, tobacco and wood
      smoke and chlorinated water represent the major risks for personal exposure to
      VOCs in Perth.

PMID- 16289289
TI  - Accumulation profiles of persistent organochlorines in liver and fat tissues of
      various waterbird species from Greece.
AB  - Waterbirds are particularly subject to accumulation of persistent organic
      pollutants (POPs) that have been shown to constitute a major hazard for this
      group of birds. Liver and fat tissue from ten species belonging to the orders
      Ciconiformes (Ardeidae, Ciconiidae, Phoenicopteridae) and Pelicaniformes
      (Pelecanidae, Phalacrocoracidae) were used as bioindicators in order to assess
      environmental pollution by POPs (HCHs, DDTs, cyclodienes, PCBs) in Greek
      wetlands. To our knowledge, this is the first study on POPs in livers of water
      birds in Greece and Eastern Mediterranean area. The DDTs consisted mainly of p,p'
      DDE with percentages over 60% in the great majority of the samples. The highest
      summation SigmaDDT concentrations were measured in the liver and subcutaneous fat
      of Phoenicopterus rubber and in Ardea purpurea liver (15565, 24706 and 10406 ng
      g(-1) wet weight, respectively). Low concentrations of cyclodienes (Cycls) and
      HCHs were detected occasionally and the contamination pattern of OCPs in most
      species of waterbirds followed the order summation SigmaDDTs> summation
      SigmaCycls> summation SigmaHCHs. Individual values of total PCBs reached the
      levels of 4468 and 3252 ng g(-1) wet weight, for Nycticorax nycticorax and
      Egretta garzetta samples respectively. Some of the recorded differences in
      organochlorine concentrations could be due to different causes of death, with a
      subsequent effect on body lipid levels. Organochlorine pesticides and PCBs
      residues were lower than those commonly associated with mortality and reduced
      reproductive success in most species. However, low level exposure to these
      contaminants may constitute one of the many stressors that in combination could
      adversely affect bird populations.

PMID- 16289290
TI  - Aerobic granulation for organic carbon and nitrogen removal in alternating
      aerobic-anaerobic sequencing batch reactor.
AB  - Microbial granules with excellent settle-ability were successfully developed at
      different ammonium-N loadings in four sequencing batch reactors run under
      alternating aerobic-anaerobic conditions. Results showed that heterotrophic,
      nitrifying and denitrifying populations could co-exist in the microbial granules.
      The activity of denitrifying bacteria was highly determined by the availability
      of external carbon source in the anaerobic phase. Complete denitrification was
      achieved with supply of external carbon source, whereas only partial
      denitrification occurred with no addition of external carbon source. This study
      shows that microbial granules cultivated under the alternating aerobic-anaerobic
      condition could efficiently remove organic carbon and completely convert ammonia
      to nitrogen gas. A new generation of microbial granules-based bioreactor for
      organics and nitrogen removal can be envisaged.

PMID- 16289291
TI  - Characterization and expression sites of newly identified chicken collectins.
AB  - Collectins are members of the family of vertebrate C-type lectins. They have been
      found almost exclusively in mammals, with the exception of chicken MBL. Because
      of their important role in innate immunity, we sought to identify other
      collectins in chicken. Using the amino acid sequences of known collectins, the
      EST database was searched and related to the chicken genome. Three chicken
      collectins were found and designated chicken Collectin 1 (cCL-1), chicken
      Collectin 2 (cCL-2), and chicken Collectin 3 (cCL-3), which resemble the
      mammalian proteins Collectin Liver 1, Collectin 11 and Collectin Placenta 1,
      respectively. Additionally, a lectin was found which resembled Surfactant Protein
      A, but lacked the collagen domain. Therefore, it was named chicken Lung Lectin
      (cLL). Tissue distribution analysis showed cCL-1, cCL-2 and cCL-3 are expressed
      in a wide range of tissues throughout the digestive, the reproductive and the
      lymphatic system. Similar to SP-A, cLL is mainly localized in lung tissue.
      Phylogenetic analysis indicates that cCL-1, cCL-2 and cCL-3 represent new
      subgroups within the collectin family. The newly found collectins may have an
      important function in avian host defence. Elucidation of the role of these
      pattern-recognition molecules could lead to strategies that thwart infectious
      diseases in poultry, which could also be beneficial for public health.

PMID- 16289292
TI  - Apigenin induces apoptosis in Hep G2 cells: possible role of TNF-alpha and IFN
      gamma.
AB  - Flavonoids are one of the biologically active plant food constituents, possessing
      potential chemopreventive properties against a wide variety of chronic diseases.
      Apigenin, a common dietary flavonoid abundantly present in fruits and vegetables
      is believed to possess preventive and therapeutic potential against various
      cancers. In the present study, we have evaluated regulation of apoptotic cell
      death by apigenin (25 and 50 microM) in human hepatoblastoma derived cell line
      Hep G2. Apigenin-induced programme cell death in terms of TNF-alpha, IFN-gamma
      release and induction of caspases activity. TNF-alpha and IFN-gamma levels in
      apigenin-pretreated groups were significantly and dose dependently elevated as
      compared to the control values (28-39% and 66-85%), (208-336% and 579-1088%),
      respectively. Treatment of apigenin significantly induced caspase-3, -7, -10 and
      caspase-9 activity (160-209% and 203-270%) in a dose-dependent manner. The
      effects on caspases, TNF-alpha, and IFN-gamma processes mediate the plausible
      mechanism of apoptosis induction of apigenin.

PMID- 16289294
TI  - Synthesis, characterization and biological activity of lanthanum(III) complexes
      containing 2-methylene-1,10-phenanthroline units bridged by aliphatic diamines.
AB  - Two novel lanthanum(III) complexes containing 2-methylene-1,10-phenanthroline
      units bridged by aliphatic diamines were synthesized and characterized by
      elemental analysis, IR, NMR, thermal analysis and conductance measurements. They
      have been assayed for anticancer activity in vitro against HL-60 (human
      leukocytoma) cells, PC-3MIE8 (human prostate carcinoma) cells, BGC-823 (human
      stomach carcinoma) cells, MDA-MB-435 (human galactophore carcinoma) cells, Bel
      7402 (human liver carcinoma) cells, and Hela (human cervix carcinoma) cells. The
      results show that the two complexes exhibit good cytotoxic activities against
      different cell lines in general, especially more effective than cisplatin against
      Bel-7402, BGC-823 and MDA-MB-435 cell lines. DNA-binding studies indicate that,
      besides the intercalation, the complexes bind to DNA by the other interaction(s),
      which might be responsible for the production of more compact DNA, coinciding
      with more A-like feature of DNA as suggested by CD spectra.

PMID- 16289293
TI  - Paraoxon-induced ultrastructural growth changes of rat cultured hippocampal cells
      in neurobasal/B27.
AB  - Organophosphates (OPs) neurotoxicity is attributed both to their well-known
      cholinergic and recently attended non-cholinergic effects. Since parathion has
      been observed to be responsible for more cases of poisoning than any other OP
      insecticides, it is vitally important to investigate other mechanisms, besides
      cholinesterase inhibition, which can potentially contribute to the neurotoxicity
      of parathion (or its metabolite, paraoxon). In present study, hippocampal cells
      obtained from Wistar rat neonates were cultured in neurobasal medium supplemented
      with B27 serum where different doses of paraoxon were also introduced. The
      neuronal growth in the control group and those exposed to paraoxon was compared.
      Phase contrast microscopy, cell staining (Neutral Red) and computer assessment
      morphometric study (Motic) were used to study cell morphology, viability and type
      of cell death. Statistical analysis was carried out using one-way ANOVA. There
      was no clear morphologic differences between neurons in the control group and
      those exposed to 10 microM paraoxon; however, deformity of the soma was clear in
      pellets containing higher concentration of paraoxon. Ultrastructure of cells was
      markedly altered at 50 microM dose of paraoxon as evidenced by gradual
      discontinuation of cytoplasm, appearing of numerous vacuoles and intracytoplasmic
      myelin figure. The processes (neurites) did not grow in media containing 100
      microM paraoxon or more. Viability decreased with increasing paraoxon especially
      above 100 microM. In conclusion, the present data reveal that paraoxon, in 30
      microM or higher concentrations, induces a decrease in cell growth, followed by
      cell swelling and neuronal death (possibly necrosis).

PMID- 16289295
TI  - Mucilage impact on gorgonians in the Tyrrhenian sea.
AB  - The mucilage phenomenon has affected the Tuscan Archipelago since its first
      appearance (1991) in the Tyrrhenian Sea (Mediterranean Sea) [Innamorati M, Raddi
      E, Buzzichelli A, Melley S, Demoulin M. Le mucillaggini nel Mar Tirreno. Biol Mar
      Suppl Notiz 1992;1:23-26; Sartoni G, Sonni C. Tribonema marinum J. Feldmann e
      Acinetospora crinita (Carmichael) Sauvageau nelle formazioni mucillaginose
      bentoniche osservate sulle coste toscane nell'estate 1991. Inf Bot Ital
      1991;23:23-30; Sartoni G, Cinelli F, Boddi S. Ruolo di Tribonema marinum J.
      Feldmann ed Acinetospora crinita (Carmichael) Sauvageau negli aggregati
      mucillaginosi bentonici delle coste toscane. Biol Mar Suppl Notiz 1993;1:31-34].
      Seasonally, these mucous aggregates become very common in the benthic domain. The
      gorgonians are the most exposed organisms because they provide the best support
      for mucilage growth; indeed, their long branches positioned in orthogonally with
      respect to the current so as to capture plankton, also trap the filamentous
      mucilage present in the water. A 3-year monitoring programme at Capo Calvo
      (Island of Elba) was carried out in order to study the appearance of the mucilage
      phenomenon and its impact on three species of gorgonians (Eunicella cavolinii,
      Eunicella singularis, and Paramuricea clavata). The composition of mucilage and
      the gorgonian recovery capacity, when damaged, were investigated. During the
      first year of study (1999), no relevant interactions between gorgonians and
      mucilages were recorded. Instead, massive presence of mucilages causing different
      types of damage to the different gorgonian species investigated was recorded
      during the second (2000) and third year (2001). The type and the extent of the
      impact of mucilages also depend on the season. Three species of algae
      (Nematochrysopsis marina, Chrysonephos lewisii and Acinetospora crinita)
      constitute the principal components of the mucilaginous aggregates. In general,
      the first two species occur during the spring season, down to 20 m, while A.
      crinita occurs at greater depths. In July, when the mucilages reach their maximum
      development, C. lewisii is the predominant species. This species mainly affects
      E. cavolinii and E. singularis while A. crinita mainly affects P. clavata, which
      colonizes greater depths.

PMID- 16289296
TI  - Relevance of the dinoflagellate Gonyaulax fragilis in mucilage formations of the
      Adriatic Sea.
AB  - Oceanographic cruises were carried out monthly from June 1999 to July 2002 to
      follow the mucilage formation process in the Northern Adriatic Sea. Results show
      that in correspondence with these events the dinoflagellate Gonyaulax fragilis
      (Schutt) Kofoid was observed both in the water column and within mucilage
      aggregates. In the water column, increasing abundances were observed from May
      until July, with values never exceeding 8500 cells l(-1). Much higher densities
      were observed within superficial gelatinous aggregates (22800-3400000 cells l(
      1)). In mucilage samples, a large number of decomposing cells were present,
      together with abundant alive cells, enveloped in exudates. G. fragilis isolated
      from mucilage samples was cultured in three different culture media; it was
      characterized by a low growth rate but it produced a high amount of
      polysaccharides. The highest yield both in terms of cell number and carbohydrate
      production was observed in the medium having the highest nitrogen and phosphorus
      content and the lowest N/P ratio. The monomeric composition of G. fragilis
      carbohydrates, compared with that of mucilage samples, showed that in both
      natural and cultured samples galactose was the most abundant sugar; in addition,
      an overall good correlation, especially between the monomeric carbohydrate
      composition of G. fragilis grown in f/2 medium and that of a mucilage sample in
      which this species was present in high density, was observed.

PMID- 16289297
TI  - Mercury emissions from coal-fired power stations: The current state of the art in
      the Netherlands.
AB  - About 30% of the electricity produced in the Netherlands is generated by coal,
      all of which is imported. At the same time, the co-combustion of biomass is
      becoming increasingly important. For the last 25 years, the fate of the
      elements/trace elements in general and of mercury in particular has been studied
      in great detail. It appears that on average 50% of the mercury is removed in the
      ESP (particulate control) and 50% of the remainder is removed in the flue gas
      desulphurization (FGD), resulting in a total mercury removal of 75%. If a high
      dust selective catalytic reduction (SCR for NO(x) reduction) is present, the
      total removal can be up to 90%. The results indicate that on average the removal
      of mercury during the co-combustion of biomass is similar to that found for full
      coal-firing. The conclusion is that a modern coal-fired power station with the
      above-mentioned flue gas cleaning equipment also removes mercury up to 90%. These
      cleaning devices are being installed to reduce the emission of particulates,
      sulphur dioxide and nitrogen oxides. This means that mercury abatement can be
      increased while meeting the EU regulation for SO(2) and NO(x). The application of
      Best Available Technique (BAT) for coal-fired installations by 1-1-2008 will lead
      to a further increase in the construction and operation of FGD and DeNO(x)
      installations.

PMID- 16289298
TI  - Elevated blood selenium levels in the Brazilian Amazon.
AB  - Contaminated fish poses a difficult challenge throughout the world, on the one
      hand, fish is a very nutritious food source, while on the other hand it
      accumulates many toxic substances, including mercury (Hg). As part of our efforts
      in the Brazilian Amazon to maximize nutritional input from fish consumption, a
      dietary mainstay, and minimize toxic risk, we have been studying the role of
      selenium (Se), an essential element, that may influence the distribution of Hg in
      the body and influence Hg neurotoxicity. Se, which is naturally present in the
      soil, is ingested through consumption of various foods, notably fish, mammals and
      certain plants. The objectives of the present study were: (i) evaluate whole
      blood Se (B-Se) and Hg (B-Hg); (ii) characterize B-Se variations with respect to
      socio-demographic and dietary variables; and (iii) examine the relation between B
      Se and B-Hg. A total of 236 persons from six riparian communities of the Tapajos
      River Basin, a tributary of the Amazon, participated in this study. Whole blood
      Se and Hg were measured and interview administered questionnaires were used to
      obtain data on socio-demographic variable, smoking and drinking habits, and fish
      and fruit consumption. The results show that B-Se are in the upper normal range
      (median=284.3 microg/L, range=142.1-2029.3 microg/L). No individuals presented B
      Se deficiency, but 9 participants from the same extended family had relatively
      high B-Se levels, potentially a threat to their health. B-Se varied between
      communities, was significantly higher among alcohol drinkers and farmers, but not
      associated with age, sex or tobacco consumption. A significant positive relation
      between B-Se and B-Hg was noted, independently of the overall fish consumption. B
      Se increased with consumption of Peacock bass (Cichla sp.), a piscivorous fish
      species, and coconut pulp (Cocos nucifera L.). The B-Se intercommunity variations
      may reflect geographic differences in local soil Se levels as well as traditional
      land use practices in the different ecosystems of the Tapajos River Basin. In
      this population with relatively high exposure to Hg, Se may play an important
      role. Further studies should examine, in this region, the sources of Se, its
      transmission through the terrestrial and aquatic ecosystem and its role with
      respect to human health.

PMID- 16289299
TI  - Spectroscopic evidence of the marine origin of mucilages in the Northern Adriatic
      Sea.
AB  - Vibrational Fourier transform infrared (FTIR) and UV-Visible spectroscopies
      coupled to thermogravimetry were used to characterise the gelatinous aggregates
      as well as the humin and humic fractions extracted from the aggregates.
      Spectroscopic analysis made it possible to identify the main classes of compounds
      present in the samples. The FTIR spectra of the aggregates showed the presence of
      carbohydrates, saturated aliphatic compounds, aminic, esteric, amidic (proteins)
      and ketonic compounds, organic and inorganic phosphates, silica and, in some
      cases, carbonates. The FTIR spectra of humin and humic acids showed functional
      groups similar to those found in the spectra of the aggregates. The high
      aliphatic character and the absence of aromatic compounds observed in many
      aggregates sampled far from estuarine areas suggest the marine origin of
      mucilages. These results were also confirmed by the 270/407 nm (A2/A4) and
      465/665 nm (E4/E6) absorbance ratio in humic acids.

PMID- 16289300
TI  - Behaviour of Hg species in a microtidal deltaic system: the Isonzo River mouth
      (northern Adriatic Sea).
AB  - Mercury species in the highly stratified water column of the Isonzo River mouth
      (northern Adriatic Sea) were investigated in February, May and August 2002 (low
      normal fluvial discharge). Total, dissolved and particulate mercury (Hg) and
      methylmercury (MeHg) were measured and their concentrations were related to
      physico-chemical parameters in terms of temperature, salinity, turbidity, O(2)
      concentrations and total suspended matter (TSM) as well as particulate organic
      carbon (POC) content. Particulate Hg and MeHg are well correlated to medium-fine
      silty suspended sediment and organic matter, respectively. Desorption of Hg from
      particles in the brackish layer was observed. Due to the presence of a saltwedge,
      the lower river course seems to be a trap for Hg carried by fluvial waters. MeHg
      normally decreases approaching the sea but the local increase in the inner zone
      of the saltwedge could be related to methylation processes in the bottom water
      layer. Hg export is effective only during medium and high riverine flows acting
      as an important source of Hg into the northern Adriatic and the adjacent lagoon
      system.

PMID- 16289301
TI  - A comparison of the dietary and total intake of micronutrients in a group of
      pregnant Greek women with the Dietary Reference Intakes.
AB  - OBJECTIVE: We compared the dietary and total (diet and supplement) intake of
      micronutrients with the Dietary Reference Intakes (DRIs) from the USA in a
      population of pregnant Greek women. METHODS: Two hundred pregnant women
      participated in a nutritional survey, 98 in the second trimester and 102 in the
      third trimester in a random sampling. To examine dietary intake we used two
      questionnaires, the nutritional questionnaire for pregnant women from the
      California Department of Health Services, and a semi-quantitative questionnaire
      (Walter Willet) with modifications for use in Greece. Dietary intake analysis was
      performed using the Diet Analysis Plus software, Version 3, ESHA Research.
      Statistical analysis was performed with Minitab for Windows, Release 12. A simple
      complementary questionnaire concerning demographic and socio-economic features
      was also completed. RESULTS: The average total intake of vitamins A, B(1), B(2),
      B(3), B(6), B(12) and C, calcium and phosphorus was higher than the respective
      DRIs. Folic acid and iron intake exceed the highest values specified for
      pregnancy. Vitamin E and zinc was lower than the DRIs, while vitamin D, magnesium
      and thiamin did not differ. CONCLUSIONS: The results of our study suggest that in
      a Greek population, sufficient micronutrients appear to be received in adequate
      amount from diet, except for folic acid and iron, which also had to be taken in
      the form of nutritional supplements.

PMID- 16289302
TI  - The association of endometriosis risk and genetic polymorphisms involving dioxin
      detoxification enzymes: a systematic review.
AB  - Genetic polymorphisms involving genes encoding for dioxin detoxification enzymes
      have been implicated as a risk factor for endometriosis, but individual studies
      have been equivocal and controversial. We therefore performed a systematic review
      of 10 studies on association of endometriosis and various genes involved in
      dioxin detoxification process excluding GSTM1/GSTT1. We found that almost all
      genetic variants involving CYP1A1, CYP2E1, EPHX1, AHR, ARNT, AHRR, and NAT1 that
      have been investigated by single studies show no association with endometriosis.
      Two genetic variants were reported to be associated with endometriosis, with each
      variant only investigated by a single study and there has been no independent
      confirmation so far. For CYP1A1 MspI polymorphisms, women with +/- and +/+
      genotype have about 40% of increased risk of endometriosis as compared with women
      of -/- genotype. However, there is no strong indication that CYP1A1 MspI
      polymorphism is consistently associated with endometriosis. For NAT2
      polymorphisms, there is no evidence that it is associated with endometriosis.

PMID- 16289303
TI  - The emergence of infections with community-associated methicillin resistant
      Staphylococcus aureus.
AB  - Recently there have been reports indicating an increased incidence of MRSA
      infections, afflicting individuals with no apparent risk factors for hospital
      acquisition. Patients with community-associated (CA) MRSA are significantly
      younger and had different distributions of clinical infections compared with HA
      MRSA patients. CA-MRSA infections have mostly been associated with staphylococcal
      strains bearing the SCCmec type IV element and PVL genes. These strains are more
      frequently susceptible to a variety of non-beta-lactam antibiotics. Clinicians
      must be aware of the wide and, in some cases, unique spectrum of disease caused
      by CA-MRSA. Continued emergence of MRSA in the community is a public-health
      problem that warrants increased vigilance in the diagnosis and management of
      suspected and confirmed staphylococcal infections.

PMID- 16289304
TI  - Differences between the growth regulatory pathways in primary rat adrenal cells
      and mouse tumor cell line.
AB  - In this study, DNA synthesis, phosphorylation of ERK1/2 and CREB proteins, as
      well as induction of c-Fos protein, were examined in rat adrenocortical,
      glomerulosa and fasciculata/reticularis cells, as well as in the Y1 cell line. We
      found that FGF2 was mitogenic only in glomerulosa cells and although ACTH did not
      activate ERK1/2, it did activate CREB protein, indicating efficient transduction
      of signals initiated in the ACTH receptors of rat adrenocortical cells. The FGF2
      activated ERK1/2 in rat adrenal cells by a mechanism that might be modulated by
      upstream PKA pathway phosphorylation of MEK and despite the nonmitogenic effect
      of ACTH on rat adrenal cells it effectively induces c-Fos protein. The results
      presented herein describe distinct differences between the ACTH and FGF2 signal
      transduction mechanisms seen in adrenocortical cells and those observed in the Y1
      cell line, indicating that, in vitro, ACTH blockage of the mitogenic effect
      occurs in normal adrenal cells after induction of c-Fos protein.

PMID- 16289305
TI  - Modulation of iodide uptake by dialkyl phthalate plasticisers in FRTL-5 rat
      thyroid follicular cells.
AB  - Plasticisers imparting flexibility to plastics are man-made chemicals abundantly
      present in the environment. Effects of six different dialkyl phthalates were
      studied in vitro in the rat thyroid cell line FRTL-5 on their ability to modulate
      basal iodide uptake mediated by the sodium/iodide symporter (NIS). The present
      study shows that diisodecyl phthalate (DIDP), dioctyl phthalate (DOP), diisononyl
      phthalate (DINP) and bis (2-ethylhexyl) phthalate (DEHP) significantly enhance
      iodide uptake when concentrations in the magnitude between 10(-4) M and 10(-3) M
      were applied. In this range, these phthalates do not assess toxicity on the
      cells. Specific inhibiton of NIS demonstrated that enhancement of iodide uptake
      is due to NIS. In contrast, benzyl butyl phthalate (BBP) also augments iodide
      uptake at 1mM but this concentration has just exceeded the toxicity threshold and
      dibutyl phthalate (DBP), the most toxic compound did not modulate iodide uptake
      at any concentration applied. As we can deduce from our results, plasticisers are
      capable of significantly modulating NIS mediated iodide uptake activity.

PMID- 16289307
TI  - Gene regulation profiles by progesterone and dexamethasone in human endometrial
      cancer Ishikawa H cells.
AB  - OBJECTIVE: Progesterone and glucocorticoids such as dexamethasone mediate
      distinct biological functions, yet they bind to receptors that recognize the same
      consensus DNA response element. In breast cancer, progestins are associated with
      the incidence and progression of tumors, whereas glucocorticoids are growth
      suppressive in mammary cancer cells; the differential effects of these two
      steroids are less well understood in the hormone-dependent disease cancer of the
      uterine endometrium. We set out to identify genes that are regulated by
      progesterone through progesterone receptors and dexamethasone through
      glucocorticoid receptors in a well-differentiated human endometrial cancer cell
      line. METHODS: PR- and GR-positive Ishikawa H endometrial cancer cells were
      treated with vehicle, dexamethasone (100 nM) or progesterone (100 nM) for 2 h, 6
      h, 12 h and 24 h, and RNA was isolated. Affymetrix microarrays were performed
      using the human HG-U133A chip, querying the expression of 22,000 genes.
      Expression of genes of particular interest was confirmed by real-time RT-PCR.
      RESULTS: Expression analysis demonstrated that dexamethasone and progesterone
      regulate overlapping but distinct sets of genes and presumably exert many similar
      but also unique biological effects. Using real-time RT-PCR, we confirmed three
      particular genes of interest: the transcript for cysteine 1 (legumain), a gene
      associated with metastasis, that is strongly downregulated by progesterone,
      upstream c-fos relating transcription factor-2 (USF-2), an anti-proliferative
      factor that is induced by both progesterone and dexamethasone and N-cadherin, a
      cellular adhesion molecule downregulated by dexamethasone. CONCLUSION: These
      studies provide new insight into the effects of progesterone and dexamethasone in
      endometrial cancer cells and provide an extensive list of regulated pathways
      which can be assessed in the future as biomarkers and molecular targets for new
      therapies. Taken together, our findings indicate that progesterone and
      dexamethasone are primarily growth inhibitors in Ishikawa H endometrial cancer
      cells.

PMID- 16289308
TI  - Orphan GPCRs and their ligands.
AB  - Due to their diversity, G-protein-coupled receptors (GPCRs) are major regulators
      of intercellular interactions. They exert their actions by being activated by a
      vast array of natural ligands, referred to in this article as "transmitters". Yet
      each GPCR is highly selective in its ligand recognition. Traditionally, the
      transmitters were found first and served to characterize the receptors
      pharmacologically. Since the end of the 1980s, however, it is the GPCRs that are
      first to be found because they are identified molecularly by homology screening
      approaches. But the GPCRs found this way suffer of one drawback, they lack their
      natural transmitters, they are "orphan" GPCRs. Searching for transmitters of
      orphan GPCRs has given birth to the reverse pharmacology approach that uses
      orphan GPCRs as targets to identify their transmitters. The most salient
      successes of the reverse pharmacology approach were the discoveries of 9 novel
      neuropeptide families. These have enriched our understanding of several important
      behavioral responses. But the application of reverse pharmacology has also led to
      some surprising results that question some basic pharmacological concepts. This
      review aims at describing the history of the orphan GPCRs and their impact on our
      understanding of biology.

PMID- 16289309
TI  - Thrombolytic therapy in acute ischemic stroke in Asia: The first prospective
      evaluation.
AB  - OBJECTIVE: Intravenous thrombolytic therapy has been widely recommended as a
      standard treatment for acute ischemic stroke in most clinical practice
      guidelines. However, the experience in Asia is still limited. We report the first
      prospective case series of thrombolytic therapy in a developing Asian country.
      PATIENTS AND METHODS: Consecutive patients with acute ischemic stroke who
      presented within 3 h of onset were screened under stroke fast track program.
      Those who were eligible were treated with intravenous recombinant tissue
      plasminogen activator (rt-PA). General and neurological examinations together
      with the National Institute of Health stroke scale (NHISS) and modified Rankin
      scale (MRS) were recorded prior to and after the treatment at 1 h, 24 h, on
      discharge and at 3 months. Hemorrhagic brain lesion and death within 3 months
      were also recorded. RESULTS: Thirty-four patients or 2.1% of patients with acute
      stroke received intravenous thrombolysis. The mean pretreatment NIHSS was 18.8
      and the majority of patients had stroke in the middle cerebral artery territory.
      The mean door-to-needle time was 72.6 min (ranged 20-150 min). Major neurological
      improvement, defined as improving of the NIHSS >8 points or NIHSS of 0 points at
      24 h, was observed in 17 patients (50%). Intracerebral hemorrhage was detected in
      four cases (11.8%), two of them were symptomatic (5.9%) and one was fatal.
      CONCLUSION: Intravenous thrombolysis can be given in patients with acute stroke
      in our population. Our cases were more severe than other studies. However, half
      of them experienced major neurological improvement. The risk of hemorrhagic brain
      lesion is not much higher than previously reported.

PMID- 16289310
TI  - Symptomatic and asymptomatic abnormalities in patients with lumbosacral radicular
      syndrome: Clinical examination compared with MRI.
AB  - OBJECTIVE: To determine the frequency of symptomatic and asymptomatic herniated
      discs and root compression in patients with lumbosacral radicular syndrome (LRS)
      and to correlate clinical localization with MRI findings. METHODS: Fifty-seven
      patients with unilateral LRS were included in the study. Using the visual
      analogue scale, two physicians independently localized the most likely lumbar
      level of complaints. These clinical predictions of localizations were correlated
      with the MRI findings. RESULTS: MRI showed abnormalities on the symptomatic side
      in 42 of 57 patients (74%). In 30% of the patients, MRI confirmed an abnormality
      at the exact same level as determined after clinical examination. On the
      asymptomatic side, MRI showed abnormalities in 19 of 57 patients (33%), 13 (23%)
      of these patients had asymptomatic root compression. CONCLUSIONS: In more than
      two-thirds of the patients with unilateral LRS there was no exact match between
      the level predicted by clinical examination and MRI findings. These discrepancies
      complicate the decision whether or not to operate.

PMID- 16289311
TI  - Glucocorticoid regulation of peptide genes in neuroendocrine CRH neurons: a
      complexity beyond negative feedback.
AB  - This review will examine our current knowledge of a fundamental property of CRH
      neuroendocrine neurons: how the major endpoint of the HPA axis--adrenal
      glucocorticoids--interacts with the mechanisms controlling the expression of the
      genes that encode ACTH secretogogues. A great deal of work over the past 25 years
      has led to the notion that this question has an ostensibly simple answer:
      glucocorticoids inhibit peptide gene expression using "negative feedback" at the
      CRH neuron and elsewhere. However, closely examining how glucocorticoids act in
      different physiological circumstances reveals a much more complex set of answers,
      particularly if we consider how the processes that control peptide synthesis and
      release are coupled. Out of this examination emerges a more flexible and complex
      framework for examining the integrative mechanisms controlling the CRH neuron.
      Although we will mostly focus on the Crh gene, relevant aspects of the
      vasopressin (Avp) and pro-enkephalin (pEnk) gene regulatory mechanisms will also
      be discussed.

PMID- 16289312
TI  - Biogenesis, molecular regulation and function of plant isoprenoids.
AB  - Isoprenoids represent the oldest class of known low molecular-mass natural
      products synthesized by plants. Their biogenesis in plastids, mitochondria and
      the endoplasmic reticulum-cytosol proceed invariably from the C5 building blocks,
      isopentenyl diphosphate and/or dimethylallyl diphosphate according to complex and
      reiterated mechanisms. Compounds derived from the pathway exhibit a diverse
      spectrum of biological functions. This review centers on advances obtained in the
      field based on combined use of biochemical, molecular biology and genetic
      approaches. The function and evolutionary implications of this metabolism are
      discussed in relation with seminal informations gathered from distantly but
      related organisms.

PMID- 16289313
TI  - Beta-2 adrenergic receptor gene (ADRB2) polymorphism and risk for lung
      adenocarcinoma: a case-control study in a Chinese population.
AB  - The incidence of lung adenocarcinoma (AC) has been increasing over recent
      decades. The tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) is one of the most potent carcinogens and reproducibly induces a high
      incidence of lung AC in laboratory animals. In addition to its genotoxic effects,
      NNK has also epigenetic effects on lung cells by functioning as an agonist for
      beta adrenergic receptors and stimulating the signal pathways that lead to lung
      AC. Beta-2 adrenergic receptor (ADRB2) expressed on bronchial smooth muscle is a
      well-defined target for asthma treatment that has epidemiological implications in
      lung cancer development. And biochemical effect and pharmacogenetic relevance of
      regulatory and coding variants of ADRB2 have been well documented. Aiming to test
      whether the genetic variants of ADRB2 modify risk of lung AC, we compared the
      manifestation of three common single nucleotide polymorphisms (SNPs) of ADRB2 (G
      1023A, G-654A, and A46G (Gly16Arg)) between 313 patients with lung AC and 321
      controls. Overall association was not observed between risk and either individual
      of the three SNPs or their combined haplotypes. However, in the subgroup of young
      subjects < or =50 years old, significant association was observed for G-1023A
      (allele based OR, 1.82; 95% CI, 1.12-2.95), A46G (Gly16Arg) (allele based OR,
      0.64; 95% CI, 0.40-1.03), and the haplotype A(-1023)A(46) (OR 2.62; 95% CI 1.30
      5.27). Our results do not support a major independent role of ADRB2 polymorphisms
      in lung AC risk, suggesting that functional variants of other genes involved in
      the NNK epigenetic pathway of carcinogenesis should be investigated.

PMID- 16289314
TI  - Lack of sustainable prevention effect of the "Smoke-Free Class Competition" on
      German pupils.
AB  - BACKGROUND: This study examines the effectiveness of the school-based campaign
      "Smoke-Free Class Competition" as a means of preventing young non-smokers from
      taking up smoking. METHODS: Based on two measurements of the Heidelberg
      Children's Panel Study (1998 and 2000), a longitudinal sample of 1704 pupils was
      examined: 948 in the intervention group and 756 in the control group. In order to
      evaluate the effects of the intervention, we compared the smoking behavior in the
      intervention and the control group at two points in time, shortly before, and 18
      months after the intervention, on an individual case basis. RESULTS: (1)
      Stabilization of never-smoking rates: the proportion of pupils remaining a never
      smoker at the follow-up is 62.1% in the intervention group and 61.5% in the
      control group (OR 1.02, 95% CI: 0.83-1.24); (2) Lowering of relapse rates among
      ex-smokers: the proportion of former smokers who had not started smoking again in
      the follow-up is 45.1% in the intervention group and 41.4% in the control group
      (OR 1.07, 95% CI: 0.77-1.49). CONCLUSION: The "Smoke-Free Class Competition" did
      not prevent smoking among adolescents and does not appear to be an effective
      substitute to the complete ban of tobacco advertising, the abolition of vending
      machines and the creation of smoke-free environments in German schools.

PMID- 16289315
TI  - Custom-designed high-density conformal planar multielectrode arrays for brain
      slice electrophysiology.
AB  - Multielectrode arrays have enabled electrophysiological experiments exploring
      spatio-temporal dynamics previously unattainable with single electrode
      recordings. The finite number of electrodes in planar MEAs (pMEAs), however,
      imposes a trade-off between the spatial resolution and the recording area. This
      limitation was circumvented in this paper through the custom design of experiment
      specific tissue-conformal high-density pMEAs (cMEAs). Four configurations were
      presented as examples of cMEAs designed for specific stimulation and recording
      experiments in acute hippocampal slices. These cMEAs conformed in designs to the
      slice cytoarchitecture whereas their high-density provided high spatial
      resolution for selective stimulation of afferent pathways and current source
      density (CSD) analysis. The cMEAs have 50 or 60 microm center-to-center inter
      electrode distances and were manufactured on glass substrates by
      photolithographically defining ITO leads, insulating them with silicon nitride
      and SU-8 2000 epoxy-based photoresist and coating the etched electrode tips with
      gold or platinum. The ability of these cMEAs to stimulate and record
      electrophysiological activity was demonstrated by recording monosynaptic,
      disynaptic, and trisynaptic field potentials. The conformal designs also
      facilitated the selection of the optimal electrode locations for stimulation of
      specific afferent pathways (Schaffer collaterals; medial versus lateral perforant
      path) and recording the corresponding responses. In addition, the high-density of
      the arrays enabled CSD analysis of laminar profiles obtained through sequential
      stimulation along the CA1 pyramidal tree.

PMID- 16289316
TI  - COX-2 expression in the guinea pig cochlea is partly altered by moderate sound
      exposure.
AB  - The cyclooxygenase-2 isoform (COX-2) was found recently to be constitutively
      expressed in the guinea pig inner ear. To gain knowledge about its role in sound
      perception, alterations in the COX-2 level of moderate noise-stimulated cochleae
      were determined. Staining intensities were quantified in different regions using
      an immunohistochemical staining procedure and computer-assisted system. After 70
      dB and 90 dB noise exposure for 1 h at 8000 Hz, COX-2 downregulation was observed
      in the organ of Corti, which was most prominent in Deiters' cells near Hensen
      cells and outer hair cells. In pillar cells, COX-2 levels were only slightly
      reduced after 70 dB but strongly diminished after 90 dB exposure. In Hensen
      cells, COX-2 was downregulated after 70 dB stimulation, revealing a decreasing
      COX-2 content from the third to the first turn of the cochlea and a homogeneously
      reduced enzyme expression in all three turns after 90 dB. The COX-2 content in
      inner hair cells was nearly identical to unexposed cochleae after 70 dB exposure
      but significantly reduced after 90 dB stimulation. In spiral ganglion cells,
      stria vascularis, spiral ligament and limbus, COX-2 expression was unchanged
      after 70 dB and 90 dB. We suggest that alterations in COX-2 expression might
      contribute to diminished sensitivity at the cochlea after noise exposure to
      reduce subsequent noise distress, termed sound conditioning.

PMID- 16289317
TI  - Cochlear damage due to germanium-induced mitochondrial dysfunction in guinea
      pigs.
AB  - This investigation addressed the effect of germanium dioxide (GeO(2))-induced
      mitochondrial dysfunction on hearing acuity. Guinea pigs were fed chow that
      contained 0%, 0.15%, or 0.5% GeO(2). The animals that were fed 0.5% GeO(2) for 2
      months developed hearing impairment chiefly due to degeneration of stria
      vascularis and cochlear supporting cells, which exhibited electron-dense
      mitochondrial inclusions. Cytochrome c oxidase activity was decreased in the
      skeletal muscles and kidney, which also exhibited electron-dense mitochondrial
      inclusions. No apparent pathological changes were observed in the utricle,
      semicircular canal, or among the vestibular nerve fibers, or in the liver or
      heart. The untreated animals and those treated with 0.15% GeO(2) did not exhibit
      hearing impairment or pathological changes in any organs. These findings suggest
      that administration of 0.5% GeO(2) induces mitochondrial dysfunction in the stria
      vascularis and supporting cells in the cochlea, as in the skeletal muscles and
      kidney, thereby causing hearing impairment in the guinea pigs.

PMID- 16289318
TI  - 1-Benzyl-1,2,3,4-tetrahydroisoquinoline passes through the blood-brain barrier of
      rat brain: an in vivo microdialysis study.
AB  - Previous work has established that 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1
      BnTIQ) causes a parkinsonian syndrome in rats. The present study reports the
      blood-brain barrier (BBB) permeability of 1-BnTIQ in freely moving rats with the
      aid of in vivo microdialysis-based measurements. The microdialysis probe was
      implanted in the frontal cortex of rat brain. Brain dialysate samples were
      analyzed using an HPLC-MS/MS assay. 1-BnTIQ, when administered i.p., dose
      dependently appeared in brain extracellular fluid (ECF), reaching a maximum
      concentration after about 40 min. Two other tetrahydroisoquinoline derivatives,
      1,2,3,4-tetrahydroisoquinoline (TIQ) and 6,7-dihydroxy-1-methyl-1,2,3,4
      tetrahydroisoquinoline [salsolinol (SAL)], served as positive and negative
      controls, respectively. The results confirmed an earlier report that SAL does not
      reach the brain after i.p. administration. In contrast, TIQ readily passed
      through the BBB. The brain dialysate concentration of 1-BnTIQ was about 24% that
      of TIQ when administered i.p. at the same dose. Both of them decreased quickly
      with a half-life of about 50 min.

PMID- 16289319
TI  - Spatial decisions in rats based on the geometry of computer-generated patterns.
AB  - Animals often demonstrate the ability to use the geometric configuration of
      multiple landmarks for orientation in the environment. We developed a new
      behavioral task using a computer screen for presentation of visual stimuli
      allowing the rats to make navigational decisions in real space according to the
      geometric configuration of external virtual patterns (designed as a possible
      representation of this space). The rats were placed in a Skinner box with four
      nosing holes in the transparent front wall through which the computer screen was
      visible. They were trained in successive phases: first the visual stimulus
      displayed on the screen directly marked the rewarded nosing hole, then the
      displayed stimuli were reduced in size or displaced, thus disconnected from the
      response space. The results suggested that rats were able to use the geometric
      configuration of stimuli presented on the computer screen for navigational
      decisions in real space.

PMID- 16289320
TI  - Acupuncture normalizes the release of accumbal dopamine during the withdrawal
      period and after the ethanol challenge in chronic ethanol-treated rats.
AB  - Many studies have shown that acupuncture can contribute to the biochemical
      balance in the central nervous system and maintenance or recovery of homeostasis.
      It is well known that chronic administration of ethanol may produce depletion or
      sensitization of extracellular dopamine levels in the nucleus accumbens. The
      present study was designed to investigate the effects of acupuncture on chronic
      ethanol-induced changes in extracellular dopamine levels in the nucleus accumbens
      shell (using in vivo microdialysis in unanesthetized rats). Male Sprague-Dawley
      rats were treated with 3 g/kg/day of ethanol (20%, w/v) or saline by
      intraperitoneal injection for 21 days. Following 72 h of ethanol withdrawal,
      acupuncture was applied at bilateral Shenmen (HT7) points for 1 min. Different
      group of rats using the same paradigm of ethanol treatment were acupunctured at
      the same points after the systemic ethanol challenge (3 g/kg, i.p.). Acupuncture
      at the specific acupoint HT7, but not at control points (PC6 or tail)
      significantly prevented both a decrease of extracellular dopamine levels in the
      nucleus accumbens during ethanol withdrawal and an increase in accumbal dopamine
      levels induced by the ethanol challenge. These results provided strong evidence
      that stimulation of the specific acupoint HT7 helps to normalize the release of
      dopamine in the mesolimbic system following chronic ethanol treatment.

PMID- 16289321
TI  - Effect of neonatal body temperature on postanoxic, potentially neurotoxic iron
      accumulation in the rat brain.
AB  - In asphyxiated newborns iron, released from heme and ferritin and deposited in
      the brain, contributes to neurodegeneration. Because hypothermia provides
      neuroprotection, newborn mammals, showing spontaneously reduced body temperature,
      might avoid the iron-mediated neurotoxicity. Therefore, we decided to study the
      effects of body temperature and chelation of iron with deferoxamine on iron
      accumulation in the brain of three weeks old rats exposed neonatally to a
      critical anoxia. At the age of two days, newborn rats were exposed to anoxia in
      100% nitrogen atmosphere. Rectal temperature was kept at 33 degrees C (typical of
      the rat neonates), or elevated to a level typical of febrile (39 degrees C)
      adults. Control rats were exposed to atmospheric air in the respective thermal
      conditions. Half of the rats exposed to anoxia under hyperthermic conditions were
      injected with deferoxamine (DF), immediately after anoxia and 24 h later.
      Regional changes in cerebral iron deposition were examined in the frontal cortex,
      the hippocampus and the striatum, using iron histochemistry, when the rats
      reached the age of three weeks. Increased iron staining was found in neurons of
      each of the three cerebral regions in rats exposed to neonatal anoxia under
      hyperthermic conditions and the iron accumulation was prevented by postanoxic DF
      injection. In conclusion, febrile body temperature amplifies cerebral
      hyperferremia, which might induce neurodegenerative disturbances in the brain. On
      the other hand, a protection against the brain hyperferremia can be achieved by
      both the reduced physiological neonatal body temperature and by postasphyxic DF
      administration.

PMID- 16289322
TI  - Interferon-gamma- and interleukin-4-producing T cells in Down's syndrome.
AB  - Down's syndrome (DS) associates with genetic-dependent dysregulation of the
      interferon (IFN) system. We used intracellular cytokine staining to analyse the
      percentages of IFN-gamma- and interleukin (IL)-4-producing T cells in the
      peripheral blood of patients with DS, individuals with mental retardation (MR),
      and healthy controls (HCs). The percentages of IFN-gamma-producing CD4(+) and
      CD8(+) T cells (IFGCs), namely Th1 (mean, 21.4+/-S.D. 1.3) and Tc1 (12.6+/-1.1),
      and the Th1/Th2 ratio (6.1+/-0.2) in DS were significantly higher than in MR
      (15.9+/-1.3, 7.9+/-0.6, 4.8+/-0.3) and in HCs (15.6+/-1.9, 7.2+/-1.1, 4.6+/-0.6).
      Most of the DS patients with high IFGC percentages were seropositive for anti
      transglutaminase IgA. We found no correlation between sex, age, APOE genotypes,
      coexisting autoimmune diseases, susceptibility to infections, or degree of
      cognitive impairment and high IFGC percentages. This abnormality might thus
      contribute to immune dysfunction in DS without manifest clinical correlates.

PMID- 16289323
TI  - Dopamine, oxytocin, and vasopressin receptor binding in the medial prefrontal
      cortex of monogamous and promiscuous voles.
AB  - Comparisons between monogamous and promiscuous vole species have proven useful in
      examining neurobiological mechanisms underlying social attachment. Reward
      processing is important for social attachment, and the medial prefrontal cortex
      (mPFC) exerts a direct influence on reward pathways. Dopamine (DA), oxytocin
      (OT), and arginine vasopressin (AVP) all have been implicated in the regulation
      of social attachment in monogamous voles. Therefore, we used radiolabeled ligands
      to examine dopamine D(1)- and D(2)-like, OT, and AVP V(1a) receptor binding
      densities in the mPFC of monogamous and promiscuous voles. Species differences
      were found; monogamous voles had higher densities of D(2)-like and OT receptor
      binding and lower densities of D(1)-like and V(1a) receptor binding than did
      promiscuous voles. Sex differences also were found; females had higher densities
      of OT receptor binding but lower densities of V(1a) receptor binding than did
      males in both species. Further, the laminar distribution of receptor binding
      indicates the possibility of an interaction between DA and OT systems in the mPFC
      in the regulation of social attachment. Differences in D(1)- and D(2)-like
      receptor binding between species are discussed in terms of how they might
      modulate cortical activity and subsequent DA release in the nucleus accumbens
      (NAcc).

PMID- 16289325
TI  - Dissecting why superovulation and embryo transfer usually work on some farms but
      not on others.
AB  - Bovine embryo transfer is a well-established commercial industry that is often
      associated with veterinary practices. Practitioners offering embryo transfer
      services may possess a very high standard of technical expertise; however,
      success in the production of embryos and the impregnation of recipients cannot be
      achieved unless the cattle are healthy and maintained in a well-managed cattle
      operation. In addition to appropriate gonadotropin treatments of donor cattle,
      the use of highly fertile semen, known to have been properly stored and handled
      is required for success. Recipient cattle must be managed with the same attention
      to detail as donors. Traditionally, PGF has been used for the synchronization of
      recipients. However, PGF is limited in its effectiveness early and late in the
      bovine estrus cycle. Recipient estrus synchronization with progesterone releasing
      intravaginal inserts has been successful and high pregnancy rates have resulted
      following embryo transfer.

PMID- 16289324
TI  - Interleukin-15 enhances the secretion of IFN-gamma and CC chemokines by natural
      killer cells from HIV viremic and aviremic patients.
AB  - Several lines of evidence documented a renewed interest in the role of natural
      killer (NK) cells in the innate immune control of HIV infection and disease
      progression. To further assess the role of NK cells as target for immunotherapy
      in HIV infection, we evaluated the priming effect of interleukin (IL)-15 on
      freshly isolated human peripheral NK cells, from viremic and aviremic HIV
      infected patients, measuring the production of IFN-gamma and CC chemokines. In
      vitro IL-15 priming induced a significant increase of IFN-gamma production in
      both viremic and aviremic patients. IL-15 stimulated NK cells producing CC
      chemokine quantities that are reported to be capable of inhibiting HIV infection
      and replication. This priming effect is observed both in viral suppressed
      patients after antiretroviral therapy, and in viremic subjects with progressive
      HIV infection. The combination of IL-15 plus IL-12 is the most potent costimulus
      for CD69 expression and production of CC chemokines by NK cells. These findings
      indicate that NK cells are an important target for immunotherapeutic agents and
      provide additional pre-clinical data supporting the great potential of IL-15 in
      the immune-based interventions in HIV disease.

PMID- 16289326
TI  - The Holstein cow in embryo transfer today as compared to 20 years ago.
AB  - Embryo transfer practice and results were examined over a 20-year period in
      Holstein cows and heifers within four commercial embryo transfer programs located
      in different areas of North America. Mean embryo production per collection
      decreased (P < 0.05) in one program over time, but not in the other three.
      Changes in the type of cows entering embryo transfer programs, the number of
      times they were superstimulated and changes in the brands of gonadotropins used
      for superstimulation all complicated the analysis of embryo production over time.
      Data reveal higher pregnancy rates (P < 0.001) following transfer of embryos into
      Holstein heifers than into lactating dairy cows. It is not clear whether
      pregnancy rates have decreased over time as a result of the change from surgical
      to non-surgical embryo transfer. In the two programs in which pregnancy rates
      were analyzed, there was a decrease (P < 0.001) when non-surgical transfers were
      adopted in one program, while no change occurred in the other. One of the biggest
      changes in all programs was that more than 50% of embryos recovered from donors
      are now frozen after collection, whereas the majority were transferred fresh 20
      years ago.

PMID- 16289327
TI  - Disruption of cerebellar granule cell development in the Pax6 mutant, Sey mouse.
AB  - The transcriptional regulator Pax6 is expressed in cerebellar granule cells and a
      mutation in that gene (Sey) has been shown to affect cerebellar development. We
      have defined novel phenotypes in the Sey/Sey cerebellum, indicating that the
      mutation of Pax6 alters granule cell behavior in vitro and also the interaction
      between granule cells and Purkinje cells in vivo. In culture, Sey/Sey granule
      cell precursors show the following abnormal phenotypes: enhanced proliferation,
      increased apoptotic cell death, and decreased number of morphologically
      differentiating beta-III tubulin-positive cells. There is an overlap in the
      populations of Sey/Sey cells that express markers for proliferation and neuronal
      differentiation indicating an abnormality in the transition between these states
      in granule cells. In vivo, Purkinje cell ectopias were found deep in the
      cerebellum and extending into the inferior colliculus. Coincident with this,
      Purkinje cell phenotype was the alteration in the pattern and levels of Reelin
      expression in granule cells of the external germinal layer (EGL). The finding of
      increased staining for Disabled-1, a signaling pathway intermediary that is
      normally downregulated by a Reelin signal, throughout the Purkinje cell
      population suggests that in the Sey/Sey cerebellum there is a disruption in
      Reelin signaling from the EGL to Purkinje cells. These findings suggest that Pax6
      is critical for the proper differentiation of granule cells and their
      communication with developing Purkinje cells. Thus, through its guidance of
      granule cell development, Pax6 also has a strong influence on many of the
      cellular programs that guide the morphogenesis of the entire cerebellum.

PMID- 16289328
TI  - Physical characterization of vascular grafts cultured in a bioreactor.
AB  - Tubular scaffolds of collagen and elastin (weight ratio 1:1) with interconnected
      pores were prepared by freeze drying and crosslinked with N-(3
      dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N
      hydroxysuccinimide (NHS) in the presence or absence of a Jeffamine spacer
      (poly(propylene glycol)-bis-(2-aminopropyl ether), J230). The crosslinked and
      uncrosslinked matrices had porosities of 90% and average pore sizes of 131-151
      microm. Smooth muscle cells (SMC) were cultured in the crosslinked and
      uncrosslinked tubular scaffolds under pulsatile flow conditions (mean flow rate
      9.6 ml/min, 120 beats/min, pressure 80-120 mmHg). All the constructs could
      withstand cyclic mechanical strain in the absence of any mechanical support
      without cracking or suffering permanent deformation. After 7d, SMC were
      homogeneously distributed throughout the uncrosslinked and EDC/NHS crosslinked
      constructs, whereas hardly any cell was observed on the luminal side of
      J230/EDC/NHS crosslinked matrices. Considering the better mechanical performance
      of EDC/NHS crosslinked matrices compared to non-crosslinked constructs after 7d
      of culture, SMC were dynamically cultured in the former scaffolds for 14d. During
      this period, the high strain stiffness of the constructs increased more than two
      fold to 38+/-2 kPa, whereas the low strain stiffness doubled to 8+/-2 kPa. The
      yield stress and yield strain were 30+/-10 kPa and 120+/-20%, respectively. SMC
      were homogeneously distributed throughout the EDC/NHS crosslinked
      collagen/elastin constructs and collagen fibres tended to orient in the
      circumferential direction.

PMID- 16289329
TI  - Use of two in vitro methods for the detection of anthelmintic resistant nematode
      parasites on Slovak sheep farms.
AB  - A survey of the prevalence of anthelmintic resistant nematode populations was
      conducted on 32 sheep farms in the Slovak Republic. In vitro egg hatch test and
      larval development tests were used for the detection of resistance to
      benzimidazole anthelmintics and they were compared with in vivo faecal egg count
      reduction tests. There was agreement in the declaration of resistance between the
      faecal egg count reduction test and both in vitro tests. The presence of
      resistant populations was determined on two farms using egg hatch test. In both
      farms, the LD(50) values were higher than 0.1 microg TBZ/ml, indicating
      resistance. By using LD(99) values it might be possible to reveal relatively
      small proportion of resistant larvae in the population. The prevalence of
      benzimidazole resistance has not change on Slovak sheep farms during last decade.

PMID- 16289330
TI  - Preoperative concentration of beta-lipotropin immunoreactive material in
      cerebrospinal fluid: a predictor of postoperative pain?
AB  - Levels of beta-endorphin immunoreactive material (IRM) in cerebrospinal fluid
      (CSF) have been reported to correlate inversely with postoperative morphine
      requirement. Considering proopiomelanocortin (POMC) derivatives as predictors for
      sensitivity to postoperative pain, we determined authentic beta-endorphin (beta
      endorphin(1-31)), beta-lipotropin IRM, N-acetyl-beta-endorphin IRM and ACTH in
      CSF of 17 patients undergoing hip or knee arthroplasty, before surgery (t(A)),
      immediately after termination of propofol infusion and still under spinal
      anesthesia (t(B)), under postoperative pain (t(C)) and one day after surgery
      (t(D)); patients rated their severity of pain on a visual analogue scale (VAS) at
      those four times. In all patients CSF concentrations of N-acetyl-beta-endorphin
      IRM and beta-lipotropin IRM were found to be increased after terminating the
      propofol infusion with spinal anesthesia still effective at t(B). Patients did
      not feel pain at times t(A), t(B) or t(D); however, they reported moderate to
      considerable pain at t(C). There were no correlations of postoperative pain
      severity at t(C) with ACTH, beta-endorphin(1-31) or N-acetyl-beta-endorphin IRM
      concentrations in CSF. In contrast, we observed significant inverse correlations
      (Spearman's rank correlation coefficients between -0.83 and -0.85, p<0.01) for
      postoperative pain severity with beta-lipotropin IRM concentrations in CSF at
      t(C), and, in addition, at t(A), t(B) and t(D); thus, postoperative pain severity
      appeared to be dependent on a central system controlling sensitivity to pain,
      linked to a POMC system releasing beta-lipotropin IRM into CSF and already active
      at times t(A) and t(B). We conclude that beta-lipotropin IRM in CSF might be
      considered to serve as a predictor of sensitivity to postoperative pain.

PMID- 16289331
TI  - Prolactin induced reversal of glucocorticoid mediated apoptosis of immature
      cortical thymocytes is abrogated by induction of tumor.
AB  - Glucocorticoid (GC) and prolactin (PRL) are the two neuroendocrines that regulate
      thymocyte differentiation and maintain the immune homeostasis during stress. We
      found that dexamethasone (Dex), a synthetic GC, induced apoptosis in normal
      immature cortical thymocytes which remained unaltered in the presence of Elrich's
      ascitic carcinoma (EAC). PRL protected the normal CD4+ CD8+ cortical thymocytes
      from Dex-induced apoptosis but failed to alter the effect of Dex in tumor-bearing
      mice. Dex-treated normal thymocytes became unresponsive to PRL in presence of
      tumor cell culture supernatant. Low binding affinity of the microsomal membranes
      of thymocytes to PRL and absence of the mRNA of a particular form of prolactin
      receptor (PRL-R) suggest the presence of a different PRL-R in CD4+ CD8+
      thymocytes of EAC-bearing mice. The induction of tumor may alter the PRL-R that
      can be correlated with the failure of PRL in rescuing CD4+ CD8+ immature cortical
      thymocytes from GC induced death.

PMID- 16289332
TI  - Analysis of pediatric burns in Nagasaki University from 1983 to 2002.
AB  - Pediatric burns are frequently observed: twenty-year burn analysis was performed
      in a single department, and 354 cases, aged 0-6 years old. The major cause of
      pediatric burns was scalding (68%) and hot water comprised over half of the scald
      burns. At 1 year old and younger, the total burn surface area (TBSA) was
      significantly smaller than from 1 to 6 years old (4.8+/-9.56 versus 10.5+/
      18.86%, respectively, p<0.001). TBSA of scald burns was significantly greater
      than contact burns (8.9+/-15.76 versus 0.9+/-2.0%, respectively, p<0.05). Surgery
      was performed for 65 patients (18%) and 126 patients were hospitalized (34%).
      Compared to the first decade of analysis, the second decade had fewer patients
      (222 versus 142 cases) and lower severity (7.4+/-14.6% versus 6.6+/-13.26%,
      TBSA). Pediatric burns in younger children should be studied closely as to their
      causes and with further follow-up.

PMID- 16289333
TI  - Minor burn injuries in adults presenting to the regional burns unit in Western
      Australia: a prospective descriptive study.
AB  - INTRODUCTION: Western Australia is the largest state in Australia, accounting for
      approximately one third of the Australian continent. The adult Burns Unit in
      Western Australia is at Royal Perth Hospital, which provides for the whole adult
      population of approximately 1.8 million, 80% of which live in and around the
      state capital city, Perth (approx. 1.4 million). The unit also offers a minor
      burn care facility. METHODS: The aim of this study was to perform the first
      prospective review of minor burn injuries in Western Australia, to classify
      patient demographics, injury patterns and primary treatment. RESULTS AND
      CONCLUSION: Two hundred and twenty seven patients were referred to the minor burn
      facility at Royal Perth Hospital (RPH) during the study period. One hundred and
      three patients (45%) sustained a scald, a further 44 (19%) received a flame burn.
      Thirty-seven (16%) patients sustained a contact burn, 18 (7.8%) patients attended
      the clinic with a chemical burn. Sixty percent of all patients reviewed had burns
      less than one percent. Only 39% of all our patients received adequate first aid.
      Sixty one percent of all patients received inadequate or inappropriate first aid.
      This study highlights a number of important issues. The over representation of
      metropolitan patients coupled with the low numbers of aboriginal patients
      reinforces the need for rural burns education. The best service we can provide is
      education on burns prevention and primary management. There are a number of other
      areas we hope to address in the future, the high incidence of domestic accidents,
      home safety must be a priority, coupled with seasonal promotional campaigns to
      address issues such as car radiator injuries. The most striking, and perhaps the
      most worrying finding in this study is the poor application of basic first aid
      principles. This is something that is unacceptable, needs further investigation
      and the lack of basic knowledge needs to be addressed at all levels of the
      community.

PMID- 16289334
TI  - Attitudes towards vehicle driving behaviour: categorising and contextualising
      risk.
AB  - In driving motorised vehicles, the amount of risk accepted varies between
      individuals. Traditional theories of risk have tended to focus on a lack of skill
      as a function of risk taking and have ignored social motivations and attitudes
      for engaging in risk. This study aims to categorise and contextualise risk taking
      behaviour in relation to car driving through studying the motivations and
      attitudes towards risk. The results were tested on a representative sample
      (n=1655) of the UK driving population and four groups were identified based on
      motivations; those that took risk unintentionally formed the largest group. Three
      smaller groups who took deliberate risks were also found, a reactive risk taking
      group who took risks when reacting to stress or being in a hurry, a calculated
      risk taking group who took risks when they felt it was safe to do so, such as
      late at night or on well-known roads, and a continuous risk taking group who
      frequently took risks for their own sake.

PMID- 16289335
TI  - Does public education improve rail-highway crossing safety?
AB  - Improvements in rail-highway grade crossing safety have resulted from
      engineering, law enforcement, and educating the public about the risks and the
      actions they should take. The primary form of the latter is a campaign called
      Operation Lifesaver which started in the 1970s. This paper uses a negative
      binomial regression to estimate whether variations in Operation Lifesaver
      activity across states and from year-to-year in individual states are related to
      the number of collisions and fatalities at crossings. Annual data on the
      experience in 46 states from 1996 to 2002 are used. The analysis finds that
      increasing the amount of educational activity will reduce the number of
      collisions with a point elasticity of -0.11, but the effect on the number of
      deaths cannot be concluded with statistical certainty.

PMID- 16289336
TI  - Effect of head restraint backset on head-neck kinematics in whiplash.
AB  - Although head restraints were introduced in the 1960s as a countermeasure for
      whiplash, their limited effectiveness has been attributed to incorrect
      positioning. The effect of backset on cervical segmental angulations, which were
      previously correlated with spinal injury, has not been delineated. Therefore, the
      practical restraint position to minimize injury remains unclear. A parametric
      study of increasing head restraint backset between 0 and 140mm was conducted
      using a comprehensively validated computational model. Head retraction values
      increased with increasing backset, reaching a maximum value of 53.5mm for
      backsets greater than 60mm. Segmental angulation magnitudes, greatest at levels
      C5-C6 and C6-C7, reached maximum values during the retraction phase and increased
      with increasing backset. Results were compared to a previously published head
      restraint rating system, wherein lower cervical extension magnitudes from this
      study exceeded mean physiologic limits for restraint positions rated good,
      acceptable, marginal, and poor. As head restraint contact was the limiting factor
      in head retraction and segmental angulations, the present study indicates that
      minimizing whiplash injury may be accomplished by limiting head restraint backset
      to less than 60mm either passively or actively after impact.

PMID- 16289337
TI  - Experience from the development of a diagnostic single tube real-time PCR for
      human caliciviruses, Norovirus genogroups I and II.
AB  - Detection of caliciviruses requires high mutation tolerance and throughput. The
      development of a rational simple, single tube reverse transcription-real-time
      quantitative PCR (QPCR) technique for human noroviruses (NV) is reported here. A
      dual-probe, triple-primer system (NM system) was used for simultaneous detection
      and preliminary differentiation of NV genogroups in fecal samples. The design was
      based on a comprehensive analysis of all 1140 NV sequences available in GenBank.
      A touch-down amplification protocol improved the frequency of detection. The
      final QPCR was evaluated with 71 fecal samples from outbreak and sporadic cases
      in Sweden (1997-2004), all calicivirus-positive by electron microscopy. Up to 56
      (79 %) were positive. The method is more rational than NV detection methods
      described previously, and should be a developmental basis for large-scale routine
      methods for detection of NV.

PMID- 16289338
TI  - First report of aphantoxins in China--waterblooms of toxigenic Aphanizomenon flos
      aquae in Lake Dianchi.
AB  - The oligohaline cyanobacterium Aphanizomenon flos-aquae (L.) Ralfs (A. flos
      aquae) has been reported in several countries to produce paralytic shellfish
      poisons (PSPs) or protracted toxic effects. In the past years, A. flos-aquae
      blooms have occurred annually in the eutrophic Lake Dianchi (300 km(2) in area,
      located in southwestern China). Material from natural blooms dominated by A. flos
      aquae was collected and lyophilized. Acute toxicity testing was performed by
      mouse bioassay using extracts from the lyophilized material. Clear symptoms of
      PSPs intoxications were observed. To confirm the production of PSPs, a strain of
      A. flos-aquae (DC-1) was isolated and maintained in culture. Histopathological
      effects were studied by examining the organ damages using transmission electron
      microscopy (TEM). Slight hepatocytic damage with swollen mitochondria was found.
      The ultrastructural pulmonary lesions were characterized by distortied nuclei and
      indenting of karyotheca, together with degeneration and tumefaction of
      mitochondria and endoplasmic reticulum. Control animals injected with acetic acid
      did not exhibit histopathological damage in any organ. Toxic effects of cultured
      algal cells on enzymatic systems in the mouse were studied using sublethal doses
      of extracts. Significant glutathione-S-transferase (GST) and lactate
      dehydrogenase (LDH) increases, together with decrease of the glutathione (GSH)
      level, were measured. These results indicated a potential role of PSPs
      intoxicating and metabolizing in the test animals. HPLC-FLD and LC/MS analysis of
      extracts from cultured material demonstrated the PSP toxins produced by A. flos
      aquae bloom. To the best of our knowledge, this is the first study reporting
      chemically and toxicologically confirmed PSP toxins related to A. flos-aquae in
      China.

PMID- 16289339
TI  - Adding rituximab to cyclophosphamide, vincristine and prednisone increases time
      to treatment failure or progression in people with untreated stage III/IV
      follicular lymphoma.

PMID- 16289340
TI  - Adjuvant capecitabine is at least as effective as fluorouracil plus leucovorin
      for survival in people with resected stage III colon cancer.

PMID- 16289341
TI  - The chlorinated AHR ligand 3,3',4,4',5-pentachlorobiphenyl (PCB126) promotes
      reactive oxygen species (ROS) production during embryonic development in the
      killifish (Fundulus heteroclitus).
AB  - Exposure to dioxin-like chemicals that activate the aryl hydrocarbon receptor
      (AHR) can result in increased cellular and tissue production of reactive oxygen
      species (ROS). Little is known of these effects during early fish development. We
      used the fish model, Fundulus heteroclitus, to determine if the AHR ligand and
      pro-oxidant 3,3',4,4',5-pentachlorobiphenyl (PCB126) can increase ROS production
      during killifish development, and to test a novel method for measuring ROS non
      invasively in a living organism. The superoxide-sensitive fluorescent dye,
      dihydroethidium (DHE), was used to detect in ovo ROS production microscopically
      in developing killifish exposed to PCB126 or vehicle. Both in ovo CYP1A activity
      (ethoxyresorufin-o-deethylase, EROD) and in ovo ROS were induced by PCB126. In
      ovo CYP1A activity was inducible by PCB126 concentrations as low as 0.003 nM,
      with maximal induction occurring at 0.3 nM PCB126. These PCB126 concentrations
      also significantly increased in ovo ROS production in embryonic liver, ROS being
      detectable as early as 5 days post-fertilization. These data demonstrate that the
      pro-oxidant and CYP1A inducer, PCB126, increases both CYP1A activity and ROS
      production in developing killifish embryos. The superoxide detection assay (SoDA)
      described in this paper provides a semi-quantitative, easily measured, early
      indicator of altered ROS production that can be used in conjunction with
      simultaneous in ovo measurements of CYP1A activity and embryo development to
      explore functional relationships among biochemical, physiological and
      developmental responses to AHR ligands.

PMID- 16289342
TI  - Metallothioneins in aquatic invertebrates: their role in metal detoxification and
      their use as biomarkers.
AB  - The literature on metallothioneins (MT) and metallothionein-like proteins (MTLP)
      in aquatic invertebrates is large and increasing, and yet inconsistencies and
      confusion remain, not least over the physiological role of MT and their use as
      biomarkers in environmental monitoring programmes. We have collated published
      information on MT in three important groups of aquatic invertebrates-the
      molluscs, crustaceans and annelid worms, and attempted to seek explanations for
      some of the apparent inconsistencies present in the dataset. MTs can be induced
      by the essential metals Cu and Zn and the non-essential metals Cd, Ag and Hg in
      both vertebrates and invertebrates, but their induction is variable. Such
      variation is intraspecific and interspecific, and is down to a variety of reasons
      environmental and physiological explored here. Against this background of
      variability MTs do appear to play roles both in the routine metabolic handling of
      essential Cu and Zn, but also in the detoxification of excess amounts
      intracellularly of these metals and of non-essential Cd, Ag and Hg. Different
      isoforms of MT probably play different physiological roles, and the dependence on
      MT in detoxification processes varies environmentally and between zoological
      groups. MTs can be used as biomarkers if used wisely in well-designed
      environmental monitoring programmes.

PMID- 16289343
TI  - Evaluation of gene expression endpoints in the context of a Xenopus laevis
      metamorphosis-based bioassay to detect thyroid hormone disruptors.
AB  - Thyroid hormones (TH) are important in growth, development and the maintenance of
      proper cellular metabolism in vertebrates. Amphibian metamorphosis is completely
      dependent on TH and forms the basis of a screen for thyroid axis disrupting
      chemicals that currently relies on external morphological endpoints and changes
      in thyroid gland histology. The requirement for TH-dependent gene expression
      makes it possible to augment this screen through the addition of molecular
      endpoints. In order to do this, gene selection, choice of sampling time, tissue
      sensitivity, and their relationship to morphological change must all be
      considered. We exposed stage 54 Xenopus laevis tadpoles to a concentration series
      of the THs, thyroxine (T4) and 3,5,3'-triiodothyronine (T3), and three known TH
      antagonists, methimazole, propylthiouracil (PTU), and perchlorate. The agonists
      significantly accelerated metamorphosis as defined by developmental stage
      attained after 14 days. In contrast, the TH antagonists significantly delayed
      metamorphosis at 14 days and caused an increase in thyroid gland size at day 8.
      We assessed the changes in steady-state mRNA levels of thyroid hormone receptor
      alpha- and beta-isoforms and the basic transcription element binding (BTEB)
      protein by quantitative real-time polymerase chain reaction. Three tissues
      (brain, tail and hindlimb) were analyzed at 24, 48 and 96 h and we found that TH
      receptor, TRbeta, and BTEB were the most sensitive gene transcripts for the TH
      agonists, whereas only TRalpha displayed significant changes upon antagonist
      exposure. We detected differences in tissue-specific responses between the two
      agonists. We matched the concentrations of T3 and T4 that elicited similar
      biological responses at 14 days and compared the induction of gene expression. At
      96 h, the TRbeta and BTEB expression response to T3 and T4 was similar in the
      tail. In contrast, T3 elicited no concentration-dependent changes in TRbeta and
      BTEB expression in the brain, whereas T4 elevated their expression. The tail
      showed the highest correlation between TH concentration and morphological outcome
      whereas the brain was the most sensitive to antagonist treatment. Only
      methimazole and perchlorate showed significant changes in TRalpha gene expression
      in the brain whereas PTU did not suggesting differences in cellular mechanisms of
      action. The greatest effect on gene expression occurred within 48 h with many of
      the hormone-dependent changes disappearing by 96 h. This study accentuates the
      need to examine multiple tissues and provides critical information required for
      optimization of exposure regimens and endpoint assessments that focus on the
      detection of disruption in TH-regulatory systems.

PMID- 16289344
TI  - Comparison between two clones of Daphnia magna: effects of multigenerational
      cadmium exposure on toxicity, individual fitness, and biokinetics.
AB  - We investigated the effects of genotype (two different clones) and
      multigenerational Cd-exposure history on Cd toxicity, individual fitness, and
      biokinetics in populations of a freshwater cladoceran Daphnia magna. The adults
      of the tolerant (T) clone had longer mean-survival-time than the sensitive (S)
      clone in both control groups (without Cd-exposure) and continuous Cd-exposure
      groups, but the two clones showed comparable resistances to acute Cd stress in
      the recovery groups. The body concentration of metallothionein (MT) played a
      critical role in handling Cd stress, which mainly accounted for the significant
      difference between the two clones in terms of survival distribution. High
      comparability of these two clones in individual fitness parameters and
      biokinetics suggested that these parameters are unlikely driven by genetic
      variation. For each specific clone, continuous Cd-exposure inhibited the animal
      growth, elevated the MT induction, and increased the Cd uptake rate (ingestion
      rate, assimilation efficiency from dietary phase, and uptake rate from dissolved
      phase), all of which enhanced the weight-specific Cd accumulation in daphnids'
      bodies. The strong dependence of biokinetic parameters on environmental factors
      (e.g., food concentrations, pH, dissolved or dietary metal concentration, and
      metal exposure histories) rather than on genotypes implied the great potential of
      using biokinetics in inter-lab comparisons and environmental risk assessments.

PMID- 16289346
TI  - Development of a spectrophotometric assay for cyclase activity.
AB  - We describe the development of a rapid colorimetric assay for soluble guanylate
      cyclase (sGC) activity adapted for a 96-well microplate. The assay greatly
      decreases the analysis time and cost over traditional methodologies based on
      radio- and immunoassays and high-performance liquid chromatography (HPLC)
      separations. The method does not demonstrate any significant interference with
      chemicals commonly used for sGC purification and reaction kinetics. The assay
      converts the inorganic pyrophosphate produced in the cyclase reaction to
      inorganic phosphate, which is then measured using a modified Fiske-Subbarow
      assay. We used the assay to compare the reaction kinetics of preparations of sGC
      from a commercial source with those from our lab with Mg(2+)-guanosine 5'
      triphosphate (GTP) or Mn(2+)-GTP as a substrate. The commercial preparation was
      found to have a specific activity of around 1.5 micromol/min/mg, which is
      significantly lower than expected, as was the fold-activation upon addition of
      nitric oxide (NO). Our laboratory preparation had a higher specific activity that
      was consistent with results from HPLC assays. We determined that the human
      isoform of sGC is more active in the basal and NO forms with Mn(2)-GTP as a
      substrate than Mg(2+)-GTP, a feature more similar to rat lung sGC than the more
      commonly studied bovine lung.

PMID- 16289345
TI  - Development of the loop-mediated isothermal amplification method for rapid
      detection of cytomegalovirus DNA.
AB  - Cytomegalovirus (CMV) loop-mediated isothermal amplification (LAMP) was performed
      on DNA extracted from CMV (AD-169)-, herpes simplex virus (HSV) 1 (KOS)-, HSV-2
      (186)-, varicella-zoster virus (Oka-vaccine)-, human herpesvirus (HHV)-6 A
      (U1102)-, HHV-6 B (Z29)-, and HHV-7 (RK)-infected cells. Although amplified CMV
      demonstrated typical ladder patterns, no LAMP product was detected in reactions
      performed with other viral DNAs. The sensitivity of the CMV LAMP was 500
      copies/tube, as determined by either agarose gel electrophoresis or turbidity
      assay. To determine whether CMV LAMP could be used for quantitative analysis of
      viral DNA, threshold times, defined as the time (in seconds) to reach the
      threshold level (0.1), were measured by amplification of serial dilutions of the
      plasmid DNA. The standard curve exhibited a correlation coefficient of 0.944, a
      slope of -208.1, and a y-intercept of 3261.4. Following these initial validation
      experiments, we analyzed 180 samples collected serially from 20 pediatric
      hematopoietic stem cell transplant recipients. Detection of CMV DNA in whole
      blood (WB) was tested by CMV LAMP and real-time polymerase chain reaction (PCR).
      When >500 copies/tube (>5000 copies/200 microl of WB) was defined as positive for
      CMV infection, the sensitivity, specificity, positive predictive value, and
      negative predictive values of the CMV LAMP were 80.0, 98.9, 66.7, and 99.4%,
      respectively.

PMID- 16289347
TI  - Capillary affinity electrophoresis using lectins for the analysis of milk
      oligosaccharide structure and its application to bovine colostrum
      oligosaccharides.
AB  - Animal colostrum and milk contain complex mixtures of oligosaccharides, which
      have species-specific profiles. Milk oligosaccharides have various types of
      structure related to the core structures of glycolipids and N- and O-glycans of
      glycoproteins and provide a good library to examine the binding of
      oligosaccharides to various lectins. Recently, we reported a capillary affinity
      electrophoresis (CAE) method for analyzing the interactions between lectins and
      complex mixtures of N-linked oligosaccharides prepared from serum glycoproteins.
      The present paper reports the interactions between 24 milk oligosaccharides and
      six lectins (PA-I, RCA(120), SBA, WGA, UEA-I, and AAL) analyzed using CAE. Based
      on the resulting data, we constructed a library that enables us to determine
      nonreducing terminal monosaccharides, such as Gal, GalNAc, GlcNAc, and Fuc, and
      to differentiate Gal- or Fuc-linked isomers, such as lacto-N-tetraose, lacto-N
      neotetraose, and lacto-N-fucopentaose II and III. In addition, using the library,
      we show that a combination of the lectins can characterize the neutral
      oligosaccharides derived from bovine colostrum.

PMID- 16289349
TI  - Post-training N-methyl-D-aspartate receptor blockade offers protection from
      retrograde interference but does not affect consolidation of weak or strong
      memory traces in the water maze.
AB  - Memory consolidation is the process where labile memory traces become long
      lasting, stable memories. Previous work has demonstrated that spatial memory
      consolidation, several days after training in a water maze had ceased, can be
      disrupted by a temporary intra hippocampal infusion of the alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid/kainate antagonist LY326325 (Riedel et al.,
      1999). Such reversible pharmacological techniques offer advantages over the
      permanent lesion studies that had first suggested a role for the hippocampus in
      memory consolidation. However, to date the role of N-methyl-D-aspartate receptors
      in such systems level processes remains controversial with evidence for
      impairments and augmentation of performance. Here we investigate the role of post
      training hippocampal N-methyl-D-aspartate receptor blockade in rats and mice on
      the consolidation of weak and strong memory traces using an Atlantis water maze
      protocol. A hidden Atlantis platform was employed and rats (experiments 1 and 2)
      and mice (experiment 3) were required to dwell within 20 cm of the trained
      location to activate and subsequently reveal the escape platform. In experiments
      1 and 3 a strong memory trace was established by training rats or mice for
      several days in the water maze. In experiment 2 a significantly weaker trace was
      instituted by reducing the training period. N-methyl-D-aspartate receptor
      blockade was induced after the last training trial and continued for seven days.
      Reliable memory for the trained platform location in a retention test 15 days
      after the last training day demonstrated that N-methyl-D-aspartate receptor
      blockade did not affect memory consolidation in rats or mice. Our results also
      show that post-training N-methyl-D-aspartate receptor blockade can lead to better
      performance in further retention tests conducted after the consolidation and drug
      administration period. Those data suggest that specific post-training N-methyl-D
      aspartate receptor blockade does not impair memory consolidation and it may also
      offer a memory trace mild protection from retrograde interference.

PMID- 16289348
TI  - Subcellular localization of type 1 cannabinoid receptors in the rat basal
      ganglia.
AB  - Endocannabinoids, acting via type 1 cannabinoid receptors (CB1), are known to be
      involved in short-term synaptic plasticity via retrograde signaling. Strong
      depolarization of the postsynaptic neurons is followed by the endocannabinoid
      mediated activation of presynaptic CB1 receptors, which suppresses GABA and/or
      glutamate release. This phenomenon is termed depolarization-induced suppression
      of inhibition (DSI) or excitation (DSE), respectively. Although both phenomena
      have been reported to be present in the basal ganglia, the anatomical substrate
      for these actions has not been clearly identified. Here we investigate the high
      resolution subcellular localization of CB1 receptors in the nucleus accumbens,
      striatum, globus pallidus and substantia nigra, as well as in the internal
      capsule, where the striato-nigral and pallido-nigral pathways are located. In all
      examined nuclei of the basal ganglia, we found that CB1 receptors were located on
      the membrane of axon terminals and preterminal axons. Electron microscopic
      examination revealed that the majority of these axon terminals were GABAergic,
      giving rise to mostly symmetrical synapses. Interestingly, preterminal axons
      showed far more intense staining for CB1, especially in the globus pallidus and
      substantia nigra, whereas their terminals were only faintly stained. Non
      varicose, thin unmyelinated fibers in the internal capsule also showed strong CB1
      labeling, and were embedded in bundles of myelinated CB1-negative axons. The
      majority of CB1 receptors labeled by immunogold particles were located in the
      axonal plasma membrane (92.3%), apparently capable of signaling cannabinoid
      actions. CB1 receptors in this location cannot directly modulate transmitter
      release, because the release sites are several hundred micrometers away.
      Interestingly, both the CB1 agonist, WIN55,212-2, as well as its antagonist,
      AM251, were able to block action potential generation, but via a CB1 independent
      mechanism, since the effects remained intact in CB1 knockout animals. Thus, our
      electrophysiological data suggest that these receptors are unable to influence
      action potential propagation, thus they may not be functional at these sites, but
      are likely being transported to the terminal fields. The present data are
      consistent with a role of endocannabinoids in the control of GABA, but not
      glutamate, release in the basal ganglia via presynaptic CB1 receptors, but also
      call the attention to possible non-CB1-mediated effects of widely used
      cannabinoid ligands on action potential generation.

PMID- 16289350
TI  - Differential expression of ryanodine receptors in the rat cochlea.
AB  - This study examined the localization and functional expression of ryanodine
      receptors (RyR) within the cochlea using a combination of reverse transcription
      polymerase chain reaction, immunolabeling techniques, and confocal Ca2+ imaging.
      All three RyR isoform mRNA transcripts were detected in the adult rat cochlea.
      Immunoperoxidase and immunofluorescence labeling showed that the three isoforms
      were differentially expressed. The most pronounced RyR protein expression,
      involving all three isoforms, occurred in the cell bodies of the spiral ganglion
      neurons. RyR3 labeling extended to the synaptic terminals innervating the inner
      and outer hair cells. RyR2 expression also occurred in the inner hair cells and
      supporting cells of the organ of Corti, while cells associated with ion
      homeostasis in the cochlea, such as the interdental cells of the spiral limbus
      (RyR1), and the epithelial cells of the spiral prominence and basal cells of the
      stria vascularis (RyR2 and RyR3), were also immunopositive. The functionality of
      RyR-gated Ca2+ stores in the spiral ganglion neurons was shown by confocal
      calcium imaging of fluo-4 fluorescence in rat cochlear slices. Caffeine (5 mM)
      evoked an increase in intracellular Ca2+ concentration in the cell bodies of the
      spiral ganglion neurons which occurred inthe absence of external Ca2+. Ryanodine
      (50 nm-1 microM) evoked comparable increases in intracellular Ca2+ concentration.
      These findings suggest that RyR-mediated Ca2+ release may be involved in auditory
      neurotransmission, sound transduction, and cochlear electrochemical homeostasis.

PMID- 16289351
TI  - Serotonin1A autoreceptor activation by S 15535 enhances circadian activity
      rhythms in hamsters: evaluation of potential interactions with serotonin2A and
      serotonin2C receptors.
AB  - Mammalian circadian activity rhythms are generated by pacemaker cells in the
      suprachiasmatic nucleus (SCN). As revealed by the actions of diverse agonists,
      serotonergic input from raphe nuclei generally inhibits photic signaling in the
      suprachiasmatic nucleus. In contrast, the serotonin (5HT)1A partial agonist, 4
      (benzodioxan-5-yl)1-(indan2-yl)piperazine (S 15535), was found to enhance the
      phase-shifting influence of light on hamster circadian rhythms [Gannon,
      Neuroscience 119 (2003) 567]. Herein, we extend this observation in showing that
      S 15535 (5.0 mg/kg, i.p.) markedly (275%) enhanced the light-induced phase shift
      in circadian activity rhythms: further, this action was dose-dependently
      abolished by the highly-selective 5HT1A receptor antagonist, WAY 100,635 (N-[2-[4
      (2-methoxyphenyl)-1-piperazinyl]ethyl]N-2-pyridinyl-cyclohexane-carboxamide
      maleate) (0.1-0.5 mg/kg, i.p.). WAY 100,635, which was inactive alone, shares the
      antagonist actions of S 15535 at postsynaptic 5HT1A sites, yet blocks its effects
      at their presynaptic counterparts. Thus, 5HT1A autoreceptor activation must be
      involved in this effect of S 15535 which contrasts with the opposite, inhibitory
      influence upon phase shifts of the "full" agonist, 8-OH-DPAT, which acts by
      stimulation of postsynaptic 5HT1A receptors [Rea et al., J Neurosci 14 (1994)
      3635]. Despite the occurrence of 5HT2A and 5HT2C receptors in the (rat)
      suprachiasmatic nucleus, their influence on circadian rhythms is unknown since
      actions of selective ligands have never been evaluated. This issue was
      investigated with the most selective agents currently available. However, the
      5HT2A agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.25 and 0.5
      mg/kg), and the 5HT2C agonist, alphaS-6-chloro-5-fluoro-a-methyl-1H-indole-1
      ethanamine fumarate (Ro-60-0175) (1.0 and 5.0 mg/kg), failed to affect light
      induced phase shifts in hamsters. Moreover, even over broad dose-ranges, the
      5HT2A antagonist, (+)-(2,3-dimethoxy-phenyl)-[1-[2-(4-fluoro-phenyl)-ethyl]
      piperidin-4-yl]methanol (MDL 100,907) (0.1-1.0 mg/kg), and the 5HT2C antagonist,
      6-chloro-5-methyl-1-[6-(2-methylpyridin-3-yloxy)pyridin-3-yl carbamoyl]indoline
      (SB 242,084) (1.0-10.0 mg/kg), were likewise inactive. In view of evidence that
      5HT2A and 5HT2C sites functionally interact with 5HT1A receptors, we also
      examined the influence of these agents upon the actions of S 15535, but no
      significant alteration was seen in its enhancement of rhythms. In conclusion, S
      15535 elicits a striking enhancement of light-induced phase shifts in circadian
      rhythms by specifically recruiting 5HT1A autoreceptors, which leads to
      suppression of serotonergic input to the suprachiasmatic nucleus. Surprisingly,
      no evidence for a role of 5HT2A or 5HT2C sites was found, though comparable
      functional studies remain to be undertaken in rats. Indeed, the present work
      underlines the importance of comparative studies of circadian rhythms in various
      species, as well as the need for further study of potential interactions among
      5HT receptor subtypes in their control.

PMID- 16289352
TI  - Chronic and acute effects of 3,4-methylenedioxy-N-methylamphetamine ('Ecstasy')
      administration on the dynorphinergic system in the rat brain.
AB  - The prodynorphin system is implicated in the neurochemical mechanism of
      psychostimulants. Exposure to different drugs of abuse can induce
      neuroadaptations in the brain and affect opioid gene expression. The present
      study aims to examine the possibility of a common neurobiological substrate in
      drug addiction processes. We studied the effects of single and repeated 3,4
      methylenedioxy-N-methylamphetamine ('Ecstasy') on the gene expression of the
      opioid precursor prodynorphin, and on the levels of peptide dynorphin A in the
      rat brain. Acute (8 mg/kg, intraperitoneally) 3,4-methylenedioxy-N
      methylamphetamine markedly raised, two hours later, prodynorphin mRNA levels in
      the prefrontal cortex, and in the caudate putamen, whereas it decreased gene
      expression in the ventral tegmental area. Chronic (8 mg/kg, intraperitoneally,
      twice a day for 7 days) 3,4-methylenedioxy-N-methylamphetamine increased
      prodynorphin mRNA in the nucleus accumbens, hypothalamus and caudate putamen and
      decreased it in the ventral tegmental area. Dynorphin A levels increased after
      chronic treatment in the ventral tegmental area and decreased after acute
      treatment in the nucleus accumbens, prefrontal cortex and hypothalamus. These
      findings confirm the role of the dynorphinergic system in mediating the effects
      of drugs of abuse, such as 3,4-methylenedioxy-N-methylamphetamine, in various
      regions of the rat brain, which may be important sites for the opioidergic
      mechanisms activated by addictive drugs.

PMID- 16289353
TI  - Neuroprotective effects of tacrolimus (FK506) in a model of ischemic cortical
      cell cultures: role of glutamate uptake and FK506 binding protein 12 kDa.
AB  - BACKGROUND: The mechanisms underlying the neuroprotective effects of the
      immunosuppressant tacrolimus, observed in vivo, remain unclear. Here we quantify
      these effects in vitro, and evaluate the potential involvement of the glutamate
      and/or immunophilin FK506 binding protein 12 kDa in tacrolimus-induced
      neuroprotection. METHODS: Primary cultures of neurons and astrocytes from rat
      cerebral cortex were subjected to transient oxygen-glucose deprivation. Neuronal
      injury was evaluated by cell counting after immunostaining experiments, lactate
      dehydrogenase release and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium
      bromide reduction. The involvement of the immunophilin FK506 binding protein 12
      kDa was explored using an anti-FK506 binding protein 12 kDa antibody, (3-3
      pyridyl)-1-propyl(2 s)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidine carboxylate
      and rapamycin. Extracellular glutamate and glutamate uptake were respectively
      measured by high performance liquid chromatography and l-[3H]glutamate
      incorporation. RESULTS: When added during either oxygen-glucose deprivation or
      reoxygenation, FK506 (50-500 pM) offered significant neuroprotection. During
      oxygen-glucose deprivation, it was able to reverse the oxygen-glucose deprivation
      induced increase in extracellular glutamate and decrease in glutamate uptake and
      this effect was reversed in the presence of threo-3-methyl glutamate, a specific
      inhibitor of glutamate transporter-1. Blocking FK506 binding protein 12 kDa
      inhibited the neuroprotection induced by tacrolimus added during either oxygen
      glucose deprivation or reoxygenation. Tacrolimus-induced neuroprotection was also
      reversed in the presence of rapamycin, an immunosuppressant FK506 binding protein
      12 kDa ligand devoid of neuroprotective properties and (3-3-pyridyl)-1-propyl(2
      s)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidine carboxylate, a non
      immunosuppressant ligand of FK506 binding protein 12 kDa, exerteing
      neuroprotective effects. CONCLUSION: The beneficial effects of tacrolimus during
      in vitro ischemia/reperfusion seem to indicate the restoration of a glutamate
      transporter-1-mediated activity and could be mediated by a FK506 binding protein
      12 kDa pathway.

PMID- 16289354
TI  - Raised circulating corticosterone inhibits neuronal differentiation of progenitor
      cells in the adult hippocampus.
AB  - Neurons are added throughout life to the dentate gyrus of the hippocampus of the
      mammalian brain. Progenitors residing in the dentate gyrus progress through three
      distinct stages of adult neurogenesis: proliferation, survival and
      differentiation. One of the most potent factors which regulates adult
      neurogenesis is adrenal-derived glucocorticoids. Raised levels of glucocorticoids
      suppress progenitor division, while removal of glucocorticoids by adrenalectomy
      stimulates proliferation of these cells in the dentate gyrus. We have recently
      reported that both pre- and post-mitotic corticoid environments powerfully
      regulate survival of progenitor cells in a time-dependent manner. However, it is
      unknown if glucocorticoids alter the process of neuronal differentiation, since
      not all of the newly-formed cells acquire a neuronal fate during development.
      Here we employ triple immuno-fluorescence staining techniques to phenotype
      surviving progenitor cells 28 days after labeling. Results show that high levels
      of corticosterone (the major glucocorticoid in rodents) either before or after
      progenitor labeling discouraged the acquisition of neuronal fate. Similar to its
      effect on survival, post-mitotic corticosterone also regulates neuronal
      differentiation in a time-dependent fashion, but this action is most prominent
      from around 19-27 days after the cells were born. In contrast, a corticoid-free
      environment either before or after progenitor proliferation did not affect
      neuronal differentiation. Combining these data with previous survival data
      obtained from the same animals allowed us to estimate the total number of neurons
      formed resulting from different corticoid treatments. Raised corticosterone
      significantly reduced neuronal production while adrenalectomy resulted in
      significantly higher number of neurons in the adult male rat hippocampus.

PMID- 16289355
TI  - Combinatorial RNAi on intestinal cathepsin B-like proteinases in Caenorhabditis
      elegans questions the perception of their role in nematode biology.

PMID- 16289356
TI  - Trypanosoma brucei DMC1 does not act in DNA recombination, repair or antigenic
      variation in bloodstream stage cells.
AB  - Homologous recombination acts in the repair of cellular DNA damage and can
      generate genetic variation. Some of this variation provides a discrete purpose in
      the cell, although it can also be genome-wide and contribute to longer-term
      natural selection. In Trypanosoma brucei, a eukaryotic parasite responsible for
      sleeping sickness disease in sub-Saharan Africa, homologous recombination acts to
      catalyse antigenic variation, an immune evasion strategy involving switches in
      variant surface glycoprotein. In addition, T. brucei can undergo genetic exchange
      by homologous recombination in the tsetse vector, and some evidence suggests that
      this occurs by meiosis. Here, we show that T. brucei, Trypanosoma cruzi and
      Leishmania major each contain a single copy gene whose product is highly related
      to the eukaryotic meiosis-specific protein Dmc1, which is structurally and
      functionally related to Rad51. We show that T. brucei DMC1 is transcribed in the
      bloodstream stage of the parasite, where the gene can be mutated by reverse
      genetic disruption. DMC1 mutation does not, however, result in detectable
      alterations in DNA repair, recombination or antigenic variation efficiency in
      this life cycle stage.

PMID- 16289357
TI  - Upregulation of expression of the reticulocyte homology gene 4 in the Plasmodium
      falciparum clone Dd2 is associated with a switch in the erythrocyte invasion
      pathway.
AB  - The Plasmodium falciparum clone, Dd2, that requires sialic acid for invasion can
      switch to a sialic acid independent pathway, Dd2(NM). To elucidate the molecular
      basis of the switch in invasion phenotype of Dd2 to Dd2(NM), we performed
      expression profiling of the parasites using an oligonucleotide microarray and
      real-time RT-PCR. We found that four genes were upregulated in Dd2(NM) by
      microarray analysis, only two of which could be confirmed by real time RT-PCR.
      One gene, PfRH4, is a member of the reticulocyte homology family and the other,
      PEBL, is a pseudogene of the Duffy binding-like family. The two genes are
      contiguous but transcribed in opposite directions. The DNA sequence of these
      ORFs, their 5'-intergenic region and a 1.1kb region 3' to each ORF are identical
      between Dd2 and Dd2(NM), suggesting that their transcription upregulation relates
      to transactivating factors. The transcription upregulation of PfRH4 was reflected
      at the protein level as PfRH4 protein expression was detected in Dd2(NM) and not
      in Dd2. Other sialic acid independent and dependent clones of P. falciparum
      showed variable transcript levels of PfRH4 and PEBL, unrelated to their
      dependence on sialic acid for invasion, suggesting that different P. falciparum
      clones use different receptors for sialic acid independent invasion. As Dd2(NM)
      is a selected subclone of Dd2, the marked upregulation of PfRH4 expression in
      Dd2(NM) suggests its role in erythrocyte invasion through the sialic acid
      independent pathway of Dd2(NM).

PMID- 16289358
TI  - Biochemical and functional characterization of phosphoserine aminotransferase
      from Entamoeba histolytica, which possesses both phosphorylated and non
      phosphorylated serine metabolic pathways.
AB  - The enteric protozoan parasite Entamoeba histolytica is a unicellular eukaryote
      that possesses both phosphorylated and non-phosphorylated serine metabolic
      pathways. In the present study, we described enzymological and functional
      characterization of phosphoserine aminotransferase (PSAT) from E. histolytica. E.
      histolytica PSAT (EhPSAT) showed maximum activity for the forward reaction at
      basic pH, dissimilar to mammalian PSAT, which showed sharp neutral optimum pH.
      EhPSAT activity was significantly inhibited by substrate analogs, O-phospho-d
      serine, O-phospho-l-threonine, and O-acetylserine, suggesting possible regulation
      of the amoebic PSAT by these metabolic intermediates. Fractionation of the whole
      parasite lysate and rEhPSAT by anion exchange chromatography verified that EhPSAT
      represents a dominant PSAT activity. EhPSAT showed a close kinship to PSAT from
      bacteroides based on amino acid alignment and phylogenetic analyses, suggesting
      that E. histolytica gained this gene from bacteroides by lateral gene transfer.
      Comparisons of kinetic properties of recombinant PSAT from E. histolytica and
      Arabidopsis thaliana showed that EhPSAT possesses significantly higher affinity
      toward glutamate than the A. thaliana counterpart, which may be explained by
      significant differences in the isoelectric point and the substitution of
      arginine, which is involved the binding to the gamma-carboxylate moiety of
      glutamate, in Escherichia coli PSAT, to serine or threonine in E. histolytica or
      A. thaliana PSAT, respectively. Heterologous expression of EhPSAT successfully
      rescued growth defect of a serine-auxotrophic E. coli strain KL282, where serC
      was deleted, confirming its in vivo role in serine biosynthesis. Together with
      our previous demonstration of phosphoglycerate dehydrogenase, the present study
      reinforces physiological significance of the phosphorylated pathway in amoeba.

PMID- 16289359
TI  - Ergonomics of abrasive blasting: a comparison of high pressure water and steel
      shot.
AB  - Abrasive blasting with silica sand has long been associated with silicosis.
      Alternatives to sand are being used increasingly. While NIOSH has done extensive
      investigations of the respiratory effects of the substitutes for sand, the
      ergonomic effects of the substitutes have not been examined. Too often, hazards
      are shifted, and technologies that might save workers' lungs could do so at the
      expense of their musculoskeletal systems. Hence, the objective of this study was
      to examine the ergonomic effects of alternatives to sand. Multiple methods, both
      qualitative and quantitative, were used to yield numerous kinds of data for the
      analysis of exposures to abrasive blasters. PATH, a method for quantifying
      ergonomic exposure in non-routine work, was combined with interviews with
      workers, biomechanical modeling and noise level readings to assess the ergonomics
      of two abrasive blasting operations: high-pressure water and steel shot.
      Advantages and disadvantages of each medium are discussed. High-pressure water
      was slightly less ergonomically stressful, environmentally cleaner, much quieter
      and less dusty that steel shot, and it was reported to be slower on those tasks
      where both media could be used.

PMID- 16289360
TI  - Maternal serum concentrations of BDNF and depression in the perinatal period.
AB  - There is accumulating evidence that a deficiency in brain-derived neurotrophic
      factor (BDNF) plays a critical role in the pathophysiology of depression. This is
      in line with the postulate that low BDNF levels in serum are associated with
      depression. However, the regulation of maternal BDNF serum levels in the
      perinatal period, and its relationship to maternal depression is unknown. In this
      study, serum BDNF concentrations were measured in 40 pregnant (follow-up: 30th
      and 37th week of gestation, 1 week and 8 weeks after childbirth) and 40 non
      pregnant women (20-40 years old). The Edinburgh Postnatal Depression Scale (EPDS)
      was assessed in all subjects at all time points. Maternal serum levels of BDNF
      were markedly decreased, both before and after childbirth (median: <30% of non
      pregnant controls). BDNF correlated with decreased Serotonin (5-HT) levels in
      serum (r>0.6 and p<0.001 at all time points). In contrast, there was no
      association with altered estrogen, progesterone, dehydroepiandrosterone or
      cortisol concentrations in serum. There were significantly higher cortisol levels
      in cases of maternal depression (EPDS scores>9 points) than in cases without
      depression. There was a trend to a decrease of BDNF and 5-HT levels in cases of
      maternal depression (as compared to cases without depression), but this was not
      significant. In conclusion, we demonstrate that women display markedly decreased
      BDNF serum levels before and after childbirth. This phenomenon might reflect an
      increased risk for the development of mood disorders in the perinatal period.
      However, the individual serum concentration of BDNF alone did not predict
      maternal depression in our study.

PMID- 16289361
TI  - Raised plasma nerve growth factor levels associated with early-stage romantic
      love.
AB  - Our current knowledge of the neurobiology of romantic love remains scanty. In
      view of the complexity of a sentiment like love, it would not be surprising that
      a diversity of biochemical mechanisms could be involved in the mood changes of
      the initial stage of a romance. In the present study, we have examined whether
      the early romantic phase of a loving relationship could be associated with
      alterations in circulating levels of neurotrophins (NTs). Plasma levels of NGF,
      BDNF, NT-3 and NT-4 were measured in a total of 58 subjects who had recently
      fallen in love and compared with those of two control groups, consisting of
      subjects who were either single or were already engaged in a long-lasting
      relationship. NGF level was significantly higher (p < 0.001) in the subjects in
      love [mean (SEM): 227 (14) pg/ml] than in either the subjects with a long-lasting
      relationship [123 (10) pg/ml] or the subjects with no relationship [149 (12)
      pg/ml]. Notably, there was also a significant positive correlation between levels
      of NGF and the intensity of romantic love as assessed with the passionate love
      scale (r = 0.34; p = 0.007). No differences in the concentrations of other NTs
      were detected. In 39 subjects in love who-after 12-24 months-maintained the same
      relationship but were no longer in the same mental state to which they had
      referred during the initial evaluation, plasma NGF levels decreased and became
      indistinguishable from those of the control groups. Taken together, these
      findings suggest that some behavioural and/or psychological features associated
      with falling in love could be related to raised NGF levels in the bloodstream.

PMID- 16289362
TI  - Mutation in the flexible loop of 1-deoxy-D-xylulose 5-phosphate reductoisomerase
      broadens substrate utilization.
AB  - The second enzyme in the methylerythritol phosphate pathway to isoprenoids, 1
      deoxy-D-xylulose 5-phosphate reductoisomerase (DXR; EC 1.1.1.267) mediates the
      transformation of 1-deoxy-D-xylulose 5-phosphate (DXP) into 2-C-methyl-D
      erythritol 4-phosphate. Several DXR mutants have been prepared to study amino
      acid residues important in binding or catalysis, but in-depth studies of many
      conserved residues in the flexible loop portion of the enzyme have not been
      conducted. In the course of our studies of this enzyme, an analog of DXP, 1,2
      dideoxy-D-threo-3-hexulose 6-phosphate (1-methyl-DXP), was found to be a weak
      competitive inhibitor. Using the X-ray crystal structures of DXR as a guide, a
      highly conserved tryptophan residue in the flexible loop was identified that
      potentially blocks the use of this analog as a substrate. To test this
      hypothesis, four mutants of the Synechocystis sp. PCC6803 DXR were prepared and a
      W204F mutant was found to utilize the analog as a substrate.

PMID- 16289363
TI  - Probing the CYP3A4 active site by cysteine scanning mutagenesis and photoaffinity
      labeling.
AB  - The mechanism of CYP3A4-substrate interactions has been investigated using a
      battery of techniques including cysteine scanning mutagenesis, photoaffinity
      labeling, and structural modeling. In this study, cysteine scanning mutagenesis
      was performed at seven sites within CYP3A4 proposed to be involved in substrate
      interaction and/or cooperativity. Photolabeled CYP3A4 peptide adducts were
      further characterized by mass spectrometric analysis for each mutant after
      proteolytic digestion and isolation of fluorescent photolabeled peptides. Among
      the tryptic peptides of seven tested mutants, three photolabeled peptides of the
      F108C mutant, ECYSVFTNR (positions 97-105), VLQNFSFKPCK (positions 459-469), and
      RPCGPVGFMK (positions 106-115) were identified by MALDI-TOF-MS and nano-LC/ESI
      QTOF MS. The site of modification was further localized to the substituted Cys
      108 residue in the mutant peptide adduct RPCGPVGFMK (positions 106-115) by nano
      LC/ESI QTOF MS/MS. In summary, we described a potentially useful method to study
      P450 active sites using a combination of cysteine scanning mutagenesis and
      photoaffinity labeling.

PMID- 16289364
TI  - Cloning and analysis of the murine Foxi2 transcription factor.
AB  - Forkhead transcription factors comprise a large family of key regulators of
      embryonic development. Here, we describe the cloning and analysis of the murine
      Foxi2 gene, coding for a putative 311 amino acid protein resembling Foxi
      subfamily members in mice and other species. Expression analysis during the final
      stages of embryonic development revealed that Foxi2 expression is mainly confined
      to subsets of cells in epithelial structures and particular ducts, in addition to
      the developing forebrain and neural retina. Since FoxI factors are thought to be
      implicated in the regulation of cell fate, the highly restricted expression
      pattern of Foxi2 suggestive of a possible role in controlling cellular identity.

PMID- 16289365
TI  - Dendroaspis natriuretic peptide protects the post-ischemic myocardial injury.
AB  - The present study used isolated rat hearts to investigate whether (1) Dendroaspis
      natriuretic peptide (DNP) is protective against post-ischemic myocardial
      dysfunction, and (2) whether the cardioprotective effects of DNP is related to
      alteration of Bcl-2 family protein levels. The excised hearts of Sprague-Dawley
      rats were perfused on a Langendorff apparatus with Krebs-Henseleit solution with
      a gas mixture of 95% O2 and 5% CO2. Left ventricular end-diastolic pressure
      (LVEDP, mmHg), left ventricular developed pressure (LVDP, mmHg) and coronary flow
      (CF, ml/min) were continuously monitored. In the presence of 50 nM DNP, all
      hearts were perfused for a total of 100 min consisting of a 20 min pre-ischemic
      period followed by a 30 min global ischemia and 50 min reperfusion. Lactate
      dehydrogenase (LDH) activity in the effluent was measured during reperfusion.
      Treatment with DNP alone improved the pre-ischemic LVEDP and post-ischemic LVEDP
      significantly comparing with the untreated control hearts during reperfusion.
      However, DNP did not affect the LVDP, heart rate (HR, beats/min), and CF. Bcl-2,
      an anti-apoptotic protein expressed in ischemic myocardium of
      DNP+ischemia/reperfusion (I/R) group, was higher than that in I/R alone group.
      Bax, a pro-apoptotic protein expressed in ischemic myocardium of DNP+I/R group,
      has no significant difference compared with I/R alone group. These results
      suggest that the protective effects of DNP against I/R injury would be mediated,
      at least in part, through the increased ratio of Bcl-2 to Bax protein after
      ischemia-reperfusion.

PMID- 16289366
TI  - Identifying the relationship among mental status, functional independence and
      mobility level in Turkish institutionalized elderly: gender differences.
AB  - The purpose of this study was to examine gender differences in older people
      living at a rest home in terms of functional independence, mental status and
      mobility level and to describe the relationship among the three outcome
      variables. One hundred and thirty-three elderly people (60 women, 73 men), aged
      65 years and above were included in the study. The average age was 75.3 +/- 6.7
      years (range, 65-90 years). Mental status was assessed using the Hodkinson Mental
      Test (HMT). Functional independence was measured using Functional Independence
      Measurement (FIM). Mobility level was evaluated using the Rivermead Mobility
      Index (RMI). Elderly women had lower scores regarding all the outcome variables
      when compared to older men. The older men had higher cognitive performance than
      women. In addition, women were at low level of mobility and depended upon the
      daily living activities (p < 0.05). Both genders showed a significant negative
      correlation between mental status and functional independence or mobility level,
      while the correlation between functional independence and mobility level was
      significantly positive. The data showed that mental impairment decreases both
      functional status and mobility level of the institutionalized elderly people.
      Gender difference was found to be an important factor affecting the outcome
      variables of the study.

PMID- 16289367
TI  - Invasive and non-invasive investigations for non-alcoholic steatohepatitis
      (NASH): The other face of the coin of histology.

PMID- 16289368
TI  - Anti-atherogenic properties of fibrates may be largely due to their anti
      inflammatory effects.
AB  - Current understanding of the pathophysiology of atherosclerosis has undergone a
      remarkable evolution. Compelling evidence has evolved at both the basic science
      and clinical level for the importance of inflammation in the pathogenesis of
      atherosclerosis and its complications. Recent research has shown that both
      systemic and local inflammation plays a central role in all phases of the
      atherosclerotic process. Inflammatory cells dominate early atherosclerotic
      lesions, inflammatory cytokines accelerate progression of the lesions, and
      activation of inflammation can elicit acute coronary syndromes. Robust clinical
      studies have affirmed that fibrates are anti-atherogenic and can improve the
      cardiovascular risk profile. Fibrates not only modulate the serum concentrations
      of triglyceride and cholesterol, but also inhibit systemic inflammatory statue
      and inflammatory response in vascular cells. Fibrates act anti-inflammatory
      effects in monocyte/macrophage, T lymphocyte, endothelial cells, vascular smooth
      muscle cells and adipocytes. Since atherosclerosis is now regarded as an
      inflammatory disease and those inflammatory cells play critical important roles
      in the initiation and development of atherosclerosis, we hypothesize that anti
      atherogenic properties of fibrates may be largely due to their anti-inflammatory
      effects.

PMID- 16289369
TI  - Application of classical molecular dynamics for evaluation of proton transfer
      mechanism on a protein.
AB  - Proton transfer reactions on surfaces are prevalent in biology, chemistry and
      physics. In the present study, we employed classical Molecular Dynamics
      simulations to search for the presence of transient configurations that enable
      proton transfer, or proton sharing, between adjacent carboxylate groups on the
      protein surface. The results demonstrate that, during random fluctuations of the
      residues on the surface, there are repeated situations in which nearby
      carboxylates either share a common proton through a hydrogen bond, or are
      connected by a few water molecules that form conducting networks. These networks
      do not extend out of the common Coulomb cage of the participating residues and
      the lifetimes of the bridged structures are sufficiently long to allow passage of
      a proton between the carboxylates. The detection of domains capable of supporting
      a rapid proton transfer on a protein supports the notion that clusters of
      carboxylates are the operative elements of proton collecting antennae, as in
      bacteriorhodopsin, cytochrome c oxidase or the photosynthetic reaction center.

PMID- 16289370
TI  - The role of lipid rafts in the pathogenesis of bacterial infections.
AB  - Numerous pathogens have evolved mechanisms of co-opting normal host endocytic
      machinery as a means of invading host cells. While numerous pathogens have been
      known to enter cells via traditional clathrin-coated pit endocytosis, a growing
      number of viral and bacterial pathogens have been recognized to invade host cells
      via clustered lipid rafts. This review focuses on several bacterial pathogens
      that have evolved several different mechanisms of co-opting clustered lipid rafts
      to invade host cells. Although these bacteria have diverse clinical presentations
      and many differences in their pathogenesis, they each depend on the integrity of
      clustered lipid rafts for their intracellular survival. Bacterial invasion via
      clustered lipid rafts has been recognized as an important virulence factor for a
      growing number of bacterial pathogens in their battle against host defenses.

PMID- 16289371
TI  - Voltage gating and anions, especially phosphate: a model system.
AB  - The voltage sensor of voltage gated sodium and potassium channels consists of
      four sets of transmembrane segments, of which one, called S4, contains at least
      four arginines; these are presumed to each carry positive charges. The channel
      opening is usually attributed to the outward (i.e., toward the extracellular side
      of the membrane) motion of S4. The evidence for this motion is based on certain
      experiments that appear to show differential access to parts of S4 from the
      intracellular and extracellular sides of the membrane in the open and closed
      states. A newly available structure [S.B. Long, E.B. Campbell and R. MacKinnon,
      Crystal structure of a mammalian voltage-dependent Shaker family K(+) channel.
      Science 309 (2005) 897-903; S.B. Long, E.B. Campbell, R. MacKinnon, Voltage
      sensor of Kv1.2: structural basis of electromechanical coupling. Science 309
      (2005) 903-908][1,2] has now been used to argue for a large scale motion,
      although, as a static structure, it is not conclusive. In this paper, we consider
      the effect of anions in the surrounding medium. Phosphate is present in the
      intracellular as well as the extracellular fluid, apparently at hundreds of
      micromolar concentration, or more. There is evidence in the literature suggesting
      that phosphate-arginine complexes are rather strong. In a recent calculation one
      of us [M.E. Green, A possible role for phosphate in complexing the arginines of
      S4 in voltage gated channels J. Theor. Biol. 233 (2005) 337-341][3] has shown
      that a model peptide with a 2:1 arg:phosphate complex should have a favorable
      geometry. Here, we present NMR evidence of the existence of phosphate complexes
      of a model peptide with two arginines separated by two hydrophobic residues, the
      same spacing as in S4 segments. The complexes (there are different complexes for
      HPO(4)(2-) and for H(2)PO(4)(-) [3]) form with concentrations of peptide in the
      range of hundreds of micromolar, making it significant in the biological context.
      NMR spectra provide changes in chemical shift as functions of both phosphate
      concentration and pH. The resulting curves show titration of the phosphate, with
      its standard pK. Possible implications for other anion-S4 interactions, including
      ion pairs rather than complexes, as with Cl(-), are also discussed.

PMID- 16289372
TI  - Cor triatriatum associated with severe valvular pulmonary stenosis and patent
      ductus arteriosus: an unreported constellation.
AB  - A divided left atrium because of cor triatriatum is a relatively rare cardiac
      anomaly requiring corrective surgery. Although association of cor triatriatum
      with different congenital heart diseases had been reported, to our knowledge, its
      association with severe valvular pulmonary stenosis and patent ductus arteriozus
      had not been reported previously. In this paper, an asymptomatic case with cor
      triatriatum, severe valvular pulmonary stenosis and patent ductus arteriosus is
      defined.

PMID- 16289373
TI  - Reducing cardiovascular risk in diabetes: beyond glycemic and blood pressure
      control.
AB  - Patients with diabetes mellitus have a much higher rate of cardiovascular disease
      (CVD) than the general population, and, in addition to glycaemia and
      hypertension, dyslipidemia has emerged as an important modifiable cardiovascular
      risk factor in these patients. In most patients with type 2 diabetes, the major
      features of dyslipidemia are increased triglyceride levels, decreased high
      density lipoprotein cholesterol (HDL-C) levels, and changes in the composition
      and level of low-density lipoprotein cholesterol (LDL-C). Clinical trials
      evaluating both primary and secondary prevention of CVD demonstrate that lipid
      lowering therapy results in a substantial reduction of cardiovascular risk in
      patients with type 2 diabetes. Low-density lipoprotein cholesterol is the first
      priority for treatment, with a statin in adequate dosage as the first choice for
      pharmacological therapy. The first statin trial conducted solely in patients with
      type 2 diabetes and no prior CVD demonstrated a 37% reduction in cardiovascular
      events in patients randomized to atorvastatin 10 mg compared with placebo.
      Additional trials that further address the benefits of lipid-lowering therapy in
      patients with diabetes are near completion, or are underway, and should provide
      important information about further attenuating risk in patients with diabetes.

PMID- 16289374
TI  - Molecular signatures associated with clinical outcome in patients with high-risk
      head-and-neck squamous cell carcinoma treated by surgery and radiation.
AB  - PURPOSE: The local-regional control rate for advanced head-and-neck squamous cell
      carcinoma (HNSCC) remains poor and is unpredictable for a given individual. This
      study examined whether gene expression patterns developed from tumors from
      surgicopathologic, criteria-defined, high-risk HNSCC patients could be correlated
      with clinical outcomes, namely, metastasis or nonrecurrent disease. METHODS AND
      MATERIALS: Fifteen primary tumors from patients treated with a consistent
      protocol of surgery followed by radiotherapy were examined. Seven of these tumors
      were from high-risk patients who developed distant metastasis (DM), and eight
      tumors were from patients with no recurrence (NR) (median follow-up, 59 months).
      RESULTS: Unsupervised clustering of gene expression did not separate the two
      groups from one another, but when supervised methodologies were applied, 205
      genes discriminated the two groups. Within the DM group, genes associated with
      cell growth and proliferation; DNA replication, recombination, and repair;
      antiapoptotic pathways; cell adhesion; and angiogenesis were identified. For NR
      samples, discriminatory genes were associated with the onset of apoptosis.
      CONCLUSIONS: Our data suggest that gene expression analysis of surgically excised
      HNSCC tumors from patients considered at high risk for recurrence has the
      potential to identify individuals susceptible to metastasis on the basis of
      distinct gene-expression patterns. These patients would be ideal candidates for
      testing systemic therapy.

PMID- 16289375
TI  - Optical coherence tomography for identifying unstable coronary plaque.
AB  - This manuscript examines intravascular imaging with optical coherence tomography
      (OCT). OCT is a potentially attractive intravascular imaging technology due to
      its high resolution, small catheters/guidewires, and ability to be combined with
      spectroscopic techniques. Its potential disadvantages remain its limited
      penetration and signal attenuation by blood. The manuscript reviews unstable
      plaque, OCT principles, historical development, current challenges, and
      comparison with IVUS.

PMID- 16289376
TI  - Chimeric synthetic peptides as antigens for detection of antibodies to
      Trypanosoma cruzi.
AB  - Six chimeric synthetic peptides (QCha-1, QCha-2, QCha-3, QCha-4, QCha-5, and QCha
      6) incorporating antigenic sequences of two immunodominant repeat B-cell epitopes
      of Trypanosoma cruzi were synthesized by conventional solid-phase peptide
      synthesis. The antigenic activity of these peptides was evaluated by
      UltramicroEnzyme-linked immunosorbent assay (UMELISA) by using panels of positive
      Chagasic sera (n=82), while specificity was evaluated with samples from healthy
      blood donors (n=44) and patients with other infectious diseases (n=86). The
      antigenicity of the chimeric peptides in solid-phase immunoassays was compared
      with that of the monomeric peptides. Data demonstrated that the chimeric peptide
      QCha-5 was the most reactive because it detected antibodies to parasite
      efficiently. The results indicate that chimeric peptide as coating antigen is
      very useful for the immunodiagnosis of Chagas' disease.

PMID- 16289377
TI  - Identification of novel steroid target genes through the combination of
      bioinformatics and functional analysis of hormone response elements.
AB  - Steroid hormone receptors including androgen receptor (AR), glucocorticoid
      receptor (GR), progesterone receptor (PR), and mineralocorticoid receptor (MR)
      recognize and bind to identical consensus hormone response elements (HREs), which
      consist of two hexameric half-sites (5'-AGAACA-3') arranged as inverted repeats
      with a 3-bp spacer. Although only a few near-consensus HRE sequences have been
      identified in the transcriptional regulatory regions of known steroid target
      genes, it has been unclear whether the exact consensus sequences function as bona
      fide HREs in vivo. A genome-wide in silico screening of palindromic HREs
      identified 565 exact consensus sequences in human genome (NCBI 35 assembly). In
      this study, of 565 exact consensus elements, functional in vivo receptor binding
      was evaluated regarding 26 sequences located within 10 kb upstream to the 5' end
      of annotated genes through chromatin immunoprecipitation (ChIP) assay using cells
      endogenously expressing steroid hormone receptors. Hormone responsiveness of
      proximal gene expression was examined through quantitative RT-PCR. As far as
      performing ChIP assay for AR, GR, and PR, 14 of 26 elements significantly
      recruited at least one of the receptors by hormone treatment (>2-fold enrichment
      versus vehicle). In terms of gene expression in the vicinity of the above 14
      functional perfect HREs, four genes were upregulated by >2-fold with hormone
      treatment. The present data suggest that the combination of bioinformatics
      analysis and quantitative experimental evaluation is useful to identify novel
      functional HREs that may contribute to the transcriptional regulation of steroid
      target genes.

PMID- 16289378
TI  - Decrease in brain POMC mRNA expression and onset of obesity in guinea pigs
      exposed to 2-chloroethyl ethyl sulfide, a mustard analogue.
AB  - The full spectrum of physiological effects resulting from exposure to sulfur
      mustard and its analogs is currently unknown. In a guinea pig model, initially
      selected to study the role of an inflammatory cytokine cascade in mustard gas
      induced lung injury, we observed significant body weight gain in guinea pigs
      exposed to an intratracheally injected single dose of 2-chloroethyl ethyl
      sulfide, a mustard analog. The body weight gain was not associated with any
      apparent change in appetite. To further elucidate a molecular basis for the
      observed weight gain, we evaluated candidate genes for the obese phenotype by
      quantitative RT-PCR. We observed a time- and dose-dependent decrease in guinea
      pig pro-opiomelanocortin (POMC) message following treatment with mustard gas.
      This reduction in POMC message is consistent with the onset of obesity in the
      animals. We hypothesize that the POMC melanocortin pathway provides a mechanistic
      basis for the observed effects of sulfur mustard on body weight.

PMID- 16289379
TI  - A novel nucleolar protein interacts with ribosomal protein S19.
AB  - The gene encoding ribosomal protein S19 (RPS19) is mutated in approximately 25%
      of patients with Diamond-Blackfan anemia (DBA), which is a rare congenital
      erythroblastopenia. DBA patients have a variety of clinical characteristics, and
      the role of the RPS19 gene in the pathogenesis of the disease is presently
      unknown. To investigate a possible role for RPS19 in erythropoiesis, we looked
      for proteins associated with mouse RPS19 using a yeast two-hybrid system and
      identified a novel protein, which we named S19 binding protein (S19BP). The
      deduced amino acid sequence of S19BP derived from cDNA defines a calculated mass
      of 15,849 and an isoelectric point of 11.3. No known functional motifs were found
      in S19BP except a short polylysine tract embedded in a putative nucleolar
      localization signal. Immunolocalization experiments revealed that S19BP was
      highly concentrated in nucleoli after 6 h of transfection in Cos-7 cells. S19BP
      was expressed ubiquitously at a basal level but a significantly high level of
      expression was observed in some tissues.

PMID- 16289380
TI  - Expression of 5-oxoETE receptor in prostate cancer cells: critical role in
      survival.
AB  - Previously, we reported that metabolism of arachidonic acid through the 5
      lipoxygenase (5-LOX) pathway plays an important role in the survival and growth
      of human prostate cancer cells. Inhibition of 5-LOX by pharmacological inhibitors
      triggers apoptosis in prostate cancer cells within hours of treatment, which is
      prevented by the metabolites of arachidonate 5-lipoxygenase, 5(S)
      hydroxyeicosatetraenoic acid (5(S)-HETE), and its dehydrogenated derivative, 5
      oxoeicosatetraenoic acid (5-oxoETE). These findings suggested that 5-lipoxygenase
      metabolites are critical survival factors of prostate cancer cells. However,
      molecular mechanisms by which 5(S)-HETE and its derivative 5-oxoETE exert their
      effects on prostate cancer cell survival are yet to be understood. Here, we
      report that human prostate cancer cells differentially express a G-protein
      coupled 5-oxoETE receptor (5-oxoER) in them. Blocking expression of 5-oxoER by
      short-interfering RNA (siRNA) significantly reduced the viability of prostate
      cancer cells, suggesting that 5-oxoER is critical for prostate cancer cell
      survival, and that the 5-LOX metabolite, 5-oxoETE, controls survival of prostate
      cancer cells through its own G-protein-coupled receptor, 5-oxoER.

PMID- 16289382
TI  - Stakeholder position paper: aquaculture producer.
AB  - The use of antimicrobials in domestic aquaculture is limited. There are only two
      approved and available antimicrobials for food fish (Terramycin for Fish) and
      Romet-30 and one approved for ornamental fish (nifurpirinol). These
      antimicrobials are only approved to treat specific diseases in specific aquatic
      animal species. Antimicrobial use data, as well as environmental fate information
      and analysis of barriers to transmission, are valuable for assessing qualitative
      or quantitative risk. In the US, the limited availability of antimicrobials and
      use in aquaculture suggests the best quantitative source of antimicrobial use
      information is directly from drug manufacturers.

PMID- 16289381
TI  - beta-Amyloid increases dendritic Ca2+ influx by inhibiting the A-type K+ current
      in hippocampal CA1 pyramidal neurons.
AB  - Accumulation of the beta-amyloid peptide (Abeta) is a primary event in the
      pathogenesis of Alzheimer's disease (AD). However, the mechanisms by which Abeta
      mediates neurotoxicity and initiates the degenerative processes of AD are still
      not clear. Recent evidence shows that voltage-gated K+ channels may be involved
      in Abeta-induced neurodegenerative processes. In particular, a transient A-type
      K+ current, with a linear increase in its density with distance from soma to
      distal dendrites in hippocampal CA1 pyramidal neurons, has been shown to
      contribute to dendritic membrane excitability. Here, I report that Abeta (1-42)
      inhibits the dendritic A-type K+ current in hippocampal CA1 pyramidal neurons,
      and this inhibition causes increases in back-propagating dendritic action
      potential amplitude and associated Ca2+ influx. These results suggest that the
      persistent inhibition of the A-type K+ current resulting from deposition of Abeta
      in dendritic arborization will induce a sustained increase in dendritic Ca2+
      influx and lead to loss of Ca2+ homeostasis. This may be a component of the
      events that cause synaptic failure and initiate neuronal degenerative processes
      in the hippocampus.

PMID- 16289383
TI  - Husbandry practices and health in smallholder dairy farms near Addis Ababa,
      Ethiopia.
AB  - Our study was conducted from November 2001 to April 2002 in the Debre-Zeit area
      (near Addis Ababa), Ethiopia to assess the husbandry practices and to identify
      health constraints in 100 market-oriented smallholder dairy farms. A
      questionnaire survey, farm visit and animal examination were conducted. Thirty
      eight percent of the smallholder farms were owned by women. Women-owned farms had
      more cows (median=3) than men-owned ones. The median herd size (including young
      animals) was four animals per farm. Median age, parity number and daily milk
      production of cows were, respectively, 5 years, 3 and 10l. The housing conditions
      were tie-stall barns for 53% and shades for the rest. About 48% of the herd were
      kept under poor housing conditions; land-resource limitation was mentioned as the
      major problem. Twenty percent of the farms were using hired labour. Mastitis
      (both clinical and subclinical) was the most-frequently encountered disease
      condition (prevalence at herd level 30%) followed by foot-and-leg problems. Farms
      owned by men or using hired labour had higher disease prevalences. The poor
      housing conditions were associated with the observed prevalences of health
      constraints.

PMID- 16289384
TI  - Stakeholder position paper: food animal veterinarian.
AB  - Food animal veterinarians practice in a variety of settings with considerable
      differences between the settings. Due to variability, aggregate data from
      surveillance of antimicrobial use is not very useful to practitioners unless
      correlated information is provided, such as the relative disease status, ages of
      animals, and purpose of use. Of greater utility is use data as it relates to a
      specific farm or production system. Of greater importance to clinical
      practitioners is a meaningful surveillance system that tracks trends in
      antimicrobial resistance in common pathogens causing animal diseases.

PMID- 16289385
TI  - In vitro age-related responses of endothelial cells to breast cancer cell
      addition.
AB  - AIM: The purpose of this study was to determine if the in vitro age of
      endothelial cells alters endothelial response(s) to breast cancer cells. METHOD:
      After characterizing lower passage ("young"; passages 10-16) and higher passage
      ("old"; passages 30-36) bovine pulmonary artery endothelial cells (BPAECs),
      fluorescently labeled MCF-7 breast cancer cells were added to confluent
      monolayers of young and old BPAECs. RESULTS: Transient gaps that peaked in size
      by 12 h and closed by 48h occurred between the young BPAECs, while large
      persistent gaps formed between the old BPAECs. Gap formation did not occur when
      184A1 cells, a non-malignant mammary epithelial cell line, were added in place of
      MCF-7 cells, suggesting that the age-related responses of the endothelial cells
      to MCF-7 cell addition were specific to the tumor cell addition. Additionally,
      more MCF-7 cells migrated through old BPAEC monolayers, than young BPAEC
      monolayers, grown on Matrigel-coated filters. Finally, DNA fragmentation and
      fluorescent annexin-V binding assays suggested increased MCF-7 cell-induced
      apoptosis in older BPAECs, though results from a caspase-3 activation assay were
      equivocal. CONCLUSIONS: In sum, our findings support the notion that aged
      endothelial cells are more susceptible to breast cancer-induced injury, perhaps
      due to increased apoptosis.

PMID- 16289386
TI  - Using a combination of cytochrome P450 1B1 and beta-catenin for early diagnosis
      and prevention of colorectal cancer.
AB  - BACKGROUND: Although fecal occult blood test and invasive endoscopic examination
      are common used to detect colorectal adenomas and cancers, non-invasive and
      specific biomarkers are still under investigation. The objective is to evaluate
      the biomarker CYP1B1 alone or in combination with aryl hydrocarbon receptor
      (AhR), nuclear beta-catenin, p53 or bcl-2 for early diagnosis and prevention of
      colorectal cancer. METHODS: These biomarkers were analyzed semi-quantified across
      231 colonic tissues including 97 adenocarcinomas, 85 adenomas and 49 non
      neoplastic colons using immunohistochemistry. In order to differentiate non
      neoplastic colons from colorectal neoplasms (adenoma and carcinoma), the values
      for CYP1B1, AhR, nuclear beta-catenin, p53 and bcl-2 expressions were subjected
      to discrimination analysis, then the cross-validation, sensitivity and
      specificity of these models were calculated. RESULTS: Expressions of CYP1B1, p53,
      nuclear beta-catenin and bcl-2 were significantly associated with colorectal
      carcinogenesis (p<0.01 for the trend test). The overexpression rates for CYP1B1,
      p53, nuclear beta-catenin and bcl-2 were significantly higher in the adenoma and
      carcinoma groups than in the non-neoplastic colon group (p<0.05). The
      discrimination models showed that a combination of two biomarkers was better than
      a single biomarker, and provided specificity ranging from 39% to 100% and
      sensitivity ranging from 43% to 82% for colorectal carcinoma. CONCLUSIONS: The
      increase in expression of CYP1B1 occurred not only in colorectal carcinoma and
      but also in adenoma. Moreover, a screening panel of CYP1B1 in combination with
      nuclear beta-catenin was the most suitable marker pair to screen for colorectal
      carcinoma based on this study.

PMID- 16289387
TI  - Correlation p53 expression and human papilloma virus deoxyribonucleic acid with
      clinical outcome in early uterine cervical carcinoma.
AB  - BACKGROUND: In the present study we assessed whether expression of p53 protein or
      HPV DNA correlates with recurrence as well as several known prognostic factors in
      uterine cervical carcinoma. METHODS: Forty-nine patients with FIGO stage IA-IIB
      who underwent hysterectomy between 1998 and 2002 were retrospectively studied.
      All 49 cancer tissue samples were used for immunohistochemical study. Twenty-five
      of 49 cases were also examined by PCR-RFLP for detection and typing of HPV DNA.
      RESULTS: Twenty of 49 (40.8%) specimens demonstrated nuclear staining for p53. A
      significant association between p53 overexpression and age, hormonal status, FIGO
      stage, or recurrence was observed (p=0.02, 0.01, 0.03, 0.01). However, no
      significant association was found between p53 overexpression and lymph node
      metastases, parametrium involvement, or risk of death (p=0.18, 0.06, 0.14).
      Nineteen of 25 (76%) were HPV DNA-positive and 6 (24%) were negative. DISCUSSION:
      There was no relation between HPV DNA positivity and age, FIGO stage, lymph node
      metastases, parametrium involvement, recurrence, or risk of death. CONCLUSION:
      p53 overexpression is associated with age, hormonal status, FIGO stage, and
      recurrence in uterine cervical carcinoma.

PMID- 16289388
TI  - Urinary estrogen metabolites, prostate specific antigen, and body mass index
      among African-American men in South Carolina.
AB  - INTRODUCTION: Estrogen metabolites have been linked to risk of breast cancer, and
      we were interested in whether they are associated with prostate specific antigen
      (PSA) and other factors associated with prostate cancer. African-American (AA)
      men in South Carolina have among the highest prostate cancer rates in the world,
      and thus provide an ideal population in which to investigate this hypothesis.
      METHODS: We recruited AA men attending prostate cancer screenings in and around
      Columbia, South Carolina. Because very few men had elevated PSAs, we restricted
      our study to the 77 men whose PSA was below the cutpoint used by the screening
      program to indicate need for diagnostic workup. These men provided spot urine
      samples and answered demographic and lifestyle questions including self-reported
      body weight, height, exercise, tobacco use, medications, cancer history and age.
      Levels of urinary 2-hydroxyestrone (2-OHE1) and 16alpha-hydroxyestrone (16alpha
      OHE1), and their ratio (2/16) and blood PSA levels were determined. RESULTS:
      After adjusting for a statistically significant interaction between age and BMI,
      we found a reduction of 14.2% in 2-OHE1 for each 1.0 ng/ml increase in PSA
      (p=0.05). For obese AA men only (BMI> or =30 kg/m2), 2-OHE1 increased by 36% for
      each decade of age (p=0.009). CONCLUSIONS: Estrogen metabolites may be related to
      PSA level in AA men. Older men with BMIs greater than 30 kg/m2 had an unexpected
      increase in 2-OHE1, suggesting a dysregulation of this estrogen metabolism
      pathway. Further studies of estrogen metabolites may provide insights into
      prostate cancer risk factors.

PMID- 16289389
TI  - Analysis of paired primary lung and lymph node tumor cells: a model of metastatic
      potential by multiple genetic programs.
AB  - BACKGROUND: The current paradigm of metastasis proposes that rare cells within
      primary tumors acquire metastatic capability via sequential mutations, suggesting
      that metastases are genetically dissimilar from their primary tumors. We tested
      this hypothesis by examining the molecular differences, if any, between primary
      tumor cells and matched lymph node metastatic cells in human non-small-cell lung
      carcinoma specimens. METHODS: We performed transcriptional profiling studies on
      malignant cells from 11 pairs of stage III tumors and their tumor-positive lymph
      nodes using multiple, complementary analytic techniques. To confirm the overall
      validity of microarray data, we used real-time polymerase chain reaction.
      RESULTS: The molecular signature of nodal metastasis was a composite of two
      paradoxical, but not mutually exclusive, expression patterns: metastatic cells
      are: (1) different from their primary tumor cells based on a few genes and (2)
      genetically similar, overall, to their primary tumor cells. Consequently, we
      found a 27-gene subset sufficient to differentiate nodal metastatic cells from
      primary tumor cells. CONCLUSIONS: Thus, we concluded that a more accurate model
      of metastatic potential is based on a global primary tumor expression pattern
      along with the appearance of distinct metastatic variants. The 27-gene signature
      differentiating primary tumors from their metastatic cells may define non-small
      cell lung carcinoma nodal metastatic potential.

PMID- 16289390
TI  - Time of Flight-Secondary Ion Mass Spectrometry on isolated extracellular
      fractions and intact biofilms of three species of benthic diatoms.
AB  - Time of Flight-Secondary Ion Mass Spectrometry (ToF-SIMS) was used to study
      compositional characteristics of Extracellular Polymeric Substances (EPS) and
      compared these to characteristics of the EPS-matrix of intact diatom biofilms.
      Three benthic diatoms species were investigated, Cylindrotheca closterium,
      Navicula mutica and Nitzschia cf. brevissima. Comparison of the ToF-SIMS spectra
      of sequentially extracted EPS-fractions by cluster analysis and multidimensional
      scaling analysis (MDS) indicated that soluble and bound EPS were not
      distinguishable based on their ion spectra. On the contrary the water insoluble
      bicarbonate soluble (WIBS)-EPS-fraction formed a distinct cluster showing that
      this material was compositionally different from the other EPS-fractions. Ion
      spectra of the EPS-fractions were dissimilar to results obtained from intact
      biofilms. This suggested that during the extraction procedure, the structure of
      the EPS irreversibly changed, which alters the fragmentation patterns of the
      extracellular surface layer. Furthermore, from the examination of the positive
      ion spectra it was shown that the overall composition of EPS in the intact
      biofilms was different between diatom species. In spite of these differences,
      several common peak patterns were shared between different species. This suggests
      the presence of common structural components in the EPS of these diatoms that may
      play a role in building the surface EPS-layer.

PMID- 16289391
TI  - Comparison of methods and animal models commonly used for investigation of fecal
      microbiota: effects of time, host and gender.
AB  - Denaturing gradient gel electrophoresis (DGGE), terminal restriction fragment
      length polymorphism (T-RFLP) and plating on selective agars were used to study
      variation in the fecal microbiota of rats over time as well as variation between
      individuals. Investigated rats were either conventional and specific pathogen
      free (SPF), or human flora associated (HFA). A higher variation (p<0.05) in fecal
      microbiota over time was observed for HFA than for SPF animals. Analysis of DGGE
      and T-RFLP profiles of fecal microbiota from SPF and HFA rats revealed that
      variation over time was less significant than variation between individuals, and
      that phylogenetic profiles clustered according to gender. These observations
      should be taken into account when designing future research addressing changes in
      fecal microbiota.

PMID- 16289392
TI  - The evolution of peptide deformylase as a target: contribution of biochemistry,
      genetics and genomics.
AB  - Although peptide deformylase (PDF, EC 3.5.1.27) was first described in 1968, the
      instability of enzyme preparations prevented it from being seriously considered
      as a target until this problem was finally solved in 1998. PDFs essentiality was
      first demonstrated in Escherichia coli in 1994. Genomic analyses have shown this
      enzyme to be present in all eubacteria. PDF homologs have also been found in
      eukaryotes including Homo sapiens. The function and relevance of the human
      chromosomal homolog to the safety of PDF inhibitors as therapeutic agents is not
      clear at this stage. Although there is considerable sequence variation between
      the different bacterial PDFs, there are three strongly conserved motifs that
      together constitute a critical metal binding site. The observation that PDF is a
      metalloenzyme has led to the design of inhibitors containing metal chelating
      pharmacophores. The most potent of these synthetic inhibitors are active against
      a range of clinically relevant respiratory tract pathogens in vitro and in vivo,
      including those resistant to current antibiotics. Mutants resistant to PDF
      inhibitors have been obtained in the laboratory; these resulted from mutations in
      the genes for transformylase (EC 2.1.2.9) or PDF. The mechanism involved and its
      frequency were pathogen-dependent. The two most advanced PDF inhibitor leads,
      which are both reverse hydroxamates, have progressed to phase 1 clinical trials
      and were well tolerated.

PMID- 16289393
TI  - Natural products--the future scaffolds for novel antibiotics?
AB  - Natural products have played a pivotal role in antibiotic drug discovery with
      most antibacterial drugs being derived from a natural product or natural product
      lead. However, the rapid onset of resistance to most antibacterial drugs
      diminishes their effectiveness considerably and necessitates a constant supply of
      new antibiotics for effective treatment of infections. The natural product
      templates of actinonin, pleuromutilin, ramoplanin and tiacumicin B, which are
      compounds undergoing clinical evaluation, represent templates not found in
      currently marketed antibacterial drugs. In addition, the new templates present in
      the recently discovered lead antibacterials arylomycin, GE23077, mannopeptimycin,
      muraymycin/caprazamycin, nocathiacin and ECO-0501, are discussed. Despite
      extensive efforts to identify antibiotic leads from molecular targets, only the
      peptide deformylase inhibitor LBM-415 is currently in clinical trials. It is
      proposed that new antibacterial assays which combine cell-based screening with
      molecular targets could offer better prospects for lead discovery.

PMID- 16289395
TI  - To engineer is to create: the link between engineering and regeneration.
AB  - Tissue engineering is a radically different approach to reconstruction of the
      body following degenerative diseases, trauma or chronic debilitating conditions.
      Although there have been some successes, tissue engineering is not yet delivering
      significant progress in terms of clinical outcomes and commercialization. Part of
      the problem is that we have failed to understand what tissue engineering really
      means and to appreciate that engineering is synonymous with creation. These
      processes involve many different phases and there has been minimal integration of
      these phases within tissue-engineering paradigms. The conventional concept, based
      upon a temporal sequence from sourcing cells through to the incorporation of
      generated tissue into a host, has to be transformed by a systems engineering
      approach in which all biological and technological phases, and the inter
      relationships between them, are fully integrated. It might be that real success
      will not be achieved until systems biology is superimposed onto this systems
      engineering paradigm.

PMID- 16289394
TI  - Development of a microtiter plate-based method for determination of degradation
      profile of nitrophenolic compounds.
AB  - A microtiter plate-based assay was developed for the automatic monitoring of
      degradation profile of the yellow-coloured nitrophenolic compounds. The method
      enables to reduce the intervals between measurements of substrate concentration
      to minutes and to overcome the problem of discontinuity of sampling typical for
      conventional methods. The concentrations of nitrophenolic compounds were
      calculated from the absorbance values determined automatically by BIOSCREEN C.
      Verification of the method was based on the comparison of results with the
      conventional HPLC method results. The values of the rate and saturation constants
      were comparable for both the microtiter plate-based assay and the conventional
      HPLC method. The automatic method described here seems to be efficient for the
      screening degradation studies, which requires the treatment of quantity of
      samples.

PMID- 16289396
TI  - Effects of motivational interviewing training on mental health therapist
      behavior.
AB  - This study examined the effectiveness of training community mental health
      therapists in motivational interviewing (MI) adapted to treat clients with co
      occurring disorders. Ten therapists with high caseloads of culturally diverse
      clients in two different community mental health settings fulfilled all study
      requirements. MI training consisted of a two-day didactic and experiential
      workshop followed by eight biweekly small group supervision (coaching) sessions.
      Using an interrupted time series design, 156 randomly selected therapy sessions
      involving 28 clients were coded for assessment of therapist fidelity to MI at
      multiple points in time, both pre- and post-training. Employing hierarchical
      linear modeling analysis, significant improvement in MI skill was observed after
      training on five of six key therapist ratings, and on the sole client rating
      (client change talk) that was examined. Importantly, the present study
      demonstrates training-related proficiency in motivational interviewing using: (a)
      a representative sample of mental health therapists from the community; (b) a
      protocol emphasizing adherence to a mental health treatment regimen as well as
      management of substance use behavior for clients with co-occurring disorders; (c)
      repeated random observations of therapy sessions; (d) measurement of training
      related changes in clinician skills and self motivational statements by clients.
      Findings of this effectiveness study compared favorably with efficacy literature
      on MI training.

PMID- 16289397
TI  - Cortical gamma-aminobutyric acid levels and the recovery from ethanol dependence:
      preliminary evidence of modification by cigarette smoking.
AB  - BACKGROUND: Gamma-aminobutyric acid (GABA)ergic adaptations contribute to the
      neurobiology of ethanol dependence and withdrawal. Clinical data suggest that
      tobacco smoking attenuates alcohol withdrawal symptoms. This study's objective
      was to measure time-dependent cortical GABA levels with sobriety in ethanol
      dependent patients with mild to moderate withdrawal severity, controlling for
      alcoholism-related neurotoxicity and smoking. METHODS: Proton magnetic resonance
      spectroscopy (MRS) was used to measure occipital cortical N-acetylaspartate
      (NAA), glutamate plus glutamine, and GABA in 12 ethanol-dependent men at
      approximately 1 week and 1 month of medication-free sobriety on an inpatient
      unit. Eight healthy men were studied once. The tissue composition of the MRS
      volume was determined. RESULTS: Adjusting for less white matter in patients, GABA
      differed insignificantly between ethanol-dependent patients (smokers plus
      nonsmokers) and healthy subjects. In early sobriety, nonsmoking patients had more
      GABA than did smoking patients, but by 1 month, GABA decreased in nonsmokers
      without changing in smokers. Smoking was associated with increased glutamate plus
      glutamine in patients and healthy subjects, adjusting for NAA levels.
      CONCLUSIONS: These data do not show that deficits in cortical GABA contribute
      directly to acute ethanol withdrawal. If smoking prevents withdrawal-related
      changes in cortical GABA systems, it may contribute to comorbidity of alcoholism
      and tobacco smoking.

PMID- 16289398
TI  - Re-irradiation of nasopharyngeal carcinoma with intensity-modulated radiotherapy.
AB  - BACKGROUND AND PURPOSE: To evaluate the treatment outcome in patients with
      locally recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated
      radiation therapy (IMRT). MATERIALS AND METHODS: Between October 2001 and May
      2004, 31 patients with locally recurrent NPC received re-irradiation using IMRT.
      The rT classification distribution was 3 for rT1, 5 for rT2, 9 for rT3, and 14
      for r T4. Median time from first course of radiotherapy to re-irradiation was 51
      months. IMRT was performed using step-and-shoot method with nine 4-6 MV photon
      fields and median prescribed dose was 54 Gy (range: 50-60 Gy). Additional
      treatments included cisplatin-based induction chemotherapy in 68% and
      radiosurgery boost with a single dose which ranged from 8.5 to 12.5 Gy in 32%.
      Median follow-up time was 11 months. RESULTS: After re irradiation, 58% of
      patients had complete regression of primary tumor. One-year loco-regional
      progression-free, distant metastasis-free and overall survival rates were 56, 90,
      and 63%, respectively. Significantly better 1-year local progression-free rate
      was observed in rT1-3 than r T4 tumor (100 vs. 35%). Grade 3 late toxicities,
      mostly ototoxicity/cranial neuropathy, occurred in six patients (19%). One-year
      actuarial rates of late toxicities were 70% for all grades and 25% for Grade 3.
      CONCLUSION: Our preliminary results showed that good control of rT1-3 NPC can be
      achieved using IMRT with a dose between 50 and 60 Gy, whereas the outcome for r
      T4 tumor remained poor. Late toxicities were common but incidence of severe
      toxicities was relatively low.

PMID- 16289399
TI  - Measurement of prostate rotation during insertion of needles for brachytherapy.
AB  - BACKGROUND AND PURPOSE: The purpose of this study is to investigate whether
      prostate rotation due to needle insertion for prostate brachytherapy is
      predictable and if so, to quantify this rotation, and to see whether locking
      needles reduce the magnitude of prostate rotation. PATIENTS AND METHODS: The
      measurements are done at the beginning of the procedure for brachytherapy with a
      Foley catheter in situ. After a needle is inserted into the prostate, a 3D
      ultrasound scan is made. Then the seeds are delivered using RAPID Strands
      (Oncura), and the needle is withdrawn. A second 3D scan is made. The needle and
      seed positions are determined in these scans. To determine the rotation of the
      prostate, the angle between the needle and the seed trajectory is calculated.
      RESULTS: The prostate rotations have been measured in 16 patients, eight without
      the use of locking needles and eight with locking needles. In total 62 needles
      were inserted. The maximum rotation was 13.8 degrees and occurred in the coronal
      plane when no locking needles were used with a significant correlation (P<0.01,
      R=0.637) between the place of insertion and rotation. It was shown that the
      method (with or without locking needles) had a significant (P<0.001) influence on
      the rotation in the coronal plane. Rotations in the sagittal plane ranged from 
      8.5 degrees to +10.2 degrees without correlation with the insertion point of the
      needle or the use of locking needles. CONCLUSIONS: This study showed that
      prostate rotation during needle insertion for prostate brachytherapy is
      relatively large and unpredictable. Locking needles reduce prostate rotation in
      the coronal plane, but not in the sagittal plane. Minimising this rotation is
      necessary for accurate seed delivery, especially when a robotic implantation
      technique is used.

PMID- 16289400
TI  - Identification of Streptococcus spp. causing bovine mastitis by PCR-RFLP of 16S
      23S ribosomal DNA.
AB  - Traditional microbiological methods for identification of Streptococcus spp.
      causing bovine mastitis have been demonstrated to be less than highly reliable.
      PCR-RFLP analysis of 16S-23S ribosomal DNA was used to characterise seven
      reference strains of streptococcal mastitis pathogens as well as four reference
      strains of other gram-positive, catalase-negative cocci of bovine origin to allow
      comparative identification of field isolates. RFLP analysis of PCR products,
      using a combination of two restriction endonucleases in single reactions (HaeIII
      and AluI, HaeIII and RsaI or AluI and RsaI) generated unique patterns for species
      of Streptococcus, Enterococcus and Lactococcus. One hundred field isolates of
      Streptococcus spp. collected from cows with clinical or subclinical mastitis were
      tested. Fifty-seven isolates, classified by conventional tests as S. uberis, were
      identified as 47 S. uberis and six S. parauberis by their unique RFLP patterns.
      The remaining four isolates had RFLP patterns distinct from the reference strains
      and two of these were identified as closely related to S. iniae and two to
      Aerococcus viridans by 16S rRNA sequencing. Conventional identification of 17 S.
      agalactiae and 26 S. dysgalactiae subsp. dysgalactiae was confirmed by RFLP. Use
      of a combination of restriction enzymes in a single tube enabled the rapid,
      accurate, cost effective and easily performed identification of all major
      streptococcal mastitis pathogens.

PMID- 16289401
TI  - Intracellular and current source density analyses of somatosensory input to the
      optic tectum of the frog.
AB  - This is the first report of current source density (CSD) and intracellular
      analyses of non-optic processing in the frog optic tectum. Sciatic nerve
      stimulation was used to test for somatosensory input to the optic tectum. To
      demonstrate the distribution of somatosensory input, field potentials were
      recorded from the whole surface of both tecta. Two components were observed. An
      early component was found in the whole area, but a late component was detected
      only in medial and caudal regions of the contralateral tectum. The effect of
      different stimulus intensity suggested that the optic tectum receives mainly the
      tactile sensation with fast conducting, low threshold level afferents from the
      sciatic nerve. The result of CSD analysis suggests that somatosensory afferents
      terminate on the tectal neurons with vertically expanding dendrites at the medial
      site of the contralateral optic tectum where the late component was found.
      Intracellular recordings demonstrated postsynaptic potentials in the middle and
      deeper layers, which is consistent with results from mammalian superior
      colliculus in earlier studies. Additional stimulation of the optic tract
      demonstrated that some somatosensory neurons had bimodal responses. The responses
      of those in the middle layers appeared to participate in avoidance behavior,
      based upon previous CSD analysis of the tectum using optic tract stimulation. All
      somatosensory responses elicited in these neurons were IPSPs. The findings imply
      that the somatosensory input to the optic tectum gives a suppressive effect on
      avoidance behavior. A somatosensory effect on prey-catching behavior could not be
      found in the present small number of intracellular data.

PMID- 16289402
TI  - Neuronal localization of Ca(v)1.2 L-type calcium channels in the rat basolateral
      amygdala.
AB  - L-type high-voltage-activated calcium channels are involved in the conduction and
      integration of electrical activity and associative long-term potentiation in the
      basolateral amygdalar complex (BLC). However, little is known about the neuronal
      localization of these channels in this brain region. We used immunohistochemical
      techniques to determine which cell types in the BLC express the Ca(v)1.2 subtype
      of L-type calcium channels. Immunofluorescence experiments demonstrated that
      Ca(v)1.2 calcium channels were mainly found in somata and dendrites of pyramidal
      neurons that exhibited immunoreactivity for calcium/calmodulin-dependent protein
      kinase II (CaMK). Only a few parvalbumin-positive and calretinin-positive
      interneurons exhibited Ca(v)1.2 immunoreactivity. The presence of high levels of
      Ca(v)1.2 immunoreactivity in BLC pyramidal cells is consistent with physiological
      findings showing that calcium entry through L-type calcium channels in pyramidal
      cell dendrites in the lateral amygdala is required for associative LTP and the
      conversion of synaptic events into long-term emotional memory.

PMID- 16289403
TI  - Electroacupuncture regulates NMDA receptor NR1 subunit expression via PI3-K
      pathway in a rat model of cerebral ischemia-reperfusion.
AB  - Cell survival is regulated by the balance between death and survival signals.
      Previous studies have shown that the N-methyl-d-aspartate receptors (NMDARs) are
      responsible for the glutamate-induced excitotoxicity in the postischemic brain.
      Meanwhile, nerve growth factor (NGF) is critically involved in cell survival and
      neuroprotective effects via the extracellular signal-related kinase (ERK) pathway
      or the phosphatidylinositol 3-kinase (PI3-K) pathway mediated by the high
      affinity NGF receptor, tropomyosin-related kinase A (TrkA). Clinically,
      electroacupuncture (EA) has been shown to produce beneficial effects on stroke
      patients. However, the detailed mechanisms mediating the beneficial effects of EA
      on stroke are still unknown. In the present study, we found that EA treatment
      reversed the high expression of NR1 subunit and up-regulated the level of TrkA in
      a rat model of middle cerebral artery occlusion. Using protein kinase inhibitors
      of specific intracellular signaling pathways, we found that the neuroprotective
      effects of EA appear to be mediated by stimulation of the PI3-K pathway, but not
      ERK pathway. These findings may provide important experimental evidence for the
      clinical application of EA treatment for stroke patients.

PMID- 16289404
TI  - Morphine tolerance does not develop in mice treated with endothelin-A receptor
      antagonists.
AB  - Long-term use of morphine leads to development of antinociceptive tolerance. We
      provide evidence that central endothelin (ET) mechanisms are involved in
      development of morphine tolerance. In the present study, we investigated the
      effect of ET(A) receptor antagonists, BQ123 and BMS182874, on morphine
      antinociception and tolerance in mice. Mechanism of interaction of ET(A) receptor
      antagonists with morphine was investigated. BQ123 (3 microg, i.c.v.) and
      BMS182874 (50 microg, i.c.v.) significantly enhanced antinociceptive effect of
      morphine (P < 0.05), through an opioid-mediated effect. Treatment with a single
      dose of BQ123 (3 microg, i.c.v.) reversed tolerance to morphine antinociception
      in morphine-tolerant mice. BQ123 or BMS182874 did not affect naloxone binding in
      the brain. Therefore, ET(A) receptor antagonists did not bind directly to opioid
      receptors. [35S]GTPgammaS binding was stimulated by morphine and ET-1 in non
      tolerant mice. Morphine- and ET-1-induced GTP stimulation was significantly lower
      (P < 0.05) in morphine-tolerant group (33% and 42%, respectively) compared to
      control group. BQ123 and BMS182874 did not activate binding in non-tolerant mice.
      BQ123 and BMS182874 significantly increased G protein activation in morphine
      tolerant mice (96% and 86%, respectively; P < 0.05). These results provide
      evidence that uncoupling of G protein occurs in morphine-tolerant mice, and ET(A)
      antagonists promote coupling of G protein to its receptors, thereby restoring
      antinociceptive effect. These findings indicate that ET(A) receptor antagonists
      potentiate morphine antinociception and reverse antinociceptive tolerance in
      mice, through their ability to couple G proteins to opioid receptors.

PMID- 16289405
TI  - Development of a molecular detection and differentiation system for ochratoxin A
      producing Penicillium species and its application to analyse the occurrence of
      Penicillium nordicum in cured meats.
AB  - A PCR method for differentiation and detection of the two known ochratoxin A
      producing Penicillium species, Penicillium verrucosum and Penicillium nordicum
      has been developed. It is based upon two genes of the ochratoxin A biosynthetic
      pathway, namely the ochratoxin A polyketide synthase gene (otapksPN) and a non
      ribosomal peptide syntethase gene (otanpsPN) from P. nordicum. Both ochratoxin A
      producing Penicillia differ characteristically in the PCR result, making a
      taxonomic differentiation possible. P. verrucosum gives consistently only a
      positive reaction with the primers for the otanpsPN gene, whereas P. nordicum is
      positive for both genes. The PCR reaction is negative with all of other food
      related fungal species tested. This PCR system has been used to analyse 62
      Penicillium strains isolated from cured meat products or ripening rooms, the
      natural habitat of P. nordicum. Among the 62 analysed strains 11 (18%) were
      positive with all specific PCR reactions. All 11 strains were able to produce
      ochratoxin A. In a RAPD analysis performed in parallel all 11 strains showed a
      pattern characteristic of P. nordicum, indicating the congruence of all data.
      None of the other strains isolated from cured meat produced ochratoxin A; most of
      them (30 out of 62) had a RAPD pattern characteristic for Penicillium
      nalgiovense. Interestingly some of the P. nalgiovense strains showed weak PCR
      product bands with varying length after electrophoresis. This was true for both
      primer pairs. None of these P. nalgiovense strains however produced detectable
      amounts of ochratoxin A. A more detailed analysis revealed that P. nalgiovense
      carries similar but non-transcribed sequences to the ochratoxin A biosynthetic
      genes of P. nordicum.

PMID- 16289406
TI  - Antibiotic resistance in food lactic acid bacteria--a review.
AB  - Antibiotics are a major tool utilized by the health care industry to fight
      bacterial infections; however, bacteria are highly adaptable creatures and are
      capable of developing resistance to antibiotics. Consequently, decades of
      antibiotic use, or rather misuse, have resulted in bacterial resistance to many
      modern antibiotics. This antibiotic resistance can cause significant danger and
      suffering for many people with common bacterial infections, those once easily
      treated with antibiotics. For several decades studies on selection and
      dissemination of antibiotic resistance have focused mainly on clinically relevant
      species. However, recently many investigators have speculated that commensal
      bacteria including lactic acid bacteria (LAB) may act as reservoirs of antibiotic
      resistance genes similar to those found in human pathogens. The main threat
      associated with these bacteria is that they can transfer resistance genes to
      pathogenic bacteria. Genes conferring resistance to tetracycline, erythromycin
      and vancomycin have been detected and characterized in Lactococcus lactis,
      Enterococci and, recently, in Lactobacillus species isolated from fermented meat
      and milk products. A number of initiatives have been recently launched by various
      organizations across the globe to address the biosafety concerns of starter
      cultures and probiotic microorganisms. The studies can lead to better
      understanding of the role played by the dairy starter microorganisms in
      horizontal transfer of antibiotic resistance genes to intestinal microorganisms
      and food-associated pathogenic bacteria.

PMID- 16289407
TI  - OECD validation of the Hershberger assay in Japan: Phase 3. Blind study using
      coded chemicals.
AB  - The Organization for Economic Co-operation and Development (OECD) has initiated
      the development of new guidelines for the screening and testing of potential
      endocrine disrupters. The Hershberger assay is one of the assays selected for
      validation based on the need for in vivo screening to detect androgen agonists or
      antagonists by measuring the response of five sex accessory organs and tissues of
      castrated juvenile male rats: the ventral prostate, the seminal vesicles with
      coagulating glands, the levator ani and bulbocavernosus muscle complex (LABC),
      Cowper's glands, and the glans penis. The Phase 1 feasibility demonstration stage
      of the Hershberger validation program has been successfully completed with a
      single androgen agonist and a single antagonist as reference substances. The
      Phase 2 validation study was performed, employing a range of additional androgen
      agonists and antagonists. Recently, the Phase 3 validation study was conducted
      and performed in several International laboratories. Three Japanese laboratories
      have contributed to the blind study using coded materials of Phase 3 validation.
      Four coded test substances in the agonistic version and seven substances in the
      antagonistic version were orally administered by gavage for 10 consecutive days,
      respectively. In the antagonist version of the assay, 0.2mg/kg/day of
      testosterone propionate (TP) was coadministered by subcutaneous injection. All
      five accessory sex reproductive organs and tissues consistently responded with
      statistically significant changes in weight within a narrow window in both
      versions. Therefore, the Japanese studies support the Hershberger assay as a
      reliable and reproducible screening assay for the detection of androgen agonistic
      and antagonistic effects.

PMID- 16289408
TI  - Quantification of Listeria monocytogenes in salads by real time quantitative PCR.
AB  - A real time quantitative PCR (RTQ-PCR) was carried out purifying DNA extracts of
      Listeria monocytogenes using a High Pure Listeria Sample Preparation Kit and
      quantifying in a LightCycler system with hybridisation probes. A standard curve
      was constructed with serial dilutions. A range linear relationship, from 10 to
      10(5)L. monocytogenes colony forming units (CFU), was observed between threshold
      cycle (Ct) and logarithmic concentration of the serial dilutions. The assay was
      linear in a range from 10 to 10(5)L. monocytogenes CFU and the coefficient of
      determination (r2) was >0.98. RTQ-PCR presented an efficiency of >85%. The
      accuracy of the PCR-based assay, expressed as % bias, ranged from 9% to 26% and
      the precision, expressed as % CV, ranged 9-22%. Intraday and interday
      variabilities were studied at 10(2) CFU/g and resulted in 12% and 14%,
      respectively. The proposed RTQ-PCR method and classical cultural methods were
      applied to analyse 77 salads from restaurants in Valencia (Spain). All culture
      positive samples were also RTQ-PCR positive.

PMID- 16289409
TI  - Japanese encephalitis virus NS2B-NS3 protease binding to phage-displayed human
      brain proteins with the domain of trypsin inhibitor and basic region leucine
      zipper.
AB  - Flavivirus NS2B-NS3 proteases are associated with neurovirulence, becoming an
      important target for insight into the virus-induced pathogenesis. In this study,
      a phage-displayed human brain cDNA library was used to detect possible
      interaction between brain proteins and the Japanese encephalitis virus (JEV) NS2B
      NS3 protease. After six rounds of biopanning, eight high-affinity NS2B-NS3
      protease-interacting phages were identified. Identified NS2B-NS3 protease
      interacting brain proteins contained several repeats of the consensus motifs
      E(R/K)(R/K)K and G(R/K)(R/K) with the dibasic residues, being similar to the
      conserved cleavage sites among flavivirus proteases. In addition, three
      identified brain proteins (phage-24, 34, and 44) were predicted as the domain of
      trypsin inhibitor and basic region leucine zipper (bZIP) using the SMART genome
      search. Immunoprecipitation and cleavage of two brain fusion proteins (phage-24
      and phage-46) by the NS2B-NS3 protease confirmed the specific interaction between
      identified brain proteins and the JEV NS2B-NS3 protease. Fluorogenic peptide
      substrate assays revealed dose-manner inhibitory effects of these two brain
      fusion proteins on the trans-cleavage activity of NS2B-NS3 protease. Moreover, in
      vitro signaling pathway assay revealed that the JEV NS2B-NS3 protease
      significantly inhibited the signaling pathway of activator protein 1(AP1), a
      member of the bZIP family. Our results provide an insight into the protein
      interaction network of the JEV NS2B-NS3 protease in human brain.

PMID- 16289410
TI  - Evaluation of constant current alternating current iontophoresis for transdermal
      drug delivery.
AB  - Previous studies in our laboratory have demonstrated that alternating current
      (AC) iontophoresis can significantly decrease skin electric resistance and
      enhance the transport of charged permeants across skin. Flux variability of
      neutral permeants during AC iontophoresis was also found to be less than that of
      conventional direct current (DC) iontophoresis. The objectives of the present
      study were to evaluate flux enhancement of constant current AC transdermal
      iontophoresis and compare the AC flux with that of constant current DC
      iontophoresis. Iontophoresis studies of AC amplitude of 1, 2, and 5 mA were
      conducted in side-by-side diffusion cells with donor solution of 0.015, 0.15, and
      1.0 M tetraethylammonium (TEA) chloride and receiver solution of phosphate
      buffered saline (PBS) using human epidermal membrane (HEM). Conventional constant
      current DC iontophoresis of 0.2 mA was also performed under similar conditions.
      TEA and mannitol were the model permeants. The following are the major findings
      in the present study. The flux of TEA increased proportionally with the AC
      current for all three TEA chloride concentrations and at the AC frequency used in
      the present study. When the permeant and its counter ion were the only ionic
      species in the donor chamber, the fluxes during DC iontophoresis were weakly
      dependent of its donor concentration. The fluxes of TEA during constant current
      AC iontophoresis were moderately related to the donor concentration with the
      highest TEA flux observed under the 1.0 M TEA chloride condition although the
      relationship between flux and donor concentration was not linear. A trend of
      decreasing electroosmotic transport with increasing donor TEA chloride
      concentration was observed with significant sample-to-sample variability during
      DC iontophoresis. Mannitol permeability was also observed to decrease with
      increasing TEA chloride concentration in the donor under the AC conditions, but
      data variability under AC was significantly smaller than that under DC. The
      results in the present study indicate that constant current AC iontophoresis
      under conditions tolerable to human (2 and 5 mA) can provide predictable fluxes
      that were lower than but of comparable magnitude as those of conventional
      constant current DC iontophoresis (0.2 mA).

PMID- 16289411
TI  - Synthesis of benzylidenated hexopyranosides in ionic liquids.
AB  - The synthesis of 4,6-O-benzylidenated monosaccharides and disaccharides has been
      studied using ionic liquids as a unique solvent alternative. An examination of
      several imidazolium ionic liquids indicates that the benzylidenation of
      hexopyranosides in 3-butyl-1-methylimidazolium tetrafluoroborate, [bmim]BF4,
      gives the highest yields for most of the substrates, and that this solvent system
      could be readily recycled.

PMID- 16289412
TI  - Protective effect of bioactive fraction of Sphaeranthus indicus Linn. against
      cyclophosphamide induced suppression of humoral immunity in mice.
AB  - The bioactive fraction of Sphaeranthus indicus produced dose dependent increase
      in humoral immunity and delayed type hypersensitivity (DTH) response as evidenced
      by increased antibody production and increase in paw edema. The activity at
      higher doses, however, declines. Humoral antibody (HA) titre lowered by
      cyclophosphamide (CP) (p < 0.05) was enhanced by bioactive fraction at doses of
      200 (p < 0.05) and 400 mg/kg (p < 0.001). There was dose dependent increase in HA
      titre in normal as well as immunosuppressed animals indicating that drug is
      effective in humoral immunity. Animals treated with cyclophosphamide and
      receiving bioactive fraction showed significant change in DTH response, which
      directly correlates with cell-mediated immunity, as compared to cyclophosphamide
      alone. Thus, it can be observed that a bioactive fraction of Sphaeranthus indicus
      acts as potentiator of DTH. Furthermore, the HPTLC fingerprint profile of the
      bioactive fraction was established to facilitate its identification and
      characterization. The results suggest that bioactive fraction influences both
      humoral and cell-mediated immunity and offers protection against
      immunosuppression induced by the cytotoxic agent cyclophosphamide.

PMID- 16289413
TI  - Inhibition of inducible nitric oxide synthase by sumaflavone isolated from
      Selaginella tamariscina.
AB  - We previously reported that amentoflavone isolated from Selaginella tamariscina
      inhibits the production of nitric oxide (NO) in macrophages via nuclear factor
      kappaB (NF-kappaB) inactivation. Here, we isolated two other bi-flavonoid
      compounds (sumaflavone and robustaflavone) from Selaginella tamariscina and
      studied their effects on inducible nitric oxide synthase (iNOS) gene expression.
      Sumaflavone inhibited NO production in a concentration-dependent manner and
      blocked the lipopolysaccharide (LPS)-induced expression of iNOS. In contrast,
      robustaflavone only marginally affected iNOS gene expression and NO production.
      To identify the transcriptional factors affected by sumaflavone, we investigated
      NF-kappaB and AP-1 activation. Reporter gene analysis using AP-1-specific
      luciferase reporter and gel shift analysis showed that enhanced AP-1 activity by
      LPS was significantly diminished in macrophages pretreated with sumaflavone.
      However, sumaflavone did not inhibit LPS-inducible NF-kappaB reporter activity.
      Western blot analyses also confirmed that the extent of I-kappaBalpha
      phosphorylation and the nuclear level of p65 were unaffected by sumaflavone.
      These results suggest that the inhibitory effect of sumaflavone on AP-1
      activation may be associated with the potent NO blocking and anti-inflammatory
      effects of Selaginella tamariscina extract.

PMID- 16289414
TI  - Spinal epidural haematoma after blunt trauma to the neck and hyperflection of the
      cervical spine.
AB  - Spinal epidural haematomas (sEDH) can be regarded as rare events, in principle a
      spontaneous and a traumatic aetiology can be distinguished. Spontaneous spinal
      epidural haematomas can arise, e.g. from vascular malformations, coagulopathies,
      etc. On the other hand, traumatic sEDH are related to, e.g. spinal trauma or
      intraoperative vascular injuries. With regard to clinical significance, spinal
      epidural haematomas accompanied by transient mild neurological symptoms up to
      lethal outcomes have been observed. We report on a 53-year-old male alcoholic who
      was found in the kitchen of his asylum in a grotesquely fixed body position, with
      his head and cervical spine in a maximum anteflected position. A general
      practitioner had ruled for a non-natural manner of death due to "broken neck" and
      alcohol intoxication, therefore, the prosecution authorities called for a
      medicolegal autopsy. At autopsy, paravertebral soft tissue haemorrhage in between
      the shoulder blades was disclosed. Furthermore, a spinal epidural haematoma,
      extending from the foramen magnum down to the middle portion of the thoracic
      spine was found. No fractures of vertebrae nor lesions of spine ligaments or
      bleedings of intervertebral discs were found. Blood alcohol concentration was
      determined 1.92 g/l and urine alcohol concentration was 1.76 g/l. Further
      morphological findings were cerebral oedema and cardiac hypertrophy; the urinary
      bladder was found filled to bursting. Neuropathological investigations confirmed
      the presence of the spinal epidural haematoma and assigned lethal significance to
      this finding. There were no histological signs of axonal injury. Reconstruction
      revealed that when sitting on a chair in a drunk condition, the individual's
      upper part of the body had fallen backwards in the corner and subsequently got
      stuck with maximum anteflection of the head and cervical spine, causing rupture
      of vessels and spinal epidural haematoma. Acute respiratory failure caused by
      impairment of the phrenic nerve following spinal epidural haematoma with
      potential synergism of alcohol intoxication was ascertained as the cause of
      death.

PMID- 16289415
TI  - Attenuation of the effects of physostigmine by hyoscine in guinea-pig brain
      cholinergic enzymes: acetylcholinesterase.

PMID- 16289416
TI  - Molecular basis of interactions of cholinesterases with tight binding inhibitors.
AB  - Among the large variety of reversible inhibitors that bind to cholinesterases
      (ChE), only a few exhibit exquisitely strong binding reflected in low femtomolar
      to picomolar equilibrium dissociation constants. These tight binding inhibitors
      owe their high affinity to distinctive modes of interaction with the enzyme:
      naturally occurring snake toxins, the fasciculins, share a large 1000 angstroms2
      complementary surface for its complex with acetylcholinesterases (AChE; EC
      3.1.1.7); transition state analogs trifluoroacetophenones form a covalent bond
      with the active serine; disubstituted 1,2,3-triazole inhibitors formed in situ
      are selected by AChE for optimal interaction surface over the length of the
      active center gorge. All these inhibitors bind with higher affinity to AChEs than
      to the closely related butyrylcholinesterases (BuChE; EC 3.1.1.8). Selectivity of
      individual inhibitors towards BuChE increases with increasing their molecular
      size. Interaction kinetics for all three classes of compounds reveal very slow
      rates of dissociation of the AChE-inhibitor complexes or conjugates combined with
      very fast association rates. The influence of conformational flexibility of the
      active center gorge on the affinity of inhibitor binding was demonstrated by
      comparing binding properties of a series of disubstituted 1,2,3-triazoles having
      systematically varied structures. Analysis of the linear free energy
      relationships of binding to both mouse and Electrophorus AChE reveals independent
      contributions of individual structural elements of inhibitors to their binding
      with the triazole ring emerging as an independently contributing pharmacophore.
      These tight binding inhibitor interactions reveal useful information not only on
      the conformational flexibility of ChEs, but also on the diversity of modes of
      interaction that achieve inhibition.

PMID- 16289417
TI  - Targeting acetylcholinesterase to the neuromuscular synapse.
AB  - The collagen-tailed form of acetylcholinesterase (ColQ-AChE) is the major if not
      unique form of the enzyme associated with the specialized synaptic basal lamina
      at the neuromuscular junction (NMJ). This enzyme form consists of both catalytic
      and non-catalytic subunits encoded by separate genes, assembled as three
      enzymatic tetramers attached to the three-stranded collagen-like tail. We have
      previously shown that catalytic subunits are assembled in the rough endoplasmic
      reticulum and that after approximately 90min a subset of these tetramers assemble
      with collagenic tail subunits in the Golgi apparatus. In muscle, blocking ER to
      Golgi transport with Brefeldin A prevents the appearance of ColQ-AChE, consistent
      with assembly of asymmetric forms in the Golgi. Moreover, newly synthesized and
      assembled ColQ-AChE associates with perlecan intracellularly and can only be co
      immunoprecipitated with anti-perlecan antibodies 90min after the first appearance
      of catalytic subunits. Once assembled, the ColQ-AChE/perlecan complex is
      externalized where it co-localizes with other components of the NMJ including
      dystroglycan, rapsyn, laminin and MuSK. These clusters tend to form over the
      nuclei that are expressing the components, suggesting local vectorial transport
      to the cell surface, and may form a primary scaffold that in turn can capture
      other molecular constituents of the neuromuscular synapse. While most AChE
      clusters on quail myotubes are devoid of acetylcholine receptors, treatment of
      the culture with recombinant agrin results in a rapid translocation of receptors
      to the AChE clusters in less than 4h. It remains to be determined if MuSK is
      localized to the clusters. In vivo, AChE transcripts and enzyme are more highly
      expressed at the NMJs, implying higher rates of AChE translation and assembly in
      the synaptic regions, and hence more ColQ-AChE for localized export. We have
      previously shown that binding sites for ColQ-AChE are concentrated at sites of
      nerve-muscle contact where they colocalize with AChR and perlecan. ColQ-AChE
      binds directly to perlecan using solid phase microtiter plate assay, the Biacore
      assay, and co-immunoprecipitations. Moreover, perlecan binds to dystroglycan at
      the NMJ. In perlecan or dystroglycan null mice there is no accumulation of AChE
      at the NMJ, supporting the hypothesis that this heparan sulfate proteoglycan is
      an essential component of the ColQ-AChE localization mechanism. Together, these
      studies suggest a model of synaptic development whereby AChE can be targeted to
      and clustered on the muscle membrane together with dystroglycan and perlecan to
      form scaffolds to which AChR can be clustered through activation of the MuSK
      receptor. At mature synapses ColQ-AChE is secreted directly into the synaptic
      cleft where it binds to the heparan sulfate proteoglycan perlecan as well as
      potentially other molecules including MuSK, as was recently reported.

PMID- 16289418
TI  - Mcl-1 overexpression in hepatocellular carcinoma: a potential target for
      antisense therapy.
AB  - BACKGROUND/AIMS: Recently, the anti-apoptotic Mcl-1 protein has been reported as
      a resistance factor in various types of cancer. Here we investigated the presence
      of Mcl-1 protein in hepatocellular carcinoma (HCC) tissues and its potential role
      as a molecular drug target for HCC therapy. METHODS: HCC specimens of 149
      patients were examined by immunohistochemistry for Mcl-1 expression. Antisense
      oligonucleotides (ASO) targeting Mcl-1 were evaluated as monotherapy and in
      combination with cisplatin in the HCC cell lines HepG2 and Snu398. Protein
      regulation, cell viability, and apoptosis were assessed by western blotting, cell
      counting, and FACS analysis. RESULTS: Mcl-1 protein is overexpressed in 51% of
      all cases irrespective of underlying disease. Targeting Mcl-1 by ASO specifically
      downregulated Mcl-1 protein expression and led to significant dose and time
      dependent single agent activity in HCC cells characterized by increased apoptosis
      and decreased cell viability. No significant target regulation or cell death was
      observed for control oligonucleotide treatment. Upon combination with cisplatin,
      Mcl-1 ASO revealed a significant chemosensitizing effect. CONCLUSIONS: Mcl-1 is
      overexpressed in half of HCC-tissues. ASO targeting Mcl-1 revealed a prominent
      single agent and chemosensitizing activity against HCC in vitro. Targeting Mcl-1
      might qualify as a promising novel approach in HCC therapy.

PMID- 16289420
TI  - Local and systemic drug competition in drug-eluting stent tissue deposition
      properties.
AB  - The efficacy of drug-eluting stents (DES) requires delivery of potent compounds
      directly to the underlying arterial tissue. The commercially available DES drugs
      rapamycin and paclitaxel bind specifically to their respective therapeutic
      targets, FKBP12 and polymerized microtubules, while also associating in a more
      general manner with other tissue elements. As it is binding that provides
      biological effect the question arises as to whether other locally released or
      systemically circulating drugs can displace DES drugs from their tissue binding
      domains. Specific and general binding sites for both drugs are distributed across
      the media and adventitia with higher specific binding associated with the higher
      specific binding site densities in the media. The ability of rapamycin and
      paclitaxel to compete for specific protein binding and general tissue deposition
      was assessed for both compounds simultaneously and in the presence of other
      commonly administered cardiac drugs. Drugs classically used to treat standard
      cardiovascular diseases, such as hypertension and hypercoaguability, displace
      rapamycin and paclitaxel from general binding sites, possibly decreasing tissue
      reserve capacity for locally delivered drugs. Paclitaxel and rapamycin do not
      affect the other's binding to their biologically relevant specific protein
      targets, but can generally displace each other from tissue at three log order
      molar excess, decreasing arterials loads by greater than 50%. Local competitive
      binding therefore should not limit the placement of rapamycin and paclitaxel
      eluting stents in close proximity.

PMID- 16289419
TI  - Controlled release of paclitaxel from photocrosslinked chitosan hydrogels and its
      subsequent effect on subcutaneous tumor growth in mice.
AB  - A photocrosslinkable chitosan (Az-CH-LA) aqueous solution containing paclitaxel
      resulted in an insoluble hydrogel within 30 s of ultrtaviolet light (UV)
      irradiation. About 35-40% of the paclitaxel was released from the paclitaxel
      incorporated chitosan hydrogel into phosphate buffered saline (PBS) within 1 day,
      after which gradual release occurred during 3 days under in vitro non-degradation
      conditions of the hydrogel. The paclitaxel remaining in the chitosan hydrogel
      retained its biological activity in vitro for at least 21 days, and was released
      from the chitosan hydrogel in vivo upon degradation of the hydrogel. The
      paclitaxel-incorporated Az-CH-LA hydrogel inhibited the growth of subcutaneously
      induced tumors with Lewis lung cancer (3LL) cells more effectively than those
      treated with only Az-CH-LA, only paclitaxel, and a non-treated group (control)
      for at least 11 days. Furthermore, paclitaxel-incorporated chitosan hydrogel
      markedly reduced the number of CD34-positive vessels in subcutaneous 3LL tumors,
      indicating a strong inhibition of angiogenesis. These results suggested that
      application of paclitaxel-incorporated Az-CH-LA hydrogel has an inhibitory
      activity on angiogenesis and tumor growth.

PMID- 16289421
TI  - Micelle-like nanoparticles of star-branched PEO-PLA copolymers as
      chemotherapeutic carrier.
AB  - Four-armed (star-branched) block copolymers of l-PLA and PEO were synthesized
      using ring opening polymerization with different LA/EO ratio. Micellar aggregates
      were prepared from these block copolymers and characterized. Some surface
      segregation of PEG was found : the extent depends on the state of the material
      (whether it is in film or particle form), as well as on molecular geometry. The
      degradation behavior of star-shaped copolymer was studied over a three week
      period and compared to its linear counterpart. Anti-cancer drugs 5-FU and
      paclitaxel were loaded into the micellar nanoparticles. The drug release profile
      showed that the release of paclitaxel from these polymers could be controlled
      over 2 weeks. The kinetics of drug release for star-branched, tri- and di-block
      copolymers were compared. The micelles from star-shaped branch showed more
      complete release of drug than the diblock copolymers; also, the lower
      hydrodynamic radius of star-shaped polymers may result in better clearance of the
      carrier polymer from the body.

PMID- 16289422
TI  - Block copolymer micelles: preparation, characterization and application in drug
      delivery.
AB  - Block copolymer micelles are generally formed by the self-assembly of either
      amphiphilic or oppositely charged copolymers in aqueous medium. The hydrophilic
      and hydrophobic blocks form the corona and the core of the micelles,
      respectively. The presence of a nonionic water-soluble shell as well as the scale
      (10-100 nm) of polymeric micelles are expected to restrict their uptake by the
      mononuclear phagocyte system and allow for passive targeting of cancerous or
      inflamed tissues through the enhanced permeation and retention effect. Research
      in the field has been increasingly focused on achieving enhanced stability of the
      micellar assembly, prolonged circulation times and controlled release of the drug
      for optimal targeting. With that in mind, our group has developed a range of
      block copolymers for various applications, including amphiphilic micelles for
      passive targeting of chemotherapeutic agents and environment-sensitive micelles
      for the oral delivery of poorly bioavailable compounds. Here, we propose to
      review the innovations in block copolymer synthesis, polymeric micelle
      preparation and characterization, as well as the relevance of these developments
      to the field of biomedical research.

PMID- 16289423
TI  - Safe reconstruction of a large cervico-mediastinal tracheal defect with a
      pectoralis major myocutaneous flap and free costal cartilage grafts.
AB  - A large cervico-mediastinal tracheal defect in a 72-year-old man as a result of
      surgery for thyroid carcinoma with tracheal invasion and mediastinal lymph node
      metastasis was reconstructed using a pectoralis major myocutaneous flap and free
      costal cartilage grafts. The tracheal defect (55 mm x 30 mm) was located at the
      thoracic inlet adjacent to the major mediastinal vessels. Our reconstructive
      procedure was a two-staged surgery. In the first stage, a pectoralis major
      myocutaneous flap was transferred to the neck to provide a well-vascularized
      recipient bed for free costal cartilage grafts and to cover large vessels. Two
      pieces of free costal cartilage were grafted on the pectoralis major myocutaneous
      flap, one for the lateral wall reconstruction and the other prefabricated for the
      anterior wall of the trachea. In the second stage, the re-vascularized cartilage
      graft for the anterior wall of the trachea with overlying skin was rotated onto
      the trough of the remaining trachea and the closure of the tracheal defect was
      completed. We conclude that free cartilage grafts for the reconstruction of a
      large cervico-mediastinal tracheal defect can be safely used when they are
      combined with well-vascularized pectoralis major myocutaneous flaps.

PMID- 16289424
TI  - Correlation between dry eye and rheumatoid arthritis activity.
AB  - PURPOSE: To evaluate the incidence of dry eye in rheumatoid arthritis (RA)
      patients with or without Sjogren syndrome (SS), and to investigate the
      correlation between dry eye and RA activity. DESIGN: Prospective case-control
      study. METHODS: In 72 RA patients, the severity of dry eye was assessed by the
      Schirmer test, tear break-up time, rose bengal staining, and fluorescein
      staining. The RA activity was evaluated by the Lansbury index (LI), which is
      based on the duration of morning stiffness, erythrocyte sedimentation rate (ESR),
      grip strength, and joint score. RESULTS: Ten percent of patients met the Japanese
      criteria for SS. No difference in dry eye tests or LI was observed between SS
      patients and non-SS patients. Even in the non-SS group, 90% of patients were
      diagnosed with probable dry eye. In SS patients, positive correlations were
      observed between LI and Schirmer test (P = .048), ESR and Schirmer test (P =
      .035), ESR and rose bengal staining (P = .001), and grip strength and rose bengal
      staining (P = .047). No such correlations were observed in the non-SS patients.
      CONCLUSIONS: Dry eye is common in RA patients, including those without SS. We
      found that there was a correlation between LI and Schirmer test in RA patients
      with SS, but no correlation when the entire group was analyzed. Dry eye always
      should be taken into consideration regardless of the RA activity, because the
      severity of dry eye is independent of RA activity.

PMID- 16289425
TI  - A case of promiscuity: Agrobacterium's endless hunt for new partners.
AB  - Agrobacterium tumefaciens is a phytopathogenic bacterium that induces the 'crown
      gall' disease in plants by transfer and integration of a segment of its tumor
      inducing (Ti) plasmid DNA into the genome of numerous plant species that
      represent most of the higher plant families. Recently, it has been shown that,
      under laboratory conditions, the host range of Agrobacterium can be extended to
      non-plant eukaryotic organisms. These include yeast, filamentous fungi,
      cultivated mushrooms and human cultured cells. In this article, we present
      Agrobacterium-mediated transformation of non-plant organisms as a source of new
      protocols for genetic transformation, as a unique tool for genomic studies
      (insertional mutagenesis or targeted DNA integration) and as a useful model
      system to study bacterium-host cell interactions. Moreover, better knowledge of
      the DNA-transfer mechanisms from bacteria to eukaryotic organisms can also help
      in understanding horizontal gene transfer--a driving force throughout biological
      evolution.

PMID- 16289426
TI  - Analytical evaluation of HgbA1c, microalbumin, CRP, and RF on Architect ci8200
      integrated system and workflow performance evaluation using computer simulation.
AB  - BACKGROUND: Recently, hemoglobin A1c (HgbA1c), microalbumin (MA), C-reactive
      protein (CRP) and rheumatoid factor (RF) have been introduced on high throughput
      general chemistry system. We evaluated analytical performance of these assays on
      an integrated clinical chemistry and immunoassay analyzer and studied the impact
      of testing these assays on these systems on the overall efficiency of the
      analyzer, via computer simulation. METHODS: The analytical performance was
      measured by determining precision, linearity and correlation of patient sample
      results with in-house testing methodology. MedModel simulation software is used
      to develop simulation model and process efficiency is determined by measuring
      turnaround times and resource utilization. RESULTS: Between-days CVs ranged from
      8.59% for MA to 3.22% for HgbA1c level 1 controls. Less than 2% carryover for all
      4 methods was observed on the integrated analyzer. For HgbA1c on HPLC analyzer,
      the minimum and maximum TAT for a batch of 50 samples was 3.78 and 160 min,
      respectively, while for the integrated system it was 28.2 and 35.1 min,
      respectively. Labor utilization for the 2 processes ranged from 3.21% to 3.75%.
      CONCLUSION: Chemistry module on an integrated system can be used to determine the
      HgbA1c and other serum proteins.

PMID- 16289427
TI  - Pseudohyponatraemia in a patient with obstructive jaundice.
AB  - INTRODUCTION: Pseudohyponatraemia is uncommonly associated with severe
      hypercholesterolaemia. Severe hypercholesterolaemia encountered in obstructive
      jaundice due to an abnormal lipoprotein, lipoprotein X (LpX), may result in
      pseudohyponatraemia. CASE REPORT: We report a case of falsely low sodium
      measurements in a patient with severe hypercholesterolaemia due to obstructive
      liver disease. The pathophysiology, complications and analytical effects of LpX
      are briefly discussed. CONCLUSION: The possibility of pseudohyponatraemia should
      be considered in severely hypercholesterolaemic samples.

PMID- 16289428
TI  - Policy context of the poor progress of the pro-poor policy: a case study on the
      Medical-Aid policy during Kim Dae-jung's government (1998-2002) in the Republic
      of Korea.
AB  - Why did not the Medical-Aid policy for the poor progress as expected during Kim
      Dae-jung's government in the Republic of Korea, despite his pro-egalitarian
      position and his campaign pledge to expand welfare benefits? To answer this
      question, Korea's history was briefly reviewed and summarized in this paper to
      describe "a triple burden". The study presents three major characteristics of the
      policy context that acted as barriers to progress of the Medical-Aid policy: the
      overflowing ideologies against the pro-poor policy, the governance crisis, and
      the immaturity of the civil society. The paper argues that any discussion about
      the health policy processes and consequences must stem from a clear understanding
      of the policy context. The future of pro-poor policies in Korea, such as Medical
      Aid, will greatly depend on how Korean society overcomes these contextual
      barriers. The observed characteristics of the context surrounding the Medical-Aid
      policy can also help us understand, in part, the dynamics of other recently
      introduced health policies in South Korea. Moreover, other countries that share a
      similar historical background and policy context with South Korea can learn
      valuable lessons from Korea's experience.

PMID- 16289429
TI  - Imaging and clinical findings in large endolymphatic duct and sac syndrome.
AB  - OBJECTIVE: Large endolymphatic duct and sac syndrome (LEDS) is known as the most
      common kind of inner ear malformations, which is radiologically detectable.
      Nevertheless, nowadays many questions are not fully cleared and LEDS is
      relatively unknown among general radiologists. The aim of this study was to
      evaluate the incidence of LEDS in the own patient population and to present our
      experiences regarding imaging findings, clinical presentation and follow up.
      MATERIALS AND METHODS: Based on a complete recording of all patients, sent from
      ENT department to radiology, we identified all radiological diagnosed cases of
      inner ear malformations including LEDS and all patients in whom an inner ear
      malformation was clinically suspected. The retrospective study included clinical
      records, HR-CT and MRI performed between 1994 and 2002. RESULTS: Among 169
      patients (338 ear), 17 of patients (median age: 12 years) and 28 ears,
      respectively, had enlarged endolymphatic structures. In 10 patients - 6% - (15
      ears), no other abnormalities were detected, called isolated LEDS, seven patients
      showed additional inner ear abnormalities. One patient showed a labyrinthine
      hemorrhage after sudden hearing loss. Audiometric data revealed sensorineural
      hearing loss in 22 ears, deafness in 5 ears and normal hearing in 1 case of 28
      ears. In 10 (67%) of 15 ears with isolated LEDS, the hearing loss was downward
      fluctuating progressive. Twelve patients (eight with isolated LEDS) had partly
      repeated sudden hearing losses. A trigger for worsening of hearing was found in
      five patients. A correlation between the severity of morphological changes on
      imaging and the degree of hearing disturbances could not be detected. Only four
      young patients underwent a radiological examination within the first or second
      year after onset of hearing loss. Three patients received a cochlear implant.
      CONCLUSIONS: LEDS might be the cause of progressive hearing loss and repeated
      acute hearing losses in children and young adults. Imaging plays an important
      role in making the diagnosis.

PMID- 16289430
TI  - Ultrasonography, computed tomography and magnetic resonance imaging in the
      assessment of pelvic pathology.
AB  - OBJECTIVE: Ultrasound (US) is the primary imaging modality in the investigation
      of pelvic pathology in women however it can be very inaccurate. MRI and CT
      provide a more detailed pelvic examination and hence we compared their accuracies
      with that of ultrasound to find out if these two modalities should be used more
      often. PATIENTS AND METHODS: 136 women who had MRI examination of the pelvis for
      investigation of probable pelvic pathology were studied. Hundred and twenty-five
      of these women had an initial ultrasound scan and 23 had an initial CT.
      Diagnostic accuracy was assessed against histopathology or clinical follow-up.
      RESULTS: Histopathology was available in 127/136 women. Overall 36% of the
      lesions were malignant. The overall accuracy of MRI, US and CT were 97%, 77% and
      87%, respectively. MRI confidently identified the tissue of origin in 94%
      compared to only 66% for US. There was a significant difference in accuracy
      between MRI and US in diagnosing adnexal and uterine pathology. MRI was better
      than CT and US in diagnosing peritoneal metastases whereas CT was superior in
      diagnosing omental infiltration. CONCLUSION: We suggest that all women with a
      pelvic abnormality identified on US or in whom there is a strong clinical
      suspicion of disease should undergo MR pelvic imaging in preference to CT because
      of its better soft tissue resolution and multi-planar capability.

PMID- 16289431
TI  - Ocular delivery using poly(ortho esters).
AB  - Three families of poly(ortho esters) were investigated as a means of delivering 5
      fluorouracil (5-FU), an antiproliferative agent used as an adjunct to glaucoma
      filtering surgery. Release of 5-FU from a crosslinked POE II occurred
      predominantly by diffusion with little weight loss, while release of 5-FU from a
      linear polymer occurred by an erosion-controlled process confined predominantly
      to the surface layers. No ocular biocompatibility studies were carried out. Rate
      of release of 5-FU from POE III, a viscous, injectable material, could be
      controlled by polymer molecular weight and polymer hydrophobicity. Excellent
      biocompatibility was demonstrated in subconjunctival, intravitreal and
      suprachoroidal injections. Polymer lifetime in the various sites investigated was
      between 1 and 3 weeks. The effect of sustained 5-FU release was investigated in
      rabbits that underwent a trabeculectomy and the effectiveness of maintaining low
      intraocular pressure for 1 month demonstrated. Release of 5-FU from POE IV was
      investigated using both solid and viscous, injectable materials. Good control
      over rate of 5-FU release by an erosion-controlled process was achieved from both
      types of formulations. Excellent biocompatibility was demonstrated in
      subconjunctival, intracameral, intravitreal and suprachoroidal injections.
      Lifetimes in the various sites ranged from 5 weeks for subconjunctival injections
      to 3 months for intravitreal injections to more than 6 months for intracameral
      and suprachoroidal injections.

PMID- 16289432
TI  - Transplanting stem cells: potential targets for immune attack. Modulating the
      immune response against embryonic stem cell transplantation.
AB  - The curative promise of stem cells and their descendants for tissue regeneration
      and repair is currently the subject of an intense research effort worldwide. If
      it proves feasible to differentiate stem cells into specific tissues reliably and
      safely, this approach will be invaluable in the treatment of diseases that lead
      to organ degeneration or failure, providing an alternative or supplementary
      source of tissue for transplantation. Embryonic stem (ES) cells are pluripotent
      cells derived from the inner cell mass of a pre-implantation blastocyst that can
      produce all cells and tissues of the foetus. In recent years, several
      laboratories have described the directed differentiation of ES cells into
      multiple mature cell types including: cardiomyocytes; haemopoietic cells;
      hepatocytes; neurones; muscle cells and both endocrine and exocrine cells of the
      pancreas. How the immune system of the host will respond when these ES cell
      derived mature cells are transplanted is ill defined. This review will focus on
      the potential mechanisms that the immune system could use to target ES cell
      derived transplants and how unwanted responses might be prevented.

PMID- 16289433
TI  - Transepithelial and endothelial transport of poly (amidoamine) dendrimers.
AB  - This article summarizes our efforts to evaluate the potential of poly
      (amidoamine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically,
      the permeability of a series of cationic PAMAM-NH2 (G0-G4) dendrimers across Caco
      2 cell monolayers was evaluated as a function of dendrimer generation,
      concentration, and incubation time. The influence of dendrimer surface charge on
      the integrity, paracellular permeability, and viability of Caco-2 cell monolayers
      was monitored by measuring the transepithelial electrical resistance (TEER), 14C
      mannitol permeability, and leakage of lactate dehydrogenase (LDH) enzyme,
      respectively. Microvascular extravasation of PAMAM-NH2 dendrimers in relation to
      their size, molecular weight, and molecular geometry is also discussed. Results
      of these studies show that transepithelial transport and microvascular
      extravasation of PAMAM dendrimers are dependent on their structural features
      including molecular size, molecular geometry, and surface chemistry. These
      results suggest that by optimizing the size and surface charge of PAMAM
      dendrimers, it is possible to develop oral delivery systems based on these
      carriers for targeted drug delivery.

PMID- 16289435
TI  - Topical and systemic drug delivery to the posterior segments.
AB  - The posterior segments of the eye are exquisitely protected from the external
      environment. This poses unique and fairly challenging hurdles for drug delivery.
      It is somewhat dogmatic that topical ocular delivery is insufficient to achieve
      therapeutic drug levels in the posterior segments. However, some drugs are
      currently challenging this dogma. In this review we investigate the constraints
      and challenges of drug delivery to the posterior segment. Additionally, we
      outline several potential absorption pathways that may potentially be exploited
      to deliver drug to the back of the eye. Data on several compounds that achieve
      therapeutic posterior segment concentrations after topical dosing is presented.
      Finally, the issues surrounding systemic delivery to the posterior segment are
      reviewed.

PMID- 16289436
TI  - A colorimetric method for detection and quantification of chlorinating activity
      of hemeperoxidases.
AB  - A method of detecting and assaying the halogenating activity of hemeperoxidases
      using the colored substrate, thionin, is reported here. In the presence of
      suitable amounts of peroxide and chloride, chloroperoxidase chlorinates thionin
      and bleaches the intense color of this substrate. The kinetics was quite similar
      to that of the established monochlorodimedone assay. Therefore, the thionin assay
      can be taken as an index of chlorinating activity. This reaction affords an
      escape from background problems and allows easy processing of large volumes of
      samples.

PMID- 16289434
TI  - Characterization of dendrimers.
AB  - Dendrimers pertain both to the molecular chemistry world for their step by step
      controlled syntheses, and to the polymer world because of their repetitive
      structure made of monomers; thus they benefit from analytical techniques from
      both worlds. This review is a survey of the main analytical techniques used for
      the characterization of the chemical composition, the morphology, the shape, and
      the homogeneity of dendrimers. It includes NMR, IR, Raman, UV-Visible,
      fluorescence, circular dichroism, X-ray diffraction, mass spectrometry, SAXS,
      SANS, Laser Light Scattering, microscopy, SEC, EPR, electrochemistry,
      electrophoresis, intrinsic viscosity, DSC, and dielectric spectroscopy.

PMID- 16289437
TI  - Practical conditions for photoaffinity labeling with 3-trifluoromethyl-3
      phenyldiazirine photophore.

PMID- 16289438
TI  - A solid-phase extraction/high-performance liquid chromatography-based (32)P
      postlabeling method for detection of cyclic 1,N(2)-propanodeoxyguanosine adducts
      derived from enals.
AB  - The cyclic 1,N(2)-propanodeoxyguanosine (PdG) adducts are Michael addition
      products from reactions of deoxyguanosine (dG) with enals, including acrolein
      (Acr), crotonaldehyde (Cro), pentenal (Pen), heptenal (Hep), and 4-hydroxy-2
      nonenal (HNE). Although this is a general reaction, only the PdG adducts derived
      from Acr, Cro, and HNE have been detected in vivo as endogenous DNA lesions. Our
      previous in vitro study demonstrated that PdG adducts of Acr, Cro, and Pen are
      predominantly derived from oxidation of omega-3 polyunsaturated fatty acids
      (PUFAs), whereas the long-chain Hep and HNE adducts are from omega-6 PUFAs. PdG
      adducts are important because they represent a new class of endogenous
      promutagenic DNA lesions with potential roles in carcinogenesis. Earlier, we
      developed a (32)P-postlabeling method for detecting PdG adducts from Acr and Cro
      and a modified method for the long-chain HNE adducts. Both methods require
      multiple high-performance liquid chromatography steps and, in some cases, time
      consuming thin-layer chromatography for purification. There is a lack of a
      single, versatile, and efficient method for simultaneous detection of all five
      enal-derived PdG adducts. In this paper, we report an improved (32)P-postlabeling
      method which permits detection of Acr, Cro, Pen, Hep, and HNE adducts in a single
      DNA sample. This method relies on solid-phase extraction for adduct enrichment
      before and after (32)P-labeling; all five PdG adducts were converted to the ring
      opened derivatives for confirmation of identities and quantification. The method
      was validated using the synthetic adducts and enal-modified DNA and was finally
      applied to rat liver DNA and rat liver DNA samples spiked with different amount
      of standards. The detection limit was determined to be as low as 0.5 fmol in 80
      microg DNA, corresponding to 9 adducts/10(9) dG.

PMID- 16289439
TI  - Oxidation of Good's buffers by hydrogen peroxide.
AB  - Good's zwitterionic buffers are widely used in biological and biochemical
      research in which hydrogen peroxide is a solution component. This study was
      undertaken to determine whether Good's buffers exhibit reactivity toward
      H(2)O(2). It is found that H(2)O(2) oxidizes both morpholine ring-containing
      buffers (e.g., Mops, Mes) and piperazine ring-containing zwitterionic buffers
      (e.g., Pipes, Hepes, and Epps) to produce their corresponding N-oxide forms. The
      percentage of oxidized buffer increases as the concentration of H(2)O(2)
      increases. However, the rate of oxidation is relatively slow. For example, no
      oxidized Mops was detected 2h after adding 0.1M H(2)O(2) to 0.1M Mops (pH 7.0),
      and only 5.7% was oxidized after 24h exposure to H(2)O(2). Thus, although all of
      these buffers can be oxidized by H(2)O(2), their slow reaction does not
      significantly perturb levels of H(2)O(2) in the time frame and at the
      concentrations of most biochemical studies. Therefore, the previously reported
      rapid loss of H(2)O(2) produced from the ferroxidase reaction of ferritin is
      unlikely due to reaction of H(2)O(2) with buffer, a conclusion supported by the
      fact that H(2)O(2) is also lost rapidly when the solution pH of the ferroxidase
      reaction is controlled by a pH stat apparatus in the absence of buffer.

PMID- 16289440
TI  - Analysis of recombinant monoclonal antibody isoforms by electrospray ionization
      mass spectrometry as a strategy for streamlining characterization of recombinant
      monoclonal antibody charge heterogeneity.
AB  - A therapeutic recombinant monoclonal antibody analyzed by cation-exchange
      chromatography exhibited a heterogeneous profile composed of approximately 10
      isoforms. The peaks were isolated and characterized by electrospray quadrupole
      time-of-flight mass spectrometry (ESI-q-TOF-MS), N-terminal Edman sequencing,
      peptide mapping, and other techniques. Acidic (lower pI) peaks were found to
      represent deamidated and sialyated species. Higher pI peaks were found to contain
      N- and C-terminal heavy-chain variants. Biological activities of the more
      abundant isoforms were found to be comparable. An approach streamlining the
      characterization of antibody charge heterogeneity is proposed.

PMID- 16289441
TI  - High-sensitive determination of coenzyme Q(10) in iodinate-beta-cyclodextrin
      medium by inclusion reaction and catalytic polarography.
AB  - A novel polarographic method for the determination of coenzyme Q(10) in beta
      cyclodextrin (beta-CD) and iodinate system is proposed. The stability of coenzyme
      Q(10) to light was improved by the formation of coenzyme Q(10)-beta-CD inclusion
      complex. In addition, the sensitivity for the determination of coenzyme Q(10) was
      enhanced by both the formation and the polarographic catalytic wave of the
      inclusion complex in the presence of iodinate. In 0.1 mol/L HAc-NaAc (pH 4.7)-5.0
      x 10(-5) mol/L beta-CD-1.2 x 10(-3) mol/L potassium iodinate-ethanol/water
      (60:40, v/v) medium, coenzyme Q(10)-beta-CD inclusion complex yielded a sensitive
      association/parallel catalytic wave. The second-order derivative peak current of
      the catalytic wave was proportional to coenzyme Q(10) concentration in the range
      of 6.0 x 10(-8)-2.5 x 10(-7) mol/L, and the detection limit was 1.0 x 10(-8)
      mol/L. The proposed method has high analytical sensitivity and is allowed to
      determine coenzyme Q(10) under light.

PMID- 16289442
TI  - Ligand binding to one-dimensional lattice-like macromolecules: analysis of the
      McGhee-von Hippel theory implemented in isothermal titration calorimetry.
AB  - The theory developed by McGhee and von Hippel for ligand binding to a one
      dimensional lattice-like macromolecule provides a closed analytical form in the
      Scatchard representation. The application of such theory has been complicated by
      two facts: (1) it has been practically reduced to binding techniques, such as
      equilibrium dialysis, in which the partition between bound and free
      concentrations of all reactant species are directly accessible and experimentally
      determined, but infrequently applied to other binding techniques, such as
      calorimetry or spectroscopy, in which the direct observable is a magnitude
      proportional to the advance of the binding reaction monitored along the titration
      experiment, and (2) Scatchard analysis, developed as a quantitative graphical
      method, is currently outdated and used only qualitatively because of its
      weaknesses, limitations, and deficiencies. However, a general exact method for
      applying such theory to titration techniques in a correct and precise manner,
      without any limitation, can be delineated. In this article, the theory of
      cooperative ligand binding to linear lattice-like macromolecules has been
      implemented in isothermal titration calorimetry for the first time. This
      technique provides a complete thermodynamic characterization of ligand binding,
      but it has been barely used properly for this type of system. The description,
      the analysis of the formalism, and practical guidelines are presented, with
      considerations for experimental design and data analysis.

PMID- 16289443
TI  - Isolation of high-quality DNA for genotyping from feces of rodents.

PMID- 16289444
TI  - A solid-phase immunoassay of protease-resistant prion protein with filtration
      blotting involving sodium dodecyl sulfate.
AB  - The precise diagnosis for bovine spongiform encephalopathy (BSE) is crucial for
      preventing new transmission to humans. Several testing procedures are reported
      for determining protease-resistant prion protein in various tissues as a major
      hallmark of prion diseases such as BSE, scrapie, and Creutzfeldt-Jakob disease.
      However, contamination of materials from tissues or degradation of the specimens
      sometimes disturbs the accuracy of the assay. Here, we have developed a novel
      method for solid-phase immunoassay of the disease-specific conformational
      isoform, PrP(Sc), using filtration blotting of protein in the presence of sodium
      dodecyl sulfate (SDS) followed by a filtration-based immunoassay with a single
      anti-prion protein antibody, together with the improved fractionation procedure
      involving high concentrations of surfactant/detergent. The SDS/heat treatment
      renders unfolded PrP(Sc) quantitative retention on a polyvinylidene difluoride
      filter and allows enhancement of the analyte signal with immunodetection; thus,
      all of the tested specimens are determined with 100% accuracy. In addition, the
      immunoassay is completed in approximately 1h, indicating its usefulness not only
      for the screening of BSE specimens but probably also for the postmortem BSE
      diagnosis of fallen stock as the antibody recognizes the core part of PrP(Sc).
      The solid-phase immunoassay method, including the filtration blotting with SDS,
      would be applicable to determining even more sensitively proteins other than
      PrP(Sc), especially those having rigid conformations.

PMID- 16289445
TI  - Determination of zinc in tissues of normal and dystrophic mice using
      electrothermal atomic absorption spectrometry and slurry sampling.
AB  - An electrothermal atomic absorption spectrometric procedure for zinc
      determination in animal tissues is first optimized and then used to measure the
      metal content of different tissues from normal and dystrophic mice. The procedure
      involves minimal manipulation of the sample to overcome the severe contamination
      problems normally associated with the measurement of low zinc levels. The samples
      (recommended amount 10 mg) are slurried in 2 ml of a 10-mM tetramethylammonium
      hydroxide solution containing 0.1 g/100 ml silicone antifoam. After mild heating
      at 60 degrees C for 10 min and homogenization for 1 min, the suspensions are
      submitted to a 10-fold dilution and then injected into the electrothermal
      atomizer. Calibration is carried out using aqueous standard solutions of zinc
      prepared in the same suspension media. The reliability of the whole procedure is
      verified using three certified reference materials.

PMID- 16289446
TI  - Identification of biogenic dimethyl selenodisulfide in the headspace gases above
      genetically modified Escherichia coli.
AB  - Escherichia coli JM109 cells were modified to express the genes encoded in a 3.8
      kb chromosomal DNA fragment from a metalloid-resistant thermophile, Geobacillus
      stearothermophilus V. Manual headspace extraction was used to collect the gases
      for gas chromatography with fluorine-induced sulfur chemiluminescence analysis
      while solid-phase microextraction was used for sample collection in gas
      chromatography/mass spectrometry (GC/MS) analysis. When grown in the presence of
      selenate or selenite, these bacteria produced both organo-sulfur and organo
      selenium in the headspace gases above the cultures. Organo-sulfur compounds
      detected were methanethiol, dimethyl sulfide, dimethyl disulfide, and dimethyl
      trisulfide. Organo-selenium compounds detected were dimethyl selenide and
      dimethyl diselenide. Two mixed sulfur-selenium compounds, dimethyl selenenyl
      sulfide and a chromatographically late-eluting compound, were detected. Dimethyl
      selenodisulfide, CH(3)SeSSCH(3), and dimethyl bis(thio)selenide, CH(3)SSeSCH(3),
      were synthesized and analyzed by GC/MS and fluorine-induced chemiluminescence to
      determine which corresponded to the late-eluting compound that was bacterially
      produced. CH(3)SeSSCH(3) was positively identified as the compound detected in
      bacterial headspace above Se-amended cultures. Using GC retention times, the
      boiling point of CH(3)SeSSCH(3) was estimated to be approximately 192 degrees C.
      This is the first report of CH(3)SeSSCH(3) produced by bacterial cultures.

PMID- 16289447
TI  - Multiplexed DNA sequencing-by-synthesis.
AB  - We report a new DNA sequencing-by-synthesis method in which the sequences of DNA
      templates, hybridized to a surface-immobilized array of DNA primers, are
      determined by sensing the number of nucleotides by which the primers in each
      array spot are extended in sequential DNA polymerase-catalyzed nucleotide
      incorporation reactions, each with a single fluorescein-labeled
      deoxyribonucleoside triphosphate (dNTP) species. The fluorescein label is
      destroyed after each readout by a photostimulated reaction with diphenyliodonium
      chloride. A DNA polymerase with enhanced ability to incorporate, and to extend
      beyond, modified nucleotides is used. Self-quenching of adjacent fluorescein
      labels, which impedes readout of homopolymeric runs, is avoided by diluting the
      labeled dNTP with unlabeled reagent. Misincorporation effects have been
      quantified and are small; however, low-level contamination of dNTPs with other
      nucleotides mimics misincorporation and can produce significant false-positive
      signals. These impurities are removed by polymerase-catalyzed incorporation into
      complementary "cleaning duplexes." Here, we demonstrate the accurate sequence
      readout for a small array of known DNA templates, the ability to quantify
      homopolymeric runs, and a short sequencing example of sections of the wild-type
      and mutant BRCA1 gene. For a 20,000-spot array, readout rates in excess of 6000
      bases per minute are projected.

PMID- 16289449
TI  - Determination of imperatorin in rat plasma by reversed-phase high-performance
      liquid chromatography after oral administration of Radix Angelicae dahuricae
      extract.
AB  - A simple high-performance liquid chromatographic (HPLC) method has been developed
      for the determination of imperatorin in rat plasma and applied to a
      pharmacokinetic study in rats after administration of Radix Angelicae dahuricae
      extract. After addition of fluocinonide as an internal standard (IS), plasma
      samples were extracted with diethyl ether. HPLC analysis of the extracts was
      performed on a Diamonsil C18 analytical column using methanol-water (70:30, v/v)
      as the mobile phase. The UV detector was set at 254 nm. The standard curve was
      linear over the range 0.04-4.0 microg/mL. The lower limit of quantification was
      0.04 microg/mL. The HPLC method developed could be easily applied to the
      determination and pharmacokinetic study of imperatorin in rat plasma after giving
      the animals Radix Angelicae dahuricae extract.

PMID- 16289448
TI  - Noelins modulate the timing of neuronal differentiation during development.
AB  - Noelins comprise a family of extracellular proteins with proposed roles in neural
      and neural crest development. Here, we show that a previously uncharacterized
      family member, Noelin-4, functions to maintain neural precursors in an
      undifferentiated state and biases ectoderm toward a neural fate. We show that
      Noelin-4 is induced by the neurogenic genes X-ngnr-1 and XNeuroD. Over-expression
      of Noelin-4 causes expansion of the neural plate at the expense of neural crest
      and epidermis. Although there is an apparent increase in the neural precursor
      pool, no increase was noted in differentiated neurons. Later, derivatives such as
      the neural tube and retina appear enlarged. We show biochemically that Noelin-4
      protein is glycosylated and secreted and that it interacts with Noelin-1, an
      isoform previously found to promote differentiation in neuralized animal caps.
      Accordingly, the neural precursor expansion activity of Noelin-4 is reversed by
      co-expression of Noelin-1. Our finding that Noelin isoforms can bind to and
      antagonize one another suggests that interacting Noelin isoforms may play a role
      in regulating timing of differentiation.

PMID- 16289450
TI  - MC4R oligomerizes independently of extracellular cysteine residues.
AB  - The melanocortin 4 receptor (MC4R) plays an essential role in weight regulation.
      Recently we could show that the MC4R is able to form receptor dimers. In the
      present study we investigated the role of extracellular cysteine residues and the
      structure of the third extracellular loop for receptor dimerization. None of the
      four extracellular cysteine residues nor the structure of the third extracellular
      loop play a role for MC4R-MC4R interaction as all investigated mutants display
      the same dimerization pattern as the wild-type receptor. Therefore for MC4R
      dimerization structures of the transmembrane-spanning helices are more likely to
      be involved.

PMID- 16289451
TI  - Neurobiology of relapse to heroin and cocaine seeking: an update and clinical
      implications.
AB  - The central problem in the treatment of cocaine and heroin addiction is high
      rates of relapse to drug use after periods of forced or self-imposed abstinence.
      Relapse can be modeled in laboratory animals a reinstatement procedure in which
      responding for drug is extinguished and then reinstated by acute exposure to the
      drug, drug cues, or stress. In this review, we first summarize data from recent
      (2003-2005) studies on the neural substrates involved in reinstatement of heroin
      and cocaine seeking. We also discuss the neural mechanisms underlying the
      progressive increase in cocaine seeking after withdrawal (incubation of cocaine
      craving). Finally, we provide an update on several novel candidate medications
      for relapse prevention suggested by recent preclinical studies, and we discuss
      the translation of findings from nonhuman laboratory studies to the clinical
      phenomenon of relapse.

PMID- 16289453
TI  - Antidepressant treatment and rodent aggressive behaviour.
AB  - This review examines two 'ethologically relevant' rodent models, the resident
      intruder and social hierarchy paradigms, that are sensitive to chronic
      antidepressant treatment (including repeated electroconvulsive shock). These
      models of rodent social and agonistic behaviour demonstrate that acute and
      chronic treatment with antidepressant drugs (regardless of their acute
      pharmacological activity) induce diametrically opposite changes in rodent
      aggressive behaviour. The common ability of chronic antidepressant treatment to
      increase rodent aggression (which in turn results in increased hierarchical
      status in closed social groups) most likely reflects the increased assertiveness
      and associated externalization of emotions (indicative of increased extrapunitive
      aggression) expressed during recovery from depressive illness. Finally, findings
      that relate observed behavioural changes to underlying neurochemical changes are
      briefly reviewed in terms of adaptive mechanisms in the rodent central nervous
      system induced by antidepressants, and also with respect to suicide ideation and
      panicogenic responses observed in some patients at the onset of treatment with
      selective serotonin reuptake inhibitors for affective disorders.

PMID- 16289452
TI  - Reducing effect of the positive allosteric modulators of the GABA(B) receptor,
      CGP7930 and GS39783, on alcohol intake in alcohol-preferring rats.
AB  - The gamma-aminobutyric acidB (GABA(B)) receptor full agonists, baclofen and
      CGP44532, have been found to suppress different aspects of alcohol drinking
      behavior, including acquisition and maintenance, in selectively bred Sardinian
      alcohol-preferring (sP) rats. The present study was designed to assess whether
      this capability extends to the recently synthesized, positive allosteric
      modulators of the GABA(B) receptor, 2,6-Di-tert-butyl-4-(3-hydroxy-2,2-dimethyl
      propyl)-phenol (CGP7930) and N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro
      pyrimidine-4,6-diamine (GS39783). In the "acquisition" experiments, CGP7930 (0,
      25, 50 and 100 mg/kg; i.g.) and GS39783 (0, 6.25, 12.5 and 25 mg/kg; i.g.) were
      administered for 5 consecutive days to alcohol-naive sP rats. In the
      "maintenance" experiments, (0, 50 and 100 mg/kg; i.g.) and GS39783 (0, 50 and 100
      mg/kg; i.g.) were administered for 5 consecutive days to alcohol-experienced sP
      rats. Alcohol intake was evaluated under the standard, homecage 2-bottle "alcohol
      (10%, v/v) vs water" regimen with unlimited access for 24 h/day. Both CGP7930 and
      GS39783 dose-dependently suppressed the acquisition of alcohol drinking behavior.
      In the "maintenance" experiments, CGP7930 and GS39783 reduced daily alcohol
      intake by 30-40% only at the highest dose when compared to vehicle-treated rats;
      this effect tended to vanish on continuing treatment. The results of the present
      study suggest that positive allosteric modulation of the GABA(B) receptor
      produced an effect on alcohol drinking behavior similar to that produced by
      GABA(B) receptor full agonists. These data also suggest that positive allosteric
      modulation of the GABA(B) receptor may constitute a potential strategy for
      developing new drugs for treating alcohol dependence.

PMID- 16289455
TI  - Case definition for community-associated methicillin-resistant Staphylococcus
      aureus.

PMID- 16289454
TI  - Effect of aminooxyacetic acid on extracellular level of D-serine in rat striatum:
      an in vivo microdialysis study.
AB  - To elucidate the effect of an inhibitor of pyridoxal phosphate-dependent enzymes,
      aminooxyacetic acid, on the activity of serine racemase in vivo, we have
      investigated the effect of aminooxyacetic acid on the extracellular concentration
      of D-serine in the rat striatum using an in vivo microdialysis technique. The
      intrastriatal perfusion of aminooxyacetic acid caused a significant decline in
      the extracellular concentration of D-serine. These data, together with the fact
      that serine racemase is a pyridoxal phosphate-dependent enzyme, suggest that the
      aminooxyacetic acid-induced reduction of the extracellular D-serine may be at
      least in part due to the drug's ability to inhibit serine racemase.

PMID- 16289456
TI  - Investigation of hospital-acquired infections due to Achromobacter xylosoxidans
      in a tertiary care hospital in India.

PMID- 16289457
TI  - Safe disposal of clinical waste: where is the science?

PMID- 16289458
TI  - Hydrogen peroxide vapour decontamination in an overcrowded tertiary care referral
      centre: some practical answers.

PMID- 16289459
TI  - Nosocomial outbreak of vanB2 vancomycin-resistant Enterococcus faecium in Sweden.

PMID- 16289460
TI  - Contamination of single-use Minims eye drops by multiple use in clinics.

PMID- 16289461
TI  - Hospital work as a major risk factor for Helicobacter pylori infection.

PMID- 16289462
TI  - No carriers of hepatitis C among operating room personnel in a university
      hospital setting in The Netherlands.

PMID- 16289463
TI  - Embryonic salivary gland dysmorphogenesis in Twisted gastrulation deficient mice.
AB  - OBJECTIVE: Mouse Twisted gastrulation gene (Twsg1) expression is found throughout
      embryonic development, including substantial levels in the first branchial arch
      that gives rise to the submandibular salivary gland (SMG). We addressed the
      proposition that normal Twsg1 expression is critical to normal SMG ontogenesis.
      DESIGN: Utilizing C57BL/6 embryos that were Twsg1-/- homozygotes, as well as wild
      type and heterozygote littermates, we investigated SMG development from
      gestational day 13 to newborn. RESULTS: Twsg1 protein is immunodetected in
      epithelia throughout SMG development. Twsg1-/- embryos display widely variable
      craniofacial phenotypes that range from normal to severe
      holoprosencephaly/agnathia with no mandibular arch or stomodeum. The SMG
      phenotypes are correlated with the external craniofacial phenotype, ranging from
      normal to agenesis/aplasia. CONCLUSIONS: It is evident that normal Twsg1
      expression is critical for normal mouse SMG ontogenesis. Twsg1 loss of function
      is ultimately epistatic to the epigenome under normal physiologic conditions, but
      not always so. The reduced penetrance and variable expressivity seen in the SMGs
      of Twsg1-/- embryos is a challenging enigma.

PMID- 16289465
TI  - Modulation of brain mitochondrial function by deprenyl.
AB  - The present study shows that deprenyl, a known inhibitor of monoamine oxidase B
      (MAO B), may generate changes in mitochondrial function. Brain submitochondrial
      membranes (SMP), synaptosomes and cytosolic fractions were incubated with
      different deprenyl concentrations and nitric oxide synthase (NOS) activity was
      measured. The effect of deprenyl on oxygen consumption, calcium-induced
      permeability transition and hydrogen peroxide (H(2)O(2)) production rates was
      studied in intact mitochondria. Respiratory complexes and monoamine oxidase
      activities were also measured in submitochondrial membranes. Incubation of brain
      submitochondrial membranes with deprenyl 10, 25 and 50 microM inhibited nitric
      oxide synthase activity in a concentration-dependent manner. The same effect was
      observed in cytosolic fractions and synaptosomes. Monoamine oxidase activity was
      inhibited at lower deprenyl concentrations (from 0.5 microM). Cytochrome oxidase
      (complex IV) activity was found 42% increased in the presence of 25 microM
      deprenyl in a condition of maximal nitric oxide synthase activity. Incubation of
      brain mitochondria with deprenyl 25 microM produced a 60% increase in oxygen
      uptake in state 3, but no significant changes were observed in state 4. Pre
      incubation of brain mitochondria with deprenyl 0.5 and 1 microM inhibited calcium
      induced mitochondrial permeability transition and decreased hydrogen peroxide
      production rates. Our results suggest that in vitro effects of deprenyl on
      mitochondrial function can occur through two different mechanisms, involving
      nitric oxide synthase inhibition and decreased hydrogen peroxide production.

PMID- 16289464
TI  - Endless versatility in the biotechnological applications of Kluyveromyces LAC
      genes.
AB  - Most microorganisms adapted to life in milk owe their ability to thrive in this
      habitat to the evolution of mechanisms for the use of the most abundant sugar
      present on it, lactose, as a carbon source. Because of their lactose-assimilating
      ability, Kluyveromyces yeasts have long been used in industrial processes
      involved in the elimination of this sugar. The identification of the genes
      conferring Kluyveromyces with a system for permeabilization and intracellular
      hydrolysis of lactose (LAC genes), along with the current possibilities for their
      transfer into alternative organisms through genetic engineering, has
      significantly broadened the industrial profitability of lactic yeasts. This
      review provides an updated overview of the general properties of Kluyveromyces
      LAC genes, and the multiple techniques involving their biotechnological
      utilization. Emphasis is also made on the potential that some of the latest
      technologies, such as the generation of transgenics, will have for a further
      benefit in the use of these and related genes.

PMID- 16289466
TI  - Plasmodium yoelii: axenic development of the parasite mosquito stages.
AB  - Study of the parasite mosquito stages of Plasmodium and its use in the production
      of sporozoite vaccines against malaria has been hampered by the technical
      difficulties of in vitro development. Here, we show the complete axenic
      development of the parasite mosquito stages of Plasmodium yoelii. While we
      demonstrate that matrigel is not required for parasite development, soluble
      factors produced and secreted by Drosophila melanogaster S2 cells appear to be
      crucial for the ookinete to oocyst transition. Parasites cultured axenically are
      both morphologically and biologically similar to mosquito-derived ookinetes,
      oocysts, and sporozoites. Axenically derived sporozoites were capable of
      producing an infection in mice as determined by RT-PCR; however, the parasitemia
      was significantly much less than that produced by mosquito-derived sporozoites.
      Our cell free system for development of the mosquito stages of P. yoelii provides
      a simplified approach to generate sporozoites that may be for biological assays
      and genetic manipulations.

PMID- 16289467
TI  - Toxoplasma gondii: Serological recognition of reinfection.
AB  - Using murine chronic toxoplasmosis as an experimental model, we examined the
      utility of immunoenzymatic methods in recognizing reinfection in chronically
      infected individuals. Primary infection with avirulent Toxoplasma gondii DX
      strain (genotype II) induced strong immunity protecting the mice from mortality
      after inoculation with LD(100) of virulent BK strain (genotype I) and triggered
      highly expressed antibody production, within one new isotype detected by
      comparative immunoblots. The parasites multiplying at the site of reinfection
      were of BK origin as found by RAPD-PCR. The results revealed that the immunoblot
      assay seems to be a useful and reliable method for the monitoring of specific
      antibody profile in chronically infected individuals. In our opinion ELISA
      combined with immunoblot could enable the recognition of reinfection cases in
      humans, but earlier our experimental data should be verified in clinical
      laboratory.

PMID- 16289468
TI  - Proton pumping by complex I (NADH:ubiquinone oxidoreductase) from Yarrowia
      lipolytica reconstituted into proteoliposomes.
AB  - The mechanism of energy converting NADH:ubiquinone oxidoreductase (complex I) is
      still unknown. A current controversy centers around the question whether electron
      transport of complex I is always linked to vectorial proton translocation or
      whether in some organisms the enzyme pumps sodium ions instead. To develop better
      experimental tools to elucidate its mechanism, we have reconstituted the affinity
      purified enzyme into proteoliposomes and monitored the generation of DeltapH and
      Deltapsi. We tested several detergents to solubilize the asolectin used for
      liposome formation. Tightly coupled proteoliposomes containing highly active
      complex I were obtained by detergent removal with BioBeads after total
      solubilization of the phospholipids with n-octyl-beta-D-glucopyranoside. We have
      used dyes to monitor the formation of the two components of the proton motive
      force,DeltapH and Deltapsi, across the liposomal membrane, and analyzed the
      effects of inhibitors, uncouplers and ionophores on this process. We show that
      electron transfer of complex I of the lower eukaryote Y. lipolytica is clearly
      linked to proton translocation. While this study was not specifically designed to
      demonstrate possible additional sodium translocating properties of complex I, we
      did not find indications for primary or secondary Na+ translocation by Y.
      lipolytica complex I.

PMID- 16289469
TI  - Endocrine and cellular characteristics of corpora lutea from cows with a delayed
      post-ovulatory progesterone rise.
AB  - The timing of the post-ovulatory progesterone rise is critical to the embryonic
      development and survival. The aim of this study was to determine the underlying
      causes of delayed post-ovulatory progesterone rises. Two groups of non-lactating
      dairy cows with early (n = 11) or late (n = 9) post-ovulatory progesterone rises
      were created by inducing luteolysis in the presence of either a large (> 10 mm)
      or small (< 10 mm) follicle, respectively. LH pulses were measured on days 4 (all
      cows) and 7 (n = 7, early; n = 5, late) (day 1= ovulation). The cows were
      slaughtered on day 5 (n = 4 each group) or 8 (n = 7, early; n = 5, late).
      Immunohistochemical analysis for endothelial cells (von Willebrand Factor, VWF),
      steroidogenic cells (3beta-HSD) and proliferation marker (Ki67) were performed.
      The basal progesterone production and LH responsiveness (0.001-100 ng/ml) of
      dispersed luteal cells was investigated. The luteal concentrations of FGF-2 and
      VEGF were measured by ELISA and RIA, respectively. There were no differences in
      LH pulse characteristics, area of VWF staining, proliferation index,
      steroidogenic cell characteristics, basal or LH-stimulated progesterone
      production by luteal cells between cows with an early or late progesterone rise
      (P > 0.10). However, the area of VWF staining increased from days 5 to 8, while
      the proliferation index decreased (P < 0.05). Furthermore, the luteal cells were
      more responsive to LH on day 8 (P < 0.01). Luteal concentrations of FGF-2 were
      higher on day 5 (P = 0.05), while VEGF was greater on day 8 (P < 0.01). In
      conclusion, we have clearly shown that LH support, degree of vascularization or
      luteal cell steroidogenic capacity were not the major factors responsible for
      inadequate secretion of progesterone by the developing bovine CL.

PMID- 16289470
TI  - Effect of eel calcitonin glycosylation on incorporation and channel formation in
      planar phospholipid membranes.
AB  - Previous studies have shown that different calcitonins interact with planar lipid
      membranes to form ion channels. In this study, glycosylation of eel calcitonin
      (eCt) at different positions (Ct3-GlcNAc, Ct14-GlcNAc, Ct20-GlcNAc, Ct26-GlcNAc)
      is shown to preserve molecular structure and slightly change the energy of
      incorporation and channel formation in planar lipid bilayers made up of palmitoyl
      oleoyl-phosphatidylcholine:dioleoyl phosphatidyl-glycerol (85:15, w:w). The
      voltage needed to form channels decreased as the attached carbohydrate moved
      toward the C-terminal (eCt = Ct3-GlcNAc > Ct14-GlcNAc = Ct20-GlcNAc > Ct26
      GlcNAc). Interestingly, all the Cts tested maintain the characteristic voltage
      conductance dependence found for other Cts, the only channel properties modified
      concern ion selectivity, that shift toward anion selectivity (eCt = 0.97, Ct3
      GlcNAc = 0.49, Ct14-GlcNAc = 0.41, Ct20-GlcNAc = 0.36, Ct26-GlcNAc = 0.47). These
      aspects would be useful in managing peptide properties for biotechnological and
      therapeutic applications considering the physiological nature of this peptide.

PMID- 16289471
TI  - Isolation and characterization of a novel platelet aggregation inhibitory peptide
      from the medicinal mushroom, Inonotus obliquus.
AB  - This study describes the extraction and characterization of a platelet
      aggregation inhibitory peptide from Inonotus obliquus. Ethanol extract from I.
      obliquus ASI 74006 mycelia showed the highest platelet aggregation inhibitory
      activity (81.2%). The maximum platelet aggregation inhibitory activity was found
      when the mycelia of I. obliquus ASI 74006 was extracted with ethanol at 80
      degrees C for 12 h. The platelet aggregation inhibitor was purified by systematic
      solvent fractionation, ultrafiltration, Sephadex G-10 column chromatography, and
      reverse-phase HPLC. The purified platelet aggregation inhibitor is a novel
      tripeptide with a molecular mass of 365 Da, having a sequence of Trp-Gly-Cys. The
      purified platelet aggregation inhibitor also showed high platelet aggregation
      inhibitory activity in Institute of Cancer Research (ICR) mice.

PMID- 16289472
TI  - Stress and pain responses in rats lacking CCK1 receptors.
AB  - CCK involvement in stress- and pain-responsiveness was examined by studying the
      behavior of infant (11-12-days-old) and adult OLETF rats that do not express CCK1
      receptors. Infant odor- and texture-preferences were also assessed. We
      hypothesized that OLETF rats will show behavioral patterns similar to those
      previously observed after CCK1 antagonist administration. Rate of separation
      induced ultrasonic vocalization was significantly greater in OLETF compared to
      controls, in two separate studies. Infant pups of the two strains did not differ
      in odor- and texture-preference tests. OLETF rats showed consistently longer hot
      plate paw-lift (as infants, in two separate studies) and paw-lick (as adults)
      latencies. SUMMARY: OLETF pups vocalized in isolation more than controls and
      showed relative hypoalgesic responses, evident also in adulthood, in concordance
      with the pharmacological literature.

PMID- 16289473
TI  - A role for syndecan-3 in the melanocortin regulation of energy balance.
AB  - Since the discovery that central melanocortin peptides play an important role in
      the control of body weight, an impressive amount of research has focused on
      understanding this complex neuroendocrine system. However, this research has also
      uncovered new complexities. One of these complexities is the recently discovered
      putative melanocortin "co-receptor," syndecan-3. In this review, we present an
      overview of the biology and potential functions of syndecan-3 and describe a
      novel hypothesis for its regulation of energy balance.

PMID- 16289474
TI  - Citropin 1.1-treated central venous catheters improve the efficacy of hydrophobic
      antibiotics in the treatment of experimental staphylococcal catheter-related
      infection.
AB  - An in vitro antibiotic susceptibility assay for Staphylococcus aureus biofilms
      developed on 96-well polystyrene tissue culture plates was performed to elucidate
      the activity of citropin 1.1, rifampin and minocycline. Efficacy studies were
      performed in a rat model of staphylococcal CVC infection. Silastic catheters were
      implanted into the superior cava. Twenty-four hours after implantation the
      catheters were filled with citropin 1.1 (10 microg/mL). Thirty minutes later the
      rats were challenged via the CVC with 1.0 x 10(6) CFU of S. aureus strain Smith
      diffuse. Administration of antibiotics into the CVC (the antibiotic lock
      technique) began 24 h later. The study included: one control group (no CVC
      infection), one contaminated group that did not receive any antibiotic
      prophylaxis, one contaminated group that received citropin 1.1-treated CVC, two
      contaminated groups that received citropin 1.1-treated CVC plus rifampin and
      minocycline at concentrations equal to MBCs for adherent cells and 1024 microg/mL
      in a volume of 0.1 mL that filled the CVC and two contaminated groups that
      received rifampin or minocycline at the same concentrations. All catheters were
      explanted 7 days after implantation. Main outcome measures were: minimal
      inhibitory concentration (MIC), minimal bactericidal concentration (MBC), synergy
      studies, quantitative culture of the biofilm formed on the catheters and
      surrounding venous tissues, and quantitative peripheral blood cultures. MICs of
      conventional antibiotics against the bacteria in a biofilm were at least four
      fold higher than against the freely growing planktonic cells. In contrast, when
      antibiotics were used on citropin 1.1 pre-treated cells they showed comparable
      activity against both biofilm and planktonic organisms. The in vivo studies show
      that when CVCs were pre-treated with citropin 1.1 or with a high dose of
      antibiotics, biofilm bacterial load was reduced from 10(7) to 10(3) CFU/mL and
      bacteremia reduced from 10(3) to 10(1) CFU/mL. When CVCs were treated both with
      citropin 1.1 and antibiotics, biofilm bacterial load was further reduced to 10(1)
      CFU/mL and bacteremia was not detected, suggesting 100% elimination of bacteremia
      and a log 6 reduction in biofilm load. Citropin 1.1 significantly reduces
      bacterial load and enhances the effect of hydrophobic antibiotics in the
      treatment of CVC-associated S. aureus infections.

PMID- 16289475
TI  - Changes in the properties of the modulatory cerebral giant cells contribute to
      aging in the feeding system of Lymnaea.
AB  - This study examined whether electrophysiological changes in the endogenous
      properties and connectivity of the modulatory serotonergic cerebral giant cells
      (CGCs) contributed to the age-related changes in feeding behavior of the pond
      snail, Lymnaea. With increasing age there was a decrease in spontaneous CGC
      firing rates and decreased excitability of the CGCs to both chemosensory
      stimulation (0.05M sucrose applied to the lips) and direct intracellular current
      injection. These changes could be accounted for by a decrease in the input
      resistance of the neuron and an increase in the amplitude and the duration of the
      after-hyperpolarization. Decreases were also seen in the % of CGC pairs that were
      electrically coupled causing asynchronous firing. Together these changes would
      tend to reduce the ability of the CGCs to gate and control the frequency of the
      feeding behavior. Part of the ability of the CGCs to gate and frequency control
      the feeding network is to provide a background level of excitation to the feeding
      motor neurons. Recordings from B1 and B4 motor neurons showed an age-related
      hyperpolarization of the resting membrane potential consistent with a deficit in
      CGC function. Increases were seen in the strength of the evoked CGC-->B1
      connection, however, this increase failed to compensate for the deficits in CGC
      excitability. In summary, age-related changes in the properties of the CGCs were
      consistent with them contributing to the age-related changes in feeding behavior
      seen in Lymnaea.

PMID- 16289476
TI  - Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive
      impairment.
AB  - One of the major neuropathological findings in the brains of individuals with
      Alzheimer's disease (AD) is a loss of synaptic contacts in both the neocortex and
      hippocampus. Here we report, for the first time, an estimate of the total number
      of synapses in the outer molecular layer (OML) of the human dentate gyrus, in
      individuals with early Alzheimer's disease (eAD), mild cognitive impairment
      (MCI), or no cognitive impairment (NCI). An unbiased stereologic sampling scheme
      coupled with transmission electron microscopy to directly visualize synaptic
      contacts, was used to estimate the total number of synapses in short postmortem
      autopsy tissue. Individuals with eAD had significantly fewer synapses than the
      other two diagnostic groups. Seventy-five percent of the individuals with MCI had
      synaptic values that were lower than the NCI group mean. The number of synapses
      showed a significant correlation with the subject's Mini-Mental State score and
      with cognitive tests involving delayed recall. Synaptic loss showed no
      relationship to Braak stage or to apoE genotype. The volume of the OML was
      significantly reduced in eAD compared to the other two diagnositic groups that
      were not different from each other. These data suggest that a loss of afferents
      from the entorhinal cortex underlie the synapse loss seen in eAD. This study
      supports the concept that synapse loss is an early event in the disease process
      and suggests that MCI may be a transition stage between eAD and NCI with synaptic
      loss a structural correlate involved in cognitive decline.

PMID- 16289477
TI  - The cell cycle regulator p27Kip1 interacts with MCM7, a DNA replication licensing
      factor, to inhibit initiation of DNA replication.
AB  - The G1/S phase restriction point is a critical checkpoint that interfaces between
      the cell cycle regulatory machinery and DNA replicator proteins. Here, we report
      a novel function for the cyclin-dependent kinase inhibitor p27Kip1 in inhibiting
      DNA replication through its interaction with MCM7, a DNA replication protein that
      is essential for initiation of DNA replication and maintenance of genomic
      integrity. We find that p27Kip1 binds the conserved minichromosome maintenance
      (MCM) domain of MCM7. The proteins interact endogenously in vivo in a growth
      factor-dependent manner, such that the carboxyl terminal domain of p27Kip1
      inhibits DNA replication independent of its function as a cyclin-dependent kinase
      inhibitor. This novel function of p27Kip1 may prevent inappropriate initiation of
      DNA replication prior to S phase.

PMID- 16289478
TI  - Impaired ATP-binding cassette transporter A1-mediated sterol efflux from oxidized
      LDL-loaded macrophages.
AB  - We investigated the interaction of oxidized low density lipoprotein (OxLDL) with
      the ATP-binding cassette A1 (ABCA1) pathway in J774 macrophages. Cellular efflux
      to apolipoprotein AI (apo-AI) of OxLDL-derived cholesterol was lower than efflux
      of cholesterol derived from acetylated low density lipoprotein (AcLDL). ABCA1
      upregulation by 8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate (cpt
      cAMP) or 22 (R)-hydroxycholesterol (22-OH) and 9-cis retinoic acid (9cRA)
      increased the efflux to apo-AI of cellular sterols derived from AcLDL, but not of
      those from OxLDL. AcLDL, but not OxLDL, induced ABCA1 protein content and
      activity in J774. However, OxLDL did not influence J774 ABCA1 upregulation by cpt
      cAMP or 22-OH/9cRA. We conclude that sterols released to cells by OxLDL are
      available neither as substrate nor as modulator of ABCA1.

PMID- 16289479
TI  - Structural changes in a binary mixed phospholipid bilayer of DOPG and DOPS upon
      saposin C interaction at acidic pH utilizing 31P and 2H solid-state NMR
      spectroscopy.
AB  - Saposin C (Sap C) is known to stimulate the catalytic activity of the lysosomal
      enzyme glucosylceramidase (GCase) that facilitates the hydrolysis of
      glucosylceramide to ceramide and glucose. Both Sap C and acidic phospholipids are
      required for full activity of GCase. In order to better understand this
      interaction, mixed bilayer samples prepared from dioleoylphosphatidylglycerol
      (DOPG) and dioleoylphosphatidylserine (DOPS) (5:3 ratio) and Sap C were
      investigated using (2)H and (31)P solid-state NMR spectroscopy at temperatures
      ranging from 25 to 50 degrees C at pH 4.7. The Sap C concentrations used to carry
      out these experiments were 0 mol%, 1 mol% and 3 mol% with respect to the
      phospholipids. The molecular order parameters (S(CD)) were calculated from the
      dePaked (2)H solid-state NMR spectra of Distearoyl-d70-phosphatidylglycerol (DSPG
      d70) incorporated with DOPG and DOPS binary mixed bilayers. The S(CD) profiles
      indicate that the addition of Sap C to the negatively charged phospholipids is
      concentration dependent. S(CD) profiles of 1 mol% of the Sap C protein show only
      a very slight decrease in the acyl chain order. However, the S(CD) profiles of
      the 3 mol% of Sap C protein indicate that the interaction is predominantly
      increasing the disorder in the first half of the acyl chain near the head group
      (C1-C8) indicating that the amino and the carboxyl termini of Sap C are not
      inserting deep into the DOPG and DOPS mixed bilayers. The (31)P solid-state NMR
      spectra show that the chemical shift anisotropy (CSA) for both phospholipids
      decrease and the spectral broadening increases upon addition of Sap C to the
      mixed bilayers. The data indicate that Sap C interacts similarly with the head
      groups of both acidic phospholipids and that Sap C has no preference to DOPS over
      DOPG. Moreover, our solid-state NMR spectroscopic data agree with the structural
      model previously proposed in the literature [X. Qi, G.A. Grabowski, Differential
      membrane interactions of saposins A and C. Implication for the functional
      specificity, J. Biol. Chem. 276 (2001) 27010-27017] [1].

PMID- 16289480
TI  - Structural-activity relationship study on C-4 carbon atom of the CB1 antagonist
      SR141716: synthesis and pharmacological evaluation of 1,2,4-triazole-3
      carboxamides.
AB  - A series of 1,2,4-triazole-3-carboxamides has been prepared from alkyl-1,2,4
      triazole-3-carboxylates under mild conditions. The ability of these triazoles to
      displace [3H]-CP55940 from CB1 cannabinoid receptor was measured. However, they
      showed only poor to moderate binding affinities, indicating that substitution of
      the C-4 pyrazole atom of the CB1 reference compound SR141716 by a nitrogen atom
      results in loss of affinity. Further investigations for functionality indicated
      that the compound 6a exhibited significant cannabinoid antagonistic properties in
      the mouse vas deferens functional assay. This leads us to the conclusion that 6a
      binds at a different CB1 binding site or at a new cannabinoid receptor subtype.

PMID- 16289481
TI  - An alternative technique for totally implantable central venous access devices. A
      retrospective study of 1311 cases.
AB  - AIM: The aim of the present study was to report our experience of totally
      implantable central venous access devices (TICVAD) implantation using two
      techniques and attempt to define the better technique. MATERIALS AND METHODS:
      From January 1998 to September 2003, 1131 patients were reviewed and divided into
      two groups with implantation by cephalic vein cut-down (group A) done by general
      surgeons and subclavian vein puncture with the Seldinger technique (group B) done
      by vascular surgeons. The operative time, early and late complications of these
      two groups were compared. Data were analysed by Student's t-test. RESULTS: The
      average of operative time was 43 min in group A (35-70 min) and 40 min in group B
      (35-60 min) (P>0.05). No post-operative pneumothorax, hemothorax and
      fragmentation occurred in group A; the incidence of peri-operative complication
      was higher in group B. The overall and early complications of group A were
      significantly lower than that of group B (P<0.0001). CONCLUSION: This
      retrospective study showed that the cephalic vein cut-down approach for TICVAD
      placement avoided the risks of pneumothorax, hemothorax and catheter
      fragmentation.

PMID- 16289482
TI  - Synthesis and evaluation of 7-amino-2-(2(3)-furyl)-5-phenylethylamino-oxazolo[5,4
      d]pyrimidines as potential A2A adenosine receptor antagonists for positron
      emission tomography (PET).
AB  - The brain A2A adenosine receptor (A2AAR) participates with the dopamine D2
      receptor in the control of movement and also might influence behavior. Because
      PET is an important tool for studying the roles of receptors in disease, a ligand
      for imaging the brain A2AAR is desirable. This report describes the synthesis and
      A2AAR antagonist activities of a panel of phenyl-substituted 7-amino-2-(2-furyl)
      5-phenylethylamino-oxazolo[5,4-d]pyrimidines, 11aa-af, and their 3-furyl
      congeners, 11ba-bd. In competitive binding studies all compounds displaced
      [3H]CGS21680 from the A2AAR with Ki values of 14-33 nM with selectivity for the
      A2AAR over the A1AR of 5- to 94-fold. Autoradiography of brain sections showed a
      high level of unspecific binding that obscured specific binding. Thus, these
      compounds are not promising PET ligands.

PMID- 16289483
TI  - Evaluation of the immortalized human brain capillary endothelial cell line BB19
      as a human cell culture model for the blood-brain barrier.
AB  - In vitro models of the blood-brain barrier (BBB) play a major role in the study
      of BBB permeability of drug candidates. However, most established in vitro models
      use cells of non-human origin, which is not optimal for the prediction of brain
      permeability in humans. The aim of this study was to assess the human brain
      capillary endothelial cell line BB19 for its usefulness as an in vitro model of
      the human BBB. Restrictive tight junctions are a prerequisite for drug transport
      studies. Sucrose permeability of BB19 cells on different filters was compared to
      porcine brain capillary endothelial cells (BCEC). Tightness of BB19 cell
      monolayers still needs further optimization. Hardly any discrimination between
      Sucrose and Propranolol (P(app) = 1.30 x 10(-5) vs. 2.18 x 10(-5) cm/s) was seen.
      Cells showed an improvement towards a more primary BCEC morphology with C6
      conditioned medium, dexamethasone, and 1,25-dihydroxyvitamin D3. The presence of
      P-glycoprotein (P-gp), MRP4 and BCRP, ABC-transporters located in the BBB, has
      been shown on mRNA level, by immunostaining, and western blot. MRP1, MRP2, MRP5,
      OAT3, and OAT4 were also detected by RT-PCR. Functional properties of the BBB
      were shown with uptake of propranolol, morphine, and sucrose. Uptake studies with
      daunomycin and the P-gp inhibitor verapamil showed functional activity of P-gp.
      We conclude that BB19 cells might be feasible as a human in vitro model of the
      BBB for drug uptake studies. However, for the assessment of transport studies,
      further improvements of this model are necessary.

PMID- 16289484
TI  - Hypothermia and ERK activation after cardiac arrest.
AB  - Mild hypothermia improves survival and neurological outcome after cardiac arrest,
      as well as increasing activation of the extracellular-signal-regulated kinase
      (ERK) in hippocampus. ERK signaling is involved in neuronal growth and survival.
      We tested the hypothesis that the beneficial effects of hypothermia required ERK
      activation. ERK activation was measured by immunoblotting with phosphorylation
      specific antibodies. Rats (n = 8 per group) underwent 8 min of asphyxial cardiac
      arrest and were resuscitated with chest compressions, ventilation, epinephrine
      and bicarbonate. At 30 min after resuscitation, vehicle (50% saline:50% DMSO) or
      the ERK kinase inhibitor U0126 (100 microg) was infused into the lateral
      ventricle. Cranial temperature was kept at either 33 degrees C (hypothermia) or
      37 degrees C (normothermia) between 1 and 24 h. Neurological function was
      assessed daily for 14 days. Surviving neurons were counted in the hippocampus. A
      dose of 100 mug U0126 inhibited ERK bilaterally for 12 to 24 h and decreased
      phosphorylation of the ERK substrates ATF-2 and CREB. As in previous studies,
      hypothermia improved survival, neurological and histological outcome after
      cardiac arrest. However, survival, neurological score and histology did not
      differ between U0126 and vehicle-treated rats after cardiac arrest. Therefore, a
      dose of U0126 sufficient to inhibit biochemical markers of ERK signaling in
      hippocampus does not alter the beneficial effects of hypothermia induced after
      resuscitation in rats and did not affect recovery of normothermia-treated rats.
      These results suggest that hypothermia-induced improvement in outcomes does not
      require ERK activation.

PMID- 16289485
TI  - Neural stem cell grafts reduce the extent of neuronal damage in a mouse model of
      global ischaemia.
AB  - The therapeutic potential of neural stem cell transplantation has been well
      demonstrated in many models of focal brain damage. However, few studies have
      sought to determine whether neural stem cells are therapeutic in models of
      diffuse brain injury, such as observed in Alzheimer's disease and global
      ischaemia. The present study investigated the effects of transplanted MHP36
      neural stem cells on the extent of ischaemic damage in a mouse model of global
      ischaemia and the effects of the immunosuppressive agent cyclosporin A (CsA).
      C57Bl/6J mice received an intrastriatal graft of MHP36 neural stem cells 3 days
      after selective neuronal damage had been induced by global ischaemia. The
      experimental group was subdivided into CsA or saline controls. We discovered that
      grafts of MHP36 neural stem cells were able to differentiate into neurons and
      reduce the extent of ischaemic neuronal damage. This reduction was particularly
      apparent at 4 week post-transplantation and is independent of CsA
      immunosuppression. MHP36 cells survived robustly in host ischaemic brain and
      migrated away from the injection tract towards the caudate nucleus and corpus
      callosum. Although MHP36 grafts were associated with an acute inflammatory
      response from reactive astrocytes and microglia at 1 week post-transplantation,
      this decreased markedly by 4 weeks post-transplantation even in the absence of
      CsA immunosuppression. This is the first study showing a therapeutic benefit of
      neural stem cells in a highly diffuse brain injury, further highlighting the
      possibilities of stem cell transplantation for all types of neurodegenerative
      disease.

PMID- 16289486
TI  - Ontogenesis of photoperiodic entrainment of the molecular core clockwork in the
      rat suprachiasmatic nucleus.
AB  - The molecular mechanism underlying a generation of circadian rhythmicity within
      the suprachiasmatic nucleus (SCN) is based on interactive negative and positive
      feedback loops that drive the rhythmic transcription of clock genes and
      translation of their protein products. In adults, the molecular mechanism is
      affected by seasonal changes in day length, i.e., photoperiod. The photoperiod
      modulates phase, waveform, and amplitude of the rhythmic clock genes expression
      as well as the phase relationship between their profiles. To ascertain when and
      how the photoperiod affects the circadian core clock mechanism during
      ontogenesis, the rhythmic expression of clock genes, namely of Per1, Per2, Cry1
      and Bmal1 was determined in 3-, 10- and 20-day-old rat pups maintained under
      either a long photoperiod with 16 h of light and 8 h of darkness per day (LD
      16:8) or under a short, LD 8:16 photoperiod. The daily profiles in the level of
      clock genes mRNA were studied in constant darkness. The photoperiod affected the
      profile of Per1 and Per2 mRNA in 20- and 10- but not yet in 3-day-old pups.
      Expression of Cry1 was affected only in 20-day-old pups, whereas expression of
      Bmal1 was not yet affected even in 20-day-old rats. The results demonstrate no
      effect of the photoperiod on 3-day-old pups, only partial entrainment of the
      molecular core clockwork in 10-day-old pups and a more mature, though not yet
      fully complete, entrainment in 20-day-old pups as compared with adult animals.
      The developmental interval when the photoperiod begins to entrain the core clock
      mechanism completely might thus occur around the time of weaning.

PMID- 16289487
TI  - Antinociception following application of DAMGO to the basolateral amygdala
      results from a direct interaction of DAMGO with Mu opioid receptors in the
      amygdala.
AB  - Previous studies from our laboratory have shown that application of the mu opioid
      agonist DAMGO into the basolateral region of the amygdala (BLA) suppresses the
      radiant heat tail flick (TF) reflex in anesthetized rats. This antinociceptive
      effect can be blocked by lesions of brainstem regions such as the periaqueductal
      gray (PAG) or the rostral ventromedial medulla (RVM) or by functional
      inactivation of neurons in these regions, suggesting the activation of brainstem
      descending antinociceptive systems from the amygdala. However, little is known
      about the direct interaction of DAMGO with mu receptors in the amygdala. In the
      present series of experiments, the BLA was pretreated with opioid receptor
      antagonists and a G protein inhibitor prior to TF testing with application of
      DAMGO into the same site. Rats pretreated with the non-selective opioid
      antagonist naltrexone (1.25-3.75 microg/0.25 microl per side) or the G protein
      inhibitor pertussis toxin (0.25 microg) failed to show inhibition of TF reflexes
      following infusion of DAMGO (0.168-0.50 microg), indicating that DAMGO works
      through G-protein-coupled opioid receptors in the BLA. Furthermore, pretreatment
      with the mu antagonist beta-FNA (1.00-2.00 microg) attenuated antinociception
      induced by DAMGO injection, suggesting DAMGO's action on mu receptors in the BLA.
      Accordingly, we confirm a direct interaction of DAMGO with G-protein-coupled mu
      receptors in the BLA contributing to induction of opioid antinociception in the
      amygdala.

PMID- 16289488
TI  - Posttranslational processing of proopiomelanocortin family molecules in sea
      lamprey based on mass spectrometric and chemical analyses.
AB  - In gnathostomes, adrenocorticotropic hormone (ACTH), melanophore-stimulating
      hormones (MSHs), and beta-endorphin (beta-END) are derived from a common
      precursor, proopiomelanocortin. In sea lamprey, ACTH and two forms of MSHs are
      contained in independent precursors, proopiocortin (POC), and proopiomelanotropin
      (POM), respectively, together with a distinct beta-END. Here, we characterized
      products from POC and POM. An analysis of previously purified ACTH by mass
      spectrometry (MS) detected four peptides with a molecular weight of 6469.4,
      6549.6, 6556.6, or 6636.1. The sequence analysis of an ACTH preparation following
      enzymatic and chemical cleavage revealed the presence of ACTH(1-59) and ACTH(1
      60) corresponding to a molecular weight of 6469.4 and 6556.6, respectively, and
      of ACTH(1-59) and ACTH(1-60) modified at Ser(35) by a group having a mass of 80,
      giving the molecular weight 6549.6 and 6636.1, respectively. The modification
      could be due to phosphorylation based on the increase in molecular weight of 80.
      Analyses of frozen pituitary slices with MALDI-TOF MS detected several mass
      numbers corresponding to POC-derived peptides such as ACTH(1-60), modified ACTH(1
      60), and (POC)beta-END, and those corresponding to POM-derived peptides such as
      MSH-A, MSH-B, and the C-terminal fragment of (POM)beta-END lacking a Met
      enkephalin segment. The present results together with previous characterizations
      show that in sea lamprey pituitary the major products derived from POC in the PD
      by posttranslational processing are ACTH and beta-END as in gnathostomes. The
      posttranslational processing of POM in the PI is similar to that in gnathostomes
      in the sense of the occurrence of MSH, however, it differs in that beta-END is
      further cleaved, thus generating Met-enkephalin.

PMID- 16289489
TI  - A review of evaluative studies of computer-based learning in nursing education.
      2001.

PMID- 16289490
TI  - Nurse teachers in higher education--without clinical competence, do they have a
      future? 1994.

PMID- 16289491
TI  - Quality assurance in nurse education--the social context of learning. 1989.

PMID- 16289492
TI  - Nurses' perceptions of their interpersonal skills: a descriptive study using six
      category intervention analysis. 1988.

PMID- 16289493
TI  - Human primary renal cells as a model for toxicity assessment of chemo-therapeutic
      drugs.
AB  - Chemo-therapeutic drugs act on cancerous and normal cells non-selectively and
      often cause organ impairments during treatment. Improving safety or reducing
      toxicity becomes an important challenge for developing better anticancer drugs.
      In the present study, effects of selected anticancer drugs (camptothecin,
      doxorubicin, colchicine, paclitaxel, cisplatin, and carboplatin) on cell
      viability and proliferation was investigated. The anti-proliferative activity of
      each drug on cancer cells (human hepatoma HepG2) and human primary renal proximal
      tubule cells (hRPTECs and LLC-PK1) was determined with the [(3)H]thymidine
      incorporation assay. Results indicated all six drugs blocked cell proliferation
      in cancer and normal cells. When the anti-proliferation potency was ranked in
      hRPTECs based on EC50 values, camptothecin is the most potent, followed by
      doxorubicin, paclitaxel, colchicine, cisplatin and carboplatin. Cytotoxicity of
      drugs to hRPTECs was assessed with the ATP bioluminescence assay. Doxorubicin and
      cisplatin were known to induce nephrotoxicity in vivo and they were indeed
      cytotoxic to hRPTECs in our study with EC50 values at 11.2 and 39.6 microM. All
      other drugs are not cytotoxic in the concentrations tested. These drugs typically
      displayed separation of EC50s between potency (anti-proliferation) and
      cytotoxicity. The dose separation provides a concentration range for each drug to
      act on cell proliferation without induction of significant cytotoxicity. Our
      results suggest that hRPTEC system can serve as an in vitro model for assessing
      potential nephrotoxicity of chemo-therapeutic drugs.

PMID- 16289494
TI  - [Coeliac disease and autoimmunity: about an association with autoimmune
      haemolytic anaemia].

PMID- 16289495
TI  - 'Click chemistry' on polysaccharides: a convenient, general, and monitorable
      approach to develop (1-->3)-beta-D-glucans with various functional appendages.
AB  - (1-->3)-beta-D-Glucans having various functional appendages (lactoside,
      ferrocene, pyrene, and porphyrin) can be prepared in an convenient, quantitative,
      and regioselective manner through regioselective bromination-azidation of curdlan
      to afford 6-azido-6-deoxycurdlan followed by chemoselective [3+2]-cycloadditions
      with various functional modules bearing a terminal alkyne group. The ability to
      monitor reaction conversions is an additional advantage of this synthetic
      approach over the conventional direct modifications on polysaccharides; the
      reaction can be readily monitored based on the intensity of azido peaks in the in
      situ attenuated total reflection infrared spectra.

PMID- 16289496
TI  - The effects of paradoxical sleep deprivation on estrous cycles of the female
      rats.
AB  - The present purpose was to examine how sleep deprivation affects the estrous
      cycle of the female rat. Paradoxical sleep-deprived (PSD) adult female Wistar
      rats were compared to home-cage control (CTRL) on their estrous cyclicity. Forty
      four PSD and forty-four CTRL female rats were distributed into 4 subgroups of 11
      animals each according to the phase of estrous cycle and were subjected to sleep
      deprivation for 96 h by the multiple platform technique. After PSD period,
      vaginal estrous cycles were taken for an additional 9 days. Animals that were
      submitted to PSD in diestrus phase (PSD-diestrus) had their estrous cycles
      disrupted during the recovery period by showing a constant diestrus during the
      first week. As for hormone alterations, progesterone concentrations were
      statistically higher in PSD-diestrus compared to respective phase control and to
      PSD-proestrus and PSD-estrus rats while CTRL-metestrus had higher levels than
      CTRL-proestrus and estrus groups. Testosterone was significantly decreased in PSD
      estrus in relation to PSD-proestrus and PSD-diestrus groups and was lower in CTRL
      diestrus rats than in home-cage rats in proestrus. In addition, PSD-diestrus
      phase exhibited higher concentrations of corticosterone and lower estrogen than
      the respective control rats. These data indicate that PSD may modulate the
      ovarian hormone release through alterations in hormonal-neurochemical mechanisms.

PMID- 16289497
TI  - Nuclear parcellation of certain immunohistochemically identifiable neuronal
      systems in the midbrain and pons of the Highveld molerat (Cryptomys hottentotus).
AB  - The present paper details our findings following immunohistochemical examination
      of the midbrain and pons of the Highveld molerat (Cryptomys hottentotus) using
      antibodies for vesicular acetylcholine transporter (cholinergic neurons),
      tyrosine hydroxylase (dopaminergic and noradrenergic neurons), and serotonin
      (serotonergic neurons). The aim was to see if, in this microphthalmic rodent that
      lacks a distinct circadian rhythm, the nuclei involved in aspects of visual
      processing and the sleep-wake cycle exhibited specific loss or morphological
      alteration. For all of the neural systems investigated we found nuclei that can
      be considered direct homologues of those found in the laboratory rat. There was
      no specific loss of any nuclear group of any of the systems investigated, but
      there was significant reduction (as judged qualitatively) in the number of
      neurons in the visual associated nuclei. The fact that we could identify all
      nuclear groupings from three systems in this species is suggestive of an
      evolutionary constraint acting at the level of the organization of the neural
      system.

PMID- 16289498
TI  - Is supplementation with elemental diet feasible in patients undergoing pelvic
      radiotherapy?
AB  - BACKGROUND: Acute gastrointestinal upset occurs in approximately 80% of patients
      undergoing radiotherapy for pelvic cancers. Underlying changes relate to
      denudation of the mucosal layer which renders the small intestine vulnerable to
      additional damage from proteolytic enzymes and bile acids. Severe acute bowel
      symptoms may predispose to progressive fibrotic and ischaemic changes. Elemental
      diet given during treatment may reduce acute and chronic bowel symptoms induced
      by pelvic radiotherapy. METHODS: This study aimed to assess compliance with
      elemental diet during pelvic radiotherapy. Patients with gynaecological,
      urological or rectal malignancy undergoing radical or adjuvant pelvic
      radiotherapy were randomised to one of five groups. Each group was assigned a
      target quantity of three different elemental sip feeds (Group 1, 20%, Group 2,
      50%, Group 3, 75% of calorie requirements taken as E028 extra liquid; Group 4,
      50% of calorie requirements taken as E028 extra powder; Group 5, 50% of calorie
      requirements taken as Emsogen powder). Compliance was assessed using a diary card
      and weekly assessment. Statistical analyses were conducted on an intention to
      treat basis. RESULTS: Fifty patients (44 female, six male) mean age 58 yr (95% CI
      55-61), were recruited to the study (24 endometrial, 17 cervical, 7 rectal, 1
      vulval and 1 bladder carcinoma). Mean weight at baseline was 74.5 kg (95% CI 69
      80) and this did not change during treatment. Full compliance was achieved in
      three patients, all from Group 1. By week 5, only 46% of patients were consuming
      elemental diet. Post hoc analysis of variance with repeated measures indicated
      that there were no significant differences in volume of elemental diet consumed
      between groups (P = 0.937). There was a significant inverse linear relationship
      between intake of elemental diet and time (P < 0.001). CONCLUSIONS: Different
      formulations of elemental diet do not influence compliance. Patients are unlikely
      to be able to consume more than one-third of their calorie requirements in the
      form of an elemental sip feed. Further investigation is warranted to determine if
      intervention with this volume of elemental diet is beneficial.

PMID- 16289500
TI  - The 3D structure of the anticancer prodrug CPT-11 with Torpedo californica
      acetylcholinesterase rationalizes its inhibitory action on AChE and its
      hydrolysis by butyrylcholinesterase and carboxylesterase.
AB  - The anticancer prodrug CPT-11 is a highly effective camptothecin analog that has
      been approved for the treatment of colon cancer. The 2.6 angstroms resolution
      crystal structure of its complex with Torpedo californica acetylcholinesterase
      (TcAChE) demonstrates that CPT-11 binds to TcAChE and spans its gorge similarly
      to the Alzheimer drug, Aricept. The crystal structure clearly reveals the
      interactions, which contribute to the inhibitory action of CPT-11. Modeling of
      the complexes of CPT-11 with mammalian butyrylcholinesterase and
      carboxylesterase, both of which are known to hydrolyze the drug, shows how
      binding to either of the two enzymes yields a productive substrate-enzyme
      complex.

PMID- 16289501
TI  - Acetylcholinesterase and molecular interactions at the neuromuscular junction.
AB  - The efficiency and the tight control of neurotransmission require the
      accumulation of synaptic proteins in discrete domains. In neuromuscular
      junctions, the main form of acetylcholinesterase (AChE) is a hetero-oligomer in
      which the catalytic subunits are associated to a specific collagen, ColQ. This
      structural protein is responsible for the insertion and the accumulation of AChE
      in the synaptic basal lamina. We have analyzed the time-course of
      acetylcholinesterase and acetylcholine receptors (AChR) mRNAs during mouse muscle
      cell differentiation in culture. In parallel, we have visualized the formation of
      AChE and AChR aggregates. We show that AChR clusters form first which correlates
      with high gamma-subunit mRNA levels. Then, AChE clusters appear with the onset of
      contraction and correlate with a dramatic increase in AChE, ColQ1 and ColQ1A mRNA
      levels in muscle cells. At that stage, AChR gamma-subunit levels drop while the
      expression level of epsilon-subunits increase. AChE aggregates are organized by a
      ternary complex, which involves direct interactions between ColQ, perlecan and
      MuSK.

PMID- 16289502
TI  - Maternal coffee and alcohol consumption during pregnancy, parental smoking and
      risk of childhood acute leukaemia.
AB  - INTRODUCTION: We investigated the role of maternal alcohol and coffee drinking
      and parental smoking on the risk of childhood acute leukemia in a multicenter
      case-control study. METHODS: The study included 280 incident cases and 288
      hospitalized controls, frequency matched with the cases by age, gender and
      center. Data collection was completed by face-to-face standardized interviews of
      the case and control mothers. RESULTS: An association with maternal alcohol
      consumption during pregnancy was observed with acute lymphoid leukemia (ALL)
      (OR=2.0 [1.4-3.0]) and acute non-lymphoid leukemia (ANLL) (OR=2.6 [1.2-5.8]).
      Maternal coffee consumption during pregnancy was associated with childhood acute
      leukemia, ORs increasing in ALL with coffee consumption (OR=1.1 [0.7-1.8], OR=2.4
      [1.3-4.7] and OR=3.1 [1.0-9.5], respectively, for < or =3, 4-8 and >8 cups/day).
      No association with maternal smoking during pregnancy or parental smoking before
      or after the index child's birth was observed. DISCUSSION: Our results suggest an
      association with maternal alcohol and coffee drinking during pregnancy and call
      for further investigations. Besides, the present study does not support the
      hypothesis of an increase in the risk of childhood leukemia related to parental
      smoking.

PMID- 16289503
TI  - TP53 codon 72 polymorphism and risk of conjunctival squamous cell carcinoma in
      Uganda.
AB  - BACKGROUND: The most common TP53 gene polymorphism, which alters the amino acid
      sequence of the oncosuppressor p53 protein, is located at the codon 72, resulting
      in either Pro72 or Arg72 p53 variant. Several studies have associated this
      polymorphism with different types of cancer. We have analyzed the distribution
      and the role of TP53 Arg72 and Pro72 alleles in conjunctival neoplasia. METHOD:
      The study included 41 invasive conjunctival squamous cell carcinoma (ICSCC), 33
      conjunctival intraepithelial neoplasia of grade 3 (CIN3), 33 of moderate grade
      (CIN1 and CIN2), and 115 controls from Uganda, a sub-Saharan country with the
      highest incidence rate of conjunctival neoplasia in the World, particularly in
      the era of AIDS. The TP53 Arg/Arg codon 72 genotype was detected in 21.9% of
      ICSCC and in 18.2% of CIN3 but only in 6% of CIN1-2 and in 5.2% of controls
      (P<0.05). RESULTS: These data show an increased risk of ICSCC (odds ratio
      (OR)=6.2, 95% confidence interval (CI): 1.6-24.6) and CIN3 (OR=4.1, 95% CI: 1.0
      18.0) associated with TP53 Arg homozygosity, not observed in CIN1-2 lesions
      (OR=0.8, 95% CI: 0.1-5.1). Moreover, the frequency of the Arg homozygosity was
      similar in HIV-positive and HIV-negative groups. We conclude that TP53 Arg/Arg
      codon 72 genotype is a relevant risk factor for invasive squamous cell carcinoma
      of the conjunctiva and for CIN3 in the Ugandan population. DISCUSSION: The
      absence of statistically significant difference in the distribution of TP53 Arg72
      or Pro72 encoding alleles between HIV-positive and -negative subjects, affected
      by conjunctival neoplasia, suggests that HIV infection and/or the associated
      immunodeficiency represent further independent risk factors for ICSCC.

PMID- 16289504
TI  - An association between human papillomavirus 16/18 deoxyribonucleic acid in
      peripheral blood with p16 protein expression in neoplastic cervical lesions.
AB  - BACKGROUND: Human papillomavirus (HPV) infection plays a crucial role in cervical
      carcinogenesis. Apart from the detection of p16 protein in cervical tissues, the
      feasibility of the presence of HPV DNA in peripheral blood being an auxiliary
      marker of cervical lesions was examined. METHODS: Peripheral blood samples and
      cervical tissues, from 36 cervical tissues from high-grade squamous
      intraepithelial lesions (HSIL) and 31 early invasive cervical cancers (EICC),
      were analyzed for HPV 16/18 DNA and HPV 16/18 E7 mRNA expression, as well as the
      in situ expressions of p16 and pRb to investigate the in-between associations.
      RESULTS: The prevalence of HPV 16/18 DNA in patients with EICC was relatively
      higher than those of HSIL, in both of cervical tissues and peripheral blood. The
      presence of HPV 16/18 DNA in peripheral blood was positively correlated with that
      in cervical tissue, as well as with p16 overexpression in cervical tissues
      together with a significant correlation between E7 mRNA and pRb and p16 protein
      expressions. DISCUSSION: A positive correlation between the presence of HPV 16 or
      18 DNA in peripheral blood and p16 overexpression in tissues of patients with
      cervical lesions was confirmed. Together with p16 immunostaining in cervical
      tissues, the detection of high-risk HPV 16 or 18 DNA in peripheral blood may act
      as an auxiliary biomarker for HPV-associated neoplastic cervical lesions.

PMID- 16289505
TI  - Validity of serum pepsinogen levels and quininium resin test combined for gastric
      cancer screening.
AB  - BACKGROUND: To investigate the feasibility of combining several serum markers
      into a valid serum screening tool for gastric cancer, we performed a study
      evaluating the association between gastric cancer and precancerous conditions and
      a blood test for gastric acidity (the blood quininium resin test [QRT]) combined
      with serum pepsinogen levels. METHODS: We performed immunoradiometric assays of
      serum pepsinogen I (PG I), II (PG II) levels, and QRT's in 10 endoscopically
      normal subjects, in 20 patients with chronic atrophic gastritis, and in 13
      patients with biopsy-confirmed gastric adenocarcinoma. RESULTS: Serum PG I, II
      levels, I/II ratio were significantly different among normal, gastritis, and
      cancer patients. Serum PG I/II ratios were much lower in cancer patients. Serum
      quinine levels by QRT were correlated with PG I/II ratio (rs=0.39, p<0.01). Age
      was negatively correlated both with PG I/II ratio (rs=-0.58, p<0.01) and serum
      quinine level (rs=-0.45, p<0.01). The screening using serum PG levels was more
      valid (sensitivity of 69%, specificity of 77%) than that using QRT alone. The
      combination of serum PG levels and QRT increased specificity for detecting
      gastric cancer to 87% without altering sensitivity. CONCLUSION: Although blood
      QRT is a useful addition to other serum screening tests for gastric cancer, these
      tests alone are not sufficiently accurate as screening tools for gastric cancer.

PMID- 16289506
TI  - Effects of CpG ODN on CD4+ and CD8+ T subpopulations in the immune response to
      porcine reproductive and respiratory syndrome killed virus vaccine.
AB  - CpG ODN is a noval immunostimulatory reagent In this research, the effects of
      immunostimulatory CpG oligodeoxynucleotides (CpG ODN) on CD4+ and CD8+ T
      lymphocytes subpopulations in the newborn piglets blood were tested at different
      time with porcine reproductive and respiratory syndrome killed virus vaccine
      (PRRS vaccine) with or without CpG ODN. The results suggested that, the CD4+/CD8+
      ratio decreased with age in piglets inoculated with vaccine alone or GpC ODN with
      vaccine or phosphate buffer saline (PBS), however, it was stable in piglets co
      inoculated with CpG ODN and PRRS vaccine (p>0.05), the use of CpG ODN can prevent
      effectively the reduction of the proportion of CD4+ T lymphocytes. High titers of
      PRRS specific antibody can also be tested in the newborn piglets serum immunized
      PRRS vaccine and CpG ODN (p<0.05).

PMID- 16289507
TI  - Cis-9, trans- 11 and trans-10, cis-12 conjugated linoleic acid (CLA) do not
      affect the plasma lipoprotein profile in moderately overweight subjects with LDL
      phenotype B.
AB  - BACKGROUND: Results of a pilot study suggested that cis-9, trans-11 conjugated
      linoleic acid (CLA) improved LDL phenotype in moderately overweight subjects with
      LDL phenotype B. OBJECTIVE: Initiated by the results of this pilot study, we have
      specifically designed a study to test the hypothesis that cis-9, trans-11
      conjugated linoleic acid improves LDL phenotype in moderately overweight subjects
      with LDL phenotype B. Effects on the serum lipid profile, on plasma glucose and
      insulin concentrations, and on clinical parameters were also examined. DESIGN:
      Volunteers with LDL phenotype B were divided into three groups consuming daily a
      drinkable dairy product not enriched with CLA (placebo, n = 34), the same dairy
      product enriched with 3g c9, t11 CLA (n = 34), or the dairy product enriched with
      3g t10, c12 CLA (n = 19) for 13 weeks. RESULTS: Median changes in the proportions
      of plasma small dense LDL were -2.0% in the control group and -0.1% in the c9,
      t11 CLA and t10, c12 CLA groups (p = 0.981 for the differences between the
      groups). c9, t11 CLA or t10, c12 CLA did also not affect serum concentrations of
      LDL and HDL cholesterol, and of triacylglycerol, and plasma concentrations of
      glucose and insulin. CONCLUSIONS: In humans with LDL phenotype B, c9, t11 CLA and
      t10, c12 CLA do not beneficially change risk factors for cardiovascular disease
      or diabetes.

PMID- 16289508
TI  - Small animal positron emission tomography during vagus nerve stimulation in rats:
      a pilot study.
AB  - Vagus nerve stimulation (VNS) is an effective neurophysiological treatment for
      patients with refractory epilepsy, however, the mechanism of action remains
      unclear. Small animal positron emission tomography (PET) permits the monitoring
      of biochemical processes during multiple scans in the same animal. The aim of
      this pilot study was to explore the potential of 2-[18F]-fluoro-2-deoxy-d-glucose
      (FDG)-PET to investigate the effect of acute and chronic VNS on glucose
      metabolism in the rat brain. One week after EEG and VNS electrode implantation, a
      baseline FDG-PET scan was acquired during which animals were not stimulated.
      Secondly, scans were taken after first activation of the VNS electrode (acute
      VNS) and after one week of continuous VNS (chronic VNS). On the same time points,
      images were obtained in a control group. After acquisition, PET images were
      manually fused with MRI data. Normalized brain activities and left/right activity
      ratios of different brain structures were compared between control measurements
      and VNS group. During acute VNS, glucose metabolism was significantly decreased
      in the left hippocampus (P<0.05). Significant increases were found in both
      olfactory bulbs (P<0.05). During chronic VNS, a significant decrease in
      left/right ratio in the striatum (P<0.05) was found. Acute and chronic VNS
      induced changes in glucose metabolism in regions important for seizure control
      (hippocampus and striatum). Our results promote further brain research on VNS
      using small animal PET in rats.

PMID- 16289509
TI  - Effects of zonisamide on neurotransmitter exocytosis associated with ryanodine
      receptors.
AB  - To clarify the antiepileptic and neuroprotective actions of zonisamide (ZNS), we
      determined acute effects of ZNS on exocytosis of GABA and glutamate associated
      with ryanodine-receptor (Ryr) in rat hippocampus using microdialysis. ZNS
      increased basal GABA release concentration-dependently without affecting basal
      glutamate release; however, K(+)-evoked glutamate and GABA releases were reduced
      by ZNS concentration-dependently. Inhibition of Ryr reduced K(+)-evoked GABA and
      glutamate releases without affecting their basal releases. Ryanodine affected
      GABA and glutamate releases biphasic concentration-dependently: lower
      concentration of ryanodine increased both basal and K(+)-evoked releases of GABA
      and glutamate, whereas higher concentration reduced them. The therapeutically
      relevant concentration of ZNS inhibited ryanodine-induced GABA and glutamate
      releases, and abolished the inflection point in concentration-response curve for
      ryanodine on neurotransmitter exocytosis. These data suggest that ZNS elevates
      seizure threshold via enhancement of GABAergic transmission during resting stage.
      ZNS inhibits propagation of epileptic hyperexcitability and Ryr-associated
      neuronal damage during neuronal hyperexcitable stage. These demonstrations
      indicate that the indirect inhibition of Ryr activities by ZNS during neuronal
      hyperexcitability appear to be involved in the mechanisms of action of
      antiepileptic and neuroprotective actions of ZNS.

PMID- 16289510
TI  - Determination of the origin of unknown irradiated nuclear fuel.
AB  - An isotopic fingerprinting method is presented to determine the origin of unknown
      nuclear material with forensic importance. Spent nuclear fuel of known origin has
      been considered as the 'unknown' nuclear material in order to demonstrate the
      method and verify its prediction capabilities. The method compares, using factor
      analysis, the measured U, Pu isotopic compositions of the 'unknown' material with
      U, Pu isotopic compositions simulating well known spent fuels from a range of
      commercial nuclear power stations. Then, the 'unknown' fuel has the same origin
      as the commercial fuel with which it exhibits the highest similarity in U, Pu
      compositions.

PMID- 16289511
TI  - Hydrolysis by phospholipase D of phospholipids in solution state or adsorbed on a
      silica matrix.
AB  - Phospholipases D (PLD) catalyse hydrolysis and transphosphatidylation reactions
      in phospholipids. In the present study, the hydrolytic activity for cabbage PLD
      was investigated with five different substrates
      (dipalmitoylphosphatidylethanolamine (DPPE), dipalmitoylphosphatidylcholine
      (DPPC), didecanoylphosphatidylcholine (DDPC), 1-alkyl-2-acetyl-sn-glycero-3
      phosphocholine and lyso-phosphatidylcholine (lyso-PC)) in solution or adsorbed on
      a silica matrix. In the specific buffer solutions, where the substrates were
      proved to form large multilamellar polydisperse aggregates, PLD showed preference
      for DPPC > DPPE > DDPC > 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine > lyso-PC.
      When the substrates were adsorbed on the silica matrix, PLD hydrolysed 1-alkyl-2
      acetyl-sn-glycero-3-phosphocholine and lyso-PC, DDPC, but not DPPC or DPPE.
      Theoretical studies of the simplest possible adducts between the phospholipids
      and the silica matrix were performed. Examination of local geometries of DPPC
      showed a significant blocking of the P-O-X bond-prone to hydrolysis, which could
      possibly block the access of PLD. Immobilization of phospholipids could be
      applied for improving the yield of reactions catalysed by PLD as well as for
      performing a targeted production of short-chain length phosphatidic acid analogs.

PMID- 16289513
TI  - Current state of three-dimensional characterisation of antifungal targets and its
      use for molecular modelling in drug design.
AB  - The alarming rise in life-threatening systemic fungal infections due to the
      emergence of drug-resistant fungal strains had produced an increased demand for
      new antimycotics, especially those targeting novel antifungal structures. Drug
      discovery has developed from screening natural products and chemical synthesis to
      a modern approach, namely structure-based drug design. Whilst many antifungal
      agents currently in use were discovered more than 30 years ago, characterisation
      of various drug targets has only been achieved recently, contributing immensely
      to understanding the structure-activity relationships of antifungals and their
      targets. Three-dimensional characterisation has become a well established tool
      for modern antifungal drug research and should play an important role in
      investigations for new antifungal agents.

PMID- 16289514
TI  - Linezolid reduces length of stay and duration of intravenous treatment compared
      with vancomycin for complicated skin and soft tissue infections due to suspected
      or proven methicillin-resistant Staphylococcus aureus (MRSA).
AB  - We compared the health outcomes in patients treated with linezolid or vancomycin
      for complicated skin and soft tissue infections (cSSTIs). This analysis is part
      of a randomised, open-label, multinational trial involving 1200 adult patients
      hospitalised with cSSTIs due to suspected or proven methicillin-resistant
      Staphylococcus aureus (MRSA). Subjects received linezolid 600 mg intravenous
      (i.v.) or oral, or vancomycin 1g i.v. every 12 h. A test-of-cure was assessed at
      7 days post therapy. Compared with vancomycin, linezolid treatment was associated
      with significantly shorter length of stay (all P < 0.01), decreased i.v.
      antibiotic treatment duration (all P < 0.0001) and higher discharge rates (all P
      < 0.05). Thus, linezolid has the potential to reduce medical resource use for the
      treatment of cSSTIs.

PMID- 16289515
TI  - Temporal development of hippocampal cell death is dependent on tissue strain but
      not strain rate.
AB  - Deformation of brain tissue in response to mechanical loading of the head is the
      root-cause of traumatic brain injury (TBI). Even below ultimate failure limits,
      deformation activates pathophysiological cascades resulting in delayed cell
      death. Injury response of soft tissues, such as the chest and spinal cord, is
      dependent on the product of deformation and velocity, a parameter termed the
      viscous criterion. We set out to test if hippocampal cell death could be
      predicted by a similar combination of strain and strain rate and if the viscous
      criterion was valid for hippocampus. Quantitative prediction of the brain's
      biological response to mechanical stimuli is difficult to achieve in animal
      models of TBI, so we utilized an in vitro model of TBI based on hippocampal slice
      cultures. We quantified the temporal development of cell death after precisely
      controlled deformations for 30 combinations of strain (0.05-0.50) and strain rate
      (0.1-50s(-1)) relevant to TBI. Loading conditions for a subset of cultures were
      verified by analysis of high-speed video. Cell death was found to be
      significantly dependent on time-post injury, on strain magnitude, and to a lesser
      extent, on anatomical region by a repeated-measures, three-way ANOVA. The
      responses of the CA1 and CA3 regions of the hippocampus were not statistically
      different in contrast to some in vivo TBI studies. Surprisingly, cell death was
      not dependent on strain rate leading us to conclude that the viscous criterion is
      not a valid predictor for hippocampal tissue injury. Given the large data set and
      extensive combinations of biomechanical parameters, predictive mathematical
      functions relating independent variables (strain, region, and time post-injury)
      to the resultant cell death were defined. These functions can be used as
      tolerance criteria to equip finite element models of TBI with the added
      capability to predict biological consequences.

PMID- 16289516
TI  - Kinetic asymmetry in female runners with and without retrospective tibial stress
      fractures.
AB  - Gait asymmetry may be linked to the tendency for runners to sustain chronic
      overuse injuries. This paper compares gait asymmetry in female runners who have
      never sustained a running-related injury to those who have sustained unilateral
      tibial stress fractures. The symmetry index was used to characterize asymmetry in
      the kinetics of both subject groups. There were three aims to this study: (1) to
      report natural levels of asymmetry for healthy, never-injured female runners, (2)
      to compare asymmetry levels between never-injured runners and those who have
      sustained stress fractures, and (3) to examine the kinetics between the involved
      and uninvolved limbs of runners who have sustained stress fractures. In all three
      aims, peak medial, lateral, braking, vertical impact, and vertical ground
      reaction forces, average and peak instantaneous vertical loading rates, and peak
      shock were examined. In the never-injured runner group, natural levels of
      asymmetry ranged from 3.1% for peak vertical ground reaction force up to 49.8%
      for peak lateral ground reaction force. Symmetry indices were not significantly
      different in the runners who had previously sustained stress fractures. The
      involved limb of the previously injured runners demonstrated higher values for
      braking and vertical impact ground reaction force and peak shock. Interestingly,
      these runners appeared to have bilaterally-elevated lateral ground reaction
      forces and loading rates as compared to the never-injured group, although this
      was not statistically tested. This suggests that previously injured runners may
      be closer to the injury threshold and, thus, more susceptible. Asymmetry may
      simply influence the side on which they become injured.

PMID- 16289517
TI  - Effects of delays on human performance on a temporal discrimination procedure:
      evidence of a choose-short effect.
AB  - Studies of temporal discrimination in non-human subjects have reliably shown a
      choose-short effect: higher matching accuracy on short-duration-sample trials
      than on long-duration-sample trials. This effect occurs as a function of
      increasing the delay between the onset of sample and comparison stimuli in a
      delayed matching-to-sample procedure. The present experiment investigated whether
      the choose-short effect could be demonstrated in human subjects under conditions
      which paralleled those used with non-human subjects. Subjects responded under a
      discrete-trial procedure in which they were required to push one of two buttons
      depending on the duration of a sample stimulus (a blue square on a computer
      monitor). Delays (0, 8, 16, and 32s) separated sample and comparison stimuli (two
      white boxes) and were tested both within and across several sessions.
      Intermediate durations (probe stimuli between 2 and 4s) were also presented. The
      addition of a delay between the sample and comparison stimuli produced a bias to
      judge intervals as short when the 8 and 32-s delays were tested across sessions
      and when the 0, 16, and 32-s delays were tested within the same session. Thus,
      the choose-short effect was produced in human subjects using the interval
      bisection procedure regardless of delay length.

PMID- 16289518
TI  - The effect of heel-pad thickness and loading protocol on measured heel-pad
      stiffness and a standardized protocol for inter-subject comparability.
AB  - BACKGROUND: Heel-pad stiffness is an important parameter in clinical assessments
      of the lower limb and is usually quantified by the slope of the force-deformation
      curve. However, the data produced is affected by the geometry of the heel, thus
      making inferences about tissue behaviour difficult. METHOD: With the use of
      finite element analysis the aim of this study is to explore the possibility of
      expressing heel-pad stiffness in terms of stress-strain data. An axisymmetric,
      non-linear and time-dependent representation of the heel was created. The
      material model, incorporating non-linearity and viscoelasticity, was based on a
      series of experiments involving healthy, cadaveric specimens and loading at
      different loading rates (0, 175 and 350 mm/s). The conditions of an in vivo study
      were then replicated and stress-strain data of the model were compared. Good
      agreement was achieved (error <5%) at higher strains (>0.2). Probe diameter,
      loading rate and heel-pad thickness were then varied and heel-pad stiffness,
      expressed in terms of both force-deformation and stress-strain characteristics,
      reported. FINDINGS: In terms of the force-deformation characteristics, thin heels
      are consistently stiffer than thick heels. In terms of stress-strain
      characteristics, thicker heels are stiffer than thin heels using small probes
      whereas thinner heels are stiffer than thick heels using large probes. It was
      possible to predict stress-strain data of the heel-pad that are least-dependent
      of heel-pad thickness using large probes and slow-rising loads. INTERPRETATION:
      It is suggested that stress-strain curves derived from large probes under slow
      loads would provide the most robust and standardized measure of heel-pad
      stiffness.

PMID- 16289519
TI  - Investigation in thorium phosphate by NMR II-phosphorus dipolar networks.
AB  - With through space and through bond experiments in two-dimensional NMR we analyze
      the transformation from the thorium phosphate-hydrogen phosphate hydrate (TPHPH)
      to the beta form of the thorium phosphate diphosphate (beta-TPD) in relation with
      the phosphorus networks. These techniques are complementary: the through space
      coupling gives an insight on the dipolar phosphorus networks while the through
      bond coupling is particularly efficient in the detection of the P2O7 groups. With
      these experiments we show that in a first step, by heating the precursor TPHPH
      above 250 degrees C, it transforms into an alpha form of TPD. This transformation
      is due to the complete condensation of hydrogen phosphate groups HPO4 into P2O7
      entities. By heating alpha-TPD above 950 degrees C it transforms into its well
      known beta form. The alpha form is characterized by a hygroscopic behavior: some
      water molecules are present near the P2O7 groups that makes non-equivalent their
      phosphorus nuclei. PO4 dipolar networks are always present in the alpha form. The
      main effect of these PO4 and P2O7 units is to give the system a channel structure
      and the water enters in them.

PMID- 16289520
TI  - Efficient spin-spin scalar coupling mediated C-13 homonuclear polarization
      transfer in biological solids without proton decoupling.
AB  - We demonstrate that an efficient C' <--> C alpha polarization transfer based on J
      coupling can be realized under fast magic-angle spinning (MAS) condition without
      1H decoupling. Experimental results are presented for model crystalline compounds
      as well as a non-crystalline 17-residue polypeptide MB(i + 4)EK. Measurements on
      MB(i + 4)EK demonstrate that 53% of the initial C' polarization was transferred
      to the cross peaks at 7.05 T under 25 kHz MAS spinning.

PMID- 16289521
TI  - Solid-state NMR and 2,3-dicyano-5,7-dimethyl-6H-1,4-diazepine.
AB  - Crystalline 2,3-dicyano-5,7-dimethyl-6H-1,4-diazepine (A) was investigated by
      solid-state NMR spectroscopy, X-ray diffraction, and spectral simulations. The
      solid-state 13C NMR spectra of A display peculiar splittings for the methyl and
      cyano resonances. The crystal structure of A indicates that the methyl doublet is
      a consequence of two crystallographically inequivalent environments. The methyl
      motions associated with each site was examined via spin-lattice relaxation time
      (T1) measurements, and the carbon relaxation times (T(1)C) were used to calculate
      energy barriers to methyl rotation. The energy barriers to rotation were then
      used to correlate each methyl 13C shift with a particular crystallographic
      environment. The complex cyano splittings, however, are a result of both
      crystallographic inequivalence and residual 13C-14N dipolar coupling. The
      multiplet patterns of the isotropic shifts (centerbands) are dependent upon the
      magic-angle spinning (MAS) rate. Spectral simulations, using the perturbation
      method, of the centerbands and first-order sidebands were used to demonstrate,
      and elucidate, the observed MAS rate-dependent multiplet patterns of the cyano
      signals.

PMID- 16289522
TI  - TAF4b, a TBP associated factor, is required for oocyte development and function.
AB  - Development of a fertilizable oocyte is a complex process that relies on the
      precise temporal and spatial expression of specific genes in germ cells and in
      surrounding somatic cells. Since female mice null for Taf4b, a TBP associated
      factor, are sterile, we sought to determine when during follicular development
      this phenotype was first observed. At postnatal day 3, ovaries of Taf4b null
      females contained fewer (P < 0.01) oocytes than ovaries of wild type and
      heterozygous Taf4b mice. However, expression of only one somatic cell marker
      Foxl2 was reduced in ovaries at day 15. Despite the reduced number of follicles,
      many proceed to the antral stage, multiple genes associated with granulosa cell
      differentiation and oocyte maturation were expressed in a normal pattern, and
      immature Taf4b null females could be hormonally primed to ovulate and mate.
      However, the ovulated cumulus oocyte complexes from the Taf4b null mice had fewer
      (P < 0.01) cumulus cells, and the oocytes were functionally abnormal. GVBD and
      polar body extrusion were reduced significantly (P < 0.01). The few oocytes that
      were fertilized failed to progress beyond the two-cell stage of development.
      Thus, infertility in Taf4b null female mice is associated with defects in early
      follicle formation, oocyte maturation, and zygotic cleavage following ovulation
      and fertilization.

PMID- 16289523
TI  - Using latent class analysis to identify patterns of hepatitis C service provision
      in drug-free treatment programs in the U.S.
AB  - Hepatitis C virus (HCV) infection is a global health problem, and in many
      countries (including the U.S.), illicit drug users constitute the group at
      greatest risk for contracting and transmitting HCV. Drug treatment programs are
      therefore unique sites of opportunity for providing medical care and support for
      many HCV infected individuals. This paper determines subtypes of a large sample
      of U.S. drug-free treatment programs (N=333) according to services they provide
      to patients with HCV infection, and examines the organizational and aggregate
      patient characteristics of programs in these subtypes. A latent class analysis
      identified four subtypes of HCV service provision: a "Most Comprehensive
      Services" class (13% of the sample), a "Comprehensive Off-Site Medical Services"
      class (54%), a "Medical Monitoring Services" class (8%) and a "Minimal Services"
      class (25%). "Comprehensive" services class programs were less likely to be
      outpatient and private for profit than those in the other two classes. It is of
      concern that so many programs belong to the "Minimal Services" class, especially
      because some of these programs serve many injection drug users. "Minimal
      Services" class programs in the U.S. need to innovate services so that their HCV
      infected patients can get the medical and support care they need. Similar
      analyses in other countries can inform their policy makers about the capacity of
      their drug treatment programs to provide support to their HCV infected patients.

PMID- 16289524
TI  - Maturation of outcomes of behavioral and electrophysiologic tests of central
      auditory function.
AB  - The human peripheral auditory system is fully developed at birth; however,
      myelination continues for several years in the higher auditory pathways. The aim
      of the present study was to assess the maturation course of the frequency and
      duration pattern tests and the middle latency response (MLR). One hundred and
      fifty normal participants ranging from 7 to 16 years of age were tested using
      conventional protocols. Results showed increased performance with increased age
      on both the behavioral tests up to age 12. However, there was no significance
      change across this age range for either latency or amplitude measures on the MLR.
      The MLR showed less variability for older children. High variability was a likely
      factor for the statistical outcome of the MLR. The data obtained on the frequency
      and duration pattern tests were applied to the development of age related norms.
      LEARNING OUTCOMES: As a result of this experience, the reader will obtain
      information about (a) the normal development of the auditory system; (b)
      performance of children on several standard tests of auditory function; and (c)
      the characteristics of MLRs in the same group of children.

PMID- 16289525
TI  - Effects of oral androstenedione on phospholipid fatty acids, ATP, caspase-3,
      prostaglandin E(2) and C-reactive protein in serum and livers of pregnant and non
      pregnant female rats.
AB  - Androstenedione, a steroidal dietary supplement taken to enhance athletic
      performance, could affect serum and liver lipid metabolism, induce liver toxicity
      or alter inflammatory response depending on dose and duration of exposure.
      Pregnancy could further exaggerate these effects. To examine this, mature female
      rats were gavaged with 0, 5, 30 or 60 mg/kg/day androstenedione beginning two
      weeks prior to mating and continuing through gestation day 19. Non-pregnant
      female rats were gavaged over the same time frame with 0 or 60 mg/kg/day
      androstenedione. Serum was collected and livers were removed from dams on
      gestation day 20 and from non-pregnant rats after 5 weeks of treatment.
      Androstenedione had no effect on serum total cholesterol, triglycerides or HDL
      cholesterol, but significantly decreased C-reactive protein in pregnant rats and
      prostaglandin E(2) in serum of both pregnant and non-pregnant rats. There were
      treatment related decreases in liver ATP and, to a lesser degree, caspase-3 and
      no change in alkaline phosphatase of pregnant female rats. Androstenedione
      decreased docosahexaenoic acid in both serum and liver phospholipids of pregnant
      female rats. In conclusion, oral androstenedione did not result in overt
      hepatotoxicity in pregnant female rats, but produced modest changes in lipid
      metabolism and may impair regeneration of injured hepatic cells or tissue.

PMID- 16289526
TI  - Event-related theta oscillations during working memory tasks in patients with
      schizophrenia and healthy controls.
AB  - Altered frontal lobe activity and executive control associated with working
      memory (WM) dysfunction are recognized as core deficits in schizophrenia. These
      impairments have been discussed as being associated with deficits in self
      regulated action monitoring and anticipatory action plan generation. To study
      electrophysiological correlates of executive control -- specifically action
      monitoring and action rule switching -- under varying WM load, we used a paradigm
      derived from classic N-back (WM) tasks and requiring monitoring of simple
      actions. We focused on event-related changes in post-stimulus theta oscillatory
      activity during varying cognitive and WM demand in healthy controls and
      schizophrenia patients. The results show significant WM load and rule-switching
      related increases of post-stimulus theta amplitude at fronto-central locations in
      controls. In patients with schizophrenia, there was no such modulation, but --
      apart from an increased early theta at left temporal locations -- generally
      reduced late theta responses in all tasks and at all locations. Furthermore, the
      patients with schizophrenia showed significant differences in their error
      patterns, which imply differences in automation and anticipation of actions
      between controls and patients. These findings suggest that theta oscillations are
      involved in mediating frontal lobe activity and functions related to enhanced
      executive control. We conclude that the patients with schizophrenia showed
      deficits in acquiring a mental task set which appear to be associated with
      impairments in action monitoring and task-specific regulation of executive
      control.

PMID- 16289527
TI  - Adaptive expression pattern of different proteins involved in cellular calcium
      homeostasis in denervated rat vas deferens.
AB  - The activity and protein expression of plasma membrane and sarco(endo)plasmic
      reticulum (Ca2+-Mg2+)ATPases and ryanodine receptors were investigated in
      surgically denervated rat vas deferens. The function of thapsigargin-sensitive
      but not thapsigargin-resistant (Ca2+-Mg2+)ATPase (from sarco(endo)plasmic
      reticulum and plasma membrane, respectively), evidenced by enzyme activity and
      Ca2+ uptake experiments, was significantly depressed by 30-50% when compared to
      innervated vas. Western blots showed that such reduction in sarco(endo)plasmic
      reticulum (Ca2+-Mg2+)ATPase performance was accompanied by a decrement of similar
      magnitude in sarco(endo)plasmic reticulum (Ca2+-Mg2+)ATPase type 2 protein
      expression, without any significant change in plasma membrane (Ca2+-Mg2+)ATPase
      expression. Finally, [3H]ryanodine binding revealed that the density of ryanodine
      binding sites was reduced by 45% after denervation without modification in
      affinity. The present findings demonstrate that sarco(endo)plasmic reticulum
      proteins involved in intracellular calcium homeostasis are clearly down-regulated
      and brings further evidence of a modified calcium translocation in denervated rat
      vas deferens.

PMID- 16289528
TI  - KR-32570, a novel Na+/H+ exchanger-1 inhibitor, attenuates hypoxia-induced cell
      death through inhibition of intracellular Ca2+ overload and mitochondrial death
      pathway in H9c2 cells.
AB  - A novel Na+/H+ exchanger-1 (NHE-1) inhibitor [5-(2-methoxy-5-chloro-5
      phenyl)furan-2-ylcarbonyl]guanidine (KR-32570) has been previously demonstrated
      to elicit cardioprotective effect against ischemic injury in rat heart. In the
      present study, we examined the effects of KR-32570 on cell death induced by
      hypoxic insult in heart-derived H9c2 cells. Treatment with KR-32570 (1-10 microM)
      significantly reduced hypoxia-induced necrotic cell death (lactate dehydrogenase
      release) and apoptotic cell death (TUNEL-positivity, caspase-3 activity). KR
      32570 also decreased the cytosolic and mitochondrial Ca2+ overload induced by
      hypoxia. Inhibition of mitochondrial Ca2+ overload by ruthenium red mimicked the
      anti-apoptotic effect of KR-32570. In addition, KR-32570 significantly recovered
      the large reduction in mitochondrial membrane potential (delta psi(m)) and
      cytochrome c release induced by hypoxia. Taken together, our results suggest that
      a new NHE-1 inhibitor KR-32570 elicits potent cardioprotective effects in H9c2
      cells, and its effects may be mediated by inhibition of intracellular Ca2+
      overload and mitochondrial death pathway during hypoxia.

PMID- 16289529
TI  - Detection of one VH antibody sequence in both healthy donors and urticaria
      patients.
AB  - We have previously isolated anti-FcepsilonRIalpha autoantibodies from phage
      libraries of healthy donors and urticaria patients. Strikingly, the same
      antibody, LTMalpha15, was isolated from both libraries. Sequence analysis
      revealed a germline configuration of the LTMalpha15 variable heavy (V(H)) chain
      with a slightly mutated variable light (V(L)) chain supporting its classification
      as a natural autoantibody. Distribution analysis of anti-FcepsilonRIalpha
      autoantibodies by functional or serological tests delivered conflicting data. For
      this reason we have developed a new real-time PCR to analyse the distribution of
      LTMalpha15V(H) in healthy donors and urticaria patients. Our new bioinformatic
      program permitted the design of a minor groove binder (MGB) TaqMan probe that
      specifically detected the LTMalpha15V(H). We were able to demonstrate a broad
      range of rearranged V(H) gene copy number without any correlation to the state of
      health. Monitoring LTMalpha15V(H) gene copy number in a single donor over a
      period of 70 days revealed a time-related fluctuation of circulating B cells
      carrying LTMalpha15V(H). We propose that our real-time PCR may serve as a model
      for the quantification of natural antibody sequences at a monoclonal level.

PMID- 16289531
TI  - Delivering twins--perceptions and expectations.

PMID- 16289530
TI  - The heme-binding lipoprotein (HbpA) of Haemophilus influenzae: role in heme
      utilization.
AB  - Haemophilus influenzae has an absolute growth requirement for heme and a heme
      binding lipoprotein (HbpA) has been implicated in the utilization of this
      essential nutrient. HbpA was identified by examining clones from an H. influenzae
      genomic library that caused Escherichia coli harboring the clone to bind heme.
      However, HbpA has not been shown to mediate heme acquisition in H. influenzae. We
      constructed an insertional mutation of hbpA in a nontypeable H. influenzae strain
      and demonstrated a role for the gene in utilization of multiple heme sources.
      This is the first report confirming a role for HbpA in utilization of heme.

PMID- 16289532
TI  - Longitudinal reference charts for growth of the fetal head, abdomen and femur.
AB  - OBJECTIVES: The aims of the present study were to establish improved reference
      charts for growth of the fetal head, abdomen and femur, and to determine the
      effect of fetal and maternal factors. STUDY DESIGN: This prospective longitudinal
      study included 650 low-risk pregnancies. Outer-outer biparietal diameter (BPD),
      head circumference (HC), mean abdominal diameter (MAD), abdominal circumference
      (AC) and femur length (FL) were measured by ultrasound, and the statistical
      analysis was based on regression analysis and multilevel modeling. RESULTS:
      Reference percentiles for the growth of MAD, AC and FL showed continuous growth
      in gestational week 10-40, while BPD and HC showed a slightly blunted growth
      toward the end of pregnancy. FL was the only variable that was not influenced by
      gender. There was a significant negative association between breech presentation
      and all five biometrical variables, while maternal weight was positively
      associated with all five variables. Cephalic index significantly influenced BPD
      and HC. Maternal height had a positive effect on BPD, HC, AC and FL, and parity
      had a positive effect on MAD and AC, while smoking influenced negatively HC, MAD,
      and FL. Terms for calculating conditional reference values and customisation for
      individualised growth assessment are presented. CONCLUSIONS: New reference charts
      for the growth of fetal head, abdomen and femur are suggested for assessing fetal
      size and growth, and can be adjusted for maternal and fetal factors to suite
      individual pregnancies.

PMID- 16289533
TI  - Orientation and confinement of cells on chemically patterned polystyrene
      surfaces.
AB  - UV/ozone oxidation was combined with a photomasking technique to produce adjacent
      regions of different chemistry on polystyrene (PS) surfaces. The surface
      chemistry and topography were studied using AFM, XPS and contact angle
      measurements. The physicochemical patterns were visualised by the condensation of
      water vapour upon the surfaces and by the differential attachment of Chinese
      hamster ovarian (CHO) cells. The orientation of CHO cells on 55 and 125 microm
      wide oxidised PS strips were measured and found to be highly dependent on the
      width of the oxidised feature. CHO cells in relatively close proximity to a
      linear polar/non-polar border showed significant axial alignment along the
      border. CHO cells can also be confined to specific regions of the polymer
      surface. Cells attached to larger areas (75 microm x 75 microm) were found to
      have a smaller average cell size than cells attached to the smaller (56 microm x
      56 microm) areas.

PMID- 16289534
TI  - Remating inhibition in female Queensland fruit flies: effects and correlates of
      sperm storage.
AB  - Reproductive success of male insects commonly hinges both on their ability to
      secure copulations with many mates and also on their ability to inseminate and
      inhibit subsequent sexual receptivity of their mates to rival males. We here
      present the first investigation of sperm storage in Queensland fruit flies
      (Tephritidae: Bactrocera tryoni; a.k.a. 'Q-flies') and address the question of
      whether remating inhibition in females is directly influenced by or correlated
      with number of sperm stored from their first mates. We used irradiation to
      disrupt spermatogenesis and thereby experimentally reduce the number of sperm
      stored by some male's mates while leaving other aspects of male sexual
      performance (mating probability, latency until copulating, copula duration)
      unaffected. Females that mated with irradiated rather than normal males were less
      likely to store any sperm at all (50% vs. 89%) and, if some sperm were stored,
      the number was greatly reduced (median 11 vs. 120). Despite the considerable
      differences in sperm storage, females mated by normal males and irradiated males
      were similarly likely to remate at the next opportunity, indicating (1) number of
      sperm stored does not directly drive female remating inhibition and (2) factors
      actually responsible for remating inhibition are similarly expressed in normal
      and irradiated males. While overall levels of remating were similar for mates of
      normal and irradiated males, factors responsible for female remating inhibition
      were positively associated with presence and number of sperm stored by mates of
      normal but not irradiated males. We suggest seminal fluids as the most likely
      factor responsible for remating inhibition in female Q-flies, as these are likely
      to be transported in proportion to number of sperm in normal males, be
      uninfluenced by irradiation, and be transported without systematic relation to
      sperm number in irradiated males.

PMID- 16289535
TI  - Laminopathy-inducing lamin A mutants can induce redistribution of lamin binding
      proteins into nuclear aggregates.
AB  - Lamins, members of the family of intermediate filaments, form a supportive
      nucleoskeletal structure underlying the nuclear envelope and can also form
      intranuclear structures. Mutations within the A-type lamin gene cause a variety
      of degenerative diseases which are collectively referred to as laminopathies. At
      the molecular level, laminopathies have been shown to be linked to a
      discontinuous localization pattern of A-type lamins, with some laminopathies
      containing nuclear lamin A aggregates. Since nuclear aggregate formation could
      lead to the mislocalization of proteins interacting with A-type lamins, we set
      out to examine the effects of FLAG-lamin A N195K and R386K protein aggregate
      formation on the subnuclear distribution of the retinoblastoma protein (pRb) and
      the sterol responsive element binding protein 1a (SREBP1a) after coexpression as
      GFP-fusion proteins in HeLa cells. We observed strong recruitment of both
      proteins into nuclear aggregates. Nuclear aggregate recruitment of the NPC
      component nucleoporin NUP153 was also observed and found to be dependent on the N
      terminus. That these effects were specific was implied by the fact that a number
      of other coexpressed karyophilic GFP-fusion proteins, such as the nucleoporin
      NUP98 and kanadaptin, did not coaggregate with FLAG-lamin A N195K or R386K.
      Immunofluorescence analysis further indicated that the precursor form of lamin A,
      pre-lamin A, could be found in intranuclear aggregates. Our results imply that
      redistribution into lamin A-/pre-lamin A-containing aggregates of proteins such
      as pRb and SREBP1a could represent a key aspect underlying the molecular
      pathogenesis of certain laminopathies.

PMID- 16289536
TI  - Enhancement of superficial pseudohyphal growth by overexpression of the SFG1 gene
      in yeast Saccharomyces cerevisiae.
AB  - In response to nitrogen limitation, diploid yeast strains of Saccharomyces
      cerevisiae undergo a dimorphic transition to a filamentous growth form known as
      pseudohyphal growth. This developmental change can be classified into two
      distinct growing forms: invasive pseudohyphal growth and superficial pseudohyphal
      growth. We identified a yeast gene, SFG1, whose overexpression predominantly
      enhances superficial pseudohyphal growth when starved for nitrogen. Sfg1 has a
      sequence similarity to members of a family of transcriptional regulators of
      fungal development. Cells of a homozygous sfg1/sfg1 diploid strain have a serious
      defect in pseudohyphal growth, indicating that Sfg1 has an essential function for
      pseudohyphal development. Our analyses show that Sfg1 may act separately from
      mitogen-activated protein kinase (MAPK) pathway and cAMP-dependent protein kinase
      A (PKA) pathway.

PMID- 16289537
TI  - The functional evaluation of human peptide/histidine transporter 1 (hPHT1) in
      transiently transfected COS-7 cells.
AB  - Recently, the expression of the human peptide/histidine transporter (hPHT1,
      SLC15A4) mRNA was observed in the GI tract and in Caco-2 cells, suggesting that
      it may participate in the intestinal absorption of peptide-based agents. This
      study aims to elucidate the: (i) protein expression pattern of hPHT1 (SLC15A4) in
      human small intestine; (ii) cloning of the hPHT1 full-length sequence; (iii)
      functional characterization of hPHT1 in transiently transfected COS-7 cells. The
      expression of hPHT1 was measured using Western blot and immunohistochemical
      analysis. The hPHT1 full-sequence was amplified from BeWo cells, inserted into
      the pcDNA3.1-V5/His TOPO plasmid and transiently transfected into COS-7 cells to
      investigate the uptake kinetics of [3H]histidine and [3H]carnosine. Time, pH and
      sodium-dependent uptake studies were performed in mock (empty vector) and hPHT1
      COS-7 cells. Results demonstrated hPHT1 protein expression in different
      intestinal regions. Histidine and carnosine uptake was linear in hPHT1-COS-7
      cells over 15 min and was found to be pH-dependent. These substrates and
      valacyclovir showed significantly higher uptake at pH 5.0 in the hPHT1 transients
      when contrasted to the mock COS-7 cells, whereas glycylsarcosine uptake was
      significantly lower and unaffected by pH. Other di- and tripeptides also showed
      affinity for hPHT1. This study presents the initial functional characterization,
      the protein expression of the hPHT1 transporter and provides insight into a
      potentially different route for increasing peptide and peptide-based drug
      transport.

PMID- 16289538
TI  - Interfacial adsorption of insulin conformational changes and reversibility of
      adsorption.
AB  - The adsorption of human insulin to Teflon particles was studied with respect to
      conformational changes and the reversibility of adsorption was examined by total
      internal reflection fluorescence (TIRF). Adsorption isotherms for the adsorption
      of human insulin indicated high affinity adsorption, even at electrostatic
      repulsive conditions. The plateau value for adsorption was in accordance with a
      protein layer consisting primarily of insulin monomers. Conformational changes of
      the insulin upon adsorption, was investigated by circular dicroism (CD) and
      fluorescence spectroscopy. The results suggested unfolding of adsorbed insulin,
      as observed by a decrease in alpha-helix and increase in random coil
      conformation. The changes in protein structure was not only related to the
      adsorbed species being monomeric, since CD and fluorescence results were
      different for adsorbed insulin compared to a monomeric analog of human insulin.
      Furthermore, the thermal stability in the adsorbed state was changed compared to
      insulin in solution. On the basis of the TIRF studies with FITC-labelled insulin
      it was not possible to firmly conclude whether exchange between human insulin in
      the adsorbed state and in solution takes place, due to the limited time range
      investigated. However, the desorption mechanism appeared to be different with
      unlabelled insulin in the bulk solution compared to phosphate buffer.

PMID- 16289539
TI  - A data mining approach to simulating farmers' crop choices for integrated water
      resources management.
AB  - Water and land resources in Thailand are increasingly under pressure from
      development. In particular, there are many resource conflicts associated with
      agricultural production in northern Thailand. Communities in these areas are
      significantly constrained in the land and water management decisions they are
      able to make. This paper describes the application of a data mining approach to
      describing and simulating farmers' decision rules in a catchment in northern
      Thailand. This approach is being applied to simulate social, economic and
      biophysical constraints on farmers' decisions in these areas as part of an
      integrated water management model.

PMID- 16289540
TI  - Photon correlation spectroscopy of brain mitochondrial populations: application
      to traumatic brain injury.
AB  - Mitochondrial dysfunction and pathology that contribute to a host of
      neurodegenerative diseases are deduced from changes in ultrastructure, routinely
      examined by a host of optical techniques. We adapted the technique of photon
      correlation spectroscopy (PCS) to evaluate calcium-induced structural alterations
      in isolated viable cortical and hippocampal mitochondria. In detecting calcium
      induced reductions in light intensity, PCS was more sensitive than absorbance
      across varying calcium concentrations. Mitochondrial populations encompass a
      broad distribution of sizes, confirmed by ultrastructural profiles, both which
      remain unaffected by calcium exposure. Cortical and hippocampal populations show
      fractional calcium-induced reductions in light scatter compared to subsequent
      maximal alamethicin-induced reductions. Although reductions in light scatter
      (refractive index) have been interpreted as mitochondrial swelling, PCS
      quantification of the mean mitochondrial radius demonstrates that mitochondrial
      size is unaffected by calcium exposure, but not alamethicin. Likewise, the
      population distribution histograms remain stable with calcium exposure, but shift
      to larger radii after alamethicin exposure. Furthermore, hippocampal
      mitochondrial populations from a neurodegenerative model of traumatic brain
      injury, lateral fluid percussion, demonstrate greater calcium-induced reductions
      in scatter intensity, which are associated with an initial population of large
      mitochondria becoming smaller. The disparate responses to calcium and subsequent
      alamethicin of mitochondria at 3 and 24 h after injury attest to an acute
      disruption of membrane permeability in mitochondria from injured brain. PCS
      provides quantitative indices of refractive index and size in isolated
      mitochondrial populations, aiding the evaluation of mitochondria in degenerative
      diseases.

PMID- 16289541
TI  - Clindamycin-resistance in methicillin-resistant Staphylococcus aureus isolated
      from animals.
AB  - Clindamycin is widely used in veterinary medicine to treat a variety of bacterial
      infections. Resistance to clindamycin amongst staphylococci may be due to
      modification of the ribosomal target site. Resistance due to this mechanism is
      encoded by the erm genes, which may be either constitutively or inducibly
      expressed. Inducible expression of resistance is not usually demonstrable by
      routine laboratory susceptibility testing, however, a relatively simple double
      disc agar diffusion test (D-test) may be used to detect the presence of inducible
      resistance. Two hundred and eighty-five isolates of methicillin-resistant
      Staphylococcus aureus (MRSA) isolated from infections in animals were tested
      using the D-test for the presence of inducible clindamycin resistance. One
      hundred and seven (71%) of the strains tested demonstrated inducible resistance
      to clindamycin, which were not detected on initial susceptibility testing. It has
      been shown that there is potential for staphylococci to develop resistance to
      clindamycin whilst on treatment when inducible resistance mechanisms are present.
      Therefore, routine screening for inducible resistance may be prudent.

PMID- 16289542
TI  - Quantification of porcine circovirus type 2 (PCV2) DNA in serum and tonsillar,
      nasal, tracheo-bronchial, urinary and faecal swabs of pigs with and without
      postweaning multisystemic wasting syndrome (PMWS).
AB  - The present study focused on PCV2 quantification by TaqMan PCR in nasal (n=99),
      tonsillar (n=108), tracheo-bronchial (n=72), urinary (n=91) and faecal (n=42)
      swabs, as well as in serum (n=57), from a total of 146 pigs received at the
      Pathological Diagnostic Service at the Veterinary School of Barcelona (Spain).
      Animals were classified into three categories based on histopathological and in
      situ hybridisation (ISH) results: PMWS affected pigs (Group A, n=42), PCV2
      subclinically infected pigs (Group B, n=29), and non-PMWS with PCV2 ISH negative
      pigs (Group C, n=75). Overall, tracheo-bronchial swabs had the higher PCV2 load
      followed by serum, tonsillar, nasal, faecal and, finally, urinary swabs. PCV2
      genome was also detected in different proportions in all three categories of
      pigs; in all tested sites, viral load means were significantly higher (P<or=0.02)
      in animals with PMWS (Group A pigs) than in animals without PMWS (Group B and C
      pigs). Therefore, the more severe the lesions, the higher amounts of viral genome
      by ISH, and the higher PCV2 load in serum and swab specimens. Except for the
      tracheo-bronchial swab, no significant differences (p>0.05) were observed among
      tested specimens when age-groups (pigs younger than 1.5 months, and equal or
      older than 1.5 months of age) were compared. In summary, PCV2 is presumably
      excreted through respiratory (nasal and tracheo-bronchial) and oral (tonsillar)
      secretions, urine and faeces of both PMWS and non-PMWS affected pigs, with higher
      viral loads being associated with the presence of PMWS lesions.

PMID- 16289544
TI  - Steinernema akhursti sp. n. (Nematoda: Steinernematidae) from Yunnan, China.
AB  - A new species of entomopathogenic nematode, herein described as Steinernema
      akhursti sp. n., was recovered from soil samples collected from Yunnan Province,
      the People's Republic of China. Both morphological and molecular data show
      congruently that S. akhursti sp. n. belongs to the Steinernema feltiae group. It
      can be separated from all described Steinernema species by the combined
      morphological and morphometrical characters of various stages of the nematodes.
      For the first generation male, the new species can be recognized by spicule
      length 90 +/- 4.6 microm, spicule tip blunt with an aperture on the ventral side,
      gubernaculum with a long and needle-shaped cuneus, and tail conoid with a
      prominent mucron on the tip and a concave on ventral side. For the infective
      juvenile, the combination of the following characters: body length 812 +/- 19
      microm, distance from anterior end to excretory pore 59 +/- 1.5 microm, tail
      length 73 +/- 2.9 microm, E% 77 +/- 4.5, lateral field with six evenly
      distributed and identical ridges at the middle body portion, and tail with long
      and slightly constrict hyaline portion can be used to separate the new species
      from other nematodes. For the female, the new species is characterized by: tail
      conoid with a short mucron and slightly swelling anal portion and a symmetrical,
      slightly protruding vulva with conspicuous double-flapped epiptygma. The nematode
      can be separated from other described species of Steinernema by DNA sequences of
      either a partial 28S rDNA or the internal transcribed spacer regions of rDNA and
      from the closely related species S. feltiae and Steinernema oregonense by cross
      breeding tests.

PMID- 16289545
TI  - New bioassay method to assess the pathogenicity of Colombian strains of
      Metarhizium anisopliae (Metsch.) Sorokin and Paecilomyces sp. (Deuteromycotina:
      Hyphomycetes) against the subterranean burrower bug Cyrtomenus bergi Froeschner
      (Hemiptera: Cydnidae).
AB  - Using a new sand bioassay method, the pathogenicity of three Colombian strains of
      Metarhizium anisopliae (i.e., CIAT 224, 245, and 230) and one strain of
      Paecilomyces sp. (CIAT 308) were tested against fourth instars of the
      subterranean burrower bug Cyrtomenus bergi Froeschner (Hem.: Cydnidae) in the
      laboratory. The proposed bioassay simulates the habitat of C. bergi and at the
      same time enables the evaluation of a large number of insects in a short period
      of time and under controlled conditions. All tested fungal species/strains were
      pathogenic against C. bergi. However, only low levels of mortality were obtained,
      and never exceeded 55%. In the screening experiment, M. anisopliae strains CIAT
      224 and CIAT 245 caused the highest levels of mortality. The use of the bioassay
      procedure described herein is discussed.

PMID- 16289543
TI  - Retron reverse transcriptase (rrtT) can be lost in multidrug resistant Salmonella
      enterica serovar Typhimurium DT 104 strains and influences virulence for mice.
AB  - In Salmonella enterica serovar Typhimurium, retron reverse transcriptase (rrtT),
      which is part of St 85 retron, is quite ubiquitous and is located in the thdF 
      yidY intergenic region. In this study, we showed that rrtT is relatively unstable
      in multidrug resistant, Salmonella genomic island 1 (SGI 1) positive strains. Out
      of 365 field strains, 55 were free of retron. In 54 of the rrtT negative strains,
      the excision must have occurred by the same mechanism in which the rrtT together
      with five other genes was excised. Altogether 8164 bp was missing in the
      chromosome of the rrtT negative strains. Since the deletion happened exactly
      between the right inverted repeat of IS 6100 and inside the yieE gene, we propose
      that intramolecular transposition of IS 6100 followed by homologous recombination
      was responsible for the excision. Excision of retron together with the right end
      of SGI 1 may also result in its stabilisation in the Salmonella typhimurium
      genome. Experimental deletion of rrtT resulted in an accelerated course of
      infection in orally infected mice. Since the retron excision occurred exclusively
      in multidrug resistant S. typhimurium, it cannot be excluded that such strains
      may increase their virulence in the future.

PMID- 16289546
TI  - Simultaneous detection of multiple mRNA markers CK19, CEA, c-Met, Her2/neu and
      hMAM with membrane array, an innovative technique with a great potential for
      breast cancer diagnosis.
AB  - The objective of this study was mainly to develop and evaluate a membrane array
      based method simultaneously detecting the expression levels of a multiple mRNA
      marker panel in the peripheral blood for used in complementary breast cancer
      diagnosis. The mRNA markers employed included cytokeratin 19 (CK-19),
      carcinoembryonic antigen (CEA), c-Met, Her2/neu, and mammaglobin (hMAM). The
      specimens of peripheral blood were collected from 80 healthy women and 102 female
      patients with breast cancer. The expression levels of molecular markers were
      evaluated by real-time Q-PCR and membrane array. Data obtained from real-time Q
      PCR and membrane array were subjected to linear regression analysis, revealing
      that there was a high degree of correlation between the results of these two
      methods (r=0.979, P<0.0001). The result of membrane array assay with a combined
      panel of five mRNA markers was demonstrated to achieve sensitivity of 80.6%, and
      specificity of 83.8% for breast cancer detection, much higher than those of
      analysis of single marker. In addition, we demonstrated that the membrane array
      method could detect circulating cancer cells at a density as low as five cancer
      cells per 1 ml of blood. The analysis of correlation between the outcome of
      membrane array and clinicopathological characteristics indicated that
      overexpression of the multiple marker panel was significantly correlated with
      tumor size (P=0.030) and TNM stage (0.009). In conclusion, the detection of
      circulating cancer cells by means of membrane array simultaneously monitoring
      five mRNA markers could significantly enhance the sensitivity and specificity for
      cancer cell detection.

PMID- 16289547
TI  - Transient information flow in a network of excitatory and inhibitory model
      neurons: role of noise and signal autocorrelation.
AB  - We investigate the performance of sparsely-connected networks of integrate-and
      fire neurons for ultra-short term information processing. We exploit the fact
      that the population activity of networks with balanced excitation and inhibition
      can switch from an oscillatory firing regime to a state of asynchronous irregular
      firing or quiescence depending on the rate of external background spikes. We find
      that in terms of information buffering the network performs best for a moderate,
      non-zero, amount of noise. Analogous to the phenomenon of stochastic resonance
      the performance decreases for higher and lower noise levels. The optimal amount
      of noise corresponds to the transition zone between a quiescent state and a
      regime of stochastic dynamics. This provides a potential explanation of the role
      of non-oscillatory population activity in a simplified model of cortical micro
      circuits.

PMID- 16289548
TI  - Self-regulation of local brain activity using real-time functional magnetic
      resonance imaging (fMRI).
AB  - Functional magnetic resonance imaging (fMRI) measures the blood oxygen level
      dependent (BOLD) signal related to neuronal activity. So far, this technique has
      been limited by time-consuming data analysis impeding on-line analysis. In
      particular, no brain-computer interface (BCI) was available which provided on
      line feedback to learn physiological self-regulation of the BOLD signal.
      Recently, studies have shown that fMRI feedback is feasible and facilitates
      voluntary control of brain activity. Here we review these studies to make the
      fMRI feedback methodology accessible to a broader scientific community such as
      researchers concerned with functional brain imaging and the neurobiology of
      learning. Methodological and conceptual limitations were substantially reduced by
      artefact control, sensitivity improvements, real-time algorithms, and adapted
      experimental designs. Physiological self-regulation of the local BOLD response is
      a new paradigm for cognitive neuroscience to study brain plasticity and the
      functional relevance of regulated brain areas by modification of behaviour.
      Voluntary control of abnormal activity in circumscribed brain areas may even be
      applied as psychophysiological treatment.

PMID- 16289549
TI  - Competitive spiking and indirect entropy minimization of rate code: efficient
      search for hidden components.
AB  - Our motivation, which originates from the psychological and physiological
      evidences of component-based representations in the brain, is to find neural
      methods that can efficiently search for structures. Here, an architecture made of
      coupled parallel working reconstruction subnetworks is presented. Each subnetwork
      utilizes non-negativity constraint on the generative weights and on the internal
      representation. 'Spikes' are generated within subnetworks via winner take all
      mechanism. Memory components are modified in order to directly minimize the
      reconstruction error and to indirectly minimize the entropy of the spike rate
      distribution, via a combination of a stochastic gradient search and a novel
      tuning method. This tuning dynamically changes the learning rate: the higher the
      entropy of the spike rate, the higher the learning rate of the gradient search in
      the subnetworks. This method effectively reduces the search space and increases
      the escape probability from high entropy local minima. We demonstrate that one
      subnetwork can develop localized and oriented components. Coupled networks can
      discover and sort components into the subnetworks; a problem subject to
      combinatorial explosion. Synergy between spike code and rate code is discussed.

PMID- 16289550
TI  - Inferring network activity from synaptic noise.
AB  - During intense network activity in vivo, cortical neurons are in a high
      conductance state, in which the membrane potential (V(m)) is subject to a
      tremendous fluctuating activity. Clearly, this "synaptic noise" contains
      information about the activity of the network, but there are presently no methods
      available to extract this information. We focus here on this problem from a
      computational neuroscience perspective, with the aim of drawing methods to
      analyze experimental data. We start from models of cortical neurons, in which
      high-conductance states stem from the random release of thousands of excitatory
      and inhibitory synapses. This highly complex system can be simplified by using
      global synaptic conductances described by effective stochastic processes. The
      advantage of this approach is that one can derive analytically a number of
      properties from the statistics of resulting V(m) fluctuations. For example, the
      global excitatory and inhibitory conductances can be extracted from synaptic
      noise, and can be related to the mean activity of presynaptic neurons. We show
      here that extracting the variances of excitatory and inhibitory synaptic
      conductances can provide estimates of the mean temporal correlation-or level of
      synchrony-among thousands of neurons in the network. Thus, "probing the network"
      through intracellular V(m) activity is possible and constitutes a promising
      approach, but it will require a continuous effort combining theory, computational
      models and intracellular physiology.

PMID- 16289551
TI  - Zinc Finger Protein 202: a new candidate gene for ischemic heart disease: The
      Copenhagen City Heart Study.
AB  - OBJECTIVE: Zinc Finger Protein 202 (ZNF202) is a transcriptional repressor of
      genes affecting the vascular endothelium as well as lipid metabolism. A phenotype
      associated with genetic variation in ZNF202 is presently unknown. We tested the
      hypothesis that a common variant in ZNF202, A154V, predicts risk of ischemic
      heart disease (IHD), myocardial infarction (MI), and ischemic cerebrovascular
      disease (ICVD). METHODS AND RESULTS: We conducted a prospective study of more
      than 9000 individuals from the general population with 24 years follow-up. In
      women, age-adjusted hazard ratios in heterozygotes and homozygotes versus non
      carriers were 1.2 (95% CI: 1.0-1.5, P = 0.04) and 1.5 (1.1-2.1, P = 0.007) for
      IHD, 1.5 (1.1-2.1; P = 0.01) and 1.7 (1.1-2.8, P = 0.02) for MI, and 1.3 (1.0
      1.8, P = 0.07) and 1.3 (0.8-2.1; P = 0.33) for ICVD. Adjustments for lipids and
      lipoproteins did not alter these hazard ratios substantially. Genotype did not
      predict risk in men. Finally, results for IHD were borderline significant (P =
      0.06) in an independent case-control study including 933 patients and 8068
      controls. CONCLUSION: This is the first study to suggest that ZNF202 could be a
      new candidate gene for IHD and MI in the general population.

PMID- 16289552
TI  - Chronic tics and Tourette syndrome in patients with obsessive-compulsive
      disorder.
AB  - Tourette syndrome (TS) and chronic motor/vocal tics (CMVT) are both common
      disorders in patients with obsessive compulsive disorder (OCD). However, there
      have been few studies evaluating the differences between the OCD with TS and OCD
      with CMVT subgroups. This study was conducted in order to further investigate
      possible differences between the expression of the OCD phenotype in OCD with TS
      and that seen in OCD with CMVT. One hundred and fifty-nine outpatients referred
      to an OCD research program were evaluated using the following instruments: the
      Structured Clinical Interview for DSM-IV; the Yale-Brown Obsessive Compulsive
      Scale; the Yale Global Tic Severity Scale; and the USP-HARVARD Repetitive
      Behaviors Interview. Patients were divided into three groups: OCD patients
      without tics (OCD-TICS, n=98), OCD patients with chronic motor or vocal tics
      (OCD+CMVT, n=31) and OCD patients with TS (OCD+TS, n=30). OCD+CMVT patients were
      similar to OCD+TS patients regarding the frequency of intrusive sounds, repeating
      behaviors, counting and tic-like compulsions (in both cases more frequent than in
      OCD-TICS patients). For age at obsessive-compulsive (OC) symptom onset, sensory
      phenomena score, number of comorbidities, frequency of somatic obsessions, bodily
      sensations and just-right perceptions, OCD+CMVT patients tended to be in between
      the other two groups. Our results suggest that there are qualitative and
      quantitative differences in the phenotypic expression of tic disorders in OCD
      patients, depending on whether the subject has TS or only CMVT.

PMID- 16289554
TI  - Characteristics of captive Japanese black bears (Ursus thibetanus japonicus)
      semen collected by electroejaculation with different voltages for stimulation and
      frozen-thawed under different conditions.
AB  - The Japanese black bear (Ursus thibetanus japonicus) is an endangered species in
      some areas of Japan, and semen collection and cryopreservation are important
      means to preserve genetic resources and prevent extinction. The aim of the
      present study was to improve the methods for electroejaculation and
      cryopreservation in these bears. We collected the semen from captive mature
      Japanese black bears during the mating season by the electroejaculation method
      using maximum stimulus voltages of 10 V (n=9) and 7 V (n=15), and compared the
      characteristics of fresh semen after collection. None of the variables examined
      (i.e. total sperm count, motility, viability, morphology, and rate of urine
      contamination) were statistically different between the two electro-stimulus
      voltages. After the semen obtained was cryopreserved, the effects of three
      different diluents (egg yolk-TRIS-citrate-glucose, egg yolk-TRIS-citrate
      fructose, and egg yolk-TRIS-citrate-fructose-lactose-raffinose; n=10) and two
      different incubation times (1-1 and 3-0 h of cooling-glycerol equilibration
      times; n=12) on frozen-thawed spermatozoa. None of the variables examined (i.e.
      motility, viability and morphology) were statistically different among the three
      diluents and between the two incubation times. The results indicate that, in the
      collection and cryopreservation of Japanese black bear semen: (1) a maximum
      voltage of 7 V may be enough to obtain ejaculates; (2) the three diluents
      examined were useful; and (3) glycerol equilibration time may be omitted with
      prior cooling for 3h.

PMID- 16289553
TI  - Quality and freezing qualities of first and second ejaculates collected from
      endangered Gulf Coast Native rams.
AB  - The Gulf Coast Native sheep, or Louisiana Native sheep, is an endangered
      previously feral domestic sheep population of European origin that has been under
      natural selection pressure for reproductive survival in their transplanted range
      while roaming in the southern Gulf Coast Region of the United States. This sheep
      population has an increased natural resistance to internal parasites, breeds year
      around and has a greater percentage of live lambs as compared with other breeds
      of sheep raised in similar environments. To preserve the genetic diversity of
      this important feral sheep population, semen was collected by electro-ejaculation
      and subjected to cryopreservation for subsequent storage in a genome resource
      bank. Unrelated rams (n=5) were collected 3 days-a-week, allowing at least 2 days
      of rest between collections. Two ejaculates were obtained from each ram per
      collection day, with the second collection conducted 10min after the first
      ejaculation. Semen was processed using the standard Salamon cryopreservation
      procedure in a Tris-yolk-glycerol extender, frozen in 0.5ml plastic straws using
      liquid nitrogen (LN(2)) vapor and stored in LN(2). Each ejaculate was evaluated
      for volume, sperm concentration/ml (x10(9)/ml), number of spermatozoa/ejaculate
      (x10(9)), sperm progressive motility (%) for pre-cooled semen, cooled semen and
      semen after thawing. For the five rams, each semen variable for the first
      ejaculate was compared with that of the second ejaculate collected 10min later.
      The mean semen volume, sperm concentration and number of spermatozoa per
      ejaculate obtained from the first ejaculate were significantly greater (P< or
      =0.01) than those of the second ejaculate (comparisons being 1.62 and 1.06; 3.2
      and 1.5; 5.4 and 1.8, respectively). Overall, the mean motility of pre-cooled (22
      degrees Celsius), cooled (5 degrees Celsius) and frozen (-196 degrees Celsius)
      post-thawed spermatozoa was less (P< or =0.01) in the first ejaculate (71.5, 64.8
      and 34.1%, respectively) compared with that of the second ejaculate (75, 72.4 and
      44.1%, respectively). Conversely, no differences were detected in loss in the
      percent progressive motility of sperm from cooled sperm to post-thaw sperm from
      the first and second ejaculates. In summary, our findings suggest sperm collected
      during the second ejaculate 10min after the first ejaculate of rams survives
      thawing with a greater rate of progressive motility than that of the first
      ejaculate. The ability to collect two consecutive ejaculates in a short period by
      electro-ejaculation could be valuable for gamete resource banking and preserving
      genetic diversity of the Gulf Coast Native sheep.

PMID- 16289555
TI  - Complement activation after lumbosacral ventral root avulsion injury.
AB  - A lumbosacral ventral root avulsion (VRA) injury results in a pronounced loss of
      motoneurons, in part due to apoptosis. Caspase inhibitors may rescue motoneurons
      after a VRA in neonatal rats, but this treatment approach has been unsuccessful
      to protect motoneurons subjected to the same injury in adult rats. Other
      mechanisms may contribute to the retrograde motoneuron death encountered in adult
      animals. Here, we study whether the complement system, a part of the innate
      immune system, contributes to motoneuron death after a lumbosacral VRA. Adult
      Sprague-Dawley rats underwent a unilateral L5-S2 VRA injury. At 10 days
      postoperatively, quantitative immunohistochemical studies demonstrated that the
      lytic membrane attack complex (MAC) targeted approximately 38% of axotomized
      motoneurons. The MAC inhibitor Clusterin was concurrently expressed at
      significantly higher levels in astrocytes and de novo in 30% of the remaining
      motoneurons. Our data suggest that complement activation and necrosis contribute
      to motoneuron death after lumbosacral VRA injuries. We speculate that inhibition
      of MAC may constitute a potential neuroprotective strategy following cauda equina
      injuries.

PMID- 16289557
TI  - Increased oxidative stress in patients with chronic obstructive pulmonary disease
      (COPD) as measured by redox status of plasma coenzyme Q10.
AB  - STUDY OBJECTIVES: The percentage of oxidized coenzyme Q10 in total coenzyme Q10
      (%CoQ-10) has been shown to indicate the degree of systemic oxidative stress.
      Chronic obstructive pulmonary disease (COPD) is regarded as a systemic disease
      that is linked to oxidative stress in its pathogenesis. In this study, the plasma
      %CoQ-10 levels in COPD patients were determined and assessed. In addition, the
      effect of oxygen supplementation on plasma %CoQ-10 was also evaluated. MATERIAL
      AND METHODS: Thirteen COPD patients who had not received oxygen supplementation
      (COPD-Pt), five COPD patients who had received oxygen supplementation (COPD + O2)
      and 20 age-matched control subjects (CONTROL) were enrolled. We have also
      enrolled 83 young healthy non/slight smokers (smoking index <20 pack-year) and 24
      young healthy smokers (smoking index > or = 20 pack-year) in order to assess the
      effect of smoking history on %CoQ-10 level. Their plasma was collected and plasma
      %CoQ-10 levels were determined and compared. RESULTS AND CONCLUSION: The plasma
      %CoQ-10 of COPD-Pt was 6.3 +/- 2.3, significantly higher than that of CONTROL,
      4.7 +/- 1.6 (p < 0.05), indicating an increased oxidative stress in the patients.
      In contrast, no significant difference in %CoQ-10 was observed between young
      healthy non/slight smokers (%CoQ-10 = 3.2 +/- 0.9) and young healthy smokers
      (%CoQ-10 = 3.7 +/- 1.3). Our observation of five COPD patients who received an
      oxygen supplementation revealed that their %CoQ-10 values (4.0 +/- 1.5) were
      significantly lower than those in COPD-Pt subjects (p < 0.05), suggesting that
      oxygen supplementation ameliorates the oxidative stress. In contrast, our study
      showed that no significant difference was observed among the three groups in
      plasma levels of Vitamin C or E. In conclusion, plasma %CoQ-10 levels are
      increased in COPD patients and oxygen supplementation attenuates this increasing
      effect by COPD. This implies that %CoQ-10 might be used practically to assess the
      COPD patients systemically.

PMID- 16289558
TI  - Antireflux surgery and esophageal mucosal DNA damage.
AB  - Gastroesophageal reflux disease (GERD) is characterized by reflux of
      gastroduodenal contents, esophagitis and oxidative tissue damage in the distal
      esophagus. It may ultimately lead to the development of a pre-malignant Barrett's
      esophagus and subsequently to carcinoma. Antireflux surgery is an effective
      therapeutic tool to relieve GERD symptoms and to normalize the reflux to the
      distal esophagus. However, antireflux surgery may be insufficient to restore
      oxidative insult, which can promote DNA adduct formation and subsequent
      initiation of carcinogenesis. Controversy exists whether antireflux surgery can
      reverse the development of carcinoma in the mucosa. We aimed to test the effect
      of antireflux surgery on DNA adduct formation in the esophagus. Patients (n = 19)
      with objectively confirmed GERD underwent antireflux surgery and were followed up
      for 6 months after which a symptom evaluation, control endoscopy, biopsy and pH
      measurements were performed. The amounts of DNA adducts in the proximal and
      distal mucosa of the esophagus were measured using the 32-P-postlabelling method.
      After the surgery, esophageal acid exposure was normalized in all the patients
      and symptoms were relieved in all but one patient. Endoscopic examinations showed
      that erosive esophagitis had healed in all the cases 6 months after the surgery.
      Barrett's esophagus was found in six cases in preoperative biopsies. The amount
      of DNA adducts in the distal esophagus was higher than in the proximal esophagus
      both pre- and postoperatively. Antireflux surgery did not change this pattern and
      was thus not capable of reducing DNA adduct formation. The level of DNA damage
      was similar in the patients having Barrett's esophagus compared to the rest of
      the patients. Antireflux surgery is insufficient to normalize DNA damage due to
      GERD. Our observations suggest that antireflux surgery is perhaps not effective
      in the prevention of carcinogenesis because of the persisting DNA damage.

PMID- 16289556
TI  - Dorsal raphe nucleus and locus coeruleus neural networks and the elaboration of
      the sweet-substance-induced antinociception.
AB  - In order to investigate the effects of monoaminergic neurons of the dorsal raphe
      nucleus (DRN) and locus coeruleus (LC) on the elaboration and control of sweet
      substance-induced antinociception, male albino Wistar rats weighing 180-200 g
      received sucrose solution (250 g/L) for 7-14 days as their only source of liquid.
      After the chronic consumption of sucrose solution, each animal was pretreated
      with unilateral microinjection of ibotenic acid (1.0 microg/0.2 microL) in the
      DRN or in the LC. The tail withdrawal latencies of the rats in the tail-flick
      test were measured immediately before and 7 days after this treatment. The
      neurochemical lesion of locus coeruleus, but not of DRN neural networks with
      ibotenic acid, after the chronic intake of sweetened solution, decreased the
      sweet-substance-induced antinociception. These results indicate the involvement
      of noradrenaline-containing neurons of the LC in the sucrose-induced
      antinociception. We also consider the possibility of DRN serotonergic neurons
      exerting some inhibitory effect on the LC neural networks involved with the
      elaboration of the sweet-substance-induced antinociception.

PMID- 16289559
TI  - A chromatographic estimate of the degree of surface heterogeneity of reversed
      phase liquid chromatography packing materials. II-Endcapped monomeric C18-bonded
      stationary phase.
AB  - In a previous report, the heterogeneity of a non-endcapped C30-bonded stationary
      phase was investigated, based on the results of the measurements of the
      adsorption isotherms of two neutral compounds (phenol and caffeine) and two
      ionizable compounds (sodium naphthalene sulfonate and propranololium chloride) by
      frontal analysis (FA). The same method is applied here for the characterization
      of the surface heterogeneity of two new brands of endcapped C18-bonded stationary
      phases (Gemini and Sunfire). The adsorption isotherms of the same four chemicals
      were measured by FA and the results confirmed by the independent calculation of
      the adsorption energy distribution (AED), using the expectation-maximization (EM)
      method. The effect of the length of the bonded alkyl chain was investigated.
      Shorter alkyl-bonded-chains (C18 versus C30) and the end-capping of the silica
      surface contribute to decrease the surface heterogeneity under the same
      experimental conditions (30% methanol, 25 mM NaCl). The AEDs of phenol and
      caffeine are bimodal with the C18-bonded columns while they are trimodal and
      quadrimodal, respectively, with a non-endcapped C30-bonded column. The
      "supersites" (adsorption energy > 20 kJ/mol) found on the C30-Prontosil column
      and attributed to a cation exchange mechanism completely disappear on the C18
      Gemini and C18-Sunfire, probably because the end-capping of the silica surface
      eliminates most if not all the ionic interactions.

PMID- 16289561
TI  - Aqueous extract of black tea (Camellia sinensis) prevents ethanol+cholecystokinin
      induced pancreatitis in a rat model.
AB  - Black Tea Extract (BTE), a phytocompound has been attributed with a plethora of
      health-promoting actions. We have previously demonstrated that BTE inhibits
      chronic hepatitis in a rat model induced with high-fat and ethanol (EtOH). This
      study reports that BTE prevents altered pancreatic acinar cell functions,
      oxidative stress, inflammatory changes and DNA damage in the EtOH+cholecystokinin
      (CCK)-induced model of pancreatitis. The EtOH+CCK model rats were administered
      with BTE, and were examined the activity of pancreatic digestive enzymes (amylase
      and lipase), proinflammatory cytokines (IL-6 and TNF-alpha), oxidative and
      antioxidative enzymes (nitric oxide, NO; malondialdehyde, MDA; superoxide
      dismutase, SOD; catalase, CAT), antioxidant level (glutathione, GSH),
      histopathological changes and the integrity of genomic DNA. Results show that
      because of chronic EtOH treatment, serum level of amylase and lipase (two
      biomarkers for pancreatitis) and pancreatic levels of MDA and NO (two biomarkers
      of oxidative stress) increased significantly, which could be effectively blunted
      by BTE. BTE could normalize EtOH+CCK-induced suppressed activities of SOD and
      CAT, and GSH content of pancreatic tissue. Also, histopathological and
      inflammatory changes during EtOH+CCK-induced pancreatitis could be blunted by
      BTE. Furthermore, BTE could effectively reduce EtOH+CCK-induced increase in DNA
      fragmentation and damage. These findings suggest that BTE prevents pancreatitis
      caused by chronic EtOH+CCK toxicity presumably by enhancing antioxidant, anti
      inflammatory and antiapoptotic activity in rats.

PMID- 16289560
TI  - Improving glycogenesis in Streptozocin (STZ) diabetic mice after administration
      of green algae Chlorella.
AB  - Chlorella, a type of unicellular fresh water algae, has been a popular foodstuff
      in Japan and Taiwan. Studies have shown the hypoglycemic effects of Chlorella in
      alloxan-induced and Streptozocin (STZ)-induced diabetic animals. However, the
      mechanisms by which Chlorella treatment affects blood glucose homeostasis have
      not been studied. Diabetes in ICR mice was induced by injection of STZ.
      Lipogenesis in vivo was measured by incorporating 3H-H2O into lipids in brown and
      white adipose tissues. Glucose uptake in the liver and soleus muscles was
      measured by assaying 2-deoxy-D-[1,2-3H] glucose levels. The effects of Chlorella
      on serum non-esterified fatty acids (NEFA) were measured with commercial assay
      kits. Insulin-stimulated lipogenic rates in brown and white adipose tissues were
      unaffected by Chlorella. However, Chlorella increased 2-deoxyglucose uptake in
      the livers and soleus muscles in normal and STZ mice compared to that in their
      respective controls (p < 0.01). In addition, fasting NEFA levels were lower in
      Chlorella-treated STZ mice compared to H2O-treated STZ mice (p < 0.005). The
      current results suggest that the hypoglycemic effects of Chlorella are due to an
      enhancement of glucose uptake in the liver and in soleus muscles. The improved
      insulin sensitivity after Chlorella treatment could be also due to lower NEFA
      levels, since insulin sensitivity is usually blunted by elevated NEFA in
      diabetes.

PMID- 16289562
TI  - Modulation of glucose transporter (GLUT4) by vanadate and Trigonella in alloxan
      diabetic rats.
AB  - Oral administration of vanadate is an effective treatment for diabetes in animal
      models. However, vanadate exerts these effects at high doses and several toxic
      effects are produced. Low doses of vanadate are relatively safe but are unable to
      elicit any antidiabetic effect. The present study explored the prospect of using
      low doses of vanadate in combination with Trigonella seed powder (TSP) to
      evaluate their antidiabetic effect in alloxan-diabetic rats. Alloxan-diabetic
      rats were treated with insulin, vanadate, TSP and vanadate and TSP in combination
      for 3 weeks. The effect of these antidiabetic compounds was examined on general
      physiological parameters and distribution of glucose transporter (GLUT4) in
      skeletal muscle by immunoblotting and immunohistochemistry. Treatment of alloxan
      diabetic rats with insulin, vanadate, TSP and vanadate in combination with TSP
      revived normoglycemia and restored the disturbances in the distribution of GLUT4
      in skeletal muscle. TSP treatment was only partially effective in the restoration
      of diabetic alterations. The treatment of diabetic rats with combined doses of
      vanadate and TSP was most effective in the normalization of plasma glucose levels
      and correction of altered GLUT4 distribution.

PMID- 16289564
TI  - Tracing the emergence of drug-resistance in coccidia (Eimeria spp.) of commercial
      broiler flocks medicated with decoquinate for the first time in the United
      Kingdom.
AB  - Decoquinate is a quinolone coccidiostat introduced during 1967 as an in-feed
      prophylactic for broiler chickens. Despite early drug-resistance problems and its
      age, the drug is still used commercially worldwide. Decoquinate here serves as a
      valuable model in a field study that addresses the dynamics and economic impact
      of the development of coccidial resistance to potent synthetic anticoccidial
      drugs. The results of this unique, hitherto unpublished, study on the initial
      emergence of resistance of avian coccidia (Eimeria spp.) to a new drug in the
      field may be of strategic value in the continued use of decoquinate or the
      introduction of new drugs. The commercial performance of the first 3-5 crops of
      broilers to be medicated with decoquinate on each of six farms was monitored
      during 14 months in 1968-1969, supplemented by assessments of the species,
      population dynamics and decoquinate-resistance of coccidia isolated from each
      farm. During the rearing of each flock in a single shed on each farm, oocysts
      were counted in fresh faecal samples collected on three occasions, and the
      species were identified by their morphology if possible, supported if necessary
      by the biological characteristics of infections in chickens. E. acervulina was
      the most common species, followed by E. mitis, E. maxima, E. tenella and E.
      praecox. E. brunetti occurred rarely, and E. necatrix was not found. Decoquinate
      resistance was evident in several species during the rearing of the first
      decoquinate-medicated crop on each farm, although clinical coccidiosis did not
      occur. It was concluded that inherently resistant mutants of E. acervulina, E.
      brunetti, E. maxima, E. tenella, and probably also E. mitis and E. praecox, were
      selected from field populations by 6 weeks during their first exposure to
      decoquinate. During up to four more subsequent crops, cycling of resistant
      parasites stimulated host immunity, which had no obvious adverse impact on
      commercial performance. There was no apparent seasonal effect. A hypothesis is
      proposed to explain the sudden and rapid emergence of quinolone-resistance in the
      coccidia, and why bird health was not thereby compromised in these circumstances.

PMID- 16289563
TI  - Secretory leukocyte protease inhibitor levels in cervicovaginal secretion of
      elderly women.
AB  - OBJECTIVE: Secretory leukocyte protease inhibitor (SLPI) is a potent inhibitor of
      human leukocyte elastase. The aim of the present study was to examine whether
      there is an association between the SLPI concentration in the cervicovaginal
      secretion (CS) and vaginal complaints of post-menopausal women. METHODS: Uterine
      cervix tissues and CS of peri- or post-menopausal women were obtained. SLPI was
      assayed by ELISA. To determine the level of SLPI mRNA and the localization of
      SLPI protein in the uterine cervix, we performed RT-PCR and immunochemical
      staining, respectively. RESULTS: The levels of SLPI in the CS of post-menopausal
      women with vaginal complaints were significantly lower that those of post
      menopausal women without vaginal complaints. The levels of SLPI in the CS of post
      menopausal women were lower that those of peri-menopausal women and post
      menopausal women treated with hormone replacement therapy. Positive staining was
      observed in epithelial cells of the cervix of elderly women, however, the
      intensity was weaker than that in peri-menopausal women. Positive staining was
      also observed in gland cells of the cervix of peri-menopausal women, but not in
      those of post-menopausal women. SLPI transcripts were detected in the cervix of
      post-menopausal women. The treatment of post-menopausal women with vaginal
      estrogen increased the concentrations of SLPI in CS of post-menopausal women.
      CONCLUSIONS: The present findings suggest that the decreased amount of SLPI in
      the CS of post-menopausal women might be one of the causes of the symptoms of
      post-menopausal women and contribute to the immunodefense mechanisms of the
      elderly women.

PMID- 16289565
TI  - Potential existence of a sylvatic cycle of Taenia ovis krabbei in Patagonia,
      Argentina.
AB  - Red deer (Cervus elaphus) were introduced in southern Latin America about a
      century ago and characteristics of the invasion raise concerns over their
      epidemiological role for various diseases. We report on the possible occurrence
      of Taenia ovis krabbei established in a sylvatic cycle in Patagonia. Hook
      characters, size, appearance, and location of a cysticercus from a wild red deer
      are consistent with Taenia ovis ovis or T. o. krabbei. Although it is not
      possible to differentiate between T. o. ovis and T. o. krabbei on morphological
      grounds with certainty, several biological characteristics indicate the
      cysticercus may belong to T. o. krabbei. Red deer have been reported to be
      refractory to T. o. ovis infection whereas other potential intermediate hosts
      like cattle, goats, pigs and sheep have been shown to be refractory to T. o.
      krabbei. Other native ungulates sympatric with red deer in Patagonia include Lama
      guanicoe and the endangered huemul deer (Hippocamelus bisulcus). Possible or
      known definitive hosts include native felids like Puma concolor, Felis colocolo,
      F. guigna and canids like Dusicyon griseus, D. culpaeus, and domestic dogs.

PMID- 16289566
TI  - Discrimination between six species of canine microfilariae by a single polymerase
      chain reaction.
AB  - Canine dirofilariasis caused by Dirofilaria immitis is usually diagnosed by
      specific antigen testing and/or identification of microfilariae. However, D.
      immitis and at least six other filariae can produce canine microfilaremias with
      negative heartworm antigen tests. Discriminating these can be of clinical
      importance. To resolve discordant diagnoses by two diagnostic laboratories in an
      antigen-negative, microfilaremic dog recently imported into the US from Europe we
      developed a simple molecular method of identifying different microfilariae, and
      subsequently validated our method against six different filariae known to infect
      dogs by amplifying ribosomal DNA spacer sequences by polymerase chain reaction
      using common and species-specific primers, and sequencing the products to confirm
      the genotype of the filariae. We identified the filaria in this dog as D. repens.
      This is the first case of D. repens infection in the United States. Additionally,
      we examined microfilariae from five additional antigen-negative, microfilaremic
      dogs and successfully identified the infecting parasite in each case. Our
      diagnoses differed from the initial morphological diagnosis in three of these
      cases, demonstrating the inaccuracy of morphological diagnosis. In each case,
      microfilariae identified morphologically as A. reconditum were identified as D.
      immitis by molecular methods. Finally, we demonstrated that our PCR method should
      amplify DNA from at least two additional filariae (Onchocerca and Mansonella),
      suggesting that this method may be suitable for genotyping all members of the
      family Onchocercidae.

PMID- 16289567
TI  - Comparison of different methods for the solubilisation of Neospora caninum
      (Phylum Apicomplexa) antigen.
AB  - Parasite antigens are of interest both for the development of better diagnostic
      tools and potential subunit vaccines. Particularly, relevant in this regard are
      membrane proteins as the first point of contact between host and parasite. Here,
      four different methods for the extraction and solubilisation of Neospora caninum
      proteins were evaluated by comparing protein yield, specific antigenicity and
      relative protein abundance in the electrophoresis profile. Extraction with SDS
      and sulphobetaines (SB) gave higher yields than those achieved using the standard
      sonication method. SDS and SB preparations also gave the best signal to noise
      ratio when used as capture antigens in an ELISA. Electrophoresis of the three
      preparations showed an even protein-banding pattern spread out over the 90-10 kDa
      size range. However, there were a greater proportion of lower molecular weight
      proteins when the sonication method was used suggesting that this method may have
      resulted in the degradation/proteolysis of some proteins. Extraction with Triton
      X-114 resulted in the concentration of three or four proteins but led to a
      considerable reduction in the overall protein yield. The ELISA indicated that not
      all of the Triton X-114 extracted proteins were involved in specific antibody
      binding. The optimal extraction method for parasite proteins depends on the
      intended application.

PMID- 16289568
TI  - Vitellogenin polypeptide levels in one susceptible and one cadmium-resistant
      strain of Oncopeltus fasciatus (Heteroptera: Lygaeidae), and its role in cadmium
      resistance.
AB  - The heavy metal Cd has recently been shown to have endocrine disrupting activity
      in different vertebrate species. In the insect Oncopeltus fasciatus, Cd exposure
      delays ovarian maturation and inhibits vitellogenesis, probably through a
      reduction in vitellogenin (Vg) polypeptide synthesis. An O. fasciatus strain was
      selected in the laboratory for Cd resistance with gradually increasing Cd
      concentrations for 50 generations. Cd-selected (OCdR) insects were 2.7-2.3 times
      more resistant to chronic exposure to Cd than susceptible (OS) insects. OCdR
      females showed increased (up to 90%) Vg polypeptide levels in hemolymph. Vg
      polypeptide synthesis was equally decreased in OCdR and OS females after acute Cd
      exposure, indicating that resistance in the OCdR strain was not due to a reduced
      sensitivity of the target of Cd. Vg polypeptide concentrations and ovarian
      maturation in acutely exposed OCdR females, however, were equal to those of
      control OS females. OCdR females chronically exposed to Cd showed a 30% decrease
      in Vg polypeptide concentrations, relative to control OS females. It is concluded
      that increased Vg polypeptide levels play an important role in resistance to the
      toxic effects of Cd on reproduction in the OCdR strain, and that this novel Cd
      resistance mechanism has the potential to evolve in vertebrate species in which
      Cd inhibits Vg synthesis by disruption of the endocrine system.

PMID- 16289569
TI  - Chirp rate is independent of male condition in a synchronising bushcricket.
AB  - Males of the bushcricket Mecopoda elongata synchronise their chirps with
      neighbouring males, but because synchrony is imperfect, one male's chirp preceeds
      the other by some 50-200 ms. Since a male's intrinsic chirp rate is critical for
      the establishment of the leader role in a duet, and females prefer the leader in
      a choice situation, we investigated a possible condition dependence of this male
      trait. In a duet leader males are usually those calling at a higher intrinsic
      rate; therefore, we investigated whether calling at a higher rate indicates male
      condition. The calling metabolism was quantified in a respirometer; the factorial
      slope of males calling at a high rate was three times higher compared to males
      calling at lower rates. Males produce on average 3.4 singing bouts/per night, and
      there is a significant increase in chirp periods (CPs) with successive singing
      bouts. Call properties were investigated throughout a male's life; chirp period
      increases significantly with age. Two groups of males were reared on either a low
      or a high-nutrition diet, and the influence of male condition on different song
      parameters was investigated. CPs in two feeding regimes did not differ
      significantly, although males of the low-nutrition diet group were significantly
      affected by nutrition with respect to mortality, a delayed last moult and reduced
      weight as adults. We therefore conclude that solo chirp rates do not reflect
      phenotypic male condition properly.

PMID- 16289570
TI  - [A case of acute gastric volvulus in a child].
AB  - Gastric volvulus is an abnormal rotation of the stomach around its axis. The
      acute form is a surgical emergency, which doesn't tolerate any therapeutic delay.
      We report on a case in a young girl, revealed by painful epigastric mass and
      distended gastric bubble on abdominal X-ray. This case was been successfully
      treated by detorsion and gastropexy. The clinical picture of gastric volvulus is
      characterised by the Borchardt triad of symptoms: upper abdominal pain, vomiting
      and difficulty to pass a nasogastric tube. The gastrointestinal barium series and
      CT-scan help to confirm the diagnosis. As was demonstrated in this case, the
      treatment is surgical by reducing the volvulus and fixing the stomach to prevent
      recurrence.

PMID- 16289571
TI  - Spatial and temporal changes in benthic communities of the Galician continental
      shelf after the Prestige oil spill.
AB  - Two years after the Prestige oil spill (POS) an assessment of the effects on
      benthic fauna was carried out using the data obtained in five multidisciplinary
      surveys. Otter trawl, beam trawl, suprabenthic sled and box corer were used to
      study the main benthic compartments, along eight transects perpendicular to the
      coastline. Beam trawl was also employed to quantify the amount of tar aggregates
      on the continental shelf. No significant correlations between tar aggregates and
      species richness, biomass and diversity of benthic communities were found. This
      result was corroborated when the role of depth, season, latitude and sediment
      characteristics was examined by canonical ordination, in which POS-related
      variables had low influence on spatial distribution patterns. Depth and sediment
      grain diameter profoundly influence epibenthic communities. Sediment organic
      content is a third key variable for the infaunal, suprabenthic and lower-sized
      epibenthic communities, but not for the larger epibenthic communities.
      Nevertheless, a decrease in the densities of several epibenthic indicators was
      detected the first year after spill, followed by a noteworthy recovery in 2004.
      Non-macroscopic toxicity and some oceanographic agents are suggested as possible
      causes of these shifts.

PMID- 16289572
TI  - Structural and functional response of meiofauna rocky assemblages to sewage
      pollution.
AB  - Despite meiofauna being one of the most popular tool for detecting the ecological
      effects of different sources of impact, the application of structured
      experimental designs to this benthic component is typically neglected, especially
      in subtidal rocky shores. In this study, an asymmetrical design was used to
      detect hard-bottom meiofaunal abundance and biodiversity response to sewage
      discharge. Sampling was carried out at a depth of 3-4 m by SCUBA diving, by means
      of a modified manual corer. Six replicate cores were collected at three sites (80
      100 m apart), at each of three locations (one purportedly impacted [I] and two
      controls [Cs]). A total of 84,994 specimens were collected. The outfall affected
      meiofaunal assemblages in terms of taxon richness, by determining a significant
      reduction of the number of taxa in the disturbed location, and community
      structure, by causing functional changes in terms of a decrease of the abundance
      of nematodes and an increase of the hydrozoan component. Nematodes and syllid
      polychaetes showed significant lower average abundance at I. Multivariate
      analyses showed that both meiofaunal assemblage and syllids were significantly
      different at I compared with Cs. The sewage outfall also affected patterns of
      spatial distribution at the scale of site (100 m apart) and of replicate units
      (centimetres apart), both in syllids and in nematodes. Our results provide
      evidence that the selection of multiple controls is crucial to prevent the
      widespread risk of Type II error, highlighting the need of more accurate
      experimental designs when dealing with meiofauna.

PMID- 16289573
TI  - Surface treatment: a potential approach for enhancement of solid-state
      photostability.
AB  - The potentials of a simple surface treatment technique aiming at modifying solid
      state properties with emphasis on photostability were investigated using
      methyldopa (MD), a photosensitive drug substance. MD was treated with a
      preselected solvent by stirring a drug suspension in the solvent in a
      predetermined solid/solvent ratio under controlled conditions. At the end of the
      solvent treatment period, MD powder was separated, dried and screened. Changes in
      the solid-state properties of surface-treated MD were monitored using flowability
      measurements, scanning electron microscopy, thermal analysis and dissolution
      rate. Further, photostability testing, according to the ICH guidelines, was
      conducted using compressed disks of MD treated with solvents in the absence and
      presence of antioxidants, namely ascorbic acid, butylated hydroxytoluene (BHT)
      and cysteine HCl. The color change (DeltaE) was determined according to the
      CIELAB system. Surface treatment of MD drug substance with ethanol, methanol and
      isopropanol resulted in a marked improvement in flowability which was associated
      with morphological crystalline changes. Treatment of MD with methanol provided
      free flowing spherical agglomerates. Disks of solvent-treated MD showed improved
      photostability which was further potentiated by the inclusion of antioxidants,
      although only traces of the antioxidant were retained in the treated powder.
      Tablets containing MD surface treated with methanol containing a mixture of 2%
      ascorbic acid and 0.2% BHT were prepared by direct compression using a simple
      formula. The tablets conformed to official requirements.

PMID- 16289574
TI  - Effects of absorption promoters on insulin absorption through colon-targeted
      delivery.
AB  - The aim of this study were to investigate the effect of sodium glycocholate (GC
      Na) as an absorption promoter and the effects of the co-administration of GC-Na
      and various absorption promoters on orally administered insulin absorption
      utilizing a colon-targeted delivery system. The system containing insulin and GC
      Na (CDS) was administered to dogs, and plasma glucose and insulin levels were
      then measured at 24h after administration. For CDS, the C(max) in plasma glucose
      level was significantly higher than a reference formulation without GC-Na. The
      pharmacological availability for CDS was not significantly higher than the
      reference formulation. In contrast, CDS with poly(ethylene oxide) as a gelling
      agent (CDSP) showed prolonged hypoglycemia effects. The pharmacological
      availability was 5.5% and significantly different from the reference formulation.
      The absolute bioavailability for CDS was 0.25%, and for CDSP it was 0.42%.
      Consequently, the results of this study demonstrated that colon-specific delivery
      of insulin with GC-Na was more effective in increasing hypoglycemic effects after
      oral administration, and the combination of GC-Na and poly(ethylene oxide) tended
      to prolong the colonic absorption of insulin and might be more effective for
      improvement of orally administered insulin absorption utilizing the colon
      targeted delivery system.

PMID- 16289575
TI  - Solution structure of isoform 1 of Roadblock/LC7, a light chain in the dynein
      complex.
AB  - Roadblock/LC7 is a member of a class of dynein light chains involved in
      regulating the function of the dynein complex. We have determined the three
      dimensional structure of isoform 1 of the mouse Roadblock/LC7 cytoplasmic dynein
      light chain (robl1_mouse) by NMR spectroscopy. In contrast to a previously
      reported NMR structure of the human homolog with 96% sequence identity (PDB
      1TGQ), which showed the protein as a monomer, our results indicate clearly that
      robl1 exists as a symmetric homodimer. The two beta3-strands pair with each other
      and form a continuous ten-stranded beta-sheet. The 25-residue alpha2-helix from
      one subunit packs antiparallel to that of the other subunit on the face of the
      beta-sheet. Zipper-like hydrophobic contacts between the two helices serve to
      stabilize the dimer. Through an NMR titration experiment, we localized the site
      on robl1_mouse that interacts with the 40 residue peptide spanning residues 243
      through 282 of IC74-1_rat. These results provide physical evidence for a
      symmetrical interaction between dimeric robl1 and the two molecules of IC74-1 in
      the dynein complex.

PMID- 16289577
TI  - Radical prostatectomy for early prostate cancer improves long term survival.

PMID- 16289576
TI  - Assembly of TbetaRI:TbetaRII:TGFbeta ternary complex in vitro with receptor
      extracellular domains is cooperative and isoform-dependent.
AB  - Transforming growth factor-beta (TGFbeta) isoforms initiate signaling by
      assembling a heterotetrameric complex of paired type I (TbetaRI) and type II
      (TbetaRII) receptors on the cell surface. Because two of the ligand isoforms
      (TGFbetas 1, 3) must first bind TbetaRII to recruit TbetaRI into the complex, and
      a third (TGFbeta2) requires a co-receptor, assembly is known to be sequential,
      cooperative and isoform-dependent. However the source of the cooperativity
      leading to recruitment of TbetaRI and the universality of the assembly mechanism
      with respect to isoforms remain unclear. Here, we show that the extracellular
      domain of TbetaRI (TbetaRI-ED) binds in vitro with high affinity to complexes of
      the extracellular domain of TbetaRII (TbetaRII-ED) and TGFbetas 1 or 3, but not
      to either ligand or receptor alone. Thus, recruitment of TbetaRI requires
      combined interactions with TbetaRII-ED and ligand, but not membrane attachment of
      the receptors. Cell-based assays show that TbetaRI-ED, like TbetaRII-ED, acts as
      an antagonist of TGFbeta signaling, indicating that receptor-receptor interaction
      is sufficient to compete against endogenous, membrane-localized receptors. On the
      other hand, neither TbetaRII-ED, nor TbetaRII-ED and TbetaRI-ED combined, form a
      complex with TGFbeta2, showing that receptor-receptor interaction is insufficient
      to compensate for weak ligand-receptor interaction. However, TbetaRII-ED does
      bind with high affinity to TGFbeta2-TM, a TGFbeta2 variant substituted at three
      positions to mimic TGFbetas 1 and 3 at the TbetaRII binding interface. This
      proves both necessary and sufficient for recruitment of TbetaRI-ED, suggesting
      that the three different TGFbeta isoforms induce assembly of the heterotetrameric
      receptor complex in the same general manner.

PMID- 16289578
TI  - Characterization of commercial laminin preparations from human placenta in
      comparison to recombinant laminins 2 (alpha2beta1gamma1), 8 (alpha4beta1gamma1),
      10 (alpha5beta1gamma1).
AB  - Laminins, a family of large heterotrimeric (alphabetagamma) proteins, are major
      components of basement membranes implicated in a variety of cellular functions.
      Different commercial laminin preparations isolated from human placenta have been
      widely used in functional studies but their molecular properties are poorly
      known. In the present study, we characterized several of these preparations by
      ELISA, silver staining and Western blotting, in comparison to mouse laminin 1
      (alpha1beta1gamma1), and recombinant human laminins 2 (alpha2beta1gamma1), 8
      (alpha4beta1gamma1) and 10 (alpha5beta1gamma1). The cell migration-promoting
      activity of different batches was also tested. The placenta laminin preparations
      differed from one another and consisted of highly fragmented proteins, a mixture
      of laminin isoforms, and/or contaminating fibronectin. Major functional
      differences between batches were also observed, reflecting molecular
      heterogeneity. Previous data obtained in functional studies using these
      preparations need to be interpreted with caution and may require revision, and
      future functional studies demand prior molecular characterization of the
      laminins, particularly their alpha-chain.

PMID- 16289579
TI  - Masking release for consonant features in temporally fluctuating background
      noise.
AB  - Consonant identification was measured for normal-hearing listeners using Vowel
      Consonant-Vowel stimuli that were either unprocessed or spectrally degraded to
      force listeners to use temporal-envelope cues. Stimuli were embedded in a steady
      state or fluctuating noise masker and presented at a fixed signal-to-noise ratio.
      Fluctuations in the maskers were obtained by applying sinusoidal modulation to:
      (i) the amplitude of the noise (1st-order SAM masker) or (ii) the modulation
      depth of a 1st-order SAM noise (2nd-order SAM masker). The frequencies of the
      amplitude variation fm and the depth variation f'm were systematically varied.
      Consistent with previous studies, identification scores obtained with unprocessed
      speech were highest in an 8-Hz, 1st-order SAM masker. Reception of voicing and
      manner also peaked around fm=8 Hz, while the reception of place of articulation
      was maximal at a higher frequency (fm=32 Hz). When 2nd-order SAM maskers were
      used, identification scores and received information for each consonant feature
      were found to be independent of f'm. They decreased progressively with increasing
      carrier modulation frequency fm, and ranged between those obtained with the
      steady state and the 1st-order SAM maskers. Finally, the results obtained with
      spectrally degraded speech were similar across all types of maskers, although an
      8% improvement in the reception of voicing was observed for modulated maskers
      with fm < 64 Hz compared to the steady-state masker. These data provide
      additional evidence that listeners take advantage of temporal minima in
      fluctuating background noises, and suggest that: (i) minima of different
      durations are required for an optimal reception of the three consonant features
      and (ii) complex (i.e., 2nd-order) envelope fluctuations in background noise do
      not degrade speech identification by interfering with speech-envelope processing.

PMID- 16289580
TI  - Optimal harvesting and optimal vaccination.
AB  - Two optimization problems are considered: Harvesting from a structured population
      with maximal gain subject to the condition of non-extinction, and vaccinating a
      population with prescribed reduction of the reproduction number of the disease at
      minimal costs. It is shown that these problems have a similar structure and can
      be treated by the same mathematical approach. The optimal solutions have a 'two
      window' structure: Optimal harvesting and vaccination strategies or policies are
      concentrated on one or two preferred age classes. The results are first shown for
      a linear age structure problem and for an epidemic situation at the uninfected
      state (minimize costs for a given reduction of the reproduction number) and then
      extended to populations structured by size, to harvesting at Gurtin-MacCamy
      equilibria and to vaccination at infected equilibria.

PMID- 16289581
TI  - Amygdaloid GABA, not glutamate neurotransmission or mRNA transcription controls
      footshock-associated fear arousal in the acoustic startle paradigm.
AB  - In Pavlovian conditioning the fear-evoking properties of the aversive
      unconditioned stimulus are represented by the conditioned stimulus. A major
      challenge for theories of classical fear conditioning has been to understand how
      associations are formed between a conditioned stimulus and unconditioned
      stimulus. Although the cellular mechanisms in the amygdala that underlie fear
      learning have received considerable attention relatively little is known about
      the neural substrates underlying unconditioned stimulus-associated fear. In the
      present study we examined the role of GABA(A), N-methyl-D-aspartic acid and non-N
      methyl-D-aspartic acid receptors, and protein synthesis inhibition on the
      immediate fear arousal produced by footshock as measured by the shock
      sensitization of acoustic startle. Laboratory rats showed shock-enhanced startle
      after infusion into the basolateral amygdala of the N-methyl-D-aspartic acid
      receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (5.0 microg), the non
      N-methyl-D-aspartic acid receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione
      disodium (5.0 microg) and the protein synthesis inhibitor anisomycin (80.0
      microg). We concluded that fear arousal provoked by footshock is not mediated by
      glutamate neurotransmission in the amygdala and does not involve de novo protein
      synthesis. Bilateral infusion into the basolateral amygdala of the GABA(A)
      receptor agonist muscimol in doses ranging from 0.001-0.5 microg reliably blocked
      the shock sensitization of acoustic startle responding. None of the muscimol
      doses altered shock reactivity amplitudes indicating the normal perception of
      footshock. The muscimol results were interpreted to suggest that decreased GABA
      neurotransmission in the amygdala may be essential for the neural causation of
      fear that is acquired and expressed by conditioned stimuli.

PMID- 16289582
TI  - Changes in response to spinal cord injury with development: vascularization,
      hemorrhage and apoptosis.
AB  - Chick embryos are capable of functional spinal cord regeneration following crush
      injury until embryonic day 13. Developmental changes occurring thereafter result
      in failure to regenerate. Secondary injury mechanisms can result in apoptotic
      cell death and make a major contribution to cell loss after trauma. We report
      here that around embryonic day 13 there is a dramatic increase in blood vessel
      numbers in the spinal cord, and that the extent of hemorrhage in response to
      injury increases with developmental age. This is paralleled by increased
      apoptosis and subsequent cavitation in spinal cords injured at embryonic day 15
      as compared with embryonic day 11. Following spinal cord injury at embryonic day
      15, apoptotic cell death is extensive and spreads to the same extent as the
      hemorrhage. When hemorrhage is reduced by treatment with the hemostatic drug
      desmopressin the extent of apoptosis and cavity formation in spinal cords injured
      at embryonic day 15 decreases. Furthermore, manipulations of embryonic day 11
      spinal cords that increase hemorrhage also increase apoptosis and result in
      cavitation in contrast to the effective repair typical of this stage. Altogether
      these results suggest that cavity formation occurring at developmental stages non
      permissive for regeneration is largely due to changes in the extent of apoptosis
      that are related to vascularization and hemorrhage.

PMID- 16289583
TI  - Insomnia following hypocretin2-saporin lesions of the substantia nigra.
AB  - The neuropeptide hypocretin, also known as orexin, has been implicated in waking
      since its deletion leads to the sleep disorder narcolepsy. Hypocretin neurons
      project to major arousal areas, and in an effort to determine which region is
      responsible for the changes in sleep-wake architecture we have developed the
      neurotoxin hypocretin2-saporin, which lesions hypocretin receptor bearing
      neurons. Here, in rats, we investigate the effects of hypocretin2-saporin lesions
      of the substantia nigra and ventral tegmental area in the regulation of sleep and
      wakefulness. Bilateral injection of hypocretin2-sap into both the ventral
      tegmental area and substantia nigra (92 and 184 ng/microl, 0.25 microl in the
      ventral tegmental area and 0.5 microl in the substantia nigra) or into the
      substantia nigra alone (184 ng/microl, 0.5 microl) produced insomnia. The
      insomnia seemed to be associated with a large increase in locomotion on days 4
      and 6 postinjection, as hyperactivity and stereotypic movements were consistently
      observed on the video recordings in all lesioned rats. In these rats, a nearly
      complete loss of both tyrosine hydroxylase and neuron-specific nuclear protein
      (neuronal nuclei) immunoreactive cells in the substantia nigra as well as
      diminution of tyrosine hydroxylase-immunoreactive fibers in the caudate putamen
      was found. Following bilateral injection of hypocretin2-sap at a lower
      concentration (46 ng/microl, 0.25 microl in the ventral tegmental area and 0.5
      microl in the substantia nigra), very little reduction in the number of tyrosine
      hydroxylase- and neuronal nuclei-immunoreactive neurons and only a temporary
      increase in wakefulness (17.4% increase during light-off period on day 6
      postinjection) were observed. Ventral tegmental area lesions (184 ng/mul of
      hypocretin2-sap, 0.25 microl, bilateral injections) did not produce significant
      changes in sleep, although most of the tyrosine hydroxylase- and neuronal nuclei
      immunoreactive neurons in the ventral tegmental area were destroyed. Insomnia
      following hypocretin2-sap lesions of the substantia nigra could be secondary to
      increased motor activity resulting from reduction of tonic inhibitory control by
      the substantia nigra.

PMID- 16289584
TI  - Neurofilament high molecular weight-green fluorescent protein fusion is normally
      expressed in neurons and transported in axons: a neuronal marker to investigate
      the biology of neurofilaments.
AB  - The carboxy-terminal side arm of the neurofilament high subunit consists of a
      highly phosphorylated domain and a negatively charged region. Multiple evidences
      suggested that these domains are essential for the axonal phosphorylation and
      transport of neurofilaments and play a role in their abnormal accumulation
      following chemical intoxication or during neurodegenerative disorders such as
      amyotrophic lateral sclerosis. In order to investigate the consequences of
      altering this side arm of neurofilament high subunit we used a fusion protein
      (neurofilament high subunit-green fluorescent protein) between the mouse
      neurofilament high subunit missing a major part of the C-terminal domain and the
      reporter green fluorescent protein. In cell culture and in transgenic mice this
      fusion protein co-assembles and co-distributes with the endogenous intermediate
      filament network. Conditions known to disturb the cytoskeleton were also found to
      alter the distribution of the fusion protein in cell cultures. In transgenic mice
      the expression of the transgene evaluated by its fluorescent properties was found
      to be restricted to neurons, where the neurofilament high subunit-green
      fluorescent protein fusion protein is axonally transported. Biochemical
      approaches showed that the fusion protein is phosphorylated and co-purified with
      neurofilaments. Despite the presence of such an neurofilament high subunit-green
      fluorescent protein fusion protein, the axonal cytoskeletal density and the
      axonal caliber were not altered. Together these data show that removal of this
      portion of neurofilament high subunit does not affect the capacity of
      neurofilament high subunit to assemble and to be transported into axons,
      suggesting that this sequence is involved in another function. Moreover, the
      fluorescent properties of this fusion protein represent a useful marker.

PMID- 16289585
TI  - Estrogen prevents glutamate-induced apoptosis in C6 glioma cells by a receptor
      mediated mechanism.
AB  - Estrogen-mediated neuroprotection is well established; however, no single
      mechanism of action for this effect has yet been established. As glial cells are
      integral for both the intact and injured nervous system, we hypothesized that
      estrogen-mediated neuroprotection may partly be attributed to attenuation of
      glial cell apoptosis, allowing them to protect neurons following injury. To
      assess the protective effects of estrogen on glia, C6 rat glioma cells were
      treated for 24 h with 500 microM glutamate. Cell viability was determined by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and apoptosis
      was confirmed by cell morphology and DNA fragmentation. Pretreatment with 10 nM
      17beta-estradiol (estrogen) increased cell viability and attenuated apoptosis.
      Treatment with the stereoisomer 17alpha-estradiol, or estrogen plus estrogen
      receptor antagonist ICI 182,780, was significantly less effective, indicating
      that cytoprotection was receptor-mediated. Estrogen treatment upregulated
      expression of estrogen receptor alpha. Cell impermeable bovine serum albumin
      conjugated estrogen was also protective, indicating activation of estrogen
      receptors on the cell membrane. Intracellular free [Ca2+] was increased after
      glutamate treatment. This increase was attenuated in cells pretreated with
      estrogen. Glutamate increased the activity of pro-apoptotic proteases, such as
      calpain and caspase-3, and these protease activities were significantly
      attenuated by estrogen. The mechanism by which estrogen decreased intracellular
      Ca2+ was examined by assaying cell viability after using inhibitors that either
      blocked extracellular Ca2+ influx or prevented the release of intracellular Ca2+
      stores. While several inhibitors increased cell viability in glutamate-treated
      cells, none were as protective as estrogen, and estrogen co-treatment
      significantly increased cell viability. These findings indicate that estrogen
      mediated cytoprotection may be related to effects on Ca2+ entry but that these
      effects are not limited to any one of these Ca2+ entry points alone.

PMID- 16289587
TI  - Status epilepticus induces time-dependent neuronal and astrocytic expression of
      interleukin-1 receptor type I in the rat limbic system.
AB  - Interleukin-1beta is rapidly synthesized by glia after the induction of seizures.
      Recent evidence shows that endogenous IL-1beta has proconvulsant actions mediated
      by interleukin-1 receptor type I. This receptor also mediates interleukin-1beta
      effects on neuronal susceptibility to neurotoxic insults. In this study, we
      investigated the basal and seizure-induced expression of interleukin-1 receptor
      type I in rat forebrain to identify the cells targeted by interleukin-1beta
      during epileptic activity. Self-sustained limbic status epilepticus was induced
      in rats by electrical stimulation of the ventral hippocampus. Interleukin-1
      receptor type I immunoreactivity was barely detectable in neurons in control
      brain tissue. During status epilepticus, interleukin-1 receptor type I was
      induced in the hippocampal neurons firstly, and several hours later in astrocytes
      localized in limbic and extralimbic areas. Neuronal interleukin-1 receptor type I
      expression in the hippocampus outlasted the duration of spontaneous
      electroencephalographic seizure and was not observed in degenerating neurons.
      Astrocytic expression occurred transiently, between six and 18 h after the
      induction of status epilepticus and was invariably found in regions of neuronal
      damage. These time-dependent, cell- and region-specific changes in interleukin-1
      receptor type I expression during status epilepticus suggest that interleukin-1
      receptor type I in neurons mediates interleukin-1beta-induced fast changes in
      hippocampal excitability while interleukin-1 receptor type I receptors in
      astrocytes may mediate interleukin-1beta effects on neuronal survival in hostile
      conditions.

PMID- 16289586
TI  - Modeling depression: social dominance-submission gene expression patterns in rat
      neocortex.
AB  - Gene expression profiles in the cortex of adult Long-Evans rats as a function of
      a stressful social loss and victory in inter-male fighting encounters were
      examined. This social dominance and subordination model has been postulated to
      simulate early changes in the onset of depression in the losers. Microarrays were
      fabricated containing 45mer oligonucleotides spotted in quadruplicate and
      representing 1178 brain-associated genes. Dynamic range, discrimination power,
      accuracy and reproducibility were determined with standard mRNA "spiking"
      studies. Gene expression profiles in dominant and subordinate animals were
      compared using a "universal" reference design [Churchill GA (2002) Fundamentals
      of experimental design for cDNA microarrays. Nat Genet 32 (Suppl):490-495]. Data
      were analyzed by significance analysis of microarrays using rank scores [Tusher
      VG, Tibshirani R, Chu G (2001) Significance analysis of microarrays applied to
      the ionizing radiation response. Proc Natl Acad Sci USA 98:5116-5121; van de Wiel
      MA (2004) Significance analysis of microarrays using rank scores. Kwantitatieve
      Methoden 71:25-37]. Ontological analyses were then performed using the GOMiner
      algorithm [Zeeberg BR, Feng W, Wang G, Wang MD, Fojo AT, Sunshine M, Narasimhan
      S, Kane DW, Reinhold WC, Lababidi S, Bussey KJ, Riss J, Barrett JC, Weinstein JN
      (2003) GoMiner: a resource for biological interpretation of genomic and proteomic
      data. Genome Biol 4(4):R28]. And finally, genes of special interest were further
      studied using quantitative reverse transcriptase polymerase chain reaction.
      Twenty-two transcripts were statistically significantly differentially expressed
      in the neocortex between dominant and subordinate animals. Ontological analyses
      revealed that significant gene changes were clustered primarily into functional
      neurochemical pathways associated with protein biosynthesis and cytoskeletal
      dynamics. The most robust of these were the increased expression of interleukin
      18, heat shock protein 27, beta3-tubulin, ribosome-associated membrane protein 4
      in subordinate animals. Interleukin-18 has been found to be over-expressed in
      human depression and panic disorder as well as other physiological stress
      paradigms [Takeuchi M, Okura T, Mori T, Akita K, Ohta T, Ikeda M, Ikegami H,
      Kurimoto M (1999) Intracellular production of interleukin-18 in human epithelial
      like cell lines is enhanced by hyperosmotic stress in vitro. Cell Tissue Res
      297(3):467-473] and heat shock proteins have been shown to be involved in the
      pathogenesis of many neurodegenerative and psychiatric disorders [Iwamoto K,
      Kakiuchi C, Bundo M, Ikeda K, Kato T (2004) Molecular characterization of bipolar
      disorder by comparing gene expression profiles of postmortem brains of major
      mental disorders. Mol Psychiatry 9(4):406-416; Pongrac JL, Middleton FA, Peng L,
      Lewis DA, Levitt P, Mirnics K (2004) Heat shock protein 12A shows reduced
      expression in the prefrontal cortex of subjects with schizophrenia. Biol
      Psychiatry 56(12):943-950]. Thus, the gene expression changes that we have
      observed here are consistent with and extend the observations found in the
      clinical literature and link them to the animal model used here thereby
      reinforcing its use to better understand the genesis of depression and identify
      novel therapeutic targets for its treatment.

PMID- 16289588
TI  - Effects of intrathecal and i.c.v. administration of neuropeptide W-23 and
      neuropeptide B on the mechanical allodynia induced by partial sciatic nerve
      ligation in rats.
AB  - Neuropeptide W-23 and neuropeptide B are each an endogenous ligand of GPR7. GPR7
      mRNA has been detected in regions of the cortex, the hippocampus, the
      hypothalamus and the spinal cord in the rat. GPR7 receptor has structural
      features in common with both opioid and somatostatin receptors. In the present
      study, the effects of intrathecal and i.c.v. application of neuropeptide W-23 and
      neuropeptide B on the level of mechanical allodynia induced by partial sciatic
      nerve ligation were tested in rats. The level of mechanical allodynia was
      measured using von Frey filaments. Intrathecal injection of either neuropeptide W
      23 or neuropeptide B attenuated the level of mechanical allodynia in a dose
      dependent manner at a dose between 0.1 and 10 microg, but i.c.v. injection of
      either neuropeptide W-23 or neuropeptide B had no effect on the level of
      mechanical allodynia at a dose between 3 and 30 microg. The effect of intrathecal
      administration of either 10 microg of neuropeptide W-23 or 10 microg of
      neuropeptide B was not antagonized by i.p. injection of 1 mg/kg of naloxone.
      Immunohistochemical examination revealed that neuropeptide W-23 was expressed
      mainly in the small- to medium-sized neuronal profiles in the dorsal root
      ganglion and that partial sciatic nerve injury decreased the percentage of
      neuropeptide W-23-like immunoreactivity positive neuronal profiles that were
      labeled by IB4. These data suggest that neuropeptide W-23 is involved in the
      nociceptive transmission in spinal cord and that both spinally-applied
      neuropeptide W-23 and spinally-applied neuropeptide B produce anti-allodynic
      effects in the partial sciatic nerve ligation model in rat.

PMID- 16289589
TI  - Sustained attention measurements in obstructive sleep apnea and risk of traffic
      accidents.
AB  - The aim of this study was to identify associations between performance on driving
      simulators, subject sleep complaints, and risk of traffic accidents in a
      population undergoing OSAS investigation. PATIENTS AND METHODS: One hundred and
      twenty-nine consecutive adult patients with a driver's licence and clinical
      symptoms of OSA were initially recruited from the hospital waiting list. Each
      patient was applied a polysomnography and two driving tests. Patients also
      completed a Basic Nordic Sleep Questionnaire, Epworth Sleepiness Scale and SF-36
      quality of life questionnaire. RESULTS: Poor performance in vigilance was
      associated with alcohol intake (OR 4.41, 95% CI 1.13-17.20, P<0.05), and SF-36
      vitality dimension (OR 0.97, 95% CI 0.94-0.99, P<0.05). Poor tracking error was
      associated with female gender (OR 6.79, 95% CI 1.37-33.65, P<0.05), alcohol
      intake (OR 3.32, 95% CI 1.03-10.63, P<0.05), and a history of accidents in the
      previous year (OR 5.84, 95% CI 1.33-25.68, P<0.05). Poor reaction time was only
      associated with age (OR 1.12, 95% CI 1.03-1.21, P<0.01). When all three
      performance measures were studied jointly, only reaction time was associated with
      self-reported dozing while driving (OR 5.39, 95% CI 1.10-26.32, P<0.05), and
      irresistible tendency to fall asleep was associated with poor tracking error
      (P<0.05). CONCLUSIONS: Performance on driving simulators is associated with some
      sleep complaints in OSA patients. Although these measures are not directly
      associated to traffic accidents, they are, in fact, associated to related
      circumstances such as dozing while driving and falling asleep while driving.

PMID- 16289591
TI  - Are surgical residents prepared for mass casualty incidents?
AB  - OBJECTIVE: We hypothesized that resident education is inadequate with respect to
      management of mass casualty incidents that may involve chemical, biological, and
      nuclear exposures. METHODS: Chief level residents in surgery (n = 10), emergency
      medicine (n = 10), and anesthesia (n = 8) were asked to complete a survey
      questionnaire. Responses were tabulated and statistically analyzed with Mann
      Whitney Rank Sum, Student's t test, and Kruskal-Wallis one-way analysis of
      variance. RESULTS: All of the residents were similar with respect to age, sex,
      and intended setting of clinical practice. Only a single resident reported
      military experience. Two residents (7.1%) had administered medical care while
      wearing a protective suit. Compared with emergency medicine residents, surgical
      residents reported significantly less formal teaching in mass casual incidents (P
      = 0.02), trauma triage (P = 0.01), and nuclear, biological, chemical agents (P =
      0.002). When surgical residents were compared with anesthesia residents, there
      was significantly less training for surgical residents in nuclear, chemical, and
      biological agents (P = 0.02). Multiple/mass casualty incident experience did not
      differ between residents. However, the most common incident involved only three
      to five patients with blunt trauma. Emergency medicine residents were
      significantly more comfortable in treating patients with exposure to anthrax (P =
      0.01), sarin (P = 0.04), and nuclear exposure (P = 0.01). CONCLUSIONS: Surgical
      residents have significantly less formal training in mass casualties, triage, and
      chemical, biological, and nuclear exposures than residents in other specialties.
      Therefore, surgical residents are less comfortable treating these types of
      patients. Because surgeons often are expected to take leadership roles in mass
      casualty incidents, surgical education should be modified to match or exceed that
      of other specialties.

PMID- 16289590
TI  - Single breath N2-test and exhaled nitric oxide in men.
AB  - The N(2) slope is an index of inhomogeneous distribution of ventilation and has
      been suggested to be suited for early testing of chronic obstructive pulmonary
      disease (COPD) in smokers. The aim of the present study was to examine the
      association between the fraction of exhaled nitric oxide (FENO) and the N(2)
      slope in a random population of smoking and non-smoking men. Altogether 57
      subjects were included in the study, 24 never-smokers, seven ex-smokers and 26
      current smokers. Subjects were examined twice, in 1995 when they regarded
      themselves as healthy, and in a follow-up in 2001. Spirometry, N(2) slope and
      high-resolution computed tomography (HRCT) were performed in 1995 while the
      follow-up examination included also measurement of FENO. The FENO value was
      significantly lower and the N(2) slope higher in current smokers. In smokers but
      not in never- or ex-smokers FENO was correlated to the difference in N(2) slope
      between 1995 and 2001 (r(s)=0.49, P=0.01). We analysed the data by multiple
      linear regression adjusted for smoking, mild respiratory symptoms and inhaled
      steroids. There were significant associations between FENO and the N(2) slope
      both in 1995 and in 2001. The strongest association was found to exist with the
      change in N(2) slope during these years. Sixteen of the subjects could be
      classified as having COPD, six with mild and ten with moderate COPD. There was a
      trend for an increase in N(2) slope with increased severity of COPD; among
      subjects with no COPD the N(2) slope in 2001 was 2.3% N(2)/L, and those with mild
      and moderate COPD had 2.5% N(2)/L and 3.9% N(2)/L, respectively (P=0.0004). No
      such trend was seen for FENO (17.8, 15.5 and 20.3 parts per billion (ppb),
      respectively, P=0.8). The results show that FENO is associated with the N(2)
      slope, indicating that FENO reflects inflammatory changes in the peripheral
      airways of both non-smoking and smoking subjects.

PMID- 16289592
TI  - Modulation of macrophage nitric oxide production by prostaglandin D2.
AB  - BACKGROUND: Nitric oxide and prostaglandins readily become activated in response
      to inflammatory events. The overproduction of nitric oxide is detrimental to the
      host. The present study was conducted to examine whether prostaglandin D(2)
      (PGD(2)) modulates nitric oxide production in macrophages in response to an
      inflammatory stimulus. METHODS: Cultures of RAW 264.7 murine macrophages were
      exposed to Escherichia coli lipopolysaccharide (LPS, 0.01 and 1.0 microg/ml)
      before and after exposure to PGD(2) (0.01 to 10 nmol). After 24-h incubation,
      supernatants were collected and nitrite was quantitated by Greiss reaction as a
      measure of nitric oxide synthesis. Inducible nitric oxide synthase (iNOS) protein
      was measured by Western blot analysis. RESULTS: Macrophages exposed to 0.01 and
      1.0 microg/ml LPS produced 8.3 +/- 0.2 and 15.0 +/- 1.4 nmol/1.1 x 10(6) cells/24
      h of nitrite, respectively. The simultaneous addition of PGD(2) with LPS
      inhibited nitrite production in a dose-dependent fashion and suppressed iNOS
      protein expression. A strong time effect was also exhibited when macrophages were
      incubated with PGD(2) 1 hour before as compared to 7 hours after the addition of
      LPS (0.01 or 1.0 microg/ml), indicating that the earlier the time PGD(2) was
      added to the culture media, the greater the inhibition. Prostaglandin D(2) had
      the capacity to block nitrite synthesis even when added as much as 7 hours after
      an LPS challenge. Blocking endogenous prostaglandins, using indomethacin (10
      microM), suppressed nitrite production. CONCLUSION: Exogenous PGD(2) caused dose-
      and time-dependent decreases in LPS-stimulated nitrite production by RAW 264.7
      macrophages by hindering iNOS protein expression. Conversely, the endogenous
      prostaglandins released by these same cells in response to an LPS challenge
      stimulated nitrite production, which may consequently dampen the inhibitory
      actions of exogenous PGD(2).

PMID- 16289594
TI  - General handling and anesthesia for experimental surgery in pigs.
AB  - The pig is a common large animal for experimental settings in many fields of
      surgery. In experimental surgery, there is a need for different narcotic
      procedures depending on the complexity of the surgical investigation. Narcotic
      procedures have to be safe, easy to handle, and should not influence the
      experimental results. We hereby present important aspects of handling and
      narcotic procedures for pigs. The aim of this publication is to supply an
      introduction for young surgical investigators who are planning or already have
      started investigations using pigs as an experimental animal. This publication is
      based on our institutional experience of narcotic and surgical procedures in more
      than 400 cases.

PMID- 16289593
TI  - Development of peritoneal adhesions in macrophage depleted mice.
AB  - BACKGROUND: We present a new mouse model for the study of peritoneal adhesions
      using macrophage Fas-induced apoptosis (Mafia) transgenic mice expressing a Fas
      FKBP construct under control of the murine c-fms promoter. Mafia mice allow
      systemic macrophage depletion by dimerization of Fas with a synthetic dimerizer,
      AP20187. Results demonstrate that macrophage depletion in Mafia mice induces
      peritoneal adhesion formation when the peritoneal cavity is also exposed to an
      irritant. The Mafia mouse model presents a reproducible, non-surgical approach
      for research in adhesion formation and prevention. MATERIALS AND METHODS: Mafia
      mice were treated with AP20187 using an intravenous (i.v.) or intraperitoneal
      (i.p.) injection. Control groups included mock-treated Mafia mice and both
      AP20187 and mock-treated wild type mice. Seven days after treatment, mice were
      observed for the presence of adhesions. RESULTS: After i.p. injection with
      AP20187, 76% of Mafia mice developed adhesions whereas none of the mock-treated
      Mafia or wild-type mice developed adhesions, and only one AP20187-treated wild
      type mouse (5.8%) developed a mild adhesion. Mafia mice treated with AP20187 i.v.
      exhibited macrophage depletion not significantly different than i.p. treated
      mice, but did not develop adhesions. In contrast, Mafia mice treated with AP20187
      i.v. developed adhesions when diluent was also injected into the peritoneal
      cavity, whereas i.p diluent alone had no effect. CONCLUSION: Macrophage
      depletion, combined with a peritoneal irritant, results in peritoneal adhesion
      formation in transgenic Mafia mice. Macrophages appear to play a protective role
      in the development and/or repair of peritoneal adhesions.

PMID- 16289595
TI  - In vivo complete neural isolation of the rat jejunoileum: a simple model to study
      denervation sequelae of intestinal transplantation.
AB  - BACKGROUND: Our aim was to develop and validate a technically easy, reliable, and
      reproducible method of complete jejunoileal denervation in the rat to allow study
      of the physiologic effects of intestinal transplantation devoid of immunologic
      phenomena and ischemia/reperfusion injury. MATERIALS AND METHODS: Six adult
      Sprague-Dawley rats underwent transection and reanastomosis of the proximal
      jejunum and proximal colon, transection of all neurolymphatic tissues at the base
      of the mesentery, stripping adventitia off the superior mesenteric artery and
      vein, and radial transection of the intervening mesenteries, thereby denervating
      the jejunoileum in situ without disrupting blood flow. Three rats each were
      sacrificed 1 and 6 months later. Intestinal smooth muscle from the still
      innervated duodenum and the denervated jejunum, mid-small bowel, and ileum was
      compared to corresponding tissues from a normal rat for tyrosine hydroxylase
      immunohistochemistry, a marker of extrinsic innervation. RESULTS: One and six
      months after denervation, all duodenal samples demonstrated normal tyrosine
      hydroxylase immunostaining. In contrast, tyrosine hydroxylase immunoreactivity
      was undetectable in jejunum, mid-small bowel, or ileum of rats at 1 month and 2
      of the 3 rats at 6 months; 1 rat at 6 months had low levels of tyrosine
      hydroxylase immunoreactivity at the mesenteric border of jejunum and mid small
      bowel. CONCLUSION: This simple technique of in situ neural isolation effectively
      and reproducibly achieves complete extrinsic denervation of the entire rat
      jejunoileum. Low levels of neural regeneration may be present 6 months after
      denervation.

PMID- 16289596
TI  - Lysophosphatidic acid-induced effects in human colon carcinoma DLD1 cells are
      partially dependent on transactivation of epidermal growth factor receptor.
AB  - BACKGROUND: Lysophosphatidic acid (LPA) is a lipid mediator of diverse effects on
      various cells. LPA is well known to induce phosphorylation of the epidermal
      growth factor receptor (EGFR), which is termed transactivation, in some cell
      types. In this study, we investigated the contribution of EGFR transactivation in
      LPA-induced responses in colon cancer DLD1 cells. MATERIALS AND METHODS:
      Immunoprecipitation was performed to investigate whether LPA induced EGFR
      phosphorylation. Then, we investigated LPA-induced migration and IL-8 secretion
      in DLD1 cells. Migration was measured in a modified Boyden chamber and IL-8
      secretion was measured by ELISA. In these experiments we used an EGFR inhibitor,
      AG1478 or matrix metalloproteinase (MMP) inhibitor, GM6001. RESULTS:
      Immunoprecipitation analysis revealed that LPA induced a significant level of
      tyrosine phosphorylation of EGFR in DLD1 cells. The LPA-induced phosphorylation
      of EGFR was almost completely abrogated by either AG1478 or GM6001. LPA induced
      significant migration and IL-8 secretion in DLD1, both of which were
      significantly inhibited by AG1478 or GM6001. However, the inhibitory effects were
      only partial (migration; 29% +/- 2%, 32 +/- 13% inhibition, IL-8 secretion; 33%
      +/- 1%, 26% +/- 5% inhibition, respectively). CONCLUSION: These results clearly
      indicate that LPA acts upstream of EGFR and compensates the EGF signal and
      antagonism of the EGF signal cannot completely block tumor progression in colon
      cancer cells. Blockade of the LPA signal may have clinical significance in the
      treatment of colon cancer.

PMID- 16289597
TI  - Modulation of neutrophil apoptosis in plasma of patients after orthognathic
      surgery.
AB  - BACKGROUND: Human neutrophils undergo rapid apoptosis during in vitro culture.
      The aim of this study was to investigate the role of interleukin-8 (IL-8) on
      neutrophil apoptosis in surgery-induced inflammation. MATERIALS AND METHODS:
      Blood samples were drawn from 21 patients with mandibular prognathism 2 days
      before, and 1 and 5 days after orthognathic surgery. The IL-8 levels in the
      separated plasma were measured using an ELISA kit. The expression of two
      receptors for IL-8, CXCR1, and CXCR2, and their role in neutrophil apoptosis was
      evaluated using a flow cytometer. RESULTS: The IL-8 levels in the plasma were
      correlated with acute inflammatory markers, such as peripheral blood neutrophil
      counts and C-reactive protein levels. Both IL-8 receptors were markedly raised in
      patient-derived neutrophils 1 day post-operatively. Recombinant IL-8 (0-100
      ng/ml) suppressed apoptosis in fresh-isolated neutrophils from healthy donors
      dose-dependently. Neutrophil apoptosis 1 day post-operatively was slightly
      accelerated in the presence of fetal bovine serum compared to the value 2 days
      pre-operatively and 5 days post-operatively. In contrast, in the presence of
      autogenous plasma, neutrophil apoptosis was significantly suppressed 1 day post
      operatively compared to the value 2 days pre-operatively and 5 days post
      operatively. Moreover, the anti-apoptotic effect of plasma on neutrophil
      apoptosis was partially decreased by the addition of anti-IL-8 neutralizing
      antibody. CONCLUSIONS: These results suggest that circulating neutrophils are
      susceptible to augmentation by IL-8 through the reinforcement of IL-8 receptors
      in acute inflammatory conditions. Furthermore, IL-8 may, in part, contribute to
      the regulation of neutrophil survival during the inflammatory response.

PMID- 16289598
TI  - Laparoscopic azygoportal disconnection procedure with a bipolar feedback
      controlled sealing system in a porcine model.
AB  - BACKGROUND: To examine the feasibility of a new, minimally invasive procedure for
      the devascularization of the proximal stomach and distal esophagus to prevent
      recurrent variceal bleeding in portal hypertension in a new animal model.
      MATERIAL AND METHODS: Portal hypertension was created by laparoscopic clip
      ligation of the portal vein on 20 pigs. After 2 weeks the azygoportal
      disconnection procedure was performed with the LigaSure-ATLAS instrument.
      RESULTS: There were 16 pigs out of 20 that survived both operations. Two died
      during introduction of anesthesia, one because of a cardiac arrest (second
      operation). One pig died resulting from necrosis of the gastric and esophageal
      wall. Autopsy (2 weeks later) showed that there was a complete arterial
      devascularization. At autopsy, none of the remaining 16 pigs had esophageal
      varices or necrosis of the stomach or esophagus. CONCLUSION: Laparoscopic
      azygoportal disconnection is a less invasive method for the prevention of
      rebleeding and seems to be safely performed with the LigaSure-ATLAS instrument.

PMID- 16289600
TI  - Detection of deletions flanked by short direct repeats in mitochondrial DNA of
      aging Drosophila.
AB  - Cumulative damage due to reactive oxygen species (ROS) in mitochondria,
      especially in mitochondrial DNA (mtDNA), would result in a decrease in
      mitochondrial respiratory function and contributes to the age-related decline in
      the physiological functioning of organisms. Previously, we reported the tissue
      specific accumulation of deleted mtDNA with age in Drosophila melanogaster. In
      the present study, to understand the mechanism by which mtDNA deletion is
      generated with age, nucleotide sequences of deleted mtDNA were determined.
      Consequently, 33 different sequences each containing a deletion were obtained
      from flies that were more than 55-day-old. Most of the deletions were found to be
      flanked by short direct repeats. The present results, together with those from
      other animals, suggest that there is a common mechanism generating mtDNA
      deletions through direct repeats.

PMID- 16289599
TI  - Effect of tea catechins on mitochondrial DNA 4977-bp deletions in human
      leucocytes.
AB  - The catechins in green tea have antioxidative and antimutagenic effects. We
      examined the effect of green tea enriched with catechins on the presence of
      mitochondrial DNA (mtDNA) with a common 4977-bp deletion mutation (mtDNA4977) in
      human leucocytes. Ten healthy females [aged 20.80 +/- 1.03 years] drank 350 ml of
      catechin-rich tea daily after supper for 5 weeks. Blood samples were collected
      twice before, and twice after 5 weeks of consuming the tea. Deletions in mtDNA
      were analyzed using the nested polymerase chain reaction (PCR). We identified a
      common mtDNA4977 deletion in nine participants before drinking the tea. However,
      this mtDNA4977 deletion was not evident in leucocytes from most of the
      participants 5 weeks after drinking the tea. Catechins found in tea might
      contribute to the maintenance of health status by reducing damage to mtDNA and by
      maintaining the capacity of mtDNA for oxidative phosphorylation.

PMID- 16289601
TI  - Vasoactivity and antioxidant properties of Microdesmis keayana roots.
AB  - Endothelial isoform of nitric oxide synthase (eNOS) mRNA expression increases in
      the corpora cavernosum, penile arteries and arterioles during erection. But eNOS
      expression and nitric oxide (NO), the product of its catalytic action, are
      inactivated by reactive oxygen species (ROS), especially by superoxide anion. ROS
      are involved in the impairment of endothelium-dependent relaxation and are
      responsible for some of the pathologies linked to erectile dysfunction (i.e.
      hypertension, atherosclerosis, etc.). While investigating Microdesmis keayana J.
      Leonard (Pandaceae) (syn. Microdesmis puberula Hook.f. ex. Planch.), used in
      African traditional medicine for erectile dysfunction, the hypotensive and the
      vasorelaxing properties of the aqueous extract of Microdesmis keayana (AEMK)
      were, respectively, tested using normotensive rabbits and aorta strips of guinea
      pigs in an organ bath experience. Interaction of AEMK in endothelial production
      of eNOS was measured by the quantitative polymerase chain reaction (QPCR)
      analysis. The scavenging activities versus ROS, such as superoxide anion (O(2)(.
      )), hydrogen peroxide (H(2)O(2)), hypochlorous acid (HOCl) and hydroxyl radical
      (HO.) were evaluated. Action of AEMK on cellular generation of superoxide anion
      was also tested in a physiopathology model of oxidative burst using human
      polymorphonuclear neutrophils (PMNs) stimulated by phorbol myristate acetate. The
      results showed that Microdesmis keayana roots had significant hypotensive and
      vasorelaxing properties. These properties are due to both antioxidant activities
      and stimulation of eNOS mRNA expression. Therefore, AEMK stimulated indirectly NO
      production in the vascular bed.

PMID- 16289602
TI  - Plectranthus: a review of ethnobotanical uses.
AB  - Plectranthus is a large and widespread genus with a diversity of ethnobotanical
      uses. The genus is plagued with numerous nomenclatural disharmonies that make it
      difficult to collate accurate data on the uses. The aim of this review is to
      gather together all ethnobotanical information on Plectranthus and to map the
      data onto the most up-to-date phylogenetic classification in order to see if
      there are similar uses among related species and hence provide a framework for
      the prediction and exploration of new uses of species. The uses of 62 species of
      Plectranthus were mapped onto a current phylogeny based on DNA sequence data. The
      phylogeny reveals two major Clades, 1 and 2. The members of Clade 1
      (corresponding to the formally recognized genus Coleus) were richer in number and
      diversity of uses than members of Clade 2 (comprising the remaining species of
      Plectranthus). The high incidence of synonymy can lead to problems in uncovering
      a species' ethnobotanical profile. About 30% of all citations of Plectranthus use
      a synonym and most of the synonyms are attributed to 10 of the most used species,
      9 of which are in Clade 1. Members of the 'Coleus' Clade are the most studied
      group both taxonomically and economically. The higher incidence of study may be
      as a result of the higher diversity of uses and the fact that species in Clade 1,
      such as Plectranthus barbatus, Plectranthus amboinicus and Plectranthus mollis,
      are geographically more widespread than those in Clade 2. Plectranthus species in
      Clade 1 are frequently used as medicines and are used to treat a range of
      ailments, particularly digestive, skin, infective and respiratory problems.
      Plectranthus used as foods, flavours, fodder and materials are also mostly found
      in Clade 1. Monoterpenoids, sesquiterpenoids, diterpenoids and phenolics have
      been reported in species of Plectranthus. The abietane diterpenoids are the most
      diverse of the diterpenoids isolated from species of Plectranthus. The labdane
      diterpenoid, forskolin, occurs in Plectranthus barbatus and could explain some of
      the traditional uses of this species. This review highlights the fact that not
      enough is known about the chemistry of other species of Plectranthus to explain
      their traditional uses.

PMID- 16289603
TI  - Antihypertensive and vasodilator effects of methanolic and aqueous extracts of
      Tribulus terrestris in rats.
AB  - The effects of methanolic and aqueous extracts of Tribulus terrestris on rat
      blood pressure (BP) and the perfused mesenteric vascular bed were investigated.
      The extracts dose-dependently reduced BP in spontaneously hypertensive rats
      (SHRs) with the aqueous fraction being more potent than the methanolic fraction
      at all doses tested. In vitro, the methanolic but not aqueous extract produced a
      dose-dependent increase in perfusion pressure of the mesenteric vascular bed.
      When perfusion pressure was raised with phenylephrine (10(-5) M), the aqueous
      extract produced a dose-dependent reduction in perfusion pressure at all doses. A
      low dose of the methanolic extract produced a vasoconstrictor effect while higher
      doses produced dose-dependent reduction in perfusion pressure. L-NAME (10(-4) M)
      significantly reduced but did not abolish vasodilation induced by the extracts.
      Vasodilator responses to aqueous and methanolic fractions were significantly
      reduced in preparations where perfusion pressure was raised with KCl (60 mM). A
      combination of KCl and L-NAME abolished the vasodilator responses induced by the
      extracts. It was concluded that methanolic and aqueous extracts of Tribulus
      terrestris possess significant antihypertensive activity in spontaneously
      hypertensive rats. The antihypertensive effects appeared to result from a direct
      arterial smooth muscle relaxation possibly involving nitric oxide release and
      membrane hyperpolarization.

PMID- 16289604
TI  - Action of Hygrophila auriculata against streptozotocin-induced oxidative stress.
AB  - Hygrophila auriculata (K. Schum.) Heine (Family: Acanthaceae) is a wild herb
      widely used in 'Ayurveda' as 'Rasayana' drug for treatment of various disorders.
      Treatment of diabetic rats with aerial parts of Hygrophila auriculata extract
      (HAEt, 100 and 250 mg/kg body weight) for 3 weeks showed significant reduction in
      blood glucose, thiobarbituric acid reactive substances (TBARS) and hydroperoxide
      in both liver and kidney. The treatment with HAEt significantly increased the
      glutathione (GSH), glutathione peroxidase (GPx), glutathione S-transferase (GST)
      and catalase (CAT) in the drug-treated group, which is comparable to the control
      group. HAEt and glibenclamide-treated rats also showed decreased lipid
      peroxidation that is associated with increased activity of superoxide dismutase
      (SOD) and catalase. The ability of HAEt on tissue lipid peroxidation and
      antioxidant status in diabetic animals has not been studied before. The result of
      this study thus shows that HAEt possesses significant antidiabetic activity along
      with potent antioxidant potential in diabetic conditions.

PMID- 16289605
TI  - A novel application of multi-wavelength TIRF spectroscopy for real time
      monitoring of antithrombin interactions with immobilized heparin.
AB  - Real time interactions of antithrombin (AT) with Corline Heparin Surfaces (CHS)
      with one and two layers of heparin conjugate have been examined using a multi
      wavelength TIRF spectroscopy technique with continuous flow. Fluorescently
      labeled AT, adsorbed from citrated human blood plasma, showed significantly
      higher signals on CHS compared to the cationic surface used to attach the heparin
      conjugate. The AT binding to CHS was very stable, also after exposure to soluble
      heparin at a concentration of 1.5 IU/mL. Only a few percent of the bound AT were
      displaced from the surfaces by AT present in plasma after long-term exposure to
      plasma. In contrast, larger amounts of the freshly added AT had adsorbed to the
      surfaces, especially to the surface with two layers of heparin conjugate,
      indicating the presence of unsaturated AT binding sites. The amount of AT bound
      to the different surfaces was quantified after elution using an enzyme
      immunoassay (EIA). Characteristic emission spectra of proteins and fluorophores
      of labeled proteins, obtained at the surfaces after a long-term exposure to
      plasma, confirmed their presence at the surfaces. The multi-wavelength TIRF
      technique proved to be a useful tool when combined with other techniques to study
      the time course of interactions of fluorescently labeled proteins with
      biomaterials, even in a complex environment such as plasma.

PMID- 16289606
TI  - Miniaturized immunoassay microfluidic system with electrokinetic control.
AB  - A portable heterogeneous immunoassay system is presented in this paper. It
      consists of a poly(dimethylsiloxane) (PDMS) based microfluidic chip as the
      immunoreactor, a miniaturized programmable high voltage sequencer as the power
      supply and the flow controller, and a laser-optical fiber fluorescence detection
      module as the signal reader. The operation of this immunoassay system is
      automatic. The sequential reagent dispensing and washing processes are controlled
      by the programmable sequencer. The reagent consumption was only 12 microL and the
      assay time was only 26 min. The detection limit for Escherichia coli O157:H7
      bacterial antigen with this miniaturized system was 0.3 ng/muL, lower than that
      obtained using fluorescence microscope in previous studies.

PMID- 16289607
TI  - Micromachined sensor for lactate monitoring in saliva.
AB  - A miniaturised sensor for continuous lactate measurement in saliva was developed
      and tested. The sensor was built using silicon microfabrication technologies. The
      size of the chip is 5.5 mmx6.4 mmx0.7 mm and features a working, a counter and an
      Iridium reference electrode. The chip has a cavity whose floor is perforated by
      fine pores. The cavity contains the enzyme lactate oxidase (LOD), which is
      immobilised in an agarose gel. Prior to the amperometric detection of the
      reaction product hydrogen peroxide at the working electrode, the analyte lactate
      has to pass the pores to reach the cavity with the lactate oxidase by diffusion.
      To test the silicon sensor, capillary blood and saliva samples were obtained
      during standardised ergometer tests. Salivary lactate concentrations were
      determined with the sensor and compared to photometrically derived data from a
      lab-automate. In addition the saliva data were compared to standard capillary
      blood lactate concentrations measured with a pocket photometer. Lactate
      concentration versus load graphs were plotted and compared visually showing very
      similar progressions. The novel approach enables a location independent,
      permanent real-time measurement of the lactate concentration during exercise.

PMID- 16289608
TI  - Automatic and effortful emotional information processing regulates different
      aspects of the stress response.
AB  - There is increasing evidence that stress and self-regulation are important
      factors in the development and treatment of psychopathology. A key issue is to
      determine how cognitive-emotional systems modulate the stress response. We sought
      to determine whether effortful and automatic processing were differentially
      associated with subsequent mood and cortisol levels during a stressful challenge.
      We examined this question by having clinically anxious, depressed, and control
      participants perform a modified spatial cueing task with supraliminal and masked
      pictorial stimuli during a stressful challenge and control condition. The
      stressful challenge, relative to the control condition, lowered mood, but did not
      influence cortisol levels. In the full sample, disengagement from supraliminal
      dysphoric pictures was associated with subsequent mood ratings, whereas
      disengagement from masked pictures depicting threat was associated with
      subsequent cortisol levels. Effortful and automatic processing appears to
      regulate different aspects of the stress response.

PMID- 16289610
TI  - Genome-wide analysis of mammalian DNA segment fusion/fission.
AB  - As a powerful tool for gene function prediction, gene fusion has been widely
      studied in prokaryotes and certain groups of eukaryotes, but it has been little
      applied in studies of mammalian genomes. With the first fully sequenced mammalian
      genomes (human, mouse, rat) now available, we defined and collected a set of
      fusion/fission event-linked segments (FFLS) based on structured organized genomic
      alignment. The statistics of the sequence features highlighted the FFLSs against
      their random context. We found that there are three groups of FFLSs with
      different component pairs (i.e. gene-gene, gene-noncoding and noncoding
      noncoding) in all three mammalian genomes. The proteins encoded by the components
      of FFLSs in the first group shown a strong tendency to interact with each other.
      The segmental components in the last two groups which did not contain any protein
      coding genes, were found not only to be transcribed to some level, but also more
      conserved than the random background. Thus, these segments are possibly carrying
      certain biologically functional elements. We propose that FFLS may be a potential
      tool for prediction and analysis of function and functional interaction of
      genetic elements, including both genes and noncoding elements, in mammalian
      genomes. The full list of the FFLSs in the genomes of the three mammals is
      available as supporting information at doi:10.1016/j.jtbi.2005.09.016.

PMID- 16289609
TI  - Corticostriatal-hypothalamic circuitry and food motivation: integration of
      energy, action and reward.
AB  - Work over the past decade has supported the idea that discrete aspects of
      appetitive motivation are differentially mediated by separate but interacting
      neurochemical systems within the nucleus accumbens (Acb). We review herein a
      series of studies in rats comparing the effects of manipulating Acb amino acid,
      opioid, acetylcholine, and dopamine systems on tests of free-feeding and food
      reinforced operant responding. Results from our laboratory and in the literature
      support three general conclusions: (1) GABA output neurons localized exclusively
      within the Acb shell directly influence hypothalamic effector mechanisms for
      feeding motor patterns, but do not participate in the execution of more complex
      food-seeking strategies; (2) enkephalinergic neurons distributed throughout the
      Acb and caudate-putamen mediate the hedonic impact of palatable (high sugar/fat)
      foods, and these neurons are under modulatory control by striatal cholinergic
      interneurons; and (3) dopamine transmission in the Acb governs general motoric
      and arousal processes related to response selection and invigoration, as well as
      motor learning-related plasticity. These dissociations may reflect the manner in
      which these neurochemical systems differentially access pallido-thalamo-cortical
      loops reaching the voluntary motor system (in the case of opioids and dopamine),
      versus more restricted efferent connections to hypothalamic motor/autonomic
      control columns (in the case of Acb shell GABA and glutamate systems). Moreover,
      we hypothesize that while these systems work in tandem to coordinate the
      anticipatory and consummatory phases of feeding with hypothalamic energy-sensing
      substrates, the striatal opioid network evolved a specialized capacity to promote
      overeating of energy-dense foods beyond acute homeostatic needs, to ensure an
      energy reserve for potential future famine.

PMID- 16289611
TI  - Protein and nucleic acid together: a mechanism for the emergence of biological
      selection.
AB  - The ability of RNA to both replicate and carry out enzymic functions has led to
      the proposal that an 'RNA-world' preceded the emergence of protein function in
      pre-biotic evolution. This order of function requires a key transition in which
      replicating RNA-molecules 'breakout' and recruit protein function. Here I propose
      a mechanism for the co-evolution of protein and nucleic acids as replicating
      entities from the earliest stages of pre-biotic development. In the model,
      amyloid protein fibres provide a protective support and compartment for nucleic
      acids. In turn, replicating nucleic acids stimulate fibre growth at amyloid free
      ends. Nucleic acid-amyloid fibre combinations are proposed to lengthen and then
      break through hydrostatic shear, exposing new amyloid free ends. This process
      would distribute stable replicating complexes throughout the primordial
      environment. The model provides a route into the RNA-protein world without the
      need for a distinct 'breakout' transition.

PMID- 16289612
TI  - Use of hand-held laser scanning in the assessment of craniometry.
AB  - The intra- and inter-examiner reliability was evaluated for hand-held 3D laser
      scanning technology when it was combined with localization of landmarks for
      craniometry. The data from the laser surface scanning were compared with those of
      conventional direct measuring. Using thirty unidentified skulls requested for
      individual identification, measurements were taken of the line distances from
      lambda to 26 landmarks, and also for seven breadth parameters. For the laser
      surface scanning, two examiners performed replicate measurements with an interval
      of 1 week. In the conventional direct measuring, the first examiner took
      replicate measurements with a 1-week interval. To assess intra- and inter
      examiner reliabilities, the intraclass correlation coefficient was used. Analysis
      of variance with repeated measures for each parameter was performed to compare
      the conventional method with the 3D scanning method. Both the 3D scanning and
      conventional methods showed excellent intra-examiner reliabilities, and the 3D
      laser scanning method also showed excellent inter-examiner reliability. A
      statistical difference between the two examiners was found only in nasal breadth
      in the 3D laser scanning method. There was no significant difference between the
      two measuring methods, though the 3D laser scanning method tended to give a
      slightly lower reading. Collectively, the 3D laser scanning method with point
      localization is a useful method with excellent reliability, and it can replace
      the conventional direct measuring method in craniometry.

PMID- 16289613
TI  - Y-chromosome STRs in an Antioquian (Colombia) population sample.
AB  - Haplotype data were obtained from a sample of 777 unrelated male individuals from
      Antioquia Department (Colombia), for eight Y-chromosome STRs (DYS19, DYS385,
      DYS389 I, DYS389 II, DYS390, DYS391, DYS392 and DYS393). A total of 442 different
      haplotypes were identified of which 334 were represented only once in the
      database and the most frequent haplotype was found in 32 individuals. A high
      haplotype diversity was found (99.45%). Genetic distances were calculated using
      previously published haplotype data and the lowest values were found for the
      comparisons with samples of lberian origin.

PMID- 16289614
TI  - Messenger RNA profiling: a novel method for body fluid identification by real
      time PCR.
AB  - Conventional methods for the identification of different body fluids like blood,
      semen and saliva from biological stains involve immunological or enzymatic
      detection of certain proteins. In this study, we investigated potential RNA
      markers with the aim of developing Real-Time polymerase chain reaction (PCR)
      based methods to allow differentiation between several body fluids. Total RNA
      samples from artificially stained swabs and from various pieces of evidence from
      case work were extracted, amplified and analyzed with several RNA markers. Three
      assays detecting the body fluids of interest were selected: hemoglobin-alpha
      locus 1 (HBA), kallikrein 3 (KLK) and mucin 4 (MUC). With this approach, we
      demonstrate that specific Real-Time PCR assays are useful in identifying the
      source of the biological stain. Furthermore, RNA profiling of various body fluids
      was even possible on samples stored over a long period of time at ambient
      temperature. The stability and sensitivity of the applied method outlines a novel
      application for Real-Time PCR within the forensic field.

PMID- 16289615
TI  - Fatal poisoning in Nordic drug addicts in 2002.
AB  - The present study from 2002 includes medicolegally examined fatal poisonings
      among drug addicts in the five Nordic countries: Denmark, Finland, Iceland,
      Norway and Sweden. A common definition "drug addict" is applied by the
      participating countries. The number of deaths, age, sex, place of death, main
      intoxicant and other drugs present in the blood are recorded in order to obtain
      national data, as well as comparable Nordic data and data comparable to earlier
      studies from 1997 and 1991. The Icelandic results are commented on separately due
      to the low number of cases. The most fatal overdoses are seen in Norway, in both
      the death rate (number per 100,000 inhabitants=8.44) and in absolute number
      (n=232). The comparable figures for the other four countries are Denmark 5.43
      (n=175), Iceland 3.6 (n=6), Finland 2.93 (n=94) and Sweden 2.56 (n=136). In
      earlier studies from 1991 and 1997, the highest death rate is seen in Denmark,
      with Norway as number two. Denmark is the only country where the death rate
      decreases from 1997 to 2002. A relatively large increase in deaths in the younger
      age groups (<30 years) is noted from 1997 to 2002, except in Denmark, where only
      a small increase in overdose deaths in very young people (15-19 years) is
      observed. Females account for 12-20% of the overdoses (three out of six deaths in
      Iceland). Relatively fewer deaths are recorded in the capital areas in 2002 than
      in 1997 and 1991, suggesting more geographically widespread drug use in the
      Nordic countries. Heroin/morphine is the single most frequently encountered main
      intoxicant, varying from 10% of the cases in Finland to 72% of the cases in
      Norway. Finland differs from the other countries in that a high percentage of the
      fatal overdoses in Finland are not caused by an illicit drug; buprenorphine
      overdoses are seen, and relatively few deaths resulting from heroin are seen.
      Methadone is the main intoxicant in 41% of the Danish overdose cases, 15% of the
      Norwegian cases, 4% of the Swedish cases and none of the Finnish overdose cases,
      an observation probably linked to different national prescription rules for
      methadone. The analytical screening reveals extended polydrug use. Frequently
      seen substances, in addition to the main intoxicant are amphetamine,
      tetrahydrocannabinol (THC), benzodiazepines and ethanol.

PMID- 16289616
TI  - Distinct mRNA, protein expression patterns and distribution of oestrogen
      receptors alpha and beta in human primary breast cancer: correlation with
      proliferation marker Ki-67 and clinicopathological factors.
AB  - To elucidate the molecular profile of oestrogen receptors alpha and beta
      (ERalpha, ERbeta) we studied ERalpha and ERbeta expression at the mRNA and
      protein levels using real-time polymerase chain reaction (RT-PCR), Western blot
      analysis and immunohistochemical (IHC) methods in 41 primary breast cancers and
      surrounding tissues. ERalpha mRNA and ERbeta mRNA were detected in all of the
      breast cancer and normal matched tissues analysed. ERalpha mRNA levels showed
      greater diversity than ERbeta mRNA levels and the range of amount of ERbeta
      transcripts was far smaller than that of ERalpha. At the protein level, the
      percentage of ERalpha- or ERbeta-positive cases changed. Seventy percent of the
      tumours studied produced full-length 65 kDa ERalpha protein in Western blot
      analysis and 67% of assessed cases were positive in IHC. Full-length 57 kDa
      ERbeta protein was detected by Western blotting in 97% of analysed breast
      cancers, while 67% were ERbeta-positive using IHC. ERalpha was localised in the
      nucleus, while cytoplasmic and perinuclear localisation of ERbeta was observed in
      normal as well as in breast cancer cells. The amount of ERalpha (but not ERbeta)
      increased with age. The expression of ERalpha correlated positively with
      progesterone receptor and negatively with proliferation marker Ki-67. These
      results confirm the previous observations that the lack of ERalpha protein
      expression is not due to lack of ERalpha gene expression or methylation of
      ERalpha promoter, but due to post-transcriptional or post-translational
      mechanisms. Our investigation also suggests that ERalpha is more dysregulated in
      breast cancer, and thereby ERbeta is more tightly regulated in the tumour.

PMID- 16289617
TI  - Differential sensitivity of liposarcoma subtypes to chemotherapy.
AB  - Liposarcoma is one of the most common soft tissue sarcomas and has a number of
      different subtypes: well-differentiated; dedifferentiated; myxoid/round cell; and
      pleomorphic. However, the response of these subgroups to chemotherapy is not well
      documented. In this study, we have conducted a retrospective analysis of a
      prospectively maintained database of soft tissue sarcoma patients treated at the
      Royal Marsden Hospital. Eighty-eight liposarcoma patients who received
      chemotherapy between August 1989 and June 2004 were identified. The response
      rates to chemotherapy of the different histological subtypes and overall and
      progression free survival were investigated. Survival according to histological
      grade was also assessed. A statistically significant higher response rate to
      first-line chemotherapy was observed in patients with myxoid liposarcoma compared
      to de- and well-differentiated tumours, 48% (95%CI; 28-69) and 11% (95%CI; 2-29),
      P = 0.005. Similarly, those with myxoid liposarcoma had a significantly higher
      response rate compared to all other liposarcoma patients, 48% (95%CI; 28-69) and
      18% (95%CI; 8-31). Patients with lower grade tumours had better overall survival.
      This retrospective analysis suggests that myxoid liposarcoma is relatively
      chemosensitive in comparison to a combination of other liposarcomas, and in
      particular de- and well-differentiated tumours. Further confirmation of these
      results should be sought by similar analyses of other databases.

PMID- 16289618
TI  - Exfoliated buccal and microdissected lung cell expression of antioxidant enzymes.
AB  - INTRODUCTION: An exfoliated buccal cell biomarker assay for antioxidant gene
      transcript levels was used to measure inter-tissue concordance with lung, and
      inter-subject variability in a lung cancer case-control study. METHODS: First,
      qualitative RNA-specific RT-PCR was used to compare expression in exfoliated
      buccal cells with that in laser microdissected lung tissue remote from the tumor
      from 14 individuals providing both specimens. RESULTS: There was complete [100%
      for quinone oxidoreductase 1 (NQO1), glutathione peroxidase (GPX), and superoxide
      dismutase 1 (SOD1)], or predominant [85.7% for catalase (CAT)] inter-tissue
      concordance for qualitative expression. Second, quantitative real-time RT-PCR for
      antioxidant enzyme transcript levels was performed in exfoliated buccal samples
      from these same 14 individuals, as well as 28 additional individuals providing
      buccal cells only, for a total of 42 buccal specimens (19 current smokers and 23
      ex- or never-smokers), of whom 26 (61.39%) had a new diagnosis of lung cancer.
      DISCUSSION: Wide inter-individual expression differences for each gene transcript
      (>10(1)-10(4)-fold) were observed in the exfoliated buccal cells, unrelated to
      smoking and case-control status. In multivariate analyses, family history of
      tobacco-related malignancy correlated inversely with buccal NQO1 and CAT mRNA
      levels (p=0.003, p<0.001, respectively). This antioxidant expression trait may
      relate to family risk of cancer, but is notably unrelated to oxidant challenges
      inherent in cigarette smoke.

PMID- 16289619
TI  - Bradykinin B2 receptors mediate pulmonary sympathetic afferents induced reflexes
      in rabbits.
AB  - Endogenous bradykinin (BK) is an established mediator of pulmonary inflammation,
      yet its role in lung disease is unclear. In the rabbit, injecting BK into the
      lung parenchyma elicits reflex hyperpnea, tachypnea, hypotension, and bradycardia
      by stimulating pulmonary sympathetic afferents. To further explore bradykinin
      effects, breathing pattern (phrenic nerve and abdominal muscle activities) and
      hemodynamics (blood pressure and heart rate) were examined in anesthetized, open
      chest, and mechanically ventilated rabbits. Three receptor agonists [bradykinin,
      selective B(1) (des-Arg(9)-BK), and selective B(2) (Tyr(8)-BK)], as well as three
      B(2) receptor antagonists, B6029 (N alpha-Adamantaneacetyl)-Bradykinin, B(1)650
      (D-Arg-[Hyp(3), Thi(5,8), D-Phe(7)]-Bradykinin, or Hoe-140 (D-Arg-[Hyp(3),
      Thi(5), D-Tic(7), Oic(8)] bradykinin), were used to identify the responsible
      receptor subtype. In both intact and vagotomized rabbits, injecting BK or a
      selective B(2) agonist into the lung elicited similar cardiopulmonary responses.
      These reflex responses were greatly attenuated or blocked by pre-injecting B(2)
      antagonists into the right atrium or into the lung parenchyma. In contrast, the
      B(1) agonist elicited fewer cardiopulmonary effects in intact rabbits and had no
      effect in vagotomized rabbits. We conclude that BK stimulates pulmonary
      sympathetic afferents [Soukhova, G., Wang, Y., Ahmed, M., Walker, J., Yu, J.,
      2003. Bradykinin stimulates respiratory drive by activating pulmonary sympathetic
      afferents in the rabbit. J. Appl. Physiol. 95, 241-249.; Wang, Y., Soukhova, G.,
      Proctor, M., Walker, J., Yu, J., 2003. Bradykinin causes hypotension by
      activating pulmonary sympathetic afferents in the rabbit. J. Appl. Physiol. 95,
      233-240.], eliciting a characteristic cardiopulmonary reflex via B(2) receptors.

PMID- 16289620
TI  - Lipopolysaccharide stimulates the production of prostaglandin E2 and the receptor
      Ep4 in osteoblasts.
AB  - Previous studies have indicated that one of the causes of alveolar bone
      destruction with periodontitis is lipopolysaccharide (LPS) from the cell wall of
      gram-negative bacteria in plaque, and that prostaglandin E(2) (PGE(2)) is one of
      the bone resorption factors that stimulate osteoclast formation through an
      intercellular interaction between osteoblasts and osteoclast precursors. The
      present study was undertaken to determine the effect of LPS on cell growth,
      alkaline phosphatase (ALPase) activity, the production of PGE(2), and the
      expression of receptors by PGE(2), cyclooxygenase (COX)-1, and COX-2, using human
      osteosarcoma cell line Saos-2 as osteoblasts. The cells were cultured with 0, 1,
      or 10 microg mL(-1) of LPS for up to 14 days. The production of PGE(2) and the
      gene expression of COX-1, COX-2, and PGE(2) receptors, including Ep1, Ep2, Ep3,
      and Ep4, were determined using enzyme-linked immunosorbent assay (ELISA) and real
      time reverse transcription-polymerase chain reaction (real-time RT-PCR),
      respectively. With the addition of LPS, cell growth and ALPase activity decreased
      by day 5 of the culture, while PGE(2) production increased in a dose-dependent
      manner throughout the entire 14-day culture period. LPS-reduced ALP activity and
      LPS-induced PGE(2) production returned to the control level by the addition
      simultaneously with indomethacin. The expression of COX-1, Ep1, Ep2, and Ep3
      receptors decreased on day 14 of the culture, whereas the expression of COX-2 and
      Ep4 receptors increased significantly with the addition of LPS. These results
      suggest that LPS promotes PGE(2) production by increasing the expression of COX
      2, and that LPS promotes the production of Ep4 receptors in osteoblasts. These
      results also indicate that LPS-induced PGE(2) may combine with osteoblast Ep4
      receptors in autocrine or paracrine modes, and may promote the formation of
      osteoclasts.

PMID- 16289621
TI  - Comparison of opioid receptor distributions in the rat ileum.
AB  - The cellular expression patterns of mu-, delta- and kappa-opioid receptors in the
      rat ileum were examined using fluorescence immunohistochemistry. Double-labelling
      was used to examine cellular receptor co-localisation as a pre-requisite for
      intracellular molecular interactions, such as heterodimerisation. Tissues were
      stained as whole-mount preparations. Strong, broadly distributed immunoreactivity
      (ir) was observed for each receptor in the myenteric and submucous plexuses.
      Although intracellular mu- and delta-ir patterns differed in ganglion neurons,
      mu/delta co-expression was extensive in these cells. mu/delta co-expression was
      also observed in interstitial cells, which were diffusely distributed in
      submucous plexus preparations but generally located adjacent to myenteric plexus
      structures. Punctate kappa-ir was seen broadly in nerve fibres in both plexuses,
      suggesting localisation in varicosities. Neuronal mu/kappa co-localisation was
      not apparent, although kappa-ir fibres were often apposed against mu-ir cells.
      mu/kappa co-localisation was detected in interstitial cells in submucous plexus
      preparations. Similarities in mu and delta expression patterns might reflect
      similar functional properties previously detected for these receptors. This study
      indicates that the rat gastrointestinal tract might provide a useful tool for the
      future study of molecular interactions between opioid receptor types.

PMID- 16289622
TI  - Water soluble feruloyl arabinoxylans from rice and ragi: changes upon malting and
      their consequence on antioxidant activity.
AB  - The objective of this study is to determine the changes brought about by
      germination on water soluble feruloyl arabinoxylans (feraxans), one of the major
      components of soluble fibre from rice and ragi and their consequence on
      antioxidant activity. Soluble feraxans, isolated from native and malted rice and
      ragi were fractionated on DEAE-cellulose. Ferulic acid content of the major [0.1
      molar ammonium carbonate (AC) eluted] fraction was higher in malts (rice: 1045
      microg/g; ragi: 1404 microg/g) than in native (rice: 119 microg/g; ragi: 147
      microg/g) and this fraction was separated by Sephacryl S-300 chromatography into
      two peaks each in rice (native: 232 and 24.4 kDa; malt: 75.4 and 39.6 kDa) and
      ragi (native: 140 and 15.4 kDa; malt: 38.9 and 15.4 kDa). 0.1 molar AC eluted
      fractions showed very strong antioxidant activity in vitro as determined by beta
      carotene-linoleate emulsion (IC50: 0.16-0.24 mg), DPPH* (IC50: 4.1-11.4 mg) and
      Ferric reducing/antioxidant power, FRAP (EC1: 0.76-3.1mg) assays. Antioxidant
      activity of feraxans was several (4.9-1400) folds higher than the expected
      activity due to their bound ferulic acid content. Apart from ferulic acid,
      presence of sugars with >C=O (uronyl/acetyl) groups and degree/nature of glycan
      polymerization were observed to influence antioxidant activity of the
      polysaccharides. Malting resulted in many dynamic changes in the ferulic acid
      content in different feraxan types and affected their antioxidant activity.

PMID- 16289624
TI  - Removal of H(2)S by Thiobacillus denitrificans immobilized on different matrices.
AB  - Biological removal of high concentrations of H(2)S was studied using the
      immobilized Thiobacillus denitrificans with peat moss, wood chip, ceramic and
      granular activated carbon (GAC) separately. Experiments on the physical
      adsorption capacity of matrix, retention time and pressure drop were carried out;
      the ability of bioreactor to buffer shock loading and the removal efficiency with
      different packing materials were also investigated. Besides, the kinetics of
      single-stage biodesulfuration was analyzed. The results showed that GAC provided
      higher bacteria adsorption capacity, showed a more resistance to shock loading
      and allowed better operational control with respect to pressure drop than other
      inert carriers. When the retention time was changed from 30 to 100 s at an
      influent concentration of 100 mg/L of H(2)S, the removal efficiencies were above
      98%; when the inlet concentration of H(2)S were changed from 110 to 120 mg/L, an
      average 96.8% removal efficiency was achieved during the long-term operation for
      GAC bioreactor. Next to GAC, wood chip was found to be a good packing material;
      however, peat moss and ceramic had limited effectiveness and their removal
      efficiencies were less of 90%. The kinetic analysis showed that the maximum
      removal rate and the half-saturation constant of the GAC bioreactor were 666.7 mg
      (H(2)S)/(L.d) and 20.8 mg/L, respectively.

PMID- 16289623
TI  - Simple assessment of homogeneity in pharmaceutical mixing processes using a near
      infrared reflectance probe and control charts.
AB  - Determination of homogeneous mixing of the active pharmaceutical ingredient (API)
      is an important in-process control within the manufacturing of solid dosage
      forms. In this paper two new near-infrared (NIR) based methods were presented; a
      qualitative and a quantitative method. Both methods are based on the calculation
      of net analyte signal (NAS) models which were very easy to develop, specific with
      respect to the API and required no additional reference analysis. Using a well
      mixed batch as a 'golden standard' batch, control charts were developed and used
      for monitoring the homogeneity of other batches with NIR. The methods were fast,
      easy to use, non-destructive and provided statistical tests of homogeneity. A
      mixing study was characterized with the two methods and the methods were
      validated by comparison with traditional HPLC analysis.

PMID- 16289625
TI  - Estimation of maturity of compost from food wastes and agro-residues by multiple
      regression analysis.
AB  - The composting process of food wastes and tree cuttings was examined on four
      composting types composed from two kinds of systems and added mixture of
      microorganisms. The time courses of 32 parameters in each composting type were
      observed. The efficient composting system was found to be the static aerated
      reactor system in comparison with the turning pile one. Using the multiple
      regression analysis of all the data (159 samples) obtained from this study, some
      parameters were selected to predict the germination index (GI) value, which was
      adopted as a marker of compost maturity. For example, using the regression model
      generated from pH, NH(4)(+) concentration, acid phosphatase activity, and
      esterase activity of water extracts of the compost, GI value was expressed by the
      multi-linear regression equation (p<0.0001). High correlations between the
      measured GI value and the predicted one were made in each type of compost. As a
      result of these observations, the compost maturity might be predicted by only
      sensing of the water extract at the composting site without any requirements for
      a large-size equipment and skill, and this prediction system could contribute to
      the production of a stable compost in wide-spread use for the recycling market.

PMID- 16289626
TI  - Calcium carbonate formation by Synechococcus sp. strain PCC 8806 and
      Synechococcus sp. strain PCC 8807.
AB  - Precipitation of CaCO3 catalyzed by the growth and physiology of cyanobacteria in
      the genus Synechococcus represents a potential mechanism for sequestration of
      atmospheric CO2 produced during the burning of coal for power generation.
      Synechococcus sp. strain PCC 8806 and Synechococcus sp. strain PCC 8807 were
      tested in microcosm experiments for their ability to calcify when exposed to a
      fixed calcium concentration of 3.4 mM and dissolved inorganic carbon
      concentrations of 0.5, 1.25 and 2.5 mM. Synechococcus sp. strain PCC 8806 removed
      calcium continuously over the duration of the experiment producing approximately
      18.6 mg of solid phase calcium. Calcium removal occurred over a two-day time
      period when Synechococcus sp. strain PCC 8807 was tested and only 8.9 mg of solid
      phase calcium was produced. Creation of an alkaline growth environment catalyzed
      by the physiology of the cyanobacteria appeared to be the primary factor
      responsible for CaCO3 precipitation in these experiments.

PMID- 16289627
TI  - Chemical and physical properties of pruning waste compost and their seasonal
      variability.
AB  - Selected chemical and physical properties of 12 different pruning waste compost
      (PWC) samples were evaluated to assess their suitability as substrates for
      ornamental plants. Samples were taken periodically from the same composting
      facility over 18 months in order to determine if there was any seasonal
      variability. In addition to the PWC samples, a Canadian Sphagnum peat and a
      commercial growing medium (CGM) were used as standard materials. With respect to
      PWC properties, pH values were above 8, significantly higher than the pH of peat
      and the commercial substrate. All samples showed adequate levels of organic
      matter and correspondingly high cation-exchange capacity (CEC) values. The C/N
      ratio varied between 22 and 48, significantly higher than the optimal values of
      15-20. Although composts were sampled from piles established in different
      seasons, no significant differences were found in their chemical properties.
      However, water retention characteristics were affected by seasonal changes in
      components entering the facility. Comparing the properties of PWC to those of
      peat and commercial growing medium, this material appears to be an acceptable
      component of a substrate for container-grown ornamental plants.

PMID- 16289628
TI  - Cloning and characterization of wheat PDI (protein disulfide isomerase)
      homoeologous genes and promoter sequences.
AB  - The genomic and cDNA sequences of three PDI homoeologous genes located on
      chromosomes 4A, 4B and 4D of bread wheat and their promoters were cloned and
      sequenced. The three sequences showed a very high conservation of the coding
      region and of the exon/intron structure, which consisted of ten exons. The
      comparison of wheat sequences with those of rice and Arabidopsis showed a
      significant conservation of the exon/intron structure across the three species.
      The expression of each gene was analysed by RT-PCR in different plant tissues
      (roots, coleoptiles, spikelets, leaves and developing caryopses). All the genes
      showed a higher expression in developing caryopses than in other analysed
      tissues, wherein some differences were detected. The promoter sequences of the
      three genes possessed some regulatory motifs typical of endosperm specific
      expression.

PMID- 16289629
TI  - Acetylation and deacetylation of non-histone proteins.
AB  - Since the first report of p53 as a non-histone target of a histone
      acetyltransferase (HAT), there has been a rapid proliferation in the description
      of new non-histone targets of HATs. Of these, transcription factors comprise the
      largest class of new targets. The substrates for HATs extend to cytoskeletal
      proteins, molecular chaperones and nuclear import factors. Deacetylation of these
      non-histone proteins by histone deacetylases (HDACs) opens yet another exciting
      new field of discovery in the role of the dynamic acetylation and deacetylation
      on cellular function. This review will focus on these non-histone targets of HATs
      and HDACs and the consequences of their modification.

PMID- 16289630
TI  - Use of a restriction endonuclease cytotoxicity assay to identify inducible GAL1
      promoter variants with reduced basal activity.
AB  - Inducible promoter fusions are commonly employed to study the biological
      functions of genes as well as to investigate mechanisms of transcription
      regulation. A concern for many studies of heterologous gene expression is that
      steady state transcription may be too high under non-inducing conditions,
      producing undesired phenotypes prior to induction. Fusions containing the
      galactose-inducible GAL1 promoter joined to PvuII, a bacterial DNA endonuclease
      gene, are toxic to yeast cells even under non-inducing conditions, i.e., in
      glucose media. This toxicity was utilized in conjunction with PCR-based
      mutagenesis of the GAL1 regulatory region to isolate mutant promoters that
      retained high inducibility but exhibited reduced basal level expression. The Mig1
      repressor binding and putative TATA box regions were unchanged among four mutant
      promoters examined in detail. However, each promoter contained one or more
      mutations within previously identified binding sites for the Gal4 activator
      protein. Genetic assays developed to monitor GAL1p::I-SceI endonuclease-induced
      recombination demonstrated that basal expression from two of the new promoters
      (designated GAL1-V4 and GAL1-V10) was strongly reduced. These experiments and
      additional quantitative luciferase reporter gene assays demonstrate the utility
      of the approach for identifying promoters that permit more tightly controlled
      gene expression.

PMID- 16289631
TI  - Examples of tropical disease control in the humanitarian medical programmes of
      MSF and Merlin.
AB  - Humanitarian medical programmes in the tropics have the opportunity to provide
      beacons of good practice. The use of modern drugs and diagnostics, a lack of
      bureaucracy, adequate budgets, motivated staff and well-functioning supply lines
      all contribute to the success of this approach. At a joint meeting of the Royal
      Society of Tropical Medicine, the London School of Hygiene and Tropical Medicine,
      Medecins Sans Frontieres and Merlin, new data were presented on the outcomes of
      recent humanitarian programmes to control malaria (Ethiopia), human African
      trypanosomiasis (south Sudan), Lassa fever (Sierra Leone) and tuberculosis
      (Tomsk, former USSR).

PMID- 16289632
TI  - Use of the Dermatology Life Quality Index in filarial lymphoedema patients.
AB  - The global programme to eliminate lymphatic filariasis has alleviation of
      suffering and disability as one of its components, and many efforts are being
      taken across the globe in this direction. However, there is no effective tool to
      assess the impact of these efforts on patients' quality of life and/or lessening
      of disability and suffering. The present paper reports the use of the Dermatology
      Life Quality Index (DLQI) in filarial lymphoedema patients. DLQI scores were
      collected from 203 patients recruited from a clinic and from the community. The
      DLQI score ranged from 0 to 17, and a mean score of 2.7 (SD 4.4) or 9.0%
      disability. This score is lower than many skin diseases reported so far. The
      scores for individual questions vary, but the degree of consistency of responses
      between questions is high. The differences between sexes, place of recruitment
      and grades of lymphoedema are not significant. Although the DLQI measures the
      quality of life due to lymphoedema, this study further warrants development of a
      good quality-of-life index for lymphoedema patients.

PMID- 16289633
TI  - The N-terminus of the norepinephrine transporter regulates the magnitude and
      selectivity of the transporter-associated leak current.
AB  - The norepinephrine (NE) transporter (NET) mediates the removal of NE from
      synaptic spaces and is a major target for antidepressants, amphetamine and
      cocaine. Previously, we have shown that syntaxin 1A (SYN 1A) supports human NET
      (hNET) cell surface expression, that hNET/SYN 1A interactions are direct and
      mediated by the hNET N-terminus, and that the hNET/SYN 1A association limits
      substrate-induced hNET-associated currents [Sung, U., Apparsundaram, S., Galli,
      A., Kahlig, K.M., Savchenko, V., Schroeter, S., Quick, M.W., Blakely, R.D., 2003.
      A regulated interaction of syntaxin 1A with the antidepressant-sensitive
      norepinephrine transporter establishes catecholamine clearance capacity. J.
      Neurosci. 23, 1697-1709]. These data raise the possibility that the hNET N
      terminus, and potentially its interaction with SYN 1A, might regulate other hNET
      conductance states, including the hNET-mediated leak current. Importantly for
      monoamine transporters, the leak conductance has been shown to play a critical
      role in regulating cell membrane potential and possibly neuronal excitability
      [Quick, M.W., 2003. Regulating the conducting states of a mammalian serotonin
      transporter. Neuron 40, 537-549]. Here we demonstrate that deletion of the
      binding domain for SYN 1A in the NET N-terminus robustly enhances the NET
      mediated leak current as well as its selectivity for Cl- permeation under
      particular intracellular ionic compositions. In addition, we show that the NET N
      terminus coordinates the ability of intracellular Na+ and Cl- to regulate the
      leak conductance. These data suggest that the NET N-terminus regulates and
      defines the ionic specificity of the NET-mediated leak current.

PMID- 16289634
TI  - Down-regulation of GFRalpha-1 expression by antisense oligodeoxynucleotide
      aggravates thermal hyperalgesia in a rat model of neuropathic pain.
AB  - Glial cell line-derived neurotrophic factor (GDNF) has been hypothesized to play
      an important role in the modulation of nociceptive signals especially during
      neuropathic pain. The present study examined the expression of GDNF and GFRalpha
      1 (the high-affinity receptor of GDNF) in dorsal root ganglions (DRG) in a rat
      model of neuropathic pain induced by chronic constriction injury (CCI) to the
      sciatic nerve. In order to address the role of GDNF and GFRalpha-1 in neuropathic
      pain, antisense oligodeoxynucleotide (ODN) specifically against GFRalpha-1 was
      intrathecally administered to result in down-regulation of GFRalpha-1 expression.
      The results showed that both the protein and mRNA levels of GDNF and GFRalpha-1
      were significantly increased after CCI, while the thermal hyperalgesia of
      neuropathic pain rats could be significantly aggravated by antisense ODN
      treatment, but not by normal saline (NS) or mismatch ODN treatment. The present
      study demonstrated that endogenous GDNF and GFRalpha-1 might play an anti
      hyperalgesic role in neuropathic pain of rats. In addition, we found a down
      regulation of somatostatin (SOM) in DRG and spinal dorsal horn after expression
      of GFRalpha-1 was knocked down, which suggested the possible relationship between
      the anti-hyperalgesic effect of GDNF and GFRalpha-1 on neuropathic pain and
      endogenous SOM.

PMID- 16289635
TI  - A modified automated high-throughput mycobacterial interspersed repetitive unit
      method for genotyping Mycobacterium tuberculosis.
AB  - A total of 502 isolates of Mycobacterium tuberculosis collected in Taiwan were
      genotyped using a modified and high-throughput typing system involving
      mycobacterial interspersed repetitive units. The Hunter-Gaston discriminatory
      index improved significantly to 0.972 with the modified 15-locus scheme,
      including ETR-A, ETR-B, and ETR-C, compared with 0.951 for the previously
      reported 12-locus design.

PMID- 16289636
TI  - Single-site chemical modification at C10 of the baccatin III core of paclitaxel
      and Taxol C reduces P-glycoprotein interactions in bovine brain microvessel
      endothelial cells.
AB  - A single-site modification of paclitaxel analogs at the C10 position on the
      baccatin III core that reduces interaction with P-glycoprotein in bovine brain
      microvessel endothelial cells is described. Modification and derivatization of
      the C10 position were carried out using a substrate controlled hydride addition
      to a key C9 and C10 diketone intermediate. The analogs were tested for tubulin
      assembly and cytotoxicity, and were shown to retain potency similar to
      paclitaxel. P-glycoprotein interaction was examined using a rhodamine assay and
      it was found that simple hydrolysis or epimerization of the C10 acetate of
      paclitaxel and Taxol C can reduce interaction with the P-glycoprotein transporter
      that may allow for increased permeation of taxanes into the brain.

PMID- 16289637
TI  - Progestin, estrogen and androgen G-protein coupled receptors in fish gonads.
AB  - The identities of the membrane receptors mediating the majority of rapid, cell
      surface-initiated, nongenomic (i.e. nonclassical) steroid actions described to
      date are unclear. Two novel 7-transmembrane spanning proteins, representing two
      distinct classes of steroid membrane receptors, membrane progestin receptor alpha
      (mPRalpha) and a membrane estrogen receptor (mER), GPR30, have recently been
      identified in several vertebrate species. Evidence that both receptors activate G
      proteins and function as G-protein coupled receptors (GPCRs) is briefly reviewed.
      New data on progestin actions on fish gametes suggest a widespread involvement of
      mPRalpha in oocyte maturation and sperm hyperactivity in this vertebrate group.
      Information on the second messenger pathways activated upon estrogen binding to a
      membrane estrogen receptor in croaker gonads and preliminary evidence for the
      presence of a GPR30-like protein in fish gonads are discussed. Finally, initial
      characterization of the ligand binding, G-protein activation and molecular size
      of a membrane androgen receptor (mAR) in croaker ovaries suggests the presence of
      a third unique steroid receptor in fish gonads that also may function as a GPCR.

PMID- 16289638
TI  - Molecular epidemiology of Campylobacter fetus subsp. fetus on bovine artificial
      insemination stations using pulsed field gel electrophoresis.
AB  - The presence of Campylobacter fetus subspecies fetus (Cff) on bovine artificial
      insemination (AI)-stations can have major economical consequences. More knowledge
      on the epidemiology of C. fetus is needed to control Cff infections at AI
      stations. We assessed the epidemiology of Cff on AI-stations and the molecular
      relationship between Cff strains isolated from outbreaks on AI-stations. Thirteen
      Cff strains (two Cff strains per outbreak and one sporadic case) isolated from
      bulls housed on different AI-stations were selected and compared with ten
      unrelated bovine and ovine Cff isolates from different geographical regions.
      Molecular typing by pulsed field gel electrophoresis (PFGE) with the restriction
      enzymes SmaI, SalI and KpnI, yielded unique profiles for most unrelated strains
      but indistinguishable profiles for all isolates from the same outbreak. Computer
      aided analysis using a composite data set of SmaI, SalI and KpnI restriction
      profiles revealed separate clusters for outbreak strains. Thus, PFGE profiling of
      Cff strains is a valuable tool to discriminate between strains derived from
      separate outbreaks and to identify routes of infection.

PMID- 16289639
TI  - Live attenuated vaccine-based control of necrotic enteritis of broiler chickens.
AB  - A vaccine for necrotic enteritis (NE) of chickens would reduce the current need
      to prevent or treat the disease in broiler chickens with antimicrobial drugs. The
      objective of this study was to understand aspects of immunity to the disease. The
      first experiment examined the virulence of six strains of Clostridium perfringens
      isolated from cases of NE in broiler chickens. Using a 5-day experimental oral
      infection of 2-week-old broiler chickens, four of the six strains were found to
      be virulent. Pulsed-field gel electrophoresis and PCR showed that virulence was
      not associated with a plasmid encoding the beta2 toxin gene, cpb2, since this was
      present in virulent and one of the two avirulent strains. In the second
      experiment, two virulent and one avirulent strains were tested for their ability
      to immunize ("infection-immunization") chickens through the oral route. The
      procedure used experimental infection for 5 days followed by bacitracin treatment
      for 9 days, and then re-challenge 2 days later with a virulent strain, CP4.
      Infection-immunization with the virulent isolates protected chickens from
      subsequent virulent challenge, whereas the infection-immunization with the
      avirulent isolate did not. In a third experiment, two of four alpha-toxin
      negative mutants of CP4 protected birds from experimental NE after oral
      immunization. These two mutants were also attenuated for virulence. We conclude
      that it is possible to immunize chickens successfully against NE and that
      immunogen(s) other than alpha-toxin are important in protective immunity against
      oral infection.

PMID- 16289640
TI  - Postnatal development of cholinergic neurons in the mesopontine tegmentum
      revealed by histochemistry.
AB  - Cholinergic neurons in the laterodorsal tegmental nucleus (LDT) and
      pedunculopontine tegmental nucleus (PPT) play a role in the regulation of several
      kinds of behavior. Some of them, such as locomotion, motor inhibition or sleep,
      show dramatic changes at a certain period of postnatal development. To understand
      the neural substrate for the development of these physiological functions, we
      studied the development of cholinergic neurons in the LDT and PPT of postnatal
      and adult rats using histochemical staining of NADPH-diaphorase (NADPH-d) and
      immunohistochemical staining of choline acetyltransferase (ChAT) and the
      vesicular acetylcholine transporter (VAChT). At postnatal day 1 (P1), ChAT- and
      VAChT-stained cells localized more dorsally than those of NADPH-d-stained cells,
      and at P7 their distributions became similar to those of NADPH-d-stained cells.
      The number of NADPH-d-stained cells increased rapidly after birth, reaching the
      adult level by P7. In contrast, the number of ChAT- and VAChT-stained cells and
      the intensity of their staining decreased from P1 to P3 and then increased
      through P21. The volume of the LDT increased during the second postnatal week.
      These findings indicate that cholinergic neurons in the LDT develop their
      cholinergic properties during the second postnatal week and mature functionally
      thereafter. We discuss these results in light of the several physiological
      functions regulated by the cholinergic neurons in the mesopontine tegmentum.

PMID- 16289641
TI  - Shape configuration and category-specificity.
AB  - We examined the neural correlates of visual shape configuration, the binding of
      local shape characteristics into wholistic object descriptions, by comparing the
      regional cerebral blood flow associated with recognition of outline drawings and
      fragmented drawings. We found no areas that responded more to fragmented drawings
      than to outline drawings even though fragmentation had a clear impact on
      recognition performance. Instead, a region extending from the inferior occipital
      gyri to the middle parts of the fusiform gyri was activated during shape
      configuration of both outline drawings and fragmented drawings. We also examined
      whether fragmentation had different impact on the recognition of natural objects
      and artefacts and found that recognition of artefacts was more affected by
      fragmentation than recognition of natural objects. Thus, the usual finding of an
      advantage for artefacts in difficult object decision tasks, which is also found
      in the present experiments with outlines, is reversed when the stimuli are
      fragmented. This interaction between category (natural versus artefacts) and
      stimulus type (outlines versus fragmented forms) is in accordance with
      predictions derived from a recent account of category-specificity and lends
      support to the notion that category-specific impairments can occur for both
      natural objects and artefacts following damage to pre-semantic stages in visual
      object recognition. The implications of the present findings are discussed in
      relation to theories of perceptual organization, visual object recognition and
      category-specificity.

PMID- 16289643
TI  - Characterization of the venom from the Brazilian Brown Spider Loxosceles similis
      Moenkhaus, 1898 (Araneae, Sicariidae).
AB  - Accidents caused by brown spiders (Loxosceles genus) are frequent in Brazil and
      are associated with dermonecrotic lesions and, eventually, systemic reactions
      that may be lethal. The major species implicated with human envenoming have been:
      L. intermedia, L. gaucho and L. laeta. In this study we characterized the venom
      from Loxosceles similis, a species of spider normally found inside caves. L.
      similis venom was characterized by two-dimensional gel electrophoresis and
      enzymatic activity (dermonecrosis and haemolysis). The lethal dose to mice and
      the capacity of commercial anti-serum to neutralize this venom were also
      analysed. The cross-reactivity with anti-venoms against L. intermedia, L. laeta
      and L. gaucho were studied. Our results showed that this venom was able to induce
      severe dermonecrotic lesions and showed the presence of the bacteria Clostridium
      septicum in association with the fangs. In addition, we have cloned the DNA
      coding for a dermonecrotic protein (LsD1), using the genomic DNA of L. similis.
      The deduced amino acid sequence showed a toxin of approximately 31.2 kDa with an
      estimated pI of 7.37 and sequence similar to LiD1, a protein from the
      dermonecrotic family of Loxosceles intermedia spider venom, a synanthropic
      species of medical importance.

PMID- 16289642
TI  - Identification of novel argonaute-associated proteins.
AB  - RNA silencing processes are guided by small RNAs known as siRNAs and microRNAs
      (miRNAs) . They reside in ribonucleoprotein complexes, which guide the cleavage
      of complementary mRNAs or affect stability and translation of partial
      complementary mRNAs . Argonaute (Ago) proteins are at the heart of silencing
      effector complexes and bind the single-stranded siRNA and miRNA . Our biochemical
      analysis revealed that Ago2 is present in a pre-miRNA processing complex that is
      able to transfer the miRNA into a target-mRNA cleaving complex. To gain insight
      into the function and composition of RNA silencing complexes, we purified Ago1-
      and Ago2-containing complexes from human cells. Several known Ago1- and/or Ago2
      associated proteins including Dicer were identified, but also two novel factors,
      the putative RNA helicase MOV10, and the RNA recognition motif (RRM)-containing
      protein TNRC6B/KIAA1093. The new proteins localize, similar to Ago proteins, to
      mRNA-degrading cytoplasmic P bodies, and they are functionally required to
      mediate miRNA-guided mRNA cleavage.

PMID- 16289644
TI  - Prediction and prevention of preeclampsia and IUGR.
AB  - Preeclampsia, being one of the leading causes of maternal and perinatal morbidity
      and mortality, has been the subject of extensive research since its description.
      Preeclampsia has been called the disease of theories due to the enigma
      surrounding its exact pathophysiology. Despite the absence of treatment that
      reverses the disease process once started, screening for preeclampsia and
      intrauterine growth restriction (IUGR) has been a major clinical and research
      issue since the disease was first reported. This review evaluates the current
      evidence for prediction and prevention of preeclampsia and IUGR using clinical
      tests, maternal serum markers, and uterine artery Doppler screening. In addition,
      we critically evaluate the evidence regarding the different therapeutic
      strategies for the prevention of preeclampsia and IUGR and the latest clinical
      recommendations for their use.

PMID- 16289645
TI  - Non-compliance with the re-excision guidelines for cutaneous melanoma in The
      Netherlands does not influence survival.
AB  - AIM: To evaluate causes and consequences of not adhering to the clinical practice
      guideline for cutaneous malignant melanoma. METHODS: We conducted a retrospective
      cohort study of the clinical records of 454 subjects whose pathological reports
      were obtained from a population-based cancer registry to assess determinants and
      effects of non-compliance of physicians with the excision policy and the related
      clinical practice guideline for patients with primary localized cutaneous
      malignant melanoma (CMM). A comparative analysis was performed of patients who
      did and did not undergo re-excision (compliance versus non-compliance with the
      guideline). Subjects diagnosed in 1988, 1993 and 1997, just 1 year after
      publication of the (adapted) guideline, were followed until death due to any
      cause or until July 1st 2003. RESULTS: Old age was the most important determinant
      of non-compliance. After adjusting for age at diagnosis, gender, subsite and
      Breslow thickness there was no significant difference in overall survival between
      the compliance group and the non-compliance group. CONCLUSIONS: Non-compliance to
      the guideline is more common in older patients and in patients with melanoma in
      the head and neck region. After adjusting for confounders, a significant effect
      of complying with the guidelines on overall survival could not be observed.

PMID- 16289646
TI  - Association of genetic polymorphisms of MK, IL-4, p16, p21, p53 genes and human
      gastric cancer in Taiwan.
AB  - AIMS: To assess gastric cancer risk and clinical-pathological factors associated
      with genetic polymorphisms of MK, IL-4, p16, p21 and p53 genes. METHODS: A
      retrospective study was conducted for 123 patients who had recently developed
      primary gastric cancer. Clinical data and pathological findings were collected,
      genetic polymorphisms of MK, IL-4, p16, p21 and p53 genes were analysed, and the
      associations of genetic polymorphisms with gastric cancer carcinogenesis were
      evaluated. RESULTS: There was significant association of genetic polymorphisms
      between gastric cancer and control groups in p53 genes. After further
      stratification of the cancer group into different clinical-pathologic parameters,
      there were significant associations in the sex and LN involvement groups in MK
      gene; alcohol consumption group in p16 gene; age and cell differentiation groups
      in p21 gene; age and tumour location groups in p53 gene; but we fail to find any
      significant association with IL-4 gene polymorphisms. CONCLUSIONS: Genetic
      susceptibility testing is a tool to evaluate the association of genetic
      polymorphisms with gastric cancer carcinogenesis.

PMID- 16289647
TI  - Sentinel lymph node in carcinoma of the anal canal: a review.
AB  - AIMS: To review the studies investigating the efficacy of the sentinel lymph node
      (SLN) procedure in anal canal carcinoma and to evaluate its potential role in
      guiding a more selective approach for patients with the malignancy. METHODS: A
      literature search in the PubMed database was preformed using the key words
      "sentinel lymph node" and "anal cancer". All indexed original articles (except
      case reports) on the SLN procedure in cancer of the anal canal were analysed.
      RESULTS: There are five published series to date. Eighty-four patients were
      studied. Rates of SLN detection and removal ranged from 66 to 100% of patients
      investigated. Nodal metastases were found in 7.1 to 42% of cases. No serious
      complications were reported. CONCLUSIONS: The technique has proven to be safe and
      effective in sampling inguinal SLNs. The detection of occult metastases in
      clinically unsuspicious nodes represents an important improvement in the process
      of staging these patients, which has not been possible with any other method of
      diagnosis. Although SLN procedure is still in an early phase of investigation in
      this type of cancer, it emerges as an objective method to guide individual
      therapeutic decisions.

PMID- 16289648
TI  - Appropriate technology for rural India - solar decontamination of water for
      emergency settings and small communities.
AB  - A commercial solar water heating system was evaluated for its effectiveness in
      decontaminating drinking water with a view to use in emergency situations. A
      total of 18 seeding experiments carried out over 6 months with 10(5) to
      10(7)Escherichia coli/ml showed that the solar heater produced 125 l of
      bacteriologically safe water in 4 h when the ambient temperature was above 30
      degrees C, with a holding time of at least 2 h. The solar water heating system is
      inexpensive, easy to transport and set up and could provide safer drinking water
      for 50 people a day. It would be effective in the decrease and prevention of
      waterborne disease in emergency situations, and is appropriate for use in small
      communities.

PMID- 16289649
TI  - Underestimation of snakebite mortality by hospital statistics in the Monaragala
      District of Sri Lanka.
AB  - Estimates of snakebite mortality are mostly based on hospital data, although
      these may considerably underestimate the problem. In order to determine the
      accuracy of hospital-based statistics, data on snakebite mortality in all
      hospitals in the Monaragala District of Sri Lanka were compared to data on
      snakebite as the certified cause of death for the district, for the 5-year period
      between 1999 and 2003. Data were cross-checked in a sample of hospitals and
      divisional secretariats within the district. Hospital statistics did not report
      45 (62.5%) of the true number of snakebite deaths in the Monaragala District.
      Twenty-six (36.1%) of the victims either did not seek, or had no access to, a
      hospital. Another 19 (26.4%) had arrived at hospital, but had done so too late to
      receive treatment. Our study confirms the limitations of official hospital-based
      mortality data on snakebite.

PMID- 16289650
TI  - A high prevalence of HIV-1 infection among pregnant women living in a rural
      district of north Uganda severely affected by civil strife.
AB  - This study aims at estimating the recent trends in HIV-1 prevalence and the
      factors associated with infection among pregnant women in the Gulu District of
      north Uganda, a rural area severely affected by civil strife. In 2000-2003, a
      total of 4459 antenatal clinic attendees of Lacor Hospital were anonymously
      tested for HIV-1 infection. The overall and age-specific prevalence did not show
      any significant trend over time. The age-standardized prevalence slightly
      declined, from 12.1% in 2000 to 11.3% in 2003. Increased age [20-24 years:
      adjusted odds ratio (AOR) 1.63; 95% CI 1.18-2.25; >or=25 years: AOR 2.56; 95% CI
      1.91-3.44], residence in urban areas (AOR 1.76; 95% CI 1.41-2.18), being
      unmarried (AOR 1.60; 95% CI 1.27-2.01), increased age of partner (25-34 years:
      AOR 1.87; 95% CI 1.29-2.73; >or=35 years: AOR 2.68; 95% CI 1.72-4.16), modern
      occupation of partner (AOR 1.98; 95% CI 1.53-2.58), and short time of residence
      at the current address (AOR 1.36; 95% CI 1.05-1.76) were associated with
      infection. The HIV-1 prevalence in this rural district is high and similar to
      that observed in urban antenatal clinics, probably reflecting the effect of the
      last 18 years of civil strife.

PMID- 16289652
TI  - Enteral feeding in the critically ill: are nursing practices contributing to
      hypocaloric feeding?
AB  - INTRODUCTION: Enteral feeding is the preferred method of nutritional support for
      the critically ill; however, a significant number of these patients are under
      fed. It is possible that common nursing practices associated with the delivery of
      enteral feeding may contribute to under-feeding although there is little data
      available describing nursing practice in this area. METHOD: A descriptive survey
      based design was used to explore the enteral feeding practices of 376 critical
      care nurses (response rate 50.5%). Participants completed a 57-item survey that
      focused on general enteral feeding practice and the management of feeding
      intolerance and complications. RESULTS: The enteral feeding practice of critical
      care nurses varied widely and included some practices that could contribute to
      under-feeding in the critically ill. Practices associated with the measurement of
      gastric residual volumes (GRV) were identified as the most significant potential
      contributor to under-feeding. GRV measurements were commonly used to assess
      feeding tolerance (n = 338; 89.9%) and identified as a reason to delay feeding (n
      = 246; 65.4%). Delayed gastric emptying was frequently managed by prokinetic
      agents (n = 237; 63%) and decreasing the rate of feeding (n = 247; 65.7%) while
      nursing measures, such as changing patient position (n = 81; 21.5%) or checking
      tube placement (n = 94; 25%) were less frequently reported. CONCLUSION: The
      findings of this survey support the contention that nursing practices associated
      with the delivery of enteral feeds may contribute to under-feeding in the
      critically ill patient population.

PMID- 16289651
TI  - A randomized trial comparing the efficacy of four treatment regimens for
      uncomplicated falciparum malaria in Assam state, India.
AB  - A four-arm drug sensitivity study compared chloroquine, sulfadoxine-pyrimethamine
      (SP), mefloquine and mefloquine-artesunate in Sonitpur and Karbi Anglong
      districts in Assam state, India. Two criteria were used to ascertain outcome:
      success of clinical treatment and parasitologic cure. In Sonitpur, at 14 days,
      there were 36/56 early and late treatment failures plus late parasitologic
      failures to chloroquine and 16/56 for SP. In Karbi Anglong, combined treatment
      failure at 14 days was 16/56 to chloroquine and 8/60 to SP. Mefloquine and
      mefloquine-artesunate demonstrated 93.9% and 93.6% sustained responses
      respectively at 42 days. High failure rates to both chloroquine and SP preclude
      the use of these drugs as first-line treatment for uncomplicated falciparum
      malaria in this region. A mefloquine-artesunate combination presents an effective
      alternative utilizing the currently recommended higher dose of mefloquine.

PMID- 16289653
TI  - Comparison of exposure assessment methods in occupational exposure to benzene in
      gasoline filling-station attendants.
AB  - The aim of this study was to assess gasoline filling-station attendants' exposure
      to benzene and to determine which biological exposure index (BEI), trans,trans
      muconic acid (t,t-MA) or S-phenylmercapturic acid (S-PMA), shows better
      correlation with environmental exposure. Exposure to benzene was measured using
      passive samplers (Radiello) attached to the collar of the overalls of subjects
      (n=33) just before the work-shift (approximately 8h); analysis was performed by
      GC-FID. S-PMA and t,t-MA were determined, respectively, by an
      immunochemiluminescent assay based on specific monoclonal antibodies and by HPLC
      UV at 264 nm. Both methods of biological monitoring were performed on beginning
      and end-shift urine samples, and expected t,t-MA and S-PMA values were
      calculated. Smoking habits and life-style were ascertained by means of a
      questionnaire. Both environmental and biological monitoring data showed that
      benzene exposure for gasoline filling-station attendants was low when compared
      with the respective ACGIH limit values (means-benzene: 0.044 mg/m(3); t,t-MA: 171
      microg/g creatinine; S-PMA: 2.7 microg/g creatinine). No significant correlation
      was found between exposure to benzene and t,t-MA or S-PMA excretion data. The use
      of expected values was also experimented for S-PMA and t,t-MA. This consists of
      calculating, on the basis of the known half-life of the benzene metabolite, the
      concentration of that metabolite that a worker should present at the end of the
      work-shift, the difference between this value and the value actually found is a
      measure of benzene exposure during work. The use of expected values in biological
      monitoring did not improve correlations. At these low benzene levels,
      environmental monitoring seems to be the best method of evaluating individual
      exposure. However, biological monitoring remains useful, as a mean of assessing
      group exposure.

PMID- 16289654
TI  - Evaluation of exposure to 1-alkoxy-2-propanols and 1-(2-methoxy-1-methylethoxy)-2
      propanol by the analysis of the parent compounds in urine.
AB  - Floor lacquerers' inhalation and total exposure to 1-alkoxy-2-propanols and 1-(2
      methoxy-1-methylethoxy)-2-propanol (DPGME) were measured. The total exposure was
      biomonitored by urinalysis of free unchanged 1-alkoxy-2-propanols and DPGME. The
      floor lacquerers' 8-h inhalation exposures to 1-methoxy-2-propanol (PGME), 1
      butoxy-2-propanol (PGBE) and DPGME were 1.9+/-1.3 (mean+/-S.D., n=15), 1.0+/
      1.4ppm (n=11) and 0.2+/-0.3ppm (n=11), respectively. The gravity-corrected
      urinary excretions of PGME, PGBE and DPGME were 5.3+/-5.4mumol/l, 0.9+/
      0.9mumol/l and 1.5+/-2.8mumol/l, respectively. A linear relationship was found
      between the gravity-corrected urinary excretion of PGME (R(2)=0.82), PGBE
      (R(2)=0.93) and DPGME (R(2)=0.93) and their preceding 8-h inhalation exposure.
      The correlations between the uncorrected urinary excretions and inhalation
      exposures to PGME, PGBE and DPGME was also calculated and found good (R(2)=0.82
      0.95). The effect of work strain on the total exposure seemed to be more relevant
      in the exposure to hydrophilic PGME than in the exposure to more lipophilic PGBE.

PMID- 16289655
TI  - Translational enhancement of HCV RNA genotype 1b by 3'-untranslated and envelope
      2 protein-coding sequences.
AB  - HCV RNA has a unique regulatory mechanism for translation. The X region of 3'-UTR
      and core-coding sequence regulate HCV translation. In this study, we clarified
      that the entire 3'-UTR also enhances HCV translation, and the envelope-coding
      sequence of HCV genotype 1b increases degree of this enhancement. In the
      luciferase reporter assay using rabbit reticulocyte lysates, translational
      enhancement by 3'-UTR with core to E2 regions was 25-fold higher when compared
      with control RNA lacking the 3'-UTR. Presence of the entire E2 sequence was
      important for this enhancement. This phenomenon was not due to transcript
      stability, and envelope protein alone did not affect translation. E2-coding
      sequence of genotype 1a had no effect on translation. We observed the same
      results in animal cell culture systems using bicistronic RNA. Structural protein
      coding sequences and 3'-UTR of HCV RNA regulate viral translation, and a target
      for antiviral agents may be present in these regions.

PMID- 16289656
TI  - Inhibition of HIV-1 virus replication using small soluble Tat peptides.
AB  - Although the introduction of highly active antiretroviral therapy (HAART) has led
      to a significant reduction in AIDS-related morbidity and mortality,
      unfortunately, many patients discontinue their initial HAART regimen, resulting
      in development of viral resistance. During HIV infection, the viral activator Tat
      is needed for viral progeny formation, and the basic and core domains of Tat are
      the most conserved parts of the protein. Here, we show that a Tat 41/44 peptide
      from the core domain can inhibit HIV-1 gene expression and replication. The
      peptides are not toxic to cells and target the Cdk2/Cyclin E complex, inhibiting
      the phosphorylation of serine 5 of RNAPII. Using the Cdk2 X-ray crystallography
      structure, we found that the low-energy wild-type peptides could bind to the ATP
      binding pocket, whereas the mutant peptide bound to the Cdk2 interface. Finally,
      we show that these peptides do not allow loading of the catalytic domain of the
      cdk/cyclin complex onto the HIV-1 promoter in vivo.

PMID- 16289657
TI  - The gammac-cytokine regulated transcription factor, STAT5, increases HIV-1
      production in primary CD4 T cells.
AB  - Although HIV-1 (HIV) replicates poorly in non-dividing CD4 lymphocytes, resting T
      cells contribute to the latent reservoir. The gammac-related cytokines reverse
      this block to HIV infection; however, the molecular mechanisms controlling this
      process are not understood. We asked whether the gammac-cytokine regulated
      transcription factor, signal transducer and activator of transcription 5 (STAT5),
      activates HIV transcription. We identified three regions in the long terminal
      repeat (LTR) as close matches to the STAT5 consensus-binding site and show that
      STAT5 binds the LTR during HIV infection. Expression of Janus kinase 3 (JAK3) or
      STAT5 in primary human CD4 T cells activated LTR transcription, while
      transactivation-incompetent dominant-negative STAT5 inhibited JAK3-induced LTR
      activity and infection of activated HIV-producing CD4 T-cells. In addition,
      overexpression of STAT5 increased virus production in unstimulated primary T
      cells - both the number of p24+ cells and their level of p24 production -
      suggesting that STAT5 promotes a permissive state for HIV infection. These data
      may have implications for regulation of latency and therapeutic strategies for
      control of HIV disease.

PMID- 16289659
TI  - Effect of N-acetyl-L-cysteine on ROS production and cell death caused by HEMA in
      human primary gingival fibroblasts.
AB  - Previous investigations have shown that 2-hydroxyethyl methacrylate (HEMA) causes
      reactive oxygen species (ROS) production, which in turn affects cell survival and
      cell death. The purpose of this study was to evaluate the effects of the
      antioxidant N-acetyl-L-cysteine (NAC) on HEMA-induced toxicity in human primary
      gingival fibroblasts (HGF). HGF were treated with various concentrations of HEMA
      (0-12 mm) in the absence and presence of NAC (1, 5, and 10 mm). The 3-(4,5
      dimethyiazol-2-1)-2-5-diphenyl tetrazolium bromide (MTT) assay was used to
      evaluate the mitochondrial dehydrogenase activity after HEMA exposure. Viability
      and cell death were determined by flow cytometry using Annexin V and PI staining.
      ROS production was detected by the increasing fluorescence of the oxidation
      sensitive dye 2',7'-dichlorofluorescein diacetate (DCFH-DA) after HEMA treatment.
      After a 24h incubation period, HEMA concentrations higher then 10mm caused a
      decrease of cell viability, mitochondrial activity, and an increase of cell
      death. HEMA concentrations of 4-12 mm markedly increased ROS levels in a dose
      dependent manner. High NAC concentrations (5 and 10 mm) significantly reduced
      cell death, and restored the mitochondrial activity after a 24 h co-treatment,
      but 1 mm NAC increased HEMA toxicity (p<0.05). All NAC concentrations
      significantly reduced ROS levels induced by HEMA after a 2 h exposure (p<0.05),
      but no such reduction was observed after a 4 h treatment. Furthermore, treatment
      with 10 mm HEMA and 1 mm NAC for 6h caused an increase in ROS levels compared to
      10 mm HEMA alone (p<0.05). In conclusion, our results suggest that high NAC
      concentrations protect HGF against HEMA cytotoxicity by reducing the induced ROS
      levels.

PMID- 16289658
TI  - Leukemia virus long terminal repeat activates NFkappaB pathway by a TLR3
      dependent mechanism.
AB  - The long terminal repeat (LTR) region of leukemia viruses plays a critical role
      in tissue tropism and pathogenic potential of the viruses. We have previously
      reported that U3-LTR from Moloney murine and feline leukemia viruses (Mo-MuLV and
      FeLV) upregulates specific cellular genes in trans in an integration-independent
      way. The U3-LTR region necessary for this action does not encode a protein but
      instead makes a specific RNA transcript. Because several cellular genes
      transactivated by the U3-LTR can also be activated by NFkappaB, and because the
      antiapoptotic and growth promoting activities of NFkappaB have been implicated in
      leukemogenesis, we investigated whether FeLV U3-LTR can activate NFkappaB
      signaling. Here, we demonstrate that FeLV U3-LTR indeed upregulates the NFkappaB
      signaling pathway via activation of Ras-Raf-IkappaB kinase (IKK) and degradation
      of IkappaB. LTR-mediated transcriptional activation of genes did not require new
      protein synthesis suggesting an active role of the LTR transcript in the process.
      Using Toll-like receptor (TLR) deficient HEK293 cells and PKR(-/-) mouse embryo
      fibroblasts, we further demonstrate that although dsRNA-activated protein kinase
      R (PKR) is not necessary, TLR3 is required for the activation of NFkappaB by the
      LTR. Our study thus demonstrates involvement of a TLR3-dependent but PKR
      independent dsRNA-mediated signaling pathway for NFkappaB activation and thus
      provides a new mechanistic explanation of LTR-mediated cellular gene
      transactivation.

PMID- 16289660
TI  - Effects of single non-ortho, mono-ortho, and di-ortho chlorinated biphenyls on
      human sperm functions in vitro.
AB  - Polychlorinated biphenyls (PCBs) are ubiquitous pollutants in the environment.
      They are present in body fluids associated with reproduction such as follicular
      fluid, seminal fluid and cervical mucus. Most PCB effects are mediated through
      the aryl hydrocarbon receptor, which is present in human spermatozoa.
      Additionally, PCBs may alter various biochemical reactions, such as calcium
      homeostasis. Therefore we investigated the effects of single non-ortho PCB 126,
      mono-ortho PCB 118, and di-ortho PCB 153 on human sperm motility, vitality, and
      calcium-dependent acrosome reaction (AR) in vitro. Human spermatozoa were either
      treated with different single PCB congeners or their combinations for 5 h at 37
      degrees C (spontaneous AR), or for 16 h at room temperature and 4 degrees C
      (induced AR). Motility was measured after 5 h of incubation. Compared with the
      controls, PCB exposure had no effects on the percentage of living acrosome
      reacted spermatozoa, vitality, and motility. There was no difference in the
      inducibility of the AR between treatment groups and the respective controls after
      long term incubation. The PCB concentrations used were far higher than those
      found in cervical mucus or seminal fluid. In vivo effects of PCB congeners on
      human ejaculated spermatozoa seem to be unlikely. However these results cannot be
      easily transferred to the in vivo situation, because individual susceptibility
      has to be considered, and there is no information about synergistic or additive
      effects with other chemicals present in the male and female reproductive tract.

PMID- 16289661
TI  - Synthesis and comparative molecular field analysis (CoMFA) of argentatin B
      derivatives as growth inhibitors of human cancer cell lines.
AB  - Synthesis, characterization, anticancer activity, and comparative molecular field
      analysis (CoMFA) of 14 argentatin B (1) analogs are described. The effect of
      argentatin B derivatives on the growth of K562 (leukemia), PC-3 (prostate), U251
      (CNS), and HCT-15 (colon) human cancer cell lines was determined using the
      sulforhodamine B test. The most active compound in this series, 2-formyl
      (16beta,24R)-16,24-epoxy-25-hydroxycycloart-1-en-3-one (12), was about 35-50
      times more potent than argentatin B (1). Structures were built using the X-ray
      crystallography of six derivatives for 3D modeling with Sybyl6.9. CoMFA of Log
      (1/IC50) in K562 cell line gave q2 = 0.507, r2 = 0.907, and three components. The
      standard deviation CoMFA contours indicate that increased activity is associated
      with a bulky group at C-2, a C1-C2 double bond, and low electronic density at C
      25. Experimental Log P values for argentatin B and one derivative were 1-2 Log
      units more hydrophilic than the calculated CLog P values.

PMID- 16289663
TI  - Ultra-rapid object detection with saccadic eye movements: visual processing speed
      revisited.
AB  - Previous ultra-rapid go/no-go categorization studies with manual responses have
      demonstrated the remarkable speed and efficiency with which humans process
      natural scenes. Using a forced-choice saccade task we show here that when two
      scenes are simultaneously flashed in the left and right hemifields, human
      participants can reliably make saccades to the side containing an animal in as
      little as 120 ms. Low level differences between target and distractor images were
      unable to account for these exceptionally fast responses. The results suggest a
      very fast and unexpected route linking visual processing in the ventral stream
      with the programming of saccadic eye movements.

PMID- 16289662
TI  - Evaluation of the photostability of different UV filter combinations in a
      sunscreen.
AB  - Development of photostable sunscreens is extremely important to preserve the UV
      protective capacity and to prevent the reactive intermediates of photounstable
      filter substances behaving as photo-oxidants when coming into direct contact with
      the skin. Thus, the objective of this study was to evaluate the photostability of
      four different UV filter combinations in a sunscreen by using HPLC analysis and
      spectrophotometry. The formulations that were investigated included four
      different UV filter combinations often used in SPF 15 sunscreens. The UV filter
      combinations were: octyl methoxycinnamate (OMC), benzophenone-3 (BP-3) and octyl
      salicylate (OS) (formulation 1); OMC, avobenzone (AVB) and 4-methylbenzilidene
      camphor (MBC) (formulation 2); OMC, BP-3 and octocrylene (OC) (formulation 3);
      OMC, AVB and OC (formulation 4). In the photostability studies, 40 mg of each
      formulation were spread onto a glass plate and left to dry before exposure to
      different UVA/UVB irradiation. Exposed samples were then immersed in isopropanol
      and the dried film dissolved ultrasonically. The filter components in the
      resulting solution were quantified by HPLC analysis with detection at 325 nm and
      by spectrophotometry. In this study, the four UV filter combinations showed
      different photostability profiles and the best one was formulation 3 (OMC, BP-3
      and OC), followed by formulations 4, 1 and 2. In addition, OC improved the
      photostability of OMC, AVB and BP-3.

PMID- 16289664
TI  - Voltage-dependent ion channels in the mouse RPE: comparison with Norrie disease
      mice.
AB  - We studied electrophysiological properties of cultured retinal pigment epithelial
      (RPE) cells from mouse and a mouse model for Norrie disease. Wild-type RPE cells
      revealed the expression of ion channels known from other species: delayed
      rectifier K(+) channels composed of Kv1.3 subunits, inward rectifier K(+)
      channels, Ca(V)1.3 L-type Ca(2+) channels and outwardly rectifying Cl(-)
      channels. Expression pattern and the ion channel characteristics current density,
      blocker sensitivity, kinetics and voltage-dependence were compared in cells from
      wild-type and Norrie mice. Although no significant differences were observed, our
      study provides a base for future studies on ion channel function and dysfunction
      in transgenic mouse models.

PMID- 16289665
TI  - Large shifts in perceived motion direction reveal multiple global motion
      solutions.
AB  - Moving objects are thought to be decomposed into one-dimensional motion
      components by early cortical visual processing. Two rules describing how these
      components might be re-combined to produce coherent object motion are the
      intersection of constraints and the vector average rules. Using stimuli for which
      these combination rules predict different directional solutions, we found that
      adapting one of the solutions through motion adaptation switched perceived
      direction to the other solution. The effects were symmetrical: shifts from IOC to
      VA, and from VA to IOC, were observed following adaptation. These large shifts
      indicate that multiple solutions to global motion processing coexist and compete
      to determine perceived motion direction.

PMID- 16289666
TI  - CR1 on erythrocytes of Brazilian systemic lupus erythematosus patients: the
      influence of disease activity on expression and ability of this receptor to bind
      immune complexes opsonized with complement from normal human serum.
AB  - Hypocomplementaemia and low expression of CR1 on erythrocytes (E) of patients
      with systemic lupus erythematosus (SLE) are associated with defective clearance
      of circulating immune complexes (IC) and so they may have pathogenic
      significance. Here, we investigated whether the reduced CR1/E in SLE patients per
      se might affect the binding of IC to CR1/E. First, we analysed the expression of
      CR1 on E of active (n=30) and inactive (n=34) SLE patients using a FITC
      conjugated mouse anti-CR1 monoclonal antibody E11 and flow cytometry. Both groups
      of patients had a significantly reduced CR1/E expression compared with healthy
      controls (n=40). It was also observed that the number of E bearing CR1 was
      reduced in both groups of SLE patients studied. Second, we determined the
      functional activity of CR1/E by measuring the binding to E of FITC-bovine serum
      albumin (BSA)/rabbit anti-BSA complexes, formed at equivalence, which were
      opsonized with complement from normal human serum (NHS). On the other hand, we
      did not find differences between the patient and control groups in the ability of
      E to bind IC/NHS. There was also a positive correlation between the CR1/E
      expression and the number of E bearing CR1 in control and inactive SLE groups,
      which was not observed in the group of active SLE patients. Considering the
      involvement of low levels of complement and CR1/E expression on complex
      processing, in this in vitro model the results show that an effective coating of
      the complexes with complement is sufficient to bind them preferentially to CR1
      over normal levels of receptor expression.

PMID- 16289667
TI  - Expression and localization of alpha-fetoprotein mRNA and protein in human early
      villous trophoblasts.
AB  - Alpha-fetoprotein (AFP) is a major plasma protein produced during human fetal
      life. It is a good marker for several possible disorders affecting gestation. We
      previously reported that afp gene expression, which takes place mainly in yolk
      sac and fetal liver, also occurs in normal human placenta, specifically in early
      pregnancy. The aim of the present study was to determine the precise location of
      AFP synthesis sites within the placental villi. In situ hybridization and
      immunohistochemical experiments were performed on sections obtained from
      placentas of first-trimester and full-term pregnancies. We found that the pattern
      of afp gene expression was restricted to specific villous trophoblastic areas in
      early placentas. Both afp transcripts and AFP protein were mainly located in
      discontinuous regions, at junctions between two villi and at budding sites. In
      contrast, no AFP expression was detected in the cytotrophoblastic extravillous
      proliferative zone or in other placental cell types. According to the earlier
      studies, no AFP synthesis was detected in placental villous tissue from full-term
      pregnancies, using in situ hybridization and immunohistochemistry.

PMID- 16289668
TI  - Innovative procedure for the determination of gross-alpha/gross-beta activities
      in drinking water.
AB  - An alternative sample preparation method for the determination of gross
      alpha/beta activity concentrations in drinking water is introduced in this paper.
      After the freeze-drying of tap water samples, determination by liquid
      scintillation counting can be applied utilizing alpha/beta separation. It has
      been shown that there is no adsorption or loss of solid radionuclides during the
      freeze-drying procedure. However, the samples have to be measured quickly after
      the preparation since the ingrowth of daughter isotopes negatively effects the
      measurement. The limits of detection for gross-alpha and gross-beta activity are
      in the range 25-210 mBq/l, respectively, for a measurement time of only 8-9 h.

PMID- 16289669
TI  - Evaluation of two computational models of amplitude modulation coding in the
      inferior colliculus.
AB  - Two computational models replicating amplitude-modulation encoding in the
      inferior colliculus (IC) are presented and compared. Neurons in this nucleus are
      modeled as point neurons using Mc Gregor equations, and receive depolarizing
      currents from action potentials delivered by stellate cells (chopper units) in
      the cochlear nucleus (CN). Stellate cells are modeled using modified Hodgkin
      Huxley equations and receive inputs from a peripheral auditory model. The CN
      models of the two proposed architectures are characterized by an important
      dispersion of cellular characteristics, and therefore by various cellular best
      modulation frequencies (BMFs) ranging from 60 to 300 Hz. In contrast with the
      previous model proposed by [M.J. Hewitt, R. Meddis, A computer model of amplitude
      modulation sensitivity of single units in the inferior colliculus, J. Acoust.
      Soc. Am. 95 (1994) 2145], each IC cell model receives convergent input from
      stellate cells with various BMFs. This approach assumes therefore minimal
      constraints on the model architecture and cell characteristics. The two models
      differ in terms of the neuronal structure of the IC, composed of 1 or 2 layers of
      point neurons acting as coincidence detectors. Each model is evaluated using two
      metrics: mean firing rate and modulation gain. Rate and temporal modulation
      transfer functions (r-MTFs and t-MTFs, respectively) are simulated and compared
      with physiological data. Simulations reveal that (i) an important dispersion of
      BMFs in the CN cells providing input to IC cells yields plausible IC cells
      responses to AM stimuli, (ii) the 2-layer IC structure yields the best
      approximation of IC responses measured in vivo.

PMID- 16289670
TI  - Using a battery of bioassays, benthic phytoplankton and the AUSRIVAS method to
      monitor long-term coal tar contaminated sediment in the Cache la Poudre River,
      Colorado.
AB  - This survey provides information on sediment toxicity and structural
      characteristics of the macroinvertebrates and benthic phytoplankton at 10
      locations in the Cache la Poudre River after long-term exposure to coal tar
      residue. The application of the Australian river bioassessment system (AUSRIVAS)
      as well as a biotest battery was used to evaluate the river 'health' condition.
      Coal tar is a dense nonaqueous-phase liquid of significant environmental concern
      due to its toxicity and persistence in the subsurface. Organisms like Selenastrum
      capricornutum, Daphnia magna and Chironomus tentans, representing different
      complexities in the biosphere, were selected as test systems for ecotoxicological
      studies. The results obtained in this study indicate that a biotest battery,
      macroinvertebrate and benthic phytoplankton communities are in principle suitable
      biological tools for evaluation of toxic oil and coal-derived substances in long
      term contaminated river sediment.

PMID- 16289671
TI  - Evaluation of kinetic parameters of a sulfur-limestone autotrophic
      denitrification biofilm process.
AB  - In this study, four kinetic parameters of autotrophic denitrifiers in fixed-bed
      sulfur-limestone autotrophic denitrification (SLAD) columns were evaluated. The
      curve-matching method was used by conducting 22 non-steady-state tests for
      estimation of half-velocity constant, K(s) and maximum specific substrate
      utilization rate, k. To estimate the bacteria yield coefficient, Y and the decay
      coefficient, k(d), two short term batch tests (before and after the starvation of
      the autotrophic denitrifiers) were conducted using a fixed-bed SLAD column where
      the biofilm was fully penetrated by nitrate-N. It was found that K(s) = 0.398 mg
      NO(3-)-N/l, k = 0.15 d(-1), k(d) = 0.09-0.12 d(-1), and Y = 0.85-1.11 g VSS/g
      NO(3-)-N. Our results are consistent with those obtained from SLAD biofilm
      processes, but different from those obtained from suspended-growth systems with
      thiosulfate or sulfur powders as the S source. The method developed in this study
      might be useful for estimation of four Monod-type kinetic parameters in other
      biofilm processes. However, cautions must be given when the estimated parameters
      are used because the measurements of the biomass and the biofilm thickness could
      be further improved, and the assumption of sulfur being a non-limiting substrate
      needs to be proved.

PMID- 16289672
TI  - Seasonal occurrence and degradation of 2-methylisoborneol in water supply
      reservoirs.
AB  - Methylisoborneol (MIB) and geosmin are cyanobacterial metabolites that occur at
      nanograms per liter levels in surface water supplies and are responsible for many
      taste and odor complaints about the aesthetics of drinking water. This study
      evaluated three water supply reservoirs with bottom-release (hypolimnion) outlet
      structures in Arizona. MIB concentrations were always higher than geosmin
      concentrations, but both followed similar seasonal trends. MIB concentrations
      increased from spring to late summer, and stratified vertically with depth in the
      water column; the highest concentrations were always in the upper 10 m of the
      water column. Thermal destratification in the autumn increased MIB concentrations
      released from the outlet of reservoirs and impacted downstream utilities for
      several months. By winter of each year MIB concentrations were non-detectable.
      Mass balance analyses on MIB indicated that in-reservoir reactions were more
      important in changing MIB concentrations than conservative hydraulic "flushing"
      of the reservoir. Maximum net loss rates for MIB in the field (R(F,max)) were on
      the order of 0.23-1.7 ng/L-day, and biodegradation appeared more important than
      volatilization, photolysis or adsorption. Using lake water in laboratory
      experiments, bacterial biodegradation rates (R(L)) ranged from 0.5-1 ng/L-day and
      were comparable to R(F,max) values. Based upon these rates, MIB concentrations in
      a reservoir would decrease by approximately 30 ng/L over a period of 1 month.
      This was the magnitude change in MIB concentrations commonly observed after
      autumn thermal destratification of the reservoirs.

PMID- 16289673
TI  - Hydrogen and electricity production from a food processing wastewater using
      fermentation and microbial fuel cell technologies.
AB  - Hydrogen can be produced from fermentation of sugars in wastewaters, but much of
      the organic matter remains in solution. We demonstrate here that hydrogen
      production from a food processing wastewater high in sugar can be linked to
      electricity generation using a microbial fuel cell (MFC) to achieve more
      effective wastewater treatment. Grab samples were taken from: plant effluent at
      two different times during the day (Effluents 1 and 2; 735+/-15 and 3250+/-90 mg
      COD/L), an equalization tank (Lagoon; 1670+/-50mg-COD/L), and waste stream
      containing a high concentration of organic matter (Cereal; 8920+/-150 mg-COD/L).
      Hydrogen production from the Lagoon and effluent samples was low, with 64+/-16 mL
      of hydrogen per liter of wastewater (mL/L) for Effluent 1, 21+/-18 mL/L for
      Effluent 2, and 16+/-2 mL/L for the Lagoon sample. There was substantially
      greater hydrogen production using the Cereal wastewater (210+/-56 mL/L). Assuming
      a theoretical maximum yield of 4 mol of hydrogen per mol of glucose, hydrogen
      yields were 0.61-0.79 mol/mol for the Cereal wastewater, and ranged from 1 to
      2.52 mol/mol for the other samples. This suggests a strategy for hydrogen
      recovery from wastewater based on targeting high-COD and high-sugar wastewaters,
      recognizing that sugar content alone is an insufficient predictor of hydrogen
      yields. Preliminary tests with the Cereal wastewater (diluted to 595 mg-COD/L) in
      a two-chambered MFC demonstrated a maximum of 81+/-7 mW/m(2) (normalized to the
      anode surface area), or 25+/-2 mA per liter of wastewater, and a final COD of <30
      mg/L (95% removal). Using a one-chambered MFC and pre-fermented wastewater, the
      maximum power density was 371+/-10 mW/m(2) (53.5+/-1.4 mA per liter of
      wastewater). These results suggest that it is feasible to link biological
      hydrogen production and electricity producing using MFCs in order to achieve both
      wastewater treatment and bioenergy production.

PMID- 16289674
TI  - Electrochemical degradation of 1,2- dichloroethane (DCA) in a synthetic
      groundwater medium using stainless-steel electrodes.
AB  - The electrochemical degradation of 1,2-dichloroethane (DCA) was examined in a
      synthetic groundwater medium. An undivided electrolytic reactor constructed with
      304 L-type stainless-steel plate electrodes was employed in all experiments. The
      removal of total organic carbon (TOC) content during the electrolysis of DCA was
      experimentally examined. Stainless-steel plate electrodes were effective in
      degrading DCA under experimental conditions including varying initial
      concentrations, chloride concentrations, electrolyte conductivities and applied
      current densities. A half-life method demonstrated TOC removal followed zero
      order kinetics under the experimental conditions examined. Chlorides
      concentration and applied current affected the TOC removal rates. An increase in
      current density increased the rate of TOC removal but caused a reduction in
      mineralization current efficiency. Increase in electrolyte conductivity had no
      effect on TOC removal rates but it decreased the energy consumption by reducing
      the cell voltage. Reaction temperature was shown to affect the TOC removal and
      was modeled by the Arrhenius equation.

PMID- 16289675
TI  - Melatonin reduces the severity of anesthesia-induced apoptotic neurodegeneration
      in the developing rat brain.
AB  - General anesthetics cause widespread apoptotic neurodegeneration in many regions
      of the developing rat brain. The activation of mitochondria-dependent apoptotic
      pathway is important in the early stages of anesthesia-induced developmental
      neuroapoptosis. To investigate potential means of protecting against this type of
      damage, we studied melatonin, a sleep-promoting agent and antioxidant known to
      inhibit apoptotic-type neuronal damage by improving mitochondrial homeostasis and
      stabilizing the inner mitochondrial membrane. When 7-day-old rats (the peak of
      synaptogenesis) were exposed to a commonly used and highly pro-apoptotic
      anesthesia cocktail (midazolam, isoflurane, nitrous oxide) in combination with
      the escalating doses of melatonin (from 1 to 20 mg/kg, s.c.), the severity of
      anesthesia-induced damage was reduced in a dose-dependent manner in two most
      vulnerable brain regions--the cerebral cortex and anterior thalamus. Melatonin
      induced neuroprotection was mediated, at least in part, via the inhibition of
      mitochondria-dependent apoptotic pathway since melatonin caused an up-regulation
      of the anti-apoptotic protein, bcl-X(L), reduction in anesthesia-induced
      cytochrome c release into the cytoplasm and a decrease in anesthesia-induced
      activation of caspase-3, an important step in the activation of DNAses and the
      formation of the apoptotic bodies.

PMID- 16289676
TI  - Randomized, double-blind study on effectiveness of intra-alveolar chlorhexidine
      gel in reducing the incidence of alveolar osteitis in mandibular third molar
      surgery.
AB  - Chlorhexidine (CHX) mouthwash is a good prophylactic agent for postextraction
      alveolar osteitis (AO), a very common complication. Recently, a bio-adhesive gel
      to deliver the active substance, CHX, has been introduced. The intra-alveolar
      positioning of the bio-adhesive gel allows more direct and prolonged action of
      CHX, which could be useful in the prevention of AO following extraction of
      impacted third molars. Presented here is a double-blind, randomised and parallel
      group study evaluating the efficacy of the bio-adhesive 0.2% CHX gel (n=53)
      applied once within the alveolus during third molar surgery, compared to placebo
      gel only (n=50), in reducing the incidence of impacted third-molar postextraction
      AO. A 63.33% reduction in the occurrence of AO (P=0.019) was observed in the
      experimental group. In the control group, the occurrence of AO was 30% compared
      to 11% in the experimental group. Bio-adhesive 0.2% CHX gel, applied only once
      within the alveolus site at the time of surgery, may reduce the incidence of AO
      following removal of impacted third molars.

PMID- 16289677
TI  - Calcium mobilization by nicotinic acid adenine dinucleotide phosphate (NAADP) in
      rat astrocytes.
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP) has been shown to release
      intracellular Ca(2+) in several types of cells. We have used Ca(2+)-sensitive
      fluorescent dyes (Fura-2, Fluo-4) to measure intracellular Ca(2+) in astrocytes
      in culture and in situ. Bath-applied NAADP elicited a reversible and
      concentration-dependent Ca(2+) rise in up to 90% of astrocytes in culture
      (EC(50)=7 microM). The NAADP-evoked Ca(2+) rise was maintained in the absence of
      extracellular Ca(2+), but was suppressed after depleting the Ca(2+) stores of the
      ER with ATP (20 microM), with cyclopiazonic acid (10 microM) or with ionomycin (5
      microM). P(2) receptor antagonist pyridoxalphosphate-6-azophenyl-2'4'-disulfonic
      acid (PPADS, 100 microM), IP(3) receptor blocker 2-aminoethoxydiphenyl borate (2
      APB, 100 microM) and PLC inhibitor U73122 (10 microM) also reduced or suppressed
      the NAADP-evoked Ca(2+) rise. NAADP still evoked a Ca(2+) response after
      application of glycyl-l-phenylalanine-beta-naphthylamide (GPN, 200 microM), which
      permeabilizes lysosomes, or preincubation with H(+)-ATPase inhibitor bafilomycin
      A1 (4 microM) and of p-trifluoromethoxy carbonyl cyanide phenylhydrazone (FCCP, 2
      microM), that impairs mitochondrial Ca(2+) handling. In acute brain slices, NAADP
      (10 microM) evoked Ca(2+) transients in cerebellar Bergmann glial cells and in
      hippocampal astrocytes. Our results suggest that NAADP recruits Ca(2+) from
      inositol 1,4,5-trisphosphate-sensitive Ca(2+) stores in mammalian astrocytes, at
      least partly by activating metabotropic P(2)Y receptors.

PMID- 16289678
TI  - Population genetics of nine STR loci from Baoan population in NW China.
AB  - Allele frequencies for the nine short tandem repeat (STR) loci (D3S1358, FGA,
      TH01, D7S820, VWA, CSF1PO, D5S818, D13S317, TPOX) were determined in a sample of
      120 unrelated individuals of the Baoan ethnic group living in northwest China.
      The values of observed heterozygosity (H), discrimination power (DP), a priori
      chance of exclusion (CE) and polymorphism information content (PIC) were
      calculated. All loci were in accordance with Hardy-Weinberg equilibrium (P=0.05).
      The obtained frequency distributions were compared with other previously reported
      population data.

PMID- 16289679
TI  - Implantation of radio frequency identification device (RFID) microchip in
      disaster victim identification (DVI).
AB  - The tsunami catastrophe of December 2004 left more than 200,000 dead. Disaster
      victim identification (DVI) teams were presented with the unprecedented challenge
      of identifying thousands of mostly markedly putrefied and partially skeletised
      bodies. To this end, an adequate body tagging method is essential. Conventional
      body bag tagging in terms of writing on body bags and placing of tags inside body
      bags proved unsatisfactory and problem prone due to consequences of cold storage,
      formalin (formaldehyde) embalming and body numbers inside storage facilities. The
      placement of radio frequency identification device (RFID) microchips inside
      victim bodies provided a practical solution to problems of body tagging and
      attribution in the DVI setting encountered by the Austrian DVI team in Thailand
      in early 2005.

PMID- 16289680
TI  - Reinforcing the anastomotic cuff in aortic dissection.

PMID- 16289681
TI  - The use of pamidronate in a leukemic child with immobilization hypercalcemia.

PMID- 16289682
TI  - Gene expression profiles of two accelerations in a CML patient.

PMID- 16289683
TI  - Rapid kindling in preclinical anti-epileptic drug development: the effect of
      levetiracetam.
AB  - PURPOSE: This study assesses the use of the serial day Rapid Kindling with
      Recurrent Hippocampal Seizures (RKRHS) model in drug testing by investigating the
      anti-epileptic effect of levetiracetam (LEV), a novel anti-epileptic drug (AED)
      with a unique preclinical profile. METHODS: Male Wistar rats (n=16) were
      implanted with a stimulation/recording electrode unit in the right hippocampus
      and epidural recording electrodes. One week later, all rats received 12
      stimulations each day for several consecutive days according to the serial day
      RKRHS protocol, until they were fully kindled. Fully kindled rats were then
      randomly assigned to an active (n=8) and a control (n=6) group and injected once
      (intraperitoneal, i.p.) with levetiracetam (54 mg/kg) or saline (0.9% NaCl, 2
      ml/kg), respectively. One hour later, the rats received additional kindling
      stimulations, during which the effect of LEV was assessed. RESULTS: One hour
      following injection of LEV, mean seizure stage dropped to 1.67+/-1.03 compared to
      5+/-0 in controls (p<0.05). Mean ADD was also significantly shorter in the active
      group than in controls; 21.16+/-5.03 s versus 57.24+/-8.16s, respectively
      (p<0.05). A gradual, time-dependent decline was noted in the anti-epileptic
      effect of LEV but this effect stayed statistically significant at least up to 2.5
      h (p<0.05). CONCLUSION: LEV was demonstrated to have anti-epileptic properties in
      RKRHS that compared to those in traditional kindling and contrast with results
      from classical screening tests. RKRHS may represent a valuable and sensitive
      screening tool early in the drug screening process.

PMID- 16289684
TI  - DFT-GIAO study of aryltetralin lignan lactones: conformational analyses and
      chemical shifts calculations.
AB  - The conformational properties of polygamain and morelensin, two aryltetralin
      lignan lactones, have been investigated in both the gas-phase and chloroform
      solution using DFT calculations at the B3LYP/6-311G(d,p) level. Results indicate
      that the conformation of polygamain is very rigid. Thus, the conformational
      flexibility of its five-membered rings is considerably restricted as reflects the
      pseudorotational parameters of the corresponding envelope conformations. On the
      other hand, morelensin shows a notable conformational flexibility, which is
      mainly due to its two methoxy groups. Accordingly, 16 minimum energy
      conformations with relative energies smaller than 2.4 kcal/mol were detected.
      Furthermore, chemical shifts for 13C nuclei have been calculated using the GIAO
      method, results being compared with experimental data. A good agreement was found
      for both polygamain and morelensin.

PMID- 16289685
TI  - Functional significance of Glu-77 and Tyr-137 within the active site of
      isoaspartyl dipeptidase.
AB  - Isoaspartyl dipeptidase (IAD) is a binuclear metalloenzyme and a member of the
      amidohydrolase superfamily. This enzyme catalyzes the hydrolytic cleavage of beta
      aspartyl dipeptides. The pH-rate profiles for the hydrolysis of beta-Asp-Leu
      indicates that catalysis is dependent on the ionization of two groups; one that
      ionizes at a pH approximately 6 and the other approximately 9. The group that
      must be ionized for catalysis is directly dependent on the identity of the metal
      ion bound to the active site. This result is consistent with the ionization of
      the hydroxide that bridges the two divalent cations. In addition to the residues
      that interact directly with the divalent cations there are two other residues
      that are highly conserved and found within the active site: Glu-77 and Tyr-137.
      Mutation of Tyr-137 to phenylalanine reduced the rate of catalysis by three
      orders of magnitude. The three dimensional X-ray structure of the Y137F mutant
      did not show any significant conformation changes relative to the three
      dimensional structure of the wild-type enzyme. The positioning of the side-chain
      phenolic group of Tyr-137 in the active site of IAD is consistent with the
      stabilization of the tetrahedral adduct concomitant with nucleophilic attack by
      the hydroxide that bridges the two divalent cations. Mutation of Glu-77 resulted
      in the reduction of catalytic activity by five orders of magnitude. The three
      dimensional structure of the E77Q mutant did not show any significant
      conformational changes in the mutant relative to the three dimensional structure
      of the wild-type enzyme. The positioning of the side-chain carboxylate of Glu-77
      is consistent with the formation of an ion pair interaction with the free alpha
      amino group of the substrate.

PMID- 16289686
TI  - Differential diagnostic test technology: sensitivity and specificity, an OIE
      validation perspective.
AB  - Companion differential diagnostic technology is extremely useful when utilized
      with marker vaccines for disease control and eradication. Examples of this
      technology include enzyme-linked immunoassays and particle concentration
      fluorescence immunoassays. The predictive values of such assays are dependent
      upon adequate validation of their diagnostic sensitivities and specificities. The
      World Organization for Animal Health (OIE) has put forth official guidelines for
      performing complete validation of diagnostic tests. This article presents an
      overview of these important guidelines.

PMID- 16289687
TI  - Position of the acetabular cup -- accuracy of radiographic calculation compared
      to CT-based measurement.
AB  - OBJECTIVE: A variety of mathematical and trigonometric methods has been described
      for determining the position of the acetabular cups from conventional
      radiographs. However, these formulae are subject to unduly large inaccuracies.
      The aim of the study was to compare the reliability and the accuracy of
      radiological and CT-based determination of acetabular cup position. MATERIALS AND
      METHODS: The positions of acetabular cups of 31 patients were calculated in
      conventional plain radiographs of the hip using the method described by Widmer.
      Further, in all patients computed tomograms of the pelvis were performed and the
      cup position was measured with the aid of a CT-based computer-assisted navigation
      software. As reference values inclination and anteversion of the cups were
      calculated in 3D reconstructions of the pelvis with the aid of an image
      processing software. RESULTS: The radiological measurement as well as the CT
      based method showed good intra- and inter-observer reliability and no significant
      difference in the calculation of the inclination (p=0.409). However, CT-based
      determination of anteversion was significantly more exact than radiological
      measurement (p<0.001). The calculation of the cup anteversion from the X-rays
      showed serious deviations from the reference method and a substantial error range
      (X-ray: mean deviation +1.74 degrees, range -16.6 degrees to +29.8 degrees , S.D.
      +/-9.32 degrees; CT-based: mean deviation -0.74 degrees, range -6.6 degrees to
      +5.3 degrees, S.D. +/-2.87). CONCLUSION: For any clinical problem or for clinical
      studies in which acetabular positions of acetabular cups have to be exactly
      determined, CT-based measuring methods are obviously the method of choice.
      Evaluations based only on conventional plain X-rays and calculation of the
      acetabular cup position using the formula described by Widmer must be regarded as
      unreliable, particularly, because of problems in measuring the anteversion.

PMID- 16289689
TI  - "A burden in your heart": lessons of disclosure from female preadolescent and
      adolescent survivors of sexual abuse.
AB  - OBJECTIVES: To enhance understanding of the sexual abuse disclosure process from
      the perspective of preteen and teenage survivors. To reconsider prominent models
      of the disclosure process in light of our findings. METHODS: We conducted a
      secondary analysis of data from four focus groups in which 34 preadolescent and
      adolescent female survivors of sexual abuse had been asked about their treatment
      experiences. Girls often recounted disclosing their victimization to others.
      Using the disclosure segment as our unit of analysis, we isolated 106 for study.
      During analysis, we wrote narrative summaries of each segment's significance,
      grouped these conceptually, and examined their interconnectedness. When
      synthesized, individual experiences of disclosing contributed to understanding
      the overall disclosure process. RESULTS: Three phases were identified: Self,
      where children come to understand victimization internally; Confidant Selection
      Reaction, where they select a time, place, and person to tell and then weather
      that person's reaction (supportive or hostile); and Consequences (good and bad)
      that continued to inform their on-going strategies of telling. The actions and
      reactions of adults were significant and informed the girls' decisions.
      CONCLUSIONS: We advocate integrating existing theories and research into a model
      which views the disclosure process from the child's perspective and includes pre
      disclosure and a post-initial public disclosure stages. The model conceptualizes
      disclosure as an iterative process in which children interact with adults and
      incorporate responses into their on-going decisions about telling (recant, deny,
      affirm, etc.). The combined model should recognize the concerns and position of
      adults as well as the perspective and logic of youth.

PMID- 16289688
TI  - Perpetrator accounts in infant abusive head trauma brought about by a shaking
      event.
AB  - OBJECTIVE: To analyze perpetrator and medical evidence collected during
      investigations of infant abusive head trauma (IAHT), with a view to (a)
      identifying cases where injuries were induced by shaking in the absence of any
      impact and (b) documenting the response of infant victims to a violent shaking
      event. METHOD: A retrospective study was undertaken of IAHT cases investigated by
      the Queensland Police Service over a 10-year period. Cases of head trauma
      involving subdural and/or subarachnoid hematoma and retinal hemorrhages, in the
      absence of any evidence of impact, were defined as shaking-induced. Perpetrator
      statements were then examined for further evidence to support the shaking
      hypothesis and for descriptions of the victim's immediate response to a shaking
      event. RESULTS: From a total of 52 serious IAHT cases, 13 (25%) were found to
      have no medical or observer evidence of impact. In 5 of those 13 cases, there was
      a statement by the perpetrator to the effect that the victim was subjected to a
      shaking event. In several cases both with and without evidence of associated
      impact, perpetrator accounts described an immediate neurological response on the
      part of the victim. CONCLUSION: The study confirms that IAHT resulting in death
      or serious neurological impairment can be induced by shaking alone. In cases
      where the infant's medical condition was adequately described, the symptoms of
      head injury presented immediately.

PMID- 16289691
TI  - Correlates of depression among runaway adolescents in Korea.

PMID- 16289692
TI  - The genetics of generalized vitiligo and associated autoimmune diseases.
AB  - Generalized vitiligo is an acquired disorder in which patches of depigmented
      skin, overlying hair, and oral mucosa result from progressive autoimmune loss of
      melanocytes from the involved areas. Although vitiligo is perhaps the most common
      pigmentary disorder, insufficiently clear clinical definition of the disorder and
      lack of a good laboratory animal model have inhibited progress in understanding
      its pathobiology, its environmental triggers, and in developing specific and
      effective therapeutic approaches. Vitiligo results from a complex interaction of
      environmental, genetic, and immunologic factors, which ultimately contribute to
      melanocyte destruction, resulting in the characteristic depigmented lesions. In
      the past few years, studies of the genetic epidemiology of generalized vitiligo
      have led to the recognition that vitiligo is part of a broader, genetically
      determined, autoimmune/autoinflammatory diathesis. Attempts to identify genes
      involved in vitiligo susceptibility have involved both allelic association
      studies of candidate genes and genome-wide linkage analyses to discover new
      genes, and these studies have begun to shed light on the mechanisms of vitiligo
      pathogenesis. It is anticipated that the discovery of biological pathways of
      vitiligo pathogenesis will provide novel therapeutic and prophylactic targets for
      future approaches to the treatment and prevention of vitiligo and its associated
      autoimmune diseases.

PMID- 16289693
TI  - Prevalence and clinical characteristics of anti-Mi-2 antibodies in Japanese
      patients with dermatomyositis.

PMID- 16289695
TI  - PCBs and organochlorine pesticides (OCPs) in edible fish and shellfish from
      China.
AB  - A wide variety of fish and shellfish were collected from local supermarkets of
      Dalian, Tianjin and Shanghai in China and analyzed for the concentrations of
      polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) such as
      hexachlorobenzene (HCB), hexachlorocyclohexane isomers (HCHs), chlordane
      compounds (CHLs, including trans-chlordane, cis-chlordane, trans-nonachlor and
      cis-nonachlor) and dichlorodiphenyltrichloroethane (DDT) and its metabolites
      (DDTs, including o,p'-DDE, p,p'-DDE, o,p'-DDD, p,p'-DDD, o,p'-DDT and p,p'-DDT).
      Concentrations of PCBs in samples collected from Dalian, Tianjin and Shanghai
      ranged from 1.11 to 8.04 ng/g, 1.26 to 5.60 ng/g and 0.83 to 11.4 ng/g on wet
      weight basis, respectively. The concentrations were lower compared to those in
      developed countries such as Japan and Italy. Average concentrations of HCB, HCHs,
      CHLs and DDTs were 0.38, 0.92, 0.47 and 28.9 ng/g on wet weight basis,
      respectively. The daily intake of PCBs and organochlorine pesticides ingested by
      people living in these cities in China through fish and shellfish was estimated
      and compared with those observed in other areas.

PMID- 16289694
TI  - Knock down of p53 levels in human keratinocytes increases susceptibility to type
      I and type II interferon-induced apoptosis mediated by a TRAIL dependent pathway.
AB  - BACKGROUND: Keratinocytes (KCs) in healthy skin only undergo death following
      differentiation to produce stratum corneum. By contrast, in inflammatory
      pathological conditions featuring type I (IFN-alpha) and type II (IFN-gamma)
      interferons KCs undergo premature apoptosis. OBJECTIVE: To define apoptotic
      susceptibility of KCs, response to interferons was examined. Since molecular
      cross-talk occurs between interferons and p53, potential mechanistic roles for
      p53 in KC apoptosis were investigated. METHODS: Knock down of p53 was performed,
      and apoptotic response to addition of interferons was assessed using FACS and by
      staining for activated caspase 3 and TUNEL. Elucidation of death pathway was
      accomplished by using a dominant negative death receptor construct and a
      neutralizing TRAIL antibody. RESULTS: Reduction in p53 levels in KCs by siRNA
      treatment enhanced, rather than reduced, apoptotic responses to IFN-alpha plus
      IFN-gamma. In an immortalized human KC cell line (HaCaT cells with both p53
      alleles mutated) enhanced apoptotic susceptibility to interferon exposure was
      also observed. The mechanism for this enhanced apoptosis involved induction of
      TRAIL and its interaction with death receptors, as blocking the death receptor
      pathway using dominant negative FADD, or by addition of neutralizing antibody
      against TRAIL, reduced the apoptotic response to IFN-alpha and IFN-gamma.
      CONCLUSION: These results indicate IFN-alpha plus IFN-gamma triggers apoptosis
      independent of p53 in HaCaT cells, and also demonstrate an unexpected survival
      role for p53 in human KCs as regards apoptotic responsiveness to cytokines such
      as IFN-alpha and IFN-gamma involving activation of TRAIL-related death receptors.
      Strategies enhancing p53 regulated survival proteins in KCs may be of therapeutic
      benefit in skin disorders characterized by activated immunocytes triggering
      premature KC apoptosis.

PMID- 16289696
TI  - Effects of the antimicrobial agent sulfamethazine on metolachlor persistence and
      sorption in soil.
AB  - Recent monitoring investigations have shown that antimicrobial agents used in
      veterinary medicine can cause non-point source contamination of soils through
      manure spreading. In the present study, the effect of the antimicrobial agent
      sulfamethazine (sulfadimidine) on degradation and sorption of the herbicide
      metolachlor in a sandy loam soil was studied. In soil samples treated with
      sulfamethazine at two concentrations (15 and 150 microg kg(-1) soil), metolachlor
      persistence was not different than of that observed in untreated samples. These
      results were supported by the absence of effects of both sulfamethazine
      concentration levels on the size of the culturable soil bacteria population.
      Equilibrating soil samples with metolachlor solutions containing equivalent
      sulfamethazine concentrations did not lead to any significant effects on
      metolachlor sorption, suggesting that, under the conditions of the present
      experiment, sulfamethazine did not affect metolachlor bioavailability in soil.
      This laboratory investigation showed that concentrations of sulfamethazine in the
      microg kg(-1) range did not cause significant effects on metolachlor degradation
      and sorption thus not affecting the main processes ruling its environmental fate
      in soil.

PMID- 16289697
TI  - Development of a sandwich enzyme-linked immunosorbant assay for the
      quantification of vitellogeinin in Bullfrog (Rana catesbeiana).
AB  - A sandwich enzyme-linked immunosorbant assay (ELISA) was developed to
      quantitatively detect Bullfrog (Rana catesbeiana) vitellogenin (VTG) levels. This
      procedure involved a sandwich ELISA using monoclonal antibodies of BVmA1 and
      BVmA2 against Bullfrog-VTG, and BVmA1 conjugated to horseradish peroxidase as the
      detection antibody. The assay range was between 9.4 ng/ml and 1200 ng/ml and the
      recovery of the VTG added to Bullfrog control male serum was 92.0-108.8%. Male
      Bullfrog was induced by injection 17beta-estradiol (E2) for four weeks and
      Bullfrog-VTG levels were measured each week. Histological analysis was performed
      for investigating the correlation of the effect to male reproduction and Bullfrog
      VTG level variation depending on E2 dose. After two weeks of E2 exposure, the
      induced Bullfrog-VTG level was significantly higher than Bullfrog control female
      (p<0.05). After four weeks of E2 exposure, the rupture and fusion of seminiferous
      tubule in the testes of male Bullfrog were shown and provided direct evidence
      that the reproduction of male Bullfrog was affected by estrogenic compounds.
      Bullfrog-VTG bioassay, using the sandwich ELISA, could be a sensitive and useful
      tool for quantification of estrogenic principles in aquatic environments.

PMID- 16289698
TI  - Degradation of di-butyl-phthalate by soil bacteria.
AB  - Twelve Gram-positive phthalate ester degraders were isolated from soil. Using
      Biolog GP2 plates, eight of them were identified as belonging to the
      Corynebacterium-Mycobacterium-Nocardia group, while the remaining four were
      unidentifiable. When cultured in the presence of di-butyl-phthalate (DBP) in
      basal salts solution, five of these isolates accomplished more than 90% of DBP
      degradation within 48 h (fast group), three were placed in the medium group, and
      the remaining four were placed in the slow group which caused less than 30% of
      DBP degradation within the same period of time. A 420 bp DNA fragment was
      amplified from six isolates and none of them fell within the slow group. When
      compared with the large subunit of phthalate dioxygenase gene (phtA) of
      Arthrobacter keyseri, 83% and 91% similarities were evident in the nucleotide and
      amino acid sequences, respectively. However, no correlation between cell surface
      hydrophobicity and phthalate degradation ability was evident. Six surfactants
      (Brij 30, Brij 35, Tergitoltype NP-10, Triton N-101, Triton X-100 and SDS) were
      tested for their abilities to increase degradation rate. When added at the
      critical micellar concentration (CMC), they all displayed strong growth
      inhibition against the three bacteria tested, with Brij 30 been the least toxic
      to isolates G2 and G11, and Brij 35 had the least inhibitory effect for G1. When
      half the CMC of Brij 30 was incorporated into the basal salts, the inhibitory
      effect on DBP degradation remained. Soil helped to minimize surfactant toxicity
      of surfactant and increase the degradation potential of some of the test
      bacteria. When DBP-amended soil had been aged for three months, decreases in
      bioavailability were observed but the effect varied tremendously between
      different organisms. For isolates G1, G2, G5, G7 and G17 the aging effects were
      almost non-exist. The present study indicates that selection of a suitable
      degrader may minimize the undesired effect of aging on bioremediation process.

PMID- 16289699
TI  - Organochlorine concentrations, reproductive physiology, and immune function in
      unique populations of freshwater Atlantic stingrays (Dasyatis sabina) from
      Florida's St. Johns River.
AB  - Within the past decade, reproductive and health disorders have been reported to
      occur in unique populations of Atlantic stingrays (Dasyatis sabina) inhabiting
      certain components of Florida's St. Johns River. Since these irregularities are
      consistent with the alleged effects of organochlorine (OC) contaminant exposure
      in other Florida wildlife, the goal of this study was to examine possible
      associations between OC concentrations and reproduction and/or immune function in
      stingrays from this river system. Liver concentrations of 30 OC
      pesticides/pesticide metabolites and total polychlorinated biphenyls (PCBs) were
      measured and compared in D. sabina collected from four central Florida lakes of
      the St. Johns River: Lake George, Lake Harney, Lake Jesup, and Lake Monroe.
      Reproductive biology, serum testosterone and 17beta-estradiol concentrations, and
      circulating white blood cell counts were examined and compared in stingrays from
      lakes that were determined to contain low (Lake George), intermediate (Lake
      Monroe), and high (Lake Jesup) levels of pesticide contamination, based on the
      results of liver OC assessments. Successful breeding occurred in Lake Jesup
      stingrays, indicating that the degree of OC accumulation in these animals is not
      high enough to cause reproductive impairment. However, elevated serum steroid
      concentrations and white blood cell counts were observed in Lake Jesup stingrays,
      suggesting that endocrine and immune function may be altered in these animals due
      to OC exposure and/or other, as yet unknown, ecological factors. Inconsistencies
      in the reproductive success of Lake Monroe stingrays were observed, confirming
      earlier reports of reproductive complications in this sub-population. Based on
      these findings, previous occurrences of reproductive failure in St. Johns River
      stingrays may be due to environmental factors other than OC exposure.

PMID- 16289700
TI  - Organophosphorus pollutants (OPP) in aquatic environment at Damietta Governorate,
      Egypt: implications for monitoring and biomarker responses.
AB  - The study was carried out from spring 1999 to spring 2001 to monitor the residue
      levels of organophosphorus pollutants (OPP) in aquatic environment of the
      drainage canal surrounding a pesticide factory at Damietta Governorate. Water,
      sediment, and fish samples were collected at six different seasonal periods. OPPs
      were analyzed by GLC and confirmed using GC-MS. Chlorpyrifos, chlorpyrifos
      methyl, malathion, diazinon, pirimiphos-methyl and profenofos were detected in
      most samples. Chlorpyrifos was dominant in all water and sediment samples. It was
      ranged from 24.5 to 303.8 and 0.9 to 303.8 ppb in water and sediment samples,
      respectively. Diazinon level was slightly similar to chlorpyrifos in fish
      samples. Data based on the grand total concentration of OPP showed that the most
      polluted samples were collected either at spring 1999 or autumn 2000. They were
      675.5 and 303.8 ppb in water samples and 43.0 and 52.2 ppb in fish collected at
      spring 1999 and autumn 2000, respectively. The obtained results are in parallel
      to that found in case of cholinesterase activity where the activity of both
      acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was declined at
      these seasonal period. The activity levels of AChE and BuChE were found to be
      77.18% and 59.67% of control at spring 1999 and 78.62% and 85.80% of control, at
      autumn 2000, respectively. Thus, AChE and BuChE could be used as biomarkers for
      tracing and biomonitoring OPP pollution.

PMID- 16289701
TI  - Intracellular production of a soluble and functional monomeric streptavidin in
      Escherichia coli and its application for affinity purification of biotinylated
      proteins.
AB  - Monomeric forms of avidin and streptavidin [(strept)avidin] have many potential
      applications. However, generation of monomeric (strept)avidin in sufficient
      quantity is a major limiting factor. We report the successful intracellular
      production of an improved version of monomeric streptavidin (M4) in a soluble and
      functional state at a level of approximately 70 mg/L of an Escherichia coli shake
      flask culture. It could be affinity purified in one step using biotin agarose
      with 70% recovery. BIAcore biosensor analysis using biotinylated bovine serum
      albumin confirmed its desirable kinetic properties. Two biotinylated proteins
      with different degrees of biotinylation (5.5 and 1 biotin per protein) pre-mixed
      with cellular extracts from Bacillus subtilis were used to examine the use of M4
      agarose in affinity purification of protein. Both biotinylated proteins could be
      purified in high purity with 75-80% recovery. With the mild elution and matrix
      regeneration conditions, the M4-agarose had been reused four times without any
      detectable loss of binding capability. The relatively high-level overproduction
      and easy purification of M4, excellent kinetic properties with biotinylated
      proteins and mild procedure for protein purification make vital advancements in
      cost-effective preparation of monomeric streptavidin affinity matrix with
      desirable properties for purification of biotinylated molecules.

PMID- 16289702
TI  - An improved method for fast, robust, and seamless integration of DNA fragments
      into multiple plasmids.
AB  - We describe an improved, universal method for the seamless integration of DNA
      fragments into plasmids at any desired position. The protocol allows in vitro
      joining of insert and linearized plasmid at terminal homology regions using the
      BD In-Fusion cloning system. According to the standard BD In-Fusion protocol,
      vectors are linearized by restriction enzyme digestion. Linearization of plasmids
      by polymerase chain reaction (PCR), instead of restriction enzyme digestion,
      extends the usefulness of the method by rendering it independent of restriction
      endonuclease recognition sites and by allowing seamless insertion of DNA
      fragments at any position, without introduction of unwanted nucleotides flanking
      the site of insertion. The combination of PCR linearization of plasmids and BD In
      Fusion technology has shown to be very useful for the insertion of genes into the
      expression regions of multiple plasmids for the heterologous expression of
      proteins in Escherichia coli. Hands-on time is minimal and there is no need for
      preparative gel electrophoresis. The protocol is very simple and only involves
      PCR and liquid handling steps. The method should therefore theoretically have a
      good potential for automation.

PMID- 16289703
TI  - Overexpression and purification of scytovirin, a potent, novel anti-HIV protein
      from the cultured cyanobacterium Scytonema varium.
AB  - Scytovirin (SVN) is a novel anti-human immunodeficiency virus (HIV) protein
      isolated from aqueous extracts of the cultured cyanobacterium Scytonema varium.
      The protein consists of a single 95-amino acid chain with significant internal
      sequence duplication and 10 cysteines forming five intrachain disulfide bonds. A
      synthetic gene that encodes scytovirin was constructed, and expressed in
      Escherichia coli, with thioredoxin (TRX) fused to its N-terminus (TRX-SVN). Most
      of the expressed protein was in soluble form, which was purified by a
      polyhistidine tag affinity purification step. SVN was then cleaved from TRX with
      enterokinase and separated from the TRX partner by C18 reversed-phase HPLC. This
      production method has proven superior to earlier synthetic attempts and
      recombinant procedures using a standard expression system. The current system
      resulted in yields of 5-10mg/L of purified SVN for structural studies and for
      preclinical development of SVN as a topical microbicide for HIV prophylaxis.

PMID- 16289704
TI  - Construction of an inducible, pfkA and pfkB deficient strain of Escherichia coli
      for the expression and purification of phosphofructokinase from bacterial
      sources.
AB  - As the key obligatory step in the glycolytic pathway, the regulation of
      phosphofructokinase (PFK-1) has been the focus of study of several laboratories.
      While standard cloning procedures have opened the door to study PFK from a vast
      array of sources, a good pfk knockout Escherichia coli strain has not previously
      been developed. Many laboratories rely on DF1020 or similar derivatives for PFK
      expression. Unfortunately, DF1020 grows poorly and does not have an inherent
      means for controlling expression of genes from plasmids. More importantly,
      however, DF1020 has a tendency to grow on minimal media when glucose is used as
      the sole carbon source. In this study, a new E. coli PFK expression strain
      lacking both PFK-1 and PFK-2 has been engineered using lambda-red mediated
      chromosomal deletion. The resulting strain has been designated RL257. In addition
      to having both pfkA and pfkB deleted, RL257 contains the lacI(q) allele, which
      allows for inducible expression when coupled with an expression vector containing
      either the lac or tac promoter.

PMID- 16289705
TI  - An efficient mammalian cell-free translation system supplemented with translation
      factors.
AB  - Development of an efficient cell-free translation system from mammalian cells is
      an important goal. We examined whether supplementation of HeLa cell extracts with
      any translation initiation factor or translational regulator could enhance
      protein synthesis. eIF2 (eukaryotic translation initiation factor 2) and eIF2B
      augmented translation of capped, uncapped and encephalomyocarditis virus-internal
      ribosome entry site-promoted mRNAs. eIF4E specifically stimulated capped mRNA
      translation, while p97, a homologue to the C-terminal two-thirds of eIF4G,
      increased uncapped mRNA translation. When the HeLa cell extract was supplemented
      with a combination of eIF2, eIF2B, and p97, the capacity to synthesize a protein
      from an uncapped mRNA became comparable to that from the capped counterpart
      stimulated with a combination of eIF2, eIF2B, and eIF4E. A dialysis method
      rendered the HeLa cell extract capable of synthesizing proteins for 36h, and the
      yield was augmented when supplemented with initiation factors. In contrast, the
      productivity of a rabbit reticulocyte lysate was not enhanced by this method.
      Collectively, the translation factor-supplemented HeLa cell extract should become
      an important tool for the production of recombinant proteins.

PMID- 16289706
TI  - Rapid and sensitive liquid chromatography-mass spectrometry method for
      determination of ropinirole in human plasma.
AB  - A rapid and robust liquid chromatography-mass spectrometry (LC-MS/MS) method was
      developed for non-ergoline dopamine D(2)-receptor agonist, ropinirole in human
      plasma using Es-citalopram oxalate as an internal standard. The method involves
      solid phase extraction from plasma, reversed-phase simple isocratic
      chromatographic conditions and mass spectrometric detection that enables a
      detection limit at picogram levels. The proposed method was validated with linear
      range of 20-1,200 pg/ml. The extraction recoveries for ropinirole and internal
      standard were 90.45 and 65.42%, respectively. The R.S.D.% of intra-day and inter
      day assay was lower than 15%. For its sensitivity and reliability, the proposed
      method is particularly suitable for pharmacokinetic studies.

PMID- 16289707
TI  - Multiple antigen concentrations in delayed-type hypersensitivity (DTH) and
      response diversity during and after immunization with a peptide-based HIV-1
      immunotherapy candidate (Vacc-4x).
AB  - Delayed-type hypersensitivity (DTH) testing represents a simple in vivo method
      for monitoring cellular immune responses. In a phase II clinical trial on HIV
      infected patients (n = 38) of the peptide-based HIV-1 immunotherapy candidate
      Vacc-4x, we monitored DTH responses to three antigen concentrations of Vacc-4x.
      We have shown that DTH can be used quantitatively to measure immune reactions to
      Vacc-4x and its individual peptide components. Our data stress the qualities and
      differences of induration and erythema, both in discriminating individual
      antigens and in monitoring immunizations over time. The data also indicate that
      DTH baseline-status might have important impact on immunization kinetics.

PMID- 16289708
TI  - Immunization with a DNA chimeric molecule encoding a hemagglutinin peptide and a
      scFv CD21-specific antibody fragment induces long-lasting IgM and CTL responses
      to influenza virus.
AB  - Killed viral vaccines are known to induce primarily antibody responses. By
      contrast DNA vaccination using naked DNA encoding viral antigens induces both
      humoral and cellular immune responses. Various approaches have been used to
      construct DNA vaccines with build-in adjuvanticity. We hypothesized that
      sequences encoding a common epitope of influenza A virus hemagglutinin jointed to
      sequences encoding a single-chain variable fragment (scFv) antibody fragment to a
      costimulatory B cell surface receptor would result in the in vivo expression of a
      chimeric viral peptide with increased immunogenicity. Such a hybrid DNA molecule
      was constructed by us, encoding a T and B cell epitope-containing influenza
      hemagglutinin peptide and a scFv antibody fragment binding to mouse complement
      receptors I and II (CR1 and CR2). A single immunization with a plasmid containing
      the described construct induced a strong anti-influenza cytotoxic response
      lasting for more than six months and a weak antibody response.

PMID- 16289709
TI  - Comparison of immune responses after intra-typic heterologous and homologous
      vaccination against foot-and-mouth disease virus infection in pigs.
AB  - This study compares the immune responses and protection induced by intra-typic
      heterologous vaccination with that induced by homologous vaccination against
      challenge with foot-and-mouth disease virus (FMDV). Humoral and cell-mediated
      immune responses and protection against challenge with FMDV O Taiwan were
      examined in a non-vaccinated group, a group vaccinated with O Taiwan FMD vaccine
      and a group vaccinated with O Manisa FMD vaccine. Five pigs from each group were
      challenged with FMDV type O Taiwan 14 days after vaccination and five other pigs
      were contact-exposed to the inoculated pigs. Both homologous and heterologous
      vaccination protected against challenge with FMDV O Taiwan at 2 weeks after
      vaccination. In the heterologous vaccinated group, cross-neutralizing antibody
      titres against O Taiwan could be detected although the ratio 'r(1)' was 0.4,
      which was significantly smaller than the critical r-value. Cell-mediated immune
      responses were detected after both homologous and heterologous vaccination. Virus
      induced in vitro lymphocyte (cross-) proliferation and production of both a Th1
      type (IFN-gamma) and a Th2-type (IL-10) cytokine response were demonstrated in
      cultures of peripheral blood mononuclear cells (PBMC). The findings show that
      heterologous (emergency) vaccination can prevent clinical disease and shedding of
      virus. The induction of the cell-mediated immune responses after (heterologous)
      vaccination needs more research but data on these responses might provide
      additional tools for both vaccine choice and vaccine development.

PMID- 16289710
TI  - Susceptibility of Streptococcus pneumoniae to penicillin, azithromycin and
      telithromycin (PROTEKT 1999-2003).
AB  - Isolates of Streptococcus pneumoniae collected over the first 4 years of the
      PROTEKT study were tested for susceptibility to penicillin, azithromycin and
      telithromycin. A total of 20,750 isolates were collected from 39 countries.
      Penicillin non-susceptibility rates were stable over the study period; overall,
      21.8% of isolates were resistant. Azithromycin resistance increased from 31.0% in
      Year 1 to 36.3% in Year 4. Resistance rates for penicillin and azithromycin
      varied between countries and were highest in France, Spain, South Africa, USA and
      the Far East. Multidrug resistance in S. pneumoniae did not change significantly
      over the 4 years, with an overall rate of 38.6%. Telithromycin retained good
      activity against S. pneumoniae (0.1% of isolates resistant), including multidrug
      resistant isolates.

PMID- 16289712
TI  - Effects of wrist position and contraction on wrist flexors H-reflex, and its
      functional implications.
AB  - In order to determine whether joint position exerts a powerful influence on
      length-tension regulation in multiarticulate wrist flexors, three wrist positions
      (neutral, flexion and extension) and four levels of flexor contraction [0%, 10%,
      20% and 30% maximum voluntary contraction (MVC)] were manipulated. There were
      significant differences in H-reflex amplitudes according to wrist positions and
      levels of flexor contraction. H-reflex increased linearly as a function of
      contraction in all three wrist positions. H-reflex was consistently larger in the
      wrist flexion than in the wrist extension position. The strength of the
      relationship (omega2) indicated that wrist position had a greater effect on H
      reflex than force of muscle contraction. The interaction between wrist flexors
      contraction and joint position was significant only in the wrist flexion
      position. Trend analysis showed that, in the wrist flexion position, a low level
      of contraction was sufficient to maximally facilitate the H-reflex; however, a
      quadratic component was seen at higher contraction levels. The above findings may
      reflect the length-tension relationship of the multiarticulate wrist flexors.
      Therefore, this paper will discuss the functional implications related to the
      larger H-reflex in flexion position and the depressed H-reflex in the wrist
      extension position.

PMID- 16289711
TI  - Low-dose aerosol model of pneumococcal pneumonia in the mouse: utility for
      evaluation of antimicrobial efficacy.
AB  - Current mouse models of pneumococcal infection have two disadvantages: (1) those
      that are not based on lung infections do not take into account the tissue
      pharmacokinetics of drugs in the lung parenchyma; and (2) those that are
      pneumonia models typically use large infectious doses to produce fulminant
      infections. The objective of this study was to determine the utility of a low
      dose aerosol pneumonia model for evaluation of antimicrobial efficacy. Mice
      infected with penicillin-susceptible or non-susceptible pneumococci were left
      untreated or treated for 2.5 days with ertapenem in a range of doses. Efficacy
      was determined by the change in log10 colony-forming unit (CFU) counts and
      survival. Low-dose aerosol infection with the penicillin-susceptible strain 6303
      produced an indolent pneumonia that was reliably lethal 1-2 weeks after
      infection. Ertapenem demonstrated bactericidal activity and prevented mortality
      over a range of doses after infection with strain 6303, but demonstrated only
      bacteriostatic activity at the highest doses used against the more resistant 1980
      strain. A beneficial effect on survival was seen at doses approaching
      bioequivalence with the standard human dosage. The low-dose aerosol model of
      pneumococcal pneumonia in the mouse is a viable alternative model for the
      evaluation of antimicrobial efficacy. It may be particularly useful in the
      evaluation of drugs that concentrate in the alveolar epithelial lining fluid or
      lung parenchyma.

PMID- 16289713
TI  - Mucilaginous aggregates in the northern Adriatic in the period 1999-2002:
      typology and distribution.
AB  - The spatial and temporal distributions of different types of visible mucilaginous
      aggregates were investigated monthly by underwater video cameras in the northern
      Adriatic (NA) from June 1999 to July 2002. Small aggregates (flocs, macroflocs
      and stringers) were observed in all seasons with higher values in autumn and
      winter. Larger aggregates (ribbons, cobwebs, clouds, and false bottoms) formed
      only during late-spring and summer, particularly in 2000 and 2002, when the
      seasonal thermohaline stratification was marked. In fact, the process of mucilage
      formation took place mainly in the upper water column, above the main pycnocline.
      The spatial distribution shows that higher concentrations of small aggregates
      occur in the more productive coastal waters. The larger aggregates form or
      accumulate mainly in coastal waters in the southern part of the NA and in the
      central part of the Po River delta-Rovinj transect, where a gyre greatly
      influences the aggregates distribution. The fronts between low salinity coastal
      waters and high salinity waters of southern origin play an important role for
      accumulation and aggregation of the mucilage during spring and summer. Most of
      the aggregates accumulate in correspondence with strong pycnoclines with
      differences in density anomaly of 2 kg m(-3) or higher. False bottoms formed in
      correspondence with strong haloclines (DeltaS congruent with 2), while cobwebs
      and ribbons also occurred when the halocline was less marked (DeltaS<0.5).
      Meteorological conditions greatly influenced the aggregate formation. Calm
      weather and weak winds favour aggregation processes, while strong north-easterly
      winds, causing intense mixing, result in the dispersion of the mucilaginous
      aggregates, as occurred during the Bora event in July 2000.

PMID- 16289714
TI  - Malignant extraovarian endometriosis: a review.
AB  - AIMS: Malignant transformation in extra-ovarian endometriosis is a rare but known
      complication. This distinct pathological entity is reviewed with a specific focus
      on aetiology and treatment. METHODS: Studies were identified by searching the
      English language literature in the MEDLINE database and by an extensive review of
      bibliographies from articles found through that search. FINDINGS: Up to 1% of
      women with endometriosis will develop endometriosis-associated neoplasm. Almost a
      quarter of the reported cases of malignancy in endometriosis have involved extra
      ovarian tissues. In many cases, hormonal factors may play a role in its
      pathogenesis. Estrogen monotherapy in obese patients significantly increase the
      risk of malignant extra-gonadal endometrial transformation. Genetic anomalies
      have also been reported such as loss of heterozygosity on chromosome 5q. For
      patients with disease confined to the site of origin, a 82-100% 5-year survival
      has been noted for endometrioid cell type; disseminated intraperitoneal disease,
      however, has a very poor associated prognosis, with a 0-12% 5-year survival
      overall. CONCLUSIONS: Women with endometriosis-associated cancers most likely
      represent a different class of patients than traditional ovarian cancer patients
      and may require different therapeutic options.

PMID- 16289715
TI  - The free vastus lateralis flap for reconstruction in ablative oncologic head and
      neck surgery.
AB  - AIMS: The vastus lateralis muscle is an accessory extensor for the knee suitable
      as a free myocutaneous flap in reconstructive head and neck surgery. We report
      the use of this muscle as a flap. METHODS: We have used the free myocutaneous
      vastus lateralis flap for reconstruction following ablative head and neck tumour
      surgery in six patients. The clinical outcome, time of surgery for flap
      preparation and anatomosis, follow-up and functional outcome were analysed.
      RESULTS: Five of our patients showed a very satisfactory functional and cosmetic
      outcome. Post-operatively, there was no prolonged immobilisation and no
      limitation of movement to the hip and knee. No unfavourable side-effects at the
      donor side were noted. CONCLUSIONS: We find this flap a very useful addition to
      our free myocutaneous flap armamentarium. It has a specific suitability for
      replacing large defects.

PMID- 16289716
TI  - Hyperthermic isolated limb perfusion (HILP) in malignant melanoma. Experience
      with 101 patients.
AB  - AIMS: To analyse results with a standardized HILP procedure in terms of response
      rate, recurrence pattern and complication rate. PATIENTS AND METHODS: From 1992
      to 2003 HILP with melphalan and dactinomycin was performed in 101 patients with
      loco-regional metastases of malignant melanoma of the limbs. Among these were 66
      women and 35 men with a median age of 62 years. Forty patients were in M. D.
      Anderson stage IIIA, 51 patients in stage IIIAB and 9 had stage IV disease at the
      time of perfusion. If not been done before, regional lymph node dissection
      preceded limb perfusion in the same setting. RESULTS: A complete response (CR)
      was observed in 58 out of 87 evaluable patients. Twenty-one patients achieved a
      partial response (PR) and eight patients were non-responders. The overall
      response rate was 90.8%. The median recurrence-free interval after CR was 21
      months. Severe toxicity (Wieberdink IV/V) was observed in five patients
      necessitating fasciotomy in four of them and above knee amputation in one
      patient. All further cases presented with grade II-III toxicity. The overall
      survival was 42 months, with a 5-year survival rate of 38%. Survival
      significantly differed according to stage of disease. CONCLUSION: HILP is an
      effective treatment for loco-regional tumour relapse of malignant melanoma of the
      extremities and has improved by modification of technique. In the absence of
      regional lymph node and distant metastases long-term survival can be achieved in
      responders.

PMID- 16289717
TI  - Endovascular isolated hepatic perfusion under pneumoperitoneum.
AB  - AIMS: Isolated hepatic perfusion (IHP) allows loco-regional administration of
      high drug doses for cancer treatment. Minimally invasive endovascular occlusion
      techniques can be used for IHP, but control of leakage remains a major drawback.
      We hypothesized that the increased intraabdominal pressure generated by a CO(2)
      pneumoperitoneum (PP) can reduce the leakage rate of hypoxic endovascular IHP by
      mechanical compression of the capillary beds connecting the liver to the systemic
      circulation. METHODS: IHP was performed on adult pigs through laparotomy using a
      fenestrated double balloon-catheter placed into the retrohepatic vena cava to
      collect the hepatic outflow which was reinfused into the hepatic artery through
      an extracorporeal circulation system. Each pig underwent IHP during four
      consecutive phases: abdomen open (Phase I), abdomen closed under a 15 and 20 mmHg
      pneumoperitoneum (Phase II and III, respectively) and abdomen re-opened (Phase
      IV). The leakage rate from the liver to the systemic circulation was continuously
      monitored using a nuclear medicine technique. The systemic arterial pressure, the
      IHP inflow and outflow pressures and the flow rate were recorded. RESULTS:
      Leakage from the hepatic extracorporeal circulation to the systemic circulation
      occurred in all animals during Phase I. Under PP (Phases II and III), two leakage
      profiles were observed: (1) a major increase of the leakage rate in two animals
      with a high differential pressure (>50 mmHg) between the IHP inflow and the
      systemic pressures; (2) no change or a decrease of the leakage rate in the other
      three animals who had a low or negative differential pressure (<30 mmHg). Leakage
      was undetectable in all animals after exsufflation of the PP (Phase IV).
      CONCLUSIONS: IHP under PP is feasible. Leakage is not reduced during PP. A high
      gradient between the IHP inflow and the systemic pressure increases systemic
      leakage during PP. Upon release of the PP, the leakage is most likely redirected
      towards the volume depleted low resistance portal territory.

PMID- 16289719
TI  - Floquet-van Vleck analysis of heteronuclear spin decoupling in solids: the effect
      of spinning and decoupling sidebands on the spectrum.
AB  - We investigate the effect of magic angle spinning on heteronuclear spin
      decoupling in solids. We use an analytical Floquet-van Vleck formalism to derive
      expressions for the powder-averaged signal as a function of time. These
      expressions show that the spectrum consists of a centerband at the isotropic
      frequency of the observed spin, omega(0), and rotational decoupling sidebands at
      omega(0)+/-omega(1)+/-momega(r), where omega(1) is the decoupling field strength
      and omega(r) is the rotation frequency. Rotary resonance occurs when the
      rotational decoupling sidebands overlap with the centerband. Away from the rotary
      resonance conditions, the intensity of the centerband as a function of
      omega(r)/omega(1) is simply related to the total intensity of the rotational
      decoupling sidebands. Notably, in the absence of offset terms it is shown that as
      omega(1) decreases, the centerband intensity can decrease without any associated
      broadening. Furthermore, the centerband width is shown to be independent of
      spinning speed, to second order for the effects we consider. The effects of I
      spin chemical shift anisotropy and homonuclear dipolar couplings are also
      investigated. The analytical results are compared to simulations and experiments.

PMID- 16289720
TI  - Abductor pollicis longus tendon rupture in De Quervain's disease.
AB  - De Quervain's disease is a stenosing tenovaginitis involving the first extensor
      compartment of the wrist. The similarity of its symptomatology to a number of
      other conditions and its controversial aetiology are only a few of the barriers
      which often delay its diagnosis and treatment. We report the first two cases in
      the literature of abductor pollicus longus tendon rupture in patients with De
      Quervain's disease who had been treated with conservative methods. The relevant
      literature is reviewed.

PMID- 16289718
TI  - Pre-operative chemo-radiotherapy improves the sphincter preservation rate in
      patients with rectal cancer located within 3 cm of the anal verge.
AB  - AIMS: To evaluate whether pre-operative chemo-radiotherapy (CRT) improves the
      sphincter preservation rate for distal rectal cancers within 3 cm of the anal
      verge. METHODS: Between January 2001 and December 2004, 49 patients underwent
      surgery with or without pre-operative CRT for primary rectal adenocarcinoma
      within 3 cm of the anal verge. Clinical data were retrospectively reviewed,
      including stage workups, surgical records and pathology records to determine
      sphincter preservation rate and the factors influencing sphincter preservation.
      RESULTS: Of 49 patients with rectal tumours within 3 cm of the anal verge, 31
      underwent pre-operative CRT followed by surgery (CRT group), and 18 underwent
      surgery alone (non-CRT group). Sphincter preservation was possible in 11 of 31
      CRT patients, and only one of 18 non-CRT patients (p=0.036). The factors most
      influencing sphincter preservation were reduction in tumour size (p=0.005) and
      downstaging (p=0.001) following pre-operative CRT. CONCLUSION: We could observe
      that sphincter preservation was improved in CRT group with statistical
      significance when compared to non-CRT group in our study patients with rectal
      cancer within 3 cm of the anal verge.

PMID- 16289721
TI  - Association between scalp hair-whorl direction and hemispheric language
      dominance.
AB  - Asymmetry is a common phenomenon in higher organisms. In humans, the cortical
      representation of language exhibits a high degree of asymmetry with a prevalence
      of about 90% of left hemispheric dominance, the underlying mechanisms of which
      are largely unknown. Another sign that exhibits a form of lateralization is the
      scalp hair-whorl direction, which is either clockwise or anti-clockwise. The
      scalp hair-whorl develops from the same germ layer as the nervous system, the
      ectoderm, between the 10th and 16th week in utero and has been shown to be
      associated with various neurodevelopmental disorders. Here, we use an established
      fMRI paradigm to examine the association of a solely biological marker of
      asymmetry, hair-whorl direction and language lateralization. We show that the
      mechanism that influences hair-whorl direction and handedness [Klar, A.J.S.,
      2003. Human handedness and scalp hair-whorl direction develop from a common
      genetic mechanism. Genetics 1651, 269-276.] also affects cerebral language
      dominance.

PMID- 16289723
TI  - Evaluation of micro-tensile bond strengths of composite materials in comparison
      to their polymerization shrinkage.
AB  - OBJECTIVE: The present study determined the influence of polymerization shrinkage
      of eight commercially available hybrid, micro-filled and nano composites (Z100
      and Filtek Supreme, 3M-ESPE; Charisma and Durafill, Heraeus Kulzer; Tetric and
      InTen-S, Ivoclar Vivadent; Enamel plus HFO, GDF; Palfique Estelite Low Flow,
      Tokuyama) placed in large class 1 cavities on the bond strength to dentin.
      METHODS: Polymerization shrinkage was recorded for 300 s at room temperature with
      a Stress-Strain-Analyzer (C(FACTOR)=0.3). The maximum contraction stresses after
      300 s, the time until gelation (t(0.5 N)) and the coefficient of near linear fit
      of contraction force/time (gradient) were analysed. For the evaluation of the
      micro-tensile-bond-strength (micro-TBS), hourglass shape samples obtained from a
      total of 32 no carious extracted human third and second molars, randomly divided
      into 8 groups, were used. Micro tensile bond strengths were determined by
      computing the ratio of maximum load by the adhesion area of the hourglass shape.
      In order to analyze the quality of the polymerization within fillings, hardness
      profiles of a surface cut thought the middle of the restored tooth and along the
      tooth axis were made. Further, the modulus of elasticity, determined in a three
      point-bending test, as well as the variation of the modulus of elasticity and of
      the hardness within a filling were considered. The statistical analyses were
      conducted by ANOVA (alpha=0.05) and post-hoc Tukey's test. RESULTS: A significant
      correlation between polymerization shrinkage and micro-TBS was found (Pearson; 
      0.44). The correlation between modulus of elasticity in bending test and
      shrinkage stress (Pearson; 0.77), coefficient of near linear fit m (Pearson;
      0.72), time until gelation (Pearson; -0.52) and micro-tensile-bond-strength
      (Pearson; -0.45) was also significant. A high polymerization tension and modulus
      of elasticity negatively affected the adhesion of the composite to the tooth hard
      substance. Further, the number of samples lost during the slice cutting and the
      hourglass shape preparation was found to correlate highly significantly with the
      shrinkage stress (Pearson; 0.97), coefficient of near linear fit m (Pearson;
      0.94) and modulus of elasticity (Pearson; 0.82). All materials showed sufficient
      polymerization within the filling in comparison to the filling surface, the
      hardness at the bottom of the filling was greater than 80% of the maximum
      hardness value. The modulus of elasticity was not considerably reduced within the
      filling. SIGNIFICANCE: High contraction stress and modulus of elasticity, fast
      development of contraction force and an early start of stress build-up of
      materials placed in restrictive cavities cause tension in the material with a
      possible subsequent distortion of the bond to the tooth structure. A low modulus
      of elasticity is not necessarily associated with high bond strength. However, it
      causes a more uniform stress distribution at the restorative composite-tooth
      interface. This is also evident in a reduced sample loss during the different
      stages of sample preparation.

PMID- 16289722
TI  - Post-surface conditioning improves interfacial adhesion in post/core
      restorations.
AB  - OBJECTIVES: To verify the influence of different etching procedures of the post
      surface on microtensile bond strength values between fiber posts and composite
      core materials. METHODS: 60 DT Light Posts were divided into 10 subgroups using
      five different chemical surface treatments and two composite materials to build
      up the abutment. Chemical surface treatments including etching with potassium
      permanganate; treatment with 10% hydrogen peroxide; treatment with 21% sodium
      ethoxide; etching with potassium permanganate and 10 vol.% HCl; silanization
      (control group) were performed on the post's surface. The build-up was performed
      using (A) Core Paste XP (Dent Mat) and (B) Unifil Flow (GC). Two samples of each
      group were randomly selected to investigate the morphologic aspect of the
      post/core interface with a scanning electron microscope (SEM). The remaining
      specimens were cut so as to obtain microtensile sticks that were loaded in
      tension at a cross-head speed of 1mm/min until failure. The statistical analysis
      was performed using two-way ANOVA and the Tukey's test for post-hoc comparisons
      (alpha=0.05). RESULTS: SEM examination showed an interpenetrating adhesion
      network between the treated fiber post-surface and the composite material in all
      the groups tested. The results achieved with potassium permanganate had a
      significant influence on microtensile interfacial bond strength values with both
      the tested materials. Post-superficial treatments enhanced the bond strength
      particularly of Core Paste XP. SIGNIFICANCE: Etching procedures showed a similar
      effect on the post-surface and enhanced the adhesion of composite core build-ups
      as a result of micromechanical and chemical retention.

PMID- 16289724
TI  - The effects of common errors on sealing ability of total-etch adhesives.
AB  - OBJECTIVES: This study evaluated the effect of errors commonly made in using
      total-etch adhesives, on the resulting bond strength, fluid movement and
      nanoleakage of resin dentin bonds. METHODS: Two total-etch adhesives were used
      for bonding to dentin according to the manufacturers' recommendations, with
      meticulous solvent evaporation (control), or with the introduction of common
      bonding errors-wet bonding without solvent evaporation (no evaporation), and dry
      bonding. RESULTS: The 24-hour bond strength of the control was significantly
      higher than the other groups (p <0.05). For all groups, the higher initial
      permeability declined significantly after 24 h. The fluid movement across bonded
      dentin was similar in the control and dry bonding for both adhesives, whereas
      significantly higher permeability (p<0.05) was recorded for the no evaporation
      groups even after 24 h. Extensive silver impregnation within hybrid layers was
      seen by TEM in the no evaporation and dry bonding specimens after 24 h. Dry
      bonding caused collapse of the collagen matrix and interfered with resin
      infiltration. In contrast, inadequate solvent evaporation and/or residual water
      during dentin bonding results in dilution or incomplete polymerization of the
      resin, leading to severe nanoleakage formation. SIGNIFICANCE: Increased
      permeability associated with incomplete solvent evaporation in total-etch
      adhesives may lead to poor bond strength.

PMID- 16289725
TI  - The initiating radical yields and the efficiency of polymerization for various
      dental photoinitiators excited by different light curing units.
AB  - OBJECTIVES: To evaluate the efficiency of the photopolymerization of dental
      resins it is necessary to know to what extent the light emitted by the light
      curing units is absorbed by the photoinitiators. On the other hand, the
      efficiency of the absorbed photons to produce species that launch the
      polymerization process is also of paramount importance. Therefore, the previously
      determined PAE (photon absorption efficiency) is used in conjunction with the
      polymerization quantum yields for the photoinitiators, in order to be able to
      compare the total process on an equivalent basis. This parameter can be used to
      identify the best performance for the photochemical process with specific
      photoinitiators. METHODS: The efficiency of LED (Ultrablue IS) and QTH (Optilux
      401) lamps were tested comparing their performances with the photoinitiators
      camphorquinone (CQ); phenylpropanedione (PPD); monoacylphosphine oxide (Lucirin
      TPO); and bisacylphosphine oxide (Irgacure 819). The extent of
      photopolymerization per absorbed photon was determined from the polymerization
      quantum yields obtained by using the photoinitiators to polymerize methyl
      methacrylate, and afterwards combined with the previously determined PAEs.
      RESULTS: Although CQ presents a rather low polymerization quantum yield, its
      photopolymerization efficiency is practically the highest when irradiated with
      the Ultrablue LED. On the other hand, Lucirin is much more efficient than the
      other photoinitiators when irradiated with a QTH lamp, due to its high quantum
      yield and the overlap between its absorption spectrum and the output of the
      visible lamp light. SIGNIFICANCE: Difference in photopolymerization efficiencies
      arise when combinations of photoinitiators are used, and when LED sources are
      used in preference to QTH. Mechanistic understanding is essential to optimal
      initiator formulation.

PMID- 16289726
TI  - A link between lead and cadmium kinetic speciation in seawater and accumulation
      by the green alga Ulva lactuca.
AB  - In this work, studies on the bioaccumulation of Cd and Pb by Ulva lactuca at
      different sites of Gulf San Jorge (Patagonia, Argentina) are presented. Higher
      values of bioaccumulated Cd were found in Punta Maqueda - a site believed to
      serve as a control - in comparison to those in Punta Borja, a place highly
      exposed to urban and industrial activities. Consequently; the labile fractions of
      Cd and Pb in seawater were determined with a flow injection-preconcentration
      manifold interfaced to a graphite furnace-atomic absorption spectrometer (FI
      GFAAS). The results obtained by kinetic speciation showed that the variable that
      correctly explains heavy metals accumulation in the alga, is the labile metal
      fraction in seawater. We propose to use an enhancement ratio - on the basis of
      the kinetically labile metal fraction - for calculation of the metal accumulated
      by the alga relative to its environment.

PMID- 16289727
TI  - Attentional load of the primary task influences the frontal but not the temporal
      generators of mismatch negativity.
AB  - According to the model hypothesized by Naatanen and Michie, the generation of the
      mismatch negativity (MMN) requires a mismatch detection, taking place in temporal
      areas, followed by the activation of frontal generators, underlying attention
      switching toward the deviant stimulus. We aimed at verifying whether the
      activation of temporal and frontal regions is dependent on the amount of
      attentional resources allocable toward the deviant stimulus. We recorded event
      related potentials (ERPs) in nine healthy subjects while reading and during a
      demanding visual task (Multiple Features Target Cancellation, MFTC). Raw data
      were further evaluated by Brain Electrical Source Analysis (BESA). During the
      Reading condition, distraction toward the unattended auditory stimuli was
      reflected by the enhancement of the N1 response to frequent stimuli and by the
      elicitation of a P3a response to deviant ones. The MMN distribution was explained
      by bilateral temporal dipoles. During the MFTC condition, no P3a was detected,
      while source analysis showed the activation of a right frontal generator.
      Temporal dipoles showed no change between the two conditions: we thus conclude
      that the earlier mismatch detection is independent on the attentional load. By
      contrast, the activation of a right frontal subcomponent occurred only during the
      high-load task, independently on any actual attention shift reflected by the P3a
      component. We thus discuss the hypothesis whether the right frontal MMN
      generator, rather than subserving a simple attention switching toward the deviant
      stimulus, plays a role in modulating the auditory change detection system
      ("contrast enhancement" model).

PMID- 16289728
TI  - [Choice of neurostimulators for locoregional anesthesia].

PMID- 16289729
TI  - Phylogeography of the salamander genus Pseudobranchus in the southeastern United
      States.
AB  - This study provides an extensive set of mitochondrial cytochrome b sequences for
      the salamander genus Pseudobranchus of the southeastern United States. These
      sequences were analysed by multiple phylogenetic methods that support a single
      set of major phylogeographic divisions for its two corroborated species (P.
      axanthus and P. striatus). These phylogeographic divisions overlap with the
      geographic breakpoints of other freshwater and terrestrial taxa in this region.
      Collectively, these overlapping patterns highlight the Central Highland and
      Tifton/Vidalia uplands as a significant barrier to Atlantic vs. Gulf coast
      groups, while reconfirming the phylogeographic significance of the Altamaha and
      Apalachicola river drainages. Despite their distinct phylogeographic split, P.
      striatus from west and east of these uplands are not currently recognizable as
      separate species according to the concordance principles for species definition.

PMID- 16289730
TI  - Aberrations of early trophoblast differentiation predispose to pregnancy failure:
      lessons from the anti-phospholipid syndrome.
AB  - OBJECTIVES: The epithelium of the human placenta comprises an inner
      cytotrophoblast (CT) which proliferates and fuses with the outer differentiated
      syncytiotrophoblast (ST). Turnover has been studied focussing on second and third
      trimester placentas but with a paucity of data describing the normal first
      trimester trophoblast. The aim of this study was to compare the nuclear CT:ST
      ratio in normal and pathological pregnancy and thus establish the relationship
      between cytotrophoblast and syncytiotrophoblast nuclear number during early
      gestation. METHODS: Archival first trimester material from placentas from healthy
      pregnancy and recurrent miscarriage (anti-phospholipid syndrome) was stained with
      H&E, cytokeratin-7 and Mib-1. The area of trophoblast as a fraction of total
      villous area was calculated and the number of sectioned cytotrophoblast and
      syncytiotrophoblast nuclei as well as the number of proliferating cytotrophoblast
      was evaluated. RESULTS: Normal features of trophoblast development during the
      first trimester (rise in trophoblast area, increase in number of
      syncytiotrophoblast nuclei, increase in number of proliferating cytotrophoblast,
      decrease in the nuclear CT:ST ratio) are absent/reversed in tissues from
      recurrent miscarriage (decreasing trophoblast area, constant number of
      syncytiotrophoblast nuclei, decreasing number of proliferating trophoblast,
      constant nuclear CT:ST ratio). CONCLUSIONS: Proliferation of cytotrophoblast in
      early gestation provides a pool of trophoblast stem cells critical for ongoing
      placental development. Premature cytotrophoblast differentiation in favour of
      syncytial fusion results in deficiencies of cytotrophoblast and rarification of
      villous trophoblast. Abnormal trophoblast differentiation in early gestation may
      be due to a premature onset of maternal perfusion of the placenta and may be a
      likely antecedent for conditions associated with failure of placentation such as
      recurrent miscarriage.

PMID- 16289732
TI  - Biosorption of copper(II) and zinc(II) from aqueous solution by Pseudomonas
      putida CZ1.
AB  - To study Pseudomonas putida CZ1, having high tolerance to copper and zinc on the
      removal of toxic metals from aqueous solutions, the biosorption of Cu(II) and
      Zn(II) by living and nonliving P. putida CZ1 were studied as functions of
      reaction time, initial pH of the solution and metal concentration. It was found
      that the optimum pH for Zn(II) removal by living and nonliving cells was 5.0,
      while it was 5.0 and 4.5, respectively, for Cu(II) removal. At the optimal
      conditions, metal ion biosorption was increased as the initial metal
      concentration increased. The adsorption data with respect to both metals provide
      an excellent fit to the Langmuir isotherm. The binding capacity of living cells
      is significantly higher than that of nonliving cells at tested conditions. It
      demonstrated that about 40-50% of the metals were actively taken up by P. putida
      CZ1, with the remainder being passively bound to the bacterium. Moreover,
      desorption efficiency of Cu(II) and Zn(II) by living cells was 72.5 and 45.6%
      under 0.1M HCl and it was 95.3 and 83.8% by nonliving cells, respectively. It may
      be due to Cu(II) and Zn(II) uptake by the living cells enhanced by intracellular
      accumulation.

PMID- 16289731
TI  - Surface modification of poly(ethylene terephthalate) via hydrolysis and layer-by
      layer assembly of chitosan and chondroitin sulfate to construct cytocompatible
      layer for human endothelial cells.
AB  - Surface modification of poly(ethylene terephthalate) (PET) film was performed by
      surface hydrolysis and layer-by-layer (LBL) assembly followed a mechanism of
      electrostatic adsorption of oppositely charged polymers, exemplified with
      chitosan and chondroitin sulfate (CS). Hydrolysis of PET in concentrated alkaline
      solution produced a carboxyl-enriched surface. The changes of weight loss and
      surface chemistry, morphology and wettability were monitored and verified by UV
      vis spectroscopy, atomic force microscopy (AFM) and water contact angle. Assembly
      of positively charged chitosan and negatively charged CS was then conducted in a
      LBL manner to create multilayers on the hydrolyzed PET film. The process of layer
      growth and oscillation of surface wettability were monitored by UV-vis
      spectroscopy and water contact angle measurement, respectively. In vitro cell
      culture revealed that the adherence of endothelial cells was significantly
      enhanced on the biomacromolecules-modified PET film with preserved endothelial
      cell function, in particular on those assembled with larger number of chitosan/CS
      layers. However, with regard to cell proliferation and viability properties after
      cultured for 4 days, minor difference was determined between the modified and the
      unmodified PET films.

PMID- 16289733
TI  - Lipid peroxidation and antioxidant enzymes in synovial fluid of patients with
      primary and secondary osteoarthritis of the knee joint.
AB  - OBJECTIVE: Osteoarthritis of the knee (KOA) is a common, age-related, joint
      disorder associated with loss of articular cartilage, osteophyte formation, sub
      chodral bone change and synovitis. Recent studies have shown that reactive oxygen
      species (ROS) may participate in the initiation and progression of KOA. This
      study examines potential changes in the activities of antioxidant enzymes
      (superoxide dismutase, both isoenzymes zinc-copper superoxide dismutase and
      manganese superoxide dismutase) and glutathione transformation enzymes
      (glutathione peroxidase, glutathione reductase and glutathione-S-transferase) in
      synovial fluid of KOA patients, and estimates their relationship to the degree of
      lipid peroxidation in synovial fluid evaluated by malondialdehyde concentration,
      synovial fluid viscosity, type and duration of KOA. DESIGN: Synovial fluid
      samples obtained by transdermal arthrocentesis from 41 patients with KOA (23 had
      primary KOA and 18 had secondary KOA) and 22 control subjects were analyzed.
      Activities of antioxidant enzymes were analysed with the use of kinetic method,
      MDA concentration was measured fluorometrically by the Ohkawa method, and
      synovial fluid viscosity was measured using a cone-late viscometer Brookfield DV
      II+ and a test by Ropes. RESULTS: Patients with KOA had significantly increased
      activities of all enzymes when compared to the control subjects for both KOA
      subgroups. The synovial fluid viscosity was significantly decreased and the
      synovial fluid test by Ropes was abnormal in KOA patients, mainly in the
      secondary KOA subgroup. The activities of all antioxidant enzymes were
      significantly negatively correlated with synovial fluid viscosity and duration of
      KOA. CONCLUSIONS: Patients with KOA display abnormal antioxidant status of
      synovial fluid with increased activities of antioxidant enzymes and decreased
      synovial fluid viscosity. Furthermore, synovial fluid viscosity, and activity of
      GR can be used to distinguish the primary from the secondary type of KOA.

PMID- 16289734
TI  - Stance-phase aggregate contact stress and contact stress gradient changes
      resulting from articular surface stepoffs in human cadaveric ankles.
AB  - OBJECTIVE: Determine how stepoff incongruities of the distal tibia affect
      aggregate (whole-cycle) contact stresses and contact stress gradients for a
      complete motion cycle in human cadaveric ankles. METHOD: Ten human cadaveric
      ankles were subjected to quasiphysiologic forces during stance-phase range of
      motion. Each specimen was loaded intact, with anatomic reduction of the
      anterolateral quarter of the distal tibia, and with increasing stepoffs of the
      anterolateral fragment up to 4.0mm. Transient contact stresses were measured
      using a custom-built, real-time stress transducer that sampled stresses at 132Hz
      at 1472 separate foci (sensels). Aggregate stresses were calculated by summing
      the sequential transient stress values multiplied by the transient sampling
      duration for the complete motion cycle at each sensel. Transient contact stress
      gradients were calculated at each sensel using a central-differencing formula
      applied to adjacent transient stress measurements. Aggregate contact stress
      gradients were calculated by vector summation of sequential transient stress
      gradients multiplied by the sampling duration. RESULTS: Compared to the intact
      configuration, anatomic reduction of the fragment caused minimal changes in
      aggregate contact stresses and stress gradients (30% increase compared to intact
      values). In contrast, stepoffs caused substantial increases (200% increase
      compared to intact values) in peak and mean whole-cycle stresses and gradients.
      CONCLUSIONS: Aggregate contact stresses and stress gradients quantify loading
      history for the complete motion cycle. Incongruity-associated changes in
      aggregate stresses and gradients are a surrogate for "accumulated" damage over a
      motion cycle in stepoff specimens. These loading abnormalities may be important
      determinants of posttraumatic arthritis.

PMID- 16289735
TI  - Internet marketing of bariatric surgery: contemporary trends in the
      medicalization of obesity.
AB  - In the context of political, economic, and scientific anxiety around the
      'epidemic' rise in obesity in the US, the social and historical forces
      engendering the medicalization of obesity have been widely discussed. However,
      the recent growth of bariatric-weight loss-surgery and the expanding presence of
      advertising for bariatric surgery on the Internet suggest the possible emergence
      of new loci and languages of medicalization. We sought to identify the nature and
      extent to which web advertising of bariatric surgery contributes to the
      medicalization of obesity by examining the design and textual content of 100
      bariatric surgery center websites. We found that websites, through strategic use
      of text and images, consistently describe obesity as a serious disease that
      requires professional ascertainment and supervision, entails substantial
      individual suffering, and is remedied through the transformative yet low risk
      effects of bariatric surgery. In the process, social normalcy and risk reduction
      come to replace physical criteria as the basis for determining health. Further,
      websites draw upon contradictory discourses of medicalization; that is, they
      insist upon 'external' (e.g. genetics, environment) causes of obesity to
      legitimize surgical intervention while implicating individual behaviors in
      surgical failure. From this, we suggest that the economic and professional
      motivations underlying website advertisements for bariatric surgery may result in
      confusing messages being sent to prospective patients as well as the perpetuation
      of gendered notions of obesity and the entrenchment of health disparities.

PMID- 16289736
TI  - Conversational silence, coercion, equality: the role of language in influencing
      who gets identified as abused.
AB  - Various methods of ascertaining self-reported exposure to intimate partner
      violence (IPV) in health care and research settings have been evaluated to
      identify women who interpret themselves as abused for clinical and research
      intervention. However, few interpretive frameworks have been proposed to explain
      factors that may influence the success of this ascertainment process, including
      the contribution of language in facilitating women's interpretations of
      situations as abusive across social, cultural and historical contexts. This
      omission is substantial, given that IPV is context-specific, involving
      interaction between individuals of diverse linguistic and cultural backgrounds
      and their sociocultural environment. In the first part of this paper, we outline
      hermeneutics, one interpretive theoretical tradition to describe approaches to
      interpreting IPV. Hermeneutics is a linguistic philosophy that focuses on
      questions of how people understand spoken language, written text, and themselves
      through language across sociocultural environments. Hermeneutics acknowledges
      conditions and situations that facilitate opportunities for broad shared
      understanding and vocabularies about violence between communities, professionals
      and abused women, which in turn may reduce harm to women and negotiate action
      women may want to take in response to situations they interpret as abusive. In
      the second and third parts of the paper, we compare and contrast the strengths
      and limitations of three common approaches for asking women about IPV in health
      care and research settings, and outline a multi-dimensional IPV ascertainment
      tool that incorporates the three asking approaches to facilitate professionals
      bringing broad definitions of and vocabularies about abuse to encounters with
      women. This paper provides health care researchers, clinicians and policy makers
      with a framework for understanding the potential influence of language on women's
      interpretations of IPV, including the role of community and professional
      conversational silence, coercion and equality in influencing women's
      interpretations. We look at the influence of language about intimate partner
      violence in the United States on women's interpretations of abuse, although the
      basic constructs presented here could be applied in other countries and settings.

PMID- 16289738
TI  - Does chain affiliation make a difference in efficiency of dialysis providers in
      the USA.
AB  - There has been an accelerated movement in the USA dialysis market towards
      affiliation with chain organizations. But little is known about the impact of
      this strategy of consolidation on provider performance of efficiency. This paper
      examines whether affiliation with multi-center dialysis chains creates a
      difference in technical efficiency. Data were obtained from 1994 to 2000
      Independent Renal Facility Cost Report Data files of the Centers for Medicare and
      Medicaid Studies. Using multiple time series design with a comparison group,
      technical efficiency was examined through an intertemporal data envelopment
      analysis. The results showed that mean efficiency scores of chain-affiliated
      facilities in both pre- and post-affiliation periods are slightly higher than
      those of their independent counterparts, but the difference was not statistically
      significant. Members of the first and second largest chains did not appear to
      gain benefit from affiliation. In conclusion, greater technical efficiency of
      affiliated facilities is not the result of system engagement but rather the
      result of organizational maturation, or organizational learning. Engagement with
      the two largest systems does not provide members with its theoretical premises to
      achieve technically efficient production of dialysis treatments in multiple
      product markets.

PMID- 16289737
TI  - Being around and knowing the players: networks of influence in health policy.
AB  - The accumulation and use of power is crucial to the health policy process. This
      paper examines the power of the medical profession in the health policy arena, by
      analysing which actors are perceived as influential, and how influence is
      structured in health policy. It combines an analysis of policy networks and
      social networks, to examine positional and personal influence in health policy in
      the state of Victoria, Australia. In the sub-graph of the influence network
      examined here, those most widely regarded as influential are academics, medically
      qualified and male. Positional actors (the top politician, political advisor and
      bureaucrat in health and the top nursing official) form part of a core group
      within this network structure. A second central group consists of medical
      influentials working in academia, research institutes and health-related NGOs. In
      this network locale overall, medical academics appear to combine positional and
      personal influence, and play significant intermediary roles across the network.
      While many claim that the medical profession has lost power in health policy and
      politics, this analysis yields few signs that the power of medicine to shape the
      health policy process has been greatly diminished in Victoria. Medical expertise
      is a potent embedded resource connecting actors through ties of association,
      making it difficult for actors with other resources and different knowledge to be
      considered influential. The network concepts and analytical techniques used here
      provide a novel means for uncovering different types of influence in health
      policy.

PMID- 16289739
TI  - Quality of care and its impact on population health: a cross-sectional study from
      Macedonia.
AB  - Research has revealed significant variation in both the quality of clinical care
      and the health status of populations. We conducted a study to determine if
      variations in the quality of clinical care can be quantitatively linked to
      variations in health status, at the patient and the population level. This study,
      conducted at health facilities in four municipalities in Macedonia, collected
      cross-sectional data on (1) structural measures (such as infrastructure,
      facilities, equipment and costs) and the quality of clinical care provided by
      physicians (as measured by clinical vignettes); (2) detailed health and
      socioeconomic status information on patients using the facilities; and (3) nearly
      the same information on a random sample of adults in each municipality. Data were
      collected from a total of 57 facilities, 273 physicians, 1451 patients, and 1627
      adults from the general population. The main outcome measure was health status,
      based on self-reported health surveys. Objective health measures were obtained to
      control for preexisting conditions. The main explanatory variable was quality of
      clinical care, based on physicians' clinical vignette scores. Structural measures
      were included in our model but had a more distal relationship to health status.
      We found that quality of care strongly predicted self-reported health status of
      patients using the facilities even after controlling for other factors (p < .05).
      Quality of care was also associated with higher health status for the population
      living in the surrounding community, regardless of utilization (p < .05). This
      linkage between quality of clinical care and health suggests that policies that
      improve clinical practice have the potential to improve population health more
      rapidly than other interventions.

PMID- 16289740
TI  - (Re)constructing embryos in stem cell research: exploring the meaning of embryos
      for people involved in fertility treatments.
AB  - The use of human embryos is a key controversy in public debates on stem cell
      research (SCR), yet little attention has been given to the context or sources
      from which embryos are obtained: people involved in fertility programmes. How
      they feel about the use of embryos in SCR, and what may lead them to agree or
      refuse to donate embryos, remains unexplored. In this paper, I investigate the
      views of people involved in fertility programmes who may be approached to donate
      their embryos for SCR, drawing on focus group discussions with two support groups
      in Scotland. I illustrate how people come to make particular decisions and what
      factors shape this, and show that participants' views are context-bound, borne
      out of lived experiences both within the clinic and wider society. In particular,
      the evidence highlights the importance of understanding their views of what
      constitutes a 'spare' embryo and what areas of medical research are considered
      potentially legitimate for using embryos. Peoples' understandings of embryos as
      potential lives, and the context in which embryos are created, have direct
      implications for their views about donating embryos for SCR. Attention is paid to
      how SCR further disrupts the teleology of embryos and undermines the narrative of
      life that suffuses the hopes of people undergoing fertility treatment. The paper
      also brings to the fore the sense of moral obligation experienced by participants
      who feel they have little means or power for influencing the topic and content of
      SCR. In this context, I suggest there is a need to explore further the views of
      people involved in fertility treatments in order to identify mechanisms for
      limiting the potential for coercion when SCR is embedded in and dependent on
      fertility practices. Debates about using embryos for SCR must, therefore, include
      the voices of those who thus remain marginalised.

PMID- 16289741
TI  - Men's accounts of depression: reconstructing or resisting hegemonic masculinity?
AB  - There is evidence that depressive symptoms in men are often undiagnosed and
      untreated. It has been suggested that men may find it difficult to seek help
      because culturally dominant (or hegemonic) forms of masculinity are characterised
      by emotional control and a lack of vulnerability, while depression is often
      associated with powerlessness and the uncontrolled expression of emotion.
      However, very little research exists which examines men's experiences of
      depression. We analysed 16 in-depth interviews with a wide range of men with
      depression in the UK Our analysis explored associations between depression and
      men's gender identities. We found that, as part of recovery from depression, it
      was important for men to reconstruct a valued sense of themselves and their own
      masculinity. The most common strategy was to incorporate values associated with
      hegemonic masculinity into narratives (being 'one of the boys', re-establishing
      control, and responsibility to others). While this strategy could aid recovery,
      there was also evidence that the pressures of conforming to the standards of
      hegemonic masculinity could contribute to suicidal behaviour. In contrast, a
      minority of men had found ways of being masculine which were outside hegemonic
      discourses. They emphasised their creativity, sensitivity and intelligence,
      explicitly reflected on different models of masculinity and redefined their
      'difference' as a positive feature. Our research demonstrates that it is possible
      to locate men who can, and will, talk about depression and their feelings; thus
      generalisations about depressed men always being silent are misleading. While
      some men will have the resources to construct identities that resist culturally
      dominant definitions of masculinity, many others will find it more useful (and
      perhaps less threatening) to re-interpret potentially feminising experiences as
      'masculine'. Health professionals need to be aware of the issues raised by men's
      narratives which emphasise control, strength and responsibility to others.

PMID- 16289742
TI  - The effects of economic instability on infant, neonatal, and postneonatal
      mortality rates: evidence from Taiwan.
AB  - This paper uses a panel data set comprising 23 cities for the years 1979-2002 in
      Taiwan and a fixed-effects model to find evidence of the effect of economic
      instability on infant, neonatal, and postneonatal mortality rates. In addition,
      the effects of income, demographic factors, and the availability of medical
      resources are also examined in relation to the mortalities. The most important
      finding is that infant, neonatal, and postneonatal mortality rates move counter
      cyclically with the city unemployment rate in Taiwan. The provision of national
      health insurance is also found to have a positive impact on the health of infants
      in Taiwan. Finally, the impact of economic instability on the infant, neonatal,
      and postneonatal mortality rates is found to be the strongest in the eastern part
      of Taiwan, which is the region with the fewest health care resources. The
      analysis provides evidence of the effects of economic instability on the infant,
      neonatal, and postneonatal mortality rates in a developing country, which are
      comparable to those of other countries and may provide some important insights
      into this issue.

PMID- 16289743
TI  - Vulnerability, unsafe sex and non-adherence to HAART: evidence from a large
      sample of French HIV/AIDS outpatients.
AB  - Current socio-behavioural research in HIV-infected people has tried to identify
      patients with "high-risk" profiles, i.e. who simultaneously exhibit non-adherence
      to highly active anti-retroviral therapy (HAART) and unsafe sex with
      serodiscordant partners. We challenged this approach by investigating the
      correlates of both behaviours, for homosexual men, heterosexual men and
      heterosexual women separately, among a representative sample of 4963 HIV-infected
      people in France. Variables introduced in the analysis dealt with patients'
      background and daily life, with a focus on situations of economic, social and
      personal vulnerability. Overall, 2932 patients agreed to participate, and 1809
      were both receiving HAART and sexually active. Among heterosexual women, non
      adherence and unsafe sex appeared as joint outcomes of similar situations of
      vulnerability. Among heterosexual men, these behaviours were weakly correlated
      and shared some predictors related to situations of vulnerability. Among
      homosexual men, non-adherence and unsafe sex were not correlated and had distinct
      determinants. Situations of vulnerability, the context and the motives of unsafe
      sex, as well as factors associated with non-adherence and unsafe sex varied
      greatly with gender and sexual preference. Theoretical models used for designing
      behavioural interventions should take into account this diversity.

PMID- 16289744
TI  - Dietary flavonoids: effects on xenobiotic and carcinogen metabolism.
AB  - Flavonoids are present in fruits, vegetables and beverages derived from plants
      (tea, red wine), and in many dietary supplements or herbal remedies including
      Ginkgo Biloba, Soy Isoflavones, and Milk Thistle. Flavonoids have been described
      as health-promoting, disease-preventing dietary supplements, and have activity as
      cancer preventive agents. Additionally, they are extremely safe and associated
      with low toxicity, making them excellent candidates for chemopreventive agents.
      The cancer protective effects of flavonoids have been attributed to a wide
      variety of mechanisms, including modulating enzyme activities resulting in the
      decreased carcinogenicity of xenobiotics. This review focuses on the flavonoid
      effects on cytochrome P450 (CYP) enzymes involved in the activation of
      procarcinogens and phase II enzymes, largely responsible for the detoxification
      of carcinogens. A number of naturally occurring flavonoids have been shown to
      modulate the CYP450 system, including the induction of specific CYP isozymes, and
      the activation or inhibition of these enzymes. Some flavonoids alter CYPs through
      binding to the aryl hydrocarbon receptor (AhR), a ligand-activated transcription
      factor, acting as either AhR agonists or antagonists. Inhibition of CYP enzymes,
      including CYP 1A1, 1A2, 2E1 and 3A4 by competitive or mechanism-based mechanisms
      also occurs. Flavones (chrysin, baicalein, and galangin), flavanones (naringenin)
      and isoflavones (genistein, biochanin A) inhibit the activity of aromatase
      (CYP19), thus decreasing estrogen biosynthesis and producing antiestrogenic
      effects, important in breast and prostate cancers. Activation of phase II
      detoxifying enzymes, such as UDP-glucuronyl transferase, glutathione S
      transferase, and quinone reductase by flavonoids results in the detoxification of
      carcinogens and represents one mechanism of their anticarcinogenic effects. A
      number of flavonoids including fisetin, galangin, quercetin, kaempferol, and
      genistein represent potent non-competitive inhibitors of sulfotransferase 1A1 (or
      P-PST); this may represent an important mechanism for the chemoprevention of
      sulfation-induced carcinogenesis. Importantly, the effects of flavonoids on
      enzymes are generally dependent on the concentrations of flavonoids present, and
      the different flavonoids ingested. Due to the low oral bioavailability of many
      flavonoids, the concentrations achieved in vivo following dietary administration
      tend to be low, and may not reflect the concentrations tested under in vitro
      conditions; however, this may not be true following the ingestion of herbal
      preparations when much higher plasma concentrations may be obtained. Effects will
      also vary with the tissue distribution of enzymes, and with the species used in
      testing since differences between species in enzyme activities also can be
      substantial. Additionally, in humans, marked interindividual variability in drug
      metabolizing enzymes occurs as a result of genetic and environmental factors.
      This variability in xenobiotic metabolizing enzymes and the effect of flavonoid
      ingestion on enzyme expression and activity can contribute to the varying
      susceptibility different individuals have to diseases such as cancer. As well,
      flavonoids may also interact with chemotherapeutic drugs used in cancer treatment
      through the induction or inhibition of their metabolism.

PMID- 16289746
TI  - Analysis of changes in CD20, CD55, and CD59 expression on established rituximab
      resistant B-lymphoma cell lines.
AB  - Rituximab has markedly improved treatment results for B-cell lymphoma, but there
      are resistance problems similar to those of other chemotherapy drugs. With regard
      to the acquisition of rituximab resistance, there have been several reports
      describing the relation between rituximab and complement regulatory factors or
      CD20, but many points remain unclear. To further investigate acquisition of
      resistance to rituximab-related complement-dependent cytotoxicity (CDC), we
      established rituximab-resistant B-lymphoma cell lines (RAMOS) in vitro and then
      analyzed expression of CD20, CD55, and CD59 on these resistant cells by flow
      cytometry. With repeated exposure to a low concentration of rituximab and
      complement, RAMOS cells gradually acquired rituximab resistance, and selection
      and increase of CD55(bright) and CD59(bright) cell populations due to rituximab
      related CDC were observed. With repeated exposure to a high concentration of
      rituximab and complement, RAMOS cells promptly acquired rituximab resistance, and
      CD20 expression of RAMOS cells was decreased. Not only selection of CD20(dim)
      cells but also down-modulation of CD20 caused by rituximab-related CDC appeared
      to cause the decrease in CD20 expression. We believe our findings will prove to
      be useful for prevention of or release from rituximab resistance in cases of B
      cell lymphoma.

PMID- 16289745
TI  - Par-4: a common facilitator/enhancer of extrinsic and intrinsic pathways of
      apoptosis.
AB  - Par-4 overexpression has been shown by Boehrer et al. to augment the apoptotic
      death of Jurkat T cells induced by TNF related Apoptosis Inducing Ligand (TRAIL).
      Previously, the same authors have demonstrated a parallel augmentation of
      chemotherapeutic drug-induced apoptosis in the same cell line overexpressing Par
      4. Through these and other studies, Par-4 appears to emerge as a general
      intracellular facilitator of both extrinsic and intrinsic pathways of apoptosis.
      The ability of Par-4 to modulate relevant inhibitors of apoptosis and to
      facilitate activation of alternative initiator or executioner caspases in
      contingent situations may support its role as a common facilitator/enhancer of
      apoptotic cell death. Further understanding of Par-4 biology will have
      significant clinical implications especially in overcoming drug resistance
      phenomenon in cancer.

PMID- 16289747
TI  - Molecular interactions in imatinib-DPPC liposomes.
AB  - Imatinib (Gleevec) is a novel chemotherapeutic agent against Bcr-Abl protein
      tyrozine kinase, playing a crucial role in the therapy of chronic myeloid
      leukemia (CML) and gastrointestinal stromal tumors (GIST). Our study aimed at
      designing a liposomal imatinib formulation and investigating molecular
      interactions between lipid and imatinib, within the liposomal membrane.
      Multilamellar (MLV) and small unilamellar (SUV) vesicles were prepared from alpha
      L-dipalmitoyl-phosphatidylcholine (DPPC). The effect of imatinib on the DPPC
      membrane was studied by electron paramagnetic resonance (EPR) spectroscopy and
      differential scanning calorimetry (DSC), at pH 5.2 and 9.0, where imatinib is in
      monocationic and neutral form, respectively. Our results indicate that imatinib
      interacts mainly with the DPPC head groups, leading to a slight increase in the
      mobility of the polar headgroups in case of MLVs. Contrary to that, imatinib
      causes a significant decrease in the fluidity of SUVs, which can be the result of
      a pH-dependent fusion/fission effect. The size distribution and morphology of
      liposomes were checked by dynamic light scattering and freeze-fracture electron
      microscopy. Our results direct attention to investigate the interactions of
      imatinib with artificial/biological membranes.

PMID- 16289748
TI  - A 12,000-rad porcine radiation hybrid (IMNpRH2) panel refines the conserved
      synteny between SSC12 and HSA17.
AB  - Reverse or bidirectional Zoo-FISH suggests that synteny between porcine
      chromosome 12 (SSC12) and human chromosome 17 (HSA17) is completely conserved.
      The construction of a high-resolution radiation hybrid (RH) map for SSC12
      provides a unique opportunity to determine whether chromosomal synteny is
      reflected at the molecular level by comparative gene mapping of SSC12 and HSA17.
      We report an initial, high-resolution RH map of SSC12 on the 12,000-rad IMNpRH2
      panel using CarthaGene software. This map contains a total of 320 markers,
      including 20 microsatellites and 300 ESTs/genes, covering approximately 4836.9
      cR12,000. The markers were ordered in 16 linkage groups at LOD 6.0 using
      framework markers previously mapped on the IMpRH7000-rad SSC12 and porcine
      genetic maps. Ten linkage groups ordered more than 10 markers, with the largest
      containing 101 STSs. The resolution of the current RH map is approximately 15.3
      kb/cR on SSC12, a significant improvement over the second-generation EST SSC12
      RH7000-rad map of 103 ESTs and 15 framework markers covering approximately 2287.2
      cR7000. Compared to HSA17, six distinct segments were identified, revealing macro
      rearrangements within the apparently complete synteny between SSC12 and HSA17.
      Further analysis of the order of 245 genes (ESTs) on HSA17 and SSC12 also
      revealed several micro-rearrangements within a synteny segment. A high-resolution
      SSC12 RH12,000-rad map will be useful in fine-mapping QTL and as a scaffold for
      sequencing this chromosome.

PMID- 16289749
TI  - Iron metabolism mutant hbd mice have a deletion in Sec15l1, which has homology to
      a yeast gene for vesicle docking.
AB  - Defects in iron absorption and utilization lead to iron deficiency and anemia.
      While iron transport by transferrin receptor-mediated endocytosis is well
      understood, it is not completely clear how iron is transported from the endosome
      to the mitochondria where heme is synthesized. We undertook a positional cloning
      project to identify the causative mutation for the hemoglobin-deficit (hbd) mouse
      mutant, which suffers from a microcytic, hypochromic anemia apparently due to
      defective iron transport in the endocytosis cycle. As shown by previous studies,
      reticulocyte iron accumulation in homozygous hbd/hbd mice is deficient despite
      normal binding of transferrin to its receptor and normal transferrin uptake in
      the cell. We have identified a strong candidate gene for hbd, Sec15l1, a
      homologue to yeast SEC15, which encodes a key protein in vesicle docking. The hbd
      mice have an exon deletion in Sec15l1, which is the first known mutation of a SEC
      gene homologue in mammals.

PMID- 16289751
TI  - Effect of pro-inflammatory cytokines on the toxicity of the arylhydroxylamine
      metabolites of sulphamethoxazole and dapsone in normal human keratinocytes.
AB  - Sulphonamides, such as sulphamethoxazole (SMX) and the related sulphone dapsone
      (DDS), show a higher incidence of cutaneous drug reactions (CDRs) in patients
      with the acquired immunodeficiency syndrome (AIDS) compared with human
      immunodeficiency virus (HIV) negative patients. During HIV infection, pro
      inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis
      factor-alpha (TNF-alpha) are increased. We hypothesized that this increase in pro
      inflammatory cytokines may increase the toxicity of the arylhydroxylamine
      metabolites of SMX (S-NOH) and DDS (D-NOH) in keratinocytes through a reduction
      in glutathione (GSH) content. We evaluated the effect of TNF-alpha on GSH levels
      in normal human epidermal keratinocytes (NHEK) and found a significant decrease
      in GSH after 24h. Pre-treatment with TNF-alpha also resulted in an increase in
      the recovery of D-NOH, but failed to alter drug-protein covalent adduct formation
      in NHEK. We also evaluated the effect of TNF-alpha, IL-1 beta, interferon-gamma
      (IFN-gamma), lipopolysaccharide (LPS) and conditioned media (obtained from
      monocytes stimulated with LPS) on the cytotoxicity of pre-formed
      arylhydroxylamine metabolites in NHEK. Priming cells with cytokines did not
      significantly alter the cytotoxicity of the metabolites. The effect of pre
      treatment with TNF-alpha on reactive oxygen species (ROS) generation in NHEK was
      also determined. While ROS formation in NHEK was increased in the presence of D
      NOH, TNF-alpha did not alter the level of ROS generation. Our data suggest that
      the level of GSH reduction induced by pro-inflammatory cytokines does not
      predispose NHEK to cellular toxicity from either S-NOH or D-NOH.

PMID- 16289750
TI  - Significant life events and the shape of memories to come: a hypothesis.
AB  - Much has been said about how significant life events modulate our response to
      stimuli that are integral to those events. However, we know less about the more
      general consequences of these events, that is, how they affect subsequent
      learning abilities that are seemingly irrelevant to the initial event. Here, it
      is proposed that significant life events, most often stressful in nature, alter
      future learned responses by inducing nonspecific and persistent changes in
      neuroanatomical structures. These changes are induced in the presence of sex and
      stress hormones, which are released either in response to the event itself or as
      a consequence of stages of life. To illustrate, the effects of acute stressful
      experience on learning processes and their regulation by the release of hormones
      are reviewed. I discuss how these events and their hormonal consequences alter
      anatomical substrates such as those involved in neurogenesis and synaptogenesis.
      It is proposed that these modulatory processes allow past experiences to change
      the shape of memories to come. In this way, memorable life events become less
      about the past and more about the future.

PMID- 16289752
TI  - Aluminum, restraint stress and aging: behavioral effects in rats after 1 and 2
      years of aluminum exposure.
AB  - Both aluminum (Al) and aging have been associated with neurobehavioral changes in
      mammals. In this study, the long-lasting neurobehavioral effects of prenatal
      restraint stress and oral Al exposure from conception to sacrifice were assessed
      in adult (1 year) and old (2 years) rats. Pregnant females were orally exposed to
      0, 50, and 100 mg Al/kg/day. Each Al-exposed group was divided into two
      subgroups. One of this was subjected to restraint stress (2h/day on gestation
      days 6-20). The offspring of the treated females were maintained with the same Al
      treatment until sacrifice at 1 or 2 years of age. Activity in an open-field and
      learning in a water maze were evaluated. Although no significant differences were
      observed in motor activity, a biphasic effect of Al on learning could be
      observed. Thus, exposure to 100 mg Al/kg decreased performance of the task in
      both adult and old rats when compared to animals exposed to 50 mg Al/kg. An age
      related effect on water maze performance, as well as an accumulation of Al in
      brain of rats exposed to 100 mg Al/kg at 2 years of age was found. Interestingly,
      while prenatal restraint stress did not modify behavioral parameters, Al
      accumulation was prevented by prenatal restraint.

PMID- 16289753
TI  - U.S. psychiatrists' beliefs and wants about involuntary civil commitment grounds.
AB  - This article presents results of a national U.S. survey of psychiatrists' views
      about legal grounds for involuntary civil commitment. Data from 739 Respondents
      revealed strong support for "danger to self," "danger to others," and "grave
      disability" as grounds, but weak support for "illness relapse." Psychiatrists did
      not support commitment for addiction to drugs or alcohol nor for sexual
      predators. Logit regression revealed few significant associations between
      Respondents' choice of grounds and other variables, such as race, employment
      setting, experience with commitment, and political climate of the state.
      Respondents' support for the various commitment grounds was found to be most
      significantly associated with what Respondents believed the law to be in their
      state; Respondents tended to support the grounds they believed to be the law. The
      reasons for the strong association between Respondents' beliefs and wants
      concerning commitment grounds is explored. It is suggested that Respondents have
      adopted their states' commitment grounds as their preferences through a process
      of internalization of norms. Implications of this hypothesis are discussed.

PMID- 16289754
TI  - The relationship between attachment styles and Cluster B personality disorders in
      prisoners and forensic inpatients.
AB  - The relationship between attachment styles and Cluster B personality disorders
      were examined among prisoners, forensic inpatients and controls from the general
      population. Forensic inpatients and prisoners reported significantly less
      frequently the secure attachment style (Relationship Questionnaire) and
      significantly more the fearful attachment style compared to the normal controls.
      Both forensic groups could not be distinguished from each other. Further,
      prisoners, forensic inpatients and controls could not be differentiated on the
      basis of the dismissing nor the preoccupied attachment style. With respect to
      personality pathology, almost all relationships between Cluster C pathology, on
      the one hand, and attachment styles, on the other, were significant. Cluster A
      pathology was clearly related to the secure and fearful attachment style. With
      respect to cluster B pathology, the results were more specific but also less
      clear. The results were strongly dependent on the way the personality pathology
      variables were treated, as either categorical or dimensional. None of the cluster
      B personality pathology variables were associated with the fearful attachment
      style and histrionic personality pathology was negatively associated with the
      dismissing attachment style. Antisocial personality features were associated with
      a dismissing attachment style. Borderline personality pathology, when treated as
      a categorical variable, was significantly related to the preoccupied attachment
      style. These results show that (1) cluster A and cluster C pathology are more
      strongly associated with attachment than cluster B, (2) treating personality data
      as either dimensional or categorical is of major importance to the conclusions
      that can be drawn, (3) it is important to control for the influence of co-morbid
      personality pathology when examining the relationship between (Cluster B)
      personality pathology and attachment.

PMID- 16289755
TI  - Exploring spike transfer through the thalamus using hybrid artificial-biological
      neuronal networks.
AB  - We use dynamic clamp to construct "hybrid" thalamic circuits by connecting a
      biological neuron in situ to silicon- or software-generated "neurons" through
      artificial synapses. The purpose is to explore cellular sensory gating mechanisms
      that regulate the transfer efficiency of signals during different sleep-wake
      states. Hybrid technology is applied in vitro to different paradigms such as: (1)
      simulating interactions between biological thalamocortical neurons, artificial
      reticular thalamic inhibitory interneurons and a simulated sensory input, (2)
      grafting an artificial sensory input to a wholly biological thalamic network that
      generates spontaneous sleep-like oscillations, (3) injecting in thalamocortical
      neurons a background synaptic bombardment mimicking the activity of
      corticothalamic inputs. We show that the graded control of the strength of
      intrathalamic inhibition, combined with the membrane polarization and the
      fluctuating synaptic noise in thalamocortical neurons, is able to govern
      functional shifts between different input/output transmission states of the
      thalamic gate.

PMID- 16289756
TI  - Sensitivity and resolution in proton solid-state NMR at intermediate deuteration
      levels: quantitative linewidth characterization and applications to correlation
      spectroscopy.
AB  - We present a systematic study of proton linewidths in rigid solids as a function
      of sample spinning frequency and proton density, with the latter controlled by
      the ratio of protonated and perdeuterated model compounds. We find that the
      linewidth correlates more closely with the overall proton density (rho(H)) than
      the size of local clusters of (1)H spins. At relatively high magic-angle spinning
      (MAS) rates, the linewidth depends linearly upon the inverse MAS rate. In the
      limit of infinite spinning rate and/or zero proton concentration, the linewidth
      extrapolates to a non-zero value, owing to contributions from scalar couplings,
      chemical shift dispersion, and B(0) field inhomogeneity. The slope of this line
      depends on the overall concentration of unexchangeable protons in the sample and
      the spinning rate. At up to 30% protonation levels ( approximately 2
      (1)H/100A(3)), proton detection experiments are demonstrated to have a
      substantial (2- to 3-fold) sensitivity gain over corresponding (13)C-detected
      experiments. Within this range, the absolute sensitivity increases with
      protonation level; the optimal compromise between sensitivity and resolution is
      in the range of 20-30% protonation. We illustrate the use of dilute protons for
      polarization transfer to and from low-gamma spins within 5A, and to be utilized
      as both magnetization source and detection spins. The intermediate protonation
      regime enhances relaxation properties, which we expect will enable new types of
      (1)H correlation pulse sequences to be implemented with improved resolution and
      sensitivity.

PMID- 16289757
TI  - NMR determination of photorespiration in intact leaves using in vivo 13CO2
      labeling.
AB  - Solid-state 13C NMR measurements of intact soybean leaves labeled by 13CO2 lead
      to the conclusion that photorespiration is 17% of photosynthesis for a well
      watered and fertilized plant. This is the first direct assessment of the level of
      photorespiration in a functioning plant. A 13C{31P} rotational-echo double
      resonance (REDOR) measurement tracked the incorporation of 13C label into
      intermediates in the Calvin cycle as a function of time. For labeling times of 5
      min or less, the isotopic enrichment of the Calvin cycle depends on the flux of
      labeled carbon from 13CO2, relative to the flux of unlabeled carbon from
      glycerate returned from the photorespiratory cycle. Comparisons of these two
      rates for a fixed value of the 13CO2 concentration indicate that the ratio of the
      rate of photosynthesis to the rate of photorespiration of ribulose-1,5
      bisphosphate carboxylase/oxygenase (Rubisco) in soybean leaves is 5.7. This
      translates into a photorespiratory CO2 loss that is 21% of net CO2 assimilation,
      about 80% of the value estimated from Rubisco kinetics parameters. The ratio of
      rates is reduced at low external CO2 concentrations, as measured by net carbon
      assimilation rates. The carbon assimilation was determined from 13C-label spin
      counts converted into total carbon by the REDOR-determined isotopic enrichments
      of the Calvin cycle. The net carbon assimilation rates indicate that the rate of
      decarboxylation of glycine is not directly proportional to the oxygenase activity
      of Rubisco as is commonly assumed.

PMID- 16289758
TI  - Role of early stress in the individual differences in host response to viral
      infection.
AB  - Early negative life events, especially during the neonatal period, resulted in
      long lasting, irreversible effects on well being. The goal of the following study
      was to examine the lifelong effects of neonatal stress on the response to an
      influenza viral infection. Mouse pups were repeatedly separated from their dams
      between postnatal days 1-14 (maternal separation, MSP). As adults, these mice
      were infected with influenza A/PR8 virus and lung cytokine and plasma
      corticosterone responses to the viral infection were measured. The results
      indicated that MSP augmented several aspects of the response to infection. First,
      infection-induced lung proinflammatory cytokine (interleukin (IL)-1, IL-6, and
      tumor necrosis factor (TNF)-alpha) mRNA expression was higher in MSP mice
      compared to controls. In addition, MSP augmented infection-induced lung IL-12 and
      interferon (IFN)-gamma, but had no effect on IL-18 mRNA. Interestingly, MSP
      induced increase in IL-1, TNF-alpha and IFN-gamma mRNA expression was evident in
      females, but not in males. These findings suggest that MSP disrupted the
      regulation of innate resistance resulting in enhanced cytokine responses in the
      lungs during an infectious challenge. These changes in host response to the viral
      infection were accompanied by an increase in viral replication in lungs of MSP
      mice. Interestingly, influenza-induced corticosterone secretion was blunted in
      MSP mice, suggesting that the increase in immune reactivity to the virus was due
      to lack of glucocorticoid feedback control. These data demonstrate that neonatal
      stress has implications for host resistance to infection throughout life. Thus,
      long lasting effects of negative life events on health and disease may be the
      basis for the individual differences in host susceptibility to infection.

PMID- 16289759
TI  - Using sediment quality guidelines for dredged material management in commercial
      ports from Spain.
AB  - Dredged material contamination was assessed in different commercial ports from
      Spain: Port of Cadiz and Huelva, South West; Bilbao and Pasajes, North; Cartagena
      and Barcelona, East; Coruna, North West. Sediment from different locations of
      these ports was sampled and was characterized following the Spanish
      recommendations for dredged material management. This characterization included
      grain size distribution, organic matter content and concentration of the chemical
      compounds included in the list of pollutants and hazardous substances (As, Cd,
      Cu, Cr, Hg, Ni, Pb and Zn; PCB congeners IUPAC number 28, 52, 101, 118, 138, 153
      and 180; PAHs were also analyzed). The results were compared to the limit values
      of Spanish Action Levels that define the different categories for assessment and
      management. A set of empirically derived sediment quality guidelines (SQG) was
      used to assess the possible toxicity of the dredged materials and to improve the
      use of the chemical approach to characterize dredged material for its management.

PMID- 16289760
TI  - Nonlinear multivariate analysis of neurophysiological signals.
AB  - Multivariate time series analysis is extensively used in neurophysiology with the
      aim of studying the relationship between simultaneously recorded signals.
      Recently, advances on information theory and nonlinear dynamical systems theory
      have allowed the study of various types of synchronization from time series. In
      this work, we first describe the multivariate linear methods most commonly used
      in neurophysiology and show that they can be extended to assess the existence of
      nonlinear interdependence between signals. We then review the concepts of entropy
      and mutual information followed by a detailed description of nonlinear methods
      based on the concepts of phase synchronization, generalized synchronization and
      event synchronization. In all cases, we show how to apply these methods to study
      different kinds of neurophysiological data. Finally, we illustrate the use of
      multivariate surrogate data test for the assessment of the strength (strong or
      weak) and the type (linear or nonlinear) of interdependence between
      neurophysiological signals.

PMID- 16289761
TI  - New treatment regimes for virus-induced exacerbations of asthma.
AB  - This review will focus on the role of viruses as causes of asthma exacerbations.
      The article will briefly review the current literature supporting this view, with
      a special focus on human rhinovirus (RV), the main virus associated with
      exacerbations of asthma. The review will then refer to possible strategies for
      treatment, and will include discussion on treatment with specific anti-viral
      therapy and type I interferon as a treatment for RV. The review will also include
      a discussion on current therapies for asthma, such as glucocorticosteroid and
      beta(2) agonist therapy alone and in combination and why this may be relevant to
      virus-induced exacerbations of asthma. Finally, the potential for future anti
      inflammatory/immunomodulatory therapies with a focus on NF-kappaB inhibition will
      be discussed.

PMID- 16289762
TI  - A review of guidelines for antibacterial use in acute exacerbations of chronic
      bronchitis.
AB  - Acute exacerbations of chronic bronchitis (AECB) affect a significant proportion
      of the adult population worldwide and are associated with a substantial
      socioeconomic burden. The majority of episodes of AECB are bacterial in aetiology
      and patients are generally treated empirically with orally administered
      antibacterial agents. Guidelines for the management of AECB have been developed
      by a number of national health authorities and international organisations, with
      the aim of promoting rational selection of antibacterial therapy to minimise the
      risk of treatment failure and subsequent hospitalisation while containing the
      development and spread of antibacterial resistance. This paper reviews a number
      of recently published or updated AECB treatment guidelines, focusing on patient
      stratification strategies, antibacterial treatment recommendations, and newer
      antibacterial treatment options, including respiratory fluoroquinolones and the
      ketolide telithromycin, which have recently been added to a number of national
      treatment guidelines.

PMID- 16289763
TI  - Back extensor muscle oxygenation and fatigability in healthy subjects and low
      back pain patients during dynamic back extension exertion.
AB  - The purpose of this study was to assess if chronic low back pain patients have
      impaired paraspinal muscle O2 turnover and endurance capacity as compared to
      healthy control subjects during dynamic exercise. Middle-aged healthy male
      subjects (n = 12, control) and male patients with chronic low back pain (n = 17,
      CLBP) participated in the study. L4-L5 level paraspinal muscle fatigue was
      objectively assessed during earlier validated 90 s dynamic back endurance test
      (spectral EMG, MPFslope). Also EMG amplitude (EMGamplitude) and initial MPF
      (MPFinitial) were assessed from the initial 5 s of the endurance contraction.
      Simultaneously near infrared spectroscopy (NIRS) was used for quantitative
      measurement of local L4-L5 paraspinal muscle O2 consumption. Subcutaneous tissue
      thickness (ATT) was measured from the EMG and NIRS recording sites. The results
      indicated that control and CLBP groups were compatible as regarding
      anthropometric variables, paraspinal muscle activation levels (EMGamplitude),
      initial MPF (MPFinitial) and ATT. When the ATT was used as a covariate in the
      ANOVA analysis, CLBP group did not show significantly greater paraspinal muscle
      fatigability (right MPFslope - 12.2 +/- 10.7%/min, left right MPFslope - 12.6 +/-
      13.3%/min) or O2 consumption (right NIRSslope - 52.8 +/- 79.6 MUM/l/s) as
      compared to healthy controls (right MPFslope - 11.9 +/- 7.6%/min, left MPFslope -
      12.7 +/- 8.6%/min, right NIRSslope - 53.7 +/- 95.2 MUM/l/s). As a conclusion,
      these CLBP male patients did not show any impaired rate of paraspinal muscle
      oxygen consumption or excessive paraspinal muscle fatigability during dynamic
      exercise as compared with healthy controls. Subcutaneous tissue thickness has a
      strong influence on the NIRS and EMG amplitude measurements and, if unchecked, it
      could result in the false interpretation of the results.

PMID- 16289764
TI  - Lipoteichoic acid-induced nitric oxide synthase expression in RAW 264.7
      macrophages is mediated by cyclooxygenase-2, prostaglandin E2, protein kinase A,
      p38 MAPK, and nuclear factor-kappaB pathways.
AB  - We recently reported that lipoteichoic acid (LTA), a cell wall component of the
      gram-positive bacterium Staphylococcus aureus, stimulated inducible nitric oxide
      synthase (iNOS) expression, nitric oxide (NO) release, and cyclooxygenase-2 (COX
      2) expression in RAW 264.7 macrophages. This study was carried out to further
      investigate the roles of COX-2 and prostaglandin E2 (PGE2) in LTA-induced iNOS
      expression and NO release in RAW 264.7 macrophages. Treatment of RAW 264.7
      macrophages with LTA caused a time-dependent increase in PGE2 release. LTA
      induced iNOS expression and NO release were inhibited by a non-selective COX
      inhibitor (indomethacin), a selective COX-2 inhibitor (NS-398), an adenylyl
      cyclase (AC) inhibitor (dideoxyadenosine, DDA), and a protein kinase A (PKA)
      inhibitor (KT-5720). Furthermore, both PGE2 and the direct PKA activator,
      dibutyryl-cAMP, also induced iNOS expression in a concentration-dependent manner.
      Stimulation of RAW 264.7 macrophages with LTA, PGE2, and dibutyryl-cAMP all
      caused p38 MAPK activation in a time-dependent manner. LTA-mediated p38 MAPK
      activation was inhibited by indomethacin, NS-398, and SB 203580, but not by PD
      98059. The PGE2-mediated p38 MAPK activation was inhibited by DDA, KT-5720, and
      SB 203580, but not by PD 98059. LTA caused time-dependent activation of the
      nuclear factor-kappaB (NF-kappaB)-specific DNA-protein complex formation. The LTA
      induced increase in kappaB-luciferase activity was inhibited by indomethacin, NS
      398, KT-5720, and a dominant negative mutant of p38 alphaMAPK (p38 alphaMAPK DN).
      These results suggest that LTA-induced iNOS expression and NO release involve COX
      2-generated PGE2 production, and AC, PKA, p38 MAPK, and NF-kappaB activation in
      RAW 264.7 macrophages.

PMID- 16289765
TI  - Jaagsiekte sheep retrovirus-specific immune responses induced by vaccination: a
      comparison of immunisation strategies.
AB  - Jaagsiekte sheep retrovirus (JSRV) is the aetiological agent of ovine pulmonary
      adenocarcinoma (OPA). No JSRV-specific immunological responses have been detected
      in clinical cases of OPA or in experimentally infected lambs. The aim of the
      present study was to induce immune responses in sheep against JSRV proteins using
      several immunisation strategies. The vaccines were administered subcutaneously
      and intradermally, or intranasally, in adjuvant. Antibodies were measured by
      ELISA and immunoblotting, and T cell responses by lymphoproliferation assay.
      Antibodies specific for JSRV-capsid protein were induced by inoculation of
      recombinant proteins in adjuvant, and transient JSRV-specific T cell responses by
      intranasal inoculation with inactivated virus. These results will help in the
      design of a protective vaccine against JSRV infection and the development of OPA.

PMID- 16289766
TI  - Intranasal immunization with serum opacity factor (SOF) of Streptococcus pyogenes
      fails to protect mice against lethal mucosal challenge with a heterologous
      strain.
AB  - Streptococcus pyogenes is a human pathogen causing invasive and non-invasive
      diseases, as well as severe sequels, such as rheumatic fever. Several bacterial
      factors have been proposed as candidate vaccine antigens. Among them, the serum
      opacity factor (SOF), which was able to confer protective immunity against an
      intraperitoneal challenge after vaccination by the parenteral route. In an
      attempt to develop more efficient vaccines, we combined SOF with an additional
      well-known protective antigen, namely, the fibronectin-binding protein I (SfbI).
      Intranasal immunization of mice with SOF and SfbI stimulates strong systemic and
      mucosal immune responses against both antigens. Animals vaccinated with SfbI,
      alone or in combination with SOF, were also efficiently protected against a
      lethal challenge with a SOF/SfbI-positive virulent S. pyogenes strain (80%
      survival). In contrast, those vaccinated with SOF alone were not protected
      against a mucosal challenge (100% lethality), which mimics more closely natural
      infections. These results highlight the importance of developing adequate
      experimental animal models to evaluate vaccine efficiency, according to the
      selected antigen.

PMID- 16289767
TI  - Influenza vaccine uptake in adults aged 50-64 years: policy and practice in
      England 2003/2004.
AB  - A small national study was carried out in England in 2003/2004 to ascertain the
      views of primary care trusts (PCTs) and general practitioners (GPs) on whether
      influenza immunisation should be extended to all people aged 50-64 years from the
      current recommendation of 65 years or more. Results showed that as many primary
      care trusts would be in favour, as would not be in favour. A similarly divided
      view was expressed by general practitioners. Vaccine uptake rates for high-risk
      (HR) and low-risk (LR) adults aged 50-64 years in the study population were
      higher in those practices where the GP was in favour of a more inclusive policy
      of offering flu vaccine to all persons aged 50 years or more, compared with those
      that did not favour this policy (60% versus 54% HR (p=0.02) and 16% versus 11% LR
      (p=0.02)). Higher rates of vaccine uptake for low-risk patients aged 50-64 years
      were also reported from practices where GPs perceived a greater health benefit of
      immunisation for this age group. Although policy for recommending vaccine to all
      patients aged 50 years or more is established elsewhere, opinion on whether such
      a policy should be adopted in England is currently divided amongst those
      providing local health services.

PMID- 16289768
TI  - Pseudomyasthenia in a patient with pontine glioma.

PMID- 16289769
TI  - A case of late-onset Segawa syndrome (autosomal dominant dopa-responsive
      dystonia) with a novel mutation of the GTP-cyclohydrase I (GCH1) gene.
AB  - We report a case of a 46-year-old Japanese woman with hereditary progressive
      dystonia with marked diurnal fluctuations and dopa-responsive dystonia (HPD/DRD).
      She developed difficulty in walking at the age of 44 years due to bradykinesia as
      well as hand tremors, muscle rigidity, increased tendon reflexes and mild
      dystonia in the lower extremities, all of which responded remarkably to low doses
      of levodopa (150 mg/day). Biopterin and neopterin concentrations in the
      cerebrospinal fluid (CSF) were decreased. Analysis of the guanosine 5'
      triphosphate cyclohydrolase I (GCH1) gene revealed a novel mutation (W53X) in one
      allele. The GCH1 activity that was expressed in mononuclear blood cells was
      almost half the normal value (usually 2-20% of the normal value (39.0+/-9.2
      pmol/ml) in patients with HPD/DRD). The relatively conserved GCH1 activity that
      is expressed in stimulated peripheral blood mononuclear cells may be related to
      the late clinical symptoms in this patient.

PMID- 16289770
TI  - Arterial acid-base status during digestion and following vascular infusion of
      NaHCO(3) and HCl in the South American rattlesnake, Crotalus durissus.
AB  - Digestion is associated with gastric secretion that leads to an alkalinisation of
      the blood, termed the "alkaline tide". Numerous studies on different reptiles and
      amphibians show that while plasma bicarbonate concentration ([HCO(3)(-)](pl))
      increases substantially during digestion, arterial pH (pHa) remains virtually
      unchanged, due to a concurrent rise in arterial PCO(2) (PaCO(2)) caused by a
      relative hypoventilation. This has led to the suggestion that postprandial
      amphibians and reptiles regulate pHa rather than PaCO(2). Here we characterize
      blood gases in the South American rattlesnake (Crotalus durissus) during
      digestion and following systemic infusions of NaHCO(3) and HCl in fasting animals
      to induce a metabolic alkalosis or acidosis in fasting animals. The magnitude of
      these acid-base disturbances were similar in magnitude to that mediated by
      digestion and exercise. Plasma [HCO(3)(-)] increased from 18.4+/-1.5 to 23.7+/
      1.0 mmol L(-1) during digestion and was accompanied by a respiratory compensation
      where PaCO(2) increased from 13.0+/-0.7 to 19.1+/-1.4 mm Hg at 24 h. As a result,
      pHa decreased slightly, but were significantly below fasting levels 36 h into
      digestion. Infusion of NaHCO(3) (7 mmol kg(-1)) resulted in a 10 mmol L(-1)
      increase in plasma [HCO(3)(-)] within 1 h and was accompanied by a rapid
      elevation of pHa (from 7.58+/-0.01 to 7.78+/-0.02). PaCO(2), however, did not
      change following HCO(3)(-) infusion, which indicates a lack of respiratory
      compensation. Following infusion of HCl (4 mmol kg(-1)), plasma pHa decreased by
      0.07 units and [HCO(3)(-)](pl) was reduced by 4.6 mmol L(-1) within the first 3
      h. PaCO(2), however, was not affected and there was no evidence for respiratory
      compensation. Our data show that digesting rattlesnakes exhibit respiratory
      compensations to the alkaline tide, whereas artificially induced metabolic acid
      base disturbances of same magnitude remain uncompensated. It seems difficult to
      envision that the central and peripheral chemoreceptors would experience
      different stimuli during these conditions. One explanation for the different
      ventilatory responses could be that digestion induces a more relaxed state with
      low responsiveness to ventilatory stimuli.

PMID- 16289771
TI  - Elevated plasma concentrations of haptoglobin in European brown bears during
      hibernation.
AB  - Haptoglobin (Hp), a hemoglobin-binding protein, is known as an acute phase
      protein and increases during the acute phase of inflammation in most mammals. We
      reported previously in brown bears that the mean Hp concentrations were higher in
      blood samples obtained in winter than those in spring. To examine a possible
      relation of the seasonal variations of Hp to hibernation, in the present study,
      we measured the plasma concentrations of Hp as well as some other acute phase
      proteins (alpha(2)-macroglobulin, alpha(1)-antitrypsin, C-reactive protein) in 6
      European brown bears (Ursus arctos), from which blood samples were obtained at 5
      6 different months of year including February, the time of hibernation. The Hp
      concentrations showed clear seasonal variations, being highest in February. The
      alpha(2)-macroglobulin concentrations also showed a similar but much smaller rise
      in February, but those of alpha(1)-antitrypsin and C-reactive protein did not
      show any seasonal variations. Our results suggest that the seasonal variation of
      plasma Hp concentration in brown bears is associated with a hibernation-specific
      mechanism more than that of acute phase response.

PMID- 16289772
TI  - [Belated decompensation of an Imerslund-Grasbeck disease].
AB  - Imerslund-Grasbeck disease is an autosomic recessive disease characterised by a
      megaloblastic anemia due to a vitamin B12 deficiency and by a moderate
      proteinuria without kidney failure. It is caused by the malabsorption of
      Cobalamin-intrinsic factor complex bringing into play cubulin and other proteins
      (megaline, amnioless), some mutations of which are described at present. We
      report herein the observation of a child whose diagnosis was made belatedly
      during an acute decompensation with biological hemophagocytic syndrome. Its
      evolution was marked by the appearance of neurological disorders at the beginning
      of the vitamin B12 substitution treatment. These disorder regressed as the dosage
      was increase. The purpose of this observation is to recapitulate the main
      characteristics of this disease and to review the current data.

PMID- 16289773
TI  - Individual differences in extraversion and dopamine genetics predict neural
      reward responses.
AB  - Psychologists have linked the personality trait extraversion both to differences
      in reward sensitivity and to dopamine functioning, but little is known about how
      these differences are reflected in the functioning of the brain's dopaminergic
      neural reward system. Here, we show that individual differences in extraversion
      and the presence of the A1 allele on the dopamine D2 receptor gene predict
      activation magnitudes in the brain's reward system during a gambling task. In two
      functional MRI experiments, participants probabilistically received rewards
      either immediately following a behavioral response (Study 1) or after a 7.5 s
      anticipation period (Study 2). Although group activation maps revealed
      anticipation- and reward-related activations in the reward system, individual
      differences in extraversion and the presence of the D2 Taq1A allele predicted a
      significant amount of inter-subject variability in the magnitudes of reward
      related, but not anticipation-related, activations. These results demonstrate a
      link between stable differences in personality, genetics, and brain functioning.

PMID- 16289774
TI  - The synthetic epoxyquinoids jesterone dimer and epoxyquinone A monomer induce
      apoptosis and inhibit REL (human c-Rel) DNA binding in an IkappaBalpha-deficient
      diffuse large B-cell lymphoma cell line.
AB  - The NF-kappaB transcription factor signaling pathway is constitutively active in
      many human cancers, and inhibition of this pathway can often kill cancer cells by
      inducing apoptosis. In this study, we show that two synthetic epoxyquinoids,
      jesterone dimer (JD) and epoxyquinone A monomer (EqM), are equally effective at
      inhibiting the growth of two human lymphoma cell lines that have constitutively
      nuclear REL (human c-Rel) DNA-binding complexes, but either express (SUDHL-4
      cells) or do not express (RC-K8 cells) the NF-kappaB inhibitor IkappaBalpha.
      Furthermore, in these cells, both JD and EqM dose-dependently induced apoptosis,
      inhibited REL DNA-binding activity, and converted REL to a high molecular weight
      form. In A293 cells, JD and EqM inhibited the DNA-binding activity of
      overexpressed REL, but not p50. Replacement of Cys-27 with Ser in REL reduced JD-
      and EqM-mediated inhibition of REL DNA-binding activity. These results suggest
      that JD and EqM can induce apoptosis in IkappaBalpha-deficient lymphoma cells
      through a mechanism involving direct inhibition of transcription factor REL.

PMID- 16289775
TI  - Bioavailability and cellular effects of metals on Lumbricus terrestris inhabiting
      volcanic soils.
AB  - Whether the radial thickness (RT) of the chloragogenous tissue and intestinal
      epithelium of earthworms (Lumbricus terrestris) reflects the bioavailability of
      metals in soils was investigated in two areas, one with active volcanism (Furnas)
      and another with no volcanic activity since 3 million years ago (Santa Maria), in
      the Azores. Metal contents in soil samples and earthworms from the two areas were
      analyzed. Autometallography and measurements of the RT were performed in the
      chloragogenous tissue and intestinal epithelium. Earthworms from the active
      volcanic area demonstrated lower RT of chloragogenous tissue and intestinal
      epithelium as well as higher levels of bioavailable metals, especially Zn and Cd.
      Comparison of bioavailable metal contents between both areas suggests a higher
      risk for uptake of potentially toxic metals in the active volcanic area than in
      the non-active volcanic area, which is reflected by the lower RT of the
      chloragogenous tissue and intestinal epithelium in the former.

PMID- 16289776
TI  - Genotoxicity biomarkers and acetylcholinesterase activity in natural populations
      of Mytilus galloprovincialis along a pollution gradient in the Gulf of Oristano
      (Sardinia, western Mediterranean).
AB  - A year-round biomonitoring study on blue mussels (Mytilus galloprovincialis) was
      carried out in 4 selected sites along the Gulf of Oristano (Sardinia, Italy): a
      commercial port (Port), the outlet of the S'Ena Arrubia and Marceddi lagoons (in
      the catchment area of intensive agricultural and diary activities, and abandoned
      mining), and a reference site (North). Heavy metal concentrations in sediments
      from Marceddi were 2-3 to 10-20 times higher in Pb, Cd and Zn, respectively, than
      those found at North and S'Ena Arrubia. Higher values (P<0.05) of micronuclei
      frequency were detected in mussels from Marceddi and Port compared to those
      detected in mussels from North and S'Ena Arrubia. DNA damage in animals from
      North was significantly lower than that at the other sites. Results of
      acetylcholinesterase inhibition consistently showed the strongest effects in
      mussels from Port and Marceddi. Our results suggest that these biomarkers can be
      used in coastal marine biomonitoring as early signals of exposure and adverse
      effects along a pollution gradient.

PMID- 16289777
TI  - Enhancement of intestinal absorption of poorly absorbed hydrophilic compounds by
      simultaneous use of mucolytic agent and non-ionic surfactant.
AB  - The effect of co-administration of a mucolytic agent with a penetration enhancer
      was assessed on the intestinal absorption of poorly absorbed hydrophilic
      compounds. Fluorescein isothiocyanate-labeled dextran with average molecular
      weight of ca. 4.4 kDa (FD-4) was used as a model compound, and N-acetylcysteine
      (NAC) was used as a mucolytic agent. Sodium caprate (C10), tartaric acid (TA),
      sodium taurodeoxycholate (TDC), sodium dodecyl sulfate (SDS), p-t-octyl phenol
      polyoxyethylene-9.5 (Triton X-100, TX-100) were selected as penetration enhancers
      with different mechanisms of action. Various dosing solutions containing a
      penetration enhancer in the absence or in the presence of NAC were directly
      administered into the exposed rat jejunum, and the bioavailability of FD-4 up to
      2 h was determined. The extent of improvement by co-administration was highly
      dependent on the penetration enhancer species applied. The observed enhancement
      was thought to result from the mucolytic activity of NAC, which can reduce the
      mucus viscosity and facilitate the penetration of FD-4 to mucosal membrane. Among
      the combinations tested, the simultaneous administration of NAC and TX-100
      provided the highest enhancement (22.5-fold) of intestinal FD-4 absorption
      compared to the control. Although the detailed mechanism for the observed drastic
      improvement is unclear, one possible reason was thought to be due to the improved
      diffusivity of TX-100 micellar system in the mucus layer. All these results
      suggest that the combination of a mucolytic agent and a non-ionic surfactant may
      have potential as an enhancing system for peroral delivery of poorly absorbed
      hydrophilic compounds like protein and peptide drugs.

PMID- 16289778
TI  - In silico aided metabolic engineering of Saccharomyces cerevisiae for improved
      bioethanol production.
AB  - In silico genome-scale cell models are promising tools for accelerating the
      design of cells with improved and desired properties. We demonstrated this by
      using a genome-scale reconstructed metabolic network of Saccharomyces cerevisiae
      to score a number of strategies for metabolic engineering of the redox metabolism
      that will lead to decreased glycerol and increased ethanol yields on glucose
      under anaerobic conditions. The best-scored strategies were predicted to
      completely eliminate formation of glycerol and increase ethanol yield with 10%.
      We successfully pursued one of the best strategies by expressing a non
      phosphorylating, NADP(+)-dependent glyceraldehyde-3-phosphate dehydrogenase in S.
      cerevisiae. The resulting strain had a 40% lower glycerol yield on glucose while
      the ethanol yield increased with 3% without affecting the maximum specific growth
      rate. Similarly, expression of GAPN in a strain harbouring xylose reductase and
      xylitol dehydrogenase led to an improvement in ethanol yield by up to 25% on
      xylose/glucose mixtures.

PMID- 16289779
TI  - Identification of distributed metabolic objectives in the hypermetabolic liver by
      flux and energy balance analysis.
AB  - A methodology for inferring distributed metabolic objectives from time series
      flux data is developed by combining metabolic flux analysis, pathway
      identification, free energy balances, and nested optimization. This methodology
      is used to investigate the metabolic response of the rat liver to burn injury
      induced whole body inflammation. Gibbs free energy changes were computed for
      stoichiometrically balanced sequences of reactions, or pathways, rather than
      individual reactions, to account for energetic coupling between reactions.
      Systematic enumeration of pathways proceeded by elementary flux mode (EFM)
      analysis. Together with stoichiometric balances and external metabolite flux
      measurements, the DeltaG(PATH)(o) criterion provided sufficient constraints to
      solve a series of nested optimization problems on the metabolic goal functions
      and associated flux distributions of fasted livers during the first-week time
      course of burn injury. The optimization results suggest that there is a
      consistent metabolic goal function for the liver that is insensitive to the
      changing metabolic burdens experienced by the liver during the first-week time
      course. As defined by the goal function coefficients, the global metabolic
      objective was to distribute the metabolic resources between amino acid metabolism
      and ketone body synthesis. These findings point to a role for the time-invariant
      structure of the metabolic reaction network, expressed as stoichiometric and
      thermodynamic constraints, in shaping the cellular metabolic objective.

PMID- 16289780
TI  - [Weight of obesity in (pre)type 2 diabetes in children and adolescents: how and
      when to screen for?].
AB  - There has been wide recognition in the past decade of the increasing frequency of
      type 2 diabetes in youth, largely but not exclusively in North America. In some
      American locations and populations, incidence and prevalence of type 2 diabetes
      are much higher than those of type 1 diabetes, because of increased calorie and
      fat intake, and decreased exercise. The increasing prevalence of type 2 diabetes
      in the United States has closely paralleled the increase in childhood obesity
      noted there, but now across the Western world. Besides obesity, the other youth
      risk factors for type 2 diabetes are: ethnicity, puberty, family history,
      metabolic syndrome, polycystic ovary syndrome, acanthosis nigricans. Any feature
      or condition associated with insulin resistance/hyperinsulinemia should alert to
      screen youth at increased risk for (pre)type 2 diabetes. Treatment goals are to
      decrease weight and increase exercise, to normalize insulinemia, glycemia and
      HbA1c, to control hypertension and hyperlipidemia. The aim of the pharmacological
      therapy is to decrease insulin resistance, namely by metformin. Sometimes,
      insulin therapy is necessary.

PMID- 16289782
TI  - [Atypic radiologic aspect of a renal cell carcinoma in children].
AB  - Renal cell carcinoma is rare in children and is usually found in late childhood.
      The authors report on an exceptional case of renal cell carcinoma in a 10-year
      old girl. The radiological aspect is misleading and has not been previously
      reported in the literature. Renal cortex was thin because of congenital megalo
      ureter, so the tumor developed entirely into excretory cavities (to the proximal
      ureter), while a primitive urothelial disease (tumoral or inflammatory) was first
      evoked. The atrophied cortex was the tumoral starting point which prolapsed into
      excretory cavities, upraising the urothelial epithelium.

PMID- 16289783
TI  - Association analysis of the glycogen synthase kinase-3beta gene in bipolar
      disorder.
AB  - Glycogen synthase kinase-3beta (GSK3beta) is a target of lithium as well as
      sodium valproate, both of which are effective mood stabilizing
      prophylatics/treatments for bipolar disorder, a highly heritable psychiatric
      disorder. Though it is not clear whether the mood stabilizing effects of these
      drugs act directly through GSK3beta, it is a good candidate for mediating at
      least part of lithium's action, and is an aetiological candidate gene for the
      disease itself. Recently, a potential locus for bipolar disorder was reported on
      chromosome 3q, close to 3q13.37 where GSK3beta maps. We conducted an association
      study to test the hypothesis that polymorphism of GSK3beta is involved in
      susceptibility to bipolar disorder by examining association between GSK3beta-gene
      polymorphisms and bipolar disorder. Of the five polymorphisms we examined, three
      were very rare in the study population and were not examined further. Neither of
      the remaining two polymorphisms we examined showed association with bipolar
      disorder. Thus, it is unlikely that the GSK3beta-gene is a risk factor for
      bipolar disorder in our sample, but we cannot exclude the gene completely as
      other unknown polymorphisms in the gene may increase susceptibility.

PMID- 16289784
TI  - Involvement of PKA, MAPK/ERK and CaMKII, but not PKC in the acute antidepressant
      like effect of memantine in mice.
AB  - This study investigated the cellular signaling pathways involved in the acute
      antidepressant-like action of memantine in the forced swimming test (FST) in
      mice. The immobility time in the FST was reduced by memantine (3-10 mg/kg, i.p.).
      The anti-immobility effect of memantine (3 mg/kg, i.p.) was prevented by
      pretreatment with H-89 (1 microg/site, i.c.v., an inhibitor of PKA), PD098059 (5
      microg/site, i.c.v., an inhibitor of MAPK/ERK), KN-62 (1 microg/site, i.c.v., an
      inhibitor of CaMKII), but not with chelerythrine (1 microg/site, i.c.v., an
      inhibitor of PKC). Taken together, these results firstly demonstrate that the
      acute antidepressant-like effect of memantine seems to be dependent on the
      cellular signaling modulated by PKA, CaMKII and MAPK/ERK, but not by PKC.

PMID- 16289785
TI  - Respiratory infections and asthma.
AB  - Respiratory tract infections caused by both viruses and/or atypical bacteria are
      involved in the pathogenesis of asthma. In particular, several viruses such as
      respiratory syncytial virus, rhinovirus and influenza/parainfluenza viruses may
      favour the expression of the asthmatic phenotype, being also implicated in the
      induction of disease exacerbations. Within this pathological context, a
      significant role can also be played by airway bacterial colonizations and
      infections due to Chlamydiae and Mycoplasms. All these microbial agents probably
      interfere with complex immunological pathways, thus contributing to induce and
      exacerbate asthma in genetically predisposed individuals.

PMID- 16289786
TI  - Challenges for the adoption of evidence-based maternity care in Turkey.
AB  - Evidence-based medicine is an important tool for improving the quality of
      maternity care. However, getting providers to change their practices may not be
      an easy or rapid process, and other factors, in addition to knowledge of the
      literature, may be important. This study documents the current state of obstetric
      practices at three maternity hospitals in Istanbul, Turkey, and identifies
      attitudes, social pressures, and perceptions that, according to the theory of
      planned behavior, may pose challenges for adoption of evidence-based practices.
      Data were collected through interviews with administrators, examination of
      hospital statistics, provider and client interviews, and structured observations
      of maternity care. Practices that did not follow current guidelines included
      routine episiotomy, not allowing companionship during labor, use of procedures to
      speed up labor without indications, routine enema, restriction of mobility,
      restriction of oral fluids, supine position for delivery, and non-use of active
      management of the third stage of labor. The findings indicate that providers had
      negative attitudes about some recommended practices, while they had positive
      attitudes towards some ineffective and/or harmful practices. We identified social
      pressure to comply with practices recommended by supervisors and peers, as well
      as the belief that limited resources affect maternity care providers,
      opportunities to perform evidence-based procedures. An underlying problem was the
      failure to involve women in decision-making regarding their own maternity care.
      In addition to informing providers about the evidence, it seems necessary to
      develop standard protocols, improve physical conditions, and implement behavior
      interventions that take into account provider attitudes, social pressures, and
      beliefs.

PMID- 16289787
TI  - On being at higher risk: a qualitative study of prenatal screening for
      chromosomal anomalies.
AB  - This paper explores the meaning of higher risk status to women undergoing
      prenatal maternal screening for chromosomal anomalies. Quotations from lightly
      structured interviews and transcripts of pre-screening consultations in suburban
      London are used to illustrate pregnant women's diverse responses to the offer of
      screening, and to entering, living with and exiting from higher risk status. Some
      women reject screening in order to avoid the psychosocial and medical risks
      associated with higher risk status, or because they rule out pregnancy
      termination. They may question the risk selection implicitly built into the
      provision of preventative systems for some health problems but not others. Women
      who screen at higher risk may challenge this designation by questioning the
      system-specific probability used to separate them from the lower risk population.
      However, some experience distress even when they appreciate the precautionary
      basis on which their higher risk designation is based. They may find
      disengagement from higher risk status difficult after a diagnostic test has ruled
      out chromosomal anomalies. The findings highlight the complexity of communicating
      risk information to pregnant women and other screened populations, and emphasise
      the need to support those living with higher risk status and the benefits of
      keeping the time lived with this status as short as possible.

PMID- 16289788
TI  - A study of neurocysticercosis in the foothills of the Himalayas.
AB  - OBJECTIVES: The present study was planned and carried out with the aim of
      determining the incidence of neurocysticercosis (NCC) among patients with
      clinically manifested neurological disorders attending the Himalayan Institute of
      Medical Sciences (HIMS) hospital. METHODS: Spanning a period of 18 months, serum
      samples of consecutively selected patients were screened by ELISA for the
      presence of anti-cysticercus antibodies after obtaining a detailed history.
      Physical examinations were performed along with routine hematological, stool and
      urine tests. All patients included in the study group were also subjected to
      radiological investigations such as CT scan/MRI/X-ray and/or ultrasonography.
      RESULTS: One hundred and three new patients were selected for the study group,
      with a male:female ratio of 2:1. Of these, 33 (32.0%) patients were positive for
      Taenia solium IgG antibodies in sera. Children in the 11-20 years age group were
      most affected (39.4%). Only 10 patients (30.3%) were found to be positive for ova
      in stool, which correlated well with the presence of multiple lesions in the
      central nervous system (p<0.01). Solitary lesions were more common (66.7%) than
      multiple lesions (33.3%) on radiological diagnosis by CT scan/MRI. CONCLUSIONS: A
      high incidence of neurocysticercosis in the region reflects the endemic presence
      of T. solium and advocates the practice of better hygiene, cooking methods and
      water filtration procedures for the prevention of infection.

PMID- 16289789
TI  - Co-composting solid swine manure with pine sawdust as organic substrate.
AB  - The main objectives of this work were to investigate the evolution of the
      principal physicochemical properties, i.e., bulk temperature, pH, electrical
      conductivity (EC), moisture content, total organic matter, total nitrogen and
      total phosphorus, in co-composting pine sawdust with increasing percentages of
      fresh solid swine manure, and thus to evaluate the most desirable manure
      proportion for producing organic substrates in consideration of the quality of
      the resulted compost. The composting was in four identical 100.5l lab vessels,
      using 5% each tea leaves and herb residues as conditioners. The swine manure was
      added in the trials at 20%, 30%, 40%, respectively, and was substituted in the
      control with 30% lake sludge corrected by 0.5% urea. The initial humidity of each
      treatment was 60+/-2%. While being aerated actively at approximately 0.3m(3)/min
      at intervals of 10 min/h, the mixture was composted for 29 days. The results
      indicated that N and P decomposition primarily occurred in the mesophilic phase,
      while organic carbon decomposed in the thermophilic phase and 30% swine manure
      with initial C/N ratio of about 40 was more desirable for composting organic
      substrates.

PMID- 16289791
TI  - Effect of inorganic fertilizer and farmyard manure on soil physical properties,
      root distribution, and water-use efficiency of soybean in Vertisols of central
      India.
AB  - A field experiment was conducted on a Vertisol for three consecutive years (1998
      2000) to study the effects of combined use of inorganic fertilizer (NPK) and
      organic manure (farmyard manure) on soil physical properties, water-use
      efficiency, root growth and yield of soybean [Glycine max (L.) Merr.] in a
      soybean-mustard cropping system. Application of 10 Mg farmyard manure and
      recommended NPK (NPK+FYM) to soybean for three consecutive years improved the
      organic carbon content of the surface (0-15 cm) soil from an initial value of 4.4
      g kg(-1) to 6.2 g kg(-1) and also increased seed yield and water-use efficiency
      by 103% and 76%, respectively, over the control. The surface (0-15 cm) soil of
      the plots receiving both farmyard manure and recommended NPK had larger mean
      weight diameter (0.50 mm) and a higher percentage of water stable aggregates
      (55%) than both the inorganically fertilized (NPK) (0.44 mm and 49%) and
      unfertilized control plots (0.41 mm and 45.4%). The saturated hydraulic
      conductivity (13.32 x 10(-6) m s(-1)) of the NPK+FYM treatment of the 0-7.5 cm
      depth was also significantly greater than that of the NPK (10.53 x 10(-6) m s(
      1)) and control (8.61 x 10(-6) m s(-1)) treatments. The lowest bulk density (1.18
      Mg m(-3)) in the 0-7.5 cm layer was recorded in NPK+FYM whereas it was highest in
      the control plots (1.30 Mg m(-3)). However, at sub-surface (22.5-30 cm) layer,
      fertilizer and manure application had little effect on bulk density and saturated
      hydraulic conductivity. Root length density (RLD) up to the 30 cm depth was
      highest in the NPK+FYM plots and it was 31.9% and 70.5% more than NPK and control
      plots. The RLD showed a significant and negative correlation (r=-0.88( * *)) with
      the penetration resistance.

PMID- 16289790
TI  - Transformation of organic matter during co-composting of pig manure with sawdust.
AB  - Co-composting of pig manure with sawdust was studied in order to characterize the
      organic transformation during the process, using both chemical and spectroscopic
      methods. Humic acids (HA) and fulvic acids (FA) were fractionated from immature
      and mature pig manure compost, and characterized. After 63 days of composting,
      the ratio of total organic carbon and soluble organic carbon decreased to a
      satisfactory low level and the solid and soluble C/N ratios decreased rapidly for
      the first 35 days before attaining a constant value, indicating compost maturity.
      Humification could be responsible for the increase in humic acid proportion
      during composting. The increase in the aromatic bonds after composting, as
      indicated by the reduction of C/H and C/O ratios of HA and FA, resulted in a more
      stabilized product. A substantial increase in high molecular weight compounds
      along with a small increase in low molecular weight compounds was found in mature
      compost. Moreover the HA also had more complex organic compounds at this stage.
      Fluorescence spectral analysis showed an increase in the maximum wavelength of HA
      associated with the contents of aromatic structures in solution. A decrease in
      relative absorbance of HA at 1160 cm(-1), 2950 cm(-1) and 2850 cm(-1) was seen in
      the FTIR spectra indicating the decomposition of complex organic constituents,
      into simpler ones. Increase in the aromatic compounds with higher stability could
      account for the relative increase in the absorbance of HA at 1650 cm(-1) and 1250
      cm(-1) of the mature compost. The composition of FA was not much altered,
      indicating most of the degradation of organic matter occurred in HA. Data from
      organic carbon, C/N ratio, elemental analysis, E(4)/E(6) ratio, gel
      chromatography, fluorescence and FTIR spectra indicated an increase in
      polycondensed structures and the presence of more stable organic matter in the
      mature compost.

PMID- 16289792
TI  - Batch separation of shredded bulky waste by gas-solid fluidized bed at laboratory
      scale.
AB  - A gas-solid fluidized bed separator using various bed materials was used to
      separate shredded municipal bulky waste (SBW). Using 290 microm glass beads as
      the bed material, the apparent density of the fluidized bed was 1.5 g/cm(3) and
      the SBW could be separated into combustibles such as wood, paper and plastics and
      incombustibles such as metals and glass. The overall efficiency (Newton's
      efficiency) of the separation was calculated to be 0.93. In order to obtain high
      efficiency, the superficial velocity must be adjusted so that the fluidized bed
      is agitated moderately and at the same time there is no weak fluidized region.
      Using a mixture of particles of nylon shot and 68 microm glass beads, the
      apparent density of the fluidized mixture bed could be varied between 0.63 and
      0.99 g/cm(3) by changing the mixing ratio of the two materials. In the case of a
      mixing ratio of 20% for glass beads, an apparent density of 0.65 g/cm(3) was
      produced, in which wood and paper components were recovered while plastics
      remained in the bed to give a final overall efficiency of 0.88.

PMID- 16289793
TI  - The effect of dynamic scheduling and routing in a solid waste management system.
AB  - Solid waste collection and hauling account for the greater part of the total cost
      in modern solid waste management systems. In a recent initiative, 3300 Swedish
      recycling containers have been fitted with level sensors and wireless
      communication equipment, thereby giving waste collection operators access to real
      time information on the status of each container. In this study, analytical
      modeling and discrete-event simulation have been used to evaluate different
      scheduling and routing policies utilizing the real-time data. In addition to the
      general models developed, an empirical simulation study has been performed on the
      downtown recycling station system in Malmoe, Sweden. From the study, it can be
      concluded that dynamic scheduling and routing policies exist that have lower
      operating costs, shorter collection and hauling distances, and reduced labor
      hours compared to the static policy with fixed routes and pre-determined pick-up
      frequencies employed by many waste collection operators today. The results of the
      analytical model and the simulation models are coherent, and consistent with
      experiences of the waste collection operators.

PMID- 16289794
TI  - Organics removal from landfill leachate and activated sludge production in SBR
      reactors.
AB  - This study is aimed at estimating organic compounds removal and sludge production
      in SBR during treatment of landfill leachate. Four series were performed. At each
      series, experiments were carried out at the hydraulic retention time (HRT) of 12,
      6, 3 and 2d. The series varied in SBR filling strategies, duration of the mixing
      and aeration phases, and the sludge age. In series 1 and 2 (a short filling
      period, mixing and aeration phases in the operating cycle), the relationship
      between organics concentration (COD) in the leachate treated and HRT was pseudo
      first-order kinetics. In series 3 (with mixing and aeration phases) and series 4
      (only aeration phase) with leachate supplied by means of a peristaltic pump for
      4h of the cycle (filling during reaction period) - this relationship was zero
      order kinetics. Activated sludge production expressed as the observed coefficient
      of biomass production (Y(obs)) decreased correspondingly with increasing HRT. The
      smallest differences between reactors were observed in series 3 in which Y(obs)
      was almost stable (0.55-0.6 mg VSS/mg COD). The elimination of the mixing phase
      in the cycle (series 4) caused the Y(obs) to decrease significantly from 0.32 mg
      VSS/mg COD at HRT 2d to 0.04 mg VSS/mg COD at HRT 12d. The theoretical yield
      coefficient Y accounted for 0.534 mg VSS/mg COD (series 1) and 0.583 mg VSS/mg
      COD (series 2). In series 3 and 4, it was almost stable (0.628 mg VSS/mg COD and
      0.616 mg VSS/mg COD, respectively). After the elimination of the mixing phase in
      the operating cycle, the specific biomass decay rate increased from 0.006 d(-1)
      (series 3) to 0.032 d(-1) (series 4). The operating conditions employing
      mixing/aeration or only aeration phases enable regulation of the sludge
      production. The SBRs operated under aerobic conditions are more favourable at a
      short hydraulic retention time. At long hydraulic retention time, it can lead to
      a decrease in biomass concentration in the SBR as a result of cell decay. On the
      contrary, in the activated sludge at long HRT, a short filling period and
      operating cycle of the reactor with the mixing and aeration phases seem the most
      favourable.

PMID- 16289796
TI  - The development and preliminary validation of the Profile of Chronic Pain:
      Extended Assessment Battery.
AB  - The aim of the present research was the development and validation of a set of
      instruments, collectively called the Profile of Chronic Pain: Extended Assessment
      Battery (PCP:EA), designed to be administered to adults (between the ages of 25
      to 80) after establishing the existence of a chronic pain problem. The final 86
      item version of the PCP:EA consisted of 33 single items assessing: pain location
      and severity, pain characteristics (e.g. worst daily pain), medication use,
      health care status, the identity of the most important person in the patient's
      life, and functional limitations in 10 areas of daily living. In addition, the
      PCP:EA includes 13 multi-item subscales addressing aspects of coping (guarding,
      ignoring, task persistence, and positive self-talk), catastrophizing, pain
      attitudes and beliefs (including disability beliefs, belief in a medical cure for
      pain, belief in pain control, and pain-induced fear), and positive (tangible and
      emotional) and negative (insensitivity and impatience) social responses. Data
      were obtained from two national samples which were recruited and screened via a
      random-digit dialing telephone interview procedure. Stratified sampling was
      employed to assure equal gender and age group representation across three age
      groupings (25-44; 45-64; 65-80). Two survey studies provided strong evidence for
      the hypothesized factor structure, internal consistency, independence from
      response bias, and validity of the PCP:EA. Moreover, the presence of normative
      data enhance the diagnostic and prescriptive utility of the instrument.

PMID- 16289795
TI  - Multilevel analysis of couple congruence on pain, interference, and disability.
AB  - Couple congruence on ratings of pain severity and disability were examined using
      hierarchical linear modeling. Older community Individuals with Chronic Pain
      (ICPs) and their spouses completed the Multidimensional Pain Inventory (pain
      severity, interference, negative spouse responses to pain), Sickness Impact
      Profile (physical disability, psychosocial disability), and the Mood and Anxiety
      Symptom Questionnaire (psychological distress). Both spouses reported on ICPs'
      pain and disability as well as their own psychological distress. Spousal
      incongruence was observed on interference and physical disability such that ICPs
      reported greater disability than their spouses reported for them. No significant
      incongruence was observed in pain severity or psychosocial disability. Predictors
      of couples' mean ratings of pain and disability were identified. Specifically,
      couples in which the ICP was female reported higher couples' ratings of pain
      severity and interference. ICP distress was related to higher couples' ratings of
      all pain and disability variables whereas spouse distress was related to higher
      psychosocial disability ratings. ICPs' perceptions of negative spouse responses
      were also positively associated with couples' ratings of physical and
      psychosocial disability. In terms of congruence, ICP distress was associated with
      incongruence on interference, physical disability, and psychosocial disability
      whereas spouse distress predicted incongruence on pain severity, and
      interference. This study suggests that understanding couples' pain outcome
      ratings involves an awareness of factors that might influence their perceptions
      and behaviors.

PMID- 16289797
TI  - Why is a treatment aimed at psychosocial factors not effective in patients with
      (sub)acute low back pain?
AB  - Psychosocial factors have been shown to play an important role in the development
      of chronic low back pain (LBP). In our recently completed cluster-randomized
      trial we found, however, no evidence of an effect of our minimal intervention
      strategy (MIS) aimed at psychosocial factors, over usual care (UC) in patients
      with (sub)acute LBP. To explore the reasons why, this paper presents an
      evaluation of the processes presumably underlying the effectiveness of MIS.
      General practitioner (GP) attitude was evaluated by the Pain Attitudes and
      Beliefs Scale and two additional questions. GP behaviour was evaluated by
      analysing treatment registration forms and patients' responses to items regarding
      treatment content. Patients also scored items on satisfaction and compliance.
      Modification of psychosocial measures was evaluated by analysing changes after 6
      and 52 weeks on the Fear Avoidance and Beliefs Questionnaire, the Coping
      Strategies Questionnaire and the 4-Dimensional Symptom Questionnaire. A total of
      60 GPs and 314 patients participated in the study. GPs in the MIS-group adopted a
      less biomedical orientated attitude than in the UC-group, but were only
      moderately successful in identification of psychosocial factors. Treatment
      contents as perceived by the patient and patient satisfaction differed
      significantly between both groups. Changes on psychosocial measures, however, did
      not differ between groups. The suboptimal identification of psychosocial factors
      in the MIS-group and the absence of a relevant impact on psychosocial factors may
      explain why MIS was not more effective than UC.

PMID- 16289798
TI  - Activation of CB1 and CB2 receptors attenuates the induction and maintenance of
      inflammatory pain in the rat.
AB  - The aim of the present study was to investigate the effects of cannabinoid
      agonists on established inflammatory hyperalgesia. We have compared the effects
      of pre-administration versus post-administration of a potent non-selective
      cannabinoid agonist HU210 and a selective CB2 receptor agonist JWH-133 on hindpaw
      weight bearing and paw oedema in the carrageenan model of inflammatory
      hyperalgesia. For comparative purposes we also determined the effects of the mu
      opioid receptor agonist morphine and the COX2 inhibitor rofecoxib in this model.
      At 3 h following intraplantar injection of carrageenan (2%, 100 microl) there was
      a significant (P < 0.001) reduction in weight bearing on the ipsilateral hindpaw,
      compared to vehicle treated rats and a concomitant increase in ipsilateral
      hindpaw volume (P < 0.001), compared to vehicle treated rats. Systemic
      administration of HU210 (10 microg/kg) and JWH-133 (10 mg/kg) at 3 h following
      injection of carrageenan, significantly attenuated decreases in ipsilateral
      hindpaw weight bearing (P < 0.05 for both) and paw volume (P < 0.001 for both).
      Pre-administration of HU210 and JWH-133 had similar effects on weight bearing in
      this model. Pre-administered HU210 also significantly decreased carrageenan
      induced changes in paw volume (P < 0.001), this was not the case for JWH-133.
      Effects of post-administered HU210 and JWH-133 on ipsilateral hindpaw weight
      bearing and paw volume were comparable to the effect of systemic post
      administration of morphine and rofecoxib (3 mg/kg for both). In summary, both
      HU210 and JWH-133 attenuated established inflammatory hypersensitivity and
      swelling, suggesting that cannabinoid-based drugs have clinical potential for the
      treatment of established inflammatory pain responses.

PMID- 16289799
TI  - Anxiety and depression associated with migraine: influence on migraine subjects'
      disability and quality of life, and acute migraine management.
AB  - Anxiety and depression are reported to be frequently associated with migraine but
      how they impact on migraine-related disability, migraine subjects' quality of
      life, and medical and therapeutic management of migraine attacks has not been
      investigated. FRAMIG 3 is a nation-wide population-based postal survey carried
      out in France according to the 2004 international classification of headache
      disorders. Subjects who had had migraine attacks during the last 3 months
      (subjects with 'active migraine', N = 1957) were analysed for migraine-related
      disability (MIDAS score), quality of life (SF-12 questionnaire), and anxiety and
      depression (Hospital Anxiety and Depression Scale [HADS]) in comparison with non
      migraine subjects (N = 8287). Survey results indicate that 50.6% of subjects with
      active migraine were anxious and/or depressive (28.0% had anxiety alone, 3.5%
      depression alone, and 19.1% both anxiety and depression; P < or = 0.01 versus non
      migraine subjects for anxiety alone and combined anxiety and depression, NS for
      depression alone). Although, migraine-associated anxiety and depression do not
      appear to influence the drugs taken by migraine subjects for the acute treatment
      of migraine attacks, perceived treatment efficacy and satisfaction with treatment
      are lower in subjects with anxiety alone or combined with depression than in
      subjects with neither anxiety nor depression. Anxiety and depression should be
      systemically looked for and cared for in subjects consulting for migraine.

PMID- 16289800
TI  - Activation of the spinal ERK signaling pathway contributes naloxone-precipitated
      withdrawal in morphine-dependent rats.
AB  - Extracellular signal-regulated kinase (ERK), a mitogen-activated protein kinases
      (MAPK), transduces a broad range of extracellular stimuli into diverse
      intracellular responses. Recent studies have showed that ERK activation in the
      supraspinal level involved in the development of drug dependence, especially in
      psychological dependence. In this study, we reported that the spinal ERK
      signaling pathway was activated by chronic morphine injection. There was a
      further increase in ERK activation after naloxone-precipitated withdrawal.
      Furthermore, attenuation of the spinal ERK phosphorylation by intrathecal a MAPK
      kinase (MEK) inhibitor U0126 or knockdown of the spinal ERK by antisense
      oligonucleotides not only decreased the scores of morphine withdrawal, but also
      attenuated withdrawal-induced allodynia, which were accompanied by decreased ERK
      phosphorylation in the spinal cord. The spinal ERK inhibition or knockdown also
      reduced morphine withdrawal-induced phosphorylation of cAMP response element
      binding protein (CREB), which is one of the important downstream substrates of
      ERK pathway, and Fos expression. The involvement of the spinal ERK in morphine
      withdrawal was supported by our finding that intrathecal N-methyl-D-aspartate
      receptor antagonist MK-801 or protein kinase C inhibitor chelerythrine chloride
      suppressed withdrawal-induced ERK activation in the spinal cord and attenuated
      morphine withdrawal symptoms. These findings suggest activation of the spinal ERK
      signaling pathway contributes naloxone-precipitated withdrawal in morphine
      dependent rats.

PMID- 16289801
TI  - Cortical representation of experimental tooth pain in humans.
AB  - Cortical processing of electrically induced pain from the tooth pulp was studied
      in healthy volunteers with fMRI. In a first experiment, cortical representation
      of tooth pain was compared with that of painful mechanical stimulation to the
      hand. The contralateral S1 cortex was activated during painful mechanical
      stimulation of the hand, whereas tooth pain lead to bilateral activation of S1.
      The S2 and insular region were bilaterally activated by both stimuli. In S2, the
      center of gravity of the activation during painful mechanical stimulation was
      more medial/posterior compared to tooth pain. In the insular region, tooth pain
      induced a stronger activation of the anterior and medial parts. The posterior
      part of the anterior cingulate gyrus was more strongly activated by painful
      stimulation of the hand. Differential activations were also found in motor and
      frontal areas including the orbital frontal cortex where tooth pain lead to
      greater activations. In a second experiment, we compared the effect of weak with
      strong tooth pain. A significantly greater activation by more painful tooth
      stimuli was found in most of those areas in which tooth pain had induced more
      activation than hand pain. In the medial frontal and right superior frontal gyri,
      we found an inverse relationship between pain intensity and BOLD contrast. We
      concluded that tooth pain activates a cortical network which is in several
      respects different from that activated by painful mechanical stimulation of the
      hand, not only in the somatotopically organized somatosensory areas but also in
      parts of the 'medial' pain projection system.

PMID- 16289802
TI  - Pain-related emotions modulate experimental pain perception and autonomic
      responses.
AB  - The effect of emotions on pain perception is generally recognized but the
      underlying mechanisms remain unclear. Here, emotions related to pain were induced
      in healthy volunteers using hypnosis, during 1-min immersions of the hand in
      painfully hot water. In Experiment 1, hypnotic suggestions were designed to
      induce various positive or negative emotions. Compared to a control condition
      with hypnotic-relaxation, negative emotions produced robust increases in pain. In
      Experiment 2, induction of pain-related anger and sadness were found to increase
      pain. Pain increases were associated with increases in self-rated desire for
      relief and decreases in expectation of relief, and with increases in arousal,
      negative affective valence and decreases in perceived control. In Experiment 3,
      hypnotic suggestions specifically designed to increase and decrease the desire
      for relief produced increases and decreases in pain, respectively. In all three
      experiments, emotion-induced changes in pain were most consistently found on
      ratings of pain unpleasantness compared to pain intensity. Changes in pain-evoked
      cardiac responses (R-R interval decrease), measured in experiments 2 and 3, were
      consistent with changes in pain unpleasantness. Correlation and multiple
      regression analyses suggest that negative emotions and desire for relief
      influence primarily pain affect and that pain-evoked autonomic responses are
      strongly associated with pain affect. These results confirm the hypothesized
      influence of the desire for relief on pain perception, and particularly on pain
      affect, and support the functional relation between pain affect and autonomic
      nociceptive responses. This study provides further experimental confirmation that
      pain-related emotions influence pain perception and pain-related physiological
      responses.

PMID- 16289803
TI  - Intersession coping skill practice mediates the relationship between readiness
      for self-management treatment and goal accomplishment.
AB  - Underlying pain self-management treatments is the expectation that patients must
      adhere to coping skill practice recommendations to obtain treatment benefits.
      Recently, a model of motivation for pain treatment has proposed that patients'
      readiness to adopt a self-management approach serves as a predictor of active
      participation in treatment, and ultimately, of improved outcomes. This study
      compared the ability of pain readiness to change, as measured by the Pain Stages
      of Change Questionnaire (PSOCQ), and self-efficacy (SE) ratings, to predict
      adherence and goal accomplishment in cognitive-behavioral therapy (CBT) for
      chronic pain. Further analyses tested the hypothesis that adherence mediated the
      relationship between readiness to change and goal accomplishment. Data were
      collected as part of a larger randomized controlled trial of primary care based
      CBT. Participants were 78 patients recruited from a VA primary care clinic. At
      pre-treatment Ss completed the PSOCQ to assess readiness to adopt a self
      management approach to chronic pain and an SE measure to quantify certainty of
      achieving up to five behavioral treatment goals. Criteria were means of
      aggregated intersession adherence ratings and mean post-treatment goal
      accomplishment ratings. Pre-treatment PSOCQ variables significantly predicted
      intersession adherence and goal accomplishment. SE did not significantly predict
      either criterion. The statistical relationship between pre-treatment PSOCQ and
      behavioral goal accomplishment was significantly attenuated when intersession
      adherence was taken into account. These data provide support for a motivational
      model of pain treatment that asserts adherence to therapist recommendations for
      coping skill practice mediates readiness to change and self-reported goal
      attainments.

PMID- 16289804
TI  - Facing others in pain: the effects of empathy.

PMID- 16289805
TI  - Improvement of leaching process of Geniposide with ultrasound.
AB  - The effect of ultrasound on the leaching process, in which Geniposide is leached
      from the Gardenia fruit by deionized water at 20 degrees C, was investigated. The
      phase equilibrium and the dynamics were measured at static, stirring, and
      ultrasonically assisted conditions, respectively. The experimental results show
      that the extraction yield of Geniposide with ultrasound at 0.1533 W cm(-2), is
      increased by 16.5%, in comparison with that without ultrasound when the ratio of
      the solvent volume to the fruit weight is 40 ml/g. A model for mass transfer,
      based on the intraparticle diffusion and the external mass transfer, was
      developed. And the dynamic curves calculated by the model are in a good agreement
      with the experimental data. The external mass transfer coefficient k(f)/R and
      intraparticle diffusion coefficient D(e)/R2 were obtained by fitting of the
      experiment data. The external mass transfer coefficient with ultrasound at 0.1533
      W cm(-2) is 1.63 times higher than that in static process, and the intraparticle
      diffusion coefficient with ultrasound at 0.1533 W cm(-2) is 3.25 times higher
      than that in static process.

PMID- 16289806
TI  - Effect of ultrasound on adsorption of Geniposide on polymeric resin.
AB  - The effects of pulse ultrasound with different pulse parameter on the adsorption
      isotherm and kinetics of Geniposide on Resin 1300 were studied. And the mass
      transfer model describing the adsorption process was constructed. Amount of
      Geniposide adsorbed on Resin 1300 in the presence of ultrasound is lower than
      that in the absence of ultrasound. At our experimental conditions, the adsorption
      equilibrium constant decreases with increasing ultrasonic intensity and pulse
      duty ratio, and with decreasing pulse period. In addition, pulse ultrasound can
      enhance both liquid film diffusion and intraparticle diffusion, and the
      intensification of liquid film diffusion with pulse ultrasound is stronger than
      that of intraparticle diffusion. The intraparticle diffusion coefficient D(e)/R2
      increases with increasing ultrasonic intensity and pulse duty ratio, and with
      decreasing pulse period.

PMID- 16289807
TI  - Study of ultrasonic melt treatment on the quality of horizontal continuously cast
      Al-1%Si alloy.
AB  - The fluctuation of the melt temperature in a tundish was measured during casting
      and experiments were conducted to investigate the effects of ultrasonic melt
      treatment on the surface quality and solidification structures of Al-1%Si ingots.
      The results show that the uniformity of melt temperature was enhanced with the
      application of ultrasonic melt treatment. When the ultrasonic power is 1,000W,
      the surface quality was evidently improved and grains of cast ingots were
      refined. Moreover, EPMA analysis was adopted to study the relationship between
      the ultrasonic power and boundary segregation of Si element. The result shows
      that boundary segregation is suppressed with the increase of ultrasonic power and
      the phenomenon was theoretically interpreted.

PMID- 16289808
TI  - Gene expression analysis of urethane-induced lung tumors in ras H2 mice.
AB  - In our previous study, microarray analysis was performed on N-ethyl-N-nitrosourea
      (ENU)-induced forestomach tumors in transgenic mice carrying the human prototype
      c-Ha-ras gene (ras H2 mice). Ras-MAPK related genes, including the transgene and
      mouse endogenous ras genes, that are involved in enhanced carcinogenesis were up
      regulated in these tumors. In the present study, ras H2 mice received five
      intraperitoneal injections of 1,000 mg/kg urethane at 2-day intervals.
      Subsequently, microarray and RT-PCR analyses for the transgene and some molecules
      involved in the Ras pathway were performed on the induced lung tumors. In the
      microarray analysis, gene expression profiles of normal lungs and adenomas showed
      a distinct pattern, and several genes related to the cell cycle and nucleotide
      metabolism were up-regulated in the adenomas. RT-PCR confirmed the overexpression
      of the transgene in lung tumors; however, the up-regulation of the mouse
      endogenous ras genes was not observed. Some genes showed a similar expression
      pattern in both ENU- and urethane-induced tumors. These results suggest that the
      overexpression of the transgene plays an important role in the carcinogenesis of
      both ENU- and urethane-induced tumors in ras H2 mice. The genes that showed a
      similar expression pattern in both tumors were considered to be the candidate
      genes responsible for enhanced carcinogenesis.

PMID- 16289810
TI  - Eta4-pyrone iron(0)carbonyl complexes as effective CO-releasing molecules (CO
      RMs).
AB  - The CO-releasing properties of iron(0)tricarbonyl complexes bearing a 2-pyrone
      ligand have been evaluated. In this report, we demonstrate that the intrinsic
      stability of the (eta4-2-pyrone)Fe(CO)3 complex influences the extent and rate of
      CO release, which is affected by the presence of a halogen substituent on the 2
      pyrone ring. The cell viability index has been highlighted for the active carbon
      monoxide-releasing molecules (CO-RMs), demonstrating that these complexes and
      related derivatives are a promising new class of compounds with potential
      therapeutic applications.

PMID- 16289809
TI  - Valproic acid monotherapy induces DNA oxidative damage.
AB  - Valproic acid (VPA) and 8-hydroxy-2-deoxyguanosine (8-OHdG) are implicated with
      the free radicals production. We aimed to evaluate total oxidant status (TOS) and
      8-OHdG in children on VPA monotherapy. Fifty patients with seizures, mean age
      8.5+/-3.6 years, were divided into group A (N=26) and group B (N=24) with VPA
      serum levels 81.0+/-8.0 and 114+/-9.7 microg/mL, respectively. Thirty healthy
      children were the controls. Liver function tests and lipids were determined with
      routine methods, TOS and 8-OHdG with commercial kits, after 60 days on VPA
      therapy. Liver function parameters, lipids, TOS (647+/-43 micromol/L) and 8-OHdG
      (0.49+/-0.08 ng/mL) were significantly higher in group B than those in group A
      (580+/-40 micromol/L, 0.37+/-0.04 ng/mL, p<0.001) and controls (124+/-30
      micromol/L, 0.11+/-0.04 ng/mL, p<0.001, respectively). Significant correlation
      coefficients were found between 8-OHdG versus TOS (r=0.67, p<0.001) and 8-OHdG
      versus VPA (r=0.60, p<0.001) levels. It is suggested that VPA impairs the liver
      function resulting in free radicals production. The latter seems to produce DNA
      oxidative damage in liver cells, not excluding neuronal cells, as evidenced by
      the measured remarkably increased 8-OHdG serum levels. 8-OHdG evaluation may be a
      useful biomarker to follow up the increased risk of degeneration process in VPA
      patients.

PMID- 16289811
TI  - The discovery of fluoropyridine-based inhibitors of the factor VIIa/TF complex-
      Part 2.
AB  - The activated factor VII/tissue factor complex (FVIIa/TF) is known to play a key
      role in the formation of blood clots. Inhibition of this complex may lead to new
      antithrombotic drugs. A fluoropyridine-based series of FVIIa/TF inhibitors was
      discovered which utilized a diisopropylamino group for binding in the S2 and S3
      binding pockets of the active site of the enzyme complex. In this series, an
      enhancement in binding affinity was observed by substitution at the 5-position of
      the hydroxybenzoic acid sidechain. An X-ray crystal structure indicates that
      amides at this position may increase inhibitor binding affinity through
      interactions with the S1'/S2' pocket.

PMID- 16289812
TI  - Synthesis and antibacterial activity of 3-O-acyl-6-O-carbamoyl erythromycin A
      derivatives.
AB  - A series of 3-O-acyl-6-O-carbamoyl erythromycin A derivatives has been
      synthesized. Several functional groups were identified as the optimal C3
      substituents, and the best compounds in this series possess potent in vitro
      antibacterial activity against erythromycin-susceptible and erythromycin
      resistant bacteria.

PMID- 16289813
TI  - Intermolecular interactions in the crystal structures of potential HIV-1
      integrase inhibitors.
AB  - 2-[(2,5-dichloro-4-nitro-phenylamino)-methoxy-methyl]-8-hydroxy-quinoline 1 and 2
      methyl-quinoline-5,8-dione-5-oxime 2 were obtained as potential HIV-1 integrase
      inhibitors and analyzed by X-ray crystallography. Semiempirical theoretical
      calculations of energy preferred conformations were also carried out. The crystal
      structures of both compounds are stabilized via hydrogen bonds and pi-pi stacking
      interactions. The planarity of compound 1 is caused by intramolecular hydrogen
      bonds.

PMID- 16289814
TI  - Indoloprodigiosins from the C-10 bipyrrolic precursor: new antiproliferative
      prodigiosin analogs.
AB  - The condensation of the C-10 methoxybipyrrole precursor (3) of prodigiosin with
      indoles and a related pyrrole derivative yields novel analogs of prodigiosin.
      Biological evaluation of these products revealed compounds that inhibit cancer
      cell proliferation from 50 nM to 50 microM.

PMID- 16289816
TI  - Design and synthesis of cyclic and linear peptide-agarose tools for baiting
      interacting protein partners of GPCRs.
AB  - A ligation strategy for the synthesis of cyclic and linear peptides covalently
      linked to agarose beads designed as baits to identify new interacting partners of
      intracellular loops of the V2 vasopressin receptor, a member of the G-protein
      coupled receptor family, is reported. The peptide-resin conjugates were
      subsequently shown to interact specifically with a fraction of proteins present
      in cellular lysates.

PMID- 16289815
TI  - A novel nicotinic acetylcholine receptor antagonist radioligand for PET studies.
AB  - Using positron emission tomography (PET) with a specific and selective
      radioligand targeting nicotinic acetylcholine receptor (nAChR) would allow us to
      better understand various nAChR related CNS disorders. The use of radiolabeled
      nAChR antagonists would provide a much safer pharmacological profile, avoiding
      most peripheral side effects that might be generated from radiolabeled nAChR
      agonists even at the tracer level; thus, PET imaging with nAChR antagonists would
      facilitate clinical application. A potent and selective nAChR antagonist was
      labeled and characterized with PET in non-human primates. Its high brain uptake,
      high signal-to-noise ratio, and high specific binding strongly suggest a great
      potential to carry out imaging studies in humans. In addition, the use of a C-11
      radiotracer would allow us to perform multiple PET studies in the same individual
      within a short time frame. The presence of an iodine atom in the molecule also
      allows the possibility to label with radioiodine for SPECT studies.

PMID- 16289817
TI  - Piperazinyl oxime ethers as NK-1 receptor antagonists.
AB  - The synthesis and structure-activity relations for a new class of centrally
      active NK-1 receptor antagonists are described. The new compounds are based on
      piperazine 2 and contain an oxime ether functionality. Several new compounds have
      high affinity for the NK-1 receptor and show good antagonistic activity in the
      gerbil foot-tapping assay.

PMID- 16289818
TI  - Guiding farnesyltransferase inhibitors from an ECLiPS library to the catalytic
      zinc.
AB  - Farnesyltransferase inhibitors identified from an ECLiPS library were optimized
      using solution-phase synthesis. X-ray crystallography of inhibited complexes was
      used to identify substructures that coordinate to the active site zinc. The X-ray
      structures were ultimately used to guide the design of second-generation analogs
      with FTase IC(50)s of less than 1.0 nM.

PMID- 16289819
TI  - 6-Acylamino-2-amino-4-methylquinolines as potent melanin-concentrating hormone 1
      receptor antagonists: structure-activity exploration of eastern and western
      parts.
AB  - SAR explorations of the eastern and western parts of recently disclosed 2
      aminoquinoline MCH1R-antagonists are reported. Eastern part investigations
      confirmed a high degree of structural freedom, and a number of additional single
      digit nanomolar antagonists were identified. Investigations of the western part
      also confirmed the initial SAR analysis, requiring a para-substituted phenyl ring
      spaced from the 6-amide by two connecting atoms. The exploration led to the
      discovery of a novel sub-series with a 4-biphenylcarboxamide western part, also
      exhibiting single digit nanomolar affinity.

PMID- 16289821
TI  - Cytotoxicity of novel derivatives of the spin trap EMPO.
AB  - Free radicals are involved in different regulatory and pathological processes.
      The formation of superoxide in living cells or whole organisms is of major
      interest. ESR spin trapping allows identification of the radicals if proper spin
      traps are available. Our study investigates the toxicity of novel derivatives of
      the spin trap EMPO to cultured human lung carcinoma cells (A549), breast
      carcinoma cells (SKBR3), colon carcinoma cells (SW480) as well as to human
      fibroblasts (F2000). A dose-dependent decrease of the cell number was observed
      for all spin traps. At 100mM BuMPO, t-BuMPO and s-BuMPO caused pronounced cell
      loss (>90%) and increased LDH-release, while DEPMPO, EMPO, PrMPO and i-PrMPO
      caused only moderate cell loss (<60%) without any effect on the LDH-release after
      24h. At 10mM and 50mM the latter agents even decreased LDH-release. 10mM and 50mM
      of i-PrMPO as well as 10mM PrMPO increased intracellular GSH content acting like
      antioxidants, whereas 50mM s-BuMPO and PrMPO decreased GSH content by 67% and
      38%, respectively. Staining for apoptotic nuclei did not reveal any differences
      between controls and treated cultures indicating necrotic cell death possibly due
      to membrane toxicity. The following toxicity ranking was obtained: t
      BuMPO>BuMPO>s-BuMPO>PrMPO>i-PrMPO approximately DEPMPO approximately EMPO. The
      least toxic compounds were DEPMPO (LD(50)=143 mM for SW480, 117 mM for A549 or
      277 mM for F2000) and i-PrMPO (LD(50)=114 mM for SKBR3), the most toxic one was t
      BuMPO (LD(50)=5-6mM for all cell types). In conclusion, up to 50mM i-PrMPO
      (t(1/2)=18.8 min) and up to 10 mM s-BuMPO (t(1/2)=26.3 min) can be recommended
      for further investigation of superoxide in biological systems.

PMID- 16289822
TI  - Kinetic investigation on aqueous decomposition of 2-chloroethylnitrososulfamide.
AB  - The kinetics decomposition of 2-chloroethylnitrososulfamides (CENS) was studied
      in aqueous buffered solutions with pH ranging from 0 to 14. The study was
      monitored by RP-LC-MS and conventional UV spectrophotometry. The reaction
      proceeded via a pseudo-first-order kinetic with significant correlation
      coefficient. The major decomposition products from CENS after incubation in
      phosphate buffer were isolated and identified by NMR and mass spectrometry. The
      results indicate that the mechanism pathway involves a denitrosation of the CENS
      and competitive hydrolysis with nucleophilic attack on the sulfur atom and
      formation of sulfamate compounds.

PMID- 16289820
TI  - Conversion of A3 adenosine receptor agonists into selective antagonists by
      modification of the 5'-ribofuran-uronamide moiety.
AB  - The highly selective agonists of the A(3) adenosine receptor (AR), Cl-IB-MECA (2
      chloro-N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine), and its 4'-thio
      analogue, were successfully converted into selective antagonists simply by
      appending a second N-methyl group on the 5'-uronamide position. The 2-chloro-5'
      (N,N-dimethyl)uronamido analogues bound to, but did not activate, the human
      A(3)AR, with K(i) values of 29 nM (4'-O) and 15 nM (4'-S), showing >100-fold
      selectivity over A(1), A(2A), and A(2B)ARs. Competitive antagonism was
      demonstrated by Schild analysis. The 2-(dimethylamino)-5'-(N,N-dimethyl)uronamido
      substitution also retained A(3)AR selectivity but lowered affinity.

PMID- 16289823
TI  - The electronic structure of human erythropoietin as an aid in the design of
      oxidation-resistant therapeutic proteins.
AB  - The electronic structure of human erythropoietin (HuEPO) has been investigated
      with the aid of quantum mechanical calculations. The results indicate that the
      protein is highly polarized and its permanent dipole moment has a magnitude of
      471 D. The HOMO of HuEPO is localized on Trp51, which stays in close proximity to
      Met54. Three oxidation-resistant mutants of HuEPO (W51F, M54V, and W51F-M54V)
      have been modeled and their electronic structures are compared to that of the
      native protein. Among them, the W51F mutation is predicted to be the most
      effective in increasing the oxidation potential of the protein.

PMID- 16289824
TI  - Anterior longitudinal ligament injuries in whiplash may lead to cervical
      instability.
AB  - Although whiplash injuries account for a significant annual cost to society, the
      exact mechanism of injury and affected tissues remain unknown. Previous
      investigations documented injuries to the cervical anterior longitudinal ligament
      in whiplash. The present investigation implemented a comprehensively validated
      computational model to quantify level-dependent distraction magnitudes of this
      structure in whiplash. Maximum ligament distractions approached failure levels,
      particularly in middle to lower cervical levels, and occurred during the initial
      phase of head-neck kinematics. In particular, the C5-C6 anterior longitudinal
      ligament sustained distraction magnitudes as high as 2.6mm during the retraction
      phase, corresponding to 56% of distraction necessary to result in ligament
      failure. Present results demonstrated that anterior structures in the lower
      cervical spine may be susceptible to injury through excess distraction during the
      retraction phase of whiplash, which likely occurs prior to head restraint
      contact. Susceptibility of these structures is likely due to non-physiologic
      loading placed on the cervical spinal column as the head translates posteriorly
      relative to the thorax. Injury to anterior spinal structures can result in
      clinical indications including cervical instability in extension, axial rotation,
      and lateral bending modes. Mitigation of whiplash injury may be achieved by
      minimizing head retraction during initial stages of whiplash.

PMID- 16289825
TI  - Stress-induced cortisol responses, sex differences, and false recollections in a
      DRM paradigm.
AB  - The current studies investigated whether acute stress potentiates false
      recollections (so-called "false memories") in a Deese-Roediger-McDermott (DRM)
      paradigm, and whether sex differences modulate these effects. Participants were
      assigned to either a stress (trier social stress test) or a control group.
      Subsequently, they were subjected to DRM word lists and probed for recall and
      recognition. Results showed no differences between the stress and control group
      on measures of false recollections (Study 1; N=60). Even though correct recall
      was impaired by acute stress, there were no differences between high or low
      cortisol responders and controls on false recall or recognitions rates (Study 2;
      N=92). These results suggest that cortisol responses do not directly potentiate
      false recollections. Neither in Study 1 nor in Study 2 did we find any evidence
      that the effects of cortisol on false recollections are different in men and
      women, although there was an indication that independent of stress men produced
      more commission errors.

PMID- 16289826
TI  - Wireless electrodeless piezomagnetic biosensor with an isolated nickel
      oscillator.
AB  - This study presents a fundamental concept of piezomagnetic biochemical sensor
      driven in a wireless-electrodeless manner. A stepped cylindrical rod of nickel is
      used as the oscillator, which traps the vibrational energy of axially-polarized
      surface-shear waves in the central part, where the diameter is slightly larger. A
      meander-line coil surrounding the oscillator with an air gap can cause and detect
      the resonant vibrations of the surface-shear waves via the piezomagnetic effect.
      The resonant frequency of the trapped-mode resonance is continuously measured to
      detect human immunoglobulin G (IgG). It decreased by 0.08% when a solution
      containing IgG was injected into the glass cell where the oscillator was placed
      alone. This oscillator is useful for fundamental studies of various biochemical
      reactions in a closed system in different environmental gases and different
      pressures.

PMID- 16289827
TI  - A biosensor based on co-immobilized L-glutamate oxidase and L-glutamate
      dehydrogenase for analysis of monosodium glutamate in food.
AB  - A monosodium glutamate (MSG) biosensor made by co-immobilized L-glutamate oxidase
      (L-GLOD) and L-glutamate dehydrogenase (L-GLDH) as the bio-component based on
      substrate recycling for highly sensitive MSG or L-glutamate determination, has
      been developed. Regeneration of MSG by substrate recycling provided an
      amplification of the sensor response. Higher signal amplification was found in
      the presence of ammonium ion. The sensor was standardized to determine MSG in the
      range of 0.02-3.0 mg/L. Linearity was obtained from 0.02 to 1.2 mg/L in presence
      of ammonium ion (10 mM) and NADPH (reduced nicotinamide adenine dinucleotide
      phosphate) (2 mM), but in absence of L-GLDH, the detection limit of MSG is
      confined to 0.1 mg/L. The apparent Km for MSG with L-GLOD-L-GLDH coupled reaction
      was 0.4451 mM but 1.9222 mM when only L-GLOD was immobilized. Cross linking with
      glutaraldehyde in the presence of bovine serum albumin (BSA) as a spacer molecule
      has been used for the method of immobilization. The response time of the sensor
      was 2 min. The optimum pH and temperature of the biosensor has been determined as
      7+/-2 and 25+/-2 degrees C, respectively. The enzyme immobilized on the membrane
      was used for over 50 measurements. The standard error of the sample measurement
      was 4-5%. The activity of the enzyme-immobilized membrane was tested over a
      period of 60 days.

PMID- 16289828
TI  - Deletion of the nuclear receptor Nr2e1 impairs synaptic plasticity and dendritic
      structure in the mouse dentate gyrus.
AB  - The spontaneous or targeted deletion of the nuclear receptor transcription factor
      Nr2e1 produces a mouse that shows hypoplasia of the hippocampal formation and
      reduced neurogenesis in adult mice. In these studies we show that hippocampal
      synaptic transmission appears normal in the dentate gyrus and cornu ammonis 1
      subfields of adult mice that lack Nr2e1 (Nr2e1-/-), and that fEPSP shape, paired
      pulse responses, and short-term plasticity are not substantially altered in
      either subfield. In contrast, the expression of long-term potentiation is
      selectively impaired in the dentate gyrus, and not in the cornu ammonis 1
      subfield. Golgi analysis revealed that there was a significant reduction in both
      dendritic branching and dendritic length that was specific to dentate gyrus
      granule cells in the Nr2e1-/- mice. These results indicate that Nr2e1 deletion
      can significantly alter both synaptic plasticity and dendritic structure in the
      dentate gyrus.

PMID- 16289829
TI  - Failure of MK-801 to suppress D1 receptor-mediated induction of locomotor
      activity and striatal preprotachykinin mRNA expression in the dopamine-depleted
      rat.
AB  - N-methyl-D-aspartate receptor antagonism exerts suppressive influences over
      dopamine D1 receptor-mediated striatal gene expression and locomotor behavior in
      the intact rat. The present study examined the effects of the N-methyl-D
      aspartate receptor antagonist MK-801 on locomotor activity and striatal
      preprotachykinin mRNA expression stimulated by the D1 agonist (+/-)6-chloro-7, 8
      dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide in
      rats with bilateral dopamine lesions. Two months after neonatal dopamine lesions
      with 6-hydroxydopamine, rats were challenged with (+/-)6-chloro-7, 8-dihydroxy-3
      allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (1.0 mg/kg) 15
      min after administration of the N-methyl-D-aspartate receptor antagonist MK-801
      (0.1 mg/kg). In the intact rat, MK-801 prevented the induction of striatal
      preprotachykinin mRNA by D1 agonism. Similarly, direct infusion of (+/-)6-chloro
      7, 8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide
      (3.0 microg) into the intact striatum produced an increase in locomotor activity
      that was suppressed by MK-801 (1.0 microg) co-infusion. In the dopamine-depleted
      rat, MK-801 (0.1 mg/kg) administered prior to (+/-)6-chloro-7, 8-dihydroxy-3
      allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (1.0 mg/kg)
      increased, rather than suppressed, striatal preprotachykinin mRNA levels.
      Intrastriatal infusion of MK-801 (1.0 microg) failed to inhibit D1-mediated
      induction of motor activity in dopamine-depleted animals. Together, these data
      provide further support that N-methyl-D-aspartate receptor antagonists lose their
      ability to block D1-mediated behavioral activation following dopamine depletion.
      The activation, rather than suppression, of tachykinin neurons of the direct
      striatonigral pathway may play a facilitatory role in this mechanism.

PMID- 16289830
TI  - Er81 is expressed in a subpopulation of layer 5 neurons in rodent and primate
      neocortices.
AB  - Laminar organization is a fundamental cytoarchitecture in mammalian CNS and a
      striking feature of the neocortex. ER81, a transcription factor, has recently
      been utilized as a marker of cells in the layer 5 of the neocortex. We further
      pursued the distribution of ER81 to investigate the identity of the ER81
      expressing cells in the brain. Er81 transcript was expressed in a subset of
      pyramidal cells that were scattered throughout the entire width of layer 5. In
      the rat cortex, Er81 transcripts were first detected in the ventricular zone at
      E15, remained expressed in putative prospective layer 5 neurons during infant and
      juvenile stages. The ER81-expressing subpopulation in adult layer 5 neurons did
      not segregate with the phenotypes of the projection targets. By retrograde
      labeling combined with immunohistochemistry or reverse transcription-polymerase
      chain reaction analysis, we found ER81 expression in nearly all of the layer 5
      neurons projecting to the spinal cord or to the superior colliculus, while in
      only one-third of the layer 5 neurons projecting to the contralateral cortex.
      Er81 was also detected in layer 5 neurons in a P2 Japanese macaque monkey but not
      in adult monkey cortices. These findings suggest that a neuron class defined by a
      molecular criterion does not necessarily segregate with that defined by an
      anatomical criterion, that ER81 is involved in cell differentiation of a subset
      of layer 5 projection neurons and that this mechanism is conserved among rodents
      and primates.

PMID- 16289831
TI  - In vitro thyroid hormone rapidly modulates protein phosphorylation in
      cerebrocortical synaptosomes from adult rat brain.
AB  - Thyroid hormones induced rapid changes in phosphorylation in a membrane
      containing lysate of synaptosomes purified from adult rat cerebral cortex. The in
      vitro addition of 3,5,3'-L-triiodothyronine or L-thyroxine strongly influenced
      incorporation of label from [gamma-32P]-ATP into proteins in a cerebrocortical
      synaptosomal lysate. Incubation with 3,5,3'-L-triiodothyronine or L-thyroxine had
      strong biphasic dose-dependent effects on the phosphorylation of 38+/-1, 53+/-1,
      62+/-1, and 113+/-1 kDa proteins (which we termed alpha, beta, gamma, and delta,
      respectively) and several others. Although we observed differing levels of
      phosphorylation among the four proteins, doses of 3,5,3'-L-triiodothyronine or L
      thyroxine ranging from 1 to 30 nM caused significant dose-dependent stimulation
      of the phosphorylation of all of them, an effect which occurred within three
      minutes. In each case, the enhancement of phosphorylation diminished with higher
      concentrations (100 nM-1 microM) of 3,5,3'-L-triiodothyronine. In contrast,
      incubations with similar doses of 3,3',5'-L-triiodothyronine (reverse L
      triiodothyronine) were without significant effect, indicating a specificity for
      3,5,3'-L-triiodothyronine and L-thyroxine. Western blots of synaptosomal lysates
      incubated with 3,5,3'-L-triiodothyronine (1 nM-1 microM) demonstrated
      phosphorylation at the serine residues of a 112 kDa protein (matching delta) and
      phosphorylation at tyrosyl residues of a distinct 95 kDa protein. These data
      support the contention that thyroid hormones have a variety of rapid nongenomic
      pathways for regulation of protein phosphorylation in mature mammalian brain.

PMID- 16289832
TI  - Synaptic activation of transient receptor potential channels by metabotropic
      glutamate receptors in the lateral amygdala.
AB  - Classical mammalian transient receptor potential channels form non-selective
      cation channels that open in response to activation of phospholipase C-coupled
      metabotropic receptors, and are thought to play a key role in calcium homeostasis
      in non-excitable cells. Within the nervous system transient receptor potential
      channels are widely distributed but their physiological roles are not well
      understood. Here we show that in the rat lateral amygdala transient receptor
      potential channels mediate an excitatory synaptic response to glutamate.
      Activation of group I metabotropic glutamate receptors on pyramidal neurons in
      the lateral amygdala with either exogenous or synaptically released glutamate
      evokes an inward current at negative potentials with a current voltage
      relationship showing a region of negative slope and steep outward rectification.
      This current is blocked by inhibiting G protein function with GTP-beta-S, by
      inhibiting phospholipase C or by infusing transient receptor potential antibodies
      into lateral amygdala pyramidal neurons. Using RT-PCR and Western blotting we
      show that transient receptor potential 1, transient receptor potential 4 and
      transient receptor potential 5 are present in the lateral amygdala. Single cell
      PCR confirms the presence of transient receptor potential 1 and transient
      receptor potential 5 in pyramidal neurons and we show by co-immunoprecipitation
      that transient receptor potential 1 and transient receptor potential 5 co
      assemble as a heteromultimers in the amygdala. These results show that in lateral
      amygdala pyramidal neurons synaptically released glutamate activates transient
      receptor potential channels, which we propose are likely to be heteromultimeric
      channels containing transient receptor potential 1 and transient receptor
      potential 5/transient receptor potential 4.

PMID- 16289833
TI  - Excitatory actions of synaptically released catecholamines in the rat lateral
      geniculate nucleus.
AB  - The gating properties of thalamic relay neurons are influenced by the actions of
      a variety of neuromodulators in concert with the intrinsic properties of these
      relay neurons. In this study, we have investigated the consequences of
      synaptically released catecholamines on the excitability of neurons in the rat
      dorsal lateral geniculate nucleus. Tetanic stimulation of the optic tract, in
      which catecholamine fibers also course near or through, produced a strong
      depolarization that consisted of a fast and slow component. The fast excitatory
      postsynaptic potential was attenuated by ionotropic glutamate receptor
      antagonists and further unmasked the slow excitatory postsynaptic potential. The
      amplitude of the slow excitatory postsynaptic potential was dependent on the
      frequency and intensity of the tetanic stimulation. The alpha1-adrenergic
      receptor antagonist, prazosin, and the D1-like dopamine receptor antagonist,
      SCH23390, attenuated the slow excitatory postsynaptic potential; however, the
      slow excitatory postsynaptic potential was unaltered by metabotropic glutamate,
      cholinergic, alpha2-adrenergic, and beta-adrenergic receptor antagonists. On the
      other hand, tetanic stimulation of the optic radiations (corticothalamic axons)
      evoked a slow excitatory postsynaptic potential that was completely attenuated by
      metabotropic glutamate receptor antagonists. Our results suggest that tetanic
      stimulation of catecholamine fibers within the optic tract produces synaptic
      release of norepinephrine and dopamine that in turn activates both alpha(1)
      adrenergic and D1-like dopamine receptors leading to a robust membrane
      depolarization. By altering the excitability of relay neurons, ascending
      activating systems may modulate the efficacy of information transfer through the
      thalamus.

PMID- 16289834
TI  - Perisaccadic mislocalization without saccadic eye movements.
AB  - Despite frequent saccadic gaze shifts we perceive the surrounding visual world as
      stable. It has been proposed that the brain uses extraretinal eye position
      signals to cancel out saccade-induced retinal image motion. Nevertheless, stimuli
      flashed briefly around the onset of a saccade are grossly mislocalized, resulting
      in a shift and, under certain conditions, an additional compression of visual
      space. Perisaccadic mislocalization has been related to a spatio-temporal
      misalignment of an extraretinal eye position signal with the corresponding
      saccade. Here, we investigated perceptual mislocalization of human observers both
      in saccade and fixation conditions. In the latter conditions, the retinal
      stimulation during saccadic eye movements was simulated by a fast saccade-like
      shift of the stimulus display. We show that the spatio-temporal pattern of both
      the shift and compression components of perceptual mislocalization can be
      surprisingly similar before real and simulated saccades. Our findings suggest
      that the full pattern of perisaccadic mislocalization can also occur in
      conditions which are unlikely to involve changes of an extraretinal eye position
      signal. Instead, we suggest that, under the conditions of our experiments, the
      arising difficulty to establish a stable percept of a briefly flashed stimulus
      within a given visual reference frame yields mislocalizations before fast retinal
      image motion. The availability of visual references appears to exert a major
      influence on the relative contributions of shift and compression components to
      mislocalization across the visual field.

PMID- 16289835
TI  - Analysis of transcriptional responses in the mouse dorsal striatum following
      acute 3,4-methylenedioxymethamphetamine (ecstasy): identification of
      extracellular signal-regulated kinase-controlled genes.
AB  - 3,4-Methylenedioxymethamphetamine (ecstasy), a widely used recreational drug with
      psychoactive properties, induces both serotonin and dopamine release in the
      brain. However, little is known about its intracellular effects. We previously
      showed that 3,4-methylenedioxymethamphetamine rewarding effects in mice were
      dependent upon extracellular signal-regulated kinase activation and that dorsal
      striatum was a critical region for mediating extracellular signal-regulated
      kinase-dependent Egr1 3,4-methylenedioxymethamphetamine-induced transcription.
      Here, we extend these findings by showing that 3,4-methylenedioxymethamphetamine
      is indeed able to activate extracellular signal-regulated kinase within this
      structure. To identify genes regulated by acute 3,4-methylenedioxymethamphetamine
      in the mice dorsal striatum, and selectively controlled by this kinase, we
      performed microarray experiments by using a selective inhibitor of extracellular
      signal-regulated kinase activation, SL327. Of the approximately 24,000 genes from
      the microarray, 27 showed altered expression after exposure to 3,4
      methylenedioxymethamphetamine, and among these, 59% were partially or totally
      inhibited by SL327 pretreatment. Our results showed that the genes regulated by
      3,4-methylenedioxymethamphetamine encode proteins that belong to transcription
      factors family, signaling pathways (phosphatases, cytoskeleton regulation), and
      synaptic functions. These early changes, and especially those controlled by
      extracellular signal-regulated kinase activation might play significant roles in
      the expression of many of the behaviors that occur following 3,4
      methylenedioxymethamphetamine taking.

PMID- 16289836
TI  - Oligodendrocytes exhibit selective expression of suppressor of cytokine signaling
      genes and signal transducer and activator of transcription 1 independent
      inhibition of interferon-gamma-induced toxicity in response to leukemia
      inhibitory factor.
AB  - Multiple sclerosis is an autoimmune disease of the CNS that results in the death
      of oligodendrocytes, the myelinating cells of the CNS. Previous studies have
      indicated that the cytokine leukemia inhibitory factor prevents the cytotoxic
      effects of interferon-gamma on oligodendrocytes in vitro, and the death of
      oligodendrocytes in an animal model of multiple sclerosis. Members of a recently
      characterized family of proteins, the suppressors of cytokine signaling, have
      been demonstrated to mediate negative cross-talk between cytokines, with
      induction of suppressors of cytokine signaling proteins by one cytokine
      inhibiting the activity of a second. Here, we assess whether induction of members
      of the suppressors of cytokine signaling family could explain the antagonistic
      biological effects of leukemia inhibitory factor and interferon-gamma upon
      oligodendrocytes. It is found that leukemia inhibitory factor rapidly and
      strongly induces the expression of suppressors of cytokine signaling-3 in
      cultured rat oligodendrocytes, whereas interferon-gamma weakly induces the
      expression of both suppressor of cytokine signaling-1 and 3. Pre-treatment of
      oligodendrocytes with leukemia inhibitory factor does not prevent the subsequent
      phosphorylation of signal transducer and activator of transcription-1 by
      interferon-gamma indicating that the leukemia inhibitory factor inhibition of
      interferon-gamma toxicity in oligodendrocytes is mediated by a suppressor of
      cytokine signaling-3 independent mechanism.

PMID- 16289837
TI  - Positional regulation of Pax2 expression pattern in mesencephalic and
      diencephalic alar plate.
AB  - Regionalization of the neural tube is a fundamental event in the development of
      the CNS. The isthmic organizer controls the development of the mesencephalic
      rhombencephalic junction by means of fibroblast growth factor 8 (Fgf8)
      expression. The transcription factor paired box 2 (Pax2) is expressed early in
      the midbrain and is later progressively restricted to the mid-hindbrain region,
      playing an important role in the development of the mesencephalon and the
      cerebellum. In this study, by implanting Fgf8-beads in the chick neural tube, we
      show that Fgf8 induces a heterogeneous pattern of Pax2 expression in the
      diencephalon. To explore the mechanisms controlling this asymmetric induction and
      the down-regulation of Pax2 in the anterior mesencephalon we performed antero
      posterior inversions of diencephalic and/or mesencephalic neuroepithelium, with
      or without Fgf8-bead implantation. We show that anterior factors do not play a
      role in Pax2 regionalization, while posterior factors could explain these
      expression patterns. We conclude that the anterior mesencephalon and the
      diencephalon are able to retain or activate Pax2 expression under caudal
      influences, and to develop as a tectal structure at later developmental stages.

PMID- 16289838
TI  - Minocycline alleviates hypoxic-ischemic injury to developing oligodendrocytes in
      the neonatal rat brain.
AB  - The role of minocycline in preventing white matter injury, in particular the
      injury to developing oligodendrocytes was examined in a neonatal rat model of
      hypoxia-ischemia. Hypoxia-ischemia was achieved through bilateral carotid artery
      occlusion followed by exposure to hypoxia (8% oxygen) for 15 min in postnatal day
      4 Sprague-Dawley rats. A sham operation was performed in control rats.
      Minocycline (45 mg/kg) or normal phosphate-buffered saline was administered
      intraperitoneally 12 h before and immediately after bilateral carotid artery
      occlusion+hypoxia and then every 24 h for 3 days. Nissl staining revealed
      pyknotic cells in the white matter area of the rat brain 1 and 5 days after
      hypoxia-ischemia. Hypoxia-ischemia insult also resulted in apoptotic
      oligodendrocyte cell death, loss of O4+ and O1+ oligodendrocyte immunoreactivity,
      and hypomyelination as indicated by decreased myelin basic protein immunostaining
      and by loss of mature oligodendrocytes in the rat brain. Minocycline
      significantly attenuated hypoxia-ischemia-induced brain injury. The protective
      effect of minocycline was associated with suppression of hypoxia-ischemia-induced
      microglial activation as indicated by the decreased number of activated
      microglia, which were also interleukin-1beta and inducible nitric oxide synthase
      expressing cells. The protective effect of minocycline was also linked with
      reduction in hypoxia-ischemia-induced oxidative and nitrosative stress as
      indicated by 4-hydroxynonenal and nitrotyrosine positive oligodendrocytes,
      respectively. The reduction in hypoxia-ischemia-induced oxidative stress was also
      evidenced by the decreases in the content of 8-isoprostane in the minocycline
      treated hypoxia-ischemia rat brain as compared with that in the vehicle-treated
      hypoxia-ischemia rat brain. The overall results suggest that reduction in
      microglial activation may protect developing oligodendrocytes in the neonatal
      brain from hypoxia-ischemia injury.

PMID- 16289840
TI  - 11beta-Hydroxysteroid dehydrogenase type 2 protects the neonatal cerebellum from
      deleterious effects of glucocorticoids.
AB  - 11beta-Hydroxysteroid dehydrogenase type 2 is a glucocorticoid metabolizing
      enzyme that catalyzes rapid inactivation of corticosterone and cortisol to inert
      11-keto derivatives. As 11beta-hydroxysteroid dehydrogenase type 2 is highly
      expressed in the developing brain, but not in the adult CNS, we hypothesized that
      it may represent a protective barrier to the deleterious actions of
      corticosteroids on proliferating cells. To test this hypothesis we have
      investigated the development and growth of the cerebellum in neonatal C57BL/6
      mice and mice lacking 11beta-hydroxysteroid dehydrogenase type 2 (-/-). 11beta
      Hydroxysteroid dehydrogenase type 2-/- mice had consistently lower body weight
      throughout the neonatal period, coupled with a smaller brain size although this
      was normalized when corrected for body weight. The cerebellar size was smaller in
      11beta-hydroxysteroid dehydrogenase type 2-/- mice, due to decreases in size of
      both the molecular and internal granule layers. When exogenous corticosterone was
      administered to the pups between postnatal days 4 and 13, 11beta-hydroxysteroid
      dehydrogenase type 2(-/-) mice were more sensitive, showing further inhibition of
      cerebellar growth while the wildtype mice were not affected. Upon withdrawal of
      exogenous steroid, there was a rebound growth spurt so that at day 21
      postnatally, the cerebellar size in 11beta-hydroxysteroid dehydrogenase type 2-/-
      mice was similar to untreated mice of the same genotype. Furthermore, 11beta
      hydroxysteroid dehydrogenase type 2-/- mice had a delay in the attainment of
      neurodevelopmental landmarks such as negative geotaxis and eye opening. We
      therefore suggest that 11beta-hydroxysteroid dehydrogenase type 2 acts as to
      protect the developing nervous system from the deleterious consequences of
      glucocorticoid overexposure.

PMID- 16289839
TI  - Inhibition of mechanosensitivity in visceral primary afferents by GABAB receptors
      involves calcium and potassium channels.
AB  - GABA(B) receptors inhibit mechanosensitivity of visceral afferents. This is
      associated with reduced triggering of events that lead to gastro-esophageal
      reflux, with important therapeutic consequences. In other neuronal systems,
      GABA(B) receptor activation may be linked via G-proteins to reduced N-type Ca(2+)
      channel opening, increased inward rectifier K(+) channel opening, plus effects on
      a number of intracellular messengers. Here we aimed to determine the role of
      Ca(2+) and K(+) channels in the inhibition of vagal afferent mechanoreceptor
      function by the GABA(B) receptor agonist baclofen. The responses of three types
      of ferret gastro-esophageal vagal afferents (mucosal, tension and tension mucosal
      receptors) to graded mechanical stimuli were investigated in vitro. The effects
      of baclofen (200 microM) alone on these responses were quantified, and the
      effects of baclofen in the presence of the G-protein-coupled inward rectifier
      potassium channel blocker Rb(+) (4.7 mM) and/or the N-type calcium channel
      blocker omega-conotoxin GVIA (0.1 microM). Baclofen inhibition of mucosal
      receptor mechanosensitivity was abolished by both blockers. Its inhibitory effect
      on tension mucosal receptors was partly reduced by both. The inhibitory effect of
      baclofen on tension receptors was unaffected. The data indicate that the
      inhibitory action of GABA(B) receptors is mediated via different pathways in
      mucosal, tension and tension mucosal receptors via mechanisms involving both N
      type Ca(2+) channels and inwardly rectifying K(+) channels and others.

PMID- 16289841
TI  - Fictive locomotor patterns generated by tetraethylammonium application to the
      neonatal rat spinal cord in vitro.
AB  - Intrinsic spinal networks generate a locomotor rhythm characterized by
      alternating electrical discharges from flexor and extensor motor pools. Because
      this process is preserved in the rat isolated spinal cord, this preparation in
      vitro may be a useful model to explore methods to reactivate locomotor networks
      damaged by spinal injury. The present electrophysiological investigation examined
      whether the broad spectrum potassium channel blocker tetraethylammonium could
      generate locomotor-like patterns. Low (50-500 microM) concentrations of
      tetraethylammonium induced irregular, synchronous discharges incompatible with
      locomotion. Higher concentrations (1-10 mM) evoked alternating discharges between
      flexor and extensor motor pools, plus large depolarization of motoneurons with
      spike broadening. The alternating discharges were superimposed on slow, shallow
      waves of synchronous depolarization. Rhythmic alternating patterns were
      suppressed by blockers of glutamate, GABA(A) and glycine receptors, disclosing a
      background of depolarizing bursts inhibited by antagonism of group I metabotropic
      glutamate receptors. Furthermore, tetraethylammonium also evoked irregular
      discharges on dorsal roots. Rhythmic alternating patterns elicited by
      tetraethylammonium on ventral roots were relatively stereotypic, had limited
      synergy with fictive locomotion induced by dorsal root stimuli, and were not
      accelerated by 4-aminopyridine. Horizontal section of the spinal cord preserved
      irregular ventral root discharges and dorsal root discharges, demonstrating that
      the action of tetraethylammonium on spinal networks was fundamentally different
      from that of 4-aminopyridine. These results show that a potassium channel blocker
      such as tetraethylammonium could activate fictive locomotion in the rat isolated
      spinal cord, although the pattern quality lacked certain features like frequency
      modulation and strong synergy with other inputs to locomotor networks.

PMID- 16289842
TI  - Cellular distribution of D-serine, serine racemase and D-amino acid oxidase in
      the rat vestibular sensory epithelia.
AB  - Glutamate is the main neurotransmitter at the synapses between sensory cells and
      primary afferents in the peripheral vestibular system. Evidence has recently been
      obtained demonstrating that the atypical amino acid D-serine is the main
      endogenous co-agonist of the N-methyl-D-aspartate receptors in the CNS. We
      studied the distribution of D-serine and its synthesizing and degrading enzymes,
      serine racemase and d-amino acid oxidase in the rat vestibular sensory epithelium
      using immunocytochemistry. D-serine, serine racemase and D-amino acid oxidase
      were localized in the transitional cells, which are parasensory cells located
      between the sensory epithelium and the dark cells. The dark cells expressed only
      serine racemase. D-Serine was also detected in the supporting cells of the
      sensory epithelium. These cells, which are in close contact with glutamatergic
      synapses, express GLAST, a glial specific transporter for glutamate. They may
      have similar functions to glial cells in the CNS and thus expression of D-serine
      suggests a neuromodulator role for D-serine at the glutamatergic synapses in the
      peripheral vestibular system. Our data also indicate that the metabolism of D
      serine is not restricted to glial cells suggesting that the amino acid may play
      an additional role in the peripheral nervous system.

PMID- 16289843
TI  - Immunohistochemical evidence of functional leptin receptor expression in neuronal
      and endothelial cells of the rat brain.
AB  - Leptin binding to its functional receptor leads to activation of the JAK-STAT
      signaling pathway and especially to the activation of the signal transducer and
      activator of transcription factor 3 (STAT3). The immunohistochemical detection of
      nuclear STAT3 translocation is used as a neuroanatomical mapping tool to
      determine leptin-responsive cells in the rat brain. This study neuroanatomically
      identifies those brain cell phenotypes showing STAT3 activation after
      intraperitoneal leptin treatment (5 mg/kg) using immunohistochemical
      colocalization with neuronal and endothelial cell marker proteins. Leptin
      treatment induced nuclear STAT3 signals with the strongest response observed
      90min after the treatment. The caudobasal hypothalamus showed a particularly
      pronounced STAT3 response. Leptin-induced nuclear STAT3 signals were additionally
      determined in the solitary tract nucleus, the choroid plexus and in the brain
      endothelium. The vast majority of STAT3-responsive cells proved to be neurons
      located in the caudobasal hypothalamus, however, a marked number of brain
      endothelial cells distributed throughout the entire brain got activated as well.
      In conclusion, neurons and non-neuronal brain cells, e.g., endothelial or choroid
      plexus cells, seem to express functional leptin receptors and might thereby
      mediate leptin-dependent functions in the rat brain.

PMID- 16289844
TI  - Membrane voltage differently affects mIPSCs and current responses recorded from
      somatic excised patches in rat hippocampal cultures.
AB  - Recent analysis of current responses to exogenous GABA applications recorded from
      excised patches indicated that membrane voltage affected the GABAA receptor
      gating mainly by altering desensitization and binding [M. Pytel, K. Mercik, J.W.
      Mozrzymas, Membrane voltage modulates the GABAA receptor gating in cultured rat
      hippocampal neurons, Neuropharmacology, in press]. In order investigate the
      impact of such voltage effect on GABAA receptors in conditions of synaptic
      transmission, mIPSCs and current responses to rapid GABA applications were
      recorded from the same culture of rat hippocampal neurons. We found that I-V
      relationship for mIPSCs amplitudes showed a clear outward rectification while for
      current responses an inward rectification was seen, except for very low GABA
      concentrations. A clear shift in amplitude cumulative distributions indicated
      that outward rectification resulted from the voltage effect on the majority of
      mIPSCs. Moreover, the decaying phase of mIPSCs was clearly slowed down at
      positive voltages and this effect was represented by a shift in cumulative
      distributions of weighted decaying time constants. In contrast, deactivation of
      current responses was only slightly affected by membrane depolarization. These
      data indicate that the mechanisms whereby the membrane voltage modulates synaptic
      and extrasynaptic receptors are qualitatively different but the mechanism
      underlying this difference is not clear.

PMID- 16289845
TI  - No association of two common SNPs at position -1727 A/T, -50 C/T of GSK-3 beta
      polymorphisms with schizophrenia and bipolar disorder of Korean population.
AB  - Recent studies have suggested the involvement of Glycogen synthase kinase-3 beta
      (GSK-3 beta) in pathogenesis and treatment target of schizophrenia and bipolar
      disorder, which led to consider GSK-3 beta as one of the candidate genes for
      those disorders. However, the association analysis between GSK-3 beta and either
      schizophrenia or bipolar disorder is yet to be reported in Korean population.
      Along with 350 healthy individuals, a sample of 138 schizophrenia and 120 bipolar
      patients was analyzed for two common SNPs at position -1727 A/T and -50 C/T
      polymorphism localized in intron 1 of the gene. The results showed that allele,
      genotype and haplotype distributions for the two SNPs do not differ between the
      controls and neither schizophrenia nor bipolar disorder patients. We also
      analyzed the association between the controls and the combined samples of
      schizophrenia and bipolar disorder, but no association was found. In conclusion,
      these results suggest that the GSK-3 beta is not associated with the development
      of schizophrenia and bipolar disorder in Korean population.

PMID- 16289846
TI  - Review of forensic assessments of female referrals to the branch of legal
      medicine, Malatya region, Turkey--1996-2000.
AB  - It is well recognized that the most pervasive form in gender violence is violence
      against women by their intimate male partners. Domestic violence (DV) crosses all
      cultures, races, and socioeconomic levels, affecting people of all ages and both
      sexes, but particularly women and children. DV refers to the chronic physical,
      sexual and psychological maltreatment of one family member against another in
      order to control. DV represents a significant health threat to women. It may also
      be an important precipitating factor of female suicide. As the literature has
      begun to document the extent of interfamilial violence, attention has focused on
      forensic documentation. The aim of this study is to review female victims
      presented at the Branch of Legal Medicine of Malatya, Turkey, regarding gender
      based violence and DV in relation towards sexual offenses and suicide attempts.
      Accordingly, recommendations were presented to increase the awareness of DV by
      setting policies and in response legislative recommendations. The legal reports
      of women (n=2245) were reviewed. In respect of the Turkish Penal Code (TPC),
      paragraph 456/1, 2, 3 and 4, which covers the act of assault and battery, the
      severity of the injuries have been categorized into three groups according to the
      Turkish Injury Scale (TIS) covered by TPC 456/1, 2 and 4, into the issues of
      functional incapacitation according to TPC 456/2 and 3, and with regard to the
      presence of a mark of an injury on the face according to TPC 456/2 tables.
      Because of incomplete data, not all results be categorized as positive for DV.
      Despite the large number of blunt force injuries (699 cases out of 2245) and the
      high percentage of external lesions, 76% of 1796 files, found, recognition of DV
      was uncommon. According to TPC 456/4, in cases of small trauma-related injuries,
      legal proceedings are dependent upon a victim's making a complaint. The
      percentage of 80.4% (n=2245) represents the need for information regarding legal
      requirements. The frequency of sexual assault cases, 144 victims out of 162, and
      in suicide attempts, 95 women out of 145, in the 15-24 year age span may also
      reflect a society's accusative approach towards women based on moral values.
      Unless prosecuting DV cases purely on the evidence in regard to victim's safety,
      withdrawal of complaints will continue. It is essential to identify to 'name' DV
      when it occurs. Recognizing the serious immediate and future long-term
      implications for health, multifaceted intervention is important. DV has to
      undergo some fundamental and far-reaching reformation in Turkey regarding how the
      legal system deals with it appropriately.

PMID- 16289847
TI  - Membrane recruitment of effector proteins by Arf and Rab GTPases.
AB  - In their GTP-bound form, Arf and Rab family GTPases associate with distinct
      organelle membranes, to which they recruit specific sets of effector proteins
      that regulate vesicular transport. The Arf GTPases are involved in the formation
      of coated carrier vesicles by recruiting coat proteins. On the other hand, the
      Rab GTPases are involved in the tethering, docking and fusion of transport
      vesicles with target organelles, acting in concert with the tethering and fusion
      machineries. Recent structural studies of the Arf1-GGA and Rab5-Rabaptin-5
      complexes, as well as other effector structures in complex with the Arf and Rab
      GTPases, have shed light on the mechanisms underlying the GTP-dependent membrane
      recruitment of these effector proteins.

PMID- 16289848
TI  - The structure and regulation of myotubularin phosphatases.
AB  - The human neuromuscular diseases X-linked myotubular myopathy and Charcot-Marie
      Tooth disease type 4B are caused by mutations in myotubularin family proteins.
      The myotubularins are a unique subfamily of protein tyrosine phosphatases that
      utilize inositol phospholipids, rather than phosphoproteins, as substrates.
      Recent structural studies, including the first crystal structure of a
      myotubularin family protein, have defined the structural features that are
      characteristic of the family and revealed the molecular basis of their unique
      substrate specificity. Interestingly, the myotubularin family contains a subgroup
      of proteins that are catalytically inactive. Recent biochemical studies have
      established that the inactive myotubularins function as adaptors for the active
      members and play an important regulatory role within the family.

PMID- 16289849
TI  - Enteral nutrition in intensive care nurses' perceptions and bedside observations.
AB  - The aims of this descriptive study were to examine (1) nurses' perceptions of
      responsibility, knowledge and documentation focusing on enteral nutrition and (2)
      nursing practice regarding enteral feeding in the intensive care unit. Forty-four
      nurses in three intensive care units responded to a questionnaire (response rate
      70%) and 40 bedside observations were performed. The nurses' primary source of
      knowledge was consultation with colleagues. Regarding responsibility, knowledge
      and documentation, the focus was more on planning, implementation and prevention
      than on the assessing phase of the nursing process. Gastric residual volumes were
      almost never checked, and none of the tubes were labelled. Seven out of 40
      bedside observations revealed a backrest elevation of 30 degrees or more. Mean
      backrest elevation was 20.7 degrees. Comparisons between nurses in the three
      hospitals revealed significant differences. This study indicates that enteral
      nutritional nursing care within intensive care has its strength in planning,
      implementation and prevention of complications. Regarding nutritional assessment,
      the registered nurses (RNs) scored low. There are gaps between recommended
      nursing care and nursing practice regarding enteral nutrition. Knowledge and
      awareness of responsibilities in combination with a systematic documentation
      could increase the optimal nutritional care of the intensive care patient.

PMID- 16289850
TI  - Inhibition of intestinal and renal Na+-glucose cotransporter by naringenin.
AB  - Reduction in glucose uptake constitutes a possible means of controlling diabetic
      hyperglycemia. Using purified intestinal brush border membrane vesicles and
      everted intestinal sleeves, we have demonstrated that naringenin, a flavonoid
      present in citrus fruits and juices, significantly inhibited glucose uptake in
      the intestine. In addition, naringenin also elicited inhibitory actions towards
      glucose uptake in renal brush border membrane vesicles. Naringin, a glycoside of
      naringenin, was totally inactive in these aspects. Naringenin exhibited moderate
      inhibitory action on glucose uptake in rabbit intestinal brush border membrane
      vesicles, and showed strong inhibitory action in rat everted intestinal sleeves.
      The IC(50) values were 205.9 and 2.4 micromol/l, respectively. Lineweaver-Burk
      analysis demonstrated that naringenin inhibited glucose uptake in rat everted
      intestinal sleeves in a competitive manner with a K(i) value of 1.1 micromol/l.
      Glucose uptake activities in both the intestinal and renal brush border membrane
      vesicles of diabetic rats were significantly higher than in normal rats.
      Naringenin (500 microM) reduced glucose uptake by more than 60% in both the
      intestinal and renal brush border membrane vesicles of diabetic rats to a level
      similar to that of the normal rats. The IC(50) values of naringenin in the renal
      brush border membrane vesicles of normal and diabetic rats were 323.9 and 166.1
      micromol/l, respectively. These results suggest that inhibition of intestinal
      glucose uptake and renal glucose reabsorption explains, in part at least, the in
      vivo antihyperglycemic action of naringenin and its derivatives. The possible
      application of these natural compounds in controlling hyperglycemia warrants
      further investigations.

PMID- 16289852
TI  - Automated magnification calibration in transmission electron microscopy using
      Fourier analysis of replica images.
AB  - The magnification factor in transmission electron microscopy is not very precise,
      hampering for instance quantitative analysis of specimens. Calibration of the
      magnification is usually performed interactively using replica specimens,
      containing line or grating patterns with known spacing. In the present study, a
      procedure is described for automated magnification calibration using digital
      images of a line replica. This procedure is based on analysis of the power
      spectrum of Fourier transformed replica images, and is compared to interactive
      measurement in the same images. Images were used with magnification ranging from
      1,000 x to 200,000 x. The automated procedure deviated on average 0.10% from
      interactive measurements. Especially for catalase replicas, the coefficient of
      variation of automated measurement was considerably smaller (average 0.28%)
      compared to that of interactive measurement (average 3.5%). In conclusion,
      calibration of the magnification in digital images from transmission electron
      microscopy may be performed automatically, using the procedure presented here,
      with high precision and accuracy.

PMID- 16289851
TI  - Making sense of antisense.
AB  - The specific and rational targeting of key genes, identified to be vital to
      driving cancer growth, has recently led to the successful development of several
      small molecule and antibody therapeutics. However, despite considerable efforts,
      antisense oligonucleotides (ASO) have yet to prove their worth as targeted
      therapies. However, many important genes cannot be readily targeted by antibodies
      or small molecules, and could be blocked by ASOs. Moreover, the latest generation
      of ASOs is safe, well tolerated and able to modulate target protein expression
      both in surrogate and tumour tissue in the clinic. This review will describe the
      experience acquired with these agents to date and will raise critical issues
      relevant to the further optimal development of these agents. Future clinical
      studies need to evaluate combinations of several different ASO targeting multiple
      key targets, including strategies that reverse functional redundancy of the key
      target (e.g., targeting several Bcl family members including Bcl-2 and Bcl-x).
      Approaches to maximise the duration of target blockade yet avert the need for
      prolonged intravenous infusions, with the consequent risk of line infection and
      thrombosis, are also needed. These may include slow-release depot subcutaneous
      formulations. Short interfering (Si) RNA therapeutics, which are now being
      evaluated in early clinical trials, are also envisioned to impact the future
      utility of this class of therapeutics. The high manufacture cost of these agents,
      when compared with small chemical molecules, could however, limit their success
      unless cost-effective manufacturing processes are developed.

PMID- 16289853
TI  - Combination of porphyrins and DNA-alkylation agents: synthesis and tumor cell
      apoptosis induction.
AB  - A series of porphyrin-DNA cross-linking conjugates were synthesized. Their
      cytotoxicities to tumor cells were tested using MTT assays first. Then, HeLa cell
      apoptosis induced by these cationic porphyrins under the light was examined by
      laser confocal microscopy, flow cytometric analysis, and further confirmed by
      observing the morphological changes and DNA fragmentation mainly.

PMID- 16289854
TI  - 99mTc-labeling of colchicine using [99mTc(CO)3(H2O)3]+ and [99mTc triple bond
      N]2+ core for the preparation of potential tumor-targeting agents.
AB  - Multidrug resistance (MDR) mediated by over-expression of P-glycoprotein (Pgp) is
      one of the major causes of failure of chemotherapy in cancer treatment.
      Colchicine, a naturally occurring alkaloid, is a Pgp substrate and acts as an
      antimitotic agent by binding to microtubules. Hence, Colchicine and its analogues
      radiolabeled with 99mTc may have potential for visualization of MDR in tumors.
      Here we report 99mTc-labeling of colchicine derivatives using [99mTc(CO)3(H2O)3]+
      and [99mTc triple bond N]2+ cores. Trimethylcolchicinic acid synthesized from
      colchicine was used as the precursor to prepare iminodiacetic acid and
      dithiocarbamate derivatives which were then radiolabeled with [99mTc(CO)3(H2O)3]+
      and [99mTc triple bond N]2+ cores, respectively. Radiolabeling yield for both the
      complexes was > 98% as observed by HPLC and TLC patterns. In vitro studies in
      tumor cell lines showed significant uptake for 99mTc-carbonyl as well as for
      99mTc-nitrido colchicine complexes. Biodistribution studies in Swiss mice bearing
      fibrosarcoma tumor showed 4.1 +/- 1.2% ID/g of uptake at 30 min pi for 99mTc(CO)3
      complex as against 0.42 +/- 0.24% ID/g for the 99mTcN-complex. 99mTc(CO)3
      colchicine complex exhibited better pharmacokinetics with lower liver
      accumulation as compared to the 99mTcN-complex. Thus, colchicine radiolabeled
      with [99mTc(CO)3(H2O)3]+ core is more promising with respect to in vivo
      distribution characteristics in tumor model.

PMID- 16289855
TI  - Novel tricyclic quinazolinimines and related tetracyclic nitrogen bridgehead
      compounds as cholinesterase inhibitors with selectivity towards
      butyrylcholinesterase.
AB  - Tetracyclic nitrogen bridgehead compounds, dibenzodiazecines and tricyclic
      quinazolinimines, in which the size of the alicyclic ring system and the length
      of the alkyl chain between the quinazolinimine moiety and a phenyl ring connected
      to the imine nitrogen atom were changed systematically, were synthesized and
      their ability to inhibit acetyl- and butyrylcholinesterase (AChE/BChE),
      respectively, was evaluated. Moderate and strong inhibitors of BChE--compared to
      galanthamine and rivastigmine--were identified, which show mixed affinities or
      are moderately or highly selective towards BChE, respectively.

PMID- 16289856
TI  - Synthesis, in vitro pharmacology and biodistribution studies of new PD 156707
      derived ET(A) receptor radioligands.
AB  - It is assumed that the regulation of cardiac endothelin (ET) receptor density is
      abnormal in heart diseases. From that perspective, an ET receptor radioligand is
      needed to assess ET receptor density in vivo. The nonpeptidyl ET(A) receptor
      antagonist PD 169390 was labelled with radioiodine to give a putative radioligand
      for SPECT. Labelling with [125I]iodide and [123I]iodide was accomplished with
      good to excellent radiochemical yields. The affinities of the nonradioactive
      reference and those of selected precursor compounds for ET(A) receptors were
      determined, using [125I]iodine labelled endothelin-1 with mouse ventricular
      membranes. All employed substances exhibited potent in vitro pharmacological
      characteristics with Ki values comparable to that of the lead compound PD 156707.
      Biodistribution studies and scintigraphic imaging experiments in mice, however,
      showed no significant uptake of the [123I] derivative in the heart.

PMID- 16289857
TI  - Structure-activity relationship study of homoallylamines and related derivatives
      acting as antifungal agents.
AB  - The synthesis, in vitro evaluation, and structure-activity relationship studies
      of homoallylamines and related derivatives acting as antifungal agents are
      reported. Among them, compounds N-(4-bromophenyl)-N-(2-furylmethyl)amine and N-(4
      chlorophenyl)-N-(2-furylmethyl)amine reported here exhibited remarkable
      antifungal activity against dermatophytes. Theoretical calculations allow us to
      determine the minimal structural requirements to produce the antifungal response
      and can provide a guide for the design of compounds with these properties.

PMID- 16289858
TI  - Structural characteristics of novel symmetrical diaryl derivatives with
      nitrogenated functions. Requirements for cytotoxic activity.
AB  - In an attempt to discover the essential features that would allow us to explain
      the differences in cytotoxic activity shown by a series of symmetrical diaryl
      derivatives with nitrogenated functions, we have studied by molecular modelling
      techniques the variation in Log P and conformational behaviour, in terms of
      structural modifications. The Log P data--although they provide few clues
      concerning the observed variability in activity--suggest that an initial
      separation of active and inactive compounds is possible based on this parameter.
      The subsequent study of the conformational behaviour of the compounds, selected
      according to their Log P values, showed that the active compounds preferentially
      display an extended conformation and inactive ones are associated with a certain
      type of folding, with a triangular-type conformation adopted in these cases.

PMID- 16289859
TI  - Association of a D2S2944 allele with depression specifically among those with
      substance abuse or antisocial personality.
AB  - Associations have previously been reported between a 124-bp allele at D2S2944 and
      recurrent, early-onset depression in women. These earlier reports also noted but
      did not emphasize a possible association between this allele and alcohol-specific
      depression. We have analyzed the Iowa Adoption Study data to test this
      association. D2S2944 allele typing was available for 247 subjects from the Iowa
      Adoption Studies. Information on lifetime affective, alcohol, drug, and
      antisocial personality (ASPD) disorders was available from a structured
      interview. We used logistic regression to analyze adjusted and interactive
      D2S2944 associations with depression. Controlling other risk factors, the 124-bp
      allele had a strong association with DSM-IV major depression specific to those
      with histories of alcohol abuse/dependence and/or ASPD. (Overlap between the two
      prevented further specification of the interaction.) The association was not
      gender-specific and was not limited to alcohol-related depressive episodes. This
      relationship appears stronger than the D2S2944 association previously reported
      for early-onset depression in women. We note that, in combination with additional
      liabilities towards depression in women and alcoholism/sociopathy in men, the 124
      bp allele may provide a basis for the phenomenon of depressive spectrum illness
      proposed by Winokur.

PMID- 16289860
TI  - TGF-beta and cancer.
AB  - TGF-beta signaling regulates tumorigenesis and in human cancer its signaling
      pathways are often modified during tumor progression. Prior to initiation and
      early during progression TGF-beta acts upon the epithelium as a tumor suppressor,
      however at later stages it is often a tumor promoter. Over the years, many
      studies have focused on the epithelial cell autonomous role for TGF-beta,
      however, TGF-beta is not strictly limited to this compartment in vivo. Recent
      studies addressing TGF-beta mediated stromal-epithelial interactions have
      significantly improved our understanding related to the regulation of cancer. In
      addition, stromal fibroblast cell autonomous effects have been observed in
      response to TGF-beta stimulation. According to the current literature and
      experimental evidence, TGF-beta is a potent ligand that regulates carcinoma
      initiation, progression and metastasis through a broad and complex spectrum of
      interdependent interactions.

PMID- 16289861
TI  - Seroepidemiology of Neospora caninum infection in dairy cattle herds in Mashhad
      area, Iran.
AB  - A seroepidemiology study of Neospora caninum was conducted in Mashhad area,
      Khorasan province, Iran on 337 cattle from 30 dairy using ELISA. All herds had
      seropositive cattle and antibodies were formed in 46% of the cattle. Abortion was
      significantly associated with seropositivity of cattle. The highest risk of
      abortion was observed in the 1-2-year-old cows. Our results indicate that
      Neospora infection is widespread in Iran.

PMID- 16289862
TI  - Field trial on comparative efficacy of four fasciolicides against natural liver
      fluke infection in cattle.
AB  - A controlled trial was conducted to evaluate the current efficacy of albendazole
      (ABZ), rafoxanide (RFX), triclabendazole (TRC) or clorsulon (CLS) against
      Fasciola hepatica in naturally infected cattle. This trial was conducted in
      Turkey during the spring, the time of year when liver fluke infection is endemic.
      Fifty crossbred cattle were selected for inclusion in the trial based on finding
      eggs of F. hepatica in the feces. The cattle were weighed and randomly allotted
      into five groups of 10 cattle and treatments were as follows: Group 1 served as
      non-treated control (CONT), Group 2 was treated orally with ABZ at 12 mg/kg,
      Group 3 was treated orally with RFX at 10 mg/kg, Group 4 received TRC orally at
      12 mg/kg and Group 5 received CLS administered subcutaneously (s.c.) at 2 mg/kg.
      On day 0 (inclusion day), individual fecal samples were collected on days 0
      (inclusion day), 7, 14, 28 and 56, after treatment. The drug efficacy was
      assessed as a percentage of the egg or fluke reduction and body weight gain
      relative to the untreated control. The results in the study showed a mean
      reduction of egg counts by 66.7%, 68.2%, 78% and 84.2% in Groups 2-5,
      respectively. In conclusion, our results indicate that CLS is a highly effective
      compound for the treatment of F. hepatica in cattle under these field conditions.

PMID- 16289863
TI  - Investigation of Neospora sp. and Toxoplasma gondii antibodies in mares and in
      precolostral foals from Parana State, Southern Brazil.
AB  - Antibodies to Neospora sp. and Toxoplasma gondii were measured in mares and
      precolostral foals from a farm in Parana State, Brazil. An indirect fluorescent
      antibody test (IFAT) was used to determine specific antibodies. Three sampling
      points, 2003, 2004 and at parturition were included in the study, but not all
      horses are represented at a parturition time point. In 2003, antibodies to
      Neospora were detected in 17 mares (47%) at 1:50 dilution and in 5 mares (13.8%)
      at 1:100 dilution. In 2004, antibodies to Neospora were found in 11/36 (30%)
      horses with titers of 1:50 and in 6 mares (16.6%) at 1:100 dilution. The
      prevalence of antibodies against T. gondii was 2.7% in mares, either in 2003 and
      2004. Evidence for the role of Neospora sp. in equine reproduction failure was
      not observed in the farm. Immunoglobulin G antibodies to Neospora were found in
      two of the nine precolostrum foals. Four seronegative foals were born from
      seronegative mothers, and three seronegative foals were born from seropositive
      mothers (1:50). Two seropositive precolostrum foals were born from seropositive
      mothers (1:50). The foals were born clinically normal, and T. gondii antibodies
      were not detected in their serum samples. The total immunoglobulins values
      detected on seronegative precolostrum foals were lower than the levels observed
      in the seropositive foals. This data warrants additional studies to differentiate
      N. hughesi and N. caninum serologically and determination if these parasites were
      associated with equine neurological disease and reproductive failure.

PMID- 16289864
TI  - The c-Yes 3'-UTR contains adenine/uridine-rich elements that bind AUF1 and HuR
      involved in mRNA decay in breast cancer cells.
AB  - c-Yes is a member of the c-Src family of tyrosine kinases and has been implicated
      in intracellular signaling, cell morphology, and adhesion. Changes in its
      expression have also been associated with the aggressiveness of human breast and
      colon cancer cells. In MDA-MB-231 human breast cancer cells, overexpression of
      the small heat shock protein 27 (hsp27) results in a downregulation of c-Yes
      levels, concomitant with increased in vitro invasiveness and in vivo metastatic
      behavior. Very little is known, however, about the mechanisms regulating c-Yes
      expression. Here, we demonstrate that hsp27-induced c-Yes downregulation is not
      due to a reduction in transcriptional activity. However, the 3'-untranslated
      region (3'-UTR) of the c-Yes gene may be involved in its own regulation, since
      this region affects heterologous reporter gene activity in transactivation
      assays. This down-regulatory effect maps to three adenine/uridine-rich elements
      (AREs) that bind to cellular HuR and AUF1 (hnRNP D), two ARE-binding proteins
      (ARE-BPs) implicated in accelerated mRNA degradation. Our results suggest that
      the c-Yes 3'-UTR contains at least three newly identified AREs which are bound
      specifically by ARE-BPs, and provide a structural basis for post-transcriptional
      regulation of c-Yes expression.

PMID- 16289865
TI  - Acute toxicological effects of copper nanoparticles in vivo.
AB  - To assess the toxicity of copper nanoparticles (23.5 nm) in vivo, LD(50),
      morphological changes, pathological examinations and blood biochemical indexes of
      experimental mice are studied comparatively with micro-copper particles (17
      microm) and cupric ions (CuCl(2).2H(2)O). The LD(50) for the nano-, micro-copper
      particles and cupric ions exposed to mice via oral gavage are 413, >5000 and 110
      mg/kg body weight, respectively. The toxicity classes of nano and ionic copper
      particles both are class 3 (moderately toxic), and micro-copper is class 5
      (practically non-toxic) of Hodge and Sterner Scale. Kidney, liver and spleen are
      found to be target organs of nano-copper particles. Nanoparticles induce gravely
      toxicological effects and heavy injuries on kidney, liver and spleen of
      experimental mice, but micro-copper particles do not, on mass basis. Results
      indicate a gender dependent feature of nanotoxicity. Several factors such as huge
      specific surface area, ultrahigh reactivity, exceeding consumption of H(+), etc.
      that likely cause the grave nanotoxicity observed in vivo are discussed.

PMID- 16289866
TI  - Progressive neuronal loss and behavioral impairments of transgenic C57BL/6 inbred
      mice expressing the carboxy terminus of amyloid precursor protein.
AB  - The beta-secretase cleaved Abeta-bearing carboxy-terminal fragments (betaCTFs) of
      amyloid precursor protein (APP) in neural cells have been suggested to be
      cytotoxic. However, the functional significance of betaCTFs in vivo remains
      elusive. We created a transgenic mouse line Tg-betaCTF99/B6 expressing the human
      betaCTF99 in the brain of inbred C57BL/6 strain. Tg-betaCTF99/B6 mouse brain at
      12-16 months showed severely down-regulated calbindin, phospho-CREB, and Bcl-xL
      expression and up-regulated phospho-JNK, Bcl-2, and Bax expression. Neuronal cell
      density in the Tg-betaCTF99/B6 cerebral cortex at 16-18 months was lower than
      that of the non-transgenic control, but not at 5 months. At 11-14 months, Tg
      betaCTF99/B6 mice displayed cognitive impairments and increased anxiety, which
      were not observed at 5 months. These results suggest that increased betaCTF99
      expression is highly detrimental to the aging brain and that it produces a
      progressive and age-dependent AD-like pathogenesis.

PMID- 16289867
TI  - Additive neuroprotective effects of a histone deacetylase inhibitor and a
      catalytic antioxidant in a transgenic mouse model of amyotrophic lateral
      sclerosis.
AB  - ALS is a devastating neurodegenerative disorder for which no effective treatment
      exists. Multiple molecular mechanisms are involved in the pathogenesis. We tested
      the catalytic antioxidant AEOL 10150, the histone deacetylase inhibitor
      phenylbutyrate (PBA), and the combination of PBA and AEOL 10150 in the G93A
      transgenic mouse model, administered from disease onset. AEOL 10150 alone
      improved motor function and extended survival by 11%, PBA alone significantly
      improved motor function and extended survival by 13%. PBA and AEOL 10150 together
      increased survival by 19%. Increased histone acetylation was confirmed by Western
      blot. Quantitative real-time RT-PCR analysis revealed upregulation of compounds
      capable of protecting cells against oxidative stress and apoptosis. Markers of
      oxidative damage were reduced in the lumbar spinal cord as compared to vehicle
      administration. These results suggest that agents inhibiting apoptosis and
      blocking oxidative stress show efficacy in treating mutant-SOD1-associated ALS
      and that a combination of agents targeting different disease mechanisms may exert
      additive therapeutic effects.

PMID- 16289868
TI  - Prolonged blockade of NMDA or mGluR5 glutamate receptors reduces nigrostriatal
      degeneration while inducing selective metabolic changes in the basal ganglia
      circuitry in a rodent model of Parkinson's disease.
AB  - We compared the neuroprotective and metabolic effects of chronic treatment with
      ionotropic or metabotropic glutamate receptor antagonists, in rats bearing a
      unilateral nigrostriatal lesion induced by 6-hydroxydopamine (6-OHDA). The
      ionotropic, N-methyl-D-aspartate receptor antagonist MK-801 increased cell
      survival in the substantia nigra pars compacta (SNc) and corrected the metabolic
      hyperactivity (increased cytochrome oxidase activity) of the ipsilateral
      substantia nigra pars reticulata (SNr) associated with the lesion, but showed no
      effects on the 6-OHDA-induced hyperactivity of the subthalamic nucleus (STN).
      Significant-although less pronounced-protection of SNc neurons was also observed
      following treatment with the metabotropic glutamate receptor (mGluR5) antagonist
      2-methyl-6-(phenylehtynyl)-pyridine (MPEP). As opposed to MK-801, MPEP abolished
      the STN metabolic hyperactivity associated with the nigrostriatal lesion, without
      affecting SNr activity. Specific modulation of STN hyperactivity obtained with
      mGluR5 blockade may, therefore, open interesting perspectives for the use of this
      class of compounds in the treatment of Parkinson's disease.

PMID- 16289869
TI  - Phoneutria nigriventer omega-Phonetoxin IIA: a new tool for anti-calcium channel
      autoantibody assays in Lambert-Eaton myasthenic syndrome.
AB  - Lambert-Eaton myasthenic syndrome (LEMS) is a neurological autoimmune disease in
      which downregulation of voltage-gated calcium channels (VGCCs) leads to reduced
      acetylcholine release from motoneuron terminals. 70% of cases are paraneoplastic
      and rapid diagnosis of LEMS can result in early detection of the underlying
      tumor. Serological assays based on the capacity of autoantibodies to precipitate
      VGCCs labeled with radioligands provide valuable data. We have established a
      novel assay using the spider venom peptide 125I-omega-Phonetoxin IIA (125I
      omegaPtxIIA). 125I-omegaPtxIIA labeled recombinant Cav2.1 and Cav2.2 channels and
      endogenous VGCCs in rat brain membranes. Autoantibodies that immunoprecipitate a
      125I-omegaPtxIIA/channel complex were detected in 26/31 (84%) LEMS patients. The
      patients that were seropositive in the 125I-omegaPtxIIA assay corresponded
      precisely to the population that was positive for Cav2.1 and/or Cav2.2 antibodies
      detected using two different omega-conotoxins. Thus, the 125I-omegaPtxIIA assay
      detects a broader spectrum of autoantibody specificities than current omega
      conotoxin-based assays.

PMID- 16289870
TI  - Active immunization trial in Abeta42-injected P301L tau transgenic mice.
AB  - Amyloid beta-peptide (Abeta) containing plaques and neurofibrillary tangles (NFT)
      are the two major histopathological hallmarks of Alzheimer's disease (AD).
      According to the amyloid cascade hypothesis, deposition of Abeta is an initial
      and essential step in the pathogenesis of AD, and formation of NFT has been
      proposed to be caused by increased Abeta levels. Several previous studies
      revealed that Abeta plaque formation can be reduced or even prevented by active
      immunization with Abeta preparations or by administration of Abeta-specific
      antibodies. To assess the role of fibrillar preparations of Abeta42 in NFT
      formation, we previously performed intracerebral (i.c.) injections of Abeta42
      into brains of NFT-forming P301L tau transgenic mice which caused significant
      increases in NFT numbers. To determine whether these increases in NFT can be
      blocked or reduced by active immunization, P301L tau mice were immunized with
      intraperitoneal injections of preaggregated Abeta42. Abeta42-specific titers were
      monitored and the mice injected i.c. with Abeta42. We found that i.c. injection
      of Abeta42 caused significant increases in NFT formation. However, this induction
      was not affected by active immunization despite high serum anti-Abeta42 titer
      levels and binding of anti-Abeta42 antibodies to the injected Abeta42 aggregates.
      We conclude that active immunization is not sufficient to prevent the effect of
      Abeta42 on tau aggregation in our model system. Further studies are required to
      determine whether modifications of our protocol could affect the Abeta42-mediated
      induction of NFT formation.

PMID- 16289872
TI  - Dispersion optimization to enhance PHB production in fed-batch cultures of
      Ralstonia eutropha.
AB  - Despite its many useful properties, microbial production of poly-beta
      hydroxybutyrate (PHB) is not yet commercially competitive with synthetic
      polymers. One reason is inadequate optimization of the fermentation under
      industrial conditions. In this study, a physiologically reasonable and
      experimentally validated kinetic model for PHB synthesis by Ralstonia eutropha
      was incorporated into a dispersion model to simulate a large fed-batch
      bioreactor. Solutions of the model indicated that cell growth and PHB synthesis
      were maximum at Peclet numbers (Pe) between 20 and 30, representing limited
      finite dispersion. At these Peclet numbers, the optimum feed rates also showed
      lower consumptions of the substrates than at Pe=0. Since complete dispersion was
      also difficult to achieve in production-scale bioreactors, these results pointed
      to the possibility of exploiting controlled dispersion for productivity
      enhancement.

PMID- 16289871
TI  - How brains beware: neural mechanisms of emotional attention.
AB  - Emotional processes not only serve to record the value of sensory events, but
      also to elicit adaptive responses and modify perception. Recent research using
      functional brain imaging in human subjects has begun to reveal neural substrates
      by which sensory processing and attention can be modulated by the affective
      significance of stimuli. The amygdala plays a crucial role in providing both
      direct and indirect top-down signals on sensory pathways, which can influence the
      representation of emotional events, especially when related to threat. These
      modulatory effects implement specialized mechanisms of 'emotional attention' that
      might supplement but also compete with other sources of top-down control on
      perception. This work should help to elucidate the neural processes and temporal
      dynamics governing the integration of cognitive and affective influences in
      attention and behaviour.

PMID- 16289873
TI  - Application of response surface methodology for optimization of acidogenesis of
      cattail by rumen cultures.
AB  - Acidogenesis of cattail using rumen cultures was carried out to produce volatile
      fatty acids (VFA) in this study. The influences of pH and substrate concentration
      on cattail degradation, VFA yield and microbial growth were investigated by using
      response surface methodology (RSM). Experimental results showed that a low
      substrate concentration and pH of 6.9 were optimal for acidogenesis of cattail.
      The highest cattail degradation efficiency, VFA yield and microbial yield were
      75.9%, 0.41 g/g VS and 0.110 g/g VS, respectively. Further experiments confirmed
      that the main VFA in the acidogenesis of cattail were acetate, propionate and
      butyrate, while i-butyrate, valerate and i-valerate were also produced at low
      levels. The results suggested that acidogenesis using rumen cultures is a
      promising method for cattail disposal.

PMID- 16289874
TI  - Effect of retinoids and growth factor on in vitro bovine embryos produced under
      chemically defined conditions.
AB  - Experiments were conducted to investigate the beneficial effects of adding
      retinol (RT) and retinoic acid (RA) to bovine oocyte maturation media and insulin
      like growth factor-I (IGF-I) to embryo culture under chemically-defined
      conditions. In Experiment 1.1, in vitro maturation (IVM) was performed in basic
      maturation media (bMM) and supplemented with 0.3microM RT or 0.5microM RA. For
      embryo development presumptive zygotes and embryos were placed in droplets of
      potassium simplex optimized medium (KSOM). Addition of RT and RA to bMM improved
      (p<0.05) blastocyst formation as compared with control treatments. In Experiment
      1.2, using embryos originating from oocytes previously treated with RT and RA,
      the presumptive zygotes were placed in droplets of KSOM and embryos (2-4 cells)
      in droplets of fresh KSOM supplemented or not with IGF-I. The number of 2-4-cell
      stage embryos developing to the blastocyst and expanded blastocyst stages were
      greater (p<0.05) when embryo culture media was supplemented with IGF-I. In
      Experiment 2.1, IVM was conducted with bMM+FSH containing 0.3microM RT or
      0.5microM RA. For embryo development, presumptive zygotes were placed in droplets
      of KSOM. Addition of RT or RA to IVM medium also enhanced (p<0.05) blastocyst
      formation. The supplementation of embryo culture media with IGF-I resulted in a
      greater number (p<0.05) of 2-4-cell stage embryos developing into blastocysts,
      expanded blastocysts and hatched blastocysts. In Experiment 2.2, using embryos
      originating from oocytes previously treated with RT and RA, presumptive zygotes
      were also placed in droplets of KSOM and embryos (2-4 cells) in droplets of fresh
      KSOM supplemented or not with IGF-I. The supplementation of embryo culture media
      with IGF-I resulted in a greater (p<0.05) number of 2-4-cell stage embryos
      developing to the blastocyst, expanded blastocyst and hatched blastocyst stages.

PMID- 16289875
TI  - Identification of BCOX1, a novel gene overexpressed in breast cancer.
AB  - The identification of tumor-associated antigens, which are specifically expressed
      in cancer tissues, is of utmost important for immunotherapy of breast cancer. We
      have combined in silico screening and experimental expression analysis to
      identify genes that are differentially expressed in breast carcinomas compared
      with their corresponding normal tissues. Using these approaches, we identified a
      novel gene, BCOX1, with overexpression in breast carcinoma. BCOX1 was highly
      homologous to KIAA0100, a hypothetical gene located on chromosome 17q11.2. RNA in
      situ hybridization shows that BCOX1 mRNA signal is mainly located in the
      cytoplasm of breast carcinoma epithelial cells, but not in those of normal
      epithelial cells, stroma cells and lymphocytes. Furthermore, mRNA expression of
      BCOX1 was moderately elevated in ductal in situ carcinoma (DCIS), peaked in
      invasive breast carcinoma (IBC) and metastatic breast carcinoma cells (MET)
      whereas absent in benign ductal epithelial cells. The predicted BCOX1 open
      reading frame of 666 bp encodes a putative protein of 222 amino acid residues
      with a calculated molecular weight of 2,4920 Da and a PI of 5.86. Computational
      analyses predict that the putative BCOX1 protein is a cytoplasmic protein. The
      functional relevance of this novel gene is yet to be determined. This study
      warrants further investigations to explore the molecular functions of BCOX1, and
      to determine its potential diagnostic and therapeutic applications for breast
      cancer.

PMID- 16289876
TI  - Cryptotanshinone inhibits endothelin-1 expression and stimulates nitric oxide
      production in human vascular endothelial cells.
AB  - The Chinese herb Salvia miltiorrhiza (SM) has been found to have beneficial
      effects on the circulatory system. In the present study, we investigated the
      effects of cryptotanshinone (derived from SM) on endothelin-1 (ET-1) expression
      in human umbilical vein endothelial cells (HUVECs). The effect of
      cryptotanshinone on nitric oxide (NO) in HUVECs was also examined. We found that
      cryptotanshinone inhibited basal and tumor necrosis factor-alpha (TNF-alpha)
      stimulated ET-1 secretion in a concentration-dependent manner. Cryptotanshinone
      also induced a concentration-dependent decrease in ET-1 mRNA expression.
      Cryptotanshinone increased basal and TNF-alpha-attenuated NO production in a dose
      dependent fashion. Cryptotanshinone induced a concentration-dependent increase in
      endothelial nitric oxide synthase (eNOS) expression without significantly
      changing neuronal nitric oxide synthase (nNOS) expression in HUVECs in the
      presence or absence of TNF-alpha. NOS activities in the HUVECs were also induced
      by cryptotanshinone. Furthermore, decreased ET-1 expression in response to
      cryptotanshinone was not antagonized by the NOS inhibitor l-NAME. A gel shift
      assay further showed that TNF-alpha-induced Nuclear Factor-kappaB (NF-kappaB)
      activity was significantly reduced by cryptotanshinone. These data suggest that
      cryptotanshinone inhibits ET-1 production, at least in part, through a mechanism
      that involves NF-kappaB but not NO production.

PMID- 16289877
TI  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) level in human hair as
      biomarkers for dietary grilled/stir-fried meat and fish intake.
AB  - Several case-control studies have reported possible associations between
      heterocyclic amine (HCA) intake and the risk of cancer. However, the validity of
      a questionnaire to assess HCA intake has hardly been examined. In particular, no
      biomarker which could serve as an independent measure of habitual HCA intake has
      been established. Therefore, the validity of a questionnaire to assess HCA intake
      by means of a biomarker remains to be investigated. In this study, we examined
      the availability of hair HCAs as a biochemical indicator of dietary intake of
      HCAs. Study subjects were 20 volunteers (7 men and 13 women) aged 25-57 years,
      either residents of Tokyo or the neighboring cities in Japan. We collected
      individual weighed dietary records (DR) over 28 consecutive days. Approximately 3
      5 g of hair was collected twice from all subjects before and after DR at
      intervals of 1-3 months. The mean (S.D.) 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP) level of hair was 1376.0 pg/g hair (928.9) and 16.6 ng/g
      melanin (12.3). A steady increase in the mean PhIP level in hair from the lowest
      to the highest tertile of the grilled/stir-fried meat intake was observed (P =
      0.009), but not in the grilled/stir-fried fish intake (P = 0.461). The PhIP level
      in hair was highly correlated with the grilled/stir-fried meat intake (r = 0.68)
      but not with the grilled/stir-fried fish intake (r = 0.28). These observations
      were made of hair with and without melanin adjustment. The present study
      indicates that the PhIP level in hair can be used as a biological indicator of
      dietary intake of HCAs.

PMID- 16289878
TI  - Conversion of potent MMP inhibitors into selective TACE inhibitors.
AB  - Novel sultam hydroxamates with potent MMP activity were transformed into potent
      TACE inhibitors, lacking MMP activity. To accomplish this we relied on structural
      differences between the MMP and TACE S1' pockets and the known advantageous fit
      of a 2-methyl-4-quinolinylmethoxyphenyl group into this region. From this
      approach, compound 7d was identified as a potent TACE inhibitor (IC50 = 3.7 nM)
      that lacked MMP-1, -2, -9, and -13 activity.

PMID- 16289879
TI  - PTP-1B inhibitors: cyclopenta[d][1,2]-oxazine derivatives.
AB  - A series of novel cyclopenta[d][1,2]-oxazine derivatives was prepared and
      evaluated for their inhibitory activity toward protein tyrosine phosphatase 1B
      (PTP-1B). Compound 6s was found to be an inhibitor of PTP-1B with nanomolar
      IC(50) value and high level of selectivity over other recombinant phosphatases.

PMID- 16289880
TI  - Molecular cloning, characterization and expression of a novel Asr gene from
      Ginkgo biloba.
AB  - A new abscisic acid, stress and ripening (Asr) gene was cloned from Ginkgo biloba
      by rapid amplification of cDNA ends (RACE) method. The full-length cDNA of G.
      biloba Asr (designated as GbAsr) was 952 bp long and it contained a 543 bp open
      reading frame encoding a protein of 181 amino acids. GbASR was found to be rich
      in His, Lys, Glu and Ala, and it had extensive homology with those of other plant
      Asr genes via multiple alignment analysis. Phylogenetic tree analysis indicated
      that the GbASR had a closer relationship with ASR from pine, another gymnosperm
      species, than with angiosperm ASRs. Southern blot analysis indicated that GbAsr
      belonged to a small multigene family. RT-PCR analyses revealed that GbAsr had a
      distinct up-regulated transcript pattern in root, stem and leaf under mannitol,
      NaCl and ABA treatments. The recombinant GbASR protein was successfully expressed
      in E. coli strain with pET-32a vector, and the result showed that the molecular
      weight of the recombinant protein was about 20 kDa, a size in agreement with that
      of the predicted by bioinformatic analysis. The expression of the GbAsr in E.
      coli will facilitate further research on this gene.

PMID- 16289881
TI  - Film drying and complexation effects in the simultaneous skin permeation of
      ketoprofen and propylene glycol from simple gel formulations.
AB  - This work investigated the simultaneous permeation of ketoprofen and propylene
      glycol (PG) across pig ear skin from simple gel formulations administered under
      simulated in-use conditions. The aims were to quantify rates of permeation of
      both solvent and active, probe the effects of formulation drying and gain insight
      into drag/complexation interactions. Simple 3-component gels were formulated
      using a fixed amount of ketoprofen and hydroxypropyl cellulose thickener with
      decreasing content of solvent propylene glycol. Multiple finite (5 mg x 15 mg)
      doses were massaged over 24h into full thickness pig ear skin in vertical Franz
      type diffusion cells. The permeation of ketoprofen was inversely proportional to
      the content of PG, whereas the permeation of PG was directly proportional,
      although the amount of PG permeated was always greater than ketoprofen, even from
      the driest gel practically achievable. In this state, the molar ratio of
      PG/ketoprofen was approximately 12, suggesting that this number of PG molecules
      constitutes the solvation cage of ketoprofen. Dragging/pulling effect extends
      throughout the skin and into the receptor compartment and probably the system, in
      an in vivo situation. Although PG may represent a worse case scenario given its
      well-documented skin permeation enhancement properties, it is probable that other
      solvents exert a similar effect on solutes across skin. A drying film will behave
      in different ways depending on the nature of both the thickener and solvent,
      where the outcomes are not readily predictable. It is important to account for
      the fate of all species administered from a topical formulation.

PMID- 16289882
TI  - Nanoparticle formulation may affect the stabilization of an antiischemic prodrug.
AB  - The prodrug 5'-octanoyl-CPA (Oct-CPA) of the antiischemic N6-cyclopentyladenosine
      (CPA) has been encapsulated by nanoprecipitation in poly(lactic acid)
      nanoparticles, which have been recovered by gel-filtration, ultra-centrifugation
      or dialysis. We have analysed how different surfactants and purification methods
      can influence the nanoparticle characteristics. The particle sizes have been
      obtained by scanning electron microscope, whereas a SdFFF system was employed to
      detect their distributions. The Oct-CPA release from nanoparticles and
      stabilities in human blood of free and encapsulated prodrug have been analysed by
      HPLC techniques. The effects of nanoparticles on CPA interaction toward adenosine
      A1 receptor (its action site) have been analysed using radiolabelled drugs. The
      smallest nanoparticles and the best degree of homogeneity have been obtained
      using sodium cholate; the best recovery has been achieved by dialysis, whereas
      gel-filtration and ultra-centrifugation have induced the greatest removal of
      surfactants. The release of Oct-CPA was better controlled from the nanoparticles
      obtained using Pluronic F68 and purified by gel-filtration or ultra
      centrifugation. Similarly, these nanoparticles better increased the stability of
      the prodrug in human blood. In particular, the nanoparticles purified by ultra
      centrifugation induced a strong stability to a fraction of the encapsulated Oct
      CPA. Any interference by unloaded nanoparticles has been registered for CPA
      adenosine A1 receptor interaction.

PMID- 16289883
TI  - Dopamine D1 or D2 receptor antagonism within the basolateral amygdala
      differentially alters the acquisition of cocaine-cue associations necessary for
      cue-induced reinstatement of cocaine-seeking.
AB  - The basolateral amygdala complex has been implicated in the formation and
      utilization of cocaine-cue associations in rat models of cue-induced
      reinstatement to cocaine-seeking behavior. We have previously demonstrated the
      importance of dopamine inputs to the basolateral amygdala complex in the
      reinstatement of cocaine-seeking behavior following chronic cocaine self
      administration. Here we show that selective blockade of amygdalar dopamine D1 and
      D2 receptors during acquisition of cocaine-cue associations has distinctive
      effects on subsequent conditioned-cued cocaine-seeking behavior. Male, Sprague
      Dawley rats were first trained to self-administer i.v. cocaine on a fixed ratio 1
      schedule for 5 days. Subjects then received bilateral, intra-basolateral amygdala
      complex infusions of a dopamine D1 receptor antagonist (SCH23390, 0.25-2.0
      microg/side; experiment 1), a dopamine D2 receptor antagonist (raclopride, 0.625
      5.0 microg/side; experiment 2), or vehicle just prior to a single classical
      conditioning session, during which a light+tone cue was discretely paired with
      passive infusions of cocaine in the absence of lever responding. Following five
      additional days of cocaine self-administration and 7-10 days of extinction
      training, animals underwent multiple tests for cue-induced reinstatement.
      SCH23390 (2.0 microg/side), administered at the time of cocaine-cue association
      only, produced an attenuation of reinstatement to cue-induced cocaine-seeking
      behavior. In contrast, low doses of raclopride potentiated, while a higher dose
      of raclopride attenuated cue-induced reinstatement. These results demonstrate
      unique contributions of D1 vs. D2 receptors in mediating dopamine inputs within
      the basolateral amygdala complex during the formation of cocaine-stimulus
      associations that are critical for cue-induced reinstatement.

PMID- 16289884
TI  - Effects of barbiturates on ATP-sensitive K channels in rat substantia nigra.
AB  - ATP-sensitive K channels are widely expressed in cytoplasmic membranes of
      neurons, and they couple cell metabolism to excitability. They are thought to be
      involved in neuroprotection against cell damage during hypoxia, ischemia and
      excitotoxicity by hyperpolarizing neurons and reducing excitability. Although
      barbiturates are often used in patients with brain ischemia, the effects of these
      agents on neuronal ATP-sensitive K channels have not been clarified. We studied
      the effects of thiopental and pentobarbital on surface ATP-sensitive K channels
      in principal neurons of rat substantia nigra pars compacta. Whole cell voltage-
      and current-clamp recordings were made using rat midbrain slices. ATP-sensitive K
      channels were activated by intracellular dialysis with an ATP-free pipette
      solution during perfusion with a glucose-free solution. When the pipette solution
      contained 4mM ATP and the perfusing solution contained 25 mM glucose, the
      membrane current at -60 mV remained stable. When intracellular ATP was depleted,
      hyperpolarization and an outward current developed slowly. Although thiopental
      did not affect the membrane current in the presence of ATP and glucose, it
      reversibly inhibited the hyperpolarization and outward current induced by
      intracellular ATP depletion at 100 and 300 microM. Thiopental reduced the ATP
      depletion-induced outward current by 4.7%, 36.7% and 87% at 30, 100 and 300
      microM, respectively. The high dose of pentobarbital also exhibited similar
      effects on ATP-sensitive K channels. These results suggest that barbiturates at
      high concentrations but not at clinically relevant concentrations inhibit ATP
      sensitive K channels activated by intracellular ATP depletion in rat substantia
      nigra.

PMID- 16289885
TI  - Selective down-regulation of [(125)I]Y0-alpha-conotoxin MII binding in rat
      mesostriatal dopamine pathway following continuous infusion of nicotine.
AB  - Prolonged exposure to nicotine, as occurs in smokers, results in up-regulation of
      all the neuronal nicotinic acetylcholine receptor subtypes studied so far, the
      only differences residing in the extent and time course of the up-regulation.
      alpha6beta2*-Nicotinic acetylcholine receptors are selectively enriched in the
      mesostriatal dopaminergic system and may play a crucial role in nicotine
      dependence. Here we show that chronic nicotine treatment (3mg/kg/day for two
      weeks, via s.c. osmotic minipumps) caused a significant decrease (36% on average)
      in the binding of [(125)I]Y(0)-alpha-conotoxin MII (a selective ligand for
      alpha6beta2*-nicotinic acetylcholine receptors in this system) to all the five
      regions of the rat dopaminergic pathway analyzed in this study. After one week of
      withdrawal, binding was still lower than control in striatal terminal regions
      (namely the caudate putamen and the accumbens shell and core). In somatodendritic
      regions (the ventral tegmental area and the substantia nigra) the decrease was
      significant at the end of the treatment and recovered within one day of
      withdrawal. This effect was not due to displacement of [(125)I]Y(0)-alpha
      conotoxin MII binding by residual nicotine. In fact the binding was not changed
      by 565 ng/g nicotine (obtained with a single injection of nicotine), a
      concentration much higher than that found in the brain of rats chronically
      treated with nicotine (240 ng/g). In addition, consistent with previous studies
      reporting an up-regulation of other subtypes of nicotinic acetylcholine
      receptors, we found that nicotine exposure significantly increased (40% on
      average) the binding of [(125)I]epibatidine (a non-selective agonist at most
      neuronal heteromeric nicotinic acetylcholine receptors) in three up to five
      regions containing only alpha-conotoxin MII-insensitive [(125)I]epibatidine
      binding sites, namely the primary motor, somatosensory and auditory cortices. In
      conclusion, this work is the first to demonstrate that alpha6beta2*-nicotinic
      acetylcholine receptors, unique within the nicotinic acetylcholine receptor
      family, are down-regulated following chronic nicotine treatment in rat
      dopaminergic mesostriatal pathway, a finding that may shed new light in the
      complex mechanisms of nicotine dependence.

PMID- 16289886
TI  - The survival of vagal and glossopharyngeal sensory neurons is dependent upon
      dystonin.
AB  - The vagal and glossopharyngeal sensory ganglia and their peripheral tissues were
      examined in wild type and dystonia musculorum mice to assess the effect of
      dystonin loss of function on chemoreceptive neurons. In the mutant mouse, the
      number of vagal and glossopharyngeal sensory neurons was severely decreased (70%
      reduction) when compared with wild type littermates. The mutation also reduced
      the size of the circumvallate papilla (45% reduction) and the number of taste
      buds (89% reduction). In addition, immunohistochemical analysis demonstrated that
      the dystonin mutation reduced the number of PGP 9.5-, calcitonin gene-related
      peptide-, P2X3 receptor- and tyrosine hydroxylase-containing neurons. Their
      peripheral endings also decreased in the taste bud and epithelium of
      circumvallate papillae. These data together suggest that the survival of vagal
      and glossopharyngeal sensory neurons is dependent upon dystonin.

PMID- 16289887
TI  - Mapping brain activity following administration of a nicotinic acetylcholine
      receptor agonist, ABT-594, using functional magnetic resonance imaging in awake
      rats.
AB  - Administration of ABT-594, a potent agonist for nicotinic acetylcholine receptors
      with selectivity for the alpha4beta2 receptor subtype, is known to modulate a
      diverse array of behaviors including those associated with nociception, anxiety
      and motor function. In this study, we sought to gain insight into the neural
      actions of ABT-594, in vivo, by conducting functional magnetic resonance imaging
      in awake and anesthetized rats. Using T(2)*-weighted gradient echo imaging and an
      ultrasmall superparamagnetic iron oxide contrast agent, functional imaging was
      conducted on a 4.7 T magnet to measure changes in relative cerebral blood volume.
      In awake, restrained, male Sprague-Dawley rats that were acclimated to the
      imaging environment, injection of ABT-594 (0.03-0.3 micromol/kg, i.v.) evoked
      changes to relative cerebral blood volume in several neural regions including the
      cingulate, somatosensory, motor, auditory, and pre-frontal cortices as well as
      the thalamus and the periaqueductal gray/dorsal raphe. These effects were
      typically bimodal with significant decreases in relative cerebral blood volume at
      the 0.03 micromol/kg dose and increases at the higher doses (0.1 and 0.3
      micromol/kg). The decreases and increases in relative cerebral blood volume were
      often observed within the same region, but triggered by different doses. Both
      increases and decreases in relative cerebral blood volume were blocked by
      pretreatment with the noncompetitive nicotinic acetylcholine receptor antagonist,
      mecamylamine (5 micromol/kg, i.p.) in awake rats. Administration of ABT-594 (0.1
      micromol/kg, i.v.) to alpha-chloralose-anesthetized rats did not significantly
      alter relative cerebral blood volume in any brain region suggesting an anesthetic
      related interference with the effects of ABT-594. The neural regions affected by
      administration of ABT-594 corresponded well to the known pre-clinical behavioral
      profile for this compound, and demonstrate the utility of using functional
      magnetic resonance imaging in awake animals to study pharmacological action.

PMID- 16289889
TI  - Comparison of motor strategies in sit-to-stand and back-to-sit motions between
      healthy and Alzheimer's disease elderly subjects.
AB  - We studied the kinematics of shoulder displacement during sit-to-stand and back
      to-sit in 6 healthy elderly subjects and six elderly subjects with mild to
      moderate Alzheimer's disease in order to elucidate the impact of Alzheimer's
      disease on motor planning and control processes. During sit-to-stand, Alzheimer's
      disease subjects reduced their forward displacement and started their upward
      displacement earlier than healthy elderly subjects. Furthermore, shoulder path
      curvatures were more pronounced for upward compared with downward displacement in
      healthy elderly group, in contrast with Alzheimer's disease group. Temporal
      analysis found that: 1) for both groups, profiles of velocity of sit-to-stand and
      back-to-sit showed two peaks corresponding respectively to forward/upward and to
      downward/backward displacements, 2) peaks of velocity were almost comparable
      between the two groups, 3) duration of sit-to-stand was shorter than duration of
      back-to-sit in the two groups and 4) duration of sit-to-stand and back-to-sit was
      shorter in Alzheimer's disease group than in healthy elderly group. However,
      dissimilarities were observed for transition and deceleration phases during sit
      to-stand, and for acceleration and transition phases during back-to-sit, between
      the two groups. Interestingly, while sit-to-stand and back-to-sit differed in
      healthy elderly subjects during transition and deceleration phases, such a
      difference was not observed for Alzheimer's disease subjects. So, our study
      showed that invariant spatio-temporal movement parameters in the two groups
      differed, while non-invariant parameters did not, and suggests that higher level
      motor process of whole body motions are affected by Alzheimer's disease, while
      lower level motor features remain intact.

PMID- 16289888
TI  - Developmental abnormalities in the Nuc1 rat retina: a spontaneous mutation that
      affects neuronal and vascular remodeling and retinal function.
AB  - The retina serves as an excellent model in which to study vertebrate CNS
      development. We have discovered a spontaneous mutation in the Sprague-Dawley rat
      that results in a novel and unusual ocular phenotype, including retinal
      abnormalities, that we have named Nuc1. We have previously shown that the Nuc1
      mutation appears to suppress programmed cell death in the developing retina. Here
      we report that maturation of both the retinal neurons and the retinal vessels is
      abnormal in Nuc1 homozygous rats. The developmental changes in the retinal
      neurons and vasculature are correlated with regard to degree of abnormality. As
      Nuc1 homozygotes mature, focal retinal detachment begins at approximately 3
      months after birth, and near total traction retinal detachment, associated with
      pre-retinal fibrosis and neovascularization, is evident by 18 months.
      Electroretinographic studies at 2.5 months of age indicate that functional
      retinal degeneration precedes retinal detachment. The functional abnormality is
      most evident in rods and the inner retina, and is present in homozygous but not
      heterozygous mutants. Immunocytochemical studies of rod and cone photoreceptors
      indicate abnormalities in rod, but not cone, photoreceptors in Nuc1 homozygotes,
      consistent with the electroretinographic findings. In Nuc1 animals, the Muller
      cells are activated. Although such activation may result from inflammation,
      Muller cells in Nuc1 may be reacting to a neuronal influence. It appears that the
      Nuc1 mutation plays a regulatory role in both developing and maturing ocular
      tissues. The Nuc1 mutation may also serve as an important genetic tool to explore
      the relationships that may exist among gliosis, normal neuronal development, and
      normal vascular development and how abnormalities in these associations lead to
      common retinal diseases.

PMID- 16289890
TI  - Neurogenesis in adolescent brain is potently inhibited by ethanol.
AB  - Adolescence is a period of progressive changes in brain that likely contribute to
      the maturation of behavior. Human adolescents consume large amounts of ethanol.
      To investigate the effects of ethanol on adolescent neural progenitor cells, male
      rats (35-40 days old) were treated with an acute dose of ethanol (1.0, 2.5 or 5.0
      g/kg, i.g.) or vehicle that resulted in peak blood levels of 33, 72, and 131
      mg/dl, respectively. Bromodeoxyuridine (300 mg/kg i.p.) was administered to label
      dividing cells and rats were killed at 5 h to assess proliferation or at 28 days
      to assess cell survival and differentiation. After 5 h, bromodeoxyuridine
      immunoreactivity was reduced by 63, 97 and 99% in the rostral migratory stream
      and 34, 71 and 99% in the subventricular zone by 1.0, 2.5 and 5.0 g/kg of ethanol
      respectively. In the dentate gyrus, ethanol reduced bromodeoxyuridine
      immunoreactivity by 29, 40, and 78% at the three doses respectively. The density
      of doublecortin immunoreactivity was decreased after 3 days and the number of
      bromodeoxyuridine+ cells remained decreased at 28 days when most hippocampal
      bromodeoxyuridine+ cells coexpressed neuronal nuclei, a neuronal marker. These
      studies indicate that the adolescent brain is very sensitive to acute ethanol
      inhibition of neurogenesis.

PMID- 16289891
TI  - Use of the exogenous Drosophila octopamine receptor gene to study Gq-coupled
      receptor-mediated responses in mammalian neurons.
AB  - Diverse excitatory and inhibitory neuronal responses are mediated via Gq-coupled
      receptors, but the lack of a systematic comparison of different receptors or
      neurons has hindered a better understanding of these responses. Such a comparison
      may be provided by an exogenous receptor that is activated by compounds that have
      no effect on endogenous receptors. We therefore expressed an invertebrate
      biogenic amine receptor, the Drosophila octopamine receptor, in rat cortical
      neurons and compared octopamine receptor-mediated responses with those mediated
      by the group I metabotropic glutamate receptor, the endogenous Gq-coupled
      receptor in rat cortical neurons. Stimulation of either receptor did not result
      in a calcium response in octopamine receptor-expressing neurons, although
      octopamine preferentially elicited a calcium increase in octopamine receptor
      expressing PC12h cells, while enhancing the neuronal depolarization-induced
      calcium increase and the electrical excitability. The increased excitability was
      caused by inward currents resulting from a reduction in the leak current, which
      was voltage-independent and blocked by genistein, a non-selective tyrosine kinase
      inhibitor. These results show that, in cortical neurons, exogenous octopamine
      receptor in mushroom bodies activated the same cell signaling pathway as
      endogenous metabotropic glutamate receptor, suggesting that the diverse neuronal
      responses mediated by Gq-coupled receptors are due to the properties of different
      neurons, rather than to the properties of the receptors.

PMID- 16289892
TI  - Alpha-linolenic acid and riluzole treatment confer cerebral protection and
      improve survival after focal brain ischemia.
AB  - We investigated here the effects of alpha-linolenic acid and riluzole, both
      activators of the 2P-domain K+ channel family TREK/TRAAK, in a model of focal
      ischemia clinically relevant to stroke, not only assessing neuronal protection,
      but also long term survival. Moreover, all the drug treatments were initiated
      post-ischemia. Mice were subjected to transient middle cerebral artery occlusion
      (1 h) and reperfusion according to the intraluminal filament model. Drugs were
      injected into the jugular vein according to three protocols: (i) a single dose of
      4 mg/kg riluzole or 500 nmol/kg alpha-linolenic acid at different reperfusion
      time; (ii) a three-day therapy (a single dose of 2 mg/kg riluzole and 250 nmol/kg
      alpha-linolenic acid given 1-2, 48 and 72 h after reperfusion); (iii) a three
      week therapy (a single dose of 2 mg/kg riluzole and 250 nmol/kg alpha-linolenic
      acid given once a week during three weeks after reperfusion. A combined treatment
      with 2mg/kg riluzole+250 nmol/kg alpha-linolenic acid injected 2 h after
      reperfusion was also tested. A single dose of riluzole (4 mg/kg) or alpha
      linolenic acid (500 nmol/kg) injected up to 3 h after reperfusion reduced
      drastically the stroke volume by 75% and 86%, respectively. Neurological deficits
      24 h after ischemia were significantly improved by alpha-linolenic acid500 or
      riluzole4 with a neurological score of 1.8 as compared with 2.5 observed in
      vehicle-treated mice. Alpha-linolenic acid- and riluzole treatment were
      associated with a reduction in cytopathological features of cell injury,
      including DNA fragmentation and Bax expression in the cortex and the caudate
      putamen. With regard to the survival rate at 30 days, the best protections were
      obtained with the alpha-linolenic acid-injection in the three-week therapy as
      well as with a single dose of the combined treatment (2 mg/kg riluzole+250
      nmol/kg alpha-linolenic acid). Palmitic acid, a saturated fatty acid that does
      not activate the 2P-domain K-channel TREK/TRAAK family, did not provide any
      neuroprotection. Taken together, these data suggest that the TREK/TRAAK K-channel
      family may be a promising target for neuroprotection, and that riluzole and alpha
      linolenic acid could be of therapeutic value against focal ischemia/reperfusion
      injury to the brain.

PMID- 16289894
TI  - The role of FABP2 gene polymorphism in alcoholic cirrhosis.
AB  - Hypertriglyceridemia and dietary lipids have been suggested to modulate the
      severity of alcoholic liver disease and the progression to alcoholic cirrhosis
      (AC). The intestinal fatty acid binding protein (IFABP) is the main transporter
      of dietary fatty acids into the enterocyte and has a genetic polymorphism, FABP2
      A54T that has been associated with hypertriglyceridemia. We determined the
      frequency of the FABP2 gene polymorphism using PCR-RFLP and measured serum
      triglycerides, HDL, LDL, total lipids and cholesterol in 67 patients with AC and
      in 124 unrelated healthy individuals. Frequencies of genotypes and alleles were
      similar between the two groups. The healthy subjects, who were homozygous for the
      Thr54 genotype had significantly higher mean triglyceride serum concentrations
      than those homozygous for the Ala54 genotype (P<0.05). However, AC patients who
      were homozygous for the Thr54 genotype, had lower mean triglyceride serum
      concentrations (P<0.01), and had a significantly longer period of continued
      alcohol abuse prior to the diagnosis of liver cirrhosis compared to the AC
      patients homozygous for the Ala54 genotype (P<0.05). Our data suggests that the
      polymorphism Thr54 of the FABP2 gene is associated with a later onset of AC in
      the lower economic status Mexican population studied.

PMID- 16289893
TI  - 2-Chloro-N-[(S)-phenyl [(2S)-piperidin-2-yl] methyl]-3-trifluoromethyl benzamide,
      monohydrochloride, an inhibitor of the glycine transporter type 1, increases
      evoked-dopamine release in the rat nucleus accumbens in vivo via an enhanced
      glutamatergic neurotransmission.
AB  - 2-Chloro-N-S-phenyl 2S-piperidin-2-yl methyl]-3-trifluoromethyl benzamide,
      monohydrochloride (SSR504734) is a potent and selective inhibitor of the glycine
      transporter type 1, which increases central N-methyl-D aspartate glutamatergic
      tone. Since glutamate has been shown to play a role in the regulation of the
      dopaminergic system in dopamine-related disorders, such as schizophrenia, we
      investigated the possibility that SSR504734 may modify the basolateral amygdala
      elicited stimulation of dopamine release in the nucleus accumbens via an
      augmentation of glutamate receptor-mediated neurotransmission. First, our data
      confirmed that SSR504734 is an inhibitor of GlytT1. In the nucleus accumbens of
      anesthetized rat, SSR504734 (10 mg/kg, i.p.) induced an increase of extracellular
      levels of glycine as measured by microdialysis coupled with capillary
      electrophoresis with laser-induced fluorescence detection. Second, the data
      demonstrated that SSR504734 (10 mg/kg, i.p.) enhanced the facilitatory influence
      of glutamatergic afferents on dopamine neurotransmission in the nucleus
      accumbens. Using an electrochemical technique, we measured dopamine release in
      the nucleus accumbens evoked by an electrical stimulation of the basolateral
      amygdala. SSR504734 facilitated dopamine release evoked by a 20 or a 40 Hz
      frequency basolateral amygdala stimulation. This facilitatory effect was
      dependent on glutamatergic tone, as intra-nucleus accumbens application of 6-7
      dinitroquinoxaline-2,3-dione (10(-3) M) or DL-2-amino-5-phosphonopentanoic acid
      (10(-3) M), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and N-methyl
      D aspartate receptors antagonists, respectively, inhibited dopamine release
      evoked by basolateral amygdala stimulation. Furthermore DL-2-amino-5
      phosphonopentanoic acid co-administrated with SSR504734 hampered the dopamine
      evoked release facilitation. These data underline the in vivo implication of the
      glycine uptake mechanism in the control of subcortical glutamate/dopamine
      interactions.

PMID- 16289895
TI  - Serum HGF levels and acute liver failure.

PMID- 16289896
TI  - The early history of myasthenia gravis.
AB  - Myasthenia gravis was first recognised as a distinct clinical entity by Thomas
      Willis, a 17th century Oxford physician, whose 1672 account in Latin was largely
      unnoticed until 1903. The first modern description was made in 1877 by Samuel
      Wilks, a London physician. Towards the close of the 19th century, primary muscle
      diseases and diseases due to denervation of muscle were studied by English,
      French, and German physicians. The first full descriptions of myasthenia gravis
      were by Wilhelm Erb, of Heidelberg, and Samuel Goldflam of Warsaw. The account by
      Willis, and the 19th century literature of myasthenia gravis are reviewed,
      revealing the dominance of German physicians and neuropathologists in the early
      understanding of the disease. The development in pathology, aetiology, and
      therapy in the first half of the 20th century are described.

PMID- 16289897
TI  - Alpha-dystroglycan, the usual suspect?
AB  - An increasing number of congenital muscular dystrophies might originate from
      genetic abnormalities of glycosyltransferases genes which are believed to target
      the alpha subunit of the dystroglycan (DG) adhesion complex as their major
      enzymatic substrate. alpha-DG is highly glycosylated and peripherally associated
      with the sarcolemma of skeletal muscle and the plasma membrane in a wide variety
      of cells. Several lines of evidence indicate that alpha-DG hypoglycosylation
      might represent the primary molecular event characterizing congenital
      dystrophies, since it is likely to alter alpha-DG high-affinity binding to
      laminin and other extracellular molecules, thus negatively influencing the
      basement-membrane/cytoskeleton axis and eventually leading to sarcolemmal
      instability, infiltration of myofibers and congenital weakness. For this reason,
      congenital diseases such as Walker-Warburg Syndrome or Muscle-Eye-Brain disease,
      have been recently denominated 'secondary dystroglycanopathies'. However, some
      crucial points need to be fully addressed in order to finally assess the degree
      of involvement of alpha-DG in congenital muscular diseases, for example: the
      possibility that mutations hitting the DG gene might lead to primary
      dystroglycanopathies; the putative functional or pathological role of
      hypoglycosylated - or even hyperglycosylated - alpha-DG molecules; or also the
      compensatory role played by the recently identified paralogue
      glycosyltransferases in alpha-DG sugar decoration.

PMID- 16289898
TI  - Evolution of myelin proteolipid proteins: gene duplication in teleosts and
      expression pattern divergence.
AB  - The coevolution of neurons and their supporting glia to the highly specialized
      axon-myelin unit included the recruitment of proteolipids as neuronal
      glycoproteins (DMbeta, DMgamma) or myelin proteins (DMalpha/PLP/DM20). Consistent
      with a genome duplication at the root of teleosts, we identified three
      proteolipid pairs in zebrafish, termed DMalpha1 and DMalpha2, DMbeta1 and
      DMbeta2, DMgamma1 and DMgamma2. The paralogous amino acid sequences diverged
      remarkably after gene duplication, indicating functional specialization. Each
      proteolipid has adopted a distinct spatio-temporal expression pattern in neural
      progenitors, neurons, and in glia. DMalpha2, the closest homolog to mammalian
      PLP/DM20, is coexpressed with P0 in oligodendrocytes and upregulated after optic
      nerve lesion. DMgamma2 is expressed in multipotential stem cells, and the other
      four proteolipids are confined to subsets of CNS neurons. Comparing protein
      sequences and gene structures from birds, teleosts, one urochordate species, and
      four invertebrates, we have reconstructed major steps in the evolution of
      proteolipids.

PMID- 16289899
TI  - Tachykinin-related peptides modulate odor perception and locomotor activity in
      Drosophila.
AB  - The invertebrate tachykinin-related peptides (TKRPs) constitute a conserved
      family, structurally related to the mammalian tachykinins, including members such
      as substance P and neurokinins A and B. Although their expression has been
      documented in the brains of insects and mammals, their neural functions remain
      largely unknown, particularly in behavior. Here, we have studied the role of
      TKRPs in Drosophila. We have analyzed the olfactory perception and the locomotor
      activity of individuals in which TKRPs are eliminated in the nervous system
      specifically, by using RNAi constructs to silence gene expression. The perception
      of specific odorants and concentrations is modified towards a loss of
      sensitivity, thus resulting in a significant change of the behavioral response
      towards indifference. In locomotion assays, the TKRP-deficient flies show
      hyperactivity. We conclude that these peptides are modulators of olfactory
      perception and locomotion activity in agreement with their abundant expression in
      the olfactory lobes and central complex. In these brain centers, TKRPs seem to
      enhance the regulatory inhibition of the neurons in which they are expressed.

PMID- 16289900
TI  - Head injuries of Roman gladiators.
AB  - Gladiator remains from a recently unearthed cemetery in ancient Ephesus (Turkey)
      offer a unique opportunity for proving common theories involving the weaponry and
      techniques of gladiator fighting based on the evidence supplied by cranial bones.
      This mass grave is the first of its kind to undergo a thorough osteological and
      forensic examination. A minimum number of individuals (MNI) analyses revealed
      that at least 68 individuals. All individuals found turned out to have been males
      aged between 20 and 30 years, except for one female associated with a female
      slave gravestone, and one male aged 45-55 years, had been buried in this area of
      the cemetery. The male mean body height was 168 cm (S.D.=5 cm), which lies inside
      the normal range of height for Roman populations at those times. Eleven (16% of
      MNI) individuals exhibit a total of 16 well-healed antemortal cranial traumata.
      Five of the 11 individuals showed multiple trauma. Ten (15% of MNI) individuals
      exhibited a total of 10 perimortal cranial traumata. This is a surprisingly high
      frequency of deadly head injuries, taking into account that most of the gladiator
      types wore helmets. A possible explanation could be the frequently reported
      deathblow technique used by the hammer-carrying death god "Dis Pater". The
      gladiator weaponry is well known through historical sources. At least one injury
      per known type of offensive weapon could be identified, as well as evidence for
      the most popular, the gladiator trident, which was found to be represented by one
      perimortem and two antemortem injuries. Overall the reportedly very strict nature
      of combat rules for gladiator fights could be confirmed by the absence of
      multiple perimortal traumatized individuals, showing a lack of the excessive
      violence commonly observed on medieval battle ground victims. This graveyard
      gives the opportunity to confirm historical aspects and to check the reliability
      of forensic methods for identification of antemortem, perimortem, or postmortem
      bone lesions. Typical examples for these kinds of lesions and injuries are
      presented. The colour of the margins of the traumata proved to be the most
      distinguishing feature for postmortal lesions.

PMID- 16289902
TI  - 26-Locus Y-STR typing in a Bhutanese population sample.
AB  - 26 Y chromosome short tandem repeat (STR) loci were amplified in a sample of 856
      unrelated males from Bhutan, using two multiplex polymerase chain reaction (PCR)
      assays. The first multiplex is the Y-STR 20plex described by Butler et al. [J.M.
      Butler, R. Schoske, P.M. Vallone, M.C. Kline, A.J. Redd, M.F. Hammer, A novel
      multiplex for simultaneous amplification of 20 Y chromosome STR markers, Forensic
      Sci. Int. 129 (2002) 10-24], and the second is a novel (but overlapping) 14plex
      that targets six additional Y-STRs (DYS425, DYS434, DYS435, DYS436, DYS461,
      DYS462) and also amplifies the amelogenin locus. The 26-loci give a
      discriminating power of 0.9957, though even at this resolution one haplotype
      occurs 24 times. We identify novel alleles at five loci and microvariants at a
      further three, which were characterised by sequencing. Extended (11-locus)
      haplotypes for these samples have been submitted to the Y-STR Haplotype Reference
      Database (YHRD).

PMID- 16289901
TI  - Morphological observation of puparia of Chrysomya nigripes (Diptera:
      Calliphoridae) from human corpse.
AB  - This article presents Chrysomya nigripes Aubertin as a blow fly species of
      forensic importance in Thailand, and morphological observation of fly puparia
      using scanning electron microscopy (SEM). Morphologically, we focused on the
      characteristics of puparia used to accurately identify fly species. Numerous
      puparia of C. nigripes were found aggregated, adhering side by side, on the tibia
      of a skeletonized corpse, which was recovered from a forested area of Chiang Mai,
      northern Thailand. In the triangular shape of the anterior end of the puparia,
      three thoracic segments and broad hairy patches beginning dorsolaterally at the
      sixth segments were distinguishing characteristics. This study, showing
      pupariation of the flies along the bone of a corpse as well as morphological
      features, provides important guidance in identifying C. nigripes puparia. A key
      to differentiate puparia of C. nigripes from the other flies of forensic
      importance in Thailand is given.

PMID- 16289903
TI  - Increasing incidence of mumps in Scotland: options for reducing transmission.
AB  - BACKGROUND: There has been a dramatic increase in mumps in Scotland since
      November 2003, with cases primarily in adolescents and young adults. OBJECTIVES:
      This paper describes mumps epidemiology in Scotland, undertakes a risk assessment
      and considers option for reducing transmission. RESULTS: Mumps is primarily a
      risk for the 13-25 year age group, as they have neither been offered two routine
      doses of measles, mumps and rubella MMR vaccine, nor been exposed to wild virus.
      Transmission is facilitated by a high degree of social mixing, with enclosed
      settings (school, universities etc.) being higher risk. On the basis of
      susceptibility and risk of transmission, three categories of higher (17-20
      years), intermediate (21-22; 15-16 years), and low (23-25; 13-14 years) risk were
      defined, all in higher risk enclosed settings. Herd immunity would be very
      difficult to achieve, as it would require unrealistically high MMR uptake (an
      additional 45-80% in 17-20 year olds). A risk management strategy of reducing
      transmission and decreasing the likelihood of outbreaks was therefore proposed.
      Action would be targeted at the higher risk group (17-20 years) in higher risk
      settings. Three options were considered: do nothing; opportunistic immunisation
      through GPs; a mass campaign. The 'do nothing' option was discounted. The
      preferred option was to alert GPs to the need to offer MMR vaccine to 17-20 year
      olds in higher risk settings. The rationale for this was that it had the lowest
      cost, avoided disruption to services, and primarily that it would reduce the
      probability of mumps transmission in higher risk settings. CONCLUSIONS: The Chief
      Medical Officer issued a letter to all health professionals in Scotland
      encouraging them to offer MMR vaccine to 13-15 year olds, who had not previously
      received two doses, and particularly those aged 17-20 years in higher risk
      settings.

PMID- 16289904
TI  - Toremifene: an evaluation of its safety profile.
AB  - Toremifene has been in clinical use for 8 years for the treatment of advanced
      hormone-sensitive breast cancer and the adjuvant treatment of early breast
      cancer. More than 350,000 patient treatment years have accumulated, sufficient to
      allow evaluation of its longer-term safety profile in comparison with tamoxifen
      and, where possible, with raloxifene and aromatase inhibitors. We reviewed all
      preclinical and clinical safety data from 1978 to 2004 and comparative clinical
      safety data between October 1995 and the end of 2004. Secondary endometrial
      cancer incidence was lower with toremifene than with tamoxifen and was similar to
      that with raloxifene. It is speculated that toremifene may unmask existing
      endometrial tumors rather than induce new events. The risk of stroke, pulmonary
      embolism, and cataract may be lower with toremifene than with tamoxifen and the
      risk of pulmonary embolism and deep vein thrombosis lower than with raloxifene.
      Beneficial estrogen agonistic effects were equivalent to those of tamoxifen
      regarding bone mineral density and superior regarding lipid profiles.

PMID- 16289905
TI  - Solitary breast mass as initial presentation of clinically silent metastatic
      renal cell carcinoma.
AB  - Metastasis to the breast from extramammary tumors is rare. Breast metastases of
      renal cell carcinoma (RCC) origin have been described in sporadic case reports.
      We present a patient with a solitary breast mass representing the manifestation
      of clinically silent, metastatic RCC. A 76-year-old female was 12 years prior
      removed from radical nephrectomy for localized RCC. Her new breast mass was
      identified on physical examination. Pathology of the resected mass was diagnostic
      of metastatic RCC and subsequent imaging studies demonstrated a 1.9 cm renal mass
      in her solitary kidney. The patient elected subcutaneous Interleukin-2
      immunotherapy as primary treatment for her recurrent RCC.

PMID- 16289907
TI  - Optimization of dose distribution for HDR brachytherapy of the prostate using
      Attraction-Repulsion Model.
AB  - PURPOSE: To optimize dose distribution for high-dose-rate brachytherapy for
      prostate cancer, we have developed a new algorithm named Attraction-Repulsion
      Model (ARM). In this study, we compared the ARM with geometric optimization (GO).
      METHODS AND MATERIALS: The ARM was used to optimize the dose distribution by
      finding the best dwell time combination. ARM requires grids inside the clinical
      target volume (CTV) and critical organs. These grids generate attraction or
      repulsion based on specific dose constraints. After calculations were performed
      repeatedly until the attraction and repulsion forces reached equilibrium, the
      optimal dwell time distribution was established. We compared the ARM with GO for
      10 patients using dose-volume histograms. RESULTS: The CTV ranged from 23 to 48
      cc, and the CTV V150 ranged from 52% to 79%, and 23% to 44% for GO and ARM,
      respectively. This indicates that the dose homogeneity indices, as well as the
      conformal indices, were higher for ARM than for GO. The urethra V150 was 0-99%
      and 0-1% for GO and ARM, respectively. CONCLUSION: The ARM proved to be superior
      to GO in minimizing the dose to normal structures and in improving dose
      homogeneity for the target while reducing the dose to normal tissues.

PMID- 16289906
TI  - A phase II study of external beam radiotherapy combined with permanent source
      brachytherapy for intermediate-risk, clinically localized adenocarcinoma of the
      prostate: preliminary results of RTOG P-0019.
AB  - PURPOSE: To estimate the rate of acute and late Grade 3-5 genitourinary and
      gastrointestinal toxicity after treatment with external beam radiotherapy and
      permanent source brachytherapy in a multi-institutional, cooperative group
      setting. METHODS AND MATERIALS: All patients were treated with external beam
      radiotherapy (45 Gy in 25 fractions), followed 2-6 weeks later by an interstitial
      implant using 125I to deliver an additional 108 Gy. Late genitourinary toxicity
      was graded according to the Common Toxicity Criteria Version 2.0, and the
      Radiation Therapy Oncology Group/European Organization for Research and Treatment
      of Cancer late radiation morbidity scoring system was used for all other
      toxicity. RESULTS: A total of 138 patients from 28 institutions were entered on
      this study. Acute toxicity information was available in 131 patients, and 127
      patients were analyzable for late toxicity. Acute Grade 3 toxicity was documented
      in 10 of 131 patients (7.6%). No Grade 4 or 5 acute toxicity has been observed.
      The 18-month month estimate of late Grade 3 genitourinary and gastrointestinal
      toxicity was 3.3% (95% confidence interval, 0.1-6.5). No late Grade 4 or 5
      toxicity has been observed. CONCLUSIONS: The acute and late morbidity observed in
      this multi-institutional, cooperative group study is consistent with previous
      reports from single institutions with significant prostate brachytherapy
      experience.

PMID- 16289908
TI  - Association of cisplatin and intra-arterial injection of 131I-lipiodol in
      treatment of hepatocellular carcinoma: results of phase II trial.
AB  - PURPOSE: Intra-arterial injections of 131I-lipiodol (131I-Lip) provide an
      effective treatment for hepatocellular carcinoma. In hepatocellular carcinoma
      cell cultures, concurrent administration of cisplatin increases the cytotoxicity
      of 131I. The efficacy and tolerance of intra-arterial injections of 131I-Lip
      combined with systemic cisplatin was tested in a phase II trial. METHODS AND
      MATERIALS: The inclusion criteria were proven unresectable nonmetastatic
      hepatocellular carcinoma, compensated liver disease, and adequate laboratory test
      findings. Treatment comprised the combination of intra-arterial injection of 131I
      Lip (2.2 GBq) with intravenous infusion of low-dose cisplatin. The combined
      treatment could be repeated. RESULTS: A total of 41 patients were included; 37
      had cirrhosis and 38 had measurable tumors. One to four treatments (median, two)
      were given. The cisplatin dose was 75 mg for the first course and 72 mg for the
      second. Grade 3-4 (n/n) adverse effects were observed in 14 patients,
      polymorphonuclear leukocytes (3/0), platelets (5/1), asthenia (1/0), pain (1/0),
      and vomiting (1/0). Four patients developed pulmonary toxicity; 2 cases were
      likely related to 131I-Lip administration and 1 was fatal. The response rate was
      47% (18 of 38), and the 1- and 2-year survival rate was 73% +/- 7% and 48% +/-
      9%, respectively. CONCLUSION: This combination had a tolerable toxicity profile
      and provided an objective response rate, warranting a phase III trial.

PMID- 16289909
TI  - Intermittent androgen ablation in patients with biochemical failure after pelvic
      radiotherapy for localized prostate cancer.
AB  - PURPOSE: To assess the efficacy of intermittent androgen ablation (IAA) in
      patients with biochemical failure after radiotherapy for prostate cancer. METHODS
      AND MATERIALS: Thirty-nine patients received a luteinizing hormone-releasing
      hormone analog every 2 months for a total of 4 doses. IAA was then discontinued
      if serum prostate-specific antigen (PSA) fell to a normal level with a castrate
      level of testosterone. Therapy was restarted when the serum PSA level reached >
      or = 10 ng/mL and was discontinued if hormone resistance or unacceptable toxicity
      occurred. RESULTS: Median PSA was 9.1 ng/mL at the time of first IAA. The median
      time between the first and the second cycles was 20.1 months, decreasing to 15.5
      months between the third and fourth cycles. Two patients discontinued the
      treatment because of severe hot flushes. Four patients developed hormone
      resistance. With a median follow-up of 56.4 months, 5-year survival is 92.3%.
      Three patients died of unrelated causes. The incidence of distant metastasis is
      6.8%. CONCLUSIONS: The use of IAA seems to be a safe and effective treatment for
      patients with biochemical failure post radiotherapy and no evidence of metastatic
      disease. The use of IAA limits hormone-related side effects and health care costs
      without an apparent increase in the risk for the development of metastatic
      disease.

PMID- 16289910
TI  - A comparison of oral and intravenous pimonidazole in canine tumors using
      intravenous CCI-103F as a control hypoxia marker.
AB  - PURPOSE: Pimonidazole HCl is widely used in immunohistochemical analyses of
      hypoxia in normal and malignant tissues. The present study investigates oral
      administration as a means of minimizing invasiveness. METHODS AND MATERIALS:
      Twelve dogs with confirmed malignancy received 0.5 g/m2 of pimonidazole HCl: 6 by
      mouth and 6 by i.v. infusion. All dogs received i.v. CCI-103F as a control.
      Plasma levels of pimonidazole, pimonidazole N-oxide, and CCI-103F were measured.
      Tumor biopsies were formalin fixed, paraffin embedded, sectioned, immunostained,
      and analyzed for pimonidazole and CCI-103F binding. pH dependence for
      pimonidazole and CCI-103F binding was studied in vitro. RESULTS: Pimonidazole and
      CCI-103F binding in carcinomas and sarcomas was strongly correlated for both oral
      and i.v. pimonidazole HCl (r2=0.97). On average, the extent of pimonidazole
      binding exceeded that for CCI-103F by a factor of approximately 1.2, with the
      factor ranging from 1.0 to 1.65. Binding of both markers was pH dependent, but
      pimonidazole binding was greater at all values of pH. CONCLUSIONS: Oral
      pimonidazole HCl is effective as a hypoxia marker in spontaneously arising canine
      tumors. Selective cellular uptake and concomitant higher levels of binding in
      regions of hypoxia at the high end of pH gradients might account for the greater
      extent of pimonidazole binding.

PMID- 16289912
TI  - Simultaneous beam geometry and intensity map optimization in intensity-modulated
      radiation therapy.
AB  - PURPOSE: In current intensity-modulated radiation therapy (IMRT) plan
      optimization, the focus is on either finding optimal beam angles (or other beam
      delivery parameters such as field segments, couch angles, gantry angles) or
      optimal beam intensities. In this article we offer a mixed integer programming
      (MIP) approach for simultaneously determining an optimal intensity map and
      optimal beam angles for IMRT delivery. Using this approach, we pursue an
      experimental study designed to (a) gauge differences in plan quality metrics with
      respect to different tumor sites and different MIP treatment planning models, and
      (b) test the concept of critical-normal-tissue-ring--a tissue ring of 5 mm
      thickness drawn around the planning target volume (PTV)--and its use for
      designing conformal plans. METHODS AND MATERIALS: Our treatment planning models
      use two classes of decision variables to capture the beam configuration and
      intensities simultaneously. Binary (0/1) variables are used to capture "on" or
      "off" or "yes" or "no" decisions for each field, and nonnegative continuous
      variables are used to represent intensities of beamlets. Binary and continuous
      variables are also used for each voxel to capture dose level and dose deviation
      from target bounds. Treatment planning models were designed to explicitly
      incorporate the following planning constraints: (a) upper/lower/mean dose-based
      constraints, (b) dose-volume and equivalent-uniform-dose (EUD) constraints for
      critical structures, (c) homogeneity constraints (underdose/overdose) for PTV,
      (d) coverage constraints for PTV, and (e) maximum number of beams allowed. Within
      this constrained solution space, five optimization strategies involving clinical
      objectives were analyzed: optimize total intensity to PTV, optimize total
      intensity and then optimize conformity, optimize total intensity and then
      optimize homogeneity, minimize total dose to critical structures, minimize total
      dose to critical structures and optimize conformity simultaneously. We emphasize
      that the objectives that include optimizing conformity make use of the critical
      normal-tissue-ring. Three tumor sites: head-and-neck, pediatric brain, and
      prostate are used for comparison. RESULTS: The critical-normal-tissue-ring acts
      as a good device for enforcing conformity. Trends in the characteristics and
      quality of plans resulting from each model were observed. Attempts to reduce dose
      to critical structures tend to worsen PTV conformity (1.542 to 3.092) and
      homogeneity (1.223 to 1.984), depending on the relative size and spatial distance
      of the critical structures to the PTV. When the critical structures are
      relatively small compared with the PTV (as in the case for the pediatric brain
      tumor, where each is less than 15% in volume), dose reduction to critical
      structures is accompanied by much worse scores in conformity (2.482) and
      homogeneity (1.984). When the critical structures are larger, as in the case of
      head-and-neck (approximately 50%), the conformity and homogeneity deterioration
      is less significant (1.542 and 1.239, respectively). There is a clear tradeoff
      between homogeneity, conformity, and minimum dose to organs at risk (OARs). For
      head-and-neck and pediatric brain tumor, the model that minimizes total dose to
      critical structures and optimizes conformity simultaneously offers a compromise
      among these factors, resulting in reduced critical structure dose with conformal
      and homogeneous plans. In the prostate case, the tumor is smaller than the two
      large nearby critical structures, and all models provide very homogeneous PTV
      dose distribution. However, minimizing dose to critical structures worsens
      conformity, as it spreads the radiation to the area surrounding the PTV. The
      maximum dose to the critical structures also increases slightly. Compared with
      plans used in the clinic which generally have uniformly spaced beam angles, the
      optimal clinically acceptable plans obtained via the methods herein do not have
      equispaced beams. The optimal beam angles returned appear to be nonintuitive, and
      depend on PTV size and geometry and the spatial relationship between the tumor
      and critical structures. CONCLUSIONS: The MIP model described allows simultaneous
      optimization over the space of beamlet fluence weights and beam and couch angles.
      Based on experiments with tumor data, this approach can return good plans that
      are clinically acceptable and practical. This work distinguishes itself from
      recent IMRT research in several ways. First, in previous methods beam angles are
      selected before intensity map optimization. Herein, we employ 0/1 variables to
      model the set of candidate beams, and thereby allow the optimization process
      itself to select optimal beams. Second, instead of incorporating dose-volume
      criteria within the objective function as in previous work, herein, a combination
      of discrete and continuous variables associated with each voxel provides a
      mechanism to strictly enforce dose-volume criteria within the constraints. Third,
      using the construct of critical-normal-tissue-ring within the objective function
      can enhance the achievement of conformal plans. Based on the three tumor sites
      considered, it appears that volume and spatial geometry with respect to the PTV
      are important factors to consider when selecting objectives to optimize, and in
      estimating how well suited a particular model is for achieving a specified goal.

PMID- 16289911
TI  - Low-grade toxicity after conformal radiation therapy for prostate cancer--impact
      of bladder volume.
AB  - PURPOSE: To assess the impact of dose-volume histogram parameters on low-grade
      toxicity after radiotherapy for prostate cancer. METHODS AND MATERIALS: Eighty
      patients have been surveyed prospectively before (time A), at the last day (B), 2
      months after (C), and 16 months (median) after (D) radiotherapy (70.2 Gy) using a
      validated questionnaire (Expanded Prostate Cancer Index Composite). Dose-volume
      histograms were correlated with urinary and bowel function/bother scores.
      RESULTS: The initial bladder volume and the percentage of the bladder volume
      receiving 10%-90% of the prescription dose significantly correlated with urinary
      function/bother scores (significant cutoff levels found for all dose levels).
      Pain with urination proved to be mainly an acute problem, subsiding faster for
      patients with larger bladder volumes and smaller volumes inside particular
      isodose lines. At time D, persisting problems with smaller initial bladder
      volumes were a weak stream and an increased frequency of urination. Though
      bladder volume and planning target volume both independently have an influence on
      dose-volume histogram parameters for the bladder, bladder volume plays the
      decisive role for urinary toxicity. CONCLUSIONS: The patient's ability to fill
      the bladder has a major impact on the dose-volume histogram and both acute and
      late urinary toxicity.

PMID- 16289913
TI  - Expression and purification of the subunits of human translational initiation
      factor 2 (eIF2): phosphorylation of eIF2 alpha and beta.
AB  - Eukaryotic initiation factor 2 (eIF2) is a GDP-binding protein with three
      subunits: alpha, beta, and gamma. It delivers initiator tRNA (Met-tRNAi) to 40S
      ribosomes in a GTP-dependent manner. The factor regulates the translation of
      messenger RNAs through the phosphorylation of serine 51 residue in the small or
      alpha-subunit of eIF2 (eIF2alpha) and modulation of its interaction with a rate
      limiting heteropentameric protein eIF2B. To understand the structural,
      functional, and regulatory roles of each of these subunits in the various
      activities of phosphorylated and unphosphorylated eIF2, such, as its ability to
      interact with GTP, Met-tRNAi, 40S ribosomes and with various proteins, we have
      for the first time over expressed all the three subunits of human eIF2
      independently, and, also together in Sf9 cells using pFast Bac HT vector of
      baculovirus expression system. The expression of all subunits increased with
      increase in infection time up to 72 h. We have also over expressed three mutant
      forms of eIF2alpha viz, S51A, S51D, and S48A in which the serine at 51 or 48
      position is replaced by an alanine or aspartic acid with 6x histidine tag at the
      N-terminus. Further, any of the two subunits or all the three subunits of eIF2
      were coexpressed by multiple infection of cells with recombinant viruses.
      Purified alpha (wt and mutants) and beta subunits were found suitable to serve as
      substrates for different kinases. The recombinant subunits of eIF2alpha and beta
      subunits were also phosphorylated in cultured insect cells. Phosphorylation of
      eIF2alpha in vitro was not significantly different in the presence and absence of
      the other subunits.

PMID- 16289914
TI  - Expression and characterization of human vascular endothelial growth factor
      (VEGF165) in insect cells.
AB  - Vascular endothelial growth factor (VEGF) is the best characterized
      multifunctional protein which plays a key role in normal and pathologic
      angiogenesis. The gene encoding the human VEGF165 was cloned from the ovarian
      carcinoma cell line (OVCAR3) and expressed in insect cells using the baculovirus
      expression vector system. The recombinant human VEGF165 (rhVEGF165) protein
      produced by Sf21 (Spodoptera frugiperda) cells underwent a similar processing
      compared with mammalian cells, including efficient glycosylation, formation of a
      disulfide-linked dimer and secretion into the media. The rhVEGF165 had a high
      affinity for heparin and this characteristic was used to purify this form to
      homogeneity by heparin affinity, Resource S and Resource RPC columns. The
      biological activity of the purified 42-kDa homodimer was shown by the induction
      of the proliferation of human umbilical vein derived endothelial cells. These
      results demonstrate that an angiogenic growth factor whose normal processing
      requires glycosylation and disulfide-bridge formation can be efficiently
      expressed in high concentration (up to 20mg/L) in Sf21 cells.

PMID- 16289915
TI  - An improved expression plasmid for affinity purification of Staphylococcus aureus
      gyrase A subunit.
AB  - Of the bacterial topoisomerases, the gyrase A subunit (GyrA) of Staphylococcus
      aureus is particularly difficult to purify because of its tendency to form
      inclusion bodies. Previous attempts at purification yielded low concentrations of
      protein with reduced specific activity. To overcome this problem, we modified the
      commercially available plasmid expression vector, pBAD/Thio-TOPO, via the
      addition of DNA sequences encoding a hexahistidine tag upstream and a cleavage
      site for tobacco etch virus protease downstream of the gene encoding thioredoxin.
      The resulting expression system consisting of the modified plasmid, pSAGA7, and
      the recommended host strain, Escherichia coli TOP 10, facilitated high level
      expression of soluble GyrA and its affinity purification to over 95% homogeneity.
      Purified GyrA had high biological activity as evidenced by a specific activity of
      4.3x10(5)U/mg. The pSAGA7/TOP10 expression system also facilitated the expression
      and purification of a subunit of S. aureus topoisomerase IV, ParE, and a recently
      discovered protein unrelated to topoisomerases, QnrB, two "hard to purify"
      proteins. We conclude that pSAGA7 might be useful for high-level soluble
      expression and purification of diverse microbial proteins.

PMID- 16289916
TI  - Novel protein purification system utilizing an N-terminal fusion protein and a
      caspase-3 cleavable linker.
AB  - Coupled with over-expression in host organisms, fusion protein systems afford
      economical methods to obtain large quantities of target proteins in a fast and
      efficient manner. Some proteases used for these purposes cleave C-terminal to
      their recognition sequences and do not leave extra amino acids on the target.
      However, they are often inefficient and are frequently promiscuous, resulting in
      non-specific cleavages of the target protein. To address these issues, we created
      a fusion protein system that utilizes a highly efficient enzyme and leaves no
      residual amino acids on the target protein after removal of the affinity tag. We
      designed a glutathione S-transferase (GST)-fusion protein vector with a caspase-3
      consensus cleavage sequence located between the N-terminal GST tag and a target
      protein. We show that the enzyme efficiently cleaves the fusion protein without
      leaving excess amino acids on the target protein. In addition, we used an
      engineered caspase-3 enzyme that is highly stable, has increased activity
      relative to the wild-type enzyme, and contains a poly-histidine tag that allows
      for efficient removal of the enzyme after cleavage of the fusion protein.
      Although we have developed this system using a GST tag, the system is amenable to
      any commercially available affinity tag.

PMID- 16289917
TI  - Purification and characterization of exo-beta-D-glucosaminidase from Aspergillus
      fumigatus S-26.
AB  - An extracellular 104 kDa exo-beta-d-glucosaminidase was purified and
      characterized from the culture supernatant of Aspergillus fumigatus S-26, which
      showed exceptionally strong chitosanolytic enzyme activity. The purified enzyme
      showed optimum pH of 3.0-6.0 and optimum temperature of 50-60 degrees C, and was
      stable between pH 2.0 and 10.0 and under 35 degrees C. The Km, Vmax, and kcat
      were determined to be 1.0 mg chitosan/ml, 7.8x10(-8) mol/s/mg protein, and 28.3 s
      1, respectively. The exo-beta-D-glucosaminidase was severely inactivated by Cu2+
      and Hg2+ at 10 mM. 2-Hydroxy-5-nitrobenzyl bromide, N-bromosuccinimide, and p
      chloromercuribenzoic acid inhibited the enzyme. The enzyme did not degrade
      chitin, cellulose, and starch. The exo-beta-D-glucosaminidase did not reduce the
      viscosity of chitosan solutions at early stage of reaction, suggesting the exo
      type of cleavage in polymeric chitosan chains. The exo-beta-D-glucosaminidase
      liberated only GlcN from chitosan, and GlcN plus the one-residue shortened
      oligomers from (GlcN)2-7. The exo-beta-D-glucosaminidase exhibited
      transglycosylation activity, resulting in the one-residue elongated oligomers.

PMID- 16289918
TI  - Maize uroporphyrinogen III methyltransferase: overexpression of the functional
      gene fragments in Escherichia coli and one-step purification.
AB  - S-Adenosyl-L-methionine: uroporphyrinogen III methyltransferase (SUMT), a key
      regulatory enzyme, converts uroporphyrinogen III to precorrin-2 in the
      porphinoids biosynthesis. In this study, the mature SUMT was signified that the
      maize SUMT precursor encoded by the open reading frame of maize SUMT cDNA was
      deleted the first 91 amino acids constituting the postulated signal peptide.
      Several mature SUMT fusion and deletion mutants were conducted. It actively
      expressed in Escherichia coli that the mature SUMT, or the truncated one deleting
      the C-terminal extra 52 amino acids based on SUMT sequence comparisons. On the
      contrary, it expressed as an inclusion body in E. coli that the mature SUMT
      fusion mutant, the SUMT precursor, or the mature SUMT deleting the N-terminal 36
      amino acids including glycine-rich region involved directly in SAM binding. The
      purified His6-tagged mature SUMT was homodimer with a molecular weight of 34 kDa,
      as shown by SDS-PAGE, 52 kDa using gel-filtration chromatography, and 79 kDa by
      dynamic light scattering assay. Red fluorescent compounds were associated with
      the recombinant mature SUMT which were identified as sirohydrochlorin and
      trimethylpyrrocorphin by spectroscopic analysis. This association slightly
      altered the protein secondary structure confirmed by circular dichroism assay.

PMID- 16289919
TI  - Prokaryotic expression, purification, and polyclonal antibody production against
      a novel drug resistance gene of Leishmania donovani clinical isolate.
AB  - Diseases produced by protozoan parasites are one of the main causes of morbidity
      and mortality around the world, affecting millions of people. Among these,
      leishmaniasis has become the second most common cause of death and the problem is
      further complicated by the expansion of parasite resistance to the conventional
      drugs. The high rate of therapeutic failure thus calls for new rational
      approaches to develop alternative drugs. Understanding resistance mechanisms may
      help identify new targets for drug development. So we present here the cloning,
      expression, purification, and antibody production of a gene implicated in
      imparting resistance to pentavalent antimony (SbV) in clinical isolates of kala
      azar with a view to gain insight into the novel mechanism of its drug resistance.

PMID- 16289920
TI  - A rare cause of parotid swelling: primary hydatid cyst.
AB  - Hydatid disease is a zoonotic infection caused by Echinococcus species. Cystic
      form of this infection mostly involves liver and lung. Hydatid disease of the
      parotid gland is a very rare entity that may be easily overlooked in daily
      practice. On the other hand, rupture of the cyst during surgery may give rise to
      serious complications. We present a case of hydatid cyst of the parotid and
      discuss the differential diagnosis of this rare condition.

PMID- 16289921
TI  - Description of unexplained chest pain and its influence on daily life in men and
      women.
AB  - BACKGROUND: Patients with unexplained chest pain have seldom organic pathology.
      Although both physical and psychological factors have been studied and suggested
      as causes of chest pain. AIM: The aim was to describe the experience of
      unexplained chest pain and its influence on daily life situation in men and
      women. METHODS: Nine women and eleven men with unexplained chest pain, aged 31-62
      years were interviewed. A qualitative descriptive design was used. The interviews
      were analyzed by content analysis focusing on experience by gender. RESULTS: The
      results embraced two domains descriptions and consequences of chest pain and
      daily life situation. Words like pressure, cramp, strong, or burning were used in
      the descriptions of the chest pain experienced with more similarities than
      variations between men and women. Physical, psychological and social consequences
      due to chest pain influenced daily life. The men specifically reported having a
      'fast tempo' in their lives, with stress at work being seen as a feature
      experienced by both men and women. CONCLUSIONS: This study shows that men and
      women had more similarities than variations in descriptions of chest pain. Their
      unexplained chest pain influenced their functions in daily life that led to,
      especially for the men, few contacts outside the family and therefore a weak
      social network.

PMID- 16289922
TI  - Evidence for a link between changes to gaze behaviour and risk of falling in
      older adults during adaptive locomotion.
AB  - There is increasing evidence that gaze stabilization with respect to footfall
      targets plays a crucial role in the control of visually guided stepping and that
      there are significant changes to gaze behaviour as we age. However, past research
      has not measured if age-related changes in gaze behaviour are associated with
      changes to stepping performance. This paper aims to identify differences in gaze
      behaviour between young (n=8) adults, older adults determined to be at a low-risk
      of falling (low-risk, n=4) and older adults prone to falling (high-risk, n=4)
      performing an adaptive locomotor task and attempts to relate observed differences
      in gaze behaviour to decline in stepping performance. Participants walked at a
      self-selected pace along a 9m pathway stepping into two footfall target locations
      en route. Gaze behaviour and lower limb kinematics were recorded using an ASL 500
      gaze tracker interfaced with a Vicon motion analysis system. Results showed that
      older adults looked significantly sooner to targets, and fixated the targets for
      longer, than younger adults. There were also significant differences in these
      measures between high and low-risk older adults. On average, high-risk older
      adults looked away from targets significantly sooner and demonstrated less
      accurate and more variable foot placements than younger adults and low-risk older
      adults. These findings suggest that, as we age, we need more time to plan precise
      stepping movements and clearly demonstrate that there are differences between low
      risk and high-risk older adults in both where and when they look at future
      stepping targets and the precision with which they subsequently step. We propose
      that high-risk older adults may prioritize the planning of future actions over
      the accurate execution of ongoing movements and that adoption of this strategy
      may contribute to an increased likelihood of falls.

PMID- 16289923
TI  - TNF-alpha-induced apoptosis in human naive and memory CD8+ T cells in aged
      humans.
AB  - Recently, human CD8+ T cells have been divided into naive, central memory
      (T(CM)), and two types of effector memory cells (T(EM) and T(EMRA)), which are
      phenotypically identified by a set of cell surface molecules. In this
      investigation, we have compared the relative sensitivity of these subsets to TNF
      alpha-induced apoptosis in young and aged humans. Our data show increased
      sensitivity of naive and T(CM) CD8+ T cells from aged humans to TNF-alpha-induced
      apoptosis as compared to young subjects. Both T(EM) and T(EMRA) CD8+ T cells from
      young and aged subjects were relatively resistant to TNF-alpha-induced apoptosis
      and no significant difference was observed between young and aged subjects.
      Increased apoptosis of naive and T(CM) CD8+ T cells in aged humans was associated
      with increased activation of caspase-8 and caspase-3 as compared to young
      subjects. There was no difference in the expression of TNFR-I or TNFR-II on any
      of the four subpopulations of CD8+ T cells between young and aged subjects. These
      data suggest that increased TNF-alpha-induced apoptosis of naive and T(CM) CD8+ T
      cells may play a role in the deficiency of naive and T(CM) CD8+ T cells in human
      aging. However, apoptosis does not appear to play a major role in increased
      accumulation of effector memory CD8+ T cells during human aging.

PMID- 16289924
TI  - Aging affect the anti-tumor potential of dendritic cell vaccination, but it can
      be overcome by co-stimulation with anti-OX40 or anti-4-1BB.
AB  - It has been well established that there is a decline in immune function with age
      resulting in a diminished capacity to respond to infections or tumors. Although
      many studies have demonstrated the efficacy of autologous dendritic cells (DC)
      vaccines in stimulating an anti-tumor immune response in the young, almost none
      of these reports consider the effect that aging has on the immune system or test
      whether DC-vaccination is effective in old hosts. In this study we compared the
      efficacy of DC-vaccination in young and old mice. Our results showed that DC
      vaccination in young animals induced an anti-tumor response resulting in
      approximately 60% tumor growth inhibition, while minimal protection was observed
      in old animals. DC vaccination plus rIL-2 further enhanced the anti-tumor
      response in young animals (approximately 70-75% inhibition), while ineffective in
      old animals. In contrast, co-administration of anti-OX-40 or anti-4-1BB mAbs
      vigorously enhanced the anti-tumor immune response in both young (approximately
      85-90% inhibition) and old mice (approximately 70-75% inhibition). Our data
      indicate that although old mice have a decline in immune function, they have the
      capacity to develop strong anti-tumor responses as long as they are provided with
      efficient co-stimulation.

PMID- 16289925
TI  - Effect of aging on expression of angiogenesis-related factors in mouse skeletal
      muscle.
AB  - The molecular mechanisms by which capillary supply is maintained with advancing
      age remain to be elucidated. To help clarify these mechanisms, we investigated
      the gene expression levels of angiogenesis-related factors in young (2.5-month
      old), adult (6-month-old), and old (22-month-old) mice. To assess the capillary
      supply, the capillary endothelium in frozen transverse sections was identified by
      staining for alkaline phosphatase. The mRNA levels for angiogenesis-related
      factors were analyzed using real-time RT-PCR. The capillary supply to individual
      muscle fibers, assessed as the number of capillaries around a muscle fiber, did
      not change with advancing age. Real-time RT-PCR analysis showed that (1) the
      level of mRNA for VEGF was lower in old animals than young animals; (2) the mRNA
      levels of Flt-1 and neuropilin-1 are lower in old animals than young animals,
      while that of KDR/Flk-1 remained unchanged with advancing age; and (3) the levels
      of mRNA for angiopoietin-1 and -2 remained unchanged, while the mRNA for Tie-2
      was lower in old animals than young animals. These findings suggest that
      capillary supply is maintained irrespective of the down-regulation of several
      angiogenesis-related factors and that old animals possess the minimum levels of
      maintenance and reparative abilities needed to preserve the capillary supply.

PMID- 16289926
TI  - 3-D echocardiographic imaging of double aortic arch.
AB  - Delineation of arch abnormalities is difficult by conventional 2-D
      echocardiography and MRI has been the investigation of choice. 3-D
      echocardiography is increasingly used in congenital heart disease for both
      functional anatomy and morphology. This case report demonstrates that 3-D
      echocardiography can be used in delineating arch anomalies, which can avoid
      further imaging that needs a general anaesthetic.

PMID- 16289927
TI  - Unsolved issues of left ventricular hypertrabeculation/noncompaction.

PMID- 16289928
TI  - Spatial maps in frontal and prefrontal cortex.
AB  - Though the function of prefrontal cortex has been extensively investigated,
      little is known about the internal organization of individual prefrontal areas.
      Functional magnetic resonance imaging was used to show that some frontal and
      prefrontal cortical areas represent visual space in orderly, reproducible,
      topographic maps. The map-containing areas partly overlap dorsolateral prefrontal
      areas engaged by working memory tasks. These maps may be useful for attending to
      task-relevant objects at various spatial locations, an aspect of the executive
      control of attention.

PMID- 16289929
TI  - MRI-based volumetry of head compartments: normative values of healthy adults.
AB  - The size of head compartments (head and brain volume, intracranial volume, gray
      and white matter volume, cerebrospinal fluid volume) and their ratios were
      determined on the basis of magnetic resonance images of the head acquired in a
      reference population of 502 healthy subjects. Age-matched subgroups were selected
      to reveal gender-related differences and changes with age. Normative data are
      provided in the form of simple equations that allow transforming measured
      compartment volumes into z scores, offering the possibility to relate individual
      data to a larger population.

PMID- 16289930
TI  - The Marijuana Ladder: measuring motivation to change marijuana use in
      incarcerated adolescents.
AB  - The purpose of this study was to determine if a modified version of the
      Contemplation Ladder, a measure of motivation to change marijuana use among
      incarcerated adolescents (Marijuana Ladder; ML), was related to marijuana use and
      treatment engagement. Participants (N=122) in this study were all incarcerated at
      a state juvenile correctional facility in the Northeast. Adolescents were
      assessed at the beginning of their incarceration, 2 months into their
      incarceration, and 3 months after their release. There was a significant negative
      relationship between ML scores and marijuana use and a significant positive
      relationship between ML scores and treatment engagement. When controlling for
      prior marijuana use and age, ML scores at baseline significantly added to the
      prediction of marijuana use and treatment engagement among incarcerated
      adolescents. Results support the concurrent validity and the predictive validity
      of the ML. This measure has the potential to provide important information for
      Juvenile Justice Facilities that might aid in treatment planning and discharge
      planning for incarcerated adolescents. In addition, researchers may find a quick
      visual analog measure of motivation to change marijuana use with good
      psychometric properties useful.

PMID- 16289932
TI  - Neurodegenerative disorders mimicking progressive supranuclear palsy: a report of
      three cases.
AB  - Progressive supranuclear palsy (PSP) is rarely confused with other parkinsonian
      disorders once the vertical gaze palsy appears. Corticobasal degeneration is the
      most common differential diagnostic entity. We describe three cases diagnosed
      during life as PSP but found to have another neurologic disorder at autopsy. No
      explanation for the gaze palsies was found in any case.

PMID- 16289931
TI  - Hyperthermia induced by 3,4-methylenedioxymethamphetamine in unrestrained rhesus
      monkeys.
AB  - BACKGROUND: Exposure to (+/-)3,4-methylenedioxymethamphetamine ((+/-)MDMA)
      results in lasting reductions of many markers for serotonin terminals in a range
      of species. In rodents, the severity of insult depends in large part on the
      generation of hyperthermia in the subject. (+/-)MDMA can produce either
      hyperthermia or hypothermia in rodents depending on the ambient temperature and
      these effects may be limited to the S(+) enantiomer. Limited prior evidence
      suggests (+/-)MDMA does not produce hyperthermia in chair-restrained monkeys
      [Bowyer, J.F., Young, J.F., Slikker, W., Itzak, Y., Mayorga, A.J., Newport, G.D.,
      Ali, S.F., Frederick, D.L., Paule, M.G., 2003. Plasma levels of parent compound
      and metabolites after doses of either d-fenfluramine or d-3,4
      methylenedioxymethamphetamine (MDMA) that produce long-term serotonergic
      alterations. Neurotoxicology 24, 379-390]. This study was therefore conducted to
      determine if racemic MDMA and its enantiomers induce hyperthermia and increase
      spontaneous locomotor activity in unrestrained rhesus monkeys. METHODS: Body
      temperature and spontaneous home cage activity were monitored continuously in
      four monkeys via radiotelemetric devices. The subjects were challenged with 1.7
      mg/kg, i.m., (+/-)MDMA, S(+)MDMA and R(-)MDMA in pseudorandomized order. RESULTS:
      Maximum and average temperature in the 4h interval post-dosing was elevated 0.7
      0.9 degrees C by (+/-)MDMA and each enantiomer. Reductions in locomotor activity
      following dosing did not reliably differ from vehicle effects. CONCLUSIONS: MDMA
      produces an acute hyperthermia in unrestrained rhesus monkeys, much as it does
      with rats, mice, pigs, rabbits and humans. Hyperthermia occurs despite no
      increase in locomotor activity thus the effect does not depend on motor
      activation. Each enantiomer appears to be equivalently active thus primates may
      differ from rodents in thermoregulatory sensitivity to the R(-) enantiomer.
      Significant differences in outcome between this and a prior study in monkeys
      indicate a need for additional study of the thermoregulatory impact of MDMA in
      nonhuman primates.

PMID- 16289934
TI  - A novel fingerprint map for detecting SARS-CoV.
AB  - Spike (S) protein is the most important membrane protein on the surface of severe
      acute respiratory syndrome coronavirus (SARS-CoV). It associates with cellular
      receptors to mediate infection of their target cells. Inspired by such a
      mechanism, an in-depth investigation into the genome sequences of S protein of
      SARS-CoV and its receptor are conducted thru a mathematical transformation and
      graphic approach. As an outcome, a novel method for visualizing the
      characteristic of SARS-CoV is suggested. An extensive comparison among a large
      number of genome sequences has proved that the characteristic thus revealed is
      unique for SARS-CoV. As such, the characteristic can be regarded as the
      fingerprint map of SARS-CoV for diagnostic usage. Moreover, the conclusion has
      been further supported in a real case in Guangdong province of China. The
      fingerprint map proposed here has the merits of clear visibility and reliability
      that can serve as a complementary clinical tool for detecting SARS-CoV,
      particularly for the cases where the results obtained by the conventional methods
      are uncertain or conflicted with each other.

PMID- 16289933
TI  - A monolithic-phase based on-line extraction approach for determination of
      pharmaceutical components in human plasma by HPLC-MS/MS and a comparison with
      liquid-liquid extraction.
AB  - An automated procedure using monolithic-phase based on-line extraction is
      described for pharmaceutical component analysis in plasma by LC-MS/MS. In this
      approach, a short monolithic C(18) 4.6 mm x 10 mm cartridge is used for high flow
      extraction at 4 mL/min. Plasma samples were subjected to protein precipitation
      first with acetonitrile, and the supernatant was diluted and loaded onto a
      monolithic cartridge. Sample elution was accomplished with narrow-bore LC-MS/MS
      system. A method for determination of Amprenavir (APV) and Atazanavir (AZV) in
      human plasma was developed with this approach. After 0.1 mL of plasma was
      transferred into each well of a 96-well plate by a liquid handler, the rest of
      sample preparation time typically only takes about 20 min. A Phenomenex Luna
      C18(2) 2.0 mm x 150 mm analytical column was used for the separation at a flow
      rate of 0.3 mL/min. The run time for each sample was 4 min. The standard curve
      range was 2.77-1520 ng/mL for Atazanavir, and 4.50-2560 ng/mL for Amprenavir. The
      accuracy (%bias) at the lower limit of quantitation (LLOQ) for Atazanavir was
      2.7% and the precision (%CV) at the LLOQ was 7.9%, while the accuracy at LLOQ for
      Amprenavir was -1.3% and the precision at LLOQ was 7.8%. The inter-day %bias and
      %CV of the quality control samples of Atazanavir were < or = 4.5% and < or =
      6.5%, respectively. The inter-day %bias and %CV of the quality control samples of
      Amprenavir were < or = 1.1% and < or = 7.2%, respectively. Coefficients of
      determination, a measure of linearity, ranged from 0.993 to 0.999. Very low carry
      over (0.006%) even after high standard sample was demonstrated in the monolithic
      phase based method. Other characteristics of such method include high recovery
      and good tolerance to matrix effect, which was demonstrated by 12 lots of plasma.
      The back pressure of the monolithic extraction cartridge remained the same after
      450 samples injected. The performance of the monolithic-phased on-line extraction
      method was compared with that done by an automated 96-well liquid-liquid
      extraction procedure, which was carried out using hexane:ethyl acetate as the
      extraction solvent. The results showed that similar precision and accuracy were
      achieved by both methods.

PMID- 16289935
TI  - Hemoglobin S-thiolation during peroxide-induced oxidative stress in chicken
      blood.
AB  - Protein S-thiolation or protein-glutathione mixed disulfide (PSSG) occurs when
      cells are exposed to oxidative stress, and has been implicated in several
      cellular functions. The S-thiolation of hemoglobin as well as other abundant
      proteins is proposed to participate as a redox buffer, being part of the
      antioxidant protection system of the cell during the oxidative challenge. We
      studied the oxidative stress caused by peroxides (H(2)O(2), cumene and tert-butyl
      hydroperoxide) on chicken blood by measuring the thiol/disulfide status. Chicken
      blood under peroxide treatment showed a time- and concentration-dependent
      increase in glutathione disulfide (GSSG) and PSSG. GSSG peaked immediately after
      treatment (1 min), while PSSG increased progressively over time, showing a
      maximum after about 30 min. The system recovered after 140 min of incubation,
      with GSSG and PSSG then barely reaching control values. The S-thiolation of
      hemoglobin was monitored under nondenaturing PAGE, and the fraction of S
      thiolated hemoglobin, or Hb A1, rose in a dose-dependent fashion and was
      proportional to total S-thiolation, measured as PSSG. This significant
      correlation indicates that hemoglobin is the major S-thiolated protein in chicken
      erythrocytes treated with peroxides. The present work shows the behavior of
      chicken blood under peroxide treatment; it anticipated that chicken hemoglobin
      thiol groups can actively participate in the redox processes of erythrocytes
      exposed to oxidative stress, and that hemoglobin is the major S-thiolated
      protein. This further corroborates the hypothesis that abundant proteins, such as
      hemoglobin, may take part in the cellular antioxidant defense system.

PMID- 16289936
TI  - Are hERG channel inhibition and QT interval prolongation all there is in drug
      induced torsadogenesis? A review of emerging trends.
AB  - Contemporary preclinical in vitro and in vivo methods have been imperfect in
      predicting drug-induced Torsades de Pointes (TdP) in humans. A better
      understanding of additional relevant factors in the genesis of drug-induced TdP
      is necessary. New sophisticated in vitro techniques, such as arterially perfused
      ventricular wedge preparations or isolated perfused hearts, potentially offer a
      better understanding of torsadogenic mechanisms and a refinement of drug testing.
      Of particular interest are the dispersion of repolarization and the
      refractoriness of different cell types across the ventricular wall, triangulation
      of the action potential, reverse use dependence and instability of the action
      potential duration. In vivo models are currently refined by establishing
      parameters such as beat-to-beat variability and T-wave morphology as derived from
      the in vitro proarrhythmia indices. Animal models of proarrhythmia are to date
      not recommended for routine evaluation. A pharmacodynamic interaction with
      combinations of torsadogenic compounds is another area to be considered. Little
      is known about channel/receptor cross talk, although considerable evidence exists
      that cardiac G protein-coupled receptors can modulate hERG channel function. More
      investigations are necessary to further evaluate the role of altered gene
      expression, mutations, and polymorphisms in drug-induced TdP. A novel mechanism
      of drug-induced torsadogenesis is the reduced expression of hERG channel protein
      on the plasma membrane due to a trafficking defect. Pharmacokinetic and
      metabolism data are crucial for calculating the risk of a torsadogenic potential
      in man. Consideration of intracardiac accumulation can help in delineating
      pharmacokinetic-pharmacodyamic relationships. In silico virtual screening
      procedures with new chemical entities to predict hERG block may develop as a
      promising tool. The role of in silico modeling of TdP arrhythmia is likely to
      become increasingly important for organizing and integrating the vast amount of
      generated data. At present, however, in silico methods cannot replace existing
      preclinical in vitro and in vivo models.

PMID- 16289937
TI  - Molecular cloning and characterization of the clock gene period2 in the testis of
      lizard Podarcis sicula and its expression during seasonal reproductive cycle.
AB  - Clock genes are known to oscillate with circadian rhythmicity in the central
      clock structure, the suprachiasmatic nucleus of the hypothalamus, and also in
      peripheral tissues. Reproduction is a peripheral activity that is strongly
      influenced by a circadian clock in many organisms. Most mammals that exhibit a
      seasonal cycle are able to decode the daily changes in light across the year and
      to translate these in hormonal signals that regulate reproductive cycles.
      Expression of many clock genes has been revealed in mouse testis, although
      transcription of these genes seems to be constitutive in 24 h, suggesting that
      these genes may play in the testis a different role with regard to the central
      clockwork function. The seasonal breeding lizard Podarcis sicula represents an
      attractive model for studying some developmental and differentiation phenomena,
      such as gonadal maturation, since in the adult male the testis shows a spring
      full activity and a complete summer regression. Experimental data seem to suggest
      that in lizard the environmental factors, as photoperiod and temperature, affect
      the endogenous elements, although the interaction mechanisms are unknown. It is
      known that temperature signals have a direct influence on clock processes such as
      transcription, translation, protein phosphorylation and degradation. In addition,
      most data show that the expression of circadian clock genes, such as period2, is
      affected by length of photoperiod. In this way, the core clockwork may also
      decode seasonal information. Here we report the cloning, sequencing and
      bioinformatic analysis of period2 gene, isolated from the testis of lizard P.
      sicula, and its expression both in the testis and in other tissues during the
      different phases of the seasonal cycle. RT-PCR assays enlighten the presence of
      transcript in testis, brain, heart, liver and kidney in all the phases analysed.
      Moreover, real time quantitative PCR assays detect a peak of per2 testicular
      expression during gonadal regression. Our preliminary results cannot clearly
      demonstrate the involvement of per2 gene in seasonal reproductive cycle of male
      lizard P. sicula, but its presence in the testis may suggest a role of this gene
      during spermatogenesis. Besides, our work can provide numerous starting points to
      clarify the role of per2 during seasonal reproductive cycle.

PMID- 16289938
TI  - Identification of a buried pocket for potent and selective inhibition of Chk1:
      prediction and verification.
AB  - Inhibition of the Chk1 kinase by small molecules binding to its active site is a
      strategy of great therapeutic interest for oncology. We report how computational
      modelling predicted the binding mode of ligands of special interest to the Chk1
      ATP site, for representatives of an indazole series and debromohymenialdisine.
      These binding modes were subsequently confirmed by X-ray crystallography. The
      binding mode of a potent indazole derivative involves non-conventional C-H...O
      and N-H...pi-aromatic interactions with the protein. These interactions are
      formed in a buried pocket at the periphery of the ATP-binding site, the
      importance of which has previously been overlooked for ligand design against
      Chk1. It is demonstrated that filling this pocket can confer ligands with
      dramatically enhanced affinity for Chk1. Structural arguments in conjunction with
      assay data explain why targeting this pocket is also advantageous for selective
      binding to Chk1. Structural overlays of known inhibitors complexed with Chk1 show
      that only the indazole series utilizes the pocket of interest. Therefore, the
      analysis presented here should prove helpful in guiding future structure-based
      ligand design efforts against Chk1.

PMID- 16289939
TI  - Synthesis and antimicrobial activity of N-alkyl and N-aryl piperazine
      derivatives.
AB  - A series of substituted piperazine derivatives have been synthesized and tested
      for antimicrobial activity. The antibacterial activity was tested against
      Staphylococcus aureus (MTCCB 737), Pseudomonas aeruginosa (MTCCB 741),
      Streptomyces epidermidis (MTCCB 1824) and Escherichia coli (MTCCB 1652), and
      antifungal activity against Aspergillus fumigatus, Aspergillus flavus and
      Aspergillus niger. All synthesized compounds showed significant activity against
      bacterial strains but were found to be less active against tested fungi. In vitro
      toxicity tests demonstrated that compounds 4d and 6a showed very less toxicity
      against human erythrocytes.

PMID- 16289940
TI  - Autonomic nervous evaluation in the early stages of olivopontocerebellar atrophy.
AB  - The clinical significance of evaluating autonomic nervous system functions in the
      early stages of olivopontocerebellar atrophy (OPCA) has been investigated in 13
      OPCA out-patients (7 males and 6 females, mean age: 51.0 years). We have employed
      measurements of blood pressure, plasma norepinephrine (NE), CVR-R, low-frequency
      power/high-frequency power ratio (L/H), high-frequency power (HF) score and heart
      rate (HR) monitoring using Holter ECG recording for evaluation of CVR-R. We have
      also carried out urodynamic examinations, focusing on the possible existence of
      bladder dysfunction. Although no significant changes were noted between control
      and OPCA groups concerning HR, CVR-R, L/H, plasma levels of norepinephrine and
      systolic blood pressure, HF (high-frequency power) (ms(2)), especially at night
      time, invariably showed a significant decline in OPCA groups. All OPCA patients
      who showed a decreased circadian HF also exhibited a tendency towards urinary
      bladder dysfunction. The present results appear to relate to disorder of the
      parasympathetic autonomic nervous system and neuromuscular dysfunction in the
      lower urinary tract. In conclusion, HRV (heart rate variability) analysis is a
      useful and safe tool and a keen predictor for evaluating functional states of
      autonomic nervous activity, especially in the early stages of OPCA. This study
      has also suggested the possible efficacy of urodynamic measurements in OPCA
      patients as an indicator of neuromuscular dysfunction in the lower urinary tract
      and of parasympathetic malfunction.

PMID- 16289941
TI  - Central autonomic integration of psychological stressors: focus on cardiovascular
      modulation.
AB  - During stress the sympathoadrenal system and the hypothalamo-pituitary-adrenal
      axis act in a coordinated manner to force changes within an animal's current
      physiological and behavioral state. Such changes have been described as 'fight
      flight' or stress responses. The central nervous system may generate a stress
      response by different neural circuits, this being dependent upon the type of
      stressor presented. For instance, the central control of the autonomic function
      during physical stress would seem to be based on existing homeostatic mechanisms.
      In contrast, with exposure to psychological stress the means by which autonomic
      outflow is regulated has not been fully established. This review discusses recent
      observations of autonomic flow, cardiovascular components in particular, during
      psychological stress and the possible implications these may have for our
      understanding of the central nervous system. In addition, an update of recent
      findings concerning several regions thought to be important to the regulation of
      autonomic function during psychological stress exposure is provided.

PMID- 16289942
TI  - Huntingtin is localized in the nucleus during preimplanatation embryo development
      in mice.
AB  - Huntington's disease (HD) is a dominant neurodegenerative disorder caused by the
      expansion of a CAG repeat in the gene encoding huntingtin. Moreover, the nuclear
      targeting of mutant huntingtin increases cellular toxicity, whereas normal
      huntingtin resides mainly in the cytoplasm, and is associated with membranes or
      microtubules. Huntingtin is enriched in neurons and its expression is increased
      during neural development. The inactivation of the HD gene results in embryonic
      lethality before nervous system development. Thus, huntingtin is critical during
      early embryonic development. Nevertheless, the function of huntingtin at this
      stage is unknown, even the distribution of the protein has not been described.
      The present study was undertaken to elucidate the distribution of huntingtin
      during the early developmental period in the mouse embryo. At the preimplantation
      stage, huntingtin was detected in nuclei up to 2.5 days post coitum (dpc), but
      disappeared from nuclei during the blastocyst stage (3.5 dpc). Following this
      stage, huntingtin was mainly localized in the cytoplasm and co-localized with
      mitotic spindles. These data suggest that the nuclear targeting of normal
      huntingtin is required during early embryo development in mice.

PMID- 16289943
TI  - Selected neurotrophins, neuropeptides, and cytokines: developmental trajectory
      and concentrations in neonatal blood of children with autism or Down syndrome.
AB  - Using a double-antibody immunoaffinity assay (Luminex) and ELISA technology, we
      measured concentrations of certain neurotrophins, neuropeptides, and cytokines in
      pooled samples (one to three subjects per sample) eluted from archived neonatal
      blood of children with later-diagnosed autism, Down syndrome, very preterm birth,
      or term control infants. We also measured analytes in blood from healthy adult
      controls. Case or control status for infant subjects was ascertained by
      retrospective review of service agency medical records. We observed inhibitory
      substances in eluates from archived bloodspots, especially marked for measurement
      of BDNF. Concentrations in control subjects differed by age: BDNF rose markedly
      with age, while NT-3 and NT-4/5 concentrations were lower in adults than in
      newborn infants. IL-8 concentrations were higher in newborn infants, preterm and
      term, than in adults. Considered by diagnostic group, total protein was higher in
      Down syndrome than in either autism or control subjects. In infants with Down
      syndrome, concentrations of IL-8 levels were higher than in controls, whether or
      not corrected for total protein; NT-3 and CGRP were lower and VIP higher. In
      samples from autistic subjects, NT-3 levels were significantly lower than
      controls and an increase in VIP approached statistical significance.
      Concentrations of NT-4/5 and CGRP were correlated in infants with autism but not
      in Down syndrome or controls. Some of these results differ from earlier findings
      using a single-antibody recycling immunoaffinity chromatography (RIC) system. We
      discuss interrelationships of VIP, NT-3 and IL-8 and their potential relevance to
      features of the neuropathology of autism or Down syndrome.

PMID- 16289945
TI  - Proteomic identification of glyceraldehyde 3-phosphate dehydrogenase as an
      inhibitory target of hydrogen peroxide in Arabidopsis.
AB  - Hydrogen peroxide (H2O2) is now recognised as a key signalling molecule in
      eukaryotes. In plants, H2O2 is involved in regulating stomatal closure,
      gravitropic responses, gene expression and programmed cell death. Although
      several kinases, such as oxidative signal-inducible 1 (OXI1) kinase and mitogen
      activated protein kinases are known to be activated by exogenous H2O2, little is
      known about the proteins that directly react with H2O2. Here, we utilised a
      proteomic approach, using iodoacetamide-based fluorescence tagging of proteins in
      conjunction with mass spectrometric analysis, to identify several proteins that
      might be potential targets of H2O2 in the cytosolic fraction of Arabidopsis
      thaliana, the most prominent of which was cytosolic glyceraldehyde 3-phosphate
      dehydrogenase (cGAPDH; EC 1.2.1.12). cGAPDH from Arabidopsis is inactivated by
      H2O2 in vitro, and this inhibition is reversible by the subsequent addition of
      reductants such as reduced glutathione (GSH). It has been suggested recently that
      Arabidopsis GAPDH has roles outside of its catalysis as part of glycolysis, while
      in other systems this includes that of mediating reactive oxygen species (ROS)
      signalling. Here, we suggest that cGAPDH in Arabidopsis might also have such a
      role in mediating ROS signalling in plants.

PMID- 16289944
TI  - Calretinin-immunoreactive unipolar brush cells in the developing human
      cerebellum.
AB  - We have studied the temporal and spatial characteristics of the development of
      unipolar brush cells (UBCs) in the human cerebellar vermis. Consistently with
      previous studies in rodents and cat, we have found that unipolar brush cells
      appear at a relatively late phase of cerebellar development and their development
      continues up to and beyond the first postnatal year. A series of 23 normal human
      brains, including 5 adult and 18 fetal or infant brains (between the 24th
      gestational week and the 11th postnatal month) were used. In order to visualize
      unipolar brush cells, calretinin-immunocytochemistry was performed on
      formaldehyde-fixed, paraffin-embedded blocks of the cerebellar vermis. Our
      results show that calretinin-immunoreactive unipolar brush cells are not yet
      present in the cerebellar vermis at the 28th gestational week. At birth, they are
      present in a relatively small number, mostly in the vestibular lobules. At the
      3rd, 5th, 8.5th and 11th postnatal months the number of calretinin-immunoreactive
      unipolar brush cells gradually increase, first appearing in the vestibular
      lobules, followed by the invasion of the later developing vermal lobules,
      spreading in a rostro-caudal and proximo-distal direction. Although at the 11th
      postnatal month unipolar brush cells exhibited adult-like morphological and
      distributional features, their number appeared to be lower than in the adult
      cerebellum. The late maturation of unipolar brush cells implies that the
      cytoarchitectonical development of the human cerebellum is not completed by the
      end of the first postnatal year.

PMID- 16289946
TI  - Functional markers and a 'systemic strategy': convergency between plant breeding,
      plant nutrition and molecular biology.
AB  - Research perspectives towards sustainable plant production through plant breeding
      on abiotic stress tolerance require interdisciplinary competence. The present
      paper wants to strengthen awareness of important activities or current insights
      in plant breeding, plant nutrition and molecular biology to facilitate
      approximation of the disciplines and to direct efforts in molecular biology early
      in development towards application. As a consequence of recent discussion on
      appropriate approaches in systems biology towards crop improvement, a global
      'systemic strategy' is presented to identify functional marker candidates for
      abiotic stress tolerance more efficiently.

PMID- 16289947
TI  - Buckwheat (Fagopyrum esculentum Moench) low molecular weight seed proteins are
      restricted to the embryo and are not detectable in the endosperm.
AB  - Buckwheat (Fagopyrum esculentum Moench) proteins are nutritionally important
      because of their high and balanced content of essential amino acids making their
      biological value much higher than that of cereal proteins. We analyzed extracts
      of buckwheat endosperm and embryo proteins by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). On electropherograms of endosperm
      proteins, six intense bands were detected. Two most intense bands were in the
      range of molecular weights (M.W.s) from 50 to 60 kDa. Protein of 57 kDa has been
      shown not to cross-react against antibodies raised against proteins of M.W.
      ranging between 23 and 25 kDa. There are no reports about the allergenicity of
      other endosperm proteins. On the electropherogram of buckwheat endosperm no low
      M.W. proteins could be detected. In this study we have demonstrated the tissue
      specific presence of proteins of different size classes of the endosperm and
      embryo tissues.

PMID- 16289949
TI  - HPLC analysis of plant DNA methylation: a study of critical methodological
      factors.
AB  - HPLC analysis of nucleosides is important for determining total DNA methylation
      in plants and can be used to help characterise epigenetic changes during stress,
      growth and development. This is of particular interest for in vitro plant
      cultures as they are highly susceptible to genetic change. HPLC methodologies
      have been optimised for mammalian and microbial DNA, but not for plants. This
      study examines critical methodological factors in the HPLC analysis of plant DNA
      methylation using in vitro cultures of Ribes ciliatum. HPLC revealed that
      complete removal of RNA from plant DNA extractions is difficult using RNase (A
      and T1) digestions and LiCl precipitation. This suggests that base analysis
      should be avoided when using these RNA removal techniques, as bases from residual
      RNA fragments will inflate peak areas for DNA-derived bases. Nucleoside or
      nucleotide analysis is therefore recommended as a more suitable option as RNA and
      DNA constituents can be readily separated. DNA digestion was also a critical
      factor as methylation was under-estimated following incomplete nuclease digestion
      and over-estimated following incomplete phosphatase digestion. The units of
      enzyme required for complete DNA digestion was optimised and found to be 20-200
      times less for nuclease P1 and 15 times less for alkaline phosphatase as compared
      with previous protocols. Digestion performance was conveniently monitored using
      marker peaks that indicate incomplete digestion products. This study identifies
      critical components of HPLC analysis and offers a comprehensive guide for the
      stringent analysis of DNA methylation in plants.

PMID- 16289948
TI  - Oxidation of the flavonoid eriodictyol by tyrosinase.
AB  - A pathway is proposed for the oxidation of the flavonoid eriodictyol by mushroom
      tyrosinase. In it, the enzymatic oxidation of eriodictyol leads to the formation
      of eriodictyol-o-quinone, which undergoes the nucleophilic attack of another
      eriodictyol unit to yield a dimer. This dimer is then oxidized by the eriodictyol
      o-quinone. The reaction was followed by recording the time course of formation of
      this second o-quinone at 475 nm. Progress curves at this wavelength showed the
      appearance of a lag, the length of which varied with enzyme and substrate
      concentrations, and which must have been caused by the chemical reactions taking
      place after the enzymatic reaction. When eriodictyol oxidation was studied in the
      presence of 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH), which
      competes with the substrate in the reaction with eriodictyol-o-quinone, the lag
      disappeared. The kinetic parameters were similar with and without MBTH.
      Eriodictyol oxidation was inhibited by tropolone, which behaved as a slow-binding
      inhibitor.

PMID- 16289950
TI  - N-acetyl glutamate kinase from Daucus carota suspension cultures: embryogenic
      expression profile, purification and characterization.
AB  - In Daucus carota, N-acetylglutamate-5-phosphotransferase (NAGK; E.C. 2.7.2.8)
      specific activity was shown to correlate with the progression of somatic
      embryogenesis and was highest in the latter stages, where growth was most rapid.
      The enzyme was subsequently purified greater than 1200-fold using heat treatment,
      ammonium sulfate fractionation, gel filtration, anion exchange and dye ligand
      chromatography. Carrot NAGK was shown to have a subunit molecular weight of 31
      kDa and form a hexamer. The Kms for NAG and ATP are 5.24 and 2.11 mM,
      respectively. Arginine (Arg) is a K-type allosteric inhibitor of the enzyme, and
      Hill coefficients in the order of 5 in the presence of Arg suggest that the
      enzyme is highly cooperative. D. carota NAGK does not bind to Arabidopsis
      thaliana PII affinity columns, nor does the A. thaliana PII increase NAGK
      specific activity, indicating its cellular location is probably different.

PMID- 16289951
TI  - Molecular analysis of Salmonella enterica subsp. enterica serovar Agona isolated
      from slaughter pigs.
AB  - Salmonella enterica subsp. enterica (S.) serovar Agona plays an important role in
      Brazil as causative agent of salmonellosis in food-producing animals - in
      particular, pigs and poultry - as well as in humans. A total of 45 S. Agona
      isolates collected from slaughter pigs at three different slaughterhouses in
      Southern Brazil was investigated in this study for their phenotypic and genotypic
      relatedness. For this, the antimicrobial susceptibility patterns and the phage
      types were determined. Molecular analysis included the determination of plasmid
      profiles as well as the analysis of XbaI- and BlnI-generated macro-restriction
      patterns. Moreover, a novel typing method called subtracted restriction
      fingerprinting (SRF) was successfully applied to the S. Agona isolates. Based on
      all properties determined, a dominant clonal group comprising 33 of the 45
      isolates was identified. Members of this group were susceptible to all
      antimicrobials tested, did not carry plasmids, shared the same phage type and
      were closely related or even indistinguishable by their EcoRI-PauI SRF patterns
      as well as their XbaI and BlnI macro-restriction patterns. Members of this clonal
      group were identified at all 3 slaughterhouses at variable frequencies and
      originated from pig herds raised in 15 different cities in Southern Brazil which
      were located up to 450 km apart from each other. Since the S. Agona-carrying
      slaughter pigs were from various integrated production lines, the results of this
      study suggest that a specific clonal group of S. Agona had entered numerous pig
      production lines. This observation supports the requirement for the establishment
      of monitoring and control programmes in Brazil which should also include
      molecular techniques to better trace the dissemination of S. Agona and other
      Salmonella serovars in pigs and other food-producing animals.

PMID- 16289952
TI  - Genetic diversity in fluoroquinolone and macrolide-resistant Campylobacter coli
      from pigs.
AB  - The genetic diversity of 115 Campylobacter coli strains, isolated from pigs of 59
      geographical distant farms in Switzerland, were characterized on the basis of
      their DNA fingerprints and resistance to macrolides and fluoroquinolones.
      Sequence analysis showed that the macrolide-resistant isolates had a point
      mutation in the 23S ribosomal RNA (rRNA) genes (A2075G) and that the
      fluoroquinolone-resistant isolates had a point mutation in the gyrase gene gyrA
      (C257T). One fluoroquinolone-resistant strain had an additional transition
      mutation in the gyrB gene (A1471C). The flaA restriction fragment length
      polymorphism (RFLP) genotyping revealed that 57% of the isolates were genetically
      different. Point mutations in the 23S rRNA and gyrA genes could be found in both
      genetically distant and genetically related isolates. Additionally, isolates with
      and without point mutations were found within individual farms and on different
      farms. This study showed that the ciprofloxacin and erythromycin-resistant C.
      coli population present on the pig farms is not issued from a common ancestral
      clone, but individual Campylobacter strains have most likely mutated
      independently to acquire resistances under the selective pressure of an
      antibiotic.

PMID- 16289954
TI  - Efficient PCR-based gene targeting with a recyclable marker for Aspergillus
      nidulans.
AB  - The rapid accumulation of genomic sequences from a large number of eukaryotes,
      including numerous filamentous fungi, has created a tremendous scientific
      potential, which can only be realized if precise site-directed genome
      modifications, like gene deletions, promoter replacements, in-frame GFP fusions
      and specific point mutations can be made rapidly and reliably. The development of
      gene-targeting techniques in filamentous fungi and other higher eukaryotes has
      been hampered because foreign DNA is predominantly integrated randomly into the
      genome. For Aspergillus nidulans, we have developed a flexible method for gene
      targeting employing a bipartite gene-targeting substrate. This substrate is made
      solely by PCR, which obviates the need for bacterial subcloning steps. The method
      reduces the number of false positives and can be used to produce virtually any
      genome alteration. A major advance of the method is that it allows multiple
      subsequent genome manipulations to be performed as the selectable marker is
      recycled.

PMID- 16289955
TI  - Comparative analysis of Cryptococcus neoformans acid-resistant particles
      generated from pigmented cells grown in different laccase substrates.
AB  - Cryptococcus neoformans produces pigments in vitro in the presence of exogenous
      substrate. We characterized acid-resistant particles isolated from pigmented
      cells grown in L-dopa, methyl-dopa, (-)-epinephrine or (-)-norepinephrine. The
      goals of this study were to determine whether pigments made from each of these
      substrates were melanins and the consequences of pigmentation on related cell
      characteristics. The greatest yield of acid-resistant particles occurred with
      methyl-dopa followed by L-dopa. Electron microscopy indicated that L-dopa and
      methyl-dopa produced particles with thicker shells. The mAb 6D2 reacted with all
      particles, but a lower reactivity was observed with epinephrine-derived
      particles. ESR analysis revealed that epinephrine-derived particles failed to
      produce a stable free radical signal typical of melanins. Growth of C. neoformans
      in different substrates affected cell and capsule size but not capsule induction.
      Hence, the type of pigment produced by C. neoformans is dependent on the
      substrate and not all pigments meet the criteria for melanins.

PMID- 16289956
TI  - Detection, quantification and confirmation of anabolic steroids in equine plasma
      by liquid chromatography and tandem mass spectrometry.
AB  - Anabolic androgenic steroids are related to the male sex hormones and are abused
      in equine sports. In an effort to deter the abuse of anabolic steroids, a
      sensitive LC-MS/MS method was developed for detection, quantification and
      confirmation of eight major anabolic steroids (testosterone, normethandrolone,
      nandrolone, boldenone, methandrostenolone, tetrahydrogestrinone (THG),
      trenbolone, and stanozolol) in equine plasma. Formation of solvent adduct ions of
      the analytes was observed under electrospray ionization (ESI) conditions, and
      desolvation of the solvent adduct ions by source collision-induced decomposition
      (CID) increased the abundance of the [M+H]+ ions as well as the multiple-reaction
      monitoring (MRM) signals. ESI (+) and APCI (+) were compared with respect to
      sensitivity for the analytes and the former provided better sensitivity. The
      matrix effect on ion suppression or enhancement was evaluated, and was
      negligible. Confirmation of the analytes was performed using criteria of three
      ion transitions and LC retention time of each analyte. The limit of detection
      (LOD) and quantification (LOQ) was 25 pg/mL. The limit of confirmation (LOC) was
      25 pg/mL for boldenone; 50 pg/mL for normethandrolone, nandrolone, and
      methandrostenolone; and 100 pg/mL for testosterone, THG, trenbolone, and
      stanozolol. The analytes were evaluated for stability and found to be stable in
      plasma for 24h at room temperature, 13 days at 4 degrees C, and 34 days at -20
      and -70 degrees C. The method was successfully applied to analyses of equine
      plasma samples for pharmacokinetics study. This method is sensitive and useful
      for detection, quantification and confirmation of these anabolic steroids in
      equine plasma.

PMID- 16289957
TI  - Quasi-isoelectric buffers for protein analysis in a fast alternative to
      conventional capillary zone electrophoresis.
AB  - Two different approaches are here reported for obtaining ultra-narrow pI cuts
      from 2-pH unit wide carrier ampholyte ranges, as commercially available, for use
      as quasi-isoelectric buffers in capillary electrophoresis separations of
      proteins. One of them uses multicompartment electrolyzers endowed with
      isoelectric membranes (Immobiline technology); the other employs the Rotofor
      equipment. Although the first approach results in more precise pI cuts, the
      latter technique is much faster, easier to handle and permits the immediate
      collection of 20 fractions in a single run. This results in ultra-narrow, ca. 0.1
      pH unit intervals, uniformly spaced apart along the original wider gradient
      utilized for the fractionation. It is here shown that such quasi-isoelectric
      buffers, especially those in the pH 8-9 interval, have the unique property of
      coating the silica wall, thus preventing interaction of the proteins with the
      silica surface, that would otherwise totally disrupt the separation. On the
      contrary, such a shielding is not obtained in control, non isoelectric buffers
      (such as phosphate), that give very poor separations in uncoated capillaries. It
      is hypothesized that such a unique shielding effect is due to the oligo-amino
      backbone of the carrier ampholytes, typically composed (in the Vesterberg's
      synthetic approach) of 4-6 nitrogens spaced apart by ethylene moieties. Although
      such oligoprotic buffers should bear, in the isoelectric state, just one positive
      and one negative charge, they might be transiently ionized upon contact with the
      silanols, thus inducing a cooperative binding to the silica wall.

PMID- 16289953
TI  - Microarray analysis of expressed sequence tags from haustoria of the rust fungus
      Uromyces fabae.
AB  - Rust fungi are plant parasites which colonise host tissue with an intercellular
      mycelium that forms haustoria within living plant cells. To identify genes
      expressed during biotrophic growth, EST sequencing was performed with a
      haustorium-specific cDNA library from Uromyces fabae. One thousand seventeen ESTs
      were generated, which assembled into 530 contigs. Several of the most frequently
      represented sequences in the EST database were identical to the in planta induced
      genes (PIGs) identified previously (Hahn, M., Mendgen, K., 1997. Characterisation
      of in planta-induced rust genes isolated from a haustorium-specific cDNA library,
      Mol. Plant-Microbe Interact. 10, 427-437). Virus-encoded sequences were
      identified, providing evidence for two novel RNA mycoviruses in U. fabae.
      Microarray hybridisation revealed many cDNAs that were significantly activated in
      rust-infected leaves compared to germinated uredospores. Very strong in planta
      expression was found for two PIGs encoding putative metallothioneins.
      Furthermore, several genes involved in ribosome biogenesis and translation,
      glycolysis, amino acid metabolism, stress response, and detoxification showed an
      increased expression in the parasitic mycelium. These data indicate a strong
      shift in gene expression in rust fungi between germination and the biotrophic
      stage of development.

PMID- 16289958
TI  - Thymic expression of mutated B16:A preproinsulin messenger RNA does not reverse
      acceleration of NOD diabetes associated with insulin 2 (thymic expressed insulin)
      knockout.
AB  - We detected insulin2 mRNA but not insulin1 in thymus using real-time PCR
      analysis. Transgenic expression of a mutated insulin message (alanine rather than
      tyrosine at insulin B chain amino acid 16) was variably induced in thymus of four
      transgenic founder strains. The transgenic message levels were as high or higher
      than native insulin2 message. Lack of the insulin2 gene resulted in the
      enhancement of anti-insulin autoantibodies (regular NOD vs insulin2-knockout NOD,
      P<0.001) and in the presence of the B16:A insulin transgenes, levels of insulin
      autoantibodies remained elevated (regular NOD vs insulin2-knockout NOD with B16:A
      insulin, P<0.01). Diabetes acceleration by the knockout of the insulin2 gene was
      not influenced by the presence of the B16:A insulin transgenes. These data
      suggest that the B16:A insulin does not compensate for lack of native insulin
      expression in thymus. If lack of thymic insulin message of the insulin2 knockout
      is the cause of diabetes acceleration, this suggests that native insulin B:9-23
      sequences may be crucial in thymus for insulin mediated immunomodulation. Further
      experiments varying native insulin message expression in thymus is necessary for
      direct comparison, but the current study provides additional evidence of the
      potential important role of a specific insulin B chain epitope.

PMID- 16289959
TI  - N-Methylcarbamoyl-lysine adduct in globin: a new metabolic product and potential
      biomarker of N, N-dimethylformamide in humans.
AB  - Metabolism of the solvents N,N-dimethylformamide (DMF) and N-methylformamide (MF)
      results in the formation of N-methylcarbamoyl adducts at the N-terminal valine
      and lysine in blood protein globin, of which the lysine adduct has so far only
      been reported in rats given high doses of both solvents [Mraz, J., Simek, P.,
      Chvalova, D., Nohova, H., Smigolova, P., 2004. Studies on the methyl isocyanate
      adducts in globin. Chem. Biol. Interact. 148, 1-10]. Here we examined whether the
      lysine adduct is produced, and accessible to analysis, in humans occupationally
      or experimentally exposed to DMF. Globin from exposed subjects (n=35) and
      unexposed controls (n=5) was analyzed by two methods. Edman degradation was used
      as a sensitive reference method to measure the valine adduct by converting it to
      3-methyl-5-isopropylhydantoin (MVH). The MVH levels in globin of the exposed
      subjects were in the range of 1-441 nmol/g, in controls <1 nmol/g. The principal
      method of globin analysis consisted of enzymatic hydrolysis with pronase to
      release free N(epsilon)-(N-methylcarbamoyl)lysine (MLU) and N
      methylcarbamoylvaline (MVU), which were determined by HPLC/MS/MS, with no clean
      up or preconcentration steps needed. For MLU, the parent and product ions were
      m/z 204-->173, and the limit of detection was approximately 5 nmol/g globin. MLU
      was found in most globins from the exposed subjects but not in the controls. A
      close correlation between the MLU and MVH levels (nmol/g) was observed:
      MLU=7+0.48 MVH (R(2)=0.84, n=32). In conclusion, MLU can be easily measured in
      globin of workers exposed to DMF. The findings also indicate a long-term
      persistence of MLU in the human body, and consequently, its potential as a
      biomarker of chronic exposure to DMF.

PMID- 16289961
TI  - Induction of cytokines by heat shock proteins and concanavalin A in murine
      splenocytes.
AB  - There has been considerable interest in the effect of heat shock proteins (HSPs)
      on the innate immune system. Whether HSPs have any direct effects on the
      activation of lymphocytes is not clear. Using gene expression array, protein
      array and enzyme-linked immunosorbent assay, we demonstrated that highly purified
      recombinant murine Hsp60 (rmHsp60), essentially free of lipopolysaccharide
      contamination, had no effect in the expression of 113 cytokine genes and the
      release of 22 common cytokines including interferon-gamma (IFN-gamma) and
      interleukin-2 (IL-2) by murine splenocytes. Likewise, recombinant human Hsp60
      (rhHsp60) and rhHsp70 had no effect in the release of IFN-gamma and IL-2. In
      contrast, concanavalin A induced the expression of a number of cytokine genes and
      the release of IFN-gamma and IL-2. These results suggest that Hsp60 and Hsp70 do
      not induce cytokine production by murine splenocytes.

PMID- 16289960
TI  - Upregulation of neuropilin-1 by basic fibroblast growth factor enhances vascular
      smooth muscle cell migration in response to VEGF.
AB  - Neuropilin-1 (NRP-1) is a co-receptor for vascular endothelial growth factor
      (VEGF). During neovascularization, vascular smooth muscle cells (VSMCs) and
      pericytes modulate the function of endothelial cells. Factors that mediate NRP-1
      in human VSMCs (hVSMCs) remain to be elucidated. We studied various angiogenic
      cytokines to identify factors that increase NRP-1 expression in hVSMCs. Treatment
      of hVSMCs with basic fibroblast growth factor (b-FGF) induced expressions of NRP
      1 mRNA and protein whereas epidermal growth factor, insulin-like growth factor-1,
      and interleukin-1beta did not. b-FGF induced phosphorylation of Erk-1/2 and JNK.
      MEK1/2 and nuclear factor kappa B (NF-kappaB) inhibitors (U0126 and TLCK,
      respectively) blocked the ability of b-FGF to induce NRP-1 mRNA expression, but
      inhibition of JNK (SP600125) or PI3-kinase activity (wortmannin) did not.
      Further, the increase in NRP-1 expression by b-FGF enhanced hVSMCs migration in
      response to VEGF(165). This effect was dependent on the binding of VEGF(165) to
      VEGFR-2, as blocking antibodies to VEGFR-2, but not VEGFR-1, inhibited VEGF(165)
      induced migration. In conclusion, b-FGF increased NRP-1 expression in hVSMCs that
      in turn enhance the effect of VEGF(165) on cell migration. The enhanced migration
      of hVSMCs was mediated through binding of VEGF(165) to both NRP-1 and VEGFR-2, as
      inhibition of VEGFR-2 on these cells blocked the effect of VEGF-mediated cell
      migration.

PMID- 16289962
TI  - Characterization of dynamic processes using deuterium in uniformly 2H,13C,15N
      enriched peptides by MAS solid-state NMR.
AB  - We present in this paper 2H,13C MAS correlation experiments that are performed on
      a uniformly 2H,13C,15N labeled sample of Nac-Val, and on the uniformly 2H,15N
      labeled dipeptide Nac-Val-Leu-OH. The experiments involve the measurement of 2H
      T1 relaxation times at two different magnetic fields, as well as the measurement
      of the 2H tensor parameters by evolution of the 2H chemical shift. The data are
      interpreted quantitatively to differentiate between different side chain motional
      models.

PMID- 16289963
TI  - Sectoral sampling in centric-scan SPRITE magnetic resonance imaging.
AB  - A new approach to the construction of k-space trajectories for centric-scan
      SPRITE in both 2D and 3D is presented. All benefits of previous SPRITE methods
      are retained, most importantly the ability to image objects with short T*(2).
      This new approach gives more flexibility in the choice of number of interleaves
      with points more evenly distributed across k-space. All these improvements
      positively contribute to image quality and resolution, which can be also traded
      off against experimental speed. Sectoral sampling will have significant benefits
      for magnetisation preparation contrast imaging.

PMID- 16289964
TI  - Multibore sample cell increases EPR sensitivity for aqueous samples.
AB  - We have performed calculations, verified by experiment, to explain why the
      sensitivity of biological EPR can be dramatically increased by dividing the
      aqueous sample into separate compartments. In biological EPR, the major factor
      affecting sensitivity is the number of spins in the sample. For an aqueous sample
      at ambient temperature, this is limited by the requirement for a small volume,
      due to strong non-resonant absorption of microwaves by water. However, recent
      empirical studies have shown that this volume limitation can be greatly relieved
      by dividing the aqueous sample into separate volumes, which allows much more
      aqueous sample to be loaded into a resonant cavity without significant
      degradation of the cavity quality factor. Calculations, based on the Bruggeman
      mixing rule, show quantitatively that the composite aqueous sample has a
      permittivity much less than that of bulk water, depending on the aqueous volume
      fraction f. Analysis for X-band EPR spectroscopy shows that the optimal volume
      fraction of an aqueous composite sample, producing maximum sensitivity, is
      f=0.15, increasing the sensitivity by a factor of 8.7, compared with an aqueous
      sample in a single tube.

PMID- 16289965
TI  - The role of SMG-1 in nonsense-mediated mRNA decay.
AB  - SMG-1, a member of the PIKK (phosphoinositide 3-kinase related kinases) family,
      plays a critical role in the mRNA quality control system termed nonsense-mediated
      mRNA decay (NMD). NMD protects the cells from the accumulation of aberrant mRNAs
      with premature termination codons (PTCs) that encode nonfunctional or potentially
      harmful truncated proteins. SMG-1 directly phosphorylates Upf1, another key
      component of NMD, and this phosphorylation occurs upon recognition of PTC on post
      spliced mRNA during the initial round of translation. At present, a variety of
      tools are available that can specifically suppress NMD, and it is possible to
      examine the contribution of NMD in a variety of physiological and pathological
      conditions.

PMID- 16289966
TI  - Activation of Epstein-Barr virus/C3d receptor (gp140, CR2, CD21) on human B
      lymphoma cell surface triggers Cbl tyrosine phosphorylation, its association with
      p85 subunit, Crk-L and Syk and its dissociation with Vav.
AB  - It is well established that CD21 activation on human B cell surface triggers B
      cell proliferation. We previously demonstrated that CD21 activation also triggers
      tyrosine phosphorylation of two components, p95 and p120, both interacting with
      SH2 domains of the p85 subunit of PI 3-kinase. We successively identified p95 as
      the nucleolin and the first signal transduction pathway specifically triggered by
      CD21 activation, i.e.: pp60Src activation, tyrosine phosphorylation of p95
      nucleolin, its interaction with SH2 domains of p85 subunit and PI 3-kinase
      activation, followed by AKT-GSK-3 activations. We herein identified the p120
      component as the protooncoprotein Cbl and the first steps associated to its
      activation. First, CD21 activation triggered Cbl tyrosine phosphorylation, which
      required c-Src kinase but not PI 3-kinase or Syk kinase activities. Involvement
      of Src kinase in this step was supported by inhibition of Cbl phosphorylation and
      its interactions with other components when cells were either preincubated with
      specific Src inhibitor or transfected with dominant-negative c-Src form. Second,
      once tyrosine phosphorylated, Cbl interacts with SH2 domains of p85 subunit, SH2
      domains of Crk-L and with tyrosine phosphorylated Syk kinase. The third and
      unexpected feature was to found that, at the contrary of BCR or of CD19 (herein
      also analyzed for the first time), CD21 activation triggers dissociation of Cbl
      Vav complex. Thus, these results provide the first molecular basis of a new
      signal transduction pathway specifically triggered by CD21 activation.

PMID- 16289967
TI  - Measuring Ras-family GTP levels in vivo--running hot and cold.
AB  - The detection of Ras-family GTPase activity is important in the determination of
      cell signaling events elicited by numerous ligands and cellular processes. This
      has been made much easier in recent years by the use of glutathione S-transferase
      (GST)-fused Ras binding domains. These domains from downstream effectors such as
      Raf and RalGDS preferentially bind the GTP-bound Ras proteins enabling their
      extraction and subsequent quantification by immunoblotting. Despite this advance,
      effectors that efficiently discriminate between GTP- and GDP-bound states are not
      available for many Ras-family members. While this hampers the ability to detect
      activity in tissue specimens, it is still possible to metabolically label cells
      with (32)Pi to load the GTP/GDP pool with labeled nucleotides, immunoprecipitate
      the Ras protein and detect the bound label following thin layer chromatographic
      separation and exposure to film or a phosphorimager. Using a transfection system
      and antibodies that recognize epitope tags one can test the ability of a protein
      to work as a GEF or GAP for a certain GTPase. Alternatively, if an
      immunoprecipitating antibody is available to the target GTPase, then analysis of
      endogenous GTP/GDP ratio is possible. Here we describe the detection of M-Ras and
      Rap1 activity by GST-RBD pull-down as well as that of Rheb and epitope-tagged R
      Ras by classical metabolic labeling and immunoprecipitation.

PMID- 16289968
TI  - Fluorescence approaches for monitoring interactions of Rho GTPases with
      nucleotides, regulators, and effectors.
AB  - To understand the manner in which biological macromolecules interact with each
      other, we need not only structural information, but also details of kinetics and
      thermodynamics of the processes involved. This is particularly important for key
      proteins acting in signal transduction such as the small GTPases of the Ras
      superfamily. The complexity of their roles is constantly increasing since a large
      number of GTPases have been identified and each of these in turn interacts with a
      variety of regulatory and signaling proteins such as GAPs, GEFs, and downstream
      effectors. There are a number of methods that can be used to characterize the
      specificity, strength, and stoichiometry of such intermolecular interactions, to
      understand the effect of binding on the protein structure, and, ultimately, to
      obtain insights into their biological functions. This article discusses the use
      of fluorescence spectroscopic methods, which allows real-time monitoring of
      ligand- and protein-protein interactions at submicromolar concentrations, and
      quantification of the kinetic and equilibrium constants. Fluorescently labeled
      guanine nucleotides serve as fluorescence reporter groups to investigate the
      interactions of GTPases of the Rho family (e.g., RhoA, Rac1, and Cdc42). We
      present examples for quantitative characterization of (i) Rac1 x GDP interaction,
      (ii) Cdc42-interaction with the GTPase binding domain of the Wiskott Aldrich
      syndrome protein (three alternative approaches), (iii) accelerated nucleotide
      exchange reaction of RhoA by the catalytic domains of p190RhoGEF, and (iv)
      intrinsic and stimulated GTP-hydrolysis reaction by the catalytic domain of
      p50RhoGAP.

PMID- 16289969
TI  - Analysis of Ras and Rap activation in living cells using fluorescent Ras binding
      domains.
AB  - Ras GTPases regulate cellular growth and differentiation and are modulated by
      myriad stimuli including growth factors, cytokines, antigens, and UV irradiation.
      Ras GTPases are molecular switches that are active when GTP-bound and inactive
      when GDP-bound. The ability of these GTPases to signal requires that the GTP
      bound form engage downstream effectors, interactions that occur only on the
      cytosolic surface of cellular membranes. Ras family proteins include H-Ras, N
      Ras, K-Ras, and Rap1. Insight into the regulation and signaling properties of
      these molecules has come largely from in vitro studies relying on cellular
      extracts prepared following cellular stimulation. Since Ras GTPases are expressed
      on multiple cellular compartments that include the plasma membrane, vesicles
      derived from the plasma membrane, and other internal membranes such as the ER and
      Golgi complex, analysis of how their spatial distribution modulates signaling has
      remained unknown. We have developed fluorescent, GFP-based probes capable of
      selectively binding GTP-bound Ras or Rap1 in living cells. We have used these
      reporters to examine sites of cellular activation of Ras and Rap1 during growth
      factor stimulation. These studies have revealed new insights into the platforms
      from which these GTPases signal and have led to the hypothesis that GTPase
      signaling is modulated in a compartmentalized fashion. Here, we describe the
      design and implementation of fluorescent probes for Ras and Rap1.

PMID- 16289970
TI  - Analysis of monomeric GTPases of the Ras and Rho families.

PMID- 16289971
TI  - Oestrous cycle of captive southern hairy-nosed wombats (Lasiorhinus latifrons) in
      South Australia, Australia.
AB  - There is limited information available on the oestrous cycle of female southern
      hairy-nosed wombats (Lasiorhinus latifrons). This is mainly due to an extremely
      poor breeding success in captivity and the difficulty in routine recapturing of
      these cryptic, semi-fossorial animals in the wild. The aim of this study was to
      characterise the oestrous cycle of this species by monitoring peripheral plasma
      concentrations of progesterone and oestradiol, assessing changes in vaginal
      cytology, pouch condition and the urogenital sinus. Eight adult female wombats
      were monitored during the breeding season (July-December) over 2 years (2002
      2003). Samples were collected up to three times a week. Vaginal smears contained
      several cell types, categorised by morphology, as either superficial epithelial
      cells or parabasal-intermediate cells. Leucocytes were also counted. Plasma
      progesterone profiles showed a mean oestrous cycle length of 36.33+/-0.67 days
      with a peak progesterone concentration of 139.53+/-10.62nmol/L. Levels of
      oestradiol peaked at a mean level of 467.33+/-44.32pmol/L on average 5 days
      before a rise in plasma progesterone values. The proportion of epithelial cells
      in vaginal smears varied throughout the cycle, with a high percentage of
      superficial epithelial cells observed during the follicular phase. During periods
      when progesterone concentrations were high, a greater percentage of parabasal
      intermediate cells was observed. In conclusion, this study has characterised the
      oestrous cycle of the southern hairy-nosed wombat and confirmed that changes in
      vaginal smears together with pouch and urogenital sinus details could be used to
      determine signs of oestrus in this species.

PMID- 16289972
TI  - Effect of culture conditions on the obtention of boar epididymal epithelial cell
      monolayers.
AB  - The goal of this study was to investigate the effect of the collagenase digestion
      time, the initial density of fragments and the culture temperature on the
      obtention of a boar epididymal epithelial cell culture, which is a useful
      methodology for the study of epididymal functions. A confluent monolayer of
      caput, corpus and cauda epididymal epithelial cells was only obtained when an
      adequate enzymatic digestion of the connective tissue surrounding the epididymal
      tubule was performed. For the correct digestion of caput and corpus fragments two
      collagenase digestions of 2 and 1h, respectively, were enough. Cauda fragments,
      however, needed two collagenase digestions of 3h each. A confluent monolayer of
      caput, corpus and cauda epididymal epithelial cells was obtained regardless of
      the initial density tested (15, 30, 60 and 90fragments/well). However, cultures
      originated from 15 and 30fragments/well showed higher cell concentration during
      the first 2 weeks of culture than cultures originated from 60 and
      90fragments/well. A confluent monolayer of caput, corpus and cauda epididymal
      epithelial cells was obtained at both 32 and 37 degrees Celsius, but at 32
      degrees Celsius cells grew very slowly and confluence was not reached until a
      week later than it was with cells growing at 37 degrees Celsius. In conclusion,
      we have observed that the time of digestion with collagenase is an important
      factor for the successful establishment of boar epididymal cell monolayers, and
      that the initial density of fragments and the culture temperature should be taken
      into account.

PMID- 16289973
TI  - A connection rule for alpha-carbon coarse-grained elastic network models using
      chemical bond information.
AB  - A sparser but more efficient connection rule (called a bond-cutoff method) for a
      simplified alpha-carbon coarse-grained elastic network model is presented. One of
      conventional connection rules for elastic network models is the distance-cutoff
      method, where virtual springs connect an alpha-carbon with all neighbor alpha
      carbons within predefined distance-cutoff value. However, though the maximum
      interaction distance between alpha-carbons is reported as 7 angstroms, this
      cutoff value can make the elastic network unstable in many cases of protein
      structures. Thus, a larger cutoff value (>11 angstroms) is often used to
      establish a stable elastic network model in previous researches. To overcome this
      problem, a connection rule for backbone model is proposed, which satisfies the
      minimum condition to stabilize an elastic network. Based on the backbone
      connections, each type of chemical interactions is considered and added to the
      elastic network model: disulfide bonds, hydrogen bonds, and salt-bridges. In
      addition, the van der Waals forces between alpha-carbons are modeled by using the
      distance-cutoff method. With the proposed connection rule, one can make an
      elastic network model with less than 7 angstroms distance cutoff, which can
      reveal protein flexibility more sharply. Moreover, the normal modes from the new
      elastic network model can reflect conformational changes of a given protein
      better than ones by the distance-cutoff method. This method can save the
      computational cost when calculating normal modes of a given protein structure,
      because it can reduce the total number of connections. As a validation, six
      example proteins are tested. Computational times and the overlap values between
      the conformational change and infinitesimal motion calculated by normal mode
      analysis are presented. Those animations are also available at UMass Morph Server
      (http://biomechanics.ecs.umass.edu/umms.html).

PMID- 16289974
TI  - Seasonal variations in onset of symptoms in Crohn's disease.
AB  - BACKGROUND: Seasonal variations in onset of symptoms have been reported in
      ulcerative colitis but not in Crohn's disease. AIM.: To investigate whether our
      inflammatory bowel diseases patients presented seasonal variations in onset of
      symptoms. PATIENTS AND METHODS: Patients with a diagnosis of inflammatory bowel
      diseases established between 1995 and May 2004, and consecutively observed from
      June 2003 to May 2004, were included in the study. Onset of symptoms (year,
      season and month) was recorded. Expected onsets with a uniform distribution
      during the year were calculated and compared to observed onsets. STATISTICAL
      ANALYSIS: chi-square test, odds ratio (95% confidence interval). RESULTS: Overall
      425 inflammatory bowel diseases patients were enrolled. Onset of symptoms (year
      and season) was established in 353/425 patients (83%; 150 Crohn's disease; 203
      ulcerative colitis). Onset of symptoms in inflammatory bowel diseases patients as
      a whole occurred more frequently in spring-summer compared to autumn-winter (odds
      ratio 1.39; 95% confidence interval 1.03-1.87; p<0.03). This variation was
      observed in Crohn's disease (odds ratio 1.59; 95% confidence interval 1.00-2.51;
      p<0.05) and a similar trend, although not significant, was observed in ulcerative
      colitis (odds ratio 1.27; 95% confidence interval 0.86-1.88; p=0.27).
      CONCLUSIONS: These data indicate that onset of Crohn's disease symptoms occurred
      more frequently during spring-summer. A similar trend was observed in ulcerative
      colitis. Environmental factors, such as associated infections, smoking, use of
      drugs and seasonal changes in immune function may be responsible for triggering
      the clinical onset of inflammatory bowel diseases.

PMID- 16289975
TI  - Targeted therapy in colorectal cancer: do we know enough?
AB  - The present paper is a critical review about the recent development of new agents
      that have revolutioned the therapeutical approach of solid tumours with a
      particular focus on colorectal cancer. Until a few years ago, chemotherapy has
      been considered the only medical treatment for advanced disease. At the moment,
      new drugs blocking some cell functions, such as monoclonal antibodies or tyrosin
      kinase inhibitors are available for many oncologists, but their efficacy should
      be debated for several reasons. Despite having a strong biological and
      preclinical rationale, the clinical results of these agents are not comparable to
      the results obtained by imatinib in gastrointestinal stromal tumour or in chronic
      myeloid leukaemia even though superior to chemotherapy alone. Moreover, the
      efficacy does not show any correlation with the molecular expressions of the
      tumours. In this review, we considered different hypotheses in order to explain
      these results.

PMID- 16289976
TI  - Intra-oesophageal acid suppression in complicated gastro-oesophageal reflux
      disease: esomeprazole versus lansoprazole.
AB  - BACKGROUND: Acid suppression is the mainstay of therapy in gastro-oesophageal
      reflux disease. Esomeprazole 40 mg is more effective than lansoprazole 30 mg in
      healing mucosal lesions in severe erosive reflux oesophagitis. However, data
      comparing esomeprazole with lansoprazole in patients with complications of gastro
      oesophageal reflux disease, such as ulcerative reflux oesophagitis and Barrett's
      oesophagus, are lacking. AIM: To compare the efficacy of esomeprazole and
      lansoprazole at their standard dosages in suppressing oesophageal acid exposure
      in complicated gastro-oesophageal reflux disease. METHODS: Thirty patients with
      complicated gastro-oesophageal reflux disease (7 with ulcerative reflux
      oesophagitis and 23 with Barrett's oesophagus), randomly assigned to receive 40
      mg esomeprazole (n=16) or 30 mg lansoprazole (n=14) once daily, underwent
      oesophageal 24-h pH monitoring while on therapy. Total, upright diurnal and
      supine nocturnal percentage acid reflux time were assessed. RESULTS: Esomeprazole
      was significantly more effective than lansoprazole in decreasing oesophageal acid
      exposure. Normalisation of both total and supine nocturnal percentage acid reflux
      time was obtained in 12 of 16 (75%) patients treated with esomeprazole but only
      in 4 of 14 (28%) cases treated with lansoprazole (p=0.026). CONCLUSIONS:
      Normalisation of oesophageal acid exposure can be achieved in the majority of
      complicated gastro-oesophageal reflux disease cases with esomeprazole 40 mg once
      daily.

PMID- 16289977
TI  - Diacylglycerol oil ingestion in type 2 diabetic patients with
      hypertriglyceridemia.
AB  - OBJECTIVE: Coronary arteriosclerotic heart disease frequently develops in
      patients with diabetes. Decreases in [corrected] serum high-density lipoprotein
      cholesterol (HDL-C) [corrected] concentration and low-density lipoprotein (LDL)
      particle size, accompanied by hypertriglyceridemia, are associated with the onset
      of atherosclerosis. We recently reported that hypertriglyceridemia was
      significantly improved in patients with type 2 diabetes who ingested
      diacylglycerol (DAG) oil. The effect on variables, including LDL particle size
      related to lipid metabolism, however, was not examined. The present study
      investigated the effects on these variables in more detail. METHODS: Patients
      with type 2 diabetes (n = 24) were assigned to receive DAG oil or triacylglycerol
      oil, and a 3-mo, single-blind, controlled study was performed. Patients replaced
      cooking oil in their daily diet with DAG or triacylglycerol oil, and
      anthropometry and blood sampling were performed at monthly intervals. RESULTS:
      There were no significant differences in calorie intake or amount of test oil
      ingested between groups. Waist circumference and serum triacylglycerol
      concentrations were significantly lower and serum concentrations of high-density
      lipoprotein cholesterol and apolipoprotein-AI were significantly higher in the
      DAG oil group than in the triacylglycerol oil group. Plasma plasminogen activator
      inhibitor-1 concentrations were significantly lower in the DAG oil group. LDL
      particle size tended to increase in the DAG oil group and was significantly
      larger in patients who had a small initial LDL particle size (<25.5 nm). There
      were no significant differences in variables related to glucose metabolism or in
      serum concentration of free fatty acids or total ketone bodies. CONCLUSIONS:
      These results indicate that DAG oil may be useful for patients who have type 2
      diabetes in the management of obesity and lipid abnormalities.

PMID- 16289978
TI  - Dietary intake of long-chain omega-3 polyunsaturated fatty acids: contribution of
      meat sources.
AB  - OBJECTIVE: We examined the relative contributions of meat and fish to the dietary
      intakes of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFAs). METHODS: A
      database detailing 4550 foods and 4298 recipes recorded in the 1995 Australian
      National Nutrition Survey (NNS95) was updated with new fatty acid compositional
      data then used to determine intakes from 24-h dietary recalls of 13858
      individuals. This approach was validated with food frequency questionnaires from
      8321 of these individuals. RESULTS: Fatty acid intakes were comparable to our
      previous estimates from NNS95 except for LCn3PUFAs, which were considerably
      higher. Mean intakes in adults estimated from the 24-h recalls were 75, 71, and
      100 mg/d for eicosapentaenoic acid, docosapentaenoic acid (DPA), and
      docosahexaenoic acid, respectively, giving a total of 246 mg/d. This is 30%
      greater than our previously published estimate of LCn3PUFA intake, the difference
      being attributable to inaccuracies in pre-existing data on the fatty acid
      composition of certain foods, particularly the DPA content of meats. We estimate
      that 43% of the LCn3PUFAs consumed by adults in the NNS95 survey originated from
      meat, poultry, and game compared with 48% from fish and seafood. Steak and kidney
      pies and other meat-containing cereal-based products accounted for an additional
      4%. Beef and lamb contributed 28% of the total LCn3PUFA intake, whereas pork and
      poultry contributed 4% and 10%, respectively. Food frequency questionnaires
      produced similar results. CONCLUSION: Meat is a major source of LCn3PUFA,
      particularly DPA, for most Australians. When DPA is included in the definition of
      LCn3PUFAs, almost half the average adult intake of LCn3PUFA appears to originate
      from meat sources.

PMID- 16289979
TI  - Effects of diacylglycerol on postprandial energy expenditure and respiratory
      quotient in healthy subjects.
AB  - OBJECTIVE: This study examined the effects of a diacylglycerol (DAG)-containing
      diet on postprandial energy expenditure and respiratory quotient. METHODS: A
      randomized, double-blind, crossover, placebo-controlled study with a washout
      period was performed in 13 healthy male subjects. A 4240-kJ diet containing 30 g
      of triacylglycerol (TAG) or DAG (TAG meal or DAG meal, containing 34.5% lipids,
      52.1% carbohydrates, and 14.1% proteins) was administered after a fasting period
      of 15 to 16 h. Breath and serum were analyzed for up to 5 h after ingestion of
      the meal. RESULTS: The amount of change in energy expenditure 3 h after loading
      with the DAG meal tended to be higher than that after loading with the TAG meal
      (P < 0.1). Changes in respiratory quotient 2 and 5 h after loading with the DAG
      meal were significantly lower than those after loading with the TAG meal,
      suggesting high lipid oxidation activity after the meal. The serum insulin level
      0.5 h after loading with the DAG meal was significantly lower than that after
      loading with the TAG meal. This result suggests that there is a smaller stimulus
      in the direction of fat storage after loading with the DAG meal. CONCLUSIONS:
      Compared with the TAG-containing meal, the DAG-containing meal tended to produce
      a higher postprandial energy expenditure and a significantly lower postprandial
      respiratory quotient. These results suggest that the DAG-containing meal has high
      postprandial lipid oxidation activity and a potential effect on high diet-induced
      thermogenesis.

PMID- 16289980
TI  - Inhaled fluticasone propionate is effective as well as oral prednisone in
      reducing sputum eosinophilia during exacerbations of asthma which do not require
      hospitalization.
AB  - The aim of this study was to evaluate whether fluticasone propionate (FP) is
      effective as well as prednisone (P) in reducing sputum eosinophilia and in
      improving airway obstruction due to asthma exacerbations not requiring
      hospitalization. We measured, in a parallel-group, double-blind double-dummy,
      randomized study, sputum and blood inflammatory cell counts and soluble mediators
      in 37 asthmatic subjects during a spontaneous exacerbation of asthma (Visit 1)
      and after a 2 week (Visit 2) treatment with inhaled FP (1000microg bid) (Group A,
      n=18) or a reducing course of oral P (Group B, n=19). Asthma exacerbation was
      accompanied by sputum eosinophilia (eosinophils >2%) in almost all patients
      (95%). FP improved FEV(1) (from 53.9%+/-16.8 at Visit 1 to 76.4%+/-21.2 at Visit
      2, p=0.0001) and reduced the percentage of sputum eosinophils (from 38%[0-78] to
      3%[1-31, p=0.0008) as well as oral P (FEV(1): from 51.5%+/-14.4 to 83.6%+/-21.1,
      p=0.0001; sputum eosinophils: from 52%[1-96] to 11%[0-64], p=0.0003). At Visit 2,
      sputum eosinophils were significantly lower in Group A than in Group B. P but not
      FP induced significant decrease in blood and sputum ECP. Oxygen saturation, PEF
      variability, symptom score and use of rescue medication similarly improved in
      both groups. We conclude that FP is effective at least as well as P in reducing
      sputum eosinophilia and in improving airway obstruction due to asthma
      exacerbation. However, the cost/effectiveness ratio of this option should be
      further evaluated.

PMID- 16289981
TI  - Exceptional total and functional yields of the human adenosine (A2a) receptor
      expressed in the yeast Saccharomyces cerevisiae.
AB  - The yeast Saccharomyces cerevisiae was used to express a medically relevant G
      protein coupled receptor (GPCR), the human adenosine (A2a) receptor, with a C
      terminal green fluorescent protein (GFP) fusion tag. In prior studies, we
      established an expression system for A2a-GFP. Here, we quantified the total A2a
      GFP expression levels by correlating GFP levels as detected by fluorescence and
      densitometry to A2a-GFP molecules overexpressed in the system. We also quantified
      A2a-GFP functional levels by classical radioligand binding assays. Approximately,
      120,000 functional A2a-GFP molecules per cell were present on the plasma membrane
      as determined by radioligand binding. Using whole cell GFP fluorescence, 340,000
      A2a-GFP molecules per cell were detected; approximately 70% of those molecules
      were plasma membrane localized, as determined by using confocal microscopy
      analysis. These results show that a significant portion of the total expressed
      protein is functional. In addition, the quick and inexpensive whole cell
      fluorescence appears to provide a good approximation of functional receptor
      numbers for this case. Importantly, the amount of functionally expressed A2a-GFP
      per culture ( approximately 4 mg/L) is among the highest reported for any GPCR in
      any expression system.

PMID- 16289982
TI  - High levels of protein expression using different mammalian CMV promoters in
      several cell lines.
AB  - With the recent completion of the human genome sequencing project, scientists are
      faced with the daunting challenge of deciphering the function of these newly
      found genes quickly and efficiently. Equally as important is to produce milligram
      quantities of the therapeutically relevant gene products as quickly as possible.
      Mammalian expression systems provide many advantages to aid in this task.
      Mammalian cell lines have the capacity for proper post-translational
      modifications including proper protein folding and glycosylation. In response to
      the needs described above, we investigated the protein expression levels driven
      by the human CMV in the presence or absence of intron A, the mouse and rat CMV
      promoters with intron A, and the MPSV promoter in plasmid expression vectors. We
      evaluated the different promoters using an in-house plasmid vector backbone. The
      protein expression levels of four genes of interest driven by these promoters
      were evaluated in HEK293EBNA and CHO-K1 cells. Stable and transient transfected
      cells were utilized. In general, the full-length human CMV, in the presence of
      intron A, gave the highest levels of protein expression in transient
      transfections in both cell lines. However, the MPSV promoter resulted in the
      highest levels of stable protein expression in CHO-K1 cells. Using the CMV driven
      constitutive promoters in the presence of intron A, we have been able to generate
      >10 microg/ml of recombinant protein using transient transfections.

PMID- 16289983
TI  - Large-scale preparation of biologically active mouse and rat leptins and their
      L39A/D40A/F41A muteins which act as potent antagonists.
AB  - Expression plasmids encoding mouse and rat leptins and their L39A/D40A/F41A
      muteins were prepared. The proteins were expressed in Escherichia coli, refolded
      and purified to homogeneity, yielding electrophoretically pure, over 98%
      monomeric protein. Circular dichroism (CD) analysis revealed that the mutations
      hardly affect the leptins' secondary structure, and they were similar to
      previously reported CD spectra for human leptin. Both mouse and rat leptins were
      biologically active in promoting proliferation in BAF/3 cells stably transfected
      with the long form of human leptin receptor. The mutations did not change the
      binding properties to BAF/3 cells as compared, respectively, to non-mutated
      mouse, rat or human leptins, or their ability to form 1:1 complexes with the
      leptin-binding domain of chicken leptin receptor. In contrast, their biological
      activity, tested in a BAF/3 proliferation assay, was abolished and both became
      potent antagonists. As the LDF (amino acids 39-41) sequence is preserved in all
      known leptins, the present results substantiate the hypothesis that this sequence
      plays a pivotal role in leptins' site III and that interaction of leptin with its
      receptors resembles the corresponding interactions of interleukin-6 and
      granulocyte colony-stimulating factor their receptors.

PMID- 16289984
TI  - Effect of lipid-containing, positively charged nanoemulsions on skin hydration,
      elasticity and erythema--an in vivo study.
AB  - Dry skin and other skin disorders such as atopic dermatitis are characterized by
      impaired stratum corneum (SC) barrier function and by an increase in
      transepidermal water loss (TEWL) leading to a decrease in skin hydration. The
      possibility that dermatological and cosmetic products containing SC lipids could
      play a part in the restoration of disturbed skin barrier function is of great
      interest in the field of dermatology and cosmetics. The aim of the present study
      was to evaluate the effect of positively charged oil/water nanoemulsions (PN)
      containing ceramide 3B and naturally found SC lipids (PNSC) such as ceramide 3,
      cholesterol, and palmitic acid on skin hydration, elasticity, and erythema.
      Creams of PNSC were compared to PN creams, to creams with negatively charged o/w
      nanoemulsion and SC lipids (NNSC) and to Physiogel cream, a SC lipid containing
      formulation, which is already on the market. The formulations (PN, PNSC, and
      NNSC) were prepared by high-pressure homogenization. After adding Carbopol 940 as
      thickener, particle size and stability of the creams were not significantly
      changed compared to the nanoemulsions. The studies were carried out on three
      groups, each with 14 healthy female test subjects between 25 and 50 years of age,
      using Corneometer 825, Cutometer SEM 575 and Mexameter 18 for measurements of
      skin hydration, elasticity, and erythema of the skin, respectively. The creams
      were applied regularly and well tolerated throughout the study. All formulations
      increased skin hydration and elasticity. There was no significant difference
      between PNSC and Physiogel. However, PNSC was significantly more effective in
      increasing skin hydration and elasticity than PN and NNSC indicating that
      phytosphingosine inducing the positive charge, SC lipids and ceramide 3B are
      crucial for the enhanced effect on skin hydration and viscoelasticity.

PMID- 16289985
TI  - LC/MS/MS quantitation assay for pharmacokinetics of naringenin and double peaks
      phenomenon in rats plasma.
AB  - A highly sensitive and specific electrospray ionization (ESI) liquid
      chromatography-tandem mass spectrometry (LC/MS/MS) method for quantitation of
      naringenin (NAR) and an explanation for the double peaks phenomenon was developed
      and validated. NAR was extracted from rat plasma and tissues along with the
      internal standard (IS), hesperidin, with ethyl acetate. The analytes were
      analyzed in the multiple-reaction-monitoring (MRM) mode as the precursor/product
      ion pair of m/z 273.4/151.3 for NAR and m/z 611.5/303.3 for the IS. The assay was
      linear over the concentration range of 5-2500 ng/mL. The lower limit
      quantification was 5 ng/mL, available for plasma pharmacokinetics of NAR in rats.
      Accuracy in within- and between-run precisions showed good reproducibility. When
      NAR was administered orally, only little and predominantly its glucuronidation
      were into circulation in the plasma. There existed double peaks phenomenon in
      plasma concentration-time curve leading to the relatively slow elimination of NAR
      in plasma. The results showed that there was a linear relationship between the
      AUC of total NAR and dosages. And the double peaks are mainly due to
      enterohepatic circulation.

PMID- 16289986
TI  - Preparation and characterization of dehydration-rehydration vesicles loaded with
      aminoglycoside and macrolide antibiotics.
AB  - Enhanced activity of liposomes-encapsulated antibiotics against clinical isolates
      of Pseudomonas aeruginosa has been documented with liposomes of low encapsulation
      efficiency. We sought to construct liposomes with high yield entrapment of
      aminoglycoside and macrolide antibiotics as well as favorable stability in
      storage and physiological conditions. Liposome-entrapped aminoglycosides
      (amikacin, gentamicin, tobramycin) and a macrolide (erythromycin) were prepared
      by a modified dehydration-rehydration vesicles (DRVs) method, and their particle
      size and entrapment efficiency were determined. We studied in vitro stability of
      these vesicles over a 48 h period at 4 and 37 degrees C in phosphate-buffered
      saline (PBS) and in plasma at 37 degrees C. The mean particle size of DRVs loaded
      with antibiotics varied from 163.37+/-38.44 to 259.83+/-11.80 nm with no
      significant difference in regard with the type of the antibiotics encapsulated.
      Encapsulation efficiency of DRVs loaded with amikacin, gentamicin, tobramycin,
      and erythromycin were 29.27+/-1.17, 33+/-0.76, 22.33+/-1.48 and 32.06+/-0.82% of
      initial amount of the drug, respectively. These vesicles were stable regardless
      of the experimental temperature. Indeed, the liposomes retained more than 75% of
      the initially encapsulated drugs for the study period of 48 h. DRVs incubated in
      plasma however, released more antibiotics than those incubated in PBS. In
      conclusion, using this modified DRV method, we obtained small sized vesicles with
      high yield entrapment for aminoglycoside and macrolide antibiotics. The technique
      may be utilized to overcome the low encapsulation efficiency associated with
      aminoglycoside and macrolide antibiotics.

PMID- 16289987
TI  - Side-to-side differences in cortical bone mineral density of tibiae in young male
      athletes.
AB  - The importance of physical activity in the development and maintenance of bone
      mineral density (BMD) is widely accepted. However, the effects on cortical BMD
      have not been clarified in detail. The present study examined bilateral
      asymmetries in cortical BMD of the tibia using peripheral quantitative computed
      tomography. Subjects comprised 37 young male athletes and 57 controls (age range,
      18-28 years). BMD and geometrical indices were determined in bilateral tibiae.
      Cortical and trabecular BMD were calculated at the diaphysis and distal
      metaphysis, respectively. Cortical width, periosteal cross-sectional area, and
      cross-sectional moment of inertia were calculated using tomographic data of the
      tibial diaphysis. In athletes, the non-dominant leg showed greater cortical BMD
      than the dominant leg (mean difference, 5.42%; P < 0.0001). Cortical width and
      moment of inertia were also greater in the non-dominant leg. Periosteal area
      displayed no significant difference between legs. The control group exhibited
      similar results except for cortical BMD. No differences in trabecular BMD were
      noted between legs in either athletes or controls. These results implies the
      existence of mechanisms for the mechanical adaptation of cortical BMD. Dominant
      leg is used for mobility or manipulation whereas the non-dominant leg contributes
      to support the actions of the dominant leg. Loading differences in bilateral legs
      in young athletes might affect the remodeling rate leading to the side-to-side
      differences in cortical BMD.

PMID- 16289988
TI  - Characterization of oligosaccharides in milk of a mink, Mustela vison.
AB  - Carbohydrates were extracted from a sample of milk from a mink, Mustela vison
      (Family Mustelidae). Free neutral and acidic oligosaccharides were isolated from
      the carbohydrate fraction and their chemical structures were compared with those
      of white-nosed coati (Nasua narica, Procyonidae) and harbour seal (Phoca
      vitulina, Phocidae) that we had studied previously. The ratio of free lactose to
      milk oligosaccharides was similar to that in milk of the white-nosed coati; in
      both species, this ratio was much lower than that in the milk of most eutherians.
      The neutral oligosaccharides of mink milk had alpha(1-3)-linked Gal or alpha(1-2)
      linked Fuc residues at their non-reducing ends, as in the neutral
      oligosaccharides of white-nosed coati milk. Some of the neutral and acidic
      oligosaccharides, determined here, had been found also in harbour seal milk, but
      the harbour seal oligosaccharides did not contain alpha(1-3)-linked Gal residues.

PMID- 16289989
TI  - trans-4-(Aminomethyl)cyclohexane carboxylic acid methylamide (t-AMCHA
      methylamide) inhibits the physical interaction between urokinase-type plasminogen
      activator and stratum corneum, and accelerates the recovery of barrier function.

PMID- 16289990
TI  - Apical dendrite activity in cognition and consciousness.
AB  - The ongoing steady nature of consciousness in everyday life implies that the
      underlying neural activity possesses a high level of stability. The prolonged
      cognitive events of sustained attention, imagery, and working memory also imply
      high stability of underlying neural activity. This paper proposes that
      stabilization of neural activity is produced by apical dendrite activity in
      pyramidal neurons within recurrent corticothalamic circuits, and proposes that
      the wave activities of apical dendrites that stabilize ongoing activity
      constitute the subjective impressions of an attended object and the entire
      sensory background. The cortical minicolumn, as the functional unit of the
      cortex, is separated into an axis consisting of layer 5 pyramidal neurons and a
      surrounding shell consisting of layer 2/3 pyramidal neurons. It is proposed that
      apical dendrites of the axis generate sensory impressions, and basal dendrites of
      the shell process the brief-lasting input-output identifications of objects that
      give rise to ideas.

PMID- 16289991
TI  - Unconscious symmetrical inferences: A role of consciousness in event integration.
AB  - Explicit and implicit learning have been attributed to different learning
      processes that create different types of knowledge structures. Consistent with
      that claim, our study provides evidence that people integrate stimulus events
      differently when consciously aware versus unaware of the relationship between the
      events. In a first, acquisition phase participants sorted words into two
      categories (A and B), which were fully predicted by task-irrelevant primes-the
      labels of two other, semantically unrelated categories (C and D). In a second,
      test phase participants performed a lexical decision task, in which all word
      stimuli stemmed from the previous prime categories (C and D) and the (now
      nonpredictive) primes were the labels of the previous target categories (A and
      B). Reliable priming effects in the second phase demonstrated that bidirectional
      associations between the respective categories had been formed in the acquisition
      phase (A<-->C and B<-->D), but these effects were found only in participants that
      were unaware of the relationship between the categories! We suggest that
      unconscious, implicit learning of event relationships results in the rather
      unsophisticated integration (i.e., bidirectional association) of the underlying
      event representations, whereas explicit learning takes the meaning of the order
      of the events into account, and thus creates unidirectional associations.

PMID- 16289992
TI  - Aspects of the unity of consciousness and everyday memory failures.
AB  - We argue that analyzing everyday memory failures in terms of the "unity of
      consciousness" can elucidate the bases of such failures. A perfect unity amongst
      one's mental states is rare. In extreme cases the unity of consciousness can
      breakdown in dramatic fashion (e.g., in Dissociative Identity Disorder), but such
      breakdowns also occur in less dramatic ways that affect us in everyday life. For
      example, disruptions in the unity of consciousness can result in everyday memory
      failures, such as forgetting to put on a tie for an important formal meeting.
      After providing some philosophical background into the notions of "unity of
      consciousness" and "functionalism," we offer preliminary analyses of three
      examples of everyday memory failure. We then introduce and develop what we call
      the "unity model" of memory failure and show how it explains the examples. We
      also describe different ways that unity can break down which, in turn, can lead
      to memory failure and inappropriate behavior. We then show how slips of action
      and other kinds of cognitive failures (e.g., memory blocks) differ from everyday
      memory failures. Finally, we examine alternative models (e.g., Absentmindedness
      and Multimodal) arguing that the unity model is preferable, and then show how our
      model is consistent with some experimental results.

PMID- 16289994
TI  - In vitro study of the interaction of polyalkilimide and polyvinyl alcohol
      hydrogels with cells.
AB  - Hydrogels are a class of polymers that in the last decade have had a great
      development and application for soft tissue augmentation, due to their similarity
      to this tissue for their high water content. The in vitro effects of
      polyalkylmide hydrogel (pAI) and polyvinyl alcohol hydrogel (pVOH) on human
      lymphocytes and U937 cells viability, apoptosis and cell shape were investigated.
      Cell viability was always higher than 70%, thus showing the hydrogels were not
      cytotoxic for both cell lines. Some differences were, however, found. At short
      time, lymphocytes were very sensitive to the hydrogels incubation, while at long
      time, U937 cells were the most sensitive cells. Other differences on cell
      viability were related to the time of incubation, to the type of hydrogel and to
      the polymers concentration. Cell viability decreased only at the longest time of
      incubation and with the highest hydrogel concentration. Accordingly, cell death
      by apoptosis increased; necrosis was never observed in the cultures.
      Concentration- and hydrogel-dependent modifications of cell shape (bigger cell
      volume, elongations of cells) were observed in a few percentage of viable cells.
      In conclusion, the very high in vitro degree of biocompatibility shown by both
      hydrogels encourages their use as dermal fillers.

PMID- 16289993
TI  - Gentamicin induced nitric oxide-related oxidative damages on vestibular afferents
      in the guinea pig.
AB  - Gentamicin is a well-known ototoxic aminoglycoside. However, the mechanism
      underlying this ototoxicity remains unclear. One of the mechanisms which may be
      responsible for this ototoxicity is excitotoxic damage to hair cells. The
      overstimulation of the N-methyl-d-aspartate (NMDA) receptors increases the
      production of nitric oxide (NO), which induces oxidative stress on hair cells. In
      order to determine the mechanism underlying this excitotoxicity, we treated
      guinea pigs with gentamicin by placing gentamicin (0.5 mg) pellets into a round
      window niche. After the sacrifice of the animals, which occurred at 3, 7 and 14
      days after the treatment, the numbers of hair cells in the animals were counted
      with a scanning electron microscope. We then performed immunostaining using
      neuronal nitric oxide synthase (nNOS), inducible NOS (iNOS) and nitrotyrosine
      antibodies. The number of hair cells in the animals was found to decrease
      significantly after 7 days. nNOS and iNOS expression levels were observed to have
      increased 3 days after treatment. Nitrotyrosine was expressed primarily at the
      calyceal afferents of the type I hair cells 3 days after treatment. Terminal
      deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining
      revealed positive hair cells 3 days after treatment. Our results suggest that
      inner ear treatment with gentamicin may upregulate nNOS and iNOS to induce
      oxidative stress in the calyceal afferents of type I hair cells, via nitric oxide
      overproduction.

PMID- 16289995
TI  - Characterization of vitellin from the ovaries of the banana shrimp Litopenaeus
      merguiensis.
AB  - Vitellin (Vt) was purified from ovary extracts of mature females of the banana
      shrimp Litopenaeus merguiensis using DEAE-Sephacel and Superdex 200 columns.
      Native Vt had an apparent molecular mass of 398 kDa as determined by native PAGE
      and by gel filtration chromatography. Under reducing and denaturing conditions
      (SDS-PAGE), Vt is composed of two major subunits of 87 and 78 kDa, although some
      faint bands were also detected. The N-terminal 10 amino acids sequence of the 78
      kDa subunit is identical to that of Litopenaeus vannamei Vt and very similar to
      that of Litopenaeus japonicus vitellogenin (Vg) as well as Litopenaeus
      semisulcatus Vt, with an identity of 89%. Anti-Vt polyclonal antibody raised
      against purified Vt shows a high specificity with only ovarian Vt and hemolymph
      Vg of vitellogenic shrimps in double immunodiffusion and Western blot assays. Vg
      and Vt concentrations in hemolymph, hepatopancreas and ovaries were measured by
      ELISA. Vg concentrations increased in the hemolymph in the early stages of
      ovarian development and declined in the maturation stages. As there were
      undetectable concentrations of Vg in the hepatopancreas while an elevation of Vg
      levels occurred in the hemolymph, during the time that Vt was accumulating in the
      ovaries during oogenesis, this would suggest that the contribution of Vg
      synthesized by the hepatopancreas only might be not sufficient for adequate
      development of the oocytes in the banana shrimp L. merguiensis during
      vitellogenesis.

PMID- 16289996
TI  - Development of novel strategies to control foot-and-mouth disease: marker
      vaccines and antivirals.
AB  - Foot-and-mouth disease (FMD) is economically the most important viral-induced
      livestock disease worldwide. The disease is highly contagious and FMD virus
      (FMDV) replicates and spreads extremely rapidly. Outbreaks in previously FMD-free
      countries, including Taiwan, the United Kingdom, and Uruguay, and the potential
      use of FMDV by terrorist groups have demonstrated the vulnerability of countries
      and the need to develop control strategies that can rapidly inhibit or limit
      disease spread. The current vaccine, an inactivated whole virus preparation, has
      a number of limitations for use in outbreaks in disease-free countries. We have
      developed an alternative approach using a genetically engineered FMD subunit
      vaccine that only contains the portions of the viral genome required for virus
      capsid assembly and lacks the coding region for most of the viral nonstructural
      (NS) proteins including the highly immunogenic 3D protein. Thus, animals
      inoculated with this marker vaccine can readily be differentiated from infected
      animals using diagnostic assays employing the NS proteins not present in the
      vaccine and production of this vaccine, which does not contain infectious FMDV,
      does not require expensive high-containment manufacturing facilities. One
      inoculation of this subunit vaccine delivered in a replication-defective human
      adenovirus vector can induce rapid, within 7 days, and relatively long-lasting
      protection in swine. Similarly cattle inoculated with one dose of this
      recombinant vector are rapidly protected from direct and contact exposure to
      virulent virus. Furthermore, cattle given two doses of this vaccine developed
      high levels of FMDV-specific neutralizing antibodies, but did not develop
      antibodies against viral NS proteins demonstrating the ability of FMD subunit
      vaccinated animals to be differentiated from infected animals. To stimulate early
      protection prior to the vaccine-induced adaptive immune response we inoculated
      swine with the antiviral agent, type I interferon, and induced complete
      protection within 1 day. Protection can last for 3-5 days. The combination of the
      FMD marker vaccine and type I interferon can induce immediate, within 1 day, and
      long-lasting protection against FMD. Thus, this combination approach successfully
      addresses a number of concerns of FMD-free countries with the current disease
      control plan. By rapidly limiting virus replication and spread this strategy may
      reduce the number of animals that need to be slaughtered during an outbreak.

PMID- 16289997
TI  - Regulation of immunologicals in the European union: current and emerging issues.

PMID- 16289998
TI  - The neural basis of temporal auditory discrimination.
AB  - When two identical stimuli, such as a pair of clicks, are presented with a
      sufficiently long time-interval between them they are readily perceived as two
      separate events. However, as they are presented progressively closer together,
      there comes a point when the two separate stimuli are perceived as one. This
      phenomenon applies not only to hearing but also to other sensory modalities.
      Damage to the basal ganglia disturbs this type of temporal discrimination
      irrespective of sensory modality, suggesting a multimodal process is involved.
      Our aim was to study the neural substrate of auditory temporal discrimination in
      healthy subjects and to compare it with structures previously associated with
      analogous tactile temporal discrimination. During fMRI scanning, paired-clicks
      separated by variable inter-stimulus intervals (1-50 ms) were delivered
      binaurally, with different intensities delivered to each ear, yielding a
      lateralised auditory percept. Subjects were required (a) to report whether they
      heard one or two stimuli (TD: temporal discrimination); or (b) to report whether
      the stimuli were located on the right or left side of the head mid-line (SD:
      spatial discrimination); or (c) simply to detect the presence of an auditory
      stimulus (control task). Our results showed that both types of auditory
      discrimination (TD and SD) compared to simple detection activated a network of
      brain areas including regions of prefrontal cortex and basal ganglia. Critically,
      two clusters in pre-SMA and the anterior cingulate cortex were specifically
      activated by TD. Furthermore, these clusters overlap with regions activated for
      similar judgments in the tactile modality suggesting that they fulfill a
      multimodal function in the temporal processing of sensory events.

PMID- 16289999
TI  - Acidosis, lactate, electrolytes, muscle enzymes, and other factors in the blood
      of Sus scrofa following repeated TASER exposures.
AB  - Repeated exposure to electro-muscular incapacitating devices could result in
      repetitive, sustained muscle contraction, with little or no muscle recovery
      period. Therefore, rhabdomyolysis and other physiological responses, including
      acidosis, hyperkalaemia, and altered levels of muscle enzymes in the blood, would
      be likely to occur. Experiments were performed to investigate effects of repeated
      exposures of TASER International's Advanced TASER X26 on muscle contraction and
      resultant changes in blood factors in an anaesthetized swine model. A total of 10
      animals were used. Six swine were exposed for 5 s, followed by a 5-s period of no
      exposure, repeatedly for 3 min. (In five of the animals, after a 1-h delay, a
      second 3-min exposure period was added.) The remaining four animals were used for
      an additional pilot study. All four limbs of each animal exhibited contraction
      even though the electrodes were positioned in areas at some distances from the
      limbs. The degree of muscle contraction generated during the second exposure
      period was significantly lower than that in the first exposure series. This
      finding was consistent with previous studies showing that prolonged activity in
      skeletal muscle will eventually result in a decline of force production. There
      were some similarities in blood sample changes in the current experiments with
      previous studies of muscular exercise. Thus problems concerning biological
      effects of repeated TASER exposures may be related, not directly to the "electric
      output" per se, but rather to the resulting contraction of muscles (and related
      interruption of respiration) and subsequent sequelae. Transient increases in
      hematocrit, potassium, and sodium were consistent with previous reports in the
      literature dealing with studies of muscle stimulation or exercise. It is doubtful
      that these short-term elevations would have any serious health consequences in a
      healthy individual. Blood pH was significantly decreased for 1h following
      exposure, but subsequently returned toward a normal level. Leg muscle
      contractions and decreases in respiration each appeared to contribute to the
      acidosis. Lactate was highly elevated, with a slow return (time course greater
      than 1 h) to baseline. Other investigators have reported profound metabolic
      acidosis during restraint-associated cardiac arrest. Since restraint often occurs
      immediately after TASER exposure, this issue should be considered in further
      development of deployment concepts. On the basis of the results of the current
      studies, the repeated use of electro-muscular incapacitating devices in a short
      period of time is, at least, feasible, with the caveat that some medical
      monitoring of subjects may be required (to observe factors such as lactate and
      acidosis).

PMID- 16290001
TI  - Value of preoperative serum CA125 in early-stage adenocarcinoma of the uterine
      cervix without pelvic lymph node metastasis.
AB  - OBJECTIVE: This investigation attempted to clarify the value of preoperative
      serum CA125 in predicting histopathological prognostic factors for early-stage
      cervical adenocarcinoma without lymph node metastasis. METHODS: This study
      initially surveyed 163 patients with clinical stage Ib or IIa cervical
      adenocarcinoma treated with radical hysterectomy and pelvic lymphadenectomy. Of
      the 163 patients, 116 had preoperative serum CA125 levels, and 14 had pelvic
      lymph node metastasis. The investigation group comprised 102 lymph node-negative
      patients. RESULTS: A cutoff value of 26 U/ml was obtained after the discriminant
      function analysis for identifying patients with positive lymph vascular space
      invasion (LVSI) or depth of stromal invasion > or =2/3 thickness. Multivariate
      analysis revealed that among the preoperative clinicopathological variables,
      including age, tumor size, parametrial invasion, and CA125 level, raised CA125
      most significantly influenced the assessment of the LVSI (P = 0.040) and depth of
      cervical stromal invasion (P = 0.002). CONCLUSIONS: In early-stage cervical
      adenocarcinoma with negative pelvic lymph node metastasis, preoperative serum
      CA125 levels at the cutoff value of 26 U/ml impacted the determination of the
      poor histopathological prognostic factors.

PMID- 16290000
TI  - PTEN expression in clear cell adenocarcinoma of the ovary.
AB  - OBJECTIVES: In this study, we analyzed the PTEN expression in a large collection
      of clear cell adenocarcinomas of the ovary. Furthermore, we analyzed the
      expression of cyclin D1 and p27, and investigated the correlation among all these
      variables. METHODS: Totally, 40 clear cell adenocarcinomas were included in this
      study. The protein expression of PTEN, cyclin D1 and p27 was investigated by
      immunohistochemistry. RESULTS: Of 40 clear cell adenocarcinomas, 15 (37.5%) lost
      all PTEN immunoreactivity. There was no significant correlation between PTEN
      expression and clinical stage. Cyclin D1 expression and loss of p27 expression
      were detected in 16/40 (40.0%) and 14/40 (35.0%) clear cell adenocarcinoma cases.
      There was no significant correlation between PTEN expression and cyclin D1 or p27
      protein expression. CONCLUSIONS: Loss of PTEN expression is relatively common and
      both cyclin D1 and p27 expressions are not related with PTEN inactivation in
      clear cell adenocarcinoma of the ovary.

PMID- 16290002
TI  - The prevalence of HR-HPV DNA in ASC-US Pap smears: A military population study.
AB  - OBJECTIVE: To determine the prevalence of HR-HPV DNA in ASC-US Pap smears
      following implementation of the Bethesda 2001 classification system. METHODS: A
      computer database of Pap smears obtained within Department of the Army medical
      facilities was queried for the study period August 2002 to June 2004. All ASC-US
      Pap smears that underwent reflex testing for HR-HPV DNA were included. Additional
      clinical and demographic data were obtained from facilities within the US
      northeast region to evaluate the differences in ASC-US and SIL rates between the
      current and former Bethesda classification systems. RESULTS: 550,000 Pap smears
      were collected during the study period. The HR-HPV prevalence was 40.8% (95%
      confidence interval [CI] = 40.3 to 41.3) among 40,870 patients with ASC-US Pap
      smears. Within the northeast region, the HR-HPV prevalence in ASC-US Pap smears
      decreased from 61.2% (95% CI = 57.4 to 64.8%) in patients 18-22 years old to
      24.9% (95% CI = 23.1 to 26.8%) in patients age 29 and older. When comparing the
      two classification systems, significant increases in both ASC-H and SIL and
      decreases in ASC-US were appreciated after the institution of Bethesda system
      2001. CONCLUSION: In our large, diverse cohort, the implementation of the
      Bethesda II system has resulted in a decrease in ASC-US Pap smear results.
      Additionally, the prevalence of HR-HPV in the ASC-US population was 40.8%,
      significantly lower than the rate noted in the ALTS trial under the Bethesda I
      classification system.

PMID- 16290003
TI  - Extended tetrahydrobiopterin loading test in the diagnosis of cofactor-responsive
      phenylketonuria: a pilot study.
AB  - Patients with tetrahydrobiopterin (BH4)-responsive phenylalanine hydroxylase
      (PAH) deficiency may benefit from BH4 therapy instead or in addition to the low
      phenylalanine diet. Different loading test protocols are currently used to detect
      these patients. As a consequence, data on the rate of BH4-responsiveness within
      patients with mild phenylketonuria (PKU) and/or more severe phenotypes show high
      variation and a more sensitive and standardised BH4 loading test protocol needs
      to be defined. We modified the current standard BH4 loading test (20 mg/kg) to a
      second administration of 20 mg/kg after 24 h and extended blood sampling to 48 h
      in 24 patients with PAH deficiency. Using this extended loading test (2 x 20 mg
      BH4/kg), the rate of BH4-responsiveness was calculated at 8, 24, and 48 h after
      BH4 administration. We defined three groups of patients: "rapid responders" in
      10/24 patients (4 mild HPA, 2 mild PKU, 2 moderate PKU, and 2 classic PKU),
      "moderate responders" in 4/24 patients (4 classic PKU), and "slow responder" in
      4/24 patients (4 mild PKU). Six out of 24 patients (1 mild HPA, 1 moderate PKU,
      and 4 classic PKU) were found to be "non-responder." Individual phenylalanine
      profiles show variations in responsiveness at different time points and sampling
      over 48 h was more informative than over 24h in patients with mild and moderate
      PKU compared to mild HPA. Analysis of BH4 loading tests in 209 patients with the
      standard BH4 loading test protocol confirms only minor importance of the 24 h
      response: the rate of responsiveness to BH4 after 24 h was shown to be equal to
      or even lower than after 8h among most phenotypes. However, extension of the BH4
      loading test to 48 h and repeated BH4 administration seems to be useful to detect
      BH4-responsiveness in more severe phenotypes and allows detecting "slow
      responders" who may benefit from BH4 therapy.

PMID- 16290004
TI  - Stimulation of hepatic phenylalanine hydroxylase activity but not Pah-mRNA
      expression upon oral loading of tetrahydrobiopterin in normal mice.
AB  - Tetrahydrobiopterin (BH4) supplementation in patients with BH4-responsive
      phenylalanine hydroxylase (PAH) deficiency is an alternative to low-phenylalanine
      diet. To further investigate hepatic BH4-responsiveness, oral administration of
      50 mg BH4/kg/day for 5 weeks was performed in wild-type mice. We observed a 2
      fold increase in PAH protein by quantitative Western blot analysis and a 1.7-fold
      increase in enzyme activity, but no change in Pah-mRNA expression by quantitative
      real-time PCR analysis in treated mice compared to controls. Our findings support
      the proposed chemical-chaperone effect of BH4 to protect PAH.

PMID- 16290005
TI  - Single step protocol to purify recombinant proteins with low endotoxin contents.
AB  - Endotoxin is an unwanted by product of recombinant proteins purified from
      Escherichia coli. The inherent toxicity of endotoxins makes their removal an
      important step for the proteins' application in several biological assays and for
      safe parenteral administration. The method described in this paper is a one-step
      protocol which is effective at removing tightly bound endotoxin from over
      expressed tagged proteins in E. coli. We combined affinity chromatography with a
      non-ionic detergent washing step, to remove most of the endotoxin contaminants
      from the end product. An endotoxin reduction of less than 4 to 0.2 EU mg(-1) was
      achieved with protein recovery close to a yield 100%. As this new protocol
      requires only one step to simultaneously purify tagged proteins and eliminate
      endotoxins, it represents a substantial advantage in time, effort, and expense.

PMID- 16290006
TI  - Challenges in the expression of disulfide bonded, threonine-rich antifreeze
      proteins in bacteria and yeast.
AB  - Certain freeze-intolerant insects produce antifreeze proteins (AFPs) during
      overwintering including the spruce budworm (Choristoneura fumiferana) and yellow
      mealworm (Tenebrio molitor) AFP gene families. However, only a few of the
      isoforms, encoded by their multiple-copy gene families, have been characterized.
      When expressed in bacterial systems the insect AFPs have to be denatured and
      refolded in vitro, a procedure that is not uniformly successful, presumably due
      to the beta-helix structure and the requirement for disulfide bonds. In an
      attempt to overcome these difficulties, bacterial vectors and hosts that have
      been developed to produce soluble, folded proteins, as well as a yeast expression
      system (Pichia pastoris) were employed. Bacterial expression resulted in low
      quantities of active recombinant protein for certain isoforms. In contrast, both
      small and large-scale fermentation of recombinant AFP in Pichia yielded
      substantial protein production (100 mg/L) but functional ice binding activity of
      protein produced in three different transformed yeast strains (KM71, X33 or
      GS115) was low. Inappropriate O-linked glycosylation of the Thr-rich AFPs
      appeared to be partially reversed by mild chemical deglycosylation, but activity
      remained low. Substantial quantities, as well as activity were recovered when a
      fish AFP, with disulfide bonds, but without potential Thr glycosylation sites was
      expressed in the yeast system.

PMID- 16290007
TI  - Over-expression of a mammalian small conductance calcium-activated K+ channel in
      Pichia pastoris: effects of trafficking signals and subunit fusions.
AB  - Mammalian SK proteins are Ca2+-activated K+ channels, which show a sub-20 pS
      conductance. We have expressed the SK2 variant gene in Pichia pastoris and found
      protein to be produced at considerably higher levels than in brain tissue. The
      channel was correctly folded as evidenced by its high affinity interaction with
      apamin, a specific ligand from bee venom. However, the protein was largely unable
      to reach the plasma membrane, its normal destination, instead remaining in the
      endoplasmic reticulum. Adding a putative translocation sequence altered the
      intracellular distribution significantly with enhanced trafficking out of the
      endoplamic reticulum. Fusion of SK2 with the associated protein calmodulin also
      altered the channel localisation but in a different manner with channels now
      found mainly in transit between endoplasmic reticulum and Golgi compartments.

PMID- 16290009
TI  - Combined hydrophobic-metal binding fusion tags for applications in aqueous two
      phase partitioning.
AB  - In this work, we studied the influence of fusion affinity tags containing both
      hydrophobic and histidines residues on the partitioning of the green fluorescent
      protein, GFPuv, in aqueous two-phase system. The tags were fused to the N
      terminal of GFPuv and tested by immobilized metal affinity partitioning, in a
      PEG/salt system. The presence of both types of residues in the tag increased the
      partitioning greatly. Particularly, four engineered tags (H6, FH6, WH6, and YH6)
      containing a hexa-histidine sequence as well as different hydrophobic residues,
      all increased partitioning more than twice, reaching K values around 20, as
      compared to another construct (His6-GFP) containing an isolated hexa-histidine
      sequence. YH6, also proved be beneficial for protein expression.

PMID- 16290008
TI  - Purification and properties of a novel extra-cellular thermotolerant
      metallolipase of Bacillus coagulans MTCC-6375 isolate.
AB  - A novel extra-cellular lipase from Bacillus coagulans MTCC-6375 was purified 76.4
      fold by DEAE anion exchange and Octyl Sepharose chromatography. The purified
      enzyme was found to be electrophoretically pure by denaturing gel electrophoresis
      and possessed a molecular mass of approximately 103 kDa. The lipase was optimally
      active at 45 degrees C and retained approximately 50% of its original activity
      after 20 min of incubation at 55 degrees C. The enzyme was optimally active at pH
      8.5. Mg2+, Cu2+, Ca2+, Hg2+, Al3+, and Fe3+ at 1mM enhanced hydrolytic activity
      of the lipase. Interestingly, Hg2+ ions resulted in a maximal increase in lipase
      activity but Zn2+ and Co2+ ions showed an antagonistic effect on this enzyme.
      EDTA at 150 mM concentration inhibited the activity of lipase but Hg2+ or Al3+
      (10mM) restored most of the activity of EDTA-quenched lipase. Phenyl methyl
      sulfonyl fluoride (PMSF, 15 mM) decreased 98% of original activity of lipase. The
      lipase was more specific to p-nitrophenyl esters of 8 (pNPC) and 16 (pNPP) carbon
      chain length esters. The lipase had a Vmax and Km of 0.44 mmol mg(-1)min(-1) and
      28 mM for hydrolysis of pNPP, and 0.7 mmol mg(-1)min(-1) and 32 mM for hydrolysis
      of pNPC, respectively.

PMID- 16290010
TI  - Complete, precise, and innocuous loss of multiple introns in the currently
      intronless, active cathepsin L-like genes, and inference from this event.
AB  - Retrotransposition typically generates pseudogenes. Here we demonstrate a
      different fate of the retro-processed genes through a novel mechanism in which
      the retro-processed genes still maintain their sequence intactness and the
      original functions. We show that the shrimp cathepsin L (CatL) gene MeCatL has
      lost all of its five introns. Also, ProEPB, the ancestor of the CatL-like barley
      EPBs and rice REP1, has lost all of its three introns. The multiple introns in a
      gene might have been eliminated simultaneously and precisely at the original
      locus for the CatL-like genes of shrimp, barley, rice, Drosophila, and Theileria.
      We reason that retrotransposition is not responsible for the generation of a
      processed active intronless (PAI) gene when the gene product retains its sequence
      intactness and its original function. We propose that double-strand-break repair
      (DSBR) machinery might play a role in cDNA-mediated homologous recombination
      (cDMHR) that causes the loss of introns. The cDMHR/DSBR pathway is probably a
      fundamental mechanism for intron loss in PAI genes and in some asymmetric-intron
      genes.

PMID- 16290011
TI  - [Hospital hygiene and antibiotherapy counselling: an operational dual solution
      against the spreading of multiresistant bacteria].
AB  - OBJECTIVES: The authors had for aim to show that preventing the diffusion of
      multidrug-resistant organism (MRO) is possible thanks to the coordination of
      recommended preventive actions and the implementation of a sensible anti
      infective prescription policy. They also wanted to highlight the role played by
      the nursing care staff in enforcing recommendations. METHOD: We compared the
      results of two health care facilities having both implemented the same strategy
      aimed at preventing cross-transmission and prescribing anti-infective drugs.
      RESULTS: Audits reported a very variable enforcement of recommendations. The
      results obtained from microbiological monitoring confirmed the essential impact
      of protocol enactment by every team, on the control of MRO diffusion. The
      antibiotherapy specialist has a key role in the suggested strategy, allowing a
      significant decrease in the number of anti-infective prescriptions and a more
      rational use. CONCLUSION: The collaboration of a hygiene specialist with an
      antibiotherapy specialist has proved operational in the fight against MRO
      diffusion, as long as the competences of both specialists are acknowledged and
      their cross-disciplinary activities accepted. For the entire staff, enacting a
      corporate culture is a crucial asset.

PMID- 16290012
TI  - Intracerebroventricular D-Pen2, D-Pen5-enkephalin administration soon after
      stressor imposition influences behavioral responsivity to a subsequent stressor
      encounter in CD-1 mice.
AB  - Endogenous opioid peptide systems diminish stress-induced autonomic nervous
      system, neuroendocrine (hypothalamic-pituitary-adrenal axis) and behavioral
      responses, attenuating a collection of physiological symptoms basic to emotional
      and affective states. Neurogenic stressors may incite specific central changes in
      opioid peptide availability as well as changes in mu and delta-opioid receptor
      function. The present investigation evaluated the proactive influence of an
      intracerebroventricular injection of the opioid receptor agonist D-Pen2, D-Pen5
      enkephalin (DPDPE) (0 microg, 0.005 microg, 1.0 microg or 2.5 microg) on
      locomotor behavior of mice following uncontrollable footshock (Shock) or novel
      shock chamber exposure (No Shock). It was expected that DPDPE administration
      following Shock on Day 1 would restore locomotor activity up to 1 week and
      prevent shock-associated behavior of mice encountering a brief session of
      footshock 18 days later. Exposure to Shock reduced horizontal locomotor and
      vertical locomotor (rearing) activity of mice while 2.5 microg DPDPE restored
      behavior. Eighteen days following Shock and DPDPE challenge, mice were exposed to
      either an abbreviated session of footshock (Mild Stress) or the shock chamber
      (Cues). Mice in the No Shock and Shock groups administered 2.5 microg DPDPE on
      Day 1 did not exhibit any locomotor deficits in response to Mild Stress on Day
      18. Mice in the Shock group administered 0.005 microg DPDPE on Day 1, did not
      exhibit exaggerated rearing deficits following ensuing Mild Stressor encounter
      relative to mice reexposed to Cues on Day 18. Taken together, these data show
      that (a) footshock differentially affects rearing and locomotor activity, (b)
      DPDPE administration increases locomotor activity for up to 1 week following
      footshock and DPDPE administration, (c) reexposure to Mild Stress affects rearing
      and locomotor performance differently depending on previous stressor history and
      DPDPE dose, (d) DPDPE affords long-lasting protection to previously non-stressed
      mice against the deleterious effects of subsequent mild stress on locomotor
      activity, while a low dose of DPDE is sufficient to prevent shock-induced
      sensitization of rearing deficits, 18 days following original stressor and drug
      presentation. Finally, our investigation demonstrates that DPDPE administration
      alters the behavioral impact of future stressful encounters and emphasizes the
      importance of investigating opioid mechanisms in chronic stress disorders.

PMID- 16290013
TI  - A preliminary in vitro study on inducible and constitutive clindamycin resistance
      in Staphylococcus aureus from a South Indian tertiary care hospital.

PMID- 16290014
TI  - Enhancing the etiologic diagnosis of community-acquired pneumonia in adults using
      the urinary antigen assay (Binax NOW).
AB  - OBJECTIVES: Approximately 40% of community-acquired pneumonia (CAP) remains of
      unknown etiology. To improve the rate of detection of the causative microbiologic
      agent, the Binax NOW Streptococcus pneumoniae urinary antigen test (UAT) was
      evaluated. DESIGN: In this prospective study, 67 adults with CAP were compared
      with 81 healthy patients to determine sensitivity and specificity of the UAT and
      its role in improving the etiologic diagnosis of CAP. RESULTS: An etiology could
      be found for 22 patients (33%) using conventional methods (14 S. pneumoniae,
      sensitivity 64.3%, 1/81 positive UAT control urine samples, specificity 98.8%).
      This proportion increased to 33 patients (49%) with the addition of the urinary
      antigen test (p = 0.039). Pneumococcal infection was diagnosed by the UAT in 24%
      of our patients without an etiologic identification by conventional methods.
      CONCLUSIONS: Given its excellent specificity, this test can be considered an
      important tool for detecting S. pneumoniae in CAP of unknown etiology, enabling
      the diagnosis of pneumococcal pneumonia in a quarter of cases.

PMID- 16290015
TI  - Decreased protein C, protein S, and antithrombin levels are predictive of poor
      outcome in Gram-negative sepsis caused by Burkholderia pseudomallei.
AB  - BACKGROUND: Acute septicemic melioidosis is associated with systemic release of
      endotoxin and the proinflammatory cytokines tumor necrosis factor (TNF)-alpha,
      interleukin-1, and interleukin-6. Excessive release of these cytokines may lead
      to endothelial injury, depletion of naturally occurring endothelial modulators,
      microvascular thrombosis, organ failure, and death. METHOD: Plasma samples drawn
      at baseline and after initial antimicrobial therapy in 30 patients with suspected
      acute severe melioidosis were assayed for D-dimer levels, protein C and protein S
      antigen levels, and antithrombin functional activities. RESULTS: Both baseline
      and continued deficiencies of protein C, protein S, and antithrombin were
      statistically associated with a poor outcome by logistic regression. Baseline D
      dimer levels were significantly higher in fatal cases than survivors and
      correlated inversely with protein C and antithrombin, suggesting both increased
      fibrin deposition and fibrinolysis. CONCLUSION: The inflammatory response to
      systemic Burkholderia pseudomallei infection leads to depletion of the natural
      endothelial modulators protein C, protein S, and antithrombin. Both baseline and
      continued deficiency of these endothelial modulators is predictive of poor
      outcome in melioidosis.

PMID- 16290016
TI  - The neural correlates of direct and reflected self-knowledge.
AB  - Socrates said that in order to lead a balanced life one must, "know thyself." In
      two fMRI experiments, the present study examined the mechanisms mediating two
      ways in which the self can be known: through direct appraisals (i.e., an
      individual's own self-beliefs) and reflected appraisals (i.e., an individual's
      perception of how others view him or her). Experiment 1 examined the common and
      distinct neural bases of direct appraisals of the self, close others, and
      normative judgments of trait desirability. All three judgment types activated
      medial prefrontal cortex (MPFC) to a similar degree. Experiment 2 examined the
      common and distinct neural bases of (1) direct appraisals of self, a close other
      or a non-close other, and (2) reflected appraisals made from the perspective of a
      close or a non-close other. Consistent with Experiment 1, all judgment types
      activated MPFC. Direct appraisals of the self as compared to others more strongly
      recruited MPFC and right rostrolateral PFC. Direct appraisals as compared to
      reflected appraisals recruited regions associated with a first-person perspective
      (posterior cingulate), whereas reflected as compared to direct appraisals
      recruited regions associated with emotion and memory (insula, orbitofrontal, and
      temporal cortex). These results support models suggesting that MPFC mediates meta
      cognitive processes that may be recruited for direct and reflected self
      appraisals depending upon the demands of a specific task.

PMID- 16290017
TI  - Left mediotemporal structures mediate the retrieval of episodic autobiographical
      mental images.
AB  - The aim of this functional magnetic resonance imaging (fMRI) study was to
      investigate the neuroanatomical substrates associated with the process of mental
      generation of specific (i.e., exemplar) and episodic autobiographical (i.e., an
      image of a unique life episode connected with an object) images. The fMRI
      paradigm in this experiment included a non-image generation baseline and two
      activation conditions requiring the generation of either specific or episodic
      autobiographical images. Image generation times and brain activation were
      recorded. Behavioral results showed that generating specific mental images took
      significantly less than generating episodic autobiographical images. Individuals
      generated specific images that were well distinct from the episodic
      autobiographical ones, semantic in nature without an episodic reference. Episodic
      autobiographical images did not show a significant bias towards preferential
      retrieval from any particular life period but were retrieved from across the
      entire life span. Conjunction analysis of the fMRI data showed that the two image
      generation conditions significantly activated a common set of neural structures,
      including mediofrontal areas. This shared pattern of activation might be the
      result of an underlying similar format and characteristics (e.g., richness in
      details) between the two types of images and might reflect the involvement of
      similar cognitive processes. Distinct patterns of significant activation were
      also present. Activation in the right parietal regions, cuneus, precuneus and
      left temporal regions was associated solely with the generation of specific
      images. Regions more specifically devoted to episodic memory retrieval and
      imagery, such as the left parahippocampal gyrus and precuneus, and the posterior
      cingulate cortex bilaterally, were significantly activated exclusively by the
      generation of episodic autobiographical images.

PMID- 16290018
TI  - Correlating the alpha rhythm to BOLD using simultaneous EEG/fMRI: inter-subject
      variability.
AB  - Simultaneous recording of electroencephalogram/functional magnetic resonance
      images (EEG/fMRI) was applied to identify blood oxygenation level-dependent
      (BOLD) changes associated with spontaneous variations of the alpha rhythm, which
      is considered the hallmark of the brain resting state. The analysis was focused
      on inter-subject variability associated with the resting state. Data from 7
      normal subjects are presented. Confirming earlier findings, three subjects showed
      a negative correlation between the BOLD signal and the average power time series
      within the alpha band (8--12 Hz) in extensive areas of the occipital, parietal
      and frontal lobes. In small thalamic areas, the BOLD signal was positively
      correlated with the alpha power. For subjects 3 and 4, who displayed two
      different states during the data acquisition time, it was shown that the
      corresponding correlation patterns were different, thus demonstrating the state
      dependency of the results. In subject 5, the changes in BOLD were observed mainly
      in the frontal and temporal lobes. Subject 6 only showed positive correlations,
      thus contradicting the negative BOLD alpha power cortical correlations that were
      found in most subjects. Results suggest that the resting state varies over
      subjects and, sometimes, even within one subject. As the resting state plays an
      important role in many fMRI experiments, the inter-subject variability of this
      state should be addressed when comparing fMRI results from different subjects.

PMID- 16290019
TI  - Do astrocytes contribute to excitation underlying seizures?
AB  - Synchronous neuronal activity during seizures is thought to arise from an
      entirely neuronal origin. A recent study by Tian et al. suggests that by
      releasing glutamate, astrocytes contribute to the neuronal depolarizations
      underling epilepsy. Treatment of hippocampal and cortical tissue with compounds
      that induce seizures was shown to excite astrocytes directly through a pathway
      that stimulates the release of glial glutamate. Anticonvulsants reduce the
      activity of this non-neuronal pathway, suggesting that there is an astrocytic
      basis for epilepsy. Should further experimental analysis corroborate and extend
      this conclusion, this pathway will be a novel target for therapeutic
      intervention.

PMID- 16290020
TI  - 2-Cys peroxiredoxin function in intracellular signal transduction: therapeutic
      implications.
AB  - H(2)O(2) is a reactive oxygen species that has drawn much interest because of its
      role as a second messenger in receptor-mediated signaling. Mammalian 2-Cys
      peroxiredoxins have been shown to eliminate efficiently the H(2)O(2) generated in
      response to receptor stimulation. 2-Cys peroxiredoxins are members of a novel
      peroxidase family that catalyze the H(2)O(2) reduction reaction in the presence
      of thioredoxin, thioredoxin reductase and NADPH. Several lines of evidence
      suggest that 2-Cys peroxiredoxins have dual roles as regulators of the H(2)O(2)
      signal and as defenders of oxidative stress. In particular, 2-Cys peroxiredoxin
      appears to provide selective, specific and localized control of receptor-mediated
      signal transduction. Thus, the therapeutic potential of 2-Cys peroxiredoxins is
      clear for diseases, such as cancer and cardiovascular diseases, that involve
      reactive oxygen species.

PMID- 16290021
TI  - Application of solid-phase microextraction combined with derivatization to the
      enantiomeric determination of amphetamines.
AB  - The utility of combining chiral derivatization and solid-phase microextraction
      (SPME) for the enantiomeric analysis of primary amphetamines by liquid
      chromatography has been investigated. Different derivatization/extraction
      strategies have been evaluated and compared using the chiral reagent o
      phthaldialdehyde (OPA)-N-acetyl-l-cysteine (NAC) and fibres with a Carbowax
      templated resin coating. Amphetamine, norephedrine and 3,4
      methylenedioxyamphetamine (MDA) were used as model compounds. On the basis of the
      results obtained, a new method is presented based on the derivatization of the
      analytes in solution followed by SPME of the OPA-NAC derivatives formed. The
      proposed conditions have been applied to determine the compounds of interest at
      low ppm levels (<or=10 microg/ml) in aqueous and urine samples. Data on the
      linearity, reproducibility, sensitivity and selectivity are given. The utility of
      the described procedure for the quantification of amphetamine, norephedrine and
      MDA enantiomers in different kind of samples is also discussed.

PMID- 16290022
TI  - Primary care physicians' awareness and adherence to cervical cancer screening
      guidelines in Texas.
AB  - BACKGROUND: Cervical cancer screening guidelines were created to help healthcare
      professionals in appropriate screening utilizing the PAP test. However,
      significant variation in cervical cancer screening among primary care physicians
      has been noted. Knowledge of the awareness of and adherence to cervical cancer
      screening guidelines by primary care physicians will help determine how best to
      disseminate and educate these physicians regarding the guidelines in hopes of
      reducing unnecessary screening and improving screening for under screened
      populations. METHODS: A cross-sectional, mailed survey involving Family Medicine
      (FP), Community Internal Medicine (CIM), and Obstetrics/Gynecology (OB)
      physicians practicing in a large University-affiliated, multi-specialty group
      practice associated with an 186,000-member HMO in Central Texas (n = 177) was
      conducted in 2001-2002. RESULTS: Most physicians performed PAP testing (50.4%).
      PAP screening was noted to vary significantly by specialty (P < 0.0001). All OBs
      were aware of at least one published guideline, compared to 96% of FPs and 91% of
      CIMs (P < 0.05). A wide variation was reported regarding adherence to published
      guidelines. In addition, there was significant intraspecialty variation regarding
      adherence to the physicians' own specialty's guidelines. CONCLUSIONS: While most
      physicians in the primary care setting perform PAP tests and are aware of
      published guidelines for PAP screening, adherence to the published guidelines
      varies considerably even in the same clinical setting.

PMID- 16290024
TI  - Writing a publication on cardiac nursing: just do it!

PMID- 16290023
TI  - Smad3 is key to TGF-beta-mediated epithelial-to-mesenchymal transition, fibrosis,
      tumor suppression and metastasis.
AB  - Smads2 and 3 transduce signals of TGF-beta from the cell surface to the nucleus.
      We used mice with a targeted deletion of Smad3 to study the specific
      contributions of this signaling pathway to pathogenic effects of TGF-beta.
      Focusing on models involving epithelial-to-mesenchymal transition (EMT),
      including injury to the lens and retina of the eye and to the kidney, we have
      found that loss of Smad3 blocks EMT and attenuates development of fibrotic
      sequelae. Smad3 also plays a critical role in both the tumor suppressor and pro
      metastatic effects of TGF-beta in carcinogenesis. These observations suggest that
      development of small molecule inhibitors of Smad3 might have clinical application
      in treatment of fibrotic diseases as well as late stage cancers.

PMID- 16290025
TI  - Analysis of Salmonella spp. with resistance to extended-spectrum cephalosporins
      and fluoroquinolones isolated in North America and Latin America: report from the
      SENTRY Antimicrobial Surveillance Program (1997-2004).
AB  - Emerging antimicrobial-resistant Salmonella spp. requires increased efforts to
      appropriately test susceptibility. The SENTRY Antimicrobial Surveillance Program
      monitored Salmonella spp. and detected nalidixic acid-resistant strains with
      elevated fluoroquinolone minimum inhibitory concentration (MIC) results and
      strains with extended-spectrum beta-lactamase (ESBL) "phenotypes" over the last 8
      years. A total of 786 stool and bloodstream isolates from North American and
      Latin American medical centers (2001-2003) were tested by reference broth
      microdilution methods. Genetic analysis was used to further characterize the
      resistance mechanisms. Twenty-one sites forwarded 89 (11.3%) nalidixic acid
      resistant (MIC, > or =32 microg/mL) strains. Nineteen of these isolates were
      studied to determine mutations in the quinolone resistance-determining region
      (QRDR). Among the nalidixic acid-resistant Salmonella spp. isolates,
      fluoroquinolone MIC values were also elevated (8- to 32-fold) compared with "wild
      type" strains. Ciprofloxacin and gatifloxacin (MIC(90), 0.5 microg/mL) were more
      potent than levofloxacin and garenoxacin (1 microg/mL) against nalidixic acid
      resistant strains. Single gyrA mutations were responsible for elevated
      fluoroquinolone MIC values and included D87Y (5), S83F (7), D87N (5), and S83Y
      (2). During 2001, 9 sites contributed 11 (2.9%) strains that met ESBL screening
      criteria (> or =2 microg/mL) for aztreonam or ceftazidime or ceftriaxone. ESBL
      confirmation was evaluated by Etest (AB BIODISK, Solna, Sweden) ESBL strips and
      the enzymes were characterized by polymerase chain reaction and gene sequencing.
      The ESBL phenotype isolates had the following MIC patterns: ceftazidime (> or =16
      microg/mL), aztreonam (4 to >16 microg/mL), and ceftriaxone (8-32 microg/mL). All
      strains were susceptible to cefepime, carbapenems, gentamicin, and
      fluoroquinolones. No strains were inhibited by clavulanic acid consistent with
      all isolates producing the identified CMY-2, AmpC-like enzyme. Fluoroquinolones
      may be compromised among isolates with QRDR mutations detected using nalidixic
      acid as a screening agent. Salmonella spp. with ESBL phenotypes were likely to
      harbor CMY-2 (not an ESBL) and remain susceptible to cefepime, carbapenems, and
      fluoroquinolones, which can be used for serious invasive Salmonella spp.
      infections. Compared with the stool culture isolates, the blood culture isolates
      had higher QRDR mutations, but remained susceptible to the fluoroquinolones. The
      blood culture isolates were more susceptible to penicillins (ampicillin and
      ticarcillin) and not significantly different for ceftriaxone or
      trimethoprim/sulfamethoxazole susceptibility patterns. No QRDR trends over time
      were detected in North America, but increased resistance was observed in Latin
      America.

PMID- 16290026
TI  - Intrathecal synthesis of specific immunoglobulin G antibodies in
      neurocysticercosis: evaluation of antibody concentrations by enzyme-linked
      immunosorbent assay using a whole cysticercal extract and cyst vesicular fluid as
      antigens.
AB  - The demonstration of intrathecal antibody production has proven useful for
      showing the involvement of the central nervous system (CNS) in several diseases.
      In the present study, the intrathecal synthesis of cysticercus-specific
      immunoglobulin G (IgG) antibodies was investigated in 30 patients with
      neurocysticercosis based on calculation of the specific IgG antibody index
      (AI(IgG)). An AI(IgG) > or =1.5 was considered to be indicative of intrathecal
      antibody production. Antibody concentrations in serum and cerebrospinal fluid
      samples were evaluated using an enzyme-linked immunosorbent assay with 2 antigen
      preparations from Taenia solium cysticerci, namely, a whole cysticercal extract
      (TsoW) and the vesicular fluid of the parasite (TsoVF). Intrathecal, cysticercus
      specific IgG antibody synthesis was observed in 21 (70%) and 23 (76.6%) patients
      using the TsoW and TsoVF antigens, respectively. The detection of the intrathecal
      synthesis of specific antibodies may be a potentially useful tool in establishing
      the involvement of CNS in cysticercosis.

PMID- 16290027
TI  - Novel enzyme immunoassay utilizing lipopolysaccharide-binding protein as a
      capture molecule for the measurement of chlamydial lipopolysaccharide in serum.
AB  - Chlamydia pneumoniae causes respiratory tract infections. It has a tendency to
      cause persistent infections, which have been associated with several chronic
      diseases (e.g., atherosclerosis). At present, there is no reliable method for the
      diagnosis of chronic C. pneumoniae infection. We developed a novel enzyme
      immunoassay (EIA) for the quantification of chlamydial lipopolysaccharide (cLPS)
      in human serum. Serum cLPS was solubilized with detergent and then captured by
      LPS-binding protein (LBP). LBP-LPS complexes were bound to the solid phase with
      anti-cLPS monoclonal antibody, and the bound complexes were detected with anti
      LBP antibodies. The new method was used to quantify serum cLPS in acute coronary
      syndrome (ACS) patients (n = 102) and their healthy controls. cLPS was detected
      in 77.5% of ACS patients and in 52% of controls (P < .001) with geometric mean
      concentrations of 1.87 and 0.61 microg/mL (P < .001), respectively. The novel
      cLPS EIA method will provide a potential diagnostic tool for C. pneumoniae
      infection.

PMID- 16290028
TI  - Poliovirus vaccine strains detected in stool specimens of immunodeficient
      children in South Africa.
AB  - After exposure to the oral poliovirus vaccine (OPV), immunocompetent persons
      excrete poliovirus (PV) vaccine strains for a limited period. In contrast,
      immunodeficient individuals remain sometimes chronically infected, and in some
      cases, PV excretion times as long as 10 years have been reported. During
      prolonged replication in the human intestine, the PV vaccine strain almost
      invariably reverts its attenuated character and acquires neurovirulent properties
      (vaccine-derived PVs, or VDPVs), which resemble wild-type PV strains. The aim of
      this study was to determine the occurrence of OPV strains in stools of
      immunodeficient children from a selected area in South Africa, as a first step
      toward future research on the prevalence and potential health impact of VDPVs. In
      a period of 1 year, a total of 164 stool samples of HIV-positive children aged 4
      months to 8 years were studied for the excretion of OPV strains. In addition, 23
      stool samples from healthy immunocompetent children were analyzed after receiving
      their OPV immunization. By applying a reverse transcription-polymerase chain
      reaction in combination with a nested PCR, a total of 54 enteroviruses (EVs) were
      detected in the stool specimens of the immunodeficient children. Using
      restriction enzyme analysis, 13 PVs were distinguished from 41 nonpolio EVs
      (NPEVs). A Sabin-specific RT-triplex PCR confirmed the presence of 7 Sabin PV
      type 1, 4 Sabin PV type 3, and 2 Sabin PV type 2 isolates. The majority of the
      NPEV group was made up of 7 coxsackievirus B3 (CBV3), 6 echovirus 11 (ECV11), 5
      ECV9, and 3 coxsackievirus A6 (CAV6) isolates. According to the results, two of
      the immunodeficient patients (P023 and P140) who had received their last OPV
      immunization more than 15 months before (vaccinated at 14 weeks of age) tested
      positive for Sabin PVs types 3 and 1, respectively. A 5-year-old immunodeficient
      patient (P052) who had received her last OPV immunization more than 42 months
      before (vaccinated at 18 months of age) tested positive for Sabin PV type 1.
      These results suggested that immunodeficient patients vaccinated with OPV might
      excrete potentially pathogenic VDPVs for a prolonged period. These VDPVs may
      circulate in the community, resulting in possible infections in the unvaccinated
      population. Therefore, the information obtained in this study would be essential
      for strategies aimed at the protection of both immunodeficient as well as
      immunocompetent individuals against complications of vaccination with OPV.

PMID- 16290029
TI  - Comparison of polymerase chain reaction with other laboratory methods for the
      diagnosis of American cutaneous leishmaniasis: diagnosis of cutaneous
      leishmaniasis by polymerase chain reaction.
AB  - An evaluation of 5 laboratory methods for diagnosing American cutaneous
      leishmaniasis (ACL) was carried out on patients from an endemic area of Brazil.
      From 164 patients presenting cutaneous lesions, and suspected to have ACL, 133
      (81.1%) were confirmed for the disease by Montenegro skin test (MST) and/or
      parasitologic examination (PE). In both groups of patients, the positivity of
      polymerase chain reaction (PCR) was similar to that of immunofluorescence assay
      and enzyme-linked immunosorbent assay, and higher than that of MST and PE (P <
      .05). In the group of patients suspected to have ACL, PCR presented the same
      positivity as PE and MST together. No correlation between positivity of the
      laboratory methods and clinical or epidemiologic aspects was observed. Our data
      confirmed the value of PCR as an alternative laboratory method for diagnosing
      ACL, especially for those patients with negative PE and MST.

PMID- 16290030
TI  - Epidemiological study of non-polio enterovirus neurological infections in
      children in the region of Monastir, Tunisia.
AB  - The epidemiological, virological, and clinical syndromes of 86 children younger
      than 13 years suspected of having neurological diseases and admitted to Fattouma
      Bourguiba Hospital of Monastir from January 2002 to November 2003 were analyzed.
      The presence of enterovirus was studied in cerebrospinal fluid (CSF) samples by
      reverse transcription-polymerase chain reaction (RT-PCR) and by isolation on cell
      culture. Sixty-one (71%) specimens were positive by RT-PCR, whereas 45 (52.3%)
      were detected by cell culture. Eighty percent (n = 36) of cultured enteroviruses
      were identified, whereas 20% were untyped. Echoviruses were isolated most
      frequently, with 32 cases (71.1%) in children. Echovirus 6 was the most commonly
      identified serotype (22.2%), followed by echovirus 13 (20%). The highest
      incidence on neurological infection (19.6%) occurred in children less than 6
      months of age. The infected children were predominantly male (62.3%).
      Enteroviruses were detected in all the period of the year with the highest rate
      in the spring and summer months. Aseptic meningitis was the most commonly
      diagnosed disease (49%).

PMID- 16290031
TI  - Antimicrobial susceptibility of Haemophilus influenzae isolates collected from 4
      centers in Brazil (1990-2003).
AB  - Antimicrobial susceptibility was determined for 174 Haemophilus influenzae
      strains collected from patients with infection before and after vaccination
      against Hib (1990-1999 and 2000-2003, respectively) from 4 public health 
      laboratories in 3 Brazilian states. All strains were characterized for serotype
      and beta-lactamase production and in vitro activity of the following
      antimicrobial agents: -ampicillin, amoxicillin/clavulanate, ceftriaxone,
      rifampin, chloramphenicol, and trimethoprim/sulfamethoxazole (TMP-SMX). Minimum
      inhibitory concentrations were determined according to the guidelines of the
      National Committee for Clinical Laboratory Standards. Overall, ampicillin
      resistance was observed in 29 strains (17%), all beta-lactamase producers. All
      isolates were susceptible to amoxicillin/clavulanate and ceftriaxone. The
      prevalence of TMP-SMX-resistant isolates increased from 32.6% in the period 1990
      1999 to 65.8% during the period 2000-2003. Among these isolates, 10.0% and 12.5%
      were resistant to ampicillin and chloramphenicol, respectively. Resistance to
      rifampin was detected in 8.2% and 9.7% of the strains, in 2 periods,
      respectively. Continued surveillance is necessary to monitor trends with the H.
      influenzae disease in Brazil.

PMID- 16290032
TI  - On the impossibility of uniform priors on clades.

PMID- 16290034
TI  - Phylogeny of Arthropoda inferred from mitochondrial sequences: strategies for
      limiting the misleading effects of multiple changes in pattern and rates of
      substitution.
AB  - In this study, mitochondrial sequences were used to investigate the relationships
      among the major lineages of Arthropoda. The data matrix used for the analyses
      includes 84 taxa and 3918 nucleotides representing six mitochondrial protein
      coding genes (atp6 and 8, cox1-3, and nad2). The analyses of nucleotide
      composition show that a reverse strand-bias, i.e., characterized by an excess of
      T relative to A nucleotides and of G relative to C nucleotides, was independently
      acquired in six different lineages of Arthropoda: (1) the honeybee mite (Varroa),
      (2) Opisthothelae spiders (Argiope, Habronattus, and Ornithoctonus), (3)
      scorpions (Euscorpius and Mesobuthus), (4) Hutchinsoniella (Cephalocarid), (5)
      Tigriopus (Copepod), and (6) whiteflies (Aleurodicus and Trialeurodes).
      Phylogenetic analyses confirm that these convergences in nucleotide composition
      can be particularly misleading for tree reconstruction, as unrelated taxa with
      reverse strand-bias tend to group together in MP, ML, and Bayesian analyses.
      However, the use of a specific model for minimizing effects of the bias, the
      "Neutral Transition Exclusion" (NTE) model, allows Bayesian analyses to
      rediscover most of the higher taxa of Arthropoda. Furthermore, the analyses of
      branch lengths suggest that three main factors explain accelerated rates of
      substitution: (1) genomic rearrangements, including duplication of the control
      region and gene translocation, (2) parasitic lifestyle, and (3) small body size.
      The comparisons of Bayesian Bootstrap percentages show that the support for many
      nodes increases when taxa with long branches are excluded from the analyses. It
      is therefore recommended to select taxa and genes of the mitochondrial genome for
      inferring phylogenetic relationships among arthropod lineages. The phylogenetic
      analyses support the existence of a major dichotomy within Arthropoda, separating
      Pancrustacea and Paradoxopoda. Basal relationships between Pancrustacean lineages
      are not robust, and the question of Hexapod monophyly or polyphyly cannot be
      answered with the available mitochondrial sequences. Within Paradoxopoda,
      Chelicerata and Myriapoda are each found to be monophyletic, and Endeis
      (Pycnogonida) is, surprisingly, associated with Acari.

PMID- 16290033
TI  - Radiation and diversification within the Ligularia-Cremanthodium-Parasenecio
      complex (Asteraceae) triggered by uplift of the Qinghai-Tibetan Plateau.
AB  - The Ligularia-Cremanthodium-Parasenecio (L-C-P) complex of the Tussilagininae
      (Asteraceae: Senecioneae) contains more than 200 species that are endemic to the
      Qinghai-Tibetan Plateau in eastern Asia. These species are morphologically
      distinct; however, their relationships appear complex. A phylogenetic analysis of
      members of the complex and selected taxa of the tribe Senecioneae was conducted
      using chloroplast (ndhF and trnL-F) and nuclear (ITS) sequences. Phylogenetic
      trees were constructed from individual and combined datasets of the three
      different sequences. All analyses suggested that Doronicum, a genus that has been
      included in the Tussilagininae, should be excluded from this subtribe and placed
      at the base of the tribe Senecioneae. In addition, the Tussilagininae should be
      broadly circumscribed to include the Tephroseridinae. Within the expanded
      Tussilagininae containing all 13 genera occurring in eastern Asia, Tussilago and
      Petasites diverged early as a separate lineage, while the remaining 11 genera
      comprise an expanded L-C-P complex clade. We suggest that the L-C-P clade, which
      is largely unresolved, most likely originated as a consequence of an explosive
      radiation. The few monophyletic subclades identified in the L-C-P clade with
      robust support further suggest that some genera of Tussilagininae from eastern
      Asia require generic re-circumscriptions given the occurrence of subclades
      containing species of the same genus in different parts of the phylogentic tree
      due to homoplasy of important morphological characters used to delimit them.
      Molecular-clock analyses suggest that the explosive radiation of the L-C-P
      complex occurred mostly within the last 20 million years, which falls well within
      the period of recent major uplifts of the Qinghai-Tibetan Plateau between the
      early Miocene to the Pleistocene. It is proposed that significant increases in
      geological and ecological diversity that accompanied such uplifting, most likely
      promoted rapid and continuous allopatric speciation in small and isolated
      populations, and allowed fixation or acquisition of similar morphological
      characters within unrelated lineages. This phenomenon, possibly combined with
      interspecific diploid hybridization because of secondary sympatry during
      relatively stable stages between different uplifts, could be a major cause of
      high species diversity in the Qinghai-Tibetan Plateau and adjacent areas of
      eastern Asia.

PMID- 16290035
TI  - Phylogenetic relationships and divergence time estimate of African anguilliform
      catfish (Siluriformes: Clariidae) inferred from ribosomal gene and spacer
      sequences.
AB  - The catfish family Clariidae comprises species in which the body shape ranges
      from fusiform to anguilliform. Recent studies have shown that this body
      elongation is the result of convergent evolution. This paper aims to study the
      evolution towards anguilliformity in a phylogenetic framework. Sequences of 29
      taxa were analyzed using the neighbor-joining, maximum-likelihood, maximum
      parsimony, and Bayesian inference algorithms and the parsimony algorithm in POY.
      The study yields phylogenetic hypotheses showing well-supported clades.
      Anguilliformity appears to have arisen at least four times, each time having a
      sister group relation with a fusiform Clarias-like ancestor. Divergence time
      estimation indicates that the African Clariidae started radiating between 123 and
      56 My ago.

PMID- 16290036
TI  - Feedback loops link odor and pheromone signaling with reproduction.
AB  - Pheromones can have profound effects on reproductive physiology and behavior in
      mammals. To investigate the neural circuits underlying these effects, we used a
      genetic transneuronal tracer to identify neurons that synapse with GnRH (LHRH)
      neurons, the key regulators of reproduction. We then asked whether the connected
      neurons are presynaptic or postsynaptic to GnRH neurons and analyzed their
      responses to chemosensory cues. Surprisingly, these experiments indicate that
      GnRH neurons receive pheromone signals from both odor and pheromone relays in the
      brain and may also receive common odor signals. Moreover, feedback loops are
      evident whereby GnRH neurons could influence both odor and pheromone processing.
      Remarkably, approximately 800 GnRH neurons communicate with approximately 50,000
      neurons in 53 functionally diverse brain areas, with some connections exhibiting
      sexual dimorphism. These studies reveal a complex interplay between reproduction
      and other functions in which GnRH neurons appear to integrate information from
      multiple sources and modulate a variety of brain functions.

PMID- 16290038
TI  - Colcemid inhibits the rejoining of the nucleotide excision repair of UVC-induced
      DNA damages in Chinese hamster ovary cells.
AB  - In our previous study, we found that colcemid, an inhibitor of mitotic spindle,
      promotes UVC-induced apoptosis in Chinese hamster ovary cells (CHO.K1). In this
      study, a brief treatment of colcemid on cells after but not before UV irradiation
      could synergistically reduce the cell viability. Although colcemid did not affect
      the excision of UV-induced DNA damages such as [6-4] photoproducts or cyclobutane
      pyrimidine dimers, colcemid accumulated the DNA breaks when it was added to cells
      following UV-irradiation. This colcemid effect required nucleotide excision
      repair (NER) since the same accumulation of DNA breaks was barely or not detected
      in two NER defective strains of CHO cells, UV5 or UV24. Furthermore, the colcemid
      effect was not due to semi-conservative DNA replication or mitosis since the
      colcemid-caused accumulation of DNA breaks was also seen in non-replicating
      cells. Moreover, colcemid inhibited rejoining of DNA breaks accumulated by
      hydroxyurea/cytosine arabinoside following UV irradiation. Nevertheless, colcemid
      did not affect the unscheduled DNA synthesis as assayed by the incorporation of
      bromodeoxyuridine. Taken together, our results suggest that colcemid might
      inhibit the step of ligation of NER pathways.

PMID- 16290037
TI  - Olfactory inputs to hypothalamic neurons controlling reproduction and fertility.
AB  - In order to gain insight into sensory processing modulating reproductive
      behavioral and endocrine changes, we have aimed at identifying afferent pathways
      to neurons synthesizing luteinizing hormone-releasing hormone (LHRH, also known
      as gonadotropin-releasing hormone [GnRH]), a key neurohormone of reproduction.
      Injection of conditional pseudorabies virus into the brain of an LHRH::CRE mouse
      line led to the identification of neuronal networks connected to LHRH neurons.
      Remarkably, and in contrast to established notions on the nature of LHRH neuronal
      inputs, our data identify major olfactory projection pathways originating from a
      discrete population of olfactory sensory neurons but fail to document any
      synaptic connectivity with the vomeronasal system. Accordingly, chemosensory
      modulation of LHRH neuronal activity and mating behavior are dramatically
      impaired in absence of olfactory function, while they appear unaffected in mouse
      mutants lacking vomeronasal signaling. Further visualization of afferents to LHRH
      neurons across the brain offers a unique opportunity to uncover complex
      polysynaptic circuits modulating reproduction and fertility.

PMID- 16290039
TI  - Gene function classification using NCI-60 cell line gene expression profiles.
AB  - Gene expression patterns from NCI's panel of 60 cell lines were used to train a
      Neural Network model for classifying genes to pathways. The model assigns
      probabilities to each gene for each of the 21 modeled pathways assigned by the
      Kyoto Encyclopedia of Genes and Genomes. Cross-validation of the model showed
      that 10 of the 21 pathways exhibited good performance in statistical significance
      and accuracy. The model was designed to output gene probabilities that could be
      screened for higher probabilities resulting in higher confidence in
      classification though yielding fewer genes per pathway. The model was deployed on
      5798 genes and our approach allowed us to ascertain the most relevant genes above
      an estimated background. Eight pathways were identified with both good cross
      validation and significant numbers above background, TCA Cycle, Oxidative
      Phosphorylation, Porphyrin Biosynthesis, Ribosome, Polymerases, Proteasome, Cell
      Cycle, and Cell Adhesion. Gene Ontology (GO) annotation was used for additional
      validation of gene classification results. A total of 551 GO annotated genes and
      468 unannotated genes were classified to the 8 pathways. The primary and
      secondary classifications of genes revealed known pathway relationships and
      provide the potential for discovering new pathway relationships.

PMID- 16290040
TI  - Effects of DNA secondary structure on oligonucleotide probe binding efficiency.
AB  - Secondary structure motifs in nucleic acid probes generally impair intended
      hybridization reactions and so efforts to predict and avoid such structures are
      commonly employed in probe design schemes. Another key facet of probe design that
      has received much less attention, however, is that secondary structure at
      targeted probe binding site regions may also impair hybridization. Thus,
      evaluation of both probe and target site secondary structures together should
      improve hybridization prediction and design effectiveness. Several challenges
      confound this goal, including imperfect empirical rules and parameters underlying
      predictions and the fact that folding algorithms scale poorly with respect to
      sequence length. Here, we attempt to quantify the consequences of target site
      structure on predicted hybridization using sequences sampled from the human
      genome. We also provide a methodology for choosing a reasonable "window size"
      around target sites that is as small as possible without compromising folding
      algorithm prediction accuracy.

PMID- 16290042
TI  - What health domains and items are important to patients with knee osteoarthritis?
      A focus group study in a multiethnic urban Asian population.
AB  - OBJECTIVES: To determine important health-related quality of life (HRQoL) domains
      and items within each domain affected by knee osteoarthritis (OA), identify
      ethnic variations in the importance of these domains and items among three ethnic
      groups, and determine how identified domains and items mapped onto selected OA
      specific HRQoL instruments. METHODS: Focus groups were conducted among subjects
      with knee OA stratified by gender, ethnicity, and language spoken. All focus
      groups were audio-taped and transcribed verbatim, with subsequent translation
      into English for groups conducted in other languages. Data analysis was performed
      by combining the key elements of grounded theory and content analysis with the
      assistance of the qualitative software ATLAS/ti 5.0. RESULTS: Five domains (pain,
      physical disability, other symptoms of OA, mental health, and social health) were
      identified from the 74 items reported as important by at least one subject. These
      domains were important for subjects from all ethnic groups with the exception of
      social health, which was more often important for Malay subjects. Items more
      commonly reported as important in the pain, physical disability, and other
      symptoms of OA domains were generally similar across ethnic groups. In contrast,
      important items in the mental and social health domains differed among ethnic
      groups. CONCLUSIONS: The impact of knee OA on HRQoL is broadly similar in both
      Asian and Western socio-cultural contexts. Both similarities and differences in
      important domains and items were identified among subjects with knee OA from
      three major Asian ethnic groups.

PMID- 16290041
TI  - Observing the what and when of language production for different age groups by
      monitoring speakers' eye movements.
AB  - Research on adult age differences in language production has traditionally
      focused on either the production of single words or the properties of language
      samples. Older adults are more prone to word retrieval failures than are younger
      adults (e.g., ). Older adults also tend to produce fewer ideas per utterance and
      fewer left-branching syntactic structures (e.g., ). The use of eye movement
      monitoring in the study of language production allows researchers to examine word
      production processes in the context of multiword utterances, bridging the gap
      between behavior in word production studies and spontaneous speech samples. This
      paper outlines one view of how speakers plan and produce utterances, summarizes
      the literature on age-related changes in production, presents an overview of the
      published research on speakers' gaze during picture description, and recaps a
      study using eye movement monitoring to explore age-related changes in language
      production.

PMID- 16290043
TI  - Intra-articular treatment of hip osteoarthritis: a randomized trial of hyaluronic
      acid, corticosteroid, and isotonic saline.
AB  - OBJECTIVE: Hyaluronic acid (HA) and corticosteroids are both widely used for
      intra-articular treatment of knee osteoarthritis (OA). We examined the effect of
      both drugs in intra-articular treatment for hip OA. METHODS: One hundred and one
      patients with hip OA were included in a prospective double blind study, using a
      randomized controlled trial with a three-armed parallel-group design. Three
      ultrasound-guided, intra-articular injections were given at 14 days interval. The
      primary outcome measure was 'pain on walking', registered on a visual analogue
      scale (VAS). Evaluation was performed at baseline and after 14, 28 and 90 days.
      The study adhered to the Consolidated Standards of Reporting Trials. All analyses
      were based on intention-to-treat analyses, and used 'mixed-procedures' with the
      baseline-observation as covariate. RESULTS: There were no significant
      interactions with respect to Treatment x Time for any of the analyzed outcome
      measures. There was a significant treatment effect for 'pain on walking'
      (P=0.044) due to a significant improvement following corticosteroid compared to
      saline with an effect-size of 0.6 (95% confidence interval: 0.1-1.1, P=0.021). By
      contrast, HA compared to saline had an effect size of 0.4 (-0.1 to 0.9; P=0.13).
      The peak-effect was obtained after 2 weeks. There was no difference between the
      treatment groups at endpoint. No significant side effects of the injections were
      observed. CONCLUSIONS: Patients treated with corticosteroids experienced
      significant improvement during the 3 months of intervention, with an effect size
      indicating a moderate clinical effect. Although a similar significant result
      following treatment with HA could not be shown, the effect size indicated a small
      clinical improvement. A higher number of patients in future HA studies would
      serve to clarify this point.

PMID- 16290044
TI  - Glutaric acid moderately compromises energy metabolism in rat brain.
AB  - Glutaric acidemia type I is an inherited metabolic disorder biochemically
      characterized by tissue accumulation of predominantly glutaric acid (GA).
      Affected patients present frontotemporal hypotrophy, as well as caudate and
      putamen injury following acute encephalopathic crises. Considering that the
      underlying mechanisms of basal ganglia damage in this disorder are poorly known,
      in the present study we tested the effects of glutaric acid (0.2-5mM) on critical
      enzyme activities of energy metabolism, namely the respiratory chain complexes I
      IV, succinate dehydrogenase and creatine kinase in midbrain of developing rats.
      Glutaric acid significantly inhibited creatine kinase activity (up to 26%) even
      at the lowest dose used in the assays (0.2mM). We also observed that CK
      inhibition was prevented by pre-incubation of the homogenates with reduced
      glutathione, suggesting that the inhibitory effect of GA was possibly mediated by
      oxidation of essential thiol groups of the enzyme. In addition, the activities of
      the respiratory chain complex I-III and of succinate dehydrogenase were also
      significantly inhibited by 20 and 30%, respectively, at the highest glutaric acid
      concentration tested (5mM). In contrast, complexes II-III and IV activities of
      the electron transport chain were not affected by the acid. The effect of
      glutaric acid on the rate of oxygen consumption in intact mitochondria from the
      rat cerebrum was also investigated. Glutaric acid (1mM) significantly lowered the
      respiratory control ratio (state III/state IV) up to 40% in the presence of the
      respiratory substrates glutamate/malate or succinate. Moreover, state IV
      respiration linked to NAD and FAD substrates was significantly increased in GA
      treated mitochondria while state III was significantly diminished. The results
      indicate that the major metabolite accumulating in glutaric acidemia type I
      moderately compromises brain energy metabolism in vitro.

PMID- 16290046
TI  - Chronic incidental lead ingestion in a group of captive-reared alligators
      (Alligator mississippiensis): possible contribution to reproductive failure.
AB  - An American alligator (Alligator mississippiensis) breeding facility using male
      and female alligators raised from artificially incubated eggs was established in
      1975. These alligators first reproduced at 6 years of age as compared to 10-12
      years in wild alligators, but the eggs produced showed a lower hatching rate than
      those collected from the wild. By age 21 reproduction had failed almost
      completely. The alligators were sacrificed and tissues collected at necropsy from
      44 captive and 15 wild animals and assayed for metals. Results showed that
      captive alligators had significantly higher tissue levels of lead than wild
      alligators. Cadmium did not differ between wild and captive and selenium was 50%
      higher in wild than captive alligator kidneys. Bone lead in captive alligators
      was 252,443 +/- 20,462 ng/g. High yolk lead was suggested as a probable cause for
      early embryonic death in alligator eggs. The high tissue lead levels in captive
      alligators was attributed to long-term consumption of nutria (Myocastor coypus)
      meat contaminated with lead shot. Liver, ovary, and testis were assayed for lipid
      peroxidation using the thiobarbituric acid (TBA) test. Captive alligators had 3.6
      fold increased TBA-reactive materials in the liver tissue compared to wild. Lipid
      peroxidation was strongly suspected as having been enhanced by consumption of
      rancid nutria meat containing lead.

PMID- 16290045
TI  - Evaluation of the anthelmintic effects of artesunate against experimental
      Schistosoma mansoni infection in mice using different treatment protocols.
AB  - The therapeutic effects of artesunate against experimental Schistosoma mansoni
      infection in mice were analyzed. Previous studies showed that artesunate is
      highly effective against S. japonicum infection, but the action of this drug
      against S. mansoni remained uncovered. The present study examines the optical
      conditions for artesunate against S. mansoni and evaluates the effects of
      inhibiting the sexual maturation of adult worms. Mice infected with S. mansoni
      were orally administered with artesunate according to different schedules. Four
      consecutive administrations of 300 mg/kg of artesunate at 2-week intervals
      conferred almost total protection without the development of pathological lesions
      in the liver. The significant reduction in the number of eggs produced by
      surviving worms and the status of egg maturation suggested that artesunate
      inhibits sexual maturation. Electron microscopy revealed that artesunate caused
      morphological damage, especially on the worm tegument. Artesunate was also very
      effective in iron-deficient mice. Furthermore, the efficacy of artesunate was
      equal to or better than that of artemether against S. japonicum infection.
      Considering that artemether is more toxic, artesunate is currently one of the
      most efficient drugs against immature S. mansoni.

PMID- 16290047
TI  - Extraocular muscle surgery for extorsion after macular translocation surgery new
      surgical technique and clinical management.
AB  - PURPOSE: To report a new extraocular muscle surgery procedure for large-angle
      extorsion, and clinical management of subjective tilt and diplopia after full
      macular translocation (MT360). DESIGN: Consecutive retrospective case series.
      PARTICIPANTS: Seven patients with downward MT360 were evaluated after MT360, both
      before (preoperative) and after (postoperative) extraocular muscle surgery, with
      at least 6 months' follow-up. METHODS: Information gathered included
      demographics, visual acuity, ocular motility, torsion by Maddox rod, ocular
      history, and symptoms of visual disturbance. Surgery on extraocular muscles was
      performed based on the magnitude of torsion measured after MT360 surgery. MAIN
      OUTCOMES MEASURES: Maddox rod testing of torsion after MT360, and both
      preoperative and postoperative extraocular muscle surgery. RESULTS: Mean
      preoperative torsion was reduced from 45.4+/-11.3 degrees to 8.3+/-4.8 degrees
      (at 6 months after MT360) (P = 0.03). Extraocular muscle surgery slightly reduced
      the mean hypertropia of the operated eye (preoperative, 20+/-10 prism diopters
      [PD], vs. postoperative, 11+/-6 PD) (P = 0.06). Mean exotropia was affected
      minimally by extraocular muscle surgery (preoperative, 22+/-31 PD, vs.
      postoperative, 20+/-24 PD). Three patients required a second extraocular muscle
      surgery (performed on the fellow eye) to correct residual extorsion and diplopia.
      Overall, 85% (6/7) of patients were free of both diplopia and tilt after 1 or 2
      extraocular muscle surgeries. CONCLUSIONS: Although our patients continued to
      have significant horizontal/vertical strabismus postoperatively, the extraocular
      muscle surgery performed was successful in reducing the torsional misalignment
      enough such that the remaining diplopia could be successfully ignored or
      suppressed.

PMID- 16290048
TI  - Ocular war injuries of the Iraqi Insurgency,January-September 2004.
AB  - PURPOSE: To document the types and causes of ocular and ocular adnexal injuries
      treated by United States Army ophthalmologists serving in Iraq during the Iraqi
      Insurgency. DESIGN: Prospective hospital-based observational analysis of
      injuries. PARTICIPANTS: All coalition troops, enemy prisoners of war, and
      civilians with severe ocular and ocular adnexal injuries. METHODS: We
      prospectively examined severe ocular and ocular adnexal injuries that were
      treated at the 31st Combat Support Hospital during the portion of the Iraqi
      Insurgency that took place from January 20 through September 12, 2004. MAIN
      OUTCOME MEASURES: Incidences and characteristics of ocular and ocular adnexal
      injuries. RESULTS: During the time observed, 207 patients suffered severe ocular
      or ocular adnexal injuries, including 132 open globes. Blast fragmentation from
      munitions caused 82% of all injuries. The most common single cause of injury was
      the improvised explosive device (IED), which caused 51% of all injuries. Of 41
      eye excisions, 24 were caused by IEDs. CONCLUSIONS: During the portion of the
      Iraqi Insurgency covered in our report, munitions fragments were the most common
      cause of ocular and ocular adnexal injuries. The single most common cause of
      injury was the IED, which produced devastating ocular and ocular adnexal
      injuries. The authors' findings indicate that polycarbonate ballistic eyewear
      could have prevented many, but not all, of the ocular injuries we report.

PMID- 16290049
TI  - Nine-year incidence of age-related macular degeneration in the Barbados Eye
      Studies.
AB  - OBJECTIVE: To provide 9-year incidence estimates of age-related macular
      degeneration (AMD) in a population of African descent. DESIGN: Population-based
      cohort study. PARTICIPANTS: Two thousand seven hundred ninety-three participants
      (81% of eligible) after 9 years' follow-up. MAIN OUTCOME MEASURES: Nine-year
      incidence of AMD-related features, based on fundus photographic gradings and/or
      clinical examinations. RESULTS: The overall incidence rate of early AMD was 12.6%
      (95% confidence interval [CI], 11.0%-14.1%), and that of late AMD was 0.7% (95%
      CI, 0.4%-1.1%). Both increased with age (P<0.05). For early AMD, incidence ranged
      from 10.7% at 40 to 49 years of age to 16.8% at > or =70 years. For late AMD,
      incidence increased from 0.1% to 2.3% in the same age groups. Late AMD was more
      likely to develop in eyes with pigment changes (risk ratio [RR], 5.8; 95% CI, 2.0
      16.8) and retinal pigment epithelial atrophy (RR, 5.4; 95% CI, 1.9-15.8) at
      baseline. Crude RRs indicated significant associations of late AMD to elevated
      systolic blood pressure and diabetes history, but only the diabetes relationship
      was suggested after adjusting for age, with borderline statistical significance
      (age-adjusted RR, 2.7; P = 0.054). CONCLUSIONS: Nine-year data on natural history
      indicate that early AMD is common in this population of African origin, although
      late AMD is infrequent. These long-term observations provide further evidence for
      the lower AMD risk in black populations compared with white populations.

PMID- 16290050
TI  - Ciliary body edema after scleral buckling surgery for rhegmatogenous retinal
      detachment.
AB  - PURPOSE: Choroidal detachment and anterior chamber (AC) shallowing develop in
      some cases after scleral buckling surgery for rhegmatogenous retinal detachment
      (RD). Postoperative angle-closure glaucoma has been reported to occur in 4% of
      cases. It is supposed that compression by the local scleral buckling induces
      ciliary body edema and angle narrowing. This study aimed to evaluate
      quantitatively the time course of changes in ciliary body thickness and AC depth
      (ACD) before and after the scleral buckling procedure using ultrasound
      biomicroscopy. DESIGN: Prospective consecutive case series. PARTICIPANTS: Forty
      six eyes of 44 patients (43.7+/-18.1 years old [mean +/- standard deviation])
      undergoing rhegmatogenous RD surgery. METHODS: Ciliary body thickness and ACD
      were measured before and 3, 7, 14, and 28 days after the procedure. Ultrasound
      biomicroscopy was used to evaluate ACD and ciliary body thickness. MAIN OUTCOME
      MEASURE: Time course of changes in ciliary body thickness and ACD. RESULTS: The
      surgery caused significant increases in ciliary body thickness at 3, 7, and 14
      days postoperatively (P<0.0001, Bonferroni multiple comparison). Ciliary body
      edema reached its peak 3 days after surgery, followed by a gradual decrease
      thereafter. Ciliary body thickness in the encircling group was statistically
      greater than in the segmental buckling group at 3 and 7 days postoperatively
      (P<0.001, Student's t test). The ciliary body was significantly thicker in the
      direction of buckling than on the opposite side 3 days after surgery (P =
      0.0079). In the encircling group, retinal reattachment surgery significantly
      decreased ACD 3 days after surgery (P = 0.018), whereas no significant
      fluctuations were found in the buckling group. CONCLUSIONS: Even without apparent
      choroidal detachment and a shallow AC, subclinical ciliary edema existed in all
      directions of all eyes for at least 1 month after the scleral buckling procedure.
      The ciliary body in the direction of scleral buckling showed greater edema than
      the other areas. Eyes treated with the encircling band showed greater ciliary
      edema than those treated with segmental buckling alone.

PMID- 16290051
TI  - Population requirements for vascular access surgery.
AB  - The native arterio-venous fistula provides the best access for haemodialysis. The
      dialysis population is growing in number, becoming more elderly, and has
      increasingly complex medical co-morbidity. The ability to establish and maintain
      optimal haemodialysis access in this population requires the planning and
      commissioning of operating and diagnostic facilities and the training of
      sufficient suitable surgical specialists. This article outlines the major factors
      that influence the demand for and requirements of a vascular access service for
      the renal failure population.

PMID- 16290052
TI  - Determination of the cut-off value of serum alanine aminotransferase in patients
      undergoing hemodialysis, to identify biochemical activity in patients with
      hepatitis C viremia.
AB  - BACKGROUND: Elevated liver enzymes are infrequent in patients with hepatitis C
      virus (HCV) infection undergoing chronic hemodialysis (HD), suggesting that the
      alanine aminotransferase (ALT) is a poor predictor of hepatocellular damage in
      this population. OBJECTIVE: To establish a more appropriate cut-off value of ALT
      to identify biochemical activity due to HCV infection in HD patients. STUDY
      DESIGN: A total of 217 patients, with an average age of 51.2 years, were
      evaluated between January and October 2002; 130 were males (60%). Serum ALT was
      measured by a kinetic method in five consecutive monthly blood samples, from
      which an average was obtained and divided by the upper limit of normal (ULN). HCV
      antibodies were determined using an enzyme immunoassay, the serum HCV-RNA by
      nested-PCR and HCV genotype by hybridization of the amplified sequence from the
      5'-non-coding region. The cut-off value of ALT was obtained from a ROC curve.
      RESULTS: Within the 217 patients, 18 (8.3%) were anti-HCV-positive, 17 (7.8%) of
      whom were also HCV-RNA-positive. Genotype distribution was: 1a=47%; 1b=18%;
      3a=35%. Mean ALT/ULN (0.77+/-0.57) of the 18 anti-HCV-positive cases was higher
      (p<0.001) than the negative group (0.38+/-0.23). The mean ALT/ULN (0.81+/-0.57)
      of the 17 HCV-RNA-positive cases was also higher (p<0.0001) than the negative
      cases (0.37+/-0.23). The cut-off value of ALT to distinguish the anti-HCV
      positive from negative patients was 0.50% or 50% of the ULN (sensitivity=67%;
      specificity=83%). According to the HCV-RNA, the cut-off value of ALT was 0.45% or
      45% of the ULN (sensitivity=71%; specificity=80%). CONCLUSION: Reducing the cut
      off of ALT by half, enables a better identification of biochemical activity in
      patients with HCV infection on chronic HD.

PMID- 16290053
TI  - Enhanced acetylcholine-induced dilation in afferent arterioles in simvastatin-fed
      rats.
AB  - OBJECTIVE: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors
      have been shown to increase renal blood flow and glomerular filtration rate
      independent of their lipid lowering effects. The purpose of this study was to
      determine the effect of simvastatin on acetylcholine-induced vasodilation in the
      renal microcirculation. The hypothesis of the study was that simvastatin would
      increase acetylcholine-induced vasodilation in the renal microcirculation.
      METHODS: The hydronephrotic kidney preparation was used. On the day of the
      experiment the kidney was prepared for videomicroscopy and dose-response curves
      were done with acetylcholine and sodium nitroprusside (10(-10) M to 10(-5) M) in
      simvastatin-fed rats ??(n=8) and control rats (n=13). The vasodilator responses
      of afferent and efferent arterioles were directly quantitated using
      videomicroscopy. L-NAME; (N(omega)-nitro-L-arginine methyl ester) was also given
      in a group of simvastatin-fed rats (10(-5) M) to determine if it would block the
      acetylcholine (Ach)-induced vasodilation. RESULTS: Simvastatin enhanced Ach
      induced vasodilation in the afferent arteriole compared to control rat responses
      to Ach. At 10(-7) M, ACH caused a 31.6+/-7.2% increase from baseline diameter in
      the afferent arteriole in the simvastatin-fed rats compared to a 23+/-8.1%
      vasodilation in the control rats (p<0.05). There were no differences in the
      response to ACH in the efferent arteriole between the two groups. L-NAME
      completely abolished the ACH response in the simvastatin-fed rats. CONCLUSIONS:
      The increase in renal blood flow and glomerular filtration rate observed with
      simvastatin may be due to its preglomerular vasodilator effects. This may be due
      to an increase in nitric oxide production.

PMID- 16290054
TI  - Endothelin-1 activation of JAK2 in vascular smooth muscle cells involves NAD(P)H
      oxidase-derived reactive oxygen species.
AB  - Endothelin-1 (ET-1) and JAK2 are both implicated in diabetic complications.
      Therefore, we investigated whether ET-1 differentially activates JAK2 under
      conditions of normal (5 mM) and high (25 mM) glucose. We tested the hypothesis
      that reactive oxygen species mediate the activation of JAK2 in response to ET-1.
      In rat aortic vascular smooth muscle cells (VSMC), ET-1 (10 (- 7) M, 5 min)
      stimulated the activation of JAK2, which was further enhanced under high glucose
      conditions. Allopurinol (xanthine oxidase inhibitor, 1 microM) and l-NAME (nitric
      oxide synthase inhibitor, 1 mM) had no effect on ET-1-induced JAK2 activation,
      while apocynin (NAD(P)H oxidase inhibitor 100 microM) resulted in a significant
      inhibition of ET-1-induced JAK2 and MAPK activation. Overexpression of SOD did
      not inhibit ET-1-induced activation of JAK2, but catalase (50 units/mL) treatment
      resulted in complete inhibition. In vivo administration of apocynin (1.5 mM)
      resulted in a significant decrease ( 50%), while the ETA receptor antagonist ABT
      627 completely inhibited phosphorylation of JAK2 in aortae from STZ-induced
      diabetic rats. Additionally, DHE staining of aortic sections was significantly
      reduced in diabetic rats treated with ABT-627. These data suggest that in VSMC,
      ET-1 via the ETA receptor, utilizes NAD(P)H oxidase to activate JAK2.

PMID- 16290055
TI  - Preoperative computed tomography and selection of patients with colorectal
      peritoneal carcinomatosis for cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy.
AB  - AIM: A survival benefit has been observed for colorectal cancer patients with
      peritoneal carcinomatosis treated by cytoreductive surgery with intraoperative
      hyperthermic intraperitoneal chemotherapy (HIPEC). However, this treatment
      modality is associated with a considerable morbidity and mortality and in a
      significant number of patients survival is not improved. We studied whether poor
      survivors could be identified on preoperative computed tomography (CT), in order
      to avoid unnecessary surgery. PATIENTS AND METHODS: Films of abdominopelvic CT
      scans from 25 such patients treated by cytoreductive surgery and HIPEC were
      retrospectively analysed by two radiologists separately. A simplified peritoneal
      cancer index (SPCI) was used to determine the extent of peritoneal involvement.
      Correlation between the on preoperative CT based SPCI-scores as well as number of
      involved abdominopelvic areas (N) and survival was examined with the log-rank
      test. The relation between each affected region and survival was evaluated with
      Cox regression analysis. RESULTS: The preoperative SPCI- and N-scores of one of
      the radiologists had no statistically significant prognostic value, while for the
      second radiologist SPCI > or = 7 and N > or = 4 were associated with particularly
      poor outcome. Additionally, the presence of ileocaecal region involvement and,
      depending on the radiologist, the occurrence of tumour deposits in the left
      subdiaphragmatic area on CT appeared to be unfavourable prognostic signs.
      CONCLUSIONS: The prognostic value of preoperative conventional CT appeared to be
      radiologist dependent and may, therefore, be of limited value in selecting
      colorectal cancer patients with peritoneal carcinomatosis who will not benefit
      from extensive cytoreductive surgery followed by HIPEC.

PMID- 16290056
TI  - Performances of a new prototype handheld scintillating probe for the search of
      sentinel lymph nodes in breast cancer.
AB  - AIM: The aim of this study is to evaluate the performances of a new prototype
      handheld gamma probe in a series of patients with infiltrative breast cancer
      justifying sentinel lymph node (SLN) excision. METHODS AND PATIENTS: SLN excision
      was performed on nine patients being treated for infiltrative breast cancer.
      After preoperative radio-isotope injection and lymphoscintigraphy, individual
      removal of all radioactive nodes was performed after their localisation using a
      novel new prototype handheld gamma intraoperative probe named CarolIReS. The
      activity of SLN following resection has been measured by a gamma ray counter. The
      mean geometrical detection efficiency of this gamma ray counter has been obtained
      by Monte Carlo simulation. RESULTS: With respect to the total number of SLNs
      identified by the CarolIReS probe, the detection probability was 80% for the
      lymphoscintigraphy. A mean number of 2.2 (1-5) SLNs per patient was detected
      after the complete SLN procedure. Among the removed SLNs, 19 were axillary SLN,
      17 were located in the level I of Berg, two were located in the Rotter area and
      one was an intramammary SLN (ISLN) located in the lower inner area of the breast.
      The detection efficiency of the CarolIReS probe ranged from 2.1 to 100.0cpskBq(
      1) referred to the activity of the SLN at the time of the surgery. CONCLUSION:
      This study shows that the CarolIReS probe is well adapted to the SLN detection
      and allows an efficient identification of both axillary and intramammary lymph
      nodes.

PMID- 16290057
TI  - Expression of TAp73 and DeltaNp73 isoform transcripts in thyroid tumours.
AB  - AIM: This study was aimed to determine p73 status in thyroid tumours. METHODS:
      Differential expression of the TAp73, DeltaTAp73 transcripts was measured in a
      panel of 60 thyroid malignancies by quantitative RT-PCR. RESULTS: By comparison
      to normal thyroid tissue surrounding the tumours, we observed significant
      downregulation of TP73 transcripts in adenomas and in differentiated carcinomas.
      Correlations were found in normal tissue specimens between the expression of
      TAp73 and DeltaNp73 transcripts and that of p53, p14ARF p16INK4a, but these
      correlations were lost in carcinomas (PTC or FTC). CONCLUSIONS: We have found
      significant variations of TAp73, DeltaNp73, p53, p14ARF p16INK4a, expressions and
      correlations between the expressions of those different genes in thyroid cancer.

PMID- 16290058
TI  - Synthesis, characterization and DNA-binding properties of rac-[Ru(5,6
      dmp)2(dppz)]2+--enantiopreferential DNA binding and co-ligand promoted exciton
      coupling.
AB  - The new mixed ligand complex [Ru(5,6-dmp)2(dppz)]Cl2 [5,6-dmp = 5,6-dimethyl-1,10
      phenanthroline, dppz = dipyrido[3,2-a:2',3'-c]phenazine] has been isolated and
      its DNA-binding properties studied by employing UV-visible (UV-Vis), steady-state
      and time-resolved emission and circular dichroism spectral methods, viscometry,
      thermal denaturation and cyclic/differential pulse voltammetric techniques. The
      complex acts as a 'molecular light-switch' on binding to DNA, but the enhancement
      in emission intensity is only 75% of that of the parent complex
      [Ru(phen)2(dppz)]2+ (phen = 1,10-phenanthroline). The emission decay curves and
      quenching studies suggest two different DNA-binding modes both involving
      intercalation of the dppz ligand of [Ru(5,6-dmp)2(dppz)]Cl2. The characteristic
      red-shift of the induced CD signal, which is not observed for the phen analogue,
      arises from exciton coupling. The hydrophobicity and polarizability of 5,6-dmp co
      ligand strongly favour the formation of a stable structural and electronic
      scaffold on the DNA surface for the unbound molecules to couple with the DNA
      bound complexes facilitating spontaneous assembly of novel extended molecular
      aggregates using DNA as a helical nanotemplate. This observation is consistent
      with the shift in Ru(II)/Ru(III) redox potential to more positive values with a
      dramatic drop in peak current on binding of the 5,6-dmp complex to calf thymus
      (CT) DNA. Equilibrium dialysis experiments monitored by CD spectroscopy
      unambiguously reveal the preferential binding of the delta-enantiomer to the
      right-handed calf thymus (CT) DNA. The 5,6-dmp complex exhibits preferential
      binding to [d(AT)6]2 over [d(GC)6]2 and the complex aggregates formed consist of
      six [Ru(5,6-dmp)2(dppz)]2+ cations per base pair of [d(AT)6]2; however, only one
      [Ru(phen)2(dppz)]2+ cation per base pair is involved in DNA binding.

PMID- 16290059
TI  - Biochemical and spectroscopic characterization of an aldehyde oxidoreductase
      isolated from Desulfovibrio aminophilus.
AB  - Aldehyde oxidoreductase (AOR) activity has been found in a number of sulfate
      reducing bacteria. The enzyme that is responsible for the conversion of aldehydes
      to carboxylic acids is a mononuclear molybdenum enzyme belonging to the xanthine
      oxidase family. We report here the purification and characterization of AOR
      isolated from the sulfate-reducing bacterium Desulfovibrio (D.) aminophilus DSM
      12254, an aminolytic strain performing thiosulfate dismutation. The enzyme is a
      homodimer (ca. 200 kDa), containing a molybdenum centre and two [2Fe-2S] clusters
      per monomer. UV/Visible and electron paramagnetic resonance (EPR) spectra of D.
      aminophilus AOR recorded in as-prepared and reduced states are similar to those
      obtained in AORs from Desulfovibrio gigas, Desulfovibrio desulfuricans and
      Desulfovibrio alaskensis. Despite AOR from D. aminophilus is closely related to
      other AORs, it presents lower activity towards aldehydes and no activity towards
      N-heterocyclic compounds, which suggests another possible role for this enzyme in
      vivo. A comparison of the molecular and EPR properties of AORs from different
      Desulfovibrio species is also included.

PMID- 16290060
TI  - 8-Nitroguanine formation in oral leukoplakia, a premalignant lesion.
AB  - Oral leukoplakia is a premalignant lesion associated with development of oral
      cancer. To clarify the mechanism of development of oral carcinogenesis from
      leukoplakia, we examined DNA damage in oral epithelium of biopsy specimens of
      patients with leukoplakia by immunohistochemical methods. Histological changes,
      such as epithelial dysplasia and infiltration of inflammatory cells were observed
      in oral tissues of leukoplakia patients. A double immunofluorescence labeling
      study demonstrated that the accumulation of mutagenic 8-nitroguanine, an
      indicator of nitrative DNA damage, and 8-oxo-7,8-dihydro-2'-deoxyguanosine, an
      indicator of oxidative DNA damage, was apparently observed in the oral epithelium
      of patients with leukoplakia, whereas little or no immunoreactivity was observed
      in normal oral mucosa. Expression of inducible nitric oxide synthase (iNOS) was
      also observed in oral epithelium of leukoplakia patients. Immunoreactivity of 3
      nitrotyrosine, an indicator of nitrative stress, was observed in oral epithelial
      cells and colocalized with 8-nitroguanine. Moreover, proliferating cell nuclear
      antigen and p53 were expressed in 8-nitroguanine-positive epithelial cells in the
      basal layer. These results suggest that iNOS-mediated nitrative stress
      contributes to development of oral carcinogenesis from leukoplakia through DNA
      damage as well as oxidative stress.

PMID- 16290061
TI  - TRPC6 - a new podocyte gene involved in focal segmental glomerulosclerosis.
AB  - Hereditary kidney diseases have long been an enigma with respect to the identity
      of the mutated genes and the mechanisms by which they develop. Recently, the
      podocyte has been identified as a primary target in both genetic and acquired
      glomerular disorders. Mutations discovered by Winn et al. and Reiser et al. in
      the gene encoding TRPC6, a non-selective cation channel of the TRP family
      expressed in podocyte foot processes, have been shown to cause focal segmental
      glomerulosclerosis. It remains to be determined whether these mutations lead to
      (i) impaired channel function that initiates a new pathogenic mechanism or (ii)
      decreased ability of the podocyte to adapt to normal physiological challenges
      that account for disease development, as suggested for other late-onset autosomal
      dominant podocyte disorders.

PMID- 16290062
TI  - Molecular epidemiology of clonal diploids: a quick overview and a short DIY (do
      it yourself) notice.
AB  - In this short review we report the basic notions needed for understanding the
      population genetics of clonal diploids. We focus on the consequences of clonality
      on the distribution of genetic diversity within individuals, between individuals
      and between populations. We then summarise how to detect clonality in mainly
      sexual populations, conversely, how to detect sexuality in mainly clonal
      populations and also how genetic differentiation between populations is affected
      by clonality in diploids. This information is then used for building recipes on
      how to analyse and interpret genetic polymorphism data in molecular epidemiology
      studies of clonal diploids.

PMID- 16290063
TI  - A comprehensive review of the Paced Auditory Serial Addition Test (PASAT).
AB  - The Paced Auditory Serial Addition Test (PASAT) was developed to assess the
      effects of traumatic brain injury (TBI) on cognitive functioning. Subsequent
      research has shown that the PASAT has clinical utility in detecting impairments
      in cognitive processing in patients with a wide variety of neuropsychological
      syndromes. Gronwall and Sampson (1974) originally assumed the PASAT measured
      speed of information processing. However, the PASAT is now recognized as a
      measure of multiple functional domains because it requires the successful
      completion of a variety of cognitive functions, primarily those related to
      attention. While the PASAT has demonstrated good psychometric properties such as
      high levels of internal consistency and test-retest reliability, several issues
      should be considered when administering and interpreting this test. For example,
      test-retest scores show that the PASAT is extremely susceptible to practice
      effects. The PASAT is also negatively affected by increasing age, decreasing IQ,
      and low math ability. Administration of the PASAT creates an undue amount of
      anxiety and frustration in participants which affects their performance on this
      and other neuropsychological tests, and may subsequently increase their
      reluctance to return for follow up testing. Demands for rapid responding place
      individuals with speech or language impairment at a distinct disadvantage, as it
      does for those who naturally speak slowly for cultural or geographic reasons. In
      conclusion, the PASAT represents a reliable test that has legitimate but
      restricted clinical applications. A low score on the PASAT may not necessarily
      indicate or confirm the presence of neurological pathology. The PASAT is a highly
      sensitive, non-specific test and as such, care must be taken to identify the
      reasons underlying any low score before interpreting it as clinically
      significant.

PMID- 16290064
TI  - The eukaryotic Pso2p/Snm1p family revisited: in silico analyses of Pso2p A, B and
      Plasmodium groups.
AB  - The eukaryotic family of Pso2/Snm1 exo/endonuclease proteins has important
      functions in repair of DNA damages induced by chemical interstrand cross-linking
      agents and ionizing radiation. These exo/endonucleases are also necessary for
      V(D)J recombination and genomic caretaking. However, despite the growing
      biochemical data about this family, little is known about the number of
      orthologous/paralogous Pso2p/Snm1p sequences in eukaryotes and how they are
      phylogenetically organized. In this work we have characterized new Pso2p/Snm1p
      sequences from the finished and unfinished eukaryotic genomes and performed an in
      depth phylogenetic analysis. The results indicate that four phylogenetically
      related groups compose the Pso2p/Snm1p family: (i) the Artemis/Artemis-like
      group, (ii) the Pso2p A group, (iii) the Pso2p B group and (iv) the Pso2p
      Plasmodium group. Using the available biochemical and genomic information about
      Pso2p/Snm1p family, we concentrate our research in the study of Pso2p A, B and
      Plasmodium groups. The phylogenetic results showed that A and B groups can be
      organized in specific subgroups with different functions in DNA metabolism.
      Moreover, we subjected selected Pso2p A, B and Plasmodium proteins to hydrophobic
      cluster analysis (HCA) in order to map and to compare conserved regions within
      these sequences. Four conserved regions could be detected by HCA, which are
      distributed along the metallo-beta-lactamase and beta-CASP motifs. Interestingly,
      both Pso2p A and B proteins are structurally similar, while Pso2p Plasmodium
      proteins have a unique domain organization. The possible functions of A, B and
      Plasmodium groups are discussed.

PMID- 16290065
TI  - CNS malformations: gene locations of known human mutations.

PMID- 16290066
TI  - Dynamic changes in circulating leukocytes during the induction of equine
      laminitis with black walnut extract.
AB  - Administration of black walnut heartwood extract (BWHE) via nasogastric tube
      induces acute laminitis in horses. However, the processes responsible for the
      development of laminitis, including laminitis induced with BWHE, remain unclear.
      The results of recent studies indicate that administration of BWHE initiates an
      inflammatory response in the laminar tissues and that this response may be due to
      extravasation of activated leukocytes from the circulation. This study examines
      the effects of BWHE administration on the dynamics of circulating neutrophils and
      monocytes, and the capacity of blood leukocytes to produce radical oxygen species
      (ROS) over the time period from administration of BWHE to the development of
      lameness consistent with Obel grade I laminitis. Individual horses, free of pre
      existing musculoskeletal disease, were administered either 6l of BWHE or an equal
      volume of water at time 0 (T=0). Blood samples were collected prior to dosing and
      at 1, 2, 3, 4, 6, 8, 10 and 12h after dosing, or until the onset of Obel grade I
      laminitis. For each sample, total leukocyte counts were determined followed by
      collection of buffy coats and removal of erythrocytes by hypotonic lysis.
      Leukocytes were either fixed for flow cytometric assessment of differential
      counts or maintained in culture to measure endogenous and phorbol ester-induced
      production of ROS. At each sample time, the number of cells recovered and the
      flow cytometric differential counts were compared with corresponding total
      leukocyte counts determined by the Clinical Pathology laboratory. Horses
      administered BWHE had a significant reduction in circulating leukocytes at 3-4 h
      relative to values for horses administered the same volume of water. Horses that
      developed Obel grade I laminitis had a significant reduction in circulating
      leukocytes when compared to values for horses administered BWHE that did not
      become lame. Flow cytometric analysis revealed a consistent decrease in the total
      number of monocytes obtained from horses that developed laminitis. In these same
      horses, the endogenous level of ROS production was significantly higher at T=0
      than for horses that did not become lame. Furthermore, production of ROS by
      leukocytes from horses that developed laminitis increased significantly and
      coincided with the decrease in circulating leukocytes. Collectively, these
      findings support a role for systemic activation of leukocytes and induction of
      inflammation by BWHE as a factor in the early pathogenesis of acute laminitis.
      Because laminitis often develops as a sequel to diseases characterized by
      systemic inflammatory events, activation and emigration of neutrophils and
      monocytes may be important factors in the early pathogenesis of laminitis in
      clinical cases.

PMID- 16290067
TI  - Database of mouse strains carrying targeted mutations in genes affecting
      biological responses to DNA damage Version 7.
AB  - We present Version 7 of a database of mouse mutant strains that affect biological
      responses to DNA damage. This database is also electronically available at
      http://pathcuricl.swmed.edu/research/research.htm.

PMID- 16290069
TI  - Magnetization and spin-spin energy diffusion in the XY model: a diagrammatic
      approach.
AB  - It is shown that the diagrammatic cluster expansion technique for equilibrium
      averages of spin operators may be straightforwardly extended to the calculation
      of time-dependent correlation functions of spin operators. We use this technique
      to calculate exactly the first two non-vanishing moments of the spin-spin and
      energy-energy correlation functions of the XY model with arbitrary couplings, in
      the long-wavelength, infinite temperature limit appropriate for spin diffusion.
      These moments are then used to estimate the magnetization and spin-spin energy
      diffusion coefficients of the model using a phenomenological theory of Redfield.
      Qualitative agreement is obtained with recent experiments measuring diffusion of
      dipolar energy in calcium fluoride.

PMID- 16290068
TI  - The plant alkaloid Sanguinarine affects swine granulosa cell activity.
AB  - Sanguinarine (SA) has been used in toothpastes and oral rinse products and has
      been recently applied to livestock nutrition. This study was undertaken to
      examine the reproductive-related consequences of this feeding supplementation,
      evaluating SA effects (10, 100 and 300 nM) on swine granulosa cell
      steroidogenesis, oxidative enzyme activities (peroxidase, catalase and superoxide
      dismutase), and proliferation. Since angiogenesis is fundamental for follicle
      development, we also tested the impact of SA exposure on vascular endothelial
      growth factor (VEGF) production. SA had no effect on proliferation and did not
      alter progesterone production, although it significantly reduced estradiol
      synthesis at the two highest concentrations tested (100 and 300 nM). SA addition
      to granulosa cell culture inhibited VEGF production and increased peroxidase and
      catalase activities at all tested concentrations while superoxide dismutase
      activity was increased only at 300 nM. Our data suggest that SA can negatively
      affect some key biochemical parameters of ovarian granulosa cells.

PMID- 16290070
TI  - A peptide DNA surrogate that binds and inhibits anti-dsDNA antibodies.
AB  - Autoantibodies to dsDNA are an important diagnostic marker and pathogenic factor
      for systemic lupus erythematosus (SLE). Although the anti-dsDNA antibodies
      present in SLE are indicative of an antigen-driven response, the antigen has not
      been conclusively identified. The specific SLE anti-dsDNA antibodies were
      obtained by affinity purification using a dsDNA-coupled Sepharose column. Using
      the anti-dsDNA antibodies to screen a phage peptide display library, we
      demonstrated that purified polyclonal anti-dsDNA antibodies and a monoclonal anti
      dsDNA antibody specifically bind a 15 mer peptide ASPVTARVLWKASHV. This
      chemically synthesized peptide could be recognized by anti-dsDNA antibodies in
      ELISA and Dot blot. This 15 mer peptide can inhibit anti-dsDNA antibodies binding
      to dsDNA antigen in immunoassays and in the Crithidia luciliae assay while a
      control peptide did not inhibit anti-dsDNA antibodies. This study demonstrates
      the potential usefulness of the peptide DNA surrogate in diagnostic tests of SLE
      and in the investigation of the origin of anti-dsDNA antibodies. It may also be
      used in studies of the DNA-anti-DNA antibody interaction.

PMID- 16290071
TI  - Apoptosis of CD57+ and CD57- lymphocytes in the lung and blood of HIV-infected
      subjects.
AB  - Patients infected with HIV frequently have a CD8+ lymphocytic alveolitis
      consisting of HIV-specific CD8+CD57- cytotoxic T lymphocytes. However, in late
      stage disease, there is expansion of a CD8+CD57+ population with suppressive
      properties. We examined role of lymphocyte apoptosis in the expansion of the
      CD8+CD57+ lymphocytes in late stage HIV in the lung and blood compartment in
      human subjects. Fas was expressed on virtually all lung lymphocytes from HIV
      infected and normal subjects. Fas ligand expression was increased in HIV
      infection in both CD8+CD57+ and CD8+CD57- lymphocytes, though a significantly
      greater percentage of CD8+CD57+ cells expressed this marker. CD8+CD57+
      lymphocytes in normal and HIV-infected subjects underwent more apoptosis than
      CD8+CD57- cells. However, in late stage HIV infection, the percentage of
      CD8+CD57+ cells undergoing apoptosis declined. These data demonstrate that under
      normal conditions CD8+CD57+ cells appear destined to undergo programmed cell
      death. Expansion of suppressive CD8+CD57+ cells in the lungs of HIV-infected
      subjects with advanced disease may be due to the failure of this normal
      regulatory process.

PMID- 16290072
TI  - Apoptosis of T cells in peripheral blood and cerebrospinal fluid is associated
      with disease activity of multiple sclerosis.
AB  - Apoptotic elimination of pathogenic T cells is considered to be one of regulatory
      mechanisms in multiple sclerosis (MS). To explore the potential relationship
      between Fas-mediated apoptosis and the disease course of MS, we examined
      apoptosis, defined by annexin V (AV) binding, and Fas (CD95) expression in CD4+
      and in CD8+ T cells in MS patients by using five-color flow cytometry. The
      percentage of AV+CD4+CD3+ cells and CD95+AV+CD4+CD3+ cells in peripheral blood
      and cerebrospinal fluid (CSF) were significantly decreased in active MS patients
      compared with inactive MS patients. A significantly lower proportion of
      CD95+AV+CD8+CD3+ cells in CSF was observed in active MS patients compared with
      inactive MS patients, but not in peripheral blood. These results indicate that
      the resistance of T cells to Fas-mediated apoptosis is involved in exacerbation
      of MS and/or that Fas-mediated apoptosis of T cells is associated with remission
      of MS.

PMID- 16290073
TI  - A sensitive and selective HPLC/ESI-MS/MS assay for the simultaneous
      quantification of 16-dehydropregnenolone and its major metabolites in rabbit
      plasma.
AB  - A sensitive, selective and rapid liquid chromatographic/electrospray ionization
      tandem mass spectrometric assay was developed and validated for the simultaneous
      quantification of 16-dehydropregnenolone (DHP) and its five metabolites 4,16
      pregnadien-3, 20-dione (M(1)), 5-pregnene-3beta-ol-20-one (M(2)), 5-pregnene
      3beta, 20-diol (M(3)), 5-pregnene-3beta-ol-16, 17-epoxi-20-one (M(4)) and 5,16
      pregnadien-3beta, 11-diol-20-one (M(5)) in rabbit plasma using dexamethasone as
      internal standard (IS). The analytes were chromatographed on Spheri-5 RP-18
      column (5 microm, 100 mm x 4.6 mm i.d.) coupled with guard column using
      acetonitrile:ammonium acetate buffer (90:10, v/v) as mobile phase at a flow rate
      of 0.65 ml/min. The quantitation of the analytes was carried out using API 4000
      LC-MS-MS system in the multiple reaction monitoring (MRM) mode. The method was
      validated in terms of linearity, specificity, sensitivity, recovery, accuracy,
      precision (intra- and inter-assay variation), freeze-thaw, long-term, auto
      injector and dry residue stability. Linearity in plasma was observed over a
      concentration range of 1.56-400 ng/ml with a limit of detection (LOD) of 0.78
      ng/ml for all analytes except M(3) and M(5) where linearity was over the 3.13-400
      ng/ml with LOD of 1.56 ng/ml. The absolute recoveries from plasma were consistent
      and reproducible over the linearity range for all analytes. The intra- and inter
      day accuracy and precision method were within the acceptable limits and the
      analytes were stable after three freeze-thaw cycles and their dry residues were
      stable at -60 degrees C for 15 days. The method was successfully applied to
      determine concentrations of DHP and its putative metabolites in plasma during a
      pilot pharmacokinetic study in rabbits.

PMID- 16290074
TI  - Stereoselective HPLC assay of donepezil enantiomers with UV detection and its
      application to pharmacokinetics in rats.
AB  - This investigation describes a new precise, sensitive and accurate
      stereoselective HPLC method for the simultaneous determination of donepezil
      enantiomers in tablets and plasma with enough sensitivity to follow its
      pharmacokinetics in rats up to 12h after single oral dosing. Enantiomeric
      resolution was achieved on a cellulose tris (3,5-dimethylphenyl carbamate) column
      known as Chiralcel OD, with UV detection at 268 nm, and the mobile phase
      consisted of n-hexane, isopropanol and triethylamine (87:12.9:0.1). Using the
      chromatographic conditions described, donepezil enantiomers were well resolved
      with mean retention times of 12.8 and 16.3 min, respectively. Linear response (r
      > 0.994) was observed over the range of 0.05-2 microg/ml of donepezil
      enantiomers, with detection limit of 20 ng/ml. The mean relative standard
      deviation (R.S.D.%) of the results of within-day precision and accuracy of the
      drug were < or =10%. There was no significant difference (p > 0.05) between inter
      and intra-day studies for each enantiomers which confirmed the reproducibility
      of the assay method. The mean extraction efficiency was 92.6-93.2% of the
      enantiomers. The proposed method was found to be suitable and accurate for the
      quantitative determination of donepezil enantiomers in tablets. The assay method
      also shows good specificity to donepezil enantiomers, and it could be
      successfully applied to its pharmacokinetic studies and to therapeutic drug
      monitoring.

PMID- 16290075
TI  - Optimisation of an extraction method for the determination of prostaglandin E2 in
      plasma using experimental design and liquid chromatography tandem mass
      spectrometry.
AB  - A new extraction method has been developed for the extraction of prostaglandin
      E(2) (PGE(2)) from human plasma of patients suffering chronic inflammatory
      disorders. The extraction solvents were optimised systematically and
      simultaneously by using a central composite design. The optimised method involves
      precipitation of the protein fraction, centrifugation, evaporation and
      dissolution of the supernatant in the mobile phase, screening to confirm the
      presence of the analyte, and quantification of the positive samples by liquid
      chromatography tandem ion-trap mass spectrometry. Tandem mass spectrometry in
      negative mode was performed by isolating and fragmenting the ion [PGE(2)-H](-)
      signal m/z 351. Identification and quantification was carried out by extracting
      the ion fragment chromatograms at 333, 315 and 271 m/z. The quantitative
      determination was linear for the low nanogram (1-50 ng/ml) and upper picogram
      (400-1000 pg/ml) range studied, using 15 and 0.5 ng/ml of internal standard,
      respectively. The lower limit of detection was 2.5 pg for an injection volume of
      25 microl. The optimised extraction method showed high reproducibility
      (coefficients of variation<4%) and recovery values, estimated from standard
      addition experiments, ranging from 96 to 98%.

PMID- 16290076
TI  - The postnatal ontogeny of gonadotroph cells in the female sheep. Developmental
      patterns of synthesis, storage and release of gonadotrophic hormones.
AB  - The aim of this study was to determine the developmental changes in the
      synthesis, storage and release of luteinizing hormone (LH) and follicle
      stimulating hormone (FSH) in the hypophyseal gonadotroph cells from infancy to
      peripuberty of ovine ontogeny. An examination has been made in 15 infantile (12-,
      15-week-old) and juvenile (22-, 30-week-old) ovary-intact sheep.
      Histomorphological and functional changes in the adenohypophyseal population of
      gonadotrophs were assayed with hybridohistochemistry, immunohistochemistry and
      radioimmunoassay. The percentage of the adenohypophyseal area (PAA) occupied by
      gonadotrophs containing LHbeta-mRNA or FSHbeta-mRNA was highest (P < 0.05) in the
      15-week-old sheep compared with the other stages. The gradual increase in the PAA
      occupied by immunoreactive (ir)-LHbeta-cells from the 12th to 30th week of age
      was observed (P < 0.05) and has been interpreted as the increase in the storage
      of LH. This histomorphological change was accompanied by the gradual increase in
      the LH pulse frequency from the 15th to 30th week of age (P < 0.05). The PAA
      occupied by ir-FSHbeta-cells was extremely high in the infantile sheep, and
      subsequently, low in the juvenile sheep (P < 0.05). Altogether, similar patterns
      of pretranslational synthesis of the LHbeta- and FSHbeta-subunit but clearly
      different storage patterns of gonadotrophins were observed. The postnatal
      development of gonadotrophins seems to be determined by the progressive increase
      in the storage of LH until peripuberty and by the acute decrease in the storage
      of FSH during the infantile/juvenile shift. These findings imply the different
      intrahypophyseal regulation of LH and FSH posttranscriptional processing during
      the period of transition between infancy and peripuberty in female sheep.

PMID- 16290078
TI  - New AAV serotypes may broaden the therapeutic pipeline to human gene therapy.

PMID- 16290077
TI  - Simulations of multi-directional forced unfolding of titin I27.
AB  - Mechanical resistance of a protein under external force is known to depend on the
      amino acid sequence, unfolding rate constant, topology and the direction of force
      applied. To assess the affect of force direction on mechanical resistance,
      molecular dynamics (MD) simulations of the partial unfolding of titin I27 have
      been carried out by applying a ramp of force between the N-terminus and the alpha
      carbon of each amino acid, respectively. The results arbitrarily place the amino
      acids in a hierarchy in terms of the time at which an unfolding intermediate is
      formed. The onset of unfolding is indeed affected by force direction; directions
      that give maximum leverage (for the A strand to detach) unfold to the
      intermediate quicker than directions that give least leverage. Moreover, the
      change in the time taken to reach the intermediate, hence the change in
      mechanical resistance, can be attributed to beta-strand topology. The simulations
      indicate that experimentally multi-directional forced unfolding could be used to
      reveal and study strand topology, and suggests that direction of applied force,
      topology and mechanical resistance are all closely related.

PMID- 16290079
TI  - The pattern of c-fos activation in the CNS is related to behavior in the
      mudskipper, Periophthalmus cantonensis.
AB  - The effects of three types of behavior on c-fos activation in different brain
      regions of the mudskipper, Periophthalmus cantonensis, were studied by
      immunocytochemistry. Animals were divided into four groups: The control group did
      not undergo any specific treatment. The second group consisted of animals that
      were agitated for an hour with a glass rod at an irregular speed. The third group
      contained animals showing aggressive behavior during an hour of monitoring, i.e.
      documented territorial hostility by raising of dorsal fins and pursuit of
      intruders. In contrast to these three groups, which had last been fed 24h
      earlier, the fourth group included animals that had been nourished 1h prior to
      sacrifice. Results showed that, in most brain regions of control animals, there
      were relatively few c-fos positive cells. After fish had been agitated, however,
      very prominent c-fos label was seen in the lateral and medial parts of the
      telencephalon, the thalamus, hypothalamus, pituitary and medulla. In aggressive
      fish, a significant increase in the number of c-fos positive sites, as compared
      to control fish, was observed in the diencephalons, pons and medulla, but not in
      the telencephalon. After feeding, there was a less substantial increase in c-fos
      protein expression in the diencephalon, but an even more prominent c-fos
      activation in the pons and medulla. Our present results support the hypothesis
      that, in fish, the medial telencephalon is involved in avoidance reaction and the
      lateral telencephalon in spatial memory, whereas rhombencephalic activation may
      reflect activity of cranial nerve nuclei.

PMID- 16290080
TI  - Proceedings of the 4th International Conference on Inhibitors of Protein Kinases
      and associated workshop: modelling of specific molecular recognition processes.
      June 25-29, 2005. Warsaw Poland.

PMID- 16290081
TI  - G148-GA3: a streptococcal virulence module with atypical thermodynamics of
      folding optimally binds human serum albumin at physiological temperatures.
AB  - The third albumin binding domain of streptococcal protein G strain 148 (G148-GA3)
      belongs to a novel class of prokaryotic albumin binding modules that is thought
      to support virulence in several bacterial species. Here, we characterize G148-GA3
      folding and albumin binding by using differential scanning calorimetry and
      isothermal titration calorimetry to obtain the most complete set of thermodynamic
      state functions for any member of this medically significant module. When
      buffered at pH 7.0 the 46-amino acid alpha-helical domain melts at 72 degrees C
      and exhibits marginal stability (15 kJ/mol) at 37 degrees C. G148-GA3 unfolding
      is characterized by small contributions to entropy from non-hydrophobic forces
      and a low DeltaCp (1.1 kJ/(deg mol)). Isothermal titration calorimetry reveals
      that the domain has evolved to optimally bind human serum albumin near 37 degrees
      C with a binding constant of 1.4 x 10 7 M(-1). Analysis of G148-GA3
      thermodynamics suggests that the domain experiences atypically small per residue
      changes in structural dynamics and heat capacity while transiting between folded
      and unfolded states.

PMID- 16290082
TI  - Overselective stimulus control in residential school students with intellectual
      disabilities.
AB  - Overselective stimulus control was assessed in 29 students at residential schools
      for individuals with developmental disabilities. Overselectivity testing included
      three different delayed identity matching-to-sample tasks. Sample stimuli for the
      Form/Color Test were nine possible combinations of three colors and three forms.
      On each trial, the S+ stimulus was identical to the sample, one S- was the same
      color as the sample but a different form, and the other S- was the same form but
      a different color. Sample stimuli for the Two-Sample Test were two alphanumeric
      characters. The S+ stimulus was identical to one of the sample stimuli, and two S
      stimuli were characters different from both samples. Sample stimuli for the
      Faces Test were six digital images of adult faces. On each trial, the S+ stimulus
      was identical to the sample, one S- stimulus was a non-matching face to which one
      sample feature had been added (e.g., an identical hat or scarf), and the other S-
      stimulus was an unaltered non-matching face. All participants were also tested
      with the Peabody Picture Vocabulary Test III (PPVT) and the Autism Diagnostic
      Observation Schedule (ADOS). Results indicated overselective stimulus control on
      at least one test for 18 of the 29 participants. Overselectivity (a) was
      distributed across a range of PPVT mental age equivalent scores from <1.75 to
      8.83; (b) was more likely in individuals with higher ADOS scores; (c) was most
      likely on the Two-Sample Test; and (d) was found in five individuals on more than
      one of the tests. Thus, overselective stimulus control may occur across a range
      of characteristics typical for students who attend residential special-education
      programs.

PMID- 16290084
TI  - Developmental changes in amniotic and allantoic fluid insulin-like growth factor
      (IGF)-I and -II concentrations of avian embryos.
AB  - In the literature, IGFs in the developing embryo are usually determined by blood
      serum concentrations. For this study, IGF-I/-II was quantified in the amniotic
      and allantoic fluids of fertile commercial broiler chicken (Gallus domesticus)
      (n=222), Pekin duck (Anas platyrhyncha) (n=250), and turkey (Meleagridis
      gallopavo) eggs (n= 200) during incubation. Amniotic and allantoic fluids were
      collected from embryos starting at 6 days of incubation for chickens and 8 days
      of incubation for ducks and turkeys. IGF concentrations within the fluids were
      determined by radioimmunoassay. Chicken amniotic IGF-I concentration at stage 29
      of development was significantly higher (P< or =0.05) than the duck or turkey. At
      stage 36 of development the concentration of IGF-II in the amniotic fluid was 2.8
      times greater in the chicken versus the duck (P< or =0.05) and 2 times greater
      than in the turkey (P< or =0.05). Within species, chicken IGF-I concentration in
      the amniotic fluid had a cubic trend (P< or =0.001), duck IGF-I increased
      linearly (P< or =0.001), and turkey concentrations declined quadratically (P< or
      =0.001) throughout development. In all species, the IGF-II concentration was
      higher than the IGF-I concentration in the amniotic and allantoic fluids.

PMID- 16290083
TI  - Temporal relationships of 21 physiological variables in horse and sheep.
AB  - Daily or circadian oscillation has been documented in a variety of physiological
      and behavioral processes. Although individual variables have been studied in
      great detail, very few studies have been conducted on the temporal relationships
      between the rhythms of different variables. It is not known whether the circadian
      pacemaker generates each and every rhythm individually or whether most rhythms
      are simply derived from a few clock-controlled rhythms. As a first step in
      elucidating this issue, 21 physiological variables were recorded simultaneously
      in horse and sheep. The results indicated that, in both species, different
      variables exhibit different degrees of daily rhythmicity and reach their daily
      peaks at different times of the day. The variables exhibiting strongest
      rhythmicity were locomotor activity, rectal temperature, and plasma
      concentrations of melatonin and glucose. Comparison of rhythmicity and acrophase
      in the various rhythms allowed inferences to be made about mechanisms of
      causation.

PMID- 16290085
TI  - The effect of sugars and free amino acids from the freshwater prawn Macrobrachium
      rosenbergii hemolymph on lectin activity and on oxidative burst.
AB  - We determined the effect of low molecular weight components (LMWC) from healthy
      juvenile and adult Macrobrachium rosenbergii hemolymph on lectin activity and
      oxidative burst (OB) in hemocytes. In an attempt to identify the LMWC that affect
      the lectin's hemagglutinating activity or oxidative burst, we determined the
      hemolymph carbohydrates and free amino acids (FAA) concentration. The LMWC (<2000
      Da) were obtained after dialysis of the hemolymph. Our results showed that LMWC
      from juveniles exerted a greater inhibition on lectin than LMWC from adult
      hemolymph. Production of superoxide radicals by hemocytes was lower in the
      presence of juvenile (p<0.05) as compared to adult LMWC. FAA composition of the
      hemolymph and of LMWC from adults showed higher proportion of alanine (which
      corresponded to 25% of total FAA) and proline (>20%); whereas, in juveniles, the
      main FAA identified were glycine (>40%) and alanine (26%). N-Acetyl-D-glucosamine
      (GlcNAc) was the main sugar residue in the hemolymph and LMWC from juveniles; its
      concentration was 2.4 times higher than glucose (Glc), whereas, in adults, Glc
      was the main free sugar residue. Our results suggest that the proportion of FAA
      and carbohydrates in the hemolymph of M. rosenbergii seems to be correlated with
      the maturation process; furthermore, the high proportion of free GlcNAc and
      glycine regulate, in the juvenile stage, lectin activity and cellular oxidative
      mechanisms, respectively.

PMID- 16290086
TI  - Segmentation of cardiac cine-MR images and myocardial deformation assessment
      using level set methods.
AB  - In this paper, we present an original method to assess the deformations of the
      left ventricular myocardium on cardiac cine-MRI. First, a segmentation process,
      based on a level set method is directly applied on a 2D + t dataset to detect
      endocardial contours. Second, the successive segmented contours are matched using
      a procedure of global alignment, followed by a morphing process based on a level
      set approach. Finally, local measurements of myocardial deformations are derived
      from the previously determined matched contours. The validation step is realized
      by comparing our results to the measurements achieved on the same patients by an
      expert using the semi-automated HARP reference method on tagged MR images.

PMID- 16290087
TI  - A pulmonary nodule modeling tool as a diagnostic aid for lung HRCT images.
AB  - A lung model and a software tool were developed with the aim to help the
      radiologist in understanding the underlying nodule distribution modes in the
      lung, in spreading nodules on lung sections according to predefined distribution
      modes. For educational purpose lung elements can be easily highlighted using
      false colors. The fast execution times which allow the radiologist to test
      different nodule distributions and to choose, by comparison with CT, the
      likeliest one, makes it a helpful tool to determine the real diagnosis. Connected
      to a database containing final diagnoses, it should be a help for research in
      lung pathology.

PMID- 16290088
TI  - Generation of gene targeting constructs for Plasmodium berghei by a PCR-based
      method amenable to high throughput applications.

PMID- 16290089
TI  - Kinetics and strain variation of phagosome proteins of Entamoeba histolytica by
      proteomic analysis.
AB  - The protozoan parasite Entamoeba histolytica ingests and feeds on microorganisms
      and mammalian cells. Phagocytosis is essential for cell growth and implicated in
      pathogenesis of E. histolytica. We report here the dynamic changes of phagosome
      proteins during phagosome maturation by proteomic analysis using reversed-phase
      capillary liquid chromatography and ion trap tandem mass spectrometry. Phagosomes
      were isolated at various intervals after internalization of latex beads.
      Immunoblot analysis and electron microscopy verified successful isolation of
      phagosomes. A total of 159 proteins were identified from the reference strain HM1
      at different stages of phagosome maturation. Approximately 70% of them were
      detected in a time-dependent fashion, suggesting dynamism of phagosome
      biogenesis. The kinetics of representative proteins were verified by immunoblots
      and also by video microscopy of live transgenic amebae expressing green
      fluorescent protein-fused EhRab7A. Furthermore, we observed significant
      differences in phagosome profiles between HM1 and two recent clinical isolates.
      Approximately 60% of 229 proteins detected in at least one of these three strains
      were identified only in one strain, while approximately 20% of these proteins
      were detected in all three strains. These data should provide significant
      insights into molecular characterization of phagosome biogenesis, and help to
      elucidate the pathogenesis of this important infection.

PMID- 16290090
TI  - Lipoic acid decreases exhaled nitric oxide concentrations in anesthetized
      endotoxemic rats.
AB  - We recently demonstrated that lipoic acid suppresses endotoxin-stimulated
      expression of inducible nitric oxide synthase and nitric oxide production in
      mouse macrophages. In this study, we tested whether lipoic acid suppresses these
      inflammatory mediators in the lungs of rats. Rats were assigned to receive either
      no special treatment, endotoxin alone, or pretreatment with lipoic acid followed
      by endotoxin. After anesthetizing the rats and injecting them intraperitoneally
      with lipoic acid (100 mg/kg) at 4 h and again at 1 h before treatment, the rats
      then received either endotoxin (0.01 mg/kg) or its vehicle solution. Exhaled gas
      was sampled every 15 min and concentrations of nitric oxide in the samples were
      measured using a chemiluminescence analyzer. After 150 min of exposure to
      endotoxin, the lungs were harvested and snap-frozen in liquid nitrogen for
      subsequent analysis. Lipoic acid attenuated endotoxin-induced increases in
      exhaled nitric oxide concentrations (P<0.001) and iNOS (P<0.05). These findings
      support the hypothesis that lipoic acid inhibits endotoxin-stimulated formation
      of intrapulmonary nitric oxide.

PMID- 16290092
TI  - Prevalence of Bartonella species, haemoplasma species, Ehrlichia species,
      Anaplasma phagocytophilum, and Neorickettsia risticii DNA in the blood of cats
      and their fleas in the United States.
AB  - Ctenocephalides felis were killed and collected from 92 cats in Alabama,
      Maryland, and Texas. The fleas and blood from the corresponding cat were digested
      and assessed in polymerase chain reaction assays that amplify DNA of Ehrlichia
      species, Anaplasma phagocytophilum, Neorickettsia risticii, Mycoplasma
      haemofelis, 'Candidatus M haemominutum' and Bartonella species. DNA consistent
      with B henselae, B clarridgeiae, M haemofelis, or 'Candidatus M haemominutum' was
      commonly amplified from cats (60.9%) and their fleas (65.2%). Results of this
      study support the recommendation to maintain flea control on cats in endemic
      areas.

PMID- 16290091
TI  - Enhanced histamine-mediated contraction of rabbit penile dorsal artery in diet
      induced hypercholesterolemia.
AB  - The present study was designed to establish whether penile dorsal arteries
      isolated from rabbits fed a high cholesterol diet show an enhanced contractile
      and/or impaired vasodilator response to histamine, and to characterize the
      histamine receptor subtype involved through in vitro isometric techniques. New
      Zealand White rabbits were fed a normal diet or a 1% cholesterol diet for 16
      weeks. Arteries from cholesterol-fed rabbits retained the ability to relax in
      response to acetylcholine, whereas histamine and noradrenaline induced a greater
      contraction response compared to that observed in controls. In both groups,
      histamine-induced contraction was unaffected by the nitric oxide synthase
      inhibitor NG-nitro-L-arginine methyl ester (L-NAME), its precursor L-arginine or
      the cyclooxygenase inhibitor indomethacin. Treatment of arterial rings in the
      control and hypercholesterolemia groups with the H1 receptor antagonist,
      mepyramine, unmasked a vasodilation response to histamine. This was followed by
      contraction at higher concentrations showing a leftward displacement of the
      histamine curve compared to controls. The histamine receptor that induced
      contraction in preparations from the hypercholesterolemic animals was of the H1
      subtype, whereas the receptor involved in histamine-induced relaxation was H2.
      The affinity of histamine receptor agonists was comparable to their effects in
      control animals, and receptor antagonists showed the same potency in both groups.
      Our findings indicate a preserved endothelial function and enhanced contraction
      in response to histamine in penile dorsal arteries, probably due to a change in
      the sensitivity of the contractile machinery of smooth muscle but not a mechanism
      mediated by a receptor.

PMID- 16290093
TI  - Autoimmune polyendocrinopathy syndrome type 1 (APS1) and AIRE gene: new views on
      molecular basis of autoimmunity.
AB  - Autoimmune polyendocrinopathy syndrome type 1 (APS1) is a monogenic autoimmune
      syndrome, which is caused by defect in AIRE gene on chromosome 21. Several
      autoimmune diseases occur in APS1 patients, often starting in first two decades
      of life. A gene defective in APS1, autoimmune regulator (AIRE), encodes nuclear
      protein involved in transcriptional processes. Recent findings in animal models
      indicate a critical role for AIRE in regulation of self-antigen expression in
      thymus. Identification of the AIRE gene, detailed characterization of molecular
      pathogenesis of human APS1 as well as analyses of mouse models carrying targeted
      interruption of Aire gene have provided new views on our understanding of
      molecular background of autoimmunity.

PMID- 16290094
TI  - A pragmatic 2 x 2 x 2 factorial cluster randomized controlled trial of
      educational outreach visiting and case conferencing in palliative care
      methodology of the Palliative Care Trial [ISRCTN 81117481].
AB  - The demand for palliative care is increasing, yet there are few data on the best
      models of care nor well-validated interventions that translate current evidence
      into clinical practice. Supporting multidisciplinary patient-centered palliative
      care while successfully conducting a large clinical trial is a challenge. The
      Palliative Care Trial (PCT) is a pragmatic 2 x 2 x 2 factorial cluster randomized
      controlled trial that tests the ability of educational outreach visiting and case
      conferencing to improve patient-based outcomes such as performance status and
      pain intensity. Four hundred sixty-one consenting patients and their general
      practitioners (GPs) were randomized to the following: (1) GP educational outreach
      visiting versus usual care, (2) Structured patient and caregiver educational
      outreach visiting versus usual care and (3) A coordinated palliative care model
      of case conferencing versus the standard model of palliative care in Adelaide,
      South Australia (3:1 randomization). Main outcome measures included patient
      functional status over time, pain intensity, and resource utilization.
      Participants were followed longitudinally until death or November 30, 2004. The
      interventions are aimed at translating current evidence into clinical practice
      and there was particular attention in the trial's design to addressing common
      pitfalls for clinical studies in palliative care. Given the need for evidence
      about optimal interventions and service delivery models that improve the care of
      people with life-limiting illness, the results of this rigorous, high quality
      clinical trial will inform practice. Initial results are expected in mid 2005.

PMID- 16290095
TI  - Life expectancy at the age of 65 years and environmental factors: an ecological
      study in Japan.
AB  - The purpose of this study was to examine the factors associated with life
      expectancy at the age of 65 years used as the index of longevity, using published
      data in Japan. Life expectancy at the age of 65 years was obtained from the 19th
      life table in 2000 published by the Ministry of Health, Labour and Welfare of
      Japan. The associations between life expectancy at the age of 65 years and
      environmental factors were assessed by Spearman correlation coefficients. Life
      expectancy at the age of 65 years was higher in females (22.54 years) than in
      males (17.42 years). In this study, the number of public health nurses and
      leisure time per day were found significantly associated with life expectancy at
      the age of 65 years in both men and women. For men, life expectancy at the age of
      65 years was significantly associated with leisure time for sports and exercises
      and higher proportion of participation in volunteer activities in the community;
      for women, it was associated with a higher number of hospitals and proportion of
      participation in educational classes for the aged. Our ecological study might
      provide some clues to more practical planning for longevity in consideration of
      gender differences.

PMID- 16290096
TI  - Effect of ultrasound on desorption kinetics of phenol from polymeric resin.
AB  - This work mainly involves the study of desorption kinetics of phenol from
      polymeric resins under the influence of an ultrasound field. A new phase
      equilibrium-kinetics model (PEKM), for estimation of diffusion coefficient was
      proposed, kinetic experiments of phenol desorption on NKA-II resin in the
      presence and the absence of ultrasound were separately conducted, and diffusion
      coefficients of phenol within an adsorbent particle were estimated by means of
      proposed PEKM. Results showed that the use of ultrasound could enhance the
      diffusion of phenol within the resin. The diffusion coefficient of phenol in the
      resin in an ultrasonic field increased by an order of magnitude in comparison
      with the diffusion coefficient in the absence of ultrasound. The more intense the
      ultrasonic field the larger was the diffusion coefficient.

PMID- 16290097
TI  - Coordination of ER and oxidative stress signaling: the PERK/Nrf2 signaling
      pathway.
AB  - In the broadest sense, cellular stress describes conditions wherein cells
      encounter and react to a 'non-normal' state. Perturbations may originate through
      both extracellular and intracellular means. Whereas transient levels of stress
      are expected to occur on a regular basis, a series of checks and balances ensures
      that cells are well equipped to maintain a homeostatic state. In the case of
      supra-physiological stress signaling, cellular challenges are more severe, and
      programmed cell death may be the best option for the organism. The ability of a
      cell, and by extension, an organism, to adequately manage cellular stress is
      fundamental--a question of life or death. The endoplasmic reticulum (ER) is
      exquisitely poised to sense and respond to cellular stresses including those that
      result from metabolic and/or protein folding imbalances. In response to stress
      originating from within the ER, the PERK and Ire1 protein kinases, along with
      other proximal signaling molecules, initiate a program of transcriptional and
      translational regulation termed the unfolded protein response. A consequence of
      ER stress is the accumulation of reactive oxygen species that promotes a state of
      oxidative stress. PERK signaling, via activation of the Nrf2 and ATF4
      transcription factors, coordinates the convergence of ER stress with oxidative
      stress signaling. Here we discuss progress regarding the signaling pathways
      involved in these cellular stresses and the implications of the intersection
      between the two signaling pathways.

PMID- 16290098
TI  - Cell transplantation: differential effects of myoblasts and mesenchymal stem
      cells.
AB  - BACKGROUND: Cellular transplantation has emerged as a novel therapeutic option
      for treatment of ventricular dysfunction. Both skeletal myoblasts (SM) and
      mesenchymal stem cells (MSC) have been proposed as ideal cell for this aim. The
      aim of this study is to compare the efficacy of these cells in improving
      ventricular function and to evaluate the different histological findings in a rat
      model of severe post-infarct ventricular dysfunction. METHODS: Myocardial
      infarction was induced in Wistar rats by left coronary occlusion. Animals with
      resulting ejection fraction (EF) lower than 40% were included. Heterologous SM
      were obtained by lower limb muscle biopsy and MSC by bone marrow aspiration. Nine
      days after infarction, rats received intramyocardial injection of SM (n=8), MSC
      (n=8) or culture medium, as control (n=11). Echocardiographic evaluation was
      performed at baseline and after 1 month. Histological evaluation was performed
      after HE and Gomori's trichrome staining and immunostainig against desmin, fast
      myosin and factor VIII. RESULTS: There was no difference in baseline EF and left
      ventricular end diastolic (LVEDV) and systolic volume (LVESV) between all groups.
      After 1 month a decrease was observed in the EF in the control group (27.0+/
      7.10% to 21.46+/-5.96%, p=0.005) while the EF markedly improved in SM group
      (22.66+/-7.29% to 29.40+/-7.01%, p=0.04) and remained unchanged in the MSC group
      (23.88+/-8.44% to 23.63+/-10.28%, p=0.94). Histopathology identified new muscular
      fibers in the group that received SM and new vessels and endothelial cells in the
      MSC. CONCLUSION: Skeletal myoblasts transplantation resulted in myogenesis and
      improvement of ventricular function. In contrast, treatment with mesenchymal stem
      cells resulted in neoangiogenesis and no functional effect.

PMID- 16290099
TI  - Utility of triple channel injection of contrast material with mixture of saline,
      with acquisition in the cephalic direction for arterial trees in the thorax using
      multislice computed tomography.
AB  - BACKGROUND: If contrast material is injected into the cubital vein, artifacts due
      to high concentration of the contrast material in the vein lead to deterioration
      of the opacification of the thoracic aorta and the major branches. We describe a
      new protocol employing a combination of triple channel contrast material
      injection and a mixture of saline with acquisition in the cephalic direction
      utilizing capability of 16-slice multislice CT. MATERIALS AND METHODS: Of 35
      subjects who underwent thoracic CT, 18 were injected with 70 ml contrast each
      prior to scanning with acquisition in the cephalic direction during the injection
      of 30 ml contrast diluted 50/50 with saline, followed by the injection of 20 ml
      of saline (new protocol). Seventeen subjects were injected each with 100 ml
      contrast at 3 ml/s, with scanning in the caudal direction (ordinary protocol).
      RESULTS: In the new protocol, the major branches of the aorta and the left
      ventricle were more opacified, but the veins were less opacified compared with
      the ordinary protocol, resulting in clear delineation of the thoracic aorta and
      the major branches without artifacts. CONCLUSIONS: A new acquisition protocol is
      described in which the thoracic aorta and the major branches can be evaluated
      without artifact due to high CT values in the veins. Faster, more informative CT
      scans can be performed using diluted contrast.

PMID- 16290100
TI  - Association of lipid profile with echocardiographic Wilkins score in patients
      with moderate to severe mitral stenosis: possible impact on prognosis.
AB  - BACKGROUND: Association of valvular heart disease and lipid profile might be
      important as in the case of aortic stenosis. However, it has not been so far
      considered in detail the probable association of other valvular diseases,
      particularly of mitral stenosis (MS) with lipid profile. In our study, we aimed
      to search possible association of echocardiographic mitral valve score, evaluated
      according to Wilkins score, with lipid parameters in a group of patients with
      mitral stenosis, who were referred for possible percutaneous balloon
      valvuloplasty. MATERIAL AND METHOD: We retrospectively reviewed 401 patients (316
      female, 85 male), who were referred as possible candidates for PMBV, with
      moderate to severe MS of predominantly rheumatic origin. Mitral valve was
      evaluated according to Wilkins score by an experienced author as indicated.
      RESULTS: Mean age of all patients was 36.6+/-11.3 years, and was not different in
      both genders. Mean mitral valve area was 1+/-0.1 mm2. Considering all patients,
      total Wilkins score was significantly, but mildly correlated with ratio of
      total/HDL cholesterol ratio (r=0.174, p=0.02). Presence of more than one
      recurrent attack of rheumatic fever, narrow mitral valve area, high total/HDL
      cholesterol and being male were independent predictors of poor echocardiographic
      Wilkins score (>8). CONCLUSION: We think that Wilkins echocardiographic score of
      mitral stenosis, particularly of leaflet thickening, might well be associated
      with serum lipids, probably as the same extent does aortic stenosis.

PMID- 16290101
TI  - Correlation of plasma N-terminal pro-brain natriuretic peptide levels with left
      ventricle mass in children treated with anthracyclines.
AB  - BACKGROUND: The incidence of subclinical cardiotoxicity following anthracycline
      treatment for childhood cancer varies according to the method used for its
      detection. The aim of the study was to document the prevalence of left
      ventricular myocardial mass (LVM) reduction and its possible association with
      plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in
      asymptomatic children treated with anthracyclines. PATIENTS AND METHODS: Nineteen
      asymptomatic children who had received anthracyclines during their treatment for
      cancer were evaluated. They had received an equivalent of doxorubicin dose 240
      mg/m2 (22-1200 mg/m2) on average 3.9 years (0.6-8.3) before (median age at
      diagnosis 3.8 years). The LVM was determined by M-Mode echocardiography and
      compared to the expected value, obtained from the regression equation of LVM on
      height of a group of 160 healthy children. Additionally the patients' plasma NT
      pro BNP levels were determined. RESULTS: A high prevalence of reduced LVM
      associated with increased NT-proBNP levels was found. The average LVM value was 
      14.4% (+/-4.9) lower than expected whereas fourteen patients (73%) had a lower
      LVM than predicted. The NT-pro BNP levels in patients with reduced LVM were
      significantly higher than those measured in patients without LVM reduction
      (0.316+/-0.02 versus 0.17+/-0.01 pmol/ml respectively, p=0.009). A cut off NT-pro
      BNP level of 0.2 pmol/ml could differentiate patients with LVM reduction from
      those with normal or greater than expected LVM. CONCLUSION: The association of
      higher NT-proBNP levels with reduced LVM in asymptomatic children after
      anthracycline administration could be an early indication of subclinical
      cardiotoxicity.

PMID- 16290102
TI  - Total anomalous pulmonary venous return in the fourth decade.
AB  - Most patients with total abnormal venous connection (TAPVC) have no symptoms at
      birth, yet the majority die within the first year of life if surgical repair is
      not implemented. TAPVC is usually suspected in the neonatal period, and without
      surgical repair prolonged survival is quite exceptional. This kind of abnormality
      can be a real challenge for a non-pediatrics cardiologist today and can be easily
      misdiagnosed as a large secundum atrial septal defect if there is no sufficient
      suspicion of TAPVC. Therefore, a case of a 40-year-old female patient referred to
      our clinic with increasing shortness of breath is of great interest, as this
      patient was diagnosed with TAPVC.

PMID- 16290103
TI  - Obesity, Hippocrates and Venus of Willendorf.

PMID- 16290104
TI  - Prognostic effect of renal dysfunction after ST-segment elevation myocardial
      infarction with and without heart failure.
AB  - PURPOSE: The present study was designed to assess, 1) the independent prognostic
      effect of renal dysfunction on all-cause mortality in the setting of acute
      myocardial infarction with ST-segment elevation (STEMI), and 2) to determine if
      such effect varies based upon the presence of heart failure (HF) on admission.
      METHODS: 549 consecutive patients admitted with the diagnosis of STEMI were
      prospectively recruited in a teaching hospital in Spain. Serum creatinine (sCr)
      and glomerular filtration rate (GFR) were obtained on admission, together with
      other relevant information used for risk stratification. The independent effect
      of sCr and GFR on long-term mortality was determined by Cox regression analysis.
      Main outcome was all-cause mortality, with a median follow-up of 1 year. RESULTS:
      In a multivariate analysis the degree of renal impairment was a strong predictor
      of mortality in patients without clinical evidence of HF at admission (HR=1.15;
      95% CI 1.10 to 1.19 and HR=1.58; 95% CI 1.30 to 1.81) for sCr (per 0.1 mg/dl) and
      GFR (per decreasing 10 ml/min/1.73 m2), respectively. In the group with HF, the
      effect was less pronounced (HR=1.03; 95% CI 1.01 to 1.04 and HR=1.17; 95% CI 1.02
      to 1.37) for sCr and GFR, respectively. CONCLUSIONS: In the setting of STEMI,
      renal dysfunction estimates showed a differential prognostic effect depending on
      HF status, with a greater impact seen in patients without clinical evidence of
      HF.

PMID- 16290105
TI  - Elevated troponin level is not synonymous with myocardial infarction.
AB  - BACKGROUND: Elevated troponin I in the absence of angiographically visible
      coronary lesions is seen in up to 10-15% of those undergoing angiography for
      suspected coronary artery disease. This study aims to elucidate the etiology of
      elevated cardiac troponin I in patients with normal coronary arteries on
      angiography. METHODS: We identified 1551 (8.6%) patients with normal coronary
      arteries from our catheterization database of 17,950 patients from Jan 2000 to
      Jun 2004. Elevated troponin I levels were found in 217 (14%) of 1551 patients
      with normal coronary arteries. Of these 217 patients, 73 surgical patients were
      excluded, and the remaining 144 patients formed the study population. The study
      population was compared with age and gender matched patients with myocardial
      infarction and coronary artery disease (Group II). RESULTS: The patients with
      elevated cardiac troponin I (cTnI) with normal coronary arteries had
      significantly lower prevalence of atherosclerotic risk factors and significantly
      higher left ventricular ejection fractions. The cTnI in patients with normal
      coronary arteries was elevated due to a number of causes including tachycardia,
      myocarditis, pericarditis, severe aortic stenosis, gastrointestinal bleeding,
      sepsis, left ventricular hypertrophy, severe congestive heart failure,
      cerebrovascular accident, electrical trauma, myocardial contusion, hypertensive
      emergency, myocardial bridging, pulmonary embolism, diabetic ketoacidosis,
      chronic obstructive pulmonary disease exacerbation and coronary spasm.
      CONCLUSIONS: Cardiac troponin I could be elevated in a number of conditions,
      apart from acute myocardial infarction, and could reflect myonecrosis. Acute
      myocardial infarction is a clinical diagnosis as the laboratory is an aide to,
      not a replacement for, informed decision making.

PMID- 16290106
TI  - Activation of pyramidal cells in rat medial prefrontal cortex projecting to
      ventral tegmental area by a 5-HT1A receptor agonist.
AB  - 5-HT(1A) receptor agonists increase the activity of dopamine (DA) neurons in the
      ventral tegmental area (VTA) and DA release in medial prefrontal cortex (mPFC).
      The mPFC is enriched in 5-HT(1A) receptors and projects to the VTA, where
      mesocortical dopaminergic neurons originate. We examined whether 5-HT(1A)
      receptor activation can modulate the activity of mPFC pyramidal neurons
      projecting to VTA. These were identified by antidromic stimulation from the VTA
      and were recorded extracellularly in anesthetized rats. The selective 5-HT(1A)
      agonist BAY x 3,702 (10-80 microg/kg i.v.) increased the firing rate in 14/19
      neurons (283 +/- 79%) and reduced the activity of 5/19 neurons (22 +/- 11%),
      resulting in an overall 2.2-fold increase of the firing rate. Both effects were
      blocked by the selective 5-HT(1A) antagonist WAY-100635. These results suggest
      that the increase in dopaminergic activity produced by 5-HT(1A) receptor
      activation can be driven by an increase in the activity of projection neurons in
      mPFC.

PMID- 16290107
TI  - The effect of oxidative metabolism on spontaneous Pol zeta-dependent translesion
      synthesis in Saccharomyces cerevisiae.
AB  - DNA lesions can stall or block high-fidelity polymerases, thus inhibiting
      replication. To bypass such lesions, low-fidelity translesion synthesis (TLS)
      polymerases can be used to insert a nucleotide across from the lesion or extend
      from a lesion:base mispair. When DNA repair is compromised in Saccharomyces
      cerevisiae, spontaneous DNA lesions can lead to a novel mutational event in which
      a frameshift is accompanied by one or more base pair substitutions. These
      "complex frameshifts" are dependent upon the TLS polymerase Pol zeta, and provide
      a mutational signature for mutagenic Pol zeta-dependent activity. In the current
      study, we have found that a specific subset of the Pol zeta-dependent mutational
      events requires oxidative metabolism. These results suggest that translesion
      bypass of spontaneously oxidized DNA bases can be a significant source of
      mutagenesis in repair compromised cells.

PMID- 16290108
TI  - Recent cannabis abuse decreased stress-induced BOLD signals in the frontal and
      cingulate cortices of cocaine dependent individuals.
AB  - Previous neuroimaging studies showed that use of marijuana can alter patterns of
      cortical activation during rest or a task challenge. We used functional magnetic
      resonance imaging to examine whether recent cannabis abuse contributed to stress
      induced blood-oxygen-level-dependent (BOLD) contrast in a group of cocaine
      dependent individuals. Emotional stress was induced using the script-guided
      imagery paradigm, in which subjects imagined being in a real-life stressful
      situation and, as a control, in a neutral situation, while BOLD signals of their
      brain were acquired with a 1.5 T scanner. Abstinent cocaine-dependent subjects
      with recent marijuana abuse (n=8) were compared with abstinent cocaine-dependent
      subjects who had not abused marijuana recently (n=18). The two groups were
      otherwise matched in their demographic characteristics and drug use history. All
      subjects were abstinent for at least 15 days and drug free as confirmed by urine
      drug screening before the imaging session. Recent cannabis abusers demonstrated
      hypo-activation in frontal cortical areas including the perigenual anterior
      cingulate during increased emotional stress. In contrast, at the same statistical
      threshold, no brain regions showed increased activation in recent cannabis
      abusers compared with non-abusers. The group difference in the perigenual
      anterior cingulate remained even when lifetime cocaine and alcohol consumption
      was accounted for in covariance analysis. These results provide evidence that
      recent cannabis abuse is associated with decreased activation in the frontal
      cortex during an emotional stress task. The results suggest an abnormal cognitive
      control mechanism during affective processing in association with heavy cannabis
      use.

PMID- 16290109
TI  - Preparation and crystallization of the disulfide-linked HLA-G dimer.
AB  - HLA-G is a non-classical MHC class I, which binds to inhibitory receptors, such
      as Leukocyte Ig-like receptors, to induce a wide range of tolerogenic
      immunological effects. HLA-G can be expressed as a disulfide-liked dimer both in
      solution and at the cell surface. However, the three-dimensional structure of the
      HLA-G dimer is unknown. Here, we report the crystallization of the disulfide
      linked dimer form of HLA-G by adding dithiothreitol (DTT), enabling a 3.2-A data
      set to be collected. We also show that DTT promotes disulfide bond exchange of
      refolded HLA-G, whose free cysteine was protected, thus facilitating its
      dimerization. This technique could also be applied for disulfide-mediated
      dimer/multimer formation of refolded proteins harbouring free cysteines.

PMID- 16290111
TI  - Endogenous longevity, biological deterioration and economic growth.
AB  - The identification of the types of bidirectional interactions that take place
      between longevity and economic growth in the long-run is carried out by means of
      the integration of human capital accumulation, innovation in medical technology,
      a health goods sector, and individual decisions on health and longevity in a
      dynamic general equilibrium set-up. In this context, in which individual agents
      decide not only on their "quality" of life but also on its "quantity", the mere
      process of biological deterioration, that is to say, the continuous loss of
      health goods effectiveness in maintaining a given level of health as individuals
      age, provides the reason for an additional, and new, engine of growth.

PMID- 16290110
TI  - The early history of TGF-beta, and a brief glimpse of its future.

PMID- 16290113
TI  - The influence of nickel on the adhesion ability of Desulfovibrio desulfuricans.
AB  - The build-up of biofilms on metals surfaces may lead to severe corrosion,
      especially in the presence of sulphate-reducing bacteria (SRB). To prevent the
      deterioration of material caused by biofilms it is necessary to understand the
      processes governing biofilm development including mechanisms of cell adhesion.
      Additionally, corrosion of metallic surfaces due to bacteria may lead to the
      dissolution of metallic elements that may further affect adhesion and biofilm
      development. A study was carried out to evaluate how the presence of nickel in
      the substrata affects the adhesion ability of Desulfovibrio desulfuricans. The
      substrata tested were stainless steel 304 (SS), metallic nickel (Ni) and
      polymethylmetacrylate (PMMA), a non-metallic material used as control. The
      influence of nickel on SRB growth and its relation to adhesion was also checked.
      A statistically significant difference in the number of adhered cells to the
      materials tested was detected, with higher bacterial number on nickel, followed
      by SS and finally by PMMA. The higher number of SRB adhered to steel compared
      with PMMA may be explained by differences in hydrophobicity, in roughness and in
      the electron-acceptor character of the substrata. Additionally, bacterial growth
      was found to be positively affected by the presence of nickel as revealed by a
      significant increase in the specific growth rate of SRB in the presence of
      increased nickel concentrations.

PMID- 16290112
TI  - A rapid method for extracting oocyst DNA from Cryptosporidium-positive human
      faeces for outbreak investigations.
AB  - We describe a rapid method for extracting and concentrating Cryptosporidium
      oocysts from human faecal samples with subsequent DNA preparation for mainstream
      PCR applications. This method consists of extracting faecal lipids using a
      modified water-ether treatment and releasing DNA from semi-purified oocysts by
      freeze thawing in lysis buffer. Following immunomagnetisable separation (IMS),
      recovery rates of 29.5%, 43.2% and 49.8% were obtained from oocyst-negative
      solid, semi-solid and liquid faeces, respectively, seeded with 100 +/- 2 C.
      parvum oocysts, which were enumerated by flow cytometry. A retrospective analysis
      was conducted on 92 positive human faecal samples including 78 oocyst-positive
      cases from 2 UK cryptosporidiosis outbreaks (outbreak A = 34 samples, outbreak B
      = 44 samples) and 14 oocyst-positive, sporadic cases. We used primers targeting
      the Cryptosporidium oocyst wall protein gene (COWP; STN-COWP), the 18S rRNA
      (direct PCR) and the dihydrofolate reductase gene (dhfr, MAS-PCR) fragments to
      evaluate extracted DNA by PCR. PCR inhibitors were present in 20 samples when
      template was co-amplified with the 18S rRNA gene primers and an internal control.
      Template dilution (1/5) in polyvinylpyrrolidone (10 mg ml(-1), pH 8.0)
      transformed four PCR-negative samples to PCR-positive and increased amplicon
      intensity in previously positive samples. Eighteen of 20 PCR-negative samples
      produced visible amplicons when Taq polymerase concentration in the STN-COWP PCR
      was increased from 2.5 to 5 U. The STN-COWP PCR assay amplified 90 of 92 samples
      (97.8%) and the MAS-PCR assay amplified 70 of 92 samples (76.1%) tested. In the
      absence of inhibitors, DNA equivalent to 3 C. parvum oocysts was amplified.

PMID- 16290114
TI  - Dietary PUFA modulate the expression of proliferation and differentiation markers
      in Morris 3924A hepatoma cells.
AB  - The effect of dietary polyunsaturated fatty acids on the expression of
      differentiation and proliferation markers in Morris 3924A hepatoma cells was
      investigated. ACT/I rats were conditioned 10 days with diets enriched with
      linoleic acid or alpha-linolenic acid before subcutaneous hepatoma cell
      transplantation. After 19 days from the inoculum, the mRNA levels of liver
      enriched transcription factors and of their target genes were quantified. Both
      linoleic acid- and linolenic acid-enriched diets induced a decrease of beta
      actin, AFP, PCNA, c-myc and of hepatocyte nuclear factors HNF-1alpha and HNF
      4alpha mRNA levels in tumor tissue whereas HNF-3beta expression was induced by
      both dietary treatments. Only the alpha-linolenic acid-enriched diet was
      effective in reducing c-jun and increasing albumin mRNA levels. Since albumin is
      a C/EBPalpha target gene, C/EBPalpha gene transcription was evaluated at both
      protein and mRNA levels. It was found that alpha-linolenic acid-enriched diet did
      not enhance the C/EBPalpha mRNA content in hepatoma tissue while inducing
      C/EBPalpha protein expression with an isoform pattern similar to the hepatic
      phenotype. This evidence implies that alpha-linolenic acid or one of its
      metabolic products induce albumin synthesis in hepatoma cells by modulating
      C/EBPalpha gene expression at post-transcriptional level.

PMID- 16290115
TI  - When sound and picture do not fit: Mismatch negativity and sensory interaction.
AB  - The Mismatch Negativity (MMN), an index of auditory stimulus representation, was
      studied in a design of simultaneous auditory and visual stimulus presentation. A
      counting task drew the attention of participants to picture presentation and was
      unrelated to the occurring sounds. With the picture of a hammer hitting a nail a
      standard sound "bang" came along. Rarely, a deviant picture showed the hammer
      hitting the finger combined with a corresponding deviant sound "ouch." Sometimes
      this deviant picture was combined with the standard sound. In spite of the
      absence of a sound deviancy to the standard sounds, also in the latter case a
      significant MMN was detected, indicating that the actual visual context affected
      the incoming auditory information leading to a mismatch with the prevailing
      auditory memory trace. Herewith, MMN gains importance as an index of auditory
      stimulus representation also in studies of sensory interaction.

PMID- 16290116
TI  - Impact of chronic heart failure on elderly persons' daily life: a validation
      study.
AB  - BACKGROUND: Knowledge about how elderly persons perceive the impact of chronic
      heart failure (CHF) on daily life is important when planning nursing care. For
      this purpose, disease specific instruments are needed. However, few instruments
      have been developed or tested specifically on elderly persons. AIM: To validate a
      Swedish version of the Minnesota Living with Heart Failure Questionnaire (LHFQ)
      on elderly persons with CHF, and use it to describe the impact of CHF on daily
      life in the same population. METHODS: The sample comprised of 357 persons, aged
      between 65 and 99, diagnosed with CHF. A questionnaire including background data,
      the LHFQ and the SF-12 was used. RESULTS: A factor analysis resulted in four
      dimensions: physical, emotional, treatment and pleasure. LHFQ showed convergent
      validity and ability to discriminate between known groups. Cronbach's alpha for
      the total scale was 0.94. Impairments in the physical dimension were most common,
      especially fatigue (88%) and shortness of breath (87%). CONCLUSIONS: The LHFQ
      showed satisfying psychometric properties in an elderly Swedish population with
      CHF and can, with minor alterations, be recommended for research and clinical
      use. The impact of chronic heart failure on daily life was mostly physical, but
      other impairments were also common.

PMID- 16290117
TI  - Charting epilepsy by searching for intelligence in network space with the help of
      evolving autonomous agents.
AB  - The problem of demarcating neural network space is formidable. A simple fully
      connected recurrent network of five units (binary activations, synaptic weight
      resolution of 10) has 3.2 *10(26) possible initial states. The problem increases
      drastically with scaling. Here we consider three complementary approaches to help
      direct the exploration to distinguish epileptic from healthy networks. [1] First,
      we perform a gross mapping of the space of five-unit continuous recurrent
      networks using randomized weights and initial activations. The majority of weight
      patterns (>70%) were found to result in neural assemblies exhibiting periodic
      limit-cycle oscillatory behavior. [2] Next we examine the activation space of non
      periodic networks demonstrating that the emergence of paroxysmal activity does
      not require changes in connectivity. [3] The next challenge is to focus the
      search of network space to identify networks with more complex dynamics. Here we
      rely on a major available indicator critical to clinical assessment but largely
      ignored by epilepsy modelers, namely: behavioral states. To this end, we
      connected the above network layout to an external robot in which interactive
      states were evolved. The first random generation showed a distribution in line
      with approach [1]. That is, the predominate phenotypes were fixed-point or
      oscillatory with seizure-like motor output. As evolution progressed the profile
      changed markedly. Within 20 generations the entire population was able to
      navigate a simple environment with all individuals exhibiting multiply-stable
      behaviors with no cases of default locked limit-cycle oscillatory motor behavior.
      The resultant population may thus afford us a view of the architectural
      principles demarcating healthy biological networks from the pathological. The
      approach has an advantage over other epilepsy modeling techniques in providing a
      way to clarify whether observed dynamics or suggested therapies are pointing to
      computational viability or dead space.

PMID- 16290118
TI  - Colon-specific 9-aminocamptothecin-HPMA copolymer conjugates containing a 1,6
      elimination spacer.
AB  - N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer-9-aminocamptothecin (9-AC)
      conjugate for oral colon-specific drug delivery was designed, synthesized, and
      characterized. The drug, 9-AC, was attached to the polymer carrier via a spacer
      containing a combination of an aromatic azo bond and a 4-aminobenzylcarbamate
      group. The design of the spacer ensured a fast and highly efficient release of
      unmodified 9-AC from the polymer in the colon by azo bond cleavage followed by a
      1,6-elimination mechanism. An in vitro degradation study indicated that this
      conjugate was stable in simulated upper GI tract conditions, including small
      intestine (SI) contents, SI mucosa suspension, and in PBS (pH 1.5 and 7.4). A
      fast release of the unmodified drug (85+/-10% of 9-AC in 12 h) was detected in
      rat cecal contents. This drug delivery system has potential in the treatment of
      colon cancer.

PMID- 16290119
TI  - Covalent immobilization of RGDS on hydrogel surfaces to direct cell alignment and
      migration.
AB  - This study extends the capability for directing cell behavior using PEG-based
      hydrogels in tissue-engineering applications to include control over the spatial
      distribution of the adhesive peptide, RGDS. A continuous linear gradient was
      formed by simultaneously using a gradient maker to combine precursor solutions
      and using photopolymerization to lock the RGDS gradient in place. Hydrogels
      containing entrapped gradients of bovine serum albumin (BSA) were characterized
      using Coomassie brilliant blue stain, which indicated that BSA concentration
      increases along the hydrogel's length and that the steepness of the gradient's
      slope can be varied by changing the relative BSA concentrations in the precursor
      solutions. Human dermal fibroblasts responded to covalently immobilized RGDS
      gradients by changing their morphology to align in the direction of increasing
      RGDS concentration. After 24 h, approximately 46% of fibroblasts were aligned
      with the RGDS-gradient axis. This proportion of cells further increased to
      approximately 53% (p < 0.05) and approximately 58% after 48 and 96 h,
      respectively. Also, fibroblasts migrated differentially depending on the
      concentration of RGDS. Fibroblasts migrated approximately 48% further going up
      the concentration gradient (0 to 6 micromol/ml PEG-RGDS) than going down the
      concentration gradient. Migration up the concentration gradient was also
      approximately 33% greater than migration on control surfaces with a constant
      concentration of RGDS (2 micromol/ml), while migration down the gradient was
      reduced approximately 12% relative to the control surface. In addition, directed
      migration was further enhanced by increasing the RGDS gradient's slope. This
      hydrogel system is expected to be useful for directing cell migration to enhance
      the formation of engineered tissues.

PMID- 16290120
TI  - An EPR and ENDOR study of gamma- and beta-radiation sterilization in poly
      (lactide-co-glycolide) polymers and microspheres.
AB  - EPR/ENDOR spectroscopy was used to characterise the free radicals generated in a
      series of PLGA raw polymers and microspheres (with lactide:glycolide compositions
      of (75:25), (65:35) and (50:50)) after exposure to gamma (gamma-) and electron
      beam (beta-) irradiation at room temperature. Both sets of irradiated samples
      produced analogous EPR spectra, indicating that the type and distribution of free
      radicals generated by gamma-irradiation are similar to those generated by beta
      irradiation. The radicals were identified by EPR simulations as the chain
      scission species -(CHO-(approximately 27% abundance),-C(CH(3))O- ( approximately
      23% abundance) and the terminal-C(CH(3))-OR fragment (approximately 50%
      abundance), and these assignments were supported by the ENDOR analysis. The
      latter two radical species were demonstrated to originate from the lactide
      component of the PLGA polymer. Overall systematically higher radical
      concentrations were found as the lactide content of the PLGA raw polymer and
      microspheres increases (ie., 75:25 > 65:35 > 50:50) for both gamma- and beta
      irradiation. However, while the relative concentrations of free radicals was
      similar in the raw polymer samples after exposure to gamma- or beta-irradiation,
      a substantial difference was found for the microsphere samples; an approximate
      doubling of the radical content was found in the gamma-irradiated PLGA
      microspheres compared to the identical beta-irradiated microspheres.

PMID- 16290121
TI  - Amelioration of experimental colitis by Copaxone is associated with class-II
      restricted CD4 immune blocking.
AB  - Copaxone modifies TH1 immune response in multiple sclerosis. As Crohn's disease
      shares TH1 predominance, this study came to investigate the anti-inflammatory
      response of Copaxone in animal model of colitis. METHODS: Colitis was induced by
      intra-rectal instillation of TNBS in 2 animal groups; one of them was daily
      treated intraperitoneally by 300 mug Copaxone starting 48 h post-colitis
      induction. Both colitis groups were compared to naive group. Eight male C57Bl6
      mice were used in each group. At day 12, distal colon was excised for standard
      scoring, splenocytes were isolated for FACS and serum cytokines were assessed.
      Splenocytes were in-vitro-stimulated with colitis protein extracts in the
      presence or absence of Copaxone. Lymphocytes were blocked by either MHC anti
      class I or anti-class II antibodies prior to Copaxone administration. RESULTS:
      Copaxone markedly alleviated macro/microscopic colitis scoring as they decreased
      from 2.9 +/- 1.1/2.6 +/- 0.8 in colitis group to 1.7 +/- 1/1.5 +/- 0.5 in
      Copaxone-treated mice (P = 0.03/P = 0.008, respectively) compared to 0 +/- 0/1 +/
      0 in naives (P < 0.001/P < 0.01, respectively). CD4 subsets significantly
      decreased following Copaxone administration as compared to naive mice (P = 0.05).
      Although Copaxone-treated mice manifested a block of both serum TH1/TH2
      responses, only interferon gamma secreting CD4 cells significantly decreased. NK
      cells tend to increase following colitis induction (P = 0.08), however, they
      significantly decreased in Copaxone-treated animals (P = 0.006). NK-T followed NK
      pattern. Using in vitro studies, Copaxone showed amelioration of T-cell
      proliferation that was significantly blocked when cells were pre-incubated with
      anti-MHC class II but not class I antibodies. CONCLUSIONS: Copaxone had class-II
      restricted anti-inflammatory effect in our animal colitis model associated with
      CD4/NK/NKT/TH1/TH2 suppression.

PMID- 16290122
TI  - Solid lipid nanoparticles can effectively bind DNA, streptavidin and biotinylated
      ligands.
AB  - Cationic solid lipid nanoparticles (SLN) have recently been suggested for non
      viral gene delivery, as these particles consist of well tolerated substances, can
      bind DNA directly via electrostatic interactions and mediate gene transfer in
      vitro. We here report the development of SLN complexes, which can be targeted to
      specific surface receptors. A formulation of SLN was prepared by the
      microemulsion technique comprising of stearylamine and the matrix lipid Compritol
      ATO 888 with a size of approximately 100 nm and a zeta-potential of +15. These
      SLN are able to condense DNA in complexes, which are very stable under
      physiological conditions, and they display low cytotoxicity in cell culture. In
      addition to binding of DNA, the SLN can simultaneously bind substantial amounts
      of streptavidin directly via electrostatic interactions. The SLN:DNA:
      streptavidin complexes are stable and are capable of binding biotinylated
      ligands, which can interact with surface receptors. This method allows for
      development of a fast and simple method of preparing a targeted non-viral gene
      therapy vector.

PMID- 16290123
TI  - Differential effects of RAS inhibitors associated with ACE gene polymorphisms in
      type 2 diabetic nephropathy.
AB  - Blood pressure and genetic factors are important factors for diabetic
      nephropathy. We investigated the relationship between the efficacy of renin
      angiotensin system (RAS) inhibitors and angiotensin-converting enzyme (ACE)
      genotypes. Patients with type 2 diabetes without proteinuria, were treated with
      RAS inhibitors, the first being an ACE inhibitor (ACEI) and the second, an
      angiotensin II (ATII) receptor blocker (ARB) for 8 weeks each. There was no
      significant difference (except serum ACE activity) between the two treatments.
      However, by analysis segregated with ACE gene polymorphism, ARB significantly
      decreased transforming growth factor-beta1 (TGF-beta) compared to ACEI in
      patients with the I/I genotype but not in patients with the D/I+D/D genotype.
      DeltaATII and DeltaTGF-beta have a negative correlation with the I/I genotype and
      a positive correlation with the D/I+D/D genotypes. These correlation coefficients
      are significantly different. We suggest that in I/I patients, TGF-beta was
      reduced by ARB via effects on (ATII) type 2 receptors (AT2). In our experiments,
      the effect of ARB on TGF-beta reduction was only detected by segregation of ACE
      genotypes. This indicates that the selection of medicine in light of a patient's
      genotype is important in treating diabetic nephropathy.

PMID- 16290124
TI  - Safety and efficacy of AAV-mediated calpain 3 gene transfer in a mouse model of
      limb-girdle muscular dystrophy type 2A.
AB  - Calpainopathy (limb-girdle muscular dystrophy type 2A, LGMD2A) is a recessive
      muscular disorder caused by deficiency in the calcium-dependent cysteine protease
      calpain 3. To date, no treatment exists for this disease. We evaluated the
      potential of recombinant adeno-associated virus (rAAV) vectors for gene therapy
      in a murine model for LGMD2A. To drive the expression of calpain 3, we used
      rAAV2/1 pseudotyped vectors and muscle-specific promoters to avoid calpain 3 cell
      toxicity. We report efficient and stable transgene expression in muscle with
      restoration of the proteolytic activity and without evident toxicity. In
      addition, calpain 3 was correctly targeted to the sarcomere. Moreover, its
      presence resulted in improvement of the histological features and in therapeutic
      efficacy at the physiological levels, including correction of atrophy and full
      rescue of the contractile force deficits. Our results establish the feasibility
      of AAV-mediated calpain 3 gene transfer as a therapeutic approach.

PMID- 16290125
TI  - Versatile bioelectronic interfaces based on heterotrifunctional linking
      molecules.
AB  - Bioelectronic interfaces that allow dehydrogenase enzymes to communicate with
      electrodes have potential applications such as biosensors and biocatalytic
      reactors. A major challenge in creation of such bioelectronic interfaces is to
      orient the enzyme, its cofactor, and an electron mediator properly with respect
      to the electrode in order to achieve efficient, multistep electron transfer. This
      paper describes a versatile, new method that uses cysteine, an inexpensive,
      branched amino acid having sulfhydryl, amino, and carboxyl functional groups, to
      achieve such orientation. This approach provides greater flexibility in
      assembling complex bioelectronic interfaces than previously reported approaches
      that bind the enzyme, cofactor, and mediator in a linear chain. Cysteine was
      attached to a gold electrode through the sulfhydryl groups, to the electron
      mediator toluidine blue O (TBO) through the carboxyl group, and to the cofactor
      (e.g., NAD(P)+) through the amino group. Cyclic voltammetry, impedance
      spectroscopy, chronoamperometry and quartz crystal microbalance gravimetry were
      used to demonstrate the sequential assembly steps and the electrical activity of
      the resulting bioelectronic interface.

PMID- 16290126
TI  - Clinical evaluation of micro-scale chip-based PCR system for rapid detection of
      hepatitis B virus.
AB  - The polymerase chain reaction (PCR) is widely used to amplify a small amount of
      DNA in samples for genetic analysis. Rapid and accurate amplification is
      prerequisite for broad applications including molecular diagnostics of diseases,
      food safety, and biological warfare tests. We have developed a rapid real-time
      micro-scale chip-based PCR system, which consists of six individual thermal
      cycling modules capable of independent control of PCR protocols. The PCR volume
      is 1 microl and it takes less than 20 min to complete 40 thermal cycles. To test
      utility of a chip-based PCR system as a molecular diagnostic device, we have
      conducted the first large-scale clinical evaluation study. Three independent
      clinical evaluation studies (n = 563) for screening the hepatitis B virus (HBV)
      infection, the most popular social epidemic disease in Asia, showed an excellent
      sensitivity, e.g. 94%, and specificity, e.g. 93%, demonstrating micro-scale chip
      based PCR can be applied in molecular diagnostics.

PMID- 16290127
TI  - Does "the injury poverty trap" exist? A longitudinal study in Bavi, Vietnam.
AB  - In this study we concentrate on injuries and affected households' capacities to
      earn incomes. A longitudinal study was performed in Bavi district, Vietnam, with
      the specific objectives to investigate: (1) the affects of injuries on incomes by
      comparing income changes in injured and non-injured individuals; (2) the affect
      of injuries on social mobility by estimating households' relative risk of
      dropping into poverty for households with and without injuries and estimating the
      relative risk of escaping from poverty for households without and with injuries.
      The propensity score matching method using a logit model was used for data
      analysis. The results show that on average, the loss per household is estimated
      at VND 1,084,000 (USD 72) for poor and VND 2,598,000 (USD 173) for non-poor,
      equivalent to 11 (9) and 15 (13) working months of an average person in the poor
      and non-poor group, respectively, during 1999 (2001). The relative risk of
      dropping into poverty for non-poor households with and without injuries equal to
      1.21 (p=0.08) and the relative risk of escaping from poverty between poor
      households without and with injuries equal to 0.96 (p=0.39). In conclusion, it
      has been argued that the introduction of user fees created a poverty trap and
      thus their removal may be a solution. However, user fees are only a part of the
      burden on households. Loss of income during the illness period is likely to be a
      problem of the same magnitude. A successful solution must thus follow two tracks:
      prepayment of health care and some insurance based compensation of income losses
      during the illness period. Both reforms, if they are persistent, must be done
      within the resource limits of the local society. If the risk of catastrophic
      illness is more evenly spread across the society, it would increase the general
      welfare even if no more resources are provided.

PMID- 16290128
TI  - Communities' views on prerequisites for collaboration between modern and
      traditional health sectors in relation to STI/HIV/AIDS care in Zambia.
AB  - Traditional, complementary and alternative medicine (TM/CAM) is globally
      increasing in popularity. The World Health Organization (WHO) has advocated for
      the integration of TM/CAM in national public health policies to enhance health
      care resources. Interest in collaboration between traditional and biomedical
      health sectors has been renewed in attempts to strengthen control of the AIDS
      epidemic. However, studies exploring communities' views on the prerequisites for
      such collaboration are inexistent. We conducted 21 focus group discussions with
      community members in two Zambian urban centres (Ndola and Kabwe) to explore their
      perspectives on preconditions for useful collaboration between traditional and
      modern health workers in the management of STIs and HIV/AIDS. This study shows
      that laypersons' perspectives can be rich and inform complex policy issues. Five
      categories indicating key areas of actions were identified, including protection
      of traditional medicine and of compensation of healers, education of both groups
      of providers and adequate community involvement. The respect for some degree of
      secrecy in traditional medicine was also called for. As part of efforts to
      strengthen available resources for better care of STI/HIV/AIDS, this study
      provides policymakers, researchers and practitioners with an outline of
      fundamentals in terms of needed crucial changes at health policy level, among
      providers and in the community for sustainable collaboration between modern and
      traditional health practitioners.

PMID- 16290129
TI  - Socioeconomic determinants of regional differences in outpatient antibiotic
      consumption: evidence from Switzerland.
AB  - This paper investigates the determinants of regional variations in outpatient
      antibiotic consumption using Swiss data. The analysis contributes to the debate
      on appropriate antibiotic use by improving the understanding of its determinants,
      and may help to define more effective health care policies to reduce the
      resistance phenomenon. Findings suggest that Switzerland exhibits relatively low
      levels of consumption among European countries. There are significant differences
      between cantons both in the per capita antibiotic sales and defined daily doses
      per 1000 inhabitants (DID). Econometric estimations suggest that DID are
      significantly related to per capita income, antibiotic price, the density of
      medical practices, demographic, cultural and educational factors. The incidence
      of bacterial infections is also relevant. Appropriate policies affecting
      antibiotic consumption in the community can be designed by looking at crucial
      determinants in the model and their related impact.

PMID- 16290130
TI  - Myocardial stiffness and the timing difference between tissue Doppler imaging Ea
      and peak mitral valve opening can distinguish physiological hypertrophy in
      athletes from hypertrophic cardiomyopathy.
AB  - AIM: To differentiate between physiological and pathological left ventricular
      hypertrophy in athletes using echocardiography. METHODS AND RESULTS: Eleven
      patients with mild hypertrophic cardiomyopathy were compared against 17
      international rowers with mild left ventricular hypertrophy, and 30 age matched
      controls. The time difference between peak Ea (Doppler tissue imaging) and peak
      mitral valve opening (using M-mode) was measured simultaneously. A novel index
      (E/Ea)/LVEDD, as a measure of left ventricular stiffness was recorded. In
      athletes the peak Ea preceded peak mitral opening by: median (interquartile
      range) 20 ms (10,20), control group 15 ms (0,30), compared with HCM where Ea
      followed peak mitral opening by 10 ms (0,20), P<0.0001. In athletes the index of
      left ventricular stiffness was lower than controls 1.2 (0.93,1.4) versus 1.5
      (1.3,1.6), and HCM 2.2 (2.0,2.3), P<0.0001. CONCLUSION: Physiological hypertrophy
      can be differentiated from hypertrophic cardiomyopathy in athletes using the Ea
      peak mitral opening difference, and our index of ventricular stiffness.

PMID- 16290132
TI  - Parachute tricuspid valve.
AB  - Parachute abnormality of mitral valve frequently occurs with left sided
      obstructive lesions though occasionally may occur as an isolated lesion. Symptoms
      depend upon the severity of stenosis and associated lesions. Parachute
      abnormality of the tricuspid valve has rarely been reported and its association
      with left to right shunts has not been described so far.

PMID- 16290131
TI  - Significant improvement of myocardial function following cardiac support device
      implantation: illustration by two-dimensional strain.
AB  - Cardiac support devices (CSD) offer a new therapeutic alternative to patients
      with end-stage refractory heart failure and severe left ventricle (LV)
      dilatation. Passive mechanical constraint has been shown to reduce LV dilatation
      as well as to improve LV function and patient symptoms. Using a new
      echocardiographic technique to evaluate myocardial strain from bidimensional
      acquisitions, we describe the case of a patient with significant improvement in
      global and regional LV functions, as well as LV dyssynchrony following CSD
      implantation.

PMID- 16290133
TI  - Is the hypoxia-inducible factor pathway important in gastric cancer?
AB  - Tumour hypoxia is well recognised in oncology to be a key factor resulting in
      treatment resistance and poor prognosis. Hypoxia leads to the expression of a
      number of gene products that are involved in tumour progression, invasion and
      metastasis formation. The most important of these proteins is thought to be
      hypoxia-inducible factor-1alpha (HIF-1alpha), which appears to be a master
      regulator of the cellular response to hypoxia. HIF-1alpha expression is
      associated with a poor prognosis and treatment response in a number of tumour
      sites. There is some evidence that the HIF-1alpha pathway might be involved in
      gastric carcinogenesis. Studies have shown reactive oxygen species from
      Helicobacter pylori, associated with the development of gastric cancer, stabilise
      HIF-1alpha. Non-steroidal anti-inflammatory drugs, shown to reduce the risk of
      gastric cancer, can decrease HIF-1alpha expression. Although a large study
      correlating HIF-1alpha expression with prognosis is lacking in gastric cancer,
      the immunohistochemical expression of HIF-1alpha target genes (Glut-1, VEGF, CA9,
      iNOS) is associated with a poor prognosis. In addition, the targeted inhibition
      of HIF-1alpha has been shown to inhibit the growth of gastric tumours in animals.
      Increased understanding of the importance of hypoxia and the HIF-1alpha pathways
      may therefore hold the key to prevention strategies, improved selection of
      patients for adjuvant therapy and new treatments for the disease.

PMID- 16290135
TI  - Rapid evolution of noncoding RNAs: lack of conservation does not mean lack of
      function.
AB  - The mammalian transcriptome contains many non-protein-coding RNAs (ncRNAs), but
      most of these are of unclear significance and lack strong sequence conservation,
      prompting suggestions that they might be non-functional. However, certain long
      functional ncRNAs such as Air and Xist are also poorly conserved. In this
      article, we systematically analyzed the conservation of several groups of
      functional ncRNAs, including miRNAs, snoRNAs and longer ncRNAs whose function has
      been either documented or confidently predicted. As expected, miRNAs and snoRNAs
      were highly conserved. By contrast, the longer functional non-micro, non-sno
      ncRNAs were much less conserved with many displaying rapid sequence evolution.
      Our findings suggest that longer ncRNAs are under the influence of different
      evolutionary constraints and that the lack of conservation displayed by the
      thousands of candidate ncRNAs does not necessarily signify an absence of
      function.

PMID- 16290134
TI  - Periosteal osteosarcoma--a European review of outcome.
AB  - Periosteal osteosarcoma is a rare primary malignant bone tumour. Treatment is by
      surgical excision, but controversy remains about the value of chemotherapy. The
      members of the European Musculo Skeletal Oncology Society (EMSOS) collaborated to
      produce a dataset of 119 patients. The predominant site for the tumour was the
      femur, followed by the tibia. All but 2 patients underwent surgery, with 9
      requiring amputation and the others having limb salvage. A total of 81 patients
      had chemotherapy, of whom 50 had neoadjuvant chemotherapy. There was no standard
      chemotherapy regime, but all patients receiving chemotherapy were given
      doxorubicin combined with at least one other agent. The overall survival was 89%
      at 5 years and 83% at 10 years. Eight patients developed local recurrence, of
      whom 5 died. Survival was related to appearance of local recurrence (P < 0.0001)
      but no other single factor. The use of chemotherapy was not shown to be a
      prognostic factor, but was used in two-thirds of the patients in this study.

PMID- 16290136
TI  - Defining a genomic radius for long-range enhancer action: duplicated conserved
      non-coding elements hold the key.
AB  - Many conserved non-coding elements (CNEs) in vertebrate genomes have been shown
      to function as tissue-specific enhancers. However, the target genes of most CNEs
      are unknown. Here we show that the target genes of duplicated CNEs can be
      predicted by considering their neighbouring paralogous genes. This enables us to
      provide the first systematic estimate of the genomic range for distal cis
      regulatory interactions in the human genome: half of CNEs are >250 kb away from
      their associated gene.

PMID- 16290137
TI  - Free radical equilibrium in interscapular brown adipose tissue: relationship
      between metabolic profile and antioxidative defense.
AB  - Interscapular brown adipose tissue (IBAT) hyperplasia involves a new metabolic
      and structural profile, resulting from acclimation of animals to a cold
      environment. Cold-induced changes of several antioxidative defense (AD)
      components in IBAT and their interrelationship with uncoupling protein 1 (UCP1),
      sympathetic innervation and apoptosis were studied using cold-acclimated adult
      rat males (4 +/- 1 degrees C, 45 days). Their age-matches were maintained at 22
      +/- 1 degrees C serving as the controls. In cold-adapted rats, activities of CuZn
      and Mn-superoxide dismutase (SOD) and apoptosis were reduced, while catalase
      (CAT), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST)
      activities and glutathione (GSH) content were increased compared to the control.
      IBAT mass, protein content, plasma free fatty acid (FFA) concentration,
      sympathetic innervation and UCP1 level were significantly increased in cold
      acclimated group compared to the corresponding control. These results suggest
      that decreased CuZn and MnSOD activities in IBAT represent an adaptive response
      due to UCP1-induced mitochondrial uncoupling. Additionally, intensive fatty acid
      oxidation led to an increased H(2)O(2) production which resulted in increased
      CAT, GSH-Px and GST activities and GSH level. Generally speaking, cold-induced
      changes of AD in the IBAT are closely connected with newly established metabolic
      profile in this tissue, thus making an important part of the entire tissue
      homeostasis including cell survival.

PMID- 16290138
TI  - Evaluation of some biological parameters of Opuntia ficus indica. 2. Influence of
      seed supplemented diet on rats.
AB  - The present research was undertaken to evaluate some biological parameters in
      rats fed with a supplemented diet with Opuntia ficus indica powder seeds. Feed
      intake and body weight of rats were measured every two days during nine weeks of
      treatment. Digestibility, feed conversion efficiency and protein efficiency ratio
      were determined. No difference in digestibility was noticed between the different
      diets. The results indicated a significant decrease in body weight of rats
      receiving a diet partially substituted with O. ficus indica powder seeds,
      probably due to a significant decrease in serum-free thyroxin (FT(4)) compared to
      the control group. In the treated group, a decrease of glucose concentration in
      blood and an increase of glycogen in liver and skeletal muscle were noticed. A
      significant increase in HDL-cholesterol was noted in the group receiving the
      supplemented diet with O. ficus indica powder seeds. These results suggest that
      O. ficus indica seeds can be used as a healthy food.

PMID- 16290140
TI  - Identification of Darmstoff analogs as selective agonists and antagonists of
      lysophosphatidic acid receptors.
AB  - Darmstoff describes a family of gut smooth muscle-stimulating acetal phosphatidic
      acids initially isolated and characterized from the bath fluid of stimulated gut
      over 50 years ago. Despite similar structural and biological profiles, Darmstoff
      analogs have not previously been examined as potential LPA mimetics. Here, we
      report a facile method for the synthesis of potassium salts of Darmstoff analogs.
      To understand the effect of stereochemistry on lysophosphatidic acid mimetic
      activity, synthesis of optically pure stereoisomers of selected Darmstoff analogs
      was achieved starting with chiral methyl glycerates. Each Darmstoff analog was
      evaluated for subtype-specific LPA receptor agonist/antagonist activity,
      PPARgamma activation, and autotaxin inhibition. From this study we identified
      compound 12 as a pan-antagonist and several pan-agonists for the LPA(1-3)
      receptors. Introduction of an aromatic ring in the lipid chain such as analog 22
      produced a subtype-specific LPA(3) agonist with an EC(50) of 692 nM.
      Interestingly, regardless of their LPA(1/2/3) ligand properties all of the
      Darmstoff analogs tested activated PPARgamma. However, these compounds are weak
      inhibitors of autotaxin. The results indicate that Darmstoff analogs constitute a
      novel class of lysophosphatidic acid mimetics.

PMID- 16290139
TI  - Two estrogen replacement therapies differentially regulate expression of estrogen
      receptors alpha and beta in the hippocampus and cortex of ovariectomized rat.
AB  - As estrogens have been implicated in altered cognitive function associated with
      menopause, the purpose of the present study was to determine the regulatory
      effects of different estrogen preparations on the expression of estrogen receptor
      subtypes in the hippocampus and cortex of ovariectomized rats. The expression of
      estrogen receptor mRNA and protein was determined with RT-PCR and
      immunohistochemistry, respectively. Two estrogen reagents, Premarin and
      Progynova, were used in the present study. Premarin, a conjugated equine
      estrogen, down-regulated ER alpha expression in the hippocampus and cortex of
      ovariectomized rats and had no effect on levels of ER beta expression in the same
      two regions. However, Progynova (valerate estradiol) was shown to up-regulate ER
      beta expression in the hippocampus and cortex and had no effect on the levels of
      ER alpha expression. Our present data suggest that different estrogen reagents
      used in estrogen replacement therapy could have different regulatory effects on
      the expression of estrogen receptor subtypes, which might, at least in part,
      explain why clinically, different estrogen preparations have distinct estrogenic
      effects on target organs.

PMID- 16290141
TI  - Synthesis and SAR of highly potent and selective dopamine D(3)-receptor
      antagonists: 1H-pyrimidin-2-one derivatives.
AB  - The synthesis and SAR of novel highly potent and selective dopamine D(3)-receptor
      antagonists based on a 1H-pyrimidin-2-one scaffold are described. A-690344
      antagonized PD 128907-induced huddling deficits in rat (ED(50) 6.1mg/kg po), a
      social interaction paradigm.

PMID- 16290142
TI  - Design of novel hexahydropyrazinoquinolines as potent and selective dopamine D3
      receptor ligands with improved solubility.
AB  - We have recently reported hexahydropyrazinoquinolines as a new class of dopamine
      3 (D(3)) receptor ligands with high-affinity to the D(3) receptor and excellent
      selectivity over the closely related D(1)-like and D(2)-like receptors. However,
      our previously reported most potent and selective D(3) ligands have poor aqueous
      solubility, which greatly hinders our in vivo studies aimed at evaluation of
      their therapeutic potential in animal models. In this study, we wish to report
      the design, synthesis, and evaluation of a series of new
      hexahydropyrazinoquinolines as D(3) ligands with improved solubility. Among them,
      compound 4g has a K(i) value of 9.7 nM for the D(3) receptor and displays a
      selectivity of >5000 and 466 times over the D(1)-like and D(2)-like receptors,
      respectively. Importantly, the hydrochloride salt form of compound 4g has a good
      aqueous solubility (>50 mg/mL) and represents a promising D(3) ligand for further
      in vivo evaluations of its therapeutic potential for the treatment of drug abuse,
      restless legs syndrome, schizophrenia, Parkinson's disease, and depression.

PMID- 16290143
TI  - Cyclic urea derivatives as potent NK1 selective antagonists. Part II: Effects of
      fluoro and benzylic methyl substitutions.
AB  - A series of novel five-membered urea derivatives as potent NK1 receptor
      antagonists is described. The effects of substitution of a 4-fluoro group at the
      phenyl ring and the introduction of an alpha-methyl group at the benzylic
      position to improve potency and duration of in vivo activity are discussed.
      Several compounds with high affinity and sustained in vivo activity were
      identified.

PMID- 16290144
TI  - Pyridazines part 41: synthesis, antiplatelet activity and SAR of 2,4,6
      substituted 5-(3-oxo-3-phenylprop-1-en-1-yl)- or 5-(3-phenylprop-2
      enoyl)pyridazin-3(2H)-ones.
AB  - As part of the optimization process of the lead compound I a focussed library of
      diversely substituted pyridazin-3(2H)-ones containing a 3-oxo-3-phenylprop-1-en-1
      yl or 3-phenylprop-2-enoyl fragment at position 5 has been obtained and evaluated
      as antiplatelet agents. The structural modification at positions 2, 6 and 4 of
      the heterocyclic moiety allowed us to obtain preliminary information on the
      structure-activity relationship in this family.

PMID- 16290145
TI  - Inhibition of GABA shunt enzymes' activity by 4-hydroxybenzaldehyde derivatives.
AB  - 4-Hydroxybenzaldehyde (HBA) derivatives were examined as inhibitors for GABA
      transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH).
      Investigation of structure-activity relation revealed that a carbonyl group or an
      amino group as well as a hydroxy group at the para position of the benzene ring
      are important for both enzymes' inhibition. HBA was shown to give competitive
      inhibition of GABA-T with respect to alpha-ketoglutarate and competitive
      inhibition of SSADH. 4-Hydroxybenzylamine (HBM) also showed the competitive
      inhibition on GABA-T with respect to GABA. In conclusion, the inhibitory effects
      of HBA and HBM on both enzymes could result from the similarity between both
      molecules and the two enzymes' substrates in structure, as well as the
      conjugative effect of the benzene ring. This suggested that the presence of the
      benzene ring may be accepted by the active site of both enzymes, HBA and HBM may
      be considered as lead compounds to design novel GABA-T inhibitors.

PMID- 16290146
TI  - Carbonic anhydrase inhibitors: Valdecoxib binds to a different active site region
      of the human isoform II as compared to the structurally related cyclooxygenase II
      "selective" inhibitor celecoxib.
AB  - The high resolution X-ray crystal structure of the adduct of human carbonic
      anhydrase (CA, EC 4.2.1.1) isoform II (hCA II) with the clinically used
      painkiller valdecoxib, acting as a potent CA II and cyclooxygenase-2 (COX-2)
      inhibitor, is reported. The ionized sulfonamide moiety of valdecoxib is
      coordinated to the catalytic Zn(II) ion with a tetrahedral geometry. The phenyl
      isoxazole moiety of the inhibitor fills the active site channel and interacts
      with the side chains of Gln92, Val121, Leu198, Thr200, and Pro202. Its 3-phenyl
      group is located into a hydrophobic pocket, simultaneously establishing van der
      Waals interactions with the aliphatic side chain of various hydrophobic residues
      (Val135, Ile91, Val121, Leu198, and Leu141) and a strong offset face-to-face
      stacking interaction with the aromatic ring of Phe131 (the chi1 angle of which is
      rotated about 90 degrees with respect to what was observed in the structure of
      the native enzyme and those of other sulfonamide complexes). Celecoxib, a
      structurally related COX-2 inhibitor for which the X-ray crystal structure was
      reported earlier, binds in a completely different manner to hCA II as compared to
      valdecoxib. Celecoxib completely fills the entire CA II active site, with its
      trifluoromethyl group in the hydrophobic part of the active site and the p-tolyl
      moiety in the hydrophilic one, not establishing any interaction with Phe131. In
      contrast to celecoxib, valdecoxib was rotated about 90 degrees around the
      chemical bond connecting the benzensulfonamide and the substituted isoxazole ring
      allowing for these multiple favorable interactions. These different binding modes
      allow for the further drug design of various CA inhibitors belonging to the
      benzenesulfonamide class.

PMID- 16290147
TI  - Inhibiting protein-amyloid interactions with small molecules: a surface chemistry
      approach.
AB  - This paper presents a surface-based approach to inhibit the binding of proteins
      to Alzheimer's-related beta-amyloid (Abeta) fibrils with small molecules. It
      reports the idea of using an intracellular, disease-related fibril as a material
      whose surface can be coated with small molecules. Using an ELISA-based assay,
      molecular surface coatings with thioflavin T are shown to inhibit 65+/-10% of the
      binding of two different anti-Abeta IgGs to Abeta fibrils. A molecular surface
      coating with 3,6-diamino acridine was able to inhibit 76+/-10% of the binding of
      an anti-Abeta IgG to Abeta fibrils. Maximal inhibition of these protein-amyloid
      interactions appears in the low to mid-micromolar range of small molecule. This
      demonstration that molecular surface coatings can be used to attenuate the
      interaction of proteins with these fibrils suggests a potentially new strategy
      for therapeutics in neurodegenerative amyloid diseases.

PMID- 16290148
TI  - 3-Amino-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: a new class of CDK2
      inhibitors.
AB  - We have recently reported about a new class of Aurora-A inhibitors based on a
      bicyclic tetrahydropyrrolo[3,4-c]pyrazole scaffold. Here we describe the
      synthesis and early expansion of CDK2/cyclin A-E inhibitors belonging to the same
      chemical class. Synthesis of the compounds was accomplished using a solution
      phase protocol amenable to rapid parallel expansion. Compounds with nanomolar
      activity in the biochemical assay and able to efficiently inhibit CDK2-mediated
      tumor cell proliferation have been obtained.

PMID- 16290149
TI  - Development of chemically stable solid phases for the target isolation with
      reduced nonspecific binding proteins.
AB  - Poly(methacrylate) matrices for affinity resins were designed and synthesized
      based on our previous results that nonspecific protein absorption on affinity
      resins strongly depended on their hydrophobic property. The novel affinity resins
      bearing FK506 (6a, 6b) captured specific binding protein, FKBP12, with a small
      amount of nonspecific binding proteins. The amount of nonspecific binding
      proteins on 6a-6b was much reduced compared to that on commercially available
      poly(methacrylate) resins, Toyopearl (8), and was almost the same as that on one
      of the most popular resins, Affigel (9). Interestingly, 6a and 6b could isolate
      FKBP52 as a specific binding protein as well, although 8 and 9 could not.

PMID- 16290150
TI  - Platelet mitochondrial evaluation during cytochrome c and dichloroacetate
      treatments of MELAS.
AB  - We hypothesized that serial changes in platelet (PLT) mitochondrial enzyme (ME)
      activities might correspond to the effects of medications for mitochondrial
      encephalomyopathy and stroke-like episodes (MELAS). Cytochrome c and sodium
      dichloroacetate (DCA) were given to a 7-year-old girl with MELAS who had an
      A3243G mitochondrial DNA mutation. The effects were evaluated with whole PLT-ME
      assays, developed by our group, using a microplate-reader. During cytochrome c
      treatment, complex II+III (II+III), complex IV (IV) and citrate synthase (CS)
      activities showed gradual but statistically significant decrease. II+III activity
      dropped below normal. II+III/CS activity was initially below normal, followed by
      a transient improvement, then decreased again before the appearance of central
      nervous system symptoms. II+III, IV, II+III/CS and IV/CS activities reached their
      lowest levels in association with a stroke-like episode, then increased with DCA
      treatment. Our results suggest that progressive mitochondrial dysfunction may
      occur before the stroke-like episodes in MELAS and that DCA treatment may
      increase mitochondrial activities. Our whole PLT-ME assay system may be useful
      for serially evaluating mitochondrial functions in relation to clinical symptoms.

PMID- 16290151
TI  - The UK Stem Cell Bank: its role as a public research resource centre providing
      access to well-characterised seed stocks of human stem cell lines.
AB  - The rapidly expanding field of stem cell research offers the potential to develop
      therapeutic agents to treat diseases such as Parkinson's, diabetes and heart
      disease. It is important that stem cell lines derived from quality-controlled and
      well-characterised cell banks should be made available to both the scientific and
      clinical communities to promote high-quality research and development. The
      requirement in the United Kingdom (UK) for rigorous regulation of the procurement
      and use of embryonic stem (ES) cell lines led the UK government to fund the
      establishment of a national bank for stem cell lines. The UK Stem Cell Bank
      (UKSCB) hosted at the National Institute for Biological Standards and Control
      (NIBSC) is committed to working closely with the clinical and research
      communities to provide qualified stocks of human stem cell lines of adult, foetal
      and embryonic origin for both research use and for use in emerging human therapy.

PMID- 16290152
TI  - Nano-sized MRI contrast agents with dendrimer cores.
AB  - Gadolinium-based MRI contrast agents (CAs) can be effective at a approximately
      100-fold lower concentration of Gadolinium ions in comparison to the
      concentration of Iodine atoms required for CT imaging. Therefore, a number of
      dendrimer based macromolecular MRI CAs of various sizes and properties prepared
      employing relatively simple chemistry are readily available that can provide
      sufficient contrast enhancement for various applications. Molecules up to 20 nm
      in diameter behave differently in the body depending on their size. Even if these
      molecules possess similar chemical properties, small changes in size can greatly
      impact their pharmacokinetics. Changes in molecular size up to 15 nm in diameter
      altered permeability across the vascular wall, excretion route, and recognition
      by the reticuloendothelial system. Smaller sized polyamidoamine (PAMAM) dendrimer
      based contrast agents, i.e., less than 3 nm in diameter, easily "leak" across the
      vascular wall resulting in rapid perfusion throughout the body. Contrast agents 3
      6 nm in diameter were quickly excreted through the kidney indicating these agents
      to be potentially suitable as functional renal contrast agents. Contrast agents 7
      12 nm in diameter were retained in circulation and were better suited for use as
      blood pool contrast agents. Hydrophobic variants of CAs formed with
      polypropylenimine diaminobutane (DAB) dendrimer cores quickly accumulated in the
      liver and potentially have use as liver contrast agents. Larger hydrophilic
      agents have suitable characteristics for lymphatic imaging. Finally, contrast
      agents conjugated with either monoclonal antibodies or with avidin are able to
      function as tumor-specific contrast agents and might also be employed as either
      gadolinium neutron capture therapy or in conjunction with radioimmunotherapy.

PMID- 16290153
TI  - Pharmaceutical applications of embryonic stem cells.
AB  - Embryonic stem cells (ESCs) will become a source of all adult differentiated
      cells once reliable protocols for directed differentiation have been established.
      This resource will revolutionise laboratory cell biology and will provide much
      improved cell culture models for discovery and development of drugs, and
      fundamental studies of the genetic basis of disease. These are early days, and
      there are few examples of practical outcomes in the pharmaceutical world, though
      in recent years some drug-like molecules, which direct differentiation, have been
      discovered. At this stage the focus is on understanding the signalling systems
      and transcription factors that drive differentiation, on characterisation and
      isolation of precursor cells, and on establishing methods to improve the
      homogeneity of differentiated cells derived from ESCs. There is particular
      interest in establishing methods for deriving fully differentiated human cells
      from human ESCs (HESCs), but there are challenges to be met before HESC
      technology can be taken up in a widespread manner. Protocols for expansion of
      HESC cultures are labour-intensive at present. There is an urgent need for
      discovery of factors that will allow serum-free (and feeder cell-free) expansion
      of HESCs, and which can be applied to the majority of HESC lines. Our expectation
      is that adequate protocols will emerge in the coming years opening the way for
      development of many cell culture tools in the pharmaceutical industry. Here we
      review the current status and future prospects for this exciting field and
      encourage pharmaceutical scientists to play a role in directing its development.

PMID- 16290154
TI  - Amyloidosis in cystic fibrosis: a case series.
AB  - As the life expectancy of patients with cystic fibrosis increases, unusual
      complications including amyloidosis are increasingly recognised. We report three
      cases of amyloidosis including a unique case presenting with a hemorrhagic and
      thrombotic diatheisis. This complication of amyloidosis has never been reported
      in cystic fibrosis.

PMID- 16290155
TI  - HER-2 gene amplification by chromogenic in situ hybridisation (CISH) compared
      with fluorescence in situ hybridisation (FISH) in breast cancer-A study of two
      hundred cases.
AB  - The purpose of the study was to compare two methods used to analyse HER-2 gene
      amplification (fluorescence in situ hybridisation (FISH) and chromogenic in situ
      hybridisation (CISH)), and determine the accuracy of the antibodies CB11 and
      HercepTest for immunohistochemical detection of HER-2 overexpression from
      archival breast cancer tissue. Additionally, interobserver variability in the
      interpretation of CISH and immunohistochemical tests was measured. Two hundred
      cases of invasive breast carcinoma diagnosed between 2000 and 2003 were selected.
      Immunohistochemistry (IHC) was performed with HercepTest and CB11, and gene
      amplification was determined by FISH (PathVision, Vysis) and CISH (Zymed) using
      tissue macroarrays. An excellent concordance (94.8%) was found between CISH and
      FISH. Considering FISH as gold standard, sensitivity of CISH was 97.5% and
      specificity 94%. Overall interobserver agreement of CISH was 97.5% and of IHC
      84%. Both antibodies showed a sensitivity of 95.2% and a specificity of 70.7%
      (CB11) and 81.2% (HercepTest). Our results show that CISH is a highly accurate,
      reproducible and practical technique to determine HER-2 gene amplification. CB11
      and HercepTest are good screening methods with a high sensitivity. The
      performance of tissue macroarrays to test HER-2 status by IHC, FISH and CISH has
      demonstrated to be an available and effective method to study large series of
      tumours.

PMID- 16290158
TI  - Lifelong education and its relevance to nursing. 1987.

PMID- 16290159
TI  - Research in Nurse Education Today: do we meet our aims and scope? 2002.

PMID- 16290160
TI  - Analysis and sequencing of the active-site peptide from native and
      organophosphate-inactivated acetylcholinesterase by electrospray ionization,
      quadrupole/time-of-flight (QTOF) mass spectrometry.
AB  - A method to identify and sequence recombinant mouse acetylcholinesterase
      (rMoAChE) including the native and organophosphate-modified active-site peptides
      was developed using capillary liquid chromatography with electrospray ionization,
      quadrupole/time-of-flight mass spectrometry. Addition of 2-propanol to the
      reversed-phase gradient system and a decreased gradient slope improved the
      peptide resolution and the signal of the active-site peptide. The highest protein
      coverage and active-site peptide signal were achieved when the
      rMoAChE:chymotrypsin ratio of 5:1 was used with digestion at 37 degrees C.
      rMoAChE and the active-site peptide were identified and sequenced from
      chymotryptic digests of native, methyl paraoxon-, and ethyl paraoxon-inactivated
      rMoAChE showing unequivocally that the exact modification site was the active
      site serine.

PMID- 16290162
TI  - Aryl nucleoside H-phosphonates. Part 15: Synthesis, properties and, anti-HIV
      activity of aryl nucleoside 5'-alpha-hydroxyphosphonates.
AB  - Aryl nucleoside 5'-H-phosphonates 4 bearing AZT or 2',3'-dideoxyuridine moieties
      were subjected to reaction with various aromatic aldehydes to produce nucleoside
      5'-alpha-hydroxyphosphonate derivatives 2 as potential anti-HIV agents. Stability
      of the title compounds in cell culture media was investigated and three distinct
      decomposition pathways were identified. The anti-HIV activity of
      hydroxyphosphonates 2 correlates well with the type and extent of their chemical
      or enzymatic degradation in culture medium (RPMI 1640 containing 10% FBS),
      suggesting that aryl nucleoside 5'-hydroxyphosphonates 2 act as depot forms of
      the parent antiviral nucleosides.

PMID- 16290161
TI  - Synthesis and structure-activity studies of schweinfurthin B analogs: Evidence
      for the importance of a D-ring hydrogen bond donor in expression of differential
      cytotoxicity.
AB  - The synthesis and biological evaluation of several enantioenriched schweinfurthin
      B analogs were undertaken to develop structure-activity relationships and guide
      design of probes for their putative molecular target. The desired stilbenes
      contain a common left-half hexahydroxanthene ring system and an aromatic right
      half with varied substituents. The synthesis involves penultimate Horner
      Wadsworth-Emmons coupling of one of several right-half phosphonates with the
      aldehyde comprising the left-half of 3-deoxyschweinfurthin B. Preparation of the
      requisite phosphonates, and the respective stilbenes, as well as the cytotoxicity
      profiles of these new compounds in the National Cancer Institute's 60 cell-line
      anticancer screen is described. Several of these analogs displayed cytotoxicity
      patterns well-correlated with the natural product and differences in activity of
      approximately 10(3) across the various cell lines. Together, these assay results
      indicate the importance of at least one free phenol group on the aromatic D-ring
      of this system for differential cytotoxicity.

PMID- 16290163
TI  - Synthesis and biological activity of novel 4,4-difluorobenzazepine derivatives as
      non-peptide antagonists of the arginine vasopressin V1A receptor.
AB  - To find potent and selective antagonists of the arginine vasopressin (AVP) V1A
      receptor, optimization studies of compounds structurally related to (Z)-N-{4'
      [(4,4-difluoro-5-carbamoylmethylidene-2,3,4,5-tetrahydro-1H-1-benzazepin-1
      yl)carbonyl]phenyl}carboxamide were performed. The synthesis and pharmacological
      properties of these compounds are described. We first investigated the effect of
      the carboxamide moiety, and found that a 2-methylfuran-3-carbonyl group at this
      position increased V1A binding affinity and selectivity for the V1A receptor
      versus the V2 receptor. The amino group of the 5-carbamoylmethylidene moiety was
      also examined, and a 4-piperidinopiperidino group was found to be optimal at this
      position. The hemifumarate of compound 12l (YM218) was shown to exhibit potent
      binding affinity, V1A receptor selectivity, and in vivo antagonist activity.

PMID- 16290164
TI  - Synthesis of 3-deaza-3-nitro-2'-deoxyadenosine.
AB  - Photoactivable deoxyadenosine mimic, 3-deaza-3-nitro-2'-deoxyadenosine (2), was
      prepared using two different synthetic routes. The first route involved base
      catalyzed glycosylation of 3-deaza-3-nitroadenine, which was prepared by
      regioselective nitration of 3-deazaadenine. In the second route, the convertible
      nucleoside 6-O-(2,4,6-trimethylphenyl)-3-deaza-2'-deoxyadenosine (28) was used to
      introduce 6-NH2 group in the last step.

PMID- 16290165
TI  - Synthesis, SAR studies, and evaluation of 1,4-benzoxazepine derivatives as
      selective 5-HT1A receptor agonists with neuroprotective effect: Discovery of
      Piclozotan.
AB  - A new series of 1,4-benzoxazepine derivatives was designed, synthesized, and
      evaluated for binding to 5-HT1A receptor and cerebral anti-ischemic effect. A lot
      of compounds exhibited nanomolar affinity for 5-HT1A receptor with good
      selectivity over both dopamine D2 and alpha1-adrenergic receptors. Among these
      compounds, 3-chloro-4-[4-[4-(2-pyridinyl)-1,2,3,6-tetrahydropyridin-1-yl]butyl]
      1, 4-benzoxazepin-5(4H)-one (50: SUN N4057 (Piclozotan) as 2HCl salt) showed
      remarkable neuroprotective activity in a transient middle cerebral artery
      occlusion (t-MCAO) model.

PMID- 16290166
TI  - Enantiomeric N-methyl-4-piperidyl benzilates as muscarinic receptor ligands:
      Radioligand binding studies and docking studies to models of the three muscarinic
      receptors M1, M2 and M3.
AB  - Benzilic ester derivatives with a basic moiety like N-methyl-4-piperidyl
      benzilates are potential drugs for the treatment of urinary incontinence,
      duodenal and gastric ulcers and Parkinson's disease. The effect of structural
      variations of chiral N-methyl-4-piperidyl benzilates was investigated using
      radioligand binding studies on muscarinic receptors (M1-M3). The results of the
      binding studies demonstrate that the absolute configuration and the aromatic
      substituent of benzilates have an influence on muscarinic affinity and
      selectivity. In this regard, (S)-configuration of benzilates and hydrophilic
      aromatic substituents seems to enhance muscarinic affinity. A model of the
      receptor ligand complex for N-methyl-4-piperidyl benzilates was obtained by
      molecular modelling. Both the affinity of enantiomeric benzilic esters and the
      subtype selectivity for muscarinic receptors are comprehensively explained by
      this model.

PMID- 16290167
TI  - Ionization state of pyridoxal 5'-phosphate in D-serine dehydratase,
      dialkylglycine decarboxylase and tyrosine phenol-lyase and the influence of
      monovalent cations as inferred by 31P NMR spectroscopy.
AB  - The 31P NMR spectroscopy of three pyridoxal 5'-phosphate-dependent enzymes,
      monomeric D-serine dehydratase, tetrameric dialkylglycine decarboxylase and
      tetrameric tyrosine phenol-lyase, whose enzymatic activities are dependent on
      alkali metal ions, was studied. 31P NMR spectra of the latter two enzymes have
      never been reported, their 3D-structures, however, are available. The cofactor
      phosphate chemical shift of all three enzymes changes by approximately 3 ppm as a
      function of pH, indicating that the phosphate group changes from being
      monoanionic at low pH to dianionic at high pH. The 31P NMR signal of the
      phosphate group of pyridoxal 5'-phosphate provides a measure of the active site
      changes that occur when various alkali metal ions are bound. Structural
      information is used to assist in the interpretation of the chemical shift changes
      observed. For D-serine dehydratase, no structural data are available but
      nevertheless the metal ion arrangement in the PLP binding site can be predicted
      from 31P NMR data.

PMID- 16290168
TI  - SVM-BALSA: remote homology detection based on Bayesian sequence alignment.
AB  - Biopolymer sequence comparison to identify evolutionarily related proteins, or
      homologs, is one of the most common tasks in bioinformatics. Support vector
      machines (SVMs) represent a new approach to the problem in which statistical
      learning theory is employed to classify proteins into families, thus identifying
      homologous relationships. Current SVM approaches have been shown to outperform
      iterative profile methods, such as PSI-BLAST, for protein homology
      classification. In this study, we demonstrate that the utilization of a Bayesian
      alignment score, which accounts for the uncertainty of all possible alignments,
      in the SVM construction improves sensitivity compared to the traditional dynamic
      programming implementation over a benchmark dataset consisting of 54 unique
      protein families. The SVM-BALSA algorithms returns a higher area under the
      receiver operating characteristic (ROC) curves for 37 of the 54 families and
      achieves an improved overall performance curve at a significance level of 0.07.

PMID- 16290169
TI  - Ab initio fragment molecular orbital (FMO) method applied to analysis of the
      ligand-protein interaction in a pheromone-binding protein.
AB  - Full quantum computation of the electronic state of proteins has recently become
      possible by the advent of the ab initio fragment molecular orbital (FMO) method.
      We applied this method to the analysis of the interaction between the Bombyx mori
      pheromone-binding protein and its ligand, bombykol. The protein-ligand
      interaction of this molecular complex was minutely analyzed by the FMO method,
      and the analysis revealed several important interactions between the ligand and
      amino acid residues.

PMID- 16290170
TI  - Synthesis and evaluation of a technetium-99m-labeled
      diethylenetriaminepentaacetate-deoxyglucose complex ([99mTc]-DTPA-DG) as a
      potential imaging modality for tumors.
AB  - This study describes the radiolabeling and preliminary biologic testing of
      diethylenetriaminepentaacetic acid (DTPA)-deoxyglucose (DG) labeled with (99m)Tc.
      A one-step [(99m)Tc]-DTPA-DG kit was prepared using the stannous chloride
      reduction method. When (99m)TcO(4)(-) was added to the DTPA-DG kit at room
      temperature the radiochemical purity 30 min later was 99.2%, and it remained
      >98.6% for 6 h. Rapid blood clearance of [(99m)Tc]-DTPA-DG was observed in in
      vivo biodistribution, the main route of clearance was via the kidneys. No
      significant accumulation in any other organs was seen. The tumor-to-brain and
      tumor-to-muscle concentration ratios for [(99m)Tc]-DTPA-DG uptake were higher
      than those for fluorine-18-flurodeoxyglucose ((18)F-FDG). Scintigraphic results
      demonstrated the feasibility of [(99m)Tc]-DTPA-DG imaging tumors. The [(99m)Tc]
      DTPA-DG complex is a potential imaging agent due to the ideal physical
      characteristics of the radionuclide, ease of preparation, low cost, early
      accumulation and the preference for the renal route of excretion.

PMID- 16290171
TI  - The historical delivery of antibiotics from microbial natural products--can
      history repeat?
AB  - Microbial natural products are the origin of most of the antibiotics on the
      market today. However, research in antibiotics and natural products has declined
      significantly during the last decade as a consequence of diverse factors, among
      which the lack of interest of industry in the field and the strong competition
      from collections of synthetic compounds as source of drug leads. As a
      consequence, there is an alarming scarcity of new antibiotic classes in the
      pipelines of the pharmaceutical industry. Still, microbial natural products
      remain the most promising source of novel antibiotics, although new approaches
      are required to improve the efficiency of the discovery process. The impact of
      microbial biodiversity, the influence of growth conditions on the production of
      secondary metabolites, the choice of the best approach at the screening step and
      the challenges faced during the isolation and identification of the active
      compounds are examined in this review as the critical factors contributing to
      success in the effort of antibiotic discovery from microbial natural products.

PMID- 16290173
TI  - Does the cell wall of bacteria remain a viable source of targets for novel
      antibiotics?
AB  - Whether the bacterial cell wall remains a viable source of novel antibacterials
      is addressed here by reviewing screen and design strategies for discovery of
      antibacterials with a focus on their output. Inhibitors for which antibacterial
      activity has been shown to be due to specific inhibition of a reaction
      (antibacterially validated inhibitors) are known for 8 of the 14 conserved
      essential steps of the pathway. Antibacterially validated enzyme inhibitors exist
      for six of these steps. The possible obstacles to finding validated inhibitors of
      the remaining enzymes are discussed and some strategies are suggested.

PMID- 16290174
TI  - Efflux systems in bacterial pathogens: an opportunity for therapeutic
      intervention? An industry view.
AB  - The efflux systems of bacteria protect cells from antibiotics and biocides by
      actively transporting compounds out of the cytoplasm and/or periplasm and thereby
      limit their steady-state accumulation at their site(s) of action. The impact of
      efflux systems on the efficacy of antibiotics used in human medicine and animal
      husbandry is becoming increasingly apparent from the characterization of drug
      resistant strains with altered drug efflux properties. In most instances, efflux
      mediated antibiotic resistance arises from mutational events that result in their
      elevated expression and, in the case of efflux pumps with broad substrate
      specificity, can confer multi-drug resistance (MDR) to structurally unrelated
      antibiotics. Knowledge of the role of efflux systems in conferring antibiotic
      resistance has now been successfully exploited in the pharmaceutical industry and
      contributed, in part, to the development of new members of the macrolide and
      tetracycline classes of antibiotics that circumvent the efflux-based resistance
      mechanisms that have limited the clinical utility of their progenitors. The
      therapeutic utility of compounds that inhibit bacterial drug efflux pumps and
      therein potentiate the activity of a co-administered antibiotic agent remains to
      be validated in the clinical setting, but the approach holds promise for the
      future in improving the efficacy and/or extending the clinical utility of
      existing antibiotics. This review discusses the potential of further exploiting
      the knowledge of efflux-mediated antibiotic resistance in bacteria toward the
      discovery and development of new chemotherapeutic agents.

PMID- 16290175
TI  - CXC chemokines modulate IgE secretion and pulmonary inflammation in a model of
      allergic asthma.
AB  - The pathophysiology of asthma is influenced by exposure to allergens and
      endotoxin. Although the role of allergen-induced eosinophilia has been widely
      studied, neutrophil-mediated responses remain elusive. A role for neutrophils in
      the asthmatic responses is likely since human neutrophils have been shown to
      express IgE receptors, as well as receptors for many cytokines and chemokines
      implicated in the pathogenesis of asthma. In this study we investigated
      neutrophil involvement in a novel, house dust extract (HDE) induced model of
      asthma-like pulmonary inflammation. Mice were immunized and challenged with HDE
      containing high levels of cockroach allergens, 377 U/ml Bla g1 and 6249 ng/ml Bla
      g2. The biological activity of the murine chemokines KC and MIP-2 was inhibited
      with specific rabbit antisera. Differential counting of cells recovered from the
      bronchoalveolar lavage (BAL) fluid showed that neutralization of KC and MIP-2
      significantly decreased pulmonary recruitment of neutrophils (reduced 86%) and
      lymphocytes (reduced 76%). Neutralization of these chemokines also exerted a
      systemic effect with a significant decrease in plasma IgE levels, 547 ng/ml+/-65
      compared to 1314 ng/ml+/-247 for control sera treated animals. This study shows
      that CXC chemokines play an important role in allergy and asthma both at the
      level of pulmonary cell recruitment and systemic immune responses.

PMID- 16290172
TI  - Polychlorinated biphenyls induce arachidonic acid release in human platelets in a
      tamoxifen sensitive manner via activation of group IVA cytosolic phospholipase A2
      alpha.
AB  - Polychlorinated biphenyls (PCBs) are stable compounds commonly found in nature as
      environmental pollutants. PCBs can affect the endocrine function of hormones such
      as steroid-hormones. Also, PCBs are known to be inducers of arachidonic acid
      release in various cells. We report, here, the effects of PCBs on eicosanoid
      formation, arachidonic acid release and cytosolic phospholipase A2-alpha (cPLA2
      alpha) activation in human platelets. Ortho-substituted PCBs induced a time and
      dose-dependent release of arachidonic acid and the concomitant formation of 12(S)
      hydroxy-5,8-cis-10-trans-14-cis-eicosatetraenoic acid (12-HETE) and 12(S)-hydroxy
      5-cis-8,10-trans-heptadecatrienoic acid (12-HHT) in human platelets. The release
      of arachidonic acid and the formation of 12-HETE was completely blocked by the
      cPLA2-alpha inhibitors AACOCF3 or pyrrolidine-1. PCB-treatment of platelets
      demonstrated that the cPLA2-alpha protein as well as PLA2 activity translocated
      to the membrane fraction, independent of a rise in intracellular Ca2+.
      Furthermore, electrophoretic gel mobility shift analysis of cPLA2-alpha on SDS
      PAGE demonstrated a PCB-dependent phosphorylation of cPLA2-alpha. The effects of
      17beta-estradiol and two structurally unrelated anti-estrogens, nafoxidin and
      tamoxifen on PCB-induced arachidonic acid release in platelets were also
      investigated. Both nafoxidin and tamoxifen inhibited PCB-induced arachidonic acid
      release as well as 12-HETE and 12-HHT formation. Interestingly, platelets
      incubated with PCBs did not aggregate despite the fact that robust release of
      arachidonic acid was observed. In summary, these results demonstrate that certain
      PCBs induce activation of cPLA2-alpha independent of a rise in intracellular
      calcium and a robust release of arachidonic acid release with resulting
      eicosanoid formation in human platelets.

PMID- 16290176
TI  - Expression, purification, and characterization of two NADP-malic enzymes of rice
      (Oryza sativa L.) in Escherichia coli.
AB  - NADP-malic enzymes (NADP-ME) are isozymes in plants. To clarify the diversity and
      function of NADP-ME isozymes in rice, we produced two active GST-fused NADP-ME
      proteins, NADP-ME2 and NADP-ME3 in Escherichia coli, and the fusion proteins were
      purified by affinity chromatography using a glutathione-Sepharose 4B column.
      After enzymatic cleavage of the GST tag, final yields were 1.4 mg/g wet cell
      weight (wcw) for NADP-ME2 and 3.5 mg/g wcw for NADP-ME3, respectively, and the
      molecular weights of NADP-ME2 and NADP-ME3 were about 65 and 62 kDa,
      respectively. The optimum pH is 7.3 for NADP-ME2 and 7.7 for NADP-ME3. The Km
      values for malate of NADP-ME2 and NADP-ME3 were 2.6 and 3.1 mM, whereas the Km
      values for NADP were 79 and 93 microM, respectively. The Kcat values of NADP-ME2
      and NADP-ME3 for malate were about 91.7 and 96.7 s-1, respectively, and the Kcat
      values for NADP about 88.3 and 98.3 s-1, respectively. These results suggest that
      the two rice isozymes of NADP-ME in vitro have similar kinetic parameter.

PMID- 16290177
TI  - A hypopharyngeal gland protein of the worker honeybee Apis mellifera L. enhances
      proliferation of primary-cultured rat hepatocytes and suppresses apoptosis in the
      absence of serum.
AB  - The worker honeybees of Apis mellifera L. age-dependently change from nurse bees
      which take care of their brood to forager bees which collect for nectar and
      convert it into honey during their lifespan of 30-40 days. A 56-kDa protein
      (p56kP-4) was shown to be present only in the nurse-bee hypopharyngeal gland.
      Here, we investigated the physiological effects of p56kP-4 on primary-cultured
      rat hepatocytes in the absence of serum. The p56kP-4 recombinant protein
      expressed in Escherichia coli significantly stimulated hepatocyte DNA synthesis
      and protected cells from apoptosis induced by serum deprivation. It also
      activated mitogen-activated protein kinase, as well as protein kinase B, which is
      a key regulator of cell survival. These findings suggest that p56kP-4 has a
      growth factor-like action on primary-cultured rat hepatocytes.

PMID- 16290178
TI  - Structural and ultrastructural features of boar bulbourethral glands.
AB  - The morphological features of boar bulbourethral glands were examined by light
      and transmission microscopy. Bulbourethral glands are compound tubuloalveolar
      glands surrounded by a capsule of dense connective tissue and arranged in
      multiple lobules formed by endpieces and excretory ducts. Endpieces and excretory
      ducts are both lined by a single epithelium of mucous cells with a basal nucleus.
      Epithelial cells accumulate secretory granules containing neutral and
      carboxylated acid mucosubstances and a small amount of sulphated acid
      mucosubstances. The ultrastructure of epithelial cells varies according to the
      secretory cycle. In initial stages, the cells show a columnar shape and secretory
      granules unevenly distributed in the cytoplasm. As the synthesis of
      mucosubstances progresses, the amount of the secretory granules increases and the
      cellular shape becomes pyramidal. Secretory granules can contain inclusions and
      present differences among them according to their different phases of formation.
      In pyramidal cells, secretory products are released into the lumen by a merocrine
      mechanism.

PMID- 16290179
TI  - Neighborhood crime, deprivation, and preterm birth.
AB  - PURPOSE: Significant racial disparity in preterm birth (PTB; birth at <37 weeks'
      gestation) exists, poorly explained by Individual-level factors. This research
      explores whether neighborhood crime contributes to the racial disparity in PTB.
      METHODS: Geocoded Wake County, NC, birth records and crime-report data for 1999
      to 2001 were merged with US Census data (2000). Race-stratified logistic and
      multilevel logistic models produced odds ratios (ORs) and 95% confidence
      intervals (CIs) for block-group violent, theft, property, and vice crime rates
      and singleton PTB. RESULTS: A total of 13,960 women resided in a 114-block-group
      crime area. Non-Hispanic black women were more likely than non-Hispanic white
      women to deliver preterm (12.8% versus 6.7%), live in economically deprived block
      groups (42.2% versus 19.3% in the highest deprivation quartile), and experience
      more crime (32.0% versus 3.8% in the highest violent-crime-rate quartile).
      Quartiles of violent, theft, property, and vice crimes were associated with PTB
      in unadjusted models. Living in very high violent-crime-rate block-group
      quartiles was suggestive of increased odds of PTB for white and black non
      Hispanic women (OR = 1.5; 95% CI, 0.9-2.6; and OR = 1.4; 95% CI, 1.0-2.1,
      respectively) in adjusted models. Other crime effects were attenuated after
      adjustment. CONCLUSIONS: Differential neighborhood exposures may contribute to
      racial disparity in PTB.

PMID- 16290180
TI  - Statistical basis for predicting the need for bacterially induced beach closures:
      Emergence of a paradigm?
AB  - Data collected from four beaches along southern Lake Michigan (USA) during the
      summer of 2004 were subjected to correlation and time-series regression analyses
      aimed at identifying an optimal suite of variables that could be used to predict
      log Escherichia coli concentrations in real time. Although other variables
      entered into the regression equations, waves, outfalls of bacteria from an
      adjacent stream, sunshine, temperature, and time of day (morning versus
      afternoon) turned out to be the most useful and consistent predictive variables.
      A post-hoc analysis showed that regression models are much more successful than
      previous day's bacterial concentration at predicting whether or not the beach
      water quality is above or below the threshold criteria for full body contact
      established by the USEPA. Additional analyses, using 99% confidence intervals on
      predicted logE. coli concentrations, indicated that in extreme cases of high or
      low health threat, model predictions are likely to be accurate about 90% of the
      time. The findings of this study are consistent with previous work in the region
      and seem to indicate that real-time monitoring of hydrometeorological variables
      can provide the basis of an early warning system for protecting the public from
      the health risk posed by harmful pathogens in beach water.

PMID- 16290181
TI  - Zero net growth in a membrane bioreactor with complete sludge retention.
AB  - A bench-scale membrane bioreactor was operated with complete sludge retention in
      order to evaluate biological processes and biomass characteristics over the long
      term. The investigation was carried out by feeding a bench-scale plant with real
      sewage under constant volumetric loading rate (VLR = 1.2 gCOD L(react)(-1) h(
      1)). Biological processes were monitored by measuring substrate removal
      efficiencies and biomass-related parameters. The latter included bacterial
      activity as determined through respirometric tests specifically aimed at
      investigating long term heterotrophic and nitrifying activity. After about 180
      days under the imposed operating conditions, the system reached equilibrium
      conditions with constant VSS concentration of 16-18gL(-1), organic loading rate
      (OLR) below 0.1 gCOD gVSS(-1) d(-1) and specific respiration rates of 2-3 mgO2
      gVSS(-1) h(-1). These conditions were maintained for more than 150 days,
      confirming that an equilibrium had been achieved between biomass growth,
      endogenous metabolism, and solubilization of inorganic materials.

PMID- 16290183
TI  - Filtration methods for recovery of Bacillus anthracis spores spiked into source
      and finished water.
AB  - Spores of Bacillus anthracis Sterne strain were recovered from 100ml and 1L
      volumes of tap and source waters using filtration through a 0.45um filter,
      followed by overnight culture on agar plates. In a set of experiments comparing
      sheep red blood cell (SRBC) plates with a chromogenic agar formulation designed
      by R & F Laboratories, with a spiking dose of 47 plate-enumerated spores in 100
      ml tap water, the mean spore recoveries were 34.0 and 30.8 spores, respectively.
      When a spiking dose of 100 fluorescence activated cell sorter(FACS)-enumerated
      spores was used in 100 ml potable water, the average recovery with SRBC plates
      was 48 spores. Detection efforts with spiking doses of 35 and 10 spores in 1 L
      tap water were successful, but recovery efforts from spiked 1 L volumes of source
      water were problematic due to the concomitant growth of normal spore-forming
      flora. Recoveries were also attempted on 10 L volumes of tap water. For a spiking
      dose of 100 spores, mean recovery from six replicates was 11 spores (+/- 6.8,
      range 2-20), and for a spiking dose of 10 spores, mean recovery from six
      replicates was 2.3 spores (+/- 3.5, range 0-9). Efforts were also made to "direct
      detect" spores via polymerase chain reaction (PCR) on washes from filters. When
      spiking 534 spores in 100 ml, 9/9 replicates of spiked tap water, 6/6 source
      water replicates, and 0/3 unspiked controls were positive by lef PCR. When 534
      spores were spiked into 1 L tap water, the lef PCR was unsuccessful; however,
      using the nested vrrA PCR resulted in 4/9 spiked samples, and 0/3 unspiked
      controls, testing positive. Our results indicate that an inexpensive and user
      friendly method, utilizing filtration apparatus commonly present in many water
      quality testing labs, can readily be adapted for use in detecting this potential
      threat agent.

PMID- 16290182
TI  - Removal of neutral chloroacetamide herbicide degradates during simulated unit
      processes for drinking water treatment.
AB  - Four chloroacetamide herbicides and 20 neutral chloroacetamide derivatives (known
      to occur as their environmental degradates) were subjected to simulated drinking
      water treatment (coagulation, oxidation and adsorption). Coagulation with alum
      and ferric chloride, at doses for optimum turbidity removal, provided little to
      no (<10%) removal of parent herbicides or neutral degradates. Chlorination with 6
      mg/L applied free chlorine for 6 h was able to achieve 100% removal of those
      degradates lacking an acetanilide substituent; compounds possessing this
      functional group exhibited low (0-16%) removal efficiencies. Products were
      generally not identified, except in the case of dimethenamid and its deschloro
      degradate, both of which formed a single ring-chlorination product on their ready
      reaction (84% and 96% removal, respectively) with aqueous chlorine species.
      Treatment with ozone at an applied dose of 3 mg/L for 30 min proved effective (60
      100%) at transforming all of the compounds under investigation to unidentified
      products. The parent herbicides and neutral degradates underwent adsorption by
      powdered activated carbon (PAC). Adsorption capacities (Freundlich K constants)
      correlated with K(ow) values.

PMID- 16290184
TI  - Removal of As(III) and As(V) from water using a natural Fe and Mn enriched
      sample.
AB  - The arsenic removal capacity of a natural oxide sample consisting basically of Mn
      minerals (birnessite, cryptomelane, todorokite), and Fe-oxides (goethite,
      hematite), collected in the Iron Quadrangle mineral province in Minas Gerais,
      Brazil, has been investigated. As-spiked tap water and an As-rich mining effluent
      with As-concentrations from 100 microg L(-1) to 100 mg L(-1) were used for the
      experiments. Sorbent fractions of different particle sizes (<38 microm to 0.5
      mm), including spherical material (diameter 2 mm), have been used. Batch and
      column experiments (pH values of 3.0, 5.5, and 8.5 for batch, and about pH 7.0
      for column) demonstrated the high adsorption capacity of the material, with the
      sorption of As(III) being higher than that of As(V). At pH 3.0, the maximum
      uptake for As(V) and for As(III)-treated materials were 8.5 and 14.7 mg g(-1),
      respectively. The Mn-minerals promoted the oxidation of As(III) to As(V), for
      both sorbed and dissolved As-species. Column experiments with the cFeMn-c sample
      for an initial As-concentration of 100 microg L(-1) demonstrated a very efficient
      elimination of As(III), since the drinking water limit of 10 microg L(-1) was
      exceeded only after 7400 BV total throughput. The As-release from the loaded
      samples was below the limit established by the toxicity characteristic leaching
      procedure, thus making the spent material suitable for discharge in landfill
      deposits.

PMID- 16290185
TI  - Consequences of mass transfer effects on the inetics of nitrifiers.
AB  - The influence of membrane separation and mass transfer effects on the kinetics of
      nitrifiers was evaluated by running a membrane bioreactor (MBR) and a
      conventional activated sludge (CAS) plant in parallel. Both pilot plants were
      operated at the same sludge age and treated the same domestic wastewater. The
      half-saturation constants for the substrate were low in both MBR and CAS and did
      not differ significantly between the two processes (K(NH(4))) and 0.14+/-0.10
      g(N)m(-3) and (K(NO(2))) and 0.28+/-0.20 g(N)m(-3) for the MBR and CAS,
      respectively). However, the half-saturation constants for oxygen exhibited a
      major difference between the two processes for both the ammonia-oxidizing (AOB)
      and nitrite-oxidizing (NOB) bacteria. The experiments yielded K(O,AOB)=0.18+/
      0.04 and 0.79+/-0.08 g(O2) as well as K(O,NOB)=0.13+/-0.06 and 0.47+/-0.04 g(O2)
      m(-3) (substrate only NO(2)) for the MBR and CAS, respectively. The higher K(0)
      values of the CAS were attributed to mass transfer effects within the large flocs
      prevailing in the conventional system. In contrast, the sludge from the MBR
      consisted of very small flocs for which the diffusion resistance can be
      neglected. On the basis of these results, the implementation of mass transfer
      effects in activated sludge models is discussed and consequences for the
      operation of MBRs are highlighted.

PMID- 16290186
TI  - Comparison and evolution analysis of two rice subspecies LATERAL ORGAN BOUNDARIES
      domain gene family and their evolutionary characterization from Arabidopsis.
AB  - The plant specific LATERAL ORGAN BOUNDARIES (LOB) domain (LBD) gene family has a
      potential role in lateral organ development. Thirty-five LBD genes in a japonica
      rice (Nipponbare) (designated OsJLBD) and in an indica rice (9311) (designated
      OsILBD) were identified based on the current databases of the two rice
      subspecies. A new rice LBD gene with two LOB domains and two predicted coiled
      coil structures in both subspecies was found, which is not found in other plant
      species based on the current NCBI Genbank database. OsJLBD and OsILBD genes have
      similar chromosomal distribution pattern. Both OsJLBD and OsILBD genes can be
      divided into 7 subclasses (classes Ia-e, II and III (see )) and no subclass
      specific expression pattern was observed. No introns have been predicted in all
      class Ie genes in both OsJLBD and OsILBD subfamilies. The genome and tandem
      duplication has contributed to the neofunctionalization and formation of new rice
      subclasses, but the mechanism of diploidization and limited tandem duplication
      have contributed to fewer LBD genes in rice than in Arabidopsis. Functional
      studies of genes in subclasses may help to determine whether special sequence
      structure (intron-exon, spacing characters of motifs) has caused special
      expression pattern of subclasses.

PMID- 16290187
TI  - Integrated understanding of urban land, groundwater, baseflow and surface-water
      quality--the City of Birmingham, UK.
AB  - Integrated understanding of urban land, groundwater (shallow and deep), baseflow
      and surface-water quality relationships is required for effective urban water
      quality management. Chemical quality data from across these media have been
      collected for the Birmingham (UK) aquifer--River Tame conurbation to assess
      chemical transport from contaminated land to groundwater to baseflow to surface
      water. Although metals concentrations were high in soils, low leachability and
      attenuation caused concentrations in groundwaters and baseflow discharging to
      surface water to be generally low with only sporadic elevated concentrations
      attributed to localised point sources. Hydrocarbon VOCs (volatile organic
      compounds) were similarly absent or at low concentration attributable to their
      ready natural attenuation. Chlorinated VOCs, however, were widely encountered in
      groundwater, discharging as baseflow to surface water and impacting surface-water
      quality. This is attributed to their DNAPL (dense nonaqueous-phase liquid)
      properties and relative recalcitrance although there was some evidence of
      biodegradation, albeit insufficient to protect surface water and groundwater
      abstraction receptors. Some inorganic trends were evident across the various
      media; nitrate was the most significant quality concern. Generic conclusions are
      drawn on urban water-quality management and the need for risk-based management
      strategies to optimise use of urban, sporadically contaminated groundwater in
      conjunction with surface water highlighted.

PMID- 16290188
TI  - Organic pollutants in wild ducks from New York state: I. Interspecies differences
      in concentrations and congener profiles of PCBs and PCDDs/PCDFs.
AB  - Wild ducks of three species, common mergansers (Mergus merganser americanus),
      gadwalls (Anas streptera), and mallards (Anas platyrhynchos), were collected near
      industrial sites in the Massena, NY area of the St. Lawrence River (SLR) in
      1988/89 and 1994. Additional samples were collected in 1994 near a former
      polychlorinated biphenyl (PCB) capacitor plant at Fort Edward, NY (a mallard and
      two wood ducks (Aix sponsa)), and at control sites (common mergansers, mallards
      and wood ducks). On a lipid basis, PCB concentrations in liver tissue from the
      1994 collection ranged from 0.1 mug/g in a control wood duck to 676 mug/g in a
      common merganser from the SLR area. However, the highest total polychlorinated
      dibenzofuran (PCDF) concentrations were found in liver and fat tissues of
      gadwalls and mallards collected near the SLR industrial sites (2.8-12 ng/g
      lipid). These two species bioaccumulated non-2,3,7,8-substituted PCDFs in
      addition to 2,3,7,8-PCDF isomers, whereas common mergansers preferentially
      bioaccumulated 2,3,7,8-substituted PCDFs. The mergansers from the SLR sites were
      the only specimens contaminated with polychlorinated dibenzo-p-dioxins (PCDDs),
      which were all 2,3,7,8-substituted. The PCB and PCDF congener patterns in the
      duck tissues appear to have been influenced by both sampling location and species
      trophic level.

PMID- 16290189
TI  - Regulation of matrix metalloproteinase expression by dynamic tensile strain in
      rat fibrochondrocytes.
AB  - OBJECTIVE: We sought to determine the molecular basis for the anticatabolic
      effects of mechanical signals on fibrocartilage cells by studying the expression
      of a variety of matrix metalloproteinases (MMPs). Furthermore, we examined
      whether the effects of biomechanical strain on MMP gene expression are sustained.
      METHODS: Fibrochondrocytes from temporomandibular joint (TMJ) discs were exposed
      to dynamic tensile strain for various time intervals in the presence of
      interleukin (IL)-1beta. The regulation of the messenger RNA (mRNA) expression and
      synthesis of MMPs and tissue inhibitors of MMPs (TIMPs) were examined by end
      point and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) as
      well as Western blot analysis. RESULTS: Fibrochondrocytes expressed mRNA for MMP
      2, -3, -7, -8, -9, -11, -13, -14, -16, -17, and -19 as well as TIMP-1, -2, and 
      3, IL-1beta induced a significant (P<0.05) upregulation of mRNA for MMP-3, -7, 
      8, -9, -13, -16, -17, and -19. The IL-1beta-stimulated upregulation of these MMPs
      was significantly (P<0.05) abrogated by dynamic tensile strain. However, MMP-2, 
      11, -14, and TIMPs were not affected by either IL-1beta or tensile strain.
      Biomechanical strain also inhibited the IL-1beta-stimulated protein synthesis of
      MMP-3, -7, -8, -9, -13, -16, and -17. Application of mechanical strain for
      various time intervals during a 24-h incubation with IL-1beta showed that the
      suppressive effects of mechanical signals are sustained. CONCLUSIONS: The data
      provide evidence that biomechanical signals can downregulate the catabolic
      activity of fibrocartilage cells in an inflammatory environment by inhibiting the
      expression of a variety of MMPs. Furthermore, the matrix-protective effects of
      biomechanical signals are sustained even in an inflammatory environment.

PMID- 16290190
TI  - Semen and reproductive profiles of genetically identical cloned bulls.
AB  - In this comparative study, reproductive parameters and semen characteristics of
      cloned bulls (n = 3) derived from somatic cell nuclear transfer (SCNT) were
      compared to their original cell donor Holstein-Friesian (n = 2) bulls from the
      same enterprise to assess the differences in reproductive potential between a
      donor bull and its clones. The parameters evaluated included motility of fresh,
      frozen-thawed and Percoll-treated frozen-thawed spermatozoa, as well as in vitro
      fertilization (IVF) ability, embryo quality, birth and survival of calves
      following IVF and embryo transfer with frozen-thawed semen. With fresh semen,
      spermatozoa from one cloned bull had lower motility than its donor. Cloned bulls
      had higher velocity parameters in fresh semen, but those effects were not obvious
      in frozen-thawed or frozen-thawed semen selected with a Percoll gradient. Semen
      collected from cloned bulls had significantly higher IVF rates compared to
      donors; however, embryo development per cleaved embryo or quality of blastocysts
      did not differ between donors and cloned bulls. Pregnancy and live offspring
      rates from one donor and its cloned bull did not differ between fresh (40%, 16/40
      versus 46%, 17/37) and vitrified/thawed (13%, 2/16 versus 25%, 4/16) embryo
      transfer following IVF. A total of 26 calves were obtained from genotypically
      identical donor and cloned bulls with no signs of phenotypical abnormalities.
      These preliminary results suggested that the physiology of surviving postpubertal
      cloned bulls and quality of collected semen had equivalent reproductive potential
      to their original cell donor, with no evidence of any deleterious effects in
      their progeny.

PMID- 16290192
TI  - Muscarinic suppression in stratum radiatum of CA1 shows dependence on presynaptic
      M1 receptors and is not dependent on effects at GABA(B) receptors.
AB  - Cholinergic modulation of synaptic transmission is vital to memory processes and
      may be responsible for setting network dynamics in the hippocampus appropriate
      for encoding of information. found evidence suggesting M1 receptors cause
      presynaptic inhibition of glutamatergic transmission, while research supports a
      role of the M2 receptor. We examined muscarinic inhibition of fEPSPs in stratum
      radiatum of mice lacking m1 subtype receptors (KO) compared to wild type (WT)
      controls. WT mice exhibit greater suppression of transmission by muscarine as
      compared to KO in a dose dependent fashion. Oxotremorine shows no significant
      difference in suppression between WT and KO, while MCN-A-343, an M1 agonist,
      exhibits a significant difference between KO and WT, with KO showing no
      suppression. One hundred micromolar SGS-742, a selective GABA(B) antagonist,
      fails to affect either normal transmission or muscarinic suppression in either WT
      or KO suggesting that differences in suppression between the groups is not
      attributable to differences in GABA(B) receptor activation due to muscarinic
      activation of GABAergic interneurons. These findings support a role for
      presynaptic m1 mAChRs in modulation of synaptic transmission in CA1, but indicate
      that other muscarinic receptor subtypes, such as M2, are also involved in
      suppression of synaptic potentials.

PMID- 16290193
TI  - Wistar rats show episodic-like memory for unique experiences.
AB  - Human episodic memory refers to the recollection of an unique past experience in
      terms of its details, its locale, and temporal occurrence. Episodic memory, even
      in principle, has been difficult to demonstrate in non-verbal mammals.
      Previously, we provided evidence that mice are able to form an integrated memory
      for "what," "where," and "when" aspects of single experiences by combining
      different versions of the novelty-preference paradigm, i.e., object recognition
      memory, the memory for locations in which objects were explored, and the temporal
      order memory for objects presented at distinct time points. In the present series
      of experiments we evaluated whether this paradigm, with minor modifications, also
      works with rats. We found that rats spent more time exploring an "old familiar"
      object relative to a "recent familiar" object, suggesting that they recognized
      objects previously explored during separate trials and remembered their order of
      presentation. Concurrently, the rats responded differentially to spatial object
      displacement dependent on whether an "old familiar" or "recent familiar" object
      was shifted to a location, where it was not encountered previously. These results
      provide strong evidence that the rats established an integrated memory for
      "what," "where," and "when." We also found that acute stress impaired the
      animal's performance in the episodic-like memory task, which, however, could be
      partially reversed by the N-Methyl-D-aspartate-receptors agonist D-cycloserine.

PMID- 16290194
TI  - Effect of Morris water maze diameter on visual-spatial learning in different
      mouse strains.
AB  - The Morris water maze task is a widely used tool to assess hippocampus-dependent
      learning and memory in rodents. Performance depends upon several factors
      including not only the traits of the experimental animals, but also apparatus and
      protocol characteristics. The present study aimed at investigating the effect of
      maze diameter on acquisition and probe trial performance in three commonly used
      strains: C57Bl/6, BALB/c, and 129/SvEvBrd mice. Three maze diameters (150, 120,
      and 75 cm) were used under identical protocol and testing conditions. Downscaling
      maze dimensions, hence reducing difficulty and stress levels, did not allow
      BALB/c mice, commonly known as poor learners, to acquire this visual-spatial
      learning task. C57Bl/6 mice performed satisfactory in all three maze settings,
      with superior probe trial performance in the 120-cm-diameter setting. Further
      downscaling of maze dimensions might even render this task too simple for this
      strain. If the 129S5/SvEvBrd background strain is preferred, testing of visual
      spatial learning abilities should be performed in a small sized MWM pool, as this
      strain performed only adequately in the smallest maze setting. Attention is drawn
      to the importance of supplying a detailed description 129 substrain nomenclature
      in future studies. Generalization of observations from one strain to another and
      from data obtained with a specific strain and maze diameter to other maze
      dimensions should be dealt with very carefully. The present study emphasizes the
      importance of a well-substantiated choice of background strain and water maze
      characteristics when researchers plan to investigate visual-spatial learning and
      memory in a chemically/lesion-induced or targeted mutagenesis model.

PMID- 16290195
TI  - The entorhinal cortex plays a role in extinction.
AB  - In this study, we analyzed the participation of the entorhinal cortex in
      extinction of a learned aversive response. Rats with infusion cannulae aimed to
      the entorhinal cortex were trained in a one-trial step-down inhibitory avoidance
      task (IA) and submitted to four consecutive daily test sessions without the
      footshock, a procedure that induced extinction of the conditioned response in
      control animals. When infused into the entorhinal cortex immediately after the
      first extinction session at doses able to block consolidation of IA memory, the
      NMDA receptor antagonist, AP5 (25 nmol/side), the inhibitor of protein synthesis
      anisomycin (300 nmol/side) and the inhibitor of CaMKII, KN-93 (10 nmol/side), but
      not the MEK1/2 inhibitor PD-98059 (5 nmol/side) hindered extinction of the IA
      response. The same results were obtained when the interval between the first and
      second test session was 48 instead of 24h. The data indicate that normal
      functionality of the NMDA receptors, together with CaMKII activity and protein
      synthesis are necessary in the entorhinal cortex at the time of the first test
      session to generate extinction. Our results also suggest that the ERK1/2 pathway
      does not play a role in this process.

PMID- 16290196
TI  - Diagnostic ability of optical coherence tomography with a normative database to
      detect localized retinal nerve fiber layer defects.
AB  - PURPOSE: To evaluate the diagnostic ability of third-generation optical coherence
      tomography (Stratus OCT) with a normative database to detect localized retinal
      nerve fiber layer (RNFL) defects. DESIGN: Cross-sectional study. PARTICIPANTS:
      One eye of each of 55 subjects (43 normal-tension glaucoma and 12 primary open
      angle glaucoma subjects) with localized, wedge-shaped RNFL defects by red-free
      RNFL photographs and corresponding visual field defects (mean deviation, -6.77+/
      3.54; range, -1.25 to -9.20 dB). METHODS: The segments of the borderline and
      outside normal limits in the RNFL thickness profile of OCT were considered to be
      significant RNFL defects by OCT and by comparison with their corresponding red
      free RNFL photographs. The angular locations and widths of RNFL defects by OCT
      were compared with those of RNFL defects by red-free RNFL photographs. MAIN
      OUTCOME MEASURES: Sensitivity and specificity of OCT with a normative database to
      detect the localized RNFL defects. RESULTS: The mean age of the patients was
      57.9+/-10.6 years (range, 25-78 years). The overall sensitivity and specificity
      of the OCT with a normative database for detecting localized RNFL defects were
      85.9% and 97.4%, respectively. The OCT with a normative database showed good
      diagnostic agreement with red-free RNFL photographs (overall kappa value = 0.79).
      The angular locations and widths of RNFL defects by OCT were highly correlated
      with those of RNFL defects by red-free RNFL photographs (Pearson correlation
      coefficient [r] = 0.996 and 0.725, respectively). CONCLUSIONS: The OCT with a
      normative database can detect localized RNFL defects with moderate sensitivity
      and high specificity, and shows good diagnostic agreement with red-free RNFL
      photographs.

PMID- 16290197
TI  - Consumption of mannan-binding lectin during abdominal aortic aneurysm repair.
AB  - OBJECTIVE: Patients undergoing abdominal aortic aneurysm (AAA) repair are exposed
      to an ischaemia-reperfusion injury (IRI), which is in part mediated by complement
      activation. We investigated the role of the novel lectin pathway of complement
      during IRI in patients undergoing AAA repair. METHODS: Patients undergoing
      elective open infrarenal AAA repair had systemic blood samples taken at induction
      of anaesthesia, prior to aortic clamping, prior to aortic declamping and at
      reperfusion. Control patients undergoing major abdominal surgery were also
      included. Plasma was assayed for levels of mannan-binding lectin (MBL) using
      ELISA techniques. Consumption of plasma MBL was used as a measure of lectin
      pathway activation. RESULTS: Twenty-three patients undergoing AAA repair and
      eight control patients were recruited. No lectin pathway activation could be
      demonstrated in the control patients. AAA patients experienced a mean decrease in
      plasma MBL levels of 41% representing significant lectin pathway activation (p =
      0.003). CONCLUSION: Consumption of MBL occurs during AAA repair, suggesting an
      important role for the lectin pathway in IRI. Specific transient inhibition of
      lectin pathway activity could be of significant therapeutic value in patients
      undergoing open surgical AAA repair.

PMID- 16290198
TI  - Vesicular roundness and compound release in PC-12 cells.
AB  - The principal goals of this study were to establish a quantitative morphological
      analysis of spatial and regional properties of dense core vesicles, and to use
      this analysis to assess whether homotypic fusion is prominent in chronically
      treated PC-12 cells at elevated release levels. Simple computerized image
      processing of electron-micrographs provided the binary images of vesicular dense
      cores, whilst the artificial intelligence methods were needed to determine the
      vesicular membranes. As in the past, the presence of large, highly irregular
      vesicles, provided the morphological evidence of fused vesicles, but the
      irregularity of vesicular shape was assessed quantitatively-from its roundness.
      Free space of each vesicle was determined from the distance to its nearest
      neighbor, or from the size of its Voronoi polygon. Within a Voronoi polygon, each
      point is closer to that vesicle than to any other vesicle. Large vesicles were
      not less round and did not have larger free space, as expected if they result
      from fusion of several smaller vesicles. In conclusion, we present a novel and
      rigorous morphological analysis of spatial and regional properties of dense core
      vesicles. The results demonstrate that the homotypic fusion is not prominent in
      PC-12 cells, before or following a chronic treatment that enhances release.

PMID- 16290199
TI  - Nanobiolistic delivery of indicators to the living mouse retina.
AB  - The development of a technique to load functional indicators into living neurons
      is an ongoing challenge in retinal neurophysiology. In a number of live-cell
      preparations, fluorescence-based indicators have been of particular importance
      for investigating ionic concentrations, protein localization, and other
      physiological parameters. In the present study, we demonstrate a novel technique
      that uses a modified gene gun to propel silver nanoparticles coated with
      indicators into live retinal neurons, and we highlight the advantages of using
      this technique to deliver these functional indicators.

PMID- 16290200
TI  - Use of a force-plate actometer for detecting and quantifying vertical leaping
      induced by amphetamine in BALB/cJ mice, but not in C57BL/6J, DBA/2J, 129X1/SvJ,
      C3H/HeJ, and CD-1 mice.
AB  - The force-plate actometer is a relatively new computer-based instrument with high
      temporal and spatial resolution that has been used to measure the behavioral
      effects of genetic restriction (e.g., inbred mice) and drugs (e.g., dopaminergic
      agonists and antagonists) on a variety of behaviors in rodents, including
      locomotor activity, stereotypies, tremor, and wall rearing. In the present study,
      the force-plate actometer was used to measure the differential effects of
      amphetamine-induced (10.0mg/kg) vertical leaping in five inbred mouse strains
      (BALB/cJ, C57BL/6J, DBA/2J, 129X1/SvJ, and C3H/HeJ) and one outbred stock (CD-1).
      Across a 13-day, five-injection procedure, mice of the BALB/cJ strain leaped an
      average of 82 times per 60-min session; the C57BL/6J, DBA/2J, 129X1/SvJ, C3H/HeJ
      strains and CD-1 stock always showed zero or near zero levels of vertical leaping
      following amphetamine treatment. The quantitative precision afforded by the force
      plate actometer revealed that the mean duration of the leaps by the BALB/cJ
      strain was 0.18 second, and the corresponding peak force averaged 87.4 gram per
      leap, which was more than 400% of the average body weight of this strain.
      Although no evidence of behavioral sensitization was indicated for amphetamine's
      effects on vertical leaping, sensitization to amphetamine's effects on spatial
      confinement (i.e., bouts of low mobility) was observed in all mouse types.
      Results indicate that the force-plate actometer is an instrument well suited for
      detecting and quantifying both vertical leaping and collateral behaviors induced
      by amphetamine in mice.

PMID- 16290201
TI  - Quantitative structure-pharmacokinetic relationships for drug clearance by using
      statistical learning methods.
AB  - Quantitative structure-pharmacokinetic relationships (QSPkR) have increasingly
      been used for the prediction of the pharmacokinetic properties of drug leads.
      Several QSPkR models have been developed to predict the total clearance (CL(tot))
      of a compound. These models give good prediction accuracy but they are primarily
      based on a limited number of related compounds which are significantly lesser in
      number and diversity than the 503 compounds with known CL(tot) described in the
      literature. It is desirable to examine whether these and other statistical
      learning methods can be used for predicting the CL(tot) of a more diverse set of
      compounds. In this work, three statistical learning methods, general regression
      neural network (GRNN), support vector regression (SVR) and k-nearest neighbour
      (KNN) were explored for modeling the CL(tot) of all of the 503 known compounds.
      Six different sets of molecular descriptors, DS-MIXED, DS-3DMoRSE, DS-ATS, DS
      GETAWAY, DS-RDF and DS-WHIM, were evaluated for their usefulness in the
      prediction of CL(tot). GRNN-, SVR- and KNN-developed models have average-fold
      errors in the range of 1.63 to 1.96, 1.66-1.95 and 1.90-2.23, respectively. For
      the best GRNN-, SVR- and KNN-developed models, the percentage of compounds with
      predicted CL(tot) within two-fold error of actual values are in the range of 61.9
      74.3% and are comparable or slightly better than those of earlier studies. QSPkR
      models developed by using DS-MIXED, which is a collection of constitutional,
      geometrical, topological and electrotopological descriptors, generally give
      better prediction accuracies than those developed by using other descriptor sets.
      These results suggest that GRNN, SVR, and their consensus model are potentially
      useful for predicting QSPkR properties of drug leads.

PMID- 16290203
TI  - Theory of proteolytic antibody occurrence.
AB  - Antibodies (Abs) with proteolytic and other catalytic activities have been
      characterized in the blood and mucosal secretions of humans and experimental
      animals. The catalytic activity can be traced to nucleophilic sites of innate
      origin located in Ab germline variable regions. Discoveries of the natural
      chemical reactivity of Abs were initially met with bewilderment, as the notion
      had taken hold that catalytic activities can be introduced into Abs by artificial
      means, but somatically operative selection pressures are designed only to adapt
      non-covalent Ab binding to antigen ground states. Unsurprisingly, initial efforts
      to engineer Abs with catalytic activity were oriented towards improving the non
      covalent binding at the atoms immediately within the transition state reaction
      center. Slowly, however, dogmatic approaches to Ab catalysis have given way to
      the realization that efficient and specific catalytic Abs can be prepared by
      improving the natural nucleophilic reactivity combined with non-covalent
      recognition of epitope regions remote from the reaction center. The field remains
      beset, however, with controversy. This article attempts to provide a rational
      basis for natural Ab catalysis, in the hope that understanding this phenomenon
      will stimulate medical and basic science advances in the field.

PMID- 16290202
TI  - Non-tuberculous mycobacteria disease as a cause of hospitalization in HIV
      infected subjects.
AB  - OBJECTIVES: The present study characterized and determined the prevalence of
      mycobacterial diseases (tuberculosis (TB) and non-tuberculous mycobacteria (NTM))
      as a cause of hospitalization among HIV-infected subjects consecutively admitted
      to a large metropolitan hospital during 2001/2002. METHODS: Hospital discharge
      diagnoses were established for 521 HIV-positive patients. RESULTS: Respiratory
      disease accounted for 49% of the admissions. Community acquired pneumonia (CAP)
      was the main cause of respiratory disease (52%) followed by Pneumocystis carinii
      (PCP, 24%), non-tuberculous mycobacteria (NTM, 11%) and Mycobacterium
      tuberculosis (TB, 9%). Mycobacterium tuberculosis disease was established using
      bacteriological, clinical and radiographic criteria. NTM disease was defined
      following the American Thoracic Society criteria. NTM was disseminated in the
      majority of cases (19 Mycobacterium avium complex (MAC), one Mycobacterium
      kansasii). Nine patients had respiratory disease (seven MAC, one Mycobacterium
      fortuitum, one Mycobacterium kansasii) and one had gastrointestinal disease
      caused by MAC. Mortality was 10% for NTM disseminated cases; none of the TB
      patients died over the course of the study. The length of hospitalization for NTM
      patients was longer (15+/-13 days) than for other respiratory cases (10+/-10,
      p=0.04). CONCLUSIONS: NTM disease along with its related mortality is a
      significant pathology as a cause of hospitalization among HIV-infected
      individuals.

PMID- 16290204
TI  - T lymphocytes and dendritic cells are activated by the deletion of peroxiredoxin
      II (Prx II) gene.
AB  - Peroxiredoxin II (Prx II) is a member of antioxidant enzyme family and it plays a
      protective role against oxidative damage. Constitutive production of endogenous
      reactive oxygen species was detected in spleen and bone marrow cells lacking Prx
      II. Here, we investigated the role of Prx II in immune responses. The total
      number of splenocytes (especially, the population of S-phase cells and CD3(+) T
      cells) was significantly higher in Prx II(-/-) mice than in wild type. Number of
      peripheral blood mononuclear cells (PBMCs) in Prx II(-/-) mice was also higher
      than wild type. Differentiation of Prx II(-/-) mouse bone marrow cells into CD11c
      positive dendritic cells was greater than that of wild type. Transplantation of
      Prx II(-/-) bone marrow cells into wild type mice increased PBMCs in blood and
      bone marrow-derived dendritic cells. Prx II deletion enhances concanavalin A
      (ConA)-induced splenocyte proliferation and mixed lymphocyte reaction (MLR)
      activity of bone marrow-derived CD11c-positive dendritic cells to stimulate
      recipient splenocytes. Collectively, these data suggest that Prx II inhibits the
      immune cell responsiveness, which may be regulated by scavenging the low amount
      of reactive oxygen species (ROS).

PMID- 16290205
TI  - Strain differences in allele and expression levels of CD72 on B-lymphocytes from
      NOD, AKR, NON and C57BL/6 mice.
AB  - The B-lymphocyte marker CD72 has multiple alleles and serves crucial and
      nonredundant roles in B-cell development and activation. B-lymphocytes play an
      important role in development of autoimmune diabetes in NOD mice, therefore we
      examined the patterns of expression of CD72 and its alloantigens on splenic
      lymphocytes from 4-week-old NOD/LtJ mice. Comparisons of CD72 expression were
      made between NOD mice and three non-diabetic strains, NON/LtJ mice, C57BL/6J and
      AKR/J. Use of allele-specific monoclonal antibodies revealed that the previously
      uncharacterized NON strain expresses either the a or d allele, whereas NOD and
      AKR mice were confirmed to express the rare c allele. Flow cytometric analysis
      revealed differential expression between the strains. Whereas NON, C57BL/6 and
      AKR mice expressed CD72 on 98, 94 and 92% of their B-lymphocytes (CD19+ cells),
      the NOD mice only expressed this regulatory marker on 78% of their B-lymphocytes.
      Furthermore, CD72 expression levels on CD72 positive cells were lower in NOD mice
      than in other three non-diabetic strains. The presence of the CD72c allele, as
      well as its low level of expression in NOD mice at 4 weeks of age, may be
      associated with B-lymphocyte hyper-responsiveness and resistance to activation
      induced cell death.

PMID- 16290206
TI  - Inflammation of the respiratory tract is associated with CCL28 and CCR10
      expression in a murine model of allergic asthma.
AB  - Mouse models and in vitro cell culture were used to examine airway expression of
      the mucosal chemokine CCL28. Low levels of constitutively expressed mRNA were
      observed in transformed murine epithelial cells, but high levels could be induced
      by stimulation. Cytokines that signal through NF-kappaB, including IL-1beta and
      TNF-alpha or via JAK-STAT pathway including oncostatin M induced CCL28 in airway
      epithelial cells in vitro. Immunohistochemistry of murine airway tissue revealed
      that constitutive expression of CCL28 protein in vivo was low and not ubiquitous.
      However, abundant expression was detected in epithelia and lymphoid aggregates
      following allergic sensitization and challenge with ovalbumin. This was
      accompanied by increased detection of cells expressing CCR10 protein and mRNA in
      inflamed airways. Taken together, these data support a role for CCL28 in
      contributing to allergen driven airway pathologies, show that proinflammatory
      cytokines can induce this signal and suggest a role for CCR10 expressing cells in
      airway inflammation.

PMID- 16290207
TI  - Direct digital lateral cephalometry: the effects of JPEG compression on image
      quality.
AB  - OBJECTIVES: This study used an aluminium test object to assess the effect of the
      Joint Photographics Expert Group (JPEG) compression algorithm, on direct digital
      cephalometric image quality. METHODS: The aluminium block of 15 steps, with 20
      holes in each step was radiographed in a Planmeca Proline 2002 digital
      cephalometric machine with Dimaxis2 software. Six different JPEG compression
      ratios were used to capture the cephalometric images. These ratios were 60%, 70%,
      80%, 90%, TOP QUALITY JPEG (TQJPEG 98%) and TIFF (uncompressed). The images were
      taken at 68 kV and 12 mA with a 7 s exposure. Six experienced observers viewed
      the monitor displayed images, which were presented randomly. This was repeated
      one month later. The number of holes detected by each observer was plotted
      against each compression ratio. Intra-observer and inter-observer reproducibility
      was calculated using the Mann-Whitney U-test. Differences between the compression
      ratios were assessed using a Kruskal-Wallis one-way analysis of variance.
      RESULTS: When comparing intra-observer reproducibility, it was found that there
      were only four of 36 comparisons that showed a statistically significant
      difference (Observer 1: 60% (P=0.004), TQJPEG (P=0.019); Observer 2: TIFF
      (P=0.005); Observer 3: 90% (P=0.007)). Statistically, there was no significant
      difference with inter-observer reproducibility. There was no statistically
      significant difference between the image quality obtained from each compression
      ratio. CONCLUSIONS: The results showed that JPEG compression does not have any
      effect on the perceptibility of landmarks in the aluminium test object used in
      this study.

PMID- 16290208
TI  - Effects of prenatal stress on anxiety and social interactions in adult rats.
AB  - Deficits in social behavior are found in several neuro-psychiatric disorders with
      a presumed developmental origin. The aim of the present study is to determine if
      prenatal stress at a given day of gestation alters social behavior in adult
      offspring. Pregnant rats were exposed to an acute stress (presence of a cat)
      either at the 10th (S10), the 14th (S14) or the 19th (S19) gestational day. When
      adult, their offsprings were studied in anxiety, neophobic and social behaviors.
      The results showed that S10 and S19 rats were more anxious and less aggressive
      than control rats, while the anxious and aggressive behavior of S14 rats was
      similar to that of the control ones. It is suggested that day 14 of pregnancy is
      a hyposensitive period to stressful agents due to an important plasticity of the
      developing gross nervous structures.

PMID- 16290209
TI  - Retinal neurospheres prepared as tissue for transplantation.
AB  - The present work was conducted to study the cellular composition and
      developmental capacity of retinal neurospheres. Furthermore, the ability of
      grafted neurospheres to integrate into adult retinal tissue was studied in an in
      vitro model. Retinal progenitor cells isolated from rat embryos were expanded
      into neurospheres in vitro in the presence of basic fibroblast growth factor
      (bFGF), epidermal growth factor (EGF) and leukemia inhibitory factor (LIF).
      Neurospheres labeled with a lipophilic dye were placed onto explants, and tissue
      interactions were analyzed after 2-6 days of culture. Immunocytochemical analysis
      of neurospheres revealed the presence of neuronal and glial cells. Proliferating
      neuronal and glial cells were observed after 2 weeks, whereas the neuronal cell
      proliferation declined considerably after 4 weeks. Few apoptotic cells were
      observed in the neurospheres. Neurospheres cultured on explanted adult retina
      engrafted with the surrounding tissue, but progenitor cell migration into the
      explants was low. However, the grafted neurospheres appeared to limit the
      experimentally induced photoreceptor apoptosis in the surrounding explant tissue.

PMID- 16290210
TI  - A web-based multimedia spatial information system to document Aedes aegypti
      breeding sites and dengue fever risk along the US-Mexico border.
AB  - This paper describes a web-based multimedia spatial information system used to
      support a study of the re-invasion of Aedes aegypti, the mosquito vector for
      dengue fever, in the deserts of the southwest United States/northwest Mexico. The
      system was developed applying Open Geospatial Consortium and World Wide Web
      Consortium Open Specifications and using Open Source Software. The system creates
      a sensory-rich environment, one which allows users to interact with the system to
      explore connections among data (maps, remotely sensed images, text, graphs, 360
      degree panoramas and photos), visualize information, formulate their own
      interpretations, generate hypotheses and reach their own conclusions.

PMID- 16290211
TI  - Absolute quantitation of Marek's disease virus and Herpesvirus of turkeys in
      chicken lymphocyte, feather tip and dust samples using real-time PCR.
AB  - The further development of Taqman quantitative real-time PCR (qPCR) assays for
      the absolute quantitation of Marek's disease virus serotype 1 (MDV1) and
      Herpesvirus of turkeys (HVT) viruses is described and the sensitivity and
      reproducibility of each assay reported. Using plasmid DNA copies, the lower limit
      of detection was determined to be 5 copies for the MDV1 assay and 75 copies for
      the HVT assay. Both assays were found to be highly reproducible for Ct values and
      calculated copy numbers with mean intra- and inter-assay coefficients of
      variation being less than 5% for Ct and 20% for calculated copy number. The
      genome copy number of MDV1 and HVT viruses was quantified in PBL and feather tips
      from experimentally infected chickens, and field poultry dust samples.
      Parallelism was demonstrated between the plasmid-based standard curves, and
      standard curves derived from infected spleen material containing both viral and
      host DNA, allowing the latter to be used for absolute quantification. These
      methods should prove useful for the reliable differentiation and absolute
      quantitation of MDV1 and HVT viruses in a wide range of samples.

PMID- 16290212
TI  - Volatile science? Metabolic engineering of terpenoids in plants.
AB  - Terpenoids are important for plant survival and also possess biological
      properties that are beneficial to humans. Here, we describe the state of the art
      in terpenoid metabolic engineering, showing that significant progress has been
      made over the past few years. Subcellular targeting of enzymes has demonstrated
      that terpenoid precursors in subcellular compartments are not as strictly
      separated as previously thought and that multistep pathway engineering is
      feasible, even across cell compartments. These engineered plants show that insect
      behavior is influenced by terpenoids. In the future, we expect rapid progress in
      the engineering of terpenoid production in plants. In addition to commercial
      applications, such transgenic plants should increase our understanding of the
      biological relevance of these volatile secondary metabolites.

PMID- 16290213
TI  - Genomics-assisted breeding for crop improvement.
AB  - Genomics research is generating new tools, such as functional molecular markers
      and informatics, as well as new knowledge about statistics and inheritance
      phenomena that could increase the efficiency and precision of crop improvement.
      In particular, the elucidation of the fundamental mechanisms of heterosis and
      epigenetics, and their manipulation, has great potential. Eventually, knowledge
      of the relative values of alleles at all loci segregating in a population could
      allow the breeder to design a genotype in silico and to practice whole genome
      selection. High costs currently limit the implementation of genomics-assisted
      crop improvement, particularly for inbreeding and/or minor crops. Nevertheless,
      marker-assisted breeding and selection will gradually evolve into 'genomics
      assisted breeding' for crop improvement.

PMID- 16290214
TI  - Technological milestones from plant science to agricultural biotechnology.

PMID- 16290215
TI  - Plant functional genomics: beyond the parts list.

PMID- 16290216
TI  - Towards molecular breeding and improvement of rice in China.
AB  - China is the largest producer and consumer of rice in the world and a pioneer in
      applying hybrid rice technology. Although hybrid rice has contributed greatly to
      Chinese agriculture in the past decades, its potential to improve grain quality
      further is being questioned. However, to meet the challenges posed by severe crop
      damage by pests and diseases, the extensive use of pesticides and chemical
      fertilizers, and a shortage of water and energy, more elite rice cultivars are
      needed. In recent years, China has seen continued improvements in rice genetics,
      powered by functional genomics as a way forward to safeguard its rice production.
      Here, we briefly review the current status of rice breeding in China through
      strategies integrating hybrid rice technology, molecular marker-assisted
      breeding, functional genomics and genetically modified rice.

PMID- 16290217
TI  - Progress in the dissection and manipulation of vitamin E synthesis.
AB  - Tocochromanols are a group of four tocopherols and four tocotrienols that
      collectively constitute vitamin E, an essential nutrient in the human diet.
      Tocochromanols are only synthesized in oxygenic photosynthetic organisms.
      Although they have similar antioxidant activities in vitro, the individual
      tocochromanols vary widely in their in vivo vitamin E activities. During the past
      several years, mutant and transgenic approaches in model organisms, particularly
      in Arabidopsis thaliana and Synechocystis sp. PCC6803, have allowed the full
      complement of core pathway genes to be isolated and studied. Pathway engineering
      with these genes has provided significant insights into the molecular genetic and
      biochemical control of tocochromanol biosynthesis in plants. The resulting
      knowledge base is driving efforts to manipulate the levels of this essential
      nutrient in staple crops for populations in the developed and developing world.

PMID- 16290218
TI  - Plant biotechnology kicks off into the 21st century.

PMID- 16290219
TI  - Plant biotechnology in Europe: a changing environment and landscape.

PMID- 16290220
TI  - Plant-derived pharmaceuticals--the road forward.
AB  - Plant-derived pharmaceuticals are poised to become the next major commercial
      development in biotechnology. The advantages they offer in terms of production
      scale and economy, product safety, ease of storage and distribution cannot be
      matched by any current commercial system; they also provide the most promising
      opportunity to supply low-cost drugs and vaccines to the developing world.
      However, despite the promised benefits, the commercialization of plant-derived
      pharmaceutical products is overshadowed by the uncertain regulatory terrain,
      particularly with regard to the adaptation of good manufacturing practice
      regulations to field-grown plants. The success of such products also depends on
      careful negotiation of the intellectual property landscape, particularly the
      achievement of freedom-to-operate licenses for use in developing countries.

PMID- 16290221
TI  - Acute and chronic effects of carrier solvents in aquatic organisms: a critical
      review.
AB  - Recognising the scientific and regulatory need for testing relatively hydrophobic
      or 'difficult substances', the OECD currently recommends that selected organic
      solvents may be used in aquatic toxicity testing in order to help achieve more
      effective dispersion of the toxicant. The OECD recommends a maximum solvent
      concentration of 100 microl l(-1) (with specific gravity equivalents to 100
      microl l(-1) in parentheses) for acetone (79 mg l(-1)), dimethylformamide (95 mg
      l(-1)), dimethylsulfoxide (1.10 mg l(-1)), ethanol (78.9 mg l(-1)), methanol
      (79.2 mg l(-1)) and triethylene glycol (1.12 mg l(-1)). While this recommendation
      is supported by historical data, we have recently observed evidence that some
      solvents may affect the reproduction of certain fish species, and also impact
      biomarkers of endocrine disruption. This review presents available data on the
      effects of solvents in aquatic organisms, supplemented by relevant information
      from mammalian studies (e.g. effects on liver enzyme induction potentially
      altering the metabolism of sex hormones). In conclusion, it is recommended that
      maximum effort should be given to avoiding the use of carrier solvents wherever
      possible, for example through the use of saturation columns or other physical
      methods (e.g. stirring or ultrasonification). Where solvent use is necessary,
      however, it is recommended that in reproduction studies with aquatic organisms,
      the maximum solvent concentration should not exceed 20 microl l(-1) of dilution
      water.

PMID- 16290223
TI  - Early prediction of sustained viral responder and non-responder during interferon
      and ribavirin combination therapy in chronic hepatitis C.

PMID- 16290222
TI  - Toxic actions of dinoseb in medaka (Oryzias latipes) embryos as determined by in
      vivo 31P NMR, HPLC-UV and 1H NMR metabolomics.
AB  - Changes in metabolism of Japanese medaka (Oryzias latipes) embryos exposed to
      dinoseb (2-sec-butyl-4,6-dinitrophenol), a substituted dinitrophenol herbicide,
      were determined by in vivo (31)P NMR, high-pressure liquid chromatography (HPLC)
      UV, and (1)H NMR metabolomics. ATP and phosphocreatine (PCr) metabolism were
      characterized within intact embryos by in vivo (31)P NMR; concentrations of ATP,
      GTP, ADP, GDP, AMP and PCr were determined by HPLC-UV; and changes in numerous
      polar metabolites were characterized by (1)H NMR-based metabolomics. Rangefinding
      exposures determined two sublethal doses of dinoseb, 50 and 75 ppb, in which
      embryos survived from 1-day post fertilization (DPF) through the duration of
      embryogenesis. In vivo (31)P NMR data were acquired from 900 embryos in 0, 50,
      and 75 ppb dinoseb at 14, 62, and 110 h (n = 6 groups) after initiation of
      exposure. After 110 h, embryos were observed for normal development and hatching
      success, then either preserved in 10% formalin for growth analysis or flash
      frozen and extracted for HPLC-UV and (1)H NMR analysis. Dinoseb exposure at both
      concentrations resulted in significant declines in [ATP] and [PCr] at 110 h as
      measured by in vivo (31)P NMR (p < 0.01), HPLC-UV (p < 0.001) and NMR-based
      metabolomics. Reduced eye growth and diminished heart rate occurred in a
      concentration-dependent fashion. Metabolic effects measured by in vivo (31)P NMR
      showed a significant increase in orthophosphate levels (P(i); p < 0.05), and
      significant decreases in [ATP], [PCr] and the PCr/P(i) ratio (p < 0.05).
      Metabolomics revealed a dose-response relationship between dinoseb and endogenous
      metabolite changes, with both dinoseb concentrations producing significantly
      different metabolic profiles from controls (p < 0.05). Metabolic changes included
      decreased concentrations of ATP, PCr, alanine and tyrosine, and increased
      concentrations of lactate with medaka embryotoxicity. This study demonstrated
      that medaka embryos respond to dinoseb with significant changes in metabolism,
      reduced growth and heart rates, and increased abnormal development and post
      exposure mortality. All three analytical methods confirmed similar trends, and
      utilization of PCr to compensate for ATP loss was found to be a consistent
      indicator of sublethal stress-one that could be used to quantify stress
      associated with medaka embryotoxicity.

PMID- 16290224
TI  - The changes of fractional flow reserve after intracoronary nitrate and Nicorandil
      injection in coronary artery ectasia.

PMID- 16290225
TI  - Right heart failure due to an unroofed coronary sinus in an adult.
AB  - An unroofed coronary sinus is a rare congenital malformation with a strong
      association to a persistent left vena cava superior. In most cases it occurs
      together with complex cardiac anomalies such as left isomerism. We report on a 72
      year-old man with clinical signs of right heart failure caused by an isolated
      unroofed coronary sinus: The diagnosis was made by means of transesophageal
      echocardiography with contrast injection.

PMID- 16290226
TI  - Dynamic left ventricular outflow tract obstruction secondary to catecholamine
      excess in a normal ventricle.
AB  - Hypertrophic cardiomyopathy (HCM) is the most common cause of left ventricular
      outflow tract (LVOT) obstruction. The LVOT obstruction is a consequence of the
      asymmetric septal hypertrophy and the mitral systolic anterior motion (SAM),
      causing both of them a dynamic gradient in LVOT. LVOT obstruction has been
      observed also in other conditions like hypertensive hypertrophy, dehydration,
      sepsis, vasodilatation, excessive sympathetic stimulation, pericardial tamponade,
      and after mitral valve repair and aortic valve replacement for aortic stenosis.
      We report in this document the case of two patients who developed a significant
      gradient at LVOT in the context of amine treatment during their admission into
      the intensive unit care. In both, cases there were no gradient, significant
      hypertrophy or SAM at baseline cardiac evaluation. We have met only one case
      reported in the literature matching those conditions. In order to treat this type
      of patients properly, it is essential to take in consideration this pathology.

PMID- 16290227
TI  - Increased level of cardiorespiratory fitness blunts the inflammatory response in
      metabolic syndrome.
AB  - OBJECTIVE: The presence of metabolic syndrome is associated with a higher degree
      of inflammation. We sought to assess whether the higher levels of
      cardiorespiratory fitness attenuate the levels of inflammation in people with
      metabolic syndrome. RESEARCH DESIGN AND METHODS: We studied 449 consecutive
      asymptomatic men (47+/-7 years) who underwent a maximal treadmill exercise test
      according to the Bruce protocol. Cardiorespiratory fitness was divided into
      tertiles based on metabolic equivalents (METs). White blood cells (WBC) (x10(9)
      cells/L) count was used as marker of inflammation. RESULTS: In our study
      population, 23% of the participants had the metabolic syndrome. The WBC count
      increased (p < 0.0001 for trend) with increasing number of risk factors for
      metabolic syndrome; however there was an inverse relationship (p < 0.0001 for
      trend) with increasing tertiles of fitness (6.47 cells x 10(9) cells/L for lowest
      tertile and 5.7 x 10(9) cells/L for highest tertile). Multiple linear regression
      analyses demonstrated that as compared to individuals with no MS risk factor, the
      WBC count remained significantly higher in men with metabolic syndrome in first
      tertile (regression coefficient: 1.2, 95% CI 0.4-2.0, p = 0.003) and second
      tertile (regression coefficient: 0.61, 95% CI 0.4-2.0, p = 0.02) of
      cardiorespiratory fitness, respectively. However, in the highest tertile of
      fitness no increase in level of WBC count was observed with increasing metabolic
      syndrome risk factors. CONCLUSION: Our findings suggest that in people with
      metabolic syndrome an increased level of physical fitness might exert its
      beneficial effect via attenuating inflammation.

PMID- 16290228
TI  - Understanding the IL-23-IL-17 immune pathway.
AB  - Interleukin (IL)-23 is a heterodimeric cytokine closely related to IL-12. Yet,
      despite a strong structural relationship that includes a shared p40 subunit, this
      does not translate into functional similarity. In fact, the opposite is true, in
      that these two cytokines appear to have profoundly different roles in regulating
      host immune responses. It is now clear that IL-23 has key roles in autoimmune
      destruction in experimental allergic encephalomyelitis, collagen-induced
      arthritis and inflammatory bowel disease. IL-23 drives the development of
      autoreactive IL-17-producing T cells and promotes chronic inflammation dominated
      by IL-17, IL-6, IL-8 and tumor necrosis factor as well as neutrophils and
      monocytes. It is unlikely that IL-23 and its downstream effects evolved just to
      cause autoimmunity, but its real benefit to the host and the lineage relationship
      between IL-17-producing cells and T helper 1 cells remain unclear. By comparing
      the pathophysiological function of IL-12 and IL-23 in the context of host defense
      and autoimmune inflammation, we are beginning to understand the novel IL-23-IL-17
      immune pathway.

PMID- 16290229
TI  - Antibody-directed cell-type-specific delivery of siRNA.
AB  - Over the past four years, chemically synthesized short interfering RNA (siRNA)
      has become the standard tool for specific silencing of gene expression in vitro.
      The most difficult task in transferring this technology to an in vivo setting is
      to develop appropriate delivery strategies. With this aim, Song et al. recently
      reported the development of antibody-protamine fusion proteins as vehicles for
      receptor-directed delivery of siRNA. When a mixture of siRNA targeting tumor
      related genes was administered in this way, tumor growth was inhibited in an
      engineered melanoma model, demonstrating the therapeutic potential of this
      technology. However, several challenges remain to be overcome before targeted
      gene silencing can become a reality for patients.

PMID- 16290230
TI  - Hedgehog checkpoints in medulloblastoma: the chromosome 17p deletion paradigm.
AB  - Medulloblastomas often activate Hedgehog signaling inappropriately. The finding
      that mutations in components of this pathway are present only in few tumors
      suggests that additional genetic or epigenetic lesions can also lead to Hedgehog
      dysregulation. Chromosome 17p deletion, the most frequently detected genetic
      lesion in medulloblastoma, has recently been identified as a cause of
      unrestrained Hedgehog signaling. Such a deletion leads to the loss of
      REN(KCTD11), a novel Hedgehog antagonist, thus removing a checkpoint of Hedgehog
      dependent events during cerebellum development and tumorigenesis. The disruption
      of additional Hedgehog modulators that map to 17p suggests a rationale for a
      multitargeted therapeutic strategy aimed at interrupting the cooperative
      activation of the Hedgehog pathway.

PMID- 16290231
TI  - Stakeholder position paper: companion animal veterinarian.
AB  - The total quantity of use in companion animals is generally believed to be
      relatively small in comparison with antimicrobial use in food animals. Use in
      companion animals is principally for treatment, whereas the greater proportion of
      use in food animals is for prophylaxis, metaphylaxis and growth promotion.
      Therefore, it is important to collect data on end use in companion animals so
      that overall estimates of use in companion animals can be generated and separated
      from estimates for food animals. However, data from antimicrobial use in
      companion animals are extremely limited and no serious attempts to collect such
      data have ever been made in the United States. The lack of usage data in is
      concomitant with the dearth of information on antimicrobial resistance in
      companion animals. Companion animals have been involved in the transmission to
      humans of, or become infected with, foodborne zoonotic bacteria such as
      Salmonella and Campylobacter. Companion animals are an integral part of the
      ecology of antimicrobial resistance through their contact with food animals and
      exposure to antimicrobials for disease treatment and through contact with humans
      and the environment. In the practice of companion animal medicine, antimicrobial
      use data are important for understanding the potential impact on companion animal
      heath posed by antimicrobial resistance transferred from food animals, humans and
      the environment, and the threat to humans and other companion animals posed by
      antimicrobial use in companion animals. Basic information on the patterns and
      quantities of antimicrobial use in combination with resistance surveillance data,
      could help companion animal veterinarians understand the potential for
      development, or evidence of, an antimicrobial resistance problem in their
      practices, the role of companion animals in the overall epidemiology of
      antimicrobial resistance, and for comparison with local, regional, or national
      data. The combination of data from either a sentinel site system of clinics or a
      use survey with national data from the pharmaceutical industry should provide
      sufficient data to credibly estimate the total volume and patterns of
      antimicrobial use in companion animal medicine. The time and effort for use
      monitoring or to complete a survey would likely become burdensome. Practice
      management software now utilized at most companion animal clinics could be used
      to generate antimicrobial use data as well as patient population data as
      surrogate for the true population at risk for patient encounters in a companion
      animal practice.

PMID- 16290232
TI  - Association between levels of Toll-like receptors 2 and 4 and CD14 mRNA and
      allergy in pregnant women and their offspring.
AB  - The microbial environment in early infancy or even in utero may modulate the risk
      to develop allergic disease. Since Toll-like receptors (TLR) recognize microbial
      products, we hypothesized that maternal allergies may be associated with
      decreased levels of TLR2, TLR4 and CD14 mRNA in mothers and their offspring. 185
      healthy pregnant women from Germany (n = 48), Hungary (n = 50) and Spain (n = 87)
      were enrolled in a European multicenter study. Levels of TLR2, TLR4 and CD14 mRNA
      were quantified in maternal peripheral blood samples taken at delivery and
      placental cord blood samples. Numbers of TLR2+, TLR4+ and CD14+ monocytes were
      quantified by flow cytometry in 42 cord blood samples obtained from the German
      participants. Bivariate and multivariate regression analyses were performed.
      Maternal allergies were associated with significantly lower levels of TLR2/4/CD14
      mRNA in maternal blood and cord blood samples. Maternal and fetal TLR2/4/CD14
      mRNA levels were significantly correlated with each other (TLR2 r = 0.42; TLR4 r
      = 0.58; CD14 r = 0.54). The results suggest that maternal allergy status may
      affect allergic risk in offspring through a decreased expression of fetal
      TLR2/4/CD14.

PMID- 16290233
TI  - Commensal microbiota alter the abundance and TCR responsiveness of splenic naive
      CD4+ T lymphocytes.
AB  - The epidemiologic risk of certain systemic immunologic diseases is affected by
      commensal or environmental microbiota, but the cellular basis of the "hygiene
      hypothesis" is poorly understood. In this study, we demonstrate that composition
      of the commensal microbiota affects the functional state of the peripheral naive
      (CD62L(hi)CD44(lo)) T lymphocyte populations. Restricted flora (RF) mice (stably
      colonized with excess nonpathogenic Clostridium sp., and changes in other
      bacterial and fungal taxa) were distinguished after the neonatal period by a
      progressive deficiency in absolute numbers of naive CD4+ and CD8+ T lymphocytes.
      SPF and RF mice had comparable levels of memory CD4+ and CD8+ T cells. This
      phenotype was attributable to the altered levels of certain commensals and their
      products, since germ-free mice had normal absolute numbers of splenic CD4+ and
      CD8+ T cells and their respective naive and memory subsets. The naive CD4+ T cell
      subset was functionally distinguished in RF mice versus SPF mice by TCR
      hyperresponsiveness, pro-inflammatory cytokine production, and increased
      activation-induced cell death. Biochemically, these traits were associated with
      higher basal phosphorylation of the TCR signaling proteins ZAP-70, Lck, and LAT.
      These findings indicate that enteric microbial products, through unknown cellular
      circuitry, influence steps in CD4 T cell differentiation moderating basal TCR
      signaling and immune responsiveness.

PMID- 16290234
TI  - Body mass index and occupational attainment.
AB  - In this paper I investigate the impact of body mass index (BMI) on occupational
      attainment in England. Using pooled cross-sectional health survey data for 1997
      and 1998 I find using OLS that, conditional on a comprehensive set of individual
      and area covariates, BMI has a positive and significant effect on occupational
      attainment in males and a negative and significant effect in females. Subsequent
      analyses with different covariates show considerable variation in the results for
      males, while for females the effect of BMI is significant and negative
      irrespective of the covariates used. IV coefficients on the BMI measures are
      insignificant in all models, though I am unable to identify any endogeneity
      problems with respect to BMI.

PMID- 16290235
TI  - Drug discovery and sea hares: bigger is better.
AB  - Traditionally, small molecules (<1kDa) have dominated the study of the chemistry
      and chemical ecology of marine natural products. However, as reported in a recent
      publication, Yang and co-workers have isolated a 60-kDa antibacterial protein
      from the defensive secretions of the sea hare Aplysia californica. This protein,
      escapin, has been characterized as an l-amino acid oxidase with bacteriostatic
      and bacteriocidal activities. Their work highlights the largely untapped
      biomedical potential of marine organism-derived proteins and addresses the
      problems of supply associated with invertebrate natural products. It also leads
      to intriguing hypotheses about the ecological function(s) of the new protein.

PMID- 16290236
TI  - Second-generation replication-competent oncolytic adenovirus armed with improved
      suicide genes and ADP gene demonstrates greater efficacy without increased
      toxicity.
AB  - Replication-competent adenovirus-mediated suicide gene therapy has proven to be
      safe in humans when delivered intraprostatically. Although signs of efficacy are
      emerging, it is likely that further improvements will be needed before this
      technology will have widespread applicability in the clinic. Toward this end, we
      have developed a second-generation, replication-competent adenovirus (Ad5
      yCD/mutTK(SR39)rep-ADP) containing an improved yeast cytosine deaminase
      (yCD)/mutant(SR39) herpes simplex virus thymidine kinase fusion (yCD/mutTK(SR39))
      gene and the adenovirus death protein (ADP) gene. Relative to the first
      generation Ad5-CD/TKrep adenovirus, Ad5-yCD/mutTK(SR39)rep-ADP demonstrated
      greater tumor cell kill in vitro and significantly greater tumor control in
      preclinical models of human cancer. Quantification of transgene volume following
      direct injection of fadenovirus into human tumor xenografts and the naive canine
      prostate demonstrated that ADP enhanced adenoviral spread in vivo. Toxicology
      studies were performed to determine whether the improved yCD/mutTK(SR39) fusion
      and ADP genes increased toxicity. Intraprostatic injection of Ad5
      yCD/mutTK(SR39)rep-ADP did not result in significantly increased toxicity
      relative to the parental Ad5-CD/TKrep adenovirus, the latter of which has proven
      to be safe in two Phase I prostate cancer clinical trials. Together, these
      results provide the scientific basis for evaluating the safety and efficacy of
      the second-generation Ad5-yCD/mutTK(SR39)rep-ADP adenovirus in humans.

PMID- 16290237
TI  - Temporal variation in the control of goal-directed visuospatial attention in
      basal ganglia disorders.
AB  - A predictive central-cueing paradigm was used to compare visuospatial deficits in
      patients with Parkinson's (PD) and Huntington's diseases (HD), employing
      directionally valid and invalid visual cues over a range of stimulus onset
      asynchronies (SOA) to elicit a saccadic response. Compared to age-matched control
      groups, both PD and HD patients responded erroneously to cue stimuli more
      frequently, increasing significantly over longer SOAs. Both valid and invalid
      cues resulted in elevated latencies compared to un-cued visually guided saccades,
      the associated 'cost' of invalid cueing significantly greater than that for valid
      cueing, over all SOAs. Unlike control subjects, PD and HD patients demonstrated
      temporal variation with cue presentation. For PD patients, latencies following
      directionally invalid cues were significantly longer for intermediate SOAs,
      suggesting difficulty overcoming a build-up of inhibitory activity over time. No
      validity effect was found at 1000 ms. For HD patients, latencies for validly cued
      saccades with 150 ms SOAs were shorter than latencies for no-cue trials,
      representing a 'benefit' of valid cueing. For 500 ms SOAs latencies were
      comparably elevated following directionally valid and invalid cues, and for 1000
      ms SOAs neither cue condition resulted in increased latencies. These findings
      reflect the consequence of disruption to the balance of activity over the basal
      ganglia facilitatory and inhibitory pathways. Imbalance in PD resulted in
      difficulty sustaining goal-directed behaviour, and in HD, difficulty gating
      inappropriate behaviour.

PMID- 16290239
TI  - Peripheral targets influence sensory-motor connectivity in the neonatal spinal
      cord: sciatic nerve axotomy in Bax-deficient mice.
AB  - In neonatal animals, peripheral nerve axotomy induces cell death in the
      corresponding dorsal root ganglion neurons and motoneurons, indicating that
      trophic interactions between these neurons and their targets control neuronal
      survival at this age. However, axotomy-induced cell death masks the role of
      peripheral tissues in regulating the central connections between these neurons in
      neonates. Since we have shown in Bax-deficient mice (Bax-/-) that transection of
      the sciatic nerve at postnatal day (P) 0 rarely induced apoptosis in motoneurons,
      we examined whether peripheral nerve axotomy eliminates synaptic connections
      between group Ia afferents and motoneurons in Bax-/-. After the axotomy, we
      observed in P7 Bax-/- that many axons survived in the fourth lumber (L4) dorsal
      root and that primary afferent projections to L4 motor pools also remained.
      Sciatic nerve stimulation evoked synaptic responses in L4 ventral roots in these
      mice although the amplitudes were considerably smaller and the onset latencies
      longer compared with the controls. Our results suggest that the monosynaptic
      connection between group Ia afferents and motoneurons is morphologically and
      functionally preserved following axotomy. Peripheral tissues may modulate
      synaptic connectivity but do not contribute to the maintenance of primary
      afferent projections in the stretch reflex pathway at an immature stage.

PMID- 16290238
TI  - Third pathway in the cortico-basal ganglia loop: Neurokinin B-producing striatal
      neurons modulate cortical activity via striato-innominato-cortical projection.
AB  - In the cortico-basal ganglia loop, striatal regions serve as 'entrances' to the
      basal ganglia, receiving massive inputs from the cerebral cortex and sending
      'direct' and 'indirect' pathways to the output nuclei of the basal ganglia.
      However, we have recently identified a new striatofugal subgroup which produces
      neurokinin B (NKB). Although NKB-producing neurons constitute a minority of
      striatal neurons, this subgroup is distinguished by the unique distribution and
      chemical characteristics. NKB-producing striatal neurons are distributed in
      association with mu-opioid receptor localization, and rarely express DARPP32,
      which is produced by the major striatofugal neurons and coupled with dopaminergic
      signaling. Further interestingly NKB-producing striatal neurons send axons to
      basal forebrain regions, but not to the main target regions of striatal outflow,
      pallidal or mesencephalic regions. In the basal forebrain, some GABAergic
      inhibitory neurons express NK3 receptor, selective receptor for NKB, and directly
      send axons to the cerebral cortex. The NK3-expressing neurons show different
      electrical properties from cholinergic basal forebrain neurons, and display
      facilitatory responses to stimulation of NK3 receptor. These findings strongly
      suggest that NKB-producing striatal neurons and NK3-expressing basal forebrain
      neurons constitute a third pathway which bypasses the common output nuclei of the
      basal ganglia, and more directly control or modulate cortical activity.

PMID- 16290240
TI  - Survey of public awareness, attitudes, and understanding toward epilepsy in Nhan
      Chinh, Hanoi, Vietnam, in 2003.
AB  - PURPOSE: Many studies have shown that cultural and social awareness of, attitudes
      toward, and knowledge about epilepsy can have an impact on the acceptance of
      treatment. The aim of this study is to characterize public awareness of attitudes
      toward and understanding of epilepsy in a Vietnamese community and to compare
      results with those obtained in other cultures. METHODS: A survey concerning the
      knowledge, attitudes, and practices of Vietnamese people with respect to epilepsy
      was carried out in the Nhan Chinh precinct of Hanoi. One thousand people were
      randomly selected for face-to-face interviews regarding epilepsy. RESULTS: Of the
      subjects surveyed, 54.6% had heard of epilepsy; 45.5% knew someone with epilepsy;
      49.2% had witnessed an epileptic seizure; 56% would not allow their son or
      daughter to marry someone with epilepsy; 42.1% did not believe that epileptic
      patients could hold down a normal job; 77.8% believed that epilepsy is an organic
      disorder of the brain; 23.8% thought that epilepsy is a form of dementia; and 91%
      thought that epileptic patients require medical care. CONCLUSION: As compared
      with surveys conducted in other countries, our survey showed that the awareness
      of epilepsy in this Vietnamese community is limited, and gives rise to
      alternative attitudes and practices.

PMID- 16290241
TI  - The opinion of the general practitioner toward clinical management of patients
      with psychogenic nonepileptic seizures.
AB  - OBJECTIVE: The purpose of this work was to assess the opinion of general
      practitioners (GPs) regarding the diagnosis of psychogenic nonepileptic seizures
      (PNES) and the role they feel they should play in the management of the disorder.
      METHODS: Patients with PNES were identified from hospital records. Seizure and
      patient characteristics were recorded. Their GPs were surveyed regarding their
      understanding of the diagnosis and ongoing management of PNES. RESULTS: Twenty
      three patients were identified over a 3-year period as having been diagnosed with
      PNES. Sixty-five percent of GPs agreed with the diagnosis, and when asked to
      grade their understanding of the diagnosis (poor = 1, excellent = 10), the mean
      score was 5.7 (+/-SD 2.3). Thirty-five percent of GPs felt psychological input
      was of benefit to their patients. Fifty-two percent of GPs felt comfortable
      following up these patients, either with or without neurology outpatient
      services. CONCLUSIONS: PNES remains a difficult disease to manage. There is a
      high level of uncertainty regarding the optimum management of PNES among primary
      care physicians, for which further education is needed.

PMID- 16290242
TI  - Methane fermentation of Japanese cedar wood pretreated with a white rot fungus,
      Ceriporiopsis subvermispora.
AB  - Methane fermentation of Japanese cedar wood was carried out after pretreatment
      with four strains of white rot fungi, Ceriporiopsis subvermispora ATCC 90467, CZ
      3, CBS 347.63 and Pleurocybella porrigens K-2855. These fungi were cultivated on
      wood chip media with and without wheat bran for 4-8 weeks. The pretreated wood
      chip was fermented anaerobically with sludge from a sewage treatment plant.
      Pretreatments with C. subvermispora ATCC 90467, CZ-3 and CBS 347.63 in the
      presence of wheat bran for 8 weeks decreased 74-76% of beta-O-4 aryl ether
      linkages in the lignin to accelerate production of methane. After fungal
      treatments with C. subvermispora ATCC 90467 and subsequent 30-days methane
      fermentation, the methane yield reached 35 and 25% of the theoretical yield based
      on the holocellulose contents of the decayed and original wood, respectively. In
      contrast, treatment with the three strains of C. subvermispora without wheat bran
      cleaved 15-26% of the linkage and produced 6-9% of methane. There were no
      significant accelerating effects in wood chips treated with P. porrigens which
      has a lower ability to decompose the lignin. Thus, it was found that C.
      subvermispora, with a high ability to decompose aryl ether bonds of lignin,
      promoted methane fermentation of softwood in the presence of wheat bran.

PMID- 16290244
TI  - Comparison of novel delivery systems for antisense peptide nucleic acids.
AB  - Peptide nucleic acids (PNAs) provide a powerful tool to study the mechanism of
      transcription and translation, an innovative strategy to regulate target gene
      expression. They have been successfully used in antisense technology, for their
      ability to specifically bind to messenger RNA (mRNA) targets and to inhibit
      translation of the target genes. However, unlike most of the DNA and RNA
      oligonucleotides, PNAs are poorly penetrated through the cell membrane, partially
      due to their uncharged property. To enhance the efficiency in PNA delivery, many
      strategies have been explored. We here compare the efficacy of three different
      delivery strategies for antisense PNA: 1) conjugation to hydrophobic peptides, 2)
      adsorption onto polymeric microspheres and 3) encapsulation in autologous
      erythrocytes. To this purpose, we designed and prepared PNA sequences able to
      inhibit the expression of macrophage enzymes involved in inflammatory process,
      i.e. nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) and tested their
      antisense activity in a murine macrophage cellular model. Both delivery through
      polymeric microspheres and encapsulation into erythrocytes allowed the antisense
      activity of unmodified PNAs at nanomolar concentration.

PMID- 16290245
TI  - Dermatan carriers for neovascular transport targeting, deep tumor penetration and
      improved therapy.
AB  - A new approach to functional tumor imaging and deep interstitial penetration of
      therapeutic agents is to target the upregulated transport activities of
      neovascular endothelium. Agents are formulated with the anionic
      glycosaminoglycan, 435-type dermatan sulfate (DS 435, 22.2 kDa), chemically
      enriched for oligosaccharide sequences that confer high heparin cofactor II
      binding and correlate with high tumor uptake. A magnetic resonance (MR) imaging
      agent is prepared as self-assembling, 5-nm nanoparticles of Fe(+3):deferoxamine
      (Fe:Df) bound by strong ion pairing to DS, which forms the outer molecular
      surface (Zeta potential -39 mV). On intravenous (i.v.) injection, Fe:Df-DS
      rapidly (<7 min) and selectively targets and transports at high capacity across
      the neovascular endothelium of large (2-cm) Dunning prostate R3327 AT1 rat
      tumors; releases from the abluminal surface, due to reversible binding of its
      multivalent, low-affinity (K(d) 10(-4) to 10(-5)) oligosaccharide ligands; and
      progressively penetrates the interstitium from its initial site of high uptake in
      the well-perfused outer tumor rim, into the poorly perfused central subregion. By
      gamma camera imaging of (67)Ga:Df-DS, the agent avoids normal site uptake and
      clears through the kidneys with a t(1/2) of 18 min. A therapeutic formulation of
      DS-doxorubicin (DS-dox) is prepared by aqueous high-pressure homogenization of
      the drug and DS 435, which produces 11-nm nanoparticles of doxorubicin cores
      coated with DS (Zeta potential -39 mV) that are stable to lyophilization.
      Microscopic analysis of tumor sections 3 h after i.v. injection shows much higher
      overall tumor fluorescence and deeper matrix penetration for DS-dox than
      conventional doxorubicin (dox): >75 vs. <25 microm between the nearest
      microvessels. DS-dox also results in enhanced tumor-cell internalization and
      nuclear localization of the drug. Therapeutic efficacies in established (250 +/-
      15 mg) MX-1 human breast tumor xenografts at maximum tolerated doses (MTDs) are
      (control vehicle, dox, dox-DS) (a) median days to 7-fold tumor growth: 8.3, 25.6
      (p = 0.0007), 43.2 (p = 0.0001); (b) complete 90-day tumor regressions: 0/10,
      0/10, 4/10. These results demonstrate the potential to develop a novel class of
      carbohydrate-targeted neovascular transport agents for sensitive, high-resolution
      (100-microm) MR imaging and improved treatment of larger sized human tumor
      metastases.

PMID- 16290246
TI  - The biology of exhaled nitric oxide (NO) in ischemia-reperfusion-induced lung
      injury: a tale of dynamism of NO production and consumption.
AB  - The main objective of this paper is to review the potential diagnostic roles of
      exhaled nitric oxide (NO) in evaluating ischemia-reperfusion-induced lung injury
      associated with cardiac surgery. We shall start by elaborating on current
      clinical practice of cardiac surgery and to arrive at the conclusion that
      clinically important ischemia-reperfusion injury is a common scenario of many
      forms of these surgical procedures. We shall conclude this part by establishing
      the clinical need for biomarkers of inflammation in cardiothoracic surgery and by
      proposing that exhaled NO could be an important new addition to our anaesthetic
      monitoring repertoire based on our expertise with exhaled breath monitoring. We
      shall then take a closer look at mechanisms of ischemia-reperfusion injury and
      will propose the role of reactive oxygen and nitrogen species as mediators and
      biomarkers of acute lung injury. This analysis will provide a good opportunity to
      highlight major potential mechanisms of altered NO production and bioactivity of
      NO. We shall conclude that multiple relevant mechanisms may either lead to
      increased production of NO or enhance consumption of NO, leaving us with the
      paradigm that NO maybe used either as a positive or negative biomarker of
      inflammation. In order to explore this dilemma further, we will investigate the
      predominant effect of oxidative stress on NO bioactivity in cell culture models
      of ischemia-reperfusion injury. We will then turn to animal models of ischemia
      reperfusion injury to elucidate the ultimate effects of this condition on lung NO
      production and concentrations of NO in the lung. Finally, we shall complete this
      journey by highlighting the human relevance of these observations by reviewing
      our own experience at Harefield Hospital, UK, and that of others, regarding
      exhaled NO in ischemia-reperfusion injury associated with cardiac surgery and
      lung transplantation.

PMID- 16290247
TI  - Should we screen for colorectal cancer in liver transplantation?

PMID- 16290243
TI  - The anatomy of decision support during inpatient care provider order entry
      (CPOE): empirical observations from a decade of CPOE experience at Vanderbilt.
AB  - The authors describe a pragmatic approach to the introduction of clinical
      decision support at the point of care, based on a decade of experience in
      developing and evolving Vanderbilt's inpatient "WizOrder" care provider order
      entry (CPOE) system. The inpatient care setting provides a unique opportunity to
      interject CPOE-based decision support features that restructure clinical
      workflows, deliver focused relevant educational materials, and influence how care
      is delivered to patients. From their empirical observations, the authors have
      developed a generic model for decision support within inpatient CPOE systems.
      They believe that the model's utility extends beyond Vanderbilt, because it is
      based on characteristics of end-user workflows and on decision support
      considerations that are common to a variety of inpatient settings and CPOE
      systems. The specific approach to implementing a given clinical decision support
      feature within a CPOE system should involve evaluation along three axes: what
      type of intervention to create (for which the authors describe 4 general
      categories); when to introduce the intervention into the user's workflow (for
      which the authors present 7 categories), and how disruptive, during use of the
      system, the intervention might be to end-users' workflows (for which the authors
      describe 6 categories). Framing decision support in this manner may help both
      developers and clinical end-users plan future alterations to their systems when
      needs for new decision support features arise.

PMID- 16290248
TI  - Locations of mouse DNA damage response and repair loci, and cancer risk
      modifiers.
AB  - An outline is presented of an electronically accessible database that compares
      the locations of mouse genes involved in DNA repair, apoptosis, cell cycle and
      signal transduction with those of known cancer risk modifier genes. The database
      has a primary but not exclusive focus on modifiers of ionizing radiation (IR)
      cancer risk and genes involved in IR-induced DNA damage responses. The database
      () provides a useful tool for assessing the role of DNA damage response genes in
      cancer predisposition.

PMID- 16290250
TI  - The biology of intron gain and loss.
AB  - Intron density in eukaryote genomes varies by more than three orders of
      magnitude, so there must have been extensive intron gain and/or intron loss
      during evolution. A favored and partial explanation for this range of intron
      densities has been that introns have accumulated stochastically in large
      eukaryote genomes during their evolution from an intron-poor ancestor. However,
      recent studies have shown that some eukaryotes lost many introns, whereas others
      accumulated and/or gained many introns. In this article, we discuss the growing
      evidence that these differences are subject to selection acting on introns
      depending on the biology of the organism and the gene involved.

PMID- 16290249
TI  - Alkylpurine-DNA-N-glycosylase excision of 7-(hydroxymethyl)-1,N6-ethenoadenine, a
      glycidaldehyde-derived DNA adduct.
AB  - Glycidaldehyde (GDA) is a bifunctional alkylating agent that has been shown to be
      mutagenic in vitro and carcinogenic in rodents. However, the molecular mechanism
      by which it exerts these effects is not established. GDA is capable of forming
      exocyclic hydroxymethyl-substituted etheno adducts on base residues in vitro. One
      of them, 7-(hydroxymethyl)-1,N6-ethenoadenine (7-hm-epsilonA), was identified as
      the principal adduct in mouse skin treated with GDA or a glycidyl ether. In this
      work, using defined oligonucleotides containing a site-specific 7-hm-epsilonA,
      the human and mouse alkylpurine-DNA-N-glycosylases (APNGs), responsible for the
      removal of the analogous 1,N6-ethenoadenine (epsilonA) adduct, are shown to
      recognize and excise 7-hm-epsilonA. Such an activity can be significantly
      modulated by both 5' neighboring and opposite sequence contexts. The efficiency
      of human or mouse APNG for excision of 7-hm-epsilonA is about half that, or
      similar to the excision of epsilonA, respectively. When human or mouse cell-free
      extracts were tested, however, the extent of 7-hm-epsilonA excision is
      dramatically lower than that for epsilonA, suggesting that, in the crude
      extracts, the APNG activities toward these two adducts are differentially
      affected. Using cell-free extracts from APNG deficient mice, this enzyme is shown
      to be the primary glycosylase excising 7-hm-epsilonA. A structural approach,
      using molecular modeling, was employed to examine how the structure of the 7-hm
      epsilonA adduct affects DNA conformation, as compared to the epsilonA adduct.
      These novel substrate specificities could have both biological and structural
      implications.

PMID- 16290251
TI  - Determination of free ertapenem in plasma and bronchoalveolar lavage by high
      performance liquid chromatography with ultraviolet detection.
AB  - A sensitive assay for the determination of unbound ertapenem in human plasma and
      bronchoalveolar lavage (BAL) was developed using ultrafiltration of plasma and
      BAL samples. A rapid HPLC method was used with ultraviolet detection set at a
      wavelength of 305 nm and a separation on a Prontosil AQ C18 column, with imipenem
      used as internal standard. This assay was linear over the concentration range of
      0.5-100 microg/mL and 0.25-50 microg/mL in plasma and BAL, respectively. Limits
      of detection and quantitation were respectively 0.05 and 0.25 microg/mL.
      Validation data for accuracy and precision were CV<2.48 and 8.25%, accuracy in
      the range 98.1-104.2% and 102.2-108.4%, respectively, for intra and inter-day.

PMID- 16290252
TI  - Scutellariae radix extracts suppress ethanol-induced caspase-11 expression and
      cell death in N(2)a cells.
AB  - Scutellariae radix is a Chinese herbal medicine that has been used to treat
      disease conditions accompanying inflammation and oxidative stress. In the present
      study, we examined the effect of Scutellariae radix extracts during acute ethanol
      exposure in N(2)a neuroblastoma. The Scutellariae radix extracts effectively
      inhibited ethanol-induced apoptosis and caspase-3/-7 activation. Ethanol induced
      the expression of caspase-11 that has been known as a dual regulator of
      pathological apoptosis and inflammatory response. The ethanol-induced caspase-11
      expression was suppressed by pretreatment of the Scutellariae radix extracts.
      Furthermore, the activation of caspase-3/-7 and apoptosis were significantly
      inhibited in caspase-11-/- mouse embryonic fibroblasts following ethanol
      treatment. These results suggest that caspase-11 has a regulatory role in ethanol
      induced apoptosis, and the suppression of caspase-11 may be a mechanism by which
      Scutellariae radix exerts its cytoprotective effect.

PMID- 16290253
TI  - Molecular characterization of a novel dipeptidyl peptidase like 2-short form
      (DPL2-s) that is highly expressed in the brain and lacks dipeptidyl peptidase
      activity.
AB  - DPL2 (DPP10) found at chromosome 2q14.1 is a member of the dipeptidyl peptidase
      IV (DPIV) gene family. Here we characterize a novel short DPL2 isoform (DPL2-s),
      a 789-amino acid protein, that differs from the previously described long DPL2
      isoform (DPL2-l) at the N-terminal cytoplasmic domain by 13 amino acids. The two
      DPL2 isoforms use alternate first exons. DPL2 mRNA was expressed mainly in the
      brain and pancreas. Multiple forms of recombinant DPL2-s protein were observed in
      293T cells, having mobilities 96 kDa, 100 kDa, and approximately 250 kDa which
      may represent soluble DPL2, transmembrane DPL2 and multimeric DPL2 respectively.
      DPL2 is glycosylated as a band shift is observed following PNGase F
      deglycosylation. DPL2-s was expressed primarily on the cell surface of
      transfected 293T and PC12 cells. DPL2-s exhibits high sequence homology with
      other DPIV peptidases, but lacks a catalytic serine residue and lacks dipeptidyl
      peptidase activity. Substitutions of Gly(644)-->Ser, Lys(643)Gly(644)-->TrpSer,
      or Asp(561)Lys(643)Gly(644)-->TyrTrpSer in the catalytic motif did not confer
      dipeptidyl peptidase activity upon DPL2-s. Thus, although DPL2 is similar in
      structure and sequence to the other dipeptidyl peptidases, it lacks vital
      residues required to confer dipeptidyl peptidase activity and has instead evolved
      features that enable it to act as an important component of voltage-gated
      potassium channels.

PMID- 16290254
TI  - Targeted drug delivery with dendrimers: comparison of the release kinetics of
      covalently conjugated drug and non-covalent drug inclusion complex.
AB  - Dendrimers have unique characteristics including monodispersity and modifiable
      surface functionality, along with highly defined size and structure. This makes
      these polymers attractive candidates as carriers in drug delivery applications.
      Drug delivery can be achieved by coupling a drug to polymer through one of two
      approaches. Hydrophobic drugs can be complexed within the hydrophobic dendrimer
      interior to make them water-soluble or drugs can be covalently coupled onto the
      surface of the dendrimer. Using both methods we compared the efficacy of
      generation 5 PAMAM dendrimers in the targeted drug delivery of methotrexate
      coupled to the polymer. The amine-terminated dendrimers bind to negatively
      charged membranes of cells in a non-specific manner and can cause toxicity in
      vitro and in vivo. To reduce toxicity and to increase aqueous solubility,
      modifications were made to the surface hydroxyl groups of the dendrimers. For
      targeted drug delivery, the dendrimer was modified to have a neutral terminal
      functionality for use with surface-conjugated folic acid as the targeting agent.
      The complexation of methotrexate within a dendrimer changes the water insoluble
      drug into a stable and readily water-soluble compound. When this dendrimer
      complexed drug, however, was placed in a solution of phosphate buffered saline,
      the methotrexate was immediately released and displayed diffusion characteristics
      identical to free methotrexate. Covalently coupled methotrexate dendrimer
      conjugates were stable under identical conditions in water and buffered saline.
      Cytotoxicity tests showed that methotrexate as the dendrimer inclusion complex
      had an activity identical to the free drug in vitro. In contrast, folic acid
      targeted dendrimer with covalently conjugated methotrexate specifically killed
      receptor-expressing cells by intracellular delivery of the drug through receptor
      mediated endocytosis. This study demonstrates that while drug as a dendrimer
      inclusion complex is readily released and active in vitro, covalently conjugated
      drug to dendrimer is better suited for specifically targeted drug delivery.

PMID- 16290255
TI  - Mice lacking thrombospondin 2 show an atypical pattern of endocortical and
      periosteal bone formation in response to mechanical loading.
AB  - Thrombospondin 2 (TSP2) is an extracellular matrix (ECM) protein localized to
      bone. Since mice with a targeted disruption of the TSP2 gene (TSP2-null) have
      increased bone formation, we hypothesized that mice lacking TSP2 would show an
      enhanced osteogenic response to mechanical loading. We addressed our hypothesis
      by subjecting wild-type (WT) and TSP2-null mice to mechanical loading using the
      non-invasive murine tibia loading device, and statistical comparisons were made
      between loaded and unloaded bones within genotype, between genotypes, and between
      the periosteal and endocortical surfaces within genotype. Right tibiae of WT and
      TSP2-null mice received 5 days of a low-magnitude loading protocol. This low
      magnitude loading (inducing approximately 900 and 500 muepsilon at periosteal and
      endocortical surfaces of WT bones, respectively) affected neither periosteal nor
      endocortical bone formation rate (BFR/BS) when comparing loaded to intact bones
      in either WT or TSP2-null mice, nor did it result in any significant differences
      between WT and TSP2-null. As well, there was no difference between loaded
      endocortical and periosteal surfaces in WT mice; however, endocortical BFR/BS in
      TSP2-null loaded tibia was significantly elevated relative to the periosteal
      BFR/BS-despite peak periosteal strains being significantly greater than
      endocortical strains in TSP2-null mice (690 versus 460 muepsilon). To confirm
      this counterintuitive surface-specific response in TSP2-null mice and to induce
      significant periosteal bone formation, osteogenic potency of the loading protocol
      was amplified by doubling the number of loading bouts (10 loading days) and
      loading magnitude (1 Hz, resulting in 1400 and 900 muepsilon peak strain at the
      periosteal and endocortical surfaces, respectively). Under load, both WT and TSP2
      null mice showed significantly increased periosteal mineralizing surface (by
      nearly three-fold and five-fold, respectively), but mineral apposition rate (MAR)
      was not statistically changed. The increased MS/BS resulted in a five-fold
      increase in WT periosteal BFR/BS, but the TSP2-null periosteal BFR/BS was
      unchanged. Furthermore, this increase in WT loaded periosteal BFR/BS was
      statistically greater than the WT endocortical BFR/BS. At the endocortical
      surface of WT mice, loading did not significantly increase bone formation
      parameters (versus intact). In contrast, at the endocortical surface of TSP2-null
      mice, loading induced a significant two-fold increase in BFR/BS (versus intact),
      that was also significantly greater than the endocortical BFR/BS of loaded WT
      mice. Thus, exogenous loading of TSP2-null mice resulted in highly variable
      responses that did not reflect the induced strains at the periosteal and
      endocortical surfaces. While in WT mice, loading resulted in increased periosteal
      BFR/BS that was greater than the endocortical BFR/BS, in TSP2-null mice loading
      resulted in endocortical (not periosteal) BFR/BS that was elevated. This reversal
      in envelope-specific bone formation in TSP2-null mice occurred despite periosteal
      strains being significantly greater than endocortical (1290 versus 775 muepsilon)
      and strain distributions being similar to that of WT. These results show that the
      disruption of a single gene can lead to a reversal in normal pattern of load
      induced bone formation, and more specifically, that the functional interaction of
      TSP2 with mechanical loading is highly contextual and specific to the cortical
      bone envelope examined.

PMID- 16290256
TI  - Skin rash and bronchoalveolar histology correlates with clinical benefit in
      patients treated with gefitinib as a therapy for previously treated advanced or
      metastatic non-small cell lung cancer.
AB  - BACKGROUND: Only 15% of patients with non-small cell lung cancer (NSCLC) treated
      with oral epidermal growth factor tyrosine kinase inhibitor gefitinib, as a
      second-line therapy have objective responses. Fifty percent will have improvement
      of lung cancer related symptoms. It will be critical to identify patients who
      will benefit clinically from this therapy even when there is no objective
      response seen on imaging studies. We have performed a retrospective analysis of
      76 patients who received gefitinib as a therapy for previously treated metastatic
      NSCLC at the University of Minnesota Comprehensive Cancer Center in order to
      describe characteristics of patients who will likely derive benefits from
      gefitinib therapy. METHODS: All patients treated with gefitinib therapy at the
      University of Minnesota from September 2001 to January 2004 were entered into the
      study. The Log-rank Test and Cox proportional hazards regression were used to
      assess the effect of the number of previous therapy lines, histology subtype,
      performance status, gender, stage of disease at initial diagnosis, and presence
      of skin rash on time to disease progression and overall survival (OS). Fisher's
      Exact Test and multiple logistic regressions were used to assess the effect of
      these covariates on disease response. RESULTS: Seventy-six patients entered the
      study, with a median age of 60 years (range 37-82). There were 37 female and 39
      male patients; 47 patients had adenocarcinoma, 22 had squamous and 7 had other
      NSCLC histologies. Six patients had no prior therapy, 23 had one, 32 had two, 8
      had three, and 7 had four prior therapies for lung cancer. Fifty-six were current
      smokers. Median time to disease progression was 3 months (95% CI: 3.0, 6.0).
      There was no difference in time to disease progression whether patients had one
      or more prior therapies. Patients with brain metastases (26 patients) benefited
      from gefitinib therapy at least equally well as those without brain metastatic
      disease. Patients with adenocarcinoma histology with bronchoalveolar features had
      superior median time to progression versus other lung cancer histology (14 months
      versus 3 months, p=0.076), which translated into survival advantage in this group
      >24 months (95% CI: 0.76, 24+) versus 6.6 months (p=0.0096). Patients with EGFR
      positive tumors had median survival of 10.2 months (95% CI: 1.45, 16.94) versus
      3.7 months (95% CI: 2.66, 4.74) with EGFR negative tumors. Patients who developed
      any degree of skin rash had prolonged time to disease progression with median of
      6 months (95% CI: 2.56, 15.5) versus patients without skin rash median 3 months
      (95% CI: 1.43, 2.83) (p=0.023). This last factor was the best predictor of
      improved time to disease progression in multiple regression analysis (p=0.0405).
      CONCLUSION: A subgroup of patients with NSCLC will benefit from gefitinib
      therapy. Objective responses will likely be seen in half the patients with
      mutation of internal domain of EGFR; however, a larger group of patients will
      also enjoy prolonged disease stabilization and clinical benefit. We suggest that
      adenocarcinoma with bronchoalveolar features and the presence of skin rash may be
      used as predictors of gefitinib benefit.

PMID- 16290257
TI  - Superovulation and embryo transfer in Bos indicus cattle.
AB  - Compared to Bos taurus breeds, Bos indicus breeds of cattle present several
      differences in reproductive physiology. Follicular diameter at deviation and at
      the time of ovulatory capability are smaller in B. indicus breeds. Furthermore,
      B. indicus breeds have a greater sensitivity to gonadotropins, a shorter duration
      of estrus, and more often express estrus during the night. These differences must
      be considered when setting up embryo transfer programs for B. indicus cattle. In
      recent studies, we evaluated follicular dynamics and superovulatory responses in
      B. indicus donors with the objective of implementing fixed-time AI protocols in
      superstimulated donors. Protocols using estradiol and progesterone/progestrogen
      releasing devices to control follicular wave emergence were as efficacious as in
      B. taurus cattle, allowing the initiation of superstimulatory treatments (with
      lower dosages of FSH than in B. taurus donors) at a self-appointed time.
      Furthermore, results presented herein indicate that delaying the removal of
      progesterone/progestogen-releasing devices, combined with the administration of
      GnRH or pLH 12 h after the last FSH injection, results in synchronous ovulations,
      permitting the application of fixed-time AI of donors without the necessity of
      estrus detection and without compromising the results.

PMID- 16290258
TI  - Changes in reproductive physiology of lactating dairy cows due to elevated
      steroid metabolism.
AB  - This manuscript focuses on potential changes in reproductive physiology that
      occur due to high milk production in lactating dairy cows. Four reproductive
      measures are discussed: interval to first ovulation, conception rate, duration of
      estrus, and multiple ovulation rate. The last two responses have now been closely
      linked to level of milk production. In contrast, time to first ovulation does not
      appear to be associated with level of milk production, and the association of
      conception rate with level of milk production is still controversial. In an
      attempt to explain some of the changes in reproductive physiology caused by high
      milk production a model of elevated steroid metabolism in lactating dairy cows is
      presented. Although many aspects of this model remain to be tested, a central
      role for elevated steroid metabolism in lactation-induced reproductive changes
      seems likely.

PMID- 16290259
TI  - Factors potentially affecting fertility of lactating dairy cow recipients.
AB  - Objectives of this study were to evaluate factors that could affect pregnancy
      rate after embryo transfer (ET) in lactating dairy cow recipients. The trial was
      conducted at a dairy farm located in Descalvado, SP, Brazil from October 2003 to
      September 2004. From 1037 cows with CL that were treated with an injection of
      PGF2alpha, 43.3% were detected in heat; 263 were previously assigned at day of
      PGF2alpha injection for AI and 186 for ET. Ovulation rate was 85.7% (385/449).
      Pregnancy rate for cows with CL for AI and embryo transfer recipients were 36.5%
      (84/230) and 58.7% (91/155) at day 25 and 33.0% (76/230) and 45.8% (71/155) at
      day 46, respectively. Embryonic loss were 9.5% (8/84) for the AI group and 21.9%
      (20/91) for the ET group. Average milk production was 31.4 L/day/cow. Average
      daily milk production from 7 days before PGF2alpha injection to 7 days after ET
      tended (P < 0.10) to influence pregnancy rate on days 25 and 46. Average daily
      milk production from the day of embryo transfer to 7 days after influenced
      embryonic loss (P < 0.05). Cows with higher milk production had lower probability
      of pregnancy and higher probability of embryonic loss. Cows with higher days in
      milk had higher probability of pregnancy. Cows with higher rectal body
      temperature had lower probability of pregnancy and higher probability of
      embryonic loss. The influence of high milk yield and body temperature on
      fertility in lactating dairy cow recipients suggests that these effects can occur
      also after embryo reaches the blastocyst stage.

PMID- 16290260
TI  - Identification and characterization of binding sites for human urotensin-II in
      Sprague-Dawley rat renal medulla using quantitative receptor autoradiography.
AB  - Urotensin-II (U-II), a ligand for the G-protein-coupled receptor UT, has been
      characterized as the most potent mammalian vasoconstrictor identified to date.
      Although circulating levels of U-II are altered in lower species (e.g., fish)
      upon exposure to hypo-osmotic stress, little is known about the actions of this
      cyclic undecapeptide within the kidney, an organ that plays a pivotal role in the
      control of cardiovascular homeostasis, influencing both cardiac preload (plasma
      volume) and after load (peripheral resistance). The present study reports the
      identification of specific, high affinity [125I]hU-II binding sites in Sprague
      Dawley rat kidney outer medulla by autoradiography and also through membrane
      radioligand binding (Kd 1.9 +/- 0.9 nM and Bmax 408 +/- 47 amol mm(-2) and Kd 1.4
      +/- 0.3 nM and Bmax 51.3 +/- 7.8 fmol mg(-1) protein, respectively). Differences
      were observed in the binding characteristics within rat strains. Compared to the
      Sprague-Dawley, Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rat
      kidney outer medulla displayed low density < 20 fmol mg(-1) protein and low
      affinity (> 1 microM) [125I]hU-II binding sites. Thus, the relative contribution
      of specific U-II binding sites to the physiological actions of U-II in the
      control of cardiorenal homeostasis is worthy of further investigation.

PMID- 16290261
TI  - An fMRI investigation of the neural correlates underlying the processing of novel
      metaphoric expressions.
AB  - The neural networks associated with processing related pairs of words forming
      literal, novel, and conventional metaphorical expressions and unrelated pairs of
      words were studied in a group of 15 normal adults using fMRI. Subjects read the
      four types of linguistic expressions and decided which relation exists between
      the two words (metaphoric, literal, or unrelated). According to the Graded
      Salience Hypothesis (GSH, ), which predicts a selective RH involvement in the
      processing of novel, nonsalient meanings, it is primarily the degree of meaning
      salience of a linguistic expression rather than literality or nonliterality,
      which modulates the degree of left hemisphere (LH) and right hemisphere (RH)
      processing of metaphors. In the present study, novel metaphorical expressions
      represented the nonsalient interpretations, whereas conventional metaphors and
      literal expressions represented the salient interpretations. A direct comparison
      of the novel metaphors vs. the conventional metaphors revealed significantly
      stronger activity in right posterior superior temporal sulcus, right inferior
      frontal gyrus, and left middle frontal gyrus. These results support the GSH and
      suggest a special role for the RH in processing novel metaphors. Furthermore, the
      right PSTS may be selectively involved in verbal creativity.

PMID- 16290262
TI  - Noun and verb processing in Greek-English bilingual individuals with anomic
      aphasia and the effect of instrumentality and verb-noun name relation.
AB  - Noun and verb comprehension and production was investigated in two groups of late
      bilingual, Greek-English speakers: individuals with anomic aphasia and a control
      group of non-brain injured individuals matched for age and gender. There were no
      significant differences in verb or noun comprehension between the two groups in
      either language. However, verb and noun production during picture naming was
      significantly worse in the bilingual individuals with anomic aphasia in both
      languages, who also showed a specific verb impairment in Greek and English. The
      potential underlying level of breakdown of the specific verb impairment was
      further investigation with reference to two specific features of verbs:
      instrumentality and verb-noun relationship. Additional results revealed a
      facilitatory effect of Instrumentality in both languages. However, there was no
      effect of verb-noun name relation in Greek, and a negative effect of verb-noun
      name relation was observed in English. Lemma retrieval seemed to be intact in
      this group of bilingual individuals whose main problem seemed to arise during the
      retrieval of the phonological representation of the target word. This impairment
      was greater in English. The findings are discussed in terms of three current
      models of word production.

PMID- 16290263
TI  - Involvement of glutamate receptors of the NMDA type in the modulation of
      acetylcholine and glutamate overflow from the guinea pig ileum during in vitro
      hypoxia and hypoglycaemia.
AB  - The involvement of NMDA glutamate receptors in the effects of glucose/oxygen
      deprivation (in vitro ischaemia) on spontaneous endogenous acetylcholine and
      glutamate overflow from the guinea pig ileum was studied. Neurotransmitter
      overflow was measured by HPLC. Deprivation of glucose in the medium slightly
      reduced acetylcholine overflow, and did not significantly influence glutamate
      overflow. During oxygen deprivation and glucose/oxygen deprivation, acetylcholine
      overflow augmented with a biphasic modality: an early peak was followed by a long
      lasting increase, whereas glutamate overflow increased with a rapid and sustained
      modality. The effects of glucose/oxygen deprivation on both acetylcholine and
      glutamate overflow were abolished after reperfusion with normal oxygenated
      medium. Acetylcholine and glutamate overflow induced by glucose/oxygen
      deprivation were significantly reduced in the absence of external Ca(2+) as well
      as by the addition of the mitochondrial Na(+)-Ca(2+) exchanger blocker, CGP
      37157, and of the endoplasmic reticulum Ca(2+)/ATPase blocker, thapsigargin. +/
      AP5, an NMDA receptor antagonist, and 5,7-diCl-kynurenic acid, an antagonist of
      the glycine site associated to NMDA receptor, markedly depressed glucose/oxygen
      deprivation-induced acetylcholine and glutamate overflow as well. Our results
      suggest that in vitro simulated ischaemia evokes acetylcholine and glutamate
      overflow from the guinea pig ileum, which is partly linked to an increase in
      intracellular Ca(2+) concentration dependent on both Ca(2+) influx from the
      extracellular space and Ca(2+) mobilization from the endoplasmic reticulum and
      mitochondrial stores. During glucose/oxygen deprivation, ionotropic glutamate
      receptors of the NMDA type exert both a positive feedback modulation of glutamate
      output and contribute to increased acetylcholine overflow.

PMID- 16290264
TI  - Dopamine D1 receptor-mediated toxicity in human SK-N-MC neuroblastoma cells.
AB  - Striatal degeneration occurs through unknown mechanisms in certain
      neurodegenerative disorders characterized by increased and sustained synaptic
      levels of dopamine. In the present studies, we examined the effects of treatment
      of SK-N-MC neuroblastoma cells with dopamine to understand the participation of
      dopamine D(1) receptor in postsynaptic cytotoxicity. Treatment of SK-N-MC cells
      either with dopamine or the D(1) receptor agonist SKF R-38393 resulted in a
      significant increase in the production of reactive oxygen species (by
      approximately 2.75-fold) and cell death ( approximately 50%), while antagonism of
      the D(1) receptor with SCH 23390 significantly reversed (to approximately 75% of
      control level) these effects. Accumulation of cAMP in dopamine treated cells
      (t(1/2)=1.5h) preceded changes in ionic gradient (t(1/2)=6.5h), as measured by
      intracellular potassium concentration and leakage of cytochrome c into the
      cytosol (t(1/2)=13 h), suggesting a possible staging of toxic events as a result
      of activation of D(1) receptor by dopamine. Examination of cellular metabolic
      properties with (13)C NMR spectroscopy showed an inhibitory effect on
      tricarboxylic acid cycle metabolism via D(1)-mediated receptors after treatment
      with dopamine, suggesting a direct role for D(1) receptor in dopamine-induced
      postsynaptic cell death. The present studies provide novel insight into a
      possible patho-physiological staging of cytotoxic events that are mediated by
      activation of D(1) receptor.

PMID- 16290265
TI  - Effect of coenzyme Q10 and vitamin E on brain energy metabolism in the animal
      model of Huntington's disease.
AB  - The neuropathological and clinical symptoms of Huntington's disease (HD) can be
      simulated in animal model with systemic administration of 3-nitropropionic acid
      (3-NP). Energy defects in HD could be ameliorated by administration of coenzyme
      Q(10) (CoQ(10)), creatine, or nicotinamid. We studied the activity of creatine
      kinase (CK) and the function of mitochondrial respiratory chain in the brain of
      aged rats administered with 3-NP with and without previous application of
      antioxidants CoQ(10)+vitamin E. We used dynamic and steady-state methods of in
      vivo phosphorus magnetic resonance spectroscopy ((31)P MRS) for determination of
      the pseudo-first order rate constant (k(for)) of the forward CK reaction, the
      phosphocreatine (PCr) to adenosinetriphosphate (ATP) ratio, intracellular pH(i)
      and Mg(i)(2+) content in the brain. The respiratory chain function of isolated
      mitochondria was assessed polarographically; the concentration of CoQ(10) and
      alpha-tocopherol by HPLC. We found significant elevation of k(for) in brains of 3
      NP rats, reflecting increased rate of CK reaction in cytosol. The function of
      respiratory chain in the presence of succinate was severely diminished. The
      activity of cytochromeoxidase and mitochondrial concentration of CoQ(10) was
      unaltered; tissue content of CoQ(10) was decreased in 3-NP rats. Antioxidants
      CoQ(10)+vitamin E prevented increase of k(for) and the decrease of CoQ(10)
      content in brain tissue, but were ineffective to prevent the decline of
      respiratory chain function. We suppose that increased activity of CK system could
      be compensatory to decreased mitochondrial ATP production, and CoQ(10)+vitamin E
      could prevent the increase of k(for) after 3-NP treatment likely by activity of
      CoQ(10) outside the mitochondria. Results of our experiments contributed to
      elucidation of mechanism of beneficial effect of CoQ(10) administration in HD and
      showed that the rate constant of CK is a sensitive indicator of brain energy
      disorder reflecting therapeutic effect of drugs that could be used as a new in
      vivo biomarker of neurodegenerative diseases.

PMID- 16290266
TI  - Regional and temporal alterations of ODC/polyamine system during ALS-like
      neurodegenerative motor syndrome in G93A transgenic mice.
AB  - Natural polyamines (putrescine, spermidine and spermine) are ubiquitous molecules
      known to regulate a number of physiological processes and suspected to play a
      role also in various pathological conditions. Changes in polyamine levels and in
      their biosynthetic enzymes have been described for some neurodegenerative
      diseases but the available data are incomplete and somewhat contradictory. We
      report here alterations of the key enzyme of the polyamine pathway, ornithine
      decarboxylase (ODC) catalytic activity and polyamine levels in different CNS
      areas from SOD1 G39A transgenic mice, an animal model for amyotrophic lateral
      sclerosis (ALS). ODC catalytic activity, was found significantly increased both
      in the cervical and lumbar spinal cord and, to a lesser extent in the brain stem
      of transgenic mice at a symptomatic stage of the disease (125-day-old mice),
      while no differences were present at a pre-symptomatic stage (55-day-old mice).
      In parallel with the increase of ODC activity putrescine levels were several
      times increased in both cervical and lumbar spinal cord and in the brain stem of
      125-day-old SOD1 G39A mice. Higher order polyamines were not increased except for
      a significant increase of spermidine in the cervical spinal cord. The present
      data demonstrate considerable alterations of the ODC/polyamine system in a
      reliable animal model of ASL, consistent with their role in neurodegeneration and
      in particular in motor neuron diseases.

PMID- 16290267
TI  - Inhibition of Notch signaling enhances tissue repair in an animal model of
      multiple sclerosis.
AB  - Oligodendrocytes (OLs) fail to regenerate myelin destroyed by the immune attack
      in multiple sclerosis (MS) and lesion areas are eventually largely occupied by
      astrocytic scar tissue. Loss of OLs in MS does not account for the limited myelin
      repair as lesions contain a considerable number of OL precursor cells (OPC).
      Activation of the Notch pathway has been shown to provide inhibitory signals for
      OPC and to hamper their ability to produce myelin during CNS development. Here we
      show that gamma-secretase inhibition of Notch signaling within OL of CNS of SJL/J
      mice with experimental autoimmune encephalomyelitis (EAE) significantly enhanced
      clinical recovery and in the CNS, promoted remyelination and reduced axonal
      damage. Functional assays confirmed decreased Notch signaling in inhibitor
      treated groups. Therefore, gamma-secretase inhibition led to an environment more
      conducive to myelin repair and axonal survival. Our results suggest that
      manipulation of the environment associated with Notch activation in the mature
      CNS provides a promising therapeutic target in MS.

PMID- 16290268
TI  - Magnetization transfer imaging of gray and white matter in mild cognitive
      impairment and Alzheimer's disease.
AB  - OBJECTIVE: To assess whether structural brain damage as detected by magnetization
      transfer imaging (MTI) in Alzheimer's disease (AD) and mild cognitive impairment
      (MCI) is located in the gray matter (GM) and/or the white matter (WM). METHODS:
      Fifty-five AD patients, 19 MCI patients and 43 subjects with normal cognitive
      function participated in this study. GM and WM segmentations were generated from
      dual fast spin-echo MR images. These masks were co-registrated to MT images for
      volumetric MTI-analysis of the GM and WM. RESULTS: AD patients had a lower GM
      volume than controls. Both MCI and AD patients had more structural brain damage
      in both GM and WM than subjects with normal cognition. Cerebral lesion load in
      both GM and WM was associated with the degree of cognitive impairment.
      CONCLUSION: Using MTI, structural brain changes that are related to cognitive
      impairment could be demonstrated in both GM and WM of patients with AD and MCI.
      These results suggest that cerebral changes are present in GM and WM even before
      patients are clinically demented.

PMID- 16290269
TI  - Metabolism, mood and cognition in aging: the importance of lifestyle and dietary
      intervention.
AB  - We are witnessing an unprecedented rise in obesity and Type 2 diabetes. Until
      recently, study of the relation between metabolic dysregulation and higher brain
      function was limited. This paper summarizes the findings of a Spark workshop that
      focussed on the impact of obesity and diabetes on mood and cognition.
      Disturbances in peripheral glucose regulation are associated with cognitive
      impairment and depressed mood, especially in older adults. Multiple mechanisms
      and mediators underlie this association including insulin, glucose, neurotropic
      factors, glucocorticoids, inflammatory agents and reactive oxygen species.
      Importantly, prevention and even reversal of diabetes and obesity related
      cognitive impairment and depressive mood can be brought about by lifestyle
      modification. In particular, increasing physical fitness and moderating/changing
      food intake will have beneficial effects. Prevention of obesity and hyperglycemia
      by adopting a healthy lifestyle will contribute to the maintenance of functional
      integrity and mental health later in life.

PMID- 16290270
TI  - Peripheral clearance of amyloid beta peptide by complement C3-dependent adherence
      to erythrocytes.
AB  - Brain deposits of amyloid beta peptide (Abeta) have been a diagnostic hallmark of
      Alzheimer's disease (AD) for nearly a century. Recent studies have demonstrated
      that Abeta is also present in peripheral blood. Here, we present evidence that
      circulating Abeta42 is subject to complement C3b-dependent adherence to
      complement receptor 1 (CR1) on erythrocytes, a classical set of mechanisms by
      which pathogens and proteins recognized as foreign are cleared from the
      bloodstream. Levels of Abeta42 targeted by this pathway differ significantly in
      AD compared to mild cognitive impairment and nondemented elderly controls.

PMID- 16290271
TI  - The use of buccal smears for a non-invasive screening of the 35delG mutation of
      the Connexin-26 gene in hearing impaired young children.
AB  - OBJECTIVES: Recent advances in genetic research indicate that about 50% of
      congenital deaf patients have a genetic background, with mutations in the
      Connexin-26 gene being the most frequent one. Screening methods for the genetic
      cause of deafness have so far mostly been based on the use of peripheral whole
      blood as DNA source. The use of buccal smears for the genetic screening of deaf
      patients presents an interesting alternative to drawing blood, especially in
      young children. In order to validate this method, we compared results from buccal
      smears from very young deaf children (age<or=3 years) and deaf patients older
      than 3 years with the results from blood samples deriving from the same patients.
      METHODS: The detection of the 35delG mutation in the Connexin-26 gene was chosen
      to demonstrate the method's feasibility. Blood and buccal smears were collected
      for genetic analysis from 29 very young deaf children (Group 1: age<or=3 years)
      and 31 deaf patients older than 3 years (Group 2) during their clinical pre
      evaluation for cochlear implantation. Genomic DNA was isolated from blood as well
      as from buccal smears. Yield of both sources was determined by photometric
      evaluation of the isolated DNA concentration. Genomic DNA isolated from blood and
      buccal smears was then submitted to PCR-mediated site-directed mutagenesis
      followed by BS1 YI restriction and electrophoresis. The results for 35delG
      detection in DNA originating from blood were compared to those of buccal smears.
      RESULTS: Quantitative DNA analysis showed that both sources provided adequate
      amounts of DNA for PCR. No significant difference was found between Group 1 and
      Group 2 considering either the DNA amount isolated from blood or from buccal
      smears. In all 60 patients, DNA isolated from blood revealed the same results
      concerning the presence of the 35delG mutation as DNA originating from buccal
      smears. CONCLUSIONS: This study demonstrates that buccal smears are an adequate,
      reliable source of genomic DNA providing material for genetic tests that can
      especially help to avoid drawing blood from very young children for the genetic
      screening of deafness.

PMID- 16290272
TI  - Foodstuffs and colorectal cancer risk: a review.
AB  - BACKGROUND AND AIMS: To assess the relationships between food intake and
      colorectal cancer risk. METHODS: Systematic review of available prospective
      studies on dietary intake and colorectal cancer. RESULTS: Twelve out of 15
      studies found no significant relationship between vegetable intake and colorectal
      cancer risk; also, 11 out of 14 studies found no relationship with fruit
      consumption. Conversely, the combined consumption of vegetables and fruit reduced
      colorectal cancer risk in three out of six studies, although the relationship was
      somewhat inconsistent between genders and anatomical localizations. Most studies
      found no relationship between cancer risk and red meat (15 in 20) or processed
      meat (seven out of 11) consumption; still, most of the reported relative risks
      were above unity, suggesting that high consumption of red or processed meat might
      increase colorectal cancer risk. The consumption of white meat, fish/seafood,
      dairy products, coffee or tea was mostly unrelated to colorectal cancer risk,
      although the consumption of smoked or salted fish actually increased risk.
      CONCLUSIONS: The relationships between dietary intake and colorectal cancer risk
      might be less important than previously reported. The combined consumption of
      vegetables and fruit might be protective, whereas excessive consumption of meat
      or smoked/salted/processed food appears to be deleterious.

PMID- 16290274
TI  - Mechanisms of odor discrimination: neurophysiological and behavioral approaches.
AB  - Understanding how complex neuronal circuits in the brain perform advanced
      computations is a central question in neuroscience that can only be addressed
      using a combination of approaches, including neurophysiology and behavioral
      analyses. In the olfactory bulb, neurophysiological studies have revealed that
      neuronal interactions reorganize odor-evoked activity patterns so that their
      discriminability is enhanced. Recent behavioral studies have examined the role of
      this computation in odor discrimination tasks and generated working models of
      behavioral odor discrimination strategies. The results appear consistent with a
      role of pattern reorganization in odor discrimination behavior but further
      studies are necessary to resolve this issue. These studies advance the
      understanding of neuronal circuit function in the olfactory bulb and illustrate
      benefits and caveats of comparing behavioral and neurophysiological results.

PMID- 16290275
TI  - Tracing the history of Galalpha1-4Gal on glycoproteins in modern birds.
AB  - Galalpha1-4Gal is typically found in mammalian glycolipids in small quantities,
      and recognized by some pathogens, such as uropathogenic Escherichia coli. In
      contrast, glycoproteins containing Galalpha1-4Gal were rarely found in
      vertebrates except in a few species of birds and amphibians until recently.
      However, we had previously reported that pigeon (Columba livia) egg white and
      serum glycoproteins are rich in N-glycans with Galalpha1-4Gal at non-reducing
      termini. Our investigation with egg white glycoproteins from 181 avian species
      also revealed that the distribution of (Galalpha1-4Gal)-containing glycoproteins
      was not rare among avians, and is correlated with the phylogeny of birds. The
      differentiated expression was most likely emerged at earlier stage of
      diversification of modern birds, but some birds might have lost the facility for
      the expression relatively recently.

PMID- 16290273
TI  - Consolidation of motor memory.
AB  - An issue of great recent interest is whether motor memory consolidates in a
      manner analogous to declarative memory--that is, with the formation of a memory
      that progresses over time from a fragile state, which is susceptible to
      interference by a lesion or a conflicting motor task, to a stabilized state,
      which is resistant to such interference. Here, we first review studies that
      examine the anatomical basis for motor consolidation. Evidence implicates
      cerebellar circuitry in two types of associative motor learning--eyelid
      conditioning and vestibulo-ocular reflex adaptation--and implicates primary motor
      cortex in skilled finger movements. We also review evidence for and against a
      consolidation process for adaptation of arm movements. We propose that
      contradictions have arisen because consolidation can be masked by inhibition of
      memory retrieval.

PMID- 16290276
TI  - Why are HIV-1 fusion inhibitors not effective against SARS-CoV? Biophysical
      evaluation of molecular interactions.
AB  - The envelope spike (S) glycoprotein of the severe acute respiratory syndrome
      associated coronavirus (SARS-CoV) mediates the entry of the virus into target
      cells. Recent studies point out to a cell entry mechanism of this virus similar
      to other enveloped viruses, such as HIV-1. As it happens with other viruses
      peptidic fusion inhibitors, SARS-CoV S protein HR2-derived peptides are potential
      therapeutic drugs against the virus. It is believed that HR2 peptides block the
      six-helix bundle formation, a key structure in the viral fusion, by interacting
      with the HR1 region. It is a matter of discussion if the HIV-1 gp41 HR2-derived
      peptide T20 (enfuvirtide) could be a possible SARS-CoV inhibitor given the
      similarities between the two viruses. We tested the possibility of interaction
      between both T20 (HIV-1 gp41 HR2-derived peptide) and T-1249 with S protein HR1-
      and HR2-derived peptides. Our biophysical data show a significant interaction
      between a SARS-CoV HR1-derived peptide and T20. However, the interaction is only
      moderate (K(B)=(1.1+/-0.3)x10(5) M(-1)). This finding shows that the reasoning
      behind the hypothesis that T20, already approved for clinical application in AIDS
      treatment, could inhibit the fusion of SARS-CoV with target cells is correct but
      the effect may not be strong enough for application.

PMID- 16290277
TI  - Inhibition of drug-resistant HIV-1 by RNA interference.
AB  - RNA interference is a powerful tool used to inhibit human immunodeficiency virus
      type 1 (HIV-1) replication in vitro. Almost all HIV-1 genes have been targets for
      small interfering RNA (siRNA) molecules, and HIV-1 replication can be
      specifically and successfully inhibited by this technique. RNA interference has
      been proposed as an alternative strategy to inhibit replication of drug-resistant
      viruses that emerge during suboptimal antiretroviral therapy for HIV-1. To
      investigate specific inhibition of drug-resistant HIV-1 by RNA interference, we
      designed siRNA molecules that recognize codons 181-188 of the reverse
      transcriptase (RT) gene of wild-type HIV-1 and HIV-1 carrying the M184V mutation,
      which confers high-level resistance to the RT inhibitor lamivudine. Using viral
      variants with single point mutations at codon 184, we measured the impact of
      these mutations on virus replication. We have demonstrated that siRNA targeting
      either wild-type HIV-1 or M184V variants inhibits replication of the
      corresponding virus, but does not influence replication of virus with a mismatch
      in the targeted region. Combining two effective siRNAs did not show synergistic
      inhibitory effect on HIV-1 replication. However, a combination of lamivudine and
      siRNA-M184V was very effective in inhibiting replication of both wild-type and
      variant M184V viruses in mixed infection experiments. Taken together, these
      results demonstrate that RNA interference might be useful in the treatment of
      drug-resistant HIV-1 infection.

PMID- 16290279
TI  - Risks and benefits of immunizing pregnant women: the risk of doing nothing.
AB  - The medical, social and legal risks of immunizing pregnant women are obstacles
      preventing the initiation of programs to immunize women for their protection and
      for their infant's protection. Recent projects devoted to vaccine development
      have focused on protecting newborns and infants. But there are many other reasons
      for developing or utilizing vaccines before or during pregnancy, beyond the
      protection of the newborn. Besides the usual reasons for utilizing immunizations
      to protect the mother and the neonate, the threat of bio-terrorism adds a new
      dimension to the necessity for addressing this issue. The potential advantages
      for thinking about vaccinating pregnant women include an array of possible
      programs associated with risks and benefits. The immunization of pregnant women
      or women of reproductive age has multiple purposes: to protect the mother, to
      protect the newborn and infant and to prevent diseases and complications of
      pregnancy. (1) Preparation of vaccines against infectious agents that are known
      to result in reproductive pathology and congenital malformation if the infection
      of the mother occurs during pregnancy. (2) To utilize vaccines used routinely to
      protect the non-pregnant population, for administration during pregnancy, i.e.,
      influenza, tetanus and other vaccines. Should these vaccines and other routinely
      used vaccines for children and non-pregnant adults be administered to women
      during pregnancy if they are medically indicated? (3) Utilization of vaccines to
      protect women from diseases to which they are susceptible because of pregnancy
      (poliomyelitis, hepatitis). (4) Utilization of vaccines for use before or during
      pregnancy, primarily to protect the newborn and infant via maternal
      transplacental antibodies, i.e., GBD (group B streptococcus). (5) The prevention
      of intrauterine infection that has been alleged to initiate premature labor. (6)
      The preparation of a vaccine for use before or during pregnancy to protect both
      the mother and the neonate, i.e., botulism toxin vaccine. The regulatory agencies
      and the vaccine producers will need a great deal of objective scientific advice
      and support and it is the scientific community's responsibility to provide that
      support. If the scientific and medical community ignores the opportunity to
      develop vaccines that could reduce the occurrence of reproductive and
      developmental problems, then we can be accused of acquiescing to the "risk of
      doing nothing."

PMID- 16290278
TI  - Hepatitis B virus-neutralizing anti-pre-S1 human antibody fragments from large
      naive antibody phage library.
AB  - We report the construction of a large nonimmunized human phage antibody library
      in single-chain variable region fragment (scFv) format, which allowed the
      selection of antibodies that neutralize hepatitis B virus (HBV) in vitro. We
      generated 1.1 x 10(10) independent scFv clones using the cDNA of functional
      variable (V) gene segments of heavy and light chains purified from the peripheral
      blood mononuclear cells of 50 nonimmunized human donors. Using BIAcore, we
      selected two clones that recognized pre-S1 and neutralized pre-S1 and HBV binding
      to Chang liver cells. Clone G10 had the highest affinity (K(D)=1.69 x 10(-7)M),
      which was higher than that of clone 1E4 that was generated previously from a
      heavy chain-shuffled immune library. The off-rates of clones were within 10(-3)s(
      1) as determined by BIAcore and were comparable to those of antibodies derived
      from a normal secondary immune response. In the inhibition assays of pre-S1 and
      virus binding to Chang liver cells using flow cytometry and the polymerase chain
      reaction, G10 had better neutralizing activity than 1E4. The new phage library
      may be a valuable source of antibodies with reasonable affinities to different
      targets, and the anti-pre-S1 G10 may be a good candidate for immunoprophylaxis
      against HBV infection.

PMID- 16290280
TI  - Spatio-temporal analysis of locomotion in BALB/cByJ and C57BL/6J mice in
      different environmental conditions.
AB  - We analysed spatial and temporal characteristics of mouse locomotion and
      investigated whether mouse gait differed between strains and environments. To
      this end, we used two inbred strains of mice (BALB/cByJ and C57BL/6J) known for
      their contrasting inherent level of anxiety, in three different visual
      surroundings. The animal position was determined relative to each environment.
      Gait cycle, defined as the sequence of limb movements, was analysed relative to
      time. We also recorded spatial parameters of gait such as stride length, track
      width and footfall characteristics. These measures allowed us to obtain an
      accurate description of locomotion and to assess subtle modifications of the
      gait. We found that mice adjusted their position in space, posture and gait in
      order to either stabilize their body on the ground in a potentially unsafe
      environment, or to optimize propulsion and maneuverability in a safer location.
      In addition, the two strains of mice used different strategies, suggesting that
      the inherent level of emotionality may affect the organization of locomotion in
      mice. We further concluded that higher structures of the central nervous system
      are involved in the online control of locomotion.

PMID- 16290281
TI  - Effects of the 5-HT(7) receptor antagonist SB-269970 microinjected into the
      dorsal raphe nucleus on REM sleep in the rat.
AB  - The effects of SB-269970, a selective 5-HT(7) receptor antagonist, on spontaneous
      sleep were studied in adult rats implanted for chronic sleep recordings. SB
      269970 was infused directly into the dorsal raphe nucleus (DRN) during the light
      phase. The 5-HT(7) receptor antagonist (0.25-1.0 mM) induced a significant
      reduction of REM sleep and of the number of REM periods whereas REM sleep latency
      was augmented. Pretreatment with the GABA(A) receptor agonist muscimol (1.0-2.0
      mM), which by itself did not affect sleep variables, prevented the decrease of
      REM sleep induced by SB-269970 (1.0 mM). Our results indicate that the 5-HT(7)
      receptor is involved in the effect of DRN serotonergic (5-HT) neurons on
      brainstem structures that act to promote and induce REM sleep. We propose that
      the SB-269970-induced suppression of REM sleep is dependent upon the inhibition
      of GABA release in the DRN.

PMID- 16290282
TI  - Effects of injections of glucose into the dorsal striatum on learning of place
      and response mazes.
AB  - The present experiment tested the hypothesis that facilitation of striatal
      function with intra-striatal glucose injections would facilitate learning a
      striatum-dependent response maze and impair learning a hippocampus-dependent
      place maze. Food-deprived Sprague-Dawley male rats were trained to find food in a
      Y-maze. In the place version of the maze, rats were rewarded for learning to go
      to an arm located in a fixed location while in the response task rats were
      rewarded for consistently turning in the same direction at the choice point.
      Artificial cerebrospinal fluid (1 microL) containing either 0.7 nmol of glucose
      (control) or 20 nmol of glucose was injected bilaterally into the dorsal striatum
      immediately before training. The animals were trained to a criterion of 9/10
      correct choices. In the place maze, glucose injections impaired learning, as
      measured by number of trials required to reach 9/10 correct. However, in the
      response task, glucose injections did not enhance learning. A subsequent
      experiment examined the effects of intra-striatal glucose injections on
      acquisition of the response task under two different visual cue conditions,
      addition of an intra-maze light cue that predicted the correct arm or with
      removal of most visual extramaze cues. Glucose again failed to facilitate
      acquisition of the response task under these conditions. These findings suggest
      that facilitation of striatal function via intra-striatal glucose injections is
      sufficient to impair place learning but not to enhance response learning, perhaps
      separating the neurochemical mechanisms for striatal involvement in impairment of
      place and enhancement of response learning.

PMID- 16290284
TI  - Fast 3D-EM reconstruction using Planograms for stationary planar positron
      emission mammography camera.
AB  - At the University of Pisa we are building a PEM prototype, the YAP-PEM camera,
      consisting of two opposite 6 x 6 x 3 cm3 detector heads of 30 x 30 YAP:Ce finger
      crystals, 2 x 2 x 30 mm3 each. The camera will be equipped with breast
      compressors. The acquisition will be stationary. Compared with a whole body PET
      scanner, a planar Positron Emission Mammography (PEM) camera allows a better,
      easier and more flexible positioning around the breast in the vicinity of the
      tumor: this increases the sensitivity and solid angle coverage, and reduces cost.
      To avoid software rejection of data during the reconstruction, resulting in a
      reduced sensitivity, we adopted a 3D-EM reconstruction which uses all of the
      collected Lines Of Response (LORs). This skips the PSF distortion given by data
      rebinning procedures and/or Fourier methods. The traditional 3D-EM reconstruction
      requires several times the computation of the LOR-voxel correlation matrix, or
      probability matrix {p(ij)}; therefore is highly time-consuming. We use the sparse
      and symmetry properties of the matrix {p(ij)} to perform fast 3D-EM
      reconstruction. Geometrically, a 3D grid of cubic voxels (FOV) is crossed by
      several divergent 3D line sets (LORs). The symmetries occur when tracing
      different LORs produces the same p(ij) value. Parallel LORs of different sets
      cross the FOV in the same way, and the repetition of p(ij) values depends on the
      ratio between the tube and voxel sizes. By optimizing this ratio, the occurrence
      of symmetries is increased. We identify a nucleus of symmetry of LORs: for each
      set of symmetrical LORs we choose just one LOR to be put in the nucleus, while
      the others lie outside. All of the possible p(ij) values are obtainable by
      tracking only the LORs of this nucleus. The coordinates of the voxels of all of
      the other LORs are given by means of simple translation rules. Before making the
      reconstruction, we trace the LORs of the nucleus to find the intersecting voxels,
      whose p(ij) values are computed and stored with their voxel coordinates on a hard
      disk. Only the non-zero p(ij) are considered and their computation is performed
      just once. During the reconstruction, the stored values are loaded and are
      available in the random access memory for all of the operations of normalization,
      backprojection and projection: these are now performed rapidly, because the
      application of the translation rules is much faster than the probability
      computations. We tested the algorithm on Monte Carlo data fully simulating the
      typical YAP-PEM clinical condition. The adopted algorithm gives an excellent
      positioning capability for hot spots in the camera FOV. To use all of the
      possible skew LORs in the FOV avoids the software rejection of collected data.
      Reconstructed images indicate that a 5mm diameter tumor of 37 kBq/cm3, in an
      active breast with a 10:1 Tissue to Background ratio (T/B), with a 10 min
      acquisition, for a head distance of 5 cm, can be detected by the YAP-PEM with a
      SNR of 8.7+/-1.0. The obtained SNR values depend linearly on the tumor volume.
      The algorithm allows one to discriminate between two hot sources of 5.0 mm
      diameter if they do not lie on the same axis. The YAP-PEM is now in the assembly
      stage.

PMID- 16290283
TI  - Beneficial effects of exercise and its molecular mechanisms on depression in
      rats.
AB  - Exercise showed the beneficial effects on mental health in depressed sufferers,
      whereas, its underlying mechanisms remained unresolved. This study utilized the
      chronic unpredictable stress (CNS) animal model of depression to evaluate the
      effects of exercise on depressive behaviors and spatial performance in rats.
      Furthermore, we tested the hypothesis that the capacity of exercise to reverse
      the harmful effects of CNS was relative to the hypothalamo-pituitary-adrenal
      (HPA) system and brain-derived neurotrophic factor (BDNF) in the hippocampus.
      Animal groups were exposed to CNS for 4 weeks with and without access to
      voluntary wheel running. Stressed rats consumed significantly less of a 1%
      sucrose solution during CNS and exhibited a significant decrease in open field
      behavior. On the other hand, they showed impaired spatial performance in Morris
      water maze test 2 weeks after the end of CNS. Further, CNS significantly
      decreased hippocampal BDNF mRNA levels. However, voluntary exercise improved or
      even reversed these harmful behavioral effects in stressed rats. Furthermore,
      exercise counteracted a decrease in hippocampal BDNF mRNA caused by CNS. In
      addition, we also found that CMS alone increased circulating corticosterone
      (CORT) significantly and decreased hippocampal glucocorticoid receptor (GR) mRNA.
      At the same time, exercise alone increased CORT moderately and did not affect
      hippocampal GR mRNA levels. While, when both CNS and exercise were combined,
      exercise reduced the increase of CORT and the decrease of GR caused by CMS. The
      results demonstrated that: (1) exercise reversed the harmful effects of CNS on
      mood and spatial performance in rats and (2) the behavioral changes induced by
      exercise and/or CNS might be associated with hippocampal BDNF levels, and in
      addition, the HPA system might play different roles in the two different
      processes.

PMID- 16290286
TI  - Cytochrome P4501A is induced in endothelial cell lines from the kidney and lung
      of the bottlenose dolphin, Tursiops truncatus.
AB  - Marine mammals respond to the presence of polycyclic and planar halogenated
      aromatic hydrocarbons (PAH or PHAH) with the induced expression in endothelium of
      cytochrome P4501A1, regulated through the aryl hydrocarbon receptor (AHR)
      transcription factor. Physiological responses in other animals, such as edema and
      inflammation indicate that the endothelium may be compromised by exposure to AHR
      agonists, which are ubiquitous in the marine environment. In other mammals and
      fish the cellular and molecular consequences of exposure to AHR agonists have
      been elucidated in cultured endothelial cells. We have cultured and characterized
      cetacean endothelial cells (EC) and used them in induction studies. Endothelial
      cells were cultured from the lung and kidney of the bottlenose dolphin, Tursiops
      truncates, and exposed to the AHR agonists beta-naphthoflavone (betaNF) and
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). betaNF (1-3 microM) induced
      significant increases in CYP1A1 (O-deethylation of 7-ethoxyresorufin to
      resorufin; EROD) activity to 3.6 and 0.92 pmol/mg/min in lung and kidney EC,
      respectively. TCDD was more potent than betaNF, and more efficacious, with
      maximum induction of CYP1A1 activity of 10.1 and 15.2 pmol/mg/min in lung and
      kidney EC at 3-10 nM TCDD. The differential response indicates that the lung and
      kidney endothelial cells in culture retain the ability to respond in a selective
      manner to specific stimuli. Both the molecular mechanisms of induction and the
      physiological consequences, especially in the vasculature, of toxicant exposure
      can be studied in this system.

PMID- 16290285
TI  - Dry coating in a rotary fluid bed.
AB  - A highly efficient dry coating process was developed to obtain an enteric film
      avoiding completely the use of organic solvents and water. Using hydroxypropyl
      methylcellulose acetate succinate (HPMCAS) an enteric coat should be obtained
      without adding talc as anti-tacking agent because of problems arising from
      microbiological contamination. Further on, a method was developed preparing
      isolated films in order to determine the glass transition temperature (T(g)) and
      the required process temperature. The process was conducted in the rotary fluid
      bed with a gravimetric powder feeder achieving an exact dosage in contrast to
      volumetric powder feeder. A three way nozzle was aligned tangential to the pellet
      bed movement feeding simultaneously powder and plasticizer into the rotary fluid
      bed. The determined coating efficiency of the talc-free formulation was high with
      94% and storage stability regarding tacking could be achieved using colloidal
      silicium dioxide as top powder. The T(g) of the enteric coat could be determined
      analyzing the T(g) of isolated films obtained by coating celluloid spheres
      instead of pellets using the dry coating process in rotary fluid bed. The dry
      coating process has been demonstrated to be a serious alternative to conventional
      solvent or water based coating processes.

PMID- 16290287
TI  - Progesterone and Progestins in Human Pregnancy and Breast Cancer. Proceedings of
      the European Progestin Club Scientific Meeting, Amsterdam, the Netherlands, 5
      October 2004.

PMID- 16290289
TI  - Anticoagulation after cardioversion in atrial fibrillation: how long should we
      warfarinise for?

PMID- 16290288
TI  - A proposal for an appropriate central obesity diagnosis in Latin American
      population.

PMID- 16290290
TI  - The effect of atorvastatin on heart rate variability and lipoproteins in patients
      treated with coronary bypass surgery.
AB  - Statins reduce mortality in patients with coronary heart disease (CHD). An
      antiarrhythmic effect of statins has been suggested and reported as a possible
      contributing mechanism. The aim of this study was to examine whether atorvastatin
      had any effect on heart rate variability (HRV), an important predictor of sudden
      cardiac death. Eighty patients previously treated with coronary artery bypass
      grafting (CABG) were studied. The study was designed as a randomized, placebo
      controlled, double blinded crossover study. The patients were randomized in two
      groups, and were treated with 80 mg atorvastatin or placebo for 6 weeks before
      crossing over to the opposite treatment for another 6 weeks. There was no washout
      between treatments. Twenty-four-hour Holter recording and plasma lipids and
      lipoprotein measurements were performed at baseline and after each 6-week period.
      There was no change in HRV indices after treatment with 80 mg atorvastatin for 6
      weeks. A significant reduction in total cholesterol (46%, p</=0.001), LDL
      cholesterol (61%, p</=0.001) and triglycerides (35%, p</=0.001) were observed
      during treatment with atorvastatin. Therapy with 80 mg atorvastatin daily for 6
      weeks reduced total cholesterol, LDL cholesterol and triglycerides significantly,
      while there was no effect on 24-h HRV indices. The study therefore does not lend
      support for any effect of atorvastatin on HRV after 6 weeks of treatment in
      patients treated with CABG.

PMID- 16290291
TI  - Cardiomyocyte apoptosis in cocaine-induced myocarditis with involvement of bundle
      of His and left bundle branch.
AB  - Cocaine abuse can cause degenerative and inflammatory alterations of the
      myocardium. Cocaine-induced myocarditis has been previously described, but mostly
      in chronic cocaine addicts. Among several pathogenetic mechanisms of cocaine
      related myocardial damage, the myocardial adrenergic stress and cardiomyocytes
      apoptosis have been recently proposed. We report an unusual case of myocarditis
      involving the bundle of His and left bundle branch and cardiac myocytes apoptosis
      in otherwise healthy occasional cocaine abuser.

PMID- 16290293
TI  - Behavior of 210Po and 210Pb in high background areas of coastal Kerala on the
      south west coast of India.
AB  - This paper deals with the distribution and behavior of (210)Po and (210)Pb in
      beach sand and surface soil samples from the Quilon district of Kerala. Beach
      sand and soil samples were collected and analyzed for (210)Po and (210)Pb
      radionuclides using standard radiochemical analytical techniques. Mean activities
      of (210)Po and (210)Pb were found to be maximum in the samples collected at 20 m
      away from waterline. Among the beach sand samples, the activities of radionuclide
      were found to be maximum for samples from most of the regions of Chavara and few
      regions of Neendakara. The activity of (210)Po was found to vary from 2.4 to 20.5
      Bq kg(-1) with a mean value of 8.3 Bq kg(-1) at the water line, 2.5-19.9 Bq kg(
      1) with a mean value of 10.2 Bq kg(-1) at 20 m away from the waterline, and 2.1
      6.7 Bq kg(-1) with a mean value of 3.5 Bq kg(-1) at 40 m away from waterline. The
      respective values found for (210)Pb were from 1.2 to 48.2 Bq kg(-1) with a mean
      value of 14.9, 11.3-34.2 Bq kg(-1) with a mean value of 19.8 Bq kg(-1) and 2.3 to
      18.3 Bq kg(-1) with a mean value of 8.7 Bq kg(-1). The depth profile study
      indicated the mean activity of (210)Po to decrease with depth for samples
      collected 20 m away from waterline whereas the activity slightly increases with
      depth 40 m away from sea. The activity concentration of (210)Po and (210)Pb in
      surface beach sand shows good correlation, with a correlation coefficient 0.81.

PMID- 16290294
TI  - Effect of pH, ionic strength and fulvic acid on the sorption and desorption of
      cobalt to bentonite.
AB  - Humic substances and bentonite have attracted great interest in radioactive waste
      management. Here the sorption of cobalt on bentonite in the presence and absence
      of fulvic acid (FA) under ambient conditions was studied. The effects of pH,
      ionic strength, FA and solution concentrations on cobalt sorption to bentonite
      were also investigated using batch techniques. The results indicate that the
      sorption of cobalt is strongly dependent on pH and is independent of ionic
      strength under our experimental conditions. Surface complexation is considered
      the main mechanism of cobalt sorption to bentonite. In the presence of FA, little
      effect of FA on cobalt sorption was found at pH<6; a positive effect of FA on
      cobalt sorption was found for pH 6-8; and a negative effect of FA on cobalt
      sorption was found at pH>8. The addition sequences of FA/Co(2+) to the bentonite
      suspension on the sorption of cobalt to FA-coated bentonite were also studied.
      The results indicated that the sorption is not influenced by the addition
      sequences. Some possible mechanisms are discussed.

PMID- 16290292
TI  - QSAR analysis of meclofenamic acid analogues as selective COX-2 inhibitors.
AB  - The use of quantitative structure-activity relationships, since its advent, has
      become increasingly helpful in understanding many aspects of biochemical
      interactions in drug research. This approach was utilized to explain the
      relationship of structure with biological activity of selective COX-2 inhibitors.
      The enormity of the COX-2 discovery is reflected in the unprecedented speed at
      which research laboratories have sought to validate its clinical implications.
      Presented herein is a series of 21 derivatives of meclofenamic acid with
      selective COX-2 inhibitory activity. Several statistically significant regression
      expressions were obtained for both COX-1 and COX-2 inhibition using sequential
      multiple linear regression analysis method. Two of these models were selected and
      validated further, which revealed the importance of Kier molecular flexibility
      index for COX-2 inhibitory activity and the number of hydrogen bond donor atoms
      for COX-1 inhibitory activity. Additionally, linear correlation of molecular
      flexibility with COX-1 and COX-2 inhibitory activities revealed that flexibility
      of molecules at COX-2 active site can improve the selectivity of COX-2
      inhibitors.

PMID- 16290296
TI  - Using rare earth element tracers and neutron activation analysis to study rill
      erosion process.
AB  - Spatially averaged soil erosion data provide little information on the process of
      rill erosion. The dynamically varied data on the temporal and spatial
      distributions in the rill erosion process are needed to better understand the
      erosion process and reveal its innate characteristics. The objectives of this
      study were to examine the feasibility and effectiveness of rare earth element
      (REE) tracers and the neutron activation analysis (NAA) method on the study of
      the rill erosion process and to reveal quantitatively the relationships and
      characteristics of temporal and spatial distributions of sediment yield in rill
      erosion. Four REEs were used to study the changeable process of rill erosion at 4
      slope positions. Four water inflow rates were applied to a 0.3 x 5 m soil bed at
      3 slopes of 10.5%, 15.8% and 21.2% in scouring experiments. All of the runoff was
      collected in the experiment. Each sample was air-dried and well mixed. Then 20 g
      of each sample was sieved through 100-mesh and about a 50 mg sample was weighed
      for analysis of the four elemental compositions by NAA. Results indicate that the
      REE tracers and NAA method can be used to not only quantitatively determine soil
      erosion amounts on different slope segments, but also to reveal the changeable
      process of rill erosion amount. All of the relative errors of the experimental
      results were less than 25%, which is considered satisfactory on the study of rill
      erosion process.

PMID- 16290295
TI  - A simple model for quantification of the radiobiological effectiveness of the
      10B(n,alpha)7Li capture reaction in BNCT.
AB  - A simple model has been developed for predicting radiobiological effectiveness of
      the neutron capture reaction in boron neutron capture therapy. This model was
      derived from the relationship between the cell survival from the boron capture
      reaction, the intracellular boron concentration, and the thermal neutron fluence.
      We found that the cell-killing effect of the boron capture reaction was well
      described using a power function of the intracellular boron concentration. Hence
      the relationship between cell survival from the boron capture reaction,
      intracellular boron concentration, and the thermal neutron fluence could be
      determined using a simple mathematical equation. We consider that our current
      approach is more appropriate and realistic than the conventional theoretical
      mathematical model used to estimate the radiobiological effectiveness of the
      neutron capture reaction in boron neutron capture therapy.

PMID- 16290297
TI  - (3)He-particle-induced reactions on (nat)Sb for production of (124)I.
AB  - Excitation functions of the reactions (nat)Sb((3)He,xn)(124,123,121)I were
      measured from their respective thresholds up to 35 MeV, with particular emphasis
      on data for the production of the medically important radionuclide (124)I. The
      conventional stacked-foil technique was used. From the experimental data the
      theoretical yields of the three investigated radionuclides were calculated. The
      yield of (124)I over the energy range E9(30He) = 35 --> 13 MeV amounts to 0.95
      MBq/microA h. The radionuclidic impurities are discussed. A comparison of (3)He-
      and alpha-particle-induced reactions on antimony for production of (124)I is
      given. The alpha-particle-induced reaction on enriched (121)Sb and the (3)He
      particle-induced reaction on enriched (123)Sb would lead to comparable (124)I
      yields, but the level of impurities in the latter case would be somewhat higher.

PMID- 16290298
TI  - The role of spatial mixing in the spread of foot-and-mouth disease.
AB  - A model of epidemic dispersal (based on the assumption that susceptible cattle
      were homogeneously mixed over space, or non-spatial model) was compared to a
      partially spatially explicit and discrete model (the spatial model), which was
      composed of differential equations and used geo-coded data (Euclidean distances
      between county centroids). While the spatial model accounted for intra- and inter
      county epidemic spread, the non-spatial model did not assess regional
      differences. A geo-coded dataset that resembled conditions favouring homogeneous
      mixing assumptions (based on the 2001 Uruguayan foot-and-mouth disease epidemic),
      was used for testing. Significant differences between models were observed in the
      average transmission rate between farms, both before and after a control policy
      (animal movement ban) was imposed. They also differed in terms of daily number of
      infected farms: the non-spatial model revealed a single epidemic peak (at,
      approximately, 25 epidemic days); while the spatial model revealed two epidemic
      peaks (at, approximately, 12 and 28 days, respectively). While the spatial model
      fitted well with the observed cumulative number of infected farms, the non
      spatial model did not (P<0.01). In addition, the spatial model: (a) indicated an
      early intra-county reproductive number R of approximately 87 (falling to <1
      within 25 days), and an inter-county R<1; (b) predicted that, if animal movement
      restrictions had begun 3 days before/after the estimated initiation of such
      policy, cases would have decreased/increased by 23 or 26%, respectively. Spatial
      factors (such as inter-farm distance and coverage of vaccination campaigns,
      absent in non-spatial models) may explain why partially explicit spatial models
      describe epidemic spread more accurately than non-spatial models even at early
      epidemic phases. Integration of geo-coded data into mathematical models is
      recommended.

PMID- 16290299
TI  - Testing of primers for the study of cyanobacterial molecular diversity by DGGE.
AB  - Denaturing Gradient Gel electrophoresis (DGGE) is a PCR-based technique which is
      widely used in the study of microbial communities. Here, the use of the three
      specific 16S rRNA cyanobacterial specific primers CYA359F, CYA781R(a) and
      CYA781R(b) on the assessment of the molecular diversity of cyanobacterial
      communities is examined. Assignments of the reverse primers CYA781R(a) and
      CYA781R(b) with cyanobacterial strain sequences showed that the former
      preferentially targets filamentous cyanobacteria whereas the latter targets
      unicellular cyanobacteria. The influence of the GC clamp position on the forward
      or on reverse primer and the use of the two reverse primers separately or in
      equimolar mixture were investigated. Three environmental samples were subjected
      to amplification with 6 combinations of primers. The 6 banding patterns as well
      as the sequences of the bands extracted were analysed and compared. In addition,
      to assess the effect of the position of the GC clamp, the melting profiles of the
      sequences of Aphanizomenon flos-aquae PMC9707 and Synechococcus sp. MH305 were
      determined, with the GC clamp in the 3' or 5' position. Results showed that the
      use of two separate amplifications allowed a more complete study of the molecular
      diversity of the cyanobacterial community investigated. Furthermore, similar
      richness and identical phylogenetic assignments of extracted bands were obtained
      irrespective of the positioning of the GC clamp.

PMID- 16290300
TI  - Assessment of drug-induced QT interval prolongation in conscious rabbits.
AB  - INTRODUCTION: Most preclinical trials are designed to identify potential
      torsadogenicity test only for surrogates of torsade de pointes, most commonly
      prolongation of the heart rate corrected QT interval (QTc). This study was
      conducted to determine which correction method best accounts for the effects of
      changes in the RR interval on the QT interval of conscious rabbits. This study
      was also conducted to validate the use of conscious, sling-trained rabbits to
      assess the QTc interval, and to evaluate the reliability and accuracy of this
      preparation in predicting drug-induced QTc prolongation in humans. METHODS: ECGs
      were recorded via bipolar transthoracic ECG leads in 7 conscious rabbits
      previously trained to rest quietly in slings. The heart rate was slowed with 2.0
      mg/kg zatebradine to assess the effects of heart rate on the QT interval. The
      same ECG and sling preparation was used to evaluate the effects in of three drugs
      known to be torsadogenic in humans (cisapride, dofetilide and haloperidol), two
      drugs known to be non-torsadogenic in humans (propranolol and enalaprilat) and a
      control article (vehicle). All of the test articles were administered
      intravenously to 4 rabbits, and both RR and QT intervals were measured and the
      corrected QT values were calculated by an investigator blinded to the test
      article, utilizing our own algorithm (QTc=QT/(RR)(0.72)) which permitted the
      least dependency of QTc on RR interval. RESULTS: The following regression
      equations were obtained relating QT to RR: QT=2.4RR(0.72), r(2)=0.79, with RR
      intervals varying between 210 and 350 ms. QTc lengthened significantly in all
      conscious rabbits given intravenous cisapride, dofetilide and haloperidol
      (p<0.05), and QTc did not change with DMSO (vehicle control), propranolol or
      enalaprilat. DISCUSSION: Results indicate that a bipolar transthoracic ECG
      recorded in conscious, sling-trained rabbits may provide an easy and economical
      methodology useful in predicting QTc lengthening of novel pharmacological
      entities.

PMID- 16290301
TI  - Force overestimation during tourniquet-induced transient occlusion of the
      brachial artery and possible underlying neural mechanisms.
AB  - A vascular occlusion by a tourniquet inflated at the proximal end of the upper
      arm is suggested to affect the estimation of exertion force level. In the first
      part of this study, subjects were asked to estimate the isometric force exerted
      by the occluded hand with that of the other hand (matching experiment). We found
      that the perceived force with arterial occlusion was always overestimated. To
      examine the underlying neural mechanism for this phenomenon, in the second part,
      the somatosensory evoked potentials (SEPs) and nerve action potential (NAP) were
      recorded following electrical median nerve stimulation with or without arterial
      occlusion. Moreover, the maximum motor response (M response) to median nerve
      stimuli at the axilla was recorded from the skin surface of the thenar eminence
      muscle of the hand during with arterial occlusion. The N20 of SEP and NAP at
      Erb's point were unaffected by the arterial occlusion, and the M response was
      also unchanged. These results suggest that the tourniquet-induced transient
      occlusion of the brachial artery does not seriously affect median nerve function.
      Thus, it is likely that the primary responsible factor for the overestimation of
      perceived force exertion during arterial occlusion is the centrally generated
      motor command as previously hypothesized by McCloskey [McCloskey, D.I., Ebeling,
      P., Goodwin, G.M., 1974. Estimation of weights and tensions and apparent
      involvement of a "sense of effort". Exp Neurol. 42, 220-232; McCloskey, D.I.,
      1978. Kinesthetic sensibility. Physiol. Rev. 58, 763-820; McCloskey, D.I., 1981.
      Corollary discharge and motor commands and perception. In: Brookhart, J.M.,
      Mountcastle, V.B. (Eds.), Handbook of Physiology. American Physiological Society,
      Bethesda, pp. 1415-1447].

PMID- 16290302
TI  - Beta-site APP cleaving enzyme 1 (BACE1) is increased in remaining neurons in
      Alzheimer's disease brains.
AB  - Alzheimer's disease (AD) is characterized by the extensive deposition of amyloid
      beta protein (Abeta) in the brain cortex. Abeta is produced from beta-amyloid
      precursor protein (APP) by beta-secretase and gamma-secretase. beta-Secretase has
      been identified as beta-site APP cleaving enzyme1 (BACE1). We produced rabbit
      polyclonal antibodies against the amino and the carboxyl terminals of BACE1.
      Using these antibodies, BACE1 was characterized in temporal lobe cortices by
      Western blotting and immunohistochemistry. Immunohistochemical studies employing
      anti-GFAP and anti-MAP2 antibodies as well as anti-BACE1 antibodies showed that
      BACE1 was expressed exclusively in neurons but not in glial cells. Brain samples
      were directly extracted by 0.5% SDS and analyzed by Western blotting and
      densitometer. Although the mean level of BACE1/mg protein in AD brains was not
      increased, the ratio of BACE1 to MAP2 or to NSE was significantly increased
      compared with that in control brains. Taken together, these findings suggest that
      those neurons that survive in AD brains might generate more BACE1 than normal
      neurons in control brains, indicating that increased BACE1 activity could be one
      of the causes of AD. This could justify the development of anti-BACE1 drugs for
      AD treatment.

PMID- 16290303
TI  - Enterocin A production by Enterococcus faecium FAIR-E 406 is characterised by a
      temperature- and pH-dependent switch-off mechanism when growth is limited due to
      nutrient depletion.
AB  - The biokinetics of cell growth and bacteriocin production of Enterococcus faecium
      FAIR-E 406 was studied as a function of temperature (20-45 degrees C) and pH (5.5
      8.5) using de Man-Rogosa-Sharpe medium. Growth of E. faecium FAIR-E 406 was
      characterized by three successive growth phases and was modelled with the
      mechanistic nutrient depletion model. Bacteriocin production showed primary
      metabolite kinetics but was limited to the early growth phase. The critical
      biomass for switching off bacteriocin production was dependent on medium pH and
      incubation temperature, and was inversely correlated with the specific
      bacteriocin production. Doubling the concentration of the nitrogen source as well
      as a step-wise pH increase shifted the bacteriocin production towards a higher
      switch-off cell density.

PMID- 16290304
TI  - Campylobacter jejuni loss of culturability in aqueous microcosms and ability to
      resuscitate in a mouse model.
AB  - Water is known as one of the main transmission routes of Campylobacter and
      contributes to increase the number of sporadic infections and outbreaks.
      Campylobacter jejuni persists in the environment, especially in water, in a
      viable but non-culturable (VBNC) form that is thought to be a possible cause of
      water-borne outbreaks. In this study, we evaluated the loss of culturability and
      viability of 9 C. jejuni strains of clinical origin and one ATCC reference strain
      when kept at 4 degrees C in artificial sea water (ASW). Culturability was
      measured as colony-forming units while viability was evaluated by CTC-DAPI double
      staining and the combined CTC-specific fluorescent antibody technique (CTC-FA).
      When cultured on Columbia Agar plates, strains exhibited different growth
      profiles which allowed to classify them into three different groups. Both
      techniques used to monitor the viability of the bacterial cells showed that C.
      jejuni strains survived in the VBNC form in the microcosms through a period
      lasting from 138 to 152 days. The recovery of C. jejuni VBNC forms to
      culturability, as evidenced by cell division, was obtained by passage in the
      mouse intestine. Our results indicate that C. jejuni VBNC cells were able to
      remain in this state for a few months and regain their culturability after in
      vivo passage depending on their lasting in the VBNC state, which affects the
      number of respiring bacteria. In fact, the resuscitation was achieved when the
      number of respiring bacteria became higher than 10(4) cell/ml. Therefore, a
      relatively high microbial titer of respiring bacteria in the VBNC state seems to
      be important for the resuscitation and subsequent intestinal colonisation.

PMID- 16290305
TI  - Characterization of heterologous hemoglobin and flavohemoglobin promoter
      regulation in Escherichia coli.
AB  - Bacterial hemoglobins and flavohemoglobins have been used to improve cell growth
      and productivity in biotechnological applications. The expression of globin genes
      can be induced by reducing the oxygen supply or applying external stressors,
      which provide a simple and inexpensive mechanism for induction of heterologous
      protein production. It is in the interest of the biotechnological industry to
      seek new promoters, which are non-patented, cheap and simple to induce.
      Therefore, new globin gene promoters have been isolated from Campylobacter
      jejuni, Bacillus subtilis, Deinococcus radiodurans, Streptomyces coelicolor, and
      Salmonella typhi. The goal was to obtain insights about the regulation mechanisms
      of these promoters in Escherichia coli using in silico and experimental methods.
      The recognition of these promoters by the E. coli transcriptional machinery was
      first analyzed by computational methods. Computer analysis revealed that all the
      promoters, except the promoter of S. coelicolor, should be functional in E. coli
      and most of them also contain putative binding sites for ArcA, CRP, and FNR
      global regulators. Furthermore, the expression profiles of the promoters fused to
      the chloramphenicol acetyl transferase gene were analyzed under various
      conditions using E. coli mutants devoid of regulatory molecules. In vivo
      regulation studies of globin promoters mainly verified the in silico predictions.

PMID- 16290306
TI  - High level expression of monomeric and dimeric human alpha1,3-fucosyltransferase
      V.
AB  - alpha3/4-Fucosyltransferases play a crucial role in inflammatory processes and
      tumor metastasis. While several human fucosyltransferases (FucTs) with different
      acceptor substrate specificities have been identified, the design of specific
      inhibitors for therapeutic approaches is hampered by the lack of structural
      information. In this study, we evaluated the expression of different constructs
      of human fucosyltransferase V to generate the large amounts required for
      structural studies. The truncated constructs lacking the transmembrane region and
      the cytosolic N-terminus, were expressed in baculovirus-infected Trichoplusia ni
      (Tn) insect cells and in two non-lytic expression systems, stably transfected
      human HEK 293 and T. ni cells. Since secretion of some glycosyltransferases is
      controlled by formation of dimeric molecules via disulfide bonds, one of the
      fucosyltransferase V constructs contained the N-terminal cysteine residue 64 for
      dimerization, whereas this residue was replaced in the other construct by serine.
      In both human and insect cells dimerization did not prove to be essential for
      efficient expression and secretion. On the basis of enzymatic activity, the yield
      of secreted fucosyltransferase V was approximately 10-fold higher in stably
      transfected insect cells than in HEK 293 cells. In particular the monomeric form
      of the enzyme provides a valuable tool for structural analyses to elucidate the
      fine specifity of fucosyltransferase V-mediated fucosylation of Lewis type
      glycans.

PMID- 16290307
TI  - Intracellular distribution of rotavirus structural proteins and virus-like
      particles expressed in the insect cell-baculovirus system.
AB  - The production of virus-like particles (VLP) is of interest to several fields.
      However, little is known about their assembly when they are expressed in insect
      cells, as it occurs in conditions different to those of native virus. Knowledge
      of the localization of recombinant proteins and of the site of accumulation of
      VLP can increase the understanding of VLP assembly and be useful for proposing
      production strategies. In this work, the rotavirus proteins VP6 and the fusion
      protein GFPVP2 were expressed in High Five insect cells. Recombinant proteins and
      rotavirus-like particles (RLP) were located and visualized by confocal,
      epifluorescence and electron microscopy. Single-layered (sl) RLP (conformed by
      GFPVP2) accumulated in the cytoplasm as highly ordered aggregates. In contrast,
      VP6 formed fibrillar structures composed of various tubes of VP6 that were not
      associated to microtubules. Coexpression of GFPVP2 and VP6 altered the
      distribution of both proteins. VP6 formed aggregates, even when all other
      conditions of individual protein expression remained unchanged. Double-layered
      (dl) RLP were observed in dense zones of the cytoplasm, but were not in ordered
      aggregates. It was determined that the assembly of both slRLP and dlRLP occurs
      intracellularly. Accordingly, strategies for the optimum assembly of dlRLP should
      guarantee that each cell produces both recombinant proteins.

PMID- 16290308
TI  - Hydrolyses and transglycosylations performed by purified alpha-D-glucosidase of
      the marine mollusc Aplysia fasciata.
AB  - The purification and characterisation of the alpha-glucosidase from the marine
      mollusc Aplysia fasciata are reported. Overall substrate specificity of the pure
      enzyme for both hydrolytic and transglycosylation reactions was studied.
      Remarkable characteristics of this enzyme are indicated by the results of the
      interesting survey of transglycosylation reactions reported: pyridoxine
      glucosylation, synthesis of chromophoric (pNP) di- and trisaccharides,
      glucosylation of cellobiose and sucrose. For these last two acceptors both the
      yields of reactions and the concentrations of products are comparable to those
      obtained using glycosyl transferases; in addition, synthesis of pyridoxine and
      chromophoric glycosides were still possible using a 1:1 ratio maltose:acceptor
      which is a very interesting characteristic from a synthetic point of view
      (effortless purification, productivity of each reaction batch, etc.).

PMID- 16290309
TI  - Treatment and outcomes of treating of hepatocellular carcinoma among Medicare
      recipients in the United States: a population-based study.
AB  - BACKGROUND/AIMS: There are several treatment alternatives available for patients
      diagnosed with hepatocellular carcinoma (HCC). Yet, neither the extent to which
      potentially curative or palliative therapy is used to treat HCC, nor the
      determinants of using such therapies are known. Further, it is unclear how
      effective different modalities are for treating HCC. METHODS: We used the linked
      SEER-Medicare dataset to identify patients diagnosed with HCC between 1992 and
      1999. We identified 2963 patients with continuous Medicare enrollment who were
      not enrolled in a Medicare-HMO. HCC treatments were categorized as potentially
      curative therapy (resection, transplant, local ablation), or palliative (trans
      arterial chemoembolization (TACE), chemotherapy), and no therapy. Demographic
      (age, sex, race, geographic region), clinical (comorbidity, risk factors and
      severity of liver disease) and tumor factors (tumor size, extent of disease) were
      examined as potential determinants of therapy, as well as survival in univariate
      and multivariable analyses. Survival curves were also generated and compared
      among the different treatment modalities. RESULTS: The median age at diagnosis
      was 74 years (range: 32-105), and most patients (91%) were older than 65 years.
      Approximately 68% were White, 10% Black, 4% Hispanic, 8% Asian, and 9% were of
      other race. Thirteen percent of the patients received potentially curative
      therapy (transplant 0.9%, resection 8.2%, local ablation 4.1%), 4% received TACE,
      57% received other palliative therapy, and 26% received no specific therapy. Only
      34% of 513 patients with single lesions, and 34% of 143 patients with lesions
      <3.0 cm received potentially curative therapy. However, 19.2% of patients with
      unfavorable tumor features (lesion >10.0 cm) received such therapy. Among
      patients who received potentially curative therapy (n=392), resection was the
      most common procedure (n=243, 62%) followed by local ablation (n=122, 31%) and
      finally transplantation (n=27, 7%). In regression analyses, geographic variations
      in the extent and type of curative therapy persisted after adjusting for
      demographic, clinical, and tumor features. Median overall survival was 104 days
      following HCC diagnosis with the longest survival in the transplant group (852
      days) and the shortest survival in the group with no treatment (58 days). In the
      survival analysis, transplantation led to the longest survival, followed by
      resection. Neither ablation nor TACE yielded prolonged survival (3 year survival
      was less than 10%). CONCLUSIONS: In this predominantly 65 years and older
      Medicare population, there are marked geographic variations in the management of
      HCC that seem to be at least as important as clinical and tumor-related features
      in determining the extent and type of HCC therapy. There is underutilization of
      potentially curative therapy, even among those with favorable tumor features.

PMID- 16290310
TI  - A patient with novel ABCB11 gene mutations with phenotypic transition between
      BRIC2 and PFIC2.
AB  - We describe a PFIC2 patient with a good response to ursodeoxycholic acid for 9
      years. We found two novel ABCB11 gene mutations in the patient, i.e. I498T and
      2098delA. The correlation of the patient's genotypes with the clinical course
      supports the existence of a phenotypic continuum between BRIC2 and PFIC2.

PMID- 16290311
TI  - Induction of angiopoietin-2 gene expression by COX-2: a novel role for COX-2
      inhibitors during hepatocarcinogenesis.

PMID- 16290312
TI  - IGF-I protects cortical neurons against ceramide-induced apoptosis via activation
      of the PI-3K/Akt and ERK pathways; is this protection independent of CREB and Bcl
      2?
AB  - Current understanding of IGF-I-mediated neuroprotection implies the activation of
      phosphatidylinositol-3-kinase (PI-3K), which leads to the activation of
      Akt/Protein Kinase B. In non-neuronal cells, Akt phosphorylates and activates the
      transcription factor CREB, implicated in the transcription of the anti-apoptotic
      bcl-2 gene. This paper further analyses the anti-apoptotic IGF-I action in
      neurons. We show that IGF-I protects cortical neurons against ceramide-induced
      apoptosis. Ceramide decreases Akt phosphorylation during apoptotic process
      whereas a simultaneous treatment with IGF-I increases Akt phosphorylation.
      Analysis of the signal transduction pathways revealed that IGF-I induces CREB
      phosphorylation via PI-3K and ERK, whereas simultaneous ceramide and IGF-I
      treatment decreases CREB phosphorylation. Although an overexpression of Bcl-2
      protects cortical neurons against ceramide-induced apoptosis, our data indicate
      that the Bcl-2 protein level is not modulated during IGF-I, ceramide and/or
      LY294002 treatment. In consequence, we demonstrated that IGF protects neurons
      against ceramide-induced apoptosis and that IGF-I protection involves the PI
      3K/Akt and ERK pathways; this protection may be independent of CREB and Bcl-2.

PMID- 16290313
TI  - Concentration dependent transport of colloids in saturated porous media.
AB  - A series of column experiments was undertaken to explore the influence of colloid
      input concentration (2, 1, 0.5, and 0.25 times a reference concentration),
      colloid size (negatively charged 3.2 and 1.0 microm carboxyl latex), and sand
      grain size (360, 240, and 150 microm quartz sands) on transport and deposition. A
      similar mass of stable mono-dispersed colloids was added to each column. For a
      given input concentration, decreasing the sand size and increasing the colloid
      size resulted in increased mass retention in the sand near the column inlet and
      lower relative concentrations in the effluent. For a given sand and colloid,
      increasing the input concentration produced less deposition and higher mass
      recovery in the effluent, especially for coarser sands and smaller colloids.
      Results of a time dependent attachment (blocking) and detachment model were not
      consistent with this behavior because the simulations predicted much less
      retention near the column inlet and a decreasing number of favorable attachment
      sites (mass of deposited colloids) with increasing input concentration in a given
      system (colloid and sand). A time dependent straining model (filling of straining
      sites) provided a better description of the effluent and deposition data, but
      still could not account for the observed concentration dependent mass recovery.
      Alternatively, the straining model was refined to include a liberation term that
      assumed that straining was hindered at higher concentrations (collision
      frequencies) due to repulsive colloid (aqueous phase)-colloid (strained)
      interactions. Simulations that included straining, liberation, attachment, and
      detachment significantly improved the description of the experimental data.

PMID- 16290314
TI  - Can soaps act as fomites in hospitals?

PMID- 16290315
TI  - Rapid method for the sensitive detection of protein contamination on surgical
      instruments.
AB  - Hospital sterile service departments (SSDs) currently rely on simple visual
      confirmation of cleanliness as an assessment of the efficacy of cleaning surgical
      instruments. The inherent inability to monitor low levels of infectious or
      proteinaceous contamination on surgical instruments creates the possibility that
      highly dangerous and robust biological agents may remain infectious and
      undetected even after standard cleaning and sterilization procedures have been
      employed. This paper describes the development of a novel microscopy technique,
      episcopic differential interference contrast microscope, combined with the
      fluorescent reagent, SYPRO Ruby, to rapidly detect brain tissue protein to below
      400 pg/mm(2) on an instrument surface. This technique has displayed a minimum
      level of detection observed by 50% of volunteers of 85 pg/mm(2) (95% confidence
      intervals 67-112 pg/mm(2)). Quantitative assessment of instruments supplied from
      various SSDs enabled the establishment of a 'contamination index' of both
      proteinaceous and non-proteinaceous deposits on the surface. This new methodology
      for the assessment of surface contamination is generally applicable and should
      facilitate future quantitative surveys of instrument contamination in hospitals
      and other healthcare environments.

PMID- 16290316
TI  - Nosocomial meningitis in a university hospital between 1993 and 2002.
AB  - The aim of this study was to establish the relationship between nosocomial
      meningitis (NM) and surgical interventions, type of pathogens and other hospital
      infections (HIs). Fifty-one patients diagnosed with NM, according to the criteria
      of the Centers for Disease Control and Prevention, in the Neurosurgery Department
      of Ibn-i Sina Hospital of Ankara University between 1993 and 2002 were evaluated
      retrospectively. All individuals with NM were hospitalized in the intensive care
      unit. Third-generation cephalosporins were used for surgical prophylaxis and
      broad-spectrum antibiotics were used for treatment. NM occurred in 0.34% of all
      admissions and accounted for 0.53% of all HIs. Fourteen cases (28%) had at least
      one concurrent HI, mainly originating from surgical wounds and related secondary
      bacteraemia. Four cases had NM following surgical site infection with the same
      causative agent and three cases had bacteraemia. All the individuals had surgical
      interventions and 26 (51%) had operations concerning ventriculoperitoneal shunt.
      A positive microbiological cause was found in the cerebrospinal fluid of 49
      patients, with 16 cases having a polymicrobial cause. Of all 67 micro-organisms
      isolated, 41 (61%) were Gram-negative bacilli, 23 (34%) were Gram-positive cocci
      and the remaining three (5%) were Candida spp. Staphylococci were the most common
      pathogens (30%), followed by non-fermentative Gram-negative bacilli (22%).

PMID- 16290317
TI  - Correlation between the genetic diversity of nosocomial pathogens and their
      survival time in intensive care units.
AB  - Bacteria differ in their ability to survive in the hospital environment outside
      the human host. Species remaining viable and infectious have a higher chance of
      being transmitted, giving them a fitness advantage in hospitals. This
      differential fitness could be expected to alter the genetic population structure
      of bacterial populations in hospitals, and should be reflected by the relative
      abundance of several successful clones. The objective of this study was to test
      for a potential correlation between tenacity, i.e. environmental survival, and
      clonal abundance determined by the genetic diversity in different bacterial
      species from prospectively collected isolates of intensive care patients. A
      literature review was performed to identify mean environmental survival times for
      the most important pathogens in intensive care units (ICUs): Staphylococcus
      aureus, enterococci, Acetinobacter baumannii, Pseudomonas aeruginosa,
      Enterobacter spp., Escherichia coli, Klebsiella pneumoniae and Stenotrophomonas
      maltophilia. To determine the genetic diversity of the natural population of
      these species in ICUs, a prospective 18-month study was conducted in five units
      with median nosocomial infection rates. All clinical isolates were collected, and
      highly discriminatory DNA fingerprinting techniques were used to identify
      specific clones. A diversity index for each species was calculated as the number
      of distinguishable genotypes in the population divided by size. The correlation
      between survival times and the diversity indices for the individual pathogens was
      investigated using non-parametric methods. Although 21 studies were identified in
      the literature, only two were relevant. They showed median survival times between
      1.5 days (P. aeruginosa) and 60.0 days (Enterococcus faecium). During the
      prospective ICU study, 1264 pathogens were investigated and simple diversity
      indices between 49.1 (Enterococcus faecalis) and 89.8 (E. coli) were found. A
      correlation between survival times and the diversity indices for the individual
      pathogens was found (correlation coefficient 0.821, P=0.024). Environmental
      survival may be an important factor contributing to the ecological fitness of
      some nosocomial pathogens in ICUs. Infection control measures should consider
      this finding.

PMID- 16290318
TI  - Bacterial contamination of computers and telephones in a university hospital in
      Turkey.

PMID- 16290319
TI  - Environmental reservoirs of methicillin-resistant Staphylococcus aureus in
      isolation rooms: correlation with patient isolates and implications for hospital
      hygiene.
AB  - Strategies to control and prevent the spread of methicillin-resistant
      Staphylococcus aureus (MRSA) include early identification of positive patients
      through screening, patient isolation, hand hygiene, nasal and skin
      decontamination, and the adequate cleaning and decontamination of clinical areas.
      However, many national and other guidelines provide few details on environmental
      decontamination regimens, partly because the role of the environment in the
      spread of MRSA is not well documented. We prospectively studied the environment
      of the isolation rooms of 25 MRSA patients for up to four weeks, sampling
      horizontal surfaces and the air using settle plates as well as an air sampler,
      while continuing regular daily cleaning according to the hospital protocol. We
      then typed 20 patient isolates and the corresponding environmental isolates
      (N=35) to assess the similarity of strains. A high proportion of samples were
      positive for MRSA; 269/502 (53.6%) surface samples, 70/250 (28%) air samples and
      102/251 (40.6%) settle plates. Over half of the surface samples taken from the
      beds and the mattresses were positive for MRSA. Identical or closely related
      isolates were recovered from the patient and their environment in 14 (70%)
      patients, suggesting possible environmental contamination of the isolation rooms,
      possibly contributing to endemic MRSA. More effective and rigorous use of current
      approaches to cleaning and decontamination is required as well as consideration
      of newer technologies to eradicate MRSA and other hospital-acquired pathogens.

PMID- 16290320
TI  - Melanocortin-4 receptors, beta-MSH and leptin: key elements in the satiety
      pathway.
AB  - This paper reviews aspects of our research, focusing on the role of the
      melanocortin system in the central regulation of feeding and energy balance,
      which was begun in 1997. It describes data from successive physiological studies,
      concerning the identity of the appetite-regulating melanocortin receptor,
      melanocortin-4 receptor (MC4R) regulation with altered nutritional status, the
      role of MC4R in dietary obesity and the identity of the endogenous MC4R ligand.

PMID- 16290321
TI  - Depletion of reduced glutathione precedes inactivation of mitochondrial enzymes
      following limbic status epilepticus in the rat hippocampus.
AB  - The time course and critical determinants of mitochondrial dysfunction and
      oxidative stress following limbic status epilepticus (SE) were investigated in
      hippocampal sub-regions of an electrical stimulation model in rats, at time
      points 4-44h after status. Mitochondrial and cytosolic enzyme activities were
      measured spectrophotometrically, and reduced glutathione (GSH) concentrations by
      HPLC, and compared to results from sham controls. The earliest change in any sub
      region was a fall in GSH, appearing as early as 4h in CA3 (-13%, p<0.05), and
      persisting at all time points. This was followed by a transient fall in complex I
      activity (CA3, 16h, -13%, p<0.05), and later changes in aconitase (CA1,-18% and
      CA3, -22% at 44h, p<0.05). The activity of the cytosolic enzyme glyceraldehyde-3
      phosphate-dehydrogenase was unaffected at all time points. It is known that GSH
      levels are dependent both on redox status, and on the availability of the
      precursor cysteine, in turn dependent on the cysteine/glutamate antiporter, for
      which extracellular glutamate concentrations are rate limiting. Both mechanisms
      are likely to contribute indirectly to GSH depletion following seizures. That a
      relative deficiency in GSH precedes later changes in the activities of complex I
      and aconitase in vulnerable hippocampal sub-regions, occurring within a
      clinically relevant therapeutic time window, suggests that strategies to boost
      GSH levels and/or otherwise reduce oxidative stress following seizures, deserve
      further study, both in terms of preventing the biochemical consequences of SE and
      the neuronal dysfunction and clinical consequences.

PMID- 16290322
TI  - 5-HT uptake blockade prevents the increasing effect of K(ATP) channel blockers on
      electrically evoked [3H]-5-HT release in rat and mouse neocortical slices.
AB  - To explore if prolonged--as opposed to acute--5-HT uptake blockade can lead to
      changes in the function of ATP-dependent potassium (K(ATP)) channels, we
      investigated in rat and mouse neocortical slices the effects of K(ATP) channel
      blockers on electrically evoked [3H]-serotonin ([3H]-5-HT) release after short-
      and long-term exposure to 5-HT uptake blockers. Glibenclamide (1 microM), a
      K(ATP) channel blocker, enhanced the electrically evoked [3H]-5-HT release by 66
      and by 77%, respectively, in rat and in mouse neocortex slices. This effect was
      confirmed in the rat by tolbutamide (1 microM), another K(ATP) channel
      antagonist. After short-term blockade (45 min) of 5-HT uptake, glibenclamide
      still increased the release of [3H]-5-HT in the rat. Glibenclamide, however,
      failed to enhance [3H]-5-HT release after long-term uptake blockade (210 min). In
      the mouse, however, both short- and long-term inhibition of 5-HT reuptake by
      citalopram (1 microM) prevented the facilitatory effect of glibenclamide. The
      Na(+)/K(+)-ATPase inhibitor ouabain (3.2 microM) abolished the glibenclamide
      induced increase in [3H]-5-HT release in both rat and mouse, suggesting that an
      operative Na(+)/K(+)-ATPase is a prerequisite for activation of K(ATP) channels.
      The terminal 5-HT(1B) autoreceptor-mediated feedback control was involved in the
      glibenclamide-induced increase in [(3)H]-5-HT release only in mouse neocortical
      tissue, as evident from the use of the 5-HT(1B) autoreceptor ligands metitepin (1
      microM) and cyanopindolol (1 microM). These results suggest that in the rat long
      term uptake blockade leads to an impaired activity of the Na(+)/K(+)-ATPase,
      which increases intracellular ATP and consequently closes K(ATP) channels. In the
      mouse, however, short-term uptake blockade seems to already reduce the activity
      of the Na(+)/K(+)-ATPase and thereby the consumption of ATP. Blockade of 5-HT
      transporters thus may close K(ATP) channels through increased intracellular ATP.
      The following slight depolarisation seems to facilitate 5-HT release. These
      results may contribute to a better understanding of the mechanisms involved in
      the clinical time latency of antidepressant efficacy of monoamine uptake
      blockers.

PMID- 16290324
TI  - Nursing and the philosophy of science. 1991.

PMID- 16290323
TI  - Determining the oxidation states of manganese in NT2 cells and cultured
      astrocytes.
AB  - Excessive brain manganese (Mn) can produce a syndrome called "manganism", which
      correlates with loss of striatal dopamine and cell death in the striatum and
      globus pallidus. The prevalent hypothesis for the cause of this syndrome has been
      oxidation of cell components by the strong oxidizing agent, Mn(3+), either formed
      by oxidation of intracellular Mn(2+) or transported into the cell as Mn(3+). We
      have recently used X-ray absorption near edge structure spectroscopy (XANES) to
      determine the oxidation states of manganese complexes in brain and liver
      mitochondria and in nerve growth factor (NGF)-induced and non-induced PC12 cells.
      No evidence was found for stabilization or accumulation of Mn(3+) complexes
      because of oxidation of Mn(2+) by reactive oxygen species in these tissues. Here
      we extend these studies of manganese oxidation state to cells of brain origin,
      human neuroteratocarcinoma (NT2) cells and primary cultures of rat astrocytes.
      Again we find no evidence for stabilization or accumulation of any Mn(3+) complex
      derived from oxidation of Mn(2+) under a range of conditions.

PMID- 16290325
TI  - International nursing students: a phenomenological perspective. 2003.

PMID- 16290326
TI  - Students' evolving beliefs about nursing: from entry to graduation in a four-year
      baccalaureate programme. 1995.

PMID- 16290327
TI  - The pure and the applied in nursing education. 2000.

PMID- 16290329
TI  - Importance of micellar kinetics in relation to technological processes.
AB  - The association of many classes of surface-active molecules into micellar
      aggregates is a well-known phenomenon. Micelles are in dynamic equilibrium,
      constantly disintegrating and reforming. This relaxation process is characterized
      by the slow micellar relaxation time constant, tau(2), which is directly related
      to the micellar stability. Theories of the kinetics of micelle formation and
      disintegration have been discussed to identify the gaps in our complete
      understanding of this kinetic process. The micellar stability of sodium dodecyl
      sulfate micelles has been shown to significantly influence technological
      processes involving a rapid increase in interfacial area, such as foaming,
      wetting, emulsification, solubilization, and detergency. First, the available
      monomers adsorb onto the freshly created interface. Then, additional monomers
      must be provided by the breakup of micelles. Especially when the free monomer
      concentration is low, which is the case for many nonionic surfactant solutions,
      the micellar breakup time is a rate-limiting step in the supply of monomers. The
      Center for Surface Science & Engineering at the University of Florida has
      developed methods using stopped flow and pressure jump with optical detection to
      determine the slow relaxation time of micelles of nonionic surfactants. The
      results showed that the ionic surfactants such as SDS exhibit slow relaxation
      times in the range from milliseconds to seconds, whereas nonionic surfactants
      exhibit slow relaxation times in the range from seconds (for Triton X-100) to
      minutes (for polyoxyethylene alkyl ethers). The slow relaxation times are much
      longer for nonionic surfactants than for ionic surfactants, because of the
      absence of ionic repulsion between the head groups. The observed relaxation times
      showed a direct correlation with dynamic surface tension and foaming experiments.
      In conclusion, relaxation time data of surfactant solutions correlate with the
      dynamic properties of the micellar solutions. Moreover, the results suggest that
      appropriate micelles with specific stability or tau(2) can be designed by
      controlling the surfactant structure, concentration, and physicochemical
      conditions (e.g., salt concentration, temperature, and pressure). One can also
      tailor micelles by mixing anionic/cationic or ionic/nonionic surfactants for a
      desired stability to control various technological processes.

PMID- 16290328
TI  - A model for short alpha-neurotoxin bound to nicotinic acetylcholine receptor from
      Torpedo californica: comparison with long-chain alpha-neurotoxins and alpha
      conotoxins.
AB  - Short-chain alpha-neurotoxins from snakes are highly selective antagonists of the
      muscle-type nicotinic acetylcholine receptors (nAChR). Although their spatial
      structures are known and abundant information on topology of binding to nAChR is
      obtained by labeling and mutagenesis studies, the accurate structure of the
      complex is not yet known. Here, we present a model for a short alpha-neurotoxin,
      neurotoxin II from Naja oxiana (NTII), bound to Torpedo californica nAChR. It was
      built by comparative modeling, docking and molecular dynamics using 1H NMR
      structure of NTII, cross-linking and mutagenesis data, cryoelectron microscopy
      structure of Torpedo marmorata nAChR [Unwin, N., 2005. Refined structure of the
      nicotinic acetylcholine receptor at 4A resolution. J. Mol. Biol. 346, 967-989]
      and X-ray structures of acetylcholine-binding protein (AChBP) with agonists
      [Celie, P.H., van Rossum-Fikkert, S.E., van Dijk, W.J., Brejc, K., Smit, A.B.,
      Sixma, T.K., 2004. Nicotine and carbamylcholine binding to nicotinic
      acetylcholine receptors as studied in AChBP crystal structures. Neuron 41 (6),
      907-914] and antagonists: alpha-cobratoxin, a long-chain alpha-neurotoxin
      [Bourne, Y., Talley, T.T., Hansen, S.B., Taylor, P., Marchot, P., 2005. Crystal
      structure of Cbtx-AChBP complex reveals essential interactions between snake
      alpha-neurotoxins and nicotinic receptors. EMBO J. 24 (8), 1512-1522] and alpha
      conotoxin [Celie, P.H., Kasheverov, I.E., Mordvintsev, D.Y., Hogg, R.C., van
      Nierop, P., van Elk, R., van Rossum-Fikkert, S.E., Zhmak, M.N., Bertrand, D.,
      Tsetlin, V., Sixma, T.K., Smit, A.B., 2005. Crystal structure of nicotinic
      acetylcholine receptor homolog AChBP in complex with an alpha-conotoxin PnIA
      variant. Nat. Struct. Mol. Biol. 12 (7), 582-588]. In complex with the receptor,
      NTII was located at about 30 A from the membrane surface, the tip of its loop II
      plunges into the ligand-binding pocket between the alpha/gamma or alpha/delta
      nAChR subunits, while the loops I and III contact nAChR by their tips only in a
      'surface-touch' manner. The toxin structure undergoes some changes during the
      final complex formation (for 1.45 rmsd in 15-25 ps according to AMBER'99
      molecular dynamics simulation), which correlates with NMR data. The data on the
      mobility and accessibility of spin- and fluorescence labels in free and bound
      NTII were used in MD simulations. The binding process is dependent on spontaneous
      outward movement of the C-loop earlier found in the AChBP complexes with alpha
      cobratoxin and alpha-conotoxin. Among common features in binding of short- and
      long alpha-neurotoxins is the rearrangement of aromatic residues in the binding
      pocket not observed for alpha-conotoxin binding. Being in general very similar,
      the binding modes of short- and long alpha-neurotoxins differ in the ways of loop
      II entry into nAChR.

PMID- 16290330
TI  - Adsorption study of cationic dyes having a trimethylammonium anchor group on
      hectorite using electrooptic and spectroscopic methods.
AB  - Clay minerals are natural or synthetic material of colloidal dimensions. Due to
      the sheetlike structure clay minerals offer a huge specific surface area and
      hence optimal properties for modification through adsorption. The current work
      studies the adsorption of five cationic dyes on the synthetic clay mineral
      hectorite. All dyes have a trimethylammonium anchoring group in common. The
      adsorbed dye molecules are characterized by means of pulsed electric linear
      dichroism and UV-VIS spectroscopy. With increasing dye loading a continuous shift
      in the absorption spectra is observed. But there is no occurrence of a new
      absorption band. Therefore we conclude that the dyes preferentially adsorb as
      amorphous aggregates on the clay surface. At low dye loadings the dye molecules
      lie flat on the clay mineral surface. Increasing dye concentration leads to a
      continuous increase in average tilt angle. However the orientation of the dye
      molecules is very sensitive to functional groups. The introduction of a nitro
      group to a particular dye increases significantly the tendency to lie flat on the
      surface whereas the introduction of a methoxy group at the same position has the
      opposite effect.

PMID- 16290331
TI  - Copper sorption on a straw lignin: experiments and EPR characterization.
AB  - Spectroscopic and physicochemical data, X-ray photoelectron spectroscopy (XPS),
      solid-state (13)C cross-polarization magic-angle-spinning NMR, GC/MS, specific
      surface area, site density, and surface acidity constants have been recorded or
      determined for a ligno-cellulosic substrate (LS) extracted from straw. Its
      copper(II)-bound ability has also been studied. The LS solid that exhibits two
      types of binding sites, carboxylic and phenolic groups, has a great affinity for
      copper(II), with a maximum of adsorption at around 4 mg g(-1) as early as the pH
      reaches 6. The structural characterization of the Cu(II) surface complexes has
      been investigated using EPR spectroscopy. The CuO(4) chromophore of the inner
      sphere surface complexes is a slightly distorted square. A surface oxidation
      occurred simultaneously, which leads to semiquinonic radicals. Furthermore, our
      empirical approach, which used a correlation between thermodynamics data and EPR
      parameters, has led to a surface complexation constant log beta equal to 12.6.
      This indicates that copper(II) surface complexes are relatively stable.

PMID- 16290332
TI  - Strontium adsorption properties of an aluminum-pillared montmorillonite carrying
      carboxylate functional groups.
AB  - Strontium adsorption was studied in an aluminum-pillared montmorillonite (PILC)
      carrying organic acid groups. The in situ dissociation of these groups increases
      the number of negative sites in the modified PILC, promoting thus the uptake of
      cations from an exchange solution. To investigate the role of solution pH and
      acid strength in cation uptake phenomena, base titrations were performed for
      PILCs carrying either oxalate or acetate groups. Comparison with the pristine
      PILC showed that extra Sr(2+) uptake initiated at pH 6 and 8 in the presence of
      oxalate and acetate, respectively. The overall increase in Sr(2+) uptake was
      higher in the presence of oxalate and amounted to about 136% as compared with the
      pristine PILC, at pH slightly above 8. The effect of the acid's strength was
      further probed through strontium adsorption isotherms, taken at a constant pH for
      PILC samples carrying acetate, oxalate, malonate, or citrate groups. The results
      demonstrate that cation uptake can be optimized by tuning the pH conditions to
      the acid's strength or vice versa.

PMID- 16290333
TI  - Insights into electrodeposition of an inhibitor film and its inhibitive effects
      on calcium carbonate deposition.
AB  - Polycarboxylic acid (PAA), a common scale inhibitor has demonstrated adsorption
      properties on stainless steel surfaces. An electrochemically based technique has
      been used to assess the extent of film formation. The presence of calcium and
      magnesium ions in the solution and the cathodic electrochemical activity at the
      metal surface have been shown to enhance the inhibitor film formation by
      promoting the transport of the inhibitor from the solution to the metal surface.
      The effect of the inhibitor film in retarding scale deposition is assessed using
      measurement of the deposition onto metal electrodes immersed in a supersaturated
      solution of CaCO(3). The practical implications of these findings are discussed.

PMID- 16290334
TI  - Adsorption behavior of methylene blue and its congeners on a stainless steel
      surface.
AB  - Methylene blue and its congeners as model dyes were adsorbed onto stainless steel
      particles at different ionic strengths, pH values, and ethanol contents, and the
      adsorption mechanism was investigated. A Fourier transform infrared spectroscopy
      (FTIR) analysis of the dyes adsorbed on the stainless steel plate was carried out
      to determine the orientations of the adsorbed dyes on stainless steel surface.
      The adsorption isotherms for all the dyes tested were approximated by a Langmuir
      equation (Q=Kq(m)C/(1+KC)) in most cases except under strongly basic conditions.
      From the ionic strength and ethanol content dependencies of the K value in the
      Langmuir equations, both the electrostatic and hydrophobic interactions were
      indicated to contribute to the adsorption of the dyes at neutral pH. By comparing
      the K and q(m) values for the methylene blue congeners and with the aid of the
      FTIR analyses, it was found that the kind of substituent groups at most positions
      of the polyheterocycles of methylene blue strongly affects the adsorption
      behavior, particularly the area occupied by an adsorbed dye molecule, the
      affinity for the stainless steel surface, and the orientation of the adsorbed dye
      molecule on the stainless steel surface.

PMID- 16290335
TI  - Preparation of amorphous aluminum oxide-hydroxide nanoparticles in amphiphilic
      silicone-based copolymer microemulsions.
AB  - Organo-inorgano nanocomposites with colloidal dimensions have interesting
      optical, catalytic, and mechanical properties, particularly when such hybrids are
      reinforced with transition metal oxide nanoparticles. Nanoparticles with a mean
      size of 1.0-2.4 nm are obtained through hydrolysis of aluminum isopropoxide in
      the L(2) phase of amphiphilic (PDMS-POE) polydimethylsiloxane-polyoxyethylene
      Silwet L-7607-octanol/acetylacetone-water mixtures. The particle sizes are
      related weakly to the microemulsion composition: 0.8-1.2 nm for 20 wt% Silwet L
      7607 and 2.0-2.4 nm for 50 wt% Silwet L-7607. Protection of the particles against
      aggregation is ensured through their confinement in the intraaggregate colloidal
      domains. Factors affecting the hydrolysis-condensation process of acetylacetone
      complexed aluminum isopropoxide in copolymer-poor and copolymer-rich regions of
      PDMS-POE W/O microemulsions are studied by Fourier transform infrared
      spectroscopy, small angle X-ray scattering, and transmission electron microscopy.
      Prepared nanoparticulate dispersions possess long-term stability and form clear
      mixtures in different organic polar and nonpolar solvents.

PMID- 16290336
TI  - Characterization of nanostructured hollow polymer spheres with small-angle
      neutron scattering (SANS).
AB  - Hollow polymer spheres synthesized from a vesicle-directed polymerization can be
      dried and redispersed in water using a variety of nonionic ethoxylated alcohol
      surfactants as stabilizers. The final dispersions consist of both polymer shells
      and surfactant micelles, which remain together in colloidal suspension for at
      least several months. Small-angle neutron scattering (SANS) is used to measure
      the polymer shell thickness (63 A) and core radius (560 A) of the surfactant
      stabilized hollow polymer spheres in the presence of surfactant micelles.
      Characterization by SANS provides information about the surfactant bilayer and
      polymer shell thicknesses which were previously unattainable.

PMID- 16290337
TI  - Confocal microscopy of a dense particle system.
AB  - We report experiments utilizing confocal microscopy to determine the position of
      cornflour starch granules in a paste, as a function of distance from a wall. The
      granules have an average diameter of 15 mum. If a solvent is chosen such as to
      approximately match the refractive index of the granules then images of them can
      be obtained to a depth of 120 mum, which is the limit imposed by the working
      distance of the x 40 oil immersion lens used in the experiment. An algorithm is
      presented which successfully identifies the particle centers in 3D. In addition
      to experiments on static systems we show how measurements of particle number
      density and velocity can be obtained from images of a system in pipe flow. We
      find that particles are depleted from the wall over a range of around 100 mum.

PMID- 16290338
TI  - A direct measurement of the ion-exchange capacity of muscovite mica using a
      mettler ultramicrobalance.
AB  - A direct method is described of measuring the mass of substances dissolved from
      muscovite mica in water. The mica sheets are weighed by the use of a Mettler
      ultramicrobalance both before and after the immersion in water. The decrease in
      weight is regarded as identical to the dissolved mass. An analysis by ICP-AES has
      confirmed that the dissolution is due to an ion exchange of metal ions, mainly
      potassium ions. As a result of the measurement of the change in weight of mica
      sheets with immersion time, it has been found that it takes about 30 min to
      finish the dissolution. The total mass dissolved from basal plane has been
      determined irrespective of the difference in fraction of metal ions shared with
      each of the two mica surfaces obtained by cleavage along the basal plane. The
      measured values of the total mass differ from specimen to specimen and fall in
      the range from 1 to 10 mg m(-2). These values of the dissolved mass are
      comparable to the order of 10 monolayers of potassium ions included in basal
      plane. The present result suggests that internal metal ions as well as external
      ions contribute to the ion exchange occurring on the surface of muscovite mica.

PMID- 16290339
TI  - Aging effects in the electrokinetics of colloidal iron oxides.
AB  - We analyze in this contribution the effect of aging on the electrokinetic
      properties of magnetite (Fe(3)O(4)) and hematite (alpha-Fe(2)O(3)). In both
      cases, high-purity commercial samples and monodisperse synthetic particles were
      studied. Commercial magnetite showed a rather erratic dependence of its
      electrophoretic mobility u(e) with the concentration of NaCl. Furthermore,
      sufficient concentrations of the latter were able to change the sign of the
      mobility. When KNO(3) solutions were used, although no such change was observed,
      no clear effect of [KNO(3)] on the mobility was found, and, in addition, an
      intense aging effect was detected, as the mobility became increasingly positive
      in suspensions that were stored over 1 day. The picture was radically different
      with synthetic magnetite spheres, as the expected overall decrease of u(e) with
      either NaCl or KNO(3) concentration was measured. However, also in this case the
      aging effect was clearly observed: u(e) tended in this case to more negative
      values upon suspension storage, and a steady value of the mobility was reached
      only after 5 days in NaCl (and even longer in KNO(3) solutions). Because of the
      crystal structure similarities between magnetite and maghemite (gamma-Fe(2)O(3)),
      it has been shown that the final step of magnetite oxidation is maghemite. This
      is confirmed in the present study, as the mobility-pH trends of magnetite
      progressively approach those of maghemite after about 7 days of storage. Since
      hematite is chemically more stable than magnetite, our study focused in this case
      on the comparison between commercial and synthetic particles. The former showed a
      negative mobility at pH 5.5 under all conditions, suggesting an isoelectric point
      well below the value accepted for hematite (>/=7). The effect of aging on
      commercial samples was again very significant, as u(e) decreased in absolute
      value, apparently without limit as the time since preparation was longer. In
      contrast, synthetic hematite showed a more predictable dependence on ionic
      strength, and more limited aging effects, as u(e) reached equilibrium values
      after around 5 days in NaCl; longer times were required in KNO(3) solutions.

PMID- 16290340
TI  - XPS and wettability characterization of modified poly(lactic acid) and
      poly(lactic/glycolic acid) films.
AB  - Poly(lactic acid) (PLA) and poly(lactic/glycolic acid) copolymers (PLGA) are
      biodegradable drug carriers of great importance, although successful
      pharmaceutical application requires adjustment of the surface properties of the
      polymeric drug delivery system to be compatible with the biological environment.
      For that reason, reduction of the original hydrophobicity of the PLA or PLGA
      surfaces was performed by applying a hydrophilic polymer poly(ethylene oxide)
      (PEO) with the aim to improve biocompatibility of the original polymer. PEO
      containing surfaces were prepared by incorporation of block copolymeric
      surfactants, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)
      (Pluronic), into the hydrophobic surface. Films of polymer blends from PLA or
      PLGA (with lactic/glycolic acid ratios of 75/25 and 50/50) and from Pluronics
      (PE6800, PE6400, and PE6100) were obtained by the solvent casting method,
      applying the Pluronics at different concentrations between 1 and 9.1% w/w.
      Wettability was measured to monitor the change in surface hydrophobicity, while X
      ray photoelectron spectroscopy (XPS) was applied to determine the composition and
      chemical structure of the polymer surface and its change with surface
      modification. Substantial reduction of surface hydrophobicity was achieved on
      both the PLA homopolymer and the PLGA copolymers by applying the Pluronics at
      various concentrations. In accordance with the wettability changes the
      accumulation of Pluronics in the surface layer was greatly affected by the
      initial hydrophobicity of the polymer, namely, by the lactide content of the
      copolymer. The extent of surface modification was also found to be dependent on
      the type of blended Pluronics. Surface activity of the modifying Pluronic
      component was interpreted by using the solubility parameters.

PMID- 16290341
TI  - Creation of ordered patterns by dewetting of thin films on homogeneous and
      heterogeneous substrates.
AB  - Spontaneous formation of locally ordered patterns during dewetting of thin films
      on homogeneous and heterogeneous substrates is investigated based on the 3-D
      nonlinear equation of motion. Physicochemical heterogeneities engender the rapid
      formation of the primary holes that serve as "seeds" for the formation of locally
      ordered structures. The secondary multiring structure surrounding the primary
      hole evolves by one of the following two different pathways depending on the film
      thickness vis-a-vis the location of the minimum in the spinodal curve: (A) Thick
      films evolve by the formation of secondary satellite holes that originate from a
      ring-like depression behind the rim of the primary hole. The process of ordering
      is repeated until the true spinodal holes appear on the remaining substrate. (B)
      Ordering in a relatively thin film occurs by the formation of droplets caused by
      the disintegration of the elevated rim that surrounds the primary hole. The
      radial distance between the successive ordered layers is close to the spinodal
      length scale, lambda(m). Droplets within the same layer are separated by a
      distance slightly greater than lambda(m), whereas holes within the same layer are
      separated by a distance slightly less than lambda(m). The number density of holes
      or droplets in the ordered pattern is of the same order as the predictions of the
      spinodal theory. The number of ordered layers and the size of the locally ordered
      domain depend significantly on the relative magnitudes of the time scales for the
      following events: (1) formation of the primary hole, (2) growth of holes (inverse
      of hole-growth velocity), (3) formation of a secondary feature (hole or droplet)
      adjacent to the primary hole, (4) true spinodal rupture far from the primary
      hole. The morphology of an ordered structure can therefore be tailored by
      modulation of the film thickness and the short- and long-range intermolecular
      interactions (substrate surface properties), since these affect the time scales 1
      to 4 in different ways.

PMID- 16290343
TI  - Intercalation of octadecylamine into montmorillonite: molecular simulations and
      XRD analysis.
AB  - Intercalation of octadecylamine (ODAMIN) into Na montmorillonite based on the ion
      dipole interaction was investigated using molecular mechanics and molecular
      dynamics simulations combined with X-ray powder diffraction. Molecular modeling
      revealed the interlayer structure of the ODAMIN-montmorillonite intercalate, the
      charge distribution on the host layer and guest species, and the energy
      characteristics, i.e., the total sublimation energy and it's individual
      contributions (electrostatic and Van der Waals). The present study showed the
      development of the interlayer structure, basal spacing, and exfoliation energy in
      dependence on the ODAMIN content.

PMID- 16290342
TI  - Adsorption and kinetic studies of the intercalation of some organic compounds
      onto Na+-montmorillonite.
AB  - The adsorption and the kinetics of the intercalation of metanil yellow dye, p
      aminodiphenylamine (p-NH(2)-DPA), and benzidine by colloidally dispersed Na(+)
      montmorillonte (Na(+)-MMT) have been studied. The adsorption isotherm parameters
      confirmed the occurrence of chemical adsorption that is based on the cation
      exchange process. The selectivity of these compounds toward Na(+)-MMT follows the
      order metanil yellow<p-NH(2)-DPA<benzidine, which reflects the stability sequence
      of the intercalates. The attainment of sorption equilibrium and the diffusion
      coefficient follows the order metanil yellow>p-NH(2)-DPA>benzidine. The rate of
      oxidation has been quantitatively measured using a stopped-flow
      spectrophotometer. The rate constant follows the order benzidine<p-NH(2)
      DPA<metanil yellow. Addition of allyle acetate shows inhibiting effect on the
      reaction rate. The rate of cation exchange process between the radical cation of
      the organic molecule and the Na(+)-ion in the Na(+)-MMT has been monitored by
      using the stopped-flow instrument with an electrical conductivity detection unit.
      The activation energy of the electron transfer reaction is less than that of
      cation exchange process and has the order metanil yellow<p-NH(2)-DPA<benzidine. X
      ray diffraction, IR, and differential scanning colorimetry (DSC) measurements
      confirmed the intercalation process.

PMID- 16290344
TI  - The kinetics of dissolution of the carbonate minerals of phosphate ores using
      dilute acetic acid solutions: the case of pH range from 3.96 to 6.40.
AB  - In this manuscript we present, in detail, the mechanism of the selective
      dissolution of calcite from low-grade phosphate ores (Epirus area, Greece) by
      dilute acetic acid. It was found that mass transfer makes a significant
      contribution to the rate-determining step of the overall reaction of four
      separate pH regions discriminated within the pH range from 3.96 to 6.40.
      Moreover, two different reaction mechanisms were proposed and two different model
      equations best fitted the corresponding experimental data. By applying a
      particular treatment to the developed differential equations proposed by us
      earlier (see Ref. (2)), we estimated the rate constants of specific slow
      reactions referred to pH regions 3.96-4.95 and 4.95-5.50. However, for pH region
      5.50-6.40, we cannot reach a similar conclusion so far.

PMID- 16290345
TI  - A new technique for the measurement of the dynamic evolution of surface tension.
AB  - We develop a novel technique which deduces the surface tension in air of a fluid
      as a function of surface age, beginning at age zero. The technique utilizes
      pointwise measurements of perpendicular free surface profiles of a steady
      oscillating jet corresponding to a discretization interval on the order of 0.1
      ms. We implement the technique on constant-surface-tension test fluids (100%
      ethanol and 15% ethanol/85% water by volume) to demonstrate the extent to which
      the technique can qualitatively capture that the surface tensions of these fluids
      are constant in time, and quantitatively produce values of these constants
      consistent with static measurements. We then implement the technique on jets of
      two agricultural surfactant mixtures, Triton X-405 and Triton X-100, and
      quantitatively deduce the decay of surface tension as a function of surfactant
      concentration.

PMID- 16290346
TI  - Physicochemical investigations of microemulsification of coconut oil and water
      using polyoxyethylene 2-cetyl ether (Brij 52) and isopropanol or ethanol.
AB  - The microemulsification of coconut oil/polyoxyethylene 2-cetyl ether/2-propanol
      or ethanol/water was investigated. The phase behaviors of the mixed system were
      examined. The shear viscosity at different temperatures was measured to derive
      activation parameters for the viscous flow. The diffusion coefficient of the
      microemulsions at different compositions was determined by the DLS method. The
      energetics of solubilization of water into oil + Brij + alkanol as well as of oil
      into water + Brij + alkanol forming w/o and o/w microemulsions, respectively,
      were calorimetrically determined.

PMID- 16290347
TI  - Complex shear modulus of concentrated suspensions of solid spherical particles.
AB  - Starting from the complex shear modulus equation for a dilute suspension system,
      three new equations are developed for the complex shear modulus of concentrated
      suspensions of solid spheres. The continuous phase (matrix) and the dispersed
      particles are treated as viscoelastic materials in the derivation. Complex shear
      modulus data on suspensions of spherical glass beads in polymeric liquid were
      obtained experimentally and compared with the predictions of the proposed
      equations. The proposed equations describe the experimental data reasonably well.

PMID- 16290348
TI  - Batch gravitational sedimentation of slurries.
AB  - We investigated the batch settling behavior of the kaolin slurry and the UK ball
      clay slurry at various initial solids fractions (phi(0)s) using a computerized
      axial tomography scanner (CATSCAN). The spatio-temporal evolutions of solids
      fractions in the consolidating sediments were continuously monitored. Since the
      interface between the sediment and the supernatant of the investigated slurries
      was blurred, an averaging procedure was employed to estimate their null-stress
      solids fractions (phi(g)s). Besides the rather slow settling for the high-phi(0)
      slurries, the basic settling characteristics resemble each other regardless of
      whether phi(0)>phi(g) or vice versa. The above-mentioned experimental data reveal
      that the investigated slurries are neither purely elastic nor purely plastic in
      rheological behavior. On contrary to most model works a blurred supernatant
      sediment interface makes difficulty in the gel point determination. During
      initial settling the high-phi(0) slurries clearly exhibit a finite yield stress
      to resist deformation. That is, the slurries are plastic fluids. However, the
      network structure in the slurries deteriorates gradually in the subsequent
      settling stage while the final, equilibrated sediment reveals a continuous
      distribution in solids fraction. Restated, the final sediment possesses as a
      purely elastic characteristic. The model parameters of theory by Buscall and
      White were regressed by the dynamic consolidating sediment data, while those by
      Tiller and Leu were obtained using the final equilibrated sediment data.
      Calculations from both models reveal that ball clay slurry is more compressible
      than is the kaolin slurry. The high-phi(S0) slurry would yield the less
      compressible sediment.

PMID- 16290349
TI  - Settling and deformation of a thin elastic shell on a thin fluid layer lying on a
      solid surface.
AB  - placement of a soft contact lens onto the cornea, the upper eyelid deforms and
      settles the lens by squeezing fluid out of the post-lens tear film or POLTF
      (i.e., the tear fluid layer sandwiched between the lens and the cornea). This
      paper studies the physical mechanisms that control the dynamic state of the
      contact lens during blinking, i.e., its shape and its distance from the cornea,
      especially a long time after insertion. We model the lens as a deformable elastic
      shell and the cornea as a flat nondeformable body. The tear fluid is assumed to
      be Newtonian, and the lens is characterized by an elastic modulus and a Poisson
      ratio. Lubrication equations under creeping flow are used to solve the fluid
      problem, while the thin-shell approximation is applied to the solid lens. The
      solid and fluid mechanics problems are coupled by maintaining continuity of
      stress and velocity at the solid/liquid interface. Lid applied pressure causes
      the lens to approach the cornea by squeezing tear fluid out and also leads to the
      deformation of the lens. Subsequently, in the interblink period, since there is
      no applied force, the elastic energy stored in the lens due to its deformation is
      released causing it to move away from the cornea by imbibing tear fluid into the
      POLTF. If the POLTF thickness is large, the inward motion of the lens in the
      blink is more than the outward motion during interblink, and this causes the lens
      to settle closer to the cornea. Eventually, there may be a balance of the inward
      motion during the blink and the outward motion during the interblink. If so, the
      lens subsequently exhibits periodic steady-state motion. However, it is also
      possible that a balance of inward and outward motion is never achieved, and the
      lens continues to settle endlessly. If this happens, then the thinfilm
      interactions between the mucin-covered corneal surface and the lens material
      determine whether the lens actually touches the cornea and possibly adheres. Our
      elastohydrodynamic analysis serves as a useful tool to elucidate the effects of
      various lens parameters on the final settled state of the lens. In particular, we
      are concerned about eventual adherence and/or mechanical abrasion to the cornea,
      which is very important to the ocular health of soft contact lens wearers.

PMID- 16290350
TI  - Improved electrorheological effect in polyaniline nanocomposite suspensions.
AB  - We prepared polyaniline (PANI)/clay composites that are composed of both PANI
      clay nanocomposite particles and pure PANI particles. The PANI-clay nanocomposite
      particles were made during the polymerization process, wherein PANI particles are
      attached on the surface of exfoliated clay particles modified by an aminosilane
      group. The PANI/clay composites were used as electrorheological fluids (ERFs) by
      dispersing them in silicon oil. The PANI-clay nanocomposite particles, which can
      form columnar structure under an electric field, strongly enhance the mechanical
      rigidity of the suspensions. The maximum yield stress of the PANI/clay composite
      suspensions (15 wt% in silicon oil) was 1.6 kPa at 3 kV/mm, while that of pure
      PANI was 300 Pa at the same electric field. A mechanism to explain the yield
      behaviors of the PANI-based nanocomposite suspensions is proposed.

PMID- 16290352
TI  - Removal of organic dyes from water by liquid-liquid extraction using reverse
      micelles.
AB  - In the present work, solvent extraction using reverse micelles is proposed for
      the removal of organic dyes from water. In this approach, the dye is solubilized
      in the aqueous core of the reverse micelles, which are present in the organic
      phase. The organic phase is subsequently separated from the aqueous phase leading
      to signifi-cant removal of dye. Experimental results reveal that the
      electrostatic interaction between the oppositely charged surfactant head group
      present in the reverse micelles and the dye molecule plays a key role in the
      separation. The removal of the anionic methyl orange dye from water is carried
      out in the presence of cationic hexadecyltrimethyl ammonium bromide surfactant,
      whereas the removal of the cationic methylene blue dye is carried out in the
      presence of anionic sodium dodecylbenzene sulfonate surfactant. Amyl alcohol is
      used as the solvent. The influence of parameters such as dye concentrations,
      surfactant concentrations, pH, and KCl and NaBr concentrations on the percentage
      removal of dye was studied. The percentage removal of dye is decreased with the
      increase in dye concentration in the feed. The increase in surfactant
      concentration resulted in higher dye removal, because more reverse micelles could
      be hosted in the organic phase. The increase in aqueous phase pH resulted in
      enhanced removal of methyl orange from water, while in the case of methylene blue
      the percentage removal decreased. The increase in KCl and NaBr concentrations
      resulted in decreased percentage removal of methylene blue, whereas the
      percentage removal of methyl orange was increased. The effect of pH and salt
      concentration is explained based on charge transfer mechanism and electrostatic
      interactions and dye-surfactant complex formation.

PMID- 16290351
TI  - Molecular recognition of avidin on biotin-functionalized gold surfaces detected
      by FT-IRRAS and use of metal carbonyl probes.
AB  - Fourier transform infrared reflection-absorption spectroscopy (FT-IRRAS) was
      successively used to monitor the covalent immobilization of biotin molecules onto
      a planar gold substrate covered with a self-assembled monolayer of cystamine and
      to transduce the molecular recognition of avidin and biotin. This detection was
      greatly facilitated and made selective by the labeling of avidin and of biotin
      with various transition metal carbonyl probes. The binding of avidin to the
      surface was optimized by blocking the nonspecific binding sites by adsorption of
      an unrelated protein, bovine serum albumin. This work exemplifies the feasibility
      of detecting biomolecular associations involving molecules of any size at a
      liquid/solid interface by using a simple and accessible surface analysis
      technique.

PMID- 16290353
TI  - Direct measurement of the laplace pressure in a very thin liquid film.
AB  - Meniscus force plays an important part in magnetic storage devices, scanning
      probe microscopy, and micromachines, because the meniscus force increases steeply
      as the clearance between solid surfaces decreases down to submicrometers.
      Recently increased experimental and analytical studies on the subject have been
      published from the point of view of mechanical engineering. Meniscus force is
      generated by the Laplace pressure within the thin liquid film. Investigating the
      Laplace pressure is a direct way to clarify the generation mechanism of meniscus
      force. However, no appropriate measuring method of the Laplace pressure is
      available for a very thin liquid film confined by solid surfaces. This paper
      proposes a simple method of direct measurement of the Laplace pressure for the
      cases. The principle of the measurement method is described. Measurement is
      conducted using the measuring device. Experimental results on the Laplace
      pressure show good agreement with the theoretical predictions.

PMID- 16290355
TI  - IR spectroscopy of N-methylpyrrole adsorbed on oxides--a probe of surface
      acidity.
AB  - IR spectra of N-methylpyrrole (NMP) have been measured following adsorption on,
      and subsequent desorption from, SiO(2), TiO(2), ZrO(2), SiO(2)-Al(2)O(3), H
      mordenite, and sepiolite. Three modes of adsorption have been observed: (i)
      hydrogen bonding to surface hydroxyl groups, (ii) electron transfer at Lewis
      acidic surface sites, and (iii) proton transfer at Bronsted acidic surface sites.
      Protonation of NMP was detected only for adsorption on SiO(2)-Al(2)O(3) and H
      mordenite, indicating the presence of Bronsted acidic sites with pK(a) values </=
      2.90. The results establish that the adsorption of NMP can provide useful
      information regarding the nature of surface acidity on oxides which is
      complementary to that obtained from other probe molecules such as NH(3) and
      pyridine.

PMID- 16290356
TI  - Interaction of bacterial endotoxine (lipopolysaccharide) with latex particles:
      application to latex agglutination immunoassays.
AB  - The latex agglutination immunoassay technique uses polymer colloids as carriers
      for antibodies or antigens to enhance the immunological reaction. In this work,
      the interaction of a lipopolysaccharide (LPS) of Brucella Melitensis with two
      conventional latexes has been studied. Some experiments on the physical
      adsorption of the LPS onto these polystyrene beads have been performed and
      several complexes with different coverage degrees were obtained by modifying the
      incubation conditions. Regarding the application in the development of diagnostic
      test systems, it is advisable to study the latex-LPS complexes from an
      electrokinetic and colloidal stability point of view. The complexes were
      electrokinetically characterized by measuring the electrophoretic mobility under
      different redispersion conditions. The colloidal stability was determined by
      simple turbidity measurements. Experimental and theoretical data have been
      employed to study the molecular disposition of the LPS in the latex particle
      surface to compare with the outer membrane of bacterial cells. Latex complexes
      covered by different LPS amounts showed high colloidal stability and adequate
      immunoreactivity that remains for a long time period.

PMID- 16290357
TI  - Copper adsorption and Si, Al, Ca, Mg, and Na release from clinoptilolite.
AB  - Copper adsorption onto clinoptilolite (natural zeolite), Al/Si dissolution, and
      Mg, Ca, and Na release from the substrate were the subjects of the investigation
      described here. Experimental variables were Cu and electrolyte concentrations and
      solution pH. Copper adsorption was found to increase with increased pH and with
      decreased electrolyte concentration. Large amounts of K were also adsorbed from
      electrolyte. Since solution pH was assumed as a variable, the effects of [H(+)]
      differentiation on Cu adsorption and on Al/Si dissolution were also examined. Al
      dissolution was affected mainly by electrolyte concentration, whereas Si
      dissolution was affected mainly by adsorbed Cu amount. It was assumed that the
      release of Mg, Ca, and Na occurs through ion-exchange reactions with solution
      K(+), because their release is affected more by electrolyte concentration than by
      adsorbed Cu. From the study of FTIR spectra for various samples used in the
      present investigation, we observed that the removal of framework Si/Al shifts the
      band which was attributed to O-T-O stretching vibration toward higher frequency.
      Significant changes were observed for the bands assigned to Si-OH-Al bridges and
      to monomeric and polymeric hydrogen bonds at the region between 3650 and 3200 cm(
      1). It is proposed that the Cu species caused the destruction of H-bonded
      structures, whereas K adsorbed species were located at exchangeable sites after
      an ion-exchange process between K and Ca, Mg, and Na from the zeolite's surface.
      An expansion of the zeolite framework was detected from XRD patterns under acid
      conditions.

PMID- 16290358
TI  - Potentiality of reflectometry for the study of the adsorption on dielectric and
      metal substrates: application to the adsorption of polyvinylimidazole on silica
      and gold.
AB  - Optical fixed-angle reflectometry was examined as a technique to study the
      adsorption of organics (polymers, surfactants) on metallic substrates.
      Calculations were made to evaluate the sensitivity of the method with regard to
      the refractive index and the thickness of the metal and the incidence angle.
      Theoretical results show that Ti, Cr, V, Zr, and gold have an appropriate
      sensitivity for detecting the adsorption accurately. Parallel experiments using
      gold and silica substrates and polyvinylimidazole (PVI) as an organic material
      were carried out. Adsorption measurements as a function of polymer concentration,
      pH, and ionic strength were in accordance with expected trends.

PMID- 16290359
TI  - Gelation of aqueous pectin solutions: a dynamic light scattering study.
AB  - We report the dynamic light scattering study of the gelation of aqueous solutions
      of the biopolymer, pectin, induced by the addition of calcium chloride. The time
      correlation function data are analyzed under the framework of the coupling model.
      As the solution enters the semidilute regime where gelation sets in, the
      relaxation process shows a stretched exponential behavior. The stretching
      exponent decreases and the characteristic time of the stretched exponential
      diverges as the system evolves to a gel. Aqueous pectin solutions in the presence
      of 0.1 M NaCl show similar behavior. Thus, the molecular relaxation modes of
      pectin solutions can be well described by the coupling model.

PMID- 16290360
TI  - Attachment of water-soluble proteins to the surface of (magnetizable)
      phospholipid colloids via NeutrAvidin-derivatized phospholipids.
AB  - The present work describes the incorporation of a functionalized phospholipid
      derivative into the phospholipid bilayer of both classical small unilamellar
      vesicles and recently developed magnetoliposomes, resulting in unique biocolloid
      structures onto which peripheral water-soluble enzymes can be immobilized on the
      surfaces. In the first part of this work, a synthesis protocol is outlined for a
      universal membrane anchor for water-soluble proteins.
      Dioleoylphosphatidylethanolamine-N-dodecanyl was used as the starting lipid
      molecule. After activation of the terminal -COOH group, alpha,omega-diamino
      poly(ethylene glycol), used as a hydrophilic, flexible spacer arm, was coupled
      covalently. Subsequently, NeutrAvidin was bound, after blocking the free -NH(2)
      groups with citraconic anhydride. In the second part, the resulting lipid
      NeutrAvidin derivative was incorporated into small unilamellar vesicles comprised
      of dimyristoylphosphatidylglycerol. FPLC with Superdex 200 as the column matrix
      clearly showed that biotinylated alkaline phosphatase, which served as a
      representative model of water-soluble proteins, was attached to the vesicles.
      Furthermore, magnetoliposomes, constructed of the same type of phospholipid
      molecules, were presented as interesting colloids to assess the degree of enzyme
      immobilization in a rapid and elegant manner. Potential applications that can
      emerge from this study are briefly discussed.

PMID- 16290361
TI  - Investigation of particle interactions in concentrated colloidal suspensions
      using frequency domain photon migration: monodisperse systems.
AB  - Frequency domain photon migration (FDPM) measurements were conducted to assess
      particle interactions of concentrated, monodisperse, polystyrene samples obtained
      directly from industry by using multiple scattering light. The angle-integrated
      static structure factor, S(q), and static structure factor at small wave vector
      q, S(0), were obtained from FDPM measurements at high volume fractions ranging
      from 0.05 to 0.3, and were compared with those obtained from the monodisperse
      hard sphere Percus-Yevick (HSPY) model. Effects of different colloid sizes on
      structure factor evaluated at two different wavelengths were also investigated.
      Results show that the monodisperse HSPY model is suitable for accounting for
      particle interactions and local microstructures in these colloidal suspensions.
      Upon using the HSPY model, particle sizes of polystyrene suspensions were
      recovered from FDPM measurements at high volume fractions (up to 0.3), which
      agree well with the DLS measurement of diluted sample ( approximately 0.001). The
      study of polydispersity effect shows that the FDPM method can be successfully
      used for recovering the mean particle size of polydisperse colloidal suspension
      with low polydispersity (<16%) under the assumption of monodisperse hard sphere
      systems.

PMID- 16290362
TI  - Preparation of monodisperse, fluorescent PMMA-latex colloids by dispersion
      polymerization.
AB  - We report a single step procedure to prepare monodisperse colloidal
      poly(methyl)methacrylate (PMMA) particles where fluorescent dyes are incorporated
      into the polymer network. The particles are sterically stabilized against
      flocculation by poly(12-hydroxystearic acid). The fluorescent dyes are RITC
      (rhodamine isothiocyanate)-aminostyrene (RAS) and 4-methylaminoethylmethacrylate
      7-nitrobenzo-2-oxa-1,3-diazol (NBD-MAEM), which are prepared from (commercially
      available) RITC and 4-chloro-7-nitrobenzo-2-oxa-1,3-diazol (NBD-Cl),
      respectively, as starting materials. The particles can be grown larger with
      nonfluorescent PMMA. Examples of the usefulness of these model particles in
      colloid science are given.

PMID- 16290363
TI  - General solution for Poisson-Boltzmann equation in semiinfinite planar symmetry.
AB  - A unique, simple, and general analytical solution for the nonlinear Poisson
      Boltzmann equation in semiinfinite planar symmetry with any unmixed electrolyte
      is reported. This is an exact solution for symmetrical and z-2z/2z-z asymmetrical
      electrolytes and an approximate solution for other asymmetrical electrolytes (z
      3z/3z-z or 2z-3z/3z-2z). To evaluate the accuracy of the approximate solution,
      the solution was compared with the numerical results obtained from the Galerkin
      weighted residual finite element method. The error of the approximate solution
      for asymmetrical z-3z/3z-z or 2z-3z/3z-2z electrolytes is not more than 1%. This
      new solution unifies all the cases in semiinfinite planar symmetry with any
      unmixed electrolyte into one expression without increasing the mathematical
      complexity. The general solution can serve as a functional approximation for
      potential distribution of two interacting electric double layers when calculating
      electrostatic interaction energy if the superposition approximation is used.

PMID- 16290364
TI  - A simple algorithm for calculating electrical double layer interactions in
      asymmetric electrolytes-Poisson-Boltzmann theory.
AB  - A simple, general, and numerically robust algorithm is presented for calculating
      the disjoining pressure and interaction free energy per unit area between two
      identically charged flat plates due to electrical double layer interactions
      according to the nonlinear Poisson-Boltzmann theory. The result is applicable to
      electrolytes with any number of ionic species having any combination of valencies
      as well as to constant potential, constant charge, or charge regulation boundary
      conditions on the plates. The algorithm is very simple to implement on commonly
      available numerical software environments and is therefore particularly suitable
      for use in data analysis.

PMID- 16290365
TI  - Immobilizing shortened single-walled carbon nanotubes (SWNTs) on gold using a
      surface condensation method.
AB  - We propose a surface condensation method for assembling single-walled carbon
      nanotubes (SWNTs) on gold. The as-prepared long and randomly tangled SWNTs were
      cut into short pipes by chemical oxidation, allowing the nanotubes to be
      terminated by carboxyl functionalities. A surface condensation reaction was then
      performed by immersing an amino self-assembled monolayer (SAM)-modified gold
      substrate into the dimethylformamide suspension of carboxylic nanotubes with the
      aid of dicyclohexylcarbodiimide condensation agent. Raman spectroscopy and atomic
      force microscopy (AFM) results show that a highly aligned assembly of SWNTs has
      been formed on gold, with the nanotubes standing on the surface stable enough for
      a long ultrasonication. In combination with the microcontact printing (muCP)
      technique, we have fabricated patterned nanotube assemblies using this surface
      condensation method. Moreover, we found that the "giant" carbon nanotubes tend to
      form bundles on an amino-terminating surface, likely following a nucleation
      growth model.

PMID- 16290366
TI  - Effect of proton concentration on membrane potential across a weak amphoteric
      polymer membrane.
AB  - An amphoteric membrane consists of both positively and negatively fixed charge
      groups chemically bound to the polymer chains. If the external solution is
      changed from alkali to acid, it is possible to obtain an experimental result in
      which the membrane potential changes from positive to negative through the
      isoelectric point. It was characterized by examining the relationship between
      membrane potential and proton concentration (pH) obtained from both experimental
      and theoretical considerations. The Nernst-Planck flux equation and the Donnan
      equilibrium theory were also solved for a four-component system combined with the
      dissociation constant, in order to discuss the pH dependence of membrane
      potential in a weak amphoteric membrane by comparing the experimental results
      with the calculated results. It was proven that the calculated results
      substantially deviated from the theoretical results despite a similar tendency.
      Such a deviation was caused by the fact that the original theory disregarded the
      activity coefficient and the ionic mobility, which were dependent on the fixed
      charge concentration in a membrane. The original theoretical model was modified
      by adding the effect of a fixed charge group to the activity coefficient and
      ionic mobility. The calculated results using the modified model explained well
      the experimental results if the parameter called charge effectiveness, phi, was
      introduced into the equations. Introduction of phi into the prediction of
      membrane potential was already done by Kobatake et al. in a system of a strong
      polyelectrolyte monopolar membrane/salt aqueous solution. In this study, it was
      proved that phi can also be introduced into a weak amphoteric polymer
      membrane/salt aqueous solution system. Finally it was also concluded that the
      Donnan equilibrium and the Nernst-Planck flux equation were still applicable for
      examining the transport phenomena for the system of a weak amphoteric charged
      membrane and electrolyte solutions at various pH.

PMID- 16290367
TI  - Analysis and characterization of relative permeability and capillary pressure for
      free surface flow of a viscous fluid across an array of aligned cylindrical
      fibers.
AB  - In LCM processes of fiber-reinforced composite manufacturing, resin is injected
      into a closed mold with a preplaced stationary fiber preform. If these preforms
      are created from fiber tows, resin progression at the microlevel during
      infiltration is often non-uniform. Consequently, macroscopic description of the
      filling phase requires a theory of flow through unsaturated porous media in which
      the transition (partly saturated) region must be taken into account. Unsaturated
      flows must consider surface tension effects; therefore, capillary pressure and
      relative permeability must be included in governing equations. This paper
      presents a methodology to determine relative permeability and macroscopic
      capillary pressure for simple flows. The results lead to important conclusions
      and the methodology can be generalized to other flow fields.

PMID- 16290369
TI  - Quantitative analyses of shape-selective intercalation of isomeric mixtures of
      muconates into [LiAl2(OH)6]Cl.yH2O layered double hydroxide.
AB  - Quantitative investigation of the shape selectivity for the competitive
      intercalation reaction of isomeric mixtures in the interlayer of LDH was achieved
      by analyzing the solid phases synthesized by the reaction of
      [LiAl(2)(OH)(6)]Cl.yH(2)O with various compositional mixtures of (E,E)- and (Z,Z)
      muconates. The apparent partition constant K' for the anion-exchange reaction
      between (E,E)- and (Z,Z)-muconates was quite dependent on the mole fraction of
      muconates in solution. The only single phase saturated with
      [LiAl(2)(OH)(6)](2)[(E,E)-C(6)H(4)O(4)].zH(2)O could be obtained in the range of
      the initial mole fraction of (E,E)-muconate larger than 0.6 in the starting
      solution, while mixed phases intercalated with (E,E)- and (Z,Z)-muconates could
      be obtained at lower mole fractions of (E,E)-muconate. The shape selectivity for
      the competitive reaction of two muconates on the [LiAl(2)(OH)(6)](+) lattice
      could be ascribed to thermodynamic processes, and the conditions under which that
      pure (E,E)-muconate was efficiently separated from isomeric mixtures of two
      muconates were successfully evaluated.

PMID- 16290368
TI  - Tailoring the properties of asymmetric cellulose acetate membranes by gas plasma
      etching.
AB  - Cellulose triacetate (CTA) ultrafilters and cellulose acetate blend (CAB)
      desalination membranes were treated with a radiofrequency gas plasma
      (tetrafluoromethane (CF(4)) or carbon dioxide (CO(2)), 47-49 W, 0.04-0.08 mbar).
      Treatment times were varied between 15 s and 120 min. The plasma-treated top
      layer of the membranes was characterized by scanning electron microscopy, X-ray
      photoelectron spectroscopy, and contact angle measurements to obtain information
      about surface structure, chemistry, and wettability, respectively. The membrane
      properties (e.g., permeability, selectivity, fouling) were studied by waterflux
      measurements, molecular weight cutoff measurements, and fouling experiments with
      bovine serum albumin. CO(2) plasma treatment resulted in gradual etching of the
      membrane's dense top layer. Permeation and selectivity changed significantly for
      treatment times of 0-15 min for CTA and 5-60 min for CAB membranes. Moreover, CTA
      membranes were hydrophilized during CO(2) plasma treatment whereas CF(4) plasma
      treatment led to hydrophobic surfaces due to strong fluorination of the top
      layer. This study shows that gas plasma etching can tailor the properties of
      asymmetric cellulose acetate membranes by simultaneously modifying the chemistry
      and structure of the top layer. The low fouling properties of CTA membranes were
      thereby largely maintained.

PMID- 16290370
TI  - A three-dimensional boundary-integral algorithm for thermocapillary motion of
      deformable drops.
AB  - A three-dimensional boundary-integral algorithm has been developed to handle the
      tangential Marangoni stresses in thermocapillary motion of drops. Depending on
      whether the integration and observation points are on the same or different
      drops, singularity or near-singularity subtraction is used in the inhomogeneous
      term of the boundary-integral formulation. Integration is then performed
      analytically over flat triangles in the subtracted region. Relative trajectories
      for two deformable drops are calculated for different values of the drop size
      ratio, drop-to-medium thermal conductivity ratio, and viscosity ratio and
      compared to those for spherical and slightly deformable drops. Results indicate
      that deformation increases the minimum separation and inhibits coalescence but is
      not important enough for appropriate physical parameters to induce the capture or
      breakup behaviors observed in buoyancy. Interaction times calculated by
      artificially continuing spherical drop trajectories yield results accurate to
      within about 10%.

PMID- 16290371
TI  - Kinetics of solubilization of n-decane and benzene by micellar solutions of
      sodium dodecyl sulfate.
AB  - We observed the diminishing of single microscopic oil drops to study the kinetics
      of solubilization of n-decane and benzene by micellar solutions of sodium dodecyl
      sulfate (SDS). Each drop is located in a horizontal glass capillary of inner
      diameter 0.06 cm filled with a thermostated surfactant solution; the small
      vertical dimension of the cell prevents the appearance of uncontrollable thermal
      convections. The experiments show that the radius of an n-decane drop decreases
      linearly with time, whereas for benzene this dependence is nonlinear. To
      interpret the data, a kinetic model of solubilization is developed. It accounts
      for the diffusion and capturing of dissolved oil molecules by the surfactant
      micelles, as well as for the finite rate of oil dissolution at the oil-water
      interface. By processing the data, we determined the rate constant of
      solubilization for a given oil and surfactant. It turns out that the elementary
      act of catching a dissolved oil molecule by a surfactant micelle occurs under a
      barrier (rather than diffusion) control. The effective rate of solubilization is
      greater for the oil, which exhibits a higher equilibrium solubility in pure water
      (benzene), despite the lower value of the solubilization rate constant for this
      oil.

PMID- 16290372
TI  - Interlaminar and ductile characteristics of carbon fibers-reinforced plastics
      produced by nanoscaled electroless nickel plating on carbon fiber surfaces.
AB  - In this work, a new method based on nanoscaled Ni-P alloy coating on carbon fiber
      surfaces is proposed for the improvement of interfacial properties between fibers
      and epoxy matrix in a composite system. Fiber surfaces and the mechanical
      interfacial properties of composites were characterized by atomic absorption
      spectrophotometer (AAS), scanning electron microscopy (SEM), X-ray photoelectron
      spectrometry (XPS), interlaminar shear strength (ILSS), and impact strength.
      Experimental results showed that the O(1s)/C(1s) ratio or Ni and P amounts had
      been increased as the electroless nickel plating proceeded; the ILSS had also
      been slightly improved. The impact properties were significantly improved in the
      presence of Ni-P alloy on carbon fiber surfaces, increasing the ductility of the
      composites. This was probably due to the effect of substituted Ni-P alloy,
      leading to an increase of the resistance to the deformation and the crack
      initiation of the epoxy system.

PMID- 16290373
TI  - Dynamic and static light scattering study on the sol-gel transition of resorcinol
      formaldehyde aqueous solution.
AB  - Structure formation during the sol-gel transition of resorcinol-formaldehyde (RF)
      solutions was traced by dynamic light scattering (DLS) and static light
      scattering (SLS) techniques. The decay time spectra obtained by DLS revealed that
      both the growth rates of colloidal particles formed during the early stage of the
      sol-gel transition and the time required for the colloidal particles to form a
      firm network structure could be related to the ratio of catalyst to water (C/W)
      of the starting RF solution. SLS results indicated that the molecular weight of
      colloidal particles increased with the progress of the sol-gel transition, the
      rate of which was also affected by the value of C/W. The mesoporosity of RF
      aerogels, which were prepared by drying RF hydrogels with supercritical carbon
      dioxide, was confirmed to depend on the size of colloidal particles estimated
      from the decay time spectrum collected at the last stage of the sol-gel
      transition.

PMID- 16290374
TI  - Molecular weight effect on latex film formation induced by solvent vapor: an
      optical transmission study.
AB  - Two different sets of powder latex film were prepared from high- and low
      molecular-weight (HM and LM) poly(methyl methacrylate) (PMMA). The optical
      transmission method was used to the study film formation induced by organic
      vapor. Various HM and LM films with the same latex content were prepared
      separately from the PMMA particles and exposed to vapor of a chloroform-heptane
      mixture in various volume percents of chloroform. Transmitted light intensities,
      I(tr), from these films increased in time under vapor exposure, which was
      attributed to the increase in "crossing density" at the junction surface. The
      Prager-Tirrell model was employed to obtain the back-and-forth frequency, nu, of
      the reptating polymer chain during film formation induced by solvent vapor. nu
      values were obtained and found to be strongly correlated with the percent of
      chloroform in the solvent mixture and the molecular weight of the polymer chain.
      It is observed that high-molecular-weight chains reptate much more slowerly than
      low-molecular-weight chains.

PMID- 16290375
TI  - A study of cyclohexane diffusion in hybrid (organic/inorganic) gels monitored by
      an oscillating balance reactor.
AB  - Hybrid (organic/inorganic) gels are studied in terms of cyclohexane diffusion
      transients with an oscillating balance reactor (OBR) which, unlike conventional
      microbalances, has the well-defined gas flow profile characteristics of packed
      beds (PB's). The OBR-based flow-through adsorption system, when properly
      designed, has very good time resolution and is particularly useful in modeling
      adsorption processes under more realistic PB geometries. With the test sample
      adopted in this study, the "semirigid" nature of hybrid gels becomes apparent
      when simple relaxation models are chosen to fit experimental data.

PMID- 16290376
TI  - Direct surface force measurement in water using a nanosize colloidal probe
      technique.
AB  - The direct force measurement between colloidal surfaces has been an essential
      topic in both theories and applications of surface chemistry. As particle size is
      decreased from micron size down to true nano size (<10 nm), surface forces are
      increasingly important. Nanoparticles at close proximity or high solids loading
      are expected to show a different behavior than what can be estimated from
      continuum and mean field theories. The current tools for directly measuring
      interaction forces such as a surface force apparatus or atomic force microscopy
      (AFM) are limited to particles much larger than nanosize. Here a modified
      colloidal probe technique is suggested using a multiwalled carbon nanotube (MWNT)
      to overcome this problem. Determination of zero separation in AFM is critical to
      extract a reliable force-separation curve when MWNT is used as a probe. Hence, a
      systematic approach to the data collection for a nanosize colloidal probe is
      proposed and a sample of a direct surface force measurement curve obtained with
      the MWNT probe is presented.

PMID- 16290378
TI  - On the adsorption/oxidation of hydrogen sulfide on activated carbons at ambient
      temperatures.
AB  - Activated carbons of various origins (bituminous coal, wood, coconut shells, and
      peat) were studied as adsorbents of hydrogen sulfide. Before the experiments the
      surface of the adsorbents was characterized by using the sorption of nitrogen,
      Boehm and potentiometric titrations, thermal analysis, and FTIR. The adsorbents
      were chosen to differ in their surface areas, pore volumes, and surface
      acidities. To broaden the spectrum of surface acidity, carbons were oxidized by
      using nitric acid and ammonium persulfate. After hydrogen sulfide adsorption the
      species present on the surface were analyzed using thermal analysis, ion
      chromatography, and elemental analysis. The H(2)S breakthrough capacity tests
      showed that the performances of different carbons differ significantly. For a
      good performance of carbons as hydrogen sulfide adsorbents a proper combination
      of surface chemistry of carbon and porosity is needed. It was demonstrated that a
      more acidic environment promotes the formation of sulfur oxides and sulfuric acid
      despite yielding small H(2)S removal capacities. On the other hand, a basic
      environment favors the formation of elemental sulfur (sulfur radicals) and yields
      high capacities. The presence of a sufficient amount of water preadsorbed on the
      carbon surface to facilitate dissociation also plays an important role in the
      process of H(2)S adsorption/oxidation. The results showed that there is a
      critical value in carbon surface acidity, which when exceeded results in a
      negligible hydrogen sulfide breakthrough capacity. This is consistent with the
      mechanism of H(2)S adsorption on unmodified carbons, where the rate-limiting step
      is the reaction of adsorbed hydrogen sulfide ion with dissociatively adsorbed
      oxygen. When the acidity is expressed as pH, its value should be higher than 5 to
      ensure the effective removal of hydrogen sulfide from the gas phase. Study of
      carbon regeneration using water washing and heat treatment showed that the
      adsorbents can be regenerated to about 40% of their initial capacity.

PMID- 16290379
TI  - A silicate gel for promoting deposition of lipid bilayers.
AB  - A simple method for modifying a polymer surface to induce lipid bilayer formation
      by vesicle fusion is described. A silicate gel was prepared by condensation of
      tetraethyl orthosilicate (TEOS) in the presence of acid. When applied to a
      poly(methylmethacrylate) substrate, either a rough or a smooth layer could be
      produced, depending on the method used for the application. The smooth surface
      induced formation of a supported lipid bilayer by fusion of lipid vesicles; the
      rough silicate surface induced adsorption of a vesicle layer. A high-frequency
      acoustic waveguide device was used to follow the initial adsorption of vesicles,
      the transition from a vesicle layer to a bilayer, and the formation of a complete
      bilayer; the time required to form a bilayer was determined as a function of
      lipid concentration in suspension. The presence of a bilayer on the smooth
      silicate surface was confirmed by fluorescence recovery after photobleaching. An
      additional procedure is described to modify a gold surface to induce bilayer
      formation.

PMID- 16290380
TI  - Dependence of the adsorption of polymer mixtures from solution on the amount of
      an adsorbent.
AB  - Simultaneous competitive adsorption from solutions of mixtures of poly(butyl
      methacrylate) and polystyrene and adsorption of each component from binary
      solutions have been studied for three ratios of the adsorbent mass to the
      solution volume, A/V. It was found that adsorption from both binary and ternary
      solutions strongly depends on the amount of an adsorbent, adsorption of
      poly(butyl methacrylate) being preferential. The characteristic adsorption
      isotherms of both polymers were constructed under conditions of equal equilibrium
      concentration of each component to estimate the parameters of preferential
      adsorption and their dependence on the A/V ratio. It was found that the A/V
      effect plays an important role in adsorption from polymer mixtures and determines
      the peculiarities of adsorption from polymer mixtures as well as from solution of
      single polymers. Changing the A/V ratio may be one way to regulate the
      composition of an adsorption layer consisting of two chemically different
      polymers. The reasons for the A/V effect are considered in the framework of the
      concept of the plurality of adsorption equilibria between two chemically
      different components and between fractions of different molecular mass of each
      component having various absorbability.

PMID- 16290381
TI  - Adsorption properties of iodine-doped activated carbon fiber.
AB  - Iodine-doped activated carbon fibers (ACFs) were prepared by the iodine immersion
      method on pitch-based ACF. Then iodine-doped ACFs were heated in argon at 523 K
      for 4 h and at 673 K for 2 h. The iodine structure of the resultant iodine-doped
      ACFs was examined using X-ray photoelectron spectroscopy. The micropore
      structures were determined by N(2) adsorption at 77 K. The surface area and
      micropore volume of iodine-doped ACFs are less than those of pristine ACFs.
      However, the pore width does not change with the iodine doping. The effects of
      iodine doping on adsorption properties of ACFs for H(2)O and NO at 303 K were
      examined. The iodine doping affected remarkably the adsorptivities of ACFs for
      H(2)O and NO. In particular, iodine-doped ACFs treated at 673 K show enhanced
      adsorptivities for H(2)O and NO. This result suggests that iodine molecules doped
      on the micropores should be charged by heat treatment at 673 K.

PMID- 16290383
TI  - Preparation and properties of starch-based colloidal microgels.
AB  - Novel starch microgels were prepared by emulsion cross-linking and characterized
      with respect to shape, volume, and mass density. Starch microgels appear to be
      negatively charged ( approximately -50 mV), with a particle size varying as a
      function of the type of cross-linker (ca. 0.25-10 microm). Environmental scanning
      electron microscopy observations show a dependence of the particle swelling on
      the cross-linking density. Viscosimetry reveals that starch microgels behave as
      charged polymers, where the reduced viscosity increases with dilution (anomalous
      viscosity behavior) for sufficiently low kappaalpha (ca. kappaalpha <3), the
      ratio of the particle radius (a), and the Debye length (kappa(-1)). Analogous
      results are obtained for reference-charged rigid silica spheres, which approach
      the hard sphere limit for increasing ionic strengths. The shape of the microgels
      appears to play a minor role in the anomalous viscosity behavior, which is more
      likely dominated by electrostatic effects.

PMID- 16290382
TI  - Protein adsorption on supported phospholipid bilayers.
AB  - Quartz crystal microbalance with dissipation (QCM-D) measurements were used to
      investigate the adsorption of human fibrinogen, human serum albumin, bovine
      hemoglobin, horse heart cytochrome c, human immunoglobulin (hIgG), and 10% fetal
      bovine serum on supported bilayers of egg-phosphatidylcholine (eggPC) lipids. For
      comparison the adsorption of fibrinogen and hIgG to eggPC bilayers was also
      studied with surface plasmon resonance (SPR). The supported bilayers were formed
      in situ by vesicle adhesion and spontaneous fusion onto a SiO(2) surface. The
      supported lipid bilayer is highly protein resistant: The irreversible adsorption
      measured with the QCM-D technique was below the detection level, while reversible
      protein adsorption was detected for all the proteins in the range 0.3-4% of the
      saturation coverage on a hydrophobic thiol monolayer on gold. The adsorbed
      amounts were slightly higher for the SPR measurements. Possible mechanisms for
      the protein resistance of eggPC bilayers are briefly discussed.

PMID- 16290384
TI  - Interfacial interactions of hydrophobic peptides with lipid bilayers.
AB  - Four hydrophobic laminin-related peptides and their corresponding parent peptides
      were synthesized to use them to target liposomes to tumoral cells. The peptide
      sequence was YIGSR((NH(2))), and hydrophobic residues linked to the alpha-amino
      terminal end were decanoyl, myristoyl, stearoyl, and cholesteryl-succinoyl.
      Before use in biological systems, a physicochemical study was carried out in
      order to determine their interaction with DPPC bilayers that could compromise
      both the toxicity and the stability of liposomal preparations. The experiments
      were based on DSC, fluorescence polarization, outer-membrane destabilization, and
      vesicle leakage. These peptides showed in general a low interaction with the
      vesicles, promoting in all cases the rigidification of bilayers. This lack of
      strong disturbances in the ordered state of phospholipid molecules seems more
      likely due to the similarity of peptide acyl chains with those of lipids than to
      the absence of interactions. The bulkiness of cholesteryl derivative as well as
      its tendency toward aggregation resulted in weak interaction levels except in
      thermograms. The binding of peptides to the surface of liposomes loaded with
      doxorubicin resulted in preparations with good entrapment yields and small size,
      required for long circulating vesicles (especially for the myristoyl derivative).
      The alternative method based on the reaction of parent peptide to the surface of
      liposomes through an amide linkage was slightly more efficient when the peptide
      was linked to the carboxy-terminal end of the DSPE-PEG-COOH-containing liposomes.
      Nevertheless, the final decision must be made with the simplicity of the
      procedure and reduction in losses during all the steps of the processes taken
      into consideration.

PMID- 16290386
TI  - Sonochemical synthesis of cerium oxide nanoparticles-effect of additives and
      quantum size effect.
AB  - Cerium oxide (CeO(2)) nanoparticles were prepared sonochemically, by using cerium
      nitrate and azodicarbonamide as starting materials, and ethylenediamine or
      tetraalkylammonium hydroxide as additives. The additives have a strong effect on
      the particle size and particle size distribution. CeO(2) nanoparticles with small
      particle size and narrow particle size distribution are obtained with the
      addition of additives; while highly agglomerated CeO(2) nanoparticles are
      obtained in the absence of additives. Monodispersed CeO(2) nanoparticles with a
      mean particle size of ca. 3.3 nm are obtained when tetramethylammonium hydroxide
      (TMAOH) is used as the additive and the molar ratio of cerium
      nitrate/azodicarbonamine/TMAOH is 1/1/1. Blue shifts of the absorption peak and
      the absorption edges of the products are observed in the UV-Vis absorption
      spectra as a result of the quantum size effect. The samples have been
      characterized using powder XRD, TEM, DLS, and absorption spectra.

PMID- 16290385
TI  - Effect of electrostatic interaction on the adsorption of globular proteins on
      octacalcium phosphate crystal film.
AB  - The electrostatic effect on the adsorption of globular proteins, such as bovine
      serum albumin (BSA), hen egg white lysozyme (LZM), and beta-lactoglobulin (beta
      Lg), on octacalcium phosphate (OCP)-like crystal thin films was investigated. A
      poorly crystalline thin film was synthesized on a tissue culture polystyrene
      (TCP) surface and used as a model surface in this study. The solution pH clearly
      affected the electrostatic properties of both proteins and surface. The adsorbed
      amounts obtained at quasi-steady state were readily related to the solution pH
      for each protein. The adsorption rate is fast during the initial period and
      levels off gradually. The maximum adsorbed mass occurred at pH 7 for BSA and at
      pH 9 for LZM. beta-Lg adsorbed similar amounts at pHs lower than 9, but the
      adsorbed mass decreased at pHs higher than 9 where electrostatic repulsion
      exists. The pH values where the maximum adsorbed mass occurred may be considered
      as the conditions where electrostatic attraction is most favorable. The adsorbed
      mass of beta-Lg was the greatest among the proteins of interest while BSA
      adsorbed the least despite its greater molecular mass. LZM falls into the
      intermediate region. According to these observations, BSA has undergone
      conformational changes that prevent further adsorption to a greater extent than
      the others. A simple relationship between the adsorption rate and the
      electrostatic properties was not established. However, the order of magnitude of
      the adsorption rate at the initial period tends to be the same as that of maximum
      adsorbed mass for each protein.

PMID- 16290387
TI  - Change in particle size distribution of fractal agglomerates during Brownian
      coagulation in the free-molecule regime.
AB  - Time evolution of particle size distribution of fractal agglomerates undergoing
      Brownian coagulation in the free-molecule regime was investigated. A simple
      analytical solution for the size distribution change was obtained by using the
      assumption that the size distribution during the coagulation process can be
      represented by a time-dependent log-normal function. The derived solution
      consists of three parameters of the log-normal distribution function. This study
      is believed to provide the first analytical solution for all the parameters of
      the log-normal distribution of fractal agglomerates undergoing coagulation in the
      free-molecule regime. To validate the derived solution, numerical computations
      were performed. The results were compared with the analytical solution and good
      agreement was obtained.

PMID- 16290388
TI  - Silver-palladium nanodispersions in silicate matrices: highly uniform, stable,
      bimetallic structures.
AB  - Ag-Pd nanobimetallic colloidal particles are prepared in a single step by a
      chemical reduction method. Organically modified aminosilicate is used as a
      supporting matrix as well as a stabilizing agent, to obtain very uniform, well
      distributed bimetallic particles. These nanoparticles are found to be stable for
      several months in both the solid and the liquid phases. The structure of the
      bimetallic particles has been followed by X-ray photoelectron spectroscopy and
      ultraviolet-visible spectroscopy. The distribution and the particle size are
      determined by transmission electron microscope and X-ray diffraction studies.
      Polymerization and condensation of the support silicate material have been
      confirmed by Fourier transform infrared spectroscopy.

PMID- 16290389
TI  - The liquid flow force on a particle in the bubble-particle interaction in
      flotation.
AB  - In this paper the problem of calculating the liquid flow force on a particle in
      interaction with an air bubble with a mobile surface in flotation as a function
      of the separation distance was solved. The force equation was obtained by first
      deriving the disturbed flow confined between the surfaces. The model for the
      force includes the separation distance between the bubble and the particle, the
      particle size, the bubble's Reynolds number, the bubble rise velocity, and the
      polar position of the particle on the bubble surface. The proposed equations
      provide an exact solution to the situation where the particle and the bubble are
      very close together. The attractive flow force and the surface forces are of
      similar orders of magnitude. Consequently, the models presented in this paper
      should provide a better estimate for calculating the forces on particles
      interacting with air bubbles in mineral flotation and other separation operations
      involving colloidal interactions.

PMID- 16290390
TI  - The influence of cold treatment on properties of temperature-sensitive poly(N
      isopropylacrylamide) hydrogels.
AB  - Poly(N-isopropylacrylamide) (PNIPAAm) hydrogel exhibits a response to external
      temperature variation and shrinks in volume abruptly as the temperature is
      increased above its lower critical solution temperature. It has great potential
      applications in biomedical fields. A rapid response rate is essential, especially
      when this material is designed as an on-off switch for targeted drug delivery.
      However, due to the appearance of a thick, dense skin layer on the hydrogel
      surface during the shrinking process, the deswelling rate of conventional PNIPAAm
      gels is low. In this article, a novel method is proposed to modify the surface
      morphology of PNIPAAm gel, in which the swollen gels are frozen at low
      temperature (-20 degrees C). The scanning electron micrographs revealed that a
      fishnet-like skin layer appeared on the surfaces of the cold-treated gels.
      Dramatically rapid deswelling was achieved with the cold-treated gels since the
      fishnet-like structure with numerous small pores prevented the formation of a
      dense, thick skin layer during the deswelling process, which commonly occurs in
      normal PNIPAAm hydrogels. Prolonging the cold treatment from 1 day to 10 days
      resulted in a slightly higher deswelling rate. Rearrangement of the hydrogel
      matrix structure during the freezing process might contribute to the formation of
      the fishnet-like skin layer. The water uptake of the hydrogels increased nearly
      in proportion to the square root of time, indicating that the reswelling rate of
      hydrogels was controlled predominantly by water diffusion into the network.
      However, there were no significant differences in the equilibrated swelling ratio
      and reswelling kinetics at room temperature (22 degrees C) between normal gels
      and cold-treated gels, which implied that cold treatment did not change bulk
      porosity and gel tortuosity much.

PMID- 16290391
TI  - A 2D electrohydrodynamic model for electrorotation of fluid drops.
AB  - A theoretical analysis of spontaneous electrorotation of deformable fluid drops
      in a DC electric field is presented with a 2D electrohydrodynamic model. The
      fluids in the system are assumed to be leaky dielectric and Newtonian. If the
      rotating flow is dominant over the cellular convection type of
      electrohydrodynamic flow, closed-form solutions for drops of small deformations
      can be obtained. Because the governing equations are in general nonlinear even
      when drop deformations are ignored, the general solution for even undeformed drop
      takes a form of infinite series and can only be evaluated by numerical means.
      Both closed-form solutions for special cases and numerical solutions for more
      general cases are obtained here to describe steady-state field variables and
      first-order drop deformations. In a DC electric field of strength beyond the
      threshold value, spontaneous electrorotation of a drop is shown to occur when
      charge relaxation in the surrounding fluid is faster than the fluid inside the
      drop. With increasing the strength of the applied electric field from the
      threshold for onset of electrorotation, the axis of drop contraction deviates
      from from that of the applied electric field in the direction of the rotating
      flow with an angle increasing with the field strength.

PMID- 16290392
TI  - Luminescent properties of tris(2,2'-bipyridine)ruthenium(II) in sol-gel-processed
      dip-coated thin films.
AB  - The luminescence decay and spectral behavior of ruthenium(II)-tris-1,2-bipyridine
      dichloride dissolved in different organically modified silicate gel matrixes were
      investigated. Dip-coated thin films were synthesized from tetraethoxysilane
      (TEOS), methyltriethoxysilane (MTEOS), ethyltriethoxysilane (ETEOS), and methyl-
      trimethoxysilane (MTMOS). A blue shift in the ruthenium complex emission spectrum
      with respect to the aqueous solution was observed for all the films on the sol to
      gel conversion. This spectral shift was slightly dependent on the precursor used
      to obtain the films and independent of the reaction pH to prepare the "sol". In
      the data treatment of the time-resolved luminescence measurements, it was assumed
      that the distribution of the luminophore in the films was nonhomogeneous. The
      analysis of the luminescence decay profiles was based on a multisite model. All
      decay curves are best described by a double-exponential model. The parameters of
      the decay components depended principally on the thermal treatment used in the
      processing of the films. The lifetimes decreased and the emission espectra showed
      a red shift with the increase in the drying temperature. A luminescence quenching
      of the ruthenium complex in the films by dissolved oxygen in aqueous solution was
      also observed. The quenching rate constant obtained from the preexponential
      amplitude-weighted mean lifetimes (tau(M)) was in the order of 10(9) M(-1) s(-1).
      When a phenolic derivative was used as quencher the process rate was greatly
      reduced compared to the quenching in water. It would seem that the metallic
      complex sequestered within the film is placed either into a higher microviscosity
      microenvironment or in a location which the phenolic quencher cannot access. In
      both cases, the quenching plot based on tau(o)(M)/tau(M) could be fitted
      satisfactorily by a sum of two terms of Stern-Volmer. This fact is indicative of
      the matrix microheterogeneity for the films and is fully consistent with the
      biexponential nature of the luminescence intensity decay profiles.

PMID- 16290393
TI  - Influence of drying procedure on the mesoporosity and surface fractal dimensions
      of silica xerogels prepared with different agitation methods.
AB  - Silica xerogels were prepared by thermal drying wet gels in an electric oven (70
      degrees C) after certain duration of ambient drying, and the relevant effect is
      investigated on the mesopore structures and surface fractal dimensions of the
      resultant xerogels. The silica gels were derived from a hydrochloric acid
      catalyzed TEOS (tetraethylorthaosilicate) system, and both magnetic stirring and
      ultrasonic vibration were adopted during sol preparation. The percentage
      mesoporosity and surface fractal dimensions are evaluated using image analysis
      methods, based on FE-SEM (field emission gun-scanning electron microscopy)
      images. The results show that the mesoporosity of the resultant xerogels
      decreases with the duration of ambient drying for samples prepared using magnetic
      stirring and low-intensity ultrasonic vibration, while samples subjected to high
      intensity ultrasound show a somewhat reverse trend. Samples prepared with
      magnetic stirring have almost constant surface fractal dimensions (nearly 3),
      irrespective of the ambient drying before thermal drying. The surface fractal
      dimensions of samples prepared using ultrasound increase with the duration of
      ambient drying.

PMID- 16290394
TI  - Ink-bottle effect in mercury intrusion porosimetry of cement-based materials.
AB  - Mercury intrusion porosimetry (MIP) is a widely used method for studying porous
      materials, in particular, cement-based materials. The usual interpretation of
      such measurements is based on certain assumptions. One of these is that each pore
      is connected to the sample surface directly or through larger pores. Pores not
      meeting this assumption are called ink-bottle pores. The effect that sample size
      has on the MIP characteristics of concrete samples, like the ink-bottle effect
      and hysteresis, was studied by measuring additional extrusion and intrusion
      cycles. In order to characterize the extrusion and ink-bottle behavior, the
      amount of entrapped mercury chi(p) was estimated. Superimposition of extrusion
      and second intrusion curves is achieved if the contact angle theta is adjusted
      from theta(i), the intrusion contact angle, to theta(e), the extrusion contact
      angle. The threshold radius is often assumed to be a dominant pore radius, yet in
      this study the entrapped mercury content shows no evidence for the presence of a
      dominant pore radius. Even if characteristic properties of cement-based materials
      can be estimated with MIP, comparison of results is rendered difficult by the
      significant effects of sample preparation techniques and sample size and the ink
      bottle effect due to randomly present air bubbles.

PMID- 16290395
TI  - A comparison of electrochemical and electrokinetic parameters determined for
      cellophane membranes in contact with NaCl and NaNO3 solutions.
AB  - Electrochemical and electrokinetic characterizations of cellophane membrane
      samples have been carried out by measuring membrane potential, salt diffusion,
      and tangential streaming potential, which allow the determination of different
      characteristic membrane parameters. Experiments were made with the membrane
      samples in contact with NaCl and NaNO(3) solutions at different concentrations
      and under different external conditions (concentration gradients), in order to
      obtain differences in transport and membrane characteristic parameters, depending
      on the electrolyte considered. Salt permeability across the membrane, which was
      obtained from diffusion measurements, is about twice as high for NaCl solutions
      as for NaNO(3) solutions, which is attributed to the different sizes of the
      electrolytes. Membrane potential measurements keeping the concentration ratio
      constant (C(1)/C(2)=2) were used to determine both the effective fixed charge
      concentration in the membrane, X(f), and the average value of transport numbers,
      t(i); taking into account these values, concentration dependence of membrane
      potential under a different external condition (C(1)=cte=0.01 M, 5 x 10(-3)< or
      =C(M)< or =5 x 10(-2)) was predicted. Results show that cellophane membrane
      behaves as a weak cation-exchange membrane and its permselectivity to cations is
      practically independent of the electrolyte considered. From electrokinetic
      results, assuming a Langmuir-type adsorption of anions on the cellophane surface,
      the number of accessible sites per surface unit was obtained, which is higher for
      Cl(-) than for NO(3)(-), in agreement with the small radii of chlorine ions;
      however, no significant differences in the specific adsorption free energy were
      found (DeltaG(Nacl)=-22.0 x 10(3) J/mol) and (DeltaG(NaNO(3))=-23.2 x 10(3)
      J/mol).

PMID- 16290396
TI  - Comparison of polysulfone and ceramic membranes for the separation of phenol in
      micellar-enhanced ultrafiltration.
AB  - Micellar-enhanced ultrafiltration (MEUF) of phenol and a cationic surfactant,
      cetylpyridinium chloride (CPC), is studied using two polysulfone membranes of 5-
      and 50-kDa molecular weight cutoff (MWCO) and two ceramic membranes of 15- and 50
      kDa MWCO. Filtrations are run under laminar cross-flow and steady-state
      conditions. The effect of operation variables (pressure and retentate flux) and
      membrane properties (nature and MWCO) on permeate flux, surfactant, and phenol
      rejections is analyzed. The permeate flux depends, among other variables, on the
      fouling favored by membrane-micelle interactions, which are strongest in the 50
      kDa MWCO ceramic membrane. On the other hand, surfactant rejection is mainly
      determined by the pore size and influenced by the pressure for both 50-kDa MWCO
      membranes. An equilibrium distribution constant, K(s), of phenol between
      surfactant micelles and water is calculated. Its value is not significantly
      affected by operation conditions and membrane type. K(s) is also approximately
      20% lower than the value determined in a previous work with batch dead-end
      ultrafiltration.

PMID- 16290397
TI  - Deintercalation of hydrazine-intercalated kaolinite in dry and moist air.
AB  - The deintercalation of hydrazine-intercalated kaolinite has been followed using a
      combination of X-ray diffraction and diffuse reflectance Fourier transform
      infrared spectroscopy. Upon intercalation of the kaolinite with hydrazine, the
      kaolinite layers are expanded to 10.66 A and remain expanded for up to 22 h upon
      exposure to moist air. Only upon deintercalation are the peak at 10.39 A and a
      minor peak at 9.6 A observed. Complete deintercalation takes up to 18 days more.
      Upon intercalation with hydrazine an intense band is observed at 3628 cm(-1) and
      is attributed to the inner-surface hydroxyls hydrogen bonded to the hydrazine,
      which upon deintercalation decreased in intensity. This rate of deintercalation
      is affected by the presence or absence of moist air. Deintercalation in the
      presence of water vapor results in the observation of two additional bands at
      3550 and 3598 cm(-1), which are attributed to the hydroxyl stretching modes of
      adsorbed water during deintercalation. The intensity of NH stretching vibrations
      observed at 3360, 3300, and 3200 cm(-1) also decrease in intensity with
      deintercalation time. Changes in the hydroxyl deformation modes of kaolinite in
      the 915 cm(-1) region and in the HNH deformation modes show strong interactions
      between the kaolinite surface and the inserting hydrazine molecule.

PMID- 16290398
TI  - Alkanediyl-alpha,omega-bis(dimethylalkylammonium bromide) surfactants 9. Effect
      of the spacer carbon number and temperature on the enthalpy of micellization.
AB  - The enthalpies of dilution of micellar solutions of several 12-s-12 dimeric
      surfactants of the alkanediyl-alpha,omega-bis(dodecyldi-methylammonium bromide)
      type, differing by the carbon number s of the alkanediyl spacer, and of
      dodecyltrimethylammonium bromide (DTAB) have been measured calorimetrically, in a
      range of concentrations extending from well below to well above the critical
      micelle concentration (cmc). The results permitted the determination of the
      enthalpy of micellization, DeltaH degrees (M), of the investigated surfactants at
      25 and 35 degrees C. The values of DeltaH degrees (M) were always negative and
      became more negative as the temperature was increased. The plot of -DeltaH
      degrees (M) against s showed a shallow minimum at about s=5 and a large decrease
      of -DeltaH degrees (M) going from 12-2-12 to 12- 4-12. This effect has been
      attributed to the contribution to DeltaH degrees (M) of the hindered rotation of
      the dodecyl chains around the spacer C-C bond for 12-2-12. This hindrance is
      shown to rapidly disappear when s is increased from 2 to above 4. The specific
      heats of micellization, the free energies of micellization, and the entropies of
      micellization (DeltaS degrees (M)) have been calculated using the DeltaH degrees
      (M) values and the reported cmc and micelle ionization degree data for 12-s-12
      surfactants and DTAB. For all surfactants the results show that TDeltaS degrees
      (M)>-DeltaH degrees (M), indicating an entropy-driven micellization.

PMID- 16290399
TI  - Alkanediyl-alpha,omega-bis(dimethylalkylammonium bromide) surfactants 10.
      Behavior in aqueous solution at concentrations below the critical micellization
      concentration: an electrical conductivity study.
AB  - Ion pairing and premicellar association have been often invoked to explain
      results obtained in studies of aqueous solutions of ionic dimeric surfactants
      (gemini surfactants), mainly by means of surface tension and electrical
      conductivity, at concentrations below the critical micellization concentration
      (cmc). The present work was undertaken in an attempt to find out under which
      conditions these effects come into play. For this purpose the electrical
      conductivity of solutions of many dimeric surfactants of the type spacer
      alpha,omega-bis(alkyldimethylammonium bromide) have been measured. The alkyl
      chain contained m=10-18 carbon atoms. The spacer group was either an alkanediyl
      with s carbon atoms (m-s-m surfactants) or a xylylene m-xylyl-m surfactants). The
      results show that ion pairing occurs in solutions of m-s-m dimers with m< or =10,
      mostly as a result of their high cmc values. The results for 12-s-12 dimers with
      s< or =10 and for 12-xylyl-12 showed no evidence of either ion pairing or
      premicellar association. Premicellar association was present for 12-s-12 dimers
      with s> or =12, for m-8-m dimers with m> or =14, and for 16-xylyl-16. It showed
      through a positive curvature of the specific conductivity versus concentration
      plot and the presence of a maximum in the equivalent conductivity vs
      (concentration)(0.5) plot at concentrations below the cmc. The free energy
      associated with the premicellar association of m-8-m dimers has been estimated
      from the available cmc and micelle ionization degree data.

PMID- 16290400
TI  - Interaction between a novel gemini surfactant and cyclodextrin: NMR and surface
      tension studies.
AB  - The interaction between cyclodextrins, hydroxypropyl-beta-cyclodextrin
      (HPbetaCD), and hydroxypropyl-gamma-cyclodextrin (HPgammaCD) and a novel type of
      nonionic surfactant synthesized from a fatty acid has been investigated. The so
      called nonionic heterogemini surfactant (NIHG750) contains two hydrophobic groups
      and two hydrophilic groups, composed of one monomethyl ethylene glycol and one
      secondary OH group, CH(3)(CH(2))(7)-CH[OH]-CH[O(CH(2)CH(2)O)(16)CH(3)]
      (CH(2))(7)CN. Surface tension studies indicate that micelles form in NIHG750
      systems in both the presence and the absence of small quantities (molar ratio
      (HPbetaCD:NIHG750) approximately 2) of cyclodextrin (HPbetaCD or HPgammaCD). This
      gives NIHG surfactants an advantage compared to single-tailed nonionic
      surfactants, which generally lose their ability to micellize at much lower
      additions of cyclodextrins. However, the interaction between HPbetaCD and NIHG750
      results in a disruption of the micellar aggregates at higher levels of
      cyclodextrin. In the dilute systems (C(NIHG750)<0.1% (w/w) approx) prolate-shaped
      mixed aggregates (HPbetaCD and NIHG750) form, with a short and a long axis of the
      order of 8-9 and 17-20 A, respectively. These gradually aggregate into micellar
      like structures at higher concentrations. In the aqueous bulk phase HPbetaCD
      interacts mainly with the hydrophobic part of NIHG750, but both NMR and surface
      tension measurements indicate that an interaction with the hydrophilic part of
      NIHG750, as well, may exist. This interaction results in a better packing of
      NIHG750 at air-water interfaces. However, at elevated temperatures results from
      turbidity measurements indicate that NIHG750 and HPbetaCD interact mainly through
      the hydrophilic part of the surfactant; a decrease in the cloud point temperature
      is observed. The interaction of the larger cavity molecule, HPgammaCD, with
      NIHG750, on the other hand, seems to be relatively weak. The interaction, when
      present, most probably takes place through inclusion of the hydrophilic EO part
      of NIHG750. The results suggest that HPgammaCD in combination with NIHG750 is a
      better solubilizing system than with HPbetaCD.

PMID- 16290401
TI  - Dynamics of capillary imbibition when surfactant, polymer, and hot water are used
      as aqueous phase for oil recovery.
AB  - Capillary imbibition is an oil recovery mechanism in naturally fractured
      reservoirs if rock matrix is water wet and there is enough water in fractures in
      contact with matrix. It, however, may not yield an effective recovery under
      certain circumstances even if these conditions are maintained. Heavy matrix oil,
      high interfacial tension (IFT), oil-wet matrix sample, and limited contact area
      of matrix with water in fractures require additional effort to enhance the oil
      recovery by capillary imbibition. Chemicals and heat can be injected into
      naturally fractured reservoirs to improve the capillary imbibition recovery
      performance. With the involvement of low IFT fluid, heat, and polymer solution in
      the process, capillary imbibition dynamics may change and this entails an
      identification of the dynamics of the process through laboratory experiments
      before injection of these expensive fluids into oil reservoirs. In this study,
      the dynamics of capillary imbibition was studied experimentally. Static
      imbibition experiments were conducted on oil- and water-wet rock samples under
      different boundary conditions and saturated with different types of oil. The
      analyses were conducted using three indicators, namely the capillary imbibition
      rate, ultimate oil recovery, and shape of the recovery profile. Based on these
      indicators, the dynamics of capillary imbibition of different aqueous phases were
      evaluated for different oil types and matrix properties. The conditions that
      cause weak or strong capillary imbibition were identified.

PMID- 16290405
TI  - Zwitterionic latex particles as an effective carrier for DNA.
AB  - The ability of small particles to associate with DNA and to transport it to
      desired targets without being subjected to interferences can make them efficient
      vehicles for gene delivery. Keeping these requirements in mind, zwitterionic
      latex particles with two different functional tethers were chosen for studying
      their interaction with DNA as vehicle complexes. From adsorption and
      electrokinetic studies, it is evident that zwitterionic latex particles can have
      marked association with DNA. Moreover, DNA-latex complexation does not provoke
      undesired aggregation of latex particles. These characteristics are important for
      it to carry the DNA efficiently under changing media conditions.

PMID- 16290402
TI  - Stability of polycarbonate and polystyrene surfaces after hydrophilization with
      high intensity oxygen RF plasma.
AB  - A general drawback observed with plasma treatment is the limited stability of the
      hydrophilic-treated surfaces toward washing, storage, or heating. It has recently
      been found that oxygen, air, or argon radiofrequency plasmas with higher
      intensities than normally used can give hydrophilic surfaces having good wash
      stability. High intensity oxygen plasma treatment of polystyrene and
      polycarbonate surfaces was therefore carried out using two different capacitively
      coupled RF reactors with internal shelf electrodes. The obtained surface
      characteristics and stability were evaluated using contact angle measurements,
      XPS, AFM, and nanoindentation. For both materials, low water contact angles were
      found to correlate with high surface oxygen content. Only the surfaces exposed to
      relatively intense treatments, with self-bias voltages above 140 V (polystyrene)
      or 240 V (polycarbonate), could withstand washing in ethanol and remain highly
      hydrophilic. Substantial amounts of nonsoluble material were observed on the
      plastic substrates after treatment. Furthermore, for polycarbonate Young's
      modulus of the surface was found to increase with increasing intensity of the
      plasma. These observations were taken as an indication that extensive cross
      linking of the surface layer took place. After more than 6 months of storage, the
      samples treated with the most intense plasmas (self-bias voltages in the range of
      480-600 V) still had water contact angles around 20 degrees .

PMID- 16290406
TI  - Two-dimensional colloidal aggregation: concentration effects.
AB  - Extensive numerical simulations of diffusion-limited (DLCA) and reaction-limited
      (RLCA) colloidal aggregation in two dimensions were performed to elucidate the
      concentration dependence of the cluster fractal dimension and of the different
      average cluster sizes. Both on-lattice and off-lattice simulations were used to
      check the independence of our results on the simulational algorithms and on the
      space structure. The range in concentration studied spanned 2.5 orders of
      magnitude. In the DLCA case and in the flocculation regime, it was found that the
      fractal dimension shows a linear-type increase with the concentration phi,
      following the law: d(f)=d(fo)+aphi(c). For the on-lattice simulations the fractal
      dimension in the zero concentration limit, d(fo), was 1.451+/-0.002, while for
      the off-lattice simulations the same quantity took the value 1.445+/-0.003. The
      prefactor a and exponent c were for the on-lattice simulations equal to 0.633+/
      0.021 and 1.046+/-0.032, while for the off-lattice simulations they were 1.005+/
      0.059 and 0.999+/-0.045, respectively. For the exponents z and z', defining the
      increase of the weight-average (S(w)(t)) and number-average (S(n)(t)) cluster
      sizes as a function of time, we obtained in the DLCA case the laws:
      z=z(o)+bphi(d) and z'=z'(o)+b'phi(d'). For the on-lattice simulations, z(o), b,
      and d were equal to 0.593+/-0.008, 0.696+/-0.068, and 0.485+/-0.048,
      respectively, while for the off-lattice simulations they were 0.595+/-0.005,
      0.807+/-0.093, and 0.599+/-0.051. In the case of the exponent z', the quantities
      z'(o), b', and d' were, for the on-lattice simulations, equal to 0.615+/-0.004,
      0.814+/-0.081, and 0.620+/-0.043, respectively, while for the off-lattice
      algorithm they took the values 0.598+/-0.002, 0.855+/-0.035, and 0.610+/-0.018.
      In RLCA we have found again that the fractal dimension, in the flocculation
      regime, shows a similar linear-type increase with the concentration
      d(f)=d(fo)+aphi(c), with d(fo)=1.560+/-0.004, a=0.342+/-0.039, and c=1.000+/
      0.112. In this RLCA case it was not possible to find a straight line in the log
      log plots of S(w)(t) and S(n)(t) in the aggregation regime considered, and no
      exponents z and z' were defined. We argue however that for sufficiently long
      periods of time the cluster averages should tend to those for DLCA and,
      therefore, their exponents should coincide with z and z' of the DLCA case.
      Finally, we present the bell-shaped master curves for the scaling of the cluster
      size distribution function and their evolution when the concentration increases,
      for both the DLCA and RLCA cases.

PMID- 16290407
TI  - Activated carbon oxygen content influence on water and surfactant adsorption.
AB  - This research investigates the adsorption properties of three activated carbons
      (AC) derived from coconut, coal, and wood origin. Each carbon demonstrates
      different levels of resistance to 2 M NaOH treatment. The coconut AC offers the
      greatest and wood AC the least resistance. The influence of base treatment is
      mapped in terms of its effects on specific surface area, micropore volume, water
      adsorption, and dodecanoic acid adsorption from both water and 2 M NaOH solution.
      A linear relationship exists between the number of water molecules adsorbed at
      the B-point of the water adsorption isotherm and the oxygen content determined
      from elemental analysis. Surfactant adsorption isotherms from water and 2 M NaOH
      indicate that the AC oxygen content effects a greater dependence on affinity for
      surfactant than specific surface area and micropore volume. We show a linear
      relationship between the plateau amount of surfactant adsorbed and the AC oxygen
      content in both water and NaOH phases. The higher the AC oxygen content, the
      lower the amount of surfactant adsorbed. In contrast, no obvious relationship
      could be drawn between the surfactant amount adsorbed and the surface area.

PMID- 16290408
TI  - Automated video microscopic imaging and data acquisition system for colloid
      deposition measurements.
AB  - An optical video microscopic system and image processing and data extraction and
      manipulation routines are developed for in situ detailed quantification of the
      deposition of colloids onto an arbitrary surface and determining their
      concentration distribution across the bulk suspension. The system produces a
      relatively large field of view (approximately 330 x 245 microm) and utilizes dark
      field light microscopy to visualize colloids as small as approximately 0.3 microm
      in diameter at the surface and in the bulk suspension with a sufficient
      resolution (approximately 0.5 microm). On real-time basis, the routines automate
      various tasks from image capturing and processing to data manipulation,
      extraction, and display. The extracted data include: (i) surface concentration
      and flux of deposited, attached, and detached colloids, (ii) surface
      concentration and flux of arriving and departing colloids, (iii) distribution of
      colloids in the bulk suspension in the direction perpendicular to the deposition
      surface, and (iv) spatial and temporal distributions of deposited colloids. This
      article provides detailed description of the system and its image processing and
      data extraction and manipulation routines. Representative results of the
      deposition of 0.3-microm-diameter polystyrene colloids onto a glass surface, from
      a flowing suspension in a 0.02-cm-aperture parallel-plate channel, are presented
      and discussed.

PMID- 16290409
TI  - Kinetic study of metal biosorption to a brown alga, Kjellmaniella crassiforia.
AB  - A kinetic study of cadmium and lead biosorption to a brown alga, Kjellmaniella
      crassiforia, was carried out. The shrinking core model derived by M. Gopala Rao
      and A. K. Gupta (Chem. Eng. J.24, 181, (1982)) was modified and adapted for
      description of the rate process of cadmium and lead biosorption to the alga. The
      biosorption rate process was well described and average apparent diffusion
      coefficient of about 9 x 10(-6) cm(2) s(-1) was found for both cadmium and lead
      ions. The value was 20 to 50 times higher than the apparent diffusion
      coefficients of cadmium and lead ions in strong-acid resins like Dowex 50W-X8.

PMID- 16290410
TI  - Solid-phase extraction for the decontamination of alkali metal, alkaline Earth
      metal, and ammonium salts from heavy metal ions.
AB  - Salicylaldoxime-immobilized silica gel was characterized and used as a potential
      sorbent for heavy metal ions, viz. Cu(II), Ni(II), Co(II), and Zn(II). The
      experimental conditions were optimized both in batch and column processes to
      achieve the maximum efficiency. Kinetic and thermodynamic parameters as well as
      isotherm constants were evaluated to test the feasibility of the process. The
      role of various metal ions and different anions were tested in order to monitor
      the process in case of real samples. The alkali metal, alkaline earth metal, and
      ammonium salts do not have any effect on the said process. This differential
      behavior can be effectively used for the decontamination of alkali metal,
      alkaline earth metal, and ammonium salts from Cu(II), Ni(II), Co(II), and Zn(II)
      ions via solid phase extraction following AAS measurement. The purification of
      the salts was confirmed by voltammetric experiment.

PMID- 16290412
TI  - Aggregation of rhodamine 3B adsorbed in Wyoming Montmorillonite aqueous
      suspensions.
AB  - The adsorption of Rhodamine 3B (R3B) molecules in Wyoming Montmorillonite (Mont)
      particles suspended in water was studied by electronic absorption spectroscopy.
      Several adsorbed R3B species in the Mont tactoids were characterized from the
      observed changes in the absorption spectra by increasing the relative dye/clay
      concentration and the stirring time of the samples. R3B molecules can be adsorbed
      as monomeric units both in the water/clay interface and in the interlayer space,
      and head-to-tail R3B dimers and trimers were present in the external surface of
      Mont. The formation of internally adsorbed R3B monomers by the migration of the
      externally adsorbed species to the interlayer space leads to the deaggregation of
      the dye molecules in the external surface.

PMID- 16290411
TI  - Condensation of supersaturated n-butanol vapor on charged/neutral nanoparticles
      of D-mannose and L-rhamnose.
AB  - The effects of size, charge, and solubility on the condensation of supersaturated
      n-butanol vapor on monodisperse nanoparticles of D-mannose and L-rhamnose are
      investigated in a flow cloud chamber. The dependence of the critical
      supersaturation S(cr) on particle size in the range from 30 to 90 nm is
      determined experimentally. The results show that the experimental S(cr) decreases
      with increasing particle size and solubility, qualitatively in agreement with the
      prediction by the Volmer theory of nucleation on soluble particles and by the
      Kohler theory, but quantitatively smaller than both theoretical predictions. The
      condensation of supersaturated vapor on singly positive/negative charged
      particles with diameters of 30, 60, and 90 nm is examined, and no obvious charge
      effect and sign preference are observed.

PMID- 16290413
TI  - Spin probe study on the interaction of chitosan-derived polymer surfactants with
      lipid membrane.
AB  - Chitosan-derived polymer surfactants, sulfated N-acyl-chitosan (S-Cn-Chitosan),
      were synthesized and compared with commonly used low-molecular-weight
      surfactants, sodium dodecyl sulfate (SDS), dodecyltrimethyl ammonium chloride
      (DTAC), and octaethyleneglycol mono n-dodecyl ether (BL8SY), in their interaction
      with a lipid membrane using a spin probe method. A suspension of
      dipalmitoylphosphatidyl-choline (DPPC) spin-labeled strongly (10%) with a spin
      probe, 1-palmitoyl-2-(12-doxyl) stearoyl-phosphatidylcholine, was mixed with the
      surfactant solutions. The dissolution time of the DPPC membrane was estimated
      from the peak height change vs time, which was caused by the decrease in spin
      exchange interaction. The times were 2, 4, and 70 s for BL8SY, SDS, and DTAC and
      1.2 and 8.8 h for S-C10-Chitosan and S-C14-Chitosan, respectively, showing that
      the dissolution of the lipid membrane with polymer surfactants was far slower
      than that with low-molecular-weight surfactants. In addition, the time depended
      on the length of the alkyl chains of the polymer surfactants. Simulations of the
      ESR spectra of the DPPC-surfactant systems containing small amounts of
      surfactants were carried out in order to examine how the membrane structure was
      changed by the incorporation of surfactant molecules. By this analysis, it was
      revealed that the rigidity of the membrane was decreased by the addition of low
      molecular-weight surfactants in the order of DTAC>SDS>BL8SY, inverse to the order
      of dissolution times. S-Cn-Chitosan, in contrast, increased the rigidity of the
      membrane, suggesting that polymer surfactants adhered to the lipid membrane and
      tightly enfolded the riposome anchoring their alkyl chains.

PMID- 16290414
TI  - The effect of the water content of acetonitrile on the electrochemistry of
      ferrocenyl thiol self-assembled monolayers.
AB  - A novel kind of ethylene-ferrocenyl dodecyl thiol bearing an electron-withdrawing
      pyridium group (FcCH=CH-Py(CH2)10SH) was synthesized and mixed with HOOCC(10)SH
      on an Au electrode to form mixed self-assembled monolayers (SAMs) in ethanol
      solution. The influence of the water content of acetonitrile on the
      electrochemistry of the SAMs was studied by cyclic voltammetry and ac voltammetry
      measurement. The results showed that the current decreased and the oxidation
      potential of the ferrocene group shifted negatively with increasing water content
      of acetonitrile.

PMID- 16290415
TI  - The surface potential of a spherical colloid particle: functional theoretical
      approach.
AB  - By using the iterative method in functional analysis, the potential of the
      electrical double layer of a spherical colloid particle, which is represented by
      the so-called Poisson-Boltzmann (PB) equation, has been solved analytically under
      general potential conditions. With the help of the diagram method in mathematics,
      the surface potential of the particle has been defined from the second iterative
      solution. The influence of the parameters included in the solutions on the
      surface potential has been studied. The results show that the surface potential
      of the particle increases as the temperature of the system, the aggregation
      number, and the concentration of ions increase, but decreases with an increase in
      the dielectric constant and the valence of the ions. The corresponding space
      charge density also has been illustrated in this work.

PMID- 16290417
TI  - Molecular dynamics simulation of the association of nonpolar spheres in water.
AB  - We apply molecular dynamics (MD) simulations to the study of the association of
      nonpolar spheres of effective radii between 1.6 and 6.1 A dissolved in water. The
      constrained MD method is used to calculate the potential of mean force (PMF) of
      the interaction between spheres. The depth of the potential of mean force
      increases with increasing radius of the nonpolar sphere. Our results suggest that
      the PMF is largely governed by size or entropic effects, and that energetic
      effects associated with the breaking or distortion of hydrogen bonds are of minor
      importance.

PMID- 16290416
TI  - DLVO interactions of tungsten oxide and cobalt oxide surfaces measured with the
      colloidal probe technique.
AB  - We have investigated the DLVO surface forces of oxidized tungsten and cobalt
      surfaces using the atomic force microscope (AFM) colloidal probe technique. It
      was shown by X-ray photoelectron spectroscopy (XPS) and electrokinetic
      measurements that this model system is representative of industrial tungsten
      carbide (WC) and cobalt powders used in the production of hard metals. We found
      that the attractive van der Waals forces are well described by Hamaker constants,
      calculated from optical data for WO(3) and CoOOH. The repulsive electrostatic
      double layer forces between WO(3) surfaces increase with increasing pH due to an
      increasingly negative surface potential. This surface potential decreases with
      increasing ionic strength at pH 7.5. The electrostatic interaction between WO(3)
      and CoOOH is attractive at pH 10, suggesting a positively charged CoOOH surface.

PMID- 16290418
TI  - Modeling of interface phenomena in liquid under vibration, using the chemical
      model.
AB  - An analysis of interface phenomena in a liquid under a vibration field is
      presented, based on the chemical model of vibration in a liquid. The objects
      studied are a bubble, a solid surface, and a linear macromolecule, in a vibrated
      liquid. It is concluded that many sonochemical phenomena can be realized in some
      different (two or more) mechanisms, and mutually stimulate. Inharmonic effects
      and the influence of distant neighbors are analyzed.

PMID- 16290419
TI  - Electrochemical characterization of an asymmetric nanofiltration membrane with
      NaCl and KCl solutions: influence of membrane asymmetry on transport parameters.
AB  - Electrochemical characterization of a nanofiltration asymmetric membrane was
      carried out by measuring membrane potential, salt diffusion, and electrical
      parameters (membrane electrical resistance and capacitance) with the membrane in
      contact with NaCl and KCl solutions at different concentrations (10(-3)< or
      =c(M)< or =5 x 10(-2)). From these experiments characteristic parameters such as
      the effective concentration of charge in the membrane, ionic transport numbers,
      and salt and ionic permeabilities across the membrane were determined. Membrane
      electrical resistance and capacitance were obtained from impedance spectroscopy
      (IS) measurements by using equivalent circuits as models. This technique allows
      the determination of the electrical contribution associated with each sublayer;
      then, assuming that the dense sublayer behaves as a plane capacitor, its
      thickness can be estimated from the capacitance value. The influence of membrane
      asymmetry on transport parameters have been studied by carrying out measurements
      for the two opposite external conditions. Results show that membrane asymmetry
      strongly affects membrane potential, which is attributed to the Donnan exclusion
      when the solutions in contact with the dense layer have concentrations lower than
      the membrane fixed charge (X(ef) approximately -0.004 M), but for the reversal
      experimental condition (high concentration in contact with the membrane dense
      sublayer) the membrane potential is practically similar to the solution diffusion
      potential. The comparison of results obtained for both electrolytes agrees with
      the higher conductivity of KCl solutions. On the other hand, the influence of
      diffusion layers at the membrane/solution interfaces in salt permeation was also
      studied by measuring salt diffusion at a given NaCl concentration gradient but at
      five different solutions stirring rates.

PMID- 16290420
TI  - Monolayer formation of alkyl chain-containing phosphoric acid amphiphiles at the
      air/water (pH 5.6) interface: influence of temperature and cations.
AB  - In the four studied monoalkyl phosphoric acids (n-C(12)H(25)OPO(OH)(2), MDP; n
      C(14)H(29)OPO(OH)(2), MTP; n-C(16)H(33)OPO(OH)(2), MHP; and n
      C(18)H(37)OPO(OH)(2)MOP), only MOP can form an insoluble monolayer at the
      air/water interface (pH 5.6), suggesting that the longer alkyl chain (> or
      =C(18)) is essential for the formation of insoluble monolayers. On the contrary,
      all four corresponding dialkyl phosphoric acids ((n-C(12)H(25)O)(2)PO(OH), DDP;
      (n-C(14)H(29)O)(2)PO(OH), DTP; (n-C(16)H(33)O)(2)PO(OH), DHP; and (n
      C(18)H(37)O)(2)PO(OH) DOP) can form insoluble monolayers, with only the pi-A
      isotherm of DDP showing a phase transition plateau at 25 degrees C. The
      enhancement of the subphase temperature not only increases the plateau pressure
      of the DDP monolayer, but also induces the emergence of a plateau for the DTP
      monolayer. In contrast to the weak influence of Na(+) and K(+) (1 x 10(-4) M in
      the subphases, pH approximately 5.6) on the pi-A isotherm of DDP, Ca(2+), Sr(2+),
      and Ba(2+) (1 x 10(-4) M in the subphases, pH approximately 5.6) have an evident
      impact on the isotherms of DDP, and the different isotherm results indicate that
      DDP can recognize the three divalent cations at the air/water interface. In
      addition, the gaseous portion and phase transition plateaus of the isotherms of
      some DAPs on pure water and on subphases containing Ca(2+), Sr(2+), or Ba(2+)
      were well simulated by Volmer's equation of state and Vollhardt's equation,
      except for a small difference for gas phases around critical points. The
      relationship between the plateau and the net molecule area is also discussed.

PMID- 16290422
TI  - Fast transient fluorescence technique (FTRF) for studying vapor-induced latex
      film formation.
AB  - A fast transient fluorescence (FTRF) technique was used to study latex film
      formation induced by organic solvent vapor. Seven different films with the same
      latex content were prepared separately from poly(methyl methacrylate) (PMMA)
      particles and exposed to vapor of various chloroform-heptane mixtures in seven
      different experiments. Latex films were prepared from pyrene (Py)-labeled latex
      particles and fluorescence lifetimes of Py were monitored during vapor-induced
      film formation. It was observed that pyrene lifetimes decreased as vapor exposure
      time increased. A Stern-Volmer kinetic analysis was used for low quenching
      efficiencies to interpret the decrease in pyrene lifetimes. A Prager-Tirrel model
      was employed to obtain back-and-forth frequencies, nu, of the reptating PMMA
      chains during latex film formation induced by solvent vapor. nu values were found
      to be correlated with chloroform content in vapor mixture. It was observed that
      polymer interdiffusion obeyed a t(1/2) law during film formation. The results of
      optical transmission experiments were found to support these findings.

PMID- 16290421
TI  - Zirconium phosphate dispersed on a cellulose fiber surface: preparation,
      characterization, and selective adsorption of Li+, Na+, and K+ from aqueous
      solution.
AB  - Highly dispersed zirconium phosphate was prepared by reacting Cel/ZrO(2)
      (ZrO(2)=6.7 wt%; 0.56 mmol g(-1) of zirconium atom per gram of the material) with
      phosphoric acid. High power decoupling magic angle spinning (HPDEC-MAS)(31)P NMR
      and X-ray photoelectron spectroscopy data indicated that HPO(2-)(4) is the
      species present on the fiber surface. The X-ray diffraction patterns showed that
      zirconium hydrogen phosphate particles were amorphous and had an ion-exchange
      capacity, determined by ammonia gas adsorption, of 0.30 mmol g(-1). The ion
      exchange capacities for Li(+), Na(+), and K(+) ions were determined from ion
      exchange isotherms at 298 K and showed the following values (in mmol g(-1)):
      Li(+)=0.01, Na(+)=0.23, and K(+)=0.30. The higher affinity of the surface
      hydrogen phosphate particles for Na(+) and K(+) is due to its lamelar structure
      which permits easier diffusion of these two ions whose hydrated radii are smaller
      than that of Li(+).

PMID- 16290423
TI  - Numerical and similarity solutions for reversible population balance equations
      with size-dependent rates.
AB  - Population balance equations (PBEs) for reversible aggregation-fragmentation
      processes are important to particle agglomeration and dissolution, polymerization
      and degradation, liquid droplet coalescence and breakup, and floc coagulation and
      disintegration. Moment solutions provide convenient solutions to the PBEs,
      including steady state and similarity solutions, but may not be feasible for
      complex forms of size-dependent rate coefficients and stoichiometric kernels.
      Numeric solutions are thus necessary not only for applications, but also for the
      study of the mathematics of PBEs. Here we propose a numerical method to solve
      PBEs and compare the results to moment solutions. The numeric results are
      consistent with known steady state and asymptotic long-time similarity solutions
      and show how processes can be approximated by self-similar formulations.

PMID- 16290424
TI  - Studies on exchange equilibria of cations between cation-exchange membranes and
      electrolytic solutions.
AB  - The variations of the selectivity coefficient K(A)(B) between Na(+)-H(+), Na(+)
      K(+), and Na(+)-Cu(2+) systems and the separation factor alpha(A)(B) between
      Na(+)-Cu(2+) and K(+)-Cu(2+) systems in cation-exchange membranes as functions of
      loading and particle size of resin have been measured. The exchange affinities of
      all the membranes increase as H(+)<Na(+)<K(+)<Cu(2+). K(A)(B) is almost constant,
      independent of particle size and loading of resin in the membrane. Alpha(Na)(Cu)
      and alpha(K)(Cu) increase with decrease in particle size but remain almost
      constant with loading of resin in the membranes. The order of selectivity is
      K(Na)(H)<K(Na)(K)< or =K(Na)(Cu). The values of (alpha(A)(B)Q(0)(
      1))(other)(alpha(A)(B)Q(0)(-1))(-1)(M(300)C60) for the Na(+)-Cu(2+) system are
      approximately 1.060 and for K(+)-Cu(2+) are approximately 0.870. Q(0) represents
      the exchange capacity of a dry membrane per unit volume (in milliequivalents per
      cubic centimeter).

PMID- 16290425
TI  - Spreading of liquid drops over saturated porous layers.
AB  - Spreading of small liquid drops over thin porous layers saturated with the same
      liquid is investigated from both theoretical and experimental points of view. A
      theory is presented that shows that spreading is governed by the same power law
      as in the case of spreading over a dry solid substrate. The Brinkman's equations
      are used to model the liquid flow inside the porous substrate. An equation of the
      drop spreading is deduced, which shows that both an effective lubrication and the
      liquid exchange between the drop and the porous substrates are equally important.
      The presence of these two phenomena removes the well-known singularity at the
      moving three-phase contact line. Matching of the drop profile in the vicinity of
      the three-phase contact line with the main spherical part of the drop gives the
      possibility to calculate the pre-exponential factor in the spreading law via
      permeability and effective viscosity of the liquid in the porous layer.
      Unfortunately, the latter dependency turns out to be very weak. Spreading of
      silicone oils over different microfiltration membranes is carried out. Radii of
      spreading on time experimental dependencies confirm the theory predictions.
      Experimentally found coefficients agree with theoretical estimations.

PMID- 16290426
TI  - Heat evolution of micelle formation, dependence of enthalpy, and heat capacity on
      the surfactant chain length and head group.
AB  - Micelle formation by many surfactants is endothermic at low temperatures but
      exothermic at high temperatures. In this respect, dissociation of micelles
      (demicellization) is similar to dissolving hydrocarbons in water. However, a
      remarkable difference between the two processes is that dissolving hydrocarbons
      is isocaloric at about 25 degrees C, almost independently of the hydrocarbon
      chain length, whereas the temperature (T*) at which demicellization of different
      surfactants is athermal varies over a relatively large range. We have
      investigated the temperature dependence of the heat of demicellization of three
      alkylglucosides with hydrocarbon chains of 7, 8, and 9 carbon atoms. At about 25
      degrees C, the heat of demicellization of the three studied alkylglucosides
      varied within a relatively small range (DeltaH=-7.8+/-0.4 kJ/mol). The
      temperature dependence of DeltaH(demic) indicates that within the studied
      temperature range the heat capacity of demicellization (DeltaC(P,demic)) is about
      constant. The value of DeltaC(P,demic) exhibited an apparently linear dependence
      on the surfactant's chain length (DeltaC(P,demic)/n(CH(2))=47+/-7 kJ/mol K). Our
      interpretation of these results is that (i) the transfer of the head groups from
      micelles to water is exothermic and (ii) the temperature dependence of the heat
      associated with water-hydrocarbon interactions is only slightly affected by the
      head group. This implies that the deviation of the value of T* from 25 degrees C
      results from the contribution of the polar head to the overall heat of
      demicellization. Calorimetric studies of other series of amphiphiles will have to
      be conducted to test whether the latter conclusion is general.

PMID- 16290427
TI  - The role of the carboxylate head group in the interaction of sodium dodecanoate
      with poly(ethylene oxide) investigated by electrical conductivity, viscosity, and
      aggregation number measurements.
AB  - The binding of sodium dodecanoate (SDoD) to poly(ethylene oxide) (PEO) in aqueous
      solution was investigated and compared with the well-known polymer-surfactant
      complexes formed between PEO and sodium dodecyl sulfate (SDS). Electrical
      conductivity measurements indicated that the concentration ratio of bound SDoD to
      PEO (on monomer basis) was greater than that for the system PEO-SDS. However, the
      aggregation numbers of the micelles supported on the polymer chain are
      practically constant and similar for both surfactants at concentrations lower
      than the polymer saturation point. The difference in binding capability is
      explained in terms of a larger PEO coil expansion upon complexation of SDoD than
      in the case of SDS. An increase in the polymer surface favors the binding of SDoD
      to PEO in aqueous solution. This conclusion is supported by the results of the
      viscometric studies of PEO-surfactant solution.

PMID- 16290428
TI  - Scaling analysis of coating of a plate or a fiber.
AB  - The problem of coating a plate or a fiber through their withdrawal from a large
      reservoir was treated in the literature in various limiting cases. In the present
      paper, interpolation expressions are derived by scaling for Newtonian, Bingham,
      and viscoelastic fluids. The scaling analysis was also employed to explain the
      sharp increase in film thickness produced by inertia and the occurrence of a
      maximum thickness for an optimum velocity. It is also shown that, for a
      viscoelastic fluid, the film thickness tends to a finite value at very large
      withdrawal rates. An explanation is also provided for the existence of a maximum
      film thickness for an optimum surfactant concentration.

PMID- 16290430
TI  - On visualization of sub-micron particles with dark-field light microscopy.
AB  - Dark-field light microscopy is widely employed to visualize colloidal particles
      much smaller than the light wavelength used. In the captured images, the
      colloidal particles appear, against a dark background, as bright "specks" much
      larger than the geometrical size of the particles. To verify whether the "specks"
      are for individual particles or clusters of particles, experiments are performed
      which used low bulk concentrations of five suspensions of monodispersed particles
      (approximately 0.3 microm in diameter) and a dark-field video microscopic system
      with an optical resolution of approximately 0.5 microm to count the particles
      after they all have deposited onto the inner surfaces of a parallel-plate glass
      channel. The average size and the size distribution of the particles are also
      determined at the end of each experiment. The results confirmed that the
      visualized "specks" are for individual particles. The measured and prepared
      particle bulk concentrations in the five experiments closely matched, to within
      +/-5%, and the measured average size of the particles and their size distribution
      at the end of the five experiments were in agreement with the known values.

PMID- 16290429
TI  - Effect of TiO2 colloids on the fluorescence behavior of two cyanine dyes.
AB  - The photophysical properties of two typical cyanine dyes [3,3'-diethyl-9-methyl
      thiacarbocyanine iodide (dye A) and anhydro-3,3'-disulfopropyl-5,5'-diphenyl-9
      ethyloxacarbocyanine hydroxide (dye B)] in the absence and presence of TiO(2)
      colloids have been investigated by UV-visible spectroscopy, (1)H-NMR
      spectroscopy, fluorescence spectroscopy, fluorescence lifetime measurements, and
      ESR measurements. It was found from the absorption spectra and NMR results that
      there are two isomers in the ground state of these dyes. Steady-state
      fluorescence spectra show that the fluorescence intensities of dye A and dye B
      are enhanced and quenched by TiO(2) colloids, respectively. Time-resolved
      fluorescence lifetime measurements indicate that the lifetimes of dye A and dye B
      in the presence of TiO(2) colloids are longer and shorter than those obtained in
      the absence of TiO(2) colloids, respectively. ESR measurements demonstrate that
      the electron transfer efficiency from (1)dye B* to the conduction band of TiO(2)
      is much larger than that from (1)dye A* to the conduction band of TiO(2). The
      different fluorescence behavior of dye A and dye B can be intepreted in terms of
      whether phi(Tr,nr)(0)-phi(Tr,nr) (the reduction of the quantum yield for
      radiationless transition in the excited singlet state (1)dye* caused by the
      TiO(2) colloids) is larger or smaller than phi(ET) (the quantum yield of electron
      transfer from (1)dye* to the conduction band of TiO(2) colloids).

PMID- 16290431
TI  - Preparation of ZnS nanorods by a liquid crystal template.
AB  - ZnS nanorods were synthesized in lamellar liquid crystals of C(12)E(4) by mixing
      zinc ions and thioacetamide (TAA) solution. The effects of the reactant
      concentration and the surfactant/water molar ratio in the liquid crystal system
      on the morphology and size of the ZnS particles were investigated. The prepared
      ZnS particles are regular nanorods having a width of about 60 nm and a length of
      about 80-380 nm, with a largest aspect ratio of about 6.3. A lamellar liquid
      crystal templating mechanism has been proposed to interpret the experimental
      results.

PMID- 16290434
TI  - Calculation and prediction of adsorption excesses on the ternary liquid
      mixture/air interface from surface tension measurements.
AB  - The surface tensions of the n-propanol/ethylene glycol/water ternary mixture and
      its binary mixtures are measured at 293 K and described by mathematical
      functions. The experimental data and their descriptions are shown in the three
      dimensional space by means of coordinate transformation. A thermodynamic model to
      calculate and predict ternary adsorption excess data on the ternary liquid
      mixture/air interface from surface tensions is presented. The calculated
      adsorption excess data in the ternary triangle are discussed.

PMID- 16290435
TI  - Some peculiarities in the specific adsorption of phosphate ions on hematite and
      gamma-Al2O3 as reflected by radiotracer studies.
AB  - The specific adsorption of radiolabeled phosphate ions from perchlorate
      supporting electrolyte onto gamma-Al2O3 and hematite powder has been
      investigated. The pH dependence of the adsorption of phosphate species was
      compared with that of sulfate ions. It was demonstrated that in contrast to the
      behavior of sulfate ions the pH dependence of phosphate ions goes through a
      maximum. On the other hand, it was found that the reversible adsorption of
      phosphate ions is accompanied by the formation of strongly chemisorbed species.
      Results obtained from a study of the competitive adsorption of sulfate and
      phosphate ions at various pH values are reported and interpreted. An attempt is
      made to correlate the experimental findings with the models for anion adsorption
      reported in the literature.

PMID- 16290436
TI  - Surface charge density/surface potential relationship for a spherical colloidal
      particle in a salt-free medium.
AB  - On the basis of a theory of Imai and Oosawa (Busseiron Kenkyu52, 42 (1952); 59,
      99 (1953)), approximate analytic expressions for the surface charge
      density/surface potential relationship for a spherical colloidal particle in a
      salt-free (aqueous or nonaqueous) medium containing only counterions are derived.
      There is a certain critical value of the surface charge density (or the total
      surface charge) separating two distinct cases: low surface charge density case
      and high surface charge density case. In the latter case counterion condensation
      occurs in the vicinity of the particle surface. The results are in excellent
      agreement with numerical calculations for the case of dilute suspensions.

PMID- 16290437
TI  - The effect of molecular weight of nonadsorbing polymer on the structure of
      depletion-induced flocs.
AB  - This work explores the structural compactness of depletion-induced particle flocs
      with respect to the molecular weight of nonadsorbing polymer flocculants. Small
      angle static light scattering was used to monitor the structural characteristics
      of the flocs, which were formed by the addition of nonadsorbing poly(acrylic
      acids) to a stable colloidal polystyrene latex dispersion. It was found that the
      floc mass fractal dimension, considered to be a measure of structural
      compactness, was dependent upon both the molecular weight and the concentration
      of the polyacid. In particular, reducing the molecular weight of the polymer at a
      fixed polyacid concentration resulted in higher mass fractal dimensions, despite
      the highly polydisperse nature of the polymer samples. This structural behavior
      was attributed to the lower particle sticking efficiencies upon collision. This
      reduced sticking ability is the result of the shallowing in the secondary
      potential energy well with decreasing polymer chain length, which was directly
      supported by atomic force microscopy data. Our results suggest that the formation
      of a shallower attraction well with a lower molecular weight nonadsorbing polymer
      is the result of the insufficiency of the increased osmotic pressure to counter
      balance the short-ranged nature of the depletion interaction.

PMID- 16290438
TI  - Cluster-cluster aggregation kinetics and primary particle growth of soot
      nanoparticles in flame by light scattering and numerical simulations.
AB  - The agglomeration kinetics of growing soot generated in a diffusion atmospheric
      flame are here studied in situ by light scattering technique to infer cluster
      morphology and size (fractal dimension D(f) and radius of gyration R(g)). SEM
      analysis is used as a standard reference to obtain primary particle size D(P) at
      different residence times. The number N(P) of primary particles per aggregate and
      the number concentration n(A) of clusters are evaluated on the basis of the
      measured angular patterns of the scattered light intensity. The major finding is
      that the kinetics of the coagulation process that yields to the formation of
      chain-like aggregates by soot primary particles (size 10 to 40 nm) can be
      described with a constant coagulation kernel beta(c,exp)=2.37x10(-9) cm3/s
      (coagulation constant tau(c) approximately = 0.28 ms). This result is in nice
      accord with the Smoluchowski coagulation equation in the free molecular regime,
      and, vice versa, it is in contrast with previous studies conducted by invasive
      (ex situ) techniques, which claimed the evidence in flames of coagulation rates
      much larger than the kinetic theory predictions. Thereafter, a number of
      numerical simulations is implemented to compare with the experimental results on
      primary particle growth rate and on the process of aggregate reshaping that is
      observed by light scattering at later residence times. The restructuring process
      is conjectured to occur, for not well understood reasons, as a direct consequence
      of the atomic rearrangement in the solid phase carbon due to the prolonged
      residence time within the flame. Thus, on one side, it is shown that the
      numerical simulations of primary size history compare well with the values of
      primary size from SEM experiment with a growth rate constant of primary diameter
      about 1 nm/s. On the other side, the evolution of aggregate morphology is found
      to be predictable by the numerical simulations when the onset of a first-order
      "thermal" restructuring mechanism is assumed to occur in the flame at about 20 ms
      residence time leading to aggregates with an asymptotic fractal dimension
      D(f,infinity) approximately = 2.5.

PMID- 16290439
TI  - Preparation of cadmium sulfide nanoparticles in self-reproducing reversed
      micelles.
AB  - Octyl octanoate (O-OL) underwent hydrolysis in sodium octanoate (NaOA) reversed
      micelles in 85:15 = isooctane:octanol (OL) (v/v), containing w = [H2O]/[NaOA] =
      40. The products of the hydrolysis, octanoic acid (OA) and octanol (OL), lead to
      the formation of additional (albeit smaller) reversed micelles; hence the process
      is considered to be self-reproducing. Self-reproduction was found to be catalyzed
      by lithium hydroxide, solubilized in the water pools, as well as by hydrogen
      sulfide, added to the solution of the reversed micelles. Addition of hydrogen
      sulfide to cadmium perchlorate containing self-reproducing reversed micelles
      resulted in the formation of cadmium sulfide (CdS) nanoparticles. Diameters of
      the CdS containing nanoparticles could be altered from 5.4 to 1.8 nm by changing
      the [Cd2+]/[H2S] ratios from 0.25 to 10. The CdS nanoparticles formed were capped
      by mercaptopropionic acid, isolated as solids, and could be repeatedly
      redispersed in water without changing their sizes. Additional CdS nanoparticles
      were generated in the supernatants removed from the precipitated capped CdS
      nanoparticles.

PMID- 16290440
TI  - Partitioning of clay colloids at air-water interfaces.
AB  - Colloid sorption onto air-water interfaces in a variety of natural environments
      has been previously recognized, but better quantification and understanding is
      still needed. Affinities of clay colloids for the air-water interface were
      measured using a bubble-column method and reported as partition coefficients (K).
      Four types of dilute clay suspensions were measured in NaCl solutions under
      varying pH and ionic strength conditions: kaolinite KGa-1, illite IMt-2,
      montmorillonite SWy-2, and bentonite. The K values of three types of polystyrene
      latex particles with different surface-charge properties were also measured for
      comparison. Kaolinite exhibited extremely high affinity to the air-water
      interface at pH values below 7. Illite has lower affinity to air-water interfaces
      than kaolinite, but has similar pH dependence. Na-montmorillonite and bentonite
      clay were found excluded from the air-water interface at any given pH and ionic
      strength. Positively and negatively charged latex particles exhibited sorption
      and exclusion, respectively, at the air-water interface. These results show the
      importance of electrostatic interactions between the air-water interface and
      colloids, especially the influence of pH-dependent edge charges, and influence of
      particle shape.

PMID- 16290441
TI  - Solution of the nonlinear Poisson-Boltzmann equation using pseudo-transient
      continuation and the finite element method.
AB  - The nonlinear Poisson-Boltzmann (PB) equation is solved using Newton-Krylov
      iterations coupled with pseudo-transient continuation. The PB potential is used
      to compute the electrostatic energy and evaluate the force on a user-specified
      contour. The PB solver is embedded in a existing, 3D, massively parallel,
      unstructured-grid, finite element code. Either Dirichlet or mixed boundary
      conditions are allowed. The latter specifies surface charges, approximates far
      field conditions, or linearizes conditions "regulating" the surface charge.
      Stability and robustness are proved using results for backward Euler differencing
      of diffusion equations. Potentials and energies of charged spheres and plates are
      computed and results compared to analysis. An approximation to the potential of
      the nonlinear, spherical charge is derived by combining two analytic formulae.
      The potential and force due to a conical probe interacting with a flat plate are
      computed for two types of boundary conditions: constant potential and constant
      charge. The second case is compared with direct force measurements by chemical
      force microscopy. The problem is highly nonlinear-surface potentials of the
      linear and nonlinear PB equations differ by over an order of magnitude.
      Comparison of the simulated and experimentally measured forces shows that
      approximately half of the surface carboxylic acid groups, of density 1/(0.2 nm2),
      ionize in the electrolyte implying surface charges of 0.4 C/m2, surface
      potentials of 0.27 V, and a force of 0.6 nN when the probe and plate are 8.7 nm
      apart.

PMID- 16290442
TI  - Disjoining pressure of thin nonfreezing interlayers.
AB  - At subzero temperatures, it has been found that nonfreezing water interlayers
      form between the inner smooth surface of a thin quartz capillary and the ice in
      the capillary core. The dilatometry method has been used to measure the
      thicknesses of these nonfreezing interlayers over a range of temperatures between
      -1 and -0.14 degrees C and for applied pressures up to 8 MPa. The measured data
      are used to calculate the disjoining pressure isotherms of nonfreezing water
      interlayers. It is shown that structural forces caused by structural changes of
      nonfreezing water are the main contribution to the disjoining pressure. The
      structural changes are also responsible for the phenomenon of the nonfreezing
      interlayers.

PMID- 16290443
TI  - Pull-off force measurements between rough surfaces by atomic force microscopy.
AB  - Direct measurements of the pull-off (adhesion) forces between pharmaceutical
      particles (beclomethasone dipropionate, a peptide-type material, and lactose)
      with irregular geometry and rough polymeric surfaces (series of polypropylene
      coatings, polycarbonate, and acrylonitrile-butadiene-styrene) were carried out
      using the atomic force microscope. These measurements showed that roughness of
      the interacting surfaces is the significant factor affecting experimentally
      measured pull-off forces. A broad distribution of pull-off force values was noted
      in the measurements, caused by a varying adhesive contact area for a particle
      located on rough substrate. The possibility of multiple points of contact between
      irregularly shaped pharmaceutical particles and substrate surfaces is
      demonstrated with nanoindentations of the particle in a fluoro-polymer film.
      Force-distance curves showing the "sawtooth" pattern are additional evidence that
      particles make contact with substrates at more than one point. Reduced adhesion
      of 10- to 14-microm-diameter lactose and peptide material particles to the
      polypropylene coatings with a roughness of 194 nm was found in this study.
      Similar pull-off force versus roughness relationships are also reported for the
      model spherical particles, silanized glass particle with a size of 10 microm and
      polystyrene particle with a diameter of 9 microm, in contact with polypropylene
      coatings of varying roughness characteristics. It was found that the model
      recently proposed by Rabinovich et al. (J. Colloid Interface Sci. 232, 1-16
      (2000)) closely predicts the pull-off forces for glass and lactose particles. On
      the other hand, the adhesion of the peptide material and polystyrene particle to
      polypropylene is underestimated by about an order of magnitude with the
      theoretical model, in which the interacting substrates are treated as rigid
      materials. The underestimate is attributed to the deformation of the peptide
      material and polystyrene particles.

PMID- 16290444
TI  - An investigation of submicrostructural evolution of freshly precipitated ZrO2 in
      digestion for ultrafine sulfated ZrO2 catalysts by SAXS technique.
AB  - Coupled with XRD, BET, and TEM, the small-angle X-ray scattering (SAXS) technique
      has been effectively used to probe and characterize the submicrostructure of
      freshly precipitated hydrous zirconia and its evolution during digestion. It has
      been found that fresh hydrous zirconia particles possess an average diameter of
      about 5 nm and rather rough surfaces describable in terms of fractal concepts.
      The digestion of zirconia precipitates at 100 degrees C with their mother liquors
      may remarkably smooth the particles' rough surface and provoke fractal
      aggregation of the particles but make little change in average particle
      dimensions. A local dissolution-reprecipitation mechanism is regarded as a basic
      process to accompany particle surface smoothing, particle aggregation, and
      coarsening at the neck areas between joint particles, which may greatly
      strengthen the particle networks and enhance their resistance to crumbling while
      calcinated at high temperatures. On the basis of the submicrostructural features
      unraveled by SAXS, a coherent and significant physical picture has been raised
      out to demonstrate and interpret the relationship underlying the
      submicrostructure, the surface area variation, and the heating behavior of
      hydrous zirconia precipitates.

PMID- 16290445
TI  - Mineral matter distribution on coal surface and its effect on coal wettability.
AB  - Coal is an organic sedimentary rock composed of organic macerals and mineral
      matter. As it is demonstrated in this paper the discrete mineralogical nature of
      coal largely influences the wetting of the coal surface by water. Both advancing
      and receding contact angles were measured using the captive-bubble technique with
      an automatic bubble shape analysis software. The distribution and amount of
      mineral inclusions on the coal surface were determined by scanning electron
      microscopy and examined using the image analysis system. To determine the amount
      and size distribution of mineral grains, the coal surface layer, on which the
      contact angles were measured, was separated from the larger piece used in the
      measurements by microslicing. The separated surface layer was subjected to a low
      temperature ashing followed by particle size analysis. As expected, a significant
      scatter of contact angle values was obtained for the same coal samples.
      Increasing the amount of mineral matter on the coal surface reduced the value of
      both advancing and receding contact angles. Also, the scatter of contact angle
      values increased with the increasing mineral matter content from about 1 to 50
      wt%. The results reveal that an important factor in analysis of contact angle
      variation on coal surfaces is the size of the hydrophilic mineral inclusions.
      Both the advancing and the receding contact angles decrease with increasing size
      of the mineral grains. Additionally, the scatter of contact angle values increase
      with increasing size of the mineral matter grains. Finally, the results of
      fractal dimension analysis of mineral matter grains distributed over the coal
      surface indicate that there is no significant effect from the shape of
      hydrophilic mineral inclusions on both advancing and receding contact angles.

PMID- 16290446
TI  - Dynamic properties of poly(styrene)-poly(ethylene oxide) diblock copolymer films
      at the air-water interface.
AB  - The complex dynamic elasticity of monolayers of the diblock copolymer
      poly(styrene)-poly(ethylene oxide) at the air-water interface in the pancake,
      quasi-brush, and brush regimes has been studied by means of three experimental
      techniques--the surface transverse and longitudinal waves and the oscillating
      barrier method. In the pancake regime the surface viscoelastic properties in the
      frequency range under investigation (0.01-520 Hz) prove to be indistinguishable
      from the surface properties of the homopolymer PEO. Transition to the quasi-brush
      regime is accompanied by rather abrupt changes in both components of the surface
      viscoelasticity. The surface viscosity in the brush regime exceeds significantly
      the results calculated from the theory of D. M. A. Buzza et al. (J. Chem.
      Phys.109, 5008 (1998)), which takes into account the dissipation arising from the
      flow of solvent through the brush phase. Possible reasons of this discrepancy are
      discussed.

PMID- 16290447
TI  - Monitoring entering and spreading of emulsion droplets at an expanding air/water
      interface: a novel technique.
AB  - The entering and spreading of emulsion droplets at quiescent and expanding
      air/water interfaces was studied using a new apparatus consisting of a modified
      Langmuir trough in which the air/water interface can be continuously expanded by
      means of rollers in the place of traditional barriers. When sodium caseinate and
      whey protein isolate-stabilized emulsion droplets were injected under the surface
      of sodium caseinate and whey protein isolate solutions, respectively, it appeared
      that the droplets entered the air/water interface only if the air/water surface
      pressure did not exceed a threshold value of approximately 15 mN/m. This
      condition was satisfied either under quiescent conditions for low protein
      concentrations or by continuous expansion of the interface at higher protein
      concentrations. According to equilibrium thermodynamics, entering of the droplets
      and the formation of lenses should occur for all the systems investigated, but
      this was not observed. At surface pressures higher than approximately 15 mN/m,
      immersed emulsion droplets were metastable. This is probably due to a kinetic
      barrier caused by the formation of a thin water film bounded by protein
      adsorption layers between the emulsion droplet and the air/water interface.

PMID- 16290448
TI  - A crystallite packing model for pseudoboehmite formed during the hydrolysis of
      trisecbutoxyaluminium to explain the peptizability.
AB  - A model for pseudoboehmite crystallite packing formed during the hydrolysis of
      trisecbutoxyaluminium is postulated. The model describes platelike crystallites
      of pseudoboehmite stacked in a sharing edges only configuration. With this type
      of stacking, the pore sizes detected are approximately equal to the crystallite
      sizes of the hydrolysates. The hydrolysates age via a dissolution re
      precipitation reaction. This increases the size of the crystallite size of the
      pseudoboehmite formed, speeding peptization by allowing nitrate ions to enter
      pores and access the surfaces of the crystallites. This type of model also allows
      an explanation for the peptization kinetics of systems containing sec-butanol
      formed during the hydrolysis of trisecbutoxyaluminium.

PMID- 16290449
TI  - Current-voltage curves for a cation-exchange membrane in methanol-water
      electrolyte solutions.
AB  - The current-voltage curves for a cation-exchange membrane separating two equal
      methanol-water electrolyte solutions were determined under different experimental
      conditions. From these curves, the values of the limiting current density, I(L),
      were determined. The influence of the volume percentage of methanol in the
      solvent on the results was analyzed. The presence of methanol in the solutions
      was shown not to affect the shape of the current-voltage curves typical of
      aqueous solutions. However, the system resistance and the values of the limiting
      current density were both greatly influenced by the content of methanol. Thus,
      the value of the resistance increased and the limiting current decreased with
      increasing methanol content of the solution.

PMID- 16290450
TI  - Effect of hydration of polyamide membranes on the surface electrokinetic
      parameters: surface characterization by x-ray photoelectronic spectroscopy and
      atomic force microscopy.
AB  - The surface and the solid/liquid interface of two polyamide membranes, one
      experimental (B0) and one commercial (NF45), have been characterized by X-ray
      photoelectronic spectroscopy (XPS), atomic force microscopy (AFM), and zeta
      potential, respectively. The surface roughness, determined by AFM data analysis,
      is different for the two membranes, and results show that the commercial NF45
      membrane presents a much lower roughness than the experimental B0 membrane. XPS
      data indicate that the surface of membrane NF45 is similar to that of pure
      polyamide, while membrane B0 contains a considerable amount of impurities. The
      homogeneity in depth of both membranes was also studied by determining the
      composition profile at different analysis angles. Streaming potential along the
      membrane surface or tangential streaming potential (TSP) measurements with NaCl
      solutions at different concentrations were carried out with both membranes to
      determine the zeta potential and the electrokinetic surface charge density, and a
      correlation between membrane surface and interface parameters is made. Some
      differences in atomic concentrations of membrane surface elements and X-ray
      photoelectronic spectra of the samples used in TSP measurements and after a
      drying process at 90 degrees C for 24 h can be observed when they are compared
      with those for fresh membranes. Electrokinetic parameters for membrane NF45 (TSP,
      zeta potential, and surface electrokinetic charge density) obtained from three
      different series of measurements strongly decrease as a result of membrane use,
      but for membrane B0 they are practically independent of the number of
      measurements. This difference in the electrokinetic behavior of the two membranes
      has been related to the hydration process of the surface for each sample studied
      by XPS and AFM.

PMID- 16290451
TI  - Influence of surface composition on hydrogen peroxide decomposition catalyzed by
      Co(II) aminopyridine-supported compounds on amorphous silica gel.
AB  - Cobalt compounds supported on 2-, 3-, and 4-aminopyridine-modified silica
      surfaces, named Sil2Co, Sil3Co, and Sil4Co, respectively, were used to catalyze
      the decomposition of hydrogen peroxide on ethanolic solutions at 293, 298, and
      303 K. The calculated k values (x10(-4) s(-1)) for Sil2Co, Sil3Co, and Sil4Co are
      0.65, 1.24, and 4.78 (293 K); 1.23, 1.87, and 6.33 (298 K); and 1.80, 2.80, and
      10.30 (303 K), respectively. All obtained results evidence that such
      decomposition is a first-order reaction. Zinc-, nickel-, and copper-supported
      compounds were also tested, but exhibited a very low catalytic activity. By using
      the k values at 298 and 303 K, and employing the equation ln (k1/k2) =
      E(a)/R(1/T2-1/T1), the activation energy values for the considered reaction were
      Sil2Co = 57.20, Sil3Co = 60.60, and Sil4Co = 73.10 kJ mol(-1), respectively. The
      low values calculated for E(a) are in agreement with a free-radical mechanism.

PMID- 16290452
TI  - Rise of liquids and bubbles in angular capillary tubes.
AB  - We discuss the rise of a liquid inside an angular capillary tube. It is shown
      that for a wetting liquid, the height of the rise is (as usually) inversely
      proportional to the length which characterizes the confinement. The exact laws
      deduced from energetic considerations are found to be in excellent agreement with
      the data. We then show how such tubes can be used to prevent bubbles from being
      trapped. The rising velocity of a bubble is finally discussed, in the particular
      case of a square tube.

PMID- 16290453
TI  - Influence of oil polarity on droplet growth in oil-in-water emulsions stabilized
      by a weakly adsorbing biopolymer or a nonionic surfactant.
AB  - The influence of oil type (n-hexadecane, 1-decanol, n-decane), droplet
      composition (hexadecane:decanol), and emulsifier type (Tween 20, gum arabic) on
      droplet growth in oil-in-water emulsions was studied. Droplet size distributions
      of emulsions were measured over time (0-120 h) by laser diffraction and
      ultrasonic spectroscopy. Emulsions containing oil molecules of low polarity and
      low water solubility (hexadecane) were stable to droplet growth, irrespective of
      the emulsifier used to stabilize the droplets. Emulsions containing oil molecules
      of low polarity and relatively high water solubility (decane) were stable to
      coalescence, but unstable to Ostwald ripening, irrespective of emulsifier.
      Droplet growth in emulsions containing oil molecules of relatively high polarity
      and high water solubility (decanol) depended on emulsifier type. Decanol droplets
      stabilized by Tween 20 were stable to droplet growth in concentrated emulsions
      but unstable when the emulsions were diluted. Decanol droplets stabilized by gum
      arabic exhibited rapid and extensive droplet growth, probably due to a
      combination of Ostwald ripening and coalescence. We proposed that coalescence was
      caused by the relatively low interfacial tension at the decanol-water boundary,
      which meant that the gum arabic did not absorb strongly to the droplet surfaces
      and therefore did not prevent the droplets from coming into close proximity.

PMID- 16290454
TI  - Characterization of the emulsification properties of 2S albumins from sunflower
      seed.
AB  - The ability of 2S albumins from sunflower seeds to stabilize oil-in-water
      emulsions has been investigated, demonstrating that one of the proteins (SFA8)
      effectively stabilizes emulsions, while another (SF-LTP) does not stabilize
      emulsions. The surface tension and surface dilation viscosity of these two
      proteins were measured, rationalizing the emulsifying ability of SFA8 in terms of
      its ability to form a strongly elastic monolayer at interfaces. The secondary
      structure changes that occur upon adsorption of SFA8 to the oil/water interface
      have also been studied by fluorescence, circular dichroism (CD), and Fourier
      transform infrared (FT-IR) spectroscopy. It was found that the beta-sheet content
      of the protein increased upon adsorption at the expense of alpha-helix and random
      structure. Moreover, FT-IR measurements indicate the presence of intermolecular
      beta-sheet formation upon adsorption. Fluorescence studies with an oil-soluble
      fluorescence quencher indicate that the single tryptophan residue present in SFA8
      may become located in the oil-phase of the emulsion. This residue is thought to
      be partially buried in the native protein, and these data suggest that changes in
      the polypeptide region flanking this residue may play an important role in the
      molecular rearrangement that occur on or following adsorption to the oil/water
      interface.

PMID- 16290455
TI  - Thermotropic behavior of poly(oxyethylene) cholesterol ethers.
AB  - The thermotropic behavior of poly(oxyethylene) cholesterol ether surfactants was
      studied by differential scanning calorimetry and small-angle X-ray scattering.
      Contrary to what is usually observed in conventional poly(oxyethylene)-type
      surfactant systems, poly(oxyethylene) cholesterol ether surfactants show a change
      of the fusion mechanism as the chain length is varied. For long chain lengths (n
      > or = 15) the usual solid-liquid transition is found, but for short chain
      lengths (n < or = 10) the transition goes through a birefringent lamellar phase.
      The appearance of this liquid crystal (LC) phase seems to be related with the
      predominance of the cholesterol part in the short chain polyoxyethylene
      surfactants. On the contrary, for long polyexyethylene chains the polymer gains
      in importance and only a solid crystalline structure is observed at low
      temperatures. An antiparallel packing structure with totally overlapped chains is
      found for both, the solid and the LC phase. The chains seem to be in a zigzag
      configuration, and only for the longest surfactant here studied (n = 30) a change
      of the chain configuration to a much shorter meander configuration is observed.

PMID- 16290456
TI  - Adsorption behavior of oxyethylated surfactants at the air/water interface.
AB  - Literature data for homologous series of nonionic and ionic surfactants, such as
      C(n)OH, C(n)EO(m), Tritons, C(n)SO4Na, and C(n)EO(m)SO4Na, were analyzed on the
      basis of the Frumkin and reorientation models. The thermodynamic quantities
      obtained from the reorientation model agree best with the experimental data. They
      yield the standard free energy of adsorption which can be split into
      contributions from the alkyl chain, and the polar head group. An additional
      contribution to the increment of the polar group deltaG0(P) from m EO groups
      deltaG0(EO(m)) is extracted which can be accounted for by deltaG0(EO(m)) = -2.35
      square root(m) kJ/mol. The standard free energy of adsorption is well understood
      by the increment method used.

PMID- 16290457
TI  - Polarizable particle aggregation under rotating magnetic fields using scattering
      dichroism.
AB  - We used scattering dichroism to study the dynamics of dipolar chains induced in
      magnetorheological suspensions under rotating magnetic fields. Both the dichroism
      (proportional to the total number of aggregated particles) and the phase lag show
      different behavior below and above a cross-over frequency. The cross-over
      frequency depends linearly on both the square of the magnetization and the
      inverse of the viscosity. The Mason number (ratio of viscous to magnetic forces)
      governs the dynamics. Therefore, there is a cross-over Mason number below which
      the dichroism remains almost constant and above which the rotation of the field
      prevents the particle aggregation process from taking place. Our experimental
      results have been compared with particle dynamics simulations showing good
      agreement.

PMID- 16290458
TI  - A model to describe the settling behavior of fractal aggregates.
AB  - A model to predict fractal dimension from sedimentating fractal aggregates has
      been successfully developed. This model was developed using the settling rate and
      size data of fractal aggregates. In order to test the validity of the model, a
      purpose-built settling rig, equipped with lens with magnification of 1200x, which
      can capture images of particles/flocs down to 2 microm in diameter was used. The
      performance and technique of the settling rig were validated by comparing the
      measured settling rates of 30- and 50.7-microm standard particles with their
      theoretical settling rates calculated using Stokes' law. The measured settling
      rates were within 10% agreement with the calculated Stokes' velocities. The
      settling rates and sizes of the particles/flocs were analyzed using image
      analysis software called WiT 5.3. The maximum temperature gradient across the
      settling column was 0.1 degrees C, which effectively eliminated convective
      currents due to temperature differences in the settling column. A total of 1000
      calcium phosphate flocs were analyzed. Calcium phosphate flocs with fractal
      dimensions varying from 2.3 to 2.8 were generated via orthokinetic aggregation.
      Measurements of fractal dimensions, using light scattering, were done
      simultaneously with the settling experiments and they were found to be constant.
      The fractal dimensions calculated using the model agreed with those obtained by
      light scattering to within 12%.

PMID- 16290459
TI  - The relationship between polymer/substrate charge density and charge
      overcompensation by adsorbed polyelectrolyte layers.
AB  - This work examines polyelectrolyte adsorption (exclusively driven by
      electrostatic attractions) for a model system (DMAEMA, polydimethylaminoethyl
      methacrylate, adsorbing onto silica) where the adsorbing polycation is more
      densely charged than the substrate. Variations in the relative charge densities
      of the polymer and substrate are accomplished by pH, and the polycation is of
      sufficiently low molecular weight that the adsorbed conformation is generally
      flat under all conditions examined. We demonstrate, quantitatively, that the
      charge overcompensation observed on the isotherm plateau can be attributed to the
      denser positive charge on the adsorbing polycation and that the ultimate coverage
      obtained corresponds to the adsorption of one oligomer onto each original
      negative silica charge, when the silica charge is most sparse, at pH 6. This
      limiting behavior breaks down at higher pHs where the greater silica charge
      density accommodates single chains adsorbing onto multiple negative sites. As a
      result of the greater substrate charge density and reduced polycation charge at
      higher pHs, the extent of charge overcompensation diminishes while the coverage
      increases on the plateau of the isotherm. Ultimately at the highest pHs, a regime
      is approached where the coil's excluded surface area, not surface charge, limits
      the ultimate coverage. In addition to quantifying the crossover from the charge
      limiting to the area-limiting behaviors, this paper quantitatively reports
      adsorption-induced changes in bound counterion density and ionization at the
      interface, which were generally found to be independent of coverage for this
      model system.

PMID- 16290460
TI  - Comparison of interfacial properties of electrodeposited single carbon
      fiber/epoxy composites using tensile and compressive fragmentation tests and
      acoustic emission.
AB  - Interfacial and microfailure properties of carbon fiber/epoxy composites were
      evaluated using both tensile fragmentation and compressive Broutman tests with an
      aid of acoustic emission (AE). A monomeric and two polymeric coupling agents were
      applied via the electrodeposition (ED) and the dipping applications. A monomeric
      and a polymeric coupling agent showed significant and comparable improvements in
      interfacial shear strength (IFSS) compared to the untreated case under both
      tensile and compressive tests. Typical microfailure modes including cone-shaped
      fiber break, matrix cracking, and partial interlayer failure were observed under
      tension, whereas the diagonal slipped failure at both ends of the fractured fiber
      exhibited under compression. Adsorption and shear displacement mechanisms at the
      interface were described in terms of electrical attraction and primary and
      secondary bonding forces. For both the untreated and the treated cases AE
      distributions were separated well in tension, whereas AE distributions were
      rather closely overlapped in compression. It might be because of the difference
      in molecular failure energies and failure mechanisms between tension and
      compression. The maximum AE voltage for the waveform of either carbon or large
      diameter basalt fiber breakages in tension exhibited much larger than that in
      compression. AE could provide more likely the quantitative information on the
      interfacial adhesion and microfailure.

PMID- 16290461
TI  - Preparation and characterization of dealuminated metakaolin and its use in the
      transformation of waste plastics to aromatic hydrocarbons.
AB  - Acid activated metakaolins (AAMKs) have been prepared by calcination of the
      natural clay at 600 degrees C to provide a metakolin which was then leached at 80
      degrees C for 3 h using 1M, 2M, 3M, and 6M HCl. These materials were
      characterized and their ability to transform the off gases from HDPE
      decomposition into useful aromatic species was evaluated. The amount of adsorbed
      water and the number of acid sites increased with the severity of acid treatment.
      Variable temperature DRIFTS spectroscopy of pyridine treated samples revealed
      that both Bronsted and Lewis acid centers were present until 425 degrees C.
      Pyridine bonded to the Lewis acid centers was more thermally stable. The AAMKs
      were all selective to the production of toluene with respectable, but lesser,
      amounts of xylenes and trimethylbenzenes. This selectivity contrasts with that of
      acid leached and pillared smectites which are selective toward trimethylbenzene.

PMID- 16290462
TI  - Precipitation of inorganic salts inside hollow micrometer-sized polyelectrolyte
      shells.
AB  - Hollow polymer shells formed by layer-by-layer adsorption of oppositely charged
      polyelectrolytes onto micrometer-sized colloidal particles with subsequent
      decomposition of the colloidal core were employed as a model system for the study
      of inorganic crystallization reactions in restricted volumes. The size-selective
      permeability of shells is used for spatially controlling the precipitation of
      inorganic salts CaCO3 and BaCO3 into the shell interior. Outside the shells the
      precipitation was suppressed by the polymers, which are unable to penetrate the
      shell wall. The precipitates were studied by scanning electron microscopy and
      atomic force microscopy. The fundamental and applied aspects of research on
      spatially confined synthesis of inorganic particles are under discussion.

PMID- 16290463
TI  - Effective spring description of a bubble or a droplet interacting with a
      particle.
AB  - It is shown that the interaction of a particle with a liquid drop or a gas bubble
      may be quantitatively described over the whole distance regime by treating the
      fluid interface as a Hookean spring. An algorithm suitable for analyzing atomic
      force microscopy data suitable for a calculator or a spread-sheet is given and
      applied to data for oil drops.

PMID- 16290464
TI  - Intraparticle surface diffusion of metal contaminants and their attenuation in
      microporous amorphous Al, Fe, and Mn oxides.
AB  - Intraparticle surface diffusion is an important and rate-limiting process in the
      sorption of metal ions to microporous sorbents such as those of hydrous amorphous
      Al (HAO), Fe (HFO), and Mn (HMO) oxides; these minerals are abundant in the
      environment, exhibiting a high affinity for metal contaminants. In aquatic
      systems representative of natural environments, internal micropore surfaces of
      HAO, HFO, and HMO can account for 40 to 90% of the sorption sites. Surface
      diffusivities have been observed to range between 10(-16) and 10(-10) cm2 s(-1)
      for metals including Sr, Cd, Zn, and Ni. The combination of significant
      microporosity and small diffusivities results in the amorphous oxides acting as
      natural attenuating sinks.

PMID- 16290465
TI  - Surface adsorption effects in the inkjet printing of an aqueous polymer solution
      on a porous oxide ceramic substrate.
AB  - The inkjet printing of a polymeric solution into a porous substrate was studied,
      with the focus on phenomena occurring within the pore space during infiltration.
      Lines of aqueous polyacrylic acid (PAA) solution were printed onto the surface of
      porous, high-green-density ceramic powder beds. The PAA is a binder for the
      ceramic particles, allowing removal of the printed line structure ("primitive")
      and characterization of the extent of polymer penetration. Large differences in
      cross section of the retrieved printed structure were observed between ceramic
      systems and for different specific surface area powders. A mechanism for
      "filtration" of the polymer by adsorption onto the ceramic particle surfaces
      during infiltration was proposed. The adsorption of PAA onto Al2O3, SiO2, and
      TiO2 was characterized via adsorption isotherms, and the trend of primitive cross
      section with PAA adsorption was consistent with the filtration hypothesis, as was
      the variation with powder-specific surface area. These results can be generalized
      to other systems where a solution is inkjet printed onto a porous substrate
      (e.g., inks on plain paper, porous coated papers, etc.) Utilization of the
      adsorption effects may allow confinement of the solute molecules (e.g., colorant)
      to a small region near the substrate surface.

PMID- 16290466
TI  - Adsorption of oleic acid at sillimanite/water interface.
AB  - The interaction of oleic acid at sillimanite-water interface was studied by
      adsorption, FT-IR, and zeta potential measurements. The isoelectric point (IEP)
      of sillimanite obtained at pH 8.0 was found to shift in the presence of oleic
      acid. This shift in IEP was attributed to chemisorption of oleic acid on
      sillimanite. Adsorption experiments were conducted at pH 8.0, where the
      sillimanite surface is neutral. The adsorption isotherm exhibited a plateau
      around 5 micromol/m2 that correspond to a monolayer formation. Adsorption of
      oleic acid on sillimanite, alumina, and aluminum hydroxide was studied by FT-IR.
      Chemisorption of oleic acid on the above substrates was confirmed by FT-IR
      studies. Hydroxylation of mineral surface was found to be essential for the
      adsorption of oleic acid molecules. These surface hydroxyl sites were observed to
      facilitate deprotonation of oleic acid and its subsequent adsorption. Thus
      protons from oleic acid react with surface hydroxyl groups and form water
      molecules. Based on the experimental results, the mechanism of oleic acid
      adsorption on mineral substrate was proposed. Free energy of adsorption was
      estimated using the Stern-Graham equation for a sillimanite-oleate system.

PMID- 16290468
TI  - Adsorption of n-alkanes on plasma-oxidized high-strength carbon fibers.
AB  - The objective of this work was to characterize the degree of heterogeneity
      brought about by oxygen plasma treatment of carbon fibers by studying its effects
      on the adsorption of n-alkanes. Untreated and unsized high-strength carbon fibers
      were subjected to oxygen plasma treatments with different degrees of severity. A
      sample of the same material oxidized following a standard industrial method was
      also studied for comparison. Adsorption of C5-C10n-alkanes at 303-353 K was
      measured by inverse gas chromatography (IGC). Elution peaks were symmetrical for
      the fresh and industrially oxidized samples; however, a large extent of asymmetry
      was observed for the plasma-treated fibers. Differences in surface heterogeneity
      were quantified in terms of several adsorption thermodynamic magnitudes.
      Differential heats of adsorption exhibited values similar to those corresponding
      to the probe-basal plane interaction. The dispersive component of the surface
      tension of the solids increased clearly upon plasma oxidation, the increase being
      systematic according to the severity of plasma treatment. It can be concluded
      that plasma oxidation generates high-surface-energy sites responsible for
      trapping of n-alkane molecules, this effect being more marked as the chain length
      increases. The possibility of this effect being associated to creation of
      micropores was ruled out on the basis of volumetric CO2 adsorption experiments
      and IGC measurements at finite dilution. Scanning tunneling microscopy
      observations allowed us to establish a possible connection between fiber surface
      nanostructure and IGC results. The sites accessible to n-alkane molecules in the
      industrially oxidized sample seem to be highly disordered, thus leading to a
      weaker interaction with the adsorbate.

PMID- 16290467
TI  - The sorption of anthracene onto goethite and kaolinite in the presence of some
      benzene carboxylic acids.
AB  - The uptake of anthracene from dilute aqueous solutions onto goethite and
      kaolinite was investigated at 25 degrees C, first in the absence and then in the
      presence of three benzene carboxylic acids: phthalic acid (benzene-1,2
      dicarboxylic acid), trimesic acid (-1,3,5-), and mellitic acid (-1,2,3,4,5,6-).
      Carboxylic acid concentrations were 0.20, 0.10, and 0.05 mM. Anthracene (0.20
      microM) did not adsorb strongly onto the pure mineral surfaces, but in the
      presence of phthalic acid a substantial increase in anthracene uptake was
      observed, particularly for the goethite systems. Trimesic and mellitic acids did
      not enhance anthracene uptake. Phthalate and proton adsorption data have been
      used to model phthalate adsorption onto the mineral surfaces using an extended
      constant capacitance surface complexation model. This model was then successfully
      adapted to account for the observed increase in anthracene uptake, where
      anthracene molecules were assumed to interact with adsorbed phthalate. We propose
      that the enhancement of anthracene adsorption in the presence of phthalic acid is
      due to an increase in the hydrophobicity of the mineral surface once phthalic
      acid molecules adsorb. The same effect was not observed for the other benzene
      carboxylates because of their greater polarity.

PMID- 16290469
TI  - Particulate hematite diffusion in sodium polyacrylate solutions. The effect of
      ionic strength.
AB  - The diffusion coefficients of hematite particles in polyelectrolyte solution have
      been investigated using dynamic light scattering. Two apparent diffusion
      coefficients, a fast and a slow diffusional mode, are observed for the hematite
      particles in high-molecular-weight sodium polyacrylate solution at pH 10.5. The
      slow diffusion coefficient (Dslow) shows a decrease with increase in
      polyelectrolyte concentration. The fast diffusion coefficient (Dfast) shows an
      increase to a maximum with increasing polyelectrolyte concentration and then a
      rapid decrease as the polyelectrolyte concentration increases further. With an
      increase in ionic strength from 10(-4) to 0.1 M NaNO3, the maximum value of Dfast
      increased in magnitude, while the polyacrylate concentration at which the maximum
      occurs is seen to increase. The dependence of Dfast on the measurement angle
      indicates that it is coupled to the fluctuations of the chains. The observed
      behavior is attributed to the hematite probe particle sensing both macroscopic
      (viscous) and elastic fluctuations associated with the polyelectrolyte motion.

PMID- 16290470
TI  - Forces between a rigid probe particle and a liquid interface. II. The general
      case.
AB  - The semianalytic theory developed previously (Chan, D. Y. C., Dagastine, R. R.,
      and White, L. R., J. Colloid Interface Sci. 236, 141 (2001)) to predict the force
      curve of an AFM measurement at a liquid interface using a colloidal probe has
      been expanded to incorporate a general force law with both attractive and
      repulsive forces. Expressions for the gradient of the force curve are developed
      to calculate the point at which the probe particle on the cantilever will
      spontaneously jump in toward the liquid interface. The calculation of the jump
      instability is reduced to a straightforward embroidery of the simple algorithms
      presented in Chan et al. In a variety of sample calculations using force laws
      including van der Waals, electrostatic, and hydrophobic forces for both oil/water
      and bubble/water interfaces, we have duplicated the general behaviors observed in
      several AFM investigations at liquid interfaces. The behavior of the drop as a
      Hookean spring and the numerical difficulties of a full numerical calculation of
      F(deltaX) are also discussed.

PMID- 16290471
TI  - Additional attraction between surfactant-coated surfaces.
AB  - A simple model that shows an additional attraction between solvated surfactant
      coated systems is developed. The model simply calculates the van der Waals
      attraction between the solvated surfactant layers. This attraction was previously
      neglected as it was expected to have a small energetic contribution. This is
      indeed the case; however, despite the small energetic contribution the force is
      large. In other words, although the expression that we get is small in energy, it
      is large in force. This is particularly important for surface force balance
      measurements, where using the developed expression, some apparent discrepancies
      between measured and theoretical values may now have a possible explanation, and
      especially those associated with surfactant-coated surfaces. We apply the new
      expression to a given system, and compare with the experimental results.

PMID- 16290472
TI  - Prediction and measurement of the interparticle depletion interaction next to a
      flat wall.
AB  - A theoretical and experimental study was performed to investigate the depletion
      interaction between two colloidal particles next to a solid wall in a solution of
      nonadsorbing macromolecules. By calculating the change in free volume available
      to the macromolecules upon approach of the two particles, a relatively simple
      expression was developed for the interparticle depletion attraction in hard
      sphere systems as a function of the particle-particle and particle-plate spacing.
      Perhaps the most useful result obtained from this analysis was that the wall has
      no effect whenever the ratio of the particle radius to the macromolecule radius
      is greater than four. (In charged systems, this ratio would apply to the
      effective particle and macromolecule sizes.) A series of experiments was then
      performed in which the hydrodynamic force balance (HFB) apparatus was used to
      measure the shear force needed to separate a colloidal doublet consisting of two
      particles trapped in a secondary energy well formed by a repulsive electrostatic
      force and an attractive depletion force. The macromolecules used here were small,
      nanometer-sized spheres of either silica or polystyrene. Agreement between the
      measured separation forces and those predicted using the force balance model of
      J. Y. Walz and A. Sharma (J. Colloid Interface Sci. 168, 485 (1994)) was within a
      factor of 1.3 using no adjustable parameters and accounting for polydispersity
      and uncertainty in the macromolecule size. It is shown that this remaining
      discrepancy could be caused by the Brownian (stochastic) nature of the doublet
      breakup process.

PMID- 16290474
TI  - Langmuir monolayers and the transferred films of fluorinated amphiphiles
      containing vinyl groups.
AB  - The monolayer behavior of long-chain esters of acrylic and methacrylic acids
      containing perfluoro or partially fluorinated carbon chains at the air/water
      interface was studied by surface pressure-area isotherm measurements and Brewster
      angle microscopy. It has been found that a minor change in the chemical
      structures of these fluorinated amphiphiles, such as a hydrogen substituted at
      the omega-position of the hydrophobic fluorocarbon tails instead of a fluorine as
      well as hydrophilic vinyl ester groups inserted between acrylates and
      methacrylates, induces a drastic change in the isotherms for the monolayers,
      suggesting different molecular orientation and packing in the films. The
      monolayers were transferred by horizontal lifting, Langmuir-Blodgett, and surface
      lowering methods to give the X-, Y-, and Z-type films, respectively. These films
      were characterized by scanning probe microscopy, to clarify the mesoscopic
      surface structures of the molecular films exposed with the hydrophilic or
      hydrophobic moieties in air, depending upon the dipping methods. The Z-type films
      with the outermost surface of the fluorinated substituents were examined in
      relation to the frictional properties that strongly depend upon the fluorine and
      the hydrogen atoms at the end of the hydrophobic fluorocarbon chains, which is
      controllable at the atomic level.

PMID- 16290473
TI  - A quartz crystal microbalance study of the adsorption of asphaltenes and resins
      onto a hydrophilic surface.
AB  - The adsorption of extracted and purified samples of asphaltenes and resins onto
      gold surfaces has been studied as a function of bulk concentration using a quartz
      crystal microbalance with dissipation measurements (QCM-D). With this device,
      which works equally well in transparent, opaque, and nontransparent samples, the
      adsorbed amount is measured through a change in resonant frequency of the quartz
      oscillator. The measured change in dissipation reports on changes in layer
      viscoelasticity and slip of the solvent at the surface. The results show that the
      adsorbed amount for resins from heptane corresponds to a rigidly attached
      monolayer. The adsorbed amount decreases with increasing amount of toluene in the
      solvent and is virtually zero in pure toluene. Asphaltenes, on the other hand,
      adsorb in large quantities and the mass and dissipation data demonstrate the
      presence of aggregates on the surface. The aggregates are firmly attached and
      cannot be removed by addition of resins. On the other hand, resins and
      asphaltenes associate in bulk liquid and the adsorption from mixtures containing
      both resins and asphaltenes is markedly different from that obtained from the
      pure components. Hence, we conclude that preformed resin aggregates adsorb to the
      surface. These results are compared and discussed in relation to adsorption from
      crude oil diluted in heptane/toluene mixtures.

PMID- 16290475
TI  - Fabrication of a covalently attached self-assembly multilayer film based on CdTe
      nanoparticles.
AB  - A precursor film has been fabricated from TGA (thiolglycolic acid)-stabilized
      CdTe nanoparticles and NDR (nitro-containing diazoresin) using electrostatic
      interactions and the standard layer-by-layer assembly method; covalent bonds are
      formed under ultraviolet irradiation. XPS provided evidence for the presence of
      CdTe nanoparticles within the polymer ultrathin films. UV-visible spectroscopy
      and FTIR spectroscopy provide evidence for the formation of a covalent linkage.
      Moreover, the UV-visible spectroscopy and AFM measurement support the improvement
      of the stability of the hybrid organic/inorganic film toward polar solvents when
      the linkages between the nanoparticles and polymer changed from ionic bonds to
      covalent bonds.

PMID- 16290476
TI  - Metallomicellar catalysis: catalytic cleavage of p-nitrophenyl picolinate by Cu2+
      complex of 4-chloride-2,6-bis(N-hydroxyethylaminomethyl)-benzophenol in micellar
      solution.
AB  - The hydrolysis of p-nitrophenyl picolinate (PNPP) catalyzed by the Cu(II) complex
      of 4-chloride-2,6-bis(N-hydroxyethylaminomethyl)-benzophenol was investigated
      kinetically by observing the rates of release of p-nitrophenol in the presence of
      three surfactants, which are hexadecyltrimethylammonium bromide, n
      lauroylsarcosine sodium, and polyoxyethylene23 lauryl ether, at different pH and
      25 degrees C. The scheme for the reaction involving a ternary complex comprising
      ligand, metal ion, and substrate in a micelle was established, and the relative
      kinetic and thermodynamic parameters were determined, including first-order rate
      constant (kN), association constant (Ks) for ternary complex, and pKa for the
      hydroxide ion of the ternary complex. The reaction mechanism was discussed.

PMID- 16290477
TI  - Sliding of liquid drops down an inclined solid surface.
AB  - A liquid drop that partially wets a solid surface will slide down the plane when
      it is tilted beyond a critical inclination. Here we report the study of the
      sliding velocity of such a drop. Experiments for measuring the steady sliding
      velocity of different liquids of drops are performed. We then construct a scaling
      law that predicts the sliding velocity given the physical properties, wetting
      characteristics, and size of the drop. When the sliding velocity is low and the
      drop distortion due to inclination is small, the scaling law is shown to
      correctly model the functional dependency of the measured sliding velocity.

PMID- 16290478
TI  - Influence of counterion on the interaction of dodecyl sulfates and cellulose
      ethers.
AB  - Fluorescence probe techniques together with microcalorimetry and dye
      solubilization were used to study the interaction between nonionic polymers and
      anionic surfactants with different monovalent counterions in order to examine the
      effects of the counterion. The polymers used were the cellulose ethers
      hydroxypropyl methyl cellulose (HPMC) and ethyl hydroxyethyl cellulose (EHEC).
      The surfactants were dodecyl sulfates with potassium, sodium, and lithium as
      counterions (KDS, NaDS, LiDS). The counterion influenced the interaction start
      concentration as well as the nature of the mixed aggregates formed. The
      interaction start, according to surfactant concentration, was found to be in the
      order KDS < NaDS < LiDS for both polymers as well as in aqueous solution. From
      fluorescence measurements it was found that the KDS-polymer aggregates shield
      pyrene from water better than the other surfactants, indicating larger aggregates
      with a more fluid interior. The microcalorimetry measurements confirm that the
      adsorption of the surfactants onto the polymer is endothermic and entropy driven
      at the start and as more clusters are formed on the polymer chains the process
      converts to being exothermic and driven by both enthalpy and entropy.

PMID- 16290479
TI  - A study of identifying the emulsion type of surfactant: volume balance value.
AB  - A new method for identifying the emulsion type of surfactant is introduced-
      volume balance value, that is, the ratio of hydrophilic group and hydrophobic
      group volumes in surfactant. The radius used in the volume for the VB value comes
      from the Pauling radius based on quantum chemistry. The result shows that the
      surfactant is an o/w emulsifying agent and water-soluble when the VB is more than
      1, and is a w/o emulsifying agent and oil-soluble when the VB is less than 1. The
      VB value possesses additivity.

PMID- 16290480
TI  - Comparison of the coadsorption of benzyl alcohol and phenyl ethanol with the
      cationic surfactant, hexadecyl trimethyl ammonium bromide, at the air-water
      interface.
AB  - A comparison of the coadsorption of benzyl alcohol and phenyl ethanol with the
      cationic surfactant, hexadecyl trimethyl ammonium bromide, C16TAB, at the air
      water interface is made using the specular reflection of neutrons. The phenyl
      ethanol is more surface active than the benzyl alcohol, and competes more
      effectively with the C16TAB for the interface. The structure of the C16TAB
      component in the mixed monolayer is compared with the structure of the pure
      C16TAB monolayer at an equivalent area per molecule. The addition of the aromatic
      alcohol subtly alters the conformation of the C16TAB and draws it closer to the
      aqueous subphase. The center of the alcohol distribution is located in the
      interface adjacent to the C6 group of the C16TAB alkyl chain closest to the
      headgroup. Compared to the benzyl alcohol, the more hydrophobic phenyl ethanol is
      slightly farther away from the headgroup, and has a greater impact on the
      conformation of the alkyl chain of the C16TAB.

PMID- 16290481
TI  - Adsorption of nonionic mixtures at the air-water interface: effects of
      temperature and electrolyte.
AB  - Specular neutron reflection has been used to investigate the effects of
      temperature and added electrolyte on the adsorption of nonionic surfactants and
      nonionic surfactant mixtures at the air-water interface. For the alkyl poly
      oxyethylene oxide nonionic surfactants, C(n)EO(m), the adsorption at the air
      water interface is independent of temperature for surfactants with shorter
      ethylene oxide groups, whereas there is an increasing tendency for increased
      adsorption with temperature for surfactants with longer ethylene oxide groups.
      The addition of "salting in" (sodium thiocyanate, NaSCN) and "salting out"
      (sodium chloride, NaCl, sodium sulphate, Na2SO4) electrolyte results in reduced
      and enhanced adsorption, respectively, for C12EO8, whereas both types of
      electrolyte result in enhanced adsorption for C12EO12. The addition of
      electrolyte does not substantially alter the temperature dependence of the
      adsorption of the pure monolayers. For the nonionic mixtures of C12EO3/C12EO8
      increasing temperature results in a surface richer in the least surface-active
      component, C12EO8. For the same nonionic mixture, the addition of "salting in"
      and "salting out" electrolyte results in an reduced and increased adsorption,
      respectively. The addition of "salting in" electrolyte results in a surface more
      rich in C12EO3, whereas for the addition of both "salting in" and "salting out"
      electrolyte the surface composition is essentially unaltered.

PMID- 16290482
TI  - Correlation between transient shear experiments and structure evolution of
      aqueous foams.
AB  - This experimental work deals with rheological properties of aqueous foams and
      slip phenomena. Rheological measurements are performed on a stable foam with a
      parallel plate rheometer. When a constant shear rate is applied to foam, two
      regimes can be identified in the recorded stress vs time curve: a transient
      regime where the structure evolves and where the recorded stress varies, followed
      by a steady state regime where the stress is stabilized. Measurements, modeling,
      and elimination of the slip velocity are performed. Experiments with grooved
      surfaces allow elimination of slip at the wall. From measurements at two gaps
      with smooth surfaces, we use two slip correction methods and check their validity
      by a direct comparison with actual measurements (with grooved surfaces). A foam
      rheological equation can be determined from the measurements. Finally, using an
      optical device coupled with image analysis software, foam texture is investigated
      on the basis of its evolution with shear rate and time. Evolution of the bubbles
      size and arrangement into the gap with time of shearing are shown. The transient
      regime is identified as a regime where the intimate structure of the foam
      evolves. Slip velocity is also evidenced and measured with the visualization
      device.

PMID- 16290483
TI  - Enzymatically prepared n-alkyl esters of glucuronic acid: the effect of
      hydrophobic chain length on surface properties.
AB  - The effect of hydrophobic chain length on surface properties of enzymatically
      prepared n-alkyl esters of glucuronic acid are examined. Dynamic parameters from
      Hua and Rosen's mathematical model and equilibrium surface tension are presented
      for esters with octyl, decyl, dodecyl, and tetradecyl alkyl segments. Increasing
      the alkyl chain length has a significant influence on the surface activity. Decyl
      and dodecyl glucuronate exhibit an interesting adsorption speed associated with
      foaming capacity. Octyl glucuronate exhibits a micellar organization as its bulk
      concentration is over 10.68 mM.

PMID- 16290484
TI  - Effect of ethanol on micellization and on decarboxylation of 6-nitrobenzisoxazole
      3-carboxylate in aqueous cationic micelles.
AB  - The effects of ethanol on the critical micellar concentration (cmc) and the rates
      of decarboxylation of 6-nitrobenzisoxazole-3-carboxylate (6-NBIC) have been
      investigated in aqueous cationic surfactants of the cetyltrialkylammonium family
      with bromide [CT(R)ABr], chloride [CT(R)ACl], and nitrate [CT(R)ANO3]
      counterions, and methyl (CTAX), n-propyl (CTPAX), and n-butyl (CTBAX) as the head
      group alkyl moieties. Effects upon cmc and reactivity are similar, featuring a
      break at the ethanol mole fraction, x(EtOH), of ca. 0.055; these effects have
      been related to changes in solvent structure, with formation of a clathrate at
      x(EtOH) = 0.055. Rate data in CTBABr were further investigated and fitting of raw
      kinetic data to the pseudophase model is possible up to x(EtOH) = 0.1, showing an
      unexpected decrease of rate constant values in the micellar pseudophase, kM', as
      ethanol content increases: a significant variation of micellar ionization degree
      could account for this kinetic effect.

PMID- 16290485
TI  - Effect of water-soluble polymers on the morphology of aerosol OT vesicles.
AB  - Vesicles of different morphologies were found to form in aqueous solutions of the
      surfactant sodium bis(2-ethylhexyl)sulfosuccinate, AOT, and in binary mixtures
      composed of AOT with poly(ethylene glycol) and poly(sodium 4-styrenesulfonate).
      Using electrical conductivity and fluorescence probing, two critical vesicle
      concentrations, cvc and cac, were determined. These critical aggregation
      concentrations correspond to different kinds of aggregates, which are easily
      observed by optical microscopy.

PMID- 16290486
TI  - Adsorption properties of novel gemini surfactants with nonidentical head groups.
AB  - Novel environmentally friendly gemini surfactants, each with two hydrophilic and
      two hydrophobic groups, have been synthesized and their physicochemical
      properties investigated. One of the hydrophilic groups is a methyl-capped
      polyoxyethylene chain with mol wt 350, 550, and 750 g/mol, respectively, and the
      other is a sulfate group; the hydrophobic part of the surfactant is made from
      oleylnitrile. This nitrile derivative of the fatty acid is used to achieve good
      hydrolytic stability. Du Nouy ring and maximum bubble pressure tensiometry were
      used for equilibrium and dynamic surface tensions, gamma(e) and gamma(t),
      respectively. The aqueous-phase critical micelle concentrations of the
      heterogeminis (HGs) have been investigated. The results have been compared with
      those for mixtures of standard surfactants sodium decylsulfate and
      octaoxyethyleneglycol mono n-decyl ether under equivalent conditions. The HGs are
      shown to exhibit improved performance over the mixed system both in terms of
      micellization and surface tension lowering. Dynamic surface tension (DST) studies
      were performed to investigate air-water adsorption mechanisms. A diffusion
      limited mechanism was confirmed in the initial stages of adsorption. However,
      closer to the equilibrium the DST data are inconsistent with a diffusion-only
      mechanism. In particular, the HGs show a larger deviation from diffusion control
      as compared to the model mixture, which is a signature of slower adsorption
      kinetics. In addition to air-water interfaces, properties of these HGs have also
      been investigated at solid silica-solution surfaces by optical reflectometry.
      These surfaces were either naturally hydrophilic or rendered hydrophobic by
      chemical modification. On either surface the maximum amount of adsorbed
      surfactant was found to increase when the polyoxyethylene chain length decreases.

PMID- 16290487
TI  - Studies of the aggregation behavior of cyclic gemini surfactants.
AB  - The specific conductance, surface tension, mean aggregation number, and apparent
      molar volume properties of aqueous solutions of a novel series of N,N'
      bis(cyclododecyldimethyl)-alpha,omega-alkanediammonium dibromide (c12-s-c12)
      surfactants, where s is the spacer chain length, are reported. Surfactants with s
      = 3, 4, and 6 have been prepared and characterized in terms of their Krafft
      temperature (T(Kr)), critical micelle concentration (cmc), surfactant head group
      area (a) at the air-water interface, mean aggregation number (N(agg)), and the
      volume change upon micelle formation (deltaV(phi,M)). The c12-3-c12 shows little
      evidence of aggregate formation, while the results obtained for the c12-4-c12 and
      c12-6-c12 homologues suggest the formation of small, poorly defined micellar
      aggregates in aqueous solution.

PMID- 16290488
TI  - Mesoscopic dispersion of colloidal agglomerate in a complex fluid modelled by a
      hybrid fluid-particle model.
AB  - The dispersion of the agglomerating fluid process involving colloids has been
      investigated at the mesoscale level by a discrete particle approach--the hybrid
      fluid-particle model (FPM). Dynamical processes occurring in the granulation of
      colloidal agglomerate in solvents are severely influenced by coupling between the
      dispersed microstructures and the global flow. On the mesoscale this coupling is
      further exacerbated by thermal fluctuations, particle-particle interactions
      between colloidal beds, and hydrodynamic interactions between colloidal beds and
      the solvent. Using the method of FPM, we have tackled the problem of dispersion
      of a colloidal slab being accelerated in a long box filled with a fluid. Our
      results show that the average size of the agglomerated fragments decreases with
      increasing shearing rate gamma, according to the power law A x gamma(k), where k
      is around 2. For larger values of gamma, the mean size of the agglomerate S(avg)
      increases slowly with gamma from the collisions between the aggregates and the
      longitudinal stretching induced by the flow. The proportionality constant A
      increases exponentially with the scaling factor of the attractive forces acting
      between the colloidal particles. The value of A shows a rather weak dependence on
      the solvent viscosity. But A increases proportionally with the scaling factor of
      the colloid-solvent dissipative interactions. Similar type of dependence can be
      found for the mixing induced by Rayleigh-Taylor instabilities involving the
      colloidal agglomerate and the solvent. Three types of fragmentation structures
      can be identified, which are called rupture, erosion, and shatter. They generate
      very complex structures with multiresolution character. The aggregation of
      colloidal beds is formed by the collisions between aggregates, which are
      influenced by the flow or by the cohesive forces for small dispersion energies.
      These results may be applied to enhance our understanding concerning the
      nonlinear complex interaction occurring in mesoscopic flows such as blood flow in
      small vessels.

PMID- 16290489
TI  - Pore-scale study of nonaqueous phase liquid dissolution in porous media using
      laser-induced fluorescence.
AB  - Little quantitative, experimental pore-scale information exists regarding
      nonaqueous phase liquid (NAPL) ganglia undergoing dissolution in porous media. By
      using refractive index matched fluids and porous media, we have been able to
      nonintrusively visualize NAPL dissolution (at constant capillary numbers) in
      three dimensions using laser-induced fluorescence. The results provide dynamic,
      quantitative information regarding ganglia surface area, volume, position, and
      shape. It appears that ganglia smaller than a few pore volumes are spheroid,
      whereas larger ganglia exhibit a fractal area to volume scaling. Evidence of
      ganglia breakup is found for all capillary numbers studied. Mobilization,
      however, is only important at higher capillary numbers.

PMID- 16290490
TI  - Comparison of surface properties of random, block, and graft copolymers having
      perfluoroalkyl and silicone-containing side chains.
AB  - Fluorosilicone copolymers of random, block, and graft with both perfluoroalkyl
      and silicone-containing side chains were synthesized, and their surface
      properties and surface modification effects on PVC film were compared. It can be
      confirmed that the fluorosilicone copolymers of random, block, and graft exhibit
      very low surface free energies of 9-13 dyn/cm, depending on the perfluoroalkyl
      group content and their molecular structure. The inherent surface free energies
      of the fluorosilicone copolymers are significantly influenced by their molecular
      structure and perfluoroalkyl group content. It can also be found that the
      fluorosilicone copolymers are very effective for lowering surface free energy.
      The surface free energy of a copolymer/PVC blend strongly varies with
      perfluoroalkyl group content as well as molecular structure. The molecular
      structure of a fluorosilicone copolymer is as important as the perfluoroalkyl
      group content for their inherent surface free energies and surface modification
      of other polymers.

PMID- 16290492
TI  - Adsorption of Cd(II) ion and its complex compounds from solution on the surface
      of charcoal treated with an oxidation-negative ionizing method.
AB  - The adsorption characteristics of Cd(II) from electrolytic solution by activated
      charcoal have been investigated. It was found that the amount of adsorption of
      Cd(II) depends mainly on the pH value of the solution, the number of added
      inorganic ions, and oxygen-containing groups on the surface. The activated
      charcoal was treated with the oxidation-negative ionizing (OA) method to produce
      more oxygen-containing groups on the surface. The adsorption amount of Cd(II) on
      the treated activated charcoal increased remarkably. It was also found that the
      more powerful the acidity of the surface and the larger the adsorption amount of
      Cd(II), so the charged groups on the surface of activated charcoal are considered
      as the main adsorption-activated sites for inorganic ions. The adsorption
      characteristics of various complexes of Cd(II) on the surface of activated
      charcoal have also been investigated. Three types of adsorption configuration of
      the complexes of Cd(II) on the surface of activated charcoal were suggested
      according to the experimental results.

PMID- 16290491
TI  - Aggregation and decomposition of a pseudoisocyanine dye in dispersions of layered
      silicates.
AB  - The optical properties of reaction systems composed from a pseudoisocyanine (PIC)
      solution and dispersed layered silicates were studied using visible spectroscopy.
      Two series of reduced-charge montmorillonites were used as the silicate
      materials. Each series consisted of eight samples with different layer charges,
      which were prepared from one parent material. Observed trends were verified with
      another series of dioctahedral and trioctahedral smectites of different layer
      charges, structure, and origin. The layer charge density of the silicates
      significantly affected the aggregation of PIC cations. In addition to the
      formation of J-aggregates, dye spectral bleaching was also observed. Silicates
      with very low charge densities induced neither significant aggregation nor
      spectral bleaching of the dye. The highest levels of PIC J-aggregate formation
      were found in dispersions of the layered silicates with a medium surface charge.
      However, reversible spectral bleaching was also observed in some cases. PIC dye
      cations probably change their conformations during the adsorption process, due to
      the tension resulting from the large size of the cations and the relatively high
      charge density at the silicate surface. The bleached dye recovers, at least
      partially, with the rearrangement and redistribution of the dye cations over the
      time. In contrast, the presence of silicates with very high charge densities
      (synthetic taeniolite and fluorohectorite) led to the very fast and irreversible
      decomposition of the PIC. Perhaps, the tension in adsorbed dye cations, induced
      by the high charge density at the silicate surface, resulted in significant
      destabilization and a decomposition reaction of the chromophore.

PMID- 16290493
TI  - Describing adsorption of paracetamol from aqueous solution on carbons while
      utilizing the most widespread isotherm models--the impact of surface carbonyl and
      basic groups.
AB  - The 15 most widespread adsorption isotherm equations are applied for describing
      recently published paracetamol adsorption data from aqueous solutions (pH 7).
      Twelve adsorption isotherms, measured at 300, 310, and 320 K, on the series of
      chemically modified carbons D43/1 (Carbo-Tech, Essen, Germany) differing in
      surface properties (from basic to strongly acidic) but possessing almost the same
      porosity, are analyzed. The results of fitting theoretical models to experimental
      data are arranged according to a decrease in the average value of the
      determination coefficient. From the models studied the best fit is obtained for
      Weber-Vliet, Dubinin-Astakhov, and the model published by Jossens. The most
      important conclusion is that at the lowest temperature studied, where the effect
      of carbon surface composition on adsorption properties is the most strongly
      marked, the value of paracetamol maximal adsorption decreases as the amount of
      surface basic groups and carbonyls increases.

PMID- 16290495
TI  - Preparation of microspheres by an emulsification-complexation method.
AB  - Microspheres were prepared by complexation of a cationic polymer, polyquaternium
      24, and an anionic surfactant, sodium lauryl sulfate (SLS). The cationic polymer
      solution was emulsified in dimethylsiloxane to give water in silicone emulsion
      (W/Si), and it was used as a template for the formation of microspheres. The
      emulsion was dispersed into the SLS solution. In this process, two kinds of
      droplets, silicone dropletes and microspheres composed of the cationic polymer
      and SLS, were formed, evidenced by X-ray energy dispersive spectra. The mean
      diameter of the microspheres was reduced from 105.7 to 64.8 mum as the stirring
      rate for W/Si preparation increased from 300 to 1000 rpm. It is believed that
      water droplets in W/Si emulsion, when exposed to SLS solution, could be
      solidified by the complexation of the cationic polymer and the anionic
      surfactant.

PMID- 16290496
TI  - Aspects on the interaction between sodium carboxymethylcellulose and calcium
      carbonate and the relationship to specific site adsorption.
AB  - The mechanisms of adsorption and association for sodium carboxymethylcellulose
      (NaCMC) in calcium carbonate suspensions have been determined from isothermal
      calorimetry and adsorption measurements. The equilibrium adsorption isotherms
      were determined by two different methods of separation; a depletion method and a
      serum exchange method. The enthalpy of dilution for NaCMC was determined on
      supernatants obtained from the calcium carbonate suspensions in order to
      investigate the interaction between NaCMC and dissolved species from the mineral.
      For comparison, NaCMC was injected into CaCl(2) solutions in order to determine
      the role of calcium ions in the adsorption process. The initial part of the
      adsorption isotherm showed a quasi-infinite slope indicating a high affinity for
      the NaCMC to the calcium carbonate surface, which was significantly reduced when
      anionic sodium polyacrylate was preadsorbed onto the calcium carbonate implying
      competitive adsorption. An endothermic enthalpy change was observed between the
      NaCMC and the calcium carbonate surface, suggesting attachment of the carboxylic
      acid groups onto the hydrated calcium sites. A similar endothermic enthalpy was
      observed when NaCMC was injected into CaCl(2) solutions or supernatants obtained
      from the calcium carbonate suspensions, indicating a complexation of carboxylic
      acid groups and hydrated calcium ions. It was concluded that the mechanisms of
      interaction of NaCMC in calcium carbonate suspensions are primarily an
      association between NaCMC and Lewis acid sites on the calcium carbonate surface
      and the formation of NaCMC-Ca(2+) complexes in the bulk solution, both of which
      will be affected by the amount of anionic sodium polyacrylate present.

PMID- 16290497
TI  - Free energy of interaction of sodium dodecyl sulfate in aqueous solution with
      carbon black surfaces.
AB  - The free energy of the adsorption process of an ionic surfactant from aqueous
      solutions onto a set of carbon blacks in the range of low concentrations was
      evaluated using the model proposed by van Oss and co-workers. The obtained
      results indicated that the free energy of interaction between adsorbent and
      adsorbate through water results mainly from Lifshitz-van der Waals and
      electrostatic interactions, and its value showed a good correspondence with that
      previously found from a combination of the classical measurements of adsorption
      isotherms and the Langmuir model.

PMID- 16290498
TI  - Adsorption of N-tallow 1,3-propanediamine-dioleate collector on albite and quartz
      minerals, and selective flotation of albite from greek stefania feldspar ore.
AB  - The adsorption behavior of tallow 1,3-propanediamine-dioleate (Duomeen TDO)
      collector on albite and quartz minerals is assessed through Hallimond flotation,
      zeta potential, and diffuse reflectance FTIR investigations, together with the
      species distribution of the collector. The collector performance on albite
      separation from a natural feldspar material is evaluated in bench scale flotation
      tests. The Hallimond flotation responses of the minerals as a function of pH and
      collector concentration indicate that albite can be selectively floated from
      quartz at pH 2 where the doubly positively charged collector species adsorb on
      albite but not on quartz. However, the zeta potential and infrared spectra reveal
      that the adsorption behavior of the collector is similar on both minerals. The
      discrepancy in the flotation and adsorption results is attributed to the coarse
      and fine particle size fractions, and the shorter and longer equilibration
      periods employed in these studies respectively. The comparable adsorption on fine
      particles of albite and quartz at pH 2 is explained by the interaction of
      ammonium ions on silanol groups by hydrogen bonding as well as electrostatic
      interactions. The changes in zeta potentials are in good agreement with the
      formation of ionic species and free molecular forms of the collector. The IR
      spectra show the coexistence of neutral oleic acid together with charged amine
      species at low pH values in accordance with the species distribution diagram.
      Selective flotation of albite is accomplished from a natural feldspar material
      with tallow diamine-dioleate collector at pH 2 using sulfuric acid, only when the
      feed is deslimed prior to the bench scale flotation tests. An albite recovery
      exceeding 85% is achieved from a feed material containing about 50% albite.

PMID- 16290499
TI  - The specific adsorption of sodium cations on less common metal oxides at high
      ionic strengths.
AB  - Sodium cations adsorb specifically on metal oxides at high ionic strengths. This
      results in a shift in the isoelectric point (IEP) to higher pH values. When the
      critical concentration of electrolyte is exceeded there is no IEP at all and the
      electrokinetic potential is positive even at very high pH values. The critical
      NaI concentration is rather insensitive to the nature of the metal oxide (but
      silica behaves differently), and this suggests that the specific adsorption is
      chiefly due to ion-ion and ion-solvent interaction in solution. The experimental
      results obtained with indium and niobium oxides (critical concentrations of about
      0.35 mol dm(-3)) confirmed this trend.

PMID- 16290500
TI  - Application of a single model to study the adsorption kinetics of prednisolone on
      six carbonaceous materials.
AB  - The knowledge of the adsorption processes of nonelectrolytes from liquid solution
      on solid materials involves the study of their kinetic and equilibrium aspects as
      well as the understanding of their thermodynamic functions. However, in most
      published papers adsorption isotherms are analyzed by using the Giles
      classification and other proposed equations which are either empirical or based
      on kinetic or thermodynamic criteria. Our opinion is that both the kinetic and
      the equilibrium studies must be complementary and that, in general, equations
      describing the adsorption isotherms come from the kinetic laws governing the
      different partial processes which determine the global process. These kinetic
      laws may be derived from single models. In this paper a single model is proposed,
      which makes it possible to establish a kinetic law satisfactorily fitting a great
      number of C (concentration) vs t (time) isotherms. This model has been applied to
      study the adsorption process of prednisolone by six carbonaceous materials from
      ethanol solution, the specific adsorption rate, and the activation thermodynamic
      functions being calculated. The results obtained have also been used to analyze
      the influence of the intraparticle diffusion on the kinetics of the process.

PMID- 16290501
TI  - Emulsifier-free emulsion polymerization produces highly charged, monodisperse
      particles for near infrared photonic crystals.
AB  - We have developed emulsifier-free, emulsion polymerization recipes for the
      synthesis of highly charged, monodisperse latex particles of diameters between
      500 and 1100 nm. These latexes consist of poly[styrene-(co-2-hydroxyethyl
      methacrylate)] spherical particles whose surfaces are functionalized with sulfate
      and carboxylic acid groups. These highly charged, monodisperse particles readily
      self-assemble into robust, three-dimensionally ordered crystalline colloidal
      array photonic crystals that Bragg diffract light in the near infrared spectral
      region. By altering the particle number density, the diffraction wavelength can
      be tuned from approximately 1000 to approximately 4000 nm.

PMID- 16290502
TI  - Emanation thermal analysis study of the preparation of ruthenia-titania-based
      finely dispersed powders.
AB  - Emanation thermal analysis (ETA), thermogravimetry (TG), differential thermal
      analysis (DTA), X-ray diffraction analysis (XRD), and transmission electron
      microscopy (TEM) were used for the characterization of thermal behavior of
      hydrous oxides (RuO(2))(x)-(TiO(2))(1-x).nH(2)O and dehydrated oxides (RuO(2))
      (x)-(TiO(2))(1-x), respectively (x=1, 0.9, and 0.7) on heating in argon and argon
      +10% hydrogen, respectively. The samples were heated in the range 20-600 degrees
      C at the constant heating rate 6 K/min. From the TG and DTA results the
      temperature intervals of dehydration and/or reduction of ruthenium dioxide into
      Ru metal were determined. ETA (based on the measurement of radon previously
      incorporated into the sample) brought about the information about surface area
      development and microstructure changes in the near surface layers up to 80 nm
      under in situ conditions of the heating. The temperature intervals of the
      annealing of near surface and structure defects serving as diffusion paths for
      radon were determined from the ETA results.

PMID- 16290503
TI  - Colloidal stability of a temperature-sensitive poly(N-isopropylacrylamide/2
      acrylamido-2-methylpropanesulphonic acid) microgel.
AB  - In this work, a study of the thermally induced flocculation of poly(N
      isopropylacrylamide/2-acrylamido-2-methylpropanesulphonic acid) microgel, that
      is, poly(NIPAM/aMPS) microgel samples is presented. The aggregation process is
      monitored in continuous by dynamic light scattering measurements. Theoretical
      explanations are considered and discussed in terms of interaction potentials,
      paying special attention to osmotic and elastic contributions due to particle
      interpenetration. The rate of aggregation is studied as a function of
      temperature, and theoretical calculations of kinetic constants based on model
      core-shell particle interactions provide very good agreement with experimental
      results. The reversibility of aggregation is also analyzed. It is found that
      aggregation is completely reversible only under certain conditions: the
      temperature of an aggregated sample must decrease under 20 degrees C. These
      results are experimental evidence of the secondary minimum in the interaction
      potential where aggregation occurs.

PMID- 16290504
TI  - Synthesis of microspheres stabilized sterically with two-component grafted chains
      by dispersion copolymerizations using mixture of two macromonomers in nonaqueous
      media.
AB  - The polymer microspheres were synthesized by dispersion copolymerization of
      divinylbenzene (DVB) with two vinylbenzyl-terminated poly(ethylene glycol
      methylether) (PEG)/poly(t-butyl methacrylate) (PBMA) macromonomer blends in
      methanol. In these systems of two macromonomer blends as the emulsifier, the
      polymer microspheres formed had a very narrow particle size distribution. Two
      macromonomers formed comicelles with DVB monomer and acted not only as the
      comonomer but also as the stabilizer. Such polymer microspheres were stabilized
      sterically with two-component grafted chains, such as PEG and PBMA, in methanol.

PMID- 16290505
TI  - Colloid particle adsorption at random site (heterogeneous) surfaces.
AB  - Irreversible adsorption of colloid particles and globular proteins at
      heterogeneous surfaces was studied theoretically. The substrate surface was
      created by covering a uniform surface by coupling sites (active centers) of a
      desired coverage. In contrast to previous studies concerned with disks, in our
      simulations the centers were modeled by spheres having a size smaller than that
      of the adsorbing particles. Adsorption was assumed to occur due to short-ranged
      attractive interactions if the colloid particle contacted the center. The Monte
      Carlo-type simulations enabled one to determine the initial flux, adsorption
      kinetics, jamming coverage, and the structure of the particle monolayer as a
      function of the site coverage and the particle/site size ratio, denoted by
      lambda. It was revealed that the initial flux increased significantly with the
      site coverage theta(s) and the lambda parameter. This behavior was quantitatively
      interpreted in terms of the scaled particle theory. It also was demonstrated that
      particle adsorption kinetics and the jamming coverage increased significantly, at
      fixed site coverage, when the lambda parameter increased. Practically, for
      alpha=lambda(2)theta(s)>1 the jamming coverage at the heterogeneous surfaces
      attained the value pertinent to continuous surfaces. The results obtained prove
      unequivocally that the spherically shaped sites are much more effective in
      binding particles than the disk-shaped sites considered previously.

PMID- 16290506
TI  - Diffusiophoresis in a suspension of spherical particles with arbitrary double
      layer thickness.
AB  - The diffusiophoresis in a homogeneous suspension of identical dielectric spheres
      with an arbitrary thickness of the electric double layers in a solution of a
      symmetrically charged electrolyte with a constant imposed concentration gradient
      is analytically studied. The effects of particle interactions (or particle volume
      fraction) are taken into account by employing a unit cell model, and the overlap
      of the double layers of adjacent particles is allowed. The electrokinetic
      equations that govern the ionic concentration distributions, the electrostatic
      potential profile, and the fluid flow field in the electrolyte solution
      surrounding the charged sphere in a unit cell are linearized assuming that the
      system is only slightly distorted from equilibrium. Using a perturbation method,
      these linearized equations are solved with the surface charge density (or zeta
      potential) of the particle as the small perturbation parameter. Analytical
      expressions for the diffusiophoretic velocity of the dielectric sphere in closed
      form correct to the second order of its surface charge density or zeta potential
      are obtained from a balance between its electrostatic and hydrodynamic forces.
      Comparisons of the results of the cell model with different conditions at the
      outer boundary of the cell are made.

PMID- 16290507
TI  - The electrical double layer on gold probed by electrokinetic and surface force
      measurements.
AB  - Gold surfaces, obtained by vacuum deposition of 15-nm gold films on glass and
      silica wafers, were studied in aqueous solutions by streaming potential
      measurements and colloidal-probe AFM force measurements. In the force
      measurements both a bare and a gold-coated silica particle (6 microm in diameter)
      have been used as colloidal probes. From the streaming potential measurements we
      determined the zeta-potential of the gold surface, while from the force
      measurements the diffuse double-layer potential psi(d) was obtained by fitting
      the data to the DLVO theory or to the nonlinear Poisson-Boltzmann equation.
      Measured interactions were found to be entirely due to overlap of electric double
      layers with no indication of attractive Van der Waals forces. Results of both
      types of measurements are in good agreement. The double layer potential strongly
      depends on the pH, probably as a result of the presence of oxide species on the
      gold surface. Insight in the double layer potential of polarizable interfaces
      such as the gold/electrolyte solution interface is the first step for
      understanding the effect of externally applied potentials on the adsorption
      behavior of charged species.

PMID- 16290508
TI  - Structural evolution of octyltriethoxysilane films on glass surfaces during
      annealing at elevated temperature.
AB  - Glass samples treated by octyltriethoxysilane were annealed for times ranging
      from 0 to 16 h, and their topography, adhesion, and stiffness properties were
      examined using pulsed-force mode (PFM) atomic force microscopy. While the
      surfaces of samples dried at room temperature were structurally featureless,
      those annealed at 145 degrees C showed formation of islands, increasing in size
      and number with heating time. PFM adhesion and stiffness maps suggested that the
      glass substrate remained at least partially covered by silanes even after island
      formation.

PMID- 16290509
TI  - Non-newtonian behavior of an insoluble monolayer: effects of inertia.
AB  - Interfacial velocity measurements were performed in an optical annular channel,
      consisting of stationary inner and outer cylinders, a floor rotating at a
      constant rate, and a flat free surface on which an insoluble monolayer was
      initially spread. Measurements for essentially inviscid monolayers and some
      viscous monolayers on water show good agreement with numerical predictions for a
      Newtonian interface (Boussinesq-Scriven surface model) coupled to a bulk flow
      described by the Navier-Stokes equations. Here, we consider in detail a viscous
      monolayer, namely hemicyanine, and find that above a certain concentration, the
      monolayer does not behave Newtonian at a Reynolds number of about 250. We show
      that the discrepancies between the measurements and predicted Newtonian behavior
      are not due to compositional effects (i.e., nonuniform monolayer distribution),
      Reynolds number (i.e., inertia and/or secondary flows), or surface dilatational
      viscosity (which does not play any role in the parameter regime investigated). We
      show prima facie evidence that the observed shear thinning nature of the velocity
      profile is associated with a phase transition at C approximately 0.9 mg/m(2) at
      low Reynolds numbers. At large Reynolds numbers (Re=8500), hemicyanine is found
      to flow like a viscous Newtonian monolayer on the air/water interface, with
      viscosity dependent only on the local concentration.

PMID- 16290510
TI  - Effect of crystallite size on the thermal phase change and porous properties of
      boehmite.
AB  - The effect of crystallite size on the thermal phase change and porous properties
      of boehmite was investigated using boehmites with crystallite sizes of 2.9 to
      24.4 nm and boehmite gels prepared by precipitation and hydrothermal methods. The
      dehydroxylation temperature of boehmite increases, its phase transition
      temperature from gamma- to theta-Al(2)O(3) decreases and the theta- to alpha
      Al(2)O(3) transition temperature increases as the crystallite size of the
      boehmite increases. Boehmite with a crystallite size of approximately 5 nm shows
      the highest specific surface area and greatest thermal stability. This boehmite
      contains pores of about 2-3 nm radius, suggested to be responsible for the
      superior porous properties and thermal stability.

PMID- 16290511
TI  - On the characterization of chemical surface groups of carbon materials.
AB  - This paper deals with the use of several methods to characterize the chemical
      surface groups of carbon materials. Several samples embracing a wide range of
      acidic and basic characteristics have been used for this purpose. The
      quantitative determinations have been carried out by selective titrations in
      aqueous solutions, thermal programmed desorption connected to mass spectrometry
      (TPD-MS), and ammonia adsorption-desorption, measured by thermogravimetry (TG).
      The results show some inconsistencies between the different experimental methods.
      These mainly arise because chemical transformations can be produced during the
      experiments. Moreover, the textural characteristics of the carbon materials and
      the existence of pi electrons on the graphitic planes are important factors to be
      considered in the discussion of the results.

PMID- 16290512
TI  - Isomerization of n-hexane over silica-supported heteropoly acids promoted by the
      reduced Ce-Ni oxides.
AB  - The structure and catalytic properties of silica-supported heteropoly acids
      promoted by the reduced Ce-Ni oxides are first studied by using chemical analysis
      XRD, FT-Raman, XPS, EPR, TG, surface area measurements, and microreactor test. It
      is found that silica-supported heteropoly acids have isomerization activity, but
      are very easy to deactivate by coke deposition. With the promotion of the reduced
      Ce-Ni oxides, however, the better activity and the higher selectivity to isomers
      could be obtained, suggesting that the reduced Ce-Ni oxides really have
      hydrogenating/dehydrogenating functions. Moreover, it is found that the presence
      of the reduced Ce-Ni oxides is not only beneficial for eliminating the coke
      deposition, but also effective for maintaining the structure of silica-supported
      heteropoly acids during reaction. The effect of the composition of the mechanical
      mixtures of silica-supported heteropoly acids and the Ce-Ni oxides on the
      catalytic properties has been explored.

PMID- 16290513
TI  - Reduction of colloidal manganese dioxide by manganese(II).
AB  - The reduction of colloidal MnO(2) by Mn(2+) in aqueous HClO(4) has been studied
      by a spectrophotometric method. The reaction product is Mn(III). The reaction is
      of first order in both colloidal MnO(2) and H(+), whereas it presents a
      fractional order (0.58+/-0.02) in Mn(2+). The reaction is retarded by addition of
      NaClO(4), but is not affected by addition of tert-butanol. The corresponding
      activation energy is 29.5+/-1.3 kJ mol(-1). The reaction is catalyzed by
      Na(4)P(2)O(7), and the pyrophosphate-catalyzed reaction is of first order in both
      colloidal MnO(2) and pyrophosphate and of fractional order (0.64+/-0.01) in
      Mn(2+), whereas its rate presents a complex dependence on the concentration of
      H(+). The pyrophosphate-catalyzed reaction is accelerated by addition of both
      NaClO(4) and tert-butanol. The corresponding activation energy is 49.7+/-3.0 kJ
      mol(-1). Mechanisms in agreement with the experimental data are proposed for both
      the parent and the pyrophosphate-catalyzed reactions.

PMID- 16290515
TI  - Estimation of trioctylphosphine oxide (TOPO) diffusion coefficients by dynamic
      adsorption measurements in model extraction systems.
AB  - Equilibrium interfacial tension and surface excess isotherms for
      trioctylphosphine oxide (TOPO) were determined and interpreted. Despite its high
      hydrophobicity, TOPO adsorbs at the hydrocarbon/water interfaces and decreases
      effectively the interfacial tension. The interfacial activity of TOPO is affected
      by the type of organic diluent and the composition of the aqueous phase, i.e.,
      the kind (HNO(3), KNO(3)) and the concentration of nonorganic electrolyte present
      in the system. Significant lowering of TOPO interfacial activity is observed with
      an increase of the aqueous phase acidity. The dynamic interfacial tension for
      TOPO was measured by using the drop volume technique. With the aid of the Ward
      and Tordai equation the values of the diffusion coefficients of TOPO were
      estimated. The values determined were in the right order of magnitude compared
      with the literature data.

PMID- 16290514
TI  - Water contact angles and hysteresis of polyamide surfaces.
AB  - The wetting behavior of a series of aliphatic polyamides (PAs) has been examined.
      PAs with varying amide content and polyethylene (PE) were molded against glass to
      produce surfaces with similar roughness. After cleaning, chemical composition of
      the surfaces was verified with X-ray photoelectron spectroscopy. Advancing and
      receding contact angles were measured from small sessile water drops. Contact
      angles decreased with amide content while hysteresis increased. Hysteresis arose
      primarily from molecular interactions between the contact liquid and the solid
      substrates, rather than moisture absorption, variations in crystallinity, surface
      deformation, roughness, reorientation of amide groups, or surface contamination.
      Free energies of hysteresis were calculated from contact angles. For PE, which is
      composed entirely of nonpolar methylene groups, free energies were equivalent to
      the strength of dispersive van der Waals bonds. For PAs, free energies
      corresponded to fractional contributions from the dispersive methylene groups and
      polar amide groups.

PMID- 16290516
TI  - Chlorpromazine and sodium dodecyl sulfate mixed micelles investigated by small
      angle X-ray scattering.
AB  - Small-angle X-ray scattering (SAXS) studies are reported on the interaction of
      chlorpromazine (CPZ) with micelles of anionic surfactant sodium dodecyl sulfate
      (SDS). Isotropic solutions of SDS (40 and 100 mM) at pH 4.0, 7.0, and 9.0 in the
      absence and presence of CPZ (2-25 mM) were investigated at the National
      Laboratory of Synchrotron Light (LNLS, Campinas, Brazil). The data were analyzed
      through the modeling of the micellar form factor and interference function. The
      results evidence a micellar shape transformation from prolate ellipsoid to
      cylinder accompanied by micellar growth and surface charge screening as the molar
      ratio CPZ : SDS increases in the complex. Small ellipsoids with axial ratio
      nu=1.5+/-0.1 at 40 mM SDS grow and reassemble into cylinder-like aggregates upon
      5 mM drug incorporation (1 CPZ : 8 SDS monomers) with a decrease of the micelle
      surface charge. At 10 mM CPZ : 40 mM SDS cylindrical micelles are totally
      screened with an axial ratio nu approximately 2.5. The data also indicate the
      presence of small prolate ellipsoids (nu=1.7+/-0.1) in solutions of 100 mM SDS
      (no drug) and micellar growth (nu approximately 2.0 and 4.0) when 10 and 25 mM
      CPZ are added to the system. In the latter case, the aggregate is also better
      represented by a cylinder-like form. Therefore, our results demonstrate that the
      axial ratio and shape evolution of the surfactant : phenothiazine complex are
      both SDS concentration and drug : SDS molar ratio dependent. The drug location
      close to the SDS polar headgroup region without disrupting in a significant way
      both the paraffinic hydrophobic core and the polar shell thickness is inferred.
      SAXS data made it possible to obtain the shapes and dimensions of CPZ/SDS
      aggregates.

PMID- 16290517
TI  - Influence of the structure of the hydrophobe on the ideality of mixing in
      micelles in binary mixtures of amphiphilic tricyclic drugs.
AB  - The composition of the micelles in binary mixtures of the cationic amphiphilic
      antidepressant drugs nortriptyline, amitriptyline, and doxepin has been
      determined from an analysis of the variation of the critical micelle
      concentration from conductivity measurements, as a function of solution
      composition. Assessment of the nonideality of mixing in terms of the interaction
      parameter from the regular solution approximation showed small deviations from
      ideal mixing, with negative interaction parameters for
      nortriptyline/amitriptyline systems and positive interaction parameters for
      mixtures of nortriptyline and doxepin. These differences in nonideality have been
      attributed to differences in the packing of the drugs in the mixed micelles
      arising from differences in the structure of the hydrophobe.

PMID- 16290518
TI  - Glucose encapsulation in catanionic vesicles and kinetic study of the
      entrapment/release processes in the sodium dodecyl benzene
      sulfonate/cetyltrimethylammonium tosylate/water system.
AB  - The sodium dodecyl benzene sulfonate (SDBS)/cetyltrimethyl-ammonium tosylate
      (CTAT)/water ternary system has previously been shown to give rise to the
      formation of vesicles for well-defined compositions requiring an excess of one of
      the surfactants over the other. Two types of vesicular systems can thus be
      obtained (named V(+) and V(-), depending on the nature of the excess surfactant,
      i.e., CTAT or SDBS, respectively). In addition, the pure ion-pair amphiphile
      (IPA) can be obtained after removing the counterions. These different systems
      (V(+), V(-), and IPA) were investigated in regards to their ability to
      susbtantially retain a hydrophilic probe such as glucose. The influence of the
      initial glucose and surfactant concentrations was studied, and dialysis
      experiments were conducted with a view to determine the kinetics of glucose
      entrapment and release by the vesicles and, thus, to assess the possibility of a
      long-term encapsulation. The results indicate that all the vesicular systems
      studied here are characterized by quite a high permeability of the amphiphilic
      bilayer. However, SDBS-rich (V(-)) and IPA vesicles proved to be less permeable
      than CTAT-rich (V(+)) vesicles.

PMID- 16290519
TI  - Micellar effects on dediazoniation and on azo coupling reactions.
AB  - The effects of a sodium dodecyl sulfate, SDS, micellar solution on the coupling
      rates of two arenediazonium ions, ArN(2)(+), with the hydrophobic 1
      naphthylamine, 1NA and N-(1-naphthyl) ethylenediamine, NED, coupling agents and
      with the hydrophilic Na salt of 2-naphthol-6-sulfonic acid, 2N6S, have been
      studied. First, we explored the micellar effects on the thermal decomposition of
      the arenediazonium ions. The observed rate constants are slightly depressed or
      increased, depending on the nature of ArN(2)(+), compared to those in pure water
      upon increasing [SDS]. Estimations of the corresponding association constant to
      the micelle indicate that a significant fraction of the arenediazonium ions are
      incorporated into the micelles even at low surfactant concentrations. The
      sulfonate group in 2N6S prevents its incorporation into the micellar aggregate
      due to the electrostatic barrier imposed by the micelles and, in consequence, the
      coupling reaction is inhibited. In contrast, when employing the naphthylamine
      derivatives, the observed rate constant increase rapidly up to a maximum at
      [SDS]</=0.01 M and then decreases smoothly due to the dilution effect exerted by
      the micelles. The results are discussed in terms of the distribution of reactants
      between the micellar and aqueous pseudophases, the micellar-induced shift in the
      pK(a) of the amines, and the concentration/dilution effect exerted by the
      micelles.

PMID- 16290520
TI  - Electrokinetic flow through an elliptical microchannel: effects of aspect ratio
      and electrical boundary conditions.
AB  - The electrokinetic flow of an electrolyte solution through an elliptical
      microchannel is studied theoretically. The system under consideration simulates
      the flow of a fluid, for example, in vein. We show that, for a constant cross
      sectional area, both the electroosmotic volumetric flow rate and the streaming
      potential increase monotonically with an increase in the aspect ratio, and both
      the total electric current and the electroviscous effect may exhibit a local
      minimum as the aspect ratio varies. Also, for a constant average potential on the
      channel wall, the difference between the results based on three kinds of boundary
      conditions, which include constant surface charge, constant surface potential,
      and charge-regulated surface, is inappreciable if the hydraulic diameter is
      larger than 1 mum.

PMID- 16290521
TI  - Coexistence of liquid phases in the sodium polyphosphate-chromium nitrate-water
      system.
AB  - The formation of coexisting liquid phases out of aqueous aluminum polyphosphate
      solutions was previously suggested as an essential step in aluminum polyphosphate
      nanoparticle formation. This hypothesis could not be directly verified because
      the separation of the two phases is very difficult, but a different situation was
      found in the case of chromium (III) polyphosphate. The phase diagram of the
      sodium polyphosphate-chromium nitrate-water system at 25 degrees C presents an
      extensive region with two coexisting liquid phases (L-L), together with a single
      liquid phase (L) and a solid-liquid (S-L) domain. Within the L-L region,
      admixture of the reagents produces initially a turbid liquid, out of which two
      transparent liquid phases separate in a short time, under gravity: one is dense,
      dark, and viscous while the other has a light color and a lower density. The
      amounts of the separated phases were determined, as well as their viscosities,
      densities, pH, UV-vis spectra, and relevant molalities: P (from polyphosphate),
      Cr(3+), NO(-)(3+), and Na(+). The two liquid phases undergo significant color,
      pH, and viscosity changes with time. The calculated phase diagrams display the
      major features of the experimental phase diagram.

PMID- 16290522
TI  - Controlled drug release from gels using lipophilic interactions of charged
      substances with surfactants and polymers.
AB  - The aim of this article was to study interactions between different gel forming
      polymers and amphiphilic drugs and surfactants with the intention of finding
      interactions that can be used for designing controlled release formulations. The
      release from gels was measured by detecting the UV-absorbance of drugs released
      from 6 mL gel into 250 mL release medium in a dissolution bath. The rheological
      behavior of gels was characterized using a controlled rate rheometer. The
      diffusion coefficient of alprenolol was 6.3 x 10(-6) cm(2)/s when formulated in a
      1% poly(acrylic acid) gel (PAA) and 2.8 x 10(-6) cm(2)/s in a lipophilically
      modified gel (LM-PAA). The addition of alprenolol to 1% LM-PAA increased the
      elasticity, G', from 123 to 182 Pa. Increased gel strength was also observed for
      a number of other amphiphilic drugs. The addition of 1% Brij 58 to LM-PAA
      decreased the diffusion coefficient of alprenolol to 2.3 x 10(-6) cm(2)/s. It was
      possible to sustain the release of charged drugs with high log P by adding
      surfactant micelles. However, the effect was small and only useful for drugs with
      adequate lipophilicity. The interaction between LM-PAA and amphiphilic drugs
      could be seen using rheology and was used for designing controlled release gel
      formulations. In this way surfactants can be avoided, thus decreasing toxicity
      problems.

PMID- 16290524
TI  - Dimeric (gemini) surfactants: effect of the spacer group on the association
      behavior in aqueous solution.
AB  - Dimeric (gemini) surfactants are made up of two amphiphilic moieties connected at
      the level of, or very close to, the head groups by a spacer group of varying
      nature: hydrophilic or hydrophobic, rigid or flexible. These surfactants
      represent a new class of surfactants that is finding its way into surfactant
      based formulations. The nature of the spacer group (length, flexibility, chemical
      structure) has been shown to be of the utmost importance in determining the
      solution properties of aqueous dimeric surfactants. This paper reviews the effect
      of the nature of the spacer on some of these properties. The behavior of dimeric
      surfactants in the submicellar range of concentration, at interfaces, in dilute
      solution (solubility in water, Krafft temperature, critical micellization
      concentration, thermodynamics of micelle formation, micelle ionization degree,
      size, polydispersity, micropolarity and microviscosity, microstructure and
      rheology of the solutions, solubilization, micelle dynamics, and interaction with
      polymers) and in concentrated solution (phase behavior) are successively
      reviewed. Selected results concerning trimeric and tetrameric surfactants are
      also reviewed.

PMID- 16290525
TI  - Cation exchange and sorption properties of crystalline alpha-titanium(IV)
      phosphate.
AB  - The ion-exchange and sorption properties of alpha-titanium bis(monohydrogen
      orthophosphate) monohydrate of composition Ti(HPO(4))(2).H(2)O was studied in
      aqueous electrolyte solutions of KCl over the temperature range of 300-320 K,
      varying the pH and metal ion concentration in the solution. The data were
      explained on the basis of the law of chemical equilibrium and the metal ion
      sorption data were fitted to Langmuir parameters. Further, the extent of sorption
      was found to increase with increasing temperature and metal ion concentration in
      the selectivity order Fe(3+)>Cu(2+)>Co(2+)>Mn(2+)>Cr(3+)>Ni(2+). The values of
      Langmuir constants were used to calculate the various thermodynamic parameters,
      such as DeltaG(0), DeltaH(0), and DeltaS(0), during the sorption process.

PMID- 16290526
TI  - Delamination behavior of silicate layers by adsorption of cationic surfactants.
AB  - Smectite that has reacted for 48 h with hexadecyltrimethylammonium (HDTMA)
      cations equivalent to 0.01-3.0 times the cation exchange capacity (CEC) converts
      to HDTMA-smectite. The microstructure of this organoclay is observed using X-ray
      diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM).
      When Na cations in the interlayer of clay are exchanged with HDTMA ions, the
      changes in internal and external surface configuration are augmented by the
      intercalation of organic surfactants, showing a heterogeneous increase of
      interlayer spacings. As HDTMA loading increases, the chance of delaminated layers
      being developed increases locally in the low-charge interlayer regions by the
      sufficient adsorption of organic surfactants beyond the CEC due to the tendency
      of alkyl chain interaction.

PMID- 16290527
TI  - Solid-state fluorescence study of naphthalene adsorption on porous material.
AB  - Naphthalene adsorption profile on porous materials was studied using solid-state
      fluorescence spectroscopy. When naphthalene crystals were simply mixed with
      porous crystalline cellulose (PCC), excimer emission of naphthalene was observed
      after 1 min of mixing, suggesting a drastic change in the naphthalene molecular
      environment during the mixing procedure. For the naphthalene-octadesyl silane
      (ODS)-80A or naphthalene-ODS-2 systems, the changes in adsorption profiles and
      fluorescence spectral pattern of naphthalene were similar to those of the
      naphthalene-PCC system. The final amounts of naphthalene adsorbed to ODS-80A and
      ODS-2 were 0.05 and 0.024 g/g adsorbent, respectively, even though the two
      materials had comparable values of specific surface area. The relative emission
      intensity (I(excimer)/I(monomer)) in the ODS-80A system was higher than that in
      the ODS-2 system when compared at the same amount of naphthalene adsorbed. It was
      concluded that the pore size of porous materials affected the naphthalene excimer
      formation on the surface.

PMID- 16290528
TI  - Deposition of particles in the impinging-jet cell for the high coverage regime.
AB  - Particle deposition in the radial impinging-jet cell for the high coverage regime
      was studied theoretically and experimentally. A detailed description of the flow
      distribution in the cell was attained by solving the governing Navier-Stokes
      equation numerically. The macroscopic flow pattern was decomposed into simpler
      local flows. It was demonstrated that for tangential distances r/R>0.5 the
      overall flow at the interface was dominated by the simple shear. The intensity of
      this flow was calculated numerically as a function of the Reynolds number and the
      distance from the cell center. Knowing the fluid velocity field the convective
      diffusion equation was formulated describing a two-dimensional transport of
      particles. As a result of nonlinearity of the boundary condition this equation
      was solved in an exact manner for low coverage only. For higher coverage,
      approximate methods were proposed exploiting the random sequential adsorption
      (RSA) approach. The validity of the theoretical predictions was verified
      experimentally using the direct microscope observation method and polystyrene
      latex particles of the size 0.87 mum. Particle coverage distribution was studied
      in detail as a function of the Re number governing the local shear rate. It was
      demonstrated that for low Re number (Re<4) uniform particle monolayers of high
      coverage can be attained. On the other hand, for Re>8 the particle coverage
      distribution became nonuniform as a result of the hydrodynamic scattering. This
      effect, leading to an apparent kinetic saturation of the surface at coverages of
      a few percents, was quantitatively interpreted in terms of the theoretical model.

PMID- 16290529
TI  - NMR and monte carlo simulation studies of water adsorption dynamics.
AB  - Nuclear magnetic resonance water proton spin-spin relaxation time T(2) was
      measured in wood samples with moisture contents ranging from 0.50 to 26.4%. The
      experimental results are discussed in terms of Monte Carlo simulations, which
      determine the correlation times tau for reorientation of the water molecule
      proton-proton vectors. We demonstrate that 1/T(2) and tau qualitatively follow
      the same behavior with surface hydration. The common application of the multisite
      exchange model to hydrated systems is discussed in light of the new results.

PMID- 16290530
TI  - On the adsorption behavior of soluble, surface-chemically pure hemicyanine dyes
      at the air/water interface.
AB  - Equilibrium surface tension (sigma(e)) versus concentration isotherms of surface
      chemically pure aqueous solutions of the homologous series of N-n-alkyl-4'
      (dimethylamino)-stilbazium bromides ("hemicyanines") were measured at 295 K. The
      adsorption parameters of saturation adsorption and standard free energy of
      adsorption of the hemicyanines were determined from the evaluation of the
      sigma(e) vs c isotherms using a two-state approach to the surface equation of
      state. The adsorption parameters reveal a very pronounced phenomenon of
      alternation (even/odd effect), which has so far not been found to a large extent
      such as this. Thus, the cross-sectional areas of the odd members are almost twice
      those of the related even members. Surface activity of the odd members is
      stronger than that of the even members. UV-vis investigations showed that there
      is no indication of aggregate formation in the adsorption layer. The
      thermodynamic results give evidence for distinct differences between the surface
      conformations of the even- and the odd-chain hemicyanine dyes although the
      reasons for this are not known.

PMID- 16290531
TI  - Adsorption of fluoride, phosphate, and arsenate ions on a new type of ion
      exchange fiber.
AB  - A new type of ion exchange fiber for the removal of fluoride, phosphate, and
      arsenate ions has been developed. A batch adsorption technique for investigating
      adsorption kinetic and equilibrium parameters and determining pH adsorption edges
      is applied. It is shown that the adsorption properties of the ion exchange fiber
      for fluoride, phosphate, and arsenate ions depend on the pH value and anion
      concentration. The adsorption of arsenate on the sorbent reaches a maximum of
      97.9% in the pH value range of 3.5 to 7.0. The adsorption percentage of phosphate
      is more than 99% in the pH range of 3.0 to 5.5. The adsorption of fluoride on the
      ion exchange fiber is found to be 90.4% at pH 3.0. The Freundlich model can
      describe the adsorption equilibrium data of fluoride, arsenate, and phosphate
      anions. The sorption of the three anions on the ion exchange fiber is a rapid
      process, and the adsorption kinetic data can be simulated very well by the pseudo
      second-order rate equation. The column performance is carried out to assess the
      applicability of the ion exchange fiber for the removal of fluoride, phosphate,
      and arsenate ions from synthetic wastewaters with satisfactory removal
      efficiency. The desorption experiment shows that fluoride ion sorbed by the fiber
      column can be quantitatively desorbed with 5 mL of 0.50 mol/L NaOH at elution
      rate of 1 mL/min, and 30 mL of NaOH is necessary for the quantitative recovery of
      phosphate and arsenate ions.

PMID- 16290532
TI  - Pb(II) sorption onto gamma-Al2O3 surfaces at the oxide-water interface: a novel
      approach using planar oxides.
AB  - A novel technique for examining metal-ion interactions at the solid-water
      interface is introduced. Planar oxides, flat, thin coatings of uniform thickness
      created on a metal support, have been constructed as useful analogs for
      investigating metal-solid interactions under a variety of conditions. XPS and
      ToF/SIMS results from sorption studies at pH 6.0 show that the sorption behavior
      of Pb on each phase is similar with Pb binding preferentially to the bulk gamma
      Al(2)O(3). This may be due to the presence of defect sites on the bulk oxides,
      the preferential exposure of a specific crystallographic plane in the planar
      oxides, or it may be an artifact of instrumental analysis. A second study
      examining Pb sorption to planar gamma-Al(2)O(3) under a series of increasingly
      complex conditions shows that our methods are able to successfully characterize
      sorption complexes formed in the presence of environmentally derived complexants.
      Results suggest that Pb is more strongly complexed by aqueous phase organic
      matter than sediment-bound organic material, indicating a possible control on Pb
      sorption in natural environments. Overall, the use of planar oxides combined with
      a powerful suite of spectroscopic tools provides a promising approach to better
      understanding metal ion sorption to natural sediment surfaces in aquatic
      environments.

PMID- 16290533
TI  - Kinetic derivation of the electromigration equation for aerosol particles in the
      presence of bipolar charging.
AB  - The spatial and temporal evolution of the charge distribution on aerosol
      particles undergoing bipolar charging due to small ions in the presence of
      electric fields is generally described by a charging equation set up in charge
      position space. Being a phenomenological description, this requires to be derived
      from a more fundamental kinetic description by explicitly incorporating Brownian
      velocity fluctuations in position-velocity-charge space. This paper presents such
      a derivation and obtains correction factors for the conventionally used mobility
      and diffusion coefficients in the charging equation. Although mobility correction
      is negligible for small particles at low ion concentrations, it is significant
      for particles of sizes above 10 microm at high ion densities (>10(6)/cc). The
      analysis predicts a new electrical diffusion mechanism in addition to Brownian
      diffusion, which arises as a result of dispersion in the electromigration
      velocities of particles having the same charge. This mechanism is contrasted with
      the charging-induced diffusion mechanism proposed earlier by Y. S. Mayya and S.
      V. Malvankar (J. Colloid Interface Sci.156, 78, 1993). The electrical diffusion
      coefficients and the corresponding velocity persistence lengths are several
      orders higher than their Brownian counterparts. The study also obtains the
      boundary conditions to be employed for computing charge particle deposition rates
      near absorbing surfaces and discusses specific solutions.

PMID- 16290534
TI  - The self-preserving size distribution theory. I. Effects of the Knudsen number on
      aerosol agglomerate growth.
AB  - Gas-phase synthesis of fine solid particles leads to fractal-like structures
      whose transport and light scattering properties differ from those of their
      spherical counterparts. Self-preserving size distribution theory provides a
      useful methodology for analyzing the asymptotic behavior of such systems.
      Apparent inconsistencies in previous treatments of the self-preserving size
      distributions in the free molecule regime are resolved. Integro-differential
      equations for fractal-like particles in the continuum and near continuum regimes
      are derived and used to calculate the self-preserving and quasi-self-preserving
      size distributions for agglomerates formed by Brownian coagulation. The results
      for the limiting case (the continuum regime) were compared with the results of
      other authors. For these cases the finite difference method was in good in
      agreement with previous calculations in the continuum regime. A new analysis of
      aerosol agglomeration for the entire Knudsen number range was developed and
      compared with a monodisperse model; Higher agglomeration rates were found for
      lower fractal dimensions, as expected from previous studies. Effects of fractal
      dimension, pressure, volume loading and temperature on agglomerate growth were
      investigated. The agglomeration rate can be reduced by decreasing volumetric
      loading or by increasing the pressure. In laminar flow, an increase in pressure
      can be used to control particle growth and polydispersity. For D(f)=2, an
      increase in pressure from 1 to 4 bar reduces the collision radius by about 30%.
      Varying the temperature has a much smaller effect on agglomerate coagulation.

PMID- 16290536
TI  - Deposition of spherical particles onto cylindrical solid surfaces. I. Numerical
      simulations.
AB  - In this article, analytical and numerical solutions are given for the deposition
      of spherical particles onto cylindrical solid surfaces. If only the retarded van
      der Waals (vdW) force and the electrical double-layer (EDL) force between the
      spherical particle and the cylindrical surface are considered, such a deposition
      process is governed by a one-dimensional (1D) mass transfer equation for which
      both analytical and numerical solutions are obtained. A parametric study was
      conducted to examine the effects of these two colloidal forces on the deposition
      process. The numerical results show that the attractive vdW force, as represented
      by the dimensionless adhesion number A(d), is a necessary condition for
      deposition to occur. However, it affects only the drop number concentration
      distribution and, to a limited extent, the mass transfer rate. In general, the 1D
      deposition process is dominated by the EDL force, as represented by the
      dimensionless EDL parameter Dl and the reduced radius tau=kappaa of the spherical
      drop. It is noted that tau plays a key role in determining the effect of the EDL
      force on the mass transfer rate since an appreciable EDL force exists only within
      small separation distances (</=3tau(-1)). In addition to the two colloidal
      forces, the deposition process was also investigated in the presence of gravity
      and with a vertically applied electrical force. With these two external forces,
      the deposition becomes a two-dimensional (2D) boundary value problem for which a
      numerical solution was achieved using the implicit Crank-Nicolson method. Their
      effects on the 2D deposition process were studied.

PMID- 16290535
TI  - The self-preserving size distribution theory. II. Comparison with experimental
      results for Si and Si3N4 aerosols.
AB  - The gas to particle synthesis route is a relatively clean and efficient manner
      for the production of high-quality ceramic powders. These powders can be
      subsequently sintered in any wanted shape. The modeling of these production
      systems is difficult because several mechanisms occur in parallel. From
      theoretical considerations it can be determined, however, that coagulation and
      sintering are dominant mechanisms as far as shape and size of the particles are
      considered. In part I of this article an extensive theoretical analysis was given
      on the self-preserving size distribution theory for power law particles. In this
      second part, cumulative particle size distributions of silicon and silicon
      nitride agglomerates, produced in a laser reactor, were determined from TEM
      pictures and compared to the distributions calculated from this self-preserving
      theory for power law particles. The calculated distributions were in fair
      agreement with the measured results, especially at the high end of the
      distributions. Calculated and measured particle growth rates were also in fair
      agreement. Using the self-preserving theory an analysis was made on the
      distribution of annealed silicon agglomerates, of interest in applications to
      nanoparticle technology.

PMID- 16290537
TI  - Deposition of spherical particles onto cylindrical solid surfaces. II.
      Experimental studies.
AB  - This paper presents experimental studies of the deposition of silicone oil drops
      onto two different solid surfaces in an aqueous solution. A series of deposition
      tests were conducted to measure the dimensionless mass transfer rate (Sherwood
      number). The effects of three kinds of aqueous solutions and two solid surfaces
      on the deposition process were studied and compared with the numerical
      predictions based on the well-known DLVO theory. More specifically, both the
      experimentally measured and the numerically predicted Sherwood numbers
      monotonically decrease as the pH value of the aqueous solution increases. It was
      also found that two ionic surfactant solutions have similar influences while the
      electrolyte solutions have opposite effects on the deposition rate on different
      solid surfaces. Finally, comparison of all the experimental results for the bare
      glass surface with the numerical simulations shows that the deposition process of
      the silicone oil drops onto the hydrophilic solid surface can be satisfactorily
      described by the classical DLVO theory. However, the deposition data for the
      FC725 precoated surface are significantly larger than the numerical predictions.
      This fact suggests that the so-called non-DLVO attractive interaction is involved
      in the deposition process with the hydrophobic solid surface. This additional non
      DLVO attractive interaction, which is generally called the hydrophobic
      interaction, still remains to be incorporated into the existing DLVO theory, if
      this is possible.

PMID- 16290538
TI  - Quantification of microstructures in stable and gelated suspensions from Cryo
      SEM.
AB  - It is shown that the microstructures of concentrated suspensions can be analyzed
      in a quantitative way from cryo-SEM images of high-pressure frozen samples, both
      in the electrostatically stabilized and in the flocculated state. Suspensions of
      spherical silica particles (40 vol%) in an aqueous solution were used. The
      average particle radius was 525 nm with a polydispersity of below 7%. The
      suspensions were high-pressure frozen, which resulted in a quenching of the
      configuration without apparent change in volume or crack formation. After
      fracturing the samples at liquid nitrogen temperature, the fracture surface was
      etched by controlled sublimation of the frozen aqueous phase, coated with 8 nm of
      platinum, and examined by stereo-cryo-SEM. The 3-dimensional positions of all the
      visible particles were determined from the SEM images. Assuming an isotropic
      particle configuration in the sample before cracking, it is possible to extract
      the 3-dimensional pair correlation function from the particle positions on the
      fracture surface. A comparison to recent results from Brownian Dynamics
      simulations shows good agreement between our experiments and the simulations.

PMID- 16290539
TI  - The adsorption and condensed film formation of cetyltrimethylammonium bromide at
      the mercury/electrolyte interface.
AB  - The adsorption of cetyltrimethyammonium bromide (CTAB) on a hanging mercury
      electrode is studied in various electrolyte systems and temperatures. A condensed
      film is formed at negative potentials and at room temperature only in the
      presence of KBr. The decrease of the temperature favors the formation of the
      condensed film. Hysterisis phenomena are observed during the potential scans at
      both directions. Capacity time curves at the potentials where the film is formed
      show a nucleation and growth mechanism, with induction time depending on
      potential, which has been investigated using Avrami formulation and has been
      explained as a progressive one-dimensional nucleation with constant growth rate.
      The nucleation rate increases while moving toward more negative potentials. A
      linear decrease of the capacitance with time was observed in some cases
      independent of the measuring potential in a relative large potential range. The
      different types of micelles can affect the adsorption of CTAB on mercury. An
      unusual capacitance transient observed at a very narrow negative potential range
      is attributed to the formation of hemicylinders. The condensed film in the
      presence of the other electrolytes is observed only at high concentrations (1 M)
      and very low temperatures (5 degrees C).

PMID- 16290540
TI  - A simple Maxwell-Wagner-Butler-Volmer approach to the impedance of the hydrogen
      electrode in a nafion fuel cell.
AB  - A simple one-dimensional model of the impedance of a hydrogen/Nafion electrode is
      set up combining the usual Maxwell-Wagner approach for linear, homogeneous, and
      isotropic media with the linearized Butler-Volmer equation for the interfacial,
      electrochemical reaction. Only one relaxation semicircle is normally seen in the
      Nyquist diagram, but a low-frequency arc may appear at high overvoltages. The
      model is described by only two dimensionless parameters (in addition to the
      dimensionless frequency). These parameters are related to the double-layer
      capacitance and to the interfacial electrochemical reaction rate, respectively.
      With some adjustments, the model can be used to explain the observed equilibrium
      impedance from 40 to 70 degrees C of a symmetric cell of the type
      C/Pt/H(2)|Nafion 117/H(2)/Pt/C. The hydrogen electrodes in this cell were built
      up as a disperse multiphase region (carbon, platinum grains, Nafion 117, and
      hydrogen gas) as commonly done in solid polymer fuel cells.

PMID- 16290541
TI  - Electrochemical behavior of Au colloidal electrode through layer-by-layer self
      assembly.
AB  - Electrodes formed by Au colloidal nanoparticles have been obtained by layer-by
      layer self-assembly using 1,6-hexanedithiol as cross-linkers. Cyclic
      voltammograms show that the peak-to-peak separation decreases as the number of Au
      colloidal layers increases. After seven layers of Au colloidal particles have
      been deposited, the multilayer electrodes have the electrochemical properties of
      metallic Au and show ideal microelectrode behavior. An equivalent circuit for the
      electrochemical impedance spectroscopy was established to model the working
      electrode. It is evident that by increasing the layer number of Au colloidals,
      the interfacial electron transfer is promoted, implying the electron-transfer
      process changes from a kinetically limited process to a diffusionally limited
      process.

PMID- 16290542
TI  - Electrophoresis of a sphere normal to a plane at arbitrary electrical potential
      and double layer thickness.
AB  - The electrophoretic movement of a sphere normal to an uncharged, planar surface
      is analyzed theoretically, taking the effect of double layer polarization into
      account. Here, both the surface potential of the particle and the thickness of
      the double layer surrounding it can be arbitrary. We show that if double layer
      polarization is neglected, the effect of the surface potential of a particle on
      its electrophoretic velocity is inappreciable. On the contrary, it becomes
      significant if double layer polarization is present. However, if the distance
      between the particle and the surface is sufficiently close, since the
      hydrodynamic effect dominates, the influence of the surface potential and double
      layer polarization becomes insignificant.

PMID- 16290543
TI  - Hamaker constants in integrated circuit metalization.
AB  - A new method for determining Hamaker constants was examined for materials of
      interest in integrated circuit manufacture. An ultra-high vacuum atomic force
      microscope and an atomic force microscope operated in a nitrogen environment were
      used to measure the interaction forces between metals, dielectrics, and barriers
      used during the metalization portion of integrated circuit manufacturing. The
      materials studied included copper, silver, titanium nitride, silicon dioxide,
      poly(tetrafluoroethylene), and parylene-N. Spheres coated with a material of
      interest were mounted on AFM cantilevers and brought into contact with substrates
      of interest. The interaction force was measured as the cantilever approached the
      substrate but before the two surfaces came into contact, and also when the
      particle was pulled out of contact with the substrate. The Hamaker constant
      calculation from the contact measurement is based on an adhesion model that
      quantifies the contribution of geometrical, morphological and mechanical
      properties of materials to the measured adhesion force. Hamaker constants
      determined with this new approach were compared with values found by using the
      Derjaguin approximation for a sphere to describe the interaction force as the
      cantilever approaches the surface. Both approaches produced similar values for
      most of the systems studied, with variations of less than 10%.

PMID- 16290544
TI  - Electrophoresis of a concentrated spherical dispersion at arbitrary electrical
      potentials.
AB  - The electrophoretic behavior of a concentrated spherical dispersion is
      investigated theoretically. The present analysis extends those in the literature
      in that both the surface potential of a particle and the strength of the applied
      electric field are arbitrary and both the effects of double-layer polarization
      and the overlapping between neighboring double layers are taken into account.
      Results based on these conditions are highly desirable since they cover
      essentially all the possible experimental conditions in practice. We show that,
      for a fixed surface potential and strength of applied electric field, the higher
      the concentration of particle, the smaller the mobility. Counterions are found to
      accumulate at the downstream side of a particle. Double-layer polarization is
      inappreciable if either it is thick or the concentration of the particle is high.

PMID- 16290545
TI  - Application of electromodulated fluorescence to the study of the dynamics of
      single-strand oligonucleotides at modified gold surfaces.
AB  - Single-strand oligonucleotides with fluorescein labels were immobilized on
      modified gold electrodes and the surface fluorescence intensity was measured as a
      function of the potential applied to the electrode. The potential consisted of a
      constant and sinusoidal parts. The fluorescence was detected synchronously with
      the sinusoidal component of the potential. Large variation in the
      electromodulated fluorescence (EmF) was observed as a function of the constant
      component of the applied potential. In the potential range -0.2 to +0.2 V (vs
      Ag/AgCl) the EmF signal was quasi-reversible. A model for surface fluorescence
      was applied to the analysis of the EmF in this potential range. The model assumed
      that the adsorption-desorption process and quenching by the metal were the
      dominant mechanisms responsible for the observed EmF. For constant potential more
      negative than -0.5 V, the observed EmF response appeared to have a contribution
      from ssDNA in solution. This interpretation was suggested by comparison to EmF
      from solutions containing free fluorescein or labeled ssDNA. Large variation in
      the EmF response was observed for electrodes modified with amine and carboxyl
      groups. This suggests that electrostatic interactions play a dominant role.

PMID- 16290546
TI  - In situ polymerized polyaniline films. 4. Film formation in dispersion
      polymerization of aniline.
AB  - Polyaniline films were grown on glass supports during dispersion polymerizations
      of aniline using poly(N-vinylpyrrolidone) and hydroxypropylcellulose as
      stabilizers. The initiation of polyaniline chains is proposed to be
      heterogeneously catalyzed by the surfaces immersed in the reaction mixture. Film
      formations in dispersion and precipitation polymerizations are compared.
      Surfometry and optical absorption were used to assess the submicrometer film
      thickness, and FTIR spectroscopy was used to analyze the chemical structure of
      films and prove the absence of stabilizer. The film thickness was proportional to
      the dimensions of simultaneously produced colloidal polyaniline particles. The
      conductivity of films increased with increasing film thickness.

PMID- 16290547
TI  - Stochastic reconstruction of particulate media from two-dimensional images.
AB  - In this contribution we address the problem of reconstructing particulate media
      from limited morphological information that may be readily extracted from 2D
      images of their microstructure. Sixty-five backscatter SEM images of the
      microstructure of a lightly consolidated pack of glass spheres are analyzed to
      determine morphological descriptors, such as the pore-pore autocorrelation
      function and pore and solid phase chord distributions. This information is then
      used to constrain the stochastic reconstruction of the glass sphere packing in
      two dimensions using a simulated annealing method. The results obtained
      demonstrate that the solid-phase chord distribution contains additional
      information that is critical for the reconstruction of the morphology of
      particulate media exhibiting short-range order. We further confirm this finding
      by successfully reconstructing the microstructure of a pack of irregular silica
      particles.

PMID- 16290549
TI  - Simulation studies of phase inversion in agitated vessels using a Monte Carlo
      technique.
AB  - A speculative study on the conditions under which phase inversion occurs in
      agitated liquid-liquid dispersions is conducted using a Monte Carlo technique.
      The simulation is based on a stochastic model, which accounts for fundamental
      physical processes such as drop deformation, breakup, and coalescence, and
      utilizes the minimization of interfacial energy as a criterion for phase
      inversion. Profiles of the interfacial energy indicate that a steady-state
      equilibrium is reached after a sufficiently large number of random moves and that
      predictions are insensitive to initial drop conditions. The calculated phase
      inversion holdup is observed to increase with increasing density and viscosity
      ratio, and to decrease with increasing agitation speed for a fixed viscosity
      ratio. It is also observed that, for a fixed viscosity ratio, the phase inversion
      holdup remains constant for large enough agitation speeds. The proposed model is
      therefore capable of achieving reasonable qualitative agreement with general
      experimental trends and of reproducing key features observed experimentally. The
      results of this investigation indicate that this simple stochastic method could
      be the basis upon which more advanced models for predicting phase inversion
      behavior can be developed.

PMID- 16290548
TI  - Chemical, structural, and thermal properties of Zn(II)-Cr(III) layered double
      hydroxides intercalated with sulfated and sulfonated surfactants.
AB  - Zn(II)-Cr(III)-LDHs (layered double hydroxides) containing sulfated or sulfonated
      surfactants as the interlamellar anion were synthesized by the coprecipitation
      method. The syntheses were conducted under various different experimental
      conditions, such as the Zn : Cr ratio, pH, and aging time. In each of the
      prepared materials, unlike previously reported data, the interlayer anion
      arrangement did not change, being consistent with a perpendicular monolayer. The
      thermal decomposition process of the prepared materials was studied by a set of
      analysis methods, such as TG/DTA, TG/MS, PXRD, and FT-IR. From the results
      obtained it was possible to conclude that, in an air atmosphere, the anions
      decomposed by a partial combustion, leading to the formation of sulfide. The
      results also showed that sulfonated surfactants containing LDHs are much more
      stable than those containing sulfated surfactants. A mechanism was proposed for
      the thermal decomposition of such LDHs based on the experimental results.

PMID- 16290550
TI  - Kinetic micellar effects in tetradecyltrimethylammonium bromide-pentanol micellar
      solutions.
AB  - The reactions 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane + OH(-) and 2-(p
      nitrophenyl)ethyl bromide + OH(-) were studied in tetradecyltrimethylamonium
      bromide, TTAB, and TTAB-pentanol micellar solutions. The influence of changes in
      the surfactant concentration as well as changes in the hydroxide ion
      concentration on the observed rate constant was investigated. If changes in the
      cmc and ionization degree provoked by the presence of the different amounts of n
      pentanol in the micellar solutions are taken into account, the experimental
      kinetic data can be rationalized quantitatively by using the PIE model. Assuming
      that the ion-exchange equilibrium constant, K(OH(-)/Br(-)), for the competition
      between the bromide and the hydroxide ions in all TTAB and in TTAB-pentanol
      micellar solutions studied is the same, a good agreement between the theoretical
      and the experimental kinetic data was found in all the micellar media for the two
      processes studied. This assumption was checked by experimentally determining the
      ion-exchange equilibrium constant K(OH(-)/Br(-)) in TTAB and TTAB-pentanol
      micellar solutions through a spectroscopic method, results showing that the
      presence of n-pentanol does not affect substantially the value of K(OH(-)/Br(-)).
      The second-order rate constants obtained from the fittings decrease slightly when
      the amount of pentanol increases, being greater than that in aqueous solution.
      This acceleration can be explained considering that micelles accelerate the
      reactions in which the charge is delocalized in the transition state.

PMID- 16290551
TI  - Phase transition in an adsorption layer of a soluble surfactant at the air-water
      interface.
AB  - In this paper we provide experimental evidence for a phase transition between a
      liquid- and gas-like phase occurring in an adsorption layer of a soluble
      surfactant at the air-water interface. The equilibrium surface tension sigma(e)
      versus bulk concentration sigma(e) (c) isotherm of surface chemically pure sodium
      2-[4-(4-trifluoromethyl-phenylazo) phenoxy]-ethane sulfonate was measured at a
      temperature of 295 K up to the solubility limit of the amphiphile. The sigma(e)
      (c) isotherm could be fitted by Frumkin's equation of state. The lateral
      interaction energy is just above the limit for which Frumkin's model predicts a
      phase transition. The corresponding surface pressure pi versus surface area A
      isotherm possesses striking similarities to first-order phase transitions in the
      Langmuir monolayer. The fact that the difference in the two-dimensional density
      is only a factor of 2 indicates that the system is very close to the critical
      point. The surface phases were further characterized by surface second harmonic
      generation. The major structural difference between the two surface phases is the
      amphiphile's molecular orientation. A mean orientation of the amphiphile of about
      80 degrees was found in the gas analogous phase, whereas a molecular tilt of 38
      degrees has been identified in the liquid-like phase.

PMID- 16290552
TI  - Effect of foam films on gas diffusion.
AB  - We report an experimental investigation of the permeability to gas of systems of
      one or several soap films freely standing in a straight tube, using either
      reactive gas (NH(3)) or inert gas (argon). The series of soap films appears to be
      the simplest paradigm of successive lamellae arrangements encountered in foams
      confined in a porous medium. To conduct the experiments, we devised two novel
      methods for the determination of gas diffusion fluxes: one based on reactive
      changes of pH by NH(3) and the other on mass spectrometry. The permeability of a
      single film, stabilized by sodium dodecyl sulfate solution, was found to be
      3.50+/-0.04 10(-2) cm/s for argon and 3.18+/-0.07 10(-4) cm/s for NH(3). The
      permeability value for the inert gas is in good agreement with data obtained by
      the diminishing-bubble method. When the number of films increases, the
      permeability decreases considerably as a result of cumulative film resistance
      effects. We also developed a simple phenomenological model based upon a
      combination of gas kinetic and energy barrier concepts to interpret our data.
      This model takes into account gas solubility and the effects of salinity, which
      have seemingly been ignored in previous models. The predicted film permeability
      decreases sharply with increase surfactant concentration, indicating the
      occurrence of higher adsorption and increasingly compact surfactant layers.

PMID- 16290553
TI  - Effect of interactions between the adsorbed species on the properties of single
      and mixed-surfactant monolayers at the air/water interface.
AB  - Experimental data on surface tension available from the literature and generated
      in the present study are analyzed to estimate the applicability of adsorption
      models, based on the Frumkin equation, to nonionic and ionic surfactants and
      their mixtures. Optimization programs based on the least-squares method in media
      of Delphi V and Pascal VII are used. The effect of interactions between the
      adsorbed species on surface tension is considered in all cases. The results are
      compared to those obtained with the simpler Szyszkowski equation, employed in
      numerous studies of nonionic surfactants, when interactions are neglected. Cases
      where the Frumkin model can be successfully employed with ionic surfactants and
      mixtures are presented and the conditions of its applicability are analyzed.
      Related characteristic quantities (maximum adsorption, standard free energy of
      surfactant adsorption, energy of interaction between adsorbed species, standard
      free energy of counterion adsorption, degree of coverage by surfactant/counterion
      associates) are established as a function of: The properties of an adsorption
      layer from a mixture of nonionic and ionic surface-active species are compared to
      those of the single surfactants.

PMID- 16290554
TI  - Effect of denaturation by preheating on the foam fractionation behavior of
      ovalbumin.
AB  - Ovalbumin is a globular protein. When it is denatured, it can produce molecular
      species with different conformational states, each of which has different
      adsorption properties at a gas-liquid interface. Such changes in adsorption can
      then affect the foaming behaviors of ovalbumin. Results of semi-batch foam
      fractionation of both native and denatured ovalbumin aqueous solutions are
      reported in this paper, along with possible relationships between denaturation
      and foam fractionation outcomes, such as the enrichment ratio and mass recovery.
      Bubble size and foam stability are determined in the experiments to show the
      effect of denaturation on these measured parameters in this system. The
      relationships between the bubble size, void fraction, and ovalbumin enrichment
      are also reported to reflect the effect of the presence of denatured species.

PMID- 16290555
TI  - Physicochemical properties of quaternized poly(amidoamine) dendrimers with alkyl
      groups and of their mixtures with sodium dodecyl sulfate.
AB  - The physicochemical properties of quaternized poly(amidoamine) dendrimers
      (generation 4) with methyl or octyl groups and of their mixtures with sodium
      dodecyl sulfate (SDS) in aqueous solutions have been investigated using several
      techniques including surface tension, fluorescence of pyrene, and dynamic light
      scattering. In the single systems of the dendrimers, the dendrimer with octyl
      groups shows lower surface tension and lower micropolarity than the dendrimer
      with methyl groups. The hydrodynamic radii of two quaternized poly(amidoamine)
      dendrimers are considerably large, indicating the formation of aggregates. In the
      mixed systems of quaternized poly(amidoamine) dendrimers and SDS, the dendrimer
      with octyl groups-SDS mixed system shows very low surface tension and low
      micropolarity even in the presence of extremely low SDS concentration compared to
      those of the dendrimer with methyl groups-SDS mixed system. Maximum turbidity for
      both systems is observed at around the mixed molar ratio of dendrimer:SDS=1:1.5
      where distinct changes have also been confirmed by surface tension, fluorescence
      of pyrene, and electrical conductivity measurements.

PMID- 16290556
TI  - Electrophoretic mobility of a spherical colloidal particle in a salt-free medium.
AB  - A general expression as well as approximate expressions are derived for the
      electrophoretic mobility of dilute spherical colloidal particles in a salt-free
      medium containing only counter ions. It is shown that there is a certain critical
      value of the particle surface charge. When the particle surface charge is lower
      than the critical value, the electrophoretic mobility is proportional to the
      particle surface charge or the particle zeta potential, following Huckel's
      formula. When the particle surface charge is higher than the critical value, the
      electrophoretic mobility becomes independent of the particle surface charge. This
      is due to the effect of counter ion condensation in the vicinity of the particle
      surface.

PMID- 16290557
TI  - The interplay of diffusional and electrophoretic transport mechanisms of charged
      solutes in the liquid film surrounding charged nonporous adsorbent particles
      employed in finite bath adsorption systems.
AB  - A model that describes the diffusive and electrophoretic mass transport of the
      cation and anion species of a buffer electrolyte and of a charged adsorbate in
      the liquid film surrounding nonporous adsorbent particles in a finite bath
      adsorption system, in which adsorption of the charged adsorbate onto the charged
      surface of the nonporous particles occurs, is constructed and solved. The dynamic
      behavior of the mechanisms of this model explicitly demonstrates (a) the
      interplay between the diffusive and electrophoretic molar fluxes of the charged
      adsorbate and of the species of the buffer electrolyte in the liquid film
      surrounding the nonporous adsorbent particles, (b) the significant effect that
      the functioning of the electrical double layer has on the transport of the
      charged species and on the adsorption of the charged adsorbate, and (c) the
      substantial effect that the dynamic behavior of the surface charge density has on
      the functioning of the electrical double layer. It is found that at equilibrium,
      the value of the concentration of the charged adsorbate in the fluid layer
      adjacent to the surface of the adsorbent particles is significantly greater than
      the value of the concentration of the adsorbate in the finite bath, while, of
      course, the net molar flux of the charged adsorbate in the liquid film is equal
      to zero at equilibrium. This result is very different than that obtained from the
      conventional model that is currently used to describe the transport of a charged
      adsorbate in the liquid film for systems involving the adsorption of a charged
      adsorbate onto the charged surface of nonporous adsorbent particles; the
      conventional model (i) does not consider the existence of an electrical double
      layer, (ii) assumes that the transport of the charged adsorbate occurs only by
      diffusion in the liquid film, and (iii) causes at equilibrium the value of the
      charged adsorbate in the liquid layer adjacent to the surface of the particles to
      become equal to the value of the concentration of the charged adsorbate in the
      liquid of the finite bath. Furthermore, it was found that a maximum can occur in
      the dynamic behavior of the concentration of the adsorbate in the adsorbed phase
      when the value of the free molecular diffusion coefficient of the adsorbate is
      relatively large, because the increased magnitude of the synergistic interplay
      between the diffusive and electrophoretic molar fluxes of the adsorbate in the
      liquid film allows the adsorbate to accumulate (to be entrapped) in the liquid
      layer adjacent to the surface of the adsorbent particles faster than the
      concentrations of the electrolyte species, whose net molar fluxes are
      significantly hindered due to their opposing diffusive and electrophoretic molar
      fluxes, can adjust to account for the change in the surface charge density of the
      particles that arises from the adsorption of the charged adsorbate. The results
      presented in this work also have significant implications in finite bath
      adsorption systems involving the adsorption of a charged adsorbate onto the
      surface of the pores of charged porous adsorbent particles, because the diffusion
      and the electrophoretic migration of the charged solutes (cations, anions, and
      charged adsorbate) in the pores of the adsorbent particles will depend on the
      dynamic concentration profiles of the charged solutes in the liquid film
      surrounding the charged porous adsorbent particles. The results of the present
      work are also used to illustrate how the functioning of the electrical double
      layer could contribute to the development of inner radial humps (concentration
      rings) in the concentration of the adsorbate in the adsorbed phase of charged
      porous adsorbent particles.

PMID- 16290558
TI  - Surface characterization of recycled tire rubber to be used in cement paste
      matrix.
AB  - The surface modification of tire rubber after treatment with saturated NaOH
      aqueous solution was investigated by HATR infrared analysis, potentiometric
      titration, and contact angle measurements. Infrared analysis of the powdered
      treated rubber showed a decrease in absorption at 1540, 1450, and 1395 cm(-1).
      This decrease is attributed to the removal of zinc stearate, an additive present
      in tire formulations that often migrates and diffuses to the surface, resulting
      in poor adhesion between the rubber and other materials. The potentiometric
      titration of the suspension of powdered rubber in 0.1 M NaCl showed that more
      hydrochloric acid was consumed by the untreated rubber, most likely a result of
      the hyrdrolysis of the zinc stearate to the organic acid. Contact angles of flat
      tire pieces showed an homogeneity enhancement of the treated rubber surface. The
      decrease of the zinc stearate on the treated rubber surface explains the
      improvement in the adhesion of this material to the cement matrix, observed in a
      previous research. The promising results of this study are a starting point for
      future research on incorporating rubber particles into cementitious materials as
      a means of successfully utilizing the vast amounts of tire waste currently in
      landfills.

PMID- 16290559
TI  - Transient analysis of electroosmotic flow in a slit microchannel.
AB  - The transient aspects of electroosmotic flow in a slit microchannel are studied.
      Exact solutions for the electrical potential profile and the transient
      electroosmotic flow field are obtained by solving the complete Poisson-Boltzmann
      equation and the Navier-Stokes equation under an analytical approximation for the
      hyperbolic sine function. The characteristics of the transient electroosmotic
      flow are discussed under influences of the electric double layer and the
      geometric size of the microchannel.

PMID- 16290563
TI  - Two independent routes to synthesize identical silicas by grafting ethylenimine
      or 2-aminoethanethiol, their cation adsorbing abilities, and thermodynamic data.
AB  - The same grafted silica gel surface was obtained through two distinct procedures:
      (i) by immobilization of the compound 2-aminoethanethiol on precursor 3
      chloropropylsilylsilica gel in a heterogeneous method, and (ii) by reacting
      ethylenimine with 3-mercaptopropyltrimethoxysilane to give a new silylating
      agent, which was anchored on the silica gel in a homogenous method. The first
      anchored surface gave 0.70 mmol g(-1) of molecules covalently bonded per gram of
      silica. This value contrasts to that obtained with the homogeneous conditions,
      with 1.74 mmol of pendant groups per gram of silica. Both organofunctionalized
      surfaces have the ability to adsorb divalent cations from aqueous nitrate
      solution. The adsorption was performed using a batchwise process and the maximum
      adsorption capacity followed the sequence Cu>Ni>Co and Ni>Cu>Co for surfaces
      prepared by the homogeneous and heterogeneous methods, respectively. Through
      calorimetric titrations, the thermodynamic values of cation-basic center
      interactions were obtained. Exothermic enthalpy results were obtained for all
      interactive processes. The calculated free Gibbs energy is in agreement with the
      spontaneity of the reactions and the positive entropy values for all reactions
      are favorable for this system.

PMID- 16290560
TI  - Viscosity of hard sphere suspensions.
AB  - A simple functional representation of the concentration dependence of the low
      shear viscosity eta of hard sphere suspensions is proposed. The representation,
      which agrees with published literature at all volume fractions phi, has a
      hitherto-unremarked transition in its functional form at phi approximately 0.42
      identical with phi(t). phi(t) is definitely less than the volume fraction 0.49 of
      the hard sphere melting transition.

PMID- 16290564
TI  - Th uptake on montmorillonite: a powder and polarized extended X-ray absorption
      fine structure (EXAFS) study.
AB  - The uptake process of Th(IV) onto montmorillonite was studied using powder and
      polarized-EXAFS (P-EXAFS) spectroscopy. Sorption samples were prepared in 0.1 M
      NaClO(4) solutions either undersaturated (pH 2 and 3, [Th](initial): 2.7x10(-6)
      to 4x10(-4) M) or supersatured (pH 5, [Th](initial): 4.3x10(-5) to 4x10(-4) M)
      with respect to amorphous ThO(2). Th loading varied between 1-157 micromol/g at
      pH 3 and 14-166 micromol/g at pH 5 and equaled 41 micromol/g at pH 2. At pH 5 and
      high surface loading the EXAFS spectrum resembled that of amorphous Th(OH)(4),
      suggesting the precipitation of a Th hydrous hydroxide. At low and intermediate
      surface coverage two O coordination shells at approximately 2.24 and
      approximately 2.48 A, and one Si shell at 3.81-3.88 A, were systematically
      observed regardless of pH. The formation of Th nucleation products and Th-Si
      solution complexes and the sorption of Th on a silica precipitate were excluded
      from the EXAFS spectra analysis and solution chemistry. In these conditions, Th
      was shown to bond the montmorillonite surface by sharing double corners with Si
      tetrahedra. This structural interpretation is consistent with surface coverage
      calculations which showed that the edge sites were saturated in the two highest
      concentrated samples (34 and 157 micromol/g) at pH 3.

PMID- 16290565
TI  - Adsorption of sulfate and copper(II) on goethite in relation to the changes of
      zeta potentials.
AB  - The amount of adsorption of sulfate and Cu(II) from single- and binary-adsorbate
      systems on goethite were measured. All experiments were carried out with and
      without supporting electrolyte (0.01 M NaNO(3)) as a function of equilibrium pH
      (2 - 7), adsorbate concentration (0.21 - 1.57 mM), and temperature (15 - 35
      degrees C). At a given equilibrium pH, it was shown that the adsorption isotherms
      of single sulfate, rather than Cu(II), could be well described by the Langmuir
      equation. The isosteric enthalpy of sulfate adsorption was also evaluated. In
      contrast to a single-adsorbate system, the adsorption of Cu(II) was enhanced and
      that of sulfate was inhibited in binary adsorbate systems under the conditions
      studied. Finally, the changes in zeta potentials of the goethite suspensions with
      solution pH before and after adsorption were measured, which could be
      macroscopically related to the amount of sulfate adsorption even in binary
      adsorbate systems.

PMID- 16290566
TI  - Hybrid monte carlo method for simulation of two-component aerosol coagulation and
      phase segregation.
AB  - The paper presents the development of a hybrid Monte Carlo (MC) method for the
      simulation of the simultaneous coagulation and phase segregation of an immiscible
      two-component binary aerosol. The model is intended to qualitatively model our
      prior studies of the synthesis of mixed metal oxides for which phase-segregated
      domains have been observed in molten nanodroplets. In our previous works (J.
      Aerosol Sci.32, 1479 (2001); Chem. Eng. Sci.56, 5763 (2001); submitted for
      publication) we developed sectional and monodisperse models where the internal
      state of the aerosol particles was described. These methods have certain
      limitations and it is difficult to include additional physical effects into the
      framework. Our new approach combines both constant volume and constant number
      Monte Carlo methods. Similar to our previous models, we assume that the phase
      segregation is kinetically controlled. The MC approach allows us to compute the
      mean number of enclosures (minor phase) per droplet, average enclosure volume,
      and the width of the enclosure size distribution. The results show that
      asymptotic behavior of enclosure distribution exists that is independent of
      initial conditions, which is very close to the continuum self-preserving
      distribution. Temperature is a key parameter because it allows for a significant
      change in the internal transport rate within each droplet. In particular,
      increasing the temperature significantly enhances the Brownian coagulation rate
      and lowers the number of enclosures per droplet. As a result, the MC results
      indicate that the growth of the minor phase can be moderated quite dramatically
      by small changes in system temperature. These results serve to illustrate the
      utility of this synthesis approach to the controlled growth of nanoparticles
      through the use of a majority matrix to slow down the encounter frequency of the
      minor phase and therefore its particle size.

PMID- 16290567
TI  - Zeta potentials and yield stresses of silica suspensions in concentrated
      monovalent electrolytes: isoelectric point shift and additional attraction.
AB  - The zeta potentials and yield stresses of silica suspensions were measured over a
      wide range of monovalent electrolyte concentrations. The counterions investigated
      were Li(+), Na(+), K(+), and Cs(+), while the co-ion was always Cl(-). The poorly
      hydrated ions (Cs(+) and K(+)) adsorb in greater quantity to the silica surface
      than the well-hydrated ions (Li(+) and Na(+)) and produce lower magnitude
      negative zeta potentials at high pH. At high electrolyte concentrations and at
      low pH the poorly hydrated counterions adsorb in great enough quantity to reverse
      the sign of the zeta potential from negative to positive. This specific
      adsorption of counterions shifts the iep to higher values. The shift in the iep
      is directly related to the hydration of the counterion with the least hydrated
      ions creating the greatest iep shift. The yield stresses of silica suspensions at
      high pH were found to increase in the order Li(+)<Na(+)<K(+)<Cs(+). The magnitude
      of the yield stress correlates with the amount of adsorbed ions; i.e., the
      greatest yield stresses are observed with the least hydrated ions. The yield
      stresses measured at high pH with high salt concentrations are greater than can
      be accounted for with just van der Waals attraction. An attractive ion-ion
      correlation force is presumed responsible for the additional attraction necessary
      to explain the observed results.

PMID- 16290568
TI  - Corrected Debye-Huckel analysis of surface complexation. II. A theory of surface
      charging.
AB  - A theory of surface charging of colloidal particles suspended in an electrolyte
      solution is presented. The charging at the particle surface is assumed to
      originate from the adsorption and desorption of protons and is therefore strongly
      dependent on the acidity of the solution. The surface binding of protons occurs
      locally at sites of occupancy zero or one that are described by a binding energy
      u(0) and a three-dimensional vibration of frequency nu. The diffuse screening of
      ions at the surface is described by the corrected Debye-Huckel analysis assuming
      linear response. The model contains a capacitor layer close to the charged
      surface and the finite size of the electrolyte ions is taken into account. The
      theory has been applied to titrated surface charge data on goethite (alpha-FeOOH)
      at NaClO(4) background concentrations ranging from 0.01 to 1.0 M. The protonation
      mechanism used in the modeling of these data corresponds to the 1-pK approach. A
      very good description of the experimental data was obtained at the highest ionic
      strength. Close to the pH(pzc) the theory also gave a good description at lower
      ionic strengths. However, at low salt concentrations and pH values far away from
      the pH(pzc) the electrostatic potential outside the capacitor layer becomes so
      high that nonlinear electrostatic effects become important and the theory
      therefore underestimates the surface charge. These results were compared with
      model calculations obtained using existing surface complexation models.

PMID- 16290569
TI  - Interfacial adhesion and microfailure modes of electrodeposited carbon
      fiber/epoxy-PEI composites by microdroplet and surface wettability tests.
AB  - Interfacial properties and microfailure modes of electrodeposition (ED)-treated
      carbon fiber-reinforced polyetherimide (PEI) toughened epoxy composite were
      investigated using microdroplet test and the measurement of surface wettability.
      ED was performed to improve the interfacial shear strength (IFSS). As PEI content
      increased, IFSS increased due to enhanced toughness and plastic deformation of
      PEI. In the untreated case, IFSS increased with adding PEI content, and the IFSS
      of the pure PEI matrix showed the highest. On the other hand, for the ED-treated
      case IFSS increased with PEI content with rather low improvement rate. In the
      untreated case, neat epoxy resin appeared brittle microfailure mode, whereas the
      pure PEI matrix exhibited a more likely ductile microfailure mode. In the ED
      treated case, neat epoxy exhibited a more ductile fracture than that of the
      untreated case. Critical surface tension and polar surface free energy of ED
      treated carbon fiber was higher than those of the untreated fiber. The work of
      adhesion between fiber and matrix was not directly proportional to IFSS for both
      the untreated and ED-treated cases. The matrix toughness might contribute to IFSS
      more likely than the surface wettability. Interfacial properties of the epoxy-PEI
      composite can be affected efficiently by both the control of matrix toughness and
      ED treatment.

PMID- 16290570
TI  - Calculations of van der Waals forces in 2-dimensionally anisotropic materials and
      its application to carbon black.
AB  - We present calculations of the van der Waals force for carbon black dispersions
      in both aqueous and nonaqueous media using Lifshitz theory. The microstructure
      and composition of carbon black are complex, but an initial approximation to the
      shell-like microstructure of carbon black allows the local interaction of carbon
      black particles to be approximated as oriented domains of graphite. The
      dielectric spectra for graphite, which has a 2-dimensional anisotropy due to its
      the layered microstructure, is required for the Lifshitz theory van der Waals
      force calculations. The anisotropic dielectric spectra of graphite (which behaves
      as a semiconductor) was constructed by modeling the conduction or free charge
      response separately from the polarization or bound charge response. The free
      charge response was modeled using the Drude model, while the dielectric spectra
      for the bound charge response was constructed from the spectroscopic data
      directly according to the Kramers-Kronig relation for the dielectric function,
      epsilon(omega). The expressions for calculating the fully retarded van der Waals
      force for half spaces with 2-dimensional dielectric anisotropy were derived as
      well as. The construction for the dielectric spectra of polystyrene from recent
      spectroscopic data from the literature according to the method outlined in
      (Dagastine, R. R., Prieve, D. C., and White, L. R., J. Colloid Interface Sci.231,
      351 (2000)) is also presented.

PMID- 16290571
TI  - The determination of thickness and surface mass density of mesothick
      immunoprecipitate layers by null ellipsometry and protein 125iodine labeling.
AB  - The aim of the present study was to ellipsometrically determine the thickness and
      surface mass density in air for up to 110-nm-thick organic layers made of
      alternatingly deposited layers of HSA and polyclonal anti-HSA on hydrophobic
      silicon. The ellipsometrically determined thickness was compared to that obtained
      by AFM and the deposited surface mass density calibrated with (125)I-labeled
      proteins. The results indicate a good agreement in protein layer thickness
      between AFM and ellipsometry when the protein film refractive index N(film)=1.5
      0i, although then the calculated surface mass density from the ellipsometry data
      became grossly overestimated by the Cuypers one-component formula. A good
      agreement in the surface mass density was obtained when the M/A ratio in this
      formula was lowered from 4.14 to 2.35. This approach indicates a convenient means
      of determining the refractive indices and surface mass densities of mesothick
      organic layers proteins on solid supports.

PMID- 16290572
TI  - Multilayer films from phenolic resin-sodium dodecyl sulfate complex and
      polycations.
AB  - Novel multilayer ultrathin films of PR-SDS-PC were fabricated by employing the
      complex of phenolic resin (PR) and sodium dodecyl sulfate (SDS) as a "complex
      polyanion" and various polycations (PCs). The resulting films were etched quickly
      when being immersed in polar organic solvents due to the weak hydrophobic
      interaction between PR and SDS. By employing the photosensitive diazo resin (DR)
      as PC, the stability of the PR-SDS-DR film increases significantly after UV
      irradiation, because a covalent crosslinking structure forms in the film.

PMID- 16290573
TI  - Modeling nucleation and coagulation modes in the formation of particulate matter
      inside a turbulent exhaust plume of a diesel engine.
AB  - This paper presents the results from a study that is aimed at predicting the
      nucleation, coagulation, and dynamics of particulate matter (PM) emissions from
      on-road heavy-duty diesel vehicles. The PM concentration is predicted from the
      composition of fuel, and operating and ambient conditions. A numerical algorithm
      for simultaneously solving the coagulation, condensation, and nucleation
      equations is developed. The effect of relative humidity on the nucleation rate
      and the nucleus size is also discussed. In addition, the effect of the ambient
      air dilution on PM size distribution is numerically predicted for a diesel
      powered truck operating in a controlled environment at NASA Langley wind-tunnel
      facility. The particle size distribution and concentration are measured at four
      different locations in a turbulent plume from the diesel exhaust in the tunnel,
      and an excellent agreement between the measured and predicted PM concentration
      values at these locations inside the tunnel is observed.

PMID- 16290574
TI  - Effect of mordenite dealumination on the structure of encapsulated molybdenum
      catalysts.
AB  - A series of dealuminated mordenites treated under various conditions of acid
      leaching was impregnated in an aqueous solution of ammonium heptamolybdate to
      achieve a loading of 12 wt% Mo. These samples were characterized by XRD, UV-DRS,
      N(2) adsorption, TGA, and FTIR techniques. Special attention was given to the far
      IR measurements and IR study of surface hydroxyl groups before and after
      dealumination. A polymolybdate species was recognized by the appearance of bands
      at 344, 319, and 236 (229) cm(-1) due to the vibrational modes of delta(Mo-O) and
      delta(Mo-O-Mo), respectively. The disappearance of the 236 cm(-1) band as well as
      that at 344 cm(-1) in favor of the 319 cm(-1) band, with the dealumination, was
      related to the high dispersion of Mo species in the produced mesopore surface
      assessed by the N(2) adsorption at 77 K. No bands due to bulk MoO(3) were
      detected from the IR and XRD results. A strong interaction between Mo species and
      dealuminated mordenite surfaces (OH groups) was recognized by a decrease in
      intensity and a marked shift of the band at 3745 to 3727 cm(-1) as well as the
      appearance of a new band at 3668 cm(-1). The latter band was produced by the
      interaction of the framework Al-OH with Mo species. The BET surface areas of Mo
      dealuminated mordenite samples were higher than the corresponding Mo-free ones.
      The diffuse reflectance measurements suggested that Mo cations are predominantly
      present as an octahedrally coordinated Mo(6+), along with some tetrahedral
      Mo(6+). New spectral features as a consequence of dealumination events in the far
      IR range were evaluated and discussed.

PMID- 16290575
TI  - Influence of carbonates on the surface charge of a natural solid.
AB  - Carbonates are the predominating species in natural chemical processes. Thus,
      understanding the reactions that occur on their surfaces is very important. The
      aim of this study was to determine the influence of carbonates on the surface
      charge of a natural soil sample. First, surface properties of a synthesized
      calcite were determined using a simplified surface speciation model correlated to
      potentiometric titrations, and then intrinsic acidity constants and pH(znpc) (pH
      where protonic surface charge is equal to 0) were studied for solids with
      different percentages of calcite. A strong influence on surface properties of the
      solids was evidenced even for small additional quantities of calcite.

PMID- 16290576
TI  - A time-resolved laser fluorescence spectroscopy (TRLFS) study of the interaction
      of trivalent actinides (Cm(III)) with calcite.
AB  - Cm(III) interaction with calcite was investigated by time-resolved laser
      fluorescence spectroscopy (TRLFS) in the trace concentration range. Two different
      Cm(III)/calcite sorption species were found. The first Cm(III) sorption species
      consists of a curium ion bonded onto the calcite surface. The second Cm(III)
      sorption species has lost its complete hydration sphere and is incorporated into
      the calcite bulk structure. The Cm(III)/calcite complexes are characterized by
      their emission spectra (peak maxima at 607.5 and 618.0 nm) and their fluorescence
      emission lifetimes (314+/-6 and 1302+/-75 micros).

PMID- 16290577
TI  - Structural and energetic characteristics of silicas modified by organosilicon
      compounds.
AB  - Silica gels Davisil 633 and 643, and fumed silica Cab-O-Sil HS-5 with grafted 3
      aminopropyl dimethylsilyl (APDMS), butyl dimethylsilyl (BDMS), octadecyl
      dimethylsilyl (ODDMS), and trimethylsilyl (TMS) groups of different
      concentrations were studied using the nitrogen adsorption method. Changes in the
      textural and energetic characteristics of modified silicas depend on features of
      the oxide matrices and grafted OSC.

PMID- 16290578
TI  - Stable drop shapes under disjoining pressure. I. A hierarchical approach and
      application.
AB  - The contact line region as affected by the disjoining pressure has been analyzed
      under the assumption that it can sustain only two types of profiles. Disjoining
      pressure represents the extra potential in thin films that always exists in the
      contact angle region where a liquid drop or a wedge thins to meet the solid
      substrate and in turn affects the contact angle as well as the film profile. It
      is shown here that the integration of the augmented Young-Laplace equation to
      yield the above types of drop profiles under the action of disjoining pressure
      leads to the usual conditions of equilibrium as well as the condition of
      stability in the same analysis. Other inequality constraints are obtained where
      the stability condition does not apply. The fact that stability condition
      coexists with the conditions of equilibrium is pursued to show in one case that
      the stability modifies half of the predicted outcomes in the drop shapes. In
      addition, exceptions to the rule are found, which are physically meaningful, and
      a scale-dependent equilibrium is reported for the first time.

PMID- 16290579
TI  - Stable drop shapes under disjoining pressure. II. Multiplicity and stability.
AB  - The stability of the contact line region as affected by the disjoining pressure
      has been analyzed by solving the augmented Young-Laplace equation. Because of the
      results in Part I (Zhang, X., Neogi, P., and Ybarra, R. M., J. Colloid Interface
      Sci.), we have concentrated on obtaining multiple solutions for the same set of
      conditions. As many as five solutions were obtained: drops that end in a thin
      film with uniform thickness and where the film shape oscillates, drops that end
      with microscopic contact angles, as well as uniform thin films of two different
      thicknesses. The results of linear stability analysis were used to show that most
      cases were unstable to infinitesimal disturbances. Only two stable drop shapes
      for the particular disjoining pressure investigated are stable, a thin film of
      constant thickness and a thin drop that ends in a film of same thickness. Both
      multiplicity and stability have been discussed here for the first time and shed
      considerable light on the role of the attractive and repulsive forces.

PMID- 16290580
TI  - Empirical equations for meniscus depression by particle attachment.
AB  - In this paper the problem of calculating the depression of the gas-liquid
      meniscus by the particle attachment was solved. The analytical approximate
      equations obtained for small and large radii, r(tpc), of the three-phase contact
      were analyzed and compared to the available numerical results. The Derjaguin
      equation for small r(tpc) and the analytical results for large r(tpc) are
      accurate for r(tpc)/L< or =0.2 and r(tpc)/L> or =2, respectively, where L is the
      capillary length. For the meniscus depression with r(tpc)/L from 0.2 to 2, the
      empirical equations were obtained based on the asymptotic analysis of the
      analytical approximate solutions. The empirical numerical constants were obtained
      by fitting to the exact numerical results. The empirical equations together with
      the analytical approximate equations provide the accurate predictions for the
      meniscus depression for the whole range of the radius of the three-phase contact
      and are expected to be useful for modeling the detachment interaction in the
      flotation separation processes.

PMID- 16290581
TI  - A molecular modeling study of pentanol solubilized in a sodium octanoate micelle.
AB  - In order to study the structural and dynamical aspects of the solubilization
      process of pentanol within a sodium octanoate micelle a molecular dynamics
      simulation is presented. In this initial study we discuss the results and
      detailed insights into the interactions between sodium octanoate, pentanol, and
      water. The total micellar radius and the hydrophobic core radius were determined.
      The calculated values are in fairly good agreement with experimental results. In
      contrast to pure sodium octanoate micelles the aggregate with dissolved pentanol
      attained a more spherical shape related to the time interval of the simulation.
      It is clear that the results of a molecular dynamics computer simulation are
      always limited by its total length and the total time used for data analysis.
      Nevertheless, from our simulation study it turned out that a part of the pentanol
      hydroxyl groups were located within the micellar core and some alcohol molecules
      were also observed at the surface region of the micelle. The corresponding
      partition coefficient was calculated and agreed well with the experiment. The
      evaluated radial distribution functions of the sodium ions, the octanoate
      oxygens, and the hydroxyl hydrogens reveal details of the interface region of the
      micelle and the bulk phase. Additionally, it was possible to calculate the trans
      to-gauche ratios of the alkyl chains and to compare these results with the
      simulation of a pure octanoate micelle.

PMID- 16290582
TI  - Parametric equations of the theory of formation of spherical micelles.
AB  - Using the notion of aggregation work, we construct a system of differential
      equations for the aggregation number of micelles which is a function of the
      parameters of micellization (parametric equations). There are explicit solutions
      for two important models of spherical micelles. Based on these solutions, we
      obtain an analytical expression for the equilibrium concentration of surfactant
      monomers and consequently for the whole spectrum of equilibrium concentrations of
      molecular aggregates in this framework. Accuracy of these expressions is
      discussed, and they are applied to an example of micelles formed by sodium
      dodecyl sulfate.

PMID- 16290584
TI  - Direct cryogenic-temperature transmission electron microscopy imaging of
      phospholipid aggregates in soybean oil.
AB  - Cryogenic-temperature transmission electron microscopy (cryo-TEM) was fine-tuned
      to make it applicable to the study of a natural oil-based system. While liquid
      ethane, the cryogen of choice for specimen preparation, was found to dissolve the
      oil, we observed that the triglycerides found in many natural oils serve as
      cryoprotectants that allow vitrification of such oil systems in liquid nitrogen,
      a cryogen that provides relatively low cooling rates. Using the modified
      technique combined with digital imaging by a cooled CCD camera, we were able to
      directly visualize inverse micellar and liquid-crystalline aggregates formed in
      the soybean oil/soybean phospholipids/water/hexane system, which is commercially
      important in soybean oil processing. The method developed here should be widely
      applicable to other organic solvent-based systems.

PMID- 16290583
TI  - Hydrotrope-induced autocatalysis in the biphasic alkaline hydrolysis of aromatic
      esters.
AB  - The alkaline hydrolysis of aromatic esters exhibits autocatalytic kinetics when
      performed under two-phase conditions without any mixing solvent. The molecular
      structures of such aromatic esters determine whether the autocatalysis occurs or
      not. It has been established that enhancing the solubility of the hydrophobic
      ester in water by the hydrotropic salts yielded by the hydrolysis itself
      accelerates the apparent reaction rate. By kinetically independent measurements,
      the solubilization process of the ester was verified to be the rate-determining
      step. It has been observed that the solubilization process can be influenced by
      factors such as the initial addition of hydrotropic salt, the volumetric ratio of
      the oil/aqueous phase, and the concentration of alkali.

PMID- 16290585
TI  - Studies of synergism/antagonism for lowering dynamic interfacial tensions in
      surfactant/alkali/acidic oil systems. 1. Synergism/Antagonism in surfactant/model
      oil systems.
AB  - Experimental studies are conducted in order to elucidate the mechanisms
      responsible for synergism/antagonism for lowering dynamic interfacial tension in
      model oil/surfactant/brine systems. A well-defined model oil is selected for
      controlled design of experiments, thus enhancing verification of known and
      unknown mechanisms. The systems examined contain model oils and two petroleum
      sulfonate solutions. The influence of additives in oil phase, such as carboxylic
      acids with different chain length, n-octadecanol, and oil soluble surfactant SP
      60, on the equivalent alkane carbon number (EACN) values has been examined. The
      interfacial tensions of different model oils with different EACN values against
      surfactant solutions with different n(min) values have also been obtained. We
      find that antagonism has been observed when EACN/n(min) value is far from unity
      by adding organic components, while synergism has been observed when EACN/n(min)
      value is close to unity. The results present here suggest that organic additives
      in oil phase controlled interfacial tension by changing the partition of
      surfactants in oil phase, aqueous phase, and interface.

PMID- 16290586
TI  - Liquid drainage in single plateau borders of foam.
AB  - This paper reports on an investigation of the influence of the interfacial shear
      viscosity on the liquid drainage in single Plateau borders of foam. The
      simplified Navier-Stokes equation governing the liquid flow is solved for the
      liquid velocity by the numerical computational method. The numerical results show
      significant influence of the interfacial shear viscosity on the liquid velocity
      in the Plateau border. Comparison of the numerical results for the average
      velocity over the cross-section area of the Plateau border to the available
      analytical solution shows that the available analytical solution underestimates
      the average velocity. New, simple yet accurate correlations for the dependence of
      the average velocity on the radius of the cross section of the Plateau border,
      the pressure gradient, and the interfacial shear viscosity are obtained using the
      asymptotic analysis and the numerical data.

PMID- 16290587
TI  - Mixed micelles of polyethylene glycol (23) lauryl ether with ionic surfactants
      studied by proton 1D and 2D NMR.
AB  - (1)H NMR chemical shift, spin-lattice relaxation time, spin-spin relaxation time,
      self-diffusion coefficient, and two-dimensional nuclear Overhauser enhancement
      (2D NOESY) measurements have been used to study the nonionic-ionic surfactant
      mixed micelles. Cetyl trimethyl ammonium bromide (CTAB) and sodium dodecyl
      sulfate (SDS) were used as the ionic surfactants and polyethylene glycol (23)
      lauryl ether (Brij-35) as the nonionic surfactant. The two systems are both with
      varying molar ratios of CTAB/Brij-35 (C/B) and SDS/Brij-35 (S/B) ranging from 0.5
      to 2, respectively, at a constant concentration of 6 mM for Brij-35 in aqueous
      solutions. Results give information about the relative arrangement of the
      surfactant molecules in the mixed micelles. In the former system, the trimethyl
      groups attached to the polar heads of the CTAB molecules are located between the
      first oxy-ethylene groups next to the hydrophobic chains of Brij-35 molecules.
      These oxy-ethylene groups gradually move outward from the hydrophobic core of the
      mixed micelle with an increase in C/B in the mixed solution. In contrast to the
      case of the CTAB/Triton X-100 system, the long flexible hydrophilic poly oxy
      ethylene chains, which are in the exterior part of the mixed micelles, remain
      coiled, but looser, surrounding the hydrophobic core. There is almost no
      variation in conformation of the hydrophilic chains of Brij-35 molecules in the
      mixed micelles of the SDS/Brij-35 system as the S/B increases. The hydrophobic
      chains of both CTAB and SDS are co-aggregated with Brij-35, respectively, in
      their mixed micellar cores.

PMID- 16290588
TI  - Rheological study of the sol-gel transition in silica alkoxides.
AB  - The sol-gel transition of the system tetramethylorthosilicate-water-methanol
      under basic conditions has been studied by rheological measurements. The gelation
      time t(g) has been determined from the measurements of the elastic G' and viscous
      G'' moduli as a function of time at different frequencies according to Winter's
      criterion. At gelation time the frequency dependence of both moduli follows a
      power law with an exponent related to the fractal dimension of the network
      structure. Different initial monomer concentrations, hydrolysis molar ratios, and
      temperatures are studied. The decrease of the gelation time with an increase of
      initial monomer concentration or hydrolysis molar ratio is well-described by a
      power law. An apparent activation energy is deduced from the temperature
      dependence of gelation time.

PMID- 16290589
TI  - Electroosmotic flows with random zeta potential.
AB  - The hydrodynamic problem of electroosmotic flow in a cylindrical capillary with
      random zeta potential is solved in the limit of small Deybe length and low
      Reynolds number. Averages are defined over multiple experiments and the mean
      axial velocity is found to be a plug flow. The variance of the velocity exhibits
      parabolic-like variation across the capillary. Average concentrations of samples
      transported by the flow are approximated by defining an effective diffusivity
      coefficient. Theoretical formulas for the average concentration are supported by
      numerical experiments.

PMID- 16290590
TI  - Admicellar polymerization of styrene on cotton.
AB  - Thin-film coating on cotton by the admicellar polymerization process was
      investigated. In this work, styrene was used as the monomer to coat styrene on
      cotton. The effects of surfactant, styrene, initiator, and electrolyte
      concentrations on the polymerization process were determined. The polystyrene
      film formed was characterized by SEM, FTIR, and GPC. The increase in the
      hydrophobicity of the treated cotton surface was determined by the drop test.
      Results show that polystyrene thin film was successfully formed on cotton,
      resulting in cotton that can resist wetting by a water droplet for longer than 30
      min.

PMID- 16290591
TI  - Synthesis and surface properties of environmentally responsive segmented
      polyurethanes.
AB  - Polyurethanes, containing well-defined assemblies of perfluoro-polyether (PFPE or
      hexafluoropropene oxide oligomer), polydimethylsiloxane (PDMS), and polyethylene
      glycol (PEG) segments, exhibit oleophobic, hydrophobic, and hydrophilic
      properties in response to the polarity of the contacting medium. These polymers
      were prepared by reacting hydroxy(polyethyleneoxy)-propylether-terminated PDMS
      block copolymer (HO-PEG-PDMS-PEG-OH) with 4,4'-methylene-bis(phenylene
      isocyanate) (MDI) in the presence of dibutyltin dilaurate catalyst, followed by
      reaction with 1,2-diol functional PFPE and chain extension with 2,2,3,3
      tetrafluoro-1,4-butanediol (FB). The oleophobic and hydrophobic properties of the
      segmented polyurethanes (SPU) are due to the segregation of PFPE segments at the
      polymer-air interface. Wettability studies revealed that the same surface becomes
      hydrophilic, presumably due to the segregation of the PEG segments at the polymer
      water interface. This hydrophobic-to-hydrophilic transformation of the surface
      prevails not only when the polymer is in contact with liquid water but with water
      vapor as well. The understanding of the reconstruction mechanism of this novel
      family of SPU surfaces would furnish valuable information for various
      applications where dynamic transformation of surface activity is desired.

PMID- 16290593
TI  - Coagulation-flocculation of beech condensate: particles size distribution.
AB  - Beech wood (Fagus sylvatica L.) condensate from a steaming operation was studied.
      The objective of our work was to study the precipitation of these wood extracts
      in presence of calcium ion after autoxidation at basic pH (8). The autoxidation
      was carried out at 250 rpm for 30 min, and flocculation was followed up for 30
      min. An investigation with a laser sizer Mastersizer of Malvern has been done in
      order to study the influence of the agitation on the state of aggregation of the
      condensate. A negative correlation was observed between the mean size of
      particles and the agitation rate. Without stirring, flocculation rapidly occurred
      and the mean size of particles was high. Calcium-induced aggregation of the
      condensate was also found to be reversible toward agitation.

PMID- 16290592
TI  - Dewetting of unreacted epoxy/amine mixtures on silica.
AB  - We employ a direct method, time-of-flight secondary ion mass spectroscopy (ToF
      SIMS), to determine experimentally the chemical compositions of the wetted and
      dewetted regions of an uncured epoxy thin film. Determining the composition of
      the dewetted region indicated the presence of a very thin sublayer of resin in
      what was thought to be a region devoid of resin. The capability of ToF-SIMS to
      probe small 65 x 65 microm(2) areas of the surface has permitted us to directly
      compare the SIMS spectra of the wetted and dewetted regions to the survey spectra
      of the reactants. This may indicate the strength of resin/silica interactions,
      which determine interface formation and properties.

PMID- 16290594
TI  - The simple procedure of the calculation of diffusion coefficient for adsorption
      on spherical and cylindrical adsorbent particles--experimental verification.
AB  - A recently proposed simplified procedure for calculating the effective diffusion
      coefficient (D(e)) for adsorption on spherical and cylindrical adsorbent
      particles is now experimentally verified for adsorption systems: paracetamol
      activated carbon. Adsorption kinetics was measured on nine carbons; for seven of
      them, measurements were taken at three temperatures. Since for adsorption on
      spherical adsorbent particles the approximate methods of D(e) calculation are
      already available in literature, only two systems have been studied, and the
      results of the new procedure are compared with those calculated from previously
      published methods. However, for cylinders the proposed method is the first
      simplification of this kind available in literature, thus, we focus our attention
      on the comparison of the results of the analytical approach with the simplified
      approaches for the systems where an adsorbent possesses cylindrically shaped
      granules. It is shown that for adsorption on spherical as well as on cylindrical
      adsorbent granules the proposed simplification leads to satisfactory results
      that, taking into account an experimental error, are practically the same as
      those obtained from exact time-consuming and mathematically advanced numerical
      fitting procedure. It is also shown that, for the studied carbons, the surface
      diffusion process dominates, and this explains the recently obtained correlation
      between the effective diffusion coefficient and the enthalpy of carbon immersion
      in water.

PMID- 16290596
TI  - Development of a constant surface pressure penetration langmuir balance based on
      axisymmetric drop shape analysis.
AB  - A new constant pressure pendant-drop penetration surface balance has been
      developed combining a pendant-drop surface balance, a rapid-subphase-exchange
      technique, and a fuzzy logic control algorithm. Beside the determination of
      insoluble monolayer compression-expansion isotherms, it allows performance of
      noninvasive kinetic studies of the adsorption of surfactants added to the new
      subphase onto the free surface and of the adsorption/penetration/reaction of the
      former onto/into/with surface layers, respectively. The interfacial pressure pi
      is a fundamental parameter in these studies: by working at constant pi one
      controls the height of the energy barrier to adsorption/penetration and can
      select different regimes and steps of the adsorption/penetration process. In our
      device a solution drop is formed at the tip of a coaxial double capillary,
      connected to a double microinjector. Drop profiles are extracted from digital
      drop micrographs and fitted to the equation of capillarity, yielding pi, the drop
      volume V, and the interfacial area A. pi is varied changing V (and hence A) with
      the microinjector. Control is based on a case-adaptable modulated fuzzy-logic PID
      algorithm able to maintain constant pi (or A) under a wide range of experimental
      conditions. The drop subphase liquid can be exchanged quantitatively by the
      coaxial capillaries. The adsorption/penetration/reaction kinetics at constant pi
      are then studied monitoring A(t), i.e., determining the relative area change
      necessary at each instant to compensate the pressure variation due to the
      interaction of the surfactant in the subsurface with the surface layer. A fully
      Windows-integrated program manages the whole setup. Examples of experimental
      protein adsorption and monolayer penetration kinetics are presented.

PMID- 16290597
TI  - Sensing specific adhesion of liposomal and micellar systems with attached
      carbohydrate recognition structures at lectin surfaces.
AB  - A quartz crystal microbalance was used to investigate the adsorption behavior of
      liposomes and mixed micelles with attached carbohydrate recognition structures at
      lectin-coated quartz plates. With a self-assembly technique, the quartz was
      coated with the lectin Concanavalin A. In a first attempt, liposomes of natural
      soybean PC as well as synthetic POPC, containing 10% reactive N-Glut-PE each,
      were decorated with a mannopyranoside recognition structure to investigate the
      specific adsorption at the lectin-coated quartz surface in dependence on the
      concentration. In a second model, the bile salt sodium cholate was introduced to
      solubilize the mannopyranoside-modified liposomes and to transform them into
      mannopyranoside-modified binary mixed micelles. The adsorption of these micelles
      was further investigated. In a third approach, the adsorption behavior of
      mannopyranoside-modified ternary mixed bile salt-phosphatidylcholine-fatty acid
      micelles was characterized with sodium laurate, palmitate, and oleate as fatty
      acids. The micelles with oleate showed only a small frequency decrease, whereas
      the micelles with laurate and palmitate induced higher frequency changes. A
      dependence on the alkyl chain length could be detected. While the adsorption of
      liposomes containing recognition structures at QCM surfaces is nowadays well
      established, the QCM detection of the adsorption of mixed bile salt micelles,
      transformed from these liposomes by solubilization, is a novel and very promising
      field for the development of innovative colloidal drug delivery systems.

PMID- 16290599
TI  - Chemisorption and thermodynamic data of the interaction between a chelate free
      acidic center with basic groups attached to grafted silicas.
AB  - The molecule 2-aminoethanethiol was added to the grafted silylant agent [(3
      chlorosilylpropyl)trimethoxysilane] (cpts) onto silica gel(triple bond SilCl),
      obtaining a surface (triple bond SilSNH(2)) and giving 0.70 mmol g(-1) of
      nitrogen; the surface of silica was modified with [(3
      mercaptosilylpropyl)trimethoxysilane] (mpts) with surface (triple bond SilSH),
      giving 0.78 mmol g(-1) of sulphur. Both matrices, (triple bond SilSNH(2)) and
      (triple bond SilSH), adsorb copper and cobalt acetylacetonates from ethanolic
      solution. Adsorption, using a batchwise process, showed that copper chelate was
      the most adsorbed. The interactions between the basic centers attached to organic
      chains of these modified silicas with the cations in the chelates Me(acac)(2)
      [M=Cu and Co] were followed through calorimetric titrations. Exothermic enthalpic
      results were obtained for the triple bond SilSNH(2) matrix. The spontaneity of
      these systems was reflected in negative free Gibbs energy and positive from
      entropic values.

PMID- 16290598
TI  - Specific counterion effects on the competitive co-adsorption of polyelectrolytes
      and ionic surfactants.
AB  - Counterions affect not only the bulk and interfacial self-assembly of ionic
      surfactants but also their competitive adsorption with similarly charged
      polyelectrolytes. Here, we explore the specific effects of bromide, chloride, and
      the bulky, somewhat hydrophobic tosylate counterion on the adsorption of
      hexadecyltrimethylammonium surfactants (CTA(+)), the adsorption of polylysine
      (PL), and the co-adsorption of CTA(+) and PL on negatively charged silica
      surfaces. Similar to bulk self-assembly, increasing the micellar binding affinity
      of the counterion from chloride to bromide to tosylate promoted interfacial self
      assembly in the absence of polylysine. During co-adsorption, the presence of the
      polylysine decreased the adsorbed amount of CTA(+) in all cases. Polylysine was
      more effective at hindering CTA(+) adsorption when the surfactant concentration
      was below the critical micelle concentration. Although these systems were
      strongly influenced by persistent nonequilibrium states, it was possible to
      demonstrate that polylysine was able to prevent CTA(+) admicelle formation below
      the cmc only when the thermodynamic driving forces for adsorption of the polymer
      and the surfactant were comparable. Solution compositions where that condition
      was met depended on the identity of the counterion. Below the bulk cmc, CTAT
      adsorption displayed the greatest degree of cooperativity, and it also was the
      most susceptible to hindered adsorption by polylysine.

PMID- 16290600
TI  - Adsorption of heavy metal ions to floc-type biosorbents.
AB  - Adsorption of cadmium and lead ions to floc-type biosorbents was reported in this
      work. Two types of biosorbents containing a marine microalga, Heterosigma
      akashiwo (Hada) Hada, or a purple non-sulfur bacterium, Rhodobacter sphaeroides,
      were prepared. The micro-organisms inactivated by steam sterilization were
      immobilized in casein floc and cross-linked with glutaraldehyde. In the present
      immobilizing method, we obtained the biosorbents comprising as much as 67% of
      micro-organism on a dry-weight basis. Simple metal-binding models were applied to
      explain the adsorption mechanism of bivalent metal ions to the biosorbents. The
      results showed that casein acted as both the immobilizing material and the
      adsorbent material. The adsorption of bivalent metal ions to the biosorbents was
      due to bidentate binding to the acidic sites on casein and monodentate binding to
      the acidic sites on micro-organisms. The metal-binding constants and the binding
      capacities of micro-organisms were scarcely influenced by immobilization.

PMID- 16290602
TI  - Layer-by-layer self-assembled ultrathin multilayer films of lanthanide
      polyoxometalates and poly(allylamine hydrochloride) and their photoluminescent
      properties.
AB  - Ultrathin multilayer films of two lanthanide polyoxometalates (LPOMs),
      K(17)[Eu(P(2)W(17)O(61))(2)] (EPW) and K(13)[Eu(SiW(11)O(39))(2)] (ESW), and
      poly(allylamine hydrochloride) (PAH) have been prepared by layer-by-layer self
      assembly from dilute aqueous solutions. UV-vis spectroscopy and ellipsometry
      respectively show that the absorbance values at characteristic wavelengths and
      the thicknesses of the multilayer films increase linearly with the number of
      LPOM/PAH bilayers, suggesting that the deposition process is linear and highly
      reproducible from layer to layer. Average thicknesses of ca. 3.4 and 2.4 nm were
      determined for the EPW/PAH and ESW/PAH bilayers by ellipsometry, respectively. In
      addition, scanning electron microscopy (SEM) and atomic force microscopy (AFM)
      images provide the surface morphology of the LPOM/PAH films, indicating that the
      film surface is relatively uniform and smooth. The photoluminescent properties of
      these films have also been investigated by fluorescence spectroscopy. The
      LPOM/PAH multilayer film has a good thermal stability as shown by UV-vis, X-ray
      photoelectron, and fluorescence spectra.

PMID- 16290601
TI  - Self-assembly of L-cysteine-copper(II)/copper(I) multilayer thin films on gold.
AB  - Self-assembled multilayer thin films have been prepared on Au substrate by
      alternate surface derivatization with L-cysteine hydrochloride and cupric
      perchlorate. The layer-by-layer structure at each step of multilayer formation
      was investigated by X-ray photoelectron spectroscopy. The measurements indicate
      that there are two structure modes in the multilayers. One is that Cu(2+)
      sandwiches between two amino acid groups. The other one is that Cu(+) is bonded
      through disulfide and thiolate. This process is also confirmed by cyclic
      voltammetry of Cu ion at different self-assembled multilayers. Steps further on
      will lead to repeated multilayer films.

PMID- 16290603
TI  - Interaction of carboxylic acids with chitosan: effect of pK and hydrocarbon chain
      length.
AB  - Sorption of acetic, propionic, butyric, valeric, and isovaleric acid on chitosan
      and cross-linked chitosan was studied in aqueous solutions and water/ethanol
      mixtures. Langmuir, Freundlich, and Redlich-Peterson equations were used to fit
      experimental isotherms of sorption. Correlation between maximum sorption and the
      pK value of every carboxylic acid was found for sorption on chitosan in aqueous
      solutions, while sorption in water/ethanol mixtures was mainly determined by
      structure and the hydrocarbon chain length of the carboxylic acid. Slight
      molecular-sieves effect was found for carboxylic acids sorption on cross-linked
      chitosan.

PMID- 16290604
TI  - Electrophoresis of progesterone particles dispersed in carbohydrate and
      nonelectrolyte solutions.
AB  - Electrophoretic mobilities of progesterone particles dispersed in aqueous
      solutions of D-glucose and urea (concentration range 0.1 to 1 mM) have been
      measured in order to investigate the electrical properties of the interface. Zeta
      potentials have been determined for this purpose. The dependence of Zeta
      potentials on concentration has also been examined. Theory of the electrical
      double layer has been used to explain the results.

PMID- 16290605
TI  - Analysis of the dielectric permittivity of suspensions by means of the
      logarithmic derivative of its real part.
AB  - Measurement of the dielectric permittivity of colloidal suspensions in the
      kilohertz frequency range (the so-called low-frequency dielectric dispersion) is
      a promising tool for the electrokinetic characterization of colloids. However,
      this technique is less used than would be desirable because of the difficulties
      associated with the measurements, the most important of which is the electrode
      polarization (EP). Recently (M. Wubbenhorst and J. Van Turnhout, Dielectrics
      Newsl. November (2000)) a method was proposed that appears capable of separating
      the unwanted electrode effects from the double-layer relaxation that we are
      interested in. The method, based on the logarithmic derivative of raw
      epsilon'(omega) data (epsilon'(omega) is the real part of the permittivity of the
      suspension for a frequency omega of the applied AC field), is first checked
      against the well-known theory of the AC permittivity of colloidal suspensions
      developed by DeLacey and White (E. H. B. DeLacey and L. R. White, J. Chem. Soc.
      Faraday Trans. 277, 2007 (1981)). We show that the derivative
      epsilon''(D)(omega)=-(pi/2)(partial differential epsilon'/partial differential ln
      omega) gives an excellent representation of the true imaginary part of the
      permittivity, epsilon''(omega). The technique is then applied to experimental
      data of the dielectric constant of polystyrene and ethylcellulose suspensions. We
      found that epsilon''(D) displays two separated behaviors when plotted against log
      omega in the frequency range 100 Hz-1 MHz: a monotonous decrease (associated with
      EP) followed by an absorption peak (associated with the double-layer relaxation,
      or alpha-relaxation). Interestingly, they are separated enough to make it
      possible to easily find the characteristic frequency of the alpha-relaxation.
      Fitting a relaxation function to epsilon''(D)(omega) after eliminating the part
      due to EP, we could calculate the real part epsilon'(omega) and compare it to the
      DeLacey and White (DW) theoretical predictions. A significantly better agreement
      between DW calculations and experimental epsilon'(omega) data is obtained when
      the logarithmic derivative method is used, as compared to the classical electrode
      separation techniques.

PMID- 16290606
TI  - Thiosalicylic acid-functionalized silver nanoparticles synthesized in one-phase
      system.
AB  - A series of silver colloidal dispersions were prepared by two protocols, i.e.,
      addition of the reductant-NaBH(4) and the stabilizer-thiosalicylic acid (TSA)
      into Ag(+) solution simultaneously or successively. The products were compared
      and characterized by TEM, electrochemical measurements, XPS, UV-vis, and FT-IR
      spectra. The size distributions of the Ag nanoparticles prepared by the former
      and latter protocols are bimodal and monodisperse, respectively. The analytic
      results of UV-vis spectra coincide with the TEM observation. A tentative
      explanation was given to the relationship between particle sizes and different
      synthetic protocols. The changes of the reduction potential of the reductant
      invoked a variance in particle diameter and size distribution. Electrochemical
      measurements corroborated our assumption. The composition information of TSA
      derived silver nanoparticles was obtained from XPS and FT-IR spectroscopic
      measurements.

PMID- 16290608
TI  - Mass transfer from an oscillating microsphere.
AB  - The enhancement of mass transfer from single oscillating aerocolloidal droplets
      having initial diameters approximately 40 microm has been measured using
      electrodynamic levitation to trap and oscillate a droplet evaporating in nitrogen
      gas. The frequency and amplitude of the oscillation were controlled by means of
      ac and dc fields applied to the ring electrodes of the electrodynamic balance
      (EDB). Elastic light scattering was used to size the droplet. It is shown that
      the mass transfer process for a colloidal or aerocolloidal particle oscillating
      in the Stokes flow regime is governed by a Peclet number for oscillation and a
      dimensionless oscillation parameter that represents the ratio of the diffusion
      time scale to the oscillation time scale. Evaporation rates are reported for
      stably oscillating droplets that are as much as five times the rate for
      evaporation in a stagnant gas. The enhancement is substantially larger than that
      predicted by quasi-steady-flow mass transfer.

PMID- 16290607
TI  - The synthesis and magnetic properties of nanosized hematite (alpha-Fe2O3)
      particles.
AB  - The synthesis of nanosized superparamagnetic hematite particles by dissolving
      ferric salts in hydrochloric acid and heating at 100 degrees C is described. A
      hydrolysis reaction causes the formation of hematite particles. The influence of
      the sequence of additions on the resulting precipitates was studied using TEM and
      XRD. The magnetic behavior was characterized by magnetization measurements. It
      was found that small changes in the reaction conditions led to remarkable changes
      in final size and shape of the hematite crystallites. A well-defined subrounded
      morphology and an average diameter of 41 nm were obtained for superparamagnetic
      hematite particles. This is the largest size reported thus far for superpara
      magnetic hematite particles.

PMID- 16290609
TI  - Formation and characterization of high surface area thermally stabilized
      titania/silica composite materials via hydrolysis of titanium(IV) tetra
      isopropoxide in sols of spherical silica particles.
AB  - A direct synthetic route leading to titania particles dispersed on nonporous
      spherical silica particles has been investigated; 5, 10, and 20% (w/w)
      titania/silica sols mixtures were achieved via hydrolyzation of titanium tetra
      isopropxide solution in the mother liquor of a freshly prepared sol of spherical
      silica particles (Stober particles). Titania/silica materials were produced by
      subsequent drying and calcination of the xerogels so obtained for 3 h at 400 and
      600 degrees C. The materials were investigated by means of thermal analyses (TGA
      and DSC), FT-IR, N(2) gas adsorption-desorption, powder X-ray diffraction (XRD),
      and transmission electron microscopy (TEM). In spite of the low surface area
      (13.1 m(2)/g) of the pure spherical silica particles calcined at 400 degrees C,
      high surface area and mesoporous texture titania/silica materials were obtained
      (e.g., S(BET) ca. 293 m(2)/g for the 10% titania/silica calcined at 400 degrees
      C). Moreover, the materials were shown to be amorphous toward XRD up to 600
      degrees C, while reasonable surface areas were preserved. It has been concluded
      that dispersion of titania particles onto the surface of the nonporous spherical
      silica particles increase their roughness, therefore leading to composite
      materials of less firm packing and mesoporosity.

PMID- 16290610
TI  - Redox behavior of Re(V)-amino acid containing complexes.
AB  - Three cationic complexes containing the [Re((V))O](3+) core (general formula
      [ReO(dien-H)(aa)](+), dien=diethylenetriamine, aa=glycine, alanine, valine) were
      studied on polycrystalline Au electrodes employing cyclic voltammetry techniques.
      The electrochemical behavior of the amino acids (aa) was also evaluated.
      Experiments were performed at pH 7.0 aqueous solutions at room temperature. The
      voltammogram of the complex showed current contributions related to the
      [Re((VI))O](4+)/[Re((V))O](3+) redox couple, the counterion, and the amino acid
      ligand.

PMID- 16290611
TI  - Interparticle interactions affecting the stability of sludge flocs.
AB  - Interparticle interactions affecting the stability of sludge flocs taken from
      laboratory-scale sequencing batch reactors at different solids retention times
      (SRTs) were investigated in batch experiments by varying the pH, ionic strength,
      cation valence, and urea and ethylenediaminetetraacetate concentrations of
      suspending solutions. The ultrastructure of sludge floc surfaces was observed by
      transmission electron microscopy. Changes in dissociation constants of sludge
      flocs under different conditions indicated that ionic interactions and hydrogen
      bonds held flocs together and compensated for the negative influence of
      electrostatic interactions on the stability of sludge flocs. Ionic interactions
      and hydrogen bonds were two dominant forces that maintained the stability of
      sludge flocs at lower SRTs; other mechanisms, such as physical enmeshment and van
      der Waals and/or hydrophobic interactions, were more important in controling the
      stability of sludge flocs at higher SRTs. Sludge flocs at higher SRTs (16 and 20
      days) were physically more stable than those at lower SRTs (4 and 9 days). A
      conceptual model of floc structure, based on interparticle interactions, for
      describing the stability of sludge flocs is proposed. The floc matrix is proposed
      to consist of two physically distinct regions that are defined by the arrangement
      of extracellular polymeric substances (EPS). These are likely to be
      differentially affected by the agents applied to manipulate interparticle forces.
      Thus, the heterogeneity in the packing of and the type of EPS reflects the
      stability of the floc.

PMID- 16290612
TI  - Mixing of partially fluorinated carboxylic acids with their hydrocarbon analogs
      at the air-water interface.
AB  - The mixing behavior of 1-(perfluorobutyl)undecanoic acid-pentadecanoic acid
      (C15), 1-(perfluorohexyl)undecanoic acid-heptadecanoic acid (C17), and 1
      (perfluorooctyl) undecanoic acid-nonadecanoic acid (C19) mixtures was
      investigated at the air-water interface. The compression isotherms of the
      fluorocarbon acid-hydrocarbon acid mixtures were recorded at various compositions
      on hydrochloric acid (pH 1.9, 37+/-2 degrees C) as a subphase. The phase
      transition, limiting molecular area, area at collapse pressure, and collapse
      pressure were determined for all pi-A isotherms. The mixing behavior was assessed
      by analyzing the concentration dependence of the average molecular area at
      constant film pressure (area/mole fraction or A-X diagram) and the concentration
      dependence of the phase transition, where possible. All three acid mixtures show
      a negative deviation from ideal behavior at surface pressures between 5 and 20
      mN/m, which is indicative of an attractive interaction of both compounds in the
      mixed monolayer at the air-water interface. The miscibility apparently decreases
      with increasing chain length of the carboxylic acids (C15>C17>C19).

PMID- 16290613
TI  - Structural and topographical characteristics of dipalmitoyl phosphatidic acid in
      Langmuir monolayers.
AB  - Dipalmitoyl phosphatidic acid (DPPA) monolayers at the air-water interface were
      studied from surface pressure (Pi)-area (A) isotherms and at the microscopic
      level with Brewster angle microscopy (BAM) under different conditions of
      temperature, pH, and ionic strength. BAM images were recorded simultaneously with
      Pi-A isotherms during the monolayer compression-expansion cycles. DPPA monolayers
      show a structural polymorphism from the liquid-expanded (LE)-liquid-condensed
      (LC) transition region at lower surface pressures toward liquid-condensed and
      solid (S) structures at higher surface pressures. An increase in temperature, pH,
      or ionic strength provokes an expansion in the monolayer structure. The results
      obtained from the Pi-A measurements are confirmed by the monolayer topography and
      relative reflectivity. The measurements of relative reflectivity upon monolayer
      compression showed an increase in relative monolayer thickness of 1.25 and 3.3
      times throughout the full monolayer compression from the liquid-expanded to the
      liquid-condensed and solid states, respectively.

PMID- 16290614
TI  - Black foam films from aqueous solutions of a mixture of phospholipids and a
      permeation enhancer.
AB  - The influence of a permeation enhancer on the properties of phospholipid black
      foam films has been studied through the combination of three complementary
      techniques: surface tension measurements, X-ray reflectivity, and the
      "diminishing bubble" method. This permeation enhancer is said to optimize the
      delivery of active ingredients into or through the stratum corneum: the 4-decyl
      oxazolidin-2-one. We made films of a complex phospholipid mixture that mimic the
      behavior of the enhancer in a membrane cell. Mixed phospholipids/4-decyl
      oxazolidin-2-one/NaCl solutions were studied with various 4-decyl oxazolidin-2
      one concentrations. Stable black films were obtained and their thicknesses
      examined. The evolution of the coefficient of gas permeability with 4-decyl
      oxazolidin-2-one concentration is also addressed.

PMID- 16290615
TI  - The effect of the salt concentration and counterion valence on the aggregation of
      latex particles at the air/water interface.
AB  - An experimental study on colloidal aggregation in two dimensions is presented.
      This study shows that a high amount of electrolyte concentration is necessary to
      screen the particle interactions and to induce the aggregation process. Our
      results indicate that the stability of the colloidal particles, with a diameter
      of 735 nm, increases when they are trapped at the air-water interface. The reason
      for this stability is the existence of long-range repulsive interactions between
      the external parts of the particles that are propagated at the air phase. The
      subphase electrolyte concentration that separates the slow aggregation rate
      region from the fast aggregation rate region, the critical coagulation
      concentration (C.C.C.), has been determined for counterions with a different
      valence. Two regimes can be distinguished: at low salt concentration the
      aggregation process becomes slower and the aggregation is reaction limited. At
      high ionic strength the repulsive interactions between the immersed part of the
      particles are very weak and the aggregation rate tends to grow. However, because
      of the aerial repulsive interactions, pure diffusion-limited cluster aggregation
      is never found.

PMID- 16290616
TI  - Rheological characterization, crystallization, and gelation behavior of
      monoglyceride gels.
AB  - Saturated monoglycerides can form firm gels in water. These gels are networks of
      stiff plate-like beta-crystals of monoglycerides (a "cardhouse"), grown from a
      space-filling lamellar liquid-crystalline phase. The molecular mechanism of
      crystallization is discussed in the light of network formation. The concentration
      dependence of gel development of (shear-cooled) monoglyceride gels has been
      studied by rheology. A gelation mechanism has been proposed, consisting of two
      steps: (i) After formation of a nucleus, rapid crystallization in a lateral
      direction occurs (probably within one bilayer) by which the first space-filling
      network is formed. (ii) This is followed by reinforcement of the network by which
      stacks of crystalline bilayers are formed. The plate-like crystals are linked in
      connective domains or junction zones, probably containing all the material
      (cosurfactants, diglycerides, etc.) that does not fit in the crystalline array.
      Small deformation rheology shows that above about 2 wt% monoglyceride a
      percolating network is formed. The large deformation rheology is typical for a
      particle gel with a relatively small strain at failure (both in shear deformation
      and compression). The connective domains or junction zones already fail when
      relatively small deformations are put on the system.

PMID- 16290617
TI  - Influence of ozonized kraft lignin on the crystallization of CaCO3.
AB  - Results are reviewed from a study examining how structural modifications
      introduced by ozonization enhance the influence of kraft lignin on the
      crystallization of CaCO(3). Ozone treatment of kraft lignin in an aqueous
      environment is shown to increase its carboxylic acid and overall oxygen content
      and reduce its molecular weight. Calcium concentration and temperature were
      monitored in heated supersaturated solutions containing ozonized kraft lignins to
      gauge their influence on CaCO(3) crystallization processes. The presence of kraft
      lignin raises the temperature necessary to induce crystallization. This effect is
      shown to level off at relatively low lignin concentrations and be dependent on
      the extent of ozone treatment the kraft lignin has undergone. A linear
      correlation is found between crystallization temperatures and the carboxylic acid
      content of ozonized lignin samples indicating the introduction of these
      functional groups plays an important role in enhancing its inhibitory effect.
      Scanning electron microscopy images of crystals grown in the presence of kraft
      lignins show significant morphological modifications. These are consistent with
      specific or pseudo specific interactions between the lignin and crystal faces of
      calcite to inhibit growth parallel to its c axis. The influence over crystal
      morphology demonstrated by modified kraft lignin increases with increasing
      ozonization. Also presented here are crystallization temperature data for a range
      of kraft lignin ultrafiltration fractions, which indicate that the optimal
      (nominal) molecular weight of kraft lignin for inhibiting the crystallization of
      CaCO(3) lies between 5000 and 10000.

PMID- 16290618
TI  - Spreading and infiltration of inkjet-printed polymer solution droplets on a
      porous substrate.
AB  - Simultaneous spreading and infiltration of inkjet-printed droplets has been
      studied. Small (54- and 63-microm diameter) droplets of an aqueous polymer
      solution (2.4 vol% polyacrylic acid, PAA, MW 60,000) were deposited on high green
      density porous ceramic beds, and the wetting-induced spreading and infiltration
      of the droplets were characterized. The time scales for spreading and
      infiltration were comparable (approximately milliseconds), resulting in
      interruption of the spreading prior to completion by infiltration of the liquid
      into the powder bed, a situation that has received little treatment in the
      literature. The infiltration time was varied by changing the pore size (via
      particle size) in the powder bed, and it was confirmed that slower infiltration
      resulted in greater spreading of the liquid. The spreading and infiltration of
      the droplet were modeled to examine the coupling between the two processes and
      allow prediction of the maximum extension of the droplet as a function of the
      powder bed particle size. The liquid spreading was found to follow r(t)=a(b+t)(n)
      behavior, and the effect of particle size on infiltration time was used to
      predict the point at which spreading ceases due to infiltration for various
      particle sizes.

PMID- 16290619
TI  - Surface characterization of synthetic and mineral carbonate fluoroapatites.
AB  - As part of a larger project concerning the sorption capacities of carbonate
      fluoroapatites, the physical and surface properties of the synthetic carbonate
      fluoroapatite and mineral francolite retained for this work have been carefully
      examined. The average particle size of the powdered samples, determined by laser
      granulometry, is around 30 microm. Their specific surface areas, measured
      according to the N(2) BET method, are 8.8+/-0.1 and 13.9+/-0.1 m(2).g(-1),
      respectively, for the synthetic and the mineral compound. The solubility of both
      solids has been studied under undersaturation initial conditions. The synthetic
      compound has a solubility product of 10(-103+/-2), but the mineral francolite,
      which is highly substituted and poorly crystalline, is more soluble and dissolves
      incongruently. The amphoteric properties of the hydrous carbonate fluoroapatites
      surfaces have also been investigated through zeta-potential measurements and
      potentiometric titrations in KNO(3) medium at 25 degrees C. The experimental data
      have been interpreted using the computer program FITEQL 3.2, applying either the
      nonelectrostatic or the constant capacitance model. For both solids, the values
      of the surface acidity constants determined with the two models are very close,
      suggesting a weak contribution of the electrostatic interactions. Moreover, the
      more acidic surface of the synthetic compound compared to that of the mineral one
      is assigned to the differences in crystallinity and chemical composition between
      the two solids.

PMID- 16290620
TI  - Pore structure and fractal characteristics of activated carbon fibers
      characterized by using HRTEM.
AB  - The pore microstructures in two viscouse rayon-based ACF samples were
      characterized by nitrogen adsorption and HRTEM. For TEM, a two-dimensional fast
      Fourier transform (FFT) of the original TEM images was performed, and pores in
      different size ranges were extracted by the inverse FFT (IFFT) operation. The
      surface fractal dimensions of the samples were evaluated by using both N(2)
      adsorption and TEM image analysis. The results show that TEM can portray the
      shapes of the pore, and it can give a quantitative evaluation of surface
      irregularity that is consistent with nitrogen adsorption results.

PMID- 16290621
TI  - Pore structure and surface properties of chemically modified activated carbons
      for adsorption mechanism and rate of Cr(VI).
AB  - Effects of hydrochloric acid and sodium hydroxide treatments of activated carbons
      (ACs) on chromium(VI) reduction were studied. The surface properties were
      determined by pH, acid-base values, FT-IR, and X-ray photoelectron spectrometer
      (XPS). And the porous structure of the activated carbons was characterized by
      adsorption of N(2)/77 K. The Cr(VI) adsorption experiments were carried out to
      analyze the influence of porous texture and surface properties changed by the
      chemical surface treatments of ACs on adsorption rate with carbon-solution
      contact time. From the experimental results, it was observed that the extent of
      adsorption and reduction processes depends on both microporous structure and
      functional groups. And the adsorption of Cr(VI) ion was more effective in the
      case of acidic treatment on activated carbons, resulting from the increases of
      acid value (or acidic functional group) of activated carbon surfaces. However,
      basic treatment on activated carbons was not significantly effective on the
      adsorption of Cr(VI) ion, probably due to the effects of the decrease of specific
      surface area and basic Cr(VI) in nature.

PMID- 16290622
TI  - In situ synthesis of polysulfides covalently bonded to silica.
AB  - Silanol groups, triple bond SiOH, on the surface of silica were esterified with
      unsaturated alcohols and long-chain alcohols bearing thiol groups. The modified
      silicas obtained were used as substrates for a vulcanization-analogous reaction
      with sulfur catalyzed by zinc dimethyldithiocarbamate. Surface-esterified thiols
      could be smoothly converted to bridged polysulfides bonded to the silica surface,
      whereas the use of surface-esterified unsaturated alcohols led to removal of the
      surface-esterified alcohol from the silica surface. The materials were
      characterized by solid-state NMR and thermal and microanalytical analysis. The
      linking of surface-esterified alkenols and thiols by sulfide bridges was
      investigated by a numerical model for a flat surface. This showed that for a
      typical density of 3-4 micromol/m(2) surface groups, a statistical maximum of 70
      75% of groups could be linked by S(n) bridges (n=2-4).

PMID- 16290623
TI  - Effects of antimony on the surface tension of molten silicon.
AB  - The effect of antimony concentration (C(Sb)/mass%) on the surface tension of
      molten silicon has been determined with the sessile drop method in the
      temperature range from 1693 to 1773 K and in the range of the oxygen partial
      pressure, Po(2), in an Ar atmosphere from 10(-23) to 10(-21) MPa. The results
      show that the surface tension of molten silicon decreases with increasing Sb
      concentration in the range of C(Sb)<0.9 mass%, which indicates positive
      adsorption of Sb in molten silicon and can be fairly described with the
      Szyszkowski's equation. The maximum decrease rate of surface tension is about 65
      mN m(-1) (mass% C(Sb))(-1), and the temperature coefficient of surface tension,
      (partial differential sigma/ partial differential T)C(Sb), increases with
      increasing C(Sb). The evaporation of the systems was only observed between the
      melting points of antimony (904 K) and silicon (1683 K), and the surface tension
      presents no dependence on measuring time above the melting point of silicon.

PMID- 16290624
TI  - Bubble shapes and orientations in low Re simple shear flow.
AB  - We present measurements of shape and orientation of air bubbles in a viscous
      Newtonian fluid deformed by simple shear. The apparatus is a variation of the
      "parallel band" device developed by G. I. Taylor. Previous experimental studies
      on low viscosity ratio, low Reynolds number (Re << 1) bubble deformation have
      focussed on either small or large deformations (mostly small deformation) and
      have only qualitatively examined the orientation of bubbles except for small
      deformations. Our data set spans both the theoretical small deformation and high
      deformation limits. With these data we confirm theoretical relationships and
      assess the range of capillary numbers (Ca) over which theoretical relationships
      for shape and orientation of bubbles are appropriate. We also examine the
      geometry of deformed bubbles as they relax to a spherical shape once shear
      stresses are removed. Our data indicate that for extremely small Reynolds numbers
      and viscosity ratios, the small deformation theoretical relationship first
      developed by Taylor, is a good approximation for Ca<0.5. The large deformation
      results for both shape and bubble orientation derived by Hinch and Acrivos agree
      with our data for Ca>1 and Ca>0.5, respectively.

PMID- 16290625
TI  - Mixed micellar aggregates of nonionic and anionic surfactants with short
      hydrophobic tails: a microcalorimetric study.
AB  - Apparent molar relative enthalpies were measured for the nonionic ethoxylated
      surfactant CH(3)-(CH(2))(5)-(OCH(2)-CH(2))(5)OH (C(6)E(5)) in aqueous solution at
      constant molality of the ionic surfactant CH(3)-(CH(2))(5)-SO(-)(3)Na(+)(C(6)SNa)
      at 25 degrees C. The experimental data obtained by a stepwise dilution process
      allowed evaluation of the C(6)E(5) first interaction parameter at several
      constant molalities of C(6)SNa. The C(6)E(5) critical micelle composition as a
      function of the C(6)SNa molality was also estimated. The experimental
      calorimetric data, together with the mixed micelles composition computed in the
      past by some of us [Ciccarelli et al., Langmuir 14, 7130 (1998)], allowed
      computation of the Deltah(Mic) of micellization. The experimental data are
      compared to those predicted by the ideal solution model and regular solution
      model of mixed micellization. From a calorimetric study performed on the water
      hexanol-C(6)SNa and water-penthaethylene glycol-C(6)SNa model systems, it can be
      argued that the interactions among the hydrophilic heads in the C(6)E(5)-C(6)SNa
      mixed micelles prevail on the contribution of the hydrophobic tails in ruling the
      enthalpic properties of the system.

PMID- 16290626
TI  - Micro volume changes due to Pb(II) and Cu(II) sorption on amorphous Fe(III)
      hydroxide.
AB  - Micro volume changes due to Pb(II) and Cu(II) sorption on amorphous Fe(III)
      hydroxide (AFH) were determined by a dilatometer at pH 4.50. Volume change is
      attributed to change in hydration status of dissolved and/or suspended
      substances. The volume of the system increased due to Pb(II) and Cu(II) sorption,
      suggesting that water molecules hydrated around Pb(II) or Cu(II) ions and AFH
      were released during sorption. Volume increases due to Pb(II) and Cu(II) sorption
      were smaller than those due to bulk precipitation of Pb and Cu hydroxides.
      Precipitation of Pb(II) and Cu(II) was not likely to occur at pH 4.50 in the
      presence of AFH. In conclusion, Pb(II) and Cu(II) formed an inner-sphere complex
      on AFH at pH 4.50, keeping hydrated water on the adsorbed species. Adsorbed
      Cu(II) kept more hydrated water than adsorbed Pb(II) on AFH.

PMID- 16290628
TI  - Particle size effects on uptake of heavy metals from sewage sludge compost using
      natural zeolite clinoptilolite.
AB  - Land application of sewage sludge may be the least energy consuming and the most
      cost-effective means of sludge disposal or utilization. However, the major
      technical problem with land application of sludge concerns the high
      concentrations of heavy metals. These metals may be leached and enter the
      ecosystem, the food chain, and eventually the human population. This paper deals
      with the removal of heavy metals from sewage sludge compost using natural zeolite
      clinoptilolite, in respect to the particle size. The final results indicate that
      heavy metals can be sufficiently removed by using 25% w/w of zeolite with
      particle size of 3.3-4.0 mm. Pore clogging and structural damage in smaller
      particle sizes is probably the reason for lower uptake of metals by the latter.

PMID- 16290629
TI  - Porous structure of activated carbons and tert-butylbenzene breakthrough
      dynamics.
AB  - The structural and adsorptive characteristics of six activated carbons were
      studied by means of nitrogen and benzene adsorption and water desorption. Tert
      butylbenzene (TBB) breakthrough dynamics was analyzed by using several integral
      equations solved with a regularization/singular-value decomposition procedure.
      TBB interaction with texturally different activated carbons with the presence of
      preadsorbed or adsorbed water under dynamic conditions was illustrated by the
      breakthrough plots handled with several models. The influence of the type of
      activated carbons, their pore size distributions, water vapor, and TBB flow rate
      on the breakthrough times (tb) and the dynamic capacity of the carbon beds has
      been explored with better results for a carbon sample possessing a maximal
      contribution of mesopores at half-width x>1.5 nm among the carbons studied (which
      also appears on benzene adsorption) and a major contribution of microporocity as
      VDS/Vp approximately 0.88 and SK/SBET approximately 0.15. Another adsorbent,
      which is characterized by a similar total porosity but a larger micropore volume,
      a smaller contribution of mesopores (SK/SBET approximately 0.08), greater total
      and miroporous specific surface areas, and greater intensity of the pore size
      distribution at x<1.5 nm, shows the second result in dynamic TBB retention.

PMID- 16290630
TI  - Electrosorption of ions from aqueous solutions by nanostructured carbon aerogel.
AB  - Electrosorption is generally defined as potential-induced adsorption on the
      surface of charged electrodes. After polarization of the electrodes, ions are
      removed from the electrolyte solution by the imposed electric field and adsorbed
      onto the surface of the electrodes. Experimental and modeling studies were
      conducted using two types of carbon aerogel composites of different surface areas
      to provide a better understanding on the mechanisms of electrosorption. The
      experimental results revealed that no significant specific adsorption of F- ions
      occurred, while strong specific adsorption was observed for NO3- and Cu2+ ions.
      In addition, although the two types of carbon aerogel electrodes had different
      surface areas, their capacities were found to be very similar because of the
      electrical double-layer overlapping effect in micropores. An electrical double
      layer model developed in our previous work (16), in which the electrical double
      layer overlapping correction is included, is expanded in the present work by
      considering the effect of the specific adsorption on the electrosorption process.
      Modeling results were compared with experimental data obtained under various
      conditions. When the overlapping effect and specific adsorption were considered,
      the model provided results that were in good agreement with experimental data.

PMID- 16290632
TI  - Growth of filamentous carbon from the surface of Ni/SiO2 doped with alkali metal
      bromides.
AB  - The growth of ordered filamentous carbon, catalytically generated from the
      decomposition of ethylene, has been studied over the temperature range 673-898 K
      using an 11% w/w Ni/SiO2 catalyst doped to varying degrees (0.1-9.3% w/w) with a
      range of alkali metal bromides. The effect of these alkali metal/halogen adatoms
      in promoting/inhibiting carbon growth has been assessed and variations in the
      associated carbon structural characteristics have been examined. The introduction
      of Li consistently promoted filamentous carbon growth (where 723 K<T<823 K) while
      the presence of Na, K, Rb, or Cs resulted in an equivalent or lower carbon yield.
      The degree of carbon deposition was strongly dependent on the nature and loading
      of the alkali metal, the Ni/Br ratio in the activated catalyst, and reaction
      temperature; conditions for optimum carbon growth are identified. The response of
      carbon yield and structural order to alkali bromide doping is discussed in terms
      of Ni particle electronic structure and metal/support interaction(s). High
      resolution transmission electron microscopy (HRTEM) has been used to probe the
      filamentous carbon structure and the dispersion/morphology/size of the supported
      Ni crystallites. Highly curved and helical filaments predominated over the doped
      (particularly CsBr) samples and this is attributed to a disruption in carbon
      diffusion through the Ni particle caused by a spreading/coating of the particle
      by the alkali adatom. Temperature-programmed oxidation studies have highlighted
      the changes in the graphitic nature of the carbon due to catalyst doping; the
      results are consistent with the TEM analysis.

PMID- 16290631
TI  - Kinetics of adsorption of high molecular weight anionic polyacrylamide onto
      kaolinite: the flocculation process.
AB  - The adsorption kinetics of anionic polyacrylamide flocculant onto kaolinite clay
      are examined as a function of flocculant dosage and pH. Special attention has
      been given to the flocculation effect during the adsorption process and the
      resulting inhibition of further adsorption. At pH 8.5 the adsorption capacity of
      anionic polyacrylamide on kaolinite is low while at pH 4.5, the adsorption
      capacity increases. Flocculant adsorption has been shown to be related to the
      amount of available surface area, pH, flocculant dosage, and the resulting floc
      strength, which controls the rate of new surface area exposure and hence the
      continuation of further adsorption. At both pH 4.5 and pH 8.5, complete
      adsorption is achieved at low flocculant dosages and adsorption equilibrium is
      achieved at high flocculant dosages after 1 day. In contrast, at intermediate
      flocculant dosages adsorption equilibrium is not reached over a 7-day period, due
      to a continuously increasing surface area.

PMID- 16290633
TI  - Modeling of gas adsorption equilibrium over a wide range of pressure: a
      thermodynamic approach based on equation of state.
AB  - A thermodynamic approach based on the Bender equation of state is suggested for
      the analysis of supercritical gas adsorption on activated carbons at high
      pressure. The approach accounts for the equality of the chemical potential in the
      adsorbed phase and that in the corresponding bulk phase and the distribution of
      elements of the adsorption volume (EAV) over the potential energy for gas-solid
      interaction. This scheme is extended to subcritical fluid adsorption and takes
      into account the phase transition in EAV. The method is adapted to gravimetric
      measurements of mass excess adsorption and has been applied to the adsorption of
      argon, nitrogen, methane, ethane, carbon dioxide, and helium on activated carbon
      Norit R1 in the temperature range from 25 to 70 degrees C. The distribution
      function of adsorption volume elements over potentials exhibits overlapping peaks
      and is consistently reproduced for different gases. It was found that the
      distribution function changes weakly with temperature, which was confirmed by its
      comparison with the distribution function obtained by the same method using
      nitrogen adsorption isotherm at 77 K. It was shown that parameters such as pore
      volume and skeleton density can be determined directly from adsorption
      measurements, while the conventional approach of helium expansion at room
      temperature can lead to erroneous results due to the adsorption of helium in
      small pores of activated carbon. The approach is a convenient tool for analysis
      and correlation of excess adsorption isotherms over a wide range of pressure and
      temperature. This approach can be readily extended to the analysis of
      multicomponent adsorption systems.

PMID- 16290634
TI  - A linear comprehensive adsorption model of hydrogen on super activated carbon
      under supercritical conditions.
AB  - The adsorption isotherms of hydrogen on super activated carbon were measured
      systematically, covering a temperature range of 93-293 K at 20 K intervals and
      pressures up to 7 MPa. All the experimental data were linearized by adopting the
      coordinates ln ln(n) vs 1/(ln P). The results indicate that the adsorption limit
      (P(lim), n(lim)) exists virtually at high pressure and has a certain physical
      meaning. Based on the adsorption limit, further analyses were carried out by
      modeling the adsorption isotherms in the coordinates ln(n(lim)/n) vs
      ln(RT(ln(P(lim)/P) and a linear comprehensive adsorption model was proposed in
      the form n (lim)=n.exp(psi T+lambda/T-c/) (beta).[RT ln( P (lim)P )] (b) which
      can predict the adsorption isotherm of hydrogen on activated carbon in
      supercritical conditions.

PMID- 16290635
TI  - Application of a single model to study the adsorption equilibrium of prednisolone
      on six carbonaceous materials.
AB  - The knowledge of sorption processes of nonelectrolytes in solution by solid
      adsorbents implies the study of kinetics, equilibrium, and thermodynamic
      functions. However, quite frequently the equilibrium isotherms are studied by
      comparing them with those corresponding to the Giles et al. classification (1);
      these isotherms are also analyzed by fitting them to equations based on
      thermodynamic or kinetic criteria, and even to empirical equations. Nevertheless,
      information obtained is more coherent and satisfactory if the adsorption
      isotherms are fitted by using an equation describing the equilibrium isotherms
      according to the kinetic laws. These mentioned laws would determine each one of
      the unitary processes (one or more) which condition the global process. In this
      paper, an adsorption process of prednisolone in solution by six carbonaceous
      materials is explained according to a previously proposed single model, which
      allows to establish a kinetic law which fits satisfactorily most of C vs t
      isotherms (2). According to the above-mentioned kinetic law, equations describing
      sorption equilibrium processes have been deducted, and experimental data points
      have been fitted to these equations; such a fitting yields to different values of
      adsorption capacity and kinetic equilibrium constants for the different processes
      at several temperatures. However, in spite of their practical interest, these
      constants have no thermodynamic signification. Thus, the thermodynamic
      equilibrium constant (K) has been calculated by using a modified expression of
      the Gaines et al. equation (3). Global average values of the thermodynamic
      functions have also been calculated from the K values. Information related to
      variations of DeltaH and DeltaS with the surface coverage fraction was obtained
      by using the corresponding Clausius-Clapeyron equations.

PMID- 16290636
TI  - Structures of beta-FeOOH particles formed in the presence of Ti(IV), Cr(III), and
      Cu(II) ions.
AB  - beta-FeOOH particles were prepared by aging aqueous FeCl3 solutions containing
      Ti(IV), Cr(III), and Cu(II) at room temperature for 360 days. The structures of
      the formed particles were investigated by various techniques including TEM, XRD,
      XAFS, and adsorption of N2 and H2O. Ti(IV) markedly impeded the crystallization
      and particle growth of beta-FeOOH by coprecipitation with Fe(III) and disturbing
      the short-range structure of beta-FeOOH particles. In the presence of a large
      amount of Ti(IV), it was pronounced that the hydrolysis of Ti(IV) impeded beta
      FeOOH formation by reducing the solution pH, whereas Cr(III) and Cu(II), which
      were hardly involved in the products, gave rise to no noticeable effects on the
      formation of beta-FeOOH particles. The knowledge obtained in this study can be
      available for interpretation of the anti-corroding function of Ti alloyed with
      steels in a Cl- -containing environment.

PMID- 16290637
TI  - Synthesis and characterization of silica/poly (methyl methacrylate) nanocomposite
      latex particles through emulsion polymerization using a cationic azo initiator.
AB  - Following a previous work (J. L. Luna-Xavier et al., Colloid Polym. Sci.279, 947
      (2001)), silica-poly (methyl methacrylate) (PMMA) nanocomposite latex particles
      have been synthesized in emulsion polymerization using a cationic initiator, 2,2'
      azobis (isobutyramidine) dihydrochloride (AIBA), and a nonionic polyoxyethylenic
      surfactant (NP30). Silica beads with diameters of 68, 230, and 340 nm,
      respectively, were used as the seed. Coating of the silica particles with PMMA
      was taking place in situ during polymerization, resulting in the formation of
      colloidal nanocomposites with a raspberry-like or a core-shell morphology,
      depending on the size and nature of the silica beads. The amount of surface
      polymer was quantified by means of ultracentrifugation and thermogravimetric
      analysis as extensively described in the first article of the series (see above
      reference). The influence of some determinant parameters such as the pH of the
      suspension, the initiator, silica, monomer, or surfactant concentration on the
      amount of coating polymer and on the efficiency of the coating reaction was
      investigated in details and discussed in light of the physicochemical properties
      of the seed mineral. Electrostatic attraction between the positive end groups of
      the macromolecules and the inorganic surface proved to be the driving force of
      the polymer assembly on the seed surface at high pH, while polymerization in
      adsorbed surfactant bilayers (so-called admicellar polymerization) appeared to be
      the predominant mechanism of coating at lower pH. Optimal conditions have been
      found to reach high encapsulation efficiencies and to obtain a regular polymer
      layer around silica.

PMID- 16290638
TI  - Effect of KOH activation on the formation of oxygen structure in activated
      carbons synthesized from polymeric precursor.
AB  - In this work, the influence of KOH activation on the surface chemistry of
      activated carbons (ACs) synthesized from polystyrene-based cation exchangeable
      resin (PSI) has been investigated. The surface chemistry of ACs has been
      characterized by using Fourier transformed infrared spectroscopy (FT-IR), X-ray
      photoelectron spectroscopy (XPS), pH measurement, and Boehm's titration method.
      As a result, PSI can be successfully converted into ACs with high porosities. The
      total oxygen content on the ACs studied increases with increasing the KOH-to-PSI
      ratio. FT-IR and XPS analyses show that the resulting carbons possess a number of
      oxygen surface functional groups, such as carbonyl, quinone, phenol, ether, and
      carboxylic acid groups. The highest oxygen content and acid value are observed at
      a KOH-to-PSI ratio of 4 (KPS-4). However, its pH and surface basicity are higher
      than those of a KOH-to-PSI ratio of 2 (KPS-2), indicating the formation of basic
      species, such as quinone and pyrone groups. Although the oxygen-containing groups
      with basic character exist in the resulting carbons, all the samples are still
      acidic in character.

PMID- 16290640
TI  - Study of surface forces dependence on pH by atomic force microscopy.
AB  - We used an atomic force microscope to investigate silicon nitride tip
      interactions with various materials (copper, nickel, silicon carbide) as a
      function of pH. The electrolyte used was 10(-3) M NaCl and the interactions
      observed through force versus distance curves (attraction or repulsion) depended
      on the pH value. Interaction forces calculation was derived from force versus
      distance curve data and the results are discussed in terms of electrostatic
      interactions using Zeta potential theory.

PMID- 16290639
TI  - Multiinstrument study of the electrophoretic mobility of quartz.
AB  - The electrophoretic mobility of quartz in 0.01 mol dm(-3) NaCl and NaNO3 over the
      pH range 2-8 was studied using five different commercial instruments. The
      mobilities over the pH range 4-8 were relatively consistent, but the mobilities
      over the pH range 2-4 and the position of the isoelectric point IEP varied from
      one instrument to another. This result suggests that the discrepancies in the
      apparent IEP of quartz (and other silicas) reported in the literature are due to
      the instrument artifacts.

PMID- 16290642
TI  - Enthalpic, entropic, and square gradient contributions to the surface energetics
      of amine-cured epoxy systems.
AB  - The evolution of surface tension during polymerization of three amine-cured epoxy
      systems was investigated. Due to the chemical reaction of the epoxy groups with
      primary and secondary amines, the energetic status of an epoxy-amine system
      increased during polymerization. At the same time, the polymerization process
      induced entropic variations, also contributing to the evolution of surface
      energetics. A simple relation expressing the surface tension as a function of the
      bulk energy, the entropy of the system, and the square gradient of the polymer
      density was derived. The bulk and surface energetics were expressed in terms of
      solubility parameter and surface tension, respectively. The former was predicted
      using the Van Krevelen group contribution method, while the latter was directly
      measured using the Wilhelmy wetting method. Results indicated that, in all the
      three epoxy-amine systems under investigation, a unique relationship combining
      the surface tension, the bulk energy, the entropy, and the density square
      gradient of the system could be used. On the basis of the present study, and
      taking into account all contributory factors, it was concluded that the enthalpy
      component to the surface energetics is the dominant contribution.

PMID- 16290641
TI  - On the stability of two rigidly rotating magnetic fluid columns in zero gravity
      in the presence of mass and heat transfer.
AB  - The stability of two rigidly rotating magnetic fluids separated by a cylindrical
      interface and stressed by a timely oscillating axial magnetic field is
      investigated. Only axisymmetric disturbances are considered. The interface admits
      both mass and heat transfer. Weak viscous effects on the interface are taken into
      account so that their contributions are demonstrated in the boundary conditions.
      The solution of the boundary value problem leads to a transcendental differential
      equation. It includes a periodic coefficient together with modified Bessel
      functions of operators involved as their arguments. In the absence of rotation
      and under the assumption of small amplitude of the harmonic magnetic field, the
      characteristic equation is analyzed by means of Whittaker's perturbation
      technique to determine the transition curves which separate stable from unstable
      solutions. While in the presence of rotation, the method of multiple-time scales
      is adopted to investigate the necessary and sufficient conditions for stability.
      The analysis results in the resonance cases as well as the nonresonance cases. In
      order to simplify the analysis, the periodic solutions are only considered.
      Therefore, stability is discussed through the marginal state. Furthermore, the
      rotation is considered as small. The analytical results are numerically
      confirmed.

PMID- 16290643
TI  - Surface pressure-area isotherms and fluorescent behavior of phospholipids
      containing labeled pyrene.
AB  - In this work, the surface and fluorescent behavior of three phospholipids
      containing a pyrene molecule in one of their hydrocarbon chains was studied.
      Differences between the isotherms provided by the different monolayers can be
      attributed to the orientation of the head group in the phospholipids at the
      air/water interface. This assertion is supported by the fluorescent behavior of
      monolayers of phospholipids containing labeled pyrene (Py-DPPE, Py-DPPC, and Py
      DPPG).

PMID- 16290645
TI  - Nanostructured gold hollow microspheres prepared on dissolvable ceramic hollow
      sphere templates.
AB  - Fifty and one-hundred micrometer diameter nanostructured gold hollow microspheres
      (GHSs), in >98% purity, have been prepared by using ceramic hollow spheres, CHSs,
      as templates. Tennanometer diameter gold nanoparticles were covalently linked to
      the thiol moiety of (3-mercaptopropyl)trimethoxysilane, which had been self
      assembled onto the CHSs. Greater structural strength was obtained by the
      generation of additional gold nanoparticles, in situ on the gold nanoparticle
      coated CHSs (by immersing the gold nanoparticle coated CHSs into an aqueous
      mixture of hydroxylamine and gold chloride). GHSs were obtained by dissolving the
      CHSs templates. The sizes, shapes, surface areas (185.3 m2/g for CHSs and 182.9
      m2/g for GHSs), pore diameters (7.7 nm for CHSs and 7.8 nm for GHSs), and pore
      volumes (0.41 cm3/g for CHSs and 0.36 cm3/g for GHSs) of GHSs were quite similar
      to their CHSs counterparts. Significantly, GHSs showed surface plasmon bands
      whose maximum (644 nm) shifted from that observed for the parent 10-nm gold
      nanoparticles (522 nm).

PMID- 16290644
TI  - Substrate monolayers as electrochemical sensing elements for alpha-chymotrypsin.
AB  - A disulfide, which carried two L-phenylalanyl p-nitroanilide (Phe-pNA) moieties
      at both ends, was prepared by the coupling of 11,11'-dithiodiundecanoic acid
      (DTUA) with Phe-pNA. The compound obtained (DTUA-Phe-pNA) formed a self-assembled
      monolayer (SAM) on a gold electrode and vacuum-evaporated gold thin film as
      proven by cyclic voltammetry, and reflection absorption spectroscopy,
      respectively. Incubation of alpha-chymotrypsin with the SAM-modified electrode
      induced both a decrease in anodic and cathodic peak currents (-DeltaIa and 
      DeltaIc) and an increase in potential difference (DeltaEp) in the cyclic
      voltammogram of potassium ferricyanide as a probe, which suggested the attack of
      the enzyme at the amide group between Phe and pNA groups of the SAM, resulting in
      the formation of an intermediate. The linear relationship between the initial
      rate of increase in the amount of enzyme bound to the SAM and in both DeltaIa
      (absolute value of the decrease in anodic peak current) and DeltaEp values was
      confirmed by the quartz crystal microbalance method. The binding rate of the
      enzyme to the Phe-pNA SAM was dependent on the surface density of the Phe-pNA
      group in the SAM. The alpha-chymotrypsin-induced increases in the DeltaIa and
      DeltaEp values were inhibited by the addition of N-acetyl-D-phenylalanine methyl
      ester (N-Ac-D-Phe-OMe). In contrast with alpha-chymotrypsin, trypsin did not show
      a significant increase in the DeltaIa and DeltaEp values upon incubation with Phe
      pNA-carrying SAM. These results could be attributed to the specific attack of
      alpha-chymotrypsin to the amide group in the SAM. The inhibition constant for N
      Ac-D-Phe-OMe in the SAM system was quite similar to that in the free substrate
      system, showing that the enzymatic reaction above the SAM proceeds in a similar
      way to that in the homogeneous solution system.

PMID- 16290646
TI  - Rennet-induced milk coagulation by continuous steady shear stress.
AB  - The effect of continuous steady shear stress (CSSS) on rennet-induced coagulation
      of milk was studied by measuring the change in viscosity of the system with time.
      Continuous shear stress (< or =0.5 Pa) applied during coagulation did not
      counteract the network formation at standard cheese-making conditions. In fact,
      CSSS of 0.2 Pa promoted coagulation by possibly increasing diffusion, collision,
      and hydrolization rates due to near-field, attractive hydrodynamic reactions.
      This was evidenced by the high viscosity of the resultant coagulum. However, the
      viscosity profile of the coagulum formed in the presence of CSSS followed the
      same trend as that formed in the absence of CSSS. Viscosity versus time profiles
      in both cases displayed an initial lag phase followed by a steady increase until
      a plateau value. The viscosity plateau reached under CSSS was marked with several
      sudden peaks, indicating the dynamic structure of the coagulum. These peaks in
      viscosity profiles began to appear after about 1380 s since rennet addition at
      standard cheese-making conditions. The time at which viscosity first exceeds 40
      kPa s was verified to coincide with manual determination of the time at which the
      coagulum is cut (i.e., cutting time) during cheese making.

PMID- 16290648
TI  - Optical aspects of Na+ ions adsorption on sol-gel porous films used in optical
      fiber sensors.
AB  - Adsorption of Na+ ions from water solutions on the surface of a porous silica
      layer covering the optical fiber core was studied. It was shown that Na+ ions
      adsorbed on silica obtained by the sol-gel method influence optical signal
      transmitted by optical fiber. The dependence of optical signal intensity on pH
      was observed. The results of optical measurements are in good agreement with
      those obtained by the potentiometric titration and adsorption of Na+ cations with
      application of a radioactive isotope.

PMID- 16290647
TI  - The role of polycarboxylic acids in calcium phosphate mineralization.
AB  - The role of two polyelectrolytes, poly-L-glutamate and poly-L-aspartate, in the
      growth of calcium phosphate crystal phases, has been investigated at constant
      supersaturation. Both molecules are strong inhibitors of HAP growth when present
      in the solution phase but also act as hydroxyapatite and (octacalcium phosphate)
      like crystal nucleators when adsorbed on germanium surfaces. The structure of the
      polymers in solution is presented and various adsorption models are analyzed. A
      "train-loop" structure of these long, flexible chain polymers on the crystal
      surface is consistent with all the adsorption (experimental and theoretical),
      inhibition, and electrophoretic mobility results.

PMID- 16290649
TI  - The influence of mercury contact angle, surface tension, and retraction mechanism
      on the interpretation of mercury porosimetry data.
AB  - The use of a semi-empirical alternative to the standard Washburn equation for the
      interpretation of raw mercury porosimetry data has been advocated. The
      alternative expression takes account of variations in both mercury contact angle
      and surface tension with pore size, for both advancing and retreating mercury
      meniscii. The semi-empirical equation presented was ultimately derived from
      electron microscopy data, obtained for controlled pore glasses by previous
      workers. It has been found that this equation is also suitable for the
      interpretation of raw data for sol-gel silica spheres. Interpretation of mercury
      porosimetry data using the alternative to the standard Washburn equation was
      found to give rise to pore sizes similar to those obtained from corresponding
      SAXS data. The interpretation of porosimetry data, for both whole and finely
      powdered silica spheres, using the alternative expression has demonstrated that
      the hysteresis and mercury entrapment observed for whole samples does not occur
      for fragmented samples. Therefore, for these materials, the structural hysteresis
      and overall level of mercury entrapment is caused by the macroscopic (>
      approximately 30 microm), and not the microscopic (< approximately 30 microm),
      properties of the porous medium. This finding suggested that mercury porosimetry
      may be used to obtain a statistical characterization of sample macroscopic
      structure similar to that obtained using MRI. In addition, from a comparison of
      the pore size distribution from porosimetry with that obtained using
      complementary nitrogen sorption data, it was found that, even in the absence of
      hysteresis and mercury entrapment, pore shielding effects were still present.
      This observation suggested that the mercury extrusion process does not occur by a
      piston-type retraction mechanism and, therefore, the usual method for the
      application of percolation concepts to mercury retraction is flawed.

PMID- 16290650
TI  - Evaluation of permeability of microporous media, using the modified random
      trajectory approach.
AB  - The random trajectory approach derived recently for the purpose of evaluation of
      the percolation threshold is modified and applied to the modeling of
      permeability. The main modification consists in probabilistic accounting of
      possible trajectories, the total permeability being evaluated as a sum over all
      available percolation trajectories, without any preferences in orientation.
      Results of calculations of permeability vs porosity, sample thickness, and other
      structural factors are presented. It is concluded that the qualitative tendencies
      regarding permeability do not significantly differ from those found before for
      percolation.

PMID- 16290651
TI  - Preparation and structural characterization of activated carbons based on
      polymeric resin.
AB  - In this work, activated carbons (ACs) with high porosity were synthesized from
      polystyrene-based cation-exchangeable resin (PSI) by chemical activation with KOH
      as the activating agent. And the influence of the KOH-to-PSI ratio on the
      porosity of the ACs studied was investigated by using nitrogen adsorption
      isotherms at 77 K and a scanning electron microscope (SEM). As a result, PSI
      could be successfully converted into ACs with well-developed micro- and
      mesopores. The specific surface area and pore volumes increased with an increase
      in the KOH-to-PSI ratio. However, it was found that the addition of KOH did lead
      to the transformation of the micropores to the meso- and macropores. From the
      results of pore size analysis, quite different pore size distributions were
      observed, resulting from the formation of new pores and the widening of the
      existing micropores during KOH activation. A SEM study showed that the resulting
      carbons possessed a well-developed pore structure and the pore size of the ACs
      studied increased with the KOH-to-PSI ratio.

PMID- 16290652
TI  - Condensation of nucleobases at mercury/aqueous solution interface--a structural
      perspective using hydrogen bonding considerations.
AB  - The two-dimensional condensation behavior exhibited by nucleobases at a
      mercury/aqueous solution interface is analyzed on the basis of their hydrogen
      bonded quadruplex structures, and the experimentally observed critical
      temperatures are rationalized incorporating different types of hydrogen bonding,
      surface coordination effects, and stacking considerations. The proposed
      methodology provides a structural basis for the interpretation of critical
      temperatures and enables the calculation of the same pertaining to different
      modified nucleobases. The applicability of the procedure to order-disorder
      transitions of water dipoles at Hg electrodes is also indicated.

PMID- 16290653
TI  - Characterization and metal sorptive properties of oxidized active carbon.
AB  - A commercial activated carbon Chemviron F 400 has been oxidized using nitric acid
      in order to introduce a variety of acidic surface functional groups. Both
      unoxidized and oxidized carbon samples were characterized using nitrogen
      porosimetry, elemental analysis, pH titration, Boehm's titration, and
      electrophoretic mobility measurements. Results show that oxidation treatment
      reduced surface area and pore volume. However, the carbon surface acquires an
      acidic character with carboxylic groups being the dominant surface functional
      groups. The modified sample displays cation-exchange properties over a wide range
      of pH values and exhibits polyfunctional nature. Both carbon samples were
      challenged for the removal of transition metals such as copper(II), nickel(II),
      cobalt(II), zinc(II), and manganese(II). The affinity series
      Mn2+<Co2+<Ni2+<Cu2+>Zn2+ has been found to coincide with the general stability
      sequence of metal complexes (the Irving-Williams series). The higher preference
      displayed by carbons toward copper(II) is a consequence of the fact that
      copper(II) often forms distorted and more stable octahedral complexes.

PMID- 16290654
TI  - Adsorption and association in aqueous solutions of dissymmetric gemini
      surfactant.
AB  - A gemini surfactant with two hydrocarbon chains differing in length and with an
      ethylene spacer N,N-dimethyl-N-(2-(N',N'-dimethyl-N'-dodecylammonio) ethyl)
      tetradecylammonium dibromide, 12-2-14, was synthesized and its physicochemical
      properties were studied by surface tension, conductometry, potentiometry,
      viscosimetry, and light scattering measurements, as well as by optical
      microscopy. Surface properties and thermodynamic parameters lie between those
      obtained for its symmetric counterparts, while association in solution exhibited
      peculiar properties, i.e., high polydispersity and the coexistence of three
      populations of differently sized aggregates.

PMID- 16290656
TI  - A new method of evaluating the average electro-osmotic velocity in microchannels.
AB  - A new and simple method to evaluate the average electro-osmotic flow velocity in
      microchannels is presented in this paper. In this method, the average electro
      osmotic flow velocity is determined by using the slope of the measured current
      time relationship during the electro-osmotic flow of one solution replacing
      another similar solution. The two solutions have the same electrolyte and a small
      difference in ionic concentration. Careful experiments were conducted to measure
      the electrical current change with time during such a displacing process under a
      constant applied electrical field. KCl and LaCl3 electrolyte solutions and 10-cm
      long polyamide-coated silica capillary tubes of 100 and 200 microm in internal
      diameter were used in this study. The average velocities were determined by using
      the slope method. A numerical model was also developed to predict the average
      velocity of such an electro-osmotic flow. An excellent agreement in the average
      velocities between the slope method and the model predictions was found.

PMID- 16290655
TI  - Effects of nonionic micelles on dephosphorylation and aromatic nucleophilic
      substitution.
AB  - Terminal hydroxyl groups of micellized dodecyl (10) and (23) polyoxyethylene
      glycol (C12E10 and C12E23, respectively) are deprotonated by OH-, and the
      alkoxide ions react with 2,4-dinitrochlorobenzene (DNCB) giving ethers, but do
      not react with p-nitrophenyl dimethyl and diethyl phosphate (pNPDMP and pNPDEP,
      respectively), which react wholly with OH-. These substrates have similar
      hydrophobicities and should locate similarly in the micellar interfacial regions.
      These differences in reactivities are due to differences in relative
      nucleophilicities of OH- and alkoxide ions in aromatic nucleophilic substitution
      and dephosphorylation in micelles. Reactivities of DNCB and the related ethers
      indicate that local concentrations of OH- are similar in the aqueous and micellar
      interfacial regions but those of the alkoxide ions are higher in C12E10 than in
      C12E23 micelles due to differences in the molar volumes of the interfacial
      regions. With time the initially formed ethers react at similar rates with OH-
      generating 2,4-dinitrophenoxide ion.

PMID- 16290657
TI  - Effects of poloxamer polydispersity on micellization in water.
AB  - The poloxamer 284 (Pluronic P94) is a triblock copolymer of poly(ethylene oxide)
      and poly(propylene oxide). P94 and fractions of P94 obtained after centrifugation
      at temperatures where solutions contain both dissolved unimers and micelles have
      been investigated by differential scanning calorimetry, mass spectrometry, and
      NMR. The results show that the P94 sample is heterogeneous with respect to both
      chemical composition and molar mass. The first micelles formed, when the
      temperature is increased, contain poloxamers with a significantly higher
      propylene oxide content and a higher molar mass in agreement with theoretical
      predictions. The characteristic temperatures of micellization, sphere-to-rod, and
      phase separation transitions observed in thermograms are influenced by
      polydispersity, which results in broader transitions.

PMID- 16290658
TI  - Effect of glass fiber surface treatments on mechanical strength of epoxy based
      composite materials.
AB  - Sizing glass fibers with silane coupling agents enhances the adhesion and the
      durability of the fiber/polymer matrix interface in composite materials. There
      are several tests to determine the interfacial strength between a fiber and
      resin, but all of them present difficulties in interpreting the results and/or
      sample preparation. In this study, we observed the influence of different
      aminosilanes fiber coatings on the resistance of epoxy-based composite materials
      using a very easy fractographic test. In addition, we tried a new fluorescence
      method to get information on a molecular level precisely at the interface.
      Strength was taken into account from two standpoints: (i) mechanical strength and
      (ii) the resistance to hydrolysis of the interface in oriented glass-reinforced
      epoxy-based composites. Three silanes: gamma-aminopropyltriethoxysilane, gamma
      Aminopropylmethyldiethoxysilane, and gamma-Aminopropyldimethylethoxysilane were
      used to obtain different molecular structures at the interface. It was concluded
      that: (i) the more accessible amine groups are, the higher the interface rigidity
      is; (ii) an interpenetrating network mechanism seems to be the most important for
      adhesion and therefore to the interfacial strength; and (iii) the higher the
      degree of crosslinking in the silane coupling layer is, the higher the hydrolytic
      damage rate is.

PMID- 16290659
TI  - Organoclay sorption of benzene as a function of total organic carbon content.
AB  - The sorption of benzene to bentonite, activated carbon, and two organo-clays
      synthesized with the quaternary ammonium organic cations
      hexadecyltrimethylammonium (HDTMA) and benzyltriethylammonium (BTEA) was
      quantified as a function of total organic carbon content. The unmodified
      bentonite sorbed no benzene, while the activated carbon exhibited the strongest
      benzene uptake. For the organoclays, organic cations were exchanged onto Wyoming
      bentonite at four different percentages of the clay's cation exchange capacity.
      For HDTMA clay, in which partitioning is the dominant sorptive medium, it was
      determined that benzene sorption increased as the total organic carbon content
      increased (as the clay became more hydrophobic). In contrast, the sorption of
      benzene to BTEA clay, an adsorptive clay, decreased as the total organic carbon
      content of the clay was increased. It is believed that the sorptive capacity of
      BTEA clay decreases due to the formation of positively charged dimers on the
      clay's surface that block access to the sorptive sites. The organoclays sorbed
      more benzene than the unmodified bentonite, but less than the activated carbon.

PMID- 16290660
TI  - The determination of the free energy of an electrical double layer.
AB  - A well-known charging process is used to obtain the free energy of an electrical
      double layer, in which the double layer is built up by a transfer of ions from
      one phase to another. The present study formulates proofs that this charging
      process cannot determine the free energy of an electrical double layer.

PMID- 16290662
TI  - On the acid-base chemistry of the Keggin polymers: GaAl12 and GeAl12.
AB  - The acid-base properties of GaAl12 and GeAl12 molecules have been investigated
      and compared to those of the Al13 molecule using alkalimetric titration at two
      concentrations of the Keggin complex. As in the case of Al13, the positive charge
      of both GaAl13 and GeAl12 is entirely lost within half a pH unit if the
      concentration of the Keggin molecules is low (1.25 microM). We find that GeAl12
      is significantly more acidic than either the GaAl12 or the Al13 molecules. As
      positive charge is removed from the Keggin complexes by deprotonation, they tend
      to aggregate, resulting in titration curves that flatten out at higher Z values.
      Molecule-molecule interactions appear to be more distinct at elevated
      concentrations of the Keggin complexes (12.5 microM).

PMID- 16290661
TI  - The influence of stern layer conductance on the dielectrophoretic behavior of
      latex nanospheres.
AB  - The influence of the Stern layer conductance on the dielectrophoretic behavior of
      sub-micrometer-sized latex spheres is examined. The dielectrophoretic response of
      the particles is measured and analyzed in terms of a model of surface conductance
      divided into discrete components related to the structure of the double layer.
      The effect of both co- and counterions in the bulk solution on the Stern layer
      conductance is demonstrated.

PMID- 16290663
TI  - Adsorption and direct probing of fibrinogen and sodium myristate at the air/water
      interface.
AB  - Fibrinogen (FB), a serum protein, is considered a major inhibitor of lung
      surfactant function at the lining layer of the alveoli. In this study, the
      adsorption of aqueous bovine FB at the air/water interface was investigated with
      tensiometry and directly probed for the first time with ellipsometry and infrared
      reflection adsorption spectroscopy (IRRAS). The tension results show that FB has
      moderate surface activity. The surface densities of FB were calculated by using
      two different ellipsometry models to range from 3+/-0.2 to 17+/-2 mg/m2, for 7.5
      to 750 ppm of FB in water at 25 degrees C. Although FB at concentrations from 75
      to 750 ppm reached about the same steady surface tension value, the surface
      densities at 750 ppm FB were substantially larger. The same techniques were used
      for studying aqueous mixtures of 7.5 to 750 ppm FB with 2 mM of sodium myristate
      (SM) to investigate a possible interaction of the SM with the protein. The
      behavior of the FB/SM mixtures was found to be close to that of SM alone. The
      surface tension of the FB/SM mixtures reached values less than 10 mN/m under
      surface area oscillation at 20 or 80 rpm. These results and the ellipsometry and
      the IRRAS results indicate that at a concentration of 2 mM SM, FB, up to 750 ppm,
      does not inhibit the surfactant surface-tension-lowering function. In certain
      cases the results demonstrate that FB and SM may act cooperatively in lowering
      the surface tension.

PMID- 16290664
TI  - Preparation and characterization of hollow spheres of rutile.
AB  - Hollow spherical particles of rutile were obtained by coating colloidal
      polystyrene beads with a titanium oxide hydrate layer and subsequently calcining
      at elevated temperatures under an oxygen atmosphere. In order to investigate the
      optimum conditions for the preparation of these hollow beads the maximum
      temperature and heating rate were systematically varied. The dimensions of the
      voids and the shell thickness of the hollow beads can be tailored by the size of
      the polystyrene beads and the thickness of the inorganic layer, respectively.

PMID- 16290665
TI  - Low temperature synthesis and characterization of porous anatase TiO2
      nanoparticles.
AB  - An ethanol solution of Ti-peroxy compounds was prepared from the ethanol solution
      of titanium isopropoxide (Ti(O-iPr)4) and H2O2. Heating of the ethanol solution
      of the Ti-peroxy compounds at 348 K formed a Ti-peroxy gel, and heat treatment of
      the gel at 348 K for more than 6 h formed gels that consisted of anatase
      nanoparticles. The diameter of the anatase nanoparticles increased from 9 to 15
      nm as the heating time increased from 6 to 48 h. According to the results of the
      N2 adsorption measurement, the anatase nanoparticles had micropores, and the
      specific surface area (SBET) was in the range of 254 to 438 m2/g. The particle
      size, lattice strain, specific surface area, and photocatalytic activity of the
      anatase nanoparticles can be regulated by the heating time of the Ti-peroxy gel
      at 348 K.

PMID- 16290666
TI  - Dielectrophoretic behavior of latex nanospheres: low-frequency dispersion.
AB  - The electrostatic manipulation of nanoparticles using nonuniform electric fields
      (dielectrophoresis) has proved a useful method of investigating the movement of
      charge around colloidal particles. While previous work has explained many of the
      ways in which particle behavior deviates from that predicted by classical Maxwell
      Wagner interfacial polarization theory, there exists an additional, anomalous
      polarization mechanism observed in media of high conductivity, causing an
      unexpected observation of positive dielectrophoresis. Here this is suggested that
      this may be explained in terms of the polarization of the Stern layer.

PMID- 16290667
TI  - Surface layers of 6-thioguanine on the mercury electrode.
AB  - The adsorption behavior of 6-thioguanine (6TG) on a hanging mercury drop
      electrode has been studied with ac and cyclic voltammetry in 0.1 M Na2SO4 and
      0.01 M sodium acetate solutions at pH 4.3. Several condensed phases of chemically
      adsorbed 6TG as well as one phase of physically adsorbed 6TG have been
      characterized. Under total coverage conditions, the films of chemiadsorbed
      molecules inhibit rather efficiently the electrode reaction of mercury oxide
      formation.

PMID- 16290668
TI  - Atomic force microscopy and magnetic force microscopy study of model colloids.
AB  - Atomic force microscopy (AFM) is used to study the size, shape, and
      polydispersity of a variety of magnetic and nonmagnetic model colloids,
      previously imaged by transmission electron microscopy (TEM) only. Both height and
      phase images are analyzed and special attention is given to 3D morphology and
      softness of particles, as well as structures and presence of secondary components
      in the colloid, difficult to investigate with TEM. Several methods of tip
      characterization followed by deconvolution were applied in order to improve the
      accuracy of lateral diameter determination. In the case of magnetite particles
      dispersed in conventional ferrofluids, we explore both experimentally and
      theoretically the possibility of using magnetic force microscopy (MFM). We
      propose and discuss several models which allow to estimate the magnetic moment of
      a single domain superparamagnetic sphere using MFM, which cannot be done with
      other techniques; alternatively the tip magnetization can be determined.

PMID- 16290669
TI  - Dynamic and static interactions between bitumen droplets in water.
AB  - In the commercial bitumen extraction operation, dynamic and static interaction
      forces between bitumen drops in water determine the likelihood of desirable
      bitumen coalescence at different process stages. These dynamic and static forces
      were measured using colloidal particle scattering and hydrodynamic force balance
      techniques, respectively. In the former technique, dynamic interactions are
      studied through droplet-droplet collision trajectory measurement. In the latter
      technique, the static attractive forces between droplets are determined when a
      doublet is separated with a known and adjustable hydrodynamic force. The dynamic
      force measurement implies the presence of rigid chains on bitumen surfaces. The
      mean chain lengths for deasphalted bitumen at pH 7, whole bitumen at pH 7, and
      whole bitumen at pH 8.5 are 50, 78, and 41 nm, respectively. However, the static
      force measurement indicates much shorter mean chain lengths (<9 nm) in these
      three bitumen systems. Shorter chain length indicates weaker repulsive force.
      This finding of a much weaker repulsion between bitumen droplets under static
      conditions has important implications on the commercial bitumen extraction
      operation.

PMID- 16290670
TI  - Dynamic electrophoretic mobility of a concentrated dispersion of particles with a
      charge-regulated surface at arbitrary potential.
AB  - The dynamic electrophoretic mobility of a concentrated dispersion of biocolloids
      such as cells and microorganisms is modeled theoretically. Here, a biological
      particle is simulated by a particle, the surface of which contains dissociable
      functional groups. The results derived provide basic theory for the
      quantification of the surface properties of a biocolloid through an
      electroacoustic device, which has the merit of making direct measurement on a
      concentrated dispersion without dilution. Two key parameters are defined to
      characterize the phenomenon under consideration: the first, A, is associated with
      the pH of the dispersion, and the second, B, is associated with the equilibrium
      constant of the dissociation reaction of the functional group. We show that if A
      is large and/or B is small, the surface potential is high, and the effect of
      double-layer polarization becomes significant. In this case the dynamic
      electrophoretic mobility may have a local maximum and a phase lead as the
      frequency of the applied electric field varies. Due to the hydrodynamic
      interaction between neighboring particles, the dynamic electrophoretic mobility
      decreases with the concentration of dispersion.

PMID- 16290671
TI  - Influence of electrical double-layer interaction on coal flotation.
AB  - In the early 1930s it was first reported that inorganic electrolytes enhance the
      floatability of coal and naturally hydrophobic minerals. To date, explanations of
      coal flotation in electrolytes have not been entirely clear. This research
      investigated the floatability of coal in NaCl and MgCl2 solutions using a
      modified Hallimond tube to examine the role of the electrical double-layer
      interaction between bubbles and particles. Flotation of coal was highly dependent
      on changes in solution pH, type of electrolyte, and electrolyte concentration.
      Floatability of coal in electrolyte solutions was seen not to be entirely
      controlled by the electrical double-layer interaction. Coal flotation in low
      electrolyte concentration solutions decreases with increase in concentration, not
      expected from the theory since the electrical double layer is compressed,
      resulting in diminishing the (electrical double layer) repulsion between the
      bubble and the coal particles. Unlike in low electrolyte concentration solutions,
      coal flotation in high electrolyte concentration solutions increases with
      increase in electrolyte concentration. Again, this behavior of coal flotation in
      high electrolyte concentration solutions cannot be quantitatively explained using
      the electrical double-layer interaction. Possible mechanisms are discussed in
      terms of the bubston (i.e., bubble stabilized by ions) phenomenon, which explains
      the existence of the submicron gas bubbles on the hydrophobic coal surface.

PMID- 16290672
TI  - Instability for shearing of an electrified Kelvin fluid sheet with or without
      supporting surface charges.
AB  - The present study demonstrates the instability of streaming in a fluid layer
      sandwiched between two other bounded fluids under the influence of a vertical
      periodic electric field. The fluids are of a viscoelastic nature where the
      constitutive equation is Kelvin type. Due to the inclusion of streaming flow and
      the influence of a periodic force, a mathematical simplification is urged.
      Equation of motion is solved in light of the weakness effect for the viscoelastic
      properties. The instabilization of the problem is examined in view of the
      linearization of the perturbation approach. The boundary value problem is
      discussed for a charged or uncharged fluid sheet. Both cases are lead to derive
      linear coupled Mathieu equations with complex coefficients and damping terms.
      Stability analysis is discussed through a simplified configuration for the system
      of Mathieu equations. It is found that the elasticity parameters as well as the
      viscosity parameters have a stabilizing influence. The field frequency plays a
      destabilizing role in the presence of surface charges and a dual role in the
      absence of surface charges. The presence of surface charges retards the
      stabilizing influence of the viscoelastic effects. This calculation shows that
      the fluid velocity retards the destabilizing influence for the electric field.
      The increase of the thickness of the fluid sheet plays two different roles. A
      stabilizing role in the presence of surface charges and a destabilizing influence
      in their absence.

PMID- 16290673
TI  - A structural study of amphiphilic PAMAM (poly(amido amine)) dendrimers in
      Langmuir and Langmuir-Blodgett films.
AB  - Two amphiphilic PAMAM dendrimers are synthesized by attaching 12
      hydroxydodecanoic acid (HA) chains to a poly(amido amine) (PAMAM) dendrimer core
      (including generation I and generation II). The limiting molecular area obtained
      from the surface pressure-area isotherm at the air/water interface suggests the
      edge-on configuration for both dendrimers in Langmuir films. The edge-on
      arrangement is also supported by the atomic force microscopic (AFM) studies of
      the Langmuir-Blodgett films.

PMID- 16290674
TI  - Zeta potential of stearic acid monolayer at the air-aqueous solution interface.
AB  - The zeta (zeta) potential of an insoluble monolayer of stearic acid at the air
      water interface was measured as a function of pH in the presence of 0.0001,
      0.001, and 0.01 M NH4NO3. The zeta potential was measured by means of the plane
      interface technique which involved the determination of the electrophoretic
      velocity profile of reference (polystyrene latex) particles along the solution
      depth in a rectangular open quartz cell. The zeta vs pH relationship at 0.001 and
      0.01 M NH4NO3 was analyzed in terms of the Gouy-Chapman-Stern-Grahame model for
      electrical double-layer incorporating a simple site-binding model used previously
      for many oxide and latex colloid studies. The dissociation constant (pKa) of
      stearic acid monolayer and double-layer parameters such as integral capacitances
      of inner and outer Helmholtz layers and the complexation constant of counterion
      complexes were also estimated.

PMID- 16290675
TI  - Effect of structural stress on the intercalation rate of kaolinite.
AB  - Particle size in kaolinite intercalation showed an inverse reactivity trend
      compared with most chemical reactions: finer particles had lower reactivity and
      some of the fine particles cannot be intercalated. Although this phenomenon was
      noted in the early 1960s and several hypotheses have been reported, there is no
      widely accepted theory about the unusual particle size response in the
      intercalation. We propose that structural stress is a controlling factor in the
      intercalation and the stress contributes to the higher reactivity of the coarser
      particles. In this study, we checked the structural deformation spectroscopically
      and indirectly proved the structural stress hypothesis. A Georgia kaolinite was
      separated into nine size fractions and their intercalations by hydrazine
      monohydrate and potassium acetate were investigated with X-ray diffraction (XRD)
      and Fourier-transform infrared (FTIR) analyses. The apical Si-O band of kaolinite
      at 1115 cm(-1) shifted to 1124 cm(-1) when the mineral was intercalated to 1.03
      nm by hydrazine monohydrate, and its strong pleochroic properties became much
      weaker. Similar reduction in pleochroism was observed on the surface OH bands of
      kaolinite after intercalation. Both the bending vibrations of the inner OH group
      at 914 cm(-1) and of the surface OH group at 937 cm(-1) shifted to 903 cm(-1)
      after intercalation by hydrazine. A new band for the inner OH group appeared at
      3611 cm(-1) during the deintercalation of the 1.03 nm hydrazine kaolinite
      complex. Pleochroism change in the apical Si-O band suggested the tetrahedra had
      increased tilt with respect to the (001) plane. The tilt of the Si-O apical bond
      could occur only if the octahedra had also undergone structural rearrangement
      during intercalation. These changes in the octahedral and tetrahedral sheets
      represent some change in the manner of compensation for the structural misfit of
      the tetrahedral sheet and octahedral sheet. As the lateral dimensions of a
      kaolinite particle increases, the cumulative degree of misfit increases.
      Intercalation breaks the hydrogen bonds between layers and allows for the
      structure to reduce the accumulated stress in some other manner. The reversed
      size effect on intercalation probably was not caused by crystallinity differences
      as reported in the literature, because the Hinckley and Lietard crystallinity
      indices of the four clay fractions were very close to each other. Impurities,
      such as dickite- or nacrite-like phases are not significant in the studied sample
      as suggested by the XRD and IR results, they are not the main reasons for the
      lower reactivity of the finer particles.

PMID- 16290676
TI  - Effect of pore structure on surface characteristics of zirconium phosphate
      modified silica.
AB  - Three samples of silica of different pore structure-predominantly microporous,
      S1; mesoporous, S2; and nonporous, S3-were modified with zirconium phosphate and
      examined. Pore structure analysis showed that modification had taken place in
      wider pores of S1 leaving a totally microporous sample, and in large pores of S2
      giving a mesoporous sample of narrower pore size distribution. The modification
      of the nonporous sample decreased the surface area and pore volume to a lower
      extent than in the other two samples, but resulted in a surface of lower energy
      toward N2. The different distribution of surface silanol groups on the surfaces
      of different porosity may result in variable pictures on the modified surfaces as
      reflected in the differences observed in Bronsted acidity of modified surfaces.
      The use of these modified silica samples for amino acid adsorption (L-glutamic
      acid and L-alanine) indicated that both the isoelectric point of the amino acid
      and the distribution of surface groups on modified solids are controlling the
      adsorption process.

PMID- 16290677
TI  - Advective flow and floc permeability.
AB  - This work monitored advection flow through a floc by bubble tracking. Close
      examination of the motion of a swarm of hydrogen bubbles that passed over a free
      falling floc allowed the extent of advection flow to be estimated at 53% for the
      original activated sludge floc, and 12% for the flocculated floc. The interior
      permeability of the sludge flocs was estimated from this information. The fluid
      force exerted on the falling floc was also considered.

PMID- 16290678
TI  - Removal of proteinaceous soils using hydroxyl radicals generated by the
      electrolysis of hydrogen peroxide.
AB  - We have developed here for the first time a novel method to generate hydroxyl
      radicals, *OH, by applying slightly negative electric potentials (-0.2--0.8 V vs
      Ag/AgCl) to the surface of a metal (or metal oxide) that is in contact with
      hydrogen peroxide solution containing a supporting electrolyte. Namely, *OH
      radicals were generated at the surface by the electrolysis of hydrogen peroxide
      according to the equation, H2O2+e- --> *OH+OH-. This method was used to clean a
      stainless steel fouled with a model protein, beta-lactoglobulin. The *OHs
      generated at the surface were effective in removing beta-lactoglobulin that had
      been irreversibly adsorbed, by several minutes of treatment at room temperature
      (22+/-2 degrees C). The removal rates measured for various concentrations of H2O2
      and supporting electrolyte and different potentials were determined exclusively
      by the electric current.

PMID- 16290679
TI  - Analytical approach for the Lucas-Washburn equation.
AB  - Porous media can be characterized by studying the kinetics of liquid rise within
      the pore spaces. Although porous media generally have a complex structure, they
      can be modeled as a single, vertical capillary or as an assembly of such
      capillaries. The main difficulties lie in separately estimating the effective
      mean radius of the capillaries and the contact angle between the liquid and the
      pore. In this paper we circumvent these obstacles by exploring another approach
      and suggest an analytical approach of the classical Lucas-Washburn equation
      (LWE). Specifically, we consider that the contact angle between the liquid
      meniscus and the inner surface of the capillary becomes a dynamic contact angle
      when the liquid front is in movement. It has previously been demonstrated that
      the resulting time dependence is due to frictional dissipation at the moving
      wetting front.

PMID- 16290680
TI  - Numerical simulations of capillary-driven flows in nonuniform cross-sectional
      capillaries.
AB  - In this study the wetting behavior of converging-diverging and diverging
      converging capillaries is investigated numerically using an in-house written,
      finite-element code. An interface tracking procedure based on the predicted
      change in the total liquid volume, to update the interface location, and Cox's
      formulation, to determine the dynamic contact angle and the interface shape, is
      proposed and used. Flow simulations revealed that both converging-diverging and
      diverging-converging capillaries exhibit significantly slower wetting behavior
      than straight capillaries and that any deviation in the capillary diameter
      necessarily tends to slow the overall wetting speed. This behavior was attributed
      to local regions of very low capillary pressure and high viscous retardation
      force when the capillary diameter at the interface was significantly larger than
      the capillary diameter over the upstream fluid. Though the local wetting
      velocities were different, when equivalent capillaries were compared it was found
      that both converging-diverging and diverging-converging capillaries had the same
      total fill time independent of the number of irregular regions, suggesting that
      the simple model is sufficient for predicting the overall effect. The influence
      of surface tension and contact angle on the total wetting time was found to be
      similar for both straight and irregularly shaped capillaries.

PMID- 16290681
TI  - Thermodynamic quantities of surface formation of aqueous electrolyte solutions.
      V. Aqueous solutions of aliphatic amino acids.
AB  - The surface tension of aqueous solutions of glycine, L-alanine, L-valine, and L
      leucine has been observed using the drop volume method as a function of
      temperature and concentration. The L-leucine molecules form an adsorbed film,
      while glycine affects the water surface in accordance with simple salts which
      dissociate into cations and anions completely. The surface tension data have been
      analyzed in view of K. Motomura's thermodynamic treatment (J. Colloid Interface
      Sci.64, 348 (1978)), and the thermodynamic quantities relevant to the surface
      have been shown systematically.

PMID- 16290682
TI  - Thermodynamics of micellization of alkyldimethylbenzylammonium chlorides in
      aqueous solutions.
AB  - Specific conductivities of alkyldimethylbenzylammonium chlorides (alkyl=decyl-,
      dodecyl-, tetradecyl-, and hexadecyl-) in aqueous solutions were measured as a
      function of molality and temperature. Critical micelle molalities (cmc) and
      degrees of ionization of the micelles, beta, were estimated from the dependence
      of the specific conductivity on molality. It was found that temperature
      dependence of cmc is U-shaped with a minimum shifting toward higher temperatures
      with a decrease in the chain length of the alkyl group. The temperature
      dependence of ln xcmc (where xcmc is the cmc in mole fraction units) was fitted
      to the equation of Muller, which we modified by taking into account the
      temperature dependencies both of beta and of change in heat capacity upon
      micellization. From the fitting parameters, Gibbs free energies, enthalpies, and
      entropies of micellization as a function of temperature were estimated.

PMID- 16290683
TI  - Multiple emulsion stability: pressure balance and interfacial film strength.
AB  - The objective of this study was to investigate the significance of inner and
      outer phase pressure, as well as interfacial film strength on W/O/W multiple
      emulsion stability using microscopy and long-term stability tests. It was
      observed that immediately upon applying a coverslip to samples the multiple
      droplets deformed and there was coalescence of the inner aqueous droplets. Under
      certain conditions (such as lipophilic surfactant concentration and internal
      phase osmotic pressure) the destabilized multiple emulsions formed unique
      metastable structures that had a "dimpled" appearance. The formation of these
      metastable structures correlated with the real-time instability of the W/O/W
      multiple emulsions investigated. Multiple emulsion stability also correlated with
      the interfacial film strength (measured by interfacial elasticity) of the
      hydrophobic surfactant at the mineral oil/external continuous aqueous phase
      interface. The formation of the metastable dimpled structures and the long-term
      stability of the multiple emulsions were dependent on the osmotic pressure of the
      inner droplets and the Laplace curvature pressure as described by the Walstra
      Equation (P. Walstra, "Encyclopedia of Emulsion Technology" (P. Becher, Ed.),
      Vol. 4. Dekker, New York, 1996). It appears that the effect of coverslip pressure
      on multiple emulsions may be useful as an accelerated stability testing method or
      for initial formulation screening.

PMID- 16290684
TI  - An empirical kinetic model for the gelation of a concentrated latex suspension in
      the presence of nonadsorbing polymer chains.
AB  - An empirical model has been proposed to describe the kinetic aspect of the
      gelation process of a concentrated latex mixture in the presence of nonadsorbing
      polymer chains. It was found to allow the identification of two predominant
      effects, a viscosity effect and an excluded volume one effect that balance during
      gelation, and to predict the polymer volume fraction for which the transition
      between these two predominant effects occurs in the dilute polymer concentration
      range.

PMID- 16290685
TI  - Hydrodynamic interaction between spheres coated with deformable thin liquid
      films.
AB  - In this article, we considered the hydrodynamic interaction between two unequal
      spheres coated with thin deformable liquids in the asymptotic lubrication regime.
      This problem is a prototype model for drop coalescence through the so-called
      "film drainage" mechanism, in which the hydrodynamic contribution comes
      dominantly from the lubrication region apart from the van der Waals interaction
      force. First, a general formulation was derived for two unequal coated spheres
      that experienced a head-to-head collision at a very close proximity. The
      resulting set of the evolution equations for the deforming film shapes and stress
      distributions was solved numerically. The film shapes and hydrodynamic
      interaction forces were determined as functions of the separation distance, film
      thickness, viscosity ratios, and capillary numbers. The results show that as the
      two spheres approach each other, the films begin to flatten and eventually to
      form negative curvature (or a broad dimple) at their forehead areas in which high
      lubrication pressure is formed. The dimple formation occurs earlier as the
      capillary number increases. For large capillary numbers, the film liquids are
      drained out from their forehead areas and the coated liquid films rupture before
      the two films "touch" each other. Meanwhile, for small capillary numbers, the gap
      liquid is drained out first and the two liquid films eventually coalesce.

PMID- 16290687
TI  - Site percolation model for latex film formation in soft polymer matrix.
AB  - The UV-visible (UVV) technique was used to monitor latex film formation in a soft
      polymer matrix. Various film samples were prepared by increasing the amount of
      poly(methyl methacrylate) (PMMA) particles in a poly(isobutylene) (PIB) matrix.
      These samples were then annealed above the glass transition temperature to
      promote latex film formation. Transmitted photon intensities, Itr, were measured
      for each film. It is observed that Itr decrease as the latex content is
      increased, which was explained by the increase in scattered light intensity, Isc.
      The drastic increase in Isc above a certain latex content is attributed to the
      site percolation of latex particles in the PIB matrix. The percolation threshold
      and the critical exponent were measured and found to be 0.3 and 0.4,
      respectively. The increase in Itr by annealing of film samples above Tg was
      explained with the void closure process below 0.8 occupation probability. When
      the film is occupied completely with the latex particles, interdiffusion of
      polymer chains was observed. Viscous flow and chain diffusion activation energies
      were determined and found to be 8 and 51 kcal/mol, respectively.

PMID- 16290686
TI  - Flow of water through channels filled with deformable polymer gels.
AB  - A mathematical model is developed for the flow of water through a channel
      impregnated with a polymer gel that is treated as an elastic and deformable
      porous medium. The model uses a Brinkman equation along with an experimentally
      observed velocity-dependent permeability. Numerical and approximate analytical
      solutions are given. These results show that the gel intrinsic properties, i.e.,
      gel reference permeability and elastic index, control the water flow. First, the
      permeability of water flow through the gel increases with an increase of gel
      reference permeability. Second, the velocity of water decreases when the gel
      velocity exponent increases. Our theoretical results show that the velocity
      dependent permeability of water flow through polymer gels is in fact an intrinsic
      property of the gel rather than a property of the channel or some interaction
      between the gel and the pore walls.

PMID- 16290688
TI  - Adsorption of polyacrylic acid and its copolymers with acrylonitrile on zinc
      oxide particles.
AB  - Adsorption of polyacrylic acid and its copolymers with acrylonitrile, containing
      different quantities of carboxyl groups, on the dispersion of zinc oxide was
      investigated. The kinetics of polymer desorption was investigated based on data
      concerning the change in concentration of free carboxylic groups of polymer and
      zinc ions in solution. The concentration of free carboxyl groups decreases and
      the concentration of zinc ions in the liquid phase above the residue after
      separation of zinc oxide particles increases with time, reaching a constant
      value. The dependence of the concentration of free carboxyl groups and zinc ions
      in the liquid phase on the initial concentration of polymer in the plateau
      section of the kinetic curve was investigated. Adsorption isotherms of copolymers
      depend on their solubility in water and can be described by different
      mathematical models.

PMID- 16290689
TI  - Novel sintering behavior of polystyrene nanolatex particles in the filming
      process.
AB  - The filming process of polystyrene nanolatex (NPS) particles was studied by a
      combination of various methods. For a constant annealing time of 1 h, the AFM
      images showed that the deformation and interdiffusion temperatures of NPS
      particles were ca. 90 and 100-110 degrees C, respectively. In spin-lattice
      relaxation measurements of solid state NMR, it is found that T1L, T1S, and PL
      increased significantly after annealing at 90 and 100 degrees C for 1 h. DSC
      results showed that there was a exothermic peak near Tg after annealing for 1 h
      at the elected temperatures below 95 degrees C; otherwise, the exothermic peak
      disappeared after annealing at 100 degrees C or above. The apparent density of
      NPS increased suddenly in the temperature range of 90-110 degrees C. The results
      indicated that the macromolecules are highly constrained in NPS particles,
      leading to higher conformational energy, with more free volume and segments less
      restricted, which are the driving forces for the particles sintering at a lower
      temperature compared to the micro-PS particles with larger diameter.

PMID- 16290690
TI  - Accounting for diffuse layer ions in triple-layer models.
AB  - The triple-layer model is one of the most widely used surface complexation models
      for adsorption on mineral surfaces. In current implementations, the accounting of
      ions in the diffuse layer may be neglected, resulting in a charge imbalance in
      the modeled solution as well as errors in mass balance, particularly in low ionic
      strength solutions when mineral-specific surface area is large. This paper
      introduces an internally consistent scheme for modeling diffuse layer ions in the
      triple-layer model. Model calculations illustrate the difference between the
      proposed and previous implementations using an idealized example. The guarantee
      of charge balance on both sides of the interface assures that pH is accurately
      modeled. This may be important in reactive transport simulations, such as
      modeling adsorption in low ionic strength variable charge soil solutions.

PMID- 16290691
TI  - Dynamic surface tension and its diffusional decay of dodecyl ethoxylates with
      different homologue distribution.
AB  - Dynamic surface tension and its diffusional decay have been studied with four
      different polydisperse C12E7 at different temperatures and different
      concentrations. The CMC and the headgroup area from equilibrium surface tension
      were shown with polydispersity and temperature. The chain length of oxyethylene
      on the surface was derived from comparison between the headgroup area of
      monodisperse dodecyl ethoxylates and that of polydisperse C12E7. The values for
      (Deff/D) were deduced with a diffusion-controlled adsorption model using
      parameters obtained from equilibrium surface tension. It was shown at short
      adsorption time that molecules were really adsorbed onto the surface in a
      diffusion-controlled manner. At a comparably long adsorption time, the ratios
      (Deff/D) were calculated by assuming the selective adsorption onto the surface.
      The modified Arrhenius-type equation was proposed by putting a concentration term
      in front of the exponential terms. The modified Arrhenius-type equation gave
      Ea=30 kJ/mole for this system. Ea directly derived without an Arrhenius plot was
      between 9 to 11 kJ/mole. It was an indication that the activation energy alone
      was not enough to explain the decay of dynamic surface tensions.

PMID- 16290692
TI  - Preparation of finely dispersed drugs. III. Cyclosporine.
AB  - Two different precipitation processes are described, which produced dispersions
      of spherical particles of cyclosporine ranging in diameter from approximately 10
      nm to several micrometers. This drug is of interest for its immunosuppressive
      activity in the antirejection of transplanted organs. The effects of several
      experimental parameters on the average particles size and uniformity have been
      investigated. Aging of spherical particles resulted in large crystalline-type
      aggregates.

PMID- 16290693
TI  - Ionic rectification properties of a bipolar interface consisting of a cationic
      surfactant and cation-exchange membrane.
AB  - A novel bipolar interface that consists of cationic surfactant and cation
      exchange membrane was successfully prepared in an aqueous electrolyte system.
      This bipolar interface shows a ionic rectification behavior similar to that
      observed in bipolar membranes. However, different from bipolar membranes, this
      system has a total rectification behavior, where we cannot observe the occurrence
      of a water-splitting phenomenon, which always occurs in the bipolar membrane
      process under reverse bias conditions.

PMID- 16290695
TI  - A correlation for establishing solvolysis rates of aqueous Al(III) complexes: a
      possible strategy for colloids and nanoparticles.
AB  - We here examine whether rates of solvolysis for a range of aluminum complexes can
      be predicted semiempirically by correlating calculated values of Al-O bond
      lengths with rate coefficients. We focus on a series of mono- and bis-ligated
      aqueous aluminum monomers and three epsilon-Keggin-like aluminum polyoxocations,
      and we make no attempt to simulate transition states. The Al-O bond lengths were
      calculated by performing ab initio geometry optimizations using the polarizable
      continuum model to estimate solvation effects. Both Hartree-Fock and density
      functional methods (B3LYP) were tested using several basis sets up to 6-31+G(d).
      We find a strong correlation between rate coefficients for mono-ligated aluminum
      monomers and bond lengths to hydration waters. We cannot extrapolate the
      correlation, however, to large epsilon-Keggin-like multimers or to bis-ligated
      complexes, which suggests that the activated equilibrium for exchange of a water
      molecule in these molecules is different than that in the simple monomers.

PMID- 16290696
TI  - An inverse gas chromatography study of the adsorption of organics on nickel- and
      copper-hexacyanoferrates at zero surface coverage.
AB  - The surface properties of Ni and Cu hexacyanoferrates were investigated by the
      inverse gas chromatography method. Retentions of 10 organic compounds were
      measured at zero surface coverage in the temperature range 80 to 95 degrees C.
      The gas/solid partition coefficients and the related thermodynamic data of
      adsorption (standard free energy change, standard state enthalpies, and entropy
      changes) also at zero surface coverage were determined. The dispersive component
      of free surface energy of both hexacyanoferrates, at investigated temperatures,
      was calculated. The surface acid/base properties were also evaluated using polar
      adsorbates and the results obtained indicate that nickel hexacyanoferrate is more
      acidic than copper hexacyanoferrate.

PMID- 16290697
TI  - Adsorption relaxation for nonionic surfactants under mixed barrier-diffusion and
      micellization-diffusion control.
AB  - Relaxation processes of surfactant adsorption and surface tension, which are
      characterized by two specific relaxation times, are theoretically investigated.
      We are dealing with fluid interfaces and small initial deviations from
      equilibrium. For surfactant concentrations below the critical micellization
      concentration (CMC), we consider adsorption under mixed barrier-diffusion
      control. General analytical expressions are derived, which are convenient for
      both numerical computations and asymptotic analysis. Series expansions for the
      short- and long-time limit are derived. The results imply that the short-time
      asymptotics is controlled by the adsorption barrier, whereas the long-time
      asymptotics is always dominated by diffusion. Furthermore, for surfactant
      concentrations above the CMC, adsorption under mixed micellization-diffusion
      control is considered. Again, a general analytical expression is derived for the
      relaxation of surfactant adsorption and surface tension, whose long- and short
      time asymptotics are deduced. The derived equations show that at the short times
      the relaxation is completely controlled by the diffusion, whereas the long-time
      asymptotics is affected by both demicellization and diffusion. The micellar
      effect is manifested as an exponential (rather than square-root) decay of the
      perturbation. The derived expressions are applied to process available
      experimental data for the nonionic surfactant Triton X-100 and to determine the
      respective demicellization rate constant.

PMID- 16290698
TI  - Studies on Mg/Fe hydrotalcite-like-compound (HTlc) I. Removal of inorganic
      selenite (SeO3(2-)) from aqueous medium.
AB  - A Mg/Fe hydrotalcite-like-compound (HTlc) was prepared and its affinity toward
      the removal of SeO(3)(2-) from an aqueous medium was studied as a function of pH,
      time, temperature, particle dose, and SeO(3)(2-) concentration. The fraction of
      SeO(3)(2-) removal increases with decrease in both pH and temperature. The
      adsorption data are fitted to the Langmuir adsorption isotherm in the temperature
      range 303-333 K, and the thermodynamic parameters viz. standard Gibbs' free
      energy change (DeltaG degrees ), enthalpy change (DeltaH degrees ), and entropy
      change (DeltaS degrees ) are calculated. The negative value of DeltaH degrees
      indicates that the adsorption process is exothermic. The apparent equilibrium
      constants (K(a)) are also calculated and found to decrease with increase in
      temperature.

PMID- 16290699
TI  - Interaction of pyridine derivatives with sepiolite.
AB  - In this study, the adsorption behavior of pyridine derivatives, i.e., 2
      aminopyridine and 2,2'-bipyridyl, onto sepiolite, a natural clay mineral, has
      been investigated by bottle adsorption and IR spectroscopic techniques. The
      results indicate that 2-aminopyridine and 2,2'-bipyridyl molecules adsorb onto
      sepiolite through hydrogen bonding of the amino groups to the water molecules in
      the octahedral sheet and to the surface hydroxyls (Si-OH) in the tetrahedral
      sheet. These findings reveal that pyridine molecules not only adsorb onto the
      external surface of sepiolite but are also incorporated in its channels and
      tunnels with adsorption taking place at corners and/or edges, depending on the
      position of water molecules. A structural model is proposed to account for the
      orientation of pyridine derivatives in the sepiolite matrix.

PMID- 16290701
TI  - Galactosylated poly(N-isopropylacrylamide) hydrogel submicrometer particles for
      specific cellular uptake within hepatocytes.
AB  - Poly(N-isopropylacrylamide-co-acrylic acid) hydrogel submicrometer particles were
      prepared by free radical copolymerization of N-isopropylacrylamide and acrylic
      acid in the presence of a crosslinker above the lower critical solution
      temperature (LCST). They exhibited a reversible swelling and deswelling behavior:
      ca. 200-nm diameter below the LCST and ca. 100-nm diameter above the LCST. The
      hydrogel particles were tagged with fluorescent dye (FITC) in order to monitor
      the extent of cellular uptake and were further modified with galactose moieties
      to evaluate the extent of receptor-mediated endocytosis against HepG2 cells. Flow
      cytometry and confocal microscopy were used to investigate cellular uptake
      behaviors of the submicrometer particles. It was found that the extent of
      cellular uptake of submicrometer particles was far greater above the LCST than
      below the LCST, suggesting that smaller particles were taken up more readily
      within cells. When the submicrometer particles were galactosylated, the extent of
      cellular uptake increased dramatically due to receptor-mediated endocytosis. This
      study proposes a new possibility of controlling intracellular events such as
      protein and gene expression by a thermally modulated endocytosis process using
      thermo-sensitive microgel beads.

PMID- 16290700
TI  - Formation of protein-birnessite complex: XRD, FTIR, and AFM analysis.
AB  - Limited information is available on formation chemistry of enzyme-Mn oxide
      complexes. Adsorption isotherm of protein molecules (tyrosinase) on birnessite
      (delta-MnO(2)) at pH 6.0 and room temperature (23 degrees C) was of H type,
      indicating a very high affinity of the enzyme protein molecules to the birnessite
      mineral surfaces. After thorough washing of the protein-mineral complex with
      deionized-distilled water, up to 89% of adsorbed protein molecules remained bound
      to the mineral surfaces. When a high amount of the protein was immobilized, the X
      ray diffractogram shows a significant decrease in the intensity of characteristic
      d-spacings of birnessite. No shift to higher values of the d-spacings of protein
      birnessite complex was observed, indicating that the enzyme molecules were not
      intercalated in the mineral structure but immobilized at the external surfaces
      and the edges of the mineral oxide. By comparison to the free enzyme, infrared
      absorption spectra of the protein-birnessite complexes show a shift by up to 11
      cm(-1) to lower frequencies in the absorption bands characteristic of amide I and
      II modes of the polypeptides chains. The mineral surfaces exerted some strain on
      the protein structure, resulting in an alteration of the protein molecular
      conformation after binding to the mineral colloid surfaces. In the free state,
      the globular protein molecules had a spheroid shape with an average cross
      sectional diameter of 70+/-6 nm. The unfolding and flattening of the protein
      molecules after immobilization is clearly shown in atomic force micrographs.
      Compared to the tyrosinase-birnessite complex, similar FTIR spectra and atomic
      force micrographs were observed for the pure protein, bovine serum albumin (BSA),
      after immobilization on birnessite. The information obtained in this study is of
      fundamental significance for understanding birnessite as an adsorbent of
      biopolymers and the catalytic role of the enzyme-birnessite complex.

PMID- 16290702
TI  - Application of fluorescence correlation spectroscopy: a study of flocculation of
      rigid rod-like biopolymer (schizophyllan) and colloidal particles.
AB  - The flocculation between the rod-like biopolymer Schizophyllan and two types of
      colloidal particles (latex with diameter 40 nm and alumina with diameter 60 nm)
      has been investigated by means of fluorescence correlation spectroscopy (FCS).
      The concentration ratio of Schizophyllan/particle q was varied in the range 0.1
      approximately 20. Under conditions of pH about 5.7, 1 mmol.L(-1) NaCl, and room
      temperature (22+/-0.5 degrees C), the particles are strongly charged (alumina
      particles positively charged, latex negatively), while Schizophyllan is neutral.
      We observed that Schizophyllan chains flocculate with both types of particles,
      which suggests that the charge neutralization does not play a decisive role in
      these interactions. The ratio of fluorescence intensity of one floc over that of
      one particle, Q(f)/Q(p), and the corresponding hydrodynamic radius (r(h)) of the
      flocs have been measured. For a Schizophyllan-latex system, Q(f)/Q(p) reached a
      maximum value of 5 for q=3 indicating that the flocs contained five particles on
      average. The corresponding value of r(h) was r(h)=455 nm. The flocculation
      kinetic of latex particles with Schizophyllan was too fast to be measurable by
      FCS. For the Schizophyllan-alumina system, Q(f)/Q(p) was stable at about 1 in the
      whole studied range of q but r(h) increased with q suggesting that many
      Schizophyllan chains are adsorbed on individual particles. The flocculation
      kinetic of this system was studied by FCS and the obtained results were
      compatible with those of photon correlation spectroscopy.

PMID- 16290703
TI  - Dielectric behavior of some ferrofluids in low-frequency fields.
AB  - The dielectric behavior of a ferrofluid with magnetite particles dispersed in
      kerosene was analyzed taking into account the Schwarz model, concerning the low
      frequency dielectric behavior in systems consisting of colloidal particles
      suspended in electrolytes. For this reason, the complex dielectric permittivity
      and dielectric loss factor, in the frequency range of 10 Hz-500 kHz, at different
      temperatures between 20 degrees C and 100 degrees C were measured. Based on these
      experimental results, the experimental dependencies on both temperature of the
      relaxation time and activation energy of the relaxation process were analyzed.
      The obtained results show that the Schwarz model can be applied, in order to
      explain the low-frequency dielectric behavior of a ferrofluid with magnetite
      particles in kerosene, if the change of counterion concentration at the surface
      of colloidal particles is taken into account. Consequently, it is shown that the
      dielectric spectroscopy can be used in order to analyze the presence of particle
      agglomerations within ferrofluids.

PMID- 16290704
TI  - Emulsion polymerization synthesis of cationic polymer latex in an ultrasonic
      field.
AB  - Poly(methyl methacrylate) and poly(butyl acrylate) lattices have been synthesized
      under ultrasonic irradiation in the presence of a cationic surfactant,
      dodecyltrimethylammonium chloride. The polymerization of oil-in-water emulsions
      of monomeric species was carried out at 30 degrees C (+/-5 degrees C) in the
      absence of a chemical initiator. The lattices were formed as stable dispersions
      with particle diameters spanning the range of 40-150 nm and with polymer
      molecular weights greater than 10(6) g mol(-1). The results obtained strongly
      support a polymerization process involving a miniemulsion system, in which
      continuous nucleation of particles takes place throughout the monomer to polymer
      conversion reaction.

PMID- 16290705
TI  - Numerical solution of the poisson-boltzmann equation for a spherical cavity.
AB  - The Poisson-Boltzmann equation is numerically solved for a spherical cavity
      filled with a charged electrolyte solution. The network method used makes it
      possible to solve the problem in the most general case: the electrolyte solution
      can have any number of ion types with valences having any value. Furthermore, no
      a priori assumption concerning electroneutrality at the center of the cavity is
      required. Electric potential and ion concentration profiles, as well as the total
      potential drop in the cavity, are calculated for different system parameter
      values. These results are discussed and compared to the corresponding results
      obtained for suspended particles. Important differences arise, except for very
      thin double layers. For instance, the usual definition of the Debye length can no
      longer be used, since the electrolyte solution is nonneutral in the whole volume
      of the cavity. Furthermore, the charge density at the center of the cavity cannot
      be assigned any arbitrary value, since the charge density and the ion densities
      are no longer independent quantities.

PMID- 16290706
TI  - On packing constraints in the formation of surface micelles of amphiphiles at the
      metal/electrolyte interface-the necessity of introducing a generalized packing
      parameter.
AB  - The long-term capacity-time dependence of 1-decanol was measured at the
      mercury/electrolyte interface for the electrolytes KCl, NaCl, LiBr, and
      K(2)SO(4), each of concentration 0.1 M, in the temperature range 20 to 50 degrees
      C and at 35 degrees C for electrolyte concentrations of NaCl in the region 0.05
      to 0.4 M. All capacity-time dependences exhibited a slow increase of the capacity
      after a sudden decrease in the short-term range. The corresponding long-term time
      dependence of the degree of coverage can be theoretically well described with a
      first-order surface reaction. The ratios of final equilibrium capacity to minimal
      capacity can be explained with the formation of hemispherical or bilayer surface
      micelles from an initial monolayer of perpendicularly adsorbed molecules. A
      generalized packing parameter that involves the increase or decrease of the head
      groups' distance due to electrolyte ions or other surfactants was introduced. In
      the case of bilayers of parallel adsorbed molecules, obviously a new type of
      transition, which will be discussed in detail, occurs.

PMID- 16290707
TI  - Influence of aqueous electrolytes on the wetting behavior of hydrophobic solid
      polymers-low-rate dynamic liquid/fluid contact angle measurements using
      axisymmetric drop shape analysis.
AB  - The interaction of inorganic ions with low-energy hydrophobic surfaces was
      examined using model systems of solid polymers without ionizable functional
      surface groups in aqueous electrolyte solutions. Low-rate dynamic contact angle
      measurements with captive bubbles in conjunction with axisymmetric drop shape
      analysis (ADSA) were performed to study the influence of electrolyte ions (in the
      aqueous test solutions) on the wettability of the polymers. When various types of
      ions were used, no significant change in advancing and receding contact angles
      was observed. The contact angle hysteresis was small. The zeta potential of the
      model polymers in aqueous electrolyte solutions was determined from streaming
      potential measurements. The variation of the zeta potential at different pH
      levels indicates preferential adsorption of hydroxyl ions at this interface.
      However, the presence of electrolytes at the interface between water and the
      different model polymers did not influence the macroscopic contact angle. The
      results may suggest the absence of any specific interaction between the ions and
      the solid polymer, as this should result in changes of hydrophobicity. Similar to
      the air/water interface, the composition and the potential of the polymer/water
      interface are obviously determined predominantly by the aqueous phase with only
      slight influence from the solid phase.

PMID- 16290708
TI  - Sedimentation of concentrated spherical particles with a charge-regulated
      surface.
AB  - The sedimentation of a concentrated colloidal dispersion is examined for the case
      of an arbitrary double-layer thickness. Here, a general mixed-type condition on
      particle surface is assumed, and the classic models, which assume constant
      surface properties, can be recovered as the special cases of the present
      analysis. In particular, the behavior of biological cells, which carry
      dissociable functional groups on their surfaces, and particles, which are capable
      of exchanging ions with the surrounding medium, can be simulated by the present
      model. The mixed-type boundary condition leads to several interesting results in
      both sedimentation velocity and sedimentation potential as double-layer thickness
      and the concentration of particles vary.

PMID- 16290709
TI  - Investigation on solvent casting films of surfactant-encapsulated clusters.
AB  - The surfactant-encapsulated cluster (SEC) composed of a hydrophobic dimethyl
      dioctadecyl ammonium (DODA) shell and an encapsulated hydrophilic polyoxoanion
      core can form casting films. The structure of the casting film is influenced by
      evaporation rates of organic solvent. When the casting films are prepared by slow
      evaporation of chloroform, the alkyl chains are considered to possess a partial
      interdigitation, and the interdigitated length is 1.6 nm. The casting film
      structure is characterized by scanning force microscopy (SFM), Fourier
      transformation infrared (FT-IR), wide-angle X-ray diffraction, and differential
      scanning calorimetry (DSC).

PMID- 16290711
TI  - Application of the charge regulation model to transport of ions through
      hydrophilic membranes: one-dimensional transport model for narrow pores
      (nanofiltration).
AB  - The charge regulation concept is combined with the Navier-Stokes and Nernst
      Planck equations to describe the ion retention of nanofiltration membranes
      consisting of narrow cylindrical pores. The charge regulation approach replaces
      the assumption of a constant charge or a constant potential at the membrane pore
      surface, and accounts for the influence of pH, salt concentration, and type of
      electrolyte on ion retention. In the current model, radial concentration and
      potential gradients are considered to be negligibly small (valid for narrow
      enough pores), resulting in a one-dimensional transport description. The model
      describes typical experimental data for nanofiltration membranes, such as the
      change of ion retention with pore radius, ion concentration, pH, and pressure
      both for monovalent and multivalent ions. For a constant solvent velocity, the
      model in some cases predicts an optimum pore size for retention. Nonequal
      retentions for anions and cations are predicted at low and high pH values, as
      well as a minimum solvent velocity for very low salt concentrations. For higher
      salt concentrations, and at a fixed pressure difference, an increase in solvent
      velocity with increasing ion concentrations is predicted, in agreement with other
      one-dimensional transport descriptions found in the literature, but in contrast
      to some experimental data.

PMID- 16290710
TI  - Organization and properties of a conjugated poly(heteroarylene methines) at the
      air-water interface and in the Langmuir-Blodgett films.
AB  - A poly(heteroarylene methine) derivative, poly[(2,5-thiophenediyl) (p-n-methyl, n
      octylaminobenzylidene) (2,5-thiophenequinodimethaneiyl)] (PTABQ), has been
      synthesized and spread at the air-water interface. The influences of three kinds
      of solutions on PTABQ monolayer behavior at the air-water interface have been
      investigated via the measurements of the pi-A isotherm and film stability. The
      results show that all three kinds of PTABQ solutions are apt to form the stable
      and transferable monolayer film organized with the plane of its pi-system nearly
      perpendicular to the air-water interface. Moreover, the monolayer-forming ability
      of PTABQ can be improved by introducing a water-soluble amphiphilie as an
      extractable spread-aiding component, which is further proved by the AFM images
      and FTIR spectra of the transferred films. UV-visible absorption spectra indicate
      that the well-ordered layer-by-layer structure is successfully controlled in the
      LB films. The optical bandgap of PTABQ is reduced for the ordered arrangement of
      its molecules in LB films. The intrinsic electrical conductivity of PTABQ LB
      films is 8.1 x 10(-8) S/cm and the conductivity of iodine-doped films is 5.7 x
      10(-7) S/cm.

PMID- 16290712
TI  - Dissolution of the carbonate minerals of phosphate ores: catalysis by carbonic
      anhydrase II, from bovine erythrocytes, in acid solutions.
AB  - In this manuscript we report detailed experimental and theoretical evidence of
      the effect of carbonic anhydrase II, from bovine erythrocytes, on the dissolution
      process of carbonate minerals of phosphate ores (Epirus area, Greece) in dilute
      acetic acid, by recording the pH value of the acid solution as a function of time
      in the pH range from 2.37 to 6.40. We found that mass transfer makes a
      significant contribution to the determining step of the overall enzymatic
      reaction, while we distinguished five separate pH regions within the pH range
      from 2.37 to 6.40. Two different reaction systems and two model equations fitted
      perfectly the corresponding experimental data, and were used to evaluate all rate
      constants and parameters. Subsequently, we proposed the possible mechanisms of
      action for this enzyme from pH 2.37 to 6.40, within which carbonic anhydrase II
      was found active.

PMID- 16290713
TI  - Equilibrium adsorption of molybdosilicic acid solutions on carbon and silica:
      basic studies for the preparation of ecofriendly acidic catalysts.
AB  - Molybdosilicic acid solutions acidified with HCl were impregnated on carbon and
      silica by the equilibrium adsorption technique. From the equilibrium adsorption
      isotherms performed at 20 degrees C, it was established that the heteropolyacid
      amount adsorbed on carbon is higher than that on silica. Differences in shape and
      initial slope of the isotherm were observed. The interaction of the
      molybdosilicate anion was higher with carbon surface groups than with silanol
      groups. The physicochemical characterization of the solids has shown that the
      molybdosilicic acid presents an undegraded Keggin structure in the supported
      samples up to 250 degrees C. The surface acidity, mainly related to
      heteropolyacid adsorbed amount, was higher for samples on carbon. However, the
      silica-supported acid showed a bulk acidity higher than that on carbon, due to
      its lower interaction degree.

PMID- 16290714
TI  - Surface modification of montmorillonite on surface Acid-base characteristics of
      clay and thermal stability of epoxy/clay nanocomposites.
AB  - In this work, the effect of surface treatments on smectitic clay was investigated
      in surface energetics and thermal behaviors of epoxy/clay nanocomposites. The pH
      values, X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT
      IR) were used to analyze the effect of cation exchange on clay surface and the
      exfoliation phenomenon of clay interlayer. The surface energetics of clay and
      thermal properties of epoxy/clay nanocomposites were investigated in contact
      angles and thermogravimetric analysis (TGA), respectively. From the experimental
      results, the surface modification of clay by dodecylammonium chloride led to the
      increases in both distance between silicate layers of about 8 A and surface acid
      values, as well as in the electron acceptor component (gamma(+)(s)) of surface
      free energy, resulting in improved interfacial adhesion between basic (or
      electron donor) epoxy resins and acidic (electron acceptor) clay interlayers.
      Also, the thermal stability of nanocomposites was highly superior to pure epoxy
      resin due to the presence of the well-dispersed clay nanolayer, which has a
      barrier property in a composite system.

PMID- 16290715
TI  - Studies of synergism/antagonism for lowering dynamic interfacial tensions in
      surfactant/alkali/acidic oil systems, part 2: synergism/antagonism in binary
      surfactant mixtures.
AB  - Experimental studies are conducted in order to elucidate the mechanisms
      responsible for synergism/antagonism for lowering dynamic interfacial tension in
      hydrocarbons/binary surfactant mixtures/brine systems. The dynamic interfacial
      tensions between hydrocarbons of different alkane carbon numbers (from 6 to 14)
      and solutions of binary surfactant mixtures were measured. We found that the
      synergism/antagonism for interfacial tension reduction in binary surfactant
      mixtures having low interfacial tension values was influenced by the alkane
      carbon number of oil phase, hydrophilic-lipophilic ability of surfactant, and
      NaCl concentration. A new explanation in view of interactions among surfactant
      molecules, oil molecules, and water molecules is provided.

PMID- 16290716
TI  - Thermodynamic study of small hydrophobic ions at the water-lipid interface.
AB  - The thermodynamics of binding of two small hydrophobic ions such as norharman and
      tryptophan to neutral and negatively charged small unilamellar vesicles was
      investigated at pH 7.4 using fluorescence spectroscopy. Vesicles were formed at
      room temperature from dimyristoyl phosphatidylcholine (DMPC) or
      DMPC/dimyristoylphosphatidic acid and DMPC/dimyristoylphosphatidylglycerol. The
      changes in fluorescence properties were used to obtain association isotherms at
      variable membrane surface negative charge and at different ionic strengths. The
      binding of both ions was found to be quantitatively enhanced as the percentage of
      negative phospholipid increases in the membrane. Also, a decrease in ion binding
      was found to occur as the concentration of monovalent salt was increased (0.045
      0.345 M). If electrostatic effects were ignored, the experimental data showed
      biphasic behavior in Scatchard plots. When electrostatic effects were taken into
      account by means of the Gouy-Chapman theory, the same data yielded linear
      Scatchard plots that were described by a simple partition equilibrium of the
      hydrophobic ion into the lipid-water interface. We demonstrate that the effective
      interfacial charge, nu, of the ion is a determinant factor to obtain a unique
      value of the intrinsic (hydrophobic) binding constant independently of the
      surface charge density of the lipid membrane.

PMID- 16290717
TI  - Interfacial Behavior of n-decyl-beta-D-maltopyranoside on hydrophobic interfaces
      and the effect of small amounts of surface-active impurities.
AB  - The effect of small amounts of surface-active impurities on the interfacial
      properties of n-decyl-beta-D-maltopyranoside was investigated using various
      methods. The n-Decyl-beta-D-maltopyranoside was used both as received from Sigma
      (<98% by GC) and after being purified with the surfactant-purifying apparatus
      developed by Lunkenheimer, which removes impurities that are more surface active
      than the major component. Surface tension measurements demonstrate that the
      surface elasticity of the surfactant-loaded liquid-vapor interface increased
      after purification. Measurements of interactions across single foam films
      revealed that the purified solution formed considerably less charged and less
      stable films compared with the as-received sample. These results are consistent
      with the lower foam stability for the purified sample as determined by simple
      shaking experiments. The lower film stability for the purified solution was
      attributed to the lower double-layer force. The forces acting between spherical
      silanated glass surfaces across surfactant solutions were determined with the
      MASIF (measurement and analysis of surface interaction forces) technique. On
      approach, the same interactions were experienced in solutions of the as-received
      and purified surfactant. On the other hand, the adhesion force was lower after
      purification. Both for the as-received and the purified sample it was observed
      that the adhesion increased with increasing contact time up to a certain limit.
      This was explained in terms of partial pressure-induced desorption of surfactants
      from the disordered silane layers. Wetting experiments also indicated that the
      surfactants were difficult to remove completely from this surface.

PMID- 16290718
TI  - Viscosity of colloidal suspensions in aqueous gelatin.
AB  - The low-shear viscosity eta(0) of colloidal suspensions of acrylic latex or
      silica in aqueous gelatin has been measured at a temperature above the sol-gel
      transition. Measurements were made on dilution of a concentrated suspension with
      water or a gelatin solution. Thus, either the gelatin : colloid ratio was
      maintained or it was varied at constant aqueous gelatin concentration. Systems
      were studied with four lime-processed gelatins of different molecular weights at
      two concentrations of added salt. In addition, the latex particle size and the
      thickness of the adsorbed gelatin layer were measured by photon correlation
      spectroscopy (PCS) under dilute conditions. The dependence of the low-shear
      viscosity eta(0) on particle concentration was exponential and did not follow the
      well-established Krieger-Dougherty model for simple hard-sphere suspensions over
      the concentration range studied. A simple phenomenological model,
      eta(0)=eta(o)10(phi(e)/phi(s)), was found to predict the behavior well. Here,
      eta(o) is the viscosity of a gelatin solution of the corresponding solution
      concentration, phi(e) is proportional to the volume fraction of the particles,
      and phi(s) is a scaling factor, which was determined to have a value of 0.85.
      With this value of phi(s), the dimensions determined from PCS could be used to
      predict the viscosity values.

PMID- 16290719
TI  - Primary electroviscous effect in a suspension of charged porous spheres.
AB  - Primary electroviscous effect for a dilute suspension of porous spheres with
      fixed volumetric charge density is investigated theoretically. In the absence of
      flow, the electrical potential and solution charge density are assumed to satisfy
      the linearized Poisson-Boltzmann equation. With incorporation of the electrical
      body force, the Brinkman equation and the Stokes equation are used to govern the
      fluid flow inside and outside a sphere. The theory is formulated by assuming weak
      deviation of the charge cloud from its equilibrium state. However, the electrical
      body force is not restricted to be small compared to the viscous force in the
      fluid momentum equation. The results show that the double layer distortion is
      increased with increasing particle permeability, thereby enhancing the relative
      importance of its stress contribution. Nonetheless, the intrinsic viscosity
      remains a decreasing function of permeability, similar to the case of uncharged
      particles.

PMID- 16290720
TI  - Electrophoretic mobility of rigid rodlike particles in dilute aqueous and
      glycerol suspensions: comparison between theory and experiment.
AB  - The electrophoretic mobilities of rigid rodlike tobacco mosaic virus (TMV)
      particles solvated in water and in 80% glycerol/20% water solutions with a wide
      range of electrical double-layer thicknesses have been measured by Deggelmann et
      al. (Deggelmann, M., Graf, C., Hagenbuchle, M., Hoss, U., Johner, C., Kramer, H.,
      Martin, C., and Weber, R., J. Phys. Chem.98, 364-368 (1994)) and the present
      authors, respectively. The measured mobilities have a dependence on the
      electrical double-layer thickness much weaker than that predicted by theories for
      the mobility of cylinders of infinite length. To interpret the experiments, we
      develop an approximate theory for the mobility of finite aspect ratio particles
      with arbitrary ratios of the double-layer thickness to the rod length and
      diameter. This uniformly valid approximation interpolates between previous
      theories for infinite rod length and for infinitesimal rod thickness. A
      comparison of the uniformly valid theory with the experimentally measured
      mobilities indicates that TMV has a negative charge of 1000e in water and 400e in
      the glycerol solution.

PMID- 16290721
TI  - Plasma polymerization of aniline on different surface functionalized substrates.
AB  - The plasma polymerization of aniline on different surface functionlized low
      density polyethylene (LDPE) substrates was investigated, and the resulting
      polymer was characterized by X-ray photoelectron spectroscopy, Fourier transform
      infrared spectroscopy, scanning electron microscopy, and atomic force microscopy.
      The results showed that the structure of plasma-polymerized polyaniline was
      rather different from polyaniline synthesized by conventional chemical and
      electrochemical methods. This difference may be due to extensive coupling
      reactions and cross-linking reactions during the plasma polymerization process.
      The use of acrylic acid graft copolymerized LDPE substrate significantly enhanced
      the adhesion of the polyaniline to the substrate over that observed with pristine
      LDPE. The plasma polymerized polyaniline can be rendered electrically conductive
      if the polymerization is carried out on a polystyrenesulfonic acid-coated LDPE
      substrate. Conductivity can also be induced by acid protonation of the
      polyaniline by HClO(4). The reaction of the plasma-polymerized polyaniline with
      viologen grafted on the substrate under UV irradiation and with AuCl(3) and
      Pd(NO(3))(2) in acid solutions was also investigated.

PMID- 16290722
TI  - Effect of acidic surface treatment of red mud on mechanical interfacial
      properties of epoxy/red mud nanocomposites.
AB  - In this work, red mud (RM) was chemically modified by 0.1, 1, and 5 M H(3)PO(4)
      solution to prepare epoxy/RM nanocomposites. The effect of chemical treatment on
      a RM surface was studied in terms of pH, acid-base values, N(2)/77 K gas
      adsorption, equilibrium spreading pressure (pi(e)), and surface free energy. The
      mechanical interfacial properties of epoxy/RM nanocomposites was measured in the
      context of critical stress intensity factor (K(IC)) and critical strain energy
      release rate (G(IC)) measurements. From the experimental results, the acidic
      surface treatment led to a modification of the RM surface properties, such as the
      surface acid values, porosity, specific surface area, pi(e), and London
      dispersive component (gamma(S)(L)) of surface free energy of the treated RM as an
      increase of the treatment concentration. In the fracture toughness (K(IC) and
      G(IC)) measurements, the mechanical interfacial properties of epoxy/treated RM
      nanocomposites were intimately correlated with the improvement of interfacial
      adhesion between the RM surface and a matrix and the increase of gamma(S)(L) of
      surface free energy of the RM due to the development of S(BET) or porosity of RM
      surfaces.

PMID- 16290723
TI  - Novel method for linking CdS nanoparticles at liquid-liquid interface.
AB  - Liquid-liquid interface of water-hexane provides a unique reaction environment in
      which CdS nanoparticles capped with mercaptoethylamine could be linked together
      to form a homodimer with a divalent acid chloride, sebacoyl chloride. Prior to
      the reaction, mercaptoethylamine-capped CdS in aqueous solution was purified by
      dialysis and freeze-drying. The observation with a transmission electron
      microscope suggested the formation of a homodimer of CdS nanoparticles.

PMID- 16290725
TI  - Adsorption characteristics and the kinetics of the cation exchange of rhodamine
      6G with Na+-montmorillonite.
AB  - The adsorption and the kinetics of the cation exchange of rhodamine-6G (Rh-6G)
      with Na(+)-montmorillonite (Na(+)-MMT) have been studied. The binding parameters
      of Rh-6G have been determined by applying Freundlich and D-R isotherms. The
      enthalpy and the entropy of adsorption have been determined. The isosteric heat
      of adsorption has also been determined and decreases with increasing the
      concentration of Rh-6G. Increasing the concentration of Rh-6G led to a decrease
      in the adsorption capacity, which attributed to the formation of Rh-6G
      aggregates. Kinetic measurements of the cation exchange were followed up using a
      stopped-flow electrical conductivity detection unit. The cation-exchange process
      exhibited first-order kinetics with respect to the dye concentration and
      inversely proportional to the clay concentration. The measurements were
      accomplished at different temperatures and the activation parameters were
      determined. Increasing the Na(+)-MMT concentration led to a decrease in the rate
      constant. The latter is also affected by changing the exchangeable cation.

PMID- 16290726
TI  - Microporous activated carbons prepared from palm shell by thermal activation and
      their application to sulfur dioxide adsorption.
AB  - Textural characterization of activated carbons prepared from palm shell by
      thermal activation with carbon dioxide (CO(2)) gas is reported in this paper.
      Palm shell (endocarp) is an abundant agricultural solid waste from palm-oil
      processing mills in many tropical countries such as Malaysia, Indonesia, and
      Thailand. The effects of activation temperature on the textural properties of the
      palm-shell activated carbons, namely specific surface area (BET method),
      porosity, and microporosity, were investigated. The activated carbons prepared
      from palm shell possessed well-developed porosity, predominantly microporosity,
      leading to potential applications in gas-phase adsorption for air pollution
      control. Static and dynamic adsorption tests for sulfur dioxide (SO(2)), a common
      gaseous pollutant, were carried out in a thermogravimetric analyzer and a packed
      column configuration respectively. The effects of adsorption temperature,
      adsorbate inlet concentration, and adsorbate superficial velocity on the
      adsorptive performance of the prepared activated carbons were studied. The palm
      shell activated carbon was found to have substantial capability for the
      adsorption of SO(2), comparable to those of some commercial products and an
      adsorbent derived from another biomass.

PMID- 16290727
TI  - Investigation of removal of Cr(VI), Mo(VI), W(VI), V(IV), and V(V) oxy-ions from
      industrial waste-waters by adsorption and electrosorption at high-area carbon
      cloth.
AB  - Adsorption and electrosorption of Cr(VI), Mo(VI), W(VI), V(IV), and V(V) ions
      from water samples at low concentration were studied at high-area C-cloth
      electrodes. The concentrations of ions in the solution were monitored using in
      situ UV spectroscopy. All the investigated ions, except V(IV), showed better
      adsorption in acidic media. Positive polarization of the C-cloth caused increased
      adsorption of Cr(VI), Mo(VI), and V(V) ions. When previously adsorbed, Mo(VI) and
      V(V) ions were shown to be largely desorbable by negative polarization of the C
      cloth. Since V(IV) does not become adsorbed significantly at the C-cloth in
      acidic media, the method provides an interesting means for separation of V(V) and
      V(IV) species in solution.

PMID- 16290728
TI  - Study on osmotic pressures for aqueous lysozyme and alpha-chymotrypsin
      electrolyte solutions with two Yukawa potentials.
AB  - The equation of state (EOS) of Duh and Mier-y-Teran for one Yukawa potential is
      expanded to two Yukawa potentials to describe the nonidealities of the charged
      lysozyme and alpha-chymotrypsin solutions. Instead of the classical DLVO theory,
      the attractive dispersion and double-layer repulsion interactions are represented
      by two Yukawa potentials, respectively. For the aqueous lysozyme solutions, the
      only adjustable dispersion energy parameter epsilon/k is regressed and the
      average deviation is 1.76%. For the aqueous alpha-chymotrypsin solutions, two
      adjustable parameters (the molecular weight and dispersion energy parameter) are
      regressed and the average deviation is 7.62%. Some correlation and prediction
      results are discussed.

PMID- 16290729
TI  - Influence of soft drinks on the thickness and morphology of in situ acquired
      pellicle layer on enamel.
AB  - Diet-induced demineralization is a key factor in tooth enamel loss, with soft
      drinks being a significant aetiological agent. In the oral environment, the
      acquired pellicle layer might modify the demineralization potential of drinks.
      The objectives of this exploratory in situ study were to determine the influence
      of soft drinks, volunteers, and exposure times on the thickness and morphology of
      pellicle layers using an atomic force microscope (AFM). Polished uninterrupted
      third molars were partly taped and exposed to the oral environment for periods of
      2 and 5 days, respectively. Each day 1L of either mineral water, a "toothkind"
      blackcurrant drink, a "prototype" blackcurrant drink, or orange juice was
      consumed in this four-way crossover, single-center study. Subsequently the tape
      was removed and the surfaces imaged with an AFM before and after chemical
      cleaning. The pellicle layer morphology and thickness were investigated. The
      maximum pellicle layer thickness was observed after the consumption of the
      prototype blackcurrant drink, followed by the toothkind blackcurrant drink,
      orange juice, and water on days 2 and 5, respectively. A three-way ANOVA at the
      95% confidence level showed statistically significant differences between the
      pellicle layer thicknesses, factors being drinks (p=0.0046), exposure time
      (p=0.0009), and volunteers (p=0.0244). Depending on the volunteer either a
      uniform or a patchy pellicle layer was observed. This demonstrates that AFM is a
      useful tool in obtaining simultaneously qualitative and quantitative data of in
      situ acquired pellicle layers.

PMID- 16290730
TI  - Effect of amphiphilic drugs on the stability and zeta-potential of their liposome
      formulations: a study with prednisolone, diazepam, and griseofulvin.
AB  - Multilamellar liposomes consisting of phosphatidylcholine and incorporating
      prednisolone (PZ), diazepam (DZ), or griseofulvin (GF) were prepared and
      characterized. Liposome size, surface charge, and stability (in buffer and serum
      proteins) were measured for drug-incorporating liposomes and empty liposomes for
      comparison. The results reveal that for all drugs studied drug incorporation has
      a substantial effect on the vesicle zeta-potential and stability. Drug
      incorporating liposomes have a negative surface charge, while their membrane
      integrity is significantly higher when compared with that of empty liposomes.
      Release of DZ from liposomes is induced by dilution. Summarizing, the results of
      this study demonstrate that the presence of PZ, DZ, or GF in liposome membranes
      has a significant effect on main vesicle properties and correlates well with
      those obtained previously for hydrochlorothiazide and chlorothiazide. Thereby, we
      may conclude that the previously demonstrated effects of the thiazides on
      liposome properties are not solely related to their structure.

PMID- 16290731
TI  - Study of two grafting methods for obtaining a 3-aminopropyltriethoxysilane
      monolayer on silica surface.
AB  - In order to establish a 3-aminopropyltriethoxysilane (APTES) grafting procedure
      with limited number of APTESs noncovalently linked to the silica surface, two
      different methods of grafting (in acid-aqueous solution and in anhydrous
      solution) were compared. The grafted surface state was investigated by atomic
      force microscopy (AFM). The stability of the grafting was checked at different
      temperatures by AFM. Continuous and plane APTES grafted surfaces were
      successfully prepared using both grafting preparations. The grafting in an
      anhydrous solution behaves homogeneously and stably compared to the grafting in
      an acid-aqueous solution. Moreover, with anhydrous solution, results showed that
      a unique monolayer of APTES was grafted.

PMID- 16290732
TI  - Preparation of nanosized drug particles by the coating of inorganic cores:
      naproxen and ketoprofen on alumina.
AB  - Nanosized alumina particles with modal diameters of 8 and 13 nm, respectively,
      were successfully coated by the adsorption of naproxen [(+)-6-methoxy-alpha
      methyl-2-naphthalene acetic acid] and ketoprofen [alpha-methyl-3-(4
      methylbenzoil) benzene acetic acid] in aqueous and ethanol solutions. The
      presence of the drugs at the alumina surface was confirmed by attenuated total
      reflection infrared spectroscopy and electrokinetic measurements, while their
      bound amounts were assessed by thermogravimetric analysis.

PMID- 16290733
TI  - Morphological analysis of the effects of ions and ultraviolet light on colloidal
      monolayers at the air-water interface.
AB  - The formation of fractal aggregates under the external influence of ions or
      ultraviolet light has been observed in colloidal monolayers trapped at the air
      water interface. A morphological analysis of this is reported in this paper.
      These fractals have many characteristics similar to those observed in other
      experiments where electrolyte was added to the bulk. However, they exhibit
      behavior, such as restructuring, particular to the external influence. In most
      cases the aggregating system displayed scaling analogous to spinodal
      decomposition, but with the measured fractal dimension (which depends slightly on
      the external influence) entering in place of the usual spatial dimension.

PMID- 16290734
TI  - On the influence of size, zeta potential, and state of motion of dispersed
      particles on the conductivity of a colloidal suspension.
AB  - The dependence of the DC conductivity of diluted colloidal suspensions on the
      size, zeta potential, and state of motion of the dispersed particles is analyzed
      both theoretically and numerically. It is shown that the simple formula that
      represents the conductivity as a sum of products: charge times mobility, taken
      over all the carriers present in the suspension, is only valid for exceedingly
      low values of the product kappaa. In contrast, the formulation based on the value
      of the dipolar coefficient of the suspended particles seems to be valid for all
      the range of particle sizes. This assertion is only true if the dipolar
      coefficient is calculated taking into account the electrophoretic motion of the
      particles. For very low values of the product kappaa, the dipolar coefficient of
      particles free to move can be several orders of magnitude larger than that of
      immobile particles.

PMID- 16290736
TI  - Electrophoretic motion of a slightly deformed sphere with a nonuniform zeta
      potential distribution.
AB  - Electrophoretic motion is analyzed for a rigid, slightly deformed sphere with a
      nonuniform zeta potential distribution. Hydrodynamics and electrostatics
      solutions for the deformed sphere with an arbitrary double-layer thickness are
      determined by using the domain perturbation method. The surface shape and the
      zeta potential distribution for the deformed sphere are expressed by using the
      multipole expansion representation. In terms of monopole, dipole, and quadrupole
      moments of the surface shape and the zeta potential distribution, explicit
      expressions are obtained for the translational and rotational electrophoretic
      mobility tensors. The ensemble average for the mobility of the deformed sphere
      with a uniform orientation distribution is also derived. The utility of the
      general mobility expression is demonstrated by studying the electrophoretic
      motion of axisymmetric and ellipsoidal particles. The translational and
      rotational mobilities of axisymmetric particles are both affected by the
      monopole, dipole, and quadrupole moments of the zeta potential. For ellipsoidal
      particles, however, the dipole moment of the zeta potential does not affect the
      translational mobility, while the rotational mobility depends only on the dipole
      moment. The mobility of the deformed sphere with either a thick or a thin double
      layer is also derived.

PMID- 16290735
TI  - Direct measurement of concentration distribution within the boundary layer of an
      ion-exchange membrane.
AB  - In this study the concentration distributions within the diffusion boundary layer
      were obtained by directly measuring the potential drops while the currents (under
      and overlimiting) passed through the Neosepta CMX cation-exchange membrane
      (Tokuyama Corp., Japan). Potential drops according to the distance from the
      membrane surface on the depleted side were measured using a microelectrode to
      obtain the concentration profile. From the concentration profiles obtained, it
      was observed that the diffusion boundary layers existed in the range of 300-350
      microm, which reasonably coincide with the theoretical diffusion boundary layer
      thickness calculated from the limiting current density. Although there were some
      deviations between the concentrations determined from the Nernst model and those
      from experiments, it was confirmed that the Nernst model effectively depicts the
      transport phenomena in the ion-exchange membrane system. In addition it was found
      that the salt concentration at the membrane surface increased when the currents
      applied exceeded the limiting current. It is thought that the concentration
      polarization formed in the diffusion boundary layer at currents near or lower
      than the limiting current was disturbed by a turbulent convection when the
      current was greater than the limiting current. As a consequence, the
      concentration at the membrane surface increased to a sufficient level for
      generation of the overlimiting current.

PMID- 16290737
TI  - Electrophoretic motion of a sphere in a microchannel under the gravitational
      field.
AB  - This paper considered electrophoretic motion of a sphere in an aqueous
      electrolyte solution in a microchannel under the gravitational field. In an
      externally applied electric field, the negatively charged sphere will move toward
      the anode. At the same time, the sphere will move toward the lower channel wall
      due to the density difference and the gravity. When the sphere moves very close
      to the lower wall, the buoyancy, the electric double layer interaction force, and
      the van der Waals force balance the gravity force, so the sphere moves parallel
      to the lower wall. A theoretical model for the electrophoretic motion of a sphere
      in a microchannel, with the consideration of the electrophoretic retardation
      effect, is presented in this paper. It was found that the sphere's motion in the
      microchannel is affected by its size, the density difference, the zeta potentials
      of the sphere and the channel wall, and the applied electric strength. The
      effects of these factors on the sphere's transport distance in the microchannel
      are discussed. It was found that the spheres with the same surface charge could
      be separated by their size within a certain range of ka in aqueous solutions in
      the microchannel.

PMID- 16290738
TI  - Group contribution method for the estimation of contact angle trends on modified
      polymer surfaces.
AB  - Group contribution methods can be used as an aid in evaluating contact angle data
      on modified polymer surfaces. Good correlation was seen between experimental
      contact angle titration data on a hydrolyzed polyimide surface and equations
      involving water-octanol partition coefficients using parameters derived from
      group contribution methods. The methods used captured features of the
      experimental contact angle titration data observed during ionization of surface
      functional groups.

PMID- 16290739
TI  - Strong adhesion and smooth conductive surface via graft polymerization of aniline
      on a modified glass fiber surface.
AB  - The goal of this paper is to prepare surface-conductive glass fibers. The fibers
      were first hydroxylated, after which they were reacted with 3
      bromopropyltrichlorosilane to form a bromopropylsilane monolayer, which was
      further reacted with aniline to substitute the bromine atoms. The surface-bound
      aniline molecules were used as active sites for the graft polymerization of
      polyaniline (PANI). The composition, structure and the morphology of the modified
      glass fiber surface were examined by X-ray photoelectron spectroscopy, scanning
      electron microscopy, and Fourier transform infrared spectroscopy. The method
      generated a smooth and homogenous thin layer of PANI on the surface of the glass
      fiber with a surface conductivity of about 6 S/cm, hence larger than the usual
      value ( approximately 1 S/cm) of the bulk polyaniline.

PMID- 16290740
TI  - Complexity of intercalation of hydrazine into kaolinite--a controlled rate
      thermal analysis and DRIFT spectroscopic study.
AB  - Controlled rate thermal analysis (CRTA) allows the separation of adsorbed and
      intercalated hydrazine. CRTA displays the presence of three different types of
      hydrogen-bonded hydrazine in the intercalation complex: (a) The first is adsorbed
      loosely bonded on the kaolinite structure fully expanded by hydrazine-hydrate and
      liberated between approx 50 and 70 degrees C (b) The second intercalated
      hydrazine is lost between approx 70 and 85 degrees C. (c) The third type of
      intercalated-hydrazine molecule is lost in the 85-130 degrees C range. CRTA at 70
      degrees C enables the removal of hydrazine-water and results in the partial
      collapse of the hydrazine-intercalated kaolinite structure to form a hydrazine
      intercalated kaolinite. Removal of the adsorbed hydrazine enables the DRIFT
      spectra of the hydrazine-intercalated complex without any adsorbed hydrazine to
      be obtained. A band at 3626 cm(-1) attributed to the inner surface hydroxyls of
      kaolinite hydrogen bonded to hydrazine is observed. The intercalation of
      hydrazine-hydrate into kaolinite is complex and results from the different types
      of surface interactions of the hydrazine with the kaolinite surfaces.

PMID- 16290741
TI  - Release studies on niosomes containing fatty alcohols as bilayer stabilizers
      instead of cholesterol.
AB  - Monomers of some amphiphiles organize into bilayers to form liposomes and
      niosomes. Such bilayers are unstable or leaky and hence cholesterol is a common
      ingredient included to stabilize them. Cholesterol stabilizes bilayers, prevents
      leakiness, and retards permeation of solutes enclosed in the aqueous core of
      these vesicles. Other than cholesterol a material with good bilayer-stabilizing
      properties is yet to be identified. We have substituted cholesterol with fatty
      alcohols in niosomes containing polyglyceryl-3-di-isostearate (PGDS) and
      polysorbate-80 (PS-80) to explore their membrane-stabilizing property via
      permeation studies. Niosomes of polyglyceryl-3-di-isostearate, fatty
      alcohol/cholesterol, and polysorbate were prepared by ether injection method.
      Aqueous solution of ketorolac tromethamine (KT) was entrapped in them. The
      effects of alkyl chain length of fatty alcohols (C(12), C(14), C(16), C(18), and
      C(16+18)), of acyl chain length of polyoxyethylene sorbitan monoester
      surfactants, and of the molar ratio of lipid mixture on the release rate of
      ketorolac from niosomes were assessed by employing modified dissolution-dialysis
      method. Niosomes with cholesterol or fatty alcohols have exhibited a common
      release pattern. Niosomes containing fatty alcohol showed a considerably slower
      release rate of KT than those containing cholesterol. Based on the release rate,
      fatty alcohols can be ranked as stearyl<myristyl<cetyl<lauryl<cetostearyl. In
      niosomes containing PGDS, myristyl alcohol (MA), and polysorbate, the fatty acid
      chain length of polyoxyethylene sorbitan ester-type surfactants has influenced
      the release rate and encapsulation efficiency. Based on the release rate,
      polysorbates can be ranked as polysorbate-20 (C(12))<polysorbate-60
      (C(18))<polysorbate-80 (C(9=9))<polysorbate-40 (C(16)). In niosome preparation
      containing polysorbate-20 and dioctyl sodium sulfosuccinate (anionic surfactant),
      the release rate was slower than niosomes containing polysorbate-20. When MA
      concentration is kept constant at 50 mole% and the ratio of PGDS and PS-80 was
      altered, significant changes in entrapment efficiency and the release rate were
      observed. However, this ratio did not exhibit any relation with encapsulation
      efficiency or release rate. The release rate and entrapment exhibited an inverse
      correlation (r(2)=0.8774 at p<0.02 for the data of molar ratios of PGDS:MA:PS80;
      r(2)=0.975 at p<0.001 for the data of acyl chain length variation of
      polysorbates). It can be concluded that stable niosomes of polyglyceryl-3-di
      isostearate could be prepared with fatty alcohols and polysorbates instead of
      cholesterol and that the release of solutes from these niosomes can be optimized
      by altering membrane constituents and their concentrations.

PMID- 16290742
TI  - Micellar solubilization: structural and conformational changes investigated by 1H
      and 13C liquid-state NMR.
AB  - A combination of (1)H self-diffusion measurements and (13)C chemical shift
      analysis has been used for the study of the solubilization of amphiphilic
      additives C(n)H(2n+1)X (n=4, 6; X=OH, NH(2)) in cetyltrimethylammonium bromide
      (CTAB) micelles. This approach, which could be extended to other mixed systems,
      allows complementary data on structures of micelles and conformations of alkyl
      chains to be obtained. Previous results on these systems are confirmed and new
      features emerge. All the additives studied behave as cosurfactants. Their degree
      of solubilization is determined solely by their alkyl chain length. In the case
      of cosurfactants with n=6, polar head group differences have been shown to modify
      micellar structures. This effect has been linked to differences in cosurfactant
      penetration into micelles. In parallel, the area of CTAB head groups and the
      length of cetyl chains gradually decrease on average when solubilizing more
      cosurfactants. Cetyl chain compression is strong in the case of cosurfactants
      with n=4, whereas it is slightly compensated by an extension below the micellar
      surface in the case of longer cosurfactants. These conformational changes are
      related respectively to the formation of smaller spherical micelles and of
      anisotropic or swollen micelles.

PMID- 16290743
TI  - In situ sol-gel preparation of polysaccharide/titanium oxide hybrid colloids and
      their electrorheological effect.
AB  - A new type of organic/inorganic hybrid colloid, made of modified carboxylmethyl
      starch (CMS) and titanium oxide (TiO(2)), was synthesized by an in situ sol-gel
      technique. IR spectra analysis shows strong a interaction of functional groups
      between two components, whose dispersion is almost at the molecular level. Due to
      the highly active surfaces hybrid particles and their characteristic dielectric
      behavior in accordance with the previous theoretic calculation, the suspensions
      of hybrids in silicone oil display a remarkable ER effect. The static yield
      stress can be above 20 kPa (shear rate 5 S(-1)) under a direct current field of 4
      kV/mm at room temperature, much higher than that of simple blends of starch and
      titanium dioxide. In the meanwhile, the temperature dependence and sedimentation
      stability were optimized. Based on existing experimental results, we propose that
      dielectric properties and surface (interface) activity are two necessary
      conditions fulfilling the requirement of high ER activity. The combination of
      both factors may effectively reduce the activation energy needed for ERF
      restructuring.

PMID- 16290744
TI  - Impact of self-assembled surfactant structures on rheology of concentrated
      nanoparticle dispersions.
AB  - Rheological behavior of surfactant-stabilized colloidal dispersions of silica
      particles under extreme conditions (low pH, high ionic strength) has been
      investigated in relation to interparticle forces and stability of the dispersion.
      The surfactant used as the dispersing agent was C(12)TAB, a cationic surfactant.
      Stability analysis through turbidity measurements indicated that there is a sharp
      increase in the stability of the dispersion when the surfactant concentration is
      in the range of 8 to 10 mM in the system. The state of the dispersion changes
      from an unstable regime to a stable regime above a critical concentration of
      C(12)TAB in the system. In the case of interaction forces measured between the
      silica substrate and AFM tip, no repulsive force was observed up to a surfactant
      concentration of 8 mM and a transition from no repulsive forces to steric
      repulsive forces occurred between 8 and 10 mM. Rheological measurements as a
      function of C(12)TAB concentration indicated a significant decrease in the
      viscosity and linear viscoelastic functions of the dispersion over the same range
      of surfactant concentration (8 to 10 mM C(12)TAB), showing a strong correlation
      between the viscosity behavior, interparticle forces, and structure development
      in the dispersion.

PMID- 16290745
TI  - Elongational flow of solutions of poly(ethylene oxide) and sulfonated
      surfactants.
AB  - In this work, the elongational flow behavior of aqueous solutions of
      poly(ethylene oxide) (PEO) was studied in the presence of sulfonated surfactants.
      The technique of opposed-jets flow was used to generate an elongational flow
      field in which pressure drops were measured as a function of strain rates. The
      surfactants used were sodium dodecyl benzene sulfonate (SDBS) and an alpha-olefin
      sulfonate (AOS). Solutions of PEO and other flexible polymers exhibit extension
      thickening in opposed-jets flow due to the formation of transient networks of
      entangled molecules. This effect is present at concentrations below the static
      coil overlap concentration, due to the changes in molecular conformation induced
      by the flow. When SDBS or AOS are added to PEO solutions at low concentrations,
      the extension thickening weakens due to an increase in PEO intramolecular
      interactions that lead to coil contraction. This occurs until the surfactant
      concentration is close to the critical aggregation concentration reported in the
      literature. Further addition of surfactant induces the formation of
      intermolecular interactions as the PEO molecules are expanded by the
      electrostatic repulsion between attached micellar aggregates, with an associated
      strengthening of extension thickening. Intramolecular effects were not seen
      beyond a specific PEO concentration.

PMID- 16290746
TI  - Structure and properties of hydrophobically end-capped poly(ethylene oxide)
      solutions in the presence of monovalent and divalent cations.
AB  - Hydrophobically modified poly(ethylene oxide), HMPEO, was studied in concentrated
      salt solutions. The influence of salts was compared to the effect of temperature
      on poly(ethylene oxide), PEO. As expected, the addition of monovalent cations
      (Na(+), K(+)) has the same effect as an increase in temperature in agreement with
      the thermodynamic properties of PEO: a decrease in solubility, micelle size, and
      viscosity was observed. Moreover, the intensity of neutron scattering peaks
      (characteristic of the semi-dilute solutions of these associative polymers)
      increases due to the collapse of PEO coronae in micelles. Very peculiar behavior
      was observed in the presence of divalent cations (Ca(2+), Mg(2+)): larger micelle
      aggregates and higher viscosities, relaxation times, and activation energies were
      observed by dynamic rheology. This behavior is attributed to interactions between
      divalent cations and oxygen in PEO backbones close to the micelle core, which may
      reinforce intermicellar bridges.

PMID- 16290747
TI  - Swelling of interpenetrating networklike particles in a soft polymer matrix.
AB  - Fast transient fluorescence technique was used to monitor swelling of hard latex
      particles in a soft polymer matrix. Various film samples were prepared from
      pyrene (P) and/or naphthalene (N)-labeled poly(methyl methacrylate) (PMMA)
      particles in a low-molecular-weight poly(isobutylene) (PIB) matrix. These PMMA
      particles contain interpenetrating PIB channels. Film samples were annealed at
      elevated temperatures to promote particle swelling. Fluorescence lifetimes, tau,
      were measured for each film sample. It was observed that tau values decrease as
      the PIB content in the matrix is increased. The decrease in tau was explained by
      the increase in quenching of excited P and N molecules by low-molecular-weight
      PIB penetrating into the PIB channels in the PMMA particles. A drastic decrease
      in tau above a certain temperature was attributed to the effect of particle size
      on the swelling of the latex particles in the PIB matrix. It was observed that
      small particles (P-labeled) swell at much lower annealing temperatures than large
      (N-labeled) particles.

PMID- 16290748
TI  - Melt, hydration, and micellization of the PEO-PPO-PEO block copolymer studied by
      FTIR spectroscopy.
AB  - Fourier transform infrared (FTIR) spectroscopy was used to study the
      conformational changes of the polyethylene oxide-polypropylene oxide-polyethylene
      oxide (PEO-PPO-PEO) block copolymer, Pluronic P104, in a large concentration
      range in a polymer-water system as a function of temperature. The melt in which
      the conformational transition of the PEO blocks occurs gives remarkable changes
      in the spectral behavior. A small amount of water in Pluronic P104 can induce the
      PEO block amorphism. The addition of more water only swells the PEO dominant
      region and gives no significant difference in the conformational structure of the
      block copolymer in the ordered phases of Pluronic P104-water mixtures. The PPO
      blocks of Pluronic P104 are hydrated only in a condition of lower temperature and
      higher water content. The temperature dependent micellization of Pluronic P104 in
      water was analyzed by a FTIR spectroscopic method. The appearance of the
      symmetric deformation band of the anhydrous methyl groups at temperature below
      the CMT indicates the existence of a hydrophobic microenvironment. The appearance
      of the symmetric deformation band of the hydrated methyl groups at higher
      temperatures indicates that the micellar core must contain some amount of water.
      The results of FTIR data show that the proportion of the anhydrous methyl groups
      increases and water content in the micellar core decreases during the
      micellization process.

PMID- 16290749
TI  - Observation of phase transition of thermo-responsive poly(NIPA)-PEI block
      copolymers by STM.
AB  - N-isopropylacrylamide (NIPA) homopolymers having carboxylic acid-end groups were
      synthesized by using mercaptoacetic acid (MAA) as the chain transfer agent.
      Polymerization was achieved in ethanol using azobisisobutyronitrile (AIBN) as the
      initiator. Average molecular weight of the homopolymer estimated by titration was
      1958. This carboxylic acid-ended poly(NIPA) was then copolymerized with
      polyethylenimine (PEI, M(W)-2000) using a water soluble carbodiimide (EDAC). With
      respect to carboxyl-ended poly(NIPA), the block copolymers exhibited a pH
      dependent-temperature sensitivity and higher LCST values in acidic pH. Scanning
      tunneling microscopy (STM) images of both the homopolymer and the copolymer were
      obtained at 25 and 45 degrees C with tip-sample bias voltages of up to 800 mV and
      tunneling currents approximately 1 nA. These images showed that STM can be used
      to visualize both the formation of copolymer chains and their structure, and also
      their stimuli-responsive behavior.

PMID- 16290750
TI  - Reflection and polarization of light by semi-infinite turbid media: simple
      approximations.
AB  - The paper is devoted to the investigation of the accuracy of the Rozenberg
      approximation for the reflection function of a semi-infinite absorbing random
      media. We found that this approximation can be used at y<0.5, where y= square
      root (1-omega (0))/(3(1-g)) . Here omega(0) is the single scattering albedo and g
      is the asymmetry parameter. We also propose the modified approximation, which can
      be used at least up to y=1-2, depending on the observation geometry.

PMID- 16290751
TI  - Assessment of small-angle and angle-averaged structure factor for monitoring
      electrostatic colloidal interactions using multiply scattered light.
AB  - The isotropic scattering coefficients of 143-nm diameter polystyrene latex
      suspensions were measured using frequency-domain photon migration (FDPM) at 687
      and 828 nm as a function of volume fraction (0.05-0.3) and ionic strength (1.0 to
      120 mM NaCl equivalents) in order to derive the angle-integrated structure
      factor, S(q), and structure factor at zero wave vector, S(0). The effective
      surface charges of the dispersions were estimated by fitting the measured
      isotropic scattering coefficients at each wavelength as a function of volume
      fraction to the solution of the Orstein-Zernike integral equation using the hard
      sphere Yukawa potential model and mean spherical approximation as a closure
      relation. The estimates of surface charges were comparable at both wavelengths,
      but decreased with ionic strength. At 120 mM NaCl equivalents, the values of S(0)
      obtained from FDPM matched those predicted by the Percus-Yevick model, and
      decreased with volume fraction, consistent with prediction by the Carnahan
      Starling equation.

PMID- 16290752
TI  - A comparative study on photo-induced electron transfer from fluorescein to
      anthraquinone and injection into colloidal TiO2.
AB  - A dyad-anthraquinone-methyl ester of fluorescein-and its model compound-butyl
      ester-were synthesized. The effects of photo-induced electron transfer from
      fluorescein to an organic anthraquinone acceptor and injection into inorganic
      colloidal TiO(2) were studied respectively. It is found that the photo-induced
      electron transferring to an organic acceptor is much faster than injecting into
      inorganic colloidal particles when fluorescein was excited by visible light.
      While inorganic colloidal TiO(2) was excited by UV, the electron of fluorescein
      will inject into TiO(2).

PMID- 16290753
TI  - Study on laminar viscosity and zero shear viscosity of latex systems.
AB  - The flowing nature and rheological properties of polymethyl methacrylate latex
      systems in a coaxial cylinder viscometer were studied on the basis of laminar
      shear flow model and rheological experimental data. The physical meaning of
      laminar viscosity (eta(i,j)) and zero shear viscosity (eta(0)) were described. We
      assumed that laminar shear flows depended on position and shear time, so
      microrheological parameters were the function of position and shear time.
      eta(i,j) was the viscosity of any shear sheet i between two neighboring laminar
      shear flows at time t; j was denoted as j=t/Deltat; and Deltat was the
      interacting time of two particles or two laminar shear flows. tau(i,j) and
      gamma(i,j) were shear stress and shear rate of any shear sheet i at j moment.
      According to Newton regulation tau(i,j)=eta(i,j)gamma(i,j), apparent viscosity
      eta(a) should be a statistically mean value of j shear sheets laminar viscosity
      at j moment, i.e., eta(a)= summation operator(i=j)eta(i,j)gamma(i,j)/ summation
      operator(i=j)gamma(i,j). eta(0) was defined as shear viscosity between a laminar
      shear flow and a still fluid surface, i.e., eta(0)=(tau(i,j)/gamma(i,j))(j-i-
      >0). These new ideas described above may be helpful in the study of the
      micromechanisms of latex particle systems and worthy of more research.

PMID- 16290755
TI  - A study of the alumina-silica gel adsorbent for the removal of silicic acid from
      geothermal water: increase in adsorption capacity of the adsorbent due to
      formation of amorphous aluminosilicate by adsorption of silicic acid.
AB  - Two kinds of adsorbents (Si adsorbent and Al adsorbent) for the removal of
      silicic acid from geothermal water to retard the formation of silica scales were
      prepared using silicic acid contained in geothermal water. The Si adsorbent was
      prepared by evaporating geothermal water, and the Al adsorbent was prepared by
      evaporating geothermal water after the addition of aluminum chloride. The
      specific surface area of the Si adsorbent was small and it's adsorption capacity
      of silicic acid was low. Although the specific surface area of the Al adsorbent
      was also small, it was significantly increased by the adsorption of silicic acid
      and it's adsorption capacity was high. Based on the change in the local structure
      of aluminum ion by the adsorption of silicic acid, the Al adsorbent was
      considered to be silica particles covered with crystalline aluminum hydroxide.
      Moreover, it was concluded that the increase in the specific surface area of the
      Al adsorbent and the decrease in the zeta potential were due to the formation of
      an amorphous aluminosilicate with a large surface area and a negative charge (one
      4-coordinated Al) by the reaction between aluminum ions and silicic acids.

PMID- 16290757
TI  - Acidity and alkali metal adsorption on the SiO2-aqueous solution interface.
AB  - The intrinsic deprotonation constant (pK(a(2))(int)) and the intrinsic ion
      exchange constants (pK(Me(+))(int)) of Li(+), Na(+), and K(+) on SiO(2) were
      uniquely determined at 30 degrees C by using the potentiometric titration data,
      the Gouy-Chapman-Stern-Grahame (GSCG) model for the structure of the electrical
      double-layer (edl) and the double-extrapolation method. The values of these
      constants were pK(a(2))(int) = 6.57, pK(Li(+))(int) = pK(Na(+))(int) =
      pK(K(+))(int) = 5.61. The chemical meaning of intrinsic equilibrium constants and
      the equality in the values of pK(Li(+))(int), pK(Na(+))(int) and pK(K(+))(int)
      were discussed.

PMID- 16290758
TI  - Adsorption of a diverse set of organic vapors on the bulk water surface.
AB  - The bulk water surface is of fundamental interest to physical as well as
      environmental chemistry. As there is a lack of wide-ranging adsorption data from
      the air to the bulk water surface, a large and diverse data set of adsorption
      coefficients of nonionic, organic compounds has been produced with inverse gas
      chromatography. The 61 compounds were chosen to cover a large range of
      properties, considering the intermolecular interactions between the compounds and
      the bulk water surface, i.e., van der Waals and electron-donor/acceptor
      interactions. The data set gained in this work was interpreted with a linear free
      energy relationship (LFER) based on these intermolecular interactions. From this
      LFER, a general adsorption model is derived, including compound (i) and surface
      (surf) properties: log K(i surf/air)(m(3)/m(2)) = 0.135(+/-0.003) log K(i
      hexadecane/air)(gamma(surf)(vdW))(0.5) + 5.11(+/-0.15)Sigma beta(i2)(H)EA(surf) +
      3.60(+/-0.28)Sigma alpha(i2)(H)ED(surf) - 8.47. This adsorption model can be used
      for the characterization of adsorption to any other surface. The adsorption model
      for bulk water surface adsorption as well as the general adsorption model can be
      used as prediction tools in natural or technical systems.

PMID- 16290756
TI  - The sorption of divalent metal ions on AlPO4.
AB  - The sorption of Cu(2+), Pb(2+), Ni(2+), and Cd(2+) ions on the aluminum(III)
      phosphate was observed to increase with increases in the concentration,
      temperature, and pH of the system. The apparent dissociation (pK(a)), binding
      (pK(b)) and exchange (pK(ex)) constants of aluminum(III) phosphate were evaluated
      and found to be dependent upon the temperature and nature of the metal cations.
      The values of the dissociation constants (pK(a)) followed the order
      Pb(2+)<Cu(2+)<Cd(2+)<Ni(2+)<K(+), opposite to the values of the binding constants
      and selectivity shown by the solid. Ion exchange between protons from the surface
      and metal cations from aqueous solution was found to be responsible for the metal
      ions sorption by AlPO(4). The values of the dissociation (pK(a)) and exchange
      (pK(ex)) constants were used to estimate the corresponding apparent thermodynamic
      parameters (DeltaH(o)(diss), DeltaS(o)(diss) and DeltaH(o)(exch),
      DeltaS(o)(exch)). The values of DeltaH(o)(diss) and DeltaH(o)(exch) were found to
      be positive, which showed that both the dissociation and exchange processes were
      endothermic in nature. The DeltaS(o)(diss) and DeltaS(o)(exch) were also found to
      be positive, which showed that both the deprotonation and exchange processes on
      the AlPO(4) were entropy driven and spontaneous.

PMID- 16290759
TI  - Adsorption of a diverse set of organic vapors on quartz, CaCO3, and alpha-Al2O3
      at different relative humidities.
AB  - Adsorption constants of a diverse set of 50 organic vapors have been measured on
      quartz (SiO(2)), CaCO(3), and alpha-Al(2)O(3) at different relative humidities at
      15 degrees C. For nonpolar compounds we found an exponential decrease of the
      adsorption constants on a given mineral between 40 and 97% relative humidity.
      Extrapolated to 100% relative humidity, the adsorption constants of nonpolar
      compounds on the different minerals coincide and agree with those measured on a
      bulk water surface. The adsorption constants of polar compounds also decrease
      with increasing humidity up to 90%, but between 90% and 100% they increase again.
      We speculate that this effect is due to a change in the orientation of the water
      molecules that form the surface at which the organic vapors adsorb at this high
      humidity. The compound variability in the adsorption constants of all compounds
      on a given surface at a given relative humidity could be described rather well
      with a linear free energy relationship using Abraham's solvation parameters for
      the van der Waals and electron-donor/acceptor properties of the compounds. The
      remaining deviation between fitted and experimental data was found to be
      systematic, which indicated that an optimized parameter set for the used
      compounds could still considerably improve the fit.

PMID- 16290760
TI  - Electrokinetic and thermodynamic analysis of the adsorption process of N
      cetylpyridinium chloride on polyester fabric.
AB  - An electrokinetic and thermodynamic analysis of the adsorption process of N
      cetylpyridinium chloride on polyester fabric is described in the present work.
      The electrokinetic study was performed by means of electrophoretic mobility
      measurements of the polyester-surfactant system. The most significant result is
      the increase in electrokinetic potential, zeta, toward more positive values as
      the surfactant concentration in the dispersion medium is raised. Given the
      molecular structure of N-cetylpyridinium chloride (N-CP-Cl), which contains a
      pyridinium group, positively charged, it is feasible that such increase in |zeta|
      is due to the electrostatic attraction between the carboxyl groups of polyester,
      ionized at pH 8.5, and the pyridinium group of the surfactant. The uptake of N-CP
      Cl by the fiber is experimentally determined at four temperatures: the strong
      increase in the amount of the surfactant incorporated onto the fiber as the
      initial concentration of N-CP-Cl is larger shows that the electrostatic
      attraction between the fiber and the surfactant is the main mechanism of the
      adsorption of the surfactant onto the fiber. The obtained data on the kinetics
      and thermodynamics of adsorption of N-cetylpyridinium chloride onto the
      polyester, standard free energy, enthalpy, and entropy related to the process of
      adsorption are in accordance with our hypothesis on the mechanisms of adsorption.
      From a different point of view, the efficient coverage of polyester by N-CP-Cl is
      also demonstrated by the changes experienced by the surface free energy of
      polyester upon treatment with N-CP-Cl.

PMID- 16290761
TI  - Immobilization of antibodies on glass surfaces through sugar residues.
AB  - This work characterizes substrates for immunoassays obtained through the
      immobilization of vectorially oriented antibodies on glass. The method of
      preparation is based on the condensation reaction between an aldehyde group on
      the F(c) portion of antibodies and the hydrazide group on the modified glass
      surface. Light microscopy and AFM imaging in height and phase modes were used to
      assess the properties of the modified surface. Both techniques are consistent
      with a fairly uniform antibody coverage on the micrometer and submicrometer
      scales. ELISA tests were used to evaluate the activity and surface distribution
      of immobilized antibodies as well as nonspecific binding to surfaces after
      various modification steps. It was shown that exposure of the surfaces to a BSA
      solution minimized nonspecific binding to undetectable levels.

PMID- 16290762
TI  - Synthesis and characterization of oligomaltose-grafted lipids with application to
      liposomes.
AB  - Novel glycolipids, which contain 2 and 15 oligomaltose units and a
      phosphatidylethanolamine, were synthesized and characterized by FTIR and (1)H-NMR
      spectroscopies. The well-defined linear structure of the glycolipids was assured
      by an end-point conjugation strategy using selective oxidation of the reducing
      end groups of maltose oligosaccharides, followed by aminolysis with
      distearoylphosphatidylethanolamine. The intermediate acids react selectively with
      amines to form amide linkages, catalyzed by 1-ethyl-3-(3-dimethylaminopropyl)
      carbodiimide hydrochloride and N-hydroxysuccinimide. Conformations of the
      glycolipids at the air-water interface were proposed based on the film balance
      measurements. The unique conformations of glycolipids at interfaces may offer
      advantages over traditional PEO-derived lipids in regard to their applications
      for sterically stabilizing liposomes. The glycolipids demonstrated the ability
      for sterically stabilizing liposome dispersions, as determined by turbidity
      measurements.

PMID- 16290764
TI  - Preparation and characterization of polyvinyl alcohol-capped CdSe nanoparticles
      at room temperature.
AB  - Polyvinyl alcohol (PVA)-capped CdSe nanoparticles were successfully prepared by a
      one-step solution growth technique at room temperature and ambient pressure. X
      ray diffraction, transmission electron microscopy, infrared spectra, and X-ray
      photoelectron spectra were used to characterize the final product. The as
      prepared CdSe nanocrystals were well dispersed and uniform in shape and the
      diameter of the particles was confined within 8 nm. Ultraviolet-visible
      absorption spectra were used to study the confined growth process of PVA-capped
      CdSe nanoparticles. Photoluminescence measurement showed the near band-edge
      luminescence of the final product.

PMID- 16290763
TI  - The mechanism of hemolysis by surfactants: effect of solution composition.
AB  - The effect of ionic strength, solute size, and osmolarity of the suspending
      solution on surfactant-induced erythrocyte hemolysis was studied. Two possible
      mechanisms of hemolysis were considered: osmotic lysis (affected by solute
      particle size) and solubilization (not affected by solute particle size). It was
      found that the ionic strength of the solution has a major effect on the hemolysis
      process, depending on the surfactant nature and concentration. An increase in the
      ionic strength lowers the rate of hemolysis induced by DTAB, and enhances SDS
      induced hemolysis. Changes in ionic strength have little effect on hemolysis
      induced by Triton X-100. To explain these effects, it was assumed that the
      changes in ionic strength differently affect the adsorption of cationic and
      anionic surfactants to the membrane. The change in the amount of adsorbed
      surfactant either influences the rate of osmotic hemolysis by changing the
      membrane permeability or induces a transition from the osmotic mechanism to
      solubilization. These phenomena were observed for isotonic as well as hypertonic
      solutions.

PMID- 16290765
TI  - Inorganic-organic hybrid nanoparticles from n-octyl triethoxy silane.
AB  - Ormosil (organically modified silane) such as n-octyl triethoxy silane has been
      found to aggregate in the form of normal micelles as well as reverse micelles in
      which the triethoxy silane moeities are hydrolyzed to form a hydrated silica
      network while the n-octyl groups are held together through hydrophobic
      interaction. These nanoparticles are spherical in shape and are nearly
      monodispersed with an average diameter of below 100 nm. The nanoparticles
      originating from the micellar aggregate have an hydrophobic core with a layer of
      the hydrated silica network at the surface. The hydrophobic core can host
      hydrophobic molecules such as tetraphenyl porphyrin, which is leached out of the
      particles extremely slowly compared to that in Triton X-100 micelles. The
      nanoparticles originating from the reverse micelles have a hydrated silica
      network in the core surrounded by the hydrophobic n-octyl chains on the particle
      surface. The hydrophilic silica cores of these nanoparticles have been used to
      encapsulate horseradish peroxidase (HRP) and the enzyme shows its activity and
      follows Michaelis-Menten kinetics.

PMID- 16290766
TI  - Dithiol-mediated immobilization of CdS nanoparticles from reverse micellar system
      onto Zn-doped silica particles and their high photocatalytic activity.
AB  - Cds nanoparticles, prepared in a reverse micellar system, were immobilized
      directly onto alkanedithiol-modified Zn-doped silica particles, which were
      themselves prepared via hydrolysis of tetraethylorthosilicate in the presence of
      Zn(NO(3))(2) followed by contact with dithiol molecules. The resulting CdS-Zn
      SiO(2) composite was then used as a photocatalyst for the generation of H(2) from
      2-propanol aqueous solution. Under UV irradiation (lambda>300 nm), a high
      photocatalytic activity was observed for the CdS-Zn-SiO(2) composite material.
      This is effected by electron transfer from the photoexcited ZnS (dithiol-bonded
      Zn on SiO(2)) to CdS nanoparticles. The photocatalytic activity is increased with
      a decrease in the number of methylene groups in the dithiol molecules, according
      to the rank order 1,10-decanedithiol <1,6-hexanedithiol <1,2-ethanedithiol.

PMID- 16290767
TI  - Polyvinylpyrrolidone adsorption and structural studies on homoionic Li-, Na-, K-,
      and Cs-montmorillonite colloidal suspensions.
AB  - Structural aspects of dilute homoionic Li-, Na-, K-, and Cs-montmorillonite (M
      montmorillonite) particle suspension (1 g/L) under low-electrolyte-concentration
      (0.1 mM MCl) conditions were characterized by static (absorbance or turbidity)
      and dynamic (photon correlation spectroscopy) light-scattering methods as well as
      by the adsorption behaviors of nonionic polyvinylpyrrolidone (PVP) mol wt 5,000
      g/mol (LMW PVP) and mol wt 400,000 g/mol (HMW PVP). Taking Li-montmorillonite as
      a reference for a single plate particle, a particle size increase and a surface
      accessibility decrease to polymer adsorptions were measured along the Li, Na, K,
      and Cs series. The results are related to the existence of montmorillonite
      quasicrystals or tactoids in diluted suspension, whose stability increases along
      the same cation series. Molecular weight effects on the PVP surface accessibility
      are discussed in terms of permeation properties of the different M
      montmorillonite particles. Modeling the results calculates an average number of
      plates in montmorillonite quasi-crystals and the surface area distribution of
      ultramicropores <0.7 nm and pores >0.7 nm in M-montmorillonite particles. It can
      also be demonstrated by applying hydrodynamic and electrokinetic methods that the
      measured high absorbance or turbidity increase of PVP-loaded montmorillonite
      particles is not due to aggregation phenomena but to a PVP contribution in the
      light-scattering intensity.

PMID- 16290768
TI  - Stability of dispersions of colloidal hematite/yttrium oxide core-shell
      particles.
AB  - The colloidal stability of suspensions of hematite/yttria core/shell particles is
      investigated in this work and compared with that of the pure hematite cores. The
      different electrical surface characteristics of yttrium and iron oxides, as well
      as the diameters of both types of spherical particles, dominate the overall
      process of particle aggregation. The aggregation kinetics of the suspensions was
      followed by measuring their optical absorbance as a function of time. By
      previously calculating the extinction cross section of particle doublets, it was
      demonstrated that for both core and core/shell particles the turbidity of the
      suspensions should increase on aggregation. Such an increase was in fact found in
      the systems in spite of the ever-present tendency of the particles to settle
      under gravity. The authors used the initial slope of the turbidity increment time
      plots as a measure of the ease of aggregation between particles. Thus, they found
      that the essential role played by pH on the charge generation on the two oxides
      and the shift of one pH unit between the isoelectric points of hematite and
      yttria manifest in two features: (i) the stability decreases on approaching the
      isoelectric point from either the acid or basic side and (ii) the maximum
      instability is found for hematite at pH 7 and for hematite/yttria at pH 8, that
      is, close to the isoelectric points of alpha-Fe(2)O(3) and Y(2)O(3),
      respectively. The role of added electrolyte is simply to yield the suspensions of
      either type more unstable. Using the surface free energy of the particles, the
      authors could estimate their Hamaker constants in water. From these and their
      zeta potentials, the DLVO theory of stability was used to quantitatively explain
      their results.

PMID- 16290769
TI  - Characteristics of modified Cab-O-Sil in aqueous media.
AB  - Fumed silica Cab-O-Sil HS-5 grafted with 3-aminopropyldimethylsilyl (APDMS),
      butyldimethylsilyl (BDMS), octadecyldimethylsilyl (ODDMS), and trimethylsilyl
      (TMS) groups of different concentrations were studied using photon correlation
      spectroscopy, electrophoresis, potentiometric titration, and nitrogen adsorption
      methods. Calculations of both electrophoretic mobility and zeta potential were
      performed taking into consideration the topological structure of "porous"
      aggregates of primary particles of fumed silica using two different approaches.
      Changes in surface charge density and the textural, aggregative, and
      electrophoretic characteristics of modified silicas depend on the type of grafted
      OSC, its chain length, polarity, and surface concentration. Particle swarms of
      initial and modified silicas in aqueous suspension are typically characterized by
      bimodal size distributions between 20 and 300 nm (aggregates) and 1-3 microm
      (agglomerates of aggregates). The difference between parameter values computed
      according to the Smoluchowski theory and improved approaches increases with
      increasing pH and is concordant for both mobility and zeta potential.

PMID- 16290770
TI  - Modified Henry function for the electrophoretic mobility of a charged spherical
      colloidal particle covered with an ion-penetrable uncharged polymer layer.
AB  - An approximate expression is derived for the electrophoretic mobility of a
      spherical charged colloidal particle carrying low zeta potential covered with an
      ion-penetrable uncharged polymer layer in an electrolyte solution. This
      expression, which becomes Henry's mobility formula in the absence of the polymer
      layer, is a modification of Henry's mobility formula by taking into account the
      presence of the uncharged polymer layer.

PMID- 16290771
TI  - Electrokinetics of concentrated suspensions of spherical colloidal particles with
      surface conductance, arbitrary zeta potential, and double-layer thickness in
      static electric fields.
AB  - In this paper the electrophoretic mobility and the electrical conductivity of
      concentrated suspensions of spherical colloidal particles have been numerically
      studied under arbitrary conditions including zeta potential, particle volume
      fraction, double-layer thickness (overlapping of double layers is allowed),
      surface conductance by a dynamic Stern layer model (DSL), and ionic properties of
      the solution. We present an extensive set of numerical data of both the
      electrophoretic mobility and the electrical conductivity versus zeta potential
      and particle volume fraction, for different electrolyte concentrations. The
      treatment is based on the use of a cell model to account for hydrodynamic and
      electrical interactions between particles. Other theoretical approaches have also
      been considered for comparison. Furthermore, the study includes the possibility
      of adsorption and lateral motion of ions in the inner region of the double layers
      (DSL model), according to the theory developed by C. S. Mangelsdorf and L. R.
      White (J. Chem. Soc. Faraday Trans.86, 2859 (1990)). The results show that the
      correct limiting cases of low zeta potentials and thin double layers for dilute
      suspensions are fulfilled by our conductivity formula. Moreover, the presence of
      a DSL causes very important changes, even dramatic, on the values of both the
      electrophoretic mobility and the electrical conductivity for a great range of
      volume fractions and zeta potentials, specially when double layers of adjacent
      cells overlap, in comparison with the standard case (no Stern layer present). It
      can be concluded that in general the presence of a dynamic Stern layer causes the
      electrophoretic mobility to decrease and the electrical conductivity to increase
      in comparison with the standard case for every volume fraction, zeta potential,
      and double-layer thickness.

PMID- 16290772
TI  - Interactions between acid- and base-functionalized surfaces.
AB  - In this paper we present an AFM force study on interactions between chemically
      modified surfaces. Surfaces with terminal groups of either NH(2) or COOH were
      obtained by chemisorption of a silane-based compound (3-amino
      propyltriethoxysilane) on silica or a thiol compound (11-mercapto undecanoic
      acid) on gold. The surfaces were characterized by streaming potential and contact
      angle measurements. For the NH(2) surfaces the density of functional groups
      strongly depends on the pretreatment of the silica. Both the NH(2) and COOH
      surfaces show a steady and ongoing loss of functional groups, but on the time
      scale of our force measurements they can be considered to be stable. Interaction
      curves for the various combinations of surfaces in aqueous solutions show a
      strong correlation with the ionization state of the surface groups. The approach
      curves can be explained on the basis of electrostatic interactions. On retraction
      a pH-dependent adhesion is found, the strongest being between NH(2) and COOH
      surfaces as a result of acid-base interactions. Between NH(2) layers and between
      COOH layers there is also adhesion, due to the formation of H bonds. The
      corresponding work of adhesion W was calculated using the DMT (Derjaguin, Muller,
      Toporov) equation. The values of W obtained are small compared to literature data
      and suggest that only a fraction of the functional groups in the contact area is
      involved in acid-base or H-bond interactions. This is attributed mainly to the
      roughness of the surfaces, which substantially reduces adhesion. A rough estimate
      is made for the rupture force of the NH(2)-COOH acid-base bond in water.

PMID- 16290773
TI  - Disjoining pressure isotherms of water-in-bitumen emulsion films.
AB  - In the oil sands industry, undesirable water-in-oil emulsions are often formed
      during the bitumen recovery process where water is used to liberate bitumen from
      sand grains. Nearly all of the water is removed except for a small percentage
      (approximately 1 to 2%), which remains in the solvent-diluted bitumen as
      micrometer-sized droplets. Knowledge of the colloidal forces that stabilized
      these water droplets would help to increase our understanding of how these
      emulsions are stabilized. In this study, the thin liquid film-pressure balance
      technique has been used to measure isotherms of disjoining pressure in
      water/toluene-diluted bitumen/water films at five different toluene-bitumen mass
      ratios. Even though a broad range of mass ratios was studied, only two isotherms
      are obtained, indicating a possible change in the molecular orientation of
      surfactant molecules at the bitumen/water interfaces. At low toluene-bitumen mass
      ratios, the film stability appears to be due to a strong, short-range steric
      repulsion created by a surfactant bilayer. Similar isotherms were obtained for
      water/toluene-diluted asphaltene/water films, indicating that the surface active
      material at the interface probably originated from the asphaltene fraction of the
      bitumen. However, unlike the bitumen films, films of toluene-diluted asphaltenes
      often formed very rigid interfaces similar to the "protective skin" described by
      other researcher.

PMID- 16290774
TI  - Impurity distribution in a solid-liquid interface during static layer
      crystallization.
AB  - The impurity distribution inside crystalline layers in static layer
      crystallizations was explored theoretically and experimentally for a binary
      eutectic mixture of caprolactam and water. The impurity distribution in the layer
      is modeled by a mass balance equation coupled with an energy balance equation.
      The mass balance equation is established with a combination of the growth of the
      layer and the diffusional movement of impurity. The mathematical model was solved
      by a numerical method. The predictions are discussed with respect to the
      interfacial distribution coefficient, concentration, and temperature at the solid
      liquid interface, crystalline layer thickness, and concentration of the layer.
      The impurity distribution obtained by the model was appropriately verified with
      the results obtained by the experiments.

PMID- 16290776
TI  - The pore structure in processed Victorian Brown coal.
AB  - Changes in the pore structure of Victorian Brown coal when upgraded with heated
      gases under pressure are investigated. We show that the results obtained from
      ultra-small-angle neutron scattering (USANS) measurements agree with previous
      results using small-angle X-ray scattering results but that USANS may also be
      used to investigate the meso porosity. Findings from small-angle scattering are
      confirmed using electron microscopy. We also show evidence from electron
      diffraction that thermal conditions within the brown coals during the upgrade
      procedure may be far more extreme than previously thought.

PMID- 16290775
TI  - Porous texture evolution in Nomex-derived activated carbon fibers.
AB  - In the present work, the textural evolution of a series of activated carbon
      fibers with increasing burn-off degree, prepared by the pyrolysis and steam
      activation of Nomex aramid fibers, is followed by measurements of physical
      adsorption of N(2) (77 K) and CO(2) (273 K) and immersion calorimetry into
      different liquids (dichloromethane, benzene, cyclohexane). The immersion
      calorimetry results are discussed in depth, paying special attention to the
      choice of the reference material. The activated carbon fibers studied possess an
      essentially homogeneous microporous texture, which suggests that these materials
      may be applied in gas separation, either directly or with additional CVD
      treatment.

PMID- 16290777
TI  - Coating of Y2O3:Eu3+ particles with alumina by a humid solid state reaction at
      room temperature.
AB  - Humid solid state reaction at room temperature was utilized for the first time to
      coat Y(2)O(3):Eu(3+) particles with alumina. The particles were studied with an X
      ray photoelectron spectrometer (XPS), a scanning electron microscope (SEM), and
      an energy dispersive spectrometer (EDS). XPS results show that the yttrium and
      europium contents are decreased and that the aluminum content is the highest
      except for that of oxygen after coating. SEM and EDS results show that particles
      are coated with a thin shell of alumina.

PMID- 16290778
TI  - H2S adsorption/oxidation on materials obtained using sulfuric acid activation of
      sewage sludge-derived fertilizer.
AB  - Sewage sludge-derived fertilizer, Terrene, was used as a precursor of adsorbents
      tested for removal of hydrogen sulfide from moist air. The adsorbents were
      obtained by pyrolysis of sulfuric acid-treated granular fertilizer at 600, 800,
      and 950 degrees C in a nitrogen atmosphere. The highest H(2)S removal capacity
      was obtained for the sample carbonized at 950 degrees C. This is a result of a
      combined effect of the specific chemistry of the inorganic phase and the
      development of microporosity within the carbon deposit. On the surface of the
      materials studied hydrogen sulfide is converted to elemental sulfur, sulfides,
      and sulfates as a result of the reaction with salts/oxides and the presence of an
      oxidizing atmosphere. The pores are gradually filled as the surface reactions
      proceed. The removal of H(2)S occurs until all the small micropores are filled
      with the reaction/oxidation products.

PMID- 16290779
TI  - Aggregated assemblies of sodium dodecyl sulfate/dimethyldodecyl ammoniopropane
      sulfonate and phospholipids at the interface and in the bulk.
AB  - Interactions between the binary combinations of sodium dodecyl sulfate (SDS) or
      dimethyldodecylammoniopropane sulfonate (DPS) with L-alpha-phosphatidylcholine
      (PC), 1,2-didecanoyl-sn-glycero-3-phosphacholine (DPC), and 1,2-dipalmitoyl-sn
      glycero-3-phosphacholine (PPC) at the air/water interface and in aqueous bulk
      were evaluated with the help of interfacial tension (gamma) and pyrene
      fluorescence (I(1)/I(3)) measurements by studying the aggregation processes of
      SDS and DPS in pure water and in the presence of 7-36 microM of each lipid. The
      gamma measurements suggested that the interface was mainly occupied by the
      surfactant monomers especially in the presence of PC and PPC, and the surfactant
      PC or surfactant-PPC aggregates were mainly available in the bulk with the least
      surface activity. Significant surface activity was observed in the case of a
      surfactant-DPC complex. The fluorescence measurements showed clear onset, C(1),
      and completion, C(2), of a vesicles solubilization process upon incorporation of
      surfactant monomers into the vesicles in the presence of DPC and PPC whereas this
      process was not visible in the presence of PC. A comparative study of all the
      three lipids indicated that both PC and PPC were mainly available in the
      aggregated form in the bulk due to their higher hydrophobicities and, hence, were
      the least surface active. On the other hand, DPC with relatively lower
      hydrophobicity showed considerable surface activity even in the monomeric form.
      Among both surfactants, DPS showed stronger interactions with DPC and PPC in
      comparison to SDS due to its zwitterionic nature, which could easily accommodate
      itself into the lipid-aggregated assemblies with similar headgroup natures, and
      helped in reducing the interhead-group repulsions.

PMID- 16290780
TI  - Kinetics of disproportionation of air bubbles beneath a planar air-water
      interface stabilized by food proteins.
AB  - The rate of shrinkage of air bubbles of initial radii, r, from 50 to 150 microm
      injected beneath a planar air-water interface has been measured. Bubbles were
      stabilized by 0.05 wt% protein in approximately 0.1 mol dm(-3) ionic strength
      buffer at pH 7.0 and at room temperature. Four proteins were studied: commercial
      whey protein isolate (WPI), sodium caseinate, gelatin, and pure beta
      lactoglobulin. Bubbles in all systems showed shrinkage due to diffusion of gas
      from the bubbles, which accelerated as the bubbles got smaller. Within
      approximately 1 h all bubbles had disappeared, having shrunk to below
      approximately 1 microm, so that in no cases was there evidence of stabilization
      via a surface rheological mechanism. The rates of shrinkage with the different
      proteins were not significantly different except in the case of gelatin, which at
      any given bubble size appeared to give a slightly higher rate, probably because
      the surface tension is higher for this system. A new theoretical analysis of the
      dissolution kinetics for the case of a bubble close to a planar interface has
      been developed. For caseinate and WPI a simple model incorporating a constant
      surface tension and a constant bubble-interface separation appears to account for
      the kinetics. Interestingly, the model predicts a linear dependence of r(n)
      versus time when n is closest to 3, in contrast to n = 2 expected from previous
      work. For gelatin and pure beta-lactoglobulin, the introduction of modest
      dilatational elasticities of approximately 2.3 and 7 mN m(-1), respectively,
      gives good agreement between theory and experiment. This is particularly the case
      for beta-lactoglobulin, where there is a noticeable slowing, but not cessation,
      of the shrinkage as the bubbles get smaller. In the light of these findings the
      practical significance of surface rheology with respect to stability to
      disproportionation is discussed. Finally, we present experimental evidence that a
      bubble stabilized by beta-lactoglobulin shrinks to a nonspherical protein
      particle consisting of the completely collapsed protein film.

PMID- 16290781
TI  - Rapid separation of oil particles from low-concentrated O/W emulsions in the
      presence of anionic surfactants using fibrous slag.
AB  - Rapid removal of low-concentrated oil from stable O/W emulsions has been one of
      the most difficult techniques, and an effective method has not yet been
      established so far. Our novel technique using surface characteristics, the
      application of a heterocoagulation phenomenon, is a good alternative for
      separating colloidal particles. In this research, the rapid separation of n
      decane oil droplets in the presence of sodium dodecyl sulfate (SDS) by a column
      bed packed with fibrous ferro-nickel slag (FS) was investigated. Separation of
      emulsified n-decane droplets was examined at SDS concentrations ranging from 0 to
      1.0x10(-4) M, and the results were discussed in terms of electric interfacial
      interaction of both an n-decane droplet and a collector medium. When the SDS
      concentration was 3.0x10(-5) M or lower, n-decane droplets were efficiently
      collected by FS, and the coalescence between approaching and already-deposited
      oil particles promoted the oil collection. When the SDS concentration was higher
      than 3.0x10(-5) M, however, the n-decane collection ratio monotonically decreased
      with time, indicating that n-decane droplets attached to the FS surface. These
      experimental findings were in qualitative agreement with the DLVO theory and
      suggested that separation using surface characteristics is a promising method for
      the recovery of stable emulsified oil droplets.

PMID- 16290782
TI  - Supramolecular self-assembly of nanotubes and supercoils from long-chain
      derivatives of pyrimindinetrione and triazine.
AB  - The self-assembly of two complementary components, 5-(4-N-methyl-N
      dodecylaminobenzylidene)-2,4,6-(1H,3H)-pyrimidi-netrione (1) and 4-amino-2,6
      didodecylamino-1,3,5-triazine (2) was found to result in the formation of a
      hollow supramolecular nanotube with about 6 nm in diameter and hundreds of
      nanometers in length as observed directly by transmission electron microscope
      (TEM). X-ray diffraction patterns indicate that a periodical layered structure
      with a d spacing of 0.49 nm in the nanotube exists. If staining treatment were
      employed in TEM observations, the self-assembly was found to show a supercoil
      structure about 300 nm in diameter.

PMID- 16290784
TI  - A numerical study of the effect of insoluble surfactants on the stability of a
      viscous drop translating in a Hele-Shaw cell.
AB  - A circular drop is a linearly stable solution for the buoyancy-driven motion of
      drops in a Hele-Shaw cell [Gupta et al. J. Colloid Interface Sci.218(1), 338
      (1999)]. In the absence of surface-active agents, an initially prolate drop
      always goes to a steady circular shape while initially oblate drops exhibit
      complex dynamics [Gupta et al. J. Colloid Interface Sci.222, 107 (2000)]. In this
      study, the effect of insoluble surfactant impurities on the critical conditions
      for drop breakup is explored by using the Langmuir adsorption framework in
      conjunction with a physically based expression for the depth-averaged tangential
      stress exerted on a two-phase interface in a Hele-Shaw cell. It is shown that the
      presence of surfactants can have both a stabilizing and a destabilizing effect on
      the shape of the drop, depending on the Bond number, the magnitude of the initial
      perturbation, and the strength of surface convection. Similar to the clean drop
      dynamics, two marginally stable branches are found. Increasing the surface Peclet
      number results in the stabilization of the main branch while the secondary branch
      shifts to higher Bond numbers. The mode of breakup is also found to be strongly
      influenced by the strength of surface convection.

PMID- 16290785
TI  - Effect of chemical treatment of Kevlar fibers on mechanical interfacial
      properties of composites.
AB  - In this work, the effects of chemical treatment on Kevlar 29 fibers have been
      studied in a composite system. The surface characteristics of Kevlar 29 fibers
      were characterized by pH, acid-base value, X-ray photoelectron spectroscopy
      (XPS), and FT-IR. The mechanical interfacial properties of the final composites
      were studied by interlaminar shear strength (ILSS), critical stress intensity
      factor (K(IC)), and specific fracture energy (G(IC)). Also, impact properties of
      the composites were investigated in the context of differentiating between
      initiation and propagation energies and ductile index (DI) along with maximum
      force and total energy. As a result, it was found that chemical treatment with
      phosphoric acid solution significantly affected the degree of adhesion at
      interfaces between fibers and resin matrix, resulting in improved mechanical
      interfacial strength in the composites. This was probably due to the presence of
      chemical polar groups on Kevlar surfaces, leading to an increment of interfacial
      binding force between fibers and matrix in a composite system.

PMID- 16290783
TI  - Effect of pharmaceutically acceptable glycols on the stability of the liquid
      crystalline gels formed by Poloxamer 407 in water.
AB  - The ability of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)
      (PEO-PPO-PEO) block copolymers (Poloxamers) to form "gels" (lyotropic liquid
      crystalline structures) in water is of interest to pharmaceutical applications.
      In such applications the presence of polar organic solvents is often desirable or
      required. The effect of such solvents on the stability of lyotropic liquid
      crystalline gels formed by PEO-PPO-PEO block copolymers was assessed by studying
      the phase behavior and structure in ternary isothermal (25 degrees C) systems of
      pharmaceutical interest consisting of Poloxamer 407 (EO(100)PO(70)EO(100)),
      water, and one of the following solvents (referred to here collectively as
      "glycols"): glycerol, propylene glycol, ethanol, polyethylene glycol 400, and
      glucose. Small-angle X-ray scattering was employed to establish the structure of
      the liquid crystals obtained and to determine their characteristic length scales.
      The stability range of the liquid crystalline gel phases in the systems studied
      was found to vary with the glycol type. For example, the micellar cubic structure
      can accommodate about 0.85:1 parts glucose per part water (in terms of weight)
      and up to as much as 5.5:1 parts propylene glycol per part water. A correlation
      between the glycol effects on the stability of the liquid crystalline phases and
      glycol physiochemical characteristics such as octanol/water partition coefficient
      or solubility parameter is proposed.

PMID- 16290786
TI  - Random sequential adsorption kinetics of dimers and trimers on geometrically
      disordered substrates.
AB  - A study is made by means of Monte Carlo (MC) simulations of the kinetics of
      random sequential adsorption (RSA) of dimers and linear and bent trimers on some
      geometrically disordered substrates. The MC data are explained by a semiempirical
      equation whose parameters interpret the jamming fraction of the process and some
      geometric characteristics of the systems studied.

PMID- 16290787
TI  - Alkanediyl-alpha,omega-bis(dimethylalkylammonium bromide) surfactants: II. Krafft
      temperature and melting temperature.
AB  - The melting temperature T(M) of two series of dimeric (gemini) surfactants, the
      alkanediyl-alpha,omega-bis(dodecyl and hexadecyl dimethylammonium bromide),
      referred to as 12-s-12 and 16-s-16, respectively (s = carbon number of the
      alkanediyl spacer), and the Krafft temperature T(K) of 1 wt% aqueous solutions of
      these surfactants have been measured. The melting temperature of the solid
      surfactant increases with the carbon number m of the alkyl chain. For each
      surfactant series, T(M) goes through a maximum at s close to 5, irrespective of
      the value of m. For the 12-s-12 series, T(M) goes through a minimum at s = 10 to
      12. At a constant value of s, the value of T(K) increases with m. The variations
      of T(M) and T(K) with s show some correlation, with T(K) decreasing when T(M)
      increases and vice versa. The results are discussed in relation to the solution
      properties of the investigated surfactants.

PMID- 16290788
TI  - Modified Dubinin-Radushkevich/Dubinin-Astakhov adsorption equations.
AB  - The Dubinin-Radushkevich/Dubinin-Astakhov (DR/DA) adsorption equations have been
      modified with the aim to eliminate the thermodynamic incorrect behavior of these
      equations in the Henry region and in the vicinity of the equilibrium saturated
      vapor pressure. The expressions for heat and entropy of adsorption are obtained
      from the proposed modified DR/DA equations. These new equations, which do not
      include additional empirical parameters, have been evaluated on adsorption
      systems measured over a wide range of pressure and temperatures. The temperature
      dependence of the parameters has been analyzed.

PMID- 16290789
TI  - Effects of acetonitrile on adsorption behavior of bovine serum albumin onto
      synthetic calcium hydroxyapatite particles.
AB  - The objective of this study was to examine the effects of acetonitrile (AN) on
      the adsorption behavior of bovine serum albumin (BSA) onto calcium hydroxyapatite
      [Ca10(PO4)6(OH)2 Ca10, Hap] materials by combining the ultraviolet (UV) and
      circular dichroism (CD) measurements of BSA solution. The structural change of
      BSA molecules with addition of AN was investigated by UV and CD spectroscopy
      measurements prior to studying adsorption behavior of BSA onto Hap. The CD
      spectra revealed that the fraction of alpha-helical content of BSA is remarkably
      decreased at AN concentrations above 30 vol.%, while beta-sheet content is
      increased. On the other hand, the percentages of random coil and turn contents
      were decreased only slightly. In addition to this secondary structural change of
      BSA, the UV spectra suggested that the tertiary structure of protein molecules
      was also changed by the addition of large amounts of AN; BSA molecules associate
      to form molecular aggregates at [AN]> or =40 vol.%. From the adsorption of BSA
      onto Hap particles (ca. 30 nm in the particle length) from a water-AN mixed
      solution, it was revealed that the adsorption behavior of BSA strongly depends on
      the change of secondary and tertiary structures of BSA by addition of AN. The
      contraction of BSA molecules at low AN concentrations (10-20 vol.%) gave their
      small cross-sectional area, providing a large amount of adsorption (n(BSA)),
      although n(BSA) was decreased above 30 vol.% AN by enlargement of BSA molecules
      with solvation and unfolding some alpha-helix domains. The n(BSA) values of the
      systems with AN exhibited a maximum; n(BSA) was increased at a lower BSA
      concentration region, although it was decreased at a higher BSA concentration due
      to self-association. Accompanying the change of n(BSA) with AN addition, the
      maxima of electrophoretic mobility (em) of the Hap particles were observed for
      the systems with AN, although the em of Hap particles was normally increased and
      saturated with increase in protein coverage for the native structure on the
      system without AN. On the other hand, because the aggregated BSA molecules could
      be cooperatively bound, the adsorption of BSA onto the Hap particles with large
      size (108 nm in the particle length) was enhanced in the presence of AN.

PMID- 16290790
TI  - Sorption of hydrophobic molecules by organic/inorganic mesostructures.
AB  - During the synthesis of micelle-templated silica an intermediate
      inorganic/organic mesostructure is obtained with an hexagonal arrangement of
      channels filled by surfactant molecules. The ability of such a mesostructure to
      solubilize organic molecules from an aqueous solution was investigated. To that
      end, silica/cationic surfactant mesostructures were prepared under various
      conditions and their stability toward surfactant release in water was first
      compared in order to select materials as stable as possible. Swelled
      mesostructures were also used. The sorption from solution of hydrophobic
      molecules was then studied. The affinity of the molecules for the mesostructures
      is directly related to their hydrophobic character as it is derived from their
      octanol/water partition coefficient. A cooperative effect between hydrophobic
      molecules and the cationic surfactant that stabilizes the surfactant inside the
      mesostructure was observed. Interaction energies between the solutes and the
      mesostructures were determined by microcalorimetry. They varied in accordance
      with the hydrophobic character of the molecule and, at low sorption amounts, they
      were of the same order of magnitude as the solubilization enthalpies in bulk
      micelles. When the sorption increases, the surfactant layer in the mesostructure
      is not allowed to swell as the free micelle does, and steric limitations in the
      headgroup area render sorption less favorable.

PMID- 16290791
TI  - Kinetic study of desorption of two species of bovine serum albumin from alumina
      during alkali elution process.
AB  - Kinetics of desorption of irreversibly adsorbed bovine serum albumin (BSA) from
      alumina (Al2O3) particles at various surface coverages (theta) was studied in a
      plug-flow column by feeding 0.05 M NaOH solution. The desorption curve obtained
      by plotting the logarithm of the amount of residual BSA against elution time was
      analyzed by using an integrated model that describes two simultaneous first-order
      processes. At each of theta, except for an initial lag time, the curve of BSA
      desorption could be reduced to the sum of two independent and simultaneous first
      order processes occurring at different rates. The desorption rate constant (k(f))
      for a faster-desorbing BSA (BSA(f)) was influenced by theta, especially above
      0.7. On the other hand, the rate constant (k(s)) for a slower-desorbing BSA
      (BSA(s)) was fairly constant irrespective of theta and approximately 25- to 100
      fold lower than k(f). The amount of BSA(f) estimated was proportional to theta,
      whereas that of BSA(s) reached a plateau value corresponding to 12.8% of
      saturation amount at theta above 0.42.

PMID- 16290792
TI  - Compaction of DNA by gemini surfactants: effects of surfactant architecture.
AB  - The interaction between bacteriophage T4 DNA and cationic gemini surfactants was
      studied by the use of fluorescence microscopy. Upon addition of surfactant, DNA
      undergoes a transition from random coil to globule, with an intermediate
      coexistence region. The state behavior of a DNA-gemini surfactant system was
      found to depend on spacer length, valency, head group size, and tail length. A
      series of alkanediyl-alpha,omega-bis-(dimethylalkylammonium bromide) surfactants
      with fixed tail length and variable spacer length s showed a minimum of
      compaction efficiency at s=6 due to the competition between entropy loss and
      enthalpy gain. This occurs at roughly the same spacer length at which the
      critical micellization concentration shows a maximal value (at s=5). In
      comparison with a single-tailed divalent surfactant (12-3-1) it was shown that
      the two-tailed equivalent (12-3-12) was more efficient in compacting DNA. A
      series of gemini surfactants based on cationic peptides with a alpha,omega
      diamino alkyl spacer showed similar behavior upon changing the spacer length.
      Additionally, two surfactants based on diastereomers of tartaric acid with
      hexadecanoic acid tails and alpha,omega-diaminopropanyl and spermidine head
      groups, respectively, showed effects of head group size that depended strongly on
      entropy effects. The dependence on valency of the head group is found to be
      similar to what is known for mono- and multivalent ions, the latter being more
      efficient per unit of charge.

PMID- 16290793
TI  - Shaping of gelling biopolymer drops in an elongation flow.
AB  - Shaping, defined as deformation in combination with gel formation of gelatine and
      kappa-carrageenan drops in an elongation flow, was studied. The focus was to
      investigate the possibility of shaping and fixating small drops in the diameter
      range 20 to 229 mum. In the shaping progress and the influence of experimental
      properties, the viscosity, temperature, and flow of the deforming fluid were
      examined on the final drop shape. In the experiments a hot emulsion of an aqueous
      biopolymer solution in silicone oil was injected into cold silicone oil where a
      deforming elongation flow field existed. After injection, a temperature decrease
      in the drops resulted in a gel formation of the biopolymer and a fixation of the
      deformed drop in the flow. The shape was measured and the effect on the drop
      aspect ratio was determined by image analysis. Over the total drop diameter
      range, kappa-carrageenan was more ellipsoid-shaped than gelatine, with a maximum
      aspect ratio of 6 compared to 4 for gelatine. For small drops, around 22 mum, it
      is possible to shape kappa-carrageenan, but for gelatine small drops tend to be
      unaffected. An increase in viscosity, temperature, and flow resulted in an
      increase in the final fixated shape of the drops. The differences in drop
      deformation between the biopolymers were explained by drop-viscosity/oil
      differences and differences in the kinetics of gel formation. The different gel
      formation kinetics resulted in a short, well-defined, shaping process for kappa
      carrageenan, while for gelatine the process was more complex, with both
      deformation and relaxation present at different stages.

PMID- 16290794
TI  - Biomembrane phospholipid-oxide surface interactions: crystal chemical and
      thermodynamic basis.
AB  - Quartz has the least favored surface among many oxides for bacterial attachment
      and for lipid bilayer or micelle interactions. Tetrahedrally coordinated
      crystalline silica polymorphs are membranolytic toward liposomes, lysosomes,
      erythrocytes, and macrophages. Amorphous silica, the octahedral silica polymorph,
      (stishovite), and oxides such as Al2O3, Fe2 O3, and TiO2 are less cytotoxic.
      Existing theories for membrane rupture that invoke interactions between oxide
      surfaces and cell membrane phospholipids (PLs) do not adequately explain these
      differences in membranolytic potential of the oxides. The author presents a
      crystal chemical, thermodynamic model for the initial interaction of oxide
      surfaces with the quaternary ammonium component of the PL's polar head group. The
      model includes solvation energy changes and electrostatic forces during
      adsorption, represented by the dielectric constant of the solid and the charge-to
      radius ratio of the adsorbing solute. The nature of oxide-solute interactions
      compared with oxide-water, solute-water, and water-water interactions determines
      the membranolytic activity of the oxide, where the solute is TMA+, the quaternary
      ammonium moeity. Significant membrane rupture, as on quartz, requires unfavorable
      adsorption entropy (DeltaS(ads,TMA+)<0) to maximize disruption of normal membrane
      structure and requires favorable Gibbs free energy of exchange between TMA+ and
      the ambient Na+ ions (DeltaG(exc,TMA+/Na+) = DeltaG(ads,TMA+)-DeltaG(ads,Na+)<0)
      to maximize the extent of membrane affected. For amorphous silica,
      DeltaS(ads,TMA+) >0, so disruption of structure is limited, even though
      G(exc,TMA+/Na+) is <0. Stishovite and other oxides have DeltaS(ads,TMA+) <0, but
      now DeltaG(exc,TMA+/Na+) is>0 at the acidic to circumneutral pHs of cellular and
      subcellular organelle fluids. The model predicts the correct sequence of
      membranolytic ability: quartz > or = amorphous SiO2 >Al2O3 >Fe2O3 >TiO2. The
      model thus explains the relatively poor adhesion of bacterial cells to quartz and
      the lack of quartz as a biomineral. It is proposed that one function of
      extracellular polymeric substances exuded by bacteria is to render mineral
      surfaces more hydrophilic.

PMID- 16290795
TI  - Effects of flow on measurements of interactions in colloidal suspensions.
AB  - A hydrodynamic mechanism of interactions of colloidal particles is considered.
      The mechanism is based on the assumption of tiny background flows in the
      experimental cells during measurements by Grier et al. Both trivial (shear flow)
      and nontrivial (force propagation through viscous fluid) effects are taken into
      account for two colloidal particles near a wall bounding the solvent. Expressions
      for the radial (attractive or repulsive) forces and the polar torques are
      obtained. Quantitative estimates of the flow needed to produce the observed
      strength of attractive force are given; other necessary conditions are also
      considered. The following conclusion is made: the mechanism suggested most likely
      is not responsible for the attractive interactions observed in the experiments of
      Grier et al.; however, it may be applicable in other experimental realizations
      and should be kept in mind while conducting colloidal measurements of high
      sensitivity. Several distinctive features of the interactions due to this
      mechanism are identified.

PMID- 16290796
TI  - Generalizations for the potential of mean force between two isolated colloidal
      particles from Monte Carlo simulations.
AB  - A substantial amount of experimental and numerical evidence has shown that the
      Derjaguin-Landau-Verwey-Overbeek theory is not suitable for describing those
      colloidal solutions that contain multivalent counterions. Toward improved
      understanding of such solutions, the authors report Monte Carlo calculations
      wherein, following Rouzina and Bloomfield, they postulate that, in the absence of
      van der Waals forces, the overall force between two isolated charged colloidal
      particles in electrolyte solutions is determined by a dimensionless parameter
      Gamma=z(2)l(B)/a, which measures the electrostatic repulsion between counterions
      adsorbed on the macroion surface, where z = counterion valence, l(B)=Bjerrum
      length, and a = average separation between counterions on the macroion surface
      calculated as if the macroion were fully neutralized. The authors find, first,
      that the maximum repulsion between like-charged macroions occurs at Gamma
      approximately 0.5 and, second, that onset of attraction occurs at Gamma
      approximately 1.8, essentially independent of the valence and concentration of
      the surrounding electrolyte. These observations might provide new understanding
      of interactions between electrostatic double layers and perhaps offer
      explanations for some electrostatic phenomena related to interactions between DNA
      molecules or proteins.

PMID- 16290797
TI  - Synthesis and pH-selective adsorption of latex particles onto
      photolithographically patterned silane layers.
AB  - Surface structures of charged latex particles on patterned surface layers were
      obtained by a colloidal self-assembly process. The laterally patterned silane
      layers were prepared on silica surfaces by vapor phase and solution deposition of
      silanes in combination with photolithography. The monodisperse latex particles
      used in the self-assembly experiments were synthesized by emulsion polymerization
      to yield poly-n-butylmethacrylate spheres (217 nm diameter) and poly-n
      butylacrylate microgels (155 nm). Both particle types possessed a high surface
      concentration of free carboxylic acid groups as quantified by polyelectrolyte
      titration under shear flow. Depending on the pH, the particles assembled onto the
      hydrophobic surface regions (pH 9) or onto the hydrophilic regions (pH 5).
      Highest selectivity and pattern quality was obtained with permanently positively
      charged silane layers (quaternary ammonium salts) onto which the negatively
      charged colloid particles adhered strongly by Coulomb interaction.

PMID- 16290798
TI  - Synthesis of uniform anatase TiO2 nanoparticles by gel-sol method. 1. Solution
      chemistry of Ti(OH)(4-n)+(n) complexes.
AB  - The mole fractions of hydroxo complexes of titanium(IV) ion in an aqueous
      solution with 0.10 mol dm(-3) NaClO4 at 25 degrees C have been determined as a
      function of pH by a newly developed analytical procedure based on UV
      spectrophotometry, using a metastable homogeneous solution of 1.25 x 10(-4) mol
      dm(-30 in total concentration of Ti(IV). Also, the total concentration of the
      hydroxo complexes in equilibrium with Ti(OH)4 solid, or the solubility of Ti(OH)4
      solid in an inhomogeneous system, has been obtained by ICP measurement for the
      solution phase. A combination of these data yielded the absolute concentration of
      each complex species in equilibrium with Ti(OH)4 solid. Finally, Ti(OH)+3 complex
      has been assigned to the precursor for the formation of anatase TiO2
      nanoparticles transformed from Ti(OH)4 gel from a comparison between the above
      equilibrium data and a kinetic study on the formation rate of the anatase TiO2
      particles in the gel-sol system.

PMID- 16290799
TI  - Synthesis of uniform anatase TiO2 nanoparticles by the gel-sol method 2.
      Adsorption of OH- Ions to Ti(OH)4 gel and TiO2 particles.
AB  - The pH value in the gel-sol system for the preparation of uniform anatase TiO2
      nanoparticles, as a decisive factor for controlling the size and shape of the
      final product, was found to be significantly changed during the formation process
      of the anatase TiO2 particles from a condensed Ti(OH)4 gel. The dramatic
      evolution of pH with the progress of the synthetic process has clearly been
      explained in terms of the adsorption and desorption of a hydroxide ion (OH-) ora
      proton (H+) on the solids transforming with time. The adsorption and desorption
      of OH- or H+ were enhanced by the presence of an inert electrolyte such as
      NaClO4, as explained by its shielding effect on the electrical interactions
      between the electrically charged precipitates and free OH- and H+ ions. The
      electrolyte also hampered the phase transformation of Ti(OH)4 precipitate to
      anatase TiO2. This effect of electrolytes was explained in terms of the inhibited
      nucleation of anatase TiO2 by enhanced adsorption of OH- ions toTiO2 embryos. The
      points of zero charge (PZC) of the amorphous Ti(OH)4 precipitate and the anatase
      TiO2 particles at 25 degrees C were obtained from the change in pH associated
      with the adsorption and desorption of OH- or H+, i.e., 4.6 for Ti(OH)4
      precipitate and 6.0 for anatase TiO2 in the presence of 0.1 mol dm(-3) NaClO4.
      The PZCof the Ti(OH)4 precipitate measured at 25 degrees C after additional aging
      at 100 degrees C for 30 min was shifted to 4.1, owing to the promoted adsorption
      of OH-.

PMID- 16290800
TI  - Diffusioosmosis and electroosmosis of electrolyte solutions in fibrous porous
      media.
AB  - The steady diffusioosmotic and electroosmotic flows of an electrolyte solution in
      the fibrous porous medium constructed by a homogeneous array of parallel charged
      circular cylinders are analyzed under conditions of small Peclet and Reynolds
      numbers. The imposed electrolyte concentration gradient or electric field is
      constant and can be oriented arbitrarily with respect to the axes of the
      cylinders. The thickness of the electric double layers surrounding the cylinders
      is assumed to be small relative to the radius of the cylinders and to the gap
      width between two neighboring cylinders, but the polarization effect of the
      diffuse ions in the double layers is incorporated. Through the use of a unit cell
      model, the appropriate equations of conservation of the electrochemical potential
      energies of ionic species and the fluid momentum are solved for each cell, in
      which a cylinder is envisaged to be surrounded by a coaxial shell of the fluid.
      Analytical expressions for the diffusioosmotic and electroosmotic velocities of
      the bulk electrolyte solution as functions of the porosity of the ordered array
      of cylinders are obtained in closed form for various cases. Comparisons of the
      results of the cell model with different conditions at the outer boundary of the
      cell are made. In the limit of maximum porosity, these results can be interpreted
      as the diffusiophoretic and electrophoretic velocities of an isolated circular
      cylinder caused by the imposed electrolyte concentration gradient or electric
      field.

PMID- 16290801
TI  - Dependence of phase behavior of some non-ionic surfactants at the air-water
      interface on micellization in the bulk.
AB  - The temperature-dependent surface phase behavior of two sparingly soluble
      surfactants, namely, ethylene glycol n-dodecyl ether (EGDE) and ethylene glycol n
      tetradecyl ether (EGTE), at the air-water interface was investigated by film
      balance and Brewster angle microscopy (BAM). A cusp point followed by a
      pronounced plateau region in the surface pressure-time (pi-t) adsorption
      isotherms of the amphiphiles measured by film balance indicates the first-order
      phase transition. Bright two-dimensional condensed phase domains in a dark
      background are observed by BAM just after the phase transition. In both cases the
      critical surface pressure necessary for the phase transition increases with
      increasing temperature. The domains are found to be circular up to 5 and 27
      degrees C for EGDE and EGTE, respectively, above which they show a fingering
      pattern. Condensed domains are observed up to 23 and 37 degrees C for EGDE and
      EGTE, respectively. The surface properties of the amphiphiles are found to be
      markedly affected by their tendency to aggregate in the bulk as micelles. The CMC
      values of both the amphiphiles show a maximum at a definite temperature, T(max),
      that corresponds well to their respective maximum temperatures of domain
      formation. An increase in temperature beyond T(max) results in an increasing
      trend for the formation of micelles. Consequently the system suffers from a
      shortage of two-dimensional surface concentration of the molecules to attain the
      surface pressure necessary for phase transition. With increasing temperature, the
      enthalpy, DeltaH(m) degrees , and entropy, DeltaS(m) degrees , of micellization
      change from negative to positive in both cases. An enthalpy-entropy compensation
      effect is found to hold for both the amphiphiles over the entire temperature
      range. The thermodynamic quantities reveal that the increase in temperature is
      favorable for micellization when the temperature exceeds the corresponding T(max)
      of the amphiphiles.

PMID- 16290802
TI  - Effect of capillary element aspect ratio on the dynamic imbibition within porous
      networks.
AB  - The Washburn equation is widely accepted for describing capillary imbibition. It
      has, however, been shown to be insufficient at very short times due partly to the
      lack of inertial terms. Bosanquet (C. H. Bosanquet, Philos. Mag. ser. 645, 525
      (1923)) applied an inertial term via momentum, Szekely et al. (J. Szekely, A. W.
      Neumann, and Y. K. Chang, J. Colloid Interface Sci.35, 273 (1971)) examined
      single capillaries based on a revised boundary-condition model, and Sorbie et al.
      (K. S. Sorbie, Y. Z. Wu, and S. R. McDougall, J. Colloid Interface Sci. 289
      (1995)) reviewed and applied Szekely's work to examine the effects of comparative
      imbibition into a parallel pore doublet. The study here extends the work of
      Sorbie et al. by applying the equation of Bosanquet to a three-dimensional
      network model, Pore-Cor. All authors agree that, with the inclusion of inertial
      terms at short times, smaller radius capillaries will initially fill faster than
      larger radius capillaries which disagrees with the Washburn equation. It is shown
      that the aspect ratio of a capillary, defined as its length divided by its
      radius, plays an important role, in combination with the capillary radii
      themselves, in determining the filling rate of individual elements. The
      distribution of this ratio associated with the capillary throat elements within a
      network structure is investigated. The result is that a preferred pathway of
      permeation is observed under supersource imbibition conditions in the case where
      a broad size distribution of capillary elements occurs within a network
      structure.

PMID- 16290803
TI  - Multilevel structure of sludge flocs.
AB  - In this work, the structure of two kaolin sludges and a waste activated sludge
      are investigated using both light-scattering and free-settling methods. Fractal
      dimensions estimated by the light-scattering and free-settling techniques (D(S)
      and D(F) respectively) differ significantly and support the hypothesis that
      naturally occurring aggregates possess a multilevel structure. A two-level floc
      structural model comprised of (i) a primary floc (of fractal dimension D(S))
      consisting of primary particles and (ii) a secondary floc (of fractal dimension
      D(F)) consisting of the microflocs is proposed to interpret the experimental
      findings. The structural changes of sludge flocs before and after cationic
      flocculation are interpreted using the proposed two-level model.

PMID- 16290804
TI  - Adsorption characteristics of bisphenol A onto carbonaceous materials produced
      from wood chips as organic waste.
AB  - Many organic by-products have been discharged by humans, and the development of
      technology for recycling organic by-products has attracted much interest. In this
      paper, the techniques for producing carbonaceous adsorbents from an organic by
      product and an application to remove endocrine disruptors are described. Wood
      chips as an organic by-product were carbonized at 873 to 1073 K. The iodine
      adsorption capacity of the obtained carbonaceous materials increased with
      increasing carbonization temperature. The amount of bisphenol A adsorbed on the
      carbonized materials produced from Sugi and Hinoki at a 1073 K carbonization
      temperature was higher than that of activated carbon. The Freundlich constant,
      1/N, of the carbonaceous materials produced from Sugi chips, Sugi sawdust, and
      Hinoki sawdust was similar to that of the activated carbon. This result indicated
      that the affinity between bisphenol A and the carbonaceous materials or the
      activated carbon was similar. Their Freundlich constant, K, was greater than that
      of the activated carbon. Hence, bisphenol A could be efficiently removed by the
      carbonaceous materials.

PMID- 16290805
TI  - Spreading of liquid drops over dry porous layers: complete wetting case.
AB  - Spreading of small liquid drops over thin dry porous layers is investigated from
      both theoretical and experimental points of view. Drop motion over a porous layer
      is caused by an interplay of two processes: (a) the spreading of the drop over
      already saturated parts of the porous layer, which results in an expanding of the
      drop base; (b) the imbibition of the liquid from the drop into the porous
      substrate, which results in a shrinkage of the drop base and an expanding of the
      wetted region inside the porous layer. As a result of these two competing
      processes, the radius of the drop goes through a maximum value over time. A
      system of two differential equations is derived to describe the evolution with
      time of radii of both the drop base and the wetted region inside the porous
      layer. This system includes two parameters: one accounts for the effective
      lubrication coefficient of the liquid over the wetted porous substrate and the
      other is a combination of permeability and effective capillary pressure inside
      the porous layer. Two additional experiments are used for an independent
      determination of these two parameters. The system of differential equations does
      not include any fitting parameter after these two parameters are determined.
      Experiments were carried out on the spreading of silicone oil drops over various
      dry microfiltration membranes (permeable in both normal and tangential
      directions). The time evolution of the radii of both the drop base and the wetted
      region inside the porous layer are monitored. All experimental data fell on two
      universal curves if appropriate scales are used with a plot of the dimensionless
      radii of the drop base and of the wetted region inside the porous layer on
      dimensionless time. The predicted theoretical relationships are two universal
      curves accounting quite satisfactorily for the experimental data. According to
      our theory prediction, (i) the dynamic contact angle dependence on the same
      dimensionless time as before should be a universal function and (ii) the dynamic
      contact angle should change rapidly over an initial short stage of spreading and
      should remain a constant value over the duration of the rest of the spreading
      process. The constancy of the contact angle on this stage has nothing to do with
      hysteresis of the contact angle: there is no hysteresis in our system. These
      conclusions again are in good agreement with our experimental observations.

PMID- 16290806
TI  - Bitumen-clay interactions in aqueous media studied by zeta potential distribution
      measurement.
AB  - A novel technique to investigate the interactions between bitumen and clays in an
      aqueous solution from the measurement of zeta potential distributions is
      described. For a single component suspension (i.e., clay or bitumen), a single
      modal zeta potential distribution was obtained under a given solution condition.
      In the case of a two-component (i.e., bitumen and clay) mixture system, the
      measured zeta potential distribution showed either one or two distribution peaks,
      depending on the chemical condition of the suspension and the type/amount of
      clays present. In the absence of added calcium ions, a mixture of bitumen
      emulsion and clay suspension exhibited two distinct zeta potential distribution
      peaks, corresponding to the peaks measured individually for the bitumen and
      clays, respectively. With the addition of 1 mM calcium ions, however, only one
      zeta potential distribution peak was obtained for the mixture of bitumen emulsion
      and montmorillonite clay suspension. Depending on the montmorillonite clay to
      bitumen ratio, the peak position in this case shifted toward the value for
      montmorillonite clay suspension alone. For kaolinite, the addition of 1 mM
      calcium ions did not cause a substantial change in the bimodal zeta potential
      distribution. The results suggest qualitatively a stronger interaction of bitumen
      with montmorillonite clay than with kaolinite clay, when calcium ions were
      present. The slime coating of montmorillonite clay on bitumen droplets in the
      presence of 1 mM calcium was validated. The conclusions obtained from this study
      further justified our mechanistic hypothesis for the observed depression of
      bitumen flotation by montmorillonite but not by kaolinite clay addition when
      calcium ions were added. This study demonstrated that zeta potential distribution
      measurement could be a powerful tool to study slime coating phenomena in a
      complex colloidal system.

PMID- 16290807
TI  - Effects of protonation of alkyldimethylamine oxides on the dissolution
      temperature in aqueous media.
AB  - The effects of protonation (ionization) of hexadecyldimethylamine oxides on the
      dissolution temperature in aqueous media were investigated by differential
      scanning calorimetry. Only one endothermic peak was reproducibly observed at all
      the degrees of ionization alpha examined that were assigned to the transition
      from the solid (the gel phase) to the solution containing micelles. The
      dissolution temperature versus alpha curves showed a maximum at alpha=0.5,
      strongly suggesting the formation of a stable complex of 1-to-1 composition of
      the nonionic and cationic species through the proposed hydrogen bond. From the
      shape of the dissolution curve as well as the composition analysis of the solid
      phase, the solid solution was found to be formed over all alpha values. Effects
      of alkylchain length on the dissolution temperature for a homologous series of
      octadecyl- (C18DAO), hexadecyl- (C16DAO), and tetradecyldimethylamine oxide
      (C14DAO) were also examined for alpha=0.5 and alpha=1. Both the transition
      temperature and the associated thermodynamic quantities DeltaH and DeltaS
      increased systematically with the chain length, but for alpha=0.5 smaller
      increases in DeltaH and DeltaS values with the chain length were observed
      [DeltaH/CH2 (kJ mol(-1))=7.2+/-0.2 and 2.2+/-0.5 for alpha=1 and alpha=0.5,
      respectively, and DeltaS/CH2 (J mol(-1) K(-1))=21.9+/-1.8 for alpha=1 and 4.6+/
      1.9 for alpha=0.5]. By annealing procedures, the metastable nature of the gel
      phase was demonstrated for the C16DAO (alpha=1) solid.

PMID- 16290808
TI  - Surface acid-base behaviors of Chinese loess.
AB  - Acid-base titration was applied to investigate the surface acid-base properties
      of a Chinese loess sample at different ionic strengths. The acidimetric
      supernatant was regarded as the system blank of titration to correct the
      influence of particle dissolution on the estimation of proton consumption. The
      titration behavior of the system blank could be described by the hydrolysis of
      Al3+ and Si(OH)4 in aqueous solution as well as the production of
      hydroxyaluminosilicates. The formation of Al-Si species on homogeneous surface
      sites by hydrous aluminum and silicic acid, released from solid substrate during
      the acidic titration, was considered in the model description of the back
      titration procedure. A surface reaction model was suggested as follows: >SOH<-
      >>SO(-)+H+, pK(a)(int)=3.48-3.98;>SOH+Al(3+)+H4SiO4<-->>SOAl(OSi(OH)3(+)+2H+,
      pK(SC)=3.48-4.04. Two simple surface complexation models accounted for the
      interfacial structure, i.e., the constant capacitance model (CCM) and the diffuse
      layer model (DLM), and gave a satisfactory description of the experimental data.
      Considering the effect of ionic strength on the electrostatic profile at the
      solid-aqueous interface, the DLM was appropriate at the low concentrations (0.01
      and 0.005 mol/L) of background electrolyte (NaNO3 in this study), while the CCM
      was preferable in the case of high ionic strength (0.1 mol/L).

PMID- 16290809
TI  - Frequency characteristics of amplitude and phase of oscillating bubble systems in
      a closed measuring cell.
AB  - The amplitude- and phase-frequency characteristics of oscillating bubble systems
      with a closed measuring cell are analyzed. The shape of the frequency
      characteristics is qualitatively different for bubbles smaller or larger than a
      hemisphere, respectively, and also for diluted and concentrated surfactant
      solutions. Moreover, the presence of a surfactant in the solution strongly
      influences the characteristic frequencies of the system. The experiments
      performed under ground and microgravity conditions show a good qualitative
      agreement with theoretically predicted amplitude- and phase-frequency
      characteristics and confirm the adequacy of the proposed theory. The comparison
      of high-frequency limits of the surface dilatational elasticity with the
      theoretical Gibbs elasticities calculated according to the respective adsorption
      isotherm shows good agreement for small surfactant concentrations. At higher
      concentrations large discrepancies are observed which can possibly be explained
      by the violation of the linearity condition for the surface layer.

PMID- 16290810
TI  - An unprecedented surface oxidation of polystyrene substrates by wet chemistry
      under basic conditions.
AB  - The surface of polystyrene substrates has been modified by wet chemistry
      consisting of a treatment with sodium hydroxide in a water-methanol solution at
      50 degrees C for 15 h, under air atmosphere. The resulting samples were analyzed
      by XPS and AFM. The surface functional groups (hydroxyl and carboxyl functions)
      were assayed by radiolabeling. All the results are consistent with a surface
      oxidation process.

PMID- 16290812
TI  - Scaling laws for geometry and macromolecules in solution: an interdisciplinary
      approach to statistical and thermal physics.
AB  - An interdisciplinary program, dealing with statistics within basic geometry, is
      presented and discussed across some modern physics. Its fundamentals are of
      general interest in physical chemistry, but specially suit investigating
      conformational statistics and universal scaling of polymer chains in solution. We
      pointed out an equivalence principle for shape and statistics that can
      straightforwardly link probability distributions to geometrical quantities at
      smaller length scales. The average polymer size is thus expected following
      analytically from the energy surface of its dimeric unit. This would finally
      suggest extending molecular mechanics to a geometrical setting that reaches the
      limit of vanishing scales.

PMID- 16290811
TI  - Study by 1H NMR of the concentration of monomer-units on interface polymer
      grafted on silica using magic angle spinning and relaxation techniques.
AB  - The segmental motion of poly(ethylene oxide) grafted on silica has been
      investigated by 1H and 13C magnetic resonance. The local monomer units
      concentration on an interface is evaluated. Two independent techniques, namely
      magnetic relaxation and magic angle spinning, are used and give a good agreement
      for the physical parameters describing the monomer units concentration on the
      surface. This behavior has been studied as a function of molecular weight of the
      chains, and each time also as a function of temperature.

PMID- 16290813
TI  - Adsorption from the organic phase in the octanoic acid-octylamine-silica system.
AB  - The adsorption of octanoic acid (Octac) and octylamine (Octam) onto silica from
      isooctane solutions has been studied, both from individual solutions of Octac and
      Octam and from mixtures of the two in isooctane. The results show that Octam has
      a slightly higher affinity than Octac for the silica surface. From mixtures of
      Octam and Octac, the adsorption behavior at excess Octam is found to be different
      from that at excess Octac. In the first case the results indicate some kind of
      multilayer formation, while in the latter case it appears as though the two
      adsorbates compete for the same adsorption sites on the silica surface. When the
      equilibrium concentrations of the two components approach the equimolar, however,
      the adsorption behavior is similar for the two cases.

PMID- 16290814
TI  - Concentration effects on adsorption of bacteriophage T4 lysozyme stability
      variants to silica.
AB  - The adsorption kinetics and dodeceyltrimethylammonium bromide-mediated elution of
      the wild type and two structural stability mutants of bacteriophage T4 lysozyme
      were recorded in situ, at silica surfaces. Experiments were performed at
      different solution concentrations, ranging from 0.01 to 1.0 mg/ml. Plateau values
      of adsorbed mass generally increased with increasing solution concentration, with
      the adsorbed layer being only partially eluted by buffer. Treatment with
      surfactant removed more of the adsorbed protein in each case, with the remaining
      adsorbed mass varying little with concentration. Comparison of the data to an
      adsorption mechanism allowing for three adsorbed states, distinguished by binding
      strength, showed that the fraction of adsorbed molecules present in the most
      tightly bound state (state 3) decreased as adsorption occurred from solutions of
      increasing concentration. However, the absolute amounts of state 3 molecules
      present in each case were less dependent on solution concentration. Adsorption of
      T4 lysozyme into state 3 is suggested to occur early in the adsorption process
      and continue until some critical surface concentration is reached. Beyond this
      critical value of adsorbed mass, adsorption is suggested to progress with
      adoption of more loosely bound states.

PMID- 16290817
TI  - A controlled trial of cognitive-behavior therapy combined with vestibular
      rehabilitation in the treatment of dizziness.
AB  - Dizziness is a common and often untreated symptom in the general population. The
      aim of this study was to investigate the effects of a combined cognitive
      behavioral/vestibular rehabilitation (VR) program, using a randomized control
      design. A total of 29 participants were randomized to treatment consisting of
      psychoeducation, vestibular exercises, relaxation and cognitive interventions, or
      to serve as waiting list controls. Measures of dizziness-related handicap,
      dizziness-provoking movements, and daily diary registrations of dizziness
      symptoms at pre- and post-treatment showed statistically significant improvements
      in many domains, which translated to moderate effect sizes. These findings
      provide preliminary support for the combination of Cognitive-behavioral therapy
      (CBT) and VR methods in the treatment of dizziness.

PMID- 16290816
TI  - Dysfunctional attitudes in seasonal affective disorder.
AB  - Research examining dysfunctional attitudes in Seasonal Affective Disorder (SAD)
      has produced contrasting results. The present study sought to resolve this
      contradiction by addressing some methodological problems of the previous studies.
      The study examined dysfunctional attitudes using the Dysfunctional Attitudes
      Scale (DAS) in individuals with SAD and never-depressed controls. The SAD group
      were tested both when depressed in the winter (Time 1) and during their remission
      period (Time 2). At Time 1 the SAD group displayed a relatively elevated DAS
      compared to controls and to their Time 2 scores. These data therefore provide
      potential support for a view that SAD is characterized by underlying
      dysfunctional attitudes.

PMID- 16290818
TI  - Effects of tetrabromobisphenol A on larval development and thyroid hormone
      regulated biomarkers of the amphibian Xenopus laevis.
AB  - Effects of tetrabromobisphenol A (TBBA) on thyroid hormone (TH)-dependent
      morphological development and on TH-regulated biomarkers were investigated using
      the amphibian Xenopus laevis. Tadpoles were exposed in the Xenopus metamorphosis
      assay to different TBBA concentrations ranging from 2.5 to 500 microg/L for 21
      days. Only the highest TBBA concentration inhibited larval development while the
      biomarker for negative feedback mechanism, TH receptor beta-mRNA, was not
      affected. Short-term exposures to TBBA, triiodothyronine (T3), and a combination
      of TBBA and T3 were performed to examine expression of TH-upregulated biomarkers.
      TBBA alone increased slightly the expression of TH receptor beta- and basic
      region leucin zipper transcription factor b/Zip-mRNA but inhibited their T3
      induced elevation in a dose-dependent manner. Despite the fact that TBBA seems to
      cause only mild effects during long-term treatment on larval development, short
      term exposure revealed indirect evidence that TBBA can function as a TH
      antagonist.

PMID- 16290820
TI  - Social inequality in perceived environmental exposures in relation to housing
      conditions in Germany.
AB  - In Germany the impact of socioeconomic factors on environmental exposures and
      adverse housing conditions has been rarely studied up to now. The aim of our
      study was to assess whether and, if yes, how perceived exposure to noise and air
      pollution is influenced by socioeconomic status in Germany. We used data from a
      large-scale population-based survey. In this survey, data on perceived exposure
      to noise and air pollution and on socioeconomic status and housing conditions
      were collected on an individual basis. The study population consisted of 7,275
      adults aged 17-98 years (40% women), each representing the head of one household.
      For the association between perceived environmental exposure and social factors
      confounder-adjusted odds ratios (OR) with 95% confidence intervals were
      calculated by binary or ordinal logistic regression. In bivariate analyses
      subjects with non-German nationality, East Germans, respondents with low income,
      those with lower educational and occupational status, and subjects living in
      adverse housing conditions were more likely to report being highly exposed. In
      multivariate analyses high perceived exposure to noise was associated with low
      household income (OR 1.52 [95% CI 1.13-2.05] lowest versus highest income group).
      Perceived air pollution exposure was also related to household income (1.67 [1.14
      2.44] lower middle versus highest income group). Further associated variables
      were need for renovation of the house, type of house, and type of neighborhood.
      This study shows that in Germany, as in other industrial countries, environmental
      exposures are distributed unequally and that especially economic differences play
      important roles.

PMID- 16290819
TI  - Population exposure to ultraviolet radiation in Finland 1920-1995: Exposure
      trends and a time-series analysis of exposure and cutaneous melanoma incidence.
AB  - Ultraviolet radiation (UVR) is the principal cause of cutaneous malignant
      melanoma (CMM). However, the relation between CMM and UVR exposure is not clear.
      We present the trends of population exposure to UVR and conduct a time-series
      analysis of the relation between UVR exposure and incidence of CMM. Data on CMM
      incidence were obtained from the Finnish Cancer Registry. Clothing coverage of
      the body was scored from archival photographs and the proportion of uncovered
      skin was used as a measure of solar exposure. Information on the number of sunny
      resort holidays, duration of annual holidays, and sunscreen sales were obtained
      from various sources. Exposed skin area doubled from 1920 to 1985. The average
      duration of annual holidays increased 30-fold. The number of sunny resort
      holidays and the sales of sunscreens increased rapidly from 1980. CMM was most
      strongly associated with solar exposure of 5-19 years earlier. There is a
      considerable decrease in clothing coverage during the 20th century. UVR exposure
      preceding CMM occurrence 4 years or less does not appear relevant, whereas the
      period 5-19 years prior to CMM occurrence might be the most relevant period.
      However, findings of ecological studies may not be applicable at the individual
      level.

PMID- 16290822
TI  - On hydrodynamics of drag and lift of the human arm.
AB  - The work presents results on drag and lift measurement conducted in a low speed
      wind tunnel on a replica of the entire human arm. The selected model positions
      were identical to those during purely rotational front crawl stroke in quasi
      static conditions. A computational fluid dynamics model using Fluent showed close
      correspondence with the experimental results and confirmed the suitability of low
      speed wind tunnel for the drag and lift measurement in quasi-static conditions.
      The obtained profiles of the hydrodynamic forces were similar to the dynamic data
      presented in an earlier study suggesting that shape drag is a major contributing
      factor in propulsive force generation. The aim of this study was to underline the
      importance of the entire arm analysis, the elbow angle and a newly defined angle
      of attack representing the angle of shoulder rotation. It was found that both the
      maximum value of the drag force at 160 degrees elbow flexion angle and the
      momentum generated by it exceed the respective magnitudes for the fully extended
      arm. The latter is underlined by a prolonged plateau of near maximum drag that
      was obtained at shoulder angle range of 50-140 degrees suggesting that optimal
      arm configuration in terms of propulsive force generation requires elbow flexion.
      Furthermore it was found that drag trend is not consistent with the widely
      assumed and used sinus wave profile. A gap in the existing experimental research
      was filled as for the first time the entire arm lift and drag was measured across
      the entire stroke range.

PMID- 16290821
TI  - Molecular cloning and sequence analysis of a cDNA encoding pituitary thyroid
      stimulating hormone beta-subunit of the Chinese soft-shell turtle Pelodiscus
      sinensis and regulation of its gene expression.
AB  - A cDNA encoding thyroid stimulating hormone beta-subunit (TSHbeta) was cloned
      from pituitary of the Chinese soft-shell turtle, Pelodiscus sinensis, and its
      regulation of mRNA expression was investigated for the first time in reptile. The
      Chinese soft-shell turtle TSHbeta cDNA was cloned from pituitary RNA by reverse
      transcription and polymerase chain reaction (RT-PCR), and rapid amplification
      cDNA end (RACE) methods. The Chinese soft-shell turtle TSHbeta cDNA consists of
      580-bp nucleotides, including 67-bp nucleotides of 5'-untranslated region (UTR),
      402-bp of the open reading frame, and 97-bp of 3'-UTR followed by a 14 poly (A)
      trait. It encodes a precursor protein molecule of 133 amino acids with a putative
      signal peptide of 19 amino acids and a putative mature protein of 114 amino
      acids. The number and position of 12 cysteine residues, presumably forming six
      disulfide bonds, one putative asparagine-linked glycosylation site, and six
      proline residues that are found at positions for changing the backbone direction
      of the protein have been conserved in the turtle as in other vertebrate groups.
      The deduced amino acid sequence of the Chinese soft-shell turtle TSHbeta mature
      protein shares identities of 82-83% with birds, 71-72% with mammals, 49-57% with
      amphibians, and 44-61% with fish. The Chinese soft-shell turtle pituitaries were
      incubated in vitro with synthetic TRH (TSH-releasing hormone), thyroxine and
      triiodothyronine at doses of 10(-10) and 10(-8)M. TRH stimulated, while thyroid
      hormones suppressed, TSHbeta mRNA levels in dose-related manner. The sequences of
      cDNA and its deduced peptide of TSHbeta as well as the regulation of its mRNA
      level were reported for the first time in reptile.

PMID- 16290823
TI  - Stress-induced accumulation of glycerol in the flesh fly, Sarcophaga bullata:
      evidence indicating anti-desiccant and cryoprotectant functions of this polyol
      and a role for the brain in coordinating the response.
AB  - Nondiapausing larvae of the flesh fly, Sarcophaga bullata, responded to several
      forms of short-term environmental stress (low temperature, anoxia and
      desiccation) by accumulating glycerol. Elevation of this polyol, regardless of
      the type of stress that induced accumulation, conferred cold resistance: larvae
      with high glycerol levels were 3-4 times more tolerant of a 2h exposure to -10
      degrees C than unstressed larvae. Protection against low temperature injury, as
      well as dehydration, was also attained by injection of exogenous glycerol into
      third instar larvae. This artificially induced cold hardiness was only temporary:
      when glycerol-injected larvae were exposed to -10 degrees C immediately after
      injection, survival was high, but none survived if they were injected and then
      held at 25 degrees C for 2 days before the -10 degrees C exposure. Larvae ligated
      behind the brain immediately after low temperature exposure failed to accumulate
      glycerol, but glycerol did accumulate in larvae ligated 6-24h after cold
      treatment, thus implying a critical role for the brain in initiating glycerol
      production. Interestingly, a much shorter exposure (2h) to low temperature was
      sufficient to reduce the maximum rate of water loss. Collectively, these
      observations suggest that multiple pathways may be exploited in response to
      stress: one pathway is most likely associated with rapid cold hardening (RCH)
      which generates immediate protection, and a second pathway remains activated for
      a longer period to enhance the initial protection afforded by glycerol.

PMID- 16290824
TI  - Transport of kaolinite colloids through quartz sand: influence of humic acid,
      Ca(2+), and trace metals.
AB  - To evaluate the risk of contaminant transport by mobile colloids, it seems
      essential to understand how colloids and associated pollutants behave during
      their migration through uncontaminated soil or groundwater. In this study, we
      investigated at pH 4 the influence of flow velocity, humic acid, solution Ca(2+)
      concentrations, and trace metals (Pb(2+), Cu(2+)) on the transport and deposition
      of kaolinite particles through a pure crystalline quartz sand as porous medium. A
      short-pulse chromatographic technique was used to measure colloid deposition.
      Adsorption of humic acid to the kaolinite increase its negative surface charge
      and then decrease colloid deposition. Experiments with different flow rates
      showed that humic-coated kaolinite colloid deposition followed a first-order
      kinetic rate law. The deposition rate coefficients of humic-coated kaolinite
      colloids increase with increasing Ca(2+) concentration in the suspension. The
      effect of trace metals on the mobility is studied by injecting two suspensions
      with different concentrations of Pb(2+) and Cu(2+). At very low cation
      concentration, the fraction of colloids retained is low and roughly independent
      of the nature of divalent cations. At high concentration, the deposition is
      higher and depends on the affinity of divalent cations toward humic-coated
      kaolinite colloids.

PMID- 16290825
TI  - Studies on the transition behavior of physical adsorption from the sub- to the
      supercritical region: experiments on silica gel.
AB  - Adsorption equilibria of nitrogen and methane on a mesoporous silica gel were
      measured over a temperature range from the sub- to the supercritical region.
      Determination of the compressibility factor shows a significant effect on the
      experimentally measured isotherms under conditions rho(g)/rho(c)>0.3. The
      transition of adsorption mechanisms in passing over the critical temperature was
      proven by the transformation of isotherms from type II to type I. The
      characteristic feature of subcritical adsorption was still observed at a
      temperature 8 K higher than the critical and the critical depletion phenomenon
      was clearly shown on such an isotherm. The limit quantities defined in different
      ways for the supercritical adsorption are in reasonable agreement, indicating the
      existence of an upper limit state of the supercritical adsorbate.

PMID- 16290826
TI  - Heterogeneous extended langmuir model with multiregion surfaces for adsorption of
      mixtures.
AB  - The multiregion or multisite adsorption theory is applied to the heterogeneous
      extended Langmuir (HEL) model for predicting adsorption from mixtures. A new
      model, multiregion HEL (MR-HEL), is derived. MR-HEL is thermodynamically
      consistent. It uses the same three parameters for each component of the mixture
      as in the HEL model. Examples, including eight binary and one ternary systems,
      show that both MR-HEL and HEL yield satisfactory results for relatively ideal
      systems with like components. For nonideal and highly nonideal mixtures, however,
      MR-HEL reduces the total average deviation for the predicted amount adsorbed for
      each component by more than 50% in comparison with the original HEL model. The
      improvement by MR-HEL is significant. Moreover, the new model predicts not only
      an azeotrope for binary system CO(2)+C(3)H(8) that shows strong nonideal behavior
      but also the correct azeotropic composition.

PMID- 16290827
TI  - Influence of organics on the structure of water adsorbed on activated carbons.
AB  - The influence of organics on the structure of water adsorbed on activated carbons
      was studied using adsorption of nitrogen, benzene, and water, and by (1)H NMR
      spectroscopy with freezing out of bulk water with the presence of benzene-d(6) or
      chloroform-d. It was found that interactions of water with the activated carbon
      surface depend on both structural characteristics (contributions of micro- and
      mesopores, pore size distributions) of adsorbents and chemical properties
      (changed by oxidation or reduction) of the adsorbents. Moreover, the interfacial
      behavior of water is affected by water-insoluble organics such as benzene and
      chloroform. Changes in the Gibbs free energy of water adsorbed on carbons exposed
      to air, water, chloroform-d, or benzene-d(6) are related to textural properties
      of adsorbents and the degree of their oxidation. Since chloroform-d and benzene
      d(6) are strongly adsorbed on activated carbons and immiscible with water they
      replace a significant portion of adsorbed water in micropores, on the walls of
      mesopores, and in the transport pores of carbons causing changes in the Gibbs
      free energy and other characteristics of water.

PMID- 16290828
TI  - Structure, dynamics, and optical properties of concentrated milk suspensions: an
      analogy to hard-sphere liquids.
AB  - A systematic study of the effects of volume fraction increment on the optical
      properties, the structure, and the dynamics of the casein micelles and fat
      droplets in milk was performed using diffusing wave spectroscopy. Four types of
      milk were investigated, NIDO full fat milk, fat-free milk, whey and fat-free
      milk, and finally lactose and fat-free milk. Independent measurements to
      calculate the dependence of the viscosity and the index of refraction of the milk
      serum and casein micelles as a function of the volume fraction were also
      performed. We compare the experimentally determined quantities photon transport
      mean free path (l*) and self-diffusion coefficient D(s) with the predictions from
      theoretical calculations using classical colloidal models such as a hard-sphere
      fluid. We demonstrate that all types of milk with and without fat content behave,
      structurally, like colloidal hard-sphere systems up to volume fractions well over
      45%. In the case of dynamic measurements, both lactose- and fat-free and whey-
      and fat-free milk behave also like hard-sphere systems whereas fat-free milk and
      fat-containing NIDO milk deviate slightly at volume fractions over 35%. Finally,
      a comparative measurement and theoretical calculation of the casein micelle's
      size was performed.

PMID- 16290829
TI  - Study of adsorption behavior of bilirubin on human-albumin monolayer using a
      quartz crystal microbalance.
AB  - The quartz crystal microbalance was employed to study the adsorption behavior of
      bilirubin on human-albumin layer, which was chemically bound to the self
      assembled monolayer of 4-aminothiophenol on the surface of a gold electrode of
      the crystal via glutaraldehyde. A long-time adsorption process of bilirubin that
      took place on a human-albumin-modified surface was observed, and the adsorption
      kinetic parameters were estimated from the in situ frequency measurements. The
      amount of adsorbed bilirubin increased with increasing of both hydrogen ions and
      bilirubin concentration and was larger than that estimated based on the
      conclusion that there are two affinity sites for bilirubin per albumin molecule.
      With the present method, the displacement of bilirubin from an albumin layer
      caused by aspirin was also examined. QCM measurement provides a facile method for
      in situ monitoring of the adsorption/desorption of bilirubin on proteins layers.

PMID- 16290830
TI  - Colloidal particles derived from a complex of phosphotungstic Acid and
      ethoxylated surfactants.
AB  - Stable, colloidal sols of submicron size were prepared by titration of aqueous
      solutions of alkylene oxide surfactants with phosphotungstic acid,
      H(3)PW(12)O(40) (PTA), followed by neutralization with ammonium or potassium
      hydroxide. The stoichiometry of the complex between phosphotungstic acid and the
      ethoxylated surfactant was determined by (1)H and (31)P NMR and was dependent
      upon the degree of ethoxylation. For example, in the ethoxylated octylphenol
      having 9-10 ethylene oxide units, Triton X-100, the mole ratio of surfactant to
      PTA was 4.5. In the ethoxylated octylphenol having 70 ethylene oxide units,
      Triton X-705, the mole ratio of surfactant to PTA was 1. Prior to nucleation of
      particles, phosphotungstic acid forms an apparent yellow charge transfer complex
      with ethoxylated alkylphenol surfactants, typified by Triton X-405. This complex
      is characterized by an absorption spectrum that is the sum of the spectra of
      Triton X-405 and PTA with a very weak shoulder at 400-500 nm. Particles were
      nearly monodisperse and their size was dependent on the nonionic surfactant
      employed, the heteropolyacid, and the rate of addition of heteropolyacid
      solution.

PMID- 16290831
TI  - Preparation of Gd(2)O(3) : Eu(3+) and Gd(2)O(2)S : Eu(3+) phosphor fine particles
      using an emulsion liquid membrane system.
AB  - Size- (submicrometer-sized) and morphology- (spherical) controlled composite Gd
      Eu oxalate particles were prepared in an emulsion liquid membrane (water-in-oil
      in-water emulsion) system. The oxalate particles thus prepared were calcined in
      air to obtain Gd(2)O(3) : Eu(3+) phosphor particles and in sulfur atmosphere to
      obtain Gd(2)O(2)S : Eu(3+) phosphor particles. These submicrometer-sized
      spherical phosphor particles showed photoluminescence properties with emission
      peak at 614 nm for Gd(2)O(3) : Eu(3+) and 628 nm for Gd(2)O(2)S : Eu(3+).

PMID- 16290832
TI  - Stability of nanodispersions: a model for kinetics of aggregation of
      nanoparticles.
AB  - In the course of aggregation of very small colloid particles (nanoparticles) the
      overlap of the diffuse layers is practically complete, so that one cannot apply
      the common DLVO theory. Since nanopoarticles are small compared to the extent of
      the diffuse layer, the process is considered in the same way as for two
      interacting ions. Therefore, the Bronsted concept based on the Transition State
      Theory was applied. The charge of interacting nanoparticles was calculated by
      means of the Surface Complexation Model and decrease of effective charge of
      particles was also taken into account. Numerical simulations were performed using
      the parameters for hematite and rutile colloid systems. The effect of pH and
      electrolyte concentration on the stability coefficient of nanosystems was found
      to be more pronounced but similar to that for regular colloidal systems. The
      effect markedly depends on the nature of the solid which is characterized by
      equilibrium constants of surface reactions responsible for surface charge, i.e.,
      by the point of zero charge, while the specificity of counterions is described by
      their association affinity, i.e., by surface association equilibrium constants.
      The most pronounced is the particle size effect. It was shown that extremely
      small particles cannot be stabilized by an electrostatic repulsion barrier.
      Additionally, at the same mass concentration, nanoparticles aggregate more
      rapidly than ordinary colloidal particles due to thier higher number
      concentration.

PMID- 16290833
TI  - The pH-dependent surface charging and the points of zero charge.
AB  - The recently published points of zero charge of metal oxides and related
      materials are compiled to update the previous compilation. The purity of
      materials is the most important factor responsible for discrepancies in the
      literature data. In contrast to the success of new spectroscopic methods in the
      studies of specific adsorption, the progress in studies of primary surface
      charging of oxides over recent years is less spectacular.

PMID- 16290834
TI  - Dielectric relaxation on the intermediate layer in a bipolar membrane under the
      water splitting phenomenon. I. Shift of the dielectric properties by means of
      time-dependent impedance measurements.
AB  - In this study, we examined the dielectric properties of an intermediate layer in
      a bipolar membrane, which is composed of a negatively charged layer and a
      positively charged layer joined in series. As a result of the time-dependent
      impedance measurements of charged membranes, the negative increment in electric
      conductivity and the positive increment in electric capacity were observed only
      in the case of a bipolar membrane under the application of reverse-biased
      voltages, which were quite different from the behavior of both monopolar
      membranes and of a bipolar membrane under forward-biased voltages. Further, the
      observed shifts showed a nearly constant value against the reverse-biased
      voltage. It is concluded that these characteristics coincide with the process of
      ion exclusion in the intermediate layer and are attributed to the water splitting
      mechanism.

PMID- 16290835
TI  - Dielectric relaxation on the intermediate layer in a bipolar membrane under the
      water splitting phenomenon. II. Double dielectric relaxation and identification
      of phase parameters.
AB  - In this study, we investigated the impedance spectra of bipolar membranes. Under
      the application of a reverse-biased voltage, the spectra showed a double
      dielectric relaxation profile due to the heterogeneous structure and it was
      analyzed in accordance with the three-layered dielectric model. It is defined
      that one of the compositions of the heterogeneous structure is situated at the
      membrane interface region between the negatively and the positively charged
      membrane with a thickness of less than several micrometers, which has an
      extraordinarily large electric capacity with a magnitude of sub-microfarads. It
      is concluded that this layer is identified with the intermediate layer in which
      the water splitting phenomenon occurs on the bipolar membrane.

PMID- 16290836
TI  - Some problems of interface chemical mechanics.
AB  - On the basis of quasiton theory an expression was obtained for the potential of
      interpartical attractive macroforces in a curved interface, being between liquid
      and gas, for a centrally symmetric case when thickness the DeltaL of the area
      under study is commensurable with the radius of curvature r(s) of a bubble or a
      drop. Expressions were also obtained for normal and tangential components of a
      stress tensor in the interface; using variational principles, it is shown that
      density profiles in the interface cannot be equilibrium, and there is a
      probability that the surface tension for the fine bubble or drop may be even
      negative.

PMID- 16290837
TI  - Optical observation of gas bridging between hydrophobic surfaces in water.
AB  - The very strong and long-ranged interaction force between hydrophobic surfaces in
      water has been a debated issue for a long time. Recent studies suggest that the
      long-range attraction is attributable to the bridging of nanoscopic bubbles
      attached on the surfaces. However, it is still unclear at present whether such a
      bridging is able to exit stably or not. To clarify the existence of the gas
      bridge, we conducted the optical observation and the force measurement between
      the hydrophobic glass particle and plate in water simultaneously, using a
      combined apparatus of an atomic force microscope and an optical inverted
      microscope. It is found that (i) the image of the dark ring of ca. 1 mum in
      diameter appears in the region where the existence of the bridge is confirmed by
      force curves, but disappears when the separation between surfaces becomes shorter
      than the low limit of the wavelength of visible light, and (ii) the sudden
      disappearance of the image coincides well with the breakage of the bridge
      estimated from the separating force curve. The results obtained here are
      consistent with the above-mentioned mechanism for the long-range attraction
      between hydrophobic surfaces in water.

PMID- 16290838
TI  - Direct measurement of depletion and structural forces in polydisperse, charged
      systems.
AB  - The effect of polydispersity in macromolecule size or surface potential on the
      depletion interaction between a spherical silica particle and a silica flat in
      solutions containing two different types of nonadsorbing charged spherical
      macromolecules was studied with an atomic force microscope (AFM). The
      macromolecules used here were negatively charged nanospheres of either
      polystyrene or silica. To investigate the effect of size polydispersity,
      experiments were performed under the condition of either constant macromolecule
      number density or constant volume fraction as the relative proportions of smaller
      and larger polystyrene nanospheres in the suspension were varied. Similarly, for
      the experiments with surface potential polydispersity, the suspensions contained
      varying fractions of more highly charged (polystyrene) and less highly charged
      (Ludox silica) nanospheres at constant number density. The experimental results
      were compared to the predictions of the modified force-balance model of Piech and
      Walz and semiquantitative agreement was found. In particular, the maximum
      attraction and repulsion observed in the measured force profiles were found to
      agree with the predicted trends as the makeup of the macromolecules was varied.
      The trend in the maximum attraction was also consistent with predictions made
      using a simple "scaling" analysis derived using the equation for hard-sphere
      interactions.

PMID- 16290839
TI  - Determination of intrinsic bacterial surface acidity constants using a donnan
      shell model and a continuous pK(a) distribution method.
AB  - Intrinsic acidity constants (pK(a)(int)) for Bacillus subtilis (Gram+) and
      Escherichia coli (Gram-) cells were calculated from potentiometric titration data
      at different salt concentrations. Master curves were generated by replotting
      charge excess data as a function of pH(S) (pH at the location of surface reactive
      sites) where pH(S) was determined as a function of Donnan potential, Psi(DON).
      This potential decreased in magnitude with increasing ionic strength, from 
      48.5+/-0.2 to -3.5+/-0.0 mV for B. subtilis and -47.9+/-0.3 to -3.5+/-0.0 mV for
      E. coli at 0.01 and 0.5 M K(+), respectively, indicating an efficient surface
      charge neutralization by counterions. A fully optimized continuous (FOCUS) pK(a)
      distribution method revealed four binding sites on B. subtilis and E. coli
      surfaces from the master curves with pK(a)(int) values of 3.59+/-0.38, 4.33+/
      0.57, 5.94+/-0.66, and 8.64+/-0.57 for B. subtilis and 3.73+/-0.44, 4.85+/-0.71,
      6.56+/-0.64, and 8.79+/-0.62 for E. coli. These were assigned to functional
      groups according to reported pK(a) ranges of 2.0-6.0 (carboxylic acid), 3.2-3.5
      (phosphodiesters), 5.6-7.2 (phosphoric acid), and 9.0-11.0 (amine groups).
      Average points of zero salt effect (pH(pzse)) for B. subtilis experiments were
      6.63+/-0.21 and 6.42+/-0.08 as a function of pH(bulk) and pH(S), respectively.
      Under the same criteria, E. coli calculations yielded 5.73+/-0.23 and 5.45+/
      0.05. An understanding of metal and proton reactivity on bacterial cell surfaces
      can be addressed quantitatively through the use of electrostatic and chemical
      equilibrium modeling techniques proposed in this study. The results are
      consistent with those of electrical force microscopy studies used to document the
      intrinsic electrochemical heterogeneity of bacterial cell surfaces.

PMID- 16290840
TI  - Aggregation processes and formation of silico-calco-alkaline gels under high
      ionic strength.
AB  - This paper presents a systematic in situ study of the process of formation of
      silico-calco-alkaline gels starting from a liquid colloidal solution containing
      different alkaline ions and different calcium concentration until the final gel
      state. The combined use of X-ray and neutron small-angle scattering (SAS) and
      dynamical rheometry techniques lead to a consistent description of the structure
      of the aggregates and of the mechanisms of aggregation involved in gel formation.
      SAS results indicate that the aggregates are fractal objects, their structure
      strongly depending on calcium ion concentration. The differences in gelation
      kinetics for systems containing different alkaline ions were attributed to the
      effects of repulsive forces acting on the external surfaces of the fractal
      aggregates. The high ionic strength of the studied sols induces a non-classical
      dependence of these forces on the counter ion size.

PMID- 16290841
TI  - Flocculation behavior of asphaltenes in solvent/nonsolvent systems.
AB  - Diffusion coefficients of asphaltenes dissolved in two aromatic solvents, toluene
      d(8) or ethylbenzene-d(10), were measured with the pulsed-field gradient spin
      echo nuclear magnetic resonance (PFG-SE NMR) technique upon addition of
      flocculant (pentane-d(12) or heptane-d(16)). It was observed that the change in
      the diffusion coefficients, as a function of amount of added flocculant, was
      small in the concentration interval studied (up to 30 wt% alkane). Complementary
      kinetic flocculation studies were made at alkane additions above 55 wt%. The
      initial change in turbidity upon the addition of alkane was measured with an UV
      VIS spectrophotometer. The obtained stability ratio, W, showed that asphaltenes
      were least stable in the ethylbenzene-pentane system and most stable in the
      toluene-heptane system. These findings were in agreement with the PFG-SE NMR.
      When combining the results from the two different techniques it appeared as if
      there was a dramatic increase in flocculation above a certain "threshold
      concentration" of added alkane. Furthermore, the flocculation appeared to be
      reaction controlled until as much as 63 wt% of n-pentane or, alternatively, 68
      wt% of n-heptane had been added to the systems, after which the flocculation
      became primarily diffusion controlled. Finally, careful relaxation measurements
      showed that the asphaltenes displayed two distinctly different transverse (T(2))
      relaxation times (most probably averages), one at 0.6 ms and the other at 7 ms.

PMID- 16290842
TI  - Magnetization evolution in network models of porous rock under conditions of
      drainage and imbibition.
AB  - Surface-enhanced relaxation of nuclear magnetization in fully and partially
      saturated water-wet porous media is studied using a pore network simulator. The
      simulator is based on a description of the pore space in terms of a regular cubic
      lattice of pores and throats following respective size distributions. The latter
      are obtained from geometric characterization of 3D stochastic replicas of real
      porous rock samples. Concepts of percolation theory are used to simulate the pore
      scale distribution of a strongly wetting phase under conditions of quasistatic
      drainage by or imbibition against a nonwetting phase. The results of these
      simulations compare favorably with experimental mercury intrusion/retraction
      curves. The equations governing magnetization evolution in a connected pore
      system are then solved by matrix diagonalization for different values of wetting
      phase saturation along the primary drainage and secondary imbibition paths.
      Analysis of the corresponding spectra of decay rates provides new insights
      regarding the influence of pore structure (pore and throat size distributions,
      spatial correlation), surface relaxation strength, and fluid distribution on
      diffusive coupling between pores. For pore and throat size distributions and
      surface relaxation strength representative of sandstones, diffusive coupling is
      quite important, especially under conditions of partial saturation. Remarkably,
      simulations show that correlated heterogeneity is the main reason pores appear
      poorly coupled with respect to NMR relaxation-an assumption underlying the
      correspondence between pore size and relaxation time distributions. Finally, for
      a given value of wetting-phase saturation, the history of saturation change
      (drainage or imbibition) is shown to have a profound effect on the spectrum of
      decay rates.

PMID- 16290844
TI  - Covalent grafting of ethylene glycol and glycerol into brucite.
AB  - Layered brucite was synthesized at room temperature and, after characterization,
      was reacted in a closed flask with either ethylene glycol or glycerol. Powder X
      ray diffraction patterns have shown that new compounds with interlayer expansions
      were obtained. New bands attributed to grafting of ethylene glycol and glycerol
      into the interlayer surface of brucite were detected by FTIR. XPS spectroscopy
      and thermal analyses (TG/DSC) have shown that nearly all of the hydroxide groups
      of the layers were replaced by either ethylene glycol or glycerol through Mg-O-C
      bonds.

PMID- 16290843
TI  - Donnan equilibrium of ionic drugs in pH-dependent fixed charge membranes:
      theoretical modeling.
AB  - We have studied theoretically the partition equilibrium of a cationic drug
      between an electrolyte solution and a membrane with pH-dependent fixed charges
      using an extended Donnan formalism. The aqueous solution within the fixed charge
      membrane is assumed to be in equilibrium with an external aqueous solution
      containing six ionic species: the cationic drug (DH(+)), the salt cations (Na(+)
      and Ca(2+)), the salt anion (Cl(-)), and the hydrogen and hydroxide ions. In
      addition to these mobile species, the membrane solution may also contain four
      fixed species attached to the membrane chains: strongly acid sulfonic groups
      (SO(3)(-)), weakly acid carboxylic groups in dissociated (COO(-)) and neutral
      (COOH) forms, and positively charged groups (COO...Ca(+)) resulting from Ca(2+)
      binding to dissociated weakly acid groups. The ionization state of the weak
      electrolyte groups attached to the membrane chains is analyzed as a function of
      the local pH, salt concentration, and drug concentration in the membrane
      solution, and particular attention is paid to the effects of the Ca(2+) binding
      to the negatively charged membrane fixed groups. The lipophilicity of the drug is
      simulated by the chemical partition coefficient between the membrane and external
      solutions giving the tendency of the drug to enter the membrane solution due to
      hydrophobic interactions. Comparison of the theoretical results with available
      experimental data allows us to explain qualitatively the effects that the pH,
      salt concentration, drug concentration, membrane fixed charge concentration, and
      Ca(2+) binding exert on the ionic drug equilibrium. The role of the interfacial
      (Donnan) electric potential difference between the membrane and the external
      solutions on this ionic drug equilibrium is emphasized throughout the paper.

PMID- 16290845
TI  - Variability of dissolution rates at constant undersaturation.
AB  - Dissolution processes play an important role in marble weathering. Investigation
      of the dissolution kinetics of powdered Pentelic marble, a calcitic natural
      stone, showed that the rates measured at constant undersaturation decreased with
      time. It was found that the rate of dissolution decreased sharply to about 50% of
      the initial value before 5% of the initially suspended powder was dissolved. Past
      a dissolution extent corresponding to 25% with respect to the suspended solid,
      the rates of dissolution at the same constant undersaturation reached a stable
      value corresponding to 20-25% of the initial rate measured. The reduction in the
      rates of dissolution up to 25% of mass loss was in agreement with the reduction
      in the total surface area exposed to the solution, suggesting a dependence of the
      rate on the number of active sites on the surface of the dissolving material. The
      decrease in the dissolution rates did not depend on the undersaturation of the
      solution or on the physical characteristics of the particles such as specific
      surface area, porosity, and particle size distribution. Equal mass losses, with
      respect to the initially suspended solid, of different samples exhibited the same
      relative decrease in rate regardless of the conditions of the aqueous solutions.

PMID- 16290846
TI  - A comparative study of surfactant adsorption on model surfaces using the quartz
      crystal microbalance and the ellipsometer.
AB  - The nature of hexaethylene glycol mono-n-tetradecyl ether (C(14)EO(6)) layers
      adsorbed onto different model surfaces was systematically investigated by means
      of QCM-D (quartz crystal microbalance-dissipation) and ellipsometry. The amount
      of non-ionic surfactant adsorbed is determined both at hydrophilic and
      hydrophobic surfaces. In particular, the substrates employed were hydrophilic
      silica, hydrophobized silica (using dimethyldichlorosilane), and hydrophobized
      gold surfaces (using 10-thiodecane and 16-thiohexadecane). It was shown that the
      frequency shift obtained from the QCM-D experiments results in an overestimation
      of the adsorbed mass. This is attributed to two different effects, viz. water
      that is coupled to the adsorbed layer due to hydration of the polar region of the
      surfactant and second water that for other reasons is trapped within the adsorbed
      layer. Furthermore, from the ellipsometry data the adsorbed layer thickness is
      determined. By combining the thickness information and the dissipation parameter
      (obtained from the QCM-D experiments), we note that the dissipation parameter is
      insufficient in describing the viscoelastic character of thin surfactant films.

PMID- 16290847
TI  - Dynamic wetting by liquids of different viscosity.
AB  - The velocity-dependence of the dynamic contact angle is studied experimentally
      for a series of water-glycerol solutions having viscosities ranging from 1.5 to
      672 mPa s. The results are interpreted through a theory of dynamic wetting as an
      interface disappearance-formation process, with the goal to analyse the dominant
      microscopic mechanism by which the interface formation occurs. As is shown, an
      assumption that this mechanism is diffusive in nature allows one to adequately
      describe the whole set of experimental data. Some estimates for the
      phenomenological parameters of the model are obtained.

PMID- 16290848
TI  - Thermodynamic analysis of surface formation of {1,4-dioxane + 1-alkanol}
      mixtures.
AB  - Surface tensions (sigma) for {1,4-dioxane + methanol, ethanol, or 1-propanol} at
      the temperature 298.15 K and normal atmospheric pressure have been determined as
      a function of mole fractions. The experimental results have been analyzed using
      the ideal and Langmuir models and in the light of the well-documented bulk
      properties of these systems, which reflect hydrogen bonding between the alcohol
      and 1,4-dioxane molecules. For {1,4-dioxane + ethanol} surface tensions were also
      measured at other temperatures between 288.15 and 308.15 K, and these data were
      used to calculate the surface entropy and enthalpy per unit area.

PMID- 16290849
TI  - Local corrosion of magnesia-chrome refractories driven by Marangoni convection at
      the slag-metal interface.
AB  - The local corrosion of magnesia-chrome refractories containing MgO-Al(2)O(3)
      spinel has been investigated near the slag-metal interface by immersion tests.
      The local corrosion extent near the slag-metal interface was found to decrease
      with the increase of FeO, MgO, and Al(2)O(3) contents in the slag. The local
      corrosion depths in the diagonal direction on the cross sections of the square
      prism specimens were always 2 times those in the normal direction of the lateral
      faces, and the cross sections maintained their initial square shape during whole
      the corrosion duration. The local corrosion is reckoned to be driven by the
      Marangori convection, which accelerated the mass transfer of the components
      dissolved from the refractories.

PMID- 16290851
TI  - Electrorheological toners for electrophotography.
AB  - The electrorheological (ER) behavior of pigment suspensions dispersed in a
      nonaqueous solvent was examined for their application as liquid toners for
      electrophotography. In electric fields, particles can align into chains along the
      field vector by dielectric polarization forces and the suspensions undergo a
      rapid transition from Newtonian fluids to Bingham bodies. However, the migration
      and deposition of particles can take place by the electrophoretic effect, because
      charge control agents are added to liquid toners for fast development. The
      combined effects of dielectric polarization forces, electrophoretic forces, and
      hydrodynamic forces make rheological behavior very complicated. To simulate the
      ER behavior of liquid toners in reprographic processes, viscosity measurements
      were carried out in electrodes with a honeycomb pattern. Nonuniform electric
      fields enhance the dipole-dipole interactions between particles and give rise to
      a striking ER effect. Based on measurements in honeycomb pattern electrodes, new
      ER toners were developed which can reproduce images with high quality.

PMID- 16290850
TI  - Surface activity and emulsification properties of hydrophobically modified
      dextrans.
AB  - Neutral polymeric surfactants were synthesized by covalent attachment of
      hydrophobic groups (aromatic rings) onto a polysaccharide backbone (dextran). By
      changing the conditions of the modification reaction, the number of grafted
      hydrophobic groups per 100 glucopyranose units (substitution ratio) was varied
      between 7 and 22. In aqueous solution, these polymers behaved like classical
      associative polymers as demonstrated by viscometric measurements. The associative
      behavior was more pronounced when the substitution ratio increased. The surface
      active properties of the modified dextrans were evidenced by surface tension
      (air/water) and interfacial tension (dodecane/water) measurements. In each case
      the surface or interfacial tension leveled down above a critical polymer
      concentration, which was attributed to the formation of a dense polymer layer at
      the liquid-air or liquid-liquid interface. Dodecane-in-water emulsions were
      prepared using the polymeric surfactants as stabilizers, with oil volume
      fractions ranging between 5 and 20%. The oil droplet size (measured by dynamic
      light scattering) was correlated to the amount of polymer in the aqueous phase
      and to the volume of emulsified oil. The thickness of the adsorbed polymer layer
      was estimated thanks to zeta potential measurements coupled with size
      measurements. This thickness increased with the amount of polymer available for
      adsorption at the interface. The dextran-based surfactants were also applied to
      emulsion polymerization of styrene and stable polystyrene particles were obtained
      with a permanent adsorbed dextran layer at their surface. The comparison with the
      use of an unmodified dextran indicated that the polymeric surfactants were
      densely packed at the surface of the particles. The colloidal stability of the
      suspensions of polystyrene particles as well as their protection against protein
      adsorption (bovine serum albumin, BSA, used as a test protein) were also
      examined.

PMID- 16290852
TI  - Complexation between poly(maleic acid/octyl vinyl ether) and poly(vinyl
      caprolactam) in aqueous solution and at the alumina/water interface.
AB  - Solution and interfacial properties of binary polymer mixtures of poly(maleic
      acid/octyl vinyl ether) (PMAOVE) and poly(vinyl caprolactam) (PVCAP) have been
      studied for the alumina/water system. To test the hydrophobic effect, mixtures of
      poly(maleic acid/methyl vinyl ether) (PMAMVE) and PVCAP are also investigated and
      compared to the behavior of PMAOVE/PVCAP. At low pH, both polymer mixtures become
      turbid upon mixing. The turbidity increases at low mixing ratios of PVCAP to the
      vinyl ether component, reaches a maximum, and then decreases at higher mixing
      ratios. Upon shifting the pH to the alkaline range, i.e., pH 7.5 and above, the
      turbid solution becomes clear for both the polymer mixtures. Cloud point
      measurements indicate the absence of complexation of PVCAP with PMAMVE under the
      alkaline conditions, but strong interaction with PMAOVE. This is attributed to
      the different forces involved in the complexation among the polymers: H bonding
      for PVCAP/PMAMVE and both H bonding and hydrophobic effects for PVCAP/PMAOVE. At
      the alumina/water interface, the normally nonadsorbing PVCAP is triggered to
      adsorb by PMAOVE, attributed to the hydrophobic complexation between the two.
      However, the adsorption of PVCAP shows a maximum as a function of the
      concentration of PMAOVE. At concentrations of PMAOVE above the onset of its own
      plateau adsorption, the amount of PVCAP triggered to adsorb is reduced possibly
      due to the polymer complex formation in solution.

PMID- 16290853
TI  - Effects of micellar charge density on the coefficient of the Corrin-Harkins
      relation.
AB  - Effects of the micelle composition (ionic species fraction alpha(M)) on the
      coefficient of the Corrin-Harkins relation (k(CH)) of ionic/nonionic mixed
      micelles were examined in the case of dodecyldimethylamine oxide. Long alkyl
      chain amine oxides exist either in the nonionic or the cationic (protonated form)
      species depending on the pH of solutions and hence the control of the micelle
      composition near the critical micelle concentration (cmc) is possible by
      adjusting the pH of the solutions. On the basis of the cmc data from the surface
      tension measurements and the hydrogen ion titration curves, we evaluated the
      k(CH) values as a function of the micelle composition alpha(M) for the first
      time. The obtained k(CH) values were compared with the degree of the counterion
      binding, theta, in the solutions without added salt. The k(CH) values increased
      with alpha(M), and were approximately identical with theta for alpha(M)>0.4. In
      the range alpha(M)<0.4, it is likely that theta is greater than k(CH). An
      empirical relation proposed by D. G. Hall et al. ("Mixed Surfactant Systems," Am.
      Chem. Soc., Washington, D.C. 1992) on the relation between theta and the micelle
      composition was also compared with these experimental results. Experimental
      values, k(CH) and theta, followed the empirical relation for alpha(M)>0.4;
      however, both k(CH) and theta increased steeply in the range alpha(M) 0.25-0.3.

PMID- 16290855
TI  - Interaction of indigo carmine dye with chitosan evaluated by adsorption and
      thermochemical data.
AB  - Chitosan can use its protonated amine groups to adsorb strongly anionic species
      from diluted solutions. In this work, adsorption and thermochemical data on the
      interaction of the dye indigo carmine with chitosan in aqueous medium were found,
      in order to obtain new adsorption data on this relatively unexplored chitosan
      field. The studies were carried out by the batch method from 35 to 50 degrees C.
      The adsorption results were well fitted to both Langmuir and Freundlich
      adsorption models. The increase in the temperature decreased the adsorption of
      the dye. The enthalpy of interaction, when a monolayer of the dye was formed on
      the chitosan surface, delta(int)H, of -23.2 kJ mol(-1) was encountered for all
      temperature ranges studied. The spontaneity of the interaction is indicated by
      the delta(int)G values from -9.1 to -8.2 kJ mol(-1). Other thermodynamic
      quantities were also calculated and are discussed.

PMID- 16290856
TI  - Modeling of phase equilibrium and vapor adsorption on carbon black based on a
      combination of a lattice theory and equation of state.
AB  - A thermodynamic approach is developed in this paper to describe the behavior of a
      subcritical fluid in the neighborhood of vapor-liquid interface and close to a
      graphite surface. The fluid is modeled as a system of parallel molecular layers.
      The Helmholtz free energy of the fluid is expressed as the sum of the intrinsic
      Helmholtz free energies of separate layers and the potential energy of their
      mutual interactions calculated by the 10-4 potential. This Helmholtz free energy
      is described by an equation of state (such as the Bender or Peng-Robinson
      equation), which allows us a convenient means to obtain the intrinsic Helmholtz
      free energy of each molecular layer as a function of its two-dimensional density.
      All molecular layers of the bulk fluid are in mechanical equilibrium
      corresponding to the minimum of the total potential energy. In the case of
      adsorption the external potential exerted by the graphite layers is added to the
      free energy. The state of the interface zone between the liquid and the vapor
      phases or the state of the adsorbed phase is determined by the minimum of the
      grand potential. In the case of phase equilibrium the approach leads to the
      distribution of density and pressure over the transition zone. The interrelation
      between the collision diameter and the potential well depth was determined by the
      surface tension. It was shown that the distance between neighboring molecular
      layers substantially changes in the vapor-liquid transition zone and in the
      adsorbed phase with loading. The approach is considered in this paper for the
      case of adsorption of argon and nitrogen on carbon black. In both cases an
      excellent agreement with the experimental data was achieved without additional
      assumptions and fitting parameters, except for the fluid-solid potential well
      depth. The approach has far-reaching consequences and can be readily extended to
      the model of adsorption in slit pores of carbonaceous materials and to the
      analysis of multicomponent adsorption systems.

PMID- 16290857
TI  - Beta-casein bilayer adsorption at the solution/air interface: experimental
      evidences and theoretical description.
AB  - Ellipsometric and surface pressure studies of beta-casein adsorption layers at
      the water/air interface support the idea of a model that assumes the formation of
      a second layer adjacent to the primary adsorption layer. A thermodynamic model
      describes the concentration behavior of the surface pressure and the adsorbed
      amount with one and the same set of model parameters over the entire
      concentration range studied.

PMID- 16290858
TI  - Magneto-optics of Ferritin.
AB  - Measurements of Rayleigh light scattering, nonlinear light scattering in DC
      magnetic fields, and the Cotton-Mouton effect were carried out for 15 mM NaCl and
      water solutions of ferritin at room temperature. The spherical geometry of the
      molecule implies that it is optically isotropic. Such a macromolecule should not
      manifest magnetic anisotropy; however, in solution it shows induced magnetic
      birefringence (Cotton-Mouton effect) and changes in the intensity of the
      scattered light components. The analysis of the obtained results indicates the
      deformation of linear optical polarizability induced in the ferritin by a
      magnetic field as the main source of the magneto-optical phenomena observed.
      Light scattering and the CM effects theoretically depend on the linear magneto
      optical polarizability, chi, and the nonlinear magneto-optical polarizability,
      eta. Using the theory describing the phenomena as well as the experimental data,
      the values of the anisotropy of linear magneto-optical polarizability components,
      chi(parallel) - chi(perpendicular) = -(1.3 +/- 0.7) x 10(-22) [cm3] (in SI units
      chi(parallel) - chi(perpendicular) = -(2.0 +/- 1.2) x 10(-33) [m3]), the linear
      optical polarizability, alpha = (alpha(parallel) + 2alpha(perpendicular))/3 =
      (3.9 +/- 1.0) x 10(-20) [cm3] (in SI units alpha = (3.52 +/- 0.09)x10(-4) [Cm2 V(
      1)]), and its anisotropy, kappa(alpha) = (alpha(parallel) -
      alpha(perpendicular))/3alpha = -(0.06+/-0.03), nonlinear magneto-optical
      polarizability, eta = (eta(parallel) + 2eta(perpendicular))/3 = -(4.7 +/- 0.9) x
      10(-30) [cm3 Oe(-2)] (in SI units eta = -(6.7 +/- 1.3) x 10(-18) [Cm4 V(-1) A(
      2)]) and its anisotropy, kappa(eta) = (eta[parallel) - eta(perpendicular))/3eta =
      -(0.15 +/- 0.10), were deduced. Here alpha(parallel), eta(parallel),
      alpha(perpendicular), eta(perpendicular) are the optical and magneto-optical
      polarizability components along the parallel and the perpendicular axes of the
      axially symmetric molecule, respectively.

PMID- 16290859
TI  - Depletion flocculation of latex dispersion in ionic micellar systems.
AB  - The flocculation behavior of anionic and cationic latex dispersions induced by
      addition of ionic surfactants with different polarities (SDS and
      cetyltrimethylammonium bromide (CTAB)) have been evaluated by rheological
      measurements. It was found that in identical polar surfactant systems with
      particle surfaces of SDS + anionic lattices and CTAB + cationic lattices, a weak
      and reversible flocculation has been observed in a limited concentration region
      of surfactant, which was analyzed as a repletion flocculation induced by the
      volume-restriction effect of the surfactant micelles. On the other hand, in
      oppositely charged surfactant systems (SDS + cationic lattices and CTAB + anionic
      lattices), the particles were flocculated strongly in a low surfactant
      concentration region, which will be based on the charge neutralization and
      hydrophobic effects from the adsorbed surfactant molecules. After the particles
      stabilized by the electrostatic repulsion of adsorbed surfactant layers, the
      system viscosity shows a weak maximum again in a limited concentration region.
      This weak maximum was influenced by the shear rate and has a complete reversible
      character, which means that this weak flocculation will be due to the depletion
      effect from the free micelles after saturated adsorption.

PMID- 16290860
TI  - Formation of monodisperse polyacrylamide particles by radiation-induced
      dispersion polymerization: particle size and size distribution.
AB  - Polyacrylamide microparticles were directly produced by radiation-induced
      dispersion polymerization in aqueous alcohol media using poly(N-vinylpyrrolidone)
      as a steric stabilizer at room temperature. The hydrodynamic diameter of a
      polymer particle and its distribution were measured on a dynamic laser light
      scattering spectrometer. This method takes advantages of the specialties of
      radiation induction, and highly uniform polymer microspheres were obtained with
      high conversion. The number of the particle produced in the early stage of the
      polymerization was found to be constant during the remainder of the
      polymerization. The effects of various polymerization parameters, such as
      absorbed dose rate, monomer concentration, stabilizer content, medium polarity,
      and polymerization temperature on the particle size and size distribution were
      systematically investigated.

PMID- 16290861
TI  - Electroosmotic flow in a capillary annulus with high zeta potentials.
AB  - The electroosmotic flow through an annulus is analyzed under the situation when
      the two cylindrical walls carry high zeta potentials. The analytical solutions
      for the electric potential profile and the electroosmotic flow field in the
      annulus are obtained by solving the Poisson-Boltzmann equation and the Stokes
      equation under an analytical scheme for the hyperbolic sine function. A
      mathematical expression for the average electroosmotic velocity is derived in a
      fashion similar to the Smoluchowski equation. Hence, a correction formula is
      introduced to modify the Smoluchowski equation, taking into account contributions
      due to the finite thickness of the electric double layer (EDL) and the geometry
      ratio-dependent correction. Specifically, under a circumstance when the two
      annular walls are oppositely charged, the flow direction can be determined from
      the sign of such correction formula, and there exists a zero-velocity plane
      inside the annulus. With the assumption of large electrokinetic diameters, the
      location of the zero-velocity plane can be estimated from the analytical
      expression for the velocity distribution. In addition, the characteristics of the
      electroosmotic flow through the annulus are discussed under the influences of the
      EDL parameters and geometric ratio of the inner radius to the outer radius of the
      annulus.

PMID- 16290862
TI  - Hydrodynamics of a bounded vertical film with nonlinear surface properties.
AB  - The drainage of a thin liquid film with an insoluble monolayer down a vertical
      wall is studied. Lubrication theory is used to develop a model where the film is
      pinned at the top with a given thickness and the film drains into a bath at the
      bottom. A nonlinear equation of state is used for the surface tension and the
      surface viscosity is a nonlinear function of the surfactant concentration; these
      are appropriate for some aqueous systems. The three partial differential
      equations are solved via discretization in space and then the resulting
      differential algebraic system is solved. Results are described for a wide range
      of parameters, and the conditions under which the free surface is immobilized are
      discussed.

PMID- 16290863
TI  - Relationship between formation conditions, properties, and crystallite size of
      boehmite.
AB  - Boehmites (gamma-AlOOH) with a variety of crystallite sizes were prepared under
      various precipitation conditions from solutions of aluminum nitrate and sodium
      aluminate and also by hydrothermal treatment of a commercial boehmite powder. The
      relationships between the crystallite size and other properties of the boehmites
      were investigated. Crystalline boehmite was formed in the pH range 7 to 10 while
      gels precipitated below pH 7 and bayerite (Al(OH)3) formed at pH 11. The
      crystallite size of the boehmite increased at higher pH, higher temperature of
      the precursor solution, and longer aging time. As the crystallite size of the
      boehmite increased, the specific surface area, pore volume, and excess water
      decreased. Boehmites of small crystallite size, called pseudoboehmite, showed
      broadened X-ray peak widths and increased d-spacing of the 020 reflection. These
      changes are attributed to the small crystallite size (smaller numbers of stacking
      layers) and also to excess water in the interlayers of the boehmite structure.

PMID- 16290864
TI  - The permeability of synthetic fractal aggregates with realistic three-dimensional
      structure.
AB  - The permeability of fractal porous aggregates with realistic three-dimensional
      structure is investigated theoretically using model aggregates composed of
      identical spherical primary particles. Synthetic aggregates are generated by
      several techniques, including a lattice-based method, simulation of aggregation
      by differential settling and turbulent shear, and the specification of simple
      cubic structures, resulting in aggregates characterized by the number of primary
      particles, solid fraction, characteristic radius, and fractal dimension.
      Stokesian dynamics is used to determine the total hydrodynamic force on and the
      distribution of velocity within an aggregate exposed to a uniform flow. The
      aggregate permeability is calculated by comparing these values with the total
      force and velocity distribution calculated from the Brinkman equation applied
      locally and to the entire aggregate using permeability expressions from the
      literature. The relationship between the aggregate permeability and solid
      fraction is found to be best predicted by permeability expressions based on
      cylindrical rather than spherical geometrical elements, the latter tending to
      underestimate the aggregate permeability significantly. The permeability
      expressions of Jackson and James or Davies provide good estimates of the force on
      and flow through porous aggregates of known structure. These relationships are
      used to identify a number of general characteristics of fractal aggregates.

PMID- 16290865
TI  - A single-site model for divalent transition and heavy metal adsorption over a
      range of metal concentrations.
AB  - Metal adsorption data over a range of surface coverages typically are
      characterized by curvilinear metal adsorption isotherms. These isotherms
      generally have a slope of 1 at low surface coverage and a shallower slope at
      higher surface coverages. The curvature of metal adsorption isotherms with
      increasing surface coverage is frequently interpreted in terms of sequential
      adsorption onto different types of surface sites, multinuclear surface
      complexation, or nonideality of metal adsorption. We demonstrate that the
      curvature of metal adsorption isotherms can also be attributed to changes in
      surface charge and potential that depend on the predominant type of metal surface
      complex. A single-site extended triple-layer model is used to reinterpret
      previously studied metal adsorption isotherms and pH edges for a wide variety of
      metals (Cd2+, Co2+, Cu2+, Pb2+, and Zn2+) and solids (goethite, hydrous ferric
      oxide, corundum, and magnetite) in different electrolyte solutions (NaNO3 and
      NaClO4). Only metal adsorption on ferrihydrite at very low surface coverages is
      not consistent with the single-site triple-layer model. This discrepancy might be
      explained if ferrihydrite is in fact not a single phase but a mixture of two or
      more phases. Metal surface coverages ranging from 10(-4) to 10.2 mmol/m2 on the
      other minerals can be accounted for with a single-site extended triple-layer
      model if appropriate metal adsorption reactions are chosen. In addition, several
      examples suggest that, within the context of the model, surface complexation
      schemes can be established that describe metal adsorption over both a wide range
      of surface coverage and a wide range of ionic strength.

PMID- 16290866
TI  - Drop penetration into porous powder beds.
AB  - The kinetics of drop penetration were studied by filming single drops of several
      different fluids (water, PEG200, PEG600, and HPC solutions) as they penetrated
      into loosely packed beds of glass ballotini, lactose, zinc oxide, and titanium
      dioxide powders. Measured times ranged from 0.45 to 126 s and depended on the
      powder particle size, viscosity, surface tensions, and contact angle. The
      experimental drop penetration times were compared to existing theoretical
      predictions by M. Denesuk et al. (J. Colloid Interface Sci.158, 114, 1993) and S.
      Middleman ("Modeling Axisymmetric Flows: Dynamics of Films, Jets, and Drops,"
      Academic Press, San Diego, 1995) but did not agree. Loosely packed powder beds
      tend to have a heterogeneous bed structure containing large macrovoids which do
      not participate in liquid flow but are included implicitly in the existing
      approach to estimating powder pore size. A new two-phase model was proposed where
      the total volume of the macrovoids was assumed to be the difference between the
      bed porosity and the tap porosity. A new parameter, the effective porosity
      epsilon(eff), was defined as the tap porosity multiplied by the fraction of pores
      that terminate at a macrovoid and are effectively blocked pores. The improved
      drop penetration model was much more successful at estimating the drop
      penetration time on all powders and the predicted times were generally within an
      order of magnitude of the experimental results.

PMID- 16290867
TI  - Interfacial tension in phase-separated gelatin/dextran aqueous mixtures.
AB  - The effect of solute concentrations on interfacial tension was investigated in
      phase-separated mixtures of dextran and gelatin over a range of concentrations
      that covered different tie-lines and different positions on one tie-line. The
      investigations were carried out using equilibrated gelatin-rich and dextran-rich
      phases in a computer-controlled Couette device at 40 degrees C (above the
      gelation point of gelatin) and interfacial tensions were measured using the
      retracting drop method. The results show that the interfacial tension can be
      related to the length of the tie-line or to the difference in the concentration
      of dextran (or gelatin) in the separated phases. Interfacial tension increases as
      either of these parameters increases. For concentrations lying on any single tie
      line, the interfacial tension is constant and independent of the concentration of
      biopolymers. Also, the addition of small amounts of low molecular weight dextran
      to a dextran-rich phase does not significantly affect the interfacial tension
      between the gelatine-rich and dextran-rich phases. Experimental results were also
      compared with theoretical predictions of the interfacial tension using a Flory
      Huggins based analysis of the measured tie-line data. Reasonable agreement was
      found between predicted and measured values, indicating that this approach
      captures the basic physics of the system.

PMID- 16290868
TI  - Fluorescence evidence that a phase transition causes the induction time in the
      reduction in dynamic tension during surfactant adsorption to a clean air/water
      interface and a kinetic-diffusive transport model for the phase-induced
      induction.
AB  - An aqueous soluble surfactant adsorbing from solution onto an initially clean
      air/water interface often exhibits an induction period in the surface tension
      relaxation in which, as the adsorption begins, the tension remains near the clean
      interface value for an extended period of time before decreasing rapidly to the
      equilibrium value. In this study, using a model nonionic soluble surfactant,
      C14E6(CH3(CH2)13-(OCH2CH2)6-OH), we present direct fluorescence evidence that
      this induction is due to a first-order phase transition from a gaseous (G) to a
      liquid expanded (LE) phase that the assembling monolayer undergoes at constant
      surface pressure. An open channel flow cell is initially filled with water, and
      onto its air/water interface is spread an insoluble amphiphilic dye that
      fluoresces upon irradiation in the LE phase and whose fluorescence is quenched in
      the G phase. An aqueous solution of C14E(6) is then allowed to flow through the
      channel. We observe the immediate appearance of bright islands of the LE phase
      growing in a dark (G) background, confirming the presence of the G/LE phase
      transition. These islands eventually occupy the entire surface, after which the
      interface remains uniformly bright. We correlate this phase transition to the
      induction period by simultaneously measuring the tension of the interface of the
      open channel, and verifying that as the islands grow the tension remains at the
      clean value until the bright LE phase occupies the entire surface, whereupon the
      tension rapidly decreases. We further develop a phase transition surfactant
      transport model for the induction period in which surfactant diffuses toward and
      kinetically adsorbs onto the surface, and then rapidly equilibrates between the G
      and LE phases. For our model surfactant C14E6, we independently measure the
      surface concentration of the nucleating LE phase, the LE phase surfactant
      equation of state, the kinetic rate constants for adsorption into the LE phase,
      and the bulk diffusion coefficient. Using these measurements, we predict
      induction times for adsorption onto a clean surface without convection. We also
      measure these induction times in tension relaxation for adsorption onto a pendant
      bubble using axisymmetric shape analysis, and demonstrate agreement with the
      simulations with no adjustable constants.

PMID- 16290869
TI  - Fusion of vesicles in manganese complex of a single-chain schiff base amphiphile-
      3-cyano-N-benzylidene hexadecylamine.
AB  - A single-chain amphiphile containing a rigid Schiff base segment, 3-cyano-N
      benzylidene hexadecylamine (CNBHB) in the polar head group was synthesized and
      studied for its vesicle-forming properties. The dependence of the aggregation
      behavior of the vesicles as such and in the presence of manganese ions were
      studied as a function of temperature using differential scanning calorimetry and
      turbidity measurements. Transmission electron microscopy (TEM) was used to
      analyze the morphology of the vesicles, showed interesting features with fusion
      of regular structures, and were quite stable. In the presence of manganese ions,
      fusion of vesicles takes place. This could be due to the metal ions that are
      bound to the surface of the vesicles that cause a partial destruction of the
      hydration shell on the surface of the vesicles. The reduction in the hydration
      force could thus be responsible for the fusion.

PMID- 16290870
TI  - Determination of vesicle-water partition coefficients by electrokinetic
      chromatography: study of temperature effect.
AB  - Vesicular electrokinetic chromatography was used to investigate solute
      partitioning from the aqueous phase into dihexadecyl hydrogen phosphate (DHP)
      vesicles. Retention factors of neutral solutes are related to their partition
      coefficients between the aqueous phase and vesicles (K(vw)). The K(vw) of the
      aromatic test solutes were readily obtained from the slopes of the linear
      relationships between retention factors versus DHP concentrations. The technique
      offers the advantages of speed, automation, and small sample size for
      determination of partition coefficients. The K(vw) values of 43 uncharged solutes
      were measured at below as well as above the phase transition temperatures. The
      logarithms of partition coefficients (log K(vw)) of solutes at 71 degrees C
      (above T(c)) were slightly higher than those at 36 degrees C (below T(c)). The
      solvation characteristics of DHP were also studied using linear solvation energy
      relationships at the two temperatures.

PMID- 16290871
TI  - Selective foam separation of binary protein solution by SDS complexation method.
AB  - A fundamental study about the selective foam separation of protein mixture was
      carried out. A solution containing two proteins, ovalbumin (OA) and lysozyme
      (LZ), and an anionic surfactant, sodium dodecyl sulfate (SDS), was adjusted to pH
      6.0, which referred to an intermediate state between the isoelectric points of
      the proteins. The solution was processed by continuous foam separation. The
      results showed that a proper addition of SDS greatly improved the selective
      recovery of LZ to OA. The experimental data were well explained by a simple model
      that most of cationic protein molecules (LZ) are associated with SDS and the
      adsorption of all the species including LZ-SDS complexes are subjected to
      Langmuir adsorption isotherm. The results also showed that one of the Langmuir
      parameters, which means a kind of lyophillic property of adsorbed material, of LZ
      SDS complexes was extremely large as compared with that of primary protein.

PMID- 16290872
TI  - Coalescence during emulsification. 1. Method development.
AB  - A new method of measuring the amount of coalescence that occurs between drops
      during the emulsification process is proposed. The method uses a hydrophobic
      fluorescent probe, which is introduced into a fraction of the oil phase that is
      to be homogenized. The ratio of the intensity of the excimer peak to the
      intensity of the monomer peak in the fluorescent emission spectrum is sensitive
      to the concentration of the probe in the oil phase. Random coalescence events
      between oil drops lead to redistribution of the probe and its effective dilution
      in the oil phase. Coalescence results in a decrease in the intensity ratio in the
      fluorescence spectrum obtained from the ensemble of drops. Monte Carlo simulation
      is used to relate the change in intensity ratio to the coalescence rate. It is
      experimentally verified that the signal change is only due to coalescence and is
      not affected by the drop size of the distribution.

PMID- 16290873
TI  - Ultrafiltration of surfactant solutions.
AB  - The ultrafiltration of colloid solutions containing hexadecyltrimethylammonium
      bromide (CTAB), sodium dodecyl sulfate (SDS), and alkylpolyglucoside (APG)
      through hydrophilic membranes with a 10,000 mol wt cut-off from regenerated
      cellulose was studied. The effects of experimental conditions on the permeate
      flux and secondary resistance were determined. It was found that both CTAB and
      APG were convenient surfactants for ultrafiltration, as high permeability of
      their solutions was observed. The secondary resistance was always significantly
      lower than the resistance of the membrane. Additionally, electrolytes had a
      relatively weak negative effect upon ultrafiltration fluxes. SDS was the least
      convenient surfactant due to formation of a gel layer, susceptibility of its
      colloid solutions to electrolyte content, and a high secondary resistance. The
      concentration of the surfactant in the permeate could increase above critical
      micelle concentration, especially under conditions inducing high polarization.
      Migration of CTAB on the surface of pores seemed responsible for that transfer.

PMID- 16290874
TI  - Sandwich structures at oil-water interfaces under alkaline conditions.
AB  - Equilibrium liquid crystal (LC) layer on an interface between crude oils and
      water was observed at high pH. This layer is composed mainly of sodium
      naphthenates produced in situ at the water/oil interface. Transient LC layer was
      also evolved at the interface of aqueous phase of sodium hydroxide solutions and
      oleic phase of naphthenic acid (NA) solutions as result of a chemical reaction
      between NaOH and NA. This chemical reaction causes transport process resulting in
      a disturbance of the interface. Optical observation of this interface disturbance
      reviled that the interface covered with LC shows considerably lower flexibility
      as compared to LC free interface. The LC layer eventually dissolves in the water
      phase at low oil-to-water ratio, while at high oil-to-water ratio it can form an
      equilibrium phase, which spreads spontaneously at the oil-water interface.

PMID- 16290875
TI  - Complementary liposomes based on phosphatidylcholine: interaction effectiveness
      vs protective coating.
AB  - A prospective targeted drug delivery system was prepared by the introduction of
      complementary and protective moieties at the external surfaces of liposomes. Thus
      recognition between hydrogenated phosphatidylcholine-cholesterol-based liposomes
      was achieved by the interaction of the complementary phosphate and guanidinium
      groups incorporated in separate liposomes while polyethylene glycol chains (PEG)
      protected both liposomes from environmental factors. In general, protective
      coating of liposomes in the range of 5% molar incorporation exerted an inhibitory
      effect on their recognition but it also permitted effective interaction between
      complementary liposomes.

PMID- 16290876
TI  - Interfacial resistance in solubilization kinetics.
AB  - An experiment has been designed to measure the kinetics of solubilization of oils
      in a micellar solution. The results show a very large range of behaviors, but in
      one system the solubilization rate is determined completely by what is called the
      interfacial resistance, which quite likely arises out of the structural changes
      that micelles see. The model given here is successful in showing that this
      resistance is not the usual resistance due to diffusion and that it is quite
      prelevant in systems that are chemically similar but other conditions varying
      widely (Appendix). We conclude by showing that some of the existing theories of
      interfacial resistance are not reasonable, suggest how the real system may be
      more complex, and show that the interfacial conductance k* proportional c(m)(-1)
      at large surfactant concentrations where c(m) is the concentration of micelles.

PMID- 16290877
TI  - Rheological properties and orientational distributions of dilute ferromagnetic
      spherocylinder particle dispersions. Part II. Analysis for the two typical
      magnetic field directions.
AB  - We have investigated the orientational distributions and rheological properties
      of dilute colloidal dispersions, which consist of ferromagnetic spherocylinder
      particles. First, the governing equation of the orientational distribution
      function has been derived for the typical two cases of magnetic field directions:
      the direction parallel to the shear flow and the direction parallel to the
      angular velocity vector of the shear flow. The equation has been solved
      approximately by Galerkin's method. With these numerical solutions we have
      obtained the results of the orientational distribution and viscosity. The results
      obtained for the magnetic field in the shear flow direction are summarized as
      follows. In the case of a weak magnetic field, the particle tends to orient
      nearly toward the shear flow direction and its opposite direction. As the
      magnetic field increases, the orientation of the particle is restricted and the
      viscosity increases significantly. As the influence of the magnetic field becomes
      dominant, an overshoot in the viscosity curve appears. This is due to the fact
      that there is a maximum deviation of the averaged particle direction from the
      magnetic field direction. When the strength of the magnetic field increases
      significantly, the particle inclines close to the magnetic field direction and
      the viscosity converges to a constant value. Particles with a larger aspect ratio
      give rise to a larger increment in the viscosity since such elongated particles
      induce larger resistance in a flow field. We also have obtained results for the
      case of the magnetic field in the direction parallel to the angular velocity
      vector of the shear flow. When the flow field is dominant over both the
      rotational Brownian motion and the magnetic interaction, the particle rotates in
      the plane nearly perpendicular to the magnetic field direction. As the magnetic
      field increases, the particle inclines toward the magnetic direction. For this
      direction of field, the viscosity is independent of the magnetic field and is
      always zero.

PMID- 16290878
TI  - Synthesis and characterization of poly(ethylene oxide) star polymers possessing a
      tertiary amino group at each arm end by organized polymerization using
      macromonomers.
AB  - Functional poly(ethylene oxide) star polymers possessing a tertiary amino group
      at each arm end were prepared by free-radical copolymerization of poly(ethylene
      oxide) macromonomers with divinylbenzene (DVB) in water or ethanol. The
      poly(ethylene oxide) arm was prepared by anionic polymerization using 2-[2-(N,N
      dimethylamino)ethoxy]ethanol potassium alkoxide as the initiator. The star
      polymers had narrow molecular weight distribution. The arm number was controlled
      by varying the feed ratio [DVB]/[M], the initial concentration of macromonomer
      [M], and solvent media. The branching factor g' in methanol ([eta]S/[eta]L are
      the intrinsic viscosities of the star and linear molecules, respectively)
      exhibited a power-law dependence on the arm number, f, with a negative exponent.
      This means that the dimensions of a star were in agreement with the Daoud-Cotton
      scaling model.

PMID- 16290879
TI  - Hydrophobicity of peritoneal tissues in the rat.
AB  - In this study, an inventory of the hydrophobicity of peritoneal tissues in the
      living rat was made. Peritoneal tissues were divided into mesentery (i.e.,
      omentum) and parietal and visceral peritoneum and their hydrophobicity was
      determined by the sessile drop method. All peritoneal tissues were hydrophilic
      with water contact angles varying from 0 degrees to 61 degrees. Mesentery and
      visceral peritoneum covering the intestines were significantly more hydrophilic
      than parietal and other visceral peritoneal tissues. In general, visceral
      peritoneum was the most hydrophobic tissue, and visceral peritoneum covering the
      kidneys (61 degrees) and the stomach (54 degrees) was less hydrophilic than that
      covering the rest of the organs, i.e., spleen (49 degrees), liver (45 degrees),
      and bladder (41 degrees). In summary, peritoneal tissues involved in adsorptive
      and exchange functions and requiring lubrication are more hydrophilic than
      tissues with more important and protective functions.

PMID- 16290880
TI  - Washburn's equation facing Galileo's transformation: some remarks.
AB  - Capillary rise is the basis of some methods employed for the determination of
      contact angles in porous materials. One of them consists of the measuring of the
      distance the liquid advances into the pores of the solid. Normally, the results
      are analyzed by a rectilinear fitting to Washburn's equation. However, if it is
      taken into account that the distance-time measurements can be made under numerous
      reference systems and that, therefore, Galileo's transformations must be
      considered, it can be proved that the analysis of the results has to be carried
      out by parabolic expression of Washburn's equation. Even more, this work
      demonstrates theoretically that the traditional expression of Washburn's equation
      is valid only to describe the distance-time measurements got from that place
      where the initial contact between the porous solid and the liquid is established.

PMID- 16290882
TI  - 2005: a year of accreditation, collaboration, and setting standards-landmarks for
      the Partnership and Gender Medicine.

PMID- 16290883
TI  - Interdisciplinary research on women's health and sex/gender factors.

PMID- 16290884
TI  - Gonzales v Raich: the US supreme court's consideration captured the public policy
      debate about the medical use of marijuana.

PMID- 16290885
TI  - Sex- and gender-based medicine: venus, mars, and beyond.

PMID- 16290886
TI  - Sex differences in pain perception.
AB  - BACKGROUND: A number of studies have demonstrated a higher prevalence of chronic
      pain states and greater pain sensitivity among women compared with men. Pain
      sensitivity is thought to be mediated by sociocultural, psychological, and
      biological factors. OBJECTIVE: This article reviews laboratory studies that
      provide evidence of sex differences in pain sensitivity and the response to
      analgesic drugs in animals and humans. The biological basis of such differences
      is emphasized. METHODS: The literature from this relatively new field was
      surveyed, and studies that clearly illustrate the differences in pain mechanisms
      between the sexes are presented. Using the search terms sex, gender, and pain, a
      review was conducted of English-language literature published on MEDLINE between
      January 1980 and August 2004. RESULTS: Although differences in pain sensitivity
      between women and men are partly attributable to social conditioning and to
      psychosocial factors, many laboratory studies of humans have described sex
      differences in sensitivity to noxious stimuli, suggesting that biological
      mechanisms underlie such differences. In addition, sex hormones influence pain
      sensitivity; pain threshold and pain tolerance in women vary with the stage of
      the menstrual cycle. Imaging studies of the brain have shown differences between
      men and women in the spatial pattern and intensity of response to acute pain.
      Among rodents, females are more sensitive than males to noxious stimuli and have
      lower levels of stress-induced analgesia. Male rodents generally have stronger
      analgesic response to mu-opioid receptor agonists than females. Research on
      transgenic mice suggests that normal males have a higher level of activity in the
      endogenous analgesic system compared with normal females, and a human study has
      found that mu-receptors in the healthy female brain are activated differently
      from those in the healthy male brain. The response to kappa-opioids, which is
      mediated by the melanocortin-1 receptor gene in both mice and humans, is also
      different for each sex. CONCLUSION: Continued research at the genetic and
      receptor levels may support the need to develop gender-specific drug therapies.

PMID- 16290887
TI  - Role of corticotropin-releasing factor pathways in stress-related alterations of
      colonic motor function and viscerosensibility in female rodents.
AB  - BACKGROUND: Clinical reports have shown that irritable bowel syndrome (IBS) is
      comorbid with anxiety/depression and stress-related events, and that the disorder
      is more prevalent among women than among men. In rodents, colorectal distention
      (CRD) induces abdominal contractions, and this visceromotor response is used to
      assess visceral pain. The activation of brain corticotropin-releasing factor
      (CRF) pathways has a key role in the behavioral and visceral responses to stress.
      OBJECTIVE: In this review of experimental studies that delineate the underlying
      mechanisms of the stress response, we focused on CRF signaling pathways and sex
      hormones in modulating visceral hypersensitivity induced by CRD in rodents.
      METHODS: The findings of our recent research on the development of an
      experimental model of visceral pain in female rats and the modulation of the
      hyperalgesic response to CRD by CRF antagonists were integrated with those of the
      published literature. A MEDLINE search of the years 1981 to 2005 was conducted
      using the key words stress, CRF, CRH, CRF1 receptor, IBS, CRD, female rat,
      visceral pain, estrogen, and anxiety. RESULTS: CRF and other related mammalian
      peptides (urocortins) interact with the distinct CRF subtype 1 and 2 receptors.
      Well-documented preclinical studies have established the role of brain CRF1
      receptors in mediating stress-related anxiogenic and visceral (stimulation of
      colonic motor function and sensitization to repeated CRD) responses in male
      rodents, whereas more limited studies have been performed in female rats. Our
      recent study indicated that the CRF1 antagonist antalarmin prevents visceral
      hypersensitivity induced by 2 sets of CRD in female rats. In several models of
      visceral pain induced by CRD, sex differences and a sensitization action of
      estrogen were reported. Our preliminary evidence indicated a potentiating
      interaction between CRF-CRF1 pathways and estrogen in the stimulation of colonic
      motor responses that may take place within the enteric neurons of the colon,
      where both CRF1 and estrogen receptors are present. CONCLUSIONS: The results of
      this review suggest that overactivity of CRF1 signaling in the brain and the gut
      may have relevance in understanding the comorbidity of anxiety/depression and IBS
      in diarrhea-predominant female patients. Targeting these mechanisms with CRF1
      antagonists may provide a novel therapeutic strategy.

PMID- 16290888
TI  - Effects of experimental hyperandrogenemia on the female rat reproductive axis:
      suppression of progesterone-receptor messenger RNA expression in the brain and
      blockade of luteinizing hormone surges.
AB  - BACKGROUND: Preovulatory gonadotropin-releasing hormone and luteinizing hormone
      (LH) surges depend on activation of estrogen-inducible progesterone receptors
      (PRs) in the hypothalamus. Although testosterone treatment can suppress LH
      secretion under some circumstances, how androgens affect the release of
      preovulatory hormone surges, and the cellular mechanisms by which androgens exert
      any such effects, remains unknown. OBJECTIVE: This study examined the hypothesis
      that testosterone can block the release of estrogen-induced gonadotropin surges
      via attenuation of estrogen's ability to induce PRs in the preoptic area (POA)
      hypothalamus. METHODS: In experiment 1, proestrus rats were implanted with
      capsules filled with crystalline testosterone or empty control capsules. Four
      days later, animals were bled via atrial catheters at 30-minute intervals from
      noon to 9:00 pm. In experiment 2, proestrus rats received testosterone-filled or
      empty control capsules, and 3 days later were ovariectomized (OVX) and injected
      with estradiol benzoate (EB) 30 mug SC or sesame oil vehicle. The next day, blood
      samples were obtained from the rats. In experiment 3, proestrus rats similarly
      implanted with testosterone-filled or empty control capsules, OVX, and injected
      with EB or vehicle were sacrificed, and POA-hypothalamic tissue was collected for
      quantitative reverse transcription-polymerase chain reaction analysis of PR
      messenger RNA. RESULTS: In experiment 1, radioimmunoassay of serum revealed that
      testosterone completely blocked release of LH surges that were fully evident in
      the control group. In experiment 2, LH radioimmunoassay revealed that high
      physiologic testosterone exposure completely abolished the release of EB-induced
      LH surges. In experiment 3, although EB treatment was found to induce an increase
      in PR expression in control animals, no such induction of PR expression was
      observed in the testosterone-treated rats. CONCLUSIONS: Our findings are
      consistent with the hypothesis that hyperandrogenic interference in the release
      of preovulatory LH surges is mediated by the suppressive effects of androgens on
      PR expression in POA-hypothalamic tissue. These findings may have important
      implications in the understanding of reproductive dysregulation in female
      hyperandrogenic syndromes, including polycystic ovary syndrome.

PMID- 16290889
TI  - Racial differences among reasons for participating in research of pregnancy
      outcomes: the right from the start experience.
AB  - BACKGROUND: Historically, racial minorities and women are less likely to
      participate in medical research than are whites and men. Although much is known
      about barriers to enrollment for those who decline to participate, much less is
      known about factors that motivate those who choose to enroll. OBJECTIVE: This
      study examines the reasons for participation in pregnancy outcomes research and
      determines whether these reasons varied by race. METHODS: Right From The Start is
      an ongoing prospective cohort study. Pregnant women aged >or=18 years, who
      enrolled in and completed the study between December 2000 and June 2003, were
      interviewed by telephone at the conclusion of their participation and asked about
      motivators for enrolling. Univariate and bivariate statistics were used to
      determine the relationship between self-identified race and main reason for
      participating in the study. Logistic regression was used to adjust for the
      influence of age, gravidity, education, marital status, and income. RESULTS: A
      total of 1106 women were interviewed: 735 (66.5%) whites; 285 (25.8%) blacks; 30
      (2.7%) Hispanics; and 56 (5.1%) others (Asians, Pacific Islanders). Black women
      listed a free ultrasound (73/247, 29.6%), contribution to medical knowledge
      (60/247, 24.3%), wanting to learn about pregnancy health (46/247, 18.6%), and
      concern about pregnancy health (30.247, 12.1%) as their main reason for
      participation. Black women were significantly less likely than white women to
      cite contribution to medical knowledge as the main reason for participation (odds
      ratio [OR] = 0.44; 95% CI, 0.36-0.63). Blacks were more likely than whites to
      list wanting to learn about pregnancy health (OR = 3.12; 95% CI, 1.88-5.55) or
      concern about pregnancy health (OR = 3.0; 95% CI, 1.56-5.94), even after
      adjusting for age, gravidity, pregnancy loss, education, marital status, and
      income. CONCLUSIONS: Access to free pregnancy ultrasounds and contribution to
      medical knowledge were important motivators for both white and black women.
      However, whereas black women were more likely to report concerns about pregnancy
      health or pregnancy health education as the main reason for participation, white
      women were more likely to report a desire to contribute to medical knowledge.

PMID- 16290890
TI  - Neuroimaging study of sex differences in the neuropathology of cocaine abuse.
AB  - BACKGROUND: Female and male substance abusers differ in their disease patterns
      and clinical outcomes. An important question in addiction neuroscience thus
      concerns the neural substrates underlying these sex differences. OBJECTIVE: This
      article aims to examine what is known of the neural mechanisms involved in the
      sex differences between substance abusers. METHODS: We reviewed neuroimaging
      studies that addressed sex differences in cerebral perfusion deficits after
      chronic cocaine use and in regional brain activation during pharmacologic
      challenge and cue-induced craving. We also present results from a preliminary
      study in which cocaine-dependent men and women participated in script-guided
      imagery of stress- and drug cue-related situations while blood oxygenation level
      dependent signals of their brain were acquired in a 1.5T scanner. Spatial pre
      processing and statistical analysis of brain images were performed. Regional
      brain activation was compared between stress and drug cue trials in men versus
      women. RESULTS: The results of our study showed greater activation in the left
      uncus and right claustrum (both, statistical threshold of P = 0.01, uncorrected;
      extent = 10 voxels) in men (n = 5) during drug cue trials compared with stress
      trials. No brain regions showed greater activation during stress trials compared
      with drug cue trials. In contrast, women (n = 6) showed greater activation in the
      right medial and superior frontal gyri during stress trials compared with drug
      cue trials at the same statistical threshold. No brain regions showed more
      activation during drug cue trials than during stress trials. CONCLUSIONS: The
      studies reviewed underscore the need to consider sex-related factors in examining
      the neuropathology of cocaine addiction. Our preliminary results also suggest
      important sex differences in the effect of stress- and drug cue-associated brain
      activation in individuals with cocaine use disorder.

PMID- 16290892
TI  - Novel approaches to radiotherapy-induced skin reactions: a literature review.
AB  - Patients undergoing radiotherapy treatment will receive some degree of skin
      damage. Internationally there are many preventative and treatment options
      recommended, with varying degrees of evidence of success. This review explores
      the possible benefits of various plant-based treatments within the context of
      other novel treatments. The evidence suggests that using a hydrophilic substance
      such as Aloe vera gel or vegetable oil that is high in essential fatty acids, is
      as effective as mild steroid creams such as 1% hydrocortisone in reducing the
      severity of reactions. Additionally with plant-based treatments there does not
      appear to be side effects such as may occur with steroids. There remains great
      scope for further studies either replicating some of these current studies or
      exploring other options such as the use of essential oils or other herbal
      extracts.

PMID- 16290893
TI  - Life chance characteristics of older users of Swedish massage.
AB  - The characteristics of those who use complementary and alternative medicine
      (CAM), as an approach to chronic disease management, are poorly understood. They
      may however be important to nurses and other health professionals given that CAM
      is increasingly used by their patients with chronic disorders. In these contexts,
      the purpose of this study was to ascertain unique life chance population
      characteristics which significantly influence the use of Swedish massage therapy
      (SMT), a popular form of CAM, by older adults with chronic health dysfunctions. A
      multi-site and cross-sectional design was used, as well as a pre-tested postal
      questionnaire. One hundred forty-one (141) urban, non-institutionalized, English
      speaking older persons participated, ranging in age from 60 to 94 years. Findings
      denote the essential role life chances have on individuals accessing alternative
      forms of care.

PMID- 16290894
TI  - Effects of Swedish massage on blood pressure.
AB  - Swedish massage technique includes mechanically activated muscular tissue and
      also skin, tendons, fascias, and connected tissue, which indirectly regulates the
      tonus of the autonomous nervous system. This study set out to examine the effects
      of Swedish massage on blood pressure. Healthy males were given massage treatment
      at the Karolinska Hospital, Stockholm, Sweden. Treatment was over a 12-week
      period divided into three parts, each consisting of 4 weeks. Two treatment
      periods contained massage treatment either on back, neck and chest (BNC), or leg,
      arm and face (LAF), with an in between washout period. The first treatment period
      with massage decreased systolic blood pressure directly after treatment (BNC:
      P<0.005, LAF: P<0.01), but no significant changes were seen in diastolic blood
      pressure. In the second period, BNC massage decreased systolic (P<0.005) and
      diastolic (P<0.005) blood pressure whereas LAF massage (P<0.05) increased
      systolic blood pressure. Swedish massage on the BNC resulted in a minor decrease
      in blood pressure possibly due to sympathetic inhibition. It may be suggested
      that massage may be tried as a complementary therapy in patients suffering from
      increased blood pressure due to stress.

PMID- 16290895
TI  - Using qualitative evaluation in a feasibility study to improve and refine a
      complementary therapy intervention prior to subsequent research.
AB  - Feasibility studies of complementary therapies are useful and important not only
      to test and evaluate the potential effectiveness of an intervention but also to
      refine and improve it prior to a subsequent study. A series of guided interviews
      were conducted with patients (n=19) undergoing stem cell/autologous bone marrow
      transplant (SC/ABMT) who were participating in a feasibility study of a
      mindfulness meditation (MM) intervention. Audiotapes of these interview sessions
      were transcribed and then used to create a project in the QRS NVivo software
      program to manage the data from the interview questions. Responses about what the
      participants liked and disliked and their suggestions for improving the
      effectiveness of the MM intervention were identified and grouped. Subsequently,
      the MM intervention has been refined based on this information, and additional
      testing in a randomized, controlled trial is planned. The cost is high to
      implement complementary therapies and to rigorously test them. Preliminary work
      using qualitative evaluation methods can provide rich and detailed information
      that will save time and money in the long run.

PMID- 16290896
TI  - Addressing efficiency: economic evaluation and the agenda for CAM researchers.
AB  - Considerations of efficiency are increasingly part of the broad agenda for
      evidence-based practice in conventional medicine. The findings of applied
      economic evaluations are often combined with other forms of evidence to assist
      clinical and wider resource decisions. It follows that as complementary and
      alternative medicine (CAM) strives for further integration into conventional
      health services, it might also be subjected to such scrutiny. In preparation for
      this, this paper provides a basic yet critical introduction to applied economic
      evaluation; the types of techniques used, their broad strengths and weaknesses,
      related ethical and moral debate and, in particular, specific issues concerning
      their application to CAM. Readers will decide for themselves whether they might
      be supportive of, or opposed to, economic evaluation and under what
      circumstances. Nevertheless, a wide-ranging agenda for research on economic
      evaluation and CAM is presented and some basic methodological and design issues-
      including place specificities and sensitivities--are highlighted.

PMID- 16290897
TI  - Rapport: a key to treatment success.
AB  - The therapeutic relationship is a concept often ignored in current literature. As
      such, the importance of good patient rapport may be overlooked. To address these
      concerns, the following paper highlights the effects that strong therapeutic
      relationships may have on patient satisfaction, treatment compliance and client
      outcomes. Strategies that practitioners can employ to facilitate the development
      of good patient rapport are also discussed.

PMID- 16290898
TI  - Menstrual cycle and Yin-Yang in healthy nursing college students.
AB  - The aim of this study was to investigate the relationship between several
      menstrual characteristics and Yin-Yang, using the traditional Korean Sasang
      typology in 565 female college students. Using the questionnaire for the Sasang
      Constitution Classification, which consists of 121 forced-choice items, subjects
      were classified into three groups: So-Yang (small Yang, n=194), Tae-Eum (large
      Yin, n=164) and So-Eum (small Yin, n=207). Tae-Eum-type subjects showed
      significantly higher body mass index (BMI) values than other types. There was
      also a significant difference in menstrual duration between the Tae-Eum and So
      Eum groups. However, there were no differences in the cycle or pattern of
      menstruation, or in the amount of menstrual blood among the groups. There were
      also no significant differences in the menstrual variables between Yin and Yang
      subjects. In conclusion, our results regarding the relationship between menstrual
      cycle and Yin-Yang types are inconsistent with traditional theory. However, this
      study shows that menstrual duration and BMI differ significantly among Sasang
      types.

PMID- 16290899
TI  - Self-healing interventions for clinical practice: brief psychotherapy with WHEE-
      the wholistic hybrid of EMDR and EFT.
AB  - Potent self-healing approaches are now available to help people to deal with
      their stresses, anxieties and pains of physical and emotional origins. The
      author, a wholistic psychiatrist, shares his clinical experiences in helping his
      clients deal expeditiously and successfully with a variety of physical and
      psychological symptoms. This article focuses on WHEE, a brief, potent method for
      releasing psychological and physical pains, negative beliefs and disbeliefs, and
      for installing positive feelings and beliefs. To use modern terminology, this
      method allows you to correct the serious but not fatal error you have made in
      letting a child program your lifetime computer. WHEE is a method for
      reprogramming your default programs.

PMID- 16290901
TI  - Protein interactions and misfolding analyzed by AFM force spectroscopy.
AB  - Protein misfolding is conformational transition dramatically facilitating the
      assembly of protein molecules into aggregates of various morphologies.
      Spontaneous formation of specific aggregates, mostly amyloid fibrils, was
      initially believed to be limited to proteins involved in the development of
      amyloidoses. However, recent studies show that, depending on conditions, the
      majority of proteins undergo structural transitions leading to the appearance of
      amyloidogenic intermediates followed by aggregate formation. Various techniques
      have been used to characterize the protein misfolding facilitating the
      aggregation process, but no direct evidence as to how such a conformational
      transition increases the intermolecular interactions has been obtained as of yet.
      We have applied atomic force microscopy (AFM) to follow the interaction between
      protein molecules as a function of pH. These studies were performed for three
      unrelated and structurally distinctive proteins, alpha-synuclein, amyloid beta
      peptide (Abeta) and lysozyme. It was shown that the attractive force between
      homologous protein molecules is minimal at physiological pH and increases
      dramatically at acidic pH. Moreover, the dependence of the pulling forces is
      sharp, suggesting a pH-dependent conformational transition within the protein.
      Parallel circular dichroism (CD) measurements performed for alpha-synuclein and
      Abeta revealed that the decrease in pH is accompanied by a sharp conformational
      transition from a random coil at neutral pH to the more ordered, predominantly
      beta-sheet, structure at low pH. Importantly, the pH ranges for these
      conformational transitions coincide with those of pulling forces changes detected
      by AFM. In addition, protein self-assembly into filamentous aggregates studied by
      AFM imaging was shown to be facilitated at pH values corresponding to the maximum
      of pulling forces. Overall, these results indicate that proteins at acidic pH
      undergo structural transition into conformations responsible for the dramatic
      increase in interprotein interaction and promoting the formation of protein
      aggregates.

PMID- 16290902
TI  - Conformation biases of amino acids based on tripeptide microenvironment from PDB
      database.
AB  - We have constructed a bank (FTTP) of tendentious factors of three states of three
      peptide units from PDB database based on conformational dihedral angle library
      and demonstrated that amino acid biases toward protein secondary structure are
      present in natural protein sequences. Our research results reveal that 20
      standard amino acids fall into three groups: nine residues inclined to alpha
      helix with a common character (e.g. direct side chain aliphatic residues or
      positive/negative charged residues) arrange in three grades, viz EA, QKRLD, and
      MN, in turn; seven residues are apt to beta-strand with 2'-branched side chain
      aliphatic residues or benzyl-included residues, namely PV, IYTC, and F, in three
      ranks; and four residues SHWG show a double tendency to both alpha and beta.
      Noticeably, proline has the strongest ability to form extended conformation,
      especially the Re value up to 9.5298 at position 3 (Table 3). Thus, biases of
      codons show an evident tendency in protein folding, where GC-rich codons are
      mainly in charge of forming contracted conformation, especially the codon's first
      letter plays a dominant role in translating the genomic GC signature into protein
      sequences and structures. So, biases of amino acids will play an important role
      in protein folding, folding codons, refining domain, structure prediction, and
      structural genomics/proteomics.

PMID- 16290903
TI  - Zero-valent iron pretreatment for enhancing the biodegradability of RDX.
AB  - Hexahydro-1,3,5-trinitro-1,3,5-triazine (C3H6N3(NO2)3, royal demolition explosive
      or RDX) is a common nitramine explosive and one of the major constituents in
      wastewaters from ammunitions plants. The objective of this study is to
      investigate zero-valent iron (Fe0) pretreatment for enhancing the
      biodegradability of recalcitrant RDX. It was hypothesized that iron pretreatment
      can reductively transform RDX to products that are more amenable to biological
      treatment processes such as activated sludge. Results of batch and column
      experiments showed rapid and complete removal of RDX by Fe0 regardless of the
      buffering capacity. Formaldehyde (HCHO), a major reduction product of RDX, was
      readily biodegraded by a mixed culture. Respirometric data indicate that iron
      treated RDX solution exerted substantially higher biochemical oxygen demand (BOD)
      than untreated RDX solution. We propose that an integrated iron reduction
      activated sludge process may be a feasible option for treating RDX-laden
      wastewater.

PMID- 16290905
TI  - Self-activating nuclease activity of copper (II) complexes of hydroxyl-rich
      ligands.
AB  - Copper (II) complexes of Schiff bases derived from [1+1] condensation of
      salicylaldehyde, 2,3-dihydroxybenzaldehyde and 2,3,4-trihydroxybenzaldehyde with
      anthranilic acid (L1-L3) have been synthesized and characterized by elemental
      analyses, IR, UV-Vis spectra, room temperature magnetic susceptibility, electron
      paramagnetic resonance spectroscopy and cyclic voltammetry. The X-ray structure
      of [CuL1]n has been solved and refined to R = 0.0314. The crystals are monoclinic
      with space group P2(1) with cell constants a = 9.6820(13), b = 7.1446(11), c =
      9.9315(13) A, beta = 98.385(8) degrees, Z = 2. The copper (II) ions are in a
      distorted tetrahedral environment sequentially bridged by carboxylate groups in
      the syn-anti conformation giving rise to a helix-like chain. The copper complexes
      with the inherent redox active hydroquinone functionality cleave plasmid pBR322
      DNA without exogenous agents by a self-activating mechanism.

PMID- 16290904
TI  - Synthesis and evaluation of poly(diol citrate) biodegradable elastomers.
AB  - Herein, we report the synthesis and evaluation of a novel family of biodegradable
      and elastomeric polyesters, poly(diol citrates). Poly(diol citrates) were
      synthesized by reacting citric acid with various diols to form a covalent cross
      linked network via a polycondensation reaction without using exogenous catalysts.
      The tensile strength of poly(diol citrates) were as high as 11.15+/-2.62 MPa and
      Young's modulus ranged from 1.60+/-0.05 to 13.98+/-3.05 MPa under the synthesis
      conditions that were investigated. Elongation was as high as 502+/-16%. No
      permanent deformation was found during mechanical tests. The equilibrium water-in
      air contact angles of measured poly(diol citrates) films ranged from 15 degrees
      to 53 degrees . The mechanical properties, degradation and surface
      characteristics of poly(diol citrates) could be controlled by choosing different
      diols as well as by controlling the cross-link density of the polyester network.
      Various types of poly(diol citrate) scaffolds were fabricated to demonstrate
      their processing potential. These scaffolds were soft and could recover from
      deformation. In vitro and in vivo evaluation using cell culture and subcutaneous
      implantation, respectively, confirmed cell and tissue compatibility. The
      introduction of poly(diol citrates) will expand the repertoire of currently
      available biodegradable polymeric elastomers and should help meet the
      requirements of tissue engineering applications.

PMID- 16290906
TI  - What is the current treatment of PTLD after liver transplantation?

PMID- 16290908
TI  - Fifth forum on liver transplantation.

PMID- 16290907
TI  - Efficacy of 24 weeks treatment with peginterferon alfa-2b plus ribavirin in
      patients with chronic hepatitis C infected with genotype 1 and low pretreatment
      viremia.
AB  - BACKGROUND/AIMS: Previous studies using standard interferon and ribavirin
      combination therapy suggested that patients infected with HCV-1 and a low
      pretreatment HCV-RNA level can be treated for 24 weeks without compromising
      sustained virologic response rates. The aim of the present study was to
      investigate this schedule in the era of pegylated interferon-alpha plus
      ribavirin. METHODS: Patients chronically infected with HCV-1 (n=235) and a
      screening viremia < or =600,000 IU/mL (real-time PCR) were treated with
      peginterferon alfa-2b 1.5 microg/kg subcutaneously once weekly plus ribavirin 800
      1400 mg/day based on body weight for 24 weeks. RESULTS: End-of-treatment and
      sustained virologic response rates were 80 and 50%, respectively. The 48-week
      historical control (Manns et al., Lancet 2001;358:958-65) had similar end-of
      treatment (74%) but higher sustained virologic response rates (71%). This
      difference was due to a high virologic relapse rate after 24 weeks of therapy
      (37%) compared with the historical control (4%). A subset of patients who had
      undetectable serum HCV-RNA at treatment week 4, however, achieved similar
      sustained virologic response rate (89%) as in the control group (85%).
      CONCLUSIONS: HCV-1 infected patients with a low baseline HCV-RNA concentration
      who become HCV-RNA negative at week 4 may be treated for 24 weeks without
      compromising sustained virologic response rates.

PMID- 16290909
TI  - Skin cancers after liver transplantation: what to do?

PMID- 16290910
TI  - The significance of extensor tendon tethering and dorsal joint capsule tightening
      after injury to the hand.
AB  - This paper examines the clinical problem of extensor tendon tethering and/or
      dorsal joint capsule tightening secondary to hand injury. One hundred and forty
      one patients were examined 13 to 51 months after hand injuries of varying
      severity. Fifty-six patients (40%) had suffered simple and eighty-five patients
      (60%) complex injuries. Seventy-four (52%) of the 141 patients had no extensor
      tendon tethering and/or dorsal joint capsule tightening. In 30 (21%), the
      extensor tendon tethering and/or dorsal joint capsule tightening was considered
      to be "obvious" in that it was easily seen on examination using various commonly
      used clinical tests of finger flexion and extension. In 37 (26%), the extensor
      tendon tethering and/or dorsal joint capsule tightening was considered to be of
      "lesser degree" because it was only evident on application of specific tests
      which are described in this paper. Of the 37, 21 (56%) described themselves as
      being unable to make a "proper" fist with the injured hand, 33 (89%) had pain or
      discomfort on the dorsum of the injured hand and/or fingers on gripping (P <
      0.01) and 25 (70%) had weakness of power of gripping (P < 0.01). Thirty-two (87%)
      complained of functional problems at work, with activities of daily living or
      with the pursuit of their hobbies.

PMID- 16290911
TI  - Carpal tunnel syndrome and flexion contracture of the digits in a child with
      familial hypercholesterolaemia.
AB  - This paper presents a 9 year-old girl who had flexion contracture of digits,
      carpal tunnel syndrome and multiple xanthomas covering the extremities.

PMID- 16290912
TI  - The S-Quattro in the management of acute intraarticular phalangeal fractures of
      the hand.
AB  - Intraarticular phalangeal fractures of the hand are difficult and challenging to
      manage. Dynamic external fixation devices offer the advantages of allowing
      distraction of the impacted fracture and early joint mobilization. We present our
      study of 100 patients with a variety of fractures who were treated with the S
      Quattro technique over a 6-year period, with an average follow-up of 10.5 months.
      The mean active range of motion regained was 92 degrees for proximal
      interphalangeal joints (81 fractures), 82 degrees for distal interphalangeal
      joints (10 fractures), 91 degrees for metacarpophalangeal joints (6 fractures)
      and 80 degrees for interphalangeal joints of the thumb (3 fractures). Only nine
      patients complained of mild or moderate pain. Postoperative radiographic
      appearances were satisfactory in all but five out of the 100 patients. This
      device is a simple and effective technique for the management of these difficult
      fractures. It offers advantages in terms of versatility, ease of application,
      good tolerance by patients, few complications and good outcome.

PMID- 16290914
TI  - Ulnar nerve compression in Guyon's canal in the presence of a tortuous ulnar
      artery.
AB  - A case of ulnar nerve compression in Guyon's canal occurring in the presence of a
      tortuous ulnar artery in the canal is presented and the pathology and
      classification of ulnar nerve compression in Guyon's canal discussed.

PMID- 16290913
TI  - Scaphoid and capitate fracture with concurrent scapholunate dissociation.
AB  - Combined fracture of the scaphoid and capitate bones with concurrent scapholunate
      dissociation, but without severe dislocation, is a rare lesion which results in
      significant carpal instability and requires operative treatment. We report a case
      of this unusual injury and its functional result after 20 months.

PMID- 16290915
TI  - Growth and nutritive quality of Poa pratensis as influenced by ozone and
      competition.
AB  - Interspecific plant competition has been hypothesized to alter effects of early
      season ozone (O3) stress. A phytometer-based approach was utilized to investigate
      O3 effects on growth and nutritive quality of Poa pratensis grown in monoculture
      and in mixed cultures with four competitor-plant species (Anthoxanthum odoratum,
      Achillea millefolium, Rumex acetosa and Veronica chamaedrys). Mesocosms were
      exposed during April/May 2000-2002 to charcoal-filtered air+25 ppb O3 (control)
      or non-filtered air+50 ppb O3 (elevated O3). Biomass production was not affected
      by O3, but foliar injury symptoms were observed in May 2002. Early-season O3
      exposure decreased relative food value of P. pratensis by an average of 8%, which
      is sufficient to have nutritional implications for its utilization by herbivores.
      However, forage quality response to O3 was not changed by interspecific
      competition. Lack of injury and nutritive quality response in P. pratensis
      harvested in September may reflect recovery from early-season O3 exposure.

PMID- 16290916
TI  - Living in the shadow of terrorism: psychological distress and alcohol use among
      religious and non-religious adolescents in Jerusalem.
AB  - This study examines the effects of prolonged exposure to terrorism in 600
      religious and non-religious Jewish adolescents living in Jerusalem, particularly
      post-traumatic stress (PTS) symptoms, depressive symptoms, alcohol use, coping
      strategies and social support. The youth in Jerusalem reported high exposure to
      terrorist acts. This exposure was associated with high PTS, depressive symptoms
      and alcohol use. Despite an apparently greater exposure to terrorism, religious
      adolescents reported lower levels of PTS and alcohol consumption, but similar
      levels of depressive symptoms to non-religious adolescents. Problem-solving
      coping predicted higher depressive symptoms for religious adolescents exposed to
      terrorism but not for similarly exposed non-religious adolescents. In contrast,
      emotion-focused coping predicted more alcohol consumption among highly exposed
      non-religious adolescents, while emotion-focused coping predicted more alcohol
      consumption among religious adolescents with low exposure. The overall findings
      suggest that religiosity may buffer the negative consequences of exposure in
      other ways than through coping or support.

PMID- 16290917
TI  - "It was a snap decision": parental and professional perspectives on the speed of
      decisions about participation in perinatal randomised controlled trials.
AB  - For some perinatal trials, parents can be asked to make important decisions about
      trial participation within limited timeframes in highly stressful circumstances.
      This qualitative study explores the pace of decision-making for 78 parents
      associated with one or more of four such trials in the UK. The themes associated
      with rapid decisions were concern for their baby, reactions to staff, and
      perceptions of the benefits and risks associated with the trial. Those who took
      longer to decide whether or not to participate often described similar emotions
      to those who made rapid decisions, but their slower decisions were because more
      time was available, they wanted further discussion or they found the decision
      particularly difficult. The majority of those who made rapid decisions felt that
      there were no risks associated with the trial in question, in contrast to the
      majority of those who made slower decisions who felt there were risks. The
      parents did not appear to view rapid decisions as problematic. Although there was
      evidence of parental vulnerability in each trial context, they largely felt that
      they acted swiftly and responsibly in the best interests of their child in
      accordance with the timeframes that were set for them.

PMID- 16290918
TI  - Doctor-patient interaction in a randomised controlled trial of decision-support
      tools.
AB  - In this paper, we draw on the analytic perspectives of ethnomethodology to
      explore doctor-patient encounters in an experimental trial of a complex
      intervention: an efficacy randomised controlled trial (RCT) of decision-support
      tools in the UK. We show how the experimental context in which these encounters
      take place pervades the interactions within them. We argue that two interactional
      orders were at work in the encounters that we observed: (i) the ceremonial order
      of the consultation and (ii) the assemblage of the decision-support tool trial.
      We demonstrate how doctors in the trial oscillate between positions as
      authoritative clinician and neutralistic decision-support tool-implementer, and
      patients move between positions as passive recipients of clinical knowledge and
      as active subjects required to render their experience as calculable in terms of
      the demands of the decision-support tools and the broader trial they are embedded
      in. We demonstrate how the RCT coordinates the world of the clinical environment
      and the world of experimental evidence.

PMID- 16290919
TI  - Lateral biases in assumptions of lighting position.
AB  - People presume that the light source in pictures comes from above, and there is
      some evidence that this phenomenon also demonstrates lateral biases. When
      investigators present multiple ambiguous stimuli or visually complex objects,
      people assume that the source of light is from above, and to the left. However,
      when single relatively simple stimuli are presented, this lateral bias is not
      readily observed. To investigate whether lateral bias is dependent on the number
      of stimuli presented, the present experiment employs a within-subjects design to
      present single spheres or pairs of spheres. Contrary to our expectations,
      leftward biases were exhibited in both the single-sphere condition and the paired
      spheres condition. Single spheres that were lit from the left were more likely to
      be judged as convex than comparable spheres lit from the right. Similarly, when
      pairs of laterally lit spheres were presented and participants were asked to
      judge which sphere appeared to be more convex, participants chose spheres lit
      from the left regardless of the angle of illumination. Collectively, these
      results suggest that there are lateral biases in assumptions of illumination
      position and that these biases do not depend on the number of stimuli being
      perceived at any given time.

PMID- 16290920
TI  - Response to comments on 'Cytogenetic effects in children treated with
      methylphenidate' by El-Zein et al.

PMID- 16290921
TI  - Ursodeoxycholic acid differentially affects three types of sphingomyelinase in
      human colon cancer Caco 2 cells.
AB  - We investigated the effects of UDCA on sphingomyelinase (SMase) in Caco 2 cells
      cultured in monolayer and polarized conditions. Alkaline SMase activity was high
      in polarized cells whereas, acid and neutral SMase activities were high in
      monolayer cells. In polarized cells, UDCA increased alkaline SMase expression and
      caspase 3 activity but had no effect on acid and neutral SMases. In monolayer
      cells, UDCA reduced both acid and neutral SMase activities, inhibited cell
      proliferation, but had little effect on alkaline SMase and caspase 3 activities.
      In conclusion, UDCA differentially affects SMase activity, cell proliferation,
      and apoptosis in colonic cells depending on the cell conditions.

PMID- 16290924
TI  - Mechanism of vagal nerve stimulation (VNS) anti-convulsant action.

PMID- 16290922
TI  - Lung tumors in 2 year old strain A/J mice exposed for 6 months to tobacco smoke.
AB  - Young adult strain A/J mice were exposed for 6 months in a whole-body inhalation
      chamber to a mixture of 89% sidestream and 11% mainstream cigarette smoke
      generated from Kentucky 1R4F research cigarettes. Chamber concentrations of smoke
      constituents were 158mg/m(3) of total suspended particulate matter (TSP). After
      an additional 4 months in air, some of the animals were killed. Lung tumor
      multiplicities in the smoke exposed animals were 1.8+/-0.2 versus 0.9+/-0.2 in
      controls. In animals kept beyond the age of 12 months, lung tumor multiplicities
      increased in both groups, but remained at all times twice the control values in
      the smoke exposed animals compared to controls (4.3+/-0.7 vs. 2.1+/-0.5 tumors
      per lung in 24 months old animals). Histopathology showed that, in 2 year old
      animals, still about 80% of tumors were of benign nature. No tumors were found in
      the nasal passages. It was concluded that tobacco smoke exposure not simply
      accelerates the development of lesions that eventually would have developed
      spontaneously, but induced de novo formation of lung tumors in A/J mice.

PMID- 16290925
TI  - Cancer is a functional repair tissue.
AB  - When a wound occurs, growth and repair genes (GR genes, such as oncogenes, proto
      oncogenes, etc.) in surrounding cells are activated and secretion of growth and
      repair factors (GR factors, such as growth, stem cell, and stimulating factors,
      etc.) is induced to heal the wound. However, if the wound is persistent due to
      chronic physical (radiation, electromagnetic field, trauma, particles, etc.),
      chemical (carcinogens, toxic chemicals, heavy metals etc.) or biological (aging,
      free radicals, inflammation, nutrient deficiency, bacteria and virus infections,
      stress, etc.) damage, amplification of GR gene activation in surrounding cells
      may lead to a clinical cancer. Based on the commonalities between cancer and
      wound healing, a new hypothesis of cancer is presented: malignancies are not
      passive mutated useless masses; rather, they are functional tissues produced by
      GR gene activation to secrete GR factors in an effort to heal persistent wounds
      in the body. Based on the hypothesis, current cancer treatments aimed at killing
      cancer cells only may be misguided. The logical extension of the hypothesis is
      that cancer treatment focused on wound healing by limiting causes of persistent
      wounds, providing repair cells, GR factors, and substrates required by repair
      cells may yield more fruitful results than treatments focused on killing cancer
      cells alone. Spontaneous regressions of cancer, although rare, may be successful
      examples of serendipitous spontaneous wound healing. Standard therapies aimed at
      killing cancer cells, should be limited to adjuvant status for limiting symptoms
      or buying time for completion of the wound healing process. Attempts to destroy
      cancer cells without healing underlying persistent wounds will allow for eventual
      recurrence.

PMID- 16290926
TI  - Jet lag and enhanced susceptibility to malaria.

PMID- 16290927
TI  - Employing ICA and SOM for spike sorting of multielectrode recordings from CNS.
AB  - For classification of action potential shapes in multineuron recordings, we
      present a spike sorting system employing independent component analysis (ICA) and
      an unsupervised artificial neural network (Kohonen's self-organizing map, SOM).
      We focus on how ICA in the first stage of the spike sorting system can be used to
      address specific problems arising in recordings using multielectrode arrays in
      the CNS. Using real data recorded from the pontine nuclei in rats and simulated
      data, we evaluate the performance of several ICA algorithms to remove cross-talk
      between electrodes using data from continuous recording (or simulation). When
      using cut-out data, the standard format of extracellular spike recordings, new
      problems emerge and robust algorithms are needed. We demonstrate that several ICA
      algorithms show a good performance on cut-out data from multielectrode array
      recordings (simulated and real data). In tetrode recordings the same neuron is
      purposely recorded by several electrodes simultaneously and we show, how
      independent component analysis can be used in this case to identify redundant
      information and hence to compress relevant information, improving subsequent
      clustering of a SOM.

PMID- 16290928
TI  - Beclomethasone dipropionate attenuates airways hyperresponsiveness to neurokinin
      A and histamine in asthma.
AB  - BACKGROUND: Inhaled corticosteroids (ICS) are the most effective anti
      inflammatory agents available for the treatment of asthma but they produce only
      modest effects on airway inflammation and non-specific bronchial
      hyperresponsiveness (BHR). However, little is known about the possibility that
      treatment with ICS might cause additional protection on BHR to inhaled
      tachykinins such as neurokinin A (NKA). OBJECTIVE: Therefore, we compared the
      effects of beclomethasone dipropionate (BDP) on the degree of BHR to inhaled
      histamine and NKA in a double-blind, controlled, cross-over study of asthmatic
      patients. METHODS: Patients attended the laboratory before and after each 6 weeks
      treatment period to undertake concentration-response studies with histamine and
      NKA. Bronchial responsiveness to both funs was expressed as the provocative
      concentration producing a 20% decrease in FEV(1) from baseline (PC(20)). RESULTS:
      BDP therapy attenuated the constrictor response to both agonists to a similar
      degree, their geometric mean (range) PC(20) values increasing from 0.47 (0.21
      1.41) mg/ml to 2.43 (0.51-4.50) mg/ml (P<0.01, post-salb vs. post-BDP treatment)
      and from 101.7 (27.3-356.1) microg/ml to 666.7 (151.5-1,000) microg/ml (P<0.01,
      post-salb vs. post-BDP treatment) for histamine and NKA, respectively.
      CONCLUSION: Airway responsiveness to histamine and NKA is reduced by BDP to the
      same extent. As a result of these findings, provocation with NKA is unlikely to
      provide additional useful information in the assessment of airway inflammation in
      asthma.

PMID- 16290929
TI  - 3D-QSAR studies on antitubercular thymidine monophosphate kinase inhibitors based
      on different alignment methods.
AB  - Three dimensional quantitative structure-activity relationship (3D-QSAR) studies
      were carried out on deoxythymidine monophosphate (dTMP) derivatives inhibiting
      thymidine monophosphate kinase (TMPK) in Mycobacterium tuberculosis. Molecular
      field analysis (MFA) models with three different alignment techniques, namely,
      least squares, pharmacophore based and receptor based methods were developed.
      Receptor based MFA model showed better results when compared with least squares
      and pharmacophore based models. The results help us to understand the nature of
      substituents required for activity and thereby provide guidelines to design novel
      and potent inhibitors as antitubercular agents.

PMID- 16290930
TI  - Phenolic P2/P3 core motif as thrombin inhibitors--design, synthesis, and X-ray co
      crystal structure.
AB  - Prototypical thrombin inhibitors were synthesized based on a trisubstituted
      phenol as a core motif. A naphthylsulfonamide analogue showed excellent
      antithrombin activity. An X-ray co-crystal structure showed the expected
      interactions.

PMID- 16290931
TI  - Analysis of anti-PDE3 activity of 2-morpholinochromone derivatives reveals
      multiple mechanisms of anti-platelet activity.
AB  - A series of synthetic 2-morpholinochromones have been evaluated as inhibitors of
      platelet phosphodiesterase, PDE3A. While previous assertions about the anti-PDE3
      activity of this class have been confirmed, in some cases the reported anti
      platelet activities clearly derive from a non-PDE3 regulated mechanism. The
      potential utility of 2-morpholinochromones either as PDE3 inhibitors and/or anti
      thrombotic agents thus remains only poorly examined.

PMID- 16290932
TI  - Phthalazinones 2: Optimisation and synthesis of novel potent inhibitors of
      poly(ADP-ribose)polymerase.
AB  - We have previously described the discovery of poly(ADP-ribose)polymerase-1 (PARP
      1) inhibitors based on a phthalazinone scaffold. Subsequent optimisation of
      inhibitory activity, metabolic stability and pharmacokinetic parameters has led
      to a novel series of meta-substituted 4-benzyl-2H-phthalazin-1-one PARP-1
      inhibitors which retain low nM cellular activity and show good stability in vivo
      and efficacy in cell based models.

PMID- 16290934
TI  - Highly potent and selective zwitterionic agonists of the delta-opioid receptor.
      Part 1.
AB  - A series of zwitterionic delta-opioid agonists, with targeted physicochemistry,
      as a strategy to limit potential for CNS exposure, were prepared. These agents
      were found to possess exquisite potency and selectivity over mu and kappa-opiate
      activity. Furthermore, analogue 3a was found to display restricted CNS exposure,
      as evidenced by its inactivity in a rodent hyperlocomotion assay of central
      opiate activity. Dog pharmacokinetic studies on 3a indicated encouraging oral
      bioavailability.

PMID- 16290933
TI  - Synthesis and biological evaluation of novel pyrrolo[2,1-c][1,4]benzodiazepine
      prodrugs for use in antibody-directed enzyme prodrug therapy.
AB  - The design, synthesis and evaluation of four novel pyrrolo[2,1
      c][1,4]benzodiazepine (PBD) prodrugs (1a,b and 2a,b; ) for potential use in
      carboxypeptidase G2 (CPG2)-based antibody-directed enzyme prodrug therapy (ADEPT)
      is reported. Although all four prodrugs were shown to be less cytotoxic than the
      released parent PBDs 3 and 4, the urea prodrugs 1b and 2b were found to be too
      unstable for use in ADEPT, whereas carbamates 1a and 2a are both stable in an
      aqueous environment and are good substrates for CPG2.

PMID- 16290935
TI  - Synthesis and structure-activity relationships of novel poly(ADP-ribose)
      polymerase-1 inhibitors.
AB  - A series of novel pyrrolocarbazoles was synthesized as potential PARP-1
      inhibitors. Pyrrolocarbazole 1 was identified as a potent PARP-1 inhibitor (IC50
      = 36 nM) from our internal database. Synthesis of analogs around this template
      with the aid of modeling studies led to the identification of the truncated imide
      14. Compound 14 (IC50 = 40 nM), with deleted B-ring, was found to be an
      equipotent PARP-1 inhibitor.

PMID- 16290936
TI  - Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde
      inhibitors?
AB  - Starting from potent aldehyde inhibitors with poor drug properties,
      derivatization to semicarbazones led to the identification of a series of
      semicarbazone-based cathepsin K inhibitors with greater solubility and better
      pharmacokinetic profiles than their parent aldehydes. Furthermore, a
      representative semicarbazone inhibitor attenuated bone resorption in an ex vivo
      rat calvarial bone resorption model. However, based on enzyme inhibition
      comparisons at neutral pH, semicarbazone hydrolysis rates, and 13C NMR
      experiments, these semicarbazones probably function as prodrugs of aldehydes.

PMID- 16290937
TI  - Audit of negative assessments in a breast-screening programme in women who later
      develop breast cancer-implications for survival.
AB  - The aim of this study was to examine observed short-term survival, to estimate
      future survival, and to assess the impact on survival of amending procedures to
      avoid false negatives in women recalled for further assessment due to a
      suspicious screening mammogram. From the start of screening in the seven centres
      in the East Anglian region, 1 April 1989 to 31 December 1999, 503493 women from a
      total population of 2.2 million were screened, 25346 were recalled for an
      assessment and 3689 were diagnosed with breast cancer. Of the 21657 women given a
      negative result at these assessments, 193 women were subsequently diagnosed with
      194 breast tumours at the site previously assessed. These women were followed up
      for survival, with survival analysis adjusting for host and tumour attributes. We
      also predicted long-term survival using the pathological features of the tumours
      diagnosed. From previous estimates of tumour progression rates, we estimated the
      reduction in incidence of advanced tumours and the potential saving of lives had
      unsatisfactory assessments been carried out within guidelines. There were 17
      deaths, 15 in women who had unsatisfactory assessments. Five-year survival was
      estimated at 93% (95% CI: 88-97%) for breast cancer and 91% (95% CI: 86-95%) for
      all cause deaths. Women with positive nodes and/or larger tumours had
      significantly worse survival. Twenty years survival for women with unsatisfactory
      assessments was estimated at 66% (35 deaths) and predicted a potential saving of
      7-9 lives (14-18% reduction in expected fatality within this special tumour
      population) had original assessments been carried out within current guidelines.
      This retrospective audit of a small and special tumour population shows a
      potential reduction in breast cancer deaths of 18%, had current guidelines been
      available for the original assessments. Increased use of percutaneous biopsy in
      recent years should address the problem.

PMID- 16290939
TI  - Bicyclic melatonin receptor agonists containing a ring-junction nitrogen:
      Synthesis, biological evaluation, and molecular modeling of the putative
      bioactive conformation.
AB  - Employing 1,3-dipolar cycloaddition for the synthesis of the 7a-azaindole
      nucleus, analogues of melatonin have been synthesized and tested against human
      and amphibian melatonin receptors. Introducing a phenyl substituent in position 2
      of the heterocyclic moiety significantly increased binding affinity to both the
      MT1 and MT2 receptors. Shifting the methoxy group from position 5 to 2 of the 7a
      azaindole ring led to a substantial reduction of MT1 binding when MT2 recognition
      was maintained. We theoretically investigated the hypothesis whether the 2
      methoxy function of the azamelatonin analogue 27 is able to mimic the 5-methoxy
      group of the neurohormone by directing its 2-methoxy function toward the methoxy
      binding site. DFT calculations and experimental binding differences of analogue
      compounds indicate that the energy gained by forming the methoxy-specific
      hydrogen-bond interaction should exceed the energy required for adopting an
      alternative conformation.

PMID- 16290938
TI  - Selective binding of coumarin enantiomers to human alpha1-acid glycoprotein
      genetic variants.
AB  - Coumarin-type anticoagulants, warfarin, phenprocoumon and acenocoumarol, were
      tested for their stereoselective binding to the human orosomucoid (ORM; AGP)
      genetic variants ORM 1 and ORM 2. Direct binding studies with racemic ligands
      were carried out by the ultrafiltration method; the concentrations of free
      enantiomers were determined by capillary electrophoresis. The binding of pure
      enantiomers was investigated with quinaldine red fluorescence displacement
      measurements. Our results demonstrated that all investigated compounds bind
      stronger to ORM 1 variant than to ORM 2. ORM 1 and human native AGP preferred the
      binding of (S)-enantiomers of warfarin and acenocoumarol, while no
      enantioselectivity was observed in phenprocoumon binding. Acenocoumarol possessed
      the highest enantioselectivity in AGP binding due to the weak binding of its (R)
      enantiomer. Furthermore, a new homology model of AGP was built and the models of
      ORM 1 and ORM 2 suggested that difference in binding to AGP genetic variants is
      caused by steric factors.

PMID- 16290940
TI  - Synthesis and dopamine receptor binding of sulfur-containing aporphines.
AB  - We investigated acid-catalyzed rearrangement of thebaine 14 and its N-propyl
      analog 15 with methanesulfonic acid in the presence of the nucleophiles
      methanethiol and hydrogen sulfide. R(-)-2-methylthioapocodeine 16, R(-)-2
      methylthioapomorphine 18, and their N-n-propyl analogs 17, 19 were obtained by
      rearrangement in the presence of methanethiol. However, with hydrogen sulfide,
      rearrangement of thebaine 14 and its N-n-propyl analog 15 produced sulfide-linked
      bis-aporphines 21-24 instead of expected R(-)-2-mercaptoapocodeines 12, 13 and R(
      )-2-mercaptoapomorphines 10, 11. R(-)-2-Methylthio-N-n-propylnorapomorphine 19
      had higher affinity (Ki = 3.7 nM) at D2 receptors in rat forebrain tissue than
      other novel 2-substituted sulfur-containing aporphines (Ki > or = 50 nM).
      Behavioral testing of the novel agents in rat indicated moderate locomotor
      arousal after systemic injection, and none after intragastric administration,
      indicating poor oral bioavailability.

PMID- 16290941
TI  - MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 5:
      Carbon-substituted analogues at the C-2 position.
AB  - A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, derivatized at the 2
      position with carbon-linked substituents, were synthesized and evaluated for
      their ability to potentiate the activity of the fluoroquinolone levofloxacin
      (LVFX) and the anti-pseudomonas beta-lactam aztreonam (AZT) in Pseudomonas
      aeruginosa. Palladium-catalyzed cross-coupling methods were applied for the
      incorporation of aliphatic and aromatic substituents.

PMID- 16290942
TI  - Sorption and complexation of Eu(III) on alumina: effects of pH, ionic strength,
      humic acid and chelating resin on kinetic dissociation study.
AB  - The effects of pH (pH=2-12), ionic strength (0.01-2 mol/l NaNO(3)) and humic acid
      on the sorption and complexation of Eu(III) on alumina were investigated by using
      batch techniques. The experiments were carried out at room temperature and under
      ambient conditions. The results indicate that the sorption of Eu(III) on alumina
      is strongly influenced by humic acid. The sorption of Eu(III) on alumina is
      significantly dependent on pH values and independent of ionic strength. The
      sorption of Eu(III) on alumina may be attributed to surface complexation. The
      species of Eu(III) on HA-alumina colloids is dominated by both HA and alumina,
      and the addition sequences of HA or Eu(III) to the ternary system do not
      influence the sorption of Eu(III) to HA-coated alumina. Kinetic dissociation of
      Eu(III) from bare and HA-coated alumina was also studied by using the chelating
      resin. The result was discussed by a pseudo-first-order kinetics model.

PMID- 16290944
TI  - Microfluidic reactor for the radiosynthesis of PET radiotracers.
AB  - Here we show the first application of a microfabricated reaction system to PET
      radiochemistry, we term "microfluidic PET". The short half-life of the positron
      emitting isotopes and the trace chemical quantities used in radiolabelling make
      PET radiochemistry amenable to miniaturisation. Microfluidic technologies are
      capable of controlling and transferring tiny quantities of liquids which allow
      chemical and biochemical assays to be integrated and carried out on a small
      scale. Such technologies provide distinct advantages over current methods of PET
      radiochemical synthesis. To demonstrate "proof of principle" we have investigated
      the radiohalogenation of small and large molecular weight molecules using the
      microfluidic device. These reactions involved the direct radioiodination of the
      apoptosis marker Annexin V using iodine-124, the indirect radioiodination of the
      anti-cancer drug doxorubicin from a tin-butyl precursor and the radiosynthesis of
      2-[(18)F]FDG from a mannose triflate precursor and fluorine-18 and hence provide
      a test bed for microfluidic reactions. We demonstrate the rapid radioiodination
      of the protein Annexin V (40% radiochemical yield within 1 min) and the rapid
      radiofluorination of 2-[(18)F]FDG (60% radiochemical yield within 4s) using a
      polymer microreactor chip. Chromatographic analysis showed that the labelling
      efficiency of the unoptimised microfluidic chip is comparable to conventional PET
      radiolabelling reactions.

PMID- 16290943
TI  - Preparation and characterization of Boron carbide nanoparticles for use as a
      novel agent in T cell-guided boron neutron capture therapy.
AB  - Boron carbide nanoparticles are proposed as a system for T cell-guided boron
      neutron capture therapy. Nanoparticles were produced by ball milling in various
      atmospheres of commercially available boron carbide. The physical and chemical
      properties of the particles were investigated using transmission electron
      microscopy, photon correlation spectroscopy, X-ray photoelectron spectroscopy, X
      ray diffraction, vibrational spectroscopy, gel electrophoresis and chemical
      assays and reveal profound changes in surface chemistry and structural
      characteristics. In vitro thermal neutron irradiation of B16 melanoma cells
      incubated with sub-100 nm nanoparticles (381.5 microg/g (10)B) induces complete
      cell death. The nanoparticles alone induce no toxicity.

PMID- 16290945
TI  - Radioactive byproducts in [18O]H2O used to produce 18F for [18F]FDG synthesis.
AB  - Potential radioactive byproducts in [(18)O]H(2)O irradiated with 9.6 MeV protons
      to produce (18)F were analyzed theoretically and experimentally. Twenty two
      nuclear reaction cross sections included in the National Nuclear Data Center's
      (NNDC) data base were selected from the possible nuclear reactions between 9.6
      MeV protons and a silver havar target. Ten radionuclides: (52)Mn, (55)Fe, (55)Co,
      (56)Co, (57)Co, (58)Co, (59)Ni, (95)Tc, (96)Tc and (109)Cd were detected
      experimentally in [(18)O]H(2)O by using high purity germanium semiconductor
      detectors. The activities of the 10 radionuclides were distributed between 4B q
      and 1.2k Bq. These activities were less than the reference values given in the
      International Basic Safety Standards. The radionuclides derived from nuclear
      reactions between a silver target body and 9.6 MeV protons at a beam current 25
      microA for 60 min irradiation would be exempt from restrictions for radioactive
      waste. The purified [(18)F]FDG prepared from (18)F produced by irradiating a
      silver havlar target with 9.6 MeV protons was not contaminated by the
      radionuclides.

PMID- 16290946
TI  - Analysis of metal radioisotope impurities generated in [(18)O]H(2)O during the
      cyclotron production of fluorine-18.
AB  - We show the separation of metal radioisotope impurities using capillary
      electrophoresis (CE). The methodology used is an improvement of existent
      protocols for separation of stable metal ions. Production of fluorine-18 using
      [(18)O]H(2)O-enriched water encased in a titanium target body results in the
      production of several metal radioisotope impurities. Optimisation of the
      conditions for CE separation of the metal radioisotope impurities incorporated
      the use of 6 mM 18-Crown-6 in combination with 12 mM glycolic acid as complexing
      agents within the running buffer (10 mM pyridine, pH 4.0). Using this optimised
      procedure, we were able to separate and detect a number of metal radioisotopes,
      including chromium, cobalt, manganese, vanadium and berillium, within the fM
      concentration range.

PMID- 16290948
TI  - Studies on the production and quality assurance of miniature (125)I radioactive
      sources suitable for treatment of ocular and prostate cancers.
AB  - (125)I sources were prepared by adsorption of (125)I on palladium-coated silver
      wires. The effect of reducing agent on percentage adsorption of (125)I was
      studied and the amount of adsorbed activity on source core was studied by
      repeated adsorption cycles. The activity per source in the sources produced from
      the same batch varied with coefficient of variation (i.e. the ratio of standard
      deviation to mean multiplied by 100) less than 10%. The unencapsulated source
      exhibited low leachability (< 0.01%). The laser parameters were optimized to
      obtain quality welds with negligible leak rate. The sources were laser
      encapsulated in titanium capsules of 0.8 mm (OD) x 4.5mm (l). The release of
      radioactivity from encapsulated sources in an immersion test at 50 degrees C for
      5 h was <5 nCi (185 Bq). The surface contamination on the sealed capsules was
      found to be<0.05 nCi or 1.85 Bq per source. The sources were used in the
      treatment of a child having retinoblastoma.

PMID- 16290947
TI  - Microfluidic technology for PET radiochemistry.
AB  - This paper describes the first application of a microfabricated reaction system
      to positron emission tomography (PET) radiochemistry. We have applied
      microfluidic technology to synthesise PET radiopharmaceuticals using (18)F and
      (124)I as labels for fluorodeoxyglucose (FDG) and Annexin-V, respectively. These
      reactions involved established methods of nucleophilic substitution on a mannose
      triflate precursor and direct iodination of the protein using iodogen as an
      oxidant. This has demonstrated a proof of principle of using microfluidic
      technology to radiochemical reactions involving low and high molecular weight
      compounds. Using microfluidic reactions, [(18)F]FDG was synthesised with a 50%
      incorporation of the available F-18 radioactivity in a very short time of 4s. The
      radiolabelling efficiency of (124)I Annexin-V was 40% after 1 min reaction time.
      Chromatographic analysis showed that such reaction yields are comparable to
      conventional methods, but in a much shorter time. The yields can be further
      improved with more optimisation of the microfluidic device itself and its fluid
      mixing profiles. This demonstrates the potential for this technology to have an
      impact on rapid and simpler radiopharmaceutical synthesis using short and medium
      half-life radionuclides.

PMID- 16290949
TI  - Sotalol and amiodarone versus digoxin for conversion of recent onset atrial
      fibrillation.

PMID- 16290951
TI  - Type 2 diabetes, dyslipidemia, and vascular risk: rationale and evidence for
      correcting the lipid imbalance.
AB  - Type 2 diabetes is an important cardiovascular risk factor. A significant
      component of the risk associated with type 2 diabetes is thought to be because of
      its characteristic lipid "triad" profile of raised small dense low-density
      lipoprotein levels, lowered high-density lipoprotein, and elevated triglycerides
      (TGs). Trials of statins and fibrates have included substantial numbers of
      patients with diabetes and indicate that lipid lowering reduces cardiovascular
      event rates in these patients. However, statins alone do not always address all
      the lipid abnormalities of diabetes. Fibrates, which have low affinity for
      peroxisome proliferator-activated receptor alpha (PPARalpha), improve most
      aspects of the atherogenic dyslipidemia of diabetes. Chronic elevations of free
      fatty acids (FFA) induce insulin resistance and contribute to the lipid triad of
      diabetes. Therefore, reducing their levels is likely to ameliorate insulin
      resistance and improve the lipid triad of diabetes. PPARs are intimately involved
      in the regulation of FFA: PPARalpha modulation increases FFA catabolism and
      PPARgamma agonism (eg, by thiazolidinediones) increases TG lipolysis, FFA
      transport, conversion of FFA to TGs, and safe storage of FFA. Integrating potent
      PPARalpha and PPARgamma activity may deliver greater improvement of the diabetic
      dyslipidemic profile and its attendant risks than selective PPAR activation.

PMID- 16290953
TI  - Noncompliance in cardiovascular clinical trials.

PMID- 16290952
TI  - Antidepressant therapy in patients with ischemic heart disease.
AB  - Depressive disorders are common in patients with ischemic heart disease and have
      serious consequences in terms of the risk of further cardiac events and cardiac
      mortality. Among survivors of acute myocardial infarction, up to one fifth meet
      diagnostic criteria for major depression, and the presence of major depression
      carries a >5-fold increased risk for cardiac mortality within 6 months. This
      article reviews clinical trial data on the cardiac safety profiles of
      antidepressant agents with the aim of discussing clinical considerations in
      selecting the most appropriate treatment of comorbid depression in patients with
      ischemic heart disease. Tricyclic antidepressants are effective against
      depression but are associated with cardiovascular side effects including
      orthostatic hypotension, slowed cardiac conduction, antiarrhythmic activity, and
      increased heart rate. Selective serotonin reuptake inhibitors, by contrast, have
      benign cardiovascular profiles and are well tolerated in patients with cardiac
      disease. The safety of dual-acting serotonin and noradrenaline reuptake
      inhibitors has not been well studied. Intervention with a selective serotonin
      reuptake inhibitors has the potential to provide the depressed patient with
      ischemic heart disease relief from their depressive symptoms and may offer a
      potential improvement in their cardiovascular risk profile.

PMID- 16290954
TI  - Design of a registry to characterize "real-world" outcomes of percutaneous
      coronary revascularization in the drug-eluting stent era.
AB  - BACKGROUND: Clinical trials have shown drug-eluting stents (DES) to be superior
      to bare metal stents (BMS) in preventing in-stent restenosis and target vessel
      revascularization. Although these results have ushered in a sea change in the
      practice of myocardial revascularization, important questions remain unanswered
      concerning rates of ischemic complications when DES are used in a broader
      population not represented in the clinical trials. STUDY DESIGN: The EVENT
      registry will include 7500 to 10,000 patients enrolled at approximately 60 sites
      across the United States. The intent of the registry is to characterize a
      population of consecutive patients undergoing percutaneous coronary intervention
      with stent deployment using BMS and DES in terms of processes and outcomes of
      care. A unique aspect of EVENT is the prospective assessment of rates of
      periprocedural myocardial infarction among all patients. These data will allow us
      to compare rates of periprocedural myocardial infarction and other ischemic
      complications between patients receiving DES and BMS. In addition, the EVENT
      registry will characterize temporal changes in the patterns of DES use and the
      relationship between any such changes and both short- and long-term outcomes.

PMID- 16290955
TI  - Testing new targets of therapy in advanced heart failure: the design and
      rationale of the Strategies for Tailoring Advanced Heart Failure Regimens in the
      Outpatient Setting: BRain NatrIuretic Peptide Versus the Clinical CongesTion
      ScorE (STARBRITE) trial.

PMID- 16290956
TI  - Targeted pharmacological reversal of electrical remodeling after cardioversion-
      rationale and design of the Flecainide Short-Long (Flec-SL) trial.
AB  - Persistent atrial fibrillation (AF) causes relevant mortality and cardiovascular
      and noncardiovascular morbidity. Therefore, maintenance of sinus rhythm is an
      important clinical goal, especially when the patient is symptomatic, despite the
      fact that current treatment strategies are not sufficient to completely prevent
      recurrent AF. In addition to underlying atrial disease that predisposes to AF, AF
      in itself induces structural and electrical adaptations ("electrical remodeling"
      and "structural remodeling"). Underlying disease processes and parts of
      structural remodeling are not always reversible. Electrical remodeling, in
      contrast, is reversed by a few weeks of maintenance of sinus rhythm under
      experimental conditions. This corresponds to the period when most of the
      recurrent episodes of AF occur after cardioversion. Antiarrhythmic drugs that
      prolong the atrial action potential can assist in the prevention of recurrent AF
      by promoting the reversal of electrical remodeling. Such drugs, which are
      currently used over long periods after cardioversion, may only be needed until
      the physiological action potential duration is restored, for example, during the
      first few weeks after cardioversion of persistent AF. This treatment concept that
      we call "targeted pharmacological reversal of electrical remodeling" would limit
      both cost and drug-induced side effects of antiarrhythmic drug therapy after
      cardioversion. The Flec-SL trial, ISECTN62728743, therefore tests the main
      hypothesis that targeted pharmacological reversal of electrical remodeling by
      short-term antiarrhythmic drug therapy for 4 weeks after cardioversion is not
      inferior to standard long-term antiarrhythmic drug therapy for the prevention of
      recurrent AF after cardioversion in a parallel group, randomized, multicenter,
      open, blinded end point analysis design. Based on its effectiveness and
      pharmacokinetic profile, flecainide is used to test the study hypothesis. The
      trial uses daily transtelephonic electrocardiographic monitoring for all patients
      and will be conducted within the German Atrial Fibrillation Competence NETwork
      (AFNET) to facilitate inclusion of patients from electrophysiologically oriented
      cardiology centers, ordinary hospitals, and office-based physicians.

PMID- 16290957
TI  - A randomized clinical trial of hospital-based, comprehensive cardiac
      rehabilitation versus usual care for patients with congestive heart failure,
      ischemic heart disease, or high risk of ischemic heart disease (the DANREHAB
      trial)--design, intervention, and population.
AB  - BACKGROUND: Current guidelines broadly recommend comprehensive cardiac
      rehabilitation (CR), although evidence for this is still limited. It is not known
      whether evidence from before 1995 is still valid. STUDY DESIGN: The DANish
      Cardiac ReHABilitation (DANREHAB) trial was designed as a centrally randomized
      clinical trial to clarify whether hospital-based comprehensive CR is superior to
      usual care for patients with congestive heart failure, ischemic heart disease, or
      high risk for ischemic heart disease. A combined primary outcome measure included
      total mortality, myocardial infarction, or readmissions due to heart disease
      based on linkage to public registries. The CR was an individually tailored,
      multidisciplinary program (6 weeks of intensive CR and 12 months of follow-up)
      including patient education, exercise training, dietary counseling, smoking
      cessation, psychosocial support, risk factor management, and clinical assessment.
      STUDY POPULATION: Of 5060 discharged patients, 1614 (32%) were eligible for the
      trial and 770 patients were randomized (47% of those eligible). Participants were
      younger (P < .001) and had less comorbidity than nonparticipants (P < .03).
      CONCLUSION: Our trial shows that a large-scale, centrally randomized clinical
      trial on comprehensive CR can be conducted among a broadly defined patient group,
      but reaching the stipulated number of 1800 patients was difficult. Although the
      study included relatively many women and older people, elderly patients and
      patients with high comorbidity were underrepresented, which may influence the
      external validity.

PMID- 16290958
TI  - Global inflammation predicts cardiovascular risk in women: a report from the
      Women's Ischemia Syndrome Evaluation (WISE) study.
AB  - BACKGROUND: Measurement of C-reactive protein (CRP), a marker of inflammation, is
      recommended to improve cardiovascular disease (CVD) risk stratification. However,
      no studies have collectively evaluated how inflammatory markers cluster
      empirically and relate to angiographic coronary artery disease and CVD events.
      METHODS: From the WISE study, 580 women with fasting plasma samples of
      inflammatory markers (interleukin [IL]-6, IL-18, tumor necrosis factor alpha,
      transforming growth factor beta, CRP, serum amyloid A [SAA], and intercellular
      adhesion molecules) were analyzed over a median of 4.7 years follow-up. All women
      were referred for coronary angiography (1996-2000) to evaluate suspected
      myocardial ischemia. RESULTS: In factor analysis, a "proinflammation" factor
      (cluster) loaded on IL-6, CRP, and SAA (r = 0.63-0.87); a "proinflammation and
      anti-inflammation" cluster loaded on IL-18 and tumor necrosis factor alpha (r =
      0.72, 0.77); and an "immunosuppressive" factor loaded singly on transforming
      growth factor beta (r = 0.96). No cluster was independently associated with
      angiographic coronary artery disease. However, quartile increases of the
      "proinflammation" cluster (IL-6, CRP, and SAA) yielded death rates of 2.6%, 7.2%,
      13.1%, 26.6%, respectively (P < .0001). Women with > or = 2 of 3 proinflammation
      markers in the upper quartile had an adjusted relative risk of death of 4.21 (95%
      CI 1.91-9.25), a higher conferred risk than any single marker alone, all of which
      were roughly equally predictive. CONCLUSIONS: Although IL-6, CRP, and SAA all
      predict CVD risk in women, development of global measures of inflammation and
      simply counting the number of markers with high levels improve CVD risk
      stratification. In addition, results indicate that the adverse impact of
      inflammation may be largely through other mechanisms than promotion of
      atherogenesis (ie, destabilization of vulnerable plaques).

PMID- 16290959
TI  - Hormone therapy, C-reactive protein, and progression of atherosclerosis: data
      from the Estrogen Replacement on Progression of Coronary Artery Atherosclerosis
      (ERA) trial.
AB  - OBJECTIVE: To compare the effects of estrogen and estrogen plus progestin on
      levels of C-reactive protein (CRP) and interleukin-6 (IL-6), and to examine the
      relationship between these changes and progression of angiographically defined
      coronary disease. METHODS: Baseline and follow-up (year 1 and year 3) plasma
      levels of IL-6 and CRP were measured in a subset of 232 patients from the
      Estrogen Replacement in Atherosclerosis (ERA) trial. RESULTS: Serial angiograms
      were also available at baseline and closeout. Estrogen alone increased CRP by 40%
      (P = .01) at 1 year and 38% P = .002) at closeout. Estrogen plus
      medroxyprogesterone acetate increased CRP by 44.7% P = .001) at 1 year and 54.7%
      P = .0001) at closeout as compared with baseline levels. There were no
      significant changes in IL-6 with either treatment. In women in the active
      treatment arm, change in CRP during the first year was not associated with
      progression of coronary disease P = .2). CONCLUSIONS: Estrogen and estrogen plus
      medroxyprogesterone significantly raise CRP levels in women with established
      coronary disease. In contrast, IL-6 levels are not affected by estrogen or
      estrogen plus progestin. Estrogen-induced changes in CRP are not associated with
      progression of atherosclerosis.

PMID- 16290960
TI  - Diabetes status and racial differences in post-myocardial infarction mortality.
AB  - BACKGROUND: Prior studies regarding the effect of racial status on post
      myocardial infarction (MI) in subjects with diabetes have yielded conflicting
      results. We evaluated the effect of diabetes status on racial differences in post
      MI mortality and morbidity for a 7-year period, from 1990 through 1997. METHODS:
      All patients discharged with the primary diagnosis of acute MI from any Veterans
      Affairs Medical Center in the country between October 1990 and September 1997
      were identified. Demographic, comorbid conditions, inpatient, outpatient,
      mortality, and readmission data were extracted. Mortality, revascularization,
      readmissions, and length of hospital stay for MI were compared for the group with
      diabetes and that without diabetes. Comparison was made between black and white
      patients. Independent predictors of survival using a Cox regression model were
      examined. RESULTS: We identified 67,889 patients with MI of whom 17,756 (26%) had
      diabetes. Race status was known for 66,506 subjects of whom 55,731 (84%) were
      white and 8437 (13%) were black. Regardless of the race, the diabetic patients
      tended to have higher mortality than nondiabetic patients. The post-MI mortality
      during the entire follow-up period tended to be similar between blacks and whites
      for the nondiabetic patients, whereas the mortality tended to be lower in blacks
      than in whites in diabetic patients. CONCLUSIONS: Mortality from post-MI is
      significantly lower in blacks with diabetes than in whites with diabetes. In
      contrast, no racial difference in long-term mortality was seen among subjects
      without diabetes. Thus, it appears that diabetes status determines racial
      variation in post-MI mortality. The reasons for better survival post-MI of blacks
      in general and among subjects with diabetes in particular need to be further
      investigated.

PMID- 16290961
TI  - Effects of canrenoate plus angiotensin-converting enzyme inhibitors versus
      angiotensin-converting enzyme inhibitors alone on systolic and diastolic function
      in patients with acute anterior myocardial infarction.
AB  - BACKGROUND: Aldosterone (ALDO) exerts profibrotic effects, acting via the
      mineralocorticoid receptors in cardiovascular tissues. Aldosterone antagonism in
      combination with angiotensin-converting enzyme inhibition may better protect
      against the untoward effects of ALDO than angiotensin-converting enzyme
      inhibition alone. METHODS: In a double-blind randomized study, the tolerability
      and efficacy of canrenoate (25 mg/d) plus captopril versus captopril alone were
      evaluated in 510 patients with an acute anterior myocardial infarction (MI), a
      serum creatinine concentration < 2.0 mg/dL, and a serum potassium level < 5.0
      mmol/L. Three hundred forty-one patients received captopril and 25-mg canrenoate
      (group A). Group B (346 patients) received captopril and placebo. At baseline and
      at 10, 90, and 180 days after admission, Doppler echocardiography was performed.
      RESULTS: Clinical and demographic aspects were similar in both groups. In
      addition, baseline cardiac enzyme levels, left ventricular function, and
      incidence of surgical interventions and angioplasty were comparable. Overall,
      creatinine, blood urea, and serum potassium levels did not show significant
      differences between groups. However, in 18 patients in group A, increases in
      serum potassium levels to > 5.5 mEq/L and creatinine levels to > 2.0 mg/L after
      10 days of treatment were observed. At 180 days, the mitral E-wave-A-wave ratio
      was higher (P = .0001) and left ventricular end-systolic volume was smaller (P =
      .0001) in patients treated with canrenoate than in those receiving placebo. No
      further side effects were observed during the study period. CONCLUSIONS: Our data
      suggest that the combination of captopril plus canrenoate is well tolerated after
      an acute MI and has beneficial effect on systolic and diastolic parameters and
      may decrease post-MI remodeling.

PMID- 16290962
TI  - Size and transmural extent of first-time reperfused myocardial infarction
      assessed by cardiac magnetic resonance can be estimated by 12-lead
      electrocardiogram.
AB  - BACKGROUND: The ability of the 12-lead electrocardiogram (ECG) to quantify size
      and transmural extent of myocardial infarction (MI) is not fully explored. Q
      waves are still thought of as indicative of transmural MI despite that several
      studies have rejected this association. We hypothesized that size and transmural
      extent of acute MI indeed can be estimated by QRS scoring on the 12-lead ECG
      using delayed, contrast-enhanced magnetic resonance imaging (DE-MRI) as gold
      standard and that Q waves are not predictive of transmural MI. METHODS: Twenty
      nine patients with first-time reperfused MI were studied. Delayed, contrast
      enhanced magnetic resonance imaging was performed and 12-lead ECG was recorded 8
      +/- 1 days after the acute event. Myocardial infarction size and transmurality
      were determined by DE-MRI and compared with Selvester QRS score from the ECG
      recorded on the same day. RESULTS: There was a good correlation (r = 0.79, P <
      .001) between MI size by QRS scoring and DE-MRI. As local MI transmurality
      increased as assessed by DE-MRI, the local QRS score increased progressively (P <
      .001). There was no significant difference in the number of Q-wave-related QRS
      points between nontransmural and transmural MI (1.8 +/- 0.6 vs 2.9 +/- 0.4, P =
      .14). The global QRS score, however, differed significantly (3.1 +/- 0.8 vs 5.1
      +/- 0.6, P < .05). CONCLUSION: QRS score is significantly related to both MI size
      and transmurality by DE-MRI in patients with first-time reperfused MI. Presence
      of Q waves, however, is not indicative of transmural MI in these patients. Thus,
      QRS scoring could potentially be used for diagnosing and characterizing MI in
      patients with suspected recent MI.

PMID- 16290963
TI  - Applicability of clinical prediction models in acute myocardial infarction: a
      comparison of traditional and empirical Bayes adjustment methods.
AB  - INTRODUCTION: Several clinical prediction models have been developed to predict
      outcome after acute myocardial infarction. Updating to local circumstances may be
      required to make such models better applicable. We aimed to compare traditional
      and empirical Bayes (EB) methods to perform such updating. METHODS: We focused on
      16 geographical regions within the GUSTO-I trial, which included 40,830 patients
      with acute myocardial infarction; of whom, 2851 (7.0%) had died by 30 days.
      Differences in mortality between regions were studied with traditional adjustment
      for case mix in logistic regression models and with EB methods. These methods
      updated predictions for new patients while accounting for the uncertainty in the
      traditionally estimated mortality differences. RESULTS: The case mix in the
      regions differed with respect to important predictive characteristics such as
      age, presence of shock, and anterior infarct location (all P < .001). These
      differences did not explain regional differences in 30-day mortality, which
      varied between 80% and 120% with traditional analyses (P < .01). The EB estimates
      for regional differences were much smaller (between 93% and 107%). CONCLUSIONS:
      Statistically significant differences in case mix and 30-day mortality were noted
      between geographical regions. The practical implications of this heterogeneity
      were, however, limited when model predictions were updated with EB methods.

PMID- 16290964
TI  - Cocaine and coronary calcification in young adults: the Coronary Artery Risk
      Development in Young Adults (CARDIA) Study.
AB  - BACKGROUND: Cocaine use is associated with myocardial ischemia and infarction,
      but it is unclear whether this is only because of the acute effects of cocaine on
      heart rate, blood pressure, and vasomotor tone or whether accelerated
      atherosclerosis from long-term exposure to cocaine also contributes. METHODS: We
      sought to measure the association between cocaine exposure and coronary
      calcification, a marker for atherosclerosis, among participants in the CARDIA
      Study who received computed tomography scanning and answered questions about
      illicit drug use at the year 15 examination in 2000-2001. RESULTS: Among 3038
      CARDIA participants (age 33-45 years, 55% women and 45% black), past cocaine
      exposure was reported by 35% and was more common among men, smokers, drinkers,
      and participants with less education. Powdered cocaine exposure was more common
      among whites, crack cocaine among blacks. Before adjustment, cocaine exposure was
      strongly associated with coronary calcification. After adjusting for age, sex,
      ethnicity, socioeconomic status, family history, and habits, however, these
      associations disappeared: adjusted odds ratios for coronary calcification were
      0.9 (95% CI 0.6-1.3) for 1 to 10, 1.2 (95% CI 0.8-1.7) for 11 to 99, and 1.0 (95%
      CI 0.6-1.6) for > or =100 lifetime episodes of cocaine use, in comparison with
      none. Sex, tobacco, and alcohol use appeared to be primarily responsible for the
      confounding we observed in unadjusted models. CONCLUSION: We found no evidence of
      a causal relationship between long-term exposure to cocaine and coronary
      calcification and conclude that acute nonatherogenic mechanisms probably explain
      most cocaine-associated myocardial infarction.

PMID- 16290965
TI  - Predictors of cardiopulmonary resuscitation and automated external defibrillator
      skill retention.
AB  - BACKGROUND: Few data exist regarding the retention of cardiopulmonary
      resuscitation (CPR) and automated external defibrillator (AED) skills over time
      in relationship to characteristics of lay volunteer responders, training, or risk
      of exposure to victims. The purpose of this study was to describe the
      characteristics associated with adequate CPR and AED skill retention. METHODS AND
      RESULTS: Skill retention was tested 3 to 18 months (mean 6.9 +/- 3.5 months)
      after initial training. Instructors judged adequacy of performance of essential
      CPR or AED skills and provided an overall assessment (adequate/inadequate), which
      was used as the outcome. Data on 7261 laypersons trained in CPR (4358 also
      received AED training) in 24 sites across the United States and Canada were
      available from the Public Access Defibrillation (PAD) Trial. Characteristics of
      the volunteers, classes, and facilities were evaluated as predictors of
      performance adequacy. Adjusting for site, intervention assignment (CPR-only or
      CPR + AED), and time since initial training, volunteer characteristics associated
      with adequate CPR performance were age (OR 0.78 per 10-year increment), male sex
      (OR 1.44), minority (OR 0.62), married (OR 1.35), prior emergency experience (OR
      1.66), prior CPR class (OR 1.68), prior advanced training (OR 1.59), and
      extracurricular CPR training (OR 1.91) (all P < .05). Characteristics associated
      with AED performance included age (OR 0.69), college education (OR 1.34), and
      native language other than English (OR 0.51) (all P < .05). CONCLUSIONS: Certain
      subgroups of lay volunteers may need targeted outreach programs in CPR and AED
      use, classes with longer training time, more practice, or more intense retraining
      to maintain their CPR and/or AED skills.

PMID- 16290966
TI  - A pilot study: the Noninvasive Surface Cooling Thermoregulatory System for Mild
      Hypothermia Induction in Acute Myocardial Infarction (the NICAMI Study).
AB  - BACKGROUND: Hypothermia reduces metabolic demands, limits reperfusion injury, and
      helps salvage the injured myocardium during ST-elevation myocardial infarction
      (STEMI). The aim of this study was to assess early induction of noninvasive mild
      hypothermia in patients with acute myocardial infarction undergoing primary
      percutaneous coronary intervention (PCI). METHODS: This was a safety and
      feasibility study of the Medivance Arctic Sun noninvasive thermoregulatory system
      (Medivance Inc, Louisville, Colo), used as adjunctive therapy in patients with
      first-time STEMI. Cooling was initiated by circulating chilled water through the
      Arctic Sun Energy Transfer Pads placed on the patient before primary PCI. Target
      temperature was 34.5 degrees C, maintained during 3 hours. Shivering was
      controlled with intravenous meperidine, and meperidine-related nausea was
      prevented with intravenous ondansetron. RESULTS: Nine patients underwent
      successful noninvasive surface cooling. All patients were Killip class I with a
      mean age of 62 years (8/9 males). Successful primary stenting was performed in
      all patients with glycoprotein inhibitors administered in 6 of 9 cases. Mean
      cooling time from induction to target temperature was 79 minutes (49 minutes in
      the last 4 enrolled cases). Mean total cooling duration was 267 minutes. Mean
      peak troponin T was 5.81 microg/L. Final TIMI flow grade 3 and final TIMI
      perfusion grade 3 were achieved in 9 of 9 patients and in 3 of 9 patients,
      respectively. Mean infarct size (by Myoview single photon emission computed
      tomography scans) was 23%. No hemodynamic or arrhythmic instability were
      documented. CONCLUSION: Mild hypothermia can be safely induced with noninvasive
      surface cooling in patients with STEMI undergoing primary PCI, allowing earlier
      myocardial protection before mechanical reperfusion therapy.

PMID- 16290967
TI  - Indinavir impairs endothelial function in healthy HIV-negative men.
AB  - BACKGROUND: Potent antiretroviral treatment has drastically reduced mortality in
      HIV-infected patients but may accelerate atherosclerotic disease, which could be
      partially mediated via endothelial dysfunction. METHODS: In 8 HIV-negative
      healthy males, leg blood flow responses to intraartery infusions of methacholine
      chloride (Mch), sodium nitroprusside, and NG-mono-methyl-L-arginine (L-NMMA) were
      measured before and after 4 weeks of daily oral indinavir. In the same subjects,
      we also assessed the effect of indinavir on lipids, insulin sensitivity, markers
      of inflammation, as well as oxidative stress. RESULTS: After 4 weeks of
      indinavir, the endothelium-dependent response to methacholine chloride was
      impaired (195% +/- 38% vs 83% +/- 13%, P < .05), the response to NG-mono-methyl-L
      arginine (nitric oxide-dependent tone) was nearly abrogated (-30% +/- 4% vs -1%
      +/- 11%, P < .05), whereas the endothelium-independent response to sodium
      nitroprusside remained unchanged. Fasting insulin levels increased from 5.8 +/-
      1.2 to 7.0 +/- 1.4 microU/mL (P < .05), and HOMA-IR scores increased from 1.3 +/-
      0.3 to 1.6 +/- 0.3 U (P < .05). There were no changes in blood pressure, lipids,
      markers of inflammation, or oxidative stress. CONCLUSIONS: Four weeks of the HIV
      1 protease inhibitor indinavir, in the absence of HIV-1 infection, causes
      vascular dysfunction most likely at the level of endothelial nitric oxide
      production. The vascular dysfunction may be mediated partially by the concomitant
      induction of insulin resistance but other mechanisms cannot be ruled out.

PMID- 16290968
TI  - Sex differences in left ventricular function in older persons with mild
      hypertension.
AB  - BACKGROUND: Epidemiologic studies suggest that women are at increased risk of
      developing heart failure secondary to hypertension. Other studies have documented
      sex differences in left ventricular systolic and diastolic function in the
      presence of pressure overload states such as seen in aortic stenosis and
      hypertension. It is less clear if sex differences are present among older persons
      with mild hypertension. METHODS: One hundred seven healthy subjects, aged 55 to
      75 years, with blood pressures ranging from 130 to 159 mm Hg systolic and/or 85
      to 99 mm Hg diastolic, were examined by standard echocardiography and the newer
      modalities of tissue Doppler and color M-mode imaging. RESULTS: Women had a lower
      peak mitral annular systolic velocity (Sm), 8.9 (95% CI 8.4-9.5) cm/s versus 10.2
      (95% CI 9.6-11.0) cm/s, (P < .01) than men. Among women, increasing age was
      associated with a reduction in diastolic function. For every decade of age, peak
      early mitral annular diastolic velocity (Em) declined by 1.6 cm/s (P < .01),
      mitral inflow velocity of propagation (Vp) declined by 26% (P < .01), E/Vp ratio
      increased by 20% (P = .03), and E/Em ratio increased by 11% (P = .04) in women.
      No age-associated changes were seen in men. CONCLUSIONS: As revealed by newer
      echocardiographic imaging modalities, women with mild hypertension showed greater
      reductions in systolic and diastolic function as they aged compared with men. Our
      findings are consistent with the increased risk older women have of developing
      heart failure because of hypertension.

PMID- 16290969
TI  - Oxygen pulse during exercise is related to resting systolic and diastolic left
      ventricular function in older persons with mild hypertension.
AB  - BACKGROUND: The mechanisms responsible for impaired cardiovascular hemodynamics
      during exercise among persons with milder forms of hypertension are not well
      documented. We examined the relationship of oxygen pulse during exercise, a
      correlate of stroke volume, with echocardiographic indices of resting left
      ventricular function to determine whether abnormal contractility and relaxation
      are related to abnormal cardiovascular dynamics during exercise among such
      persons. METHODS: Subjects were 44 men and 55 women ages 55 to 75 years with mild
      hypertension but who were otherwise healthy. Resting left ventricular systolic
      and diastolic functions were assessed with 2-dimensional Doppler echocardiography
      and tissue Doppler imaging. Oxygen pulse (millimeters per beat) at rest and
      during multistage treadmill testing was derived from measurements of oxygen
      consumption and heart rate. The slope of oxygen pulse between successive exercise
      stages was calculated. RESULTS: After a steep rise in oxygen pulse from rest to
      stage 1 of exercise, a markedly diminished oxygen pulse slope was seen between
      subsequent exercise stages. In stepwise regression analysis, the increase in the
      slope of oxygen pulse from rest to stage 1 was explained by a greater lean body
      mass (57%, P < .001) and a larger left atrial size (2%, P < .001). After exercise
      stage 1, the increase in the slope of oxygen pulse was explained by sex (24%, P <
      .001), higher mitral E/A ratio (6%, P < .001), and higher mitral annular systolic
      velocity (6%, P < .001). CONCLUSIONS: These results suggest that a blunted oxygen
      pulse response to exercise among older persons with milder forms of hypertension
      may reflect impaired left ventricular stroke volume changes during exercise
      secondary to subtle abnormalities in both systolic and diastolic left ventricular
      functions.

PMID- 16290971
TI  - Impact of implantable cardioverter defibrillators on survival and recurrent
      hospitalization in advanced heart failure.
AB  - BACKGROUND: Although implantable cardioverter defibrillators (ICDs) are
      increasingly used in advanced (class III/IV) heart failure, their benefits may be
      limited by death from pump failure and data are limited. The aim of this study
      was to assess the impact of QRS duration and disease etiology on survival and
      rehospitalization in advanced heart failure patients with ICDs. METHODS: A
      retrospective study of 438 patients with heart failure (age 56 +/- 15, ejection
      fraction 29 +/- 15, 76% class III/IV) discharged between 1996 and 2000 was
      performed. RESULTS: An ICD was placed in 94 of the 438 patients for nonsustained
      (51.1%) or sustained (24.4%) ventricular arrhythmia, syncope (16.0%), or
      prophylaxis (8.5%). Patients with ICDs had a lower mean baseline ejection
      fraction (25% vs 30%, P = .007) but a trend toward fewer class IV symptoms (33%
      vs 44%, P = .164). Patients with ICDs had better survival (RR 0.48, P = .001) but
      increased rehospitalization (RR 1.41, P = .031). In both the ischemic and
      nonischemic subgroups, survival was superior in patients with ICDs (RR 0.38, P =
      .003 and RR 0.54, P = .042). Patients with QRS < 120 milliseconds had a trend
      toward better survival with an ICD (RR 0.42, P = .119) but increased
      rehospitalization (RR 2.13, P = .021). Patients with QRS > or = 120 milliseconds
      had better survival with an ICD (RR 0.45, P = .001) without increased risk of
      rehospitalization (RR 1.22, P = .314). CONCLUSIONS: Patients with advanced heart
      failure selected to receive ICDs have better survival trends but shorter time to
      rehospitalization than patients without ICDs. Benefit appears greater for those
      with prolonged QRS duration.

PMID- 16290970
TI  - The Italian Registry for hypertrophic cardiomyopathy: a nationwide survey.
AB  - BACKGROUND: National registries are advocated as instrumental to the solution of
      rarity-related problems for patients with hypertrophic cardiomyopathy (HCM),
      including limited access to advanced treatment options. Thus, an Italian Registry
      for HCM was created to assess the clinical profile and the level of care
      nationwide of patients with HCM. METHODS: Cardiology centers over the national
      territory were recruited to provide clinical data of all patients with HCM ever
      seen at each institution. The enrollment period was from May 2000 to May 2002.
      RESULTS: The registry enrolled 1677 patients from 40 institutions. Most (69%)
      were followed at referral centers, whereas 31% were from community centers with
      intermediate-low patient flow. Patients diagnosed after routine medical
      examinations or familial screenings were 39%. Most patients were male (62%), in
      their fourth to sixth decade of life, and in New York Heart Association class I
      to II (89%); 24% had resting left ventricular obstruction and 18% had atrial
      fibrillation. During a 9.7-year average follow-up, cardiovascular mortality was
      1%/y, mostly because of heart failure, with no significant change over the last 3
      decades; sudden death was less common (0.4%/y). Only 4% of patients received a
      defibrillator; 14% of the 401 patients with LV outflow obstruction underwent
      invasive relief of obstruction; and <1% were offered genetic analyses or
      counseling. CONCLUSIONS: The Italian Registry represents the first comprehensive
      attempt to evaluate the clinical impact and management of HCM at a national
      level. Findings underscore the role of screening strategies for an early
      diagnosis and suggest limited use of the advanced therapeutic options for HCM.

PMID- 16290972
TI  - Depression predicts mortality and hospitalization in patients with myocardial
      infarction complicated by heart failure.
AB  - BACKGROUND: To evaluate whether depressive symptoms are independently predictive
      of mortality and hospitalization among patients with acute myocardial infarction
      (AMI) complicated by heart failure. METHODS: The EPHESUS trial enrolled patients
      with AMI complicated by heart failure. Patients from Canada, the UK, and the
      United States completed a Medical Outcomes Study-Depression questionnaire at
      baseline in addition to a comprehensive clinical examination. Cox proportional
      hazards regression was used to determine the relationship between depressive
      symptoms and outcomes, including 2-year all-cause mortality and cardiovascular
      death or hospitalization, adjusting for baseline clinical variables. RESULTS:
      Overall, 143 of 634 patients (22.6%) had significant depressive symptoms at
      baseline (Medical Outcomes Study-Depression score > or = 0.06). Depressed
      patients had higher 2-year mortality (29% vs 18%; P = .004) and cardiovascular
      death or hospitalization (42% vs 33%; P = .016). After risk adjustment,
      depressive symptoms remained significantly associated with mortality (hazard
      ratio 1.75, 95% CI 1.15-2.68, P = .01) and cardiovascular death or
      hospitalization (hazard ratio 1.41, 95% CI 1.03-1.93, P = .03). Results were
      consistent across demographic and clinical subgroups. CONCLUSIONS: Depression is
      an independent predictor of all-cause mortality and cardiovascular death or
      hospitalization after AMI complicated by heart failure. Although many factors may
      mediate outcomes in patients with AMI, studies are warranted to evaluate whether
      a depression intervention can improve survival and/or reduce hospitalizations.

PMID- 16290973
TI  - Racial differences in outcome and treatment effect in congestive heart failure.
AB  - BACKGROUND: In congestive heart failure (CHF), it is unknown whether race affects
      mortality and whether the effect of treatments differs by race. METHODS: This
      study was a post hoc analysis of data from the DIG study that evaluated the
      effect of digoxin on morbidity and mortality in CHF. RESULTS: Investigators
      followed 897 black and 6660 white participants for a mean of 37 months. Compared
      with whites, blacks were younger (60 +/- 13 vs 65 +/- 11 years). Total mortality
      was 34.2% in blacks and 33.6% in whites; hospitalization for worsening CHF
      occurred in 39% of blacks and 28% of whites. Cox regressions with race as the
      only covariate showed no effect of race on risk for death (relative risk = 1.04,
      95% CI 0.93-1.18, P = .49) but an increase in CHF hospitalization in blacks
      (relative risk = 1.52, 95% CI 1.35-1.70, P = .0001). Multivariate Cox regression
      showed no difference by race in risk for death or death/hospitalization for CHF
      and no difference in the effect of digoxin on either end point. CONCLUSION: Race
      is not an independent predictor of mortality in CHF. The effect of digoxin on
      morbidity and mortality in CHF does not differ in blacks and whites.

PMID- 16290974
TI  - Diastolic dysfunction after mediastinal irradiation.
AB  - BACKGROUND: Mediastinal irradiation is known to cause cardiac disease, but its
      effect on left ventricular diastolic function is unknown. The purpose of this
      study was to determine the prevalence of diastolic dysfunction and its
      association with prognosis in asymptomatic patients after mediastinal
      irradiation. METHODS: We recruited 294 patients who had received at least 35 Gy
      to the mediastinum for treatment of Hodgkin disease. Each patient underwent
      resting echocardiography, stress echocardiography, and nuclear scintigraphy.
      Survival free from cardiac events was determined during 3.2 years of follow-up.
      RESULTS: The mean age of the included patients was 42 years, and 49% were male.
      Adequate measurements of diastolic function were obtained in 282 (97%) patients.
      Diastolic dysfunction was considered mild in 26 (9%) and moderate in 14 (5%).
      Exercise-induced ischemia was more common in patients with diastolic dysfunction
      (23%) than those with normal diastolic function (11%, P = .008). After adjustment
      for patient demographics, clinical characteristics, and radiation history,
      patients with diastolic dysfunction had worse event-free survival than patients
      with normal function (hazard ratio 1.66, 95% CI 1.06-2.4). CONCLUSIONS: There is
      a high prevalence of diastolic dysfunction in asymptomatic patients after
      mediastinal irradiation, and the presence of diastolic dysfunction is associated
      with stress-induced ischemia and a worse prognosis. Screening with Doppler
      echocardiography may be helpful in identifying patients at risk for subsequent
      cardiac events.

PMID- 16290975
TI  - Pilot study to determine the impact of a multidisciplinary educational
      intervention in patients hospitalized with heart failure.
AB  - BACKGROUND: Patients with heart failure (HF) face challenges complying with
      multidrug regimens. OBJECTIVES: To examine the impact of a compliance enhancing
      intervention on medication compliance and morbidity in HF. DESIGN: Patients were
      randomized to either usual care or an inhospital educational intervention
      delivered by a multidisciplinary team (Intervention). SETTING: Acute medical and
      surgical units at a teaching hospital. PATIENTS: One hundred thirty four patients
      with a clinical diagnosis of HF and a left ventricular ejection fraction of < 40%
      requiring long-term medical treatment. MAIN OUTCOME MEASURES: A validated HF
      specific instrument provided a measure of knowledge. We characterized patients as
      noncompliant if pharmacy refill data suggested they had taken < or = 0.80 of
      their medication. We measured quality of life using the Minnesota Living with
      Heart Failure Questionnaire and the Short Form 36 and conducted a time to first
      event analysis of a composite end point including mortality, readmissions, and
      emergency department visits. RESULTS: The Intervention group showed higher
      knowledge scores at discharge and 1 year (P = .05). The risk of noncompliance in
      Intervention patients varied from 0.78 (95% CI 0.33-1.89) for ACE-I (13%
      Intervention, 17% Control) to 1.02 (0.49-2.12) for diuretics (23% Intervention,
      23% Control). Quality of life improved in both groups over time; the only
      difference between groups favored the Intervention (Minnesota Living with Heart
      Failure Questionnaire, P = .04). The composite end point occurred in 67% of
      control and 60% of Intervention patients (hazard ratio 0.85, 95% CI 0.55-1.30).
      CONCLUSIONS: An inhospital educational intervention improved knowledge and,
      possibly, quality of life and may be useful as part of a comprehensive compliance
      enhancing strategy in patients with HF.

PMID- 16290976
TI  - How do different indicators of cardiac pump function impact upon the long-term
      prognosis of patients with chronic heart failure?
AB  - BACKGROUND: The prognosis of patients with mild-moderate chronic heart failure
      (CHF) over a long-term follow-up period is more difficult to predict than for
      patients with more severe CHF in the short term. This study assessed the
      prognostic value of various indicators of cardiac pump function to gain insight
      into how different aspects of organ function impact upon prognosis. METHODS:
      Unselected, consecutive patients with CHF (n = 219, 166 men, mean [+/-SD] age 56
      +/- 13 years) who underwent symptom limited cardiopulmonary treadmill exercise
      testing with noninvasive estimation of cardiac output using carbon dioxide
      rebreathing techniques were followed up for a median period of 8.6 +/- 1.0 years
      in survivors. Cardiac power output (CPO) was calculated from the product of
      cardiac output and mean arterial pressure and cardiac reserve was estimated by
      subtracting resting from peak exercise CPO or cardiac output (CO). RESULTS: All
      cause mortality was 36% (78 deaths). Survivors had a significantly greater
      cardiac pumping reserve with the greatest difference seen in CPO reserve (+57%)
      and CO reserve (+49%) (both P < .001). Although various direct and indirect
      indicators of cardiac function were predictive of outcome on univariate analyses,
      multivariate analysis using the Cox proportional hazards model identified CO
      reserve to be the independent variable predictive of all-cause mortality, with a
      hazard ratio (95% CI) of 0.682 (0.612-0.757, P < .001) for each L/min increase in
      cardiac output reserve. Survival at 10 years in patients with tertiles of good,
      moderate, or poor cardiac output reserve was 89%, 63%, and 36.1%, respectively (P
      < .001). CONCLUSION: In this long-term follow-up study involving a cohort of
      unselected ambulatory patients with mild-moderate CHF, cardiac pumping reserve
      measured noninvasively by cardiopulmonary exercise testing was found to be the
      strongest independent predictor of prognosis.

PMID- 16290977
TI  - A simplified education program improves knowledge, self-care behavior, and
      disease severity in heart failure patients in rural settings.
AB  - BACKGROUND: Self-monitoring by heart failure (HF) patients of worsening symptoms
      caused by fluid overload is a cornerstone of HF care. Disease management has
      improved outcomes in HF; however, these resource-intensive programs are limited
      to urban centers and are generally unavailable in rural or limited health care
      access areas. This pilot study sought to determine whether a simplified education
      program focused on a single component of disease management (symptom recognition
      and management of fluid weight) could improve knowledge, patient-reported self
      care behavior, and HF severity in a rural setting. METHODS: This randomized
      clinical trial enrolled 36 rural HF patients into an intervention or control
      group. The intervention group received a simplified education program with a
      follow-up phone call focusing on symptom management delivered by a non-cardiac
      trained nurse. Patient knowledge, self-care behaviors, and HF severity (B
      natriuretic peptide [BNP]) were measured at enrollment and at 3 months. RESULTS:
      The sample was primarily white men and married with a mean age of 71 years and
      ejection fraction of 47%. There were no differences between groups in knowledge,
      self-care behaviors and BNP at baseline; however, knowledge and self-care
      behavior related to daily weights improved significantly at 3 months in the
      intervention group (P = .01 and .03, respectively). Although the changes in mean
      BNP at 3 months were in the hypothesized direction, the difference between the 2
      groups was not significant. CONCLUSIONS: A simplified education program designed
      for use in resource scarce settings improves knowledge and patient-reported self
      care behaviors. These findings are important in providing care to patients with
      HF in limited access settings but should be studied for longer periods in more
      heterogeneous populations.

PMID- 16290979
TI  - Vulnerabilities of patients recovering from an exacerbation of chronic heart
      failure.
AB  - BACKGROUND: Many rehospitalizations for heart failure (HF) are preventable as
      they are precipitated by modifiable factors. High early readmission rates suggest
      that patients commonly are discharged from HF hospitalizations with such problems
      unaddressed. The purpose of this study was to describe the prevalence of multiple
      risk factors for rehospitalization in patients recently discharged from a
      hospitalization for decompensated HF. METHODS AND RESULTS: The following
      potentially modifiable risk factors for rehospitalization were evaluated in 202
      patients: functional status; whether the patient lived alone; presence of
      anxiety, depression, or poor quality of life; and symptom status and adherence to
      prescribed medications, low-sodium diet, and symptom monitoring recommendations.
      Most patients were severely functionally impaired (70% New York Heart Association
      [NYHA] functional class III/IV). Of the 28% of patients who lived alone, 50% were
      rated as NYHA functional class III or IV. Fifty percent of patients were anxious,
      whereas 69% of patients were depressed. Health-related quality of life was
      substantially impaired. Patients reported substantial symptom burden. Adherence
      with recommended self-care strategies was poor: 14% weighed themselves daily, 9%
      of patients reported monitoring for symptoms of worsening HF, 31% could not name
      any symptom, and only 34% of patients taking all medications as prescribed. A
      total of 23% of patients had all of the following risk factors: NYHA functional
      class III or IV, lived alone, > or =1 comorbidities, and were depressed or
      anxious. CONCLUSIONS: Patients newly discharged from a hospitalization for HF
      exhibit many psychosocial and behavioral risk factors for rehospitalization,
      although they have been judged clinically stable.

PMID- 16290978
TI  - Blood volume and brain natriuretic peptide in congestive heart failure: a pilot
      study.
AB  - BACKGROUND: Brain natriuretic peptide (BNP) levels rise in response to stretch of
      ventricular myocytes or increases in wall tension, as in congestive heart failure
      (CHF). Brain natriuretic peptide can be released in bursts, but nonetheless, BNP
      levels may lag behind clinical changes. We postulated that concomitant
      measurement of blood volume (BV), BNP, and hemodynamics during treatment of CHF
      may elucidate interrelationships among changes in these parameters. METHODS: We
      studied 10 male patients, aged 60 +/- 8 years, who were admitted for pulmonary
      catheter-guided treatment of CHF. Hemodynamics, venous BNP, and blood and plasma
      volumes were measured at baseline before treatment and again on the following
      morning after 12 to 24 hours of acute treatment for CHF. RESULTS: At baseline,
      all 10 patients exhibited marked expansion of BV at 29% +/- 19%. At baseline,
      increased systolic pulmonary artery pressure correlated with BV (r = 0.615) and
      diastolic pulmonary artery pressure (PAD) with BV (r = 0.609). After treatment,
      there was an inverse correlation between change (decline) in expanded BV and
      change (improvement) in mixed venous oxygenation (r = -0.775) and a positive
      correlation with central venous pressure (CVP) (r = 0.710). Poor correlation was
      found between BNP and any hemodynamic parameter. Little correlation was found
      between absolute BNP and BV before or after treatment (r = -0.127 and -0.126,
      respectively). CONCLUSION: In this pilot study, changes in BV with treatment
      correlate better with hemodynamics than do changes in BNP, likely reflecting the
      lag in BNP response to treatment and its tendency to reflect long-term rather
      than instantaneous volume status. These preliminary data suggest that BV may be a
      more accurate guide in optimizing CHF treatment than BNP.

PMID- 16290980
TI  - Economic impact of the reduced incidence of atrial fibrillation in patients with
      heart failure treated with enalapril.
AB  - BACKGROUND: Atrial fibrillation (AF) in the setting of heart failure (HF) is
      linked to embolic stroke and exacerbation of HF. The rate of new-onset AF in
      patients with left ventricular dysfunction and mild to moderate HF enrolled in
      the SoLVD trials was significantly lower with enalapril than with placebo (5.4%
      vs 24% over 2.9 years, P < .0001). The objective of this study was to predict
      economic benefits over 5 and 10 years of reduced AF incidence in patients
      receiving enalapril for the treatment of HF from a Canadian third-party payer
      perspective. METHODS: Consequences of reduced incidence of AF in enalapril
      treated patients were modeled using a Markov model. Patients were assigned to 1
      health state: no AF, AF, poststroke, or death, and moved from one state to the
      other according to published incidence rates. It was assumed that most patients
      with AF would receive warfarin for stroke prevention. Resource use and costs were
      mostly retrieved from published Canadian studies. RESULTS: Reduced incidence of
      AF resulted in savings of 382 dollars and 525 dollars per patient treated with
      enalapril over 5 and 10 years, respectively, which stemmed mainly from reduced AF
      hospitalization and less need for warfarin and amiodarone. Sensitivity analyses
      demonstrated that enalapril becomes more cost saving as the baseline risk for
      embolic stroke in patients with AF increases and the use of warfarin prophylaxis
      decreases. CONCLUSIONS: Reduced incidence of AF with enalapril leads to
      significant clinical and economic advantages on top of the already well
      established benefits of enalapril for patients with HF.

PMID- 16290981
TI  - Comparative efficacy of nebivolol versus carvedilol on left ventricular function
      and exercise capacity in patients with nonischemic dilated cardiomyopathy. A 12
      month study.
AB  - PURPOSE: To compare the efficacy of nebivolol versus carvedilol on left
      ventricular (LV) function and exercise capacity in patients with nonischemic
      dilated cardiomyopathy (NIDC). METHODS: After enrollment in this double-blind
      trial, 72 patients, aged 55 +/- 9.5 years, with NIDC, LV ejection fraction (LVEF)
      < 45%, New York Heart Association classes II to III, were randomized to either
      nebivolol (34 patients) or carvedilol (38 patients) and were evaluated through
      echocardiography and exercise tests at baseline and 3 and 12 months after
      treatment. RESULTS: During follow-up, 4 patients discontinued nebivolol, although
      3 patients stopped carvedilol. Patients in both the nebivolol and carvedilol
      groups showed a steady improvement in New York Heart Association class (P = .002
      and < .001, at 12 months, respectively) and LVEF (P = .001 and < .001, at 12
      months, respectively) that became significant from 3-month follow-up on.
      Intergroup analysis showed that carvedilol group had a greater increase in LVEF
      at 3 (P = .04) and 12 (P = .02) months' follow-up compared with nebivolol group.
      Advanced diastolic dysfunction regressed to earlier stages in carvedilol patients
      after 3 (P = .02) and 12 (P = .01) months' treatment, whereas in the nebivolol
      group, a significant improvement in diastolic dysfunction was found at the 12
      months' follow-up (P = .02). Exercise duration improved in both groups at 12
      months' follow-up (both P = .01), but in the nebivolol group, there was an
      initial deterioration at 3 months (P = .07). CONCLUSIONS: Both nebivolol and
      carvedilol appear relatively safe, with beneficial effects on LV systolic and
      diastolic function as well as exercise capacity in patients with NIDC after 12
      months' treatment. However, carvedilol exhibits more favorable effects on LV
      function than does nebivolol.

PMID- 16290982
TI  - Intracoronary administration of autologous bone marrow mononuclear cells after
      induction of short ischemia is safe and may improve hibernation and ischemia in
      patients with ischemic cardiomyopathy.
AB  - BACKGROUND: Recent studies suggest that myocardial administration of stem cells
      improves perfusion and function of ischemic myocardium. The present study
      evaluated the safety and efficacy of simple intracoronary administration of
      mononuclear autologous bone marrow (BM) cells in patients with ischemic
      cardiomyopathy without revascularization option. METHODS AND RESULTS: We enrolled
      6 consecutive patients with ischemic cardiomyopathy, who were in New York Heart
      Association classes III to IV despite optimal medical treatment without
      revascularization options and who, on dobutamine stress echocardiograph (DSE),
      were found to have left ventricular ejection fraction < 35% with significant
      hibernation and ischemia in at least 2 myocardial segments. BM cell suspension
      was collected, and on the next day, during coronary angiography, mild ischemia
      was induced by a short balloon inflation in each coronary conduit with a TIMI
      flow of > or = 2 followed by slow infusion of up to 50 mL of BM cells suspension
      to each conduit. At baseline and 4 months' follow-up, patients underwent clinical
      evaluation, Holter monitoring, and DSE. BM infusion was successful in all
      patients. One patient developed postprocedure hypotension and troponin increase.
      At 4 months' follow-up New York Heart Association class improved from 3.5 +/- 0.5
      to 2.3 +/- 1.0, P = .04, and resting ejection fraction improved from 25% +/- 7%
      to 28% +/- 8%, P = .055. We observed improvement in resting wall motion score
      only in the segments with hibernation in baseline DSE (2.3 +/- 0.5 to 2.0 +/-
      0.6, P = .03) and improvement in high-dose dobutamine wall motion score, only in
      segments showing significant ischemia at baseline DSE (2.5 +/- 0.5 to 2.0 +/-
      0.6, P = .001). There were no clinical arrhythmias or increased arrhythmia burden
      by Holter monitoring. CONCLUSIONS: In patients with severe symptomatic ischemic
      cardiomyopathy, mild induction of ischemia followed by intracoronary infusion of
      unmanipulated autologous BM is feasible and safe and may improve hibernation and
      ischemia.

PMID- 16290984
TI  - "Full metal jacket" (stented length > or =64 mm) using drug-eluting stents for de
      novo coronary artery lesions.
AB  - BACKGROUND: Stented segment length was a predictive factor for restenosis in the
      bare metal stent era. The objective of the study was to evaluate the medium-term
      clinical outcome and the potential for adverse effects when very long segments
      (ie, > or =64 mm of stented length) are treated by drug-eluting stent (DES)
      implantation, an approach colloquially referred to as a "full metal jacket."
      METHODS: Since April 2002, we have used DES as the default stent for all
      percutaneous coronary interventions. From our prospective institutional database
      we identified 122 consecutive patients, with de novo coronary lesions, in whom a
      coronary artery was treated with at least 64 mm of overlapping DES: 81 patients
      were treated with sirolimus-eluting stents and 41 with paclitaxel-eluting stents.
      RESULTS: The mean number of stents per lesion was 3.3 +/- 1.1, and the median
      stented length was 79 mm (range 64-168 mm). Periprocedural Q-wave myocardial
      infarction (MI) occurred in 2 patients (1.6%) and subacute stent thrombosis in 1
      patient (0.8%). During 1-year follow-up, 5 patients (4.1%), including 3 patients
      treated for acute MI with cardiogenic shock, died and 10 patients (8.2%) had
      nonfatal MI (creatine kinase-MB >3 times). The 1-year target vessel
      revascularization rate was 7.5% and the overall incidence of major adverse
      cardiac events was 18%. Outcomes in sirolimus-eluting stents and paclitaxel
      eluting stents groups did not differ statistically. CONCLUSIONS: The use of DES
      for the treatment of diffuse lesions was associated with a low rate of repeat
      revascularization, irrespective of stent type. No safety concerns were raised at
      medium-term follow-up.

PMID- 16290983
TI  - A randomized trial in patients undergoing percutaneous coronary angioplasty:
      roxithromycin does not reduce clinical restenosis but angioplasty increases
      antibody concentrations against Chlamydia pneumoniae.
AB  - BACKGROUND: Elevated antibodies against Chlamydia pneumoniae have been associated
      with coronary artery disease. In patients undergoing percutaneous coronary
      angioplasty, we therefore investigated the effect of roxithromycin on symptomatic
      restenosis and determined antichlamydial antibodies as well as inflammatory and
      immunological parameters. METHODS: A total of 327 patients undergoing coronary
      angioplasty were randomized to roxithromycin or placebo and followed-up for 1
      year. Antibodies were determined by microimmunofluorescence and enzyme-linked
      immunosorbent assay; C-reactive protein, interleukin-10, tumor necrosis factor
      alpha (TNF-alpha), and eotaxin were determined by enzyme-linked immunosorbent
      assay. RESULTS: Although the frequency of restenosis was not affected by
      roxithromycin (25 restenoses vs 32 in the control group), antichlamydial
      antibodies increased during follow-up (anti-CP IgG +12 +/- 2%, P < .001).
      Concentrations of TNF-alpha and eotaxin increased as well (TNF-alpha +9 +/- 1%
      and eotaxin +10 +/- 2%) and correlated with antichlamydial antibody
      concentrations (TNF-alpha, r = 0.23, P = .02; eotaxin, r = 0.32, P = .002).
      CONCLUSIONS: Treatment with roxithromycin was not associated with a reduction of
      symptomatic restenoses. During follow-up, a marked increase in antichlamydial
      antibodies, TNF-alpha, and eotaxin was observed, suggesting that angioplasty
      induced plaque rupture induces a specific immunological response without
      activation of inflammatory mechanisms as represented by C-reactive protein.
      Whether this mechanism occurs in all plaque ruptures remains to be determined.

PMID- 16290985
TI  - Admission glucose concentrations independently predict early and late mortality
      in patients with acute myocardial infarction treated by primary or rescue
      percutaneous coronary intervention.
AB  - BACKGROUND: In patients with acute myocardial infarction (MI), increased plasma
      glucose levels at hospital admission are associated with worse outcome. We aimed
      to assess the predictive value of admission glucose concentrations on short- and
      long-term mortality in patients with acute MI undergoing primary or rescue
      percutaneous coronary intervention (PCI). METHODS: We analyzed the 30-day and
      long-term (mean follow-up 3.7 years) outcome of 978 patients prospectively
      included in a single-center registry of patients with acute MI treated with PCI
      within 24 hours after onset of symptoms. Patients were classified according to
      plasma glucose levels at admission: < 7.8 mmol/L (group I, n = 322), 7.8 to 11
      mmol/L (group II, n = 348), and > 11.0 mmol/L (group III, n = 308). RESULTS:
      Mortality at 30 days was 1.2% in group I, 6.3% in group II, and 16.6% in group
      III (P < .001). After multivariate adjustment for age, the presence of
      cardiogenic shock, and TIMI 3 flow after PCI, the association of mortality with
      glucose classification remained significant (P value for trend = .003). The
      relative risk of death at 30 days for group III versus group I was 3.9 (95% CI
      1.2-13.2). During long-term follow-up, mortality was similar in groups I and II.
      However, in group III adjusted mortality remained significantly increased
      compared with group I (relative risk 1.76, CI 1.01-3.08). CONCLUSIONS: In
      patients undergoing emergency PCI for acute MI, glucose levels at hospital
      admission are predictive for short- and long-term survival. Knowledge of
      admission glucose levels may improve initial bedside risk stratification.

PMID- 16290986
TI  - Relationship of a comprehensive panel of plasma oxidized low-density lipoprotein
      markers to angiographic restenosis in patients undergoing percutaneous coronary
      intervention for stable angina.
AB  - BACKGROUND: This study was performed to assess the relationship between oxidized
      low-density lipoprotein (OxLDL) and restenosis. OxLDL induces up-regulation of
      inflammatory genes and cytokines and recruits monocytes to the vessel wall.
      Elevated levels of monocytes post-percutaneous coronary intervention (PCI) are
      associated with in-stent restenosis. METHODS AND RESULTS: One hundred forty-one
      patients with stable angina pectoris had serial blood samples drawn before PCI
      (68% balloon only, 32% stent), immediately post-PCI and at 6 and 24 hours, 3
      days, 1 week, and 1, 3, and 6 months. Plasma levels of OxLDL-E06, a measure of
      oxidized phospholipid (OxPL) content on apoB-100 detected by antibody E06
      (OxPL/apoB), autoantibodies to malondialdehyde-LDL and copper-oxidized LDL, and
      apoB-immune complexes were measured in all samples. Quantitative and qualitative
      coronary angiography was performed with 94% angiographic follow-up. Restenosis
      was defined as >50% diameter stenosis (%DS). The overall angiographic restenosis
      rate was 32% (39% in balloon group, 16% in stent group). OxPL/apoB levels rose
      significantly and OxLDL autoantibody titers decreased immediately post-PCI in
      patients both with and without restenosis, but there were no significant
      differences among groups. There was also no relationship of any OxLDL marker to
      lesion length, %DS, or minimal lumen diameter. No differences were noted in stent
      versus balloon-treated patients. CONCLUSIONS: Serial measurement of a
      comprehensive panel of circulating OxLDL markers after uncomplicated PCI for
      stable angina does not predict restenosis.

PMID- 16290987
TI  - Left ventricular remodeling after primary coronary angioplasty in patients
      treated with abciximab or intracoronary adenosine.
AB  - BACKGROUND: Primary angioplasty is the best treatment of acute myocardial
      infarction but fails to achieve adequate myocardial reperfusion in 25% to 30% of
      patients, despite TIMI grade 3 flow. Drug treatment aimed at reducing the no
      reflow phenomenon may improve myocardial salvage, thus preventing left
      ventricular remodeling. Our aim was to evaluate the impact of abciximab and
      adenosine on immediate angiographic results and on 6-month left ventricular
      remodeling. METHODS: Ninety consecutive patients undergoing primary angioplasty
      with coronary stenting were randomized in a sequential alternating fashion to
      standard abciximab treatment (ABCX) group, intracoronary adenosine distal to the
      occlusion (ADO) group, or neither (CTRL) group. All patients underwent a clinical
      and echocardiographic follow-up at 1 and 6 months. The primary end point was the
      prevalence of 6-month left ventricular remodeling. RESULTS: Baseline clinical,
      echocardiographic, and angiographic characteristics were similar. Mean final
      corrected TIMI frame count was 17 +/- 9, 16 +/- 12, and 23 +/- 11 frames in ABCX,
      ADO, and CTRL patients, respectively (P = .002). Angiographic no-reflow was
      observed in 7%, 13%, and 17% of ABCX, ADO, and CTRL patients, respectively (P >
      .20). At 6 months, left ventricular remodeling occurred in 7%, 30%, and 30% of
      ABCX, ADO, and CTRL patients, respectively (P = .045), with a percent increase in
      end-diastolic volume of 5% +/- 13%, 15% +/- 15%, and 12% +/- 18% (P = .04).
      CONCLUSIONS: During primary angioplasty, abciximab enhances myocardial
      reperfusion, translating into a reduced incidence of 6-month left ventricular
      remodeling. In contrast, adenosine administration improves angiographic results
      but does not prevent left ventricular remodeling.

PMID- 16290988
TI  - Early versus periprocedural administration of abciximab for primary angioplasty:
      a pooled analysis of 6 studies.
AB  - BACKGROUND: The 2004 ACC/AHA guidelines on ST-elevation myocardial infarction
      state that it is reasonable to start treatment with abciximab as early as
      possible before primary percutaneous coronary intervention (PCI). We investigated
      the potential benefit of early use of abciximab by pooling data from all the
      available studies. METHODS: Six prospective studies were identified that had
      allocated 260 patients to receive early abciximab (either prehospital or soon
      after the patient arrived in hospital) and 342 to receive late abciximab (at the
      time of PCI). RESULTS: TIMI flow grade 2 or 3 was present in 42% of the early
      group compared with 29% in the late group (P = .001). After PCI, 59% of patients
      in the early group showed ST-resolution >or = 70%, compared with 41% in the late
      group (P = .003). The composite clinical outcomes death, new myocardial
      infarction, or repeat target vessel revascularization at 30 days occurred in 7.3%
      of the early group compared with 9.7% in the late group (odds ratio 0.73, 95% CI
      0.41-1.32) and death alone occurred in 2.7% versus 4.7%, respectively (odds ratio
      0.56, 95% CI 0.23-1.39). CONCLUSIONS: Early administration of abciximab improves
      epicardial patency (TIMI flow) before PCI and results in better myocardial tissue
      perfusion (ST-resolution) after the procedure. The promising effects on clinical
      outcomes need to be tested in larger studies.

PMID- 16290989
TI  - Coronary artery calcifications in the long-term follow-up of Kawasaki disease.
AB  - BACKGROUND: To determine if detection of coronary artery calcifications in
      patients with Kawasaki disease may serve as a noninvasive predictor of future
      coronary artery events. METHODS: A prospective, cohort pilot study that included
      18 patients with Kawasaki disease > 1 year from the acute disease was performed
      including 9 patients with coronary abnormalities during the acute illness (Group
      1) and 9 without coronary abnormalities (Group 2). Patients were classified by
      echocardiography as having none, resolved, or residual coronary artery
      abnormalities. Electron beam computed tomography (EBCT) scans were completed
      using the Agatson coronary calcium scoring system. Intermediate follow-up was
      performed 2.5 years after EBCT to determine if clinically significant coronary
      artery events (myocardial infarction or sudden death) had occurred. RESULTS: Late
      echocardiographic abnormalities corresponded with the early echocardiographic
      abnormalities in 5 of 9 patients (P = .029) in Group 1. The late
      echocardiographic abnormalities significantly correlated with detection of
      calcifications by EBCT in 4 of 5 patients (95% CI 28%-99%). One patient with
      residual coronary abnormalities and coronary artery calcifications with the
      highest calcium score subsequently had a sudden death. Detection of coronary
      artery calcifications may be predictive of sudden death (P = .056). No residual
      echocardiographic abnormalities, coronary artery calcifications, or coronary
      artery events occurred in Group 2 patients. CONCLUSIONS: Patients with Kawasaki
      disease with residual coronary abnormalities show EBCT evidence of coronary
      artery calcifications. Detection of coronary artery calcifications may be useful
      for risk stratification in the long-term management of patients with Kawasaki
      disease.

PMID- 16290990
TI  - Sex differences in depression after coronary artery bypass graft surgery.
AB  - BACKGROUND: Previous research suggests that after coronary artery bypass graft
      (CABG) surgery, women fare worse than men. This study investigates sex
      differences in depression during recovery from CABG surgery. METHODS: We followed
      137 patients (72 men, 65 women) undergoing elective isolated first CABG surgery
      between July 2003 and April 2004. Patients were interviewed < or = 28 days before
      surgery and between 6 and 12 weeks after surgery. Patients completed a structured
      diagnostic interview for major depressive disorder (MDD) and the Beck Depression
      Inventory (BDI). Clinical data were retrieved from patient charts. RESULTS:
      Prevalence of MDD before surgery was 28.2%, but decreased to 16.4% after surgery
      (P = .038). Women had significantly more depressive symptoms than men pre-CABG,
      with a mean BDI of 12.5 (95% CI 10.6-14.4) for women versus 8.0 (95% CI 6.3-9.8)
      for men (P = .0001), but not post-CABG. There was a significant sex-by-time
      interaction with depressive symptoms in women improving almost 6-fold more than
      in men, with BDI change scores of 4.1 (95% CI 2.0-6.1) for women versus 0.7 (95%
      CI-1.0-2.5) for men (P = .008). The interaction remained significant after
      adjusting the model for the predetermined baseline characteristics education,
      social support, and operative risk. CONCLUSIONS: Women had more depressive
      symptoms than men pre-CABG, but improved to a level comparable to men post-CABG.
      Women benefited from CABG as much or more than men in terms of their mental
      health. Preoperative depressive symptoms should not preclude women from CABG
      surgery.

PMID- 16290991
TI  - The association between prior percutaneous coronary intervention and short-term
      outcomes after coronary artery bypass grafting.
AB  - BACKGROUND: Increasingly, patients are being referred for coronary artery bypass
      grafting (CABG) for management of symptoms after prior percutaneous coronary
      intervention (PCI). In this study, we assessed the impact of prior PCI on
      inhospital mortality after CABG. METHODS: Perioperative data were collected on
      patients who underwent first-time CABG at 2 surgical centers. Patients who
      underwent PCI and CABG during the same admission were excluded. Patients with
      prior PCI were compared with patients with no prior PCI, and the risk-adjusted
      impact of prior PCI on inhospital mortality after CABG was determined using both
      multivariate techniques and propensity score matching techniques. RESULTS: Six
      thousand thirty-two patients met inclusion criteria. Patients with prior PCI were
      less likely to be between the ages of 70 and 80 (P < .0001), to have an ejection
      fraction <0.40 (P < .0001), and to have 3-vessel/left main disease (P < .0001).
      They were, however, more likely to have Canadian Cardiovascular Society class IV
      symptoms (P < .0001) and to have an urgent status (P = .02). Rates of inhospital
      mortality after CABG were higher in patients with prior PCI (3.6% vs 2.3%, P =
      .02). Using multivariate techniques, prior PCI emerged as an independent
      predictor of postoperative inhospital mortality (odds ratio 1.93, P = .003). When
      patients with prior PCI were matched to patients with no prior PCI using
      propensity scores, inhospital mortality remained higher among patients with prior
      PCI (3.6% vs 1.7%, P = .01). CONCLUSION: Patients with prior PCI presented for
      CABG with less comorbidity and diminished coronary disease; yet, they had more
      advanced symptoms and greater urgency. After adjusting for these differences,
      prior PCI emerged as an independent predictor of inhospital mortality after CABG.

PMID- 16290992
TI  - The relationship between C-reactive protein and subclinical cardiovascular
      disease in the Diabetes Heart Study (DHS).
AB  - BACKGROUND: Epidemiological studies suggest that levels of C-reactive protein
      (CRP) predict cardiovascular disease (CVD). We have evaluated the relationship
      between CRP and subclinical CVD in a study cohort at high risk of CVD. METHODS:
      The DHS is a single-center, family-based study of the genetic and environmental
      components of CVD in type 2 diabetes mellitus (T2DM). We evaluated 666 subjects
      (551 T2DM affected and 115 unaffected) with an average age of 61 years. Measures
      of coronary artery calcium (CAC), intimal-medial thickness (IMT) of the common
      carotid artery, and CRP were obtained on all subjects. RESULTS: C-reactive
      protein is positively and significantly associated with female sex, body mass
      index, and smoking and is negatively and significantly associated with age and
      statin use. Generalized estimating equations were used to test whether CRP was
      associated with each subclinical CVD measure (presence/absence of CAC, quantity
      of CAC, and IMT) adjusting for covariates and correlation among siblings.
      Stratified analyses were conducted to examine whether these associations differed
      across sex and statin use. In the overall analysis, CRP was not significantly
      associated with IMT or presence of CAC but was negatively and significantly
      associated with quantity of CAC (P = .01). When covariates were added, the
      relationship was no longer significant. Similar patterns were observed in
      stratified analyses based on sex, statin use, and diabetes status: weak but
      negative association of CAC with CRP, which became nonsignificant with adjustment
      for covariates. CONCLUSIONS: In a population at high risk for CVD, there was no
      evidence of incremental association of CRP levels with measures of subclinical
      CVD.

PMID- 16290993
TI  - Alterations of high-density lipoprotein subclasses in endogenous
      hypertriglyceridemia.
AB  - BACKGROUND: To investigate the alterations of high-density lipoprotein (HDL)
      subclasses in endogenous hypertriglyceridemic subjects. METHODS: Apolipoprotein A
      I contents of plasma HDL subclasses were quantitated by 2-dimensional gel
      electrophoresis in 236 normolipidemic subjects (including 146 males and 90
      females) and 176 endogenous hypertriglyceridemic subjects (including 103 males
      and 73 females). RESULTS: Apolipoprotein A-I contents of small-sized pre-beta1
      HDL and HDL3a were significantly higher (P < .01 and P < .01, respectively), but
      those of large-sized HDL2a and HDL2b were significantly lower (P < .01 and P <
      .01, respectively) in hypertriglyceridemic subjects versus normolipidemic
      subjects. Moreover, with the elevation of triglyceride levels, small-sized pre
      beta1-HDL and HDL3a increased successively; however, large-sized HDL2a and HDL2b
      decreased successively. Males had significantly higher apolipoprotein A-I
      contents of small-sized pre-beta1-HDL and HDL3b (P < .05 and P < .05,
      respectively), but lower contents of large-sized HDL2b (P < .01) than females in
      both normolipidemic and hypertriglyceridemic subjects. CONCLUSIONS: The particle
      size of HDL shifted toward smaller size in hypertriglyceridemic subjects,
      especially in male subjects. Of note, the shift was more obvious with the
      elevation of triglyceride levels. The changes mentioned above indicate that HDL
      maturation might be abnormal and reverse cholesterol transport might be weakened.

PMID- 16290994
TI  - Clinical profile and outcomes of diabetic and nondiabetic patients in cardiac
      rehabilitation.
AB  - BACKGROUND: Patients with diabetes mellitus have increased risk of cardiovascular
      disease; however, there are limited data addressing cardiac rehabilitation in
      these patients. This study assessed the effectiveness of participation in cardiac
      rehabilitation on clinical outcomes after myocardial infarction and/or
      revascularization procedures in diabetic and nondiabetic patients. METHODS:
      Analysis on 1505 patients completing a minimum of 7 weeks of a 12-week cardiac
      rehabilitation program included fasting lipid profile and glucose, body mass
      index, and metabolic equivalent time in patients with diabetes (n = 292) and
      without diabetes (n = 1213). RESULTS: There were significant improvements in
      total cholesterol, low-density lipoprotein cholesterol (LDL-C) and high-density
      lipoprotein cholesterol (HDL-C) in each group after cardiac rehabilitation.
      Diabetic women and nondiabetic men had the greatest improvement in HDL-C, with an
      improvement of 4.9% in diabetic women (P = .02) and an improvement of 4.1% in
      nondiabetic men (P < or = .0001). On completion of cardiac rehabilitation, both
      diabetic and nondiabetic patients were at National Cholesterol Education Program
      Adult Treatment Panel III goals in total cholesterol, LDL-C, HDL-C, and
      triglycerides at a higher rate. However, patients with diabetes did not reach
      National Cholesterol Education Program goals for HDL-C, total cholesterol, and
      triglycerides as effectively as nondiabetic patients. Exercise capacity improved
      by 28.1% in diabetic patients after cardiac rehabilitation (P < .0001).
      Improvement in outcomes in the patients with diabetes occurred without
      significant change in body mass index. CONCLUSIONS: These results suggest that
      participation in a comprehensive cardiac rehabilitation program integrates care
      of patients with chronic conditions such as diabetes to achieve comparable
      cardiac risk factor reduction as achieved with nondiabetic patients.

PMID- 16290995
TI  - Women in cardiac rehabilitation: outcomes and identifying risk for dropout.
AB  - BACKGROUND: Women are underrepresented in cardiac rehabilitation (CR). Few
      reports describe outcomes and explore factors that may be barriers to CR
      participation among women. The purposes of this study were to (1) compare
      baseline characteristics between women who completed and did not complete CR, (2)
      identify factors associated with women completing CR, and (3) describe outcomes
      among completers. METHODS: Study sample included women (n = 228) with coronary
      heart disease enrolled in CR at an academic medical center's program (January
      1996-August 2003). Baseline differences between completers and noncompleters were
      compared; multivariate regression analyses identified factors associated with
      completers. Outcome measures included lipid levels, 6-minute walk distances, body
      mass index, Beck Depression Inventory II (BDI-II), self-reports of diet, physical
      activity, smoking, and perceived health status. RESULTS: Mean age was 62 +/- 11
      years, 44% were nonwhite, and 42% were stratified as high risk. Dyslipidemia was
      the most common risk factor (85%) followed by hypertension (81%), low physical
      activity (74%), obesity (53%), diabetes (39%), and smoking (18%). BDI-II scores
      were elevated (> or = 14) in 31% of women. In the adjusted multivariate
      regression model, completers were less likely to be obese (adjusted odds ratio
      [AOR] 0.28, CI 0.10-0.76, P = .01) or have elevated BDI-II scores (AOR 0.87, CI
      0.81-0.95 P = .001) than noncompleters. Completers achieved significant
      improvements in all outcome measures (all P < .05) except for high-density
      lipoprotein. CONCLUSION: Women enrolled in CR had a high risk factor burden and
      those completing achieved significant benefits. Women not completing CR were more
      likely to be obese or have depressive symptoms which may serve as barriers to
      completing CR.

PMID- 16290996
TI  - Burst bicycle exercise facilitates diagnosis of latent long QT syndrome.
AB  - OBJECTIVES: The aim of this study was to develop a diagnostic technique to detect
      latent long QT syndrome. BACKGROUND: Asymptomatic patients with genetically
      diagnosed long QT syndrome (LQTS) may have a normal resting QT interval, yet
      remain at risk for cardiac events. We hypothesized that the QT response during a
      novel burst exercise protocol simulating clinical events might distinguish
      patients with "latent LQTS" from healthy subjects. METHODS: A burst bicycle
      protocol was performed on 31 healthy subjects and 31 patients with LQTS (13 LQT2,
      3 LQT1, 15 unknown genotype). The bicycle exercise protocol involved sudden
      maximal exertion against a fixed workload (200 W) for 1 minute. Digitized 12-lead
      eletrocardiograms were acquired every 10 seconds at baseline for 1 minute, during
      1 minute of burst exercise, and for 5 minutes during recovery. Patients with LQTS
      were segregated according to whether the baseline QTc was normal (< or = 440
      milliseconds, n = 13) or abnormal (> 440 milliseconds, n = 18). RESULTS: During
      exercise, the QTc increased to a greater extent in the group with latent LQTS
      (DeltaQTc 98 +/- 36 milliseconds) in comparison with controls (DeltaQTc 65 +/- 19
      milliseconds, P < .01) and those with baseline QTc prolongation (DeltaQTc 17 +/-
      70 milliseconds, P < .01). In patients with a normal baseline QTc, a DeltaQTc >
      85 milliseconds had a sensitivity of 85% and a specificity of 86% for LQTS (P =
      .0004). CONCLUSION: Marked QTc prolongation during burst bicycle ergometry
      provides potentially diagnostic information for patients with normal baseline QTc
      and suspected LQTS.

PMID- 16290997
TI  - Indications for internal cardioverter defibrillator implantation predict time to
      first shock and the modulating effect of beta-blockers.
AB  - BACKGROUND: Patients receive implantable cardioverter defibrillator (ICD) for
      varying indications. Whether these indications influence the time to first ICD
      shock is suspected but not confirmed. The modulating effect of beta-blockers on
      shock-free survival is not fully elucidated. METHOD: A retrospective analysis of
      230 consecutive patients (age 63 +/- 14 years, 79% men, 75% ischemic, 70% beta
      blockers) implanted with an ICD was performed. Patients were divided into 4
      groups depending on the ICD indication: groups A (secondary prevention of sudden
      death), B (left ventricular ejection fraction < or = 35% and positive
      electrophysiology study [EPS]), C (left ventricular ejection fraction < or = 35%
      and negative EPS or no EPS performed), and D (patients who did not meet inclusion
      criteria for groups A, B, or C). Time to shock was analyzed by the Kaplan-Meier
      method. RESULTS: During a mean follow-up of 489 +/- 280 days, 57 (24.7%) patients
      received 82 shocks (49% appropriate). The 1-year shock-free survival for patients
      in groups A, B, C, and D were 57%, 77%, 79%, and 91%, respectively (P = .03), for
      total shocks and 75%, 92%, 92%, and 100%, respectively (P = .007), for
      appropriate shocks. For patients in group A, the use of beta-blockers increased
      the 1-year shock-free survival from 48% to 61% for total shocks and from 65% to
      79% for appropriate shocks. CONCLUSION: Time to first shock is determined by the
      indication for ICD implantation and is not predicted by the results of EPS.
      Patients with secondary indications for ICD implantation are at highest risk of
      shocks and may deserve consideration for prophylactic antiarrhythmic drugs. beta
      Blockers increase the time to first ICD shock in patients implanted for secondary
      prevention of sudden death.

PMID- 16290998
TI  - Effect of C-reactive protein reduction on paroxysmal atrial fibrillation.
AB  - BACKGROUND: C-reactive protein (CRP) lowering is associated with a reduction in
      recurrent and permanent atrial fibrillation. This study sought to determine
      whether CRP lowering also results in a reduction of paroxysmal atrial
      fibrillation (PAF) during daily life. METHODS AND RESULTS: We enrolled 80
      patients with proven PAF, CRP between 0.8 and 13 mg/L, and at least 1 episode of
      PAF on ambulatory electrocardiographic monitoring. Forty patients were randomized
      to placebo (placebo group) and 40 to atorvastatin (treatment group). Plasma CRP
      levels and ambulatory monitoring were repeated after 4 to 6 months of therapy.
      The 2 groups were comparable with respect to baseline characteristics, number of
      episodes of PAF, and baseline plasma CRP levels. The treatment group had lower
      median CRP levels at study end and experienced a significant reduction in the
      number of episodes of PAF compared with the placebo group. Paroxysmal atrial
      fibrillation was completely resolved in 26 (65%) of 40 patients in the treatment
      group versus 4 (10%) of 40 in the placebo group. The treatment group exhibited a
      highly significant reduction in PAF (P < .001). By logistic regression, treatment
      with atorvastatin was an independent predictor of PAF resolution. CONCLUSIONS: C
      reactive protein lowering with atorvastatin appears to be effective in
      eliminating PAF during daily life in a significant proportion of patients.

PMID- 16290999
TI  - Is ambulatory monitoring for "community-acquired" syncope economically
      attractive? A cost-effectiveness analysis of a randomized trial of external loop
      recorders versus Holter monitoring.
AB  - BACKGROUND: Out patient ambulatory monitoring is often performed in patients with
      syncope that present in the primary care setting to include or exclude an
      arrhythmia. The cost-effectiveness of 2 monitoring strategies was assessed in a
      prospective randomized trial. METHODS: One hundred patients referred for
      ambulatory monitoring with syncope or presyncope were randomized to a 1-month
      external loop recorder (n = 49) or 48-hour Holter monitor (n = 51). Patients were
      offered crossover if there was failed activation or no symptom recurrence. The
      primary end point was symptom-rhythm correlation during monitoring. Direct costs
      were calculated based on the 2003 Ontario Health Insurance Plan fee schedule,
      combined with calculation of labor, materials, service, and overhead for
      diagnostic testing and related equipment. RESULTS: Before enrollment, the cost of
      all previous health care resource use was USD 472 +/- USD 397 (range USD 21-USD
      1965). In the loop recorder group, 63% of patients had symptom recurrence and
      successful activation, compared with 24% in the Holter group (P < .0001). The
      cost per Holter was USD 177.64, and per loop recorder, USD 533.56, with a similar
      cost per diagnosis with the 2 techniques. The incremental cost-effectiveness
      ratio of the loop recorder was USD 901.74 per extra successful diagnosis. A
      strategy of Holter followed by offered loop recorder trended toward lower cost
      than initial loop recorder followed by Holter (USD 481 +/- USD 267 vs USD 551 +/-
      USD 83, P = .08), but was associated with a lower overall diagnostic yield (49%
      vs 63%) and a resultant higher cost per diagnosis (USD 982 vs USD 871, P = .08).
      Bootstrapping suggested that 90% of incremental cost-effectiveness ratios were
      less than USD 1250. CONCLUSION: Despite the increased upfront cost of external
      loop recorders, the marked improvement in diagnostic yield offsets the cost.
      External loop recorders are an economically attractive alternative. First-line
      use of external loop recorders in patients with "community-acquired" syncope and
      presyncope should be considered to optimize diagnostic yield given its value.

PMID- 16291000
TI  - The effects of enhanced external counterpulsation on myocardial perfusion in
      patients with stable angina: a multicenter radionuclide study.
AB  - BACKGROUND: Enhanced external counterpulsation (EECP) reduces angina and extends
      time to exercise-induced ischemia in patients with symptomatic coronary disease.
      One- and two-center studies and a retrospective case series reported that EECP
      improves myocardial perfusion in stable angina pectoris. We sought to critically
      evaluate and quantify the effect of EECP on myocardial perfusion. METHODS: In 6
      US university hospitals, EECP was performed for 35 hours in patients with class
      II to IV angina who had exercise-induced myocardial ischemia. Symptom-limited
      quantitative gated technetium Tc 99m sestamibi single photon emission computed
      tomography exercise perfusion imaging was performed at baseline and 1 month post
      EECP. Sestamibi was injected at the same heart rate in both stress tests. Single
      photon emission computed tomography images were read at a blinded core
      laboratory. RESULTS: Thirty-seven patients were enrolled, 34 of whom completed
      pre- and post-EECP stress testing. The mean age was 61 +/- 10 years, 81% were
      male, 78% had prior revascularization, and 68% had 3-vessel disease. The mean
      angina class decreased from 2.7 +/- 0.7 at baseline to 1.7 +/- 0.7 after EECP (P
      < .001). Exercise duration increased from 9.1 +/- 3.7 minutes at baseline to 10.2
      +/- 3.6 minutes post-EECP (P = .03). The average percentage of tracer uptake,
      magnitude of reversibility, average thickening fraction, and the left ventricular
      ejection fraction remained unchanged after EECP. CONCLUSIONS: We confirm previous
      report that EECP reduces angina and improves exercise capacity. There were no
      significant changes in mean defect magnitude, amount of reversibility, thickening
      fraction, and ejection fraction measured using myocardial quantitative single
      photon emission computed tomography imaging when compared at identical pre- and
      post-EECP heart rates.

PMID- 16291001
TI  - Screening for coronary artery disease in patients with diabetes: a Bayesian
      strategy of clinical risk evaluation and exercise echocardiography.
AB  - OBJECTIVE: Screening for coronary artery disease is constrained by its low
      prevalence in unselected patients. We compared the ability of clinical scores to
      identify a high-risk group with diabetes mellitus and investigated a Bayesian
      strategy by combination with exercise echocardiography (ExE). METHODS: The
      Framingham risk score (FRS), a score based on the American Diabetes Association
      (ADA) screening guidelines, the United Kingdom Prospective Diabetes Study (UKPDS)
      risk engine, and a disease-specific diabetic cardiac risk score (DCRS) were
      calculated in 199 asymptomatic patients with type 2 diabetes mellitus undergoing
      ExE. The frequency of abnormal ExE and the proportion of these with coronary
      stenoses were sought in groups designated as high risk on the basis of optimal
      cutoffs for each score. All patients were followed up for 1 year. RESULTS: High
      risk was identified in fewer patients with the DCRS (27%) than FRS (38%, P =
      .02), ADA (41%, P = .004), and UKPDS (43%, P = .001). Exercise echocardiography
      was positive in 27 (14%); 11 of 23 proceeding to angiography showed significant
      stenoses. Areas under the receiver operator characteristic curves for prediction
      of a positive ExE were similar for DCRS, UKPDS, and FRS but less for ADA (P =
      .04). Positive ExE was uncommon in low-risk patients (8%-11%) and most were false
      positives (58%-80%). Cardiovascular events (n = 9) were more likely in the high
      risk compared with the low-risk UKPDS (9% vs 2%, P = .03) and DCRS (12% vs 2%, P
      = .01). CONCLUSION: Combination of the UKPDS or DCRS with ExE may optimize
      detection of coronary artery disease and cardiac events in asymptomatic patients,
      while minimizing the numbers of ExE and false-positive rate.

PMID- 16291002
TI  - Ultrasound-detected carotid plaque as a screening tool for advanced subclinical
      atherosclerosis.
AB  - BACKGROUND: There is great need for a simple, noninvasive tool that can be used
      in an office setting to screen for subclinical atherosclerosis. In patients
      referred for cardiovascular (CV) risk assessment, we evaluated the ability of
      ultrasound screening for carotid plaque to identify patients with advanced
      subclinical atherosclerosis. METHODS: Consecutive asymptomatic patients without
      vascular disease referred by their physician for measurement of the ankle
      brachial pressure index and carotid intima-media thickness (CIMT) were included.
      Carotid intima-media thickness was measured using the standardized ultrasound
      protocol from the Atherosclerosis Risk in Communities (ARIC) study. Advanced
      atherosclerosis was defined as CIMT > or = 75th percentile for age, sex, and race
      in ARIC. RESULTS: The mean age of the 327 subjects was 55.4 years (SD 7.7 years).
      The 10-year Framingham CV risk was 5.1% (4.8%). In a multiple logistic regression
      model that included Framingham CV risk, ankle-brachial pressure index, and use of
      lipid-lowering medications, plaque presence significantly predicted advanced
      atherosclerosis (odds ratio 3.08, 95% CI 1.91-4.96, P < .001). In stepwise
      regression models that included age, body mass index, current tobacco use, family
      history of premature CV disease, fasting glucose, sex, systolic blood pressure,
      total/high-density lipoprotein cholesterol ratio, and use of antihypertensive and
      lipid-lowering medications, plaque presence independently predicted advanced
      atherosclerosis (P < .001). CONCLUSION: Ultrasound detection of carotid plaque
      helped identify asymptomatic patients with advanced subclinical atherosclerosis.
      Screening for carotid plaque is easier than determination of CIMT and may help
      detect asymptomatic patients at increased CV risk.

PMID- 16291003
TI  - The use and effect of surgical therapy for prosthetic valve infective
      endocarditis: a propensity analysis of a multicenter, international cohort.
AB  - BACKGROUND: Although surgical intervention is often used in the treatment of
      prosthetic valve infective endocarditis (PVIE), an understanding of its effect on
      survival has been limited by the biases of observational studies and lack of
      controlled trials. METHODS: The International Collaboration on Endocarditis
      Merged Database is a large, multicenter, international registry of patients with
      definite endocarditis by Duke criteria, including 367 patients with PVIE.
      Clinical, microbiologic, and echocardiographic variables were analyzed to
      determine those factors associated with the use of surgery for PVIE. Logistic
      regression analysis was performed to create a propensity model of predictors of
      surgery use. Patients who underwent surgery during initial hospitalization were
      matched by propensity score with patients treated with medical therapy alone.
      Logistic regression analysis was performed to determine variables independently
      associated with inhospital mortality in this matched subset. RESULTS: Surgical
      therapy for PVIE was performed in 148 (42%) of 367 patients. Inhospital mortality
      was similar for patients treated with surgery compared with those treated with
      medical therapy alone (25.0% vs 23.4%, P = .729). Surgical therapy was
      independently associated with patient age, microorganism, intracardiac abscess,
      and congestive heart failure. After adjustment for these determinants, inhospital
      mortality was predicted by brain embolization (OR 11.12, 95% CI 4.16-29.73) and
      Staphylococcus aureus infection (OR 3.67, 95% CI 1.29-9.74), with a trend toward
      benefit for surgery (OR 0.56, 95% CI 0.23-1.36). CONCLUSIONS: Despite the
      frequent use of surgery for the treatment of PVIE, this condition continues to be
      associated with a high inhospital mortality rate in the contemporary era. After
      adjustment for factors related to surgical intervention, brain embolism and S
      aureus infection were independently associated with inhospital mortality and a
      trend toward a survival benefit of surgery was evident.

PMID- 16291004
TI  - Use of surgery in patients with native valve infective endocarditis: results from
      the International Collaboration on Endocarditis Merged Database.
AB  - BACKGROUND: Early surgery has been shown to be beneficial for patients with
      infective endocarditis (IE), yet surgery is not used in most patients. Evidence
      of the uncertainty around the use of surgery can be found in the wide variations
      in the use of cardiac surgery in IE with few precise indications for cardiac
      surgery yet defined. The aim of the study was to characterize patients with
      native valve IE relative to surgery and to determine if patients who benefit from
      an early surgical intervention can be identified. METHODS: The International
      Collaboration on Endocarditis Merged Database was used to quantify the
      differences between patients with IE receiving medical and surgical intervention
      in 1516 patients with definite native valve IE. Propensity models were built to
      identify a group of patients that benefit from early surgery. RESULTS: Patients
      in the early surgical group were more likely to be male, younger, and with less
      comorbidities compared with the early medical group (P < .001 for all) and were
      less likely to have infection with Staphylococcus aureus or viridans group
      streptococci (P < .05 for all). Intracardiac abscess and heart failure were much
      more common in the surgical group (P < .001 for all). In an unadjusted
      comparison, there was no statistically significant survival advantage in the
      surgical group. However, in the propensity analysis, in the subgroup of patients
      with the most indications for surgery, there was a significant decrease in
      mortality associated with early surgery (11.2% vs 38.0%, P < .001). CONCLUSIONS:
      The benefits of surgery are not seen uniformly in all patients with native valve
      IE, but are most realized in a targeted population. This observation requires
      confirmation in other populations of patients with definite IE.

PMID- 16291005
TI  - Analysis of mortality and risk factors associated with native valve endocarditis
      in drug users: the importance of vegetation size.
AB  - BACKGROUND: Native valve endocarditis in drug-user patients had a microbiology, a
      frequency of involvement of different cardiac valves, and a prognosis that differ
      from those in non-drug users. A retrospective study of native valve endocarditis
      cases in intravenous drug users diagnosed from 1985 to 1999 in our institution
      was performed to analyze the inhospital mortality of drug users with native valve
      endocarditis and to identify factors predictive of mortality. METHODS: All
      patients fulfilled the Duke's criteria for definite or probable endocarditis.
      Analysis of predictors of inhospital mortality was restricted to right-sided
      infective endocarditis (IE) with definite diagnosis and echocardiographic data.
      The following variables were analyzed: sex, HIV serostatus, CD4 cell count <
      200/mm3, time of IE diagnosis (before 1993 or after 1993), previous valvulopathy,
      polymicrobial IE, fungal etiology (mixed or alone), neurological complication,
      arterial emboli, pulmonary emboli, congestive heart failure, vegetation size (VS)
      > 2 cm, and inhospital cardiac surgery. Logistic regression was used in a
      multivariate model to identify factors independently associated with mortality.
      Adjusted odds ratios (OR) and 95% CIs were examined. RESULTS: Four hundred ninety
      three cases of IE were diagnosed in this period. Two hundred twenty cases of
      native valve endocarditis in intravenous drug users were identified. Fourteen
      cases in this group died (6%). Mean time from diagnosis to death was 18.5 +/- 15
      days (range, 3-52). Vegetation size was available in 111 cases. Univariate
      analysis identified the following variables associated with inhospital mortality
      in right-sided cases: VS > 2 cm and fungal etiology. In multivariate analysis,
      the variables associated with mortality that achieved statistical significance
      were size of vegetation > 2 cm (P = .014, OR 10.2, 95% CI 1.6-78.0) and fungal
      etiology (P = .009, OR 46.2, 95% CI 2.4-1100.9). CONCLUSIONS: The main prognostic
      factors of inhospital mortality in right-sided IE in drug users in our series
      were VS > 2 cm and fungal etiology. The role of early surgery in these patients
      should be reevaluated.

PMID- 16291006
TI  - Effects of angiotensin-converting enzyme inhibition on mitral regurgitation
      severity, left ventricular size, and functional capacity.
AB  - BACKGROUND: Mitral regurgitation (MR) is a progressive disorder that leads to
      left ventricular (LV) dilatation and dysfunction. Previous small studies have
      shown conflicting results regarding the benefits of afterload reduction for MR.
      METHODS: We assessed by serial echocardiography the effects of ramipril on MR
      severity and LV size by a number of quantitative methods in 26 asymptomatic
      patients with moderate to severe MR at baseline and again after 6 months of
      ramipril treatment. We also evaluated exercise capacity, neurohormonal levels,
      and the Minnesota Living With Heart Failure score. RESULTS: Despite a significant
      reduction in blood pressure with ramipril, there was no change in MR severity. MR
      severity, as assessed by effective regurgitant orifice area, was reduced in
      individuals with baseline systolic blood pressure (SBP) > or = 140 mm Hg (55.1 +/
      26 vs 37.4 +/- 35.4 mm2, P = .03), but not in individuals with SBP < 140 mm Hg
      (39.7 +/- 37.7 vs 46.1 +/- 34.1 mm2, P = not significant). Neither LV cavity
      size, exercise capacity, nor the Minnesota Living With Heart Failure score
      exhibited a significant change. CONCLUSIONS: Patients with MR do not experience
      significant changes in MR severity, LV size, or functional status after 6 months
      of treatment with angiotensin-converting enzyme inhibition. However, patients
      with SBP > or = 140 mm Hg represent a subgroup that shows reduction in MR. These
      data are consistent with current American College of Cardiology/American Heart
      Association guidelines, which reserve the use of afterload reduction for MR
      patients with systemic hypertension or LV dysfunction.

PMID- 16291008
TI  - Reducing residual risk for patients on statin therapy: the potential role of
      combination therapy.
AB  - Cholesterol-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitors, or statins, has been established as an effective method of
      reducing death and myocardial infarction among patients with coronary artery
      disease (CAD). However, a significant number of patients receiving statin therapy
      continue to have high residual risk. An important clinical challenge exists in
      reducing residual CAD risk with optimal therapies without increasing adverse
      effects. Combination therapy appears most appropriate for patients with a high
      rate of events of residual risk despite optimal statin therapy. This article
      discusses the role of combination therapy in managing CAD and in achieving
      optional targets in high-risk patient populations.

PMID- 16291009
TI  - Rationale for targeting multiple lipid pathways for optimal cardiovascular risk
      reduction.
AB  - Clinical trials of statin therapy have consistently demonstrated significant
      reductions in coronary artery disease (CAD) events, yet statin-treated patients
      remain at risk for CAD despite substantial reductions in low-density lipoprotein
      (LDL) cholesterol. Recent evidence from clinical trials supports reduction of LDL
      cholesterol to lower targets, and the updated treatment guidelines include
      optional, more aggressive LDL cholesterol goals for patients at very high and
      moderately high risk. Achievement of these lower goals will require enhanced
      treatment strategies. Targeting multiple lipid pathways can provide greater
      reductions in LDL cholesterol as well as improvements in other lipid parameters.
      Clinical trials are needed to determine which treatment strategies provide
      optimal cardiovascular risk reduction.

PMID- 16291010
TI  - Modifying plasma low-density lipoprotein and high-density lipoprotein
      cholesterol: what combinations are available in the future?
AB  - Despite a growing body of research on the benefit of combination drug therapy for
      dyslipidemia in the metabolic syndrome or diabetes mellitus, there are
      insufficient outcome data on the use of combination therapy as well as inadequate
      data to compare certain combination regimens. The focus of the therapeutic
      approach in treating the metabolic syndrome has been almost exclusively on low
      density lipoprotein (LDL) cholesterol for approximately the past 10 years, and
      specifically on statin therapy. Although results of epidemiologic studies as well
      as clinical trials using angiographic and clinical end points confirm the
      association of LDL cholesterol and risk of coronary artery disease, data are
      lacking regarding the effects of combination therapy in the management of
      coronary artery disease. Management of the metabolic syndrome focusing on the
      modification of plasma LDL as well as high-density lipoprotein cholesterol is
      reviewed. Future management strategies with the use of novel combination therapy
      is also discussed.

PMID- 16291011
TI  - Fixed combination drugs for cardiovascular disease risk reduction: regulatory
      approach.
AB  - The use of combination drug therapy for cardiovascular (CV) disease risk
      reduction is the established approach to multiple risk factor reduction. The
      spectrum of rational combination products in CV disease prevention and treatment
      alone is extremely broad. Development of fixed-dose combination drug products
      requires information beyond that needed for approval of single active ingredient
      products. Establishing the rationale and target populations for novel
      combinations, as well as the contributions of the component drugs to the claimed
      effects, and characterizing the pharmacokinetics, the pharmacodynamics, and
      clinical safety and efficacy of the combination are all necessary to support
      approval.

PMID- 16291013
TI  - Assessment of reaching goal in patients with combined hyperlipidemia: low-density
      lipoprotein cholesterol, non-high-density lipoprotein cholesterol, or
      apolipoprotein B.
AB  - It is well established that patients with combined hyperlipidemia, defined as
      elevated triglyceride levels between 200 and 500 mg/dL and elevated low-density
      lipoprotein cholesterol >130 mg/dL, are at increased risk for coronary artery
      disease. The optimal assessment of reaching lipid goals in patients with combined
      hyperlipidemia is still far from settled and has been an area of revision and
      modification in recent guidelines. Although controversy remains as to the best
      single measurement to be used in treatment goals, current focus is on the use of
      low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol,
      and apolipoprotein B. This article reviews the use of these 3 biomarkers in
      assessing cardiovascular risk, and the strategies for managing combined
      hyperlipidemia.

PMID- 16291014
TI  - Pharmacokinetic interactions between statins and fibrates.
AB  - Concomitant use of a fibrate and a statin may offer a therapeutic advantage to
      patients with dyslipidemia, especially in patients whose low-density lipoprotein
      cholesterol is controlled by statins but whose high-density lipoprotein
      cholesterol or triglycerides, or both, are not within goal. However, concern
      about drug-drug interactions may preclude optimal use of combination statin
      fibrate therapy. This article reviews the pharmacokinetics between statins and
      fibrates, addressing risks associated with drug-drug interactions and combination
      therapy.

PMID- 16291015
TI  - High-density lipoprotein as a therapeutic target: clinical evidence and treatment
      strategies.
AB  - The clinical importance of low serum levels of high-density lipoprotein (HDL)
      cholesterol is often under-recognized and underappreciated as a risk factor for
      premature atherosclerosis as well as for cardiovascular morbidity and mortality.
      Low serum levels of HDL are frequently encountered, especially in patients who
      are obese or have the metabolic syndrome. In prospective epidemiologic studies,
      every 1-mg/dL increase in HDL is associated with a 2% to 3% decrease in coronary
      artery disease risk, independent of low-density lipoprotein (LDL) cholesterol and
      triglyceride (TG) levels. The primary mechanism for this protective effect is
      believed to be reverse cholesterol transport, but several other anti
      inflammatory, antithrombotic, and antiproliferative functions for HDL have also
      been identified. In recognition of these antiatherogenic effects, recent
      guidelines have increased the threshold for defining low levels of HDL for both
      men and women. The first step in achieving these revised targets is therapeutic
      lifestyle changes. When these measures are inadequate, pharmacotherapy specific
      to the patient's lipid profile should be instituted. Niacin therapy, currently
      the most effective means for raising HDL levels, should be initiated in patients
      with isolated low HDL (HDL <40 mg/dL, LDL and non-HDL at or below National
      Cholesterol Education Program (NCEP) targets based on global cardiovascular risk
      evaluation). Patients who have both low HDL and elevated LDL should receive a
      statin or statin-niacin combination therapy, and patients with concomitant low
      HDL and elevated TGs should receive a fibrate initially, with a statin, niacin,
      or ezetimibe added thereafter as needed to help attain NCEP lipoprotein targets.

PMID- 16291016
TI  - Non-high-density lipoprotein cholesterol: the forgotten therapeutic target.
AB  - The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP
      III) has acknowledged mounting evidence of an independent association between
      hypertriglyceridemia and coronary artery disease risk by issuing guidelines that
      identify non-high-density lipoprotein (HDL) cholesterol as a secondary target for
      therapy in patients with elevated triglyceride levels. In 2003, a national survey
      of outpatient lipid management was conducted for patients undergoing treatment by
      physicians who were high prescribers of lipid-altering drugs. Results of the NCEP
      Evaluation Project Utilizing Novel E-Technology II (NEPTUNE II) survey indicated
      much higher frequencies of low-density lipoprotein (LDL) cholesterol goal
      achievement compared with frequencies observed in a similarly designed survey in
      1997. However, non-HDL cholesterol treatment success in the NEPTUNE II survey was
      markedly lower than that for LDL cholesterol overall and across risk categories.
      More aggressive therapy is therefore needed to achieve non-HDL cholesterol goals
      than LDL cholesterol goals. After achievement of LDL cholesterol goals, non-HDL
      cholesterol can be managed more aggressively by lowering LDL cholesterol or by
      using strategies that target a reduction in very-low-density lipoprotein
      cholesterol. Because the prevalence of hypertriglyceridemia in the United States
      is high and increasing, enhanced efforts to improve non-HDL cholesterol goal
      achievement have the potential to produce a substantial effect on public health.

PMID- 16291017
TI  - Pharmacogenomics of statin responsiveness.
AB  - Statins are widely prescribed and are established as first-line therapy for the
      primary and secondary prevention of coronary artery disease. However, the benefit
      of treatment varies between patients. Genetic variation can contribute to
      interindividual variations in clinical efficacy of drug therapy, and significant
      progress has been made in identifying common genetic polymorphisms that influence
      responsiveness to statin therapy. To date, >30 candidate genes related to
      pharmacokinetics and pharmacodynamics of statins have been investigated as
      potential determinants of drug responsiveness in terms of low-density lipoprotein
      cholesterol lowering. Genetic variation at gene loci that affect intestinal
      cholesterol absorption include apolipoprotein (apo) E; adenosine triphosphate
      binding cassette transporter G5 and G8; cholesterol production, such as 3-hydroxy
      3-methylglutaryl coenzyme A reductase; and lipoprotein catabolism, such as apoB
      and the low-density lipoprotein receptor, all may play a role in modulating
      responsivesness as well genes involved in metabolism of statins such as
      cytochrome P450. However, there is considerable variation in results reported,
      and the data suggest that combined analysis of multiple genetic variants in
      several genes, all of which have possible functional significance, is more likely
      to give significant results than single gene studies in small sample populations.
      In the future, pharmacogenomic studies with a greater number of participants
      (>2,000 participants) should provide a better picture as to who is most likely
      and who is least likely to benefit from statin therapy.

PMID- 16291018
TI  - Distinguishing neural substrates of heterogeneity among anxiety disorders.

PMID- 16291019
TI  - Neuroimaging in dementia.

PMID- 16291020
TI  - Prefrontal and anterior cingulate contributions to volition in depression.

PMID- 16291021
TI  - Functional imaging research in schizophrenia.

PMID- 16291022
TI  - Neuroimaging in functional somatic syndromes.

PMID- 16291023
TI  - Neuroimaging in multiple sclerosis.

PMID- 16291024
TI  - Stroke.

PMID- 16291025
TI  - Functional MRI in pediatric neurobehavioral disorders.

PMID- 16291027
TI  - Neuroimaging and human genetics.

PMID- 16291026
TI  - Structural MRI and brain development.

PMID- 16291028
TI  - Neuroreceptor imaging in psychiatry: theory and applications.

PMID- 16291032
TI  - Erectile dysfunction and cardiovascular risk factors.
AB  - There are numerous causes of erectile dysfunction (ED), including psychogenic,
      organic,and mixed psychogenic/organic. Among the organic causes the most common
      include vascular, neurogenic, endocrine, structural, drug-induced, and others.
      Some have estimated that nearly one half of all causes of ED in men over 50 years
      of age are vascular in nature. This article reviews cardiovascular risk factors
      of ED.

PMID- 16291033
TI  - Epidemiology of erectile dysfunction: the role of medical comorbidities and
      lifestyle factors.
AB  - Erectile dysfunction (ED) is a highly prevalent condition in aging men with
      significant interpersonal and psychosocial consequences. Large-scale
      epidemiologic studies have demonstrated a consistent age-related loss of erectile
      function in men from different geographic and ethnic backgrounds, with
      approximately half of men over 70 years of age reporting moderate to severe
      symptoms. ED is associated strongly with specific comor-bidities, such as
      cardiovascular disease and hypertension, diabetes mellitus, lower urinary tract
      symptoms, prostate cancer, and depression. Lifestyle factors, including obesity
      and exercise frequency, also have been implicated in recent studies.

PMID- 16291031
TI  - Physiology of penile erection and pathophysiology of erectile dysfunction.
AB  - This article reviews the physiology of penile erection, the components of
      erectile function, and the pathophysiology of erectile dysfunction. The molecular
      and clinical under-standing of erectile function continues to gain ground at a
      particularly fast rate. Advances in gene discovery have aided greatly in working
      knowledge of smooth muscle relaxation/contraction pathways. The understanding of
      the nitric oxide pathway has aided not only in the molecular understanding of the
      tumescence but also greatly in the therapy of erectile dysfunction.

PMID- 16291034
TI  - Phosphodiesterase-5 inhibition: the molecular biology of erectile function and
      dysfunction.
AB  - This article discusses the role of phosphodiesterase-5 (PDE-5) inhibition in the
      molecular biology of erectile function and dysfunction. Commercially marketed PDE
      5 inhibitors are highly specific for PDE-5, and in the face of continuing cyclic
      GMP (cGMP) synthesis,elevate cellular cGMP. This elevation results from direct
      competitive inhibition of PDE-5 and from blocking the negative feedback
      regulation of the enzyme. Elevation of cGMP activates cGMP-dependent protein
      kinase, which mediates the effects of the cGMP-signaling pathway to decrease
      smooth muscle tone and dilate penile vascular smooth muscle. By exploiting
      features of PDE-5 regulatory mechanisms that modulate PDE-5 function, the
      inhibitors enhance their own potencies.

PMID- 16291035
TI  - Psychosocial evaluation and combination treatment of men with erectile
      dysfunction.
AB  - The Sexual Tipping Point forms the foundation of a biopsychosocial model to help
      conceptualize a combination treatment, where sex coaching and sexual
      pharmaceuticals are integrated into a clinical approach, which addresses organic,
      psychologic, and cultural issues for men with erectile dysfunction (ED). At any
      moment in the intervention pro-cess, the clinician determines the most elegant
      solution, which focuses the majority of effort on fixing the predominant factor
      while not ignoring the others. Clinicians using this model, can fully
      conceptualize ED by understanding the predisposing, precipitating,and maintaining
      psychosocial aspects of their patient's diagnosis and management, as well as
      organic causes and risk factors. The sex status or focused sex history, and
      continuous reassessment based on follow-up are the core elements of this method.
      Restoration of lasting and satisfying sexual function requires a multidimensional
      understanding of all of the forces that created the dysfunction, whether a solo
      clinician or multidisciplinary team approach is used. Each clinician needs to
      carefully evaluate their own competence and interests when considering the
      treatment of a man's ED, so that regardless of the modality used, the patient
      receives optimized care to restore sexual function and satisfaction.

PMID- 16291036
TI  - Clinical evaluation of erectile dysfunction in the era of PDE-5 inhibitors.
AB  - Erectile dysfunction (ED) is a common disorder that has gained attention since
      the introduction of relatively safe treatment with phosphodiesterase-5
      inhibitors. ED is a multi-factorial disorder and a common presentation for
      several systemic illnesses,particularly vascular occlusive diseases. The clinical
      evaluation of ED should be thorough and systematic, with attention to the
      appropriate use of sexual symptom questionnaires and symptom scales, detailed
      medical and sexual history, physical examination,and basic screening laboratory
      tests. Patients should be referred for specialized evaluations when appropriate.
      The clinician must be familiar with the pathophysiologic mechanisms of ED, its
      associations with other systemic diseases, the indications for specialist
      referrals, and the role of specialized testing to diagnose and treat this
      disorder effectively.

PMID- 16291037
TI  - Androgen deficiency in the etiology and treatment of erectile dysfunction.
AB  - The evaluation and management of erectile dysfunction (ED) has evolved
      dramatically following the introduction of oral phosphodiesterase-5 inhibitors.
      Despite the limited role of directed diagnostic testing in the evaluation of the
      impotent patient, routine de-termination of a serum testosterone likely is
      indicated based on evidence that testosterone modulates erectile function, that
      hypogonadism is prevalent among elderly men and men with ED, and that
      symptomatology alone rarely detects hypogonadism. Forms of testosterone commonly
      used include oral, parenteral, transdermal, and implantable preparations, each
      with significant advantages and disadvantages. The risks and benefits of
      testosterone supplementation have been characterized incompletely and will
      require further validation before widespread use of testosterone as hormone
      replacement therapy in aging men.

PMID- 16291038
TI  - Peyronie's disease: etiology, epidemiology and medical treatment.
AB  - The investigation of medical options for the treatment of Peyronie's disease is
      lacking controlled clinical trials with uniform standardized assessments and
      objective measures of deformity, including curvature and circumference. A key to
      defining the beneficial effects of various medical therapies lies in
      standardizing the evaluation of the Peyronie's patient across various studies so
      that the proposed benefits can be confirmed and applied to all populations.
      Furthermore, basic science research into the pathophysiology of this disorder is
      likely to yield new insights into potential treatment options and direct future
      therapies.

PMID- 16291039
TI  - Surgical treatment of Peyronie's disease.
AB  - Peyronie's Disease (PD) is a sexually debilitating disease resulting in
      significant psycho-logic stress for many men. Urologists have an opportunity to
      help men suffering from PD to improve their lives. Appropriate treatment should
      be individualized and tailored to the patient's expectations, disease history,
      physical examination findings, and erectile function. This review is intended to
      share the experiences of other urologists in the surgical approach to PD.

PMID- 16291040
TI  - Central nervous system agents in the treatment of erectile dysfunction.
AB  - In the last two decades, a better understanding of the mechanisms governing
      erectile function and the pathophysiologies underlying erectile dysfunction (ED)
      have led re-searchers to investigate novel treatment concepts. Selective type-5
      phosphodiesterase inhibitors are recommended as first-line therapy because of
      their high efficacy, but 30% to 40% of patients who have ED do not respond
      adequately to these agents and require alternative methods. The central nervous
      system plays a fundamental role in sexual behavior. Animal models have advanced
      our understanding of the neuroanatomic and neuropharmacologic basis of centrally
      induced penile erections. Clinical research with apomorphine has demonstrated
      efficacy in men who have a range of ED. Recent interest has focused on other
      centrally acting agents for ED treatment, including the melanocortin receptor
      agonists.

PMID- 16291041
TI  - Penile prosthesis implantation: surgical implants in the era of oral medication.
AB  - In patients who are not satisfied with the results of oral agents
      (phosphodiesterase-5 inhibitors) or in whom oral agents or other medical
      treatment fails to produce an adequate response, penile prosthesis implantation
      is an excellent treatment modality for restoring erectile function.
      Patient/partner acceptance, use, and satisfaction rates of penile pros-theses are
      better than for many other alternatives including pharmacologic injections. In
      flatable penile prostheses are most frequently used and have the highest
      satisfaction rates. Complications of these multipiece prostheses continue to
      decline, and patient satisfaction rates, tolerability, and longevity continue to
      increase.

PMID- 16291042
TI  - PDE-5 inhibitors: current status and future trends.
AB  - Phosphodiesterase-5 (PDE-5) inhibitors are a well-established, first-line therapy
      for erectile dysfunction (ED). Extensive clinical trials and clinical experience
      established the highly significant efficacy and the safety of this class of drugs
      in the treatment of ED.Furthermore, the efficacy of PDE-5 inhibitors has been
      established in men with ED with a broad range of etiologies and comorbidities.
      The future of PDE-5 inhibitors includes the expansion of indications such as the
      treatment of pulmonary hypertension and the potential of treatment of symptomatic
      BPH.

PMID- 16291044
TI  - Putting feet first in diabetes.

PMID- 16291043
TI  - Herceptin and early breast cancer: a moment for caution.

PMID- 16291045
TI  - A forecast of disaster for Pakistan.

PMID- 16291046
TI  - Causes of diabetic foot lesions.

PMID- 16291047
TI  - Preventing foot ulcers and amputations in diabetes.

PMID- 16291048
TI  - Barriers to the delivery of diabetic foot care.

PMID- 16291049
TI  - Folate supplementation and cardiovascular disease.

PMID- 16291050
TI  - More men (and women) on the Moon?

PMID- 16291051
TI  - Lois Jovanovic: giving hope to diabetic mothers.

PMID- 16291052
TI  - Gangrene.

PMID- 16291054
TI  - California's prison health system.

PMID- 16291055
TI  - California's prison health system.

PMID- 16291056
TI  - Recurring policy errors: blind spots over cataracts.

PMID- 16291057
TI  - Building trust or buying results?

PMID- 16291059
TI  - Combination antibiotic susceptibility testing in cystic fibrosis.

PMID- 16291061
TI  - Treatment of depression in children and adolescents.

PMID- 16291062
TI  - Ertapenem versus piperacillin/tazobactam for diabetic foot infections (SIDESTEP):
      prospective, randomised, controlled, double-blinded, multicentre trial.
AB  - BACKGROUND: Diabetic foot infections are a common and serious problem, yet few
      randomised trials of adequate quality have compared the efficacy of the various
      antibiotic regimens available for their treatment. Our aim was to assess the
      efficacy and safety of ertapenem versus piperacillin/tazobactam for foot
      infections. METHODS: We did a randomised, double-blinded, multicentre trial in
      adults (n=586) with diabetes and a foot infection classified as moderate-to
      severe and requiring intravenous antibiotics. We assigned patients intravenous
      ertapenem (1 g daily; n=295) or piperacillin/tazobactam (3.375 g every 6 h;
      n=291) given for a minimum of 5 days, after which oral amoxicillin/clavulanic
      acid (875/125 mg every 12 h) could be given for up to 23 days. Investigators
      retained the option to administer vancomycin to patients in either group to
      ensure adequate coverage for potentially antibiotic resistant Enterococcus spp
      and meticillin-resistant Staphylococcus aureus (MRSA). Our primary outcome was
      the proportion of patients with a favourable clinical response (cure or
      improvement) on the day that intravenous antibiotic was discontinued. Analyses
      were by an evaluable-patient only approach. This study is registered with ,
      number NCT00229112. FINDINGS: Of the 576 patients treated, 445 were available for
      assessment at the end of intravenous therapy. Both baseline characteristics and
      favourable clinical response rates were similar for the 226 who received
      ertapenem and the 219 who received piperacillin/tazobactam (94%vs 92%,
      respectively; between treatment difference 1.9%, 95% CI -2.9 to 6.9). Rates of
      favourable microbiological responses (eradication rates and clinical outcomes, by
      pathogen) and adverse events did not differ between groups. INTERPRETATION:
      Clinical and microbiological outcomes for patients treated with ertapenem were
      equivalent to those for patients treated with piperacillin/tazobactam, suggesting
      that this once-daily antibiotic should be considered for parenteral therapy of
      diabetic foot infections, when deemed appropriate.

PMID- 16291063
TI  - Negative pressure wound therapy after partial diabetic foot amputation: a
      multicentre, randomised controlled trial.
AB  - BACKGROUND: Diabetic foot wounds, particularly those secondary to amputation, are
      very complex and difficult to treat. We investigated whether negative pressure
      wound therapy (NPWT) improves the proportion and rate of wound healing after
      partial foot amputation in patients with diabetes. METHODS: We enrolled 162
      patients into a 16-week, 18-centre, randomised clinical trial in the USA.
      Inclusion criteria consisted of partial foot amputation wounds up to the
      transmetatarsal level and evidence of adequate perfusion. Patients who were
      randomly assigned to NPWT (n=77) received treatment with dressing changes every
      48 h. Control patients (n=85) received standard moist wound care according to
      consensus guidelines. NPWT was delivered through the Vacuum Assisted Closure
      (VAC) Therapy System. Wounds were treated until healing or completion of the 112
      day period of active treatment. Analysis was by intention to treat. This study
      has been registered with , number NCT00224796. FINDINGS: More patients healed in
      the NPWT group than in the control group (43 [56%] vs 33 [39%], p=0.040). The
      rate of wound healing, based on the time to complete closure, was faster in the
      NPWT group than in controls (p=0.005). The rate of granulation tissue formation,
      based on the time to 76-100% formation in the wound bed, was faster in the NPWT
      group than in controls (p=0.002). The frequency and severity of adverse events
      (of which the most common was wound infection) were similar in both treatment
      groups. INTERPRETATION: NPWT delivered by the VAC Therapy System seems to be a
      safe and effective treatment for complex diabetic foot wounds, and could lead to
      a higher proportion of healed wounds, faster healing rates, and potentially fewer
      re-amputations than standard care.

PMID- 16291064
TI  - Early changes in the skin microcirculation and muscle metabolism of the diabetic
      foot.
AB  - BACKGROUND: Changes in the large vessels and microcirculation of the diabetic
      foot are important in the development of foot ulceration and subsequent failure
      to heal existing ulcers. We investigated whether oxygen delivery and muscle
      metabolism of the lower extremity were factors in diabetic foot disease. METHODS:
      We studied 108 patients (21 control individuals who did not have diabetes, 36
      patients with diabetes who did not have neuropathy, and 51 patients with both
      diabetes and neuropathy). We used medical hyperspectral imaging (MHSI) to
      investigate the haemoglobin saturation (S(HSI)O2; % of oxyhaemoglobin in total
      haemoglobin [the sum of oxyhaemoglobin and deoxyhaemoglobin]) in the forearm and
      foot; we also used 31P-MRI scans to study the cellular metabolism of the foot
      muscles by measuring the concentrations of inorganic phosphate and
      phosphocreatine and calculating the ratio of inorganic phosphate to
      phosphocreatine (Pi/PCr). FINDINGS: The forearm S(HSI)O2 during resting was
      different in all three groups, with the highest value in controls (mean 42 [SD
      17]), followed by the non-neuropathic (32 [8]) and neuropathic (28 [8]) groups
      (p<0.0001). In the foot at resting, S(HSI)O2 was higher in the control (38 [22])
      and non-neuropathic groups (37 [12]) than in the neuropathic group (30 [12];
      p=0.027). The Pi/PCr ratio was higher in the non-neuropathic (0.41 [0.10]) and
      neuropathic groups (0.58 [0.26]) than in controls (0.20 [0.06]; p<0.0001).
      INTERPRETATION: Our results indicate that tissue S(HSI)O2 is reduced in the skin
      of patients with diabetes, and that this impairment is accentuated in the
      presence of neuropathy in the diabetic foot. Additionally, energy reserves of the
      foot muscles are reduced in the presence of diabetes, suggesting that
      microcirculation could be a major reason for this difference.

PMID- 16291065
TI  - The diabetic foot in Iraq.

PMID- 16291066
TI  - The global burden of diabetic foot disease.
AB  - Diabetic foot problems are common throughout the world, resulting in major
      economic consequences for the patients, their families, and society. Foot ulcers
      are more likely to be of neuropathic origin, and therefore eminently preventable,
      in developing countries, which will experience the greatest rise in the
      prevalence of type 2 diabetes in the next 20 years. People at greatest risk of
      ulceration can easily be identified by careful clinical examination of the feet:
      education and frequent follow-up is indicated for these patients. When assessing
      the economic effects of diabetic foot disease, it is important to remember that
      rates of recurrence of foot ulcers are very high, being greater than 50% after 3
      years. Costing should therefore include not only the immediate ulcer episode, but
      also social services, home care, and subsequent ulcer episodes. A broader view of
      total resource use should include some estimate of quality of life and the final
      outcome. An integrated care approach with regular screening and education of
      patients at risk requires low expenditure and has the potential to reduce the
      cost of health care.

PMID- 16291067
TI  - Treatment for diabetic foot ulcers.
AB  - People with diabetes develop foot ulcers because of neuropathy (sensory, motor,
      and autonomic deficits), ischaemia, or both. The initiating injury may be from
      acute mechanical or thermal trauma or from repetitively or continuously applied
      mechanical stress. Patients with clinically significant limb ischaemia should be
      assessed by a vascular surgeon to determine the need for angioplasty, stenting,
      or femorodistal bypass. When infection complicates a foot ulcer, the combination
      can be limb or life-threatening. Infection is defined clinically, but wound
      cultures reveal the causative pathogens. Tissue specimens are strongly preferred
      to wound swabs for wound cultures. Antimicrobial therapy should be guided by
      culture results, and should aim to cure the infection, not to heal the wound.
      Alleviation of the mechanical load on ulcers (off-loading) should always be a
      part of treatment. Neuropathic ulcers typically heal in 6 weeks with total
      contact casting, because it effectively relieves pressure at the ulcer site and
      enforces patient compliance. The success of other approaches to off-loading
      similarly depends on the patients' adherence to the effectiveness of pressure
      relief. Surgery to heal ulcers and prevent recurrence can include tenotomy,
      tendon lengthening, reconstruction, or removal of bony prominences. However,
      these procedures may result in secondary ulceration and other complications.
      Ulcer recurrence rates are high, but appropriate education for patients, the
      provision of posthealing footwear, and regular foot care can reduce rates of re
      ulceration.

PMID- 16291068
TI  - Wound healing and its impairment in the diabetic foot.
AB  - Optimum healing of a cutaneous wound requires a well-orchestrated integration of
      the complex biological and molecular events of cell migration and proliferation,
      and of extracellular matrix deposition and remodelling. Cellular responses to
      inflammatory mediators, growth factors, and cytokines, and to mechanical forces,
      must be appropriate and precise. However, this orderly progression of the healing
      process is impaired in chronic wounds, including those due to diabetes. Several
      pathogenic abnormalities, ranging from disease-specific intrinsic flaws in blood
      supply, angiogenesis, and matrix turnover to extrinsic factors due to infection
      and continued trauma, contribute to failure to heal. Yet, despite these
      obstacles, there is increasing cause for optimism in the treatment of diabetic
      and other chronic wounds. Enhanced understanding and correction of pathogenic
      factors, combined with stricter adherence to standards of care and with
      technological breakthroughs in biological agents, is giving new hope to the
      problem of impaired healing.

PMID- 16291069
TI  - Responding to the threat of chronic diseases in India.
AB  - At the present stage of India's health transition, chronic diseases contribute to
      an estimated 53% of deaths and 44% of disability-adjusted life-years lost.
      Cardiovascular diseases and diabetes are highly prevalent in urban areas. Tobacco
      related cancers account for a large proportion of all cancers. Tobacco
      consumption, in diverse smoked and smokeless forms, is common, especially among
      the poor and rural population segments. Hypertension and dyslipidaemia, although
      common, are inadequately detected and treated. Demographic and socioeconomic
      factors are hastening the health transition, with sharp escalation of chronic
      disease burdens expected over the next 20 years. A national cancer control
      programme, initiated in 1975, has established 13 registries and increased the
      capacity for treatment. A comprehensive law for tobacco control was enacted in
      2003. An integrated national programme for the prevention and control of
      cardiovascular diseases and diabetes is under development. There is a need to
      increase resource allocation, coordinate multisectoral policy interventions, and
      enhance the engagement of the health system in activities related to chronic
      disease prevention and control.

PMID- 16291070
TI  - Malignant melanoma presenting as a foot ulcer.

PMID- 16291071
TI  - Dual role of nitric oxide in adult neurogenesis.
AB  - In the last decade, it has been demonstrated that neurogenesis persists in the
      adult mammalian brain and that it is induced after insults, where newborn neurons
      migrate to damaged areas, differentiate and contribute to the recovery. The
      understanding of the cellular and molecular events involved in this phenomenon
      could provide effective therapies not only to promote brain repair in stroke or
      seizures, but also to facilitate functional improvement in depression or
      Alzheimer. In this context, many advances have been made, such as the implication
      of different growth factors, membrane receptors, and most importantly diffusible
      messengers like nitric oxide (NO). We review here studies in both normal and
      pathophysiological conditions that suggest a dual role for NO in adult
      neurogenesis and its relation to different pharmacological strategies stimulating
      neurogenesis.

PMID- 16291072
TI  - Critical role of actin in modulating BBB permeability.
AB  - A major obstacle in the treatment of degenerative manifestations and debilitating
      diseases in the central nervous system (CNS) lies in the impediment of drug
      delivery into these tissues. The impediment is due to a membrane barrier referred
      to as the blood-brain barrier (BBB). It is known that the BBB is a unique
      membranous structure in brain capillaries that tightly segregates the brain from
      systemic blood circulation. It is imperative to have a thorough understanding of
      the molecular components and their integrated function of this barrier to develop
      effective therapeutics for CNS disorders and diseases. Although there are other
      cell and biochemical properties that underlie this barrier function, it is well
      established that the barrier is mainly made up of the physical elements of tight
      junction (TJ) complex. The major constituents of TJ, such as occludin, claudins,
      zonula occludens (ZOs) and junctional adhesion molecule (JAM) have been subjects
      of intensive studies and reviews. However, after examining currently proposed
      models, we have come to believe that a cytoskeletal component-actin may play a
      critical role in interacting TJ molecular constituents and modulating functional
      TJ complex. In this review, we will discuss the correlation of temporal and
      spatial distribution and remodeling of actin filaments with altering integrity of
      TJ complexes in various systems and present a hypothesis to depict its potential
      role in modulating BBB permeability.

PMID- 16291073
TI  - Non-antibiotic treatments for upper-respiratory tract infections (common cold).
AB  - OBJECTIVES: To review the seven Cochrane reviews of non-antibiotic treatment for
      the common cold. METHODS: Each Cochrane review was read and summarized, and
      results presented as relative risks and, where possible, numbers needed to treat.
      RESULTS: The main theme that runs through these Cochrane reviews is the variable
      quality of the primary studies. In general, the reviewers are fairly cautious
      about the benefits of any of the treatments other than first-dose decongestants
      and antihistamine-decongestant combinations. For antihistamines alone, the
      reviewers were clear about the lack of efficacy except in the high-quality
      studies in which a global improvement in symptoms was noted. Some studies were
      statistically significant, but the Cochrane reviewers were guarded about how
      clinically significant they were. For Echinacea, problems were found with the
      quality of the studies and the wide range of different forms of this substance.
      Heated humidified air seemed to be effective in the UK and Israel, but not the
      USA, making definitive statements about efficacy difficult. Over-the-counter
      medication for cough seemed to have no documented benefit in children under the
      age of 5 years. Letosteine (a mucolytic) may be effective in children but is not
      available in the UK. Bisolvon (a mucolytic) was found to be effective for cough
      in only one study. For older children and adults, dextromethorphan may be
      effective (two out of three studies showed benefit), and guiafenesin (an
      expectorant) showed mixed benefit in two trials. Dexbrompheniramine (a sedating
      antihistamine)/pseudoephedrine (6 mg/120 mg twice daily for 1 week) was
      significantly more effective than placebo for severity of cough, whereas, in
      another study, loratadine (a non-sedating antihistamine)/pseudoephedrine (5
      mg/120 mg twice daily for 4 days) did not show any difference between the study
      groups. Vitamin C may have a small role in preventing the common cold, with
      possibly a greater role in high-intensity physical activity and sub-arctic
      conditions. Zinc lozenges seemed to be effective, but the issue of unblinding due
      to taste was a methodological issue of concern to the reviewers. The benefits and
      harms are calculated as numbers needed to treat for one person to benefit (NNTB)
      and numbers needed to treat for one person to harm (NNTH), and were calculated by
      the author. CONCLUSION: Most non-antibiotic treatments for the common cold are
      probably not effective. The most promising are dextromethorphan, bisolvon and
      guiaphenesin for cough, antihistamine-decongestant combinations for a wide range
      of symptoms, nasal decongestants (at least for the first dose) and possibly zinc
      lozenges.

PMID- 16291074
TI  - Environmental tobacco smoke (ETS) exposure in children with asthma-relation
      between lead and cadmium, and cotinine concentrations in urine.
AB  - Exposure to heavy metals from environmental tobacco smoke (ETS) was investigated
      in 23 children with asthma (8.4+/-3.7 yr). ETS exposure was assessed by an
      inquiry data-based exposure index, the urinary concentration of cotinine (U
      cotinine; a major nicotine metabolite) and the house dust (fine and coarse
      fractions) concentrations of nicotine at home. The corresponding concentrations
      of the heavy metals cadmium and lead in dust and urine (U-Cd; U-Pb) were
      determined in the same samples. There were strong associations between the ETS
      exposure index and U-cotinine (r(s)=0.62; P<0.002) and nicotine in house dust
      (r(s)=0.77; P<0.001). There was a strong positive correlation between lead and
      cadmium concentrations in both fine (r(s)=0.86; P<0.001) and coarse dust
      (r(s)=0.57; P=0.02). Although, there was a tendency for a relation between
      nicotine and lead concentrations in fine dust (r(s)=0.52; P=0.06), no other
      significant associations were found between house dust metals and nicotine
      concentrations. U-Cd correlated well with U-cotinine (r(s)=0.50; P=0.02).
      Further, U-Pb were associated with U-cotinine, however not statistically
      significant (r(s)=0.41; P=0.06). A probable explanation is a direct inhalation of
      side-stream smoke containing heavy metals and/ or an increased pulmonary uptake,
      due to a small airways disease in children with asthma.

PMID- 16291075
TI  - Lack of association of human leukocyte antigen-B7 with COPD and rate of decline
      in lung function.
AB  - BACKGROUND: Although variation in the human leukocyte antigen (HLA) locus is
      associated with various diseases, there have been a limited number of studies
      that have examined the possible role of HLA in chronic obstructive pulmonary
      disease (COPD). Only HLA-B7 has been shown to be correlated with low forced
      expiratory volume in 1s (FEV1) in Caucasians; however, this finding has not been
      replicated. The aim of this study was to investigate the contribution of the HLA
      B7 allele to COPD and to rate of decline of lung function. METHODS: We determined
      the prevalence of HLA-B7 in a group of COPD patients and a non-obstructed control
      group of smokers by using a polymerase chain reaction-based genotyping assay. We
      also determined the prevalence of HLA-B7 in smokers selected from the National
      Heart Lung and Blood Institute, Lung Health Study for having the fastest and
      slowest decline of lung function. RESULTS: No significant difference was found in
      the frequency of HLA-B7 between the COPD and non-obstructed groups. There was
      also no significant association of HLA-B7 with rate of decline of lung function.
      CONCLUSION: These data indicate that HLA-B7 does not contribute to COPD or rate
      of decline of FEV1 in smokers.

PMID- 16291076
TI  - Economic evaluation of treating chronic obstructive pulmonary disease with
      inhaled corticosteroids and long-acting beta2-agonists in a health maintenance
      organization.
AB  - OBJECTIVES: In light of recent results from observational studies showing
      prolonged survival in subjects taking long-acting beta2-agonists (LABA) and/or
      inhaled corticosteroids (ICS) for chronic obstructive pulmonary disease (COPD),
      we investigated their cost-effectiveness (CE). METHODS: Costs and survival data
      were collected for a sample of members enrolled in a large Health Maintenance
      Organization in the United States. An observational study design was used to
      evaluate cumulative costs and health benefits of LABA, ICS, ICS+LABA, or
      comparison drugs. Survival was estimated using a parametric regression model.
      Costs were adjusted for censoring and prognostic factors. CE was evaluated over a
      time horizon of 36 months and the remaining lifetime of subjects. RESULTS: Over
      36 months, life expectancy and costs were: 2.4 years (95% confidence interval
      (CI): 2.3; 2.5) and $28,030 (CI: $23,400; $33,570) for not receiving ICS or LABA;
      2.6 years (CI: 2.6; 2.7) and $35,170 (CI: $29,970; $40,620) for ICS alone; 2.6
      years (CI: 2.5; 2.7) and $27,380 (CI: $21,780; $32,510) for LABA alone; and, 2.7
      years (CI: 2.6; 2.8) and $33,780 (CI: $28,700; $39,440) for subjects treated with
      ICS+LABA. The lifetime analysis showed similar trends. CONCLUSIONS: There is an
      acute need to find effective, life-extending treatments for persons with COPD.
      ICS, LABA or their combination represent promising treatment options and are
      currently being tested in randomized trials. If the impact on survival seen in
      these trials compares to that seen in observational studies, LABA and the
      combination treatment are likely to be cost-effective in the United States.

PMID- 16291077
TI  - Proposal for a multidimensional staging system for chronic obstructive pulmonary
      disease.
AB  - The severity of chronic obstructive pulmonary disease (COPD) is currently
      assessed using a single physiological measurement, the forced expiratory volume
      in 1s (FEV1). COPD, however, has complex effects on other aspects of respiratory
      function, and in many patients is associated with important systemic changes. We
      hypothesized that a multidimensional staging system for COPD could provide a more
      complete assessment of the disease's impact. We considered over 40 potential
      staging variables, evaluating them according to sensitivity to change, measured
      reproducibly, independence of the information they provide and prognostic value.
      We finally selected three: FEV1 (including arterial blood gas measurements when
      FEV1 falls below 35% predicted), Medical Research Council dyspnea scale and body
      mass index (BMI). Each measure correlates independently with prognosis in COPD,
      is supported by a significant body of literature and serves as a surrogate for
      other potentially important variables. We then used principal components analysis
      (PCA) to determine the degree of association between 30 of the potential
      variables measured in 813 stable COPD patients. Using PCA, six groups of
      measurements defined independent categories of patient information: pulmonary
      function (including FEV1), symptoms of cough and sputum, dyspnea, health status,
      bronchodilator reversibility and BMI. These include the three principal variables
      selected for the staging system. Although the staging boundaries were based on
      existing literature, they have proven useful in predicting survival. We conclude
      that a multidimensional grading system is useful to assess the impact of COPD.

PMID- 16291078
TI  - Chronic mucus hypersecretion: a marker of asthma in young adults?
AB  - OBJECTIVE: To investigate if chronic mucus hypersecretion (CMH) can be used as a
      marker of asthma in young adults. STUDY DESIGN AND SETTING: Cross-sectional study
      of a population sample of young Danish adults (n=624, 279 males), aged 19-29
      years. Case history, including tobacco exposure and respiratory symptoms, was
      obtained by questionnaire. Pulmonary function, histamine responsiveness,
      bronchodilator reversibility, skin test reactivity, and leukocyte count were
      measured using standard techniques. RESULTS: The overall prevalence of CMH was
      7.7%, 8.4% in females and 6.9% in males, respectively, of whom more than 70% were
      current smokers. The presence of CMH was significantly associated with self
      reported asthma, dyspnea at exertion, number of pack-years, lower FEV1/FVC ratio,
      and lower BMI. However, no significant association was found between CMH and the
      following asthma-related factors: airway responsiveness to inhaled histamine,
      bronchodilator reversibility, self-reported rhinitis or eczema, atopy, FEV1
      (%pred), and B-eosinophil count. CONCLUSIONS: CMH is a common finding in young
      adults, primarily in smokers. CMH was related to respiratory symptoms suggesting
      asthma, but no significant association was observed between CMH and objective
      signs of asthmatic airway lability. The present findings therefore may suggest
      that CMH is likely to be an early marker of smoking-related lung disease in young
      adults, instead of a marker of reversible obstructive lung disease, which may
      have important implications for the approach to young people presenting with
      respiratory symptoms suggesting asthma.

PMID- 16291079
TI  - Lung function in type 2 diabetes: the Normative Aging Study.
AB  - BACKGROUND: Cross-sectional studies have noted that subjects with diabetes have
      lower lung function than non-diabetic subjects. We conducted this analysis to
      determine whether diabetic subjects have different rates of lung function change
      compared with non-diabetic subjects. METHODS: We conducted a nested case-control
      analysis in 352 men who developed diabetes and 352 non-diabetic subjects in a
      longitudinal observational study of aging in men. We assessed lung function among
      cases and controls at three time points: Time0, prior to meeting the definition
      of diabetes; Time1, the point when the definition of diabetes was met; and Time2,
      the most recent follow-up exam. RESULTS: Cases had lower forced expiratory volume
      in 1s (FEV1) and forced vital capacity (FVC) at all time points, even with
      adjustment for age, height, weight, and smoking. In multiple linear regression
      models adjusting for relevant covariates, there were no differences in rates of
      FEV1 or FVC change over time between cases and controls. CONCLUSIONS: Men who are
      predisposed to develop diabetes have decreased lung function many years prior to
      the diagnosis, compared with men who do not develop diabetes. This decrement in
      lung function remains after the development of diabetes. We postulate that
      mechanisms involved in the insulin resistant state contribute to the diminished
      lung function observed in our subjects.

PMID- 16291080
TI  - Discrepant nasal and bronchial nitric oxide kinetics during early and late phase
      allergic reactions.
AB  - Late allergic reactions (LAR) following allergen challenge occur in different
      compartments. We studied the kinetics of nasal and bronchial nitric oxide (NO) in
      mild asthmatics after allergen challenge. Twelve males with intermittent asthma
      (28 yr, FEV1 97% of predicted, PC20methacholine <8 mg/ml) and known LAR after
      bronchial allergen challenge underwent nasal and bronchial allergen provocation
      using the same allergen separated by a washout of 3 weeks. Nasal and bronchial NO
      were measured before challenge, during early (EAR) and late phase reactions, and
      24 h after allergen. The mean (sem) maximum fall of FEV1 at EAR was 31.9+/-3.2%
      (P=0.001), and 17.6+/-2.2% (P=0.004) during LAR. All patients developed nasal EAR
      (max. fall in nasal rhinomanometric flow 64.8+/-7.6% of baseline) after nasal
      challenge, and 10 patients demonstrated nasal LAR with a fall in nasal flow of
      65.9+/-6.6% (both P=0.002, respectively). During EAR, there was stronger
      reduction of nasal (-19.2+/-6.2%,P=0.039) than bronchial NO (-6.9+/-5.2% of
      baseline, P=ns). In contrast, bronchial NO also tended to decrease during
      bronchial LAR (-8.8+/-6.8%,P=ns), while nasal NO slightly increased non
      significantly (+17+/-10.8%, P=ns). After 24 h, bronchial NO was significantly
      elevated (+78.1+/-40.1%, P=0.039), whereas nasal NO was unchanged (+6.1+/-15.1%,
      P=ns). The intraindividual difference between bronchial and nasal changes of NO
      during LAR, but not EAR or after 24 h, was significant (lung vs. nose: -35.6+/
      14.1% relative difference, P=0.039). Despite similar functional responses in nose
      and bronchi, nasal NO kinetics following allergen challenge differ from bronchial
      NO. The concise mechanisms accounting for this discrepancy warrant further
      investigations.

PMID- 16291081
TI  - Christmas surprise: the unnoticed journey of a needle-from bronchus to intestine.
AB  - We report on a 14-year-old Arabian girl who suddenly developed coughing after
      having aspirated a needle used for fixing her headscarf. The chest X-ray showed
      the needle located in the right main bronchus. However, subsequent flexible
      bronchoscopy could not detect any foreign body. A further X-ray of the abdomen
      showed the needle now behind the diaphragm. Gastro-oesophageal endoscopy was also
      uneventful. On the third day, the needle was excreted naturally. Astonishingly,
      this journey of the wandering needle from bronchus to intestine was not realised
      by the patient at any time. Our case highlights that children and adolescents
      should be warned repeatedly about the risks of putting needles between their
      teeth. It also reminds the physician to diagnose aspirated foreign bodies as
      early as possible to prevent wandering and migrating, which may induce new risks
      and unnecessary diagnostic and therapeutic procedures.

PMID- 16291082
TI  - Pleurovenous shunt in treating refractory nonmalignant hepatic hydrothorax: a
      case report.
AB  - We report a case of successful, long-term pleurovenous shunt (PVS) in treating
      refractory nonmalignant hepatic hydrothorax. An 82-year-old woman with liver
      cirrhosis, hypertension complicated with chronic renal failure while on
      hemodialysis, presented with progressive dyspnea in association with a recurrent
      right-sided pleural effusion, occurring secondary to transdiaphragmatic migration
      of ascites. The diagnosis was established by a demonstration of (99m)Tc-sulphur
      colloid sequential scintigraphic scan. Despite repetitive thoracenteses and
      traditional medical treatment, she suffered dyspnea without relief. Denver
      peritoneovenous shunt was inserted into the right-sided pleural cavity to drain
      effusion into the subclavian vein without short- and long-term complications.
      Manually pumping schedule of 10 min was performed twice daily to remove pleural
      fluid into the venous circulation for maintaining shunt patency. After 19 months
      of follow-up, the patient is doing well and PVS remains patent without
      significant pleural effusion. PVS opens a window of opportunity and offers an
      alternative procedure with minimal invasiveness for high-risk patients with
      refractory hepatic hydrothorax. It could be an alternative treatment to other
      conventional surgical interventions.

PMID- 16291083
TI  - Early bronchial airflow impairment in patients with persistent allergic rhinitis
      and bronchial hyperreactivity.
AB  - BACKGROUND: Allergic rhinitis and its impact on asthma (ARIA) document underlines
      the link between upper and lower airways. Patients suffering from allergic
      rhinitis frequently (up to 80%) show bronchial hyperreactivity (BHR). OBJECTIVES:
      This study aimed at evaluating a group of subjects suffering from persistent
      allergic rhinitis, with BHR but with nasal symptoms only, to investigate the type
      and intensity of nasal symptoms, nasal and bronchial airflow, and BHR grade
      during the pollen season. METHODS: One hundred and twenty one polysensitized
      rhinitics were investigated. Total symptom score (TSS) was assessed in all
      patients. Rhinomanometry, spirometry and methacholine bronchial challenge were
      performed in all patients. RESULTS: 65 (53.7%) patients had impaired FEF 25-75
      values. TSS correlated with nasal airflow (P<0.001) and BHR grade (P<0.001).
      Nasal airflow correlated with FEF 25-75 values (P<0.05) and BHR (P<0.001). FEF 25
      75 values correlated with FEV(1) levels (P<0.003), BHR grade (P<0.001), and nasal
      obstruction symptom (P<0.05). Severe BHR correlated with FEV(1) (P<0.05) and FEF
      25-75 (P<0.03) values, nasal airflow (P<0.05) and nasal symptoms (P<0.001).
      CONCLUSIONS: This study evidences that early bronchial impairment is frequently
      detectable in patients with persistent allergic rhinitis and BHR. Moreover, nasal
      function is strictly related with bronchial calibre and BHR grade. Therefore,
      careful evaluation of lower airways should be investigated in all rhinitics as
      suggested by the ARIA document.

PMID- 16291084
TI  - Response: Utilization of FEV6 in place of FVC may lead to underestimation of mild
      airway obstruction.

PMID- 16291085
TI  - Multi-centre pilot study of 2-chlorodeoxyadenosine and cytosine arabinoside
      combined chemotherapy in refractory Langerhans cell histiocytosis with
      haematological dysfunction.
AB  - The aim of this study was to assess the efficacy and adverse effects of 2
      chlorodeoxyadenosine (2-CdA) and cytosine arabinoside (Ara-C) in children with
      refractory Langerhans cell histiocytosis (LCH) and haematopoietic dysfunction.
      Ten patients, with a median age at diagnosis of 0.5 years, were enrolled in this
      study. Treatment comprised at least two courses of Ara-C (1000 mg/m(2)/d) and 2
      CdA (9 mg/m(2)/d) administered for 5d every 4 weeks; subsequent median follow-up
      was 2.8 years (range 0.03-6.4 years). Among the 7 patients who received at least
      two courses of therapy, disease activity decreased in 6 patients, and control of
      disease was achieved in all patients after a median delay of 5.5 months. All
      patients suffered World Health Organisation (WHO) grade 4 haematological
      toxicity. Two septic deaths occurred shortly after administration of the first
      course of 2-CdA/Ara-C; a third patient was withdrawn from the trial after the
      first course and subsequently died following haematopoietic stem cell
      transplantation. This series is small, but we conclude that 2-CdA and Ara-C
      combined chemotherapy probably has major activity in childhood refractory
      Langerhans cell histiocytosis.

PMID- 16291086
TI  - Inhibition of human androgen-independent PC-3 and DU-145 prostate cancers by
      antagonists of bombesin and growth hormone releasing hormone is linked to PKC,
      MAPK and c-jun intracellular signalling.
AB  - Bombesin/gastrin-releasing peptide (BN/GRP) antagonists RC-3940-II and RC-3940
      Et, and growth hormone-releasing hormone (GHRH) antagonists MZ-J-7-118 and RC-J
      29-18 inhibit the growth of human androgen-independent PC-3 and DU-145 prostate
      cancers in nude mice. Additive inhibitory effects were observed after treatment
      with both classes of analogs. In the present study, we investigated the effects
      of these antagonists on intracellular signalling pathways of protein kinase C
      (PKC), mitogen activated protein kinases (MAPK) and c-fos and c-jun oncogenes
      that are involved in tumour cell proliferation. In PC-3 tumours, antagonists of
      BN/GRP and GHRH decreased significantly the expression of PKC isoforms alpha
      (alpha), eta (eta) and zeta (zeta) and increased that of delta (delta) PKC
      protein. MAPK was not detectable. In DU-145 tumours, which constitutively express
      MAPK, all treatments strongly decreased the levels of p42/44 MAPK. Treatment with
      the antagonists tended to reduce m-RNA for c-jun in both tumour models. In
      proliferation assays in vitro, inhibitors of PKC and MAPK diminished growth of DU
      145 and PC-3 cells. These findings suggest that antagonists of BN/GRP and GHRH
      inhibit the growth of androgen-independent prostate cancer by affecting
      intracellular signalling mechanisms of PKC, MAPK and c-jun.

PMID- 16291087
TI  - Crystal structure at 1.1 Angstroms resolution of an insect myrosinase from
      Brevicoryne brassicae shows its close relationship to beta-glucosidases.
AB  - The aphid Brevicoryne brassicae is a specialist feeding on Brassicaceae plants.
      The insect has an intricate defence system involving a beta-D-thioglucosidase
      (myrosinase) that hydrolyses glucosinolates sequestered from the host plant into
      volatile isothiocyanates. These isothiocyanates act synergistically with the
      pheromone E-beta-farnesene to form an alarm system when the aphid is predated. In
      order to investigate the enzymatic characteristics of the aphid myrosinase and
      its three-dimensional structure, milligram amounts of pure recombinant aphid
      myrosinase were obtained from Echerichia coli. The recombinant enzyme had similar
      physiochemical properties to the native enzyme. The global structure is very
      similar to Sinapis alba myrosinase and plant beta-O-glucosidases. Aphid
      myrosinase has two catalytic glutamic acid residues positioned as in plant beta-O
      glucosidases, and it is not obvious why this unusual enzyme hydrolyses
      glucosinolates, the common substrates of plant myrosinases which are normally not
      hydrolyzed by plant beta-O-glucosidases. The only residue specific for aphid
      myrosinase in proximity of the glycosidic linkage is Tyr180 which may have a
      catalytic role. The aglycon binding site differs strongly from plant myrosinase,
      whereas due to the presence of Trp424 in the glucose binding site, this part of
      the active site is more similar to plant beta-O-glucosidases, as plant
      myrosinases carry a phenylalanine residue at this position.

PMID- 16291088
TI  - A cell-free mRNA stability assay reveals conservation of the enzymes and
      mechanisms of mRNA decay between mosquito and mammalian cell lines.
AB  - The rate of mRNA turnover is an important determinant of levels of gene
      expression. Although this process has been studied extensively in mammalian cells
      and yeast, relatively little is known about the mRNA decay pathways in insects.
      Our analysis found that the vast majority of components of the mRNA decay
      machinery are conserved between humans and mosquitoes. Moreover, the half-lives
      of Aedes albopictus mRNAs are within a similar range to those of mammalian mRNAs.
      In order to investigate mechanistic aspects of mRNA decay in mosquitoes, we
      developed an in vitro system using cytoplasmic S100 extracts from A. albopictus
      C6/36 cells. Using this decay assay, we show here that all the pathways of mRNA
      turnover that have been observed in mammalian cells (deadenylation, decapping, 3'
      to-5' exonucleolytic decay and 5'-to-3' exonucleolytic decay) are active in C6/36
      extracts. Finally, we present compelling evidence that the major deadenylase in
      C6/36 extracts is likely to be a homolog of the human poly(A) specific
      ribonuclease, PARN. Our results suggest a high level of conservation in the
      factors and pathways of mRNA decay between mosquitoes and humans.

PMID- 16291089
TI  - Immune challenge differentially affects transcript abundance of three
      antimicrobial peptides in hemocytes from the moth Pseudoplusia includens.
AB  - Inducible expression of antimicrobial peptides and other humoral immune factors
      by the insect fat body is well documented. Hemocytes comprise the second
      essential arm of the insect immune system but it is unclear whether antimicrobial
      peptide genes are expressed by all or only some types of hemocytes. Here we
      report the cloning of cecropin A (Pi-cecA), lebocin (Pi-leb) and lysozyme (Pi
      lys) homologs from the moth Pseudoplusia includens. Relative-quantitative real
      time PCR (rq-rtPCR) indicated that transcript abundance for each antimicrobial
      gene increased in fat body and hemocytes following immune challenge with the Gram
      negative bacterium Escherichia coli. Relative transcript abundance of Pi-cecA was
      much higher in fat body than hemocytes. In contrast, transcript levels of Pi-leb
      were three-fold lower in hemocytes than fat body while transcript levels of Pi
      lys were three-fold higher. Estimates for the overall contribution of the fat
      body and hemocytes to antimicrobial peptide expression suggested that hemocytes
      contribute significantly to Pi-lys transcript levels in larvae but produce much
      smaller amounts of Pi-cecA and Pi-leb compared to the fat body. Each
      antimicrobial peptide was also inducibly expressed in hemocytes following
      challenge with the Gram-positive bacterium Micrococcus luteus or when hemocytes
      formed capsules around chromatography beads. Analysis of hemocyte types indicated
      that granulocytes and plasmatocytes expressed all three antimicrobial peptides,
      whereas spherule cells and oenocytoids expressed only lysozyme. Transcriptional
      profiles of these antimicrobial genes were similar in granulocytes and
      plasmatocytes in vivo but were very different in vitro.

PMID- 16291090
TI  - Pharmacological profiles of recombinant and native insect nicotinic acetylcholine
      receptors.
AB  - Nicotinic acetylcholine receptors (nAChRs) are targets for insect-selective
      neonicotinoid insecticides exemplified by imidacloprid (IMI) and mammalian
      selective nicotinoids including nicotine and epibatidine (EPI). Despite their
      importance, insect nAChRs are poorly understood compared with their vertebrate
      counterparts. This study characterizes the [(3)H]IMI, [(3)H]EPI, and [(3)H]alpha
      bungarotoxin (alpha-BGT) binding sites in hybrid nAChRs consisting of Drosophila
      melanogaster (fruit fly) or Myzus persicae (peach-potato aphid) alpha2
      coassembled with rat beta2 subunits (Dalpha2/Rbeta2 and Mpalpha2/Rbeta2) and
      compares them with native insect and vertebrate alpha4beta2nAChRs. [(3)H]IMI and
      [(3)H]EPI bind to Dalpha2/Rbeta2 and Mpalpha2/Rbeta2 hybrids but [(3)H]alpha-BGT
      does not. In native Drosophila receptors, [(3)H]EPI has a single high-affinity
      binding site that is independent from that for [(3)H]IMI and, interestingly,
      overlaps the [(3)H]alpha-BGT site. In the Mpalpha2/Rbeta2 hybrid, [(3)H]IMI and
      [(3)H]EPI bind to the same site and have similar pharmacological profiles. On
      considering both neonicotinoids and nicotinoids, the Dalpha2/Rbeta2 and
      Mpalpha2/Rbeta2 receptors display intermediate pharmacological profiles between
      those of native insect and vertebrate alpha4beta2 receptors, limiting the use of
      these hybrid receptors for predictive toxicology. These findings are consistent
      with the agonist binding site being located at the nAChR subunit interface and
      indicate that both alpha and beta subunits influence the pharmacological
      properties of insect nAChRs.

PMID- 16291091
TI  - Prophenoloxidase binds to the surface of hemocytes and is involved in hemocyte
      melanization in Manduca sexta.
AB  - In insects, melanotic encapsulation is an important innate immune response
      against large pathogens or parasites, and phenoloxidase (PO) is a key enzyme in
      this process. Activation of prophenoloxidase (proPO) to PO is mediated by a
      serine proteinase cascade. PO has a tendency to adhere to foreign surfaces
      including hemocyte surfaces. In this study, we showed that in the naive larvae of
      the tobacco hornworm Manduca sexta, hemolymph proPO bound to the surface of
      granulocytes and spherule cells but not to oenocytoids, and about 10% hemocytes
      had proPO on their surfaces. When larvae were injected with water (injury) or
      microsphere beads (immune-challenge), hemolymph proPO was activated, and the
      number of hemocytes with surface proPO/PO increased at 12 h post-injection, but
      dropped to the normal level at 24 h. Hemocyte surface proPO can be activated in
      vitro, leading to melanization of these hemocytes. The number of melanized
      hemocytes from the larvae injected with water or microsphere beads significantly
      increased. We also showed that neither hemocytes nor cell-free plasma alone
      triggered melanization of immulectin-2-coated agarose beads in vitro. However,
      agarose beads were effectively melanized by isolated hemocytes in the presence of
      cell-free plasma. Our results suggest that activation of hemocyte surface proPO
      may initiate melanization, leading to the systemic melanization of hemocyte
      capsules.

PMID- 16291092
TI  - Pteropsin: a vertebrate-like non-visual opsin expressed in the honey bee brain.
AB  - Insects have excellent color vision based on the expression of different opsins
      in specific sets of photoreceptive cells. Opsins are members of the rhodopsin
      superfamily of G-protein coupled receptors, and are transmembrane proteins found
      coupled to light-sensitive chromophores in animal photoreceptors. Diversification
      of opsins during animal evolution provided the basis for the development of
      wavelength-specific behavior and color vision, but with the exception of the
      recently discovered non-visual melanopsins, vertebrate and invertebrate opsins
      have generally been viewed as representing distinct lineages. We report a novel
      lineage of insect opsins, designated pteropsins. On the basis of sequence
      analysis and intron location, pteropsins are more closely related to vertebrate
      visual opsins than to invertebrate opsins. Of note is that the pteropsins are
      missing entirely from the genome of drosophilid flies. In situ hybridization
      studies of the honey bee, Apis mellifera, revealed that pteropsin is expressed in
      the brain of this species and not in either the simple or compound eyes. It was
      also possible, on the basis of in situ hybridization studies, to assign different
      long wavelength opsins to the compound eyes (AmLop1) and ocelli (AmLop2). Insect
      pteropsin might be orthologous to a ciliary opsin recently described from the
      annelid Platynereis, and therefore represents the presence of this vertebrate
      like light-detecting system in insects.

PMID- 16291093
TI  - Molecular cloning of a phospholipid-hydroperoxide glutathione peroxidase gene
      from the tick, Boophilus microplus (Acari: Ixodidae).
AB  - Phospholipid-hydroperoxide glutathione peroxidase (PHGPx) enzymes are associated
      with cellular protection by the role they play in reducing hydroperoxides of
      phospholipids, thereby preventing membrane lipoperoxidation. As part of their
      toxic effect, some pesticides stimulate peroxidation of cellular membranes. We
      isolated and sequenced a PHGPx gene from the cattle tick Boophilus microplus that
      encodes a protein of 169 amino acids, including a TGA-encoded selenocysteine at
      residue 46 and active site residues Gln(82) and Trp(135) that interact with the
      selenocysteine. The motif that directs the insertion of selenocysteine at the
      opal codon is found in the 3'-untranslated region. PHGPx sequences from pesticide
      resistant and susceptible B. microplus ticks show nucleotide differences at eight
      positions among the strains, with five resulting in amino acid substitutions in
      the deduced protein sequence. Two distinct PHGPx alleles were identified in an
      organophosphate-resistant tick strain. Real-time PCR quantification of gene
      expression revealed increased PHGPx in two strains resistant to a single
      acaricide class. Strains resistant to two or more classes showed a reduction in
      PHGPx.

PMID- 16291094
TI  - Molecular phylogenetics of monarch flycatchers (genus Monarcha) with emphasis on
      Solomon Island endemics.
AB  - Systematic relationships among monarch flycatchers (genus Monarcha) are poorly
      understood despite dramatic patterns of morphological differentiation that have
      long attracted the attention of evolutionary biologists. With sequence data from
      the mitochondrial ND2 gene and Control Region, we produced a phylogenetic
      hypothesis for evolutionary relationships within Monarcha and among the
      biogeographically complex Solomon Island endemics. Outgroup analyses contradicted
      monophyly of the genus by imbedding a representative of the genus Clytorhynchus
      within one of two major clades recovered within Monarcha. These two monarch
      clades generally correspond with ecological and morphological distinctions,
      suggesting the genus may warrant revision pending the inclusion of taxa currently
      allied with Clytorhynchus (e.g., Neolalage spp.). Maximum likelihood
      reconstructions support monophyletic groupings of the two endemic Solomon Island
      monarch radiations, however, two currently recognized superspecies (Monarcha
      manadensis and M. melanopsis) were polyphyletic and paraphyletic, respectively.
      Interestingly, molecular and morphological differentiation were strikingly
      decoupled among several Solomon Island endemics and between migratory and non
      migratory forms of Monarcha trivirgatus in eastern Australia, suggesting
      morphological evolution has masked the true history of speciation in these
      groups. This initial phylogeny provides a novel platform for ongoing exploration
      of the history underlying dramatic patterns of geographic variation among
      tropical Pacific flycatchers.

PMID- 16291095
TI  - A call for likelihood phylogenetics even when the process of sequence evolution
      is heterogeneous.

PMID- 16291096
TI  - The surgical treatment of disc degeneration: is the race not to the swift?

PMID- 16291097
TI  - Response of Charite total disc replacement under physiologic loads: prosthesis
      component motion patterns.
AB  - BACKGROUND CONTEXT: Total disc replacement (TDR) has been recommended to reduce
      pain of presumed discogenic origin while preserving spinal motion. The floating
      core of Charite TDR is professed to allow the replication of the kinematics of a
      healthy disc under physiologic loads. While segmental motion after Charite TDR
      has been measured, little is known about the effects of a physiologic compressive
      preload on vertebral motion and the motion of prosthesis components after TDR.
      PURPOSE: (1) Does Charite TDR allow restoration of normal load-displacement
      behavior of a lumbar motion segment under physiologic loads? (2) How do the
      prosthesis components move relative to each other under physiologic loads when
      implanted in a lumbar motion segment? STUDY DESIGN: A biomechanical study using
      human lumbar spines (L1-sacrum). METHODS: Five lumbar spines (age: 52+/-9.3) were
      used. Specimens were tested under flexion (8 Nm) and extension (6 Nm) moments
      with compressive follower preloads of 0 N and 400 N in the following sequence:
      (i) intact, (ii) Charite TDR at L5-S1, (iii) simulated healed fusion at L5-S1
      with Charite TDR at L4-L5. Segmental motion was measured optoelectronically.
      Motions between prosthesis end plates and core were visually assessed using
      sequential digital video-fluoroscopy over the full range of motion. Here we
      report on kinematics of 10 Charite TDRs: 5 at L5-S1 and 5 at L4-L5. RESULTS:
      Charite TDR increased the flexion-extension range of motion of lumbar segments
      (p<.05). At 400 N preload, the range of motion increased from intact values of
      6.8+/-4.4 to 10.0+/-2.4 degrees at L5-S1 and from 7.0+/-2.6 to 10.8+/-2.9 degrees
      at L4-L5. Charite TDR increased segmental lordosis by 8.1+/-6.9 degrees at L5-S1
      (p<.05) and 5.4+/-3.5 degrees at L4-L5 (p<.05). Four patterns of prosthesis
      component motion were noted: (1) angular motion only between the upper end plate
      and core, with little or no visual evidence of core translation (9 of 10 TDRs at
      0 N preload and 5 of 10 TDRs at 400 N preload); (2) lift-off of upper prosthesis
      end plate from core or of core from lower end plate (observed in extension in 9
      of 10 TDRs under 0 N preload only); (3) core entrapment, resulting in a locked
      core over a portion of the range of motion (observed in extension in 8 of 10 TDRs
      under 400 N preload); (4) angular motion between both the upper and lower end
      plates and core, with visual evidence of core translation (1 of 10 TDRs at 0 N
      preload, 5 of 10 TDRs at 400 N preload). The pattern of load-displacement curves
      was substantially changed under a physiologic preload in 8 of 10 TDRs; instead of
      a relatively gradual change in angle with changing moment application as seen for
      an intact segment, the TDR displayed regions of both relatively small and
      relatively large angular changes with gradual moment application. CONCLUSIONS:
      Charite TDR restored near normal quantity of flexion-extension range of motion
      under a constant physiologic preload; however, the quality of segmental motion
      differed from the intact case over the flexion-extension range. Whereas some TDRs
      showed visual evidence of core translation, the predominant angular motion within
      the prosthesis occurred between the upper end plate and the polyethylene core.
      Likely factors affecting the function of the Charite TDR include implant
      placement and orientation, intraoperative change in lordosis, and magnitude of
      physiologic compressive preload. Further work is needed to assess the effects of
      the prosthesis motion patterns identified in the study on the load sharing at the
      implanted level and polyethylene core wear.

PMID- 16291098
TI  - Two-level posterior lumbar interbody fusion for degenerative disc disease:
      improved clinical outcome with restoration of lumbar lordosis.
AB  - BACKGROUND CONTEXT: Although posterior lumbar interbody fusion (PLIF) for
      degenerative lumbar diseases is routine, there are few reports on double-level
      PLIF. PURPOSE: To evaluate the clinical outcomes of double-level PLIF. STUDY
      DESIGN/SETTING: A retrospective study of operated cases in Gifu, Japan. PATIENT
      SAMPLE: Nineteen patients (8 men and 11 women, 59.5+/-10.2 years) who underwent
      double-level PLIF between 1996 and 2001. OUTCOME MEASURES: Operation time, blood
      loss, complications, the Japanese Orthopaedic Association (JOA) score for back
      pain and lumbar sagittal alignment were evaluated. METHODS: Patients were
      examined retrospectively at follow-ups of 3.6+/-1.7 years. Primary diseases were
      spondylolisthesis, spinal canal stenosis, degenerative scoliosis and herniated
      intervertebral disc. Fusion areas were L3 to L5 in 15 cases and L4 to S1 in 4
      cases. RESULTS: The mean JOA score increased from an initial score of 12.9+/-3.5
      to 21.3+/-4.9 at the final follow-up. There was a positive correlation (R=0.718,
      p<.001) between the increase in lordotic angle and the increase in the JOA score.
      Several parameters suggested that the surgical invasiveness was not minimal.
      CONCLUSION: Double-level PLIF provided satisfactory results and preserved lumbar
      spine lordosis.

PMID- 16291099
TI  - Percent spinal canal compromise on MRI utilized for predicting the need for
      surgical treatment in single-level lumbar intervertebral disc herniation.
AB  - BACKGROUND CONTEXT: There is limited information describing the correlation
      between the initial quantitative measurements on magnetic resonance imaging (MRI)
      scans of disc herniation area, canal cross-section areas, percent canal
      compromise, and disc herniation location to the need for surgery. PURPOSE: Our
      aim is to determine if the size of disc herniation area, canal cross-section
      area, percent canal compromise, and disc herniation location taken from MRI
      images of patients with symptomatic single-level lumbar herniated intervertebral
      discs upon initial presentation to a spine surgeon, were predictive of the need
      for surgical treatment. STUDY DESIGN/SETTING: This is a retrospective case
      matched study of patient MRI images in the senior author's private practice.
      PATIENT SAMPLE: From a pool of 332 patients with sciatica caused by lumbar
      intervertebral disc herniations at our institution, 65 patients had surgery, of
      which MRI images were available and analyzed on 44 patients. Forty-four
      additional patients were randomly selected from the remaining 267 original group
      as nonoperative controls. METHODS: The axial MRI image showing the largest canal
      compromise by the herniated disc was selected for measurements. Using T1- and T2
      weighted images, the areas of interest were digitally scanned at high resolution.
      The canal area and disc herniation area measurement were calculated from the
      total number of pixels per cross-sectional area, multiplied by a scan correction
      factor, mm(2) /pixel. Disc herniation locations were classified into either
      central or paracentral. The percent canal compromise was obtained by disc
      herniation area divided by canal cross-section area and multiplied by 100.
      RESULTS: The surgical group's overall mean herniated disc area was 219.6 square
      millimeter (mm(2)), 179.8 at L4-5, and 267.4 at L5-S1. The nonoperative group's
      overall mean herniated disc area was 178.4 mm(2), 135.1 at L2-3, 160.3 at L4-5,
      and 207.4 at L5-S1. The surgical group's overall mean canal cross-sectional area
      was 471.8 mm(2), 418.6 at L4-5, and 535.6 at L5-S1. The nonoperative group's
      overall mean canal cross-sectional area was 541.3 mm(2), 518.1 at L2-3, 446.8 at
      L4-5, and 669.9 at L5-S1. The overall percent canal compromise ratio in the
      surgery group was 46.7%, 44.1% at L4-5, and 49.8% at L5-S1. The overall percent
      canal compromise in the nonoperative group was 34.2%, 34.1% at L2-3, 36.1% at L4
      5, and 31.8% at L5-S1. The percent canal compromise in central herniations at L4
      5 level was 53.0% in the surgical group, and 32.8% in the nonoperative group; at
      the L5-S1 level surgical group percent canal compromise was 64.1% and in the
      nonoperative group canal compromise was 27%. L4-L5 level paracentral herniations
      canal compromise was 36.7% in the surgical group compared with 42.5% canal
      compromise in the nonoperative group. At the L5-S1 level the canal compromise was
      45% in the surgical group and 34.8% in the nonoperative group. CONCLUSIONS: Our
      findings show a trend for patients treated with surgery to have larger disc
      herniation areas and smaller canal cross-section areas, corresponding to larger
      percent canal compromise than the nonoperative group. Centrally located
      herniations followed this trend closely at all levels studied. However, the
      paracentral herniation at the L4-5 level does not follow this trend, possibly
      because paracentral disc herniation clinical course is determined more by
      herniation location rather than the overall herniation size.

PMID- 16291100
TI  - Congenital lumbar spinal stenosis: a prospective, control-matched, cohort
      radiographic analysis.
AB  - BACKGROUND CONTEXT: Degenerative lumbar spinal stenosis manifests primarily after
      the sixth decade of life as a result of facet hypertrophy and degenerative disc
      disease. Congenital stenosis, on the other hand, presents earlier in age with
      similar clinical findings but with multilevel involvement and fewer degenerative
      changes. These patients may have subtle anatomic variations of the lumbar spine
      that may increase the likelihood of thecal sac compression. However, to the
      authors' knowledge, no quantitative studies have addressed various radiographic
      parameters of symptomatic, congenitally stenotic individuals to normal subjects.
      PURPOSE: To radiographically quantify and compare the anatomy of the lumbar spine
      in symptomatic, congenitally stenotic individuals to age- and sex-matched,
      asymptomatic, nonstenotic controlled individuals. STUDY DESIGN/SETTING: A
      prospective, control-matched, cohort radiographic analysis. PATIENT SAMPLE: Axial
      and sagittal magnetic resonance imaging (MRI) and lateral, lumbar, plain
      radiographs of 20 surgically treated patients who were given a clinical diagnosis
      of congenital lumbar stenosis by the senior author were randomized with images of
      20, asymptomatic age- and sex-matched subjects. OUTCOME MEASURES: MRIs and
      lateral, lumbar, plain radiographs were independently quantitatively assessed by
      two individuals. Measurements obtained from the axial MRIs included: midline
      anterior-posterior (AP) vertebral body diameter, vertebral body width, midline AP
      canal diameter, canal width, spinal canal cross-sectional area, pedicle length,
      and pedicle width. From the sagittal MRIs, the following measurements were
      calculated: AP vertebral body diameter, vertebral body height, and AP canal
      diameter at the mid-vertebral level. On the lateral, lumbar, plain radiograph (L3
      level), the AP diameters of the vertebral body spinal canal were measured.
      METHODS: The images of these 40 individuals were then randomized and distributed
      in a blinded fashion to five separate spine surgeons who graded the presence and
      severity of congenital stenosis utilizing a five-tier scale. Images consisting of
      15 symptomatic individuals, graded definitely congenitally stenotic (mean age,
      51.7 years; range, 43-65 years), and 15 asymptomatic individuals, graded
      definitely not stenotic (mean age, 50.7 years; range, 41-55 years), were age- and
      sex-matched and included for further review. From these 30 patients, a lateral,
      lumbar, plain radiograph and axial and sagittal MRIs (T1/T2 weighted) from L2-L5
      were quantitatively analyzed. Rater reliability was assessed by Kappa coefficient
      testing. RESULTS: The cross-sectional area of the canal was significantly smaller
      in the congenitally stenotic patients at all lumbar levels measured (L2: 176
      mm(2) vs. 259 mm(2), L3: 177 mm(2) vs. 275 mm(2), L4: 183 mm(2) vs. 283 mm(2),
      L5: 213 mm(2) vs. 323 mm(2), p<.05). Pedicle length was markedly shorter in the
      stenosis group at each lumbar level (L2: 5.9 mm vs. 8.9 mm, L3: 6.0 mm vs. 8.8
      mm, L4: 6.5 mm vs. 9.2 mm, L5: 5.8 mm vs. 9.1 mm, p<.05). Furthermore, midline,
      axial AP canal diameter, vertebral body width, and sagittal AP canal diameter
      were all significantly smaller than the control patients (p<.05). A ratio of the
      AP diameter of the pedicle length to the vertebral body was also noted to be
      statistically significant on both the lateral plain radiographs (L3: 0.426 vs.
      0.704) and sagittal MRI (L2: 0.343 vs. 0.461, L3: 0.361 vs. 0.461, L4: 0.362 vs.
      0.481, L5: 0.354 vs. 0.452, p<.05). No difference was noted comparing the AP
      diameter of the vertebral body (axial and sagittal images), vertebral body
      height, canal width, and pedicle width. Kappa testing coefficient indicated a
      strong rater reliability (k=0.81, 95% confidence interval: 0.62-0.94).
      CONCLUSIONS: Congenital lumbar stenosis has not been clearly defined
      radiographically. Clinically, congenitally stenotic patients present at a younger
      age with fewer degenerative changes and multiple levels of involvement.
      Radiographically, these patients have a shorter pedicular length and as a result
      a smaller cross-sectional spinal canal area (mean critical values of 6.5 mm and
      213 mm(2) were observed, respectively). The mean critical ratios were 0.43 (2:1
      AP vertebral body: pedicle length) on the lateral lumbar radiograph and 0.36 on
      the sagittal MRI. The altered canal anatomy resulting from a decreased pedicle
      length may anatomically predispose these patients to earlier complaints of
      symptomatic neurogenic claudication. Identification of the presence of congenital
      stenosis should increase the treating surgeon's awareness of the potential need
      for multilevel treatment.

PMID- 16291101
TI  - Variation in the human cervical neural canal.
AB  - BACKGROUND CONTEXT: The dimensions of the cervical spinal canal can impact the
      likelihood of an individual suffering longtime effects from a spinal neck injury
      as well as influence recovery time. Most studies have used radiographic studies
      to compare differences in the neural canal, but few have examined skeletal
      populations to determine variation in the neural canal dimensions without the
      presence of soft tissue. PURPOSE: To analyze variation seen in the cervical
      neural canal (anterior-posterior and transverse diameters) with respect to sex
      and ancestry and to define cervical canal narrowing in the sample. STUDY DESIGN:
      Observational. METHODS: Measurements of the anterior-posterior (sagittal) (CAP)
      and transverse (CTR) diameters were taken from 321 individual skeletons.
      Comparisons were made between males and females and individuals belonging to
      different ancestral (racial) groups. RESULTS: CAP was narrowest at the C4 level
      for African-Americans and at C6 for Caucasians. CTR was narrowest at the C2/C3
      level for all groups. Statistical analyses indicated that significant differences
      in cervical canal dimensions are due first to sexual dimorphism and then to
      ancestry. CONCLUSIONS: Significant variation in cervical canal dimensions
      precludes usage of universal definitions to determine spinal stenosis in
      individuals; definitions should be according to sex and ancestry.

PMID- 16291102
TI  - Mini-open thoracoscopically assisted thoracotomy versus video-assisted
      thoracoscopic surgery for anterior release in thoracic scoliosis and kyphosis: a
      comparison of operative and radiographic results.
AB  - BACKGROUND CONTEXT: Combining anterior release and interbody fusion with
      posterior instrumented fusion is an accepted treatment for severe rigid spinal
      deformity. Video-assisted thoracoscopic surgery (VATS) and mini-open
      thoracoscopically assisted thoracotomy (MOTA) are two minimally invasive
      approaches to the thoracic spine. Both reduce surgical trauma, improve cosmesis
      and provide effective exposure for release and fusion. Published data and the
      authors' surgical experience have demonstrated that both techniques are
      equivalent in degree of release to traditional open thoracotomy, but no
      comparison between these two minimally invasive alternatives has been published
      to our knowledge. PURPOSE: This study compared MOTA and VATS under the hypothesis
      that both result in similar corrections and comparable operative parameters when
      used in conjunction with posterior instrumented fusion. STUDY DESIGN/SETTING:
      Retrospective chart review of consecutive case series by two surgeons. PATIENT
      SAMPLE: Twenty-one (13 female, 8 male) patients underwent MOTA and 24 patients
      (17 female, 7 male) underwent VATS for anterior release, discectomy and fusion
      prior to posterior instrumented fusion. OUTCOME MEASURES: Outcomes were measured
      at a minimum of 1-year follow-up and included radiographic Cobb measurements and
      operative parameters. METHODS: The indications for surgery included rigid and
      severe scoliosis or thoracic kyphosis. Data collection included preoperative
      demographics, number of levels released, primary curve correction, operative time
      and blood loss. Data were normalized per number of levels released anteriorly.
      Statistical analysis of results was done using a two-sample t test assuming equal
      variances with two-tail p values less than .05. RESULTS: More anterior levels
      were operated on average in the VATS group (6.33 vs. 4.38 levels). Curve
      correction per anterior level released was similar in both groups (8.7 and 8.8
      degrees/level for MOTA and VATS, respectively). There was a significant
      difference in operative time with MOTA averaging 131.7 minutes and VATS averaging
      162.8 minutes. However, a comparison of the operative time per anterior level
      operated, approached statistical significance in favor of VATS (33.0 vs. 28.4
      minutes, p=.08). There was no significant difference in estimated blood loss
      during the anterior portion of the surgeries. There was a trend toward decreased
      blood loss per operated level favoring VATS (68.4 vs. 38.9 cc, p=.09).
      CONCLUSIONS: Both approaches resulted in corrections that compare favorably with
      open thoracotomy. We suggest that a factor in choosing between these two
      minimally invasive techniques is the number of thoracic levels requiring release.
      For four levels or less, MOTA provides an excellent alternative to standard
      thoracotomy. For five or more levels, VATS provides for excellent exposure of
      additional levels with the advantages of less operative time and blood loss per
      operated level.

PMID- 16291103
TI  - Symptomatic cervical disc herniation following a motor vehicle collision: return
      to work comparative study of workers' compensation versus personal injury
      insurance status.
AB  - BACKGROUND CONTEXT: Patients with approved workers' compensation injuries receive
      guaranteed compensation for the duration of their injury, whereas patients with
      personal injury claims are only compensated, if at all, at the time of a
      successful settlement or trial verdict at a time point distant from their injury.
      PURPOSE: This study compares the financial impact and loss of work patterns due
      to a workers' compensation (WC) claim or personal injury in patients with a
      symptomatic cervical disc herniation resulting from a motor vehicle collision.
      STUDY DESIGN: A prospective study of patients who were seen by a single spine
      specialist between 1/2/96 and 9/1/01. PATIENT SAMPLE: A consecutive evaluation of
      531 patients who were treated for a cervical pain syndrome caused by a motor
      vehicle collision. OUTCOME MEASURES: Mechanism of injury and insurance type, ie,
      workers' compensation or personal injury, was recorded for each patient as well
      as treatment response and return to work patterns. The data were analyzed using
      the two-way Z test. METHODS: All patients were managed in a similar manner with
      noninvasive treatment initially, followed by injections, and finally surgical
      intervention in those who failed conservative measures. Return to work rates and
      work disability were determined at either final follow-up or at the last doctor's
      visit before loss to follow-up. RESULTS: 270 of 531 patients were diagnosed with
      a symptomatic one or two level disc herniation by a cervical magnetic resonance
      imaging scan. Fifty-four patients were insured through the workers' compensation
      board, and 216 reported their crash as a personal injury claim. In the WC group
      the work disability at 3 months follow-up revealed a cumulative 2,262 total lost
      days of work (average 37.1 days per person). At the point of maximal medical
      improvement (MMI) or 2-year follow-up, total days lost from work were 7,107
      (average 131.6 days per person.) In the personal injury non-WC group, the 3-month
      follow-up of lost days of work was 1,093 days (average 5.1 days per person.) At 2
      years follow-up, the total lost days of work were 6,206 (average 28.7 days per
      person.) CONCLUSIONS: Participants compensated through the workers' compensation
      system demonstrated a significant loss of days of work as compared with injured
      patients who received compensation by other means. This may be a reflection of
      the guaranteed method of compensation afforded to WC patients as opposed to
      patients who receive no form of financial support (i.e., personal injury) during
      the recuperative process. Further analysis as to injury severity and a
      stratification of non-workers' compensation reimbursement methods are needed to
      further improve the validity of this study.

PMID- 16291105
TI  - Anterior cervical interbody fusion with a titanium box cage: early radiological
      assessment of fusion and subsidence.
AB  - BACKGROUND CONTEXT: The use of stand-alone cervical interbody cages in anterior
      cervical discectomy with fusion (ACDF) has become popular, but high subsidence
      rates have been reported in the literature. PURPOSE: The authors present short
      term radiological results of a titanium box cage with regard to fusion and
      subsidence. Reliable fusion and lack of subsidence may influence long-term
      clinical results. Early radiological data are necessary before implementation of
      this device on a larger scale can be accepted. STUDY DESIGN/SETTING:
      Retrospective radiological quality assessment study. PATIENT SAMPLE: ACDF using
      the titanium cage was performed in 71 consecutive patients at 106 levels.
      Diagnoses included cervical disc disease (57) and cervical spinal stenosis (14)
      after failed conservative treatment. OUTCOME MEASURES: Subsidence and kyphosis
      were assessed on lateral cervical radiographs made directly postoperative and at
      3- and 6-month follow-up. At 6-month follow-up, lateral flexion-extension
      radiographs were made to assess fusion. METHODS: Subsidence of the cage was
      defined as a decrease in total vertical height of the two fused vertebral bodies
      as measured on the lateral cervical radiographs made 3 and 6 months
      postoperatively compared with the directly postoperative radiographs. Segmental
      kyphosis was measured as the angle between the posterior borders of the two
      vertebral bodies on the lateral radiograph. RESULTS: No patients were lost to
      follow-up. Fusion was achieved after 6 months in all patients. At 3 and 6 months
      postoperative the same 10 cages (each in a different patient) had subsided. The
      C6-C7 level was significantly more frequently involved compared with all other
      levels. A segmental kyphotic alignment was observed in five patients at the C6-C7
      level and in one patient at the C4-C5 level. CONCLUSIONS: For patients with
      cervical disc disease, the high subsidence tendency of the cage into the end
      plate of predominantly C7 is a disturbing phenomenon found in this study. A
      modified cage design that improves and extends contact with the inferior surface
      could be expected to reduce subsidence into C7.

PMID- 16291107
TI  - Evaluation of the effect of postural perturbation on motoneuronal activity
      following various methods of lumbar spinal manipulation.
AB  - BACKGROUND AND CONTEXT: One basic physiologic response to spinal manipulation
      (SM) is a transient decrease in motoneuronal activity, as assessed by the
      Hoffmann reflex (H-reflex) technique. However, questions of appropriate control
      procedures when using the H-reflex technique to study the basic physiologic
      mechanisms of SM still exist. The identification of appropriate control
      procedures may allow us to better differentiate among the specific and
      nonspecific aspects of SM. PURPOSE: The purpose of the research was to determine
      the contributions of postural perturbations on the attenuation of motoneuronal
      activity following spinal manipulative thrusts and spinal joint preload
      procedures applied to the lumbar spine. STUDY DESIGN/SETTING: H/M(max) ratios,
      recorded from the gastrocnemius muscle, were measured before and after lumbar
      spinal procedures. The experimental designs for the laboratory data collection
      protocols were repeated measures and between-subjects. PATIENT SAMPLE: The
      subjects were asymptomatic, young, healthy volunteers. OUTCOME MEASURE: H/M(max)
      ratios recorded from the gastrocnemius muscle. METHODS: In Experiment 1, the
      administration of prone lumbar procedures involved either manual assist to more
      fully shear the lumbar zygapophyseal joints or no manual assist. One set of
      subjects (n=17) received assisted joint preload force and manipulation, whereas a
      second set of subjects (n=17) received unassisted joint preload force and
      manipulation. In a second laboratory experiment, one set of subjects (n=10)
      received a L5-S1 side-posture SM, whereas a second set of subjects (n=10) were
      just positioned into side-posture. RESULTS: There was a H/M(max) ratio
      attenuation of 18.2% after assisted spinal manipulation, whereas H/M(max) ratio
      attenuation was only 9.5% after unassisted spinal manipulation. Decreases of
      H/M(max) ratios by 8.5% and 7.5% were observed after assisted and unassisted
      joint preload forces, respectively. The amount of H/M(max) ratio attenuation was
      significantly greater immediately after the L5-S1 SM procedure (28.4%) as
      compared with a side-posture positioning maneuver (15.3%). CONCLUSION: SM may
      provide procedure-specific sensory input that appears to vary, based upon the
      various types of vertebral loading applied to the lumbar spine.

PMID- 16291108
TI  - Nonvascular complications following spinal manipulation.
AB  - BACKGROUND CONTEXT: Spinal manipulation is associated with various vascular and
      nonvascular complications. Most prior studies have focused on the vascular
      complications. PURPOSE: The purpose of this study is to better clarify the
      spectrum of nonvascular complications following spinal manipulation, and to help
      define the risks of manipulative treatment. STUDY DESIGN: Review of medical
      records and radiographic studies of appropriate subjects. PATIENT SAMPLE:
      Patients presenting to a neurosurgical practice over a 6-year period who suffered
      a qualitative worsening of symptoms immediately after spinal manipulative
      treatment. OUTCOME MEASURES: Neurological conditions were compared pre
      manipulation, post-manipulation, and post-surgery. METHODS: Record review of 18
      patients. RESULTS: Eighteen patients were identified who had received spinal
      manipulation and whose neurological condition immediately worsened. Injuries were
      sustained to the cervical, thoracic, and lumbar spine and resulted, variously, in
      myelopathy, paraparesis, cauda equina syndrome, and radiculopathy. Eighty-nine
      percent required surgery. Outcome was excellent in 50% and good in 37.5%. Three
      patients died from unrecognized malignancies. CONCLUSION: Spinal manipulation can
      be associated with significant complications, often requiring surgical
      intervention. Pretreatment scanning may help identify patients with significant
      risk factors, such as substantial disc herniations or occult malignancies. Prompt
      evaluation and intervention is necessary when symptoms worsen or neurological
      deficits develop.

PMID- 16291110
TI  - Radiographic changes induced after cervical facet radiofrequency denervation.
AB  - BACKGROUND CONTEXT: Paraspinal infections after zygapophyseal (facet)
      radiofrequency denervation (RFD) are a serious but rare complication of this
      procedure. We are aware of only one case report of an epidural abscess after
      facet joint injection. PURPOSE: To report post-procedure inflammatory changes
      after cervical facet RFD. STUDY DESIGN: Case report. PATIENT SAMPLE: A 35-year
      old Caucasian female. METHODS: Retrospective case review. RESULTS: The patient
      underwent cervical RFD and was admitted to the hospital 7 days after her
      procedure with severe neck pain. Magnetic resonance imaging (MRI) with contrast
      revealed what appeared to be evidence of a paraspinal muscle abscess although
      blood tests were negative. She was treated with antibiotic therapy, yet she never
      developed systemic signs of infection. A follow-up MRI without contrast revealed
      no evidence of infection, and she was discharged home on hospital day 6. At her
      first follow-up visit, she was still experiencing scalp pain and paraspinal
      muscle spasm. During subsequent follow-up visits, she has continued to improve
      clinically without experiencing signs of infection. Another follow-up MRI 6 weeks
      after her discharge home revealed persistent minimal left paraspinal enhancement
      at C2-3, possibly representing post-procedure granulation tissue with no evidence
      of abscess. CONCLUSIONS: Post-procedural MRI findings after radiofrequency
      lesioning can resemble radiographic findings associated with a paraspinal
      abscess. Patients with radiographic findings consistent with abscess should only
      be treated if clinical signs or symptoms of systemic infection are present.

PMID- 16291111
TI  - A functional classification of spinal instrumentation.
AB  - BACKGROUND CONTEXT: Spinal instrumentation systems have evolved far beyond the
      original Harrington design, with increasing complexity and capabilities. This
      review attempts to de-emphasize the "product names," as systems are often
      generically and inappropriately referred to as "Harrington rods," by introducing
      a functional classification for current systems. PURPOSE: The aim of this paper
      is to review the intended design purpose of current spinal instrumentation
      systems for more accurate interpretations of radiographs and complications. STUDY
      DESIGN: The principles involved in each type of instrumentation system are
      described, followed by the characteristic components and the normal appearance
      radiographically, with examples of complications, which should be recognized.
      METHODS: The historical contribution of specific systems in the developing art of
      internal fixation of the spine is provided as a background to understand the
      biomechanical forces imparted by spinal hardware. Recognizing the functional
      intent of spinal constructs will enhance descriptions of those images. RESULTS:
      Spinal instrumentation has been categorized into five functional types:
      Distraction and compression, segmental stabilization, coupled or derotation
      systems, translational or pedicle screw systems, and anterior instrumentation.
      CONCLUSIONS: Analysis of radiographs from a functional viewpoint can enhance the
      descriptive interpretation and specifically allow assessment of the success or of
      the presence of complications, which are crucial to the analysis of
      instrumentation effectiveness.

PMID- 16291112
TI  - Spinal fluid surgery.

PMID- 16291115
TI  - Animal models for spinal fusion.
AB  - Animal models for spinal fusion are essential for preclinical testing of new
      fusion methods and adjuncts. They allow for control of individual variables and
      quantification of outcome measures. Model characteristics are considered.
      Preclinical experiments to evaluate proof of concept, feasibility, and efficacy
      are generally studied in an orderly progression from smaller to larger animal
      models with an evolving cascade of evidence which has become known as the "burden
      of proof". Methods of fusion analysis include manual palpation, radiographs,
      computed tomography, histology, biomechanical testing, and molecular analysis.
      Models which have been developed in specific species are reviewed. This sets the
      stage for the interpretation of studies evaluating bone graft materials such as
      allograft, demineralized bone matrices, bone morphogenetic proteins, ceramics,
      and others with consideration of the variables affecting their success. As
      evidence accumulates, clinical trials and applications are defined.

PMID- 16291114
TI  - Editorial: are spine biologics the future in spinal surgery?

PMID- 16291116
TI  - Demineralized bone matrix and spinal arthrodesis.
AB  - Spinal fusion is a gold-standard treatment for many disorders of the spine with
      autogenous bone graft as the gold-standard source for augmenting fusion. However,
      the morbidity and limitations of autogenous bone grafting has motivated the
      search for bone graft alternatives. One such alternative is demineralized bone
      matrix (DBM). The purpose of this paper is to describe and characterize the
      properties of DBM in addition to reviewing the results of its use in animal and
      human studies of spinal fusion. A thorough and critical review of the English
      language literature was conducted. DBM is both osteoconductive and
      osteoinductive. Studies have produced variable results with respect to spinal
      fusion rates. Various studies have demonstrated inferior, equal, or enhanced
      fusion rates. Some of the differences in these studies include the animal models
      used, the manner in which DBM was prepared, and the carrier with which DBM was
      combined. These differences may account for the dissimilar results. DBM is able
      to function as a graft extender in the human species.

PMID- 16291117
TI  - Carrier materials for spinal fusion.
AB  - BACKGROUND CONTEXT: The rise in spinal fusion procedures has led to an increase
      in the available number and variety of bone graft substitutes. As our
      understanding of the biologic processes that influence bony fusion has improved,
      appreciation for the role of the carrier material involved in bone grafts has
      also increased. PURPOSE: The abundance of products available leaves a surgeon
      with many choices. Knowledge of the current advances will allow for more critical
      review of the literature and improved decision making when choosing bone graft
      materials. STUDY DESIGN/SETTING: Review of the English-language literature.
      METHODS: A critical review of basic science, animal and human studies that
      investigate the types and role of carrier materials used in spine surgery.
      RESULTS: The myriad of carrier material available to the spine surgeon is related
      to the many options in bone graft material. Allograft is an important
      osteoconductive agent but has its disadvantages especially in regard to disease
      transmission and immunogenicity. Collagen in various forms is an effective
      carrier for bone morphogenic protein and autogenous stem cells and can be easily
      combined with other bone graft materials. Synthetic options include
      hydroxyapatite and calcium phosphate ceramic materials with different
      formulations; all are osteoconductive only but can be combined with
      osteoinductive and/or osteogenic components. Bioabsorbable carriers are effective
      for use with bone morphogenic protein and can also be used in multiple forms and
      settings. CONCLUSIONS: Many bone graft carriers exist, and multiple studies have
      shown their efficacy. It appears that no one carrier is ideal but each situation
      might influence the choice of one carrier over another.

PMID- 16291118
TI  - Cell technologies for spinal fusion.
AB  - For a successful spinal fusion to occur, several vital elements are necessary.
      They consist of the presence of the bone-forming cell (osteoblast) or its
      precursor, the appropriate biological signals directing bone synthesis, and a
      biocompatible scaffold on which the process can occur. The most critical of these
      components is the osteoblast or its precursor, the mesenchymal stem cell (MSC),
      both of which possess the ability to form bone. As a result, many current
      techniques attempt to maximize the benefits derived from harvesting the ready
      source of MSCs from bone marrow, while minimizing the associated complications.
      These cellular technologies seek to improve on the harvest and concentration of
      the MSCs or enhance their delivery and action. This review focuses on the
      terminology, historical underpinnings, and current research rationale and
      techniques and discusses the possible future of these technologies.

PMID- 16291119
TI  - Bone morphogenetic proteins for spinal fusion.
AB  - BACKGROUND CONTEXT: In 1965, Marshall Urist discovered that the extracellular
      matrix of bone contains the ability to induce new bone formation. This substance
      was later named bone morphogenetic protein (BMP). Since that time, BMPs have been
      extensively studied. Molecular clones have since been characterized and expressed
      as complementary DNAs (cDNAs). BMPs have recently been used in a multitude of
      mammalian clinical studies, including many recent human studies, for the purpose
      of evaluating their function in bone healing and spinal arthrodesis. BMPs are
      currently the most effective substitute available for bone graft as a means to
      eliminate the morbidity of iliac crest bone graft harvest and increase the rate
      of successful spinal arthrodesis. PURPOSE: The purpose of this article is to
      review the history and recent advancements in the use of BMPs in spinal
      arthrodesis models, as well as discuss the possible future use of BMPs in this
      clinical setting. STUDY DESIGN/SETTING: The setting of this review article is
      centered on classic and recent literature of BMPs with emphasis on anterior as
      well as posterolateral spinal arthrodesis. METHODS: The classic and recent
      primary literature about BMPS and their clinical use in human and nonhuman
      mammals for spinal fusion was reviewed. Special emphasis is placed on animal and
      human studies of both recombinant human bone morphogenetic protein-2 (rhBMP-2)
      and recombinant human osteogenic protein-1 (rhOP-1, rhBMP-7). RESULTS: BMPs are
      able to promote solid fusion in the spine in both the anterior and the
      posterolateral environments in animal studies and early human trials. Human
      trials to date have also shown an acceptable safety profile with the clinical use
      of these proteins. CONCLUSIONS: Animal studies and early human trials of BMPs
      support the ability of these growth factors to enhance or replace autograft bone
      for spinal arthrodesis. Studies have shown this promotion of fusion in both the
      anterior interbody and the posterolateral environments. Future use of these
      factors is likely to continue to expand in clinical as well as research arenas.

PMID- 16291121
TI  - Summary statement: biologics for spine fusion.

PMID- 16291120
TI  - Gene therapy for spinal fusion.
AB  - Spinal fusion will continue to be an important part of the surgical treatment of
      spinal pathology for the foreseeable future. Traditional challenges to successful
      spinal fusion surgery include autograft donor site morbidity and pseudoarthrosis.
      Recent advances in the understanding of the biology of bone formation have
      allowed the development of therapeutic biologics. Although recombinant bone
      morphogenetic proteins delivered to the arthrodesis site will stimulate fusion,
      these proteins have been less successful in more challenging fusion situations
      (posterolateral), require supraphysiologic doses to promote fusion in humans, and
      are quite expensive. Gene therapy may represent the easiest method for the
      application of bone-forming biologic agents to promote spinal fusion. Both in
      vivo and ex vivo techniques of delivery of therapeutic genes have been used
      effectively to promote fusion in lower animals. Considerable research is required
      to identify gene therapy techniques and vectors with acceptable safety profiles
      and high fusion rates.

PMID- 16291122
TI  - Molecular pathogenic factors in symptomatic disc degeneration.
AB  - BACKGROUND CONTEXT: Although symptomatic disc degeneration is thought to be the
      leading cause of chronic low back pain, no available biologic therapy is yet
      available to treat this highly prevalent condition. PURPOSE: In this article, the
      cellular, biomechanical and molecular alterations that occur during disc
      degeneration are reviewed to provide a better understanding of this pathologic
      process. STUDY DESIGN: The cellular and molecular aspects of disc degeneration
      are reviewed. METHODS: The available studies detailing the molecular and cellular
      changes during disc degeneration are reviewed in an effort to provide a basis for
      understanding the biologic strategies for disc repair. RESULTS: Disc degeneration
      begins early in life and involves a cascade of changes at the cellular and
      molecular level that results in degradation of the extracellular matrix of the
      disc, leading to biomechanical failure of this complex structure. CONCLUSION:
      With a thorough understanding of the cellular and molecular events causing
      degeneration of the intervertebral disc, rational strategies for disc repair can
      be understood and evaluated. It appears that biologic disc repair will be
      feasible in the future although challenges remain in this blossoming field.

PMID- 16291124
TI  - Molecular therapy of the intervertebral disc.
AB  - BACKGROUND CONTEXT: Currently, no biologic treatment is available for disc
      degeneration. However, many different molecules of potential therapeutic benefit
      are being investigated. PURPOSE: Review and categorize the molecules under
      investigation for potential therapy in preventing or reversing disc degeneration.
      STUDY DESIGN: Review article. METHODS: Review of published articles on molecules
      that may be useful in biologic therapy of the intervertebral disc. RESULTS: The
      list of molecules under investigation for potential benefit in biologic therapy
      of the intervertebral disc repair continues to grow. These molecules are so
      diverse that they no longer all fall into the classic terminology of "growth
      factor." Some of these molecules are not growth factors at all and some are not
      even cytokines. At least four different classes of molecules may be effective in
      disc repair. These include anticatabolics (eg, tissue inhibitors of
      metalloproteinase [TIMPs]), mitogens (eg, insulin-like growth factor-1 [IGF-1],
      platelet-derived growth factor [PDGF]), chondrogenic morphogens (transforming
      growth factor beta [TGF-beta] and bone morphogenetic proteins [BMPs]), and
      intracellular regulators (LIM mineralization protein-1 [LMP-1] and Sox9).
      Although some in vitro data are available on all of these molecules, few of these
      molecules have been tested in vivo with an animal model of disc degeneration.
      CONCLUSIONS: As the current screening experiments are concluded, more definitive
      in vivo systems involving a more realistic degeneration model will be a necessary
      step before attempting human studies.

PMID- 16291123
TI  - Animal models for human disc degeneration.
AB  - Despite the significant impairment associated with degenerative disc disease, a
      clear understanding of its pathogenesis is still lacking. Currently, no
      particular model parallels the complex nature of human disc degeneration.
      Naturally occurring animal models have the drawback that the basis for the high
      rate of disc degeneration is not known. Although the interventions in artificial
      animal models that create disc degeneration are known, the relationship of those
      to the events leading to disc degeneration in humans is not. With the recent
      progress in biomechanics, cell biology and molecular biology, an easily
      reproducible and valid animal model may help unlock the complex cascade of events
      surrounding human disc degeneration.

PMID- 16291125
TI  - Gene therapy for disc repair.
AB  - BACKGROUND CONTEXT: Recent advances in our understanding of the biologic makeup
      and environment of the intervertebral disc (IVD) have led to increased interest
      in the development of novel treatments for disc degeneration. Certain genes found
      to alter rates of matrix synthesis and catabolism within the disc have provided
      targets for scientists seeking to alter the balance between the two. To this end,
      gene therapy has emerged as a potential therapeutic option, and recent research
      efforts have yielded very promising results. PURPOSE: To update and consolidate
      information regarding the recent advances in gene therapy and its application to
      IVD degeneration. STUDY DESIGN/SETTING: Review of recent and ongoing research in
      the field of gene therapy, particularly regarding its application to the
      treatment of IVD degeneration. METHODS: Literature review. RESULTS: With its
      unique ability to provide sustained delivery of potentially therapeutic agents,
      gene therapy has shown much promise with regard to the treatment of IVD
      degeneration. There have been many exciting developments such as safer and more
      reliable vector constructs, favorable results using therapeutic transgenes in
      disc cells both in vitro and in vivo, and improvement in transgene regulation,
      and investigators continue to explore ways in which gene therapy can become a
      powerful tool in the future treatment of disc degeneration. CONCLUSIONS: With
      continued perseverance and dedication, many advances have been made in the
      application of gene therapy to the IVD, and it continues to demonstrate great
      potential to become a powerful tool in the future treatment of disc degeneration.

PMID- 16291126
TI  - Cell-based therapy for disc repair.
AB  - BACKGROUND CONTEXT: One of the most promising therapies for symptomatic disc
      degeneration involves the implantation of therapeutic cells into the degenerative
      disc. PURPOSE: In this article, the rationale and approaches for cell-based
      tissue engineering of the intervertebral disc are discussed. STUDY DESIGN: The
      scientific literature related to cell-based tissue engineering of the
      intervertebral disc is reviewed. METHODS: A variety of cell types have been used
      in various research models to affect matrix repair of the intervertebral disc.
      The use of cellular scaffolds and growth factors or genes also appears promising
      for achieving meaningful tissue repair of the intervertebral disc. RESULTS: Disc
      tissue engineering is a promising approach for achieving repair of the
      intervertebral disc. Using cell-based approaches, various research models suggest
      that improvements in the complex matrix of the disc may be achieved. CONCLUSION:
      A cell-based approach to repair of the intervertebral disc appears promising.
      More research is needed to define the optimal cell type, cellular scaffold and
      mixture of growth factors that may allow meaningful repair of the human
      symptomatic degenerative disc.

PMID- 16291127
TI  - Summary statement: biologic repair or regeneration of the intervertebral disc.

PMID- 16291128
TI  - Vertebroplasty and kyphoplasty: filler materials.
AB  - Over 700,000 osteoporotic compression fractures occur each year in the United
      States, twice the number of hip fractures. These vertebral fractures, most of
      which occur in the elderly, represent significant personal and societal burdens.
      Percutaneous vertebroplasty (PVP) is a minimally invasive method that involves
      the percutaneous injection of polymethylmethacrylate (PMMA) into a collapsed
      vertebral body to stabilize the vertebra. Kyphoplasty is an advanced minimally
      invasive technique with a number of potential advantages over PVP, including
      lower risk of cement extravasation and better restoration of vertebral body
      height and spinal biomechanics. The filling materials used for both these
      techniques require good biocompatibility, good biomechanical strength and
      stiffness, and good radiopacity for the fluoroscopy guided procedures. New filler
      materials (synthetic bone substitutes, e.g., composite resin materials, calcium
      phosphate or calcium sulfate cements) in addition to new PMMA formulations are
      now available for clinical use. In this review paper, we will focus on the issues
      and characteristics of these filler materials as they pertain to vertebral
      augmentation procedures.

PMID- 16291129
TI  - Nucleus pulposus replacement: an emerging technology.
AB  - Debilitating low back pain as a result of symptomatic lumbar disc degeneration
      places a significant burden on an industrial society. Traditionally surgical
      treatment involving fusion of the anterior and posterior spinal elements has
      resulted in unpredictable and frequently irreproducible results, especially with
      regard to return to work rates. A new surgical method of managing symptomatic
      disc degeneration recalcitrant to nonoperative measures involves the partial or
      complete removal of the intervertebral disc with replacement with a motion
      sparing device. A review of the English-speaking literature will be discussed
      evaluating the historical development, design considerations, animal models,
      basic science studies, cadaveric research, and clinical outcomes of the partial
      removal of the intervertebral disc (nucleus pulposus) and replacement with a
      motion-sparing implant. An overview of traditional methods of surgical management
      of lumbar degenerative disc disease will then be followed by an introduction to
      the concept of motion-sparing implants (nucleus pulposus replacement) intended to
      remove the pain generator without the associated morbidity of a surgical fusion.

PMID- 16291130
TI  - Summary statement: kyphoplasty and nucleus pulposus prosthesis.

PMID- 16291131
TI  - Fracture and retrosternal dislocation of the medial clavicle in a 12-year-old
      child--case report, options for diagnosis, and treatment in children.
AB  - We report a retrosternally displaced epiphysiolysis in a 12-year-old child and
      discuss options for the most appropriate diagnostic and therapeutic approach. If
      a standard anteroposterior view of the shoulder girdle shows abnormalities or if
      appropriate clinical suspicion is present, we strongly favor an magnetic
      resonance imaging study for further workup instead of a computed tomographic
      scan, which is currently the diagnostic method of choice in clinical algorithms.
      Radiation exposure is thereby limited and maximum information about possible
      mediastinal soft tissue complications is obtained using a single diagnostic tool.
      If open reduction is indicated, retention of the joint or approximation of
      physeal fracture or treatment of ligamentous injury should be performed without
      metal devices. These suggestions for future management of these patients should
      further reduce the use of x-rays in children. In addition, applying a suture
      instead of using metal for stabilization can avoid the extensively described
      complications in literature that can potentially result from metal devices. In
      addition, sutures circumvent the need for a second operation for metal removal.

PMID- 16291132
TI  - Azygos lobe associated with esophageal atresia: a trap for the unwary.
AB  - Presence of an associated azygos lobe may cause problems during thoracotomy on
      the right side for esophageal atresia. Awareness of the anomaly allows its
      recognition and appropriate management.

PMID- 16291134
TI  - Multiple lymph node metastases in a boy with primary testicular carcinoid,
      despite negative preoperative imaging procedures.
AB  - A testicular tumor in a 12-year-old boy proved to be a carcinoid tumor. An
      extensive investigation including a computed tomographic scan of the abdominal
      and pelvic region as well as both 123I-labeled metaiodobenzylguanidine and 111In
      coupled octreotide scintigraphy was normal. Because histopathologic examination
      of the primary surgical specimen revealed tumor growth in the resection border of
      the spermatic vessels, a second operation with unilateral lymph node dissection
      was performed. Surprisingly, 3 lymph node metastases were found. No further
      treatment was given and the boy is alive without disease 9 years after surgery.
      This case illustrates that modern scintigraphic techniques do not always detect
      carcinoid tumors. Because carcinoids respond poorly to other treatment
      modalities, the importance of initial radical surgery including a meticulous
      examination of regional lymph nodes is emphasized.

PMID- 16291133
TI  - Laparoscopic cystogastrostomy for the treatment of pancreatic pseudocysts in
      children.
AB  - Pancreatic pseudocysts (PPSs) are common sequelae of pancreatitis and pancreatic
      trauma. The management is based upon the pseudocyst size and presence of
      symptoms. Those requiring intervention are often drained using several available
      options. The use of laparoscopic cystogastrostomy for large and recurrent PPSs
      has been described in adult patients as a less morbid alternative to open
      drainage procedures. This technique is considered a novel approach in children.
      We describe 2 children who had PPSs amenable to laparoscopic cystogastrostomy.
      The first was an 11-year-old girl who had blunt abdominal trauma from a bicycle
      handlebar. The second patient was a 7-year-old girl who developed idiopathic
      pancreatitis. Briefly, 2 ports were placed through the anterior abdominal and
      gastric walls, and into the lumen of the stomach. This intraluminal placement
      provided access to the posterior gastric wall. Using electrocautery diathermy, an
      incision was made through the posterior gastric wall and into the adjacent
      pseudocyst to obtain complete and unobstructed drainage. Both children tolerated
      the procedures well with resolution of their PPSs. The patients were each
      discharged on the fourth postoperative day and have been asymptomatic on 2 years
      follow-up. Laparoscopic cystogastrostomy is a safe and effective alternative to
      open cystogastrostomy for the minimally invasive management of PPSs in the
      pediatric population.

PMID- 16291135
TI  - Idiopathic benign bilateral testicular enlargement in a pubertal boy: a case
      report and review of literature.
AB  - We present a case of 12-year-old boy with idiopathic benign bilateral testicular
      enlargement. We eliminated precocious puberty, juvenile hypothyroidism, adrenal
      rest tumors, X-linked mental retardation, and bilateral testicular neoplasms. The
      clinical and laboratory features and differential diagnosis of benign bilateral
      testicular enlargement are discussed.

PMID- 16291136
TI  - The second and third right posterior intercostal veins: an alternate route for
      central venous access with an implantable port in children.
AB  - BACKGROUND/PURPOSE: Some children dependent on total parenteral nutrition for
      long periods have no more axillary, internal jugular, external jugular,
      saphenous, and femoral veins available for cannulation. In such patients, the
      central venous system can still be accessed via the azygos vein by placing an
      implantable port catheter through one of the right posterior intercostal veins.
      This is the first known description of such procedure. METHODS: We report the use
      of the second and third right intercostal veins for placement of the catheter by
      right intrapleural thoracotomy in 2 pediatric patients with short gut syndrome.
      RESULTS: Recovery from the thoracotomy was uncomplicated, and the patients could
      receive complete intravenous nutritive mixtures immediately after the insertion
      of the catheter. Both patients remain dependent on total parenteral nutrition and
      are awaiting an intestinal transplantation. CONCLUSION: The knowledge of
      alternate routes to obtain central venous access for prolonged parenteral
      nutrition is critically important, and the azygos system can be used when more
      accessible veins are unavailable.

PMID- 16291137
TI  - The impact of 3-dimensional ultrasonography on perinatal management of a large
      epignathus teratoma without ex utero intrapartum treatment.
AB  - We report a case of epignathus teratoma diagnosed at 22 weeks of gestation in
      which 3-dimensional ultrasound (3DUS) was useful to plan perinatal management. A
      significant enlargement of the tumor, associated with polyhydramnios and preterm
      labor, was observed at 35 weeks of gestation. After amniotic fluid evacuation,
      3DUS was performed in the presence of pediatricians, obstetricians, and
      otolaryngologists. Three-dimensional ultrasound revealed that great part of the
      tumor was located outside the fetal mouth and anterior to fetal mandible,
      suggesting that the newborn could breathe spontaneously by nasal via. A cesarean
      section with longitudinal hysterotomy was performed at 36 weeks followed by an
      immediate extirpation of the tumor and the intubation of the newborn. The
      management of this rare case illustrates that the ex utero intrapartum treatment
      (EXIT) procedure is not always necessary in this situation. Besides, the actual
      prenatal goal consists on carefully selecting fetuses with epignathus teratoma
      that will need the EXIT procedure from those that will not. Three-dimensional
      ultrasound and magnetic resonance imaging in association with 2DUS can be helpful
      in this prenatal selection.

PMID- 16291138
TI  - Inflammatory myofibroblastic tumor of renal pelvis presenting with prolonged
      fever and abdominal pain in children: report of 1 case and review of literature.
AB  - Inflammatory myofibroblastic tumor is a reactive proliferative lesion that occurs
      extremely rarely in the renal pelvis, especially during childhood. We report 1
      such case that occurred in a child who presented with prolonged fever and
      abdominal pain. Ultrasonography and abdominal computed tomography revealed a left
      renal pelvic mass. She received conservative surgical treatment. The diagnosis
      was confirmed by pathological and immunohistochemical studies. Distinguishing
      inflammatory myofibroblastic tumor from other malignant renal pelvic tumors in
      children is essential to preventing unnecessary nephrectomy.

PMID- 16291139
TI  - Acute abdominal pain in a separated conjoined twin.
AB  - Complications of conjoined twins are typically events surrounding the birth and
      surgical separation. We report an unusual late-onset complication, a grade IV
      duodenal disruption of the accessory system in a formerly conjoined twin. Because
      conjoined twins have unique anatomy based on the junction and division of organs,
      one must always consider a multitude of causes for common complaints. Basic
      operative principles apply: the acute abdomen must be explored. Finally, to avoid
      these complications, removal of all or nearly all parasitic structures must be
      considered at the initial separation.

PMID- 16291140
TI  - A case of intrapericardial diaphragmatic hernia with a massive pericardial
      effusion: fetal diagnosis and therapy.
AB  - Intrapericardial diaphragmatic hernia is a very rare phenotype of neonatal
      diaphragmatic hernia which is thought to be caused by the developmental failure
      of the septum transversum. There have been only 10 cases reported since 1980, and
      among them, only 2 cases were diagnosed in fetal life. We herein report a new
      case that was diagnosed in fetal life, and pericardiocentesis was performed at 27
      weeks of gestation. This is the first case to undergo a fetal interventional
      therapy. After birth, the patient successfully underwent closure of the hernia,
      despite severe pulmonary hypoplasia.

PMID- 16291141
TI  - Williams-Beuren syndrome associated with caudal regression syndrome and
      coagulopathy--a case report.
AB  - Williams-Beuren syndrome is a genetic disorder caused by a heterozygous deletion
      at 7q11.23. The present report describes a female patient with Williams-Beuren
      syndrome combined with caudal regression syndrome and two forms of coagulopathy.
      Besides the typical developmental abnormalities such as mental and growth
      retardation, a distinctive facial appearance, and cardiovascular anomalies, our
      patient showed fusion of fourth and fifth lumbar vertebra and a sacrococcygeal
      agenesis. Blood coagulation tests revealed a deficiency of coagulation factor XI
      and XII. Magnetic resonance imaging angiography showed multiple vascular stenoses
      mainly in the abdominal aorta and its major branches as a consequence of the
      insufficient elastin gene. Previous reports identified a deletion of HLXB9 as a
      possible genetic cause of the caudal regression syndrome, which could not be
      identified in the present case. This unusual combination of the above-mentioned
      genetic disorders has not been published so far.

PMID- 16291142
TI  - Delayed near-fatal hemorrhage after Nuss bar displacement.
AB  - A novel case of Nuss bar displacement with near-fatal hemorrhage 3 months after
      insertion and 3 weeks after unreported bar movement is presented. Salient
      features of presentation, evaluation, and treatment are described including how
      to divide the bar from an intrathoracic approach.

PMID- 16291143
TI  - Ciliated hepatic foregut cyst in a young child.
AB  - Ciliated hepatic foregut cysts are a rare entity usually found in adults. We
      present a case of a 3-year-old boy incidentally noted to have a radiographically
      complex liver cyst on computed tomographic scan. Given the complex appearance,
      the cyst was excised. Pathology revealed a ciliated hepatic foregut cyst. This is
      the second child and youngest patient affected with this lesion reported in the
      literature. The etiology of the lesion and an argument for surgical removal in
      pediatric patients are presented.

PMID- 16291144
TI  - Hemothorax: an unusual complication of costal exostosis.
AB  - We report a case of a spontaneous hemothorax in a 15-year-old girl because of
      costal exostosis. This possibly may have been provoked by a nontraumatic rupture
      of markedly dilated pleural vessels because of long-standing friction between the
      exostosis and the pleura. The authors conclude that exostosis of the rib is a
      rare cause of hemothorax in children and should be considered among possible
      etiologies in diagnosis.

PMID- 16291145
TI  - Chronic intestinal bleeding because of aneurysm of superior pancreaticoduodenal
      artery: embolization during angiography.
AB  - A case of gastrointestinal hemorrhage, associated with abdominal pain, in an 8
      year-old child because of an arterial malformation of duodenum is reported.
      Selective arteriography showed the presence of an aneurismatic lesion of superior
      pancreaticoduodenal artery. The leakage of the vascular lesion during examination
      permitted the embolization by microcoils and cyanoacrylate glue. The follow-up by
      computed tomography scan revealed a complete occlusion of the lesion.

PMID- 16291146
TI  - Nonoperative management of pediatric splenic injury with angiographic
      embolization.
AB  - A 12-year-old girl was admitted after a bicycle accident, and a grade 4 splenic
      injury was diagnosed. She became hemodynamically unstable within the first hours
      after arrival and remained so despite fluid resuscitation and transfusions. As an
      alternative to laparotomy, splenic artery embolization was performed. The patient
      had an uneventful recovery without the need for further transfusions.
      Nonoperative management of blunt splenic trauma remains the gold standard in
      pediatric trauma care. In hemodynamically unstable patients, splenic artery
      embolization should be considered as an adjunct to that strategy.

PMID- 16291147
TI  - Renal artery pseudoaneurysm secondary to blunt trauma treated with microcoil
      embolization.
AB  - BACKGROUND: Renal artery pseudoaneurysms are rarely described sequelae of blunt
      abdominal trauma. Interventional radiological advances have allowed such lesions
      to be managed nonoperatively. METHODS: The authors review the presentation,
      diagnostic evaluation, and hospital course of an 11-year-old girl who developed a
      right renal artery pseudoaneurysm 14 days after blunt abdominal trauma. RESULTS:
      An 11-year-old girl fell off a horse onto her right flank. She sustained multiple
      right hepatic lobe lacerations and a complex fracture of the upper pole of the
      right kidney. Her initial hospital course was uncomplicated, and she was
      discharged after an uneventful 6-day course. The child did well for 2 weeks,
      until she developed right back pain and gross hematuria. A computed tomography
      scan revealed a right renal artery pseudoaneurysm. Angiography confirmed the
      presence of a pseudoaneurysm, which was fed by a single segmental branch
      originating from the renal artery. The artery was successfully occluded with a
      single platinum microcoil, which was demonstrated by the absence of contrast flow
      into the pseudoaneurysm. The patient recovered and was discharged shortly after
      the procedure. She initially had intermittent pain and hematuria, which resolved.
      Follow-up computed tomography scans have shown resolution of both the renal and
      hepatic lesions. CONCLUSIONS: Renal artery pseudoaneurysms that arise after blunt
      abdominal trauma in the pediatric population may be safely and effectively
      managed with arterial embolization, thereby avoiding extensive surgical
      interventions.

PMID- 16291148
TI  - Acute pancreatitis in a young girl with the Netherton syndrome.
AB  - Acute pancreatitis is uncommon in children younger than 15 years. We present the
      first report on the association of acute pancreatitis with the Netherton
      syndrome. The Netherton syndrome is an inherited skin disease characterized by
      ichthyosiform erythroderma, a pathognomonic hair shaft defect ("bamboo hair"),
      and atopic features. A 14-year-old girl with symptoms and signs of severe acute
      pancreatitis was admitted to our department. A diagnostic workup could not reveal
      any common known cause of pancreatitis, and the cause of pancreatitis would most
      likely be considered idiopathic. However, based on recent reports regarding
      various pathophysiological mechanisms for both acute pancreatitis and the
      Netherton syndrome (eg, shearing the 5q locus for the respective gene-associated
      defects in SPINK1 and SPINK5), we speculate if a possible association may exist.
      Investigations on pancreatitis and the Netherton syndrome may disclose factors
      closely involved in the pathomechanisms of both. This notion may be of clinical
      importance as it adds to the number of potential life-threatening events to
      patients with the Netherton syndrome.

PMID- 16291149
TI  - Complications of the minimally invasive repair of pectus excavatum.
AB  - BACKGROUND: Minimally invasive repair of pectus excavatum (MIRPE) has become
      widely popular since its introduction in the late 1990s by Nuss. We describe 1
      unusual complication after MIRPE and 1 life-threatening bleeding during removal
      of the pectus bar. METHODS: We report the cases of 2 patients in a single
      institution, more than 100 MIRPE procedures performed so far, and review of
      literature. CASES: A 14-year-old girl presented 6 months after MIRPE in another
      institution. During removal of the pectus bar, a massive hemorrhage from both
      chest wounds occurred, requiring emergency sternotomy. Arrosion of a pulmonary
      vessel close to the metal bar had led to the bleeding. The second case was a
      bilateral sternoclavicular dislocation after MIRPE, which has not caused symptoms
      so far, in a 13-year-old girl. CONCLUSIONS: Numerous operative and postoperative
      complications after MIRPE are feasible. This is the first report of a life
      threatening bleeding during removal of the pectus bar. Minimally invasive repair
      of pectus excavatum procedure and removal of the pectus bar should only occur in
      specialized institutions with wide experience in thoracic surgery.

PMID- 16291150
TI  - Urethral polyp in neonate: a rare occurrence.
AB  - Polyps of urethra as well as those in an anterior urethra in a male neonate are a
      rare abnormality, hence this publication. They usually present as either
      obstructive urinary symptoms in males or as an intralabial mass in females (Raviv
      G, Leibovitch I, Hanani J, et al., Hematuria and voiding disorders in children
      caused by congenital urethral polyps: principals of diagnosis and management. Eur
      Urol 1993;23:382.

PMID- 16291151
TI  - Congenital heart defect with associated malformations in children.
AB  - BACKGROUND: Children with multisystem involvement including congenital heart
      defect (CHD) are a very salient problem. The purpose of this study was to
      evaluate the incidence of CHD associated with malformations of other systems and
      to assess the modalities of treatment and perioperative mortality among patients
      referred to the department of pediatric cardiac surgery. METHODS: The medical
      records of 1856 children were reviewed retrospectively from 1997 to 2002 to
      establish CHD and types of associated malformations. The connections between CHD
      and other lesions were investigated. Furthermore, the influence of patient and
      perioperative variables on mortality risk was scrutinized. Univariate and
      multivariate analyses were used. RESULTS: Eighty-four children (4.53%) had CHD
      and associated malformations. The malformations of digestive (35.7%), urinary
      (22.4%), and nervous (14.3%) systems were the most frequently observed associated
      defects. No relation was found between CHD and concomitant lesions. The results
      of multivariate logistic regression showed significant influence of patient age,
      primary cardiac procedure, and CHD type on mortality (ca 19%) in children with
      multiorgan lesions. CONCLUSIONS: The treatment of children with CHD and
      associated multiple lesions is connected with higher mortality risk. The
      following factors: younger age, urgency of surgical procedure, and primary
      surgical procedure had negative impact on patient's outcome. However, these risks
      in certain cases are inevitable. The cardiac procedure preceding the surgical
      operation may improve the overall effect of treatment because of circulatory
      stabilization, provided that the condition of the patient does not preclude any
      intervention at all.

PMID- 16291152
TI  - Mesenchymal hamartoma of the liver: a systematic review.
AB  - Mesenchymal hamartoma of the liver is the second commonest benign liver tumor in
      children, yet its biology and pathogenesis are poorly understood. Cytogenetic
      studies have suggested that the tumor may be a neoplasm rather than a hamartoma.
      Typically, it presents as a large benign multicystic liver mass in a child
      younger than 3 years amenable to complete resection. However, its imaging
      characteristics are variable, ranging from a few large cysts to a solid mass
      occupying one or both lobes of the liver. In addition, the tumor occasionally
      contains angiomatous elements or is multifocal. Most tumors gradually increase in
      size, some reaching enormous proportions, which can make surgery challenging.
      Paradoxically, a few undergo incomplete spontaneous regression and, on rare
      occasions, others have shown malignant transformation to undifferentiated
      (embryonal) sarcoma. These unusual pathological and biological features must be
      taken into account when considering the management of affected individuals.

PMID- 16291153
TI  - Predictors of outcome in children and adolescents with rhabdomyosarcoma of the
      trunk--the St Jude Children's Research Hospital experience.
AB  - PURPOSE: The aim of this study was to determine predictors of outcome in
      childhood truncal rhabdomyosarcoma. METHODS: Retrospective chart review
      evaluating the impact of demographic features, disease characteristics, and the
      extent and timing of surgical intervention on outcome was performed. RESULTS:
      Thirty-three patients with a median age of 8 years were identified. Most had
      advanced Intergroup Rhabdomyosarcoma Study group III (n = 13) or group IV (n = 9)
      disease. Primary site included 20 (61%) chest wall, 6 (21%) paraspinal, 5 (15%)
      periscapular, and 1 (3%) abdominal wall. Most tumors were embryonal (n = 21),
      larger than 5 cm (n = 27), and locally invasive (n = 13); 7 had positive nodes.
      Tumor size, nodal status, and gross total tumor resection (upfront or delayed)
      were significant predictors of event-free and overall survival. Tumors 5 cm or
      smaller were amenable to upfront surgical resection (P = .007). In patients with
      tumors larger than 5 cm, resection at any time was associated with a 10-year
      overall survival 57% +/- 13% compared with 8% +/- 5% in those who had no surgery
      (P = .003). Tumor recurrence was local in 44% of cases, and survival after local
      recurrence was rare (1 of 8). CONCLUSION: Tumor size, nodal status, and gross
      total resection at any time are significant predictors of outcome in truncal
      rhabdomyosarcoma. Gross tumor excision should be the goal of surgical
      intervention in this disease.

PMID- 16291154
TI  - The role of a more extensive surgical approach in the initial multimodality
      management of papillary thyroid cancer in children.
AB  - PURPOSE: Papillary thyroid cancer (PTC) in children is rare. The optimal initial
      surgical treatment remains controversial, given the generally favorable overall
      prognosis but high rate of cervical metastasis and local recurrence. Our
      objective was to examine the surgical outcomes of a policy of total thyroidectomy
      and routine selective lymph node dissection (SLND) as the initial surgical
      approach to children with PTC. METHODS: This is a retrospective cohort study
      comprising 14 children (age, < or =17 years) with PTC referred for thyroid
      surgery during the past 15 years. Clinical presentation, the surgical procedure,
      final pathology, lymph node involvement, complications, and recurrence rates are
      reported. RESULTS: There were 9 females and 5 males, with an average age of 12.5
      years. Seven patients (50%) had clinically apparent cervical lymphadenopathy at
      the time of surgical referral. All subjects underwent total thyroidectomy, and 12
      (86%) had SLND. Of the 12 who underwent SLND, 10 (83%) had nodal metastases.
      Temporary hypocalcemia was noted in 3 of the patients (21%), and 1 patient has
      required ongoing intermittent calcium supplementation. All patients are alive and
      well at follow-up with no clinical, biochemical, or radiological evidence of
      local recurrence. CONCLUSIONS: Total thyroidectomy with initial SLND is an
      appropriate surgical approach in children with PTC. It can be done without a
      significantly increased risk for permanent complications and may reduce the
      requirement for subsequent surgical intervention for local recurrence in this
      young population.

PMID- 16291155
TI  - Implantation of a cone-shaped double-fixed patch increases abdominal space and
      prevents recurrence of large defects in congenital diaphragmatic hernia.
AB  - BACKGROUND: Large defects in patients with congenital diaphragmatic hernia (CDH)
      are frequently closed with a polytetrafluoroethylene patch (PTFE). Intraoperative
      problems include lack of abdominal domain for the reduction of organs and closure
      of the abdominal wall. Main surgical postoperative complication is the recurrence
      of the hernia. We suggest a new and easy method of patch implantation, improving
      these problems, and report first follow-up results. METHODS: In our clinic, 103
      children with CDH were treated, and 87 children underwent reconstruction of the
      diaphragm in the 5 years between 1998 and 2002. In 52 patients, a patch
      implantation had to be performed. We have been optimizing our complete pediatric
      and surgical procedure and present a new standardized technique of preparation
      and implantation of a PTFE patch. The flat patch is folded to a 90 degrees cone.
      The cone is fixed in its form with few single stitches. It is implanted with an
      overlapping border of 1 cm circumferentially. The border is separately fixed with
      absorbable single stitches to keep from rolling up. The rough side of the patch
      points toward the rim of the diaphragm to enable ingrowth of the connective
      tissue. In a 1-year follow-up study, the recurrences in the 3 following groups of
      PTFE patches were studied: conventional implantation (simple patch without
      overlapping border), patch with separately fixed overlapping border, and cone
      shaped patch with overlapping separately fixed border. RESULTS: Thirty-three
      patients were included in the study. After conventional PTFE-patch implantation,
      6 (46%) of 13 patients developed reherniation. After PTFE-patch implantation with
      separately fixed overlapping border, 1 (11%) of 9 patients had a recurrent
      hernia. In the group with the PTFE-cone implantation, 1 (9%) of 11 patients
      developed a recurrence. Meanwhile, another 20 CDH patients received implantation
      of a cone-shaped patch, and no further recurrence occurred up to now. With the
      additional space (20 mL) provided by the cone-shaped patch, the closure of the
      abdomen was easier, and the fundus had intraoperatively a physiological position.
      CONCLUSION: This optimized patch implantation technique in large diaphragmatic
      defects offers considerable advantages especially regarding recurrence of the
      hernia and closure of the abdomen, which are currently the most challenging
      surgical problems. 1. The cone-shaped 3-dimensional patch increases abdominal
      capacity. 2. Redundant chest capacity is reduced, and the reconstructed diaphragm
      shows a physiological shape. 3. The dome of the patch allows a physiological
      position of the gastric fundus and a normal Hiss angle, thus preventing
      gastroesophageal reflux. 4. Additional safety of the implantation is achieved by
      separate fixation of the overlapping border of the cone, preventing recurrence.

PMID- 16291157
TI  - Thoracoscopic diaphragmatic eventration repair in children: about 10 cases.
AB  - BACKGROUND AND AIM: Recent reports in literature have emphasized the clinical
      perception of reduced pain, postoperative morbidity, and dysfunction associated
      with thoracoscopic approach compared with standard thoracotomy. The authors
      describe a thoracoscopic approach and technical details for diaphragmatic
      eventration repair in children. PATIENTS AND METHODS: Ten patients, 4 girls and 6
      boys, 1 teenager (14 years old) and 9 children (age range, 6-41 months; average,
      17 months), were operated for a diaphragmatic eventration in 3 different
      pediatric surgery teams, according to the same technique. Symptoms were recurrent
      infection (7 cases), dyspnea on exertion (2 cases), and a rib deformity (1 case).
      An elective thoracoscopy was performed, patient in a lateral decubitus. A low
      carbon dioxide insufflation allowed a lung collapse. Reduction of the eventration
      was made progressively when folding and plicating the diaphragm. Plication of the
      diaphragm was done with an interrupted suture (6 cases) or a running suture (4
      cases). The procedure finished either with an exsufflation (4 cases) or a drain
      (6 cases). RESULTS: A conversion was necessary in 2 cases: 1 insufflation was not
      tolerated and 1 diaphragm, higher than the fifth space, reduced too much the
      operative field. Patients recovered between 2 and 4 days. Dyspnea disappeared
      immediately. Mean follow-up of 16 months could assess the clinical improvement in
      every patient. DISCUSSION: Thoracoscopic conditions are quite different between a
      diaphragmatic hernia repair previously reported and an eventration. Concerning
      diaphragmatic hernias, reduction is easy, giving a large operative space for
      suturing the diaphragm. Concerning diaphragmatic eventrations, the lack of space
      remains important at the beginning of the procedure despite the insufflation into
      the pleural cavity. The operative ports must be high enough in the chest to allow
      a good mobility of the instruments. Chest drainage seems to be unnecessary.
      CONCLUSION: Diaphragmatic eventration repair by thoracoscopy is feasible, safe,
      and efficient in children. Above all, it avoids a thoracotomy. It improves the
      immediate postoperative results with a good respiratory function.

PMID- 16291156
TI  - Nitrovasodilator responses in pulmonary arterioles from rats with nitrofen
      induced congenital diaphragmatic hernia.
AB  - BACKGROUND/PURPOSE: Many infants with congenital diaphragmatic hernias (CDHs)
      experience persistent pulmonary hypertension that is refractory to treatment with
      inhaled nitric oxide (NO). We have examined the responses of isolated pulmonary
      arterioles from prenatal and postnatal rats with and without nitrofen (2,4
      dichlorophenyl-p-nitrophenyl ether)-induced CDH to a variety of activators of the
      NO-cyclic guanosine monophosphate (cGMP) pathway. METHODS: Right-sided CDH was
      induced in fetal rats by feeding nitrofen to pregnant rats on day 12 of
      gestation. Control rats were fed olive oil (vehicle). Third-generation pulmonary
      arterioles were isolated from the right lung of prenatal rats at term and from
      newborn rats within 8 hours after birth. Responses to increasing concentrations
      of sodium nitroprusside (SNP), atrial natriuretic peptide, or 8-bromo-cGMP were
      measured in pulmonary arterioles from control rats and from rats with nitrofen
      induced CDH. Postnatal responses to 8-bromo-cGMP were also recorded in the
      presence of zaprinast, a type V phosphodiesterase inhibitor. RESULTS: Pulmonary
      arterioles from prenatal rats did not dilate in response to SNP, atrial
      natriuretic peptide, or 8-bromo-cGMP. Vasodilatory responses of postnatal
      pulmonary arterioles from control rats to SNP and 8-bromo-cGMP were significantly
      greater than for arterioles from rats with CDH. Zaprinast pretreatment resulted
      in similar responses for postnatal CDH and control arterioles to 8-bromo-cGMP.
      CONCLUSIONS: Postnatal pulmonary arterioles from CDH rats exhibit altered
      nitrovasodilator responsiveness, which may be due to rapid degradation of cGMP.

PMID- 16291158
TI  - Estrogen receptor expression in anomalous arrangement of the pancreaticobiliary
      duct.
AB  - BACKGROUND/PURPOSE: Anomalous arrangement of the pancreaticobiliary duct (AAPBD)
      is a malformation of the bile and pancreatic ducts which is commonly associated
      with congenital biliary dilatation and predominantly occurs in girls. Estrogen
      receptor (ER) is reported to modulate cholangiocyte proliferation and play a role
      in tumorigenesis of estrogen-dependent malignancies. The present study
      investigated the presence of ER in the gallbladder of patients with AAPBD to
      elucidate whether ER expression is correlated with sexual specificity and biliary
      histology. METHODS: Specimens comprised samples of 29 gallbladders from patients
      with AAPBD (21 girls and 8 boys; mean age at surgery, 5.3 years). Medical records
      were retrospectively reviewed, and sex, age, radiographic parameters, and
      laboratory data were collected for this study. Immunohistochemistry was performed
      using anti-ER and anti-MIB-1 antibodies, and MIB-1 score was calculated for
      evaluation of cell proliferation. RESULTS: ER expression was observed in both the
      nuclei and cytoplasm of gallbladder epithelium in 12 of 29 specimens. No
      difference in background characteristics were noted between ER-positive and ER
      negative groups. Mucosal hyperplasia was found in 17 specimens. ER-positive cases
      were significantly more common in AAPBD with mucosal hyperplasia than without (P
      <0.03). MIB-1 score did not differ significantly between ER-positive and ER
      negative groups. CONCLUSIONS: ER expression seems to be related to hyperplastic
      mucosa of the gallbladder in AAPBD. ER might play a role in the proliferation of
      gallbladder epithelium.

PMID- 16291159
TI  - Connective tissue growth factor expression is increased in biliary epithelial
      cells in biliary atresia.
AB  - BACKGROUND/PURPOSE: Connective tissue growth factor (CTGF) has been implicated in
      the pathogenesis of hepatic fibrosis and is elevated in the serum of children
      with biliary atresia (BA). The objective of this study was to evaluate hepatic
      CTGF messenger RNA (mRNA) expression and its relationship to hepatic histology in
      children with BA. METHODS: Connective tissue growth factor mRNA expression was
      evaluated by in situ hybridization in 26 liver biopsies from 11 patients with BA,
      11 with other diseases, and 4 autopsy controls. Serial sections were
      immunostained with cell-specific markers to characterize the cells expressing
      CTGF. Biopsies were scored for CTGF expression (0-4) and inflammation and
      fibrosis (1-4). RESULTS: High levels of CTGF expression were observed in 9 of 11
      BA with localization to biliary epithelial cells and vascular endothelial cells.
      Connective tissue growth factor mRNA expression was correlated with fibrosis in
      BA and all livers. In the 11 patients with other liver diseases, 7 had CTGF
      expression limited to hepatic stellate cells and vascular endothelial cells. None
      of the 4 livers in children without liver disease had significant levels of CTGF.
      CONCLUSIONS: In BA livers, novel biliary epithelia CTGF mRNA expression is high
      and correlates with severity of fibrosis. These data support a role for biliary
      epithelial cell signaling in fibrogenesis.

PMID- 16291160
TI  - A randomized controlled trial of elective preterm delivery of fetuses with
      gastroschisis.
AB  - BACKGROUND: Elective preterm delivery of the fetus with gastroschisis may help to
      limit injury to the extruded fetal gut and thus promote faster recovery of
      neonatal gut function and earlier hospital discharge. This hypothesis has not
      previously been tested in a prospective randomized controlled trial. METHODS:
      Between May 1995 and September 1999, all women referred to a single tertiary
      center before 34 weeks' gestation with a sonographically diagnosed fetal
      gastroschisis were invited to participate in a randomized controlled trial.
      Eligible patients were randomized to elective delivery at 36 weeks or to await
      the onset of spontaneous labor. The method of delivery was not prescribed by the
      trial. Primary outcome measures in the neonate were the time taken to tolerate
      full enteral feeding (150 mL/kg per day) and duration of hospital stay. RESULTS:
      Of 44 eligible women, 42 were randomized, 21 to elective delivery and 21 to await
      spontaneous labor. There were 20 liveborn infants in each group. Four babies in
      the elective group and 4 in the spontaneous group delivered before 36 weeks'
      gestation but were included in the analysis on an intention-to-treat basis. Mean
      gestational age at delivery was 35.8 weeks in the elective group and 36.7 weeks
      in the spontaneous group. Primary closure of the gastroschisis was achieved in a
      similar proportion (80%-85%) of infants in both groups. Two babies in the
      elective group died from short gut complications. In the survivors, there was a
      trend in favor of a shorter median time to achieve full enteral feeding (30.5 vs
      37.5 days) and a shorter median duration of hospital stay (47.5 vs 53 days) in
      the elective group, but this was not statistically significant. These findings
      remained unaltered when the data were reanalyzed after (a) excluding infants with
      intestinal atresia or (b) excluding infants born before 36 weeks' gestation.
      CONCLUSIONS: Although limited by the small number of patients, this randomized
      controlled trial demonstrates no significant benefit from elective preterm
      delivery of fetuses with gastroschisis.

PMID- 16291161
TI  - Myoelectrical activity of the stomach after surgical correction of esophageal
      atresia.
AB  - AIM: The aim of this study was to investigate the motor activity in the stomach
      of infants with repaired esophageal atresia (EA). METHOD: Gastric myoelectrical
      activity was investigated by cutaneous electrogastrography in 15 infants after
      the surgical correction of EA. Ten infants with no gastrointestinal upset served
      as controls. Studies were done before and after a milk feed. The pH of the lower
      esophagus was measured for 24 hours to assess the gastroesophageal reflux (GER)
      in the infants with repaired EA. RESULTS: After feeding, a significant increase
      in bradygastria and decrease in tachygastria were observed as compared with the
      preprandial period. Compared with healthy infants, the electrogram showed
      pathological patterns in 73.3% (11/15) of EA patients. Twelve of 15 EA patients
      showed some clinical sign of GER, and 60% of the EA patients proved to be GER
      positive on esophageal pH monitoring. There was no difference in the distribution
      of gastric myoelectrical waves between the GER-positive and GER-negative EA
      patients either before or after meal. CONCLUSION: Cutaneous electrogastrography
      is a noninvasive, harmless method for obtaining indirect information about the
      motor function of the stomach. The abnormal changes in physiological gastric
      myoelectrical activity in EA patients can serve as markers of disturbed
      neuromuscular function and can play a role in the pathogenesis of feeding
      disturbances after operative correction of EA. Gastroesophageal reflux, which
      often occurs after surgical repair of EA, seems to be connected not only with
      disordered gastric myoelectric activity, but also probably with other factors
      such as artificially straightened esophagogastric angle or brachyesophagus.

PMID- 16291162
TI  - Effectiveness of alimemazine in controlling retching after Nissen fundoplication.
AB  - BACKGROUND: Retching, an early component of the emetic reflex, is a common and
      distressing symptom in children after Nissen fundoplication. Alimemazine
      (trimeprazine, Vallergan; Castlemead, Herts, UK) is a phenothiazine derivative
      histamine(1) antagonist, which anecdotally relieves the retching symptoms.
      MATERIAL AND METHODS: A prospective, double-blind, randomized, crossover, placebo
      controlled study of 15 neurologically impaired children with retching after
      Nissen fundoplication over a period of 1 year (December 2002-December 2003).
      Patients were randomly allocated to receive 1 week each of alimemazine and
      placebo with crossover. A diary was maintained of retching episodes 1 week
      before, during, and 1 week after the trial. Dosage of alimemazine used was 0.25
      mg/kg 3 times a day (maximum, 2.5 mg per dose). Statistical analysis was done
      using a paired Student's t test, where P value of less than .05 was considered
      significant. Results are presented as mean +/- SD. RESULTS: Twelve parents
      completed the diaries (9 open, 3 laparoscopic Nissen fundoplication). Median age
      of the child was 36 months (8-180 months), median duration of retching was 4.5
      months (1-52 months), and mean number of retching episodes per week was 60 +/-
      29.40. Mean number of retching episodes with alimemazine was 10.42 +/- 9.48 vs
      47.67 +/- 27.79 with a placebo (P < .0001). No adverse effects were reported in
      those cases that completed the study. CONCLUSION: At low dose, alimemazine
      (Vallergan) is a safe and effective drug in the management of retching after
      Nissen fundoplication.

PMID- 16291163
TI  - Timing, route, and dose of administration of heparin-binding epidermal growth
      factor-like growth factor in protection against intestinal ischemia-reperfusion
      injury.
AB  - PURPOSE: We have previously demonstrated that heparin-binding epidermal growth
      factor-like growth factor (HB-EGF) is an intestinal cytoprotective agent. The
      current study examined whether HB-EGF is effective as salvage therapy as well as
      prophylactic therapy for intestinal ischemia-reperfusion (I/R) injury, whether
      intravenous administration is as effective as intraluminal administration, and
      whether increased benefits are seen with increasing dose. METHODS: Total midgut
      I/R injury in rats was achieved by occlusion of a first-order branch of the
      superior mesenteric artery for 60 minutes, followed by reperfusion for 6 hours.
      Rats were treated with HB-EGF 5 minutes before ischemia, halfway through the
      ischemic event, or 5 minutes after ischemia. Route of administration was tested
      by administering HB-EGF either intraluminally or intravenously. Seven different
      doses of HB-EGF were tested. RESULTS: Heparin-binding, EGF-like growth factor
      protected the intestine from injury when administered before injury and was also
      effective when administered during ischemia or even after injury. Intraluminal
      administration of HB-EGF was superior to intravenous administration. Increasing
      doses of HB-EGF resulted in a greater cytoprotective effect. CONCLUSION: These
      data demonstrate that HB-EGF acts as an effective intestinal cytoprotective agent
      when administered intraluminally not only before injury, but also during injury
      and, most importantly, even after intestinal injury has already occurred. These
      findings support a basis for the prophylactic use of intraluminal HB-EGF in high
      risk patients, as well as for the administration of HB-EGF to salvage patients in
      whom an intestinal insult has already occurred.

PMID- 16291164
TI  - Effects of surgical repair of congenital diaphragmatic hernia on cerebral
      hemodynamics evaluated by near-infrared spectroscopy.
AB  - BACKGROUND: Cardiorespiratory stabilization is recommended before surgical repair
      of congenital diaphragmatic hernia (CDH) because surgery may induce a transitory
      deterioration of chest compliance and gas exchange. It is not known if surgical
      intervention can affect cerebral circulation and oxygenation. AIM: The aim of the
      study was to assess noninvasively, by near-infrared spectroscopy, the possible
      changes in cerebral hemodynamics and oxygenation associated with surgical repair
      of CDH. SUBJECTS: Twenty-five newborns with severe CDH (birth weight, 3057 +/-
      354 g; gestational age, 37.8 +/- 1.8 weeks; male/female newborns, 15/10;
      left/right CDH, 19/6) were sedated, paralyzed, and mechanically ventilated by
      conventional gentle ventilation and surgically corrected at a median age of 2.7
      days (min-max, 2-14 days) after cardiorespiratory stabilization. METHODS: Heart
      rate (HR [beats per minute]), preductal transcutaneous oxygen saturation (tcSaO2
      [%]), carbon dioxide tension (tcPCO2 [Torr]), and mean arterial blood pressure
      (mm Hg) were continuously monitored. Inspired fractional oxygen concentration
      (FIO2) was adjusted to maintain and preductal tcSaO2 of greater than 80%, whereas
      the ventilator's settings were kept unchanged throughout the surgical procedure.
      Cerebral hemodynamics was assessed by near-infrared spectroscopy (NIRO 300,
      Hamamatsu Photonics, Japan), recording continuously and noninvasively the
      relative changes in concentration of oxygenated (DeltaO2Hb [micromol/L]),
      deoxygenated (DeltaHHb [micromol/L]), and total (DeltatHb [micromol/L])
      hemoglobin; the tissue oxygenation index (TOI [%]) was also calculated (TOI =
      O2Hb/O2Hb + HHb). Total hemoglobin concentration is considered to be
      representative of cerebral blood volume. Arterial blood gases were also measured
      at the beginning (T1) and at the end of surgery (T2). For all measurements,
      results at T1 and at T2, as well as the differences between T1 and T2, have been
      expressed as means or medians and SDs or 95% confidence intervals or ranges. The
      differences between T1 and T2 were considered statistically significant for a P
      value of less than .05 by the Student t test for paired values. RESULTS: At T1,
      mean tcSaO2% was 94.1 % (SD, 4.6) with a FIO2 of 0.25 (SD, 0.1); at T2, to obtain
      similar values of tcSaO2 (93.4%; SD, 4.4), it was necessary to increase the FIO2
      to 0.37 (SD, 0.14; P < .001). Mean HR at T1 was 149.5 beats per minute (SD, 9.1)
      and increased significantly (P < .05) at T2 (165.2 beats per minute; SD, 14.2).
      Mean arterial blood pressure was 54.7 mm Hg (SD, 7.7) at T1 and did not change
      appreciably at T2 (55.6 mm Hg; SD, 8.1). Moreover, tcPCO2 did not change
      significantly during the procedure (mean tcPCO2 = 49.9 Torr [SD, 12.8] at T1 and
      57.3 mm Hg [SD, 17.9] at T2). O2Hb and tHb decreased (P < .001 and <.005) and HHb
      increased (P < .05) significantly during the surgical procedure (mean Delta [SD]:
      DeltaO2Hb= -10.9 micromol/L [9.7], DeltatHb = -7.5 micromol/L [11.7], and
      DeltaHHb = -3.5 micromol/L [6.8]). Mean TOI was 70% at T1 (normal values >60%)
      and decreased significantly at T2 (mean DeltaTOI = -6.1% [SD, 10.6]). In all
      infants, the greatest changes occurred when the viscera were positioned into the
      abdomen. CONCLUSIONS: Notwithstanding the initial cardiorespiratory
      stabilization, surgical repair of CDH was associated with a rise in HR and oxygen
      requirement and a drop in cerebral tHb and O2Hb, suggesting a reduction in
      cerebral blood volume and oxygenation. These events were probably due to the
      combined effects of an increase in right to left shunting (as indicated by the
      increased oxygen requirement) and a decrease in venous return (possibly due to
      compression of the inferior vena cava by the viscera positioned into the
      abdomen). These preliminary results reinforce the importance of achieving a good
      cardiorespiratory stability before undertaking surgical correction of CDH to
      minimize the possible interference of the procedure with cerebral circulation and
      oxygenation.

PMID- 16291165
TI  - Surgical treatment and prognosis of chronic intestinal pseudo-obstruction in
      children.
AB  - BACKGROUND/PURPOSE: Chronic intestinal pseudo-obstruction (CIPO) is characterized
      by symptoms of intestinal obstruction in the absence mechanical blockage. The
      main objectives in the treatment of CIPO include maintenance of adequate
      nutrition and restoration of intestinal propulsion. Our aim was to document the
      results of surgical treatment and the long-term results of CIPO in children.
      METHODS: The cases of 22 children (14 boys and 8 girls) who underwent surgical
      treatment for CIPO between January 1985 and April 2004 were reviewed. Patients at
      initial presentation ranged in age from 1 day to 11 years (median, 3.5 months).
      The diagnosis of CIPO was based on clinical signs and symptoms, coupled with
      radiological and histological findings. Patients' outcomes fell into 4 groups,
      according to evaluations of oral intake, weight gain, and parenteral nutrition:
      expired, poor, fair, or good. RESULTS: In 3 cases of localized disease, both
      total gastrectomy and total colectomy were performed in combination. Of 19 cases
      of generalized disease, 7 patients received enterostomy and/or intestinal biopsy,
      followed by total colectomy and Duhamel operation. Another 4 of those 19 patients
      underwent enterostomy repair, and 2 were treated by small bowel resection. In
      terms of outcome, 5 patients were expired, 5 were classified as poor, 4 were
      described as fair, and 8 had outcomes that fell into the good category. In
      expired patients, the causes of death were either line-associated sepsis or
      hypovolemic shock associated with intestinal obstruction. The only cases in which
      the outcomes were good were cases in which there was evidence of intestinal
      neuronal dysplasias. CONCLUSION: We suggest that operative treatment should be
      considered, because of a high probability of both difficult diagnosis and
      intractable symptoms, which are unresponsive to medical therapy.

PMID- 16291166
TI  - Evaluation of Hox11L1 in the fmc/fmc rat model of chronic intestinal pseudo
      obstruction.
AB  - BACKGROUND/PURPOSE: The spontaneous rat mutation, familial megacecum and colon
      (fmc), is responsible for an autosomal recessive phenotype similar to intestinal
      pseudo-obstruction observed in Hox11L1-/- mice. We hypothesized that fmc is a
      mutant allele of the rat Hox11L1 gene and tested this hypothesis by direct
      sequencing. METHODS: DNA was extracted from fmc/fmc rats and wild-type
      littermates. All exons, introns, and DNA 5' to the transcriptional start site of
      rat Hox11L1 were directly sequenced, and data from the mutant and wild-type
      animals were compared with each other and corresponding genomic data from humans
      and mice. RESULTS: Alignment of sequences obtained from rat, human, and mouse
      indicates that putative regulatory elements of the Hox11L1 gene are conserved in
      rat, mice, and humans. No mutations were identified in the Hox11L1 allele of
      fmc/fmc rats. CONCLUSIONS: Despite the phenotypic similarities between fmc/fmc
      rats and Hox11L1-/- mice, fmc does not appear to be a mutant allele of the
      Hox11L1 gene.

PMID- 16291167
TI  - Stooling patterns and colonic motility after transanal one-stage pull-through
      operation for Hirschsprung's disease in children.
AB  - BACKGROUND: The transanal one-stage endorectal pull-through operation for
      Hirschsprung's disease is relatively new and makes assessment of the functional
      outcome and colonic motility difficult. The aim of this study was to evaluate the
      stooling patterns and colonic motility after a one-stage transanal pull-through
      operation for Hirschsprung's disease in children. METHODS: Twenty-two children
      who underwent a one-stage transanal pull-through operation for Hirschsprung's
      disease were followed up for at least 6 months. The children (17 boys and 5
      girls) were from 12 months to 13 years of age (mean age, 4 years). All patients
      had an aganglionic segment confined to the rectosigmoid area (confirmed by
      preoperative barium enema and postoperative histology). Clinical outcome was
      assessed by interviews and questionnaires, and children were divided into
      symptomatic and nonsymptomatic groups. Contrast barium enema and defecography and
      determination of total and segmental colonic transit time (using radio-opaque
      markers) were performed on all 22 children. RESULTS: The stooling patterns were
      considered satisfactory in 17 children. Of all the children, the mean stool times
      were 1 to 2 per day and only 2 were 8 to 10 per day; postoperative soiling was
      found in 4, constipation was observed in 2, and Hirschsprung-associated
      enterocolitis in 1. There was no incontinence, cuff infection, anastomotic leak,
      or mortality noted. Barium enema showed that the dilated and spastic colonic
      segment disappeared in all 22 children. The dilated sigmoid loops decreased in 17
      (2 symptomatic, 15 nonsymptomatic) and disappeared in 5 (4 symptomatic, 1
      nonsymptomatic). There was a significant difference between the decreasing and
      disappearing loop group in regard to stooling disorders (P < .05). Postoperative
      defecography showed that the anorectal angle of all children was open, fixed, and
      significantly larger than that of the preoperative and control groups (123.3
      degrees +/- 15.1 degrees vs 84.7 degrees +/- 8.3 degrees vs 79.0 degrees +/- 11.6
      degrees, P < .01) and larger in the symptomatic group when compared with the
      nonsymptomatic group (135.6 degrees +/- 15.9 degrees vs 111.0 degrees +/- 14.3
      degrees, P < .05). Postoperatively, the total gastrointestinal transit time, left
      colonic transit time, and rectosigmoid colonic transit time of all the children
      were shorter than preoperatively (26.8 +/- 8.2 vs >188 hours, P < .01; 6.3 +/-
      4.1 vs >60 hours, P < .01; 11.8 +/- 4.4 vs >120 hours, P < .01) and similar to
      controls. The total gastrointestinal transit time and rectosigmoid colonic
      transit time of the symptomatic group were significantly shorter than the
      nonsymptomatic group (25.2 +/- 5.6 vs 28.1 +/- 10.1 hours, P < .05; 12.2 +/- 6.7
      vs 9.8 +/- 4.0 hours, P < .05). CONCLUSIONS: The stooling pattern and colonic
      motility are satisfactory in most children after the one-stage transanal pull
      through operation for Hirschsprung's disease. Normalization of colon appearance
      and total and segmental colonic transit time are signs of recovery of colonic
      motility. Stooling disorders were noted in a few cases and may be related to
      decrease or disappearance of the sigmoid loop, dysfunction of the
      "neorectosigmoid", an open and fixed anorectal angle, and ischemia of the pull
      through segment.

PMID- 16291168
TI  - Stapled restorative proctocolectomy in children with refractory ulcerative
      colitis.
AB  - OBJECTIVE: The aim of this study was to review the results after stapled
      restorative proctocolectomy among children with refractory ulcerative colitis.
      PATIENTS AND METHODS: Clinical records of 16 consecutive children with refractory
      ulcerative pancolitis undergoing colectomy and stapled straight ileoanal
      anastomosis at a median age of 8.3 years (range, 3.1-14.9 years) were reviewed.
      Periodical clinical examinations and endoscopies with biopsies above (terminal
      ileum) and below (columnar cuff) the anastomosis were carried out during follow
      up. Median follow-up after bowel restoration lasted 5.3 years (range, 1.2-9.6
      years). RESULTS: Two major complications occurred (12.5%), 1 episode of sepsis
      treated conservatively and 1 bowel perforation proximal to the anastomosis
      treated with a temporary diverting ileostomy. All the anastomoses were functional
      at the end of the study. The columnar cuff averaged 2.6 cm in length and
      presented signs of persistent inflammation (cuffitis) in 94% of children.
      Inflammation responded poorly to any medical treatment but was symptomatic in 1
      case only. Ileal inflammation was detected endoscopically in 31% of patients and
      histologically in 62.5%. No case of dysplasia or cancer was recorded. At final
      follow-up, children had an average of 7.1 +/- 3.1 bowel movements per day; full
      daytime and nighttime continence were achieved in 87.5% and 62.5% of cases,
      respectively. A severe inflammation of the columnar cuff was associated with an
      increased risk of nighttime incontinence. CONCLUSIONS: Stapled ileoanal
      anastomosis in children with pancolitis is associated with low morbidity.
      Refractory cuffitis persists in almost all patients but is mostly asymptomatic,
      although it could be associated with nighttime incontinence.

PMID- 16291169
TI  - The value of open surgical approaches for aspirated pen caps.
AB  - PURPOSE: The aim of this study was to present the therapeutic approach of
      aspirated pen cap foreign bodies, with emphasis on the importance of open
      surgical intervention. METHODS: The records of patients who underwent
      bronchoscopy and bronchoscopy and surgical therapy for pen cap foreign bodies
      between January 1997 and June 2003 were reviewed retrospectively. Diagnosis was
      made based on history, physical examination, radiological methods, and
      bronchoscopy. Age, sex, symptoms, radiological methods, surgical procedure,
      complications, and outcomes were recorded. RESULTS: A total of 24 bronchoscopies
      were performed on 19 patients (10 boys, 9 girls) with a median age of 11 years
      (range, 8-15 years). Pen caps were localized in the right bronchial tree in 14
      cases (74%). Pen caps were extracted successfully by forceps during bronchoscopy
      in 9 patients. Of the remaining 10 patients, 5 underwent bronchoscopy and
      tracheostomy and 5 patients underwent thoracotomy and bronchotomy. Significant
      complications were observed in 2 patients (10.53%) (severe bronchospasm in one
      and pneumothorax and subglottic edema in another). CONCLUSIONS: Pen caps
      aspiration is a challenging problem because of the difficulties during extraction
      and higher morbidity compared with other foreign body aspirations. In such cases
      in which classic bronchoscopy failed and/or pen caps could not be removed via
      vocal cords, open surgical approaches, either bronchoscopy and tracheostomy or
      thoracotomy and bronchotomy, may be an alternative procedure of choice.

PMID- 16291170
TI  - A new fistulectomy method for the second pharyngeal arch remnants.
AB  - PURPOSE: We present a new fistulectomy method for the second pharyngeal arch
      remnants. MATERIALS AND METHODS: Between 1991 and 2003, 4 patients have been
      treated with a new fistulectomy method. SURGICAL PROCEDURE: Under general
      anesthesia with nasotracheal intubation, the neck and mouth are prepared as one
      operative field. A nylon thread is inserted into the cervical opening. On the
      oral site of the nylon thread, a small gauze ball is tied and gently pulled from
      the neck site. At both opening sites of the fistula, a very small incision around
      the nylon thread is performed. Using the nylon thread as a guide, a fistulectomy
      is carried out. RESULTS: In all 4 patients, no complications have occurred during
      and after the fistulectomy. No recurrences were seen during 15 months to 9 years.
      CONCLUSIONS: This is a simple and useful procedure for the treatment of second
      pharyngeal arch remnants. It produces an excellent cosmetic result compared with
      the standard method because only one small incision is necessary.

PMID- 16291171
TI  - Cardiopulmonary resuscitation in patients with a Nuss bar--a case report and
      review of the literature.
AB  - Pectus excavatum (PE) is a common chest wall deformity that may produce a variety
      of physiological and psychological effects in children and adolescents. In
      addition, some of these patients have associated cardiac diseases (ie, mitral
      valve prolapse and Marfan syndrome). Recently, a minimally invasive surgical
      repair of PE that requires sternal bar placement has become increasingly frequent
      to enhance patients' cardiopulmonary functioning as well as their self-esteem.
      However, despite this innovative technique, it is possible for such patients to
      have a cardiac arrest while their sternal bar is in place. Whether the presence
      of a metal bar on the underside of their sternum may hinder resuscitative chest
      compressions (cardiopulmonary resuscitation) is an issue that concerns us, our
      patients, and their families; the answer requires further investigation. We
      present a 21-year-old man with PE who underwent a minimally invasive pectus
      repair but had a fatal cardiac event before bar removal. Paramedics conducting
      cardiopulmonary resuscitation on the patient later reported that they were unable
      to deliver effective cardiac compressions and that the sternal bar may have
      contributed to this.

PMID- 16291172
TI  - Chronic abdominal pain secondary to a mucous cystadenoma of the appendix in a 10
      year-old boy.
AB  - Mucocele of the appendix is a thin-walled dilated appendix filled with mucus. It
      occurs secondary to chronic obstruction of the appendiceal lumen because of a
      range of pathologies. Cystadenomas in children are exceedingly rare and most
      frequently of ovarian origin. A mucous cystadenoma of the appendix in a 10-year
      old boy with chronic abdominal pain is presented.

PMID- 16291173
TI  - Torsion of the epididymis.
AB  - Anomalies of the epididymis are most commonly associated with an undescended
      testis but also found occasionally in a normally descended testis. Our 11-year
      old patient presented with an acute scrotum and Doppler ultrasound that suggested
      epididymitis. Painful symptoms required scrotal exploration with the finding of a
      torsion and infarction of the epididymis. The etiology of the torsion was an
      abnormal attachment of the epididymis to the testis. Torsion of the epididymis
      has not previously been reported.

PMID- 16291174
TI  - Advanced-stage gastrointestinal stromal tumor treated with imatinib in a 12-year
      old girl with a unique mutation of PDGFRA.
AB  - A 12-year-old girl presented with a large abdominal tumor. At surgery, a huge
      pedunculated extraluminal tumor was found arising from the greater curvature of
      the stomach and invading the surrounding structures, and there were also a
      submucosal tumor measuring 5 x 4 x 4 cm and multiple intramural nodules beside
      the main tumor. These lesions, which were removed with 1.0-cm surgical margins,
      were immunohistochemically positive for c-kit (CD117) and CD34. A diagnosis of
      gastrointestinal stromal tumor (GIST) was made. The huge size of the tumor (3.6
      kg in weight and 36 x 25 x 25 cm in diameter), the invasion of the surrounding
      structures, and the increased mitotic figures indicated the GIST had malignant
      potential. Sequence analysis of the polymerase chain reaction product of RNAs
      from the tumor cells revealed a novel platelet-derived growth factor receptor
      alpha (PDGFRA) mutation, which would exhibit biologic consequences similar to
      those of the c-kit mutation. The patient underwent a 3-month course of imatinib
      mesylate as adjuvant chemotherapy because of the possible risk for tumor
      recurrence. She is now doing well without any evidence of recurrence or
      metastasis 25 months after the surgery. Only 9 cases of GIST have been reported
      in children, and a review of those cases revealed GISTs in children would be
      associated with a better prognosis than in adults and that one third of pediatric
      GISTs presented with intestinal obstruction in the newborn period.

PMID- 16291175
TI  - Pyloric stenosis in in vitro fertilized triplets--is it a coincidence?
AB  - Infantile hypertrophic pyloric stenosis was previously reported in multiple
      births, but there were only 3 triplets in the literature and all were naturally
      conceived. Assisted reproductive technologies, such as in vitro fertilization,
      are accused for increasing the risk for some anomalies in children. Triplets of
      in vitro fertilization, all of whom were operated on because of pyloric stenosis,
      are presented.

PMID- 16291176
TI  - Necrotizing fasciitis: a rare complication of neonatal necrotizing enterocolitis.
AB  - Necrotizing fasciitis is a rapidly spreading soft tissue infection affecting the
      subcutaneous tissue and underlying fascial layers. Although this infection
      pattern is commonly seen in adults, it is rarely seen in the neonatal population.
      Herein, we describe a patient who developed extensive necrotizing fasciitis of
      the abdominal wall after intestinal resection for necrotizing enterocolitis
      (NEC).

PMID- 16291177
TI  - Polytetrafluoroethylene patch repair of a saccular abdominal aortic aneurysm in a
      5-year-old boy.
AB  - A 5-year-old boy presented with acute abdominal pain and was subsequently found
      to have an abdominal aortic aneurysm. The aetiology remains obscure. Repair was
      accomplished with a PTFE patch and he remains well on follow up.

PMID- 16291178
TI  - Surgical management of a pancreaticopleural fistula in a child with chronic
      pancreatitis.
AB  - Chronic pancreatitis in children rarely results in the development of a
      recalcitrant pleural effusion, secondary to a connection between the pleural
      cavity and the pancreas. We describe such a case and the curative surgical
      therapy and include a brief discussion of the relevant medical literature as it
      pertains to this complication in the pediatric population.

PMID- 16291180
TI  - Glutathione (GSH) levels in necrotizing enterocolitis (NEC).

PMID- 16291181
TI  - Forecasting models to quantify three anthropogenic stresses on coral reefs from
      marine recreation: anchor damage, diver contact and copper emission from
      antifouling paint.
AB  - This research focuses on damage to coral reefs from three anthropogenic stresses:
      the dropping of anchors and their chains, human contact, and emission of copper
      from antifouling paints. Forecasting models are described that quantify
      degradation in terms of percentage of coral cover damaged/year or increasing
      levels of water toxicity/year. The models utilize a Monte Carlo simulation that
      applies a range of values or a probability distribution to each of the numerous
      uncertain variables. This model has the flexibility to adapt, and become more
      accurate, when users input assumptions specific to their diving sites. Given our
      specific assumptions for a frequently visited site, anchors and their chains
      forecast a distribution of coral reef cover damage with a mean of 7.11%+/-4.77%,
      diver contact forecast a distribution of coral reef cover damage with a mean of
      0.67%+/-0.38%, and antifouling paint forecast a distribution of copper level
      increase in the water with a mean of 0.037+/-0.014ppb. The results support
      recommendations for the implementation and sustained use of several specific
      marine recreation practices.

PMID- 16291182
TI  - Assessing cause and effect of multiple stressors on marine systems.
AB  - An operational framework is developed to serve as a guideline for investigating
      causal relationships between environmental stressors and effects on marine biota.
      Because of the complexity and variability of many marine systems, multiple lines
      of evidence are needed to understand relationships between stressors and effects
      on marine resources. Within this framework, a weight of evidence approach based
      on multiple lines of evidence are developed and applied in a sequential manner by
      (1) characterizing the study system which involves determining if target biota
      are impaired, assessment of food and habitat availability, and measuring
      contaminant levels in the environment, (2) assessing direct effects of
      contaminant exposure on target biota using biomarkers and assessing indirect
      effects of exposure using suites of bioindicators, and (3) applying standard
      causal criteria based on epidemiological principles and diagnostic health
      profiling techniques to assess potential causes. Use of multiple lines of
      evidence should also reduce the risk of false positives (Type I error or falsely
      concluding that there is a causal relationship when there is none) and false
      negatives (Type II error or falsely concluding there is not a causal relationship
      when there actually is). Understanding causal relationships and the mechanistic
      processes between environmental stressors and effects on biota is important in
      the effective management and restoration of impaired marine ecosystems.

PMID- 16291184
TI  - Toxic effects of copper on larval development of the barnacle Balanus amphitrite.
AB  - Experiments were conducted to assess the effects of copper on larval development
      in the barnacle Balanus amphitrite. In the first experiment, we compared the
      sensitivity of three naupliar stages to copper stress. Molting inhibition
      occurred at copper concentrations ranging from 32 microg l(-1) in nauplius II to
      128 g l(-1) in nauplius VI. EC50 for molting ranged from 97 microg l(-1) in
      nauplius II to 129 g l(-1) in nauplius VI. Decreased survival occurred at 128
      microg Cu l(-1) in all of the naupliar stages tested, with LC50 ranging from 145
      in nauplius II to 213 microg l(-1) in nauplius VI. In the second experiment, we
      examined effects of copper on the development from nauplius II to cyprid. The
      larvae reached cypris stage only in treatments of 16 microg Cu l(-1). Our study
      therefore showed that molting was a more sensitive endpoint than survival,
      nauplius II was the most sensitive naupliar stage, and that whole larval
      development assay was more sensitive than assays using a particular larval stage.
      The results were discussed with respect to the use of this species in toxicity
      tests.

PMID- 16291183
TI  - Polybrominated diphenyl ethers (PBDEs) and organochlorines in small cetaceans
      from Hong Kong waters: levels, profiles and distribution.
AB  - Polybrominated diphenyl ethers (PBDEs) and organochlorine compounds (OCs) were
      determined in the blubber, liver and kidney of Indo-Pacific humpback dolphins
      (Sousa chinensis) and finless porpoises (Neophocaena phocaenoides) stranded in
      Hong Kong coastal waters during 1995-2001. Among the organohalogen compounds
      analyzed, DDTs were the most dominant contaminants with concentrations ranging
      from 9.9 to 470 microg/g lipid wt. PBDEs in Hong Kong cetaceans, which are
      reported for the first time, were detected in all the samples with values ranging
      from 0.23 to 6.0 microg/g lipid wt., with a predominance of BDE-47. Results from
      this study suggest PBDEs should be classified as priority pollutants in Asia.
      Higher concentrations were found in humpback dolphins than in finless porpoises,
      and this was attributed mainly to differences in habitat. Elevated residues of
      PCBs and DDTs in some cetaceans suggest these species may be at risk.

PMID- 16291185
TI  - Field validation of antioxidant enzyme biomarkers in mussels (Perna viridis) and
      clams (Ruditapes philippinarum) transplanted in Hong Kong coastal waters.
AB  - Green-lipped mussels, Perna viridis, and Manila clams, Ruditapes philippinarum
      were sourced from "clean" sites in the Hong Kong region, depurated in a
      laboratory using uncontaminated filtered seawater for 8 days, and transplanted to
      a suspected gradient of chemically polluted sites in Hong Kong. After 14- and 28
      days of field exposure, several antioxidant parameters including glutathione S
      transferase (GST), catalase (CAT), glutathione peroxidase (GPx), and glutathione
      (GSH) were quantified in gill and hepatopancreas tissues. Whole body tissue
      concentrations of polycyclic aromatic hydrocarbons (PAHs), petroleum hydrocarbons
      (PHCs), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCs) were
      determined in pooled site samples. Chemical analyses indicated that: (a) clams
      had higher levels of PAHs, PHCs, DDTs and PCBs, whereas mussels had higher
      hexachlorocyclohexane (HCHs) and there was no difference between species for
      dieldrin and remaining OCs; (b) Kat O should not be continued as a "clean"
      reference site for Hong Kong, because of the levels of contaminants measured and
      (c) PAH concentrations in the current survey were similar to those previously
      measured. Toxicological conclusions were: (a) antioxidant responses were
      different between species; (b) CAT and GST have highest utility in clams for
      field use in Hong Kong, whereas CAT in both gill and hepatopancreas tissue showed
      most potential in mussels; (c) significant induction of antioxidant responses
      over day 0 (excluding GPx in both tissues, and GST in mussel hepatic tissue); (d)
      groups of contaminants do not consistently induce antioxidant responses and (e)
      organochlorines and PCBs correlated significantly with CAT and GST in clam
      hepatopancreas and with CAT in mussel gill and hepatic tissue. Multivariate
      statistical techniques indicated little relationship between the site patterns
      for antioxidant responses and the contaminant gradients identified in body burden
      analysis.

PMID- 16291186
TI  - Effects of 17beta-estradiol on the reproduction of Java-medaka (Oryzias
      javanicus), a new test fish species.
AB  - 17beta-estradiol (E2) is a female hormone which is known to be one of the
      strongest estrogenic chemicals in the environment. The present study investigated
      the effects of E2 on the reproduction of the estuarine fish, Java-medaka (Oryzias
      javanicus). Starting from the embryonic stages, Java-medaka was exposed for 6
      months to 9.5, 16, 68, 159 and 243 ng/l of E2. The fecundity of Java-medaka
      exposed to E2 levels >16 ng/l was significantly lower than that of the control.
      The appearance of secondary sexual characteristics seemed to be inhibited by
      exposure to 159 and 243 ng/l E2. Vitellogenin concentrations in the liver of male
      fish exposed to 68, 159 and 243 ng/l were significantly higher than that of the
      control. Thirty-three and sixty percent of male fishes exposed to 159 and 243
      ng/l, respectively, had testis-ova. These results suggest that reproduction in
      the Java-medaka, especially the male fish, could be affected by exposure to E2
      concentrations greater than 16 ng/l.

PMID- 16291187
TI  - Photosynthetic responses to Cu2+ exposure are independent of light acclimation
      and uncoupled from growth inhibition in Fucus serratus (Phaeophyceae).
AB  - We have studied the effect of light acclimation on photosynthetic responses and
      growth during Cu2+ exposure (0-0.84 microM) in the brown seaweed Fucus serratus.
      Measurements of chlorophyll fluorescence parameters showed that Cu2+ exposure
      amplified ETR, reduced the chlorophyll content at the cellular level and that
      there was no effect of light adaptation on the Cu2+ resistance of the algae. In
      contrast to the inhibitory effects of Cu2+ on chlorophyll fluorescence, O2
      evolution and the total content of chlorophyll and carotenoid of the algae was
      unaffected by Cu2+. We conclude that photoinhibition and perhaps pigment
      degradation in the meristoderm was compensated for by cells deeper in the thallus
      with the result that the overall photosynthetic fitness of the algae was
      maintained. The pronounced inhibitory effects of Cu2+ on algae growth was not a
      consequence of photoinhibition and could be attributed to direct inhibitory
      effects on the growth process.

PMID- 16291188
TI  - Effects of some environmental parameters on the reproduction and development of a
      tropical marine harpacticoid copepod Nitocra affinis f. californica Lang.
AB  - The effects of salinity, temperature, and light conditions on the reproduction
      and development of harpacticoid copepod, Nitocra affinis f. californica under
      controlled laboratory conditions were determined. Seven different salinity levels
      (5, 10, 15, 20, 25, 30, 35 ppt), four temperatures (20, 25, 30, 35 degrees C),
      three different light intensities (25, 56, 130 micromol m(-2) s(-1)) and
      photoperiods (24 h:0 h, 1 h:23 h, 12 h:12 h LD cycle) were employed in this
      study. The highest (p < 0.05) overall reproduction and fastest development time
      were achieved by copepods reared under 30-35 ppt salinity. The optimum
      temperature required for the maximum reproduction was 30 degrees C while under 30
      degrees C and 35 degrees C the copepod development time was shortest (p < 0.05)
      compared to other temperature levels. The overall reproduction was highest (p <
      0.05) and development rate of N. affinis was shortest (p < 0.05) under lowest
      light intensity (25 micromol m(-2) s(-1)). Continuous light (24 h:0 h LD)
      inhibited the egg production while, continuous darkness (1 h:23 h LD) and 12 h:12
      h LD significantly favoured the overall reproductive activity of the female.
      Photoperiods 1 h:23 h and 12 h:12 h LD yielded highest total (p < 0.05) offspring
      female(-1) coupled with highest (p < 0.05) survival percentage. This study
      illustrated that although N. affinis can tolerate wide range of environmental
      conditions, prolonged exposure to subnormal environments affect its reproduction
      and development. This study showed that this species can be mass cultured for
      commercial purposes and has a potential to be used for toxicity studies due to
      its high reproductive performance fast development and a wide range of tolerance
      to environmental conditions.

PMID- 16291189
TI  - Bioenergetic responses in green lipped mussels (Perna viridis) as indicators of
      pollution stress in Xiamen coastal waters, China.
AB  - Samples of green lipped mussels (Perna viridis) were collected from three sites
      (Huoshao, I'Maluan and Tong'an) around Xiamen coastal waters, where levels of
      various trace organic pollutants have been studied. Samples were also collected
      at a "cleaner" reference site near Dongshan Island for comparison. Clearance
      rate, absorption efficiency and oxygen consumption of the mussels were measured
      under controlled laboratory condition; organic pollutants in their tissues were
      also analyzed. Scope for growth (SFG) was employed as a general biomarker to
      evaluate the stress of pollutants. Specimens from Tong'an site had the lowest SFG
      values (1.14 J/h/g); while specimens from the I'Maluan site and Huoshao site had
      SFG values of 5.01 and 6.72 J/h/g, respectively. Specimens from Dongshan
      (reference site) had a relatively high SFG value of 10.96 J/h/g. There was a
      significant negative correlation between the SFG of the different populations of
      green lipped mussels and the concentration of DDT in their tissues.

PMID- 16291190
TI  - Analysis of 686 expressed sequence tags (ESTs) from the intertidal harpacticoid
      copepod Tigriopus japonicus (Crustacea, Copepoda).
AB  - The intertidal harpacticoid copepod Tigriopus japonicus is an important species
      in the study of marine pollution. To facilitate molecular biomonitoring using T.
      japonicus, we constructed a T. japonicus unidirectional cDNA library using
      lambdaZAP expression vector, excised to pBluescript vector with the aid of helper
      phage, and analyzed 686 randomly picked expressed sequence tags (ESTs) from this
      species. From the 686 ESTs sequenced, we found several functional genes such as
      vitellin, kinases and potential detoxification-related genes. We are now
      preparing a T. japonicus cDNA chip for molecular ecotoxicological studies. In
      this paper, we discuss the potential use of T. japonicus ESTs and their
      importance in ecotoxicology.

PMID- 16291191
TI  - Molecular cloning of vitellogenin cDNA in rockfish (Sebastes schlegeli) and
      effects of 2,2'4,4'5,5'-hexachlorobiphenyl (PCB 153) on its gene expression.
AB  - Many environmental chemicals are known to affect sex steroid production and
      vitellogenesis through agonistic or antagonistic pathways. To investigate the
      estrogenic effect of 2,2'4,4'5,5'-hexachlorobiphenyl (PCB 153) on reproductive
      function, we have constructed a cDNA library and cloned a 320 base sequence
      encoding a partial VTG mRNA of rockfish (rVTG), Sebastes schlegeli. We have
      examined the expression level of rVTG mRNA level by northern blot analysis and
      measured levels of plasma estradiol-17beta (E2) and testosterone (T) by
      radioimmunoassay (RIA). Plasma concentrations of T in female and male injected
      with PCB 153 were not significantly different between two dosages of 0.16 mg/kg
      b.w. and 0.57 mg/kg b.w. However, plasma concentrations of E2 in female fish
      injected with PCB 153 at 0.16 mg/kg b.w. and 0.57 mg/kg b.w. increased after 12 h
      and 24 h. An rVTG mRNA transcript of approximately 4.0 kilo bases was extracted
      from hepatic tissue for northern blot analysis, and the effects of PCB 153 on
      rVTG mRNA expression in vivo with both male and female juvenile rockfish were
      examined. The level of rVTG mRNA expression increased only in female rockfish
      injected with both dose levels of PCB 153 after 48 h of exposure. The results of
      this study suggest that PCB 153 may produce VTG in female through a synergic
      effect with E2 resulting in indirect disruption.

PMID- 16291192
TI  - Size effects of suspended particles on gill damage in green-lipped mussel Perna
      viridis.
AB  - The green-lipped mussels Perna viridis were exposed to <500 microm suspended
      solids (SS) with concentrations of 0 (control), 250, 500, 750 and 1000 mg/L for
      14 days, followed by transferring to clean, filtered seawater for 28 days.
      Results of scanning microscopy showed significantly higher damages to the cilia
      on the frontal surface of the gill filaments than that on the abfrontal surface
      in both demibranchs. Percent ciliary depletion varied with SS concentrations and
      time. No sign of recovery of the gill filaments was observed after the mussels
      were transferred to clean seawater. In a second experiment, mussels were exposed
      to SS with size range from <63, >125-<250 and >250-<500 microm at 600 mg/L,
      together with a control (0 mg/L) for 14 days, followed by transferring to clean,
      filtered seawater for 28 days. Results of scanning microscopy showed significant
      ciliary damages in both the ascending and descending lamellae under the three
      particle size groups as compared with the control. Percent depletion of frontal
      cilia was most serious for the >250-<500 microm size group and least for the <63
      microm size group. However, percent depletion of abfrontal cilia was most serious
      for the >125-<250 microm size group and least for the <63 microm size group. No
      recovery of ciliary damages was observed. The effects of particle size of
      suspended sediments on the morphological damages of gill filaments in the green
      lipped mussels were discussed.

PMID- 16291193
TI  - Toxicity of antifouling biocides to the intertidal harpacticoid copepod Tigriopus
      japonicus (Crustacea, Copepoda): effects of temperature and salinity.
AB  - Intertidal harpacticoid copepods are commonly used in eco-toxicity tests
      worldwide. They predominately live in mid-high shore rock pools and often
      experience a wide range of temperature and salinity fluctuation. Most eco
      toxicity tests are conducted at fixed temperature and salinity and thus the
      influence of these environmental factors on chemical toxicity is largely unknown.
      This study investigated the combined effect of temperature and salinity on the
      acute toxicity of the copepod Tigriopus japonicus against two common biocides,
      copper (Cu) and tributyltin (TBT) using a 2 x 3 x 4 factorial design (i.e. two
      temperatures: 25 and 35 degrees C; three salinities: 15.0 per thousand, 34.5 per
      thousand and 45.0 per thousand; three levels of the biocide plus a control).
      Copper sulphate and tributyltin chloride were used as the test chemicals while
      distilled water and acetone were utilised as solvents for Cu and TBT
      respectively. 96 h-LC50s of Cu and TBT were 1024 and 0.149 microg l(-1)
      respectively (at 25 degrees C; 34.5 per thousand) and, based on these results,
      nominal biocide concentrations of LC0 (i.e. control), LC30, LC50 and LC70 were
      employed. Analysis of Covariance using 'concentration' as the covariate and both
      'temperature' and 'salinity' as fixed factors, showed a significant interaction
      between temperature and salinity effects for Cu, mortality increasing with
      temperature but decreasing with elevated salinity. A similar result was revealed
      for TBT. Both temperature and salinity are, therefore, important factors
      affecting the results of acute eco-toxicity tests using these marine copepods. We
      recommend that such eco-toxicity tests should be conducted at a range of
      environmentally realistic temperature/salinity regimes, as this will enhance the
      sensitivity of the test and improve the safety margin in line with the
      precautionary principle.

PMID- 16291194
TI  - Bioavailability of dissolved organic phosphorus compounds to typical harmful
      dinoflagellate Prorocentrum donghaiense Lu.
AB  - The bioavailability of dissolved organic phosphorus (DOP) compounds to harmful
      alga Prorocentrum donghaiense Lu and its alkaline phosphatase activity (APA) were
      studied. Results showed that P. donghaiense could utilize the test DOP compounds
      such as glucose-6-phosphate (G-6-P), adenosine triphosphate (ATP) and ribonucleic
      acid (RNA) to sustain its growth. Nutrition between the test DOP compounds and
      orthophosphate was comparable. P. donghaiense could utilize intracellular
      phosphorus to sustain growth under depletion of dissolved phosphorus. Variation
      of APA in different test DOP compounds was addressed; the controlling mechanism
      of APA in different DOP media was discussed.

PMID- 16291195
TI  - Placental transfer of arsenic to fetus of Dall's porpoises (Phocoenoides dalli).
AB  - Concentrations of total arsenic and individual arsenic compounds were determined
      in liver, muscle, kidney and blubber of mother and fetus of Dall's porpoises
      collected from off Sanriku, Japan, in the year 2000 to characterize the placental
      transfer of arsenic to fetus in cetaceans. Arsenic was detected in all the
      tissues of Dall's porpoises. Total arsenic concentrations in liver, kidney,
      muscle and blubber were 0.76, 0.69, 0.35 and 0.55 microg/g wet wt, respectively,
      for mother and 0.28, 0.23, 0.26 and 0.07 microg/g wet wt, respectively, for
      fetus. In all the tissues, concentrations of total arsenic in mother Dall's
      porpoise were higher than in fetus. Arsenic speciation revealed that
      arsenobetaine was the major arsenic compound in liver, kidney and muscle of both
      mother and fetus. The percentage of arsenobetaine to total arsenic ranged from
      76.0 to 91.0% in the tissues. Dimethylarsinic acid, arsenocholine, methylarsonic
      acid and an unidentified arsenic compound were also detected in tissues of both
      mother and fetus as minor constituents, whereas tetramethylarsonium ion was not
      detected in tissues of the fetus. These results suggest that arsenobetaine,
      dimethylarsinic acid, arsenocholine and methylarsonic acid are transferable from
      mother to fetus in Dall's porpoises. To our knowledge, this is the first report
      on placental transfer of arsenic compounds to fetus in marine mammals.

PMID- 16291196
TI  - Sedimentary record of polycyclic aromatic hydrocarbons in a sediment core from
      the Pearl River Estuary, South China.
AB  - Owing to the hydrodynamic and sedimentation conditions, the western shoal of the
      Pearl River Estuary (PRE) is known to be an important sink of terrestrial
      substances including particle-associated pollutants from the Pearl River Delta
      (PRD) region. In this study, we report the sedimentary record of polycyclic
      aromatic hydrocarbons (PAHs) during the 20(th) century in a sediment core from
      the western shoal of the PRE. The summation PAH concentration ranged from 59 ng
      g(-1) to 330 ng g(-1) in the core with two distinct peaks. An initial increase of
      summation PAH concentration was found around the 1860s. The amounts of PAHs
      remained relatively constant for roughly 100 years, followed by the first peak in
      the 1950s. Then, there was a decrease in PAH concentration and flux in the 1960s
      and 1970s. A sharp increase of PAH concentration was observed in the early 1980s
      with a maximum concentration in the 1990s. The PAH diagnostic ratios indicated
      that the PAHs in the sediment core were mainly of pyrolytic origin, and that
      atmospheric deposition and land runoff may serve as the important pathways for
      PAHs input to the sediment. The Gross Domestic Product (GDP) was used as an index
      of socioeconomic development in the PRD region, which was correlated positively
      with the changes of PAH concentration and flux in the sediment core. The rapid
      increase in vehicle numbers and energy consumption in the region in the last two
      decades may have contributed to the rapid PAH increase since the early 1980s. The
      results clearly elucidated the impact of regional economic development on the
      estuarine environment.

PMID- 16291198
TI  - Characterization of transboundary POP contamination in aquatic ecosystems of
      Pearl River delta.
AB  - During the past two decades, the rapid development of the Pearl River delta leads
      to substantial accumulation of various toxic organic compounds. This study aims
      to give a preliminary characterization of the existing state of contamination in
      this region and to provide insight into the possible fate of persistent organic
      pollutants (POPs) in this estuary. The available data on POPs in water, river,
      estuarine sediments, soil, and marine organisms within the Pearl River delta are
      compiled. It is shown that it may lead to transboundary POP pollution problems at
      both Hong Kong and Macau Special Administration Regions located at the downstream
      end of the region. It is noted that the levels of DDTs and HCHs in various
      environmental media are at alerting levels and that fresh DDT might still be
      applied illegally within the region. A systematic research is required to
      determine both the temporal and spatial variations of all POPs in various
      carrying media of the Pearl River delta as a whole.

PMID- 16291197
TI  - Organochlorine micropollutants in the Jiulong River Estuary and Western Xiamen
      Sea, China.
AB  - Organochlorine contaminants including 12 polychlorinated biphenyl (PCB) congeners
      and 18 insecticides were determined in water, pore water and sediments of the
      Jiulong River Estuary and Western Xiamen Sea, China. The results showed that the
      levels of the total PCBs ranged from non-detectable to 1500 ng l(-1) in water,
      from 209 to 3870 ng l(-1) in pore water, and from 2.78 to 14.8 ng g(-1) dry
      weight in sediments. Total organochlorine insecticide concentrations were from
      below the limit of detection to 2480 ng l(-1) in water, from 267 to 33400 ng l(
      1) in pore water, and from 4.22 to 46.3 ng g(-1) dry weight in sediments.
      Concentrations of PCBs and insecticides in pore water were significantly higher
      than those in surface water, due to the high affinity of these hydrophobic
      compounds for sediment phase. The PCB congeners with the highest concentrations
      were CB153, CB180 and CB194, which together accounted for 68-87% of total PCBs in
      water, pore water and sediment. Among the hexachlorocyclohexane (HCH) compounds,
      beta-HCH was found to be a major isomer. Analysis of 1,1,1-trichloro-2,2-bis
      chlorophenyl-ethane (DDT) and its metabolites showed that 1,1-dichloro-2[o
      chlorophenyl]-2[p-chlorophenyl]-ethylene (DDE) was dominant in the group. In
      comparison to a 1998 study in the Western Xiamen Sea, levels of organochlorines
      were enhanced due probably to recent inputs and changes in sediments.

PMID- 16291199
TI  - Seasonal and spatial distribution of nonylphenol and IBP in Saemangeum Bay,
      Korea.
AB  - In order to investigate spatial and temporal distribution of organic pollutants
      in the Saemangeum Bay, organophosphorus pesticides (10), alkylphenols (8),
      chlorophenols (2), bisphenol A were analyzed from the surface seawater taken in
      2002-2003. Most of the analytes were not detected in all stations except
      nonylphenol and S-benzyl-O,O-di-isopropyl phosphorothioate (IBP). Concentrations
      of nonylphenol and IBP ranged from ND to 298 ng/l and from ND to 1840 ng/l,
      respectively. The high levels of nonylphenol and IBP were found in the estuary
      areas of Mangyeong and Dongjin River. The levels of nonylphenol and IBP in
      surface seawater varied through seasons and the high levels of nonylphenol and
      IBP were in summer season (August). Based on real time monitoring of IBP and on
      correlation between concentrations of target compounds and contents of salinity
      in seawater, physical mixing and diffusion of seawater were found to be the major
      factors that affect the spatial distribution of IBP and nonylphenol in the
      Saemangeum Bay environment.

PMID- 16291200
TI  - Effects of nutrient enrichment derived from fish farming activities on
      macroinvertebrate assemblages in a subtropical region of Hong Kong.
AB  - To study the correlation between nutrient enrichment derived from fish farming
      activities and changes in macrobenthic assemblages, a one-year field study was
      conducted in Kau Sai Bay marine fish culture zone of Hong Kong. Bimonthly
      sediment samples were collected at six stations: two at the fish cages, two near
      the boundary of the fish culture area, and two reference sites further away from
      the culture area. Sediment physico-chemical characteristics in terms of silt/clay
      fraction, moisture content, total organic carbon (TOC), total Kjeldahl nitrogen
      (TKN) and total phosphorus (TP) were analyzed. The macrobenthos (>0.5 mm) present
      in the sediment were sorted, identified and enumerated. On average, TOC, TKN and
      TP levels at the fish cage stations were 82.8%, 128.5% and 1315.7% higher than
      those at the reference stations, respectively. As a result, the N:P molar ratio
      was greatly reduced from 8.75 at the reference stations to 1.83 at the fish cage
      stations. Univariate and multivariate analyses revealed that diversity of
      macrofauna was significantly reduced and community structure differed at the fish
      cage stations relative to the reference sites. The intermediary stations near the
      fish culture area showed a transitional state of disturbance. Faunal diversity
      was negatively correlated with nutrient level, reflecting the adverse impacts of
      nutrient enrichment derived from fish farming activities on the benthic
      assemblages. Whilst in subtropical Asia-Pacific trash fish is the major feed for
      fish culture resulting in a higher nutrient loading and nutrient ratio
      accumulated in the sediment beneath the fish rafts, the effects of nutrient
      enrichment on macrobenthic assemblages are comparable to that in temperate waters
      owing to relatively high sediment metabolism rate and smaller fish culture scale
      in Hong Kong.

PMID- 16291201
TI  - Microbial modulation in the biomass and toxin production of a red-tide causing
      alga.
AB  - The effect of S10, a strain of marine bacteria isolated from sediment in the
      Western Xiamen Sea, on the growth and paralytic shellfish poison (PSP) production
      in the alga Alexandrium tamarense (A. tamarense) was studied under controlled
      experimental conditions. The results of these experiments have shown that the
      growth of A. tamarense is obviously inhibited by S10 at high concentrations,
      however no evident effect on its growth was observed at low concentrations. Its
      PSP production was also inhibited by S10 at different concentrations, especially
      at low concentrations. The toxicity of this strain of A. tamarense is about (0.95
      12.14) x 10(-6) MU/cell, a peak toxicity value of 12.14 x 10(-6) MU/cell appeared
      on the 14th day, after which levels decreased gradually. The alga grew well in
      conditions of pH 6-8 and salinities of 20-34 per thousand. The toxicity of the
      alga varied markedly at different pH and salinity levels. Toxicity decreased as
      pH increased, while it increased with salinity and reached a peak value at a
      salinity of 30 per thousand, after which it declined gradually. S10 at a
      concentration of 1.02 x 10(9) cells/ml inhibited growth and the PSP production of
      A. tamarense at different pH and salinity levels. S10 had the strongest
      inhibitory function on the growth of A. tamarense under conditions of pH 7 and a
      salinity of 34 per thousand. The best inhibitory effect on PSP production by A.
      tamarense was at pH 7, this inhibitory effect on PSP production did not relate to
      salinity. Interactions between marine bacteria and A. tamarense were also
      investigated using the flow cytometer technique (FCM) as well as direct
      microscope counting. S10 was identified as being a member of the genus Bacillus,
      the difference in 16S rDNA between S10 and Bacillus halmapalus was only 2%. The
      mechanism involved in the inhibition of growth and PSP production of A. tamarense
      by this strain of marine bacteria, and the prospect of using it and other marine
      bacteria in the bio-control of red-tides was discussed.

PMID- 16291202
TI  - Comparative effects of the blue green algae Nodularia spumigena and a lysed
      extract on detoxification and antioxidant enzymes in the green lipped mussel
      (Perna viridis).
AB  - Nodularia spumigena periodically proliferates to cause toxic algal blooms with
      some aquatic animals enduring and consuming high densities of the blue green
      algae or toxic lysis. N. spumigena contains toxic compounds such as nodularin and
      lipopolysaccharides. This current work investigates physiological effects of
      exposure from bloom conditions of N. spumigena cells and a post-bloom lysis.
      Biochemical and antioxidative biomarkers were comparatively studied over an acute
      3-day exposure. In general, a post-bloom N. spumigena lysis caused opposite
      physiological responses to bloom densities of N. spumigena. Specifically,
      increases in glutathione (GSH) and glutathione peroxidase (GPx) and decreases in
      glutathione S-transferase (GST) were observed from the N. spumigena lysis. In
      contrast, N. spumigena cell densities decreased GSH and increased GST and lipid
      peroxidation (LPO) in mussels. Findings also suggest that at different stages of
      a toxic bloom, exposure may result in toxic stress to specific organs in the
      mussel.

PMID- 16291203
TI  - The relationship between soft-bottom macrobenthic communities and environmental
      variables in Singaporean waters.
AB  - Univariate and multivariate methods were used to study soft-bottom macrobenthos
      collected in December 2002 from the coastal waters of Singapore. The univariate
      parameters and community structure of benthic communities were related to
      environmental variables. Three samples were taken with a 0.1 m2 Van Veen grab (33
      x 30 x 15 cm) at each station from 12 sampling stations of two different
      geographical areas. The water depth ranged from 6.5 m to 34.0 m. The mean values
      of species number, abundance and species diversity (H') were 24 species/grab, 77
      animals/grab and 3.35/grab, respectively. A total of 172 species was recorded.
      Total petroleum hydrocarbons were strongly negatively related to species number,
      abundance and species diversity, suggesting that petroleum hydrocarbons have
      harmful effects on macrobenthic communities. The BIO-ENV analyses for all
      stations identified median particle size, silt-clay content, salinity and Zn as
      the major environmental variables influencing the infaunal patterns. However,
      separate analyses for two areas produced stronger correlations and different best
      correlated environmental variable combinations. Total petroleum hydrocarbons were
      the only common factor in both areas, showing the importance of petroleum
      contamination in determining the community structure of benthic infauna in
      Singaporean waters.

PMID- 16291204
TI  - Changes in the marine pollution management system in response to the Amorgos oil
      spill in Taiwan.
AB  - The Marine Pollution Control Act (MPCA) of Taiwan was promulgated on November 1,
      2000, with the specific aim of controlling marine pollution, safeguarding public
      health, and promoting the sustainable use of marine resources. In addition to
      land-based pollution, oil spills are one of the most significant threats to the
      local marine environment largely on account of the some 30,000 tankers which pass
      through Taiwan's coastal waters each year. In January 2001, two months after the
      enactment of this newly-introduced law, a Greek merchant vessel, the Amorgos ran
      aground in the vicinity of a national park on the southern tip of Taiwan, causing
      a serious oil spill and leading to considerable changes with regard to the marine
      pollution management system. The incident brought to the forefront many serious
      problems, such as a lack of experience, expertise as well as equipment required
      to respond to such disasters, as well as the ambiguous, unclear jurisdiction
      among related agencies. Thus, this paper reviews the incident of the Amorgos
      spill, identifies the major issues and lessons learned, and proposes several
      recommendations in an effort for Taiwan to further improve its marine pollution
      management system.

PMID- 16291205
TI  - A study on the treatment of antifouling paint waste from shipyard.
AB  - A study on the treatment of antifouling paint waste from shipyards, including
      sandblast waste and ship hull washing wastewater, was performed. The sandblast
      waste could be effectively detoxified by heat treatment, and the efficiency was
      affected by the temperature of the heating vessel and treatment time. The removal
      efficiency of total organotin compounds from the sandblast waste was over 99% at
      1000 degrees C and treatment for 1 h. For the treatment of ship hull washing
      wastewater by the solvent extraction, ship diesel was a good solvent for the
      tributyltin (TBT) extraction, and the proper amount of solvent was about 10 mL
      for TBT extraction from 1L of wastewater. The extraction efficiency of TBT was
      significantly affected by the agitation intensity. The TBT in the wash wastewater
      was rapidly extracted within 1 h. The level of the TBT residual in the wastewater
      extracted for 1h was 2.8 microg L(-1), and this was further decreased to 0.8
      after 5 h extraction.

PMID- 16291206
TI  - Isolation of PAH-degrading bacteria from mangrove sediments and their
      biodegradation potential.
AB  - Surface sediment samples were collected from seven mangrove swamps in Hong Kong
      SAR with different degrees of contamination. The total concentrations of 16 PAHs
      in these sediments ranged from 169.41 to 1058.37 ng g(-1) with the highest
      concentration found in Ma Wan and the lowest in Kei Ling Ha Lo Wai mangrove
      swamp. In each swamp, three bacterial consortia were enriched from sediments
      using phenanthrene (Phe) as the sole carbon and energy source, and individual
      bacterial colony showing Phe degradation was isolated and identified by 16S rDNA
      gene sequence. The consortia enriched from Sai Keng and Ho Chung sediments had
      highest ability to degrade mixed PAHs in liquid medium, with 90% Phe and Fla
      (fluoranthene) degraded in 7 days. On the other hand, Kei Ling Ha Lo Wai-enriched
      consortia degraded less than 40% Phe and Fla. Pyrene (Pyr) was hardly degraded by
      the consortia enriched from sediments. Bacterial isolates, namely Rhodococcus
      (HCCS), Sphingomonas (MWFG) and Paracoccus (SPNT) were capable to degrade mixed
      PAHs (Phe + Fla + Pyr). Their degradation percentages could be lower, comparable
      or even higher than their respective enriched consortia, depending on the
      consortium and the type of PAH compounds. These results suggest that PAH
      degrading bacteria enriched from mangrove sediments, either as a mixed culture or
      as a single isolate could be used for PAHs bioremediation.

PMID- 16291207
TI  - Bioremediation of oil-contaminated sediments on an inter-tidal shoreline using a
      slow-release fertilizer and chitosan.
AB  - A 95-day field trial on the bioremediation of oil in beach sediment using
      Osmocote and chitosan was conducted on an inter-tidal foreshore in Singapore.
      Osmocote was the key factor in enhancing nutrient levels in sediments, the
      metabolic activity of the indigenous microbial biomass, and the biodegradation of
      aliphatics and polycyclic aromatic hydrocarbons (PAHs) with ring number of 2 and
      3. In contrast, chitosan did not enhance these parameters in the presence of
      Osmocote. However, the addition of chitosan to Osmocote amended sediments
      significantly enhanced biodegradation of recalcitrant 4-6-ring PAHs. This is most
      likely due to the high oil adsorbancy capacity of chitosan, which enhances the
      bioavailability of high ring number PAHs to the microbial biomass.

PMID- 16291208
TI  - An unsteady three-dimensional eutrophication model in Tolo harbour, Hong Kong.
AB  - The eutrophication phenomenon often leads to undesirable water quality. This
      paper delineates an unsteady three-dimensional finite difference numerical model
      for eutrophication dynamics in the coastal waters of Tolo harbour, Hong Kong,
      employing the numerically generated, boundary-fitted, orthogonal curvilinear grid
      system as well as a grid "block" technique. It models the transport and
      interaction of nine water quality constituents. Adjustments of values of some
      kinetic coefficients in the model are effected through calibration with field
      data. It is demonstrated that the model can reasonably reproduce the interactions
      amongst all the water quality constituents, the eutrophication processes and, in
      particular, the featured bottom water anoxic condition during the summer in Tolo
      harbour.

PMID- 16291209
TI  - Use of slow-release fertilizer and biopolymers for stimulating hydrocarbon
      biodegradation in oil-contaminated beach sediments.
AB  - Nutrient concentration and hydrocarbon bioavailability are key factors affecting
      biodegradation rates of oil in contaminated beach sediments. The effect of a slow
      release fertilizer, Osmocote, as well as two biopolymers, chitin and chitosan, on
      the bioremediation of oil-spiked beach sediments was investigated using an open
      irrigation system over a 56-day period under laboratory conditions. Osmocote was
      effective in sustaining a high level of nutrients in leached sediments, as well
      as elevated levels of microbial activity and rates of hydrocarbon biodegradation.
      Chitin was more biodegradable than chitosan and gradually released nitrogen into
      the sediment. The addition of chitin or chitosan to the Osmocote amended
      sediments enhanced biodegradation rates of the alkanes relative to the presence
      of Osmocote alone, where chitosan was more effective than chitin due to its
      greater oil sorption capacity. Furthermore, chitosan significantly enhanced the
      biodegradation rates of all target polycyclic aromatic hydrocarbons.

PMID- 16291210
TI  - Site-specific DNA recombinases as instruments for genomic surgery.
AB  - Site-specific DNA recombinases can "cut and paste" DNA. For example, they can
      promote excision of specific DNA segments or insertion of new DNA segments in
      specific places. However, natural recombinases act only at their cognate
      recombination sites, so current applications are limited to genetically modified
      organisms in which these sites have been introduced into the genome. Transposases
      also catalyze DNA rearrangements; they promote insertion of specific DNA
      sequences but at nonspecific locations. Applicability of site-specific
      recombinases and transposases in experimental genetics, biotechnology, and gene
      therapy would be much wider if they could be re-engineered so as to act
      specifically at chosen sequences within an organism's natural genome. This review
      will discuss progress towards the creation of such "designer" recombinases.

PMID- 16291211
TI  - Human clinical trials of plasmid DNA vaccines.
AB  - This article gives an overview of DNA vaccines with specific emphasis on the
      development of DNA vaccines for clinical trials and an overview of those trials.
      It describes the preclinical research that demonstrated the efficacy of DNA
      vaccines as well as an explication of the immunologic mechanisms of action. These
      include the induction of cognate immune responses, such as the generation of
      cytolytic T lymphocytes (CTL) as well as the effect of the plasmid DNA upon the
      innate immune system. Specific issues related to the development of DNA as a
      product candidate are then discussed, including the manufacture of plasmid, the
      qualification of the plasmid DNA product, and the safety testing necessary for
      initiating clinical trials. Various human clinical trials for infectious diseases
      and cancer have been initiated or completed, and an overview of these trials is
      given. Finally, because the early clinical trials have shown less than optimal
      immunogenicity, methods to increase the potency of the vaccines are described.

PMID- 16291212
TI  - Genetic and environmental influences on antisocial behaviors: evidence from
      behavioral-genetic research.
AB  - This article reviews behavioral-genetic research into human antisocial behavior.
      The focus is on studies of antisocial behavior that have been leading the way in
      investigating environmental and genetic influences on human behavior. The first
      generation of studies, which provided quantitative estimates attesting that genes
      and environments each influence about half of the population's variation in
      antisocial behaviors is interpreted. Then how behavioral-genetic methods are
      being applied to test developmental theory and to detect environmental causes of
      antisocial behavior is illustrated. Evidence for interactions between genes and
      the environment in the etiology of antisocial behavior is also examined. The
      article ends by envisioning future work on gene-environment interplay in the
      etiology of antisocial behavior.

PMID- 16291213
TI  - Genetics of graviperception in animals.
AB  - Gravity is a constant stimulus for life on Earth and most organisms have evolved
      structures to sense gravitational force and incorporate its influence into their
      behavioral repertoire. Here we focus attention on animals and their diverse
      structures for perceiving and responding to the gravitational vector-one of the
      few static reference stimuli for any mobile organism. We discuss vertebrate,
      arthropod, and nematode models from the perspective of the role that genetics is
      playing in our understanding of graviperception in each system. We describe the
      key sensory structures in each class of organism and present what is known about
      the genetic control of development of these structures and the molecular
      signaling pathways operating in the mature organs. We also discuss the role of
      large genetic screens in identifying specific genes with roles in
      mechanosensation and graviperception.

PMID- 16291214
TI  - Retroviral DNA integration--mechanism and consequences.
AB  - Integration of retroviral cDNA into the host cell chromosome is an essential step
      in its replication. This process is catalyzed by the retroviral integrase
      protein, which is conserved among retroviruses and retrotransposons. Integrase
      binds viral and host DNA in a complex, called the preintegration complex (PIC),
      with other viral and cellular proteins. While the PIC is capable of directing
      integration of the viral DNA into any chromosomal location, different
      retroviruses have clear preferences for integration in or near particular
      chromosomal features. The determinants of integration site selection are under
      investigation but may include retrovirus-specific interactions between integrase
      and tethering factors bound to the host cell chromosomes. Research into the
      mechanisms of retroviral integration site selection has shed light on the
      phenomena of insertional mutagenesis and viral latency.

PMID- 16291216
TI  - The preparation of anaerobic nitric oxide solutions for the study of heme model
      systems in aqueous and nonaqueous media: some consequences of NO x impurities.
AB  - The reactions of nitric oxide (NO) have been a subject of broad interest among
      biochemists and chemists. This report discusses several quantitative techniques
      to handle and use NO gas that has been delivered from compressed cylinders. The
      focus is on techniques that minimize and avoid the presence of oxygen impurities,
      which when present, result in the generation of other nitrogen oxides (NO x).
      These NO x species typically exhibit different reactivity, and unless removed or
      quantified, their presence will complicate studies focusing on the reactions
      caused by NO itself.

PMID- 16291217
TI  - The NOtizer--a device for the convenient preparation of diazen-1-ium-1,2
      diolates.
AB  - N-bound diazen-1-ium-1,2-diolates, also known as NONOates or "solid nitric oxide"
      (NO), have become popular tools in biomedical research since the discovery of NO
      as a very important multifunctional endogenous messenger. In contrast to other
      well-known NO donors, NONOates are capable of releasing NO spontaneously in
      aqueous media. The rate of NO liberation is determined by the molecular structure
      of the diazeniumdiolate and the pH value and temperature of the medium in which
      it is dissolved. In this chapter, we introduce a novel device (the NOtizer) for
      simple and convenient preparation of diazeniumdiolates. It not only enables the
      user to provide all the necessary conditions for reliable synthesis such as
      anaerobic conditions and high pressure of NO gas in the translucent reaction
      chamber but also includes software that records the course of pressure and
      temperature online and calculates the consumption of NO by the reaction. The plot
      of the pressure decay shows the user completion of the reaction and allows the
      user to study kinetic characteristics from synthesis of different NONOates. A
      brief guide for the synthesis of PYRRO/NO, DEA/NO, PAPA/NO, SPER/NO, and DETA/NO,
      which are the most widely applied diazeniumdiolates, is presented in this
      chapter. Finally, characteristics of NONOates that need to be considered
      concerning analytics and storage are mentioned.

PMID- 16291218
TI  - Quantum mechanical determinations of reaction mechanisms, acid base, and redox
      properties of nitrogen oxides and their donors.
AB  - This chapter reviews computational methods based on quantum mechanics and
      commonly used commercial programs for the exploration of chemical phenomena,
      particularly in the field of nitrogen oxides. Examples from the literature are
      then used to demonstrate the application of these methods to the chemistry and
      biochemistry of various nitrogen oxides. These examples include determining
      reaction mechanisms using computed reaction energies, predicting rates of
      reactions using transition state theory, and determining chemical properties such
      as hydration equilibria, pKa's, and reduction potentials.

PMID- 16291219
TI  - Electrochemical and spectrophotometric methods for evaluation of NO dissociation
      rate constants from nitrosyl metal complexes activated through reduction.
AB  - Electrochemical and spectrophotometric methods are described for measuring the
      rate of nitric oxide (NO) dissociation (k(NO)) from coordination compounds.
      Electrochemical methods based on double-potential step chronoamperometry and
      rotating ring-disc electrode voltammetry techniques proved to be suitable for
      measuring NO dissociation from 0.03 to 4.0 s(-1). The spectrophotometric method
      using an ancillary ligand as a colorimetric indicator is illustrated on measuring
      k(-NO)=0.002 s(-1). This methodology is limited only by the rate of the ancillary
      ligand substitution.

PMID- 16291220
TI  - Sensitive and isotope selective (14NO/15NO) online detection of nitric oxide by
      faraday-laser magnetic resonance spectroscopy.
AB  - The monitoring of trace amounts of nitric oxide (NO) is of great interest for
      biomedical applications. High-resolution infrared spectroscopy, like laser
      magnetic resonance spectroscopy (LMRS), is a versatile technique for the
      quantitative and isotope-selective analysis of low concentrations of NO. The
      ability to distinguish between different NO isotopomeres is of special interest
      for pharmaceutical and biomedical applications when tracer investigations are
      performed. With LMRS using Faraday modulation, a sensitivity of 1-2 ppbV for 15NO
      can be achieved. With further improvements and development of the sensor, we
      expect a sub-ppbV sensitivity.

PMID- 16291221
TI  - Qualitative and quantitative determination of nitrite and nitrate with ion
      chromatography.
AB  - Reactions of nitrogen monoxide and peroxynitrite often yield nitrite and nitrate
      as stable end products. The simultaneous detection of these two ions by anion
      chromatography with conductivity detection is described. The chromatographic
      system used is similar to conventional isocratic or gradient high-performance
      liquid chromatography equipment. The columns are packed with ion-exchanging
      resins instead of silica-derived adsorbents. Conductivity, though inherently
      nonspecific, has the advantage of covering a linear dynamic signal range of five
      orders of magnitude, which is far better than spectroscopic techniques; these are
      generally limited to two orders of magnitude. Typical run times per chromatogram
      are 15-30 min, and sample and standard concentrations can be between 100 nM and
      10 mM. Injection volumes vary from 5 to 200 microl. Unlike with the Griess
      method, which determines only nitrite, a true mass balance from independent
      signals can be obtained if nitrate and nitrite are the only products.

PMID- 16291222
TI  - Electrochemical detection of nitric oxide in biological fluids.
AB  - The challenges that must be overcome in order to detect nitric oxide (NO) in
      biological fluids include its low physiological concentration (1-nM) and its
      short half-life (a few seconds or less). Electrochemistry is capable of making
      such measurements, if certain principles, both biological and electrochemical,
      are kept in mind. We discuss these principles and demonstrate an example of
      practical measurement by detecting NO release in a drop of blood suspended within
      the reference electrode of an electrochemical cell. We elicit the NO release by
      decreasing the oxygen concentration in the gaseous atmosphere surrounding the
      drop.

PMID- 16291224
TI  - The ESR method to determine nitric oxide in plants.
AB  - Nitric oxide (NO) plays an important role not only in animal system but also in
      plant system. We developed a method to detect NO free radical in plant system
      using electron spin resonance (ERS) spin trapping technique. The adduct (DETC)2
      Fe2+-NO in plant can be extracted by organic solvent and then measured on an ESR
      spectrometer at room temperature (indirect method) or can be measured in live
      plant on an ESR spectrometer, but the water in the plant has to be partially
      dehydrated (direct method).

PMID- 16291223
TI  - Simultaneous detection of NO and ROS by ESR in biological systems.
AB  - A large body of evidence shows that the generation of nitric oxide (NO) and
      reactive oxygen species (ROS) and the rate of ROS/NO play an important role in
      the biological system. We developed a method to simultaneously detect NO free
      radical and ROS in biological systems using ERS spin trapping technique. The
      adduct (DETC)2-Fe2+-NO and N-tert- butyl-alpha-phenylnitrone (PBN)-ROS in
      biological systems can be extracted by organic solvent and then measured on an
      electron spin resonance (ESR) spectrometer at room temperature because the g =
      2.035 of (DETC)2-Fe2+-NO is different from that of PBN-ROS (g = 2.005) and their
      ESR signals can be separated clearly. Using this method, we measured the
      production of NO and ROS in plant and animal systems.

PMID- 16291225
TI  - S-nitrosothiol formation.
AB  - Protein and peptide S-nitrosothiols (SNOs) are involved in guanylate cyclase
      independent signaling associated with nitric oxide synthase (NOS) activation. As
      a general rule, SNO formation requires the presence of an electron acceptor such
      as Cu2+. Various proteins have been identified that catalyze SNO formation,
      including NOS itself, ceruloplasmin, and hemoglobin. Biochemical evidence
      suggests the existence of other SNO synthases and NOS-associated proteins
      involved in SNO formation following NOS activation. Indeed, both hydrophilic and
      hydrophobic consensus motifs have been identified that favor protein S
      nitrosylation. Inorganic SNO formation appears also to occur in biological
      systems at low pH levels and/or in membranes. Once formed, SNOs localized to
      specific cellular compartments signal specific effects, ranging from gene
      regulation to ion channel gating. Indeed, the number of cellular and
      physiological functions appreciated to be regulated through SNO synthesis,
      localization, and catabolism is increasing. Although research into SNO
      biosynthesis is in its infancy, the importance of this field of biochemistry has
      been confirmed repeatedly by investigators from a broad spectrum of disciplines.

PMID- 16291226
TI  - Detection and characterization of protein nitrosothiols.
AB  - Protein S-nitrosylation is a post-translational modification of cysteine residues
      elicited by nitric oxide (NO). Detection and quantification of protein
      nitrosothiols remains a challenge because of the lability of the nitrosothiol
      moiety. Here, we describe approaches for labeling S-nitrosylated proteins with
      affinity and radioactive tags to facilitate their detection, purification, and
      identification.

PMID- 16291227
TI  - Detection of nitrosothiols and other nitroso species in vitro and in cells.
AB  - The nitric oxide (NO)-mediated nitrosation of peptides and proteins may play
      important roles in normobiology and pathobiology. With the realization that S
      nitrosothiols (RSNOs) participate in the transport, storage, and delivery of NO,
      as well as posttranslational modifications in cell signaling and inflammatory
      processes, there is an increasing need for the detection of nitrosothiols (RSNOs)
      and other nitroso species in cells and tissues. In this chapter, we describe the
      utilization of a gas phase chemiluminescence-based assay and "biotin switch"
      method for the detection of nitroso species in cells. These methods are sensitive
      enough to quantify and contrast the different pools of nitroso species that may
      coexist under physiologically relevant conditions. They also provide the means to
      characterize and identify proteins that may represent specific targets for
      nitrosation reactions.

PMID- 16291228
TI  - Detection and identification of S-nitrosylated proteins in endothelial cells.
AB  - Nitric oxide performs some of its direct effects by the induction of various
      protein posttranslational modifications. Among them, S-nitrosylation of cysteines
      has gained increasing attention and has been postulated as a signaling mechanism.
      However, there are still many technical limitations for the detection and
      identification of this posttranslational modification in cell proteins, and some
      of them are directly related to the lability of the nitrosothiol bond. We
      describe protocols for applying a derivatization technique, the biotin switch,
      which substitutes the S-nitrosylation for a biotinylation in the detection and
      proteomic identification of S-nitrosylated proteins in intact cells.

PMID- 16291229
TI  - S-nitrosylation in Parkinson's disease and related neurodegenerative disorders.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder characterized by
      impairment in motor function. PD is mostly sporadic, but rare familial cases are
      also found. The exact pathogenic mechanism is not fully understood, but both
      genetic and environmental factors are known to be important contributors. In
      particular, oxidative stress mediated through nitric oxide (NO) is believed to be
      a prime suspect in the development of PD. NO can exert its effect by modifying
      different biological molecules, and one of these modifications is through S
      nitrosylation. Because of the liable nature of S-nitrosylation, a number of
      methods are often used to study this modification. We have successfully employed
      some of these methods and showed that a familial related protein, parkin, can be
      S-nitrosylated and provide a common pathogenic mechanism for sporadic and
      familial PD.

PMID- 16291230
TI  - Dynamic assessment of nitration reactions in vivo.
AB  - Assessment of protein nitration is commonly used as a footprint for the formation
      of reactive nitrogen species in vivo. However, one of the major disadvantages of
      measuring nitrotyrosine in proteins is that nitrated proteins are broken down at
      variable rates, and the resulting free nitrotyrosine is taken up by cells,
      metabolized, and excreted. We have discovered a biochemical pathway in which
      circulating para-hydroxyphenylacetic acid (PHPA) undergoes nitration to form 3
      nitro-4-hydroxyphenylacetic acid (NHPA), which is rapidly excreted in the urine.
      Using various animal models, we have shown that measurement of urinary NHPA can
      be used to assess the formation of reactive nitrogen species in vivo.

PMID- 16291231
TI  - Protein nitration in biological aging: proteomic and tandem mass spectrometric
      characterization of nitrated sites.
AB  - Proteomic techniques for the identification of 3-nitrotyrosine-containing
      proteins in various biological systems are described with emphasis on the direct
      mass spectrometric detection and sequencing of 3-nitrotyrosine-containing
      peptides. Strengths and weaknesses of various separation and mass spectrometric
      techniques are discussed. Some examples for the MS/MS analysis of nitrated
      peptides obtained from aging rat heart and skeletal muscle are provided, such as
      nitration of Tyr105 of the mitochondrial electron-transfer flavoprotein and Tyr14
      of creatine kinase.

PMID- 16291232
TI  - HPLC-electrochemical detection of tocopherol products as indicators of reactive
      nitrogen intermediates.
AB  - The nitric oxide (NO) free radical serves diverse functions in mammalian
      physiology, facilitating processes that range from vasodilation to
      neurotransmission to host-pathogen defense. Despite the fascinating biochemical
      utility of this small diatomic gas, NO and its derived oxidation or reduction
      products [reactive nitrogen species (RNSs) or reactive nitrogen intermediates
      (RNIs)] can be deleterious to cells and tissues under conditions of
      pathophysiology. Recent years have witnessed a tremendous and continuing
      scientific interest in RNI, both as targets for pharmacotherapy and as biomarkers
      for disease. Accordingly, methods have been developed to quantify RNI in real
      time under controlled experimental conditions. Such methods usually employ either
      electron paramagnetic resonance (EPR) spin traps (see ) or electrochemical
      sensors (Cserey and Gratzl, 2001). Nonetheless, the transient nature of NO and
      RNIs often precludes their routine assessment in animal experiments or human
      clinical studies where tissue must be archived and stored at a later time. To
      circumvent these limitations, methods have been invented to detect and quantify
      stably nitrated products of RNI reaction with ambient biomolecules. This chapter
      describes the theory and methodology for detection of lipid-phase tocopherol
      nitration products, especially 5-nitro-gamma-tocopherol (5-NO2-gammaT) by high
      performance liquid chromatography with electrochemical detection (HPLC-ECD).

PMID- 16291233
TI  - Hydrophobic tyrosyl probes for monitoring nitration reactions in membranes.
AB  - In this chapter, the upregulation of the proteasomal enzymes in response to
      nitric oxide (NO) in endothelial cells is discussed. The cytoprotective effects
      of NO are discussed in relation to iron homeostasis, oxidative stress, and the
      cellular proteasomal function. The role of NO-dependent proteolytic signaling
      mechanism is important to the overall understanding of the redox signaling in
      oxidative endothelial cell injury.

PMID- 16291234
TI  - Synthesis of peroxynitrite from nitrite and hydrogen peroxide.
AB  - We report a simple method for the synthesis of peroxynitrite from nitrite and
      hydrogen peroxide that can generate hundreds of milliliters of 180 mM
      peroxynitrite within 1 h from start to finish. It can be scaled down to make
      small quantities of isotope-labeled peroxynitrite. The method requires only a
      syringe pump and tubing connectors and is feasible for any biochemical
      laboratory. Unreacted hydrogen peroxide is eliminated with manganese dioxide,
      using an improved preparation compared to commercially available manganese
      dioxide. A number of contaminants were detected by mass spectrometry in
      peroxynitrite solutions cleaned with commercially purchased manganese dioxide.
      Nitrite contamination of the peroxynitrite solution is less than 2% as determined
      using the Griess method. The residual contaminants are principally 0.28 M sodium
      chloride and 0.1 M sodium hydroxide, which pose few problems when peroxynitrite
      is diluted for use in biological experiments.

PMID- 16291235
TI  - Peroxynitrite-dependent upregulation of SRC kinases in red blood cells:
      strategies to study the activation mechanisms.
AB  - Several studies have demonstrated that treatment of cells with oxidants, and in
      particular with peroxynitrite, may cause the upregulation of tyrosine
      phosphorylation signaling. In erythrocytes, peroxynitrite induces tyrosine
      phosphorylation of the major intrinsic membrane protein, band 3. A closer look at
      the enzymes involved revealed that the effect of peroxynitrite was due to the
      inhibition of phosphotyrosine phosphatases and/or to the activation of src
      kinases. The activity of src kinases is modulated not only by phosphatases and
      other kinases but also through redox modification of cysteine residues:
      Peroxynitrite can, thus, affect src kinase activity by means of direct and
      indirect mechanisms. In this chapter, we describe the different pathways leading
      to src kinase activation and the experimental procedures that can be performed to
      reveal the activation mechanism. The aim is to provide a more general strategy
      adaptable to different cell types and different oxidants.

PMID- 16291236
TI  - Hemoglobin and red blood cells as tools for studying peroxynitrite biochemistry.
AB  - Oxyhemoglobin represents a relevant intravascular sink of peroxynitrite. Indeed,
      peroxynitrite undergoes a fast isomerization (k = 1.7 x 10(4)M(-1)s(-1)) to
      nitrate in the presence of oxyhemoglobin; the reaction mechanism is complex and
      leads to methemoglobin and superoxide radical as additional products and a small
      amount (approximately 10%) of transient species, including ferrylhemoglobin,
      nitrogen dioxide, and globin-derived radicals. The mechanism of the reaction
      could be solved only after extensive quantitative analysis of reactants,
      intermediates, and products and setting up experimental conditions that favor
      direct reactions of peroxynitrite with hemoglobin versus peroxynitrite decay
      through proton- or carbon dioxide-catalyzed homolysis. Additionally,
      oxyhemoglobin has been used as a "reporter" molecule of peroxynitrite diffusion
      from extracellular to intracellular compartments, using red blood cells (RBCs) as
      a model system. In RBCs, peroxynitrite diffusion across the membrane is favored
      by the large abundance of anion channels, and average transit distances can vary
      as a function of cell density. Indeed, we have developed a mathematical model
      that incorporates competition between the extracellular consumption of
      peroxynitrite and the permeation to the erythrocytes as a function of the average
      diffusion distances. The RBC model presented herein serves to estimate biological
      diffusion distances of peroxynitrite in the presence of relevant molecular
      targets, and the theoretical approach can be successfully applied to study the
      diffusion of peroxynitrite in other cellular/tissue systems.

PMID- 16291237
TI  - Quantification of 3-nitrotyrosine levels using a benchtop ion trap mass
      spectrometry method.
AB  - Oxidative damage by reactive nitrogen species is linked to the pathogenesis of
      numerous inflammatory disorders, including atherosclerosis. 3-Nitrotyrosine
      (NO2Tyr), a posttranslational modification of proteins generated by reactive
      nitrogen species, serves as a "molecular fingerprint" for protein modification by
      nitric oxide (NO)-derived oxidants. Studies demonstrate that systemic levels of
      protein-bound NO2Tyr serve as an independent predictor of cardiovascular risks
      and are modulated by statin therapy. Measurement of NO2Tyr in biological matrices
      may thus serve both as a quantitative index of nitrative stress in vivo and an
      important new prognostic marker of clinical relevance. Analytical methods for the
      accurate detection and quantification of trace levels of NO2Tyr in biological
      tissues and fluids are, thus, of considerable interest. Here, we describe a
      rapid, sensitive, and specific method for the quantification of NO2Tyr in
      biological matrices using readily available benchtop ion-trap mass spectrometry
      instrumentation (e.g., LCQDeca) combined with high-performance liquid
      chromatography (HPLC) interface. Through judicious use of stable isotopically
      labeled precursors as synthetic internal standards, the tandem mass spectrometric
      method described simultaneously adjusts for potential intrapreparative sample
      losses and monitors potential artifactual generation of NO2Tyr during processing.
      The described method permits rapid and reproducible quantification of NO2Tyr in
      biological and clinical specimens at the 100 fmol on column detection limit and
      should prove useful for studies defining the impact of reactive nitrogen species
      in cardiovascular disease and other inflammatory disorders.

PMID- 16291238
TI  - Mapping sites of tyrosine nitration by matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - Protein tyrosine nitration is an important part of nitric oxide biology. This
      posttranslational modification occurs under normal physiological conditions and
      is substantially enhanced under various pathological conditions. Studies reveal
      that protein tyrosine nitration is a dynamic and selective process that
      influences protein function and turnover and can be considered a diagnostic
      biomarker of pathology. The identification of nitrated tyrosine residues directly
      within any given nitrated protein is important for studies on in vivo mechanisms
      of nitration and for the explanation of functional consequences of nitration.
      Specific nitrated tyrosines in given proteins may be also more informative as
      oxidative biomarkers than overall nitrotyrosine levels. However, localization of
      the sites of nitration remains a methodological challenge. Mass spectrometry (MS)
      is an ideal method for identifying nitrated tyrosines in proteins because of its
      sensitivity and specificity. This chapter is not intended to thoroughly discuss
      the various MS-based approaches for nitrotyrosine identification and merely
      focuses on the analysis of peptides containing nitrotyrosine by matrix-assisted
      laser desorption ionization MS (MALDI-MS). The data summarized show that the
      MALDI-MS pattern of a tyrosine-nitrated peptide includes the unique combination
      of ions that provides unequivocal evidence for the presence of nitrotyrosine in a
      given peptide and could be used for mapping sites of tyrosine nitration in
      proteins.

PMID- 16291239
TI  - Peroxynitrite in the pathogenesis of Parkinson's disease and the neuroprotective
      role of metallothioneins.
AB  - Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic
      neurons in the substantia nigra zona compacta and in other subcortical nuclei
      associated with a widespread occurrence of Lewy bodies. The causes of cell death
      in Parkinson's disease are still poorly understood, but a defect in mitochondrial
      oxidative phosphorylation and enhanced oxidative stress has been proposed. We
      have examined 3-morpholinosydnonimine (SIN-1)-induced apoptosis in control and
      metallothionein-overexpressing dopaminergic neurons, with a primary objective to
      determine the neuroprotective potential of metallothionein (MT) against
      peroxynitrite-induced neurodegeneration in PD. SIN-1 induced lipid peroxidation
      and triggered plasma membrane blebbing. In addition, it caused DNA fragmentation,
      alpha-synuclein induction, and intramitochondrial accumulation of metal ions
      (copper, iron, zinc, and calcium), and it enhanced the synthesis of 8-hydroxy-2
      deoxyguanosine. Furthermore, it downregulated the expression of Bcl-2 and
      poly(adenosine diphosphate-ribose) polymerase, but upregulated the expression of
      caspase-3 and Bax in dopaminergic (SK-N-SH) neurons. SIN-1 induced apoptosis in
      aging mitochondrial genome knockout cells, alpha-synuclein-transfected cells,
      metallothionein double-knockout cells, and caspase-3-overexpressed dopaminergic
      neurons. SIN-1-induced changes were attenuated with selegiline or in
      metallothionein-transgenic striatal fetal stem cells. SIN-1-induced oxidation of
      dopamine (DA) to dihydroxyphenylacetaldehyde (DopaL) was attenuated in
      metallothionein-transgenic fetal stem cells and in cells transfected with a
      mitochondrial genome, and was enhanced in aging mitochondrial genome knockout
      cells, in metallothionein double-knockout cells, and caspase-3 gene
      overexpressing dopaminergic neurons. Selegiline, melatonin, ubiquinone, and
      metallothionein suppressed SIN-1-induced downregulation of a mitochondrial genome
      and upregulation of caspase-3 as determined by reverse transcription polymerase
      chain reaction. These studies provide evidence that nitric oxide synthase
      activation and peroxynitrite ion overproduction may be involved in the
      etiopathogenesis of PD, and that metallothionein gene induction may provide
      neuroprotection.

PMID- 16291240
TI  - Yeast model systems for examining nitrogen oxide biochemistry/signaling.
AB  - The yeast Saccharomyces cerevisiae is an ideal model system for examining
      fundamental nitrogen oxide biochemistry. The utility of this model system lies in
      both the similarities and the differences between yeast and mammalian cells. The
      similarities between the two systems, with regards to many of the fundamental
      biochemical processes, allow studies in yeast to be extrapolated to mammalian
      systems. On the other hand, yeast has distinct differences that allow, for
      example, the facile examination of O2, pH, and genetic dependencies on a number
      of nitrogen oxide-mediated processes. Thus, the yeast system is amenable to
      experimentation that is otherwise problematic or impossible in mammalian systems.
      Herein, we present several examples of the utility of the yeast model system for
      studying the intimate details of basic nitrogen oxide biochemistry.

PMID- 16291241
TI  - Fluorescence resonance energy transfer-based assays for the real-time detection
      of nitric oxide signaling.
AB  - Low-molecular-weight S-nitrosothiols are found in many tissues and affect an
      array of signaling pathways via decomposition to *NO or exchange of their -NO
      function with thiol-containing proteins (transnitrosation). We used spectral
      laser scanning confocal imaging to visualize the effects of the membrane permeant
      S-nitrosothiol, S-nitrosocysteine ethyl ester (SNCEE), on a fluorescence
      resonance energy transfer (FRET) reporter based on the cysteine-rich heavy metal
      binding protein, metallothionein (FRET-MT) flanked by enhanced cyan and yellow
      fluorescent proteins (ECFP and EYFP, respectively). We previously showed that
      FRET can be used to follow metal binding and release by this construct. SNCEE (50
      microM) induced a decrease in energy transfer, as shown by an increase in the
      peak emission intensity of the donor fluorophore (ECFP) and a decrease in that of
      the acceptor (EYFP). These changes in intramolecular FRET were reversed by 50
      microM dithiothreitol (DTT), suggesting nitrosothiol-mediated modification of a
      cysteine residue in MT. Furthermore, the effects of SNCEE on the FRET-MT reporter
      were not affected by HbO(2), which would be expected to block any process
      involving (*)NO liberated by decomposition of nitrosothiol but would not
      necessarily affect transnitrosation. In further support of SNCEE-induced
      conformational changes in MT, we used live cell imaging of the zinc-sensitive
      fluorescent indicator FluoZin-3 to show that SNCEE also caused increases in
      labile Zn(2+).

PMID- 16291242
TI  - Nitric oxide is a signaling molecule that regulates gene expression.
AB  - Nitric oxide (NO) is a dynamic and bioreactive molecule that can both participate
      in and inhibit the genesis of disease. Its ability to have an impact on a wide
      range of physiological events stems from its capacity to reversibly alter the
      expression of specific genes and the activities of a wide range of proteins and
      signaling pathways. Yet, NO* remains an enigmatic molecule. Recently developed
      technologies, including gene-chips, two-dimensional electrophoresis, RNA
      interference, matrix-assisted laser desorption ionization (MALDI)-TOF (time-of
      flight) mass spectrometry, and protein arrays will allow us to better understand
      how NO* and associated reactive nitrogen species (RNS) regulate both physiology
      and disease states, toward the development of treatments using NO* synthase
      inhibitors or NO* donors.

PMID- 16291243
TI  - NO signaling in ARE-mediated gene expression.
AB  - Nitric oxide (NO) and peroxynitrite, which serve as cell signal molecules,
      activate the antioxidant response element (ARE) for the induction of phase II
      antioxidant enzymes as an adaptive response. The reactive nitrogen species plays
      an essential role in Nrf2 activation and Nrf2 binding to the ARE present in the
      target genes. In this chapter, we describe the system by which the NO signaling
      pathway regulates ARE-mediated gene expression, which includes immunochemical
      assessment and gel shift analysis of Nrf2 activation.

PMID- 16291244
TI  - Tyrosine phosphorylation in nitric oxide-mediated signaling events.
AB  - In this chapter, we provide an overview of nitric oxide (NO)-tyrosine
      phosphorylation signal transduction pathways, integrating them with the cyclic
      guanosine monophosphate (cGMP) and S-nitrosylation-mediated pathways that are
      triggered by NO. The second half of this chapter includes a description of the
      methods that our laboratory has used extensively to characterize the mechanisms
      involved in signaling events mediated by this pathway. These include assays for
      detecting protein tyrosine phosphorylation, tyrosine phosphorylation of the
      epidermal growth factor (EGF) receptor, phosphorylation of the ERK1/2 mitogen
      activated protein (MAP) kinases, transfection of cells with modified forms of
      p21Ras, and an assay of p21Ras.

PMID- 16291245
TI  - Identification and evaluation of NO-regulated genes by differential analysis of
      primary cDNA library expression (DAzLE).
AB  - Nitric oxide (NO) has numerous physiological roles in the cell. One of the
      actions of NO is gene regulation through protein modification and signal
      transduction. In neurons, NO can be produced from neuronal NO synthase, which is
      activated by calcium following N-methyl-D-aspartate (NMDA) receptor activation.
      Differential analysis of cDNA library expression (DAzLE) was used to identify
      differentially expressed genes by NO. Fundamentally, this technique combines
      differential hybridization to isolate genes whose expression is differentially
      regulated with microarray to analyze the expression of the isolated genes. The
      expression of genes identified by the DAzLE method is verified further by
      quantitative real-time polymerase chain reaction (RT-PCR) and/or Northern blot
      analysis. The high selectivity and sensitivity of this technique for detecting
      differentially expressed gene transcripts enable the investigation and
      identification of a panel of genes that are regulated by NO.

PMID- 16291246
TI  - Role of NO in enhancing the expression of HO-1 in LPS-stimulated macrophages.
AB  - Macrophages serve as the first-line defense against invading pathogens by (a)
      overproducing O2- via activation of NADPH-oxidase localized in its plasma
      membrane, (b) inducing the expression of inducible nitric oxide synthase (iNOS)
      and overproducing NO, and (c) generating highly toxic peroxynitrite (ONOO-) to
      kill the invading pathogens without killing the macrophages themselves. Results
      show that this was due at least in part to the NO-derived induction of heme
      oxygenase-1 (HO-1) expression. The NO-derived induction of HO-1 caused (a) rapid
      elimination of toxic heme to inhibit lipid peroxidation and to prevent further
      induction of iNOS, (b) rapid production of bile pigment antioxidants to scavenge
      reactive oxygen (O2-) and nitrogen (NO) metabolites, and (c) rapid production of
      carbon monoxide (CO) to inhibit further production of O2- and NO by blocking the
      activities of NADPH-oxidase and iNOS, respectively. Thus, the NO overproduced by
      the O2- -dependent induction of iNOS expression can scavenge O2- to produce ONOO
      , first to kill the invading pathogens and second to enhance the HO-1 expression
      in macrophages. This allows the survival of host tissues from the injuries caused
      by inflammatory oxidative stress.

PMID- 16291247
TI  - G-protein signaling in iNOS gene expression.
AB  - Heterotrimeric G proteins are the molecular switches in the receptor-mediated
      transmembrane signaling system. Inducible nitric oxide synthase (iNOS) is
      inducible by a variety of inflammatory stimuli, which leads to vascular
      hyporeactivity. In this chapter, the system to study the cell signaling pathways
      downstream of the GPCR coupling to G proteins is described for the study of iNOS
      gene expression. The cellular signaling pathways by which ligand induces iNOS may
      serve as the pharmacological targets for preventing or treating vascular
      hyporeactivity.

PMID- 16291248
TI  - Determination of nitric oxide-donor effects on tissue gene expression in vivo
      using low-density gene arrays.
AB  - Gene array technology has been used to examine gene expression changes following
      drug treatments, including administration of nitric oxide (NO) donors. High
      density arrays represent a powerful and popular method to analyze a large number
      of genes simultaneously. On the other hand, low-density arrays, available
      commercially at a lower cost, allow for the use of gene-specific primers, which
      reduces the risk of cross-hybridization among genes with similar sequence. For
      certain experiments in which the hypothesis is focused on a selected set of
      genes, use of low-density arrays might be more productive and cost-effective.
      Here, we describe our experience using low-density arrays to examine the effect
      of exposure to the NO-donor isobutyl nitrite on the expression of 23 cancer- and
      angiogenesis-related genes in mouse tissues. Detailed descriptions of data
      capture procedures, statistical tests, and confirmation studies using real-time
      quantitative (RTQ) reverse transcription polymerase chain reaction (RT-PCR) are
      presented. Three simple statistical methods, namely Student's t test, significant
      analysis of microarrays (SAM), and permutation adjusted t statistics (PATS), were
      applied on our gene array data, and their utilities were compared. All three
      methods yielded concordant results for the most significant genes, namely
      vascular endothelial growth factor (VEGF), VEGF receptor 3, Smad5, and Smad7. RT
      PCR confirmed VEGF upregulation as observed via gene arrays. PATS appeared to be
      more robust than SAM in handling our small gene array data set. This statistical
      method, therefore, appears more suited for analyzing low-density gene array data.
      We conclude that low-density gene array is a useful screening method that can be
      performed with lower cost and less cumbersome data treatment.

PMID- 16291250
TI  - Cytotoxic and cytoprotective actions of O2- and NO (ONOO-) are determined both by
      cellular GSH level and HO activity in macrophages.
AB  - Survival of macrophages, which serve as the first-line defense against invading
      pathogens by invoking the overproduction of highly toxic peroxynitrite (ONOO-),
      depends on their ability to maintain the intracellular GSH level and to induce
      the expression of heme oxygenase-1 (HO-1). The ONOO- is produced by macrophages
      stimulated by pathogens and is a powerful oxidant reacting directly with cellular
      GSH and proteins, killing both invading pathogens and macrophages themselves.
      However, macrophages can survive the toxicity of ONOO- by replenishing the
      depleted GSH level and by inducing HO-1 expression. In macrophages exposed to
      conditions overproducing O2-, NO, or ONOO-, the cellular level of GSH decreased
      rapidly, and when excessive, cells died. However, in cells surviving the toxicity
      caused by lower doses of O2-, NO, or ONOO-, the depleted intracellular GSH level
      was replenished, and HO-1 expression was increased, but not when they were
      coexposed to an inhibitor of HO-1 activity. Cells exposed to an inhibitor of GSH
      synthesis had greater induction of HO-1 expression and survived. However, cells
      exposed to an inhibitor of HO-1 activity died extensively and could not be
      revived by addition of N-acetylcysteine (NAC), a precursor of GSH synthesis.
      Thus, the dichotomous cytotoxic or cytoprotective effects of O2-, NO, or ONOO- in
      macrophages are determined both by cellular GSH level and by HO-1 activity.

PMID- 16291249
TI  - Cell H2O2 steady-state concentration and mitochondrial nitric oxide.
AB  - For many years, mitochondrial respiration was thought to follow an "all or
      nothing" paradigm supporting the notion that in the normal O2 concentration
      range, respiration is mainly controlled by tissue demands. However, nitric oxide
      produced by cytosol or mitochondrial nitric oxide synthases adapts respiration to
      different physiologic conditions and increases the mitochondrial production of O2
      active species that contributes to NO clearance. Because mitochondrial NO
      utilization is sensitive to environmental or hormonal modulation, and because
      diffusible active species, like H2O2, are able to regulate genes related to
      proliferation, quiescence, and death, we surmised that the two mechanisms
      converge to elicit the different responses in cell physiology.

PMID- 16291252
TI  - Functional activity of mitochondrial nitric oxide synthase.
AB  - The functional activity of mitochondrial nitric oxide synthase (mtNOS) is
      determined by inhibiting O2 uptake and by enhancing H2O2 production. The effect
      of mtNOS activity on mitochondrial O2 uptake is assayed in state 3 respiration in
      two limit conditions of intramitochondrial NO: at its maximal and minimal levels.
      The first condition is achieved by supplementation with L-arginine and superoxide
      dismutase (SOD), and the second by addition of an NOS inhibitor and
      oxyhemoglobin. The difference between state 3 O2 uptake in both conditions
      constitutes the mtNOS functional activity in the inhibition of cytochrome oxidase
      activity. The functional activity of mtNOS in enhancing mitochondrial H2O2
      generation in state 4 is given by the NO inhibition of ubiquinol-cytochrome c
      reductase activity. Simple determinations with the oxygen electrode or the
      measurement of mitochondrial H2O2 production can be used to assay the effects of
      physiological and pharmacological treatments on mtNOS activity.

PMID- 16291251
TI  - Determination of mitochondrial nitric oxide synthase activity.
AB  - The main biological targets of nitric oxide (NO) are hemoproteins, thiols, and
      superoxide anion (O2-). Mitochondria possess several hemoproteins, thiol
      containing molecules, and they are one of the prime cellular producers of O2-.
      Thus, these organelles remain one of the main biological targets for NO. Reports
      on the existence of a Ca2+-sensitive mitochondrial NO synthase (mtNOS) have
      opened a new window in the field of NO and mitochondria research (Ghafourifar and
      Richter, 1997). mtNOS-derived NO reversibly decreases the activity of the
      mitochondrial hemoprotein, cytochrome c oxidase. This function of mtNOS regulates
      mitochondrial respiration and transmembrane potential (Deltapsi). The NO
      generated by mtNOS reacts with mitochondrial thiol-containing proteins including
      caspase-3. Because the S-nitrosated caspase-3 remains apoptotically silent as
      long as it is located within the mitochondria, this function of mtNOS portrays an
      anti-apoptotic property for mtNOS. mtNOS-derived NO also reacts with O2- to
      generate peroxynitrite. mtNOS-derived peroxynitrite induces oxidative stress and
      releases cytochrome c from the mitochondria, which represents a pro-apoptotic
      role for mtNOS. How mitochondria harmonize the reversible functions of mtNOS for
      mitochondrial respiration, its anti-apoptotic actions via S-nitrosation of
      caspase-3, versus the pro-apoptotic properties of peroxynitrite remains to be
      fully understood. However, intramitochondrial ionized Ca2+ concentration
      ([Ca2+]m) and the status of mitochondrial reducing defense barriers seem to play
      crucial roles in orchestrating the functions of mtNOS for mitochondria and cells
      (Ghafourifar and Cadenas, 2005).

PMID- 16291253
TI  - Tetrahydrobiopterin as combined electron/proton donor in nitric oxide
      biosynthesis: cryogenic UV-Vis and EPR detection of reaction intermediates.
AB  - The role of tetrahydrobiopterin (BH4) as a cofactor in nitric oxide synthase
      (NOS) has been the object of intense research in the last few years. It was found
      that in addition to its established effects on the NOS heme spin state, substrate
      affinity, and enzyme dimerization, BH4 is required as a one-electron donor to
      oxyferrous [Fe(II).O2] heme that is formed as an intermediate in the catalytic
      cycle. Cryogenic spectroscopic techniques proved particularly useful in the
      identification of this role of BH4 in NO synthesis. With these methods, the
      mechanism of fast reactions, such as the reaction of ferrous NOS with O2, can be
      unraveled by lowering the reaction temperature to subzero values. This may not
      only reduce the rate to such an extent that the reaction can be followed on a
      time scale from seconds to minutes, but intermediates may be observed that do not
      accumulate at higher temperatures. Cryogenic ultraviolet-visible (UV-vis) and
      electron paramagnetic resonance spectroscopy have been applied to clarify why the
      BH4 analogue 4-amino-tetrahydrobiopterin (4-amino-BH4) is unable to support NO
      synthesis. In the course of these studies, evidence was gathered supporting a
      role for BH4 as an obligate proton and electron donor. It is believed that the
      inhibitory action of 4-amino-BH4 derives from an inability to serve as a proton
      donor, even though it is perfectly able to serve as an electron donor. In this
      chapter, the suitability, drawbacks, and advantages of cryogenic methods are
      discussed.

PMID- 16291254
TI  - Antisense-mediated knockdown of iNOS expression in the presence of cytokines.
AB  - The impact of nitric oxide (NO) synthesized after activation by proinflammatory
      cytokines and/or bacterial products by an inducible NO synthase (iNOS) is still
      contradictory. Various methods to inhibit iNOS expression or activity have been
      established. A relatively new approach to inhibit iNOS-derived NO production is
      the antisense (AS) technique, which theoretically provides a specific and
      efficient method for inhibiting gene expression and function. This chapter
      focuses on the application of iNOS-specific AS-oligodeoxynucleotide (ODN) and
      highlights some of the pitfalls that must be considered to use this technique
      effectively.

PMID- 16291255
TI  - Soluble guanylyl cyclase: the nitric oxide receptor.
AB  - Soluble guanylyl cyclase is recognized as the most sensitive physiologic receptor
      for nitric oxide. Binding of nitric oxide to the heme moiety of the cyclase
      induces its capacity to synthesize the second messenger cGMP. Although the
      changes in the state of the heme moiety upon exposure of enzyme to NO and its
      correlation to the stimulation of sGC catalytic activity are well documented, the
      exact mechanism of such coupling is not understood. Structure-functional studies
      are required to elucidate this process. In this chapter, we describe the method
      of expression and purification of recombinant human alpha1/beta1 isoform of sGC
      in insect cells, which can be a useful tool for such studies. Several approaches
      that enable characterization of the binding of NO to sGC heme moiety are also
      described.

PMID- 16291256
TI  - Purification and characterization of NO-sensitive guanylyl cyclase.
AB  - Nitric oxide (NO)-sensitive guanylyl cyclase (GC) represents the receptor for the
      signaling molecule NO in mammals. The enzyme consists of two different subunits
      and contains a prosthetic heme group acting as an NO acceptor. Binding of NO to
      the heme accelerates the catalytic conversion from guanosine triphosphate (GTP)
      to cyclic guanosine monophosphate (cGMP) by 2.0-2.5 orders of magnitude. NO
      sensitive GC represents a well-established drug target because the NO-releasing
      drugs used in the therapy of coronary heart disease act by stimulation of the
      enzyme. Furthermore, new NO-independent GC activators are under development.
      Characterization of the molecular mechanisms by which NO-releasing and NO
      independent drugs control enzyme activity often requires very large amounts of
      enzyme, as do attempts to resolve the structure of GC. Because heterologous
      expression systems turned out to yield only small amounts of the enzyme, the
      purification from bovine lungs is still a convenient way to obtain the enzyme in
      large quantities. In this chapter, a fast method for purification of the enzyme
      from bovine lungs is described, and basic methods for characterization of the
      enzyme are summarized.

PMID- 16291257
TI  - The measurement of nitric oxide production by cultured endothelial cells.
AB  - Nitric oxide (NO) produced by vascular endothelial cells (ECs) plays a critical
      role in normal vascular physiology. Important insights into mechanisms regulating
      the production of endothelial NO have been derived from in vitro studies
      employing cultured ECs. Although many techniques for the detection of NO have
      been described, many of these methods lack adequate sensitivity to detect the
      small amount of NO produced by cultured ECs. In this chapter, we describe three
      protocols that employ chemiluminescence, electron spin resonance, or
      electrochemical techniques to permit the reliable detection of EC NO production.

PMID- 16291258
TI  - Use of microdialysis to study interstitial nitric oxide and other reactive oxygen
      and nitrogen species in skeletal muscle.
AB  - Microdialysis techniques can be used to sample the interstitial space of tissues
      such as skeletal muscle. Analytical developments have allowed adaptations of
      these techniques to permit continuous monitoring of nitric oxide and a number of
      other reactive oxygen and nitrogen species in skeletal muscle extracellular
      space. Methods are described for assessment of interstitial nitrate and nitrite
      content, superoxide anion content, hydroxyl radical activity, and the content of
      relatively stable lipid radicals detectable using spin trapping and electron spin
      resonance techniques in skeletal muscle of rodents at rest and during contractile
      activity.

PMID- 16291259
TI  - Nitric oxide, proteasomal function, and iron homeostasis--implications in aging
      and neurodegenerative diseases.
AB  - In this chapter, oxidant-induced transferrin receptor-mediated iron-signaling and
      apoptosis are described in endothelial and neuronal cells exposed to oxidants.
      The role of nitric oxide in the regulation of iron homeostasis and oxidant
      induced apoptosis is described. The interrelationship between oxidative stress,
      iron-signaling, and nitric oxide-dependent proteasomal function provides a
      rational mechanism that connects both oxidative and nitrative modifications.

PMID- 16291260
TI  - Nitric oxide production by primary liver cells isolated from amino acid diet-fed
      rats.
AB  - Primary mixed liver cells were isolated from rats that had been fed an amino acid
      (AA) diet in which natural protein was replaced with a defined mixture of pure
      AAs. Nitric oxide (NO) production from these cells in vitro was monitored using a
      nitric oxide (NO)-selective fluorescent probe, diaminofluorescein, followed by
      flow cytometric analysis. High levels of NO fluorescence were seen in
      approximately half of liver cells isolated from rats fed an AA diet for 1-7 days,
      whereas there was baseline fluorescence in cells obtained from regular diet-fed
      rats. The apparent size of NO-producing cells was smaller than those not
      producing NO. The production of NO was inhibited when rats were treated with
      either inducible NO synthase (iNOS)- or endothelial NOS-specific inhibitor, and
      an inhibitor for iNOS induction during AA diet feeding. L-arginine or L-glutamine
      (material for L-arginine biosynthesis) enriched diet showed the same NO
      augmentation as in AA diet. It is speculated that a high content of free L
      arginine in AA diet may have caused enhanced NO production.

PMID- 16291262
TI  - Assessing NO-dependent vasodilatation using vessel bioassays at defined oxygen
      tensions.
AB  - Results from vessel bioassays have provided the foundation for much of our
      understanding of the mechanisms that control vascular homeostasis and blood flow.
      The seminal observations that led to the discovery that nitric oxide (NO) is a
      critical mediator of vascular relaxation were made with the use of such
      methodology, and many studies have used NO-dependent vessel relaxation as an
      experimental readout for understanding mechanisms that regulate vascular NO
      function. Studies have coupled controlling oxygen tensions within vessel bioassay
      chambers to begin to understand how oxygen-specifically hypoxia-regulate NO
      function, and this context has identified red cells-specifically hemoglobin
      within-as critical modulators. Alone, vessel bioassays or measuring oxygen
      partial pressures (pO2) is relatively straightforward, but the combination
      necessitates consideration of several factors. We use the example of deoxygenated
      red cells/hemoglobin-dependent potentiation of nitrite-dependent dilation to
      illustrate the salient factors that are critical to consider in designing and
      interpreting experiments aimed at understanding the interplay between oxygen and
      NO function in the vasculature.

PMID- 16291261
TI  - Update on nitric oxide-dependent vasodilation in human subjects.
AB  - There currently is great interest in translating findings about the importance of
      nitric oxide (NO) in vascular biology to the clinical arena. The bioactivity of
      endothelium-derived NO can readily be assessed in human subjects as vasodilation
      of conduit arteries or increased flow, which reflects vasodilation of resistance
      vessels. This chapter provides an update on the available noninvasive methodology
      to assess endothelium-dependent vasodilation in human subjects.

PMID- 16291263
TI  - Nonenzymatic nitric oxide formation during UVA irradiation of human skin:
      experimental setups and ways to measure.
AB  - Many of the local ultraviolet (UV)-induced responses, including erythema and
      edema formation, inflammation, premature aging, and immune suppression, can be
      influenced by nitric oxide synthase (NOS)-produced NO, which plays a pivotal role
      in cutaneous physiology. Besides enzyme-mediated NO production, UV radiation
      triggers an enzyme-independent NO formation in human skin. This occurs due to
      decomposition of photoreactive nitrogen oxides like nitrite and S-nitrosothiols,
      which are present in human skin at relatively high concentrations and lead to
      high-output formation of bioactive NO. This enzyme-independent NO formation opens
      a new field in cutaneous physiology and will extend our understanding of
      mechanisms contributing to skin aging, inflammation, and cancerogenesis but also
      functional protection. Therefore, it is of high interest to examine the chemical
      storage forms of these potential NO-generating agents in skin, the mechanisms and
      kinetics of their decomposition, and their biological relevance.

PMID- 16291264
TI  - Nitric oxide and cell signaling: in vivo evaluation of NO-dependent apoptosis by
      MRI and not NMR techniques.
AB  - Apoptosis plays a key role in many pathological circumstances, such as
      neurodegenerative diseases. In these processes, the involvement of nitric oxide
      (NO) has been well established, and the ability of NO to exert cellular damage
      due to its reactive oxidative properties is perhaps the primary neurotoxic
      mechanism. The caspase 3 activation has recently been observed in stroke, spinal
      cord trauma, head injury, and Alzheimer's disease. Although numerous techniques
      have been described to evaluate apoptosis, these approaches involve invasive
      techniques and cannot provide detailed information about apoptosis in vivo. In
      this chapter, we describe the use of functional magnetic resonance imaging (fMRI)
      as a non-invasive technique to detect apoptosis in vivo. fMRI techniques can
      detect apoptosis at early stages in the process, allowing the onset in intact
      biological systems, providing a useful tool for monitoring apoptosis progression.

PMID- 16291265
TI  - Microelectrode for in vivo real-time detection of NO.
AB  - Nitric oxide (NO) is gaining importance with its diverse spectrum of clinic
      effects. However, there is still a need for an ideal sensor to monitor its
      concentration in tissue. An ideal sensor should not interfere with the ongoing
      physiological process, while making fast, reliable, and repeatable measurements.
      We have designed a microelectrode for electrochemical NO measurement from tissue
      with relatively low interference and reliable results upon calibration. Details
      of electrode preparation and calibration procedure are explained along with an
      experiment to monitor effects of photodynamic therapy.

PMID- 16291266
TI  - Real-time detection of nitric oxide isotopes in lung function tests.
AB  - In lung function tests, the determination of the pulmonary diffusing capacity (D)
      using the single-breath method is a commonly applied technique. The calculation
      of D is performed on the basis of accurate measurements of indicator gas
      concentrations. In this chapter, we demonstrate the appropriateness of the stable
      nitric oxide (NO) isotopes 14NO and 15NO in revealing reliable data of D. We
      performed studies on animals (14NO) by using respiratory mass spectrometry (M3)
      and on humans (15NO) by applying laser magnetic resonance spectroscopy (LMRS).
      The equipment was characterized by sufficient detection limits of 70
      parts/billion at [14NO] = 0.001% (M3) and 40 parts/billion at [15NO] = 0.002 %
      (LMRS), respectively. Lastly, we were able to show that D-values for 14NO indeed
      reveal the entire diffusive properties of the alveolar-capillary membrane and
      that 15NO is a useful indicator gas for reflecting disturbances of pulmonary gas
      exchange.

PMID- 16291267
TI  - ESR techniques for the detection of nitric oxide in vivo and in tissues.
AB  - Plasma levels of nitrite/nitrate may not accurately reflect endothelial nitric
      oxide synthase (eNOS) function because of interference by dietary nitrates.
      Nitrosyl hemoglobin (HbNO), a metabolic product of nitric oxide (NO*), may better
      correlate with bioavailable NO*, but it may depend on the activity of different
      NOS isoforms and may be affected by dietary nitrite/nitrate. This work examined
      the correlation between vascular endothelial NO* release and blood levels of
      HbNO. We measured HbNO in mouse blood using electron spin resonance (ESR)
      spectrometry, and we quantified vascular production of NO* using colloid
      Fe(DETC)2 and ESR. C57Blk/6 mice who were fed a high-nitrate diet had levels of
      plasma HbNO increased 10-fold, whereas those fed a low-nitrate diet had decreased
      HbNO levels from 0.58 +/- 0.02 to 0.48 +/- 0.01 microM. Therefore, a low-nitrate
      diet is essential when using HbNO as a marker of eNOS activity. Treatment with L
      NAME and the eNOS-specific inhibitor L-NIO halved HbNO formation, which reflects
      the complete inhibition of NO* release by aorta endothelium. Treatment of mice
      with the selective inducible NOS (iNOS) inhibitor, 1400W, or the selective
      neuronal NOS (nNOS) inhibitor N-AANG did not alter either blood HbNO levels or
      vascular NO*. The relationship between HbNO and NO* production by the endothelium
      (0.23 microM HbNO to 5.27 microM/h of NO*/mg of dry weight aorta) was found to be
      identical for both C57Blk/6 mice and mice with vascular smooth muscle-targeted
      expression of p22phox associated with strong increase in eNOS activity. These
      results support the important role of eNOS in the formation of circulating HbNO,
      whereas iNOS and nNOS do not contribute to HbNO formation under normal
      conditions. These data suggest that HbNO can be used as a noninvasive marker of
      endothelial NO* production in vivo.

PMID- 16291268
TI  - A novel cause of invasive pulmonary infection in an immunocompetent patient:
      Aspergillus candidus.
AB  - Aspergillus candidus, a common contaminant of grain dust, may represent an
      important respiratory hazard to grain workers, considering its immunomodulating
      capability by producing p-terphenyl metabolites and terprenins, potent cytotoxic
      substances. However, there are only three cases of A. candidus infection in the
      English literature, one fatal solitary brain mass and two onychomycosis. We
      describe the first case of invasive pulmonary infection and skin abscesses due to
      A. candidus, determination of minimal inhibitory concentration for anti-fungals,
      and the successful treatment with liposomal amphotericin B and itraconazole.
      Possible mechanisms involved in the dissemination of infection in an
      immunocompetent host are discussed.

PMID- 16291269
TI  - Pseudomonas aeruginosa infective endocarditis presenting as bacterial meningitis.
AB  - Pseudomonas aeruginosa is a rare cause of infective endocarditis. The case of
      community-acquired P. aeruginosa infective endocarditis reported here is the
      first described in the literature to present as bacterial meningitis.
      Furthermore, new risk factors for P. aeruginosa infective endocarditis, including
      mitral annular calcification and re-use of insulin syringes, are proposed.
      Treatment of P. aeruginosa infective endocarditis complicated by bacterial
      meningitis is discussed.

PMID- 16291270
TI  - Successful antibiotic treatment of Borreliosis associated pseudolymphomatous
      systemic infiltrates.
AB  - The clinical management of late stage Borreliosis can be difficult due to various
      associated symptoms and signs and cumbersome microbiological tests. We report a
      case of successful antibiotic treatment of Borreliosis-associated
      pseudolymphomatous infiltrates in bone marrow and lymph nodes, which were
      diagnosed by bone marrow trephine biopsy and positron emission tomography.

PMID- 16291271
TI  - Clindamycin in the treatment of group G beta-haemolytic streptococcal infections.
AB  - We report a case of severe streptococcal cellulitis in a healthy 47 year old
      male, where the sole microbial isolate was a beta-haemolytic group G
      Streptococcus. Treatment failure with high dose penicillin was observed despite
      in vitro sensitivity. The addition of clindamycin resulted in dramatic clinical
      improvement. This may indicate an Eagle-type effect (whereby antibiotics exhibit
      paradoxically reduced bactericidal activities at high drug concentrations), in
      group G beta-haemolytic infections. Although well documented with group A
      streptococcal infections, this phenomenon has not been fully recognised with
      group G beta-haemolytic streptococcal infections. This may have important
      implications for clinical management.

PMID- 16291272
TI  - Successful treatment of MRSA native valve endocarditis with oral linezolid
      therapy: a case report.
AB  - Staphylococcal endocarditis is potentially fatal and is now the most common cause
      of infective endocarditis with a mortality rate of 25-47% [Hecht SR, Berger M.
      Right-sided endocarditis in intravenous drug users: prognostic features in 102
      episodes. Ann Intern Med 1992;117:560-6]. Its treatment requires maintenance of
      bactericidal level of antibiotics for prolonged periods to attain a culture
      negative state. Although intravenous vancomycin is currently the drug of choice
      for methicillin resistant Staphylococcus aureus (MRSA) endocarditis, we present a
      case treated successfully with oral linezolid for 4 weeks due to a lack of venous
      access.

PMID- 16291273
TI  - Herpes simplex virus type 2 recurrent meningitis (Mollaret's meningitis): a
      consideration for the recurrent pathogenesis.
AB  - We report a 44-year-old Japanese woman with herpes simplex virus (HSV) type 2
      recurrent meningitis (Mollaret's meningitis). The diagnosis was confirmed by
      nested polymerase chain reaction in her cerebrospinal fluid, but the patient's
      conventional HSV antibodies by complement fixation, neutralizing test or enzyme
      immunoassay showed low titres with low lymphoproliferative response. Several
      similar cases are discussed. Although the reason for the recurrent pathogenesis
      is uncertain, our report suggests that the low immune response including immune
      evasion may be involved in the pathogenesis of HSV type 2 recurrent meningitis.
      For this patient, long-term suppressive and patient-initiated therapies were
      conducted to prevent the recurrence of meningitis.

PMID- 16291274
TI  - Lumbar drainage for control of raised cerebrospinal fluid pressure in
      cryptococcal meningitis: case report and review.
AB  - Raised intracranial pressure in the absence of ventricular dilatation is common
      in cryptococcal meningitis and associated with increased mortality. We report the
      case of a patient with HIV-associated cryptococcal meningitis, who developed
      increasing CSF pressure and visual impairment on therapy despite serial lumbar
      punctures. Insertion of a temporary lumbar drain controlled the opening pressure
      and resulted in full visual recovery. The advantages and necessary precautions
      with this approach are reviewed, and alternative protocols for the use of lumbar
      drains discussed.

PMID- 16291275
TI  - Voriconazole-resistant disseminated Paecilomyces variotii infection in a
      neutropenic patient with leukaemia on voriconazole prophylaxis.
AB  - Paecilomyces variotii, an emerging hyalohyphomycetes, has been reported to be
      susceptible in vitro to voriconazole. We describe a case of disseminated P.
      variotii infection in a neutropenic child with relapsed leukaemia who was on
      voriconazole prophylaxis. The P. variotii isolate was resistant to voriconazole
      in vitro. The patient responded to liposomal amphotericin B.

PMID- 16291276
TI  - Endocarditis caused by Propionibacterium acnes: an easily ignored pathogen.
AB  - Propionibacterium acnes, which usually considered as a contaminant, has been
      found to be an emerging pathogen in human diseases. We describe a case of
      prosthetic valve related endocarditis caused by P. acnes. Sequencing of the
      genetic coding of 16S ribosomal RNA was used to identify the pathogen and random
      amplified polymorphic DNA patterns further confirmed the persistent bacteraemia,
      which help to determine the diagnosis.

PMID- 16291277
TI  - Intracerebral CSF collection mimicking cerebral abscess in a patient suffering
      from cryptococcal meningitis.
AB  - We report a case of a large intracerebral CSF collection formed along the course
      of the catheter of an ommaya-type reservoir (Medtronic 12 mm), implanted in a
      patient suffered from cryptococcal meningitis in the frame of CLL. This
      collection was at first diagnosed as intracerebral abscess but emergency
      craniotomy proves clear CSF collection with no signs of infection. We describe
      the case and we discuss the issue of CSF pressure pathophysiology and changes in
      flow dynamics, to patients with cryptococcal meningitis.

PMID- 16291278
TI  - Isolation of measles virus from middle ear fluid of infants with acute otitis
      media.
AB  - Measles virus was isolated from the middle ear fluid (MEF) of two infant cases of
      acute otitis media (AOM) associated with measles. This is the first report on the
      isolation of measles virus from the MEF in patients with AOM, and possibility of
      the measles virus as a causative agent of AOM was suggested.

PMID- 16291279
TI  - Community-acquired MRSA bacteremic necrotizing pneumonia in a patient with
      scrotal ulceration.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is being recognized
      increasingly as a cause of community-acquired infection. The organism usually
      causes skin and soft tissue infection. Here, we present a patient with community
      acquired MRSA pneumonia and review the literature. The patient, a 37-year-old
      Saudi male with no significant medical history was admitted with fever,
      respiratory distress and scrotal ulceration. Scrotal swabs and blood cultures
      grew MRSA. Imaging studies showed necrotizing pneumonia. Physical examination and
      echocardiographic findings revealed no evidence of endocarditis. The patient was
      treated successfully with 4 weeks of intravenous vancomycin. The infection
      appears to have originated in the skin and subcutaneous tissues of the scrotum,
      and subsequently led to necrotizing pneumonia. Community-acquired MRSA pneumonia
      has been associated with the production of Panton-Valentine leukocidin.

PMID- 16291280
TI  - Serum neopterin levels in patients with brucellosis.
AB  - OBJECTIVES: The aim of this study was to evaluate the importance of neopterin
      levels in brucellosis and its alterations with treatment. METHODS: Thirty
      patients who had positive clinical findings, Brucella standard tube agglutination
      tests and/or positive blood culture were included in the study. The control group
      was composed of 30 healthy subjects. Neopterin (NPT) levels were measured by
      ELISA according to the protocol of manufacturer. RESULTS: Mean NPT levels were
      54.15+/-33.7 nmol/l in study groups and 8.75+/-2.48 nmol/l in controls (P<0.001).
      It was determined that NPT levels measured at the time of admission of the
      patients had a linear correlation between the duration of complaint (r=0.560,
      P=0.001). While the mean NPT levels in patients with complaints of over 30 days
      were 79.07+/-34.9 nmol/l and it was 39.71+/-23.4 nmol/l in the patients with
      complaints of less than or equal to 30 days (P=0.002). NPT values measured after
      treatment (20.48+/-25.6) was determined lower by statistical means than the
      values measured before treatment (54.15+/-33.7, P=0.0001). The NPT levels of
      patients with positive blood culture (75.56+/-33.6) were higher than those of
      with negative blood cultures (32.72+/-15.2, P=0.001). CONCLUSION: It was
      concluded that the NPT levels were higher in patients with brucellosis. In
      addition, it was found that the levels of NPT were higher in non-responding
      patients than responded to the brucellosis treatment. It was thought that
      monitoring NPT levels could be useful for the extent and activity of the disease.

PMID- 16291281
TI  - Dengue infection during pregnancy and transplacental antibody transfer in Thai
      mothers.
AB  - OBJECTIVES: The objectives of this study were to estimate dengue seroprevalence
      in a population of Thai pregnant women, living in a highly endemic area and
      placental transfer of dengue antibodies. METHODS: A cross-sectional
      seroprevalence study of 245 pregnant women at delivery. RESULTS: Dengue HAI
      antibodies were positive in 94.7%. Maternal age was the only risk factor
      associated with dengue infection as older mothers (>20 years) were significantly
      more likely to be seropositive than younger women (p<0.0001). Cord antibody
      titres varied with maternal age and antibody titre, were significantly higher in
      babies born to younger mothers (<20 years) (p=0.01), and were significantly
      correlated with maternal titre. Low birthweight babies had lower transfer ratios
      for DEN-2 antibody (1.06) compared to heavier babies (1.36, p=0.05). No mother or
      neonate had dengue IgM detected. Two women were classified as recently, but not
      currently infected with dengue virus and we consider it likely these were first
      trimester infections. As no infant became infected the fetal infection was 0%.
      CONCLUSIONS: Younger mothers were more likely to have been recently infected,
      resulting in higher antibody titres. Maternal dengue antibody transfer was
      proportional to maternal antibody concentration.

PMID- 16291282
TI  - Comparative efficacy of Rubini, Jeryl-Lynn and Urabe mumps vaccine in an Asian
      population.
AB  - OBJECTIVE: The comparative efficacy of the three mumps vaccine strains (Jeryl
      Lynn, Urabe and Rubini) was conducted in an Asian population from data arising
      from an epidemiological investigation of seven institutional outbreaks of mumps
      in Singapore. METHODS: Demographic information (gender, age, ethnic group),
      clinical presentation and vaccination history (date and place of mumps
      vaccination, type of mumps vaccine received) of all children who attended the six
      childcare centres and one primary school where outbreaks of 20 or more cases of
      mumps occurred in 1999 were collected. The attack rate of the unvaccinated group
      and the attack rates of the vaccine groups (for each vaccine strain) were
      determined and the vaccine efficacy of the three vaccines calculated. RESULTS:
      The vaccine efficacy of the Jeryl-Lynn strain, Urabe strain and Rubini strain
      mumps vaccine were 80.7, 54.4 and -55.3%, respectively. CONCLUSION: Rubini strain
      mumps vaccine conferred no protection and has since been deregistered in
      Singapore.

PMID- 16291283
TI  - Growth, morbidity and mortality after chickenpox infection in young children in
      Guinea-Bissau.
AB  - OBJECTIVE: To examine whether chickenpox in children below 2 years of age is
      associated with post-infection changes in growth, morbidity or mortality.
      METHODS: An outbreak of chickenpox was investigated in Guinea-Bissau. An
      examination, interview and anthropometry were performed 6 months after the
      epidemic for a group of children and matched controls whose weight had been
      measured at the time of the chickenpox episode. All children diagnosed with
      chickenpox before 2 years of age were followed for survival and hospitalisations
      to the age of 3 years and compared with all other children in the community.
      RESULTS: At the 6-month follow-up, skin infections tended to be more frequent in
      cases (p<0.06) and more cases had used antibiotics within the last month
      (p<0.03). Although there had been no difference before chickenpox infection,
      girls with chickenpox infection had significantly higher weight, height and
      larger arm-circumferences than controls (all p<0.01). After chickenpox infection,
      the incidence of hospitalisation and long-term mortality was the same for cases
      and other children in the community (respectively, incidence rate ratio=1.16
      (0.77-1.74) and mortality ratio=0.74 (0.39-1.41)). CONCLUSION: Though chickenpox
      may be associated with increased short-term morbidity, it does not appear to have
      any negative long-term effect on growth, severe morbidity and survival of young
      children.

PMID- 16291284
TI  - Responsiveness to interferon alpha in chronic hepatitis B by presumed vertical
      transmission.
AB  - This study was to evaluate responsiveness to IFN-alpha and investigate the
      benefits of sustained response (SR) in patients who were presumed as being
      vertically transmitted in Korea. A total of 46 patients of presumed vertical
      transmission with biopsy-proven HBeAg-positive chronic HBV infection were treated
      with IFN-alpha and followed. We tried to find the factors associated with SR and
      compared the cumulative rate of HCC and survival between SR group and non
      sustained/non-responder (NSR) group. HBeAg loss was acquired in 35% (16/46)
      within a year but SR was observed in 22% (10/46). Age <35 years and ALT levels
      >7xULN were significant favorable factors for SR (OR 0.56, 0.49, 95%CI 0.38-0.82,
      0.29-0.81, respectively) (both P<0.05). There were no significant differences of
      cumulative HCC-free survival (100 vs. 68% at 12 years, P=0.36) and survival (100
      vs. 73% at 12 years, P=0.3) between SR group and NSR group. In conclusion, age
      below 35 years old and serum ALT levels above 7xULN may predict IFN-alpha therapy
      induced SR among them, although we cannot affirm the effects on HCC prevention or
      survival.

PMID- 16291285
TI  - Abnormal production of transforming growth factor beta and interferon gamma by
      peripheral blood cells of patients with multidrug-resistant pulmonary
      tuberculosis in Brazil.
AB  - OBJECTIVES: The aim of the present study was to determine the immune response
      profile that differentiates patients with newly diagnosed (non-treated) pulmonary
      tuberculosis from multidrug-resistant (MDR) ones, as well as from healthy,
      tuberculin positive individuals. METHODS: Lymphocytes proliferative response to
      non-specific mitogen (PHA) and PPD were evaluated by 3H thymidine incorporation
      and cytokines were quantified using an ELISA assay. RESULTS: Patients with active
      disease showed a diminished proliferative response to PHA and PPD, while
      multidrug-resistant patients showed a diminished proliferative response to PHA,
      but a normal response to PPD. The cytokine production of newly diagnosed patients
      was characterized by a diminished production of IFNgamma and normal production of
      transforming growth factor (TGFbeta), while MDR patients revealed a normal
      production of IFNgamma accompanied by an increase in TGFbeta. CONCLUSIONS: The
      production of significant amounts of TGFbeta in MDR patients leads to a poor
      immune response and may contribute to the resistance of tuberculosis patients to
      drugs.

PMID- 16291286
TI  - Keratitis caused by Trachipleistophora anthropopthera.
AB  - We report a case of intrastromal keratitis in a 42-year-old male with underlying
      human immunodeficiency virus-1 infection. Numerous microsporidial spores were
      found from corneal biopsy. Ultrastructural studies of corneal tissues revealed
      dimorphic sporophorous vesicles containing characteristic spores belonging to
      Trachipleistophora anthropopthera. Infection could be controlled by penetrating
      keratoplasty but not by topical fumagillin and systemic albendazole per se. This
      is the first report of human keratitis caused by this organism.

PMID- 16291287
TI  - Campylobacter fetus bacteraemia in a healthy individual: clinical and
      therapeutical implications.
AB  - Campylobacter species are well-recognized common causes of gastrointestinal
      infections. While Campylobacter jejuni is probably the most common Campylobacter
      isolated in humans, Campylobacter fetus is rather infrequent and mostly related
      with bacteraemia. Even on such occasions, it seems that immunocompetent
      individuals are spared. We report a case of C. fetus bacteraemia in a healthy
      except for impaired fasting glucose (IFG) levels-farmer, presenting as an acute
      febrile syndrome and treated successfully as brucellosis.

PMID- 16291288
TI  - Acute bacterial meningitis in a patient receiving ibuprofen.
AB  - We report an atypical presentation of meningitis due to Neisseria meningitidis in
      a patient who received large doses of ibuprofen. Anti-inflammatory therapy such
      as NSAIDs could reduce CSF inflammation and modify the clinical outcome in
      patients with bacterial meningitis. However, the use of NSAIDs is not recommended
      in bacterial meningitis due to a lack of studies.

PMID- 16291289
TI  - Complications of the ethanol-lock technique in the treatment of central venous
      catheter sepsis.

PMID- 16291290
TI  - Acute respiratory failure due to Mycobacterium kansasii infection: immune
      reconstitution disease in a patient with AIDS.

PMID- 16291291
TI  - Measles during pregnancy including neonates.

PMID- 16291292
TI  - The CATIE schizophrenia effectiveness trial.

PMID- 16291293
TI  - Psycho-social factors and coping strategies as predictors of chronic evolution
      and quality of life in patients with low back pain: a prospective study.
AB  - Low back pain (LBP) is a major problem of public health. Chronic pain is the most
      difficult to treat and the most expensive. The way patients cope with their pain
      may influence its outcome. AIM: To identify coping strategies of LBP patients,
      and their influence on LBP evolution. METHODS: Ninety nine patients were assessed
      just after an acute LBP episode and one year later. Assessment tools included
      medical and social reports, scales of anxiety, depression, quality of life, locus
      of control (LOC), social support and coping strategies. RESULTS: One year after
      the initial episode, 67% of patients have improved and 33% had a chronic pain. A
      principal components analysis showed that two main dimensions might be identified
      inside the outcome: functional and emotional non-adjustment. Functional non
      adjustment was predicted by male gender, reduction of activity, and history of
      trauma over one year. Emotional non-adjustment was only predicted by trait
      depression. Reactions to pain were structured in four factors: distraction
      praying, helplessness-hopelessness, cognitive restructuration and perceived
      control. Two of these factors predicted adjustment one year later: distraction
      praying had a direct effect on functional non-adjustment, and helplessness
      hopelessness on emotional issue. CONCLUSIONS: Besides somatic factors,
      psychosocial predictors of LBP chronic evolution may be identified. Both aspects
      must be taken into account in order to prevent chronic pain. Perhaps cognitive
      behavior therapy may help LBP patients to cope with pain in a better way.

PMID- 16291294
TI  - Nurses' in the multi-professional pain team: a study of attitudes, beliefs and
      treatment endorsements.
AB  - BACKGROUND AND AIM: It is widely accepted that chronic pain is best treated by a
      multidisciplinary team. Team approaches are best facilitated if all members
      understand their own and each others role. Roles and responsibilities have
      inherent values and beliefs which need to be understood if the team is going to
      function optimally. Little is known about the attitudes and beliefs of the pain
      team or the individual professionals within it. All members of the pain team
      therefore need to critically examine the values and beliefs they bring to these
      teams. The aim of this study was to start this process for nurses. This was done
      uniquely by: finding out what components of pain management nurses endorse as
      important; investigating their beliefs about pain management; and exploring
      whether nurses' beliefs differ in relation to other service providers. METHOD:
      Data from 103 nurses was extracted from a wider research study of the congruence
      between what service providers and service users believe to be important
      treatments for chronic pain. Nurses were surveyed regarding their opinions about
      which specific treatments or treatment components they would endorse for people
      with chronic pain. Skevington's Beliefs About Pain Control Questionnaire (BPCQ)
      was also included. This measured beliefs in three crucial areas; the internal or
      personal control of pain, beliefs that powerful others (doctors) control pain and
      beliefs that pain is controlled by chance events. Statistical comparisons were
      made between nurses who endorsed particular treatments and their belief pattern.
      Differences between nurses and other professionals and service users were
      explored. RESULTS: The study showed that nurses were high treatment endorsers.
      There was universal agreement to the importance of 'The nurse', 'The
      multidisciplinary team', 'relaxation', and 'psychological assessment' for chronic
      pain management'. Nurses' endorsement patterns were different to the other
      professionals, because they endorsed more treatments. BPCQ scores were
      consistently lower than the other professionals and the service users.
      CONCLUSIONS: The findings of this study are congruent with emerging literature
      highlighting the complexity of health care. The high endorsement patterns seen in
      this study could be taken as support that nurses are, either tacitly or overtly,
      aware of this need to approach pain management in an open-minded and flexible
      manner.

PMID- 16291295
TI  - A comparison of the relative utility of coping and acceptance-based measures in a
      sample of chronic pain sufferers.
AB  - Previous research suggests that to define the problem of chronic pain as a
      problem of coping may not be as useful as framing it as a problem of acceptance
      for some patients. The coping approach may encourage, or at least permit, a
      somewhat inflexible agenda of pain reduction or control while the acceptance
      approach may allow a more flexible agenda of willingness to have pain in some
      circumstances where that serves the goal of better life functioning. The purpose
      of this study was to continue to examine the relative utility of concepts of
      coping and acceptance of pain. Two hundred and thirty consecutive patients
      seeking assessment from a pain management service were the participants in the
      study. Patients completed the Coping Strategies Questionnaire (CSQ) and the
      Chronic Pain Acceptance Questionnaire (CPAQ). A revised scoring method was used
      for the CSQ (to correct for technical limitations noted in the past) and recently
      developed subscales of the CPAQ were examined. Correlation results showed that
      the acceptance variables were reliably stronger predictors of distress and
      disability compared with coping variables. Regression analyses confirmed that,
      compared with coping variables, acceptance accounted larger unique increments in
      variance in measures of patient functioning regardless of whether the coping
      variables were given priority in the regression equations. Increasing data
      support the view that the pain management field may benefit from evolving toward
      incorporating a less control-oriented and more accommodating view of aversive
      private experiences in some circumstances.

PMID- 16291297
TI  - Further support for the pain stages of change model: suggestions for improved
      measurement.
AB  - Recent efforts to operationalize persons' readiness to adopt a self-management
      approach to chronic pain have met with promising, but somewhat limited, results.
      The current study describes the development and psychometric evaluation of a
      German version of Pain Stages of Change Questionnaire (PSOCQ). A new item pool
      was developed to attempt to improve in particular the discriminant validity of
      the scales and in order to obtain a shortened measure. The items were
      administered to 494 chronic pain patients who were split into two independent
      samples. Item- and factor-analysis performed on data from one half of the sample
      resulted in four scales: precontemplation, preparation, action, and maintenance.
      The scales of the new measure, called the "Freiburg Questionnaire-Stages of
      Chronic Pain Management (FQ-STAPM)", showed good indices of reliability,
      homogeneity, and discriminant validity. Both the concurrent and divergent
      validity indices and the relationships between scale scores and pain related
      variables proved to be consistent with the transtheoretical model. Confirmatory
      factor analysis using LISREL performed on the second half of the sample supported
      the goodness-of-fit of the structure model. Implications of these findings for
      future research exploring the relevance of the pain stages of change model are
      discussed.

PMID- 16291296
TI  - Upper limb activity over time in complex regional pain syndrome type 1 as
      objectively measured with an upper limb-activity monitor: an explorative multiple
      case study.
AB  - BACKGROUND: An upper limb-activity monitor (ULAM) has been developed to determine
      activity limitations in complex regional pain syndrome type 1 (CRPS1). The ULAM
      is based on 24h ambulatory monitoring of body segment accelerations and enables
      valid and objective quantification of mobility and upper limb activity in
      transversal studies. AIMS: To explore upper limb activity over time in acute
      upper limb CRPS1 as measured with the ULAM in a longitudinal study, and to
      compare this to time courses of other outcome measures for activity limitations
      and impairments. METHODS: Four subjects were measured four times during a
      treatment protocol. Several ULAM outcome measures related to upper limb usage and
      mobility, three questionnaires (RASQ, DASH, RAND36), and six impairment outcome
      indicators (VAS-momentary pain, VAS-pain resulting from effort, volume,
      temperature, active range of motion, strength) were used. RESULTS: Objectively
      measured upper limb activity frequently improved; improvements of >5% were found
      for 63% of the ULAM outcome measures at final assessment. The ULAM outcome
      measures had a time course more similar to the body-part and CRPS1 specific
      questionnaire RASQ than the other questionnaires. The time course of impaired
      temperature was most often in accordance with the ULAM, and both VAS scores
      showed least accordance. CONCLUSIONS: Clear changes in upper limb activity over
      time were frequently found as objectively measured with the ULAM, and
      relationships among the time courses of the ULAM and other outcome measures were
      largely explainable. The ULAM can validly assess upper limb activity over time in
      CRPS1, but between-measurement variability needs careful consideration.

PMID- 16291298
TI  - Evaluation of noncardiac chest pain: diagnostic approach, coping strategies and
      quality of life.
AB  - BACKGROUND: Approximately 30% of coronary angiograms are negative for significant
      coronary artery disease and patients are classified as having noncardiac chest
      pain (NCCP). So far, no systematic diagnostic approach to patients with NCCP
      investigating for possible esophageal, psychiatric and musculoskeletal
      abnormalities exists. Furthermore, coping strategies and quality of life are
      poorly characterized in NCCP patients. METHODS AND RESULTS: A simple diagnostic
      approach was applied to 37 consecutive patients (21 female, age 61+/-12 years)
      with angina-like chest pain and normal coronary angiograms. Twenty-one patients
      were found to suffer from psychiatric disorders (combined anxiety (A) and
      depression (D): n = 10, D: n = 5, panic disorder (P): n = 3, somatization (S): n
      = 3) based on their Symptom Check List 90 scores and according to DSM IV-R
      criteria. Sixteen patients had an improvement of their chest pain after oral
      esomeprazole (40 mg for 7 days) and were therefore diagnosed with
      gastroesophageal reflux disease (GERD). Musculoskeletal abnormalities including
      chostochondritis (n = 4), thoracic spondylodynia (n = 1), and fibromyalgia (n =
      1) were found in six patients. Multiple diagnoses were confirmed in six patients
      with GERD (additional D n = 3, additional musculoskeletal disorders n = 3).
      Patients with psychiatric disorders showed a diminished quality of life (MOS-SF
      36), more frequent chest pain, less treatment satisfaction (Seattle Angina
      Questionnaire) and more rumination (Trier Coping Scales) compared to GERD
      patients. CONCLUSIONS: Immediate combined psychiatric and orthopedic evaluation
      as well as esomeprazole administration following exclusion of coronary artery
      disease may confirm the causes of noncardiac chest pain. Identification of
      psychiatric disorders seems especially warranted since these patients experience
      a reduced quality of life and exhibit pathologic coping strategies.

PMID- 16291299
TI  - Fear of pain associated with medical procedures and illnesses.
AB  - The study was aimed at determining the dimensions of fear of pain associated with
      medical procedures and the dimensions of fear of pain associated with illnesses
      and accidents on a sample composed of young, middle-aged and elderly persons. The
      participants were 573 adults (aged 26-94 years). They were presented with (a) the
      French adaptation of the ten medical fear items from the original FPQ plus 19
      additional items, (b) the French adaptation of the 6 illness items from the
      original FPQ plus 49 additional items, and (c) an Exposure to Painful Situations
      Questionnaire. As regards the fear of medical procedures, a four-factor structure
      was identified: Examination and Care, Shots, Dental care, and Invasive
      procedures. Older participants, and less educated participants tended to show
      more fear of invasive procedures than younger participants, and more educated
      participants. As regards the fear of pain associated with illnesses, an eight
      factor solution was found: Minor ailments, cramps, infections and abscesses,
      inflamed joints, colics, breaks, lesion of organs, and cancer and terminal
      illness. Older participants tended to show more fear of pain associated with
      minor ailments, inflamed joints, breaks, colic, and cramps than younger
      participants did. Previous exposure to pain resulted in a clear decrease in fear
      of pain associated with most of medical procedures, especially invasive
      procedures and shots.

PMID- 16291300
TI  - Persistent back pain--why do physical therapy clinicians continue treatment? A
      mixed methods study of chiropractors, osteopaths and physiotherapists.
AB  - AIMS: (a) To investigate how widespread is the use of long term treatment without
      improvement amongst clinicians treating individuals with low back pain. (b) To
      study the beliefs behind the reasons why chiropractors, osteopaths and
      physiotherapists continue to treat people whose low back pain appears not to be
      improving. METHODS: A mixed methods study, including a questionnaire survey and
      qualitative analysis of semi-structured interviews. Questionnaire survey; 354/600
      (59%) clinicians equally distributed between chiropractic, osteopathy and
      physiotherapy professions. Interview study; a purposive sample of fourteen
      clinicians from each profession identified from the survey responses.
      Methodological techniques ranged from grounded theory analysis to sorting of
      categories by both the research team and the subjects themselves. RESULTS: At
      least 10% of each of the professions reported that they continued to treat
      patients with low back pain who showed almost no improvement for over three
      months. There is some indication that this is an underestimate. reasons for
      continuing unsuccessful management of low back pain were not found to be
      primarily monetary in nature; rather it appears to have much more to do with the
      scope of care that extends beyond issues addressed in the current physical
      therapy guidelines. The interview data showed that clinicians viewed their role
      as including health education and counselling rather than a 'cure or refer'
      approach. Additionally, participants raised concerns that discharging patients
      from their care meant sending them to into a therapeutic void. CONCLUSION: Long
      term treatment of patients with low back pain without objective signs of
      improvement is an established practice in a minority of clinicians studied. This
      approach contrasts with clinical guidelines that encourage self-management,
      reassurance, re-activation, and involvement of multidisciplinary teams for
      patients who do not recover. Some of the rationale provided makes a strong case
      for ongoing contact. However, the practice is also maintained through poor
      communication with other professions and mistrust of the healthcare system.

PMID- 16291301
TI  - Quantitative sensory testing: a comprehensive protocol for clinical trials.
AB  - We have compiled a comprehensive QST protocol as part of the German Research
      Network on Neuropathic Pain (DFNS) using well established tests for nearly all
      aspects of somatosensation. This protocol encompasses thermal as well as
      mechanical testing procedures. Our rationale was to test for patterns of sensory
      loss (small and large nerve fiber functions) or gain (hyperalgesia, allodynia,
      hyperpathia), and to assess both cutaneous and deep pain sensitivity. The
      practicality of the QST protocol was tested in 18 healthy subjects, 21-58 years,
      half of them female. All subjects were tested bilaterally over face, hand and
      foot. We determined thermal detection and pain thresholds including a test for
      the presence of paradoxical heat sensations, mechanical detection thresholds to
      von Frey filaments and a 64-Hz tuning fork, mechanical pain thresholds to
      pinprick stimuli and blunt pressure, stimulus-response-functions for pinprick and
      dynamic mechanical allodynia (pain to light touch), and pain summation (wind-up
      ratio) using repetitive pinprick stimulation. The full protocol took 27+/-2.3 min
      per test area. The majority of QST parameters were normally distributed only
      after logarithmic transformation (secondary normalization) except for the
      frequency of paradoxical heat sensations, cold and heat pain thresholds, and for
      vibration detection thresholds. Thresholds were usually lowest over face,
      followed by hand, and then foot. Only thermal pain thresholds, wind-up ratio and
      vibration detection thresholds were not significantly dependent on the body
      region. There was no significant right-to-left difference for any of the QST
      parameters; left-to-right correlation coefficients ranged between 0.78 and 0.97,
      thus explaining between 61% and 94% of the variance. This study has shown that a
      complete somatosensory profile of one affected area and one unaffected control
      area, which will be necessary to characterize patients with a variety of
      diseases, can be obtained within 1 h. Case examples of selected patients
      illustrate the value of z-transformed QST data for an easy survey of individual
      symptom profiles.

PMID- 16291302
TI  - The use of digitonin-permeabilized mammalian cells for measuring enzyme
      activities in the course of studies on lipid metabolism.

PMID- 16291304
TI  - Computed tomography angiography for the detection and characterization of intra
      cranial aneurysms: current status.
AB  - Multidetector computed tomography angiography (MD-CTA) of the intra-cranial
      vessels is now a routine examination, and is becoming fully integrated into the
      imaging and treatment algorithm of patients presenting with acute subarachnoid
      haemorrhage in many centres in the UK and Europe. The development and current
      status of CTA for cerebral aneurysms, and the strengths and limitations of this
      technique are herein reviewed.

PMID- 16291305
TI  - Use of imaging in the management of malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is an increasingly prevalent tumour. The
      death rate associated with MPM is predicted to peak in the next 10 years,
      although radiologists and clinicians will be encountering cases for the next few
      decades. Contrast-enhanced CT is an established technique for evaluating
      suspected malignant pleural disease, but MPM can be reliably diagnosed only by
      histological sampling. However, even with adequate sampling and the use of
      immunocytochemistry, histological diagnosis is known to be difficult; definitive
      diagnosis may involve a combination of clinical presentation, radiological and
      histological appearances. Percutaneous biopsy is a promising technique for
      sampling the pleura. In view of its pattern of growth, MPM is a challenging
      disease to image by any method, and it behaves quite differently from lung
      cancer. This review aims to highlight the practical aspects of assessing
      malignant pleural mesothelioma.

PMID- 16291306
TI  - Testicular varicoceles.
AB  - A testicular varicocele represents an abnormal degree of venous dilatation of the
      pampiniform plexus. It is a relatively common condition and may present at
      scrotal pain and swelling. An association with male subfertility is an area of
      debate. This article describes the present day radiological criteria and imaging
      techniques to aid accurate diagnosis of varicoceles. In addition, the role of the
      interventional radiologist in treating this condition is discussed.

PMID- 16291307
TI  - Multi-detector row computed tomography: imaging in acute aortic syndrome.
AB  - Acute aortic syndromes (AAS) encompass a spectrum of emergencies. These include
      those non-traumatic disease entities of the aorta namely, penetrating
      atherosclerotic ulcer, intramural haematoma, dissection and aneurysm rupture. The
      various types of AAS cannot be reliably differentiated on clinical grounds alone.
      Acute thoracic aortic injury is usually included in this group even though
      clinical presentation is different, i.e., in the context of trauma, the imaging
      features are very similar. Differentiation of AAS from acute coronary syndrome
      (ACS) is important, however, it must be remembered that ACS may occur as a result
      of AAS. Now electrocardiogram (ECG)-gating technology is widely available, ECG
      gated multi-detector row computed tomography (MDCT) is a powerful clinical tool
      in the acute emergency setting, which enables rapid and specific diagnosis of
      aortic pathology. ECG-gated MDCT significantly reduces motion artefact, avoids
      potential pitfalls in diagnosis and often provides diagnostic information about
      the coronary arteries. It should be used as a first-line imaging technique. This
      article examines the role of MDCT imaging and cardiac gating in the assessment of
      AAS and discusses the differentiation of this spectrum of aortic diseases with
      reference to the key imaging findings as obtained by experience in our
      institution.

PMID- 16291308
TI  - Computed tomography pseudofractures of the mid face and skull base.
AB  - Thin-section multislice CT delineates numerous normal skull-base and mid-facial
      bony discontinuities. These represent sutures, fissures and neurovascular
      foramina or channels, and should be differentiated from fractures. This pictorial
      review describes and illustrates the characteristic location and multiplanar CT
      appearances of these structures. Their clinical significance in terms of
      pathological processes and surgical planning are discussed.

PMID- 16291309
TI  - Multidetector-row CT of right hemidiaphragmatic rupture caused by blunt trauma: a
      review of 12 cases.
AB  - AIM: To determine the usefulness of multidetector-row CT (MDCT) with multiplanar
      reformatted (MPR) images in the sagittal and coronal plane in diagnosing acute
      right hemidiaphragmatic rupture. MATERIALS AND METHODS: Twelve patients were
      identified who received chest and abdominal MDCT after major blunt trauma
      diagnosed with right diaphragmatic injury. Sagittal and coronal reformations were
      performed in all cases. The images were retrospectively reviewed by two
      experienced radiologists for signs of right diaphragm injury, such as direct
      diaphragm discontinuity, the "collar sign", the "dependent viscera sign", and
      intra-thoracic location of herniated abdominal contents. RESULTS: Of the 12 cases
      of right hemidiaphragm rupture, diaphragm discontinuity was seen in seven (58%)
      cases, the collar sign in five (42%), the dependent viscera sign in four (33%),
      and transdiaphragmatic herniation of the right colon and fat in another. Two
      variants of the collar sign were apparent on high-quality sagittal and coronal
      reformations. The first, termed the "hump sign", describes a rounded portion of
      liver herniating through the diaphragm forming a hump-shaped mass, and the
      second, termed the "band sign," is a linear lucency across the liver along the
      torn edges of the hemidiaphragm. The hump sign occurred in 10 (83%) patients and
      the band sign in four (33%). CONCLUSION: MDCT is very useful in the diagnosis of
      right hemidiaphragm injury caused by blunt trauma when sagittal and coronal
      reformatted images are obtained, and should allow more frequent preoperative
      diagnosis.

PMID- 16291310
TI  - Failure of aneurysm sac shrinkage after endovascular repair; the effect of mural
      calcification.
AB  - AIM: To evaluate the effect of abdominal aortic aneurysm wall calcification on
      subsequent sac shrinkage after endovascular repair. MATERIALS AND METHODS:
      Seventy-three patients underwent endovascular aneurysm repair. The degree of sac
      wall calcification on pre-procedural computed tomography (CT) examination was
      graded from 1 to 4 according to the degree of circumferential involvement. On
      follow-up CT imaging, the maximum transverse diameter (MTD) of the sac was
      recorded, as well as the presence or absence of endoleak. In those patients with
      a non-shrinking aneurysm, but no CT evidence of endoleak, contrast-enhanced
      ultrasound (USS) was performed. Any patient with an endoleak, however diagnosed,
      was excluded from the study. Kruskal-Wallis and Spearman's rank correlation
      coefficient testing was applied to compare the degree of calcification and change
      in MTD. RESULTS: Sixty-three pre-procedural CT images were available for
      calcification grading. Six of this group had endoleaks resulting in 57 sets of
      data being available for the study. A reduction in MTD occurred in 68.25% of
      these patients by 1 year post-procedure. Our figures show aortic calcification is
      inversely associated with MTD reduction at 6 months (p = 0.01), 1 year (p = 0.05)
      and 2 years (p = 0.05). CONCLUSION: This study indicates that the degree of
      aortic wall calcification is significant in predicting MTD reduction post
      endovascular repair. The possible mechanisms and implications of this are
      discussed.

PMID- 16291311
TI  - The relationship between limited MRI section analyses and volumetric assessment
      of synovitis in knee osteoarthritis.
AB  - AIM: To assess whether simple, limited section analysis can replace detailed
      volumetric assessment of synovitis in patients with osteoarthritis (OA) of the
      knee using contrast-enhanced magnetic resonance imaging (MRI). MATERIALS AND
      METHODS: Thirty-five patients with clinical and radiographic OA of the knee were
      assessed for synovitis using gadolinium-enhanced MRI. The volume of enhancing
      synovium was quantitatively assessed in four anatomical sites (the medial and
      lateral parapatellar recesses, the intercondylar notch and the suprapatellar
      pouch) by summing the volumes of synovitis in consecutive sections. Four
      different combinations of section analysis were evaluated for their ability to
      predict total synovial volume. RESULTS: A total of 114 intra-articular sites were
      assessed. Simple linear regression demonstrated that the best predictor of total
      synovial volume was the analysis containing the inferior, mid and superior
      sections of each of the intra-articular sites, which predicted between 40-80%
      (r(2) = 0.396, p < 0.001 for notch; r(2) = 0.818, p < 0.001 for medial
      parapatellar recess) of the total volume assessment. CONCLUSIONS: The results
      suggest that a three-section analysis on axial post-gadolinium sequences provides
      a simple surrogate measure of synovial volume in OA knees.

PMID- 16291312
TI  - Imaging meningiomas: is there a need for post-contrast FLAIR?
AB  - AIM: The aim of this study was to compare post-contrast fluid-attenuated
      inversion recovery (FLAIR) imaging with post-contrast T1-weighted images (T1WI)
      in depicting meningiomas. MATERIALS AND METHODS: Twenty-nine patients with 46
      meningiomas were included in this study. FLAIR and T1WI were obtained before and
      after intravenous administration of gadopentetate dimeglumine. The contrast
      enhancement degree, contrast enhancement pattern, lesion conspicuity, and the
      detection of the dural sign were compared between post-contrast FLAIR images and
      post-contrast T1WI. RESULTS: The enhencement degree on FLAIR was equal or less
      than T1WI for all meningiomas. Among 46 meningiomas 38 (83%) enhanced
      homogeneously and eight (17%) inhomogeneously on T1WI. On contrast-enhanced FLAIR
      images, of the total 46 meningiomas 22 (48%) enhanced homogeneously, eight (17%)
      inhomogeneously, whereas 14 (30%) meningiomas showed a peripheral rim enhancement
      not observed on T1WI. Two (5%) meningiomas showed no contrast enhancement on post
      contrast FLAIR images. Among the 14 meningiomas showing rim enhancement using
      FLAIR imaging, 12 (85%) were measured to be 2 cm or more in diameter. A dural
      tail sign was found in 16 (35%) and 23 (50%) meningiomas on post-contrast T1WI
      and FLAIR images, respectively. CONCLUSION: In contrast to other extra-axial
      diseases, post-contrast FLAIR sequence was not found to be a valuable adjunct to
      contrast-enhanced T1WI in the depiction of meningiomas.

PMID- 16291313
TI  - A case of multiple chondrosarcomas secondary to severe multiple symmetrical
      enchondromatosis (Ollier's disease) at an early age.

PMID- 16291314
TI  - NICE guidelines for the management of acute head injury.

PMID- 16291315
TI  - Re: accuracy rates of reporting of intravenous urograms: a comparison of
      radiographers with radiology specialist registrars.

PMID- 16291316
TI  - Radiological digital teaching file development: an overview.

PMID- 16291318
TI  - The removal of forearm plates in children.
AB  - Routine removal of forearm plates in children remains controversial. The aim of
      the study was to assess if risks of complications associated with removal of
      forearm plates in children warrant routine removal of these plates. A total of 43
      children (mean age 10.6 years old at time of fracture fixation) who had forearm
      plates removed after fracture fixation in our unit over a 10-year period were
      reviewed. There were three cases of re-fractures (two in the same child), all of
      which occurred following an episode of trauma and the use of Dynamic Compression
      Plates (DCP). One case of superficial infection was successfully treated with
      oral antibiotics. Low rates of complications from routine removal of metal work
      after forearm plating in children may be achieved.

PMID- 16291320
TI  - Advances in articular cartilage repair.
AB  - Many joint and systemic disorders may lead to cartilage defects. Partial
      thickness defects of the articular cartilage do not have healing potential. When
      the lesion reaches the subchondral bone, spontaneous healing may be observed, but
      consists of fibrocartilaginous tissue. The main efforts for cartilage repair are
      targeted at filling of the cartilage defect with a tissue that possesses the same
      mechanical properties with hyaline cartilage and the consolidation of this tissue
      with the native articular cartilage. There are various arthroscopic techniques
      and although they provide pain relief, they do not restore the damaged cartilage.
      Osteochondral transplantation is more effective in dealing with small or medium
      size full thickness defects, but further efforts are required in order to reduce
      the donor site morbidity, marginal necrosis and partial covering of the defect.

PMID- 16291321
TI  - Classification of non-union.
AB  - A substantial number of experimental and clinical studies have established that
      the cornerstones for successful bone-healing are biomechanical stability and
      biological vitality of the bone, as they both provide an environment in which new
      bone can be formed. Non-union of long bones is a significant consequence in
      treating fractures. Many approaches to prevent fracture non-union have been
      proposed. Depending on the type and location of the non-union, treatment options
      include various types of bone fixation, with or without supplemental bone graft
      or other biophysical enhancements.

PMID- 16291322
TI  - Bone scaffolds: the role of mechanical stability and instrumentation.
AB  - Osteoconductive bone scaffolds are increasingly used today for regeneration of
      bone defects. Research is mainly focused on the scaffold material, its macro and
      micro architecture and mechanical properties. The mechanical environment and the
      optimal instrumentation, used to protect and enhance bone regeneration, are
      multifactorial issues and have not yet received the appropriate attention by
      researchers in the field.

PMID- 16291323
TI  - Mechanical and biological treatment of long bone non-unions.
AB  - Non-union (NU) of bones is a multifactorial phenomenon. Infected non-unions
      and/or those with bone loss require "biological treatment", such as the excision
      of the pathological infected non-union site or the "creation" of new bone
      substance by the use of distraction techniques. The treatment of choice that
      meets both the biological and mechanical requirements is that of the external
      fixation, in as much as it has an extremely low septic complication rate and the
      mechanical environment can be varied automatically or programmed depending on the
      requirements. The authors report on a total of 287 cases of non-union treated
      with external fixation, with a 93% success rate.

PMID- 16291324
TI  - Application of recombinant BMP-7 on persistent upper and lower limb non-unions.
AB  - The purpose of this study was to evaluate the efficacy and safety of recombinant
      bone morphogenetic protein 7 (rhBMP-7 or OP-1) as a bone-stimulating agent in the
      treatment of persistent fracture non-unions. Twenty-five consecutive patients [19
      males, mean age 39.4 years (range: 18-79)] with 26 fracture non-unions were
      treated with rhBMP-7. There were 10 tibial non-unions, eight femoral, three
      humeral, three ulnar, one patellar, and one clavicular non-union. The mean follow
      up was 15.3 months. The mean number of operations performed prior to rhBMP-7
      application was 3.2, with autologous bone graft and bone marrow injection being
      used in 10 cases (38.5%). Both clinical and radiological union occurred in 24
      (92.3%) cases, within a mean time of 4.2 months and 5.6 months, respectively. Of
      the remaining two cases, one patient ultimately underwent a below knee
      amputation, secondary to recurrence of deep sepsis. The other patient with
      recalcitrant ulnar non-union although the radiological union was incomplete,
      declined further intervention, as he was asymptomatic. No complications or
      adverse effects from the use of rhBMP-7 were encountered. This study supports the
      view that the application of rhBMP-7 as a bone-stimulating agent is safe and a
      power adjunct to be considered in the surgeon's armamentarium for the treatment
      of these challenging clinical conditions.

PMID- 16291325
TI  - Applications of nanotechnologies in medical practice.
AB  - As medical practice enters a new era with the exciting new applications of
      nanoscience and technology, the paper introduces the philosophy and the
      principles of controlled drug delivery and the generation of tissue. It further
      describes and discusses new research into nanoporous materials and how
      encapsulation of various medical substances can create stimuli-controlled
      precision delivery systems. The paper goes on to highlight the process of those
      new materials for medical applications citing particularly a successful process
      for coating them onto flexible materials such as fabrics.

PMID- 16291338
TI  - Making the National Children's Study a real partnership with academic pediatrics.

PMID- 16291339
TI  - In defense of a single standard of research risk for all children.

PMID- 16291340
TI  - Prenatal counseling and resuscitation decisions at extremely premature gestation.

PMID- 16291341
TI  - Improving patient outcomes by standardizing care.

PMID- 16291342
TI  - Improving behavior of lead-exposed children: micronutrient supplementation,
      chelation, or prevention.

PMID- 16291343
TI  - Sorting out the causes of ALPS.

PMID- 16291344
TI  - What is a "minor" increase over minimal risk?

PMID- 16291345
TI  - The ethics of neonatal resuscitation at the margins of viability: informed
      consent and outcomes.
AB  - OBJECTIVES: To determine the adequacy of records of parental counseling in
      mothers with threatened preterm delivery before 27 weeks gestation, whether
      interventions performed at birth were consistent with recorded antenatal
      decisions and whether extent of resuscitation affected the occurrence of serious
      short-term morbidity. STUDY DESIGN: Antenatal consultation records and records of
      resuscitation and short-term outcomes were analyzed of 65 mothers with threatened
      delivery at 21 weeks to 26 weeks and 6 days gestation, and their 61 infants who
      delivered before 27 weeks. RESULTS: Discussions about survival rates and the
      frequency of handicap were more likely to be recorded before 25 weeks gestation
      than after; the adequacy of the records varied among individuals. A decision not
      to resuscitate was present in 6 of the 13 consultations performed before 23 weeks
      gestation, and in none of the 52 at 23 weeks or above. A decision to resuscitate
      only if the infant's condition at birth was good was found in 7 consultations, 6
      of which were at less than 24 weeks gestation. All infants born at 23 weeks and
      above were resuscitated, including the infants with conditional resuscitation
      decisions. Three of the 6 infants receiving heart massage were discharged alive
      without major short-term morbidity (severe intracranial hemorrhage,
      periventricular leukomalacia, or threshold retinopathy). All 8 infants of less
      than 25 weeks gestation with a heart rate at 3 minutes that was still less than
      100 beats/min, in spite of active resuscitation, either died or had major short
      term morbidity. CONCLUSIONS: Records of antenatal consultations were often
      lacking important information. Variations in physician documentation practices
      are substantial and affect the care offered to infants at the threshold of
      viability. Even extensive resuscitation can be followed by intact survival if the
      resuscitation required is brief.

PMID- 16291346
TI  - Serum testosterone and estradiol in sudden infant death.
AB  - OBJECTIVE: To test the hypothesis that among infants who die unexpectedly,
      testosterone and/or estradiol levels are elevated in those diagnosed with SIDS
      versus those with known causes of death (controls). STUDY DESIGN: Postmortem
      blood was collected and coded from infant autopsies, and serum was prepared and
      frozen until assayed for total testosterone and estradiol by fluoroimmunoassay.
      Subject information was then collected from the medical examiner's report.
      RESULTS: Testosterone, but not estradiol, was significantly higher in 127 SIDS
      cases versus 42 controls for both males (4.8 +/- 0.4 vs 2.2 +/- 0.4 nmol,
      respectively; P < .005) and females (2.4 +/- 0.2 vs 1.6 +/- 0.2 nmol,
      respectively; P < 0.03). CONCLUSIONS: Higher testosterone levels in infant
      victims of unexpected, unexplained death may indicate a role for testosterone or
      related steroids in SIDS. Further research is needed to understand the potential
      utility of testosterone as an indicator of SIDS risk.

PMID- 16291347
TI  - Prenatal impairment of brain serotonergic transmission in infants.
AB  - OBJECTIVE: To evaluate whether the free fraction of L-tryptophan (L-Trp) and the
      N1/P2 component of the auditory evoked potentials (AEPs) are associated with
      impaired brain serotonin neurotransmission in infants with intrauterine growth
      restriction (IUGR). STUDY DESIGN: We measured free, bound, and total plasma L-Trp
      and recorded the N1/P2 component of AEP in a prospective, longitudinal, and
      comparative study comparing IUGR and control infants. RESULTS: Plasma free L-Trp
      was increased and the amplitude of N1/P2 component was significantly decreased in
      IUGR relative to control infants. The free fraction of L-Trp and N1/P2 component
      had a negative association. CONCLUSIONS: In newborns with IUGR, the changes in
      measured plasma free fraction of L-Trp and in the amplitude the N1/P2 component
      of the AEP suggest an inverse association between free L-Trp and components of
      the AEP. The changes observed in the free fraction of L-Trp and AEP may be
      causally associated with brain serotonergic activity in utero. In IUGR,
      epigenetic factors such as stress-induced disturbances in brain serotonin
      metabolism or serotonergic activity, identifiable by alterations in AEP,
      influence cerebral sensory cortex development and may be causally associated with
      serotonin-related disorders in adulthood.

PMID- 16291348
TI  - Neonatal outcome in twin-to-twin transfusion syndrome treated with fetoscopic
      laser occlusion of vascular anastomoses.
AB  - OBJECTIVE: To determine neonatal mortality and morbidity rates in monochorionic
      twins with chronic twin-to-twin transfusion syndrome (TTTS) treated with
      fetoscopic laser occlusion of vascular anastomoses. STUDY DESIGN: In a
      prospective study of monochorionic twins delivered at our center between June
      2002 and December 2004, neonatal outcome was assessed in 40 monochorionic twin
      pairs with TTTS treated with laser compared with 46 monochorionic twin pairs
      without TTTS. RESULTS: The neonatal mortality rate in the TTTS and no-TTTS group
      was 8% (6/76) and 3% (3/90), respectively. The rate of severe cerebral lesions on
      ultrasound scanning in the TTTS and no-TTTS group was 14% (10/72) and 6% (5/82),
      respectively. The incidence of adverse neonatal outcome (neonatal death, major
      neonatal morbidity, or severe cerebral lesions) in the TTTS and no-TTTS group
      was, respectively, 26% (20/76) and 13% (12/90) (RR = 1.97, 95% CI = 1.03 to
      3.77). CONCLUSIONS: Although perinatal outcome in TTTS has improved after laser
      therapy, neonatal mortality and morbidity rates remain high. Relative risk for
      adverse neonatal outcome is increased 2-fold in TTTS treated with laser relative
      to monochorionic twins without TTTS.

PMID- 16291349
TI  - Potential costs and benefits of newborn screening for severe combined
      immunodeficiency.
AB  - OBJECTIVE: Severe combined immunodeficiency (SCID) is a rare, treatable disorder
      of the immune system. The incidence is unknown but may be more common than
      published estimates because infants frequently die of infection before diagnosis.
      SCID is a candidate for universal newborn screening, so there is a need to
      determine under which circumstances screening would be cost-effective. STUDY
      DESIGN: We assumed a screening program for SCID would use T-cell lymphopenia as
      the screening criterion and performed a cost-utility analysis comparing universal
      screening with screening only those with a family history of SCID. RESULTS:
      Assuming society is willing to pay $50,000 for every quality-adjusted life-year
      saved, a SCID screening test that cost less than $5 with a false-negative rate of
      0.9% and a false-positive rate of 0.4% would be considered cost-effective. A
      nationwide screening program would cost an additional $23.9 million per year for
      screening costs but would result in 760 years of life saved per year of
      screening. The cost to detect 1 case of SCID would be $485,000. CONCLUSION: SCID
      screening could result in a large benefit to detected individuals, making
      screening relatively cost-effective in spite of the low incidence of the disease.
      However, an adequate test is critical to cost-effectiveness.

PMID- 16291350
TI  - Early brain injury in premature newborns detected with magnetic resonance imaging
      is associated with adverse early neurodevelopmental outcome.
AB  - OBJECTIVE: To determine the neurodevelopmental outcome of prematurely born
      newborns with magnetic resonance imaging (MRI) abnormalities. STUDY DESIGN: A
      total of 89 prematurely born newborns (median age 28 weeks postgestation) were
      studied with MRI when stable for transport to MRI (median age, 32 weeks
      postgestation); 50 newborns were studied again near term age (median age, 37
      weeks). Neurodevelopmental outcome was determined at 18 months adjusted age
      (median) using the Mental Development Index (Bayley Scales Infant Development II)
      and a standardized neurologic exam. RESULTS: Of 86 neonatal survivors, outcome
      was normal in 51 (59%), borderline in 22 (26%), and abnormal in 13 (15%).
      Moderate/severe MRI abnormalities were common on the first (37%) and second (32%)
      scans. Abnormal outcome was associated with increasing severity of white matter
      injury, ventriculomegaly, and intraventricular hemorrhage on MRI, as well as
      moderate/severe abnormalities on the first (relative risk [RR] = 5.6; P = .002)
      and second MRI studies (RR = 5.3; P = .03). Neuromotor abnormalities on
      neurologic examination near term age (RR = 6.5; P = .04) and postnatal infection
      (RR = 4.0; P = .01) also increased the risk for abnormal neurodevelopmental
      outcome. CONCLUSIONS: In premature newborns, brain abnormalities are common on
      MRI early in life and are associated with adverse neurodevelopmental outcome.

PMID- 16291351
TI  - Does bronchodilator responsiveness in infants with bronchiolitis depend on age?
AB  - OBJECTIVE: To assess the relation between age and bronchodilator responsiveness
      in infants with bronchiolitis. STUDY DESIGN: In 41 infants (age, 2 to 18 months)
      with bronchiolitis, lung function was measured with the raised volume rapid
      thoracoabdominal compression technique before and after salbutamol inhalation.
      Lung function was quantified in terms of timed volumes (FEV(0.5), FEV(0.75), and
      FEV(1.0)). A significant change was defined as a postbronchodilator value that
      differed from baseline by more than twice the within-subject coefficient of
      variation. RESULTS: For the group, postbronchodilator values did not differ
      significantly from baseline (DeltaFEV(0.5), 3.8% +/- 9.3%; DeltaFEV(0.75), 3.5%
      +/- 9.5%; and DeltaFEV(1.0), 4.0 +/- 9.8%). Eleven subjects showed significantly
      increased timed volumes; 3 presented with a decreased lung function; the
      remaining patients failed to show a significant change. The mean age of subjects
      with improved lung function did not differ significantly from the mean age of
      those with no or paradoxical responses (9.7 +/- 4.7 vs 8.1 +/- 4.1 months); there
      was no correlation of age with the size of the bronchodilator response.
      CONCLUSIONS: The results of the current study indicate that bronchodilator
      responsiveness in infants with bronchiolitis is not age-dependent.

PMID- 16291352
TI  - A clinical pathway for bronchiolitis is effective in reducing readmission rates.
AB  - OBJECTIVE: To examine the use of a clinical pathway in the management of infants
      hospitalized with acute viral bronchiolitis. STUDY DESIGN: A clinical pathway
      with specific management and discharge criteria for the care of infants with
      bronchiolitis was developed from pathways used in tertiary care pediatric
      institutions in Australia. Two hundred and twenty-nine infants admitted to
      hospital with acute viral bronchiolitis and prospectively managed using a pathway
      protocol were compared with a retrospective analysis of 207 infants managed
      without a pathway in 3 regional and 1 tertiary care hospital. RESULTS:
      Readmission to hospital was significantly lower in the pathway group (P = .001),
      as was administration of supplemental fluids (P = .001) and use of steroids (P =
      .005). There were no differences between groups in demographic factors or
      clinical severity. The pathway had no overall effect on length of stay or time in
      oxygen. CONCLUSIONS: A clinical pathway specifying local practice guidelines and
      discharge criteria can reduce the risk of readmission to hospital, the use of
      inappropriate therapies, and help with discharge planning.

PMID- 16291353
TI  - Aerosol delivery in respiratory syncytial virus bronchiolitis: hood or face mask?
AB  - OBJECTIVES: To compare the utility of the hood versus the face mask for delivery
      of inhaled medications to infants hospitalized with viral bronchiolitis. STUDY
      DESIGN: Randomized, double-blinded, controlled trial; 49 hospitalized infants
      with viral bronchiolitis, age 2.75 +/- 2.2 months (mean +/- SD), were grouped to
      either the hood (n = 25) or the mask (n = 24). Each subject received inhalation
      treatments with the use of both devices. Half of the Hood Group received the
      active drug treatment (1.5 mg epinephrine in 4 mL saline [3%]) via hood followed
      immediately by placebo treatment (normal saline) via mask, whereas the other half
      received the opposite order. Half of the Mask Group received the active drug
      treatment via mask followed immediately by placebo treatment via hood, whereas
      the other half received the opposite order. Therapy was repeated 3 times daily
      until discharge. Outcome measures included clinical scores and parental
      preference. RESULTS: Percent improvement in clinical severity scores after
      inhalation was significant in both groups on days 1, 2, and 3 after admission
      (Hood Group: 15%, 15.4%, and 16.4%, respectively; Mask Group: 17.5%, 12.1%, and
      12.7%, respectively; P < .001). No significant difference in clinical scores
      improvement between groups was observed. Eighty percent (39/49) of parents
      favored the hood over the mask; 18% (9/49) preferred the mask and 2% (1/49) were
      indifferent. CONCLUSIONS: In infants hospitalized with viral bronchiolitis and in
      whom aerosol treatment is considered, aerosol delivery by hood is as effective as
      by mask. However, according to parents, the tolerability of the hood is
      significantly better than that of a mask.

PMID- 16291354
TI  - Iron and zinc supplementation does not improve parent or teacher ratings of
      behavior in first grade Mexican children exposed to lead.
AB  - OBJECTIVE: To determine the efficacy of iron and zinc supplementation on behavior
      ratings of lead-exposed children. STUDY DESIGN: In this double-blind, randomized
      trial, 602 first-grade children received 30 mg ferrous fumarate, 30 mg zinc
      oxide, both, or placebo daily for 6 months. Lead, iron, and zinc status were
      determined at baseline and follow-up. Parents and teachers provided ratings of
      child behavior using the Conners Rating Scales. RESULTS: The baseline mean (SD)
      blood lead concentration was 11.5 (6.1) mug/dL, with 51% of children > or = 10
      microg/dL. The prevalence of attention deficit hyperactivity disorder, estimated
      by combined parent and teacher ratings, was 6%. At follow-up, parent ratings of
      oppositional, hyperactive, cognitive problems, and attention deficit
      hyperactivity disorder decreased by 1.5, 1.2, 2.5, and 3.4 points, respectively
      (P < .05). Teacher ratings of hyperactivity increased by 1.1 points (P = .008),
      and the mean cognitive problem score declined by 0.7 points (P = .038). There
      were no treatment effects on mean change in scores, but children receiving any
      zinc had a higher likelihood of no longer receiving clinically-significant
      teacher ratings of oppositional behaviors. CONCLUSIONS: This regimen of
      supplementation did not result in consistent improvements in ratings of behavior
      in lead-exposed children over 6 months.

PMID- 16291355
TI  - Renal glycosuria: occurrence in two siblings and a review of the literature.

PMID- 16291356
TI  - Transient bulging fontanelle after vaccination: case report and review of the
      vaccine adverse event reporting system.
AB  - OBJECTIVE: To describe the features of transient bulging fontanelle (TBF) after
      vaccination. STUDY DESIGN: We searched the Vaccine Adverse Event Reporting System
      database for reports describing bulging fontanelle. We defined a definite TBF
      case as a patient with a bulging fontanelle, normal neuroimaging and
      cerebrospinal fluid analysis, and absence of a depressed level of consciousness,
      focal neurologic findings, or identified cause. Follow-up had to reveal normal
      development. Probable cases lacked either lumbar puncture or neuroimaging or both
      but met all other criteria. RESULTS: We identified 18 patients with definite or
      probable TBF. The median age at presentation was 4.5 months, interval from
      vaccination to symptom onset was 18 hours, and time to resolution was 3 days.
      Fifteen children were febrile. CONCLUSIONS: We cannot conclude that vaccines
      cause TBF. Further controlled studies are necessary. Even if further research
      verifies TBF as a rare side effect, immunization benefits would still vastly
      outweigh this hypothetical risk. However, confirmation of a vaccine association
      could modify the management of infants who develop TBF after immunizations.

PMID- 16291357
TI  - Clinical impact of corticosteroid-induced adrenal suppression during treatment
      for acute lymphoblastic leukemia in children: a prospective observational study
      using the low-dose adrenocorticotropin test.
AB  - OBJECTIVES: To investigate how frequently adrenal function fails to recover after
      corticosteroid therapy in children with acute lymphoblastic leukemia and to
      explore the clinical impact of slow adrenal recovery without steroid
      substitution. STUDY DESIGN: Low-dose (1 microg) adrenocorticotropic hormone tests
      were performed before and after steroid courses and during infectious episodes in
      24 children. Test results were not available during the study. RESULTS: All 13
      patients tested before treatment had normal adrenal responses. Adrenal
      suppression was found in 8 (47%) of 17 patients 5 days after discontinuation of a
      5-week induction course of prednisolone and in 1 (20%) of 5 patients 7 days after
      a 3-week intensification course of dexamethasone, both courses being tapered over
      9 days, as well as in all 13 patients tested 2 days after a 1-week prednisolone
      course. Clinically significant manifestations of adrenal suppression were noted
      in 3 (12%) patients. Of 204 scheduled tests, 131 were performed. CONCLUSIONS:
      High-dose glucocorticoid therapy may cause adrenal suppression lasting more than
      1 week in children with acute lymphoblastic leukemia, even after tapering the
      dose. We suggest steroid replacement during stress episodes within 1 to 2 weeks
      after discontinuation and thereafter testing adrenal function selectively in
      accordance with symptoms.

PMID- 16291358
TI  - Adolescent obesity is associated with high ambulatory blood pressure and
      increased carotid intimal-medial thickness.
AB  - OBJECTIVES: To investigate 24-hour ambulatory blood pressure, lipid profiles, and
      carotid artery intimal-medial thickness (IMT) in adolescents with and without
      obesity. STUDY DESIGN: Ambulatory blood pressure data from 93 consecutive
      adolescents referred to our hypertension center for possible hypertension were
      analyzed. Fasting serum glucose and lipid concentrations were measured in all
      subjects. Carotid artery IMT was also measured by B-mode ultrasound imaging in
      all patients. Obesity was defined as body mass index > or =95(th) percentile for
      age and sex. Twenty-two of the subjects were obese and 71 nonobese. RESULTS: Mean
      24-hour, daytime, and nighttime systolic blood pressures were significantly
      higher in obese subjects compared with nonobese subjects (P < .002). Twenty-four
      hour, daytime, and nighttime pulse pressures were also significantly higher in
      obese subjects (P < .001). The magnitude of systolic white coat effect was
      significantly higher in obese subjects (P < .006) and white coat hypertension was
      significantly more frequent in obese subjects (P < .0001). Obese subjects had
      higher triglycerides (P < .001) and lower HDL cholesterol (P < .01) than nonobese
      subjects. Finally, obese adolescents had thicker mean IMT of internal carotid
      arteries than nonobese adolescents (P < .005). CONCLUSIONS: Obese adolescents
      have higher ambulatory blood pressure and higher carotid artery IMT, possibly
      indicating an early course of obesity-related hypertension and carotid artery
      structural alterations.

PMID- 16291359
TI  - Clopidogrel use in children.
AB  - OBJECTIVES: To review a pediatric experience with the antiplatelet agent
      clopidogrel and suggest a dosage regimen. STUDY DESIGN: A retrospective chart
      review of all infants and children treated with clopidogrel at The Hospital for
      Sick Children, Toronto between January 2001 and April 2004. Clopidogrel dosages,
      duration of therapy, complications, and adverse effects in a pediatric population
      were explored. RESULTS: Fifteen infants and children with congenital and acquired
      heart disease were treated with clopidogrel (median age, 3.5 years; range, 6
      weeks to 16 years). Dosages ranged from 1 to 6 mg/kg/day for periods between 1
      month and 6 months. Although no thrombotic events were reported, 1 child had a
      bleeding complication (gastrointestinal) while on triple antithrombotic therapy.
      Other complications reported in adults, including rash and clinical
      thrombocytopenia, were not noted in this pediatric series. CONCLUSIONS:
      Clopidogrel was well tolerated. We suggest a starting dose of 1 mg/kg/day for
      children.

PMID- 16291360
TI  - Catch-up growth of supine length/height of very low birth weight, small for
      gestational age preterm infants to adulthood.
AB  - OBJECTIVE: To analyze linear growth of very low birth weight (VLBW), small for
      gestational age (SGA; < 10th percentile) preterm infants from birth as to catch
      up or no catch-up growth. STUDY DESIGN: VLBW SGA preterm infants (n = 46) with
      primarily symmetric intrauterine growth restriction from the Bonn Longitudinal
      Study were compared with 62 appropriate for gestational age (AGA) VLBW preterm
      and 73 term infants and with their parents. RESULTS: Forty-six percent of VLBW
      SGA (21 of 46) had complete height catch-up by adult age, and most became taller
      than target height (TH) (15 of 21; 71%). The others did not catch up; most of
      them remained shorter than TH (18 of 25; 72%) after initial catch-up followed by
      catch-down growth. Mean adult height z-score was lower than that for birth
      length. Mean body mass index was similar in the catch-up and no catch-up groups
      (21.8 and 21.3, respectively) and lower than in the controls (23.2).
      Approximately 1/2 of the head circumference (HC) catch-up children achieved
      height catch-up as well. CONCLUSIONS: Height catch-up extended beyond age 6
      years, independent of HC growth. We could not predict height catch-down or
      successful catch-up.

PMID- 16291361
TI  - Diamond-blackfan anemia and growth status: the French registry.
AB  - OBJECTIVES: To study the frequency and risk factors of growth retardation (GR) in
      patients with Diamond-Blackfan anemia. STUDY DESIGN: A cross-sectional survey
      including the 95 patients followed by hematologists affiliated with the French
      Society of Pediatric Hematology and Immunology for whom growth data were
      available; 43 patients were transfusion dependent, 32 were steroid dependent, and
      20 patients were off treatment. GR was defined as height below 2 SD. RESULTS:
      Growth retardation was observed in 29.5% (28) patients. The proportion of GR
      increased significantly with age (16% <10, 32% among 10 to 16, 47.6% among 17 to
      25, 41.7% among >16 years) and was higher in on-treatment than in off-treatment
      patients (35% among transfusion-dependent, 37% among steroid-dependent vs 5%
      among off-treatment). GR was significantly linked to associated malformations
      (OR, 2.3 [1.1 to 8.0]; P = .02) and intrauterine growth retardation (OR, 6.0 [1.1
      to 11.6]; P = .021). GR remained independently associated with age,
      malformations, and treatment in a logistic regression. CONCLUSIONS: Our study
      showed that the risk of GR increases with age and is associated with treatment
      dependence. This result addresses the question of the respective part, in the
      pathogenesis of GR, of the disease severity, illustrated by treatment dependence
      on the one hand and of the deleterious effects of long-term treatments on the
      other hand.

PMID- 16291362
TI  - Growth-reductive therapy in children with marfan syndrome.
AB  - OBJECTIVES: To determine the accuracy and precision of 2 height-prediction
      methods in Marfan syndrome and to assess the growth-reductive effect and side
      effects of sex hormone treatment. STUDY DESIGN: In a retrospective study in 31
      untreated (17 boys) and 43 treated patients (21 boys) with Marfan syndrome, we
      assessed bone age and predicted adult height by 2 methods. The accuracy of the
      methods was assessed in the untreated group. The effect of therapy was corrected
      for outcome in the untreated group and other confounding variables with
      multivariate analysis. RESULTS: Accuracy strongly varied with sex, chronological
      age, and prediction method. Overall precision was low. Treatment was started at a
      mean age of 12.8 +/- 1.4 years (boys) and 11.4 +/- 1.2 years (girls). With
      multiple regression analysis, a statistically significant effect was observed
      only in boys using a pharmacologic dosage (5.5 cm, 95% CI 0.96-10.1 cm; P = .02).
      Side effects were worsening of acne and weight and muscle gain. CONCLUSIONS: In
      adolescents with Marfan syndrome, the accuracy and precision of 2 height
      prediction methods were limited. The apparent growth-reductive effect of sex
      hormone treatment appears similar to earlier reports on adolescents with
      constitutional tall stature. There were no clinically important short-term side
      effects.

PMID- 16291363
TI  - Cognitive functioning in children with early onset type 1 diabetes and severe
      hypoglycemia.
AB  - OBJECTIVE: To investigate whether severe hypoglycemia in young children with
      early-onset type 1 diabetes (T1DM) is associated with subsequent abnormalities in
      cognitive status. STUDY DESIGN: Recruitment was from a large population-based
      database of children and adolescents with T1DM. Children and adolescents with
      early-onset T1DM (<6 years) were eligible for the study. Diabetic individuals (n
      = 41) with a prospectively documented history of seizure or coma were compared
      with peers with no history of severe hypoglycemic events (n = 43). A
      comprehensive test battery of learning and memory was used together with
      intellectual and behavioral measures. RESULTS: No significant group differences
      were revealed on the intellectual, memory, or behavioral measures. Similarly,
      those participants with a history of early first seizure did not differ from
      their peers with no seizures. There were no significant group differences on the
      memory subtests that were examined given their potential sensitivity to
      compromised hippocampal function. CONCLUSIONS: There was no clear evidence from
      this cohort that episodes of seizure or coma, even those occurring in very early
      childhood, resulted in broad cognitive dysfunction, nor was there evidence of
      specific memory difficulties at the time of testing in children and adolescents
      with early-onset T1DM.

PMID- 16291364
TI  - Chronic lymphocytic meningitis in an adolescent.

PMID- 16291365
TI  - Identical phenotype in patients with somatic and germline CD95 mutations requires
      a new diagnostic approach to autoimmune lymphoproliferative syndrome.
AB  - In a patient with a somatic mutation in the CD95 gene, the long-term evolution of
      the clinical phenotype was indistinguishable from that of patients with
      autoimmune lymphoproliferative syndrome caused by germline CD95 mutations. A new
      diagnostic algorithm for autoimmune lymphoproliferative syndrome is suggested
      incorporating studies on sorted TCRalpha/beta+CD3+CD8-CD4- T cells.

PMID- 16291366
TI  - Serum prealbumin and albumin concentrations do not reflect nutritional state in
      children with cerebral palsy.
AB  - Serum prealbumin concentration (PALB) and albumin concentration (ALB) were
      evaluated as markers of undernutrition in 107 children with cerebral palsy (CP)
      age 2 to 18 years. PALB and ALB were rarely below the normal reference ranges and
      showed little to no correlation with anthropometric measures (eg, skinfolds,
      midarm fat area), growth (height), severity of CP (eg, feeding dysfunction, motor
      impairment), or general health.

PMID- 16291367
TI  - Feasibility of and delay in obtaining pulse oximetry during neonatal
      resuscitation.
AB  - Application of the sensor to newly born infants before connection to a pulse
      oximeter increases the reliability and speed with which data are displayed. Data
      are available in most infants within 90 seconds of birth. Oximetry may be useful
      in guiding interventions during resuscitation.

PMID- 16291368
TI  - Functional constipation in infants: a follow-up study.
AB  - Our objective of this study was to describe the clinical course of severe
      functional constipation in early childhood. Eligible patients were 47 children
      (60% boys; median age, 3.5 months) who had constipation in their first year of
      life. Follow-up data were obtained through a standardized questionnaire. Success
      was defined as a period of at least 4 weeks with > or =3 painless bowel movements
      per week. Six months after initial evaluation, 69% of the children were
      recovered. After initial success, a relapse occurred in 15% of the children
      within 3 years. A duration of symptoms <3 months before referral correlated
      significantly with better outcome. We conclude that most infants with severe
      constipation evaluated at a tertiary center are recovered after 6 months. Early
      therapeutic intervention may beneficially contribute to the resolution of
      constipation.

PMID- 16291370
TI  - A male infant with gynecomastia-galactorrhea.

PMID- 16291369
TI  - Phimosis: stretching methods with or without application of topical steroids?
AB  - Phimosis has been defined as unretractable foreskin without adherences or a
      circular band of tight prepuce preventing full retraction. We suggested a new
      treatment protocol combining betamethasone with stretching exercises to reduce
      the number of patients requiring surgery for phimosis. Between January 2003 and
      September 2004, 247 boys aged 4 to 14 years (mean 7.6) were included in this
      consecutive, prospective, open study. Patients were treated with 0.05%
      betamethasone cream applied to the distal aspect of the prepuce twice daily for
      the first 15 days, then once daily for 15 more days. Preputial gymnastics started
      1 week after topical application of betamethasone. Ninety-six percent of patients
      receiving 1 or more cycles of betamethasone showed complete resolution of
      phimosis. There was a significant difference (P < .001) in response rate between
      the study and control groups. Only 10 boys in the study group had no response to
      steroid and stretching. Treatment with topical steroids, combined with stretching
      exercises, is a suitable alternative to surgical correction (preputial
      plasty/circumcision).

PMID- 16291371
TI  - Diencephalic cachexia: a rare cause for failure to thrive.

PMID- 16291373
TI  - Antibiotic prescribing for upper respiratory tract infections in children: the
      role of parental expectations.

PMID- 16291374
TI  - Rituximab and factors predictive of response in chronic immune thrombocytopenic
      purpura of children.

PMID- 16291376
TI  - Thermal management of the extremely low birth weight infants at birth.

PMID- 16291379
TI  - Partnering with payers to improve surgical quality: the Michigan plan.

PMID- 16291381
TI  - Washington State's approach to variability in surgical processes/Outcomes:
      Surgical Clinical Outcomes Assessment Program (SCOAP).

PMID- 16291382
TI  - Surgeon compensation: "Pay for performance," the American College of Surgeons
      National Surgical Quality Improvement Program, the Surgical Care Improvement
      Program, and other considerations.

PMID- 16291383
TI  - The NSQIP: a new frontier in surgery.

PMID- 16291384
TI  - Dendritic cells as therapeutic adjuncts in surgical disease.

PMID- 16291385
TI  - How surgeons disclose medical errors to patients: a study using standardized
      patients.
AB  - BACKGROUND: Calls are increasing for physicians to disclose harmful medical
      errors to patients, but little is known about how physicians perform this
      challenging task. For surgeons, communication about errors is particularly
      important since surgical errors can have devastating consequences. Our objective
      was to explore how surgeons disclose medical errors using standardized patients.
      METHODS: Thirty academic surgeons participated in the study. Each surgeon
      discussed 2 of 3 error scenarios (wrong-side lumpectomy, retained surgical
      sponge, and hyperkalemia-induced arrhythmia) with standardized patients, yielding
      a total of 60 encounters. Each encounter was scored by using a scale developed to
      rate 5 communication elements of effective error disclosure. Half of the
      encounters took place face-to-face; the remainder occurred by videoconference.
      RESULTS: Surgeons were rated highest on their ability to explain the medical
      facts about the error (mean scores for the 3 scenarios ranged from 3.93 to 4.20;
      maximum possible score, 5). Surgeons used the word error or mistake in only 57%
      of disclosure conversations, took responsibility for the error in 65% of
      encounters, and offered a verbal apology in 47%. Surgeons acknowledged or
      validated patients' emotions in 55% of scenarios. Eight percent discussed how
      similar errors would be prevented, and 20% offered a second opinion or transfer
      of care to another surgeon. CONCLUSIONS: The patient safety movement calls for
      disclosure of medical errors, but significant gaps exist between how surgeons
      disclose errors and patient preferences. Programs should be developed to teach
      surgeons how to communicate more effectively with patients about errors.

PMID- 16291386
TI  - Inequity of upper gastrointestinal cancer distribution and survival with
      socioeconomic deprivation: a population-based study.
AB  - BACKGROUND: It is postulated that patients with upper gastrointestinal cancers
      from affluent classes have better survival outcomes than those from deprived
      backgrounds. We aimed to analyze the incidence, mortality, and survival trends of
      esophageal, gastric, and pancreatic cancers in West Midlands, England, from 1986
      to 2000 in terms of socioeconomic deprivation. METHODS: A well-validated
      demographic score, the Townsend Band, was employed as a measure of socioeconomic
      status. Data were collated from a cancer registry database; the individuals were
      allocated to 1 of 5 Townsend bands by using the postcodes at diagnosis. Relative
      survival rates were calculated by using stratified actuarial life tables,
      regression trend analysis at 1 and 5 years was performed, and the P value was
      derived from a t test statistic. RESULTS: An increase in esophageal cancer
      incidence was more marked in the affluent categories (127%), compared with the
      deprived categories (57%). Gastric cancer incidence fell preferentially by 31%
      and 47% in the most-deprived men and women, respectively, but remained relatively
      unchanged in the affluent groups. A marginal overall decrease in pancreatic
      cancer incidence masked preferential increases in the most-affluent men (39%) and
      women (41%). Small increases in 1- and 5-year survival were noted in affluent
      subgroups, with the 1-year survival advantage for esophageal cancer achieving
      significant levels in the most-affluent categories (P = .05). CONCLUSIONS: The
      esophageal cancer incidence increased preferentially in the affluent groups but
      with a marginally better survival rate. The gastric cancer incidence decreased
      noticeably in the most-deprived groups, suggesting that improvements in hygiene
      with consequent reduction in Helicobacter pylori primarily could be responsible.
      Pancreatic cancer trends were unrelated to social deprivation and warrant further
      studies.

PMID- 16291387
TI  - Superiority of postoperative epidural over intravenous patient-controlled
      analgesia in orthopedic oncologic patients.
AB  - BACKGROUND: Surgery for bone malignancy is associated with intense postoperative
      pain. Patient-controlled epidural analgesia (PCEA) and intravenous patient
      controlled analgesia (IV-PCA) are used currently for postoperative pain control.
      METHODS: The degree of pain control after resection of bone malignancy under
      combined general and epidural anesthesia followed postoperatively by
      prospectively randomized PCEA (ropivacaine 3.2 mg + fentanyl 8 microg/dose) or IV
      PCA (morphine 2 mg/dose) (n = 35/group) was assessed. Postoperative analgesia
      delivery continued for up to 96 h; intramuscular rescue with diclofenac 75 mg was
      also available. RESULTS: The mean hourly pain score among the PCEA patients was
      3.0 +/- 0.9, compared with 4. 7 +/- 0.6 (P < .01) among the IV-PCA patients. All
      mean hourly pain scores in the PCEA patients, except for the first 2 hours of
      treatment, were less than 4/10, but they were higher in the IV-PCA patients. The
      demand for diclofenac was 2 times (n = 10) lower for the PCEA patients, compared
      with their IV counterparts (n = 20, P < .01); the same difference applied to the
      overall side effects (n = 15 vs n = 30, P < .01). Self-rated wakefulness and
      feelings of well-being were better in the PCEA patients. CONCLUSIONS:
      Postoperative ropivacaine + fentanyl via PCEA reduces pain better and affords
      better subjective feelings than IV morphine via PCA after resection of bone
      malignancy carried out under combined general and epidural anesthesia.

PMID- 16291388
TI  - Obese teenagers treated by Lap-Band System: the Italian experience.
AB  - BACKGROUND: Little is known about obesity surgery in young and adolescent
      patients. The aim of this study is to evaluate results of laparoscopic adjustable
      gastric banding in obese teenagers. METHODS: Patients < or = 19 years old
      selected from the database of the Italian Collaborative Study Group for Lap-Band
      were analyzed according to mortality, comorbidities, laparotomic conversion,
      intra- and postoperative complications, body mass index (BMI), and % excess
      weight loss (EWL) at different times of follow-up. Data were expressed as mean +/
      SD. RESULTS: Fifty-eight (1.5%) of 3813 patients who underwent operation with
      the Lap-Band System were < or = 19 years old: 47F/11M; mean age, 17.96 +/- 0.99
      years (range, 15-19); mean BMI, 46.1 +/- 6.31 Kg/m2 (range, 34.9 - 69.25); mean %
      excess weight, 86.4 +/- 27.1 (range, 34 - 226.53). Sixteen (27.5%) of the 58
      patients were superobese (BMI > or = 50). In 27/58 (46.5%) patients, 1 or more
      comorbidities were diagnosed. Mortality was absent. Laparotomic conversion was
      necessary in 1 patient with gastric perforation on the anterior wall. Overall
      postoperative complications occurred in 6/58 (10.3%). The band was removed in
      6/58 (10.3%) patients for gastric erosion (3 patients), psychologic, intolerance
      (2 patients), and in the remaining patient was converted 2 years after surgery
      (BMI 31) to gastric bypass or gastric pouch dilatation. Patient follow-up at 1,
      3, 5, and 7 years was 48/52 (92.3%), 37/42 (88.1%), 25/33 (75.7%), and 10/10,
      respectively. At these times, mean BMI was 35.9 +/- 8.4, 37.8 +/- 11.27, 34.9 +/-
      12.2, and 29.7 +/- 5.2 Kg/m2. Mean %EWL at the same time was 45.6 +/- 29.6, 39.7
      +/- 29.8, 43.7 +/- 38.1, and 55.6 +/- 29.2. Five/25 (20%) patients had < or = 25%
      EWL at 5 years follow-up, while none of the 10 patients subject to follow-up at 7
      years had < or = 25% EWL. CONCLUSIONS: Lap-Band System is an interesting option
      for teenagers suffering obesity and its related comorbidities, which deserves
      further investigation.

PMID- 16291389
TI  - Thermoablation of colorectal liver metastases promotes proliferation of residual
      intrahepatic neoplastic cells.
AB  - BACKGROUND: Resection of liver neoplasms is believed to promote growth of
      residual intrahepatic neoplastic cells. As the effects of radiofrequency
      thermoablation (RFA) are still unknown, we aimed to compare the influence of RFA
      versus liver resection on residual intrahepatic neoplastic cells. METHODS: A
      primary metastasis was established by injection of syngenic CT-26 coloncarcinoma
      cells into the right liver lobe of Balb/C mice. Five days later, 3 x 10(5) GFP
      transfected CT-26 tumor cells were injected intraportally, and the primary
      metastasis was treated by resection (group I, n = 7) or RFA (group II, n = 7).
      The effect of resection/RFA on the growth of single intrahepatic GFP neoplastic
      cells was evaluated by intravital microscopy 7 days later. RESULTS: Resection of
      a primary metastasis enhanced the proliferation of residual intrahepatic
      neoplastic cells, compared with the control group. RFA led to an increased
      survival of residual neoplastic cells (5% +/- 2% vs 1% +/- 1% single cells) and
      significantly promoted the proliferation of neoplastic cells, compared with
      resection (13% +/- 4% vs 2% +/- 2% micrometastases). CONCLUSIONS: RFA strongly
      promotes intrahepatic growth of residual neoplastic cells. On the basis of our
      findings, RFA should not be recommended as an alternative curative treatment to
      resection. Furthermore, if RFA is performed as palliative therapy,
      postinterventional chemotherapy may be advisable to overcome the stimulation of
      residual neoplastic cells by RFA.

PMID- 16291390
TI  - Caroli's disease: liver resection and liver transplantation. Experience in 33
      patients.
AB  - BACKGROUND: The aim of this study was to review and discuss our observations on
      33 patients who underwent surgical treatment for Caroli's disease (CD), focusing
      on diagnosis, current surgical management, and long-term outcome. METHODS:
      Between May 1993 and June 2004, 642 liver resections and 286 liver
      transplantations in 252 patients were performed in our department of surgery.
      Thirty-three patients were referred to our center for diagnostic and therapeutic
      management of CD. Prior surgical interventions for hepatobiliary disorders,
      current diagnostic and surgical procedures, procedure-specific complications,
      duration of hospital stay, duration of follow-up, outpatient information, and
      long-term outcome were reviewed. RESULTS: Fifteen male and 18 female patients
      were treated in this study. Initial symptoms and signs of the disease noted in
      our patients included right upper quadrant pain, fever, and jaundice. In 2 of the
      33 patients, we noted clinical evidence of cirrhosis followed by histologic
      confirmation. One patient suffered from variceal bleeding. In 26 patients,
      diagnoses were established by a combined endoscopic retrograde
      cholangiopancreatography, ultrasonography, and computed tomographic studies. The
      disease was localized in 25 and diffuse in 8 patients. Liver resection was
      carried out in 29 patients. Partial hepatectomies were performed in 27 of these
      29 at our institution. Two female patients with the diffuse disease underwent
      orthotopic liver transplantation. Thirteen of the 31 patients who underwent
      surgery at our institution had an uneventful postoperative course. Fourteen
      patients had minor postoperative complications and responded well to medical
      management. Four patients had major complications that required further surgical
      treatment. Two patients died of complications related to postoperative hemorrhage
      and sepsis. Two patients with intrahepatic cholangiocarcinoma died because of
      primary tumor progress. One patient with cholangiocarcinoma died 1 year after a
      successful left hepatectomy because of metastatic disease recurrence. The long
      term results of the 26 surviving patients were assessed during a mean follow-up
      of 3.7 years (range, 1-11 years). All 26 patients remained free of biliary
      symptoms or complications. In 25 patients, surgery including liver
      transplantation was curative. CONCLUSIONS: Partial hepatectomy for localized CD
      is potentially curative. In patients with diffuse CD, liver transplantation
      provides gratifying long-term results.

PMID- 16291391
TI  - Intraoperative lymphatic mapping and sentinel lymph node biopsy using radioactive
      tracer in gastric cancer.
AB  - BACKGROUND: Gastric cancer continues to be a significant health problem around
      the world. Surgical resection with a lymph node dissection remains the only
      potentially curative treatment with gastric cancer. Determination of the extent
      of lymph node dissection required on the basis of actual node involvement in
      patients with gastric cancer is important as less extensive dissection may reduce
      postoperative morbidity and mortality rates. The current study examines the
      feasibility and reliability of sentinel lymph node biopsy in gastric cancer.
      METHODS: A total of 32 patients who underwent gastrectomy with extended
      lymphadenectomy were enrolled in this study. A total volume of 148 MBq (2 mL)
      technetium-99m-radiolabeled, filtered sulphur colloid solution was injected into
      the primary lesion under gastroscopy 2 hours before the operation. Lymph nodes
      were examined as soon as possible by a hand-held gamma probe during the
      operation, without significant manipulation of the stomach or greater omentum. A
      sentinel lymph node (SLN) was defined by a level of radioactivity 10 times higher
      than the background. RESULTS: Thirty-one of 32 patients had successful SLN
      biopsy, with a success rate of 97%. The sensitivity, specificity, positive
      predictive value, and negative predictive value of SLN biopsy were 100%, 95%,
      90%, and 100%, respectively. CONCLUSIONS: SLN biopsy using gamma probe in gastric
      cancer is a feasible procedure with high sensitivity and accuracy. This technique
      may be of a great benefit to surgeons in planning the extend of lymph node
      dissection in gastric cancer.

PMID- 16291392
TI  - Inhibition by nitric oxide and nonadrenergic, noncholinergic (NANC) nerves is
      preserved in a canine model of extrinsic denervation: implications for small
      bowel transplantation.
AB  - BACKGROUND: Small bowel transplantation (SBT) is complicated by changes in graft
      motility, especially in the early postoperative period. This dysmotility may be
      related in part to the extrinsic denervation necessitated by the procedure, but
      specific neurotransmitter response to SBT is incompletely understood. The aim of
      this study was to evaluate the role of nitric oxide and nonadrenergic,
      noncholinergic (NANC) enteric neural input in the nonimmunologic etiology of the
      dysmotility seen after SBT. METHODS: A technique of jejunoileal extrinsic
      denervation (without disruption of mesenteric vascular supply) was used as a
      model of canine jejunoileal autotransplantation to avoid potential confounding
      factors such as ischemia-reperfusion and postallotransplant immunologic effects.
      Longitudinal smooth muscle strips from ileum and jejunum were studied with in
      vitro tissue chamber methodology at 0, 2, and 8 weeks after this experimental
      model to explore early and late effects of denervation. Effects of exogenous
      nitric oxide (NO) and electric field stimulation (EFS), which releases native,
      endogenous enteric neurotransmitters) were evaluated in neurally intact control
      dogs and those undergoing extrinsic denervation. RESULTS: Exogenous NO caused a
      dose-dependent inhibition of spontaneous contractile activity and in some muscle
      strips a decrease in basal tone in both groups of dogs. These effects were
      unchanged by neural blockade with tetrodotoxin and preserved after extrinsic
      denervation. EFS produced inhibition of spontaneous contractile activity in ileum
      and a complex, inconsistent response in jejunum. The response to EFS in both
      ileum and jejunum was unchanged after extrinsic denervation. CONCLUSIONS: Nitric
      oxide inhibits contractile activity in canine longitudinal muscle of small bowel.
      Motility changes seen after this large animal model of extrinsic denervation are
      not caused by changes in NO or NANC neural function. The variability observed
      between different segments of intestine is important to consider in the context
      of SBT.

PMID- 16291393
TI  - Inhibition of tyrosine-kinase-mediated cellular signaling by tyrphostins AG 126
      and AG556 modulates murine experimental acute pancreatitis.
AB  - BACKGROUND: The effects of the tyrosine kinase inhibitors, tyrphostin AG126 and
      AG556 in a murine model of acute pancreatitis are investigated. METHODS:
      Intraperitoneal injection of cerulein in mice resulted in a severe, acute
      pancreatitis, which was characterized by edema, neutrophil infiltration, tissue
      hemorrhage, and cell necrosis as well as elevation in the serum activities of
      amylase or lipase. RESULTS: Infiltration of the pancreatic tissue of these
      animals with neutrophils (measured as increase in myeloperoxidase activity) was
      associated with signs of enhanced lipid peroxidation (increased tissue levels of
      malondialdehyde). Immunohistochemical examination showed a marked increase in
      immunoreactivity for nitrotyrosine and poly (ADP-ribose) polymerase (PARP) in the
      pancreas of cerulein-treated mice. Pretreatment or posttreatment with tyrphostin
      AG126 and AG556, 2 different tyrosine kinase inhibitors, significantly reduced
      the degree of pancreatic inflammation and tissue injury (histologic score). In
      particular, the treatment with the 2 tyrosine kinase inhibitors reduced the
      cerulein-induced nitrotyrosine formation and PARP activation in the pancreas as
      well as the systemic release of tumor necrosis factor alpha. CONCLUSIONS: This
      study provides the first evidence that (1) prevention of the activation of
      protein tyrosine kinases reduces the development of acute pancreatitis, and (2)
      inhibition of the activity of certain tyrosine kinases may represent a novel
      approach for the therapy of acute pancreatitis.

PMID- 16291394
TI  - Increased CDX2 and decreased PITX1 homeobox gene expression in Barrett's
      esophagus and Barrett's-associated adenocarcinoma.
AB  - BACKGROUND: The CDX2 (caudal-related homeobox gene 2) and PITX1 (pituitary
      homeobox 1) genes have essential roles in human development. Forced expression of
      Cdx2 alone in the murine stomach results in gastric intestinal metaplasia (IM).
      This study was undertaken to investigate the expression pattern of these critical
      morphogenesis genes in the Barrett's multistage carcinogenesis model. METHODS:
      CDX2 and PITX1 messenger RNA (mRNA) expression levels, relative to the control
      gene beta-actin, were measured by reverse transcription-polymerase chain reaction
      in specimens of Barrett's IM (n = 21), dysplasia (n = 18), adenocarcinoma (n =
      20), and matching normal squamous esophagus tissues (n = 39) collected from 19
      patients with Barrett's esophagus and 20 patients with esophageal adenocarcinoma.
      CDX2 protein expression was assessed by immunohistochemistry in specimens of
      normal squamous esophagus (n = 13), IM (n = 10), dysplasia (n = 8,) and
      adenocarcinoma (n = 5). RESULTS: The median relative CDX2 mRNA expression was
      approximately 200 times higher in Barrett's esophagus tissues (0.83) than in
      matching normal squamous esophagus (0.004) in the patients with Barrett's
      esophagus (P < .001). The mRNA expression in cancer tissues (0.49) was also
      higher than in matching normal squamous esophagus specimens (0.009, P < .001).
      There was no significant difference between the mRNA expression levels in
      Barrett's esophagus and adenocarcinoma. There was no CDX2 protein expression in
      normal squamous esophagus, but moderate to strong protein expression was seen in
      all Barrett's tissues and in a majority of the dysplasia and adenocarcinoma
      cells. Relative median PITX1 mRNA expression was decreased in Barrett's esophagus
      (8.02 for all specimens), compared with normal esophagus specimens (47.46 for all
      specimens, P < .001), and was further reduced in cancer specimens (2.21),
      compared with either Barrett's esophagus or normal esophagus (both P < .001).
      Wilcoxon testwas used for all P values shown. CONCLUSIONS: CDX2 mRNA and CDX2
      protein expression are upregulated in Barrett's IM tissues, compared with normal
      squamous esophagus, and remain elevated in dysplasia and adenocarcinoma tissues.
      In contrast, PITX1 mRNA expression is decreased in Barrett's esophagus, compared
      with matching normal squamous esophagus specimens, and is further decreased in
      Barrett's-associated cancer. These descriptive findings suggest a possible role
      for these genes in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence.

PMID- 16291395
TI  - Interleukin-1alpha-induced proteolytic activation of metalloproteinase-9 by human
      skin.
AB  - BACKGROUND: Increased activity of matrix metalloproteinase-9 (MMP-9) has been
      well documented in many diseases associated with inflammation, such as chronic
      wounds, bullous pemphigoid, liver failure, and tumor metastases. The mechanism
      for the proteolytic activation of pro-MMP-9 in human tissue still remains
      unknown. METHODS: We investigated this mechanism through reconstitution of an
      inflammatory condition in normal human skin, and epidermal and dermal cells
      derived from skin. Normal human skin was cultured with exogenous cytokines
      associated with inflammation and tissue repair. MMP-9 induction and activation
      were measured, and potential mechanisms were probed by inhibitors. RESULTS:
      Pathophysiologic concentrations of interleukin (IL)-1alpha rapidly induced pro
      MMP-9 synthesis by human skin. In contrast, IL-1-induced activation of pro-MMP-9
      was a slow process, which required 3 days. Tumor growth factor-beta induced pro
      MMP-9 but failed to promote activation of the precursor. When the skin was
      stimulated with the combination of tumor growth factor-beta and IL-1alpha,
      substantial induction and activation of pro-MMP-9 occurred. This IL-1 induced
      activation of pro-MMP-9 was observed in intact skin but not in isolated dermal
      fibroblasts or keratinocytes. IL-1-induced activation of pro-MMP-9 was inhibited
      by chymostatin, a chymotrypsinlike proteinase inhibitor. Furthermore, IL-1alpha
      decreased tissue inhibitor of metalloproteinase 1 without changing MMP-9
      activator activity. CONCLUSIONS: The proteolytic activation of pro-MMP-9 in skin
      inflammatory diseases likely occurs via a pathway including IL-1alpha. The
      activation is mediated by downregulation of tissue inhibitor of MMP-1 and
      involves an as yet unidentified chymotrypsinlike proteinase.

PMID- 16291397
TI  - A subsegmental pancreatectomy performed for carcinoma in situ limited to the
      proximal half of the pancreatic head with the aid of intraoperative 4-segment
      cytology for pancreatic juice--a case report.

PMID- 16291396
TI  - Adenoviral gene transfer of an NF-kappaB super-repressor increases collagen
      deposition in rodent cutaneous wound healing.
AB  - BACKGROUND: The transcription factor nuclear factor-kappaB (NF-kappaB) plays an
      essential role in inflammation. To date, no studies have investigated the effect
      of inhibiting NF-kappaB-mediated inflammation on normal cutaneous wound healing.
      We tested this by locally administering an adenovirus recombinant that
      constitutively expresses a super-repressor isoform of inhibitory-kappaB (IkappaB)
      into rats undergoing a well-established model of dorsal wound healing. METHODS:
      Seventy-two Sprague-Dawley rats underwent insertion of a sponge-pump construct
      into a dorsal subcutaneous pocket. One group of rats received pumps filled with
      the adenovirus expressing I-kappaB (rAd-Ikappab), a second group received pumps
      filled with adenovirus expressing green fluorescent protein (GFP) (rAd-gfp), and
      a third received pumps filled with normal saline (NS). Rats were killed in groups
      of 6 on days 1, 3, 5 and 7 postoperation. The wound fluid was analyzed for
      nitrite/nitrate (NOx) and tumor necrosis factor-alpha (TNF-alpha) concentrations.
      The wound fluid was assayed for hydroxyproline (OHP) content, an index of
      reparative collagen deposition. RESULTS: Administration of rAd-Ikappab for 7 days
      resulted in higher collagen deposition (OHP) compared with the rAd-gfp and NS
      groups. NOx levels were significantly higher in the rAd-gfp group on day 1 and
      marginally so on day 5. TNF-alpha quantitation analysis found no significant
      difference among the 3 groups. CONCLUSION: IkappaB expression through an
      adenoviral vector in the cutaneous wound may improve rodent healing, as shown by
      increased collagen deposition, through decreased inflammation. This mechanism
      appears to be TNF-alpha independent. Inhibition of NF-kappaB may reduce
      inflammation by reducing the local NOx concentrations.

PMID- 16291398
TI  - A simple modification with the Limberg flap for chronic pilonidal disease.

PMID- 16291399
TI  - Unexpected finding during inguinal hernia repair in a girl.

PMID- 16291400
TI  - Intestinal obstruction from furniture cushion foam bezoar.

PMID- 16291402
TI  - Idiopathic renal hypercalciuria as an etiology for persistent post-operative
      parathyroid hormone elevation.

PMID- 16291401
TI  - A little teaching point for the fellows...

PMID- 16291403
TI  - Pancreaticobiliary maljunction without choledochal dilatation associated with
      gallbladder cancer: report of 2 European cases.

PMID- 16291404
TI  - Long-term survival of pancreatic cancer patient diagnosed by positive telomerase
      activity of pancreatic juice.

PMID- 16291405
TI  - PCDDs, PCDFs and dioxin-like PCBs in food of animal origin (Slovakia).
AB  - The levels of 17 toxic polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs) and 12 non-ortho and mono-ortho polychlorinated biphenyls
      (PCBs) in 73 foodstuff samples of animal origin collected from shops and small
      farms in selected districts of Slovak Republic are presented in this paper. The
      concentrations expressed as WHO-TEQ in analysed samples ranged for PCDDs/PCDFs
      from 0.25 pg/g fat in pork to 75 pg/g fat in cod liver. The TEQ concentrations of
      non-ortho PCBs were between 0.007 and 181 pg/g fat and mono-ortho PCBs between
      0.0083 and 66.5 pg/g fat. The mean concentrations in freshwater fish and imported
      species of marine fish were 0.089 pg TEQ/g fresh weight for PCDDs/PCDFs, 0.17 pg
      TEQ/g fresh weight for non-ortho PCBs and 0.034 pg TEQ/g fresh weight for mono
      ortho PCBs. The mean total concentration of PCDDs/PCDFs and dioxin-like PCBs in
      samples of infant milk formula imported from EU countries was 0.98 pg TEQ/g fat.

PMID- 16291406
TI  - Priority organic pollutant assessment of sludges for agricultural purposes.
AB  - A comprehensive characterization of five of the seven priority organic pollutants
      listed in the draft of the "Working document on sludge" [EU, 2000. Working
      Document on Sludge 3rd Draft. Unpublished, 19 p] has been carried out during 2001
      2003 in sludge samples from Catalonia (NE Spain). One hundred and thirty-nine
      samples belonging to 20 Waste Water Treatment Plants (WWTPs), seven sludge
      treatment (thermal drying) and three composting sludge plants were taken in order
      to determine the concentration of polychlorinated dibenzo-p-dioxins and -furans
      (PCDD/Fs), di-2-(ethyl-hexyl)-phthalate (DEHP), nonylphenol and nonylphenol
      ethoxylates with one or two ethoxy groups (NPE), polycyclic aromatic hydrocarbons
      (PAHs) and polychlorinated biphenyls (PCBs). PCDD/F concentrations were in
      general lower than the 100 ng I-TEQ/kg limit suggested in the above-mentioned
      document. In the same way, 98.5% for PCBs, 97% for PAH and 92.8% for DEHP of the
      samples presented concentrations lower than 0.8 mg/kg dm, 6 mg/kg dm and 100
      mg/kg dm, respectively. In contrast, the vast majority of samples contained NPE
      concentrations much higher than 50mg/kg dm limit. The values ranged from 14.3 to
      3150 mg/kg dm (median value=286.6 mg/kg) being composted sludge samples the less
      contaminated ones (17.9-363.4 mg/kg dm; median value=89.3 mg/kg). Special
      attention should be paid to the Catalan sludge NPE contamination owing to the
      high levels detected.

PMID- 16291407
TI  - Structure selectivity in degradation and translocation of polychlorinated
      biphenyls (Delor 103) with a Pleurotus ostreatus (oyster mushroom) culture.
AB  - The biodegradation of polychlorinated biphenyls (PCBs), formerly applied in
      technical mixtures called Delor 103, was realized by the white rot fungus
      Pleurotus ostreatus. Besides the efficiency of degradation the translocation of
      PCBs into the fruit bodies grown during cultivation on straw were of special
      interest. The selectivity of PCBs degradation is discussed on the basis of
      structural features of the individual congeners. The most important structural
      factors affecting the degradation efficiency are indicated with molecular
      descriptors. Basic dependences of the degradation efficiency of congeners on
      their chlorination grade and ortho chlorosubstitution could be proved.
      Additionally, other structural parameters such as the number and position of non
      substituted carbon in the biphenyl molecule also affect the degradation results.
      Apart from the removal of Delor 103 the translocation of PCB isomers into the
      fruit bodies growing up during cultivation was observed. The structural features
      assisting the transport of PCB congeners from the straw substrate colonized with
      mushroom mycelium (straw/mycelium) to the mushroom fruit bodies are also relevant
      for the degradation mechanism but act reversely. Among the chlorination grade,
      structural parameters such as the number of para and adversely positioned
      chlorines or the number of occupied para and meta positions contribute to an
      accumulation of individual PCB congeners in the mushrooms. In total, only few PCB
      amounts (below 0.1% of the initially present PCBs in straw) were transported into
      the fruit bodies and a dangerous PCB contamination was never reached while the
      experiment. A combination of accelerated solvent extraction and GC-MS analysis
      was the analytical basis for the investigation presented.

PMID- 16291408
TI  - Incidence of infection during efalizumab therapy for psoriasis: analysis of the
      clinical trial experience.
AB  - BACKGROUND: Because many therapies for psoriasis disrupt the normal inflammatory
      cascade and could theoretically impair the body's ability to respond to external
      pathogens, a possible increase in the incidence of infection is a concern with
      any new psoriasis therapy that affects the immune system. Efalizumab is a
      biologic therapy targeted to inhibit T cells. Its efficacy has been shown in
      clinical trials encompassing >3500 patients with psoriasis. OBJECTIVES: The aims
      of this article were to review the incidence of infection observed in efalizumab
      treated patients during 12-week, Phase III clinical trials, compare the incidence
      rate with that in patients receiving placebo, and evaluate the incidence of
      infection observed in patients with extended (>12-week) efalizumab use. METHODS:
      Adverse events (AEs) of infection were tabulated from a pooled data set of 2335
      patients enrolled to receive 12 weeks of subcutaneous (SC) efalizumab 1 or 2
      mg/kg . wk or placebo in 4 randomized, double-blind, placebo-controlled, Phase
      III efalizumab clinical studies. The incidence of infection was further evaluated
      using pooled data from 1115 patients who received up to 24 weeks of efalizumab
      therapy during 5 clinical trials with treatment extension arms and from 170
      patients who received up to 108 weeks (27 months) of continuous therapy in an
      open-label, Phase III efalizumab trial of 36 months' total duration. RESULTS: The
      incidence and severity of AEs of infection during 12 weeks of efalizumab therapy
      were comparable to those observed in patients receiving placebo (overall, 28.6%
      vs 26.3%). Infections did not appear to increase with extended therapy of up to
      27 months. Serious infections requiring hospitalization occurred in 1.1% of
      efalizumab-treated patients. CONCLUSION: The present review of the available
      Phase III clinical trial suggests that efalizumab is not associated with an
      increased risk for infection in patients receiving initial or long-term (27
      month) treatment for moderate to severe chronic plaque psoriasis.

PMID- 16291409
TI  - Safety of doxycycline and minocycline: a systematic review.
AB  - OBJECTIVE: The goal of this review was to summarize the available literature
      covering the safety profiles of oral doxycycline and minocycline. METHODS:
      Scientific literature published between 1966 and August 2003 was searched using
      the MEDLINE, EMBASE, and Biosis databases (search terms: minocycline or
      doxycycline, each paired with adverse reaction, adverse event, and side effect,
      and doxycycline or minocycline with the limits English language, human, and
      clinical trials). Safety information was collected from case reports and clinical
      trials. Adverse event (AE) rates in the United States were calculated by
      comparing data from the MedWatch AE reporting program used by the US Food and
      Drug Administration (FDA) with the number of new prescriptions dispensed for each
      drug from January 1998 to August 2003. RESULTS: Between 1966 and 2003, a total of
      130 and 333 AEs were published in case reports of doxycycline and minocycline,
      respectively. In 24 doxycycline clinical trials (n = 3833) and 11 minocycline
      trials (n = 788), the ranges in incidence of AEs were 0% to 61% and 11.7% to
      83.3%, respectively. Gastrointestinal AEs were most common with doxycycline;
      central nervous system and gastrointestinal AEs were most common with
      minocycline. From January 1998 to August 2003, the FDA MedWatch data contained
      628 events for doxycycline and 1099 events for minocycline reported in the United
      States. Approximately 47,630,000 doxycycline and 15,234,000 minocycline new
      prescriptions were dispensed in the United States during that period, yielding
      event rates of 13 per million for doxycycline and 72 per million for minocycline,
      based on FDA data. CONCLUSIONS: Between 1998 and 2003, doxycycline was prescribed
      3 times as often as minocycline. The incidence of AEs with either drug is very
      low, but doxycycline had fewer reported AEs. Although more head-to-head clinical
      trials are needed for a direct comparison of AE frequency, these preliminary data
      from separate reports suggest the possibility that AEs may be less likely with
      doxycycline than minocycline.

PMID- 16291410
TI  - Pemetrexed: a multitargeted antifolate.
AB  - BACKGROUND: The US Food and Drug Administration approved pemetrexed in February
      2004 for the treatment of malignant pleural mesothelioma (MPM) in combination
      with cisplatin in patients with unresectable disease or for whom curative surgery
      is not an option. Pemetrexed is the first agent approved for the treatment of
      MPM. In August 2004, pemetrexed was approved as a second-line, single-agent
      treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC).
      OBJECTIVES: The goals of this article were to summarize the pharmacology,
      pharmacokinetics, efficacy, and safety of pemetrexed, and to review its current
      and potential roles in therapy for MPM, NSCLC, and other oncologic conditions.
      METHODS: Relevant English-language literature was identified through searches of
      PubMed (1966-December 2004), International Pharmaceutical Abstracts, and the
      Proceedings of the American Society of Clinical Oncology (January 1995-December
      2004). Search terms included pemetrexed, Alimta, MTA, multitargeted antifolate,
      LY231514, mesothelioma, MPM, non-small cell lung cancer, NSCLC, breast cancer,
      and pancreatic cancer. In addition to published literature, abstracts and posters
      presented at national and international scientific meetings were reviewed.
      RESULTS: Myelosuppression was the predominant dose-limiting toxicity of
      pemetrexed reported in Phase I studies. Identification of the correlation between
      poor folate status and increased pemetrexed toxicity in a multivariate analysis
      led to the requirement of folic acid and vitamin B12 supplementation for patients
      in all pemetrexed studies, with a resulting noted decrease in pemetrexed
      toxicity. A single, multicenter, randomized Phase III trial compared the efficacy
      of pemetrexed in combination with cisplatin versus cisplatin alone in the
      treatment of MPM. Response rates were 41.3% in the pemetrexed/cisplatin
      combination and 16.7% with single-agent cisplatin (P < 0.001). The median
      survival time for the pemetrexed/cisplatin combination was significantly longer
      at 12.1 months versus 9.3 months for cisplatin alone (P = 0.02). One
      international, multicenter, randomized Phase III trial in patients with NSCLC
      compared single-agent pemetrexed versus docetaxel in patients previously treated
      with chemotherapy. Overall response rates (9.1% and 8.8%) and median survival
      (8.3 months and 7.9 months) did not differ between pemetrexed and docetaxel (P =
      0.105 and P = 0.226, respectively). Hematologic adverse effects-grade 3/4
      neutropenia (40.2% vs 5.3%; P < 0.001), febrile neutropenia (12.7% vs 1.9%; P <
      0.001), and neutropenic infections (3.3% vs 0%; P = 0.004)-were significantly
      greater in the docetaxel-treated patients than in the pemetrexed-treated
      patients, as was alopecia (37.7% vs 6.4%; P < 0.001). Results of an
      international, multicenter Phase III trial of pemetrexed in combination with
      gemcitabine conducted in patients with pancreatic cancer indicate that the
      combination is no more efficacious than single-agent gemcitabine. Results in
      other disease states are still preliminary. CONCLUSIONS: Pemetrexed is a
      multitargeted antifolate that has demonstrated antitumor activity in various
      tumor types as a single agent and in combination with other chemotherapeutic
      agents. Efficacy for the treatment of MPM in combination with cisplatin has been
      demonstrated, and approval as a second-line agent in NSCLC was based on response
      rate as a surrogate end point for survival. The addition of folic acid and
      vitamin B12 supplementation markedly reduced.

PMID- 16291411
TI  - Long-term effects of glimepiride or rosiglitazone in combination with metformin
      on blood pressure control in type 2 diabetic patients affected by the metabolic
      syndrome: a 12-month, double-blind, randomized clinical trial.
AB  - BACKGROUND: Some evidence suggests that antihyperglycemic drugs might have a
      small but clinically significant beneficial effect on blood pressure in patients
      with diabetes mellitus. Based on a literature search, few direct comparisons of
      different antihyperglycemic treatments on blood pressure have been reported.
      OBJECTIVES: The primary aim of the present study was to compare the effect of
      long-term (12-month) combination treatment with glimepiride or rosiglitazone plus
      metformin on blood pressure in patients with type 2 diabetes mellitus (DM-2) and
      the metabolic syndrome. Secondary end points were glycemic control and
      improvement in insulin sensitivity. METHODS: This randomized, double-blind study
      was conducted at 2 centers in Italy. Patients aged > or =18 years with DM-2 and
      the metabolic syndrome and poor glycemic control (insulin resistance) with
      monotherapy with the maximum tolerated dose of an antihyperglycemic agent (eg, a
      sulfonylurea, metformin) were enrolled. All patients received 12 months of oral
      treatment with metformin 500 mg TID plus glimepiride 2 mg QD (G + M) or
      rosiglitazone 4 mg QD (R + M). Blood pressure, heart rate (HR), and body mass
      index (BMI); plasma levels of fasting and postprandial glucose and insulin (FPG,
      PPG, FPI, and PPI, respectively) and glycosylated hemoglobin (HbA(1c)); and
      homeostasis model assessment (HOMA) index were determined at 0 (baseline), 3, 6,
      9, and 12 months of treatment. Adverse effects (AEs) were assessed using
      spontaneous reporting, patient interview, and laboratory analysis. RESULTS:
      Ninety-nine patients were enrolled in the study; 95 completed it (48 men, 47
      women; mean age, 54 years [range, 47-58 years]; G + M, 47 patients; R + M, 48
      patients). Four patients did not complete the study due to noncompliance (2
      patients in the R + M group), protocol violation (1 patient in the G + M group),
      and loss to follow-up (1 patient in the G + M group). Mean blood pressure values
      were not significantly improved in the G + M group at any time point, whereas
      these values were significantly improved at 12 months in the R + M group. Mean
      BMI, HbA(1c), FPG, and PPG were significantly decreased from baseline in both
      groups at 12 months (all, P < or = 0.05). Mean FPI, PPI, and HOMA index were
      significantly improved at 12 months only in the R + M group (all, P < or = 0.05
      vs baseline); these changes were not found in the G + M group. No significant
      changes in HR were found. Headache and flatulence were reported in both groups (G
      + M, 2 patients each; R + M, 1 and 2 patients, respectively), but these AEs were
      mild and transient. In the R + M group, liver enzyme levels were increased to 1.5
      fold the upper limit of normal in 3 patients, but were normalized by study end.
      CONCLUSIONS: In this study in patients with DM-2 and the metabolic syndrome, long
      term (12-month) combination treatment with R + M, but not G + M, was associated
      with a significant improvement in blood pressure control. Improvements in
      glycemic control and insulin resistance-related parameters were found at 9 months
      with R + M, compared with 12 months with G + M. Both treatments were well
      tolerated.

PMID- 16291412
TI  - Comparison of the effects of ketotifen fumarate 0.025% and olopatadine HCl 0.1%
      ophthalmic solutions in seasonal allergic conjunctivities: a 30-day, randomized,
      double-masked, artificial tear substitute-controlled trial.
AB  - BACKGROUND: Topical antiallergic agents, such as antihistamines and mast-cell
      stabilizers, are the main therapeutic options for seasonal allergic
      conjunctivitis (SAC). Ketotifen fumarate and olopatadine HCl have dual action
      that offers a combination of these 2 mechanisms. Although clinical studies
      comparing the efficacy of these 2 drugs have shown that both were effective in
      the treatment of SAC, the results were contradictory and did not include the
      effects of these drugs on inflammatory markers. OBJECTIVES: The aims of this
      study were to compare the clinical efficacy of topical ketotifen and olopatadine
      eye drops and to determine the effects of these 2 drugs on the expression of cell
      adhesion molecules (CAMs) and inflammatory markers in conjunctival surface cells
      in patients with SAC. METHODS: This 30-day, randomized, double-masked, artificial
      tear substitute (ATS)-controlled clinical trial was conducted at the Department
      of Ophthalmology, Karadeniz Technical University, School of Medicine, Trabzon,
      Turkey. Patients with SAC were included in the study and randomly assigned to 1
      of 3 groups: topical ketotifen fumarate 0.025% ophthalmic solution, topical
      olopatadine HCl 0.1% ophthalmic solution, or ATS (control group). All drugs were
      administered 2 drops per eye BID for 30 days. At the beginning of the study (day
      0; baseline), on day 15, and on day 30, clinical scores (itching, tearing,
      redness, eyelid, swelling, and chemosis) and conjunctival impression cytology
      specimens were obtained. The percentages of cells expressing intercellular
      adhesion molecule 1, vascular CAM-1, human leukocyte antigen-DR, and beta1
      integrin (CD29) from conjunctival impression cytology specimens were determined
      using flow cytometry. Patients were questioned about adverse events (AEs) at each
      visit. Ocular discomfort on installation of the drugs was recorded as an AE.
      RESULTS: Thirty-nine patients (20 men, 19 women; age range, 18-61 years) with SAC
      were included. Twelve patients received ketotifen; 13, olopatadine; and 14, ATS.
      In both active-treatment groups, the improvements of clinical scores (tearing and
      itching) were more pronounced compared with those in the ATS group, although the
      day-30 difference in tearing score between the olopatadine and ATS groups was not
      statistically significant. No significant within-group or between-group
      differences in mean scores for redness, chemosis, or eyelid swelling were found.
      The expression rates of CAMs and inflammatory markers in conjunctival surface
      cells were significantly more reduced with ketotifen and olopatadine compared
      with ATS. However, clinical and flow cytometric parameters were improved with ATS
      at 15 and 30 days compared with baseline. No AEs were observed during the study
      period. CONCLUSIONS: In this short-term study in a selected, small study
      population with SAC, ketotifen and olopatadine diminished the expression of CAMs
      and inflammatory markers on the conjunctival surface cells effectively. Both
      active treatments were more efficacious compared with ATS and were well
      tolerated.

PMID- 16291413
TI  - Pharmacokinetic interaction of solifenacin with an oral contraceptive containing
      ethinyl estradiol and levonorgestrel in healthy women: a double-blind, placebo
      controlled study.
AB  - BACKGROUND: Solifenacin succinate (YM905; Vesicare, Astellas Pharma Inc., Tokyo,
      Japan) is a new once-daily, orally administered muscarinic receptor antagonist
      under investigation for the treatment of overactive bladder. OBJECTIVE: The aim
      of this study was to evaluate the effect of solifenacin on the pharmacokinetic
      (PK) parameters of an oral contraceptive (OC) containing ethinyl estradiol (EE)
      and levonorgestrel (LNG). METHODS: In a double-blind, placebo-controlled, 2
      period, crossover study, 24 healthy, young, white women received a combined OC
      (EE 30 microg + LNG 150 microg) daily for two 21-day cycles, separated by a 7-day
      washout. On day 12 of each cycle, subjects began a 10-day regimen of solifenacin
      10 mg QD, which is 2 times the suggested starting dose, or placebo. Subjects
      crossed over to the other treatment arm for the second cycle. Primary PK end
      points were C(max) and AUC from time 0 to 24 hours (AUC(0-24 h)) for EE and LNG.
      Women ranged in age from 20 to 37 years and had a mean body weight of 64 kg, mean
      height of 167.4 cm, and mean body mass index of 23 kg/m2. Seven women had never
      smoked, while 5 were former smokers and 12 were regular smokers. Safety
      assessments included the nature, frequency, and severity of spontaneously
      reported or observed adverse events, vital signs, electrocardiogram, laboratory
      values, and physical examination. RESULTS: Statistical analysis of AUC(0-24
      h)/product of baseline concentration and total blood sampling time, and
      C(max)/baseline concentration ratios of solifenacin versus placebo for EE and LNG
      found the 90% CI to be within the predefined range of 0.8 to 1.25 (EE: 0.854
      1.164 and 0.822-1.167; LNG: 0.920-1.125 and 0.910-1.139). The number of samples
      with non-quantifiable luteinizing hormone (LH) and folliclestimulating hormone
      (FSH) levels were comparable after administration of the OC with either
      solifenacin or placebo. The adverse event most frequently reported was dry mouth
      (solifenacin, n = 25 [9 mild, 13 moderate, and 3 severe] vs placebo, n = 1
      [moderate]). There were no clinically relevant effects on vital signs,
      electrocardiogram, or laboratory parameters. CONCLUSIONS: A PK interaction
      between solifenacin and the OC containing EE and LNG was not found in this study.
      Solifenacin was not found to have altered suppression of LH or FSH. The drug was
      well tolerated in these healthy, young, white, adult female volunteers.

PMID- 16291414
TI  - Dexamethasone-eluting stents and plasma concentrations of adhesion molecules in
      patients with unstable coronary syndromes: results of the historically controlled
      SESAME study.
AB  - BACKGROUND: Plasma concentrations of intercellular adhesion molecule-1 [ICAM-1],
      vascular cell adhesion molecule-1 [VCAM-1], and E-selectin may increase after
      percutaneous coronary intervention (PCI). OBJECTIVE: The aim of this study was to
      assess whether anti-inflammatory treatment with steroid-eluting stents influenced
      concentrations of adhesion molecules after PCI in patients with unstable coronary
      syndromes. METHODS: Consecutive patients with unstable coronary syndromes who
      were prospectively assigned to undergo implantation of a dexamethasone-eluting
      stent were compared with a control group of consecutive historical patients who
      received a similar non-drugeluting stent in the period immediately preceding
      availability of the steroid-eluting stents. Circulating concentrations of
      adhesion molecules were measured before the procedure and at 6 and 24 hours after
      implantation. RESULTS: The study included 50 patients who received the
      dexamethasone-eluting stent (41 men, 9 women; mean [SD] age, 60 [9] years) and 50
      historical controls who received the non-drug-eluting stent (40 men, 10 women;
      mean age, 63 [11] years). Baseline values for the adhesion molecules were similar
      in the 2 groups: in patients who received the dexamethasone-eluting stent, mean
      (SD) values were 210 (41) ng/mL for ICAM-1, 637 (119) ng/mL for VCAM-1, and 46
      (9) ng/mL for E-selectin; in the control group, the corresponding values were 218
      (42), 618 (140), and 43 (10) ng/mL. Circulating concentrations at 24 hours were
      significantly lower in patients receiving the drug-eluting stent compared with
      controls for both ICAM-1 (279 [49] vs 338 [60] ng/mL, respectively; P = 0.001)
      and VCAM-1 (772 [163] vs 896 [207] ng/mL; P = 0.004). There was no significant
      between-group difference in E-selectin concentrations at 24 hours (60 [10] vs 56
      [11] ng/mL). CONCLUSION: In this study, dexamethasone-eluting stents reduced
      plasma concentrations of ICAM-1 and VCAM-1 after PCI in patients with unstable
      coronary syndromes compared with historical controls.

PMID- 16291415
TI  - Safety and effectiveness of topiramate for the management of painful diabetic
      peripheral neuropathy in an open-label extension study.
AB  - OBJECTIVE: The aim of this study was to further assess the long-term safety and
      effectiveness of open-label topiramate therapy in subjects with moderately to
      severely painful diabetic peripheral neuropathy (DPN). METHODS: Adults aged 18 to
      75 years received open-label topiramate (25-600 mg/d for 26 weeks) in an
      extension of a previously published randomized, double-blind trial comparing
      topiramate with placebo. Safety analyses included adverse event (AE) reports and
      clinical laboratory tests. Metabolic end points included body weight and
      glycosylated hemoglobin (HbA(1c)). Effectiveness analyses included a 100-mm pain
      visual analog (PVA) scale, worst and current pain severity, and sleep disruption.
      RESULTS: Two hundred five subjects participated in this open-label extension
      study (118 formerly treated with topiramate and 87 who formerly received
      placebo). The groups did not differ in baseline demographics or disease
      characteristics. One hundred twenty-four (60.5%) subjects (68.6% of former
      topiramate recipients and 49.4% of former placebo recipients) completed the
      extension study; the most common reason for discontinuation was an AE (27.3% of
      subjects). AEs among subjects who received > or =1 dose of topiramate (n = 298)
      included upper respiratory tract infection (16.1%), anorexia (15.1%), diarrhea
      (12.8%), nausea (12.8%), paresthesia (10.7%), and headache (10.1%). Baseline pain
      scores were lower in those formerly treated with topiramate (n = 117) than in the
      former placebo group (n = 86) (PVA: 43.3 vs 52.5, P = 0.014; worst pain: 1.9 vs
      2.5, P < 0.001; current pain: 1.6 vs 1.9, P = 0.026; sleep disruption: 3.6 vs
      4.6, P = 0.021). At the final visit, PVA, current pain, and sleep disruption
      scores were not significantly different between the former topiramate and former
      placebo groups, but worst pain differed significantly (1.4 vs 1.8; P = 0.025).
      Mean weight loss from the start of topiramate therapy was 5.2 and 5.3 kg in the
      former topiramate and former placebo groups, respectively (P < 0.001 vs
      baseline). Mean HbA(1c) values before and after topiramate treatment were 7.7%
      and 7.4%, respectively, in the former topiramate group (P = 0.004 vs baseline),
      and 7.6% and 7.1%, respectively, in the former placebo group (P < 0.001 vs
      baseline). CONCLUSION: Although 39.5% of subjects discontinued, most often due to
      AEs, the results of this 26-week, open-label extension study with topiramate (up
      to 600 mg/d) in subjects with moderately to severely painful DPN suggest that
      pain relief was effective and durable.

PMID- 16291416
TI  - Efficacy and safety of biphasic insulin aspart 30 combined with pioglitazone in
      type 2 diabetes poorly controlled on glibenclamide (glyburide) monotherapy or
      combination therapy: an 18-week, randomized, open-label study.
AB  - BACKGROUND: Few large randomized controlled trials have assessed the value of
      adding insulin to an oral antidiabetic drug regimen. OBJECTIVE: This trial
      compared the efficacy and safety of biphasic insulin aspart 30/70 (BIAsp 30) plus
      pioglitazone (n = 93), glibenclamide (glyburide) plus pioglitazone (n = 91), or
      BIAsp 30 monotherapy (n = 97). METHODS: This 18-week, multinational, multicenter,
      randomized, open-label, parallel-group trial involved 281 patients with type 2
      diabetes (60% male; mean age, 56 years; mean body mass index, 29.5 kg/m2) with
      inadequate glycemic control (mean glycosylated hemoglobin [HbA(1c)], 9.5%; range,
      7.4%-14.7%) on glibenclamide monotherapy or combination therapy. The primary
      objective was to compare end-of-trial HbA(1c) among the 3 treatment groups.
      Fasting and mean 7- and 8-point blood glucose profiles, blood lipid levels,
      plasminogen activator inhibitor levels, adverse events, and hypoglycemia
      frequency were also compared. Patients using BIAsp 30 (alone or with
      pioglitazone) were injected twice daily (immediately before breakfast and
      dinner). Pioglitazone (30 mg/d) and glibenclamide (5-15 mg/d) were taken orally
      once daily with or immediately after breakfast. RESULTS: At the end of the trial,
      HbA(1c) was significantly lower for the BIAsp 30 plus pioglitazone group than for
      the glibenclamide plus pioglitazone group (mean [SD], -0.64% [0.23%]; P = 0.005)
      and the BIAsp 30 monotherapy group (-0.60% [0.22%]; P = 0.008). Mean (SD) fasting
      blood glucose (before breakfast) was significantly lower for BIAsp 30 plus
      pioglitazone than for glibenclamide plus pioglitazone (153 [45] mg/dL vs 169 [65]
      mg/dL, respectively; P = 0.012). Each time point on the 8-point blood glucose
      profile was lower for BIAsp 30 plus pioglitazone than for glibenclamide plus
      pioglitazone (P < 0.001 to P < 0.05). No major hypoglycemic episodes were
      reported, and the absolute rate of hypoglycemic events was low (<1 event/patient
      week) in the BIAsp-only group. Edema was reported in < or =9% of patients in each
      treatment group, but no occurrence was classified as serious. Weight gain (mean,
      4.0 kg) was more common in the BIAsp plus pioglitazone group (8%); however, this
      was consistent with improved glycemic control and is similar to that reported in
      other pioglitazone trials. CONCLUSIONS: BIAsp 30 plus pioglitazone provided an
      efficacious and well-tolerated treatment alternative to glibenclamide plus
      pioglitazone or BIAsp 30 alone in this population of patients who previously were
      not well controlled on glibenclamide monotherapy or combination therapy.

PMID- 16291417
TI  - In vitro and in vivo evaluation of enoxaparin removal by continuous renal
      replacement therapies with acrylonitrile and polysulfone membranes.
AB  - BACKGROUND: Enoxaparin is a low-molecular-weight heparin for which the degree of
      elimination through hemofilters during continuous renal replacement therapy
      (CRRT) is not well established. OBJECTIVE: The elimination of enoxaparin by CRRT,
      using acrylonitrile (AN69) or polysulfone (PS) membranes, was studied in vitro
      and among critically ill patients. METHODS: In vitro procedures were carried out
      using Ringer's lactate, bovine albumin-containing Ringer's lactate, or fresh
      human plasma as enoxaparin vehicle, using AN69 or PS membranes, and following
      continuous veno-venous hemofiltration (CVVH) or continuous veno-venous
      hemodialysis (CVVHD). Prefilter and ultrafiltrate samples were collected over 60
      minutes. All procedures were carried out in triplicate. Patients undergoing CRRT
      entered the in vivo study. Enoxaparin was administered subcutaneously once daily.
      The sieving coefficient (Sc) and saturation coefficient (Sa) were calculated as
      the relation between anti-factor Xa activity in simultaneously collected
      dialysate/ultrafiltrate samples and plasma samples. RESULTS: Mean Sc (for CVVH)
      or Sa (for CVVHD) values in the in vitro procedures ranged from 0.16 to 0.57. Sc
      values during CVVH were significantly higher than Sa values during CVVHD in the
      Ringer's lactate procedures for both membranes (AN69 membrane, P = 0.014; PS
      membrane, P < 0.001) and in the plasma procedures with the PS membrane (P <
      0.001). Six male and 2 female patients (all white) participated in the in vivo
      study. Their mean body weight ranged from 55 to 80 kg, and their age ranged from
      71 to 82 years. In patients, Sc or Sa achieved values between 0.26 and 0.67. No
      significant differences were found in vivo in the permeability of the 2 membranes
      to enoxaparin. CONCLUSIONS: In these studies, the Sc and Sa values suggested that
      enoxaparin passed through AN69 and PS membranes during CRRT. Further
      pharmacokinetic and clinical studies are needed to determine whether a dose
      adjustment for enoxaparin is needed for patients undergoing CRRT.

PMID- 16291418
TI  - Erectile response to vardenafil in men with a history of nonresponse to
      sildenafil: a time-from-dosing descriptive analysis.
AB  - BACKGROUND: The efficacy and tolerability of vardenafil hydrochloride in men with
      erectile dysfunction (ED) and a history of nonresponse to sildenafil citrate have
      previously been reported. OBJECTIVE: The aim of this descriptive analysis was to
      assess the efficacy and tolerability of vardenafil at various times after dosing
      in men with ED and a history of nonresponse to sildenafil and who chose to
      attempt sexual intercourse between 0.25 and 6 hours after dosing with vardenafil.
      METHODS: This analysis used data from a previously published 12-week,
      prospective, randomized, double-blind, flexible-dose, placebo-controlled study
      conducted at 41 hospitals and outpatient clinics across Australia, Europe, Asia,
      and North America. In that study, men with ED and sildenafil nonresponse, defined
      using 6 rigorous criteria (including nonresponse to the highest recommended dose,
      100 mg/d) were assigned to receive vardenafil 10 mg or placebo QD. At study weeks
      4 and 8, patients in both groups were given the option to maintain the 10-mg/d
      dose, or have the dose titrated to 5 or 20 mg/d. The present analysis used data
      from patient diaries completed daily, which included information concerning
      attempts at sexual intercourse, time from dosing to attempt, penetration, and
      maintenance of erection sufficient for successful intercourse. At week 12, diary
      data were categorized into time intervals (in hours) after dosing. For each
      interval, the per-patient success rate was based on the total number of attempts
      made in that interval. Comparative statistics were not performed on the time
      interval analysis. Tolerability was monitored throughout the study. Data
      concerning the primary end point were reported previously. RESULTS: A total of
      463 men were enrolled, of whom 457 were included in the safety analysis
      (vardenafil, n = 231; placebo, n = 226) and 454 in the intent-to-treat analysis
      (vardenafil, n = 229; placebo, n = 225; mean age, 60.1 vs 59.0 years; mean body
      mass index, 28.7 vs 28.0 kg/m2). Six patients were excluded from the safety
      analysis (2 patients did not use study medication [placebo group], postbaseline
      safety data unavailable in 4 patients [2 in each study group]). Men receiving
      vardenafil had numerically greater penetration and completion success rates
      compared with those receiving placebo at all time intervals. Penetration success
      rates were numerically higher with vardenafil compared with placebo as early as
      within 0.25 hour after dosing (62% vs 30%); efficacy continued beyond 6 hours
      after dosing in 77% and 50% of patients, respectively. Similarly, vardenafil
      treated patients had numerically greater completion success rates compared with
      those receiving placebo at 0.25 hour (53% vs 12%) and beyond 6 hours after dosing
      (70% vs 24%). The most common drug-related adverse events in the vardenafil and
      placebo groups were flushing (7% vs 1%), headache (6% vs 2%), and nasal
      congestion (5% vs <1%). CONCLUSIONS: This descriptive analysis suggests that
      erection sufficient for penetration and intercourse completion was achieved
      within 0.25 hour and lasted for >6 hours after dosing with vardenafil 10 mg in
      these men with mostly moderate to severe ED and a history of nonresponse to
      sildenafil and who chose to make attempts during those intervals. The drug was
      generally well tolerated.

PMID- 16291419
TI  - Public-private arrangements in disaster relief and recovery.

PMID- 16291420
TI  - A cost-effectiveness analysis of fluvastatin in patients with diabetes after
      successful percutaneous coronary intervention.
AB  - BACKGROUND: The Lescol Intervention Prevention Study (LIPS) was a multinational
      randomized controlled trial that showed a 47% reduction in the relative risk of
      cardiac death and a 22% reduction in major adverse cardiac events (MACEs) from
      the routine use of fluvastatin, compared with controls, in patients undergoing
      percutaneous coronary intervention (PCI, defined as angioplasty with or without
      stents). In this study, MACEs included cardiac death, nonfatal myocardial
      infarction, and subsequent PCI and coronary artery bypass graft. Diabetes was the
      greatest risk factor for MACEs. OBJECTIVE: This study estimated the cost
      effectiveness of fluvastatin when used for secondary prevention of MACEs after
      PCI in people with diabetes. METHODS: A post hoc subgroup analysis of patients
      with diabetes from the LIPS was used to estimate the effectiveness of fluvastatin
      in reducing myocardial infarction, revascularization, and cardiac death. A
      probabilistic Markov model was developed using United Kingdom resource and cost
      data to estimate the additional costs and quality-adjusted life-years (QALYs)
      gained over 10 years from the perspective of the British National Health Service.
      The model contained 6 health states, and the transition probabilities were
      derived from the LIPS data. Crossover from fluvastatin to other lipid-lowering
      drugs, withdrawal from fluvastatin, and the use of lipid-lowering drugs in the
      control group were included. RESULTS: In the subgroup of 202 patients with
      diabetes in the LIPS trial, 18 (15.0%) of 120 fluastatin patients and 21 (25.6%)
      of 82 control participants were insulin dependent (P = NS). Compared with the
      control group, patients treated with fluvastatin can expect to gain an additional
      mean (SD) of 0.196 (0.139) QALY per patient over 10 years (P < 0.001) and will
      cost the health service an additional mean (SD) of 10 pounds ( 448 pounds) (P =
      NS) (mean [SD] US $16 [$689]). The additional cost per QALY gained was 51 pounds
      (US $78). The key determinants of cost-effectiveness included the probabilities
      of repeat interventions, cardiac death, the cost of fluvastatin, and the time
      horizon used for the evaluation. CONCLUSION: Fluvastatin was an economically
      efficient treatment to prevent MACEs in these patients with diabetes undergoing
      PCI.

PMID- 16291421
TI  - Factors influencing the shift of patients from one proton pump inhibitor to
      another: the effect of direct-to-consumer advertising.
AB  - BACKGROUND: Switching from one proton pump inhibitor (PPI) to another is common,
      and may be related to factors other than efficacy and tolerability. OBJECTIVES:
      The purposes of this study were to describe the incidence of therapeutic
      switching among PPI users, quantify direct ambulatory medical costs of switching,
      and characterize the relationship between product switching and variables
      hypothesized to influence a switch (eg, direct-to-consumer [DTC] advertising,
      structure of insurance coverage, disease diagnosis). METHODS: This was a
      retrospective cohort study of health plans using 1998 data. The subjects were
      employees and dependents with employer-sponsored health insurance contributing to
      the Medstat Market-Scan administrative dataset. Using a commercially available
      database to quantify DTC advertising by marketing area, market-specific
      expenditures were matched to eligible subjects. Among PPI users, we identified
      those who switched from one product to another (switchers) and compared their
      utilization and spending with nonswitchers. We then evaluated the relationship
      between drug use and variables hypothesized to affect switching: DTC advertising,
      insurance characteristics, patient diagnosis, diagnostic procedures,
      comorbidities, age, and sex. RESULTS: The analysis used data for 396,500
      individuals from 47 unique markets that were geographically well distributed,
      with population density similar to that of the United States overall. The sample
      was also comparable with US census estimates for age and sex among working adults
      and their dependents. Only 620 (6.3%) of PPI users switched products during the
      1998 calendar year. Annual diagnostic and drug costs were >US $400 higher for
      switchers than nonswitchers. Subjects in areas with high levels of DTC
      advertising were 43% more likely to switch from lansoprazole to omeprazole than
      those in the low-expenditure areas. Additionally, patients paying prescription
      drug copayments >US $5 were 12% less likely to switch from lansoprazole to
      omeprazole than patients paying lower copayments. CONCLUSIONS: In these privately
      insured patients using PPIs, product switching was associated with increased
      treatment costs. DTC advertising and patient cost-sharing were important
      predictors of product switching.

PMID- 16291423
TI  - Improving outcomes in the treatment of locally-advanced NSCLC with gemcitabine.
AB  - Multiple approaches of combined modality therapy have emerged as potential
      treatments for improving unresectable, locoregionally advanced non-small-cell
      lung cancer (NSCLC). Several agents have been used either sequentially or
      concurrently in clinical trials of combined chemoradiotherapy. However, no
      specific regimen has been clearly defined, particularly with regard to the timing
      of chemotherapy (sequential and/or concurrent), the specific chemotherapeutic
      drugs, and the dose and intensity of the radiation therapy. Concurrent
      chemoradiotherapy demonstrates a survival advantage compared to sequential
      chemoradiotherapy. Initial data suggest that induction chemotherapy prior to
      concurrent chemoradiotherapy does not further improve survival. The potent
      radiosensitizer gemcitabine has been evaluated in combination chemotherapy with
      radiation therapy and appears to be a promising agent, although further trials
      are needed to define its optimal dose, toxicity and efficacy.

PMID- 16291424
TI  - Using translational research to tailor the use of chemotherapy in the treatment
      of NSCLC.
AB  - The treatment of advanced non-small-cell lung cancer (NSCLC) has improved over
      the past two decades with the availability of new agents such as gemcitabine, the
      taxanes and vinorelbine. Despite these advances, survival prospects remain
      disappointingly low for most patients. Further improvements in response rate and
      survival requires the development of new agents with novel mechanisms of action,
      such as molecularly targeted therapies, which are currently being tested in
      clinical trials. The conventional treatment approach to NSCLC is beginning to
      shift towards the application of specific strategies and techniques, such as
      pharmacogenomics, to tailor treatment to individual patients. Many efforts are in
      progress to identify the clinical predictors of outcome. The discovery of
      prognostic molecular markers, such as the putative suppressor gene (RRM1),
      represents a novel and potential parameter to help guide clinical treatment
      decisions.

PMID- 16291425
TI  - Advances in the treatment of second-line non-small-cell lung cancer.
AB  - Treatment with third-generation chemotherapy agents improves survival and quality
      of life of patients with non-small-cell lung cancer (NSCLC). Despite these
      favorable outcomes, most patients receiving front-line therapy experience disease
      progression. The availability of many new novel agents with activity in NSCLC has
      prompted investigators to explore second-line chemotherapy options. For many
      years, docetaxel was the only approved agent for the second-line treatment of
      NSCLC. More recently, the multi-targeted antifolate pemetrexed has demonstrated
      activity in patients previously treated with chemotherapy with locally advanced
      or metastatic NSCLC. The findings of a phase III trial comparing pemetrexed to
      docetaxel led to the regulatory approval of pemetrexed as monotherapy for the
      second-line treatment of NSCLC. Several other novel therapies, including
      molecular targeting agents such as erlotinib, are under development in clinical
      trials in patients with NSCLC. One of these trials has subsequently led to the
      approval of erlotinib as second- or third-line therapy in advanced NSCLC.

PMID- 16291426
TI  - Pemetrexed: a new cytotoxic agent in the development for first-line non-small
      cell lung cancer.
AB  - Pemetrexed is a new cytotoxic agent that is a standard of care for the second
      line treatment of non-small-cell lung cancer (NSCLC) and treatment of malignant
      pleural mesothelioma. It is currently in clinical development for the first-line
      treatment of NSCLC. In untreated advanced NSCLC, single-agent activity has been
      demonstrated in phase II trials. Pemetrexed has encouraging response rates and a
      favorable toxicity profile. Pemetrexed also has promising activity and acceptable
      toxicity when combined with platinum compounds or gemcitabine. Dietary
      supplementation with low-dose folic acid and vitamin B(12) significantly reduces
      the incidence and severity of toxicities without compromising the antitumor
      activity of pemetrexed. With its innovative mode of action, proven efficacy,
      favorable toxicity profile and convenient administration, pemetrexed represents a
      new therapeutic option for the treatment of advanced NSCLC.

PMID- 16291427
TI  - A ten-year review of progress in the treatment of non-small-cell lung cancer with
      gemcitabine.
AB  - During the past two decades, clinical research has focused on developing
      chemotherapeutic regimens that effectively prolong survival and provide
      palliation for patients with non-small-cell lung cancer (NSCLC). In the mid-to
      late-1990s, several new agents emerged from clinical development and demonstrated
      activity against this disease, including the novel antimetabolite gemcitabine.
      Gemcitabine is one of the most active agents for the treatment of NSCLC. When
      combined with a platinum analog, gemcitabine produces the best progression-free
      survival outcome of any platinum-based regimen in first-line advanced NSCLC
      treatment setting. On the basis of its excellent antitumor activity and favorable
      toxicity profile, gemcitabine has been approved for the first-line treatment of
      locally advanced or metastatic NSCLC.

PMID- 16291428
TI  - Seeking improved outcome in the curative treatment of non-small-cell lung cancer.
AB  - Progress is being made in the treatment of patients with early (stage I-III) and
      unresectable locally advanced (stage III) non-small-cell lung cancer (NSCLC). The
      primary modality of treatment is complete surgical resection of the malignant
      growths. However, not all patients are appropriate candidates for surgery, and
      the majority who undergo surgical resection have a poor survival. Recurrence and
      death are most commonly due to systemic failure, indicating micrometastatic
      disease. Treatments targeted at eradicating micrometastatic disease, such as
      adjuvant therapy, induction chemotherapy, concurrent chemoradiotherapy, and
      intensified radiotherapy, are currently being explored as a means to improve
      outcome in the curative treatment of NSCLC.

PMID- 16291429
TI  - Standard therapy for the treatment of malignant pleural mesothelioma.
AB  - Almost all of the established cytotoxic agents have now been examined both as
      single-agents and in combination chemotherapy regimens as treatment approaches
      for malignant pleural mesothelioma (MPM). Until recently, only few agents have
      consistently produced objective response rates greater than 20%, and no agent has
      improved median survival beyond 10 months. The recent development of several new
      cytotoxic agents, such as the novel antimetabolite pemetrexed, has yielded
      encouraging results. In particular, pemetrexed produces response rates of up to
      45%, and increases median survival to over 12 months when used in combination
      with cisplatin. This doublet-based chemotherapy regimen is now the standard
      therapy for the first-line treatment of MPM.

PMID- 16291430
TI  - Seeking new options for the treatment of small-cell lung cancer.
AB  - The current prognosis for patients with extensive stage (ES) small-cell lung
      cancer (SCLC) remains poor, even though considerable improvements have been made
      in treatments for limited stage (LS) SCLC over the past several decades.
      Pemetrexed is an antimetabolite with an innovative mechanism of action. It
      demonstrates activity both as a single-agent and in combination regimens in
      patients with non-small-cell lung cancer (NSCLC) or malignant pleural
      mesothelioma. With an excellent antitumor activity, favorable tolerability
      profile, ease of administration and convenient schedule in NSCLC patients,
      pemetrexed is currently being investigated in a phase II trial for the first-line
      treatment of ES SCLC. Observations from this trial will help to define the future
      role of pemetrexed in SCLC.

PMID- 16291431
TI  - Perspective on the development of new agents in thoracic cancers.
AB  - The development of several targeted agents that play a critical role in the
      growth and survival of carcinomas has paved the way for a new era in the
      treatment of patients with thoracic malignancies. The novel antimetabolite
      pemetrexed has emerged as a key agent in the treatment of advanced malignant
      pleural mesothelioma (MPM). Inhibitors of the epidermal growth factor receptor
      (EGFR) are one of many promising targeted therapies for non-small-cell lung
      cancer (NSCLC). By utilizing agents that specifically target the biochemical and
      molecular changes underlying cancer, it is possible to envision a future in which
      combinations of therapies treat cancer on multiple fronts, significantly
      enhancing tumor responses and improving survival beyond current expectations.

PMID- 16291432
TI  - The development of gemcitabine and carboplatin in the treatment of non-small-cell
      lung cancer.
AB  - Gemcitabine plus carboplatin is a widely used regimen for the treatment of
      advanced non-small-cell lung cancer (NSCLC). This two drug combination is
      effective, with a favorable safety profile, and is well tolerated in the
      outpatient setting. Gemcitabine/carboplatin prolongs survival compared with
      gemcitabine alone, but with greater hematological toxicity. The combination
      regimen appears to be superior to or equally effective as other regimens
      including mitomycin, ifosfamide and cisplatin (MIC), cisplatin/vinblastine,
      gemcitabine/paclitaxel, paclitaxel/carboplatin and gemcitabine/cisplatin.
      Gemcitabine combined with carboplatin is associated with more hematological
      toxicity, but the incidence of non-hematological toxicity is often significantly
      lower. Gemcitabine/carboplatin also improves patient quality of life, supporting
      its use in treating patients with advanced NSCLC in the outpatient setting.

PMID- 16291433
TI  - Incorporating novel agents with gemcitabine-based treatment of NSCLC.
AB  - First-line treatment with a two-drug combination chemotherapy regimen comprising
      of a platinum-based agent with a third-generation agent has been the accepted
      standard of care in most countries for the treatment of advanced non-small-cell
      lung cancer (NSCLC). Previously, the addition of a third agent to standard
      chemotherapy regimens has failed to improve survival in the majority of
      randomized trials that have been conducted. However, recent findings suggest that
      the addition of the novel targeted agent bevacizumab to a standard
      paclitaxel/carboplatin regimen significantly improves survival. The addition of
      novel agents to gemcitabine-based regimens is therefore a logical approach to
      improving the treatment of advanced NSCLC. Several trials of gemcitabine-based
      regimens with bevacizumab are ongoing.

PMID- 16291434
TI  - Is prehospital blood glucose measurement necessary in suspected cerebrovascular
      accident patients?
AB  - The present study was completed to establish an epidemiologic database defining
      prehospital management of suspected cerebrovascular accidents (CVAs) with
      attention to blood glucose measurement, in the hope of developing recommendations
      for further treatment protocols. On review of 9495 paramedic run reports for the
      24-month period from January 2001 through December 2002, from a low-volume urban
      emergency medical services system, 185 persons presented with CVA signs and/or
      symptoms. Data collected included patient chief complaint, neurologic
      examination, patient age, vital signs, ambulance field times, patient past
      medical history, and blood glucose measurement with resulting prehospital
      interventions, efficacy of interventions, and iatrogenic complications. Five
      persons (2.70%), all medication-controlled diabetics, were found to be
      hypoglycemic. After administration of intravenous dextrose 50% by rescue
      personnel, improvement in neurologic condition was noted in 100% of these cases.
      No sequelae as a result of such care occurred. No inappropriate use, point
      estimate ([0]/[5][0.00%-52.20%]), or unmet need, point estimate ([0]/[9495][0.00%
      0.04%]), of care was noted. The data presented in this study suggest that given
      similar emergency medical service system characteristics, hypoglycemic patients
      presenting with neurologic deficits suggestive of CVAs constitute a rare event,
      associated with medical histories predictive of problems involving glucose
      homeostasis. Blood glucose measurement in persons presenting with CVA signs
      and/or symptoms is only necessary given the presence of history suspicious for
      hypoglycemia, or rescuer inability to obtain adequate patient information.
      Routine prehospital blood glucose measurement in patients with suspected CVA
      appears unnecessary.

PMID- 16291435
TI  - The minimum clinically significant difference in patient-assigned numeric scores
      for pain.
AB  - OBJECTIVE: To determine the minimum clinically significant difference (MCSD) in
      patient-assigned, 11-point numeric rating scale (NRS-11) scores for pain and to
      determine if the MCSD varied with demographic characteristics. METHODS: Eligible
      emergency department patients presenting with pain were asked to rate their pain
      on the NRS-11 every 20 minutes. Subjects compared pain intensity by choosing from
      the following verbal descriptor responses: "a lot more," "a little more," "about
      the same," "a little less," or "a lot less" pain. The MCSD was defined as the
      difference between scores rated "a little more" or "a little less" severe.
      RESULTS: Three hundred fifty-four subjects were enrolled. The MCSD was 1.39 +/-
      1.05 (95% confidence interval, 1.27-1.51). No statistically significant
      difference based on sex or pain etiology was noted. CONCLUSIONS: Findings suggest
      that a change of 1.39 +/- 1.05 (95% confidence interval, 1.27-1.51) on the NRS-11
      is clinically significant when measuring pain.

PMID- 16291436
TI  - Fluid resuscitation of trauma patients: how fast is the optimal rate?
AB  - The Advanced Trauma Life Support guidelines recommend an initial rapid infusion
      of fluid (1-2 L) in trauma and hemorrhage victims as a diagnostic procedure to
      aid treatment decisions. Although patient response to initial fluid resuscitation
      is the key to determining therapeutic strategies, the appropriate rate of
      infusion is not clearly defined. Ninety-nine adult (age >16 years) blunt trauma
      victims with hypotension were enrolled. Patients were classified into 3 groups
      according to hemodynamic state after initial fluid resuscitation and requirement
      of surgical intervention. Total volume and rate of infusion differed
      significantly between the groups (P < .05). Patients requiring fluid
      administration at higher rate were all hemodynamically unstable and required
      immediate surgical intervention. Moreover, rate of infusion was the best
      predictor of the patients who required immediate surgical intervention. Moderate
      fluid infusion rate should be considered to allow identification of the patient's
      response to initial fluid resuscitation.

PMID- 16291437
TI  - Trends in the incidence of carbon monoxide poisoning in the United States.
AB  - PURPOSE: Recent data demonstrate that the mortality rate from carbon monoxide
      poisoning has declined over the past 2 decades. It is not known whether this
      decrease in mortality is reflective of the total burden of carbon monoxide
      poisoning. This study sought to examine trends in other potential indicators of
      the incidence of carbon monoxide poisoning in the United States. BASIC
      PROCEDURES: Published data from US poison control centers (PCCs) were used to
      calculate annual rates of calls regarding carbon monoxide exposures. Data on
      numbers of carbon monoxide-poisoned patients treated with hyperbaric oxygen (HBO)
      were used to calculate annual treatment rates. Trends in rates of carbon monoxide
      related mortality, calls to PCCs, and HBO treatment were then compared. MAIN
      FINDINGS: Contrary to the decline in carbon monoxide-related mortality from 1968
      to 1998, rates of calls to PCCs significantly increased over the same period.
      Neither rates of PCC calls nor HBO treatment changed significantly from 1992 to
      2002. The latter 2 measures were strongly correlated. PRINCIPAL CONCLUSIONS:
      Although deaths from carbon monoxide poisoning have clearly decreased in the
      United States, other indicators of the incidence of the condition suggest that
      the total burden (fatal and nonfatal) may not have significantly changed. Efforts
      to prevent carbon monoxide poisoning should not be relaxed.

PMID- 16291438
TI  - Comparison of racemic albuterol and levalbuterol in the treatment of acute asthma
      in the ED.
AB  - BACKGROUND: Acute asthma is often treated with racemic albuterol, a 1:1 mixture
      of (R)-albuterol and (S)-albuterol. Levalbuterol is the single-isomer agent
      comprised (R)-albuterol, an active bronchodilator, without any effects of (S)
      albuterol. OBJECTIVE: To compare emergency department (ED) admission rates of
      patients presenting with acute asthma who were treated with either racemic
      albuterol or levalbuterol. SETTING: Suburban community teaching hospital. DESIGN:
      Retrospective observational case review. METHODS: Emergency department patients
      presenting with acute asthma at 2 different sites were reviewed over 9- and 3
      month consecutive periods. Outcome measures included ED hospital admission rate,
      length of stay, arrival acuity, and treatment costs. Patients were excluded if
      younger than 1 year or if no treatment of acute asthma was rendered. RESULTS: Of
      the initial 736 consecutive cases, significantly fewer admissions (4.7% vs 15.1%,
      respectively; P = .0016) were observed in the levalbuterol vs racemic albuterol
      group. Of the subsequent 186 consecutive cases, significantly fewer admissions
      were also observed (13.8% vs 28.9%, respectively; P = .021) in the levalbuterol
      vs racemic albuterol group. Treatment costs were lower with levalbuterol mainly
      because of a decrease in hospital admissions. CONCLUSION: Levalbuterol treatment
      in the ED for patients with acute asthma resulted in higher patient discharge
      rates and may be a cost-effective alternative to racemic albuterol.

PMID- 16291440
TI  - Correlation of arterial PCO2 and PETCO2 in prehospital controlled ventilation.
AB  - INTRODUCTION: This study was carried out to estimate the relationship between
      arterial PCO2 (PaCO2) and end-tidal carbon dioxide (PETCO2) during prehospital
      controlled ventilation and also to evaluate variation of the gradient between
      PCO2 and PETCO2 during prehospital transport. METHODS: Measurements of PETCO2
      from capnography values and PaCO2 from arterial blood gases were registered at
      the beginning (T(0)) and at the end (T(end)) of out-of-hospital management. For
      all patients requiring invasive ventilation, the gradient between PCO2 and PETCO2
      was calculated for T(0) and T(end), the PaCO2-PETCO2 variation between T(end) and
      T(0) was also calculated. RESULTS: One hundred patients were included in this
      study (mean age, 58.4 +/- 16.4 years; 57 were male). There was no variation of
      the mean gradient (DeltaPaCO2-PETCO2 ) during transport (8.64 +/- 13.5 mm Hg at
      T(0) and 7.26 +/- 12.94 mm Hg at T(end)). Thirty-six percent of patients (n = 36)
      had a gradient above +10 mm Hg, and for 6% of patients (n = 4) the gradient was
      lower than -10 mm Hg. The PaCO2-PETCO2 gradient was not significantly different
      according to the pathology, but was significantly higher in hypercapnic patients
      compared with hypocapnic or normocapnic patients. In patients with severe head
      injury, the capnia was normalized in 80% of patients at the end of the transport
      according to the last blood gas result. In this subgroup the DeltaPaCO2-PETCO2
      (T(end) - T(0)) gradient was stable between T(0) and T(end) except in 20% of the
      patients for whom the DeltaPaCO2-PETCO2 was lower than -10 mm Hg. Fifty-four
      percent of critical care physicians had modified the respiratory setting after
      the first arterial blood gas results. CONCLUSIONS: The PaCO2 cannot be estimated
      by the PETCO2 in the prehospital setting. There is wide variation in the gradient
      between PCO2 and PETCO2 depending on patient condition, and over time, the
      relationship does not remain constant and thus cannot be useful in prehospital
      ventilation management.

PMID- 16291439
TI  - Defining the outcomes of risk stratification studies of ED patients with chest
      pain: the marginal value of adding revascularization to the composite end point.
AB  - OBJECTIVES: Cardiovascular risk stratification studies use various end points,
      sometimes including revascularization. We assessed whether adding
      revascularization to a strictly defined composite end point of death, acute
      myocardial infarction (AMI), and unstable angina (UA) impacts the likelihood of
      patients attaining the composite end point. METHODS: We conducted a secondary
      analysis of a prospectively collected data set of emergency department patients
      who received an electrocardiogram for chest pain. Patients were followed daily;
      discharged patients had 30-day telephone follow-up. The main outcome was a 30-day
      composite end point of death, AMI, and UA compared with death, AMI, UA, and
      revascularization. RESULTS: There were 4492 patients enrolled (mean age, 52 +/-
      16 years; men, 41%; African American, 68%). One hundred seventy patients were
      revascularized (158 had AMI or UA). Overall, the incidence of death/AMI/UA was
      20.1% (95% confidence interval, 18.9%-21.2%). With revascularization included,
      the incidence of the composite end point was 20.3% (95% confidence interval,
      19.1%-21.5%). CONCLUSION: When both AMI and UA are strictly defined, there
      appears to be a limited role for adding revascularization to a composite end
      point of death, AMI, and UA because most revascularized patients have a diagnosis
      of AMI or UA.

PMID- 16291441
TI  - The prevalence of false-positive cardiac troponin I in ED patients with
      rhabdomyolysis.
AB  - OBJECTIVE: Cardiac troponin I (cTnI) is considered the most specific marker of
      cardiac muscle injury. We encountered several patients with rhabdomyolysis and
      elevated cTnI, although they did not otherwise have evidence of cardiac injury.
      We determined the prevalence of false-positive cTnI in emergency department (ED)
      patients with rhabdomyolysis. METHODS: We conducted a retrospective cohort study
      of ED patients admitted with a diagnosis of rhabdomyolysis. Patients were
      included in the study if they had a serum creatine kinase (CK) of 1000 U/L or
      greater and at least one serum cTnI determination. Patients with positive cTnI
      were considered true positives if they had either electrocardiography (EKG) or
      echocardiography abnormalities; false positives if both the EKG and the
      echocardiography were considered normal; or indeterminate if they did not have
      both an EKG and an echocardiogram. The primary outcome of the study was the
      prevalence of false-positive cTnI. Secondary outcomes included risk
      stratification by cocaine use, myoglobinuria, and renal failure and correlation
      of peak CK and troponin levels. RESULTS: One hundred nine patients were included
      in the final analysis; 55 (50%) patients had a positive cTnI. Of the 55 patients
      with positive cTnI, 32 (58%) were true positives, 18 (33%) were false positives,
      and 5 (9%) were indeterminate. The prevalence of false-positive cTnI was 17%
      (18/109, 95% confidence interval 0.10-0.25). There was no association between
      false-positive cTnI and cocaine use, renal failure, or myoglobinuria. There was
      poor correlation between peak CK and peak cTnI levels (r = -.08, 95% confidence
      interval -0.34 to 0.19). CONCLUSION: The prevalence of false-positive cTnI in ED
      patients with rhabdomyolysis is 17%.

PMID- 16291442
TI  - Sustained oxygenation without ventilation in paralyzed pigs with high-flow
      tracheal oxygen.
AB  - OBJECTIVES: It is generally assumed that ventilation is necessary for
      oxygenation. This study tested if paralyzed animals without respirations can
      maintain arterial oxygenation when administered high-flow oxygen delivered by a
      catheter in the trachea. METHODS:  DESIGN: Prospective observational study.
      SETTING: University research laboratory. PARTICIPANTS: 3 anesthetized/paralyzed
      swine weighing 29.5 +/- 4.2 kg. INTERVENTIONS/OBSERVATIONS: Pigs were intubated,
      anesthetized with intravenous tiletamine and a pentobarbital drip. A femoral
      arterial line was placed to record arterial blood gases and vital signs every 5
      minutes. Respiratory paralysis was obtained with vecuronium 150 microg/kg and
      repeated at any sign of movement. A catheter was placed in the trachea to deliver
      oxygen at 15 L/min. Outflow gas from the endotracheal tube was analyzed for O2
      and CO2. O2 was discontinued at 75 minutes. The institutional animal care and use
      committee approved the protocol. RESULTS: All pigs survived to 75 minutes. PaO2
      was more than 100 mm Hg throughout the study period. Mean PaCO2 was 37.4 +/- 2.8
      mm Hg at baseline, 146 +/- 59 at 30 minutes, then rose above 200 mm Hg in all
      pigs by 45 minutes. Mean arterial pH fell from 7.47 +/- 0.04 at onset to 6.75 +/-
      0.06 at 75 minutes. When oxygen was terminated at 75 minutes, PaO2 fell to 16.5
      +/- 7.6 mm Hg within 5 minutes, and all pigs were sacrificed within 10 minutes.
      For outflow gas, O2 was more than 98% and expired CO2 less than 1% throughout the
      study period. CONCLUSIONS: Paralyzed, unventilated pigs receiving high-flow
      oxygen via a tracheal catheter remained alive after 75 minutes, although a
      profound respiratory acidosis developed.

PMID- 16291443
TI  - The effect of Combitube use on paramedic experience in endotracheal intubation.
AB  - OBJECTIVE: To determine the change in number of endotracheal intubations per
      paramedic after the implementation of Combitube use and to explore consequences.
      METHODS: Before-and-after study; urban/suburban EMS system; population 1 million.
      Number of patients 16 years and older, type of airway used, attempts, and
      successes were abstracted for time periods before and after the use of
      Combitubes. The number of endotracheal intubations/paramedic for each period was
      calculated. RESULTS: Three-year pre-Combitube: patients 50983; 6.6% arrests; 3142
      received an endotracheal intubation attempt with 93.5% success. The average
      annual number of paramedics was 153 with 6.9 +/- 6.4 intubations per paramedic
      per year. Three-year post-Combitube: patients 55959; 6.0% arrests; 2913 received
      an advanced airway attempt: 860 Combitubes, success 89.4%; 2144 endotracheal
      intubations, success 91.6% (95% confidence interval success rate difference, 0.5
      3.3; P = .007). The average annual number of paramedics was 177 with 3.7 +/- 3.3
      intubations per paramedic per year. CONCLUSION: After implementation of the
      Combitube, the number of endotracheal intubation attempts/paramedic and success
      rates decreased.

PMID- 16291445
TI  - Wide-complex tachycardia: beyond the traditional differential diagnosis of
      ventricular tachycardia vs supraventricular tachycardia with aberrant conduction.
AB  - Wide-complex tachycardia (WCT) is defined as a rhythm disturbance with a rate
      greater than 100 beats/min and a QRS complex duration of 0.12 seconds or more in
      the adult patient; in the pediatric patient, both rate and QRS complex width are
      age related. In evaluating this type of tachycardia, there are 2 broad categories
      usually discussed in the medical literature: ventricular and supraventricular
      with aberrant intraventricular conduction. There are several other important
      causes of a WCT encountered in clinical practice, which are less often discussed;
      these tachycardias often require specific therapies differing from the standard
      approach to WCT. These tachycardias are diverse; as such, the pathophysiology
      behind each form of WCT includes toxic, metabolic, and conduction system
      dysfunction mechanisms.

PMID- 16291444
TI  - Correction of factitious hyperkalemia in hemolyzed specimens.
AB  - BACKGROUND: Hemolysis in pediatric specimens is common due to difficult blood
      draws and small-bore intravenous catheters. Values of serum K+ become falsely
      elevated secondary to release of intracellular contents. If a reliable correction
      factor existed for this factitious elevation, repeat K+ measurements might be
      avoided. OBJECTIVE: The aim of the study was to establish a correction factor for
      factitiously elevated K+, using free plasma hemoglobin (p-Hgb) as a measure of in
      vitro hemolysis. METHODS: Twenty whole-blood specimens drawn from healthy adults
      via a 23-gauge needle were divided into 4 aliquots: (1) no manipulation, (2)
      mechanical hemolysis via a 27-gauge needle, (3) addition of potassium acetate
      (KAc), and (4) addition of KAc and mechanical hemolysis. KAc was added to mimic
      potentially significant hyperkalemia. All specimens had standard K+ and p-Hgb
      measurements performed. RESULTS: Nonhemolyzed and hemolyzed K+ ranged from 3.2 to
      8.1 mEq/L and 3.5 to 10.0 mEq/L, respectively. A linear relationship existed
      between the change in K+ and p-Hgb from the nonhemolyzed to hemolyzed specimens.
      A correction factor for K+ of 0.00319 (95% confidence interval, 0.00290-0.00349)
      x p-Hgb was obtained. CONCLUSIONS: A reliable correction factor for factitious
      hyperkalemia in a clinically relevant range exists. By example, using the above
      correction factor, one can predict that the delta K+ in a specimen with 500 mg/dL
      of p-Hgb will be 1.6 mEq/L (range, 1.5-1.7). We suggest that when the lower bound
      of the predicted delta K+ results in a corrected value within the reference
      range, a second blood draw is unnecessary.

PMID- 16291446
TI  - Emergency physicians and the care of children.
AB  - The care of children is an integral aspect of emergency medicine. This article
      reviews the many important contributions that emergency physicians have made in
      advancing the acute care of children.

PMID- 16291447
TI  - Globalization, digitization, and emergency medicine.

PMID- 16291448
TI  - We have a shortage of specialists.

PMID- 16291449
TI  - Computed tomography scan for the diagnosis of esophageal foreign body.

PMID- 16291450
TI  - Emergent hemodialysis for acyclovir toxicity.

PMID- 16291452
TI  - Diagnostic pitfall: carbon monoxide poisoning mimicking hyperventilation
      syndrome.

PMID- 16291451
TI  - Transorbital penetration of the skull base with an occult foreign body.

PMID- 16291453
TI  - Posttraumatic cervical disc herniation: an unusual cause of near drowning.

PMID- 16291454
TI  - Duret hemorrhage is not always suggestive of poor prognosis: a case of acute
      severe hyponatremia.

PMID- 16291455
TI  - Lateral abdominal wall hematoma due to tear of internal abdominal oblique muscle
      in a patient under warfarin therapy.

PMID- 16291456
TI  - Prevalence of postdural puncture headache after ED performed lumbar puncture.

PMID- 16291457
TI  - Distinguishing between aortic dissection and dissecting aneurysm--precise use of
      new nomenclature.

PMID- 16291458
TI  - Accuracy of weight estimation by ED personnel.

PMID- 16291459
TI  - ED environmental tobacco smoke counseling.

PMID- 16291461
TI  - Accuracy of laceration length estimation.

PMID- 16291460
TI  - Discordant results in x-ray interpretations between ED physicians and
      radiologists. A prospective investigation of 30000 trauma patients.

PMID- 16291462
TI  - Nasal intubation or rapid sequence intubation.

PMID- 16291463
TI  - Predictors of inner-city recurrent violence-related injuries.

PMID- 16291464
TI  - Clinical significance of patient-reported questionnaire data: another step toward
      consensus.

PMID- 16291465
TI  - A review of blinding in randomized controlled trials found results inconsistent
      and questionable.
AB  - BACKGROUND AND OBJECTIVE: To determine methods to assess the success of blinding
      in randomized controlled trials (RCTs). METHODS: We searched MEDLINE, the
      Cochrane Controlled Trials Register, and the Cochrane Method Register and
      performed a manual search to target studies that attempt to assess blinding and
      describe the methods used in those studies. RESULTS: A total of 90 reports were
      selected. Reports assessed the success of blinding participants (n = 58), care
      providers (n = 36), and outcome assessors (n = 15). Of the 58 reports assessing
      the success of blinding participants, 54 (93%) reported asking participants to
      guess their treatment assignment. There was no consistency in timing of
      assessment (e.g., once at the end of the trial, 57%, or several times during the
      trial, 26%) or modalities of answering (e.g., "do not know" answers, 43%, or
      participants forced to guess, 31%). A statistical analysis was performed in 57%
      of reports. The statistical analysis mainly compared the proportion of correct
      guesses to those produced by chance (32%) or checked for a relation between
      participants' guesses and treatment assignment (23%). CONCLUSIONS: Methods of
      assessing the success of blinding, analysis and reporting the results were
      inconsistent and questionable.

PMID- 16291466
TI  - Case reports and case series from Lancet had significant impact on medical
      literature.
AB  - BACKGROUND AND OBJECTIVES: Case reports and case series are often the first
      evidence of innovative treatment, but clinical trials need to follow to
      substantiate this evidence. The objective of this article was to evaluate case
      reports or case series describing innovative treatment concerning their impact.
      METHODS: Case reports and case series (n < or = 10) from a high-impact journal,
      The Lancet, published from 1 January 1996 to 30 June 1997, were evaluated
      according to predefined criteria. To assess publication impact, Pubmed, Science
      Citation Index, the Register of Current Controlled Clinical Trials, and the
      Cochrance Controlled Clinical Trials Register were searched. RESULTS: Sixty-four
      case reports and 39 case series were identified. They were cited in average 17
      times (median 6,5; range 0-336). Twenty-Four follow-up trials were identified,
      nine in the register of current controlled clinical trials. CONCLUSION: Case
      reports and case series can be well received, and have significant influence on
      subsequent literature and possibly on clinical practice. Many were followed by
      clinical trials. Often, though, they report rare conditions for which trials may
      not be feasible, and more or less explicitly transfer established treatment into
      other conditions. Overall, there is a strong publication bias favoring positive
      results, and opportunity should be created for publication of follow-up reports.

PMID- 16291467
TI  - A checklist to evaluate a report of a nonpharmacological trial (CLEAR NPT) was
      developed using consensus.
AB  - BACKGROUND AND OBJECTIVE: To develop a checklist of items measuring the quality
      of reports of randomized clinical trials (RCTs) assessing nonpharmacological
      treatments (NPTs). STUDY DESIGN AND SETTING: The Delphi consensus method was used
      to select and reduce the number of items in the checklist. A total of 154
      individuals were invited to participate: epidemiologists and statisticians
      involved in the field of methodology of RCTs (n = 55), members of the Cochrane
      Collaboration (n = 41), and clinicians involved in planning NPT clinical trials
      (n = 58). Participants ranked on a 10-point Likert scale whether an item should
      be included in the checklist. RESULTS: Fifty-five experts (36%) participated in
      the survey. They were experienced in systematic reviews (68% were involved in the
      Cochrane Collaboration) and in planning RCTs (76%). Three rounds of the Delphi
      method were conducted to achieve consensus. The final checklist contains 10 items
      and 5 subitems, with items related to the standardization of the intervention,
      care provider influence, and additional measures to minimize the potential bias
      from lack of blinding of participants, care providers, and outcome assessors.
      CONCLUSIONS: This tool can be used to critically appraise the medical literature,
      design NPT studies, and assess the quality of trial reports included in
      systematic reviews.

PMID- 16291469
TI  - A self-assessment tool was reliable in identifying hazards in the homes of
      elders.
AB  - BACKGROUND AND OBJECTIVES: Falls are a leading cause of fatal and nonfatal
      injuries, particularly among the elderly. A reliable instrument for self
      assessment of home falls hazards would facilitate screening for falls risk. This
      study examined the reliability of self-assessment of home falls hazards by
      elderly women. METHODS AND SETTING: Participants were 52 elderly women, aged 67
      to 97. All evaluations were performed in the participants' homes. Home falls
      hazards were evaluated independently by study participants and by trained
      observers. RESULTS: Kappa statistics indicated good to excellent agreement for
      most of the environmental factors. However, observers were significantly more
      likely than the study participants to report certain tripping hazards,
      particularly objects in walkways. CONCLUSION: This home checklist is an important
      step towards a reliable self-report instrument for measuring home falls hazards.
      Self-assessment appears to be a reliable method for assessing many putative
      hazards of falling in the home. However, our findings raise questions regarding
      the reliable assessment of tripping hazards.

PMID- 16291468
TI  - Minimally important differences were estimated for the Functional Assessment of
      Cancer Therapy-Colorectal (FACT-C) instrument using a combination of distribution
      and anchor-based approaches.
AB  - OBJECTIVE: To estimate minimally important differences (MIDs) on the Functional
      Assessment of Cancer Therapy-Colorectal (FACT-C) instrument using anchor- and
      distribution-based methods. STUDY DESIGN AND SETTING: Preliminary MIDs were
      generated for FACT-C scores based on published results for two samples (n = 60
      and n = 63) from the FACT-C validation study. Preliminary MIDs were confirmed
      using data from a Phase II randomized controlled clinical trial (n = 104) and a
      population-based observational study (n = 568). MIDs were estimated for the
      colorectal cancer subscale (CCS); the FACT-C Trial Outcome Index (TOI-C), which
      is the sum of the CCS, physical well-being, and functional well-being subscales;
      and the FACT-C total score. Both cross-sectional and longitudinal analyses were
      used. RESULTS: MIDs were stable across the different patient samples. The
      recommended MIDs ranged from 2 to 3 points for the CCS, 4 to 6 points for the TOI
      C, and 5 to 8 points for the FACT-C total score. CONCLUSIONS: MIDs can enhance
      the interpretability of FACT-C scores, and they can be used to provide a basis
      for sample size estimation and to determine clinical benefit in combination with
      other measures of efficacy. General guidelines for estimating MIDs for other FACT
      instruments are suggested.

PMID- 16291470
TI  - Changes to the subscales of two vision-related quality of life questionnaires are
      proposed.
AB  - BACKGROUND AND OBJECTIVE: Psychometrically sound questionnaires for the
      assessment of vision-related quality of life (QOL) are scarce. Therefore, the
      objective was to further validate two vision-related QOL questionnaires in a
      Dutch population of visually impaired elderly. METHODS: A total of 329 visually
      impaired older persons referred to low vision services completed the low vision
      QOL (LVQOL) and Vision-Related Quality of Life Core Measure (VCM1) questionnaires
      at baseline, after 1-4 weeks (retest), and after 5 months. Confirmatory factor
      analyses were performed on baseline data. The smallest detectable change (SDC)
      was assessed, based on the standard error of measurement (SEM). Change scores
      between the baseline and 5 months follow-up data were related to a general
      transition question to assess the minimal important change (MIC). Furthermore,
      the MIC was related to the SDC, to examine whether the MICs were detectable
      beyond measurement error. RESULTS: The original factor structures could not be
      confirmed. After omitting items and remodeling, adequate fits were obtained. SDCs
      comprised at least one quarter of the scale for all scales and subscales on the
      individual level and exceeded the MICs on every occasion. CONCLUSION: We propose
      MICs of 5-10 points for the scales and subscales of the LVQOL and VCM1. The
      questionnaires are not useful in the follow-up of individual patients.

PMID- 16291471
TI  - Quantification methods were developed for selection bias by predictability of
      allocations with unequal block randomization.
AB  - BACKGROUND AND OBJECTIVE: A selection of patients for a controlled clinical trial
      may be biased because of prior knowledge of the treatment. With randomized blocks
      of known or guessed lengths, some allocations can be predicted with certainty.
      Previously described methods determine the proportion of predictable cases for
      blocks of equal lengths. It may be useful to make a calculation for unequal
      blocks as well to find a method that reduces this predictability. STUDY DESIGN
      AND SETTING: Quantification methods are developed for series of two and three
      unequal blocks, using the probability of identifying a long block when it comes
      before a short one if it starts with a sequence incompatible with the content of
      a short block. Results are compared with the recently described maximal
      allocation procedure. RESULTS: Predictability is not always reduced by unequal
      blocks and is even worse in some cases, compared to equal blocks. Predictability
      is not necessarily decreased with the maximal allocation procedure. CONCLUSIONS:
      Before choosing an allocation method, it is important to quantify the
      predictability of possible options to reduce selection bias. Several practical
      recommendations are formulated for choosing methods, taking this risk of bias
      into account.

PMID- 16291472
TI  - The Automated Classification of Medical Entities (ACME) system objectively
      assessed the appropriateness of underlying cause-of-death certification and
      assignment.
AB  - BACKGROUND AND OBJECTIVES: To assess the feasibility of using the Automated
      Classification of Medical Entities (ACME) system to objectively define the
      appropriateness of tuberculosis (TB) related underlying cause of death (UCD)
      certification and the accuracy of UCD assignment. METHODS: All death certificates
      issued in 2002 in Taiwan in which TB was mentioned were extracted for analysis.
      Certification of the UCD was defined as inappropriate when ACME used Rule 1 or
      Rule 2 in assigning the UCD. The assignment of the UCD was defined as inaccurate
      when the UCD selected by coders was discordant with the UCD selected by ACME.
      RESULTS: Of the 2,129 death certificates mentioned TB, half (1,067 of 2,129) were
      inappropriately certified by physicians and 16.5% (351 of 2129) had an
      inaccurately assigned UCD by coders. The discrepancy rate in UCD assignment
      between coders and ACME increased when the number of diagnoses increased, TB was
      listed in Part II, and the certification of UCD was inappropriate. CONCLUSIONS:
      It is feasible to use the process information in ACME to objectively define the
      appropriateness of UCD certification and the accuracy of UCD assignment.
      Inappropriate certification of the UCD and TB being listed in Part II were the
      two most important factors associated incorrect interpretation of the World
      Health Organization Selection Rules by coders.

PMID- 16291473
TI  - Best reproducibility of the ankle-arm index was calculated using Doppler and
      dividing highest ankle pressure by highest arm pressure.
AB  - BACKGROUND AND OBJECTIVE: To investigate which method of ankle-arm index (AAI)
      measurement in terms of selected arteries and blood pressure devices yields the
      highest reproducibility. STUDY DESIGN AND SETTING: In this cross-sectional study,
      duplicate AAI measurements were obtained at the right and left side in 320
      postmenopausal women. Analyses were done as proposed by Bland and Altman and
      intraclass correlation coefficients were calculated. RESULTS: The mean and
      standard deviation (SD) of the first and second systolic blood pressure (SBP)
      measurement separately did not differ from the mean and SD of the duplicate SBP
      measurements averaged. Coefficients of repeatability and intraclass correlation
      coefficients were comparable when the ankle SBP was measured in the posterior
      tibial artery or dorsalis pedis artery. Coefficients of repeatability as well as
      the intraclass correlation were better when the SBP in the brachial artery was
      measured with Doppler than with Dinamap. CONCLUSIONS: To achieve the best
      reproducibility and smallest systematic difference in the AAI, single SBP
      measurements should be obtained by Doppler in the brachial artery, posterior
      tibial artery and dorsalis pedis artery. The AAI should be calculated for each
      foot separately by dividing the highest ankle SBP by the highest arm SBP.

PMID- 16291474
TI  - Female hip fracture patients had poorer performance-based functioning than
      community-dwelling peers over 2-year follow-up period.
AB  - BACKGROUND AND OBJECTIVES: Compare performance-based functioning over 2 years
      among elderly women hip fracture patients vs. community-dwelling older women.
      METHODS AND SETTING: 268 hip fracture patients from eight hospitals in Baltimore,
      MD, in 1990-1991, and 486 respondents from the Women's Health and Aging Study I
      (WHAS I) were assessed prospectively at 6-month intervals for 2 years. Usual and
      rapid walking speeds, and chair rise time, were calculated and standardized to
      the baseline distribution of the WHAS subsample. RESULTS: At baseline, all
      respondents were aged 65+ years, White, cognitively intact, and could walk across
      a room independently. Hip fracture patients had significantly poorer functioning
      than WHAS respondents at each follow-up interview through 24 months postfracture.
      The difference was greatest at 6 months: mean walking speed for hip fracture
      patients was approximately one standard deviation lower than for WHAS respondents
      for usual pace (adjusted difference = -1.06, 95% confidence interval (CI) = 
      1.22, -0.89) and rapid pace (adjusted difference = -0.95, 95% CI = -1.13, -0.79).
      These differences were most pronounced among respondents who were aged 80+ years
      or had comorbid conditions. CONCLUSION: Elderly women had poorer performance
      based functioning over 2 years following hip fracture than would be expected by
      normal aging in same-aged women.

PMID- 16291475
TI  - Temporal changes in the distribution of population risk factors attenuate the
      reduction in perinatal mortality.
AB  - BACKGROUND AND OBJECTIVE: To examine and quantify the changing contribution of
      some risk factors to the perinatal mortality rate. METHODS: A population-based
      retrospective cohort study in Northern England compared stillbirth, neonatal, and
      perinatal mortality rates by birthweight, maternal age, plurality, and gender
      between 1982-1990 and 1991-2000. RESULTS: Atlhough the perinatal mortality rate
      fell by 20% between 1982-1990 and 1991-2000, the proportion of births in high
      risk groups (low and high birthweight, older mothers, and multiple births)
      increased. Standardizing the rates for 2000 to the risk factor distribution in
      1982 resulted in lower rates. Changes in the birthweight distribution had the
      largest impact, particularly on neonatal mortality. Nearly a quarter of neonatal
      deaths in Northern England in 2000 can be attributed to the shift in the
      birthweight distribution since 1982, especially to the increase in low
      birthweight births. CONCLUSION: Changes in the distribution of birthweight,
      maternal age, and plurality over the study period attenuated the observed
      reduction in perinatal mortality. It is important to consider differences in the
      population prevalence of such risk factors to make valid geographic or temporal
      comparisons. Reasons for the secular shift in birthweight and the implications of
      any contributing change in obstetric practice require further investigation.

PMID- 16291476
TI  - High blood pressure was associated with cognitive function in middle-age in the
      Whitehall II study.
AB  - BACKGROUND AND OBJECTIVES: Research shows elevated levels of blood pressure in
      midlife to be linked to impaired cognitive performance in old age. However, it
      remains unclear if this association extends to younger age groups. The objective
      of this study was to examine the association between hypertension and a range of
      cognitive abilities in middle aged men and women. METHODS: Data are from the
      Whitehall II study. Measures of blood pressure were obtained at baseline (1985
      1988) and two subsequent phases of data collection (1991-1994 and 1997-1999).
      Cognitive function (memory test, AH 4-I, Mill-Hill, phonemic and semantic
      fluency) was assessed (1997-1999) when participants (N = 5,838) were aged 46-68
      years old. RESULTS: Results show a small inverse association between both
      diastolic and systolic blood pressure and cognitive performance, independent of
      age, education, employment grade, smoking status, alcohol consumption, use of
      antihypertensive medication, diagnoses of diabetes, and cardiovascular disease.
      Similar associations were seen with prospective and cross-sectional analyses. The
      effect of hypertension was stronger in women, and stronger for cognitive measures
      assessing executive function. CONCLUSION: Expanding on previous studies on older
      participants, the present study reports a small, but significant association
      between hypertension and poor cognitive performance in middle-aged men and women.

PMID- 16291477
TI  - Self-report by elderly breast cancer patients was an acceptable alternative to
      surveillance, epidemiology, and end results (SEER) abstract data.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to compare breast cancer
      patients' self-report and surveillance, epidemiology, and end results (SEER)
      abstract data regarding type of treatment received (radiation, chemotherapy, and
      hormonal therapies). METHODS AND DESIGN: Patients 65 years of age or older
      diagnosed during 1999-2001 with stage I-II breast cancer and treated with
      conserving surgery were identified from the Iowa SEER registry; 307 (41% of those
      eligible) completed telephone interviews. SEER-registry abstract data also were
      obtained. RESULTS: Agreement between self-reports and SEER data varied by type of
      treatment, with almost perfect agreement for chemotherapy (kappa = 0.93) and
      moderate to substantial agreement for ever use of hormonal therapy (kappa =
      0.61), receipt of radiation therapy (kappa = 0.60), and current use of hormonal
      therapy (kappa = 0.54). If the SEER data are assumed to be the "gold standard,"
      the sensitivity was generally high (>87%) for all types of treatment. Specificity
      varied according to type of treatment: highest for chemotherapy (98.4%) and
      lowest for radiation therapy (49.0%). Predictive values positive and negative
      were above 75% across type of treatment. CONCLUSION: Using self-reported data was
      an acceptable alternative to reviewing medical records for documenting some types
      of breast cancer treatment.

PMID- 16291478
TI  - A regression model with unexplained residuals was preferred in the analysis of
      the fetal origins of adult diseases hypothesis.
AB  - BACKGROUND AND OBJECTIVE: A continued controversy exists whether the assessment
      of the influence of low birth weight on adult blood pressure necessitates
      adjustment for adult weight in the analysis on the fetal origins of adult
      diseases hypothesis. Here we first explain the difficulty in understanding an
      adjusted multivariate regression model, and then propose another way of writing
      the regression model to make the interpretation of the separate influence of
      birth weight and changes in weight later in life more straightforward. STUDY
      DESIGN AND SETTING: We used a multivariate regression model containing birth
      weight (standard deviation score; SDS), and residual adult weight (SDS) to
      explore the effect on blood pressure (or any other outcome) separately. Residual
      adult weight was calculated as the difference between actual adult weight and the
      expected adult weight (SDS) given on a certain birth weight (SDS). RESULTS: The
      coefficients of birth weight and residual adult weight show directly the effect
      on the analyzed outcome variable. CONCLUSIONS: We prefer to use this regression
      model with unexplained residuals when the adjusted variable is in the causal
      pathway in the analyses of data referring to the fetal origins of adult diseases
      hypothesis.

PMID- 16291480
TI  - Abstracts of the 24th International Congress on Chemotherapy. Manila,
      Philippines. June 4-6, 2005.

PMID- 16291479
TI  - Hospital discharge diagnoses of ventricular arrhythmias and cardiac arrest were
      useful for epidemiologic research.
AB  - OBJECTIVE: We investigated the validity of hospital discharge diagnosis regarding
      ventricular arrhythmias and cardiac arrest. METHODS: We identified patients whose
      record in the PHARMO record linkage system database showed a code for ventricular
      or unspecified cardiac arrhythmias according to codes of the International
      Classification of Diseases, 9th revision, clinical modification (ICD-9-CM). The
      validity of ICD codes for ventricular arrhythmias and cardiac arrest (427.1,
      427.4, 427.41, 427.42, 427.5, 427.69) and ICD codes for unspecified cardiac
      arrhythmias (427.2, 427.60, 427.8, 427.89, 427.9) was ascertained through manual
      review of hospital clinical records. The positive predictive value (PPV) was
      calculated, and differences between characteristics of true and false positives
      were evaluated. RESULTS: The PPV of ICD codes for ventricular arrhythmias and
      cardiac arrest was 82% (95% confidence interval CI = 72-92). True positive
      results were associated with male gender (P = .09) and younger age (P = .05). Of
      the unspecified cardiac arrhythmias 10% (95% CI = 2-18) were identified as
      ventricular arrhythmias or cardiac arrest. CONCLUSION: Hospitalizations for
      ventricular cardiac arrhythmias and cardiac arrest (coded according to ICD-9-CM
      as paroxysmal ventricular tachycardia, ventricular fibrillation, ventricular
      flutter, ventricular premature beats, or cardiac arrest) have a high PPV and are
      useful for selecting events in epidemiological studies on drug-induced
      arrhythmias.

PMID- 16291481
TI  - Why medical abortion is important for women.

PMID- 16291482
TI  - Introducing medical abortion within the primary health system: comparison with
      other health interventions and commodities.
AB  - Over the years, a de-medicalisation strategy has been adopted for a range of
      public health interventions and commodities for the reduction of mortality,
      morbidity and population growth, including those for reproductive, neonatal and
      child health, communicable diseases, and trauma and emergency care, as a way of
      enhancing access to essential services. These experiences carry valuable lessons
      for de-medicalising and simplifying the provision of medical abortion. Like the
      combined oral pill and emergency contraception, which have become non
      prescription drugs despite strident opposition, the abortion pill fundamentally
      alters the relationship between women and their health care providers. Measures
      for de-medicalising primary health services include adoption of simpler
      technology and service protocols, authorisation and training of less qualified
      providers, simplification or elimination of facility requirements, establishment
      of robust referral links to hospitals, increasing user control and self
      medication, and simplifying arrangements for financing. By applying these
      measures, medical abortion can be widely provided as a primary health care
      service. To enable this, however, laws and policies must move beyond the surgical
      abortion paradigm, drugs must become reliably available at affordable cost, and
      women must have access to information that de-stigmatises abortion, enhances
      their options and aims to balance the power between them and their health care
      providers.

PMID- 16291483
TI  - Medical abortion: issues of choice and acceptability.
AB  - Although more than one method of abortion has been available for many years, in
      most countries the provider chooses the method and may be skilled in one method
      only. This paper discusses choice and acceptability of medical abortion from the
      perspective of both women and abortion providers and argues that choice of method
      is important for both. Safety, efficacy, number of visits, how the method works,
      how long it takes for the abortion to be complete and cost all affect
      acceptability. Medical abortion is considered more natural because it happens in
      women's own bodies and can take place at home before nine weeks of pregnancy;
      surgical abortion with vacuum aspiration is simple and over quickly. Unless the
      costs of both methods are similar, however, women and providers will tend towards
      whichever is the cheaper option, limiting choice. Medical abortion is effective
      from when a woman misses her period through 24 weeks of pregnancy, and more women
      and providers need to be made aware of this. In legally restricted situations,
      complications tend to be less serious and easier to treat with early medical
      abortion than after unsafe invasive methods. Ideally, both medical and surgical
      methods should be available, but each can be provided without the other.

PMID- 16291484
TI  - Medical abortion: the possibilities for introduction in the public sector in
      South Africa.
AB  - Medical abortion is safe and effective and has been approved for use in early
      termination of pregnancy in South Africa since 2001. The Department of Health is
      currently considering its introduction in the public health sector. The attitudes
      of women seeking abortion and of health care providers towards medical abortion
      have not previously been described. Data were derived from a quantitative survey
      of 673 women attending abortion services in the provinces of Gauteng, Mpumalanga
      and the Western Cape. In-depth interviews in Soweto and Cape Town were conducted
      with 20 public health doctors, nurses, a social worker and facility managers, and
      in Cape Town with four provincial policymakers. Although medical abortion was not
      yet being offered, 21% of women interviewed were early enough in pregnancy (eight
      weeks or less) to be eligible for medical abortion. Access to health facilities,
      including those for abortion, was reasonable for urban women but more limited for
      rural women. Rural women also incurred greater travel costs to reach a facility.
      Most women thought medical abortion would be acceptable and would have been
      willing to try it, had it been available. Policymakers and providers were
      supportive, as they felt medical abortion could relieve the burden on current
      services. How to increase access to abortion services in rural areas needs to be
      addressed.

PMID- 16291485
TI  - Abortion practice in the northeast Caribbean: "Just write down stomach pain".
AB  - Small island exigencies and a legacy of colonial jurisprudence set the stage for
      this three-year study in 2001-2003 of abortion practice on several islands of the
      northeast Caribbean: Anguilla, Antigua, St Kitts, St Martin and Sint Maarten.
      Based on in-depth interviews with 26 physicians, 16 of whom were performing
      abortions, it found that licensed physicians are routinely providing abortions in
      contravention of the law, and that those services, tolerated by governments and
      legitimised by European norms, are clearly the mainstay of abortion care on these
      islands. Medical abortion was being used both under medical supervision and
      through self-medication. Women travelled to find anonymous services, and also to
      access a particular method, provider or facility. Sometimes they settled for a
      less acceptable method if they could not afford a more comfortable one.
      Significantly, legality was not the main determinant of choice. Most abortion
      providers accepted the current situation as satisfactory. However, our findings
      suggest that restrictive laws were hindering access to services and compromising
      quality of care. Whereas doctors may have the liberty and knowledge to practise
      illegal abortions, women have no legal right to these services. Interviews
      suggest that an increasing number of women are self-inducing abortions with
      misoprostol to avoid doctors, high fees and public stigma. The Caribbean
      Initiative on Abortion and Contraception is organising meetings, training
      providers and creating a public forum to advocate decriminalisation of abortion
      and enhance abortion care.

PMID- 16291486
TI  - Medical abortion in rural Tamil Nadu, South India: a quiet transformation.
AB  - The medical abortion drugs mifepristone and misoprostol are now widely available
      in rural Tamil Nadu, India, and the practice of abortion is being transformed.
      This paper reports on current attitudes and practices concerning medical abortion
      among qualified abortion providers in a rural area of Tamil Nadu. Interviews were
      carried out with a purposive sample of 40 doctors, 15 informants at chemist
      shops, 10 village health nurses and 23 women who had recently had an abortion.
      Twelve of the 37 private doctors who were providing abortions, were providing
      medical abortion to 70-80% of their patients and 12 others to a selected
      minority. Eleven had largely rejected it and still used D&C, two had never heard
      of it. A number of doctors were using misoprostol for cervical dilatation prior
      to D&C. Some doctors and women who were concerned about incomplete abortion and
      heavy bleeding did not have a clear idea of what normal bleeding with medical
      abortion was. Incorrect regimens with second trimester medical abortions might
      have been responsible for cases of excessive bleeding. Most chemist shops said
      they were selling the tablets only on prescription, but doctors reported
      widespread over-the-counter sales. Medical abortion appeared to be quite
      acceptable to most women, and women were increasingly requesting it. Mechanisms
      are needed for sharing information about medical abortion among professionals,
      community health workers and rural families. The state government should develop
      a comprehensive plan for incorporating medical abortion into the public health
      system.

PMID- 16291487
TI  - Availability of medical abortion pills and the role of chemists: a study from
      Bihar and Jharkhand, India.
AB  - The clinical safety, efficacy and acceptability of mifepristone and misoprostol
      in the Indian context have been well studied, but little is known about how they
      are being used, who is using them, how women access them or how providers,
      chemists, women and their partners perceive medical abortion. This paper reports
      on part of a study on these issues, a survey of 209 chemists, in the Indian
      states of Bihar and Jharkhand in 2004. It found that only 34% of the interviewed
      chemists stocked mifepristone and misoprostol, sales volumes were low and there
      was more demand for cheaper, often ineffective preparations for abortion. Men
      were more likely to buy abortifacient drugs than women. Chemists knew
      mifepristone and misoprostol were prescription drugs but less about dosage and
      side effects. Most sales appeared to be prescription driven, but some over-the
      counter sales did occur, especially when ability to pay seemed high or the
      chemist knew the customer. Chemists need accurate information on the drugs they
      sell as abortifacients, encouragement to promote pregnancy tests, training in
      encouraging women to see a provider prior to purchase, and visual and written
      material to hand out. Better adherence to existing regulations for all
      prescription drugs is important, but the best course is to increase the
      availability of low-cost, safe abortion services at primary care level.

PMID- 16291488
TI  - Women's perspectives on medical abortion in Mexico, Colombia, Ecuador and Peru: a
      qualitative study.
AB  - In Latin America, where abortion is almost universally legally restricted,
      medical abortion, especially with misoprostol alone, is increasingly being used,
      often with the tablets obtained from a pharmacy. We carried out in-depth
      interviews with 49 women who had had a medical abortion under clinical
      supervision in rural and urban settings in Mexico, Colombia, Ecuador and Peru,
      who were recruited through clinicians providing abortions. The women often chose
      medical abortion to avoid a surgical abortion; they thought medical abortion was
      less painful, easier or simpler, safer or less risky. They commonly described it
      as a natural process of regulating their period. The fact that it was less
      expensive also influenced their decision. Some, who experienced a lot of pain,
      heavy bleeding or a failed procedure requiring surgical back-up, tended to be
      more negative about it. Regardless of legal restrictions, medical abortion was
      being provided safely in these settings and women found the method acceptable.
      Where feasible, it should be made available but cost should not have to be
      women's primary reason for choosing it. Psychosocial support during abortion is
      critical, especially for those who are more vulnerable because they see abortion
      as a sin, who are young or poor, who have limited knowledge about their bodies,
      whose partners are not supportive or who became pregnant through sexual violence.

PMID- 16291489
TI  - Reaching women with instructions on misoprostol use in a Latin American country.
AB  - In Latin America, where restrictive laws limit women's access to safe abortion
      services, misoprostol is being used to induce abortions, often without correct
      information on dosage or regimens. This study in an unnamed Latin American
      country aimed to identify appropriate channels through which instructions on
      misoprostol use could be disseminated to women. In-depth interviews were carried
      out with physicians, pharmacy staff, women who had had safe abortions and women
      from the community, as well as focus group discussions with advocates of safe
      abortion. Participants considered physicians to be the most appropriate source of
      information and for ensuring confidentiality for both women and provider.
      Participants considered midwives, pharmacists and women's groups as appropriate
      referral points, but not providers of information. Legal restrictions and
      professional risk were the primary reasons why pharmacists rejected this role,
      though many are selling misoprostol. There was a general lack of information
      about misoprostol for medical abortion among both health professionals and women.
      Accurate information about misoprostol use for a wide range of gynaecologic and
      obstetric purposes, including induced abortion, could be incorporated into
      training and educational materials for physicians, midwives and other appropriate
      mid-level providers, as well as pharmacists. Without these alternative
      information channels, access to information would be severely restricted,
      especially in rural areas.

PMID- 16291490
TI  - A project to improve the quality of abortion services in Moldova.
AB  - Abortion has been available legally in Moldova since 1955, and since then the
      abortion rate has gradually declined. The quality of abortion care remains low,
      however, and there is a high level of maternal mortality related to unsafe
      abortion. The goals of the 2005-2015 National Reproductive Health Strategy are to
      reduce unwanted pregnancy, reduce abortion-related morbidity and mortality,
      improve access to and quality of abortion care, including the methods of vacuum
      aspiration and medical abortion. This paper presents information on the current
      abortion law, policy and services in Moldova. It describes a project whose aim is
      to improve the quality of abortion services, including the introduction of
      medical abortion through training of service providers and community education.
      Manual vacuum aspiration has also recently been introduced. The drugs for medical
      abortion are officially approved, a clinical study evaluating the efficacy and
      acceptability of medical abortion in a low-resource setting has been completed,
      and training of providers has been carried out. However, institutionalisation of
      medical abortion faces many problems in relation to organisation of service
      delivery, the higher cost of medical than aspiration abortion, and doctors'
      reluctance to use new methods.

PMID- 16291491
TI  - Study supports the introduction of early medical abortion in Turkey.
AB  - In Turkey, there is an unmet need for induced abortion services provided by the
      public health services, especially in rural and semi-urban areas. The objective
      of this clinical study was to show that early medical abortion could be
      introduced safely in Turkey to improve women's access to services. In the study,
      women aged 18-49 up to 56 days of pregnancy were offered a choice between medical
      abortion with 200 mg mifepristone followed by 400 mcg oral misoprostol and MVA
      with local anaesthesia. 209 chose medical and 149 surgical abortion. Data from an
      additional 112 women were collected to obtain a similar number of surgical
      abortion cases. Women's preference for and satisfaction with the chosen method,
      side effects and complications up to the 14-day follow-up visit were recorded.
      75% of women who chose medical abortion opted for home use of misoprostol. Pain
      with medical abortion on average lasted 3.6 +/- 3.0 days and with surgical
      abortion 3.7 +/- 2.9 days. 90% of women who had medical abortion said they would
      prefer it again compared to 70% of those having surgical abortion. There were
      1.4% ongoing pregnancies in the medical abortion group and none in the surgical
      group. Provider training and familiarity with medical abortion are crucial. The
      high incomplete abortion rate indicates that the dose and regimen of misoprostol
      should be reconsidered. The findings support the introduction of early medical
      abortion in Turkey.

PMID- 16291492
TI  - Availability and acceptability of medical abortion in Nepal: health care
      providers' perspectives.
AB  - Abortion was legalised in Nepal in September 2002 and manual vacuum aspiration is
      the main procedure used for safe abortion. Although medical abortion has not yet
      officially been introduced in Nepal, with the highly porous Indo-Nepal border and
      the easy availability of mifepristone and misoprostrol in Indian chemists' shops,
      it is possible the drugs are entering from Indian markets illegally. This study
      aimed to gauge current awareness of the availability of medical abortion drugs in
      Nepal and explore what health professionals and paramedics felt about the use of
      medical abortion to expand access to safe abortion in the country. Data were
      drawn from interviews with private obstetrician-gynaecologists, general
      physicians, paramedics, ayurvedic and homeopathic practitioners and chemists in
      24 urban municipalities and peri-urban areas in Nepal. Various types of
      allopathic and indigenous forms of medicine for menstrual regulation in the
      Nepalese market were widely known whereas knowledge of the availability of
      mifepristone and misoprostrol was low. Almost all respondents had a positive view
      of the potential for providing mifepristone and misoprostol in Nepal and most
      thought that obstetrician-gynaecologists, general physicians and other certified
      abortion care providers should be able to provide the drugs. Many respondents
      were interested in doing so themselves. Registration of mifepristone and
      misoprostrol is the key to introducing medical abortion in Nepal and should
      happen as soon as possible.

PMID- 16291493
TI  - Human rights begin at birth: international law and the claim of fetal rights.
AB  - In the Universal Declaration of Human Rights, the foundation of human rights, the
      text and negotiating history of the "right to life" explicitly premises human
      rights on birth. Likewise, other international and regional human rights
      treaties, as drafted and/or subsequently interpreted, clearly reject claims that
      human rights should attach from conception or any time before birth. They also
      recognise that women's right to life and other human rights are at stake where
      restrictive abortion laws are in place. This paper reviews the International
      Covenant on Civil and Political Rights, the Convention on the Rights of the
      Child, and the Convention on the Elimination of All Forms of Discrimination
      Against Women, the European Convention for the Protection of Human Rights and
      Fundamental Freedoms, the Inter-American Human Rights Agreements and African
      Charter on Human and People's Rights in this regard. No one has the right to
      subordinate another in the way that unwanted pregnancy subordinates a woman by
      requiring her to risk her own health and life to save her own child. Thus, the
      long-standing insistence of women upon voluntary motherhood is a demand for
      minimal control over one's destiny as a human being. From a human rights
      perspective, to depart from voluntary motherhood would impose upon women an
      extreme form of discrimination and forced labour.

PMID- 16291494
TI  - Abortion in the moral world of the Cameroon grassfields.
AB  - Despite high levels of unsafe abortion in Cameroon, remarkably limited attention
      has been paid to the moral dilemma for women who seek abortions. In-depth
      interviews were conducted with 65 Cameroonian Grasslands women within a hospital
      based study, complemented by participant observation, use of hospital records and
      interviews with key informants. The paper demonstrates how a hidden moral code on
      abortion helps women to exercise individual agency despite prevailing moral
      values. At the same time, women's desire to keep abortion secret can impede
      adequate medical treatment, which in turn can increase the risk of complications
      and mortality. Abortion was more often condemned by the women because of the risk
      to their lives and of infertility rather than for religious reasons or because it
      is illegal. However, the economic and social realities of everyday life often
      overrode their fear of complications when they needed to end a pregnancy. The
      paper concludes that women have already broken through Cameroon's stringent
      restrictions on abortion through their practice. There is a large gap between
      what is permitted under the current law, which is colonial in origin, and women's
      need for legal abortion on broad socio-economic grounds. This calls for
      reflection on liberalisation of the present law.

PMID- 16291495
TI  - Termination of pregnancy for fetal abnormality incompatible with life: women's
      experiences in Brazil.
AB  - Fetal abnormality incompatible with life is a fact and the options for dealing
      with it are abortion or birth followed by death. This paper reports a qualitative
      study of the experience of ten women who had a pregnancy termination in a
      university hospital in Brazil for fetal abnormality incompatible with life. The
      women were interviewed approximately 40 days after the procedure. The experience
      was marked by strong emotions for the women, who had a terrible shock on learning
      of the diagnosis, which was given between 13 and 25 weeks into their pregnancies.
      They cried, and experienced fear, despair, anguish, a sense of uselessness and
      refusal to accept the situation. When they took the decision to terminate their
      pregnancies, the women experienced sadness, despair and guilt, and all these
      feelings caused them intense suffering. The killing of the fetus was the most
      difficult part of the termination for them. Nevertheless, afterwards they were
      satisfied with the decision taken and believed that it was the correct one,
      despite the anguish it caused. The inclusion of fetal abnormality incompatible
      with life in the Brazilian law on pregnancy termination would help to reduce
      women's suffering and contribute to the provision of supportive care by the
      health services.

PMID- 16291496
TI  - Menstrual hygiene among adolescent schoolgirls in Mansoura, Egypt.
AB  - Learning about menstrual hygiene is a vital aspect of health education for
      adolescent girls. This study among 664 schoolgirls aged 14-18 in Mansoura, Egypt,
      asked about type of sanitary protection used, frequency of changing pads or
      cloths, means of disposal and bathing during menstruation. Girls were selected by
      cluster sampling technique in public secondary schools in urban and rural areas.
      Data were collected through an anonymous, self-administered, open-ended
      questionnaire during class time. The significant predictors of use of sanitary
      pads were availability of mass media at home, high and middle social class and
      urban residence. Use of sanitary pads may be increasing, but not among girls from
      rural and poor families, and other aspects of personal hygiene were generally
      found to be poor, such as not changing pads regularly or at night, and not
      bathing during menstruation. Lack of privacy was an important problem. Mass media
      were the main source of information about menstrual hygiene, followed by mothers,
      but a large majority of girls said they needed more information. Instruction in
      menstrual hygiene should be linked to an expanded programme of health education
      in schools. A supportive environment for menstrual hygiene has to be provided
      both at home and in school and sanitary pads made more affordable.

PMID- 16291497
TI  - Reproductive health policy in Norway.

PMID- 16291498
TI  - Using human rights principles to promote quality of abortion care in Brazil.

PMID- 16291499
TI  - The right to be accompanied at birth: new laws in Argentina and Uruguay.

PMID- 16291500
TI  - Reproducibility of surface EMG variables in isometric sub-maximal contractions of
      jaw elevator muscles.
AB  - The aims of this study were: (1) to develop and assess reproducibility of a new
      method for measuring masticatory force in the intercuspal position; (2) to test
      the reproducibility of surface EMG signal amplitude and spectral variables in
      constant force contractions of jaw elevator muscles and its dependency on inter
      electrode distance. The study was performed on the masseter and temporalis
      anterior muscles of both sides of nine healthy volunteers. An intraoral
      compressive-force sensor was used to measure maximal voluntary contraction forces
      in the intercuspal position and to provide a visual feedback on sub-maximal
      forces to the subject. Three experimental sessions were performed in three days.
      In each session, three isometric contractions at 80% of the maximal force were
      sustained by the subjects for 30s. The intra-class correlation coefficient (ICC)
      of the maximal force measure was 71.9%. ICC of average rectified value and mean
      power spectral frequency of the EMG signal increased with inter-electrode
      distance, with values larger than 70% with 30 mm inter-electrode distance. It was
      concluded that surface EMG variables measured in isometric contractions of the
      jaw elevator muscles with the proposed force recording system show good
      reproducibility for clinical applications when a 30 mm inter-electrode distance
      is considered.

PMID- 16291501
TI  - Tracing the endocytic pathway of Aspergillus nidulans with FM4-64.
AB  - Simple procedures using FM4-64 to follow membrane internalization and transport
      to the vacuolar system and endomembranes in Aspergillus nidulans are described.
      FM4-64 internalization is energy, temperature and F-actin dependent, strongly
      suggesting that it occurs by endocytosis. The dye sequentially labels: (i)
      cortical punctuate organelles whose motility resembles that of yeast actin
      patches; (ii) approximately 0.7 microm circular, hollow structures representing
      mature endosome/vacuole; and (iii) intermediate and large (2-3 microm in
      diameter) size vacuoles whose lumen is strongly labeled with 5-(and-6)-carboxy
      2',7'-dichlorofluorescein diacetate (CDCFDA). These large vacuoles possibly
      correspond to the final stage of one branch of the endocytic pathway. In
      addition, FM4-64 labels strongly the mitochondrial network and weakly the nuclear
      membrane. A class of cytoplasmic punctuate organelles which become fluorescent
      very shortly after dye loading and that can move in either apical or basal
      direction at an average rate of 2-3 microm s(-1) is also described. This work
      provides a useful framework for the phenotypic characterization of A. nidulans
      mutants affected in endocytosis.

PMID- 16291504
TI  - Medium-chain acyl-CoA dehydrogenase deficiency: genotype-biochemical phenotype
      correlations.
AB  - The fatty acid oxidation disorder most commonly identified by tandem mass
      spectrometry newborn screening is the potentially fatal medium-chain acyl-CoA
      dehydrogenase deficiency (MCAD). In clinically presenting cases, 80% are
      homozygous for the common mutation, c.985A > G and 18% heterozygous. We screened
      592,785 babies and identified 34 with MCAD, 17 homozygous for c.985A > G, 14 with
      one copy, and 3 with no copy. We sequenced the exons of 19 patients, the 17
      carrying one or no copy of c.985A > G, and two with marginal findings, and
      examined correlations between groups of mutations and biochemical markers. We
      found two known or putative pathogenic mutations in 18 of the 19 patients. Two
      mutations appeared more than once: c.199T > C, not recorded in clinically
      presenting cases (n = 4), and c.583G > A (n = 2). Patients homozygous for c.985A
      > G had the highest levels of neonatal octanoylcarnitine, plasma
      octanoylcarnitine when asymptomatic, and urinary acylglycines. Compound
      heterozygotes of c.985A > G and other mutations had intermediate levels, and
      those without c.985A > G, or heterozygous for that and c.199T > C had the lowest
      levels of these analytes. There was overlap in all values. The c.985A > G and
      c.583G > A mutations appear to have functional effects towards the severe end of
      the spectrum, and the c.199T > C mutation a smaller effect, as has been
      previously postulated. If these results are confirmed and extended, this could
      influence the advice given to parents of babies with MCAD detected by newborn
      screening, and make management more specific. In the meantime, all MCAD patients
      identified by newborn screening have, by definition, a functional defect and
      require careful clinical management.

PMID- 16291505
TI  - Perceived parent-child adjustment in the family reunification among a group of
      runaway adolescents in Hong Kong.
AB  - This qualitative research explores, from the perspectives of runaway adolescents,
      what kind of family responses facilitate and attract a runaway adolescent to
      return home and what kind of parental characteristics facilitate the adolescents'
      adjustment to family reunification. The study carried out in-depth interviews
      with 16 adolescent boys between the ages of 13-17 in Hong Kong who, at the time
      of interview, had returned home after a runaway event and had been living
      together with their parents for considerably long and stable periods of time
      (from one to four years). Implications are directed toward counsellors and
      parents who are concerned with intervening with such at-risk adolescents.

PMID- 16291506
TI  - Adolescents' and parents' future beliefs.
AB  - We investigated how adolescents' and parents' future beliefs, i.e. their goals
      and probability estimations (regarding future career, social and family life)
      were (1) structured, (2) interrelated, and (3) whether adolescents' perceived
      family interaction mediated parents' and adolescents' beliefs, among 239 11-16
      year olds and 197 parents. Using structural equation models we found that (a)
      goals were similarly structured, but unrelated, suggesting cultural transmission
      of goals and autonomous goal setting for adolescents, (b) probability estimations
      were differently structured, and related, suggesting different perceptions of
      opportunities, and (c) family interaction mediated the relationship between
      parents' probability estimations and adolescents' future beliefs, reflecting the
      role of the family for adolescents' future co-planning.

PMID- 16291503
TI  - Sildenafil improves hemodynamic parameters in COPD--an investigation of six
      patients.
AB  - Pulmonary hypertension (PH) is an important predictor of mortality in chronic
      obstructive pulmonary disease (COPD). The phosphodiesterase 5 inhibitor
      sildenafil has been demonstrated to reduce pulmonary arterial pressure (PAP) in
      different diseases. We wanted to investigate the effect of sildenafil on
      hemodynamic parameters and the 6-min walk test (6 MWT) in six patients with
      severe COPD and echocardiographically estimated PH. A 6 MWT was performed and
      hemodynamic parameters were measured by right heart catheterization before and 1
      and 12h after injection of 50mg sildenafil intravenously. A 3-months period of
      peroral sildenafil therapy 50mg twice daily followed and finally hemodynamic
      parameters and a 6 MWT were repeated. Intravenously applied sildenafil could be
      demonstrated to reduce PAP and pulmonary vasculature resistance (PVR)
      significantly. And after 3 months of oral sildenafil, the mean PAP has decreased
      from 30.2+/-5.5 mmHg (range: 24-39 mmHg) to 24.6+/-4.2 mmHg (range: 20-30 mmHg)
      (p=0.01). The PVR has decreased from 401+/-108 dyn s cm(-5) (range: 266-558 dyn s
      cm(-5)) to 264+/-52 dyn s cm(-5) (range: 204-333 dyn s cm(-5)) (p<0.05). Physical
      conditions improved: the 6-min walk distance increased from 351+/-49 to 433+/-52
      m. In conclusion, in six patients suffering from severe COPD we could demonstrate
      significantly improved hemodynamic parameters after 50 mg sildenafil intravenous
      application. And after 3 months of oral sildenafil, walking distance in the 6 MWT
      increased significantly as well as hemodynamic parameters in the five patients
      who had accepted a second right heart catheterization.

PMID- 16291507
TI  - Adolescents with a childhood experience of parental divorce: a longitudinal study
      of mental health and adjustment.
AB  - **This is a prospective Norwegian study of a group of adolescents with an
      experience of parental divorce or separation (n=413) and a comparison group
      without this experience (n=1758). Mean age at T1 was 14.4 years and mean age at
      T2 was 18.4 years. Parental divorce was prospectively associated with a relative
      change in anxiety and depression, subjective well-being, self-esteem, and school
      problems. Considering boys separately, parental divorce was prospectively
      associated only with school problems. Among the girls, divorce was prospectively
      associated with all variables. The effect of divorce on relative change was
      partially mediated by paternal absence.

PMID- 16291508
TI  - Adolescent gender differences in mattering and wellness.
AB  - Mattering to others has been associated with psychosocial well-being and overall
      wellness. The relationship of perceived interpersonal and general mattering to
      overall wellness was studied with a sample of 462 high school students (229 males
      and 233 females). The two measures of perceived mattering (the Mattering to
      Others Questionnaire and the General Mattering Scale) were significantly but
      modestly interrelated (r=.29). Both scales were significantly correlated with
      overall scores on the Wellness Evaluation of Life Style-Teenage form. Females
      perceived they matter to their families, and in general, more than do males, and
      mattering significantly predicted wellness for females.

PMID- 16291509
TI  - Gender and ethnic differences in formal and informal help seeking among Israeli
      adolescents.
AB  - This study examines the willingness of Jewish and Arab Israeli adolescents to
      look for help in times of distress and explores the factors that are associated
      with the willingness of these adolescents to look for help from formal vs.
      informal sources. The sample consisted of 6017 randomly selected respondents, 14
      18 years old, attending secondary schools. Multiple regression analyses were used
      in order to explore what predicts formal vs. informal help seeking. Results
      indicate that satisfaction with school, family and friends, and ethnicity are all
      important predictors that are associated with the willingness of Israeli
      adolescents to ask for formal and informal help. The interaction between gender
      and ethnicity was also examined. The findings present the specific differences
      between formal and informal help seeking and are discussed in the Israeli
      context.

PMID- 16291502
TI  - Expressed sequence tag analysis of the soybean rust pathogen Phakopsora
      pachyrhizi.
AB  - Soybean rust is caused by the obligate fungal pathogen Phakopsora pachyrhizi
      Sydow. A unidirectional cDNA library was constructed using mRNA isolated from
      germinating P. pachyrhizi urediniospores to identify genes expressed at this
      physiological stage. Single pass sequence analysis of 908 clones revealed 488
      unique expressed sequence tags (ESTs, unigenes) of which 107 appeared as multiple
      copies. BLASTX analysis identified 189 unigenes with significant similarities
      (Evalue<10(-5)) to sequences deposited in the NCBI non-redundant protein
      database. A search against the NCBI dbEST using the BLASTN algorithm revealed 32
      ESTs with high or moderate similarities to plant and fungal sequences. Using the
      Expressed Gene Anatomy Classification, 31.7% of these ESTs were involved in
      primary metabolism, 14.3% in gene/protein expression, 7.4% in cell structure and
      growth, 6.9% in cell division, 4.8% in cell signaling/cell communication, and
      4.8% in cell/organism defense. Approximately 29.6% of the identities were to
      hypothetical proteins and proteins with unknown function.

PMID- 16291510
TI  - Brief report: classification of adolescent suicide and risk-taking deaths.
AB  - This study examined the suicide and risk-taking deaths of adolescents aged 12-17
      years between January 1996 and December 2000. The methodology consisted of a case
      file review of government records. One hundred and eighty-seven adolescents (133
      males, 54 females) died by suicide and risk-taking and could be classified into
      three distinct groups: deaths resulting from (1) enduring difficulties (124), (2)
      pivotal life events (26), and (3) adolescent experimentation (28). Avenues for
      the prevention of further suicide and risk-taking deaths are discussed.

PMID- 16291511
TI  - Elongation and secretion of tissue inhibitor of metalloproteinases 1 by human
      microvascular endothelial cells cultured in collagen gels is stimulated by
      mitomycin c.
AB  - During angiogenesis, interactions between endothelial cells (ECs) and the
      surrounding extracellular matrix are influenced by matrix metalloproteinases
      (MMPs) and their cognate inhibitors, the TIMPs. The authors discovered that the
      secretion of TIMP-1 by human microvascular ECs (hmECs) cultured within gels of
      native, fibrillar collagen was increased robustly by mitomycin C (MMC), an
      inhibitor of cell proliferation. In contrast, hmECs cultured on plastic coated
      with gelatin or with native fibrillar collagen exhibited nil (on gelatin) or very
      modest (on native collagen) increases in TIMP-1 upon exposure to MMC. Notably,
      none of the cultures altered the secretion of TIMP-2, or MMP-1 and -2, in
      response to MMC. hmECs cultured within collagen gels elongated significantly
      after exposure to MMC, a response the authors concluded was mediated by TIMP-1,
      because elongation could be inhibited completely with a function-blocking
      antibody to TIMP-1. Moreover, substitution of purified human TIMP-1 for MMC
      induced a similar elongation by hmECs. hmECs cultured within collagen gels did
      not proliferate under the conditions used in this study; therefore, inhibited
      proliferation was not a factor in the altered cell shape and TIMP-1 secretion
      elicited by MMC. These results illustrate that antiproliferative compounds should
      be used with caution in studies of MMP regulation by ECs.

PMID- 16291512
TI  - Functional characteristics of coronary vasomotor function following
      intramyocardial gene therapy with naked DNA encoding for vascular endothelial
      growth factor165.
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. VEGF
      gene therapy improves perfusion of ischemic myocardium in experimental models and
      possibly in patients with end-stage coronary artery disease. In addition to its
      proliferative and migratory effect on endothelial cells, it also activates and up
      regulates endothelial nitric oxide synthase (eNOS). Therefore, the authors
      investigated coronary endothelium-dependent vasodilatation in patients before and
      after VEGF gene therapy. The effect of intracoronary acetylcholine infusion on
      coronary diameter was assessed at baseline and after 3 months follow-up in
      patients with end-stage coronary artery disease treated with VEGF gene and in
      controls scheduled for elective percutaneous transluminal coronary angioplasty
      (PTCA) (acetylcholine test at diagnostic angiography and before a subsequently
      scheduled PTCA). Five out of six VEGF patients experienced a reduction in anginal
      complaints. Angiographic evidence for improved collateral filling was evident in
      two out of six patients. The vasoconstrictive response to acetylcholine was
      partly converted into dilatation. In contrast, the acetylcholine response in
      control patients remained vasoconstrictive. In conclusion, VEGF gene therapy has
      an important beneficial effect on the functional characteristics of the
      myocardial vascular network. Therefore, this therapy can potentially play an
      important role in all stages of the atherosclerotic process.

PMID- 16291513
TI  - Colombian study to assess the use of noninvasive determination of the endothelium
      mediated vasodilation (CANDEV) II: does location of the occlusion device affects
      the accuracy of the diagnosis?
AB  - Endothelial dysfunction (ED), which is often evaluated by flow-mediated
      vasodilation (FMV) in the brachial artery, has been postulated as a predictor of
      cardiac events. Although the upper and forearm location of the occlusion device
      have been used for FMV evaluation, currently there is no consensus whether they
      provide the same information. The main goal of this study was to evaluate if both
      techniques have the same accuracy to differentiate subjects with and without
      cardiovascular risk factors (CRFs). A cross-sectional study in 124 subjects was
      performed. The volunteers were divided in two groups: 62 subjects (20 women and
      42 men) with at least one CRF and 62 (20 women and 42 men) healthy subjects
      without CRFs. FMV measurements using the cuff in the upper arm and forearm with
      intervals of 30 min were taken. In all subjects, %FMV with the cuff located in
      the upper arm was 10.13 +/- 4.5 and 9.8 +/- 4.1 with the cuff located below the
      elbow. In healthy subjects without CRFs the %FMV in the upper arm was 12.19 +/-
      4.0 versus 12.31 +/- 3.4 in the upper forearm, in CRF subjects it was 8.08 +/-
      4.0 vs 7.29 +/- 3.2., respectively. FMV was not affected by the location of the
      cuff in maintaining the test ability and accuracy to differentiate subjects with
      and without CRFs.

PMID- 16291514
TI  - Expression of heme oxygenase-1 protects endothelial cells from irradiation
      induced apoptosis.
AB  - A common side effect of therapeutic use of ionizing irradiation is endothelial
      cell damage resulting in a variety of clinical complications. Thus, preservation
      of endothelial function after irradiation could potentially limit toxicity. Using
      the murine endothelioma cell line bEnd2 we show here that induction of heme
      oxygenase-1 (HO-1) by cobalt protoporphyrine IX (CoPP) inhibits irradiation
      induced apoptosis. In contrast, HO-1 induction by tin protoporphyrine IX (SnPP),
      a HO-1 inhibitor, does not affect survival after irradiation. The protective
      effects of CoPP could be partially reversed by blockade of HO-1 function with
      SnPP after induction by CoPP. Vice versa, blockade of HO-1 function by SnPP was
      reversible using CoPP. Treatment with CoPP inhibited cytochrome c release induced
      by irradiation. These results demonstrate that HO-1 induction and activation
      prior to irradiation inhibits endothelial apoptosis and might be used for
      possible cell protection in vivo.

PMID- 16291515
TI  - Oxidant-mediated activation of cytosolic phospholipase a(2) in pulmonary
      endothelium: role of protein kinase C alpha and a pertussis toxin-sensitive
      protein.
AB  - The authors have previously demonstrated that the oxidant t-buOOH stimulates
      phospholipase A(2) (PLA(2)) activity in bovine pulmonary artery endothelial cells
      (S. Chakraborti et al. American Journal of Physiology, 257, L430-L437, 1989).
      Herein, the authors sought to investigate the mechanism by which t-buOOH
      stimulates PLA(2) activity and the role of protein kinase C (PKC) in this
      scenario. Treatment of bovine pulmonary artery endothelial cells with t-buOOH
      stimulated an aprotinin-sensitive protease activity, PKC activity, and PLA(2)
      activity in the cell membrane. Pretreatment with intracellular Ca(2+) chelator
      (BAPTA-AM), PKCalpha inhibitor (Go6976), cPLA(2) inhibitor (AACOCF(3)), and
      pertussis toxin prevented t-buOOH-stimulated PLA(2) activity. Immunoblot studies
      with aprotinin, cPLA(2), PKCalpha, and Gialpha antibodies revealed their presence
      in the endothelial membrane. Immunoblot studies of the cell membrane isolated
      from t-buOOH-stimulated cells with cPLA(2) and PKCalpha antibodies elicited an
      apparent increase in their immunoreactive protein profiles along with an
      additional 47-kDa immunoreactive fragment in the membrane. t-buOOH caused Gialpha
      phosphorylation in the membrane and pretreatment with Go6976 prevented the
      phosphorylation. Overall, these results suggest that t-buOOH stimulates an
      aprotinin-sensitive protease activity that proteolytically activates PKCalpha and
      that subsequently phosphorylates a pertussis toxin-sensitive protein, resulting
      in the stimulation of cPLA(2) activity in the cell membrane.

PMID- 16291516
TI  - Double-stranded RNA induces the synthesis of retinoic acid-inducible gene-I in
      vascular endothelial cells.
AB  - Viral infection induces various responses in vascular endothelial cells.
      Polyinosinic-polycytidylic acid (poly IC) is a synthetic double-stranded RNA
      (dsRNA), and treatment of cells with poly IC mimics the viral infection to the
      cells. Retinoic acid-inducible gene-I (RIG-I) is a protein belonging to the DExH
      box family and designated as a putative RNA helicase. RIG-I is considered to play
      a role in antiviral responses through the regulation of gene expressions. In the
      present study, the authors treated human umbilical vein endothelial cells
      (HUVECs) with poly IC and found that poly IC induced the expression of RIG-I. The
      poly IC-induced RIG-I expression was inhibited by the preincubation of the cells
      with 2-aminopurine, an inhibitor of dsRNA-dependent protein kinase (PKR).
      Immunohistochemical examination revealed high levels of RIG-I immunoreactivity in
      vascular endothelial cells in the thalamus from rats inoculated with hantavirus.
      Induction of RIG-I by poly IC may be involved in the antiviral responses in
      endothelial cells.

PMID- 16291517
TI  - Endothelial biomedicine: its status as an interdisciplinary field, its progress
      as a basic science, and its translational bench-to-bedside gap.
AB  - The endothelium, a layer of endothelial cells lining the luminal surface of all
      blood vessels, functions as a highly metabolically active organ spatially
      distributed throughout the body. Despite enormous advances in our understanding
      of endothelial cell biology, little awareness of this organ reaches clinical
      practice. The present study aims to document the extent and scope of the bench-to
      bedside gap in endothelial biomedicine, and to offer hypotheses to explain the
      gaping chasm. A PubMed search using keywords "endothelial cells" and
      "endothelium" yielded over 90,000 publications, increasing exponentially over the
      past decade. A Scirus search without date restriction returned journal results
      for the endothelium not greatly fewer than for the epithelium. A survey of
      representative vascular biology meetings revealed a high percentage of talks
      related to the endothelium. The number of grants awarded by the National
      Institutes of Health for studies in endothelial cell biology continues to
      steadily increase. At the bedside, however, few clinicians give consideration to
      the health of the endothelium. A survey of the major medical textbooks revealed a
      paucity of index entries for "endothelial cells" or "endothelium." The
      endothelium does not offer itself for inspection, palpation, percussion, and/or
      auscultation. No convenient blood tests measure endothelial function. The authors
      propose to explain the bench-to-bedside gap in endothelial biomedicine as a
      function of (1) historical constraints, (2) the unseen and diffuse nature of the
      cell layer, (3) the complexity of the system, and (4) its adaptability. Until the
      bench-to-bedside gap closes, the enormous potential of the endothelium as a
      diagnostic, preventive, and therapeutic target will remain largely untapped.

PMID- 16291518
TI  - Dynamic conformational heterogeneities of carcinogen-DNA adducts and their
      mutagenic relevance.
AB  - Arylamines and polycyclic aromatic hydrocarbons (PAHs), which are known as
      "bulky" carcinogens, have been studied extensively and upon activation in vivo,
      react with cellular DNA to form DNA-adducts. The available structure data
      accumulated thus far has revealed that conformational heterogeneity is a common
      theme among duplex DNA modified with these carcinogens. Several conformationally
      diverse structures have been elucidated and found to be in equilibrium in certain
      cases. The dynamics of the heterogeneity appear to be modulated by the nature of
      the adduct structure and the base sequences neighboring the lesion site. These
      can be termed as "adduct- and sequence-induced conformational heterogeneities,"
      respectively. Due to the small energy differences, the population levels of these
      conformers could readily be altered within the active sites of repair or
      replicate enzymes. Thus, the complex role of "enzyme-induced conformational
      heterogeneity" must also be taken into consideration for the establishment of a
      functional structure-mutation relationship. Ultimately, a major challenge in
      mutation structural biology is to carry out adduct- and site-specific experiments
      in a conformationally specific manner within biologically relevant environments.
      Results from such experiments should provide an accurate account of how a single
      chemically homogenous adduct gives rise to complex multiple mutations, the
      earliest step in the induction of cancer.

PMID- 16291519
TI  - Effect of diet, life style, and other environmental/chemopreventive factors on
      colorectal cancer development, and assessment of the risks.
AB  - This review presents a comprehensive, evenhanded evaluation of the evidence from
      experimental, in vitro and human studies associating environmental and
      therapeutic factors with risk of colorectal cancer. Life styles correlated with
      the greatest increase in colorectal cancer risk are the ones that typify a diet
      rich in fat and calories, alcohol drinking and tobacco smoking, and low intake of
      vegetable, fruits and fibers, referred to as a "western diet," as well as
      sedentary style (i.e., no- or low-exercise). This kind of life style has also
      been associated with other chronic diseases (other cancers, obesity,
      dyslipedemia, diabetes, hypertension cardiovascular, and hypertension). The
      evidence does not implicated red meat as a risk factor, and fiber has been shown
      to protect against colorectal adenomas and carcinomas. Calcium, vitamin D,
      folate, and some antioxidant vitamins and minerals (gamma-tocopherol and
      selenium) have protective effects, and daily exercise for > or =30 min results in
      a significant decrease in risk. Estrogen use (hormone replacement therapy)
      substantially reduces colorectal cancer risk in postmenopausal women.
      Nonsteroidal anti-inflammatory drugs (e.g., aspirin) in excessive doses is
      protective, especially in high risk populations, but the side effects of its use
      and cost incurred due to its continued intake over long periods must be carefully
      scrutinized before any recommendations are made for the general public.

PMID- 16291521
TI  - Physiologically-based pharmacokinetic and toxicokinetic models in cancer risk
      assessment.
AB  - Physiologically-based pharmacokinetic (PBPK) and toxicokinetic models are
      increasingly being used for the conduct of high dose to low dose and interspecies
      extrapolations required in cancer risk assessment. These models, by simulating
      tissue dose of toxic chemicals, help address the uncertainty associated with the
      default approaches for interspecies and high dose to low dose extrapolations. The
      applicability of PBPK models in cancer risk assessment has been demonstrated with
      a number of chemicals (e.g., acrylonitrile, 2-butoxyethanol, chloroform, 1,4
      dioxane, methyl chloroform, methylene chloride, styrene, trichloroethylene,
      tetrachloroethylene, vinyl chloride, vinyl acetate). Recent advances in PBPK
      modeling facilitate the consideration of population distribution of parameter
      values, age-dependent changes in physiology and metabolism, multi-route exposures
      as well as multichemical interactions for application in cancer risk assessment.
      Whereas the average values for various input parameters have been used to
      evaluate the age-dependency of tissue dose, the Markov Chain Monte Carlo
      technique can be applied to address variability and uncertainty in parameter
      estimates, thus facilitating a more accurate estimation of cancer risk in the
      population. The PBPK models also uniquely facilitate the simulation of tissue
      dose, and thereby cancer risks, associated with multi-route and multichemical
      exposure situations. Overall, the recent advances reviewed in this article point
      to the continued enhancement of the scientific basis and applicability of PBPK
      models in cancer risk assessment.

PMID- 16291522
TI  - Blackfoot disease and arsenic: a never-ending story.
AB  - Blackfoot disease (BFD) is an endemic peripheral vascular disease confined to the
      southwestern coast of Taiwan. This article reviews the epidemiology, clinical
      manifestations and diagnosis, pathology, etiology and pathogenesis of this
      disease. Sporadic cases of BFD occurred as early as in the early 20th century,
      and peak incidence was noted between 1956 and 1960, with prevalence rates ranging
      from 6.51 to 18.85 per 1,000 population in different villages. Typical clinical
      symptoms and signs of progressive arterial occlusion mainly found in the lower
      extremities, but in rare cases, the upper extremities might also be involved.
      Ulceration, gangrene and spontaneous or surgical amputation were typical fate. An
      extensive pathological study concluded that 30% of the BFD patients had
      histologic lesions compatible with thromboangiitis obliterans and 70% showed
      changes of arteriosclerosis obliterans. Epidemiologic studies carried out since
      mid-20th century revealed that BFD was associated with the consumption of
      inorganic arsenic from the artesian wells. Recent studies confirmed the existence
      of preclinical peripheral vascular disease, subclinical arterial insufficiency
      and defects in cutaneous microcirculation in the residents of the endemic
      villages. A more recent study suggested that the methylation capacity of arsenic
      can interact with arsenic exposure in the development of peripheral vascular
      disease among residents of BFD-endemic areas. The incidence of BFD decreased
      dramatically after the implementation of tap water in these villages over the
      past 2-3 decades. The atherogenicity of arsenic could be associated with its
      effects of hypercoagulability, endothelial injury, smooth muscle cell
      proliferation, somatic mutation, oxidative stress, and apoptosis. However, its
      interaction with some trace elements and its association with hypertension and
      diabetes mellitus could also explain part of its higher risk of developing
      atherosclerosis. Although humic substances have also been suggested as a possible
      cause of BFD, epidemiologic studies are required to confirm its etiologic role.

PMID- 16291523
TI  - Molecular epidemiology of lung cancer in female passive smokers.
AB  - To clarify etiology of lung cancer in nonsmoker females, various studies have
      been done. Particularly, host factors and environmental tobacco smoking (ETS) of
      females have been emphasized. However, traditional epidemiological data showed
      controversial results of sex or gender differences in lung cancer susceptibility
      and suggest presence of some confounders. One of them is that most of
      epidemiology studies are based on self-reports for ETS. To prevent misestimate
      effects of ETS via the self-report, exposure monitoring of ETS is required. On
      the other hand, focusing on genetic polymorphisms in metabolic enzymes and DNA
      repair, molecular epidemiological studies have been done in nonsmoker females.
      Therefore, this review considered: 1. gender differences in lung cancer; 2.
      effects of passive smoking on lung cancer; 3. exposure monitoring of ETS
      including genetic risks of lung cancer to clarify etiology of lung cancer in the
      nonsmoker females with molecular epidemiological discussion.

PMID- 16291526
TI  - Human melanocyte biology, toxicology, and pathology.
AB  - The human melanocytes of the skin, hair, eyes, inner ears, and covering of the
      brain provide physiologic functions important in organ development and
      maintenance. Melanocytes develop from embryonic neural crest progenitors and
      share certain traits with other neural crest derivatives found in the adrenal
      medulla and peripheral nervous system. The distinctive metabolic feature of
      melanocytes is the synthesis of melanin pigments from tyrosine and cysteine
      precursors involving over 100 gene products. These complex biochemical mechanisms
      create inherent liabilities for melanocytic cells if intracellular systems
      necessary for compartmentalization, detoxification, or repair are compromised.
      Melanocyte disorders may involve pigmentation, sensory functions, autoimmunity,
      or malignancy. Environmental factors such as ultraviolet radiation and chemical
      exposures, combined with heritable traits, represent the principal hazards
      associated with melanocyte disorders.

PMID- 16291527
TI  - Carcinogenicity of the chlorination disinfection by-product MX.
AB  - 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone, better known by its
      historical name 'mutagen X' or MX, is a chlorination disinfection byproduct that
      forms from the reaction of chlorine and humic acids in raw water. MX has been
      measured in drinking water samples in several countries at levels that ranged
      from non-detectable to 310 ng/L. Although the concentration of MX in drinking
      water is typically 100- to 1000-fold lower than other common chlorinated by
      products of concern (e.g., trihalomethanes), some have hypothesized that MX might
      play a role in the increased cancer risks that have been associated with the
      consumption of chlorinated water. This hypothesis is based on observations that
      MX, in some test systems, is extremely potent relative to trihalomethanes in
      inducing DNA damage and altering pathways involved in cell growth, and that in
      some epidemiological studies increased cancer rates are associated with the
      bacterial mutagenicity of disinfected water of which MX contributes a significant
      portion. MX also appears to be more potent than other chlorination by-products in
      causing cancer in animals. This article reviews the available evidence on the
      carcinogenicity of MX. MX induced cancer at multiple sites in male and female
      rats, acted as a tumor initiator and promoter, enhanced tumor yields in
      genetically modified rodents, induced a myriad of genotoxic effects in numerous
      in vitro and in vivo test systems, and was a potent inhibitor of gap junction
      intercellular communication. Although the precise mechanism of MX-induced DNA
      damage is not known, MX is able to cause DNA damage through an unusual mechanism
      of ionizing DNA bases due to its extremely high reductive potential. MX may also
      cause mutations through DNA adduction. This article develops a mean cancer
      potency estimate for MX of 2.3 (mg/kg-d)(-1) and an upper 95% percentile estimate
      of 4.5 (mg/kg-d)(-1), and examines the potential health risks posed by this
      chlorination contaminant in drinking water. A discussion of additional data that
      would be desirable to better characterize the risks posed by MX and other
      halogenated hydroxyfuranones follows.

PMID- 16291528
TI  - Critical evaluation of the cancer risk of dibromochloropropane (DBCP).
AB  - Dibromochloropropane (1,2-dibromo-3-chloropropane, DBCP), a pesticide used widely
      for over 20 years to control nematodes on crops, turf and in nurseries, was
      banned by the United States Environmental Protection Agency (US EPA) in 1977
      because of evidence of infertility in men and induction of a variety of tumors in
      laboratory animals. Despite the ban on the use of DBCP, this pesticide remains
      persistent in soil and continues to be detected as a groundwater contaminant in
      areas of past high use, in particular California's Central Valley. In this
      review, we present a critical evaluation of the available scientific literature
      on the potential for DBCP to affect cancer risk, including the results of animal
      cancer bioassays, human epidemiological studies and in vitro and in vivo
      genotoxicity studies. In addition, we provide updated information on DBCP
      chemistry and metabolism, production and past use, current regulations, its
      environmental fate, potential for human exposure and current remediation efforts.
      Results from long-term cancer bioassays in rodents show a statistically
      significant increase in the incidence of malignant and benign mammary gland
      tumors in female rats treated orally with DBCP compared to controls and some
      evidence of increased incidence of mammary fibroadenomas in DBCP low-dose treated
      female rats exposed by inhalation. Significantly increased incidence of tumors of
      the forestomach occurred in both sexes of rats and mice treated orally. Rats
      exposed to DBCP by inhalation showed significant increases in tumors of the
      tunica vaginalis in males; tumors of the pharynx and adrenal gland in females;
      and tumors of the tongue, nasal turbinate and nasal cavity in both sexes compared
      to controls. Male and female mice exposed to DBCP by inhalation experienced
      increased tumor incidence in the lungs and nasal cavity compared to controls.
      Significant increases in tumors of the lung and forestomach have also been
      reported in female mice treated by a dermal route. Although high mortality rates
      in both rat and mouse bioassays limited the ability to detect tumors late in
      life, the induction of a variety of tumors by multiple routes of exposure in two
      rodent species provides clear evidence of a DBCP tumorigenic response. In vitro,
      in vivo and human genotoxicity studies indicate that DBCP is capable of acting as
      a mutagen and clastogen. Few studies have been conducted to assess whether DBCP
      workplace or drinking water exposures affect cancer risk in humans. While case
      control, cohort and ecological epidemiology studies have not found significant,
      positive associations between DBCP exposure and cancer in exposed populations,
      these studies have numerous limitations including small numbers of participants,
      a lack of control for confounding factors, lack of exposure information on DBCP
      and other chemicals and short follow-up times. Given the persistent nature of
      DBCP contamination in areas of past use, efforts should be made to continue
      remediation efforts and follow previously exposed populations for development of
      certain human cancers, including breast, ovarian, stomach, respiratory, oral and
      nasal cancers, among others.

PMID- 16291529
TI  - Herbicides and nitrates in groundwater of Maryland and childhood cancers: a
      geographic information systems approach.
AB  - This hypothesis-generating study explores spatial patterns of childhood cancers
      in Maryland and investigates their potential associations with herbicides and
      nitrates in groundwater. The Maryland Cancer Registry (MCR) provided data for
      bone and brain cancers, leukemia, and lymphoma, for ages 0-17, during the years
      1992-1998. Cancer clusters and relative risks generated in the study indicate
      higher relative risk areas and potential clusters in several counties.
      Contingency table analysis indicates a potential association with several
      herbicides and nitrates. Cancer rates for the four types have a crude odds ratio
      (OR) = 1.10 (0.78-1.56) in relationship to atrazine, and an OR = 1.54 (1.14-2.07)
      for metolachlor. Potential association to mixtures of three compounds give an OR
      = 7.56 (4.16-13.73). A potential association is indicated between leukemia and
      nitrates, OR = 1.81 (1.35-2.42), and bone cancer with metolachlor, OR = 2.26
      (0.97-5.24). These results give insight to generate a hypothesis of the potential
      association between exposure to these herbicides and nitrates and specific types
      of childhood cancer.

PMID- 16291530
TI  - Sexually abused children suffering from post-traumatic stress disorder:
      assessment and treatment strategies.
AB  - Child sexual abuse is a highly prevalent problem that frequently occasions the
      onset of post-traumatic stress disorder in the victimized youngster. This
      selective review addresses recent advances in the assessment and treatment of
      sexually abused children with post-traumatic stress disorder. Firstly, we outline
      the diagnostic criteria for post-traumatic stress disorder and significant
      moderating variables in the development of post-traumatic stress disorder.
      Secondly, we address the clinical assessment of post-traumatic stress disorder in
      sexually abused children, recommending a developmentally sensitive, multi
      informant approach. Thirdly, we consider a family-wide cognitive-behavioural
      treatment framework for sexually abused children with post-traumatic stress
      disorder that involves both child and non-offending caregivers. Fourthly, we
      examine the results of recent evaluation studies supportive of cognitive
      behavioural therapy in the treatment of sexually abused children. Lastly, we
      consider conclusions for clinical practice and directions for future research.

PMID- 16291531
TI  - Telephone-administered cognitive behavior therapy for obsessive-compulsive
      disorder.
AB  - Exposure with response prevention and cognitive behavior therapy are widely
      recognized as effective treatments for obsessive-compulsive disorder.
      Unfortunately, many people with obsessive-compulsive disorder--particularly those
      living in rural areas--do not have access to therapists providing these
      treatments. Accordingly, we investigated the efficacy of telephone-administered
      cognitive behavior therapy for obsessive-compulsive disorder. Two open trials are
      reported, for a total of 33 people with obsessive-compulsive disorder (without
      major depression). The first trial consisted of 12 weeks on a waiting list
      followed by 12 weeks of treatment (delayed treatment). The second trial consisted
      of 12 weeks of immediate treatment. Obsessive-compulsive symptoms did not change
      during the waiting period. Symptoms declined from pre- to post-treatment, with
      gains maintained at 12-week follow-up. For the pooled sample our pre-to-post
      treatment effect size was as large or larger than those obtained in other studies
      of reduced contact treatment, and similar to those of face-to-face exposure with
      response prevention. Our proportion of treatment dropouts tended to be lower than
      those of other reduced contact interventions. The results suggest that telephone
      administered cognitive behavior therapy is effective and well-tolerated, at least
      for people with obsessive-compulsive disorder without major depression. It
      remains to be seen whether this treatment is safe and effective when comorbid
      major depression is present.

PMID- 16291532
TI  - Post-traumatic stress disorder symptoms in United Nations peacekeepers: an
      examination of factor structure in peacekeepers with and without chronic pain.
AB  - Recent factor analytic investigations of post-traumatic stress disorder in
      military veterans suggest that symptoms are best described by either a
      hierarchical 2-factor model or a 4-factor inter-correlated model. Other recent
      evidence suggests that post-traumatic stress disorder and chronic pain are
      intricately related; however, the nature of this relationship is not well
      understood. Factor analysis provides one method for clarifying this relationship.
      In study 1, we compared competing models of post-traumatic stress disorder
      symptom structure in a sample of 400 male United Nations peacekeepers using
      confirmatory factor analysis. Results indicated that both the hierarchical 2
      factor and the 4-factor inter-correlated models provided good fit to the data. In
      study 2, the reliability of these models was assessed in 427 male United Nations
      peacekeepers with chronic back pain and 341 without. Group comparisons of the
      confirmatory factor analysis results revealed that the structure of the
      hierarchical 2-factor and 4-factor inter-correlated models both provided good fit
      to the data in both the chronic back pain and the group without. However, the
      structure of the models for the group with chronic back pain group differed in
      significant ways from that of the group without chronic back pain. Post-traumatic
      stress disorder symptoms in military veterans can be adequately conceptualized
      using either a hierarchical 2-factor or 4-factor inter-correlated model. Chronic
      pain has a minimal influence on overall factor structure. The hierarchical 2
      factor model, while parsimonious, does not provide the degree of symptom detail
      provided by the 4-factor inter-correlated model. Implications for
      conceptualization of post-traumatic stress disorder symptoms for patients with
      chronic back pain and significant post-traumatic stress disorder symptomatology
      are discussed.

PMID- 16291533
TI  - Evaluation of a behaviour analysis and treatment of progressive myoclonus
      epilepsy, type Unverricht-Lundborg: a case study.
AB  - This case study evaluates the clinical effectiveness of a psychological treatment
      within a behaviour medicine approach to epilepsy of a subject with progressive
      myoclonic epilepsy. The pattern of seizure behaviour was identified in the
      behaviour analysis. Self-management skills were taught to the client and in vivo
      exposure was subsequently used in a desensitization process. The main findings in
      this study were that the debilitating effects of the myclonic jerks can be
      reduced and functioning level improved when fear of seizures is reduced. These
      results indicate that psychological treatment can increase the level of
      functioning in clients with progressive myoclonic epilepsy.

PMID- 16291536
TI  - Proximal effects of dependency and self-criticism: conceptual and methodological
      challenges for depressive vulnerability research.
AB  - Research and theorizing on vulnerability to depression has expanded considerably
      in the past 40 years. However, there are a number of challenges and opportunities
      that cannot be adequately resolved or fully exploited within models of
      vulnerability that are typically investigated. Continued progress in
      understanding the link between vulnerability factors and mood depends on a fuller
      understanding of depressive vulnerability factors themselves. Understanding the
      proximal effects of vulnerability factors on both mood and behaviour requires
      methods and analytic models capable of examining moment to moment changes as well
      as an understanding of what underlying needs stressful life events and
      difficulties may threaten. Conceptualizing vulnerability factors more broadly in
      terms of ethological models focusing on social rank and attachment offers a
      number of useful avenues along which vulnerability theory may be expanded.

PMID- 16291538
TI  - Efficacy of telephone-administered cognitive behaviour therapy for obsessive
      compulsive spectrum disorders: case studies.
AB  - Cognitive behaviour therapy is effective for obsessive-compulsive disorder and
      for obsessive-compulsive spectrum disorders such as trichotillomania.
      Unfortunately, many people with these disorders, especially those living in rural
      areas, have limited access to treatment. Telephone-administered cognitive
      behaviour therapy may help address this problem. In a recent study of telephone
      treatment for obsessive-compulsive disorder, we found that such treatment was
      often effective (42% in remission at post-treatment, and 47% in remission at 12
      week follow-up). This article presents 2 case reports of the same treatment,
      applied to obsessive-compulsive spectrum disorders (trichotillomania and
      compulsive skin picking). Treatment was associated with symptom reduction for
      both participants, although one subsequently relapsed. Possible reasons for
      relapse are discussed. The findings encourage further studies to identify the
      characteristics of people most likely to benefit from telephone treatment for
      spectrum disorders.

PMID- 16291537
TI  - Refining diathesis-stress models of depression or introducing ptolemaic
      epicycles? Commentary on Santor.
AB  - Work guided by diathesis-stress models of depression has not been as productive
      or clinically relevant as hoped. Santor (this issue) suggests some promising
      refinements of these theories. He proposes more of a contextual focus and
      addresses temporal instability in presumed diatheses. However, if carelessly
      applied, the innovations he proposes risk being so accommodating of diverse
      findings as to be unfalsifiable. Santor also suggests that the selection of
      coping strategies may be the means by which personality mediates between life
      events and subsequent depression; though reasonable, this elaboration too can
      lead to formulations immune to data. Other issues are raised concerning the
      distinction between fluctuations and disturbances in mood, the role of a history
      of depression, and operationalization of life events. One immediate solution to
      some of the problems inherent in this research may be intensive study of more
      select samples.

PMID- 16291539
TI  - Hierarchical model of generalized and specific vulnerabilities in anxiety.
AB  - This study evaluated a theoretical hierarchical relationship among the general
      anxiety vulnerability variable of neuroticism, the specific vulnerability
      variables of anxiety sensitivity and intolerance of uncertainty, and variables
      reflecting specific anxiety foci including panic symptoms, health anxiety,
      obsessive-compulsive symptoms and generalized anxiety/worry. Questionnaires
      assessing these variables were administered to a non-clinical sample of 91 first
      year psychology students (64.8% women). Path analysis results were highly
      consistent with the hypothesized hierarchical model. Neuroticism was found to
      have a significant direct effect on both anxiety sensitivity and intolerance of
      uncertainty. Both neuroticism and anxiety sensitivity had direct significant
      effects on panic symptoms, neuroticism and intolerance of uncertainty both made
      significant direct contributions to the prediction of worry, and neuroticism made
      a significant direct contribution to the prediction of obsessive-compulsive
      symptoms. Contrary to the hypothesized model, anxiety sensitivity but not
      neuroticism uniquely predicted health anxiety. The results of this study provide
      initial empirical evidence for a hierarchical relationship among general and
      specific vulnerabilities, and specific anxiety manifestations.

PMID- 16291541
TI  - Internet and cognitive behaviour therapy: new opportunities for treatment and
      assessment.

PMID- 16291542
TI  - Internet-based questionnaire assessment: appropriate use in clinical contexts.
AB  - Use of internet-mediated questionnaire assessment is growing in behavioural
      telehealth provision. Literature on web-based psychological testing indicates
      that--while tests used online should be validated for online use--such measures
      can be reliable and valid. However, use of normative data (especially data from
      paper-and-pencil samples) presents problems. Studies have shown score
      distributions may differ across testing media, even when comparisons are made
      between equivalent samples. Data from 3 different projects illustrate such
      (substantive) differences, and the errors that would result from using
      established norms to interpret internet-mediated assessments. Given
      representativeness issues with "internet norms", it is recommended that if online
      tests are used for clinical purposes, this should currently be done in a manner
      that does not rely on normative data.

PMID- 16291543
TI  - Interapy: treatment of post-traumatic stress via the internet.
AB  - This paper describes the theoretical background and procedures (including psycho
      education, screening, treatment protocol and outcome measurement) involved in a
      protocol-driven internet treatment of post-traumatic stress and grief in a group
      of people who have suffered from mild to relatively severe trauma. The paper
      examines the results of 3 outcome and process studies, which were carried out
      initially in a student population and subsequently in the general population of
      highly traumatized people. In the latter study, participants in the experimental
      condition (n = 69) improved significantly more than participants in the waiting
      list control condition (n = 32), with respect to trauma-related symptoms and
      general psychopathology. The effect sizes were large. More than 50% of the
      participants treated showed reliable change and clinically significant
      improvement after treatment for avoidance and depression. Treatment proved most
      beneficial for participants who had suffered from intentional trauma and those
      who had not previously discussed the traumatic events with significant others.
      Content analysis of the publications indicates a remarkable increase in cognitive
      coping during treatment. The possibilities for future research into internet
      driven treatment of post-traumatic stress symptomatology are discussed, including
      the proposal to study the effects of sending a final written letter to a
      significant other person.

PMID- 16291544
TI  - Internet-based treatment for panic disorder.
AB  - Increasingly, the internet is being used as a source of mental health information
      as well as structured treatment programs for people with mental health concerns
      or problems. The present review focuses mainly on research conducted at the
      University of Ballarat in Australia, and Uppsala University in Sweden, on
      internet-based treatment for panic disorder, one of the more common and disabling
      anxiety disorders. Our studies suggest that internet-based cognitive behavioural
      therapy is an effective intervention for panic disorder, and that it is more
      effective than some other self-help therapies. We have found that this mode of
      intervention is associated with clinically significant change, improved
      psychological well-being and functioning, and low participant attrition, provided
      that timely, limited therapist assistance is also provided. This review also
      discusses treatment credibility and participant satisfaction, as well as
      assessment and crisis management issues. Although promising as a form of
      intervention, there is a need for more research on the efficacy of internet-based
      treatment for PD and on comparisons with evidence-based face-to-face therapies.

PMID- 16291545
TI  - Prevention of eating disorders and obesity via the internet.
AB  - Internet technology has been expanding rapidly and has had a dramatic impact on
      how people communicate, learn and share information. This article presents
      applications of internet technology to the psychological domain, particularly in
      the prevention and treatment of eating disorders and obesity. Information
      regarding advantages and disadvantages of computerized interventions are
      discussed and several examples of randomized controlled trials with this
      technology are presented. The studies presented are not meant to be comprehensive
      of psychological interventions in general, but are examples of computerized
      applications from the eating disorder and obesity literatures. Ethical
      considerations and areas for future direction are also discussed.

PMID- 16291546
TI  - Randomized controlled trial of internet-based stress management.
AB  - This study investigated the effects of an internet-based self-help stress
      management program with a randomized controlled design. Of 85 participants, 26%
      dropped out, leaving a final sample of 63 participants with 23 in the treatment
      group and 40 in the waiting list control group. Treatment included applied
      relaxation, problem solving, time management and cognitive restructuring. All
      information and treatment interventions were provided via the internet. Results
      were evaluated with the Perceived Stress Scale and the Hospital Anxiety and
      Depression Scale. Improvements were seen in both groups, with greater
      improvements in the self-help treatment group. It is concluded that the internet
      can be used to provide stress management techniques and result in stress relief.
      However, spontaneous improvement, differential dropout rate and compliance need
      to be monitored in future studies.

PMID- 16291547
TI  - Skin conductance response in Swedish United Nations soldiers exposed to fear
      relevant stimuli.
AB  - The aim of this study was to investigate whether there was a difference in skin
      conductance response between 2 groups of military personnel when exposed to
      emotionally neutral and charged stimuli. The 2 groups were a combat experience
      group (n = 10) with prior experience of emotionally charged war situations and a
      comparison group (n = 10) with no such experience. Results showed that the
      comparison group reacted more strongly to exposure to both charged and neutral
      pictures than did the combat experience group, regardless of exposure time. The
      results are discussed in terms of emotional numbing and differences in anxiety
      state between the 2 groups.

PMID- 16291548
TI  - Expectations and attributions in social anxiety disorder: diagnostic distinctions
      and relationship to general anxiety and depression.
AB  - Contemporary cognitive models suggest that social anxiety disorder arises from a
      number of cognitive factors, including tendencies to form pessimistic (rather
      than optimistic) attributions and expectations for socially-related events. These
      models also assume that the strengths of such attributions and expectations are
      more closely linked with social anxiety than with general anxiety or depression.
      To test these assumptions, a battery of self-report measures was completed by
      participants with a primary diagnosis of generalized social anxiety disorder (n =
      75), panic disorder with agoraphobia (n = 44), or post-traumatic stress disorder
      (n = 59). To examine differences on these cognitive variables, group comparisons
      were performed controlling for general anxiety, depression and medication status.
      Social anxiety disorder, compared with panic disorder with agoraphobia and post
      traumatic stress disorder, was characterized by lower expectations for positive
      social events and higher expectations for negative social events. There was no
      difference among the groups on expectations for non-social positive or negative
      events. Stable and global attributions for social negative events were more
      closely associated with social anxiety disorder than with panic disorder with
      agoraphobia and post-traumatic stress disorder. Correlational analyses also
      revealed specific relationships among social-cognitive measures and social
      anxiety, even after controlling for general anxiety and depression. The results
      are consistent with cognitive models of social anxiety disorder.

PMID- 16291549
TI  - Group cognitive behavioural therapy for heterogeneous anxiety disorders.
AB  - Evidence assessing the outcome of cognitive behavioural therapy for anxiety is
      based on protocols specifically tailored for individual disorders. To date, there
      is little research that would assess a mode of delivery that is designed for
      routine service delivery in typical clinical settings, i.e. group cognitive
      behavioural therapy for unselected, mixed groups of anxiety disorders. The
      objective of this pilot study is to use program evaluation methods to assess the
      immediate and enduring improvements following a 12-week Anxiety Management Group.
      Group participants had any of 5 anxiety disorders and described related
      avoidance. The weekly 2-hour group sessions and daily homework tasks were guided
      by a participant handbook. Patients completed questionnaires at baseline and
      group completion (n = 70); a subset also provided 6-month follow-up data. The
      results from post-group scores on 2 self-report measures show immediate
      reductions equivalent to an effect size of eta = 0.73 (p < 0.001). The effect is
      maintained at 6-month follow-up. This program evaluation suggests that group
      cognitive behavioural therapy for heterogeneous anxiety disorders may be
      effective in a routine clinical setting. A more rigorous study of this
      heterogeneous format appears justified.

PMID- 16291550
TI  - Preliminary examination of the relationship between anxiety disorders in adults
      and self-reported history of teasing or bullying experiences.
AB  - This preliminary study examined the relationship between anxiety disorders and
      self-reported history of teasing or bullying experiences, comparing individuals
      with social phobia, obsessive compulsive disorder, and panic disorder with or
      without agoraphobia. Given that aversive conditioning experiences, such as severe
      teasing, have been proposed to play a role in the development of social phobia
      and that the core feature of social phobia is a fear of social situations in
      which a person may be embarrassed or humiliated, we hypothesized that the social
      phobia group would have a higher rate of self-reported teasing history than would
      the obsessive compulsive disorder or panic disorder groups. Consistent with this
      hypothesis, a relationship between reported history of teasing and diagnosis was
      found. A significantly greater percentage of participants in the social phobia
      group (92%) reported a history of severe teasing experiences compared with the
      obsessive compulsive disorder (50%) and panic disorder (35%) groups. History of
      teasing experiences was also significantly related to an earlier age of onset for
      all 3 anxiety disorders, and to a greater number of self-reported additional
      problems in childhood. These findings suggest further directions for research in
      this area and highlight the significant link between perceptions of teasing in
      childhood and social phobia.

PMID- 16291551
TI  - Health anxiety in children: development and psychometric properties of the
      Childhood Illness Attitude Scales.
AB  - The course of severe anxiety surrounding health issues is unknown. The available
      literature suggests that adults who are overly anxious about health issues often
      interpret or misinterpret their bodily signs and symptoms to be indicative of a
      serious illness. The construct of health anxiety has not been examined in
      children and, to date, there has not been an instrument developed for this
      purpose. The Illness Attitude Scales is one of the most commonly used instruments
      for evaluating fears, beliefs, and attitudes that are associated with
      hypochondriasis and abnormal illness behaviour in adults. We sought to adapt the
      Illness Attitude Scales for use with children ages 8-15 years. The adapted
      Illness Attitude Scales was renamed the Childhood Illness Attitude Scales.
      Revisions to the adult version consisted of simplification of language, revision
      of Likert scale (i.e. 5-point to 3-point scale), and the addition of 7 questions
      to evaluate the role parents/guardians play in facilitating medical attention or
      treatment. Correlations between Childhood Illness Attitude Scales total scores
      and other self-report measures were supportive of the construct-related validity
      of the Childhood Illness Attitude Scales and suggested that it is a useful
      measure of health anxiety in school-age children. Practical and theoretical
      implications of the present results are discussed.

PMID- 16291552
TI  - Memory bias for faces that are perceived as hostile by crime victims with acute
      post-traumatic stress disorder.
AB  - The present study tested, and found support for, the hypotheses that crime
      victims with acute post-traumatic stress disorder have: (i) a general memory
      impairment for faces; and (ii) a memory bias for faces that they perceive as
      hostile, even when these faces are not arranged to show any hostile face
      expressions. It is suggested that crime victims with acute post-traumatic stress
      disorder perform worse on recognition memory due to impaired concentration, and
      that they allocate their limited attentional resources to the detection of
      hostility in others in order to avoid being victimized again. This produces a
      memory bias for perceived hostility even in relatively innocuous everyday
      interactions with others, which contributes to maintaining the sense of serious
      current threat that characterizes post-traumatic stress disorder.

PMID- 16291559
TI  - Gene expression patterns in estrogen (nonylphenol) and aryl hydrocarbon receptor
      agonists (PCB-77) interaction using rainbow trout (Oncorhynchus Mykiss) primary
      hepatocyte culture.
AB  - It was previously reported that in vivo exposure of fish to combined aryl
      hydrocarbon receptor agonist (AhR; 3,3',4,4'-tetrachlorobiphenyl, PCB-77) and
      estrogen receptor agonist (ER; nonylphenol, NP) resulted in potentiation and
      inhibition (depending on dose ratio, sequential order of exposure, and seasonal
      changes) of NP-induced responses by PCB-77. The experiments described in this
      report extend this study by testing whether the effects of PCB-77 on NP-induced
      ER signaling are mediated through AhR-induced transcriptional suppression of
      target genes. Trout hepatocytes were isolated by a two-step collagenase perfusion
      method. After 48-h culture, hepatocytes were exposed to 5 or 10 microM
      nonylphenol (NP) singly and in combination with PCB-77 at 0.1, 1, and 10 microM.
      Cells were harvested after 96-h exposure and processed for RNA isolation. Gene
      expression patterns were quantified using real-time polymerase chain reaction
      (PCR) with specific primer sets and by Northern blot. Exposure of cells to NP
      caused significant elevation of ERalpha, ERbeta, Vtg, and Zrp mRNA expressions,
      while combined exposure with PCB-77 concentration inhibited NP-induced ERs and
      their target gene expressions. Exposure of trout hepatocytes to PCB-77 alone
      caused a rapid induction of cytochrome P-450 (CYP) 1A1 mRNA, and combined
      exposure with NP caused significant reduction in PCB-77 induced CYP1A1 gene
      expression. Exposure of cells to PCB-77 concentrations induced significant
      reduction in AhRalpha mRNA (except 1 microM PCB-77, which caused the induction of
      AhRalpha mRNA levels). AhRbeta mRNA levels in the cells were inhibited after 96-h
      exposure to PCB-77, while combined exposure with 5 microM NP restored the PCB-77
      inhibited AhRbeta mRNA levels to baseline. Taken together, the overall results in
      this study show that PCB-77 suppresses the gene expression of the ERs and their
      target genes by transcription mechanism(s). The roles of AhRs in mediating these
      responses seem to involve the ligand-activated AhR transcriptional induction of
      CYP1A1. In addition to their frequently described functions as activators of
      metabolic potentiation and detoxification of various foreign chemicals, data
      presented in the present study point to other endogenous functions of AhRs that
      need to be studied further.

PMID- 16291560
TI  - Molecular mechanisms involved in the toxic effects of polychlorinated biphenyls
      (PCBs) and brominated flame retardants (BFRs).
AB  - Exposure to polychlorinated biphenyls (PCBs) and brominated flame-retardants
      (BFRs) in human, primates, and rodents is accompanied by neurobehavioral changes.
      These involve adverse effects on both memory and learning and motor activity.
      There are also adverse effects observed on the endocrine and immune system. This
      review is restricted to our laboratory's recent findings of effects of these
      compounds on the nervous system and some molecular effects on the immune system.
      In the nervous system, data showed that PCBs and BFRs produce an effect on
      neurotransmitter transport mechanisms, in particular the neurotransmitter
      dopamine. It was demonstrated that this might explain the loss of dopamine in the
      brain seen after exposure to PCB. Further, it may explain the behavior of
      dopamine in preparations in vitro from brain tissue after exposure to PCB.
      Recently it was also reported that PCB and some BFRs induce formation of reactive
      oxygen species (ROS) in neurons. ROS act as messengers in the nervous system and
      may also be involved in cell death. In the case of PCB exposure, a correlation
      between ROS formation and death of neurons was found. In the immune system it was
      shown that PCBs and some of the BFRs induce formation of ROS in neutrophils
      (granulocytes). This takes place primarily through phosphorylation and subsequent
      activation of the NADPH oxidase. This production of ROS may have an adverse
      effect on the immune system.

PMID- 16291561
TI  - Toxicokinetics and effects of PCBs in Arctic fish: a review of studies on Arctic
      charr.
AB  - In a series of environmentally realistic laboratory experiments, toxicokinetics
      and effects of polychlorinated biphenyls (PCBs) were studied in the Arctic charr
      (Salvelinus alpinus). Winter fasting and emaciation, which are common among
      Arctic charr living in high latitudes, resulted in a redistribution of the
      lipophilic PCBs from lipid-storing tissue such as the muscle, to vital organs
      that must be considered sensitive toward PCB (liver and brain). This
      redistribution was accompanied by a significant potentiation of the hepatic
      cytochrome P-450 (CYP) 1A biomarker response, from low activities in October
      (within those measured in uncontaminated charr) to a high, probably maximum,
      induction in May. Performance studies demonstrated a clear effect of
      environmentally realistic PCB levels on endocrine mechanisms, immune function,
      and seawater preadaptation (smoltification) in charr that had been feed deprived
      for several months after contamination with Aroclor 1254, whereas a high PCB dose
      exerted only minor, if any, effects in charr that had been fed after
      contamination. These results demonstrate that emaciation results in decreased
      dose-response relationships in fish, and indicate that arctic animals undergoing
      seasonal cycles of "fattening" and emaciation may be extra sensitive toward
      persistent, lipophilic organochlorines. Pilot studies on Arctic charr from
      Bjornoya Island revealed marked CYP1A biomarker responses and an upregulation of
      genes involved in cellular homeostatic mechanisms in charr from Lake Ellasjoen
      (high PCB levels).

PMID- 16291562
TI  - Endocrine disruption induced by organochlorines (OCs): field studies and
      experimental models.
AB  - Long-range transport of persistent organic compounds by air and ocean currents
      from industrialized areas resulted in high levels of these pollutants in food
      webs in the Svalbard area. With the aim to test if organochlorine (OC) exposure
      in free-living polar bears from Svalbard affected their plasma steroid hormone
      concentrations, it was found that polychlorinated biphenyls (PCBs) were
      associated with increased progesterone levels in females. The sum of pesticides
      (sigma pesticides) and sigma PCBs contributed significantly negative to the
      variation of the plasma testosterone in males, and the overall contribution of
      the OCs to the plasma cortisol variation was negative. A second objective was to
      study the effects of selected OCs (i.e., PCB 153 and PCB 126) on animal health as
      a consequence of effects on endocrine-regulated functions such as reproduction
      and immunity in a goat model focusing on long-term and low-level exposure during
      the periods of fetal development and in the neonatal period. Additionally, acute
      exposure was studied in adult mice. The results indicated that exposure to low
      doses of PCB 153 in utero and in the suckling period influenced reproductive
      functions and both PCB 153 and PCB 126 exerted immunomodulatory effects on the
      offspring, whereas acute exposure of adult mice had minor effects on male
      reproductive function.

PMID- 16291563
TI  - The potential of ecotoxicoproteomics in environmental monitoring: biomarker
      profiling in mussel plasma using ProteinChip array technology.
AB  - New global technologies, allowing simultaneous analysis of thousands of genes,
      proteins, and metabolites (so-called "omics" technologies), are being adopted
      rapidly by industry, academia, and regulatory agencies. This study evaluated the
      potential of proteomics in ecotoxicological research (i.e., ecotoxicoproteomics).
      Filter-feeding mussels (Mytilus edulis) were exposed continuously for 3 wk to
      oil, or oil spiked with alkylphenols and extra polycyclic aromatic hydrocarbons.
      The influence of chronic exposure on mussel plasma protein expression was
      investigated utilizing ProteinChip array technology in combination with surface
      enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF
      MS). Results indicated that exposure to spiked oil had a more significant effect
      on protein expression in mussels than oil alone. In total, 83 mass peaks (intact
      or modified proteins/peptides) were significantly altered by spiked oil, while 49
      were altered by oil. In exposed organisms, the majority of peaks were upregulated
      compared to controls (i.e., 69% in oil and 71% in spiked oil). Some peaks (32 in
      total) were affected by both treatments; however, the degree of response was
      higher in the spiked oil group for 25 of the 32 commonly affected features.
      Additionally, certain peaks revealed exposure- or gender-specific responses.
      Multivariate analysis with regression tree-based methods detected protein
      patterns associated with exposure that correctly classified masked samples with
      90-95% accuracy. Similarly, 92% of females and 85% of males were correctly
      classified (independent of exposure). Results indicate that proteomics have the
      potential to make a valuable contribution to environmental monitoring and risk
      assessment.

PMID- 16291564
TI  - Pinpointing potential causative agents in mixtures of persistent organic
      pollutants in observational field studies: a review of glaucous gull studies.
AB  - Since different organochlorine contaminants (OCs) are often highly correlated in
      biota, a major challenge in observational field studies is to establish whether
      some OCs are potentially important causative agents of adverse effects. A
      possible solution to this problem is to compare the strength of the effects of
      different OCs on a number of outcome parameters, and then examine if some
      compounds are more consistently reliable predictors of adverse effects. In this
      analysis the four most common OCs (hexachlorobenzene [HCB], oxychlordane, p,p'
      dichlorodiphenyldichloroethylene [DDE], and polychlorinated biphenyls [PCBs]) in
      arctic glaucous gulls (Larus hyperboreus) were ranked in relation to 19 different
      outcome parameters, for which at least 1 of the 4 OCs were significantly related.
      PCBs, made up close to 75% of the measured sigmaOCs, DDE 17-18%, and HCB and
      oxychlordane 3-4%, respectively. Despite relatively low levels of oxychlordane
      and HCB, these compounds tended to be more reliable predictors of adverse effects
      and were ranked highest for 11 and 10 of the 19 outcome parameters, respectively.
      PCBs and DDE were only ranked highest for seven of the outcome parameters.
      Oxychlordane, HCB, DDE, and PCB were "not significant" two, six, six, and eight
      times, respectively. Oxychlordane was significantly more likely to be related to
      adverse effects than DDE. Even if effects of OCs may depend on a complex
      interaction between different compounds, this analysis indicates that adverse
      effects are more likely to occur in glaucous gulls with relatively high
      concentrations of oxychlordane and HCB.

PMID- 16291565
TI  - Polycyclic aromatic hydrocarbon (PAH) ecotoxicology in marine ecosystems.
AB  - Low levels of oil and hence polycyclic aromatic hydrocarbons (PAHs) are naturally
      present in the marine environment, although levels have increased significantly
      following human extraction and use of oil and gas. Other major anthropogenic
      sources of PAHs include smelters, the use of fossil fuels in general, and various
      methods of waste disposal, especially incineration. There are two major sources
      for PAHs to marine ecosystems in Norway: the inshore smelter industry, and
      offshore oil and gas production activities. A distinction is generally made
      between petrogenic (oil-derived) and pyrogenic (combustion-derived) PAHs.
      Although petrogenic PAHs appear to be bioavailable to a large extent, pyrogenic
      PAHs are often associated with soot particles and less available for uptake into
      organisms. There is extensive evidence linking sediment-associated PAHs to
      induction of phase-I enzymes, development of DNA adducts, and eventually
      neoplastic lesions in fish. Most studies have focused on high-molecular-weight,
      carcinogenic PAHs such as benzo[a]pyrene. It is less clear how two- and three
      ring PAHs affect fish, and there is even experimental evidence to indicate that
      these chemicals may inhibit some components of the phase I system rather than
      produce induction. There is a need for increased research efforts to clarify
      biological effects of two- and three-ring PAHs, PAH mixtures, and adaptation
      processes in marine ecosystems.

PMID- 16291566
TI  - May organic pollutants affect fish populations in the North Sea?
AB  - The North Sea is a highly productive area with large fish populations that have
      been extensively harvested over the past century. North Sea fisheries remain
      important to the surrounding countries despite declining fish stocks over the
      past decades. The main reason for declining fish stocks is nearly certainly
      overfishing, but other environmental pressures also affect fish populations, such
      as eutrophication, climate change, and exposure to metals and organic pollutants,
      including polyaromatic hydrocarbons (PAHs), alkylphenols, and organochlorine
      compounds. There are three main sources of organic pollutants in the North Sea:
      atmospheric, land-based sources, and inputs from offshore gas and oil
      installations. All three sources contribute to elevated concentrations of organic
      pollutants in the North Sea compared to the Norwegian Sea. There is evidence that
      chlorinated organic contaminants were present in sufficiently high concentrations
      in the southern North Sea two decades ago, to alter embryonal development in
      fish. The results from extensive, long-term monitoring programs show that some
      diseases decreased whereas other increased in the southern North Sea and that,
      among other factors, contaminants may play a role in the temporal changes
      recorded in disease prevalence. Recent studies demonstrated that components in
      offshore effluents may affect fish reproduction and that tissues of fish near oil
      rigs are structurally different to tissues of fish from reference areas. Data on
      effluents from offshore activities have recently become available through an
      international workshop (BECPELAG) and follow-up studies.

PMID- 16291567
TI  - Perinatal exposure to low doses of PCB 153 and PCB 126 affects maternal and
      neonatal immunity in goat kids.
AB  - Pregnant does (10 goats/group) were dosed orally either with polychlorinated
      biphenyl (PCB) 153 (98 microg/kg body weight/d) or PCB 126 (ng/kg body weight/d)
      dissolved in corn oil or with corn oil only (control group) from gestation day
      (GD) 60 until delivery. An additional group (n = 5) of pregnant does received the
      synthetic estrogen diethylstilbestrol (DES; 0.4 microg/kg body weight/d) by
      intramuscular injection using the same treatment schedule as for the PCB groups.
      Blood samples for immune analysis were collected at wk 0, 1, 2, 4, 6, and 8 of
      age. The effects of perinatal PCB exposure on postnatal humoral immune responses
      were examined by assessing the levels of total immunoglobulin G (IgG) and
      immunoglobulins to specific microbes at wk 0, 1, 2, 4, 6, and 8 of age, and
      immune responses following immunization of kids at 2 wk of age. PCB 153 exposure
      suppressed maternal and neonatal immunity, as demonstrated by reduced transfer of
      maternal IgG and specific antibodies to the environmental microbes
      Arcanobacterium pyogenes, Mannheimia haemolytica, and reovirus (REO-1).
      Furthermore, PCB 153 reduced the level of maternal antibodies to Mycobacterium
      avium paratuberculosis and equine influenza virus (EIV-1) in the newborn kids.
      The antibody response against EIV-1 was significantly higher in PCB 153-exposed
      kids 2 wk following immunization. PCB 126 exposure reduced the levels of maternal
      antibodies to REO-1. In contrast, gestational exposure to PCB 126 increased the
      concentrations of maternal antibodies to tetanus toxoid. No differences from
      controls in plasma total IgG levels at birth or colostrum IgG concentrations were
      observed in the PCB 126-treated does. However, a significant reduction in IgG
      levels from GD 60 until delivery was found in this group. Gestational exposure to
      DES reduced the concentrations of maternal antibodies against A. pyogenes, M.
      haemolytica, M. avium Paratuberculosis, and REO-1. These results suggest that
      perinatal exposure to low doses of PCB 126 and PCB 153 affects the maternal
      immunity in kids. The difference in responses between PCB 126 and PCB 153
      treatment groups may strengthen the hypothesis that PCBs mediate immunotoxic
      effects through both AhR-dependent and -independent mechanisms. The observation
      that the effects produced by PCB 153 resembled those produced by DES raises the
      question of whether this congener may modulate immunity by estrogenic mechanisms.

PMID- 16291568
TI  - Chromosome aberrations and DNA strand breaks in glaucous gull (Larus hyperboreus)
      chicks fed environmentally contaminated gull eggs.
AB  - In this present laboratory study, our results suggest that a complex mixture of
      pollutants found in the marine environment exerts genotoxic effects on glaucous
      gull (Larus hyperboreus) chicks fed environmentally contaminated gull eggs.
      Chromosome aberrations, quantified by cytogenetic analysis of blood cells, and
      DNA strand breaks, quantified by agarose gel electrophoresis and image data
      analysis, were determined in glaucous gull chicks fed environmentally
      contaminated gull eggs (exposed group) and in chicks fed hen eggs (control
      group). For both female and male gulls, the fraction of damaged metaphases was
      quantitatively higher in exposed than in control groups. On the other hand, the
      differences between the control and the exposed groups were more relevant when
      the chromosomal aberration data were treated as group totals rather than at the
      individual level. Consistent results were obtained in the DNA strand break
      analyses. The control group appeared to display a greater median molecular length
      (MML) than the exposed group.

PMID- 16291569
TI  - Endocrine disruptors in the marine environment: mechanisms of toxicity and their
      influence on reproductive processes in fish.
AB  - Recent research demonstrated how endocrine-disrupting chemicals (EDCs) may
      disturb wildlife populations and possibly also represent a human health risk.
      Much of the focus has been on (anti-)estrogenic and (anti-)androgenic effects,
      and these effects are thought to be mediated through the estrogen (ER) and
      androgen (AR) receptors, respectively. The seriousness of the problem has led
      international bodies such as the Organization for Economic Cooperation and
      Development (OECD) and the European Union (EU) to initiate large research
      programs and developments toward new guidelines and regulations. EDCs have both
      synthetic and natural sources. The mechanisms of action of EDCs can be divided
      into: (1) agonistic/antagonistic effect ("hormone mimics"), (2) disruption of
      production, transport, metabolism, or secretion of natural hormones, and (3)
      disruption of production and/or function of hormone receptors. However, the
      number of nuclear hormone receptors being potential targets for EDCs has
      increased dramatically the last decade, opening up new avenues for possible
      endocrine disruptor effects. In studies with Atlantic salmon, data showed that 4
      nonylphenol, a model xenoestrogen previously used in large volumes, for example,
      in paints and detergents, acts as an estrogen mimic, as a steroid metabolism
      disruptor, and by modulating estrogen receptor (ER) levels, indicating that one
      single compound exerts all of these three mechanisms, depending on the dose given
      to the organism. A hypothesis explaining this observation is that the nature of
      the effect of an EDC is determined by dose-dependent routing and cross-talk
      between different classes of nuclear receptors.

PMID- 16291570
TI  - Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in the
      Grenlandfjords (Norway)--disposition, levels, and effects.
AB  - Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) are regarded
      as highly toxic. Their lipophilicity and persistence also render them subject to
      bioaccumulation. The Grenlandfjords (southern Norway) have long been polluted by
      PCDD/Fs through the magnesium production at Heroya (1951-2002). Therefore,
      extensive environmental monitoring was performed in the area, and the project
      "Dioxins in the Grenlandfjords--DIG" was launched to study abiotic mass balances,
      biotic processes and ecological risk. This article describes some results from
      DIG on the dispositions of PCDD/Fs in the food web and biological effects.
      Furthermore, data from the Norwegian monitoring of the Grenlandfjords are
      described. Differences in cod liver PCDD/F levels were found between stations,
      with the highest concentrations in the inner fjord (the Frierfjord), closest to
      the pollution source. Furthermore, considerable decreases in the concentrations
      followed the large discharge reductions (1975 and 1990). Contrary to earlier food
      web studies on other organochlorines, it was found that the concentrations of
      PCDD/Fs decline with higher trophic level. Higher chlorinated congeners also
      constituted a lower percentage of sigmaPCDD/Fs higher in the food chain. The
      results indicated a limited bioaccumulation of PCDD/Fs, especially of higher
      chlorinated congeners, likely due to reduced membrane permeability (high
      molecular size), and possibly slow transport through intestinal aqueous phases.
      Hepatic cod 7-ethoxyresorufin O-deethylase (EROD) activities differed between the
      Frierfjord and the Eidangerfjord, showing the different PCDD/F exposure in the
      two fjords. Furthermore, seasonal variations in cytochrome P-450 (CYP) 1A
      activity were shown, with different responses between genders. The differences
      were likely linked to the reproductive cycle of the fish.

PMID- 16291571
TI  - Microsomal triglyceride transfer protein -493T variant reduces IDL plus LDL apoB
      production and the plasma concentration of large LDL particles.
AB  - The microsomal triglyceride transfer protein (MTP) is essential for the synthesis
      and secretion of apolipoprotein B (apoB)-containing lipoproteins. We investigated
      the role the MTP -493G/T gene polymorphism in determining the apoB-100 secretion
      pattern and LDL heterogeneity in healthy human subjects. Groups of carriers of
      the T and the G variants (n = 6 each) were recruited from a cohort of healthy 50
      yr-old men. Kinetic studies were performed by endogenous [(2)H(3)]leucine
      labeling of apoB and subsequent quantification of the stable isotope
      incorporation. apoB production rates, metabolic conversions, and eliminations
      were calculated by multicompartmental modeling (SAAM-II). LDL subfraction
      distribution was analyzed in the entire cohort (n = 377). Carriers of the MTP 
      493T allele had lower plasma LDL apoB and lower concentration of large LDL
      particles [LDL-I: 136 +/- 57 (TT) vs. 175 +/- 55 (GG) mg/l, P < 0.01]. Kinetic
      modeling suggested that MTP -493T homozygotes had a 60% lower direct production
      rate of intermediate-density lipoprotein (IDL) plus LDL compared with homozygotes
      for the G allele (P < 0.05). No differences were seen in production rates of
      large and small VLDL, nor were there any differences in metabolic conversion or
      elimination rates of apoB between the genotype groups. This study shows that a
      polymorphism in the MTP gene affects the spectrum of endogenous apoB-containing
      lipoprotein particles produced in humans. Reduced direct production of LDL plus
      IDL appears to be related to lower plasma concentrations of large LDL particles.

PMID- 16291572
TI  - Activation of the farnesoid X receptor improves lipid metabolism in combined
      hyperlipidemic hamsters.
AB  - The transcription factor farnesoid X receptor (FXR) has recently been implicated
      in the control of hepatic triglyceride production. Activation of FXR may
      ameliorate hypertriglyceridemia, a cardinal feature of the metabolic syndrome.
      Because hamsters share many characteristic features of human lipid metabolism, we
      used a high-fructose-fed hamster model to study the impact of FXR activation with
      chenodeoxycholic acid (CDCA) on plasma lipoprotein metabolism. Male Syrian
      hamsters fed a diet containing 60% kcal from fructose for 2 wk developed
      hypertriglyceridemia and hypercholesterolemia (+120 and +60%, P = 0.005 and
      0.0004 vs. controls) due to increased hepatic lipoprotein production. This could
      be largely attributed to enhanced hepatic de novo lipogenesis, as indicated by
      increased expression of sterol regulatory element-binding protein-1, fatty acid
      synthase, and steaoryl-CoA desaturase-1. Lipoprotein analysis demonstrated that
      the increase in plasma triglycerides occurred in the VLDL density range, whereas
      increases in VLDL, IDL/LDL, and HDL cholesterol accounted for the elevated plasma
      cholesterol concentrations. Addition of 0.1% CDCA to the high-fructose diet
      decreased hepatic de novo lipogenesis and consequently triglyceride production
      and prevented the increases in plasma triglycerides and cholesterol (-40 and 
      18%, P = 0.03 and 0.03 vs. high fructose-fed animals). CDCA-treated animals had
      lower VLDL triglycerides and decreased VLDL and IDL/LDL cholesterol plasma
      concentrations. These data demonstrate that activation of FXR with CDCA
      effectively lowers plasma triglyceride and cholesterol concentrations, mainly by
      decreasing de novo lipogenesis and hepatic secretion of triglyceride-rich
      lipoproteins. Our studies identify activators of FXR as promising new tools in
      the therapy of hypertriglyceridemic states, including the insulin resistance
      syndrome and type 2 diabetes.

PMID- 16291573
TI  - Atrial natriuretic peptide stimulates lipid mobilization during repeated bouts of
      endurance exercise.
AB  - Atrial natriuretic peptide (ANP) controls lipolysis in human adipocytes. Lipid
      mobilization is increased during repeated bouts of exercise, but the underlying
      mechanisms involved in this process have not yet been delineated. The relative
      involvement of catecholamine- and ANP-dependent pathways in the control of lipid
      mobilization during repeated bouts of exercise was thus investigated in
      subcutaneous adipose tissue (SCAT) by microdialysis. The study was performed in
      healthy males. Subjects performed two 45-min exercise bouts (E1 and E2) at 50% of
      their maximal oxygen uptake separated by a 60-min rest period. Extracellular
      glycerol concentration (EGC), reflecting SCAT lipolysis, was measured in a
      control probe perfused with Ringer solution and in two other probes perfused with
      either Ringer plus phentolamine (alpha(1/2)-AR antagonist) or Ringer plus both
      phentolamine and propranolol (beta-AR antagonist). Plasma epinephrine, plasma
      glycerol, and EGC were 1.7-, 1.6-, and 1.2-fold higher in E2 than in E1,
      respectively. Phentolamine potentiated exercise-induced EGC increase during E2
      only. Propranolol reduced the lipolytic rate during both E1 and E2 compared with
      the probe with phentolamine. Plasma ANP concentration increased more during E2
      than during E1 and was correlated with the increase in EGC in the probe
      containing phentolamine plus propranolol. The results suggest that ANP is
      involved in the control of lipolysis during exercise and that it contributes to
      stimulation of lipolysis during repeated bouts of exercise.

PMID- 16291574
TI  - Stimulation of gluconeogenesis by intravenous lipids in preterm infants: response
      depends on fatty acid profile.
AB  - In preterm infants, both hypo- and hyperglycemia are a frequent problem.
      Intravenous lipids can affect glucose metabolism by stimulation of
      gluconeogenesis by providing glycerol, which is a gluconeogenic precursor, and/or
      free fatty acids (FFA), which are stimulants of the rate of gluconeogenesis. In
      25 preterm infants, glucose production and gluconeogenesis were measured using
      stable isotope techniques during a 6-h infusion of glucose only, glucose plus
      glycerol, or glucose plus an intravenous lipid emulsion. Two lipid emulsions
      differing in FFA composition were used: Intralipid ( approximately 60%
      polyunsaturated FFA) and Clinoleic (approximately 60% monounsaturated FFA). The
      rate of glucose infusion was 22 micromol x kg(-1) x min(-1) in all groups. During
      the study infusion, the FFA concentrations were higher in both lipid groups vs.
      the glycerol group (P < 0.001). Compared with baseline, the glucose production
      rate increased in the Intralipid group, whereas it decreased in the other groups
      (P = 0.002) due to a significant increase in gluconeogenesis in the Intralipid
      group (P = 0.016). The plasma glucose concentration was significantly higher
      during Intralipid infusion vs. the other groups (P = 0.046). Our conclusion was
      that Intralipid enhanced glucose production by increasing gluconeogenesis in
      preterm infants. This can be ascribed to the stimulatory effect of FFA in
      addition to any effect of glycerol alone. The lack of stimulation of
      gluconeogenesis in the Clinoleic vs. the Intralipid group suggests that different
      classes of fatty acids exert different effects on glucose kinetics in preterm
      infants.

PMID- 16291575
TI  - Protection against cisplatin-induced nephrotoxicity by a carbon monoxide
      releasing molecule.
AB  - Nephrotoxicity is one of the main side effects caused by cisplatin (CP), a widely
      used antineoplastic agent. Here, we examined the effect of a novel water-soluble
      carbon monoxide-releasing molecule (CORM-3) on CP-mediated cytotoxicity in renal
      epithelial cells and explored the potential therapeutic benefits of carbon
      monoxide in CP-induced nephrotoxicity in vivo. Exposure of LLC-PK(1) cells to CP
      (50 microM) caused significant apoptosis as evidenced by caspase-3 activation and
      an increased number of floating cells. Treatment with CORM-3 (1-50 microM)
      resulted in a remarkable and concentration-dependent decrease in CP-induced
      caspase-3 activity and cell detachment. This effect involved activation of the
      cGMP pathway as 1H-oxadiazole [4, 3-a] quinoxaline-1-ore (ODQ), a guanylate
      cyclase inhibitor, completely abolished the protection elicited by CORM-3. Using
      a rat model of CP-induced renal failure, we found that treatment with CP (7.5
      mg/kg) caused a significant elevation in plasma urea (6.6-fold) and creatinine
      (3.1-fold) levels, which was accompanied by severe morphological changes and
      marked apoptosis in tubules at the corticomedullary junction. A daily
      administration of CORM-3 (10 mg/kg ip), starting 1 day before CP treatment and
      continuing for 3 days thereafter, resulted in amelioration of renal function as
      shown by reduction of urea and creatinine levels to basal values, a decreased
      number of apoptotic tubular cells, and an improved histological profile. A
      negative control (iCORM-3) that is incapable of liberating CO failed to prevent
      renal dysfunction mediated by CP, indicating that CO is directly involved in
      renoprotection. Our data demonstrate that CORM-3 can be used as an effective
      therapeutic adjuvant in the treatment of CP-induced nephrotoxicity.

PMID- 16291576
TI  - The human organic anion transporter 3 (OAT3; SLC22A8): genetic variation and
      functional genomics.
AB  - The human organic anion transporter, OAT3 (SLC22A8), plays a critical role in
      renal drug elimination, by mediating the entry of a wide variety of organic
      anions, including a number of commonly used pharmaceuticals, into the renal
      proximal tubular cells. To understand the nature and extent of genetic variation
      in OAT3, and to determine whether such variation affects its function, we
      identified OAT3 variants in a large, ethnically diverse sample population and
      studied their transport activities in cellular assays. We identified a total of
      10 distinct coding-region variants, which altered the encoded amino acid
      sequence, in DNA samples from 270 individuals (80 African-Americans, 80 European
      Americans, 60 Asian-Americans, and 50 Mexican-Americans). The overall prevalence
      of these OAT3 variants was relatively low among the screened population, with
      only three variants having allele frequencies of >1% in a particular ethnic
      group. Clones of each variant were created by site-directed mutagenesis,
      expressed in HEK-293 cells, and tested for function using the model substrates,
      estrone sulfate (ES) and cimetidine (CIM). The results revealed a high degree of
      functional heterogeneity among OAT3 variants, with three variants (p. Arg149Ser,
      p. Gln239Stop, and p. Ile260Arg) that resulted in complete loss of function, and
      several others with significantly reduced function. One of the more common
      variants (p. Ile305Phe), found in 3.5% of Asian-Americans, appeared to have
      altered substrate specificity. This variant exhibited a reduced ability to
      transport ES, but a preserved ability to transport CIM. These data suggest that
      genetic variation in OAT3 may contribute to variation in the disposition of
      drugs.

PMID- 16291577
TI  - Activity of the renal Na+-K+-2Cl- cotransporter is reduced by mutagenesis of N
      glycosylation sites: role for protein surface charge in Cl- transport.
AB  - The renal-specific Na(+)-K(+)-2Cl(-) cotransporter NKCC2 belongs to the SLC12
      gene family; it is the target for loop diuretics and the cause of type I
      Bartter's syndrome. Because the NKCC2 sequence contains two putative N-linked
      glycosylation sites, one of which is conserved with the renal Na(+)-Cl(-)
      cotransporter in which glycosylation affects thiazide affinity, we assessed the
      role of glycosylation on NKCC2 functional properties. One (N442Q or N452Q) or
      both (N442,452Q) N-glycosylation sites were eliminated by site-directed
      mutagenesis. Wild-type NKCC2 and mutant clones were expressed in Xenopus laevis
      oocytes and analyzed by (86)Rb(+) influx, Western blotting, and confocal
      microscopy. Inhibition of glycosylation with tunicamycin in wild-type NKCC2
      injected oocytes resulted in an 80% reduction of NKCC2 activity. Immunoblot of
      injected oocytes revealed that glycosylation of NKCC2 was completely prevented in
      N442,452Q-injected oocytes. Functional activity was reduced by 50% in N442Q- and
      N452Q-injected oocytes and by 80% in oocytes injected with N442,452Q, whereas
      confocal microscopy of oocytes injected with wild-type or mutant enhanced green
      fluorescent protein-tagged NKCC2 clones revealed that surface fluorescence
      intensity was reduced approximately 20% in single mutants and 50% in the double
      mutant. Ion transport kinetic analyses revealed no changes in cation affinity and
      a small increase in Cl(-) affinity by N442Q and N442,452Q. However, a slight
      decrease in bumetanide affinity was observed. Our data demonstrate that NKCC2 is
      glycosylated and suggest that prevention of glycosylation reduces its functional
      expression by affecting insertion into the plasma membrane and the intrinsic
      activity of the cotransporter.

PMID- 16291578
TI  - Molecular stool testing for the early detection of colorectal cancer: swan song
      for p53?

PMID- 16291579
TI  - Pregnancy on imatinib: fatal outcome with meningocele.

PMID- 16291580
TI  - Gene expression profile of cytokines and chemokines in microdissected primary
      Hodgkin and Reed-Sternberg (HRS) cells: high expression of interleukin-11
      receptor alpha.
AB  - We microdissected Hodgkin and Reed-Sternberg (HRS) cells from 14 Hodgkin's
      lymphoma tissue samples (nodular sclerosis = 5; mixed cellularity = 9), and after
      isolation and amplification of mRNA, analyzed the expression profile of 140 genes
      of chemokines, cytokines and their receptors by cDNA microarray methods. We also
      compared the profile with those of germinal center (GC) cells in reactive
      lymphadenitis. Unsupervised clustering revealed a relatively homogeneous
      expression profile in HRS cells. HRS cells tended to express mainly Th2 T cell
      associated molecules rather than those of Th1, compared with GC cells.
      Interleukin-11 receptor alpha (IL-11Ralpha), a previously unknown HRS cell
      specific gene, was detected in addition to known genes. Immunohistochemical
      staining confirmed the expression of IL-11Ralpha at the protein level. In
      contrast, only few cases were positive for IL-11Ralpha in B cell lymphoma,
      diffuse large cell lymphoma and follicular lymphoma. This is the first analysis
      report of tissue HRS cells with cDNA microarray technique.

PMID- 16291581
TI  - Pleural tumors as sole primary manifestation of acute promyelocytic leukemia.

PMID- 16291582
TI  - Oxaliplatin-based chemotherapy in association with highly active antiretroviral
      therapy in metastatic colorectal cancer HIV-infected patients.

PMID- 16291583
TI  - Short-time infusion of oxaliplatin in combination with capecitabine (XELOX30) as
      second-line therapy in patients with advanced colorectal cancer after failure to
      irinotecan and 5-fluorouracil.
AB  - BACKGROUND: The efficacy of oxaliplatin combined with capecitabine (XELOX) as
      second-line therapy in patients with advanced colorectal cancer (ACRC) resistant
      to irinotecan is not well established. Oxaliplatin induces acute, cold-induced
      neuropathy in most patients. The incidence is claimed to be infusion rate
      dependent and therefore a 2-h infusion is recommended. PATIENTS AND METHODS: For
      practical and economic reasons, but also for patient's convenience, we performed
      a phase II study to examine XELOX30 (capecitabine 1000 mg/m2 orally twice daily
      on days 1-14 and oxaliplatin 130 mg/m2 as a 30 min infusion on day 1) in patients
      with ACRC resistant to irinotecan. In addition the pharmacokinetics of
      oxaliplatin was studied. RESULTS: From November 2002 to September 2003, 70
      patients with ACRC were treated with XELOX30. Median age was 62 (range 33-74
      years) years and median performance status was 1 (range 0-2). The median number
      of courses was four (range 1-12) and median cumulative dose of oxaliplatin was
      530 (range 125-1560) mg/m2. The response rate was 17% (95% CI 10-23), median time
      to progression (TTP) was 5.4 months (95% CI 4.6-6.4) and median survival 9.5
      months (95% CI 8.5-11.2). White blood cell count (WBC) and performance status
      were significantly correlated to TTP. Neurotoxicity was moderate: grade 1 56%,
      grade 2 17% and grade 3 6%. Other grade 3 toxicities were nausea/vomiting 9%,
      diarrhoea 14% and PPE 8%. The maximum blood concentration and total body
      clearance of oxaliplatin was higher than previously reported in studies examining
      2-h infusions, but the volume of distribution and terminal half-life was in close
      agreement with previous results. CONCLUSION: XELOX30 is a very convenient second
      line regimen in ACRC with an activity and safety profile similar to other
      oxaliplatin schedules.

PMID- 16291584
TI  - High-dose chemotherapy as adjuvant treatment for high-risk primary breast cancer
      patients.

PMID- 16291585
TI  - Vinorelbine and prednisone in frail elderly patients with intermediate-high grade
      non-Hodgkin's lymphomas.

PMID- 16291586
TI  - Dealing with metastatic breast cancer in elderly women: results from a French
      study on a large cohort carried out by the 'Observatory on Elderly Patients'.
AB  - BACKGROUND: Treatment of elderly patients with metastatic breast cancer (MBC) is
      not clearly defined and seems to vary according to the subjective appreciation of
      the physician. PATIENTS AND METHODS: After interviewing 107 French specialists
      qualified in oncology, data concerning 1009 MBC patients were collected: 500
      patients were between 65 and 74 years and 509 were >75 years of age. Differences
      in diagnosis and treatment strategy were analyzed for both age groups to identify
      the physician's criteria of choice and the eventual use of the geriatric
      assessment among those criteria. RESULTS: At diagnosis, synchronous metastatic
      disease was more frequent in patients over 75 years old (52% versus 39%;
      P<0.001). Physicians indicated that treatment was based on age and on a
      subjective evaluation of the patient's general status. Sixty-eight per cent of
      younger patients and only 31% of older ones received chemotherapy (P<0.001). In
      the older group drug doses were lower than those usually recommended in three
      quarters of cases. Only 10% of physicians considered that they under-treat
      patients using the FEC 50 regimen. Over 75 years of age, hormone therapy was
      offered to most patients, including 8% with hormone-independent tumors. Geriatric
      covariates were never considered. Geriatricians rarely, if ever, played a role in
      the therapeutic decision. CONCLUSIONS: Inclusion of elderly patients with MBC in
      prospective trials is warranted to define standards of care and reduce
      heterogeneity in the decision-making process.

PMID- 16291587
TI  - Absence of beta7 integrin results in less graft-versus-host disease because of
      decreased homing of alloreactive T cells to intestine.
AB  - The alpha4beta7 integrin plays a central role in the homing of T cells to the
      gut. We hypothesized that absence of the beta7 subunit would result in a
      reduction of intestinal graft-versus-host disease (GVHD) and an improvement in
      overall GVHD morbidity and mortality in recipients of hematopoietic stem cell
      transplantation (HSCT). Analysis of alloreactive beta7-/- T cells showed intact
      activation, proliferation, cytokine production, and cytotoxicity. However,
      recipients of beta7-/- donor T cells in murine HSCT models experienced less GVHD
      morbidity and mortality than recipients of wild-type (WT) T cells, associated
      with a decrease in donor T-cell infiltration of the liver and intestine and with
      an overall significant decrease in hepatic and intestinal GVHD. In graft-versus
      tumor (GVT) experiments, we demonstrated intact or even enhanced GVT activity of
      beta7-/- donor T cells. In conclusion, beta7-/- donor T cells caused less GVHD
      morbidity and mortality than WT donor T cells because of selectively decreased T
      cell infiltration of the liver and intestines. Our data suggest that strategies
      to target the beta7 integrin have the clinical potential to alleviate or prevent
      GVHD while sparing or potentiating GVT activity.

PMID- 16291588
TI  - The hematopoietic stem compartment consists of a limited number of discrete stem
      cell subsets.
AB  - Hematopoietic stem cells (HSCs) display extensive heterogeneity in their behavior
      even when isolated as phenotypically homogeneous populations. It is not clear
      whether this heterogeneity reflects inherently diverse subsets of HSCs or a
      homogeneous population of HSCs diversified by their response to different
      external stimuli. To address this, we analyzed 97 individual HSCs in long-term
      transplantation assays. HSC clones were obtained from unseparated bone marrow
      (BM) through limiting dilution approaches. Following transplantation into
      individual hosts, donor-type cells in blood were measured bimonthly and the
      resulting repopulation kinetics were grouped according to overall shape. Only 16
      types of repopulation kinetics were found among the HSC clones even though
      combinatorially 54 groups were possible. All HSC clones, regardless of their
      origin, could be assigned to this subset of groups, and the probability of
      finding new patterns is negligible. Thus, the full repertoire of repopulating
      HSCs was covered. These data indicate that the HSC compartment consists of a
      limited number of distinct HSC subsets, each with predictable behavior.
      Enrichment of HSCs (Lin- Rho- SP) changes the representation of HSC types by
      selecting for distinct subsets of HSCs. These data from the steady-state HSC
      repertoire could provide a basis for the diagnosis of perturbed patterns of HSCs
      potentially caused by disease or aging.

PMID- 16291589
TI  - Tumor evasion of the immune system: inhibiting p38 MAPK signaling restores the
      function of dendritic cells in multiple myeloma.
AB  - Dendritic cells (DCs) from patients with cancer are functionally defective, but
      the molecular mechanisms underlying these defects are poorly understood. In this
      study, we used the murine 5TGM1 myeloma model to examine the effects and
      mechanisms of tumor-derived factors on the differentiation and function of DCs.
      Myeloma cells or tumor culture conditioning medium (TCCM) were shown to inhibit
      the differentiation and function of BM-derived DCs (BMDCs), as evidenced by the
      down-regulated expression of DC-related surface molecules, decreased IL-12, and
      compromised capacity of the cells to activate allospecific T cells. Moreover,
      TCCM-treated BMDCs were inferior to normal BMDCs at priming tumor-specific immune
      responses in vivo. Neutralizing antibodies against IL-6, IL-10, and TGF-beta
      partially abrogated the effects. TCCM treatment activated p38 mitogen-activated
      protein kinase (MAPK) and Janus kinase (JNK) but inhibited extracellular
      regulated kinase (ERK). Inhibiting p38 MAPK restored the phenotype, cytokine
      secretion, and function of TCCM-treated BMDCs. BMDCs from cultures with TCCM and
      p38 inhibitor was as efficacious as normal BMDCs at inducing tumor-specific
      antibody, type 1 T cell, and cytotoxic T lymphocyte (CTL) responses and at
      prolonging mouse survival. Thus, our results suggested that tumor-induced p38
      MAPK activation and ERK inhibition in DCs may be a new mechanism for tumor
      evasion and that regulating these pathways during DC differentiation provides new
      strategies for generating potent DC vaccines for immunotherapy in patients with
      cancer.

PMID- 16291590
TI  - Role of melanotransferrin in iron metabolism: studies using targeted gene
      disruption in vivo.
AB  - Melanotransferrin (MTf) or tumor antigen p97 is a transferrin homolog that binds
      one iron (Fe) atom and has been suggested to play roles in a variety of
      processes, including Fe metabolism, eosinophil differentiation, and plasminogen
      activation. Considering the vital role of Fe in many metabolic pathways, such as
      DNA and heme synthesis, it is important to understand the function of MTf. To
      define this, a MTf knockout (MTf-/-) mouse was generated through targeted
      disruption of the MTf gene. The MTf-/- mice were viable and fertile and developed
      normally, with no morphologic or histologic abnormalities. Assessment of Fe
      indices, tissue Fe levels, hematology, and serum chemistry parameters
      demonstrated no differences between MTf-/- and wild-type (MTf+/+) mice,
      suggesting MTf was not essential for Fe metabolism.

PMID- 16291591
TI  - Multiplicity and plasticity of natural killer cell signaling pathways.
AB  - Natural killer (NK) cells express an array of activating receptors that associate
      with DAP12 (KARAP), CD3zeta, and/or FcRgamma ITAM (immunoreceptor tyrosine-based
      activation motif)-bearing signaling subunits. In T and mast cells, ITAM-dependent
      signals are integrated by critical scaffolding elements such as LAT (linker for
      activation of T cells) and NTAL (non-T-cell activation linker). Using mice that
      are deficient for ITAM-bearing molecules, LAT or NTAL, we show that NK cell
      cytotoxicity and interferon-gamma secretion are initiated by ITAM-dependent and 
      independent as well as LAT/NTAL-dependent and -independent pathways. The role of
      these various signaling circuits depends on the target cell as well as on the
      activation status of the NK cell. The multiplicity and the plasticity of the
      pathways that initiate NK cell effector functions contrast with the situation in
      T cells and B cells and provide an explanation for the resiliency of NK cell
      effector functions to various pharmacologic inhibitors and genetic mutations in
      signaling molecules.

PMID- 16291592
TI  - KIT mutations, and not FLT3 internal tandem duplication, are strongly associated
      with a poor prognosis in pediatric acute myeloid leukemia with t(8;21): a study
      of the Japanese Childhood AML Cooperative Study Group.
AB  - Patients with t(8;21) acute myeloid leukemia (AML) are considered to have a good
      prognosis; however, approximately 50% of them relapse. The genetic alterations
      associated with a poor outcome in t(8;21) AML remain unknown. Recently,
      aberrations of receptor tyrosine kinases (RTKs) were frequently found in patients
      with AML. However, the prevalence and prognostic impact of RTK aberrations in
      pediatric t(8;21) AML remains undetermined. Here, we found the kinase domain
      mutations of the KIT gene in 8 (17.4%) of 46 patients with t(8;21) AML among
      newly diagnosed pediatric patients with AML treated on the AML99 protocol in
      Japan. Significant differences between patients with or without KIT mutations
      were observed in the 4-year overall survival (50.0% versus 97.4%, P = .001),
      disease-free survival (37.5% versus 94.7%, P < .001) and relapse rate (47.0%
      versus 2.7%, P < .001). Furthermore, FLT3 internal tandem duplication was found
      in only 2 (4.3%) patients. These results suggested that KIT mutations are
      strongly associated with a poor prognosis in pediatric t(8;21) AML.

PMID- 16291593
TI  - Recent insights into the role of Notch signaling in tumorigenesis.
AB  - Members of the Notch family of transmembrane receptors play an important role in
      cell fate determination. Over the past decade, a role for Notch in the
      pathogenesis of hematologic and solid malignancies has become apparent. Numerous
      cellular functions and microenvironmental cues associated with tumorigenesis are
      modulated by Notch signaling, including proliferation, apoptosis, adhesion,
      epithelial-to-mesenchymal transition, and angiogenesis. It is becoming
      increasingly evident that Notch signaling can be both oncogenic and tumor
      suppressive. This review highlights recent findings regarding the molecular and
      functional aspects of Notch-mediated neoplastic transformation. In addition,
      cellular mechanisms that potentially explain the complex role of Notch in
      tumorigenesis are discussed.

PMID- 16291594
TI  - Adaphostin-induced oxidative stress overcomes BCR/ABL mutation-dependent and 
      independent imatinib resistance.
AB  - The BCR/ABL kinase has been targeted for the treatment of chronic myelogenous
      leukemia (CML) by imatinib mesylate. While imatinib has been extremely effective
      for chronic phase CML, blast crisis CML and Ph+ acute lymphoblastic leukemia
      (ALL) are often resistant. In particular, mutation of the T315 residue in the
      bcr/abl activation loop renders cells highly resistant to imatinib and to second
      generation kinase inhibitors such as BMS-354825 or AMN107. Adaphostin is a
      tyrphostin that was originally intended to inhibit the BCR/ABL kinase by
      competing with its peptide substrates. Recent findings have in addition
      implicated reactive oxygen species (ROS) in the cytotoxic mechanism of
      adaphostin. In view of this unique mode of action, we examined the effects of
      adaphostin on numerous imatinib-resistant leukemia models, including imatinib
      resistant CML and Ph+ ALL cell lines, cells harboring point mutations in BCR/ABL,
      and specimens from imatinib-resistant CML patients, using assays for
      intracellular ROS, apoptosis, and clonogenicity. Every model of imatinib
      resistance examined remained fully sensitive to adaphostin-induced cell death.
      Collectively, these data suggest that ROS generation by adaphostin overcomes even
      the most potent imatinib resistance in CML and Ph+ ALL.

PMID- 16291596
TI  - Apaf-1 and caspase-9 are required for cytokine withdrawal-induced apoptosis of
      mast cells but dispensable for their functional and clonogenic death.
AB  - Cytokines promote survival of mast cells by inhibiting apoptotic pathways
      regulated by the Bcl-2 protein family. We previously showed that lymphocyte
      apoptosis can proceed via a Bcl-2-inhibitable pathway independent of the
      canonical initiator caspase, caspase-9, and its adaptor, Apaf-1. Here we report
      that mast cells lacking caspase-9 or Apaf-1 are refractory to apoptosis after
      cytotoxic insults but still lose effector function and ability to proliferate. In
      response to cytokine deprivation or DNA damage, fetal liver-derived mast cells
      lacking Apaf-1 or caspase-9 failed to undergo apoptosis. Nevertheless, the
      cytokine-starved cells were not functionally alive, because, unlike those
      overexpressing Bcl-2, they could not degranulate on Fcepsilon receptor
      stimulation or resume proliferation on re-addition of cytokine. Furthermore, mast
      cells lacking Apaf-1 or caspase-9 had no survival advantage over wild-type
      counterparts in vivo. These results indicate that the Apaf-1/caspase-9
      independent apoptotic pathway observed in lymphocytes is ineffective in cytokine
      deprived mast cells. However, although Apaf-1 and caspase-9 are essential for
      mast cell apoptosis, neither is required for the functional or clonogenic death
      of the cells, which may be due to mitochondrial dysfunction.

PMID- 16291595
TI  - Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide
      resistance, priapism, leg ulceration, pulmonary hypertension, and death in
      patients with sickle cell disease.
AB  - Pulmonary hypertension is prevalent in adult patients with sickle cell disease
      and is strongly associated with early mortality and markers of hemolysis, in
      particular, serum lactate dehydrogenase (LDH). Intravascular hemolysis leads to
      impaired bioavailability of nitric oxide (NO), mediated by NO scavenging by
      plasma oxyhemoglobin and by arginine degradation by plasma arginase. We
      hypothesized that serum LDH may represent a convenient biomarker of intravascular
      hemolysis and NO bioavailability, characterizing a clinical subphenotype of
      hemolysis-associated vasculopathy. In a cohort of 213 patients with sickle cell
      disease, we found statistically significant associations of steady-state LDH with
      low levels of hemoglobin and haptoglobin and high levels of reticulocytes,
      bilirubin, plasma hemoglobin, aspartate aminotransferase, arginase, and soluble
      adhesion molecules. LDH isoenzyme fractionation confirmed predominance of LD1 and
      LD2, the principal isoforms within erythrocytes. In a subgroup, LDH levels
      closely correlated with plasma cell-free hemoglobin, accelerated NO consumption
      by plasma, and impaired vasodilatory responses to an NO donor. Remarkably, this
      simple biomarker was associated with a clinical subphenotype of pulmonary
      hypertension, leg ulceration, priapism, and risk of death in patients with sickle
      cell disease. We propose that LDH elevation identifies patients with a syndrome
      of hemolysis-associated NO resistance, endothelial dysfunction, and end-organ
      vasculopathy.

PMID- 16291597
TI  - Species- and cell type-specific interactions between CD47 and human SIRPalpha.
AB  - CD47 on red blood cells (RBCs) reportedly signals "self" by binding SIRPalpha on
      phagocytes, at least in mice. Such interactions across and within species, from
      mouse to human, are not yet clear and neither is the relation to cell adhesion.
      Using human SIRPalpha1 as a probe, antibody-inhibitable binding to CD47 was found
      only with human and pig RBCs (not mouse, rat, or cow). In addition, CD47-mediated
      adhesion of human and pig RBCs to SIRPalpha1 surfaces resists sustained forces in
      centrifugation (as confirmed by atomic force microscopy) but only at SIRPalpha
      coating densities far above those measurable on human neutrophils, monocytes, and
      THP-1 macrophages. While interactions strengthen with deglycosylation of
      SIRPalpha1, low copy numbers explain the absence of RBC adhesion to phagocytes
      under physiologic conditions and imply that the interaction being studied is not
      responsible for red cell clearance in humans. Evidence of clustering nonetheless
      suggests mechanisms of avidity enhancement. Finally, using the same CD47
      antibodies and soluble SIRPalpha1, bone marrow-derived mesenchymal stem cells
      were assayed and found to display CD47 but not bind SIRPalpha1 significantly. The
      results thus demonstrate that SIRPalpha-CD47 interactions, which reportedly
      define self, exhibit cell type specificity and limited cross-species reactivity.

PMID- 16291598
TI  - Tolerance induction by lentiviral gene therapy with a nonmyeloablative regimen.
AB  - Antibodies (Abs) directed at the Gal alpha1,3Gal beta1,4GlcNAc-R (alphaGal)
      carbohydrate epitope initiate xenograft rejection. Previously, we have shown that
      bone marrow transplantation (BMT) with lentivirus-mediated gene transfer of
      porcine alpha1,3 galactosyltransferase (GalT) is able to induce tolerance to
      alphaGal-expressing heart grafts following a lethal dose of irradiation. Here we
      show the first demonstration of permanent survival of alphaGal+ hearts following
      transplantation with autologous, lentivirus-transduced BM using a
      nonmyeloablative regimen. Autologous BM from GalT knockout (GalT-/-) mice was
      transduced with a lentiviral vector expressing porcine GalT and transplanted into
      sublethally irradiated (3 Gy) GalT-/- mice. Chimerism in the peripheral blood
      cells (PBCs) remained low but was higher in the BM, especially within the stromal
      cell population. Mice reconstituted with GalT did not produce anti-alphaGal Abs
      over time. We immunized these mice with alphaGal-expressing cells and assessed
      humoral immune responses. Anti-alphaGal xenoantibodies were not produced in mice
      reconstituted with GalT, but normal Ab responses to other xenoantigens were
      detected. Mice reconstituted with GalT accepted alphaGal+ heart grafts over 100
      days. Transduction with lentiviral vectors results in chimerism at levels
      sufficient to induce long-term tolerance under nonmyeloablative conditions.

PMID- 16291599
TI  - Reduced retention of radioprotective hematopoietic cells within the bone marrow
      microenvironment in CXCR4-/- chimeric mice.
AB  - The physiologic role of CXCR4 on hematopoietic stem/progenitor cells (HSPCs) is
      not fully understood. Here, we show that radioprotection of lethally irradiated
      mice by embryonic day 14.5 (E14.5) CXCR4-/- fetal liver (FL) cells was markedly
      impaired when compared with CXCR4+/+ counterparts, but this defect was rescued
      when hosts were engrafted with high cell numbers. This quantitative defect
      contrasted with a similar content in hematopoietic colony-forming cells (CFCs),
      splenic colony-forming units (CFUs-S), and Lin- Sca-1+ c-kit+ cells in E14.5
      CXCR4-/- and CXCR4+/+ livers. In addition, the homing of HSPCs in the bone marrow
      was not altered as detected with a CFSE-staining assay. In contrast, a 30-fold
      increase in CFCs was seen in the circulation of mice stably reconstituted with
      CXCR4-/- FL cells and this increment was already observed before hematopoiesis
      had reached a steady-state level. Together, the data strongly suggest that
      impaired retention may, at least in short-term hematopoietic reconstitution, lead
      to a diminution in the number of available progenitors required for
      radioprotection.

PMID- 16291600
TI  - Evaluation of the efficacy and safety of etoricoxib in the treatment of
      hemophilic arthropathy.
AB  - This 2-part, double-blind, placebo-controlled study was conducted to determine
      the safety and efficacy of etoricoxib, a COX-2 selective inhibitor, for the
      treatment of hemophilic arthropathy. In part 1 (6 weeks), 102 patients (> or = 12
      years old) with hemophilic arthropathy were randomized to receive 90 mg
      etoricoxib once daily or placebo (1:1 ratio). In part 2 (6 months), 51 patients
      taking placebo in part 1 were randomized to receive 90 mg etoricoxib or 25 mg
      rofecoxib once daily; patients taking etoricoxib in part 1 continued the same
      treatment. Efficacy end points included Patient Assessment of Arthropathy Pain,
      Patient Global Assessment of Arthropathy Disease Status, and Investigator Global
      Assessment of Arthropathy Disease Status. Safety was evaluated at each study
      visit. Etoricoxib provided significant improvement in all end points versus
      placebo (P < .001). Fewer patients taking etoricoxib discontinued due to a lack
      of efficacy versus placebo (P = .048). During part 2, efficacy was maintained;
      etoricoxib and rofecoxib demonstrated similar results. The most common adverse
      experiences were upper respiratory infection and headache. The incidence of joint
      bleeding during part 1 was similar between etoricoxib (66.7%) and placebo (72.6%)
      and during part 2 between etoricoxib (77.0%) and rofecoxib (78.9%). We conclude
      that etoricoxib provided superior efficacy versus placebo for the treatment of
      hemophilic arthropathy and was generally safe and well tolerated.

PMID- 16291601
TI  - Angiographic and clinical outcomes in patients receiving low-molecular-weight
      heparin versus unfractionated heparin in ST-elevation myocardial infarction
      treated with fibrinolytics in the CLARITY-TIMI 28 Trial.
AB  - BACKGROUND: Low-molecular-weight heparin (LMWH) offers pharmacological and
      practical advantages over unfractionated heparin (UFH). Whether these advantages
      translate into greater infarct-related artery patency and fewer adverse clinical
      events in patients with ST-elevation myocardial infarction (STEMI) receiving
      fibrinolytic therapy remains under study. METHODS AND RESULTS: We compared
      angiographic and clinical outcomes in patients treated with LMWH (n=1429) versus
      UFH (n=1431) in CLARITY-TIMI 28, a randomized trial of clopidogrel versus placebo
      in STEMI patients aged 18 to 75 years undergoing fibrinolysis. After
      comprehensive adjustment for baseline characteristics, therapeutic interventions,
      and a propensity score, treatment with LMWH was associated with a significantly
      lower rate of a closed infarct-related artery or death or myocardial infarction
      before angiography (13.5% versus 22.5%, adjusted OR 0.76, P=0.027). Treatment
      with LMWH was also associated with a significantly lower rate of cardiovascular
      death or recurrent myocardial infarction through 30 days (6.9% versus 11.5%,
      adjusted OR 0.68, P=0.030). The lower event rates were observed in patients
      allocated to clopidogrel and in those who underwent percutaneous coronary
      intervention. Rates of TIMI major bleeding through 30 days (1.6% versus 2.2%,
      P=0.27) and intracranial hemorrhage (0.6% versus 0.8%, P=0.37) were similar in
      the LMWH and UFH groups. Patients who received both clopidogrel and LMWH, in
      addition to a standard fibrinolytic and aspirin, had a particularly high rate of
      infarct-related artery patency (90.9%) and particularly low rates of
      cardiovascular death (3.2%), recurrent myocardial infarction (3.0%), and major
      bleeding (1.8%). CONCLUSIONS: In patients with STEMI receiving fibrinolytic
      therapy, use of LMWH with other standard therapies, including clopidogrel and
      aspirin, is associated with improved angiographic outcomes and lower rates of
      major adverse cardiovascular events.

PMID- 16291602
TI  - Reply to: "Letter to the Editor: concerning an article comparing the efficacy of
      local and systemic treatment of clinical mastitis".

PMID- 16291603
TI  - Letter to the editor: comments on a recent article by Burgos et al.

PMID- 16291604
TI  - Improvement of functional properties of whey protein isolate through glycation
      and phosphorylation by dry heating.
AB  - Whey protein isolate (WPI) was glycated with maltopentaose (MP) through the
      Maillard reaction, and the MP-conjugated WPI (MP-WPI) was then phosphorylated by
      dry heating in the presence of pyrophosphate. Glycation occurred efficiently, and
      the sugar content of WPI increased approximately 19.9% through the Maillard
      reaction. The phosphorylation of MP-WPI was enhanced with an increase in the dry
      heating time from 1 to 5 d, and the phosphorus content of WPI increased
      approximately 1.05% by dry heating at pH 4.0 and 85 degrees C for 5 d in the
      presence of pyrophosphate. The electrophoretic mobility of WPI increased with an
      increase in the phosphorylation level. The stability of WPI against heat-induced
      insolubility at pH 7.0 was improved by conjugation with MP alone, and further
      improved by phosphorylation. Although the emulsifying activity of WPI was barely
      affected by glycation and phosphorylation, the emulsifying stability of
      phosphorylated MP-WPI (5 d), was 2.2 times higher than that of MP-WPI. Gelling
      properties such as hardness, resiliency, and water-holding capacity of heat
      induced WPI gel were markedly improved, and the gel was rendered transparent by
      phosphorylation. The calcium phosphate-solubilizing ability of WPI was enhanced
      by phosphorylation. These results suggested that phosphorylation by dry heating
      in the presence of pyrophosphate after conjugation with MP is a useful method for
      improving the functional properties of WPI.

PMID- 16291605
TI  - Comparison of the functionality of exopolysaccharides produced in situ or added
      as bioingredients on yogurt properties.
AB  - The effect on yogurt properties of in situ production of exopolysaccharides (EPS)
      and addition of 2 EPS powders (crude and purified EPS from Lactobacillus
      rhamnosus RW-9595M fermentation in whey-based medium) at different concentrations
      was studied. No effect of purified powder addition for EPS concentrations up to
      500 mg/L was observed on acidification rate to the difference of milks
      supplemented with crude EPS, which exhibited longer acidification times. The
      addition of EPS from 125 to 500 mg/L or the use of EPS-producing cultures
      resulted in yogurts with lower yield stress and viscoelastic moduli compared with
      control yogurts without EPS, with no apparent effect of EPS concentration.
      However, the consistency index was higher for yogurts produced with the
      commercial EPS-producing culture, and to a lesser extent with the mixed culture
      containing Lb. rhamnosus RW-9595M, compared with yogurts supplemented with EPS
      powders, which were not different from that for control yogurts. Our study showed
      that the mode of EPS incorporation in yogurts has a major effect on the
      rheological properties of the final product.

PMID- 16291606
TI  - Development and application of image analysis to quantify calcium lactate
      crystals on the surface of smoked Cheddar cheese.
AB  - Calcium lactate crystals that form white specks or haze on the surface of cheese
      constitute a significant quality problem for producers of Cheddar cheese.
      Subjective methods to evaluate crystal coverage of cheese surfaces have been
      reported previously, but objective methods are currently lacking. The objectives
      of this work were to develop and evaluate an objective method to measure the area
      occupied by calcium lactate crystals on surfaces of naturally smoked Cheddar
      cheese samples using digital photography and image analysis. Coefficients of
      variation ranged from 1.29 to 4.68% for 5 replicate analyses of 3 different
      cheese surfaces that ranged from approximately 2 to 49% of total surface area
      occupied by crystals. Thus, results showed a high degree of repeatability for the
      3 cheese surfaces, which ranged from very slight and geometrically simple to very
      heavy and geometrically complex crystal coverage. The method underestimated total
      area occupied by crystals on the 3 surfaces by 0.24 to 4.83% unless the fainter
      crystal regions that went undetected during initial thresholding were manually
      segmented and quantified. The wet weight of crystal substance collected per unit
      of surface area from 20 different cheese samples increased exponentially as the
      percentage of total surface area occupied by crystals increased. These data were
      consistent with subjective observations that crystal regions appeared to grow
      vertically as well as horizontally as they expanded to occupy greater surface
      area. Image analysis was well suited for evaluating changes in crystal coverage
      during cheese aging because measurements were made nondestructively and with
      minimal disruption to the cheese. The area occupied by crystals on 6 different
      surfaces from 3 different cheese samples increased linearly (R2 = 0.94 to 0.99)
      during storage at 4 degrees C for up to 33 wk. However, the rates of increase
      differed significantly among the 3 cheese samples. Image analysis may serve as a
      useful tool to quantitatively evaluate the effects of factors such as cheese
      composition, packaging conditions and storage temperature on rate of crystal
      growth and time of crystal appearance during storage.

PMID- 16291607
TI  - Interactions in biofilms of Lactococcus lactis ssp. cremoris and Pseudomonas
      fluorescens cultured in cold UHT milk.
AB  - Three Lactococcus lactis ssp. cremoris isolates from refrigerated bulk raw milk
      were cultured separately and in association with a known psychrotrophic dairy
      Pseudomonas fluorescens strain, in skim UHT milk for 72 h at 7 degrees C, to
      determine mutual influences in both the planktonic and biofilm phases. Two levels
      of inoculum of each culture partner were combined. Protocooperation and
      commensalism cases were found, all of them in the biofilm phase. Type and
      intensity of the interactions depended on Lactococcus strain and on the cell
      density of each partner. Maximum enhancement of attachment was observed to be
      approximately 100-fold for P. fluorescens and 20,000-fold for one of the L.
      lactis strains. Confocal scanning laser microscopy images show compact masses of
      Pseudomonas trapping lactococci cells in cooperative biofilms.

PMID- 16291608
TI  - Comparison of sensory, microbiological, and biochemical parameters of microwave
      versus indirect UHT fluid skim milk during storage.
AB  - Shelf-stable milk could benefit from sensory quality improvement. Current methods
      of heating cause flavor and nutrient degradation through exposure to overheated
      thermal exchange surfaces. Rapid heating with microwaves followed by sudden
      cooling could reduce or eliminate this problem. The objectives for this study
      were focused on designing and implementing continuous microwave thermal
      processing of skim fluid milks (white and chocolate) to compare sensory,
      microbiological, and biochemical parameters with conventionally prepared,
      indirect UHT milks. All test products were aseptically packaged and stored at
      ambient temperature for 12 mo. Every 3 mo, samples were taken for microbiological
      testing, reactive sulfhydryl determinations, active enzyme analysis, instrumental
      viscosity readings, color measurements, and descriptive sensory evaluation.
      Microbiological plate counts were negative on all milks at each time point.
      Enzymatic assays showed that plasmin was inactivated by both heat treatments.
      5,5'-dithio-bis(2-nitrobenzoic acid) analysis, a measure of reactive sulfhydryl (
      SH-) groups, showed that the initial thiol content was not significantly
      different between the microwave-processed and UHT-treated milks. However, both
      heating methods resulted in an increased thiol level compared with conventionally
      pasteurized milk samples due to the higher temperatures attained. Sulfhydryl
      oxidase, a milk enzyme that catalyzes disulfide bond formation using a variety of
      protein substrates, retained activity following microwave processing, and
      decreased during storage. Viscosity values were essentially equivalent in
      microwave- and UHT-heated white skim milks. Sensory analyses established that UHT
      treated milks were visibly darker, and exhibited higher caramelized and
      stale/fatty flavors with increased astringency compared with the microwave
      samples. Sweet aromatic flavor and sweet taste decreased during storage in both
      UHT and microwave milk products, whereas stale/fatty flavors increased over time.
      Sensory effects were more apparent in white milks than in chocolate varieties.
      These studies suggest that microwave technology may provide a useful alternative
      processing method for delivery of aseptic milk products that retain a long shelf
      life.

PMID- 16291609
TI  - Yield and aging of Cheddar cheeses manufactured from milks with different milk
      serum protein contents.
AB  - Whey proteins in general and specifically beta-lactoglobulin, alpha-lactalbumin,
      and immunoglobulins have been thought to decrease proteolysis in cheeses
      manufactured from concentrated retentates from ultrafiltration. The proteins
      found in whey are called whey proteins and are called milk serum proteins (SP)
      when they are in milk. The experiment included 3 treatments; low milk SP (0.18%),
      control (0.52%), and high milk SP (0.63%), and was replicated 3 times. The
      standardized milk for cheese making of the low milk SP treatment contained more
      casein as a percentage of true protein and more calcium as a percentage of crude
      protein, whereas the nonprotein nitrogen and total calcium content was not
      different from the control and high SP treatments. The nonprotein nitrogen and
      total calcium content of the milks did not differ because of the process used to
      remove the milk SP from skim milk. The low milk SP milk contained less free fatty
      acids (FFA) than the control and high milk SP treatment; however, no differences
      in FFA content of the cheeses was detected. Approximately 40 to 45% of the FFA
      found in the milk before cheese making was lost into the whey during cheese
      making. Decreasing the milk SP content of milk by 65% and increasing the content
      by 21% did not significantly influence general Cheddar cheese composition. Higher
      fat recovery and cheese yield were detected in the low milk SP treatment cheeses.
      There was more proteolysis in the low milk SP cheese and this may be due to the
      lower concentration of undenatured beta-lactoglobulin, alpha-lactalbumin, and
      other high molecular weight SP retained in the cheeses made from milk with low
      milk SP content.

PMID- 16291610
TI  - Application of exopolysaccharide-producing cultures in reduced-fat Cheddar
      cheese: composition and proteolysis.
AB  - Proteolysis during ripening of reduced fat Cheddar cheeses made with different
      exopolysaccharide (EPS)-producing and nonproducing cultures was studied. A ropy
      strain of Lactococcus lactis ssp. cremoris (JFR1) and capsule-forming nonropy and
      moderately ropy strains of Streptococcus thermophilus were used in making reduced
      fat Cheddar cheese. Commercial Cheddar starter was used in making full-fat
      cheese. Results showed that the actual yield of cheese made with JFR1 was higher
      than that of all other reduced-fat cheeses. Cheese made with JFR1 contained
      higher moisture, moisture in the nonfat substance, and residual coagulant
      activity than all other reduced-fat cheeses. Proteolysis, as determined by PAGE
      and the level of water-soluble nitrogen, was also higher in cheese made with JFR1
      than in all other cheeses. The HPLC analysis showed a significant increase in
      hydrophobic peptides (causing bitterness) during storage of cheese made with
      JFR1. Cheese made with the capsule-forming nonropy adjunct of S. thermophilus,
      which contained lower moisture and moisture in the nonfat substance levels and
      lower chymosin activity than did cheese made with JFR1, accumulated less
      hydrophobic peptides. In conclusion, some EPS-producing cultures produced reduced
      fat Cheddar cheese with moisture in the nonfat substance similar to that in its
      full-fat counterpart without the need for modifying the standard cheese-making
      protocol. Such cultures might accumulate hydrophobic (bitter) peptides if they do
      not contain the system able to hydrolyze them. For making high quality reduced
      fat Cheddar cheese, EPS-producing cultures should be used in conjunction with
      debittering strains.

PMID- 16291611
TI  - Application of exopolysaccharide-producing cultures in reduced-fat Cheddar
      cheese: texture and melting properties.
AB  - Textural, melting, and sensory characteristics of reduced-fat Cheddar cheeses
      made with exopolysaccharide (EPS)-producing and nonproducing cultures were
      monitored during ripening. Hardness, gumminess, springiness, and chewiness
      significantly increased in the cheeses as fat content decreased. Cheese made with
      EPS-producing cultures was the least affected by fat reduction. No differences in
      hardness, springiness, and chewiness were found between young reduced fat cheese
      made with a ropy Lactococcus lactis ssp. cremoris [JFR1; the culture that
      produced reduced-fat cheese with moisture in the nonfat substance (MNFS) similar
      to that in its full-fat counterpart] and its full-fat counterpart. Whereas
      hardness of full-fat cheese and reduced-fat cheese made with JFR1 increased
      during ripening, a significant decrease in its value was observed in all other
      cheeses. After 6 mo of ripening, reduced fat cheeses made with all EPS-producing
      cultures maintained lower values of all texture profile analysis parameters than
      did those made with no EPS. Fat reduction decreased cheese meltability. However,
      no differences in meltability were found between the young full-fat cheese and
      the reduced-fat cheese made with the ropy culture JFR1. Both the aged full- and
      reduced-fat cheeses made with JFR1 had similar melting patterns. When heated,
      they both became soft and creamy without losing shape, whereas reduced-fat cheese
      made with no EPS ran and separated into greasy solids and liquid. No differences
      were detected by panelists between the textures of the full-fat cheese and
      reduced-fat cheese made with JFR1, both of which were less rubbery or firm,
      curdy, and crumbly than all other reduced-fat cheeses.

PMID- 16291612
TI  - Application of exopolysaccharide-producing cultures in reduced-fat Cheddar
      cheese: cryo-scanning electron microscopy observations.
AB  - The microstructure of reduced- and full-fat Cheddar cheeses made with
      exopolysaccharide (EPS)-producing and nonproducing cultures was observed using
      cryo-scanning electron microscopy. Fully hydrated cheese samples were rapidly
      frozen in liquid nitrogen slush (-207 degrees C) and observed in their frozen
      hydrated state without the need for fat extraction. Different EPS-producing
      cultures were used in making reduced-fat Cheddar cheese. Full-fat cheese was made
      with a commercial EPS-nonproducing starter culture. The cryo-scanning electron
      micrographs showed that fat globules in the fully hydrated cheese were surrounded
      by cavities. Serum channels and pores in the protein network were clearly
      observed. Young (1-wk-old) full-fat cheese contained wide and long fat serum
      channels, which were formed because of fat coalescence. Such channels were not
      observed in the reduced-fat cheese. Young reduced-fat cheese made with EPS
      nonproducing cultures contained fewer and larger pores than did reduced-fat
      cheese made with a ropy strain of Lactococcus lactis ssp. cremoris (JFR1), which
      had higher moisture levels. A 3-dimensional network of EPS was observed in large
      pores in cheese made with JFR1. Major changes in the size and distribution of
      pores within the structure of the protein network were observed in all reduced
      fat cheeses, except that made with JFR1, as they aged. Changes in porosity were
      less pronounced in both the full-fat and the reduced-fat cheeses made with JFR1.

PMID- 16291613
TI  - Effects of exopolysaccharide-producing cultures on the viscoelastic properties of
      reduced-fat Cheddar cheese.
AB  - The objective was to study the influence of different exopolysaccharide (EPS)
      producing and nonproducing lactic cultures on the viscoelastic properties of
      reduced-fat Cheddar cheese. Changes in the viscoelastic properties were followed
      over a ripening period of 6 mo. Results showed that the elastic, viscous, and
      complex moduli were higher in reduced-fat cheeses made with EPS-nonproducing
      cultures than in full-fat cheese. No differences in the viscoelastic properties
      were found between young reduced-fat cheese made with a ropy strain of
      Lactococcus lactis ssp. cremoris (JFR1) and its full-fat counterpart.
      Interestingly, the changes in viscoelastic moduli in both full-fat cheese and
      reduced-fat cheese made with JFR1 during ripening followed the same pattern.
      Whereas the moduli increased during the first month of ripening in those 2
      cheeses, a dramatic decrease was observed in all other cheeses. Slopes of the
      viscoelastic moduli as a function of frequency were lower in the full-fat than in
      reduced-fat cheeses. The creep test showed that fresh reduced-fat cheese made
      with JFR1 was less rigid and more deformable than that made with EPS-nonproducing
      cultures. The creep and recovery properties of young reduced-fat cheese made with
      JFR1 and the full-fat type were similar. No differences were found in the
      viscoelastic properties between reduced-fat cheese made with no EPS and those
      made with EPS-producing adjunct cultures of Streptococcus thermophilus. After 6
      mo of ripening, cheeses made with EPS-producing cultures maintained lower elastic
      and viscous moduli than did those made with no EPS.

PMID- 16291614
TI  - Caseinomacropeptide self-association is dependent on whether the peptide is free
      or restricted in kappa-casein.
AB  - There is a general agreement that the experimentally determined molecular weight
      (MW) of caseinomacropeptide (CMP) is greater than the theoretical MW. Some
      studies suggest that this is due to a pH-dependent aggregation of monomeric CMP.
      How this aggregation is influenced by pH is not understood. This study was
      carried out to study the nature of CMP aggregates and to clarify which conditions
      affect aggregation of CMP. The apparent MW of CMP at different pH values was
      determined using size-exclusion chromatography. Caseinomacropeptide was further
      characterized by immunochemical analysis, sodium dodecyl sulfate-PAGE, N-terminal
      sequencing, and mass spectrometry. The hydrophobicity of CMP was studied by means
      of 1-anilino-naphthalene-8-sulfonic acid binding experiments. Four CMP products
      prepared by different methods were studied: CMP produced by enzymatic (chymosin
      or pepsin) hydrolysis of kappa-casein (CN), and 2 commercial CMP products. Both
      commercial products and CMP resulting from chymosin-hydrolysis of kappa-CN (at pH
      6.6) had elution volumes with a MW corresponding to 35 kDA at pH 8.0 and 3.4.
      Caseinomacropeptide prepared from pepsin-hydrolysis of kappa-CN (at pH 2.5)
      eluted as multiple peaks with apparent MW of 35, 18, and 9 kDa, again
      independently of pH. Hydrolysis of kappa-CN with chymosin or pepsin at different
      pH values (pH 2.5, 3.4, and 6.6) produced differently sized aggregates of CMP,
      largely depending on the pH of the hydrolysis. These results indicate that,
      whereas CMP molecules are irreversibly associated, CMP in kappa-CN may associate
      reversibly in a pH-dependent manner. We suggest that interactions between para
      kappa-CN parts of the kappa-CN molecules may be a requisite for the pH-dependent
      dissociation/association.

PMID- 16291615
TI  - Technical note: Direct enzyme immunoassay of progesterone in bovine milk whey.
AB  - A simple extraction-free or direct quantitative ELISA for progesterone in bovine
      milk whey was developed. Whey samples are easy to collect, transport, and store.
      This method also allows for monitoring progesterone levels in cattle, which is
      important in reproductive management. The assay was designed to cover the
      concentration range 0.05 to 2 ng/mL, and the sensitivity of the method was 1.5
      pg/mL. The intra- and interassay coefficients of variation were 8 and 12%,
      respectively. A high correlation (r = 0.90) between ELISA and radioimmunoassay
      measurements of progesterone in the same milk whey samples was obtained. The
      method can be easily applied in practice because samples can be stored at room
      temperature (22 to 26 degrees C) for 4 d. Moreover, because analysis requires
      milk coagulation, that process can be initiated during transport by standard mail
      services to the laboratory. Upon arrival at the laboratory, whey can be kept
      refrigerated for 1 wk before analysis. This tool is useful for monitoring luteal
      activity of dairy cows.

PMID- 16291616
TI  - A stochastic model simulating pathogen-specific mastitis control in a dairy herd.
AB  - The objective of this study was to develop a model simulating mastitis control in
      dairy herds and to investigate how sensitive the model is when varying the effect
      parameters according to the uncertainty. The model simulates 9 pathogen-specific
      mastitis types, each of which can be subclinical or clinical. The clinical cases
      can be 1 of 4 severities defined according to the effect of the mastitis case:
      mild, moderate, severe, and permanent effect. The risk factors include lactation
      stage, parity, yield level, previous diseases, season, and contagious spread of
      the infection from herd mates. Occurrence of mastitis is modeled to have direct
      effects on feed intake, body weight, milk yield, somatic cell count in the milk,
      subsequent mastitis cases within the cow and in herd mates, voluntary and
      involuntary culling, mortality, and milk withdrawal. Thirty-five scenarios were
      simulated to study model behavior and model sensitivity. The consequences per
      cow/yr of mastitis in the default simulated herd included 0.42 clinical mastitis
      occurrences, 0.56 subclinical mastitis occurrences, loss of 385-kg milk yield, a
      1.3% reduced feed intake, 61-kg milk withdrawal and 146 in reduced economic net
      return. Based on scenarios demonstrating model behavior and sensitivity analysis,
      the model appears to produce valid consequences of mastitis control strategies.
      Representation of the effect of subclinical mastitis and of variation in mastitis
      severity was concluded in this study to be important when modeling mastitis
      economics in a dairy herd. The model offers the opportunity to study the long
      term herd specific effects of a wide range of control strategies against
      mastitis.

PMID- 16291618
TI  - A partial budget model to estimate economic benefits of lactational treatment of
      subclinical Staphylococcus aureus mastitis.
AB  - Subclinical Staphylococcus aureus mastitis is rarely treated during lactation
      because it is widely believed to be uneconomical, although there are no economic
      studies that support this view. Partial budgeting was used to develop a
      deterministic simulation model to estimate the net cost or benefit of antibiotic
      treatment of subclinical S. aureus mastitis during lactation. Direct and indirect
      effects of treatment were taken into account, including prevention of clinical
      flare-ups and contagious transmission. Input variables were based on literature
      and on 2003-2004 prices in the Netherlands. When contagious transmission of S.
      aureus was likely (reproductive ratio R = 5.3), 3- and 8-d treatments resulted in
      an average net profit of 95.62 euros and 142.42 euros, respectively, compared
      with no treatment. When the probability of S. aureus transmission was low (R =
      0.32), the average economic benefit of 3- or 8-d treatment was -21.12 euros and 
      57.70 euros, respectively. On low-transmission farms, 3-d treatment was
      profitable when the appropriate cows were selected for treatment using known risk
      factors for cure. Sensitivity analysis showed that the 6 most influential input
      variables in the model were chance of bacteriological cure, R, probability of
      culling, retention pay-off, and cost of antibiotics and bacterial culture.
      Although the economic outcome of lactational treatment of subclinical S. aureus
      mastitis is highly herd-, cow-, and strain-dependent, treatment is economically
      justified in many situations.

PMID- 16291617
TI  - Effect of grazing and fat supplementation on production and reproduction of
      Holstein cows.
AB  - The objective of this trial was to investigate the effects of feeding a soybean
      oil refining by-product (SORB), made up mainly of sodium salts of long-chain
      fatty acids, on reproductive performance and productivity of 36 early lactation
      Holstein cows managed in a free-stall barn or on annual rye-ryegrass pasture. In
      this 2 x 2 factorial arrangement of treatments, cows consumed 0 or 0.5 kg/d of
      SORB as part of a total mixed ration for barn cows or as part of a grain
      supplement fed to cows on intensively, rotationally stocked pasture. Blood was
      sampled 3 times weekly and plasma was measured for progesterone to assess ovarian
      activity. Estrus activity was recorded using the HeatWatch estrus detection
      system. Although average 14-wk milk production (37.2 kg/d) was not different
      among treatments, barn cows had more persistent lactations than did grazing cows.
      Cows housed in the barn lost less body weight and returned to initial body weight
      sooner and had lower mean concentrations of plasma nonesterified fatty acids (464
      vs. 261 mEq/L) than those managed on pasture. The milk fat of cows on pasture
      contained greater proportions of conjugated linoleic acid and linolenic acid but
      a corresponding 0.22 percentage unit decrease in milk fat concentration (3.39 vs.
      3.16%). Cows managed on pasture had greater peak concentrations of plasma
      progesterone during the first estrous cycle. Cows managed on pasture and fed SORB
      had the greatest accumulation of plasma progesterone over the 14 wk of the study
      (SORB x housing interaction). These cows experienced the most mounts during their
      first estrus (9.3) and pregnancy rate was also greatest for this treatment
      (62.5%). Feeding SORB did not affect production of milk, fat, or protein. Loss of
      body condition was less in cows fed SORB. Ruminal fluid concentration of
      propionate increased and ruminal pH decreased in cows fed SORB. A lower
      proportion of fatty acids less than 18 carbons in length was found in the milk
      fat of cows fed SORB, thus indicating lower de novo synthesis of fatty acids.
      Higher proportions of C18:2n-6 and conjugated C18:2 were found in the milk fat of
      cows fed SORB. Based on concentrations of plasma progesterone, cows fed SORB
      experienced their first ovulation earlier (26.7 vs. 42.4 d postpartum) than did
      cows not supplemented with SORB. Neither housing system nor SORB supplementation
      influenced detection of first estrus (50.5 d) or the mean length of each estrus
      period (447 min).

PMID- 16291619
TI  - Distribution and carbohydrate structures of high molecular weight glycoproteins,
      MUC1 and MUCX, in bovine milk.
AB  - High molecular weight glycoproteins, MUC1 and MUCX, originating from bovine milk,
      were compared with regard to their distribution in milk fat and skim milk
      fractions and for presence of carbohydrate structures. Polymorphic MUC1, which
      migrated into 6% resolving SDS-PAGE gels, was found in both milk fat globule
      membrane and skim milk phases of bovine milk. In contrast, MUCX, appearing as a
      non-polymorphic single band in 3% polyacrylamide stacking gels, was present only
      in the skim milk fraction. Peptide-N-glycosidase F digestion studies indicated
      that MUC1 and MUCX possessed N-glycans with MUC1 containing more N-glycans than
      MUCX. Exoglycosidase digestion studies revealed the existence of abundant
      terminal sialic acid residues in both MUC1 and MUCX. Lectin-binding studies
      showed that MUCX likely possessed more complex carbohydrate structures than MUC1.
      The complex carbohydrate structures carried by both MUC1 and MUCX suggest that
      they may have potential to bind a wide spectrum of pathogenic microorganisms. If
      that proves to be the case in vivo, such structures could have a role in
      preventing or reducing some infectious diseases.

PMID- 16291620
TI  - Antioxidants to prevent bovine neutrophil-induced mammary epithelial cell damage.
AB  - Activated neutrophils are able to produce a large quantity of bactericidal
      molecules such as reactive oxygen species that have been associated with tissue
      damage in several inflammation models. The protective effects of antioxidants in
      a context of neutrophil-induced damage to mammary epithelial cells were first
      evaluated in vitro using a coculture model of activated bovine neutrophils and a
      bovine mammary epithelial cell line (MAC-T cells). Cell damage was determined by
      quantifying the release of lactate dehydrogenase by MAC-T cells in culture
      medium. Morphological observation of cells stained with acridine orange was used
      to visualize the extent of cell damage. When incubated with neutrophils activated
      by lipopolysaccharides and phorbol 12-myristate 13-acetate, MAC-T cells released
      large amounts of lactate dehydrogenase indicating significant cell damage. The
      addition of dimethylthiourea or bathocuproine disulfonic acid did not reduce the
      damage whereas catechin, deferoxamine or glutathione ethyl ester significantly
      reduced neutrophil-induced cytotoxicity in a dose-dependent manner. The effect of
      deferoxamine, an iron chelator, on the growth of Escherichia coli and the ability
      of bovine neutrophils to phagocytose these bacteria were then assessed in vitro.
      Our data showed that deferoxamine did not interfere with the phagocytic activity
      of neutrophils but inhibited growth of the bacteria. Overall, our results suggest
      that antioxidants may be effective tools for protecting mammary tissue against
      neutrophil-induced oxidative stress during bovine mastitis.

PMID- 16291622
TI  - Short communication: Conception rates following detection of estrus and timed AI
      in dairy cows synchronized using GnRH and PGF2alpha.
AB  - The objective of this study was to compare conception rates of cows exhibiting
      spontaneous estrus and receiving artificial insemination (AI) before completion
      of a timed AI protocol with cows that did not display estrus spontaneously, but
      were inseminated after 1 of 3 GnRH-PGF2alpha protocols. Cows (n = 432) in 2 herds
      were administered GnRH on d -7 and were tail-chalked daily. Cows detected in
      estrus before d 0 were inseminated immediately. Cows not detected in estrus by d
      0 were administered PGF2alpha and were tail-chalked daily until 48 h after
      PGF2alpha. Cows detected in estrus from d -7 to 48 h after PGF2alpha were
      inseminated and designated as treatment A (n = 46). Cows not detected in estrus
      and not inseminated by 48 h after PGF2alpha were assigned randomly to receive
      either GnRH 48 h after PGF2alpha and timed AI 16 h later (treatment B; n = 132),
      or GnRH and timed AI 64 h after PGF2alpha (treatment C; n = 127), or timed AI 64
      h after PGF2alpha (treatment D; n = 127). Pregnancy was diagnosed 38 to 45 d
      after AI by palpation per rectum of uterine contents. Nearly 11% of all cattle
      exhibited spontaneous estrus and received immediate AI. Herd did not influence
      the percentage of cows detected in estrus and inseminated. Conception rates did
      not differ among treatments. Conception rates differed between herds, but no
      interaction of herd x treatment was detected. No differences were detected
      between herds for days in milk, milk production, AI service number, or parity.

PMID- 16291621
TI  - Influence of bedding material on ammonia emissions from cattle excreta.
AB  - Dairy cattle barns are a major source of NH3 emissions to the atmosphere.
      Previous studies have shown that the bedding material used in the barn can
      influence the magnitude of NH3 emissions, but little is known about which bedding
      characteristics are important in this respect. The aims of this study were to
      assess, at a laboratory scale, the relative importance of the chemical [pH,
      cation exchange capacity (CEC), C:N] and physical (urine absorbance capacity,
      bulk density) characteristics of 5 bedding materials (chopped wheat straw, sand,
      pine shavings, chopped newspaper, chopped corn stalks, and recycled manure
      solids) on NH3 emissions from dairy cattle urine. Recycled manure solids were the
      most absorbent of the bedding types (4.2 g of urine/g of bedding), and sand was
      the least (0.3 g of urine/g of bedding). When beddings were soaked in urine to
      their absorbance capacities, NH3 emissions over 48 h (expressed as a proportion
      of the urine N absorbed) were not significantly different among bedding types,
      despite differences in initial bedding pH, CEC, and C:N. When equal volumes of
      urine were applied to equal depths of dry bedding, NH3 emissions over 48 h were
      significantly less from sand and pine shavings (23 and 42% of applied urine N,
      respectively) than from chopped newspaper, chopped corn stalks, and recycled
      manure solids (62, 68, and 65% of applied urine N, respectively), whereas
      emissions from chopped wheat straw (55% applied urine N) only differed
      significantly from that from sand. Differences in the chemical characteristics of
      the beddings did not explain differences in emission; NH3 emissions increased
      linearly with CEC contrary to expectations, and there was no significant
      relationship with initial bedding pH. The physical characteristics of bedding
      materials were of more importance, as NH3 emissions increased linearly with
      absorbance capacity and decreased as the bulk density of the packed beddings
      increased.

PMID- 16291623
TI  - Comparison of bacteria populations in clean and recycled sand used for bedding in
      dairy facilities.
AB  - Bedding samples were collected twice from commercial dairy free-stall facilities
      that used recycled sand and clean sand in both the summer and winter. Collection
      began on the day sand was taken from the pile (d 0) and placed in the free
      stalls, and continued for 5 to 7 additional days. The number of colonies per gram
      of bedding of gram-negative bacteria, coliforms, Streptococcus spp., and
      Klebsiella spp. were estimated for each sand sample as well as amounts of dry and
      organic matter. Clean sand (CS) and recycled sand (RS) had the same bacterial
      counts when compared at any sampling time. The mean counts of bacterial
      populations did vary over the course of the study in both CS and RS. There was a
      significant increase in bacterial counts from d 0 to d 1 for gram-negative
      bacteria, coliforms, and Streptococcus spp. in both winter and summer. Counts of
      gram-negative bacteria, coliforms, Klebsiella spp., and Streptococcus spp. did
      not differ from d 1 to 7 in the winter. Total counts of gram-negative bacteria
      did not differ from d 1 to 7 in the summer. On d 1 in the summer, coliform counts
      were lower than at d 5 to 7, and Klebsiella spp. counts were lower than on d 3 to
      7. Streptococcus spp. counts were high on d 1 and were constant through d 7 in
      both winter and summer trials. The number of coliform and Klebsiella spp. in both
      CS and RS was below the threshold thought to cause mastitis during the sampling
      times. The number of Streptococcus spp. was high in both CS and RS during the
      sampling periods. Other management factors need to be identified to decrease the
      number of Streptococcus spp. in bedding. Recycled sand had a higher organic
      matter and lower dry matter compared with CS in winter and summer. The results
      for this study were obtained from multiple herd comparisons, and herd was a
      significant effect suggesting that different management systems influence the
      number and types of bacteria in both CS and RS.

PMID- 16291624
TI  - Exposure to a physiologically relevant elevated temperature hastens in vitro
      maturation in bovine oocytes.
AB  - The objective of this study was to evaluate nuclear (progression to metaphase II)
      and cytoplasmic (translocation of cortical granules to the oolemma) maturation in
      control (38.5 degrees C) and heat-stressed (41.0 degrees C) oocytes. Hoechst
      staining indicated that a similar proportion of control and heat-stressed oocytes
      progressed to meta-phase II. More heat-stressed oocytes had type III cortical
      granule distribution suggesting that heat stress accelerated cytoplasmic
      maturation. The kinetics of nuclear maturation was examined in a second
      experiment in which a higher proportion of heat-stressed oocytes progressed to
      metaphase I by 8 h and arrested at meta-phase II at 16 and 18 h after placement
      into maturation medium. However, differences related to maturation temperature
      were no longer apparent by 21 h. Heat-induced alterations in kinetics of nuclear
      and cytoplasmic maturation prompted a third experiment to evaluate if earlier
      insemination of heat-stressed oocytes ameliorates heat-induced reductions in
      development. A significant temperature x insemination time interaction was noted
      when evaluating blastocyst development. Blastocyst development was reduced when
      heat-stressed oocytes were inseminated with sperm 24 h after placement into
      maturation medium compared with controls. In contrast, blastocyst development was
      similar to controls when heat-stressed oocytes were inseminated at 19 h. Based on
      this interaction, earlier insemination in vitro prevented heat-induced reductions
      in oocyte development. Collectively, these studies suggest a cumulative effect of
      heat stress to hasten in vitro maturation in bovine oocytes.

PMID- 16291625
TI  - Dilution rate and pH effects on the conversion of oleic acid to trans C18:1
      positional isomers in continuous culture.
AB  - In a previous in vitro study, mixed ruminal microorganisms converted oleic acid
      to a variety of trans monenes when grown in batch cultures under constant
      environmental conditions. To determine whether a similar conversion occurs under
      environmental conditions more typical of the rumen, conversion of 13C-labeled
      oleic acid to biohydrogenation intermediates was determined in ruminal
      microorganisms grown in continuous culture at two pH (5.5 and 6.5) and liquid
      dilution rates (0.05 and 0.10/h) arranged factorially. After each morning feeding
      of the dual-flow continuous cultures, 250 mg of oleic acid in 5 mL of ethanol
      were injected into each culture. On d 10, 250 mg of oleic-1-(13C) replaced the
      unlabelled oleic acid in ethanol. Trans fatty acids were isolated from culture
      samples by solid phase extraction, and 13C enrichment and identity of double bond
      position was determined by gas chromatography-mass spectroscopy. At pH 6.5 and
      0.10/h dilution rate, 13C enrichment was detected in all trans-C18:1 isomers
      having double bond positions from C6 through C16 in the acyl chain. However, when
      pH or dilution rate in fermentors was lowered, no 13C enrichment was detected in
      any trans isomer with a double bond position beyond C10. Enrichment in stearic
      acid increased by reducing culture pH from 6.5 to 5.5, but decreased when
      dilution rate dropped from 0.10 to 0.05/h. The stearic acid carbons that
      originated from oleic acid biohydrogenation increased from 30 to 72% when pH
      dropped from 6.5 to 5.5. The 13C enrichment of trans-10 was reduced under low pH
      and dilution rate conditions. The results of this study confirm that ruminal
      microorganisms are capable of converting oleic acid to a wide variety of trans
      C18:1 positional isomers when ruminal conditions are favorable (such as the pH
      6.5 and 0.10/h dilution rate treatment). However, at low pH and dilution rate,
      the conversion of oleic acid to trans-C18:1 still occurs, but positional isomers
      produced are restricted to double bond positions from C6 to C10. Low pH
      conditions also increased the conversion of oleic acid to stearic acid.

PMID- 16291626
TI  - Processing whole cottonseed moderates fatty acid metabolism and improves
      performance by dairy cows.
AB  - Pelleting cottonseed (CS) improves handling characteristics. Our objectives were
      to determine whether increasing the particle size of the CS pellet or dilution of
      a smaller pellet with delinted CS would limit the rate of CS oil release to
      optimize digestibility of fatty acids (FA) and fiber while maintaining milk fat
      production. In a 5 x 5 Latin square design with 3-wk periods, 5 rumen-cannulated
      cows were fed 1) control with CS hulls (CSH) and CS meal plus tallow and Ca soaps
      of FA, 2) whole CS (WCS), 3) small CS pellets (SP; 0.44-cm die diameter), 4)
      larger CS pellets (LP; 0.52-cm die diameter), or 5) a blend of 1/2 SP plus 1/2
      partially delinted CS (SPD). Diets contained 39.6% concentrate, 14.4% CS, and 46%
      forage (40:60, alfalfa hay:corn silage) on a DM basis and were balanced to have
      similar concentrations of CS protein, CS fiber, and total fat. In a production
      trial, dietary treatments were 1) WCS control, 2) LP, 3) SPD, and 4) SPD fed at
      90%. Sixty cows averaging 105 d in milk were fed the WCS diet for 2 wk and then
      assigned to one of the 4 diets for 12 wk. Total tract digestibility of NDF was
      unaffected, but N digestibility was lower for SPD than for other treatments.
      Fatty acid digestibility was higher for SP and LP (82.6 and 82.3%) than for CSH
      or SPD treatments (78.8 and 75.3%), and WCS was intermediate (81.1%). The trans
      11 C18:1 from cows fed SP and LP (6.58 and 6.24% of total milk FA) was greater
      than that from cows fed CSH, WCS, and SPD (3.23, 3.79, and 3.97%). The trans-10
      C18:1 in milk fat from SP and LP (0.508 and 0.511%) was higher than that in WCS
      and SPD diets (0.316 and 0.295%); CSH was intermediate (0.429%). Using passage
      rates estimated from the NRC, disappearance of total FA in situ was estimated to
      be 17.7, 44.2, 46.6, and 35.0% for WCS, SP, LP, and SPD, respectively. In the
      production trial, a diet x week interaction was explained by a trend for
      progressively greater milk production for SPD and SPD90 than for WCS or LP. Milk
      fat was lower for LP (2.74%) and SPD90 (2.85%) than for WCS or SPD (3.07 and
      3.08%). The fat yield was lower for LP than for SPD (1.09 and 1.30 kg/d); WCS and
      SPD90 were intermediate (1.23 and 1.21 kg/d). Although having a lower FA
      digestibility, SPD appeared to minimize negative effects of free oil from SP in
      the rumen, explaining higher DMI and milk production compared with WCS or LP.

PMID- 16291627
TI  - Long-day photoperiod that enhances puberty does not limit body growth in Holstein
      heifers.
AB  - Previous research has demonstrated that extended photoperiod accelerates
      pubescence in dairy heifers thereby limiting time for mammary development, which
      could be detrimental to future milk yield. We hypothesized that the potential
      negative effects of rapid growth and puberty through long-day photoperiod (LDPP)
      exposure could be overcome with a greater supply of metabolizable protein in
      dairy heifers fed rumen-undegradable protein (RUP). In an initial slaughter
      study, we compared deuterium oxide (D2O) and direct chemical analysis to assess
      body composition at 5 and 7 mo of age in heifers (n = 20) exposed to LDPP or
      short-day photoperiod (SDPP). Before slaughter, D2O dilution was used to estimate
      body composition and results were compared with actual values determined by
      direct chemical analysis of body tissue. In 5-mo-old heifers, the correlations
      between estimates of body protein, water, and mineral contents as determined by
      D2O dilution and direct chemical analysis of body tissue were 0.86, 0.85, and
      0.76, respectively; however, fat content values were not correlated (r = -0.068).
      In 7-mo-old heifers, we were unable to accurately estimate body composition using
      the D2O dilution method. A second study was conducted to determine if LDPP, which
      has previously been shown to hasten puberty, could be combined with RUP to
      promote lean growth without limiting body stature in prepubertal heifers. Thirty
      two weaned heifers (86 +/- 2 d old; 106.2 +/- 17.3 kg of body weight) were
      assigned to LDPP or SDPP and RUP or control diet in a 2 x 2 factorial arrangement
      until the onset of puberty. Relative to SDPP, LDPP increased prolactin secretion
      and promoted lean growth. Exposure to LDPP also enhanced body weight, withers
      height, and heart girth. Furthermore, RUP supplementation increased withers
      height and heart girth. There was a significant interaction between LDPP and RUP
      for hip height. Moreover, LDPP hastened the onset of puberty. In summary, D2O was
      a feasible method to estimate lean composition in heifers at younger ages;
      however, it failed to accurately estimate body composition in heifers around
      puberty. Long-day photoperiod hastened puberty and accelerated lean growth
      without limiting skeletal growth in dairy heifers.

PMID- 16291628
TI  - Effect of selenium source on selenium status, neutrophil function, and response
      to intramammary endotoxin challenge of dairy cows.
AB  - The effects of feeding dry and early lactation dairy cows diets with selenate or
      selenized yeast (Se-yeast) on concentrations of Se in serum, milk, and newborn
      calves, neutrophil function, and inflammatory response were determined. At 60 d
      before anticipated calving until approximately 30 d in milk (DIM), cows were fed
      diets that contained 0.3 mg of supplemental Se/kg of DM from sodium selenate or
      Se-yeast. Diets also contained 0.2% supplemental S (as sulfate) because it has
      been shown to reduce absorption of Se by dairy cows. The concentration of Se in
      serum at calving and 28 DIM was about 1.4 times greater for cows fed Se-yeast
      than for those fed selenate. Serum concentrations decreased 45 and 23% from dry
      off to calving for cows fed selenate or Se-yeast, respectively. Selenium
      concentrations in serum from newborn calves were also about 1.4 times greater
      when the dams were fed Se-yeast. Concentrations of Se in colostrum and milk were
      about 1.8 times greater when cows were fed Se-yeast. Blood neutrophils were
      isolated from cows at 28 DIM and were used in an in vitro kill assay. Selenium
      treatment did not affect bacterial kill or the percentage of neutrophils that
      phagocytized bacteria. At approximately 28 DIM, one quarter from each cow was
      infused with a solution containing endotoxin. Peak body temperature (40.7 degrees
      C) occurred 6 h postinfusion, and peak somatic cell count (6.5 log10/mL) occurred
      at 12 h postinfusion. Neither measure was influenced by Se treatment.

PMID- 16291629
TI  - Effects of pre- and postfresh transition diets varying in dietary energy density
      on metabolic status of periparturient dairy cows.
AB  - Effects of dietary energy density during late gestation and early lactation on
      metabolic status of periparturient cows were studied. Four weeks before expected
      calving, animals were fed a low (DL; 1.58 Mcal of NEL/kg) or high energy density
      diet (DH; 1.70 Mcal of NEL/kg). After calving, half of the cows from each
      prepartum treatment were assigned to a low (L; 1.57 Mcal of NEL/kg) or high
      energy density diet (H; 1.63 Mcal of NEL/kg) until d 20 postpartum. After d 20,
      all animals were fed H until d 70. Animals fed DH had a more positive energy
      balance during the prepartum period. Animals fed DH had higher plasma
      concentrations of glucose and insulin and lower concentrations of plasma
      nonesterified fatty acid (NEFA) on d -7 relative to calving compared with animals
      fed DL. No differences in blood concentrations of metabolites, insulin and liver
      triglycerides (TG) content were observed on d 1. Liver TG content at d 1 and 21
      were more related to magnitude of change in energy intake prepartum than to
      energy intake in the last week of gestation. Cows fed H had higher concentrations
      of plasma glucose and insulin, but similar plasma NEFA during the postpartum
      period compared with cows fed L. Plasma concentrations of beta-hydroxybutyrate
      (BHBA) and liver TG content on d 21 were 46 and 30% lower, respectively, for cows
      fed H compared with cows fed L. Interactions between prepartum and postpartum
      treatments indicated that negative effects of delaying higher concentrate feeding
      until d 21 postpartum can be partially offset by increasing concentrate in the
      diet before calving. Cows fed L had a higher increase in white line hemorrhage
      scores between prepartum and 10 wk postpartum compared with cows fed H. Energy
      density of prepartum diets had a minor influence on metabolic status of cows
      postpartum. A more favorable metabolic profile occurs when increasing the
      concentrate content of the diet immediately postpartum compared with delaying the
      increase until d 21 postpartum.

PMID- 16291630
TI  - Effects of dietary cation-anion difference on intake, milk yield, and blood
      components of the early lactation cow.
AB  - Early lactation Holsteins cows (15 primiparous and 18 multiparous) were offered
      rations with dietary cation-anion difference, calculated as mEq (Na + K - Cl -
      S)/100 g of feed dry matter (DCAD:S), of 20, 35, or 50 mEq from d 0 (calving) to
      42 d postpartum (August 20, 2000 to January 9, 2001) to determine the effects of
      increasing DCAD:S on dry matter intake (DMI), milk yield, and blood metabolites.
      For DCAD:S of 20, 35, and 50, DMI was 3.30, 3.38, 2.96 kg/100 kg of body weight
      (BW); milk yield was 25.5, 24.2, and 22.4 kg/d, respectively. No differences were
      observed for concentration or yield of milk fat or milk protein. Serum Ca, P, Mg,
      Na, K, Cl, cation-anion difference, insulin, and glucose did not differ with
      DCAD. Serum HCO3- was 26.07, 25.88, and 27.64 mEq/L for 20, 35, and 50 DCAD:S.
      Serum Ca, Mg, Na, and K concentrations were greater for primiparous cows (9.52
      mg/dL, 2.35 mg/dL, 140.03 mEq/L, 4.66 mEq/L, respectively) than for multiparous
      cows (9.27 mg/dL, 2.12 mg/dL, 137.63 mEq/L, 4.46 mEq/ L, respectively). A DCAD:S
      between 23 and 33 mEq/100 g of dry matter (DM) appears to be adequate during cool
      weather for the milk yield that occurred in the present study based on DMI
      (kg/100 kg of BW), whereas DCAD:S of 50 mEq/100 g of DM may be excessive and
      could be too alkaline or unpalatable, resulting in decreased DMI (kg/100 kg of
      BW).

PMID- 16291631
TI  - Effect of garlic oil and four of its compounds on rumen microbial fermentation.
AB  - Different concentrations (3, 30, 300, and 3000 mg/L of culture fluid) of garlic
      oil (GAR), diallyl sulfide (DAS), diallyl disulfide (DAD), allicin (ALL), and
      allyl mercaptan (ALM) were incubated for 24 h in diluted ruminal fluid with a
      50:50 forage:concentrate diet (17.7% crude protein; 30.7% neutral detergent
      fiber) to evaluate their effects on rumen microbial fermentation. Garlic oil (30
      and 300 mg/L), DAD (30 and 300 mg/L), and ALM (300 mg/L) resulted in lower molar
      proportion of acetate and higher proportions of propionate and butyrate. In
      contrast, at 300 mg/L, DAS only increased the proportion of butyrate, and ALL had
      no effects on volatile fatty acid proportions. In a dual-flow continuous culture
      of rumen fluid fed the same 50:50 forage:concentrate diet, addition of GAR (312
      mg/L), DAD (31.2 and 312 mg/L), and ALM (31.2 and 312 mg/L) resulted in similar
      changes to those observed in batch culture, with the exception of the lack of
      effect of DAD on the proportion of propionate. In a third in vitro study, the
      potential of GAR (300 mg/L), DAD (300 mg/L), and ALM (300 mg/L) to decrease
      methane production was evaluated. Treatments GAR, DAD, and ALM resulted in a
      decrease in methane production of 73.6, 68.5, and 19.5%, respectively, compared
      with the control. These results confirm the ability of GAR, DAD, and ALM to
      decrease methane production, which may help to improve the efficiency of energy
      use in the rumen.

PMID- 16291632
TI  - Effects of dietary alpha-amylase on metabolism and performance of transition
      dairy cows.
AB  - Twenty-four multiparous Holstein cows [body weight, 759 kg (SD = 30 kg); body
      condition score, 3.2 (SD = 0.13)] were used in a randomized complete block design
      to determine the effect of feeding alpha-amylase during the transition period on
      rumen fermentation, key metabolic indicators, and lactation performance. Cows
      were assigned to either a control diet or the control diet supplemented with
      alpha-amylase (662 fungal amylase units per gram, AMA) at 0.1% of diet dry matter
      (DM). Experimental diets were fed from 21 d before expected calving through 21 d
      in milk. From 22 to 70 d in milk, all cows were fed a similar lactation cow diet.
      Average pre- and postpartum DM intakes were 12.4 and 17.8 kg/d, respectively, and
      did not differ between treatments; however, DM intakes during the last week
      prepartum decreased to a greater degree in AMA than control cows compared with wk
      -2. Supplementing diets with alpha-amylase tended to increase proportions of
      ruminal butyrate prepartum but not postpartum. Treatment differences were not
      detected for concentrations of insulin in plasma and lipid and glycogen in liver
      tissue. Prepartum, concentrations of beta-hydroxybutyrate and nonesterified fatty
      acids were increased in cows fed AMA compared with the control diet. Postpartum,
      concentrations of glucose in plasma tended to be increased by feeding AMA.
      Increased plasma beta-hydroxybutyrate and nonesterified fatty acids pre- but not
      postpartum and a tendency for increased plasma glucose postpartum demonstrate
      shifting reliance from lipid- to carbohydrate-based metabolism postpartum in cows
      fed alpha-amylase.

PMID- 16291633
TI  - Chemical and physical characteristics of corn silages and their effects on in
      vitro disappearance.
AB  - Estimating the available energy in corn silage provides a unique challenge
      because the silage contains variable proportions of grain and stover, each of
      which can differ in availability due to chemical composition and physical form.
      The objectives of this study were to investigate relationships among chemical
      components and their relationships with in vitro disappearance of ground and
      unground dried silages, and to quantify minimally fragmented starch in corn
      silage and investigate its impact and that of mean particle size (MPS) on in
      vitro disappearance of unground silages. Thirty-two corn silages were selected to
      provide diversity in dry matter, protein, fiber, and MPS. Detergent fibers were
      highly correlated with each other and with nonfiber carbohydrates, and were used
      to develop prediction equations between these constituents. Sieves with apertures
      > or =4.75 mm were used to isolate intact kernels and large kernel fragments,
      which were collected and analyzed to measure minimally fragmented starch
      (Starch>4.75). Dividing Starch>4.75 by total starch defined the proportion of
      minimally fragmented starch (Starch>4.75/Total), which ranged from 9 to 100% with
      a mean of 52%. Starch>4.75/Total was positively correlated with MPS (r = 0.46).
      The inverse of Starch>4.75/Total is an index of kernel fragmentation. Silages
      were prepared as whole material or ground to pass through a 4- or 1-mm screen of
      a cutter mill. In vitro dry matter disappearance (IVDMD) was greater for ground
      than for whole samples (71.7 and 61.2%, respectively). Increased IVDMD for ground
      samples was attributed to greater in vitro neutral detergent fiber (NDF) and
      neutral detergent solubles (NDS) disappearances. The IVDMD of ground samples was
      related to NDF and acid detergent lignin (R2 = 0.80). The IVDMD of whole corn
      silage was related to acid detergent lignin, Starch>4.75, MPS, and dry matter.
      When IVDMD was partitioned into in vitro digestible NDS (IVdNDS) and in vitro
      digestible NDF, the IVdNDS of whole was not uniform or completely fermented. The
      difference in IVdNDS between ground and whole was related to Starch>4.75/Total.
      In conclusion, the proportion of minimally fragmented starch provides a corn
      silage fragmentation index that is related to the in vitro digestion of whole
      silages that, if validated by in vivo trials, may be a useful quantitative
      substitute for the qualitative processing adjustment factor that is used
      currently in summative equations for estimating the total digestible nutrients of
      corn silages.

PMID- 16291634
TI  - Cumulative discounted expressions of sire genotypes for the complex vertebral
      malformation and beta-casein loci in commercial dairy herds.
AB  - Based on discounted gene-flow principles, a set of recursive equations was
      developed to quantify the value of using sires with a specific genotype for an
      identified gene in a commercial dairy herd. Two examples were used to demonstrate
      the usefulness of the method. The first example deals with the implications of
      using sires that are known carriers of the lethal recessive genetic defect,
      complex vertebral malformation (CVM). The second example examines the value of
      using sires homozygous for the A2 allele of beta-casein. Results are presented in
      terms of cumulative discounted expressions. These are then multiplied by the
      economic values of specific genotypes to determine the cost or benefit of using
      these sires. In general, the degree of mortality and the required price reduction
      for carrier sires increased as the proportion of carrier sires used, the duration
      of sire use, and the initial frequency in the cow herd increased. A semen
      discount of 3.10 pound sterling per CVM straw used would be required to offset
      the expected mortality when 20% of CVM carrier sires are used for 3 yr when 5% of
      cows are carriers. The cumulative discounted expressions' of using sires
      homozygous for the A2 allele of beta-casein also increased when the proportion
      and duration of carrier sire use and the initial frequency of the A2 allele
      increased. Assuming an A2A2 cow is worth 160 pound sterling more than a non-A2A2
      cow, the expected benefit of using A2A2 sires in a 100-cow herd for 5 yr would be
      57 pound sterling,120 for a 20-yr planning horizon. The results of this study
      demonstrate how the starting gene frequency in the herd, and the proportion and
      duration of use of sires of particular genotypes are critical to the economic
      implications of using single genes in commercial dairy farms.

PMID- 16291635
TI  - Milk urea nitrogen concentration: heritability and genetic correlations with
      reproductive performance and disease.
AB  - The objectives of this study were to estimate the heritability of milk urea
      nitrogen (MUN) concentration and describe the genetic relationship between MUN
      and reproductive performance and between MUN and diseases in Holsteins. Dairy
      Records Management Systems (Raleigh, NC) provided lactation data. The Danish
      Agricultural Advisory Center provided breeding value estimates for diseases.
      Infrared (IR) and wet chemistry (WC) data were analyzed separately.
      Heritabilities and genetic correlations for 2 different measures of MUN and
      reproductive performance were estimated with an animal model using ASREML.
      Heritabilities for MUN were estimated using all lactations combined (lactations 1
      through 5) and separately for first lactation and second lactation. Genetic
      correlations with reproduction and health were estimated separately for parities
      1 and 2. Herd-test-day or herd-year-season along with age at calving and days in
      milk were included as fixed effects in all models. Heritability estimates for all
      lactations combined were 0.15 for WC MUN and 0.22 for IR MUN. Genetic
      correlations between WC MUN and 2 measures of reproductive performance, days to
      first service, and first service conception were not different from zero. In
      contrast, the genetic correlation between WC MUN and days open of 0.21 in first
      lactation and 0.41 in second lactation indicated that higher WC MUN values were
      associated with increased days open. Correlations among estimated breeding values
      for MUN and estimated breeding values for Danish diseases identified no
      significant relationships. Although the results of this study indicate that
      heritable variation for MUN exists, the inability to identify significant genetic
      relationships with several measures of disease or reproductive performance
      appears to limit the value of MUN in selection for disease resistance and
      improved reproduction.

PMID- 16291636
TI  - Ecology of Escherichia coli O157:H7 in commercial dairies in southern Alberta.
AB  - Shedding of Escherichia coli O157:H7 was monitored monthly over a 1-yr period by
      collecting pooled fecal pats (FECAL) and manila ropes orally accessed for 4 h
      (ROPE) from multiple pens of cattle in 5 commercial dairies in southern Alberta,
      Canada. Using immunomagnetic separation, E. coli O157:H7 was isolated from cows
      on 4 of the dairies and from 13.5% of FECAL and 1.1% of ROPE samples. Pulsed
      field gel electrophoresis of XbaI- and SpeI-digested bacterial DNA of the 65
      isolates produced 23 unique restriction endonuclease digestion patterns, although
      92% of the isolates belonged to 3 restriction endonuclease digestion pattern
      clusters sharing a minimum 90% homology. Collection of positive isolates was 15
      times more likely from June through September. Across dairies, peak somatic cell
      count occurred in July, August, September, and November. The likelihood of
      positive isolates was 2.6 times higher in calves and heifers compared with mature
      cows. This study indicates that ROPE would be of little value for the detection
      of E. coli O157:H7 in dairy herds unless oral contact with ROPE could be
      increased in mature animals. Additionally, mitigation strategies for E. coli
      O157:H7 should be targeted to the months of July, August, and September and
      toward immature animals for maximum impact. All farms displayed unique
      combinations of seasonality of shedding and diversity of E. coli O157:H7
      subtypes. The fact that seasonal prevalence of E. coli O157:H7 largely coincided
      with peak somatic cell count within climatically controlled dairy barns suggests
      that similar environmental factors may be enhancing fecal shedding E. coli
      O157:H7 and the incidence of mastitis.

PMID- 16291637
TI  - Thyroid dysgenesis: multigenic or epigenetic ... or both?

PMID- 16291638
TI  - Too many follistatins: racing inside and getting out of the cell.

PMID- 16291640
TI  - Doctors' strategies in prescribing drugs: the case of mood-modifying medicines.
AB  - BACKGROUND: Little is known about doctors' decision-making processes in
      prescribing antidepressants and how this is handled. OBJECTIVE: To describe and
      understand doctors' strategies in prescribing mood-modifying drugs, especially
      when confronted with challenging patients or situations. METHODS: Face-to-face
      interviews were conducted with GPs in Gottingen and Hannover, two areas in the
      north of Germany. GPs were enrolled until a sufficient variation ('saturation')
      had been reached (n = 19). Interviews were audiotaped and then transcribed
      verbatim. To analyse the GPs' concepts and strategies in prescribing
      antidepressants, the interviews were structured according to themes and recurrent
      items extracted by theoretical coding. RESULTS: We identified four main
      strategies used by GPs in the pharmacological management of depressive patients:
      marketing additional beneficial drug effects, addressing the patients as experts,
      somatic attribution of the disease and referral to a specialist. CONCLUSIONS: To
      support their prescription, GPs use a variety of strategies to motivate both
      patients to take a certain drug and themselves to deal with difficult patients or
      situations in their management of depression.

PMID- 16291641
TI  - In vivo regeneration of small-diameter (2 mm) arteries using a polymer scaffold.
AB  - The difficulty of obtaining significant long-term patency and good wall
      mechanical strength in vivo has been a significant obstacle in achieving small
      diameter vascular prostheses. The aim of the present study was to develop a
      prosthetic graft that could perform as a small-diameter vascular conduit. Tubular
      structures of hyaluronan (HYAFF-11 tubules, 2 mm diameter, 1 cm length) were
      grafted in the abdominal aorta of 30 rats as temporary absorbable guides to
      promote regeneration of vascular structures. Performance was assessed by
      histology, immunohistochemistry, and ultra-structural analysis. These experiments
      resulted in three novel findings: 1) complete endothelialization of the tube's
      luminal surface occurred; 2) sequential regeneration of vascular components led
      to complete vascular wall regeneration 15 days after surgery; and 3) the
      biomaterial used created the ideal environment for the delicate regeneration
      process during the critical initial phases, yet its biodegradability allowed for
      complete degradation of the construct four months after implantation, at which
      time, a new artery remained to connect the artery stumps. This study assesses the
      feasibility to create a completely biodegradable vascular regeneration guide in
      vivo, able to sequentially orchestrate vascular regeneration events needed for
      very small artery reconstruction.

PMID- 16291642
TI  - Differential gene expression profiling of short and long term denervated muscle.
AB  - Skeletal muscle function and viability are dependent upon intact innervation.
      Peripheral nerve injury and muscle denervation cause muscle atrophy. Time to re
      innervation is one of the most important determinants of functional outcome.
      While short-term denervation can result in nearly fully reversible changes in
      muscle mass, prolonged denervation leads to irreversible muscle impairment from
      profound atrophy, myocyte death and fibrosis. We performed transcriptional
      profiling to identify genes that were altered in expression in short-term (1
      month) and long-term (3 month) denervated muscle and validated the microarray
      data by RT-PCR and Western blotting. Genes controlling cell death, metabolism,
      proteolysis, stress responses and protein synthesis/translation were altered in
      expression in the denervated muscle. A differential pattern of expression of
      genes encoding cell cycle regulators and extracellular matrix components was
      identified that correlated with the development of irreversible post-denervation
      changes. Genes encoding mediators of protein degradation were differentially
      expressed between 1 and 3 month denervated muscle suggesting different signaling
      networks are recruited over time to induce and maintain muscle atrophy.
      Understanding of the timing and type of pathological processes that are triggered
      by denervation may allow the design of interventions that delay or protect muscle
      from loss of nerve function.

PMID- 16291643
TI  - Bacterial outer membrane vesicles and the host-pathogen interaction.
AB  - Extracellular secretion of products is the major mechanism by which Gram-negative
      pathogens communicate with and intoxicate host cells. Vesicles released from the
      envelope of growing bacteria serve as secretory vehicles for proteins and lipids
      of Gram-negative bacteria. Vesicle production occurs in infected tissues and is
      influenced by environmental factors. Vesicles play roles in establishing a
      colonization niche, carrying and transmitting virulence factors into host cells,
      and modulating host defense and response. Vesicle-mediated toxin delivery is a
      potent virulence mechanism exhibited by diverse Gram-negative pathogens. The
      biochemical and functional properties of pathogen-derived vesicles reveal their
      potential to critically impact disease.

PMID- 16291644
TI  - Regulation of an intergenic transcript controls adjacent gene transcription in
      Saccharomyces cerevisiae.
AB  - Recent studies have revealed that transcription of noncoding, intergenic DNA is
      abundant among eukaryotes. However, the functions of this transcription are
      poorly understood. We have previously shown that in Saccharomyces cerevisiae,
      expression of an intergenic transcript, SRG1, represses the transcription of the
      adjacent gene, SER3, by transcription interference. We now show that SRG1
      transcription is regulated by serine, thereby conferring regulation of SER3, a
      serine biosynthetic gene. This regulation requires Cha4, a serine-dependent
      activator that binds to the SRG1 promoter and is required for SRG1 induction in
      the presence of serine. Furthermore, two coactivator complexes, SAGA and Swi/Snf,
      are also directly required for activation of SRG1 and transcription interference
      of SER3. Taken together, our results elucidate a physiological role for
      intergenic transcription in the regulation of SER3. Moreover, our results
      demonstrate a mechanism by which intergenic transcription allows activators to
      act indirectly as repressors.

PMID- 16291645
TI  - Homologous recombination and nonhomologous end-joining repair pathways regulate
      fragile site stability.
AB  - Common fragile sites are specific loci that form gaps and constrictions on
      metaphase chromosomes exposed to replication stress, which slows DNA replication.
      These sites have a role in chromosomal rearrangements in tumors; however, the
      molecular mechanism of their expression is unclear. Here we show that replication
      stress leads to focus formation of Rad51 and phosphorylated DNA-PKcs, key
      components of the homologous recombination (HR) and nonhomologous end-joining
      (NHEJ), double-strand break (DSB) repair pathways, respectively. Down-regulation
      of Rad51, DNA-PKcs, or Ligase IV, an additional component of the NHEJ repair
      pathway, leads to a significant increase in fragile site expression under
      replication stress. Replication stress also results in focus formation of the DSB
      markers, MDC1 and gammaH2AX. These foci colocalized with those of Rad51 and
      phospho-DNA-PKcs. Furthermore, gammaH2AX and phospho-DNA-PKcs foci were localized
      at expressed fragile sites on metaphase chromosomes. These findings suggest that
      DSBs are formed at common fragile sites as a result of replication perturbation.
      The repair of these breaks by both HR and NHEJ pathways is essential for
      chromosomal stability at these sites.

PMID- 16291646
TI  - HTP-1-dependent constraints coordinate homolog pairing and synapsis and promote
      chiasma formation during C. elegans meiosis.
AB  - Synaptonemal complex (SC) assembly must occur between correctly paired homologous
      chromosomes to promote formation of chiasmata. Here, we identify the
      Caenorhabditis elegans HORMA-domain protein HTP-1 as a key player in coordinating
      establishment of homolog pairing and synapsis in C. elegans and provide evidence
      that checkpoint-like mechanisms couple these early meiotic prophase events. htp-1
      mutants are defective in the establishment of pairing, but in contrast with the
      pairing-defective chk-2 mutant, SC assembly is not inhibited and generalized
      nonhomologous synapsis occurs. Extensive nonhomologous synapsis in htp-1; chk-2
      double mutants indicates that HTP-1 is required for the inhibition of SC assembly
      observed in chk-2 gonads. htp-1 mutants show a decreased abundance of nuclei
      exhibiting a polarized organization that normally accompanies establishment of
      pairing; analysis of htp-1; syp-2 double mutants suggests that HTP-1 is needed to
      prevent premature exit from this polarized nuclear organization and that this
      exit stops homology search. Further, based on experiments monitoring the
      formation of recombination intermediates and crossover products, we suggest that
      htp-1 mutants are defective in preventing the use of sister chromatids as
      recombination partners. We propose a model in which HTP-1 functions to establish
      or maintain multiple constraints that operate to ensure coordination of events
      leading to chiasma formation.

PMID- 16291647
TI  - HTP-1 coordinates synaptonemal complex assembly with homolog alignment during
      meiosis in C. elegans.
AB  - During meiosis, the mechanisms responsible for homolog alignment, synapsis, and
      recombination are precisely coordinated to culminate in the formation of
      crossovers capable of directing accurate chromosome segregation. An outstanding
      question is how the cell ensures that the structural hallmark of meiosis, the
      synaptonemal complex (SC), forms only between aligned pairs of homologous
      chromosomes. In the present study, we find that two closely related members of
      the him-3 gene family in Caenorhabditis elegans function as regulators of
      synapsis. HTP-1 functionally couples homolog alignment to its stabilization by
      synapsis by preventing the association of SC components with unaligned and
      immature chromosome axes; in the absence of the protein, nonhomologous contacts
      between chromosomes are inappropriately stabilized, resulting in extensive
      nonhomologous synapsis and a drastic decline in chiasma formation. In the absence
      of both HTP-1 and HTP-2, synapsis is abrogated per se and the early association
      of SC components with chromosomes observed in htp-1 mutants does not occur,
      suggesting a function for the proteins in licensing SC assembly. Furthermore, our
      results suggest that early steps of recombination occur in a narrow window of
      opportunity in early prophase that ends with SC assembly, resulting in a
      mechanistic coupling of the two processes to promote crossing over.

PMID- 16291649
TI  - A two-component phosphotransfer network involving ArcB, ArcA, and RssB
      coordinates synthesis and proteolysis of sigmaS (RpoS) in E. coli.
AB  - The general stress sigma factor sigma(S) (RpoS) in Escherichia coli is controlled
      at the levels of transcription, translation, and proteolysis. Here we demonstrate
      that the phosphorylated response regulator ArcA is a direct repressor of rpoS
      transcription that binds to two sites flanking the major rpoS promoter, with the
      upstream site overlapping an activating cAMP-CRP-binding site. The histidine
      sensor kinase ArcB not only phosphorylates ArcA, but also the sigma(S)
      proteolytic targeting factor RssB, and thereby stimulates sigma(S) proteolysis.
      Thus, ArcB/ArcA/RssB constitute a branched "three-component system", which
      coordinates rpoS transcription and sigma(S) proteolysis and thereby maintains low
      sigma(S) levels in rapidly growing cells. We suggest that the redox state of the
      quinones, which controls autophosphorylation of ArcB, not only monitors oxygen
      but also energy supply, and we show that the ArcB/ArcA/RssB system is involved in
      sigma(S) induction during entry into starvation conditions. Moreover, this
      induction is enhanced by a positive feedback that involves sigma(S)-dependent
      induction of ArcA, which further reduces sigma(S) proteolysis, probably by
      competing with RssB for residual phosphorylation by ArcB.

PMID- 16291648
TI  - Pollen development and fertilization in Arabidopsis is dependent on the MALE
      GAMETOGENESIS IMPAIRED ANTHERS gene encoding a type V P-type ATPase.
AB  - In flowering plants, development of the haploid male gametophytes (pollen grains)
      takes place in a specialized structure called the anther. Successful pollen
      development, and thus reproduction, requires high secretory activity in both
      anther tissues and pollen. In this paper, we describe a novel member of the
      eukaryotic type V subfamily (P(5)) of P-type ATPase cation pumps, the MALE
      GAMETOGENESIS IMPAIRED ANTHERS (MIA) gene. MIA protein is highly abundant in the
      endoplasmic reticulum and small vesicles of developing pollen grains and tapetum
      cells. T-DNA insertional mutants of MIA suffer from imbalances in cation
      homeostasis and exhibit a severe reduction in fertility. Mutant microspores fail
      to separate from tetrads and pollen grains are fragile with an abnormal
      morphology and altered cell wall structure. Disruption of MIA affects expression
      of genes essential for secretion as well as a high number of genes encoding cell
      wall proteins and membrane transporters. MIA functionally complements a mutant in
      the P(5) ATPase homolog SPF1 from Saccharomyces cerevisiae, suggesting a common
      function for P(5) ATPases in single and multicellular organisms. Our results
      suggest that MIA is required in the secretory pathway for proper secretion of
      vesicle cargo to the plasma membrane.

PMID- 16291650
TI  - Analysis of homologous gene clusters in Caenorhabditis elegans reveals striking
      regional cluster domains.
AB  - An algorithm for detecting local clusters of homologous genes was applied to the
      genome of Caenorhabditis elegans. Clusters of two or more homologous genes are
      abundant, totaling 1391 clusters containing 4607 genes, over one-fifth of all
      genes in C. elegans. Cluster genes are distributed unevenly in the genome, with
      the large majority located on autosomal chromosome arms, regions characterized by
      higher genetic recombination and more repeat sequences than autosomal centers and
      the X chromosome. Cluster genes are transcribed at much lower levels than average
      and very few have gross phenotypes as assayed by RNAi-mediated reduction of
      function. The molecular identity of cluster genes is unusual, with a
      preponderance of nematode-specific gene families that encode putative secreted
      and transmembrane proteins, and enrichment for genes implicated in xenobiotic
      detoxification and innate immunity. Gene clustering in Drosophila melanogaster is
      also substantial and the molecular identity of clustered genes follows a similar
      pattern. I hypothesize that autosomal chromosome arms in C. elegans undergo
      frequent local gene duplication and that these duplications support gene
      diversification and rapid evolution in response to environmental challenges.
      Although specific gene clusters have been documented in C. elegans, their
      abundance, genomic distribution, and unusual molecular identities were previously
      unrecognized.

PMID- 16291651
TI  - Multiple synergizing factors contribute to the strength of the CD8+ T cell
      response against listeriolysin O.
AB  - Immunodominance in CD8+ T cell responses against Listeria monocytogenes is a well
      recognized but still not fully understood phenomenon. From listeriolysin, the
      major virulence factor of L. monocytogenes, only a single epitope, pLLO91-99, is
      presented by MHC class I molecules in BALB/c mice which dominates the cytotoxic T
      cell response against this bacterial pathogen. To obtain more insights into the
      molecular and cellular mechanisms underlying immunodominance of this particular
      epitope, we compared the various steps involved in the presentation and
      recognition of pLLO91-99 derived from a wild-type toxin with an equivalent
      epitope from a mutated toxin. This fully functional variant contains within the
      pLLO91-99 epitope a conservative isoleucine to alanine replacement at the C
      terminal anchor residue which results in loss of antigenicity. The binding
      properties of the variant peptide to soluble Kd remained unaffected and cytotoxic
      T cells capable of recognizing the pLLO99A/Kd complex were detectable in BALB/c
      mice. However, such T cells required higher concentrations of antigen in order to
      be optimally activated in vitro. A comparison between the TAP translocation
      efficiency of wild-type and mutant peptide demonstrated that the mutation at the
      C-terminus leads to a reduced transportation rate. Furthermore, the amino acid
      substitution changes the in vitro proteasomal cleavage pattern, resulting in a
      reduced liberation of the correct peptide from a polypeptide precursor. Thus, in
      all assays employed the immunodominant epitope performs optimally while the
      variant was found to be inferior. The synergy of all these steps most likely is
      the decisive factor in the immunodominance of pLLO91-99.

PMID- 16291652
TI  - Mutational analysis of the SH2-kinase linker region of Bruton's tyrosine kinase
      defines alternative modes of regulation for cytoplasmic tyrosine kinase families.
AB  - Bruton's tyrosine kinase (Btk) plays critical roles in B cell development and
      activation. Mutations of Btk cause X-linked agammaglobulinemia (XLA) in humans
      and X-linked immunodeficiency in mice. An Src homology domain 2-kinase linker
      region exists in all Src, Abl, ZAP70/Syk and Btk/Tec non-receptor tyrosine kinase
      families. Missense mutations in the Btk linker region can cause XLA, supporting
      an essential role for this protein segment. We investigated the regulatory role
      of the linker region in Btk function by mutational analysis. XLA-causing
      mutations L369F and R372G abolished Btk-mediated calcium response without
      affecting Btk protein stability and kinase activity significantly. Although
      mutation of a well-conserved tryptophan (W260A) in the linker region of the Src
      family kinase Hck has been shown to cause a hyperactive kinase, an analogous
      mutation in Btk (W395A) dramatically decreased Btk kinase activity. Tyrosine
      phosphorylation in the linker region was previously shown to regulate the
      function of Abl and ZAP70/Syk kinases. Even though tyrosine phosphorylation was
      detected on tyrosine 375 in the Btk linker region, no significant alteration was
      observed in Btk-signaling activity and biological function when this tyrosine was
      mutated in DT-40 cells or in Y375F knock-in mice. Our data and previous studies
      suggest that each cytoplasmic tyrosine kinase family has evolved a unique
      strategy to utilize the linker region to regulate the function of the enzyme.

PMID- 16291653
TI  - Lack of induced co-stimulation as a result of complement receptor 2 (CR2)
      ligation on mouse splenic B cells.
AB  - B cells act as efficient antigen-presenting cells if they acquire antigen via
      membrane-bound Ig [termed the B cell receptor (BCR)]. Ligation of the BCR leads
      to antigen internalization, processing and presentation to CD4+ T cells in
      association with MHC class II molecules. Ligation of the BCR also leads to the
      generation of activation signals. One short-term consequence of this is the up
      regulation of co-stimulatory molecule expression by the B cell, allowing full T
      cell activation. Other antigen receptors expressed by B cells can also mediate
      efficient antigen presentation to CD4+ T cells. Ligating one such receptor,
      complement receptor 2 (CR2), has also been described to induce co-stimulatory
      molecule expression. If correct, this may have serious consequences for ensuring
      the specificity of the resultant B cell response. We have therefore investigated
      the effects of ligating both the BCR and CR2 independently of each other, as well
      as with reagents to cross-link the two receptors, in order to clarify these
      findings. In contrast to the effects seen upon BCR ligation, we find no evidence
      for co-stimulatory molecule up-regulation following CR2 ligation. As antigen
      presentation in the absence of co-stimulation may lead to the induction of
      tolerogenic or regulatory signals being delivered to T cell populations, these
      findings imply that the role of CR2 in B cell-mediated antigen presentation is
      different from that of the BCR.

PMID- 16291654
TI  - Expression of aberrant forms of CD22 on B lymphocytes in Cd22a lupus-prone mice
      affects ligand binding.
AB  - CD22 functions primarily as a negative regulator of B-cell receptor signaling.
      The Cd22a allele has been proposed as a candidate allele for murine systemic
      lupus erythematosus. In this study, we explored the possible expression of
      aberrant forms of CD22, which differ in the N-terminal sequences constituting the
      ligand-binding site due to synthesis of abnormally processed Cd22 mRNA, in
      several Cd22a mouse strains, including C57BL/6 Cd22 congenic mice. The staining
      pattern of splenic B cells obtained with CY34 anti-CD22 mAb, which was expected
      to bind poorly to the aberrant CD22, was more heterogeneous in Cd22(a) mice than
      in Cd22b mice. Moreover, CD22 detected on B cells of Cd22a mice was expressed
      more weakly and as a smaller-sized protein, compared with Cd22b mice.
      Significantly, analysis with a synthetic CD22 ligand demonstrated that Cd22a mice
      carried a larger proportion of CD22 that was not bound by cis ligands on the B
      cell surface than Cd22b mice. Finally, the study of C57BL/6 Cd22 congenic mice
      revealed that Cd22a B cells displayed a phenotype reminiscent of constitutively
      activated B cells (reduced surface IgM expression and augmented MHC class II
      expression), as reported for B cells expressing a mutant CD22 lacking the ligand
      binding domain. Our demonstration that Cd22a B cells express aberrant forms of
      CD22, which can potentially deregulate B-cell signaling because of their
      decreased ligand-binding capacity, provides further support for Cd22a as a
      potential candidate allele for murine systemic lupus erythematosus.

PMID- 16291655
TI  - Effect of IL-21 on NK cells derived from different umbilical cord blood
      populations.
AB  - IL-21 plays a role in the proliferation and maturation of NK cells developed from
      hematopoietic stem cells. In this study, we found that IL-21, in the presence of
      physiological concentration of hydrocortisone (HC), has a significant impact on
      the functions of NK cells derived from umbilical cord blood (CB) populations. We
      demonstrate that IL-21, in combination with Flt3-ligand, IL-15 and HC, induces
      high proliferative responses and, apart from enhancing NK-mediated cytotoxicity,
      it also induces a significant increase in lymphokine-activated killer activity of
      CB/CD34+-derived CD56+ cells. In addition, IL-21 induced changes in the CD56+
      cell cytokine secretion profile. Thus, we observed increased levels of IL-10 and
      granulocyte macrophage colony-stimulating factor, whereas tumor necrosis factor
      alpha levels decreased. IFN-gamma production was also modified by IL-21,
      depending on the presence or absence of IL-18. CB/CD34+ cells did not express the
      IL-21R ex vivo, but receptor expression was induced during their commitment to
      differentiation into CD56+ cells. Our data ascribe to IL-21 an essential role on
      NK cell development and function under conditions similar to the in vivo CB
      microenvironment.

PMID- 16291656
TI  - Evolution of class switch recombination function in fish activation-induced
      cytidine deaminase, AID.
AB  - Following activation of mammalian B cells, class switch recombination (CSR) and
      somatic hypermutation (SHM) of the Ig heavy chain (IgH) gene can improve the
      functions of the expressed antibodies. Activation-induced cytidine deaminase
      (AID) is the only known B cell-specific protein required for inducing CSR and SHM
      in mammals. Lower vertebrates have an AID homologue, and there is some evidence
      of SHM in vivo. However there is no evidence of CSR in the cartilaginous or bony
      fishes, and this may be due in part to a lack of cis-elements in the IgH gene
      that are the normal targets of AID-mediated recombination. We have tested whether
      bony fish (zebrafish and catfish) AID can mediate CSR and SHM in mammalian cells.
      As expected, ectopic expression of fish AID in mouse fibroblasts resulted in
      mutations in an introduced SHM reporter gene, indicating that fish AID can
      mediate SHM. Unexpectedly, expression of fish AID in mouse AID-/- B cells induced
      surface IgG expression as well as switched transcripts from Ig gene loci, clearly
      indicating that the fish AID protein can mediate CSR, at least in mouse cells.
      These results suggest that the AID protein acquired the ability to mediate CSR
      before the IgH locus evolved the additional exon clusters and switch regions that
      are the targets of recombination. We discuss how pleiotropic functions of
      specific domains within the AID protein may have facilitated the early evolution
      of CSR in lower vertebrates.

PMID- 16291657
TI  - B cell development in aging mice: lessons from mathematical modeling.
AB  - Previous studies have not completely clarified the precise defect that
      characterizes B cell development in aged animals. The question of which
      developmental mechanism is actually deficient in aging remains controversial. The
      goal of this study was to elucidate the effects of aging on bone marrow B cell
      population dynamics. We used mathematical modeling to predict the outcome of the
      different possible effects, and then compared these predictions to experimental
      data, to find the most plausible effects. Our model shows that the three main
      differences between B cell development in young and old mice are a decrease in
      the maximum number of cells in the pre-B compartment and increases in the rate of
      transition from cycling pre-B cells to resting pre-B cells and in the fractions
      of static cells included in the immature B cell subset.

PMID- 16291658
TI  - Sialylation regulates peripheral tolerance in CD4+ T cells.
AB  - Decreased binding by the 6C10 auto-antibody serves as a unique marker for CD4+ T
      cell unresponsiveness after the induction of T cell tolerance in Vbeta8.1 TCR
      transgenic mice. We further define the nature of the epitope recognized by the
      6C10 antibody to be a subset of Thy-1 bearing incompletely sialylated N-linked
      glycans, and furthermore, we demonstrate that tolerant CD4+ T cells have an
      increased degree of cell-surface sialylation. To test the significance of the
      altered glycosylation state identified by the 6C10 auto-antibody in the tolerant
      CD4+ T cell population, surface sialic acid was cleaved enzymatically. Treatment
      of purified peripheral CD4+ T cells with Vibrio cholerae sialidase (VCS) leads to
      increased 6C10 binding, significantly enhances proliferation in the tolerant CD4+
      population and corrects defects in phosphotyrosine signaling observed in the
      tolerant CD4+ T cell. Furthermore, in vivo administration of VCS enhances
      proliferation in both tolerant and naive CD4+ T cell subsets. These studies
      suggest that sialylation of glycoproteins on the surface of the CD4+ T cell
      contributes to the regulation of T cell responsiveness in the tolerant state.

PMID- 16291659
TI  - Preferential T(h)2 polarization by OCH is supported by incompetent NKT cell
      induction of CD40L and following production of inflammatory cytokines by
      bystander cells in vivo.
AB  - The altered glycolipid ligand OCH is a selective inducer of T(h)2 cytokines from
      NKT cells and a potent therapeutic reagent for T(h)1-mediated autoimmune
      diseases. Although we have previously shown the intrinsic molecular mechanism of
      preferential IL-4 production by OCH-stimulated NKT cells, little is known about
      the extrinsic regulatory network for IFN-gamma production. Here we demonstrate
      that OCH induces lower production of IFN-gamma, not only by NKT cells but also by
      NK cells compared with alpha-galactosylceramide. OCH induced lower IL-12
      production due to ineffective primary IFN-gamma and CD40 ligand expression by NKT
      cells, and resulted in lower secondary IFN-gamma induction. Co-injection of a sub
      optimal dose of IFN-gamma and stimulatory anti-CD40 mAb compensates for the lower
      induction of IL-12 by OCH administration. IL-12 converts OCH-induced cytokine
      expression from IL-4 predominance to IFN-gamma predominance. Furthermore, CpG
      oligodeoxynucleotide augmented IL-12 production when co-administrated with OCH,
      resulting in increased IFN-gamma production. Taken together, the lower IL-12
      production and subsequent lack of secondary IFN-gamma burst support the effective
      T(h)2 polarization of T cells by OCH. In addition, highlighted in this study is
      the characteristic property of OCH that can induce the differential production of
      IFN-gamma or IL-4 according to the availability of IL-12.

PMID- 16291660
TI  - Seeligeriolysin O, a protein toxin of Listeria seeligeri, stimulates macrophage
      cytokine production via Toll-like receptors in a profile different from that
      induced by other bacterial ligands.
AB  - Seeligeriolysin O (LSO), a member of cholesterol-dependent cytolysins of Listeria
      seeligeri, exhibits cytokine-inducing activity. In this study, we examined the
      profile of cytokines expressed in macrophages of mice after stimulation with full
      length form of recombinant LSO (rLSO530), C-terminal-truncated protein (rLSO483)
      and two authentic cytokine-inducing Toll-like receptor (TLR) ligands from
      bacteria, peptidoglycan (PGN) and LPS. Both rLSO530 and rLSO483 were able to
      induce IL-12 p40 and IL-12 p70 more strongly in macrophages than PGN or LPS. In
      contrast, IFN-beta and nitric oxide were induced by LPS but not by rLSO530,
      rLSO483 or PGN. In the presence of exogenously added IFN-beta, IL-12 p40 and IL
      12 p70 production was inhibited after LSO stimulation, but IL-12 p70 production
      was enhanced after PGN stimulation. Although LSO signaling appeared to be
      associated with both TLR2 and TLR4, the profile of cytokine production by LSO
      stimulation was distinct from those by stimulation with PGN or LPS. Thus, it was
      shown that LSO is a unique bacterial ligand that induces macrophage cytokine
      production in a manner different from PGN or LPS.

PMID- 16291661
TI  - A CCCH zinc finger conserved in a replication protein a homolog found in diverse
      Euryarchaeotes.
AB  - We describe a CCCH type of zinc finger domain in a replication protein A (RPA)
      homolog found in members of different lineages of the Euryarchaeota, a subdomain
      of Archaea. The zinc finger is characterized by CX(2)CX(8)CX(2)H, where X is any
      amino acid. Using MacRPA3, a representative of this new group of RPA in
      Methanosarcina acetivorans, we made two deletion mutants: a C-terminal deletion
      mutant lacking the zinc finger and an N-terminal deletion mutant containing the
      zinc finger domain. Whereas the N-terminal deletion mutant contained zinc at a
      level comparable to the wild-type protein level, the C-terminal deletion mutant
      was devoid of zinc. We further created four different mutants of MacRPA3 by
      replacing each of the four invariable amino acids in the zinc finger with
      alanine. Each single mutation at an invariable position resulted in a protein
      containing less than 35% of the zinc found in the wild-type protein. Circular
      dichroism spectra suggested that although the mutation at the first cysteine
      resulted in minor perturbation of protein structure, mutations at the other
      invariable positions led to larger structural changes. All proteins harboring a
      mutation at one of the invariable positions bound to single-stranded DNA weakly,
      and this translated into reduced capacity to stimulate DNA synthesis by M.
      acetivorans DNA polymerase BI. By subjecting the protein and its mutants to
      oxidizing and reducing conditions, we demonstrated that ssDNA binding by MacRPA3
      may be regulated by redox through the zinc finger. Thus, the zinc finger modules
      in euryarchaeal RPA proteins may serve as a means by which the function of these
      proteins is regulated in the cell.

PMID- 16291662
TI  - Vibrio cholerae ToxT independently activates the divergently transcribed aldA and
      tagA genes.
AB  - The Vibrio cholerae ToxT regulon includes the genes encoding cholera toxin (CT)
      and the toxin-coregulated pilus (TCP), which are the major virulence factors
      required for causing cholera disease and colonizing the upper small intestine of
      the host, respectively. The genes encoding CT, ctxAB, and the genes encoding the
      components of the TCP, tcpA to tcpJ, are organized within operons, upstream of
      which are DNA binding sites for the transcriptional activator ToxT. ToxT is a
      member of the large AraC/XylS family of transcriptional regulators and also
      activates transcription of five other genes whose roles in V. cholerae
      pathogenesis, if any, are poorly understood. acfA and acfD are divergently
      transcribed genes required for efficient colonization of the intestine.
      Transcriptional activation of acfA and acfD requires a pair of central ToxT
      binding sites in an inverted-repeat configuration for ToxT-directed transcription
      of both genes. tcpI has an unknown role in pathogenesis. aldA and tagA are
      divergently transcribed genes that also have unknown roles in pathogenesis. In
      this study, we map the aldA and tagA promoters and identify the ToxT binding
      sites upstream of each gene. Our results suggest that two ToxT binding sites in
      an inverted-repeat configuration are required for ToxT-directed transcription of
      tagA and that a single ToxT binding site is required for ToxT-directed
      transcription of aldA. Furthermore, to direct transcription of tagA and aldA,
      ToxT uses independent binding regions upstream of each gene, in contrast to what
      we previously found for the divergently transcribed acfA and acfD genes, which
      share ToxT binding sites between the two genes.

PMID- 16291663
TI  - Increased excision of the Salmonella prophage ST64B caused by a deficiency in Dam
      methylase.
AB  - Salmonella enterica mutants defective in Dam methylase are strongly attenuated in
      virulence and release a large amount of proteins to the extracellular medium. The
      extent to which these two phenotypes are linked is unknown. Using a proteomic
      approach, we identified Sb6, Sb13, and Sb36 as proteins present in larger amounts
      in culture supernatants of an S. enterica serovar Typhimurium dam mutant than in
      those of the wild-type strain. These three proteins are encoded in the Salmonella
      prophage ST64B. Higher amounts of ST64B phage DNA and tailless viral capsids were
      also detected in supernatant extracts of the dam mutant, suggesting that Dam
      methylation negatively regulates the excision of ST64B. Reverse transcription-PCR
      analysis revealed that the expression of two ST64B genes encoding a putative
      antirepressor and a phage replication protein increases in the dam mutant. The
      SOS response also augments the excision of ST64B. Infection assays performed with
      phage-cured strains demonstrated that ST64B does not carry genes required for
      virulence in the mouse model. Evidence was also obtained discarding a
      relationship between the high excision of ST64B and the envelope instability or
      virulence attenuation phenotype. Taken together, these data indicate that ST64B
      excises at a high rate in dam mutants due to the loss of repression exerted by
      Dam on phage genes and induction of the SOS response characteristic of these
      mutants. The exacerbated excision of ST64B does not however contribute to the
      incapacity of dam mutants to cause disease.

PMID- 16291664
TI  - Mutations that activate the silent bgl operon of Escherichia coli confer a growth
      advantage in stationary phase.
AB  - Wild-type strains of Escherichia coli are unable to utilize aromatic beta
      glucosides such as arbutin and salicin because the major genetic system that
      encodes the functions for their catabolism, the bgl operon, is silent and
      uninducible. We show that strains that carry an activated bgl operon exhibit a
      growth advantage over the wild type in stationary phase in the presence of the
      rpoS819 allele that causes attenuated rpoS regulon expression. Our results
      indicate a possible evolutionary advantage in retaining the silent bgl operon by
      wild-type bacteria.

PMID- 16291665
TI  - A positive regulatory loop controls expression of the locus of enterocyte
      effacement-encoded regulators Ler and GrlA.
AB  - The formation of attaching and effacing (A/E) lesions on intestinal epithelial
      cells is an essential step in the pathogenesis of human enteropathogenic and
      enterohemorrhagic Escherichia coli and of the mouse pathogen Citrobacter
      rodentium. The genes required for the development of the A/E phenotype are
      located within a pathogenicity island known as the locus of enterocyte effacement
      (LEE). The LEE-encoded transcriptional regulators Ler, an H-NS-like protein, and
      GrlA, a member of a novel family of transcriptional activators, positively
      control the expression of the genes located in the LEE and their corresponding
      virulence. In this study, we used C. rodentium as a model to study the mechanisms
      controlling the expression of Ler and GrlA. By deletion analysis of the ler and
      grlRA regulatory regions and complementation experiments, negative and positive
      cis-acting regulatory motifs were identified that are essential for the
      regulation of both genes. This analysis confirmed that GrlA is required for the
      activation of ler, but it also showed that Ler is required for the expression of
      grlRA, revealing a novel regulatory loop controlling the optimal expression of
      virulence genes in A/E pathogens. Furthermore, our results indicate that Ler and
      GrlA induce the expression of each other by, at least in part, counteracting the
      repression mediated by H-NS. However, whereas GrlA is still required for the
      optimal expression of ler even in the absence of H-NS, Ler is not needed for the
      expression of grlRA in the absence of H-NS. This type of transcriptional positive
      regulatory loop represents a novel mechanism in pathogenic bacteria that is
      likely required to maintain an appropriate spatiotemporal transcriptional
      response during infection.

PMID- 16291666
TI  - sinI- and expR-dependent quorum sensing in Sinorhizobium meliloti.
AB  - Quorum sensing (QS) in Sinorhizobium meliloti, the N-fixing bacterial symbiont of
      Medicago host plants, involves at least half a dozen different N-acyl homoserine
      lactone (AHL) signals and perhaps an equal number of AHL receptors. The
      accumulation of 55 proteins was found to be dependent on SinI, the AHL synthase,
      and/or on ExpR, one of the AHL receptors. Gas chromatography-mass spectrometry
      and electrospray ionization tandem mass spectrometry identified 3-oxo-C(14)
      homoserine lactone (3-oxo-C(14)-HSL), C(16)-HSL, 3-oxo-C(16)-HSL, C(16:1)-HSL,
      and 3-oxo-C(16:1)-HSL as the sinI-dependent AHL QS signals accumulated by the
      8530 expR(+) strain under the conditions used for proteome analysis. The 8530
      expR(+) strain secretes additional, unidentified QS-active compounds. Addition of
      200 nM C(14)-HSL or C(16:1)-HSL, two of the known SinI AHLs, affected the levels
      of 75% of the proteins, confirming that their accumulation is QS regulated. A
      number of the QS-regulated proteins have functions plausibly related to symbiotic
      interactions with the host, including ExpE6, IdhA, MocB, Gor, PckA, LeuC, and
      AglE. Seven of 10 single-crossover beta-glucuronidase (GUS) transcriptional
      reporters in genes corresponding to QS-regulated proteins showed significantly
      different activities in the sinI and expR mutant backgrounds and in response to
      added SinI AHLs. The sinI mutant and several of the single-crossover strains were
      significantly delayed in the ability to initiate nodules on the primary root of
      the host plant, Medicago truncatula, indicating that sinI-dependent QS regulation
      and QS-regulated proteins contribute importantly to the rate or efficiency of
      nodule initiation. The sinI and expR mutants were also defective in surface
      swarming motility. The sinI mutant was restored to normal swarming by 5 nM
      C(16:1)-HSL.

PMID- 16291667
TI  - Enterobacterial repetitive intergenic consensus sequence repeats in yersiniae:
      genomic organization and functional properties.
AB  - Genome-wide analyses carried out in silico revealed that the DNA repeats called
      enterobacterial repetitive intergenic consensus sequences (ERICs), which are
      present in several Enterobacteriaceae, are overrepresented in yersiniae. From the
      alignment of DNA regions from the wholly sequenced Yersinia enterocolitica 8081
      and Yersinia pestis CO92 strains, we could establish that ERICs are miniature
      mobile elements whose insertion leads to duplication of the dinucleotide TA.
      ERICs feature long terminal inverted repeats (TIRs) and can fold as RNA into
      hairpin structures. The proximity to coding regions suggests that most Y.
      enterocolitica ERICs are cotranscribed with flanking genes. Elements which either
      overlap or are located next to stop codons are preferentially inserted in the
      same (or B) orientation. In contrast, ERICs located far apart from open reading
      frames are inserted in the opposite (or A) orientation. The expression of genes
      cotranscribed with A- and B-oriented ERICs has been monitored in vivo. In mRNAs
      spanning B-oriented ERICs, upstream gene transcripts accumulated at lower levels
      than downstream gene transcripts. This difference was abolished by treating cells
      with chloramphenicol. We hypothesize that folding of B-oriented elements is
      impeded by translating ribosomes. Consequently, upstream RNA degradation is
      triggered by the unmasking of a site for the RNase E located in the right-hand
      TIR of ERIC. A-oriented ERICs may act in contrast as upstream RNA stabilizers or
      may have other functions. The hypothesis that ERICs act as regulatory RNA
      elements is supported by analyses carried out in Yersinia strains which either
      lack ERIC sequences or carry alternatively oriented ERICs at specific loci.

PMID- 16291668
TI  - The alternative sigma factor AlgT represses Pseudomonas aeruginosa flagellum
      biosynthesis by inhibiting expression of fleQ.
AB  - Pseudomonas aeruginosa poses a serious risk in individuals suffering from cystic
      fibrosis (CF). Strains colonizing the CF lung are generally motile but frequently
      convert to a nonmotile phenotype as the disease progresses. In many cases, this
      is coordinately regulated with the overproduction of the exopolysaccharide
      alginate. Both the expression of alginate (mucoidy) and the loss of flagellum
      synthesis may provide the bacterium with a selective advantage in the CF lung.
      Previously published data showed that the regulation of alginate production and
      flagellum biosynthesis in the CF isolate FRD1 is inversely controlled by the
      alternative sigma factor AlgT. In this study, we observed that in CF isolates,
      the mucoid and the nonmotile phenotypes occur predominantly together. Using
      microarrays, we compared the transcriptomes of isogenic AlgT(+) and AlgT(-) P.
      aeruginosa and discovered that AlgT significantly downregulated the majority of
      flagellar genes. A pronounced inhibitory effect was observed in several genes
      essential for proper flagellum expression, including fleQ, which encodes an
      essential flagellar regulator. The microarray data were confirmed by reverse
      transcriptase PCR analysis and promoter fusion assays in isogenic AlgT(+) and
      AlgT(-) strains. Transmission electron microscopy, motility assays, and Western
      blots showed that ectopic expression of FleQ in mucoid, nonmotile CF isolates
      restored flagellum biosynthesis and motility. Together, these data show that AlgT
      mediates the negative control of flagellum expression by inhibiting the
      expression of the flagellar regulator fleQ.

PMID- 16291669
TI  - CheX is a phosphorylated CheY phosphatase essential for Borrelia burgdorferi
      chemotaxis.
AB  - Motility and chemotaxis are believed to be important in the pathogenesis of Lyme
      disease caused by the spirochete Borrelia burgdorferi. Controlling the
      phosphorylation state of CheY, a response regulator protein, is essential for
      regulating bacterial chemotaxis and motility. Rapid dephosphorylation of
      phosphorylated CheY (CheY-P) is crucial for cells to respond to environmental
      changes. CheY-P dephosphorylation is accomplished by one or more phosphatases in
      different species, including CheZ, CheC, CheX, FliY, and/or FliY/N. Only a cheX
      phosphatase homolog has been identified in the B. burgdorferi genome. However, a
      role for cheX in chemotaxis has not been established in any bacterial species.
      Inactivating B. burgdorferi cheX by inserting a flgB-kan cassette resulted in
      cells (cheX mutant cells) with a distinct motility phenotype. While wild-type
      cells ran, paused (stopped or flexed), and reversed, the cheX mutant cells
      continuously flexed and were not able to run or reverse. Furthermore, swarm plate
      and capillary tube chemotaxis assays demonstrated that cheX mutant cells were
      deficient in chemotaxis. Wild-type chemotaxis and motility were restored when
      cheX mutant cells were complemented with a shuttle vector expressing CheX.
      Furthermore, CheX dephosphorylated CheY3-P in vitro and eluted as a homodimer in
      gel filtration chromatography. These findings demonstrated that B. burgdorferi
      CheX is a CheY-P phosphatase that is essential for chemotaxis and motility, which
      is consistent with CheX being the only CheY-P phosphatase in the B. burgdorferi
      chemotaxis signal transduction pathway.

PMID- 16291670
TI  - The plmS2-encoded cytochrome P450 monooxygenase mediates hydroxylation of
      phoslactomycin B in Streptomyces sp. strain HK803.
AB  - Streptomyces sp. strain HK803 produces six analogues of phoslactomycin (Plm A
      through Plm F). With the exception of Plm B, these analogues contain a C-18
      hydroxyl substituent esterified with a range of short-alkyl-chain carboxylic
      acids. Deletion of the plmS(2) open reading frame (ORF), showing high sequence
      similarity to bacterial cytochrome P450 monooxygenases (CYPs), from the Plm
      biosynthetic gene cluster has previously resulted in an NP1 mutant producing only
      Plm B (N. Palaniappan, B. S. Kim, Y. Sekiyama, H. Osada, and K. A. Reynolds, J.
      Biol. Chem. 278:35552-35557, 2003). Herein, we report that a complementation
      experiment with an NP1 derivative (NP2), using a recombinant conjugative plasmid
      carrying the plmS(2) ORF downstream of the ermE* constitutive promoter (pMSG1),
      restored production of Plm A and Plm C through Plm F. The 1.2-kbp plmS(2) ORF was
      also expressed efficiently as an N-terminal polyhistidine-tagged protein in
      Streptomyces coelicolor. The recombinant PlmS(2) converted Plm B to C-18-hydroxy
      Plm B (Plm G). PlmS(2) was highly specific for Plm B and unable to process a
      series of derivatives in which either the lactone ring was hydrolyzed or the C-9
      phosphate ester was converted to C-9/C-11 phosphorinane. This biochemical
      analysis and complementation experiment are consistent with a proposed Plm
      biosynthetic pathway in which the penultimate step is hydroxylation of the
      cyclohexanecarboxylic acid-derived side chain of Plm B by PlmS(2) (the resulting
      Plm G is then esterified to provide Plm A and Plm C through Plm F). Kinetic
      parameters for Plm B hydroxylation by PlmS(2) (K(m) of 45.3 +/- 9.0 microM and
      k(cat) of 0.27 +/- 0.04 s(-1)) are consistent with this step being a rate
      limiting step in the biosynthetic pathway. The penultimate pathway intermediate
      Plm G has less antifungal activity than Plm A through Plm F and is not observed
      in fermentations of either the wild-type strain or NP2/pMSG1.

PMID- 16291671
TI  - Identification and characterization of a novel outer membrane protein (OMP J) of
      Moraxella catarrhalis that exists in two major forms.
AB  - Moraxella catarrhalis is a common commensal of the human respiratory tract that
      has been associated with a number of disease states, including acute otitis media
      in children and exacerbations of chronic obstructive pulmonary disease in adults.
      During studies to investigate the outer membrane proteins of this bacterium, two
      novel major proteins, of approximately 19 kDa and 16 kDa (named OMP J1 and OMP
      J2, respectively), were identified. Further analysis indicated that these two
      proteins possessed almost identical gene sequences, apart from two
      insertion/deletion events in predicted external loops present within the putative
      barrel-like structure of the proteins. The development of a PCR screening
      strategy found a 100% (96/96) incidence for the genes encoding the OMP J1 and OMP
      J2 proteins within a set of geographically diverse M. catarrhalis isolates, as
      well as a significant association of OMP J1/OMP J2 with both the genetic lineage
      and the complement resistance phenotype (Fisher's exact test; P < 0.01).
      Experiments using two DeltaompJ2 mutants (one complement resistant and the other
      complement sensitive) indicated that both were less easily cleared from the lungs
      of mice than were their isogenic wild-type counterparts, with a significant
      difference in bacterial clearance being observed for the complement-resistant
      isolate but not for its isogenic DeltaompJ2 mutant (unpaired Student's t test; P
      < 0.001 and P = 0.32). In this publication, we characterize a novel outer
      membrane protein of Moraxella catarrhalis which exists in two variant forms
      associated with particular genetic lineages, and both forms are suggested to
      contribute to bacterial clearance from the lungs.

PMID- 16291672
TI  - Demonstration of cotranscription and 1-methyl-3-nitroso-nitroguanidine induction
      of a 30-gene operon of Borrelia burgdorferi: evidence that the 32-kilobase
      circular plasmids are prophages.
AB  - The Borrelia genome is comprised of linear and circular elements, including a
      group of 32-kb circular plasmids (cp32s). Earlier analyses identified a
      bacteriophage, varphiBB-1, that may package cp32s, suggesting that these plasmids
      are prophages. cp32-8, cp32-9, and cp32-1 (plasmids L, N, and P, respectively)
      encode virulence factors such as the factor H binding, OspE proteins (BBL39,
      BBN38, and BBP38). Here the expression patterns of cp32-8 open reading frames
      (ORFs) in in vitro-cultivated 1-methyl-3-nitroso-nitroguanidine (MNNG)-treated
      and untreated spirochetes and during infection were assessed. ORFs BBL42 through
      BBL28, which encode several bacteriophage protein homologs, were found to be
      cotranscribed and expression was upregulated by MNNG. Immunoblotting revealed
      that MNNG-induced transcription led to increased protein production. The
      expression of several genes that reside outside of the BBL42-BBL28 operon was not
      affected by MNNG. Some of these genes, including OspE (BBL39), appear to
      represent morons. Real-time reverse transcription-PCR of spirochetes in mouse
      tissue revealed that although the phage operon was not induced during infection,
      transcription of BBL23 (previously designated BlyA), a putative holin, was
      upregulated. This observation indicates that some genes within the operon can be
      independently transcribed from internal promoters. Additional transcriptional
      analyses of the operon identified multiple transcriptional start sites and
      provided evidence for the expression of a homologous operon from other cp32s. The
      data support the hypothesis put forth by C. Eggers and D. S. Samuels (J.
      Bacteriol. 181:7308-7313, 1999) that the cp32s are prophages, a finding with
      broad implications for our understanding of Borrelia pathogenesis and Borrelia
      genome evolution.

PMID- 16291673
TI  - Growth substrate- and phase-specific expression of biphenyl, benzoate, and C1
      metabolic pathways in Burkholderia xenovorans LB400.
AB  - Recent microarray experiments suggested that Burkholderia xenovorans LB400, a
      potent polychlorinated biphenyl (PCB)-degrading bacterium, utilizes up to three
      apparently redundant benzoate pathways and a C(1) metabolic pathway during
      biphenyl and benzoate metabolism. To better characterize the roles of these
      pathways, we performed quantitative proteome profiling of cells grown on
      succinate, benzoate, or biphenyl and harvested during either mid-logarithmic
      growth or the transition between the logarithmic and stationary growth phases.
      The Bph enzymes, catabolizing biphenyl, were approximately 16-fold more abundant
      in biphenyl- versus succinate-grown cells. Moreover, the upper and lower bph
      pathways were independently regulated. Expression of each benzoate pathway
      depended on growth substrate and phase. Proteins specifying catabolism via
      benzoate dihydroxylation and catechol ortho-cleavage (ben-cat pathway) were
      approximately an order of magnitude more abundant in benzoate- versus biphenyl
      grown cells at the same growth phase. The chromosomal copy of the benzoyl
      coenzyme A (CoA) (box(C)) pathway was also expressed during growth on biphenyl:
      Box(C) proteins were approximately twice as abundant as Ben and Cat proteins
      under these conditions. By contrast, proteins of the megaplasmid copy of the
      benzoyl-CoA (box(M)) pathway were only detected in transition-phase benzoate
      grown cells. Other proteins detected at increased levels in benzoate- and
      biphenyl-grown cells included general stress response proteins potentially
      induced by reactive oxygen species formed during aerobic aromatic catabolism.
      Finally, C(1) metabolic enzymes were present in biphenyl-grown cells during
      transition phase. This study provides insights into the physiological roles and
      integration of apparently redundant catabolic pathways in large-genome bacteria
      and establishes a basis for investigating the PCB-degrading abilities of this
      strain.

PMID- 16291674
TI  - Molecular analysis and organization of the sigmaB operon in Staphylococcus
      aureus.
AB  - The alternative sigma factor sigma(B) of Staphylococcus aureus controls the
      expression of a variety of genes, including virulence determinants and global
      regulators. Genetic manipulations and transcriptional start point (TSP) analyses
      showed that the sigB operon is transcribed from at least two differentially
      controlled promoters: a putative sigma(A)-dependent promoter, termed sigB(p1),
      giving rise to a 3.6-kb transcript covering sa2059-sa2058-rsbU-rsbV-rsbW-sigB,
      and a sigma(B)-dependent promoter, sigB(p3), initiating a 1.6-kb transcript
      covering rsbV-rsbW-sigB. TSP and promoter-reporter gene fusion experiments
      indicated that a third promoter, tentatively termed sigB(p2) and proposed to lead
      to a 2.5-kb transcript, including rsbU-rsbV-rsbW-sigB, might govern the
      expression of the sigB operon. Environmental stresses, such as heat shock and
      salt stress, induced a rapid response within minutes from promoters sigB(p1) and
      sigB(p3). In vitro, the sigB(p1) promoter was active in the early growth stages,
      while the sigB(p2) and sigB(p3) promoters produced transcripts throughout the
      growth cycle, with sigB(p3) peaking around the transition state between
      exponential growth and stationary phase. The amount of sigB transcripts, however,
      did not reflect the concentration of sigma(B) measured in cell extracts, which
      remained constant over the entire growth cycle. In a guinea pig cage model of
      infection, sigB transcripts were as abundant 2 and 8 days postinoculation as
      values found in vitro, demonstrating that sigB is indeed transcribed during the
      course of infection. Physical interactions between staphylococcal RsbU-RsbV, RsbV
      RsbW, and RsbW-sigma(B) were inferred from a yeast (Saccharomyces cerevisiae) two
      hybrid approach, indicating the presence of a partner-switching mechanism in the
      sigma(B) activation cascade similar to that of Bacillus subtilis. The finding
      that overexpression of RsbU was sufficient to trigger an immediate and strong
      activation of sigma(B), however, signals a relevant difference in the regulation
      of sigma(B) activation between B. subtilis and S. aureus in the cascade upstream
      of RsbU.

PMID- 16291675
TI  - Decaprenylphosphoryl arabinofuranose, the donor of the D-arabinofuranosyl
      residues of mycobacterial arabinan, is formed via a two-step epimerization of
      decaprenylphosphoryl ribose.
AB  - The major cell wall polysaccharide of mycobacteria is a branched-chain
      arabinogalactan in which arabinan chains are attached to the 5 carbon of some of
      the 6-linked galactofuranose residues; these arabinan chains are composed
      exclusively of D-arabinofuranose (Araf) residues. The immediate precursor of the
      polymerized Araf is decaprenylphosphoryl-D-Araf, which is derived from 5
      phosphoribose 1-diphosphate (pRpp) in an undefined manner. On the basis of time
      course, feedback, and chemical reduction experiment results we propose that
      decaprenylphosphoryl-Araf is synthesized by the following sequence of events. (i)
      pRpp is transferred to a decaprenyl-phosphate molecule to form
      decaprenylphosphoryl-beta-D-5-phosphoribose. (ii) Decaprenylphosphoryl-beta-D-5
      phosphoribose is dephosphorylated to form decaprenylphosphoryl-beta-D-ribose.
      (iii) The hydroxyl group at the 2 position of the ribose is oxidized and is
      likely to form decaprenylphosphoryl-2-keto-beta-D-erythro-pentofuranose. (iv)
      Decaprenylphosphoryl-2-keto-beta-D-erythro-pentofuranose is reduced to form
      decaprenylphosphoryl-beta-D-Araf. Thus, the epimerization of the ribosyl to an
      arabinosyl residue occurs at the lipid-linked level; this is the first report of
      an epimerase that utilizes a lipid-linked sugar as a substrate. On the basis of
      similarity to proteins implicated in the arabinosylation of the Azorhizobium
      caulidans nodulation factor, two genes were cloned from the Mycobacterium
      tuberculosis genome and expressed in a heterologous host, and the protein was
      purified. Together, these proteins (Rv3790 and Rv3791) are able to catalyze the
      epimerization, although neither protein individually is sufficient to support the
      activity.

PMID- 16291676
TI  - Comparative analysis of two classes of quorum-sensing signaling systems that
      control production of extracellular proteins and secondary metabolites in Erwinia
      carotovora subspecies.
AB  - In Erwinia carotovora subspecies, N-acyl homoserine lactone (AHL) controls the
      expression of various traits, including extracellular enzyme/protein production
      and pathogenicity. We report here that E. carotovora subspecies possess two
      classes of quorum-sensing signaling systems defined by the nature of the major
      AHL analog produced as well as structural and functional characteristics of AHL
      synthase (AhlI) and AHL receptor (ExpR). Class I strains represented by E.
      carotovora subsp. atroseptica strain Eca12 and E. carotovora subsp. carotovora
      strains EC153 and SCC3193 produce 3-oxo-C8-HL (N-3-oxooctanoyl-l-homoserine
      lactone) as the major AHL analog as well as low but detectable levels of 3-oxo-C6
      HL (N-3-oxohexanoyl-l-homoserine lactone). In contrast, the members of class II
      (i.e., E. carotovora subsp. betavasculorum strain Ecb168 and E. carotovora subsp.
      carotovora strains Ecc71 and SCRI193) produce 3-oxo-C6-HL as the major analog.
      ExpR species of both classes activate rsmA (Rsm, repressor of secondary
      metabolites) transcription and bind rsmA DNA. Gel mobility shift assays with
      maltose-binding protein (MBP)-ExpR(71) and MBP-ExpR(153) fusion proteins show
      that both bind a 20-mer sequence present in rsmA. The two ExpR functions (i.e.,
      expR-mediated activation of rsmA expression and ExpR binding with rsmA DNA) are
      inhibited by AHL. The AHL effects are remarkably specific in that expR effect of
      EC153, a strain belonging to class I, is counteracted by 3-oxo-C8-HL but not by 3
      oxo-C6-HL. Conversely, the expR effect of Ecc71, a strain belonging to class II,
      is neutralized by 3-oxo-C6-HL but not by 3-oxo-C8-HL. The AHL responses
      correlated with expR-mediated inhibition of exoprotein and secondary metabolite
      production.

PMID- 16291677
TI  - Minimal functions and physiological conditions required for growth of salmonella
      enterica on ethanolamine in the absence of the metabolosome.
AB  - During growth on ethanolamine, Salmonella enterica synthesizes a multimolecular
      structure that mimics the carboxysome used by some photosynthetic bacteria to fix
      CO(2). In S. enterica, this carboxysome-like structure (hereafter referred to as
      the ethanolamine metabolosome) is thought to contain the enzymatic machinery
      needed to metabolize ethanolamine into acetyl coenzyme A (acetyl-CoA). Analysis
      of the growth behavior of mutant strains of S. enterica lacking specific
      functions encoded by the 17-gene ethanolamine utilization (eut) operon
      established the minimal biochemical functions needed by this bacterium to use
      ethanolamine as a source of carbon and energy. The data obtained support the
      conclusion that the ethanolamine ammnonia-lyase (EAL) enzyme (encoded by the
      eutBC genes) and coenzyme B(12) are necessary and sufficient to grow on
      ethanolamine. We propose that the EutD phosphotransacetylase and EutG alcohol
      dehydrogenase are important to maintain metabolic balance. Glutathione (GSH) had
      a strong positive effect that compensated for the lack of the EAL reactivase EutA
      protein under aerobic growth on ethanolamine. Neither GSH nor EutA was needed
      during growth on ethanolamine under reduced-oxygen conditions. GSH also
      stimulated growth of a strain lacking the acetaldehyde dehydrogenase (EutE)
      enzyme. The role of GSH in ethanolamine catabolism is complex and requires
      further investigation. Our data show that the ethanolamine metabolosome is not
      involved in the biochemistry of ethanolamine catabolism. We propose the
      metabolosome is needed to concentrate low levels of ethanolamine catabolic
      enzymes, to keep the level of toxic acetaldehyde low, to generate enough acetyl
      CoA to support cell growth, and to maintain a pool of free CoA.

PMID- 16291678
TI  - Fine structure of the Deinococcus radiodurans nucleoid revealed by cryoelectron
      microscopy of vitreous sections.
AB  - Transmission electron microscopy revealed that the nucleoid of the extremely
      radioresistant bacteria Deinococcus radiodurans may adopt an unusual ring shape.
      This led to the hypothesis that the tight toroidal package of the D. radiodurans
      genome might contribute to radioresistance by preventing diffusion of ends of
      double-stranded DNA breaks. The molecular arrangement of DNA in the nucleoid,
      which must be determined to test this hypothesis, is not discernible by
      conventional methods of electron microscopy. We have applied cryoelectron
      microscopy of vitreous sections and found that the DNA arrangement in D.
      radiodurans differs from toroidal spooling. Diffuse coralline nucleoids of
      exponentially growing D. radiodurans do not reveal any particular molecular
      order. Electron-dense granules are generally observed in the centers of
      nucleoids. In stationary-phase cells, the nucleoid segregates from cytoplasm and
      DNA filaments show locally parallel arrangements, with increasing aspects of
      cholesteric liquid crystalline phase upon prolonged starvation. The relevance of
      the observed nucleoid organization to the radiation resistance of D. radiodurans
      is discussed.

PMID- 16291679
TI  - Characterization of Bacillus anthracis germinant receptors in vitro.
AB  - Bacillus anthracis begins its infectious cycle as a metabolically dormant cell
      type, the endospore. Upon entry into a host, endospores rapidly differentiate
      into vegetative bacilli through the process of germination, thus initiating
      anthrax. Elucidation of the signals that trigger germination and the receptors
      that recognize them is critical to understanding the pathogenesis of B.
      anthracis. Individual mutants deficient in each of the seven putative germinant
      receptor-encoding loci were constructed via temperature-dependent, plasmid
      insertion mutagenesis and used to correlate these receptors with known germinant
      molecules. These analyses showed that the GerK and GerL receptors are jointly
      required for the alanine germination pathway and also are individually required
      for recognition of either proline and methionine (GerK) or serine and valine
      (GerL) as cogerminants in combination with inosine. The germinant specificity of
      GerS was refined from a previous study in a nonisogenic background since it was
      required only for germination in response to aromatic amino acid cogerminants.
      The gerA and gerY loci were found to be dispensable for recognition of all known
      germinant molecules. In addition, we show that the promoter of each putative
      germinant receptor operon, except that of the gerA locus, is active during
      sporulation. A current model of B. anthracis endospore germination is presented.

PMID- 16291681
TI  - Involvement of SenC in assembly of cytochrome c oxidase in Rhodobacter
      capsulatus.
AB  - SenC, a Sco1 homolog found in the purple photosynthetic bacteria, has been
      implicated in affecting photosynthesis and respiratory gene expression, as well
      as assembly of cytochrome c oxidase. In this study, we show that SenC from
      Rhodobacter capsulatus is involved in the assembly of a fully functional cbb(3)
      type cytochrome c oxidase, as revealed by decreased cytochrome c oxidase activity
      in a senC mutant. We also show that a putative copper-binding site in SenC is
      required for activity and that a SenC deletion phenotype can be rescued by the
      addition of exogenous copper to the growth medium. In addition, we demonstrate
      that a SenC mutation has an indirect effect on gene expression caused by a
      reduction in cytochrome c oxidase activity. A model is proposed whereby a
      reduction in cytochrome c oxidase activity impedes the flow of electrons through
      the respiratory pathway, thereby affecting the oxidation/reduction state of the
      ubiquinone pool, leading to alterations of photosystem and respiratory gene
      expression.

PMID- 16291680
TI  - Genome-wide transcriptional analysis of the phosphate starvation stimulon of
      Bacillus subtilis.
AB  - Bacillus subtilis responds to phosphate starvation stress by inducing the PhoP
      and SigB regulons. While the PhoP regulon provides a specific response to
      phosphate starvation stress, maximizing the acquisition of phosphate (P(i)) from
      the environment and reducing the cellular requirement for this essential
      nutrient, the SigB regulon provides nonspecific resistance to stress by
      protecting essential cellular components, such as DNA and membranes. We have
      characterized the phosphate starvation stress response of B. subtilis at a genome
      wide level using DNA macroarrays. A combination of outlier and cluster analyses
      identified putative new members of the PhoP regulon, namely, yfkN (2',3' cyclic
      nucleotide 2'-phosphodiesterase), yurI (RNase), yjdB (unknown), and vpr
      (extracellular serine protease). YurI is thought to be responsible for the
      nonspecific degradation of RNA, while the activity of YfkN on various nucleotide
      phosphates suggests that it could act on substrates liberated by YurI, which
      produces 3' or 5' phosphoribonucleotides. The putative new PhoP regulon members
      are either known or predicted to be secreted and are likely to be important for
      the recovery of inorganic phosphate from a variety of organic sources of
      phosphate in the environment.

PMID- 16291682
TI  - Identification of Erwinia amylovora genes induced during infection of immature
      pear tissue.
AB  - The enterobacterium Erwinia amylovora is a devastating plant pathogen causing
      necrotrophic fire blight disease of apple, pear, and other rosaceous plants. In
      this study, we used a modified in vivo expression technology system to identify
      E. amylovora genes that are activated during infection of immature pear tissue, a
      process that requires the major pathogenicity factors of this organism. We
      identified 394 unique pear fruit-induced (pfi) genes on the basis of sequence
      similarity to known genes and separated them into nine putative function groups
      including host-microbe interactions (3.8%), stress response (5.3%), regulation
      (11.9%), cell surface (8.9%), transport (13.5%), mobile elements (1.0%),
      metabolism (20.3%), nutrient acquisition and synthesis (15.5%), and unknown or
      hypothetical proteins (19.8%). Known virulence genes, including hrp/hrc
      components of the type III secretion system, the major effector gene dspE, type
      II secretion, levansucrase (lsc), and regulators of levansucrase and amylovoran
      biosynthesis, were upregulated during pear tissue infection. Known virulence
      factors previously identified in E. (Pectobacterium) carotovora and Pseudomonas
      syringae were identified for the first time in E. amylovora and included HecA
      hemagglutinin family adhesion, Peh polygalacturonase, new effector HopPtoC(EA),
      and membrane-bound lytic murein transglycosylase MltE(EA). An insertional
      mutation within hopPtoC(EA) did not result in reduced virulence; however, an
      mltE(EA) knockout mutant was reduced in virulence and growth in immature pears.
      This study suggests that E. amylovora utilizes a variety of strategies during
      plant infection and to overcome the stressful and poor nutritional environment of
      its plant hosts.

PMID- 16291683
TI  - Genetic and biochemical analysis of the twin-arginine translocation pathway in
      halophilic archaea.
AB  - The twin-arginine translocation (Tat) pathway is present in a wide variety of
      prokaryotes and is capable of exporting partially or fully folded proteins from
      the cytoplasm. Although diverse classes of proteins are transported via the Tat
      pathway, in most organisms it facilitates the secretion of a relatively small
      number of substrates compared to the Sec pathway. However, computational evidence
      suggests that haloarchaea route nearly all secreted proteins to the Tat pathway.
      We have expanded previous computational analyses of the haloarchaeal Tat pathway
      and initiated in vivo characterization of the Tat machinery in a model
      haloarchaeon, Haloferax volcanii. Consistent with the predicted usage of the this
      pathway in the haloarchaea, we determined that three of the four identified tat
      genes in Haloferax volcanii are essential for viability when grown aerobically in
      complex medium. This represents the first report of an organism that requires the
      Tat pathway for viability when grown under such conditions. Deletion of the
      nonessential gene had no effect on the secretion of a verified substrate of the
      Tat pathway. The two TatA paralogs TatAo and TatAt were detected in both the
      membrane and cytoplasm and could be copurified from the latter fraction. Using
      size exclusion chromatography to further characterize cytoplasmic and membrane
      TatA proteins, we find these proteins present in high-molecular-weight complexes
      in both cellular fractions.

PMID- 16291685
TI  - Isolation and characterization of new thiamine-deregulated mutants of Bacillus
      subtilis.
AB  - In bacteria, thiamine pyrophosphate (TPP) is an essential cofactor that is
      synthesized de novo. Thiamine, however, is not an intermediate in the
      biosynthetic pathway but is salvaged from the environment and phosphorylated to
      TPP. We have isolated and characterized new mutants of Bacillus subtilis that
      deregulate thiamine biosynthesis and affect the export of thiamine products from
      the cell. Deletion of the ydiA gene, which shows significant similarity to the
      thiamine monophosphate kinase gene of Escherichia coli (thiL), did not generate
      the expected thiamine auxotroph but instead generated a thiamine bradytroph that
      grew to near-wild-type levels on minimal medium. From this DeltathiL deletion
      mutant, two additional ethyl methanesulfonate-induced mutants that derepressed
      the expression of a thiC-lacZ transcriptional reporter were isolated. One mutant,
      Tx1, contained a nonsense mutation within the B. subtilis yloS (thiN) gene that
      encodes a thiamine pyrophosphokinase, a result which confirmed that B. subtilis
      contains a single-step, yeast-like thiamine-to-TPP pathway in addition to the
      bacterial TPP de novo pathway. A second mutant, strain Tx26, was shown to contain
      two lesions. Genetic mapping and DNA sequencing indicated that the first mutation
      affected yuaJ, which encodes a thiamine permease. The second mutation was located
      within the ykoD cistron of the ykoFEDC operon, which putatively encodes the
      ATPase component of a unique thiamine-related ABC transporter. Genetic and
      microarray studies indicated that both the mutant yuaJ and ykoD genes were
      required for the derepression of thiamine-regulated genes. Moreover, the
      combination of the four mutations (the DeltathiL, thiN, yuaJ, and ykoD mutations)
      into a single strain significantly increased the production and excretion of
      thiamine products into the culture medium. These results are consistent with the
      proposed "riboswitch" mechanism of thiamine gene regulation (W. C. Winkler, A.
      Nahvi, and R. R. Breaker, Nature 419:952-956, 2002).

PMID- 16291684
TI  - Characterization of temporal protein production in Pseudomonas aeruginosa
      biofilms.
AB  - Phenotypic and genetic evidence supporting the notion of biofilm formation as a
      developmental process is growing. In the present work, we provide additional
      support for this hypothesis by identifying the onset of accumulation of biofilm
      stage specific proteins during Pseudomonas aeruginosa biofilm maturation and by
      tracking the abundance of these proteins in planktonic and three biofilm
      developmental stages. The onset of protein production was found to correlate with
      the progression of biofilms in developmental stages. Protein identification
      revealed that proteins with similar function grouped within similar protein
      abundance patterns. Metabolic and housekeeping proteins were found to group
      within a pattern separate from virulence, antibiotic resistance, and quorum
      sensing-related proteins. The latter were produced in a progressive manner,
      indicating that attendant features that are characteristic of biofilms such as
      antibiotic resistance and virulence may be part of the biofilm developmental
      process. Mutations in genes for selected proteins from several protein production
      patterns were made, and the impact of these mutations on biofilm development was
      evaluated. The proteins cytochrome c oxidase, a probable chemotaxis transducer, a
      two-component response regulator, and MexH were produced only in mature and late
      stage biofilms. Mutations in the genes encoding these proteins did not confer
      defects in growth, initial attachment, early biofilm formation, or twitching
      motility but were observed to arrest biofilm development at the stage of cell
      cluster formation we call the maturation-1 stage. The results indicated that
      expression of theses genes was required for the progression of biofilms into
      three-dimensional structures on abiotic surfaces and the completion of the
      biofilm developmental cycle. Reverse transcription-PCR analysis confirmed the
      detectable change in expression of the respective genes ccoO, PA4101, and PA4208.
      We propose a possible mechanism for the role of these biofilm-specific proteins
      in biofilm formation.

PMID- 16291686
TI  - Homodimeric hexaprenyl pyrophosphate synthase from the thermoacidophilic
      crenarchaeon Sulfolobus solfataricus displays asymmetric subunit structures.
AB  - Hexaprenyl pyrophosphate synthase (HexPPs) from Sulfolobus solfataricus catalyzes
      the synthesis of trans-C(30)-hexaprenyl pyrophosphate (HexPP) by reacting two
      isopentenyl pyrophosphate molecules with one geranylgeranyl pyrophosphate. The
      crystal structure of the homodimeric C(30)-HexPPs resembles those of other trans
      prenyltransferases, including farnesyl pyrophosphate synthase (FPPs) and
      octaprenyl pyrophosphate synthase (OPPs). In both subunits, 10 core helices are
      arranged about a central active site cavity. Leu164 in the middle of the cavity
      controls the product chain length. Two protein conformers are observed in the S.
      solfataricus HexPPs structure, and the major difference between them occurs in
      the flexible region of residues 84 to 100. Several helices (alphaI, alphaJ,
      alphaK, and part of alphaH) and the associated loops have high-temperature
      factors in one monomer, which may be related to the domain motion that controls
      the entrance to the active site. Different side chain conformations of Trp136 in
      two HexPPs subunits result in weaker hydrophobic interactions at the dimer
      interface, in contrast to the symmetric pi-pi stacking interactions of aromatic
      side chains found in FPPs and OPPs. Finally, the three-conformer switched model
      may explain the catalytic process for HexPPs.

PMID- 16291687
TI  - Biosynthesis of hexahydroxyperylenequinone melanin via oxidative aryl coupling by
      cytochrome P-450 in Streptomyces griseus.
AB  - Dihydroxyphenylalanine (DOPA) melanins formed from tyrosine by tyrosinases are
      found in microorganisms, plants, and animals. Most species in the soil-dwelling,
      gram-positive bacterial genus Streptomyces produce DOPA melanins and
      melanogenesis is one of the characteristics used for taxonomy. Here we report a
      novel melanin biosynthetic pathway involving a type III polyketide synthase
      (PKS), RppA, and a cytochrome P-450 enzyme, P-450mel, in Streptomyces griseus. In
      vitro reconstitution of the P-450mel catalyst with spinach ferredoxin-NADP(+)
      reductase/ferredoxin revealed that it catalyzed oxidative biaryl coupling of
      1,3,6,8-tetrahydroxynaphthalene (THN), which was formed from five molecules of
      malonyl-coenzyme A by the action of RppA to yield 1,4,6,7,9,12
      hexahydroxyperylene-3,10-quinone (HPQ). HPQ readily autopolymerized to generate
      HPQ melanin. Disruption of either the chromosomal rppA or P-450mel gene resulted
      in abolishment of the HPQ melanin synthesis in S. griseus and a decrease in the
      resistance of spores to UV-light irradiation. These findings show that THN
      derived melanins are not exclusive in eukaryotic fungal genera but an analogous
      pathway is conserved in prokaryotic streptomycete species as well. A vivid
      contrast in THN melanin biosynthesis between streptomycetes and fungi is that the
      THN synthesized by the action of a type III PKS is used directly for condensation
      in the former, while the THN synthesized by the action of type I PKSs is first
      reduced and the resultant 1,8-dihydroxynaphthalene is then condensed in the
      latter.

PMID- 16291688
TI  - Structural basis for shikimate-binding specificity of Helicobacter pylori
      shikimate kinase.
AB  - Shikimate kinase (EC 2.7.1.71) catalyzes the specific phosphorylation of the 3
      hydroxyl group of shikimic acid in the presence of ATP. As the fifth key step in
      the shikimate pathway for aromatic amino acid biosynthesis in bacteria, fungi,
      and plants, but not mammals, shikimate kinase represents an attractive target for
      the development of new antimicrobial agents, herbicides, and antiparasitic
      agents. Here, we report the 1.8-Angstroms crystal structure of Helicobacter
      pylori shikimate kinase (HpSK). The crystal structure shows a three-layer
      alpha/beta fold consisting of a central sheet of five parallel beta-strands
      flanked by seven alpha-helices. An HpSK-shikimate-PO(4) complex was also
      determined and refined to 2.3 Angstroms, revealing induced-fit movement from an
      open to a closed form on substrate binding. Shikimate is located above a short
      3(10) helix formed by a strictly conserved motif (GGGXV) after beta(3). Moreover,
      several highly conserved charged residues including Asp33 (in a conserved DT/SD
      motif), Arg57, and Arg132 (interacting with shikimate) are identified, guiding
      the development of novel inhibitors of shikimate kinase.

PMID- 16291689
TI  - A degenerate type III secretion system from septicemic Escherichia coli
      contributes to pathogenesis.
AB  - The type III secretion system (T3SS) is an important virulence factor used by
      several gram-negative bacteria to deliver effector proteins which subvert host
      cellular processes. Enterohemorrhagic Escherichia coli O157 has a well-defined
      T3SS involved in attachment and effacement (ETT1) and critical for virulence. A
      gene cluster potentially encoding an additional T3SS (ETT2), which resembles the
      SPI-1 system in Salmonella enterica, was found in its genome sequence. The ETT2
      gene cluster has since been found in many E. coli strains, but its in vivo role
      is not known. Many of the ETT2 gene clusters carry mutations and deletions,
      raising the possibility that they are not functional. Here we show the existence
      in septicemic E. coli strains of an ETT2 gene cluster, ETT2(sepsis), which,
      although degenerate, contributes to pathogenesis. ETT2(sepsis) has several
      premature stop codons and a large (5 kb) deletion, which is conserved in 11 E.
      coli strains from cases of septicemia and newborn meningitis. A null mutant
      constructed to remove genes coding for the putative inner membrane ring of the
      secretion complex exhibited significantly reduced virulence. These results are
      the first demonstration of the importance of ETT2 for pathogenesis.

PMID- 16291690
TI  - Proteomic characterization of Yersinia pestis virulence.
AB  - The Yersinia pestis proteome was studied as a function of temperature and calcium
      by two-dimensional differential gel electrophoresis. Over 4,100 individual
      protein spots were detected, of which hundreds were differentially expressed. A
      total of 43 differentially expressed protein spots, representing 24 unique
      proteins, were identified by mass spectrometry. Differences in expression were
      observed for several virulence-associated factors, including catalase-peroxidase
      (KatY), murine toxin (Ymt), plasminogen activator (Pla), and F1 capsule antigen
      (Caf1), as well as several putative virulence factors and membrane-bound and
      metabolic proteins. Differentially expressed proteins not previously reported to
      contribute to virulence are candidates for more detailed mechanistic studies,
      representing potential new virulence determinants.

PMID- 16291691
TI  - CspA regulates pigment production in Staphylococcus aureus through a SigB
      dependent mechanism.
AB  - We report that the cold shock protein CspA of Staphylococcus aureus is required
      for maximal production of pigment. Results from transcriptional studies revealed
      that loss of CspA resulted in decreased expression of genes needed for the
      biosynthesis of 4,4'-diaponeurosporene and the alternative sigma factor SigB.

PMID- 16291692
TI  - The Pseudomonas aeruginosa proteome during anaerobic growth.
AB  - Isotope-coded affinity tag analysis and two-dimensional gel electrophoresis
      followed by tandem mass spectrometry were used to identify Pseudomonas aeruginosa
      proteins expressed during anaerobic growth. Out of the 617 proteins identified,
      158 were changed in abundance during anaerobic growth compared to during aerobic
      growth, including proteins whose increased expression was expected based on their
      role in anaerobic metabolism. These results form the basis for future analyses of
      alterations in bacterial protein content during growth in various environments,
      including the cystic fibrosis airway.

PMID- 16291693
TI  - Four unusual two-component signal transduction homologs, RedC to RedF, are
      necessary for timely development in Myxococcus xanthus.
AB  - We identified a cluster of four two-component signal transduction genes that are
      necessary for proper progression of Myxococcus xanthus through development. redC
      to redF mutants developed and sporulated early, resulting in small, numerous, and
      disorganized fruiting bodies. Yeast two-hybrid analyses suggest that RedCDEF act
      in a single signaling pathway. The previously identified espA gene displays a
      phenotype similar to that of redCDEF. However, combined mutants defective in espA
      redCDEF exhibited a striking additive developmental phenotype, suggesting that
      EspA and RedC to RedF play independent roles in controlling developmental
      progression.

PMID- 16291694
TI  - New class of competitive inhibitor of bacterial histidine kinases.
AB  - Bacterial histidine kinases have been proposed as targets for the discovery of
      new antibiotics, yet few specific inhibitors of bacterial histidine kinases have
      been reported. We report here a novel thienopyridine (TEP) compound that inhibits
      bacterial histidine kinases competitively with respect to ATP but does not
      comparably inhibit mammalian serine/threonine kinases. Although it partitions
      into membranes and does not inhibit the growth of bacterial or mammalian cells,
      TEP could serve as a starting compound for a new class of histidine kinase
      inhibitors with antibacterial activity.

PMID- 16291695
TI  - A second case of -1 ribosomal frameshifting affecting a major virion protein of
      the Lactobacillus bacteriophage A2.
AB  - The bacteriophage A2 major tail protein gene utilizes a -1 translational
      frameshift to generate two structural polypeptides. Frameshifting is promoted by
      a slippery sequence and an RNA pseudoknot located 3' of the gene. The major head
      gene presents a similar recoding ability. A2 is the only phage described with two
      -1 frameshifts.

PMID- 16291696
TI  - Vancomycin stress response in a sensitive and a tolerant strain of Streptococcus
      pneumoniae.
AB  - The vancomycin stress response was studied in Streptococcus pneumoniae strains T4
      (TIGR4) and Tupelo. Vancomycin affected the expression of 175 genes, including
      genes encoding transport functions and enzymes involved in aminosugar metabolism.
      The two-component systems TCS03, TCS11, and CiaRH also responded to antibiotic
      treatment. We hypothesize that the three regulons are an important part of the
      bacterium's response to vancomycin stress.

PMID- 16291697
TI  - Iron-responsive regulation of biofilm formation in staphylococcus aureus involves
      fur-dependent and fur-independent mechanisms.
AB  - We have shown that Staphylococcus aureus biofilm production is induced in iron
      restricted conditions and is repressed by iron via a Fur-independent mechanism,
      while Fur has both positive and negative regulatory roles in low iron.
      Furthermore, there is no significant increase in polymeric N-acetylglucosamine
      polysaccharide expression to account for induction of biofilms in low iron.

PMID- 16291698
TI  - Identification of regions involved in enzymatic stability of peptide deformylase
      of Mycobacterium tuberculosis.
AB  - Sequence analysis of peptide deformylase of Mycobacterium tuberculosis revealed
      the presence of insertions (residues 74 to 85) and an unusually long carboxy
      terminal end (residues 182 to 197). Our results with deletion mutants indicated
      the contribution of these regions in maintaining enzymatic stability.
      Furthermore, we showed that the region spanning the insertions was responsible
      for maintaining resistance to oxidizing agents, like H(2)O(2).

PMID- 16291699
TI  - The cell cycle-apoptosis connection revisited in the adult brain.
AB  - Adult neurogenesis is studied in vivo using thymidine analogues such as
      bromodeoxyuridine (BrdU) to label DNA synthesis during the S phase of the cell
      cycle. However, BrdU may also label DNA synthesis events not directly related to
      cell proliferation, such as DNA repair and/or abortive reentry into the cell
      cycle, which can occur as part of an apoptotic process in postmitotic neurons. In
      this study, we used three well-characterized models of injury-induced neuronal
      apoptosis and the combined visualization of cell birth (BrdU labeling) and death
      (Tdt-mediated dUTP-biotin nick end labeling) to investigate the specificity of
      BrdU incorporation in the adult mouse brain in vivo. We present evidence that
      BrdU is not significantly incorporated during DNA repair and that labeling is not
      detected in vulnerable or dying postmitotic neurons, even when a high dose of
      BrdU is directly infused into the brain. These findings have important
      implications for a controversy surrounding adult neurogenesis: the connection
      between cell cycle reactivation and apoptosis of terminally differentiated
      neurons.

PMID- 16291700
TI  - REVIEW: Efficacy and mechanisms of action of statins in the treatment of diabetic
      dyslipidemia.
AB  - CONTEXT: The Adult Treatment Panel III recommends 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitors, or statins, as first-line lipid-altering therapy
      for all adult patients with diabetes mellitus. This is based on the well
      characterized efficacy and safety profiles of this class of agents as well as
      several clinical trials demonstrating that statin treatment reduces the risk of
      cardiovascular events. EVIDENCE ACQUISITION: This review provides an overview of
      the effectiveness and mechanisms of action of statins in patients with diabetes
      mellitus using small efficacy trials and large clinical outcomes trials as well
      as studies of the effects of statins on apolipoprotein B (apoB) metabolism.
      EVIDENCE SYNTHESIS: The major findings presented are a review of mechanistic
      studies of selected subjects with diabetes mellitus and dyslipidemia and a
      compilation of results from large-scale clinical trials of patients with
      diabetes. CONCLUSIONS: Statins are highly efficacious as low-density lipoprotein
      cholesterol-lowering agents and have more modest effects on very low-density
      lipoprotein triglyceride and high-density lipoprotein cholesterol levels. The
      effects of statins on plasma lipids and lipoproteins result from their ability to
      both increase the efficiency with which very low-density lipoprotein and low
      density lipoprotein are cleared from the circulation and reduce the production of
      apoB-containing lipoproteins by the liver. Additional investigations are needed
      to clarify the mechanisms by which statins reduce apoB secretion from the liver.

PMID- 16291701
TI  - Pamidronate in children with osteogenesis imperfecta: histomorphometric effects
      of long-term therapy.
AB  - CONTEXT: Intravenous pamidronate treatment is beneficial to children and
      adolescents with osteogenesis imperfecta (OI), but the effects of prolonged
      therapy are not well characterized. OBJECTIVE: The objective of this study was to
      assess the effect of long-term pamidronate treatment on the bone tissue of
      children and adolescents with OI. DESIGN: This is an observational study on OI
      patients receiving iv pamidronate for more than 4 yr. SETTING: The study was
      carried out in a pediatric metabolic bone research unit. PATIENTS: Patients were
      25 moderately to severely affected OI patients (seven girls) aged 1.4-15.3 yr at
      baseline. INTERVENTION: Intervention was cyclical iv pamidronate at a dose of 9
      mg/kg.yr. MAIN OUTCOME MEASURES: Iliac bone biopsy and lumbar spine bone mineral
      density measures were obtained at treatment start, after 2.7 +/- 0.5 yr (mean +/-
      sd), and after 5.5 +/- 0.7 yr of therapy. RESULTS: Average areal bone mineral
      density increased by 72% in the first half of the observation period, but by only
      24% in the second half. Mean cortical width and cancellous bone volume increased
      by 87 and 38%, respectively, between baseline and the first time point during
      treatment (P < 0.001 for all changes). Thereafter, cortical width did not change
      significantly, but there was a trend (P = 0.06) toward higher cancellous bone
      volume. Average bone formation rate on trabecular surfaces decreased by 70% after
      pamidronate treatment was initiated and showed a trend (P = 0.08) toward a
      further decline in the second part of the study interval. CONCLUSION: The gains
      that can be achieved with pamidronate treatment appear to be largely realized in
      the first 2-4 yr.

PMID- 16291702
TI  - Growth hormone (GH) pharmacogenetics: influence of GH receptor exon 3 retention
      or deletion on first-year growth response and final height in patients with
      severe GH deficiency.
AB  - CONTEXT: A polymorphism in GHR gene, the presence or absence of exon 3, has been
      shown to influence the 1- and 2-yr growth responses to human recombinant GH (hGH)
      therapy in children without GH deficiency (GHD). OBJECTIVE: The objective of this
      study was to assess the influence of GHR-exon-3 genotype on the short and long
      term response to hGH therapy in children with GHD. SETTING: The study was
      conducted in the university hospital. DESIGN AND PATIENTS: Genotype and
      retrospective analysis was performed on data of 75 children with GHD.
      INTERVENTION: INTERVENTION consisted of hGH treatment at a mean dose of 33
      mug/kg.d and GHR-exon-3 genotype by multiplex PCR. MAIN OUTCOME MEASURES: The
      main outcome measures were GHR genotype: full-length (fl) and exon 3-deleted (d3)
      alleles, growth velocity in 58 children who remained prepubertal during the first
      year, and adult height in 44 patients with GHD after 7.5 +/- 3.0 yr of treatment.
      RESULTS: Clinical and laboratory data at the start of treatment and hGH doses
      were indistinguishable among patients with different GHR-exon-3 genotypes (fl/fl
      vs. fl/d3 or d3/d3). Patients carrying at least one GHRd3 allele had a
      significantly better growth velocity in the first year of hGH replacement (12.3
      +/- 2.6 vs. 10.6 +/- 2.3 cm/yr; P < 0.05) and achieved a taller adult height
      (final height sd score, -0.8 +/- 1.1 vs. -1.7 +/- 1.2; P < 0.05) when compared
      with patients homozygous for GHRfl alleles. CONCLUSIONS: Patients with GHD who
      are homozygous for GHR exon 3 fl were less responsive to short- and long-term hGH
      therapy. Approximately half of the population is homozygous for GHRfl, and future
      studies adjusting hGH therapy to genotype may improve outcome.

PMID- 16291703
TI  - Gestational age-dependent up-regulation of prostaglandin D synthase (PGDS) and
      production of PGDS-derived antiinflammatory prostaglandins in human placenta.
AB  - CONTEXT: The importance of prostaglandin (PG) signaling pathways to the
      maintenance of pregnancy and initiation of labor is well recognized. However, the
      complexity of these pathways and the mechanism(s) of their coordinated regulation
      in physiological and pathological conditions are only now being appreciated.
      OBJECTIVES: In this report we provide new evidence of a complete pathway for the
      biosynthesis and actions of PGD(2) and its metabolites within human gestational
      tissues. MATERIALS AND METHODS: Using immunohistochemistry and Northern and
      Western blotting, we demonstrate the dynamic regulation of H-type PGD synthase
      (PGDS) in placenta during gestation; in contrast, L-type PGDS and its PG products
      were detected in amniotic fluid, with increased amounts associated with labor.
      RESULTS: Placental tissues were shown to express both forms of the PGD(2)
      receptor identified to date, D prostanoid(1) (DP(1)) and DP(2)/chemotactic
      receptor on type 2 helper T cells, with a distribution consistent with the
      villous placenta being a major target, as well as source, of PGD(2). In vitro,
      placental PGD(2) production was shown to be stimulated upon inflammatory
      activation, whereas PGD(2) and its J series metabolites exerted potent inhibitory
      effects on placental cytokine production. CONCLUSIONS: These findings suggest
      that PGDS-derived prostanoids play important physiological roles in the placenta,
      such as immunoregulation and feto-placental communication, while potentially
      having a regulatory role in the processes of parturition.

PMID- 16291704
TI  - Prevalence and characteristics of the metabolic syndrome in primary
      aldosteronism.
AB  - CONTEXT: Patients with hypertension have a high prevalence of concurrent
      metabolic abnormalities, including obesity, dyslipidemia, and hyperglycemia.
      Clustering of these cardiovascular risk factors, defined as metabolic syndrome,
      causes a more pronounced target organ damage. Aldosterone excess has been found
      to be associated with glucose disorders and may contribute to cardiovascular
      damage. OBJECTIVE: The aim of our study was to assess the prevalence and the
      characteristics of the metabolic syndrome in a group of patients with
      hypertension due to primary aldosteronism compared with patients with essential
      hypertension. METHODS: The National Cholesterol Education Program Adult Treatment
      Panel III definition of the metabolic syndrome was used. Eighty-five patients
      with primary aldosteronism and 381 patients with essential hypertension were
      studied. Most patients were not receiving antihypertensive therapy during the
      investigation. RESULTS: Blood glucose and systolic blood pressure were higher (P
      < 0.05 and P < 0.01, respectively) and duration of hypertension was longer (P <
      0.05) in primary aldosteronism than in essential hypertension. The prevalence of
      metabolic syndrome was higher in primary aldosteronism than in essential
      hypertension (41.1% vs. 29.6%; P < 0.05). Distribution of single components of
      the metabolic syndrome other than hypertension showed a higher prevalence of
      hyperglycemia in primary aldosteronism than in essential hypertension (27.0% vs.
      15.2%; P < 0.05). CONCLUSIONS: Our findings confirm a negative effect of
      aldosterone excess on glucose metabolism and suggest that the recently reported
      higher rates of cardiovascular events in primary aldosteronism than in essential
      hypertension might be due to increased prevalence of the metabolic syndrome in
      the former condition.

PMID- 16291705
TI  - Characterization of insulin secretion and resistance in type 2 diabetes of
      adolescents.
AB  - CONTEXT: Type 2 diabetes (T2D) in obese children is an emerging problem,
      including in Europe. Its presentation at diagnosis very often differs from that
      in adults. OBJECTIVE: The objective of this study was to investigate the relative
      contributions of the two components of T2D, insulin resistance and insulin
      secretion, early in the history of the disease in adolescents. PATIENTS AND
      METHODS: Six obese adolescents with T2D were included 2 months to 4.3 yr after
      diagnosis (five girls and one boy; median age, 15.4 yr; median body mass index,
      4.4 sd). Peripheral and hepatic insulin sensitivity was evaluated with euglycemic
      hyperinsulinemic (40 mU/m(2).min) clamp. First-phase insulin release was
      evaluated after iv glucose stimulation. A graded iv glucose infusion and an
      arginine test were performed to measure insulin secretion. RESULTS: All patients
      showed decreased peripheral glucose uptake to the same extent. Five patients
      showed hepatic insulin resistance. First-phase insulin release was very low in
      two patients. Three patients showed an exaggerated insulin response under graded
      glucose infusion and preserved secretion under arginine stimulation. Three other
      patients, with elevated fasting plasma glucose levels, demonstrated a very low
      insulin response under glucose stimulation and a low insulin response under
      arginine stimulation. CONCLUSIONS: These data emphasize that together with marked
      insulin resistance, the failure of beta-cell function is a major component in the
      course of T2D in childhood.

PMID- 16291706
TI  - The d3-growth hormone (GH) receptor polymorphism is associated with increased
      responsiveness to GH in Turner syndrome and short small-for-gestational-age
      children.
AB  - CONTEXT: A protein polymorphism of the GH receptor (GHR) based on the genomic
      deletion of exon 3 (d3-GHR) has recently been linked to the magnitude of growth
      response to high-dose recombinant human GH (rhGH) therapy of short children
      without GH deficiency. OBJECTIVE: This study tests the novel association in two
      distinct groups of rhGH-treated patients, short girls with Turner syndrome and
      short children born small for gestational age (SGA). DESIGN: The retrospective
      study included all children who were treated with rhGH during the last 18 yr at
      our hospital. PATIENTS: Patients with Turner syndrome were defined by the
      specific karyotype (n = 53), short children born SGA were determined by birth
      length and/or weight less than -2.0 sd score and a height at start of rhGH
      therapy less than -2.0 sd score (n = 60). Exclusion criteria were puberty, an age
      less than 3.5 or more than 14 yr, and GH deficiency. MATERIALS AND METHODS:
      Growth prediction for the first year of therapy was calculated on the basis of
      rhGH dose, age, weight, height, and gender-adjusted midparental height according
      to the prediction models by Ranke et al. The GHR-exon 3 locus was genotyped using
      a PCR multiplex assay. GH, IGF-I, and IGF binding protein 3 (IGFBP-3) were
      measured by RIA. INTERVENTION: For growth promotion, a mean rhGH dose of 38
      mug/kg.d (sd, +/-8) was administered in Turner syndrome patients and 56 mug/kg.d
      (sd, +/-11) in short children born SGA. RESULTS: No significant difference in
      height, spontaneous height velocity, IGF-I, and IGFBP-3 levels was found at the
      start of rhGH therapy in the three GHR genotype groups studied. At the first year
      of treatment, girls with Turner syndrome carrying one or two d3-GHR alleles
      showed a significantly higher increment in height velocity (P = 0.019) and
      exceeded their growth prediction significantly (P = 0.007), whereas their
      increments of IGF-I and IGFBP-3, weight, and height were not significantly
      different. Carriers of d3-GHR in the group of short children born SGA grew
      significantly faster than predicted (P = 0.023). However, in comparison to the
      carriers of full-length GHR, gain of height velocity was not significantly higher
      (P = 0.067). The mean gain of height associated with d3-GHR accounted for
      approximately 0.75 cm in SGA and 1.5 cm in Turner syndrome during the first year
      of rhGH therapy. CONCLUSIONS: Our data support the theory that there is increased
      responsiveness to high-dose rhGH in association with the d3-GHR genotype. The
      magnitude of this effect may depend on the primary origin of the short stature.

PMID- 16291707
TI  - Genetic and nongenetic determinants of skeletal muscle glucose transporter 4
      messenger ribonucleic acid levels and insulin action in twins.
AB  - CONTEXT: Insulin-stimulated glucose uptake in skeletal muscle is mediated through
      translocation of the insulin-sensitive glucose transporter 4 (GLUT4)-containing
      vesicles to the plasma membrane. Thus, skeletal muscle GLUT4 content plays an
      important role in whole-body insulin sensitivity. OBJECTIVES: The objectives of
      this study were 1) to examine the relative impact of genetic vs. environmental
      factors on skeletal muscle GLUT4 mRNA expression using biometric modeling, and 2)
      to identify factors influencing the expression of GLUT4 and insulin-stimulated
      whole-body metabolism. DESIGN: We measured GLUT4 mRNA expression in biopsies from
      young and elderly monozygotic (MZ) and dizygotic (DZ) twins before and during a 2
      h hyperinsulinemic euglycemic clamp including 3-(3)H-tritiated glucose and
      indirect calorimetry. PARTICIPANTS: A random sample of young (22-31 yr; n = 89)
      and elderly (57-66 yr; n = 69) same sex MZ and DZ twin pairs identified through
      the Danish Twin Register were studied. RESULTS: We found a major genetic
      component in the control of basal and insulin-stimulated GLUT4 mRNA expression in
      young and elderly twins. GLUT4 gene expression increased upon insulin stimulation
      in both young and elderly twins. Multiple regression analysis revealed that both
      basal and insulin-stimulated GLUT4 mRNA expressions were positively related to
      birth weight and total body aerobic capacity and were higher in MZ vs. DZ twins
      as well as in males vs. females. Both basal and insulin-stimulated expressions of
      GLUT4 were independently and significantly related to whole-body in vivo insulin
      action, nonoxidative glucose metabolism, and glucose oxidation. CONCLUSION: We
      show that skeletal muscle GLUT4 gene expression in twins is significantly and
      independently related to glucose metabolism and is determined by both genetic and
      nongenetic factors, including zygosity and birth weight.

PMID- 16291708
TI  - Clinical trials in amyotrophic lateral sclerosis: the tenuous past and the
      promising future.
AB  - The past decade of research in amyotrophic lateral sclerosis has contributed to a
      greater understanding of the disease process, the development of relevant animal
      models, and the identification of several therapeutic approaches that may delay
      disease progression. Completed and ongoing clinical trials and the process of
      selecting drugs for clinical trials are presented.

PMID- 16291709
TI  - Danshen: an overview of its chemistry, pharmacology, pharmacokinetics, and
      clinical use.
AB  - Danshen, the dried root of Salvia miltiorrhiza, has been widely used in China
      and, to a lesser extent, in Japan, the United States, and other European
      countries for the treatment of cardiovascular and cerebrovascular diseases. In
      China, the specific clinical use is angina pectoris, hyperlipidemia, and acute
      ischemic stroke. The current review covers its traditional uses, chemical
      constituents, pharmacological activities, pharmacokinetics, clinical
      applications, and potential herb-drug interactions based on information obtained
      in both the English and Chinese literature. Although numerous clinical trials
      have demonstrated that certain Danshen products in China are effective and safe
      for the treatment of cardiovascular diseases, most of these lack sufficient
      quality. Therefore, large randomized clinical trials and further scientific
      research to determine its mechanism of actions will be necessary to ensure the
      safety, effectiveness, and better understanding of its action.

PMID- 16291710
TI  - Drug-drug and drug-food interactions between tenofovir disoproxil fumarate and
      didanosine.
AB  - The drug-drug and drug-food interactions between tenofovir DF and didanosine EC
      were evaluated in 2 pharmacokinetic studies in healthy adult subjects. When 400
      mg was dosed with tenofovir DF, mean didanosine AUC was increased by 44% to 60%
      following fasted or fed administration. Staggered coadministration (2 hour,
      fasted) of a reduced didanosine dose of 250 mg resulted in equivalent didanosine
      exposure, while simultaneous administration with tenofovir DF in the fasted and
      fed state resulted in didanosine AUCs similar to that of the reference treatment
      of 400 mg alone in the fasted state. These data indicate that a dose reduction of
      didanosine is warranted when it is used with tenofovir DF. The drug-drug-food
      interaction of didanosine may offer more flexible dosing of didanosine EC when it
      is used with tenofovir DF. Patients receiving tenofovir DF and didanosine
      together should be carefully monitored for safety and efficacy.

PMID- 16291711
TI  - Pharmacokinetics of sirolimus (rapamycin) in subjects with mild to moderate
      hepatic impairment.
AB  - Eighteen adult subjects with mild to moderate hepatic impairment and 18 healthy
      control subjects were given a single 15-mg dose of sirolimus by oral solution.
      Mean whole-blood sirolimus weight-normalized oral-dose clearances (CL/F) were
      significantly decreased (P = .02) in subjects with mild to moderate hepatic
      impairment by -31.8% and -36.0%, respectively, compared with controls. There were
      no significant differences in mean sirolimus C(max) and t(max) values among
      groups. The observed decreases in CL/F may be relevant in renal transplant
      patients with mild to moderate hepatic impairment, based on the close similarity
      of sirolimus CL/F in controls and previously studied stable renal transplant
      patients receiving multiple-dose administration of sirolimus and cyclosporine.
      There was considerable overlap in the CL/F values of hepatic-impaired subjects
      and controls, suggesting that whole-blood sirolimus trough concentrations in
      renal transplant patients exhibiting mild to moderate hepatic impairment be
      initially monitored to assess the need for dose adjustments.

PMID- 16291712
TI  - Safety and pharmacokinetics of coadministered voriconazole and anidulafungin.
AB  - There is considerable interest in combining echinocandin and triazole antifungal
      agents for treatment of invasive fungal infections; however, information is
      needed regarding the tolerability and potential for pharmacokinetic interactions.
      Anidulafungin is a semisynthetic echinocandin, and voriconazole is an extended
      spectrum triazole. In a random sequence, 17 subjects received anidulafungin with
      placebo, voriconazole with placebo, and anidulafungin with voriconazole.
      Anidulafungin was administered intravenously: 200 mg on day 1, then 100 mg/d on
      days 2 through 4. Voriconazole was administered orally: 400 mg every 12 hours on
      day 1, then 200 mg every 12 hours on days 2 to 4. No dose-limiting toxicities or
      serious adverse events occurred, and all adverse events were mild and consistent
      with the known safety profiles of both drugs. Pharmacokinetic parameters were not
      affected by coadministration. The geometric mean ratio (90% confidence interval)
      of the combination/drug alone for AUC(SS) was 97.4% (94.9-99.9), 97.4% (92.1
      103.0), and 94.4% (87.0-102.5) for anidulafungin, voriconazole, and the
      voriconazole metabolite, respectively.

PMID- 16291713
TI  - Bioavailability and metabolism of prochlorperazine administered via the buccal
      and oral delivery route.
AB  - Prochlorperazine has been accepted as an effective antiemetic for more than 50
      years; however, its therapeutic success has been limited by its low and variable
      absorption and high first-pass metabolism. A buccal dosage form of
      prochlorperazine has been developed. This article discusses 2 clinical studies
      conducted to characterize the single-dose and multiple-dose pharmacokinetics of
      prochlorperazine and its metabolites after buccal administration. The results of
      these studies demonstrate that buccal administration of prochlorperazine produces
      plasma concentrations more than twice as high as an oral tablet, with less than
      half the variability. In addition to the metabolites, N-desmethyl
      prochlorperazine and prochlorperazine sulfoxide, 2 new metabolites,
      prochlorperazine 7-hydroxide and prochlorperazine sulfoxide 4'-N-oxide, were
      identified and quantitated. Exposure to metabolites after the buccal
      prochlorperazine formulation was approximately half that observed after the oral
      tablet. Buccal administration of prochlorperazine, twice daily, should enhance
      the therapeutic role of prochlorperazine in preventing and treating nausea and
      vomiting.

PMID- 16291714
TI  - Effect of application sites and multiple doses on nicotine pharmacokinetics in
      healthy male Japanese smokers following application of the transdermal nicotine
      patch.
AB  - The transdermal nicotine patch, which contains 25 mg nicotine per 30 cm(2), is
      designed to deliver approximately 15 mg nicotine to the blood circulation in 16
      hours of application for the treatment of smoking cessation. It was applied to 3
      different skin sites (upper arm, abdomen, and back) to examine regional
      variations in percutaneous nicotine absorption in a single-dose, 3-period,
      crossover study involving 9 healthy male Japanese smokers. Nicotine
      pharmacokinetics during once-daily application of the transdermal nicotine patch
      for 5 days was also investigated in 10 healthy smokers. There were statistically
      significant effects of application sites on percutaneous nicotine absorption. The
      ratios (90% confidence intervals) of AUC and C(max) for comparison to the upper
      arm were 102% (88, 117%) and 106% (95, 119%) for the back and 75% (65, 87%) and
      75% (66, 84%) for the abdomen, respectively. These suggest that systemic exposure
      after application to the upper arm was greater compared with the abdomen but
      equivalent to the back. Following multiple doses, linear pharmacokinetics and no
      significant accumulation of nicotine concentrations were observed, and steady
      state was reached by day 2. Only mild itching and erythema were observed at the
      application sites. The transdermal nicotine patch was well tolerated in both
      studies.

PMID- 16291715
TI  - The pharmacokinetics of escitalopram after oral and intravenous administration of
      single and multiple doses to healthy subjects.
AB  - The pharmacokinetics of escitalopram (S-citalopram) and its principal metabolite,
      S-demethylcitalopram (S-DCT), were investigated after intravenous and oral
      administration to healthy subjects. After intravenous infusion of escitalopram,
      the mean systemic clearance and volume of distribution were 31 L/h and 1,100 L,
      respectively. After oral administration of single or multiple doses, the
      absorption was relatively fast, with the maximum observed plasma or serum
      concentration (C(max)) attained after 3 to 4 hours. The mean half-lives were 27
      and 33 hours, respectively; steady state was attained within 10 days. The area
      under the plasma or serum concentration time curve from time zero to 24 hours and
      C(max) was both linear and proportional to the dose. The apparent volume of
      distribution was around 20 L/kg. Comparison of the systemic and oral clearance
      implied a high absolute bioavailability. There was no evidence of interconversion
      from S-citalopram to R-citalopram either in plasma or in urine. Concurrent intake
      of food had no effect on the pharmacokinetics of escitalopram or its metabolite.
      All treatments were well tolerated.

PMID- 16291716
TI  - Effect of lasofoxifene on the pharmacokinetics of digoxin in healthy
      postmenopausal women.
AB  - Lasofoxifene is in late-stage development for the prevention and treatment of
      osteoporosis. Digoxin is commonly prescribed for arrhythmias and congestive heart
      failure, has a narrow therapeutic index, and may be coadministered with
      lasofoxifene. This study was conducted to determine the effect of lasofoxifene (4
      mg loading dose on day 11 followed by 0.5 mg/d on days 12-20) on the steady-state
      pharmacokinetics of digoxin (0.25 mg/d on days 1-20) in 12 healthy postmenopausal
      women. On days 10 and 20, blood and urine samples were collected for 24 hours to
      determine digoxin concentrations. The 90% confidence interval (CI) of least
      squares mean ratio for maximum concentration (C(max)) and area under the plasma
      concentration-time curve (AUC) was calculated. Lasofoxifene had no effect on
      digoxin plasma pharmacokinetics with a ratio (90% CI) of 95.4% (84.6%-107%) and
      103% (97.7%-108%) for C(max) and AUC(0-24), respectively. The ratio of the
      percentage of dose eliminated unchanged in urine in 24 hours was 127% (116% to
      142%). Coadministration of lasofoxifene had no effect on the steady state
      pharmacokinetics of digoxin.

PMID- 16291717
TI  - Effect of a triphasic oral contraceptive on drug-metabolizing enzyme activity as
      measured by the validated Cooperstown 5+1 cocktail.
AB  - The effects of a common oral contraceptive preparation on the activity of 7 drug
      metabolizing enzymes were investigated using the validated Cooperstown 5+1
      Cocktail. In a randomized crossover fashion, 10 premenopausal women received
      caffeine, dextromethorphan, omeprazole, intravenous midazolam, and warfarin +
      vitamin K with and without a triphasic oral contraceptive (ethinyl estradiol 35
      microg) and varying doses of daily norgestimate (0.18, 0.215, and 0.25 mg).
      Bioequivalence testing showed nonequivalence in drug versus no-drug treatment on
      the activity of drug-metabolizing enzymes (as reflected by metabolite ratios
      following probe drug administration); the activity of CYP1A2, CYP2C19, and NAT-2
      decreased following the oral contraceptive, whereas the activity of CYP2C9 and
      CYP2D6 increased. No effects on xanthine oxidase or hepatic CYP3A were seen.
      Application of a non-parametric statistical testing approach revealed a
      significant difference only for CYP1A2 and CYP2C19. This triphasic oral
      contraceptive may have a clinically significant effect on the activity of some
      drug-metabolizing enzymes.

PMID- 16291718
TI  - Influence of chronic renal failure on stereoselective metoprolol metabolism in
      hypertensive patients.
AB  - The influence of chronic renal failure on the stereoselective metabolism of rac
      metoprolol was investigated in 15 hypertensive patients, 7 of them with chronic
      renal failure and 8 with normal renal function. They were treated with rac
      metoprolol (200 mg) for 7 days. The patients of both groups presented
      stereoselectivity in metoprolol metabolism, favoring the formation of 1'R-alpha
      hydroxymetoprolol (AUC(1(')R/1(')S)(0-24) approximately 2.5) and (R)-metoprolol
      acidic metabolite (AUC((S)/(R))(0-24) = 0.8), the latter resulting in the plasma
      accumulation of (S)-metoprolol (AUC((S)/(R))(0-24) = 1.2). Patients with chronic
      renal failure presented plasma accumulation of the 4 alpha-hydroxymetoprolol
      isomers and of both metoprolol acidic metabolite enantiomers. A 50% reduction in
      Cl(R) does not explain the 3- to 4-fold plasma accumulation of metoprolol acidic
      metabolite in this group, suggesting that other pathways of metoprolol
      elimination are affected in chronic renal failure in addition to renal excretion.
      Chronic renal failure does not change the stereoselective kinetic disposition of
      metoprolol but modifies its stereoselective metabolism, inducing some of the CYP
      enzymes involved in the formation of the metoprolol acid metabolite.

PMID- 16291719
TI  - Alfentanil-induced miosis clearance as a liver CYP3A4 and 3A5 activity measure in
      healthy volunteers: improvement of experimental conditions.
AB  - The aims of this study were to demonstrate the correlation between alfentanil
      induced miosis evaluation and alfentanil pharmacokinetics (PK) as a CYP3A4 and
      3A5 activity probe in volunteers and to explain the variability in pupilar
      response and in alfentanil PK. In ambient light, the miosis kinetic parameters
      were significantly correlated with PK (CLs: r = 0.9, P = .00; AUCs: r = 0.8, P =
      .01). In dark, a similar correlation was observed between miosis and alfentanil
      clearances (r = 0.85, P = .03). In 6 volunteers, the sigmoid E(max) model was
      applicable (average E(max) = 2.5 +/- 0.7 mm, gamma = 2.5 +/- 1.6 and EC(50) =
      76.8 +/- 22.3 ng/mL), and in 3, the simple E(max) model was applicable (average
      E(max) = 2.8 +/- 0.3 mm and EC(50) = 19.9 +/- 8.5 ng/mL). There was a large
      interindividual variability in PK parameters (coefficient of variation = 19.7%
      31.2%). Free drug fraction concentrations were negatively correlated with plasma
      alpha(1)-AGP (r = -0.9, P = .04) and albumin levels (r = -0.94, P = .02).
      Alfentanil-induced miosis clearance as a noninvasive CYP3A4 and 3A5 activity
      measure can be done in both ambient and dark conditions. Drug free fraction may
      be responsible for large intersubject variability in alfentanil PK.

PMID- 16291720
TI  - Cytochrome P450 epoxygenases 2C8 and 2C9 are implicated in hypoxia-induced
      endothelial cell migration and angiogenesis.
AB  - Recent studies suggest that cytochrome P450 (CYP) epoxygenase-derived
      epoxyeicosatrienoic acids (EETs) elicit cell proliferation and promote
      angiogenesis. The aim of this study was to determine the role of CYP 2C8/9
      derived EETs in the process of angiogenesis under hypoxic conditions. In human
      endothelial cells, hypoxia enhanced the activity of the CYP 2C9 promoter,
      increased the expression of CYP 2C mRNA and protein and augmented 11,12-EET
      production. In Transwell assays, the migration of endothelial cells pre-exposed
      to hypoxia to increase CYP expression was abolished by CYP 2C antisense
      oligonucleotides as well as by the CYP inhibitor MS-PPOH and the EET antagonist
      14,15-epoxyeicosa-5(Z)-enoic acid (EEZE). Similar findings were obtained in
      porcine coronary artery endothelial cells. CYP 2C9 overexpression in endothelial
      cells increased the association of PAK-1 with Rac, a response also elicited by
      the CYP 2C9 product 11,12-EET. Matrix metalloprotease (MMP) activity was
      increased in CYP-2C9-overexpressing cells and correlated with increased invasion
      through Matrigel-coated Transwell chambers: an effect sensitive to the CYP 2C9
      inhibitor sulfaphenazole as well as to EEZE and the MMP inhibitor GM6001. In in
      vitro angiogenesis models, the EET antagonist inhibited tube formation induced by
      CYP 2C9 overexpression as well as that in endothelial cells exposed to hypoxia to
      increase CYP 2C expression. Furthermore, in the chick chorioallantoic membrane
      assay, EEZE abolished hypoxia-induced angiogenesis. Taken together, these data
      indicate that CYP 2C-derived EETs significantly affect the sequence of angiogenic
      events under hypoxic conditions.

PMID- 16291721
TI  - GPI valence and the fate of secretory membrane proteins in African trypanosomes.
AB  - Progression of GPI-anchored proteins in bloodstream African trypanosomes
      correlates with GPI-valence: homodimeric VSG (2 GPI) is a surface protein;
      heterodimeric transferrin receptor (1 GPI) localizes in the flagellar pocket;
      homodimeric GPI-minus VSG (0 GPI) is rapidly degraded in the lysosome. We test
      this relationship using three native secretory/endocytic proteins as monomeric
      GPI-plus and -minus reporters. GPI-minus procyclin trafficks to the lysosome and
      is degraded. GPI-plus procyclin trafficks to the flagellar pocket/cell surface
      and is released (approximately 50%) with an intact anchor, the remainder
      (approximately 50%) is degraded in the lysosome. GPI-plus BiPNHP, derived from
      the ER marker BiP, is released quantitatively (>80%), while GPI-plus p67HP,
      derived from the lysosomal marker p67, turns over by both release (approximately
      15%) and lysosomal degradation (>50%). Turnover of endogenous transferrin
      receptor occurs primarily by lysosomal degradation (>90%). Thus shedding of
      monovalent GPI reporters correlates inversely with lysosomal targeting. We
      propose that mono-GPI reporters cycle through the flagellar pocket and endosome
      until they are disposed of by either shedding or lysosomal targeting.
      Partitioning between these fates may be a function of individual physical
      properties. Release is likely due to the exclusive use of C-14:0 myristate in the
      bloodstream stage GPI anchor. Up-regulation of transferrin receptor by culture in
      dog serum resulted in prominent cell surface localization, but not in elevated
      release. Surface receptor was non-functional for ligand binding suggesting that
      it may be bivalent homodimers of the GPI-anchored ESAG6 receptor subunit.

PMID- 16291722
TI  - The C. elegans homologs of nephrocystin-1 and nephrocystin-4 are cilia transition
      zone proteins involved in chemosensory perception.
AB  - Nephronophthisis (NPH) is a cystic kidney disorder that causes end-stage renal
      failure in children. Five nephrocystin (nephrocystin-1 to nephrocystin-5) genes,
      whose function is disrupted in NPH patients, have been identified and data
      indicate they form a complex at cell junctions and focal adhesions. More
      recently, the nephrocystin proteins have also been identified in cilia, as have
      multiple other cystic kidney disease related proteins. Significant insights into
      this cilia and cystic kidney disease connection have come from analyses in
      simpler eukaryotic organisms such as Caenorhabditis elegans. In this regard, we
      became interested in the C. elegans homologs of nephrocystin-1 (nph-1) and
      nephrocystin-4 (nph-4) from a database screen to identify genes coordinately
      regulated by the ciliogenic transcription factor DAF-19. Here we show that
      expression of nph-1 and nph-4 is DAF-19 dependent, that their expression is
      restricted to ciliated sensory neurons, and that both NPH-1 and NPH-4 concentrate
      at the transition zones at the base of the cilia, but are not found in the cilium
      axoneme. In addition, NPH-4 is required for the localization of NPH-1 to this
      domain. Interestingly, nph-1 or nph-4 mutants have no obvious cilia assembly
      defects; however, they do have abnormalities in cilia-mediated sensory functions
      as evidenced by abnormal chemotaxis and lifespan regulation. Our data suggest
      that rather than having a ciliogenic role, the NPH proteins play an important
      function as part of the sensory or signaling machinery of this organelle. These
      findings suggest that the defects in human NPH patients may not be the result of
      aberrant ciliogenesis but abnormal cilia-sensory functions.

PMID- 16291723
TI  - Cell wall remodeling at the fission yeast cell division site requires the Rho-GEF
      Rgf3p.
AB  - Cytokinesis in Schizosaccharomyces pombe is accompanied by several stages of cell
      wall remodeling at the division site. Coincident with actomyosin ring
      constriction, primary and secondary septa are deposited and then the primary
      septum is degraded to release daughter cells from one another. These steps
      require the activities of glucan synthases and glucanases, respectively, which
      must be coordinated with one another to prevent cell lysis. The lad1-1 mutation
      undergoes cell lysis specifically at cell division owing to the absence of the
      Rgf3p Rho1-guanine nucleotide exchange factor (GEF) at the division site.
      Electron microscopic analysis indicates that lysis occurs only as the primary
      septum begins to be degraded. Overproduction of either Rho1p or the previously
      uncharacterized Rab-GTPase-activating protein (GAP) involved in secretion,
      Gyp10p, suppresses lad1-1 lethality. Rgf3p is periodically produced in an Ace2p
      dependent manner and localizes to the medial region of the cell early in mitosis,
      a pattern of expression distinct from the highly related Rho-GEF, Rgf1p. Although
      rgf1+ is not an essential gene, it is synthetically lethal with rgf2-deleted
      cells whereas no negative genetic interactions were detected between rgf2-deleted
      cells and lad1-1. Our data suggest that the three closely related fission yeast
      Rho-GEF molecules perform two distinct essential functions. Rgf3p appears
      necessary to stimulate Rho1p-mediated activation of a glucan synthase crucial
      after septation for proper new cell-end formation.

PMID- 16291724
TI  - CEACAM1 functionally interacts with filamin A and exerts a dual role in the
      regulation of cell migration.
AB  - The carcinoembryonic antigen-related cell adhesion molecule CEACAM1 (CD66a) and
      the scaffolding protein filamin A have both been implicated in tumor cell
      migration. In the present study we identified filamin A as a novel binding
      partner for the CEACAM1-L cytoplasmic domain in a yeast two-hybrid screen. Direct
      binding was shown by surface plasmon resonance analysis and by affinity
      precipitation assays. The association was shown for human and rodent CEACAM1-L in
      endogenous CEACAM1-L expressing cells. To address functional aspects of the
      interaction, we used a well-established melanoma cell system. We found in
      different migration studies that the interaction of CEACAM1-L and filamin A
      drastically reduced migration and cell scattering, whereas each of these proteins
      when expressed alone, acted promigratory. CEACAM1-L binding to filamin A reduced
      the interaction of the latter with RalA, a member of the Ras-family of GTPases.
      Furthermore, co-expression of CEACAM1-L and filamin A led to a reduced focal
      adhesion turnover. Independent of the presence of filamin A, the expression of
      CEACAM1-L led to an increased phosphorylation of focal adhesions and to altered
      cytoskeletal rearrangements during monolayer wound healing assays. Together, our
      data demonstrate a novel mechanism for how CEACAM1-L regulates cell migration via
      its interaction with filamin A.

PMID- 16291725
TI  - btn1, the Schizosaccharomyces pombe homologue of the human Batten disease gene
      CLN3, regulates vacuole homeostasis.
AB  - We have cloned the Schizosaccharomyces pombe homologue of the human Batten
      disease gene, CLN3. This gene, btn1, encodes a predicted transmembrane protein
      that is 30% identical and 48% similar to its human counterpart. Cells deleted for
      btn1 were viable but had enlarged and more alkaline vacuoles. Conversely
      overexpression of Btn1p reduced both vacuole diameter and pH. Thus Btn1p
      regulates vacuole homeostasis. The vacuolar defects of btn1Delta cells were
      rescued by heterologous expression of CLN3, proving that Btn1p and CLN3 are
      functional homologues. The disease severity of Batten disease-causing mutations
      (G187A, E295K and V330F), when expressed in btn1 appeared to correlate with their
      effect on vacuolar pH, suggesting that elevated lysosomal pH contributes to the
      disease process. In fission yeast, both Btn1p and CLN3 trafficked to the vacuole
      membrane via early endocytic and pre-vacuolar compartments, and localisation of
      Btn1p to the vacuole membrane was dependent on the Ras GTPase Ypt7p. Importantly,
      vacuoles in cells deleted for both ypt7 and btn1 were larger and more alkaline
      than those of cells deleted for ypt7 alone, indicating that Btn1p has a
      functional role prior to reaching the vacuole. Consistently, btn1 and vma1, the
      gene encoding subunit A of the V1 portion of vATPase, showed conditional
      synthetic lethality, and in cells deleted for vma1 (a subunit of the vacuolar
      ATPase) Btn1p was essential for septum deposition during cytokinesis.

PMID- 16291726
TI  - NO-dependent osteoclast motility: reliance on cGMP-dependent protein kinase I and
      VASP.
AB  - The osteoclast degrades bone in cycles; between cycles, the cell is motile.
      Resorption occurs by acid transport into an extracellular compartment defined by
      an alphavbeta3 integrin ring. NO has been implicated in the regulation of bone
      turnover due to stretch or via estrogen signals, but a specific mechanism linking
      NO to osteoclastic activity has not been described. NO stimulates osteoclast
      motility, and at high concentrations NO causes detachment and terminates
      resorption. Here we demonstrate that NO regulates attachment through the cGMP
      dependent protein kinase I (PKG I) via phosphorylation of the intermediate
      protein VASP. VASP colocalized with the alphavbeta3 ring in stationary cells, but
      alternating bands of VASP and alphavbeta3 occurred when motility was induced by
      NO donors or cGMP. Redistribution of VASP correlated with its phosphorylation.
      Dependency of NO-induced motility on PKG I and on VASP was shown by siRNA
      knockdown of each protein. VASP knockdown also altered distribution of
      alphavbeta3 at the attachment site. We conclude that PKG I and VASP are essential
      for reorganization of attachment and cytoplasmic proteins in motility induced by
      NO or by cGMP.

PMID- 16291727
TI  - Actin at cell-cell junctions is composed of two dynamic and functional
      populations.
AB  - The ability of epithelial cells to polarize requires cell-cell adhesion mediated
      by cadherin receptors. During cell-cell contact, the mechanism via which a flat,
      spread cell shape is changed into a tall, cuboidal epithelial morphology is not
      known. We found that cadherin-dependent adhesion modulates actin dynamics by
      triggering changes in actin organization both locally at junctions and within the
      rest of the cell. Upon induction of cell-cell contacts, two spatial actin
      populations are distinguishable: junctional actin and peripheral thin bundles.
      With time, the relative position of these two populations changes and becomes
      indistinguishable to form a cortical actin ring that is characteristic of mature,
      fully polarized epithelial cells. Junctional actin and thin actin bundles differ
      in their actin dynamics and mechanism of formation, and interestingly, have
      distinct roles during epithelial polarization. Whereas junctional actin
      stabilizes clustered cadherin receptors at cell-cell contacts, contraction of
      peripheral actin bundle is essential for an increase in the maximum height at the
      lateral domain during polarization (cuboidal morphology). Thus, both junctional
      actin and thin bundles are necessary, and cooperate with each other to generate a
      polarized epithelial morphology.

PMID- 16291728
TI  - Modulation of expression of rat mitochondrial 2-oxoglutarate carrier in NRK-52E
      cells alters mitochondrial transport and accumulation of glutathione and
      susceptibility to chemically induced apoptosis.
AB  - We previously showed that two anion carriers of the mitochondrial inner membrane,
      the dicarboxylate carrier (DIC; Slc25a10) and oxoglutarate carrier (OGC;
      Slc25a11), transport glutathione (GSH) from cytoplasm into mitochondrial matrix.
      In the previous study, NRK-52E cells, derived from normal rat kidney proximal
      tubules, were transfected with the wild-type cDNA for the DIC expressed in rat
      kidney; DIC transfectants exhibited increased mitochondrial uptake and
      accumulation of GSH and were markedly protected from chemically induced
      apoptosis. In the present study, cDNAs for both wild-type (WT) and a double
      cysteine mutant of rat OGC (rOGC and rOGC-C221,224S, respectively) were expressed
      in Escherichia coli, purified, and reconstituted into proteoliposomes to assess
      their function. Although both WT rOGC and rOGC-C221,224S exhibited transport
      properties for GSH and 2-oxoglutarate that were similar to those found in
      mitochondria of rat kidney proximal tubules, rates of transport and mitochondrial
      accumulation of substrates were reduced by >75% in rOGC-C221,224S compared with
      the WT carrier. NRK-52E cells were stably transfected with the cDNA for WT-rOGC
      and exhibited 10- to 20-fold higher GSH transport activity than nontransfected
      cells and were markedly protected from apoptosis induced by tert-butyl
      hydroperoxide (tBH) or S-(1,2-dichlorovinyl)-L-cysteine (DCVC). In contrast,
      cells stably transfected with the cDNA for rOGC-C221,224S were not protected from
      tBH- or DCVC-induced apoptosis. These results provide further evidence that
      genetic manipulation of mitochondrial GSH transporter expression alters
      mitochondrial and cellular GSH status, resulting in markedly altered
      susceptibility to chemically induced apoptosis.

PMID- 16291729
TI  - A trimeric anti-HER2/neu ScFv and tumor necrosis factor-alpha fusion protein
      induces HER2/neu signaling and facilitates repair of injured epithelia.
AB  - Tumor necrosis factor (TNF)-alpha genetically fused to the carboxyl terminus of a
      single-chain Fv (ScFv) antibody specific for the human HER2/neu (anti-HER2/neu
      ScFv-TNF-alpha) forms a homotrimeric structure that retains both TNF-alpha
      activity and the ability to bind HER2/neu. In contrast to anti-HER2/neu IgG3,
      anti-HER2/neu ScFv-TNF-alpha induces potent HER2/neu signaling, activating the
      downstream mitogen-activated protein kinase (MAPK) and Akt pathways in SKBR3
      cells. Activation of MAPK and Akt by anti-HER2/neu ScFv-TNF-alpha inhibited the
      apoptosis of SKBR3 cells induced by actinomycin D. Remarkably, anti-HER2/neu ScFv
      TNF-alpha facilitated the repair of injured epithelia. Accelerated wound healing
      required binding to HER2/neu but not TNF-alpha activity since anti-HER2/neu ScFv
      TNF-alpha (S147Y), containing a mutant TNF-alpha with significantly decreased
      biological activity, demonstrated equivalent ability to facilitate wound healing
      and soluble HER2/neu inhibited the effect. These results suggest that trimeric
      anti-HER2/neu ScFv has the potential to facilitate wound healing. In addition,
      fusion with TNF-alpha provides a novel approach to producing polymeric
      antibodies.

PMID- 16291730
TI  - Molecular targeting of BCL2 and BCLXL proteins by synthetic BCL2 homology 3
      domain peptide enhances the efficacy of chemotherapy.
AB  - Chemotherapeutic agents are known to induce programmed cell death or apoptosis.
      The activation of cellular antiapoptotic defense that prevents the translation of
      drug-induced damage into cell death is the key factor in cellular antiapoptotic
      resistance that decreases the chemotherapeutic effectiveness of a broad spectrum
      of anticancer drugs. A novel proapoptotic anticancer drug delivery system (DDS)
      was designed to simultaneously induce apoptosis and suppress antiapoptotic
      cellular defense. The system includes three main components: 1) anticancer drug
      camptothecin (CPT) as an apoptosis inducer, 2) synthetic BCL2 homology 3 domain
      (BH3) peptide as a suppressor of cellular antiapoptotic defense, and 3)
      poly(ethylene glycol) (PEG) polymer as a carrier. The above DDS was studied in
      vitro using A2780 human ovarian carcinoma cells and in vivo on nude mice bearing
      xenografts of human ovarian tumor. The results obtained in both series of
      experiments corroborate each other. They show that the designed DDS provided
      intracellular delivery of active components and suppressed cellular antiapoptotic
      defense, leading to the more pronounced induction of caspase-dependent signaling
      pathway of apoptosis compared with CPT alone and simple CPT-PEG conjugate.
      Including BH3 peptide in complex DDS decreased apoptotic cellular defense,
      substantially increased toxicity of the whole complex, and provided high
      antitumor activity. Therefore, the proposed novel multicomponent proapoptotic
      anticancer drug delivery system has high potential to enhance the efficacy of
      chemotherapy.

PMID- 16291731
TI  - Differential efficacies of somatostatin receptor agonists for G-protein
      activation and desensitization of somatostatin receptor subtype 4-mediated
      responses.
AB  - Although desensitization represents an important physiological feedback mechanism
      that protects against overstimulation, it can significantly limit the therapeutic
      usefulness of drugs. In the current investigation, we have employed Cytosensor
      microphysiometry for the purpose of determining the propensity of somatostatin
      receptor agonists to induce desensitization of the human somatostatin receptor
      subtype 4 (h sst4)-mediated extracellular acidification rate (EAR) response in
      intact Chinese hamster ovary (CHO) cells. We have compared this propensity with
      the efficacies of the agonists as measured in a [35S]guanosine-5'-O-(3
      thio)triphosphate binding assay with membranes of the same CHO-h sst4 cell line.
      We observed that (1'S,2S)-4-amino-N-(1'-carbamoyl-2'-phenylethyl)-2-(4''-methyl
      1''-naphthalenesulfonylamino)butanamide (J-2156), a superagonist at the h sst4
      with higher efficacy than somatostatin-14 itself (Engstrom et al., 2005), was
      considerably less prone to cause desensitization of the EAR response than
      somatostatin-14, somatostatin-28, and cortistatin-17. In contrast, compound A
      (methyl (2S)-5-{[amino(imino)methyl]amino}-2-{[4-[5-7-difluoro-2-phenyl-1H-indol
      3-yl)butanoyl]amino}-pentanoate), which we also found to be an h sst(4)
      superagonist, albeit to a lesser degree than J-2156, demonstrated a high
      propensity to cause desensitization. Our results indicate that there is no
      relationship between the efficacy of the agonists to cause G-protein activation
      and their ability to induce desensitization of the h sst4-mediated EAR responses.
      The finding that on the h sst4, J-2156 is not only a superagonist but also shows
      a low propensity to cause desensitization, might offer therapeutic advantages. At
      a minimum, the compound will be a powerful tool to study the mechanisms connected
      to efficacy and desensitization of h sst4-mediated responses.

PMID- 16291732
TI  - An assessment of the utility of the yeast GreenScreen assay in pharmaceutical
      screening.
AB  - In this paper we describe an initial reproducibility study of 12 proprietary
      compounds followed by the assessment of 51 marketed pharmaceuticals and, lastly,
      a summary of the data so far from 2698 proprietary compounds from the Johnson &
      Johnson (J&J) compound library, in the yeast GreenScreen assay (GSA). In this
      assay, a reporter system in the yeast cells employs the DNA damage inducible
      promoter of the RAD54 gene, fused to the extremely stable green fluorescent
      protein (GFP). The assay proved to be very robust, the Excel templates provided
      by Gentronix with the assay interfaced well with in-house J&J systems with little
      adaptation, the assay was very rapid to perform and used very little compound.
      The results confirm previous work which suggests that the yeast GSA detects
      different classes of genotoxic compounds to the Ames assay and as a result can
      help screen out important genotoxic compounds at the pre-regulatory test phase
      that are missed by Ames-test-based screens alone. A combination of SAR evaluation
      of genotoxicity plus an Ames-test-based screen and the GSA provides a powerful
      pre-regulatory test battery to aid in the selection of successful drug
      candidates.

PMID- 16291733
TI  - Disparate clinical presentation of neonatal hemochromatosis in twins.
AB  - Neonatal hemochromatosis (NH) is a rare disease of gestation that results in
      fetal liver injury and extrahepatic siderosis. The etiology of NH is not fully
      understood. However, the rate of recurrence of NH in the pregnancy after an
      affected one is approximately 80%. A spectrum of liver disease has been
      recognized, spanning from liver failure in the fetus or neonate to infants that
      survive with medical therapy. Here we report on 2 sets of fraternal twins, each
      set with a gross disparity in the severity of presentation: 1 infant with liver
      failure and the other nearly unaffected. These findings suggest a need to look
      carefully for subclinical disease in the siblings of patients with NH by using
      sensitive tests such as those for ferritin and alpha-fetoprotein. They also
      suggest that affected infants may be missed when using routine clinical testing,
      which would lead to the apparent rate of recurrence, understating the actual
      recurrence rate.

PMID- 16291734
TI  - Changes in the epidemiology of thalassemia in North America: a new minority
      disease.
AB  - OBJECTIVE: Changing patterns of immigration to North America, along with improved
      treatment, have altered the clinical spectrum of thalassemia, one of the world's
      most common genetic diseases. The new demography of the disease, with its widely
      variable phenotypes, has implications for its diagnosis, counseling, and
      management. Characterization of the new spectrum of this ancient disease, now
      predominated by minority groups, is essential for optimizing survival. METHODS:
      The National Institutes of Health-sponsored North American Thalassemia Clinical
      Research Network (TCRN) conducted a cross-sectional study of 721 patients with
      thalassemia syndromes. A detailed chart review was undertaken to define the
      relationships between ethnic origins, genotype, and phenotype. These results were
      compared with 3 previous surveys of similar regions. To determine if the TCRN
      patient epidemiology is representative of North American patients, 87 additional
      programs were reviewed, and hemoglobinopathy programs from the 2 largest
      thalassemia regions, Ontario and California, were analyzed. RESULTS: A total of
      721 patients completed analysis in the TCRN study, including 389 (54%) patients
      with beta-thalassemia major, 105 (15%) patients with beta-thalassemia intermedia,
      95 (13%) patients with hemoglobin E-beta-thalassemia, and 132 (18%) patients with
      alpha-thalassemia. beta-Thalassemia predominated in Eastern North America.
      Hemoglobin E-beta-thalassemia and alpha-thalassemia were common on the Western
      continent. Genotype broadly correlated with the clinical phenotype. However,
      there was marked heterogeneity in clinical phenotype among patients with similar
      globin mutations. In beta-thalassemia disorders, coinheritance of the alpha
      thalassemia trait, triplication of alpha-thalassemia genes, and heterozygosity
      for the dominant beta-thalassemia allele affected the clinical phenotype. In
      alpha-thalassemia disorders, structural mutations such as hemoglobin H-Constant
      Spring resulted in a severe hemoglobin H phenotype. Sixty percent of patients
      received regular transfusions, and 86% received regular iron-chelation therapy.
      Increased survival and decreasing birth rates of Mediterranean patients resulted
      in an aging Greek/Italian population being replaced by a young Asian/Middle
      Eastern population. Now, Asian patients account for >50% of the thalassemia
      population. Evidence of increasing survival is reflected in an advancing mean age
      of white patients with thalassemia major (25 years, up from 11 years in 1974).
      The results of the non-TCRN thalassemia survey confirm these observations and
      describe a young multiethnic thalassemia population distributed throughout North
      America. Newborn-screening results suggest that thalassemia births in North
      America are increasing and reflect the change in genotype and phenotype observed
      in the TCRN populations. CONCLUSIONS: The epidemiology of thalassemia in North
      America reflects a heterogeneous group of diseases with new ethnicities,
      genotypes, and phenotypes. In these communities, physicians will need to provide
      education, prenatal diagnosis, counseling, and management of this newly diverse
      group of patients.

PMID- 16291735
TI  - Tenofovir disoproxil fumarate and an optimized background regimen of
      antiretroviral agents as salvage therapy for pediatric HIV infection.
AB  - OBJECTIVES: Highly active antiretroviral therapy has altered the course of HIV
      infection among children, but new antiretroviral agents are needed for treatment
      experienced children with drug-resistant virus. Tenofovir disoproxil fumarate
      (DF) is a promising agent for use in pediatric salvage therapy, because of its
      tolerability, efficacy, and resistance profile. We designed this study to provide
      preliminary pediatric safety and dosing information on tenofovir DF, while also
      providing potentially efficacious salvage therapy for heavily treatment
      experienced, HIV-infected children. METHODS: Tenofovir DF, alone and in
      combination with optimized background antiretroviral regimens, was studied among
      18 HIV-infected children (age range: 8.3-16.2 years) who had progressive disease
      with > or = 2 prior antiretroviral regimens, in a single-center, open-label
      trial. Tenofovir DF monotherapy for 6 days was followed by the addition of
      individualized antiretroviral regimens. Subjects were monitored with HIV RNA
      reverse transcription-polymerase chain reaction, flow cytometry, and routine
      laboratory studies; monitoring for bone toxicity included measurement of lumbar
      spine bone mineral density (BMD) with dual-energy x-ray absorptiometry. Subjects
      were monitored through 48 weeks. RESULTS: Two subjects developed grade 3 elevated
      hepatic transaminase levels during monotherapy and were removed from the study.
      The remaining 16 subjects had a median of 4 antiretroviral agents (range: 3-5
      agents) added to tenofovir DF. HIV plasma RNA levels decreased from a median
      pretreatment level of 5.4 log10 copies per mL (range: 4.1-5.9 log10 copies per
      mL) to 4.21 log10 copies per mL at week 48 (n = 15), with 6 subjects having < 400
      copies per mL, including 4 with < 50 copies per mL. The overall median increases
      in CD4+ T cell counts were 58 cells per mm3 (range: -64 to 589 cells per mm3) at
      week 24 and 0 cells per mm3 (range: -274 to 768 cells per mm3) at week 48. The
      CD4+ cell responses among the virologic responders were high and sustained. The
      major toxicity attributed to tenofovir DF was a >6% decrease in BMD for 5 of 15
      subjects evaluated at week 48, necessitating the discontinuation of tenofovir DF
      therapy for 2; all 5 subjects experienced >2 log10 copies per mL decreases in HIV
      plasma RNA levels. CONCLUSIONS: Tenofovir DF-containing, individualized, highly
      active antiretroviral therapy regimens were well tolerated and effective among
      heavily treatment-experienced, HIV-infected children. Loss of BMD may limit
      tenofovir DF use among prepubertal patients.

PMID- 16291736
TI  - Distinctive morphological and gene/protein expression signatures during
      myogenesis in novel cell lines from extraocular and hindlimb muscle.
AB  - Skeletal muscles are not created equal. The underutilized concept of muscle
      allotypes defines distinct muscle groups that differ in their intrinsic capacity
      to express novel traits when exposed to a facilitating extrinsic environment.
      Allotype-specific traits may have significance as determinants of the
      preferential involvement or sparing of muscle groups that is observed in a
      variety of neuromuscular diseases. Little is known, however, of the developmental
      mechanisms underlying the distinctive skeletal muscle allotypes. The lack of
      appropriate in vitro models, to dissociate the cell-autonomous and non-cell
      autonomous mechanisms behind allotype diversity, has been a barrier to such
      studies. Here, we derived novel cell lines from the extraocular and hindlimb
      muscle allotypes and assessed their similarities and differences during early
      myogenesis using morphological and gene/protein expression profiling tools. Our
      data establish that there are fundamental differences in the transcriptional and
      cellular signaling pathways used by the two myoblast lineages. Taken together,
      these data show that myoblast lineage plays a significant role in the divergence
      of the distinctive muscle groups or allotypes.

PMID- 16291737
TI  - Expression profiling of purified male germ cells: stage-specific expression
      patterns related to meiosis and postmeiotic development.
AB  - Gene expression profiling was performed using the National Institute on Aging
      15,000-cDNA microarray to reveal the differential expression pattern of 160 genes
      between meiotic pachytene spermatocytes and postmeiotic round spermatids of the
      mouse. Our results indicate that more genes are expressed in spermatids than in
      spermatocytes. Genes participating in cell cycle regulation and chromatin
      structure and dynamics are preferentially expressed in spermatocytes, while genes
      for protein turnover, signal transduction, energy metabolism, and intracellular
      transport are prevalent in spermatids. This suggests that a switch of functional
      requirement occurs when meiotic germ cells differentiate into haploid spermatids.
      Concordant expression patterns were obtained when quantitative real-time
      polymerase chain reaction was performed to verify the microarray data.
      Interestingly, the majority of the differentially expressed genes were
      underrepresented in mitotic type A spermatogonia, and they were preferentially
      expressed in the testis. Our results suggest that an even higher proportion of
      the mouse genome is devoted to male gamete development from meiosis than was
      previously estimated. We also provide evidence that underscores the advantage of
      using purified germ cells over whole testes in profiling spermatogenic gene
      expression to identify transcripts that demonstrate stage-specific expression
      patterns.

PMID- 16291738
TI  - Structural and spectroscopic studies shed light on the mechanism of oxalate
      oxidase.
AB  - Oxalate oxidase (EC 1.2.3.4) catalyzes the conversion of oxalate and dioxygen to
      hydrogen peroxide and carbon dioxide. In this study, glycolate was used as a
      structural analogue of oxalate to investigate substrate binding in the
      crystalline enzyme. The observed monodentate binding of glycolate to the active
      site manganese ion of oxalate oxidase is consistent with a mechanism involving C
      C bond cleavage driven by superoxide anion attack on a monodentate coordinated
      substrate. In this mechanism, the metal serves two functions: to organize the
      substrates (oxalate and dioxygen) and to transiently reduce dioxygen. The
      observed structure further implies important roles for specific active site
      residues (two asparagines and one glutamine) in correctly orientating the
      substrates and reaction intermediates for catalysis. Combined spectroscopic,
      biochemical, and structural analyses of mutants confirms the importance of the
      asparagine residues in organizing a functional active site complex.

PMID- 16291739
TI  - Leukemia inhibitory factor induces DNA synthesis in Swiss mouse 3T3 cells
      independently of cyclin D1 expression through a mechanism involving MEK/ERK1/2
      activation.
AB  - Leukemia inhibitory factor (LIF) and oncostatin M (OSM) induce DNA synthesis in
      Swiss 3T3 cells through common signaling mechanism(s), whereas other related
      cytokines such as interleukin-6 and ciliary neurotrophic factor do not cause this
      response. Induction of DNA replication by LIF or prostaglandin F2alpha
      (PGF2alpha) occurs, in part, through different signaling events. LIF and OSM
      specifically trigger STAT1 cytoplasmic to nuclear translocation, whereas
      PGF2alpha fails to do so. However, LIF and PGF2alpha can trigger increases in
      ERK1/2 activity, which are required for their mitogenic responses because U0126,
      a MEK1/2 inhibitor, prevents both ERK1/2 activation and induction of DNA
      synthesis by LIF or PGF2alpha treatment. PGF2alpha induces cyclin D expression
      and full phosphorylation of retinoblastoma protein. In contrast, LIF fails to
      promote increases in cyclin D mRNA/protein levels; consequently, LIF induces DNA
      synthesis without promoting full phosphorylation of retinoblastoma protein (Rb).
      However, both LIF and PGF2alpha increase cyclin E expression. Furthermore, LIF
      mitogenic action does not involve protein kinase C (PKC) activation, because a
      PKC inhibitor does not block this effect. In contrast, PKC activity is required
      for PGF2alpha mitogenic action. More importantly, the synergistic effect between
      LIF and PGF2alpha to promote S phase entry is independent of PKC activation.
      These results show fundamental differences between LIF- and PGF2alpha-dependent
      mechanism(s) that induce cellular entry into S phase. These findings are critical
      in understanding how LIF and other related cytokine-regulated events participate
      in normal cell cycle control and may also provide clues to unravel crucial
      processes underlying cancerous cell division.

PMID- 16291740
TI  - Charge modification at multiple C-terminal lysine residues regulates p53
      oligomerization and its nucleus-cytoplasm trafficking.
AB  - The basal level of the tumor suppressor p53 is regulated by MDM2-mediated
      ubiquitination at specific lysines, which leads to p53 nuclear export and
      degradation. Upon p53 activation, however, these lysines become acetylated by
      p300/CREB-binding protein. Here we have reported an unexpected finding that p300
      mediated acetylation also regulates p53 subcellular localization and can promote
      cytoplasmic localization of p53. This activity is independent of MDM2 but
      requires a p53 nuclear export signal and acetylation of multiple lysines by p300.
      Mechanistically, we showed that conversion of a minimal four of these lysines to
      alanines but not arginines mimics p300-mediated p53 nuclear export, and these
      lysine-neutralizing mutations effectively prevent p53 tetramerization, thus
      exposing the oligomerization-regulated nuclear export signal. Our study suggested
      a threshold mechanism whereby the degree of acetylation regulates p53 nucleus
      cytoplasm trafficking by neutralizing a lysine-dependent charge patch, which in
      turn, controls oligomerization-dependent p53 nuclear export.

PMID- 16291741
TI  - Adult tissue-specific expression of a Dppa3-derived retrogene represents a
      postnatal transcript of pluripotent cell origin.
AB  - Processed pseudogenes emerge by reverse transcription of spliced mRNAs followed
      by incorporation of the resultant cDNA into the genome. Their genesis requires
      that retrotransposition occurs within the germ line, a provision that
      significantly limits random distribution of source genes. We previously
      identified embryonic stem cell-specific genes as an enriched source of
      retropseudogene origin. Nanog, Oct4, and Dppa3 (Stella/PGC7) presented as source
      genes for >30 processed pseudogenes within the human genome. In the current
      study, we extended our previous analysis and focused on the pluripotent cell
      specific Dppa gene family. Of the five Dppa genes characterized, four were
      associated with putative retropseudogenes as determined by nucleotide BLAST
      (basic local alignment sequence tool) searches of the respective mRNA transcripts
      against the human genome. A subset of the 11 Dppa3-derived hits were then
      screened against a human adult tissue cDNA panel for evidence of transcriptional
      activity. One of the putative Dppa3-derived retropseudogenes, Dppa3(d), located
      on human chromosome 16p13, tested positive for mRNA transcript in bone marrow,
      peripheral blood, pancreas, adrenal gland, and thyroid gland. Specificity against
      the source Dppa3 gene expression was sequence verified, and independent human
      tissue samples were obtained to confirm Dppa3(d) expression. These data
      substantiate the existence of human adult tissue-specific transcripts that
      originate via retrotransposition of the pluripotent cell-specific gene, Dppa3.
      Further studies may reveal an evolutionary role for this example of genetic
      diversity, but in the short term our observations serve a cautionary purpose
      regarding the use of Dppa3 transcripts in adult tissue-derived cells as a
      potential marker of pluripotency.

PMID- 16291742
TI  - Human SOD1 before harboring the catalytic metal: solution structure of copper
      depleted, disulfide-reduced form.
AB  - SOD1 has to undergo several post-translational modifications before reaching its
      mature form. The protein requires insertion of zinc and copper atoms, followed by
      the formation of a conserved S-S bond between Cys-57 and Cys-146 (human
      numbering), which makes the protein fully active. In this report an NMR
      structural investigation of the reduced SH-SH form of thermostable E,Zn-as-SOD1
      (E is empty; as is C6A, C111S) is reported, characterizing the protein just
      before the last step leading to the mature form. The structure is compared with
      that of the oxidized S-S form as well as with that of the yeast SOD1 complexed
      with its copper chaperone, CCS. Local conformational rearrangements upon
      disulfide bridge reduction are localized in the region near Cys-57 that is
      completely exposed to the solvent in the present structure, at variance with the
      oxidized forms. There is a local disorder around Cys-57 that may serve for
      protein-protein recognition and may possibly be involved in intermolecular S-S
      bonds in familial amyotrophic lateral sclerosis-related SOD1 mutants. The
      structure allows us to further discuss the copper loading mechanism in SOD1.

PMID- 16291743
TI  - Dissection of a circumscribed recombination hot spot in HIV-1 after a single
      infectious cycle.
AB  - Recombination is a major source of genetic heterogeneity in the human
      immunodeficiency virus type 1 (HIV-1) population. The main mechanism responsible
      for the generation of recombinant viruses is a process of copy choice between the
      two copies of genomic RNA during reverse transcription. We previously identified,
      after a single cycle of infection of cells in culture, a recombination hot spot
      within the gp120 gene, corresponding to the top portion of a RNA hairpin. Here,
      we determine that the hot region is circumscribed to 18 nucleotides located in
      the descending strand of the stem, following the sense of reverse transcription.
      Three factors appeared to be important, albeit at different extents, for the high
      rate of recombination observed in this region. The position of the hot sequence
      in the context of the RNA structure appears crucial, because changing its
      location within this structure triggered differences in recombination up to 20
      fold. Another pivotal factor is the presence of a perfectly identical sequence
      between donor and acceptor RNA in the region of transfer, because single or
      double nucleotide differences in the hot spot were sufficient to almost
      completely abolish recombination in the region. Last, the primary structure of
      the hot region also influenced recombination, although with effects only in the 2
      3-fold range. Altogether, these results provide the first molecular dissection of
      a hot spot in infected cells and indicate that several factors contribute to the
      generation of a site of preferential copy choice.

PMID- 16291744
TI  - Phosphorylated alpha-actinin and protein-tyrosine phosphatase 1B coregulate the
      disassembly of the focal adhesion kinase x Src complex and promote cell
      migration.
AB  - The focal adhesion kinase (FAK) is a key regulator of cell migration.
      Phosphorylation at Tyr-397 activates FAK and creates a binding site for Src
      family kinases. FAK phosphorylates the cytoskeletal protein alpha-actinin at Tyr
      12. Here we report that protein-tyrosine phosphatase 1B (PTP 1B) is an alpha
      actinin phosphatase. PTP 1B-dependent dephosphorylation of alpha-actinin was seen
      in COS-7 cells and PTP 1B-null fibroblasts reconstituted with PTP 1B.
      Furthermore, we show that coexpression of wild-type alpha-actinin and PTP 1B
      causes dephosphorylation at Tyr-397 in FAK. No dephosphorylation was observed in
      cells coexpressing the alpha-actinin phosphorylation mutant Y12F and PTP 1B.
      Furthermore, the phosphorylation at four other sites in FAK was not altered by
      PTP 1B. In addition, we found that phosphorylated alpha-actinin bound to Src and
      reduced the binding of FAK to Src. The dephosphorylation at Tyr-397 in FAK
      triggered by wild-type alpha-actinin and PTP 1B caused a significant increase in
      cell migration. We propose that phosphorylated alpha-actinin disrupts the FAK x
      Src complex exposing Tyr-397 in FAK to PTP 1B. These findings uncover a novel
      feedback loop involving phosphorylated alpha-actinin and PTP 1B that regulates
      FAK x Src interaction and cell migration.

PMID- 16291745
TI  - A soluble pyrophosphatase, a key enzyme for polyphosphate metabolism in
      Leishmania.
AB  - We report the functional characterization in Leishmania amazonensis of a soluble
      pyrophosphatase (LaVSP1) that localizes in acidocalcisomes, a vesicular acidic
      compartment. LaVSP1 is preferentially expressed in metacyclic forms. Experiments
      with dominant negative mutants show the requirement of LaVSP1 functional
      expression for metacyclogenesis and virulence in mice. Depending on the pH and
      the cofactors Mg2+ or Zn2+, both present in acidocalcisomes, LaVSP1 hydrolyzes
      either inorganic pyrophosphate (Km = 92 microM, kcat = 125 s(-1)),
      tripolyphosphate (Km = 1153 microM, kcat = 131 s(-1)), or polyphosphate of 28
      residues (Km = 123 microM, kcat = 8 s(-1)). Predicted structural analysis
      suggests that the structural orientation of the residue Lys78 in LaVSP1 accounts
      for the observed increase in Km compared with the yeast pyrophosphatase and for
      the ability of trypanosomatid VSP1 enzymes to hydrolyze polyphosphate. These
      results make the VSP1 enzyme an attractive drug target against trypanosomatid
      parasites.

PMID- 16291746
TI  - On the mechanism of mitochondrial uncoupling protein 1 function.
AB  - Native uncoupling protein 1 (UCP 1) was purified from rat mitochondria by
      hydroxyapatite chromatography and identified by peptide mass mapping and tandem
      mass spectrometry. Native and expressed UCP 1 were reconstituted into liposomes,
      and proton flux through UCP 1 was shown to be fatty acid-dependent and GDP
      sensitive. To investigate the mechanism of action of UCP 1, we determined whether
      hydrophilic modification of the omega-carbon of palmitate effected its transport
      function. We show that proton flux was greater through native UCP 1-containing
      proteoliposomes when facilitated by less hydrophilically modified palmitate
      (palmitate > omega-methoxypalmitate > omega-hydroxypalmitate with little or no
      proton flux due to glucose-O-omega-palmitate or undecanesulfonate). We show that
      non-proton-dependent charge transfer was greater when facilitated by less
      hydrophilically modified palmitate (palmitate/undecanesulfonate > omega
      methoxypalmitate > omega-hydroxypalmitate, with no non-proton-dependent charge
      transfer flux due to glucose-O-omega-palmitate). We show that the GDP-inhibitable
      oxygen consumption rate in brown adipose tissue mitochondria was reversed by
      palmitate (as expected) but not by glucose-O-omega-palmitate. Our data are
      consistent with the model that UCP 1 flips long-chain fatty acid anions and
      contradict the "cofactor" model of UCP 1 function.

PMID- 16291747
TI  - BCR-ABL regulates phosphatidylinositol 3-kinase-p110gamma transcription and
      activation and is required for proliferation and drug resistance.
AB  - The BCR-ABL oncogene is the hallmark of chronic myeloid leukemia, a clonal
      hematopoietic stem cell disorder. BCR-ABL displays constitutive tyrosine kinase
      activity, required for its transformation ability. Although the molecular
      mechanisms behind this malignancy are not fully understood, a role for
      phosphatidylinositol (PI) 3-kinase has been repeatedly described. Here we report
      the specific up-regulation of the class I(B) catalytic subunit of PI 3-kinase
      (p110gamma) in response to BCR-ABL expression. We demonstrate that this
      upregulation is due to increased transcription and is dependent on both PI 3
      kinase and MEK activity. We performed in vitro kinase activity assays and show
      that BCR-ABL also leads to increased p110gamma activity and that this activation
      requires both G protein-coupled receptor and Ras signaling. In addition, by
      transfection of cells with dominant negative p110gamma, we determined that this
      specific PI 3-kinase isoform is involved in both proliferation and the apoptosis
      resistance associated with chronic myeloid leukemia. The data presented here
      define for the first time the ability of BCR-ABL to alter the expression levels
      of PI 3-kinase isoforms and also demonstrate a previously unreported link between
      BCR-ABL and p110gamma.

PMID- 16291748
TI  - Identification of the mitochondrial NAD+ transporter in Saccharomyces cerevisiae.
AB  - The mitochondrial carriers are a family of transport proteins that shuttle
      metabolites, nucleotides, and cofactors across the inner mitochondrial membrane.
      In Saccharomyces cerevisiae, NAD+ is synthesized outside the mitochondria and
      must be imported across the permeability barrier of the inner mitochondrial
      membrane. However, no protein responsible for this transport activity has ever
      been isolated or identified. In this report, the identification and functional
      characterization of the mitochondrial NAD+ carrier protein (Ndt1p) is described.
      The NDT1 gene was overexpressed in bacteria. The purified protein was
      reconstituted into liposomes, and its transport properties and kinetic parameters
      were characterized. It transported NAD+ and, to a lesser extent, (d)AMP and
      (d)GMP but virtually not alpha-NAD+, NADH, NADP+, or NADPH. Transport was
      saturable with an apparent Km of 0.38 mM for NAD+. The Ndt1p-GFP was found to be
      targeted to mitochondria. Consistently with Ndt1p localization and its function
      as a NAD+ transporter, cells lacking NDT1 had reduced levels of NAD+ and NADH in
      their mitochondria and reduced activity of mitochondrial NAD+-requiring enzymes.
      Similar results were also found in the mitochondria of cells lacking NDT2 that
      encodes a protein (Ndt2p) displaying 70% homology with Ndt1p. The delta ndt1
      delta ndt2 double mutant exhibited lower mitochondrial NAD+ and NADH levels than
      the single deletants and a more pronounced delay in growth on nonfermentable
      carbon sources. The main role of Ndt1p and Ndt2p is to import NAD+ into
      mitochondria by unidirectional transport or by exchange with intramitochondrially
      generated (d)AMP and (d)GMP.

PMID- 16291749
TI  - A C-terminal domain in KCC2 confers constitutive K+-Cl- cotransport.
AB  - The neuron-specific K(+)-Cl(-) cotransporter KCC2 plays a crucial role in
      determining intracellular chloride activity and thus the neuronal response to
      gamma-aminobutyric acid and glycine. Of the four KCCs, KCC2 is unique in
      mediating constitutive K(+)-Cl(-) cotransport under isotonic conditions; the
      other three KCCs are exclusively swelling-activated, with no isotonic activity.
      We have utilized a series of chimeric cDNAs to localize the determinant of
      isotonic transport in KCC2. Two generations of chimeric KCC4-KCC2 cDNAs initially
      localized this characteristic to within a KCC2-specific expansion of the
      cytoplasmic C terminus, between residues 929 and 1043. This region of KCC2 is
      rich in prolines, serines, and charged residues and encompasses two predicted
      PEST sequences. Substitution of this region in KCC2 with the equivalent sequence
      of KCC4 resulted in a chimeric KCC that was devoid of isotonic activity, with
      intact swelling-activated transport. A third generation of chimeras demonstrated
      that a domain just distal to the PEST sequences confers isotonic transport on
      KCC4. Mutagenesis of this region revealed that residues 1021-1035 of KCC2 are
      sufficient for isotonic transport. Swelling-activated K(+)-Cl(-) cotransport is
      abrogated by calyculin A, whereas isotonic transport mediated by KCC chimeras and
      KCC2 is completely resistant to this serine-threonine phosphatase inhibitor. In
      summary, a 15-residue C-terminal domain in KCC2 is both necessary and sufficient
      for constitutive K(+)-Cl(-) cotransport under isotonic conditions. Furthermore,
      unlike swelling-activated transport, constitutive K(+)-Cl(-) cotransport mediated
      by KCC2 is completely independent of serine-threonine phosphatase activity,
      suggesting that these two modes of transport are activated by distinct
      mechanisms.

PMID- 16291750
TI  - Genetic demonstration that the plasma membrane maxianion channel and voltage
      dependent anion channels are unrelated proteins.
AB  - The maxianion channel is widely expressed in many cell types, where it fulfills a
      general physiological function as an ATP-conductive gate for cell-to-cell
      purinergic signaling. Establishing the molecular identity of this channel is
      crucial to understanding the mechanisms of regulated ATP release. A mitochondrial
      porin (voltage-dependent anion channel (VDAC)) located in the plasma membrane has
      long been considered as the molecule underlying the maxianion channel activity,
      based upon similarities in the biophysical properties of these two channels and
      the purported presence of VDAC protein in the plasma membrane. We have deleted
      each of the three genes encoding the VDAC isoforms individually and collectively
      and demonstrate that maxianion channel (approximately 400 picosiemens) activity
      in VDAC-deficient mouse fibroblasts is unaltered. The channel activity is similar
      in VDAC1/VDAC3-double-deficient cells and in double-deficient cells with the
      VDAC2 protein depleted by RNA interference. VDAC deletion slightly down
      regulated, but never abolished, the swelling-induced ATP release. The lack of
      correlation between VDAC protein expression and maxianion channel activity
      strongly argues against the long held hypothesis of plasmalemmal VDAC being the
      maxianion channel.

PMID- 16291751
TI  - Distinct pathways regulate proapoptotic Nix and BNip3 in cardiac stress.
AB  - Up-regulation of myocardial Nix and BNip3 is associated with apoptosis in cardiac
      hypertrophy and ischemia, respectively. To identify mechanisms of gene regulation
      for these critical cardiac apoptosis effectors, the determinants of Nix and BNip3
      promoter activation were elucidated by luciferase reporter gene expression in
      neonatal rat cardiac myocytes. BNip3 transcription was increased by hypoxia but
      not by phenylephrine (10 microM), angiotensin II (100 nM), or isoproterenol (10
      microM). In contrast, Nix transcription was increased by phenylephrine but not by
      isoproterenol, angiotensin II, or hypoxia. Since phenylephrine stimulates
      cardiomyocyte hypertrophy via protein kinase C (PKC), the effects of phorbol
      myristate acetate (PMA, 10 nM for 24 h) and adenoviral PKC expression were
      assessed. PMA and PKC alpha, but not PKC epsilon or dominant negative PKC alpha,
      increased Nix transcription. Multiple Nix promoter GC boxes bound transcription
      factor Sp-1, and basal and PMA- or PKC alpha-stimulated Nix promoter activity was
      suppressed by mithramycin inhibition of Sp1-DNA interactions. In vivo
      determinants of Nix expression were evaluated in Nix promoter-luciferase (NixP)
      transgenic mice that underwent ischemia-reperfusion (1 h/24 h), transverse aortic
      coarctation (TAC), or cross-breeding with the G(q) overexpression model of
      hypertrophy. Luciferase activity increased in G alpha(q)-NixP hearts 3.2 +/- 0.4
      fold and in TAC hearts 2.8 +/- 0.4-fold but did not increase with infarction
      reperfusion. NixP activity was proportional to the extent of TAC hypertrophy and
      was inhibited by mithramycin. These studies revealed distinct mechanisms of
      transcriptional regulation for cardiac Nix and BNip3. BNip3 is hypoxia-inducible,
      whereas Nix expression was induced by G alpha(q)-mediated hypertrophic stimuli.
      PKC alpha, a G(q) effector, transduced Nix transcriptional induction via Sp1.

PMID- 16291752
TI  - Molecular analysis of survivin isoforms: evidence that alternatively spliced
      variants do not play a role in mitosis.
AB  - Survivin is a protein with proposed roles in cell division and apoptosis.
      Transcripts encoding splice variants of human survivin have been described and
      their expression correlated with cancer progression. As survivin forms homodimers
      in vitro, it has been suggested that these isoforms could interfere with wild
      type function by forming heterodimers. Here we show that survivin-2beta and
      survivin-deltaEx3 can interact with wild type survivin but have reduced affinity
      for the partner protein of survivin, borealin, and thus do not localize with the
      chromosomal passenger complex in vivo. Furthermore, we demonstrate that
      overexpression of survivin-2beta-green fluorescent protein (GFP) or survivin
      deltaEx3-GFP does not impede cell cycle progression. We also report that wild
      type survivin, but not survivin-2beta-GFP or survivin-deltaEx3-GFP, can rescue
      cell proliferation inhibited by small interfering RNA-mediated survivin
      depletion. These data suggest that, despite their ability to interact with wild
      type survivin, neither of these isoforms acts as its competitor during mitosis
      nor has an essential function.

PMID- 16291753
TI  - A splice variant of stress response gene ATF3 counteracts NF-kappaB-dependent
      anti-apoptosis through inhibiting recruitment of CREB-binding protein/p300
      coactivator.
AB  - Activating transcription factor (ATF) 3 plays a role in determining cell fate and
      generates a variety of alternatively spliced isoforms in stress response. We have
      reported previously that splice variant ATF3deltaZip2, which lacks the leucine
      zipper region, is induced in response to various stress stimuli. However, its
      biological function has not been elucidated. By using cells treated with tumor
      necrosis factor-alpha and actinomycin D or cells overexpressing ATF3deltaZip2, we
      showed that ATF3deltaZip2 sensitizes cells to apoptotic cell death in response to
      tumor necrosis factor-alpha, at least in part through suppressing nuclear factor
      (NF)-kappaB-dependent transcription of anti-apoptotic genes such as cIAP2 and
      XIAP. ATF3deltaZip2 interacts with a p65 (RelA)-cofactor complex containing
      CBP/p300 and HDAC1 at NF-kappaB sites of the proximal promoter region of the
      cIAP2 gene in vivo and down-regulates the recruitment of CBP/p300. Our study
      revealed that ATF3deltaZip2 counteracts anti-apoptotic activity of NF-kappaB, at
      least in part, by displacing positive cofactor CBP/p300 and provides insight into
      the mechanism by which ATF3 regulates cell fate through alternative splicing in
      stress response.

PMID- 16291754
TI  - Identification by mutational analysis of amino acid residues essential in the
      chaperone function of calreticulin.
AB  - Calreticulin is a Ca2+ -binding chaperone that resides in the lumen of the
      endoplasmic reticulum and is involved in the regulation of intracellular Ca2+
      homeostasis and in the folding of newly synthesized glycoproteins. In this study,
      we have used site-specific mutagenesis to map amino acid residues that are
      critical in calreticulin function. We have focused on two cysteine residues
      (Cys(88) and Cys(120)), which form a disulfide bridge in the N-terminal domain of
      calreticulin, on a tryptophan residue located in the carbohydrate binding site
      (Trp(302)), and on certain residues located at the tip of the "hairpin-like" P
      domain of the protein (Glu(238), Glu(239), Asp(241), Glu(243), and Trp(244)).
      Calreticulin mutants were expressed in crt(-/-) fibroblasts, and bradykinin
      dependent Ca2+ release was measured as a marker of calreticulin function.
      Bradykinin-dependent Ca2+ release from the endoplasmic reticulum was rescued by
      wild-type calreticulin and by the Glu(238), Glu(239), Asp(241), and Glu(243)
      mutants. The Cys(88) and Cys(120) mutants rescued the calreticulin-deficient
      phenotype only partially ( approximately 40%), and the Trp(244) and Trp(302)
      mutants did not rescue it at all. We identified four amino acid residues
      (Glu(239), Asp(241), Glu(243), and Trp(244)) at the hairpin tip of the P-domain
      that are critical in the formation of a complex between ERp57 and calreticulin.
      Although the Glu(239), Asp(241), and Glu(243) mutants did not bind ERp57
      efficiently, they fully restored bradykinin-dependent Ca2+ release in crt(-/-)
      cells. This indicates that binding of ERp57 to calreticulin may not be critical
      for the chaperone function of calreticulin with respect to the bradykinin
      receptor.

PMID- 16291755
TI  - The tyrosine kinase Syk regulates TPL2 activation signals.
AB  - Tpl2/Cot is a serine/threonine kinase that plays a key physiological role in the
      regulation of immune responses to pro-inflammatory stimuli, including tumor
      necrosis factor-alpha (TNF-alpha). TNF-alpha stimulates the JNK, ERK, and p38
      mitogen-activated protein kinases and the NF-kappaB pathway by recruiting RIP1
      and TRAF2 to the TNF receptor 1. Here we showed that Tpl2 activation by TNF-alpha
      signals depends on the integrity of the Tpl2-interacting proteins RIP1 and TRAF2,
      which are required for the engagement of the ERK mitogen-activated protein kinase
      pathway. However, neither RIP1 nor TRAF2 overexpression was sufficient to
      activate Tpl2 and ERK. We also showed that Tpl2 activation by TNF-alpha depends
      on a tyrosine kinase activity that is detected in TNF-alpha-stimulated cells.
      Based on both genetic and biochemical evidence, we concluded that in a variety of
      cell types, Syk is the tyrosine kinase that plays an important role in the
      activation of Tpl2 upstream of ERK. These data therefore dissect the TNF receptor
      1 proximal events that regulate Tpl2 and ERK and highlight a role for RIP1,
      TRAF2, and Syk in this pathway.

PMID- 16291756
TI  - Function of positive charges following signal-anchor sequences during
      translocation of the N-terminal domain.
AB  - In topogenesis of membrane proteins on the endoplasmic reticulum, the orientation
      of the hydrophobic transmembrane (TM) segment is influenced by the charge of the
      flanking amino acid residues. We assessed the function of the positive charges
      downstream of the hydrophobic segment using synaptotagmin II. The positive
      charges were systematically replaced with non-charged residues. Although the
      original TM segment translocated the N terminus, the topology was inverted,
      depending on the mutations. Orientation was affected in mutants in which 6 Lys
      were shifted downstream, even when the 6 Lys were 25 residues from the
      hydrophobic segment. The Lys was functionally replaced by Arg, but not by Asp or
      Glu. The timing of action during polypeptide elongation indicated that the Lys
      functions at the ribosome exit sites. We suggest that the commitment of the TM
      segment to a particular orientation is influenced by far downstream parts of the
      polypeptide chain and that the positive charges are decoded after exiting the
      ribosome.

PMID- 16291757
TI  - Stress-induced response, localization, and regulation of the Pmk1 cell integrity
      pathway in Schizosaccharomyces pombe.
AB  - Mitogen-activated protein kinase (MAPK) signaling pathways are critical for the
      sensing and response of eukaryotic cells to extracellular changes. In
      Schizosaccharomyces pombe, MAPK Pmk1/Spm1 has been involved in cell wall
      construction, morphogenesis, cytokinesis, and ion homeostasis, as part of the so
      called cell integrity pathway together with MAPK kinase kinase Mkh1 and MAPK
      kinase Pek1. We show that Pmk1 is activated in multiple stress situations,
      including hyper- or hypotonic stress, glucose deprivation, presence of cell wall
      damaging compounds, and oxidative stress induced by hydrogen peroxide or pro
      oxidants. The stress-induced activation of Pmk1 was completely dependent on Mkh1
      and Pek1 function, supporting a nonbranched pathway in the regulation of MAPK
      activation. Fluorescence microscopy revealed that Mkh1, Pek1, and Pmp1 (a protein
      phosphatase that inactivates Pmk1) are cytoplasmic proteins. Mkh1 and Pek1 were
      also found at the septum, whereas Pmk1 localized in both cytoplasm and nucleus as
      well as in the mitotic spindle and septum during cytokinesis. Interestingly, Pmk1
      subcellular localization was unaffected by stress or the absence of Mkh1 and
      Pek1, suggesting that its activation by the Mkh1-Pek1 cascade takes place at the
      cytoplasm and/or septum and that the active and inactive forms of this kinase
      cross the nuclear membrane. Cdc42 GTPase and its effectors, p21-activated kinases
      Pak2 and Pak1, are not upstream elements controlling the basal level or the
      stress-induced activation of Pmk1. However, Sty1 MAPK was essential for proper
      Pmk1 deactivation after hypertonic stress in a process regulated by Atf1
      transcription factor. These results provide the first evidence for the existence
      of cross-talk between two MAPK cascades during the stress response in fission
      yeast.

PMID- 16291758
TI  - HIC-5 is a novel repressor of lymphoid enhancer factor/T-cell factor-driven
      transcription.
AB  - Activation of Wnt/beta-catenin target genes is regulated by a heterodimer of beta
      catenin and the high mobility group box transcription factors of the lymphoid
      enhancer factor (LEF)/T-cell factor (TCF) family. In vertebrates, four LEF/TCF
      family members have been identified. They all contain a conserved beta-catenin
      binding motif at the N terminus and a highly conserved high mobility group box
      for DNA binding. The core sequence between these motifs is less conserved and
      contributes to the specific properties of the individual family members. To
      identify interacting proteins that allocate specific functions to the individual
      LEF/TCF transcription factors, we performed a yeast two-hybrid screen using the
      less conserved core sequence as bait. We isolated the murine LIM protein HIC-5
      (hydrogen peroxide-induced clone 5; also termed ARA-55 (androgen receptor
      activator of 55 kDa)) and cloned the highly conserved Xenopus homolog. In
      addition, we report that the LIM domain-containing C-terminal half of HIC-5 binds
      to a conserved alternatively spliced exon in LEF/TCF transcription factors. Our
      functional analyses revealed that HIC-5 acts as negative regulator of a subset of
      LEF/TCF family members, which have been characterized as activators in reporter
      gene analyses and in the Xenopus axis induction assay. In addition, we observed a
      repressive interference of LEF/TCF family members with HIC-5-mediated activation
      of glucocorticoid-driven transcription, which again could be allocated to
      specific LEF/TCF subtypes. With the characterization of HIC-5 as a binding
      partner of the alternatively spliced exon in LEF/TCF transcription factors, we
      identified a novel molecular mechanism in the dialog of steroid and canonical Wnt
      signaling that is LEF/TCF subtype-dependent.

PMID- 16291759
TI  - Plasmodium vivax vaccine research: steps in the right direction.

PMID- 16291760
TI  - Safety and elicitation of humoral and cellular responses in colombian malaria
      naive volunteers by a Plasmodium vivax circumsporozoite protein-derived synthetic
      vaccine.
AB  - Substantial experimental evidence indicates that the Plasmodium circumsporozoite
      (CS) protein has great potential as a vaccine candidate. We tested the safety and
      immunogenicity of vaccines composed of P. vivax CS-derived synthetic peptides.
      Sixty-nine healthy, malaria-naive volunteers were randomized to receive three
      injections of placebo or synthetic proteins N, R, or C (10, 30, or 100
      microg/dose) in a double-blinded fashion. Vaccines were well tolerated and no
      serious adverse events were observed. Peptides N and R elicited humoral responses
      at all doses; peptide C elicicted these responses only at doses of 30 and 100
      microg. The N peptide at a dose of 100 microg elicited the greatest antibody
      response. Antibodies to the three peptides recognized P. vivax sporozoites in an
      immunofluorescent antibody test. Peripheral blood mononuclear cells from most
      immunized volunteers also produced interferon-gamma upon peptide in vitro
      stimulation. These vaccines appear safe, well tolerated, and immunogenic in
      malaria-naive volunteers. Further optimization and development of this vaccine is
      being attempted to conduct phase II clinical trials.

PMID- 16291761
TI  - Aotus lemurinus griseimembra monkeys: a suitable model for Plasmodium vivax
      sporozoite infection.
AB  - This study describes a successful Plasmodium vivax sporozoite infection in Aotus
      lemurinus griseimembra. Twenty-eight naive or previously infected monkeys, either
      splenectomized or spleen intact, were inoculated intravenously or subcutaneously
      with Plasmodium vivax sporozoites of the Salvador I strain or with two wild
      isolates (VCC-4 and VCC-5; Vivax-Cali-Colombia). The monkeys were successfully
      infected regardless of the parasite strain, spleen presence, or inoculation route
      and showed prepatent periods that ranged from 16 to 89 days. Only one monkey
      inoculated intravenously failed to develop parasitemia. Since immune protection
      against malaria pre-erythrocytic forms is mediated by both helper and cytolytic T
      cells that may home in the spleen and P. vivax cultures are not yet available;
      the use of spleen-intact A. lemurinus griseimembra, susceptible to both adapted
      and non-adapted strains of P. vivax sporozoites, is a valuable model for
      evaluation of pre-erythrocytic vaccine candidates.

PMID- 16291762
TI  - Antigenicity, immunogenicity, and protective efficacy of Plasmodium vivax MSP1
      PV200l: a potential malaria vaccine subunit.
AB  - The merozoite surface protein 1 (MSP-1) is expressed in all Plasmodium species
      and is considered a major malaria vaccine candidate. We found that MSP-1 from
      Plasmodium vivax (PvMSP-1) contains a region of significant sequence homology
      with the 190L subunit vaccine derived from the P. falciparum MSP-1. The fragment,
      termed Pv200L, was expressed as a recombinant protein in Escherichia coli
      (rPv200L) and used to asses its immunologic relevance as a vaccine target. A
      cross-sectional, seroepidemiologic study conducted in Buenaventura, Colombia
      showed that 52.2% (95% confidence interval [CI] = 39.8-64.3) of individuals
      previously exposed to P. vivax and 72.8% (95% CI = 61.8-82.1) of P. vivax
      infected patients had IgG antibodies to rPv200L. Immunization of BALB/c mice and
      Aotus monkeys induced IgG antibodies (titer > 10(6)) that cross-reacted with P.
      vivax parasites. Immunized monkeys displayed partial protection against a
      challenge with P. vivax blood stages. Our results suggest that Pv200L is a new
      malaria vaccine subunit and deserves further testing.

PMID- 16291763
TI  - Immunogenicity and protective efficacy of recombinant vaccine based on the
      receptor-binding domain of the Plasmodium vivax Duffy binding protein in Aotus
      monkeys.
AB  - Invasion of human erythrocytes by Plasmodium vivax requires interaction between
      Duffy binding protein (PvDBP) and the Duffy blood group antigen. The receptor
      binding domain of PvDBP lies in a conserved N-terminal, cysteine-rich region,
      region II (PvRII). PvRII is a valuable malaria subunit vaccine candidate for
      asexual blood stages. We have evaluated in Aotus monkeys the immunogenicity and
      protective efficacy of recombinant PvRII formulated in Freund's and Montanide
      ISA720 adjuvants. Specific antibody titers were determined by an enzyme-linked
      immunosorbent assay after each of three doses of 50 microg of protein
      administered by the subcutaneous route. Immunization with PvRII formulated in
      Freund's adjuvant yielded higher antibody titers than immunization with the
      Montanide ISA720 formulation and offered partial protection. Although the
      Montanide ISA720 formulation was immunogenic, it did not provide any protection.
      Given the immunogenicity and partial protection observed, further studies are
      needed to optimize the PvRII vaccine formulation with adjuvants suitable for
      human use.

PMID- 16291764
TI  - Induction of transmission-blocking immunity in Aotus monkeys by vaccination with
      a Plasmodium vivax clinical grade PVS25 recombinant protein.
AB  - Aotus monkeys were used to determine the immunogenicity of Pvs25 protein
      expressed in the zygote/ookinete surface. Animals were immunized in three times
      with 100 microg of Pvs25 formulated in Montanide ISA-720. Antibodies to Pvs25
      detected by an enzyme-linked immunosorbent assay appeared by day 30 after the
      first immunization, with a peak of antibodies levels on day 150. These antibodies
      were still detectable on day 300. Plasma samples on day 150 from experimental
      group were able to completely block the development of the parasite in Anopheles
      albimanus mosquitoes artificially fed with human isolates of Plasmodium vivax.
      Immunized Aotus monkeys were infected with blood forms of the P. vivax Salvador I
      strain and no boosting effect of blood infection on titers of antibodies to Pvs25
      was observed despite the presence of infective gametocytes. In conclusion, Pvs25
      protein formulated in Montanide ISA-720 induces efficient and long-lasting
      transmission-blocking antibodies that cannot be boosted by parasite infection.

PMID- 16291765
TI  - Plasmodium vivax: transmission-blocking immunity in a malaria-endemic area of
      Colombia.
AB  - Plasmodium vivax transmission-blocking activity was assessed in sera from acutely
      infected patients from a malaria-endemic area in Colombia. We measured reduction
      in the number of oocysts that developed in the midguts of Anopheles albimanus
      mosquitoes artificially fed with blood from these patients. Of 88 mosquito
      batches that developed infections when parasites were mixed with normal AB human
      serum, one-third (36.4%) showed full transmission-blocking activity (>or= 90%
      inhibition) when mixed with autologous sera, 29.6% showed partial activity (50
      89%), 17.0% did not block transmission (0-50%), and 17% did not enhance
      transmission. Transmission-blocking activity correlated with antibody titer by an
      immunofluorescent antibody test and decreased with the serial dilution of the
      sera. This activity disappeared at a 1:4 dilution in most sera tested. Afro
      Colombian individuals showed lower activity than other ethnic groups and febrile
      patients produced stronger inhibition than those without fever.

PMID- 16291766
TI  - Antibody response to Plasmodium vivax antigens in Fy-negative individuals from
      the Colombian Pacific coast.
AB  - The Duffy antigen (Fy) is necessary for Plasmodium vivax invasion of human
      erythrocytes. Some populations have a highly prevalent Fy-negative phenotype;
      such persons are naturally protected from P. vivax blood infection but are
      expected to completely support the P. vivax pre-erythrocytic cycle, representing
      a valuable model for studying the immune response during these parasitic stages.
      We typed 214 individuals, mostly Afro-Colombians, from a P. vivax-endemic area
      for Fy expression and determined the antibody response to P. vivax pre
      erythrocytic (sporozoites and CS) and blood-stage antigens (blood forms, P. vivax
      merozoite surface protein 1, and P. vivax Duffy binding protein [PvDBP]).
      Antibody titers to P. vivax circumsporozoite protein, P11, and N-terminal
      peptides and the number of responders were similar in Fy-negative and Fy-positive
      individuals. The number of responders to sporozoites, blood forms, and PvDBP were
      different between these groups. Thus, Fy-negative individuals from malaria
      endemic areas can be used to study the immune response to the P. vivax liver
      phase without interference of the erythrocytic cycle.

PMID- 16291767
TI  - Hemoglobin levels related to days of illness, race, and Plasmodium species in
      Colombian patients with uncomplicated malaria.
AB  - Prevalence of malaria-related anemia in disease-endemic regions of the American
      continents has been poorly studied. We describe the relationships between
      hemoglobin level and race, Plasmodium species, and days of illness in 150
      Colombian patients with uncomplicated malaria diagnosed by thick blood smear.
      Hemoglobin was measured at admission and a standardized questionnaire was used to
      determine days of illness and other variables. Associations between hemoglobin
      and the variables were estimated and adjusted according to the other covariates
      using regression analysis. Plasmodium falciparum and P. vivax were found in
      similar proportions and mild anemia was present in 50% of the patients.
      Volunteers were classified as Afro-Colombians (61%) and non-Afro-Colombians
      (39%). An inverse relationship between hemoglobin and days of illness was
      identified, and a statistical interaction was found between race and P.
      falciparum infection in determining the hemoglobin concentration. These
      observations could guide the design of research to better understand malarial
      anemia.

PMID- 16291768
TI  - Restricted genetic diversity of Plasmodium falciparum major merozoite surface
      protein 1 in isolates from Colombia.
AB  - The merozoite surface protein 1 (MSP-1) gene of Plasmodium falciparum encodes a
      major immune target under development as a malaria vaccine. In this study, we
      typed MSP-1 variable regions of parasites obtained from Buenaventura, Colombia.
      Four MSP-1 gene types were detected corresponding to prototype and recombinant K1
      and MAD20 block 4 sequences. In contrast to variability within block 4, blocks 2,
      6, and 16-17 corresponded exclusively to the MAD20 allelic type. Most (80%) blood
      samples contained multiple MSP-1 gene types. The presence of four MSP-1 variants
      within block 4 against a MAD20 background indicates that current P. falciparum
      populations in Buenaventura are derived from parasites expressing K1 and MAD20
      alleles, some of which underwent two recombination events within or flanking
      block 4. Restricted MSP-1 diversity appears to be relatively stable in
      Buenaventura and suggests that selection has resulted in the dominance of the
      MAD20 type in most of the polymorphic blocks with the exception of block 4.

PMID- 16291769
TI  - G protein signaling in the regulation of rice seed germination.
AB  - Seed germination and early seedling growth are regulated by an intricate network
      of hormonal signaling pathways. The plant hormones gibberellic acid (GA) and
      abscisic acid (ABA) are particularly important positive and negative regulators
      of these processes, respectively. In the cereal rice, mutant analysis has
      implicated heterotrimeric guanine nucleotide-binding protein (G protein)
      signaling in GA-stimulated expression of several genes, including expression of
      the gene encoding the hydrolytic enzyme alpha-amylase, which breaks down
      carbohydrate reserves and thus mobilizes nutrients that nourish the young
      seedling.

PMID- 16291770
TI  - G protein regulation of disease resistance during infection of rice with rice
      blast fungus.
AB  - When the effects of specific pathogen-produced elicitor compounds on plant cells
      are recognized by specific plant resistance (R) gene products, a local defense
      response called the hypersensitive response is triggered. Production of reactive
      oxygen species (ROS) and induction of defense genes are components of this
      response. In rice cultivars harboring null mutations in the G protein alpha
      subunit, RGA1, ROS production and defense gene induction by the rice blast fungus
      Magnaporthe grisea and its sphingolipid elicitors are reduced or delayed. These
      results implicate heterotrimeric guanine nucleotide-binding proteins (G proteins)
      as important players in plant pathogen response.

PMID- 16291771
TI  - New progestagens for contraceptive use.
AB  - The progestins have different pharmacologic properties depending upon the parent
      molecule, usually testosterone or progesterone (P), from which they are derived.
      Very small structural changes in the parent molecule may induce considerable
      differences in the activity of the derivative. In hormonal contraceptives,
      progestins represent the major agent designed for suppressing ovulation and are
      used in combination with estrogen (E) usually ethinyl-estradiol (EE). The
      development of new generations of progestins with improved selectivity profiles
      has been a great challenge. Steroidal and nonsteroidal progesterone receptor (PR)
      agonists have been synthesized as well, although the latter are still in a very
      early stage of development. Several new progestins, have been synthesized in the
      last two decades. These include dienogest (DNG), drospirenone (DRSP), Nestorone
      (NES), nomegestrol acetate (NOMAc) and trimegestone (TMG). These new progestins
      have been designed to have no androgenic or estrogenic actions and to be closer
      in activity to the physiological hormone P. DRSP differs from the classic
      progestins as it is derived from spirolactone. It is essentially an
      antimineralocorticoid steroid with no androgenic effect but a partial
      antiandrogenic effect. The antiovulatory potency of the different progestins
      varies. TMG and NES are the most potent progestins synthesized to date, followed
      by two of the older progestins, keto-desogestrel (keto-DSG) and levonorgestrel
      (LNG). The new molecules TMG, DRSP and DNG also have antiandrogenic activity.
      Striking differences exist regarding the side effects among the progestins and
      the combination with EE leads to other reactions related to the E itself and
      whether the associated progestin counterbalances, more or less, the estrogenic
      action. The 19-norprogesterone molecules and the new molecules DRSP and DNG are
      not androgenic and, therefore, have no negative effect on the lipid profile.
      Given their pharmacological properties, it is likely that the new progestins may
      have neutral effects on metabolic or vascular risks. However, this hypothesis
      must be confirmed in large clinical trials.

PMID- 16291772
TI  - Heart failure therapy: testosterone replacement and its implications.

PMID- 16291773
TI  - Effects of biventricular pacing on interstitial remodelling, tumor necrosis
      factor-alpha expression, and apoptotic death in failing human myocardium.
AB  - AIMS: Recent data from the COMPANION trial have documented that cardiac
      resynchronization therapy (CRT) with biventricular (BiV) pacing reduces mortality
      and hospitalization in patients with advanced CHF, but little is known regarding
      the cellular and molecular mechanisms of CRT. Our aim is to evaluate interstitial
      remodelling, tumor necrosis factor-alpha (TNF-alpha) expression, and apoptosis in
      patients with advanced CHF treated with CRT. METHODS AND RESULTS: We performed
      endomyocardial biopsies in 10 patients, aged 62, with dilated cardiomyopathy
      before and 6 months after the implantation of a BiV pacing device. Clinical
      status and left ventricular (LV) architecture and function were assessed as well
      as myocardial histology, TNF-alpha expression, and apoptotic index. CRT improved
      clinical status, as shown by a significant reduction of the Minnesota living with
      heart failure questionnaire (MLHFQ) score (from 53 to 40) and 6-min walked
      distance (from 290 to 330 m) (all P<0.05 vs. baseline). This was associated with
      reverse LV remodelling substantiated by significant reductions of LV volumes and
      end-systolic circumferential wall stress. Examination of myocardial tissue
      revealed a significant decrease of collagen volume fraction (CVF) (from 25.16 to
      18.0%), TNF-alpha expression (from 9.5 to 3.6 pixel x 10(3)), and apoptotic index
      (from 2030 to 1408 apoptotic nuclei/10(6)), with increased capillary density
      (from 1801 to 2011 capillary/mm(2)) after 6 months of CRT (all P<0.05 vs.
      baseline). Moreover, changes in TNF-alpha expression were positively correlated
      with both CVF and end-systolic circumferential wall stress (r=0.80 and 0.70,
      respectively). CONCLUSION: We provide the first evidence that CRT reduces
      interstitial remodelling, TNF-alpha expression, and apoptosis. The data may
      explain the beneficial effects of CRT on CHF progression and survival.

PMID- 16291774
TI  - Pulmonary toxicity from novel antineoplastic agents.
AB  - BACKGROUND: The pulmonary side-effects induced by novel antineoplastic agents
      have not been well characterized. METHODS: To further investigate this topic,
      relevant English and non-English language studies were identified through
      Medline. For our search we used the generic names of novel cytotoxic or non
      cytotoxic antineoplastic agents and the key phrases pulmonary/lung toxicity,
      dyspnea, pneumonitis, acute lung injury, acute respiratory distress syndrome and
      alveolar damage. The references from the articles identified were reviewed for
      additional sources. Abstracts from International Meetings were also included.
      Furthermore, information was obtained from the Pneumotox website, which provides
      updated knowledge on drug-induced respiratory disease as well as from
      pharmaceutical websites. RESULTS: Most novel antineoplastic drugs may induce
      pulmonary toxicity, which involves mainly the parenchyma, and less frequently the
      airways, pleura or the pulmonary circulation. Furthermore, a subset of these
      agents impairs pulmonary function tests. The exact incidence of lung toxicity
      remains unclear. The most common patterns consist of dyspnea without further
      details and infiltrative lung disease (ILD), denoting changes in the interstitium
      or alveoli. The diagnosis is one of exclusion. ILD is usually benign and responds
      to appropriate treatment; however, fatalities have been reported. CONCLUSIONS:
      Clinicians should be aware of the potential of most novel antineoplastic agents
      to cause lung toxicity. A high index of suspicion is required if these are
      combined with other cytotoxic drugs or radiation.

PMID- 16291775
TI  - Getting the most benefit from the variations research: next steps.
AB  - In this response, I acknowledge the valuable contribution made by John Wennberg
      and colleagues in describing the variations in use rates. I caution against
      reaching certain conclusions based on the limitations of the data, and I offer
      suggested next steps to optimize the benefit to be gained from the study.

PMID- 16291776
TI  - Variations in California hospital regions: another wake-up call for sleeping
      policymakers.
AB  - The paper by John Wennberg and colleagues poses a renewed challenge to federal
      and state policymakers to handle the taxpayers' hard-earned money responsibly--a
      task both have shunned for many decades. With the federal government's deficit
      growing apace and California state's budget, properly accounted for, in deep
      deficit as well, health policymakers can sustain the inefficiencies now apparent
      in our health care system only by pricing more and more low-income Americans out
      of health care. One could question the ethics of that approach.

PMID- 16291777
TI  - Variation in medical care: time for action.
AB  - Variations research has broken new ground by moving analysis of Medicare data
      from the community to the hospital level. The California study of hospitals
      further illustrates the power of comparing performance to demonstrate the levels
      of efficiency that can be achieved. WellPoint, replicating the Dartmouth approach
      with its commercial data, is partnering with medical specialty societies to make
      data "actionable" and move beyond benchmarking to help providers alter practice
      patterns. The shared goal is to achieve a material reduction in practice
      variation throughout health care. Key elements of their partnership include
      establishing national databases, reducing the administrative burden for pay-for
      performance programs and using evidence-based metrics.

PMID- 16291778
TI  - The CMS Quality Roadmap: quality plus efficiency.
AB  - In addition to demonstrating wide variations in costs, resource inputs, and
      quality in California hospitals, John Wennberg and colleagues demonstrate that
      higher quality of care might be associated with increased delivery system
      efficiencies and lower costs. The Centers for Medicare and Medicaid Services
      (CMS) is attempting to address issues raised by Wennberg in implementation of its
      Quality Roadmap. The CMS is actively working with health care stakeholders to
      identify health care efficiency measures, to address opportunities for
      improvement in health care quality and efficiency, and to consider policy
      approaches for reducing regional variation in quality and efficiency.

PMID- 16291779
TI  - Evaluating the efficiency of california providers in caring for patients with
      chronic illnesses.
AB  - In this paper we compare the relative efficiency of health care providers in
      managing patients with severe chronic illnesses over fixed periods of time. To
      minimize the contribution of differences in severity of illness to differences in
      care management, we evaluate performance over fixed intervals prior to death for
      patients who died during a five-year period, 1999-2003. Medicare spending,
      hospital bed and full-time equivalent (FTE) physician inputs, and utilization
      varied extensively between regions, among hospitals located within a given
      region, and among hospitals belonging to a given hospital system. The data point
      to important opportunities to improve efficiency.

PMID- 16291780
TI  - Looking at the U.S. health care system in the rear-view mirror.
AB  - John Wennberg and his colleagues hold up a rear-view mirror on the U.S. health
      care system, reflecting pervasive inconsistencies and showing that more resources
      are not necessarily equivalent to better care. The work shows that although many
      hospitals are investing time and money to improve efficiency, quality, and
      overall patient care, the system is in trouble. Two basic reforms would help
      produce a system that encourages value, with efficient, effective, patient
      centered care. These changes involve how we pay for care and investment in health
      information technology. We should begin by implementing these principles in
      Medicare, the largest U.S. purchaser of care.

PMID- 16291781
TI  - Mode of pollen-tube growth in Pistils of Myrica rubra (Myricaceae): a comparison
      with related families.
AB  - BACKGROUND AND AIMS: It is generally known that fertilization is delayed for more
      than a few weeks after pollination in Fagales. Recent studies showed that, during
      that period, pollen tubes grew in pistils in close association with the
      development of the ovule in a five-step process in Casuarina (Casuarinaceae) and
      a four-step process in Alnus (Betulaceae). The number of pollen tubes was reduced
      from many to one, a fact suggesting that delayed fertilization plays a role for
      gametophyte selection. Myrica (Myricaceae) also shows delayed fertilization for
      >2 weeks after pollination, but nothing is known of how pollen tubes grow in the
      pistil during that period. METHODS: Pollen-tube growth and the development of the
      ovule in pistils was investigated by fluorescent and scanning electron microscopy
      and analysis of microtome sections of the pistils. KEY RESULTS: Developmental
      study of the pollen-tube growth in the pistil of M. rubra showed that the tip of
      the pollen tube was branched or lay in a zigzag pattern in the upper space of the
      ovarian locule or near the tip of the integument, and subsequently was swollen on
      the nucellar surface. Such morphological changes indicate that the pollen-tube
      growth was temporarily arrested before fertilization. The pollen-tube growth in
      M. rubra can therefore be summarized as occurring in three steps: (1) from the
      stigma to the ovarian locule; (2) from the ovarian locule to the nucellar
      surface; and (3) from the nucellar surface to the embryo sac. CONCLUSION: Myrica
      differs from other families in that the pollen tubes arrest their growth on the
      nucellar surface, probably digesting nutrient from nucellar cells. There is
      little information on five other families of Fagales. An extensive study is
      needed to better understand the diversity and function of the mode of pollen-tube
      growth within the order.

PMID- 16291782
TI  - Changes in growth and nutrient uptake in Brassica oleracea exposed to atmospheric
      ammonia.
AB  - BACKGROUND AND AIMS: Plant shoots form a sink for NH3, and are able to utilize it
      as a source of N. NH3 was used as a tool to investigate the interaction between
      foliar N uptake and root N uptake. To what extent NH3 can contribute to the N
      budget of the plant or can be regarded as a toxin, was investigated in relation
      to its concentration and the N supply in the root environment. METHODS: Brassica
      oleracea was exposed to 0, 4 and 8 microL L(-1) NH3, with and without nitrate in
      the nutrient solution. Growth, N compounds, nitrate uptake rate, soluble sugars
      and cations were measured. KEY RESULTS: In nitrate-sufficient plants, biomass
      production was not affected at 4 microL L(-1) NH3, but was reduced at 8 microL L(
      1) NH3. In nitrate-deprived plants, shoot biomass was increased at both
      concentrations, but root biomass decreased at 8 microL L(-1) NH3. The measured
      nitrate uptake rates agreed well with the plant's N requirement for growth. In
      nitrate-sufficient plants nitrate uptake at 4 and 8 microL L(-1) NH3 was reduced
      by 50 and 66 %, respectively. CONCLUSIONS: The present data do not support the
      hypothesis that NH3 toxicity is caused by a shortage of sugars or a lack of
      capacity to detoxify NH3. It is unlikely that amino acids, translocated from the
      shoot to root, are the signal metabolites involved in the down-regulation of
      nitrate uptake, since no relationship was found between changes in nitrate uptake
      and root soluble N content of NH3-exposed plants.

PMID- 16291783
TI  - FRIGIDA-ESSENTIAL 1 interacts genetically with FRIGIDA and FRIGIDA-LIKE 1 to
      promote the winter-annual habit of Arabidopsis thaliana.
AB  - Studies of natural variation have revealed that the winter-annual habit of many
      accessions of Arabidopsis is conferred by two genes, FRIGIDA (FRI) and FLOWERING
      LOCUS C (FLC), whose activities impose a vernalization requirement. To better
      understand the mechanism underlying the winter-annual habit, a genetic screen was
      performed to identify mutants that suppress the late-flowering behavior of a non
      vernalized winter-annual strain. We have identified a locus, FRIGIDA-ESSENTIAL 1
      (FES1), which, like FRI, is specifically required for the upregulation of FLC
      expression. FES1 is predicted to encode a protein with a CCCH zinc finger, but
      the predicted sequence does not otherwise share significant similarity with other
      known proteins. fes1 is a complete suppressor of FRI-mediated delayed flowering,
      but has little effect on the late-flowering phenotype of autonomous-pathway
      mutants. Thus, FES1 activity is required for the FRI-mediated winter-annual
      habit, but not for the similar phenotype resulting from autonomous-pathway
      mutations. Epistasis analysis between FES1, FRI and another specific suppressor
      of FRI-containing lines, FRIGIDA-LIKE 1 (FRL1), indicates that these genes do not
      function in a linear pathway, but instead act cooperatively to promote the
      expression of FLC.

PMID- 16291784
TI  - Ptf1a determines GABAergic over glutamatergic neuronal cell fate in the spinal
      cord dorsal horn.
AB  - Mutations in the human and mouse PTF1A/Ptf1a genes result in permanent diabetes
      mellitus and cerebellar agenesis. We show that Ptf1a is present in precursors to
      GABAergic neurons in spinal cord dorsal horn as well as the cerebellum. A null
      mutation in Ptf1a reveals its requirement for the dorsal horn GABAergic neurons.
      Specifically, Ptf1a is required for the generation of early-born (dI4, E10.5) and
      late-born (dIL(A), E12.5) dorsal interneuron populations identified by
      homeodomain factors Lhx1/5 and Pax2. Furthermore, in the absence of Ptf1a, the
      dI4 dorsal interneurons trans-fate to dI5 (Lmx1b(+)), and the dIL(A) to dIL(B)
      (Lmx1b(+);Tlx3(+)). This mis-specification of neurons results in a complete loss
      of inhibitory GABAergic neurons and an increase in the excitatory glutamatergic
      neurons in the dorsal horn of the spinal cord by E16.5. Thus, Ptf1a function is
      essential for GABAergic over glutamatergic neuronal cell fates in the developing
      spinal cord, and provides an important genetic link between inhibitory and
      excitatory interneuron development.

PMID- 16291785
TI  - A novel C. elegans zinc finger transcription factor, lsy-2, required for the cell
      type-specific expression of the lsy-6 microRNA.
AB  - The two Caenorhabditis elegans gustatory neurons, ASE left (ASEL) and ASE right
      (ASER) are morphologically bilaterally symmetric, yet left/right asymmetric in
      function and in the expression of specific chemosensory signaling molecules. The
      ASEL versus ASER cell-fate decision is controlled by a complex gene regulatory
      network composed of microRNAs (miRNAs) and transcription factors. Alterations in
      the activities of each of these regulatory factors cause a complete lateral cell
      fate switch. Here, we describe lsy-2, a novel C2H2 zinc finger transcription
      factor that is required for the execution of the ASEL stable state. In lsy-2 null
      mutants, the ASEL neuron adopts the complete ASER gene expression profile,
      including both upstream regulatory and terminal effector genes. The normally
      left/right asymmetric ASE neurons are therefore ;symmetrized' in lsy-2 mutants.
      Cell-specific rescue experiments indicate that lsy-2 is required autonomously in
      ASEL for the activation of ASEL-specifying factors and the repression of ASER
      specifying factors. Genetic epistasis experiments demonstrate that lsy-2 exerts
      its activity by regulating the transcription of the lsy-6 miRNA in the ASEL
      neuron, thereby making lsy-2 one of the few factors known to control the cell
      type specificity of miRNA gene expression.

PMID- 16291786
TI  - The RNA-binding protein Squid is required for the establishment of
      anteroposterior polarity in the Drosophila oocyte.
AB  - The heterogeneous nuclear ribonucleoprotein (hnRNP) Squid (Sqd) is a highly
      abundant protein that is expected to bind most cellular RNAs. Nonetheless, Sqd
      plays a very specific developmental role in dorsoventral (DV) axis formation
      during Drosophila oogenesis by localizing gurken (grk) RNA. Here, we report that
      Sqd is also essential for anteroposterior (AP) axis formation. We identified sqd
      in a screen for modifiers of the Protein Kinase A (PKA) oogenesis polarity
      phenotype. The AP defects of sqd mutant oocytes resemble those of PKA mutants in
      several ways. In both cases, the cytoskeletal reorganization at mid-oogenesis,
      which depends on a signal from the posterior follicle cells, does not produce a
      correctly polarized microtubule (MT) network. This causes the posterior
      determinant, oskar (osk) RNA, to localize to central regions of the oocyte, where
      it is ectopically translated. Additionally, MT-dependent anterior movement of the
      oocyte nucleus and the grk-dependent specification of posterior follicle cells
      are unaffected in both mutants. However, in contrast to PKA mutants, sqd mutants
      do not retain a discrete posterior MT organizing center (MTOC) capable of
      supporting ectopic posterior localization of bicoid (bcd) RNA. sqd mutants also
      display several other phenotypes not seen in PKA mutants; these probably result
      from the disruption of MT polarity in earlier stages of oogenesis. Loss of Sqd
      does not affect polarity in follicle cells, wings or eyes, indicating a specific
      role in the determination of MT polarity within the germline.

PMID- 16291787
TI  - A role for foxd3 and sox10 in the differentiation of gonadotropin-releasing
      hormone (GnRH) cells in the zebrafish Danio rerio.
AB  - Gonadotropin-releasing hormone (GnRH) is found in a wide range of vertebrate
      tissues, including the nervous system. In general, GnRH has two functions:
      endocrine, acting as a releasing hormone; and neuromodulatory, affecting neural
      activity in the peripheral and central nervous system. The best understood
      population of GnRH cells is that of the hypothalamus, which is essential for
      reproduction. Less well understood are the populations of GnRH cells found in the
      terminal nerve and midbrain, which appear to be neuromodulatory in function. The
      GnRH-containing cells of the midbrain are proposed to arise from the
      mesencephalic region of the neural tube. Previously, we showed that
      neuromodulatory GnRH cells of the terminal nerve arise from cranial neural crest.
      To test the hypothesis that neuromodulatory GnRH cells of the midbrain also arise
      from neural crest, we used gene knockdown experiments in zebrafish to disrupt
      neural crest development. We demonstrate that decrement of the function of foxd3
      and/or sox10, two genes important for the development and specification of neural
      crest, resulted in a reduction and/or loss of GnRH cells of the midbrain, as well
      as a reduction in the number of terminal nerve GnRH cells. Therefore, our data
      support a neural crest origin for midbrain GnRH cells. Additionally, we
      demonstrate that knockdown of kallmann gene function resulted in the loss of
      endocrine GnRH cells of the hypothalamus, but not of neuromodulatory GnRH cells
      of the midbrain and terminal nerve, thus providing additional evidence for
      separate pathways controlling the development of neuromodulatory and endocrine
      GnRH cells.

PMID- 16291788
TI  - Non-cell-autonomous role for Cripto in axial midline formation during vertebrate
      embryogenesis.
AB  - Several membrane-associated proteins are known to modulate the activity and range
      of potent morphogenetic signals during development. In particular, members of the
      EGF-CFC family encode glycosyl-phosphatidylinositol (GPI)-linked proteins that
      are essential for activity of the transforming growth factor beta (TGFbeta)
      ligand Nodal, a factor that plays a central role in establishing the vertebrate
      body plan. Genetic and biochemical studies have indicated that EGF-CFC proteins
      function as cell-autonomous co-receptors for Nodal; by contrast, cell culture
      data have suggested that the mammalian EGF-CFC protein Cripto can act as a
      secreted signaling factor. Here we show that Cripto acts non-cell-autonomously
      during axial mesendoderm formation in the mouse embryo and may possess
      intercellular signaling activity in vivo. Phenotypic analysis of hypomorphic
      mutants demonstrates that Cripto is essential for formation of the notochordal
      plate, prechordal mesoderm and foregut endoderm during gastrulation. Remarkably,
      Cripto null mutant cells readily contribute to these tissues in chimeras,
      indicating non-cell-autonomy. Consistent with these loss-of-function analyses,
      gain-of-function experiments in chick embryos show that exposure of node/head
      process mesoderm to soluble Cripto protein results in alterations in cell fates
      toward anterior mesendoderm, in a manner that is dependent on Nodal signaling.
      Taken together, our findings support a model in which Cripto can function in
      trans as an intercellular mediator of Nodal signaling activity.

PMID- 16291789
TI  - Distinct roles for Xenopus Tcf/Lef genes in mediating specific responses to
      Wnt/beta-catenin signalling in mesoderm development.
AB  - Tcf/Lef transcription factors and beta-catenin mediate canonical Wnt signalling,
      which plays remarkably diverse roles in embryonic development, stem cell renewal
      and cancer progression. To investigate the molecular mechanisms allowing for
      these diverse yet specific functions, we studied the several distinct roles for
      Wnt/beta-catenin signalling in early Xenopus development: establishing the dorsal
      body axis; regulating mesoderm induction; and subsequent ventrolateral
      patterning. Our previous experiments and the expression patterns of Tcf/Lef
      factors during these embryonic stages led us to examine whether different Tcf/Lef
      factors mediate these distinct events downstream of canonical Wnt/beta-catenin
      signalling. By manipulating gene expression with morpholino-driven gene knockdown
      and capped RNA-mediated rescue, we show that genes encoding different Tcf/Lef
      transcription factors mediate distinct responses to Wnt signalling in early
      Xenopus development: Tcf1 and Tcf3 genes are non-redundantly required in mesoderm
      induction for mediating primarily transcriptional activation and repression,
      respectively; while ventrolateral patterning requires both Tcf1 and Lef1 genes to
      express sufficient levels of transcription-activating Tcf factors. Our
      investigation further identifies that motifs within their central domain, rather
      than their C-terminus, determine the particular molecular function of Tcf/Lef
      factors. These findings suggest that Tcf/Lef genes encode factors of different
      activities, which function together in antagonistic or synergistic ways to
      modulate the intensity and outcome of Wnt/beta-catenin signalling and to trigger
      tissue-specific responses.

PMID- 16291790
TI  - Wnt3a links left-right determination with segmentation and anteroposterior axis
      elongation.
AB  - The alignment of the left-right (LR) body axis relative to the anteroposterior
      (AP) and dorsoventral (DV) axes is central to the organization of the vertebrate
      body plan and is controlled by the node/organizer. Somitogenesis plays a key role
      in embryo morphogenesis as a principal component of AP elongation. How
      morphogenesis is coupled to axis specification is not well understood. We
      demonstrate that Wnt3a is required for LR asymmetry. Wnt3a activates the
      Delta/Notch pathway to regulate perinodal expression of the left determinant
      Nodal, while simultaneously controlling the segmentation clock and the molecular
      oscillations of the Wnt/beta-catenin and Notch pathways. We provide evidence that
      Wnt3a, expressed in the primitive streak and dorsal posterior node, acts as a
      long-range signaling molecule, directly regulating target gene expression
      throughout the node and presomitic mesoderm. Wnt3a may also modulate the symmetry
      breaking activity of mechanosensory cilia in the node. Thus, Wnt3a links the
      segmentation clock and AP axis elongation with key left-determining events,
      suggesting that Wnt3a is an integral component of the trunk organizer.

PMID- 16291791
TI  - Growth and cell survival are unevenly impaired in pixie mutant wing discs.
AB  - It is largely unknown how growth slows and then stops in vivo. Similar to most
      organs, Drosophila imaginal discs undergo a fast, near-exponential growth phase
      followed by a slow growth phase before final target size is reached. We have used
      a genetic approach to study the role of an ABC-E protein, Pixie, in wing disc
      growth. pixie mutants, like mutants in ribosomal proteins genes (known as
      Minutes), show severe developmental delay with relatively mild alterations in
      final body size. Intriguingly, pixie mutant wing imaginal discs show complex
      regional and temporal defects in growth and cell survival that are compensated to
      result in near-normal final size. In S2 cells, Pixie, like its yeast homolog
      RLI1, is required for translation. However, a comparison of the growth of
      eukaryotic translation initiation factor eIF4A and pixie mutant clones in wing
      discs suggests that only a subset of translation regulators, including pixie,
      mediate regional differences in growth and cell survival in wing discs.
      Interestingly, some of the regional effects on pixie mutant clone growth are
      enhanced in a Minute background. Our results suggest that the role of Pixie is
      not merely to allow growth, as might be expected for a translation regulator.
      Instead, Pixie also behaves as a target of putative constraining signals that
      slow disc growth during late larval life. We propose a model in which a balance
      of growth inhibitors and promoters determines tissue growth rates and cell
      survival. An alteration in this balance slows growth before final disc size is
      reached.

PMID- 16291792
TI  - Arrow (LRP6) and Frizzled2 cooperate to degrade Wingless in Drosophila imaginal
      discs.
AB  - Lysosome-mediated ligand degradation is known to shape morphogen gradients and
      modulate the activity of various signalling pathways. We have investigated the
      degradation of Wingless, a Drosophila member of the Wnt family of secreted growth
      factors. We find that one of its signalling receptors, Frizzled2, stimulates
      Wingless internalization both in wing imaginal discs and cultured cells. However,
      this is not sufficient for degradation. Indeed, as shown previously,
      overexpression of Frizzled2 leads to Wingless stabilization in wing imaginal
      discs. We show that Arrow (the Drosophila homologue of LRP5/6), another receptor
      involved in signal transduction, abrogates such stabilization. We provide
      evidence that Arrow stimulates the targeting of Frizzled2-Wingless (but not Dally
      like-Wingless) complexes to a degradative compartment. Thus, Frizzled2 alone
      cannot lead Wingless all the way from the plasma membrane to a degradative
      compartment. Overall, Frizzled2 achieves ligand capture and internalization,
      whereas Arrow, and perhaps downstream signalling, are essential for lysosomal
      targeting.

PMID- 16291793
TI  - Sim1 and Sim2 are required for the correct targeting of mammillary body axons.
AB  - The mammillary body (MB), and its axonal projections to the thalamus
      (mammillothalamic tract, MTT) and the tegmentum (mammillotegmental tract, MTEG),
      are components of a circuit involved in spatial learning. The bHLH-PAS
      transcription factors SIM1 and SIM2 are co-expressed in the developing MB. We
      have found that MB neurons are generated and that they survive at least until
      E18.5 in embryos lacking both Sim1 and Sim2 (Sim1(-/-);Sim2(-/-)). However, the
      MTT and MTEG are histologically absent in Sim1(-/-);Sim2(-/-) embryos, and are
      reduced in embryos lacking Sim1 but bearing one or two copies of Sim2, indicating
      a contribution of the latter to the development of MB axons. We have generated,
      by homologous recombination, a null allele of Sim1 (Sim1(tlz)) in which the tau
      lacZ fusion gene was introduced, allowing the staining of MB axons. Consistent
      with the histological studies, lacZ staining showed that the MTT/MTEG is barely
      detectable in Sim1(tlz/tlz);Sim2(+/-) and Sim1(tlz/tlz);Sim2(-/-) brains.
      Instead, MB axons are splayed and grow towards the midline. Slit1 and Slit2,
      which code for secreted molecules that induce the repulsion of ROBO1-producing
      axons, are expressed in the midline at the level of the MB, whereas Robo1 is
      expressed in the developing MB. The expression of Rig-1/Robo3, a negative
      regulator of Slit signalling, is upregulated in the prospective MB of Sim1/Sim2
      double mutants, raising the possibility that the growth of mutant MB axons
      towards the midline is caused by a decreased sensitivity to SLIT. Finally, we
      found that Sim1 and Sim2 act along compensatory, but not hierarchical, pathways,
      suggesting that they play similar roles in vivo.

PMID- 16291794
TI  - Cell-to-cell movement of the CAPRICE protein in Arabidopsis root epidermal cell
      differentiation.
AB  - CAPRICE (CPC), a small, R3-type Myb-like protein, is a positive regulator of root
      hair development in Arabidopsis. Cell-to-cell movement of CPC is important for
      the differentiation of epidermal cells into trichoblasts (root hair cells). CPC
      is transported from atrichoblasts (hairless cells), where it is expressed, to
      trichoblasts, and generally accumulates in their nuclei. Using truncated versions
      of CPC fused to GFP, we identified a signal domain that is necessary and
      sufficient for CPC cell-to-cell movement. This domain includes the N-terminal
      region and a part of the Myb domain. Amino acid substitution experiments
      indicated that W76 and M78 in the Myb domain are critical for targeted transport,
      and that W76 is crucial for the nuclear accumulation of CPC:GFP. To evaluate the
      tissue-specificity of CPC movement, CPC:GFP was expressed in the stele using the
      SHR promoter and in trichoblasts using the EGL3 promoter. CPC:GFP was able to
      move from trichoblasts to atrichoblasts but could not exit from the stele,
      suggesting the involvement of tissue-specific regulatory factors in the
      intercellular movement of CPC. Analyses with a secretion inhibitor, Brefeldin A,
      and with an rhd3 mutant defective in the secretion process in root epidermis
      suggested that intercellular CPC movement is mediated through plasmodesmata.
      Furthermore, the fusion of CPC to tandem-GFPs defined the capability of CPC to
      increase the size exclusion limit of plasmodesmata.

PMID- 16291795
TI  - Angioblast-mesenchyme induction of early kidney development is mediated by Wt1
      and Vegfa.
AB  - Most studies on kidney development have considered the interaction of the
      metanephric mesenchyme and the ureteric bud to be the major inductive event that
      maintains tubular differentiation and branching morphogenesis. The mesenchyme
      produces Gdnf, which stimulates branching, and the ureteric bud stimulates
      continued growth of the mesenchyme and differentiation of nephrons from the
      induced mesenchyme. Null mutation of the Wt1 gene eliminates outgrowth of the
      ureteric bud, but Gdnf has been identified as a target of Pax2, but not of Wt1.
      Using a novel system for microinjecting and electroporating plasmid expression
      constructs into murine organ cultures, it has been demonstrated that Vegfa
      expression in the mesenchyme is regulated by Wt1. Previous studies had identified
      a population of Flk1-expressing cells in the periphery of the induced mesenchyme,
      and adjacent to the stalk of the ureteric bud, and that Vegfa was able to
      stimulate growth of kidneys in organ culture. Here it is demonstrated that
      signaling through Flk1 is required to maintain expression of Pax2 in the
      mesenchyme of the early kidney, and for Pax2 to stimulate expression of Gdnf.
      However, once Gdnf stimulates branching of the ureteric bud, the Flk1-dependent
      angioblast signal is no longer required to maintain branching morphogenesis and
      induction of nephrons. Thus, this work demonstrates the presence of a second set
      of inductive events, involving the mesenchymal and angioblast populations,
      whereby Wt1-stimulated expression of Vegfa elicits an as-yet-unidentified signal
      from the angioblasts, which is required to stimulate the expression of Pax2 and
      Gdnf, which in turn elicits an inductive signal from the ureteric bud.

PMID- 16291796
TI  - The roles of FGF signaling in germ cell migration in the mouse.
AB  - Fibroblast growth factor (FGF) signaling is thought to play a role in germ cell
      behavior. FGF2 has been reported to be a mitogen for primordial germ cells in
      vitro, whilst combinations of FGF2, steel factor and LIF cause cultured germ
      cells to transform into permanent lines of pluripotent cells resembling ES cells.
      However, the actual function of FGF signaling on the migrating germ cells in vivo
      is unknown. We show, by RT-PCR analysis of cDNA from purified E10.5 germ cells,
      that germ cells express two FGF receptors: Fgfr1-IIIc and Fgfr2-IIIb. Second, we
      show that FGF-mediated activation of the MAP kinase pathway occurs in germ cells
      during their migration, and thus they are potentially direct targets of FGF
      signaling. Third, we use cultured embryo slices in simple gain-of-function
      experiments, using FGF ligands, to show that FGF2, a ligand for FGFR1-IIIc,
      affects motility, whereas FGF7, a ligand for FGFR2-IIIb, affects germ cell
      numbers. Loss of function, using a specific inhibitor of FGF signaling, causes
      increased apoptosis and inhibition of cell shape change in the migrating germ
      cells. Lastly, we confirm in vivo the effects seen in slice cultures in vitro, by
      examining germ cell positions and numbers in embryos carrying a loss-of-function
      allele of FGFR2-IIIb. In FGFR2-IIIb(-/-) embryos, germ cell migration is
      unaffected, but the numbers of germ cells are significantly reduced. These data
      show that a major role of FGF signaling through FGFR2-IIIb is to control germ
      cell numbers. The data do not discriminate between direct and indirect effects of
      FGF signaling on germ cells, and both may be involved.

PMID- 16291797
TI  - Photosynthetic consequences of phenotypic plasticity in response to submergence:
      Rumex palustris as a case study.
AB  - Survival and growth of terrestrial plants is negatively affected by complete
      submergence. This is mainly the result of hampered gas exchange between plants
      and their environment, since gas diffusion is severely reduced in water compared
      with air, resulting in O2 deficits which limit aerobic respiration. The
      continuation of photosynthesis could probably alleviate submergence-stress in
      terrestrial plants, but its potential under water will be limited as the
      availability of CO2 is hampered. Several submerged terrestrial plant species,
      however, express plastic responses of the shoot which may reduce gas diffusion
      resistance and enhance benefits from underwater photosynthesis. In particular,
      the plasticity of the flooding-tolerant terrestrial species Rumex palustris
      turned out to be remarkable, making it a model species suitable for the study of
      these responses. During submergence, the morphology and anatomy of newly
      developed leaves changed: 'aquatic' leaves were thinner and had thinner cuticles.
      As a consequence, internal O2 concentrations and underwater CO2 assimilation
      rates were higher at the prevailing low CO2 concentrations in water. Compared
      with heterophyllous amphibious plant species, underwater photosynthesis rates of
      terrestrial plants may be very limited, but the effects of underwater
      photosynthesis on underwater survival are impressive. A combination of recently
      published data allowed quantification of the magnitude of the acclimation
      response in this species. Gas diffusion resistance in terrestrial leaves
      underwater was about 15,000 times higher than in air. Strikingly, acclimation to
      submergence reduced this factor to 400, indicating that acclimated leaves of R.
      palustris had an approximately 40 times lower gas diffusion resistance than non
      acclimated ones.

PMID- 16291798
TI  - In vivo imaging of MADS-box transcription factor interactions.
AB  - MADS-box transcription factors are major regulators of development in flowering
      plants. The factors act in a combinatorial manner, either as homo- or
      heterodimers, and they control floral organ formation and identity and many other
      developmental processes through a complex network of protein-protein and protein
      DNA interactions. Despite the fact that many studies have been carried out to
      elucidate MADS-box protein dimerization by yeast systems, very little information
      is available on the behaviour of these molecules in planta. Here, evidence for
      specific interactions between the petunia MADS-box proteins FBP2, FBP11, and
      FBP24 is provided in vivo. The dimers identified in yeast for the ovule-specific
      FBP24 protein have been confirmed in living plant cells by means of fluorescence
      resonance energy transfer-fluorescence lifetime imaging microscopy and, in
      addition, some of the most likely, less stable homo- and heterodimers were
      identified. This in vivo approach revealed that particular dimers could only be
      detected in specific sub-nuclear domains. In addition, evidence for the in planta
      assembly of these ovule-specific MADS-box transcription factors into higher-order
      complexes is provided.

PMID- 16291799
TI  - CK2 phosphorylation weakens 90 kDa MFP1 association to the nuclear matrix in
      Allium cepa.
AB  - MFP1 is a conserved plant coiled-coil protein located on the stroma side of the
      chloroplast thylakoids, as well as in the nuclear matrix. It displays species
      specific variability in the number of genes, proteins, and expression. Allium
      cepa has two nuclear proteins antigenically related to MFP1 with different M(r),
      pI, distribution, and expression, but only the 90 kDa MFP1 protein is a nuclear
      matrix component that associates with both the nucleoskeletal filaments and a new
      category of nuclear bodies. The 90 kDa AcMFP1 migrates in two-dimensional blots
      as two sets of spots. The hypo-phosphorylated forms (pI approximately 9.5) are
      tightly bound to the nuclear matrix, while high ionic strength buffers release
      the more acidic hyper-phosphorylated ones (pI approximately 8.5), suggesting that
      the protein is post-translationally modified, and that these modifications
      control its attachment to the nuclear matrix. Dephosphorylation by exogenous
      alkaline phosphatase and phosphorylation by exogenous CK2, as well as specific
      inhibition and stimulation of endogenous CK2 with heparin and spermine and
      spermidine, respectively, revealed that the protein is an in vitro and in vivo
      substrate of this enzyme, and that CK2 phosphorylation weakens the strength of
      its binding to the nuclear matrix. In synchronized cells, the nuclear 90 kDa
      AcMFP1 phosphorylation levels vary during the cell cycle with a moderate peak in
      G2. These results provide the first evidence for AcMFP1 in vivo phosphorylation,
      and open up further research on its nuclear functions.

PMID- 16291800
TI  - A root- and hypocotyl-specific gene coding for copper-containing amine oxidase is
      related to cell expansion in soybean seedlings.
AB  - Polyamines are considered to participate in various processes of plant
      development. In this study, the possible implication of putrescine catabolism by
      the copper-containing amine oxidases (CuAOs, EC 1.4.3.6) in the development of
      roots and hypocotyls was examined. For this purpose, two cDNA clones of Glycine
      max (L.) Merr. cv. Williams, designated as GmCuAO1 and GmCuAO2, exhibiting
      extensive similarity with previously characterized CuAO clones from other plants,
      have been isolated and characterized. The expression of the GmCuAO1 gene is root-
      and hypocotyl-specific, while GmCuAO2 seems not to be expressed in a tissue
      specific manner. Moreover, the GmCuAO1 gene is predominantly expressed in tissues
      which are characterized by rapid extension growth, such as the apical segments of
      etiolated hypocotyls. Using convex and concave segments of the etiolated
      hypocotyl apical hook it has been demonstrated that GmCuAO1 is strongly expressed
      in expanding cells of the concave part when exposed to light, while the same
      pattern is also followed by the activity of enzymes involved in putrescine
      catabolism. In dark and photoperiodically grown hypocotyls, activity measurements
      of the enzymes involved in putrescine catabolism have shown that the activity of
      these enzymes is several-fold higher in rapidly growing tissues. Furthermore, the
      cellular and tissue distribution of GmCuAO1 gene transcripts in the root axis and
      in hypocotyls confirmed their abundance in developing tissues and expanding
      cells. The results provide evidence suggesting that a tissue-specific gene coding
      for CuAO is correlated with cell expansion in fast-growing tissues of root and
      hypocotyls.

PMID- 16291801
TI  - Effects of genetic manipulation of alcohol dehydrogenase levels on the response
      to stress and the synthesis of secondary metabolites in grapevine leaves.
AB  - The functional role of Adh in regulating susceptibility to abiotic stress and the
      synthesis of secondary metabolites was investigated in transgenic grapevine
      plants over- and underexpressing alcohol dehydrogenase (Adh). Plants were
      transformed with gene constructs containing a sense or antisense orientated
      grapevine VvAdh2 cDNA under the constitutive cauliflower mosaic virus 35S
      promoter. Plants transformed with either antisense orientation or the Adh-less
      construct displayed a low but detectable constitutive ADH activity, whereas
      plants transformed with the sense-expressed transgene showed a significantly
      higher (100-fold) ADH activity than the control. Compared with the control, the
      sense transgene induced an overexpression of VvAdh2 transcripts, whereas a
      reduced VvAdh2 expression was detected in antisense transformants. Grapevine
      plants overexpressing Adh displayed a lower sucrose content, a higher degree of
      polymerization of proanthocyanidins, and a generally increased content of
      volatile compounds, mainly in carotenoid- and shikimate-derived volatiles. In
      general, no significant differences between sense/antisense transformants were
      observed with regard to carotenoid and chlorophyll contents, suggesting a strong
      metabolic regulation of the synthesis of these compounds.

PMID- 16291802
TI  - Directional selectivity of BOLD activity in human posterior parietal cortex for
      memory-guided double-step saccades.
AB  - We used functional magnetic resonance imaging (fMRI) to investigate the role of
      the human posterior parietal cortex (PPC) in storing target locations for delayed
      double-step saccades. To do so, we exploited the laterality of a subregion of PPC
      that preferentially responds to the memory of a target location presented in the
      contralateral visual field. Using an event-related design, we tracked fMRI signal
      changes in this region while subjects remembered the locations of two
      sequentially flashed targets, presented in either the same or different visual
      hemifields, and then saccaded to them in sequence. After presentation of the
      first target, the fMRI signal was always related to the side of the visual field
      in which it had been presented. When the second target was added, the cortical
      activity depended on the respective locations of both targets but was still
      significantly selective for the target of the first saccade. We conclude that
      this region within the human posterior parietal cortex not only acts as spatial
      storage center by retaining target locations for subsequent saccades but is also
      involved in selecting the target for the first intended saccade.

PMID- 16291803
TI  - Bistable behavior originating in the axon of a crustacean motor neuron.
AB  - Both vertebrate and invertebrate motor neurons can display bistable behavior in
      which self-sustained tonic firing results from a brief excitatory stimulus.
      Induction of the bistability is usually dependent on activation of intrinsic
      conductances located in the somatodendritic area and is commonly sensitive to
      action of neuromodulators. We have observed bistable behavior in a neuromuscular
      preparation from the foregut of the crab Cancer borealis that consists of the
      gastric mill 4 (gm4) muscle and the nerve that innervates it, the dorsal gastric
      nerve (dgn). Nerve-evoked contractions of enhanced amplitude and long duration
      (>30 s) were induced by extracellular stimulation when the stimulus voltage was
      above a certain threshold. Intracellular and extracellular recordings showed that
      the large contractions were accompanied by persistent firing of the dorsal
      gastric (DG) motor neuron that innervates gm4. The persistent firing could be
      induced only by stimulating a specific region of the axon and could not be
      triggered by depolarizing the soma, even at current amplitudes that induced high
      frequency firing of the neuron. The bistable behavior was abolished in low-Ca2+
      saline or when nicardipine or flufenamic acid, blockers of L-type Ca2+ and Ca2+
      activated nonselective cation currents, respectively, was applied to the axonal
      stimulation region of the dgn. Negative immunostaining for synapsin and
      synaptotagmin argued against the presence of synaptic/modulatory neuropil in the
      dgn. Collectively, our results suggest that bistable behavior in a motor neuron
      can originate in the axon and may not require the action of a locally released
      neuromodulator.

PMID- 16291804
TI  - Gap junctions between accessory medulla neurons appear to synchronize circadian
      clock cells of the cockroach Leucophaea maderae.
AB  - The temporal organization of physiological and behavioral states is controlled by
      circadian clocks in apparently all eukaryotic organisms. In the cockroach
      Leucophaea maderae lesion and transplantation studies located the circadian
      pacemaker in the accessory medulla (AMe). The AMe is densely innervated by gamma
      aminobutyric acid (GABA)-immunoreactive and peptidergic neurons, among them the
      pigment-dispersing factor immunoreactive circadian pacemaker candidates. The
      large majority of cells of the cockroach AMe spike regularly and synchronously in
      the gamma frequency range of 25-70 Hz as a result of synaptic and nonsynaptic
      coupling. Although GABAergic coupling forms assemblies of phase-locked cells, in
      the absence of synaptic release the cells remain synchronized but fire now at a
      stable phase difference. To determine whether these coupling mechanisms of AMe
      neurons, which are independent of synaptic release, are based on electrical
      synapses between the circadian pacemaker cells the gap-junction blockers
      halothane, octanol, and carbenoxolone were used in the presence and absence of
      synaptic transmission. Here, we show that different populations of AMe neurons
      appear to be coupled by gap junctions to maintain synchrony at a stable phase
      difference. This synchronization by gap junctions is a prerequisite to phase
      locked assembly formation by synaptic interactions and to synchronous gamma-type
      action potential oscillations within the circadian clock.

PMID- 16291805
TI  - Spatial updating in area LIP is independent of saccade direction.
AB  - We explore the world around us by making rapid eye movements to objects of
      interest. Remarkably, these eye movements go unnoticed, and we perceive the world
      as stable. Spatial updating is one of the neural mechanisms that contributes to
      this perception of spatial constancy. Previous studies in macaque lateral
      intraparietal cortex (area LIP) have shown that individual neurons update, or
      "remap," the locations of salient visual stimuli at the time of an eye movement.
      The existence of remapping implies that neurons have access to visual information
      from regions far beyond the classically defined receptive field. We hypothesized
      that neurons have access to information located anywhere in the visual field. We
      tested this by recording the activity of LIP neurons while systematically varying
      the direction in which a stimulus location must be updated. Our primary finding
      is that individual neurons remap stimulus traces in multiple directions,
      indicating that LIP neurons have access to information throughout the visual
      field. At the population level, stimulus traces are updated in conjunction with
      all saccade directions, even when we consider direction as a function of
      receptive field location. These results show that spatial updating in LIP is
      effectively independent of saccade direction. Our findings support the hypothesis
      that the activity of LIP neurons contributes to the maintenance of spatial
      constancy throughout the visual field.

PMID- 16291806
TI  - Contralateral hemimicrencephaly and clinical-pathological correlations in
      children with hemimegalencephaly.
AB  - In paediatric epilepsy surgery patients with hemimegalencephaly (HME; n = 23),
      this study compared clinical, neuroimaging and pathologic features to discern
      potential mechanisms for suboptimal post-hemispherectomy developmental outcomes
      and structural pathogenesis. MRI measured affected and non-affected cerebral
      hemisphere volumes for HME and non-HME cases, including monozygotic twins where
      one sibling had HME. Staining against neuronal nuclei (NeuN) determined grey and
      white matter cell densities and sizes in HME and autopsy cases, including the non
      affected side of a HME surgical/autopsy case. By MRI, the affected hemisphere was
      larger and the non-affected side smaller in HME compared with non-HME children.
      The affected HME side showed enlarged abnormal deep grey and white matter
      structures and/or T2-weighted hypointensity in the subcortical white matter in
      75% of cases, suggestive of excessive pre-natal neurogenesis and heterotopias.
      Histopathological examination of the affected HME side revealed immature
      appearing neurons in 70%, polymicrogyria (PMG) in 61% and balloon cells in 45% of
      cases. Compared with autopsy cases, in HME children NeuN cell densities on the
      affected side were increased in the molecular layer and upper cortex (+244 to
      +18%), decreased in lower cortical layers (-35%) and increased in the white
      matter (+139 to +149%). Deep grey matter MRI abnormalities and/or T2-weighted
      white matter hypointensity correlated with the presence of immature-appearing
      neurons and PMG on histopathology, decreased NeuN cell densities in lower
      cortical layers and a positive history of infantile spasms. Post-surgery seizure
      control was associated with decreased NeuN densities in the molecular layer. In
      young children with HME and epilepsy, these findings indicate that there are
      bilateral cerebral hemispheric abnormalities and contralateral hemimicrencephaly
      is a likely explanation for poorer post-surgery seizure control and cognitive
      outcomes. In addition, our findings support the hypothesis that HME pathogenesis
      probably involves somatic mutations that affect each developing cerebral
      hemisphere differently with more neurons than expected on the HME side.

PMID- 16291807
TI  - Memories for emotional autobiographical events following unilateral damage to
      medial temporal lobe.
AB  - Abnormalities of both memory and emotion have been reported in patients with
      unilateral damage to the anteromedial temporal lobe, probably reflecting the
      functions of the amygdala and hippocampus in these processes. Emotion and memory
      are also known to interact: emotional experiences often leave remarkably durable
      autobiographical memories. To explore this interaction, and to extend prior
      studies to the domain of autobiographical memory, we investigated the
      recollection of real-life emotional events in patients with unilateral damage to
      the anteromedial temporal lobe. Twenty-three patients who had undergone
      unilateral temporal lobectomy for the treatment of epilepsy (12 left, 11 right)
      and 20 healthy comparison participants completed an emotional autobiographical
      memory test. Participants were asked to recollect their five most emotional
      memories from any time in their lives and then they completed a word-cued
      autobiographical memory task. Participants dated each memory and gave ratings on
      scales of pleasantness, intensity, significance, novelty, vividness and frequency
      of rehearsal. Left temporal lobectomy (LTL) and healthy comparison groups
      generated similar numbers of pleasant and unpleasant memories, whereas the right
      temporal lobectomy (RTL) group produced significantly fewer memories of
      unpleasant events (P < 0.01). When memories were further categorized according to
      pleasantness and intensity, the RTL group produced significantly fewer
      unpleasant/high intensity memories than the other groups (P < 0.01). All groups
      reported more memories from between the ages of 10 and 30 (the so-called
      autobiographical memory 'bump'). The results demonstrate a positive bias in the
      recollection of autobiographical memory following right-sided anteromedial
      temporal damage. This finding is consistent with the notion that the right, but
      not the left, anteromedial temporal lobe is involved in the retrieval of
      negatively valenced, high-intensity memories.

PMID- 16291808
TI  - The epithelial Ca2+ channel TRPV5 is essential for proper osteoclastic bone
      resorption.
AB  - Bone remodeling involves the interplay of bone resorption and formation and is
      accurately controlled to maintain bone mass. Both processes require transcellular
      Ca(2+) transport, but the molecular mechanisms engaged remain largely elusive.
      The epithelial Ca(2+) channel TRPV5 is one of the most Ca(2+)-selective transient
      receptor potential (TRP) channels. In this study, the functional role of TRPV5 in
      bone was investigated. TRPV5 mRNA was expressed in human and murine bone samples
      and in osteoclasts along with other genes involved in transcellular Ca(2+)
      transport, including calbindin-D(9K) and calbindin-D(28K), Na(+)/Ca(2+) exchanger
      1, and plasma membrane Ca(2+)-ATPase 1b. TRPV5 expression in murine osteoclasts
      was confirmed by immunostaining and showed predominant localization to the
      ruffled border membrane. However, TRPV5 was absent in osteoblasts. Analyses of
      femoral bone sections from TRPV5 knockout (TRPV5(-/-)) mice revealed increased
      osteoclast numbers and osteoclast area, whereas the urinary bone resorption
      marker deoxypyridinoline was reduced compared with WT (TRPV5(+/+)) mice. In an in
      vitro bone marrow culture system, the amount of osteoclasts and number of nuclei
      per osteoclast were significantly elevated in TRPV5(-/-) compared with TRPV5(+/+)
      mice. However, using a functional resorption pit assay, we found that bone
      resorption was nearly absent in osteoclast cultures from TRPV5(-/-) mice,
      supporting the impaired resorption observed in vivo. In conclusion, TRPV5
      deficiency leads to an increase in osteoclast size and number, in which Ca(2+)
      resorption is nonfunctional. This report identifies TRPV5 as an epithelial Ca(2+)
      channel that is essential for osteoclastic bone resorption and demonstrates the
      significance of transcellular Ca(2+) transport in osteoclastic function.

PMID- 16291809
TI  - Diffusion-limited phase separation in eukaryotic chemotaxis.
AB  - The ability of cells to sense spatial gradients of chemoattractant factors
      governs the development of complex eukaryotic organisms. Cells exposed to shallow
      chemoattractant gradients respond with strong accumulation of the enzyme
      phosphatidylinositol 3-kinase (PI3K) and its D3-phosphoinositide product (PIP(3))
      on the plasma membrane side exposed to the highest chemoattractant concentration,
      whereas PIP(3)-degrading enzyme PTEN and its product PIP(2) localize in a
      complementary pattern. Such an early symmetry-breaking event is a mandatory step
      for directed cell movement elicited by chemoattractants, but its physical origin
      is still mysterious. Here, we propose that directional sensing is the consequence
      of a phase-ordering process mediated by phosphoinositide diffusion and driven by
      the distribution of chemotactic signal. By studying a realistic reaction
      diffusion lattice model that describes PI3K and PTEN enzymatic activity,
      recruitment to the plasma membrane, and diffusion of their phosphoinositide
      products, we show that the effective enzyme-enzyme interaction induced by
      catalysis and diffusion introduces an instability of the system toward phase
      separation for realistic values of physical parameters. In this framework, large
      reversible amplification of shallow chemotactic gradients, selective localization
      of chemical factors, macroscopic response timescales, and spontaneous
      polarization arise naturally. The model is robust with respect to order-of
      magnitude variations of the parameters.

PMID- 16291810
TI  - Transformation of breast cells by truncated neurokinin-1 receptor is secondary to
      activation by preprotachykinin-A peptides.
AB  - Breast cancer remains the cancer with the highest mortality among women in the
      United States. Peptides derived from the oncogenic Tac1 gene (full transcript:
      betaPPT-A) stimulate the proliferation of breast cancer cells (BCCs) via seven
      transmembrane G protein-coupled neurokinin 1 (NK1) and NK2 receptors. The NK1
      gene could generate full-length (NK1-FL) and truncated (NK1-Tr) transcripts. NK1
      Tr lacks 100 residues in their cytoplasmic end, could couple to G proteins, and
      shows reduced efficiency with respect to internalization and desensitization.
      This study reports on a role of NK1-Tr in the transformation of nontumorigenic
      breast cells, and investigates whether Tac1 expression is linked to the
      generation of NK1-Tr. Western blots and Northern analyses showed coexpressions of
      NK1-Tr and NK1-FL in BCCs (cell lines and primary cells from patients with
      different stages of breast cancer). Stable transfections of betaPPT-A or NK1-Tr
      expression vectors in nontumorigenic cells showed each induces the expression of
      the other, consequently resulting in a transformed phenotype. Analyses with
      microarrays indicate similar patterns of cytokine production by NK1-Tr
      transfectants and BCCs, but not NK1-FL transfectants. These observations indicate
      tumor-promoting properties by NK1-Tr, but not NK1-FL. Overall, the oncogenic
      property of Tac1 in breast cells involves concomitant expression of NK1-Tr and
      vice versa, consequently leading to the production of cytokines with growth
      promoting functions.

PMID- 16291811
TI  - Monetary value of lost productivity over a five year follow up in early
      rheumatoid arthritis estimated on the basis of official register data on
      patients' sickness absence and gross income: experience from the FIN-RACo trial.
AB  - OBJECTIVE: To explore the monetary value of rheumatoid arthritis related loss of
      productivity in patients with early active disease. METHODS: In a prospective
      cohort substudy of the FIN-RACo Trial, 162 patients with recent onset rheumatoid
      arthritis, aged 18 to 65 years and available to the workforce, were followed up
      for five years. Loss of work productivity in euros 2002 was estimated by data on
      absence for sickness and on income (human capital approach) from official
      databases. Treatment responses were evaluated by area under the curve (AUC) of
      the ACR-N measure and by increase in number of erosions in radiographs of hands
      and feet. The health assessment questionnaire (HAQ) at six months was linked to
      the International Classification of Functioning, Disability and Health (ICF).
      RESULTS: In all, 120 (75%) patients, women more often (82%) than men (61%)
      (p=0.002), lost work days. The mean lost productivity per patient-year was
      euro7217 (95% confidence interval (CI), 5561 to 9148): for women, euro6477 (4858
      to 8536) and for men, euro8443 (5389 to 12,898). There was an inverse correlation
      with improvement: euro1101 (323 to 2156) and euro14 952 (10,662 to 19,852) for
      the highest and lowest quartiles of AUC of ARC-N, respectively. Lost productivity
      was associated with increase in the number of erosions and with disability in
      "changing and maintaining body position" subcategory of the ICF. CONCLUSIONS:
      Despite remission targeted treatment with disease modifying antirheumatic drugs,
      early rheumatoid arthritis results in substantial loss of productivity. A good
      improvement in the disease reduces the loss markedly.

PMID- 16291812
TI  - B lymphocyte maturation in Wegener's granulomatosis: a comparative analysis of VH
      genes from endonasal lesions.
AB  - BACKGROUND: Anti-neutrophil cytoplasmic antibodies (ANCA) directed against
      proteinase 3 (PR3) are highly specific for Wegener's granulomatosis (WG).
      Evidence for a pivotal role of PR3-ANCA in the induction of vasculitis has been
      demonstrated. B cell clusters have been observed within endonasal biopsy
      specimens. OBJECTIVES: To determine whether B cell selection and maturation take
      place in granulomatous lesions of WG. METHODS: Granulomatous lesions and the
      immunoglobulin (VH) gene repertoire from nasal tissue of six WG patients-two
      active and two smouldering localised WG (ANCA negative, restricted to respiratory
      tract), plus one active and one smouldering PR3-ANCA positive generalised WG-were
      characterised by immunohistochemistry, polymerase chain reaction, cloning, DNA
      sequencing and database comparison. RESULTS: B lymphocyte-rich, follicle-like
      areas were observed proximal to PR3 positive cells and plasma cells in
      granulomatous lesions; 184 VH genes from these granulomatous lesions were
      compared with 84 VH genes from peripheral blood of a healthy donor. The
      mutational pattern of VH genes from active WG resembled memory B cells.
      Structural homologies of VH genes from granulomatous lesions to PR3-ANCA encoding
      genes were detected. Significantly more genes (55%, 45%, and 53%, respectively)
      from active WG compared with the healthy repertoire carried mutations to
      negatively charged amino acids within the binding site coding regions, favouring
      affinity to the positively charged PR3. CONCLUSIONS: Selection and affinity
      maturation of potentially PR3-ANCA producing autoreactive B cells may start in
      granulomatous lesions, thereby contributing to disease progression from ANCA
      negative localised to PR3-ANCA positive generalised WG.

PMID- 16291813
TI  - Most visits of most patients with rheumatoid arthritis to most rheumatologists do
      not include a formal quantitative joint count.
AB  - OBJECTIVE: To ask rheumatologists about the likelihood of performing a formal
      joint count at each visit of a patient with rheumatoid arthritis (RA) in standard
      clinical care. METHOD: Direct query of rheumatologists at an international
      meeting of about 600 rheumatologists from 17 European countries. RESULTS:
      Overall, 14% of rheumatologists reported performing a formal joint count at each
      visit of each patient, and 44% of rheumatologists reported performing a formal
      joint count at more than 50% of visits of patients with RA. Therefore, 56% of
      rheumatologists reported performing a joint count at fewer than 50% of visits,
      including 45% at fewer than 25% of visits. One in eight rheumatologists (13%)
      reported never performing a formal joint count. CONCLUSION: Although the joint
      count remains the most specific measure for RA, most visits of most patients with
      RA to most rheumatologists do not include a formal quantitative joint count.

PMID- 16291814
TI  - Gout, not induced by diuretics? A case-control study from primary care.
AB  - BACKGROUND: It is taken for granted that diuretics may induce gout, but there is
      a general lack of evidence on this topic. OBJECTIVES: To determine the incidence
      of gout in patients who use diuretics, taking into account concurrent
      hypertension and cardiovascular diseases. METHODS: A case-control study was
      designed. From a primary care population all patients with a first gout
      registration (59 men, 11 women; mean (SD) age 55.1 (13.5)) were identified as
      cases. To relate the occurrence of gout to diuretic use a matched reference
      series of three controls for each case was compiled. Conditional logistic
      regression analyses were applied to estimate incidence rate ratios (IRRs) of
      gout, and 95% confidence intervals (CIs), in subjects with and without diuretic
      treatment, hypertension, and cardiovascular diseases. Additional stratification
      analyses were made, particularly in the subjects not using diuretics. RESULTS:
      The IRRs of gout in subjects with v those without diuretic treatment,
      hypertension, heart failure, and myocardial infarction were 2.8 (95% CI 1.2 to
      6.6), 2.6 (95% CI 1.2 to 5.6), 20.9 (95% CI 2.5 to 173.8), and 1.9 (95% CI 0.7 to
      4.7), respectively. After adjustment, the IRR of gout for diuretic use dropped to
      0.6 (95% CI 0.2 to 2.0), while the IRRs of gout for hypertension, heart failure,
      and myocardial infarction were still >1. This was also the case for subjects with
      hypertension or myocardial infarction, who had not used diuretics. CONCLUSION:
      The results suggest that diuretics do not actually increase the risk of gout.
      Cardiovascular indications for treatment may have confounded previous inferences.

PMID- 16291815
TI  - P2X receptors in mouse Leydig cells.
AB  - ATP-activated currents were studied in Leydig cells of mice with the patch-clamp
      technique. Whole cell currents were rapidly activating and slowly desensitizing
      (55% decrement from the peak value on exposure to 100 microM ATP for 60 s),
      requiring 3 min of washout to recover 100% of the response. The concentration
      response relationships for ATP, adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS),
      and 2-methylthio-ATP (2-MeS-ATP) were described by the Hill equation with a
      concentration evoking 50% of maximal ATP response (K(d)) of 44, 110, and 637
      microM, respectively, and a Hill coefficient of 2. The order of efficacy of
      agonists was ATP >or= ATPgammaS > 2-MeS-ATP > 2',3'-O-(4-benzoylbenzoyl)-ATP
      (BzATP). alphabeta-Methylene-ATP (alphabeta-MeATP), GTP, UTP, cAMP, and adenosine
      were ineffective. Suramin and pyridoxal phosphate-6-azophenyl-2',4'-disulfonic
      acid (PPADS) blocked the responses in a concentration-dependent manner. The ATP
      activated currents were dependent on extracellular pH, being maximal at pH 6.5
      and decreasing with both acidification and alkalinization (apparent dissociation
      constant (pK(a)) of 5.9 and 7.4, respectively). The whole cell current-voltage
      relationship showed inward rectification and reversed near 0 mV. Experiments
      performed in bi-ionic conditions for measurement of reversal potentials showed
      that this channel is highly permeable to calcium [permeability (P)(Ca)/P(Na) =
      5.32], but not to chloride (P(Cl)/P(Na) = 0.03) or N-methyl-D-glucamine (NMDG)
      (P(NMDG)/P(Na) = 0.09). Unitary currents recorded in outside-out patches had a
      chord conductance of 27 pS (between -90 and -50 mV) and were inward rectifying.
      The average current passing through the excised patch decreased with time [time
      constant (tau) = 13 s], resembling desensitization of the macroscopic current.
      These findings indicate that the ATP receptor present in Leydig cells shows
      properties most similar to those of cloned homomeric P2X(2).

PMID- 16291816
TI  - Role of plasma membrane Ca2+-ATPase in contraction-relaxation processes of the
      bladder: evidence from PMCA gene-ablated mice.
AB  - We investigated the roles and relationships of plasma membrane Ca(2+)-ATPase
      (PMCA), sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)2, and Na(+)/Ca(2+)
      exchanger (NCX) in bladder smooth muscle contractility in Pmca-ablated mice:
      Pmca4-null mutant (Pmca4(-/-)) and heterozygous Pmca1 and homozygous Pmca4 double
      gene-targeted (Pmca1(+/-)Pmca4(-/-)) mice. Gene manipulation did not alter the
      amounts of PMCA1, SERCA2, and NCX. To study the role of each Ca(2+) transport
      system, contraction of circular ring preparations was elicited with KCl (80 mM)
      plus atropine, and then the muscle was relaxed with Ca(2+)-free physiological
      salt solution containing EGTA. We measured the contributions of Ca(2+) clearance
      components by inhibiting SERCA2 (with 10 microM cyclopiazonic acid) and/or NCX
      (by replacing NaCl with N-methyl-D-glucamine/HCl plus 10 microM KB-R7943).
      Contraction half-time (time to 50% of maximum tension) was prolonged in the gene
      targeted muscles but marginally shortened when SERCA2 or NCX was inhibited. The
      inhibition of NCX significantly inhibited this prolongation, suggesting that NCX
      activity might be augmented to compensate for PMCA4 function in the gene-targeted
      muscles under nonstimulated conditions. Inhibition of SERCA2 and NCX as well as
      gene targeting all prolonged the relaxation half-time. The contribution of PMCA
      to relaxation was calculated to be approximately 25-30%, with that of SERCA2
      being 20% and that of NCX being 70%. PMCA and SERCA2 appeared to function
      additively, but the function of NCX might overlap with those of other components.
      In summary, gene manipulation of PMCA indicates that PMCA, in addition to SERCA2
      and NCX, plays a significant role in both excitation-contraction coupling and the
      Ca(2+) extrusion-relaxation relationship, i.e., Ca(2+) homeostasis, of bladder
      smooth muscle.

PMID- 16291817
TI  - Effect of reduced oxygen tension on chondrogenesis and osteogenesis in adipose
      derived mesenchymal cells.
AB  - Recent studies have demonstrated that adipose-derived mesenchymal cells (AMCs)
      offer great promise for cell-based therapies because of their ability to
      differentiate toward bone, cartilage, and fat. Given that cartilage is an
      avascular tissue and that mesenchymal cells experience hypoxia during
      prechondrogenic condensation in endochondral ossification, the goal of this study
      was to understand the influence of oxygen tension on AMC differentiation into
      bone and cartilage. In vitro chondrogenesis was induced using a three-dimensional
      micromass culture model supplemented with TGF-beta1. Collagen II production and
      extracellular matrix proteoglycans were assessed with immunohistochemistry and
      Alcian blue staining, respectively. Strikingly, micromasses differentiated in
      reduced oxygen tension (2% O(2)) showed markedly decreased chondrogenesis.
      Osteogenesis was induced using osteogenic medium supplemented with retinoic acid
      or vitamin D and was assessed with alkaline phosphatase activity and
      mineralization. AMCs differentiated in both 21 and 2% O(2) environments. However,
      osteogenesis was severely diminished in a low-oxygen environment. These data
      demonstrated that hypoxia strongly inhibits in vitro chondrogenesis and
      osteogenesis in AMCs.

PMID- 16291818
TI  - Overexpression of inducible 70-kDa heat shock protein in mouse attenuates
      skeletal muscle damage induced by cryolesioning.
AB  - Heat shock protein expression is elevated upon exposure to a variety of stresses
      and limits the extent of stress-induced damage. To investigate the putative role
      of inducible 70-kDa heat shock protein (HSP70) in skeletal muscle damage and
      regeneration, soleus and tibialis anterior (TA) muscles from HSP70-overexpressing
      transgenic mice were subjected to cryolesioning and analyzed after 1, 10, and 21
      days. Histological analysis showed that the muscles from both HSP70 and wild-type
      mice treated with radicicol (a HSP inducer) had decreased necrosis after
      cryolesioning compared with controls. The decrease in muscle fiber cross
      sectional area in both soleus and TA muscles in 10 days postlesioning was
      attenuated in HSP70 mice compared with wild-type mice. Glutathione peroxidase
      activity was increased 1 day after cryolesioning in both HSP70 and control mice
      and remained elevated for up to 21 days. Immunodetection of neuronal cell
      adhesion molecule (a satellite cell marker) and developmental/neonatal MHC were
      significantly lower in cryolesioned HSP70-overexpressing mice than in
      cryolesioned controls. These results suggest that HSP70 protects skeletal muscle
      against injury and radicicol might be useful as a skeletal muscle protective
      agent.

PMID- 16291819
TI  - Inhibition of AIF-1 expression by constitutive siRNA expression reduces
      macrophage migration, proliferation, and signal transduction initiated by
      atherogenic stimuli.
AB  - Allograft inflammatory factor-1 (AIF-1) is a cytoplasmic, calcium-binding,
      inflammation-responsive scaffold protein. Several studies have reported increased
      AIF-1 expression in activated macrophages and have implicated AIF-1 as a marker
      of activated macrophages. However, the function of AIF-1 in macrophages and the
      mechanism whereby it participates in macrophage activation are unknown at this
      time. Immunohistochemical analysis colocalized AIF-1 expression with CD68
      positive macrophages in atherosclerotic human coronary arteries. Subsequent
      experiments were designed to determine a role for AIF-1 in macrophage activation
      in response to atherogenic stimuli. Stimulation of human and murine macrophages
      with oxidized LDL significantly increased AIF-1 expression above basal levels.
      Stable transfection of AIF-1 small interfering RNA (siRNA) in macrophages reduced
      AIF-1 protein expression by 79% and reduced macrophage proliferation by 52% (P <
      0.01). Inhibition of proliferation was not due to induction of apoptosis.
      Sequences that did not knock down AIF-1 expression had no effect on
      proliferation. AIF-1 siRNA expression reduced macrophage migration by 60% (P <
      0.01). Both proliferation and migration of siRNA-expressing macrophages could be
      restored by adenoviral expression of AIF-1 (P < 0.001 and 0.005, respectively),
      suggesting a tight association between AIF-1 expression and macrophage
      activation. Phosphorylation of Akt, p44/42 MAPK, and p38 kinase were
      significantly reduced in siRNA macrophages challenged with oxidized LDL (P <
      0.05). Phosphorylation of p38 kinase was significantly inhibited in siRNA
      macrophages stimulated with T lymphocyte conditioned medium (P < 0.05). These
      data indicate that AIF-1 mediates atherogenesis-initiated signaling and
      activation of macrophages.

PMID- 16291820
TI  - Heme oxygenase-1 mediates the anti-inflammatory actions of 2'-hydroxychalcone in
      RAW 264.7 murine macrophages.
AB  - Chalcones are a group of plant-derived polyphenolic compounds that belong to the
      flavonoids family, and possess a wide variety of cytoprotective and modulatory
      functions. Chalcones exert their cytoprotective actions via activation of
      specific transcriptional factors and upregulation of endogenous defensive
      pathways, such as phase II enzymes and the stress protein heme oxygenase-1 (HO
      1). In this study, we investigated the anti-inflammatory action of 2'
      hydroxychalcone (2-HC) in a model of lipopolysaccharide (LPS)-induced
      inflammation in RAW 264.7 macrophages and examined the role of HO-1 in this
      process. Our results demonstrate that 2-HC potently induces HO-1 expression and
      markedly reduces LPS-mediated nitrite and TNF-alpha production. These effects are
      accompanied by inhibition of inducible nitric oxide synthase protein expression
      and abolished by blockade of heme oxygenase activity with either tin
      protoporphyrin IX or HO-1 small interfering RNA. By using a pharmacological
      approach and siRNA technology, we also found that phosphatidylinositol 3-kinase
      is a major cellular mediator in 2-HC-induced HO-1 expression. These findings
      strongly suggest that 2-HC exerts anti-inflammatory actions via activation of the
      HO-1 pathway and help to elucidate the mechanisms underlying the potential
      therapeutic value of chalcones.

PMID- 16291821
TI  - Mechanical load-dependent regulation of satellite cell and fiber size in rat
      soleus muscle.
AB  - The effects of mechanical unloading and reloading on the properties of rat soleus
      muscle fibers were investigated in male Wistar Hannover rats. Satellite cells in
      the fibers of control rats were distributed evenly throughout the fiber length.
      After 16 days of hindlimb unloading, the number of satellite cells in the
      central, but not the proximal or distal, region of the fiber was decreased. The
      number of satellite cells in the central region gradually increased during the 16
      day period of reloading. The mean sarcomere length in the central region of the
      fibers was passively shortened during unloading due to the plantarflexed position
      at the ankle joint: sarcomere length was maintained at <2.1 microm, which is a
      critical length for tension development. Myonuclear number and domain size, fiber
      cross-sectional area, and the total number of mitotically active and quiescent
      satellite cells of whole muscle fibers were lower than control fibers after 16
      days of unloading. These values then returned to control values after 16 days of
      reloading. These results suggest that satellite cells play an important role in
      the regulation of muscle fiber properties. The data also indicate that the
      satellite cell-related regulation of muscle fiber properties is dependent on the
      level of mechanical loading, which, in turn, is influenced by the mean sarcomere
      length. However, it is still unclear why the region-specific responses, which
      were obvious in satellite cells, were not induced in myonuclear number and fiber
      cross-sectional area.

PMID- 16291822
TI  - Estradiol-17beta stimulates proliferation of mouse embryonic stem cells:
      involvement of MAPKs and CDKs as well as protooncogenes.
AB  - Although the importance of estradiol-17beta (E(2)) in many physiological
      processes has been reported, to date no researchers have investigated the effects
      of E(2) on embryonic stem (ES) cell proliferation. Therefore, in the present
      study, we have examined the effect of E(2) on the DNA synthesis of murine ES (ES
      E14TG2a) cells and its related signaling pathways. The results of this study show
      that E(2) (10(-9) M) significantly increased [(3)H]thymidine incorporation at >4
      h and that E(2) (>10(-12) M) induced an increase of [(3)H]thymidine incorporation
      after 8-h incubation. Moreover, E(2) (>10(-12) M) also increased 5'-bromo-2'
      deoxyuridine (BrdU) incorporation and cell number. Indeed, E(2) stimulated
      estrogen receptor (ER)-alpha and -beta protein levels and increased mRNA
      expression levels of protooncogenes (c-fos, c-jun, and c-myc). Tamoxifen
      (antiestrogen) completely inhibited E(2)-induced increases in [(3)H]thymidine
      incorporation. In addition, estradiol-6-O-carboxymethyl oxime-BSA (E(2)-BSA; 10(
      9) M) increased [(3)H]thymidine incorporation at >1 h, and E(2)-BSA (>10(-12) M)
      increased [(3)H]thymidine incorporation after 1-h incubation. E(2)-BSA-induced
      increase in BrdU incorporation also occurred in a dose-dependent manner.
      Tamoxifen had no effect on E(2)-BSA-induced increase of [(3)H]thymidine
      incorporation. Also, E(2) and E(2)-BSA displayed maximal phosphorylation of
      p44/42 MAPKs at 10 and 5 min, respectively. E(2) increased cyclins D1 and E as
      well as cyclin-dependent kinase (CDK)2 and CDK4. In contrast, E(2) decreased the
      levels of p21(cip1) and p27(kip1) (CDK-inhibitory proteins). Increases of these
      cell cycle regulators were blocked by 10(-5) M PD-98059 (MEK inhibitor).
      Moreover, E(2)-induced increase of [(3)H]thymidine incorporation was inhibited by
      PD-98059 or butyrolactone I (CDK2 inhibitor). In conclusion, estradiol-17beta
      stimulates the proliferation of murine ES cells, and this action is mediated by
      MAPKs, CDKs, or protooncogenes.

PMID- 16291823
TI  - Commentary: benchmarks for work performance of pediatric psychologists.

PMID- 16291824
TI  - Genetic differences in lethality of newborn mice treated in utero with coplanar
      versus non-coplanar hexabromobiphenyl.
AB  - Polybrominated biphenyl (PBB) exposure in humans is known to cause immunotoxicity
      and disorders related to the central nervous system. Coplanar PBBs bind to the
      aryl hydrocarbon receptor (AHR) in vertebrates. We compared the coplanar PBB,
      3,3',4,4',5,5'-hexabromobiphenyl (cHBB), with its stereoisomer, the non-coplanar
      PBB, 2,2',4,4'6,6'-hexabromobiphenyl (ncHBB), using C57BL/6J (B6) inbred mice
      (having the high-affinity AHR) and congenic B6.D2-Ahr d mice (having the low
      affinity AHR in a >99.8% C57BL/6J genetic background). Pregnant dams were treated
      i.p. with vehicle alone, cHBB, or ncHBB on gestational day 5 (GD 5).
      Unexpectedly, neonatal lethality within the first 72 h postpartum was significant
      in cHBB-treated B6 mice at doses as low as 2.5 mg/kg, whereas no deaths were seen
      in B6 pups whose mother had received ncHBB 100 mg/kg or in either B6.D2-Ahr d or
      Ahr(-/-) knockout mice whose mother had received cHBB 100 mg/kg. Histological and
      gross anatomical analyses of a battery of tissues in the mother or fetus at GD
      18, as well as 24 h postpartum, revealed no significant differences, except for
      decreased thymus and spleen weights in cHBB-treated B6 GD 18 fetuses. Cross
      fostering and genetics experiments confirmed the association of neonatal deaths
      principally with in utero (rather than lactational) exposure to cHBB, and also no
      paternal effect. For the end points of mouse neonatal lethality and
      immunotoxicity, cHBB appears to act through the high-affinity AHR receptor.
      Although dioxin in utero is well known to cause AHR-dependent cleft palate and
      hydronephrosis, cHBB did not; thus, chronic activation of the AHR appears to be
      necessary but not sufficient for AHR-mediated teratogenicity.

PMID- 16291825
TI  - Dietary copper enhances the peripheral myelinopathy produced by oral pyrrolidine
      dithiocarbamate.
AB  - The neurotoxic hazard of a dithiocarbamate is influenced by route of exposure and
      acid stability of the dithiocarbamate. As an example, oral administration of the
      acid labile dithiocarbamate N,N-diethyldithiocarbamate (DEDC) causes a central
      peripheral axonopathy thought to result from acid-promoted decomposition to CS2
      in the stomach. In contrast, parenteral administration of DEDC, which bypasses
      the acidic environment of the stomach, causes a primary demyelination that is
      thought to be mediated through the intact parent dithiocarbamate. The relative
      acid stability of pyrrolidine dithiocarbamate (PDTC) suggests that a significant
      portion of a dose can be absorbed intact following oral exposure with the
      potential to produce a primary myelin injury. The present study was performed to
      characterize the neurotoxicity of PDTC and evaluate the possible role of copper
      in dithiocarbamate-mediated demyelination. Male Sprague Dawley rats were
      administered PDTC in drinking water and given either a normal- or high-copper
      diet for 18, 47, or 58 weeks. Examination of peripheral nerve by light microscopy
      and electron microscopy at the end of exposures revealed primary myelin lesions
      and axonal degeneration in the PDTC groups, with a significant increase in the
      severity of several lesions observed for the PDTC, high-copper group relative to
      the PDTC normal-copper diet. ICP-AES metal analysis determined that the PDTC
      groups had significantly increased brain copper, and at 58 weeks a significant
      increase in copper was seen in the sciatic nerve of PDTC high-copper animals
      relative to PDTC normal-copper diet animals. Although RP-HPLC analysis could not
      detect globin alkylaminocarbonyl cysteine modifications analogous to those seen
      with parenteral DEDC, LC/MS/MS identified (pyrrolidin-1-yl carbonyl)cysteine
      adducts on PDTC-exposed rat globin. These findings are consistent with previous
      studies supporting the ability of acid-stable dithiocarbamates to mediate myelin
      injury following oral exposure. The greater severity of lesions associated with
      dietary copper supplementation and elevated copper levels in nerve also suggests
      that perturbation of copper homeostasis may contribute to the development of
      myelin lesions.

PMID- 16291826
TI  - Apoptosis induced by atRA in MEPM cells is mediated through activation of caspase
      and RAR.
AB  - We have previously demonstrated that all-trans retinoic (atRA) induced growth
      inhibition and apoptosis in mouse embryonic palate mesenchymal cells (MEPM). In
      the present study, we investigated the molecular mechanisms of atRA-induced
      apoptosis and its putative action pathway. atRA-induced apoptosis is associated
      with activation of the initiator caspase-9 and the effector caspase-3, but not of
      the effector caspase-8. A broad caspase inhibitor (z-VAD-fmk), caspase-9
      inhibitor z-LEHD-fmk and caspase-3 inhibitor (z-DEVD-fmk) blocked atRA-induced
      DNA fragmentation and sub-G1 fraction, but not caspase-8 inhibitor z-IETD-fmk. We
      further showed that atRA dose-dependently promoted mRNA expression of retinoic
      acid receptor beta (RAR-beta) and gamma. A weaker increase in RAR-alpha mRNA was
      seen only at the highest concentration of atRA (5 muM). The pan RAR antagonist,
      BMS493, completely abrogated atRA-induced DNA fragmentation, Sub-G1 fraction, and
      caspase-3 activation. Taken together, these findings show that caspase-mediated
      induction of apoptosis by atRA is an RAR-dependent signaling pathway.

PMID- 16291827
TI  - Developmental expression of aldehyde dehydrogenase in rat: a comparison of liver
      and lung development.
AB  - Metabolism is one of the major determinants for age-related changes in
      susceptibility to chemicals. Aldehydes are highly reactive molecules present in
      the environment that also can be produced during biotransformation of xenobiotics
      and endogenous metabolism. Although the lung is a major target for aldehyde
      toxicity, early development of aldehyde dehydrogenases (ALDHs) in lung has been
      poorly studied. The expression of ALDH in liver and lung across ages (postnatal
      day 1, 8, 22, and 60) was investigated in Wistar-Han rats. In adult, the majority
      of hepatic ALDH activity was found in mitochondria, while cytosolic ALDH activity
      was the highest contributor in lung. Total aldehyde oxidation capability in liver
      increases with age, but stays constant in lung. These overall developmental
      profiles of ALDH expression in a tissue appear to be determined by the different
      composition of ALDH isoforms within the tissue and their independent temporal and
      tissue-specific development. ALDH2 showed the most notable tissue-specific
      development. Hepatic ALDH2 was increased with age, while the pulmonary form did
      not. ALDH1 was at its maximum value at postnatal day 1 (PND1) and decreased
      thereafter both in liver and lung. ALDH3 increased with age in liver and lung,
      although ALDH3A1 was only detectible in lung. Collectively, the present study
      indicates that, in the case of aldehyde exposure, the in vivo responses would be
      tissue and age dependent.

PMID- 16291828
TI  - AhR-agonist-induced transcriptional changes of genes involved in thyroid function
      in primary porcine thyrocytes.
AB  - The Ah receptor (AhR) is a ligand transcription factor mediating toxic effects of
      chemicals such as dioxins. The 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) and the
      coplanar polychlorinated biphenyl 126 (PCB 126) are member of the polyhalogenated
      aromatic hydrocarbons family exerting a variety of toxic effects in a tissue
      specific and species-specific manner including thyroid function. In the present
      study, we aimed to investigate the effects of TCDD (1 and 10 nM) and dioxin-like
      PCB 126 (306 nM) on the AhR signaling pathway and on the gene expression profiles
      of key factors involved in thyroid function, including thyroglobulin (TG),
      thyroid peroxidase (TPO), the sodium iodide symporter (NIS), TSH receptor (TSHR),
      and cathepsins (Cat B and L), using a primary porcine thyrocyte culture as the
      experimental model. AhR and ARNT expression was detected both as mRNA and on the
      protein level. Expression did not vary upon treatment with either TCDD or PCB
      126. However, treatment with TCDD and PCB 126 induced an AhR signaling response,
      as indicated by the expression of the AhR-target gene cytochrome P-450 1A1
      (CYP1A1). Both 10 nM TCDD and PCB 126 treatment induced a significant
      downregulation in the expression of NIS and cathepsin B without affecting any of
      the other parameters investigated. In conclusion, these data indicate that (a)
      thyrocytes are targets of TCDD and TCDD-like compounds and (b) there is evidence
      for two independent most likely AhR-mediated molecular mechanisms, by which these
      compounds negatively interfere with thyroid function.

PMID- 16291829
TI  - Pulmonary Sporothrix schenckii infection in a HIV positive child.
AB  - Sporothrix schenckii is a ubiquitous fungus, causing mostly non life-threatening
      localized infections of the skin and subcutaneous tissues that can be treated
      with oral antifungal agents. Meningeal, pulmonary and osteoarticular
      dissemination occur mainly in immunosuppressed patients. Pulmonary sporotrichosis
      is rare and responds poorly to treatment. Cases of disseminated sporotrichosis
      have most frequently been reported in patients residing in South America and
      Asia, and have increasingly been reported in AIDS patients. The distribution and
      pathogenicity of S. schenckii in Sub-Saharan Africa is not well known. We report
      a case of invasive pulmonary sporotrichosis in an eleven year old HIV-infected
      boy in Kinshasa, Democratic Republic of the Congo, successfully treated with oral
      fluconazole.

PMID- 16291830
TI  - Vitamin E and vitamin C supplementation does not improve the clinical course of
      measles with pneumonia in children: a controlled trial.

PMID- 16291831
TI  - The relationship between behavioral states and pain responses to various NICU
      procedures in premature infants.
AB  - An explanatory observational study was conducted to assess the behavioral state
      before and during various procedures in the neonatal intensive care unit (NICU)
      and to investigate the relationship between the behavioral state measured by
      Anderson Behavioral State Scoring System (ABSS) and the degree of pain responses
      as measured using CRIES (Crying, Requires O(2) for oxygen saturation above 95,
      Increased vital signs, Expression, and Sleeplessness.) and PIPP (Premature
      Infants' Pain Profile). Ninety-one observations in 6 NICU procedures were made
      from 54 infants with a mean gestational age (GA) of 30(+4) weeks and a mean body
      weight (BW) of 1484.87 g. A positive relationship was identified between ABSS and
      CRIES, both before (r=0.244, p=0.020) and during (r=0.745, p=0.000) the
      procedures, and between CRIES and PIPP (r=0.447, p=0.000) during the procedures.
      However, no correlation was identified between PIPP and ABSS before (r=-0.055,
      p=0.651) and during (r=0.214, p=0.074) the procedures. This study concluded that
      relatively healthy, premature infants are in a state of quiet or active sleep and
      can adequately express pain-related responses to the NICU procedures that are
      appropriate with the nature of stimulation. However, it was observed that
      clinicians tend to pay little attention to the state of premature infants before
      performing the procedures, regardless of their invasive and stimulatory nature.
      Further research needs to be conducted on the pain responses in physiologic and
      behavioral expression of critically ill infants who possibly have alteration and
      developmental limitations in response.

PMID- 16291832
TI  - Magnitude and features of scrub typhus and spotted fever in children in India.

PMID- 16291833
TI  - Mass needle stick injury in children from the Western cape.
AB  - Illegal dumping of contaminated medical waste occurs commonly in South Africa.
      There is little information on the management and outcome of the children exposed
      to and injured by medical waste. On 15 September 1999, 54 children where involved
      in a mass exposure incident. 44 presented the same evening and 10 following day.
      Used needles and syringes were discarded on their soccer field. Children gave one
      another injections and played darts with the discarded needles. Parents were
      counselled and blood was drawn for HIV and Hepatitis B virus (HBV) serology. All
      were given HBV vaccination (HBVV). Stat doses of zidovudine (ZDV) and lamivudine
      (LMV) were given to all with visible wounds or history of percutaneous injury.
      Younger children were given prophylaxis as we considered their histories
      unreliable. Further visits were conducted at the community clinic for patient
      convenience. Children were reviewed at weeks 1 and 3 for drug adherence and side
      effects. At week 4, the second HBVV was given. At 3 months and 6 months HIV and
      HBV serology were repeated. 18/44 (40 per cent) had entry wounds. 44/54 (81 per
      cent) were given antiretroviral treatment (ART). Initial screening for HIV was
      negative in all, 6 had antibodies to HBV surface antigen, and 2 were HBV surface
      antigen positive. At week 1 all patients on ART were seen but at week 3 only 30
      (55 per cent) attended. 41 (75 per cent) attended at 4 weeks, 8 non-attendees
      being located by primary healthcare workers. At 3 months, none of the 35 (64 per
      cent) children had seroconverted for either virus. 44 (81 per cent) attended at 6
      months and all serology was negative. All were also Hepatitis C negative. The
      exposure incident sensitized the community to HIV. Follow up of patients after
      mass exposure is difficult and time-consuming. Adherence to ART was poor and
      should be carefully monitored. ZDV was probably adequate for this incident. In a
      non-mobile community a 3 month visit unnecessary.

PMID- 16291835
TI  - Identification of novel protein targets for modification by 15-deoxy-Delta12,14
      prostaglandin J2 in mesangial cells reveals multiple interactions with the
      cytoskeleton.
AB  - The cyclopentenone prostaglandin 15-deoxy-Delta12,14-PGJ2 (15d-PGJ2) has been
      shown to display protective effects against renal injury or inflammation. In
      cultured mesangial cells (MC), 15d-PGJ2 inhibits the expression of
      proinflammatory genes and modulates cell proliferation. Therefore, cyclopentenone
      prostaglandins (cyPG) have been envisaged as a promise in the treatment of renal
      disease. The effects of 15d-PGJ2 may be dependent on or independent from its role
      as a peroxisome proliferator-activated receptor agonist. It was shown recently
      that an important determinant for the peroxisome proliferator-activated receptor
      independent effects of 15d-PGJ2 is the capacity to modify proteins covalently and
      alter their function. However, a limited number of protein targets have been
      identified to date. Herein is shown that a biotinylated derivative of 15d-PGJ2
      recapitulates the effects of 15d-PGJ2 on the stress response and inhibition of
      inducible nitric oxide synthase levels and forms stable adducts with proteins in
      intact MC. Biotinylated 15d-PGJ2 was then used to identify proteins that
      potentially are involved in cyPG biologic effects. Extracts from biotinylated 15d
      PGJ2-treated MC were separated by two-dimensional electrophoresis, and the spots
      of interest were analyzed by mass spectrometry. Identified targets include
      proteins that are regulated by oxidative stress, such as heat-shock protein 90
      and nucleoside diphosphate kinase, as well as proteins that are involved in
      cytoskeletal organization, such as actin, tubulin, vimentin, and tropomyosin.
      Biotinylated 15d-PGJ2 binding to several targets was confirmed by avidin pull
      down. Consistent with these findings, 15d-PGJ2 induced early reorganization of
      vimentin and tubulin in MC. The cyclopentenone moiety and the presence of
      cysteine were important for vimentin rearrangement. These studies may contribute
      to the understanding of the mechanism of action and therapeutic potential of
      cyPG.

PMID- 16291834
TI  - hepatocyte growth factor is a downstream effector that mediates the antifibrotic
      action of peroxisome proliferator-activated receptor-gamma agonists.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand
      dependent transcription factor that plays an important role in the regulation of
      insulin sensitivity and lipid metabolism. Evidence shows that PPAR-gamma agonists
      also ameliorate renal fibrotic lesions in both diabetic nephropathy and
      nondiabetic chronic kidney disease. However, little is known about the mechanism
      underlying their antifibrotic action. This study demonstrated that PPAR-gamma
      agonists could exert their actions by inducing antifibrotic hepatocyte growth
      factor (HGF) expression. Incubation of mesangial cells with natural or synthetic
      PPAR-gamma agonists 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) or
      troglitazone and ciglitazone suppressed TGF-beta1-mediated alpha-smooth muscle
      actin, fibronectin, and plasminogen activator inhibitor-1 expression. PPAR-gamma
      agonists also induced HGF mRNA expression and protein secretion. Transfection
      studies revealed that 15d-PGJ2 stimulated HGF gene promoter activity, which was
      dependent on the presence of a novel peroxisome proliferator response element.
      Treatment of mesangial cells with 15d-PGJ2 induced the binding of PPAR-gamma to
      the peroxisome proliferator response element in the HGF promoter region. PPAR
      gamma agonists also activated c-met receptor tyrosine phosphorylation, induced
      Smad transcriptional co-repressor TG-interacting factor expression, and blocked
      TGF-beta/Smad-mediated gene transcription in mesangial cells. Furthermore,
      ablation of c-met receptor through the LoxP-Cre system in mesangial cells
      abolished the antifibrotic effect of 15d-PGJ2. PPAR-gamma activation also induced
      HGF expression in renal interstitial fibroblasts and repressed TGF-beta1-mediated
      myofibroblast activation. Both HGF and 15d-PGJ2 attenuated Smad nuclear
      translocation in response to TGF-beta1 stimulation in renal fibroblasts.
      Together, these findings suggest that HGF may act as a downstream effector that
      mediates the antifibrotic action of PPAR-gamma agonists.

PMID- 16291836
TI  - Inducible co-stimulator null MRL-Faslpr mice: uncoupling of autoantibodies and T
      cell responses in lupus.
AB  - MRL/MpJ-Tnfrsf6lpr (MRL-Faslpr) mice develop a spontaneous T cell-dependent
      autoimmune disease that shares features with human lupus, including fatal
      nephritis, systemic pathology, and autoantibodies (autoAb). The inducible co
      stimulator (ICOS) is upregulated on activated T cells and modulates T cell
      mediated responses. To investigate whether ICOS has an essential role in
      regulating autoimmune lupus nephritis and the systemic illness in MRL-Faslpr
      mice, ICOS null (-/-) MRL Faslpr and ICOS intact (+/+) MRL-Faslpr strains (wild
      type [WT]) were generated and compared. It was determined that in ICOS-/- MRL
      Faslpr as compared with the WT strain, (1) there is a significant reduction in
      circulating IgG and double-stranded DNA autoantibody isotype titers, and (2)
      there is an amplification of the frequency of intrarenal T cells generating IFN
      gamma and TNF-alpha in ICOS-/- versus WT mice. Of note, eliminating ICOS in the
      MRL-Faslpr strain does not alter renal pathology or function. Despite the
      reduction in circulating IgG and autoantibody isotypes (G1, G2a, and G2b), the
      amount of these IgG isotypes depositing in kidneys is similar. Furthermore, the
      systemic illness (skin, salivary and lacrimal glands, lungs, lymphadenopathy, and
      splenomegaly) is equivalent in ICOS-/- MRL-Faslpr and WT mice. These findings
      highlight the danger of relying on individual parameters, such as quantitative
      serum Ig levels and T cell functions, as prognostic indicators of lupus.

PMID- 16291837
TI  - Chronic hypoxia and tubulointerstitial injury: a final common pathway to end
      stage renal failure.
AB  - Recent studies emphasize the role of chronic hypoxia in the tubulointerstitium as
      a final common pathway to end-stage renal failure. When advanced,
      tubulointerstitial damage is associated with the loss of peritubular capillaries.
      Associated interstitial fibrosis impairs oxygen diffusion and supply to tubular
      and interstitial cells. Hypoxia of tubular cells leads to apoptosis or epithelial
      mesenchymal transdifferentiation. This in turn exacerbates fibrosis of the kidney
      and subsequent chronic hypoxia, setting in train a vicious cycle whose end point
      is ESRD. A number of mechanisms that induce tubulointerstitial hypoxia at an
      early stage have been identified. Glomerular injury and vasoconstriction of
      efferent arterioles as a result of imbalances in vasoactive substances decrease
      postglomerular peritubular capillary blood flow. Angiotensin II not only
      constricts efferent arterioles but, via its induction of oxidative stress, also
      hampers the efficient utilization of oxygen in tubular cells. Relative hypoxia in
      the kidney also results from increased metabolic demand in tubular cells.
      Furthermore, renal anemia hinders oxygen delivery. These factors can affect the
      kidney before the appearance of significant pathologic changes in the vasculature
      and predispose the kidney to tubulointerstitial injury. Therapeutic approaches
      that target the chronic hypoxia should prove effective against a broad range of
      renal diseases. Current modalities include the improvement of anemia with
      erythropoietin, the preservation of peritubular capillary blood flow by blockade
      of the renin-angiotensin system, and the use of antioxidants. Recent studies have
      elucidated the mechanism of hypoxia-induced transcription, namely that prolyl
      hydroxylase regulates hypoxia-inducible factor. This has given hope for the
      development of novel therapeutic approaches against this final common pathway.

PMID- 16291839
TI  - The heart of children with steroid-resistant nephrotic syndrome: is it all
      podocin?
AB  - Mutations in the gene NPHS2 encoding podocin are responsible for a recessive form
      of steroid-resistant nephrotic syndrome (SRNS). The common phenotype is of
      massive proteinuria in early childhood that tends to progress to end-stage renal
      failure. Extrarenal manifestations have not been described. Twenty-two children
      with SRNS from six unrelated Arab families were found to be homozygous for the
      R138X mutation in NPHS2. Eighteen patients underwent cardiac evaluation at
      diagnosis of SRNS while they had normal BP and preserved renal function. Cardiac
      anomalies were detected in 16 (89%) children: Left ventricular hypertrophy in
      eight, pulmonary stenosis in six, discrete subaortic stenosis in two, and Ebstein
      anomaly and ventricular septal defect in one each. The remaining four affected
      individuals were assessed only once they had end-stage renal failure. They had
      severe left ventricular hypertrophy and experienced repeated episodes of heart
      failure. Two control groups were equally evaluated. The first consisted of 37
      siblings without nephrotic syndrome, of whom only one carrier had a cardiac
      defect (P < 0.001). None of the second group, which included 22 children with
      persistent nephrotic syndrome as a result of other causes, had a cardiac anomaly
      (P < 0.001). Cardiac disorders in homozygotes for mutations in NPHS2 cannot be
      attributed to an association by chance or to a state of persistent nephrotic
      syndrome. Because human podocin mRNA is expressed in fetal heart, it is
      speculated that it may have a role in normal cardiac development. Cardiac
      evaluation is recommended at the time of diagnosis of SRNS due to mutations in
      podocin.

PMID- 16291838
TI  - Increased parathyroid hormone gene expression in secondary hyperparathyroidism of
      experimental uremia is reversed by calcimimetics: correlation with
      posttranslational modification of the trans acting factor AUF1.
AB  - Most patients with chronic kidney disease develop secondary hyperparathyroidism
      with disabling systemic complications. Calcimimetic agents are effective tools in
      the management of secondary hyperparathyroidism, acting through allosteric
      modification of the calcium-sensing receptor (CaR) on the parathyroid gland (PT)
      to decrease parathyroid hormone (PTH) secretion and PT cell proliferation. This
      study showed that rats that were fed an adenine high-phosphorus diet had
      increased serum PTH and PTH mRNA levels at 7 and 21 d. For studying the effect of
      activation of the CaR by the calcimimetics R-568 on PTH gene expression, R-568
      was given by gavage to uremic rats for the last 4 d of a 7-d adenine high
      phosphorus diet. R-568 decreased both PTH mRNA and serum PTH levels. The effect
      of the calcimimetic on PTH gene expression was posttranscriptional and correlated
      with differences in protein-RNA binding and posttranslational modifications of
      the trans acting factor AUF1 in the PT. The AUF1 modifications as a result of
      uremia were reversed by treatment with R-568 to those of normal rats. Therefore,
      uremia and activation of the CaR mediated by calcimimetics modify AUF1
      posttranslationally. These modifications in AUF1 correlate with changes in
      protein-PTH mRNA binding and PTH mRNA levels.

PMID- 16291840
TI  - Kidney function and mortality among patients with left ventricular systolic
      dysfunction.
AB  - Kidney disease has emerged as a risk factor for mortality in heart failure
      populations. The objective of this study was to determine the impact of different
      stages of kidney dysfunction (defined using the Kidney Disease Outcomes Quality
      Initiative [K/DOQI] classification system) and changes in kidney function on
      mortality in a cohort of patients with heart failure. A retrospective analysis
      was conducted of data from the randomized controlled trials Studies of Left
      Ventricular Dysfunction. A total of 6640 participants with asymptomatic and
      symptomatic heart failure were studied. Estimated GFR (eGFR) were calculated and
      then categorized according to the K/DOQI classification system into the following
      categories: > or =90, 60 to 89, 30 to 59, and 15 to 29 ml/min per 1.73 m2.
      Reduction in eGFR from baseline was calculated and subsequently categorized
      according to rate of decline (<5, 5 to 10, 11 to 15, and >15 ml/min per 1.73 m2
      per year). Independent of baseline differences, lower levels of eGFR were
      associated with a higher total mortality compared with those with eGFR > or =90
      ml/min (30 to 59 ml/min per 1.73 m2: hazard ratio [HR] 1.32, 95% confidence
      interval [CI] 1.10 to 1.59, P = 0.004; 15 to 29 ml/min per 1.73 m2: HR 2.54, 95%
      CI 1.54 to 4.19, P < 0.001). eGFR deteriorated rapidly (>15 ml/min per 1.73 m2
      per year) in 12% of participants. This decline was associated with a significant
      increase in mortality compared with slower decline (<5 ml/min per 1.73 m2 per
      year), despite adjustments for baseline kidney function, baseline heart failure,
      or change in heart failure (HR 5.63; 95% CI 4.90 to 6.46; P < 0.0001). The levels
      of eGFR from the K/DOQI classification system are associated with mortality in a
      well-characterized heart failure population. Rate of decline in kidney function
      is a strong predictor of increased mortality in this population, independent of
      worsening heart failure and baseline kidney function.

PMID- 16291841
TI  - Tissue-type plasminogen activator modulates inflammatory responses and renal
      function in ischemia reperfusion injury.
AB  - Acute renal failure is often the result of ischemia-reperfusion (I/R) injury.
      Neutrophil influx is an important damaging event in I/R. Tissue-type plasminogen
      activator (tPA) not only is a major fibrinolytic agent but also is involved in
      inflammatory processes. A distinct upregulation of tPA after I/R, with de novo
      tPA production by proximal renal tubules, was found. For investigating the role
      of tPA in I/R, renal ischemia was induced in tPA-/- and wild-type (WT) mice by
      clamping both renal arteries for 35 min followed by reperfusion. Mice were killed
      1, 5, and 10 d after reperfusion. After 1 d, tPA-/- mice displayed significantly
      less neutrophil influx into the interstitial area compared with WT mice. In
      addition, tPA-/- mice showed quicker recovery of renal function than WT mice. The
      protocol was repeated after injection of tPA-antisense oligonucleotides into WT
      mice, leading to even more explicit results: Antisense-treated mice showed less
      histologic damage, better renal function, and less neutrophil influx than control
      mice. Surprising, complement C3 concentration, levels of proinflammatory
      cytokines and chemokines, intercellular adhesion molecule-1 expression, and
      matrix metalloproteinase activity were similar in WT and tPA-/- mice. Plasmin
      activity levels in WT and tPA-/- kidneys were also comparable, indicating that
      tPA influences neutrophil influx into ischemic renal tissue independent from
      plasmin generation. This study shows that targeting tPA could be of therapeutic
      importance in treating I/R injury by diminishing neutrophil influx and preserving
      renal function.

PMID- 16291842
TI  - Effectiveness of extracorporeal shockwave treatment in 353 patients with chronic
      plantar fasciitis.
AB  - A 16-question post-treatment survey was sent to 874 patients after extracorporeal
      shockwave treatment for chronic plantar fasciitis. Of the 377 surveys returned,
      353 were used for analysis. These patients were treated by 169 physicians in 19
      states using either electrohydraulic or electromagnetic extracorporeal shockwave
      equipment. Seventy-six percent of the patients underwent treatment after having
      had continued pain for a year or longer. Seventy percent of patients who rated
      their pretreatment pain level as severe (score >or= 8 on a scale from 1 to 10)
      experienced sharp declines in pain, with a sharp decline considered to be a
      difference in pain level before and after treatment of 3 or more. In addition,
      66% of patients who rated their pretreatment immobility as severe (score >or= 8
      on a scale from 1 to 10) experienced sharp declines in immobility. Of the
      patients who underwent extracorporeal shockwave treatment, 69% indicated that
      they would recommend this procedure to someone in a similar situation. If
      extracorporeal shockwave treatment were not available, 62% of patients indicated
      that they would have undergone open or invasive surgery, and 41% indicated that
      they would have continued with additional physician office visits.

PMID- 16291843
TI  - Effectiveness of low-Dye taping for the short-term management of plantar
      fasciitis.
AB  - Low-Dye taping is often used as a short-term treatment for plantar fasciitis. We
      evaluated the short-term effectiveness of low-Dye taping in relieving pain
      associated with plantar fasciitis. In this comparative study conducted at a
      university-based clinic, 65 participants with plantar fasciitis who received low
      Dye taping for 3 to 5 days were compared with 40 participants who did not receive
      taping. Pain before and after treatment was measured using a visual analog pain
      scale. Analysis of the data was by the intention-to-treat principle, and a linear
      regression approach to analysis of covariance was used to compare effects. The
      visual analog pain scale score improved by a mean of 20 mm (from 44 to 24 mm) in
      the taping group and worsened by a mean of 6 mm (from 51 to 57 mm) in the control
      group. The analysis of covariance-adjusted difference in therapeutic effect
      favored the taping group by 31.7 mm (95% confidence interval, 23.6-39.9 mm) and
      was statistically significant (t = 7.71). In the short term, low-Dye taping
      significantly reduces the pain associated with plantar fasciitis. These findings
      are the first quantitative results to demonstrate the significant therapeutic
      effect of this treatment modality in relieving the symptoms associated with
      plantar fasciitis.

PMID- 16291844
TI  - Effects of simulated genu valgum and genu varum on ground reaction forces and
      subtalar joint function during gait.
AB  - The mechanical effects of genu valgum and varum deformities on the subtalar joint
      were investigated. First, a theoretical model of the forces within the foot and
      lower extremity during relaxed bipedal stance was developed predicting the
      rotational effect on the subtalar joint due to genu valgum and varum deformities.
      Second, a kinetic gait study was performed involving 15 subjects who walked with
      simulated genu valgum and genu varum over a force plate and a plantar pressure
      mat to determine the changes in the ground reaction force vector within the
      frontal plane and the changes in the center-of-pressure location on the plantar
      foot. These results predicted that a genu varum deformity would tend to cause a
      subtalar pronation moment to increase or a supination moment to decrease during
      the contact and propulsion phases of walking. With genu valgum, it was determined
      that during the contact phase a subtalar pronation moment would increase, whereas
      in the early propulsive phase, a subtalar supination moment would increase or a
      pronation moment would decrease. However, the current inability to track the
      spatial position of the subtalar joint axis makes it difficult to determine the
      absolute direction and magnitudes of the subtalar joint moments.

PMID- 16291845
TI  - Treatment of ingrown toenails using a new conservative method: a prospective
      study comparing brace treatment with Emmert's procedure.
AB  - Ingrown toenails cause incapacitation and pain for the patient and lost time from
      work. Many different conservative and surgical treatment methods have been
      described. European chiropodists and podologists have long treated ingrown
      toenails with orthonyxia, which consists of implantation of a small metal brace
      or plate onto the dorsum of the nail. To determine whether orthonyxia is an
      acceptable alternative to surgery, we compared the VHO-Osthold brace (VHO-Osthold
      Spange GmbH, Deisenhofen, Germany), a new method of orthonyxia, with Emmert's
      procedure, a standard surgical method that is virtually identical to the Winograd
      type procedure, in a prospective study of 41 patients (21 in the brace group and
      20 in the Emmert procedure group). Pain due to treatment was significantly lower
      in the brace group than in the Emmert procedure group, and patients in the brace
      group could wear regular shoes again without appreciable pain much earlier than
      those in the Emmert procedure group. In the brace group, there were four
      recurrences, and one patient was still receiving treatment at the end of follow
      up; in the Emmert procedure group, there were three recurrences. None of the
      patients in the brace group had to take time off from work, whereas in the Emmert
      procedure group, working patients were off from work for an average of 14.7 days.
      Brace treatment proved to be a good conservative alternative to operative
      procedures.

PMID- 16291846
TI  - Lesser-metatarsal medial displacement osteotomy for the treatment of digital
      transverse plane deformities.
AB  - We sought to evaluate the clinical and radiographic outcomes in patients treated
      with a medial displacement transverse osteotomy of the second metatarsal to
      correct transverse hammer toe deformities. Eighteen patients underwent 20
      procedures in 3 years. Each patient had a transverse plane deformity of the
      second metatarsophalangeal joint. Evaluation consisted of clinical examination,
      radiographic examination, and self-reported pain and function parameters. Mean +/
      SD follow-up was 2.5 +/- 1.0 years. Radiographic joint congruence improved from
      20% before surgery to 95% after surgery. Clinical examination revealed a rectus
      digit in 85% of cases, a transverse plane deviation in 10%, and a residual hammer
      toe deformity in 5%. At follow-up, the mean +/- SD visual analog scale score for
      pain with activity was 2.2 +/- 2.8 and for pain at rest was 0.6 +/- 1.4. Ninety
      five percent of the patients said that they would undergo the procedure again.
      Medial displacement osteotomy for transverse plane deformity of the second
      metatarsophalangeal joint is a reliable procedure, with substantial improvement
      in joint congruence and self-reported pain.

PMID- 16291847
TI  - Podiatric medical students' evaluation of a computerized student-patient
      encounter log system.
AB  - The computerized student-patient encounter log system represents a considerable
      improvement in terms of efficiency and accuracy over traditional paper-based
      student-patient encounter reporting systems. The computerized log not only
      facilitates faculty monitoring of students' assessment and management of health
      problems at geographically disparate locations but also provides a rich resource
      of data for enhancing clinical teaching and learning experiences. However, little
      is known about podiatric medical students' experiences with Web-based
      computerized student-patient encounter log systems. The findings reported in this
      article suggest that the computerized student-patient encounter log was
      considered to be useful and effective by most of the podiatric medical students
      surveyed and represents an improvement over traditional paper-based recording
      systems.

PMID- 16291848
TI  - Reliability of ankle goniometric measurements: a literature review.
AB  - This article reviews the existing range-of-motion measurement literature related
      to ankle dorsiflexion and plantarflexion to determine whether the reliability of
      ankle range-of-motion measurements can be defined, how the characteristics of the
      study population or clinician affect reliability, and the level of responsiveness
      for these measures. A MEDLINE search was performed through February 2004, and 11
      articles met the inclusion criteria established for this review. Ample evidence
      was found for intrarater reliability for ankle dorsiflexion and plantarflexion
      range of motion. Although some evidence for interrater reliability of
      dorsiflexion was found, little evidence for interrater reliability of
      plantarflexion range of motion was uncovered. On the basis of the current
      literature, the responsiveness of ankle joint range-of-motion measurements is
      uncertain and requires further studies using patient populations.

PMID- 16291849
TI  - Determinants of disabling foot pain in retirement village residents.
AB  - The aim of this study was to evaluate the relative contribution of structural
      foot characteristics and comorbidities to the presence of disabling foot pain in
      older people. One hundred seventy-two people (55 men and 117 women) aged 62 to 96
      years (mean +/- SD, 80.1 +/- 6.4 years) who lived in a retirement village
      underwent tests of foot posture, range of motion, and deformity in addition to
      completing a medical history questionnaire. Disabling foot pain was determined
      using the Manchester Foot Pain and Disability Index. Thirty-eight subjects (22%)
      reported disabling foot pain. Subjects with disabling foot pain had a higher body
      mass index and were more likely to be female; to report osteoarthritis in the
      spine, hips, hands or wrists, and feet; and to report pain in the back, hips, and
      hands or wrists. The only significant difference between the groups regarding
      structural foot characteristics was that those with disabling foot pain exhibited
      more severe hallux valgus deformity. The strongest determinants of disabling foot
      pain revealed by a discriminant function analysis were foot osteoarthritis, pain
      in the hips, and pain in the hands or wrists. These findings indicate that
      disabling foot pain in older people is more closely related to pain and
      osteoarthritis in other body regions than to structural characteristics of the
      foot, and they suggest that more severe forms of foot pain in older people may be
      a component of a general chronic pain syndrome or a polyarticular form of
      osteoarthritis.

PMID- 16291850
TI  - Callus formation of the tibial hallux sesamoid mimicking a bone tumor.
AB  - Sesamoid tumors of the hallux are rare, and their incidence and differential
      diagnosis have not been well described. We present a case with a bizarre callus
      formation of the medial sesamoid of the hallux that mimicked a bone tumor. After
      excision of the mass and related sesamoid, the patient remained asymptomatic
      during 3 years of follow-up.

PMID- 16291851
TI  - Os vesalianum pedis.
AB  - Os vesalianum pedis is an accessory bone located proximal to the base of the
      fifth metatarsal. Its prevalence has been reported to be from 0.1% to 1.0%. This
      bone is found within the peroneus brevis tendon and is considered to be
      asymptomatic in the majority of people. We describe a patient with os vesalianum
      pedis with a distinct mediocuboidal articulation. The radiologic differential
      diagnosis of the ossicle is discussed.

PMID- 16291852
TI  - Classic Kaposi's sarcoma.
AB  - Classic Kaposi's sarcoma is one form of Kaposi's sarcoma. It is usually first
      seen in the skin of the lower extremities, where it is frequently misdiagnosed as
      a bruise. As time progresses, the lesions increase in size, number, and color.
      Early diagnosis is paramount to decrease metastasis to other organ systems such
      as the lungs, kidneys, and liver. The podiatric physician must take a detailed
      history, follow the course of the illness, and be aware that definitive diagnosis
      is made by a skin biopsy. This article provides a case history of Kaposi's
      sarcoma and discusses diagnosis and treatment of this disease.

PMID- 16291853
TI  - New nail block technique.
AB  - This article presents a new nail block technique that constitutes an alternative
      local block for procedures involving the hallux nail and nail fold. It has
      significant advantages in terms of simplicity, effectiveness, safety, and economy
      over the traditional hallux block in selected procedures.

PMID- 16291855
TI  - Xanthoma of the calcaneus associated with hyperlipoproteinemia.

PMID- 16291854
TI  - Functional hallux limitus and lesser-metatarsal overload.
AB  - The implications of functional hallux limitus for lesser-metatarsal overload are
      discussed. A new method of treating functional hallux limitus is proposed, and
      three case histories are reviewed showing adequate resolution of symptoms using
      the proposed method of treatment. A proposed mechanism for the development of
      functional hallux limitus is discussed, and different methods of identification
      are illustrated.

PMID- 16291857
TI  - A new fixation technique for the Lapidus bunionectomy.

PMID- 16291859
TI  - Glutathione S-transferases M1/T1 gene polymorphisms and endometriosis: a meta
      analysis of genetic association studies.
AB  - In view of the controversies surrounding the glutathione S-transferases (GST)
      M1/T1-endometriosis association, a meta-analysis of the GSTM1/GSTT1 genetic
      association studies of endometriosis was performed. In this meta-analysis
      involving 14 GSTM1 studies with 1539 cases and 1805 controls and nine GSTT1
      studies with 746 cases and 834 controls, respectively, substantial
      heterogeneities among studies were found. In addition, asymmetry in funnel plot
      was evident, which is likely to stem from publication bias, given no apparent
      indication of true heterogeneity. The bias appears to be prominent for GSTM1
      studies, but is less so for GSTT1 studies. After correction for this bias, there
      is no evidence that women with GSTM1 null genotype have increased risk of
      developing endometriosis as compared with women with other genotypes. For GSTT1,
      the risk associated with the null genotype is 29% higher than other genotypes.
      However, even this estimate should be viewed with a large grain of salt, because
      the estimate could easily lose its statistical significance if there is a
      realistic 69-80% publication probability.

PMID- 16291861
TI  - G protein-coupled receptor Gpr4 senses amino acids and activates the cAMP-PKA
      pathway in Cryptococcus neoformans.
AB  - The Galpha protein Gpa1 governs the cAMP-PKA signaling pathway and plays a
      central role in virulence and differentiation in the human fungal pathogen
      Cryptococcus neoformans, but the signals and receptors that trigger this pathway
      were unknown. We identified seven putative proteins that share identity with
      known G protein-coupled receptors (GPCRs). One protein, Gpr4, shares limited
      sequence identity with the Dictyostelium discoideum cAMP receptor cAR1 and the
      Aspergillus nidulans GPCR protein GprH and also shares structural similarity with
      the Saccharomyces cerevisiae receptor Gpr1. gpr4 mutants exhibited reduced
      capsule production and mating defects, similar to gpa1 mutants, and exogenous
      cAMP suppressed both gpr4 mutant phenotypes. Epistasis analysis provides further
      evidence that Gpr4 functions upstream of the Galpha subunit Gpa1. Gpr4-Gpr4
      homomeric interactions were observed in the yeast two-hybrid assay, and Gpr4 was
      shown to physically interact with Gpa1 in the split-ubiquitin system. A
      Gpr4::DsRED fusion protein was localized to the plasma membrane and methionine
      was found to trigger receptor internalization. The analysis of intracellular cAMP
      levels showed that gpr4 mutants still respond to glucose but not to certain amino
      acids, such as methionine. Amino acids might serve as ligands for Gpr4 and could
      contribute to engage the cAMP-PKA pathway. Activation of the cAMP-PKA pathway by
      glucose and amino acids represents a nutrient coincidence detection system shared
      in other pathogenic fungi.

PMID- 16291860
TI  - Full-length dimeric MCAK is a more efficient microtubule depolymerase than
      minimal domain monomeric MCAK.
AB  - MCAK belongs to the Kinesin-13 family, whose members depolymerize microtubules
      rather than translocate along them. We defined the minimal functional unit of
      MCAK as the catalytic domain plus the class specific neck (MD-MCAK), which is
      consistent with previous reports. We used steady-state ATPase kinetics,
      microtubule depolymerization assays, and microtubule.MCAK cosedimentation assays
      to compare the activity of full-length MCAK, which is a dimer, with MD-MCAK,
      which is a monomer. Full-length MCAK exhibits higher ATPase activity, more
      efficient microtubule end binding, and reduced affinity for the tubulin
      heterodimer. Our studies suggest that MCAK dimerization is important for its
      catalytic cycle by promoting MCAK binding to microtubule ends, enhancing the
      ability of MCAK to recycle for multiple rounds of microtubule depolymerization,
      and preventing MCAK from being sequestered by tubulin heterodimers.

PMID- 16291862
TI  - Arp10p is a pointed-end-associated component of yeast dynactin.
AB  - In metazoans, dynein-dependent vesicle transport is mediated by dynactin,
      containing an actin-related protein, Arp1p, together with a cargo-selection
      complex containing a second actin-related protein, Arp11. Paradoxically, in
      budding yeast, models of dynactin function imply an interaction with membranes,
      whereas the lack of microtubule-based vesicle transport implies the absence of a
      cargo-selection complex. Using both genetic and biochemical approaches, we
      demonstrate that Arp10p is the functional yeast homologue of Arp11, suggesting
      the possible existence of a pointed-end complex in yeast. Specifically, Arp10p
      interacts with Arp1p and other dynactin subunits and is dependent on Arp1p for
      stability. Conversely, Arp10p stabilizes the dynactin complex by association with
      the Arp1p filament pointed end. Using a novel hRAS-Arp1p one-hybrid assay, we
      show that Arp1p associates with the plasma membrane dependent on dynactin
      subunits, but independent of dynein, and sensitive to cell wall damage. We
      directly show the association of Arp1p with not only the plasma membrane but also
      with a less dense membrane fraction. Based on the hRAS-Arp1p assay, loss of
      Arp10p enhances the apparent association of dynactin with the plasma membrane and
      suppresses the loss of signaling conferred by cell wall damage.

PMID- 16291863
TI  - Phospholipase D2 is required for efficient endocytic recycling of transferrin
      receptors.
AB  - RNA interference-mediated depletion of phospholipase D2 (PLD2), but not PLD1,
      inhibited recycling of transferrin receptors in HeLa cells, whereas the
      internalization rate was unaffected by depletion of either PLD. Although
      reduction of both PLD isoforms inhibits PLD activity stimulated by phorbol 12
      myristic 13-acetate, only depletion of PLD2 decreased nonstimulated activity.
      Cells with reduced PLD2 accumulated a greater fraction of transferrin receptors
      in a perinuclear compartment that was positive for Rab11, a marker of recycling
      endosomes. EFA6, an exchange factor for Arf6, has been proposed to stimulate the
      recycling of transferrin receptors. Thus, one consequence of EFA6 overexpression
      would be a reduction of the internal pool of receptors. We confirmed this
      observation in control HeLa cells; however, overexpression of EFA6 failed to
      decrease the internal pool of transferrin receptors that accumulate in cells
      previously depleted of PLD2. These observations suggest that either PLD2 is
      required for a constitutive Arf6-mediated recycling pathway or in the absence of
      PLD2 transferrin receptors accumulate in recycling endosomes that are not
      responsive to overexpression of EFA6.

PMID- 16291865
TI  - Nudel contributes to microtubule anchoring at the mother centriole and is
      involved in both dynein-dependent and -independent centrosomal protein assembly.
AB  - The centrosome is the major microtubule-organizing center in animal cells.
      Although the cytoplasmic dynein regulator Nudel interacts with centrosomes, its
      role herein remains unclear. Here, we show that in Cos7 cells Nudel is a mother
      centriole protein with rapid turnover independent of dynein activity. During
      centriole duplication, Nudel targets to the new mother centriole later than
      ninein but earlier than dynactin. Its centrosome localization requires a C
      terminal region that is essential for associations with dynein, dynactin,
      pericentriolar material (PCM)-1, pericentrin, and gamma-tubulin. Overexpression
      of a mutant Nudel lacking this region, a treatment previously shown to inactivate
      dynein, dislocates centrosomal Lis1, dynactin, and PCM-1, with little influence
      on pericentrin and gamma-tubulin in Cos7 and HeLa cells. Silencing Nudel in HeLa
      cells markedly decreases centrosomal targeting of all the aforementioned
      proteins. Silencing Nudel also represses centrosomal MT nucleation and anchoring.
      Furthermore, Nudel can interact with pericentrin independently of dynein. Our
      current results suggest that Nudel plays a role in both dynein-mediated
      centripetal transport of dynactin, Lis1, and PCM-1 as well as in dynein
      independent centrosomal targeting of pericentrin and gamma-tubulin. Moreover,
      Nudel seems to tether dynactin and dynein to the mother centriole for MT
      anchoring.

PMID- 16291864
TI  - Prox1 promotes lineage-specific expression of fibroblast growth factor (FGF)
      receptor-3 in lymphatic endothelium: a role for FGF signaling in
      lymphangiogenesis.
AB  - Fibroblast growth factors play important roles in angiogenesis, but their
      functions in lymphangiogenesis remain poorly understood. The homeodomain
      transcription factor Prox1 is essential for development of the lymphatic system
      by specifying lymphatic endothelial cell (LEC) fate. Here, we identify fibroblast
      growth factor (FGF) receptor (FGFR)-3 as a novel Prox1 target gene. Ectopic
      overexpression of Prox1 in blood vascular endothelial cells up-regulates FGFR-3.
      Prox1 induces the expression of the IIIc isoform, which we also found to be the
      major isoform of FGFR-3 expressed in LECs. This transcriptional activation is
      mediated by a direct binding of Prox1 to newly identified Prox1-response elements
      in the FGFR-3 promoter. Consistently, FGFR-3 is up-regulated in Prox1-positive
      newly formed lymphatic vessels during embryogenesis and its lymphatic-specific
      expression is maintained throughout development. We also found that FGF-1 and FGF
      2 promote proliferation, migration, and survival of cultured LECs without
      involvement of vascular endothelial cell growth factor receptor-3. We show that
      FGF-2 binds to low- and high-affinity receptors on LECs and is efficiently
      internalized and processed. Moreover, functional inhibition of FGFR-3 using small
      interfering RNA represses LEC proliferation. Together, these results indicate
      that FGFR-3 is an initial target of Prox1 during the lymphatic cell fate
      specification and that FGF signaling may play an important role in lymphatic
      vessel development.

PMID- 16291867
TI  - Macrolide resistance mechanisms and in vitro susceptibility patterns of viridans
      group streptococci isolated from blood cultures.
AB  - OBJECTIVES: Our aim was to study the macrolide resistance mechanisms and
      antimicrobial susceptibilities of viridans group streptococci (VGS) isolated from
      blood cultures. METHODS: In vitro susceptibilities to nine antimicrobials were
      studied for 85 VGS isolated from blood cultures by agar dilution. Pheno- and
      genotyping of erythromycin-resistant isolates were studied by the double disc
      test and PCR. RESULTS: Resistance to erythromycin was found in 27% (n = 23) of
      the isolates. Erythromycin-resistant Streptococcus oralis (n = 13) predominated
      among the other erythromycin-resistant species isolated. The phenotypes among 23
      erythromycin-resistant isolates were as follows: 12 constitutive macrolide
      lincosamide-streptogramin (cMLS(B)) resistance phenotype and 11 macrolide (M)
      resistance phenotype. Of the cMLS(B) isolates 11 had erm(B) genes and 11 of the M
      phenotype isolates had mef(A) genes. Four of the cMLS(B) isolates had both erm(B)
      and mef(A) genes. None of the isolates had erm(TR) genes. Combined resistance to
      erythromycin with penicillin, clindamycin, chloramphenicol, tetracycline and
      quinupristin/dalfopristin was found in 100, 61, 74, 100 and 100% of the isolates,
      respectively. No resistance was found for vancomycin, linezolid and levofloxacin.
      CONCLUSIONS: The macrolide resistance mechanisms of our VGS isolates revealed
      that the cMLS(B) phenotype associated with erm(B) and the M phenotype associated
      with mef(A) genes are found with similar frequencies.

PMID- 16291866
TI  - RhoA GTPase regulates M-cadherin activity and myoblast fusion.
AB  - The Rho family of GTP-binding proteins plays critical roles during myogenesis
      induction. To elucidate their role later during myogenesis, we have analyzed RhoA
      function during myoblast fusion into myotubes. We find that RhoA activity is
      rapidly and transiently increased when cells are shifted into differentiation
      medium and then is decreased until myoblast fusion. RhoA activity must be down
      regulated to allow fusion, because expression of a constitutively active form of
      RhoA (RhoAV14) inhibits this process. RhoAV14 perturbs the expression and
      localization of M-cadherin, a member of the Ca2+-dependent cell-cell adhesion
      molecule family that has an essential role in skeletal muscle cell
      differentiation. This mutant does not affect N-cadherin and other proteins
      involved in myoblast fusion, beta1-integrin and ADAM12. Active RhoA induces the
      entry of M-cadherin into a degradative pathway and thus decreases its stability
      in correlation with the monoubiquitination of M-cadherin. Moreover, p120 catenin
      association with M-cadherin is decreased in RhoAV14-expressing cells, which is
      partially reverted by the inhibition of the RhoA effector Rho-associated kinase
      ROCK. ROCK inhibition also restores M-cadherin accumulation at the cell-cell
      contact sites. We propose that the sustained activation of the RhoA pathway
      inhibits myoblast fusion through the regulation of p120 activity, which controls
      cadherin internalization and degradation.

PMID- 16291868
TI  - Antimicrobial peptides enhance the candidacidal activity of antifungal drugs by
      promoting the efflux of ATP from Candida cells.
AB  - OBJECTIVES: To establish a novel strategy of fungal infection control. METHODS:
      We examined the influences of antimicrobial peptides including a synthesized
      short lactoferrin peptide (FKCRRWQWRM, Peptide 2; Pep2) on the synthesis of
      Candida cell wall polysaccharides, ergosterol synthesis, membrane permeability
      and the efflux of ATP. RESULTS: Colony formation of Candida albicans was
      synergistically suppressed by a combination of low concentrations of each drug
      and peptide. All peptides and amphotericin B, but not itraconazole, revealed weak
      inhibitory activities against ergosterol synthesis and the peptides weakly
      suppressed the synthesis of Candida cell wall components, glucan, mannan and
      chitin. Cell membrane permeability was not only increased by these peptides but
      also clearly increased by both amphotericin B and itraconazole. ATP efflux was
      however up-regulated by low concentrations of the peptides, especially by Pep2
      and Hst5, although both antifungal drugs did not exert any influence on ATP
      efflux. The expression of the Candida drug resistance genes 1 and 2 (CDR1 and
      CDR2) was increased by both drugs, but this increase was suppressed by each
      peptide. In addition, larger amounts of amphotericin B and itraconazole remained
      in Candida cells in the presence of Pep2 or Hst5 due to the lower excretion. The
      effects of both peptides on ATP efflux and increase of intercellular amphotericin
      B and itraconazole were blocked by anion channel inhibitors 4,4'
      diisothiocyanatestilbene-2, 2'-disulphonic acid and 5-nitro-2-(3
      phenylpropylamino) benzoic acid. CONCLUSIONS: The examined peptides, especially
      Pep2 and Hst5, enhance the candidacidal activity of antifungal drugs by promoting
      anion channel-associated ATP efflux from Candida cells and decreasing efflux of
      the drugs, which could be useful clinical applications.

PMID- 16291869
TI  - DNA sequence analysis of the genetic environment of various blaCTX-M genes.
AB  - OBJECTIVES: Over a 3 year period (2000-2003) 21 Escherichia coli, 5 Klebsiella
      pneumoniae, 1 Serratia marcescens and 1 Proteus mirabilis producing CTX-M-type
      beta-lactamase were collected from five different hospitals in Paris, France.
      This study was conducted to analyse the genetic environment of these 28 bla(CTX
      M) genes. METHODS: Antimicrobial susceptibility testing was performed by the disc
      diffusion method and MICs of various beta-lactams were determined by an agar
      dilution method. PCR was used to detect and sequence alleles encoding CTX-M, TEM,
      SHV and CMY enzymes. The genetic environment was analysed by amplification and
      direct sequencing using various set of PCR primers or cloning in pBK-CMV.
      RESULTS: Sequence analysis revealed that these isolates contained seven different
      bla(CTX-M) genes: bla(CTX-M-1) (4 strains), bla(CTX-M-2) (2 strains), bla(CTX-M
      3) (4 strains), bla(CTX-M-9) (1 strain), bla(CTX-M-14) (5 strains), bla(CTX-M-15)
      (11 strains), bla(CTX-M-24) (1 strain). TEM-1 was associated with CTX-M-type
      enzymes in 15 isolates. Two strains produced both CTX-M-15 and SHV-2 or CTX-M-14
      and CMY-2. In 25 strains the insertion sequence ISEcp1 was located upstream of
      the 5' end of the bla(CTX-M) gene. Among these strains, in five isolates, ISEcp1
      was disrupted by insertion sequences such as IS26 (in three of them) or IS1 or
      IS10. Insertion sequence IS903 was found downstream of bla(CTX-M-14) or bla(CTX-M
      24). Examination of the other three bla(CTX-M) genes (two bla(CTX-M-2) and one
      bla(CTX-M-9)) by cloning, sequencing and PCR analysis revealed the presence of
      complex Class 1 integrons, In35, an integron similar to In60 and a novel
      integron. CONCLUSIONS: This work further confirmed the predominant role of ISEcp1
      in the mobilization of bla(CTX-M) genes of the CTX-M-1 cluster and the presence
      of In35, of an integron similar to In60 and a novel complex Class 1 integron.

PMID- 16291870
TI  - Natriuretic peptides, their receptors, and cyclic guanosine monophosphate
      dependent signaling functions.
AB  - Natriuretic peptides are a family of structurally related but genetically
      distinct hormones/paracrine factors that regulate blood volume, blood pressure,
      ventricular hypertrophy, pulmonary hypertension, fat metabolism, and long bone
      growth. The mammalian members are atrial natriuretic peptide, B-type natriuretic
      peptide, C-type natriuretic peptide, and possibly osteocrin/musclin. Three single
      membrane-spanning natriuretic peptide receptors (NPRs) have been identified. Two,
      NPR-A/GC-A/NPR1 and NPR-B/GC-B/NPR2, are transmembrane guanylyl cyclases, enzymes
      that catalyze the synthesis of cGMP. One, NPR-C/NPR3, lacks intrinsic enzymatic
      activity and controls the local concentrations of natriuretic peptides through
      constitutive receptor-mediated internalization and degradation. Single allele
      inactivating mutations in the promoter of human NPR-A are associated with
      hypertension and heart failure, whereas homozygous inactivating mutations in
      human NPR-B cause a form of short-limbed dwarfism known as acromesomelic
      dysplasia type Maroteaux. The physiological effects of natriuretic peptides are
      elicited through three classes of cGMP binding proteins: cGMP-dependent protein
      kinases, cGMP-regulated phosphodiesterases, and cyclic nucleotide-gated ion
      channels. In this comprehensive review, the structure, function, regulation, and
      biological consequences of natriuretic peptides and their associated signaling
      proteins are described.

PMID- 16291871
TI  - CD38 expression is insensitive to steroid action in cells treated with tumor
      necrosis factor-alpha and interferon-gamma by a mechanism involving the up
      regulation of the glucocorticoid receptor beta isoform.
AB  - Evidence shows that the CD38 molecule, recently involved in the two main features
      of asthma, bronchial hyper-responsiveness and airway inflammation, could
      represent a new potential therapeutic target for asthma. In this study, we
      investigated whether glucocorticoid (GC), the most effective treatment for lung
      diseases, can affect CD38 expression in human airway smooth muscle (ASM) cells
      treated with different pro-inflammatory cytokines, such as tumor necrosis factor
      alpha (TNFalpha) and interferons (IFNs). We found that CD38 expression induced by
      TNFalpha alone was completely abrogated by fluticasone (100 nM), dexamethasone (1
      microM), or budesonide (100 nM). In contrast, the synergistic induction of CD38
      by the combination of TNFalpha with IFNgamma or IFNbeta, but not with IL-1beta or
      IL-13, was completely insensitive to the GC inhibitory effects. We also found
      that TNFalpha and IFNgamma impaired GC responsiveness by inhibiting steroid
      induced both 1) GRalpha-DNA binding activity and 2) GC-responsive element-(GRE)
      dependent gene transcription. Although levels of the GC receptor (GR) alpha
      isoform remained unchanged, expression of GRbeta, the dominant-negative GR
      isoform, was synergistically increased by TNFalpha and IFNgamma with a
      GRalpha/GRbeta ratio of 1 to 3. More importantly, fluticasone failed to induce
      GRE-dependent gene transcription and to suppress TNFalpha-induced CD38 expression
      in ASM cells transfected with constitutively active GRbeta. We conclude that,
      upon pro-inflammatory cytokine stimulation, CD38 expression becomes insensitive
      to GC action by a mechanism involving the up-regulation of GRbeta isoform, thus
      providing a novel in vitro cellular model to dissect GC resistance in primary
      cells.

PMID- 16291872
TI  - Positive inter-regulation between beta-catenin/T cell factor-4 signaling and
      endothelin-1 signaling potentiates proliferation and survival of prostate cancer
      cells.
AB  - Both malignant and normal prostate epithelial cells produce endothelin-1 (ET-1),
      a critical factor in prostate cancer (CaP) progression. beta-Catenin (beta-cat),
      a key component of the Wnt signaling pathway, is also implicated in CaP
      progression via beta-cat/T cell factor (Tcf) signaling. We recently demonstrated
      that beta-cat/Tcf-4 regulates transcription of ET-1 in colon cancer cells. In the
      present study, we found that Tcf-4 specifically bound to and activated the ET-1
      promoter in vivo in human CaP cells and mouse prostate tissue. Expression of ET-1
      in DU145 CaP cells was down-regulated by knocking down endogenous beta-cat or Tcf
      4. Ectopic activation of beta-cat/Tcf-4 signaling significantly elevated
      expression of ET-1 in LNCaP cells. In addition, genetic ablation of beta-cat
      significantly inhibited transcription of ET-1 in primary prostate epithelial
      cells. Meanwhile, exogenous ET-1 enhanced beta-cat/Tcf signaling and ET-1
      expression in DU145 cells, which was blocked by both selective
      phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(4-morpholinyl)-8-phenyl-4H-1
      benzopyran-4-one (LY294002) and endothelin-A receptor antagonist cyclo(L-Leu-D
      Trp-D-Asp-L-Pro-D-Val) (BQ123). Furthermore, knockdown of either beta-cat or Tcf
      4 substantially reduced cell proliferation and potentiated paclitaxel-induced
      apoptosis in DU145 cells, which largely were rescued by treatment with exogenous
      ET-1. Together, our results suggest that beta-cat/Tcf-4 signaling
      transcriptionally activates ET-1 in CaP cells; meanwhile, ET-1 enhances beta
      cat/Tcf-4 signaling and in turn further increases ET-1 expression in a PI3K
      dependent manner. The positive inter-regulation between beta-cat/Tcf-4 signaling
      and ET-1 signaling potentiates proliferation and survival of CaP cells, thereby
      representing a novel mechanism that contributes to CaP progression.

PMID- 16291873
TI  - Drug binding interactions in the inner cavity of HERG channels: molecular
      insights from structure-activity relationships of clofilium and ibutilide
      analogs.
AB  - Block of human ether-a-go-go related gene (hERG) K(+) channels by otherwise
      useful drugs is the most common cause of long QT syndrome, a disorder of cardiac
      repolarization that predisposes patients to potentially fatal arrhythmias. This
      undesirable long QT side effect has been a major reason for the withdrawal of
      medications from the pharmaceutical market. Understanding the molecular basis of
      hERG block is therefore essential to facilitate the design of safe drugs. Binding
      sites for hERG blockers have been mapped within the inner cavity of the channel
      and include aromatic residues in the S6 helix (Tyr-652, Phe-656) and residues in
      the pore helix (Thr-623, Ser-624, Val-625). We used mutagenesis of these
      residues, combined with an investigation of hERG block by close analogs of
      clofilium and ibutilide, to assess how specific alterations in drug structure
      affected potency and binding interactions. Although changing the basic nitrogen
      from quaternary to tertiary accelerated the onset of block, the IC(50) and
      kinetics for recovery from block were similar. In contrast, analogs with
      different para-substituents on the phenyl ring had significantly different
      potencies for wild-type hERG block. The highest potency was achieved with polar
      or electronegative para-substituents, whereas neutral para-substituents had
      potencies more than 100-fold lower. Results from mutagenesis and molecular
      modeling studies suggest that phenyl ring para-substituents influence drug
      interactions with Thr-623, Ser-624, and Tyr-652 and strongly affect binding
      affinity. Together, these findings suggest that modifying the para-substituent
      could be a useful strategy for reducing hERG potency and increasing the safety
      margin of compounds in development.

PMID- 16291874
TI  - Growth hormone determines sexual dimorphism of hepatic cytochrome P450 3A4
      expression in transgenic mice.
AB  - The impact of age and sex on the expression of hepatic cytochrome P450 3A4
      (CYP3A4) was recently determined in a transgenic mouse line carrying the human
      CYP3A4 gene. To further investigate the physiological regulation of human CYP3A
      genes, a novel transgenic mouse line was generated using a bacterial artificial
      chromosome clone containing both CYP3A4 and CYP3A7 genes. CYP3A7 expression was
      observed in transgenic mouse fetal livers, whereas CYP3A4 exhibited developmental
      expression characterized by sexual dimorphism in postpubertal livers. Hepatic
      CYP3A4 protein and RNA were expressed in immature transgenic male mice and became
      undetectable after 6 weeks of age, whereas CYP3A4 was expressed in both immature
      and adult females. CYP3A4 was markedly elevated by the xenobiotic receptor
      activator phenobarbital in both male and female livers, demonstrating drug
      induction of the CYP3A4 transgene in this mouse model. Furthermore, continuous
      infusion of recombinant growth hormone (GH) in transgenic male mice, overriding
      the pulsatile male plasma GH profile, increased hepatic CYP3A4 mRNA and protein
      to normal female levels. Continuous GH treatment also feminized the expression of
      endogenous murine Cyp2b and Cyp3a44 genes. Thus, human CYP3A4 contains all of the
      gene regulatory sequences required for it to respond to endogenous hormonal
      regulators of developmental expression and sexual dimorphism, in particular GH.
      These findings may help elucidate the role of GH in determining the sex-dependent
      expression of CYP3A4 in human liver and suggest that GH therapy may alter the
      pharmacokinetic and pharmacodynamic properties of CYP3A4 substrates, leading to
      enhanced metabolism and disposition of drugs in men.

PMID- 16291875
TI  - Comparison of the antinociceptive response to morphine and morphine-like
      compounds in male and female Sprague-Dawley rats.
AB  - Male rats are more sensitive to the antinociceptive effects of morphine than
      female rats. This difference is seen across several rat strains using a variety
      of nociceptive stimuli. However, the literature in regard to sex differences in
      antinociceptive responses to mu-opioids other than morphine is less consistent.
      The present study was designed to examine whether there is a structure-activity
      rationale that determines which mu-opioids will show a differential
      antinociceptive response between male and female rats. A series of morphinans
      closely related in structure to morphine, namely, codeine, heroin, hydrocodone,
      hydromorphone, oxymorphone, and oxycodone, were examined for their
      antinociceptive activity in male and female Sprague-Dawley rats and compared with
      the structurally unrelated mu-opioid agonists methadone and fentanyl.
      Antinociception was measured by the warm-water tail-withdrawal assay. The results
      show that morphine is more potent in males compared with females > hydromorphone
      = hydrocodone = oxymorphone, but there was no observable sex difference in the
      antinociceptive potency of codeine, heroin, oxycodone, methadone, or fentanyl.
      The potency to stimulate guanosine 5'-O-(3-[35 S]thio)triphosphate
      ([35S]GTPgammaS) binding and binding affinity of the various morphinans was
      compared in rat glioma C6 cells expressing the rat mu-opioid receptor; relative
      efficacy was also compared by stimulation of [35S]GTPgammaS binding in slices of
      rat brain thalamus. The presence of a sex difference in antinociceptive
      responsiveness was not related to drug potency, efficacy, or affinity.
      Consequently, it is likely that differential metabolism of the opioid, possibly
      by glucuronidation, determines the presence or absence of a sex difference.

PMID- 16291876
TI  - Is the monkey an appropriate animal model to examine drug-drug interactions
      involving renal clearance? Effect of probenecid on the renal elimination of H2
      receptor antagonists.
AB  - The renal drug-drug interaction between famotidine (an H(2) receptor antagonist)
      and probenecid has not been reproduced in rats. We have proposed that this is
      caused by a species difference in the transport activity by human/rat organic
      anion transporter (OAT) 3 and the expression of organic cation transporter (OCT)
      1 in the rodent kidney. Since monkey OATs (mkOATs) exhibit similar transport
      activities to human orthologs, it is hypothesized that in vivo studies in monkeys
      will allow a more precise prediction of renal drug-drug interactions in humans.
      Famotidine and cimetidine were efficiently taken up by mkOAT3-expressing human
      embryonic kidney cells (Km, 154 and 71 microM, respectively), and their uptake
      was strongly inhibited by probenecid (Ki, 3.0-5.7 microM). Quantification of
      mkOCT1 and mkOCT2 mRNAs in the monkey kidney using real-time reverse
      transcription-polymerase chain reaction revealed their predominant expression in
      the liver and kidney, respectively. Crossover studies were conducted in
      cynomolgus monkeys. Famotidine was given by i.v. administration, with or without
      probenecid. Probenecid treatment caused a 65% reduction in the renal clearance
      (0.426 +/- 0.079 versus 0.165 +/- 0.027 l/h/kg) and a 90% reduction in the
      tubular secretion clearance (0.275 +/- 0.075 versus 0.0230 +/- 0.0217 l/h/kg),
      whereas it had no effect on the renal clearance of cimetidine. In contrast to the
      species-dependent effect of probenecid, allometric scaling using animal data
      (rat, dog, and monkey) successfully predicted the renal and tubular secretion
      clearance of famotidine in humans. These results suggest that monkeys are more
      appropriate animal species for predicting the renal drug-drug interactions in
      humans.

PMID- 16291879
TI  - Lipid lowering agents to delay cognitive decline in Alzheimer's disease?

PMID- 16291877
TI  - Comments on "acetaminophen and the cyclooxygenase-3 puzzle: sorting out facts,
      fictions, and uncertainties".

PMID- 16291880
TI  - Cannabinoids in multiple sclerosis: urgent need for long term trials.

PMID- 16291881
TI  - Withdrawal of antiepileptic drugs in people with non-epileptic seizures.

PMID- 16291882
TI  - Non-invasive brain stimulation for Parkinson's disease: a systematic review and
      meta-analysis of the literature.
AB  - A systematic review and meta-analysis were conducted to quantify the efficacy of
      transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT) for
      the treatment of motor dysfunction in patients with Parkinson's disease (PD).
      Prospective studies which evaluated the effects of either TMS (12 studies) or ECT
      (five studies) on motor function in PD using the motor subscale of the Unified
      Parkinson's Disease Rating Scale (UPDRS) for TMS studies and any continuous
      measures of motor function in PD for ECT studies were included. The pooled effect
      size (standardised mean difference between pre-treatment versus post-treatment
      means) from a random effects model was 0.62 (95% confidence interval: 0.38, 0.85)
      for TMS treatment and 1.68 (0.79, 2.56) for ECT treatment, and from a fixed
      effects model was 0.59 (0.39, 0.78) for TMS treatment and 1.55 (1.07, 2.03) for
      ECT treatment. TMS, across applied stimulation sites and parameters, can exert a
      significant, albeit modest, positive effect on the motor function of patients
      with PD. ECT also may exert a significant effect on motor function in PD
      patients.

PMID- 16291883
TI  - Lipid lowering agents are associated with a slower cognitive decline in
      Alzheimer's disease.
AB  - BACKGROUND: Data from epidemiological studies and animal models imply that
      disturbances in cholesterol metabolism are linked to Alzheimer's disease
      susceptibility. Lipid lowering agents (LLAs) may have implications for the
      prevention of Alzheimer's disease. OBJECTIVE: To investigate whether LLAs are
      associated with a slower cognitive decline in Alzheimer's disease. METHODS: An
      observational study in 342 Alzheimer patients followed in a memory clinic for
      34.8 months (mean age 73.5 years, mini-mental state examination score (MMSE) 21.3
      at entry); 129 were dyslipaemic treated with LLAs (47% with statins), 105 were
      untreated dyslipaemic, and 108 were normolipaemic. The rate of cognitive decline
      was calculated as the difference between the first and last MMSE score, divided
      by the time between the measurements, expressed by year. Patients were divided
      into slow and fast decliners according to their annual rate of decline (lower or
      higher than the median annual rate of decline in the total population). RESULTS:
      Patients treated with LLAs had a slower decline on the MMSE (1.5 point/year, p =
      0.0102) than patients with untreated dyslipaemia (2.4 points/year), or
      normolipaemic patients (2.6 points/year). Patients with a slower decline were
      more likely to be treated with LLAs. Logistic regression analysis, with low
      annual cognitive decline as the dependent variable, showed that the independent
      variable LLA (treated with or not) was positively associated with the probability
      of lower cognitive decline (odds ratio = 0.45, p = 0.002). CONCLUSIONS: LLAs may
      slow cognitive decline in Alzheimer's disease and have a neuroprotective effect.
      This should be confirmed by placebo controlled randomised trials in patients with
      Alzheimer's disease and no dyslipaemia.

PMID- 16291884
TI  - Metacognitive deficits in frontotemporal dementia.
AB  - OBJECTIVES: To investigate whether metacognitive impairments in self-awareness
      and self-monitoring occur in patients with frontotemporal dementia (FTD),
      particularly among those with prominent social and dysexecutive impairments.
      METHODS: Patients diagnosed with FTD were divided by clinical subtype (social
      dysexecutive (n = 12) aphasic (n = 15), and constituent subgroups of progressive
      non-fluent aphasia and semantic dementia) and compared with subjects with
      probable Alzheimer's disease (AD, n = 11) and age-matched healthy controls (n =
      11). All subjects completed comprehensive behavioural ratings scales, which were
      compared with caregiver ratings. Subjects also rated their test performances in
      verbal associative fluency, word list learning, and memory task with comparisons
      made between actual and judged performance levels. RESULTS: The FTD sample as a
      whole showed significantly less behavioural self-awareness and self-knowledge
      than the AD and healthy control samples. FTD patients with prominent social and
      dysexecutive impairments demonstrated the most extensive loss of self-awareness
      and self-knowledge, significantly overrating themselves in multiple social,
      emotional, and cognitive domains, and failing to acknowledge that any behavioural
      change had occurred in most areas. The remaining clinical samples showed select
      and minimal discrepancies. All clinical groups were significantly unaware of
      their apathy levels. Most FTD patients judged episodic cognitive test performance
      adequately, with partial difficulties observed in the socially impaired and
      progressive non-fluent aphasia subgroups. CONCLUSIONS: FTD patients, particularly
      those with prominent social and dysexecutive impairments, exhibit profound
      metacognitive anosognosia that may represent a loss of self-awareness, self
      monitoring, and self-knowledge, likely related to significant prefrontal
      pathophysiology. Other FTD clinical groups and AD patients showed less pervasive
      and more select metacognitive deficiencies.

PMID- 16291885
TI  - Modafinil for daytime somnolence in Parkinson's disease: double blind, placebo
      controlled parallel trial.
AB  - BACKGROUND: Excessive daytime somnolence (EDS) commonly complicates Parkinson's
      disease (PD). The aetiology of EDS is probably multifactorial but is probably
      exacerbated by dopaminergic medications. Modafinil is a wake-promoting agent
      approved for use in narcolepsy, but it is often used to treat a variety of
      somnolent conditions. METHOD: A double blind, placebo controlled parallel design
      trial was conducted to assess the efficacy of modafinil (200-400 mg/day) for the
      treatment of EDS in PD. The primary efficacy measure was the Epworth Sleepiness
      (ES) scale score. Secondary efficacy points included the Unified Parkinson's
      Disease Rating Scale (UPDRS), the Fatigue Severity Scale, the Hamilton Depression
      Scale, and the multiple sleep latency test (MSLT). RESULTS: Of a total of 40
      subjects (29 men, mean (SD) age 64.8 (11.3) years), randomised to modafinil or
      placebo, 37 completed the study. Modafinil failed to significantly improve ES
      scores compared with placebo (2.7 v 1.5 points improvement, respectively, p =
      0.28). MSLT failed to improve with modafinil relative to placebo (-0.16 v -0.70,
      respectively, p = 0.14). UPDRS, global impressions, Fatigue Severity Scale, and
      Hamilton Depression Scale scores were unchanged. Adverse events were minimal.
      CONCLUSION: Modafinil failed to significantly improve EDS in PD compared with
      placebo. The drug did not alter motor symptoms in PD and was well tolerated.

PMID- 16291886
TI  - Stimulation of the subthalamic nucleus in Parkinson's disease: a 5 year follow
      up.
AB  - BACKGROUND: The short term benefits of bilateral stimulation of the subthalamic
      nucleus (STN) in patients with advanced levodopa responsive Parkinson's disease
      (PD) are well documented, but long term benefits are still uncertain. OBJECTIVES:
      This study provides a 5 year follow up of PD patients treated with stimulation of
      the STN. METHODS: Thirty seven consecutive patients with PD treated with
      bilateral STN stimulation were assessed prospectively 6, 24, and 60 months after
      neurosurgery. Parkinsonian motor disability was evaluated with and without
      levodopa treatment, with and without bilateral STN stimulation.
      Neuropsychological and mood assessments included the Mattis Dementia Rating
      Scale, the frontal score, and the Montgomery-Asberg Depression Rating Scale
      (MADRS). RESULTS: No severe peri- or immediate postoperative side effects were
      observed. Six patients died and one was lost to follow up. Five years after
      neurosurgery: (i) activity of daily living (Unified Parkinson Disease Rating
      Scale (UPDRS) II) was improved by stimulation of the STN by 40% ("off" drug) and
      60% ("on" drug); (ii) parkinsonian motor disability (UPDRS III) was improved by
      54% ("off" drug) and 73% ("on" drug); (iii) the severity of levodopa related
      motor complications was decreased by 67% and the levodopa daily doses were
      reduced by 58%. The MADRS was unchanged, but cognitive performance declined
      significantly. Persisting adverse effects included eyelid opening apraxia, weight
      gain, addiction to levodopa treatment, hypomania and disinhibition, depression,
      dysarthria, dyskinesias, and apathy. CONCLUSIONS: Despite moderate motor and
      cognitive decline, probably due to disease progression, the marked improvement in
      motor function observed postoperatively was sustained 5 years after neurosurgery.

PMID- 16291887
TI  - When is Onuf's nucleus involved in multiple system atrophy? A sphincter
      electromyography study.
AB  - BACKGROUND: External anal sphincter (EAS) electromyography (EMG) abnormalities
      can distinguish multiple system atrophy (MSA) from Parkinson's disease in the
      first five years after disease onset. However, the prevalence of the
      abnormalities in the early stages of MSA is unknown. OBJECTIVES: To present EAS
      EMG data in the various stages of MSA. METHODS: 84 patients with "probable" MSA
      were recruited (42 men, 42 women; mean age 62 years (range 47 to 78); mean
      disease duration 3.2 years (0.5 to 8.0; <1 year in 25%); 50 cerebellar form (MSA
      C), 34 parkinsonian form (MSA-P)). EAS motor unit potential (MUP) analysis and
      EMG cystometry were carried out in all patients. RESULTS: The overall prevalence
      of neurogenic change of the EAS MUP was 62%-52% in the first year after disease
      onset, increasing to 83% by the fifth year (p<0.05); it also increased with
      severity of gait disturbance (p<0.05), storage and voiding disorders, and
      detrusor sphincter dyssynergy (NS). The neurogenic change was not correlated with
      sex, age, MSA-P/C, postural hypotension, constipation, erectile dysfunction in
      men, underactive or acontractile detrusor, or detrusor overactivity. In 17
      incontinent patients without detrusor overactivity or low compliance, urinary
      incontinence was more severe in those with neurogenic change than in those
      without (p<0.05). CONCLUSIONS: Involvement of Onuf's nucleus in MSA is time
      dependent. Before the fifth year of illness, the prevalence of neurogenic change
      does not seem to be high, so a negative result cannot exclude the diagnosis of
      MSA.

PMID- 16291888
TI  - Influence of pre-existing dementia on the risk of post-stroke epileptic seizures.
AB  - BACKGROUND: Seizures occur in 10% of stroke patients, but their predictors have
      not been clearly identified. Pre-existing dementia is present in 12-16% of stroke
      patients and, at the community level, patients with dementia have increased risk
      of seizures. However, the question of whether pre-existing dementia is associated
      with a higher risk of seizures after stroke has never been studied. AIM: To
      evaluate whether pre-existing dementia is associated with an increased risk of
      seizures after stroke. METHODS: The study was conducted on 202 consecutive stroke
      patients recruited to the Lille stroke/dementia study (97 men; median age, 75
      years; range, 42-100). Pre-stroke cognitive functions were evaluated using the
      Informant Questionnaire on Cognitive Decline in the Elderly, with a cutoff value
      of 104 for the diagnosis of dementia. Seizures were defined as early seizures
      when occurring within seven days of stroke onset, and as late seizures when
      occurring more than seven days after stroke. RESULTS: Of 202 patients, 33 (16.3%)
      met the criteria for pre-existing dementia, and 11 (5.4%) developed early
      seizures. During 289 person-years of follow up, 14 patients developed late
      seizures, resulting in an incidence rate of 4.8 new cases/100 person-years. Pre
      existing dementia was not associated with the occurrence of early seizures, but
      was independently associated with the occurrence of late seizures (adjusted odds
      ratio, 4.66; 95% confidence interval, 1.34 to 16.21). CONCLUSION: Stroke patients
      with pre-existing dementia have an increased risk of late seizures. Any factor
      increasing the risk of seizures (drugs, metabolic changes) should be avoided in
      these patients.

PMID- 16291889
TI  - Do stroke patients with normal carotid arteries require TEE for exclusion of
      relevant aortic plaques?
AB  - OBJECTIVES: This study investigated (a) the hypothesis that stroke patients with
      aortic atheroma would show comparable atherosclerotic changes in the carotid
      arteries, which are easily accessible for ultrasound evaluation and (b) the
      possibility of carotid duplex sonography as a replacement for transoesophageal
      echocardiography (TEE) for the exclusion or prediction of relevant aortic
      plaques. METHODS: In 301 consecutive patients (mean age 62 years) with acute
      cerebral ischaemia, two dimensional ultrasound measurements were taken of common
      carotid artery intima media thickness (IMT) and maximal plaque area (PA) and the
      local degree of internal carotid artery (ICA) stenosis were determined. Maximal
      aortic wall thickness (AWT) was assessed by TEE. RESULTS: An IMT < or =0.9 mm
      yielded a negative predictive value (NPV) of 95.8% for exclusion of aortic
      atheromas > or =4 mm and an NPV of 100% for the exclusion of aortic thrombi.
      However, positive predictive value of IMT >0.9 mm was low (29.6%), increasing
      only slightly in the presence of carotid plaques (33%). Incidence of aortic
      thrombi was significantly higher with > or =50% compared with <50% ICA stenosis
      (11.3% v 3.9%, respectively). IMT and PA correlated moderately with AWT (r =
      0.47, r = 0.53, respectively; p<0.001). Systolic blood pressure, coronary heart
      disease and peripheral artery disease, increased IMT, and ICA stenosis > or =50%
      were independently related to AWT > or =4 mm. CONCLUSIONS: A high NPV of normal
      carotid ultrasound does not support routine TEE for the exclusion of complex
      aortic plaques as a high risk source of cerebral embolism. However, in patients
      with carotid atherosclerosis, particularly in those with ICA stenosis > or =50%,
      TEE should be performed to exclude an additional high risk source for stroke.

PMID- 16291890
TI  - Pathogenesis of deep white matter medullary infarcts: a diffusion weighted
      magnetic resonance imaging study.
AB  - BACKGROUND AND PURPOSE: The pathogenesis of deep white matter medullary (WMM)
      artery infarcts remains controversial. To address this question, we analysed the
      stroke patterns of WMM infarcts using diffusion weighted magnetic resonance
      imaging (DWI) to detect embolic signals and investigate stroke subtypes according
      to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classifications.
      METHODS: We identified WMM infarcts on DWI using templates to determine the
      subcortical vascular territories. We classified WMM infarcts into those with
      small artery disease (SAD), large artery disease (LAD), cardioembolism (CE), two
      or more aetiologies, or undetermined aetiology. Clinical course, risk factors,
      and cortical spotty lesions were compared. RESULTS: Of the 1420 consecutive
      patients, 103 (7.3%) met the criteria for WMM infarcts. The stroke subtypes were
      as follows: 65 (63.1%) patients with LAD, 18 (17.5%) with SAD, 12 (11.7%) with
      CE, four (3.9%) with two or more aetiologies, three (2.1%) with undetermined
      aetiology, and one (1.0%) with other determined aetiology. LAD (87.7%) or CE
      (83.3%) was significantly accompanied by cortical embolic signals as compared to
      SAD (0%, p<0.001). The LAD infarcts were larger and tended to be chain-like in
      shape. Ischaemic stroke recurrence was more common in strokes with cortical
      embolic signals than in those without embolic signals (18.9% v 0%, p = 0.009).
      CONCLUSIONS: In present study, the most common pathogenesis of WMM infarcts was
      LAD. Our study indicates that WMM infarcts accompanying cortical embolic signals
      warrant evaluation of the underlying embolic sources in the large artery or the
      heart.

PMID- 16291891
TI  - Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12
      months follow up.
AB  - OBJECTIVE: To test the effectiveness and long term safety of cannabinoids in
      multiple sclerosis (MS), in a follow up to the main Cannabinoids in Multiple
      Sclerosis (CAMS) study. METHODS: In total, 630 patients with stable MS with
      muscle spasticity from 33 UK centres were randomised to receive oral Delta(9)
      tetrahydrocannabinol (Delta(9)-THC), cannabis extract, or placebo in the main 15
      week CAMS study. The primary outcome was change in the Ashworth spasticity scale.
      Secondary outcomes were the Rivermead Mobility Index, timed 10 metre walk, UK
      Neurological Disability Score, postal Barthel Index, General Health Questionnaire
      30, and a series of nine category rating scales. Following the main study,
      patients were invited to continue medication, double blinded, for up to 12 months
      in the follow up study reported here. RESULTS: Intention to treat analysis of
      data from the 80% of patients followed up for 12 months showed evidence of a
      small treatment effect on muscle spasticity as measured by change in Ashworth
      score from baseline to 12 months (Delta(9)-THC mean reduction 1.82 (n = 154, 95%
      confidence interval (CI) 0.53 to 3.12), cannabis extract 0.10 (n = 172, 95% CI 
      0.99 to 1.19), placebo -0.23 (n = 176, 95% CI -1.41 to 0.94); p = 0.04 unadjusted
      for ambulatory status and centre, p = 0.01 adjusted). There was suggestive
      evidence for treatment effects of Delta(9)-THC on some aspects of disability.
      There were no major safety concerns. Overall, patients felt that these drugs were
      helpful in treating their disease. CONCLUSIONS: These data provide limited
      evidence for a longer term treatment effect of cannabinoids. A long term placebo
      controlled study is now needed to establish whether cannabinoids may have a role
      beyond symptom amelioration in MS.

PMID- 16291892
TI  - Placebo controlled, randomised, double blind study of the effects of botulinum A
      toxin on detrusor sphincter dyssynergia in multiple sclerosis patients.
AB  - OBJECTIVE: The purpose of the study was to evaluate the efficacy and safety of
      botulinum A toxin in the treatment of detrusor sphincter dyssynergia in multiple
      sclerosis patients. METHODS: This was a multicentre, placebo controlled,
      randomised, double blind study. Patients with chronic urinary retention were
      included if they had post-voiding residual urine volume between 100 and 500 ml.
      They received a single transperineal injection of either botulinum A toxin (100 U
      Allergan) or placebo in the sphincter and also 5 mg slow release alfuzosin bid
      over 4 months. Main endpoint was post-voiding residual urine volume assessed 1
      month after injection. Follow up duration was 4 months. Statistical analysis was
      performed using a sequential method, the triangular test. RESULTS: The study was
      stopped after the fourth analysis (86 patients had been included: placebo: 41,
      botulinum A toxin: 45). At inclusion, there was no significant difference between
      groups whichever variable was considered. Mean (standard deviation) post-voiding
      residual urine volume was 217 (96) and 220 (99) ml in placebo and botulinum A
      toxin groups, respectively. One month later, post-voiding residual urine volume
      was 206 (145) and 186 (158) ml (p = 0.45) in placebo and botulinum A toxin
      groups, respectively. However, compared to placebo, botulinum A toxin
      significantly increased voiding volume (+54%, p = 0.02) and reduced pre
      micturition (-29%, p = 0.02) and maximal (-21%, p = 0.02) detrusor pressures.
      Other secondary urodynamic endpoints and tolerance were similar in the two
      groups. CONCLUSIONS: In multiple sclerosis patients with detrusor sphincter
      dyssynergia, a single injection of botulinum A toxin (100 U Allergan) does not
      decrease post-voiding residual urine volume.

PMID- 16291893
TI  - Psychometric evaluation of the multiple sclerosis impact scale (MSIS-29) for
      proxy use.
AB  - BACKGROUND: There may be difficulties in the use of self report measurements in
      patients with cognitive impairment or serious mood disturbances which interfere
      with reliable self assessment, as may be the case in multiple sclerosis (MS). In
      such cases proxies may provide valuable information. However, before using any
      questionnaires in a proxy sample, the questionnaire should be evaluated for proxy
      use. OBJECTIVE: To evaluate the psychometric properties of the 29 item Multiple
      Sclerosis Impact Scale (MSIS-29) when used by proxies of MS patients. METHODS: A
      sample of 62 partners of MS patients completed the MSIS-29. The data were
      evaluated for the psychometric criteria of the MSIS-29, including data quality,
      scaling assumptions, acceptability, reliability, validity, and responsiveness.
      RESULTS: Psychometric evaluation was satisfactory; data quality was high, and
      scaling assumptions and acceptability were good. Reliability was high
      (alpha>0.80). Findings were consistent with results of a psychometric evaluation
      in a patient sample. CONCLUSIONS: The MSIS-29 can be used reliably in proxies of
      patients with MS. As a next step the relation between data obtained from patients
      and proxies needs to be studied, focusing on factors that may affect agreement
      and discrepancies.

PMID- 16291894
TI  - [11C]-Methionine PET: dysembryoplastic neuroepithelial tumours compared with
      other epileptogenic brain neoplasms.
AB  - BACKGROUND AND OBJECTIVES: Brain tumours responsible for longstanding partial
      epilepsy are characterised by a high prevalence of dysembryoplastic
      neuroepithelial tumour (DNT), whose natural evolution is much more benign than
      that of gliomas. The preoperative diagnosis of DNT, which is not yet feasible on
      the basis of available clinical and imaging data, would help optimise the
      therapeutic strategy for this type of tumour. This study tested whether [(11)C]
      methionine positron emission tomography (MET-PET) could help to distinguish DNTs
      from other epileptogenic brain tumours. METHODS: Prospective study of 27 patients
      with partial epilepsy of at least six months duration related to a non-rapidly
      progressing brain tumour on magnetic resonance imaging (MRI). A structured visual
      analysis, which distinguished between normal, moderately abnormal, or markedly
      abnormal tumour methionine uptake, as well as various regions of interest and
      semiquantitative measurements were conducted. RESULTS: Pathological results
      showed 11 DNTs (41%), 5 gangliogliomas (18%), and 11 gliomas (41%). MET-PET
      visual findings significantly differed between the various tumour types
      (p<0.0002), regardless of gadolinium enhancement on MRI, and were confirmed by
      semiquantitative analysis (p<0.001 for all calculated ratios). All gliomas and
      gangliogliomas were associated with moderately or markedly increased tumour
      methionine uptake, whereas 7/11 DNTs had a normal methionine uptake, including
      all six located in the mesiotemporal structures. No DNT presented with a marked
      MET-PET abnormality. CONCLUSION: Normal MET-PET findings in patient with an
      epileptogenic and non-rapidly progressing brain tumour are suggestive of DNT,
      whereas a markedly increased tumour methionine uptake makes this diagnosis
      unlikely.

PMID- 16291896
TI  - Peripheral neuropathy in metachromatic leucodystrophy. A study of 40 cases from
      south India.
AB  - BACKGROUND: There is a paucity of literature from India on metachromatic
      leucodystrophy (MLD), a rare metabolic disorder of childhood resulting from aryl
      sulfatase A (ASA) deficiency.Patients/ METHODS: Case records of
      histopathologically verified cases of MLD, evaluated over a period of 12 years at
      the National Institute of Mental Health and Neurosciences, Bangalore, India, were
      reviewed. RESULTS: The late infantile group (36) manifested with regression of
      milestones (all), delayed mile stones (14), gait abnormalities (14), and seizures
      (11). Despite spasticity (29), there was hypo/areflexia in 25 patients. Optic
      atrophy (six) was rare. Consanguinity was noted in 25 children and four had a
      history of similar illness in siblings. Behavioural problems dominated in the
      juvenile group (four), but associated cognitive decline and hyporeflexia provided
      a clue to the diagnosis. Low serum ASA (seven of 20), raised cerebrospinal fluid
      protein (five of 12), and urinary metachromatic granules (two of 32) were
      infrequent. Electrophysiological evidence of severe demyelinating and length
      dependent sensory motor neuropathy was observed in all, even in the presence of
      hyper-reflexia. In addition to metachromatic dysmyelinating neuropathy in all
      patients, sural nerve biopsy in 20 patients revealed orthochromatic deposits
      within perivascular macrophages, particularly among those patients with normal
      ASA values (11 of 14), suggesting the accumulation of other glycosphingolipids.
      CONCLUSIONS: This study produced some noteworthy observations: the high degree of
      consanguinity associated with MLD in India, the existence of MLD with normal
      serum concentrations of ASA, the deposition of orthochromatic lipids, and
      electrophysiological evidence of a partial conduction block.

PMID- 16291895
TI  - Clinical course, pathological correlations, and outcome of biopsy proved
      inflammatory demyelinating disease.
AB  - BACKGROUND: A pathological classification has been developed of early active
      multiple sclerosis (MS) lesions that reveals four patterns of tissue injury: I-T
      cell/macrophage associated; II-antibody/complement associated; III-distal
      oligodendrogliopathy, and IV-oligodendrocyte degeneration in the periplaque white
      matter. Mechanisms of demyelination in early MS may differ among the subgroups.
      Previous studies on biopsied MS have lacked clinicopathological correlation and
      follow up. Critics argue that observations are not generalisable to prototypic
      MS. OBJECTIVE: To describe the clinicopathological characteristics of the MS
      Lesion Project biopsy cohort. METHODS: Clinical characteristics and disability of
      patients with pathologically confirmed inflammatory demyelinating disease
      (excluding ADEM) classified immunopathologically (n = 91) and patients from the
      Olmsted County MS prevalence cohort (n = 218) were determined. RESULTS: Most
      patients who underwent biopsy and had pathologically proved demyelinating disease
      ultimately developed definite (n = 70) or probable (n = 12) MS (median follow up
      4.4 years). Most had a relapsing remitting course and 73% were ambulatory (EDSS <
      or =4) at last follow up. Nine patients remained classified as having an isolated
      demyelinating syndrome at last follow up. Patients with different
      immunopathological patterns had similar clinical characteristics. Although
      presenting symptoms and sex ratios differed, the clinical course in biopsy
      patients was similar to the prevalence cohort. Median EDSS was <4.0 in both
      cohorts when matched for disease duration, sex, and age. CONCLUSIONS: Most
      patients undergoing biopsy, who had pathologically confirmed demyelinating
      disease, were likely to develop MS and remain ambulatory after a median disease
      duration of 4.4 years. The immunopathological patterns lacked specific clinical
      correlations and were not related to the timing of the biopsy. These data suggest
      that pathogenic implications derived largely from MS biopsy studies may be
      extrapolated to the general MS population.

PMID- 16291897
TI  - Antinuclear antibodies define a subgroup of paraneoplastic neuropathies: clinical
      and immunological data.
AB  - OBJECTIVE: Paraneoplastic neuropathy is a clinical and immunological
      heterogeneous disorder and attempts have been made to classify subgroups of this
      disease. Only 30-50% of the clinical defined cases have antineuronal antibodies.
      METHODS: The clinical and immunological features of 36 patients with
      paraneoplastic neuropathy from the authors' database were analysed including the
      type and course of the neuropathy, associated tumours, and the presence of
      antineuronal and other autoantibodies. RESULTS: Antineuronal antibodies were
      detected in 17/36 patients (47%) and anti-Hu was the most frequent antineuronal
      antibody. Nine patients had high titre antinuclear antibodies (ANA, median titre
      1/1000) without antineuronal antibodies. ANA reactivities were different in most
      patients. Comparison of the ANA positive and ANA negative patients revealed that
      ANA positive paraneoplastic neuropathy is more frequently associated with breast
      cancer but is not associated with lung cancer (p<0.05). The main clinical type in
      these patients was sensorimotor neuropathy. No ANA positive patient had central
      nervous system involvement. Although the Rankin score at the time of diagnosis
      was not different, the functional outcome in ANA positive patients was better
      than in ANA negative patients (p<0.05). CONCLUSIONS: Paraneoplastic neuropathy is
      a heterogeneous disorder. ANA may define a subgroup of paraneoplastic neuropathy
      with different clinical and immunological features and may be related to better
      prognosis of the neuropathic symptoms.

PMID- 16291899
TI  - Vis attractiva and vis nervosa.

PMID- 16291898
TI  - Validation of a short disease specific quality of life scale for hemifacial
      spasm: correlation with SF-36.
AB  - BACKGROUND: A short, practical, and validated quality of life (QoL) scale for
      hemifacial spasm (HFS) is not currently available. OBJECTIVES: To examine the
      reliability and validity of a short self-rating scale (HFS-7) by comparing HFS
      patients with healthy controls. We also evaluated the correlation of HFS-7 with
      the physical and mental domains of SF-36, a generic QoL scale. METHODS: Seven
      self-rating items (HFS-7) were administered to HFS patients and healthy controls.
      In addition, HFS patients answered the SF-36 questionnaire. The validity and
      reliability of HFS-7 were analysed and correlation between HFS-7 and SF-36
      examined. RESULTS: A total of 178 subjects were enrolled in the study, including
      85 HFS patients with mean age of 54.8 (SD 11.0) years, of whom 52 (61.2%) were
      women, and 93 controls with mean age of 51.4 (SD 10.0) years, of whom 59 (63.4%)
      were women. The test-retest intraclass correlation coefficient for the seven
      items was between 0.75 and 0.90 and Cronbach's coefficient of reliability for the
      HFS-7 scale was 0.88. Every item in HFS-7 discriminated between disease and
      controls (p<0.0001). The HFS-7 summary index correlated with the SF-36 summary
      score (Spearman's correlation r = -0.28, p = 0.009), in particular the mental
      health summary score (r = -0.416, p<0.0001) and the emotional domain (r = -0.466,
      p<0.00001). CONCLUSION: HFS-7 could prove useful as a simple clinical tool to
      assess and monitor QoL measures in HFS patients.

PMID- 16291900
TI  - Pallidal stimulation in dystonia: effects on cognition, mood, and quality of
      life.
AB  - Bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi)
      alleviates symptoms in patients with dystonia but its effects on cognition,
      neuropsychiatric status, and quality of life have not been examined. This is a
      case series report of 15 consecutive patients with different forms of dystonia
      who underwent bilateral implantation of DBS electrodes in the GPi. The patients
      were evaluated preoperatively and after 3-12 months of DBS with tests of
      cognition (Mattis Dementia Rating Scale, Stroop Test, Trail Making Test, Phonemic
      and Category Word Fluency, Digit Span, Rey Auditory Verbal Learning Test, Tonic
      and Phasic Alertness), neuropsychiatric status (Beck Depression and Anxiety
      Inventories, Montgomery Asberg Depression Rating Scale, Snaith-Hamilton Pleasure
      Scale, Brief Psychiatric Rating Scale), quality of life, and motor functions. GPi
      DBS significantly improved dystonic symptoms, functional abilities, and quality
      of life allowing for a significant reduction of antidystonic medications. No
      deterioration was observed in cognitive scores and neuropsychiatric measures. The
      present case series report thus provides preliminary evidence for the safety of
      GPi DBS regarding cognitive and neuropsychiatric functions in patients with
      dystonia.

PMID- 16291901
TI  - Acanthocytosis as a predisposing factor for non-ketotic hyperglycaemia induced
      chorea-ballism.
AB  - BACKGROUND: Episodic non-ketotic hyperglycaemia in patients with diabetes may be
      responsible for a syndrome characterised by hemichorea-hemiballism associated
      with unique radiological features. OBJECTIVE: To investigate whether factors
      other than hyperglycaemia may be responsible for the neurological involvement.
      METHODS: Three patients who developed a persistent chorea-ballism syndrome
      triggered by a hyperglycaemic crisis were investigated. In these patients, the
      persistence of the involuntary movements required neuroleptic medication.
      RESULTS: T1 weighted magnetic resonance imaging revealed bilateral hyperintense
      lesions involving the striatum. Surprisingly, in these patients, the laboratory
      investigations revealed peripheral red blood cell acanthocytosis in a significant
      proportion of cells. CONCLUSION: Compared with the large population of patients
      with diabetes who do not show abnormal involuntary movements, unrecognised
      acanthocytosis in diabetes might render patients prone to develop hemichorea
      hemiballism.

PMID- 16291902
TI  - Spinocerebellar ataxia type 14: study of a family with an exon 5 mutation in the
      PRKCG gene.
AB  - We report our observations in an Australian family with spinocerebellar ataxia
      type 14 (SCA 14). We describe a novel mutation in exon 5 of the PRKCG gene,
      altering a highly conserved cysteine to a phenylalanine at codon 150, and record
      the detailed clinical observations in six affected family members.

PMID- 16291903
TI  - Balo's concentric sclerosis associated with primary human herpesvirus 6
      infection.
AB  - BACKGROUND: Balo's concentric sclerosis (BCS) is a demyelinating disorder
      believed to be a rare variant of multiple sclerosis (MS). Human herpesvirus 6
      (HHV-6) is a highly neurotropic virus causing severe central nervous system (CNS)
      infections predominantly following reactivation of latent HHV-6 in
      immunocompromised individuals. Primary infection with HHV-6 usually occurs in
      early childhood manifesting as exanthema subitum. The clinical spectrum of
      primary infection in adolescents or adults has not yet been evaluated. CASE
      REPORT: A previously healthy 13 year old girl developed acute hemianopsia and
      anomia 5 days after an episode of fever and malaise of unknown origin. Cerebral
      MRI revealed three white matter lesions, one with ring-like contrast enhancement.
      Lumbar puncture showed mononuclear pleocytosis of 30 cells/microl, oligoclonal
      IgG, and a normal protein level. Follow up cerebral MRI scans revealed lamellar
      concentric hemispheric lesions characteristic of BCS. The first neurological
      symptoms of the patient coincided with primary HHV-6 CNS infection, diagnosed by
      a positive PCR test of the CSF together with seroconversion. Response to
      antiviral and corticosteroid treatment was only temporary, but immunoglobulin
      treatment has so far been followed by clinical stability for 30 months.
      CONCLUSIONS: To our knowledge, this is the first report both of an association
      between HHV-6 and BCS and of immunoglobulin treatment of BCS. A late primary
      infection with HHV-6 might be associated with BCS. Further studies in patients
      with this rare disease are needed to confirm this association and to evaluate the
      efficacy of antiviral and immunoglobulin treatment.

PMID- 16291904
TI  - Unidirectional whole body turning: a new lateralising sign in complex partial
      seizures.
AB  - BACKGROUND: The lateralising significance of unidirectional whole body turning in
      patients with complex partial seizures (CPS) arising from the temporal lobe was
      evaluated. METHODS: A total of 330 patients undergoing long term video-EEG study
      were included. "Unidirectional whole body turning" was defined as rotation of the
      trunk, head, and limbs by >90 degrees and lasting >10 s. EEG correlates, MRI, and
      SPECT findings were compared and outcome after surgery was noted for patients
      with follow up data for >1 year. RESULTS: Unidirectional whole body turning was
      observed in 13 patients with a mean age of 18+/-8 years. Concordance of the side
      of whole body turning with the EEG focus and MRI findings was observed in 11 of
      the 13 patients (84.7%) and in 26 of 28 seizures (92.8%). The six patients who
      underwent temporal lobectomy or resection of lesion, opposite to the direction of
      body turning, had good seizure outcome. CONCLUSION: Unidirectional whole body
      turning is a new lateralising sign in temporal lobe CPS with good predictive
      value for epileptogenic focus contralateral to the direction of turning.

PMID- 16291905
TI  - Lamotrigine reduces migraine aura and migraine attacks in patients with migraine
      with aura.
AB  - This study examined the efficacy of lamotrigine in the prevention of migraine
      aura. Fifty nine patients suffering from migraine with aura received lamotrigine
      in a controlled three year prospective open study. Treatment response was defined
      as a reduction of aura frequency each month by at least 50%. Primary endpoint was
      reached by three quarters of the patients. Lamotrigine significantly reduced both
      frequency of migraine aura (mean, 1.5 (SD, 0.6) each month before v 0.4 (0.7)
      after treatment; p < 0.001) and aura duration (mean, 27 (SD, 11) minutes before v
      8 (14) after treatment; p < 0.001). Furthermore, more than three quarters of
      those patients with a reduction of aura symptoms experienced a significant
      reduction of frequency of migraine attacks (mean, 2.1 (SD, 1.0) each month before
      v 1.2 (1.1) after treatment; p < 0.001). Lamotrigine was highly effective in
      reducing migraine aura and migraine attacks. The strong correlation between
      reduction of aura symptoms and migraine attacks stresses the potential role of
      aura-like events and possibly cortical spreading depression as a trigger for
      trigeminal vascular activation, and subsequently the development of migraine
      headaches.

PMID- 16291906
TI  - Efficacy of TNF {alpha} blockade in cyclophosphamide resistant neuro-Behcet
      disease.
AB  - Behcet disease is a chronic relapsing inflammatory condition, predominantly
      affecting young adults, characterised by recurrent bipolar aphtae and systemic
      manifestations for which tumour necrosis factor (TNF) alpha blockade has recently
      emerged as an effective treatment. We report the case of a patient presenting
      with mucocutaneous and ocular manifestations who in the course of his disease
      developed CNS parenchymal involvement. While being treated with pulsed
      cyclophosphamide and corticosteroids, he suffered a relapse of his CNS
      involvement that was efficaciously controlled by infliximab. No disease activity
      was observed during a full year of TNF blockade, associated with azathioprine,
      colchicine, and corticosteroids. However, 7 months after the last administration
      of infliximab and still under immunosuppressant agents, CNS lesions recurred.
      Infliximab was successfully reintroduced and since continued with no side
      effects. The sequence of events observed in this patient suggests that TNF
      blockade is efficacious in suppressing neuro-Behcet disease and once introduced
      should be maintained for a prolonged period of time.

PMID- 16291908
TI  - Neurological Picture. Ultra fast resolution of acute post-traumatic subdural
      haematoma.

PMID- 16291907
TI  - Ambiguous value of Haemophilus influenzae isolation in Guillain-Barre and Fisher
      syndromes.
AB  - BACKGROUND: Haemophilus influenzae is considered a causative agent of Guillain
      Barre syndrome (GBS) and Fisher syndrome, but the frequency of this infection in
      GBS is controversial. OBJECTIVE: To determine whether isolation of H influenzae
      indicates it is a causative agent in GBS and Fisher syndrome. RESULTS: Four (15%)
      of 27 patients with GBS and Fisher syndrome in whom H influenzae was isolated
      were also seropositive for Campylobacter jejuni. Antiganglioside IgG antibodies
      in these four patients did not cross react with their H influenzae lipo
      oligosaccharides, whereas antiganglioside antibodies in the four patients with
      positive serology for H influenzae did. CONCLUSIONS: The findings suggest that H
      influenzae isolation is not always indicative of the causative agent in these
      syndromes and that tests for other infections should be made, even in cases of
      positive culture.

PMID- 16291909
TI  - "Who came with you?" A diagnostic observation in patients with memory problems?

PMID- 16291910
TI  - Disseminated Pseudallescheria boydii infection successfully treated with
      voriconazole.

PMID- 16291912
TI  - Video assessment of rTMS for Tourette syndrome.

PMID- 16291911
TI  - Ocular tilt reaction and anterior inferior cerebellar artery syndrome.

PMID- 16291913
TI  - A case of superior cerebellar artery syndrome with contralateral hearing loss at
      onset.

PMID- 16291916
TI  - Neurology in practice: the final supplement--dementia.

PMID- 16291917
TI  - The clinical assessment of the patient with early dementia.

PMID- 16291918
TI  - Epidemiology and risk factors of dementia.

PMID- 16291919
TI  - Apraxia, agnosias, and higher visual function abnormalities.

PMID- 16291920
TI  - Vascular cognitive impairment.

PMID- 16291921
TI  - Use of laboratory and imaging investigations in dementia.

PMID- 16291922
TI  - Treatment of dementia.

PMID- 16291923
TI  - Neuropathological investigation of dementia: a guide for neurologists.

PMID- 16291924
TI  - Funding priorities in animal reproduction at the United States Department of
      Agriculture's Cooperative State Research, Education, and Extension Service.
AB  - The National Research Initiative (NRI) Competitive Grants Program is the U.S.
      Department of Agriculture's major competitive grants program and is administered
      by the Cooperative State Research, Education, and Extension Service (CSREES).
      Since its inception in 1991, the NRI has funded competitive grants in the
      discipline of animal reproduction. Previously, this program provided funding for
      a broad range of projects encompassing almost every subdiscipline in reproductive
      biology of farm animals, including aquatic species important to the aquaculture
      industry. During fiscal year 2004, the NRI Animal Reproduction Program narrowed
      the focus of funding priorities to the topics of infertility, basic mechanisms
      regulating fertility, cryopreservation of gametes, reducing the postpartum
      interval to conception, and sterilization methods or development of monosex
      populations. In response to a directive to further narrow the focus of funding
      priorities for fiscal year 2005 and beyond, CSREES conducted a Stakeholder
      Workshop on Funding Priorities in Animal Reproduction at the 37th Annual Meeting
      of the Society for the Study of Reproduction in Vancouver, Canada. More than 75
      stakeholder scientists from a cross section of federal, public, and private
      institutions from across the United States participated in the workshop and
      provided recommendations to CSREES for future NRI-funding priorities in Animal
      Reproduction. The recommendations provided by stakeholders included continuing
      efforts to focus funding priorities into fewer high-impact areas relevant to
      animal agriculture and aquaculture. Recommendations also included movement back
      toward subdisciplines of animal reproduction that cut across all applicable
      species. The three funding priorities that consistently emerged as
      recommendations from the workshop participants were 1) gonadal function and
      production of gametes, 2) pituitary-hypothalamic function, and 3) embryo and
      conceptus development, including interaction between the conceptus and uterus.
      These funding priorities were considered when preparing the fiscal year 2006 NRI
      Request for Applications.

PMID- 16291925
TI  - Signaling pathways for modulation of mouse sperm motility by adenosine and
      catecholamine agonists.
AB  - Capacitation of mammalian sperm, including alterations in flagellar motility, is
      presumably modulated by chemical signals encountered in the female reproductive
      tract. This work investigates signaling pathways for adenosine and catecholamine
      agonists that stimulate sperm kinetic activity. We show that 2-chloro-2'
      deoxyadenosine and isoproterenol robustly accelerate flagellar beat frequency
      with EC50s near 10 and 0.05 microM, respectively. The several-fold acceleration
      is maximal by 60 sec. Although extracellular Ca2+ is required for agonist action
      on the flagellar beat, agonist treatment does not elevate sperm cytosolic [Ca2+]
      but does increase cAMP content. Acceleration does not require the conventional
      transmembrane adenylyl cyclase ADCY3, since it persists in sperm of ADCY3
      knockout mice and in wild-type sperm in the presence of the inhibitors of
      conventional adenylyl cyclases SQ-22536, MDL-12330A, or 2', 5'-dideoxyadenosine.
      In contrast, the acceleration by these agents is absent in sperm that lack the
      predominant atypical adenylyl cyclase, SACY. Responses to these agonists are also
      absent in sperm from mice lacking the sperm-specific Calpha2 catalytic subunit of
      protein kinase A (PRKACA). Agonist responses also are strongly suppressed in wild
      type sperm by the protein kinase inhibitor H-89. These results show that
      adenosine and catecholamine analogs activate sperm motility by mechanisms that
      require extracellular Ca2+, the atypical sperm adenylyl cyclase, cAMP, and
      protein kinase A.

PMID- 16291926
TI  - Sperm mobility: deduction of a model explaining phenotypic variation in roosters
      (Gallus domesticus).
AB  - In previous work, variation in sperm mobility phenotype was attributed to the
      proportion of ejaculated fowl sperm containing dysfunctional mitochondria. In the
      present work, latent mitochondrial dysfunction was inferred from patterns of
      sperm egress from the oviduct's sperm-storage tubules. In addition, experiments
      were performed to help explain how mitochondrial function could be compromised in
      viable sperm cells. Confocal microscopy demonstrated that sperm Ca2+ content
      differed between low and high sperm-mobility phenotypes when sperm were stained
      with rhod-2 AM, a Ca2+ -specific dye. Fluorescence was associated with the
      nuclear envelope, a variant of the endoplasmic reticulum, and greater
      fluorescence was observed in sperm from low sperm-mobility males. Fluorescence
      was reduced by 50% when motile sperm were rendered immotile by incubation with a
      Ca2+ chelator. Thus, a relationship was established between a dynamic
      intracellular Ca2+ pool and sperm motility. Sperm N-methy-D-aspartic acid (NMDA)
      receptors were inferred by the action of D-homocysteinesulfinic acid, a potent
      NMDA receptor agonist. Seminal plasma from low sperm mobility males was
      characterized by an elevated glutamate concentration. Thapsigargin, which
      inhibits the smooth endoplasmic reticulum Ca2+ pump and thereby promotes Ca2+
      efflux, rendered sperm immotile. This effect was blocked by cyclosporin A, which
      prevents the formation of the mitochondrial permeability transition pore (PTP) in
      response to elevated mitochondrial Ca2+ content. In summary, we propose that 1)
      glutamate enables Ca2+ uptake into sperm before ejaculation, 2) excessive Ca2+
      uptake triggers formation of the PTP in a subpopulation of sperm, and 3) sperm
      mobility is decreased in proportion.

PMID- 16291927
TI  - Gene expression of cox5a, 5b, or 6b1 and their roles in preimplantation mouse
      embryos.
AB  - To investigate the role of nuclear encoded genes in mitochondrial function during
      oocyte maturation and early embryogenesis we examined the expression pattern and
      function of the cytochrome oxidase (Cox) subunits, Cox5a, 5b, and 6b1 during
      oocyte maturation and early embryo development. Transcription of Cox5a, 5b, or
      6b1 was observed in oocytes and during early development; their expression levels
      were abundant in mature oocytes (MII) and zygotes (1C), and lowest at the 2-cell
      stage (2C), gradually increasing from 4-cell to blastocyst stage.
      Immunocytochemical studies revealed that COX5A, 5B, or 6B1 proteins were
      expressed in all blastomeres of the blastocyst. Silencing of mRNA expression by
      RNA interference (siRNA) did not inhibit oocyte maturation or developmental
      events up to the morula and blastocyst stages, but disrupted mitochondrial
      distribution. Significantly higher apoptosis and lower cell numbers were observed
      in siRNA-treated blastocysts. Real time RT-PCR revealed that silencing of Cox5a,
      5b, or 6b1 did not alter mRNA levels of Bcl-xL (Bcl2l1), but increased
      transcription levels of proapoptotic genes, Bax and caspase 3 (Casp3).
      Furthermore, mRNA and protein levels of E-cadherin (CDH1) were decreased in siRNA
      microinjected blastocysts. These results suggest that gene expression of the Cox
      subunits, Cox5a, 5b, and 6b1 is not required for embryo developmental events up
      to the blastocyst stage. The loss of these genes leads to mitochondrial
      dysfunction that results in apoptosis of the blastocyst stage embryos.

PMID- 16291928
TI  - Leisure activity and risk of cognitive impairment: the Chongqing aging study.
AB  - The authors followed 5,437 people aged 55 years and older with normal baseline
      Mini-Mental State Examination score annually for 5 years. The mean incidence of
      cognitive impairment was 2.3% per year. Cognitive activities in both the
      individual item (playing board games and reading) and the composite measure were
      associated with the reduced risk of cognitive impairment, while watching
      television was associated with an increased risk of cognitive impairment.

PMID- 16291929
TI  - Rapid disease progression correlates with instability of mutant SOD1 in familial
      ALS.
AB  - Studies on the clinical course of familial ALS suggest that the duration of
      illness is relatively consistent for each mutation but variable among the
      different mutations. The authors analyzed the relative amount of mutant compared
      with normal SOD1 protein in the erythrocytes from 29 patients with ALS with 22
      different mutations. Turnover of mutant SOD1 correlated with a shorter disease
      survival time.

PMID- 16291931
TI  - Do we know what the early visual system does?
AB  - We can claim that we know what the visual system does once we can predict neural
      responses to arbitrary stimuli, including those seen in nature. In the early
      visual system, models based on one or more linear receptive fields hold promise
      to achieve this goal as long as the models include nonlinear mechanisms that
      control responsiveness, based on stimulus context and history, and take into
      account the nonlinearity of spike generation. These linear and nonlinear
      mechanisms might be the only essential determinants of the response, or
      alternatively, there may be additional fundamental determinants yet to be
      identified. Research is progressing with the goals of defining a single "standard
      model" for each stage of the visual pathway and testing the predictive power of
      these models on the responses to movies of natural scenes. These predictive
      models represent, at a given stage of the visual pathway, a compact description
      of visual computation. They would be an invaluable guide for understanding the
      underlying biophysical and anatomical mechanisms and relating neural responses to
      visual perception.

PMID- 16291932
TI  - Binding of the positron emission tomography tracer Pittsburgh compound-B reflects
      the amount of amyloid-beta in Alzheimer's disease brain but not in transgenic
      mouse brain.
AB  - During the development of in vivo amyloid imaging agents, an effort was made to
      use micro-positron emission tomography (PET) imaging in the presenilin-1
      (PS1)/amyloid precursor protein (APP) transgenic mouse model of CNS amyloid
      deposition to screen new compounds and further study Pittsburgh Compound-B (PIB),
      a PET tracer that has been shown to be retained well in amyloid-containing areas
      of Alzheimer's disease (AD) brain. Unexpectedly, we saw no significant retention
      of PIB in this model even at 12 months of age when amyloid deposition in the
      PS1/APP mouse typically exceeds that seen in AD. This study describes a series of
      ex vivo and postmortem in vitro studies designed to explain this low retention.
      Ex vivo brain pharmacokinetic studies confirmed the low in vivo PIB retention
      observed in micro-PET experiments. In vitro binding studies showed that PS1/APP
      brain tissue contained less than one high-affinity (K(d) = 1-2 nm) PIB binding
      site per 1000 molecules of amyloid-beta (Abeta), whereas AD brain contained >500
      PIB binding sites per 1000 molecules of Abeta. Synthetic Abeta closely resembled
      PS1/APP brain in having less than one high-affinity PIB binding site per 1000
      molecules of Abeta, although the characteristics of the few high-affinity PIB
      binding sites found on synthetic Abeta were very similar to those found in AD
      brain. We hypothesize that differences in the time course of deposition or tissue
      factors present during deposition lead to differences in secondary structure
      between Abeta deposited in AD brain and either synthetic Abeta or Abeta deposited
      in PS1/APP brain.

PMID- 16291933
TI  - Serotoninergic modulation of chloride homeostasis during maturation of the
      locomotor network in zebrafish.
AB  - During development, neural networks progress through important functional changes
      such as the generation of spontaneous activity, the expression of a depolarizing
      chloride gradient, and the appearance of neuromodulation. Little is known about
      how these processes are integrated to yield mature behaviors. We showed
      previously that, during the maturation of the locomotor network of the zebrafish,
      endogenous serotonin (5HT) increased motor activity by reducing intervals of
      inactivity, without affecting the active swim periods that are the target of 5HT
      in other and more mature preparations. Because membrane properties were constant
      during the rest intervals, we examined here whether 5HT modulates chloride
      homeostasis. We compared the effects of blocking (inward) chloride cotransport
      with bumetanide to the effects of 5HT and its antagonists, both behaviorally by
      video imaging and cellularly by whole-cell and gramicidin-perforated patch
      recordings. Bumetanide mimicked the effects of 5HT antagonists, by prolonging
      rest intervals without affecting the properties of swim episodes (duration;
      frequency; extent of depolarization) either behaviorally or during fictive
      swimming. Furthermore, bumetanide and 5HT antagonists suppressed the amplitude of
      depolarizing responses evoked by ionophoresis of glycine onto spinal neurons in
      the presence of tetrodotoxin and transiently suppressed the amplitude of
      responses to glycine measured after fictive swimming. The effects of bumetanide
      contrasted with and occluded the effects of 5HT. We suggest that, during
      development, endogenous 5HT modulates chloride homeostasis during the quiescent
      intervals and thereby offsets the long periods of quiescence commonly observed in
      developing networks to allow expression of sustained and behaviorally relevant
      activity.

PMID- 16291934
TI  - Identification of molluscan nicotinic acetylcholine receptor (nAChR) subunits
      involved in formation of cation- and anion-selective nAChRs.
AB  - Acetylcholine (ACh) is a neurotransmitter commonly found in all animal species.
      It was shown to mediate fast excitatory and inhibitory neurotransmission in the
      molluscan CNS. Since early intracellular recordings, it was shown that the
      receptors mediating these currents belong to the family of neuronal nicotinic
      acetylcholine receptors and that they can be distinguished on the basis of their
      pharmacology. We previously identified 12 Lymnaea cDNAs that were predicted to
      encode ion channel subunits of the family of the neuronal nicotinic acetylcholine
      receptors. These Lymnaea nAChRs can be subdivided in groups according to the
      residues supposedly contributing to the selectivity of ion conductance.
      Functional analysis in Xenopus oocytes revealed that two types of subunits with
      predicted distinct ion selectivities form homopentameric nicotinic ACh receptor
      (nAChR) subtypes conducting either cations or anions. Phylogenetic analysis of
      the nAChR gene sequences suggests that molluscan anionic nAChRs probably evolved
      from cationic ancestors through amino acid substitutions in the ion channel pore,
      a mechanism different from acetylcholine-gated channels in other invertebrates.

PMID- 16291935
TI  - Rac1 induces the clustering of AMPA receptors during spinogenesis.
AB  - Glutamatergic synapses switch from nonspiny synapses to become dendritic spines
      during early neuronal development. Here, we report that the lack of sufficient
      Rac1, a small RhoGTPase, contributes to the absence of spinogenesis in immature
      neurons. The overexpression of green fluorescence protein-tagged wild-type Rac1
      initiated the formation of dendritic spines in cultured dissociated hippocampal
      neurons younger than 11 d in vitro, indicating that Rac1 is likely one of the
      missing pieces responsible for the lack of spines in immature neurons. The
      overexpression of wild-type Rac1 also induced the clustering of AMPA receptors
      (AMPARs) and increased the amplitude of miniature EPSCs (mEPSCs). The expression
      of constitutively active Rac1 induced the formation of unusually large synapses
      with large amounts of AMPAR clusters. Also, our live imaging experiments revealed
      that the contact of an axon induced the clustering of Rac1, and subsequent
      morphological changes led to spinogenesis. Additionally, the overexpression of
      wild-type Rac1 and constitutively active Rac1 increased the size of preexisting
      spines and the amplitude of mEPSCs in mature neurons (>21 d in vitro) within 24 h
      after transfection. Together, these results indicate that activation of Rac1
      enhances excitatory synaptic transmission by recruiting AMPARs to synapses during
      spinogenesis, thus providing a mechanistic link between presynaptic and
      postsynaptic developmental changes. Furthermore, we show that Rac1 has two
      distinct roles at different stages of neuronal development. The activation of
      Rac1 initiates spinogenesis at an early stage and regulates the function and
      morphology of preexisting spines at a later stage.

PMID- 16291936
TI  - Age-dependent neurofibrillary tangle formation, neuron loss, and memory
      impairment in a mouse model of human tauopathy (P301L).
AB  - Here, we describe the generation of a novel transgenic mouse model of human
      tauopathy. The rTg(tau(P301L))4510 mouse expresses the P301L mutation in tau
      (4R0N) associated with frontotemporal dementia and parkinsonism linked to
      chromosome 17. Transgene expression was driven by a forebrain-specific Ca(2+)
      calmodulin kinase II promoter system resulting in high levels of expression in
      the hippocampus and neocortex. Importantly, transgene expression in this model is
      induced via the tetracycline-operon responsive element and is suppressed after
      treatment with doxycycline. Continued transgene expression in rTg(tau(P301L))4510
      mice results in age-dependent development of many salient characteristics of
      hereditary human dementia. From an early age, immunohistochemical studies
      demonstrated abnormal biochemical processing of tau and the presence of
      pathological conformation- and phosphorylation-dependent epitopes.
      Neurofibrillary tangle (NFT) pathology was first observed in the neocortex and
      progressed into the hippocampus and limbic structures with increasing age.
      Consistent with the formation of NFTs, immunoblots indicated an age-dependent
      transition of accumulating tau species from Sarkosyl soluble 55 kDa to insoluble
      hyperphosphorylated 64 kDa. Ultrastructural analysis revealed the presence of
      straight tau filaments. Furthermore, the effects of tau(P301L) expression on
      spatial reference memory were longitudinally tested using the Morris water maze.
      Compared with nontransgenic age-matched control littermates, rTg(tau(P301L))4510
      mice developed significant cognitive impairments from 4 months of age. Memory
      deficits were accompanied by gross forebrain atrophy and a prominent loss of
      neurons, most strikingly in hippocampal subdivision CA1. Collectively, these data
      describe a novel transgenic mouse that closely mimics human tauopathy and may
      represent an important model for the future study of tau-related
      neurodegenerative disease.

PMID- 16291937
TI  - Interaural phase and level difference sensitivity in low-frequency neurons in the
      lateral superior olive.
AB  - The lateral superior olive (LSO) is believed to encode differences in sound level
      at the two ears, a cue for azimuthal sound location. Most high-frequency
      sensitive LSO neurons are binaural, receiving inputs from both ears. An
      inhibitory input from the contralateral ear, via the medial nucleus of the
      trapezoid body (MNTB), and excitatory input from the ipsilateral ear enable level
      differences to be encoded. However, the classical descriptions of low-frequency
      sensitive neurons report primarily monaural cells with no contralateral
      inhibition. Anatomical and physiological evidence, however, shows that low
      frequency LSO neurons receive low-frequency inhibitory input from ipsilateral
      MNTB, which in turn receives excitatory input from the contralateral cochlear
      nucleus and low-frequency excitatory input from the ipsilateral cochlear nucleus.
      Therefore, these neurons would be expected to be binaural with contralateral
      inhibition. Here, we re-examined binaural interaction in low-frequency (less than
      approximately 3 kHz) LSO neurons and phase locking in the MNTB. Phase locking to
      low-frequency tones in MNTB and ipsilaterally driven LSO neurons with frequency
      sensitivities <1.2 kHz was enhanced relative to the auditory nerve. Moreover,
      most low-frequency LSO neurons exhibited contralateral inhibition: ipsilaterally
      driven responses were suppressed by raising the level of the contralateral
      stimulus; most neurons were sensitive to interaural time delays in pure tone and
      noise stimuli such that inhibition was nearly maximal when the stimuli were
      presented to the ears in-phase. The data demonstrate that low-frequency LSO
      neurons of cat are not monaural and can exhibit contralateral inhibition like
      their high-frequency counterparts.

PMID- 16291938
TI  - Effect of domain interaction on apolipoprotein E levels in mouse brain.
AB  - Apolipoprotein (apo) E4 is a risk factor for heart disease, Alzheimer's disease,
      and other forms of neurodegeneration, but the underlying mechanisms are unknown.
      Domain interaction, a structural property that distinguishes apoE4 from apoE2 and
      apoE3, results in more rapid turnover and lower plasma levels of apoE4. To
      determine whether domain interaction affects brain apoE levels, we analyzed brain
      homogenates from human apoE3 and apoE4 knock-in mice, wild-type mice, and Arg-61
      apoE mice, in which domain interaction was introduced by gene targeting. As
      determined on Western blots, the hemibrain, cortex, hippocampus, and cerebellum
      of knock-in mice had 30-40% lower levels of apoE4 than apoE3, and Arg-61 mice had
      25-50% lower apoE levels than wild-type mice. In the CSF, Arg-61 apoE level was
      40% lower than the wild-type level. Arg-61 apoE mRNA levels were similar to or
      slightly higher than wild-type apoE mRNA levels. Thus, the lower Arg-61 apoE
      levels were not attributable to decreased mRNA levels. In culture medium from
      heterozygous Arg-61/wild-type and apoE4/apoE3 primary astrocytes, Arg-61 apoE and
      apoE4 levels were lower than wild-type apoE and apoE3, respectively, suggesting
      that primary astrocytes secrete lower amounts of Arg-61 apoE and apoE4. These
      results demonstrate that domain interaction is responsible for the lower levels
      of both human apoE4 and mouse Arg-61 apoE in mouse brain. Cells may recognize
      apoE4 and Arg-61 apoE as misfolded proteins and target them for degradation or
      accumulation. Thus, degradation/accumulation or lower levels of apoE4 may
      contribute to the association of apoE4 with Alzheimer's disease.

PMID- 16291939
TI  - Mitogen-activated protein kinase-mediated reinforcement of hippocampal early long
      term depression by the type IV-specific phosphodiesterase inhibitor rolipram and
      its effect on synaptic tagging.
AB  - Rolipram, a selective inhibitor of cAMP-specific phosphodiesterase 4 (PDE4), has
      been shown to reinforce an early form of long-term potentiation (LTP) to a long
      lasting LTP (late LTP). Furthermore, it was shown that the effects of rolipram
      mediated reinforcement of LTP interacts with processes of synaptic tagging
      (Navakkode et al., 2004). Here we show in CA1 hippocampal slices from adult rats
      in vitro that rolipram also converted an early form of long-term depression (LTD)
      that normally decays within 2-3 h, to a long-lasting LTD (late LTD) if rolipram
      was applied during LTD-induction. Rolipram-reinforced LTD (RLTD) was NMDA
      receptor- and protein synthesis-dependent. Furthermore, it was dependent on the
      synergistic coactivation of dopaminergic D(1) and D(5) receptors. This let us
      speculate that RLTD resembles electrically induced, conventional CA1 late LTD,
      which is characterized by heterosynaptic processes and synaptic tagging. We
      therefore asked whether synaptic tagging occurs during RLTD. We found that early
      LTD in an S1 synaptic input was transformed into late LTD if early LTD was
      induced in a second independent S2 synaptic pathway during the inhibition of PDE
      by rolipram, supporting the interaction of processes of synaptic tagging during
      RLTD. Furthermore, application of PD 98059 (2'-amino-3'-methoxyflavone) or U0126
      (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene), specific
      inhibitors of mitogen-activated protein kinases (MAPKs), prevented RLTD,
      suggesting a pivotal role of MAPK activation for RLTD. This MAPK activation was
      triggered during RLTD by the synergistic interaction of NMDA receptor- and D(1)
      and D(5) receptor-mediated Rap/B-Raf pathways, but not by the Ras/Raf-1 pathway
      in adult hippocampal CA1 neurons, as shown by the use of the pathway-specific
      inhibitors manumycin (Ras/Raf-1) and lethal toxin 82 (Rap/B-Raf).

PMID- 16291940
TI  - The G-protein-coupled serotonin receptor SER-1 regulates egg laying and male
      mating behaviors in Caenorhabditis elegans.
AB  - Serotonin (5-HT) is a neuromodulator that regulates many aspects of animal
      behavior, including mood, aggression, sex drive, and sleep. In vertebrates, most
      of the behavioral effects of 5-HT appear to be mediated by G-protein-coupled
      receptors (GPCRs). Here, we show that SER-1 is the 5-HT GPCR responsible for the
      stimulatory effects of exogenous 5-HT in two sexually dimorphic behaviors of
      Caenorhabditis elegans, egg laying and male ventral tail curling. Loss of ser-1
      function leads to decreased egg laying in hermaphrodites and defects in the
      turning step of mating behavior in males. ser-1 is expressed in muscles that are
      postsynaptic to serotonergic neurons and are known to be required for these
      behaviors. Analysis of the ser-1 mutant also reveals an inhibitory effect of 5-HT
      on egg laying that is normally masked by SER-1-dependent stimulation. This
      inhibition of egg laying requires MOD-1, a 5-HT-gated chloride channel. Loss of
      mod-1 function in males also produces defects in ventral tail curling and
      enhances the turning defects in ser-1 mutant males. Sustained elevations in 5-HT
      levels result in behavioral adaptation to both the stimulatory and inhibitory
      actions of the neurotransmitter, indicating that both SER-1 and MOD-1 signaling
      can be modulated. Removal of wild-type animals from high levels of exogenous 5-HT
      produces a SER-1-dependent withdrawal response in which egg laying is
      significantly decreased. These studies provide insight into the role of 5-HT in
      behavior and the regulation of 5-HT(2) receptor function.

PMID- 16291941
TI  - Evidence for a significant role of alpha 3-containing GABAA receptors in
      mediating the anxiolytic effects of benzodiazepines.
AB  - The GABA(A) receptor subtypes responsible for the anxiolytic effects of
      nonselective benzodiazepines (BZs) such as chlordiazepoxide (CDP) and diazepam
      remain controversial. Hence, molecular genetic data suggest that alpha2-rather
      than alpha3-containing GABA(A) receptors are responsible for the anxiolytic
      effects of diazepam, whereas the anxiogenic effects of an alpha3-selective
      inverse agonist suggest that an agonist selective for this subtype should be
      anxiolytic. We have extended this latter pharmacological approach to identify a
      compound, 4,2'-difluoro-5'-[8-fluoro-7-(1-hydroxy-1-methylethyl)imidazo[1,2
      a]pyridin-3-yl]biphenyl-2-carbonitrile (TP003), that is an alpha3 subtype
      selective agonist that produced a robust anxiolytic-like effect in both rodent
      and non-human primate behavioral models of anxiety. Moreover, in mice containing
      a point mutation that renders alpha2-containing receptors BZ insensitive
      (alpha2H101R mice), TP003 as well as the nonselective agonist CDP retained
      efficacy in a stress-induced hyperthermia model. Together, these data show that
      potentiation of alpha3-containing GABA(A) receptors is sufficient to produce the
      anxiolytic effects of BZs and that alpha2 potentiation may not be necessary.

PMID- 16291943
TI  - Lamina propria and olfactory bulb ensheathing cells exhibit differential
      integration and migration and promote differential axon sprouting in the lesioned
      spinal cord.
AB  - Olfactory bulb-derived (central) ensheathing cell (OB OEC) transplants have shown
      significant promise in rat models of spinal cord injury, prompting the use of
      lamina propria-derived (peripheral) olfactory ensheathing cells (LP OECs) in both
      experimental and clinical trials. Although derived from a common embryonic
      precursor, both sources of OECs reside in different nervous system compartments
      postnatally, and their ability to promote regeneration and efficacy after
      transplantation may differ depending on both their source and mode of
      transplantation. Here, we have purified green fluorescent protein-expressing LP
      and OB OECs, assayed their biological differences in vitro, and transplanted them
      acutely either directly into or rostral and caudal to a dorsolateral funiculus
      crush. LP and OB OECs exhibit multiple morphological and antigenic similarities
      in vitro, and, after transplantation, they both attenuate lesion and cavity
      formation and promote angiogenesis, endogenous Schwann cell infiltration, and
      axonal sprouting. However, an increased mitotic rate and migratory ability of LP
      OECs in vitro was reflected in vivo by their superior ability to migrate within
      the spinal cord, reduce cavity formation and lesion size, and differentially
      stimulate outgrowth of axonal subpopulations compared with OB OECs. An undesired
      behavior (autotomy) was also significantly enhanced by LP OEC, over OB OEC,
      transplantation. These results suggest that LP and OB OECs exhibit intrinsic
      biological differences that, after transplantation into the lesioned CNS, result
      in differences in postlesion spinal cord neuropathology and anatomical and
      behavioral regeneration outcomes that also vary depending on direct versus
      rostrocaudal transplantation.

PMID- 16291942
TI  - Neurological and neurodegenerative alterations in a transgenic mouse model
      expressing human alpha-synuclein under oligodendrocyte promoter: implications for
      multiple system atrophy.
AB  - Multiple system atrophy (MSA) is a progressive, neurodegenerative disease
      characterized by parkinsonism, ataxia, autonomic dysfunction, and accumulation of
      alpha-synuclein (alpha-syn) in oligodendrocytes. To better understand the
      mechanisms of neurodegeneration and the role of alpha-syn accumulation in
      oligodendrocytes in the pathogenesis of MSA, we generated transgenic mouse lines
      expressing human (h) alpha-syn under the control of the murine myelin basic
      protein promoter. Transgenic mice expressing high levels of halpha-syn displayed
      severe neurological alterations and died prematurely at 6 months of age.
      Furthermore, mice developed progressive accumulation of halpha-syn-immunoreactive
      inclusions in oligodendrocytes along the axonal tracts in the brainstem, basal
      ganglia, cerebellum, corpus callosum, and neocortex. The inclusions also reacted
      with antibodies against phospho-serine (129) halpha-syn and ubiquitin, and halpha
      syn was found in the detergent-insoluble fraction. In high-expresser lines, the
      white matter tracts displayed intense astrogliosis, myelin pallor, and decreased
      neurofilament immunostaining. Accumulation of halpha-syn in oligodendrocytes also
      leads to prominent neurodegenerative changes in the neocortex with decreased
      dendritic density and to loss of dopaminergic fibers in the basal ganglia. The
      oligodendrocytic inclusions were composed of fibrils and accompanied by
      mitochondrial alterations and disruption of the myelin lamina in the axons.
      Together, these studies support the contention that accumulation of alpha-syn in
      oligodendrocytes promotes neurodegeneration and recapitulates several of the key
      functional and neuropathological features of MSA.

PMID- 16291944
TI  - Stable ensemble performance with single-neuron variability during reaching
      movements in primates.
AB  - Significant variability in firing properties of individual neurons was observed
      while two monkeys, chronically implanted with multielectrode arrays in frontal
      and parietal cortical areas, performed a continuous arm movement task. Although
      the degree of correlation between the firing of single neurons and movement
      parameters was nonstationary, stable predictions of arm movements could be
      obtained from the activity of neuronal ensembles. This result adds support to the
      idea that movement parameters are redundantly encoded in the motor cortex, such
      that brain networks can achieve the same behavioral goals through different
      patterns and relative contribution of individual neuron activity. This has
      important implications for neural prosthetics, suggesting that accurate operation
      of a brain-machine interface requires recording from large neuronal ensembles to
      minimize the effect of variability and ensuring stable performance over long
      periods of time.

PMID- 16291945
TI  - Critical role of calcitonin gene-related peptide 1 receptors in the amygdala in
      synaptic plasticity and pain behavior.
AB  - The role of neuropeptides in synaptic plasticity is less well understood than
      that of classical transmitters such as glutamate. Here we report the importance
      of the G-protein-coupled calcitonin gene-related peptide (CGRP1) receptor as a
      critical link between amygdala plasticity and pain behavior. A key player in
      emotionality and affective disorders, the amygdala has been implicated in the
      well documented, but mechanistically unexplained, relationship between pain and
      affect. Our electrophysiological and pharmacological in vitro (patch-clamp
      recordings) and in vivo (extracellular single-unit recordings) data show that
      selective CGRP1 receptor antagonists (CGRP(8-37) and BIBN4096BS) in the amygdala
      reverse arthritis pain-related plasticity through a protein kinase A (PKA)
      dependent postsynaptic mechanism that involves NMDA receptors. CGRP1 receptor
      antagonists inhibited synaptic plasticity in the laterocapsular division of the
      central nucleus of the amygdala (CeLC) in brain slices from arthritic rats
      compared with normal controls. The effects were accompanied by decreased neuronal
      excitability and reduced amplitude, but not frequency, of miniature EPSCs; paired
      pulse facilitation was unaffected. The antagonist effects were occluded by a PKA
      inhibitor. CGRP1 receptor blockade also directly inhibited NMDA-evoked, but not
      AMPA-evoked, membrane currents. Together, these data suggest a postsynaptic site
      of action. At the systems level, the antagonists reversed the sensitization of
      nociceptive CeLC neurons in anesthetized rats in the arthritis pain model.
      Importantly, CGRP1 receptor blockade in the CeLC inhibited spinal (hindlimb
      withdrawal reflexes) and supraspinal pain behavior of awake arthritic rats,
      including affective responses such as ultrasonic vocalizations. This study
      provides direct evidence for the critical dependence of pain behavior on CGRP1
      mediated amygdala plasticity.

PMID- 16291946
TI  - Adult-born and preexisting olfactory granule neurons undergo distinct experience
      dependent modifications of their olfactory responses in vivo.
AB  - Neurogenesis continues throughout adulthood in the mammalian olfactory bulb and
      hippocampal dentate gyrus, suggesting the hypothesis that recently generated,
      adult-born neurons contribute to neural plasticity and learning. To explore this
      hypothesis, we examined whether olfactory experience modifies the responses of
      adult-born neurons to odorants, using immediate early genes (IEGs) to assay the
      response of olfactory granule neurons. We find that, shortly after they
      differentiate and synaptically integrate, the population of adult-born olfactory
      granule neurons has a greater population IEG response to novel odors than mature,
      preexisting neurons. Familiarizing mice with test odors increases the response of
      the recently incorporated adult-born neuron population to the test odors, and
      this increased responsiveness is long lasting, demonstrating that the response of
      the adult-born neuron population is altered by experience. In contrast,
      familiarizing mice with test odors decreases the IEG response of developmentally
      generated neurons, suggesting that recently generated adult-born neurons play a
      distinct role in olfactory processing. The increased IEG response is stimulus
      specific; familiarizing mice with a set of different, "distractor" odors does not
      increase the adult-born neuron population response to the test odors. Odor
      familiarization does not influence the survival of adult-born neurons, indicating
      that the changes in the population response of adult-born neurons are not
      attributable to increased survival of odor-stimulated neurons. These results
      demonstrate that recently generated adult-born olfactory granule neurons and
      older, preexisting granule neurons undergo contrasting experience-dependent
      modifications in vivo and support the hypothesis that adult-born neurons are
      involved in olfactory learning.

PMID- 16291947
TI  - Post-training lesions of the medial prefrontal cortex interfere with subsequent
      performance of trace eyeblink conditioning.
AB  - Rabbits were trained on trace eyeblink (EB) conditioning until they reached a
      criterion of 10 consecutive EB conditioned responses (CRs). Electrolytic lesions
      were made in the medial prefrontal cortex (mPFC) centered on the prelimbic area
      (Brodmann's area 32), at five different intervals after training. These included
      immediately, 24 h, 1 and 2 weeks, and 1 month after training. Separate groups of
      animals received sham lesions at these same intervals after training. After a 2
      week postoperative recovery period, all animals were retested for 3 d on trace
      conditioning, using the same parameters used during preoperative training. Mean
      EB conditioning performance deficits occurred in the animals with mPFC lesions
      compared with sham-lesioned animals on the first day of retesting in all five
      groups. However, by the second or third day of retesting, the rabbits with
      lesions were performing at a level that was comparable with that of sham animals.
      Rabbits that received more posterolateral lesions of the neocortex did not,
      however, show postoperative conditioning deficits. A comparison of percentage EB
      CRs of animals with postoperative training with that of animals that received
      mPFC lesions before training suggests that the mPFC post-training lesions produce
      damage to a retrieval process and not to a storage site or an acquisition
      process.

PMID- 16291948
TI  - CCAAT/enhancer-binding protein phosphorylation biases cortical precursors to
      generate neurons rather than astrocytes in vivo.
AB  - The intracellular mechanisms that bias mammalian neural precursors to generate
      neurons versus glial cells are not well understood. We demonstrated previously
      that the growth factor-regulated mitogen-activated protein kinase kinase (MEK)
      and its downstream target, the CCAAT/enhancer-binding protein (C/EBP) family of
      transcription factors, are essential for neurogenesis in cultured cortical
      precursor cells (Menard et al., 2002). Here, we examined a role for this pathway
      during cortical cell fate determination in vivo using in utero electroporation of
      the embryonic cortex. These studies demonstrate that inhibition of the activity
      of either MEK or the C/EBPs inhibits the genesis of neurons in vivo. Moreover,
      the MEK pathway mediates phosphorylation of C/EBPbeta in cortical precursors, and
      expression of a C/EBPbeta construct in which the MEK pathway phosphorylation
      sites are mutated inhibits neurogenesis. Conversely, expression of a C/EBPbeta
      construct, in which the same sites are mutated to glutamate and therefore are
      "constitutively" phosphorylated, enhances neurogenesis in the early embryonic
      cortex. A subpopulation of precursors in which C/EBP activity is inhibited are
      maintained as cycling precursors in the ventricular/subventricular zone of the
      cortex until early in postnatal life, when they have an enhanced propensity to
      generate astrocytes, presumably in response to gliogenic signals in the neonatal
      environment. Thus, activation of an MEK-C/EBP pathway in cortical precursors in
      vivo biases them to become neurons and against becoming astrocytes, thereby
      acting as a growth factor-regulated switch.

PMID- 16291949
TI  - Sexually dimorphic synaptic organization of the medial amygdala.
AB  - The medial amygdala is important in social behaviors, many of which differ
      between males and females. The posterodorsal subnucleus of the medial amygdala
      (MeApd) is particularly sensitive to gonadal steroid hormones and is a likely
      site for gonadal hormone regulation of sexually dimorphic social behavior. Here
      we show that the synaptic organization of the MeApd in the rat is sexually
      dimorphic and lateralized before puberty. With the use of whole-cell voltage
      clamp recording and quantitative electron microscopy, we found that, specifically
      in the left hemisphere, prepubertal males have approximately 80% more excitatory
      synapses per MeApd neuron than females. In the left but not the right MeApd,
      miniature EPSC (mEPSC) frequency was significantly greater in males than in
      females; mEPSC amplitude was not sexually dimorphic. Paired-pulse facilitation of
      EPSCs, an index of release probability, also was not sexually dimorphic,
      suggesting that greater mEPSC frequency is caused by a difference in excitatory
      synapse number. Electron microscopy confirmed that the asymmetric synapse-to
      neuron ratio and the total asymmetric synapse number were significantly greater
      in the left MeApd of males than of females. In contrast to results for excitatory
      synapses, we found no evidence of sexual dimorphism or laterality in inhibitory
      synapses. Neither the frequency nor the amplitude of mIPSCs was sexually
      dimorphic or lateralized. Likewise, the number of symmetric synapses measured
      with electron microscopy was not sexually dimorphic. These findings show that the
      excitatory synaptic organization of the left MeApd is sexually differentiated
      before puberty, which could provide a sexually dimorphic neural substrate for the
      effects of hormones on adult social behavior.

PMID- 16291950
TI  - A role for protein phosphatases 1, 2A, and 2B in cerebellar long-term
      potentiation.
AB  - Cerebellar parallel fiber (PF)-Purkinje cell (PC) synapses can undergo
      postsynaptically expressed long-term depression (LTD) or long-term potentiation
      (LTP). PF-LTD induction requires the coactivity of the PF and CF (climbing fiber)
      inputs to PCs and a concomitant calcium transient and activation of protein
      kinase C (PKC). PF-LTP can be induced by PF activity alone and requires a lower
      calcium transient for its induction than PF-LTD. The cellular events triggering
      PF-LTP induction are not well characterized. At other types of synapses (e.g., in
      the hippocampus), bidirectional synaptic plasticity is under control of a
      kinase/phosphatase switch, with PKC and CaMKII (calcium/calmodulin-dependent
      kinase II) activity promoting LTP induction and phosphatase activity promoting
      LTD induction. Here, we have tested for the involvement of protein phosphatase 1
      (PP1), PP2A, and PP2B (calcineurin) in cerebellar LTP induction using whole-cell
      patch-clamp recordings in rat cerebellar slices. LTP induction was blocked in the
      presence of the PP1/2A inhibitors okadaic acid and microcystin LR, the PP1
      inhibitory peptide inhibitor-2, the PP2A inhibitor fostriecin, and the PP2B
      inhibitor cyclosporin A. LTP induction was not impaired by the PKC inhibitor
      chelerythrine. Conversely, LTD induction was not blocked by microcystin LR but
      instead was reduced when active PP2B was injected into PCs. These data indicate
      that a kinase/phosphatase switch controls bidirectional cerebellar plasticity,
      but in a manner "inverse" to the dependencies found at other types of synapses.
      Therefore, cerebellar LTP constitutes the only form of LTP described so far that
      depends on phosphatase rather than kinase activity.

PMID- 16291951
TI  - PBK/TOPK, a proliferating neural progenitor-specific mitogen-activated protein
      kinase kinase.
AB  - We performed genomic subtraction coupled to microarray-based gene expression
      profiling and identified the PDZ (postsynaptic density-95/Discs large/zona
      occludens-1)-binding kinase/T-LAK (lymphokine-activated killer T cell) cell
      originating protein kinase (PBK/TOPK) as a gene highly enriched in neural stem
      cell cultures. Previous studies have identified PBK/TOPK as a mitogen-activated
      protein kinase (MAPK) kinase that phosphorylated P38 MAPK but with no known
      expression or function in the nervous system. First, using a novel,
      bioinformatics-based approach to assess cross-correlation in large microarray
      datasets, we generated the hypothesis of a cell-cycle-related role for PBK/TOPK
      in neural cells. We then demonstrated that both PBK/TOPK and P38 are activated in
      a cell-cycle-dependent manner in neuronal progenitor cells in vitro, and
      inhibition of this pathway disrupts progenitor proliferation and self-renewal, a
      core feature of progenitors. In vivo, PBK/TOPK is expressed in rapidly
      proliferating cells in the adult subependymal zone (SEZ) and early postnatal
      cerebellar external granular layer. Using an approach based on transgenically
      targeted ablation and lineage tracing in mice, we show that PBK/TOPK-positive
      cells in the SEZ are GFAP negative but arise from GFAP-positive neural stem cells
      during adult neurogenesis. Furthermore, ablation of the adult stem cell
      population leads to concomitant loss of PBK/TOPK-positive cells in the SEZ.
      Together, these studies demonstrate that PBK/TOPK is a marker for transiently
      amplifying neural progenitors in the SEZ. Additionally, they suggest that
      PBK/TOPK plays an important role in these progenitors, and further implicates the
      P38 MAPK pathway in general, as an important regulator of progenitor
      proliferation and self-renewal.

PMID- 16291952
TI  - Signal propagation and logic gating in networks of integrate-and-fire neurons.
AB  - Transmission of signals within the brain is essential for cognitive function, but
      it is not clear how neural circuits support reliable and accurate signal
      propagation over a sufficiently large dynamic range. Two modes of propagation
      have been studied: synfire chains, in which synchronous activity travels through
      feedforward layers of a neuronal network, and the propagation of fluctuations in
      firing rate across these layers. In both cases, a sufficient amount of noise,
      which was added to previous models from an external source, had to be included to
      support stable propagation. Sparse, randomly connected networks of spiking model
      neurons can generate chaotic patterns of activity. We investigate whether this
      activity, which is a more realistic noise source, is sufficient to allow for
      signal transmission. We find that, for rate-coded signals but not for synfire
      chains, such networks support robust and accurate signal reproduction through up
      to six layers if appropriate adjustments are made in synaptic strengths. We
      investigate the factors affecting transmission and show that multiple signals can
      propagate simultaneously along different pathways. Using this feature, we show
      how different types of logic gates can arise within the architecture of the
      random network through the strengthening of specific synapses.

PMID- 16291954
TI  - Gap junctions modulate interkinetic nuclear movement in retinal progenitor cells.
AB  - During early retinal development, progenitor cells must divide repeatedly to
      expand the progenitor pool. During G(1) and G(2) of the cell cycle, progenitor
      cell nuclei migrate back-and-forth across the proliferative zone in a process
      termed interkinetic nuclear movement. Because division can only occur at the
      ventricular surface, factors that affect the speed of nuclear movement could
      modulate the duration of the cell cycle. Gap-junctional coupling and gap junction
      dependent Ca(2+) activity are common features of proliferating cells in the
      immature nervous system. Furthermore, both gap-junctional coupling and changes in
      [Ca(2+)](i) have been shown to be positively correlated with the migration of a
      number of immature cell types. Using time-lapse confocal microscopy, we describe
      the nature and rate of progenitor cell interkinetic nuclear movement. We show
      that nuclear movement is usually, but not always, associated with Ca(2+)
      transients and that buffering of these transients with BAPTA slows movement.
      Furthermore, we show for the first time that gap-junctional communication is an
      important requirement for the maintenance of normal nuclear movement in retinal
      progenitor cells. Conventional blockers of gap junctions and transfection of
      cells with dominant-negative constructs of connexin 43 (Cx43) and Cx43-specific
      antisense oligodeoxynucleotides (asODNs) all act to slow interkinetic nuclear
      movement. The gap junction mimetic peptide Gap26 also acts to slow movement, an
      effect that we show may be attributable to the blockade of gap junction
      hemichannels.

PMID- 16291953
TI  - Neural correlates of fine depth discrimination in monkey inferior temporal
      cortex.
AB  - Binocular disparity is an important visual cue that gives rise to the perception
      of depth. Disparity signals are widely spread across the visual cortex, but their
      relative role is poorly understood. Here, we addressed the correlation between
      the responses of disparity-selective neurons in the occipitotemporal (ventral)
      visual pathway and the behavioral discrimination of stereoscopic depth. We
      recorded activity of disparity-selective neurons in the inferior temporal cortex
      (IT) while monkeys were engaged in a fine stereoscopic depth discrimination
      (stereoacuity) task. We found that trial-to-trial fluctuations in neuronal
      responses correlated with the monkey's perceptual choice. We suggest that
      disparity signals in the IT, located in the ventral visual pathway, are
      functionally linked to the discrimination of fine-grain depth.

PMID- 16291956
TI  - Why haven't we heard the sky is falling?

PMID- 16291955
TI  - Prevention of oxidative stress injury to sperm.

PMID- 16291957
TI  - Microfluidic applications for andrology.

PMID- 16291958
TI  - Use of electroejaculation in the presence of anal stenosis.

PMID- 16291959
TI  - Specialty spotlight: urology.

PMID- 16291960
TI  - Synopsis: XVIIIth Testis Workshop, "Testicular Cell Dynamics and Endocrine
      Signaling".

PMID- 16291961
TI  - Synopsis: 2005 annual meeting of the American Society of Andrology.

PMID- 16291962
TI  - Memorial Geoff Malcolm Hasting Waites (1928-2005).

PMID- 16291963
TI  - Increase in testicular temperature and vascularization induced by hypobaric
      hypoxia in rats.
AB  - The exposure of male rats to continuous chronic hypobaric hypoxia (HH) and
      intermittent chronic hypobaric hypoxia induced evident changes in testicular
      morphology and spermatogenic cell metabolism. The mechanisms that underlie these
      changes under HH are not known. In this work, we have tested the hypothesis that
      in rats subjected to HH, the testis undergoes changes in vascularization leading
      to changes in temperature homeostasis. Male Wistar rats (247 +/- 16 g) were
      maintained in normobaric or hypobaric (428 torr, equivalent to 4600 m a.s.l)
      conditions. At days 0, 5, 15, and 30 postexposure, 12 rats were anesthetized with
      ketamine, and the intratesticular temperature was determined. These rats were
      subsequently sacrificed and the testicles were fixed in formaldehyde and
      processed for routine histological analysis. Our results showed that the height
      of the seminiferous epithelium decreased significantly at day 5 posthypoxia and
      thereafter, indicating a decreased spermatogenesis. Intratesticular temperature
      increased (1.5 degrees C) and remained high after 5 days of hypoxia exposure.
      Correlated with these changes, histometrical analysis of the number of blood
      vessels in the testicular interstitium was significantly increased by day 5 and
      afterwards. Morphological classification of interstitial blood vessels indicates
      a transition from capillaries to larger vessels as the hypoxia exposure
      progresses.

PMID- 16291965
TI  - Tungstate treatment improves Leydig cell function in streptozotocin-diabetic
      rats.
AB  - Oral administration of sodium tungstate to adult male streptozotocin-diabetic
      rats for 3 months normalized serum levels of glucose, insulin, luteinizing
      hormone, and follicle-stimulating hormone. These effects were accompanied by an
      increase in reproductive performance, which was related to a strong improvement
      in Leydig cell function markers, such as the recovery of the number of Leydig
      cells and serum testosterone levels. Moreover, this in vivo recovery was related
      to a concomitant increase in the cell expression of insulin receptors. Tungstate
      treatment did not modify Leydig cell function in healthy rats. Furthermore, the
      addition of tungstate or insulin to the mTLC-1 cell line from Leydig cell origin
      increased the phosphorylation states of MAP-kinase and glycogen synthase kinase
      3. Our results indicate that tungstate treatment in diabetic rats leads to a
      recovery of reproductive performance by increasing the number of Leydig cells.
      This increase contributes to the recovery of their functionality, thereby
      improving the overall function of these cells. We propose that this improvement
      is caused by the combined effect of the tungstate-induced normalization of
      insulin glucose and luteinizing hormone serum levels and a direct action of the
      effector on Leydig cells through modulation of at least MAP-kinase and glycogen
      synthase kinase-3 activities.

PMID- 16291964
TI  - Depletion of endogenous germ cells in male pigs and goats in preparation for germ
      cell transplantation.
AB  - The efficiency of germ cell transplantation, the procedure of transferring germ
      cells from a donor male into the testes of recipient males, can be greatly
      increased by reduction of endogenous germ cells in recipient animals. To develop
      effective methods for suppression of endogenous spermatogenesis in potential pig
      and goat recipients, we either administered busulfan to pregnant sows or
      irradiated the testes of immature goats. Piglets from sows treated twice with
      busulfan (7.5 mg/kg) at days 98 and 108 of gestation showed reduced gonocyte
      numbers at 2, 4, and 8 weeks of age and reduced initiation of spermatogenesis at
      16 weeks of age. For goats, groups of 3 kids at 1, 5, or 9.5 weeks of age
      received fractionated irradiation of the testes with 3 doses of 2 Gy on 3
      consecutive days. At 2 months after irradiation, 5%-10% of seminiferous tubule
      cross sections contained pachytene spermatocytes, compared with 50%-100% in
      controls. At 3 months after irradiation, spermatozoa appeared in 20% of tubule
      cross sections in all treated goats and in 100% of tubules in control goats. By 6
      months after irradiation, spermatogenesis had recovered in 60% of tubules in
      goats treated at 5 or 9.5 weeks of age but in only 29% of tubules after treatment
      at 1 week of age. Therefore, late gestation in utero treatment of pigs with low
      doses of busulfan and testicular irradiation of goats at 1 week of age will
      result in a reduction in the endogenous germ cell population that could
      facilitate donor cell colonization after germ cell transplantation.

PMID- 16291966
TI  - Identification of sperm morphometric subpopulations in two different portions of
      the boar ejaculate and its relation to postthaw quality.
AB  - A statistical approach using sequentially principal component analysis (PCA),
      clustering, and discriminant analyses was developed to identify sperm
      morphometric subpopulations in well-defined portions of the fresh boar ejaculate.
      Semen was obtained as 2 portions (the first 10 mL of the sperm-rich fraction and
      the rest of the ejaculate, respectively) and frozen using a conventional
      protocol. Before freezing, an aliquot was used for computer-assisted sperm
      morphometry analysis (ASMA). Postthaw quality was evaluated using computer
      assisted sperm analysis (CASA), and an annexin-V/PI assay evaluated sperm
      membranes. The PCA revealed that 3 variables represented more than 78% of the
      cumulative variance in sperm subpopulations. The clustering and discriminant
      analyses, based on 5780 individual spermatozoa, revealed the existence of 4 sperm
      subpopulations. The relative percentage of these subpopulations varied between
      boar and ejaculate portions. Linear regression models based on measured
      morphometric characteristics could account for up to 36% of the percentage of
      intact sperm membranes postthaw. The ASMA protocol used in our study was useful
      to detect subtle morphometric differences between spermatozoa, and the
      combination of this analysis with a multivariate statistical procedure gave new
      information on the biological characteristics of boar ejaculates that is not
      given by conventional sperm analysis.

PMID- 16291967
TI  - Trisialoganglioside GT1b prevents increase in sperm membrane molecular ordering
      induced by in vitro lipid peroxidation.
AB  - The effect of various types of gangliosides, the sialic acid-containing
      glycosphingolipids, on human sperm membrane during lipid peroxidation induced by
      Fe(2+)/ascorbate ions was investigated. The monosialoganglioside (GM1),
      disialogangliosides (GD1a and GD1b), and trisialoganglioside (GT1b) were examined
      at a concentration of 100 microM, which was above their respective critical
      micellar concentrations. Lipid peroxidation was determined by quantification of
      malondialdehyde (MDA) concentration. The molecular orientational order in the
      membrane was assessed by fluorescence spectroscopy and electron paramagnetic
      resonance spectroscopy. Both approaches revealed a significant increase in
      membrane rigidity following oxidation, which correlated with an increase in the
      MDA level. The preincubation of spermatozoa with GM1 and GD1a did not have any
      effect on induced lipid peroxidation. In the presence of GD1b and GT1b, a reduced
      formation of MDA and a decrease in membrane rigidity was detected. The inhibitory
      effect of GT1b micelles toward membrane oxidation damage was found to be greater
      than that of GD1b. In conclusion, a direct relationship between the reduced
      content of the accumulated MDA and the longer preservation of the native-like
      membrane molecular ordering during sperm oxidation in the presence of GT1b
      suggests its protective effect. This phenomenon could be due to the specific GT1b
      conformation and its negative surface potential.

PMID- 16291969
TI  - DNA integrity is compromised in protamine-deficient human sperm.
AB  - The objective of this study was to examine the relationship between DNA integrity
      and protamines in human sperm. One hundred forty-nine male infertility patients
      were included in an Institutional Review Board-approved study. Sperm were
      evaluated for DNA fragmentation using the DNA Integrity Assay, a test equivalent
      to the sperm chromatin structure assay (SCSA). Additionally, nuclear proteins
      were extracted and the protamine-1/protamine-2 ratio (P1/P2), protamine-1 (P1),
      protamine-2 (P2), and total protamine concentrations were evaluated. We
      identified 37 patients with abnormally low P1/P2 ratios, 99 patients with normal
      P1/P2 ratios, and 13 patients with abnormally high P1/P2 ratios. DNA
      fragmentation was significantly elevated in patients with low P1/P2 ratios (37.1
      +/- 6.02) vs those with normal and high P1/P2 ratios (26.7 +/- 1.9 and 23.8 +/-
      3.2, respectively; P < .05) and was inversely correlated with the P1/P2 ratio
      (R(s) -0.18, P < .05), P1 concentration (R(s) -0.29, P < .001), P2 concentration
      (R(s) - 0.24, P < .005), and total protamine concentration (R(s) -0.28, P <
      .001). Furthermore, chi2 analysis revealed a significant increase in the
      incidence of marked DNA fragmentation in patients with diminished levels of
      either P1 or P2. The present study is the first to report that human sperm
      protamine content is significantly related to DNA fragmentation. In particular,
      sperm P1 and P2 concentrations inversely correlate with DNA fragmentation,
      indicating a protective role of the protamines against sperm DNA damage. In light
      of recent studies highlighting the negative effect of sperm DNA damage on ART
      outcomes, these findings indicate a possible clinical significance for human
      sperm protamine levels.

PMID- 16291968
TI  - A cyclic adenosine 3',5'-monophosphate stimulates phospholipase Cgamma1-calcium
      signaling via the activation of tyrosine kinase in boar spermatozoa.
AB  - The aim of this study was to reveal a downstream part of the intracellular
      signaling that is mediated by cyclic adenosine monophosphate (cAMP)-dependent
      tyrosine kinases, including spleen tyrosine (Y) kinase (SYK), in boar
      spermatozoa. Ejaculated spermatozoa were incubated with cBiMPS (a cell-permeable
      cAMP analog; 0.1 mM) at 38.5 degrees C for 180 minutes and then used for Western
      blot and indirect immunofluorescence. Incubation of spermatozoa with cBiMPS
      induced tyrosine phosphorylation at the linker region of SYK (which was essential
      to binding to phospholipase C [PLC]gamma1) in the connecting and principal
      pieces, but the tyrosine phosphorylation was abolished by the addition of H-89 (a
      protein kinase A [PKA] inhibitor; 0.01-0.1 mM). Moreover, the cAMP-dependent
      tyrosine phosphorylation was also induced at the key regulatory residue of
      PLCgamma1 in the same segments of spermatozoa, but it was inhibited by the
      addition of herbimycin A (a tyrosine kinase inhibitor; 5 microM). These results
      suggest that the sperm cAMP-dependent tyrosine kinases, including SYK, are linked
      to the activation of PLCgamma1. Indirect immunofluorescence clearly detected both
      inositol 1,4,5-trisphosphate (IP(3)) receptor and calreticulin in the connecting
      piece, indicating the presence of internal calcium store. Cell imaging with fluo
      3/AM (a cell-permeable Ca(2+) indicator) showed that incubation of spermatozoa
      with cBiMPS increased intracellular free calcium in the middle piece, but that it
      was reduced by the addition of U-73122 (a PLC inhibitor; 0.02 mM). Based on our
      findings, we conclude that the connecting piece of boar spermatozoa possesses the
      PLCgamma1-IP(3) receptor-calcium signaling that is triggered by cAMP and mediated
      by PKA and herbimycin A-sensitive tyrosine kinases, including SYK.

PMID- 16291970
TI  - Supplementation of the thawing media with reduced glutathione improves function
      and the in vitro fertilizing ability of boar spermatozoa after cryopreservation.
AB  - In this study, we evaluated the effects of glutathione (L-g-glutamyl-L
      cysteinylglycine; GSH) supplementation of the thawing extender on semen
      parameters to compensate for the decrease in GSH content observed during sperm
      freezing. To fully address these questions, we used a set of functional sperm
      tests. These included tests of motility and motion parameters, changes in
      sulfhydryl group content in membrane proteins, capacitation status, measures of
      intra-cellular reactive oxygen species generation, sperm chromatin condensation,
      and in vitro penetration of immature oocytes. The main findings emerging from
      this study were that addition of GSH to the thawing media resulted in a lower
      number of capacitated viable spermatozoa, a decrease in the number of spermatozoa
      with changes in the sulfhydryl groups in membrane proteins, a reduction of the
      reactive oxygen species generation, a lower chromatin condensation, and a higher
      penetration ability of oocytes in vitro and a higher proportion of decondensated
      sperm heads. GSH appears to play an important role in sperm antioxidant defense
      strategy. Addition of GSH to the thawing extender could be of significant benefit
      in improving the function and fertilizing capacity of frozen boar spermatozoa.

PMID- 16291971
TI  - Combination therapy: medicated urethral system for erection enhances sexual
      satisfaction in sildenafil citrate failure following nerve-sparing radical
      prostatectomy.
AB  - The objective of our study was to assess the effectiveness of combining medicated
      urethral system for erection (MUSE) with sildenafil citrate in men unsatisfied
      with the sildenafil alone. Baseline and follow-up data from 23 patients (mean
      age, 62.5 +/- 5.23 years) unsatisfied with the use of the sildenafil citrate
      alone for the treatment of erectile dysfunction following nerve-sparing radical
      prostatectomy (mean use, 4 attempts/100-mg dose) was obtained. All patients
      started oral sildenafil citrate more than 6 months after radical prostatectomy.
      Combination therapy was initiated using 100 mg sildenafil citrate orally 1 hour
      prior to intercourse. Patients used combination therapy for a minimum of 4
      attempts prior to assessment with the Sexual Health Inventory of Men
      (International Index for Erectile Function-5) and visual analog scale to gauge
      rigidity (0-100). The effect of therapy on the total International Index for
      Erectile Function (IIEF) score and penile rigidity score was assessed. Of the 23
      patients, 4 (17%) had no improvement with the addition of medicated urethral
      system for erection and discontinued the drug, while 19 (83%) reported
      improvement with the penile rigidity and sexual satisfaction. The IIEF scores of
      these 19 patients showed significant improvements in each sexual domain, and the
      patients reported that erection was sufficient for vaginal penetration 80% of the
      time. Rigidity scores on a scale of 0-100 with sildenafil alone averaged 38% (23
      53) for men and 46% (26-67) for their partners. With the addition of MUSE, scores
      increased to 76% for men and 62% for their partners. We conclude that the
      addition of MUSE to sildenafil improved sexual satisfaction and penile rigidity
      in patients unsatisfied with sildenafil alone.

PMID- 16291972
TI  - Monoclonal antibody from vasectomized mouse identifies a conserved testis
      specific antigen TSA70.
AB  - Vasectomy results in the occlusion of testicular outflow, leading to autoimmunity
      characterized by the production of antisperm antibodies (ASA). Reports on the
      rise in ASA following vasectomy in several species are available; however, not
      much is known about the specific sperm autoantigens to which postvasectomy
      antibodies are directed. In the present study, monoclonal antibodies were
      generated using a vasectomized mouse. One of the monoclonal antibodies, D5E5,
      identified an approximately 70-kd antigen localized on the principal piece of the
      tail and also on the tip of the acrosome of mouse sperm. The cognate antigen was
      expressed postmeiotically in a stage-specific manner during spermiogenesis,
      starting from step 8 of elongating spermatids during spermiogenesis up to mature
      spermatozoa. The protein was conserved across the species, as observed by its
      presence in rat, bull, marmoset, and human sperm. Following capacitation, the
      antigen on the head was seen to shift to the acrosomal region and was lost after
      the acrosome reaction. However, the localization on tip of the acrosome still
      persisted, which indicates that the antigen may play a role post-acrosome
      reaction in sperm egg interaction. Resistance to Triton X-100 solubilization
      indicates that TSA70 could be an acrosomal matrix protein. In addition, we
      observed a significant reduction in forward progressive motility of mouse sperm
      treated in vitro with D5E5. In view of its testis specificity, acrosome and tail
      localization, and conserved nature, TSA70 is likely to play an important role in
      sperm function.

PMID- 16291973
TI  - Severe hypospermatogenesis in cases of nonobstructive azoospermia: should we use
      fresh or frozen testicular spermatozoa?
AB  - The aim of this comparative clinical study was to examine whether the fertilizing
      potential of frozen-thawed testicular sperm in the most severe cases of
      hypospermatogenesis is reduced compared with fresh testicular sperm. The results
      could determine the necessity of using fresh testicular sperm cells, which
      mandates involving the spouse by performing simultaneous in vitro fertilization
      intracytoplasmic sperm injection (IVF-ICSI) treatment in this subgroup of
      nonobstructive azoospermia (NOA) patients. We studied 13 couples in which the
      husband was diagnosed as having NOA and few motile testicular sperm cells or only
      immotile testicular sperm cells were isolated by testicular sperm extraction
      (TESE). Each couple underwent both an ICSI cycle, in which fresh testicular sperm
      that were retrieved shortly beforehand were injected, and a consecutive cycle,
      which used frozen-thawed sperm that were retrieved in the original TESE procedure
      but were cryopreserved and stored until use. We found that motility was lost
      during the freezing and thawing process in some cases, which resulted in
      significantly more cycles with only immotile sperm cells for injection in the
      frozen-thawed sperm group (38.5%) than in the fresh sperm group (7.7%; P < .05).
      Availability of only immotile sperm cells significantly reduced fertilization
      rates in both fresh and frozen-thawed groups, but the respective overall
      fertilization rate (44.9% vs 41.1%) and quality of embryos and pregnancy rate
      (18.2% vs 15.4%) were not significantly different between groups. Implantation
      rates were more favorable in the fresh sperm group (10.5% vs 5.9%), but not
      significantly so. We conclude that, although cryopreservation does impair
      motility, which results in significantly more cycles with only immotile sperm
      cells for ICSI in the most severe forms of hypospermatogenesis, fertilization and
      pregnancy rates are not significantly compromised.

PMID- 16291974
TI  - Single-nucleotide polymorphisms and mutation analyses of the TNP1 and TNP2 genes
      of fertile and infertile human male populations.
AB  - Previously, we examined the relationship between protamine gene variations and
      human male infertility. In this study, we show specific variability in the
      transition nuclear protein genes (TNPs) of sterile male patients. Transition
      nuclear proteins (TPs) are major nuclear proteins that replace nuclear histones,
      leading to eventual substitution by protamines during human spermiogenesis.
      Analysis of the human TNP1 and TNP2 gene sequences in 282 sterile male patients
      and 270 (TNP1) and 266 (TNP2) proven-fertile male volunteers revealed 5 amino
      acid substitution-causing single nucleotide polymorphisms (SNPs) in the open
      reading frame of the TNP2 gene. On the other hand, a deletion of 15 nucleotides,
      which encompassed the recognition site for the cAMP response element (CRE)
      transcription factor, was found in the 5'-promoter region of the TNP1 gene in
      infertile men. This deletion reduces TNP1 expression and may cause human male
      infertility.

PMID- 16291975
TI  - Clomiphene administration for cases of nonobstructive azoospermia: a multicenter
      study.
AB  - Clomiphene citrate is a well-established agent that has been empirically used in
      cases of idiopathic oligospermia. Clomiphene increases endogenous gonadotropin
      releasing hormone secretion from the hypothalamus and gonadotropin hormone
      secretion directly from the pituitary and, thus, increases intratesticular
      testosterone concentration. Using intracytoplasmic sperm injection (ICSI), very
      few sperm may be required for fertilization. The objective of this study was to
      determine if the application of clomiphene citrate in males with nonobstructive
      azoospermia might produce sufficient sperm for ICSI, either by resulting in sperm
      identified in the ejaculate or by potentially improving outcomes of surgical
      testicular sperm extraction. Forty-two patients with nonobstructive azoospermia
      (age range, 25-39 years) from 3 international centers were evaluated with routine
      history, physical examination, and hormonal assessment. Initial testicular biopsy
      demonstrated maturation arrest in 42.9% and hypospermatogenesis in 57.1% of
      patients. Clomiphene citrate was administered, with the dose titrated to achieve
      serum testosterone levels between 600 ng/dL and 800 ng/dL, and semen analyses
      were performed at periodic intervals. In patients remaining azoospermic on semen
      analysis, surgical testicular biopsy and sperm extraction were performed. After
      clomiphene citrate therapy, 64.3% of the patients demonstrated sperm in their
      semen analyses ranging from 1 to 16 million sperm/mL, with a mean sperm density
      of 3.8 million/mL. Sufficient sperm for ICSI was retrieved by testicular sperm
      extraction in all patients, even though 35.7% remained azoospermic. Additionally,
      clomiphene citrate administration resulted in a statistically significant
      increase in testis biopsy patterns associated with greater likelihood of sperm
      obtained by surgical extraction (P < .05). We conclude that clomiphene citrate
      administration may result in sperm in the ejaculate of patients with
      nonobstructive azoospermia or the simplification of testis sperm retrieval.
      Surgeons may consider a course of clomiphene citrate administration prior to
      surgical sperm retrieval in patients with nonobstructive azoospermia.

PMID- 16291977
TI  - Image in clinical medicine. Pulmonary sequestration.

PMID- 16291978
TI  - The promise of global cervical-cancer prevention.

PMID- 16291979
TI  - Genetic diversity in melanoma.

PMID- 16291980
TI  - So where's my medal?

PMID- 16291981
TI  - Randomized trial of lifestyle modification and pharmacotherapy for obesity.
AB  - BACKGROUND: Weight-loss medications are recommended as an adjunct to a
      comprehensive program of diet, exercise, and behavior therapy but are typically
      prescribed with minimal or no lifestyle modification. This practice is likely to
      limit therapeutic benefits. METHODS: In this one-year trial, we randomly assigned
      224 obese adults to receive 15 mg of sibutramine per day alone, delivered by a
      primary care provider in eight visits of 10 to 15 minutes each; lifestyle
      modification counseling alone, delivered in 30 group sessions; sibutramine plus
      30 group sessions of lifestyle-modification counseling (i.e., combined therapy);
      or sibutramine plus brief lifestyle-modification counseling delivered by a
      primary care provider in eight visits of 10 to 15 minutes each. All subjects were
      prescribed a diet of 1200 to 1500 kcal per day and the same exercise regimen.
      RESULTS: At one year, subjects who received combined therapy lost a mean (+/-SD)
      of 12.1+/-9.8 kg, whereas those receiving sibutramine alone lost 5.0+/-7.4 kg,
      those treated by lifestyle modification alone lost 6.7+/-7.9 kg, and those
      receiving sibutramine plus brief therapy lost 7.5+/-8.0 kg (P<0.001). Those in
      the combined-therapy group who frequently recorded their food intake lost more
      weight than those who did so infrequently (18.1+/-9.8 kg vs. 7.7+/-7.5 kg,
      P=0.04). CONCLUSIONS: The combination of medication and group lifestyle
      modification resulted in more weight loss than either medication or lifestyle
      modification alone. The results underscore the importance of prescribing weight
      loss medications in combination with, rather than in lieu of, lifestyle
      modification.

PMID- 16291982
TI  - Effects of rimonabant on metabolic risk factors in overweight patients with
      dyslipidemia.
AB  - BACKGROUND: Rimonabant, a selective cannabinoid-1 receptor (CB1) blocker, has
      been shown to reduce body weight and improve cardiovascular risk factors in obese
      patients. The Rimonabant in Obesity-Lipids (RIO-Lipids) study examined the
      effects of rimonabant on metabolic risk factors, including adiponectin levels, in
      high-risk patients who are overweight or obese and have dyslipidemia. METHODS: We
      randomly assigned 1036 overweight or obese patients (body-mass index [the weight
      in kilograms divided by the square of the height in meters], 27 to 40) with
      untreated dyslipidemia (triglyceride levels >1.69 to 7.90 mmol per liter, or a
      ratio of cholesterol to high-density lipoprotein [HDL] cholesterol of >4.5 among
      women and >5 among men) to double-blinded therapy with either placebo or
      rimonabant at a dose of 5 mg or 20 mg daily for 12 months in addition to a
      hypocaloric diet. RESULTS: The rates of completion of the study were 62.6
      percent, 60.3 percent, and 63.9 percent in the placebo group, the group receiving
      5 mg of rimonabant, and the group receiving 20 mg of rimonabant, respectively.
      The most frequent adverse events resulting in discontinuation of the drug were
      depression, anxiety, and nausea. As compared with placebo, rimonabant at a dose
      of 20 mg was associated with a significant (P<0.001) mean weight loss (repeated
      measures method, -6.7+/-0.5 kg, and last-observation-carried-forward analyses, 
      5.4+/-0.4 kg), reduction in waist circumference (repeated-measures method, -5.8+/
      0.5 cm, and last-observation-carried-forward analyses, -4.7+/-0.5 cm), increase
      in HDL cholesterol (repeated-measures method, +10.0+/-1.6 percent, and last
      observation-carried-forward analyses, +8.1+/-1.5 percent), and reduction in
      triglycerides (repeated-measures method, -13.0+/-3.5 percent, and last
      observation-carried-forward analyses, -12.4+/-3.2 percent). Rimonabant at a dose
      of 20 mg also resulted in an increase in plasma adiponectin levels (repeated
      measures method, 57.7 percent, and last-observation-carried-forward analyses,
      46.2 percent; P<0.001), for a change that was partly independent of weight loss
      alone. CONCLUSIONS: Selective CB1-receptor blockade with rimonabant significantly
      reduces body weight and waist circumference and improves the profile of several
      metabolic risk factors in high-risk patients who are overweight or obese and have
      an atherogenic dyslipidemia.

PMID- 16291983
TI  - Distinct sets of genetic alterations in melanoma.
AB  - BACKGROUND: Exposure to ultraviolet light is a major causative factor in
      melanoma, although the relationship between risk and exposure is complex. We
      hypothesized that the clinical heterogeneity is explained by genetically distinct
      types of melanoma with different susceptibility to ultraviolet light. METHODS: We
      compared genome-wide alterations in the number of copies of DNA and mutational
      status of BRAF and N-RAS in 126 melanomas from four groups in which the degree of
      exposure to ultraviolet light differs: 30 melanomas from skin with chronic sun
      induced damage and 40 melanomas from skin without such damage; 36 melanomas from
      palms, soles, and subungual (acral) sites; and 20 mucosal melanomas. RESULTS: We
      found significant differences in the frequencies of regional changes in the
      number of copies of DNA and mutation frequencies in BRAF among the four groups of
      melanomas. Samples could be correctly classified into the four groups with 70
      percent accuracy on the basis of the changes in the number of copies of genomic
      DNA. In two-way comparisons, melanomas arising on skin with signs of chronic sun
      induced damage and skin without such signs could be correctly classified with 84
      percent accuracy. Acral melanoma could be distinguished from mucosal melanoma
      with 89 percent accuracy. Eighty-one percent of melanomas on skin without chronic
      sun-induced damage had mutations in BRAF or N-RAS; the majority of melanomas in
      the other groups had mutations in neither gene. Melanomas with wild-type BRAF or
      N-RAS frequently had increases in the number of copies of the genes for cyclin
      dependent kinase 4 (CDK4) and cyclin D1 (CCND1), downstream components of the RAS
      BRAF pathway. CONCLUSIONS: The genetic alterations identified in melanomas at
      different sites and with different levels of sun exposure indicate that there are
      distinct genetic pathways in the development of melanoma and implicate CDK4 and
      CCND1 as independent oncogenes in melanomas without mutations in BRAF or N-RAS.

PMID- 16291984
TI  - Sildenafil citrate therapy for pulmonary arterial hypertension.
AB  - BACKGROUND: Sildenafil inhibits phosphodiesterase type 5, an enzyme that
      metabolizes cyclic guanosine monophosphate, thereby enhancing the cyclic
      guanosine monophosphate-mediated relaxation and growth inhibition of vascular
      smooth-muscle cells, including those in the lung. METHODS: In this double-blind,
      placebo-controlled study, we randomly assigned 278 patients with symptomatic
      pulmonary arterial hypertension (either idiopathic or associated with connective
      tissue disease or with repaired congenital systemic-to-pulmonary shunts) to
      placebo or sildenafil (20, 40, or 80 mg) orally three times daily for 12 weeks.
      The primary end point was the change from baseline to week 12 in the distance
      walked in six minutes. The change in mean pulmonary-artery pressure and World
      Health Organization (WHO) functional class and the incidence of clinical
      worsening were also assessed, but the study was not powered to assess mortality.
      Patients completing the 12-week randomized study could enter a long-term
      extension study. RESULTS: The distance walked in six minutes increased from
      baseline in all sildenafil groups; the mean placebo-corrected treatment effects
      were 45 m (+13.0 percent), 46 m (+13.3 percent), and 50 m (+14.7 percent) for 20,
      40, and 80 mg of sildenafil, respectively (P<0.001 for all comparisons). All
      sildenafil doses reduced the mean pulmonary-artery pressure (P=0.04, P=0.01, and
      P<0.001, respectively), improved the WHO functional class (P=0.003, P<0.001, and
      P<0.001, respectively), and were associated with side effects such as flushing,
      dyspepsia, and diarrhea. The incidence of clinical worsening did not differ
      significantly between the patients treated with sildenafil and those treated with
      placebo. Among the 222 patients completing one year of treatment with sildenafil
      monotherapy, the improvement from baseline at one year in the distance walked in
      six minutes was 51 m. CONCLUSIONS: Sildenafil improves exercise capacity, WHO
      functional class, and hemodynamics in patients with symptomatic pulmonary
      arterial hypertension.

PMID- 16291986
TI  - Clinical practice. Long-acting methods of contraception.

PMID- 16291985
TI  - Cost-effectiveness of cervical-cancer screening in five developing countries.
AB  - BACKGROUND: Cervical-cancer screening strategies that involve the use of
      conventional cytology and require multiple visits have been impractical in
      developing countries. METHODS: We used computer-based models to assess the cost
      effectiveness of a variety of cervical-cancer screening strategies in India,
      Kenya, Peru, South Africa, and Thailand. Primary data were combined with data
      from the literature to estimate age-specific incidence and mortality rates for
      cancer and the effectiveness of screening for and treatment of precancerous
      lesions. We assessed the direct medical, time, and program-related costs of
      strategies that differed according to screening test, targeted age and frequency,
      and number of clinic visits required. Single-visit strategies involved the
      assumption that screening and treatment could be provided in the same day.
      Outcomes included the lifetime risk of cancer, years of life saved, lifetime
      costs, and cost-effectiveness ratios (cost per year of life saved). RESULTS: The
      most cost-effective strategies were those that required the fewest visits,
      resulting in improved follow-up testing and treatment. Screening women once in
      their lifetime, at the age of 35 years, with a one-visit or two-visit screening
      strategy involving visual inspection of the cervix with acetic acid or DNA
      testing for human papillomavirus (HPV) in cervical cell samples, reduced the
      lifetime risk of cancer by approximately 25 to 36 percent, and cost less than 500
      dollars per year of life saved. Relative cancer risk declined by an additional 40
      percent with two screenings (at 35 and 40 years of age), resulting in a cost per
      year of life saved that was less than each country's per capita gross domestic
      product--a very cost-effective result, according to the Commission on
      Macroeconomics and Health. CONCLUSIONS: Cervical-cancer screening strategies
      incorporating visual inspection of the cervix with acetic acid or DNA testing for
      HPV in one or two clinical visits are cost-effective alternatives to conventional
      three-visit cytology-based screening programs in resource-poor settings.

PMID- 16291987
TI  - Image in clinical medicine. Lentigo maligna.

PMID- 16291988
TI  - Case records of the Massachusetts General Hospital. Case 35-2005. A 56-year-old
      woman with breast cancer and isolated tumor cells in a sentinel lymph node.

PMID- 16291989
TI  - Pharmacotherapy for obesity--promise and uncertainty.

PMID- 16291990
TI  - Erythropoietin as a retinal angiogenic factor.

PMID- 16291991
TI  - Bone marrow micrometastases in breast cancer.

PMID- 16291992
TI  - Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery.

PMID- 16291993
TI  - Lung-cancer screening.

PMID- 16291994
TI  - Case 23-2005: a man with a mass in the liver.

PMID- 16291995
TI  - Obesity and mortality.

PMID- 16291996
TI  - Octadecylated silica monolith capillary column with integrated nanoelectrospray
      ionization emitter for highly efficient proteome analysis.
AB  - An improved strategy for the preparation of octadecylated silica monolith
      capillary column with high homogeneity was proposed. Column performance was
      evaluated by nanoscale HPLC. The design for constructing an integrated
      nanoelectrospray emitter on the octadecylated silica monolith capillary column
      was first introduced. In comparison with the separated configuration where the
      emitter is connected to monolithic capillary column by the aid of a zero dead
      volume union, the integrated capillary column has the inherent advantage of the
      minimized extracolumn volume thus providing improved separation quality. The
      performance of the integrated monolithic capillary column was evaluated by
      separation of BSA tryptic digest, and peak capacity of 313 with a 30-cm column
      was obtained. The high separation performance allowed highly confident
      identification of 662 distinct proteins through assignment of 1933 unique
      peptides by analysis of tryptic digest of 0.5 mug of Saccharomyces cerevisiae
      proteins. The higher separation efficiency by a 60-cm monolithic capillary column
      increased the proteome coverage with identification of 1323 proteins through
      assignment of 5501 unique peptides over 400-min gradient elution.

PMID- 16291997
TI  - Toward the complete membrane proteome: high coverage of integral membrane
      proteins through transmembrane peptide detection.
AB  - To attain a comprehensive membrane proteome of two strains of Corynebacterium
      glutamicum (l-lysine-producing and the characterized model strains), both sample
      pretreatment and analysis methods were optimized. Isolated bacterial membranes
      were digested with trypsin/cyanogen bromide or trypsin/chymotrypsin, and a
      complementary protein set was identified using the multidimensional protein
      identification technology (MudPIT). Besides a distinct number of cytosolic or
      membrane-associated proteins, the combined data analysis from both digests
      yielded 326 integral membrane proteins ( approximately 50% of all predicted)
      covering membrane proteins both with small and large numbers of transmembrane
      helices. Also membrane proteins with a high GRAVY score were identified, and
      basic and acidic membrane proteins were evenly represented. A significant
      increase in hydrophobic peptides with distinctly higher sequence coverage of
      transmembrane regions was achieved by trypsin/chymotrypsin digestion in an
      organic solvent. The percentage of identified membrane proteins increased with
      protein size, yielding 80% of all membrane proteins above 60 kDa. Most
      prominently, almost all constituents of the respiratory chain and a high number
      of ATP-binding cassette transport systems were identified. This newly developed
      protocol is suitable for the quantitative comparison of membrane proteomes and
      will be especially useful for applications such as monitoring protein expression
      under different growth and fermentation conditions in bacteria such as C.
      glutamicum. Moreover with more than 50% coverage of all predicted membrane
      proteins (including the non-expressed species) this improved method has the
      potential for a close-to-complete coverage of membrane proteomes in general.

PMID- 16291998
TI  - In silico identification of new secretory peptide genes in Drosophila
      melanogaster.
AB  - Bioactive peptides play critical roles in regulating most biological processes in
      animals. The elucidation of the amino acid sequence of these regulatory peptides
      is crucial for our understanding of animal physiology. Most of the
      (neuro)peptides currently known were identified by purification and subsequent
      amino acid sequencing. With the entire genome sequence of some animals now
      available, it has become possible to predict novel putative peptides. In this
      way, BLAST (Basic Local Alignment Searching Tool) analysis of the Drosophila
      melanogaster genome has allowed annotation of 36 secretory peptide genes so far.
      Peptide precursor genes are, however, poorly predicted by this algorithm, thus
      prompting an alternative approach described here. With the described searching
      program we scanned the Drosophila genome for predicted proteins with the
      structural hallmarks of neuropeptide precursors. As a result, 76 additional
      putative secretory peptide genes were predicted in addition to the 43 annotated
      ones. These putative (neuro)peptide genes contain conserved motifs reminiscent of
      known neuropeptides from other animal species. Peptides that display sequence
      similarities to the mammalian vasopressin, atrial natriuretic peptide, and
      prolactin precursors and the invertebrate peptides orcokinin, prothoracicotropic
      hormones, trypsin modulating oostatic factor, and Drosophila immune induced
      peptides (DIMs) among others were discovered. Our data hence provide further
      evidence that many neuropeptide genes were already present in the ancestor of
      Protostomia and Deuterostomia prior to their divergence. This bioinformatic study
      opens perspectives for the genome-wide analysis of peptide genes in other
      eukaryotic model organisms.

PMID- 16291999
TI  - The platypus is in its place: nuclear genes and indels confirm the sister group
      relation of monotremes and Therians.
AB  - Morphological data supports monotremes as the sister group of Theria (extant
      marsupials + eutherians), but phylogenetic analyses of 12 mitochondrial protein
      coding genes have strongly supported the grouping of monotremes with marsupials:
      the Marsupionta hypothesis. Various nuclear genes tend to support Theria, but a
      comprehensive study of long concatenated sequences and broad taxon sampling is
      lacking. We therefore determined sequences from six nuclear genes and obtained
      additional sequences from the databases to create two large and independent
      nuclear data sets. One (data set I) emphasized taxon sampling and comprised five
      genes, with a concatenated length of 2,793 bp, from 21 species (two monotremes,
      six marsupials, nine placentals, and four outgroups). The other (data set II)
      emphasized gene sampling and comprised eight genes and three proteins, with a
      concatenated length of 10,773 bp or 3,669 amino acids, from five taxa (a
      monotreme, a marsupial, a rodent, human, and chicken). Both data sets were
      analyzed by parsimony, minimum evolution, maximum likelihood, and Bayesian
      methods using various models and data partitions. Data set I gave bootstrap
      support values for Theria between 55% and 100%, while support for Marsupionta was
      at most 12.3%. Taking base compositional bias into account generally increased
      the support for Theria. Data set II exclusively supported Theria, with the
      highest possible values and significantly rejected Marsupionta. Independent
      phylogenetic evidence in support of Theria was obtained from two single amino
      acid deletions and one insertion, while no supporting insertions and deletions
      were found for Marsupionta. On the basis of our data sets, the time of divergence
      between Monotremata and Theria was estimated at 231-217 MYA and between
      Marsupialia and Eutheria at 193-186 MYA. The morphological evidence for a basal
      position of Monotremata, well separated from Theria, is thus fully supported by
      the available molecular data from nuclear genes.

PMID- 16292001
TI  - Quantitative analysis of the corticocortical projections to the middle temporal
      area in the marmoset monkey: evolutionary and functional implications.
AB  - The connections of the middle temporal area (MT) were investigated in the
      marmoset, one of the smallest primates. Reflecting the predictions of studies
      that modeled cortical allometric growth and development, we found that in adult
      marmosets MT is connected to a more extensive network of cortical areas than in
      larger primates, including consistent connections with retrosplenial, cingulate,
      and parahippocampal areas and more widespread connections with temporal, frontal,
      and parietal areas. Quantitative analyses reveal that MT receives the majority of
      its afferents from other motion-sensitive areas in the temporal lobe and from the
      occipitoparietal transition areas, each of these regions containing approximately
      30% of the projecting cells. Projections from the primary visual area (V1) and
      the second visual area (V2) account for approximately 20% of projecting neurons,
      whereas "ventral stream" and higher-order association areas form quantitatively
      minor projections. A relationship exists between the percentage of supragranular
      layer neurons forming the projections from different areas and their putative
      hierarchical rank. However, this relationship is clearer for projections from
      ventral stream areas than it is for projections from dorsal stream or frontal
      areas. These results provide the first quantitative data on the connections of MT
      and extend current understanding of the relationship between cortical anatomy and
      function in evolution.

PMID- 16292000
TI  - From DNA to fitness differences: sequences and structures of adaptive variants of
      Colias phosphoglucose isomerase (PGI).
AB  - Colias eurytheme butterflies display extensive allozyme polymorphism in the
      enzyme phosphoglucose isomerase (PGI). Earlier studies on biochemical and fitness
      effects of these genotypes found evidence of strong natural selection maintaining
      this polymorphism in the wild. Here we analyze the molecular features of this
      polymorphism by sequencing multiple alleles and modeling their structures. PGI is
      a dimer with rotational symmetry. Each monomer provides a critical residue to the
      other monomer's catalytic center. Sequenced alleles differ at multiple amino acid
      positions, including cryptic charge-neutral variation, but most consistent
      differences among the electromorph alleles are at the charge-changing amino acid
      sites. Principal candidate sites of selection, identified by structural and
      functional analyses and by their variants' population frequencies, occur in
      interpenetrating loops across the interface between monomers, where they may
      alter subunit interactions and catalytic center geometry. Comparison to a second
      (and basal) species, Colias meadii, also polymorphic for PGI under natural
      selection, reveals one fixed amino acid difference between their PGIs, which is
      located in the interpenetrating loop and accompanies functional differences among
      their variants. We also study nucleotide variability among the PGI alleles,
      comparing these data to similar data from another glycolytic enzyme gene,
      glyceraldehyde-3-phosphate dehydrogenase. Despite extensive nonsynonymous and
      synonymous polymorphism at PGI in each species, the only base changes fixed
      between species are the two causing the amino acid replacement; this absence of
      synonymous fixation yields a significant McDonald-Kreitman test. Analyses of
      these data suggest historical population expansion. Positive peaks of Tajima's D
      statistic, representing regions of neutral "hitchhiking," are found around the
      principal candidate sites of selection. This study provides novel views of
      molecular-structural mechanisms, and beginnings of historical evidence, for a
      long-persistent balanced enzyme polymorphism at PGI in these and perhaps other
      species.

PMID- 16292002
TI  - Heterotopia formation in rat but not mouse neocortex after RNA interference
      knockdown of DCX.
AB  - Subcortical band heterotopia (SBH) or double cortex is associated with
      significant impairments in neocortical function including mental retardation and
      epilepsy. Mutant alleles of DCX in humans typically cause SBH in females and
      lissencephaly in males, whereas Dcx null mutations in mice neither disrupt
      neocortical neuronal migration nor cause SBH formation. In utero RNA interference
      (RNAi) of Dcx in rats, in contrast, creates an animal model of SBH. Possible
      explanations for the discrepancies in results following loss of Dcx function
      include species differences and/or differences between RNAi knockdown and genetic
      deletion. We have carried out a series of in utero RNAi experiments to
      investigate possible species differences between rat and mouse to determine the
      molecular specificity of RNAi against Dcx and to identify the cellular
      constituents of SBH in the rat model. In utero RNAi in the rat consistently leads
      to both the formation of SBH and laminar displacement of transfected cells in
      normotopic cortex, whereas the same treatment in mouse fails to induce SBH but
      does create laminar displacement. Induction of SBH and impaired radial migration
      following RNAi against Dcx is rescued by overexpression of Dcx. Thus, both
      disruptions induced by RNAi are specific to interference of Dcx. SBHs contain
      transfected pyramidal cells as well as nontransfected cell types, including
      neocortical interneurons and glia. Together these results indicate that there is
      a species difference between rat and mouse with respect to RNAi-induced SBH
      formation and that SBH formation involves the recruitment of several unaltered
      cell types.

PMID- 16292003
TI  - Decreased input-specific plasticity of the auditory cortex in mice lacking M1
      muscarinic acetylcholine receptors.
AB  - Muscarinic acetylcholine receptors are extensively involved in cortical cognition
      and learning-induced or experience-dependent cortical plasticity. The most
      abundant muscarinic receptor subtype in the cerebral cortex is the M1 receptor,
      but little is known about its contribution to experience-dependent plasticity of
      the adult auditory cortex. We have examined the role of the M1 receptor in
      experience-dependent plasticity of the auditory cortex in mice lacking the M1
      (chrm1) gene. We show here that electrical stimulation of the basal forebrain, a
      major source of cortical cholinergic inputs, facilitated the auditory responses
      of cortical neurons in both wild types and M1 mutants. The basal forebrain
      stimulation alone caused change in the best frequencies of cortical neurons that
      were significantly greater in M1 mutants. When animals received the paired
      stimuli of electrical stimulation of the basal forebrain and tone, the frequency
      tuning of cortical neurons systematically shifted toward the frequency of the
      paired tone in both wild types and M1 mutants. However, the shift range in M1
      mutants was much smaller than that in wild-type mice. Our data suggest that the
      M1 receptor is important for the experience-dependent plasticity of the auditory
      cortex.

PMID- 16292005
TI  - The contingencies of organizational learning in long-term care: factors that
      affect innovation adoption.
AB  - We apply the theoretical frameworks of knowledge transfer and organizational
      learning, and findings from studies of clinical practice guideline (CPG)
      implementation in health care, to develop a contingency model of innovation
      adoption in long-term care (LTC) facilities. Our focus is on a particular type of
      innovation, CPGs designed to improve the quality of LTC. Our interest in this
      area is founded on the premise that the ability of LTC organizations to adopt and
      sustain the use of innovations like CPGs is contingent on the initial capacity
      these institutions have to learn about them, and on the presence of factors that
      contribute to capacity building at each stage of innovation adoption. Based on
      our review of relevant theory, we develop a set of fifteen testable propositions
      that relate factors operating at the guideline, individual, organizational, and
      environmental levels in LTC institutions to stages of guideline
      adoption/transfer. Our model offers insights into the complexities of adopting
      and sustaining innovations in LTC facilities particularly, in health care
      organizations specifically, and in service organizations generally.

PMID- 16292007
TI  - A study of thematic content in hospital mission statements: a question of values.
AB  - We examined the content of Canadian hospital mission statements using thematic
      content analysis. The mission statements that we studied varied in terms of both
      content and length. Although there was some content related to goals designed to
      ensure organizational visibility, survival, and competitiveness, the domain of
      values predominated over our entire coding structure. The primary value-related
      theme that emerged concerned the importance of patient care.

PMID- 16292006
TI  - Environmental assessment of the Indian health service.
AB  - The Indian Health Service (IHS), an agency within the U.S. Department of Health
      and Human Services, was responsible for providing federal health services to 1.51
      million American Indian and Alaska Natives in 2000. Several opportunities related
      to health care exist for the IHS: potential public and private collaborations,
      continuation of the Clinton Administration's legacy of meaningful tribal
      consultation, and increasing the numbers of American Indian physicians, nurses,
      and other health related professionals. Modifications in federal programs such as
      Medicare and Medicaid pose a serious threat to the IHS because the IHS relies on
      these programs to offset the overall lack of funding. This article provides a
      framework for identifying the ways in which the external environment affects and
      determines the IHS' strategic responses to ensure competitiveness within the U.S.
      health care market. Value chain analysis will be used to evaluate the competitive
      advantages and disadvantages of the current IHS internal environment.

PMID- 16292008
TI  - Uncompensated care provided by emergency physicians in Florida emergency
      departments.
AB  - Uncompensated emergency department (ED) visits can negatively affect patients,
      clinicians, and hospitals, particularly as overcrowding occurs. Florida provides
      a unique market to analyze uncompensated ED care due to the high percent of for
      profit hospitals, which typically provide significantly less uncompensated care,
      coupled with the older population that is more likely to be insured through
      Medicare. A survey of 188 Florida hospital emergency physician groups was
      conducted to estimate the level of uncompensated care provided by each ED
      physician group in 1998. The response rate was 44 percent (eighty-three ED
      physician groups). All ED physician groups provided substantial uncompensated
      care regardless of hospital ownership type. Uncompensated care averaged 46.8
      percent and ranged from 25.8 to 79.4 percent. A model was developed to predict
      the amount of uncompensated care using ED volume and payer mix. A rise in the
      percent of self-pay patients causes a disproportionate increase in uncompensated
      care, such that EDs with high levels of self-pay visits have markedly higher
      uncompensated care rates. The results suggest the need for a uniform reporting
      method of ED physician uncompensated care cost.

PMID- 16292009
TI  - Medicine's service challenge: blending custom and standard care.
AB  - Health care, once resolutely customized, is now a process comprising an
      uncomfortable mix of custom and standard elements. Although the operations
      management literature often advocates the separation of custom and standard
      processes, health care managers must usually provide both simultaneously,
      attempting to combine the two types of service process within a single
      organization dynamically. If this is not done effectively, quality of care can
      suffer. Using examples drawn from health care delivery, this paper introduces
      three operational strategies for effectively combining custom and standard
      clinical processes. The choice of operating strategy depends on the nature of the
      patient's needs and the state of medical knowledge.

PMID- 16292010
TI  - "I'm gonna do what i wanna do." Organizational change as a legitimized vehicle
      for bullies.
AB  - In-depth interviews with nurses who have been bullied depict bullies masking
      their bullying behavior behind the cloak of legitimate organizational processes,
      resulting in extensive harm to targets.

PMID- 16292011
TI  - Is it resources, habit or both: interpreting twenty years of hospital strategic
      response to prospective payment.
AB  - The 1983 Tax Equity and Fiscal Responsibility Act (TEFRA) transformed acute care
      from a benevolent to malevolent environment. A dual-paradigm of resource
      dependency and institutional theories that balances isomorphic with economic
      variables has emerged to better explain hospital strategic response to the
      resultant constraint on resources than a traditional single paradigm approach.
      Using the population of non-rural, non-federal acute-care hospitals, strategic
      response from 1982 to 2001 is studied; distinct cost and service changes occur.
      Cost strategy is linked primarily to Medicare utilization, a resource dependence
      response. Service strategy favors high technology regardless of prospective
      payment diffusion, an institutional theory perspective. Strategic implications
      are discussed.

PMID- 16292012
TI  - Comparing high- and low-performing hospitals using risk-adjusted excess mortality
      and cost inefficiency.
AB  - This study examines characteristics associated with high- and low-performing
      hospitals, where performance is defined in terms of both mortality outcomes and
      efficiency. In particular, we use data for Florida hospitals in 1999-2001 to
      classify hospitals into performance groups based on both risk-adjusted excess
      mortality and cost efficiency. The results indicate that hospitals in the high
      performing group were more likely to be for-profit, had higher occupancy rates,
      had proportionately more Medicare and proportionately fewer Medicaid and self-pay
      patients, used fewer patient-care personnel per admission, and had higher
      operating margins than all other hospitals. Hospitals in the low-performing
      group, on the other hand, were less likely to be for-profit, had more beds, used
      more patient-care personnel per admission, had lower pay per patient-care
      personnel, had higher average costs, and had lower operating margins than all
      other hospitals. Interestingly, managed care presence, measured by proportion of
      HMO-PPO admissions, was not a significant factor in differentiating hospital
      performance groups.

PMID- 16292013
TI  - Improving outpatient health care quality: understanding the quality dimensions.
AB  - Based on literature review, we derive a set of dimensions that influence patient
      perceived health care quality. Utilizing outpatient survey data from 222
      different physicians, we identified six underlying quality factors and classified
      them according to the derived dimensions. These quality factors explain
      approximately 51 percent of the variation in overall patient-perceived health
      care quality.

PMID- 16292014
TI  - Linking nursing home working conditions to organizational performance.
AB  - Exploring selected working conditions and performance in nursing homes suggests
      that high and low performers can be determined based on both quantitative and
      qualitative findings.

PMID- 16292016
TI  - Medical futility in the natural attitude.
AB  - Medical futility has a long history going back to Plato but continues to be a
      controversial topic. Patients, families, and health professionals are faced with
      decisions about which treatments and interventions may be futile, but such
      questions as who decides; how do competing values get resolved; what value is
      placed on human life; how are decisions balanced according to reason and, in some
      circumstances, faith; and who decides effect, benefit, and burdens of treatments
      are often difficult to answer. The naive reality of medical futility is explored
      in the natural attitude to expose presumptions and facts related to both
      physiologic (fact-based) and evaluative (value-based) futility components.
      Highlights from the bioethical and clinical literature, a review of 3 landmark
      cases, and implications for nursing practice are presented. This natural attitude
      description could serve as what ought to be bracketed for a future phenomenology.

PMID- 16292017
TI  - Predicting immune status in women from PTSD and childhood and adult violence.
AB  - This study uses a predictive exploratory design to test the relationships between
      and among childhood maltreatment, intimate partner violence (IPV), posttraumatic
      stress disorder (PTSD) symptoms, and immune status in abused women. A convenience
      sample of 126 abused women and 12 nonabused women matched for age and
      race/ethnicity were recruited. The woman's current smoking habit, history of
      childhood maltreatment, experience of IPV, and PTSD symptoms predicted immune
      status. This prediction occurs through both direct and indirect pathways from IPV
      to immune status and from IPV to immune status through PTSD.

PMID- 16292018
TI  - Implementing a comprehensive approach to the study of health dynamics using the
      psychoneuroimmunology paradigm.
AB  - This article addresses psychoneuroimmunology (PNI) as an integrative paradigm for
      advancing both theoretical and empirical knowledge of physiological patterns that
      contribute to the dynamics of health. We depict relationships among relevant
      psychobehavioral and physiological components in a PNI-based framework. We then
      provide examples of how this framework guided 2 clinical trials designed to
      assess the effectiveness of selected nursing interventions to reduce stress and
      enhance coping, one in persons with human immunodeficiency viral disease and the
      other in persons with cancer. The examples address disease-specific measures for
      assessing the components of the PNI-based framework.

PMID- 16292019
TI  - Symptom management in HIV/AIDS: advancing the conceptualization.
AB  - For people living with HIV, symptoms related to the disease, comorbidities, and
      treatment side effects make symptom management essential. Poorly managed symptoms
      result in reduced medication adherence, disease progression, and lower quality of
      life. The Self-regulatory HIV/AIDS Symptom Management Model is a conceptual model
      that describes how persons living with HIV/AIDS manage their symptoms. The model
      links symptom experience, symptom management, social support, adherence, and
      health-related quality of life. It can assist nurses, through a multidimensional
      approach to illness management, to enhance symptom assessment, better understand
      factors influencing symptom experience, and to improve symptom management among
      people living with HIV/AIDS.

PMID- 16292020
TI  - Effects of maternal prenatal stress on infant outcomes: a synthesis of the
      literature.
AB  - There is growing evidence that maternal prenatal stress may be hazardous to
      infant health. Changes in maternal hormonal and immune function as a result of
      stress may adversely affect the immune function and neurodevelopment of the
      fetus. Prenatal stress in the mother may produce lasting effects on the (1)
      infant's health status, (2) development and function of the infant's immune
      system, and (3) neurocognitive development of the infant. This article provides a
      synthesis of current human and animal literature on the effects of maternal
      prenatal stress on the developing fetus and the infant, with the resulting model
      evolving out of the framework of psychoneuroimmunology. The intent of the authors
      is an integrative review. The authors examined the following research question:
      What effect does maternal prenatal stress have on infants' immune development and
      neurodevelopment? All relevant studies were reviewed with no exclusion criteria.
      Major databases (CINAHL, MEDLINE, PsychINFO) were searched using a combination of
      the following key words: prenatal stress, cytokines, thymus, and infant
      neurodevelopment.

PMID- 16292021
TI  - Development of preterm infants: feeding behaviors and brazelton neonatal
      behavioral assessment scale at 40 and 44 weeks' postconceptional age.
AB  - The purpose of this study was twofold: (1) to explore potential changes in the
      Brazelton Neonatal Behavioral Assessment Scale (BNBAS) from 40 to 44 weeks
      postconceptional age (PCA) and (2) to determine the relationship between the
      BNBAS scores and feeding behaviors in preterm infants at 40 and 44 weeks PCA. The
      BNBAS and sucking behavior measurements were completed on 104 preterm infants at
      40 and 44 weeks PCA. The Orientation (p = .001), Motor (p = .001), Range of State
      (p = .001), Autonomic Regulation (p = .01), and Reflexes (p = .00) clusters were
      significantly more mature at 44 weeks PCA than at 40 weeks. Infants that were
      extremely early born (n = 24) had a significantly larger change in BNBAS scores
      over time as compared to the more mature preterm infants (n = 77), largely
      catching up with their more mature preterm counterparts. At 40 and 44 weeks PCA,
      the BNBAS cluster scores for orientation (p = .02), motor (p = .048), range of
      state (p = .048), and regulation of state (p < .001) were significantly related
      to the average maximum pressure, adjusted for gestational age and weeks PCA.
      Significant neurobehavioral maturation takes place between 40 and 44 weeks PCA in
      preterm infants, with the greatest changes occurring in the most preterm infants.
      These findings highlight the relationship between neurobehavioral maturation and
      feeding behaviors.

PMID- 16292022
TI  - Estrogen-related mood disorders: reproductive life cycle factors.
AB  - Women are at higher risk throughout their reproductive lives than are men for
      major depression. Numerous molecular and clinical studies have implicated
      estrogen in modulating brain function including that related to mood. In an
      attempt to present a conceptual model, the literature of the past 30 years on
      mood and well-being throughout reproductive life is reviewed as it relates to
      activity of endogenous, bio-identical, and synthetic estrogen in women. Results
      indicate that sudden estrogen withdrawal, fluctuating estrogen, and sustained
      estrogen deficit are correlated with significant mood disturbance. Clinical
      recovery from depression postpartum, perimenopause, and postmenopause through
      restoration of stable/optimal levels of estrogen has been noted.

PMID- 16292041
TI  - Widespread adoption of health information technology could save $162 billion a
      year, but the federal government needs to help.

PMID- 16292043
TI  - Evaluation of user interface satisfaction of a clinical outcomes database.
AB  - Interface design and usability testing are important skills for the informatics
      nurse. This study used the Questionnaire for User Interaction Satisfaction
      (QUIStrade mark) to evaluate a nurse practitioner outcomes database used to track
      client variables for evaluating clinical outcomes and for implementing a process
      improvement project. Five nursing faculty and students were instructed in the use
      of the database and subsequently evaluated the usability or "ease of use" of the
      interface (data entry screens). The mean on individual QUIS ratings ranging from
      3.0 to 8.0 on a 9-point scale, although most mean ratings were moderately high.
      User comments identified specific areas for improvement in the interface.
      Discovering problem areas and modifying the screen design prior to deployment may
      increase the usability of the database and decrease user frustration.

PMID- 16292023
TI  - Dynamics of nutritional health in a community sample of american elders: a
      multidimensional approach using roy adaptation model.
AB  - Nutritional health of community-dwelling elders has been shown to be one of the
      prime indices of health, influencing the elders' ability to live independently.
      However, little research has been directed toward understanding the dynamics of
      nutritional health in community-dwelling elders using a multidimensional theory
      approach. The purpose of this study was to evaluate the dynamics of nutritional
      health within the context of Roy Adaptation Model. Factors associated with
      nutritional health of community-dwelling elders were cross-examined. Depressive
      symptoms, functional status, oral health, and income emerged as independent
      predictors of nutritional health adjusting for confounders. This finding lends
      support to the notion that multidimensional biopsychosocial factors contribute to
      the dynamics of nutritional health.

PMID- 16292044
TI  - Interdisciplinary collaboration: an effective approach for developing web-based
      courses.
AB  - Nursing faculty often perceive that developing Web-based distance education
      courses is very time consuming, while others believe they lack the necessary
      pedagogical skills. This article describes an interdisciplinary collaborative
      approach to developing a Web-based distance education course in an academic
      health science center. This strategy effectively supported faculty in learning
      new skills and resulted in a highly satisfying experience for faculty and
      students.

PMID- 16292046
TI  - A simple, flexible and scalable approach for generating tailored questionnaires
      and health education messages.
AB  - Tailored health information is important for generating patient-specific
      recommendations in clinical decision support systems and for crafting health
      education materials that are specifically customized to a patient. Many previous
      attempts to generate tailored information require complex representations, lack
      general applicability, and are inflexible to content alterations. In this
      article, we describe a simple, yet flexible approach for tailoring health
      communication. This generalized and scalable approach relies on a flexible state
      representation of each individual and an expandable rule drafting and processing
      engine. It utilizes a relational database schema and a simple table structure to
      maintain each individual's past and current health information. Content for
      tailored communication is represented in a single table which stores predefined
      logic describing the rules for selecting content applicable to specific
      individuals. The flexibility, scalability, and simplicity of this approach are
      demonstrated by describing two diverse projects. One project has provided patient
      tailored decision support for physicians for over 82,000 patient encounters and
      the other generates tailored health questions and messages for patients through a
      tool developed in less than 4 months.

PMID- 16292047
TI  - Best practices in NCLEX-RN readiness preparation for baccalaureate student
      success.
AB  - Success for first-time takers of the NCLEX-RN has implications for the students,
      faculty, and nursing programs. As the passing standard for the NCLEX-RN has
      risen, some programs have experienced a corresponding decrease in their
      graduates' first-time pass rates. This article describes one baccalaureate
      program's journey from low first-time NCLEX-RN pass rates in 2001 to greater
      student and program success using a data-based, analytical approach. Although
      passing an exit exam was a program requirement for 20 years, the change to
      computerized testing and more in-depth test preparation has enhanced
      opportunities for success for students and reduced stress among faculty. The
      resulting best practices for preparing students for NCLEX-RN success are
      described.

PMID- 16292048
TI  - Synchronous computer mediated group discussion.
AB  - Over the past 20 years, focus groups have become increasingly popular with
      nursing researchers as a data collection method, as has the use of computer-based
      technologies to support all forms of nursing research. This article describes the
      conduct of a series of focus groups in which the participants were in the same
      room as part of a "real-time" discussion during which they also used personal
      computers as an interface between each other and the moderator. Synchronous
      Computer Mediated Group Discussion differed from other forms of focus group
      discussion in that participants used personal computers rather than verbal
      expressions to respond to specific questions, engage in communication with other
      participants, and to record their thoughts. This form of focus group maintained
      many of the features of spoken exchanges, a cornerstone of the focus group, while
      capturing the advantages of online discussion.

PMID- 16292049
TI  - Heart rate variability analysis: a tool to assess cardiac autonomic function.
AB  - Heart rate monitoring is commonly used to provide an acute indicator of an
      individual's cardiovascular status and responsiveness. An increasingly popular
      technique involves quantifying the very small amounts by which the heart rate
      changes from one cardiac cycle to the next. This "heart rate variability (HRV)
      analysis" provides a substantial amount of additional information about the
      cardiovascular system and enables quantification of cardiac regulatory influences
      on the autonomic nervous system. The autonomic nervous system consists of two
      main components: the sympathetic system and the parasympathetic system. The
      relative influence of these two components on the sino-atrial node of the heart
      determines the heart rate. A number of physiological factors, including blood
      pressure and respiratory rate, can have a profound effect on this autonomic
      "balance." HRV analysis therefore provides a noninvasive method for investigating
      the dynamic influence of changing physiological parameters on cardiac regulation.

PMID- 16292053
TI  - Acute renal failure, interdisciplinary knowledge and the need for
      standardization.

PMID- 16292054
TI  - Consensus development in acute renal failure: The Acute Dialysis Quality
      Initiative.
AB  - PURPOSE OF REVIEW: Although acute renal failure is both common and highly lethal
      in the intensive care unit, our understanding of the epidemiology and
      pathophysiology of acute renal failure is limited, and treatment for acute renal
      failure is extremely variable around the world. The general lack of consensus
      with regard to definitions, prevention, and treatment of acute renal failure has
      limited progress in this field. RECENT FINDINGS: Consensus in acute renal failure
      requires establishing a framework in which intensivists, nephrologists,
      pharmacologists, and others who care for critically ill patients with or at risk
      for acute renal failure can reach consensus and develop evidence-based practice
      guidelines. The Acute Dialysis Quality Initiative seeks to provide an objective,
      dispassionate distillation of the literature and description of the current state
      of practice of dialysis and related therapies as they are applied to acutely ill
      patients. The purposes of Acute Dialysis Quality Initiative are first, to develop
      a consensus of opinion, with evidence where possible, on best practice; and
      second, to articulate a research agenda to focus on important unanswered
      questions. SUMMARY: Broad consensus in the diagnosis and management of acute
      renal failure and in the use of blood purification in nonrenal critical illness
      is achievable. Standardization of definitions, practice, and research methodology
      is urgently needed, and specific proposals have been made by an international,
      interdisciplinary group.

PMID- 16292055
TI  - Risk factors for acute renal failure: inherent and modifiable risks.
AB  - PURPOSE OF REVIEW: Our purpose is to discuss established risk factors in the
      development of acute renal failure and briefly overview clinical markers and
      preventive measures. RECENT FINDINGS: Findings from the literature support the
      role of older age, diabetes, underlying renal insufficiency, and heart failure as
      predisposing factors for acute renal failure. Diabetics with baseline renal
      insufficiency represent the highest risk subgroup. An association between sepsis,
      hypovolemia, and acute renal failure is clear. Liver failure, rhabdomyolysis, and
      open-heart surgery (especially valve replacement) are clinical conditions
      potentially leading to acute renal failure. Increasing evidence shows that
      intraabdominal hypertension may contribute to the development of acute renal
      failure. Radiocontrast and antimicrobial agents are the most common causes of
      nephrotoxic acute renal failure. In terms of prevention, avoiding nephrotoxins
      when possible is certainly desirable; fluid therapy is an effective prevention
      measure in certain clinical circumstances. Supporting cardiac output, mean
      arterial pressure, and renal perfusion pressure are indicated to reduce the risk
      for acute renal failure. Nonionic, isoosmolar intravenous contrast should be used
      in high-risk patients. Although urine output and serum creatinine lack
      sensitivity and specificity in acute renal failure, they remain the most used
      parameters in clinical practice. SUMMARY: There are identified risk factors of
      acute renal failure. Because acute renal failure is associated with a worsening
      outcome, particularly if occurring in critical illness and if severe enough to
      require renal replacement therapy, preventive measures should be part of
      appropriate management.

PMID- 16292056
TI  - Primary prevention of acute renal failure in the critically ill.
AB  - PURPOSE OF REVIEW: Acute renal failure is both common and highly lethal in the
      intensive care unit, with hospital mortality rates in excess of 50%. To date, no
      therapy apart from renal replacement therapy has been shown to improve survival
      or enhance recover. Thus, efforts to prevent acute renal failure are eagerly
      sought. RECENT FINDINGS: Fluids and avoiding hypotension and nephrotoxins appear
      to be the most effective strategies to prevent acute renal failure. N
      acetylcysteine has been shown to prevent the increase in serum creatinine in high
      risk patients given intravenous radiocontrast agents, although there is some
      evidence that N-acetylcysteine may reduce serum creatinine without increasing
      glomerular filtration. SUMMARY: The best evidence suggests that nonpharmacologic
      strategies are more effective than drugs in reducing the risk of acute renal
      failure. Evidence also exists that strategies that improve survival in critically
      ill patients also reduce the incidence of organ failure, including acute renal
      failure.

PMID- 16292057
TI  - Management of early acute renal failure: focus on post-injury prevention.
AB  - PURPOSE OF REVIEW: In this review, we describe our current understanding of
      various aspects of secondary renal injury and its prevention. Secondary renal
      injury indicates any injury to the kidney, which occurs after an initial event
      has already triggered injury to the organ. RECENT FINDINGS: Analysis of the
      literature reveals several important fields of possible intervention. First,
      blood pressure is considered important and hypotension is associated with renal
      injury. Avoiding hypotension is an important mechanism of renal protection from
      secondary injury. Similarly, a low cardiac output state should be promptly
      treated or prevented. Adequate volume resuscitation is also considered important
      although strong direct evidence for this intervention is not available. There is
      insufficient evidence to suggest that any drug can specifically increase renal
      blood flow in man independent of an effect on blood pressure or cardiac output.
      Specific kidney protective approaches have not yet been identified. Intensive
      insulin therapy possibly delivers renal protection and deserves further
      investigation. Modulation of the stress response appears attractive in
      experimental models but it has not been shown effective in man. Ischemic
      preconditioning is a useful strategy for renal protection in the experimental
      setting. An understanding of the mechanisms involved in ischemic preconditioning
      might assist in developing novel and effective interventions in man. SUMMARY: The
      pillars of protection from secondary renal injury are similar to those needed to
      protect the kidney from primary injury: maintenance of adequate intravascular
      volume, cardiac output, and arterial blood pressure. Novel protective strategies
      such as intensive insulin therapy require further investigation.

PMID- 16292058
TI  - Renal replacement therapy and the kidney: minimizing the impact of renal
      replacement therapy on recovery of acute renal failure.
AB  - PURPOSE OF REVIEW: Although renal replacement therapy is the mainstay of
      supportive care in patients with severe acute renal failure, its performance can
      have untoward effects that contribute to the prolongation of renal failure or
      impede the ultimate recovery of renal function. In this review, we categorize the
      major complications associated with renal replacement therapy and assess their
      impact on recovery of renal function. RECENT FINDINGS: The major mechanisms by
      which renal replacement therapy is postulated to delay renal recovery include
      treatment-associated hemodynamic instability, vascular catheter-related
      bacteremia and sepsis, and cytokine activation by bioincompatible membranes.
      Clinical data regarding the role of dialysis catheter infections in delay of
      renal recovery are lacking. The data regarding the role of membrane
      biocompatibility and the modality and dose of renal replacement therapy are
      limited and conflicting. SUMMARY: Clinical recommendations must be limited to the
      broad admonishment that complications during renal replacement therapy, including
      hemodynamic instability and catheter-related bacteremia, be minimized by using
      best clinical practices, while recognizing that the impact of specific practices
      on recovery of renal function have not been evaluated. The data do not support
      recommendations regarding utilization of specific membranes or the modality or
      dose of renal replacement therapy on the basis of their impact on recovery of
      renal function.

PMID- 16292059
TI  - Drug-induced acute kidney injury.
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe the most prevalent
      mechanisms of drug-induced acute kidney injury, to define the risk factors for
      nephrotoxicity, and to analyze the available evidence for preventive measures.
      RECENT FINDINGS: Drug toxicity remains an important cause of acute kidney injury
      that, in many circumstances, can be prevented or at least minimized by vigilance
      and early intervention. Recent studies have resulted in increased insight into
      the subcellular mechanisms of drug nephrotoxicity. Further improvement is to be
      expected from the identification of early markers of nephrotoxicity and an
      increasing involvement of a clinical pharmacist. SUMMARY: The main mechanisms of
      nephrotoxicity are vasoconstriction, altered intraglomerular hemodynamics,
      tubular cell toxicity, interstitial nephritis, crystal deposition, thrombotic
      microangiopathy, and osmotic nephrosis. Before prescribing a potentially
      nephrotoxic drug, the risk-to-benefit ratio and the availability of alternative
      drugs should be considered. Modifiable risk factors should be corrected. The
      correct drug dosage should be prescribed. Patients should be pre-hydrated and the
      glomerular filtration rate should be frequently monitored during the
      administration of a potentially nephrotoxic drug. Studies are needed to further
      elucidate the mechanisms of nephrotoxicity to design more-rational prevention and
      treatment strategies. Computer-based prescriber-order entry and an appropriately
      trained intensive care unit pharmacist are particularly helpful to minimize
      medication errors and adverse drug events.

PMID- 16292060
TI  - Challenging problems in surgical critical care.

PMID- 16292061
TI  - Strengthening trauma and critical care globally.
AB  - PURPOSE OF REVIEW: Trauma is an increasingly significant health problem globally,
      especially in low-income and middle-income countries. Trauma care is often
      compromised by economic restrictions. Many capable individuals are attempting to
      meet this challenge in their own countries, however. This review summarizes such
      efforts and assesses how they might be expanded in a comprehensive, global
      fashion. RECENT FINDINGS: Options for improving trauma care in the prehospital
      setting have been explored, including strengthening existing, basic formal
      emergency medical services (including ambulances); instituting new formal
      emergency medical services, where none had previously existed; and exploring
      novel ways to strengthen existing, although informal, systems of prehospital care
      when formal emergency medical services would be unfeasible. Affordable ways by
      which to strengthen hospital care have been addressed for several specific
      injuries, including open fractures, burns, and vascular injuries. Especially
      notable are growing efforts to better monitor outcomes and address factors
      contributing to preventable deaths. The Essential Trauma Care Project has defined
      and promoted core essential trauma care services that every injured person in the
      world realistically can and should be able to receive. This project is a
      collaborative effort of the World Health Organization and the International
      Society of Surgery. SUMMARY: Individual efforts must be built upon to make
      progress in a comprehensive, global fashion. This review summarizes the
      background, achievements, and future potential of the Essential Trauma Care
      Project and several related efforts.

PMID- 16292062
TI  - Trauma systems in Europe.
AB  - PURPOSE OF REVIEW: The purpose of this review is to evaluate the current state
      and recent developments of trauma systems in Europe. RECENT FINDINGS: The
      introduction of a pilot trauma system in the United Kingdom seemed to halve the
      mortality rate in 6 years. This improvement was thought to result, at least in
      part, from improved patient care. A comparison of United States and French trauma
      systems suggested equivalent outcomes among patients who survive to reach the
      hospital. Epidemiologic studies from Europe show an incidence of 30 to 52 per
      1,00,000 per year of major trauma (Injury Severity Score above 15), the vast
      majority of injuries caused by blunt trauma. The total economic costs of traffic
      accidents in European countries vary from approximately 7,500 US dollars to
      1,20,000 US dollars per injury. SUMMARY: There is little original research on
      trauma systems in Europe, although some positive effects on mortality of trauma
      system creation are reported. The level of trauma system development in Europe
      shows great country-by-country variation. It seems to be in a more advanced stage
      in the central European countries and less developed in other countries,
      including the Scandinavian countries, the Baltic states, the United Kingdom, and
      the Mediterranean countries. In general, specialized trauma surgery training is
      more advanced in countries with a higher level of trauma system development.

PMID- 16292063
TI  - Conventional terrorist bomb incidents and the intensive care unit.
AB  - PURPOSE OF REVIEW: A terror bombing creates a momentary stress on acute care
      services, including the emergency medical system, emergency departments, and
      intensive care units. A knowledge of the progression of events, the anticipated
      volume of injured survivors, and the pattern of injuries will enable the
      physician in the intensive care unit to prepare the unit quickly and efficiently
      for the expected rush of injured survivors. RECENT FINDINGS: In the past 2 years
      it has become apparent in the medical literature that terror bombing causes more
      complicated injuries than other types of trauma. The injuries are a combination
      of blast, penetrating, and blunt trauma, as well as burns. As a result, a
      significant number of patients will need care in the intensive care unit for a
      long time. Treating these injuries mandates an understanding of the combination
      of injury mechanisms because the ideal treatment for one mechanism might cause
      harm if another coexists. In addition, recent literature delineates the volume of
      admissions an intensive care unit should anticipate. This information should
      allow the preparation of sufficient vacant intensive care unit beds and
      facilitate the efficient use of equipment and personnel. SUMMARY: This review,
      based on recently published data, aims to provide the intensive care unit
      physician with crucial information about the anticipated progression of events,
      the possible numbers of patients, and the nature of their injuries after a
      terrorist bombing. This information should aid in rational crisis planning.

PMID- 16292064
TI  - Disaster management teams.
AB  - PURPOSE OF REVIEW: All disasters, regardless of cause, have similar medical and
      public health consequences. A consistent approach to disasters, based on an
      understanding of their common features and the response expertise they require,
      is becoming the accepted practice throughout the world. This strategy is called
      the mass casualty incident response. The complexity of today's disasters,
      particularly the threat of terrorism and weapons of mass destruction, has
      increased the need for multidisciplinary medical specialists as critical assets
      in disaster response. A review of the current literature emphasizes the expanding
      role of disaster management teams as an integral part of the mass casualty
      incident response. RECENT FINDINGS: The incident command system has become the
      accepted standard for all disaster response. Functional requirements, not titles,
      determine the organizational hierarchy of the Incident Command System structure.
      All disaster management teams must adhere to this structure to integrate
      successfully into the rescue effort. Increasingly, medical specialists are
      determining how best to incorporate their medical expertise into disaster
      management teams that meet the functional requirements of the incident command
      system. SUMMARY: Disaster management teams are critical to the mass casualty
      incident response given the complexity of today's disaster threats. Current
      disaster planning and response emphasizes the need for an all-hazards approach.
      Flexibility and mobility are the key assets required of all disaster management
      teams. Medical providers must respond to both these challenges if they are to be
      successful disaster team members.

PMID- 16292065
TI  - Coagulopathy in the trauma patient.
AB  - PURPOSE OF REVIEW: Homeostasis represents a delicate balance between hemostatic
      and fibrinolytic processes. This balance permits arrest of hemorrhage after mild
      injury but prevents thrombosis from occurring under normal circumstances. Trauma
      disturbs the equilibrium between hemostatic and fibrinolytic processes,
      frequently producing either a hypocoagulable state or a hypercoagulable state
      depending on the severity of injury, degree of hemorrhage, and the nature of the
      resuscitation. The purpose of this review is to describe the epidemiology and
      pathophysiology of coagulopathy after trauma and to discuss novel methods of
      treating it. RECENT FINDINGS: Published reports during the past year focus on the
      pathophysiology of coagulopathy after trauma and novel methods of treatment.
      Individual effects of hypothermia and acidosis on clotting factors and platelet
      function have been described. The effects of varying resuscitation fluids on
      coagulopathy have also been described as well as the course of coagulopathy over
      time. Recombinant factor VIIa has emerged as a popular therapy for traumatic
      coagulopathy although a prospective randomized trial has yet to be published. The
      efficacy of several new dressings for the local control of hemorrhage has been
      reported. SUMMARY: Changes in coagulation following trauma are characterized by a
      complex series of events that may result in either a hypocoagulable or a
      hypercoagulable state. Routinely analyzed coagulation parameters do not
      adequately describe this state and they are deficient for guiding its therapy.
      Several promising new agents are available for treating hemorrhage in
      coagulopathic trauma patients that should result in improved survival.

PMID- 16292066
TI  - Evidence-based ethics?

PMID- 16292067
TI  - Ethics consultation in the intensive care unit.
AB  - PURPOSE OF REVIEW: To review the medical literature for recent reports of the
      role of ethics consultations in the intensive care setting. RECENT FINDINGS:
      Ethical principles can provide important guidelines for dealing with value
      conflicts in medical treatment decisions, particularly treatment decisions to
      limit life-sustaining treatment in the intensive care unit. Until recently,
      advocates of ethics consultations have had to rely on inconclusive supporting
      data. In the past few years, however, a single-site and multi-site prospective
      randomized controlled trial of the ethics consultations offered in response to
      treatment conflicts in the intensive care unit demonstrated significant
      reductions in hospital days, hospital costs, and ventilator days in patients who
      did not survive to hospital discharge. The consultations were very well received
      by all the parties. SUMMARY: Ethics consultations seem to be useful in resolving
      conflicts that may be inappropriately prolonging nonbeneficial or unwanted
      treatments at the end of life. Further research on whether ethics consultations
      are beneficial in other settings is needed to establish the optimal scope of this
      intervention. Also, because these benefits were achieved by highly skilled and
      experienced consultants, it is not certain how successful other hospitals will be
      when adopting this intervention.

PMID- 16292068
TI  - Critical care: why there is no global bioethics.
AB  - PURPOSE OF REVIEW: The possibility of content-full, universal, bioethical norms
      is assessed. The literature brings into question a global bioethics. A salient
      moral and bioethical pluralism undermines the plausibility of imposing of uniform
      bioethical norms on critical care. Addressing the tension between the aspiration
      to a global bioethics and the presence of moral pluralism is timely, given the
      United Nations Educational, Scientific and Cultural Organization's development of
      universal, bioethical norms. The practice of critical care in the 21st century
      will be influenced by the tension between bioethical pluralism and counter
      assertions on behalf of a global bioethics. RECENT FINDINGS: A growing literature
      reflects a bioethical pluralism with significant implications for critical care.
      Much of the literature supporting pluralism is rooted in a reaction in the
      Pacific Rim against North American and Western European moral and philosophical
      commitments. These voices of moral dissent join an already salient moral
      diversity in the West regarding issues ranging from abortion to end-of-life
      decision-making, physician-assisted suicide, and euthanasia, as well as
      conflicting understandings of the bioethics of appropriate approaches to the
      allocation of scarce medical resources. This literature acknowledging bioethical
      diversity contrasts with announcements of universal bioethical norms. SUMMARY:
      Clinicians need to appreciate the sources of moral controversy that divide them
      from their patients and from their colleagues and to recognize that moral and
      economic differences may lead to different standards of care. Taking bioethical
      diversity seriously supports focusing on procedural moral approaches that allow
      peaceable collaboration in the face of substantive moral disagreement.

PMID- 16292069
TI  - Care near the end-of-life in critically ill patients: a North American
      perspective.
AB  - PURPOSE OF REVIEW: End-of-life care for critically ill patients has emerged as an
      area in which significant quality improvement is possible. In this article, we
      present a North American perspective on recent research and quality improvement
      initiatives in this field. RECENT FINDINGS: Some of the most important recent
      developments in end-of-life care in the intensive care unit concern physician
      patient-family communication. There is consensus between North American and
      European professional societies that a shared approach to decision-making by
      physicians and family members is optimal. The shared decision approach demands
      that physicians not only skillfully elicit the patient's treatment preferences
      but also effectively inform the family of the patient's clinical condition and
      prognosis. Moreover, the ultimate responsibility for end-of-life treatment
      decisions is shared between the physician and the patient or family. SUMMARY:
      This update presents a North American perspective on six topics of particular
      importance to end-of-life care in the intensive care unit: (a) The role of
      advance directives, (b) shared decision-making and the role of the family, (c)
      conflict and futility in the intensive care unit, (d) cultural aspects of end-of
      life care, (e) multidisciplinary care in the intensive care unit, and (f) future
      directions for improving end-of-life care in the intensive care unit.

PMID- 16292070
TI  - Care at the end of life in critically ill patients: the European perspective.
AB  - PURPOSE OF REVIEW: Care surrounding end-of-life has become a major topic in the
      intensive care medicine literature. Cultural and regional variations are
      associated with transatlantic debates about decisions to forego life-sustaining
      therapies and lead to recent international statements. The aim of this review is
      to provide insight into the decisions to forego life sustaining therapies and end
      of-life care in Europe. RECENT FINDINGS: Although decisions to forego life
      sustaining therapies are increasingly made in European countries, frequency and
      characteristics of end-of-life care are still heterogeneous. Moreover, even
      though many determinants of these variations have been identified, epidemiologic
      and interventional studies still provide additional information. In agreement
      with public opinions, recent European laws have emphasized the patient's
      autonomy. In real life, advance care planning is rarely used. Decisions are often
      made by caregivers (physicians and nurses) or families, these latter being less
      involved than in North America. Not only ethic divergences between physicians but
      also cultural variations account for this disparity. SUMMARY: To optimize end-of
      life care in the intensive care unit, there is an urgent need for the development
      of palliative and multidisciplinary care in Europe. Furthermore, it highlights
      the need for culturally competent care, adapted to needs and values of every
      single patient and family. In addition, a lack of communication with families and
      within the medical team, an uninformed public about end-of-life issues, and
      insufficient training of intensive care unit staff are crucial barriers to end-of
      life care development. Special awareness of professionals and innovative research
      are needed to promote a high-standard of end-of-life care in the intensive care
      unit.

PMID- 16292071
TI  - Informed consent in the intensive care unit: ensuring understanding in a complex
      environment.
AB  - PURPOSE OF REVIEW: Informed consent in the intensive care unit continues to
      receive marked attention. As greater numbers of patients enter into the intensive
      care unit with devastating illness, patients and families are faced with more
      complex medical problems and decisions regarding therapy. Furthermore, research
      investigations of critical illness add a level of complexity to informed consent
      and decision making that mandates a careful approach. RECENT FINDINGS:
      Publications in the past year evidence the potential obstacles for appropriate
      informed consent. Physicians demonstrate variability in interpretation for the
      need for informed consent and frequently lack formal training in communicating
      informed consent. Critical care researchers must communicate the goals and
      benefits of trial participation carefully, avoiding the demonstrably common
      pitfall of therapeutic misconception. Excellent consensus statements now exist to
      guide the researcher in pursuing critical care research, creating informed
      consent documentation, and recognizing the appropriate setting for waiver of
      consent. As expected, extended discussion is the most effective tool for
      improving the quality of informed consent. SUMMARY: Quality of informed consent
      for the critically ill improves as attention is paid to standardizing indications
      and formalizing training for physicians. In research, conflicts of interest
      should be recognized and used to guide the investigator's dialogue on research
      benefits and risks. Patient safety must be maintained as the primary priority;
      however, waiver of consent may be considered in situations in which the benefit
      to medical knowledge far exceeds patient risk.

PMID- 16292072
TI  - Rationing critical care medicine: recent studies and current trends.
AB  - PURPOSE OF REVIEW: This paper reviews the literature on the rationing of critical
      care resources. RECENT FINDINGS: Although much has been written about the concept
      of rationing, there have been few scientific studies as to its prevalence. A
      recent meta-analysis reviewed all previously published studies on rationing
      access to intensive care units but little is known about practices within the
      intensive care unit. Much literature in the past few years has focused on the
      growing use of critical care resources and projections for the future. Several
      authors suggest there may be a crisis in financial or personnel resources if some
      rationing does not take place. Other papers have argued that the methods of
      rationing critical care previously proposed, such as limiting the care of dying
      patients or using cost-effectiveness analysis to determine care, may not be
      effective or viewed as ethical by some. Finally, several recent papers review how
      critical care is practiced and allocated in India and Asian countries that
      already practice open rationing in their health care systems. SUMMARY: There is
      currently no published evidence that overt rationing is taking place in critical
      care medicine. There is growing evidence that in the future, the need for
      critical care may outstrip financial resources unless some form of rationing
      takes place. It is also clear from the literature that choosing how to ration
      critical care will be a difficult task.

PMID- 16292077
TI  - The development of mucosal immunity.
AB  - The development of the intestinal immune system is a complex sequence of events
      that begins in utero under various genetic influences, but continues after birth,
      being modified by factors such as bacteria, hormones and feeds. This review
      discusses what is known about the ontogeny of each aspect of the mucosal immune
      system so as to provide a better understanding of how aberrations in the system
      might lead to systemic disease.

PMID- 16292078
TI  - Gut barrier dysfunction in food allergy.
AB  - Intestinal permeability tests used in the diagnosis of allergic diseases in
      response to oral food challenge have led to the conclusion that constitutive
      defects of the intestinal barrier are not the primary cause of allergic diseases.
      However, perturbation of environmental factors (infection, stress), by increasing
      intestinal permeability and enhancing danger signals, may favour food allergy in
      susceptible individuals. The mechanisms of enhanced permeability to specific and
      bystander antigens have been delineated as well as the molecular events involved
      in the sequential phases of allergic reactions. Intestinal absorption of food
      antigens and immune responses are mutually dependent, and luminal (environmental)
      and serosal (intrinsic) factors synergize to maintain a self-perpetuating cycle
      in which antigens penetrate the mucosa and induce allergic inflammation.

PMID- 16292079
TI  - Clinical manifestations of food allergy: the old and the new.
AB  - Food allergies are increasing in incidence, and the variety of triggering
      antigens is widening. There is also an increased recognition of the breadth of
      immunologically mediated responses to dietary antigens; the area of non-IgE
      mediated food allergy is belatedly acquiring scientific respectability, aided by
      improved clinical recognition and basic scientific studies. The role of mucosal
      mast cells and eosinophils in intestinal allergic responses is now better
      recognized, and conditions such as eosinophilic oesophagitis are more prevalent
      than previously thought. However, the diagnostic difficulties of non-IgE-mediated
      allergies remain challenging.

PMID- 16292080
TI  - Gastrointestinal allergy in adults.
AB  - The prevalence of food allergy reaches 3% in the adult population. Chronic
      gastrointestinal allergy is a rare entity: 4.2% of food allergies in adults, and
      represents 3.2% of all intestinal disorders. Non-specific symptoms are the rule
      but eosinophilic gastrointestinal disorders are the subject of much interest.
      Endoscopy and biopsies of the gastrointestinal tract help the differential
      diagnoses. Food allergy is suspected from the patient's history leading to skin
      tests and laboratory tests identifying a sensitization but allergy is only
      confirmed by standardized challenges or eviction diets over a sufficiently long
      period. New types of investigations coupling oral challenges to foods to
      gastroenterological techniques should be studied further.

PMID- 16292081
TI  - Oral tolerance: lessons on treatment of food allergy.
AB  - Oral tolerance is the active non-response by the immune system to an antigen
      administered through the oral route. It is postulated that food hypersensitivity
      results from a breakdown in oral tolerance induction, and the importance of oral
      tolerance in food hypersensitivity can be traced back to classic experiments from
      1911 in which guinea pigs were protected from anaphylaxis by prior feeding of
      antigen. Host and antigenic factors play a role in determining the pathways and
      mechanisms to which a fed antigen can gain tolerance. Recent studies have
      demonstrated the potential of using oral tolerance to treat food allergies, and
      additional studies are necessary to further our understanding of mechanisms of
      oral tolerance induction.

PMID- 16292082
TI  - Management of food allergy: vitamins, fatty acids or probiotics?
AB  - The dietary approach to allergic disease in infancy is evolving from passive
      allergen avoidance to active stimulation of the immature immune system, the aim
      of which is to support the establishment of tolerance. This may include
      probiotics providing maturational signals for the gut-associated lymphoid tissue
      and by balancing the generation of pro and anti-inflammatory cytokines in
      addition to their capacity to reduce the dietary antigen load by degrading and
      modifying macromolecules. Probiotics have also been shown to reverse the
      increased intestinal permeability characteristic of children with food allergy
      and to enhance specific IgA responses frequently defective in children with food
      allergy. The promotion of gut barrier functions by probiotics also includes the
      normalization of the gut microecology, alterations in which have been
      demonstrated in allergic individuals. Dietary lipids, especially long-chain
      polyunsaturated fatty acids, regulate immune function and may modify the
      adherence of microbes in the mucosa thereby contributing to host-microbe
      interactions. The properties of specific dietary compounds in optimal
      combinations and the joint effects of nutrients can be exploited in the
      development of specific prophylactic and therapeutic interventions. To meet these
      targets, rigorous scientific effort is required to elucidate how the food matrix
      and the dietary content impacts on the complex cascade of interrelated
      immunological mechanisms in food allergy.

PMID- 16292083
TI  - An eye witness perspective of the changing patterns of food allergy.
AB  - Food allergy may affect the gastrointestinal tract of children and adults too,
      albeit less commonly. The changing clinico-pathological expression of such food
      allergy in children over a 30 year period is related, from the eye witness
      perspective of a paediatric gastroenterologist in London. Tissue diagnosis by
      biopsy, related to dietary elimination and challenge has been the basis for the
      first clinico-pathological descriptions and accurate clinical diagnosis of these
      syndromes as they affect the gastrointestinal tract. In the 1970s cow's milk
      sensitive enteropathy presenting as chronic diarrhoea and failure to thrive in
      infancy often after infective gastroenteritis, especially with enteropathogenic
      Escherichia coli, was an important problem. By the late 1990s such presentations
      had become most uncommon in developed communities but they continue to occur in
      developing communities. By contrast in more recent times, multiple food allergy
      associated with minor small intestinal enteropathy and gastro-oesophageal reflux
      in older children has become an important clinical problem in children seen in
      developed communities. Accompanying these changes has been a dramatic fall in the
      number of children with clinically severe gastroenteritis with severe dehydration
      requiring hospital admission. Furthermore, the widespread diagnostic use of
      endoscopy of the upper and lower gastrointestinal tract in children with multiple
      biopsies has expanded gastroenterological diagnosis in children. This approach
      gives information about the oesophagus and ileo-colon not available in the
      earlier studies, which largely concentrated upon small intestinal biopsies,
      obtained by Crosby capsule biopsy. So, over this 30 year period clinico
      pathological expression has altered but also the diagnostic approach has
      technically changed.

PMID- 16292084
TI  - Management of low and high-grade dysplasia in inflammatory bowel disease: the
      gastroenterologists' perspective and current practice in the United Kingdom.
AB  - BACKGROUND: Colonic dysplasia is a precursor to colorectal cancer (CRC) in
      inflammatory bowel disease (IBD). There is a risk of progression of both low
      grade dysplasia (LGD) and high-grade dysplasia (HGD) to CRC over 5 years. The
      current British Society of Gastroenterology guidelines advocate colectomy when
      possible or at least colonoscopic surveillance every 6 months. AIM: To obtain an
      overview of the gastroenterologists' perspective on various aspects of colonic
      dysplasia in IBD and to understand current management practice in the UK.
      METHODS: A national postal survey of 551 gastroenterologists listed in the
      British Society of Gastroenterology Handbook 2003. RESULTS: Some 56% of
      questionnaires were returned; 255 out of 551 completed questionnaires were
      included in the final analysis. A total of 70% considered LGD to be premalignant,
      whereas all considered HGD to be premalignant. Only 13% offered routine colectomy
      for LGD compared with 84% for HGD. More than a third felt that flat LGD might not
      have concurrent CRC, of which 95% performed surveillance colonoscopies in this
      group. A small proportion of the remaining gastroenterologists treated flat LGD
      surgically (13%), whereas 85% considered that LGD with dysplasia-associated
      lesion or mass (DALM) constituted a high risk of concurrent CRC, but only 52.5%
      offered total colectomy to this group. There was a wide variation in the
      frequency of surveillance for LGD in flat mucosa and DALM. A majority agreed that
      LGD progressed to HGD (82%) and CRC (75%). However, their perception of the risk
      of progression to either HGD or CRC over 5 years varied widely. All agreed that
      HGD may have coexistent CRC, and 98% thought it progressed to CRC. Patients were
      more likely to be treated with colectomy for flat HGD (77%) and HGD in the
      presence DALM (86%); 38% of gastroenterologists felt that over 30% of patients
      have coexistent CRC in HGD, and 10% continued to manage them conservatively.
      CONCLUSION: There are wide variations in the perceptions and management of LGD in
      IBD in the UK compared with HGD, in which there seems to be more uniform
      agreement. The need for more research in this area and a national agreement on
      management is paramount. Until this is reached gastroenterologists will remain
      open to criticism and litigation.

PMID- 16292085
TI  - Prospective evaluation of high-frequency mini-probe ultrasound colonoscopic
      imaging in ulcerative colitis: a valid tool for predicting clinical severity.
AB  - BACKGROUND: High-frequency mini-probe ultrasound imaging permits trans-mural
      cross-sectional imaging of the colorectal wall. In ulcerative colitis, prognosis
      is dependent on the severity of mucosal inflammatory change where accurate
      assessment of disease activity is required to optimize medical therapy.
      Furthermore, predicting relapse of disease using conventional endoscopic,
      histopathological and clinical criteria has not proven reliable. AIM: To evaluate
      the correlation of high-frequency mini-probe imaging with standardized measures
      of clinical, endoscopic and histopathological severity. METHODS: High-frequency
      ultrasound images were obtained from the caecum to rectum in 200 patients. Tsuga
      colorectal ultrasound criteria were then compared to the endoscopic Baron score,
      Seo activity score and Matts histopathological grade. RESULTS: For rectal
      disease, the kappa coefficient between Tsuga criteria I/II and Matts grade 1/2
      was 0.78 (95% CI, 0.67-0.89), 0.57 (95% CI, 0.46-0.68) and 0.48 (95% CI, 0.34
      0.62) for Tsuga class IIIa/b, IVa/b and Matts grade 3a/b and 4, respectively.
      Colonic imaging showed a kappa coefficient between Tsuga class I/II and Matts
      grade1/2 of 0.76 (95% CI, 0.72-0.8). Tsuga class IIIa-IIIb/IVa-IVb as compared to
      Matts grade 3a-3b/4 yielded kappa coefficients of 0.49 (95% CI, 0.43-0.55) and
      0.62 (95% CI, 0.56-0.69), respectively. In the rectum both the total wall
      thickness, mucosa and submucosa were significantly thicker in Matts grade 3b and
      4 disease as compared to Matts grade 1/2 (P < 0.02) for all parameters. A
      significant increase in colonic total wall thickness was observed between Matts
      score 4 and Tsuga grade 1-3a disease (P < 0.001). CONCLUSIONS: High-frequency
      ultrasound is a valid adjunctive 'tool' for the trans-mural assessment of the
      colorectal wall in ulcerative colitis. This technique may aid in the initial
      diagnosis, and ongoing chronic management of disease.

PMID- 16292087
TI  - Longitudinal trends of stomach cancer and esophageal cancer in Yangzhong County:
      a high-incidence rural area of China.
AB  - OBJECTIVE: This study aims to investigate the recent trends in incidence rates of
      stomach cancer and esophageal cancer in a high-incidence rural area of China.
      METHODS: All new cancer occurrences registered between 1991 and 2003 in the
      Yangzhong Cancer Registry were reviewed. Yearly age-specific and age-adjusted
      incidence rates were calculated for males and for females. Longitudinal trends of
      cancer incidence were estimated by the estimated annual percentage change method.
      RESULTS: In total 12 691 incident cancer cases were registered, with 7159 males
      (56.41%) and 5532 females (43.59%). Adjusting to the world standard population,
      the incidence rate of all cancers decreased significantly across the period 1991
      2003 from 357.02 to 283.21 per 10 person-years. For males this rate decreased
      from 447.22 to 346.72 per 10 person-years, and for females the incidence rate
      decreased from 284.36 to 225.73 per 10 person-years. The major cancers in
      Yangzhong County were stomach cancer and esophageal cancer, accounting for more
      than 70% of all cancer occurrences. During the past 13 years, the incidence rates
      of stomach cancer decreased greatly from 231.92 to 145.26 per 10 person-years in
      males and from 114.16 to 74.59 per 10 person-years in females. The estimated
      annual percentage changes of stomach cancer incidence were -2.96% [95% confidence
      interval (CI), -2.99% to -2.92%] in males and -2.86% (95% CI, -2.89% to -2.82%)
      in females. Incidence rates for esophageal cancer decreased slightly from 121.48
      to 93.84 per 10 person-years in males with an estimated annual percentage change
      of -1.39% (95% CI, -1.42% to -1.36%), and from 99.74 to 73.73 per 10 person-years
      in females at an annual change of -2.18% (95% CI, -2.22% to -2.14%). CONCLUSION:
      Findings from this study showed that, although there is a decreasing trend of
      stomach cancer and esophageal cancer in this high-incidence area, the rates
      remain high. Future effort should be directed toward identifying factors behind
      the high rates and those contributing to the decreasing trend.

PMID- 16292086
TI  - Predisposing HLA-DQ2 and HLA-DQ8 haplotypes of coeliac disease and associated
      enteropathy in microscopic colitis.
AB  - OBJECTIVE: To assess the presence of both genetic and serological markers of
      coeliac disease in patients with microscopic colitis, and whether there was
      associated enteropathy. METHODS: HLA-DQ2, HLA-DQ8, serum immunoglobulin A
      antiendomysial and immunoglobulin A-anti-tissue transglutaminase antibodies were
      investigated in 59 patients with microscopic colitis. Seventy healthy subjects
      acted as the control group. Endoscopic biopsies from the distal duodenum were
      obtained in DQ2-positive or DQ8-positive patients. Patients with histological
      changes compatible with gluten-sensitive enteropathy were started on a gluten
      free diet. RESULTS: Seventeen of 70 (24.3%) healthy controls were DQ2-positive.
      Twelve of 25 (48%) patients with lymphocytic colitis (P = 0.027 versus controls),
      and 11 of 34 (32.3%) with collagenous colitis (P = 0.38 versus controls) were DQ2
      positive. There were no differences in the frequency of DQ8-positivity. The
      coeliac serology was positive in one patient. Duodenal biopsies were performed in
      23 DQ2-positive and/or DQ8-positive patients. None had villous atrophy (Marsh III
      lesion) (0%; 95% confidence interval, 0-6.1). A Marsh type I lesion was found in
      four patients. Three of these patients were put on a gluten-free diet with
      disappearance of diarrhoea. CONCLUSIONS: The results suggest that there is an
      association of lymphocytic colitis with HLA-DQ2 genes, which might be relevant in
      the pathogenesis of this disease. The association of microscopic colitis with
      Marsh type III coeliac disease seems to be rare, making it unnecessary to
      routinely screen for coeliac disease in microscopic colitis patients.

PMID- 16292088
TI  - Evaluation of the diagnostic accuracy of gastroscopy to detect gastric tumours:
      clinicopathological features and prognosis of patients with gastric cancer missed
      on endoscopy.
AB  - OBJECTIVES: Some gastric cancers are missed during diagnostic gastroscopy, but
      data are sparse on the clinical characteristics of patients with missed gastric
      cancers and on the accuracy of gastroscopy for detecting these tumours. We
      evaluated the number, clinicopathological characteristics, and survival of
      patients with missed gastric cancers, and the sensitivity and specificity of
      gastroscopy to detect these tumours. METHODS: Data on gastric cancers detected in
      1996-2001 in a single hospital referral area were obtained from the National
      Cancer Registry. Patient files were examined to identify those who underwent
      gastroscopy less than 3.5 years before a cancer diagnosis. RESULTS: Of the 284
      gastric cancer patients, 13 (4.6%) had undergone gastroscopy in the previous 3.5
      years; their mean age was 72.4 years at the time of the first gastroscopy. The
      median delay in cancer diagnosis was 11.5 months. Histologically, all patients
      had gastric carcinoma. The sensitivity and specificity of gastroscopy for
      diagnosing gastric cancer were 0.93 and 1.00, respectively. Among the deceased
      patients, no difference was observed in the survival of cases with non-missed (n
      = 191) and missed (n = 10) carcinoma: 9.4 versus 7.3 months (P = 0.15).
      CONCLUSION: A small proportion of gastric carcinomas are missed on gastroscopy,
      causing a significant delay in diagnosis. However, the prognoses of patients with
      missed and non-missed gastric carcinoma were equally poor.

PMID- 16292089
TI  - The effect of regular and high doses of omeprazole on the intragastric acidity in
      patients with bleeding peptic ulcer treated endoscopically: a clinical trial with
      continuous intragastric pH monitoring.
AB  - OBJECTIVE: In peptic ulcer bleeding (PUB), pH level >4 is considered necessary to
      prevent dissolving of a formed fibrin clot. The effect of regular or high doses
      of omeprazole on the intragastric pH in patients with acute PUB was studied.
      METHODS: In our earlier study, after endoscopic therapy, PUB patients were
      randomized to receive a regular dose of intravenous omeprazole (20 mg; i.e. 60
      mg/3 days) or a high dose of omeprazole (80 mg bolus + 8 mg/h; i.e. 652 mg/3
      days). Of these 142 analysed and reported patients, 13 PUB patients also had
      intragastric pH monitoring for these 3 days; seven of these patients had a
      regular dose and six received a high dose of omeprazole. RESULTS: The mean 24-h
      intragastric pH (regular versus high dose) on day 1 was 4.9 +/- 1.6 versus 6.3 +/
      0.5 (P = 0.035), on day 2 was 4.9 +/- 1.8 versus 6.7 +/- 0.3 (P = 0.001), and on
      day 3 was 5.7 +/- 1.1 versus 6.7 +/- 0.5 (P = NS). The medians of the
      intragastric pH were 6 versus 6.5 (P = 0.082) on day 1, 5.8 versus 6.8 (P =
      0.001) on day 2, and 6.2 versus 6.8 (P = 0.17) on day 3. The proportion of time
      when pH <4 on day 1 was 29.2 +/- 34.1 versus 5.4 +/- 5.7% (P = NS). CONCLUSIONS:
      A regular dose of omeprazole raises the mean and median 24-h intragastric pH >4
      in patients with PUB. This reduction in the acidity together with endoscopic
      therapy is probably sufficient to maintain haemostasis. A high dose of omeprazole
      keeps the pH almost constantly >6.

PMID- 16292090
TI  - Efficacy and safety of Saccharomyces boulardii in prevention of antibiotic
      associated diarrhoea due to Helicobacterpylori eradication.
AB  - BACKGROUND AND AIM: Antibiotic-associated diarrhoea may develop during or
      following Helicobacter pylori eradication. We aimed to evaluate the efficacy and
      safety of Saccharomyces boulardii in preventing antibiotic-associated diarrhoea
      in patients receiving antibiotics for H. pylori eradication. METHODS: In a
      multicentre prospective clinical trial, patients with peptic ulcer disease or non
      ulcer dyspepsia were enrolled to receive clarithromycin, amoxicillin and
      omeprazole for H. pylori eradication for 14 days. These patients were then
      randomized to receive either S. boulardii 500 mg twice daily (treatment group) or
      no treatment (control group). The primary outcome measure was the development of
      diarrhoea during (treatment period) or within 4 weeks after treatment (follow-up
      period). RESULTS: Of the 389 patients that were enrolled, 376 completed the
      study. Within the treatment period, diarrhoea developed in 5.9% of patients in
      the treatment group and in 11.5% of patients in the control group (P = 0.049);
      and in the follow-up period, diarrhoea developed in 1.0% of patients in the
      treatment group and in 3.8% of patients in the control group (P = 0.09). Overall
      diarrhoea rates throughout the whole study period were 6.9% in the treatment
      group and 15.6% in the control group (P = 0.007). No significant difference was
      observed between the treatment and control groups in terms of adverse events.
      CONCLUSION: S. boulardii is an effective and safe treatment for prevention of
      antibiotic-associated diarrhoea when given concomitantly to patients receiving H.
      pylori eradication.

PMID- 16292091
TI  - Investigation of Helicobacter pylori infection in beta-thalassaemia major
      patients with recurrent abdominal pain.
AB  - BACKGROUND: Recurrent abdominal pain (RAP) affects many children, especially
      those affected by beta-thalassaemia major. The role of Helicobacter pylori is
      still unclear in children with RAP. OBJECTIVES: The aim of the present study was
      the comparison of beta-thalassaemia major patients and normal controls with RAP
      in H. pylori infection. The factors influencing H. pylori prevalence were also
      investigated. METHODS: A series of 50 beta-thalassaemia major cases (30 female,
      20 male; aged 6-25 years) and 50 age-matched and sex-matched controls, both
      presenting with RAP, were recruited during a period of 18 months. The study
      participants were obtained through a multistage random sampling method among
      those that met Apley's criteria. All the patients and controls had undergone
      diagnostic oesophagogastroduodenoscopy with biopsy. H. pylori infection was
      confirmed by two histopathological examinations on an endoscopy sample and a
      rapid urease test. RESULTS: H. pylori infection in thalassaemic patients was more
      common than in controls [34/50 (68%) versus 30/50 (60%)], but this higher
      frequency was not statistically significant. A clear relationship was found
      between the prevalence of H. pylori and age, duration of transfusion/chelation
      programmes, pain duration and splenectomy. In contrast, H. pylori did not
      correlate with abdominal pain characteristics, blood group, serum ferritin level
      and pathology of the upper gastrointestinal tract. The most frequent endoscopy
      abnormality was gastritis (72%). Nausea and heartburn were the leading associated
      symptoms. CONCLUSION: The high prevalence of H. pylori infection suggests that H.
      pylori should be remembered as a probable cause of RAP in beta-thalassaemia major
      patients.

PMID- 16292092
TI  - Health economic evaluation of stent or endoluminal brachytherapy as a palliative
      strategy in patients with incurable cancer of the oesophagus or gastro
      oesophageal junction: results of a randomized clinical trial.
AB  - OBJECTIVE: To relieve dysphagia is the main goal in palliative treatment of
      patients with incurable cancer of the oesophagus or the gastro-oesophageal
      junction. The aim of this prospective, randomized multicentre study was to
      compare stent placement and brachytherapy regarding health economy and clinical
      outcomes. METHODS: Patients with incurable cancer of the oesophagus or gastro
      oesophageal junction were randomized to receive a self-expandable metallic stent
      or 3 x 7 Gy brachytherapy. At clinical follow-up visits, dysphagia was scored and
      health care consumptions were recorded. Costs were based on hospital debits.
      Total lifetime healthcare consumption costs and costs for the initial treatments
      were calculated and a sensitivity analysis was conducted. RESULTS: Thirty
      patients were randomized to each treatment group. There was no difference in
      survival or complication rates between the two treatment strategies. There was a
      significant difference in the change of dysphagia scores between the time of
      inclusion and the 1-month follow-up visit, in favour of the stented group (P =
      0.03). This difference had disappeared at 3 months. Median total lifetime costs
      were 17,690 for the stented group compared with 33 171 for the brachytherapy
      group (P = 0.005). This difference was due to higher costs for the initial
      treatment (4615 versus 23 857, P < 0.0001). Sensitivity analyses showed that the
      charges for a brachytherapy session had to be reduced from 6092 to 4222 (31%) to
      make this therapeutic concept cost-competitive. CONCLUSION: Stenting is currently
      more cost-effective compared with fractionated 3 x 7 Gy brachytherapy for
      patients with incurable cancer of the oesophagus and gastro-oesophageal junction.

PMID- 16292093
TI  - The clinical course of ulcerative colitis after orthotopic liver transplantation
      for primary sclerosing cholangitis: further appraisal of immunosuppression post
      transplantation.
AB  - BACKGROUND AND AIMS: The course of ulcerative colitis (UC) following orthotopic
      liver transplantation (OLT) for primary sclerosing cholangitis (PSC) is unclear.
      We documented the nationwide experience of the course of UC, before and after OLT
      for PSC. METHODS AND RESULTS: A total of 470 liver transplants were performed for
      413 patients between 1992 and 2003, in the Scottish Liver Transplantation Unit,
      UK. Twenty-six patients had co-existing UC/PSC. Of these, data from 20 patients
      were studied over a median period of 11.9 years before OLT and 4.4 years after
      OLT; of the others, four patients required colectomy prior to OLT, one died
      within 7 days of transplant, and one developed UC after transplant. A
      significantly higher relapse rate (number of relapses/year of follow-up) was seen
      after OLT (median 1.0 versus 0.3; interquartile range, 0.10-1.42 and 0.01-0.40,
      respectively; P = 0.007). The corticosteroids requirement (number of courses/year
      of follow-up) after OLT was also significantly higher (0.40 versus 0.10;
      interquartile range, 0.51-1.13 and 0.05-0.12, respectively; P = 0.003). Twenty
      per cent of patients (4/20) became corticosteroid dependent after OLT. Thirty
      five per cent of patients (7/20) underwent colectomy after OLT: three for severe
      disease and four for neoplasia/dysplasia. Five patients (19%) developed neoplasia
      following OLT. CONCLUSION: Despite immunosuppression, UC follows a more
      aggressive clinical course after OLT and is associated with a high rate of
      neoplasia.

PMID- 16292094
TI  - Physician-patient relationship and disclosure behaviour in chronic hepatitis C in
      a group of German outpatients.
AB  - OBJECTIVES: In chronic hepatitis C infection, the doctor-patient relationship can
      be burdened for various reasons. Factors associated with the doctor-patient
      relationship and self-disclosure of hepatitis C virus (HCV) status have not so
      far been investigated systematically. The goal of the study was to examine self
      disclosure of HCV positivity, perceived stigmatization, and potential predictor
      variables in a German outpatient group. METHODS: In a cross-sectional single
      centre study, we included a volunteer sample of 103 HCV outpatients. Patient
      recruitment was between March 2003 and September 2004. Data were obtained from a
      fully standardized face-to-face interview [HCV disclosure behaviour (main
      interview variable), stigmatization, doctor-patient relationship] and
      psychometric self-assessment questionnaires [Hospital Anxiety and Depression
      Scale, German version; Symptom Checklist-90 Revised (global severity index);
      Inventory of Interpersonal Problems (total score)]. RESULTS: The overall general
      disclosure rate was 44.7% (with respect to all physicians). However, 75% stated
      revealing their positive serostatus in future physician appointments (P < 0.05).
      With respect to family/friends, disclosure rates were clearly higher (permanent
      partner, 99%; average, 76.7%). Patients' disclosure behaviour could not be
      predicted by sociodemographic variables or personality factors (binary logistic
      regression, P > 0.05). Similarly, the Hospital Anxiety and Depression Scale and
      Symptom Checklist-90 subscales were not substantially associated with HCV
      disclosure. Experiences of stigmatization (rate 38.8%) were more frequent in
      women (P = 0.014) and patients with higher depression scores (P = 0.029).
      CONCLUSIONS: There is a need for education in the field of chronic hepatitis C in
      order to improve the physician-patient relationship. HCV disclosure rates might
      thus be increased and the frequency of problematic contacts reduced. Importantly,
      the data show that physicians should explicitly ask for the patients' HCV status
      because unrequested disclosure cannot be taken for granted.

PMID- 16292095
TI  - Endoscopic pancreatic duct stenting for relief of pancreatic cancer pain.
AB  - INTRODUCTION: Little is known about the effects of endoscopic pancreatic duct
      (PD) decompression in patients with 'obstructive type' pain from pancreatic
      carcinoma. METHODS: Twenty patients with unresectable carcinoma of the pancreas,
      PD obstruction and postprandial epigastric pain were enrolled. The pain
      intensity, opioid dose and quality-of-life index were documented pre-treatment
      and at 4-weekly intervals. PD stenting was attempted in all patients. PD stent
      change was performed if biliary stents had to be changed or intense pain
      relapsed. RESULTS: Endoscopic PD drainage was successful in 19/20 patients by
      placement of a 7 F (n = 9) or 10 F (n = 10) plastic stent. Median follow-up was
      16 weeks. Two patients were alive at the end of follow-up. Eleven patients
      received gemcitabine chemotherapy. The pre-interventional pain score was 6.7 +/-
      0.9 points and decreased to 3.1 +/-1.4 points at 4 weeks (P < 0.001). It remained
      lowered significantly at 8/12 weeks and at the final visit (4.2 +/- 1.5 points, n
      = 13). The mean pre-stenting fentanyl dose was 85.5 +/- 34.7 microg/h, and it was
      decreased to 57.9 +/- 39.1 microg/h after 4 weeks (P < 0.01), 60.5 +/- 38.9
      microg/h after 8 weeks and 64.1+/-39.8 microg/h (P < 0.01 versus pre-treatment)
      after 12 weeks but increased to 82.7 +/- 41.3 microg/h (NS) at the final visit.
      The quality-of-life index improved 4 weeks after stenting (from 4.8+/-1 to 6.2+/
      1.5 points, P < 0.01) but was lowered to 5.5 +/- 2.3 points at 12 weeks (NS). The
      response was independent of stent diameter and chemotherapy. CONCLUSION: PD
      stenting achieved significant pain relief and short-term improvement of the
      quality of life in the majority of patients with PD obstruction due to pancreatic
      carcinoma.

PMID- 16292096
TI  - Ulcerative jejunoileitis and enteropathy-associated T-cell lymphoma.
AB  - Ulcerative jejunoileitis and enteropathy-associated T-cell lymphoma are rare
      conditions described in patients with refractory coeliac disease. Ulcerations
      affect the small bowel and are unrelated to drugs, ischaemia, infections or other
      known causes. We describe a female patient with an unclassified enteropathy who
      experienced several episodes of jejunoileal ulcerations. Several resections of
      the small bowel segments were necessary. The repetitive ulcerations were either
      from cytotoxic T cells, the patient developed a T-cell lymphoma, and malignant
      cells could be detected at the bottom of the ulcers, or from acid-producing cells
      in areas of gastric metaplasia. Two mechanisms might thus be responsible for the
      occurrence of repetitive ulceration, and require different treatment strategies.
      The patient is currently being treated with proton pump inhibitors, oral steroids
      and parenteral nutrition.

PMID- 16292097
TI  - An unexpected Cowden syndrome case found among members of a large familial
      adenomatous polyposis kindred.
AB  - Genetic testing is now considered the standard of care in the management of
      familial adenomatous polyposis (FAP). Non-carriers of mutations are excluded from
      endoscopic surveillance. During the systematic screening of the relatives of an
      affected member with FAP, one non-carrier of APC mutations was unexpectedly found
      with the typical Cowden syndrome phenotype. One large Algerian family with FAP
      was screened for an APC germline mutation. Moreover, we also performed a mutation
      search in the Cowden syndrome member for PTEN, BMPR1A or MADH4 (SMAD4) germline
      mutations. We identified a mutation in the APC gene that results in a truncated
      protein (Y935X) in the FAP proband, and subsequently in 12 FAP-affected members.
      Among the 12 APC mutation-negative members of this family, we found one member
      with the Cowden disease phenotype. However, the mutation analysis in the PTEN
      gene and the two other genes involved in juvenile polyposis, namely BMPR1A and
      MADH4 (SMAD4), in the Cowden syndrome patient failed to show any pathogenic
      mutation. Genetic testing is a powerful tool that can provide a definitive
      diagnosis for FAP. However, not all polyposes in the FAP family are adenomatous
      polyposes.

PMID- 16292098
TI  - Adult coeliac disease diagnosed by endoscopic biopsies in the duodenal bulb.
AB  - Multiple endoscopic biopsies in the descending duodenum are usually recognized as
      the standardized method for the evaluation of mucosal changes in coeliac disease.
      Generally, the duodenal bulb is not considered a useful site for biopsies, due to
      some difficulties in histological evaluation. A case in which the diagnosis of
      coeliac disease was possible only with the aid of biopsies in the duodenal bulb
      is reported; noteworthy, this unusual site for biopsies was strongly suggested by
      the presence of a mosaic-like endoscopic appearance. Only few cases (mainly in
      childhood) have been reported in which diagnosis was made with the aid of
      biopsies in the duodenal bulb. This occurrence suggests that performing biopsies
      only in the descending duodenum may not be sufficient in some patients, and
      raises the question of whether obtaining specimens both from the first and the
      second part of the duodenum might be a more correct and complete approach to this
      problem.

PMID- 16292099
TI  - Remission of protein-losing enteropathy after nodal lymphoma treatment in a
      patient with primary intestinal lymphangiectasia.
AB  - Primary intestinal lymphangiectasia (PIL), so-called Waldmann's disease, is an
      uncommon condition, characterized by dilated intestinal submucosal and subserosal
      lymphatics of the gastrointestinal tract. Protein-losing enteropathy is the most
      common manifestation of this supposed congenital disease. Since the initial
      description in 1961, 11 cases of lymphoma have been reported suggesting that PIL
      predisposes to lymphoma. Here, we report the first case of primary nodal location
      lymphoma during PIL with recovery of the protein-losing enteropathy after its
      treatment by radiochemotherapy.

PMID- 16292100
TI  - Spontaneous regression of peritoneal carcinomatosis from a rectal cancer.
AB  - Spontaneous regression of adult solid tumours is rare. Here, we present the case
      of a 51-year-old man who underwent a curative resection for an adenocarcinoma of
      the rectum in 1989. He remained well until 12 months after surgery when he
      developed a large-fixed mass proximal to the anastomosis, which was treated with
      radiotherapy but did not respond. Shortly after, he presented with intestinal
      obstruction caused by extensive intraperitoneal metastases. At laparotomy, a
      palliative entero-enterostomy and ileostomy were performed. Biopsies from the
      peritoneal lesions showed features typical of metastatic adenocarcinoma. The
      patient did not receive any additional therapy. However, his condition continued
      to improve; he remains disease free and well at present (May 2005). A review of
      the literature revealed two cases of spontaneous regression of peritoneal
      carcinomatosis secondary to a rectal cancer; we report the third case and discuss
      some of the reasons potentially responsible for the regression.

PMID- 16292101
TI  - E-cadherin mutation-associated diffuse gastric adenocarcinoma: penetrance and non
      penetrance.
AB  - According to the published medical literature to date, prophylactic gastrectomy
      undertaken in the context of carriage of a germline truncating E-cadherin
      mutation and an appropriate positive family history will lead to the discovery of
      occult foci of adenocarcinoma in all gastrectomy specimens. We describe the first
      published case of a patient whose prophylactic gastrectomy in this setting failed
      to reveal any dysplastic or malignant foci. Furthermore the patient's nephew, who
      was found to carry an identical E-cadherin mutation on family screening and also
      underwent prophylactic gastrectomy, was shown to have multi-focal diffuse
      adenocarcinoma after analysis of the gastrectomy specimen. Both patients were
      also found to have penetrant genetic haemochromatosis. Within this case, we
      discuss the clinical manifestations and penetrance of germline E-cadherin
      mutations and the difficult decisions facing both clinicians and families with
      this mutation. We also speculate on how these patients' undiagnosed genetic
      haemochromatosis may have influenced the pathology encountered.

PMID- 16292102
TI  - Acute mesenteric infarction: an important cause of abdominal pain in ulcerative
      colitis.
AB  - We present four cases of acute mesenteric infarction in patients with active
      ulcerative colitis: one presenting prior to the diagnosis of ulcerative colitis,
      two at the time of diagnosis, and one many years after the diagnosis had been
      made. Intestinal ischaemia is an important part of the differential diagnosis in
      patients with ulcerative colitis presenting with abdominal pain. Conversely, in
      patients presenting with bloody diarrhoea after mesenteric ischaemia, ulcerative
      colitis should be considered.

PMID- 16292104
TI  - Inactive hepatitis B virus carriers: a favourable clinical condition.

PMID- 16292103
TI  - Idiopathic gastric acid hypersecretion.

PMID- 16292105
TI  - Orlistat (Xenical)-induced subacute liver failure.

PMID- 16292106
TI  - The use of interferon-alpha in a small cohort of patients with a type of
      idiopathic pulmonary fibrosis, probably post-cryoglobulinaemia, hepatitis C virus
      related.

PMID- 16292111
TI  - Priapism associated with oxcarbazepine, aripiprazole, and lithium.

PMID- 16292112
TI  - Methylphenidate transdermal system.

PMID- 16292113
TI  - Ignition sequence: on mentorship.

PMID- 16292114
TI  - Methods for addressing missing data in psychiatric and developmental research.
AB  - OBJECTIVE: First, to provide information about best practices in handling missing
      data so that readers can judge the quality of research studies. Second, to
      provide more detailed information about missing data analysis techniques and
      software on the Journal's Web site at www.jaacap.com. METHOD: We focus our review
      of techniques on those that are based on the "Missing at Random" assumption and
      are either extremely popular because of their convenience or that are harder to
      employ but yield more precise inferences. RESULTS: The literature regarding
      missing data indicates that deletion of observations with missing data can yield
      biased findings. Other popular methods for handling missing data, notably
      replacing missing values with means, can lead to confidence intervals that are
      too narrow as well as false identifications of significant differences (type I
      statistical errors). Methods such as multiple imputation and direct maximum
      likelihood estimation are often superior to deleting observations and other
      popular methods for handling missing data problems. CONCLUSIONS: Psychiatric and
      developmental researchers should consider using multiple imputation and direct
      maximum likelihood estimation rather than deleting observations with missing
      values.

PMID- 16292115
TI  - Toward evidence-based treatment: child-parent psychotherapy with preschoolers
      exposed to marital violence.
AB  - OBJECTIVE: Treatment outcome for preschool-age children exposed to marital
      violence was assessed, comparing the efficacy of Child-Parent Psychotherapy (CPP)
      with case management plus treatment as usual in the community. METHOD: Seventy
      five multiethnic preschool mother dyads from diverse socioeconomic backgrounds
      were randomly assigned to (1) CPP or (2) case management plus community referral
      for individual treatment. CPP consisted of weekly parent-child sessions for 1
      year monitored for integrity with the use of a treatment manual and intensive
      training and supervision. Parents completed the Child Behavior Checklist and
      participated in the Structured Clinical Interview for DC:0-3 to assess children's
      emotional and behavioral problems and posttraumatic stress disorder (PTSD)
      symptoms. Mothers completed the Symptom Checklist-90 and the Clinician
      Administered PTSD Scale interview to assess their general psychiatric and PTSD
      symptoms. RESULTS: Repeated-measures analysis of variance demonstrated the
      efficacy of CPP with significant group x time interactions on children's total
      behavior problems, traumatic stress symptoms, and diagnostic status, and mothers'
      avoidance symptoms and trends toward significant group x time interactions on
      mothers' PTSD symptoms and general distress. CONCLUSIONS: The findings provide
      evidence of the efficacy of CPP with this population and highlight the importance
      of a relationship focus in the treatment of traumatized preschoolers.

PMID- 16292116
TI  - Assessment of depression in medically ill children presenting to pediatric
      specialty clinics.
AB  - OBJECTIVE: Self-report measures of depression may be inaccurate when applied to
      medically ill children because of the overlap between medical and psychiatric
      symptoms. The American Academy of Pediatrics endorses the use of self-reports as
      diagnostic aids (used in patients who are suspected of having an emotional
      problem by their pediatricians). This approach has not been validated. We
      evaluated the diagnostic accuracy of the Children's Depression Inventory (CDI) in
      medically ill children who were referred for evaluation by their pediatricians.
      METHOD: The evaluation included the CDI and a best estimate diagnostic procedure
      that incorporated results from semistructured and other interviews. Evaluators
      were not aware of the CDI scores when making a diagnostic determination. RESULTS:
      One hundred twenty-five patients, 8-19 years old, were referred between September
      2000 and May 2003. Eighty-one completed the diagnostic procedure. The CDI summary
      score performed well in identifying best estimate depressive disorder
      determinations in this cohort. A cutoff of 11 and above correctly identified 80%
      of cases, with a specificity of 70%. DISCUSSION: A self-report measure of
      depression (CDI) could be used as a diagnostic aid in medically ill children who
      are suspected of having an emotional problem by their pediatricians. This finding
      supports the "two-tier" depression screening approach endorsed by the American
      Academy of Pediatrics for use in pediatricians' offices.

PMID- 16292117
TI  - Pilot study: fluvoxamine treatment for depression and anxiety disorders in
      children and adolescents with cancer.
AB  - OBJECTIVE: To evaluate the safety, tolerability, and benefit of fluvoxamine for
      the treatment of major depressive disorder or anxiety disorders in children and
      adolescents with cancer. METHOD: The study was conducted from 2001 to 2004 at a
      pediatric hematology-oncology center. Fifteen children and adolescents with
      cancer were treated with fluvoxamine 100 mg/day in an open prospective 8-week
      trial. Safety and tolerability were evaluated at baseline and at weeks 4 and 8 by
      blood tests and the Side Effects Checklist. Clinical benefit was assessed with
      the Clinical Global Impressions-Improvement, the Children's Depression Rating
      Scale-Revised, and the Pediatric Anxiety Rating Scale. RESULTS: Fluvoxamine was
      well tolerated by all subjects. Psychiatric symptoms improved significantly.
      CONCLUSIONS: In this open trial, fluvoxamine appeared to be well tolerated and
      was associated with a promising reduction in the depression and anxiety symptoms
      of pediatric patients with cancer.

PMID- 16292118
TI  - Fluoxetine for the treatment of childhood anxiety disorders: open-label, long
      term extension to a controlled trial.
AB  - OBJECTIVE: To assess the efficacy of fluoxetine for the long-term treatment of
      children and adolescents with anxiety disorders, including generalized anxiety
      disorder, separation anxiety disorder, and/or social phobia. METHOD: Children and
      adolescents (7-17 years old) with anxiety disorders were studied in open
      treatment for 1 year after they completed a randomized, controlled trial (RCT)
      comparing fluoxetine and placebo. The follow-up phase assessments included
      clinician, parent, and child ratings with measures of global severity, global
      improvement, and anxiety symptoms. RESULTS: Subjects taking fluoxetine (n = 42)
      were compared with those taking no medication (n = 10) during follow-up on
      anxiety changes from the end of the RCT through the follow-up period. Statistical
      models included RCT assignment and follow-up psychological treatment. Excluded
      subjects took other medications (n = 4) or did not complete follow-up (n = 18).
      Compared with subjects taking no medication, subjects taking fluoxetine showed
      significantly superior follow-up outcomes on most measures, including clinician,
      parent, and child ratings. CONCLUSIONS: The results suggest that fluoxetine is
      clinically effective for the maintenance treatment of anxiety disorders in
      children and adolescents. A major limitation, however, was the lack of RCT
      methodology in the follow-up phase. RCTs are needed to determine the long-term
      risks and benefits of fluoxetine for this group.

PMID- 16292119
TI  - Case study: psychiatric misdiagnosis of non-24-hours sleep-wake schedule disorder
      resolved by melatonin.
AB  - This case study describes a 14-year-old male suffering from significant academic
      and personal difficulties, who has been diagnosed with depression, schizotypal
      personality disorder, and learning disabilities. Because of excessive sleepiness,
      assessment for a potential sleep disorder was performed. An overnight
      polysomnographic study revealed no primary sleep disorders. Wrist actigraphy
      revealed a non-24-hour sleep-wake pattern. Delay in temperature rhythm and
      dissociation with melatonin rhythms were also noted. Treatment with oral
      melatonin restored normal sleep-wake schedule. In a follow-up psychiatric
      evaluation, none of the above diagnoses were present. Greater awareness of sleep
      disorders may prevent psychiatric misdiagnosis of treatable sleep-wake schedule
      disorders.

PMID- 16292120
TI  - Predicting posttraumatic stress symptoms in children after road traffic
      accidents.
AB  - OBJECTIVE: To prospectively assess the prevalence, course, and predictors of
      posttraumatic stress symptoms (PTSSs) in children after road traffic accidents
      (RTAs). METHOD: Sixty-eight children (6.5-14.5 years old) were interviewed 4-6
      weeks and 12 months after an RTA with the Child PTSD Reaction Index (response
      rate 58.6%). Their mothers (n = 60) and fathers (n = 53) were assessed with the
      Posttraumatic Diagnostic Scale. RESULTS: The prevalence of moderate to severe
      PTSSs in children was 16.2% at 4-6 weeks, and 17.6% at 12 months. Mean PTSS
      scores did not decrease between the two assessments. Five children showed a
      delayed onset of PTSSs. Twelve mothers (20%) and six fathers (11.3%) met criteria
      for posttraumatic stress disorder (PTSD) at 4 to 6 weeks. At 12 months, three
      mothers (5.7%) and no fathers met diagnostic criteria. Child PTSSs at 12 months
      was significantly predicted by PTSS at 4-6 weeks and by severity of father's
      PTSD. Age, sex, injury severity, threat appraisal, and maternal PTSD did not
      significantly contribute to child PTSSs at follow-up. CONCLUSIONS: There is a
      need for careful psychological assessment of children and their parents after an
      RTA. The possibility of delayed onset of PTSSs implies a monitoring beyond the
      first weeks after the accident. The impact of fathers' PTSD on child PTSSs
      suggests that fathers ought to be actively involved in family-based prevention
      and treatment interventions of child PTSSs after RTAs.

PMID- 16292121
TI  - Longitudinal follow-up of adolescents with late-onset antisocial behavior: a
      pathological yet overlooked group.
AB  - OBJECTIVE: Antisocial behavior that begins in mid- to late adolescence does not
      fit into commonly accepted taxonomies of antisocial behavior, yet it clearly
      exists. This study examined how this course of antisocial behavior compares with
      persisting (beginning by early adolescence and continuing through late
      adolescence) and desisting (stopping by mid-adolescence) antisocial behavior in
      terms of risk for later substance dependence and background risk factors (gender,
      IQ, socioeconomic status, parental antisocial behavior, and parental divorce).
      METHOD: A population-based sample of twins from the Minnesota Twin Family Study,
      evaluated at ages 17 and 20, was used. RESULTS: The results indicated that youths
      with late onsets were similar to those with persisting antisocial behavior and
      that both groups were at higher risk of later nicotine, alcohol, and cannabis
      dependence than controls; both also had similarly high levels of background risk
      factors. The late-onset group included a significant overrepresentation of
      females, whereas the persisting and desisting groups included more males.
      CONCLUSIONS: Late-onset antisocial behavior has many of the same negative
      correlates of persisting antisocial behavior but includes significantly more
      females. Although they are excluded from the diagnosis of antisocial personality
      disorder, these youths have clinically significant problems similar to those with
      this diagnosis.

PMID- 16292122
TI  - Help-seeking for child psychopathology: pathways to informal and professional
      services in the Netherlands.
AB  - OBJECTIVE: To devise and test a model describing the process of help-seeking for
      child psychopathology in professional and informal service settings. METHOD:
      Using structural equation modeling, associations between several help-seeking
      stages, and the influence of child, family, and context characteristics on these
      stages were investigated in 246 Dutch children (4-11 years old) between April
      2000 and July 2002. Children were selected for having emotional or behavioral
      problems from a representative general practice sample; 68% of the selected
      children participated. RESULTS: School personnel played an important role in the
      process of help-seeking for child psychopathology, in both detecting service need
      and the provision of and the referral for help. Although Dutch general
      practitioners are supposed to be gatekeepers of mental health care, their role in
      help-seeking for child psychopathology was limited. Various family
      characteristics were shown to influence service need and informal or professional
      help-seeking. The influence of child characteristics on the help-seeking process
      was limited. CONCLUSIONS: Educating parents about child psychopathology and the
      availability and accessibility of care, improving general practitioners' skills
      in detecting child psychopathology, and direct contact of mental health
      professionals with general practitioners and schools may enhance access to care
      for children in need.

PMID- 16292123
TI  - Brain magnetic resonance spectroscopy in Tourette's disorder.
AB  - OBJECTIVE: Although abnormalities of neural circuits involving the cortex,
      striatum, and thalamus are hypothesized to underlie Tourette's disorder, the
      neuronal abnormalities within components of these circuits are unknown. The
      purpose of this study was to examine the cellular neurochemistry within these
      circuits in Tourette's disorder using proton magnetic resonance spectroscopy, a
      method that has not previously been used in neurobiological investigations of the
      disorder. METHOD: Proton magnetic resonance spectroscopic imaging examinations
      were conducted in 25 males with Tourette's disorder (age 10.9 +/- 2.0 years) and
      32 male comparison subjects (age 11.5 +/- 2.7 years). Spectra from frontal
      cortex, caudate nucleus, putamen, and thalamus were analyzed, and N
      acetylaspartate, creatine, choline, myoinositol, and glutamate + glutamine were
      quantified and compared between the groups. RESULTS: Patients with Tourette's
      disorder demonstrated a reduction in N-acetylaspartate and choline in the left
      putamen, along with reduced levels of creatine bilaterally in the putamen. In the
      frontal cortex, patients had significantly lower concentrations of N
      acetylaspartate bilaterally, lower levels of creatine on the right side, and
      reduced myoinositol on the left side. CONCLUSIONS: The results of this study
      suggest compromised neuronal integrity and deficits in density of neuronal and
      nonneuronal cells in components of the neural circuits implicated in Tourette's
      disorder.

PMID- 16292124
TI  - Circles inside squares: a graphic organizer to focus diagnostic formulations.

PMID- 16292125
TI  - Implementing evidence-based treatments in organizations.

PMID- 16292128
TI  - Finally, consensus!

PMID- 16292129
TI  - Use of analgesia and sedation for intubation in the neonatal intensive care unit.

PMID- 16292130
TI  - Preventing adverse perinatal outcomes through effective communication: lessons
      learned.

PMID- 16292131
TI  - Free radicals in perinatal and neonatal care, part 1: the basics.

PMID- 16292132
TI  - The physical, psychological, and social implications of caring for the pregnant
      patient and newborn with cystic fibrosis.
AB  - Cystic fibrosis (CF) involves the exocrine glands and epithelial tissues of the
      pancreas, sweat glands, and mucus glands in the respiratory, digestive, and
      reproductive tracts. Significant pulmonary disease, poor nutritional status, and
      pulmonary hypertension are results of chronic infections. When the woman with CF
      becomes pregnant, her body may find it difficult to adjust to the normal
      physiological changes of pregnancy, with the pulmonary, cardiovascular, and
      nutritional status being particularly stressed. Both the mother and the fetus are
      at a significant risk for increased morbidity and mortality. The woman whose life
      and pregnancy are compromised by CF and/or the newborn who is diagnosed with CF
      offer the nurse an extremely challenging situation--one in which physical and
      psychological care are proportional in importance. As part of the healthcare
      team, which includes a perinatologist, a pulmonary medicine specialist, a
      neonatologist, an anesthesiologist, a geneticist, a dietitian, a respiratory
      therapist, a social worker, an ethicist, and perhaps a clergyman, the nurse helps
      to coordinate and carry out the care needed for a successful outcome.

PMID- 16292133
TI  - Acute pulmonary edema in pregnancy.
AB  - Pulmonary edema is a secondary disease process characterized by an excess
      accumulation of fluid in the pulmonary interstitial and alveolar spaces,
      preventing adequate diffusion of both oxygen and carbon dioxide. The excess fluid
      accumulation interferes with maternal oxygenation and, if not identified and
      corrected, can lead to maternal and fetal hypoxemia. The purpose of this article
      is to review principles of oxygen transport and the pathophysiology, diagnosis,
      management, and nursing implications of acute pulmonary edema in pregnancy.

PMID- 16292134
TI  - Severe acute respiratory syndrome: implications for perinatal and neonatal
      nurses.
AB  - Severe acute respiratory syndrome (SARS) is an emerging infection that causes a
      potentially fatal respiratory disease. Although the SARS outbreak lasted less
      than 1 year, it resulted in significant morbidity and mortality and impacted
      nursing practices. A literature review was conducted. Only English language
      research articles in peer-reviewed journals, national organization publications,
      and book chapters were utilized. Data from 37 relevant articles were extracted,
      analyzed, and summarized. SARS' clinical description is presented, including its
      common signs/symptoms, diagnosis, and treatment. Recommended isolation practices
      for labor and delivery and proper procedures for donning, using, and doffing
      personal protective equipment are provided. Potential maternal outcomes include
      spontaneous miscarriage during the first trimester, preterm birth, emergency
      cesarean section, renal failure, secondary bacterial pneumonia, sepsis, adult
      respiratory distress syndrome, disseminated intravascular coagulation, surgical
      site infection, and maternal death. There have been no documented cases of
      vertical transmission; passive immunity is suspected on the basis of the presence
      of antibodies in some maternal body fluids. Potential neonatal outcomes include
      complications related to premature birth, intrauterine growth restriction,
      respiratory distress syndrome, and severe gastrointestinal manifestations. It is
      not known if or when SARS will reemerge, but perinatal and neonatal nurses should
      become familiar with its clinical description and proper infection control
      procedures to halt potential outbreaks.

PMID- 16292137
TI  - Neonatal lung remodeling: structural, inflammatory, and ventilator-induced
      injury.
AB  - The developing lung is subject to events, both prenatal and postnatal, that alter
      the normal developmental process. The degree of insult or injury affects how the
      lung functions at birth and then responds to the insult throughout childhood. In
      this article, only 3 of the influences are examined: structural, inflammatory,
      and mechanical. It is recognized that there is a plethora of other factors that
      influence lung remodeling.

PMID- 16292136
TI  - Effects of fetal hemoglobin on accurate measurements of oxygen saturation in
      neonates.
AB  - PURPOSE: To examine the accuracy of oxygen saturation (So(2)) in relation to
      blood oxyhemoglobin (Hbo(2)) measurements with the effects of fetal hemoglobin
      (HbF) determined and their oxyhemoglobin dissociation curves. METHOD: Twenty
      neonates with gestational ages ranging from 25 to 34 weeks, who had umbilical
      arterial or venous lines inserted, were investigated. Analyses were performed
      with 169 arterial and 41 venous blood samples from these infants by employing HbF
      and HbA-mode (as controls) blood analyses, using a hemoximeter. RESULTS: Without
      adjusting the effects of HbF when using HbA-mode analyses, mean So(2)
      measurements were elevated for 5% (+/-1.38) compared with the results of HbF-mode
      analyses, with 3.5% elevated HbCO levels for the total blood samples. With left
      shifted oxyhemoglobin dissociation curves in neonates, for the critical values of
      oxygen tension values between 50 and 75 mm Hg, arterial Hbo(2) ranged from 94% to
      96%, Sao(2) from 97% to 98%, and Spo(2) from 96% to 97% (compared to 85%-94% in
      healthy adults). CONCLUSIONS: The left-shifted oxyhemoglobin curves warrant the
      importance of accurate measurements of oxygenation status for neonates. Fetal
      hemoglobin determination is essential for accurate So(2) measurements and the
      assessment of proper oxygenation status in neonates.

PMID- 16292139
TI  - Room air resuscitation versus oxygen resuscitation in the delivery room.
AB  - The use of 100% oxygen for delivery room resuscitation is currently the
      recommended standard of the American Academy of Pediatrics and the Neonatal
      Resuscitation Program. However, there is mounting evidence from animal and human
      studies suggesting that resuscitation with room air (RA, 21% oxygen), including
      positive pressure ventilation with bag and face mask, may be as effective as that
      with 100% oxygen, and that the use of 100% oxygen may pose a risk of adverse
      physiologic sequelae. Resuscitation with RA has been demonstrated to result in
      faster recovery and improved neonatal mortality in comparison to 100% oxygen
      resuscitation. In addition, studies of normal oxygen saturation immediately after
      birth suggest delivery room personnel may be rushing to high saturation
      unnecessarily. The question for perinatal medical and nursing personnel involved
      in newborn resuscitation in the delivery room is whether the use of RA reduces
      the possible adverse effects of 100% oxygen, including delay in short-term
      stabilization, death, neurological disability, and possible secondary oxygen free
      radical injury. A systematic synopsis of both animal studies and human studies
      involving the advantages, disadvantages, possible risks, and short- and long-term
      effects of these 2 methods of resuscitation is presented.

PMID- 16292141
TI  - Using assessments to stifle rumors.

PMID- 16292142
TI  - Clinical reasoning: turning your students into clinical detectives.

PMID- 16292144
TI  - A student and RN partnered clinical experience.

PMID- 16292145
TI  - Dedicated online virtual reference instruction.
AB  - To facilitate nursing students' information literacy skills and enhance
      traditional library user services, academic librarians have developed synchronous
      (real-time) online virtual reference instruction in nursing research classes. The
      authors discuss collaborative efforts of nursing and library faculty in planning,
      implementing, and evaluating a discipline-specific virtual reference pilot
      program.

PMID- 16292146
TI  - Scoring rewards in nursing education with games.
AB  - Create a spark in teaching and learning with an educational game. Try borrowing
      from a well-recognized game for use in class. The authors discuss advantages and
      disadvantages of games and questions to ask when selecting a game. A game
      laboratory that included 4 popular game show formats is described. Pretest to
      posttest scores and surveys show that students found the game laboratory
      educational, fun, and refreshing.

PMID- 16292147
TI  - Successful enculturation: strategies for retaining newly hired nursing faculty.
AB  - Although the nursing faculty shortage negatively impacts student enrollment
      figures, it also facilitates career mobility of nursing faculty. To retain
      qualified faculty, nursing programs need to implement supportive programs that
      facilitate successful enculturation of the newly hired faculty member. The
      authors propose a series of supportive activities aimed at enculturation and
      subsequent retention of newly hired nursing faculty.

PMID- 16292148
TI  - A worksheet for critiquing quantitative nursing research.
AB  - Teaching an introductory course in research methods and critique to baccalaureate
      nursing students can be challenging for both students and instructor. One of the
      difficulties is teaching students to critique research while simultaneously
      learning basic terminology and research processes. A critique worksheet was
      developed to help students extract complex information from a research report for
      analysis and critique.

PMID- 16292149
TI  - Are you in control of the method or is the method in control of you?
AB  - The starting point for this article is the concept that there is a risk in
      slavishly adhering to one particular method in nursing education. With this
      approach in mind, the aim was to examine the use of an educational model with
      drama in relation to Gadamer's idea of method, as well as to discuss the
      conditions for lifeworld dialogues in learning encounters.

PMID- 16292150
TI  - Capturing a vision for nursing: undergraduate nursing students in alternative
      clinical settings.
AB  - An urgent need to secure additional community health placements provided initial
      motivation to use alternate clinical settings. Subsequent student requests for
      placement in these settings, rather than the traditional community settings, drew
      attention to the sites' unique and far-reaching benefits. Presenting the findings
      of a qualitative study, the authors discuss the perspectives of students,
      instructors, and RNs regarding their experiences in these alternative clinical
      settings and provide recommendations for the use of alternative settings in
      nursing education.

PMID- 16292151
TI  - Clinical partner model: benefits for education and service.
AB  - A college of nursing and a teaching hospital partnered to meet the clinical
      educational needs of nursing students and the registered nurse staff retention
      needs of the hospital. The authors describe the process used to establish the
      partnership and outline the implementation and evaluation of the collaborative
      Clinical Partner Model.

PMID- 16292153
TI  - [Functional chest imaging].

PMID- 16292154
TI  - [Long-term prognosis of hydatid lung cyst treated by video-assisted thoracic
      surgery].
AB  - With the advent of mini-invasive surgery, video-assisted thoracic surgery (VATS)
      is a good means of diagnosis and therapeutic in thoracic surgery. We report 14
      cases of hydatid cyst of the lung treated by VATS. Outcome as uneventful.

PMID- 16292155
TI  - [Guidelines for medical follow-up of adult and adolescent asthma patients. Full
      text].

PMID- 16292156
TI  - [Guidelines for medical follow-up of adult and adolescent asthma patients.
      Synopsis].

PMID- 16292157
TI  - [Hydatid cyst: another unusual localization].
AB  - We report a case of a 39-year-old woman who presented a right basicervical
      tumefaction. The chest X rays show a right cervicomediastinal opacity.
      Ultrasonography and computed tomography failed to describe the nature of the
      opacity. Because of the strong suspicion of neoplasm or a tuberculosis abscess, a
      needle aspiration of the cervical mass was performed and surprisingly revealed
      the presence of a cyst membrane allowing surgical resection. CONCLUSION: Hydatid
      disease is a likely diagnosis in endemic areas in patients presenting a cystic
      mediastinal opacity of unknown orign.

PMID- 16292159
TI  - [Pleural effusion revealing multiple myeloma].
AB  - Pleural effusion is rarely observed in multiple myeloma, its frequence is
      estimated at 6%, and its myelomatous origin occurs in only 1% of the cases. It is
      exceptionally the first sign of multiple myeloma. We report two cases of IgA and
      IgG multiple myeloma revealed by pleural effusion. The first case was a 61-year
      old woman who developed pleural effusion with a bone endobronchial and
      pericardial location of multiple myeloma; the second case was a 65-year-old man
      who had isolated pleural effusion. These pleural effusions were found to be
      caused by myeloma and were verified by the presence of the same monoclonal
      immunoglobulin in both plasma and pleural liquid. Atypical plasma cells were
      found in the pleural fluid.

PMID- 16292160
TI  - [Unusual presentation of pulmonary alveolar proteinosis].
AB  - Pulmonary alveolar proteinosis is a rare disease characterized by the
      accumulation of granular lipoproteinaceous material within the alveoli; the
      interstitium is preserved. We report the case of a 27-year-old patient
      hospitalized for exploration of asymptomatic bilateral interstitial syndrome.
      Neither the radiographic signs nor the aspect of bronchoalveolar lavage was
      typical. The diagnosis was confirmed by pathology examination of surgical lung
      biopsy specimen which revealed lesions of interstitial fibrosis and cholesterol
      granulomas in association with pulmonary alveolar proteinosis. Since there was no
      functional deterioration, therapeutic abstention was decided.

PMID- 16292158
TI  - [Mediastinal paraganglioma with pleural metastasis. A case report].
AB  - Paraganglioma is rare tumor arising from chromaffine cells. We report a 39-year
      old man who was diagnosed with anterior mediastinal paraganglioma. Computed
      tomography (CT) revealed a solid mass in the anterior mediastinum. Surgical
      biopsies obtained by sternotomy confirmed histologic and immunohistochemical
      features of paraganglioma. Surgical removal of this vascularized and invasive
      tumor was not possible to. External radiotherapy was performed. Three years
      later, the patient developed chest pain. CT findings showed right nodular pleural
      masses. Transparietal biopsy confirmed the same pathological aspect of
      paraganglioma. Chemotherapy was proposed without significant response. This
      observation confirmed the rare course of paraganglioma to pleural metastases.
      Treatment of paraganglioma is mainly surgery if the mass is resectable.

PMID- 16292161
TI  - [Exercise-induced dyspnea and hilar enlargement].
AB  - We report the case of a 46-year-old man with an uneventful history who was
      hospitalized for suspected pulmonary embolism. The chest x-ray did not reveal any
      parenchymatous anomaly but disclosed pseudo-tumoral enlargement of the pulmonary
      arteries. There was no right ventricular overload at cardiac echography and the
      pulmonary arterial pressure was normal. Helicoidal angioscan demonstrated
      aneurismal dilatation of the both pulmonary arteries, complicated by a thrombus
      on the right. Outcome was favorable with anticoagulation. After ruling out
      acquired aneurysm, the diagnosis retained was idiopathic aneurysm of the
      pulmonary arteries.

PMID- 16292162
TI  - [Malignant mesothelioma of the pleura revealed by bilateral spontaneous
      pneumothorax].

PMID- 16292165
TI  - [Oligodendrogliomas: historical background of classifications].
AB  - The story of the classifications for gliomas is related to the development of the
      techniques used for cytological and histological examination of brain parenchyma.
      After a review of these techniques and the progressive discovery of the central
      nervous system cell types, the main classifications are presented. The first
      classification is due to Bailey and Cushing in 1926. It was based on
      histoembryogenetic theory. Then Kernohan introduced, in 1938, the concept of
      anaplasia. The WHO classification was published in 1979, then revised in 1993 and
      2000. It took into account some data from both previous systems and introduced
      gradually the notion of histological criteria of malignancy. More recently;
      molecular genetics data and clinical evolution were retained. The Sainte-Anne
      classification for oligodendrogliomas is based on both histological and imaging
      data. It includes the notion of spatial histological structure of
      oligodendrogliomas. Contrast enhancement is closely related to
      endotheliocapillary hyperplasia. Gliomas classifications are changing and
      confusions can be made because of lack of reproductibility and misinterpretations
      of samples.

PMID- 16292167
TI  - [Criteria of diagnosis and grading of oligodendrogliomas or oligo-astrocytomas
      according to the WHO and Sainte-Anne classifications].
AB  - Two main classification systems are used in France for the histological typing
      and grading of oligodendrogliomas: the WHO and Sainte-Anne Hospital (SA)
      classifications. According to the WHO, the typing of diffuse gliomas is based on
      the predominant cell type, oligodendroglial versus astrocytic. In contrast, the
      SA classification is based on the distinction of two patterns of tumor growth,
      solid tumor tissue versus isolated tumor cells and also relies on imaging and
      clinical features. According to this approach, the SA classification includes in
      the category of oligodendrogliomas, the fibrillary or gemistocytic diffuse
      astrocytomas (WHO grade II) as well as a substantial proportion of astrocytomas
      WHO grade III, 2) the WHO uses multiple histological criteria for the grading of
      oligodendrogliomas (grade II versus grade III), including the degree of
      differentiation, cellular atypia, mitotic activity and necrosis. In contrast, the
      SA grading of these tumors (grade A versus B) only uses two criteria: the
      presence or absence of endothelial hyperplasia, and the presence or absence of
      contrast enhancement. This last criterion allows overcoming the problems related
      to the representativeness of surgical samples. Difficulties and discrepancies
      regarding the diagnosis of oligodendrogliomas are in part due to the lack of
      immunomarker for the identification of tumoral oligodendrocytes. The potential
      interest of new markers of oligodendroglial precursors for the diagnosis of these
      tumors will further be discussed.

PMID- 16292166
TI  - [Histology and oligodendrogenesis of glial cells].
AB  - Oligodendrogenesis is a complex and dynamic phenomenon. Knowledge of the
      underlying molecular control mechanisms advances steadily, especially in rodents.
      While the parallelism with human oligodendrogenesis is not fully established, the
      main characteristics are recognized. Neuroepithelial cells of the neural tube
      participate in both gliogenesis and neurogenesis. Oligodendrogenesis begins after
      neurogenesis and stops after birth. It is a focal phenomenon under the control of
      specific morphogenic proteins, and can generate precursors which are able to
      proliferate and migrate in the same time. Five steps of oligodendrogliogenesis
      follow one another acquiring and loosing proteinic markers. They lead to
      intricated maturation steps for generating myelinizing oligodendrocytes, NG2
      cells and precursors of quiescient adult oligodendrocytes.

PMID- 16292168
TI  - [Reappraisal of the Sainte-Anne Hospital classification of oligodendrogliomas in
      view of retrospective studies].
AB  - PURPOSE: Definition of homogeneous tumor groups of oligodendrogliomas or oligo
      astrocytomas is a basic condition for an adequate evaluation and comparison of
      the results of treatments in patients from various institutions. However,
      increasing discordances are observed in the histological diagnosis of these
      tumors. The main goal of this study is to assess whether, for retrospective
      studies, MRI data may serve as a common basis for encompassing asymmetry in
      diagnosis established according to the WHO or Ste-Anne (SA) classification.
      PATIENTS AND METHODS: This study included 251 adult patients in whom a SA grade A
      or B oligodendroglioma or oligo-astrocytoma was newly diagnosed at our
      institution from 1984 to 2003. Routine histological preparations and post
      contrast preoperative MRI/CT-scan were simultaneously reviewed in order to assess
      the impact on survival of the following features: presence or absence of a
      polymorphous or gemistocytic astrocytic component, of necrosis and of contrast
      enhancement (CH); endothelial hyperplasia (EH) assessed as absent, present minor
      (HE+) or (HE++) when conform to the threshold of HE defined in the SA grading
      system of oligodendrogliomas. The tumors were graded A: no CH and no EH; in B: CH
      and /or HE++, and A/B: EH + but no CE. RESULTS: 70.1% of the tumors were
      classified as "pure" oligodendroglioma, 19.5% as "polymorphous oligo
      astroastrocytoma" and 10.3% as "gemistocytic oligo-astrocytoma". In grade A, or B
      tumors, the presence of a polymorphous or a gemistocytic component had no
      significant influence on survival; however respectively 53% and 65% of these
      tumours versus 32% of "pure" oligodendrogliomas were grade B at the time of
      diagnosis. In either histological subtypes, survival was not significantly
      different when HE was absent or minor (HE+). After regrouping of the histological
      subtypes and of the tumors with HE+ or absent, the series included 153
      oligodendrogliomas grade A and 98 grade B. Survival in patients with grade A
      versus grade B tumors was respectively 142 versus 52 months (p<0.0001). In grade
      B tumors, necrosis had no significant influence on survival. Ring-shaped contrast
      enhancement surrounding large foci of necrosis was observed in only 4 cases. In
      tumors with or without CE, patient survival was respectively 148 versus 40 months
      (p<0.0001). On post contrast MRI done in 235 patients, only 7 tumors (3%) were
      grade A/B (EH++ but no CH). CONCLUSIONS: From these results and our previous
      observation that, according to the SA classification of gliomas, only
      oligodendrogliomas or oligo-astrocytomas may not show CE, we propose that for
      retrospective studies: 1) tumors diagnosed according to the Ste-Anne
      classification as oligodendroglioma or oligo-astrocytoma be regrouped in a unique
      category, 2) independent of their histological type and grade according to the
      WHO, gliomas that do not show CE be regrouped with SA oligodendrogliomas grade A,
      3) concerning gliomas that show CE on MRI: oligodendrogliomas or oligo
      astrocytomas WHO grade II or III, as well as WHO secondary glioblastomas or
      glioblastomas with an oligodendroglial component, be regrouped with SA
      oligodendrogliomas grade B; however tumors that show ring-like CE surrounding
      large foci of necrosis and finger-like "peritumoral" edema should be excluded or
      analysed separately.

PMID- 16292169
TI  - [Spatial delimitation of low grade oligodendrogliomas].
AB  - Image-guided surgery is the central element of therapeutic management of low
      grade gliomas and consequently, a precise preoperative definition of their
      spatial extension is necessary. The question of the present work is: do the
      imaging abnormalities delineate the real spatial development of low grade
      oligodendrogliomas? A review of the literature showed that MRI on T2-weighted and
      FLAIR sequences are used to delineate the spatial developement of these tumours
      and that spectroscopic magnetic resonance imaging is more sensible to appreciate
      it. Moreover, mathematical models and histological studies suggest that MRI does
      not indicate the actual spatial extension of low grade oligodendrogliomas. This
      study focused on histological analysis of biopsy samples performed outside MRI
      imaging abnormalities in patients who harboured a low grade oligodendroglioma. It
      showed that isolated tumour cells were identified beyond imaging abnormalities in
      all of the 17 patients studied. In 15 of those 17 patients, isolated tumour cells
      were identified in the most distant biopsy samples taken outside imaging
      abnormalities. Thus, conventional imaging findings, including MRI on T2-weighted
      and FLAIR sequences, are not able to provide the real spatial development and
      boundaries of low grade oligodendrogliomas.

PMID- 16292170
TI  - [Molecular biology of oligodendroglial tumors].
AB  - Oligodendrogliomas have been the focus of considerable interest over the last
      decade, ever since they were recognized as chemosensitive tumors. However, the
      histological diagnosis remains highly controversial and unsatisfactory.
      Meanwhile, our understanding of glioma oncogenesis improved greatly. Gliomas are
      the consequence of specific genetic or epigenetic alterations - activations of
      oncogenes and inactivation of tumor suppressor genes - resulting in the
      disruption of critical cellular pathways and leading to phenotypic changes. Such
      genetic information complements the existing WHO morphological classification
      and, more importantly, provides additional prognostic markers. Indeed, 1p/19q
      deletion has been correlated with chemosensitivity in oligodendrogliomas, and is
      becoming more and more widely used in clinical practice. There is little doubt
      that emerging techniques, such as CGH-array and gene profiling will be very
      helpful in clinical practice for refining both classification and therapeutic
      indications of oligodendroglial tumors.

PMID- 16292171
TI  - [Gene MGMT and oligodendrogliomas. Fundamental data and short review of the
      literature].
AB  - MGMT (O6 methyl guanine methyl transferase) is a gene involved in DNA repair. Its
      mechanism of action is to remove alkyl groups created by alkylating chemotherapy
      and therefore induces chemoresistances. Recent studies show that this gene
      expression seems to be related to the promoter's methylation, which could predict
      a possible chemosensitivity. The study of MGMT could be of some therapeutic and
      prognostic interest. Few series of oligodendrogliomas have been published and
      their results appear to be controversial. This is probably due to both tumour
      heterogeneity and multiple parameters associated with chemosensitivity. To date,
      it thus appears difficult to choose the adjuvant treatment according to the sole
      status of MGMT.

PMID- 16292172
TI  - [MRI for oligodendrogliomas].
AB  - MRI has dramatically improved the management of cerebral tumors and consequently
      oligodendrogliomas. T1 and T2-weighted images and gadolinium enhancement are very
      useful for tumor detection and characterization. Tumor enhancement is of a great
      prognostic value because it is highly predictive of high-grade oligodendroglioma.
      Three-dimensional MR images provide, with high precision, the anatomical location
      and the relationships with functional structures (motor and language areas). The
      recent technical progress in MRI and the use of diffusion images in the screening
      of tumors lead to a better definition of the lesion. Comparative analysis of MRI
      images is helpful to detect eventual relapse and adverse effects of treatment.

PMID- 16292173
TI  - [Perfusion MR imaging for initial diagnosis and follow-up of brain tumors].
AB  - OBJECT: To discuss the pertinency of perfusion MR imaging for initial diagnosis
      and follow up of brain tumors. METHODOLOGY: Dynamic susceptibility contrast MR
      imaging was applied. Images were thus obtained with intensities proportional to
      the cerebral blood volume (CBV). Relative cerebral blood volume (rCBV) maps were
      then generated by normalizing the signal intensities with respect to measurements
      made in healthy tissue. RESULTS: The method provided interesting data for
      establishing the differential diagnosis between different kinds of lesions, in
      particular between lymphoma and pilocytic astrocytoma, and for grading gliomas.
      DISCUSSION AND CONCLUSION: Limits of the approach are discussed, in particular
      with respect to quantification aspects and interpretation of the results. The
      approach could be particularly useful for grading oligodendrogliomas, for which
      histological diagnosis on biopsy is sometimes difficult.

PMID- 16292174
TI  - [Proton magnetic resonance spectroscopy (1H-MRS) for the diagnosis of brain
      tumors and the evaluation of treatment].
AB  - MR spectroscopy (MRS) is a technique used to study a few metabolites in the brain
      or tumors in situ. This technique can provide information on tumor histological
      type and grade, and is helpful to identify tumor-like lesions, particularly
      abscesses. MRS can be used for treatment monitoring.

PMID- 16292175
TI  - [Metabolic imaging for supratentorial oligodendrogliomas].
AB  - Metabolic imaging with positron emission tomography (PET) provides, in neuro
      oncology, information complementary to that provided by anatomic imaging obtained
      with CT-scanner or MRI. Only a few publications have yet reported its use in
      oligodendroglial tumors. These findings and partial results obtained in ongoing
      work, suggest some preliminary conclusions: 11C-MET (L-methyl-methionine) is a
      more appropriate tracer than 18F-FDG (fluoro-deoxy-glucose), in terms of both
      specificity and sensitivity, for the assessment of patients with this category of
      tumor. PET/MET allows differentiation between grade II and grade III
      oligodendrogliomas; better targeting for stereotactic biopsy; more accurate
      assessment of the post-operative residual tumor; identification of progression
      from low-grade to anaplastic grade during the disease course; differentiation
      between recurrence and a post-radiation processes. PET/MET allows, to some
      extent, prediction of response to radiotherapy; and, probably, to chemotherapy.

PMID- 16292176
TI  - [Functional MR imaging and oligodendrogliomas].
AB  - The localization of functional areas obtained from functional MRI (fMRI) is
      useful for patients suffering from tumors contiguous to eloquent brain areas.
      fRMI is an efficient tool in the strategy of treatment of low grade
      oligodendroglioamas in the rolandic area in intact or slightly impaired patients.
      It can be used preoperatively to assess motor functional areas. Indeed there is a
      good correlation for motor cortex lesions when using comparison between fMRI and
      intraoperative findings. Direct integration of fMRI data into neuronavigation
      enables to better visualize and preserve eloquent brain areas. One must be aware
      of fMRI limits. It is still often used with the control of direct cortical
      stimulations.

PMID- 16292177
TI  - [Results of the Sainte-Anne - Lyons series of 318 oligodendroglioma in adults].
AB  - INTRODUCTION: Incidence of cerebral oligodendrogliomas is increasing because of
      better recognition made possible by improved classifications. We studied a
      homogeneous series using the Sainte-Anne grading scale in order to better
      understanding the history of these tumors with or without treatment and to assess
      prognosis and associated factors. PATIENTS AND METHODS: A retrospective series of
      318 adult patients with oligodendroglioma (OLG) treated at Hopital Sainte-Anne,
      Paris (SA) and Hopital Neurologique, Lyons (L) between 1984 and 2003 was
      analyzed: 182 grade A OLG (SA + L), 136 grade B among which a homogenous series
      of 98 (SA) were included. For grade A: age at diagnosis ranged from 21 to 70
      (mean: 41), sex ratio was 1.28. For grade B: age at diagnosis ranged from 12 to
      75 (mean: 45.5), sex-ratio was 1.58. The main first symptoms were: epilepsy (A:
      91.5%; B: 76%), intracranial hypertension (A: 7.9%; B: 14.6%), neurological
      deficit (A: 5.1%; B: 17.7%). The most frequent locations were: frontal, insular
      and central for both A and B. Mean size was 55 mm for grade A, 62 mm for B.
      Calcifications were found in 20% of A, 48.5% of B. No tumor was enhanced on
      imaging (CT/MRI) in grade A, all but 7 in grade B. All patients underwent surgery
      either for biopsy (A: 47.2%; B: 53%), or removal which was partial (A: 26.4% vs
      B: 19.4%) or extended (A: 36.3% vs B: 37.8%). Fifty-six patients underwent 2
      procedures and 12 three procedures. Radiotherapy was performed in 76.9% of grade
      A, and 91% of B patients, in the immediate postoperative period for 71% A and
      82.7% B. Chemotherapy was delivered for 36% of grade A (in the event of
      transformation to grade B or failure of radiotherapy) and 67.5% of B patients.
      Among grade A tumors, 38% transformed into grade B within a mean delay of 51
      months with a mean follow-up of 78 months. RESULTS: Median survival was 136
      months for grade A and 52 for grade B. Survival at 5, 10 and 15 was 75.5%, 51%
      and 22.4% for grade A vs 45.2%, 31.3% and 0% for grade B respectively. In
      univariate and multivariate analysis, grade A survival was associated with age at
      diagnosis, tumor size, large removal and response to radiotherapy. Grade B
      survival was associated with age at diagnosis, wide removal and sharply defined
      limits of the tumor on imaging. CONCLUSIONS: Analysis of both published data and
      this series underlines many prognostic parameters. It shows that OLG are
      heterogeneous tumors even in each grade (A and B). Treatment should consequently
      progress towards more targeted procedures for patients mainly with postoperative
      radiotherapy and chemotherapy.

PMID- 16292178
TI  - [Adult supratentorial oligodendrogliomas. Surgical treatment: indications and
      techniques].
AB  - Surgical resection is the first step in the treatment of adult supratentorial
      oligodendrogliomas (OLG). However, the role of resection on prognosis, the most
      appropriate time for surgery along the natural history of those tumors, and the
      best operative strategy remain debated. Survival curves after resection vary
      greatly among reported series, in particular as a result of a persisting
      confusion in identification and classification of cerebral OLG. Surgical or
      stereotactic biopsy is the first surgical procedure which enables confirmation of
      the diagnosis suggested on imaging, assessment of extension of tumor cell
      infiltration beyond abnormalities limit described an imaging, and currently
      available molecular biology studies. Biopsies may be the only surgical procedure
      in patients having a deep-seated tumor with minimal mass effect, or prior to a
      surgical resection or a "wait and watch" strategy. Surgical resection is
      indicated for the other patients. However, it has not been demonstrated that time
      for resection has an influence on survival, excepted in patients with rapidly
      growing tumors, with mass effect causing increased intracranial pressure. A wait
      and watch strategy is therefore warranted in patients with a tumor aspect
      suggestive of a grade A OLG; surgical resection may be indicated later. There is
      a current trend for maximal safe resection, preserving functional cerebral areas,
      since truly complete resection of the tumor including infiltration is
      exceptional. However, from the contradictory results reported to date, one cannot
      ascertain whether large or complete resection based on imaging is associated with
      significantly longer survival. Neuronavigation guidance, intraoperative imaging,
      and cortical stimulation techniques are helpful neurosurgical techniques enabling
      maximal safe resection with preservation of functional areas.

PMID- 16292179
TI  - [Usefulness of direct electrical stimulations during surgery for gliomas located
      within eloquent brain regions].
AB  - Glioma surgery in functional areas has undergone a dramatic development these
      last few years, thanks to improvements in both intraoperative functional imaging
      and direct electrical stimulation of cortical areas or association pathways. The
      goal of these techniques to achieve complete as possible surgical removal of
      tumors located in eloquent areas (sensitive, motor and language areas) with
      minimal risk of permanent sequelae. To be reliable, a rigorous methodology is
      required. Current cortical mapping is very easy to achieve, whereas mapping of
      association pathways will require much more experience. In case of tumors located
      in somatosensorial or language areas, the difficulties related to accurate sub
      cortical localization are combined with these of local anesthesia and the best
      task choice to evaluate the integrity of cognitive functions. These functional
      techniques allow total or sub total removal in 52% to 76.2% of patients.
      Transient worsening is observed in 13% to 80% of the patients; the rate of
      permanent sequelae averages 4%.

PMID- 16292180
TI  - [Place of chemotherapy and radiotherapy in the management of oligodendrogliomas].
AB  - Twenty years ago, the discovery of the chemosensitivity of anaplastic
      oligodendrogliomas considerably boosted interest for these tumors. In spite of
      difficulties for histological diagnosis, numerous studies on radiotherapy and
      chemotherapy for oligodendrogliomas appeared these last years. They allowed to
      detail the appropriate role for these therapeutics. For low grade
      oligodendrogliomas, radiotherapy delays the anaplastic transformation, but does
      not modify the overall survival; its indication has to be discussed particularly
      in the absence of clinical symptoms. Chemotherapy seems to be effective for low
      grade oligodendrogliomas as well as anaplastic tumors. However, phase III studies
      are necessary to clarify the contribution of chemotherapy for the treatment of
      low grade oligodendrogliomas, mainly in relation to radiotherapy. In anaplastic
      oligodendrogliomas, in spite of the lack of phase III studies, radiotherapy seems
      to be effective. Chemotherapy is clearly effective, but the most appropriate
      timing (neoadjuvant, adjuvant, at recurrence) is unknown. Results of current
      prospective studies are awaited. Recently, molecular genetic analysis,
      particularly the loss of 1p and 19q chromosomes appears to demonstrate a genetic
      influence on both prognosis and response to treatment.

PMID- 16292181
TI  - [Oligodendrogliomas and radiosurgery].
AB  - Radiosurgery of oligodendrogliomas is not specific. It must be integrated into
      the overall treatment scheme for gliomas which remains to be strictly defined.
      Nevertheless, empirically, and in light of the limited constraints for the
      patient and the encouraging radiological and clinical benefits, radiosurgical
      teams usually propose this technique in the event of recurrence of malignant
      gliomas, as a second line treatment. Exceptionally radiation can be used for some
      small benign gliomas which could not be treated by open surgery and accurately
      defined radiologically. Radiosurgery can achieve local control of the lesion,
      mostly transitionally, with 15 to 18 Gy at the reference isodose. One of the key
      problems is the definition of the glioma boundaries. Despite progress in
      neuroimaging techniques most the limits of malignant forms are still not
      accessible. In routine practice, the nodular area, considered as the most active
      on MRI, i.e. the contrast enhanced area, is accepted as the target. Its widest
      dimension must be about 35-40 mm. Only patients with minimal disability can
      benefit from radiosurgery. Optimization of the target definition (in particular
      the most active zone) and prospective randomized studies should be helpful in
      clarifying indications for this technique.

PMID- 16292182
TI  - [Pediatric supratentorial oligodendrogliomas: Marseilles and Lyons experiences].
AB  - BACKGROUND AND PURPOSE: The goal of this study was to analyze the main aspects of
      oligodendrogliomas observed in children. METHOD: The records of 35 children aged
      15 years or younger (23 from Marseilles and 12 from Lyons) were reviewed.
      Clinical signs and symptoms, imaging findings (CT scan and pre- and post
      operative MRI), extent of surgical resection, histology according to the WHO and
      Ste-Anne grading and survival were analysed. Considering all these factors, a
      statistical analyzis was undertaken in order to identify prognostic factors.
      DISCUSSION AND CONCLUSION: Oligodendrogliomas are rare tumors in children. The
      most important differential diagnosis to discuss is dysembryoplastic
      neuroepithelial tumor. Our study allowed us to distinguish several subgroups of
      patients with a different prognosis: thalamic tumors with a dismal prognosis
      versus hemispheric tumors. A group of cortical tumors we called "DNT-like"
      (hemispheric cortical tumor, isolated epilepsy, without neurological deficit and
      reased ICP, without edema and mass effect on MRI) with an excellent prognosis
      like the group with epilepsy. Histological grading (grade A/grade B and grade
      II/grade III) is also a prognostic factor.

PMID- 16292183
TI  - Cerebral oligodendrogliomas in adults and children. Current data and
      perspectives.
AB  - Cerebral oligodendrogliomas represent more than 30% of glial tumors in adults.
      Mean age at diagnosis is 41 for grade A and 45(1/2) for grade B, epilepsy being
      the main revealing symptom (91.5% of A, 76% of B). Survival at 5, 10 and 15 years
      is respectively 75.5%, 51% and 22.4% for grade A (median: 136 months), and 45.2%,
      31.3% and 0% for grade B (median: 52 months). It is influenced by age at
      diagnosis: median, before 40 years of age, is 12 years for A and 8(1/2) for B;
      between 40 and 60, is 12 years for A and 4(1/2) for B; over 60, is 4 years for A
      and 1(1/2) for B. In children, they represent less than 2.5% of cerebral tumors
      and include 23% grade A and 77% grade B (48.5% WHO grade II and 51.5% WHO grade
      III). Mean age at surgical removal is 9.5 +/- 5 years. One third are hemispheric,
      2/3 are revealed by epilepsy. A complete surgical removal is performed in 60%.
      Mean survival is 13 years (154 +/- 20 months), with a mortality at 5 and 10 years
      of 60% +/- 9%, and a risk of recurrence of 54% +/- 9% at 5 years and 46.5% +/-
      10.5% at 5 years. The main differential diagnosis of grade A oligo is
      dysembryoplastic neuroepithelial tumors (DNT). Inversely, thalamic locations,
      most often grade B, generally present with a motor deficit; complete removal can
      be achieved in only 15%. The only efficient treatment is chemotherapy, requiring
      search for chemosensitivity (1p19q deletion, expression of MGMT gene, analysis by
      MR-spectroscopy and TEP). Logically, surgical debulking should be as wide as
      possible, but with preservation of neurological and cognitive functions with the
      help of modern imaging progresses (fMRI, diffusion and perfusion MRI,
      tractography, PET) and operative techniques (navigation, cortical stimulation,
      and even opertaive MRI). Tumors presenting clinical and radiological progression
      should be removed. Operative mortality varies from 0 to 6%, transient morbidity
      from 20 to 25%, definit morbidity from 5 to 10%. Radiotherapy does not
      significantly modify survival whatever the delivered dose. The important point is
      the patient's radiosensitivity: survival is 148 months for radiosensitive
      patients versus 12 months for non responsive patients. Studies and development of
      pretherapeutic assays of tumoral radiosensitivity will be a fundamental research
      axis (PET, sample studies).

PMID- 16292184
TI  - [Does the new protocol for breast cancer screening modify performance
      indicators?].

PMID- 16292185
TI  - [Asthma control in general practice: a cross-sectional survey of 16,580
      patients].
AB  - INTRODUCTION: Little information is available about asthma control in patients
      followed by general practitioners care in France, although such control is one of
      the essential aims of their treatment. OBJECTIVES: The ER'Asthme survey sought to
      assess asthma control among patients visiting their general practitioner (GP) and
      to determine the factors associated with it. METHODS: This cross-sectional
      included patients with asthma diagnosed at least 12 months earlier, aged more
      than 6 years, and followed by a GP. It collected data on self-assessed health
      status, asthma control (assessed by a 3-level composite score based on the
      Canadian consensus criteria as adapted by ANAES: optimal, acceptable and
      unacceptable), and compliance. RESULTS: The study included 16,580 patients; 85%
      were older than 20 years, and 54% were male. Patients answered the question about
      their asthma control as follows: 53% "excellent" or "fine", 39% "not very good"
      and 8% "poor". GPs, however, assessed asthma control as optimal in 21% of
      patients, acceptable in 7% and unacceptable in 72%. Concordance between these two
      assessments was thus poor: Kappa coefficient 34.5% (95% CI [33.5%; 35.5%]). Only
      59% of patients reported complete compliance with their maintenance treatment.
      Factors associated with optimal control were: use of fixed combination therapy
      (inhaled corticosteroid+long-acting beta-agonist) (OR: 3.7; 95%CI [3.5; 4.2])
      normal BMI (OR: 2.4; 95%CI [2.0; 2.9]), non-smoker status (OR: 2.4; 95%CI [2.1;
      2.8]), age<50 (OR: 2.3; 95%CI [2.1; 2.6]) and good compliance (OR: 1.6; 95%CI
      [1.5; 1.8]). CONCLUSION: Patients with asthma overestimate their asthma control,
      which often remains inadequate. Maintenance treatment with a fixed combination,
      BMI, smoking, age and compliance all influence the level of asthma control.

PMID- 16292186
TI  - [Attitude toward insomnia: survey of 6043 French general practitioners].
AB  - AIM: To describe the attitudes of French general practitioners (GPs) about
      insomnia and its effect on patients' physical health and work. METHOD: A
      questionnaire about patients with insomnia and its diagnosis, treatment, and
      consequences was distributed to a representative sample of 8000 GPs. RESULTS:
      6,043 GPs completed and returned the questionnaires. They estimated the
      prevalence of insomnia in their patients at 18.1%. They identified the principal
      causes of insomnia as anxiety (58.8%) and work issues (54%). Nearly 45% reported
      that they always raise the subject of sleep with their patients. For 62.4% sleep
      problems reflect another disorder rather than being a primary syndrome. Nearly
      two-thirds (60.2%) do not prescribe medication at the first complaint. When
      prescribing hypnotics, 81.3% also recommended sleep hygiene measures. Most
      (68.5%) agreed that insomnia affects concentration, memory, and attention. Almost
      all employed patients with insomnia complained of work-related effects, such as
      loss of productivity and absenteeism. CONCLUSION: Insomnia and its management are
      topics of strong interest for GPs.

PMID- 16292187
TI  - [Sensitization to powdered latex gloves: prevalence in hospital employees].
AB  - INTRODUCTION: The prevalence of latex allergies in industrial countries has
      skyrocketed since the 1980s. Between 2.6 and 22% of hospital workers are
      diagnosed with latex allergy, which has been recognized as an occupational hazard
      in France since 1997. AIM: To assess the prevalence of latex allergy among
      Montpellier University Hospital Center staff. METHODS: From 1999 to 2002, we
      interviewed and conducted skin-prick tests on 537 hospital staff members from
      different departments and with different degrees of exposure to airborne latex
      allergens. RESULTS: Symptoms while using natural-rubber latex gloves (most often
      contact dermatitis) were reported by 88 (16.4%) staff members. Overall work
      related allergic symptoms included rhinitis, reported by 65 (12.1%), contact
      urticaria by 28 (5.2%), and bronchial symptoms by 16 (1.1%). In all,
      sensitization to latex was identified in 7.1% of our staff, and this percentage
      was higher (11.3%) in units where latex gloves were used more often.
      Sensitization was associated with high latex exposure and atopy. CONCLUSION: This
      high rate of latex sensitization and the risk factors are similar to those
      already published. Based on this study, we have eliminated powdered latex gloves,
      as have many other hospitals.

PMID- 16292188
TI  - [Hypoglycemic coma revealing a solitary fibrous tumor of the pleura].
AB  - INTRODUCTION: Solitary fibrous tumor of the pleura (TFSP) is rare. When
      associated with hypoglycemia it is commonly referred to as Doege-Potter syndrome.
      CASE: A 51-year-old man was hospitalized for recurrent near-syncope associated
      with hypoglycemia. Clinical examination and then thoracic imaging clearly showed
      anomalies that corresponded to a mass occupying the entire left hemithorax. After
      resection, histological analysis diagnosed a fibrous tumor of the pleura.
      DISCUSSION: Solitary fibrous tumors of the pleura are observed most often in
      patients aged 50 and 70 years. Hypoglycemia is rare, occurring in approximately
      4% of cases. It is explained by the abnormal secretion of a type-II insulin-like
      growth factor. This tumor is treated by complete surgical excision.

PMID- 16292189
TI  - [Trichomonas tenax in pulmonary and pleural diseases].
AB  - INTRODUCTION: Trichomonas is a protozoan rarely incriminated in pulmonary or
      pleural disorders. CASE: An 84-year-old man, under treatment for chronic lymphoid
      leukemia with hypogammaglobulinemia, was hospitalized for respiratory distress
      and fever due to bilateral pulmonary and pleural disorders. Direct examination of
      the bronchoalveolar lavage fluid revealed a flagella protozoan identified as
      Trichomonas tenax. DISCUSSION: Although Trichomonas is rare in pulmonary
      disorders, when it occurs, T. tenax appears to be the most common species.
      Treatment with metronidazole was effective.

PMID- 16292190
TI  - [Carcinomatous mediastinitis secondary to carcinoma of the bladder].
AB  - INTRODUCTION: This is the first reported case of a histologically-proved
      mediastinal metastatic site of a transitional cell carcinoma of the bladder.
      CASE: A 61-year-old woman who had undergone a total cystectomy 3 years earlier
      for transitional cell carcinoma was hospitalized for dysphagia. Endoscopy showed
      impassable stenosis beginning 25 cm below the dental arch, without any developing
      endoluminal lesion. Histologic analysis of the biopsy samples identified
      transitional cell carcinoma infiltration of the muscularis and deep mucosa of the
      esophagus. DISCUSSION: Three years after a diagnosis of bladder cancer, invasion
      of the paraesophageal lymph nodes was accompanied by infiltration of the
      esophageal muscularis and contiguous mucosa. Esophageal stenoses by carcinomatous
      mediastinitis are rare; when they occur, it is usually secondary to breast
      cancer. They are generally treated endoscopically, which entails a risk of
      perforation.

PMID- 16292191
TI  - [Management of severe acute asthma in adults].
AB  - Any life-threatening episode of asthma requires early pre-hospital specialized
      medical management by emergency medical crews. Gravity depends on both clinical
      criteria and a peak expiratory flow rate (PEFR) more than 30% below either the
      level predicted by the reference graph or the patient's reference value. Initial
      treatment combines continuous nebulizations containing a beta2-agonist and
      ipratropium bromide, with oxygen administration and intravenous corticosteroid
      bolus. Recommended as second-line treatment in the absence of adequate response
      are: intravenous magnesium sulphate and continuous-perfusion beta2-agonists
      (electric syringe), or, in the case of shock, epinephrine. If mechanical
      ventilation is required, its settings should aim for low tidal volumes, low
      frequency, and increased expiratory time.

PMID- 16292192
TI  - [FGF23, a "new" hormone regulating phosphate homeostasis and vitamin D
      metabolism].
AB  - Until recently, the action of two hormones - parathyroid hormone (PTH) and
      calcitriol - on three target tissues - bone, kidney, and gut - has been thought
      to regulate the closely linked homeostasis of calcium and phosphates. In this
      system, an increase in the plasma concentration of one ion often leads to a
      reciprocal change in the concentration of the other and PTH stimulates 1 alpha
      hydroxylase activity and calcitriol synthesis in renal proximal tubular cells. A
      second phosphate regulation system was recently identified. It involves one or
      more phosphaturic hormones, called "phosphatonins", that is, circulating factors
      with potent phosphaturic activity. The key phosphatonin appears to be a
      fibroblast growth factor, known as FGF23. It is now established that FGF23
      regulates not only phosphate homeostasis, but also vitamin D metabolism. In
      contrast to PTH, however, FGF23 inhibits rather than stimulates 1 alpha
      hydroxylase activity and calcitriol synthesis.

PMID- 16292193
TI  - [Iron overload and insulin resistance].
AB  - There is increasing evidence that moderately elevated body iron stores, below
      levels commonly found in genetic hemochromatosis, may be associated with adverse
      health outcomes. Genetic hemochromatosis, characterized by transferrin saturation
      (TS) greater than 45%, is most often linked to homozygosity of the HFE C282Y
      allele. The phenotype is also modulated by mutations of more recently discovered
      genes (including ferroportin, hemojuvelin, hepcidin, and transferrin receptor)
      and environmental factors (including alcohol, viruses, diet, blood loss). Iron
      overload without hemochromatosis is characterized by high levels of serum
      ferritin and normal TS, as seen in dysmetabolic hepatosiderosis. Elevated serum
      ferritin levels predict incident type 2 diabetes in prospective studies and have
      been associated with hypertension, dyslipidemia, glucose tolerance disturbances,
      central adiposity, and metabolic syndrome. High ferritin levels are not
      synonymous with iron overload and may in some cases be a simple marker of insulin
      resistance.

PMID- 16292195
TI  - [Semmelweis, a medical tragedy].

PMID- 16292196
TI  - [Vaccination against infectious threats].

PMID- 16292194
TI  - [Emphysematous pyelonephritis].

PMID- 16292197
TI  - [Results of surgical treatment for renal artery dysplasia].
AB  - PURPOSES: To retrospectively assess functional results of surgical treatment for
      renal artery dysplasia. PATIENTS AND METHOD: From January 1992 to December 2001,
      11 symptomatic patients including 9 women (mean age 47 years, range 23-67),
      underwent surgery for renal artery dysplasia. Three patients presented with
      normalized hypertension, three others presented with isolated systolic
      hypertension, and the five remaining presented with grade II or III hypertension.
      Angiograms showed evidence of dysplasia of 16 renal arteries. Six arteries showed
      stenosis (37.5%), four aneurysms (25%), four both (25%), and two arteries showed
      wall irregularities (12.5%). Endovascular revascularizations were performed in
      five patients (45%) during the treatment of six renal arteries (37.5%). All
      endovascular procedures were angioplasties without any stent placement. Six
      patients (55%) underwent conventional procedures (in situ or ex-situ surgery) for
      the treatment of seven renal arteries (44%). RESULTS: In the short term, the
      treatment had a significant decrease on the systolic arterial pressure (p=0.019)
      and in the number of drugs used (p=0.009), but was not significant in the
      diastolic arterial pressure (p=0.084). The benefits persisted after two years of
      follow-up (PAS, p=0.023, PAD, p=0.047, drugs p=0.03). Benefits persisted in all
      of the six patients who had had hypertension for less than five years. There was
      60% functional failure in the treatment of the five patients with a more than
      five years history of hypertension. CONCLUSION: This study confirms the short and
      long term's beneficial results of the surgical treatment of symptomatic renal
      artery dysplasia. Rapid care of those patients should optimize the functional
      results.

PMID- 16292198
TI  - [Critical chronic ischemia of the limbs: organization of the management of a
      malignant disease].
AB  - Chronic critical ischemia of the limbs (CCIL) typically raises the problem of
      early diagnosis and specialized treatment. The challenge is considerable since
      the incidence of CCIL is in the range of 500 to 1,000 patients/million
      inhabitants/year, with an incidence of major amputations from 100 to 300/million
      inhabitants/year. Mortality of these patients reaches 20% at 6 months and more
      than 80% at 10 years, which places the CCIL in the group of highly malignant
      oncological diseases. Despite therapeutic advances, the rate of amputations
      continues to progress especially in diabetics whose life expectancy is increasing
      due the excellent contribution of coronaropathy. Prequisites are summarized in
      the TASC consensus and in the discussions conducted during the creation of
      vascular centres: multidisciplinary teams, arteriopathy register (including CCIL
      and center audits), development of protocols (evaluation cost - efficiency of
      revascularization and medical treatments, evaluation of angiogenesis projects),
      collaboration between vascular centers and networks. CCIL is a malignant disease
      with an increasing incidence implying early and specialized care; means exist but
      efforts have to be made regarding their evaluation and coordination.

PMID- 16292200
TI  - [Celiac disease, cerebral venous thrombosis and protein S deficiency, a
      fortuitous association?].
AB  - INTRODUCTION: Celiac disease is a pathology which is rarely associated with
      thrombosis complications. Cerebral vascular thrombosis has never been described
      in patients with a celiac disease. OBSERVATION: We report an observation of a 21
      year-old girl with a history of celiac disease who was hospitalized in the
      intensive care unit for convulsive status epilepticus secondary to a cerebral
      venous thrombosis. The etiologic investigation of this thrombo-embolic
      complication revealed protein S deficit. Our patient improved under symptomatic
      treatment. COMMENT: This original observation confirms that celiac disease can be
      associated with cerebral venous thrombosis.

PMID- 16292199
TI  - [Optimizing history taking for evaluating the risk of venous thromboembolism: the
      OPTIMEV study].
AB  - Venous thromboembolism (VTE) is a frequent disease and remains a major cause of
      mortality and morbidity among our patients. During the 20 past years, clinical
      description, diagnostic tools, and treatment have changed dramatically. Most
      published data describing risk factors for VTE no longer apply to the patients
      seen in daily practice. We present here the rationale, aims, and methodology of
      the OPTIMEV Study (OPTimisation de l'Interrogatoire pour la Maladie
      thromboEmbolique Veineuse). RATIONALE: Risk factors for VTE are numerous, complex
      and interactions between them and their clinical importance is difficult to
      measure (table I). For example, odds ratios for VTE recurrence vary greatly
      across longitudinal studies. We searched the National Library of Medecine
      (PubMed) and the Amedeo website using the following keywords: "venous
      thromboembolism", "pulmonary embolism", "deep vein thrombosis", "risk factors".
      We selected 84 relevant articles published between 1972 and 2005. Based on this
      literature analysis, we identified the following major risk factors: VTE
      recurrence, surgery, cancer, immobilization, age, biological factors. For these
      factors, data are lacking and some questions are proposed. OBJECTIVES: The broad
      objective of the study is to better evaluate clinical risk factors that fit
      today's practice against VTE. Specific aims are: 1) to determine whether risk
      factors are different between proximal and distal deep vein thrombosis (DVT); 2)
      to develop and prospectively validate a new prediction rule for outpatients. The
      primary hypothesis is that careful assessment of VTE recurrence, adequate
      surgical thromboprophylaxis, cancer staging, and varicose vein stratification
      according to the CEAP classification, is mandatory for accurate evaluation of
      thromboembolic disease risk. METHODS: We conducted a multicenter, prospective,
      cohort study of 10000 patients. Enrollees are inpatients and outpatients
      presenting with a clinical suspicion of VTE in Emergency Departments and
      outpatient clinics in France. 4173 patients have been enrolled at this time
      (Figure 2). All eligible patients are enrolled during a selected period of time
      through different seasons. Data are collected by physicians in charge of the
      patients using an electronic case recording form. Collected data include baseline
      characteristics, risk factors, results of diagnostic investigations. Outcome
      measures obtained through telephone interview at 3 and 12 months include cancer
      diagnosis, VTE recurrence, haemorrhagic events, treatments, death. Univariate and
      multivariate analysis will be performed using multilevel logistic regression. The
      study organization is performed by the Centre d'Investigation Clinique de
      Grenoble and is sponsored by the French Society of Vascular Medicine. First
      results, to be published in 2006, will allow development of new prediction rules
      for VTE diagnosis.

PMID- 16292201
TI  - [Jugular thrombosis with fever: what about Lemierre syndrome?].

PMID- 16292202
TI  - [On intermittent arterial claudication].

PMID- 16292203
TI  - [Glomic tumor of the finger].

PMID- 16292204
TI  - [You said Critical Reading of Articles?].

PMID- 16292205
TI  - [Laparoscopic fundoplication: current data].
AB  - Laparoscopic fundoplication is as effective as its open counterpart, allowing
      reduced morbidity, shorter hospital stay and recovery, lower consumption of
      analgesics, and very low mortality, with no significant differences in early
      functional outcome. Rate of early recurrence is similar after partial and total
      fundoplication, but but the partial approach has a significantly reduced rate of
      reoperation for failure, mainly due to postoperative dysphagia. Long-term follow
      up is required to evaluate dysphagia and quality-of-life.

PMID- 16292206
TI  - [Rationale for oncological surgery in multimodal cancer treatments].
AB  - The permanent dissemination of circulating cancer cells from infiltrative cancers
      renders the notion of localized cancer obsolete. This raises the question of the
      role of treatments such as surgery which are localized in time and space.
      Moreover, it is now proven that surgery increases the number of circulating
      cancers cells and produces transient immunodepression which promotes cancer cell
      implantation. In addition, the healing process stimulates growth factors, which
      also act on tumor growth. In spite of these deleterious effects, oncological
      surgery remains an important tool in the anti-cancer armamentarium. Optimal
      cytoreductive surgery facilitates the effect of adjuvant treatments by
      eliminating the vascular sanctuaries present in the center of any large tumor and
      by its effect as a striking-force very localized in time and space. Oncological
      surgery must evolve as an integrative part of our improving understanding of
      tumor biology, taking into account recent developments in functional imaging,
      genomics and proteomics. Modalities and timing must be reconsidered for
      oncological surgery to play its proper role as one of the many components
      contributing to multimodal cancer treatments. New modalities will undoubtedly be
      necessary with the development of future technologies.

PMID- 16292208
TI  - [Left hepatectomy].

PMID- 16292207
TI  - [Biotherapy in colorectal cancer].
AB  - Strategies for the treatment of metastatic colorectal cancer must take into
      account the contribution of monoclonal antibodies. A group of new efficient tools
      in oncology, these drugs target tumor antigens. Bevacizumab recognizes VEGF.
      Vascular endothelial growth factor (VEGF) is a key mediator in angiogenesis. This
      antibody combined with chemotherapy increases the survival of patients treated
      for metastatic colorectal cancer. Median survival of patients treated with
      antibodies and chemotherapy is 20 months, compared with only 15 months for
      patients treated with chemotherapy alone. Cetuximab is a monoclonal antibody that
      binds competitively and with high affinity to the EGF receptor. Cetuximab is
      currently approved for use in patients with pretreated colorectal cancer. EGF is
      a major cell growth factor. The side effects of these new biotherapies are
      different from chemotherapy: bevacizumab affects vascular elements and the most
      common side effect of anti-EGFR treatment is acneiform skin rash.

PMID- 16292210
TI  - [Greater saphenous stripping].

PMID- 16292209
TI  - [Milligan and Morgan hemorrhoidectomy].

PMID- 16292211
TI  - [Adrenal metastasis from a hepatocellular carcinoma with thrombosis of the
      inferior vena cava].

PMID- 16292212
TI  - [Cancer of the rectum with unresectable metastases].

PMID- 16292213
TI  - [Specific forms of cholecystitis: contribution of radiology. 1. Emphysematous
      cholecystitis].

PMID- 16292214
TI  - [Specific forms of cholecystitis: contribution of radiology. 2.
      Xanthogranulomatous cholecystitis].

PMID- 16292215
TI  - [Hydatid cyst of the pancreas].

PMID- 16292216
TI  - [At the crossroads].

PMID- 16292217
TI  - [Entity, identity, speciality].

PMID- 16292218
TI  - [Biphosphonates and maxillo-mandibular osteonecrosis: a ticking bomb].

PMID- 16292219
TI  - [Normal mouth opening in the adult French population].
AB  - INTRODUCTION: Limitation of mouth opening is a frequent symptom in the
      pathologies of the temporomandibular joint. The aim of this study is to establish
      normative basis for this criterion in the French population. MATERIALS AND
      METHODS: Maximal mouth opening was measured by an electronic goniometric device.
      Measurements were taken in 228 people (110 men and 126 women) aged between 18 to
      84 years, representative of the French population. RESULTS: The average mouth
      opening is 50.7 7 mm, but it was greater in the male population. It was also
      greater in tall patients and in younger patients (under 50 years). DISCUSSION:
      Our study is original because it is based on normal subjects and because our
      population sample age is the same as that of the French population. Men have a
      greater mouth opening than women, but this can be due to the fact that they are
      taller. Mouth opening is wider in young subjects, under 50, because they are
      younger and because they are taller. Mouth opening is wider in tall patients,
      whatever their sex or their age.

PMID- 16292220
TI  - [Orbito-temporal plexiform neurofibroma: 6 cases].
AB  - INTRODUCTION: Orbito-temporal plexiform neurofibroma is characteristic of Von
      Recklinghausen neurofibromatosis. We report 6 cases of orbito-temporal plexiform
      neurofibromas and review different aspects of diagnosis, course and treatment.
      PATIENTS AND METHODS: Six patients, 4 males and 2 females, with orbito-temporal
      plexiform neurofibromas were treated between 1986 and 2003. Patient age varied
      between 10 and 29 years (age average=19). Computed tomography and magnetic
      resonance imaging were performed in all 6 patients. Surgical resection of the
      neurofibroma was performed in all patients. RESULTS: The tumor was located on the
      left in 5 cases and on the right in one. Spheno-orbital dysplasia was found in
      all patients and was associated with fronto-temporal meningoencephalocele and
      pulsate exophthalmia. Surgical resection enabled reduction of the neurofibroma.
      Exenteration was performed in all patients because of a nonfunctional eye. Two
      patients underwent cure of fronto-temporal meningoencephalocelus with
      reconstruction of the large wing of the sphenoid using an iliac bone graft and a
      titanium plate. DISCUSSION: Surgery is essential for orbito-temporal plexiform
      neurofibroma but is usually difficult, particularly when the tumor has developed
      increasing the risk of hemorrhage. Bony reconstruction is difficult considering
      the risk of progressive osseous dysplasia. The cosmetic results achieved in this
      patient were considered good.

PMID- 16292221
TI  - [Dental avulsions and blood coagulation disorders].
AB  - INTRODUCTION: We performed a retrospective study of tooth removal for patients
      with coagulation disorders. MATERIAL AND METHOD: The study included 67 patients
      divided into 3 groups according to their coagulation disorder. The first group
      included 31 patients with a congenital disorder, the second 19 patients receiving
      anticoagulant therapy, and the third 16 patients with an acquired disorder. The
      same surgical procedure was used for all patients: alveoli regulation, socket
      preparation with resorbable oxycellulose dressing, and sutures with separate
      stitches. Biological glue and celluloid splints were not used. Depending on the
      severity of the coagulation disorder, factor VIII or concentrated von Willebrand
      factor or Desmopressine was administered for patients in the first group. If
      possible, low-molecular-weight heparin replaced oral anticoagulation for patients
      in the second group. Platelet concentrates were administered for 2 of the
      patients in the third group. RESULTS: Postoperative bleeding was noted in 4
      patients in the first group, 2 in the second and 2 in the third. DISCUSSION: We
      have abandoned the use of biological glue and celluloid splints. The rate of
      bleeding in the first and second group was similar to that reported in the
      literature. We were unable to find any comparable report for the third group.

PMID- 16292222
TI  - [Detection of the sentinal node in squamous-cell carcinoma of the oral cavity and
      oropharynx. Preliminary study].
AB  - INTRODUCTION: The sentinel lymph node is defined as the first relay of the
      lymphatic drainage of the tumor. Isotopic detection of the sentinel lymph node
      and absence of its metastatic invasion should theoretically be predictive of
      total drainage of the tumor. The goal of this study was to evaluate sentinel
      lymph node detectability by lymphoscintigraphy in N0 and/or N1 squamous-cell
      carcinoma of oral cavity and oropharynx and to determine its negative predictive
      value. MATERIAL AND METHOD: Lymphoscintigraphy was used for sentinel lymph node
      detection. The procedure required peritumoral injection of technicium-labeled
      colloids to enable anatomical and cutaneous location of the sentinel lymph node.
      A one-way Tyco-Mallinckrodt probe was used for intraoperative detection of the
      sentinel lymph node. This prospective study included 21 patients with N0 or N1
      squamous-cell carcinoma of the oral cavity and the oropharynx. The surgical
      attitude based on T and N was not modified in this prospective study without
      direct individual benefit for the patient. Neck dissection was achieved without
      difficulty. RESULTS: The sentinel lymph node was identified in 20 out of 21
      subjects. The sentinel lymph node was not identified in one patient with
      recurrence T2N0M0 squamous-cell carcinoma of the oropharynx radiated 3 years
      earlier. The percentage of false-negatives was 12.5% (1 false-negative out of 8
      positive patients), giving a sensibility of the detection method of 87.5% (IC
      (95%)=[47.35-99.68]). This false-negative patient had a T3N0M0 squamous-cell
      carcinoma of the oropharynx with a sentinel lymph node removed in territory III.
      Neck dissection revealed 1 N + R- in the sub-mandibular territory associated with
      27 N-R-. The probability of not finding a metastatic node at neck dissection when
      the sentinel lymph node is not metastatic (negative predictive value) was 92.3%
      (12/13) (IC (95)=[63.97-99.81]). The specificity of the method was 100%, as was
      the positive predictive value, because no sentinel node was diagnosed positive
      wrongly on frozen sections among patients without true histological node
      metastasis. DISCUSSION: For routine care of patients with squamous-cell carcinoma
      of the oral cavity and the oropharynx detection of the sentinel lymph node is
      proposed primarily for patients with T1T2N0 staging. Larger tumors can modify the
      architecture and flow within the lymphatic ducts, and consequently even the
      concept of a sentinel lymph node. Systematic neck dissection is required or T3T4,
      even when N0. Our series of T1T2N0 tumors is too small to enable statistically
      significant conclusions. A low level of false-negative in a larger series would
      be necessary to propose this technique instead of convention neck dissection for
      T1T2 tumors of the oral cavity and oropharynx.

PMID- 16292223
TI  - [Acquired bullous diseases of the oral mucosa].
AB  - Bullous diseases of the oral cavity cause painful erosion. They must be
      distinguished from aphthae and vesicles which may have a similar presentation.
      Acute, chronic and congenital conditions are recognized. Acute lesions may
      involve a polymorphous oral erhythema which has an polymorphous erythematous
      presentation or toxidermia (Stevens-Johnson syndrome, Lyell syndrome, fixed
      pigmented erythema). Examination of the skin and history taking are the keys to
      diagnosis. Patients with chronic bullous diseases may have a congenital condition
      (bullous epidermolysis or lymphangioma) suggested by the age at onset and the
      clinical presentation. Acquired chronic bullous diseases include lichen planus
      and autoimmune bullous diseases. Careful examination is essential to identify
      mucosal or cutaneous involvement and to obtain a biopsy for histological
      examination. Search for antibodies deposited in the perilesional mucosa is
      necessary. Chronic erosive gingivitis is a frequent presentation. Most of the
      patients have cicatricial pemphigoid, lichen planus, and more rarely pemphigus.
      The pinch sign is highly discriminative to differentiate the cause of this
      syndrome. Symptomatic treatment of bullous lesions of the oral cavity include
      adapted diet and correct and early use of antalgesics.

PMID- 16292224
TI  - [Reconstruction of complex tissue loss of the medial canthus].
AB  - The medial canthus is an anatomic and surgical entity. Reconstruction after
      cancerological resection is complex. The purpose of this article is to report a
      reconstruction technique for massive loss of tissue of the medial canthus which
      was applied in 2 patients with 2 years follow-up. Anatomic reconstruction was
      achieved. Each element of the canthus was restored: skin using Mustarde
      temporojugal and frontal flaps, conjunctive using a palatine mucosal graft,
      lacrimal canal using conjuctivo-rhinostomy, the medial canthal ligament using a
      fascia lata graft and transnasal canthopexia. Both patients developed an
      ectropion which required revision surgery. At 2 years, the functional outcome is
      good. Reconstruction allowed adapted social life and the cancer was controlled
      successfully.

PMID- 16292225
TI  - [Kikuchi-Fujimoto disease mimicking thyroid metastasis].
AB  - INTRODUCTION: Kikuchi-Fujimoto lymphadenopathy is a subacute necrotizing
      lymphadenopathy of unknown origin. It usually affects cervical lymph nodes. Lymph
      node biopsy is needed for establishing the diagnosis. This disease must be
      considered as a possible cause of lymphadenopathy of unknown origin, certainly if
      classical clinical features lead to diagnostic confusion. OBSERVATION: A 41-year
      old female presented a thyroid cancer treated by thyroidectomy associated with
      administration of I131. She also presented a right cervical metastasis treated by
      surgery. She had a cervical right cervical lymphadenopathy, hypermetabolic on the
      FDG scan, treated by a modified neck dissection. Microscopy of the surgical
      specimen showed necroziting lymphadenitis. DISCUSSION: Kikuchi-Fujimoto
      lymphadenopathy is a subacute necroziting lymphadenopathy of unknown origin,
      involved more commonly cervical lymph nodes unilaterally. It is more common in
      Asia, predominantly in young women. This lesion has been reported in patients of
      virtually any age or gender. No specific biological findings have been described.
      Lymph node biopsy is needed for establishing the diagnosis. The spontaneous
      course is usually favorable but one fatal case has been reported.

PMID- 16292226
TI  - [Inflammatory myofibroblastic pseudotumor of the tongue].
AB  - INTRODUCTION: Inflammatory myofibroblastic tumor (IMT) is a new entity recently
      described, first in the lung. IMT are found throughout the body. CASE: We report
      a very rare tongue localization in a 22-year-old white woman. After a first
      diagnosis of fibrosarcoma, a new examination of the slide and immunohistochemical
      examination led to the definitive diagnosis of inflammatory myofibroblastic tumor
      of the tongue and not fibrosarcoma. DISCUSSION: IMT are rarely encountered in the
      head and neck region. Only 2 cases of IMT of the tongue have been reported in the
      world literature. Diagnosis of IMT is immunohistochemical. Spindle cells were
      reacted for smooth-muscle actin and vimentin. Treatment is surgical. The
      contribution of radiotherapy is not clear because of the small population of
      patients studied.

PMID- 16292227
TI  - [Ankylosis of the temporomandibular joint: a rare manifestation of ankylosing
      spondylitis].
AB  - INTRODUCTION: The ankylosing spondylitis is a chronic inflammatory rheumatoid
      disease with predilection in the axial structures. The temporomandibular joint
      (TMJ) is involved in 10 to 24% of cases. Ankylosis of the TMJ is exceptional,
      only 11 cases being reported to date. OBSERVATION: A 48-year-old patient had been
      followed since 1987 for severe ankylosing spondylitis. The patient, known to be
      positive for tissue antigen HLA B27, was admitted for limitation of mouth
      opening. At physical examination, mouth opening was reduced to 1cm with no
      mandibular movements and a stiffness of the cervical spine in flexion. Computed
      tomography of the TMJs highlighted a bilateral lesion with ankylosis of the left
      joint and of C1-C2. Surgical treatment consisted in block resection of the two
      TMJs using a cartilaginous rib. With a follow up of 9 months, results have been
      satisfactory. DISCUSSION: Complementary explorations should be undertaken in
      ankylosing spondylitis patients with clinical symptoms suggestive of TMJ lesions
      in order to establish the diagnosis and initiate treatment and avoid the
      development of ankylosic forms.

PMID- 16292228
TI  - [Fibrous dysplasia].

PMID- 16292229
TI  - [Conscious sedation by inhalation].

PMID- 16292230
TI  - [Evaluation of tissue response to resorbable osteosynthesis materials in
      maxillofacial surgery. Prospective randomized clinical trial of therapeutic
      strategy].

PMID- 16292231
TI  - [New aspects of diabetes].
AB  - Type II diabetes is a serious, insidious disease which is growing at an
      impressive rate, with 200 million diabetics worldwide and as many who ignore
      their state. Having been seriously studied over more than a century and a half,
      an enormous quantity of knowledge regarding this disease has been accumulated.
      The research we are conducting has allowed us to identify the most important
      actors responsible for diabetes. These are glucose which leads to glyoxal and to
      methylglyoxal which in turn reacts with innumerable targets in the organism
      (including insulin) unless prevented from doing so by detoxifying mechanisms
      (e.g., glyoxalases). The role of microorganisms in the occurrence and development
      of diabetes has also to be seriously examined.

PMID- 16292232
TI  - [Melatoninergic receptor agonists and antagonists: pharmacological aspects and
      therapeutic perspective].
AB  - Melatonin, or N-acetyl 5-methoxytryptamine, a neurohormone produced in the pineal
      gland during periods of darkness, plays a key role in the regulation of circadian
      and seasonal biological rhythms. In mammals, specific MT1 and MT2 receptors are
      located in the central nervous system, mainly in suprachiasmatic nuclei, and also
      in a number of peripheral sites. Besides its chronobiotic action on light
      dependant functions, such as sleep/waking alternance or seasonal depression,
      melatonin exerts modulatory effects on immune, endocrine and metabolic functions.
      However, its short half-life and extensive metabolism lead to a poor
      bioavailability. This prompted to search for metabolically stable analogs
      displaying new and innovative properties. The S 20098 compound, a melatoninergic
      agonist, has proven potent antidepressive and anxiolytic actions. The S 20928
      compound, a melatonin antagonist, was shown to enhance basal metabolism and
      reduce weight gain. Thus, both of these melatonin derivatives open perspectives
      for the development of innovative therapeutic agents in the fields of depression
      and obesity.

PMID- 16292233
TI  - [Placebo and placebo effect].
AB  - The word placebo appeared for the first time in an English medical dictionary in
      1785. In French, it appeared much latter in 1958. This word defines an
      experimental tool used for rigourous evaluation of a specific effect of
      pharmacological treatment and the non specific effect of any therapy. The placebo
      effect is the strictly psychological or psychophysiological effect of a placebo.
      The two principal components of placebo effect as a pain killer, which has been
      extensively studied in this field, are positive expectancies of both the patient
      and the physician. Although the mechanisms of action of placebo effect are not
      well understood, results of several recent works are particularly interesting.

PMID- 16292234
TI  - [Bach flower remedies: a critic of the pseudoscientific, pseudomedicinal concepts
      and philosophical postures inducted by Dr Bach theory].
AB  - Bach Flower Remedies (EFB) are the implements of a so-called alternative pseudo
      therapy, which is increasingly widespread in France. In view of the social impact
      of those alleged complementary health approaches and blurred lines between
      parapharmaceutical trends and those that promote well-being, critical
      investigation seems to be required to promote a piece of objective information on
      this subject. The zetetic methodology appears to be the most effective for
      dealing with the question, we therefore applied a critical study to both EFB and
      alternative therapy of Dr Bach. We show that EFB effectiveness is not formally
      established, that the basic principles of Bach's theory are settled on
      ungrounded, deeply intuitive hypotheses, belong to magical thinking, and do
      promote philosophical approaches that weaken patients-consumers, particularly
      with regard to sectarian trends. We insist on the need for training in effective
      tools for criticism.

PMID- 16292235
TI  - [Elaboration of an interactive educational CD-R on good laboratory practices for
      manufacturing and quality control].
AB  - cGMPs require that QA systems rely upon qualified personnel in charge of
      pharmaceutical operations. In order to achieve this legal requirement, the
      manufacturer must provide initial training and regular re-training along with
      periodical evaluations of their practical efficiency. This cGMP-learning
      multimedia CD-R is an interactive and individual training tool, designed for QC
      laboratory personnel. It contains a final questionnaire allowing an assessment of
      the course efficiency. Building up a ten-module teaching program entitled "Le
      medicament en toute confiance", the development of this CD-R was supervised by an
      European team of experienced industrial pharmacists.

PMID- 16292236
TI  - RSNA Editorial Fellowship: an exciting experience.

PMID- 16292237
TI  - Pulmonary nodule.
AB  - A pulmonary nodule is a frequent and often incidental finding, and still
      represents a diagnostic challenge for radiologists. Although most solitary
      nodules are related to benign disease, some represent stage I lung cancers. and
      need to be distinguished from benign nodules in a cost-effective manner. The aim
      of diagnostic assessment should be to allow early treatment of small malignant
      nodules but avoid unnecessary biopsy or surgery, with their attendant risks, in
      patients with benign disease. The advent of Multislice Computed Tomography (MSCT)
      technology has sparked new interest in the non-invasive assessment of pulmonary
      nodules. Thanks to its ability to scan the whole thoracic volume with thinner
      collimations, this technology allows a more accurate identification and
      characterisation of pulmonary nodules, as well as the determination of perfusion
      patterns and growth rates. In this paper we present an algorithm for the
      diagnostic workup of incidentally detected small pulmonary nodules in subjects
      without known malignancy.

PMID- 16292238
TI  - Low-dose helical chest CT in asbestos-exposed workers in the Veneto Region:
      preliminary results.
AB  - PURPOSE: To evaluate the preliminary results of low-dose helical chest CT in a
      group of individuals with an occupational exposure to asbestos. MATERIALS AND
      METHODS: Between October 2000 and May 2004, 1,512 asymptomatic subjects, selected
      by Occupational Health physicians of the Veneto Region among those with a
      significant exposure to asbestos, underwent low-dose helical chest CT without
      contrast media administration. According to their features, all pulmonary nodules
      identified underwent pathology, further CT evaluation or follow-up with low-dose
      CT. RESULTS: Apart from benign pleural findings (in 40% of subjects), 590
      pulmonary nodules were identified. Eleven nodules underwent pathologic
      examination, which detected 5 malignant lesions, and 51 were evaluated with other
      CT techniques, in all cases demonstrating benign features. In follow-up low-dose
      CT scans, performed in the remaining 528 nodules, a minimal increase in size
      occurred in 4 cases only. CONCLUSIONS: Screening for clinically relevant
      pulmonary lesions in asymptomatic people with occupational exposure to asbestos
      may be useful if rigorous enrollment criteria are adopted. The management of
      abnormal findings is cost-effective if it is based on the morphological features
      of each finding.

PMID- 16292239
TI  - Correlation between HRCT and pulmonary functional tests in cystic fibrosis.
AB  - PURPOSE: To compare the HRCT score by Oikonomou and air trapping in expiratory
      scans with pulmonary functional tests and evaluate which radiological criteria
      are more useful to predict clinical impairment. MATERIALS AND METHODS: From
      January to September 2003, pulmonary HRCT study was performed in 37 patients (23
      males), aged between 7 and 41 years, with cystic fibrosis. In the same day of CT
      examination they also received a complete functional evaluation. HRCT studies
      were evaluated by three radiologists blinded to the clinical data and were
      correlated with the lung function tests. RESULTS: We obtained a high correlation
      (p=0.01) for two of the HRCT signs: extent of mucus plugging and mosaic perfusion
      pattern and all function tests. DISCUSSION: Previous studies have demonstrated
      good correlation between lung function tests, in particular with FEV1,and HRCT
      signs. Our study differed from previous ones in that we analysed the correlation
      between lung function tests and with both single and combined CT criteria.
      CONCLUSIONS: Our results suggest that a simplified HRCT score could be useful to
      evaluate patients with cystic fibrosis.

PMID- 16292240
TI  - Diagnostic accuracy of commercial system for computer-assisted detection (CADx)
      as an adjunct to interpretation of mammograms.
AB  - PURPOSE: To evaluate the diagnostic accuracy of the commercial computer-aided
      detection CADx system for the reading of mammograms. MATERIALS AND METHODS: The
      study assessed the Second Look system developed and marketed by CADx Medical
      Systems, Montreal, Canada. The diagnostic sensitivity was evaluated by means of a
      retrospective study on 98 consecutive cancers detected at screening by double
      independent reading. The specificity and the positive predictive value (PPV) for
      cancer of the CADx system were prospectively evaluated on a second group of 560
      consecutive mammograms of asymptomatic women not included in screening program.
      The radiologist who was present during the test assessed the abnormal
      mammographic findings by one or more of the following diagnostic procedures:
      physical examination, additional mammographic detail views with or without
      magnification, ultrasonography, ultrasound- or mammography-guided fine needle
      aspiration cytology, and core-biopsy. The exams first underwent conventional
      reading and then a second reading carried out with the aid of the CADx system.
      RESULTS: The overall diagnostic sensitivity of the CADx system on the 98
      screening cancers was 81.6%; in particular it was 89.3% for calcifications, 83.9%
      for masses and only 37.5% for architectural distortion. The CADx markings for
      each mammography were 4.7 on average. Identification of invasive carcinoma was
      independent from tumour size. In the second group of 560 mammograms, the CADx
      system marked all cases identified as positive by conventional reading and
      confirmed by biopsy (7/7), but did not permit the detection of any additional
      cancer. The CADx markings per exam were 4.2 on average, the specificity was 13.7%
      and the PPV was 0.55% versus 13.7% recall rate of conventional reading. CADx
      reading led to a 1.96% (11/560) increase of the women necessitating further
      diagnostic investigation. CONCLUSIONS: The results of our study show that the
      diagnostic sensitivity of the CADx system is lower than that obtained by double
      independent reading at screening. Used in association with conventional reading
      of mammograms of asymptomatic women the CADx system did not increase diagnostic
      sensitivity.

PMID- 16292241
TI  - Accuracy of ultrasound in the detection of liver fibrosis in chronic viral
      hepatitis.
AB  - PURPOSE: To assess the accuracy of ultrasonography (US) in the identification and
      grading of hepatic fibrosis in patients afflicted with chronic viral liver
      disease, compared to histological examination as a gold standard. MATERIALS AND
      METHODS: We prospectively studied 105 patients (32 F, 73 M) affected by chronic
      viral liver disease in 36 months. Patients were studied with B-mode US and then
      underwent US-guided liver biopsy. All the patients were studied with conventional
      US with a Sequoia 512, 6.0 (Acuson, Mountain View CA, USA). We evaluated the
      following US parameters: liver margins, parenchymal echotexture, portal vein
      caliber and spleen diameter. The four B-mode US parameters were used for the US
      grading (from 0 to 4). Scheuer's grading (from 0 to 4) was used for the
      histological score. Grades 3 and 4 were considered as positive for fibrosis.
      Sensitivity, specificity, positive and negative predictive values and accuracy
      were calculated in the case of absence, positivity of one or all the US
      parameters. The correlation between US and histological scores was evaluated with
      Spearman's test. RESULTS: At histology seventy-seven patients (73%) had absent
      grade 0 (1 patient; 1%), low-moderate grade 1 (35 patients; 33%) or grade 2 (41
      patients; 39%) liver fibrosis. Twenty-eight patients (27%) had severe grade 3 (16
      patients; 15%) or grade 4 (12 patients; 11%) fibrosis. In the case of absence of
      US parameters sensitivity was 32%, specificity 32%, positive predictive value
      15%, negative predictive value 57% and accuracy 32%. In the case of positivity of
      at least one of the US parameters the values were 68%, 68%, 43%, 84% and 69%. In
      the case of presence of all the US signs the results were 25%, 100%, 100%, 79%
      and 80%. None of the 77 patients with a healthy liver or with low-grade fibrosis
      was positive for all the US parameters. All the patients positive for all of the
      ultrasonographic parameters had high-grade fibrosis or cirrhosis at liver biopsy.
      Correlation between B-mode and histological scores was not statistically
      significant (Rs=0.45; p=0.0001). CONCLUSIONS: US identification of liver fibrosis
      in chronic liver disease is possible with 25% sensitivity, 100% specificity, 100%
      positive predictive value and 79% negative predictive value, with an 80%
      diagnostic accuracy.

PMID- 16292242
TI  - Radiographic and MRI findings in ochronosis.
AB  - PURPOSE: Ochronotic arthropathy is the articular manifestation of alkaptonuria, a
      rare hereditary metabolic disease that leads to the deposition of homogentisic
      acid particularly in the joints where it causes articular degeneration and
      inflammation. We studied the radiological patterns of the disorder using both
      traditional X-rays both MRI and comparing the results obtained with the two
      techniques. MATERIALS AND METHODS: The study included five patients (4 males, 1
      female, mean age 51 years); we studied the most frequently affected sites, the
      knee, the shoulder and the spine. As regards the conventional study we used a
      radiographic score which considered the state of the articular space and the
      presence of calcifications. MRI of the peripheral joints was performed on the
      most symptomatic site or, if asymptomatic, on the most severely affected site as
      established by radiography; in all cases T1- and T2-weighted sequences in the
      axial, sagittal and coronal planes were acquired. RESULTS: Both the X-ray and MRI
      study revealed the typical alterations of ochronosis in the cases with a known
      diagnosis: articular space narrowing up to osseous ankylosis, calcifications,
      osteophytosis, reactive sclerosis of the articular surfaces; MRI was however more
      accurate in identifying the alterations and revealing lesions not visible at
      conventional radiology, such as ligament lesions. In the case of newly diagnosed
      ochronotic arthropathy MRI proved valuable for its ability to detect alterations
      that are poorly appreciable at conventional radiology. CONCLUSIONS: Modern
      diagnostic imaging, above all MRI, allowed us to identify the peculiar
      characteristic features of ochronosis and is fundamental both for the diagnosis
      and for differentiating ochronosis from other articular disorders.

PMID- 16292243
TI  - Endovascular treatment of benign superior vena cava syndrome: venographic
      patterns and implications for treatment.
AB  - PURPOSE: We report our experience with the percutaneous treatment of superior
      vena cava syndromes of benign etiology. MATERIALS AND METHODS: From August 1994
      to August 2003 a total of 14 superior vena cava syndromes of benign origin were
      treated. Previous use of a central venous catheter pending the development of a
      peripheral arteriovenous fistula for dialysis was believed to be the cause of the
      obstruction of the superior vena cava in 11 patients. In 2 other cases the cause
      was attributed to post-radiation mediastinal fibrosis and, in one case, to a
      previously implanted pacemaker. The superior vena cava syndrome was confirmed by
      venography. After negotiating the obstruction, a self-expanding stent was
      selected based on the CT and venographic data. At the end of the procedure,
      technical success was confirmed by venography, and haemodynamic success by
      pressure measurements. The follow-up allowed the assessment of the clinical
      success of the procedure. RESULTS: Technical success was achieved in 13 patients
      (92.8%); in one case the obstruction could not be negotiated with the wire guide,
      so the patient was referred for surgery. One self-expanding stent proved
      sufficient to resolve the central venous obstruction and restore superior vena
      cava diameter in all cases but one. In one young woman, whose central obstruction
      was resolved with PTA, was unable to complete the procedure with deployment of a
      self-expanding stent owing to a supervening asthma attack that could not be
      treated with the commonly-used drugs. No complications related to the procedure
      were reported. The symptoms cleared up within 2 weeks, and haemodynamic
      improvements were already seen within minutes of stent deployment. CONCLUSIONS:
      Percutaneous treatment is a valuable alternative to surgery as it is able to
      restore haemodynamic parameters and resolve the clinical picture, ensuring longer
      functionality to arteriovenous fistulae and an improved quality of life.

PMID- 16292244
TI  - Post-traumatic high flow priapism percutaneously treated with transcatheter
      embolisation.
AB  - PURPOSE: The aim of this paper is to present our experience in the percutaneous
      management of high-flow priapism with transcatheter embolisation and gelfoam.
      MATERIALS AND METHODS: We present three clinical cases in which an acute trauma
      caused the development of high-flow priapism. After differing initial management,
      all cases underwent arteriography, followed by demonstration of the arterial
      lacunar fistula and embolisation with gelfoam. RESULTS: Near immediate
      detumescence after the procedure confirmed the success of embolisation, which was
      supported by clinical and instrumental follow-up. DISCUSSION: In high-flow
      priapism, the best therapeutic solution remains transcatheter arterial
      embolisation, with ultra-selective catheterisation by microcatheter and
      embolisation of the pudendal artery only, which is responsible for the post
      traumatic arterial-lacunar fistula. This manoeuvre is not always technically
      easy, and requires experience and remarkable dexterity. Technical failure is
      always possible owing to the spasm of a peripheral arteriole that cannot be
      resolved with papaverine, and to the possible rehabilitation by the downstream
      contralateral circulation. Furthermore, the apprehension of the operator carrying
      out the procedure in this anatomical context may make the immediate result seem
      satisfactory, even if it is not optimal. All these considerations stress the need
      for a rigorous clinical and instrumental follow-up to guide later diagnostic and
      therapeutic choices.

PMID- 16292245
TI  - Lhermitte-Duclos disease: MR diffusion and spectroscopy.
AB  - AIM: To describe two cases of Lhermitte-Duclos disease studied with Diffusion MRI
      and MRi Spectroscopy. MATERIALS AND METHODS: Two patients showing a space
      occupying lesion in the cerebellar hemisphere were studied by conventional MRI
      associated with Diffusion MRI and Spectroscopy. RESULTS: Conventional MRI showed
      the typical morphological pattern of Lhermitte-Duclos disease with a slow-growing
      cerebellar mass mainly involving the cortex and non-enhancing thickened
      cerebellar folia. The mass exerted mild compression of the IV ventricle causing
      hydrocephalus On Diffusion imaging showed the lesion to be hyperintense due to
      residual T2-activity and hypointense on the ADC map. Spectroscopy was typical
      with an increased lactate peak and a reduced choline peak, indicating abnormal
      anaerobic glycolysis and demyelination, respectively. DISCUSSION: Lhermitte
      Duclos disease is a neurological condition which presents several signs and
      symptoms related to the cerebellar mass. Cowden's syndrome, an autosomal dominant
      neoplastic disorder with malignant features is associated in 40% of cases. MRI
      associated with functional examinations such as Diffusion Imaging and
      Spectroscopy is the imaging modality of choice in LDD patients. They allow a
      definite diagnosis as the neuroradiological findings correlate well with
      molecular biology theories regarding the malformative nature of dysplastic
      cerebellar gangliocytoma.

PMID- 16292247
TI  - Trends in HIV/AIDS diagnoses--33 states, 2001-2004.
AB  - In 2003, more than 1 million persons in the United States were estimated to be
      living with human immunodeficiency virus (HIV) infection. As a result of advances
      in treatment with highly active antiretroviral therapy (HAART) since 1996,
      persons infected with HIV are living longer than before and progression to
      acquired immunodeficiency syndrome (AIDS) has decreased. Consequently, AIDS
      surveillance no longer provides accurate population-based monitoring of the
      current HIV epidemic. Therefore, CDC recommends that all states and territories
      adopt confidential, name-based surveillance systems to report HIV infection. This
      report describes the characteristics of persons for whom HIV infection was
      diagnosed during 2001-2004 and reported to 33 state and local health departments
      with name-based HIV reporting. The findings indicate that the rate of HIV
      diagnosis in these states decreased among non-Hispanic blacks from 2001 to 2004;
      however, the rate of HIV diagnosis among blacks remained disproportionately high.
      In 2004, the rate among blacks was 8.4 times higher than among whites. Improved
      knowledge of HIV status and access to care and prevention services is important
      to decrease the number of new HIV infections among those populations most
      affected.

PMID- 16292246
TI  - Contraceptive use--United States and territories, Behavioral Risk Factor
      Surveillance System, 2002.
AB  - PROBLEM: Contraceptive use is an important determinant of unintended pregnancy.
      In the United States, approximately half of all pregnancies are unintended.
      Population-based information about contraceptive use patterns is limited at the
      state level. Information about contraceptive use for states can be used to guide
      the development of state programs and policies to decrease unintended pregnancy
      and the spread of sexually transmitted infections. Information about
      contraceptive use for specific subpopulations can be used to further refine state
      efforts to improve contraceptive use and subsequently decrease the occurrence of
      unintended pregnancy. REPORTING PERIOD: Data were collected in 2002 for men and
      women. DESCRIPTION OF SYSTEM: The Behavioral Risk Factor Surveillance System
      (BRFSS) is a random-digit--dialed, telephone survey of the noninstitutionalized
      U.S. population aged > or =18 years. All 50 states, the District of Columbia,
      Guam, the Commonwealth of Puerto Rico, and the U.S. Virgin Islands participated
      in BRFSS in 2002. These data can be used to track state progress towards the
      national health objectives for 2010 for responsible sexual behavior. The 2002
      BRFSS data represent the first time state data on contraceptive use in all 50
      states will be presented and examined by selected sociodemographic
      characteristics. The 2002 BRFSS also, for the first time, provided an opportunity
      to examine state-level contraceptive use patterns among men. RESULTS: Variation
      across states and territories was observed for the majority of contraceptive
      methods among the different demographics analyzed and among men and women. The
      percentage of men and women at risk for pregnancy who said they or their partner
      was using birth control was high overall and ranged from 67% (Guam) to 88%
      (Idaho). Oral contraceptives (i.e., the pill), vasectomy, tubal ligation, and
      condoms were the methods most frequently reported by both male and female
      respondents who said they or their partner was using birth control. Among female
      respondents using birth control, the pill was the most common method reported.
      Among men, vasectomy was the most commonly reported method. The prevalence of use
      for the four most commonly reported methods (pills, vasectomy, tubal ligation,
      condoms) varied as much as six-fold among states for vasectomy and three- to four
      fold for condoms, pills, and tubal ligation. INTERPRETATION: The findings in this
      report document substantial differences among states and sociodemographic groups
      within states in contraceptive method use. PUBLIC HEALTH ACTION: These data can
      help states identify populations with an unmet need for birth control, barriers
      to birth control use, and gaps in the range of birth control methods offered by
      health-care providers. An analysis of the prevalence of birth control use by
      state and selected population characteristics can help states target
      contraceptive programs to best meet the needs of their population.

PMID- 16292249
TI  - Immunization information system progress--United States, 2004.
AB  - One of the national health objectives for 2010 is to increase to at least 95% the
      proportion of children aged <6 years who participate in fully operational,
      population-based immunization registries (objective no. 14-26). Immunization
      registries are confidential, computerized information systems that collect and
      consolidate vaccination data from multiple health-care providers, generate
      reminder and recall notifications, and assess vaccination coverage within a
      defined geographic area. A registry with added capabilities, such as vaccine
      management, adverse event reporting, lifespan vaccination histories, and linkages
      with electronic data sources, is called an immunization information system (IIS).
      This report summarizes data from CDC's 2004 IIS Annual Report, a survey of 56
      grantees in 50 states, five cities, and the District of Columbia (DC) that
      receive funding under section 317b of the Public Health Service Act. The findings
      indicate that approximately 48% of U.S. children aged <6 years participated in an
      IIS. Moreover, 76% of public vaccination provider sites and 39% of private
      vaccination provider sites submitted immunization data to an IIS during the last
      6 months of 2004. Overcoming challenges and barriers to increasing the number of
      provider sites and the percentage of children aged <6 years participating in an
      IIS is critical to achieving the national health objective. CDC has developed a
      plan of action to address those challenges. Major components of the plan include,
      but are not limited to, a multiyear IIS business plan for each grantee and
      enhanced technical assistance to grantees with unresolved challenges.

PMID- 16292248
TI  - Cruise-ship--associated Legionnaires disease, November 2003-May 2004.
AB  - More than 9.4 million passengers traveled on pleasure cruises departing from
      North American ports in 2004, an increase of 13% since 2003 and 41% since 2001.
      Cruise ships typically transport closed populations of thousands of persons,
      often from diverse parts of the world. Travelers are at risk for becoming ill
      while on board, most commonly from person-to-person spread of viral
      gastrointestinal illnesses. Certain environmental organisms, such as Legionella
      spp., pose a risk to vulnerable passengers. During November 2003-May 2004, eight
      cases of Legionnaires disease (LD) among persons who had recently traveled on
      cruise ships were reported to CDC. This report describes these cases to raise
      clinician awareness of the potential for cruise-ship--associated LD and to
      emphasize the need for identification and reporting of cases to facilitate
      investigation.

PMID- 16292250
TI  - Lower extremity disease among persons aged > or =40 years with and without
      diabetes--United States, 1999-2002.
AB  - Lower extremity disease (LED), including peripheral arterial disease (PAD) and
      peripheral insensate neuropathy (PN), is a chronic condition that
      disproportionately affects older persons and persons with diabetes. LED can
      result in disabling foot complications (e.g., ulcers, infection, gangrene, or
      amputation). PAD has been associated with increased risk for cardiovascular
      morbidity and mortality. For this report, CDC analyzed data collected during 1999
      2002 from the National Health and Nutrition Examination Survey (NHANES) to update
      previously published estimates of the prevalence of LED among persons aged > or
      =40 years with and without diabetes. The results of this analysis indicated that
      approximately 18% of persons aged > or =40 years had LED and that LED was twice
      as prevalent among persons with diabetes as among those without diabetes.
      Approximately two thirds of persons with LED and half of those with both diabetes
      and LED were asymptomatic. Multiple complications of LED can be prevented if LED
      is detected early. Increasing knowledge among clinicians and the public of the
      prevalence of LED and associated risk factors might lead to early detection,
      intervention, and treatment to prevent disabling consequences.

PMID- 16292251
TI  - The carboxyl-terminal domain of inducible Hsp70 protects from ischemic injury in
      vivo and in vitro.
AB  - Heat shock protein (Hsp)70 can suppress both necrosis and apoptosis induced by
      various injuries in vivo and in vitro. However, the relative importance of
      different functions and binding partners of Hsp70 in ischemic protection is
      unknown. To explore this question, we tested the ability of Hsp70-K71E, an
      adenosine triphosphate (ATP)ase-deficient point mutant, and Hsp70-381-640, a
      deletion mutant lacking the ATPase domain and encoding the carboxyl-terminal
      portion, to protect against ischemia-like injury in vivo and in vitro. Heat shock
      protein 70-wild type (-WT), -K71E, -381-640, and control vector plasmid LXSN were
      expressed in primary murine astrocyte cultures. Astrocytes overexpressing Hsp70
      WT, -K71E, or -381-640 were all significantly protected from 4 h combined oxygen
      glucose deprivation and 24 h reperfusion when assessed by 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide assay or propidium iodide staining and cell
      counting (P < 0.05). Brains of rats were transfected with plasmids encoding Hsp70
      WT, -K71E, -381-640, or LXSN 24 h before 2 h middle cerebral artery occlusion
      followed by 24 h reperfusion. Animals that overexpressed either of the mutant
      proteins or Hsp70-WT had significantly better neurological scores and smaller
      infarcts than control animals. Protection by both mutants was associated with
      reduced protein aggregation, as assessed by ubiquitin immunohistochemistry and
      reduced nuclear translocation of apoptosis-inducing factor. The results show that
      the carboxyl-terminal portion of Hsp70 is sufficient for neuroprotection. This
      indicates that neither the ability to fold denatured proteins nor interactions
      with cochaperones or other proteins that bind the amino-terminal half of Hsp70
      are essential to ischemic protection.

PMID- 16292252
TI  - Establishing a photothrombotic 'ring' stroke model in adult mice with late
      spontaneous reperfusion: quantitative measurements of cerebral blood flow and
      cerebral protein synthesis.
AB  - This study sought to establish the photothrombotic 'ring' stroke model with late
      spontaneous reperfusion in adult mice. By applying a 3.0-mm diameter laser ring
      beam (514 nm, 0.21 mm thick, 0.65 W/cm2) onto the exposed skull for 60 secs with
      concurrent erythrosin B (4.25 mg/kg) intravenous infusion for 15 secs, the
      centrally located cortical region within the ring locus was progressively
      encroached by an annular ring-shaped perfusion deficit. In this region, local
      cerebral blood flow (lCBF) measured by laser-Doppler flowmetry declined promptly
      after irradiation to 43% of the baseline value at 30 mins poststroke. Using
      double tracer autoradiography, quantitative lCBF measured with
      [14C]iodoantipyrine was 46 to 17 to 58 ml/100 g/mins at 4 h to 48 h to 7 days
      postischemia in this area. Cerebral protein synthesis (CPS), as detected by
      [3H]leucine incorporation into protein, transiently decreased to 57% to 38% to
      112% at 4 h to 48 h to 7 days postischemia in the center region. Morphologically,
      some neurons in the center region appeared swollen at 4 h. At 48 h, the majority
      of neurons were severely swollen with eosinophilia and pyknosis, whereas at 7
      days poststroke' the tissue morphology became partly restored. The center within
      the mouse photothrombotic ring lesion thus exhibits reversible alterations of
      local CBF, CPS and tissue morphology that are reminiscent of the cortical
      penumbra in other models of focal cerebral ischemia.

PMID- 16292253
TI  - Fractal and noisy CBV dynamics in humans: influence of age and gender.
AB  - The complexity of spontaneous cerebral blood volume (CBV) fluctuations can emerge
      from random, fractal, or chaotic processes. Our aims were to define the
      contribution of these patterns to the observed complexity and to evaluate the
      effect of age and gender on it. The total hemoglobin content as the measure of
      CBV was monitored by near-infrared spectroscopy on volunteers (men n = 19, age =
      20 to 78 years; women n = 23, age = 21 to 79 years). Random and fractal patterns
      were distinguished by the spectral index (beta). Chaos was identified by
      surrogate analysis of the correlation dimension (a static chaotic parameter, the
      dimension of the correlation integral) and the largest Lyapunov exponent (a
      dynamic chaotic parameter, the rate of exponential divergence of the system
      states from a perturbed initial condition over the chaotic attractor). In
      spontaneous CBV fluctuations, both fast random and slow fractal dynamics are
      present separately in their spectra by a cutoff frequency, f'. Below f' the
      pattern is fractal, in that power rises inversely with frequency as 1/f(beta). f'
      decreases with age in men and women alike (F1: up to 0.12+/-0.06 Hz versus F2: up
      to 0.05+/-0.04 Hz at P = 0.015, and M1: up to 0.16+/-0.05 Hz versus M2: up to
      0.11+/-0.04 Hz at P = 0.044). Neither pre- nor postmenopausal age groups (1 and
      2, respectively) showed a (low)beta gender difference. Surrogate analysis showed
      that CBV dynamics cannot be characterized on the grounds of deterministic chaos.
      Cerebral blood volume fluctuates in a complex, bimodal manner in humans, in that
      the fast dynamics has no structure, while the slow dynamics exhibits a self
      similar, that is, fractal temporal structure. The range of fluctuation amplitudes
      produced by fractal dynamics is always larger than that of random fluctuations,
      and it shrinks with an altered structuring in aging women only.

PMID- 16292254
TI  - Present status of magnetic resonance imaging and spectroscopy in animal stroke
      models.
AB  - Magnetic resonance imaging (MRI) is based on a wide variety of physical
      parameters, which, in principle, can all influence the image contrast conditions.
      As these diverse variables are validated by independent physiological, metabolic,
      hemodynamic, and histological techniques, a physiological MRI evolves. This
      imaging modality has been successfully applied to experimental stroke studies,
      covering a broad range of raised questions. In the present review, we present an
      overview of possible physiological criteria to be studied by in vivo MRI and
      magnetic resonance spectroscopy, and critically analyze the present limits and
      future potential of the imaging technique for experimental stroke investigations.
      The documented applications cover the spectrum from morphological-structural
      details of the lesion to hemodynamic and metabolic alterations, inflammatory
      reaction, evaluation of thrombolytic treatment, studies on recovery of functional
      brain activation by functional MRI, and, finally, the most recent applications of
      exploring stem cells for regenerative therapy.

PMID- 16292256
TI  - Chaos-based communications at high bit rates using commercial fibre-optic links.
AB  - Chaotic signals have been proposed as broadband information carriers with the
      potential of providing a high level of robustness and privacy in data
      transmission. Laboratory demonstrations of chaos-based optical communications
      have already shown the potential of this technology, but a field experiment using
      commercial optical networks has not been undertaken so far. Here we demonstrate
      high-speed long-distance communication based on chaos synchronization over a
      commercial fibre-optic channel. An optical carrier wave generated by a chaotic
      laser is used to encode a message for transmission over 120 km of optical fibre
      in the metropolitan area network of Athens, Greece. The message is decoded using
      an appropriate second laser which, by synchronizing with the chaotic carrier,
      allows for the separation of the carrier and the message. Transmission rates in
      the gigabit per second range are achieved, with corresponding bit-error rates
      below 10(-7). The system uses matched pairs of semiconductor lasers as chaotic
      emitters and receivers, and off-the-shelf fibre-optic telecommunication
      components. Our results show that information can be transmitted at high bit
      rates using deterministic chaos in a manner that is robust to perturbations and
      channel disturbances unavoidable under real-world conditions.

PMID- 16292255
TI  - Early evolution of the venom system in lizards and snakes.
AB  - Among extant reptiles only two lineages are known to have evolved venom delivery
      systems, the advanced snakes and helodermatid lizards (Gila Monster and Beaded
      Lizard). Evolution of the venom system is thought to underlie the impressive
      radiation of the advanced snakes (2,500 of 3,000 snake species). In contrast, the
      lizard venom system is thought to be restricted to just two species and to have
      evolved independently from the snake venom system. Here we report the presence of
      venom toxins in two additional lizard lineages (Monitor Lizards and Iguania) and
      show that all lineages possessing toxin-secreting oral glands form a clade,
      demonstrating a single early origin of the venom system in lizards and snakes.
      Construction of gland complementary-DNA libraries and phylogenetic analysis of
      transcripts revealed that nine toxin types are shared between lizards and snakes.
      Toxinological analyses of venom components from the Lace Monitor Varanus varius
      showed potent effects on blood pressure and clotting ability, bioactivities
      associated with a rapid loss of consciousness and extensive bleeding in prey. The
      iguanian lizard Pogona barbata retains characteristics of the ancestral venom
      system, namely serial, lobular non-compound venom-secreting glands on both the
      upper and lower jaws, whereas the advanced snakes and anguimorph lizards
      (including Monitor Lizards, Gila Monster and Beaded Lizard) have more derived
      venom systems characterized by the loss of the mandibular (lower) or maxillary
      (upper) glands. Demonstration that the snakes, iguanians and anguimorphs form a
      single clade provides overwhelming support for a single, early origin of the
      venom system in lizards and snakes. These results provide new insights into the
      evolution of the venom system in squamate reptiles and open new avenues for
      biomedical research and drug design using hitherto unexplored venom proteins.

PMID- 16292263
TI  - Heavy weather.

PMID- 16292258
TI  - Origin of flight: Could 'four-winged' dinosaurs fly?
AB  - Our understanding of the origin of birds, feathers and flight has been greatly
      advanced by new discoveries of feathered non-avian dinosaurs, but functional
      analyses have not kept pace with taxonomic descriptions. Zhang and Zhou describe
      feathers on the tibiotarsus of a new basal enantiornithine bird from the Early
      Cretaceous of China. They infer, as did Xu and colleagues from similar feathers
      on the small non-avian theropod Microraptor found in similar deposits, that these
      leg feathers had aerodynamic properties and so might have been used in some kind
      of flight.

PMID- 16292264
TI  - Will the regulator please stand up.

PMID- 16292265
TI  - Pulling together.

PMID- 16292267
TI  - Stem-cell brothers divide.

PMID- 16292268
TI  - Japan's embryo experts beg for faster ethical reviews.

PMID- 16292269
TI  - Small conferences pay their way.

PMID- 16292270
TI  - US budget yields scant research rises.

PMID- 16292271
TI  - Day of judgement for intelligent design.

PMID- 16292272
TI  - Scheme to track greenhouse gases takes to the air.

PMID- 16292273
TI  - Atomic agency launches bid to bank nuclear fuel.

PMID- 16292276
TI  - Invasive species: shoot to kill.

PMID- 16292277
TI  - Climate change: the long-range forecast.

PMID- 16292278
TI  - Chinese students in the US: Taking a stand.

PMID- 16292280
TI  - How Wallace and Dampier faced tsunamis at sea.

PMID- 16292279
TI  - Wisdom of the crowd.

PMID- 16292281
TI  - Peer-review system could gain from author feedback.

PMID- 16292282
TI  - Intelligent, social rat can find joy in a hostile world.

PMID- 16292283
TI  - Space triumph reveals new spirit of openness in China.

PMID- 16292284
TI  - Biodiversity: involvement of local people is crucial.

PMID- 16292285
TI  - Climate proofing the Netherlands.

PMID- 16292286
TI  - Policy needs robust climate science.

PMID- 16292291
TI  - A polymath's dilemma.

PMID- 16292292
TI  - Epidemiology: dimensions of superspreading.

PMID- 16292293
TI  - Nano-optics: gold loses its lustre.

PMID- 16292294
TI  - Palaeontology: data on a plate.

PMID- 16292295
TI  - Developmental biology: the X-inactivation yo-yo.

PMID- 16292296
TI  - Communications technology: chaos down the line.

PMID- 16292298
TI  - Cell biology: two pores better than one?

PMID- 16292299
TI  - Environmental policy: regional commitment to reducing emissions.
AB  - The non-participation of the United States in the recently ratified Kyoto
      Protocol is a matter for global concern because it is estimated that the country
      produces 24% of all greenhouse-gas emissions worldwide. Here we analyse the
      commitment of individual states and municipalities to addressing this problem and
      find that, despite the federal policy, between 24 and 35% of the US population
      are currently (or soon will be) engaged in policies directed towards
      significantly reducing anthropogenic climate change. The importance of this sub
      national effort, which we estimate corresponds to 27-49% of the gross domestic
      product, will depend--like the targets adopted in Kyoto--on the real reductions
      achieved in greenhouse-gas emissions.

PMID- 16292300
TI  - Ant navigation: priming of visual route memories.
AB  - Ants travelling to and fro between their nest and a foraging area may follow
      stereotyped foodward and homeward routes that are guided by different visual and
      directional memory sequences. Honeybees are known to fly a feeder-to-hive or hive
      to-feeder vector according to whether or not they have recently fed--their
      feeding state controls which compass direction they select. We show here that the
      feeding state of the wood ant Formica rufa also determines the choice between an
      outward or inward journey, but by priming the selective retrieval of visual
      landmark memories.

PMID- 16292301
TI  - Potential impacts of a warming climate on water availability in snow-dominated
      regions.
AB  - All currently available climate models predict a near-surface warming trend under
      the influence of rising levels of greenhouse gases in the atmosphere. In addition
      to the direct effects on climate--for example, on the frequency of heatwaves-
      this increase in surface temperatures has important consequences for the
      hydrological cycle, particularly in regions where water supply is currently
      dominated by melting snow or ice. In a warmer world, less winter precipitation
      falls as snow and the melting of winter snow occurs earlier in spring. Even
      without any changes in precipitation intensity, both of these effects lead to a
      shift in peak river runoff to winter and early spring, away from summer and
      autumn when demand is highest. Where storage capacities are not sufficient, much
      of the winter runoff will immediately be lost to the oceans. With more than one
      sixth of the Earth's population relying on glaciers and seasonal snow packs for
      their water supply, the consequences of these hydrological changes for future
      water availability--predicted with high confidence and already diagnosed in some
      regions--are likely to be severe.

PMID- 16292302
TI  - Impact of regional climate change on human health.
AB  - The World Health Organisation estimates that the warming and precipitation trends
      due to anthropogenic climate change of the past 30 years already claim over
      150,000 lives annually. Many prevalent human diseases are linked to climate
      fluctuations, from cardiovascular mortality and respiratory illnesses due to
      heatwaves, to altered transmission of infectious diseases and malnutrition from
      crop failures. Uncertainty remains in attributing the expansion or resurgence of
      diseases to climate change, owing to lack of long-term, high-quality data sets as
      well as the large influence of socio-economic factors and changes in immunity and
      drug resistance. Here we review the growing evidence that climate-health
      relationships pose increasing health risks under future projections of climate
      change and that the warming trend over recent decades has already contributed to
      increased morbidity and mortality in many regions of the world. Potentially
      vulnerable regions include the temperate latitudes, which are projected to warm
      disproportionately, the regions around the Pacific and Indian oceans that are
      currently subjected to large rainfall variability due to the El Nino/Southern
      Oscillation sub-Saharan Africa and sprawling cities where the urban heat island
      effect could intensify extreme climatic events.

PMID- 16292304
TI  - A light-sensing knot revealed by the structure of the chromophore-binding domain
      of phytochrome.
AB  - Phytochromes are red/far-red light photoreceptors that direct photosensory
      responses across the bacterial, fungal and plant kingdoms. These include
      photosynthetic potential and pigmentation in bacteria as well as chloroplast
      development and photomorphogenesis in plants. Phytochromes consist of an amino
      terminal region that covalently binds a single bilin chromophore, followed by a
      carboxy-terminal dimerization domain that often transmits the light signal
      through a histidine kinase relay. Here we describe the three-dimensional
      structure of the chromophore-binding domain of Deinococcus radiodurans
      phytochrome assembled with its chromophore biliverdin in the Pr ground state. Our
      model, refined to 2.5 A resolution, reaffirms Cys 24 as the chromophore
      attachment site, locates key amino acids that form a solvent-shielded bilin
      binding pocket, and reveals an unusually formed deep trefoil knot that stabilizes
      this region. The structure provides the first three-dimensional glimpse into the
      photochromic behaviour of these photoreceptors and helps to explain the evolution
      of higher plant phytochromes from prokaryotic precursors.

PMID- 16292303
TI  - Structure of the E. coli protein-conducting channel bound to a translating
      ribosome.
AB  - Secreted and membrane proteins are translocated across or into cell membranes
      through a protein-conducting channel (PCC). Here we present a cryo-electron
      microscopy reconstruction of the Escherichia coli PCC, SecYEG, complexed with the
      ribosome and a nascent chain containing a signal anchor. This reconstruction
      shows a messenger RNA, three transfer RNAs, the nascent chain, and detailed
      features of both a translocating PCC and a second, non-translocating PCC bound to
      mRNA hairpins. The translocating PCC forms connections with ribosomal RNA
      hairpins on two sides and ribosomal proteins at the back, leaving a frontal
      opening. Normal mode-based flexible fitting of the archaeal SecYEbeta structure
      into the PCC electron microscopy densities favours a front-to-front arrangement
      of two SecYEG complexes in the PCC, and supports channel formation by the opening
      of two linked SecY halves during polypeptide translocation. On the basis of our
      observation in the translocating PCC of two segregated pores with different
      degrees of access to bulk lipid, we propose a model for co-translational protein
      translocation.

PMID- 16292305
TI  - The formation of stars by gravitational collapse rather than competitive
      accretion.
AB  - There are two dominant models of how stars form. Under gravitational collapse,
      star-forming molecular clumps, of typically hundreds to thousands of solar masses
      (M(o)), fragment into gaseous cores that subsequently collapse to make individual
      stars or small multiple systems. In contrast, competitive accretion theory
      suggests that at birth all stars are much smaller than the typical stellar mass
      (approximately 0.5M(o)), and that final stellar masses are determined by the
      subsequent accretion of unbound gas from the clump. Competitive accretion models
      interpret brown dwarfs and free-floating planets as protostars ejected from star
      forming clumps before they have accreted much mass; key predictions of this model
      are that such objects should lack disks, have high velocity dispersions, form
      more frequently in denser clumps, and that the mean stellar mass should vary
      within the Galaxy. Here we derive the rate of competitive accretion as a function
      of the star-forming environment, based partly on simulation, and determine in
      what types of environments competitive accretion can occur. We show that no
      observed star-forming region can undergo significant competitive accretion, and
      that the simulations that show competitive accretion do so because the assumed
      properties differ from those determined by observation. Our result shows that
      stars form by gravitational collapse, and explains why observations have failed
      to confirm predictions of the competitive accretion model.

PMID- 16292307
TI  - Spin-torque diode effect in magnetic tunnel junctions.
AB  - There is currently much interest in the development of 'spintronic' devices, in
      which harnessing the spins of electrons (rather than just their charges) is
      anticipated to provide new functionalities that go beyond those possible with
      conventional electronic devices. One widely studied example of an effect that has
      its roots in the electron's spin degree of freedom is the torque exerted by a
      spin-polarized electric current on the spin moment of a nanometre-scale magnet.
      This torque causes the magnetic moment to rotate at potentially useful
      frequencies. Here we report a very different phenomenon that is also based on the
      interplay between spin dynamics and spin-dependent transport, and which arises
      from unusual diode behaviour. We show that the application of a small radio
      frequency alternating current to a nanometre-scale magnetic tunnel junction can
      generate a measurable direct-current (d.c.) voltage across the device when the
      frequency is resonant with the spin oscillations that arise from the spin-torque
      effect: at resonance (which can be tuned by an external magnetic field), the
      structure exhibits different resistance states depending on the direction of the
      current. This behaviour is markedly different from that of a conventional
      semiconductor diode, and could form the basis of a nanometre-scale radio
      frequency detector in telecommunication circuits.

PMID- 16292306
TI  - Nanofabricated media with negative permeability at visible frequencies.
AB  - A great deal of attention has recently been focused on a new class of smart
      materials--so-called left-handed media--that exhibit highly unusual
      electromagnetic properties and promise new device applications. Left-handed
      materials require negative permeability micro, an extreme condition that has so
      far been achieved only for frequencies in the microwave to terahertz range.
      Extension of the approach described in ref. 7 to achieve the necessary high
      frequency magnetic response in visible optics presents a formidable challenge, as
      no material--natural or artificial--is known to exhibit any magnetism at these
      frequencies. Here we report a nanofabricated medium consisting of
      electromagnetically coupled pairs of gold dots with geometry carefully designed
      at a 10-nm level. The medium exhibits a strong magnetic response at visible-light
      frequencies, including a band with negative micro. The magnetism arises owing to
      the excitation of an antisymmetric plasmon resonance. The high-frequency
      permeability qualitatively reveals itself via optical impedance matching. Our
      results demonstrate the feasibility of engineering magnetism at visible
      frequencies and pave the way towards magnetic and left-handed components for
      visible optics.

PMID- 16292308
TI  - Global pattern of trends in streamflow and water availability in a changing
      climate.
AB  - Water availability on the continents is important for human health, economic
      activity, ecosystem function and geophysical processes. Because the saturation
      vapour pressure of water in air is highly sensitive to temperature, perturbations
      in the global water cycle are expected to accompany climate warming. Regional
      patterns of warming-induced changes in surface hydroclimate are complex and less
      certain than those in temperature, however, with both regional increases and
      decreases expected in precipitation and runoff. Here we show that an ensemble of
      12 climate models exhibits qualitative and statistically significant skill in
      simulating observed regional patterns of twentieth-century multidecadal changes
      in streamflow. These models project 10-40% increases in runoff in eastern
      equatorial Africa, the La Plata basin and high-latitude North America and
      Eurasia, and 10-30% decreases in runoff in southern Africa, southern Europe, the
      Middle East and mid-latitude western North America by the year 2050. Such changes
      in sustainable water availability would have considerable regional-scale
      consequences for economies as well as ecosystems.

PMID- 16292309
TI  - Palaeoanatomy and biological affinities of a Cambrian deuterostome (Stylophora).
AB  - Stylophora are a peculiar extinct group of asymmetrical deuterostomes whose
      biological affinity has been fiercely debated. Disarticulated skeletal elements
      of a ceratocystid stylophoran recovered from the earliest Middle Cambrian of
      Morocco are not only the oldest stylophorans in the fossil record, but their
      exceptional preservation provides crucial data on the microstructure of its
      skeleton. Stylophoran plates are constructed of a three-dimensional mesh, termed
      'stereom', identical to that of living echinoderms in which stereom
      microstructure provides a reliable guide to the nature of the investing soft
      tissues. Using modern echinoderm anatomy to interpret stereom microstructure of
      stylophoran elements, here we show that the large proximal lumen of their
      appendage was filled with muscle and that ligamentary tissues bound distal
      elements firmly together. We find no evidence for a mouth in the proximal lumen
      and no evidence that the covering plates of the appendage were articulated. Thus,
      although skeletal structure suggests that stylophorans are echinoderms, their
      appendage was not a feeding arm but a muscular locomotory organ.

PMID- 16292310
TI  - Superspreading and the effect of individual variation on disease emergence.
AB  - Population-level analyses often use average quantities to describe heterogeneous
      systems, particularly when variation does not arise from identifiable groups. A
      prominent example, central to our current understanding of epidemic spread, is
      the basic reproductive number, R(0), which is defined as the mean number of
      infections caused by an infected individual in a susceptible population.
      Population estimates of R(0) can obscure considerable individual variation in
      infectiousness, as highlighted during the global emergence of severe acute
      respiratory syndrome (SARS) by numerous 'superspreading events' in which certain
      individuals infected unusually large numbers of secondary cases. For diseases
      transmitted by non-sexual direct contacts, such as SARS or smallpox, individual
      variation is difficult to measure empirically, and thus its importance for
      outbreak dynamics has been unclear. Here we present an integrated theoretical and
      statistical analysis of the influence of individual variation in infectiousness
      on disease emergence. Using contact tracing data from eight directly transmitted
      diseases, we show that the distribution of individual infectiousness around R(0)
      is often highly skewed. Model predictions accounting for this variation differ
      sharply from average-based approaches, with disease extinction more likely and
      outbreaks rarer but more explosive. Using these models, we explore implications
      for outbreak control, showing that individual-specific control measures
      outperform population-wide measures. Moreover, the dramatic improvements achieved
      through targeted control policies emphasize the need to identify predictive
      correlates of higher infectiousness. Our findings indicate that superspreading is
      a normal feature of disease spread, and to frame ongoing discussion we propose a
      rigorous definition for superspreading events and a method to predict their
      frequency.

PMID- 16292311
TI  - Specification of astrocytes by bHLH protein SCL in a restricted region of the
      neural tube.
AB  - Astrocytes are the most abundant and functionally diverse glial population in the
      vertebrate central nervous system (CNS). However, the mechanisms underlying
      astrocyte specification are poorly understood. It is well established that
      cellular diversification of neurons in the embryo is generated by position
      dependent extrinsic signals and combinatorial interactions of transcription
      factors that direct specific cell fates by suppressing alternative fates. It is
      unknown whether a comparable process determines embryonic astrocyte identity.
      Indeed, astrocyte development is generally thought to take place in a position
      independent manner. Here we show multiple functions of Stem cell leukaemia (Scl,
      also known as Tal1), which encodes a basic helix-loop-helix (bHLH) transcription
      factor, in the regulation of both astrocyte versus oligodendrocyte cell fate
      acquisition and V2b versus V2a interneuron cell fate acquisition in the p2 domain
      of the developing vertebrate spinal cord. Our findings demonstrate a regionally
      restricted transcriptional programme necessary for astrocyte and V2b interneuron
      development, with striking parallels to the involvement of SCL in haematopoiesis.
      They further indicate that acquisition of embryonic glial subtype identity might
      be regulated by genetic interactions between SCL and the transcription factor
      Olig2 in the ventral neural tube.

PMID- 16292312
TI  - Control of B-cell responses by Toll-like receptors.
AB  - Toll-like receptors (TLRs) detect microbial infection and have an essential role
      in the induction of immune responses. TLRs can directly induce innate host
      defence responses, but the mechanisms of TLR-mediated control of adaptive
      immunity are not fully understood. Although TLR-induced dendritic cell maturation
      is required for activation of T-helper (T(H)) cells, the role of TLRs in B-cell
      activation and antibody production in vivo is not yet known. Here we show that
      activation and differentiation of T(H) cells is not sufficient for the induction
      of T-dependent B-cell responses. We find that, in addition to CD4+ T-cell help,
      generation of T-dependent antigen-specific antibody responses requires activation
      of TLRs in B cells.

PMID- 16292313
TI  - A histone H3 methyltransferase controls epigenetic events required for meiotic
      prophase.
AB  - Epigenetic modifications of histones regulate gene expression and chromatin
      structure. Here we show that Meisetz (meiosis-induced factor containing a PR/SET
      domain and zinc-finger motif) is a histone methyltransferase that is important
      for the progression of early meiotic prophase. Meisetz transcripts are detected
      only in germ cells entering meiotic prophase in female fetal gonads and in
      postnatal testis. Notably, Meisetz has catalytic activity for trimethylation, but
      not mono- or dimethylation, of lysine 4 of histone H3, and a transactivation
      activity that depends on its methylation activity. Mice in which the Meisetz gene
      is disrupted show sterility in both sexes due to severe impairment of the double
      stranded break repair pathway, deficient pairing of homologous chromosomes and
      impaired sex body formation. In Meisetz-deficient testis, trimethylation of
      lysine 4 of histone H3 is attenuated and meiotic gene transcription is altered.
      These findings indicate that meiosis-specific epigenetic events in mammals are
      crucial for proper meiotic progression.

PMID- 16292315
TI  - Force production by disassembling microtubules.
AB  - Microtubules (MTs) are important components of the eukaryotic cytoskeleton: they
      contribute to cell shape and movement, as well as to the motions of organelles
      including mitotic chromosomes. MTs bind motor enzymes that drive many such
      movements, but MT dynamics can also contribute to organelle motility. Each MT
      polymer is a store of chemical energy that can be used to do mechanical work, but
      how this energy is converted to motility remains unknown. Here we show, by
      conjugating glass microbeads to tubulin polymers through strong inert linkages,
      such as biotin-avidin, that depolymerizing MTs exert a brief tug on the beads, as
      measured with laser tweezers. Analysis of these interactions with a molecular
      mechanical model of MT structure and force production shows that a single
      depolymerizing MT can generate about ten times the force that is developed by a
      motor enzyme; thus, this mechanism might be the primary driving force for
      chromosome motion. Because even the simple coupler used here slows MT
      disassembly, physiological couplers may modulate MT dynamics in vivo.

PMID- 16292314
TI  - Chromatin remodelling at a DNA double-strand break site in Saccharomyces
      cerevisiae.
AB  - The repair of DNA double-strand breaks (DSBs) is crucial for maintaining genome
      stability. Eukaryotic cells repair DSBs by both non-homologous end joining and
      homologous recombination. How chromatin structure is altered in response to DSBs
      and how such alterations influence DSB repair processes are important issues. In
      vertebrates, phosphorylation of the histone variant H2A.X occurs rapidly after
      DSB formation, spreads over megabase chromatin domains, and is required for
      stable accumulation of repair proteins at damage foci. In Saccharomyces
      cerevisiae, phosphorylation of the two principal H2A species is also signalled by
      DSB formation, which spreads approximately 40 kb in either direction from the
      DSB. Here we show that near a DSB phosphorylation of H2A is followed by loss of
      histones H2B and H3 and increased sensitivity of chromatin to digestion by
      micrococcal nuclease; however, phosphorylation of H2A and nucleosome loss occur
      independently. The DNA damage sensor MRX is required for histone loss, which also
      depends on INO80, a nucleosome remodelling complex. The repair protein Rad51
      (ref. 6) shows delayed recruitment to DSBs in the absence of histone loss,
      suggesting that MRX-dependent nucleosome remodelling regulates the accessibility
      of factors directly involved in DNA repair by homologous recombination. Thus, MRX
      may regulate two pathways of chromatin changes: nucleosome displacement for
      efficient recruitment of homologous recombination proteins; and phosphorylation
      of H2A, which modulates checkpoint responses to DNA damage.

PMID- 16292317
TI  - Big dynorphin, a prodynorphin-derived peptide produces NMDA receptor-mediated
      effects on memory, anxiolytic-like and locomotor behavior in mice.
AB  - Effects of big dynorphin (Big Dyn), a prodynorphin-derived peptide consisting of
      dynorphin A (Dyn A) and dynorphin B (Dyn B) on memory function, anxiety, and
      locomotor activity were studied in mice and compared to those of Dyn A and Dyn B.
      All peptides administered i.c.v. increased step-through latency in the passive
      avoidance test with the maximum effective doses of 2.5, 0.005, and 0.7
      nmol/animal, respectively. Effects of Big Dyn were inhibited by MK 801 (0.1
      mg/kg), an NMDA ion-channel blocker whereas those of dynorphins A and B were
      blocked by the kappa-opioid antagonist nor-binaltorphimine (6 mg/kg). Big Dyn
      (2.5 nmol) enhanced locomotor activity in the open field test and induced
      anxiolytic-like behavior both effects blocked by MK 801. No changes in locomotor
      activity and no signs of anxiolytic-like behavior were produced by dynorphins A
      and B. Big Dyn (2.5 nmol) increased time spent in the open branches of the
      elevated plus maze apparatus with no changes in general locomotion. Whereas
      dynorphins A and B (i.c.v., 0.05 and 7 nmol/animal, respectively) produced
      analgesia in the hot-plate test Big Dyn did not. Thus, Big Dyn differs from its
      fragments dynorphins A and B in its unique pattern of memory enhancing, locomotor
      and anxiolytic-like effects that are sensitive to the NMDA receptor blockade.
      The findings suggest that Big Dyn has its own function in the brain different
      from those of the prodynorphin-derived peptides acting through kappa-opioid
      receptors.

PMID- 16292318
TI  - Involvement of kappa/dynorphin system in WIN 55,212-2 self-administration in
      mice.
AB  - Self-administration procedures have not yet provided evidence that freely moving
      mice can reliably acquire and maintain an operant behavior to self-administer
      cannabinoid agonists. The aim of the present work was to establish a model of
      cannabinoid operant intravenous self-administration in freely moving mice given
      the relevance of this species for the use of genetically modified animals. In
      addition, the possible involvement of the kappa/dynorphin system in cannabinoid
      self-administration was evaluated by using pro-dynorphin knockout mice. Outbred
      CD1 wild-type mice as well as pro-dynorphin knockout and wild-type mice were
      trained to self-administer the cannabinoid receptor agonist WIN 55,212-2 under an
      FR1 schedule of reinforcement. Two cannabinoid training doses (6.25 and 12.5
      microg/kg/infusion) were used in the acquisition studies in outbred mice. Animals
      acquired a reliable operant responding to self-administer WIN 55,212-2 (12.5
      microg/kg/infusion), but required as many as 15 sessions to attain this behavior.
      Interestingly, when a previous injection of WIN 55,212-2 (0.1 mg/kg, i.p.) was
      administered in the home-cage 24 h before the first session, mice acquired
      operant responding for cannabinoid self-administration by the fourth session.
      When the kappa-opioid agonist antagonist nor-binaltorphimine (5 mg/kg s.c.) was
      administered 4 h before the first session, the time required to acquire a
      reliable cannabinoid self-administration was also significantly reduced. Finally,
      a shift to the left in the dose-intake curve to self-administer WIN 55,212-2 was
      observed in pro-dynorphin knockout mice when compared to wild-type mice. These
      results indicate that the activation of the kappa/dynorphin opioid system after
      WIN 55,212-2 administration could counteract cannabinoid rewarding effects.

PMID- 16292319
TI  - Raloxifene treatment enhances brain activation during recognition of familiar
      items: a pharmacological fMRI study in healthy elderly males.
AB  - Raloxifene is a selective estrogen receptor modulator that may delay the onset of
      mild cognitive impairment in elderly women. Effects of raloxifene treatment on
      mental performance in males remain to be investigated. In a previous functional
      magnetic resonance imaging (fMRI) study, we showed that raloxifene treatment
      enhanced brain activation in elderly males during encoding of new information
      (faces) into memory. The current study used fMRI in the same group of subjects to
      screen for effects of raloxifene treatment on brain function during face
      recognition. Healthy elderly males (n=28; mean age 63.6 years, SD 2.4) were
      scanned at baseline and after 3 months of treatment with either raloxifene 120 mg
      (n=14) or placebo (n=14) in a randomized, double-blind, placebo-controlled study
      design. Functional data were analyzed in an event-related fashion with respect to
      correct hits and correct rejections using FSL software. Performance data were
      analyzed with respect to recognition accuracy, latency, and response bias.
      Functional effects of treatment were found on brain activation related to correct
      hits only. When compared to placebo treatment, raloxifene treatment enhanced
      brain activation in the left posterior parahippocampal area (Z=3.9) and right
      inferior prefrontal cortex (Z=3.5). Recognition accuracy scores remained stable
      in the raloxifene group, whereas the placebo group showed a small but significant
      decrease in accuracy scores (p=0.02). No significant effects were found on
      response bias or latency. In conclusion, raloxifene treatment affects brain
      function during memory performance in a way that may reflect increased arousal
      during initial encoding, with downstream effects on brain function during
      retrieval of information. Behaviorally, such neurofunctional effects may actively
      block decreased memory performance as a result of context-dependency. The
      validity of these predictions can be tested in large-scale clinical trials.

PMID- 16292320
TI  - Region-specific effects of nicotine on brain activity: a pharmacological MRI
      study in the drug-naive rat.
AB  - We have applied pharmacological magnetic resonance imaging (phMRI) methods to map
      the functional response to nicotine in drug-naive rats. Nicotine (0.35 mg/kg
      intravenous (i.v.)) increased relative cerebral blood volume (rCBV) in cortical
      (including medial prefrontal, cingulate orbitofrontal, insular) and subcortical
      (including amygdala and dorsomedial hippocampus) structures. The pharmacological
      specificity of the effect was demonstrated by acute pretreatment with the
      nicotinic acetylcholine receptor (nAChR) ion-channel-blocking agent mecamylamine,
      which suppressed the rCBV response to nicotine. Control experiments with
      norepinephrine, a potent non-brain-penetrant vasopressor, at a dose that mimics
      the cardiovascular response induced by nicotine were performed to assess the
      potential confounding effects of peripheral blood pressure changes induced by
      nicotine. In an attempt to highlight the relative contribution of different nAChR
      subtypes to the observed activation pattern of nicotine, we also investigated the
      central phMRI response to an acute challenge with (R)-N-(1-azabicyclo[2.2.2]oct-3
      yl)(5-(2-pyridyl)thiophene-2-carboxamide) (cpdA, at 5, 10, 20, and 30 mg/kg i.v.)
      and 5-iodo-A-85380 (5IA, 5 mg/kg i.v.). CpdA is a selective agonist at homomeric
      alpha7 nAChRs, while 5IA features high in vivo affinity for the alpha4beta2* and
      other less-abundant beta2-containing nicotinic receptors. CpdA did not produce
      significant rCBV changes at any of the doses tested, whereas 5IA induced a
      pattern of activation very similar to that induced by nicotine. The lack of phMRI
      response to cpdA together with the high spatial overlap between the activation
      profile of nicotine and 5IA, suggest that the acute functional response to
      nicotine in drug-naive rats is mediated by beta2-containing nAChR isoforms,
      presumably belonging to the alpha4beta2* subtype.

PMID- 16292322
TI  - Elevated impulsivity and impaired decision-making in abstinent Ecstasy (MDMA)
      users compared to polydrug and drug-naive controls.
AB  - Ecstasy (MDMA; 3,4-methylenedioxymethamphetamine) has a well-recognized
      neurotoxic effect on central serotonergic (5-HT) systems in animals, and there is
      some evidence of persistent serotonergic dysregulation in human ecstasy users.
      Serotonin is believed to mediate impulsive behavior and effective decision
      making. Thus, the aim of the present study was to investigate impulsive behavior
      and decision-making in abstinent regular ecstasy users. Three groups were
      compared: 'ecstasy users' (recreational ecstasy users who reported modest use of
      illicit drugs other than cannabis), 'polydrug controls' (ecstasy naive illicit
      drug users), and 'drug-naive controls'. All participants completed personal
      details and general drug history questionnaires, the National Adult Reading Test,
      Matching Familiar Figures Test (MFF20), a risky decision-making task (RDMT), and
      the Card Arranging Reward Responsivity Objective Test (CARROT). The groups did
      not differ on the CARROT measure of responsiveness to financial incentive;
      however, the ecstasy group displayed significantly elevated MFF20 impulsivity,
      and showed reduced discrimination between magnitudes of prospective gains and
      losses when making risky decisions, compared to the 'polydrug' and 'drug-naive'
      control groups. These findings may reflect a vulnerability of 5-HT systems in the
      orbital prefrontal cortex and interconnected corticolimbic circuitry to the
      cumulative neurotoxic effects of ecstasy and have clinical significance for
      regular ecstasy users. The combination of elevated impulsivity and impaired use
      of reinforcement cues in uncertain decision-making may comprise risk factors for
      continued drug abuse and everyday functioning.

PMID- 16292321
TI  - The alpha2-adrenoceptor antagonist dexefaroxan enhances hippocampal neurogenesis
      by increasing the survival and differentiation of new granule cells.
AB  - The generation of new neurons in the hippocampus is a dynamic process regulated
      by environmental, endocrine, and pharmacological factors. Since enhancement of
      hippocampal neurogenesis has been associated with learning and memory, and the
      locus coeruleus-noradrenergic system has been shown to modulate these cognitive
      functions, we hypothesized that activation of noradrenergic neurotransmission
      might enhance neurogenesis in the adult hippocampus. To test this hypothesis in
      vivo, we induced the release of noradrenaline in the hippocampus by blocking
      presynaptic inhibitory autoreceptors with the selective alpha2-adrenoceptor
      antagonist dexefaroxan. Confocal microscopy showed that noradrenergic afferents
      make contact with proliferating and differentiating cells, suggesting a direct
      noradrenergic influence on neurogenesis. Chronic systemic treatment of rats with
      dexefaroxan did not affect cell proliferation per se in the dentate gyrus (as
      monitored by bromodeoxyuridine-labeling), but promoted the long-term survival of
      newborn neurons by reducing apoptosis. Dexefaroxan treatment also enhanced the
      number and complexity of the dendritic arborizations of polysialated neural cell
      adhesion molecule-positive neurons. The trophic effects of dexefaroxan on newborn
      cells might involve an increase in brain-derived neurotrophic factor, which was
      upregulated in afferent noradrenergic fiber projection areas and in neurons in
      the granule cell layer. By promoting the survival of new endogenously formed
      neurons, dexefaroxan treatment represents a potential therapeutic strategy for
      maintaining adult neurogenesis in neurodegenerative conditions, such as
      Alzheimer's disease, that affect the hippocampus.

PMID- 16292323
TI  - Neurochemical effects of olanzapine in first-hospitalization manic adolescents: a
      proton magnetic resonance spectroscopy study.
AB  - We used proton magnetic resonance spectroscopy (1H MRS) to compare the in vivo
      effects of olanzapine on prefrontal N-acetyl-aspartate (NAA) levels in treatment
      remitters and nonremitters. Secondary aims of this study were to identify
      neurochemical predictors of successful olanzapine treatment and other
      neurochemical effects of olanzapine. In all, 20 adolescents admitted for their
      first hospitalization for bipolar disorder, type I, manic or mixed and 10
      demographically matched healthy subjects were recruited. Manic adolescents were
      treated with olanzapine monotherapy and scanned at three time points (N = 19).
      Medial and left and right lateral ventral prefrontal NAA, choline,
      creatine/phosphocreatine, myo-inositol, and glutamate/glutamine were measured at
      baseline, prior to receiving medication, and on days 7 and 28 of treatment.
      Healthy subjects did not receive medication but underwent 1H MRS scans at the
      same time points to assess for normal variability in metabolites over time.
      Although there was no overall increase in NAA in manic adolescents following 28
      days of treatment with olanzapine, olanzapine remitters (N = 11, 58%) exhibited a
      greater increase in medial ventral prefrontal NAA compared with nonremitters (N =
      8, 42%, p = 0.006). Specifically, from baseline to end point, NAA levels
      decreased in nonremitters (p = 0.03) and increased in remitters (p = 0.05). Manic
      adolescents treated with olanzapine had an increase from baseline to day 7 in
      medial (p = 0.002) and right lateral (p = 0.02) ventral prefrontal choline.
      Baseline medial ventral prefrontal choline was greater in olanzapine remitters
      than in nonremitters (p = 0.001). Successful treatment of mania with olanzapine
      may lead to increased ventral prefrontal neuronal viability and/or function as
      compared to unsuccessful treatment with olanzapine. Additionally, olanzapine
      induced increases in choline may lead to alteration of abnormalities in cell
      membrane metabolism or second messenger pathways that are thought to be involved
      in the pathophysiology of bipolar disorder.

PMID- 16292324
TI  - Effects of atypical antipsychotic drugs on intralipid intake and cocaine-induced
      hyperactivity in rats.
AB  - Clozapine and olanzapine have been shown to acutely stimulate consumption of a
      fat emulsion (Intralipid) by male Lister hooded rats. We initially investigated
      the extent of any sex difference in Intralipid hyperphagia associated with
      olanzapine treatment. We then examined the degree of Intralipid hyperphagia
      produced by a range of atypical antipsychotic drugs having different associations
      with human weight gain, and also determined their effects on cocaine-stimulated
      locomotor activity as a measure of functional dopamine antagonism in vivo.
      Olanzapine (0.1-1 mg/kg) stimulated Intralipid intake to an equal extent in male
      and female rats. Quetiapine (10 mg/kg) also stimulated Intralipid intake whereas
      ziprasidone (0.3-10 mg/kg) or risperidone (0.03-0.3 mg/kg) did not have this
      effect. All of the compounds, except quetiapine, reduced cocaine-stimulated
      locomotor activity but the relationship to the degree of Intralipid hyperphagia
      was variable. Since there was a positive relationship between Intralipid
      hyperphagia and the reported extent of human body weight gain, we conclude that
      Intralipid hyperphagia may have predictive value for this drug-associated side
      effect and is not related to the dopamine antagonist properties of these agents.

PMID- 16292325
TI  - Homeostatic regulation of sleep in a genetic model of depression in the mouse:
      effects of muscarinic and 5-HT1A receptor activation.
AB  - In depressed patients, sleep undergoes marked alterations, especially sleep onset
      insomnia, sleep fragmentation, and disturbances of the Rapid Eye Movement (REM)
      sleep. Abnormalities of rest-activity rhythms and of hypothalamic-pituitary
      adrenocortical function have also been described in these patients. In the
      present study, we examined the presence of such abnormalities in a recently
      developed line of mice (Helpless mice-H) that exhibit depression-like behaviors
      in validated tests, compared to the nonhelpless (NH) line derived from the same
      colony. Experiments were essentially carried out in females for which previous
      studies showed marked differences between H and NH lines. Compared to NH mice,
      the H line exhibited (i) lower basal locomotor activity, (ii) sleep
      fragmentation, shift towards lighter sleep stages, and facilitation of REM sleep
      reflected by increased amounts and decreased latency, (iii) larger response to
      the REM sleep promoting effect of muscarinic receptor stimulation (by arecoline).
      In contrast, H and NH mice were equally responsive to the REM sleep inhibitory
      effect of 5-HT1A receptor stimulation (by 8-OH-DPAT). In addition, a deficiency
      in delta power enhancement after sleep deprivation was observed in the H group,
      and acute immobilization stress in this group failed to elicit a REM sleep
      rebound and was associated with a long-lasting raise in serum corticosterone
      levels. These results further validate H mice as a depression model and suggest
      they might be of particular interest for investigating the neurobiological
      mechanisms and possibly genetic substrates underlying sleep alterations
      associated with depression.

PMID- 16292326
TI  - Patterns of gene expression in the frontal cortex discriminate alcoholic from
      nonalcoholic individuals.
AB  - Alcohol dependence is characterized by tolerance, physical dependence, and
      craving. The neuroadaptations underlying these effects of chronic alcohol abuse
      are likely due to altered gene expression. Previous gene expression studies using
      human post-mortem brain demonstrated that several gene families were altered by
      alcohol abuse. However, most of these changes in gene expression were small. It
      is not clear if gene expression profiles have sufficient power to discriminate
      control from alcoholic individuals and how consistent gene expression changes are
      when a relatively large sample size is examined. In the present study, microarray
      analysis (approximately 47,000 elements) was performed on the superior frontal
      cortex of 27 individual human cases (14 well characterized alcoholics and 13
      matched controls). A partial least squares statistical procedure was applied to
      identify genes with altered expression levels in alcoholics. We found that genes
      involved in myelination, ubiquitination, apoptosis, cell adhesion, neurogenesis,
      and neural disease showed altered expression levels. Importantly, genes involved
      in neurodegenerative diseases such as Alzheimer's disease were significantly
      altered suggesting a link between alcoholism and other neurodegenerative
      conditions. A total of 27 genes identified in this study were previously shown to
      be changed by alcohol abuse in previous studies of human post-mortem brain. These
      results revealed a consistent re-programming of gene expression in alcohol
      abusers that reliably discriminates alcoholic from non-alcoholic individuals.

PMID- 16292328
TI  - Hallucinogen-induced UP states in the brain slice of rat prefrontal cortex: role
      of glutamate spillover and NR2B-NMDA receptors.
AB  - Psychedelic hallucinogens (eg LSD or DOI) induce disturbances of mood,
      perception, and cognition through stimulation of serotonin 5-HT2A receptors.
      While these drugs are not proconvulsant, they have been shown by microdialysis to
      increase extracellular glutamate in the prefrontal cortex. Electrophysiological
      studies in the rat prefrontal slice have shown that both LSD and DOI enhance a
      prolonged, late wave of glutamate release onto layer V pyramidal neurons after an
      electrical stimulus. Here, we hypothesize that the network activity underlying
      this UP state involves glutamate spillover from excitatory synapses. To test this
      hypothesis, we raised the viscosity of the extracellular solution by adding the
      inert macromolecule dextran (approximately 1 mM) that is known to retard
      glutamate overflow into the extrasynaptic space. Dextran suppressed the UP state
      or late excitatory postsynaptic current (EPSC), but neither the fast EPSC, the
      traditional polysynaptic EPSC, nor a synaptic form of 5-HT2A-mediated
      transmission (serotonin-induced spontaneous EPSCs). Consistent with the previous
      work showing that extrasynaptic glutamate transmission in adult depends on NR2B
      containing NMDA receptors, we found that NR2B-selective antagonists, ifenprodil
      and Ro25-6981, also suppressed the late EPSCs. The effect of psychedelic
      hallucinogens on UP states could be partially mimicked by inhibiting glutamate
      uptake but only after blocking inhibitory group II metabotropic glutamate
      receptors. This difference suggests that hallucinogens increase glutamate
      spillover in a phasic manner unlike glutamate uptake inhibitors. Increases in
      glutamate spillover have been suggested to recruit synapses not directly in the
      pathway activated by the electrical stimulus. Such recruitment could account for
      certain cognitive, affective, and sensory perturbations generated by psychedelic
      hallucinogens.

PMID- 16292327
TI  - Role for dopamine neurons of the rostral linear nucleus and periaqueductal gray
      in the rewarding and sensitizing properties of heroin.
AB  - There is a mesencephalic dopaminergic network outside the ventral tegmental area
      (VTA), including structures such as the rostral linear nucleus (RLi) and
      periaqueductal gray (PAG). These nuclei project to neural areas implicated in
      reinforcing effects of drugs, indicating that they could participate in opiate
      reward. The objectives were to study the morphological characteristics of the
      dopamine network of the RLi/PAG region, and to discern its role on rewarding and
      sensitizing effects of heroin in rats, following dopamine depletion or local
      injection of dopaminergic antagonists. The findings indicated that this network
      is composed of small cells in the RLi/ventral PAG, large multipolar dopamine PAG
      neurons, and periaqueductal PAG neurons. Following repeated heroin, large PAG
      neurons and small RLi/ventral PAG cells (not periaqueductal neurons) were
      activated, since tyrosine-hydroxylase was adaptively induced, without changes in
      protein kinase Aalpha. After dopamine depletion, small RLi/ventral PAG neurons
      and large cells of the PAG (not periaqueductal ones) were selectively affected by
      the neurotoxin. Dopamine neurons of the nearby VTA and dorsal raphe were not
      affected, as revealed by cell counting. After lesion, 'anxiety-like' responses
      and basal locomotion were not altered. However, conditioned place preference to
      heroin was found to be abolished, as well as heroin-induced motor sensitization.
      Following infusions of dopaminergic antagonists into RLi/PAG, D(2) (not D(1))
      receptor blocking dose-dependently abolished heroin-induced reward. The present
      study provides evidence that dopamine neurons of the RLi/PAG region (excluding
      PAG periaqueductal cells) show adaptive biochemical changes after heroin, and
      mediate the rewarding and sensitizing effects of this drug. D(2) dopamine
      receptors within the RLi/PAG region participate in these effects.

PMID- 16292330
TI  - PET network abnormalities and cognitive decline in patients with mild cognitive
      impairment.
AB  - Temporoparietal and posterior cingulate metabolism deficits characterize patients
      with Alzheimer's disease (AD). A H(2)(15)O resting PET scan covariance pattern,
      derived by using multivariate techniques, was previously shown to discriminate 17
      mild AD patients from 16 healthy controls. This AD covariance pattern revealed
      hypoperfusion in bilateral inferior parietal lobule and cingulate; and left
      middle frontal, inferior frontal, precentral, and supramarginal gyri. The AD
      pattern also revealed hyperperfusion in bilateral insula, lingual gyri, and
      cuneus; left fusiform and superior occipital gyri; and right parahippocampal
      gyrus and pulvinar. In an independent sample of 23 outpatients with mild
      cognitive impairment (MCI) followed at 6-month intervals, the AD pattern score
      was evaluated as a predictor of cognitive decline. In this MCI sample, an H2(15)O
      resting PET scan was carried out at baseline. Mean duration of follow-up was 48.8
      (SD 15.5) months, during which time six of 23 MCI patients converted to AD. In
      generalized estimating equations (GEE) analyses, controlling for age, sex,
      education, and baseline neuropsychological scores, increased AD pattern score was
      associated with greater decline in each neuropsychological test score over time
      (Mini Mental State Exam, Selective Reminding Test delayed recall, Animal Naming,
      WAIS-R digit symbol; Ps<0.01-0.001). In summary, a resting PET covariance pattern
      previously reported to discriminate AD patients from control subjects was applied
      prospectively to an independent sample of MCI patients and found to predict
      cognitive decline. Independent replication in larger samples is needed before
      clinical application can be considered.

PMID- 16292329
TI  - Metabolite 1 of protopanaxadiol-type saponins, an axonal regenerative factor,
      stimulates teneurin-2 linked by PI3-kinase cascade.
AB  - We previously showed that 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (M1),
      a metabolite of protopanaxadiol-type ginseng saponins by intestinal bacteria had
      axonal extension activity in degenerated neurons, and improved memory disorder
      and synaptic loss induced by an active fragment of amyloid beta, Abeta(25-35). It
      is unknown how M1 shows these effects in neurons. To clarify the signal
      transduction mechanism of M1-induced axonal extension, phosphorylated proteins by
      M1 stimulation were identified because most cellular signal pathways are
      regulated by phosphorylation/dephosphorylation. The combination of
      immunoprecipitation and MALDI-TOF-MS revealed that teneurin-2 and mPar3 were
      specifically phosphorylated by M1 stimulation. Because mPar3 is known as an
      axonal specifying molecule and to be regulated by phosphatidylinositol 3-kinase
      (PI3-kinase), the involvement of teneurin-2 and PI3-kinase in the M1 signal was
      studied. In teneurin-2-deficient cortical neurons, M1-induced axonal extension
      and PI3-kinase activation were significantly inhibited. In addition, treatment
      with PI3-kinase inhibitor also reduced M1-induced axonal extension. These results
      suggest that M1 induces axonal outgrowth through the teneurin-2-PI3-kinase
      cascade.

PMID- 16292331
TI  - Chronic lithium chloride administration attenuates brain NMDA receptor-initiated
      signaling via arachidonic acid in unanesthetized rats.
AB  - It has been proposed that lithium is effective in bipolar disorder (BD) by
      inhibiting glutamatergic neurotransmission, particularly via N-methyl-D-aspartate
      receptors (NMDARs). To test this hypothesis and to see if the neurotransmission
      could involve the NMDAR-mediated activation of phospholipase A2 (PLA2), to
      release arachidonic acid (AA) from membrane phospholipid, we administered
      subconvulsant doses of NMDA to unanesthetized rats fed a chronic control or LiCl
      diet. We used quantitative autoradiography following the intravenous injection of
      radiolabeled AA to measure regional brain incorporation coefficients k* for AA,
      which reflect receptor-mediated activation of PLA2. In control diet rats, NMDA
      (25 and 50 mg/kg i.p.) compared with i.p. saline increased k* significantly in 49
      and 67 regions, respectively, of the 83 brain regions examined. The regions
      affected were those with reported NMDARs, including the neocortex, hippocampus,
      caudate-putamen, thalamus, substantia nigra, and nucleus accumbens. The increases
      could be blocked by pretreatment with the specific noncompetitive NMDA antagonist
      MK-801 ((5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine
      hydrogen maleate) (0.3 mg/kg i.p.), as well by a 6-week LiCl diet sufficient to
      produce plasma and brain lithium concentrations known to be effective in BD. MK
      801 alone reduced baseline values for k* in many brain regions. The results show
      that it is possible to image NMDA signaling via PLA2 activation and AA release in
      vivo, and that chronic lithium blocks this signaling, consistent with its
      suggested mechanism of action in BD.

PMID- 16292332
TI  - Correlations of androgen deficiency with clinical symptoms in Taiwanese males.
AB  - The purpose of this study was to elucidate correlations between different
      biochemical measurements of androgen deficiency and clinical symptoms in male
      residents of Taiwan. An investigation of the serum biochemical markers for
      androgen deficiency in 650 males, including total testosterone, calculated free
      testosterone, and bioavailable testosterone, was conducted. Measurements of
      clinical symptoms were obtained using a questionnaire of the androgen deficiency
      in the aging male (ADAM) by St Louis University (SLQ). Correlations among the
      biochemical markers, correlations of the biochemical markers and age, and
      relationships between the biochemical markers and the SLQ were evaluated. The
      sensitivity and specificity of the SLQ were determined. Bioavailable and
      calculated free testosterone correlated better with age than did total
      testosterone. Eighty percent of the men had a positive SLQ, and 20% had a
      negative SLQ. The percentage of positive SLQ results increased with age. No
      statistically significant difference was noted between the biochemical markers of
      bioavailable and calculated free testosterone levels and the SLQ status except
      for men aged over 70 years. The SLQ in this study showed an acceptable
      sensitivity of about 80%, but the specificity was poor (about 20%). In
      conclusion, bioavailable testosterone and calculated free testosterone were more
      closely correlated with age and may be better biochemical markers for androgen
      deficiency. SLQ might not be a suitable single measurement for androgen
      deficiency and should be used together with biochemical markers.

PMID- 16292333
TI  - Effect of sildenafil on ocular hemodynamics in 3 months regular use.
AB  - The aim of this study was to evaluate the effect of sildenafil on ocular
      hemodynamics in a group of men with erectile dysfunction in 3 months regular use.
      A total of 15 patients with erectile dysfunction were included in this
      prospective study. All patients received 50 mg doses of sildenafil (Viagra,
      Pfizer) two times per week regularly for 3 months. The following examinations
      were performed on both eyes before and after sildenafil treatment: best-corrected
      visual acuity (BCVA), intraocular pressure (IOP), color vision, anterior segment,
      and fundus examination. Using color Doppler imaging, we measured hemodynamic
      variables in the ophthalmic artery (OA), central retinal artery (CRA), and short
      posterior ciliary artery (SPCA). No significant changes in BCVA, color vision and
      IOP were found after sildenafil treatment. The anterior segment and fundus
      examinations showed no abnormalities. All Doppler parameters of OA, CRA, and SPCA
      remained nonsignificant for both eyes after sildenafil treatment. Oral sildenafil
      in 3 months regular use seems to have no effect on ocular hemodynamics.

PMID- 16292334
TI  - A video study of pain relief during newborn male circumcision.
AB  - OBJECTIVE: The purpose of this investigation was to compare the effectiveness of
      dorsal penile nerve block and topical lidocaine-prilocaine anesthesia techniques
      for pain relief during circumcision. METHODS: In total, 18 healthy term newborn
      males were divided based on anesthesia. The topical lidocaine-prilocaine group
      had six males undergoing circumcision and three males undergoing a sham
      procedure. The dorsal penile nerve block group had six males undergoing
      circumcision and three males undergoing a sham procedure. The procedures were
      videotaped and viewed by 90 noninvestigator reviewers who scored the infants'
      pain using the Neonatal Infant Pain Scale and a numeric pain scale. Statistical
      analysis utilized a P-value of <0.05 as significant. RESULTS: The median Neonatal
      Infant Pain Scale and numeric pain scores were significantly lower in the dorsal
      penile nerve block group than in the topical lidocaine-prilocaine group or the
      sham group (Neonatal Infant Pain Scale: 1.0 (range 0-6) versus 6.0 (range 2-6)
      versus 4.0 (range 0-6), P < 0.001, respectively; numeric pain scale: 2.0 (range 0
      10) versus 8.0 (range 1-10) versus 4.0 (range 0-10), P < 0.001, respectively). In
      the sham group, procedures with the dorsal penile nerve block had significantly
      lower pain scores than those with topical lidocaine-prilocaine (Neonatal Infant
      Pain Scale: 1.0 (range 0-6) versus 5.0 (range 2- 6), P < 0.001; numeric pain
      scale: 1.0 (0-8) versus 6.0 (range 0-10), P < 0.001). When reviewers were divided
      by medical background, gender or parental status, no differences in pain scores
      were observed. CONCLUSION: The dorsal penile nerve block anesthesia technique for
      newborn male circumcision was significantly more effective for pain relief than
      topical lidocaine-prilocaine.

PMID- 16292335
TI  - A study of the role of multiple site blood cultures in the evaluation of neonatal
      sepsis.
AB  - BACKGROUND: The optimal number of blood cultures needed to document sepsis in an
      ill neonate has undergone little critical evaluation. Multiple site cultures may
      improve pathogen detection if intermittent bacteremia occurs, or if a low density
      of bacteria is present in the blood. We hypothesized, however, that bacterial
      clearance is slower and bacteremia more continuous in septic neonates, so that a
      single site blood culture should be sufficient to accurately document true
      septicemia. OBJECTIVE: To determine the need for multiple site blood cultures in
      the evaluation of neonates for sepsis. DESIGN/METHODS: Clinical data were
      prospectively collected for 216 neonates who had 269 pairs of blood cultures
      taken from two different peripheral sites for the evaluation of possible sepsis.
      A minimum of 1 ml of blood was obtained from the two peripheral sites within 15
      30 min of each other. Based on prior retrospective data, we determined that 203
      infants would need to have two site blood cultures to demonstrate a significant
      improvement in pathogen detection at an alpha of 0.05 and a beta of 0.20 (80%)
      power. RESULTS: A total of 186 culture pairs were taken for evaluation of early
      onset sepsis in 186 neonates, while 83 pairs were drawn for evaluation of late
      onset sepsis in 43 neonates. In all, 21 neonates from the late-onset group were
      evaluated more than once, and 12 neonates were evaluated for both early- and late
      onset sepsis. In all, 20 (9.2%) of 216 neonates had 22 episodes of culture-proven
      sepsis at a median age of 18 days. All neonates with positive cultures had the
      same organism with a similar sensitivity pattern obtained from the two different
      peripheral sites. The other 196 study neonates had negative blood cultures from
      both sites. The single episode of early-onset sepsis was caused by Listeria
      monocytogenes, while all remaining episodes were late-onset with the following
      organisms: Staphylococcus epidermidis (7), methicillin-resistant Staphylococcus
      aureus (MRSA) (3), combined MRSA and Candida albicans (2), Candida albicans alone
      (2), late-onset Group B beta-hemolytic Streptococcus (GBS) (2), Klebsiella
      pneumoniae (2), Enterococcus fecalis (1), Escherichia coli (1), and Serratia
      marcescens (1). Since no infant grew organisms from only one of the two sites,
      the data indicate that the diagnosis of sepsis would have been made correctly in
      all infants with a single site culture. CONCLUSIONS: Two site blood cultures for
      the initial evaluation of neonatal sepsis do not have a better yield in pathogen
      detection. Sepsis in neonates can be detected with no loss of accuracy with a
      single site blood culture with blood volume of>or=1 ml.

PMID- 16292336
TI  - Communicating with parents of premature infants: who is the informant?
AB  - OBJECTIVES: To determine what sources of information are most helpful for
      neonatal intensive care unit (NICU) parents, who provides NICU parents with the
      information, and also what expectations parents have regarding obtaining
      information. STUDY DESIGN: A 19-item questionnaire was given to the parents of
      infants 32 weeks or younger prior to discharge from the NICU. RESULTS: Out of the
      101 parents who consented, almost all of the parents (96%) felt that 'the medical
      team gave them the information they needed about their baby' and that the
      'neonatologist did a good job of communicating' with them (91%). However, the
      nurse was chosen as 'the person who spent the most time explaining the baby's
      condition, 'the best source of information,' and the person who told them 'about
      important changes in their baby's condition' (P<0.01). CONCLUSION: Although the
      neonatologist's role in parent education is satisfactory, the parents identified
      the nurses as the primary source of information.

PMID- 16292337
TI  - Neurobehavioral assessment predicts differential outcome between VLBW and ELBW
      preterm infants.
AB  - OBJECTIVE: To evaluate the impact of birth weight on development of very low
      birth weight (VLBW) infants using the Neurobehavioral Assessment of the Preterm
      Infant (NAPI) before hospital discharge, and to show the relation to follow-up
      outcomes at 12, 18 and 30 months of age. STUDY DESIGN: In total, 113 preterm
      infants were assessed with the NAPI at 36 weeks postmenstrual age. Later,
      neurodevelopment was examined using the Bayley Infant Neurodevelopmental Screener
      (BINS) at 12 months and the Bayley Scales of Infant Development, at 18 and 30
      months. The cohort was divided into two groups, based on birth weight, extremely
      low birth weight (ELBW) (<1000 g) and VLBW (1000 to 1500 g). RESULTS: ELBW
      infants showed significantly lower NAPI scores compared with VLBW infants at 36
      weeks. The predischarge NAPI scores correlated with the 12, 18 and 30 months
      scores when the ELBW infants continue to have lower performance than the VLBW
      infants. In all, 14 infants developed cerebral palsy. These infants had
      significantly lower NAPI, BINS and Bayley scores compared with all other preterm
      infants. CONCLUSION: NAPI before discharge provides clinically meaningful
      information related to later neurodevelopmental outcome.

PMID- 16292338
TI  - Heat loss prevention: a systematic review of occlusive skin wrap for premature
      neonates.
AB  - OBJECTIVE: To systematically identify and synthesize investigations of the
      effectiveness of occlusive skin wrap for reducing heat loss in premature infants
      born at less than 36 weeks gestations. STUDY DESIGN: Systematic review. RESULTS:
      Three randomized controlled trials (RCT) and five historical controlled trials
      (HCT) were included. Meta-analysis shows wrapped infants had significantly higher
      admission temperatures than unwrapped infants (RCTs WMD 0.63 degrees C, 95%
      confidence interval (CI) 0.38, 0.87; HCTs WMD 0.96 degrees C, 95% CI 0.66, 1.27).
      A statistically significant difference in mortality was not found between wrapped
      and unwrapped infants in the RCTs (RR 0.72, 95% CI 0.36, 1.45) or the HCTs (RR
      0.76, 95% CI 0.51, 1.13). CONCLUSIONS: The findings suggest that occlusive skin
      wrap prevents heat loss in premature infants. The meta-analysis lacked the power
      to provide definitive results regarding the effect of wrap on mortality.

PMID- 16292339
TI  - How does neonatology fit into maternal and child health?

PMID- 16292340
TI  - Evidence for linkage to and association with type 1 diabetes at the 3q21 region
      in the Finnish population.
AB  - IDDM9-region on chromosome 3q has shown suggestive evidence for linkage to type 1
      diabetes in some but not all genome scans. We analyzed 22 microsatellite markers
      in 121 Finnish type 1 diabetes multiplex families across the IDDM9-region. Two
      point maximum LOD scores of 3.4 and 2.5 were detected with markers D3S1589 and
      D3S3606, respectively. Two markers were further tested for association using the
      transmission disequilibrium test in 384 Finnish type 1 diabetes simplex families.
      Marker AFM203wd10 showed association with type 1 diabetes (P = 0.0002 for allele
      R16). Association was present in families with children carrying the HphI-23 AA
      risk genotype at IDDM2 but not in families with children carrying protective AT
      or TT genotypes implying interaction between the two loci. Our data gives
      credence to earlier findings of linkage in this region and suggests a location
      for a polymorphism affecting type 1 diabetes susceptibility in the area
      surrounding AFM203wd10.

PMID- 16292341
TI  - Control of phosphate release from elongation factor G by ribosomal protein L7/12.
AB  - Ribosomal protein L7/12 is crucial for the function of elongation factor G (EF-G)
      on the ribosome. Here, we report the localization of a site in the C-terminal
      domain (CTD) of L7/12 that is critical for the interaction with EF-G. Single
      conserved surface amino acids were replaced in the CTD of L7/12. Whereas
      mutations in helices 5 and 6 had no effect, replacements of V66, I69, K70, and
      R73 in helix 4 increased the Michaelis constant (KM) of EF-G.GTP for the
      ribosome, suggesting an involvement of these residues in EF-G binding. The
      mutations did not appreciably affect rapid single-round GTP hydrolysis and had no
      effect on tRNA translocation on the ribosome. In contrast, the release of
      inorganic phosphate (Pi) from ribosome-bound EF-G.GDP.Pi was strongly inhibited
      and became rate-limiting for the turnover of EF-G. The control of Pi release by
      interactions between EF-G and L7/12 appears to be important for maintaining the
      conformational coupling between EF-G and the ribosome for translocation and for
      timing the dissociation of the factor from the ribosome.

PMID- 16292342
TI  - Dynamics of initiation, termination and reinitiation of DNA translocation by the
      motor protein EcoR124I.
AB  - Type I restriction enzymes use two motors to translocate DNA before carrying out
      DNA cleavage. The motor function is accomplished by amino-acid motifs typical for
      superfamily 2 helicases, although DNA unwinding is not observed. Using a
      combination of extensive single-molecule magnetic tweezers and stopped-flow bulk
      measurements, we fully characterized the (re)initiation of DNA translocation by
      EcoR124I. We found that the methyltransferase core unit of the enzyme loads the
      motor subunits onto adjacent DNA by allowing them to bind and initiate
      translocation. Termination of translocation occurs owing to dissociation of the
      motors from the core unit. Reinitiation of translocation requires binding of new
      motors from solution. The identification and quantification of further initiation
      steps--ATP binding and extrusion of an initial DNA loop--allowed us to deduce a
      complete kinetic reinitiation scheme. The dissociation/reassociation of motors
      during translocation allows dynamic control of the restriction process by the
      availability of motors. Direct evidence that this control mechanism is relevant
      in vivo is provided.

PMID- 16292343
TI  - The regulation of mDia1 by autoinhibition and its release by Rho*GTP.
AB  - Formins induce the nucleation and polymerisation of unbranched actin filaments
      via the formin-homology domains 1 and 2. Diaphanous-related formins (Drfs) are
      regulated by a RhoGTPase-binding domain situated in the amino-terminal (N
      terminal) region and a carboxy-terminal Diaphanous-autoregulatory domain (DAD),
      whose interaction stabilises an autoinhibited inactive conformation. Binding of
      active Rho releases DAD and activates the catalytic activity of mDia. Here, we
      report on the interaction of DAD with the regulatory N-terminus of mDia1
      (mDia(N)) and its release by Rho*GTP. We have defined the elements required for
      tight binding and solved the three-dimensional structure of a complex between an
      mDia(N) construct and DAD by X-ray crystallography. The core DAD region is an
      alpha-helical peptide, which binds in the most highly conserved region of mDia(N)
      using mainly hydrophobic interactions. The structure suggests a two-step
      mechanism for release of autoinhibition whereby Rho*GTP, although having a
      partially nonoverlapping binding site, displaces DAD by ionic repulsion and
      steric clashes. We show that Rho*GTP accelerates the dissociation of DAD from the
      mDia(N)*DAD complex.

PMID- 16292344
TI  - Prethymic T-cell development defined by the expression of paired immunoglobulin
      like receptors.
AB  - T cells are produced in the thymus from progenitors of extrathymic origin. As no
      specific markers are available, the developmental pathway of progenitors
      preceding thymic colonization remains unclear. Here we show that progenitors in
      murine fetal liver and blood, which are capable of giving rise to T cells, NK
      cells and dendritic cells, but not B cells, can be isolated by their surface
      expression of paired immunoglobulin-like receptors (PIR). PIR expression is
      maintained until the earliest intrathymic stage, then downregulated before the
      onset of CD25 expression. Unlike intrathymic progenitors, generation of prethymic
      PIR(+) progenitors does not require Hes1-mediated Notch signaling. These findings
      disclose a prethymic stage of T-cell development programmed for immigration of
      the thymus, which is genetically separable from intrathymic stages.

PMID- 16292345
TI  - Structure of unliganded HSV gD reveals a mechanism for receptor-mediated
      activation of virus entry.
AB  - Herpes simplex virus (HSV) entry into cells requires binding of the envelope
      glycoprotein D (gD) to one of several cell surface receptors. The 50 C-terminal
      residues of the gD ectodomain are essential for virus entry, but not for receptor
      binding. We have determined the structure of an unliganded gD molecule that
      includes these C-terminal residues. The structure reveals that the C-terminus is
      anchored near the N-terminal region and masks receptor-binding sites. Locking the
      C-terminus in the position observed in the crystals by an intramolecular
      disulfide bond abolished receptor binding and virus entry, demonstrating that
      this region of gD moves upon receptor binding. Similarly, a point mutant that
      would destabilize the C-terminus structure was nonfunctional for entry, despite
      increased affinity for receptors. We propose that a controlled displacement of
      the gD C-terminus upon receptor binding is an essential feature of HSV entry,
      ensuring the timely activation of membrane fusion.

PMID- 16292347
TI  - Dynamics of receptor/G protein coupling in living cells.
AB  - The interaction of activated G protein-coupled receptors with G proteins is a key
      event in signal transduction. Here, using a fluorescence resonance energy
      transfer (FRET)-based assay, we measure directly and in living cells the
      interaction of YFP-labeled alpha(2A)-adrenergic receptors with CFP-labeled G
      proteins. Upon agonist stimulation, a small, concentration-dependent increase in
      FRET was observed. No specific basal FRET was detected in the absence of agonist.
      Kinetics of the onset of receptor/G protein interaction were <100 ms and depended
      on expression levels of Galpha. Simultaneously recorded G protein-regulated
      inwardly rectifying K(+) channel currents revealed a maximal current response
      already at agonist concentrations producing submaximal FRET amplitudes. By
      analyzing FRET signals in the presence of a Galpha mutant, which dissociates more
      slowly from activated receptors, it was demonstrated that only a fraction of wild
      type G proteins interacts with the activated receptor at any time. Our data
      suggest that alpha(2A)-adrenergic receptors and G proteins interact by rapid
      collision coupling and indicate that there is no significant precoupling between
      these receptors and G proteins.

PMID- 16292346
TI  - A role for BARS at the fission step of COPI vesicle formation from Golgi
      membrane.
AB  - The core complex of Coat Protein I (COPI), known as coatomer, is sufficient to
      induce coated vesicular-like structures from liposomal membrane. In the context
      of biological Golgi membrane, both palmitoyl-coenzyme A (p-coA) and ARFGAP1, a
      GTPase-activating protein (GAP) for ADP-Ribosylation Factor 1, also participate
      in vesicle formation, but how their roles may be linked remains unknown.
      Moreover, whether COPI vesicle formation from Golgi membrane requires additional
      factors also remains unclear. We now show that Brefeldin-A ADP-Ribosylated
      Substrate (BARS) plays a critical role in the fission step of COPI vesicle
      formation from Golgi membrane. This role of BARS requires its interaction with
      ARFGAP1, which is in turn regulated oppositely by p-coA and nicotinamide adenine
      dinucleotide, which act as cofactors of BARS. Our findings not only identify a
      new factor needed for COPI vesicle formation from Golgi membrane but also reveal
      a surprising mechanism by which the roles of p-coA and GAP are linked in this
      process.

PMID- 16292348
TI  - Prevalence of primary hyperaldosteronism in mild to moderate hypertension without
      hypokalaemia.
AB  - Screening for primary hyperaldosteronism (PHA) is often indicated in individuals
      with resistant hypertension or hypokalaemia. However, in the far larger subset of
      the hypertensive population who do not fit into these criteria, the evidence for
      screening is conflicting and dependent on the disease prevalence. The purpose of
      this study was to examine the prevalence of PHA in a large population with mild
      to moderate hypertension and without hypokalaemia using a carefully controlled
      study protocol including a normotensive control population. Hypertensive subjects
      underwent medication washout and both hypertensive and normotensive subjects
      placed on a high-sodium diet prior to biochemical and haemodynamic testing. Study
      specific cutoff values were based on results from the normotensive population
      studied under identical conditions. A screening test (serum aldosterone/PRA ratio
      [ARR]>25 with a serum aldosterone level >8 ng/dl) was followed by a confirmatory
      test (urine aldosterone excretion rate [AER] >17 microg/24 h) to demonstrate
      evidence of PHA. An elevated ARR with a concomitant elevated serum aldosterone
      was present in 26 (7.5%) individuals. Of these, 11 (3.2%) had an elevated AER,
      consistent with evidence of PHA. Individuals with PHA had higher blood pressure
      and lower serum potassium levels while on a high-sodium diet. Sodium restriction
      neutralized these differences between PHA and essential hypertensives. The
      prevalence of PHA in this mild to moderate hypertensive population without
      hypokalaemia is at most 3.2%, a rate that might lead to excessive false positives
      with random screening in comparable populations. Hyperaldosteronism, when
      present, is responsive to sodium restriction.

PMID- 16292349
TI  - Epidemiological analysis of second primary malignancies in more than 9500
      patients treated with imatinib.

PMID- 16292351
TI  - Infectivity enhancement for adenoviral transduction of canine osteosarcoma cells.
AB  - The full realization of conditionally replicative adenoviruses (CRAds) for cancer
      therapy has been hampered by the limited knowledge of CRAd function in vivo and
      particularly in an immunocompetent host. To address this issue, we previously
      proposed a canine adenovirus type 2 (CAV2)-based CRAd for clinical evaluation in
      canine patients with osteosarcoma (OS). In this study, we evaluated infectivity
      enhancement strategies to establish the foundation for designing a potent CAV2
      CRAd with effective transduction capacity in dog osteosarcoma cells. The results
      indicate that the native CAV2 fiber-knob can mediate increased binding, and
      consequently gene transfer, in both canine osteosarcoma immortalized and primary
      cell lines relative to previously reported Ad5 infectivity-enhancement
      strategies. Gene delivery was further enhanced by incorporating a polylysine
      polypeptide onto the carboxy terminus of the CAV2 knob. This vector demonstrated
      improved gene delivery in osteosarcoma xenograft tumors. These data provide the
      rationale for generation of infectivity-enhanced syngeneic CAV2 CRAds for
      clinical evaluation in a dog osteosarcoma model.

PMID- 16292352
TI  - Intracellular trafficking of retroviral vectors: obstacles and advances.
AB  - Retroviruses are efficient vehicles for delivering transgenes in vivo. Their
      ability to integrate into the host genome, providing a permanent imprint of their
      genes in the host, is a key asset for gene therapy. Furthermore, the lentivirus
      subset of retroviruses can infect nondividing as well as dividing cells. This
      expands the cell types capable of gene therapy, driving the development of
      lentiviral vectors. However, the precise mechanisms used by different
      retroviruses to efficiently deliver their genes into cell nuclei remains largely
      unclear. Understanding these molecular mechanisms may reveal features to improve
      the efficacy of current retroviral vectors. Moreover, this knowledge may expose
      elements pliable to other gene therapy vehicles to improve their in vivo
      performance and circumvent the biosafety concerns of using retroviral vectors.
      Therefore, the mechanisms underlying the early trafficking of retroviral vectors
      in host cells are reviewed here, as understood from studying the native
      retroviruses. Events after virus entry up to nuclear delivery of the viral cDNA
      are discussed. Cellular obstacles faced by these retroviral vectors and how they
      advance beyond these barriers is emphasized.

PMID- 16292350
TI  - Herpes simplex virus 1 recombinant virions exhibiting the amino terminal fragment
      of urokinase-type plasminogen activator can enter cells via the cognate receptor.
AB  - Earlier this laboratory constructed a herpes simplex virus 1 recombinant (R5111)
      that carries a IL13 ligand inserted into glycoprotein D and can enter cells via
      the IL13Ralpha2 receptor commonly expressed on the surface of malignant glioma
      cells. In this report, we describe the properties of two recombinant viruses
      carrying chiemric gD genes. In R5181 recombinant virus the chimeric gene
      consisted on the residues 20-155 of urokinase plaminogen activator (uPA) inserted
      between residues 24 and 25 of gD. In R5182 the insert consisted of a 23-residue
      sequence encoding the uPA binding domain for the urokinase plaminogen activator
      receptor (uPAR). These viruses were constructed for three reasons, to increase
      the number of viruses that specifically target receptors on the surface of
      malignant glioma cells, to determine whether viruses exhibiting novel ligands
      could enter cells via receptors anchored to the cell surface via
      glycosylphosphatidylinositol anchor as has been recently demonstrated for
      nectin1, and to determine whether receptors other than IL13Ralpha2 could be
      targeted by genetic engineering of the virus. We report that R5181 but not R5182
      recombinant virus was able to enter cells expressing uPAR. The results indicate
      that HSV-1 recombinant viruses can be engineered to enter cells via a variety of
      unrelated nonviral receptors, including receptors that are anchored to the cells
      surface but without transmembrane domains.

PMID- 16292353
TI  - Use of artificial genomes in assessing methods for atypical gene detection.
AB  - Parametric methods for identifying laterally transferred genes exploit the
      directional mutational biases unique to each genome. Yet the development of new,
      more robust methods--as well as the evaluation and proper implementation of
      existing methods--relies on an arbitrary assessment of performance using real
      genomes, where the evolutionary histories of genes are not known. We have used
      the framework of a generalized hidden Markov model to create artificial genomes
      modeled after genuine genomes. To model a genome, "core" genes--those displaying
      patterns of mutational biases shared among large numbers of genes--are identified
      by a novel gene clustering approach based on the Akaike information criterion.
      Gene models derived from multiple "core" gene clusters are used to generate an
      artificial genome that models the properties of a genuine genome. Chimeric
      artificial genomes--representing those having experienced lateral gene transfer-
      were created by combining genes from multiple artificial genomes, and the
      performance of the parametric methods for identifying "atypical" genes was
      assessed directly. We found that a hidden Markov model that included multiple
      gene models, each trained on sets of genes representing the range of genotypic
      variability within a genome, could produce artificial genomes that mimicked the
      properties of genuine genomes. Moreover, different methods for detecting foreign
      genes performed differently--i.e., they had different sets of strengths and
      weaknesses--when identifying atypical genes within chimeric artificial genomes.

PMID- 16292354
TI  - A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas
      subtypes exist in prokaryotic genomes.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPRs) are a family
      of DNA direct repeats found in many prokaryotic genomes. Repeats of 21-37 bp
      typically show weak dyad symmetry and are separated by regularly sized,
      nonrepetitive spacer sequences. Four CRISPR-associated (Cas) protein families,
      designated Cas1 to Cas4, are strictly associated with CRISPR elements and always
      occur near a repeat cluster. Some spacers originate from mobile genetic elements
      and are thought to confer "immunity" against the elements that harbor these
      sequences. In the present study, we have systematically investigated
      uncharacterized proteins encoded in the vicinity of these CRISPRs and found many
      additional protein families that are strictly associated with CRISPR loci across
      multiple prokaryotic species. Multiple sequence alignments and hidden Markov
      models have been built for 45 Cas protein families. These models identify family
      members with high sensitivity and selectivity and classify key regulators of
      development, DevR and DevS, in Myxococcus xanthus as Cas proteins. These
      identifications show that CRISPR/cas gene regions can be quite large, with up to
      20 different, tandem-arranged cas genes next to a repeat cluster or filling the
      region between two repeat clusters. Distinctive subsets of the collection of Cas
      proteins recur in phylogenetically distant species and correlate with
      characteristic repeat periodicity. The analyses presented here support initial
      proposals of mobility of these units, along with the likelihood that loci of
      different subtypes interact with one another as well as with host cell defensive,
      replicative, and regulatory systems. It is evident from this analysis that
      CRISPR/cas loci are larger, more complex, and more heterogeneous than previously
      appreciated.

PMID- 16292355
TI  - Genome-wide association mapping in Arabidopsis identifies previously known
      flowering time and pathogen resistance genes.
AB  - There is currently tremendous interest in the possibility of using genome-wide
      association mapping to identify genes responsible for natural variation,
      particularly for human disease susceptibility. The model plant Arabidopsis
      thaliana is in many ways an ideal candidate for such studies, because it is a
      highly selfing hermaphrodite. As a result, the species largely exists as a
      collection of naturally occurring inbred lines, or accessions, which can be
      genotyped once and phenotyped repeatedly. Furthermore, linkage disequilibrium in
      such a species will be much more extensive than in a comparable outcrossing
      species. We tested the feasibility of genome-wide association mapping in A.
      thaliana by searching for associations with flowering time and pathogen
      resistance in a sample of 95 accessions for which genome-wide polymorphism data
      were available. In spite of an extremely high rate of false positives due to
      population structure, we were able to identify known major genes for all
      phenotypes tested, thus demonstrating the potential of genome-wide association
      mapping in A. thaliana and other species with similar patterns of variation. The
      rate of false positives differed strongly between traits, with more clinal traits
      showing the highest rate. However, the false positive rates were always
      substantial regardless of the trait, highlighting the necessity of an appropriate
      genomic control in association studies.

PMID- 16292358
TI  - Abstracts from the XIII International Entomophagous Insects Workshop, July 27-31,
      2003, Tucson, Arizona, USA.

PMID- 16292357
TI  - Human neutrophils kill Bacillus anthracis.
AB  - Bacillus anthracis spores cause natural infections and are used as biological
      weapons. Inhalation infection with B. anthracis, the etiological agent of
      anthrax, is almost always lethal, yet cutaneous infections usually remain
      localized and resolve spontaneously. Neutrophils are typically recruited to
      cutaneous but seldom to other forms of anthrax infections, raising the
      possibility that neutrophils kill B. anthracis. In this study we infected human
      neutrophils with either spores or vegetative bacteria of a wild-type strain, or
      strains, expressing only one of the two major virulence factors. The human
      neutrophils engulfed B. anthracis spores, which germinated intracellularly and
      were then efficiently killed. Interestingly, neutrophil killing was independent
      of reactive oxygen species production. We fractionated a human neutrophil granule
      extract by high-performance liquid chromatography and identified alpha-defensins
      as the component responsible for B. anthracis killing. These data suggest that
      the timely recruitment of neutrophils can control cutaneous infections and
      possibly other forms of B. anthracis infections, and that alpha-defensins play an
      important role in the potent anti-B. anthracis activity of neutrophils.

PMID- 16292359
TI  - Who needs an endoscopic ultrasound?

PMID- 16292356
TI  - The cell cycle independence of HIV infections is not determined by known
      karyophilic viral elements.
AB  - Human immunodeficiency virus and other lentiviruses infect cells independent of
      cell cycle progression, but gammaretroviruses, such as the murine leukemia virus
      (MLV) require passage of cells through mitosis. This property is thought to be
      important for the ability of HIV to infect resting CD4+ T cells and terminally
      differentiated macrophages. Multiple and independent redundant nuclear
      localization signals encoded by HIV have been hypothesized to facilitate
      migration of viral genomes into the nucleus. The integrase (IN) protein of HIV is
      one of the HIV elements that targets to the nucleus; however, its role in nuclear
      entry of virus genomes has been difficult to describe because mutations in IN are
      pleiotropic. To investigate the importance of the HIV IN protein for infection of
      non-dividing cells, and to investigate whether or not IN was redundant with other
      viral signals for cell cycle-independent nuclear entry, we constructed an HIV
      based chimeric virus in which the entire IN protein of HIV was replaced by that
      of MLV. This chimeric virus with a heterologous IN was infectious at a low level,
      and was able to integrate in an IN-dependent manner. Furthermore, this virus
      infected non-dividing cells as well as it infected dividing cells. Moreover, we
      used the chimeric HIV with MLV IN to further eliminate all of the other described
      nuclear localization signals from an HIV genome--matrix, IN, Viral Protein R, and
      the central polypurine tract--and show that no combination of the virally encoded
      NLS is essential for the ability of HIV to infect non-dividing cells.

PMID- 16292360
TI  - Should children with esophageal varices receive beta-blockers for the primary
      prevention of variceal hemorrhage?
AB  - Esophageal variceal hemorrhage occurs in up to 10% of children with portal
      hypertension annually, and may be fatal. In contrast to the strong evidence in
      adults that nonselective beta-adrenergic antagonism reduces the risk of variceal
      bleeding by approximately 50%, few pediatric data are available. The use of beta
      blockers for primary prophylaxis has been reported in children, but not tested in
      a randomized controlled trial. The risks and benefits in children remain
      unquantified and may differ from adults in light of the different cardiovascular
      response to hypovolemia in young children. The circumstances of the individual
      patient must, therefore, be carefully considered before beta-blockers are
      prescribed to children with esophageal varices.

PMID- 16292361
TI  - Intravenous proton pump inhibitors before endoscopy in bleeding peptic ulcer with
      high-risk stigmata: a multicentre comparative study.
AB  - BACKGROUND: It is not clear if starting intravenous proton pump inhibitors (IV
      PPI) before endoscopic therapy provides additional benefit over starting it
      afterward in patients with high-risk ulcer stigmata of peptic ulcer disease.
      METHODS: All patients who received IV pantoprazole bolus and infusion and
      underwent endoscopy in six Canadian hospitals over 20 months were reviewed. Only
      patients with high-risk ulcer stigmata (arterial bleeding, oozing, nonbleeding
      visible vessel or adherent clot) were included. Patients receiving IV PPI before
      endoscopy (before group) were compared with those who received it after endoscopy
      (after group) with respect to endoscopic findings and, secondarily, to patient
      demographics and clinical outcomes. RESULTS: The demographics and baseline
      characteristics of the before group (n=57) and the after group (n=109) were
      similar. The before group was more likely to have had IV PPI started outside of
      daytime hours, and median time to endoscopy in patients admitted with upper
      gastrointestinal bleeding was 24 h (interquartile range 9.5 to 35) in the before
      group and 11.3 h (interquartile range 3.7 to 17.2) in the after group (P<0.0001).
      At the time of endoscopy, 33% of patients in the before group had actively
      bleeding lesions (Forrest 1a or 1b) compared with 54% in the after group
      (P=0.01), but there were no significant differences in rebleeding, surgical
      rates, intensive care unit admission or death between the groups. CONCLUSION: IV
      PPI infusions before endoscopy may lower the proportion of actively bleeding
      peptic ulcer lesions at endoscopy, but this finding does not appear to affect
      rates of rebleeding, surgery or death.

PMID- 16292362
TI  - Skin metastasis from an occult esophageal adenocarcinoma.
AB  - Metastases to the skin from carcinoma arising in other organs are uncommon, yet
      they may be the first presentation of neoplastic disease. They usually originate
      from primary tumours in the breast, lung or colon. Skin metastases from
      esophageal adenocarcinoma are extremely rare. A unique case of an otherwise
      healthy patient who presented with a small, painless, mobile, clinically
      localized facial skin nodule is reported. A biopsy revealed metastatic
      adenocarcinoma, and subsequent investigations detected the primary tumour in the
      esophagus, despite no symptoms.

PMID- 16292363
TI  - Diffuse skin reaction in patient with hepatitis B, treated with two different
      formulations of pegylated interferon.
AB  - Diffuse skin reactions, commonly leading to discontinuation of the treatment,
      have been reported in patients with hepatitis C treated with interferon. They
      were not as yet described in patients treated with a newer formulation of
      interferon, namely, pegylated interferon (PegINF). A 37-year-old male patient
      with viral hepatitis B developed a diffuse urticarial skin reaction during
      treatment with two different forms of PegINF. Despite the skin reaction, the
      treatment was continued, and the patient responded very well to topical steroids
      and antihistamines. The present report suggests that despite the severity of
      reaction, withdrawal of PegINF may not always be required because this particular
      skin reaction responded well to symptomatic treatment. This is important, because
      discontinuation of PegINF may decrease the chance of achieving a sustained
      virological response in patients with viral hepatitis.

PMID- 16292364
TI  - Canadian guidelines for cardiac rehabilitation and cardiovascular disease
      prevention, second edition, 2004: executive summary.
AB  - In 2004, the Canadian Association of Cardiac Rehabilitation published the second
      edition of its Canadian Guidelines for Cardiac Rehabilitation and Cardiovascular
      Disease Prevention. This set of guidelines expanded on the previous emphasis on
      risk stratification of patients with documented coronary artery disease and the
      importance of vascular protection in the prevention of recurrent cardiac events.
      Similarly, the section on special populations in cardiac rehabilitation was
      expanded, and new sections on nutrition, complementary medicine, atherosclerosis,
      program administration, outcomes assessment, continuous quality improvement,
      information technology and research opportunities were added.

PMID- 16292365
TI  - Playing with podands based on cone-shaped cavities. How can a cavity influence
      the properties of an appended metal centre?
AB  - The potential of molecules that combine the properties of a conical cavity with
      those of a covalently-linked transition-metal centre is highlighted through the
      assessment of cyclodextrin- and calixarene-derived podands ("cavitand" ligands)
      in coordination chemistry and catalysis. Metallocavitands with coordination sites
      directed towards the interior of the generic cavity provide interesting systems
      for studying host-guest complexation processes, their enhanced strength of metal
      ion binding allowing for regioselective catalysis in a confined environment, and
      stabilisation of coordination complexes of unusual forms. Where cavitands have
      exo-oriented podand arms, the intrinsic dynamics of the cavity can dramatically
      modify metal chelation behaviour and the catalytic properties of the complexes.
      Such functionalised cavities are also useful as metal-ion transporters.

PMID- 16292366
TI  - Self-organization of Mn12 single-molecule magnets into ring structures induced by
      breath-figures as templates.
AB  - Cooling evaporation of a CH2Cl2 solution of Mn12 clusters on highly oriented
      pyrolitic graphite (HOPG) initiates the formation of water droplets that act as
      templates for the formation of self-assembled molecular magnetic rings.

PMID- 16292367
TI  - Growth of porous single-crystal Cr2O3 in a 3-D mesopore system.
AB  - Single-crystal Cr2O3 with regular mesopores has been synthesized using mesoporous
      silica KIT-6 as a template and characterized by using XRD, HRTEM and nitrogen
      adsorption/desorption.

PMID- 16292368
TI  - Ferrimagnetically ordered nanosized polyoxomolybdate-based cluster spheres.
AB  - The self-assembly of molybdate building units in the presence of Fe(II) and V(IV)
      produces the first mixed-spin heterometal keplerate-type clusters displaying
      ferrimagnetic interactions.

PMID- 16292369
TI  - Coordination chemistry of the hexavacant tungstophosphate [H2P(2W12O48]12-:
      synthesis and characterization of iron(III) complexes derived from the
      unprecedented {P2W14O54} fragment.
AB  - Clusters which display the rare cubic Fe8 topology have been obtained by reaction
      of the metastable hexavacant polyoxotungstate [H2P2W12O48]12- with basic
      trinuclear metal acetates.

PMID- 16292370
TI  - Dynamic multivalent recognition of cyclodextrin vesicles.
AB  - Cyclodextrin bilayer vesicles have dynamic membranes that recognize guest
      molecules through efficient multivalent host-guest interaction reminiscent of
      multivalent binding of a ligand with receptors in a biological membrane.

PMID- 16292371
TI  - A procedure for filling calixarene nanotubes.
AB  - Alkyl nitrites readily transfer nitrosonium into calixarene-based synthetic
      nanotubes thus offering a mild, effective and precise method to fill them.

PMID- 16292372
TI  - Ionic liquids in vacuo; solution-phase X-ray photoelectron spectroscopy.
AB  - The in situ monitoring of catalysis in Room Temperature Ionic Liquids (RTILs) is
      fundamental to the understanding of catalytic processes and the role of RTILs in
      catalytic turnover; we describe how XPS can be used to give information on both
      pure RTILs and catalytically-active RTIL-based solutions.

PMID- 16292373
TI  - A metal-oxo mediated approach to the synthesis of 21,22-diepi-membrarollin.
AB  - A synthesis of 21,22-diepi-membrarollin (14) is described, which employed
      sequential metal-oxo mediated oxidative cyclisations to introduce six of the
      seven stereogenic centres.

PMID- 16292374
TI  - Regioselective C-H activation of lanthanide-bound N-heterocyclic carbenes.
AB  - The reaction of Ln(L)N''2 (Ln = Nd, Ce; L = t-BuNCH2CH2[C{NCHCHNt-Bu}], N'' =
      N(SiMe3)2) with trimethylsilyl iodide regiospecifically functionalises the
      carbene backbone at the C4-carbene ring position to afford the silylated complex
      Ln(L')N''I; Ln(L')N''2 is isolated after attempted reduction (L' = t
      BuNCH2CH2[C{NC(SiMe3)CHNt-Bu}]) which allows a comparison of the structurally
      characterised complexes Nd(L)N''2, [Nd(L')N''I]2, and Nd(L')N''2.

PMID- 16292375
TI  - A quinone-functionalized electrode in conjunction with hydrophobic magnetic
      nanoparticles acts as a "Write-Read-Erase" information storage system.
AB  - Integration of hydrophobic magnetic nanoparticles with a quinone-functionalized
      Au electrode in a water-toluene two-phase assembly yields a "Write-Read-Erase"
      information processing system.

PMID- 16292376
TI  - Self-hydroxylation of perbenzoic acids at a nonheme iron(II) center.
AB  - Treatment of mononuclear nonheme iron(II) complexes bearing two cis-labile sites
      with perbenzoic acids results in the self-hydroxylation of the aromatic ring to
      form the corresponding iron(III)-salicylate complexes through an intramolecular
      oxo-transfer process.

PMID- 16292377
TI  - Robust gels created using a self-assembly and covalent capture strategy.
AB  - The self-assembly of dendritic building blocks containing multiple terminal
      alkenes on their surfaces yields soft gel-phase materials--subsequent Grubbs'
      metathesis leads to covalent cross-linking between the alkenes and the formation
      of robust swellable gels.

PMID- 16292378
TI  - N,N'-dimethyl-2,3-dialkylpyrazinium salts as redox-switchable surfactants? Redox,
      spectral, EPR and surfactant properties.
AB  - N,N'-dimethyl-2,3-dialkylpyrazinium salts show reversible transitions between all
      redox stages and a monolayer formation at the air-water interface that suggests
      their use as redox-switchable surfactants.

PMID- 16292379
TI  - Sugar ligands in organotitanium complexes.
AB  - Using ligands derived from D-glucose, dinuclear organotitanium compounds with
      interesting structural features were synthesized.

PMID- 16292380
TI  - Merging homogeneous catalysis with biocatalysis; papain as hydrogenation
      catalyst.
AB  - Papain, modified at Cys-25 with a monodentate phosphite ligand and complexed with
      Rh(COD)2BF4, is an active catalyst in the hydrogenation of methyl 2
      acetamidoacrylate.

PMID- 16292381
TI  - Functionalized porous silicon surfaces as MALDI-MS substrates for protein
      identification studies.
AB  - Alkyl monolayer modified porous silicon functional surfaces are employed for
      selective binding of proteins from complex mixtures (through washing of the
      deposited mixture spot using appropriate buffer) and MALDI-MS is used to detect
      the components retained on the surface.

PMID- 16292383
TI  - Palladium-catalyzed, stereoselective rearrangement of a tetracyclic allyl
      cyclopropane under arylation.
AB  - The first example of a pi,sigma domino-Heck reaction under concomitant
      rearrangement of the tetracyclic allylcyclopropane endo,exo-bishomobarrelene (5)
      is reported; the stereoselective reaction proceeds via an intramolecular
      insertion of a primarily-formed carbopalladation intermediate into a strained
      cyclopropane C-C sigma-bond, giving 9.

PMID- 16292382
TI  - General method of preparation of mesoporous M/Si3N4 nano-composites via a non
      aqueous sol-gel route.
AB  - We report a general method for the preparation of transition-metal silicon
      nitride nanocomposites; for example, mesoporous Pd-Si3N4 nanocomposite materials
      with high surface area were prepared by pyrolysis of a silicon palladium imide
      chloride complex which was synthesized by reaction of silicon diimide gel with
      palladium chloride. These porous nanocomposites catalyse organic reactions.

PMID- 16292384
TI  - Rhodium nanoparticles entrapped in boehmite nanofibers: recyclable catalyst for
      arene hydrogenation under mild conditions.
AB  - A new recyclable rhodium catalyst was synthesized by a simple procedure from
      readily available reagents, which showed high activities in the hydrogenation of
      various arenes under 1 atm H2 at room temperature.

PMID- 16292385
TI  - Highly efficient [2 + 2] intramolecular cyclizations of allenynes under microwave
      irradiation: construction of fused bicyclic compounds.
AB  - A palladium [2 + 2] cycloaddition of 1,6- and 1,7-allenyne carboxylates and
      microwave-mediated [2 + 2] cycloaddition of various 1,n-allenynes were developed
      and, particularly, the microwave irradiated [2 + 2] cycloaddition of allenynes
      can provide a simple, general and eco-friendly synthetic method to fused
      bicyclo[m,2,0]alkadienes.

PMID- 16292387
TI  - Rhodium-catalysed 1,4-addition of diarylindium hydroxides to alpha,beta
      unsaturated carbonyl compounds.
AB  - Diarylindium(III) hydroxides react with alpha,beta-unsaturated carbonyl compounds
      in the presence of a rhodium catalyst to afford the 1,4-addition products in high
      yield. This reaction demonstrates the utility of diarylindium(III) hydroxide as
      an aryl source with rhodium catalysts.

PMID- 16292388
TI  - Palladium-catalysed dimerisation-distannylation of arynes: synthesis and reaction
      of 2,2'-distannylbiaryls.
AB  - Two molar amounts of arynes were found to insert into a Sn-Sn bond of a
      distannane in the presence of a sub-stoichiometric amount of a palladium
      phosphite complex, affording straightforwardly 2,2'-distannylbiaryls.

PMID- 16292386
TI  - Novel fluorogenic calix[4]arene-bis(crown-6-ether) for selective recognition of
      thallium(I).
AB  - A new fluorogenic, dansyl group-containing derivative of 1,3-alternate
      calix[4]arene-bis(crown-6-ether) provides optical recognition of Tl+ with
      selectivity over many other metal cations, including Na+, K+, Ca2+, Ag+, Hg2+ and
      Pb2+, and embodies the first example of a calixarene-based fluorescent Tl+
      chemosensor.

PMID- 16292389
TI  - Multifunctional cadmium single source precursor for the selective deposition of
      CdO or CdS by a solution route.
AB  - We report on the interesting properties of a novel single precursor, Cd(tta)2 x
      tmeda (Htta = 2-thenoyl-trifluoroacetone, tmeda = N,N,N',N'
      tetramethylethylenediamine), ideally suited for the selective and reproducible
      fabrication of pure quality films of CdS or CdO through a simple solution
      process.

PMID- 16292391
TI  - A 7.72% efficient dye sensitized solar cell based on novel necklace-like polymer
      gel electrolyte containing latent chemically cross-linked gel electrolyte
      precursors.
AB  - Novel necklace-like polymer gel electrolytes containing latent chemically cross
      linked gel electrolyte precursors were prepared for quasi-solid dye sensitized
      solar cells with a highest efficiency of 7.72% and an active area of 0.25 cm2
      under AM1.5 condition at 100 mW cm(-2) irradiation.

PMID- 16292390
TI  - Solid phase synthesis of a spiro[5.5]ketal library.
AB  - A spiro[5.5]ketal library embodying the core structure of numerous biologically
      active natural products was synthesized employing a double intramolecular hetero
      Michael reaction as a key transformation.

PMID- 16292393
TI  - Synthesis, structure, and olefin polymerization with nickel(II) N-heterocyclic
      carbene enolates.
AB  - Two novel N-heterocylic carbene enolate nickel complexes have been prepared and
      shown to be active for ethylene and propylene polymerization to yield linear
      polymers.

PMID- 16292392
TI  - Structural diversity in the assembly of helicate-type nickel(II) complexes with
      enantiopure bis(beta-diketonate) ligands.
AB  - The tartaric acid derived bis(beta-diketonate) ligand L affords either 2:3 or 3:2
      ligand:metal complexes with nickel(II) ions depending on the stoichiometry of the
      components; the two complexes possess different electronic and geometric
      properties.

PMID- 16292394
TI  - Organolithium-mediated conversion of beta-functionalised aziridines into alkynyl
      amino alcohols and diamines.
AB  - The direct conversion of dihydrofuran and dihydropyrrole N
      triisopropylbenzenesulfonyl aziridines into alkynyl amino alcohols and diamines
      respectively can be achieved using 3 equiv. sec-butyllithium-PMDETA in THF; use
      of n-butyllithium and (-)-sparteine in Et2O gave an alkynyl amino alcohol in 60%
      ee.

PMID- 16292438
TI  - Obesity and periodontal disease in diabetic pregnant women.
AB  - This cross-sectional study investigated the impact of pregestational overweight
      and obesity on periodontal status of patients with gestational diabetes mellitus
      (GDM). Sixty pregnant women with gestational diabetes mellitus (GDM) were
      recruited for the study. According to the pregestational body mass index (BMI),
      patients were classified into 3 groups: normal, overweight or obese. The
      periodontal assessment parameters were the presence of gingival bleeding (GB) and
      bleeding on probing (BOP) per tooth. Clinical attachment loss (CAL) was assessed
      per tooth and classified according to following values: 1) absence of attachment
      loss; 2) between 1 and 2 mm, 3) between 3 and 5 mm; and 4) CAL > or = 6 mm. The
      means of individual percentage of teeth with GB and BOP and the means of the
      individual classified values of CAL were compared through ANOVA. Differences
      between the groups were established through post hoc Bonferroni test for multiple
      comparisons (p < 0.05). The analysis revealed significant differences between the
      normal group and the obese group considering GB (52.76% +/- 27.99% and 78.85% +/-
      27.44%, respectively) and CAL (2.21 +/- 0.41 and 2.61 +/- 0.54, respectively).
      Although an increase was found in BOP as the BMI increased (ranging from 55.65%
      to 75.31%), no statistically significant differences were found among the groups.
      Patients with GDM and pregestational obesity had significantly more gingivitis
      and periodontal attachment loss that those with normal pregestational BMI.
      Periodontal treatment should be considered in the establishment of future
      recommendations for metabolic control for this special group of patients.

PMID- 16292439
TI  - Blood cell attachment to root surfaces treated with EDTA gel.
AB  - Root debridement generates a smear layer which contains microorganisms and toxins
      that could interfere in periodontal healing. For this reason, different
      substances have been used to remove it and to expose collagen fibers at the tooth
      surface. Blood element adhesion to demineralized roots and clot stabilization by
      collagen fibers are extremely important for the success of periodontal surgery.
      The aim of this study was to evaluate the different patterns of blood element
      adsorption and adhesion to root surfaces only irrigated with distilled water and
      after application of a manipulated or an industrialized EDTA gel. Thirty samples
      were planed, equally divided into three groups and treated with distilled water
      (control), a manipulated EDTA gel or an industrialized one. Immediately after,
      samples were exposed to fresh blood and prepared for scanning electron
      microscopy. Untreated planed dentin presented the best results with blood cells
      entrapped in a thick web of fibrin. In the manipulated EDTA group, the web of
      fibrin was thick with sparse blood elements. The worst result was seen with the
      industrialized EDTA group, in which no blood elements could be seen. Statistical
      difference was obtained between control and industrialized EDTA groups. Surfaces
      only irrigated presented the most organized fibrin network and cell entrapment.

PMID- 16292440
TI  - Signs and symptoms of temporomandibular disorders in adolescents.
AB  - The aim of this study was to verify the prevalence of signs and symptoms of
      temporomandibular disorders (TMD) in adolescents and its relationship to gender.
      The sample comprised 217 subjects, aged 12 to 18. The subjective symptoms and
      clinical signs of TMD were evaluated, using, respectively, a self-report
      questionnaire and the Craniomandibular Index, which has 2 subscales; the
      Dysfunction Index and the Palpation Index. The results of muscle tenderness
      showed great variability (0.9-32.25%). In relation to the temporomandibular
      joint, tenderness of the superior, dorsal and lateral condyle regions occurred in
      10.6%, 10.6% and 7.83%, respectively, of the sample. Joint sound during opening
      was present in 19.8% of the sample and during closing in 14.7%. The most
      prevalent symptoms were joint sounds (26.72%) and headache (21.65%). There was no
      statistical difference between genders (p > 0.05), except for the tenderness of
      the lateral pterygoid muscles, which presented more prevalence in girls. In
      conclusion, clinical signs and symptoms of TMD can occur in adolescents; however,
      gender influence was not perceived.

PMID- 16292441
TI  - Study of the inflammatory process induced by injection of carrageenan or formalin
      in the rat temporomandibular joint.
AB  - The aim of this study was to evaluate the effects of the injection of two
      phlogistic agents, carrageenan and formalin, in the rat TMJ, and the inflammatory
      process induced by these substances. In this study, a total of 45 adult rats were
      distributed in two experimental groups and a control group. The animals were
      sacrificed after three hours, 24 hours, three days, seven days, and 15 days after
      a single injection of each substance. Histological data initially demonstrated an
      inflammatory process represented by acute infiltration, which later became mixed,
      and finally chronic in both experimental groups. Hyperplasia of the synovial
      membrane was observed after three days, being intense at seven days, and present
      after 15 days only in the formalin group. Local saline injection in the control
      group caused no inflammatory reaction. It was concluded that a single local
      injection of carrageenan or formalin was enough to induce inflammatory reaction
      in the TMJ and periarticular soft tissues, and that the resulting processes were
      similar, but more persistent in the formalin group.

PMID- 16292442
TI  - Characterization of titanium surfaces for dental implants with inorganic
      contaminant.
AB  - The aim of this research was to characterize titanium surfaces blasted with
      aluminum oxide (Al2O3) particles using the KS 400 digital image processing
      program. Samples of grade II titanium plates were submitted to blasting processes
      using particles of Al2O3, and treated with a hydrofluoric acid-based solution.
      Three digital images from each sample surface were obtained using Scanning
      Electron Microscopy, and half-quantitative chemical analyses were subsequently
      performed using Electron Dispersive Spectroscopy (EDS). In addition, parameters
      related to the alumina phase, such as the concentration level, the area and
      perimeter of the particles and their circular form factor were measured using KS
      400. The mechanical/chemical treatment caused depressions up to 10 microm on
      homogeneous surfaces. Although the chemical attack significantly removed the
      alumina phase, residual particles could still be identified by the EDS. The
      average area occupied by the alumina phase on the samples surfaces was 469.32 (+/
      284.98) microm2, the particle average perimeter was 81.61 (+/- 27.68) microm,
      and the mean circular form factor was 0.60 (+/- 0.05). Characterizing the
      titanium surface is essential in the evaluation of the material manufacturing
      process because the presence of residual aluminum particles may have deleterious
      effects on the formation of the osseous/implant tissue.

PMID- 16292443
TI  - Effects of long-term cyclosporin therapy on gingiva of rats--analysis by
      stereological and biochemical estimation.
AB  - Cyclosporin A (CsA) is used as an immunosuppressive agent and its prominent side
      effect is the induction of gingival overgrowth, which remains a significant
      problem. The risk factors appraised include the duration of treatment. However,
      there are no stereological and biochemical studies exploring the effects of long
      term CsA therapy on gingival tissue. The purpose of the present study was to
      investigate the level of TGF-beta1 in saliva and describe the densities of
      fibroblasts and collagen fibers in the gingival tissue of rats treated with CsA
      for long periods. Rats were treated for 60, 120, 180 and 240 days with a daily
      subcutaneous injection of 10 mg/kg of body weight of CsA. At the end of the
      experimental periods, saliva was collected for the determination of TGF-beta1
      levels. After histological processing, the oral epithelium and the connective
      tissue area were measured as well as the volume densities of fibroblasts (Vf) and
      collagen fibers (Vcf). After 60 and 120 days of CsA treatment, there was a
      significant increase in Vf and Vcf as well as a significant increase in TGF-beta1
      levels. After 180 and 240 days, reduction in the gingival overgrowth associated
      with significant decreases in the level of TGF-beta1, and also decreased Vf and
      Vcf, were observed. The data presented here suggest that after long-term therapy,
      a decrease in TGF-beta1 levels occurs, which might contribute to an increase in
      the proteolytic activity of fibroblasts in the gingiva, favoring the normality of
      extracellular matrix synthesis.

PMID- 16292444
TI  - Effect of different dye solutions on the evaluation of the sealing ability of
      Mineral Trioxide Aggregate.
AB  - Alkaline materials have shown incompatibility with methylene blue dye in leakage
      experiments. The goal of the present study was to analyze the effect of different
      dyes on the evaluation of the apical sealing ability of Mineral Trioxide
      Aggregate root-end fillings. Fifty-six extracted human canines were submitted to
      root canal instrumentation and obturation. After apical resection, retrograde
      cavities were prepared and teeth were randomly divided into four experimental (n
      = 13) and two control groups (n = 2). The following root-end filling materials
      were used: groups 1 and 2--Pro Root MTA (Dentsply), groups 3 and 4--zinc oxide
      eugenol cement (ZOE). Teeth in groups 1 and 3 were immersed in 2% methylene blue
      solution, while teeth in groups 2 and 4 were immersed in 0.2% rhodamine B in a
      reduced pressure environment for 48 hours. Teeth were then longitudinally
      sectioned and leakage was evaluated. Results were submitted to statistical
      analysis (ANOVA and Tukey's test). Group 1 presented the least leakage (p <
      0.05). It was concluded that the evaluation of the sealing ability of MTA is
      influenced by the dye used, since this material presented better sealing ability
      when evaluated with Methylene Blue, but was similar to ZOE when evaluated with
      rhodamine B.

PMID- 16292445
TI  - Influence of composite restorative materials and light-curing units on
      diametrical tensile strength.
AB  - The aim of this study was to evaluate the diametrical tensile strength (DTS) of
      three light-curing photo-activated composites with two different light curing
      units (LCU). Three types of dental restorative composites were used in this
      study: micro filled A110 (3M Espe); P60 (3M Espe) for posterior restorations, and
      micro-hybrid Charisma (Heraeus-Kulzer). The two LCUs were: halogen light (HAL)
      (Degulux, Degussa) and blue light emitting diode (LED) (Ultrablue, DMC). Resin
      composite specimens were inserted incrementally into a Teflon split mold
      measuring 3 mm in depth and 6 mm in internal diameter, and cured using either LCU
      (n = 10). Specimens were placed into a dark bottle containing distilled water at
      37 degrees C for 7 days. DTS tests were performed in a Universal Testing Machine
      (0.5 mm/min). Data were submitted to two-way ANOVA and Tukey's test. Results were
      (MPa): A110/HAL: 276.50 +/- 62.94a; A110/LED: 306.01 +/- 65.16a; P60/HAL: 568.29
      +/- 60.77b and P60/LED: 543.01 +/- 83.65b; Charisma/HAL: 430.94 +/- 67.28c;
      Charisma/LED: 435.52 +/- 105.12c. Results suggested that no significant
      difference in DTS was obtained with LCUs for the same composite. However, resin
      composite restorative materials presented different DTS.

PMID- 16292447
TI  - In vitro activity of zinc oxide-eugenol and glass ionomer cements on Candida
      albicans.
AB  - The aim of this study was to evaluate in vitro the antimicrobial activity of
      glass ionomer (GIC) and zinc oxide-eugenol (ZOE) cements against Candida
      albicans. Standardized GIC and ZOE specimens were maintained in contact with C.
      albicans suspension (1 x 10(6) cells/ml) at 37 degrees C for 24 h, 48 h or 7
      days. A control group without any testing cement was included. After the
      incubation period, aliquots of 0.1 ml were plated on Sabouraud's agar, and then
      the number of colonies was counted. The results were expressed as values of
      logarithms of colony-forming units per milliliter (log CFU/mL) and were analyzed
      statistically by Kruskal-Wallis ANOVA. After 48 h of incubation, the ZOE group
      presented no growth of C. albicans. GIC and control groups presented similar mean
      values at all tested periods. According to the results obtained, it could be
      concluded that, under the experimental conditions, ZOE cement was more effective
      in vitro against C. albicans than GIC.

PMID- 16292446
TI  - Effects of cleaning agents on bond strength to dentin.
AB  - The cleaning of cavity walls aims to improve adhesive restorative procedures and
      longevity of restorations. This study has compared the effect of three cleaning
      agents--sodium bicarbonate jet (Profi II, Dabi Atlante, Sao Paulo, Brazil);
      pumice paste plus a biologic detergent (Tergestesim, Probem, Sao Paulo, Brazil);
      air water spray--on the bond strength between dentin and two different adhesive
      systems: Clearfil SE Bond (Kuraray, Kioto, Japan) and Scotchbond Multi-Purpose
      Plus (3M-ESPE, Sao Paulo, Brazil). Six groups (n: 10) of dental fragments
      obtained from young adult extracted teeth were prepared, and each one received
      one of the listed surface cleaning techniques. After the adhesive application, a
      cone-shaped test body was built with AP-X (Kuraray, Kioto, Japan) or Z100 (3M
      ESPE, Sao Paulo, Brazil) composite resins, using a Teflon matrix. The specimens
      were tested for tensile bond strength after one-week storage in distilled water
      at 37 degrees C. Two pairs of fractured specimens of each group were randomly
      chosen and processed for scanning electron microscopy (SEM) analysis. ANOVA test
      of the bond strength values showed no statistical differences among the cleaning
      agents and neither between their interactions with the bonding systems. Upon SEM
      analysis, most surfaces showed mixed fractures of adhesive and cohesive failures
      in bonding resin to dentin. Based on statistical and SEM analysis, it was
      concluded that the cleaning agents studied did not interfere with the bond
      strength of the adhesive systems used to dentin.

PMID- 16292448
TI  - The influence of mold temperature on the fit of cast crowns with commercially
      pure titanium.
AB  - Commercially pure titanium (CP Ti) has been widely applied to fabricate cast
      devices because of its favorable properties. However, the mold temperature
      recommended for the manufacture of casts has been considered relatively low,
      causing inadequate castability and poor marginal fit of cast crowns. This study
      evaluated and compared the influence of mold temperature (430 degrees C--as
      control, 550 degrees C, 670 degrees C) on the marginal discrepancies of cast CP
      Ti crowns. Eight bovine teeth were prepared on a mechanical grinding device and
      impressions were used to duplicate each tooth and produce eight master dies.
      Twenty-four crowns were fabricated using CP Ti in three different groups of mold
      temperature (n = 8): 430 degrees C (as control), 550 degrees C and 670 degrees C.
      The gap between the crown and the bovine tooth was measured at 50 X magnification
      with a traveling microscope. The marginal fit values of the cast CP Ti crowns
      were submitted to the Kruskal-Wallis test (p = 0.03). The 550 degrees C group
      (95.0 microm) showed significantly better marginal fit than the crowns of the 430
      degrees C group (203.4 microm) and 670 degrees C group (213.8 microm). Better
      marginal fit for cast CP Ti crowns was observed with the mold temperature of 550
      degrees C, differing from the 430 degrees C recommended by the manufacturer.

PMID- 16292449
TI  - Prevalence and distribution of developmental enamel defects in the primary
      dentition of pre-school children.
AB  - Developmental defects of the enamel (D.D.E.) are changes in the deciduous
      dentition that have been little studied in Brazil, although they lead to
      aesthetic problems, dental sensitivity and may be predictors of dental caries.
      The objective of this study was to estimate the prevalence and distribution of
      D.D.E. in the deciduous dentition of pre-school children in the municipality of
      Itajai, Santa Catarina, in 2003. A cross-sectional study was carried out with a
      sample of 431 children aged 3 to 5 enrolled in public day care centres. All of
      the teeth were examined and the enamel defects were assessed according to the
      Modified DDE Index (FDI, 1992). The prevalence of D.D.E. was 24.4% (CI 95% 20.3
      28.5). Diffuse opacities were the most common defects found (17.9%), followed by
      hypoplasia (11.1%) and demarcated opacities (6.1%). The most affected teeth were
      the second molars (44.4%), followed by the first molars (23.5%). Defects were
      observed more frequently in the upper arch (58.2%). Assessing enamel hypoplasia
      separately, a prevalence of 15.1% (CI 95% 11.7-18.5) was observed, with the most
      affected teeth being the canines (33.6%) and second molars (33.6%). One quarter
      of the pre-school children presented enamel defects, with diffuse opacities being
      the most prevalent ones.

PMID- 16292450
TI  - Relationship between dental fluorosis and quality of life: a population based
      study.
AB  - The aim of this study was to verify the prevalence of dental fluorosis in
      schoolchildren aged 6 to 15 and its possible association with the impacts on
      their daily activities. This study is observational, cross-sectional and
      analytical. A total of 513 schoolchildren from the city of Pinheiro Preto, SC,
      took part in this study. The children were examined by three calibrated dentists,
      after obtaining a kappa > 0.80. To assess the prevalence of fluorosis, clinical
      examinations were performed according to the methodology set forth by the 4th
      edition of the WHO. To assess the impact of fluorosis on their daily activities,
      a modified OIDP (Oral Impacts on Daily Performance) was adopted. The statistical
      analysis used was the Chi-squared test with a 5% significance level. Of the total
      number of children examined, 262 (51.1%) were of the female gender and 251
      (48.9%) were of the male gender. In regard to the prevalence of fluorosis, 94
      (18.3%) of the children presented this condition, while 419 children (81.7%)
      presented a normal condition. In regard to the severity of fluorosis, few
      children presented severe alterations. No association was found between dental
      fluorosis and gender (p = 0.646), between fluorosis and socioeconomic status (p =
      0.848) or between fluorosis and access to public water supply system (p = 0.198).
      The activities that most affected children's daily performance were: oral hygiene
      (40.9%) and food intake or enjoying food (40.4%). None of the daily activities
      could be associated with the occurrence of dental fluorosis. The prevalence of
      dental fluorosis was consonant with the standards found for locations with
      optimum fluoride content in the water supply. The questionable and very slight
      levels of fluorosis were the most frequently found, without influence in the
      quality of life of the schoolchildren participating in the study.

PMID- 16292452
TI  - Imiquimod 5% cream (Aldara) in the treatment of basal cell carcinoma.
AB  - Skin cancer, the most common human cancer, is now a global epidemic. The most
      prevalent form of nonmelanoma skin cancer is basal cell carcinoma (BCC), the
      incidence of which continues to increase prompting development of new treatment
      modalities designed to add or complement current therapies. Although destructive
      modalities continue to be an important treatment options for BCC, nondestructive
      measures are a welcome addition to our therapeutic choices. Imiquimod, a topical
      immune response modifier, belongs to the family of immunostimulators. It enhances
      both the innate and acquired immune response, and has successfully treated both
      superficial and nodular basal cell carcinomas through the localized activation of
      elaborate immune response. Imiquimod can either be used alone or in combination
      with other treatment modalities. The most common adverse effects of topical use
      of imiquimod are localized to the site of application and easily managed.

PMID- 16292453
TI  - Combining chin-jowl implants with local anesthesia facial rejuvenation.
AB  - Mandibular implantation is an outpatient procedure that can be used in
      combination with other minimally invasive cosmetic interventions. Specifically,
      silastic chin implants can help create a strong chin and smooth the jaw-line in
      carefully selected patients. A standard surgical excision tray plus a few
      additional simple instruments are required, and a variety of commercially
      available implants are available for placement via an intraoral or submental
      approach. Meticulous technique minimizes the small risk of nerve injury and
      numbness. Chin-jowl implants may be preceded by neck liposuction and immediately
      followed by a face-lift to achieve overall facial enhancement.

PMID- 16292454
TI  - Ciclopirox nail lacquer 8% for the treatment of onychomycosis: a Canadian
      perspective.
AB  - Onychomycosis is prevalent in the Canadian population, and risk factors, such as
      old age and diabetes, are increasing. This condition has traditionally been
      treated using oral antifungal agents with varying degrees of success. Recently,
      ciclopirox nail lacquer 8% solution became the first topical agent approved in
      Canada for onychomycosis. Ciclopirox nail lacquer may be safe and effective for
      the treatment of onychomycosis, and certain candidates may benefit from therapy.
      Ciclopirox may be implicated for prophylactic use in order to prevent recurrent
      infection and may be used in combination with oral agents.

PMID- 16292455
TI  - Blepharoplasty: indications, outcomes, and patient counseling.
AB  - A tell-tale sign of the aging face is upper eyelid skin redundancy and lower
      eyelid bags. These changes can contribute to a "tired" appearance. Upper and
      lower blepharoplasty procedures can correct these processes. By removing skin and
      muscle, an upper eyelid blepharoplasty can give the eye a larger appearance. A
      lower blepharoplasty can remove pseudo-herniated fat, or transpose it to provide
      a smooth infraorbital contour. It appears that a transconjunctival approach for
      the lower blepharoplasty will lead to a lower incidence of eyelid malposition. An
      adjunctive procedure such as laser resurfacing may be appropriate. Patients
      should be counseled on all potential complications, including visual loss from
      muscle injury or hematoma, as well as the extent of postoperative recuperation.

PMID- 16292456
TI  - Pimecrolimus 1% cream for the treatment of atopic dermatitis.
AB  - Atopic dermatitis is a highly pruritic inflammatory disorder of the skin
      characterized by onset in infancy or childhood and a chronically relapsing
      course. Mainstay treatments are emollients and topical corticosteroids, but the
      latter are limited by side-effects from longterm use. Pimecrolimus is an
      ascomycin macrolactam derivative and a calcineurin inhibitor that targets T-cell
      activation but does not inhibit antigen-presenting cells in the skin. In multiple
      clinical trials comprising more than 19,000 patients, pimecrolimus cream has been
      shown to be very effective in suppressing atopic dermatitis and to have an
      excellent safety profile. This has also been shown in long-term studies (>2
      years) and by postmarketing experience.

PMID- 16292457
TI  - The use of lasers in the pediatric population.
AB  - Over the past 2 decades, there have been numerous advances in laser therapy of
      birth-marks in the pediatric population. Concerns regarding efficacy, overall
      benefit, and side-effects linger. We present our opinion, based upon decades of
      clinical experience, on the role of lasers to treat port wine stains, superficial
      hemangiomas, and cafe au lait macules in children.

PMID- 16292458
TI  - New developments in topical sequential therapy for psoriasis.
AB  - Topical agents for the treatment of psoriasis are indicated for patients whose
      affected area is less then 10% of their skin. However, for long-term use, their
      effectiveness can be limited. Topical sequential therapy involves the application
      of a class I corticosteroid and calcipotriene in three different phases: the
      clearance phase, the transition phase and the maintenance phase. It is an
      accepted and widely practiced technique that provides a balance between
      maximizing efficacy and minimizing side-effects thus offering patients rapid
      clearance of their psoriatic lesions and long-term maintenance of remission.

PMID- 16292459
TI  - Approaches to treatment of HIV facial lipoatrophy.
AB  - HIV-associated facial lipoatrophy has become epidemic among the greater than 1
      million HIV-infected individuals living in the United States. Those affected
      usually have well-controlled HIV disease, and are most often healthy and living
      productive lives. However, their facial appearance often suggests the opposite
      and frequently serves as a stigma and psychological burden. Treatment approaches
      may be divided into three categories: 1) Surgically placed alloplastic,
      autologous, or synthetic implants; 2) Injection of temporary fillers; 3)
      Injection of permanent fillers, including liquid injectable silicone. Salient
      aspects of each treatment are reviewed, along with new techniques and pearls on
      the correct use of liquid injectable silicone.

PMID- 16292460
TI  - [Study participation in urological specialty practices].
AB  - In the past, participation of practicing urologists in clinical trials has been
      very rare. The reasons for this have been influenced in different ways over the
      last 10 years, so that the situation has now changed. In this paper, the current
      motivation for the participation of practicing urologists in research studies is
      discussed. Moreover, we discuss the ways in which the Association of Urological
      Oncology (AUO) of the German Cancer Association promotes the participation of
      colleagues in AUO studies and how the AUO meets the needs of urologists in
      practice.

PMID- 16292461
TI  - [The study landscape for prostate cancer].
AB  - Current prostate cancer studies in Germany encompass the indications "adjuvant
      therapy", "rising PSA following radical prostatectomy", "metastasized, hormone
      sensitive prostate cancer", and "hormone refractory prostate cancer". In the
      adjuvant field, the potential of zoledronic acid for the prevention of bone
      metastases is being investigated in a large phase III trial. The activity of
      imatinib in low volume prostate cancer is being tested in patients with rising
      PSA following radical prostatectomy (phase II). The randomized phase III trial
      intermittent versus continuous hormone therapy in D1 and D2 patients has finished
      accrual and follow-up will be extended until the end of 2006. In hormone
      refractory prostate cancer(HRPC), the results of a recent phase II study
      (Association of Urological Oncology; AOU AP 33/02) were promising. This led to a
      currently activate phase III trial comparing intermittent with continuous
      chemotherapy in HRPC. The interdisciplinary study group of the AUO (Urology) and
      the ARO (Radio-oncology) has developed several new protocols which are currently
      under review by the German Cancer Aid (Deutsche Krebshilfe).

PMID- 16292463
TI  - A prospective study of depression and mortality in patients with type 2 diabetes:
      the Fremantle Diabetes Study.
AB  - AIMS/HYPOTHESIS: Depression is associated with excess mortality in patients with
      type 2 diabetes. We investigated the impact, and possible causal mechanisms, of
      depression on all-cause and cardiac mortality in patients with type 2 diabetes.
      METHODS: We recruited 1,273 patients with type 2 diabetes from a postcode-defined
      community (average age 64.1+/-11.2 years, 48.7% males, median duration of
      diabetes 4 years [range 1.0-9.0]) and followed them for 7.8+/-2.4 years.
      Depression was assessed using data obtained using a quality-of-life
      questionnaire, and cause and date of death were obtained from the state registry.
      RESULTS: Depression was present in 31.5% of subjects at recruitment. Depressed
      subjects had a longer duration of diabetes, more cardiovascular risk factors,
      CHD, cerebrovascular disease and diabetic microvascular complications at
      baseline, and higher all-cause and cardiac mortality rates during follow-up. In
      Cox proportional hazards models and after adjustment for demographic and diabetes
      related variables and cardiovascular risk factors, depression was significantly
      associated with excess all-cause and cardiac mortality. When diabetic
      microvascular and macrovascular complications were added to the Cox models,
      depression was not significantly associated with excess all-cause or cardiac
      mortality. CONCLUSIONS/INTERPRETATION: Depression in patients with type 2
      diabetes is associated with a greater prevalence of complications but is not an
      independent predictor of all-cause or cardiac mortality. Depression may
      contribute to the progression of important prognostic variables in diabetes,
      particularly macrovascular and microvascular disease.

PMID- 16292462
TI  - Primary and immortalised human pancreatic islet endothelial cells: phenotypic and
      immunological characterisation.
AB  - AIMS/HYPOTHESIS: Studies on the biology of the microvascular endothelial cells
      (MECs) that surround and penetrate the pancreatic islets are hampered by
      difficulties in isolating and culturing large numbers of pure cells. We aimed to
      morphologically and functionally characterise primary MECs purified and cultured
      from human islets, and to establish a simian virus 40 (SV40)-immortalised cell
      line from these primary cultures. MATERIALS AND METHODS: Human islet MECs were
      extracted and purified using anti-CD105 coated immunomagnetic beads, and
      endothelial markers and surface molecules analysed by flow cytometric analysis.
      An immortalised cell line was then established by using a chimeric adeno5/SV40
      virus. RESULTS: Islet MECs expressed classic and specific endothelial markers, a
      high basal level of intercellular adhesion molecule-1, and low levels of E
      selectin and TNF (previously known as TNF-alpha) inducible vascular cell adhesion
      molecule-1. IFNG (previously known as IFN-gamma) induced expression of HLA class
      II molecules. The immortalised islet MECs expanded rapidly, exhibited increased
      DNA synthesis, and were passaged approximately 30 times, without signs of
      senescence. They retained the endothelial characteristics of the parental cells,
      and behaved as the primary cells in terms of TNF stimulation of expression of
      adhesion molecules and support of leucocyte adhesion and transmigration.
      CONCLUSIONS/INTERPRETATION: The immortalised islet MECs that we have established
      could effectively represent a substitute for primary counterparts for in vitro
      studies on the role of the microvasculature in pathophysiological processes
      involved in type 1 and type 2 diabetes.

PMID- 16292464
TI  - Association of CD14 promoter polymorphisms and soluble CD14 levels in mite
      allergen sensitization of children in Taiwan.
AB  - CD14 is responsible for environmental lipopolysaccharide recognition and is a
      positional candidate gene for allergy. We hypothesized that genetic polymorphisms
      in the promoter region of the CD14 gene may be associated with Dermatophagoides
      pteronysinnus (Der p) allergen sensitization in children. Three single nucleotide
      polymorphisms (SNPs) of the CD14 promoter region, C(-159)T, A(-1,145)G, and G(
      1,359)T were genotyped, and analyzed in 240 randomized case-control school-age
      children in Taiwan. Serum concentrations of IgE and soluble CD14 (sCD14) were
      also assayed. We found a significant inverse correlation of sCD14 and total serum
      IgE levels in our study population. Moreover, sCD14 binds Der p allergen in vitro
      in a dose-dependent manner. The distribution of three SNPs genotypes was similar
      in asthmatic children and the control group. However, there was a significant
      difference in the distribution of genotype CD14 G(-1,359)T, but not C(-159)T,
      between mite-sensitive and non-sensitive children. Haplotype analysis showed
      strong linkage disequilibrium among these three SNPs in the CD14 promoter region.
      Carriers of the CD14-159C/-1,145A/-1,359T haplotype had the highest IgE and
      lowest sCD14 levels as compared to other haplotypes. Our results support the
      hypothesis that CD14 gene variants may play an important role in influencing
      allergen sensitization of children in Taiwan.

PMID- 16292466
TI  - Sex differences in clinical presentation and response in panic disorder: pooled
      data from sertraline treatment studies.
AB  - OBJECTIVE: Gender differences in clinical presentation and response to sertraline
      treatment were examined for patients diagnosed with DSM-III-R panic disorder with
      or without agoraphobia. METHOD: Data was pooled from 4 double-blind, placebo
      controlled outpatient studies (males, N = 335; females, N = 338). Two were 12
      week fixed-dose studies (sertraline 50 mg vs. 100 mg vs. 200 mg) and 2 were 10
      week flexible-dose studies (sertraline 50-200 mg). Primary outcome measures
      consisted of the Clinical Global Impression-Improvement scale (CGI-I) and change
      in panic attack frequency. RESULTS: The clinical presentation of panic disorder
      was similar except that men reported an earlier age of onset, shorter duration of
      illness, and significantly more frequent history of alcohol and/or substance
      dependence/abuse. Sertraline was significantly more effective than placebo in
      both women and men on the 2 primary outcome measures. When between-sex efficacy
      was compared, women achieved significantly greater improvement than men on panic
      frequency and CGI-I, but had equivalent improvement on all other measures. There
      was no significant between-sex difference in study completion rates, or in
      adverse event profiles. CONCLUSIONS: There was a modest but consistent trend for
      women to show superior efficacy at the end of acute sertraline treatment. This
      gender effect only occasionally achieved significance, and must be confirmed by
      future treatment research.

PMID- 16292465
TI  - The Arabidopsis leaf as a model system for investigating the role of cell cycle
      regulation in organ growth.
AB  - The role of cell cycle regulation and cell division in plant growth and organ
      development is controversial. Some experimental data are most easily interpreted
      from the 'cellular perspective' that cell division drives growth, whereas other
      observations are more consistent with the 'organismal perspective' that cell
      division is merely a consequence of growth, and to a large extent facultative.
      Here we develop a model of cell cycle regulation in the context of leaf
      development based on literature, published kinematic analysis, flow-cytometric
      and transcriptomic data obtained from growing Arabidopsis leaves. We tested this
      model by comparing the in silico inhibition of the cell cycle progression with
      the experimental observations of transgenic plants overexpressing the cell cycle
      inhibitor Arath;KRP2. The model simulates the behaviour of proliferating cells
      quite well, but is inadequate in describing the effects on expanding cells. This
      may point to a difference in the nature of the expansion process during the
      proliferating and non-dividing phase of leaf development.

PMID- 16292468
TI  - An elderly female who survived more than 30 years following a diagnosis of
      Takayasu's arteritis, complicated by fatal intestinal amyloidosis.
AB  - Compared to young patients with Takayasu's arteritis (TA), little information
      about elderly patients with TA has been reported. Additionally, no reports were
      found regarding TA cases with complications of intestinal amyloidosis. This is a
      case report of an elderly female, who developed intestinal amyloidosis, during
      late-stage TA. After years of outpatient management, she developed sudden severe
      dyspnea with pulmonary effusion, requiring hospitalization. After this event,
      betamethasone was replaced by methotrexate (MTX) for the next 34 months, but it
      seemed ineffective. After 1.5 years, she developed intractable diarrhea, followed
      by increases in BUN and serum creatinine (Cr), requiring several courses of
      hemodialysis. Colonoscopy revealed the presence of amyloid in her intestine,
      although she died of complicated sepsis caused by MRSA infection. This may be the
      first paper describing intestinal amyloidosis in a TA patient. Additionally, her
      case is rare in that she lived more than 30 years after the onset and diagnosis
      of TA.

PMID- 16292467
TI  - Psychosocial assessment by phone for high-scoring patients taking the Edinburgh
      Postnatal Depression Scale: communication pathways and strategies.
AB  - The well-documented risks associated with perinatal depression provide a strong
      argument for universal screening. However, uncertainty about what to do with
      findings is a significant barrier to implementing screenings where obstetric care
      is provided. Based on experience with a comprehensive screening program, we
      describe a protocol for those critical communication pathways that encourage a
      dynamic phone exchange between a mental health caller and the patient who has
      scored in the high range on the Edinburgh Postnatal Depression Scale. In
      addition, we present guidelines for developing an action plan for addressing
      intervention needs and closing the feedback loop to the original administrators
      of the scale.

PMID- 16292469
TI  - Raynaud's phenomenon: prevalence in an Italian population sample.
AB  - To estimate the prevalence of Raynaud's phenomenon (RP) in an Italian population
      aged 18 years and above, a validated questionnaire was mailed to a random sample
      of 3,664 subjects. Sociodemographic data and data regarding the prevalence of RP
      symptoms were collected. Trained rheumatologists carried out a subsequent
      standardized clinical examination to confirm diagnosis of RP and to detect
      associated diseases. The subjects (2,155) completed the questionnaire, with 45
      reporting RP [prevalence rate 2.1%, 95% confidence intervals (CI) 1.8-2.4]. The
      mean age [standard deviation (SD)] was 57.5 (12.7), and 40 (88.8%) were women.
      Prevalence was found higher in women (3.4%, 95% CI 2.8-4.1) than in men (0.5%,
      95% CI 0.2-0.9) (p<0.0001). A connective tissue disease was diagnosed in six
      (0.28%) subjects, three of the participants (0.14%) were identified as having RP
      associated to an idiopathic carpal tunnel syndrome, and 36 (1.67%) were diagnosed
      as having primary RP. Our study has found a lower prevalence of RP than others
      have reported. There is thought to be an association with climate and ethnic
      factors. No relationship was found regarding factors that are thought to be among
      the most relevant triggering factors for RP, e.g., occupational exposure.
      Differences with previous studies may be related to the current characteristics
      of the population surveyed.

PMID- 16292470
TI  - Behcet's disease in Lebanon: clinical profile, severity and two-decade
      comparison.
AB  - The aim of this study is to describe the clinical features of Lebanese patients
      with Behcet's disease (BD) followed up at a tertiary care center in Lebanon. A
      retrospective review of medical records of 90 patients who fulfilled the
      International Study Group (ISG) criteria for diagnosis was performed. The
      clinical characteristics and severity score were compared with those reported
      from other populations of Arab and of Turkish origin using the same diagnostic
      criteria, and a comparison over two decades for the Lebanese population was made.
      The male-to-female ratio was 2.9:1, the mean age at onset, 25.4 years, and mean
      age at diagnosis, 29.2 years. One hundred percent of the patients had mouth
      ulceration; 72.2%, genital ulceration; 59.1%, arthritis; 55.7%, papulopustular
      skin lesion; 53.9%, ocular disease; 36.8%, vascular disease; 29.5%, erythema
      nodosum; and 23.0%, neurologic disease. The characteristics of our patient
      population are similar to that reported from other countries in the region.
      However, we found a higher prevalence of vascular and neurologic disease.

PMID- 16292471
TI  - Cryofibrinogenemia associated with polyarteritis nodosa.
AB  - We report the case of a 77-year-old woman with biopsy-confirmed polyarteritis
      nodosa (PAN) associated with cryofibrinogenemia presenting with polyarthralgia
      and digital gangrene induced by cold exposure. The clinical manifestations and
      parameters measured by laboratory markers including cryofibrinogen responded well
      to corticosteroid therapy. To our knowledge, the case of the combination of PAN
      and cryofibrinogenemia has not been reported. Our case indicates that
      cryofibrinogenemia might be associated with PAN. The PAN patients with cold
      induced symptoms should be screened for cryofibrinogen.

PMID- 16292472
TI  - Detection of submicron-sized raft-like domains in membranes by small-angle
      neutron scattering.
AB  - Using coarse grained models of heterogeneous vesicles we demonstrate the
      potential for small-angle neutron scattering (SANS) to detect and distinguish
      between two different categories of lateral segregation: 1) unilamellar vesicles
      (ULV) containing a single domain and 2) the formation of several small domains or
      "clusters" (approximately 10 nm in radius) on a ULV. Exploiting the unique
      sensitivity of neutron scattering to differences between hydrogen and deuterium,
      we show that the liquid ordered (lo) DPPC-rich phase can be selectively labeled
      using chain deuterated dipalymitoyl phosphatidylcholine (dDPPC), which greatly
      facilitates the use of SANS to detect membrane domains. SANS experiments are then
      performed in order to detect and characterize, on nanometer length scales,
      lateral heterogeneities, or so-called "rafts", in approximately 30 nm radius low
      polydispersity ULV made up of ternary mixtures of phospholipids and cholesterol.
      For 1:1:1 DOPC:DPPC:cholesterol (DDC) ULV we find evidence for the formation of
      lateral heterogeneities on cooling below 30 degrees C. These heterogeneities do
      not appear when DOPC is replaced by SOPC. Fits to the experimental data using
      coarse grained models show that, at room temperature, DDC ULV each exhibit
      approximately 30 domains with average radii of approximately 10 nm.

PMID- 16292473
TI  - Confined crystallization in phase-separated poly(ethylene
      terephthalate)/poly(ethylene naphthalene 2,6-dicarboxilate) blends.
AB  - The isothermal cold crystallization of poly(ethylene terephthalate)(PET) in
      cryogenic mechanical alloyed blends of PET and Poly(ethylene naphthalene 2,6
      dicarboxilate)(PEN) 1:1 by weight has been investigated by simultaneous small and
      wide angle X-ray scattering (SAXS and WAXS) and dielectric spectroscopy (DS). For
      transesterification levels higher than 23% the blends tend to transform into a
      one-phase system and the crystallization of PET is strongly inhibited due to the
      significant reduction of the PET segment length. For lower levels of
      transesterification the blends are phase separated and the overall
      crystallization behaviour can be explained considering the confined nature of the
      PET domains in these blends. The formation of a rigid amorphous phase in the
      intra-lamellar stack amorphous regions is reduced in the blends due to a lower
      probability of stack formation in the confined PET-rich domains. The more
      effective filling of the space by the lamellar crystals in the blends provokes a
      stronger restriction to the amorphous phase mobility of PET in the blends than in
      pure PET.

PMID- 16292474
TI  - Wetting-driven structure ordering of a copolymer/homopolymer/nanoparticle mixture
      in the presence of a modulated potential.
AB  - We investigate pattern formation on a solid substrate of a diblock copolymer
      homopolymer mixture containing doping wettable nanoparticles with a preferential
      attraction for one component of the copolymers, using a three-order-parameter
      model. The presence of doping nanoparticles under the surface-interaction
      modulation breaks the isotropy in the process of microphase-separation and
      macrophase-separation. This leads to the formation of orientational microphase
      and macrophase structures due to the interplay between the phase separation and
      wetting particle ordering under a modulated potential at the late stage.
      Simulations suggest that the microphase morphology and macrophase morphology can
      be changed through adjustment of the wetting strength, the amplitude as well as
      the period of the modulated potential. It provides some important insights for
      changing microphase and macrophase structures in polymer blends by wetting-driven
      spinodal decomposition.

PMID- 16292475
TI  - Buckling of spherical shells adhering onto a rigid substrate.
AB  - Deformation of a spherical shell adhering onto a rigid substrate due to van der
      Waals attractive interaction is investigated by means of numerical minimization
      (conjugate gradient method) of the sum of the elastic and adhesion energies. The
      conformation of the deformed shell is governed by two dimensionless parameters,
      i.e., Cs/epsilon and Cb/epsilon where Cs and Cb are respectively the stretching
      and the bending constants, and epsilon is the depth of the van der Waals
      potential between the shell and substrate. Four different regimes of deformation
      are characterized as these parameters are systematically varied: (i) small
      deformation regime, (ii) disk formation regime, (iii) isotropic buckling regime,
      and (iv) anisotropic buckling regime. By measuring the various quantities of the
      deformed shells, we find that both discontinuous and continuous bucking
      transitions occur for large and small Cs/epsilon, respectively. This behavior of
      the buckling transition is analogous to van der Waals liquids or gels, and we
      have numerically determined the associated critical point. Scaling arguments are
      employed to explain the adhesion induced buckling transition, i.e., from the disk
      formation regime to the isotropic buckling regime. We show that the buckling
      transition takes place when the indentation length exceeds the effective shell
      thickness which is determined from the elastic constants. This prediction is in
      good agreement with our numerical results. Moreover, the ratio between the
      indentation length and its thickness at the transition point provides a constant
      number (2-3) independent of the shell size. This universal number is observed in
      various experimental systems ranging from nanoscale to macroscale. In particular,
      our results agree well with the recent compression experiment using
      microcapsules.

PMID- 16292476
TI  - Spectral properties of contact matrix: application to proteins.
AB  - A protein can be modelled by a set of points representing its amino acids.
      Topologically, this set of points is entirely defined by its contact matrix
      (adjacency matrix in graph theory). The contact matrix characterizing the
      relation between neighboring amino acids is deduced from Voronoi or Laguerre
      decomposition. This method allows contact matrices to be defined without any
      arbitrary cut-off that could induce arbitrary effects. Eigenvalues of these
      matrices are related with elementary excitations in proteins. We present some
      spectral properties of these matrices that reflect global properties of proteins.
      The eigenvectors indicate participation of each amino acids to the excitation
      modes of the proteins. It is interesting to compare the protein modelled as a
      close packing of amino acids, with a random close packing of spheres. The main
      features of the protein are those of a packing, a result that confirms the
      importance of the dense packing model for proteins. Nevertheless there are some
      properties, specific to the hierarchical organization of the protein: the primary
      chain order, the secondary structures and the domain structures.

PMID- 16292477
TI  - Myeloperoxidase activity imaging using (67)Ga labeled substrate.
AB  - PURPOSE: The aim of the study is to assess the feasibility of imaging specific
      activity of myeloperoxidase (MPO), a leukocyte enzyme with important roles in
      inflammation and atherosclerosis, by single photon emission computed tomography
      (SPECT) using a novel (67)Ga-labeled radiotracer obtained by conjugating
      desferrioxamine (DF) and hydroxyindolyl acetic acid in vivo. MATERIALS AND
      METHODS: A reducing substrate of MPO (I) was synthesized by reacting commercially
      available DF with 2-(5-hydroxy-1H-indol-3-yl) acetic acid in the presence of a
      coupling agent [dicyclohexyl carbodiimide (DCC)]. The chelating unit was labeled
      with (67)Ga, and its interaction with MPO was characterized using MALDI-TOF and
      UV-vis. Mice with Matrigel implants containing human MPO were used to model
      diseased tissues rich in MPO. Three hours after the injection of (67)Ga-I,
      SPECT/computed tomography (CT) imaging was performed on a high-resolution Gamma
      Medica X-SPECT system. Biodistribution studies were performed six hours after the
      injection of the radiotracer. RESULTS: The feasibility of compound I
      oligomerization in the presence of MPO and MPO-mediated cross-linking with
      proteins was initially confirmed in vitro. In vivo, a 2.7-fold increase in target
      to-muscle ratio could be measured in MPO-containing Matrigel implants in mice.
      Biodistribution experiments demonstrated a 60% increase of radioactivity in MPO
      containing vs. control (contralateral) Matrigel implants. CONCLUSION: (67)Ga-I
      can be used to image MPO activity in a model system. The accumulation mechanism
      is based on a differential pharmacokinetics because of the size increase
      resulting from (67)Ga-I interaction with the target enzyme.

PMID- 16292478
TI  - [Radiological intervention in multiply injured patients].
AB  - The most frequent cause of mortality during the first 4 h following severe trauma
      is uncontrollable hemorrhage from large arteries and parenchymal organs, whereas
      traumatic injuries of the heart and aorta are responsible for sudden death
      occurring at the accident site. It is therefore mandatory to diagnose and treat
      these injuries rapidly. Multislice spiral computed tomography is a highly useful
      imaging modality for severely injured patients. In this group of patients,
      various interventional procedures such as embolisation, stenting and temporary
      balloon occlusion may contribute to saving lives. In ruptures of the aorta and
      major arteries, stenting and temporary balloon occlusion may prevent
      exsanguination. Transcatheter embolisation is useful in hemorrhage from visceral
      organs, arteriovenous fistulas and secondary onset hemorrhage.

PMID- 16292479
TI  - [Value of radiographic examination of the knee joint for the orthopedic surgeon].
AB  - Extended radiographic examinations offer excellent options for diagnosis and
      strategy for treatment of the knee joint. The whole-leg radiograph is
      indispensable in measuring alignment for osteotomy or total knee arthroplasty
      (TKA). Fluoroscopically assisted varus-valgus stress radiographs provide the
      possibility for verifying mechanical function of the implanted knee prosthesis.
      Ultrasound examinations have been widely replaced by magnetic resonance imaging
      (MRI). MRI is the golden standard to examine intra-articular structures of the
      knee (meniscus, ligaments, cartilage) and surrounding soft tissue. For evaluating
      femoral and tibial torsion and determining axial rotation of TKA, computed
      tomography (CT) is best qualified. Imaging of the patellofemoral joint (patella
      instability) is difficult; CT scans in combination with true lateral radiographs
      seem to be helpful.

PMID- 16292480
TI  - [Urological evaluation and follow-up of the kidney transplant patient].
AB  - Patients with end-stage renal disease awaiting kidney transplantation require
      regular urological evaluation. The urologist's main task is early diagnosis and
      treatment of genitourinary malignancies and evaluation of the lower urinary
      tract. Furthermore, urologists are often confronted with the question of whether
      or not to perform pretransplant urological surgery, i.e., native nephrectomy for
      polycystic kidney disease. Urological care after kidney transplantation involves
      diagnosis and treatment of ureteral complications, malignancies, lower urinary
      tract symptoms, and last but not least erectile dysfunction, which has a
      prevalence of 20-50% among kidney transplant recipients. For the evaluation and
      follow-up of the living kidney donor, international guidelines have been
      developed in recent years to also help the urologist to perform a correct
      evaluation and follow-up of the kidney donor.

PMID- 16292481
TI  - [Urological complications after kidney transplantation].
AB  - Between August 1981 and May 2005, 1065 consecutive kidney transplants were
      performed at our center; 393 patients (36.9%) developed urological complications
      in the first 60 postoperative days. Urinary tract infections occurred in 28.5% of
      all patients. The major urological problems seen were urinary leakage and
      ureteral obstruction in 6.2% and 1.4% of the patients. Two grafts were lost due
      to severe urinary leakage. No patient death occurred due to urological
      complications. The incidence of urological complications is mainly influenced by
      the surgical procedure of organ retrieval and ureteroneocystostomy. With double-J
      stenting of the extravesical ureteroneocystostomy, we observed a significantly
      lower rate of urinary leakage but a higher rate of urinary tract infections in
      our series. Early diagnosis and treatment of urological complications may prevent
      further morbidity of our transplant patients.

PMID- 16292482
TI  - Survivin expression in ganglioglioma.
AB  - Gangliogliomas are unusual central nervous system (CNS) neoplasms occurring
      mainly in children and young adults and inducing chronic pharmacoresistant
      epilepsy. These are usually well differentiated neuroepithelial tumors composed
      of neurons in association with neoplastic glial cells. Gangliogliomas present
      with favorable outcome. However, some may recur and/or progress to anaplasia and
      be associated with a dismal prognosis. Since histopathological features do not
      consistently correlate with clinical outcome, reliable prognostic factors have
      yet to be defined in gangliogliomas. Survivin is an anti-apoptotic protein whose
      expression has been found to be of prognostic significance in many human cancers,
      including gliomas. The objective of this study was to assess survivin expression
      using immunohistochemistry in 15 gangliogliomas. Ten lesions were low-grade
      neoplasms whereas 5 were high-grade tumors. Survivin expression appeared
      restricted to the neoplastic glial component and was detected in 6/15
      gangliogliomas. Two additional tumors expressed survivin upon relapse. Half
      survivin expressing lesions displayed less than 1% immunoreactive cells. Survivin
      expression in more than 5% neoplastic glial cells was detected only in malignant
      and/or recurrent gangliogliomas. Extended lifespan in survivin expressing cells
      might enhance aggressive behavior in these tumors through accumulation of
      mutations, thereby allowing progression to malignant phenotypes. Survivin
      expression may carry a negative prognostic value in gangliogliomas.

PMID- 16292485
TI  - Higher dosing of temozolomide? Regression of an anaplastic oligoastrocytoma over
      more than three years.

PMID- 16292483
TI  - Antioxidant enzymes in oligodendroglial brain tumors: association with
      proliferation, apoptotic activity and survival.
AB  - Purpose of the study was to investigate the relationship between antioxidant
      enzyme expression and clinicopathological features in oligodendroglial tumors.
      The expression of antioxidant enzymes and related proteins (AOEs), manganese
      superoxide dismutase (MnSOD), thioredoxin (Trx), thioredoxin reductase (TrxR) and
      gammaglutamylcysteine synthetase catalytic and regulatory subunits (GLCL-C and
      GLCL-R), was studied in 85 oligodendroglial tumors. The material included 71
      primary (43 grade II and 28 grade III) and 14 recurrent (6 grade II and 8 grade
      III) tumors. Fifty-seven cases were pure oligodendrogliomas and 28 were mixed
      oligoastrocytomas. Immunoreactivity for MnSOD was found in 89%, Trx in 29%, TrxR
      in 76%, GLCL-C in 70% and GLCL-R in 68% of cases. Increased Trx expression was
      associated with higher tumor grade, cell proliferation and apoptosis (P=0.006,
      P=0.001 and P=0.003, Mann-Whitney test). Pure oligodendrogliomas showed more
      intense staining than oligoastrocytomas, especially for MnSOD (P=0.002, Mann
      Whitney test). In the total series Trx was associated with poor prognosis in
      univariate survival analysis (P=0.0343, log-rank test) and furthermore in Cox
      multivariate analysis (P=0.009) along with age (P=0.002). The results suggest
      that the expression of Trx has a correlation to patient outcome and that there
      may be some association between AOEs, like MnSOD and Trx, and clinicopathological
      features of oligodendrogliomas.

PMID- 16292484
TI  - Immunocytochemical detection of 14-3-3 in primary nervous system tumors.
AB  - 14-3-3 proteins have attracted much recent interest in the etiopathogenesis of
      human cancers owing to their involvement in the prevention of apoptosis. However,
      the expression of 14-3-3 in primary nervous system tumors has not been previously
      characterized. In this paper, Immunohistochemistry using a specific anti-14-3-3
      antibody was performed on formalin-fixed, paraffin embedded archival tissue from
      124 primary human nervous system tumors and 10 normal brain tissues. In the
      normal control brains, 14-3-3 immunoreactivity was localized mainly in the
      neuronal somata and processes, and some glial cells showed only weak
      immunoreactivity. However, 14-3-3 immunoreactivity was seen in the majority of
      astrocytomas [grade I (9/11), II (16/21), III (13/17), IV (17/21)]. There was no
      difference between the positive expression rates of 14-3-3 in different grades of
      astrocytomas (P = 0.968). But the intensity and degree of 14-3-3 immunoreactivity
      in diffuse astrocytomas, anaplastic astrocytoma, and glioblastoma multiformes
      showed trends with tumor grade, with glioblastomas having the highest positivity
      (P = 0.048). The 14-3-3 immunoreactivity was also seen in the majority of other
      gliomas [oligodendroglioma (2/3), anaplastic oligodendroglioma (4/4), ependymoma
      (1/2), anaplastic ependymoma (2/2), choroid plexus papilloma (3/3), pineocytoma
      (2/2), medulloblastoma (5/8)]. All meningiomas [syncytical (3),
      fibrous/fibroblastic (4), angiomatous (4), transitional/mixed (3)] were intensely
      and diffusely positive. All schwannomas (4), neurofibromas (2), pituitary
      adenomas (6) and craniopharyngiomas(4) also showed intense positive staining.
      These results showed that 14-3-3 is expressed in the majority of the primary
      human nervous system tumors. The up-regulated expression of 14-3-3 may be a
      common mechanism for evading apoptosis in most primary human nervous system
      tumors, and targeting 14-3-3 may be a novel promising strategy for the treatment
      of these tumors, especially for malignant tumors.

PMID- 16292486
TI  - Retrospective review of MEG visual evoked hemifield responses prior to resection
      of temporo-parieto-occipital lesions.
AB  - Visual evoked cortical magnetic field (VEF) waveforms were recorded from both
      hemifields in 21 patients with temporo-parieto-occipital mass lesions to identify
      preserved visual pathways. Fifteen patients had visual symptoms pre-operatively.
      Magnetoencephalographic (MEG) VEF responses were detected, using single
      equivalent current dipole (ECD), in 17/21 patients studied. Displaced or abnormal
      responses were seen in 15 patients with disruption of pathway in one patient.
      Three of 21 patients had alterations in the surgical approach or the planned
      resection based on the MEG findings. The surgical outcome for these three
      patients suggests that the MEG study may have played a useful role in pre
      surgical planning.

PMID- 16292487
TI  - Nasopharynx carcinoma complicated with pneumocephalus.

PMID- 16292488
TI  - Phase II trial of temozolomide in children with recurrent high-grade glioma.
AB  - PURPOSE: The objective of the study was to evaluate the efficacy and toxicity of
      Temozolomide (TMZ) administered for 5 consecutive days in three daily dosing in
      children with recurrent or refractory high-grade glioma. PATIENTS AND METHODS:
      Twenty-four patients with a median age of 10.5 years were enrolled onto this open
      label, multicenter, phase II study. The patients were previously treated with
      surgical resection (17 of 24), radiotherapy (19 of 24) and chemotherapy (18 of
      24). Therapy was administered orally three times a day for 5 consecutive days at
      the dose of 200 mg/m(2)/dx5 for chemotherapy naive patients. In patients heavily
      pretreated with chemotherapy the starting dose was of 150 mg/m(2)/dx5. RESULTS: A
      total of 95 cycles were administered. The median progression free-survival (PFS)
      was 3 months for the entire group while disease stabilization was obtained in 7
      patients (29.1%), all with supratentorial tumors. No CR or PR was observed. TMZ
      treatment showed a limited toxicity. Thrombocytopenia was the most common
      hematological adverse effect. Our data suggest a marginal activity of TMZ in
      children with recurrent high-grade glioma.

PMID- 16292489
TI  - Radiation induced meningioma with a short latent period following high dose
      cranial irradiation - case report and literature review.
AB  - Radiation induced meningiomas (RIM) are rare late complications in patients who
      have received high dose irradiation for brain tumors. The mean latency period for
      induction of RIM in most of the series is 18.7+/-10.2 years. There are only 9
      reported cases of RIM following high dose cranial irradiation with unusually
      short latency periods of less than 5 years. Herein, we report a child diagnosed
      with RIM with an unusually short latency period of 14 months. An 11-year old male
      child underwent gross total resection of medulloblastoma. Following surgery he
      received high dose craniospinal irradiation. Postoperative computed tomography
      scan (CT scan) after 1 month did not show features of any residual tumor,
      recurrence or tumor at a new site. The child was asymptomatic for 14 months and
      then presented with complaints of headache and vomiting. CT scan head showed
      multiple solid homogenously enhancing lesions in bilateral basifrontal and right
      basitemporal region. Histopathology of the lesions turned out to be atypical
      meningioma.

PMID- 16292490
TI  - Primitive neuroectodermal tumours (PNETs) located in the spinal canal; the
      relevance of classification as central or peripheral PNET : case report of a
      primary spinal PNET occurrence with a critical literature review.
AB  - Intraspinal location of central PNET (cPNET) is very rare. We present a case,
      critically review all publications of primary intraspinal cPNET occurrence and
      discuss tendencies in clinical presentation. In several previous attempts to
      summarise, authors often confused cPNET with peripheral PNET (pPNET). cPNET and
      pPNET are different entities with different immunohistochemical profiles and
      genetic backgrounds. Clinically, they are both aggressive tumours, but exhibit
      different characteristics in their local manifestation and metastatic spread.
      Survival rates are quite similar provided that treatment is applied according to
      the established protocols. Protocols in cPNET treatment differ from those for
      pPNET as regards the order of the treatment sub-modalities, specific
      chemotherapeutic regimen and intensity, radiation dose and its extent and
      consequently, the side effects. Therefore, failure to distinguish cPNET from
      pPNET leads to clinical guidance and treatment proposals based on false
      assumptions, which might effect outcomes. Often, distinguishing between cPNET and
      pPNET is easy, because they occur in different location. In the case of
      intraspinal tumour location, however, the differentiation is crucial because both
      primary cPNET and pPNET can occur intraspinally, even though this is rare.
      Nowadays, demonstrating the expression of MIC2 glycoprotein by immunocytochemical
      staining (CD99) showing the specific EWS-FLI1 chimeric gene presence in pPNET,
      offers an easy way of making a differential diagnosis between cPNET and pPNET.

PMID- 16292492
TI  - Hemorrhage in pleomorphic xanthoastrocytomas.

PMID- 16292491
TI  - Estrogen receptor beta (ERbeta) protein expression correlates with BAG-1 and
      prognosis in brain glial tumours.
AB  - Estrogen receptor beta (ERbeta) is an important mediator of estrogen function in
      a variety of tissues. Its expression declines in breast, ovarian, prostatic and
      colon carcinomas as well as in astrocytic tumours. BAG-1 is a multifunctional
      protein with an important role in neoplasia and is possibly regulated by estrogen
      receptors. One of the direct targets of BAG-1 is HSP70. The purpose of this study
      was to analyse the expression pattern of these proteins in two distinct types of
      glial neoplasms, to investigate their possible correlation and probe their impact
      on prognosis. ERbeta, BAG-1 and HSP70 protein expression was monitored
      immunohistochemically in 66 cases of astrocytomas and 20 oligodendrogliomas. In
      astrocytic tumours low ERbeta expression correlated significantly with high grade
      (P < 0.001), higher expression of cytoplasmic BAG-1 (P < 0.001) and worse
      survival (log rank P = 0.02). Multivariate analysis revealed that ERbeta
      expression had a prognostic value for overall survival in these patients (Cox P =
      0.03), which was not dependent on grade. There was also statistically significant
      association of BAG-1 nuclear expression with HSP70 cytoplasmic expression. Our
      results strengthen the hypothesis that ERbeta, BAG-1 and HSP70 play an important
      role in the pathogenesis and progression of glial neoplasms. Moreover, ERbeta
      expression in astrocytic tumors might be an important prognostic factor for
      survival.

PMID- 16292494
TI  - Tenascin-C protein is induced by transforming growth factor-beta1 but does not
      correlate with time to tumor progression in high-grade gliomas.
AB  - BACKGROUND: Tenascin-C is an extracellular matrix protein known to correlate with
      prognosis in patients with glioblastoma, probably by stimulation of invasion and
      neoangiogenesis. Transforming Growth Factor-beta1 (TGF-beta1) plays an important
      role in the biology of high-grade gliomas, partly by regulating invasion of these
      tumors into parenchyma. This study was designed to evaluate if TGF-beta1 induces
      the expression and deposition of Tenascin-C in the extracellular matrix of high
      grade gliomas which may be pivotal for the invasion of these tumors into healthy
      parenchyma. METHODS: A series of 20 high-grade gliomas was stained
      immunohistochemically with Tenascin-C- and TGF-beta1- specific antibodies.
      Expression levels of both proteins were evaluated and correlated with each other,
      time to progression and molecular and morphological markers of invasion. A
      quantitative PCR assay was performed evaluating the induction of Tenascin-C mRNA
      by treatment with TGF-beta1 in vitro. RESULTS: Tenascin-C was expressed in 18 of
      19 (95%) evaluable tumors, whereas 14 of 20 tumors (70%) expressed TGF-beta1 in a
      significant percentage of cells. Treatment with TGF-beta1 did induce the
      expression of Tenascin-C at the mRNA and protein level in vitro. The expression
      of Tenascin-C and TGF-beta1 did neighter statistically correlate with each other
      nor with time to progression. CONCLUSION: In our series, Tenascin-C and TGF-beta1
      were expressed in the vast majority of high-grade gliomas. We could not detect a
      correlation of one of the proteins with time to progression. Nevertheless, we
      describe induction of Tenascin-C by TGF-beta1, possibly providing a mechanism for
      the invasion of high-grade gliomas into healthy parenchyma.

PMID- 16292495
TI  - Neglected voices: consumers with serious mental illness speak about intensive
      case management.
AB  - This study explores early alliance formation between adult consumers with
      schizophrenic-spectrum disorders and their case managers from the consumers'
      perspectives using a prospective, cohort design. While quantitative studies have
      demonstrated positive links between the alliance and some client outcomes, such
      methods cannot reveal in concrete and authentic ways what consumers want in the
      case management relationship. This study finds that consumers can provide
      tangible and insightful information about the specifics of their case management
      relationships, confirming previous findings about the desire for connection with
      others, while extending it to include the desire for connection to the social
      world through the case manager relationship.

PMID- 16292493
TI  - Novel drug delivery system using thermoreversible gelation polymer for malignant
      glioma.
AB  - Many approaches to local tumor treatment have been reported and their efficacy
      demonstrated in patients with malignant glioma. We studied thermoreversible
      gelation polymer (TGP) as a novel drug delivery system (DDS) for treating this
      type of tumor. TGP exhibits sol-gel transition i.e., is water-soluble in the sol
      phase below the chosen sol-gel transiting temperature and water-insoluble in the
      gel phase above this temperature. We conjugated doxorubicin with TGP to prepare
      doxorubicin-TGP (DXR-TGP), then studied the kinetics of doxorubicin release from
      TGP and the antitumor activity of DXR-TGP in vitro and in vivo. The diffusive
      speed of doxorubicin from TGP was 9.4x10(-7) cm(2)/s and doxorubicin was reliably
      released from TGP. DXR-TGP showed antitumor activity against the human glioma
      cell lines T98G and U87MG and in a subcutaneous tumor model in nude mice.
      Pathologically, detection of the proliferation marker Ki-67 was considerably
      lower in the DXR-TGP group than in the control group (30-40% vs. 60-70%,
      respectively). This is to the best of our knowledge the first report of TGP as a
      novel drug delivery system, and further we provide evidence that TGP exhibits
      potential for use as a novel DDS for malignant glioma.

PMID- 16292496
TI  - Overcoming the odds: access to care for immigrant children in working poor
      families in California.
AB  - OBJECTIVES: To explore the extent to which, among working poor families,
      uninsured immigrant children experience more barriers to care than uninsured
      nonimmigrants, and compare these differences to those of insured children.
      METHODS: We used data from the 2001 California Health Interview Survey, a
      randomized, population-based telephone survey conducted from November 2000
      through September 2001. Financial and nonfinancial access to health care and
      utilization of health services were examined for 3,978 nonimmigrant and 462
      immigrant children and adolescents under the age of 18 years. We compared
      differences in crude rates across four subgroups (insured immigrants, uninsured
      immigrants, insured nonimmigrants, uninsured nonimmigrants) and in adjusted
      models controlling for socioeconomic and immigration characteristics, parental
      language, health status, and other demographic factors. RESULTS: More immigrant
      than nonimmigrant children lacked health insurance at the time of the interview
      (44% vs. 17%, p < 0.0001). Among the uninsured, immigrants had higher odds of
      perceiving discrimination (11% vs. 5%, p < 0.05) and postponing emergency room
      (ER) (16% vs. 7%, p < 0.05) and dental care (40% vs. 30%, p < 0.05) after
      controlling for covariates. Among the insured, immigrants fared worse on almost
      every access and utilization outcome. Among insured immigrants, child and parent
      undocumented status and having a non-English-speaking parent contributed to
      missed physician and ER visits. CONCLUSIONS: Disparities in access and use remain
      for immigrant poor children despite public insurance eligibility expansions.
      Insurance does not guarantee equitable health care access and use for
      undocumented children. Financial and nonfinancial barriers to health care for
      immigrant children must be removed if we are to address disparities among
      minority children.

PMID- 16292497
TI  - Unfolding features of bovine testicular hyaluronidase studied by fluorescence
      spectroscopy and fourier transformed infrared spectroscopy.
AB  - Chemical unfolding of bovine testicular hyaluronidase (HAase) has been studied by
      fluorescence spectroscopy and Fourier transformed infrared spectroscopy (FTIR).
      Thermodynamic parameters were determined for unfolding HAase from changes in the
      intrinsic fluorescence emission intensity and the formations of several possible
      unfolding intermediates have been identified. This was further confirmed by
      representation of fluorescence data in terms of 'phase diagram'. The secondary
      structures of HAase have been assigned and semiquantitatively estimated from the
      FTIR. The occurrence of conformational change during chemical unfolding as judged
      by fluorescence and FTIR spectroscopy indicated that the unfolding of HAase may
      not follow the typical two-state model.

PMID- 16292498
TI  - Cerebrospinal fluid catecholamine levels in Japanese encephalitis patients with
      movement disorders.
AB  - Norepinephrine and dopamine have important role in movement disorders but their
      role in movement disorders associated with Japanese encephalitis (JE) has not
      been evaluated. Therefore, in the present study, cerebrospinal fluid (CSF)
      catecholamine levels and its metabolites in JE patients with movement disorders
      were compared with those without JE. CSF was collected by lumbar puncture and
      analyzed by HPLC-ED. Norepinephrine, dopamine and homovanillic acid
      concentrations were significantly (P<0.005) lower in JE patients compared to
      control groups. Low levels of catecholamines in JE associated movement disorders
      compared to idiopathic Parkinson's disease and other extrapyramidal symptoms may
      be due to severe structural damage to thalamus, basal ganglia and brainstem in JE
      patients as revealed by MRI findings.

PMID- 16292499
TI  - Acrylamide-induced changes in the neurofilament protein of rat cerebrum
      fractions.
AB  - Acrylamide (ACR) is known to produce central-peripheral distal axonopathy, which
      is characterized by distal swellings and secondary degeneration both in
      experimental animals and human. Ultrastructurally, excessive accumulation of
      neurofilaments (NFs) in the distal swollen axon is a major pathological hallmark.
      However, the mechanisms of ACR axonopathy remain unknown. Twenty seven male
      Wistar rats were randomly divided into three groups. Lower and higher ACR groups
      were received 20 and 40 mg/kg ACR by i.p. injection respectively. The control
      group received physiological saline. All rats were sacrificed after 8 weeks of
      treatment and their cerebrums were dissected, homogenized and used for the
      determination of the NF proteins. In general, the levels of light NF (NF-L) and
      medium NF (NF-M) subunits increased consistently in the supernatant, whereas they
      decreased consistently in the pellet from rats treated with ACR. Compared to that
      of the control group, the levels of NF-L increased respectively by 104% and 45%
      (P<0.01) in the supernatant and decreased by 16% and 11% (P<0.01) in the pellet
      of rat cerebrums in lower and higher groups. The enhancement of NF-M was 76% and
      147% (P<0.05, P<0.01) in supernatant, and the reduction was 26% and 36% (P<0.01)
      in pellet in lower and higher group respectively. The heavy NF (NF-H) level
      changed slightly. The present results suggested that the change of NF-L and NF-M
      levels in cerebrum might be relevant to the mechanisms of the neurofilamentous
      axonopathies induced by ACR.

PMID- 16292500
TI  - Transient K+ current is blocked by lanthanum in Drosophila neurons.
AB  - The potassium A-current (IK(A)) is important in regulating the membrane potential
      between action potentials. The whole-cell patch-clamp technique was applied to
      cultured Drosophila neurons derived from embryonic neuroblasts. IK(A) was
      measured from neurons before and after application of 0.1 mM lanthanum to the
      external saline. IK(A) was smaller in the lanthanum-containing saline (7+/-1 pA)
      than in the control saline (34+/-6 pA). Activation and inactivation of IK(A) were
      unchanged by lanthanum. These results suggest that lanthanum neurotoxicity may
      lead to increased neuronal excitability. Moreover, given this inhibition of
      IK(A), lanthanum should not be used to block calcium current in studies of K+
      currents.

PMID- 16292502
TI  - Ontogenetic changes in glial fibrillary acid protein phosphorylation, glutamate
      uptake and glutamine synthetase activity in olfactory bulb of rats.
AB  - Phosphorylation of the glial fibrillary acidic protein (GFAP) in hippocampal and
      cerebellar slices from immature rats is stimulated by glutamate. This effect
      occurs via a group II metabotropic glutamate receptor in the hippocampus and an
      NMDA ionotropic receptor in the cerebellum. We investigated the glutamate
      modulation of GFAP phosphorylation in the olfactory bulb slices of Wistar rats of
      different ages (post-natal day 15 = P15, post-natal day 21 = P21 and post-natal
      day 60 = P60). Our results showed that glutamate stimulates GFAP phosphorylation
      in young animals and this is mediated by NMDA receptors. We also observed a
      decrease in glutamate uptake at P60 compared to P15, a finding similar to that
      found in the hippocampus. The activity of glutamine synthetase was elevated after
      birth, but was found to decrease with development from P21 to P60. Together,
      these data confirm the importance of glutamatergic transmission in the olfactory
      bulb, its developmental regulation in this brain structure and extends the
      concept of glial involvement in glutamatergic neuron-glial communication.

PMID- 16292503
TI  - Functional significance of the preconditioning-induced down-regulation of
      glutamate transporter GLT-1 in neuron/astrocyte co-cultures.
AB  - In the brain, prior sublethal ischemia (preconditioning, PC) is known to produce
      tolerance of neurons to subsequent lethal ischemia. This study aims at
      elucidating what alterations were induced in neurons and/or astrocytes by PC
      treatment. The rise in the extracellular concentration of glutamate during
      ischemia was markedly suppressed by the prior PC treatment. Immunocytochemical
      and Western blot analyses demonstrated that the expression of the astrocytic
      glutamate transporter GLT-1 was transiently down-regulated after the PC insult.
      The PC insult possibly suppressed the neuron-derived factors up-regulating GLT-1.
      Here we show that PC-induced down-regulation of GLT-1 is crucial for the
      increased neuronal resistance to subsequent severe ischemic insult.

PMID- 16292501
TI  - Calpain sensitive regions in the N-terminal cytoplasmic domains of glycine
      transporters GlyT1A and GlyT1B.
AB  - Glycine transporters are members of the Na+/Cl- dependent transporter gene family
      and play crucial roles in regulating inhibitory as well as excitatory
      neurotransmission. In this report we show that calcium elevation in spinal cord
      synaptosomes decreases the levels of glycine transporter, GlyT1, N-terminal
      immunoreactivity, and that this decrease can be blocked by calpain inhibitor.
      Sequencing of GST fusion proteins containing the N-terminal domains of GlyT1A and
      B splice variants cleaved with rat recombinant calpain identified calpain
      cleavage sites after glycine 17 in GlyT1B and N-terminally of the first conserved
      arginine residue in both GlyT1A and GlyT1B. Expression in HEK293 cells revealed
      that truncation of the N-terminus of GlyT1 results in significant inhibition of
      glycine uptake. A syntaxin1A GST fusion protein was able to pull-down N
      terminally deleted GlyT1, indicating that calpain cleavage does not eliminate
      syntaxin1A binding. These results suggest that calpain cleavage may regulate the
      transport activity/turnover of GlyT1 in vivo by cleaving its N-terminal domain.

PMID- 16292504
TI  - In vivo evaluation of the effect of zonisamide on the hippocampal redox state
      during kainic acid-induced seizure status in rats.
AB  - The aim in this study is to observe the hippocampal redox state during kainic
      acid (KA)-induced seizure status, and examine the effect of systemic preinjection
      of anticonvulsant zonisamide (ZNS) on the hippocampal redox. To perform under a
      freely moving state, in vivo microdialysis method was applied to electron
      paramagnetic resonance (EPR) spectroscopy. Half-life of 3-methoxycarbonyl-2,2,5,5
      tetramethylpyrrolidine-1-oxyl (PCAM), a five-membered ring nitroxide radical, was
      used for the indicator of the hippocampal antioxidant ability. The changes in EPR
      signal intensities of PCAM decreased exponentially in all rats used. The average
      half-lives of PCAM was significantly shorter in the rats pretreated with ZNS than
      that of control group, and while the average half-lives of PCAM in the perfusate
      was significantly longer in the rats KA-induced status epilepticus than that of
      control (P < 0.01). Those of PCAM in the ZNS-pretreated rats followed by KA
      injection were almost the same as those of control. These findings indicate that
      the pretreatment of ZNS increased the antioxidant ability in the hippocampus
      during KA-induced seizure. This study is the first in vivo evaluation of the
      antioxidant ability of ZNS as neuroprotective role against the free radicals
      performed under the condition of freely moving rats during seizure status.

PMID- 16292506
TI  - Activated cyclic AMP-response element binding protein (CREB) is expressed in a
      myelin-associated protein in chick.
AB  - Cyclic AMP response element (CRE) is a specific DNA sequence, which mediates
      transcriptional activation in the response to the cyclic AMP-activated and
      protein kinase A dependent signaling pathway. In the present study,
      phosphorylated CRE binding protein (CREB) immunoreactivity was mainly localized
      in the white matter of chick central nervous system (CNS). We have further
      confirmed the specificity of phospho-CREB immunoreaction in myelin using
      demyelinated optic nerve induced by lysophophatidylcholine (LPC), which is known
      to produce demyelination with little axonal damage. Double immunofluorescent
      analyses with myelin basic protein (MBP) and transferrin binding protein (TfBP),
      oligodendrocyte marker showed that phospho-CREB recognized a myelin-related
      protein in chick. Immunoblot analyses showed that phospho-CREB recognized a
      protein with molecular weights of approximately 70 kDa. Our data suggest that the
      antigen recognized by phospho-CREB is a myelin-associated protein in the chick
      CNS.

PMID- 16292505
TI  - Glutaric acid administration impairs energy metabolism in midbrain and skeletal
      muscle of young rats.
AB  - A genetic mice model of glutaric acidemia type I (GAI) has recently been
      developed, however affected animals do not develop the striatal damage
      characteristic of patients with this disorder. Therefore, the initial aim of the
      present work was to induce high glutaric acid (GA) concentrations in rat brain
      similar to those found in GAI patients through subcutaneous injection of GA. High
      brain GA concentrations (up to 0.60 micromol/g congruent with 0.60mM) were
      achieved by a single subcutaneous injection of saline-buffered GA (5 micromol/g
      body weight) to Wistar rats of 7-22 days of life. GA brain levels were about 10
      fold lower than in plasma and 5-fold lower than in skeletal and cardiac muscles,
      indicating that the permeability of the blood brain barrier to GA is low. We also
      aimed to use this model to investigate neurochemical parameters in the animals.
      Thus, we evaluated the effect of this model on energy metabolism parameters in
      midbrain, in which the striatum is localized, as well as in peripheral tissues
      (skeletal and cardiac muscles) of 22-day-old rats. Control rats were treated with
      saline in the same volumes. We verified that CO2 production from glucose was not
      altered in midbrain of rats treated with GA, indicating a normal functioning of
      the tricarboxylic acid cycle. Creatine kinase activity was also not changed in
      midbrain, skeletal and cardiac muscles. In contrast, complex I-III activity of
      the respiratory chain was inhibited in midbrain (25%), while complexes I-III
      (25%) and II-III (15%) activities were reduced in skeletal muscle, with no
      alterations found in cardiac muscle. These data indicate that GA administration
      moderately impairs cellular energy metabolism in midbrain and skeletal muscle of
      young rats.

PMID- 16292507
TI  - Alpha-ketoisocaproic acid increases phosphorylation of intermediate filament
      proteins from rat cerebral cortex by mechanisms involving Ca2+ and cAMP.
AB  - We have previously described that alpha-ketoisocaproic acid (KIC), the main
      metabolite accumulating in maple syrup urine disease (MSUD), increased the in
      vitro phosphorylation of cytoskeletal proteins in cerebral cortex of 17- and 21
      day-old rats through NMDA glutamatergic receptors. In the present study we
      investigated the protein kinases involved in the effects of KIC on the
      phosphorylating system associated with the cytoskeletal fraction and provided an
      insight on the mechanisms involved in such effects. Results showed that 1 mM KIC
      increased the in vitro incorporation of 32P into intermediate filament (IF)
      proteins in slices of 21-day-old rats at shorter incubation times (5 min) than
      previously reported. Furthermore, this effect was prevented by 10 microM KN-93
      and 10 microM H-89, indicating that KIC treatment increased Ca2+/calmodulin-
      (PKCaMII) and cAMP- (PKA) dependent protein kinases activities, respectively.
      Nifedipine (100 microM), a blocker of voltage-dependent calcium channels (VDCC),
      DL-AP5 (100 microM), a NMDA glutamate receptor antagonist and BAPTA-AM (50
      microM), a potent intracellular Ca2+ chelator, were also able to prevent KIC
      induced increase of in vitro phosphorylation of IF proteins. In addition, KIC
      treatment was able to significantly increase the intracellular cAMP levels. This
      data support the view that KIC increased the activity of the second messenger
      dependent protein kinases PKCaMII and PKA through intracellular Ca2+ levels.
      Considering that hyperphosphorylation of cytoskeletal proteins is related to
      neurodegeneration it is presumed that the Ca2+-dependent hyperphosphorylation of
      IF proteins caused by KIC may be involved to the neuropathology of MSUD patients.

PMID- 16292508
TI  - Effects of manganese on extracellular levels of dopamine in rat striatum: an
      analysis in vivo by brain microdialysis.
AB  - The aim of this study is to determine the effects of intrastriatal administration
      of MnCl2, on the extracellular levels of dopamine (DA) and metabolites
      dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in basal
      conditions and stimulated by depolarization with KCl and pargyline
      administration. Also, we studied the effect of MnCl2 on extracellular levels of l
      Dopa in the presence of aromatic amino acid decarboxylase (AADC) inhibitor 3
      hydroxybencilhydracine-HCl (NSD 1015). This study concluded that MnCl2, reduced
      the basal and K+-stimulated DA-release in striatum, without notably affecting the
      DOPAC and HVA levels. Intraperitoneal injection of pargyline increased striatal
      DA levels, decreasing DOPAC and HVA levels. The infusion of MnCl2 removed the
      increase in DA levels, without affecting DOPAC and HVA levels. Perfusion of NSD
      1015 increased the extracellular levels of L-DOPA in striatum, and MnCl2
      increased the effect of NSD1015 on L-Dopa.

PMID- 16292509
TI  - Nociceptive response and adenine nucleotide hydrolysis in synaptosomes isolated
      from spinal cord of hypothyroid rats.
AB  - Purinergic system exerts a significant influence on the modulation of pain
      pathways at the spinal site. Adenosine has antinociceptive properties in
      experimental and clinical situations, while ATP exerts pronociceptive actions in
      different pain models. In this study we investigated the hydrolysis of ATP to
      adenosine in synaptosomes from spinal cord in parallel with the nociceptive
      response of rats at different ages after hypothyroidism induction. Hypothyroidism
      elicited a significant increase in AMP hydrolysis to adenosine in synaptosomes
      from spinal cord of rats subjected to neonatal hypothyroidism and in 420-day-old
      rats submitted to thyroidectomy. Accordingly, these rats presented an analgesic
      response as a consequence of hypothyroidism. In contrast, the ATP hydrolysis was
      decreased in the spinal cord of 60-day-old hypothyroid rats in parallel with a
      significant increase in nociceptive response. These results indicate the
      involvement of adenine nucleotides in the control of the hypothyroidism-induced
      nociceptive response during development.

PMID- 16292510
TI  - Muller Cells as a source of brain-derived neurotrophic factor in the retina:
      noradrenaline upregulates brain-derived neurotrophic factor levels in cultured
      rat Muller cells.
AB  - Muller cells, the predominant glial cells in the retina, are thought to play
      important roles in the survival of retinal neurons. Previous studies have
      demonstrated that Muller cells express brain-derived neurotrophic factor (BDNF),
      which has a pronounced neurotrophic effect on retinal ganglion cells. In this
      study, we investigated whether Muller cells express and release BDNF in culture.
      Reverse transcriptase-PCR, immunocytochemistry and Western blotting revealed that
      Muller cells produce BDNF mRNA and protein. Using the enzyme-linked immunosorbant
      assay, BDNF protein levels in Muller cells and their conditioned medium were
      quantified, demonstrating that Muller cells produce and release high levels of
      BDNF. Noradrenaline administration caused an upregulation of BDNF mRNA and
      protein expression by cultured Muller cells. These results suggest that Muller
      cells may act as an endogenous source of BDNF in the retina. Furthermore,
      induction of BDNF expression by adrenergic agonists may provide a therapeutic
      approach to retinal neurodegenerative disorders.

PMID- 16292511
TI  - Aging-related correlation of insulin-degrading enzyme with gamma-secretase
      generated products involving insulin and glucose levels in transgenic mice.
AB  - Insulin-degrading enzyme (IDE) is a 110-kDa thiol zinc-methalloendopeptidase that
      can cleave small Abeta peptides and the APP intracellular domain (AICD). The aim
      of this study was to examine aging-related correlation of IDE with gamma
      secretase-generated products involving insulin and glucose levels in transgenic
      brains expressing neuron-specific enolase (NSE)-controlled human mutant
      presenilin-2 (hPS2m). Herein, we concluded that the levels of IDE expression in
      transgenic brains were decreased relative to those of control mice at 15 months
      of age. In parallel, inhibition in the IDE expression at this age underlies to
      the levels-up of Abeta-42, AICD, gamma-secretase, and glucose with a level-down
      of insulin. Thus, IDE expression is critical target for the therapeutic trials.

PMID- 16292512
TI  - Towards unraveling ethanol-specific neuro-metabolomics based on ethanol
      responsive genes in vivo.
AB  - The search for genetic causes involved in alcohol dependence/response has been
      challenging. Understanding the mechanisms of action and interaction of the genes
      implicated in alcohol response is a key towards understanding the problem. Sixty
      nine ethanol responsive genes were used in a detailed genome-wide examination to
      study their neuro-metabolomics. These genes displayed very close interactions
      among themselves with over 400 regulation events and 100 expression events
      contributing to 15 different cell processes including cell signaling, transport
      and proliferation. Acute ethanol produces a global effect on the neuro
      metabolome. Ethanol alone was found to interact with over 1000 genes and cell
      events. The study revealed that the ethanol responsive genes directly regulate
      and are themselves regulated by the activity of other proteins and cell
      processes. We propose a pathway involving nine interacting ethanol responsive
      genes, which may determine differential ethanol effects in the brain in vivo.

PMID- 16292513
TI  - Depressant effect of mitochondrial respiratory complex inhibitors on proteasome
      inhibitor-induced mitochondrial dysfunction and cell death in PC12 cells.
AB  - The addition of rotenone (inhibitor of respiratory complex I), 3-nitropropionic
      acid (complex II inhibitor), harmine (inhibitor of complexes I and II) and
      cyclosporin A (CsA, an inhibitor of the mitochondrial permeability transition)
      reduced the nuclear damage, loss in the mitochondrial transmembrane potential,
      cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the
      formation of reactive oxygen species and depletion of GSH in differentiated PC12
      cells treated with MG132, a proteasome inhibitor. Meanwhile, rotenone, 3
      nitropropionic acid and harmine did not affect the inhibitory effect of CsA or
      trifluoperazine (an inhibitor of the mitochondrial permeability transition and
      calmodulin antagonist) on the cytotoxicity of MG132. The results suggest that
      proteasome inhibition-induced mitochondrial dysfunction and cell injury may be
      attenuated by the inhibitions of respiratory chain complex I and II. The
      cytoprotective effect of the mitochondrial permeability transition prevention not
      appears to be modulated by respiratory complex inhibition.

PMID- 16292514
TI  - Active immunisation against nicotine blocks the reward facilitating effects of
      nicotine and partially prevents nicotine withdrawal in the rat as measured by
      dopamine output in the nucleus accumbens, brain reward thresholds and somatic
      signs.
AB  - We recently showed that active immunisation with the nicotine immunoconjugate
      IP18-KLH reduces the nicotine-induced increase in dopamine (DA) output in the
      nucleus accumbens (NAC) and prevents reinstatement of nicotine-seeking behaviour
      in rats. These effects are mediated by altered distribution of nicotine,
      resulting in reduced amounts of nicotine reaching the brain, thereby interfering
      with the rewarding properties of the drug. The present study was designed to
      explore the effect of immunisation against nicotine on mecamylamine-precipitated
      nicotine withdrawal as assessed by the reduction in DA output in the NAC in rats.
      Measuring brain reward thresholds and somatic signs of nicotine withdrawal, the
      effects of immunisation were also tested during chronic nicotine treatment and
      after its withdrawal. Finally, we examined the effect of immunisation on
      challenge injections of nicotine on brain reward thresholds after the increases
      in somatic signs and reward thresholds associated with nicotine withdrawal had
      dissipated. The results show that immunisation with IP18-KLH prevented the
      decrease in DA output in the NAC associated with mecamylamine-precipitated
      nicotine withdrawal. Moreover, immunisation against nicotine did not precipitate
      a withdrawal syndrome, as measured by brain reward thresholds and somatic signs,
      in rats chronically exposed to nicotine. Furthermore, the withdrawal syndrome
      elicited after cessation of chronic nicotine administration was attenuated in
      immunised rats compared to that of mock-immunised rats. Finally, the lowering in
      reward thresholds after nicotine challenge injections was attenuated in both
      naive and previously nicotine-exposed immunised rats. In conclusion, the present
      results show that immunisation with IP18-KLH did not precipitate nicotine
      withdrawal in rats. Thus, immunisation with IP18-KLH may not elicit nicotine
      withdrawal in smokers either. Furthermore, since the withdrawal syndrome in rats
      was attenuated by immunisation, the nicotine withdrawal in smokers should not be
      worsened but may even be ameliorated during a quit attempt.

PMID- 16292516
TI  - All-trans-retinoic acid suppresses interferon-gamma and tumor necrosis factor
      alpha; a possible therapeutic agent for rheumatoid arthritis.
AB  - OBJECTIVES: To study the effects of all-trans-retinoic acid (ATRA), we determined
      the proliferation and cytokine production by peripheral blood mononuclear cells
      (PBMCs) and CD4+ T cells in healthy volunteers and patients with rheumatoid
      arthritis (RA), and explored the possibility of using ATRA as a therapeutic agent
      for autoimmune diseases. METHODS: Proliferation of these cells was determined by
      modified MTT assay, and expression of CC chemokine receptors 4 (CCR4) and CCR5
      was determined by flow cytometry. Production and expression of interferon (IFN)
      gamma, interleukin (IL)-2, IL-4, and tumor necrosis factor (TNF)-alpha was
      determined by Enzyme-Linked Immunosorbent Assay (ELISA) and reverse transcription
      polymerase chain reaction (RT-PCR). The presence of STAT6 protein was determined
      by Western blot analysis. RESULTS: ATRA did not affect the proliferation or
      production of IL-2 and IL-4. We did not detect STAT6 protein, and saw no evidence
      of the differentiation of PBMCs to Th1 or Th2 cells. In contrast, ATRA suppressed
      the production of IFN-gamma and TNF-alpha significantly. There were no
      significant differences between the healthy volunteers and RA patients.
      CONCLUSIONS: ATRA was demonstrated to affect the cytokine production of IFN-gamma
      and TNF-alpha. ATRA might be useful in the treatment of autoimmune diseases such
      as RA.

PMID- 16292515
TI  - Alpha1-and beta2-adrenoceptors in the human liver with mass-forming intrahepatic
      cholangiocarcinoma: density and coupling to adenylate cyclase and phospholipase
      C.
AB  - Besides the regulation of hepatic metabolic pathways in which adrenoceptors are
      mainly involved, their effect on the second messenger cAMP is thought to be
      related to the growth and differentiation of neoplastic cells. However, few
      studies have been done on the status of these structures in the human liver
      affected by cholangiocarcinoma (CC). Thus, in this study, changes in densities of
      alpha1- and beta2-adrenoceptors (alpha1-and beta2-ARs) were investigated in
      membranes of human liver with cholangiocarcinoma, and for comparison, in
      membranes of non-adjacent non-tumour liver using the potent antagonists [3H]
      prazosin and [1I]-iodocyanopindolol (ICYP) respectively. In addition, the
      activity of membrane-bound phospholipase C (PLC) and adenylate cyclase (AC) was
      also studied. In CC liver, the density of alpha1-and beta2-ARs was significantly
      reduced, compared with non-tumour liver tissues (alpha1-ARs: 23.38+/-4.69 vs
      80.35+/-10.52, P=0.0002 beta2-ARs: 14.27+/-2.93 vs 33.22+/-4.32 fmol/mg protein,
      P=0.03), whereas the ligand affinities (KD) remained unchanged. The beta2
      selective antagonist ICI 118,551 was about 100 times more potent in inhibiting
      ICYP binding than the beta1-selective antagonist CGP 20712A; thus, more than 98%
      of the beta-ARs were of the beta2-subtypes. The AC activity upon stimulants
      acting on beta-AR (isoprenaline), G-protein (GTP, NaF) and AC (forskolin) was
      decreased in CC liver. Similarly, noradrenaline-stimulated PLC activity was
      significantly reduced in tumour tissues. In conclusion, in CC liver the alpha1-
      and beta2-ARs density was down-regulated and the neoplastic invasion blunted AC
      and PLC activity. These quantitative changes may help to elucidate not fully
      understood pathogenetic mechanisms of disturbed hepatic metabolic processes, such
      as hypoglycemia during cancer in human liver.

PMID- 16292517
TI  - A comparative clinical study of short-term results of laparoscopic surgery for
      rectal cancer during the learning curve.
AB  - OBJECTIVES: The aim of this study was to assess the results of laparoscopic
      surgery for rectal carcinoma (LSRC) during the learning curve throughout the
      introduction of this technique at our medical center. MATERIALS AND METHODS: From
      January 2003 to April 2004, 40 patients undergoing surgery were assigned to
      laparoscopic surgery group (LSG) (n=20) or conventional surgery group (CSG)
      (n=20). Data were prospectively collected to statistically analyze clinical,
      anatomopathological, and economic variables. RESULTS: Groups were comparable in
      age, sex, body mass index, American Society of Anesthesiologists score, surgical
      technique performed, tumor size and distance, Dukes' stage, and proportion of
      patients with previous abdominal surgery and radiotherapy. There was no
      difference in operative time. LSG blood loss was lower (p<.0001). LSG peristalsis
      and oral intake began earlier (p<.0001). LSG hospital stay was shorter (p<.0001).
      Intraoperative complications (10% LSG vs 15% CSG) and overall morbidity (35% LSG
      vs 45% CSG) were no different. LSG did not record any anastomotic leakages. Two
      patients (10%) were converted to open surgery. Regarding oncologic adequacy of
      resection, specimen length and number of nodes harvested were no different. LSG
      distal and radial resection margins were greater (p<.0001; p=.03). LSG operative
      costs were greater (p<.0001). However, CSG hospitalization costs were higher
      (p<.001). There was no overall difference (p=0.1). CONCLUSIONS: LSRC has been a
      reliable and efficient technique during the learning curve at our hospital.

PMID- 16292518
TI  - Functional expression of the interleukin-11 receptor alpha-chain in normal
      colonic epithelium and colon cancer.
AB  - BACKGROUND: Interleukin-11 (IL-11) has been evaluated as an anti-inflammatory and
      mucosa-protective therapeutic agent in inflammatory bowel diseases (IBDs).
      Activity of IL-11 requires binding to the alpha receptor subunit (IL-11Ralpha)
      that provides ligand specificity. Recently, we showed that in the intestinal
      mucosa, IL-11Ralpha is mainly present on epithelial cells mediating antiapoptotic
      effects. The aim of this study was to investigate the expression profiling of IL
      11Ralpha and its downstream signaling cascade in colonic adenoma and carcinoma.
      MATERIALS AND METHODS: The expression of IL-11Ralpha in normal colonic mucosa, 11
      colonic adenomas, and 10 carcinomas was analyzed by immunohistochemistry. In
      addition, IL-11Ralpha-expression and IL-11Ralpha-induced phosphorylation of
      signal transducer and activator of transcription (STAT)3 were investigated by
      Western blot analysis. RESULTS: Immunohistochemistry revealed significant IL-11
      Ralpha expression in epithelial cells of normal colonic mucosa. In contrast, the
      expression of IL-11-Ralpha in colon adenomas and carcinomas was either absent or
      only detectable in very few scattered epithelial cells. Densitometric analysis of
      Western blots confirmed these results, showing a decrease of IL-11Ralpha-protein
      in cells isolated from adenomas or carcinomas. Reduced STAT3-phosphorylation in
      carcinoma cells indicated functional consequences of decreased IL-11Ralpha
      protein expression on signal transduction. CONCLUSION: This study demonstrates a
      decrease of IL-11-Ralpha-protein expression in epithelial cells isolated from
      colon carcinomas and adenomas compared to normal colonic mucosa and a reduced
      STAT3 signaling. Because of reduced binding and signal transduction, it is
      unlikely that therapeutically administered IL-11 would contribute to colorectal
      carcinoma induction and growth.

PMID- 16292519
TI  - What do glaucoma specialists know about their patients?
AB  - BACKGROUND: Although interaction between doctor and patient is undoubtedly
      influenced by their mutual expectations, little information is available about
      the knowledge and expectations of glaucoma doctors concerning their patients'
      attitudes and treatment patterns. The aim of our prospective study was to compare
      the actual responses of glaucoma patients concerning various issues related to
      their disease and the responses the glaucoma doctors expected their patients to
      give. METHODS: Glaucoma patients consecutively sent to our glaucoma centre were
      asked to complete a standardised questionnaire about their glaucoma history,
      treatment routines and opinions on issues related to glaucoma. Ophthalmologists
      at the glaucoma centre were asked to predict patients' answers. RESULTS: One
      hundred and twenty-eight consecutive glaucoma patients completed the patients'
      questionnaire and 12 glaucoma specialists completed the corresponding
      questionnaire for doctors. Frequency of intraocular pressure (IOP) measurements
      and visual field testing, as well as the number of topical medications, were
      relatively accurately predicted by the glaucoma doctors. Differences between the
      doctors' predictions and patients' responses were found concerning discomfort
      after surgery and the influence of stress or environmental factors on IOP. The
      largest range of doctors' predictions (0-100%) was observed concerning the
      portion of patients claiming a 100% adherence to glaucoma medication. CONCLUSION:
      Glaucoma specialists are familiar with the treatment patterns of their patients.
      The knowledge of glaucoma specialists of their patients' subjective attitudes to
      glaucoma-related issues deserves further investigation, as discrepancies between
      doctors' and patients' responses were observed in this area.

PMID- 16292520
TI  - Two pathways of apoptosis are simultaneously induced in the embryonal brains of
      neural cell-specific HIF-1alpha-deficient mice.
AB  - The aim of this study was to clarify the mechanism of apoptosis seen in the
      cortex of neural cell-specific hypoxia inducible factor-1alpha (HIF-1alpha)
      deficient embryos. A previous study showed that the neural cells in the cortical
      area of the mutant embryos underwent apoptosis coincident with vascular
      regression. Through histological, immunohistochemical, and electron microscopic
      technique, two kinds of apoptotic cells were detected in the mutant embryonal
      cortex. Apoptotic cells of one type were clustered in small round structures, 10
      20 mum in diameter, whereas the others, present in large numbers, were
      distributed in a group at the cortical plate located more to the outer side than
      the round structures. The histochemical and electron microscopic findings
      indicate that the former represented the appearance of macrophages, in which
      cellular fragments including vascular cells underwent oxidative stress-related,
      TNF receptor-mediated, caspase-2-induced apoptosis, while the latter showed c-Myc
      related, caspase-3-activated apoptosis of the neural cells. These results suggest
      that two pathways of apoptosis are induced in neuronal and vascular cells of the
      cortex in the neural cell-specific HIF-1alpha-deficient mouse.

PMID- 16292521
TI  - The use of drugs with a life-shortening effect in end-of-life care in neonates
      and infants.
AB  - OBJECTIVE: The purpose was to describe the use of drugs with a possible or
      certain life-shortening effect in end-of-life care in infants and to evaluate the
      possibly lethal effect. DESIGN: For 292/298 deaths of live born infants (<1
      year), in a 1-year period (between 1 August 1999 and 31 July 2000) in Flanders,
      Belgium, the attending physician could be identified and was sent an anonymous
      questionnaire. The questionnaires relating to deaths directly preceded by the
      administration of drugs were reviewed by a multi-disciplinary panel. RESULTS: The
      response rate was 86.6% (253/292). In 57 cases (22.5%), drugs were administered
      directly before death. In 17/57 cases, the physician explicitly intended to
      hasten death. In 16/17 cases information about the drug(s) was available: opioids
      were administered in 14, a muscle relaxant in 5 and potassium chloride in 3
      cases. In 13 cases where the lethal effect could be evaluated, the panel judged
      that the drugs were effective in hastening death in 10 cases. In most cases the
      estimated life-shortening was <24 h. In 40/57 cases the physician administered
      drugs to alleviate pain and/or symptoms, taking into account a possible life
      shortening effect without explicitly intending it. Opioids were administered in
      all 30 cases where information about the drug(s) was supplied. In 13 cases the
      lethal effect could be evaluated, and in 6 cases the panel judged that the drugs
      had hastened death. CONCLUSIONS: When life-shortening was explicitly intended,
      (dosages of) drugs were likely to be lethal. Drugs administered also clearly
      hastened death in some cases where life-shortening was not explicitly intended.

PMID- 16292522
TI  - Metabolically active Crenarchaeota in Altamira Cave.
AB  - Altamira Cave contains valuable paleolithic paintings dating back to 15,000
      years. The conservation of these unique paintings is attracting increasing
      interest, and so, understanding microbial proliferation in Altamira Cave
      represents a prioritary objective. Here, we show for the first time that members
      of the Crenarchaeota were metabolically active components of developing microbial
      communities. RNA was extracted directly from the studied environment, and a
      number of 16S rRNA gene sequences belonging to the low-temperature Crenarchaeota
      were detected. Although low-temperature Crenarchaeota detected in a variety of
      ecosystems by using molecular techniques remain uncultured, this RNA-based study
      confirms an active participation of the Crenarchaeota in cave biogeochemical
      cycles.

PMID- 16292523
TI  - Approaches to semi-synthetic minimal cells: a review.
AB  - Following is a synthetic review on the minimal living cell, defined as an
      artificial or a semi-artificial cell having the minimal and sufficient number of
      components to be considered alive. We describe concepts and experiments based on
      these constructions, and we point out that an operational definition of minimal
      cell does not define a single species, but rather a broad family of interrelated
      cell-like structures. The relevance of these researches, considering that the
      minimal cell should also correspond to the early simple cell in the origin of
      life and early evolution, is also explained. In addition, we present detailed
      data in relation to minimal genome, with observations cited by several authors
      who agree on setting the theoretical full-fledged minimal genome to a figure
      between 200 and 300 genes. However, further theoretical assumptions may
      significantly reduce this number (i.e. by eliminating ribosomal proteins and by
      limiting DNA and RNA polymerases to only a few, less specific molecular species).
      Generally, the experimental approach to minimal cells consists in utilizing
      liposomes as cell models and in filling them with genes/enzymes corresponding to
      minimal cellular functions. To date, a few research groups have successfully
      induced the expression of single proteins, such as the green fluorescence
      protein, inside liposomes. Here, different approaches are described and compared.
      Present constructs are still rather far from the minimal cell, and experimental
      as well as theoretical difficulties opposing further reduction of complexity are
      discussed. While most of these minimal cell constructions may represent
      relatively poor imitations of a modern full-fledged cell, further studies will
      begin precisely from these constructs. In conclusion, we give a brief outline of
      the next possible steps on the road map to the minimal cell.

PMID- 16292524
TI  - (-)-Menthol biosynthesis and molecular genetics.
AB  - (-)-Menthol is the most familiar of the monoterpenes as both a pure natural
      product and as the principal and characteristic constituent of the essential oil
      of peppermint (Mentha x piperita). In this paper, we review the biosynthesis and
      molecular genetics of (-)-menthol production in peppermint. In Mentha species,
      essential oil biosynthesis and storage is restricted to the peltate glandular
      trichomes (oil glands) on the aerial surfaces of the plant. A mechanical method
      for the isolation of metabolically functional oil glands, has provided a system
      for precursor feeding studies to elucidate pathway steps, as well as a highly
      enriched source of the relevant biosynthetic enzymes and of their corresponding
      transcripts with which cDNA libraries have been constructed to permit cloning and
      characterization of key structural genes. The biosynthesis of (-)-menthol from
      primary metabolism requires eight enzymatic steps, and involves the formation and
      subsequent cyclization of the universal monoterpene precursor geranyl diphosphate
      to the parent olefin (-)-(4S)-limonene as the first committed reaction of the
      sequence. Following hydroxylation at C3, a series of four redox transformations
      and an isomerization occur in a general "allylic oxidation-conjugate reduction"
      scheme that installs three chiral centers on the substituted cyclohexanoid ring
      to yield (-)-(1R, 3R, 4S)-menthol. The properties of each enzyme and gene of
      menthol biosynthesis are described, as are their probable evolutionary origins in
      primary metabolism. The organization of menthol biosynthesis is complex in
      involving four subcellular compartments, and regulation of the pathway appears to
      reside largely at the level of gene expression. Genetic engineering to up
      regulate a flux-limiting step and down-regulate a side route reaction has led to
      improvement in the composition and yield of peppermint oil.

PMID- 16292525
TI  - Diagnosis of abdominal aortic hypoplasia by state-of-the-art MR angiography.
AB  - Abdominal aortic hypoplasia is a rare vascular variant with possible major
      clinical sequelae when the renal arteries are also involved. The condition is
      thought to result from embryonic overfusion of the two dorsal aortas. The
      diagnosis may be considered in patients presenting with hypertension in the
      neonatal period and severely reduced or absent arterial pulses in the groin. We
      present contrast-enhanced state-of-the-art magnetic resonance angiography imaging
      findings in an 8-year-old boy with abdominal aortic hypoplasia.

PMID- 16292526
TI  - Assessment of lung function in children by cross-sectional imaging: techniques
      and clinical applications.
AB  - Imaging techniques are indispensable for diagnosis and follow-up of paediatric
      pulmonary diseases. In the past, interest was focused on morphological aspects of
      pulmonary tissue. With the development of novel CT and MRI techniques, functional
      pulmonary imaging became available. In this review, the new techniques of cross
      sectional functional imaging of the lung are presented and the value of these
      methods for investigating paediatric pulmonary diseases and their potential
      clinical applications are discussed.

PMID- 16292527
TI  - Relationship between the extracellular polymeric substances and surface
      characteristics of Rhodopseudomonas acidophila.
AB  - The relationship between the extracellular polymeric substances (EPS) and surface
      characteristics of Rhodopseudomonas acidophila in its different growth phases was
      established. The equilibrium constant of partition (K par) and the Gibbs energies
      of partition (DeltaG par) between hexadecane and aqueous phases were also
      calculated according to the microbial adhesion to hexadecane (MATH) testing. The
      EPS content decreased with cultivation time at the logarithmic phase, but kept
      almost unchanged around 22.9 mg g(-1) dry cell at the stationary phase. The EPS
      production of R. acidophila had a significant effect on its surface
      characteristics. The relative hydrophobicity and the K par values of R.
      acidophila before EPS extraction were both lower than those after extraction.
      Both EPS content and ratio of proteins to carbohydrates had a negative effect on
      the water contact angle of the bacterium, but had a positive influence on the
      bacterial surface free energy and its polar component. On the other hand, the EPS
      were not related with MATH% or the Gibbs energy of partition between hexadecane
      and aqueous phase.

PMID- 16292528
TI  - Optimization of the expression of a laccase gene from Trametes versicolor in
      Pichia methanolica.
AB  - A cDNA encoding for laccase (Lcc1) was isolated from the ligninolytic fungus
      Trametes versicolor by reverse transcriptase polymerase chain reaction. The Lcc1
      gene was subcloned into the Pichia methanolica expression vector pMETalphaA and
      transformed into the P. methanolica strains PMAD11 and PMAD16. The extracellular
      laccase activity of the PMAD11 recombinants was found to be 1.3-fold higher than
      that of the PMAD16 recombinants. The identity of the recombinant protein was
      further confirmed by immunodetection using the Western blot analysis. As
      expected, the molecular mass of the mature laccase was 64.0 kDa, similar to that
      of the native form. The effects of copper concentration, cultivation temperature,
      pH and methanol concentration in the BMMY on laccase expression were
      investigated. The laccase activity in the PMAD11 recombinant was up to 12.6 U ml(
      1) by optimization.

PMID- 16292529
TI  - Characterization of four Rhodococcus alcohol dehydrogenase genes responsible for
      the oxidation of aromatic alcohols.
AB  - Four genes were isolated and characterized for alcohol dehydrogenases (ADHs)
      catalyzing the oxidation of aromatic alcohols such as benzyl alcohol to their
      corresponding aldehydes, one from o-xylene-degrading Rhodococcus opacus TKN14 and
      the other three from n-alkane-degrading Rhodococcus erythropolis PR4. Various
      aromatic alcohols were bioconverted to their corresponding carboxylic acids using
      Escherichia coli cells expressing each of the four ADH genes together with an
      aromatic aldehyde dehydrogenase gene (phnN) from Sphingomonas sp. strain 14DN61.
      The ADH gene (designated adhA) from strain TKN14 had the ability to biotransform
      a wide variety of aromatic alcohols, i.e., 2-hydroxymethyl-6-methylnaphthalene, 2
      hydroxymethylnaphthalene, xylene-alpha,alpha'-diol, 3-chlorobenzyl alcohol, and
      vanillyl alcohol, in addition to benzyl alcohol with or without a hydroxyl,
      methyl, or methoxy substitution. In contrast, the three ADH genes of strain PR4
      (designated adhA, adhB, and adhC) exhibited lower ability to degrade these
      alcohols: these genes stimulated the conversion of the alcohol substrates by only
      threefold or less of the control value. One exception was the conversion of 3
      methoxybenzyl alcohol, which was stimulated sevenfold by adhB. A phylogenetic
      analysis of the amino acid sequences of these four enzymes indicated that they
      differed from other Zn-dependent ADHs.

PMID- 16292530
TI  - Purification and characterization of the glucoside 3-dehydrogenase produced by a
      newly isolated Stenotrophomonas maltrophilia CCTCC M 204024.
AB  - A soluble glucoside 3-dehydrogenase (G3DH) from Stenotrophomonas maltrophilia
      CCTCC M 204024, recently isolated from wheat soil in our laboratory, was purified
      to 37.4-fold with a yield of 24.7% and was estimated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis with a molecular mass of 66 kDa. 2,6
      Dichlorophenolindophenol (DCPIP) and ferricyanide were able to act as artificial
      electron acceptors for the enzyme. The optimal pH of G3DH was in the range of 6.0
      7.0 in the presence of DCPIP. The enzyme was stable in the pH range of 4.4-10.6
      and was sensitive to heat. G3DH exhibited extremely broad substrate specificity
      by converting many sugars to their corresponding 3-ketoglucosides. They produced
      a characteristic spectrum by alkaline treatment with a peak at 340 nm. The
      apparent Km values for validoxylamine A and D: -glucose were 8.3 and 1.1 mM,
      respectively. Cu2+, Ag2+, and Hg2Cl2 inhibited the activity of G3DH.

PMID- 16292532
TI  - Changes in bacterial community structure correlate with initial operating
      conditions of a field-scale denitrifying fluidized bed reactor.
AB  - High levels of nitrate are present in groundwater migrating from the former waste
      disposal ponds at the Y-12 National Security Complex in Oak Ridge, TN. A field
      scale denitrifying fluidized bed reactor (FBR) was designed, constructed, and
      operated with ethanol as an electron donor for the removal of nitrate. After
      inoculation, biofilms developed on the granular activated carbon particles.
      Changes in the bacterial community of the FBR were evaluated with clone libraries
      (n = 500 partial sequences) of the small-subunit rRNA gene for samples taken over
      a 4-month start-up period. Early phases of start-up operation were characterized
      by a period of selection, followed by low diversity and predominance by Azoarcus
      like sequences. Possible explanations were high pH and nutrient limitations.
      After amelioration of these conditions, diversification increased rapidly, with
      the appearance of Dechloromonas, Pseudomonas, and Hydrogenophaga sequences.
      Changes in NO3, SO4, and pH also likely contributed to shifts in community
      composition. The detection of sulfate-reducing-bacteria-like sequences closely
      related to Desulfovibrio and Desulfuromonas in the FBR have important
      implications for downstream applications at the field site.

PMID- 16292531
TI  - Molecular cloning of the gene encoding beta-1,3(4)-glucanase A from a marine
      bacterium, Pseudomonas sp. PE2, an essential enzyme for the degradation of
      Pythium porphyrae cell walls.
AB  - The beta-1,3(4)-glucanase A (GluA)-encoding gene named gluA was cloned from the
      genomic library of a marine bacterium Pseudomonas sp. PE2 by expression in
      Escherichia coli, and the complete DNA sequence was determined. The recombinant
      enzyme from Pseudomonas sp. PE2 was examined to determine the essential enzymes
      for degrading Pythium porphyrae cell walls, comparatively using other two
      recombinant enzymes, chitinase A and beta-1,3-glucanase B from the same bacterial
      strain. GluA most degraded the cell walls among these three enzymes, suggesting
      that GluA seems to be most important to P. porphyrae cell-wall-degrading
      activity. The deduced GluA is a modular enzyme composed of an N-terminal signal
      peptide, the tandem-duplicated carbohydrate-binding module family 6 (CBM(GluA)-1
      and CBM(GluA)-2), and a glycoside hydrolase family 16 catalytic domain. Deletion
      analysis clearly indicated that GluA lacking CBM(GluA)-1 and CBM(GluA)-2 does not
      bind to Avicel and xylan. These results suggest that the tandem-repeated CBM of
      GluA may play a key role in the binding of Avicel and xylan as well as beta-1,3-
      and beta-1,3;1,4-glucans and is very important to bind to insoluble
      polysaccharides.

PMID- 16292533
TI  - Synergy between xylanases from glycoside hydrolase family 10 and family 11 and a
      feruloyl esterase in the release of phenolic acids from cereal arabinoxylan.
AB  - The bioconversion of waste residues (by-products) from cereal processing
      industries requires the cooperation of enzymes able to degrade xylanolytic and
      cellulosic material. The type A feruloyl esterase from Aspergillus niger, AnFaeA,
      works synergistically with (1-->4)-beta-D-xylopyranosidases (xylanases) to
      release monomeric and dimeric ferulic acid (FA) from cereal cell wall-derived
      material. The esterase was more effective with a family 11 xylanase from
      Trichoderma viride in releasing FA and with a family 10 xylanase from Thermoascus
      aurantiacus in releasing the 5,5' form of diferulic acid from arabinoxylan (AX)
      derived from brewers' spent grain. The converse was found for the release of the
      phenolic acids from wheat bran-derived AXs. This may be indicative of
      compositional differences in AXs in cereals.

PMID- 16292534
TI  - Increase in hyaluronic acid production by Streptococcus equi subsp. zooepidemicus
      strain deficient in beta-glucuronidase in laboratory conditions.
AB  - Streptococcus equi subsp. zooepidemicus is known to produce a hyaluronic acid
      capsule to resist the host immune defense. As the structure of the polysaccharide
      is identical to the one produced by humans, the bacteria S. equi subsp.
      zooepidemicus is used in biotechnological production of hyaluronic acid. In our
      laboratory we prepared mutated strains that are beta-glucuronidase deficient.
      Comparing the wild-type strain, which is positive in beta-glucuronidase activity,
      with the mutated strains named clone1 and clone2 in laboratory conditions, we
      observed that beta-glucuronidase influences the production of hyaluronic acid
      considerably and the molecular weight of hyaluronan slightly. The production of
      hyaluronic acid by the mutated strains is higher by approximately 20% and the
      molecular weight is larger by about 2%. The significant increase in the
      production of hyaluronic acid and the slight increase in the molecular weight are
      probably caused by an absence of free beta-glucuronic acid, due to its removal
      from the non-reducing termini of the polysaccharide by beta-glucuronidase. The
      presence of free beta-glucuronic acid would likely induce the expression of the
      beta-glucuronic-acid-utilizing operon, which in turn would reflect into a misuse
      of energy in the glucose-rich media.

PMID- 16292535
TI  - Effect of expressing polyhydroxybutyrate synthesis genes (phbCAB) in
      Streptococcus zooepidemicus on production of lactic acid and hyaluronic acid.
AB  - Hyaluronic acid (HA) has been industrially produced using the gram-positive
      bacterium Streptococcus zooepidemicus. Large amount of lactic acid formation was
      one of the important factors that restricted cell growth and HA productivity and
      lowered the substrate to HA conversion efficiency in a fermentor. In this study,
      polyhydroxybutyrate (PHB) synthesis genes (phbCAB) of Ralstonia eutropha were
      cloned from the plasmid pBHR68 and were inserted into the plasmid pEU308, an
      expression vector for gram-positive bacteria. The plasmid was transformed into S.
      zooepidemicus by electroporation. beta-Ketothiolase (PhbA), acetoacetyl-CoA
      reductase (PhbB), and polyhydroxyalkanoate (PHA) synthase (PhbC) activity assays
      were carried out to demonstrate the expression of these genes. The PhbA and PhbB
      activities were 3.13 and 1.23 U mg(-1), respectively. No PhbC activities were
      detected. In shake flask studies, there was no obvious difference between the
      wild-type and recombinant S. zooepidemicus harboring phbCAB genes in terms of
      lactic acid and HA formation. However, in fermentor studies, the recombinant
      produced only 40 g L(-1) lactic acid and 7.5 g L(-1) HA, whereas the wild type
      produced 65 g L(-1) lactic acid and 5.5 g L(-1) HA. These results suggested that
      expression of phbCAB genes in S. zooepidemicus could help regulate HA production
      metabolism. Because the lactic acid formation in S. zooepidemicus was sensitive
      to cellular oxidation/reduction potential, it is proposed that the PHB synthesis
      pathway could act as a regulator to adjust the cellular oxidation/reduction
      potential. This is the first study demonstrating that PHA synthesis related to
      energy and carbon metabolism could be employed as a pathway to regulate other
      cellular metabolism and possibly to regulate the production of other metabolic
      products.

PMID- 16292536
TI  - Toxic death-case after capecitabine + oxaliplatin (XELOX) administration:
      probable implication of dihydropyrimidine deshydrogenase deficiency.
AB  - This report here is the case of a 52-year-old male patient who suffered from
      extremely severe haematological toxicities (G4 neutropenia, G4 thrombocytopenia)
      while undergoing Xelox (Xeloda + Oxaliplatin) treatment for his multifocal
      hepatocarcinoma. Despite appropriate supportive treatment, his condition quickly
      deteriorated and led to death. It was hypothesized that dihydropyrimidine
      deshydrogenase (DPD) gene polymorphism could be, at least in part, responsible
      for this fatal outcome. To test this hypothesis, both phenotypic and genotypic
      studies were undertaken, and fully confirmed the DPD-deficient status of this
      patient. Uracil to dihydrouracil ratio in plasma was evaluated as a surrogate
      marker for DPD deficiency, and showed values out of the range previously recorded
      from a reference, non-toxic population. Interestingly, the canonical IVS14+1G>A
      single nucleotide polymorphism, usually associated with the most severe
      toxicities reported with 5-fluorouracil (5-FU), was not found in this patient,
      but further investigations showed instead a heterozygosity for the 1896C>T
      mutation located in the exon 14 of the DPYD gene. Taken together, the data
      strongly suggest for the first time that a toxic-death case after capecitabine
      containing protocol could be, at least in part, linked with a DPD-deficiency
      syndrome. The case reported here warrants therefore systematic detection of
      patients at risk, including when oral capecitabine is scheduled.

PMID- 16292537
TI  - Bortezomib interactions with chemotherapy agents in acute leukemia in vitro.
AB  - Although there is effective chemotherapy for many patients with leukemia, 20% of
      children and up to 65% of adults relapse. Novel therapies are needed to treat
      these patients. Leukemia cells are very sensitive to the proteasome inhibitor
      bortezomib (VELCADE(R), PS-341), which enhances the in vitro cytotoxic effects of
      dexamethasone and doxorubicin in multiple myeloma. To determine if bortezomib
      enhances the cytotoxicity of agents used in leukemia, we employed an in vitro
      tetrazolium-based colorimetric assay (MTT) to evaluate the cytotoxic effects of
      bortezomib alone and in combination with dexamethasone, vincristine, doxorubicin,
      cytarabine, asparaginase, geldanamycin, trichostatin A, and the bcl-2 inhibitor
      HA14.1. We demonstrated that primary leukemia lymphoblasts and leukemia cell
      lines are sensitive to bortezomib, with an average IC(50) of 12 nM. Qualitative
      and quantitative bortezomib-drug interactions were evaluated using the universal
      response surface approach (URSA). Bortezomib was synergistic with dexamethasone
      in dexamethasone-sensitive leukemia cells, and additive with vincristine,
      asparaginase, cytarabine, and doxorubicin. The anti-leukemic activity of
      bortezomib was also additive with geldanamycin and HA14.1, and additive or
      synergistic with trichostatin A. These results were compared to analysis using
      the median-dose effect method, which generated complex drug interactions due to
      differences in dose-response curve sigmoidicities. These data suggest bortezomib
      could potentiate the cytotoxic effects of combination chemotherapy in patients
      with leukemia.

PMID- 16292538
TI  - Human breast cell lines exhibit functional alpha2-adrenoceptors.
AB  - Adrenergic compounds (epinephrine and norepinephrine) are the most important
      hormones released during stress. Several different receptors are associated with
      their action in different tissues. However, alpha(2)-adrenoceptors have not yet
      been described in either normal or tumour human breast tissue. The aim of this
      work was to describe and characterize these receptors in several tumour and non
      tumour human cell lines. The expression of alpha(2)-adrenoceptors was analyzed at
      the RNA (RT-PCR) and protein ([(3)H]-rauwolscine binding and immunocytochemistry)
      levels in different human breast cell lines, and the biological activity assessed
      by [(3)H]-thymidine incorporation. The cancer IBH-6, IBH-7 and MCF-7 and the non
      tumour HBL-100 cells line, expressed both alpha(2B)- and alpha(2C)-adrenoceptor
      subtypes. A single subtype was expressed in malignant HS-578T (alpha(2A)) and MDA
      MB-231 and non-tumour MCF-10A cells (alpha(2B)). All cell lines exhibited
      significant binding for the specific antagonist [(3)H]-rauwolscine. The alpha-,
      alpha(2)-, and the alpha(1)-compounds with known affinity for alpha(2)
      adrenoceptors, including epinephrine, norepinephrine, yohimbine, clonidine,
      rauwolscine and prazosin, competed significantly with binding in MCF-7 cells. In
      addition, IBH-6, IBH-7 and MCF-7 cells showed significant staining with specific
      antibodies against alpha(2B)- and alpha(2C)-adrenoceptor-subtypes, when tested by
      immunocytochemistry. In all cell lines, the specific agonist clonidine or
      oxymetazoline stimulated [(3)H]-thymidine incorporation. EC(50) values were in
      the range of 20-50 fM for IBH-6, IBH-7, and HS-578T; 0.14 pM for MCF-7; 2-82 pM
      for HBL-100 and MCF-10A cells, and a biphasic behaviour with a maximum value at
      38.0 pM, was observed for MDA-MB-231 cells. The specific alpha(2)-adrenergic
      antagonist rauwolscine always reversed this stimulation at 0.1 nM. In conclusion,
      this study describes for the first time, the presence of alpha(2)-adrenoceptors
      in human epithelial breast cell lines. Moreover, activation of these receptors
      was associated with an enhancement of cell proliferation.

PMID- 16292539
TI  - Parameters affecting the efficiency of Agrobacterium tumefaciens-mediated
      transformation of Colletotrichum graminicola.
AB  - We have developed an Agrobacterium tumefaciens-mediated transformation (ATMT)
      protocol for the plant pathogenic fungus Colletotrichum graminicola, the cause of
      anthracnose leaf blight and stalk rot of corn. The ATMT results in higher
      transformation efficiencies than previously available polyethylene glycol
      mediated protocols, and falcate spores can be used instead of protoplasts for
      transformation. Various experimental parameters were tested for their effects on
      transformation efficiencies. The parameters with the greatest influence were the
      A. tumefaciens strain used and the Ti-plasmid it carried, the ratio of bacterium
      to fungus during cocultivation, and the length of cocultivation. Southern
      analysis demonstrated that most transformants (80%) contained tandem integrations
      of plasmid sequences, and at least 36% had integrations at multiple sites in the
      genome. In a majority of cases (70%), the whole Ti-plasmid, and not just the T
      DNA, had integrated as a series of tandem repeats. Tandem integrations,
      especially of the whole plasmid, make it difficult to rescue DNA from both flanks
      of the integrations with standard PCR-based approaches. Thus, ATMT may be
      unsuitable for insertional mutagenesis of C. graminicola without further
      modification.

PMID- 16292540
TI  - Thyroid hormone-induced expression of a bZip-containing transcription factor
      activates epithelial cell proliferation during Xenopus larval-to-adult intestinal
      remodeling.
AB  - In the intestine during amphibian metamorphosis, stem cells appear, actively
      proliferate, and differentiate into an adult epithelium analogous to the
      mammalian counterpart. To clarify the molecular mechanisms regulating this
      process, we focused on a bZip-containing transcription factor (TH/bZip). We
      previously isolated TH/bZip from the Xenopus intestine as one of the candidate
      genes involved in adult epithelial development. Northern blot and in situ
      hybridization analyses showed that the transient and region-dependent expression
      of TH/bZip mRNA correlates well with the growth of adult epithelial primordia
      originating from the stem cells throughout the Xenopus intestine. To investigate
      its role in the adult epithelial development, we established an in vitro gene
      transfer system by using electroporation and organ culture techniques, and we
      overexpressed TH/bZip in the epithelium of Xenopus tadpole intestines. In the
      presence of thyroid hormone (TH) where the adult epithelial primordia appeared
      after 3 days of cultivation, overexpression of TH/bZip significantly increased
      their proliferating activity. On the other hand, in the absence of TH where the
      epithelium remained as larval-type without any metamorphic changes, ectopic
      expression of TH/bZip significantly increased the proliferating activity of the
      larval epithelium but had no effects on its differentiated state. These results
      indicate that TH/bZip functions as a growth activator during amphibian intestinal
      remodeling, although TH/bZip expression in the epithelium alone is not sufficient
      for inducing the stem cells.

PMID- 16292541
TI  - MYH Y165C and G382D mutations in hepatocellular carcinoma and cholangiocarcinoma
      patients.
AB  - PURPOSE: Production of reactive oxygen species (ROS) during chronic inflammation
      has been implicated in the progression of liver diseases and carcinogenesis.
      Subjects with inflammatory liver disease and one non-functional allele of the
      base excision repair gene, MYH, may be more susceptible to progression to cancer
      due to MYH haploinsufficiency in repairing oxidative damage caused by ROS. Here,
      we investigated the association of two common germline MYH mutations in patients
      with hepatocellular carcinoma (HCC) and cholangiocarcinoma. METHODS: DNA from
      patients with HCC (n=48) or cholangiocarcinoma (n=84) compared to non-cancerous
      controls (n=308) were genotyped for the Y165C and G382D mutations in MYH.
      RESULTS: There was no significant difference in MYH mutation carrier status
      between patients with HCC (1/48), cholangiocarcinoma (3/84), and non-cancerous
      controls (4/308). CONCLUSIONS: Patients with HCC or cholangiocarcinoma do not
      have an increased incidence of monoallelic MYH mutations pre-disposing them to
      disease.

PMID- 16292542
TI  - Phase-I/II study to evaluate dose limiting toxicity, maximum tolerated dose, and
      tolerability of bendamustine HCl in pre-treated patients with B-chronic
      lymphocytic leukaemia (Binet stages B and C) requiring therapy.
AB  - PURPOSE: Bendamustine hydrochloride, an anti-neoplastic agent with unique
      mechanism of action, is known to cause impressive remissions in relapsed non
      Hodgkin's lymphoma and chronic lymphocytic leukaemia (CLL). Optimal bendamustine
      dosing for CLL patients had not been finally established and a phase I/II study
      was conducted to determine the maximum tolerated dose (MTD) and dose limiting
      toxicity (DLT) of bendamustine. METHODS: The open-label, single-centre phase I/II
      study was conducted from March 2001 to September 2002 in Sofia, Bulgaria. The 15
      study patients were extendedly pre-treated, but fludarabine-naive (3 female, 12
      male, 47-72 years of age, 61 years on average). Bendamustine was given at a
      starting dose of 100 mg/m2 on days 1 and 2 every 3 weeks based on the previous
      results in lymphoma. RESULTS: Bendamustine was well tolerated in spite of heavy
      pre-treatment of the study participants. Toxicity corresponded to the known
      safety profile of bendamustine, with the exception of bilirubin elevation. The
      level of 110 mg/m2 was established as MTD. A bendamustine dose of 100 mg/m2 is
      the recommended dose for further clinical investigations. A 4-week interval is
      recommended to allow for sufficient recovery. Efficacy results confirmed powerful
      anti-neoplastic activity of bendamustine even in extendedly pre-treated CLL
      patients. Based on the remission criteria, nine patients were defined as
      responders (four CRs, two PR, three NC) and two patients as nonresponders to
      therapy. Four patients were not evaluable for response, because they had received
      less than three courses bendamustine. After a follow-up period of 15 months, the
      four patients with CR were still in remission. One patient with PR had relapsed,
      the other had ongoing response. CONCLUSIONS: Bendamustine is a very active and
      well-tolerated drug in patients with pre-treated and refractory CLL. Fludarabine
      naivity of patients appears to markedly improve their bendamustine tolerability.
      First-line use of bendamustine is a safe option for CLL-patients requiring
      treatment, because bendamustine-owing to its unique pharmacodynamics-(1) is
      highly effective, (2) reasonably safe, and (3) does hardly produce cross
      resistance against other anti-neoplastic drugs effective in this indication.

PMID- 16292543
TI  - Associating phenotypes with molecular events: recent statistical advances and
      challenges underpinning microarray experiments.
AB  - Progress in mapping the genome and developments in array technologies have
      provided large amounts of information for delineating the roles of genes involved
      in complex diseases and quantitative traits. Since complex phenotypes are
      determined by a network of interrelated biological traits typically involving
      multiple inter-correlated genetic and environmental factors that interact in a
      hierarchical fashion, microarrays hold tremendous latent information. The
      analysis of microarray data is, however, still a bottleneck. In this paper, we
      review the recent advances in statistical analyses for associating phenotypes
      with molecular events underpinning microarray experiments. Classical statistical
      procedures to analyze phenotypes in genetics are reviewed first, followed by
      descriptions of the statistical procedures for linking molecular events to
      measured gene expression phenotypes (microarray-based gene expression) and
      observed phenotypes such as diseases status. These statistical procedures include
      (1) prior analysis, such as data quality controls, and normalization analyses for
      minimizing the effects of experimental artifacts and random noise; (2) gene
      selections and differentiation procedures based on inferential statistics for the
      class comparisons; (3) dynamic temporal patterns analysis through exploratory
      statistics such as unsupervised clustering and supervised classification and
      predictions; (4) assessing the reliability of microarray studies using real-time
      PCR and the reproducibility issues from many studies and multiple platforms. In
      addition, the post analysis to associate the discovered patterns of gene
      expression to pathway and functional analysis for selected genes are also
      considered in order to increase our understanding of interconnected gene
      processes.

PMID- 16292544
TI  - Detection and monitoring of cerebral hemodynamic disturbances with transcranial
      color-coded duplex sonography in patients after head injury.
AB  - Reduced cerebral blood flow after severe head injury results in an increased risk
      of ischemic brain damage. Blood flow should therefore be monitored with a simple,
      reliable method. Transcranial color-coded Doppler sonography (TCCS) is an
      accepted tool for the diagnosis of cerebral vasospasm; however, its usefulness in
      evaluating patients with head injury has not been proven. Cerebral blood-flow
      velocity in the middle, anterior, and posterior cerebral arteries was measured
      with a 2.5 MHz probe (Aplio SSA 770A, Toshiba, Japan) in 36 subjects with
      moderate or severe head injury. Serial measurements of resistance index (RI),
      peak-systolic, end-diastolic, and mean velocity in the middle cerebral arteries
      were performed 2-24 h after head trauma and in the subsequent days during
      hospitalization. Immediately after head trauma, increased RI values, and
      unusually decreased blood-flow velocity (mainly in MCA) were observed.
      Microcirculation disturbances were suspected because the end-diastolic velocity
      had substantially diminished. Changes in blood-flow parameters correlated with
      the clinical state, and in most cases, a poor prognosis. In some patients, blood
      flow velocity increased above the normal reference limit and this implied poor
      prognosis. Transcranial color-coded Doppler sonography is a reliable, repeatable,
      and accessible tool that provides information about cerebral blood-flow
      disturbances and may hold diagnostic and prognostic importance.

PMID- 16292545
TI  - Evolving radiological features of hypothalamo-pituitary lesions in adult patients
      with Langerhans cell histiocytosis (LCH).
AB  - Langerhans cell histiocytosis (LCH) is a rare, systemic disease caused by
      monoclonal expansion of dendritic cells that shows a particular predilection for
      the hypothalamic-pituitary system (HPS). We studied the function (anterior and
      posterior pituitary hormonal secretion) and morphology using magnetic resonance
      imaging (MRI) of the HPS in 17 adult patients (seven males, median age 35 years,
      range 18-59 years) with multisystem LCH. We also evaluated the evolution of
      structural HPS abnormalities in relation to pituitary function and response to
      treatment in 12 of these patients during a median follow-up period of 3.75 years
      (range 1.5-10 years). Of the 17 patients, 14 (82%) had abnormal HPS imaging, and
      12 (70%) had more than one area involved. Lack of the bright spot of the
      posterior pituitary lobe was typically found in all patients with the diagnosis
      of diabetes insipidus (DI). Eight patients (47%) had infundibular enlargement,
      six (35%) pituitary infiltration, four (24%) partially or completely empty sella,
      three (18%) hypothalamic involvement, and two (12%) infundibular atrophy. DI was
      found in 16 patients (94%) and anterior pituitary hormonal deficiency (APHD) in
      10 patients (59%); two patients had single (12%) and 8 (47%) multiple APHD.
      During the follow-up period there was improvement of the initially demonstrated
      HPS pathology in seven (47%) patients, and five (33%) of them had received at
      least one form of treatment. APHD and DI persisted in all patients except in one
      in whom established gonadotrophin deficiency recovered. In summary, DI and APHD
      are very common in patients with multisystem LCH and are almost always associated
      with abnormal HPS imaging.

PMID- 16292547
TI  - Process analytical chemistry.

PMID- 16292546
TI  - Establishment of signal-recovery functions for calculation of recovery factor.
      Application to monitoring of contaminant residues in vegetables by
      chemiluminescence detection.
AB  - A new strategy is proposed for verifying if recovery factor is constant and
      independent of the real analyte content of samples. A signal-recovery function
      has been developed on the basis of measurement of spiked test samples before and
      after a pre-treatment step and considering, as starting point, a recent IUPAC
      recommendation which distinguishes between two terms--recovery factor, R, and
      apparent recovery, R*. Apparent recovery includes recovery factor and a new
      recovery term proposed in a previous paper by the authors, named calibration
      recovery, R(C). The signal-recovery function is obtained directly from the
      measured analytical signals instead of from the concentrations, simplifying the
      calculations. A linear signal-recovery curve indicates that the recovery factor
      is constant in the analyte concentration range studied experimentally and, in
      this way, a single recovery factor can be calculated. The usefulness of the
      proposed method has been shown by quantification of the pesticide carbaryl by two
      different flow-injection analysis methods with chemiluminescent detection based
      on the luminol and TCPO systems. Good results were obtained from both methods.

PMID- 16292548
TI  - Automatic determination of phylloquinone in vegetables and fruits using on-line
      photochemical reduction and fluorescence detection via solid phase extraction and
      flow injection.
AB  - A very simple, rapid and highly sensitive flow injection fluorimetric method was
      developed for the determination of phylloquinone. The assay was based on the on
      line reduction of phylloquinone in dodecylsulfate micelles after irradiation with
      UV light. The micellar medium enhanced the fluorescence and stability of the
      reduced phylloquinone. Under optimum experimental conditions, the range of
      application of the technique was between 0.09 and 45.0 microg mL(-1) and the
      detection limit was 0.05 microg mL(-1). The sample throughput was 90 injections
      per hour. The reliability of the method for the routine analysis of phylloquinone
      in vegetables and fruits is demonstrated. Extractions were made with hexane, and
      an automated solid phase extraction system was used to purify the sample extracts
      prior to injection into the flow injection manifold.

PMID- 16292549
TI  - In vivo effects of decitabine in myelodysplasia and acute myeloid leukemia:
      review of cytogenetic and molecular studies.
AB  - Low-dose demethylating agents such as 5-aza-2'-deoxycytidine (decitabine, DAC)
      and 5-azacytidine (azacitidine, Vidaza) have been explored for the treatment of
      myelodysplasia, acute myeloid leukemia, and hemoglobinopathies since the early
      1980s, aiming to revert a methylator phenotype. Originally, the treatment
      rationale in hemoglobinopathies was to achieve demethylation of the
      hypermethylated and hence silent gamma-globin gene locus, thus reactivating
      synthesis of hemoglobin F (HbF). In myelodysplastic syndrome (MDS), cytogenetic
      analyses are mandatory for risk stratification and for monitoring response to
      drug treatment. The current knowledge regarding cytogenetic subgroups as
      predictors of response to low-dose decitabine in MDS as well as cytogenetic
      responses caused by demethylating agents is summarized in this review. Decitabine
      treatment is associated with a response rate that is higher in patients with high
      risk cytogenetics (i.e., complex karyotype and/or abnormalities of chromosome 7)
      than in patients with intermediate-risk cytogenetics (two abnormalities or single
      abnormalities excluding 5q-, 20q-, and -Y). Following decitabine treatment of
      patients with abnormal karyotype, approximately one-third achieve a major
      cytogenetic response that can be confirmed by FISH analyses, while in two-thirds
      of patients, the abnormal karyotype persists but hematologic improvement may be
      observed during continued treatment. The most frequently studied gene in
      myelodysplasia is the cell cycle regulator p15(INK4b). Hypermethylation of
      p15(INK4b) in MDS is reversed during treatment with decitabine, resulting in
      reactivation of this gene. In hemoglobinopathies, treatment with demethylating
      agents leads to reactivation of fetal HbF (the gamma-globin gene locus also
      possibly being another target for reactivation in MDS), and thus, HbF may
      potentially act as surrogate marker for activity of decitabine. Other, thus far
      unidentified hypermethylated genes may also be targets for demethylating agents.

PMID- 16292550
TI  - Successful treatment of thrombocytopenia in primary antiphospholipid antibody
      syndrome with the anti-CD20 antibody rituximab--monitoring of antiphospholipid
      and anti-GP antibodies: a case report.

PMID- 16292551
TI  - Seasonal cycle in vitamin A1/A2-based visual pigment composition during the life
      history of coho salmon (Oncorhynchus kisutch).
AB  - Microspectrophotometry of rod photoreceptors was used to follow variations in
      visual pigment vitamin A1/A2 ratio at various life history stages in coho salmon.
      Coho parr shifted their A1/A2 ratio seasonally with A2 increasing during winter
      and decreasing in summer. The cyclical pattern was statistically examined by a
      least-squares cosine model, fit to the 12-month data sets collected from
      different populations. A1/A2 ratio varied with temperature and day length. In 1+
      (>12 month old) parr the A2 to A1 shift in spring coincided with smoltification,
      a metamorphic transition preceding seaward migration in salmonids. The
      coincidence of the shift from A2 to A1 with both the spring increase in
      temperature and day length, and with the timing of seaward migration presented a
      challenge for interpretation. Our data show a shift in A1/A2 ratio correlated
      with season, in both 0+ (<12 months old) coho parr that remained in fresh water
      for another year and in oceanic juvenile coho. These findings support the
      hypothesis that the A1/A2 pigment pair system in coho is an adaptation to
      seasonal variations in environmental variables rather than to a change associated
      with migration or metamorphosis.

PMID- 16292552
TI  - Expression of Connexin 43 in the hearts of rat embryos exposed to nitrofen and
      effects of vitamin A on it.
AB  - Rats with experimental congenital diaphragmatic hernia (CDH) have heart
      hypoplasia and conotruncal and great vessel malformations that are likely related
      to disturbed neural crest developmental control. Neural crest cells communicate
      through intercellular gap junctions whose main protein is Connexin 43 (Cx43). The
      migration and participation of neural crest cells in heart development is likely
      influenced by this protein which might be also directly involved in myocardial
      development. Vitamin A is beneficial for heart hypoplasia in CDH rats. The aims
      of this study were to examine the status of Cx43 in the heart of embryonal rats
      exposed to nitrofen and to assess if vitamin A reverts these effects. Pregnant
      rats received either 100 mg nitrofen or olive oil on E9.5. Each group was divided
      into two subgroups according to the subsequent treatment with intragastric
      vitamin A (15,000 i.u.) or vehicle on E10.5 and E11.5. The pups were recovered on
      E13, E15, and E21 and the hearts were dissected out and pooled. Cx43 mRNA
      expression was determined by quantitative real-time PCR. Comparisons among groups
      were made with ANOVA and Bonferroni post hoc tests with a threshold of
      significance of P<0.05. In control rats Cx43 mRNA was minimally expressed on E13
      and E15 and fully expressed on E21. Nitrofen significantly increased Cx43 mRNA on
      E15. Additional treatment with vitamin A tended to moderate this increase on E15.
      Cx43 was overexpressed in the hearts of nitrofen-exposed embryonal rats on day
      E15 of gestation. Vitamin A tended to normalize this expression. The mechanism of
      action of Cx43 deserves further investigation.

PMID- 16292553
TI  - Sequence preference in DNA binding: de novo designed helix-turn-helix
      metallopeptides recognize a family of DNA target sites.
AB  - The DNA-binding behavior and target sequences of two designed metallopeptides
      have been investigated with an iterative electrophoresis mobility shift assay
      followed by PCR amplification, and by circular dichroism spectroscopy. Peptides
      P3W and P5b were designed based on the structural similarity of the helix-turn
      helix motif of homeodomains and the EF-hand motifs of calmodulin, as previously
      described for P3W. Like P3W, P5b binds both Eu(III) (K(d) = 12.6 +/- 1.9 microM)
      and Ca(II) (K(d) = 70 +/- 8 microM) with reasonable affinity. Binding selection
      from a library of randomized 8-mer DNA oligonucleotide sequences identified one
      target family for CaP5b [5'-pur-T-pur-G-(G/C)-3'], and two target sites for CaP3W
      [5'-(A/T)-G-G-G-(T/C)-3' and 5'-A-T-(G/T)-T-G-3']. Circular dichroism studies
      indicate that unlike EuP3W, EuP5b is poorly folded in the absence of DNA. In the
      presence of DNA containing target-binding sites for both peptides, both EuP3W and
      EuP5b increase in helical content, in the latter case significantly. These
      results suggest that EuP5b binding to target DNA involves an induced-fit
      mechanism. These small chimeric metallopeptides have been found to bind
      selectively to DNA targets, analogous to natural protein-DNA interactions. This
      corroborates our earlier conclusions (J. Am. Chem. Soc. 125:6656, 2003) that
      sequence-preferential DNA cleavage by Ce(IV)P3W was due to sequence recognition.

PMID- 16292554
TI  - Detoxification of the organophosphate nerve agent coumaphos using
      organophosphorus hydrolase immobilized on cellulose materials.
AB  - Neurotoxic organophosphates (OPs) are widely used as pesticides and for public
      health purposes, as well as being nerve gases. As a result of the widespread use
      of these compounds for agriculture, large volumes of wastewater are generated.
      Additionally, there are large stockpiles of the nerve gases soman, sarin and VX
      in the United States and elsewhere around the world. Organophosphorus hydrolase
      (OPH) is an enzyme that catalyzes the hydrolysis of OP nerve agents. To date,
      however, the use of this enzyme in detoxification processes has been rather
      limited due to the high cost of its purification and short catalytic half-life.
      This paper reports the development of a cost-effective method for the production
      and immobilization of OPH in a pilot application in an enzyme bioreactor column
      for detoxification of paraoxon and coumaphos in contaminated wastewaters. A
      fusion between OPH and a cellulose binding domain that binds selectively to
      cellulose was generated to allow one-step purification and immobilization of OPH
      on cheap and abundantly available cellulose immobilization matrices. When packed
      in a column bioreactor, the immobilized fusion enzyme was able to completely
      degrade coumaphos up to a concentration of 0.2 mM. However, stirring of OPH
      immobilized on cellulose materials resulted in complete OP degradation of 1.5 mM
      coumaphos. The bioreactor column degraded the compounds tested at high
      concentration, rapidly, and without loss of process productivity for about 2
      months.

PMID- 16292555
TI  - Occurrence and characterization of actinobacteria and thermoactinomycetes
      isolated from pulp and board samples containing recycled fibres.
AB  - The aim of this study was to characterize the actinobacterial population present
      in pulps and boards containing recycled fibres. A total of 107 isolates was
      identified on the basis of their pigmentation, morphological properties, fatty
      acid profiles and growth temperature. Of the wet pulp and water sample isolates
      (n=87), 74.7% belonged to the genus Streptomyces, 17.2% to Nocardiopsis and 8.0%
      to thermoactinomycetes, whereas all the board sample isolates (n=20) were
      thermoactinomycetes. The identification of 53 isolates was continued by molecular
      methods. Partial 16S rDNA sequencing and automated ribotyping divided the
      Streptomyces isolates (n=31) into 14 different taxa. The most common
      streptomycetes were the mesophilic S. albidoflavus and moderately thermophilic S.
      thermocarboxydus. The Nocardiopsis isolates (n=11) belonged to six different
      taxa, whereas the thermoactinomycetes were mainly members of the species
      Laceyella sacchari (formerly Thermoactinomyces sacchari). The results indicated
      the probable presence of one or more new species within each of these genera.
      Obviously, the drying stage used in the board making processes had eliminated all
      members of the species Streptomyces and Nocardiopsis present in the wet recycled
      fibre pulp samples. Only the thermotolerant endospores of L. sacchari were still
      present in the final products. The potential of automated ribotyping for
      identifying actinobacteria was indicated, as soon as comprehensive identification
      libraries became available.

PMID- 16292556
TI  - Identification and disruptional analysis of the Streptomyces cinnamonensis msdA
      gene, encoding methylmalonic acid semialdehyde dehydrogenase.
AB  - The msdA gene encodes methylmalonic acid semialdehyde dehydrogenase (MSDH) and is
      known to be involved in valine catabolism in Streptomyces coelicolor. Using
      degenerative primers, a homolog of msdA gene was cloned and sequenced from the
      monensin producer, Streptomyces cinnamonensis. RT-PCR results showed msdA was
      expressed in a vegetative culture, bump-seed culture and the early stages of oil
      based monensin fermentation. However, isotopic labeling of monensin A by [2, 4
      (13)C(2)]butyrate revealed that this MSDH does not play a role in providing
      precursors such as methylmalonyl-CoA for the monensin biosynthesis under these
      fermentation conditions. Using a PCR-targeting method, msdA was disrupted by
      insertion of an apramycin resistance gene in S. cinnamonensis C730.1.
      Fermentation results revealed that the resulting DeltamsdA mutant (CXL1.1)
      produced comparable levels of monensin to that observed for C730.1. This result
      is consistent with the hypothesis that butyrate metabolism in S. cinnamonensis in
      the oil-based fermentation is not mediated by msdA, and that methylmalonyl-CoA is
      probably produced through direct oxidation of the pro-S methyl group of
      isobutyryl-CoA. The CXL1.1 mutant and C730.1 were both able to grow in minimal
      medium with valine or butyrate as the sole carbon source, contrasting previous
      observations for S. coelicolor which demonstrated msdA is required for growth on
      valine. In conclusion, loss of the S. cinnamonensis msdA neither affects valine
      catabolism in a minimal medium, nor butyrate metabolism in an oil-based medium,
      and its role remains an enigma.

PMID- 16292557
TI  - The effects of organic carbon, ammoniacal-nitrogen, and oxygen partial pressure
      on the stratification of membrane-aerated biofilms.
AB  - The purpose of this study was to examine the effects of different nutrient
      (carbon, nitrogen, oxygen) concentrations on the microbial activity and community
      structure in membrane-aerated biofilms (MABs). MABs were grown under well-defined
      conditions of fluid flow, substrate concentration, and membrane oxygen partial
      pressure. Biofilms were then removed and thin-sliced using a cryostat/microtome
      parallel to the membrane. Individual slices were analyzed for changes with depth
      in biomass density, respiratory activity, and the population densities of ammonia
      oxidizing and denitrifying bacteria populations. Oxygen-sensing microelectrodes
      were used to determine the depth of oxygen penetration into each biofilm. Our
      results demonstrated that ammonia-oxidizing bacteria grow near the membrane,
      while denitrifying bacteria grow a substantial distance from the membrane.
      However, nitrifying and denitrifying bacteria did not grow simultaneously when
      organic concentrations became too high or ammonia concentrations became too low.
      In conclusion, membrane-aerated biofilms exhibit substantial stratification with
      respect to community structure and activity. A fundamental understanding of the
      factors that control this stratification will help optimize the performance of
      full-scale membrane-aerated biofilm reactors for wastewater treatment.

PMID- 16292558
TI  - Controlled formation of volatile components in cider making using a combination
      of Saccharomyces cerevisiae and Hanseniaspora valbyensis yeast species.
AB  - The effect of pure and mixed fermentation by Saccharomyces cerevisiae and
      Hanseniaspora valbyensis on the formation of major volatile components in cider
      was investigated. When the interaction between yeast strains of S. cerevisiae and
      H. valbyensis was studied, it was found that the two strains each affected the
      cell growth of the other upon inoculation of S. cerevisiae during growth of H.
      valbyensis. The effects of pure and mixed cultures of S. cerevisiae and H.
      valbyensis on alcohol fermentation and major volatile compound formation in cider
      were assessed. S. cerevisiae showed a conversion of sugar to alcohol of 11.5%,
      while H. valbyensis produced alcohol with a conversion not exceeding 6%. Higher
      concentrations of ethyl acetate and phenethyl acetate were obtained with H.
      valbyensis, and higher concentrations of isoamyl alcohol and isobutyl were formed
      by S. cerevisiae. Consequently, a combination of these two yeast species in
      sequential fermentation was used to increase the concentration of ethyl esters by
      7.41-20.96%, and to decrease the alcohol concentration by 25.06-51.38%. Efficient
      control of the formation of volatile compounds was achieved by adjusting the
      inoculation time of the two yeasts.

PMID- 16292559
TI  - Cyclic AMP-specific and cyclic GMP-specific phosphodiesterase isoenzymes in human
      cavernous arteries--immunohistochemical distribution and functional significance.
AB  - OBJECTIVES: It has been well established that male erectile dysfunction is
      frequently associated with vascular diseases. The normal function of cavernous
      arteries is considered a prerequisite to maintain sufficient blood flow to the
      trabecular spaces in order to enable penile erection. Contractility of cavernous
      arteries is regulated by the peripheral autonomic nervous system and endogenous
      factors released from the endothelial cell layer. A significant increase of blood
      flow in the central cavernous arteries is the initial event leading to penile
      tumescence and rigidity. Besides the significance of the nitric oxide/cyclic
      guanosine monophosphate (cGMP)-mediated mechanisms, the cyclic AMP (cAMP)
      signalling pathway is also involved in the regulation of tone of the erectile
      tissue, and interactions between cGMP- and cAMP-mediated mechanisms have been
      demonstrated. The aim of the present study was to investigate by means of
      immunohistochemistry the presence of the phosphodiesterase (PDE) isoenzymes 3, 4
      (cAMP-specific PDEs) and 5 (cGMP-specific PDE) in thin sections of human central
      cavernous arteries (HCA) and their functional significance in the mechanism of
      vessel tone regulation. METHODS: Functional experiments were performed using
      circular segments of HCA and strip preparations of the human corpus cavernosum
      (HCC). Relaxant effects induced by the cumulative addition of the PDE inhibitors
      milrinone (PDE3 inhibitor), rolipram (PDE4 inhibitor) and sildenafil (PDE5
      inhibitor; 0.01, 0.1, 1 and 10 M) were studied in preparations of HCA and HCC
      challenged by 1 M norepinephrine (NE). Moreover, immunohistochemistry was carried
      out in order to evaluate the expression of PDE3, PDE4 and PDE5 in thin sections
      of HCA. RESULTS: Milrinone, rolipram and sildenafil dose-dependently reversed the
      NE-induced tension of the isolated vascular segments and HCC strips with
      sildenafil being the most effective drug. Neither rolipram nor milrinone reached
      an EC50 value. Abundant immunoreactivities specific for PDE3, PDE4 and PDE5 were
      observed in the entire smooth musculature of the wall of HCA and resistance
      arteries. In addition, immunoreactivity for PDE4 was also detected in the
      cytoplasm of endothelial cells lining the cavernous arteries. CONCLUSIONS: The
      cGMP-dependent relaxation of cavernous arteries is not only dependent on the
      normal function of the peripheral autonomic nervous system but also on the
      functional integrity of the vascular endothelium. The expression of the cGMP
      specific PDE5 and the ability of the PDE5 inhibitor sildenafil to reverse the
      adrenergic tension of isolated segments of HCA underline the important role of
      the NO/cGMP pathway in the control of smooth muscle tone of human trabecular
      smooth musculature and penile cavernous arteries. Our results also suggest a
      significance of the cAMP-dependent signaling mechanisms in the regulation of
      tension of central HCAs. The present findings are also in support of the
      hypothesis of interactions between the cGMP- and cAMP-mediated signaling pathways
      in HCAs. Further investigations are indicated in order to outline potential
      differences between central HCAs and helicine resistance arteries. This may help
      to understand better the relations between structural and functional changes in
      the penile erectile tissue in patients with cardiovascular diseases and
      endothelial dysfunction.

PMID- 16292560
TI  - The HOXC13-controlled expression of early hair keratin genes in the human hair
      follicle does not involve TALE proteins MEIS and PREP as cofactors.
AB  - We previously showed that the homeodomain protein HOXC13 is involved in the
      expression control of the early human hair keratin genes hHa5 and hHa2, which
      contain specific HOXC13 binding sites in their proximal promoters. Hox
      specificity is generally thought to be enhanced by the interaction with members
      of the TALE superclass of homeodomain proteins Pbx, Meis, and Prep. Using reverse
      transcription PCR with total human hair follicle RNA, we demonstrated transcripts
      of the major TALE proteins PBX1-4, MEIS1, 2 and PREP1, 2 in the human hair
      follicle. In view of the presence of MEIS/PREP responsive elements in close
      vicinity to the HOXC13 binding sites of the hHa5 and hHa2 promoters, we
      determined the expression sites of these TALE proteins in the human hair
      follicle. We found that MEIS1, MEIS2, PREP1 and PREP2 were differentially
      expressed in the three layers of the inner root sheath. In addition, MEIS2 and
      PREP1 exhibited expression in the mid-to upper hair cortex, with PREP1 being also
      expressed in the dermal papilla and the connective tissue sheath of the hair
      follicle. In virtually all cases, the expression of these TALE proteins was
      exclusively cytoplasmic. Considering that in contrast, HOXC13 is expressed in the
      nuclei of matrix, precortex and lower cuticle cells of the hair follicle, our
      data suggest that despite the presence of MEIS/PREP binding sites in the hHa5 and
      hHa2 promoters, the HOXC13-controlled activation of these genes in the hair
      follicle does not seem to involve these TALE proteins as cofactors.

PMID- 16292561
TI  - A model for the mechanism of generating the auditory evoked field.
AB  - The auditory evoked potentials and fields, recorded with electro- and magneto
      encephalography, respectively, have the prominent peak at the latency of about
      100 ms, named N100(m). The mechanism for generating the peak is not yet fully
      elucidated, however. Firstly, this study reviewed empirical results on the
      mechanism that had been previously published by the same author. The results
      showed that phases of the ongoing oscillations at around 6 Hz above the auditory
      cortex are locked with respect to onsets of the auditory stimuli during the
      period of N100 m, and also that powers of the oscillations are increased during
      the same period. Taking into account these results as well as another evidence
      that the peak arises from multiple sources within the auditory cortex, a model
      for the mechanism of generating the auditory N100 m was proposed. The model
      assumed several oscillators in the auditory cortex, whose phases were locked
      during the period of N100 m, but not locked at other periods. Computer simulation
      validated the model. The model could represent a starting point for further
      experiment and simulation.

PMID- 16292562
TI  - Vitellogenin detection in Caiman latirostris (Crocodylia: Alligatoridae): a tool
      to assess environmental estrogen exposure in wildlife.
AB  - Environmental pollution with endocrine disrupting compounds (EDCs) has adverse
      effects on the ecosystem's health. Caiman latirostris are widely distributed in
      South American aquatic ecosystems. Caimans have physiological and ecological
      characteristics that make them particularly vulnerable to EDCs exposure and
      suitable candidate as a sentinel species. Vitellogenin (Vtg) is a yolk pre-cursor
      protein synthesized by the liver of non-mammalian vertebrates and induced in
      response to estrogen. Purified plasma Vtg from caimans injected with estradiol
      17beta (E2) was used to generate a polyclonal anti-body. Anti-body specificity
      was assessed using Western blot. The antiserum was also effective in detecting
      turtle Vtg, exhibiting high cross-reactivity with Vtg from Phrynops hilarii and
      Trachemys scripta dorbigni. We developed a specific and highly sensitive ELISA
      for caiman Vtg. This method has a detection limit of 0.1 ng/ml of plasma. The
      ELISA did not detect Vtg in plasma of non-induced male caimans. Induction of Vtg
      in male caimans was evaluated in response to one or two (7 days apart) doses of
      E2. Due to its high sensitivity, ELISA allows to measure the small increases in
      plasma Vtg after exposure to exogenous estrogen. A priming effect was observed
      following the second E2 dose, with a tenfold increase in circulating Vtg. Hepatic
      synthesis was confirmed by immunohistochemistry. The results presented herein
      suggest that detection of plasma Vtg in male caimans might become a valuable tool
      in biomonitoring xenoestrogen exposure in a polluted environment.

PMID- 16292563
TI  - [Prophylactic gastric surgery].
AB  - A premalignant condition with high risk of gastric cancer is the basis for
      prophylactic gastric surgery. The germline mutation carrier in the E-cadherin
      gene has a lifetime risk of 70-80% for diffuse-type gastric cancer, and high
      grade intraepithelial neoplasia has a 60-70% gastric cancer risk. Other
      premalignant conditions such as HNPCC syndrome (5% gastric cancer) and low-grade
      intraepithelial neoplasia (10% risk) are moderate risk factors for developing
      gastric cancer. They do not justify prophylactic surgery, but surveillance is
      required. In case high-grade intraepithelial neoplasia or early gastric cancer is
      detected, an option is extended radicality with total gastrectomy instead of
      subtotal gastric resection. Positive family history and early-onset of gastric
      cancer are risk factors to consider when discussing prophylactic gastrectomy or
      extended radicality.

PMID- 16292564
TI  - [Prophylactic surgery for hereditary non-polyposis colorectal cancer].
AB  - The most frequent hereditary colorectal cancer predisposition is Lynch syndrome,
      or hereditary non-polyposis colorectal cancer. The option of prophylactic surgery
      relies on the penetrance of the genetic defect and the heterogeneity of the
      condition. Since 20% of all mutation carriers never move on to develop cancer,
      the purely prophylactic setting is not indicated. However, when colorectal cancer
      is diagnosed, the question arises if the patient may benefit from extended
      surgery -- total colectomy or (restorative) proctocolectomy. These patients
      should be entered into the ongoing prospective-randomized study by German Cancer
      Aid (http://www.hnpcc-studie.de). Due to substantially increased cancer risk and
      poor surveillance options, the endometrium and stomach are also subject to the
      question of prophylactic intervention.

PMID- 16292566
TI  - Antioxidant responses to enhanced generation of superoxide anion radical and
      hydrogen peroxide in the copper-stressed mulberry plants.
AB  - The aim of the study was to implicate the generation of reactive oxygen species
      (ROS) and altered cellular redox environment with the effects of Cu-deficiency or
      Cu-excess in mulberry (Morus alba L.) cv. Kanva 2 plants. A study of
      antioxidative responses, indicators of oxidative damage and cellular redox
      environment in Cu-deficient or Cu-excess mulberry plants was undertaken. While
      the young leaves of plants supplied with nil Cu showed chlorosis and necrotic
      scorching of laminae, the older and middle leaves of plants supplied with nil or
      0.1 microM Cu showed purplish-brown pigmented interveinal areas that later turned
      necrotic along the apices and margins of leaves. The Cu-excess plants showed
      accelerated senescence of the older leaves. The Cu-deficient plants showed
      accumulation of hydrogen peroxide and superoxide anion radical. The accumulation
      of hydrogen peroxide was strikingly intense in the middle portion of trichomes on
      Cu-deficient leaves. Though the concentration of total ascorbate increased with
      the increasing supply of Cu, the ratio of the redox couple (DHA/ascorbic acid)
      increased in Cu-deficient or Cu-excess plants. The activities of superoxide
      dismutase (EC 1.15.1.1), catalase (EC 1.11.1.6), peroxidase (EC 1.11.1.7),
      ascorbate peroxidase (EC 1.11.1.11) and glutathione reductase (EC 1.6.4.2)
      increased in both Cu-deficient and Cu-excess plants. The results suggest that
      deficiency of Cu aggravates oxidative stress through enhanced generation of ROS
      and disturbed redox couple. Excess of Cu damaged roots, accelerated the rate of
      senescence in the older leaves, induced antioxidant responses and disturbed the
      cellular redox environment in the young leaves of mulberry plants.

PMID- 16292565
TI  - Enhanced cold tolerance in transgenic tobacco expressing a chloroplast omega-3
      fatty acid desaturase gene under the control of a cold-inducible promoter.
AB  - A new cold-inducible genetic construct was cloned using a chloroplast-specific
      omega-3-fatty acid desaturase gene (FAD7) under the control of a cold-inducible
      promoter (cor15a) from Arabidopsis thaliana. RT-PCR confirmed a marked increase
      in FAD7 expression, in young Nicotiana tabacum (cv. Havana) plants harboring
      cor15a-FAD7, after a short-term exposure to cold. When young, cold-induced
      tobacco seedlings were exposed to low-temperature (0.5, 2 or 3.5 degrees C) for
      up to 44 days, survival within independent cor15a-FAD7 transgenic lines (40.2
      96%) was far superior to the wild type (6.7-10.2%). In addition, the major
      trienoic fatty acid species remained stable in cold-induced cor15a-FAD7 N.
      tabacum plants under prolonged cold storage while the levels of hexadecatrienoic
      acid (16:3) and octadecatrienoic acid (18:3) declined in wild type plants under
      the same conditions (79 and 20.7% respectively). Electron microscopy showed that
      chloroplast membrane ultrastructure in cor15a-FAD7 transgenic plants was
      unaffected by prolonged exposure to cold temperatures. In contrast, wild type
      plants experienced a loss of granal stacking and disorganization of the thylakoid
      membrane under the same conditions. Changes in membrane integrity coincided with
      a precipitous decline in leaf chlorophyll concentration and low survival rates in
      wild type plants. Cold-induced double transgenic N. alata (cv. Domino Mix)
      plants, harboring both the cor15a-FAD7 cold-tolerance gene and a cor15a-IPT dark
      tolerance gene, exhibited dramatically higher survival rates (89-90%) than wild
      type plants (2%) under prolonged cold storage under dark conditions (2 degrees C
      for 50 days).

PMID- 16292568
TI  - Identification of expression profiles of sorghum genes in response to greenbug
      phloem-feeding using cDNA subtraction and microarray analysis.
AB  - The phloem-feeding by greenbug (Schizaphis graminum) elicits unique interactions
      with their host plants. To investigate the expression profiles of sorghum genes
      responsive to greenbug feeding, two subtractive cDNA libraries were constructed
      through different combinatorial subtractions in a strong greenbug resistance
      sorghum M627 line and a susceptible Tx7000 line with or without greenbug
      infestation. A total of 3,508 cDNAs were selected from the two cDNA libraries,
      and subsequent cDNA microarray and northern blot analyses were performed for
      identification of sorghum genes responsive to greenbugs. In total, 157 sorghum
      transcripts were identified to be differentially expressed by greenbug feeding.
      The greenbug responsive genes were isolated and classified into nine categories
      according to the functional roles in plant metabolic pathways, such as defense,
      signal transduction, cell wall fortification, oxidative burst/stress,
      photosynthesis, development, cell maintenance, abiotic stress, and unknown
      function. Overall, the profiles of sorghum genes, responsive to greenbug phloem
      feeding shared common identities with other expression profiles known to be
      elicited by diverse stresses, including pathogenesis, abiotic stress, and
      wounding. In addition to well-known defense related regulators such as salicylic
      acid, jasmonic acid, and abscisic acid, auxin and gibberellic acid were also
      involved in mediation of the defense responses against greenbug phloem-feeding in
      sorghum.

PMID- 16292567
TI  - Presence of 'PSI free' LHCI and monomeric LHCII and subsequent effects on
      fluorescence characteristics in lincomycin treated maize.
AB  - The cause of the strong non-photochemical fluorescence quenching was examined in
      maize (Zea mays L.) plants that were treated with lincomycin during the 72 h
      period of greening. They were deficient in core complexes but seemed to contain
      the full complement of antennae. The following results were obtained: (1) High
      F(o) could not be attributed to the dark reduction of Q(A) but to the presence of
      a high amount of not properly organized antenna complexes due to the inhibited
      synthesis of reaction centres. (2) On illumination fluorescence intensity dropped
      considerably below F(o) within 20 s, and reached a steady state still below F(o).
      (3) Slowly relaxing part of non-photochemical quenching was significantly higher
      than in control plants. (4) De-epoxidation state was constant, and corresponded
      to the maximal value of the control. (5) Free Lhca1/4 dimers could be detected in
      all submembrane fractions, including the grana, obtained by digitonin
      fractionation. (6) Increase in the 679 and 700 nm fluorescence emissions could be
      attributed to the monomerisation of part of LHCII and to the presence of free
      Lhca2 or LHCII aggregates, respectively. (7) LHCII or PSII+LHCII and Lhca1/4
      interaction may contribute to the increase of long-wavelength fluorescence in the
      granal fraction. We assume that the elevated fluorescence quenching of monomeric
      LHCII as well as the interaction between LHCII or PSII+LHCII and Lhca1/4 can be
      considered as an explanation for the extensive non-photochemical fluorescence
      quenching in lincomycin treated plants. The permanent presence of zeaxanthin may
      have contributed to the fast formation of quenching.

PMID- 16292569
TI  - Phytotoxic, clastogenic and bioaccumulation effects of the environmental
      endocrine disruptor bisphenol A in various crops grown hydroponically.
AB  - The effects of the endocrine disruptor bisphenol A (BPA) at concentrations of 10
      and 50 mg l(-1) were evaluated on the germination and morphology, micronuclei
      (MN) content in root tip cells and BPA bioaccumulation of hydroponic seedlings of
      broad bean (Vicia faba L.), tomato (Lycopersicon esculentum Mill.), durum wheat
      (Triticum durum Desf.) and lettuce (Lactuca sativa L.) after 6 and 21 days of
      growth. In general, BPA at any dose used did not inhibit germination and early
      growth (6 days) of seedlings of the species examined, with the exception of
      primary root length of tomato which decreased at the higher BPA dose. In
      contrast, an evident phytotoxicity was induced by BPA in all species after 21
      days of growth with evident morphological anomalies and significant reductions of
      the lengths and fresh and dry weights of shoots and roots of seedlings. With
      respect to the nutrient medium without seedlings, BPA concentration decreased
      markedly during the growth period in the presence of broad bean and tomato
      seedlings, and limitedly in the presence of durum wheat and, especially, lettuce.
      Further, the presence of BPA measured in roots and shoots of broad bean and
      tomato after 21-day growth indicated that bioaccumulation of BPA had occurred.
      The number of MN in broad bean and durum wheat root tip cells increased markedly
      by treatment with BPA at both concentrations, thus suggesting a potential
      clastogenic activity of BPA in these species.

PMID- 16292570
TI  - Effect of carbon and nitrogen sources, pH and temperature on in vitro culture of
      several isolates of Amanita caesarea (Scop.:Fr.) Pers.
AB  - Several isolates were obtained from sporocarps of Amanita caesarea (Scop.: Fr.)
      Pers. associated with Quercus suber and Castanea sativa coming from the southwest
      of Spain. Culture conditions were optimized for these isolates. The largest
      radial growth was obtained at pH 6-7, and optimal growth temperature was 24-28
      degrees C depending on the isolate. Albumin bovine and nitrate produced the
      largest patch size diameters, but the greatest mycelium dry weight yields were
      obtained with ammonium. Mannitol produced the largest radial growth, and mannitol
      and glucose yielded the biggest mycelium dry weights. Although variations in
      growth behaviour between isolates were observed, only one internal spacer
      sequence-restriction fragment length polymorphism type was obtained.

PMID- 16292571
TI  - Path integration: is there a difference between athletes and non-athletes?
AB  - The ability to estimate distance walked when blindfolded is associated with the
      vestibular, proprioceptive and (loco-)motor systems. In this study, we examined
      subjects' ability to walk when blindfolded to a previously seen target. We
      examined whether there is a difference of performance in path integration between
      athletes and non-athletes. Two groups of healthy volunteers took part in this
      experiment: 21 athletes and 20 non-athletes. Subjects were asked to walk at three
      different velocities (slow, normal, fast) to a target (10 m in front of them)
      that they had seen before being blindfolded. Increase in velocity was associated
      with a decrease in the distance walked for both groups. Both groups were accurate
      at normal velocities. Athletes were also accurate at fast velocities whereas non
      athletes undershot the target. In both groups, accuracy considerably decreased at
      slow velocities. It seems that our perceptual system can adapt to different
      velocities (normal, fast) but is most strongly disrupted at low velocity. When
      attempting to modify walking velocity, step length is also modified, playing a
      determining role in the estimation of distance.

PMID- 16292572
TI  - Thiopental sodium reduces glutamate extracellular levels in rat intact prefrontal
      cortex.
AB  - To investigate the effect of thiopental sodium on glutamate extracellular levels
      in the prefrontal cortex (PFC) of rats, a microdialysis probe was inserted into
      the PFC, the perfusate was collected every 10 min throughout the experiment with
      thiopental sodium ip or perfused into the PFC locally. The concentrations of
      glutamate in the perfusate were determined by reversed-phase high performance
      liquid chromatography. Thiopental sodium 30 mg kg(-1) ip significantly decreased
      glutamate levels in the perfusate after 10, 20, 30, and 40 min; glutamate levels
      in the perfusate were also decreased from 10 to 90 min after thiopental sodium 50
      mg kg(-1) ip. Thiopental sodium with concentrations of 30, 100, or 300 microM
      perfused into the PFC also decreased glutamate levels in the perfusate
      significantly. The results suggest that thiopental sodium decreases glutamate
      extracellular levels in rat intact PFC.

PMID- 16292573
TI  - Differential exploitation of the inertia tensor in multi-joint arm reaching.
AB  - The identification of the kinaesthetic information used for directing 3D multi
      joint arm movements toward a target remains an open question. Several
      psychophysical studies have suggested that the ability to perceive and control
      the spatial orientation of our limbs depends on the exploitation of the
      eigenvectors (e (3)) of the inertia tensor (I ( ij )), which correspond to the
      arm rotational inertial axes. The present experiment aimed at investigating
      whether e (3) was used as a collective variable to direct the masses toward the
      target and hence to control the spatial accuracy of the final hand position.
      Natural, unconstrained, three-dimensional multi-joint reaching movements were
      submitted to alterations of forearm mass distribution. Given the existence of
      several "sensorimotor strategies" for the control of arm movements, the
      participants were a priori contrasted and ranged in groups according to their
      reliance on either visual or kinaesthetic information. The results indicated (1)
      the dependency of the arm's directional control on I ( ij ) parameters, (2) a non
      linear relationship between the performance predicted by the inertia tensor and
      the observed performance, depending on the deviation amplitude and (3) the
      presence of a large inter-individual variability suggesting the existence of
      different strategies, including proprioceptive compensation mechanisms. This
      study validates in unconstrained multi-joint arm movements the exploitation of
      the inertia tensor by the central nervous system, thus simplifying the
      coordination of the segments' masses during reaching. The results also provide
      evidence for the existence of motor alternatives in exploiting proprioceptive
      information that may depend on spatial referencing modes.

PMID- 16292574
TI  - Temporal characteristics of neurons in the central mesencephalic reticular
      formation of head unrestrained monkeys.
AB  - The accompanying paper demonstrated two distinct types of central mesencephalic
      reticular formation (cMRF) neuron that discharged before or after the gaze
      movement: pre-saccadic or post-saccadic. The movement fields of pre-saccadic
      neurons were most closely associated with gaze displacement. The movement fields
      of post-saccadic neurons were most closely associated with head displacement.
      Here we examine the relationships of the discharge patterns of these cMRF neurons
      with the temporal aspects of gaze or head movement. For pre-saccadic cMRF neurons
      with monotonically open movement fields, we demonstrate that burst duration
      correlated closely with gaze duration. In addition, the peak discharge of the
      majority of pre-saccadic neurons was closely correlated with peak gaze velocity.
      In contrast, discharge parameters of post-saccadic neurons were best correlated
      with the time of peak head velocity. However, the duration and peak discharge of
      post-saccadic discharge was only weakly related to the duration and peak velocity
      of head movement. As a result, for the majority of post-saccadic neurons the
      discharge waveform poorly correlated with the dynamics of head movement. We
      suggest that the discharge characteristics of pre-saccadic cMRF neurons with
      monotonically open movement fields are similar to that of direction long-lead
      burst neurons found previously in the paramedian portion of the pontine reticular
      formation (PPRF; Hepp and Henn 1983). In light of their anatomic connections with
      the PPRF, these pre-saccadic neurons could form a parallel pathway that
      participates in the transformation from the spatial coding of gaze in the
      superior colliculus (SC) to the temporal coding displayed by excitatory burst
      neurons of the PPRF. In contrast, closed and non-monotonically open movement
      field pre-saccadic neurons could play a critical role in feedback to the SC. The
      current data do not support a role for post-saccadic cMRF neurons in the direct
      control of head movements, but suggest that they may serve a feedback or
      reafference function, providing a signal of current head amplitude to upstream
      regions involved in head control.

PMID- 16292576
TI  - Functional analysis through site-directed mutations and phylogeny of the Candida
      albicans LYS1-encoded saccharopine dehydrogenase.
AB  - Candida albicans LYS1-encoded saccharopine dehydrogenase (CaLys1p, SDH) catalyzes
      the final biosynthetic step (saccharopine to lysine + alpha-ketoglutarate) of the
      novel alpha-aminoadipate pathway for lysine synthesis in fungi. The reverse
      reaction catalyzed by lysine-alpha-ketoglutarate reductase (LKR) is used
      exclusively in animals and plants for the catabolism of excess lysine. The 1,146
      bp C. albicans LYS1 ORF encodes a 382 amino acid SDH. In the present
      investigation, we have used E. coli-expressed recombinant C. albicans Lys1p for
      the determination of both forward and reverse SDH activities in vitro, compared
      the sequence identity of C. albicans Lys1p with other known SDHs and LKRs,
      performed extensive site-directed mutational analyses of conserved amino acid
      residues and analyzed the phylogenetic relationship of C. albicans Lys1p to other
      known SDHs and LKRs. We have identified 14 of the 68 amino acid substitutions as
      essential for C. albicans Lys1p SDH activity, including two highly conserved
      functional motifs, H93XXF96XH98 and G138XXXG142XXG145. These results provided new
      insight into the functional and phylogenetic characteristics of the distinct
      biosynthetic SDH in fungi and catabolic LKR in higher eukaryotes.

PMID- 16292575
TI  - Spatial characteristics of neurons in the central mesencephalic reticular
      formation (cMRF) of head-unrestrained monkeys.
AB  - Prior studies of the central portion of the mesencephalic reticular formation
      (cMRF) have shown that in head-restrained monkeys, neurons discharge prior to
      saccades. Here, we provide a systematic analysis of the patterns of activity in
      cMRF neurons during head unrestrained gaze shifts. Two types of cMRF neurons were
      found: presaccadic neurons began to discharge before the onset of gaze movements,
      while postsaccadic neurons began to discharge after gaze shift onset and
      typically after the end of the gaze shift. Presaccadic neuronal responses were
      well correlated with gaze movements, while the discharge of postsaccadic neurons
      was more closely associated with head movements. The activity of presaccadic
      neurons was organized into gaze movement fields, while the activity of
      postsaccadic neurons was better organized into movement fields associated with
      head displacement. We found that cMRF neurons displayed both open and closed
      movement field responses. Neurons with closed movement fields discharged before a
      specific set of gaze (presaccadic) or head (postsaccadic) movement amplitudes and
      directions and had a clear distal boundary. Neurons with open movement fields
      discharged for gaze or head movements of a specific direction and also for
      movement amplitudes up to the limit of measurement (70 degrees). A subset of open
      movement field neurons displayed an increased discharge with increased gaze shift
      amplitudes, similar to pontine burst neurons, and were called monotonically
      increasing open movement field neurons. In contrast, neurons with non
      monotonically open movement fields demonstrated activity for all gaze shift
      amplitudes, but their activity reached a plateau or declined gradually for gaze
      shifts beyond specific amplitudes. We suggest that presaccadic neurons with open
      movement fields participate in a descending pathway providing gaze signals to
      medium-lead burst neurons in the paramedian pontine reticular formation, while
      presaccadic closed movement field neurons may participate in feedback to the
      superior colliculus. The previously unrecognized group of postsaccadic cMRF
      neurons may provide signals of head position or velocity to the thalamus,
      cerebellum, or spinal cord.

PMID- 16292578
TI  - Analysis of plasma elastase levels in early and late onset preeclampsia.
AB  - BACKGROUND: Circulatory neutrophils have been reported to be activated in
      preeclampsia. It has been suggested that maternal plasma levels of elastase may
      serve as a possible cell-free marker to quantify such activation. Although plasma
      elastase levels have been found to be elevated in cases with manifest
      preeclampsia and eclampsia, this has not yet been examined in cases with early
      and late onset preeclampsia. We have now examined this aspect. METHODS: In this
      retrospective study, maternal plasma samples were examined from eight cases with
      early onset preeclampsia (<34 weeks of gestation), eight cases with late onset
      preeclampsia (>34 weeks of gestation) and an equal number of gestational age
      matched normotensive term controls. Plasma concentrations of elastase were
      measured by ELISA using a commercially available assay. RESULTS: Plasma elastase
      concentrations were significantly elevated the preeclampsia study group when
      compared to the normotensive control group (median=139.2 ng/ml versus median=72.1
      ng/ml; P=0.0025). These elevations remained significant when the preeclampsia
      study group was stratified into case with early onset preeclampsia (median=118.8
      ng/ml versus median=62.2 ng/ml; P=0.03), but jailed failed to attain significance
      for those cases with late onset preeclampsia (median=181.3 ng/ml versus
      median=86.3 ng/ml; P=0.061). CONCLUSIONS: Our data indicate that elastase levels
      are elevated in both early and late onset forms of preeclampsia, and imply that
      the activation of neutrophils may be more acute in the former than in the latter
      (238 words).

PMID- 16292577
TI  - Roles of PACAP and PHI as inhibitory neurotransmitters in the circular muscle of
      mouse antrum.
AB  - Mediators of neurogenic responses of the gastric antrum were studied in wild-type
      and pituitary adenylate cyclase-activating polypeptide (PACAP) -knockout (KO)
      mice. Electrical field stimulation (EFS) to the circular muscle strips of the
      wild-type mouse antrum induced a triphasic response; rapid transient relaxation
      and contraction, and sustained relaxation that was prolonged for an extended
      period after the end of EFS. The transient relaxation and contraction were
      completely inhibited by L-nitroarginine and atropine, respectively. The sustained
      relaxation was significantly inhibited by a PACAP receptor antagonist, PACAP(6
      38). The antral strips prepared from PACAP-KO mice unexpectedly exhibited a tri
      phasic response. However, the sustained relaxation was decreased to about one
      half of that observed in wild-type mice. PACAP(6-38) inhibited EFS-induced
      sustained relaxation (33.5% of control) in PACAP-KO mice. Anti-peptide histidine
      isoleucine (PHI) serum partially (the 30% inhibition) or significantly (the 60%
      inhibition) inhibited the sustained relaxations in the wild-type and PACAP-KO
      mice, respectively. The immunoreactivities to the anti-PACAP and anti-PHI serums
      were found in myenteric ganglia of the mouse antrum. These results suggest that
      nitric oxide and acetylcholine mediate the transient relaxation and contraction,
      respectively, and that PACAP and PHI separately mediate the sustained relaxation
      in the antrum of the mouse stomach.

PMID- 16292579
TI  - Relation between plasma adenosine and serum TSH levels in women with hyperemesis
      gravidarum.
AB  - INTRODUCTION: This study investigated the relation between adenosine and thyroid
      function associated with hyperemesis gravidarum. METHODS: We examined 84 Japanese
      singleton pregnant women with an average age of 33.0+/-5.8 years at 9-12 weeks
      gestation being managed at our hospital. The patients were divided into three
      groups according to the severity of emesis: (1) those with hyperemesis gravidarum
      (nausea and vomiting with weight loss >5%, n=13), (2) those with emesis (nausea
      and vomiting with weight loss <5%, n=31), and (3) those with no symptoms as a
      control (n=40). RESULTS: The average serum TSH levels in the emesis and
      hyperemesis groups were significantly higher than that in the control group
      (P<0.05). The average plasma adenosine level in the hyperemesis group was
      significantly higher than those in the control pregnant and emesis groups
      (P<0.05). There were no significant differences in plasma adenosine levels
      between the control pregnant and emesis groups. The serum TSH level showed
      significant correlations with weight loss (%) and plasma adenosine levels
      (P<0.05). CONCLUSIONS: Our findings support the possible role of adenosine in
      counteracting the further progression of hyperemesis gravidarum associated with
      gestational thyrotoxicosis.

PMID- 16292580
TI  - The effect of exogenous spatial attention on auditory information processing.
AB  - This study investigated the effect of exogenous spatial attention on auditory
      information processing. In Experiments 1, 2 and 3, temporal order judgment tasks
      were performed to examine the effect. In Experiment 1 and 2, a cue tone was
      presented to either the left or right ear, followed by sequential presentation of
      two target tones. The subjects judged the order of presentation of the target
      tones. The results showed that subjects heard both tones simultaneously when the
      target tone, which was presented on the same side as the cue tone, was presented
      after the target tone on the opposite side. This indicates that spatial exogenous
      attention was aroused by the cue tone, and facilitated subsequent auditory
      information processing. Experiment 3 examined whether both cue position and
      frequency influence the resulting information processing. The same effect of
      spatial attention was observed, but the effect of attention to a certain
      frequency was only partially observed. In Experiment 4, a tone fusion judgment
      task was performed to examine whether the effect of spatial attention occurred in
      the initial stages of hearing. The result suggests that the effect occurred in
      the later stages of hearing.

PMID- 16292581
TI  - (99m)Tc-tetrofosmin as a prognostic agent?

PMID- 16292582
TI  - [Health surveys in Europe. Overview and activities to harmonize the methods and
      instruments for comparing the data].
AB  - In almost every European country health surveys are conducted in order to
      describe the health status of the population and to use these data for planning
      health services and preventive activities. In the last 10-15 years the
      availability and quality of data from population-based health surveys in Europe
      have greatly improved, particularly in the countries of Central and Eastern
      Europe. Nevertheless the design, quality of data and the comparability across
      countries, nations and cultures remain a challenge. Therefore WHO and EU have
      started various activities to harmonize the methods and instruments in health
      surveys. These activities are described in this contribution.

PMID- 16292583
TI  - Eosinophilic cellulitis or Wells' syndrome in a 6-year-old child.

PMID- 16292584
TI  - Pyridoxamine lowers oxalate excretion and kidney crystals in experimental
      hyperoxaluria: a potential therapy for primary hyperoxaluria.
AB  - In order to prevent kidney stones and nephrolithiasis in hyperoxaluria, a new
      treatment that specifically reduces oxalate production and therefore urinary
      oxalate excretion would be extremely valuable. Pyridoxamine(PM) could react with
      the carbonyl intermediates of oxalate biosynthesis, glycolaldehyde and
      glyoxylate, and prevent their metabolism to oxalate. In PM treated rats,
      endogenous urinary oxalate levels were consistently lower and became
      statistically different from controls after 12 days of experiment. In ethylene
      glycol-induced hyperoxaluria, PM treatment resulted in significantly lower (by
      ~50%) levels of urinary glycolate and oxalate excretion compared to untreated
      hyperoxaluric animals, as well as in a significant reduction in calcium oxalate
      crystal formation in papillary and medullary areas of the kidney. These results,
      coupled with favorable toxicity profiles of PM in humans, show promise for the
      therapeutic use of PM in primary hyperoxaluria and other kidney stone diseases.

PMID- 16292586
TI  - Sudden cardiac death during anabolic steroid abuse: morphologic and toxicologic
      findings in two fatal cases of bodybuilders.
AB  - We report two cases of sudden cardiac death (SCD) involving previously healthy
      bodybuilders who were chronic androgenic-anabolic steroids users. In both
      instances, autopsies, histology of the organs, and toxicologic screening were
      performed. Our findings support an emerging consensus that the effects of
      vigorous weight training, combined with anabolic steroid use and increased
      androgen sensitivity, may predispose these young men to myocardial injury and
      even SCD.

PMID- 16292585
TI  - Hyperoxaluria-induced oxidative stress and antioxidants for renal protection.
AB  - Renal cellular exposure to oxalate (Ox) and/or CaOx crystals leads to the
      production of reactive oxygen species (ROS), development of oxidative stress
      followed by injury and inflammation. Renal injury and inflammation appear to play
      a significant role in stone formation. ROS are produced from many sources and
      involve a variety of signaling pathways. Tissue culture and animal model studies
      show that treatments with anti-oxidants and free radical scavengers reduce
      Ox/CaOx crystal induced injuries. In addition, CaOx crystal deposition in kidneys
      is significantly reduced by treatments with antioxidants and free radical
      scavengers, indicating their efficacy. These results point towards a great
      potential for the therapeutic application of antioxidants and free radical
      scavengers to reduce stone recurrence particularly after shock wave lithotripsy,
      which is itself known to generate ROS and cause renal damage.

PMID- 16292587
TI  - Development of a tissue-engineered composite implant for treating traumatic
      paraplegia in rats.
AB  - This study was designed to assess a new composite implant to induce regeneration
      of injured spinal cord in paraplegic rats following complete cord transection.
      Neuronal xenogeneic cells from biopsies of adult nasal olfactory mucosa (NOM) of
      human origin, or spinal cords of human embryos, were cultured in two consecutive
      stages: stationary cultures in a viscous semi-solid gel (NVR-N-Gel) and in
      suspension on positively charged microcarriers (MCs). A tissue-engineered tubular
      scaffold, containing bundles of parallel nanofibers, was developed. Both the tube
      and the nanofibers were made of a biodegradable dextran sulphate-gelatin co
      precipitate. The suturable scaffold anchored the implant at the site of injury
      and provided guidance for the regenerating axons. Implants of adult human NOM
      cells were implanted into eight rats, from which a 4 mm segment of the spinal
      cord had been completely removed. Another four rats whose spinal cords had also
      been transected were implanted with a composite implant of cultured human
      embryonic spinal cord cells. Eight other cord-transected rats served as a control
      group. Physiological and behavioral analysis, performed 3 months after
      implantation, revealed partial recovery of function in one or two limbs in three
      out of eight animals of the NOM implanted group and in all the four rats that
      were implanted with cultured human embryonic spinal cord cells. Animals of the
      control group remained completely paralyzed and did not show transmission of
      stimuli to the brain. The utilization of an innovative composite implant to
      bridge a gap resulting from the transection and removal of a 4 mm spinal cord
      segment shows promise, suggesting the feasibility of this approach for partial
      reconstruction of spinal cord lesions. Such an implant may serve as a vital
      bridging station in acute and chronic cases of paraplegia.

PMID- 16292588
TI  - Bioresorbable polymers: heading for a new generation of spinal cages.
AB  - The use of polymer-based bioresorbable materials is now expanding to the realm of
      spinal interbody fusion. Bioresorbable polymers have important advantages over
      metals, because they are temporary, much less stiff, and radiolucent. Most
      promising is a group of alpha-polyesters, in particular polylactide acids (PLAs).
      Their biocompatibility is excellent, and they have sufficient stiffness and
      strength to provide initial and intermediate-term stability required for bone
      healing. However, polylactides have characteristics that make them vulnerable to
      complications if not properly controlled. Degradation rate strongly depends on
      polymer type, impurities, manufacturing process, sterilization, device size, and
      the local environment. The fact that larger implants degrade faster is contra
      intuitive, and should be considered in the design process. Also optimal surgical
      techniques, such as careful bone bed preparation, are required for a successful
      application of these materials. The purpose of this paper is to highlight the
      specific properties of these bioresorbable polymers and to discuss their
      potential and limitations. This is illustrated with early preclinical and
      clinical data.Bioresorbable cage technology is just emerging: their time
      engineered degradation characteristics allow controlled dynamization in interbody
      applications, facilitating spinal fusion. Their radiolucency improves image
      assessment of fusion healing. Acceptance and use of bioresorbable implants may
      increase as further research and clinical studies report on their safety,
      efficacy, and proper usage.

PMID- 16292589
TI  - Occupancy of dopamine D2 receptors by antipsychotic drugs is related to nicotine
      addiction in young patients with schizophrenia.
AB  - RATIONALE: Occupancy of dopamine D2 receptors by antipsychotic drugs depends on
      the individual availability of D2 receptors and on the dose and type of
      antipsychotic medication. It has been suggested that a low availability of these
      receptors may increase the risk for addictive behavior. OBJECTIVE: This study
      aims to show that patients with relatively high occupancy of D2 receptors by
      antipsychotic drugs are more prone to nicotine consumption. METHODS: Striatal D2
      receptor occupancy by equivalent doses of olanzapine or risperidone was assessed
      with [123I]iodobenzamide single-photon emission computed tomography (SPECT) in 36
      patients with schizophrenia. Smoking status at the time of SPECT imaging was
      assessed. The number of cigarettes used in the following three consecutive years
      was estimated with the Life Chart Schedule (LCS). RESULTS: There was a positive
      and significant relation between D2 receptor occupancy following treatment with
      olanzapine (n=19) or risperidone (n=12) and the number of cigarettes smoked in
      three consecutive years (r=0.60, p<0.001) in patients who smoked. There was a
      significant difference in the percentage of D2 occupancy for smokers (mean 74.3%,
      SD 12.8, n=31) and nonsmokers (mean 49.8%, SD 9.1, n=5). CONCLUSION: Frequency of
      cigarette smoking in schizophrenic patients treated with antipsychotic medication
      is significantly and negatively related to the availability of striatal D2
      receptors.

PMID- 16292591
TI  - Discriminative stimulus properties of tianeptine.
AB  - RATIONALE: In view of the difficulties in using antidepressant agents as training
      drugs in drug discrimination research, it was reasoned that tianeptine, because
      of its short duration of action and its lack of toxicity associated with long
      term administration, would be well-suited to establish a discriminative stimulus
      cue in rats and, hence, a valuable tool in the investigation of the neural basis
      of depression. OBJECTIVES: A drug discrimination procedure was used to determine
      whether tianeptine was associated with a specific discriminative stimulus effect,
      and substitution tests were conducted to determine whether this effect was
      mediated by serotonergic mechanisms. METHOD: Rats were trained to discriminate 10
      mg/kg tianeptine from saline and were tested with fluoxetine, a selective
      serotonin (5-HT) reuptake inhibitor; venlafaxine, a 5-HT/noradrenaline reuptake
      inhibitor; 8-hydroxy-(2-di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A
      agonist; and caffeine, a nonselective antagonist of adenosine receptors. RESULTS:
      Tianeptine induced a specific, robust, and sustained discriminative stimulus in
      rats. Fluoxetine and 8-OH-DPAT partially substituted for tianeptine by producing
      >50% of tianeptine-appropriate lever responding. In contrast, venlafaxine and
      caffeine induced responding on a saline-associated lever. CONCLUSION: The
      discriminative stimulus effect of tianeptine is mediated by serotonergic
      mechanisms, but what is surprising is that this mechanism seems to be, at least
      partially, enhanced by serotonergic transmission.

PMID- 16292592
TI  - Acute and subchronic effects of amitriptyline on processing capacity in
      neuropathic pain patients using visual event-related potentials: preliminary
      findings.
AB  - RATIONALE: Little is known about the effects of low doses of amitriptyline,
      prescribed in the treatment of neuropathic pain, on attentional processing
      capacity. OBJECTIVES: Changes due to amitriptyline treatment on attentional
      processing capacity were investigated on behavioral measures and event-related
      brain potentials (ERPs) in six patients with neuropathic pain. MATERIALS AND
      METHODS: Patients were treated for 15 consecutive days with 25 mg nocturnally
      administered amitriptyline or placebo in a double-blind crossover randomized
      design. Measurements were carried out on day 1 and day 15 of each treatment
      period. An attentional capacity probe task was used in which the difficulty level
      was manipulated, resulting in an easy and a hard condition, while task-irrelevant
      visual probes were presented. During task performance, ERPs were measured from
      the midline electrodes Fz, Cz, Pz, and Oz. RESULTS: Amitriptyline increased
      reaction times (RTs) after acute but not after subchronic administration. ERP
      analyses showed that P3 amplitudes to the task stimuli were not affected by
      amitriptyline in either treatment phase. Moreover, P3 amplitudes to the probes
      were increased in the easy compared to the hard task condition after subchronic
      amitriptyline treatment, indicating beneficial effects of repeated amitriptyline
      administration. In contrast, acute amitriptyline administration did reduce an
      earlier visual evoked potential, N1, preceding the P3 component. CONCLUSIONS: The
      results suggest that amitriptyline, even at low dosages of 25 mg, affects
      performance after acute administration in chronic neuropathic pain patients.
      After 2 weeks of treatment, performance appears to be unaffected. No deficits in
      processing capacity due to amitriptyline treatment were found.

PMID- 16292590
TI  - The mGluR5 antagonist MPEP selectively inhibits the onset and maintenance of
      ethanol self-administration in C57BL/6J mice.
AB  - RATIONALE: Many of the biochemical, physiological, and behavioral effects of
      ethanol are known to be mediated by ionotropic glutamate receptors. Emerging
      evidence implicates metabotropic glutamate receptors (mGluRs) in the
      biobehavioral effects of ethanol and other drugs of abuse, but there is little
      information regarding the role of mGluRs in the reinforcing effects of ethanol.
      MATERIALS AND METHODS: Male C57BL/6J mice were trained to lever-press on a
      concurrent fixed ratio 1 schedule of ethanol (10% v/v) vs water reinforcement
      during 16-h sessions. Effects of mGluR1, mGluR2/3, and mGluR5 antagonists were
      then tested on parameters of ethanol self-administration behavior. RESULTS: The
      mGluR5 antagonist MPEP (1-10 mg/kg, i.p.) dose-dependently reduced ethanol
      reinforced responding but had no effect on concurrent water-reinforced
      responding. Analysis of the temporal pattern of responding showed that MPEP
      reduced ethanol-reinforced responding during peak periods of behavior occurring
      during the early hours of the dark cycle. Further analysis showed that MPEP
      reduced the number of ethanol response bouts and bout-response rate. MPEP also
      produced a 13-fold delay in ethanol response onset (i.e., latency to the first
      response) with no corresponding effect on water response latency or locomotor
      activity. The mGluR1 antagonist CPCCOEt (1-10 mg/kg, i.p.) or the mGluR2/3
      antagonist LY 341495 (1-30 mg/kg, i.p.) failed to alter ethanol- or water
      reinforced responding. CONCLUSIONS: These data indicate that mGlu5 receptors
      selectively regulate the onset and maintenance of ethanol self-administration in
      a manner that is consistent with reduction in ethanol's reinforcement function.

PMID- 16292593
TI  - A comparison of drug-seeking behavior maintained by D-amphetamine, L-deprenyl
      (selegiline), and D-deprenyl under a second-order schedule in squirrel monkeys.
AB  - L-Deprenyl (selegiline) is used in the treatment of Parkinson's disease and has
      been proposed as an aid for cigarette smoking cessation and a treatment for
      psychostimulant abuse. L-Deprenyl is metabolized in the body to L-methamphetamine
      and L-amphetamine, suggesting that it may have abuse potential. The current study
      assessed whether L-deprenyl or its isomer would maintain drug-seeking behavior on
      a second-order schedule and whether L-deprenyl would alter drug-seeking behavior
      maintained by D-amphetamine if given as a pretreatment. Squirrel monkeys learned
      to respond on a second-order schedule of reinforcement, where every tenth
      response was followed by a brief light flash, and the first brief light flash
      after 30 min was paired with intravenous (i.v.) injection of D-amphetamine (0.56
      mg/kg), administered over a 2-min period at the end of the session. When
      responding was stable, saline or different i.v. doses of D-amphetamine (0.3-1.0
      mg/kg), L-deprenyl (0.1-10.0 mg/kg), and D-deprenyl (0.1-3.0 mg/kg) were
      substituted for 10 days each. Subsequently, monkeys were pretreated with 0.3 or
      1.0 mg/kg L-deprenyl intramuscularly 30 min prior to D-amphetamine baseline
      sessions. D-Amphetamine maintained high rates of drug-seeking behavior on the
      second-order schedule. D-Deprenyl maintained high rates of drug-seeking behavior
      similar to D-amphetamine. L-Deprenyl maintained lower rates of responding that
      were not significantly above saline substitution levels. Pretreatment with L
      deprenyl failed to alter drug-seeking behavior maintained by D-amphetamine. These
      results indicate that D-deprenyl, but not L-deprenyl, may have abuse potential.
      Under conditions where drug-seeking and drug-taking behaviors are actively
      maintained by D-amphetamine, L-deprenyl, at doses that specifically inhibit type
      B monoamine oxidase, may not be effective as a treatment.

PMID- 16292595
TI  - Nucleotide sequence of a new isolate of ribgrass mosaic tobamovirus infecting
      Impatiens New Guinea.
AB  - The complete nucleotide sequence of a tobamovirus isolated from Impatiens New
      Guinea was determined. The genome was 6302 nt long, and its genomic organisation
      was similar to those of other crucufer tobamoviruses. Sequence comparisons with
      the corresponding sequences of other crucifer tobamoviruses revealed highest
      levels of identity with the ribgrass mosaic virus (Shanghai isolate). A small
      open reading frame putatively encoding a 4.5-kDa protein with a low degree of
      similarity to the ORF6 of tobacco mosaic virus was found nested in the movement
      protein gene.

PMID- 16292597
TI  - A phylogenetic survey of recombination frequency in plant RNA viruses.
AB  - The severe economic consequences of emerging plant viruses highlights the
      importance of studies of plant virus evolution. One question of particular
      relevance is the extent to which the genomes of plant viruses are shaped by
      recombination. To this end we conducted a phylogenetic survey of recombination
      frequency in a wide range of positive-sense RNA plant viruses, utilizing 975
      capsid gene sequences and 157 complete genome sequences. In total, 12 of the 36
      RNA virus species analyzed showed evidence for recombination, comprising 17% of
      the capsid gene sequence alignments and 44% of the genome sequence alignments.
      Given the conservative nature of our analysis, we propose that recombination is a
      relatively common process in some plant RNA viruses, most notably the
      potyviruses.

PMID- 16292596
TI  - Immunization with influenza A NP-expressing vaccinia virus recombinant protects
      mice against experimental infection with human and avian influenza viruses.
AB  - Two-fold immunization of Balb/c mice with a vaccinia virus recombinant expressing
      the NP protein of influenza A/PR8/34 (H1N1) virus under the control of a strong
      synthetic promoter induced specific antibodies and protected animals against low
      dose challenge by mouse-adapted heterosubtypic variants of human A/Aichi2/68
      (H3N2) and avian A/Mallard/Pennsylvania/10218/84 (H5N2) influenza virus strains.
      The surviving immunized animals had lower anti-hemagglutinin antibody titers
      compared to non-immunized mice. There was no difference in viral titers in lungs
      of immunized and non-immunized animals that succumbed to the infection. In order
      to try to increase immune system presentation of NP-protein-derived peptides, and
      thereby increase their immunogenicity, we constructed another vaccinia-based NP
      expressing recombinant containing a rapid proteolysis signal covalently bound to
      the NP protein. This sequence, derived from the mouse ornithine decarboxylase
      gene has been shown to increase degradation of various proteins. However, we
      found that when used as part of a recombinant NP, this signal neither increased
      its proteolytic degradation, nor was it more efficient in the induction of a
      protective response against influenza infection.

PMID- 16292598
TI  - Daphne mosaic virus (DapMV), a new potyvirus from Daphne mezereum in the Czech
      Republic.
AB  - Daphne shrubs with light green rings and mosaic on leaves contained flexuous
      filamentous virions (696 x 13 nm) and cylindrical inclusions typical of the
      subdivision III of Edwardson's classification for inclusions induced by members
      of the family Potyviridae. Decoration tests using antisera to 67 potyviruses
      revealed distant serological relations among chilli veinal mottle virus,
      Colombian datura virus, papaya ringspot virus, tobacco vein mottling virus and
      yam mosaic virus. The 3' terminal region of the virus genome was amplified by RT
      PCR using primers specific for cloned and sequenced members of the family
      Potyviridae. The most similar sequences in the GenBank were those of isolates of
      wild potato mosaic virus (WPMV) and yam mild mosaic virus (YMMV), originating
      from Peru and Guadeloupe, respectively. The new sequence had 63.2% and 61.9%
      nucleotide identity to WPMV and YMMV in the coat protein gene. The results
      suggest that the Czech isolate from daphne should be regarded as a new member of
      the genus Potyvirus. The name daphne mosaic virus (DapMV) is suggested for this
      virus.

PMID- 16292599
TI  - Improved detection of grapevine leafroll-associated virus 1 by magnetic capture
      hybridisation RT-PCR on a conserved region of viral RNA.
AB  - We report the development of a sensitive diagnostic method for the detection of
      the grapevine leafroll-associated virus 1 (GLRaV-1). We have considered the
      current shortcoming in detection of GLRaV-1 to be linked to two factors, sequence
      variation in the viral RNA and low template concentration. Sequence information
      available allowed the selection of optimal target sequences for detection by RT
      PCR, having high copy number and low levels of sequence variation. This was
      combined with the use of magnetic capture hybridisation to allow the removal of
      RT-PCR inhibitors and the addition of 100-fold excess template RNA to a single RT
      PCR. The reproducibility of the technique was confirmed using field samples.

PMID- 16292601
TI  - Special issue: Homage to David Thomasma.

PMID- 16292600
TI  - Association analysis of estrogen receptor alpha gene polymorphisms with cross
      sectional geometry of the femoral neck in Caucasian nuclear families.
AB  - Bone geometry is a key factor in bone strength, which is the ultimate intrinsic
      determinant of fracture risk. Though the heritability of bone geometry is high,
      little effort has been spent on searching for the underlying genes. In this
      study, employing a sample of 1,873 subjects from 405 Caucasian nuclear families,
      we studied seven single nucleotide polymorphisms (SNPs) and their haplotypes of
      the ER-alpha gene for association with six hip geometric variables, namely, cross
      sectional area (CSA), cortical thickness (CT), endocortical diameter (ED),
      subperiosteal width (W), sectional modulus (Z) and buckling ratio (BR). The major
      method used was the quantitative transmission disequilibrium test (QTDT). Our
      major findings were summarized below. The within-family association between SNP4
      (rs1801132) in exon 4 with endocortical diameter and subperiosteal width was
      detected in single locus analyses (P=0.008 and 0.021, respectively) and verified
      in haplotype analyses (P=0.034 and 0.058, respectively). The total association of
      SNP4 with these two diameters was also observed in both single locus and
      haplotype analyses (P=0.005 and 0.031 for ED, plus P=0.003 and 0.070 for W). In
      addition, the total association between SNP5 (rs932477) in intron 4 with cortical
      thickness and buckling ratio was detected (single locus analyses: P=0.035 and
      0.041, respectively). Haplotype analyses further supported the above association
      (P=0.010 and 0.004, respectively). Similar patterns of associations with the
      studied SNPs and their haplotypes were present in subsamples stratified by sex,
      too. However, after permutation tests, the empirical significance level was set
      as P<0.011, which renders most associations insignificant. Therefore, we
      concluded that polymorphisms in the ER-alpha gene were nominally associated with
      femoral neck (FN) geometry variables estimated from DXA. Such genetic effects on
      hip geometry were not sex specific.

PMID- 16292602
TI  - A personal recollection.

PMID- 16292603
TI  - In defense of paternalism.
AB  - This paper argues that we have wrongly and not for the patient's benefit made a
      form of stark autonomy our highest value which allows physicians to slip out from
      under their basic duty which has always been to pursue a particular patient's
      good. In general - I shall argue - it is the patient's right to select his or her
      own goals and the physician's duty to inform the patient of the feasibility of
      that goal and of the means needed to attain it. If the goal is not one that is
      possible, the patient, with the physician and family, must select a feasible goal
      and then discuss the costs/benefits of various approaches. The physician should
      take a leading role in helping the patient select the goal. I argue that to
      simply present a laundry list of means and insist that patients choose for
      themselves is not only abandoning patients to their autonomy but is, in fact, a
      crass form of violating the patient's autonomy. Freely choosing not to choose is
      a choice a patient with decisional capacity is entitled to make and one that
      needs to be respected.

PMID- 16292604
TI  - Some things ought never be done: moral absolutes in clinical ethics.
AB  - Moral absolutes have little or no moral standing in our morally diverse modern
      society. Moral relativism is far more palatable for most ethicists and to the
      public at large. Yet, when pressed, every moral relativist will finally admit
      that there are some things which ought never be done. It is the rarest of moral
      relativists that will take rape, murder, theft, child sacrifice as morally
      neutral choices. In general ethics, the list of those things that must never be
      done will vary from person to person. In clinical ethics, however, the nature of
      the physician-patient relationship is such that certain moral absolutes are
      essential to the attainment of the good of the patient - the end of the
      relationship itself. These are all derivatives of the first moral absolute of all
      morality: Do good and avoid evil. In the clinical encounter, this absolute
      entails several subsidiary absolutes - act for the good of the patient, do not
      kill, keep promises, protect the dignity of the patient, do not lie, avoid
      complicity with evil. Each absolute is intrinsic to the healing and helping ends
      of the clinical encounter.

PMID- 16292605
TI  - "Diseases and natural kinds".
AB  - David Thomasma called for the development of a medical ethics based squarely on
      the philosophy of medicine. He recognized, however, that widespread anti
      essentialism presented a significant barrier to such an approach. The aim of this
      article is to introduce a theory that challenges these anti-essentialist
      objections. The notion of natural kinds presents a modest form of essentialism
      that can serve as the basis for a foundationalist philosophy of medicine. The
      notion of a natural kind is neither static nor reductionistic. Disease can be
      understood as making necessary reference to living natural kinds without invoking
      the claim that diseases themselves are natural kinds. The idea that natural kinds
      have a natural disposition to flourish as the kinds of things that they are
      provides a telos to which to tether the notion of disease - an objective telos
      that is broader than mere survival and narrower than subjective choice. It is
      argued that while nosology is descriptive and may have therapeutic implications,
      disease classification is fundamentally explanatory. Sickness and illness, while
      referring to the same state of affairs, can be distinguished from disease
      phenomenologically. Scientific and diagnostic fallibility in making judgments
      about diseases do not diminish the objectivity of this notion of disease.
      Diseases are things, not kinds. Injury is a concept parallel to disease that also
      makes necessary reference to living natural kinds. These ideas provide a new
      possibility for the development of a philosophy of medicine with implications for
      medical ethics.

PMID- 16292606
TI  - "Suspended animation," my mother's wife and cultural discernment: considerations
      for genetic research among immigrants.
AB  - One of the most difficult contemporary issues facing the bioethics of clinical
      research is balancing the maintaining of a universality of ethics standards with
      a sensitivity to cultural issues and differences. The concept of "vulnerability"
      for research subjects is especially apt for investigating the ethical and
      cultural issues surrounding the conduct of genetic research among new immigrants
      to the United States, using the Sudanese Nuer and Dinka tribes, recently settled
      in the Midwest, as an example. Issues of cultural vulnerability arise for some
      immigrants, related to relationship to the earth and to kinship issues, that
      threaten the narrative richness of a subject's life as well as the way she
      situates herself in the world.

PMID- 16292608
TI  - The human body as field of conflict between discourses.
AB  - The approach to AIDS as a disease and a threat for social discrimination is used
      as an example to illustrate a conceptual thesis. This thesis is a claim that
      concerns what we call a medical issue or not, what is medicalised or needs to be
      demedicalised. In the friction between medicalisation and demedicalisation as
      discursive strategies the latter approach can only be effected through the
      employment of discourses or discursive strategies other than medicine, such as
      those of the law and of economics. These discourses each realise different
      values, promote a different subject, and have a different concept of man. The
      concept of discourse is briefly outlined against concepts such as the linear
      growth concept of science and the growth model of science as changes in paradigm.
      The issue of testing for AIDS shows a conflict between the medical and the legal
      discourse and illustrates the title of our contribution: the human body as field
      of conflict between discourses.

PMID- 16292609
TI  - Dialogue with David C. Thomasma and Renzo Pegoraro.

PMID- 16292607
TI  - Human rights, cultural pluralism, and international health research.
AB  - In the field of bioethics, scholars have begun to consider carefully the impact
      of structural issues on global population health, including socioeconomic and
      political factors influencing the disproportionate burden of disease throughout
      the world. Human rights and social justice are key considerations for both
      population health and biomedical research. In this paper, I will briefly explore
      approaches to human rights in bioethics and review guidelines for ethical conduct
      in international health research, focusing specifically on health research
      conducted in resource-poor settings. I will demonstrate the potential for
      addressing human rights considerations in international health research with
      special attention to the importance of collaborative partnerships, capacity
      building, and respect for cultural traditions. Strengthening professional
      knowledge about international research ethics increases awareness of ethical
      concerns associated with study design and informed consent among researchers
      working in resource-poor settings. But this is not enough. Technological and
      financial resources are also necessary to build capacity for local communities to
      ensure that research results are integrated into existing health systems.
      Problematic issues surrounding the application of ethical guidelines in resource
      poor settings are embedded in social history, cultural context, and the global
      political economy. Resolving the moral complexities requires a commitment to
      engaged dialogue and action among investigators, funding agencies, policy makers,
      governmental institutions, and private industry.

PMID- 16292610
TI  - From atherosclerotic coronary ectasia to aneurysm: a case report and literature
      review.
AB  - In contrast to Kawasaki syndrome the formation of coronary aneurysms caused by
      atherosclerosis has hardly been demonstrated. We report on a 56-year old patient,
      admitted to our hospital for cardiovascular evaluation before carotid surgery. He
      had no anginal pain, but a history of coronary artery disease with previous
      anterior myocardial infarction. Angiography revealed a collateralized LAD
      occlusion. Myocardial scintigraphy only demonstrated fixed perfusion defects.
      Surprisingly, MR imaging revealed large coronary aneurysms of the RCX and RCA.
      Angiographic follow up showed a rapid progression of ectatic towards aneurysmatic
      coronary lesions within 3 years. General pathophysiological mechanisms promoting
      ectatic coronary artery disease as a structural failure of the atherosclerotic
      remodelling process itself and chronic dilatatory stimuli due to endogenous and
      exogenous factors are discussed.

PMID- 16292611
TI  - Substructural fragments: an universal language to encode reactions, molecular and
      supramolecular structures.
AB  - Substructural fragments are proposed as a simple and safe way to encode molecular
      structures in a matrix containing the occurrence of fragments of a given type.
      The knowledge retrieved from QSPR modelling can also be stored in that matrix in
      addition to the information about fragments. Complex supramolecular systems
      (using special bond types) and chemical reactions (represented as Condensed
      Graphs of Reactions, CGR) can be treated similarly. The efficiency of fragments
      as descriptors has been demonstrated in QSPR studies of aqueous solubility for a
      diverse set of organic compounds as well as in the analysis of thermodynamic
      parameters for hydrogen-bonding in some supramolecular complexes. It has also
      been shown that CGR may be an interesting opportunity to perform similarity
      searches for chemical reactions. The relationship between the density of
      information in descriptors/knowledge matrices and the robustness of QSPR models
      is discussed.

PMID- 16292613
TI  - Surrogate docking: structure-based virtual screening at high throughput speed.
AB  - Structure-based screening using fully flexible docking is still too slow for
      large molecular libraries. High quality docking of a million molecule library can
      take days even on a cluster with hundreds of CPUs. This performance issue
      prohibits the use of fully flexible docking in the design of large combinatorial
      libraries. We have developed a fast structure-based screening method, which
      utilizes docking of a limited number of compounds to build a 2D QSAR model used
      to rapidly score the rest of the database. We compare here a model based on
      radial basis functions and a Bayesian categorization model. The number of
      compounds that need to be actually docked depends on the number of docking hits
      found. In our case studies reasonable quality models are built after docking of
      the number of molecules containing approximately 50 docking hits. The rest of the
      library is screened by the QSAR model. Optionally a fraction of the QSAR
      prioritized library can be docked in order to find the true docking hits. The
      quality of the model only depends on the training set size - not on the size of
      the library to be screened. Therefore, for larger libraries the method yields
      higher gain in speed no change in performance. Prioritizing a large library with
      these models provides a significant enrichment with docking hits: it attains the
      values of approximately 13 and approximately 35 at the beginning of the score
      sorted libraries in our two case studies: screening of the NCI collection and a
      combinatorial libraries on CDK2 kinase structure. With such enrichments, only a
      fraction of the database must actually be docked to find many of the true hits.
      The throughput of the method allows its use in screening of large compound
      collections and in the design of large combinatorial libraries. The strategy
      proposed has an important effect on efficiency but does not affect retrieval of
      actives, the latter being determined by the quality of the docking method itself.

PMID- 16292612
TI  - Influence of conformation on the representation of small flexible molecules at
      low resolution: alignment of endothiapepsin ligands.
AB  - In this contribution, we discuss a molecular representation mode for the
      generation of reduced descriptions of flexible molecules in various
      conformations. The representations of the endothiapepsin ligands are constituted
      by graphs of peaks obtained through a hierarchical merging algorithm which
      combines the location of promolecular electron density (ED) maxima with the
      decomposition of the molecular structures into fragments. The representations are
      then aligned through the use of a Monte Carlo/Simulated Annealing procedure. The
      evaluation function of the alignment solutions is based on the local density
      values of the peaks and their inter-distances. The applications show that the
      alignment of a given molecule onto itself, in a different conformation, is
      successful when a pseudo-topological path length is considered in the evaluation
      function of the solution, while Cartesian distances are more adapted to the
      scoring for alignments of two different molecules in their co-crystallized
      conformation. Results are compared with the available literature data.

PMID- 16292616
TI  - A review of interspecies toxicity extrapolation in birds and mammals and a
      proposal for long-term toxicity data.
AB  - Terrestrial risk assessments for pesticide exposure is generally based on a
      limited number of toxicity data. The protection target for these assessments
      requires an extrapolation from species for which toxicity data are available to
      other species with unknown sensitivity to be able to protect these as well. Our
      ability to extrapolate toxicity endpoints between species is a major source of
      uncertainty in risk assessment. Most analyses of interspecies extrapolation in
      avian risk assessments have dealt with acute toxicity data. It was suggested
      that, in the absence of a strong rationale to the contrary, we should assume that
      reproductive data is at least as variable as acute data and that strategies
      developed for acute data could be applied to long term toxicity data as well.
      Considering only the two main bird test species for which reproduction data are
      available (Mallard and Northern Bobwhite), a comparison of the interspecies
      standard deviation for both acute and reproduction data suggests that the two are
      equally variable. Analysis of a very limited data set also suggests that this
      conclusion holds regardless of which endpoint is triggered in the reproduction
      study. However, the relative sensitivity of the two species established from
      acute test data appears to be reversed in the case of reproductive data. In
      addition there seems to be no reason to believe that bodyweight is a factor in
      helping birds cope with the rigors of chronic dosing, which is in contrast with
      the acute dosing situation. This suggests that the best extrapolation technique
      for reproduction test data should be independent of phylogeny and independent of
      bodyweight scaling. The simplest such method is the one that was proposed by
      Luttik and Aldenberg (1995, 1997) for both birds and mammals.

PMID- 16292615
TI  - The integration of cell proliferation and growth in leaf morphogenesis.
AB  - A number of recent publications have assessed the outcome on leaf development of
      targeted manipulation of cell proliferation. The results of these investigations
      have awakened interest in the long-standing debate in plant biology on the
      precise role of cell division in morphogenesis. Does cell proliferation drive
      morphogenesis (cell theory) or is it subservient to a mechanism which acts at the
      whole organ level to regulate morphogenesis (organismal theory)? In this review,
      the central role of growth processes (distinct from cell proliferation) in
      morphogenesis is highlighted and the limitations in our understanding of the
      basic mechanisms of plant growth control are highlighted. Finally, an attempt is
      made to demonstrate how sequential local co-ordination of growth might provide an
      interpretation of some of the recent observations on cell proliferation and leaf
      morphogenesis.

PMID- 16292614
TI  - Low level laser irradiation stimulates osteogenic phenotype of mesenchymal stem
      cells seeded on a three-dimensional biomatrix.
AB  - Mesenchymal stem cells (MSCs) seeded on three-dimensional (3D) coralline (Porites
      lutea) biomatrices were irradiated with low-level laser irradiation (LLLI). The
      consequent phenotype modulation and development of MSCs towards ossified tissue
      was studied in this combined 3D biomatrix/LLLI system and in a control group,
      which was similarly grown, but was not treated by LLLI. The irradiated and non
      irradiated MSC were tested at 1-7, 10, 14, 21, 28 days of culturing via analysis
      of cellular distribution on matrices (trypan blue), calcium incorporation to
      newly formed tissue (alizarin red), bone nodule formation (von Kossa), fat
      aggregates formation (oil red O), alkaline phosphatase (ALP) activity, scanning
      electron microscopy (SEM) and electron dispersive spectrometry (EDS). The results
      obtained from the irradiated samples showed enhanced tissue formation, appearance
      of phosphorous peaks and calcium and phosphate incorporation to newly formed
      tissue. Moreover, in irradiated samples ALP activity was significantly enhanced
      in early stages and notably reduced in late stages of culturing. These findings
      of cell and tissue parameters up to 28 days of culture revealed higher
      ossification levels in irradiated samples compared with the control group. We
      suggest that both the surface properties of the 3D crystalline biomatrices and
      the LLLI have biostimulatory effects on the conversion of MSCs into bone-forming
      cells and on the induction of ex-vivo ossification.

PMID- 16292617
TI  - A new interpretation of avian and Mammalian reproduction toxicity test data in
      ecological risk assessment.
AB  - The long-term risks of pesticides to wildlife in the EU currently are assessed by
      comparing the lowest no-observed-effect concentration (NOEC) determined from the
      suite of endpoints measured in existing avian and mammalian laboratory
      reproduction tests with estimated exposure concentrations by calculating Toxicity
      to Exposure Ratios (TERs). Regulatory authorities experience difficulties when
      assessing long-term risks because of the lack of accepted methods to improve the
      ecological realism of exposure and toxicity estimates and understand risks at a
      population level. This paper describes an approach for interpreting existing
      avian and mammalian toxicity test data that divides breeding cycles into several
      discrete phases and identifies specific test endpoints as indicators of direct
      pesticide effects possible at each phase. Based on the distribution of breeding
      initiation dates for a species of concern and the dates of pesticide
      applications, this approach compares the phase-specific toxicity endpoint with
      the expected pesticide exposure levels during each of the breeding phases. The
      fate of each breeding attempt is determined through a series of decision points.
      The cumulative reproductive response of individuals in a breeding population
      based on this decision framework provides a means of examining the estimated
      risks over the course of the breeding season and deriving an overall metric of
      the impact of the pesticide on reproduction. Research needed to further improve
      the approach is discussed.

PMID- 16292619
TI  - Diagnosis and surgical treatment of colonic duplication in a young woman.

PMID- 16292621
TI  - Mid pouch strictureplasty for Crohn's disease after ileal-pouch anal anastomosis:
      an alternative to pouch excision.

PMID- 16292618
TI  - Improved approaches to assessing long-term risks to birds and mammals.

PMID- 16292622
TI  - Low anterior intersphincteric resection, total mesorectal excision, coloplasty
      and coloanal anastomosis with neoanal smooth muscle encirclement for low rectal
      cancer.

PMID- 16292623
TI  - Transcending the silos: toward an interdisciplinary approach to end-of-life care
      in the ICU.

PMID- 16292624
TI  - Nurse involvement in end-of-life decision making: the ETHICUS Study.
AB  - OBJECTIVE: The purpose was to investigate physicians' perceptions of the role of
      European intensive care nurses in end-of-life decision making. DESIGN: This study
      was part of a larger study sponsored by the Ethics Section of the European
      Society of Intensive Care Medicine, the ETHICUS Study. Physicians described
      whether they thought nurses were involved in such decisions, whether nurses
      initiated such a discussion and whether there was agreement between physicians
      and nurses. The items were analyzed and comparisons were made between different
      regions within Europe. SETTING: The study took place in 37 intensive care units
      in 17 European countries. PATIENTS AND PARTICIPANTS: Physician investigators
      reported data related to patients from 37 centers in 17 European countries.
      INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Physicians perceived nurses as
      involved in 2,412 (78.3%) of the 3,086 end-of-life decisions (EOLD) made. Nurses
      were thought to initiate the discussion in 66 cases (2.1%), while ICU physicians
      were cited in 2,438 cases (79.3%), the primary physician in 328 cases (10.7%),
      the consulting physician in 105 cases (3.4%), the family in 119 cases (3.9%) and
      the patient in 19 cases (0.6%). In only 20 responses (0.6%) did physicians report
      disagreement between physicians and nurses related to EOLD. A significant
      association was found between the region and responses to the items related to
      nursing. Physicians in more northern regions reported more nurse involvement.
      CONCLUSIONS: Physicians perceive nurses as involved to a large extent in EOLDs,
      but not as initiating the discussion. Once a decision is made, there is a sense
      of agreement. The level of perceived participation is different for different
      regions.

PMID- 16292625
TI  - Measuring satisfaction in family members of critically ill cancer patients in
      Brazil.
AB  - OBJECTIVE: To assess the determinants for satisfaction of cancer patients' family
      members with the intensive care unit. DESIGN: Prospective cohort study. SETTING:
      A 13-bed intensive care unit in a tertiary cancer centre. PATIENTS AND
      PARTICIPANTS: 164 families of consecutive patients with a length of stay greater
      than 48 h. INTERVENTION: None. MEASUREMENT: A modified version of the Critical
      Care Family Needs Inventory was applied and compared with the families'
      perception of prognosis, previous information given to them, and patients'
      severity of disease (SAPS). RESULTS: The median score of the questionnaire was 11
      (2-14), and the cut-off for satisfaction was established at 9 (1st quartile).
      SAPS >41 was associated with lower satisfaction [(p<0.05, chi-square, OR 2.49 (CI
      1.1-5.4)]. When those interviewed surmised a prognosis different from the final
      outcome [p<0.05, chi-square, OR 2.70 (1.2-6.0)], a significant association with
      dissatisfaction was found. CONCLUSION: More discussion about prognosis may
      improve the level of satisfaction of cancer patients' family members with the
      intensive care unit.

PMID- 16292627
TI  - Echocardiography in the ICU: time for widespread use!

PMID- 16292626
TI  - Echocardiography in the critically ill: current and potential roles.
AB  - BACKGROUND: The use of echocardiography in the critically ill presents specific
      challenges. However, information of direct relevance to clinical management can
      be obtained relating to abnormalities of structure and function and can be used
      to estimate pulmonary arterial and venous pressures. DISCUSSION: Investigation of
      the consequences of myocardial ischaemia, valvular dysfunction and pericardial
      disease can be facilitated, and changes characteristic of specific conditions
      (e.g. sepsis, pulmonary thromboembolism) detected. Echocardiography can also be
      used to monitor the effects of therapeutic interventions. CONCLUSIONS: The
      applications of echocardiography in the critical care setting (excluding standard
      peri-operative echocardiography for cardiac surgery) are reviewed, with
      particular emphasis on the assessment of cardiac physiology.

PMID- 16292628
TI  - Increased rate of dicentric chromosomes in French Polynesian thyroid cancer
      patients?

PMID- 16292631
TI  - [Considerations on a room for leave taking].
AB  - Many patients die in hospitals and care centers. It is therefore necessary to
      create an environment for the dying person, as well as for relatives, which
      allows death to occur with dignity while also permitting a dignified farewell. A
      special room should be available for taking leave of the loved one and for the
      mourning of the relatives. This room should, as far as possible, be neutrally
      decorated while at the same time it should be appropriate for various cultures
      and religious requirements. In order to be able to take leave symbolically, it is
      necessary to place the departed in the light, for example from a window.

PMID- 16292630
TI  - Ability of FDG-PET to detect all cancers in patients with familial adenomatous
      polyposis, and impact on clinical management.
AB  - PURPOSE: Familial adenomatous polyposis (FAP) is characterised by colonic and
      duodenal adenomatous polyps that carry a risk of malignant transformation.
      Malignant degeneration of duodenal adenomas is difficult to detect. We speculated
      that 2-((18)F)-fluoro-2-deoxy-D: -glucose positron emission tomography (FDG-PET)
      might be able to detect early duodenal cancer in FAP. Accordingly, we
      investigated the role of FDG-PET in the management of FAP patients. METHODS: FDG
      PET was performed in 24 FAP patients. Eight had advanced duodenal adenomas
      (Spigelman IV), including two patients with duodenal cancer. Scans were defined
      as positive on the basis of focal FDG accumulation. RESULTS: Pathological FDG
      accumulation was absent in 19 of 24 patients. All six patients with Spigelman IV
      duodenal adenomas (without cancer) were negative; two of these underwent a
      duodenectomy and pathological examination did not reveal duodenal cancer. In five
      patients, FDG-PET revealed significant uptake, in the duodenum (2), lower abdomen
      (1), lung (1) and multiple sites in the abdomen (1). These hot spots correlated
      with duodenal cancer (2), abdominal metastasis (1) and sclerosing haemangioma of
      the lung (1). We failed to make a histopathological diagnosis in the single
      patient with multiple intra-abdominal sites of FDG uptake. None of the patients
      from the FDG-PET-negative group developed cancer during follow-up (mean 2.8
      years). CONCLUSION: FDG-PET detected all the cancers present, and none of the
      patients with negative FDG-PET developed cancer. This suggests that positive FDG
      PET in FAP patients should lead to further examinations to rule out cancer. In
      patients with negative FDG-PET a more conservative approach seems justified.

PMID- 16292632
TI  - Differential activation of astrocytes and microglia after spinal cord injury in
      the fetal rat.
AB  - BACKGROUND: As the immature spinal cord was nerve growth permissive, we examined
      glial reactions that influence regeneration of the spinal cord in a fetal rat
      spinal cord injury model. METHODS: Three, 7, 21, and 35 days after intrauterine
      surgery, offspring were killed and the thoracic and lumbar spinal cords were
      carefully removed from the spinal column and then cut into 10 mum longitudinal
      sections. These sections were stained with hematoxylin-eosin, anti-glial
      fibrillary acidic protein antibody (GFAP) as a marker of astrocytes, and anti
      complement CR3 antibody (OX-42) as a marker of microglia. A cordotomy model in a
      young adult rat was utilized as a control. RESULTS: In the present study,
      collagen fibers and scar formation were seen in the severed spinal cords of
      mature rats, but scar formation was not seen in the fetal rat cordotomy group,
      regardless of spinal continuity. In the control group, biological activity of
      GFAP-positive cells increased over time. In the fetal rat cordotomy model,
      activity elevated slightly immediately after cordotomy, and disappeared shortly
      thereafter. In the control group, OX-42-positive macrophage-like cells
      proliferated over time. However, in the fetal rat cordotomy model, OX-42-
      positive macrophage-like cells were recognized on postoperative days 3 and 7, and
      then disappeared. At 5 mm from the cordotomy site, reactive microglia were
      recognized in the white matter of control group spinal cords, but these microglia
      were not recognized in the fetal rat cordotomy model. CONCLUSIONS: In the present
      study, collagen fibers and scar formation were seen in the severed spinal cords
      of adult rats, but scar formation was not seen in the fetal rat cordotomy group.
      Lack of inflammation and scar formation thus appear advantageous for regeneration
      of the fetal spinal cord. Between fetal and mature rats, chronological changes in
      the immunohistochemical reactions of astrocytes and microglia following cordotomy
      were compared, and the results confirmed many differences. The results of the
      present study suggest that the presence of activated glial cells around damaged
      central nervous tissue and the quick disappearance of these cells after injury
      are important for the repair of damaged central nervous system tissue, and that
      the role of glial cells in nerve regeneration can change depending on the level
      of maturity of glial cells or surrounding cells, site of injury, or the state of
      tissue around the injury.

PMID- 16292634
TI  - The rationale for a spine registry.
AB  - In the discussion about the rationale for spine registries, two basic questions
      have to be answered. The first one deals with the value of orthopaedic registries
      per se, considering them as observational studies and comparing the evidence they
      generate with that of randomised controlled trials. The second question asks if
      the need for registries in spine surgery is similar to that in the arthroplasty
      sector. The widely held view that randomised controlled trials are the 'gold
      standard' for evaluation and that observational methods have little or no value
      ignores the limitations of randomised trials. They may prove unnecessary,
      inappropriate, impossible, or inadequate. In addition, the external validity and
      hence the ability to make generalisations about the results of randomised trials
      is often low. Therefore, the false conflict between those who advocate randomised
      trials in all situations and those who believe observational data provide
      sufficient evidence needs to be replaced with mutual recognition of their
      complementary roles. The fact that many surgical techniques or technologies were
      introduced into the field of spine surgery without randomised trials or
      prospective cohort comparisons makes obvious an even increased need for spine
      registries compared to joint arthroplasty. An essential methodological
      prerequisite for a registry is a common terminology for reporting results and a
      sophisticated technology that networks all participants so that one central data
      pool is created and accessed. Recognising this need, the Spine Society of Europe
      has researched and developed Spine Tango, the first European spine registry,
      which can be accessed under www.eurospine.org.

PMID- 16292633
TI  - Back related outcome assessment instruments.
AB  - A literature review of the most widely used condition specific, self administered
      assessment questionnaires for low back pain had been undertaken. General and
      historic aspects, reliability, responsiveness and minimum clinically important
      difference, external validity, floor and ceiling effects, and available languages
      were analysed. These criteria, however, are only part of the consideration. Of
      similar importance are the content, wording of questions and answers in each of
      the six questionnaires and an analysis of the different score results. The issue
      of score bias is discussed and suggestions are given in order to increase the
      construct validity in the practical use of the individual questionnaires.

PMID- 16292636
TI  - Vestibular-Podokinetic interaction without vestibular perception.
AB  - After prolonged stepping in place relative to space over the center of a rotating
      turntable, blindfolded subjects cannot step on the stationary platform without
      unknowingly turning themselves relative to space, a phenomenon termed podokinetic
      after rotation (PKAR). We asked what role the resulting vestibular stimulation
      might play in the expression of this form of PKAR. A method of servo-stabilizing
      the body relative to space during PKAR was devised to compare PKAR expression
      with and without significant vestibular stimulation. Simulated estimates of
      average central vestibular response profiles were obtained by passing the
      averaged unidirectional body angular velocity profiles relative to space through
      a first-order model of the canal system (tau=15 s). Such simulation results
      suggested that during normal PKAR performed on a stationary platform, the average
      central vestibular response would likely rise to peak levels equivalent to that
      induced by about 9 degrees /s within the frequency range of natural head
      movement. In the servo-stabilized condition, the simulated response was reduced
      to insignificant levels. Experimental results demonstrated that in the
      unstabilized condition the rate of rise of PKAR angular velocity was roughly four
      times slower than in the stabilized condition. We conclude that the normal
      expression of PKAR conducted on a stationary platform tends to be substantially
      slowed by interaction with an unperceived vestibular response.

PMID- 16292635
TI  - Percutaneous discography: comparison of low-dose CT, fluoroscopy and MRI in the
      diagnosis of lumbar disc disruption.
AB  - AIM: To compare the diagnostic accuracy of low-dose computed tomography (CT),
      magnetic resonance imaging (MRI) and fluoroscopy in percutaneous discography in
      patients scheduled for lumbar spondylodesis. MATERIAL AND METHODS: Within a
      prospective pilot study, 18 disc segments of 11 patients with radicular or
      pseudoradicular pain prior to anteroposterior spondylodesis were evaluated. After
      injection of a mixture of non-ionic iodine-containing contrast agent and
      gadolinium-based contrast medium into the disc spaces, all patients underwent
      conventional fluoroscopy, as well as low-dose CT and MRI. The occurrence of
      memory pain during contrast injection was recorded. CT, MRI and fluoroscopic
      images were analyzed independently by two readers blinded to the clinical
      findings. RESULTS: There was 100% agreement between CT and MRI discography in the
      detection, localization and grading of degenerative changes. In contrast,
      conventional fluoroscopy identified only 9 of the 12 abnormal segments. Memory
      pain following puncture was identified in 3 of the 12 affected segments. SUMMARY:
      Low-dose CT and MRI discography have a similar accuracy in the assessment of disc
      disruption and they are superior to fluoroscopic discography.

PMID- 16292637
TI  - Spatial attention affects sensorimotor reorganisation in human motor cortex.
AB  - It is well known that the somatotopic representation of sensory and motor
      cortices reorganises in response to sustained changes in sensory input. It is
      also clear that the extent of the effect depends on whether or not subjects pay
      attention during the procedure. Here we show that the pattern of reorganisation
      produced by sustained sensory input depends not only on the subjects' attention
      but also on the spatial focus of their attention on the body surface. Maximal
      effects are observed only when subjects pay attention to the site of the input;
      if they attend to an adjacent body part then the effects are reduced. These
      results may be relevant to rehabilitation procedures commonly used in patients
      after stroke.

PMID- 16292638
TI  - Muller-Lyer figures influence the online reorganization of visually guided
      grasping movements.
AB  - In advance of grasping a visual object embedded within fins-in and fins-out
      Muller-Lyer (ML) configurations, participants formulated a premovement grip
      aperture (GA) based on the size of a neutral preview object. Preview objects were
      smaller, veridical, or larger than the size of the to-be-grasped target object.
      As a result, premovement GA associated with the small and large preview objects
      required significant online reorganization to appropriately grasp the target
      object. We reasoned that such a manipulation would provide an opportunity to
      examine the extent to which the visuomotor system engages egocentric and/or
      allocentric visual cues for the online, feedback-based control of action. It was
      found that the online reorganization of GA was reliably influenced by the ML
      figures (i.e., from 20 to 80% of movement time), regardless of the size of the
      preview object, albeit the small and large preview objects elicited more robust
      illusory effects than the veridical preview object. These results counter the
      view that online grasping control is mediated by absolute visual information
      computed with respect to the observer (e.g., Glover in Behav Brain Sci 27:3-78,
      2004; Milner and Goodale in The visual brain in action 1995). Instead, the impact
      of the ML figures suggests a level of interaction between egocentric and
      allocentric visual cues in online action control.

PMID- 16292639
TI  - Finger movements during reach-to-grasp in the monkey: amplitude scaling of a
      temporal synergy.
AB  - To reduce the complexity of controlling hand-shaping, recent evidence suggests
      that the central nervous system uses synergies. In this study, two Rhesus monkeys
      reached-to-grasp 15 objects, varying in geometric properties, at five grasp force
      levels. Hand kinematics were recorded using a video-based tracking system.
      Individual finger movements were described as vectors varying in length and
      angle. Inflection points (i.e., stereotypic minima/maxima in the temporal profile
      of each finger vector) exhibited a temporal synchrony for individual fingers and
      in the coupling across fingers. Inflection point amplitudes varied significantly
      across objects grasped, scaling linearly with the object grasp dimension. Thus,
      differences in the vectors as a function of the objects were in the relative
      scaling of the vector parameters over time rather than a change in the temporal
      structure. Mahalanobis distance analysis of the inflection points confirmed that
      changes in inflection point amplitude as a function of objects were greater than
      changes in timing. Inflection points were independent of the grasp force,
      consistent with the observation that reach-to-grasp kinematics and grasp force
      are controlled independently. In summary, the shaping of the hand during reach-to
      grasp involves scaling the amplitude of highly stereotypic temporal movements of
      the fingers.

PMID- 16292640
TI  - Adaptation and generalization in acceleration-dependent force fields.
AB  - Any passive rigid inertial object that we hold in our hand, e.g., a tennis
      racquet, imposes a field of forces on the arm that depends on limb position,
      velocity, and acceleration. A fundamental characteristic of this field is that
      the forces due to acceleration and velocity are linearly separable in the
      intrinsic coordinates of the limb. In order to learn such dynamics with a
      collection of basis elements, a control system would generalize correctly and
      therefore perform optimally if the basis elements that were sensitive to limb
      velocity were not sensitive to acceleration, and vice versa. However, in the
      mammalian nervous system proprioceptive sensors like muscle spindles encode a
      nonlinear combination of all components of limb state, with sensitivity to
      velocity dominating sensitivity to acceleration. Therefore, limb state in the
      space of proprioception is not linearly separable despite the fact that this
      separation is a desirable property of control systems that form models of
      inertial objects. In building internal models of limb dynamics, does the brain
      use a representation that is optimal for control of inertial objects, or a
      representation that is closely tied to how peripheral sensors measure limb state?
      Here we show that in humans, patterns of generalization of reaching movements in
      acceleration-dependent fields are strongly inconsistent with basis elements that
      are optimized for control of inertial objects. Unlike a robot controller that
      models the dynamics of the natural world and represents velocity and acceleration
      independently, internal models of dynamics that people learn appear to be rooted
      in the properties of proprioception, nonlinearly responding to the pattern of
      muscle activation and representing velocity more strongly than acceleration.

PMID- 16292641
TI  - Ketamine attenuates glutamate-induced mechanical sensitization of the masseter
      muscle in human males.
AB  - The purpose of the present study was to determine whether glutamate-induced
      mechanical sensitization of the masseter muscle in human volunteers involves
      activation of peripheral N-methyl-D-aspartate (NMDA) receptors. Healthy male
      volunteers (n=18) participated in this randomized, two-session study. During each
      session, the volunteers received two injections into the right masseter muscle.
      An initial injection of glutamate (1 M, 0.2 ml) alone was followed 30 min later
      by a second injection of glutamate alone or glutamate combined with ketamine (10
      mM). Pressure pain threshold (PPT) was assessed over the right masseter muscle at
      and 2 cm above the injection site, as well as over the right temporalis muscle
      and left masseter muscle prior to the first injection. The PPT was reassessed at
      all four sites every 5 min from 10 to 30 min after the second injection and once
      again 60 min after the second injection. Glutamate-evoked muscle pain, pain area
      and the sensory pain response index of the McGill pain questionnaire were all
      significantly reduced by co-injection of ketamine. The mean PPT values were
      significantly decreased by approximately 10%, 10, 15 and 25 min after injection
      of glutamate, but only over the site of injection. Co-injection of ketamine with
      glutamate also completely blocked the glutamate-induced mechanical sensitization
      15 min post-injection as compared with glutamate alone. The lack of spread of
      mechanical sensitization outside the area of glutamate injection is consistent
      with the view that glutamate-induced mechanical sensitization results from a
      peripheral mechanism. The attenuation of glutamate-induced mechanical
      sensitization by ketamine suggests that this effect is mediated, in part, through
      activation of peripheral NMDA receptors.

PMID- 16292642
TI  - Gravitational influences on reference frames for mapping somatic stimuli in brain
      damaged patients.
AB  - Previous studies have shown that the manipulation of body position in space can
      modulate the manifestations of visual neglect. Here, we investigated in right
      brain-damaged patients (RBD) the possible influence of gravitational inputs on
      the capability to detect tactile stimuli delivered to hands positioned in
      ipsilesional or contralesional space. RBD patients (with or without impairments
      in detecting contralesional stimuli under single and double stimulation
      conditions) and healthy control subjects were tested in a tactile detection task
      in which gravitational (upright vs. supine) and hand position (anatomical vs.
      crossed) variables were orthogonally varied. The postural manipulation of the
      entire body turned out to influence the degree of tactile detection. In
      particular, RBD patients with tactile deficits detected a significantly higher
      number of left-sided stimuli in the supine posture than in the upright posture.
      Moreover, crossing of hands improved the ability of RBD patients with tactile
      deficits in detecting stimuli delivered to their left contralesional hand. The
      beneficial effect of lying supine was independent of the spatial position of the
      hands, thus suggesting that the improvement of performance dependent upon entire
      body posture and that dependent upon crossing hands may rely upon separate
      mechanisms.

PMID- 16292643
TI  - Projections of the ventrolateral pontine vocalization area in the squirrel
      monkey.
AB  - In four squirrel monkeys (Saimiri sciureus), the tracer biotin dextranamine (BDA)
      was injected into the ventrolateral pons at a site at which injection of the
      glutamate antagonist kynurenic acid blocked vocalization electrically elicited
      from the periaqueductal gray (PAG). Anterograde projections could be traced into
      all cranial motor and sensory nuclei involved in phonation, that is, the nucleus
      ambiguus, facial, hypoglossal and trigeminal motor nuclei, the motorneuron column
      in the ventral gray substance innervating the extrinsic laryngeal muscles, the
      nucleus retroambiguus, solitary tract and spinal trigeminal nuclei. Projections
      were also found into a number of auditory nuclei, namely the nucleus cochlearis
      complex, superior olive, ventral and dorsal nuclei of the lateral lemniscus and
      inferior colliculus. Furthermore, there were projections into the reticular
      formation of the lateral and dorsocaudal medulla and lateral pons, into nucleus
      gracilis, inferior and medial vestibular nuclei, lateral reticular nucleus,
      ventral raphe, pontine gray, superior colliculus, PAG and mediodorsal thalamic
      nucleus. Injection of the tracer wheat germ agglutinin-conjugated horseradish
      peroxidase into the ventrolateral pontine vocalization-blocking area in one
      animal yielded retrograde labeling throughout the PAG. Injection of BDA into a
      vocalization-eliciting site of the PAG in another animal yielded projections into
      the ventrolateral pontine vocalization-blocking area. It is concluded that the
      ventral paralemniscal area in the ventrolateral pons represents a relay station
      of the descending periaqueductal vocalization-controlling pathway.

PMID- 16292644
TI  - Prenatal MR diffusion-weighted imaging in a fetus with hemimegalencephaly.
AB  - We report a case of hemimegalencephaly diagnosed by prenatal MRI with an emphasis
      on its appearance on diffusion-weighted images. This case shows that in this
      condition the enlarged hemisphere may show restricted diffusion on prenatal MRI.
      In our opinion, this finding may result from a combination of increased
      cellularity and advanced myelination in the affected hemisphere. Restricted
      diffusion is an additional valuable indicator in the analysis of the fetal brain.

PMID- 16292645
TI  - Effect of chaotropic anions on the sodium transport by the Na,K-ATPase.
AB  - The effect of choline iodide, bromide and chloride on the kinetics of the
      electrogenic sodium transport by the Na,K-ATPase was investigated in a model
      system of ATPase-containing membrane fragments adsorbed on the lipid bilayer
      membrane. The kinetic parameters of Na(+) transport were determined from short
      circuit currents after fast release of ATP from its caged precursor. The falling
      phase of the current transients could be fitted by a single exponential with the
      time constant, tau (2). Its temperature dependence allowed an estimation of the
      activation energy of the rate-limiting reaction step, the conformation transition
      E(1)/E(2). Choline iodide and bromide caused a decrease of the activation energy
      as well as the overall rate of the process expressed as the pre-exponential
      factor A of the Arrhenius equation. If choline iodide or bromide were present on
      the cytoplasmic and extracellular sides of the protein, the temperature dependent
      changes were more pronounced than when present on the cytoplasmic side only.
      These results can be explained by an effect of the anions on water structure on
      the extracellular surface of the protein, where a deep access channel connects
      the ion-binding sites with the solution. Chloride ions also caused a deceleration
      of the electrogenic transport, however, in contrast to iodide or bromide, they
      did not affect the activation energy, and were more effective when added on the
      cytoplasmic side. This effect can be explained by asymmetric screening of the
      negative surface charges which leads to a transmembrane electric potential that
      modifies the ion transfer.

PMID- 16292646
TI  - Characterization of Bordetella pertussis growing as biofilm by chemical analysis
      and FT-IR spectroscopy.
AB  - Although Bordetella pertussis, the etiologic agent of whooping cough, adheres and
      grows on the ciliated epithelium of the respiratory tract, it has been
      extensively studied only in liquid cultures. In this work, the phenotypic
      expression of B. pertussis in biofilm growth is described as a first
      approximation of events that may occur in the colonization of the host. The
      biofilm developed on polypropylene beads was monitored by chemical methods and
      Fourier transform infrared (FT-IR) spectroscopy. Analysis of cell envelopes
      revealed minimal differences in outer membrane protein (OMP) pattern and no
      variation of lipopolysaccharide (LPS) expression in biofilm compared with
      planktonically grown cells. Sessile cells exhibited a 2.4- to 3.0-fold higher
      carbohydrate/protein ratio compared with different types of planktonic cells. A
      1.8-fold increased polysaccharide content with significantly increased
      hydrophilic characteristics was observed. FT-IR spectra of the biofilm cells
      showed higher intensity in the absorption bands assigned to polysaccharides
      (1,200-900 cm(-1) region) and vibrational modes of carboxylate groups (1,627,
      1,405, and 1,373 cm(-1)) compared with the spectra of planktonic cells. In the
      biofilm matrix, uronic-acid-containing polysaccharides, proteins, and LPS were
      detected. The production of extracellular carbohydrates during biofilm growth was
      not associated with changes in the specific growth rate, growth phase, or oxygen
      limitation. It could represent an additional virulence factor that may help B.
      pertussis to evade host defenses.

PMID- 16292647
TI  - Co-production of caffeic acid and p-hydroxybenzoic acid from p-coumaric acid by
      Streptomyces caeruleus MTCC 6638.
AB  - In a culture medium of Streptomyces caeruleus MTCC 6638 grown with p-coumaric
      acid (5 mM) as the sole source of carbon, co-production of caffeic acid and p
      hydroxybenzoic acid was observed. Both caffeic acid and p-hydroxybenzoic acid are
      important phenolic compounds with pharmaceutical importance. These biotransformed
      products were identified by high-performance liquid chromatography and
      electrospray ionization mass spectrometry. Obtained data suggest that p-coumaric
      acid was possibly utilized by two different routes, resulting in the formation of
      a hydroxycinnamate and a hydroxybenzoate compound. However, higher concentration
      of p-coumaric acid (10 mM) favoured caffeic acid formation. Addition of 5 mM p
      coumaric acid into S. caeruleus cultures pre-grown on minimal medium with 1.0 g/l
      glucose resulted in the production of 65 mg/l caffeic acid. Furthermore, S.
      caeruleus cells were able to produce the maximum amount of caffeic acid when pre
      grown on nutrient broth for 16 h. Under this condition, the addition of 5 mM p
      coumaric acid was sufficient for the S. caeruleus culture to produce 150 mg/l
      caffeic acid, with a molar yield of 16.6% after 96 h of incubation.

PMID- 16292648
TI  - Synthesis of enantiopure (5R)-hydroxyhexane-2-one with immobilised whole cells of
      Lactobacillus kefiri.
AB  - Whole-cell reduction of (2,5)-hexanedione to yield highly enantiopure (5R)
      hydroxyhexane-2-one (enantiomeric excess >99%) with Lactobacillus kefiri DSM
      20587 was investigated. Cell immobilisation with sodium cellulose sulphate was
      chosen as the most suitable encapsulation matrix, giving an immobilisation yield
      of 40%. Despite the lowered biocatalytic activity from cell immobilisation, the
      bioreduction process was vastly improved with the help of reaction engineering
      techniques (batch to a plug flow reactor set-up). High selectivity (95%) and
      space-time yield (87 g L(-1) day(-1)) were achieved in the plug flow reactor. The
      biocatalyst remained active (68% residual activity) after 6 days of operation.

PMID- 16292649
TI  - Diagnostic accuracy of non-invasive 64-slice CT coronary angiography in patients
      with stable angina pectoris.
AB  - Multislice computed tomography (CT) is an emerging technique for the non-invasive
      detection of coronary stenoses. While the diagnostic accuracy of 4-slice scanners
      was limited, 16-slice CT imagers showed promising results due to increased
      temporal and spatial resolution. These technical advances prompted us to evaluate
      the diagnostic performance of 64-slice CT coronary angiography in the detection
      of significant stenoses (defined as > or = 50% luminal diameter reduction) versus
      invasive quantitative coronary angiography (QCA). Thirty-five patients with
      stable angina pectoris underwent CT coronary angiography performed with a 64
      slice scanner (gantry rotation time 330 ms, individual detector width 0.6 mm)
      prior to conventional coronary angiography. Patients with heart rates >70
      beats/min received 100 mg metoprolol orally. One hundred millilitres of contrast
      agent with an iodine concentration of 400 mgl/ml were injected at a rate of 5
      ml/s into the antecubital vein. The CT scan was triggered with the bolus tracking
      technique. The sensitivity, specificity and the positive and negative predictive
      values of 64-slice CT were 99%, 96%, 78% and 99%, respectively, on a per-segment
      basis. The values obtained on a per-patient basis were 100%, 90%, 96% and 100%,
      respectively. When referral to catheterisation is questionable, CT coronary
      angiography may identify subjects with normal angiograms and consistently
      decrease the number of unnecessary invasive procedures.

PMID- 16292651
TI  - Altered renin-angiotensin system gene expression causes renal hypoplasia in the
      rats with nitrofen-induced diaphragmatic hernia.
AB  - The association between renal hypoplasia and pulmonary hypoplasia in congenital
      diaphragmatic hernia (CDH) has become recently appreciated. However, the
      underlying mechanisms responsible for this association are still unknown. Renin
      angiotensin system (RAS) plays an important role in renal and somatic growth,
      angiogenesis and reproduction. We hypothesized that abnormal expression of RAS
      components may be responsible for renal hypoplasia in CDH. We therefore designed
      this study to examine the gene expression of main components of RAS in the kidney
      of nitrofen-induced CDH in the rat. Pregnant rats were exposed to either olive
      oil or 100 mg of nitrofen on day 9.5 of gestation. Foetuses were recovered at
      term and divided into three groups: control (n=8), nitrofen without CDH (n=8) and
      CDH (n=8). Reverse transcription polymerase chain reaction was performed to
      evaluate the relative amount of angiotensinogen (AGT), angiotensin II type 1
      receptor with 1a and 1b subtypes (AT(1a)R and AT(1b)R), angiotensin II type 2
      receptor (AT(2)R), angiotensin-converting enzyme (ACE) and renin expression in
      the kidney. AT(1a)R, AT(1b)R, AT(2)R, AGT and renin levels were significantly
      decreased in the kidney of CDH rats compared with controls. We did not find a
      significant difference in ACE between CDH animals and controls. Our data show
      that the downregulation of RAS may play an important role in the pathogenesis of
      renal hypoplasia in the nitrofen-induced CDH.

PMID- 16292650
TI  - ANG II-induced attenuation of duck salt gland secretion does not depend upon the
      release of adrenal catecholamines.
AB  - Pekin ducks (Anas platyrhynchos) were bilaterally adrenalectomized (ADX) using a
      two-stage procedure and given daily i.m. injections of 1 mg kg bw(-1) of
      dexamethasone (DEXA), a steroid lacking mineralocorticoid activity, and 0.9%
      saline drinking water ad libitum to counterbalance renal losses of salt and
      water. Mean arterial blood pressure (mmHg) fell from 161+/- 3.7 (intact controls)
      to 116 +/- 6.9 (bilateral ADX+DEXA), a decrease of 27%, but heart rates (HR) were
      unchanged. The nasal salt glands were fully active after ADX + DEXA. Rates of
      fluid secretion and electrolyte and osmolal concentrations were unchanged.
      Secretion stopped, then rebounded several minutes later if ADX + DEXA ducks were
      injected i.v. with 1 microg of [Asn(1),Val(5)]-angiotensin II (ANG II) kg bw(-1)
      which showed that attenuation was not adrenal catecholamine-dependent.

PMID- 16292652
TI  - Sex and congenital diaphragmatic hernia.
AB  - BACKGROUND AND PURPOSE: Human studies note sex reversal syndromes and sex
      difference(s) in the incidence of congenital diaphragmatic hernia (CDH).
      Epidemiology surveys record a higher incidence of CDH in females, whilst other
      reports cite a higher frequency in males. Nitrofen, a teratogen, produces
      experimental CDH. This agent is speculated to interfere with retinoid acid
      steroid signalling pathways and may also be linked with sexual differentiation.
      This study was designed therefore to test the hypothesis that nitrofen may
      influence sexual phenotype and frequency of CDH. METHODS: Time mated Sprague
      Dawley rats were dosed with nitrofen at day 9.5 to generate predominantly left
      sided CDH. Fetuses were delivered by caesarean section on days 20 or 21 of
      gestation (term=day 22). External genitalia were examined to define external
      genital phenotype. The abdominal cavity was opened and the genito-urinary system
      carefully examined. The internal genital organs were assigned a phenotype and
      findings correlated with external appearances. The diaphragm of each fetus was
      studied for the absence or presence of CDH and the laterality of defect recorded.
      Controls (non nitrofen fed) were used for all comparative analysis. RESULTS:
      Control (n=600) and nitrofen exposed offspring (n=504) had equal frequencies of
      males and females. CDH occurred with similar incidence in male and female
      nitrofen treated pups. In all nitrofen exposed fetuses and normal controls,
      internal and external genitalia concorded without evidence of significant genital
      tract malformations or intersex states. CONCLUSIONS: Prenatal nitrofen exposure
      is not associated with significant gender differences (or prenatal loss) in the
      risk of CDH. Genital tract malformations do not appear to accompany CDH in the
      nitrofen model.

PMID- 16292654
TI  - Perforated appendicitis presenting as appendicoumbilical fistula.
AB  - Perforated appendicitis is one of the most common diagnoses treated by pediatric
      surgeons. Although rare, a perforated appendix can present with a cutaneous
      fistula. Here we present the second reported case of perforated appendicitis
      presenting as an appendicoumbilical fistula.

PMID- 16292653
TI  - TNF-alpha is a mediator of the anti-inflammatory response in a human neonatal
      model of the non-septic shock syndrome.
AB  - The anti-inflammatory/immunoparalytic phase of the systemic inflammatory response
      syndrome (SIRS) following major insult (surgery, thermal/traumatic injury) is of
      major clinical importance in the neonate, during which the risk of infection is
      particularly great. Here, the mechanisms by which TNF-alpha production is
      suppressed in response to infection are largely unknown. We questioned whether
      TNF-alpha itself could be a critical mediator of this suppression. Monocytes,
      isolated from cord blood (n=3), were treated with LPS (100 ng/ml), TNF-alpha (10
      ng/ml, +/- anti-TNF-alpha antibody) for 18 and 36 h. Cells were then restimulated
      with LPS (Gram -ve) or Pam-3-Cys (Gram +ve) for 24 h. This was also done in the
      presence of selective inhibitors of MAP kinases p38, MEK and JNK. TNF-alpha, IL
      6, IL-10 and IL-8 were quantified by ELISA CD86 and HLA-DR expression were
      determined flow cytometrically. Cells stimulated with LPS for 24 h produced TNF
      alpha (282 pg/ml), IL-10 (1,236 pg/ml), IL-6 (2,694 pg/ml) and IL-8 (2,144
      pg/ml). In cells pre-exposed to TNF-alpha for 36 h, there was a significant
      suppression in TNF-alpha and IL-6 levels (9 and 221 pg/ml, respectively) (P<0.05)
      with minimal impact on IL-10 (1,206 pg/ml) and IL-8 levels (1,886 pg/ml). A
      similar effect was seen with Pam-3-Cys with a tenfold decrease in levels of TNF
      alpha and IL-6 (86-->8.5 pg/ml and 458-->46 pg/ml, respectively) with no effect
      on IL-10 and IL-8 levels. Anti-TNF-alpha antibody negated this effect. Inhibition
      of p38 kinase reversed the TNF-alpha effect. Inhibition of the JNK and MEK
      kinases had no effect. A reduction in the expression of CD86 and HLA-DR was
      observed. This ex-vivo model of non-septic SIRS demonstrates that TNF-alpha,
      released during a major insult, can suppress subsequent monocyte responses to
      bacterial agents through p38 MAP kinase, making it a potential therapeutic
      target.

PMID- 16292655
TI  - Cutaneous distribution and localization of dyes affected by vehicles all with
      different lipophilicity.
AB  - The penetration of topically applied substances into the stratum corneum (SC)
      depends on several factors, e.g., the physicochemical properties of the vehicle
      used for application. The penetration of highly hydrophilic and lipophilic dyes
      into the skin was studied using a pure oil (o) or water (w) for the application
      compared to an o/w emulsion. The penetration and localization of both dyes, the
      lipophilic curcumin and the hydrophilic Patent blue V, was investigated in vivo
      using the method of tape stripping and microscopy. In addition, histological
      sections of biopsies, removed from porcine ear skin were studied using
      microscopy. Differences in the distribution and the localization of both dyes
      within the SC were observed. These differences depend on the physicochemical
      properties of both the vehicles and the dyes. The vehicle appears to affect, in
      particular, the pathways of penetration.

PMID- 16292656
TI  - GDx-VCC performance in discriminating normal from glaucomatous eyes with early
      visual field loss.
AB  - BACKGROUND: To evaluate the ability of scanning laser polarimetry with variable
      corneal compensation (GDx-VCC) in separating healthy from glaucomatous patients
      with early visual field (VF) loss. METHODS: Sixty-two healthy and 48 glaucomatous
      age-matched patients with early glaucoma [mean deviation (MD): -1.74dB +/-1.69]
      underwent complete ophthalmological evaluation, automated achromatic perimetry
      (AAP) and retinal nerve fiber layer (RNFL) measurement with GDx-VCC. One randomly
      selected eye from each subject was considered. Glaucomatous VF defects had either
      Glaucoma Hemifield Test (GHT) outside normal limits or pattern standard deviation
      (PSD) outside 95% confidence limits. Mean (+/-SD) MD, PSD and GDx-VCC parameters
      in the two groups were compared by t-test. For each GDx-VCC parameter, area under
      receiver operating characteristics (AUROC) curve and sensitivity at predetermined
      specificity > or =80% and > or =95% were calculated. Moreover, the parameter with
      largest AUROC was evaluated by likelihood ratios (LRs). RESULTS: Mean values for
      MD, PSD and ten of 14 GDx-VCC parameters were significantly different between the
      two groups (P<0.001). The three parameters with largest AUROCs were the nerve
      fiber indicator (NFI) (0.870), superior average (0.817) and normalized superior
      area (0.816) (P=0.08 for differences between AUROCs). NFI displayed sensitivity
      values of 80.2% and 60.4% for specificity > or =80% and > or =95%, respectively.
      At NFI cutoff value of 30, positive LR was 34.9 (95% CI: 4.9-247.6) and negative
      LR was 0.45 (95% CI: 0.32-0.61). Interval LRs showed large effect on post-test
      probability for NFI values < or =18 or > or =31. CONCLUSIONS: In our sample of
      eyes with early VF loss, GDx-VCC showed moderate-to-good discriminating ability.
      Among the best performing parameters, NFI had the largest AUROC, but several
      glaucomatous eyes (21, 43.8%) had NFI <30. This suggests that algorithm for NFI
      calculation requires some refinement when eyes with early VF loss are evaluated.

PMID- 16292657
TI  - Nitric oxide synthase in human skeletal muscles related to defined fibre types.
AB  - Skeletal muscle functions regulated by NO are now firmly established. However,
      the knowledge about the NO synthase (NOS) expression related to a defined fibre
      type in human skeletal muscles necessitates further clarification. To address
      this issue, we examined localization of NOS isoforms I, II and III, in human
      skeletal muscles employing immunocytochemical labeling with tyramide signal
      amplification complemented with enzyme histochemistry and Western blotting. The
      NOS immunoreactivity was related to fibre types of different classification
      systems: physiological classification into slow and fast, ATPase classification
      into I, IIA, IIAX, IIX, and physiological-metabolic classification into slow
      oxidative (SO), fast-oxidative glycolytic (FOG) and fast-glycolytic (FG). We
      found a correlation of NOS I-III immunoreactivity to metabolic defined fibre
      types with strong expression in FOG fibres. This implies that NO as modulator of
      muscle function is involved in oxidative metabolism in connection with fast force
      development, which only occurs in FOG fibres. The NOS expression showed no
      correlation to ATPase fibre subtypes due to the metabolic heterogeneity of ATPase
      fibre types. Healthy and affected vastus medialis muscles after anterior cruciate
      ligament rupture revealed similar NOS expression level as shown by Western
      blotting with, however, different expression patterns related to the fibre types
      in affected muscles. This suggests an altered modulation of force development in
      the fibres of diseased muscles.

PMID- 16292659
TI  - Schema-based learning of adaptable and flexible prey-catching in anurans I. The
      basic architecture.
AB  - A motor action often involves the coordination of several motor synergies and
      requires flexible adjustment of the ongoing execution based on feedback signals.
      To elucidate the neural mechanisms underlying the construction and selection of
      motor synergies, we study prey-capture in anurans. Experimental data demonstrate
      the intricate interaction between different motor synergies, including the
      interplay of their afferent feedback signals (Weerasuriya 1991; Anderson and
      Nishikawa 1996). Such data provide insights for the general issues concerning two
      way information flow between sensory centers, motor circuits and periphery in
      motor coordination. We show how different afferent feedback signals about the
      status of the different components of the motor apparatus play a critical role in
      motor control as well as in learning. This paper, along with its companion paper,
      extend the model by Liaw et al. (1994) by integrating a number of different motor
      pattern generators, different types of afferent feedback, as well as the
      corresponding control structure within an adaptive framework we call Schema-Based
      Learning. We develop a model of the different MPGs involved in prey-catching as a
      vehicle to investigate the following questions: What are the characteristic
      features of the activity of a single muscle? How can these features be controlled
      by the premotor circuit? What are the strategies employed to generate and
      synchronize motor synergies? What is the role of afferent feedback in shaping the
      activity of a MPG? How can several MPGs share the same underlying circuitry and
      yet give rise to different motor patterns under different input conditions? In
      the companion paper we also extend the model by incorporating learning components
      that give rise to more flexible, adaptable and robust behaviors. To show these
      aspects we incorporate studies on experiments on lesions and the learning
      processes that allow the animal to recover its proper functioning.

PMID- 16292658
TI  - An in vitro model for studying vascular injury after laser microdissection.
AB  - We have developed an in vitro model for studying vascular injury. After 7-10 days
      in a three-dimensional collagen gel culture, capillary-like tubes were formed in
      the collagen gels. We injured these capillary-like tubes with a laser
      microdissection system or a scrape method with razors and then examined the
      collagen gel culture by phase contrast and electron microscopy. After laser
      injury, profuse necrotic cells were observed around the injured capillary-like
      tubes and within the tubular lumen compared to the razor injury. We then isolated
      total RNA from these cultures and prepared cDNA for investigations by
      quantitative real-time reverse transcription polymerase chain reaction (RT-PCR).
      Quantitative real time RT-PCR revealed the up-regulation of transcription factor
      early growth response-1 (Egr-1) after both laser and razor injury, accompanied by
      the up-regulation of fibroblast growth factor-2 (FGF-2), a proangiogenic factor
      downstream of Egr-1. The effective laser energy is concentrated on the minute
      focal spot only. These methods provide a useful in vitro model for studying
      vascular injury.

PMID- 16292662
TI  - Small-cell variant of renal oncocytoma with dominating solid growth pattern: a
      potential diagnostic pitfall.

PMID- 16292660
TI  - Differential accumulation of monolignol-derived compounds in elicited flax (Linum
      usitatissimum) cell suspension cultures.
AB  - Lignin and lignans share monolignols as common precursors and are both
      potentially involved in plant defence against pathogens. In this study, we
      investigated the effects of fungal elicitors on lignin and lignan metabolism in
      flax (Linum usitatissimum) cell suspensions. Cell suspension cultures of flax
      were treated with elicitor preparations made from mycelium extracts of Botrytis
      cinerea, Phoma exigua and Fusarium oxysporum F ssp lini. Elicitors induced a
      rapid stimulation of the monolignol pathway, as confirmed by the increase in PAL
      (phenylalanine ammonia-lyase, EC 4.1.3.5), CCR (cinnamoyl-CoA reductase EC
      1.2.1.44) and CAD (cinnamyl alcohol dehydrogenase EC 1.1.1.195) gene expression
      and PAL activity. At the same time, CCR activity only increased significantly in
      F. oxysporum-treated cells 24 h post elicitation. On the other hand, CAD activity
      measured for coniferyl alcohol formation was transiently decreased but a
      substrate-specific activation of CAD activity was observed in F. oxysporum
      treated cells when using sinapyl alcohol as substrate. The accumulation of
      monolignol-derived products varied according to the elicitor used. B. cinerea or
      P. exigua-elicited cell cultures were characterised by a reinforcement of the
      cell wall by a deposit of 8-O-4'-linked non-condensed lignin structures and
      phenolic monomers, while at the same time no stimulation of 8-8'-linked lignan or
      8-5'-linked phenylcoumaran lignan accumulation was observed. Additionally,
      elicitation of cell cultures with F. oxysporum extracts even triggered a strong
      incorporation of monolignols in the non condensed labile ether-linked lignin
      fraction concomitantly with a decrease in lignan and phenylcoumaran lignan
      accumulation. Several hypotheses are proposed to explain the putative role of
      these compounds in the defence response of flax cells against pathogens.

PMID- 16292661
TI  - How does glutamine synthetase activity determine plant tolerance to ammonium?
AB  - The wide range of plant responses to ammonium nutrition can be used to study the
      way ammonium interferes with plant metabolism and to assess some characteristics
      related with ammonium tolerance by plants. In this work we investigated the
      hypothesis of plant tolerance to ammonium being related with the plants' capacity
      to maintain high levels of inorganic nitrogen assimilation in the roots. Plants
      of several species (Spinacia oleracea L., Lycopersicon esculentum L., Lactuca
      sativa L., Pisum sativum L. and Lupinus albus L.) were grown in the presence of
      distinct concentrations (0.5, 1.5, 3 and 6 mM) of nitrate and ammonium. The
      relative contributions of the activity of the key enzymes glutamine synthetase
      (GS; under light and dark conditions) and glutamate dehydrogenase (GDH) were
      determined. The main plant organs of nitrogen assimilation (root or shoot) to
      plant tolerance to ammonium were assessed. The results show that only plants that
      are able to maintain high levels of GS activity in the dark (either in leaves or
      in roots) and high root GDH activities accumulate equal amounts of biomass
      independently of the nitrogen source available to the root medium and thus are
      ammonium tolerant. Plant species with high GS activities in the dark coincide
      with those displaying a high capacity for nitrogen metabolism in the roots.
      Therefore, the main location of nitrogen metabolism (shoots or roots) and the
      levels of GS activity in the dark are an important strategy for plant ammonium
      tolerance. The relative contribution of each of these parameters to species
      tolerance to ammonium is assessed. The efficient sequestration of ammonium in
      roots, presumably in the vacuoles, is considered as an additional mechanism
      contributing to plant tolerance to ammonium nutrition.

PMID- 16292663
TI  - In situ and in vitro colonization of Cathaya argyrophylla (Pinaceae) by
      ectomycorrhizal fungi.
AB  - Cathaya argyrophylla, a critically endangered conifer, is found to grow at four
      isolated areas located in subtropical mountains of China. To examine the
      involvement and usefulness of mycorrhizas for sustaining the population of this
      tree, we compared the root system, morphology, and structure of mycorrhizal roots
      of C. argyrophylla, which were collected from a natural stand and an artificial
      stand, each grown at a different location. More mycorrhizal roots were found for
      trees from an artificial stand. The presence of extramatrical mycelium, mantle,
      and Hartig net revealed that C. argyrophylla formed an ectomycorrhizal
      association in both sampling sites. Starch granules were found in mycorrhizal
      roots collected only from a natural stand. The aseptic synthesis of C.
      argyrophylla and Cenococcum geophilum was established for the first time in
      vitro. Typical ectomycorrhizas formed on seedlings on RM medium containing 0.1
      g/l glucose, 5 weeks after inoculation. By light microscopy, the synthesized
      mycorrhizas showed a thin mantle from which emanated extramatrical hyphae and
      highly branched Hartig net. A simple, rapid, and convenient mycorrhiza synthesis
      system was developed, which facilitates further studies on ectomycorrhizal
      development of C. argyrophylla.

PMID- 16292664
TI  - Preoperative chemoradiation for rectal cancer causes prolonged pudendal nerve
      terminal motor latency.
AB  - PURPOSE: A worsened anorectal function after chemoradiation for high-risk rectal
      cancer is often attributed to radiation damage of the anorectum and pelvic floor.
      Its impact on pudendal nerve function is unclear. This prospective study
      evaluated the short-term effect of preoperative combined chemoradiation on
      anorectal physiologic and pudendal nerve function. METHODS: Sixty-six patients
      (39 men, 27 women) with localized resectable (T3, T4, or N1) rectal cancer were
      included in the study. All patients received 45 Gy (1.8 Gy/day in 25 fractions)
      over five weeks, plus 5-fluorouracil (350 mg/m2/day) and leucovorin (20
      mg/m2/day) concurrently on days 1 to 5 and 29 to 33. Patients who had rectal
      cancer with a distal margin within 6 cm of the anal verge had the anus included
      in the field of radiotherapy (Group A, n = 26). Patients who had rectal cancer
      with a distal margin 6 to 12 cm from the anal verge had shielding of the anus
      during radiotherapy (Group B, n = 40). The Wexner continence score, anorectal
      manometry and pudendal nerve terminal motor latency were assessed at baseline and
      four weeks after completion of chemoradiation. RESULTS: The median Wexner score
      deteriorated significantly (P < 0.0001) from 0 to 2.5 for both Groups A (range, 0
      8) and B (range, 0-14). The maximum resting anal pressures were unchanged after
      chemoradiation. The maximum squeeze anal pressures were reduced (mean = 166.5
      157.5 mmHg) after chemoradiation. This change was similar in both Groups A and B.
      Eighteen patients (Group A = 7, Group B = 11) developed prolonged pudendal nerve
      terminal motor latency after chemoradiation. These 18 patients similarly had a
      worsened median Wexner continence score (range, 0-3) and maximum squeeze anal
      pressures (mean = 165.5-144 mmHg). The results obtained were independent of tumor
      response to chemoradiation. CONCLUSIONS: Preoperative chemoradiation for rectal
      cancer carries a significant risk of pudendal neuropathy, which might contribute
      to the incidence of fecal incontinence after restorative proctectomy for rectal
      cancer.

PMID- 16292666
TI  - Quantification of outpatient management and hospitalization of patients with high
      risk myelodysplastic syndrome treated with low-dose decitabine.
AB  - Intravenous low-dose 5-aza-2'-deoxycytidine (decitabine) in patients with
      advanced myelodysplastic syndrome (MDS) yields an approximately 50% overall
      response rate, including 20-25% complete remission. Decitabine-treated MDS
      patients can be managed as outpatients after completion of a 3-day infusion
      schedule. In-hospital nights (IHNs), overall survival (OS), and remaining life
      spent in hospital were evaluated and compared to a matched control group
      receiving different standard treatments. Between July 1992 and September 2001, 99
      high-risk MDS patients, median age 70 years (range 49-86), were treated with low
      dose decitabine. Durations of all hospitalizations were recorded. For matched
      pair analysis, 44 decitabine-treated patients were matched to 44 MDS patients
      according to International Prognostic Scoring System classification, period of
      diagnosis, age, French-American-British classification, and gender. Median number
      of IHN across all patients was 56 and survival was 481 days, resulting in 84% of
      remaining life spent at home. In the matched-pair analysis, the median number of
      IHN was 57 in the decitabine group vs. 50 in the control group. Median survival
      was 400 vs. 371 days for the decitabine and control groups, respectively. Median
      number of remaining life spent at home was identical (83% for both groups).
      Matched patients who received only best supportive care (n=12) had a shorter
      median survival than the decitabine patients (234 vs. 400 days), and the
      proportion of remaining life spent at home was slightly greater (82 vs. 77%).
      Interestingly, matched patients with induction therapy showed comparable IHN, OS,
      and remaining life spent at home. In conclusion, high-risk MDS patients treated
      with low-dose decitabine have better survival, and spend comparable time in
      hospital than patients treated with supportive treatment.

PMID- 16292665
TI  - Human low-density lipoprotein receptor gene and its regulation.
AB  - The low-density lipoprotein (LDL) receptor is a transmembrane glycoprotein that
      mediates the binding and endocytosis of lipoproteins containing apolipoprotein B
      and E, especially the cholesterol-rich LDL. Mutations in the LDL receptor gene
      can produce dysfunctional LDL receptors and cause familial hypercholesterolemia.
      The expression of the LDL receptor gene is under an intriguing regulation by
      sterol and nonsterol mediators either at the transcriptional level or at the
      posttranscriptional level, both of which are linked to cell signaling pathways.
      Upregulation of liver LDL receptor expression is effective in treating
      hypercholesterolemia. In this review, we focus on the latest progress on the
      mechanisms and regulation of the LDL receptor gene expression.

PMID- 16292667
TI  - Stress-induced transcription of the endoplasmic reticulum oxidoreductin gene ERO1
      in the yeast Saccharomyces cerevisiae.
AB  - Gene transcription changes dramatically in response to various stresses. This
      event is an obligatory step for adaptation of cells to certain environments.
      Endoplasmic reticulum (ER) oxidoreductin encoded by the ERO1 gene of the yeast
      Saccharomyces cerevisiae is essential for the formation of protein disulfide
      bonds in the ER and for cell viability. We show that transcription of ERO1 is
      regulated by two transcriptional activators in response to different stresses. In
      the unfolded protein response induced by the reductant dithiothreitol,
      transcription factor Hac1 activates ERO1 transcription through a sequence that
      diverges from the consensus Hac1-binding sequence. Heat shock transcription
      factor Hsf1 activates ERO1 in response to heat, ethanol, and oxidative stresses.
      Using cells containing mutations in the Hac1- and Hsf1-binding sequences of the
      chromosomal ERO1 promoter, we demonstrate that Hac1-regulated transcription of
      ERO1 confers resistance to dithiothreitol. Although mutations in the Hsf1-binding
      sequences do not affect the sensitivity of cells to heat, ethanol, or oxidative
      stresses, both the Hac1- and Hsf1-regulated pathways are critical for normal
      growth under complex stress conditions.

PMID- 16292668
TI  - Survey of resistance gene analogs in Solanum caripense, a relative of potato and
      tomato, and update on R gene genealogy.
AB  - The resistance (R) proteins of the TIR- and non-TIR (or CC-) superfamilies
      possess a nucleotide binding site (NBS) domain. Within an R gene, the NBS is the
      region of highest conservation, suggesting an essential role in triggering R
      protein activity. We compared the NBS domain of functional R genes and resistance
      gene analogs (RGA) amplified from S. caripense genomic DNA via PCR using specific
      and degenerate primers with its counterpart from other plants. An overall high
      degree of sequence conservation was apparent throughout the P-loop, kinase-2 and
      kinase-3a motifs of NBS fragments from all plants. Within the non-TIR class of R
      genes a prominent sub-class similar to the potato R1 gene conferring resistance
      to late blight, was detected. All non-TIR-R1-like R gene fragments that were
      sequenced possessed an intact open reading frame, whereas 22% of all non-TIR-non
      R1-like fragments and 59% of all TIR-NBS RGA fragments had an interrupted reading
      frame or contained transposon-specific sequence. The non-TIR-R1-like fragments
      had high similarity to Solanaceae R genes and low similarity to RGAs of other
      plant species including A. thaliana and the cereals. It is concluded that
      appearance of the non-TIR-R1-like NBS domain represents a relatively recent
      evolutionary development.

PMID- 16292669
TI  - A single-crystal ENDOR and density functional theory study of the oxidized states
      of the [NiFe] hydrogenase from Desulfovibrio vulgaris Miyazaki F.
AB  - The catalytic center of the [NiFe] hydrogenase of Desulfovibrio vulgaris Miyazaki
      F in the oxidized states was investigated by electron paramagnetic resonance and
      electron-nuclear double resonance spectroscopy applied to single crystals of the
      enzyme. The experimental results were compared with density functional theory
      (DFT) calculations. For the Ni-B state, three hyperfine tensors could be
      determined. Two tensors have large isotropic hyperfine coupling constants and are
      assigned to the beta-CH2 protons of the Cys-549 that provides one of the bridging
      sulfur ligands between Ni and Fe in the active center. From a comparison of the
      orientation of the third hyperfine tensor with the tensor obtained from DFT
      calculations an OH- bridging ligand has been identified in the Ni-B state. For
      the Ni-A state broader signals were observed. The signals of the third proton, as
      observed for the "ready" state Ni-B, were not observed at the same spectral
      position for Ni-A, confirming a structural difference involving the bridging
      ligand in the "unready" state of the enzyme.

PMID- 16292670
TI  - Stability and fluctuations of amide hydrogen bonds in a bacterial cytochrome c: a
      molecular dynamics study.
AB  - Molecular dynamics (MD) simulations on a bacterial cytochrome c were performed to
      investigate the lifetime and fluctuations of backbone hydrogen bonds and to
      correlate these data with protection factors for hydrogen exchange measured by
      NMR spectroscopy (Bartalesi et al. in Biochemistry, 42:10923-10930, 2003). The MD
      simulations provide a consistent pattern in that long lifetimes of hydrogen bonds
      go along with small amplitude fluctuations. In agreement with experiments,
      differences in stability were found with a rather flexible N-terminal segment as
      compared with a more rigid C-terminal part. Protection factors of backbone
      hydrogen exchange correlate strongly with the number of contacts but also with
      hydrogen-bond occupancy, hydrogen-bond survival times, as well as the inverse of
      fluctuations of backbone atoms and hydrogen-bond lengths derived from MD
      simulation data. We observed a conformational transition in the C-terminal loop,
      and significant motion in the N-terminal loop, which can be interpreted as being
      the structural units involved in the onset of the protein unfolding process in
      agreement with experimental evidence on mitochondrial cytochrome c.

PMID- 16292671
TI  - Segregation at the SCN resistance locus rhg1 in soybean is distorted by an
      association between the resistance allele and reduced field emergence.
AB  - Segregation distortion has been reported repeatedly in soybean (Glycine max [L.]
      Merr.) inbred line populations segregating for the soybean cyst nematode (SCN)
      (Heterodera glycines Ichinohe) resistance gene rhg1. In each reported case, the
      frequency of the SCN resistance allele at the rhg1 locus was lower than expected.
      Segregation distortion was studied in 51 F4 populations by counting the number of
      plants predicted to be homozygous resistant, susceptible, and heterozygous for
      rhg1 based on the genetic markers Satt309, CTA, or TMA5. Significant (P<0.05)
      segregation distortion was observed in 44 out of the 51 F4 populations. When the
      heterozygotes were ignored, there were significantly fewer homozygous-resistant
      plants than expected in 33 populations. To study whether differential field
      emergence was a cause of the segregation distortion, three near isogenic line
      (NIL) populations segregating at the rhg1 locus for SCN resistance from plant
      introduction 88788 were tested. Population sizes ranged from 32 to 44 NILs and
      emergence was determined in field experiments in three environments. In each
      population, SCN-resistant NILs had significantly (P<0.05) less field emergence
      than susceptible NILs. In the population with the greatest effect, field
      emergence of resistant NILs was 6% less than susceptible NILs, with the entire
      population having an average emergence rate of 46%. Equations were derived to
      describe the effect of selection on segregation ratios over generations of
      population development and the observed emergence rates were transformed into
      fitness factors. Depending on assumptions of gene action, it was predicted from
      these fitness factors that segregation distortions were in the range of those
      reported previously for the rhg1 locus and were similar to what was observed on
      average across the 51 F4 populations. While other factors might also be involved,
      the results suggest that reduced field emergence associated with the SCN
      resistance allele contributes to previously reported segregation distortion at
      the rhg1 locus.

PMID- 16292672
TI  - Variants of the SFTPA1 and SFTPA2 genes and susceptibility to tuberculosis in
      Ethiopia.
AB  - Lungs are the central organ affected and targeted by Mycobacterium tuberculosis
      and immune processes in the lung are of critical importance in the pathogenesis
      of tuberculosis. A major lung defense against invading pathogens is provided by
      surfactant protein A, a multi-chain protein encoded by the SFTPA1 and SFTPA2
      genes. Here, we investigated polymorphisms in the SFTPA1 and SFTPA2 genes for
      association with tuberculosis in 181 Ethiopian families comprising 226
      tuberculosis cases. Four polymorphisms, SFTPA1 307A, SFTPA1 776T, SFTPA2 355C,
      and SFTPA2 751C, were associated with tuberculosis (P=0.00008; P=0.019, P=0.029
      and P=0.042, respectively). Additional subgroup analysis in male, female and more
      severely affected patients provided evidence for SFTPA1/2-covariate interaction.
      Finally, out of five intragenic haplotypes identified in the SFTPA1 gene and nine
      identified in the SFTPA2 gene, 1A(3) was most significantly associated with
      tuberculosis susceptibility (P=0.026). These findings suggest that SFTPA1 and
      SFTPA2 modify the risk of tuberculosis susceptibility and that this risk is
      influenced by additional covariates.

PMID- 16292673
TI  - Human F7 sequence is split into three deep clades that are related to FVII plasma
      levels.
AB  - It is widely accepted that FVII levels are strongly, consistently, and
      independently related to cardiovascular risk. These levels are influenced by
      genetic and environmental factors. Among the genetic factors, only a limited
      number of polymorphisms in the F7 gene have been reported, and they explain only
      a small proportion of the genetic variability. Recently, we have accomplished the
      complete dissection of the F7 quantitative trait locus responsible for all of the
      genetic variability observed in FVII levels. Now, we present the thorough study
      of the haplotype organization of F7 DNA sequence variation among individuals and
      the evolutionary processes that produced this variation, by sequencing 15 kb of
      genomic DNA sequence from the F7 locus in 40 unrelated individual (80
      chromosomes) from the genetic analysis of idiopathic thrombophilia (GAIT) project
      as well as four non-human primate species. Our study revealed 49 polymorphisms,
      of which 39 SNPs were further considered. Genotyping of these DNA variations in
      the whole family-based GAIT sample helped resolve linkage phases, and a total of
      37 distinct haplotypes were identified.Tajima's D was significantly positive in
      this sample, suggesting balancing selection. This parameter was a reflection of
      the phylogenetic structure of F7 haplotype, which was deeply split into three
      well-supported clades or haplogroups, suggesting that functional differences
      among F7 variants do not depend on a few single-site variations. Moreover,
      haplogroup 2 was associated with high FVII levels and haplogroup 3 with low
      levels. In this study, we have for the first time established a clear relation
      between genotypic variability structure and phenotypic variability of a
      particular quantitative trait involved in a complex disease.

PMID- 16292674
TI  - Carbamide peroxide bleaching agents: effects on surface roughness of enamel,
      composite and porcelain.
AB  - This study examined the effect of 10 and 35% carbamide peroxide bleaching agents
      on the surface roughness of enamel, feldspathic porcelain, and microfilled and
      microhybrid composite resins. Standardized cylindrical specimens were prepared
      for restorative materials. Enamel samples were obtained from buccal and lingual
      surfaces of human molars. Samples from each substrate were divided in three
      subgroups (n=10), according to surface treatment: distilled water (control), and
      10 and 35% carbamide peroxide. The 10% agent was applied 3 h daily and the 35%
      agent was applied for 30 min/week, at 37 degrees C, during 21 days. Control
      samples remained stored in distilled water, at 37 degrees C. Roughness
      measurements (Ra, microm) were made at 24 h and repeated after 7, 14 and 21 days
      of exposure. Data were analyzed using ANOVA (split-plot design) and Tukey's test
      (5% significance level). Samples from control groups showed no significant
      alteration during all test periods, while for exposure to 10% agent, only the
      porcelain presented a rougher surface after 21 days (p<0.05). For the 35%
      product, roughness means significantly increased during the first and second
      weeks for enamel (p<0.05), and after 21 days for porcelain (p<0.05) and for the
      microhybrid composite (p<0.05). Microfilled samples showed no significant
      alteration throughout the 21-day period, regardless of the surface treatment.

PMID- 16292675
TI  - Syncope and head CT scans in the emergency department.
AB  - CONTEXT: Patients presenting with syncope to the emergency department (ED) of a
      community hospital were evaluated. AIM: The objective of this study is to examine
      the use and results of head computerized tomography (CT) scans in patients
      presenting with syncope to the ED of a community hospital. SETTINGS AND DESIGN: A
      retrospective chart review of patients presenting with syncope to the emergency
      room was conducted. METHODS AND MATERIALS: We reviewed the charts of patients who
      presented to the ED over a 6-month period with syncope. When performed, head CT
      scan findings were noted, and their relationship to the clinical presentation was
      examined. RESULTS: One hundred twenty-eight patients were identified. Forty-four
      patients had their head CT scans performed. In 1 patient, the CT scan showed
      evidence of infarction in the posterior circulation. In 19 patients, the head CT
      scan was normal. Twenty-four patients had abnormal findings unrelated to the ED
      presentation. CONCLUSIONS: Head CT scans were commonly used in our series of
      syncope patients. Abnormal findings pertinent to the syncope were observed in
      only 1 patient. A prospective study examining yield in a larger series of
      patients may help define the utility of this neuroimaging modality in syncope.

PMID- 16292676
TI  - Increased phosphoglucomutase activity suppresses the galactose growth defect
      associated with elevated levels of Ras signaling in S. cerevisiae.
AB  - The Ras proteins regulate many aspects of cell growth in the budding yeast,
      Saccharomyces cerevisiae, via the cAMP-dependent protein kinase (PKA). Here, we
      show that a RAS2(val19) mutant that exhibits elevated levels of Ras/PKA signaling
      activity is unable to grow on media with galactose as the sole source of carbon.
      This growth defect was due, at least in part, to a defect in the expression of
      genes, like GAL1, that encode enzymes needed for the metabolism of galactose.
      This growth defect was used as the basis for a genetic screen for dosage
      suppressors of the RAS2(val19) mutant. This screen identified two genes, PGM1 and
      PCM1, that encode proteins with phosphoglucomutase activity. This activity is
      responsible for converting the glucose-1-phosphate produced during the metabolism
      of galactose to glucose-6-phosphate, a precursor that can be metabolized via the
      glycolytic pathway. The over-expression of PGM1 was not able to suppress any
      other RAS2(val19) phenotype or the galactose growth defect associated with a
      gal1Delta mutant. Overall, these data suggest that the elevated levels of
      phosphoglucomutase activity allow for the more efficient utilization of the
      limiting levels of glucose-1-phosphate that are present in the RAS2(val19)
      mutant.

PMID- 16292677
TI  - The use of a recombinant baculovirus expressing a chitinase from the hard tick
      Haemaphysalis longicornis and its potential application as a bioacaricide for
      tick control.
AB  - Baculoviruses are specific insect pathogens used as selective biological
      insecticides on lepidopteran insects. We have tested a recombinant baculovirus
      expressing a chitinase gene for its efficacy as a tick bioacaricide. The
      recombinant Autographa californica multiple nuclear polyhedrosis virus expressing
      a chitinase enzyme (AcMNPV-CHT1) from the hard tick, Haemaphysalis longicornis,
      was constructed and found to have a novel bioacaricidal effect against ticks. The
      recombinant baculovirus was used to express the chitinase enzyme in Spodoptera
      frugiperda (Sf9) insect cells. Topical application of the supernatant harvested
      from the insect cell culture was found to cause mortality in nymphal ticks of H.
      longicornis. High temperature (>30 degrees C) and infrared radiation affected the
      chitinase enzyme activity and recombinant baculovirus infectivity by reducing the
      speed of tick killing by 60%. A mixture of recombinant virus and chitinase was
      found to kill ticks faster (p < 0.01) than pure chitinase and recombinant virus
      alone. Thus, the recombinant virus showed a synergistic effect with the foreign
      chitinase gene. In order to reduce the excessive use and cost of acaricides, it
      was found that a mixture of recombinant virus and flumethrin could halve the dose
      of the chemical acaricide used. These findings are important for the safe use of
      the recombinant virus expressing chitinase as a bioacaricide against ticks.

PMID- 16292679
TI  - Eccentric training of painful supraspinatus tendinosis.

PMID- 16292681
TI  - Operative treatment of deep chondral defects of the patella.

PMID- 16292678
TI  - Obtaining hyperimmune anti-Cryptosporidium parvum ovine colostrum. A study of the
      humoral immune response in immunized sheep.
AB  - Three ewes were immunized five times over a 2-month period prior to giving birth
      by intramuscular injection, oral administration and intramammary infusion of
      antigen and viable or freeze-dried Cryptosporidium parvum oocyst solution
      emulsified with Freund's complete and incomplete adjuvant. Two animals served as
      controls and another two as adjuvant controls. Serum was collected at first
      immunization and thereafter every 2 to 4 weeks. Colostrum and milk were collected
      as well. All samples were assayed for C. parvum-specific antibodies using an
      enzyme-linked immunosorbent assay methodology, and Western blotting was used to
      recognize the C. parvum antigens. Hyperimmunization resulted in a progressive and
      significant increase in specific anti-C. parvum serum IgG, IgA and IgM titres,
      with the highest values noted at the point of lambing. Titres decreased slightly
      in milk, although they were in all cases higher than those in the control
      animals. Moreover, some 30 bands of C. parvum were recognized.

PMID- 16292683
TI  - The effect of closed wedge high tibial osteotomy on tibial slope: a radiographic
      study.
AB  - In recent years there has been a renewed interest in high tibial osteotomies
      (HTOs). The development of new instruments and better fixation devices has
      significantly simplified the surgical procedure. This technique is frequently
      used to correct alignment in the frontal plane. However, changes in the sagittal
      plane following closed wedge HTO have not been appropriately investigated. Hence,
      the purpose of this study was to investigate any possible alteration of the
      tibial slope introduced by closed wedge HTO. In addition, we also investigated
      whether there is a correlation between changes of the frontal plane and
      alteration of the tibial slope in the sagittal plane. In a retrospective study,
      radiographs of 67 patients (41 males, mean age 36.6 and 26 females, mean age 39.4
      years) who underwent a closed wedge HTOs or removal of hardware for a previous
      HTO were reviewed. The frontal plane was corrected by a mean of 7.9 degrees (6-14
      degrees). The mean posterior tibial slope on the preoperative images averaged 6.1
      degrees (0-12 degrees). The postoperative radiographs demonstrated a significant
      (P=0.0001) decrease of the posterior tibial slope to a mean of 1.2 degrees . The
      magnitude of HTO in the frontal plane had no significant effect (P=0.739) on the
      postsurgical posterior tibial slope in the sagittal plane.

PMID- 16292684
TI  - Evidence-based medicine--from best research evidence to a better surgical
      practice and health care.
AB  - BACKGROUND: The use of the terms evidence-based medicine (EBM) and healthcare
      (EBHC) has become commonplace in the medical as well as in the surgical
      literature. Using the best available evidence, however, is not yet a working
      routine among surgeons because of the large amount and complexity of published
      research and the lack of user-friendly tools and necessary skills for the use of
      research results. DISCUSSION: This article encourages to formulate surgically
      relevant questions and to answer them on the basis of high-quality research,
      preferably by using systematic reviews which are based on the quality criteria of
      the Cochrane Collaboration. CONCLUSIONS: As currently only 77 Cochrane reviews
      address surgical procedures; much work remains to be done to enlarge the number
      of high-quality and relevant reviews. Similarly, the number and quality of
      randomized controlled trials need to be increased in all surgical specialties.

PMID- 16292682
TI  - A prospective comparison of bone-patellar tendon-bone and hamstring grafts for
      anterior cruciate ligament reconstruction in female patients.
AB  - The aim of the study is to compare the results after arthroscopic anterior
      cruciate ligament (ACL) reconstruction using central-third, bone-patellar tendon
      bone (BTB group) (n = 28) and four-strand semitendinosus/gracilis (ST/G group) (n
      = 31) autografts in female patients. The type of study was non-randomised
      prospective consecutive series. A consecutive series of 61 female patients, all
      with unilateral ACL ruptures, was included in the study. In both groups,
      interference screw fixation of the graft was used at both ends, and 59/61 (97%)
      of the patients returned for the follow-up examination after a period of 26 (23
      31) months. The pre-operative assessments in both groups were similar in terms of
      the Lysholm score, KT-1000 measurements, one-leg-hop test, and knee-walking test.
      At the 2-year follow-up, the knee-walking test was significantly worse in the BTB
      group than in the ST/G group (P = 0.003). Furthermore, the knee-walking test was
      significantly worse at follow-up than pre-operatively in the BTB group (P <
      0.005). The corresponding finding was not made in the ST/G group. A reduction in
      knee laxity compared with the pre-operative assessments was found in both groups.
      No significant difference in the post-operative knee laxity measurement was found
      between the groups. A significant increase in activity level and subjective
      scores was found in both groups compared with pre-operative values, without any
      significant differences between the groups. Two years after ACL reconstruction,
      the groups displayed no significant differences in terms of functional outcome
      and knee laxity. However, the use of ST/G autografts rendered significantly less
      discomfort during the knee-walking test than the use of BTB autografts.

PMID- 16292717
TI  - Risk and protective factors for drug abuse in adolescents. A longitudinal
      research.
AB  - INTRODUCTION: The aim of the present study was to identify possible risk and
      protective factors for the development of problems with the use of drugs in
      adolescents. METHODS: A two years follow-up was carried out (from the 2nd to the
      4th year of the Compulsory Secondary Education). Sociodemographic variables,
      general and eating psychopathology, family functioning and patterns of drugs use
      were assessed in 1,076 students. RESULTS: After controlling the effect of having
      problems with the use of drugs at the beginning, cigarettes smoking at the age of
      13 years predicted the consumption of alcohol 2 years later and vice versa.
      Independently of the effect of this association, general psychopathology, body
      image dissatisfaction and self-harm at the beginning were risk factors for
      alcohol consumption 2 years later. Moreover, besides female gender and high
      academic achievements, normal family functioning was a protective factor against
      the fact of suffering problems with drugs later on. CONCLUSIONS: These present
      findings might have relevance in the development of preventive strategies for the
      use of drugs in adolescent population.

PMID- 16292719
TI  - Assessment of expressed emotion in families of patients with eating disorders:
      using the Camberwell Family Interview on a Spanish sample.
AB  - INTRODUCTION: The level of expressed emotion (EE) in the family members has been
      related to several clinical and outcome related factors in patients with eating
      disorders. This study aimed to study the levels of EE in families of patients
      with eating disorders using the Camberwell Family Interview (CFI) in order to
      determine whether they were similar to those reported in other studies developed
      outside Spain. METHODS: Seventy-one parents of 43 eating disorders patients were
      evaluated using a Spanish version of the CFI. RESULTS: In our sample, 46.5 % of
      the families had EE high levels. There were no significant differences between
      mothers and fathers in global scores, but mothers tended to have higher emotional
      overinvolvement with the patient. CONCLUSIONS: The percentage of families that
      had high EE in our sample was lower than that reported for families with a member
      with schizophrenia and slightly higher than that detected in other studies on
      eating disorders. Mothers tended to have higher EE levels than fathers.

PMID- 16292718
TI  - Regional cerebral blood flow SPECT study, at rest and during Wisconsin Card
      Sorting Test (WCST) performance, in schizophrenia naive patients or treated with
      atypical neuroleptics.
AB  - INTRODUCTION: To corroborate the hypothesis of hypofrontality in schizophrenia
      and to study the relationship between positive/negative symptoms (measured by the
      positive and negative syndrome scale [PANSS]) and regional cortical blood flow
      (rCBF), both at rest and during the Wisconsin Card Sorting Test (WCST)
      performance (activation). METHODS: We compared a control group (n = 18) to a
      group of patients with schizophrenia (n = 21) in terms of rCBF, measured by
      single photon emission computed tomography (SPECT). RESULTS: We found
      significantly higher left-frontal- CBF (during the WCST performance and at rest)
      and right-frontal-CBF (only at rest) in control subjects. Only the control group
      showed a right-frontal-CBF increase during activation. Only the patients group
      showed a significant right-occipital-CBF increase during the activation. We
      observed a positive significant correlation between the PANSS-P score and the
      left- frontal index at rest. Some negative symptoms such as difficulty in
      abstract thinking (N5) and lack of spontaneity and flow of conversation (N6) are
      associated to low frontal blood flow at rest. Affective blunting (N1) is
      associated to low left-frontal blood flow during activation. CONCLUSIONS: Our
      data support the hypothesis of hypofrontality, at rest and during activation,
      which means the incapacity of schizophrenic patients to increase the frontal CBF
      while performing the WCST (activation). Schizophrenia positive symptoms are
      associated to high left-frontal blood flow.

PMID- 16292720
TI  - Psychological risk and protective factors for antisocial behavior in adolescents.
AB  - The aim of this paper is to analyze the influence and differential weight of some
      specific psychological variables on adolescent antisocial behavior. A sample of
      1,851 adolescents (49.92 % men and 50.08 % women) from the Autonomous Community
      of Madrid was assessed. Several stepwise regression analyses were conducted,
      considering three different age groups (14-15, 16 and 17-18 years), with the
      criterion variables and the results showed that the main psychological risk
      factors associated with antisocial behavior were variables linked to sensation
      seeking construct (impulsiveness, disinhibition, excitement seeking, etc.), while
      the protective factors identified were variables such as empathy and religious
      practices. The age groups were considered, keeping a design of optimum prevention
      programs with psychological character in mind.

PMID- 16292721
TI  - Analysis of convergent and discriminant validity of the Spanish experimental
      version of the State-Trait Depression Questionnaire (ST-DEP).
AB  - INTRODUCTION: This article reports data on the convergent and divergent validity
      of the Spanish adaptation of Spielberger's State-Trait Depression Questionnaire
      (ST-DEP). This questionnaire is a new tool because it offers an alternative to
      the obstacles found in most of the depression assessment scales that are
      differentiated in the content they evaluate and their estimation of depression
      levels. METHODOLOGY: The present study was carried out with a sample of 300
      participants (103 males and 197 females), with mean age of 21.82 (2.74 s.d.) for
      males and 22.26 (3.66 s.d.) for females. All participants received information
      about the investigation and participated voluntarily. RESULTS AND CONCLUSIONS:
      The results indicate high and significant correlations of the Spanish ST-DEP
      scales with other depression measures (BDI, BDQ-R), thus showing the convergent
      validity of this questionnaire. Highly significant correlations between the
      Spanish ST-DEP and the State-Trait Anxiety Inventory (STAI) also appear,
      confirming that reported about the comorbidity between both disorders and the
      high scores in anxiety that subjects with depression have. In contrast,
      correlations with the State-Trait Anger Expression Inventory (STAXI-2) were low
      and non-significant in most cases, which demonstrated the divergent validity of
      the ST-DEP.

PMID- 16292722
TI  - Emotional auditory paradigm in neuroimaging: a base for the study of psychosis.
AB  - INTRODUCTION: Since the arrival of neuroimaging numerous studies have tried to
      analyze the differences between emotional and non-emotional response. The
      majority of these studies use visual approach (faces) and begin with data in
      normal subjects. The present study introduces a new paradigm for the study of
      emotional response based on auditory approach and designed specifically for the
      study of psychoses. METHOD: The most frequent words heard by psychotic patients
      with auditory hallucinations were analyzed. They were classified according to
      five categories which were compared with 13 other words with the same structure
      but with a neutral emotional valency. This paradigm was applied to see the
      cerebral activation with functional magnetic resonance imaging (fMRI) in 10 right
      handed healthy males. RESULTS: In the preliminary analysis a clear
      differentiation is observed depending on the type of stimulus applied (emotional
      or non-emotional), both in the intensity of activation (right and left temporal
      cortex) as in the activation of specific areas (right precentral and
      supramarginal gyrus) only with the emotional stimulus. CONCLUSIONS: The present
      paradigm allows the observation of a differentiation in the cerebral activation
      to emotional auditory stimulus and could be of utility in the study of psychotic
      patients.

PMID- 16292723
TI  - Concepts, theories and psychosocial factors in cancer adaptation.
AB  - The impact of psychological factors is increasingly taken into consideration in
      cancer patient care. In this review, we focus on the explicative models and the
      factors involved in psychosocial adaptation to cancer. Concerning the former, we
      present the latest reviews on stress and coping paradigm as applied to psycho
      oncology. Specifically, we discuss the psychological mechanisms that make it
      possible to manage emotional distress related with cancer and that determine the
      different degrees of adaptation to the disease. This explanation is illustrated
      with two examples. On the other hand, the role of several variables that
      influence adaptation to cancer, grouped as sociocultural, psychological and
      medical variables, is discussed. Sociocultural variables make it possible to
      identify which patients have an increased risk of developing psychological
      distress symptoms. The psychological variables, include the different coping
      strategies, psychiatric history, psychological distress and concerns and fears.
      The impact of sociocultural and psychological variables is illustrated with two
      case examples. The medical variables are associated with the disease stage,
      treatment and prognosis. Finally, we discuss in what way these models, concepts
      and factors allow for design interventions adapted to the specific needs of each
      patient.

PMID- 16292724
TI  - Ziprasidone overdose: cardiac safety.
AB  - Ziprasidone is a neuroleptic drug recently sold in Spain. According to its
      profile of receptors it is considered an atypical or second generation
      antipsychotic agent. Its use has been associated to increase of the QT interval,
      which might trigger potentially lethal ventricular arrhythmia. We present a case
      of overdose with moderate doses of the drug, in which there were no important
      changes in the QT interval. A review of the cases of overdose published up to now
      was also done.

PMID- 16292725
TI  - Eosinophilic pleural effusion secondary to treatment with valproic acid.

PMID- 16292726
TI  - Significant angiogenic potential is present in the microenvironment of muscle
      flaps in humans.
AB  - The purpose of this study was to determine the presence of growth factors and the
      quality of angiogenic potential in the wound microenvironment in different types
      of flaps in humans. The wound exudates from 23 flaps were processed for analysis
      of transforming growth factor beta1 (TGF-beta1), epidermal growth factor (EGF),
      interleukin 1alpha (IL-1alpha), platelet-derived growth factor-AB (PDGF-AB),
      vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF-1)
      by enzyme-linked immunosorbent assay (ELISA) or radio immuno assay (RIA).
      Angiogenic activity of wound fluid from latissimus flaps was determined by
      thymidine incorporation in porcine microendothelial cells exposed to various
      concentrations of wound fluid and control media. Angiogenic and matrix growth
      factors were altered in a linear fashion during the wound-healing process.
      Regression analysis provided evidence for decreasing levels of PDGF and EGF for
      latissimus flaps. Also, statistically significant differences of growth factor
      levels were found for paired comparison of flap types at different times after
      operation. Growth of in-vitro endothelial cells was stimulated most by 10 percent
      wound fluid, compared to any of the individual recombinant angiogenic factors or
      combinations of these factors. The data suggest that vascularized tissue flaps
      will promote wound healing by providing sufficient sources of growth factors in
      the wound environment. The particular type of flap, i.e., muscle or
      fasciocutaneous flap, does not seem to have an impact on growth-factor
      expression.

PMID- 16292727
TI  - Cavernous nerve reconstruction during radical prostatectomy by sural nerve
      grafting: surgical technique in nerve harvesting and grafting.
AB  - The authors performed cavernous nerve reconstruction by nerve grafting in 22
      patients (unilateral-16, bilateral-6) between August 2001 and June 2004.
      Harvesting of the sural nerve was unexpectedly more difficult than nerve grafting
      in the extremities or the head and neck, because a knee and lumbar bending
      position was impossible due to the pelvic surgical field. Suture of the grafted
      nerve on the distal side required great effort, because there was only sufficient
      space for one hand at the maximum in a deep region of the pelvic cavity, and the
      nerve ends easily become invisible by inflow of even a small amount of urine or
      blood. The mean time of the nerve harvesting and grafting was 1 hr 50 min for
      unilateral grafting and 2 hr 40 min for bilateral grafting. Recovery of erectile
      function was observed in about half the patients who had undergone surgery nearly
      1 year before. Since harvesting of the sural nerve and nerve grafting were more
      difficult than expected, modification and improvement of many surgical elements,
      such as improvement of surgical devices and application of endoscopic techniques,
      are necessary.

PMID- 16292729
TI  - Devascularizing complications of free fibula harvest: peronea arteria magna.
AB  - The authors present a case report of devascularizing complications following free
      fibula harvest. A retrospective review of 93 consecutively imaged limbs
      demonstrated a peronea arteria magna (PAM) prevalence of 5.3 percent in an urban
      population, which was used to perform a cost-effectiveness analysis for
      preoperative vascular imaging of the donor limb using magnetic resonance
      angiography (MRA) and traditional angiography (TA). Donor-site complications of
      fibula harvest range from 15 to 30 percent, but are rarely limb-threatening. Limb
      loss is a dreaded complication of congenital PAM, which can be present with a
      normal vascular exam. Some microsurgery groups advocate using no preoperative
      imaging of the donor limb; they rely on intraoperative assessment of the vascular
      anatomy. An aborted harvest due to aberrant anatomy leads to both direct and
      indirect added costs. The authors believe that MRA imaging of the donor limb,
      being minimally invasive, is cost-effective and indicated for free fibula
      transfers. For equivocal results, conversion to more invasive and costly TA may
      be necessary.

PMID- 16292731
TI  - Direct microvascular repair of an infant's transected coronary artery: case
      report.
AB  - The authors report the direct, microvascular repair of a right coronary artery
      transected during reoperation fOr complications of arterial switch operation
      (ASO) in a 3 month-old child. This is the first documented use of direct
      microsurgical anastamosis in the repair of an infant's transected coronary
      artery. Deviation from standard coronary bypass graft repair was permitted by
      vessel characteristics, as well as close collaboration between plastic surgery
      and cardiac surgery services. Patency of repair was confirmed intraoperatively
      with Doppler ultrasound and through postoperative echocardiograms documenting
      stable right ventricular function. This case highlights the benefit of a
      multidisciplinary approach to an emergent clinical problem using microsurgical
      techniques.

PMID- 16292730
TI  - Rationale for reconstruction of large scalp defects using the anterolateral thigh
      flap: structural and aesthetic outcomes.
AB  - The advent of free tissue transfer has provided multiple options that allow
      preservation and maintain both the structural and aesthetic status of the scalp.
      Since the first report of the anterolateral thigh flap in 1984, it has become one
      of the most commonly used flaps for the reconstruction of various soft-tissue
      defects. Eleven free anterolateral thigh flaps were used to reconstruct soft
      tissue defects of different regions of the scalp. Two of these flaps were used
      for the occipital region, six for temporal regions, two for the frontoparietal
      midline region, and the remaining flap for a defect of the forehead. The study
      consisted of 10 males and one female whose ages ranged from 18 to 82 years (mean
      age: 52.5 years). Six patients had primary or recurrent cancer, four had acute or
      subacute wounds resulting from trauma or craniotomy, and one had high-tension
      electrical burn injury. The size of the flaps ranged from 14 to 27 cm in length
      and from 6 to 18 cm in width. The overall flap success rate was 100%. In two
      cases, primary thinning of the flap was performed to reconstruct a tissue defect
      of the temporal region in one patient and a forehead defect in the other. In two
      patients, the fascial layer of the flap was used as a source for a vascularized
      fascial flap to cover defects of the dura mater. No secondary corrections,
      including debulking procedures or scar revision, were necessary. No infections or
      hematomas were observed. Six cases underwent split-thickness skin grafting of the
      donor site and, in the remaining cases, the donor sites were closed directly. No
      donor-site morbidity was observed. The authors conclude that with its evident
      structural and cosmetic advantages, the anterolateral thigh flap can be
      considered an excellent flap option for most scalp defects.

PMID- 16292733
TI  - Role of blood transfusion in transplantation: a review.
AB  - The ultimate goal of transplantation immunology is induction of donor-specific
      tolerance without the need for chronic immunosuppression. A number of strategies
      have been used to induce tolerance, including donor-specific blood transfusion
      (DST). A large number of experimental and clinical studies have evaluated the
      ability of DST to induce tolerance in solid organ transplantation. In contrast, a
      limited number of experimental studies have been reported evaluating the effect
      of DST in induction of tolerance in composite tissue allograft transplants. DST
      applications include cadaveric and living-related graft recipients in humans,
      leading to achievement of microchimerism. Although the mechanism of action is
      still uncertain, microchimerism with the concomitant persistence of soluble donor
      HLA antigen is considered to be the most significant contributing factor. In this
      article, the experimental and clinical applications, as well as the
      immunomodulatory mechanism of DST, are reviewed.

PMID- 16292732
TI  - Posterior tibial adiposal flap for repair of wide, full-thickness defect of the
      Achilles tendon.
AB  - Wide, full-thickness defects on the posterior aspect of the distal lower leg
      involving the Achilles tendon are usually repaired with free fasciocutaneous
      flaps or local skin flaps. The former require microvascular techniques; there is
      a donor-site scar due to skin grafting; and a longer operating time. The latter
      results in a wide scar near the donor defect. The authors developed a new
      reconstructive procedure using local fascia turned over to create a new Achilles
      tendon, and wrapping it with a posterior tibial adiposal island flap based on the
      dominant perforator of the posterior tibial artery, which was elevated from the
      medial aspect of the lower leg. The advantages of this method are that no donor
      scar appeared on the posterior aspect of the lower leg, and there was no need for
      microvascular techniques. This method is especially suitable for young women.

PMID- 16292734
TI  - Bridging small-gap peripheral nerve defects using biodegradable chitin conduits
      with cultured schwann and bone marrow stromal cells in rats.
AB  - Nerve regeneration requires not only an autologous, allogenous, or biodegradable
      scaffolding, but additional interactions with regeneration-promoting Schwann
      cells. Considering the pluripotency of bone marrow stromal cells into different
      lineages, the authors compared biodegradable conduits with the application of
      cultured Schwann cells and bone marrow stromal cells in a rat sciatic injury
      model. Simple conduit bridging served as controls. Electrophysiologic evaluation
      and histologic morphometrical analysis were performed after 6 weeks; both groups
      with cultured cells showed a statistically significantly higher number of axons,
      more well-shaped remyelinated axons, and an advance in clinical functional
      recovery (SFI) than the simple conduit-bridging group. Confocal microscopy found
      that bone marrow stromal cells adopted the Schwann-cell phenotype, expressing
      S100 protein. Considering the ease of aspiration and greater resource of bone
      marrow stromal cells, the implantation of a biodegradable conduit with cultured
      bone marrow stromal cells was capable of presenting an alternative to conduits
      with Schwann cells for bridging nerve defects.

PMID- 16292736
TI  - End-to-side nerve grafts: experimental study in rats.
AB  - The effectiveness of the end-to-side nerve graft in comparison with the end-to
      end cable-graft was determined in rat sciatic nerve transection models. Sixty
      Sprague-Dawley rats were randomly divided into four groups with different
      reconstructive methods for two branches of the sciatic nerve: Group I, median
      nerve graft with end-to-side neurorrhaphy; Group II, median and ulnar nerve
      grafts with end-to-end neurorrhaphy; Group III, no repair; and Group IV, sham
      operation. Between Groups I and II, there were no significant differences in the
      functional, electrophysiologic, and histologic evaluations. In retrograde tracing
      of the spinal cord and dorsal root ganglia, the number of double-labeled neurons
      was significantly higher in Group I. End-to-side nerve grafts show good
      functional recovery, require less graft, and are easy to perform. The authors
      find this method to be an effective alternative in facial nerve reconstruction
      and of great value in various kinds of peripheral nerve surgery.

PMID- 16292735
TI  - Effect of systemic creatine monohydrate supplementation on denervated muscle
      during reinnervation: experimental study in the rat.
AB  - The purpose of this experimental study was to evaluate possible upgrading effects
      of systemic creatine monohydrate administration on the reinnervation of
      denervated muscle. At the same time, the protective effect of the agent on
      denervated muscle until ultimate reinnervation after nerve repair was quantified.
      The functional outcome of muscle reinnervation after creatine monohydrate
      application was compared with a control group. Forty adult Wistar rats weighing
      180 to 220 g were used. The right sciatic nerve was dissected, exposed, and cut
      at the level of the midthigh in all rats. The experimental design consisted of
      two groups: experimental (animals were fed creatine monohydrate) and control
      (gavage feeding was provided by saline). Both groups were divided into two
      subgroups: subgroups A and B for the experimental group, and subgroups C and D
      for the control group. In subgroups A and C, the nerves were repaired with four
      10-0 epineurial stitches. In subgroups B and D, both the proximal and distal ends
      of the nerves were ligated and no neural anastomosis was performed. In the
      experimental groups (subgroups A and B), the rats were fed by daily
      supplementation of oral creatine monohydrate, 300 mg/kg body weight. In the
      controls (subgroups C and D), oral supplementation was provided by saline.
      Functional recovery was evaluated using walking track analysis, pinching test,
      and limb circumference and toe contracture measurements at the end of 6 months,
      after which the rats were sacrificed and nerve specimens from both ends of the
      repair sites and the whole gastrocnemius muscle were obtained to document the
      results of the histomorphometric and histochemical studies, including light
      microscopic examinations and muscle weight measurements. The mean functional
      recovery values in subgroups A, B, C, and D were 91 percent, 80 percent, 87
      percent, and 59 percent, respectively. Functional recovery improved significantly
      in the experimental groups (in both the surgically repaired and unrepaired
      subgroups), compared with the control groups (p<0.05). The pinching test revealed
      a statistically significant difference in nerve conduction between the
      experimental and control groups (p<0.05). The limb circumference ratio of the
      surgically treated side to the untouched side in subgroups A, B, C, and D were
      noted as 0.95, 0.89, 0.91, and 0.87, respectively, and the difference between the
      experimental and the control groups was statistically significant (p<0.05). The
      differences between subgroups A and B, C and D, A and C, and B and D were also
      significant. The surgically repaired and creatine-supplemented subgroups
      demonstrated the best results in toe contracture index. The muscle weight
      measurement results were concordant with the results of the limb circumference
      ratio. In both surgically repaired subgroups (subgroups A and C), there were
      qualitatively significant amounts of myelinated fibers in the nerve distal to the
      anastomotic site; there were no myelinated fibers in the distal stumps of
      subgroups B and D. Histochemical analyses of the contents of the muscle fiber
      types also revealed no significant difference. Overall, the results showed the
      useful effect of oral creatine supplementation on both surgically repaired and
      unrepaired nerve injuries. The best results were obtained from surgically
      repaired nerve injuries and also from the systemic creatine-supplemented
      subgroups. This study confirms that systemic administration of creatine
      monohydrate has a protective and upgrading effect on the functional properties of
      denervated muscle, especially in surgically reinnervated subjects.

PMID- 16292740
TI  - Echo train shifted multi-echo FLASH for functional MRI of the human brain at
      ultra-high spatial resolution.
AB  - This paper describes the development of a novel technique for functional MRI of
      the human brain at 0.135 microL resolution for a whole brain section. In
      comparison with conventional studies at 3 mm isotropic resolution or 27 microL
      voxel size, the method yields an improvement by a factor of 200. To achieve
      optimum image quality, the approach is based on a multi-echo fast low-angle shot
      (FLASH) sequence with unipolar traversals of k-space in the frequency-encoding
      dimension and echo train shifting to avoid amplitude discontinuities in the phase
      encoding dimension. These strategies ensure a smooth point-spread function and
      eliminate image ghosting artifacts without the need for any phase correction or
      other post-processing. Signal-to-noise losses due to the considerably reduced
      voxel sizes are compensated for by single slice acquisitions, optimized
      bandwidths and an experimental four-channel shoulder coil matched to the
      posterior portion of the head. Multi-echo FLASH studies of the human brain (2.9
      T, seven echoes, 200 Hz/pixel bandwidth, effective echo time 36 ms, acquisition
      time 6 s) at 300 microm resolution (no interpolation) and 1.5 mm slice thickness
      revealed robust activations in primary visual areas in response to binocular
      stimulation. The new method holds promise for refined studies of the columnar
      organization of specific brain systems and for functional assessments of the gray
      matter at laminar resolution.

PMID- 16292741
TI  - Quantitative study of changes in oxidative metabolism during visual stimulation
      using absolute relaxation rates.
AB  - In the context of quantitative functional MRI (fMRI), deoxyhemoglobin (dHb)
      content is the essential physiological parameter for calibrating the blood
      oxygenation level-dependent (BOLD) signal. In studies on humans, the baseline dHb
      content or its equivalent has been evaluated indirectly by means of carbon
      dioxide breathing as a physiological reference condition. In this study with
      normal volunteers, quantitative mapping of baseline dHb content was performed in
      a direct manner by measuring the reversible contribution of the effective
      transverse relaxation rate. The BOLD signal change in the visual cortex during 8
      Hz flicker visual stimulation was calibrated based on the quantitative map of
      baseline dHb content. The calibrated relaxation rate change that represents the
      stimulation-induced fractional change of dHb content decreased by 14% within the
      activated visual cortex. Simultaneous measurement of cerebral blood flow (CBF)
      with BOLD showed an increase of 59%. From the calibrated relaxation rate and CBF
      changes, the cerebral metabolic rate of oxygen (CMRO2) was calculated to increase
      by 19-28% within the activated visual cortex. The ratio of the CBF increase to
      the CMRO2 increase was 2-3:1, which agreed well with results of similar
      quantitative fMRI studies for humans. The method proposed here for quantitative
      evaluation of the BOLD signal may be applicable not only to fMRI for normal human
      subjects, but also to physiologically altered or diseased states, because it
      requires no physiological perturbation.

PMID- 16292742
TI  - Role of phosphorylated Thr160 for the activation of the CDK2/Cyclin A complex.
AB  - The enzymatic activity of the CDK2/Cyclin A complex increases upon the specific
      phosphorylation of Thr160@CDK2. In the present study, we have performed a
      comparative molecular dynamics (MD) study of models of the complex CDK2/Cyclin
      A/Substrate, which differ for the presence or absence of the phosphate group
      bound to Thr160. The models are based on two X-ray structures available for
      CDK2/CyclinA and pCDK2/CyclinA/Substrate complexes. In this way, we analyze the
      influence of the phosphorylated Thr160 (pThr160) on both the flexibility of CDK2
      activation loop (AL) and substrate binding in CDK2. Our calculations point to a
      decreased flexibility of the AL in the phosphorylated model, in fairly good
      agreement with experimental data, and to a key role of pThr160 for substrate
      recognition and stability. Multiple alignments of the CDKs sequences point to the
      very high conservation of the AL sequence among the CDKs, thus extending our
      results to all CDKs.

PMID- 16292743
TI  - Grossly-resected synovial sarcoma treated by the German and Italian Pediatric
      Soft Tissue Sarcoma Cooperative Groups: discussion on the role of adjuvant
      therapies.
AB  - Differently from adult oncologists that considered synovial sarcoma (SS) a tumor
      with uncertain chemosensitiveness, since two decades pediatric oncologists in
      Europe assumed that chemotherapy played an important role in SS treatment, so
      most pediatric patients were included in rhabdomyosarcoma protocols, receiving
      adjuvant chemotherapy regardless of risk factors. The German and Italian groups
      reviewed the data of grossly resected SS patients in order to define a risk
      adapted treatment program for the next European protocol. A total of 150 patients
      < 21 years with localized SS who underwent initial gross resection between 1975
      and 2002 were the object of this study. All but four cases received adjuvant
      chemotherapy. Post-operative radiotherapy was administered to 50% Group I and to
      92% Group II patients. Five-year event-free survival (EFS) and overall survival
      (OS) were 77% and 89%, respectively. Survival rates were influenced by tumor size
      (EFS 92% and 56% for size < or = and > 5 cm, respectively) and local
      invasiveness, not by surgical margins. No metastatic relapses occurred in Group I
      < or = 5 cm patients, while the outcome was poor for T2B patients (EFS 41%) due
      to a high rate of metastatic relapse. Our study was unable to assess the role of
      adjuvant treatments in grossly-resected SS, but identified a subset of low-risk
      patients (IRS Group I, size < or = 5 cm), for which the omission of adjuvant
      chemotherapy could be suggested, and a subset of high-risk patients (T2B), who
      need treatment intensification.

PMID- 16292744
TI  - Characterization of a microparticulate strong anion-exchanger in the HPLC of
      acidic drugs.
AB  - The use of Waters Spherisorb S5SAX for the HPLC of acidic compounds, including a
      number of non-steroidal anti-inflammatory drugs (NSAIDs), has been investigated.
      Adequate retention, separation, and peak efficiency and symmetry were obtained
      for most analytes on a 250 x 4.6 mm i.d. column using methanol containing
      ammonium perchlorate (10 mmol L(-1), pH 6.7 or pH 8.3) as eluent. The results of
      changes in (i) eluent pH (constant ionic strength); (ii) eluent ionic strength
      (constant pH); and (iii) adding water to the eluent (constant pH) were consistent
      with a retention mechanism dominated by ion-exchange with the bonded strong anion
      exchange (SAX) moieties. However, there were some unexpected observations,
      including (i) a general decrease in retention at eluent pH values above 7.7; (ii)
      a marked increase in retention on adding 1% (v/v) water to the eluent; (iii) a
      subsequent marked decrease in retention on adding 5% (v/v) or more water; and
      (iv) decreased column activity with time. These observations may be due to (i)
      interaction between the charged SAX moieties and ionised surface silanols (with
      ionization increasing at higher eluent pH values) and (ii) influence of the
      solvation of silanols, analytes, SAX moiety, and counter-ion varying with both pH
      and water content. Nevertheless, the factors influencing separation of individual
      NSAIDs remain unclear especially as no relation between log k and pKa exists for
      these compounds. Hydrophobic interactions are unlikely to be important since
      basic and neutral compounds were hardly retained. Ease of accessibility of the
      counter-ion to the SAX moiety for analyte displacement may be a factor.

PMID- 16292745
TI  - Folding pathway dependence on energetic frustration and interaction heterogeneity
      for a three-dimensional hydrophobic protein model.
AB  - Monte Carlo simulations of a hydrophobic protein model of 40 monomers in the
      cubic lattice are used to explore the effect of energetic frustration and
      interaction heterogeneity on its folding pathway. The folding pathway is
      described by the dependence of relevant conformational averages on an appropriate
      reaction coordinate, pfold, defined as the probability for a given conformation
      to reach the native structure before unfolding. We compare the energetically
      frustrated and heterogeneous hydrophobic potential, according to which individual
      monomers have a higher or lower tendency to form contacts unspecifically
      depending on their hydrophobicities, to an unfrustrated homogeneous Go-type
      potential with uniformly attractive native interactions and neutral non-native
      interactions (called Go1 in this study), and to an unfrustrated heterogeneous
      potential with neutral non-native interactions and native interactions having the
      same energy as the hydrophobic potential (called Go2 in this study). Folding
      kinetics are slowed down dramatically when energetic frustration increases, as
      expected and previously observed in a two-dimensional model. Contrary to our
      previous results in two dimensions, however, it appears that the folding pathway
      and transition state ensemble can be significantly dependent on the energy
      function used to stabilize the native structure. The sequence of events along the
      reaction coordinate, or the order along this coordinate in which different
      regions of the native conformation become structured, turns out to be similar for
      the hydrophobic and Go2 potentials, but with analogous events tending to occur at
      lower pfold values in the first case. In particular, the transition state
      obtained from the ensemble around pfold = 0.5 is more structured for the
      hydrophobic potential. For Go1, not only the transition state ensemble but the
      order of events itself is modified, suggesting that interaction heterogeneity, in
      addition to energetic frustration, can have significant effects on the folding
      mechanism, most likely by modifying the probability of different contacts in the
      unfolded state, the starting point for the folding reaction. Although based on a
      simple model, these results provide interesting insight into how sequence
      dependent switching between folding pathways might occur in real proteins.

PMID- 16292746
TI  - High-performance liquid chromatographic method for simple and rapid determination
      of linezolid in human plasma.
AB  - A simple high-performance liquid chromatographic (HPLC) method was developed and
      validated for rapid quantification of linezolid in human plasma. Protein
      precipitation using a mixture of 5% trichloroacetic acid and methanol (3:1, v/v)
      provided a straightforward method of sample preparation and the internal standard
      eperezolid was employed. A concentration range from 0.20 to 40.0 mg/L was
      utilized to construct calibration curves, and analysis of low- (0.40 mg/L),
      medium- (7.50 mg/L) and high-quality (25.0 mg/L) control samples revealed
      excellent reproducibility (<or=3.88%) and accuracy (<or=4.20%). The recovery of
      both linezolid and eperezolid was approximately 100%. No interference was
      observed at the retention times of linezolid and eperezolid from blank plasma or
      eight commonly used antibiotics. Tests confirmed the stability of linezolid in
      plasma during three freeze-thaw cycles, on the bench during 24 h and during long
      term storage of frozen plasma for up to 12 weeks; in extracts it was stable in
      the HPLC autosampler over 12 h. Overall, this assay offers a highly simplistic
      approach to quantifying linezolid in plasma, and would be well suited to clinical
      pharmacokinetic, pharmacodynamic and toxicodynamic analyses.

PMID- 16292747
TI  - Quantitation of zopiclone and desmethylzopiclone in human plasma by high
      performance liquid chromatography using fluorescence detection.
AB  - A simple, reliable HPLC method using fluorescence detection (excitation 307 and
      emission 483 nm) was developed and validated for simultaneous quantitation of
      zopiclone and its metabolite desmethylzopiclone in human plasma. Following a
      single-step liquid-liquid extraction, the analytes and internal standard
      (zaleplon) were separated using an isocratic mobile phase on a reversed-phase C18
      column. The lower limit of quantitation was 3 ng/mL for zopiclone and 6 ng/mL for
      desmethylzopiclone with a relative standard deviation of less than 5%. A linear
      dynamic range of 3-300 ng/mL for zopiclone and of 6-500 ng/mL for
      desmethylzopiclone was established. This HPLC method was validated with between
      batch precision of 1.7-4.2% and 3.2-7.5% for zopiclone and desmethylzopiclone
      respectively. The between-batch accuracy was 99.4-111.5% and 101.6-104.8% for
      zopiclone and desmethylzopiclone, respectively. Frequently coadministered drugs
      did not interfere with the described methodology. Stability of zopiclone and
      desmethylzopiclone in plasma was excellent, with no evidence of degradation
      during sample processing (autosampler) and 30 days' storage in a freezer. This
      validated method is simple and repeatable enough to be used in pharmacokinetic
      studies.

PMID- 16292750
TI  - Evaluation of cytogenetic effects of lambda-cyhalothrin on human lymphocytes.
AB  - The genotoxic and cytotoxic potential of lambda-cyhalothrin (LCT), a synthetic
      pyrethroid insecticide, was investigated on human lymphocytes cultured in vitro.
      Utilizing the trypan blue dye exclusion technique assay, the LC50 of LCT was
      found to be 28 microM. Based on the LC50 value, it is seen that LCT was highly
      toxic to lymphocyte cultures, among other pyrethroid group of pesticides.
      Chromosomal aberrations induced by LCT were determined using metaphase plate
      spreads of lymphocytes. The chromosomal analysis was recorded using Medi-Image
      software technology. The analysis revealed that more satellite associations and
      gaps were found, which were statistically significant (p < 0.05) when compared to
      controls. Comet assay was used to assess the possibility of LCT to induce the
      damage in DNA, where the increase in comet tail length relates to the extent of
      DNA single strand breaks. The results presented here indicate that in vitro
      assays could be used as indicators of cytotoxicity and genotoxicity of the
      pesticide.

PMID- 16292751
TI  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on vitamin A metabolism in mice.
AB  - This study aimed to clarify the effects of single and repeated administration of
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the activities or expression of
      some metabolic enzymes of retinoids and the influence of supplemental vitamin A
      on changed vitamin A homeostasis by TCDD. In Experiment I, the mice were given a
      single oral dose of 40 mug TCDD/kg body weight, with or without continuous
      administration of 2,500 IU vitamin A/kg body weight/day, and were killed on day
      1, 3, 7, 14, and 28. In Experiment II, the mice were daily given 0.1 microg
      TCDD/kg body weight, with or without supplemental 2,000 IU vitamin A/kg body
      weight, and were killed on day 14, 28, and 42. In both experiments, TCDD
      significantly decreased the hepatic all-trans-retinol level and increased the
      hepatic all-trans-retinoic acid (RA) content, increased the mRNA and enzymatic
      activities of retinal oxidase. In TCDD + vitamin A mice, the all-trans retinol
      content was significantly higher, and the retinal oxidase mRNA was significantly
      lower on day 3 or 7 in Experiment I and on day 14 in Experiment II, compared to
      TCDD-treated mice. The induction of the retinal oxidase may contribute to the
      decrease in hepatic all-trans-retinol level and the increase in hepatic all-trans
      RA caused by TCDD. Supplemental vitamin A might decelerate the effect of TCDD on
      retinal oxidase mRNA.

PMID- 16292753
TI  - Dietary vitamin E reduces labile iron in rat tissues.
AB  - Previous studies have shown that dietary vitamin E reduced generation and/or
      levels of superoxide. As superoxide has potential to release iron from its
      transport and storage proteins, and labile or available form of iron is capable
      of catalyzing the formation of reactive hydroxyl radicals, the effect of dietary
      vitamin E on labile iron pool was studied in rats. One-month-old Sprague-Dawley
      male and female rats were fed a basal vitamin E-deficient diet supplemented with
      0, 20, 200, or 2,000 IU vitamin E/kg diet for 90 days. The levels of labile iron
      were measured in the liver, kidney, spleen, heart and skeletal muscle.
      Additionally, the levels of lipid peroxidation products were measured. The
      results showed that, except for labile iron in the heart of male rats, dietary
      vitamin E dose dependently reduced the levels of labile iron and lipid
      peroxidation products in all tissues of male and female rats. The findings
      suggest that dietary vitamin E may protect against oxidative tissue damage by
      reducing the generation and/or level of superoxide, which in turn attenuates the
      release of iron from its protein complexes.

PMID- 16292752
TI  - Inhibition of cholinephosphotransferase activity in lung injury induced by 2
      chloroethyl ethyl sulfide, a mustard analog.
AB  - Exposure to mustard gas causes inflammatory lung diseases including acute
      respiratory distress syndrome (ARDS). A defect in the lung surfactant system has
      been implicated as a cause of ARDS. A major component of lung surfactant is
      dipalmitoyl phosphatidylcholine (DPPC) and the major pathway for its synthesis is
      the cytidine diphosphocholine (CDP-choline) pathway. It is not known whether the
      ARDS induced by mustard gas is mediated by its direct effects on some of the
      enzymes in the CDP-choline pathway. In the present study we investigated whether
      mustard gas exposure modulates the activity of cholinephosphotransferase (CPT)
      the terminal enzyme by CDP-choline pathway. Adult guinea pigs were
      intratracheally infused with single doses of 2-chloroethyl ethyl sulfide (CEES)
      (0.5 mg/kg b.wt. in ethanol). Control animals were injected with vehicles only.
      The animals were sacrificed at different time and the lungs were removed after
      perfusion with physiological saline. CPT activity increased steadily up to 4 h
      and then decreased at 6 h and stabilized at 7 days in both mitochondria and
      microsomes. To determine the dose-dependent effect of CEES on CPT activity we
      varied the doses of CEES (0.5-6.0 mg/kg b.wt.) and sacrificed the animals at 1 h
      and 4 h. CPT activity showed a dose-dependent increase of up to 2.0 mg/kg b.wt.
      of CEES in both mitochondria and microsomes then decreased at 4.0 mg/kg b.wt. For
      further studies we used a fixed single dose of CEES (2.0 mg/kg b.wt.) and fixed
      exposure time (7 days). Lung injury was determined by measuring the leakage of
      iodinated-bovine serum albumin into lung tissue and expressed as the permeability
      index. CEES exposure (2.0 mg/kg b.wt. for 7 days) caused a significant decrease
      of both CPT gene expression (approximately 1.7-fold) and activity (approximately
      1.5-fold) in the lung. This decrease in CPT activity was not associated with any
      mutation of the CPT gene. Previously we reported that CEES infusion increased the
      production of ceramides which are known to modulate PC synthesis. To determine
      whether ceramides affect microsomal CPT activity the lung microsomal fraction was
      incubated with different concentrations of C(2)-ceramide prior to CPT assay. CPT
      activity decreased significantly with increasing dose and time. The present study
      indicates that CEES causes lung injury and significantly decreases CPT gene
      expression and activity. This decrease in CPT activity was not associated with
      any mutation of the CPT gene is probably mediated by accumulation of ceramides.
      CEES induced ceramide accumulation may thus play an important role in the
      development of ARDS by modulating CPT enzyme.

PMID- 16292754
TI  - Activation of caspase-3-dependent and -independent pathways during 7
      ketocholesterol- and 7beta-hydroxycholesterol-induced cell death: a morphological
      and biochemical study.
AB  - On treatment with 7-ketocholesterol (7-keto) or 7beta-hydroxycholesterol (7beta
      OH), which are major oxysterols in atherosclerotic plaques, the simultaneous
      identification of oncotic and apoptotic cells suggests that these compounds
      activate different metabolic pathways leading to various modes of cell death.
      With U937, MCF-7 (caspase-3 deficient), MCF-7/c3 cells (stably transfected with
      caspase-3), we demonstrate that caspase-3 is essential for caspase-9, -7, -8
      activation, for Bid degradation mediating mitochondrial cytochrome c release, for
      cleavage of poly(ADP-ribose) polymerase and inhibitor of the caspase-activated
      deoxyribonuclease, and, at least in part, for internucleosomal DNA fragmentation.
      The crucial role of caspase-3 was supported by the use of z-VAD-fmk and z-DEVD
      fmk, which abolished apoptosis and the associated events. However, inactivation
      or lack of caspase-3 did not inhibit 7-keto- and 7beta-OH-induced cell death
      characterized by staining with propidium iodide, loss of mitochondrial potential.
      The mitochondrial release of apoptosis-inducing factor and endonuclease G was
      independent of the caspase-3 status, which conversely played major roles in the
      morphological aspects of dead cells. We conclude that caspase-3 is essential to
      trigger 7-keto- and 7beta-OH-induced apoptosis, that these oxysterols
      simultaneously activate caspase-3-dependent and/or -independent modes of cell
      death.

PMID- 16292755
TI  - Vitamin E supplementation alters HDL-cholesterol concentration and paraoxonase
      activity in rabbits fed high-cholesterol diet: comparison with probucol.
AB  - Vitamin E and probucol are well-known antioxidants that prevent cells from the
      oxidative stress, which is a risk factor of atherosclerosis. Male rabbits were
      fed either 0.03% vitamin E or 0.05% probucol in a 0.5% high-cholesterol (HC) diet
      for 8 weeks. Vitamin E and probucol significantly suppressed an increase in
      plasma total-cholesterol (total-C) and low-density lipoprotein cholesterol
      compared to HC-control group. However, plasma high-density lipoprotein
      cholesterol (HDL-C) and HDL-C/total-C ratio levels and plasma paraoxonase
      activity were only significantly higher in vitamin E group after 8 weeks. Hepatic
      ACAT activity was significantly lower in both vitamin E and probucol groups than
      in HC-control group, while HMG-CoA reductase activity was the highest only in the
      probucol group. Total fecal sterol content was significantly higher in probucol
      and vitamin E groups than in the two control groups. Some atherogenic signs were
      discovered in the aortic fatty streak of HC-control group, yet not in other
      groups. Hepatic mRNA expressions of apo B-100 and apo C-III were significantly
      lower in probucol group than in other groups. Vitamin E supplementation was found
      to alter the plasma HDL-C-related factors; meanwhile, probucol supplementation
      was very effective in enhancing cholesterol metabolism, except for a negative
      effect that reduced plasma HDL-C concentration.

PMID- 16292756
TI  - Liver prenylated methylated protein methyl esterase is an organophosphate
      sensitive enzyme.
AB  - Prenylation and subsequent methylation are essential modifications on a
      significant proportion of eucaryotic proteins. Proteins such as the G-gamma
      subunits of G-protein coupled receptors, nuclear lamins, and guanine nucleotide
      binding proteins such as Ras are prenylated and undergo methylation. Prenylated
      methylated protein methyl esterase (PMPMEase) readily hydrolyses the prenylated
      protein methyl esters, thus making this step reversible and possibly regulatory.
      Benzoyl-glycyl-farnesyl-cysteine methyl ester (BzGFCM) was developed as a
      specific PMPMEase substrate and characterized by electron spray ionization mass
      spectrometry (ESI-MS) to be of the calculated molecular mass. Rat liver and brain
      PMPMEase hydrolyzed BzGFCM, forming benzoyl-glycyl-farnesyl-cysteine (BzGFC) in a
      time- and concentration-dependent manner. Both enzymes cleaved BzGFCM with K(m)
      values of 4.58 +/- 0.30 and 25.57 +/- 2.36 microM and V(max) values of 2.21 +/-
      0.03 and 0.17 +/- 0.003 nmol/min/mg, respectively. The liver enzyme eluted from a
      gel-filtration column as a single peak of apparent size, 89 kDa. The brain enzyme
      eluted as two main peaks of 53 and 890 kDa. Organophosphorus pesticides (OPs),
      which are suspected to be involved in human disorders such as parkinsonism,
      neuronal, and retinal degeneration, inhibited the liver enzyme with IC(50) values
      from 4.77 muM for parathion to 0.04 microM for paraoxon, respectively. Only about
      25% of the brain enzyme was inhibited by 0.5-1 mM solutions of mipafox, while 0.1
      and 1 mM paraoxon inhibited over 50% and 95% of the enzyme, respectively.
      Paraoxon is thus about 2,250 times less potent against the brain than the liver
      PMPMEase. BzGFCM was not hydrolyzed by various cholinesterases, indicating its
      specificity for PMPMEase. Perturbations in prenylated protein metabolism might
      play a role in noncholinergic OPs-induced toxicity, since prenylated proteins
      play such important roles in cell signaling, proliferation, differentiation, and
      apoptosis.

PMID- 16292757
TI  - Effects of xenobiotics and peroxisome proliferator-activated receptor-alpha on
      the human UDPglucose dehydrogenase gene expression.
AB  - During drug metabolism, UDPglucuronate, a product of the reaction catalyzed by
      the enzyme UDPglucose dehydrogenase (UGDH), is conjugated with the metabolites to
      facilitate their elimination. So far, it is not known whether xenobiotics can
      modulate the UGDH gene expression. This question was tested by treating the human
      hepatoma cells HepG2 with several medicinal compounds and the UGDH gene
      expression analyzed by using real-time PCR. Both eugenol and rifampicin showed
      activation of the gene expression. Piperine showed slight down-regulation of the
      UGDH gene expression, whereas no effect was observed with acetaminophen
      treatment. Through promoter-reporter gene assays, we found that rifampicin showed
      multiple-folds activation of a 1.23-kb UGDH promoter construct, the region likely
      to respond to rifampicin treatment is located within the range -632 to -1,050. A
      bioinformatics search for xenobiotic response element in this region has
      predicted a binding motif for the peroxisome proliferator-activated receptor
      alpha(PPARalpha) at position -1,003. A mutation at the predicted PPAR recognizing
      motif eliminated normal suppression as well as the rifampicin activation effect
      on the UGDH promoter activity. Cotransfection with the PPARalpha and retinoid X
      receptor-alpha expression vectors and subsequent treatment with the PPARalpha
      agonist led to the suppression of the UGDH promoter activity either in the
      presence or absence of rifampicin. Our study, for the first time, shows the UGDH
      gene to be under xenobiotic regulation and delineates a motif responsible for
      rifampicin response and transcriptional repression of the UGDH gene.

PMID- 16292758
TI  - Sculpturing a fibular flap: combined horizontal/vertical osteotomy and ostectomy
      for reconstruction of complex craniofacial defects with one flap.
AB  - A fibular flap has great versatility in reconstructive procedures. Osteomies and
      ostectomies enable the flap to be used for variable defects. We used combined
      horizontal/vertical osteotomy and ostectomy for reconstruction of complex
      craniofacial defects with one flap in two patients. Vertical osteotomy transforms
      the tubular structure of a fibula into a flat bone that can be used for
      reconstruction of wider defects with less vertical height. Neither vertical
      osteotomy nor ostectomy had negative effects on viability and bony healing of the
      segments in our patients. We think that the fibular flap, thanks to its
      versatility, can be used for reconstruction of complex orbito-zygomatic and
      orbito-cranial defects successfully.

PMID- 16292759
TI  - Fabrication of polycaprolactone scaffolds using a sacrificial compression-molding
      process.
AB  - A method of compression-molding fine-powder blends of polycaprolactone (PCL) and
      poly(ethylene oxide) (PEO) and subsequently dissolving the PEO phase was
      investigated to prepare porous PCL scaffolds. Different mixing ratios of the two
      polymers from 20 to 70% PCL were used to study the effect of the mixing ratio on
      the morphology formation of the scaffold. The mixing ratio was found to play an
      important role in affecting the porosity of the scaffold and the size of pores.
      Murine embryonic stem cell derived osteogenic cells were utilized to test the
      suitability of these scaffolds in tissue engineering applications. The seeded
      cells were able to colonize and grow in these scaffolds. Based on the overall
      consideration of morphology, mechanical performance, and ability for cell
      attachment and proliferation, the scaffolds with approximately 30-40% PCL appear
      to be an appropriate choice for tissue engineering. These findings suggest that
      sacrificial compression-molding of PCL-PEO powder blends can be used in the
      generation of biocompatible scaffolds with controllable porosity and pore size
      and may be used for in vitro tissue engineering applications.

PMID- 16292760
TI  - Retrieval analysis of clinical explanted vena cava filters.
AB  - Vena cava filters are the most commonly used mechanical devices to prevent
      pulmonary embolism. A retrievable permanent filter has been available since 1999.
      That has allowed the direct study of thrombi captured in humans and the punctual
      interaction of blood and device at long and short term. Through traditional
      histologic methods, captured thrombi and the tissues formed around the filter
      were observed. An innovative environmental scanning electron microscopy technique
      allowed detection of micro- and nanosized foreign bodies inside thrombi and
      tissues, and chemical analysis could be carried out by means of energy dispersive
      spectroscopy. All specimens contained different quantities of foreign debris
      ranging from few tens of microns to 50 nanometers; their chemistry was not
      homogeneous when patients were compared, and also differed considerably within
      the same filter. The constant presence of debris deeply embedded in all thrombi
      observed may mean that they are the cause that triggered the formation of those
      thrombi as a result of the interaction between foreign bodies and blood
      components.

PMID- 16292761
TI  - A novel method to obtain microtensile specimens minimizing cut flaws.
AB  - Cutting procedures conventionally used for microtensile specimens' preparation
      induce mechanical stress and attrition, leading to cracks in dental structure.
      Enamel is mainly affected due to its high module of elasticity and brittleness.
      As an alternative to the conventional diamond saw, a diamond wire was used for
      cutting. The two techniques were compared in efficacy in the preparation of two
      different sample shapes. Forty human molars, flattened in dentin or enamel, were
      used for sample preparation. After bonding procedures, resin block was built
      incrementally. Half of the teeth were cut using a diamond disc and the other half
      using a diamond wire, obtaining slabs and stick-shaped specimens. Slabs were then
      shaped to obtain hourglass samples. Five samples from each subgroup were randomly
      selected for Scanning electron microscopy (SEM) analysis. Remaining samples
      underwent microtensile test and the results were analyzed, including/excluding
      premature failures (pf), with three-way ANOVA and Tukey test, performed
      separately, by substrate. On dentin, only the exclusion of pf showed a
      significant higher bond strength values than when pf were included (p < 0.05);
      however, on enamel, all factors (equipment, shape and including/excluding pf) had
      a significant effect on bond strength (p<0.05). The most remarkable finding from
      SEM was the incidence of specimens' cracks and defects when diamond blade was
      used. Scratches and cracks in the hourglass-shaped specimens were also detected.
      In both cases, enamel was more affected than dentin.

PMID- 16292762
TI  - UV-embossed microchannel in biocompatible polymeric film: application to control
      of cell shape and orientation of muscle cells.
AB  - This article shows that ultra violet (UV) micro-embossing can be successfully
      used for fabricating biocompatible micropatterned films with microchannels
      separated by high aspect ratio microwalls. Eight series of micropatterns were
      investigated; the width of the microwall was either 10 or 25 microm and that of
      the microchannel either 40, 80, 120, or 160 microm. The material investigated was
      principally polyurethane diacrylate. The UV-embossed micropattern was extracted
      with methanol, converting the micropatterns from cytotoxic to biocompatible. The
      typical UV embossing method was modified by using a marginally adhesive polyester
      substrate, which facilitates demolding but is removable before methanol
      extraction to avoid fragmentation of the embossed micropatterns. The effect of
      the micropatterns on A7r5 smooth muscle cells and C2C12 skeletal muscle cells was
      investigated. The dimensions of both channel and wall have significant effects on
      the elongation of both muscle cells. In the narrower 40-microm channel, the C2C12
      cells merged together to form myofibers. These results indicate that UV-embossed
      micropatterns may present a useful scaffold for in vitro cell shape and
      orientation control needed in vascular and muscle tissue engineering.

PMID- 16292763
TI  - Characterization of human primary osteoblast response on bioactive glass (BaG 13
      93)- coated poly-L,DL-lactide (SR-PLA70) surface in vitro.
AB  - Bioabsorbable polylactide-based polymers are commonly used for bone
      reconstruction. Although these polymers have proven successful in many
      applications, they do not have the capacity to induce osteoconduction. Therefore,
      several strategies have been developed to manufacture osteoconductive polylactide
      based composites. In this study, we have investigated in vitro response of human
      primary osteoblasts for self-reinforced poly-L,DL-lactide 70/30 (SR-PLA70) plates
      coated with spheres of bioactive glass 13-93 (SR-PLA70 + BaG). Osteoblasts were
      cultured on SR-PLA70 and SR-PLA70 + BaG plates for 2, 7, or 14 days. By day 7,
      both materials induced a reduction in total cell population. However, by day 14
      the proliferative response of osteoblasts on SR-PLA70 + BaG surface was such that
      the cell population had regained similar levels as that of day 2 controls.
      Alkaline phosphatase activity was higher on SR-PLA70 at day 7 but declined to
      control levels by day 14. There were no significant time-dependent variations in
      alkaline phosphatase activity on SR-PLA70 + BaG. After in vitro hydrolysis for 7
      days, the elemental analysis of SR-PLA70 + BaG surface showed the presence of
      mineral precipitates that were confirmed as crystalline hydroxyapatite. This was
      accompanied by osteoblast spreading, protrusions of microvilli adhered to BaG 19
      39 surface, cuboidal phenotype and cell surface associated formation of
      hydroxyapatite microspheres. In conclusion, the SR-PLA70 + BaG composite is
      capable of inducing a proliferative response of human primary osteoblasts, and
      appears to support the development of mature osteoblast phenotype. Therefore, the
      SR-PLA70 + BaG composites appear as promising osteoconductive scaffold candidates
      for reconstruction and regeneration of bone matrix.

PMID- 16292764
TI  - In vitro wear of resin-based materials--simultaneous corrosive and abrasive wear.
AB  - The aim of this study was to evaluate the wear of resin-based materials caused by
      the association of abrasive and corrosive processes. Twenty specimens were
      prepared for each material, cast in epoxy in acrylic rings, polished, and
      profiled with an MTS 3D Profiler. Antagonists were made from deciduous molars.
      Specimens were distributed into eight groups (n = 10), according to the material
      (Filtek Supreme, Point 4, Dyract AP, and Fuji II LC) and the type of slurry
      (neutral and acidic), and then cycled 100,000 times in the OHSU oral wear
      simulator. The specimens were cleaned and reprofiled. Volume loss and maximum
      depth were determined. ANOVA and Tukey's test were used for data analysis (p <
      0.05). The area of the wear facet on the antagonist was also measured. Composites
      displayed less wear than the compomer and the resin-modified glass ionomer.
      Significant differences also were found for cusp wear, with a significant
      positive correlation shown between cusp and material wear. The acidic slurry
      significantly increased the wear of the materials compared to the neutral slurry.
      Exposure to acidic slurry accelerated the wear of resin-based materials.

PMID- 16292765
TI  - Advanced nanocomposite materials for orthopaedic applications. I. A long-term in
      vitro wear study of zirconia-toughened alumina.
AB  - The use of ceramic-on-ceramic (alumina- and zirconia-based) couplings in hip
      joint prostheses has been reported to produce lower wear rates than other
      combinations (i.e., metal-on-polyethylene and ceramic-on-polyethylene). The
      addition of zirconia into an alumina matrix (zirconia-toughened alumina, ZTA) has
      been reported to result in an enhancement of flexural strength, fracture
      toughness, and fatigue resistance. The development of new processing routes in
      nonaqueous media has allowed to obtain high-density ZTA nanocomposites with a
      very homogeneous microstructure and a significantly smaller and narrower particle
      size distribution of zirconia than conventional powder mixing methods. The aim of
      the present study was to set up and validate a new ZTA nanocomposite by testing
      its biocompatibility and wear behavior in a hip-joint simulator in comparison
      with commercial alumina and experimental alumina specimens. The primary
      osteoblast proliferation onto ZTA nanocomposite samples was found to be not
      significantly different from that onto commercial alumina samples. After 7
      million cycles, no significant differences were observed between the wear
      behaviors of the three sets of cups. In this light, it can be affirmed that ZTA
      nanocomposite materials can offer the option of improving the lifetime and
      reliability of ceramic joint prostheses.

PMID- 16292766
TI  - Characterization of functionally graded hydroxyapatite/titanium composite
      coatings plasma-sprayed on Ti alloys.
AB  - Bioceramic coatings like hydroxyapatite (HA) have shown promising bioactive
      properties in load-bearing implant applications. The aim of this work is to
      deposit functionally graded HA/Ti layers consisting of an underlying Ti bond
      coat, the alternating layer, and an HA top-layer on Ti6Al4V substrates using
      plasma spray to improve the coating-substrate interface properties. The
      alternating layers were created by means of changing the feeding rate and input
      power of Ti and HA powders, which gradually decrease Ti content with increasing
      depth from the Ti bond-coat. The major consideration is to examine the stability
      of the graded coatings. Experimental results indicated that surface chemistry and
      morphology of the graded coatings were similar to those of monolithic HA
      coatings. The bond strength values of the as-sprayed graded coatings were much
      superior to those of monolithic HA coatings. The cyclic fatigue did have a
      statistically significant effect on bond strength of monolithic HA coatings, with
      a decrease of 23%. However, the graded coatings were able to survive 1 million
      cycles of loading in air without significantly reduced bond strength. The in
      vitro electrochemical measurement results also indicated that the graded coatings
      had a more beneficial and desired behavior than monolithic HA coatings after
      fatigue.

PMID- 16292767
TI  - The biocompatibility of silk fibroin films containing sulfonated silk fibroin.
AB  - Sulfonation reaction may be an effective method for preparation of heparin-like
      materials. However, no sulfonated polymer based on protein backbone was used for
      improving the blood compatibility of biomaterials. In this study, the
      biocompatibility of new kind of composite materials films obtained by blending
      silk fibroin (SF) with sulfonated silk fibroin (SSF) was evaluated. The
      anticoagulant activity was characterized with prothrombin time (PT), activated
      partial thromboplastin time (APTT), and thrombin time (TT), which all increased
      remarkably, the clot times exceeded the measurement limit of clot detection
      instrument. Its platelet adhesion was also investigated as another parameter of
      blood compatibility. The cell compatibility of composite films was evaluated
      through cell morphologies on the films and cell viability by methyl thiazolyl
      tetrazolium (MTT) assay. Tensile strength and elongation at break of the
      composite films reached to 44.6 MPa and 50.3%, respectively. All these results
      indicated that SF/SSF composite film was a potential material for blood-contact
      materials and tissue engineering matrix.

PMID- 16292768
TI  - An in vitro optimized injectable calcium phosphate cement for augmenting screw
      fixation in osteopenic goats.
AB  - This study reports the proportioning and standardized mixing procedures for
      preparing a hydroxylapatite cement (tetracalcium phosphate and dicalcium
      phosphate) of desired viscosity and mechanical strength reproducibly for
      application in trauma surgery. The behavior and the biomechanical properties of
      the resulting bone cement in screw augmentation were then evaluated in our
      osteopenic goat model. The use of a shaker standardized the mixing procedure. The
      optimal volume of Na2HPO4 used to prepare the injectable cement was 0.45 mL/g,
      with averaged in vitro compressive strength of 48.29 +/- 5.62 MPa. Histology
      showed increasing tightly-coupled bone apposition on the cement surface without
      fibrous encapsulation as observed in the screw-only controls with time in the
      osteopenic goat model. The cement increased the initial screw pull-out force
      (54.7%, p = 0.005) significantly and the energy required to failure (54.7%, p <
      0.05) significantly, and remained higher than the screw-only controls after 3
      months (9.8% and 20.2%, respectively) and 6 months (20.2% and 44.7%,
      respectively). These results imply potential in the prevention of interfacial
      micromotions and subsequent fibrous tissue formation at the implant-bone
      interface resulting in a decreased risk of implant failure. The optimized cement
      in this study may serve as a good candidate for augmenting fixation of
      osteoporotic bone.

PMID- 16292770
TI  - Fine structure and functional morphology of the mouthparts of a male Veigaia sp.
      (Gamasida: Veigaiidae) with remarks on the spermatodactyl and related sensory
      structures.
AB  - Mites of the genus Veigaia are common gamasid inhabitants of forest litter. They
      engage in the peculiar reproductive strategy of podospermy which, along with
      other morphological and behavioral adaptations, involves modification of the
      chelicerae of the relatively rare males into gonopods. Each movable digit is
      provided with an appendage (spermatodactyl) that is involved in sperm transfer.
      We describe the gross anatomy, fine structure, and functional morphology of the
      mouthparts of a male Veigaia species and give ultrastructural details for the
      corniculi, laciniae, preoral cavity, labrum, pharynx, and movable and fixed
      digits. The fine structure of the spermatodactyl is illustrated here for the
      first time in detail. A semischematic reconstruction of the gnathosoma and
      spermatodactyl is provided. The spermatodactyl is totally fused with the movable
      digit and a sperm transfer duct runs along its entire length. This duct starts at
      the adaxial base of the movable digit, continues inside the digit into the tube
      of the spermatodactyl, and finally opens at the distal abaxial surface of the
      spermatodactyl. Several sensory structures associated with the spermatodactyl
      probably provide the male with mechanical and chemical clues.

PMID- 16292769
TI  - Fatigue debonding of the roughened stem-cement interface: effects of surface
      roughness and stem heating conditions.
AB  - The aim of this study was to determine the effects of cyclic loading on the
      debond process of a roughened stem-cement interface used in total hip
      arthroplasty. The specific goals were to assess the effects of two surgeon
      controlled variables (stem heating and degree of stem surface roughness) and to
      determine if an independent finite element-based fracture mechanics model could
      be used to predict the debond response. A clamped cantilever beam geometry was
      used to determine the fatigue debond response of the stem-cement interface and
      was created using an experimental mold that simulated in vivo cementing
      conditions. A second experiment was performed using a torsion-loading model
      representative of the stem-cement-bone composite. For both experiments, two stem
      heating (room temperature and 50 degrees C) and surface roughness conditions
      (grit blasted: Ra = 2.3 and 5.1 microm) were used. Finally, a finite element
      model of the torsion experiment with provision for crack growth was developed and
      compared with the experimental results. Results from both experiments revealed
      that neither stem preheating nor use of a stem with a greater surface roughness
      had a marked effect on the fatigue debond response. There was substantial
      variability in the debond response for all cases; this may be due to microscopic
      gaps at the interface for all interface conditions. The debond rate from the
      finite element simulation (10(-7.31) m/cycle) had a magnitude similar to the
      experimental torsion model (10(-(6.77 +/- 1.25)) m/cycle). This suggests that
      within the context of the experimental conditions studied here that the debond
      response could be assessed using a linear elastic fracture mechanics-type
      approach.

PMID- 16292771
TI  - Urinary calculus fragmentation during Ho: YAG and Er:YAG lithotripsy.
AB  - BACKGROUND AND OBJECTIVES: We tested Ho:YAG and Er:YAG laser ablation of human
      urinary calculi to determine if Er:YAG is a more efficient lithotripsy device.
      STUDY DESIGN/MATERIALS AND METHODS: Ablation efficiency of Ho:YAG and Er:YAG
      lasers was tested at varying energy settings, ranging from the damage threshold
      to clinical energy setting associated with Ho:YAG laser. Stones of known
      composition (calcium oxalate monohydrate (COM), cystine, and uric acid (UA)) were
      irradiated. Crater width, depth, and ablation volumes were determined using an
      optical coherence tomography (OCT). RESULTS: For all stones and energy settings,
      the Er:YAG laser produced deeper craters and larger ablation volumes than Ho:YAG
      laser. The Ho:YAG laser created wider craters during the multiple pulse process
      and the shape of craters was irregular. CONCLUSIONS: The Er:YAG laser is more
      efficient than the Ho:YAG laser for lithotripsy. The deeper craters produced by
      the Er:YAG laser is attributed to the high absorption of energy at its
      wavelength.

PMID- 16292772
TI  - Temperature and gender influences on the hepatic stroma (and associated
      pancreatic acini) of Nile tilapia, Oreochromis niloticus (Teleostei, Cichlidae):
      a stereological analysis by light microscopy.
AB  - The normal organ morphology and function in fishes varies according to several
      natural factors, and such variability is found in liver. Knowledge about the
      normal liver microanatomy is fundamental to pathological evaluation. Even though
      gender and temperature are important factors for modulating morphophysiological
      processes in fishes, their influences on liver stroma are virtually unknown.
      Because temperature- and gender-related changes exist in liver parenchyma, we
      predict both factors should also influence the normal stromal structure. Using
      Nile tilapia as a model, we undertook a study to: 1) establish baseline
      quantitative structural data on the hepatic stroma (and intimately associated
      pancreatic acini); 2) compare data with those available from other species,
      namely, salmonids that do not have a liver with pancreatic acini; and 3) test our
      hypothesis that, within normal healthy limits, the stroma and its structural
      components may vary significantly with temperature and gender. We used 1-year-old
      male and female specimens acclimated to 17 degrees C (breeding noncompatible) and
      27 degrees C (breeding compatible) for 45 days. Basic morphometric fish
      parameters were recorded. After estimation of liver volume, the organ was sliced
      and pieces systematically sampled for light microscopy. Stereology allowed
      estimation of the relative volumes of organ components. The total volumes were
      computed by combining the relative volumes with the total liver volumes. Nile
      tilapia of both genders, held at 17 vs. 27 degrees C, showed structural
      quantitative differences in the relative volumes of stroma and most of its
      components, and in the total volumes of certain stromal elements. The total
      volume of the stroma and of associated pancreatic acini did not differ. We first
      established that, in fishes, the total amount (volume) of liver biliary ducts and
      of eosinophilic granule cells might significantly change (increase and decrease,
      respectively) with a higher acclimation temperature. Indeed, virtually all the
      stereological changes were, essentially, temperature- and not gender-related. At
      27 degrees C, parallel changes in the parenchyma caused a decreased liver volume
      and hepatic-somatic index (HSI). The relative volumetric proportion of stroma vs.
      parenchyma in tilapia is higher than in salmonids. The differences found in this
      study could not be detected with a qualitative approach, thus stressing the
      importance of using stereology for analyzing histological patterns and for
      establishing reliable baseline values in healthy conditions. It was also
      anticipated that in experimental settings with fish the baseline liver stromal
      architecture may be different according to temperature and breeding status; in
      consequence, the effects of the tested variable may also diverge. Our data do not
      fully explain the lower liver volume and HSI at 27 degrees C, thus justifying
      studies on the parenchyma, particularly on cell size and number.

PMID- 16292773
TI  - Computer-based three-dimensional reconstruction of the anatomy of Microhedyle
      remanei (Marcus, 1953), an interstitial acochlidian gastropod from Bermuda.
AB  - Phylogenetic analysis of the highly enigmatic and aberrant acochlidian
      opisthobranch gastropods is mainly hindered by the lack of reliable anatomical
      data. Due to their small size, marine interstitial acochlidian species are not
      suitable for anatomical investigations by dissecting. The tinyness and complexity
      of, e.g., opisthobranch central nervous and reproductive systems make data
      derived from older paraffin-based histology and interpretation by hand-based
      graphical reconstruction questionable. In a former study, a hermaphroditic member
      of the basal acochlidian genus Hedylopsis ("Hedylopsacea") has been examined in
      detail. The present study uses the gonochoric Microhedyle remanei
      (Microhedylidae) as a model organism of the other traditional major acochlidian
      subgroup, the "Microhedylacea." More than 20 specimens with up to 2 mm body
      length were extracted from coarse subtidal sand near Castle Roads, Bermuda
      Islands. Their central nervous, digestive, circulatory, excretory, and genital
      systems were reconstructed three-dimensionally from serial semithin histological
      sections using AMIRA software. The radula was analyzed by SEM. Our specimens
      closely resemble the original description of M. remanei (Marcus, 1953; as Unela)
      from Brazil; apparent differences regarding the number of visceral loop ganglia
      or details of male genitalia are assumed to be due to oversights by the former
      author or because of different ontogenetic stages. Microhedyle remanei differs
      from all congeners due to the lack (vs. presence) of eyes; further distinguishing
      features are discussed. In contrast to members of the hedylopsacean Hedylopsidae,
      Acochlidiidae, and Tantulidae, M. remanei shows a nervous system with numerous
      precerebral accessory "ganglia" that are not differentiated into cortex and
      medulla. While all Microhedylidae previously were thought to lack a heart, M.
      remanei shows a two-chambered heart, as is usual for opisthobranchs. The oocytes
      of M. remanei are yolky and large in relation to body size and suggest
      intracapsular larval development. A comparative microanatomical discussion and
      the distribution of characters within acochlidian taxa indicate that the current
      classification of the Acochlidia does not reflect phylogenetic relationships.
      Detailed structural investigations on further poorly known species are required;
      the computer-based 3D reconstruction of semithin serial sections with AMIRA is
      shown to be an ideal tool for efficient analysis and presentation of the
      microanatomy of small specimens.

PMID- 16292774
TI  - Characterization of two new zebrafish members of the hedgehog family: atypical
      expression of a zebrafish indian hedgehog gene in skeletal elements of both
      endochondral and dermal origins.
AB  - We have characterized two new members of the Hedgehog (Hh) family in zebrafish,
      ihha and dhh, encoding for orthologues of the tetrapod Indian Hedgehog (Ihh) and
      Desert Hedgehog (Dhh) genes, respectively. Comparison of ihha and Type X collagen
      (col10a1) expression during skeletal development show that ihha transcripts are
      located in hypertrophic chondrocytes of cartilaginous elements of the
      craniofacial and fin endoskeleton. Surprisingly, col10a1 expression was also
      detected in cells forming intramembranous bones of the head and in flat cells
      surrounding cartilaginous structures. The expression of col10a1 in both
      endochondral and intramembranous bones reflects an atypical composition of the
      extracellular matrix of the zebrafish craniofacial skeleton. In addition, during
      fin ray regeneration, both ihha and col10a1 are detected in scleroblasts,
      osteoblast-like cells secreting the matrix of the dermal bone fin ray. The
      presence of cartilage markers suggests that the dermal fin ray possesses an
      intermediate phenotype between cartilage and bone.

PMID- 16292775
TI  - Identification and comparative expression analysis of a second wt1 gene in
      zebrafish.
AB  - The Wilms' tumor suppressor gene wt1 encodes a zinc-finger transcription factor
      that plays an important role in the development of the mammalian genitourinary
      system. Mutations in WT1 in humans lead to anomalies of kidney and gonad
      development and cause Wilms' tumor, a pediatric kidney cancer. The inactivation
      of both wt1 alleles in mice gives rise to multiple organ defects, among them
      agenesis of kidney, spleen, and gonads. In zebrafish, an ortholog of wt1 has been
      described that is expressed in the pronephric field and is later restricted to
      the podocytes. Here, we report the existence of a second wt1 gene in zebrafish,
      which we have named wt1b (we named the initial gene wt1a). The overall sequence
      identity of the two Wt1 proteins is 70% and 92% between the zinc-finger regions,
      respectively. In contrast to wt1a, wt1b is expressed from the earliest stages of
      development onward, albeit at low levels. Both wt1a and wt1b are expressed in the
      intermediate mesoderm, with wt1b being restricted to a smaller area lying at the
      caudal end of the wt1a expression domain. In adult fish, high expression levels
      for both genes can be found in gonads, kidney, heart, spleen, and muscle.

PMID- 16292777
TI  - Clinical and technical factors affecting pH and other biomarkers in exhaled
      breath condensate.
AB  - Exhaled breath condensate (EBC) pH appears to be a robust measure of asthma.
      However, the association between EBC pH and clinical factors and airway
      inflammatory markers remains unclear. The objectives of this study were to
      investigate the factors determining EBC pH in asthmatic children, and the
      reproducibility and effects of collection devices on EBC pH in nine healthy,
      nonsmoking adults. EBC was collected once from asthmatic children using
      EcoScreen, and from adults over 3 consecutive days using both RTubes and
      EcoScreen. EBC pH was measured immediately in non-deaerated samples by
      microelectrode pH meter. Concentrations of 8-isoprostane, cysteinyl leukotrienes
      (cys-LT), and leukotriene B4 (LTB4) were measured using enzyme immunoassay.
      Exhaled nitric oxide concentration (FeNO) was measured by chemiluminescence.
      Fifty-eight asthmatics (16 intermittent, 12 mild persistent, and 30 moderate-to
      severe persistent) were recruited. EBC pH was lower among patients with moderate
      to-severe persistent than intermittent asthma (P = 0.046). This marker correlated
      inversely with disease severity score (rho = -0.276, P = 0.036), but not FeNO or
      other EBC biomarkers. Bland-Altman analyses found pH but not other EBC biomarkers
      to be reproducible, which were confirmed by its low coefficient of variation
      (2.7%; range, 0.4-5.2%). There was poor correlation between pH in EBC collected
      by RTube and EcoScreen (rho = 0.059, P = 0.784). Factor analysis selected four
      factors that explained 67.5% of the total variance, and EBC pH clustered with
      both cys-LT and LTB4. In conclusion, our results suggest that pH in non-deaerated
      EBC is influenced by asthma severity in children. EBC pH measurement is
      reproducible, but is dependent on the collection devices used.

PMID- 16292778
TI  - Isolation and characterization of embryonic stem-like cells from canine
      blastocysts.
AB  - Embryonic stem (ES) cells are pluripotent cells with the capacity to generate any
      type of cell. Here we describe the isolation of ES-like cells from canine
      blastocysts. Canine embryos were collected from beagle bitches at day 11-16 of
      first estrus. A total of 80 normal embryos were obtained from 15 dogs. Of the
      embryos, 13 were at the morulae stage, 39 at the blastocyst stage, and 28 at the
      hatched blastocyst stage. The inside of morulae or inner cell masses (ICMs) of
      blastocysts were isolated mechanically, and cultured onto mouse embryonic
      fibroblasts (MEF) as feeder layers. Primary cell colonies were formed in 0%
      (0/13) of morulae, 25.6% (10/39) of blastocysts, and 67.9% (19/28) of hatched
      blastocysts. These colonies were separated either by enzymatic dissociation or by
      mechanical disaggregation. Dissociation with collagenase resulted in immediate
      differentiation, but with mechanical disaggregation these cells remained
      undifferentiated, and two ES-like cell lines (cES1, cES2) continued to grow in
      culture after eight passages. These cells had typical stem cell-like morphology
      and expressed specific markers such as alkaline phosphatase activity, stage
      specific embryonic antigen-1 and Oct-4. These cells formed embryoid bodies (EBs)
      in a suspension culture; extended culture of EBs resulted in the formation of
      cystic EBs. When the simple EBs were cultured on tissue culture plates, they
      differentiated into several types of cells including neuron-like, epithelium
      like, fibroblast-like, melanocyte-like, and myocardium-like cells. These
      observations indicate that we successfully isolated and characterized canine ES
      like cells.

PMID- 16292779
TI  - Polyethylenimine-based antisense oligodeoxynucleotides of IL-4 suppress the
      production of IL-4 in a murine model of airway inflammation.
AB  - BACKGROUND: Interleukin-4 (IL-4) plays a crucial role as an inflammatory mediator
      in allergic asthma via inducing Th2 inflammation and IgE synthesis. To develop an
      effective therapeutic agent which specifically inhibits production of IL-4,
      antisense oligodeoxynucleotides (AS-ODNs) against murine IL-4 mRNA were generated
      and complexed with polyethylenimine (PEI) to improve intracellular delivery.
      METHODS: AS-ODNs were generated against the translation initiation region of
      murine IL-4 mRNA, and complexed with linear PEI. In vitro efficacy of AS-ODNs/PEI
      complexes was tested by measuring IL-4 production in the D10.G4.1 cell line, and
      cytotoxicity was tested by XTT assay. Physicochemical properties of polyplexes
      were examined using atomic force microscopy (AFM) and DNase I protection assay.
      In vivo effects of IL-4 AS-ODNs/PEI complexes were tested in a murine model of
      airway inflammation. IL-4 concentrations in the bronchoalveolar lavage (BAL)
      fluid and circulating IgE levels were measured by ELISA, and histological
      analysis of lung tissues was performed. RESULTS: IL-4 AS-ODNs/PEI complexes were
      spheres with an average diameter of 98 nm and resistant to DNase I-mediated
      degradation. IL-4 AS-ODNs/PEI complexes showed up to 35% inhibition of IL-4
      production in D10.G4.1 cells without causing any toxicity, while naked ODNs gave
      less than 1% reduction. Furthermore, IL-4 AS-ODNs/PEI complexes were effective in
      suppressing secretion of IL-4 (up to 30% reduction) in the BAL fluid in an
      ovalbumin-sensitized murine model of airway inflammation. Circulating IgE levels
      were decreased, and airway inflammation was alleviated by treatment with IL-4 AS
      ODNs polyplexes. CONCLUSIONS: These data demonstrate that complexation of IL-4 AS
      ODNs with PEI provides a potential therapeutic tool in controlling inflammation
      associated with allergic asthma, and further presents an opportunity to the
      development of clinical therapy based on combination of multiple AS-ODNs of
      cytokines and/or signaling effectors involved in Th2 inflammation and
      eosinophilia.

PMID- 16292780
TI  - Asymmetric conjugate addition of organozinc compounds to alpha,beta-unsaturated
      aldehydes and ketones with [2.2]paracyclophaneketimine ligands without added
      copper salts.

PMID- 16292782
TI  - Enantioselective aza-Henry reactions assisted by Zn(II) and N-methylephedrine.

PMID- 16292781
TI  - Fast colorimetric sensing of adenosine and cocaine based on a general sensor
      design involving aptamers and nanoparticles.

PMID- 16292783
TI  - Predictions, synthetic strategy, and isolation of a linear tetrametallic triple
      stranded lanthanide helicate.

PMID- 16292776
TI  - Development of the upper lip: morphogenetic and molecular mechanisms.
AB  - The vertebrate upper lip forms from initially freely projecting maxillary, medial
      nasal, and lateral nasal prominences at the rostral and lateral boundaries of the
      primitive oral cavity. These facial prominences arise during early embryogenesis
      from ventrally migrating neural crest cells in combination with the head ectoderm
      and mesoderm and undergo directed growth and expansion around the nasal pits to
      actively fuse with each other. Initial fusion is between lateral and medial nasal
      processes and is followed by fusion between maxillary and medial nasal processes.
      Fusion between these prominences involves active epithelial filopodial and
      adhering interactions as well as programmed cell death. Slight defects in growth
      and patterning of the facial mesenchyme or epithelial fusion result in cleft lip
      with or without cleft palate, the most common and disfiguring craniofacial birth
      defect. Recent studies of craniofacial development in animal models have
      identified components of several major signaling pathways, including Bmp, Fgf,
      Shh, and Wnt signaling, that are critical for proper midfacial morphogenesis
      and/or lip fusion. There is also accumulating evidence that these signaling
      pathways cross-regulate genetically as well as crosstalk intracellularly to
      control cell proliferation and tissue patterning. This review will summarize the
      current understanding of the basic morphogenetic processes and molecular
      mechanisms underlying upper lip development and discuss the complex interactions
      of the various signaling pathways and challenges for understanding cleft lip
      pathogenesis.

PMID- 16292784
TI  - Study of the hydrophobic cavity of beta-cryptogein through laser-polarized xenon
      NMR spectroscopy.
AB  - The interaction of xenon with beta-cryptogein, a basic 10 kDa protein belonging
      to the elicitin family, has been studied by using dissolved thermal and laser
      polarized gas in liquid-state NMR. 13C and 1H chemical-shift-mapping experiments
      were unfruitful, the proton lines only experienced a slight narrowing but no
      significant frequency variation when the xenon concentration was increased.
      Nevertheless magnetization transfer from hyperpolarized xenon to protons of the
      protein demonstrates an undoubted interaction and enables localization of the
      noble-gas-binding site. Due to the proton-proton cross-relaxation efficiency,
      however, this experiment is subjected to important spin-diffusion. An automatic
      procedure that takes spin-diffusion into account when assigning the protons that
      interact with xenon is then used. The binding site, as defined by 30 Xe--H
      interactions, is situated in the inner core of the protein. The protons that
      interact with xenon border the channel by which sterols are known to enter into
      the cavity. These results support the idea that xenon is a good probe for
      hydrophobic protein regions.

PMID- 16292785
TI  - Dissection of the late steps in aureothin biosynthesis.

PMID- 16292786
TI  - A divergent path of chlorophyll breakdown in the model plant Arabidopsis
      thaliana.

PMID- 16292787
TI  - Destabilization of quadruplex DNA by 8-aminoguanine.

PMID- 16292788
TI  - Synthesis and two-photon photolysis of 6-(ortho-nitroveratryl)-caged IP3 in
      living cells.
AB  - The synthesis of a photolabile derivative of inositol-1,4,5-trisphosphate (IP3)
      is described. This new caged second messenger (6-ortho-nitroveratryl)-IP3 (6-NV
      IP3) has an extinction coefficient of 5000 M(-1) cm(-1) at 350 nm, and a quantum
      yield of photolysis of 0.12. Therefore, 6-NV-IP3 is photolyzed with UV light
      about three times more efficiently than the widely used P(4(5))-1-(2
      nitrophenyl)ethyl-caged IP3 (NPE-IP3). 6-NV-IP3 has a two-photon cross-section of
      about 0.035 GM at 730 nm. This absorbance is sufficiently large for effective two
      photon excitation in living cells at modest power levels. Using near-IR light (5
      mW, 710 nm, 80 MHz, pulse-width 70 fs), we produced focal bursts of IP3 in HeLa
      cells, as revealed by laser-scanning confocal imaging of intracellular Ca2+
      concentrations. Therefore, 6-NV-IP3 can be used for efficient, subcellular
      photorelease of IP3, not only in cultured cells but also, potentially, in vivo.
      It is in the latter situation that two-photon photolysis should reveal its true
      forte.

PMID- 16292789
TI  - Supportive care needs: are patients with lung cancer a neglected population?
AB  - While the unmet supportive care needs are well documented for some groups of
      cancer patients, relatively little is known about the levels and types of needs
      of lung cancer patients. The study aims to compare the levels of lung cancer
      patients' psychosocial needs with those of other cancer patients. A total of
      1,492 consecutive patients in nine major public cancer treatment centres in New
      South Wales, Australia, were invited to participate in the Supportive Care Needs
      Study; 888 completed surveys were received. The mean number of unmet needs (out
      of a maximum of 59) reported by lung cancer patients was 15.6 (95% CI 12.1-19.1),
      compared to 10.9 (95% CI 10.0-11.8) in other cancer patients. The differences
      were mainly due to the fact that lung cancer patients reported a higher mean
      number of unmet psychological needs (7.6 versus 5.0) and physical and daily
      living unmet needs (2.8 versus 1.4), compared to the other cancer patients.
      Having a lung cancer diagnosis was an independent predictor of having a high
      level of psychological need (RR 2.00, 95%CI 1.13-3.56) and daily living need (RR
      2.81, 95%CI 1.60-4.95), together with not being in remission, and receiving the
      cancer diagnosis more than two years previously. The results suggest that
      priority needs to be given to addressing the specific needs of this sub-group of
      cancer survivors.

PMID- 16292790
TI  - Severe systemic hypersensitivity reaction to ibuprofen: a presentation of
      systemic lupus erythematosus.
AB  - We describe the first severe systemic hypersensitivity reaction to ibuprofen in a
      pediatric patient with previously undiagnosed systemic lupus erythematosus (SLE).
      An 11-year-old Thai male presented with fever, rash, altered mental status, and
      hypotension after oral administration of ibuprofen leading to the diagnosis of
      SLE. Re-dosing with ibuprofen resulted in recurrence of presenting symptoms.
      Severe hypersensitivity with hypotension can be a rare consequence of the use of
      ibuprofen in children with collagen vascular disease. When encountered in an
      otherwise healthy child, a high index of suspicion must be maintained for the
      diagnosis of SLE.

PMID- 16292791
TI  - Increased risk of complete congenital heart block in infants born to women with
      hypothyroidism and anti-Ro and/or anti-La antibodies.
AB  - OBJECTIVE: To determine whether the presence of hypothyroidism is associated with
      an increased incidence of neonatal lupus erythematosus (NLE) in infants of
      mothers with anti-Ro autoantibodies. METHODS: The cohort consisted of 87 women
      with anti-Ro antibodies who delivered 102 infants. All infants had a full history
      and physical examination within 12 weeks of birth, electrocardiogram
      (echocardiogram when clinically indicated), complete blood cell count with
      differential, liver function tests, and autoantibody profile. Nine women had
      hypothyroidism and 78 had normal thyroid function. RESULTS: At least one
      manifestation of NLE was seen in 7/9 (78%) infants born to mothers with
      hypothyroidism and 45/78 (58%) infants born to mothers with normal thyroid
      function. Complete congenital heart block (CCHB) was seen in 5/9 (55%) in the
      hypothyroid group and 10/78 (13%) of the normal thyroid function group (p <
      0.005). Mothers with hypothyroidism had a 9-fold increased risk over women with
      normal thyroid function of having a child with CCHB (odds ratio 8.63). Twenty
      seven (31%) of the women were healthy: 4/9 of the hypothyroid and 23/78 of the
      normal thyroid function group. Of the 23 infants born to healthy mothers with
      normal thyroid function, 15/23 (65%) had NLE and 8/23 (35%) of these had CCHB.
      CONCLUSION: Women with hypothyroidism and anti-Ro antibodies were at increased
      risk for delivering a child with CCHB compared to women with antibodies alone,
      irrespective of maternal health. This study indicates that women with
      hypothyroidism should be tested for anti-Ro antibodies, as they may be at risk to
      deliver a child with CCHB.

PMID- 16292792
TI  - Treatment of refractory inflammatory monoarthritis in ankylosing spondylitis by
      intraarticular injection of infliximab.
AB  - OBJECTIVE: We describe a series of cases to evaluate the effect of intraarticular
      infliximab in patients with ankylosing spondylitis (AS) with treatment-resistant
      arthritis, and to consider whether longterm treatment with intravenous infliximab
      could be avoided in these patients. METHODS: Three patients, fulfilling the New
      York criteria for AS, had relapsing arthritis of the knee, despite nonsteroidal
      antiinflammatory drugs, sulfasalazine, and multiple intraarticular (IA)
      injections of corticosteroids. Since the axial disease or other locomotor
      manifestations did not justify administration of systemic tumor necrosis factor-a
      (TNF-a) blocking agents, an IA injection of 100 mg infliximab was administered.
      The primary endpoint was to examine the efficacy and safety of IA injection of
      infliximab in AS patients with therapy-refractory arthritis. Before and 4 weeks
      after IA injection the following variables were evaluated: degree of swelling and
      tenderness of the affected joint, number of cells/mm3 after joint fluid
      examination, Bath Ankylosing Spondylitis Disease Activity Index, erythrocyte
      sedimentation rate, and C-reactive protein. In all 3 cases magnetic resonance
      imaging (MRI) was performed before injection and 4 weeks after injection.
      RESULTS: Clinical and biological variables and the MRI findings clearly improved.
      Remission of the peripheral arthritis was maintained up to 4 months in the first
      patient and up to 3 months in both others. No important side effects were noted.
      CONCLUSION: We observed a beneficial effect of IA infliximab in refractory
      arthritis in patients with AS. This procedure could be considered an effective
      and safe treatment for therapy of refractory monoarthritis in AS and an
      alternative for parenteral TNF-blocking therapy.

PMID- 16292793
TI  - Catalytic, enantioselective alpha-additions of isocyanides: Lewis base catalyzed
      Passerini-type reactions.
AB  - [reaction: see text] The generality of catalytic, enantioselective alpha
      additions of isocyanides to aldehydes has been demonstrated (Passerini-type
      reactions). The catalytic system of silicon tetrachloride and a chiral
      bisphosphoramide (R,R)-1b provided high yields and good to excellent
      enantioselectivities for the addition of tert-butyl isocyanide to a wide range of
      aldehydes (aromatic, heteroaromatic, olefinic, acetylenic, aliphatic). Aqueous
      workup afforded the alpha-hydroxy tert-butyl amides whereas a low-temperature
      methanol quench followed by basic workup afforded the alpha-hydroxy methyl
      esters. The reaction is also successful for other isocyanides, albeit with
      reduced enantioselectivity. Reaction conditions, particularly the rate of
      addition of the isocyanide was found to be crucial for good yields and high
      selectivities.

PMID- 16292794
TI  - Effect of heteroatom insertion at the side chain of 5-alkyl-1H-tetrazoles on
      their properties as catalysts for ester hydrolysis at neutral pH.
AB  - [reaction: see text] Herein we introduce tetrazole and its suitably designed
      derivatives as powerful ester-cleaving reagents. By first performing a detailed
      ab initio computational study, we found that, in the side chain of 5-alkyl-1H
      tetrazoles, introduction of a heteroatom (e.g., N, O, or S at the alpha-position
      of the tetrazole ring) raises the charge on the tetrazole nucleus significantly.
      All calculations have been performed using restricted Hartree-Fock (RHF) and
      hybrid ab initio/DFT (B3LYP) methods employing 6-31G* and 6-31+G* basis sets. To
      estimate the nucleophilicity of these reagents, the charges on conjugate bases of
      various tetrazole derivatives have been calculated using natural population (NBO)
      analysis in gas phase and in water. Free energy of protonation (fep) of the 1H
      tetrazole derivatives (1-7), free energy of solvation, deltaG(aq), and the
      corresponding pKa values have been calculated by self-consistent reaction field
      (SCRF) methods applying the polarized continuum model (PCM). Since the
      calculation indicates that incorporation of heteroatom leads to enhanced
      nucleophilicity in their deprotonated anionic tetrazole forms, a series of 5
      substituted 1H-tetrazole derivatives have been synthesized. These compounds
      indeed catalyze the hydrolysis of p-nitrophenyl diphenyl phosphate (PNPDPP) and p
      nitrophenyl hexanoate (PNPH) efficiently in cationic cetyl trimethylammonium
      bromide (CTABr) micelles at pH 7.0 and 25 degrees C. The pseudo-first-order rate
      constants (k(obs)) were determined for each catalyst against both substrates. The
      experimental and theoretical results show that, to achieve better k(obs) values
      for the cleavage of PNPDPP and PNPH under micellar conditions, charge on the N-
      atom (nucleophile) of conjugate base is important. Replacing the alpha-CH2 in
      alkyl substituent with S (3), NH (4), or O (5) enhances the accumulation of
      charge on N- in conjugate bases of tetrazoles and subsequently increases their
      intrinsic nucleophilic reactivity toward hydrolytic reactions. Significantly
      large rate enhancements were observed for the cleavage of PNPDPP and PNPH at pH
      7.0 in the presence of catalytic system 5/CTABr over background (only CTABr).
      Tetrazole 4 (alpha-isomer) showed 4-5-fold superior reactivity over 6 (beta
      isomer) under identical conditions. Natural charges obtained from NBO analysis
      (B3LYP/6-31+G*) are -0.94 and -0.852 on N- in the conjugate bases of 4 and 6,
      respectively. This also predicts that 4 is a better nucleophile than 6. All the
      newly synthesized tetrazole derivatives in micellar media display true catalytic
      properties by cleaving several fold excess of substrates.

PMID- 16292795
TI  - Synthesis and characterization of 3,5-bis(2-hydroxyphenyl)-1,2,4-triazole
      functionalized tetraaryloxy perylene bisimide and metal-directed self-assembly.
AB  - [structure: see text] New perylene bisimide dyes bearing 3,5-bis(2-hydroxyphenyl)
      1,2,4-triazole receptor units with different spacers have been synthesized and
      characterized. The fluorescence and electronic properties of these compounds have
      been studied. MALDI-TOF, UV-vis, and fluorescence titration experiments proved
      that monotopic perylene bisimide ligands could be assembled into dimmers by
      Fe(III) coordination. The coordination properties of the ditopic perylene
      bisimide ligands have also been studied preliminarily. Furthermore, the SEM
      images indicated that well-defined nanoscale structures could be fabricated by
      self-assembly due to metal ion coordination and pi-pi stacking interactions of
      perylene rings with the help of a proper spacer.

PMID- 16292796
TI  - Synthesis and photochemical properties of stilbenophanes tethered by silyl
      chains. Control of (2pi + 2pi) photocycloaddition, cis-trans photoisomerization,
      and photocyclization.
AB  - [structures: see text] Novel macrocyclic and medium-size stilbenophanes tethered
      by silyl chains were synthesized, and their photochemical and photophysical
      properties were examined. Direct photoirradiation of macrocyclic stilbenophanes
      gave intramolecular photocycloadducts stereoselectively, and the efficiency
      increased with decreasing distance between the two stilbene units. The triplet
      sensitized photoreaction of stilbenophanes caused cis-trans photoisomerization.
      Photoreactions of cis-fixed stilbenophanes under an oxygen atmosphere selectively
      gave phenanthrenophanes. Fluorescence quantum yields increased with the
      introduction of silyl substituents, and hence those of silyl-tethered
      stilbenophanes were larger than that of unsubstituted trans-stilbene.
      Intramolecular excimer emission was observed when the distances between two
      stilbene units in the stilbenophanes were sufficiently small.

PMID- 16292797
TI  - Synthesis, structure, and X-band (9.5 GHz) EPR characterization of the new series
      of pH-sensitive spin probes: N,N-disubstituted 4-amino-2,2,5,5-tetramethyl-3
      imidazoline 1-oxyls.
AB  - [reaction: see text] An approach to the synthesis of new imidazoline nitroxides
      bearing an N',N'-disubstituted amidine group is reported. The approach is based
      on the alkylation of diamagnetic 4-R-amino-1,2,2,5,5-pentamethyl-3-imidazolines
      with bromoacetic acid ethyl ester; the products of alkylation are further
      oxidized to the corresponding nitroxides. The approach allows a variety of
      functional groups to be introduced into the nitroxide molecule structure.
      Alkylation with bromoacetic acid ethyl ester was found to proceed with high
      regioselectivity and afford the products of exo-alkylation. The regiochemical
      assignment is made on the basis of 13C NMR spectra and confirmed by X-ray
      diffraction study. All of the nitroxides synthesized here were shown to have pH
      dependent EPR spectra with pKa ranging from 3.5 to 6.2. For nitroxides 13 bearing
      the carboxylic group remote to the nitroxide moiety, the changes in isotropic
      magnetic parameters of EPR spectra due to reversible deprotonation of the
      carboxylic group were found to be small. For these nitroxides, we demonstrate an
      alternative approach for pKa determination that is based on measuring the peak-to
      peak line width of the EPR spectrum in the presence of the paramagnetic
      broadening agent potassium ferricyanide. The partition coefficients of nitroxides
      in octanol/H2O and octanol/phosphate buffer solution mixtures were measured to
      reveal a range of their lipophilicities.

PMID- 16292798
TI  - Acid/base catalysis by pure water: the aldol reaction.
AB  - [reaction: see text] The mechanism of aldol reactions in pure water has been
      studied with density functional calculations (B3LYP/6-311++G(3d,3p)//B3LYP/6
      31G(d)). The reaction is a three-step process that involves: (1) water
      autoionization generates catalytic hydroxide and hydronium ions, (2) hydroxide
      and hydronium ions rapidly convert donor aldehyde or ketone into enol, and (3) C
      C bond formation and proton transfer occur to give the aldol product. This study
      provides a general basis for understanding acid/base catalysis by pure water.

PMID- 16292799
TI  - Bicyclo[2.2.2]octene-based "crab-like" molecules: synthesis, complexation,
      luminescence properties, and solid-state structures.
AB  - [structure, reaction: see text] The U-shaped, multifunctionalized tetraetheno
      bridged dicyclopenta[b,i]anthracenediol 10 was synthesized to serve as a platform
      molecule. The molecule was prepared from the Diels-Alder adduct 5a of
      tricycloundecatriene 3 and bicyclo[2.2.2]octene-fused p-benzoquinone 4.
      Functionalization of 10 to construct crab-like molecules was achieved via the
      base-promoted bis-O-alkylation of two endo-oriented hydroxyl groups at termini in
      10 with the following alkyl halides: allyl, propagyl, and benzyl bromides; 1
      bromo- and 1-iodo-4-(bromomethyl)benzene; 9-(bromomethyl)anthracene; 1
      (bromomethyl)pyrene; and isomeric bromomethylpyridines. Single-crystal X-ray
      structures were obtained for bis-phenyl (21) and bis-pyrenyl (25) crabs, and for
      the silver(I) complex (32 and 33) crabs. The silver(I) complex 32 from bis-o
      pyridyl crab 30 is a [2+2] dimeric dimetallocyclophane, and 33 from bis-m-pyridyl
      crab 29 is a [1+1] metallo-bridged cyclophane. The self-assembled intramolecular
      pi-stacking of pyrenyl rings in 25 with an interplanar distance of 3.40 A and the
      consequent pi-pi interactions were revealed by the X-ray crystal structure and
      its luminescence property.

PMID- 16292801
TI  - Ketene-ketenimine rearrangements in the gas phase and in polar media. 1,3
      Migration intermediates and sequential transition states.
AB  - [reaction: see text] Calculations of the activation barrier for the 1,3-shifts of
      substituents X in alpha-imidoylketenes 1 (HN=C(X)-CH=C=O), which interconverts
      them with alpha-oxoketenimines 3 (HN=C=CH-C(X)=O) via a four-membered cyclic
      transition state TS2 have been performed at the B3LYP/6-311+G(3df,2p)//B3LYP/6
      31G* level. Substituents with accessible lone pairs have the lowest activation
      barriers for the 1,3-shift (halogens, OR, NR2). The corresponding activation
      barriers for the alpha-oxoketene-alpha-oxoketene rearrangement of 4 via TS5 are
      generally lower by 1-30 kJ/mol. A polar medium (acetonitrile, epsilon = 36.64)
      was simulated using the polarizable continuum (PCM) solvation model. The effect
      of the solvent field is a reduction of the activation barrier by an average of 12
      kJ/mol. In the cases of 1,3-shifts of amino and dimethylamino groups, the
      stabilization of the transition state TS2 in a solvent field is so large that it
      becomes an intermediate, Int2, flanked by transition states (TS2' and TS2'') that
      are due primarily to internal rotation of the amine functions, and secondarily to
      the 1,3-bonding interaction. In the case of the alpha-oxoketene-alpha-oxoketene
      rearrangement of 4, there is a corresponding intermediate Int5 for the 1,3-amine
      shift already in the gas phase.

PMID- 16292800
TI  - Highly selective colorimetric and electrochemical Pb2+ detection based on TTF-pi
      pyridine derivatives.
AB  - [reaction: see text] The pyridineethenyl-substituted tetrathiafulvalene (TTF)
      compounds, 4-(4-pyridineethenyl)tetrathiafulvalene (1a) and 4,4'(5')-[bis-(4
      pyridineethenyl)]tetrathiafulvalene (2a) together with the styryl-substituted TTF
      compounds, 4-styryltetrathiafulvalene (1b) and 4,4'(5')-bis
      styryltetrathiafulvalene (2b), have been designed and synthesized. All these
      compounds exhibit strong absorption bands in the range of 370 to 550 nm, which
      are assigned to the intramolecular charge-transfer transition from the HOMO in
      TTF to the LUMO in the pyridyl or phenyl group. Compared to compounds 1b and 2b,
      the pyridineethenyl-substituted TTF compounds 1a and 2a show remarkable sensing
      and coordinating properties to Pb2+. With the addition of micromolar
      concentrations of Pb2+ to the solution, 1a or 2a displays dramatic changes in the
      UV-vis absorption spectrum, 1H NMR spectrum, and redox property.

PMID- 16292803
TI  - Crystalline-state Z,E-photoisomerization of a series of (Z,E,Z)-1,6-diphenylhexa
      1,3,5-triene 4,4'-dicarboxylic acid dialkyl esters. Chain length effects on the
      crystal structure and photoreactivity.
AB  - [reaction: see text] Crystalline-state Z,E-photoisomerization of a series of
      (Z,E,Z)-1,6-diphenylhexa-1,3,5-triene 4,4'-dicarboxylic acid dialkyl (R) esters
      [(Z,E,Z)-1a, R = Me; (Z,E,Z)-1b, R = Et; (Z,E,Z)-1c, R = n-Pr; (Z,E,Z)-1d, R = n
      Bu] was investigated. All Z,E,Z isomers underwent one-way isomerization to the
      corresponding E,E,E isomers. The reaction efficiency was strongly enhanced as the
      length of the alkyl chain increased. Single-crystal X-ray analyses of (Z,E,Z)-1a
      d showed that the alkyl chain part of the crystals became larger as the chain
      length increased. The conformational flexibility of the alkyl chains made the
      large change in the triene geometry in the lattice possible, leading to the
      enhancement of the photoreactivity in the crystalline state.

PMID- 16292802
TI  - Glycosyl disulfides: novel glycosylating reagents with flexible aglycon
      alteration.
AB  - [reaction: see text] Glycosyl disulfides have been shown for the first time to be
      effective glycosyl donors. Glucosylation and galactosylation of a panel of
      representative alcohol acceptors allowed the formation of 28 simple glycosides,
      disaccharides, and glycoamino acids in yields of up to 90%. As well as providing
      a novel class of effective glycosyl donors, the ability to easily alter the
      nature of the aglycon and the ability to differently activate donors that differ
      only in their aglycon simply through altering conditions lends glycosyl disulfide
      donors to their use in latent-active reactivity tuning strategies.

PMID- 16292804
TI  - Adducts of thianthrene- and phenoxathiin cation radical tetrafluoroborates to 1
      alkynes. Structures and formation of 1-(5-thianthreniumyl)- and 1-(10
      phenoxathiiniumyl)alkynes on alumina leading to alpha-ketoylides and alpha
      ketols.
AB  - [structure: see text] Thianthrene cation radical tetrafluoroborate (Th*+ BF4(-))
      added to the terminal alkynes 1-pentyne, 1-hexyne, 1-heptyne, 1-octyne, 1-nonyne,
      and 1-decyne to form trans-1,2-bis(5-thianthreniumyl)alkene tetrafluoroborates (1
      6). Similarly, addition of phenoxathiin cation radical tetrafluoroborate (PO*+
      BF4(-)) to the same alkynes gave 1,2-bis(10-phenoxathiiniumyl)alkene
      tetrafluoroborates (7-12). The trans configuration of two of the adducts (1 and
      4) was shown with X-ray crystallography. When solutions of 1-6 in chloroform were
      stirred with activated alumina, cis elimination of a proton and thianthrene (Th)
      occurred with the formation of 1-(5-thianthreniumyl)alkyne tetrafluoroborates (1a
      6a). Similar treatment of 8-12 caused elimination of a proton and phenoxathiin
      (PO) with formation of 1-(10-phenoxathiiniumyl)alkene tetrafluoroborates (8a
      12a). Stirring of 1a-6a with alumina for short periods of time caused their
      conversion into 5-[(alpha-keto)alkyl]thianthrenium ylides (1b-6b) and alpha
      ketols, RC(O)CH2OH (1c-6c).

PMID- 16292805
TI  - Enantioselective syntheses of trans-3,4-difluoropyrrolidines and investigation of
      their applications in catalytic asymmetric synthesis.
AB  - [reaction: see text] Asymmetric syntheses of enantiopure trans-3,4
      difluoropyrrolidines have been prepared by the introduction of fluorine at both
      centers in a single operation; asymmetric epoxidations and additions to
      benzaldehyde were conducted using catalysts whose chirality depends on
      organofluorine asymmetry.

PMID- 16292806
TI  - Novel synthesis, properties, and NAD+-NADH type redox ability of 1,3
      dimethylcyclohepta[4,5]pyrrolo[2,3-d]pyrimidine- 2,4(1,3h)-dionylium ions
      annulated with additional pyrrolo[2,3-d]pyrimidine-1,3(2,4h)-dione and furan
      analogue, and their hydride adducts.
AB  - [reaction: see text] A convenient preparation of novel cations 11a,b+ x BF4(-)
      and 12a,b+ x BF4(-), which are derived from annulation of the 1,3
      dimethylcyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1,3H)-dionylium ion with
      additional pyrrolo[2,3-d]pyrimidine-1,3(2,4H)-dione and a furan analogue, was
      accomplished by a novel oxidative cyclization of 1,7-dihydro-7-[1',3'-dimethyl
      2',4'(1',3'H)-dioxo-6'-(phenylamino)-pyrimidin-5'-yl]-1,3-dimethyl-10
      phenylcyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1,3H)-dione 9 and its furan
      analogue by using DDQ or photoirradiation under aerobic conditions. Structural
      characteristics of 11a,b+ and 12a,b+ were clarified on inspection of the UV-vis
      and NMR spectral data as well as X-ray crystal analyses. The stability of cations
      11a,b+ and 12a,b+ is expressed by the pK(R+) values that were determined
      spectrophotometrically to be 10.7-12.6. The electrochemical reduction of 11a,b+ x
      BF4(-) and 12a,b+ x BF4(-) exhibited reduction potential at -0.93 to -1.00 (V vs
      Ag/AgNO3). The first reduction potential of 11a+ was reversible due to steric
      hindrance of two phenyl groups. The photoinduced oxidation reaction of 11a,b+ x
      BF4(-) and 12a,b+ x BF4(-) toward some amines under aerobic conditions was
      carried out to give the corresponding imines (isolated by converting to the
      corresponding 2,4-dinitrophenylhydrazones) with the recycling numbers of 0.6
      30.3. Furthermore, as an example of the NAD+-NADH models, the reduction of a
      pyruvate analogue and some carbonyl compounds with the hydride-adduct of 11a+ x
      BF4(-) was accomplished for the first time to give the corresponding alcohol
      derivatives.

PMID- 16292807
TI  - Synthesis and protein degradation capacity of photoactivated enediynes.
AB  - [structure: see text] The viability of proteins as targets of thermally and
      photoactivated enediynes has been confirmed at the molecular level. Model studies
      using a labeled substrate confirmed the efficacy of atom transfer from diyl
      radicals produced from enediynes to form captodatively stabilized carbon centered
      aminoacyl radicals, which then undergo either fragmentation or dimerization. To
      exploit this finding, a family of enediynes was developed using an intramolecular
      coupling strategy. Derivatives were prepared and used to target specific
      proteins, showing good correlation between affinity and photoinduced protein
      degrading activity. The findings have potential applications in the design of
      artificial chemical proteases and add to our understanding of the mechanism of
      action of the clinically important enediyne antitumor antibiotics.

PMID- 16292808
TI  - Conformationally constrained beta-amino acid derivatives by intramolecular [2 +
      2]-photocycloaddition of a tetronic acid amide and subsequent lactone ring
      opening.
AB  - [reaction: see text] The N-Boc-protected N-3-alkenyltetronic acid amides 9 and 12
      were prepared from tetronic acid bromide (7) and the corresponding amines 6 and
      10 by nucleophilic substitution and subsequent acylation in 71% and 39% overall
      yield. They underwent an intramolecular [2 + 2]-photocycloaddition upon direct
      irradiation (lambda = 254 nm) to yield diastereoselectively the strained lactones
      15 (76%) and 16 (91%) with a 2-azabicyclo[3.2.0]heptane core. In attempts to
      defunctionalize the 1-hydroxymethyl substituent of the 2-azabicyclo[3.2.0]heptane
      skeleton, lactone 15 was converted into mesylate 18 (74% overall yield).
      Intermolecular substitution reactions on this mesylate, however, proceeded
      sluggishly or failed completely. Lactone 15 could be opened reductively (Dibal-H)
      or by substitution with benzylamine to the N-Boc-protected 2
      azabicyclo[3.2.0]heptanes 21 (71%) and 22 (81%). Conformationally constrained
      beta-amino acid derivatives were obtained by quantitative N-Boc deprotection of
      photocycloaddition product 15, followed by N-functionalization and subsequent
      lactone ring opening. The N-functionalization was conducted by acylation (to 24
      26), alkylation (to 27), tosylation (to 28), and isocyanate addition (to 30). The
      reactions proceeded in yields of 70-84%. Lactone ring opening reactions were
      conducted with amines to establish the suitability of this process for library
      synthesis. As an example, the tripeptide 38 was obtained from photocycloaddition
      product 15 in an overall yield of 51%.

PMID- 16292809
TI  - Investigation of nonspecific effects of different dyes in the screening of
      labeled carbohydrates against immobilized proteins.
AB  - [structure: see text] Carbohydrates play an important role in life processes, and
      combinatorial chemistry can provide useful sources of thousands of synthetic
      carbohydrates as potential ligands for biological receptors. To accelerate the
      detection of positive hits arising from specific interactions between a
      carbohydrate and a protein, the use of fluorescent dyes can serve as a reliable
      detecting tool. A study of labeled carbohydrates to lectins conjugated to a solid
      support shows that succinimidyl 6-(N-(7-nitrobenz-2-oxa-1,3-diazol-4
      yl)amino)hexanoate (NBD-X) dye provides by far the lowest level of nonspecific
      interaction with immobilized protein. This observation is in stark contrast with
      the commonly used labeling reagents constituted of charged and aromatic groups,
      for instance, FITC and TAMRA dyes.

PMID- 16292810
TI  - Inherently chiral uranyl-salophen macrocycles: computer-aided design and
      resolution.
AB  - [structure: see text] A flipping motion rapidly inverts the bent structure of
      uranyl-salophen compounds and, consequently, causes fast enantiomerization of
      nonsymmetrically substituted derivatives. This process has been previously slowed
      by introducing bulky substituents in the imine bond region. Since the resulting
      complexes dissociate upon chromatographic treatment, an alternative approach to
      the design and synthesis of robust, nonflipping uranyl-salophen compounds is here
      described. Such an approach is based on the idea that the flipping motion would
      be blocked by connecting the para positions with respect to the phenoxide oxygens
      by means of polymethylene bridges of suitable length. Analysis of a number of
      uranyl-salophen compounds by molecular mechanics, while showing that bulky
      substituents in the imine bond region cause severe distortions of the ligand
      backbone, suggested that the best chain lengths are those that fit the gap
      between the phenoxide rings without altering the natural geometry of the parent
      uranyl-salophen compound. Calculations showed that such chains are those composed
      of 12 and 13 methylene units. Accordingly, chiral uranyl-salophen macrocycles
      bridged with 12- and 13-methylene chains were synthesized in fairly good yields
      and resolved by chiral HPLC.

PMID- 16292811
TI  - Stereoselective total synthesis and absolute configuration of the natural
      decanolides (-)-microcarpalide and (+)-lethaloxin. Identity of (+)-lethaloxin and
      (+)-pinolidoxin.
AB  - [reaction: see text] Convergent, stereoselective syntheses of the
      pharmacologically active, naturally occurring lactones (-)-microcarpalide and (+)
      lethaloxin have been achieved from the commercially available, chiral reagents
      (R)-glycidol, (S,S)-tartaric acid, and d-ribose as the starting materials. These
      syntheses have further served to establish the hitherto unknown absolute
      configuration of (+)-lethaloxin and to show its identity with (+)-pinolidoxin.

PMID- 16292812
TI  - Progressive systematic underestimation of reaction energies by the B3LYP model as
      the number of C-C bonds increases: why organic chemists should use multiple DFT
      models for calculations involving polycarbon hydrocarbons.
AB  - [reaction: see text] Computational studies of three different reaction types
      involving hydrocarbons (homolytic C-C bond breaking of alkanes, progressive
      insertions of triplet methylene into C-H bonds of ethane, and [2+2] cyclizations
      of methyl-substituted alkenes to form polymethylcyclobutanes) show that the B3LYP
      model consistently underestimates the reaction energy, even when extremely large
      basis sets are employed. The error is systematic and cumulative, such that the
      reaction energies of reactions involving hydrocarbons with more than 4-6 C-C
      bonds are predicted quite poorly. Energies are underestimated for slightly and
      highly methyl-substituted cyclic and acyclic hydrocarbons, so the errors do not
      arise from structural issues such as steric repulsion or ring strain energy. We
      trace the error associated with the B3LYP approach to its consistent
      underestimation of the C-C bond energy. Other DFT models show this problem to
      lesser extents, while the MP2 method avoids it. As a consequence, we discourage
      the use of the B3LYP model for reaction energy calculations for organic compounds
      containing more than four carbon atoms. We advocate use of a collection of pure
      and hybrid DFT models (and ab initio models where possible) to provide
      computational "error bars".

PMID- 16292813
TI  - Bridging of bipyridine units by phenylphosphine links: linear and cyclic
      oligomers and some acid derivatives.
AB  - [structures: see text] Reaction of 6,6'-dibromo-2,2'-bipyridine with
      phenylphosphine under palladium-promoted cross-coupling conditions provides a
      variety of linear oligomers bearing two reactive bromo substituents as well as a
      cyclic dimer, characterized by X-ray crystallography, in which the bipyridine
      units are constrained to a cis configuration by two phenylphosphine oxide
      bridges. Derivatives of the linear species containing both carboxylate and
      phosphonate substituents are readily obtained.

PMID- 16292814
TI  - Monomers for preparation of amide-linked RNA: asymmetric synthesis of all four
      nucleoside 5'-azido 3'-carboxylic acids.
AB  - [reaction: see text] Recent discovery of RNA interference as an efficient and
      naturally occurring mechanism of gene regulation has reinvigorated the interest
      in chemically modified RNA. For potential in-vivo applications small interfering
      RNAs require chemical modifications to fine-tune the thermal stability and
      increase the cellular delivery and potency and in vivo half-life of the RNA
      duplexes. From this perspective, amides as neutral and hydrophobic
      internucleoside linkages in RNA are highly interesting modifications for RNA
      interference. Amides are remarkably good mimics of the phosphodiester backbone of
      RNA and can be prepared using a relatively straightforward peptide coupling
      chemistry. However, the progress in the field has been hampered by the shortage
      of efficient methods to synthesize the monomeric building blocks for such
      couplings, the nucleoside amino acid equivalents. Herein, we report
      enantioselective synthesis of 5'-azido 3'-carboxylic acid derivatives of all four
      natural ribonucleosides. The key transformations in our synthesis are a double
      asymmetric ene reaction and a stereoselective iodolactonization that form the
      basic carbon skeleton of the modified ribose. Standard nucleoside synthesis is
      followed by a short and highly efficient protecting group manipulation to give
      the enantiomerically pure (>98%) title compounds in 9-10 steps and 15-19% overall
      yields starting from small achiral molecules. The present results are a
      significant improvement over our first-generation racemic synthesis and compare
      favorably with the previously reported synthesis from nucleoside and carbohydrate
      precursors.

PMID- 16292815
TI  - The synthesis and preliminary biological evaluation of a novel steroid with
      neurotrophic activity: NGA0187.
AB  - [structure, reaction: see text] A full account of the total synthesis of
      neurotrophic compound NGA0187 is provided. A key feature of the synthesis
      involved the direct selective oxidation of 6alpha,7beta-diol to install the
      unusual 6,7-ketol moiety and stereoselective conjugate addition of vinyl cuprate
      to enone. A preliminary evaluation of its ability to stimulate the neurite
      outgrowth was also evaluated with PC12 cell.

PMID- 16292816
TI  - Synthesis and properties of new glucocationic surfactants: model structures for
      marking cationic surfactants with carbohydrates.
AB  - [reaction: see text] In this work, we report the synthesis of a new series of
      glucocationic surfactants, a class of surfactants we introduced very recently.
      The preparation of the surfactants is based on the synthesis of the 2-bromoethyl
      2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside, whose preparation was studied in
      order to improve yields and stereoselectivity of this key intermediate. These
      glucocationic amphiphiles were prepared and studied as a model of cationic
      surfactants marked with a carbohydrate moiety. The use of carbohydrates as
      markers on cationic lipids was recently introduced to induce recognition by
      specific receptors, present on the surface of cell membranes. The chemicophysical
      characterization of these model structures can give more insight on the
      aggregation behavior. Conductivity and surface tension measurements were
      performed in order to characterize the compounds from the amphiphilic point of
      view. The results showed a different effect of the glucosidic moiety on the cmc
      value with respect to the glucopyridinium cationic surfactants. The surfactants
      also showed the tendency to form premicellar aggregates in solution when the
      hydrophobicity is raised.

PMID- 16292818
TI  - Supramolecular incorporation of fullerenes on gold surfaces: comparison of C60
      incorporation by self-assembled monolayers of different calix[n]arene (n = 4, 6,
      8) derivatives.
AB  - [reaction: see text] Two new calix[6]arene derivatives 3 and 4 in a 1,4-anti
      conformation and one calix[8]arene derivative 5 were synthesized. SAMs of
      calix[n]arene (n = 4, 6, 8) derivatives 1-5 were formed on gold bead electrodes.
      Cyclic voltammetry with Ru(NH3)6(3+/2+) as a redox probe, together with impedance
      spectroscopy and reductive desorption, indicates that SAMs of 5 have a higher
      coverage than those of 3 and 4 due to the presence of hydrogen bonding and
      possibly its conformation. Noncovalent immobilization of C60 on gold surfaces was
      achieved with SAMs of calix[8]arene derivative 5 but not with those of 1-4.

PMID- 16292817
TI  - Structure and photochemistry of 18-diazo-1,4,7,10,13,16-hexaoxacyclononadeca
      17,19-dione and its sodium and potassium complexes. Control of the ground-state
      conformation of 2-diazo-1,3-dicarbonyl fragment via host-guest complexation.
AB  - [reaction: see text] The macrocyclic 18-diazo-1,4,7,10,13,16-hexaoxacyclononadeca
      17,19-dione (3-diazo-2,4-dioxo-19-crown-6, 1) readily forms complexes with
      potassium (2, stability constant in methanol is K(K+) = 229 +/- 25 M(-1)) and
      sodium ions (3, K(Na+) = 84.2 +/- 7.9 M(-1) in methanol). According to B3LYP/6
      31G+(d,p) calculations and temperature-dependent 1H NMR spectroscopy, the
      predominant conformation of 1 has a Z,Z arrangement of the diazo and carbonyl
      groups. The X-ray crystal structure analysis showed that the potassium complex
      (2) has the same Z,Z arrangement, while the sodium analogue (2) exists in
      conformation with Z,E geometry of the diazodicarbonyl moiety. Direct 254 nm
      photolysis of diazo compounds 1-3 in methanol results in the formation of 3
      methoxy-2,4-dioxo-19-crown-6 (5), the product of the insertion of corresponding
      alpha,alpha'-dicarbonylcarbene into the O-H bond of the solvent. The triplet
      sensitized photolysis of diazomalonates 1-3 produces 2,4-dioxo-19-crown-6 (6),
      which is apparently formed via the triplet state of the intervening carbene.

PMID- 16292819
TI  - Conformational preferences and enantiodiscrimination of phosphino-4-(1
      hydroxyalkyl)oxazoline-metal-olefin complexes resulting from an OH-metal hydrogen
      bond.
AB  - [reaction: see text] Phosphinooxazolines carrying (1-hydroxy-1-phenyl)methyl and
      (1-methoxy-1-phenyl)methyl substituents in the 4 position of the oxazoline ring
      exhibit contrasting behavior in Pd- and Ir-catalyzed allylic alkylations. Whereas
      catalysts with the methoxy-containing ligand generally provide products with high
      ee's, use of catalysts prepared from the hydroxy-containing ligand results in
      products with low ee's or even racemates. DFT calculations suggest the presence
      of a hydrogen bond with Pd(0) as the proton acceptor in the hydroxy-containing
      olefin-Pd(0) complexes, which induces a conformational change in the ligand,
      leading to different stereoselectivity.

PMID- 16292820
TI  - A practical synthesis of kifunensine analogues as inhibitors of endoplasmic
      reticulum alpha-mannosidase I.
AB  - [reaction: see text] A practical synthesis of the potent class I alpha
      mannosidase inhibitor kifunensine (1) beginning from the inexpensive and readily
      available starting material L-ascorbic acid (15) is described. The protected
      amino-alcohol ((2R,3R,4R,5R)-5-amino-2,3:4,6-diisopropylidenedioxyhexanol, 11)
      served as a key intermediate from which several N-1 substituted kifunensine
      analogues (including N-methyl, N-cyclohexyl, and N-bis(hydroxymethyl)methyl) and
      2-desoxakifunensine analogues (including N-H and N-methyl) were prepared and
      screened for inhibition of human endoplasmic reticulum alpha-mannosidase I (ER
      Man I) and mouse Golgi alpha-mannosidase IA (Golgi Man IA). In addition, several
      pseudodisaccharide kifunensine analogues in which a mannose residue was tethered
      to N-1 of kifunensine via a two-, three-, or four-carbon linker and an affinity
      bound kifunensine analogue were also prepared and evaluated for biological
      activity. While the synthesized N-1 kifunesine analogues were found to be less
      potent inhibitors of Class I alpha-mannosidases than kifuensine itself, the
      bis(hydroxymethyl)methylkifunensine analogue 6 was shown to selectively inhibit
      ER Man I over Golgi Man IA.

PMID- 16292821
TI  - Enantio- and diastereoselective total synthesis of EI-1941-1, -2, and -3,
      inhibitors of interleukin-1beta converting enzyme, and biological properties of
      their derivatives.
AB  - [reaction: see text] The first asymmetric total synthesis of EI-1941-1, -2, and 
      3, inhibitors of the interleukin-1beta converting enzyme (ICE), has been
      accomplished, starting from a chiral epoxy iodoquinone 11, a key intermediate in
      our total synthesis of epoxyquinols A and B. Despite a failure to synthesize the
      inhibitors by our postulated biosynthetic route, we were able to
      diastereoselectively synthesize them via an intramolecular carboxypalladation
      with the key steps being a 6-endo cyclization mode followed by beta-hydride
      elimination. The investigation of the biological properties of EI-1941-1, -2, and
      -3 and their derivatives disclosed them to be potent and effective ICE inhibitors
      with less cytotoxicity than EI-1941-1 and -2 in a cultured cell system.

PMID- 16292823
TI  - Planar-chiral cyrhetrenes for the rhodium-catalyzed asymmetric 1,4-addition and
      the hydrogenation of enamides.
AB  - [reaction: see text] The syntheses of novel cyrhetrenes 7a-c and 8a,b are
      described. These planar-chiral, mono- and diphosphines have been applied as
      ligands in the Rh-catalyzed 1,4-addition reaction to activated olefins and in the
      Rh-catalyzed hydrogenation of enamide 12, giving the corresponding products with
      up to 97 and 93% ee, respectively.

PMID- 16292822
TI  - Preparation and analysis of oligonucleotides containing lesions resulting from
      C5'-oxidation.
AB  - [reaction: see text] Hydrogen atom abstraction from the C5'-position of
      nucleotides in DNA results in direct strand scission. The newly formed 5'-termini
      of the cleaved DNA consists of alkali-labile fragments of the oxidized
      nucleotide. One terminus contains a 5'-aldehyde as part of an otherwise undamaged
      nucleotide (T-al). A second more structurally distinct product that is produced
      in lower yields results from cleavage of the C4'-C5' carbon-carbon bond. The 1,4
      dioxo-2-phosphorylbutane (DOB) is a precursor of the alkylating agent but-2-ene
      1,4-dial. To facilitate studies on these lesions, methods for synthesizing
      oligodeoxynucleotides containing DOB or T-al at their 5'-termini were developed.
      The effects of these lesions on the UV-melting temperatures of duplex DNA, and
      their cleavage labilities were determined. T-al cleaves very slowly (t(1/2) =
      100.7 h), whereas DOB has a half-life at 37 degrees C (pH 7.2) of less than 11 h.
      In addition, DOB forms a stable adduct very efficiently with Tris, which protects
      the abasic site against cleavage.

PMID- 16292824
TI  - De novo asymmetric synthesis of anamarine and its analogues.
AB  - [reaction: see text] The enantioselective synthesis of anamarine has been
      achieved in 21 steps. The route relies on enantio- and regioselective Sharpless
      dihydroxylation of dienoate ester and zinc borohydride reduction to establish the
      C-8-C-11 stereochemistry. A diastereoselective Leighton allylation established
      the desired C-5 stereochemistry. The route has also been used to prepare two
      diastereoisomers of anamarine in 14 steps.

PMID- 16292825
TI  - Practical synthesis of fluorous oxazolidinone chiral auxiliaries from alpha-amino
      acids.
AB  - [reaction: see text] A series of new fluorous-supported oxazolidinone chiral
      auxiliaries has been prepared using a versatile and general five-step pathway,
      starting from readily available chiral alpha-amino acids. The key feature of this
      synthesis is the efficient generation of a suitably active perfluoroalkyllithium
      species. By use of this protocol, the auxiliaries can be obtained in high
      enantiomeric purity and on multigram scales from L-phenylalanine and L-valine
      with overall yields as high as 55%. The new methodology also incorporates
      fluorous solid-phase extraction on the large scale, allowing bulk quantities (up
      to 25 g) of fluorous compounds to be purified from the crude reaction mixture.

PMID- 16292827
TI  - Synthesis and evaluation of 1-deoxy-D-xylulose 5-phosphate analogues as chelation
      based inhibitors of methylerythritol phosphate synthase.
AB  - [structures: see text] A series of 1-deoxy-D-xylulose 5-phosphate (DXP) analogues
      were synthesized and evaluated as inhibitors of E. coli methylerythritol
      phosphate (MEP) synthase. In analogues 1-4, the methyl group in DXP was replaced
      by hydroxyl, hydroxylamino, methoxy, and amino moieties, respectively. In
      analogues 5 and 6, the acetyl moiety in DXP was replaced by hydroxymethyl and
      aminomethyl groups. These compounds were designed to coordinate to the active
      site divalent metal in MEP synthase. The carboxylate (1), methyl ester (3), amide
      (4), and alcohol (5) analogues were inhibitors with IC50's ranging from 0.25 to
      1.0 mM. The hydroxamic acid (2) and amino (6) analogues did not inhibit the
      enzyme.

PMID- 16292826
TI  - Random isotopolog libraries for protein perturbation studies. 13C NMR studies on
      lumazine protein of Photobacterium leiognathi.
AB  - [graph: see text] Lumazine proteins of luminescent bacteria are paralogs of
      riboflavin synthase which are devoid of catalytic activity but bind the
      riboflavin synthase substrate, 6,7-dimethyl-8-ribityllumazine, with high affinity
      and are believed to serve as optical transponders for bioluminescence emission.
      Lumazine protein of Photobacterium leiognathi was expressed in a recombinant
      Escherichia coli host and was reconstituted with mixtures (random libraries) of
      13C-labeled isotopologs of 6,7-dimethyl-8-ribityllumazine or riboflavin that had
      been prepared by biotransformation of [U-(13)C6]-, [1-(13)C1]-, [2-(13)C1]-, and
      [3-(13)C1]glucose. 13C NMR analysis of the protein/ligand complexes afforded the
      assignments of the 13C NMR chemical shifts for all carbon atoms of the protein
      bound ligands by isotopolog abundance editing. The carbon atoms of the ribityl
      groups of both ligands studied were shifted up to 6 ppm upon binding to the
      protein. Chemical shift modulation of the side chain and chromophore carbon atoms
      due to protein/ligand interaction is discussed on the basis of the sequence
      similarity between lumazine protein and riboflavin synthase.

PMID- 16292828
TI  - Spherical shape complementarity as an overriding motif in the molecular
      recognition of noncharged organic guests by p-sulfonatocalix[4]arene:
      complexation of bicyclic azoalkanes.
AB  - [reaction: see text] The complexation of p-sulfonatocalix[4]arene (CX4) with 2,3
      diazabicyclo[2.2.1]hept-2-ene (1), 2,3-diazabicyclo[2.2.2]oct-2-ene (2), 2,3
      diazabicyclo[3.2.2]non-2-ene (3), 1-methyl-4-isopropyl-2,3-diazabicyclo[2.2.2]oct
      2-ene (4), and 1-phenyl-2,3-diazabicyclo[2.2.2]oct-2-ene (5) was studied in D2O
      at pD 7.4 by 1H NMR spectroscopy. The formation of deep inclusion complexes was
      indicated by large upfield 1H NMR shifts of the guest protons (up to 2.6 ppm),
      which were also used to assign, in combination with 2D ROESY spectra, a
      preferential inclusion of the isopropyl group of 4 and a dominant inclusion of
      the azo bicyclic residue for 5. The bicyclic azoalkanes 1-3 showed exceptionally
      high binding constants on the order of 1000 M(-1), 1-2 orders of magnitude larger
      than for previously investigated noncharged organic guest molecules. The strong
      binding was attributed to the spherical shape complementarity between the guest
      and the conical cavity offered by CX4. Interestingly, although the derivatives 4
      and 5 are more hydrophobic, they showed a 2-3 times weaker binding, which was
      again attributed to the deviation from spherical shape in these bridgehead
      substituted derivatives. The preferential inclusion of the hydrophilic but
      spherical bicyclic residue of 5 rather than the hydrophobic aromatic phenyl group
      provides a unique observation in aqueous host-guest chemistry and corroborates
      the pronounced spherical shape affinity of CX4.

PMID- 16292829
TI  - Dinuclear zinc(II) double-helicates of homochirally substituted
      bis(dipyrromethene)s.
AB  - [structure: see text] A series of bis(dipyrromethene)s substituted with aromatic
      amide and aliphatic ester homochiral auxiliaries have been prepared and complexed
      with zinc(II) ions to form double-helical dinuclear complexes. CD analysis of the
      crude complexes revealed that the helicates formed in a diastereoselective
      manner. The helicates have been resolved into their constituent M and P helices
      by HPLC, indicating that the helical sense of the complexes is stable to
      racemization.

PMID- 16292830
TI  - Aza-Baylis-Hillman reactions of N-tosylated aldimines with activated allenes and
      alkynes in the presence of various Lewis base promoters.
AB  - [reaction: see text] The attempted aza-Baylis-Hillman reactions of N-tosylated
      aldimines with ethyl 2,3-butadienoate, ethyl penta-2,3-dienoate, penta-3,4-dien-2
      one, methyl propiolate, and but-3-yn-2-one have been systematically investigated
      in the presence of various nitrogen or phosphine Lewis base promoters. We found
      that a series of nitrogen-containing heterocyclic compounds, as "abnormal" aza
      Baylis-Hillman reaction products, can be formed in the presence of an appropriate
      Lewis base promoter. The Lewis base and solvent effects in these reactions have
      been discussed along with the corresponding plausible mechanism.

PMID- 16292831
TI  - An efficient synthesis of coumestrol and coumestans by iodocyclization and Pd
      catalyzed intramolecular lactonization.
AB  - [reaction: see text] The iodocyclization of acetoxy-containing 2-(1
      alkynyl)anisoles and subsequent direct palladium-catalyzed
      carbonylation/lactonization provide an efficient route to naturally occurring
      coumestan and coumestrol, and their related analogues.

PMID- 16292832
TI  - Chemoenzymatic synthesis of HIV-1 V3 glycopeptides carrying two N-glycans and
      effects of glycosylation on the peptide domain.
AB  - [structure: see text] A highly efficient chemoenzymatic synthesis of HIV-1 V3
      domain glycopeptides carrying two N-linked core tri- and pentasaccharides was
      achieved. The synthesis consisted of two key steps: a solid-phase synthesis of
      the cyclic, 47-mer V3 domain peptide containing two GlcNAc residues and a novel
      endoglycosidase-catalyzed transglycosylation that simultaneously added two N
      glycan moieties to the peptide precursor from the oligosaccharide oxazoline donor
      substrates. The availability of the synthetic glycopeptides allowed the probing
      of the effects of glycosylation on the HIV-1 V3 domain. It was demonstrated that
      glycosylation influenced the global conformations of the V3 domain and provided
      protection of the V3 domain against protease digestion.

PMID- 16292833
TI  - Studies on taxadiene synthase: interception of the cyclization cascade at the
      isocembrene stage with GGPP analogues.
AB  - [reaction: see text] The cyclization of GGPP to taxadiene, catalyzed by taxadiene
      synthase, has been suggested to proceed through a series of monocyclic
      isocembrenyl- and bicyclic verticillyl-carbocationic intermediary stages. A set
      of GGPP analogues with abolished or perturbed pi-nucleophilicity at the delta10
      double bond (GGPP numbering) was synthesized and incubated with taxadiene
      synthase to intercept the cyclization cascade at the monocyclic stage. Each
      analogue was transformed by taxadiene synthase in vitro to hydrocarbon products
      in varying yields, and the structures of the major product in each reaction were
      solved by GCEIMS and one- and two-dimensional (1H and 13C) NMR and found to be 14
      membered monocyclic isocembrenyl diterpenes, indicating that the first C-C bond
      formation catalyzed by taxadiene synthase could be uncoupled from the other
      subsequent bond formation events by using suitably designed substrate analogues.
      The formation and isolation of these isocembrenyl diterpene products using
      taxadiene synthase supports proposals that the isocembrenyl cation is an
      intermediate in the cyclization of GGPP to taxadiene.

PMID- 16292834
TI  - Synthesis of HKI 0231B.
AB  - [reaction: see text] The total synthesis of HKI 0231B (1b) was completed in 12
      linear steps and 15.6% overall yield. An unusual anionic cyclization provided
      access to intermediate 61 and the embedded benz[cd]indol-3-(1H)-one ring system
      3. Directed ortho-lithiation in the presence of a ketone followed by formylation
      and finally acid-catalyzed methanolysis complete the synthesis. Studies directed
      toward the construction and reactivity of the lactam acetal functionality present
      in HKI 0231A (1a) are also reported.

PMID- 16292835
TI  - Efficient synthesis of furan-2-ylacetates, 7-(alkoxycarbonyl)benzofurans, and 7
      (alkoxycarbonyl)-2,3-dihydrobenzofurans based on cyclization reactions of free
      and masked dianions: a "cyclization/dehydrogenation" strategy.
AB  - [reaction: see text] A variety of furan-2-ylacetates have been prepared by
      dehydrogenation of monocyclic 2-alkylidenetetrahydrofurans, which are readily
      available by cyclizations of open-chained 1,3-dicarbonyl dianions with 1-bromo-2
      chloroethane. 5'H-[2,3']Bifuranyl-2'-ones are available based on sequential
      "cyclization/dehydrogenation" reactions of alpha-acetyl-gamma-butyrolactones. A
      variety of 7-(alkoxycarbonyl)benzofurans and 7-(alkoxycarbonyl)-2,3
      dihydrobenzofurans were prepared by a cyclization/dehydrogenation strategy. These
      reactions rely on cyclizations of 2-oxocycloalkane-1-carboxylate-derived 1,3
      dicarbonyl dianions ("free dianions") or 1,3-bis-silyl enol ethers ("masked
      dianions") with various 1,2-dielectrophiles.

PMID- 16292836
TI  - Regioselective synthesis of 1-aryl-3,4-substituted/annulated-5
      (methylthio)pyrazoles and 1-aryl-3-(methylthio)-4,5-substituted/annulated
      pyrazoles.
AB  - [reaction: see text] Highly efficient and regioselective synthesis of 1-aryl-3,4
      substituted/annulated-5-(methylthio)pyrazoles and 1-aryl-3-(methylthio)-4,5
      substituted/annulated pyrazoles has been reported via cyclocondensation of
      arylhydrazines with either alpha-oxoketene dithioacetals or beta-oxodithioesters.

PMID- 16292837
TI  - Conjugate additions of Me2CuLi to enantiopure gamma-hydroxy-delta-sulfinyl and
      sulfonyl pentenoates.
AB  - [reaction: see text] A systematic study of dimethyl cuprate conjugate additions
      to diastereoisomeric ethyl gamma-hydroxy (or tert-butyldimethylsilyloxy)-delta-p
      tolylsulfinyl-2-pentenoates and the analoguous sulfones showed mainly 3,4-anti
      diastereoselectivity when the reaction occurred in the presence of TMSCl. The pi
      facial diastereoselection is mainly governed by the gamma-hydroxy or silyloxy
      group, whereas the role of the sulfur functionality is to increase the reactivity
      of the pentenoate system, probably by assisting the transfer of the alkyl group
      from the cuprate. This was evidenced by the reactions on similar systems that
      lack the sulfur functions. The appropriate choice of NH4OH or HCl hydrolysis in
      the workup allowed direct access to the open chain products or the lactones.

PMID- 16292838
TI  - Development of the scope of a co-mediated O-->C rearrangement reaction.
AB  - [reaction: see text] In this paper we describe an Al-promoted, Co-mediated O-->C
      rearrangement reaction of cyclic enol ethers. This process delivers
      functionalized cyclohexanones with good to excellent levels of diastereocontrol,
      whereby the product stereochemistry is dependent on the E/Z-stereochemistry of
      the starting enol ether. The rearrangement process also permits access to highly
      substituted alpha-spirocyclic cyclohexanones as well as cyclopentanones. The
      latter rearrangement appears to proceed via an unusual 5-(enolendo)-exo-trig
      cyclization process.

PMID- 16292840
TI  - Static and dynamic stereochemistry of the conformational atropisomers of tetra(o
      tolyl)benzene.
AB  - [graph: see text] Whereas only one atropisomer of 1,2,4,5-tetra(o-tolyl)benzene
      was observed by X-ray diffraction in the solid, five conformational atropisomers
      were detected by low-temperature NMR in solution. Their structures were assigned
      by a combination of NOE experiments, solvent effect, and ab initio calculations.
      Variable temperature dynamic NMR and bidimensional EXSY experiments allowed the
      barrier for the interconversion of these atropisomers to be determined
      (deltaG(double dagger) = 15.3 kcal mol(-1)).

PMID- 16292839
TI  - Autoxidation of salvinorin A under basic conditions.
AB  - [reaction: see text] Treatment of salvinorin A (1a) with KOH in MeOH gave the
      enedione 3, for which the dienone structure 7 was recently proposed. Also
      isolated, after methylation, were the secotriesters 4a-c. A mechanism for this
      unusual series of autoxidations is proposed. Surprisingly, 4a showed weak
      affinity at the kappa-opioid receptor. Divinatorins A-C (2a-c) showed no affinity
      at opioid receptors. Attempted reduction of 3 to a novel salvinorin diol (9d) was
      unsuccessful, but careful deacetylation of salvinorin C (9a) provided a viable
      route to this compound. A general method for identifying salvinorin 8-epimers by
      TLC is also presented.

PMID- 16292841
TI  - Preorganizing linear (self-complementary) quadruple hydrogen-bonding arrays using
      intramolecular hydrogen bonding as the sole force.
AB  - [structures: see text] In this article we describe a rational approach for
      prefixing multiple cooperative binding sites in an ideal spatial arrangement on a
      structurally rigid backbone, constrained exclusively by intramolecular hydrogen
      bonding. The idea is exemplified by the ability of the self-assembling constructs
      1a-e and 2a,b to form hydrogen-bonded dimers, whose structural preorganization
      has been solely effected by intramolecular hydrogen bonding. The readily
      accessible amidinourea backbone has been used as a common platform for the
      construction of a variety of such self-assembling systems. ESI mass spectrometry
      and single-crystal X-ray diffraction studies have been particularly effective in
      investigating the self-assembling propensities of these systems. Remarkably, most
      the H-bonded dimers reported herein undergo an unusual mode of self-assembly,
      using intermolecular four-membered ring hydrogen-bonded interaction, affording
      extended supramolecular networks.

PMID- 16292842
TI  - Exchange interaction of 5,5'-(m- and p-phenylene)bis(10-phenyl-5,10
      dihydrophenazine) dications and related analogues.
AB  - [structures: see text] 5,5'-(m-Phenylene)bis[(10-aryl-5,10-dihydrophenazine)
      dications, 3a2+ and 3b2+, and their p-analogues 4a2+ and 4b2+, were prepared, and
      their exchange interaction was investigated. The EPR spectra of these dications
      at 123 K in a butyronitrile matrix showed the population of a triplet state. The
      temperature dependence of the EPR signal intensity (absolute value(delta m(s)) =
      2) showed that these dications had singlet ground states with deltaE(ST)/k(B) = 
      27 to -21 K for the m-isomer 3(2+) and with deltaE(ST)/k(B) = -10 to -8 K for the
      p-isomer 4(2+). Theoretical calculation of the exchange interaction J for these
      dications at the orthogonal torsion angle geometries was carried out for 3a2+ and
      4a2+ and for (m- and p-phenylene)bisphenothiazine dications 1(2+) and 2(2+) using
      the broken-symmetry approach for the singlet states. A good correlation was
      observed between the calculated J and a MO-energy term in the triplet state,
      deltaE(TMO) = absolute value(HOMO(alpha) - (HOMO - 1)(alpha)). The calculated J
      values were negative in the order of 10 K for the m-dications (J/k(B) = -14.7 K
      for 1(2+), -11.5 K for 3a(2+)), but much smaller negative values were found for
      the p-isomers (J/k(B) = -0.9 K for 2(2+), -0.8 K for 4a2+). The smaller absolute
      value(J) values for the p-dications are qualitatively consistent with the
      experimental deltaE(ST) (2J) values.

PMID- 16292843
TI  - Lewis acid mediated reactions of cyclopropyl aryl ketones with alpha-ketoesters:
      facile preparation of 5,6-dihydropyran-2-ones.
AB  - [reaction: see text] A new general method for the synthesis of 5,6-dihydropyran-2
      ones from cyclopropyl aryl ketones (monoactivated cyclopropanes) and alpha
      ketoesters in good to excellent yields has been developed. The process involves a
      cascade of reactions, including a nucleophilic ring-opening reaction of
      monoactivated cyclopropane by H2O, Lewis acid mediated transesterification, and
      an aldol type reaction.

PMID- 16292844
TI  - Improved methodologies for the preparation of highly substituted pyridines.
AB  - [reaction: see text] Two separate strategies have been developed for the
      preparation of highly substituted pyridines from 1,2,4-triazines via the inverse
      electron-demand Diels-Alder reaction: a microwave-promoted, solvent-free
      procedure and a tethered imine-enamine (TIE) approach. Both routes avoid the need
      for a discrete aromatization step and offer significant advantages over the
      classical methods, giving a wide variety of tri-, tetra-, and penta-substituted
      pyridines in high, optimized yields.

PMID- 16292846
TI  - A convenient and chemoselective one-pot oxidation/Wittig reaction for the C2
      homologation of carbohydrate-derived glycols.
AB  - [reaction: see text] A simple and convenient one-pot protocol for the
      chemoselective C2-homologation of carbohydrate-derived glycols is described. The
      method comprises the chemoselective oxidation of the glycol to the corresponding
      hydroxyaldehyde and the subsequent Wittig alkenylation. In addition, the method
      does not need selective protective group manipulation, and it is safe,
      economical, fast (5 to 6 h), and bench-friendly. Its general utility is
      discussed.

PMID- 16292845
TI  - Silver(I)-catalyzed novel cascade cyclization reactions: incorporation of allenes
      into the isochromenes.
AB  - [reaction: see text] The silver(I)-catalyzed reaction of alkynones with alcohols
      represents a general tool for the synthesis of 1-allenyl isochromenes. The
      reaction most probably proceeds via the formation of benzopyrylium cation, which
      subsequently undergoes nucleophilic attack of an alcohol to give the annulation
      products.

PMID- 16292847
TI  - Highly diastereoselective cyanation of methyl ketimines obtained from (R)
      glyceraldehyde.
AB  - [reaction: see text] Addition of trimethylsilyl cyanide to ketimines derived from
      (R)-2,2-dimethyl-1,3-dioxolan-4-yl methyl ketone to generate a quaternary
      stereocenter has been achieved with high yields and excellent
      diastereoselectivity. The stereoselectivity was found to be temperature and
      solvent dependent. The beta-hydroxy-alpha-amino nitrile of syn configuration was
      the major compound in kinetically controlled reactions, whereas the anti
      stereoisomer was obtained in excess in thermodynamically controlled reactions.
      Double stereodifferentiation under kinetic control conditions was successful, and
      the cyanation reaction occurred with complete syn diastereoselectivity using the
      matched pair. The versatility of the resulting amino nitrile as a synthetic
      intermediate was tested by performing the synthesis of orthogonally protected (R)
      (2-aminomethyl)alanine.

PMID- 16292848
TI  - Camphor ionic liquid: correlation between stereoselectivity and cation-anion
      interaction.
AB  - [structure: see text] As a halogen-free anion for an imidazolium room temperature
      ionic liquid, the use of a camphorsulfonate causes an increase in the number of
      free (naked) imidazolium cations, which produces an effective endo/exo
      stereoselective Diels-Alder reaction.

PMID- 16292849
TI  - A convergent ring-closing metathesis approach to carbohydrate-based macrolides
      with potential antibiotic activity.
AB  - [reaction: see text] An efficient convergent approach has been developed for the
      construction of novel, non-natural, carbohydrate-based macrolides. The key step
      in the synthesis is the formation of the macrocyclic ring via a ring-closing
      metathesis reaction. The obtained macrolide analogues have been screened for
      biological activity against gram-positive and gram-negative bacteria, including
      resistant strains, yeasts, and molds.

PMID- 16292850
TI  - Short and efficient synthesis of coronene derivatives via ruthenium-catalyzed
      benzannulation protocol.
AB  - [reaction: see text] TpRuPPh3(CH3CN)2PF6 (3 mol %) was very active in catalytic
      benzannulation of 1-phenyl-2-ethynylbenzenes in dichloroethane (60 degrees C, 36
      h) to afford phenanthrene in 95% yield. This method is applicable to the
      synthesis of various polycyclic aromatic hydrocarbons via two- and four-fold
      benzannulations, including various substituted coronene derivatives (53-86%
      yields) using this catalyst at a moderate loading (10 mol %).

PMID- 16292851
TI  - Synthesis of racemic cis-5-hydroxy-3-phthalimidoglutarimide. A metabolite of
      thalidomide isolated from human plasma.
AB  - [reaction: see text] A synthesis of the glutarimide-derived metabolite of
      thalidomide, 5'-hydroxythalidomide (2), is described. The synthesis employed the
      lactone derivative of N-benzyloxycarbonyl (CBZ)-protected 4-hydroxyglutamic acid
      12, which is prepared by a de novo route from diethyl acetamidomalonate. The
      reaction of 12 with 4-methoxybenzylamine gave the corresponding isoglutamine,
      which then provided the key CBZ-protected N-PMB-glutarimide 14 after dehydration.
      Deprotection of both the CBZ and PMB groups followed by phthalimidation and
      deacetylation of the 3-amino-5-acetoxyglutarimide 16 afforded 2.

PMID- 16292852
TI  - Stereospecific addition of H-P bond to alkenes: a simple method for the
      preparation of (R(P))-phenylphosphinates.
AB  - [reaction: see text] A variety of functionalized optically pure (R(P))
      alkylphenylphosphinates are readily prepared by stereospecific radical or base
      catalyzed additions of the easily available (R(P))-menthyl phenylphosphinate to
      alkenes.

PMID- 16292853
TI  - Enol tosylates as viable partners in Pd-catalyzed cross-coupling reactions.
AB  - [reaction: see text] Herein we demonstrate functionalized enol tosylates to be
      robust substrates that undergo Suzuki-Miyaura, Sonogashira, and Stille cross
      coupling reactions to provide stereodefined trisubstituted unsaturated esters.

PMID- 16292854
TI  - An efficient synthesis of the constrained peptidomimetic 2-oxo-3-(N-9
      fluorenyloxycarbonylamino)-1-azabicyclo[4.3.0]nonane-9-carboxylic acid from
      pyroglutamic acid.
AB  - [reaction: see text] Azabicyclo[X.Y.0]alkane amino acids are rigid dipeptide
      mimetics that are useful tools for structure-activity studies in peptide-based
      drug discovery. Herein, we report an efficient synthesis of three diastereomers
      of 9-tert-butoxycarbonyl-2-oxo-3-(N-tert-butoxycarbonylamino)-1
      azabicyclo[4.3.0]nonane (3S,6S,9S, 3S,6R,9R, and 3S,6R,9S). Methyl N-Boc
      pyroglutamate is cleaved with vinylmagnesium bromide to produce an acyclic gamma
      vinyl ketone. Michael addition of N-diphenylmethyleneglycine tert-butyl ester
      produces the N-Boc-delta-oxo-alpha,omega-diaminoazelate intermediate, which, on
      hydrogenloysis, gives the fused ring system. Acidolytic deprotection followed by
      Fmoc-protection provided building blocks suitable for solid-phase synthesis.

PMID- 16292855
TI  - Facile rearrangement of O-silylated oximes on reduction with boron
      trifluoride/borane.
AB  - [reaction: see text] Aromatic O-triisopropylsilyl ketoximes were efficiently
      rearranged to cyclic and acyclic aniline derivatives on reduction with BF3
      ethearate/borane. The bulk of the substituents on the silicon atom, the size of
      the aliphatic ring, and the presence of alkoxy substituents on the aryl group all
      play an important role in the aniline.

PMID- 16292856
TI  - A soluble base for the copper-catalyzed imidazole N-arylations with aryl halides.
AB  - [reaction: see text] CuI-catalyzed N-arylation of imidazoles with aryl bromides
      has been achieved in a near-homogeneous system that utilizes tetraethylammonium
      carbonate as base, 8-hydroxyquinoline as ligand, and H2O as cosolvent.
      Preliminary results with aryl chlorides are also reported.

PMID- 16292858
TI  - Practical synthesis of Shi's diester fructose derivative for catalytic asymmetric
      epoxidation of alkenes.
AB  - [reaction: see text] A practical synthesis of Shi's diester 3 for catalytic
      asymmetric epoxidations has been developed. The catalyst has been prepared in
      multigram quantities from D-fructose in four steps with a 66% overall yield.
      Efficiency, cost, and selectivity aspects of the reagents involved for its
      preparation have been taken care of during its preparation. The workup procedures
      have been simplified to the bare minimum, rendering a very practical preparation
      method. The well-known high efficiency of this catalyst 3 in the epoxidation of
      alpha,beta-unsaturated carbonyl compounds has also proved to be high in
      unfunctionalized alkenes.

PMID- 16292857
TI  - A short synthesis of (+)-cyclophellitol.
AB  - [reaction: see text] A new synthesis of (+)-cyclophellitol, a potent beta
      glucosidase inhibitor, has been completed in nine steps from D-xylose. The key
      transformations involve a zinc-mediated fragmentation of benzyl-protected methyl
      5-deoxy-5-iodo-xylofuranoside followed by a highly diastereoselective indium
      mediated coupling with ethyl 4-bromocrotonate. Subsequent ring-closing olefin
      metathesis, ester reduction, olefin epoxidation, and deprotection then afford the
      natural product. This constitutes the shortest synthesis of (+)-cyclophellitol
      reported to date.

PMID- 16292860
TI  - Construction of a 2,6-difunctionalized 2-methyl-2H-1-benzopyran library by using
      a solid-phase synthesis protocol.
AB  - [reaction: see text] A library containing 1200 analogues of 2,6-difunctionalized
      2-methyl-2H-1-benzopyran was constructed by using a solid-phase synthesis
      protocol. Polymer-bound 6-amido-, 6-sulfonamido-, and 6-uredo-functionalized 2
      hydroxymethyl-2-methylbenzopyrans 10 were prepared as part of a first-generation
      diversification step by employing reactions of respective acid halides, sulfonyl
      chlorides, and isocyanates with the amine precursor 7. Transformations of the
      resin-bound intermediates 10 by reactions with alkyl and acid halides were then
      used to produce a diverse series of 2,6-difunctionalized 2-methyl-2H-1-benzopyran
      analogues 12 and 14.

PMID- 16292859
TI  - Rhombimines-cyclic tetraimines of trans-1,2-diaminocyclohexane shaped by the
      diaryl ether structural motif.
AB  - [reaction: see text] Rhombimines, chiral macrocyclic tetraimines, are
      preferentially formed because of the structural bias in the reaction of aromatic
      ether-linked dialdehydes with enantiomerically pure trans-1,2-diaminocyclohexane.

PMID- 16292861
TI  - Rational tuning chelate size of bis-oxazoline ligands to improve
      enantioselectivity in the asymmetric aziridination of chalcones.
AB  - [reaction: see text] Chalcones were asymmetrically aziridinated with [N-(p
      toluenesulfonyl)imino]phenyliodinane (PhI=NTs) as a nitrene source under
      catalysis of CuOTf and a series of cyclohexane-linked bis-oxazolines (cHBOXes),
      which are chelate size rationally tuned bis-oxazolines. The results indicate that
      highly enantioselective aziridination of chalcones with up to >99% ee have been
      achieved under catalysis of (S,S)-1,2-bis[(S)-(4-phenyl)oxazolin-2
      yl]cyclohexane, which is the most-matched stereoisomer among cyclohexane-linked
      bis-oxazolines. It was also found that the enantioselectivity is not substituent
      dependent with respect to chalcones in the present case, unlike with 1,8
      anthracene-linked bis-oxazolines (AnBOXes).

PMID- 16292862
TI  - Reductive one-carbon homologation of aldehydes and ketones.
AB  - [reaction: see text] A rhodium-catalyzed methylenation-hydrogenation cascade
      process allows the homologation of carbonyl compounds to lead to the
      corresponding alkanes in high yields.

PMID- 16292863
TI  - Synthesis of ovalicin starting from D-mannose.
AB  - [reaction: see text] A new synthesis of epoxyketone 22 is described that is a key
      intermediate in Barton's synthesis of ovalicin (2), a powerful anti-angiogenetic
      inhibitor. The key process for the construction of 22 was ring-closing metathesis
      of olefins 11 and 12 obtained from 2,3:5,6-di-O-isopropylidene-alpha-D
      mannofuranose (4) and regioselective desilylation of tri-TES ether 19.
      Furthermore, an alternative stereoselective route from 22 into 2 has also been
      developed, and the overall yield of 2 from 4 was 10.0%.

PMID- 16292864
TI  - Sequential intermediates in the base-catalyzed conversion of bis(pi-conjugated
      propargyl) sulfones to 1,3-dihydrobenzo- and naphtho[c]thiophene-2,2-dioxides.
AB  - [reaction: see text] In a recent article, we reported on the base-catalyzed
      rearrangements of dipropargyl selenides, -sulfides, -sulfoxides, and -sulfones
      that eventually lead to polycyclic aromatic products. In the present work, we
      report on the first isolation and characterization of the thiophene dioxide
      intermediates 5b,c from a mild tandem isomerization/cyclization/aromatization of
      bis(pi-conjugated propargyl) sulfones. Monoallene 2b,c and diallene 3b
      intermediates were also identified by NMR. A kinetic study of the rearrangement
      of 1a-c revealed that the unusual facile tandem process is highly dependent on
      the nature of gamma-substitution.

PMID- 16292865
TI  - A convenient method for synthesizing modified 4-nitrophenols.
AB  - [reaction: see text] Beta-nitroenamine having a formyl group behaves as the
      synthetic equivalent of unstable nitromalonaldehyde upon treatment with ketones
      under basic conditions and leads to 2,6-disubstituted 4-nitrophenols. The present
      method is safer than the conventional one using sodium nitromalonaldehyde and
      enables the preparation of hitherto unknown nitrophenols.

PMID- 16292866
TI  - Regioselective one-step synthesis of 4-fluoroalkylated isoquinolines via
      carbopalladation reaction of fluorine-containing alkynes.
AB  - [reaction: see text] The palladium-catalyzed annulation reaction of
      fluoroalkylated alkynes with various 2-iodobenzylidenamines was investigated. In
      the presence of a catalytic amount of Pd(PPh3)4, the reaction took place smoothly
      to give the corresponding 4-fluoroalkylated isoquinoline in high yield as a
      single isomer. No other regioisomer was detected.

PMID- 16292867
TI  - Ferrocenylphosphines as new catalysts for Baylis-Hillman reactions.
AB  - [reaction: see text] Readily available ferrocenyldialkylphosphines are effective
      air-stable catalysts for Baylis-Hillman reaction between aldehydes and acrylates,
      affording the corresponding adducts in high yields and short reaction times. A
      set of readily accessible planar chiral ferrocenyldialkylphosphines have been
      tested in asymmetric Baylis-Hillman reactions. The best enantioselectivities were
      obtained using Mandyphos as chiral catalyst (up to 65% ee).

PMID- 16292868
TI  - Facile preparation of a new BINAP-based building block, 5,5'-diiodoBINAP, and its
      synthetic application.
AB  - [reaction: see text] Bis(pyridine)iodonium tetrafluoroborate was successfully
      used for regioselective iodination of BINAP dioxide to give 5,5'-diiodoBINAP
      dioxide in an excellent yield of 92%, with no observed formation of 4,4'
      diiodoBINAP dioxide. A Sonogashira cross-coupling reaction with 5,5'-diiodoBINAP
      dioxide gave the desired bis(trimethylsilylethynyl) product in 86% yield. The
      resulting 5,5'-disubstituted BINAP dioxides were reduced to the corresponding
      phosphines, which were used as chiral ligands for rhodium-catalyzed asymmetric
      1,4-addition of phenylboronic acid to 2-cyclohexenone to give 3
      phenylcyclohexanone in excellent yield with high enantioselectivity.

PMID- 16292869
TI  - Stereoselective total synthesis of cis- and trans-3-hydroxypipecolic acid.
AB  - [reaction: see text] 3-Hydroxypipecolic acid, a nonproteinogenic cyclic alpha
      amino acid, is a common structural moiety found in a large number of natural and
      synthetic compounds of medicinal significance. Utilizing D-serine as a chiral
      template, the present research describes efficient and straightforward routes to
      cis- and trans-3-hydroxypipecolic acids in enantiopure form. The key steps in the
      syntheses involve chelation-controlled addition of a homoallyl Grignard reagent
      to a protected serinal derivative toward stereoselective formation of the
      corresponding syn-amino alcohol adduct 3. On the other hand, zinc borohydride
      mediated chelation-controlled reduction of a serine-derived alpha-aminoketone
      precursor leads to the formation of the corresponding anti-amino alcohol adduct 4
      with high stereoselectivity. Following an efficient sequence of reactions, the
      above amino alcohol derivatives were subsequently transformed to the
      corresponding cis- and trans- title compounds, respectively.

PMID- 16292870
TI  - Mild and practical method for the alpha-arylation of nitriles with heteroaryl
      halides.
AB  - [reaction: see text] A mild and transition-metal-free method for the alpha
      arylation of aliphatic nitriles with activated heteroaryl halides was developed
      using NaHMDS or KHMDS as base at ambient temperature. The key to the success of
      this method is generation of the nitrile anion in the presence of the heteroaryl
      halide. The method is applicable to both primary and secondary carbonitriles and
      a wide range of heteroaryl halides. Selective monoarylation was observed with
      primary carbonitriles. The operational simplicity and the mild reaction
      conditions add to the value of this method as a practical alternative to the
      preparation of alpha-heteroaryl carbonitriles.

PMID- 16292871
TI  - Lewis base catalyzed enantioselective aldol addition of acetaldehyde-derived
      silyl enol ether to aldehydes.
AB  - [reaction: see text] Chiral phosphoramide catalyzed-enantioselective aldol
      addition of an acetaldehyde-derived trialkylsilyl enol ether to aromatic
      aldehydes provides protected aldol products in good yields with good to excellent
      enantioselectivities. Preliminary studies show that the aldolization intermediate
      (a chlorohydrin adduct) can be trapped with tert-butyl isocyanide to form an
      alpha-hydroxy lactone with good selectivity in a single-pot operation.

PMID- 16292872
TI  - Single-step syntheses of 2-amino-7-chlorothiazolo[5,4-d]pyrimidines:
      intermediates for bivalent thiazolopyrimidines.
AB  - [reaction: see text] A single-step process for the preparation of 2-amino-7
      chlorothiazolo[5,4-d]pyrimidines, 2, was achieved by the reaction of the
      commercially available 4,6-dichloro-5-aminopyrimidine 1 with isothiocyanates.
      This mild reaction accommodates a variety of functionalized isothiocyanates and
      proceeds in good to excellent yields. The utility of such intermediates is
      exemplified by subsequent reaction with alkyl or arylamine nucleophiles to afford
      novel, differentially functionalized 2,7-diaminothiazolo[5,4-d]pyrimidines, 3.

PMID- 16292873
TI  - A high-yield, one-step synthesis of o-phenylene ethynylene cyclic trimer via
      precipitation-driven alkyne metathesis.
AB  - [reaction: see text] A shape-persistent, conjugated o-phenylene ethynylene cyclic
      trimer was prepared in one step from tetrasubstituted benzene monomer 4 in 86%
      isolated yield through precipitation-driven alkyne metathesis. The template-free,
      selective generation of the molecular triangle 5 is a thermodynamically favored
      process and under equilibrium control. A novel tetrameric macrocycle 7 was
      generated via scrambling metathesis between tricycle 5 and hexacycle 6 using this
      dynamic covalent chemistry.

PMID- 16292874
TI  - Highly stereoselective synthesis of trisubstituted vinylcyclopropane derivatives
      via arsonium ylides.
AB  - [reaction: see text] Alkylidene or arylidene malonates reacted with arsonium
      allylides to give trans-disubstituted cyclopropane-1,1-dicarboxylates with high
      stereoselectivity in high yields. The mechanism of the cyclopropanation reactions
      has also been investigated.

PMID- 16292875
TI  - Synthesis of 3-amino-1,2,4-benzothiadi- azine 1,1-dioxides via a tandem aza
      Wittig/heterocumulene annulation.
AB  - [reaction: see text] Reaction of o-azidobenzenesulfonamides with polymer
      supported triphenylphosphine affords the corresponding iminophosphoranes.
      Subsequent reaction with isocyanates gives 3-amino-1,2,4-benzothiadiazine 1,1
      dioxides in high yields and purities. The reaction has been successfully applied
      to the synthesis of derivatives with various substituents at the 2- and 3
      positions and in the benzenoid ring.

PMID- 16292876
TI  - IBX-mediated alpha-hydroxylation of alpha-alkynyl carbonyl systems. A convenient
      method for the synthesis of tertiary alcohols.
AB  - [reaction: see text] IBX (o-iodoxybenzoic acid) is an excellent reagent for the
      alpha-hydroxylation of alpha-alkynyl carbonyl compounds without giving
      dehydrogenation products. The convenient procedure proves to be useful for the
      construction of a variety of tertiary alcohols (55-91%) under mildly acidic
      conditions.

PMID- 16292877
TI  - Nanotechnology in cancer detection and treatment.

PMID- 16292879
TI  - Fluorescent nanoparticle probes for cancer imaging.
AB  - Optical imaging technique has strong potential for sensitive cancer diagnosis,
      particularly at the early stage of cancer development. This is a sensitive, non
      invasive, non-ionizing (clinically safe) and relatively inexpensive technique.
      Cancer imaging with optical technique however greatly relies upon the use of
      sensitive and stable optical probes. Unlike the traditional organic fluorescent
      probes, fluorescent nanoparticle probes such as dye-doped nanoparticles and
      quantum dots (Qdots) are bright and photostable. Fluorescent nanoparticle probes
      are shown to be very effective for sensitive cancer imaging with greater success
      in the cellular level. However, cancer imaging in an in vivo setup has been
      recently realized. There are several challenges in developing fluorescent
      nanoparticle probes for in vivo cancer imaging applications. In this review, we
      will discuss various aspects of nanoparticle design, synthesis, surface
      functionalization for bioconjugation and cancer cell targeting. A brief overview
      of in vivo cancer imaging with Qdots will also be presented.

PMID- 16292878
TI  - Mitochondrial correlation microscopy and nanolaser spectroscopy - new tools for
      biophotonic detection of cancer in single cells.
AB  - Currently, pathologists rely on labor-intensive microscopic examination of tumor
      cells using century-old staining methods that can give false readings. Emerging
      BioMicroNano-technologies have the potential to provide accurate, realtime, high
      throughput screening of tumor cells without the need for time-consuming sample
      preparation. These rapid, nano-optical techniques may play an important role in
      advancing early detection, diagnosis, and treatment of disease. In this report,
      we show that laser scanning confocal microscopy can be used to identify a
      previously unknown property of certain cancer cells that distinguishes them, with
      single-cell resolution, from closely related normal cells. This property is the
      correlation of light scattering and the spatial organization of mitochondria. In
      normal liver cells, mitochondria are highly organized within the cytoplasm and
      highly scattering, yielding a highly correlated signal. In cancer cells,
      mitochondria are more chaotically organized and poorly scattering. These
      differences correlate with important bioenergetic disturbances that are hallmarks
      of many types of cancer. In addition, we review recent work that exploits the new
      technology of nanolaser spectroscopy using the biocavity laser to characterize
      the unique spectral signatures of normal and transformed cells. These optical
      methods represent powerful new tools that hold promise for detecting cancer at an
      early stage and may help to limit delays in diagnosis and treatment.

PMID- 16292880
TI  - In vivo biodistribution of dendrimers and dendrimer nanocomposites --
      implications for cancer imaging and therapy.
AB  - Our results indicate that the surface chemistry, composition, and 3-D structure
      of nanoparticles are critical in determining their in vivo biodistribution, and
      therefore the efficacy of nanodevice imaging and therapies. We demonstrate that
      gold/dendrimer nanocomposites in vivo, present biodistribution characteristics
      different from PAMAM dendrimers in a B16 mouse tumor model system. We review
      important chemical and biologic uses of these nanodevices and discuss the
      potential of nanocomposite devices to greatly improve cancer imaging and therapy,
      in particular radiation therapy. We also discuss major issues confronting the use
      of nanoparticles in the near future, with consideration of toxicity analysis and
      whether biodegradable devices are needed or even desirable.

PMID- 16292881
TI  - Long-circulating polymeric nanovectors for tumor-selective gene delivery.
AB  - Significant advances in the understanding of the genetic abnormalities that lead
      to the development, progression, and metastasis of neoplastic diseases has raised
      the promise of gene therapy as an approach to medical intervention. Most of the
      clinical protocols that have been approved in the United States for gene therapy
      have used the viral vectors because of the high efficiency of gene transfer.
      Conventional means of gene delivery using viral vectors, however, has undesirable
      side effects such as insertion of mutational viral gene into the host genome and
      development of replication competent viruses. Among non-viral gene delivery
      methods, polymeric nanoparticles are increasingly becoming popular as vectors of
      choice. The major limitation of these nanoparticles is poor transfection
      efficiency at the target site after systemic administration due to uptake by the
      cells of reticuloendothelial system (RES). In order to reduce the uptake by the
      cells of the RES and improve blood circulation time, these nanoparticles are
      coated with hydrophilic polymers such as poly(ethylene glycol) (PEG). This
      article reviews the use of such hydrophilic polymers employed for improving the
      circulation time of the nanocarriers. The mechanism of polymer coating and
      factors affecting the circulation time of these nanocarriers will be discussed.
      In addition to the long circulating property, modifications to improve the target
      specificity of the particles and the limitations of steric protection will be
      analyzed.

PMID- 16292882
TI  - The molecular analysis of breast cancer utilizing targeted nanoparticle based
      ultrasound contrast agents.
AB  - This study was structured to challenge the hypothesis that nano-sized
      particulates could be molecularly targeted and bound to the prognostic and
      predictive HER-2/neu cell membrane receptor to elicit detectable changes in
      ultrasound response from human breast cancer cells. SKBR-3 human breast cancer
      cells were enlisted to test the efficacy of the particle conjugation strategy
      used in this study and ultimately, to provide conclusive remarks regarding the
      validity of the stated hypothesis. A characterization-mode ultrasound (CMUS)
      system was used to apply a continuum mechanics based, two-step inversion
      algorithm to reconstruct the mechanical material properties of four cell/agarose
      test conditions upon three independent test samples. The four test conditions
      include: Herceptin conjugated iron oxide nanoparticles bound to cells (HER-con),
      Herceptin bound to cells (HER), iso-type matched antibody conjugated iron oxide
      nanoparticles bound to cells (ISO-con), and Cold Flow Buffer mixed with agarose
      (CFB). The statistical analysis of these ultrasound results supported the ability
      to differentiate between HER-2/neu positive SKBR-3 cells that have been
      successfully tagged with Herceptin(R) conjugated iron oxide particles to those
      that have not demonstrated particle binding. These findings serve as promising
      proof-of-concept data for the development of a quantitative histopathologic
      evaluation tool directed towards both in situ and in vivo applications. The
      ultimate goal of this research is to exploit the molecular expression of the HER
      2/neu protein to offer rapid, quantitative ultrasound information concerning the
      malignancy rating of human breast tissue employing tumor targeting nanoparticle
      based ultrasound contrast agents. When fully developed, this could potentially
      help 32,000-63,000 women efficiently find their proper treatment strategy to
      fight and win their battle against breast cancer.

PMID- 16292883
TI  - Targeted gene delivery to cancer cells with nanometric DNA particles enveloped
      with folic acid using a polymerisable anchor.
AB  - Progress in the design of gene delivery system is vital for cancer gene therapy
      since many physiological and intracellular barriers remain. We have developed a
      technology for condensing genes into nanometric delivery systems. In this paper,
      we present a novel strategy for decorating 30 nm DNA particles with folic acid
      for cancer cell recognition. Physicochemical and biological experiments show that
      these DNA complexes selectively bind to cells expressing the corresponding folic
      acid receptor.

PMID- 16292884
TI  - Role of nanobiotechnology in developing personalized medicine for cancer.
AB  - Personalized medicine simply means the prescription of specific therapeutics best
      suited for an individual. Personalization of cancer therapies is based on a
      better understanding of the disease at the molecular level. Nanotechnology will
      play an important role in this area. Nanobiotechnology is being used to refine
      discovery of biomarkers, molecular diagnostics, drug discovery and drug delivery,
      which are important basic components of personalized medicine and are applicable
      to management of cancer as well. Examples are given of the application of quantum
      dots, gold nanoparticles, and molecular imaging in diagnostics and combination
      with therapeutics -- another important feature of personalized medicine.
      Personalized medicine is beginning to be recognized and is expected to become a
      part of medical practice within the next decade. Personalized management of
      cancer, facilitated by nanobiotechnology, is expected to enable early detection
      of cancer, more effective and less toxic treatment increasing the chances of
      cure.

PMID- 16292885
TI  - Nanoparticles and cell longevity.
AB  - The field of engineering has made substantial strides in nanotechnology, in the
      realm of materials science and construction of nanoscale devices. Nanomedicine
      encompasses application of cutting edge engineered nanostructures to biological
      systems and development of novel strategies for disease intervention. In the
      current review, we discuss the pharmacological application of nanoparticles as
      free radical scavengers and the capacity of nanoparticles to promote cell and
      organismal longevity.

PMID- 16292886
TI  - Helical tomotherapy as a means of delivering scalp-sparing whole brain radiation
      therapy.

PMID- 16292887
TI  - Lasers in cancer detection and diagnosis research: enabling characteristics with
      illustrative examples.
AB  - The salient properties of laser light and the way light interacts with biological
      tissues and molecular constituents of tissues offer possibilities for detection
      and diagnosis of cancer. In particular, the wavelength selectivity of tunable
      lasers, narrow bandwidth around the selected wavelength, and spectral brightness
      enable probing of key molecular constituents of tissues, and endow laser-based
      techniques with much desired diagnostic potential. This article presents an
      overview of some recent developments in optical imaging and optical biopsy of
      different types of cancers, and illustrates the diagnostic role of the color of
      light.

PMID- 16292888
TI  - Intensity-modulated radiation therapy (IMRT) for newly diagnosed and recurrent
      intracranial meningiomas: preliminary results.
AB  - The purpose of this study was to evaluate tumor control, complications, and
      outcome from intensity-modulated radiation therapy (IMRT) for intracranial
      meningiomas. Between July 1997 and November 2003, patients with intracranial
      meningiomas were treated at our institution with the NOMOS Peacock system
      utilizing the Multileaf Intensity Modulating Collimator (MIMiC). Thirty-five
      patients with 37 lesions (35 benign and two atypical histology) were identified
      with a minimum of six months of radiologic follow-up for this retrospective
      review. The median age of the patients was 65 years with a median KPS of 90 prior
      to treatment with IMRT. The median MRI/CT follow-up for the 37 treated lesions
      was 19.1 months (range 6.4-62.4 months). Twenty meningiomas (54%) were previously
      treated with surgery/radiosurgery prior to IMRT, and 17 meningiomas (46%) were
      treated with IMRT primarily after diagnosis was established by MRI/CT. The median
      time from previous surgery to treatment with IMRT was 18.1 months. The median
      tumor dose was 50.4 Gy prescribed to the 87% isodose line providing a median
      target coverage of 95%. Local control was at 97% three years after treatment with
      IMRT. Only three patients exhibited local failure after treatment. Although local
      control was slightly better in the upfront-IMRT lesions as compared to the
      lesions treated with prior surgery/radiosurgery (100% vs 95%), this difference
      was not statistically significant. On univariate analysis, the IMRT prescription
      dose and maximum dose were found to be predictors for local control (p=0.05). On
      multivariate analysis, these factors did not remain significant for influencing
      local control. No long-term complications from IMRT were documented among the 35
      patients. In conclusion, intensity-modulated radiation therapy is a safe and
      effective treatment for some intracranial meningiomas. A greater number of
      patients with longer follow-up after treatment may be needed to determine
      treatment variables predicting for long-term tumor control.

PMID- 16292889
TI  - Evaluation of integral dose in cranio-spinal axis (CSA) irradiation with
      conventional and helical delivery.
AB  - In cranio-spinal axis (CSA) irradiation, patients are usually treated in the
      prone position with junctions between cranial and spinal fields. Collimator angle
      and pedestal rotations are introduced to obtain coplanar alignment of the matched
      junction. Furthermore, daily moving junctions are commonly used to feather out
      the junctional dose as additional safeguards to avoid radiation myelopathy.
      Helical tomotherapy integrates linear accelerator and CT technology capable of
      delivering CSA treatment without geometric matches or feathering of junctions.
      The patient is treated with helical beams in the supine position. Since CSA is
      used mainly in the pediatric population, the potential increase in integral dose
      to structures or the whole body from linac- or tomotherapy-based IMRT raises
      concerns of increased rates of secondary malignancies. In this study, we will
      present an integral dose comparison between conventional CSA (3D) and helical
      delivery to the CSA (TOMO) utilizing the Tomotherapy Hi-ART system for three
      pediatric patients. Integral dose was calculated for organ at risk (OAR), two
      targets (PTV-BRAIN and PTV-SPINE), entire planning CT data set and to the healthy
      tissue (entire CT-DATA SET minus the PTV). Overall integral dose was 8% higher in
      the TOMO plans for Patients #1 and #3, but 2% lower in Patient #2. DVH analysis
      shows that TOMO plans give lower doses to larger volumes and higher doses to
      smaller volumes of tissue in all three cases. The advantages of the TOMO plans
      are minimization of matched junctions and better sparing of most OARs. With
      increased computational and memory power in the tomotherapy planning station, the
      excess integral dose to the healthy tissue can be re-distributed within the
      patient and in turn the total integral dose can be same or lower than in
      conventional delivery. The impact of a small increase in overall integral dose
      and the associated risks of secondary malignancies are unknown. Long-term follow
      up is needed to answer this question.

PMID- 16292890
TI  - The use of tyrosine kinase inhibitors in modifying the response of tumor
      microvasculature to radiotherapy.
AB  - The response of the tumor microvasculature to ionizing radiation can be modified
      to improve tumor control in preclinical mouse models of cancer. Recent studies
      have shown that a variety of cancer drugs can improve the response of cancers to
      radiotherapy. Protein tyrosine kinase inhibitors (TKIs) have been shown to
      enhance radiation-induced destruction of tumor blood vessels. Among these
      compounds are inhibitors of a broad spectrum of receptor tyrosine kinases (RTKs).
      Inhibition of RTKs attenuates downstream signaling from various angiogenic growth
      factors, including vascular endothelial growth factor (VEGF), platelet-derived
      growth factor (PDGF), and fibroblast growth factor (FGF). RTK inhibitors with
      various specificities against the receptors for VEGF, PDGF, and FGF manifest
      significant antiangiogenic activities as well. We have shown using tumor vascular
      window model and tumor growth delay assays that these compounds can enhance tumor
      radiation response by attacking tumor microvasculature. Furthermore, we have
      shown that radiation and RTK inhibitors exert their antiangiogenic effect through
      inhibition of the PI3K/Akt signaling pathway, which results in induction of
      apoptosis. Our studies have provided a basis for future clinical investigations
      of combining radiotherapy and RTK inhibitors.

PMID- 16292891
TI  - Cancer cells ablation with irreversible electroporation.
AB  - In this study we perform in vitro irreversible electroporation (IRE) experiments
      with human hepatocarcinoma cells (HepG2) to investigate IRE as a new technique
      for undesirable tissue ablation. Irreversible electroporation (IRE) is the
      irreversible permeabilization of the cell membrane through the application of
      microsecond through millisecond electrical pulses. Until now IRE was studied only
      as an undesirable condition during the use of reversible electroporation in gene
      therapy and electrochemotherapy. There was a possibility that the IRE ablation
      domain is mostly superimposed on the electrical pulses induced Joule heating
      thermal ablation domain. This study demonstrates that there is a real and
      substantial domain of electrical parameters for IRE ablation of cancer that is
      distinct from the thermal domain and which results in complete cancer cell
      ablation. Experiments show that the application of 1500 V/cm in three sets of ten
      pulses of 300 microseconds each can produce complete cancer cell ablation. We
      also find that the use of multiple pulses appears to be more effective for cancer
      cell ablation than the application of the same energy in one single pulse.

PMID- 16292892
TI  - The comet assay to determine the mode of cell death for the ultrasonic delivery
      of doxorubicin to human leukemia (HL-60 Cells) from Pluronic P105 micelles.
AB  - This notes examines the mode of cell death of HL-60 cells exposed to 70 kHz and
      1.3 W/cm(2) ultrasound in the presence of 1% Pluronic P105 and 1.67 microg/ml
      doxorubicin (Dox). The cells were ultrasonicated for 30, 60, and 120 minutes.
      They were then lysed, electrophorised, stained using propidium iodide, and their
      DNA profile captured using a fluorescent microscope. The gradual DNA damage
      observed and the comet tails captured after one and two hours of insonation
      suggest that the mode of cell killing is apoptosis.

PMID- 16292893
TI  - Multipole-based integral estimates for the rigorous description of distance
      dependence in two-electron integrals.
AB  - We derive multipole-based integral estimates (MBIE) as rigorous and tight upper
      bounds to four-center two-electron integrals in order to account for the 1/R
      distance decay between the charge distributions, which is missing in the Schwarz
      screening commonly used in ab initio methods. Our screening criteria are valid
      for all angular momenta and can be formulated for any order of multipoles. We
      have found the expansion limited to dipoles to be sufficiently tight for
      estimating the integrals in Hartree-Fock and density-functional theories, while
      the screening effort is negligible. For, e.g., a DNA fragment with 1052 atoms and
      10,674 basis functions (6-31G*) the exchange part is faster by a factor of 2.1 as
      compared to the Schwarz screening both within our linear exchange scheme, whereas
      a smaller factor of 1.3 is gained for the Coulomb part within the continuous fast
      multipole method. Most importantly, our new MBIE screening is perfectly suited to
      exploit the strong distance decay of electron-correlation effects of at least
      1/R4 in atomic-orbital-based formulations of correlation methods.

PMID- 16292894
TI  - Rigorous integral screening for electron correlation methods.
AB  - We derive rigorous multipole-based integral estimates (MBIE) in order to account
      for the distance dependence occurring in atomic-orbital (AO) formulations of
      electron correlation theory, where our focus is on AO-MP2 theory within a Laplace
      scheme. We find for the exact transformed integral products an extremely early
      onset of a linear-scaling behavior and a very small number of significant
      products. To preselect the significant integral products we adapt our MBIE method
      as rigorous upper bound. In this way it is possible to exploit the favorable
      scaling behavior observed and to reduce the scaling of estimated products
      asymptotically to linear, without sacrificing accuracy or reliability. By
      separating Coulomb- and exchange-type contractions only half-transformed
      integrals need to be computed. Furthermore, our scheme of rigorously preselecting
      transformed integral products via MBIE seems to offer particularly interesting
      perspectives for a direct formation of half- or fully transformed integrals by
      using multipole expansions and auxiliary basis sets.

PMID- 16292895
TI  - Transition state theory: variational formulation, dynamical corrections, and
      error estimates.
AB  - Transition state theory (TST) is revisited, as well as evolutions upon TST such
      as variational TST in which the TST dividing surface is optimized so as to
      minimize the rate of recrossing through this surface and methods which aim at
      computing dynamical corrections to the TST transition rate constant. The theory
      is discussed from an original viewpoint. It is shown how to compute exactly the
      mean frequency of transition between two predefined sets which either partition
      phase space (as in TST) or are taken to be well-separated metastable sets
      corresponding to long-lived conformation states (as necessary to obtain the
      actual transition rate constants between these states). Exact and approximate
      criterions for the optimal TST dividing surface with minimum recrossing rate are
      derived. Some issues about the definition and meaning of the free energy in the
      context of TST are also discussed. Finally precise error estimates for the
      numerical procedure to evaluate the transmission coefficient kappaS of the TST
      dividing surface are given, and it is shown that the relative error on kappaS
      scales as 1/square root(kappaS) when kappaS is small. This implies that dynamical
      corrections to the TST rate constant can be computed efficiently if and only if
      the TST dividing surface has a transmission coefficient kappaS which is not too
      small. In particular, the TST dividing surface must be optimized upon (for
      otherwise kappaS is generally very small), but this may not be sufficient to make
      the procedure numerically efficient (because the optimal dividing surface has
      maximum kappaS, but this coefficient may still be very small).

PMID- 16292896
TI  - Two-dimensional cross-spectral correlation analysis and its application to time
      resolved Fourier transform emission spectra of transient radicals.
AB  - A spectral analysis method, based on the generalized two-dimensional (2D)
      vibrational spectra correlation analysis, is developed for deciphering the
      correlation among the spectral peaks of two different spectra. This 2D cross
      spectral correlation (2DCSC) analysis is aimed at revealing the vibrational
      features associated with a common species in two spectra, each obtained from a
      system containing multiple species with at least one common species. The cross
      spectral correlation is based on the premise that the spectral features of the
      same species should have the same time and frequency responses toward similar
      perturbations. The effectiveness of the cross-spectral correlation analysis is
      first illustrated with model systems, with spectral peaks decaying linearly or
      exponentially with time, before being applied to analyzing time-resolved emission
      spectra obtained, by a Fourier transform IR spectrometer, for samples consisting
      of the vibrationally excited transient cyanooxomethyl radical (OCCN). 2DCSC among
      the three different sets of time-resolved spectra collected following the
      photodissociation of three different precursor molecules of OCCN, respectively,
      allows the identification of the CN and CO stretching modes of this radical.

PMID- 16292897
TI  - Relativistic DMRG calculations on the curve crossing of cesium hydride.
AB  - Over the past few years, it has been shown in various studies on small molecules
      with only a few electrons that the density-matrix renormalization group (DMRG)
      method converges to results close to the full configuration-interaction limit for
      the total electronic energy. In order to test the capabilities of the method for
      molecules with complex electronic structures, we performed a study on the
      potential-energy curves of the ground state and the first excited state of
      1sigma+ symmetry of the cesium hydride molecule. For cesium relativistic effects
      cannot be neglected, therefore we have used the generalized arbitrary-order
      Douglas-Kroll-Hess protocol up to tenth order, which allows for a complete
      decoupling of the Dirac Hamiltonian. Scalar-relativistic effects are thus fully
      incorporated in the calculations. The potential curves of the cesium hydride
      molecule feature an avoided crossing between the ground state and the first
      excited state, which is shown to be very well described by the DMRG method.
      Compared to multireference configuration-interaction results, the potential
      curves hardly differ in shape, for both the ground state and the excited state,
      but the total energies from the DMRG calculations are in general consistently
      lower. However, the DMRG energies are as accurate as corresponding coupled
      cluster energies at the equilibrium distance, but convergence to the full
      configuration-interaction limit is not achieved.

PMID- 16292898
TI  - Weak intermolecular interactions calculated with diffusion Monte Carlo.
AB  - The performance of fixed node diffusion Monte Carlo (FNDMC) for weakly
      interacting molecules is investigated. The effect of Gaussian basis sets on the
      asymptotic description of the molecular orbitals which is crucial for a
      successful importance sampling is analyzed for the example of the hydrogen atom.
      We find that accurate reference binding energies of the water, the ammonia, and
      the T-shaped as well as the parallel-displaced benzene dimer are correctly
      reproduced by FNDMC. The binding energies for the benzene dimers are -3.00(0.38)
      and -3.58(0.38) kcal/mol, respectively. The description of the methane dimer
      which has the smallest binding energy and a quite large intermolecular distance
      requires a more flexible basis set of diffuse quadruple-zeta quality in order to
      prevent sampling errors.

PMID- 16292899
TI  - The accuracy of ab initio molecular geometries for systems containing second-row
      atoms.
AB  - The performance of the standard hierarchy of ab initio models--that is, Hartree
      Fock theory, second-order Moller-Plesset theory, coupled-cluster singles-and
      doubles theory, and coupled-cluster singles-doubles-approximate-triples theory-
      in combination with correlation-consistent basis sets is investigated for
      equilibrium geometries of molecules containing second-row elements. From an
      analysis on a collection of 31 molecules (yielding statistical samples of 41 bond
      distances and 13 bond angles), the statistical errors (mean deviation, mean
      absolute deviation, standard deviation, and maximum absolute deviation) are
      established at each level of theory. The importance of core correlation is
      examined by comparing calculations in the frozen-core approximation with
      calculations where all electrons are correlated.

PMID- 16292900
TI  - Calculations of two-photon charge-transfer excitations using Coulomb-attenuated
      density-functional theory.
AB  - In this work, we show that an implementation of Coulomb-attenuated density
      functional theory leads to considerably better prospects than hitherto for
      modeling two-photon absorption cross sections for charge-transfer species. This
      functional, which corrects for the effect of poor asymptotic dependence of
      commonly used functionals, essentially brings down the widely different results
      for larger charge-transfer species between Hartree-Fock and density-functional
      theory (DFT)-B3LYP into a closer range. The Coulomb-attenuated functional, which
      retains the best aspects of the Hartree-Fock and DFT-B3LYP methods, proves to be
      very promising for further modeling design of multiphoton materials with
      technical applications.

PMID- 16292901
TI  - The interaction of C6H6 and C6H12 with noble metal surfaces: electronic level
      alignment and the origin of the interface dipole.
AB  - The electronic interaction of two molecules, the aromatic benzene (C6H6) and the
      saturated hydrocarbon cyclohexane (C6H12) with a Cu(111) surface, have been
      determined using precise, ab initio electronic structure calculations. For the
      interaction of these adsorbates with the substrate, we present a detailed
      analysis and decomposition of various individual chemical mechanisms that
      contribute. A novel aspect of this analysis is the use of charge-density
      difference contour plots to graphically display the chemistry. A wave-function
      based approach was used in order to avoid problems when the presently most
      commonly employed approach, density-functional theory, is applied to weakly
      chemisorbed molecules, where the interaction is dominated by van der Waals
      forces. The present information are not only relevant with regard to
      understanding the chemistry going on when molecules are adsorbed on a Cu surface
      but also have important consequences with regard to charge injection in molecular
      electronic devices, e.g., organic field-effect transistors and organic light
      emitting diodes.

PMID- 16292902
TI  - Phase-space reaction network on a multisaddle energy landscape: HCN
      isomerization.
AB  - By using the HCN/CNH isomerization reaction as an illustrative vehicle of
      chemical reactions on multisaddle energy landscapes, we give explicit
      visualizations of molecular motions associated with a straight-through reaction
      tube in the phase space inside which all reactive trajectories pass from one
      basin to another, with eliminating recrossing trajectories in the configuration
      space. This visualization provides us with a chemical intuition of how chemical
      species "walk along" the reaction-rate slope in the multidimensional phase space
      compared with the intrinsic reaction path in the configuration space. The
      distinct nonergodic features in the two different HCN and CNH wells can be easily
      demonstrated by a section of Poincare surface of section in those potential
      minima, which predicts in a priori the pattern of trajectories residing in the
      potential well. We elucidate the global phase-space structure which gives rise to
      the non-Markovian dynamics or the dynamical correlation of sequential multisaddle
      chemical reactions. The phase-space structure relevant to the controllability of
      the product state in chemical reactions is also discussed.

PMID- 16292903
TI  - Ab initio calculation of the NH(3sigma-)-NH(3sigma-) interaction potentials in
      the quintet, triplet, and singlet states.
AB  - We present the ab initio potential-energy surfaces of the NH-NH complex that
      correlate with two NH molecules in their 3sigma- electronic ground state. Three
      distinct potential-energy surfaces, split by exchange interactions, correspond to
      the coupling of the S(A) = 1 and S(B) = 1 electronic spins of the monomers to
      dimer states with S = 0, 1, and 2. Exploratory calculations on the quintet (S =
      2), triplet (S = 1), and singlet (S = 0) states and their exchange splittings
      were performed with the valence bond self-consistent-field method that explicitly
      accounts for the nonorthogonality of the orbitals on different monomers. The
      potential surface of the quintet state, which can be described by a single Slater
      determinant reference function, was calculated at the coupled cluster level with
      single and double excitations and noniterative treatment of the triples. The
      triplet and singlet states require multiconfiguration reference wave functions
      and the exchange splittings between the three potential surfaces were calculated
      with the complete active space self-consistent-field method supplemented with
      perturbative configuration interaction calculations of second and third orders.
      Full potential-energy surfaces were computed as a function of the four
      intermolecular Jacobi coordinates, with an aug-cc-pVTZ basis on the N and H atoms
      and bond functions at the midpoint of the intermolecular vector R. An analytical
      representation of these potentials was given by expanding their dependence on the
      molecular orientations in coupled spherical harmonics, and representing the
      dependence of the expansion coefficients on the intermolecular distance R by the
      reproducing kernel Hilbert space method. The quintet surface has a van der Waals
      minimum of depth D(e) = 675 cm(-1) at R(e) = 6.6a0 for a linear geometry with the
      two NH electric dipoles aligned. The singlet and triplet surfaces show similar,
      slightly deeper, van der Waals wells, but when R is decreased the weakly bound NH
      dimer with S = 0 and S = 1 converts into the chemically bound N2H2 diimide (also
      called diazene) molecule with only a small energy barrier to overcome.

PMID- 16292904
TI  - Dissociation processes of Kr2(+) and Kr3(+) studied by threshold photoelectron
      photoion coincidence measurements.
AB  - A time-of-flight (TOF) ion mass spectrum in coincidence with threshold
      photoelectrons was measured in the photon energy region between the first and
      second dissociation limits of Kr2(+) to examine the decay processes of the Kr2(+)
      II(1/2u) state. The measured TOF spectrum reveals that Kr+ fragment ions are
      produced through dissociation of the repulsive I(1/2g) state, which can be formed
      by the decay process of the II(1/2u) state accompanied with emission of photons.
      The potential-energy curve of the I(1/2g) state is deduced with detailed analysis
      of the observed TOF spectrum, in which the radiative lifetime of the II(1/2u)
      state was also derived to be 2.5 micros. Additionally, evidence of the
      dissociation process of Kr3(+) ions was obtained in the same photon energy
      region, where the dominant channel is Kr3(+) --> Kr2(+) + Kr.

PMID- 16292905
TI  - Extensive ab initio study of the electronic states of SCl including spin-orbit
      coupling.
AB  - The effect of different basis sets for calculation of the spectroscopic constants
      of the ground state of sulfur monochloride (SCl) was analyzed using scalar
      relativistic multireference configuration interaction with single and double
      excitations plus Davidson correction. Then the generally contracted all
      electronic correlation-consistent polarized valence quintuple zeta basis sets
      were selected to compute the electronic states of SCl including 12 valence and 9
      Rydberg lambda-S states. The spin-orbit coupling effect was calculated via the
      state interaction approach with the full Breit-Pauli Hamiltonian. This effect
      splits these lambda-S states into 42 omega states. Potential-energy curves of all
      these states are plotted with the help of the avoided crossing rule between the
      electronic states of the same symmetry. The structural properties of these states
      are analyzed. Spectroscopic constants of bound excited states that have never
      been observed in experiment are obtained. The transition dipole moments and the
      Franck-Condon factors of several transitions from low-lying bound excited states
      to the ground state were also calculated.

PMID- 16292906
TI  - Selective OD bond dissociation of HOD: photodissociation of vibrationally excited
      HOD in the 5nu(OD) state.
AB  - Exclusively selective OD bond dissociation of HOD has been demonstrated by the
      ultraviolet photodissociation at 243.1 nm through the fourth overtone state of
      the OD stretching mode (5nu(OD)). Branching ratio between the OH and OD bond
      dissociation channels has been determined by detecting H and D atoms, utilizing a
      (2+1) resonance-enhanced multiphoton ionization (REMPI) process. The OD bond
      dissociation has been solely observed with the branching ratio
      phi(D+OH)/phi(H+OD)>12, which has been determined by the detection limit for the
      H atom. Time-dependent wave-packet calculations reveal two important features for
      the highly selective OD bond dissociation: (1) strong local-mode character of the
      5nu(OD) state and (2) limitation of the total excitation energy lower than the
      saddle point between the OH and OD dissociation channels in the A state.
      Additionally, the recoil velocity and angular distribution of the nascent D atom
      are roughly evaluated by analyzing the Doppler-resolved REMPI spectrum. Based on
      these results, the dynamics of the selective OD dissociation has been discussed
      in detail.

PMID- 16292907
TI  - Structure and electronic properties of highly charged C60 and C58 fullerenes.
AB  - We present a theoretical study of the structure and electronic properties of
      positively charged C60(q+) and C58(q+) fullerenes (q = 0-14). Electronic energies
      and optimum geometries have been obtained using density-functional theory with
      the B3LYP functional for exchange and correlation. We have found that closed- and
      semiclosed-shell C60(q+) ions (q = 0, 5, and 10) preserve the original
      icosahedral symmetry of neutral C60. For other charges, significant distortions
      have been obtained. The C58(q+) fullerenes are, in general, less symmetric, being
      C58(8+) the closest to the spherical shape. Most C60(q+) fullerenes follow Hund's
      rule for spin multiplicity, while most C58(q+) fullerenes are more stable with
      the lowest spin multiplicity. The calculated ionization potentials for both kinds
      of fullerenes increase almost linearly with charge, except in the vicinity of
      C60(10+) and C58(8+). We have also explored the region of the potential-energy
      surface of C60(q+) that leads to asymmetric fission. Minima and transition states
      corresponding to the last steps of the fission process have been obtained. This
      has led us to conclude that, for 3 < or = q < or = 8, C2(+) emission is the
      preferred fragmentation channel, whereas, for higher q values, emission of two
      charged atomic fragments is more favorable. The corresponding fission barrier
      vanishes for q > 14.

PMID- 16292908
TI  - Why is hydrofluoric acid a weak acid?
AB  - The infrared vibrational spectra of amorphous solid water thin films doped with
      HF at 40 K reveal a strong continuous absorbance in the 1000-3275 cm(-1) range.
      This so-called Zundel continuum is the spectroscopic hallmark for aqueous
      protons. The extensive ionic dissociation of HF at such low temperature suggests
      that the reaction enthalpy remains negative down to 40 K. These observations
      support the interpretation that dilute HF aqueous solutions behave as weak acids
      largely due to the large positive reaction entropy resulting from the structure
      making character of the hydrated fluoride ion.

PMID- 16292909
TI  - A new insight on the structural changes of linear quadrupole liquids.
AB  - Molecular-dynamics simulations for linear quadrupole liquids are presented. The
      study is carried out for two different molecular lengths at constant density and
      a number of temperatures and quadrupole moments. All the simulated thermodynamic
      states correspond to the condensed phases and some of them show typical features
      of a solid structure. Furthermore, a change on the preferred intermolecular
      orientation in the liquid phase is observed from a shifted parallel molecular
      arrangement to a perpendicular orientation as the quadrupole raises. This change
      depends on the quadrupole moment as well as on the molecular length and is put in
      relation with the solid structure of different "diatomic" molecules such as
      nitrogen, ethane, and acetylene. The appearance of a plastic solid phase at low
      quadrupole moment and density is also justified. A thoroughly discussion about
      the availability of classical perturbation theories for this kind of systems is
      presented.

PMID- 16292910
TI  - Investigating pressure effects on structural and dynamical properties of liquid
      methanol with many-body interactions.
AB  - Molecular-dynamics simulations utilizing a many-body potential was used to study
      the pressure dependence of structural and dynamical properties for liquid
      methanol. The liquid density as a function of pressure agreed well with
      experiment, and a combination of radial and angular distribution functions were
      used to analyze molecular structure. From these distribution functions, it was
      observed that hydrogen bond strength increased with increasing pressure. This
      observation coincided with an increase in the molecular dipole as a function of
      pressure, having a significant effect on the observed increased hydrogen bond
      strength. Also, methanols were found to more strongly favor exactly two hydrogen
      bonds, with fewer methanols of zero, one, or three hydrogen bonds present at
      higher pressures. Furthermore, a majority of the compression with increased
      pressure was found to occur in regions perpendicular to the methanol hydrogen
      oxygen bond vector. This was the case despite hydrogen-oxygen nonbonded distances
      between hydrogen bonding species being shorter, but their stiffer oxygen-hydrogen
      (nonbonded) oxygen angle offsets this, resulting in their oxygen-oxygen distances
      being relatively unaffected. The methanol translational diffusion decreased
      significantly with increased pressure, while the rotational diffusion decreased
      at a similar magnitude around the oxygen-hydrogen and oxygen-carbon bond vectors,
      despite having very different overall diffusion. Finally, the hydrogen bond
      lifetime increased significantly with pressure, owing to the increased hydrogen
      bond strength, and the slower translational and rotational dynamics.

PMID- 16292911
TI  - Global thermodynamics of hydrophobic cavitation, dewetting, and hydration.
AB  - Pure water experimental and simulation results are combined to predict the
      thermodynamics of cavity formation, spanning atomic to macroscopic length scales,
      over the entire ambient liquid temperature range. The resulting cavity equation
      of state is used to quantify dewetting excess contributions to cavity formation
      thermodynamics and construct a thermodynamic perturbation theory of hydrophobic
      hydration. Predictions are compared with large cavity simulations and
      experimental rare-gas hydration thermodynamics data (for He, Ne, Ar, Kr, Xe, and
      Rn). Key findings include the strong temperature dependence of the critical
      length scale for hydrophobic dewetting and the evaluation of fundamental solute
      solvent interaction contributions to rare-gas hydration chemical potentials.

PMID- 16292912
TI  - Collision as a way of forming bimetallic nanoclusters of various structures and
      chemical compositions.
AB  - In the present work, a new way to obtain bimetallic nanoclusters of different
      structures and chemical compositions is proposed, which is based on computer
      simulations. Collision processes between two metal clusters of different natures
      are simulated through molecular-dynamics simulations using many-body potentials.
      Diverse diffusion mechanisms and structures can be observed, depending on the
      metals combined and the initial kinetic energies. The nanostructures we have
      found are core-shell (Pt-Au), alloyed (Pd-Au), and three-shell onionlike (Cu-Ag).

PMID- 16292913
TI  - Transport properties of normal liquid helium: comparison of various
      methodologies.
AB  - We revisit the problem of self-diffusion in normal liquid helium above the lambda
      transition. Several different methods are applied to compute the velocity
      autocorrelation function. Since it is still impossible to determine the exact
      result for the velocity autocorrelation function from simulation, we appeal to
      the computation of short-time moments to determine the accuracy of the different
      approaches at short times. The main conclusion reached from our study is that
      both the quantum mode-coupling theory and the numerical analytic continuation
      approach must be regarded as a viable and competitive methods for the computation
      of dynamical properties of quantum systems.

PMID- 16292914
TI  - Phase and interfacial behavior of partially miscible symmetric Lennard-Jones
      binary mixtures.
AB  - We have carried out extensive equilibrium molecular-dynamics simulations to study
      quantitatively the topology of the temperature versus density phase diagrams and
      related interfacial phenomena in a partially miscible symmetric Lennard-Jones
      binary mixture. The topological features are studied as a function of miscibility
      parameter, alpha = epsilonAB/epsilonAA. Here epsilonAA = epsilonBB and epsilonAB
      stand for the parameters related to the attractive part of the intermolecular
      interactions for similar and dissimilar particles, respectively. When the
      miscibility varies in the range 0 < alpha < 1, a continuous critical line of
      consolute points Tcons(rho)--critical demixing transition line--appears. This
      line intersects the liquid-vapor coexistence curve at different positions
      depending on the values of alpha, yielding mainly three different topologies for
      the phase diagrams. These results are in qualitative agreement to those found
      previously for square-well and hard-core Yukawa binary mixtures. The main
      contributions of the present paper are (i) a quantitative analysis of the phase
      behavior and (ii) a detailed study of the liquid-liquid interfacial and liquid
      vapor surface tensions, as function of temperature and miscibility as well as its
      relationship to the topological features of the phase diagrams.

PMID- 16292916
TI  - Current-induced rotation of helical molecular wires.
AB  - We show that electric current running through a nanojunction with a biased
      helical molecule can induce unidirectional rotation of the molecular component.
      In an electric field, conduction electrons injected into the molecule are
      accelerated along the helical path going through its body, thereby gaining
      directed angular momentum. Conservation laws require that an angular momentum of
      the same size but opposite sense is imparted to the rigid-body rotation of the
      helix. We describe the angular momentum exchange processes that underlie the
      operation of the nanorotor, discuss factors limiting its efficiency, and propose
      potential applications.

PMID- 16292915
TI  - Size-controlled synthesis and characterization of thiol-stabilized gold
      nanoparticles.
AB  - Size-controlled synthesis of nanoparticles of less than a few nanometers in size
      is a challenge due to the spatial resolution limit of most scattering and imaging
      techniques used for their structural characterization. We present the self
      consistent analysis of the extended x-ray absorption fine-structure (EXAFS)
      spectroscopy data of ligand-stabilized metal nanoclusters. Our method employs the
      coordination number truncation and the surface-tension models in order to measure
      the average diameter and analyze the structure of the nanoparticles. EXAFS
      analysis was performed on the two series of dodecanethiol-stabilized gold
      nanoparticles prepared by one-phase and two-phase syntheses where the only
      control parameter was the gold/thiol ratio xi, varied between 6:1 and 1:6. The
      two-phase synthesis resulted in the smaller particles whose size decreased
      monotonically and stabilized at 16 A when xi was lowered below 1:1. This behavior
      is consistent with the theoretically predicted thermodynamic limit obtained
      previously in the framework of the spherical drop model of Au nanoparticles.

PMID- 16292917
TI  - Optoelectronic properties analysis of Ti-substituted GaP.
AB  - A study using first principles of the electronic and optical properties of
      materials derived from a GaP host semiconductor where one Ti atom is substituted
      for one of the eight P atoms is presented. This material has a metallic
      intermediate band sandwiched between the valence and conduction bands of the host
      semiconductor for 0 < or = U < or = 8 eV where U is the Hubbard parameter. The
      potential of these materials is that when they are used as an absorber of photons
      in solar cells, the efficiency is increased significantly with respect to that of
      the host semiconductor. The results show that the main contribution to the
      intermediate band is the Ti atom and that this material can absorb photons of
      lower energy than that of the host semiconductor. The efficiency is increased
      with respect to that of the host semiconductor mainly because of the absorption
      from the intermediate to conduction band. As U increases, the contribution of the
      Ti-d orbitals to the intermediate band varies, increasing the d(z2) character at
      the bottom of the intermediate band.

PMID- 16292918
TI  - Histogram analysis as a method for determining the line tension of a three-phase
      contact region by Monte Carlo simulations.
AB  - A method is proposed for determining the line tension, which is the main physical
      characteristic of a three-phase contact region, by Monte Carlo (MC) simulations.
      The key idea of the proposed method is that if a three-phase equilibrium involves
      a three-phase contact region, the probability distribution of states of a system
      as a function of two order parameters depends not only on the surface tension,
      but also on the line tension. This probability distribution can be obtained as a
      normalized histogram by appropriate MC simulations, so one can use the
      combination of histogram analysis and finite-size scaling to study the properties
      of a three phase contact region. Every histogram and results extracted therefrom
      will depend on the size of the simulated system. Carrying out MC simulations for
      a series of system sizes and extrapolating the results, obtained from the
      corresponding series of histograms, to infinite size, one can determine the line
      tension of the three phase contact region and the interfacial tensions of all
      three interfaces (and hence the contact angles) in an infinite system. To
      illustrate the proposed method, it is applied to the three-dimensional ternary
      fluid mixture, in which molecular pairs of like species do not interact whereas
      those of unlike species interact as hard spheres. The simulated results are in
      agreement with expectations.

PMID- 16292919
TI  - Interaction of coadsorbed CH3Cl and D2O layers on Pd(111) studied by sum
      frequency generation.
AB  - Adsorption of methyl chloride and coadsorption of CH3Cl and D2O on Pd(111)
      surfaces at T=100 K have been studied under ultrahigh-vacuum conditions using
      femtosecond sum frequency generation (SFG) spectroscopy in the spectral regions
      of CH and OD bands. On the bare Pd(111) substrate, the CH3Cl coverage dependence
      of the resonant SFG signal is consistent with a progressive molecular
      rearrangement starting at half saturation followed by the growth of two ordered
      monolayers in which the molecular axes are perpendicular to the surface. When
      CH3Cl is adsorbed on top of predeposited D2O on Pd(111), the SFG signals as a
      function of the CH3Cl exposure indicate that methyl chloride is adsorbed onto D2O
      through hydrogen bonding. On the contrary when the adsorption order is reversed
      the strong decrease of the CH3 signal as a function of the D2O exposure is
      explained by assuming that water molecules penetrate inside the CH3Cl layers,
      leading to the formation of disordered CH3Cl clusters. In all cases a nonresonant
      contribution due to molecular adsorption is observed and it shows a dependence
      upon surface structure and coverage significantly different from that of the
      resonant vibrational bands.

PMID- 16292920
TI  - Liquid-vapor interfaces of water-acetonitrile mixtures of varying composition.
AB  - Detailed molecular-dynamics simulations are carried out to investigate the
      equilibrium and dynamical properties of water-acetonitrile mixtures of varying
      composition. Altogether, we have simulated eight different systems of different
      concentrations of acetonitrile. The inhomogeneous density and anisotropic
      orientational profiles at interfaces, surface tension, and also the distribution
      of hydrogen bonds are calculated for both water and acetonitrile molecules. The
      dynamical aspects of the interfaces are investigated in terms of the anisotropic
      diffusion and dipole orientational relaxation of interfacial water and
      acetonitrile molecules. For both structural and dynamical properties, the
      behaviors of the interfaces are compared with those of the corresponding bulk
      phases. A comparison between the present theoretical results and experimental
      findings, wherever available, is also made to verify the usefulness of the
      molecular models employed in the present study for predicting interfacial
      properties.

PMID- 16292921
TI  - The role of molecular interactions and interfaces in diffusion: transport
      diffusivity and evaluation of the Darken approximation.
AB  - Kinetic Monte Carlo (KMC) simulations are carried out to directly study diffusion
      of benzene through thin (37-100 nm) NaX zeolite membranes under a gradient in
      chemical potential. Nonlinearities in adsorbate loading near the membrane
      boundaries are shown to arise from the difference in adsorbate density between
      the zeolite and adjacent fluid phase. Direct extraction of the transport
      diffusivity from gradient KMC simulations enables testing of the Darken
      approximation. This rigorous approach reveals limitations of the Darken
      approximation and, for the first time, the potentially complex nonunique
      functionality and multiplicity of the transport diffusivity for strongly
      interacting adsorbates. In the companion paper we explore these nonlinear
      interfacial effects in the context of permeation through both single-crystal and
      polycrystalline membranes.

PMID- 16292922
TI  - The role of molecular interactions and interfaces in diffusion: permeation
      through single-crystal and polycrystalline microporous membranes.
AB  - In this second paper of a two part series, we investigate the implications of the
      interfacial phenomenon, caused by adsorbate-adsorbate interactions coupled with
      the difference in adsorbate density between the zeolite and the gas phase, upon
      benzene permeation through single-crystal and polycrystalline microporous NaX
      membranes. The high flux predicted for thin single-crystal membranes reveals that
      substantially enhanced flux should be expected in submicron films. Simulations
      also indicate that the standard local equilibrium assumption made for larger
      scale membranes is inapplicable at the submicron scale associated with nanometer
      size grains of thin and/or polycrystalline membranes. Apparent activation
      energies predicted for benzene permeation through NaX membranes via kinetic Monte
      Carlo (KMC) simulations are in good agreement with laboratory experiments. The
      simulations also uncover temperature-dependent flux pathways leading to non
      Arrhenius behavior observed experimentally. The failure of the Darken
      approximation, especially in the presence of the interfacial phenomenon, leads to
      a substantial overprediction of the flux. Simulations of polycrystalline
      membranes suggest that this same interfacial phenomenon leads to resistance that
      can reduce flux by an order of a magnitude with only moderate polycrystallinity.

PMID- 16292923
TI  - Vibron-polaron in alpha-helices. I. Single-vibron states.
AB  - The vibron dynamics associated to amide-I vibrations in a three-dimensional alpha
      helix is described according to a generalized Davydov model. The helix is modeled
      by three spines of hydrogen-bonded peptide units linked via covalent bonds. To
      remove the intramolecular anharmonicity of each amide-I mode and to renormalize
      the vibron-phonon coupling, two unitary transformations have been applied to
      reach the dressed anharmonic vibron point of view. It is shown that the vibron
      dynamics results from the competition between interspine and intraspine vibron
      hops and that the two kinds of hopping processes do not experience the same
      dressing mechanism. Therefore, at low temperature (or weak vibron-phonon
      coupling), the polaron behaves as an undressed vibron delocalized over all the
      spines whereas at biological temperature (or strong vibron-phonon coupling), the
      dressing effect strongly reduces the vibrational exchanges between different
      spines. As a result the polaron propagates along a single spine as in the one
      dimensional Davydov model. Although the helix supports both acoustical and
      optical phonons, this feature originates in the coupling between the vibron and
      the acoustical phonons only. Finally, the lattice distortion which accompanies
      the polaron has been determined and it is shown that residues located on the
      excited spine are subjected to a stronger deformation than the other residues.

PMID- 16292924
TI  - Vibron-polaron in alpha-helices. II. Two-vibron bound states.
AB  - The two-vibron dynamics associated to amide-I vibrations in a three-dimensional
      (3D) alpha-helix is described according to a generalized Davydov model. The helix
      is modeled by three spines of hydrogen-bonded peptide units linked via covalent
      bonds. It is shown that the two-vibron energy spectrum supports both a two-vibron
      free states continuum and two kinds of bound states, called two-vibron bound
      states (TVBS)-I and TVBS-II, connected to the trapping of two vibrons onto the
      same amide-I mode and onto two nearest-neighbor amide-I modes belonging to the
      same spine, respectively. At low temperature, nonvanishing interspine hopping
      constants yield a three-dimensional nature of both TVBS-I and TVBS-II which the
      wave functions extend over the three spines of the helix. At biological
      temperature, the pairs are confined in a given spine and exhibit the same
      features as the bound states described within a one-dimensional model. The
      interplay between the temperature and the 3D nature of the helix is also
      responsible for the occurrence of a third bound state called TVBS-III which
      refers to the trapping of two vibrons onto two different spines. The experimental
      signature of the existence of bound states is discussed through the simulation of
      their infrared pump-probe spectroscopic response. Finally, the fundamental
      question of the breather-like behavior of two-vibron bound states is addressed.

PMID- 16292925
TI  - Ab initio electron propagator theory of molecular wires. I. Formalism.
AB  - Ab initio electron propagator methodology may be applied to the calculation of
      electrical current through a molecular wire. A new theoretical approach is
      developed for the calculation of the retarded and advanced Green functions in
      terms of the electron propagator matrix for the bridge molecule. The calculation
      of the current requires integration in a complex half plane for a trace that
      involves terminal and Green's-function matrices. Because the Green's-function
      matrices have complex poles represented by matrices, a special scheme is
      developed to express these "matrix poles" in terms of ordinary poles. An
      expression for the current is derived for a terminal matrix of arbitrary rank.
      For a single terminal orbital, the analytical expression for the current is given
      in terms of pole strengths, poles, and terminal matrix elements of the electron
      propagator. It is shown that Dyson orbitals with high pole strengths and overlaps
      with terminal orbitals are most responsible for the conduction of electrical
      current.

PMID- 16292926
TI  - Nonequilibrium electronic transport of 4,4'-bipyridine molecular junction.
AB  - The electronic transport properties of a 4,4'-bipyridine molecule sandwiched
      between two Au(111) surfaces are studied with a fully self-consistent
      nonequilibrium Green's-function method combined with the density-functional
      theory. The 4,4'-bipyridine molecule prefers to adsorb near the hollow site of
      the Au(111) surface and distorts slightly. The modifications on the electronic
      structure of the molecule due to the presence of the electrodes are described by
      the renormalized molecular orbitals, which correspond well to the calculated
      transmission peaks. The average Fermi level lies close to the lowest unoccupied
      renormalized molecular orbital, which determines the electronic transport
      property of the molecular junction under a small bias voltage. The total
      transmission is contributed by a single channel. The transmission peaks shift
      with the applied bias voltage, and this behavior depends on the spatial
      distribution of the renormalized molecular orbitals and the voltage drop along
      the molecular junction. The shape of the calculated conductance curve of the
      equilibrium geometric configuration reproduces the main feature of the
      experimental results, but the value is larger than the measured data by about 6
      times. Good agreement with the experimental measurements can be obtained by
      elongating the molecular junction. The electronic transport behaviors depend
      strongly on the interface configuration.

PMID- 16292927
TI  - The reaction kinetics of Cu with the CdTe(111)-B surface: formation of metastable
      Cu(x)Te (x approximately 2).
AB  - In the present study, elemental Cu is deposited on the clean CdTe(111)-B surface
      and annealed in vacuum. Surface-composition maps generated by scanning Auger
      microcopy provide evidence that a reaction occurs between Cu and the CdTe(111)-B
      substrate that results in the formation of a metastable copper telluride phase
      Cu(x)Te (x approximately 2) at the surface. In situ thermal-desorption mass
      spectrometry measurements show that elemental Cd is released during the reaction
      and desorbs from the surface. Desorption of Te from the substrate is suppressed
      during the reaction. Analysis of Cd desorption traces demonstrates that the Cu +
      CdTe(111)-B reaction proceeds via zero-order kinetics, with an activation energy
      of 180 +/- 5 kJ mol(-1).

PMID- 16292928
TI  - A molecular-dynamics study of lipid bilayers: effects of the hydrocarbon chain
      length on permeability.
AB  - In this paper, we investigate the effects of the hydrocarbon chain length of
      lipid molecules on the permeation process of small molecules through lipid
      bilayers. We perform molecular-dynamics simulations using three kinds of lipid
      molecules with different chain length: dilauroylphosphatidylcholine,
      dimyristoylphosphatidylcholine, and dipalmiltoylphosphatidylcholine. Free-energy
      profiles of O2, CO, NO, and water molecules are calculated by means of the cavity
      insertion Widom method and the probability ratio method. We show that the lipid
      membrane with longer chains has a larger and wider energy barrier. The local
      diffusion coefficients of water across the bilayers are also calculated by the
      force autocorrelation function method and the velocity autocorrelation function
      method. The local diffusion coefficients in the bilayers are not altered
      significantly by the chain length. We estimate the permeability coefficients of
      water across the three membranes according to the solubility-diffusion model; we
      find that the water permeability decreases modestly with increasing chain length
      of the lipid molecules.

PMID- 16292929
TI  - Production of oxygen by electronically induced dissociations in ice.
AB  - A solid-state chemical model is given for the production of O2 by electronic
      excitation of ice, a process that occurs on icy bodies in the outer solar system.
      Based on a review of the relevant available laboratory data, we propose that a
      trapped oxygen atom-water complex is the principal precursor for the formation of
      molecular oxygen in low-temperature ice at low fluences. Oxygen formation then
      occurs through direct excitation of this complex or by its reaction with a
      freshly produced, nonthermal O from an another excitation event. We describe a
      model for the latter process that includes competition with precursor destruction
      and the effect of sample structure. This allows us to put the ultraviolet photon,
      low-energy electron, and fast-ion experiments on a common footing for the first
      time. The formation of the trapped oxygen atom precursor is favored by the
      preferential loss of molecular hydrogen and is quenched by reactions with mobile
      H. The presence of impurity scavengers can limit the trapping of O, leading to
      the formation of oxygen-rich molecules in ice. Rate equations that include these
      reactions are given and integrated to obtain an analytic approximation for
      describing the experimental results on the production and loss of molecular
      oxygen from ice samples. In the proposed model, the loss rate varies, roughly,
      inversely with solid-state defect density at low temperatures, leading to a yield
      that increases with increasing temperature as observed. Cross sections obtained
      from fits of the model to laboratory data are evaluated in light of the proposed
      solid-state chemistry.

PMID- 16292930
TI  - Adsorption of CO on the copper-precovered ZnO(0001) surface: a molecular-beam
      scattering study.
AB  - Auger electron spectroscopy (AES), thermal-desorption spectroscopy (TDS), and, in
      particular, molecular-beam scattering techniques have been combined to address
      particle size effects in the adsorption of CO on Cu-on-ZnO(0001). AES and TDS
      lead to a Cu coverage, theta(Cu), calibration. The TDS curves, as a function of
      theta(Cu) and CO exposure, revealed three structures at 150, 220, and 260-280 K,
      in agreement with prior studies. However, a unique assignment of the TDS
      structures to a particular Cu face was not possible. An enhancement of the
      initial adsorption probability, S0, with respect to the support indicates the
      effect of the Cu nanoparticles. Despite that the shape of S0 versus impact energy
      curves was independent of theta(Cu) and agreed with Cu single-crystal reference
      systems, distinct particle size effects were present with regard to the
      adsorption mechanism. It was possible to observe a crossover from Langmuir-type
      adsorption dynamics to more precursor-assisted adsorption dynamics with
      increasing theta(Cu). Thus, a dynamic structure-activity relationship was
      evident, i.e., the energy-transfer mechanism depends on the Cu morphology.

PMID- 16292931
TI  - Electronic structure of phospho-olivines Li(x)FePO4 (x = 0, 1) from soft-x-ray
      absorption and -emission spectroscopies.
AB  - The electronic structure of the phospho-olivine Li(x)FePO4 was studied using soft
      x-ray-absorption (XAS) and emission spectroscopies. Characteristic changes in the
      valence and conduction bands are observed upon delithation of LiFePO4 into FePO4.
      In LiFePO4, the Fe-3d states are localized with little overlap with the O-2p
      states. Delithiation of LiFePO4 gives stronger hybridization between Fe-3d states
      and O-2p states leading to delocalization of the O-2p states. The Fe L-edge
      absorption spectra yield "fingerprints" of the different valence states of Fe in
      LiFePO4 and FePO4. Resonant soft-x-ray-emission spectroscopy at the Fe L edge
      shows strong contributions from resonant inelastic soft x-ray scattering (RIXS),
      which is described using an ionic picture of the Fe-3d states. Together the Fe L
      edge XAS and RIXS study reveals a bonding character of the Fe 3d-O2p orbitals in
      FePO4 in contrast to a nonbonding character in LiFePO4.

PMID- 16292932
TI  - Self-assembled morphologies of monotethered polyhedral oligomeric silsesquioxane
      nanocubes from computer simulation.
AB  - Self-assembly of functionalized nanoscale building blocks is a promising strategy
      for "bottom-up" materials design. Recent experiments have demonstrated that the
      self-assembly of polyhedral oligomeric silsesquioxane (POSS) "nanocubes"
      functionalized with organic tethers can be utilized to synthesize novel materials
      with highly ordered, complex nanostructures. We have performed molecular
      simulations for a simplified model of monotethered POSS nanocubes to investigate
      systematically how the parameters that control the assembly process and the
      resulting equilibrium structures, including concentration, temperature, tether
      lengths, and solvent conditions, can be manipulated to achieve useful structures
      via self-assembly. We report conventional lamellar and cylindrical structures
      that are typically found in block copolymer and surfactant systems, including a
      thermotropic order-order transition, but with interesting stabilization of the
      lamellar phase caused by the bulkiness and cubic geometry of the POSS nanocubes.

PMID- 16292933
TI  - Calculation of the circular dichroism spectra of carbon monoxy- and deoxy
      myoglobin: interpretation of a time-resolved circular dichroism experiment.
AB  - A calculation of the circular dichroism (CD) spectra of carbon monoxy- and deoxy
      myoglobin is carried out in relation with a time-resolved CD experiment. The
      calculation is based on the polarizability theory and the parameters are adjusted
      to fit the experimental absorption and CD spectra. By performing the calculation
      for intermediate configurations of the protein, we are able to propose an
      explanation of the CD structure observed on a sub-100 ps time scale. The role of
      the proximal histidine is, in particular, clearly demonstrated in the first step
      of the myoglobin relaxation from its liganded to it deliganded form.

PMID- 16292934
TI  - Asymptotic trends in thermodynamic perturbation theory.
AB  - The development of transferable force fields for n-alkanes has enabled molecular
      dynamics simulation of the reference (A0) and perturbation (A1,A2) terms in
      thermodynamic perturbation theory (TPT) over a broad range of chain length. The
      implied equations of state yield 9.1% average error in vapor pressure and 4.7%
      error in liquid density for compounds ranging from propane to triacontane.
      Further simulations extend to nC80, but there are no experimental data to which
      comparisons can be made. With reliable TPT terms from molecular simulation, it is
      possible to analyze the trends with respect to molecular weight. Each TPT
      contribution is shown to approach an asymptote in the long chain limit. The
      asymptotes and the approaches to them are quantitatively characterized. A0 and A1
      approach their asymptotes at relatively short chain lengths (nC30). A2, on the
      other hand, approaches its asymptote slowly (nC80). Simulation-based TPT terms
      also permit unambiguous interpretation of the number of coarse-grained segments
      relative to the number of carbons in the chain. Previous attempts have relied on
      characterizations that included the repulsive and attractive contributions
      simultaneously in a manner susceptible to a cancellation of errors. In this work,
      the reference fluid alone provides the characterization and the result is shown
      to be consistent with expectations for the A1 term. The conclusion is that the
      number of carbons per segment approaches roughly 10 in the long chain limit, much
      larger than previously reported. A small adjustment to the chain contribution
      from Wertheim's [J. Stat. Phys. 42, 477 (1986)] TPT1 model is sufficient to
      provide quantitative accuracy for A0.

PMID- 16292935
TI  - Effect of the wall on the velocity autocorrelation function and long-time tail of
      Brownian motion in a viscous compressible fluid.
AB  - Brownian motion of a particle situated near a wall bounding the fluid in which it
      is immersed is affected by the wall. Specifically, it is assumed that a viscous
      compressible fluid fills a half space bounded by a plane wall, and that the fluid
      flow satisfies stick boundary conditions at the wall. The fluctuation-dissipation
      theorem shows that the velocity autocorrelation function of the Brownian particle
      can be calculated from the frequency-dependent admittance valid locally. The
      admittance can be found from the linearized Navier-Stokes equations. The t(-3/2)
      long-time tail of the velocity relaxation function, valid in bulk fluid, is
      obliterated by the wall and replaced by a t(-5/2) long-time tail of positive
      amplitude for motions parallel to the wall and by a t(-5/2) long-time tail of
      negative amplitude for motions perpendicular to the wall. In both cases the
      amplitude of the t(-5/2) long-time tail turns out to be independent of fluid
      compressibility and bulk viscosity.

PMID- 16292937
TI  - Proceedings of the 4th Inter-Institute Workshop on Optical Imaging from Bench to
      Bedside at the National Institutes of Health, Bethesda, Maryland, USA.

PMID- 16292936
TI  - Contrast-detail analysis characterizing diffuse optical fluorescence tomography
      image reconstruction.
AB  - Contrast-detail analysis is used to evaluate the imaging performance of diffuse
      optical fluorescence tomography (DOFT), characterizing spatial resolution limits,
      signal-to-noise limits, and the trade-off between object contrast and size.
      Reconstructed images of fluorescence yield from simulated noisy data were used to
      determine the contrast-to-noise ratio (CNR). A threshold of CNR=3 was used to
      approximate a lowest acceptable noise level in the image, as a surrogate measure
      for human detection of objects. For objects 0.5 cm inside the edge of a simulated
      tissue region, the smallest diameter that met this criteria was approximately 1.7
      mm, regardless of contrast level, and test field diameter had little impact on
      this limit. Object depth had substantial impact on object CNR, leading to a limit
      of 4 mm for objects near the center of a 51-mm test field and 8.5 mm for an 86-mm
      test field. Similarly, large objects near the edge of both test fields required a
      minimum contrast of 50% to achieve acceptable image CNR. The minimum contrast for
      large, centered objects ranged between 50% and 100%. Contrast-detail analysis
      using human detection of lower contrast limits provides fundamentally important
      information about the performance of reconstruction algorithms, and can be used
      to compare imaging performance of different systems.

PMID- 16292938
TI  - Noninvasive monitoring of red blood cell transfusion in very low birthweight
      infants using diffuse optical spectroscopy.
AB  - Red blood cell (RBC) transfusion guidelines are designed to maintain adequate
      tissue oxygenation by increasing blood oxygen-carrying capacity. However, since
      tissue oxygenation is not measured, RBC transfusion guidelines are mostly
      subjective. Clinical evidence of oxygen transport/consumption mismatches in
      infants is often unclear and confounded by multiple factors. Invasive hemoglobin
      measurements can contribute further to anemia if performed too frequently.
      Diffuse optical spectroscopy (DOS) is a noninvasive quantitative method to
      measure the tissue oxy, deoxy, and total hemoglobin concentrations (ctO2Hb, ctHb,
      ctTHb), as well as mixed arterial-venous tissue hemoglobin saturation (stO2). Our
      objective is to determine if DOS can assess changes in tissue oxygenation in very
      low birth weight (VLBW) infants undergoing RBC transfusions. DOS measurements of
      ctO2Hb and ctHb are performed on 10 VLBW infants before and within 24 h after RBC
      transfusion. Seven nontransfused infants are studied to evaluate hemodynamic
      variations independent of RBC transfusion. Tissue near-infrared absorption and
      scattering values are measured using a four-wavelength (690, 750, 810, and 830
      nm) frequency-domain tissue oximeter (OxiplexTS, ISS, Champaign, Illinois). In
      transfused subjects, DOS demonstrates significant increases in ctO2Hb (48+/-13
      versus 74+/-20 microM, p<0.002), ctTHb (87+/-17 versus 107+/-24 microM, p=0.004),
      and stO2 (54+/-8 versus 68+/-6%, p<0.004) post-transfusion. DOS measurements
      correlate with mean hemoglobin increases for all infants (r=0.83, p<0.0001). No
      significant DOS changes occurred in the nontransfused group. Calculations of the
      differential path length for these transfused subjects show high variability
      (approximately 20%). DOS may serve as a noninvasive bedside tool to assess tissue
      oxygenation in infants and provide a functionally based transfusion trigger.

PMID- 16292939
TI  - Fluorene-based fluorescent probes with high two-photon action cross-sections for
      biological multiphoton imaging applications.
AB  - Two-photon fluorescence microscopy is a powerful tool for the study of dynamic
      cellular processes and live-cell imaging. Many commercially available fluorescent
      probes have been used in multiphoton-based imaging studies despite exhibiting
      relatively low two-photon absorption cross-section values in the tunability range
      of ultrafast Ti:sapphire lasers commonly used in multiphoton microscopy imaging.
      Furthermore, available fluorophores may be plagued with low fluorescence quantum
      yield and/or photoinstability (i.e., photobleaching) on exposure to the high peak
      power and photon density provided by the ultrafast laser source. To address the
      demand for better performing dyes, we prepare fluorophores tailored for
      multiphoton imaging. These fluorophores are based on the fluorene ring system,
      known to exhibit high fluorescence quantum yield (>0.7) and high photostability.
      Furthermore, an amine-reactive fluorescent probe for the covalent attachment onto
      amine-containing biomolecules is also prepared. Epi-fluorescence and two-photon
      fluorescence microscopy images of H9c2 rat cardiomyoblasts stained with an
      efficient two-photon absorbing fluorene fluorophore is demonstrated.
      Additionally, single-photon spectral characteristics of the amine-reactive
      fluorophore, as well as the two-photon absorption cross sections of its model
      adduct in solution, and spectral characterization of a bovine serum albumin (BSA)
      as a model bioconjugate are presented.

PMID- 16292940
TI  - Toward the clinical application of time-domain fluorescence lifetime imaging.
AB  - High-speed (video-rate) fluorescence lifetime imaging (FLIM) through a flexible
      endoscope is reported based on gated optical image intensifier technology. The
      optimization and potential application of FLIM to tissue autofluorescence for
      clinical applications are discussed.

PMID- 16292941
TI  - Optical spectroscopy noninvasively monitors response of organelles to cellular
      stress.
AB  - Fast and noninvasive detection of cellular stress is extremely useful for
      fundamental research and practical applications in medicine and biology. We
      discovered that light scattering spectroscopy enables us to monitor the
      transformations in cellular organelles under thermal stress. At the temperatures
      triggering expression of heat shock proteins, the refractive index of
      mitochondria increase within 1 min after the onset of heating, indicating
      enhanced metabolic activity. At higher temperatures and longer exposures, the
      organelles increase in size. This technique provides an insight into metabolic
      processes within organelles larger than 50 nm without exogenous staining and
      opens doors for noninvasive real-time assessment of cellular stress.

PMID- 16292942
TI  - Light scattering from rat nervous system measured intraoperatively by near
      infrared reflectance spectroscopy.
AB  - Our goal is to quantify scattering properties of near-IR light in the rat spinal
      cord region and to differentiate healthy and demyelinated peripheral nerves
      intraoperatively based on differential light scattering. For the rat spinal cord,
      optical reflectance is measured from the spinal cord surface at spatial intervals
      of 1 mm using a needle probe. Data are acquired from left and right lumbar
      regions of the animals as well as on the central blood vessels. The reduced
      scattering coefficient mu(s)' is found to be higher (34.2+/-2.1 cm(-1)) in the
      lumbar regions of the spinal cord than on the central blood vessel (19.9+/-1.0
      cm(-1)). This methodology is extended to detect differences in the rat sciatic
      nerves following left L4 spinal nerve ligation. The reflectance is taken at the
      same five regions at postoperative days 1, 4, 7, and 14. Significant differences
      are seen in both the spectral slope and mu(s)' values on postoperative days 4, 7,
      and 14, indicating that either of the two quantities could be used as a marker
      for demyelination. We prove the usefulness of the technique, which may have a
      possible clinical application for minimally invasive, intraoperative diagnosis
      and monitoring of demyelination diseases, such as multiple sclerosis in the
      central nervous system or degeneration of the peripheral nervous system.

PMID- 16292944
TI  - Multiphoton fluorescence lifetime contrast in deep tissue imaging: prospects in
      redox imaging and disease diagnosis.
AB  - Turbid tissues pose serious problems of strong absorption and scattering that
      make steady state fluorescence imaging methods less successful in imaging tissue
      layers deeper than a few tens of micrometers. Complications arise as one
      progresses from imaging cells to tissues to whole animal--which include enormous
      autofluorescence background in tissues and poor signal from regions of interest.
      Since the steady state, intensity-based methods cannot discriminate the photons
      arising from the fluorophores and the autofluorescence background, it is almost
      impractical to isolate these two signals. We describe multiphoton fluorescence
      lifetime imaging methods in the time domain to demonstrate fluorescence lifetime
      contrast in discriminating autofluorescence background from the fluorescent
      signals. Since the photophysical schemes of the fluorophore and autofluorescence
      contributions are distinct, it is feasible to isolate these two contributions in
      every pixel based only on their decay constants without compromising the SNR. We
      present preliminary lifetime measurements to characterize autofluorescence in
      various cell lines and ex vivo tissues obtained from mouse models. Together,
      these results suggest a novel direction in obtaining quantitative information
      from endogenous tissue fluorescence without any exogenous staining. The prospects
      for this approach in metabolic redox imaging and disease diagnosis are discussed.

PMID- 16292943
TI  - Imaging of gene expression in living cells and tissues.
AB  - It is possible to observe gene expression within single cells using a
      tetracycline inducible promoter for activation. Transcription can be observed by
      using a fluorescent fusion protein to bind nascent RNA. Ultimately, it is
      desirable to activate a reporter gene within a single cell with only photons.
      This is achieved by preparing a chemically altered transcription factor that is
      functionally unable to activate a reporter gene until it is exposed to photon
      excitation. We apply two-photon imaging to visualize tumor cells expressing a
      transgene and ultimately this approach will provide the means to activate a
      specific gene within a single cell within any tissue to ultimately observe its
      functional significance in situ.

PMID- 16292945
TI  - Optical scattering, absorption, and polarization of healthy and neovascularized
      human retinal tissues.
AB  - The optical scattering, absorption, and polarization properties of human retinal
      tissues are investigated for a number of laser wavelengths in the visible range.
      The indices of refraction of these tissues are determined by applying Brewster's
      law. The inverse adding doubling method based on the diffusion approximation and
      radiative transport theory is applied to the measured values of total diffuse
      transmission, total diffuse reflection, and index of refraction to determine the
      optical absorption, scattering, and scattering anisotropy coefficients of the
      intact retinal tissues from healthy and diseased (neovascularized) human eyes.
      The polarization studies show that the retinal tissues possess significant
      intrinsic polarization characteristics, that are more pronounced in diseased
      tissues than in healthy tissues.

PMID- 16292946
TI  - Integrated photothermal flow cytometry in vivo.
AB  - The capability of integrated flow cytometry to detect, in real time, moving cells
      in their natural states in vivo is demonstrated in a study of circulating red and
      white blood cells in lymph and blood flow of rat mesentery. This system combines
      dual pump-probe photothermal (PT) techniques, such as PT imaging, the PT
      thermolens method, and PT velocimetry, with high-resolution (up to 0.3 microm),
      high-speed (up to 1000 fps) transmission digital microscopy (TDM) and
      fluorescence imaging. All PT techniques are based on irradiation of cells in rat
      mesenteric microvessels with a spectrally tunable laser pulse (420 to 570 nm, 8
      ns, 0.1 to 300 microJ) and on detection of temperature-dependent variations of
      the refractive index with a second continuous probe laser beam (633 nm, 1.4 mW).
      We focus on intravital monitoring of the integral PT response from single,
      moving, unlabeled cells (from 100 to 500 cells in one measurement). Potential in
      vivo applications of this new optical tool, called PT flow cytometry (PTFC), are
      discussed, including identification of selected cells with differences in natural
      absorptive properties and sizes, determination of laser-induced cell damage,
      estimation of flow velocity, and monitoring of circulating cells labeled with PT
      probes.

PMID- 16292947
TI  - Combined diffuse optical spectroscopy and contrast-enhanced magnetic resonance
      imaging for monitoring breast cancer neoadjuvant chemotherapy: a case study.
AB  - Monitoring tumor response to therapy can enable assessment of treatment efficacy,
      maximizing patient outcome and survival. We employ a noninvasive, handheld laser
      breast scanner (LBS) based on broadband diffuse optical spectroscopy (DOS) in
      conjunction with contrast-enhanced magnetic resonance imaging (cMRI) to assess
      tumor response to presurgical neoadjuvant chemotherapy. DOS and cMRI scans are
      performed after the first and fourth cycles of a doxorubicin/cyclophosphamide
      regimen in a patient with invasive ductal carcinoma. DOS measurements are used to
      quantify bulk tissue optical and physiological parameters, which are mapped to T2
      and T1-weighted cMRI images. Initial DOS measurements show high tumor/normal
      contrast in total hemoglobin concentration (THC, 56+/-7 versus 27+/-4 microM) and
      water fraction (81.4+/-1% versus 24+/-3%) colocalized with regions of strongly
      enhancing T2-weighted and cMRI signals. After the fourth cycle of chemotherapy,
      we observe decreases in peak MRI contrast-enhancement values (37.6%) and apparent
      lesion volume (21.9 versus 13.7 cm3), which corresponds to physiological changes
      measured by DOS, including a 20 to 25% reduction in the spatial extent of the
      tumor and a 38.7% drop in mean total hemoglobin content (THC, 41.6 versus 23.4
      microM). These data provide in vivo validation of the accuracy of broadband DOS
      and the sensitivity of optical methods to changes in tumor physiology.

PMID- 16292948
TI  - Combining near-infrared tomography and magnetic resonance imaging to study in
      vivo breast tissue: implementation of a Laplacian-type regularization to
      incorporate magnetic resonance structure.
AB  - An imaging system that simultaneously performs near infrared (NIR) tomography and
      magnetic resonance imaging (MRI) is used to study breast tissue phantoms and a
      healthy woman in vivo. An NIR image reconstruction that exploits the combined
      data set is presented that implements the MR structure as a soft-constraint in
      the NIR property estimation. The algorithm incorporates the MR spatially
      segmented regions into a regularization matrix that links locations with similar
      MR properties, and applies a Laplacian-type filter to minimize variation within
      each region. When prior knowledge of the structure of phantoms is used to guide
      NIR property estimation, root mean square (rms) image error decreases from 26 to
      58%. For a representative in vivo case, images of hemoglobin concentration,
      oxygen saturation, water fraction, scattering power, and scattering amplitude are
      derived and the properties of adipose and fibroglandular breast tissue types,
      identified from MRI, are quantified. Fibroglandular tissue is observed to have
      more than four times as much water content as adipose tissue, almost twice as
      much blood volume, and slightly reduced oxygen saturation. This approach is
      expected to improve recovery of abnormalities within the breast, as the inclusion
      of structural information increases the accuracy of recovery of embedded
      heterogeneities, at least in phantom studies.

PMID- 16292949
TI  - Noninvasive imaging of oral premalignancy and malignancy.
AB  - Early detection of cancer and its precursors remains the best way to ensure
      patient survival and quality of life. Our specific aim is to test a multimodality
      approach to noninvasive diagnostics of oral premalignancy and malignancy. In the
      hamster cheek pouch model (120 hamsters), in vivo optical coherence tomography
      (OCT) and optical Doppler tomography (ODT) map epithelial, subepithelial, and
      vascular change throughout carcinogenesis. In vivo multiwavelength multiphoton
      (MPM) and second-harmonic generated (SHG) fluorescence techniques provided
      parallel data on surface and subsurface tissue structure, specifically collagen
      presence and structure, cellular presence, and vasculature. Images are diagnosed
      by two blinded, prestandardized investigators using a scale from 0 to 6 for all
      modalities. After sacrifice, histopathology is evaluated on a scale of 0 to 6.
      Imaging data are reproducibly obtained with good accuracy. Carcinogenesis-related
      structural and vascular changes are clearly visible to tissue depths of 2 mm.
      Sensitivity (OCT/ODT alone, 71 to 88%; OCT+MPMSHG, 79 to 91%) and specificity
      (OCT alone, 62 to 83%; OCT+MPMSHG, 67 to 90%) compare well with conventional
      techniques. Our conclusions are that OCT/ODT and MPM/SHG are promising
      noninvasive in vivo diagnostic modalities for oral dysplasia and malignancy.

PMID- 16292950
TI  - Reflectance confocal microscopy for characterization of mammary ductal structures
      and development of neoplasia in genetically engineered mouse models of breast
      cancer.
AB  - The earliest steps of breast cancer begin with aberrations in mammary ductal
      structure. Techniques that enable an investigator to image in situ and then
      analyze the same tissue using biochemical tools facilitates identification of
      genetic networks and signaling pathways active in the imaged structure. Cellular
      confocal microscopy (VivaCell-TiBa, Rochester, New York) is used to image mammary
      ductal structures and surrounding vasculature in situ in intact wild-type and
      genetically engineered mice that develop ER alpha-initiated ductal carcinoma in
      situ (DCIS) and ER alpha-driven invasive mammary cancer. In wild-type mice,
      normal mammary ductal structures that appear from puberty through lactation are
      visualized and serially sectioned optically, and a developmental atlas is
      created. Altering tissue preparation enabled visualization of the vasculature
      surrounding the ductal structures. In the genetically engineered mice, aberrant
      mammary ductal structures and cancers are imaged and compared to corresponding
      normal structures. Different preparation techniques are able to preserve tissue
      for routine histological analyses and RNA isolation. Comparative studies
      demonstrate that reflectance confocal imaging provides more cellular detail than
      carmine-alum-stained mammary gland whole mounts and equivalent detail with
      hematoxylin and eosin stained tissue sections. In summary, reflectance confocal
      microscopy is a tool that can be used to rapidly and accurately analyze mammary
      gland structure.

PMID- 16292952
TI  - Prospective grading of neoplastic change in rat esophagus epithelium using angle
      resolved low-coherence interferometry.
AB  - Angle-resolved low-coherence interferometry (a/LCI) is used to obtain
      quantitative, depth-resolved nuclear morphology measurements. We compare the
      average diameter and texture of cell nuclei in rat esophagus epithelial tissue to
      grading criteria established in a previous a/LCI study to prospectively grade
      neoplastic progression. We exploit the depth resolution of a/LCI to exclusively
      examine the basal layer of the epithelium, approximately 50 to 100 microm beneath
      the tissue surface, without the need for exogenous contrast agents, tissue
      sectioning, or fixation. The results of two studies are presented that compare
      the performance of two a/LCI modalities. Overall, the combined studies show 91%
      sensitivity and 97% specificity for detecting dysplasia, using histopathology as
      the standard. In addition, the studies enable the effects of dietary
      chemopreventive agents, difluoromethylornithine (DFMO) and curcumin, to be
      assessed by observing modulation in the incidence of neoplastic change. We
      demonstrate that a/LCI is highly effective for monitoring neoplastic change and
      can be applied to assessing the efficacy of chemopreventive agents in the rat
      esophagus.

PMID- 16292951
TI  - Optical coherence tomography in the diagnosis and treatment of neurological
      disorders.
AB  - Optical contrast is often the limiting factor in the imaging of live biological
      tissue. Studies were conducted in postmortem human brain to identify clinical
      applications where the structures of interest possess high intrinsic optical
      contrast and where the real-time, high-resolution imaging capabilities of optical
      coherence tomography (OCT) may be critical. Myelinated fiber tracts and blood
      vessels are two structures with high optical contrast. The ability to image these
      two structures in real time may improve the efficacy and safety of a
      neurosurgical procedure to treat Parkinson's disease called deep brain
      stimulation (DBS). OCT was evaluated as a potential optical guidance system for
      DBS in 25 human brains. The results suggest that catheter-based OCT has the
      resolution and contrast necessary for DBS targeting. The results also demonstrate
      the ability of OCT to detect blood vessels with high sensitivity, suggesting a
      possible means to avoid their laceration during DBS. Other microscopic structures
      in the human brain with high optical contrast are pathological vacuoles
      associated with transmissible spongiform encephalopathy (TSE). TSE include
      diseases such as Mad Cow disease and Creutzfeldt-Jakob disease (CJD) in humans.
      OCT performed on the brain from a woman who died of CJD was able to detect
      clearly the pathological vacuoles.

PMID- 16292953
TI  - Image quality improvement via spatial deconvolution in optical tomography: time
      series imaging.
AB  - We present the fourth in a series of studies devoted to the issue of improving
      image quality in diffuse optical tomography (DOT) by using a spatial
      deconvolution operation that seeks to compensate for the information-blurring
      property of first-order perturbation algorithms. Our earlier reports consider
      only static target media. Here we report spatial deconvolution applied to media
      with time-varying optical properties, as a model of tissue dynamics resulting
      from varying metabolic demand and modulation of the vascular bed. Issues under
      study include the influence of deconvolution on the accuracy of the recovered
      temporal and spatial information. The impact of noise is also explored, and
      techniques for ameliorating its information-degrading effects are examined. At
      low noise levels (i.e, < or = 5% of the time-varying signal amplitude), spatial
      deconvolution markedly improves the accuracy of recovered information. Temporal
      information is more seriously degraded by noise than is spatial information, and
      the impact of noise increases with the complexity of the time-varying signal.
      These effects, however, can be significantly reduced using simple noise
      suppression techniques (e.g., low-pass filtering). Results suggest that the
      deconvolution scheme should provide considerable enhancement of the quality of
      spatiotemporal information recovered from dynamic DOT techniques applied to
      tissue studies.

PMID- 16292954
TI  - Image analysis of bioparticles accumulation and diamagnetic alignment in high
      gradient magnetic field.
AB  - Magnetic properties of biological particles are measured in high-gradient
      magnetic separation (HGMS) analysis, revealing the concentrating process of
      nucleoprotein particles, ferritin, red blood cells, and eggs. A magnetic force
      acting on micrometer and submicrometer biological particles having diamagnetic or
      paramagnetic susceptibility with respect to the solution causes their movement
      and accumulation in gradient magnetic fields dependent on the values of the
      magnetic moments. The methods developed enable us to obtain the magnetic moments
      values of single particles and their assembly directly from magnetic separation
      and image analyses without assuming the detection of sizes. Our precision methods
      for the measurement of the capture traveling (magnetic diffusion) time and the
      accumulation (magnetic sedimentation) radius in HGMS show that it is really
      possible to determine the weak dia- or paramagnetic shifts of magnetic
      susceptibility up to 0.7x10(-10) (SI units). HGMS analysis of the concentrating
      process of nucleoprotein granules (microcells, DNA granules, or nucleosome core
      particles) with polarization microscopy reveals phase transitions for DNA in
      granules, and separation accumulation of particles enables the determination of
      the diamagnetic susceptibility and anisotropy properties. Magnetic concentration
      effects always occur in living systems because micrometer-located gradient
      magnetic fields inside an organism are strong enough to cause drifts of cellular
      complexes and organelles of micrometer and submicrometer sizes. We report the
      appearance of superparamagnetic contamination inside developing shrimp eggs. In
      the developing shrimps eggs, ferritin aggregates are observed under weak gradient
      magnetic fields and diaparaferromagnetic changes are detected. A significant
      interruption of egg development is revealed in such fields.

PMID- 16292955
TI  - Macro-optical color assessment of the pulmonary airways with subsequent three
      dimensional multidetector-x-ray-computed-tomography assisted display.
AB  - Bronchial diseases alter the color and structural characteristics of the
      pulmonary mucosa through changes in blood flow, epithelial thickening, and
      abnormal cell growth. Current analysis of these subtle changes includes visual
      interpretation of the airway color and topography through bronchoscopy
      procedures, and quantitative multidetector-x-ray-computed-tomography (MDCT)-based
      structural analysis, each affording valuable insights to the health of the lungs.
      The fusion of the bronchoscopy and MDCT image data promises to provide a
      synergistic data set exhibiting both mucosal color and topography crucial to
      fostering an understanding of airway structure and function. A real-time airway
      color analysis imaging system is developed and utilized to perform pulmonary
      mucosal color assessment in healthy volunteers with subsequent comparative
      studies performed in example disease states. Our results indicate that macro
      optical digital bronchoscopes with appropriate image analysis may have a
      significant impact on understanding bronchial diseases. To ensure the correct
      interpretation of scene content, which is critical in the assessment of airway
      topography, we are developing methods of extracting 3-D structure from 2-D
      bronchoscope images utilizing MDCT imaging techniques. The resulting 3-D true
      color images of the pulmonary mucosa facilitate the combination of mucosal color
      and topography analysis as well as region of interest localization within the
      airway tree.

PMID- 16292956
TI  - Approximation of Mie scattering parameters in near-infrared tomography of normal
      breast tissue in vivo.
AB  - A method for estimating Mie theory scattering parameters from diffuse light
      tomography measurements in breast tissue is discussed. The approach provides an
      estimate of the mean particle size and number density given assumptions about the
      index of refraction change expected in lipid-membrane-bound scatterers. When
      using a sparse number of wavelengths in the reduced scattering spectra, the
      parameter extraction technique is limited to representing a continuous
      distribution of scatterer sizes that appears to be dominated by an exponential
      decrease with increasing particle size. The fitting method is tested on simulated
      data and then on Intralipid-based tissue-phantom data, giving a mean particle
      size of 93+/-17 nm, which is in excellent agreement with expectations. The
      approach is also applied retrospectively to breast tissue spectra acquired from
      normal healthy volunteers, where the average particle size and number density
      were found to be in the range of 20 to 1400 nm. Grouping of the data based on
      radiographic breast density, as a surrogate measure of tissue composition yielded
      values of 20 to 65, 25 to 200, 140 to 1200, and 150 to 1400 nm, respectively, for
      the four BI-RADS (American College of Radiology Breast Imaging Reporting and Data
      System) density classifications of extremely dense, heterogeneously dense,
      scattered, and fatty. These results are consistent with the microscopic
      characteristics of each breast type given the expected progression from
      predominantly collagenous connective tissue (extremely dense category) to
      increasing proportions of glandular epithelium and fat (intermediate density
      categories) to predominantly fat (fatty category).

PMID- 16292957
TI  - Optical imaging of turbid media using independent component analysis: theory and
      simulation.
AB  - A new imaging approach for 3-D localization and characterization of objects in a
      turbid medium using independent component analysis (ICA) from information theory
      is developed and demonstrated using simulated data. This approach uses a
      multisource and multidetector signal acquisition scheme. ICA of the perturbations
      in the spatial intensity distribution measured on the medium boundary sorts out
      the embedded objects. The locations and optical characteristics of the embedded
      objects are obtained from a Green's function analysis based on any appropriate
      model for light propagation in the background medium. This approach is shown to
      locate and characterize absorptive and scattering inhomogeneities within highly
      scattering medium to a high degree of accuracy. In particular, we show this
      approach can discriminate between absorptive and scattering inhomogeneities, and
      can locate and characterize complex inhomogeneities, which are both absorptive
      and scattering. The influence of noise and uncertainty in background absorption
      or scattering on the performance of this approach is investigated.

PMID- 16292958
TI  - Enhancement of hidden structures of early skin fibrosis using polarization degree
      patterns and Pearson correlation analysis.
AB  - The skin of athymic nude mice is irradiated with a single dose of x-ray
      irradiation that initiated fibrosis. Digital photographs of the irradiated mice
      are taken by illuminating the mouse skin with linearly polarized probe light of
      650 nm. The specific pattern of the surface distribution of the degree of
      polarization enables the detection of initial skin fibrosis structures that were
      not visually apparent. Data processing of the raw spatial distributions of the
      degree of polarization based on Fourier filtering of the high-frequency noise
      improves subjective perception of the revealed structure in the images. In
      addition, Pearson correlation analysis provides information about skin structural
      size and directionality.

PMID- 16292959
TI  - Two-dimensional phased arrays of sources and detectors for depth discrimination
      in diffuse optical imaging.
AB  - We present a multisource, multidetector phased-array approach to diffuse optical
      imaging that is based on postprocessing continuous-wave data. We previously
      showed that this approach enhances the spatial resolution of diffuse optical
      imaging. We now demonstrate the depth discrimination capabilities of this
      approach and its potential to perform tomographic sectioning of turbid media. The
      depth discrimination results from the dependence of the sensitivity function on
      the depth coordinate z. To demonstrate the potential of this approach, we perform
      an experimental study of a turbid medium containing cylindrical inhomogeneities
      that are placed 2.0, 3.0, and 4.0 cm from a seven-element, 2-D source array. A
      single detector element is placed at a distance of 6.0 cm from the source array,
      and the measurement is repeated after switching the positions of the detector and
      the source array to simulate the case where both sources and detectors consist of
      a 2-D array of elements. We find that the proposed phased-array method is able to
      separate cylinders at different depths, thus showing cross-sectioning
      capabilities.

PMID- 16292960
TI  - Acousto-optic-tunable-filter-based spectropolarimetric imagers for medical
      diagnostic applications--instrument design point of view.
AB  - Compact optical imagers that can detect both spectral and polarization signatures
      are required in many biomedical applications. An acousto-optic-tunable-filter
      (AOTF)-based imager is ideally suited to provide both agile spectral and
      polarization signatures. Such an imager can be readily used for real-time in vivo
      medical diagnostic applications. We develop a family of small, robust, and
      programmable hyperspectral imagers operating from the ultraviolet (UV) to the
      long-wave IR (LWIR). Such imagers require minimal data processing because they
      can acquire images at only select wavelengths of interest. We use AOTFs made of
      KDP, TeO2, and TAS with Si-based CCD, InGaAs, InSb, and HgCdTe cameras to cover
      different spectral regions from the UV to the LWIR. Operation of each of these
      imagers and image acquisition is computer controlled. The most developed imager
      covers the visible to near-infrared (VNIR) region from 400 to 900 nm, with a 10
      nm spectral resolution at 600 nm, it uses an electronically tunable TeO2 AOTF as
      a bandpass filter, and a nematic liquid crystal retarder to change polarization.
      We describe our concept in the development of these imagers and present new
      results obtained using the VNIR imager.

PMID- 16292961
TI  - Four-dimensional cardiac imaging in living embryos via postacquisition
      synchronization of nongated slice sequences.
AB  - Being able to acquire, visualize, and analyze 3D time series (4D data) from
      living embryos makes it possible to understand complex dynamic movements at early
      stages of embryonic development. Despite recent technological breakthroughs in 2D
      dynamic imaging, confocal microscopes remain quite slow at capturing optical
      sections at successive depths. However, when the studied motion is periodic--such
      as for a beating heart--a way to circumvent this problem is to acquire,
      successively, sets of 2D+time slice sequences at increasing depths over at least
      one time period and later rearrange them to recover a 3D+time sequence. In other
      imaging modalities at macroscopic scales, external gating signals, e.g., an
      electro-cardiogram, have been used to achieve proper synchronization. Since
      gating signals are either unavailable or cumbersome to acquire in microscopic
      organisms, we have developed a procedure to reconstruct volumes based solely on
      the information contained in the image sequences. The central part of the
      algorithm is a least-squares minimization of an objective criterion that depends
      on the similarity between the data from neighboring depths. Owing to a wavelet
      based multiresolution approach, our method is robust to common confocal
      microscopy artifacts. We validate the procedure on both simulated data and in
      vivo measurements from living zebrafish embryos.

PMID- 16292962
TI  - Resonance Raman spectroscopic measurement of carotenoids in the skin and retina.
AB  - Carotenoid pigments within the skin and retina are measured using resonance Raman
      spectroscopy (RS). These RS instruments are unique in that they have been
      designed to obtain vibrational spectra in normal and diseased subjects using
      noninvasive procedures. Raman spectra have traditionally been used as a means of
      identifying a given chemical within some substrate. The new generation of RS
      instruments, however, has been designed to quantify the amount of carotenoids
      within the retina and skin. These amounts are typically reported in
      nonstandardized units called Raman counts (RC). These RCs are dependent on many
      factors intrinsic to their measurement, such as the specific optics used for
      stimulation and acquisition. The question of whether RCs can be used to derive
      valid quantitative measures of the carotenoid pigments in vivo is discussed.

PMID- 16292963
TI  - Whole-body fluorescence lifetime imaging of a tumor-targeted near-infrared
      molecular probe in mice.
AB  - Fluorescence lifetime imaging can provide valuable diagnostic information
      relating to the functional status of diseases. In this study, a near-infrared
      (NIR) dye-labeled hexapeptide (abbreviated Cyp-GRD) was synthesized. In vitro,
      Cyp-GRD internalized in nonsmall cell lung cancer cells (A549) without observable
      cytotoxic or proliferative effects to the cells at a concentration up to 1x10(-4)
      M. Time-domain fluorescence intensity and lifetime imaging of Cyp-GRD injected
      into A549 tumor-bearing mice revealed that the probe preferentially accumulated
      in the tumor and the major excretion organs. The fluorescence lifetime of the
      conjugate at the tumor site was mapped, showing the spatial distribution of the
      lifetime related to its environment. Additionally, fluorescence intensity image
      reconstruction obtained by integrating the time-resolved intensities enabled the
      contrast ratios of tumor-to-kidney or liver in slices at different depths to be
      displayed. The mean lifetime was 1.03 ns for the tumor and 0.80 ns for the liver
      when averaging those pixels exhibiting adequate signal-to-noise ratio, showing
      the tumor had a higher lifetime average and reflecting the altered
      physiopathology of the tumor. This study clearly demonstrated the feasibility of
      whole-body NIR fluorescence lifetime imaging for tumor localization and its
      spatial functional status in living small animals.

PMID- 16292964
TI  - Determination of visible near-IR absorption coefficients of mammalian fat using
      time- and spatially resolved diffuse reflectance and transmission spectroscopy.
AB  - In-vivo optical spectroscopy and the determination of tissue absorption and
      scattering properties have a central role in the development of novel optical
      diagnostic and therapeutic modalities in medicine. A number of techniques are
      available for the optical characterization of tissue in the visible near-IR
      region of the spectrum. An important consideration for many of these techniques
      is the reliability of the absorption spectrum of the various constituents of
      tissue. The availability of accurate absorption spectra in the range 600 to 1100
      nm may allow for the determination of the concentration of key tissue
      constituents such as oxy- and deoxy-hemoglobin, water, and lipids. The objective
      of the current study is the determination of a reliable absorption spectrum of
      lipid(s) that can be used for component analysis of in-vivo spectra. We report
      the absorption spectrum of a clear purified oil obtained from pig lard. In the
      liquid phase above 36 degrees C, the oil is transparent and thus suitable for
      collimated transmission measurements. At room temperature, the oil is a solid
      grease that is highly scattering. The absorption and scattering properties in
      this solid phase are measured using time- and spatially resolved diffuse
      reflectance spectroscopy. Using these three independent measurement techniques,
      we have determined an accurate estimate for the absorption spectrum of mammalian
      fat.

PMID- 16292965
TI  - Optical sensor based on fluorescent quenching and pulsed blue LED excitation for
      long-term monitoring of dissolved oxygen in NASA space bioreactors.
AB  - There is a need to monitor the concentration of dissolved oxygen (DO) present in
      the culture medium for NASA's space cell biology experiments, as well as in earth
      based cell cultures. Continuous measurement of DO concentration in the cell
      culture medium in perfused bioreactors requires that the oxygen sensor provide
      adequate sensitivity and low toxicity to the cells, as well as maintain
      calibration over several weeks. Although there are a number of sensors for
      dissolved oxygen on the market and under development elsewhere, very few meet
      these stringent conditions. An in-house optical oxygen sensor (HOXY) based on
      dynamic fluorescent quenching of Tris(4,7-diphenyl-1,10
      phenanthroline)ruthenium(II) chloride and a pulsed blue LED light source was
      developed in our laboratory to address these requirements. The sensing element
      consisted of the fluorescent dye embedded in a silicone matrix and coated onto a
      glass capillary. Photobleaching was minimized by a pulsed LED light source. The
      total noise in the sensor output is 2% and the sensor dynamic range is 0 to 200
      mm Hg. The resolution of the sensor is 0.1 mm Hg at 50 mm Hg, and 0.25 mm Hg at
      130 mm Hg, while the accuracy is 5%. The LED-based oxygen sensor exhibited stable
      performance and low drift, making it compatible for space-flight bioreactor
      systems.

PMID- 16292966
TI  - Compact fiber-delivered Cr:forsterite laser for nonlinear light microscopy.
AB  - We demonstrate a compact and self-starting fiber-delivered femtosecond
      Cr:forsterite laser for nonlinear light microscopy. A semiconductor saturable
      absorber mirror provides the self-starting mechanism and maintains long-term
      stability in the laser cavity. Four double-chirped mirrors are employed to reduce
      the size of the cavity and to compensate for group velocity dispersion. Delivered
      by a large-mode-area photonic crystal fiber, the generated laser pulses can be
      compressed down to be with a nearly transform-limited pulse width with 2.2-nJ
      fiber-output pulse energy. Based on this fiber-delivered Cr:forsterite laser
      source, a compact and reliable two-photon fluorescence microscopy system can thus
      be realized.

PMID- 16292967
TI  - Fluorescence emission patterns near glass and metal-coated surfaces investigated
      with back focal plane imaging.
AB  - Often fluorophores observed by microscopy are located close to a planar surface
      as in total internal reflection microscopy or single molecule studies. The
      optical properties of fluorescence excitation and emission near a planar surface
      (possibly metal film coated) between two dielectrics are well understood from the
      viewpoint of classical electromagnetic theory. We present an experimental method
      whereby the angular dependence of the emission pattern of a fluorophore near a
      bare surface or a metal film coated surface that supports surface plasmon
      resonance can be measured with microscope optics. The technique involves an
      alteration of the microscope optics to directly record (on a digital CCD camera)
      the intensity pattern at the objective's back focal plane, which directly maps
      the angular emission pattern of fluorescence. The experimental emission profile
      on both glass and aluminum-coated surfaces is anisotropic with a peak at either
      the critical angle or both the critical angle and the surface plasmon angle. The
      observed profiles agree well with computer calculations and suggest some optical
      modifications that are potentially useful in cell biophysics.

PMID- 16292968
TI  - Parallel dual-color fluorescence cross-correlation spectroscopy using diffractive
      optical elements.
AB  - Dual-color cross-correlation spectroscopy allows the detection and quantification
      of labeled biomolecules at ultra-low concentrations, whereby the sensitivity of
      the assay correlates with the measurement time. We now describe a parallel
      multifocal dual-color spectroscopic configuration employing multiple avalanche
      photodiodes and hardware correlators. Cross-correlation curves are obtained from
      several dual-color excitation foci simultaneously. Multifocal dual-color
      excitation is achieved by splitting each of two laser beams (488 and 633 nm) into
      four sub-beams with the help of two 2x2 fan-out diffractive optical elements
      (DOEs), and subsequent superposition of the two sets of four foci. The
      fluorescence emission from double-labeled biomolecules is detected by two 2x2
      fiber arrays.

PMID- 16292969
TI  - Excitation beyond the monochromatic laser limit: simultaneous 3-D confocal and
      multiphoton microscopy with a tapered fiber as white-light laser source.
AB  - Confocal and multiphoton microscopy are essential tools in modern life sciences.
      They allow fast and highly resolved imaging of a steadily growing number of
      fluorescent markers, ranging from fluorescent proteins to quantum dots and other
      fluorophores, used for the localization of molecules and the quantitative
      detection of molecular properties within living cells and organisms. Up to now,
      only one physical limitation seemed to be unavoidable. Both confocal and
      multiphoton microscopy rely on lasers as excitation sources, and their
      monochromatic radiation allows only a limited number of simultaneously usable
      dyes, which depends on the specific number of laser lines available in the used
      microscope. We have overcome this limitation by successfully replacing all
      excitation lasers in a standard confocal microscope with pulsed white light
      ranging from 430 to 1300 nm generated in a tapered silica fiber. With this easily
      reproducible method, simultaneous confocal and multiphoton microscopy was
      demonstrated. By developing a coherent and intense laser source with spectral
      width comparable to a mercury lamp, we provide the flexibility to excite any
      desired fluorophore combination.

PMID- 16292970
TI  - Quality analysis of in vivo near-infrared fluorescence and conventional gamma
      images acquired using a dual-labeled tumor-targeting probe.
AB  - The cyclic peptide, cyclopentapeptide cyclo(lys-Arg-Gly-Asp-phe) (c(KRGDf)),
      which is known to target alpha(v)beta3 integrin, is dual-labeled with a
      radiotracer, (111)indium, for gamma scintigraphy as well as with a near-infrared
      dye, IRDye800, for continuous-wave (cw) imaging of alpha(v)beta3 positive human
      M21 melanoma in xenografts. Twenty-four hours after administration of the dual
      labeled peptide at a dose equivalent to 90 microCi of (111)In and 5 nmol of near
      infrared (NIR) dye, whole-body gamma scintigraphy and cw imaging was conducted.
      Image acquisition time was 15 min for the gamma scintigraphy images and 800 ms
      for the optical images acquired using an NIR sensitive intensified charge-coupled
      device. The results show that while the target-to-background ratio (TBR) of
      nuclear and optical imaging were similar for surface regions of interest and
      consistent with the origin of gamma and NIR radiation from a common targeted
      peptide, the signal-to-noise ratio (SNR) was significantly higher for optical
      than nuclear imaging. Furthermore, an analysis of SNR versus contrast showed
      greater sensitivity of optical over nuclear imaging for the subcutaneous tumor
      targets. While tomographic reconstructions are necessary to probe TBR, SNR, and
      contrast for interior tissues, this work demonstrates for the first time the
      direct comparison of molecular optical and planar nuclear imaging for surface and
      subsurface cancers.

PMID- 16292972
TI  - Wavelet-based characterization of spectral fluctuations in normal, benign, and
      cancerous human breast tissues.
AB  - Fluorescence intensity fluctuations in the visible wavelength regime in normal,
      benign, and cancerous human breast tissue samples are studied through wavelet
      transform. The analyses have been carried out in unpolarized, parallel and
      perpendicularly polarized channels, for optimal tissue characterization. It has
      been observed that polarized fluorescence data, particularly the perpendicular
      components, differentiate various tissue types quite well. Wavelet transform,
      because of its ability for multiresolution analysis, provides the ideal tool to
      separate and characterize fluctuations in the fluorescence spectra at different
      scales. We quantify these differences and find that the fluctuations in the
      perpendicular channel of the cancerous tissues are more randomized as compared to
      their normal counterparts. Furthermore, for cancerous tissues, the same is very
      well described by the normal distribution, which is not the case for normal and
      benign samples. It has also been observed that, up to a certain point,
      fluctuations at larger scales are more sensitive to tissue types. The differences
      in the average, low-pass wavelet coefficients of normal, cancerous,
      pericanalicular, and intracanalicular benign tissues are also pointed out.

PMID- 16292971
TI  - Time-resolved optical mammography using a liquid coupled interface.
AB  - A method has been devised for generating three-dimensional optical images of the
      breast using a 32-channel time-resolved system and a liquid-coupled interface.
      The breast is placed in a hemispherical cup surrounded by sources and detectors,
      and the remaining space is filled with a fluid with tissue-like optical
      properties. This approach has three significant benefits. First, cups can
      accommodate a large range of breast sizes, enabling the entire volume of the
      breast to be sampled. Second, the coupling of the source and detector optics at
      the surface is constant and independent of the subject, enabling intensity
      measurements to be employed in the image reconstruction. Third, the external
      geometry of the reconstructed volume is known exactly. Images of isolated targets
      with contrasting absorbing and scattering properties have been acquired, and the
      performance of the system has been evaluated in terms of the contrast, spatial
      resolution, and localization accuracy. These parameters were strongly dependent
      on the location of the targets within the imaged volume. Preliminary images of a
      healthy human subject are also presented, which reveal subtle heterogeneity,
      particularly in the distribution of scatter. The ability to detect an absorbing
      target adjacent to the breast is also demonstrated.

PMID- 16292974
TI  - Polarimetric imaging of subsurface tissue-numerical results.
AB  - Tissue images obtained at deeper depths lack significant contrast. To enhance the
      contrast of these images and to increase the visibility of subsurface tissues, a
      method is proposed. This technique is based on the principle that photons at
      longer wavelengths penetrate deeper than photons at shorter wavelengths. In this
      technique, images in the original and orthogonal polarized states are recorded
      with the source illumination in linear polarized state at two different
      wavelengths. Image subtraction of a fraction of the copolarized image from the
      perpendicular polarized state is done on these images. The images obtained after
      the first processing are subjected to the next image subtraction where the
      shorter wavelength image is subtracted from the longer wavelength image. Monte
      Carlo simulations show that the resultant image has marked contrast up to 2.5 cm.

PMID- 16292973
TI  - Algorithms for automated oximetry along the retinal vascular tree from dual
      wavelength fundus images.
AB  - We present an automated method to perform accurate, rapid, and objective
      measurement of the blood oxygen saturation over each segment of the retinal
      vascular hierarchy from dual-wavelength fundus images. Its speed and automation
      (2 s per entire image versus 20 s per segment for manual methods) enables
      detailed level-by-level measurements over wider areas. An automated tracing
      algorithm is used to estimate vessel centerlines, thickness, directions, and
      locations of landmarks such as bifurcations and crossover points. The
      hierarchical structure of the vascular network is recovered from the trace
      fragments and landmarks by a novel algorithm. Optical densities (OD) are measured
      from vascular segments using the minimum reflected intensities inside and outside
      the vessel. The OD ratio (ODR=OD600/OD570) bears an inverse relationship to
      systemic HbO2 saturation (SO2). The sensitivity for detecting saturation change
      when breathing air versus pure oxygen was calculated from the measurements made
      on six subjects and was found to be 0.0226 ODR units, which is in good agreement
      with previous manual measurements by the dual-wavelength technique, indicating
      the validity of the automation. A fully automated system for retinal vessel
      oximetry would prove useful to achieve early assessments of risk for progression
      of disease conditions associated with oxygen utilization.

PMID- 16292975
TI  - Optical investigations to avoid the disturbing influences of furrows and wrinkles
      quantifying penetration of drugs and cosmetics into the skin by tape stripping.
AB  - Furrows and wrinkles, as typical structures of human skin, represent a reservoir
      for topically applied substances. This reservoir can influence penetration
      experiments of topically applied substances into the stratum corneum by tape
      stripping. Optical methods such as laser-scanning microscopy, optical coherent
      tomography, and the microscopical investigation of histological sections obtained
      by biopsies were used to check a special protocol, which avoids these potential
      disturbances. The use of a transparent adhesive film with high flexibility and
      the realization of an intense contact to the stretched skin by pressing the tape
      with a roll, moved laterally on the tape, are the prerequisites to obtain correct
      data. The application of this experimental technique and the performance of tape
      stripping allow the determination of the horny layer profile and the local
      distribution of topically applied substance, undisturbed by the characteristic
      structure of the natural skin. These results demonstrate that the presented tape
      stripping procedure is a valuable tool to determine, quantitatively, the
      penetration and the bioavailability of drugs and cosmetics inside the human
      stratum corneum, in relation to the horny layer profile.

PMID- 16292977
TI  - Can Fourier transform infrared spectroscopy at higher wavenumbers (mid IR) shed
      light on biomarkers for carcinogenesis in tissues?
AB  - Fourier transform infrared microspectroscopy (FTIR-MSP) has shown promise as a
      technique for detection of abnormal cell proliferation and premalignant
      conditions. In the present study, we investigate the absorbance in the sensitive
      wavenumber region between 2800 and 3000 cm(-1), which has been known to be due to
      the antisymmetric and symmetric stretching vibrations of CH2 and CH3 groups of
      proteins and lipids. We report common biomarkers from this region that
      distinguish between normal and malignant tissues and cell lines. Based on our
      findings, we propose that the wavenumber region around 2800 to 3000 cm(-1) in the
      FTIR spectra of cells and tissues could provide valuable scientific evidence at
      the onset of premalignancy and may be used for ex vivo and in vitro detection of
      carcinogenesis. To further examine the utility of these markers in cancer
      diagnosis and management, they are tested successfully in monitoring the changes
      occurring in leukemia patients during chemotherapy.

PMID- 16292976
TI  - Near-infrared fiber optic spectroscopy as a novel diagnostic tool for the
      detection of pancreatic cancer.
AB  - We have investigated the application of near-infrared (NIR) fiber-optic
      spectroscopy for the diagnosis of pancreatic cancer. Cluster analysis of the
      Fourier transformed near-infrared (FTNIR) fiber-optic spectra of surgically
      resected pancreatic tumor tissues allowed discrimination of tumor from normal
      tissue with high sensitivity and specificity. The sensitivity of the method using
      spectral information of the CH stretching first overtone region (5951-5608 cm(
      1)) was 83.3% with a specificity of 83.3%. Based on the CH stretching second
      overtone region (8605-7938 cm(-1)) we could achieve a sensitivity of 88.9% and
      specificity of 72.2%. These findings suggest that NIR spectroscopy offers the
      potential for minimally invasive in-vivo diagnosis of pancreatic cancer.

PMID- 16292978
TI  - In vivo integrated flow image cytometry and lymph/blood vessels dynamic
      microscopy.
AB  - The high spatial resolution (approximately 350 nm) transmission digital
      microscopy (TDM) was developed for real time in vivo imaging of microlymphatics
      of rat mesentery at a single cell level without any contrast agent. The main
      mesenteric microstructures (lymph-vessel diameter, valve geometry, cells, etc.)
      and their dynamics (wall motion, valve function, cell velocity, etc.) were
      monitored with TDM. Depending on structure size, different magnifications were
      used to image relatively large whole lymphangion (x4 to x10) as well as to image
      single cells (x40 to x100) in lymph and blood flow including estimation of their
      shape, size, and aggregation state. Various potential applications of the TDM for
      in vivo studies are discussed, including visualization of circulating cells in
      lymph and blood flows, studying the kinetics of platelets, leukocyte rolling, as
      well as imaging absorbing nonfluorescent mesentery structures and leukocytes with
      a high optical resolution.

PMID- 16292979
TI  - Characterizing the thermally induced structural changes to intact porcine eye,
      part 1: second harmonic generation imaging of cornea stroma.
AB  - We characterize the structural changes of porcine corneal structures from 25 to
      90 degrees C using second harmonic generation (SHG) microscopy. Our results show
      that porcine stroma undergoes several distinct stages of structural changes
      between 25 and 90 degrees C. A decrease in SHG intensity from 30 to 45 degrees C
      and the existence of SHG intensity peaks at 53, 65, and 77 degrees C correlate to
      distinct structural alterations of the corneal stroma. At higher temperatures,
      the SHG intensity decreases and a baseline in SHG signal is reached at 90 degrees
      C. Our results demonstrate that SHG microscopy is a useful technique for
      obtaining qualitative and quantitative information of thermally treated corneal
      fibers without histological or labeling procedures. With additional developments,
      SHG imaging may be developed into an effective imaging technique for in vivo
      characterization of cornea structural changes.

PMID- 16292981
TI  - Tracing the origin and spread of agriculture in Europe.
AB  - The origins of early farming and its spread to Europe have been the subject of
      major interest for some time. The main controversy today is over the nature of
      the Neolithic transition in Europe: the extent to which the spread was, for the
      most part, indigenous and animated by imitation (cultural diffusion) or else was
      driven by an influx of dispersing populations (demic diffusion). We analyze the
      spatiotemporal dynamics of the transition using radiocarbon dates from 735 early
      Neolithic sites in Europe, the Near East, and Anatolia. We compute great-circle
      and shortest-path distances from each site to 35 possible agricultural centers of
      origin--ten are based on early sites in the Middle East and 25 are hypothetical
      locations set at 5 degrees latitude/longitude intervals. We perform a linear fit
      of distance versus age (and vice versa) for each center. For certain centers,
      high correlation coefficients (R > 0.8) are obtained. This implies that a steady
      rate or speed is a good overall approximation for this historical development.
      The average rate of the Neolithic spread over Europe is 0.6-1.3 km/y (95%
      confidence interval). This is consistent with the prediction of demic diffusion
      (0.6-1.1 km/y). An interpolative map of correlation coefficients, obtained by
      using shortest-path distances, shows that the origins of agriculture were most
      likely to have occurred in the northern Levantine/Mesopotamian area.

PMID- 16292982
TI  - Securin is not required for chromosomal stability in human cells.
AB  - Abnormalities of chromosome number are frequently observed in cancers. The
      mechanisms regulating chromosome segregation in human cells are therefore of
      great interest. Recently it has been reported that human cells without an
      hSecurin gene lose chromosomes at a high frequency. Here we show that, after
      hSecurin knockout through homologous recombination, chromosome losses are only a
      short, transient effect. After a few passages hSecurin(-/-) cells became
      chromosomally stable and executed mitoses normally. This was unexpected, as the
      securin loss resulted in a persisting reduction of the sister-separating protease
      separase and inefficient cleavage of the cohesin subunit Scc1. Our data
      demonstrate that securin is dispensable for chromosomal stability in human cells.
      We propose that human cells possess efficient mechanisms to compensate for the
      loss of genes involved in chromosome segregation.

PMID- 16292986
TI  - Evolving role of clopidogrel in acute coronary syndromes.

PMID- 16292988
TI  - Gene expression and heart failure. 24-27 July 2005, 2nd Annual Symposium of the
      American Heart Association Council on Basic Cardiovascular Sciences, Keystone,
      CO, USA.

PMID- 16292983
TI  - Ankyrin-B coordinates the Na/K ATPase, Na/Ca exchanger, and InsP3 receptor in a
      cardiac T-tubule/SR microdomain.
AB  - We report identification of an ankyrin-B-based macromolecular complex of Na/K
      ATPase (alpha 1 and alpha 2 isoforms), Na/Ca exchanger 1, and InsP3 receptor that
      is localized in cardiomyocyte T-tubules in discrete microdomains distinct from
      classic dihydropyridine receptor/ryanodine receptor "dyads." E1425G mutation of
      ankyrin-B, which causes human cardiac arrhythmia, also blocks binding of ankyrin
      B to all three components of the complex. The ankyrin-B complex is markedly
      reduced in adult ankyrin-B(+/-) cardiomyocytes, which may explain elevated
      [Ca2+]i transients in these cells. Thus, loss of the ankyrin-B complex provides a
      molecular basis for cardiac arrhythmia in humans and mice. T-tubule-associated
      ankyrin-B, Na/Ca exchanger, and Na/K ATPase are not present in skeletal muscle,
      where ankyrin-B is expressed at 10-fold lower levels than in heart. Ankyrin-B
      also is not abundantly expressed in smooth muscle. We propose that the ankyrin-B
      based complex is a specialized adaptation of cardiomyocytes with a role for
      cytosolic Ca2+ modulation.

PMID- 16292989
TI  - Sitaxsentan: a novel endothelin-A receptor antagonist for pulmonary arterial
      hypertension.
AB  - Sitaxsentan is an orally active, selective endothelin-A receptor antagonist that
      may benefit patients with pulmonary arterial hypertension by blocking the
      vasoconstrictive effects of endothelin-A receptors, while maintaining the
      vasodilator and endothelin-1 clearance functions of the endothelin-B receptors.
      In its first randomized, placebo-controlled study, sitaxsentan improved exercise
      capacity assessed by the 6-min walk test, New York Heart Association functional
      class, cardiac index and pulmonary vascular resistance in New York Heart
      Association Class II, III and IV patients with idiopathic pulmonary arterial
      hypertension and pulmonary arterial hypertension related to connective tissue
      disease or congenital heart disease. Although doses of 100 and 300 mg once daily
      demonstrated equivalent efficacy, the lower dose had a better safety profile.
      Additional studies are ongoing to assess the relative safety and efficacy of 50
      and 100 mg once-daily dosing. The most common side effects include rhinitis,
      headache, peripheral edema, chest pain, nausea, constipation, increased
      prothrombin time/international normalized ratio (in patients on warfarin),
      flushing and insomnia. As with other endothelin receptor antagonists, increases
      in hepatic transaminases have been observed with sitaxsentan. Initial studies
      using the selective oral endothelin-A receptor antagonist sitaxsentan in
      pulmonary arterial hypertension patients have revealed a favorable risk-benefit
      therapeutic profile with the 100 mg once-daily dose.

PMID- 16292990
TI  - Isosorbide dinitrate and hydralazine hydrochloride: a review of efficacy and
      safety.
AB  - In the USA alone, there are over 5,000,000 people diagnosed with heart failure. A
      disproportionate number of African-Americans are affected by this disease, with
      increased morbidity and mortality, yet they are tremendously under-represented in
      clinical trials. Several drugs have been approved for use in heart failure based
      on clinical trials, with percentages of African-American subjects as low as 1%.
      In the African-American Heart Failure Trial the use of BiDil, a drug combining
      isosorbide dinitrate and hydralazine hydrochloride, demonstrated a 43% decrease
      in overall mortality and a 39% decrease in first hospitalization. The combination
      consists of 20 mg of isosorbide and 37.5 mg hydralazine hydrochloride in a fixed
      dose that functions as a nitric oxide enhancer and an antioxidant, and helps to
      prevent tolerance to the prolonged use of nitrate. The hemodynamic effects of the
      combination drug in heart failure includes increased cardiac output. The US Food
      and Drug Administration approved the combination of isosorbide dinitrate based on
      the African-American Heart Failure Trial. Further clinical trials utilizing
      isosorbide dinitrate will hopefully determine the benefit of this combination in
      a larger population, including caucasians and other racial/ethnic groups.

PMID- 16292991
TI  - Transcatheter occlusion of the left atrial appendage for stroke prevention.
AB  - Patients with atrial fibrillation are at an increased risk of having a
      cardioembolic stroke. Most of the thrombi responsible for these ischemic events
      originate in the left atrial appendage. Percutaneous occlusion of the left atrial
      appendage is a new approach to stroke prevention in patients with atrial
      fibrillation and contraindication for long-term warfarin treatment. Three
      different devices have been used so far: the PLAATO system, the WATCHMAN filter
      system and the Amplatzer septal occluder. Left atrial appendage occlusion using
      these devices is feasible and safe and has shown promising results. The risk of
      stroke in atrial fibrillation patients appears to be reduced.

PMID- 16292992
TI  - An image of mitral valve repair.
AB  - Mitral regurgitation is a severe problem of the mitral valve mechanism caused by
      many factors, including ischemic and nonischemic cardiomyopathy, inflammation,
      degeneration and others. Regardless of the cause of valve dysfunction, many
      changes in surgical approach have been undertaken. The pioneering work of
      Carpentier led to the era of mitral valve reconstruction a few decades ago.
      Understanding the different techniques applied in several pathoanatomic settings
      is of major interest. This review summarizes the indications and results of this
      specific surgical procedure in the setting of ventricular dysfunction by
      different causes.

PMID- 16292993
TI  - The Ross operation: utilization of the patient's own pulmonary valve as a
      replacement device for the diseased aortic valve.
AB  - Prosthetic heart valves have been outpaced by progress in cardiac surgery. Early
      biologic valve prostheses consisted of tissues mounted on a rigid stent, and did
      not require anticoagulation, but rarely survived two decades. Subsequently,
      durable mechanical valve prostheses dominated despite, the requisite
      anticoagulation. The mechanical design remains imperfect, with obstruction to
      flow, turbulence, hematological changes and also, occasionally audible clicks.
      Reports documenting superior function for cryopreserved human aortic heart valves
      (homografts) without these problems, albeit with limited durability, followed.
      The marketing of 'stentless biologic valves', mimicking these attributes was a
      reaction to the shortage of homografts. These imperfections explain the
      rediscovery of the Ross operation, in which the patient's pulmonary valve
      (autograft) is excised to replace the aortic valve. The autograft is living
      tissue, complete with attributes of a healthy heart valve, including growth and
      durability. The pulmonary valve, where lower pressure and oxygen saturation
      retards degeneration, is substituted with a pulmonary homograft. The Ross
      operation is exacting and leaves the patient with two potentially malfunctioning
      valves.

PMID- 16292994
TI  - Off-pump coronary artery bypass graft surgery: where should we stand?
AB  - Coronary artery bypass grafting (CABG) performed with cardiopulmonary bypass has
      become a well-established treatment modality for patients with coronary artery
      disease. However, there is increasing evidence that cardiopulmonary bypass may be
      responsible for some of the morbidity associated with CABG surgery. Thus, it has
      been proposed that CABG surgery would be safer if cardiopulmonary bypass could be
      avoided. The development of cardiac stabilization devices has allowed for the
      creation of safe and reproducible coronary anastomoses on the beating heart.
      Several large, non-randomized, retrospective case series have demonstrated that
      CABG surgery can be performed safely without cardiopulmonary bypass (off-pump)
      and have in fact suggested benefits when compared with conventional CABG.
      However, the randomized controlled studies published to date have, as a whole,
      been unable to conclusively demonstrate the advantages of off-pump surgery. Taken
      together, the evidence to date suggests that a large-scale, prospective,
      randomized trial may be required to resolve the dilemma.

PMID- 16292995
TI  - Myocardial protection in reperfusion with postconditioning.
AB  - Reperfusion is the definitive treatment for coronary occlusive disease. However,
      reperfusion carries the potential to exacerbate lethal injury, termed
      'reperfusion injury'. Studies have suggested that reperfusion injury events are
      triggered during the early moments of reflow, and determine, in part, the
      severity of downstream manifestations of postischemic injury, including
      endothelial dysfunction, infarction and apoptosis. The application of brief
      iterative episodes of reflow (reoxygenation) and reocclusion (ischemia, hypoxia)
      at the immediate onset of reperfusion, which has been termed 'postconditioning'
      by the authors, reduces many manifestations of postischemic injury, notably
      infarct size, apoptosis, coronary vascular endothelial injury and reperfusion
      arrhythmias. Cardioprotection with postconditioning has been reported to be
      comparable with that observed using the gold standard maneuver ischemic
      preconditioning. In contrast to preconditioning, which exerts its effects
      primarily during the index ischemia, postconditioning appears to exert its
      effects during reperfusion alone. Postconditioning modifies the early phase of
      reperfusion in ways that are just beginning to be understood. It appears to
      first: reduce the oxidant burden and consequent oxidant-induced injury; secondly,
      attenuate the local inflammatory response to reperfusion; and thirdly, engage end
      effectors and signaling pathways implicated in other cardioprotective maneuvers,
      such as ischemic and pharmacologic preconditioning. Postconditioning seems to
      trigger the upregulation of survival kinases principally known to attenuate the
      pathogenesis of apoptosis and possibly necrosis. The postconditioning phenomenon
      has been reproduced by a number of independent laboratories and has been observed
      in both large and small animal in vivo models, as well as in ex vivo and cell
      culture models. In contrast to preconditioning, postconditioning may have
      widespread clinical application because it can be applied during reperfusion at
      the point of service for angioplasty, stenting, cardiac surgery and organ
      transplantation.

PMID- 16292996
TI  - Role of clotting factors and fibrin structure in predisposition to
      atherothrombotic disease.
AB  - Atherothrombotic disease is a multifactorial disorder that develops secondary to
      a complex gene-environment interaction. The formation of an obstructive thrombus
      represents the final stage of the atherothrombotic process, and understanding the
      mechanisms involved in clot formation is essential in order to develop new
      preventive and therapeutic strategies aimed at decreasing mortality and morbidity
      from the disease. Studies have demonstrated an important correlation between
      final clot structure and predisposition to atherothrombotic disease. Both genetic
      and environmental factors contribute to the final ultrastructure of the clot,
      which, in turn, influences an individual's risk of the disease. This paper
      reviews the factors involved in determining clot structure. The role of commonly
      used therapeutic agents in modulating clot structure will also be discussed.

PMID- 16292997
TI  - Hypercholesterolemia: its impact on ischemia-reperfusion injury.
AB  - Ischemic diseases are a leading cause of death worldwide. It is becoming
      increasingly appreciated that atherosclerosis is a major cause of ischemia
      reperfusion. Hypercholesterolemia is a major risk factor for the development of
      atherosclerosis, and is associated with an increased incidence of ischemia
      reperfusion. Furthermore, elevated cholesterol levels exacerbate the vascular
      responses to ischemia-reperfusion, which intensifies the resulting organ
      dysfunction. One of the underlying features of both ischemia-reperfusion injury
      and hypercholesterolemia is the proinflammatory and prothrombogenic phenotype
      invoked in the microvasculature. This is manifested as an endothelial
      dysfunction, characterized by leukocyte and platelet recruitment, oxidative
      stress and angiotensin II receptor Type 1a activation. These common pathways of
      inflammation offer attractive targets for the development of drugs to combat
      cardiovascular disease and the associated ischemic disorders.

PMID- 16292998
TI  - Current understanding of the role of high-density lipoproteins in atherosclerosis
      and senescence.
AB  - Numerous epidemiologic and interventional studies revealed that high-density
      lipoprotein (HDL) is an important risk factor for coronary heart disease. There
      are several well documented HDL functions that may account for the
      antiatherogenic effects of this lipoprotein. The best recognized of these is the
      capacity of HDL to transport cholesterol from the periphery to the liver, and
      thereby prevent cholesterol deposition in the arterial wall. Further properties
      of HDL that may also be antiatherogenic include its potent anti oxidative and
      anti-inflammatory action. In addition, HDL seems to be involved in processes
      related to senescence at both the cellular and whole-organism level. Both protein
      components of HDL (such as apolipoprotein A-I) and its lipid components (such as,
      lysosphingolipids) appear to mediate the antiatherogenic and anti-aging effects
      of HDL. The purpose of this review is to summarize the novel functions of HDL
      that may protect from atherosclerosis and senescence.

PMID- 16292999
TI  - Aortic stenosis at young adult age.
AB  - Aortic stenosis at young adult age is usually the result of a stenotic bicuspid
      aortic valve, which is the most common cardiac congenital anomaly. In clinical
      practice, exercise and pregnancy are important topics. Furthermore, the timing of
      intervention is under debate, as little information is available on the natural
      history and outcome after aortic valve replacement in these young adults. In
      older patients, there is a trend towards earlier intervention. With the increased
      knowledge of the pathophysiology of aortic stenosis, studies have focused on the
      dilatation of the ascending aorta with risk of dissection. Recently, it has been
      suggested that pharmacologic treatment of aortic stenosis could be beneficial for
      these young adults.

PMID- 16293000
TI  - Biologic relevance of lipoxygenase isoforms in atherogenesis.
AB  - Lipoxygenases (LOXs) form a heterogeneous family of lipid-peroxidizing enzymes,
      which have originally been implicated in cell differentiation and biosynthesis of
      inflammatory mediators. More recent studies suggested a role of various LOX
      isoforms in the pathogenesis of human diseases, including bronchial asthma,
      osteoporosis and atherosclerosis. According to their phylogenetic relatedness,
      LOX-isoforms may be classified into four subfamilies, three of which (12/15-LOX,
      5-LOX, platelet 12-LOX) have been related to atherogenesis. Several lines of
      experimental evidence suggest a role for LOXs in atherosclerosis, but the
      mechanisms remain a matter of discussion. This review will briefly summarize the
      current understanding on the molecular enzymology of the LOX family and the
      current status of knowledge on the role of different LOX isoforms in
      atherogenesis. The available literature data will be critically reviewed and a
      short perspective on future developments in the field will be provided.

PMID- 16293001
TI  - Inflammation in coronary artery disease: potential role for immunomodulatory
      therapy.
AB  - Understanding of the mechanisms underlying atherosclerotic disorders has evolved
      beyond the view of a progressive collection of lipids and cellular debris in the
      vascular wall. Current evidence has implicated inflammatory pathways as an
      important pathogenic mechanism in atherogenesis and plaque destabilization.
      Although not necessarily the primary event, inflammation and cytokine activation
      during plaque formation and destabilization may represent a common final pathway
      to various stimuli. Thus, it seems that not only 'new' risk factors, such as
      infections with various microorganisms, but also classic risk factors for
      cardiovascular disease, such as hyperlipidemia, hypertension and diabetes, may
      promote their atherogenic effects through inflammatory responses. Indeed, recent
      reports have suggested that traditional cardiovascular medications may attenuate
      atherogenesis and enhance plaque stability, at least partly through anti
      inflammatory mechanisms. However, uncovering the inflammatory pathways in
      atherosclerosis has raised the possibility that newer treatment modalities should
      be more directly targeted against inflammatory mediators. Recently, a series of
      experimental studies have reported reduction of atherosclerosis by
      immunomodulatory therapy, such as chemokine blockade, interleukin-10 and
      immunization/vaccination against oxidized low-density lipoprotein and heat-shock
      protein. It is conceivable that some of these approaches will be tested
      clinically and, if successful, they could provide novel treatment strategies in
      coronary artery disease in humans.

PMID- 16293002
TI  - Genetic and environmental influences on malformations of the cardiac outflow
      tract.
AB  - Congenital cardiovascular malformations are the most common form of birth defect
      recorded. Specific malformations of the outflow portions of the heart are termed
      conotruncal malformations and arise from the septation of the common conotruncus
      of the heart. There are multiple lines of evidence that point towards genetic
      environmental interactions in the genesis of conotruncal congenital
      cardiovascular malformations. In particular, environmental exposures that involve
      vitamin A, retinol, folic acid or retinol receptors are identified as cardiac
      teratogens. Other environmental agents for which there is evidence of cardiac
      teratogenicity for outflow tract malformations include nitrofen, ambient air
      pollution, chlorinated hydrocarbons and pesticides. Genetic polymorphisms of
      xenobiotic metabolism are clearly differentiating in the effect of potential
      teratogens. Work in this field is at a new cusp, with the ability to measure
      xenobiotic exposure, document xenobiotic metabolizing genetic polymorphisms and
      integrate these data into models of cardiac teratogenesis.

PMID- 16293003
TI  - Medical device epidemiology and surveillance: patient safety is the bottom line.

PMID- 16293005
TI  - Seventh World Biomaterials Congress. 17-21 May 2004, Sydney Convention and
      Exhibition Centre, Darling Harbour, Sydney, Australia.

PMID- 16293006
TI  - Bovine valved jugular vein (Contegra) to reconstruct the right ventricular
      outflow tract.
AB  - The right ventricular outflow tract (RVOT) is the part of the circulation located
      between the right ventricle and the bifurcation of the pulmonary artery. The most
      cranial part of the right ventriculum infundibulum, the pulmonary anulus, the
      valve and finally the main trunk of the pulmonary artery are the most important
      structures. The RVOT is frequently affected in congenital heart diseases, either
      isolated, or in combination with other cardiac malformations. Current techniques
      for surgical correction of anomalies of the RVOT include repair and/or
      replacement of the pulmonary valve often combined with sub- or supravalvular
      reconstruction. The use of extracardiac conduits (homografts, stented or
      stentless xenografts) to re-establish continuity between the pulmonary ventricle
      and pulmonary artery has been an important advance in repair of complex
      congenital malformations. The Contegra (Medtronic) conduit was introduced as a
      xenograft tissue for RVOT reconstruction. This conduit has some advantages over
      homografts including availability for pediatric and adult patient sizes and
      proximal and distal cuffs allowing for extended reconstruction. The principal
      late problem related to extracardiac conduit operations is the inevitable need
      for one or more conduit replacements due to patient somatic growth or progressive
      conduit degeneration and calcification leading to stenosis.

PMID- 16293007
TI  - Dermagraft, a bioengineered human dermal equivalent for the treatment of chronic
      nonhealing diabetic foot ulcer.
AB  - Chronic nonhealing diabetic foot ulcers are a common medical problem that may
      precede severe complications such as infection, sepsis and limb loss. Current
      standard methods of treatment are aimed at removing necrotic debris, controlling
      infection, and relieving chronic pressure on the wound. Unfortunately, healing
      rates are poor with standard treatment, averaging 12-20 weeks in clinical trials.
      A new strategy for the treatment of diabetic foot ulcers has been developed
      through tissue engineering, allowing the application of healthy living skin cells
      to assist in the healing process. It is hoped that the living tissue will release
      appropriate quantities of growth factors, cytokines and other proteins to
      stimulate the chronic wound bed and accelerate healing. Dermagraft (Smith &
      Nephew) is a neonatal-derived bioengineered tissue comprised of dermal
      fibroblasts. In this article, the structure and behavior of this tissue will be
      examined, focusing particularly on the randomized clinical trials performed to
      justify its use in diabetic foot ulcers.

PMID- 16293008
TI  - Deep brain stimulation for dystonia.
AB  - Dystonia is a movement disorder characterized by involuntary muscular
      contractions that generate twisting and repetitive movements and/or abnormal
      postures. It can affect a few muscle groups (focal dystonia) or spread to most
      muscles in the body (generalized dystonia). While botulinum toxin injections can
      be successfully used to treat focal dystonias, medical options for generalized
      dystonia are very limited. Surgical therapies--and in particular deep brain
      stimulation (DBS)--are becoming the standard of care for medically intractable,
      disabling dystonias. Advantages of DBS include reversibility, adjustability and
      continued access to the therapeutic target. Initial reports describing the use of
      DBS in generalized dystonia have been very encouraging and experience in the use
      of DBS to treat various forms of dystonia is continuously growing. This article
      reviews the issues related to DBS treatment of dystonia, including proper patient
      selection, surgical approaches to target choice and device implant, a description
      of the stimulating device and its programming principles, clinical results - with
      a focus on different outcomes for primary versus secondary and generalized versus
      cervical dystonia - and complications.

PMID- 16293009
TI  - Cardiac assist devices: present status and future opportunities.
AB  - Over the last 20 years, continuous progress has been made in the technology and
      clinical applications of mechanical circulatory support systems for the treatment
      of the most severe forms of cardiac failure. In a few pioneering centers, their
      efficacy has been demonstrated in selected groups of patients. This experience
      enables assessment of the state-of-the-art devices and prediction of likely
      future developments.

PMID- 16293010
TI  - Drug-eluting stents: from evidence to policy.
AB  - Drug-eluting stents are a major breakthrough in cardiology, with the Cypher
      (Cordis Corporation) and Taxus (Boston Scientific) stents preventing 60-70% of
      repeat coronary revascularizations, compared with bare metal stents. Both
      evidence- and risk-based application of drug-eluting stents is expected to create
      relevant financial and equity problems to most public hospitals, as the cost of
      drug-eluting stents is over 1000 higher than traditional stents. In the
      perspective of third-party payers, drug-eluting stents are cost-effective
      revascularization strategies for a large portion of patients actually undergoing
      stenting. However, adequate guidelines and reimbursement strategies are still
      awaited in several countries.

PMID- 16293011
TI  - Research approaches for studying flow-induced thromboembolic complications in
      blood recirculating devices.
AB  - The advent of implantable blood recirculating devices has provided life-saving
      solutions to patients with severe cardiovascular diseases. Recently it has been
      reported that ventricular assist devices are superior to drug therapy. The
      implantable total artificial heart is showing promise as a potential solution to
      the chronic shortage of available heart transplants. Prosthetic heart valves are
      routinely used for replacing diseased heart valves. However, all of these devices
      share a common problem--significant complications such as hemolysis and
      thromboembolism often arise after their implantation. Elevated flow stresses that
      are present in the nonphysiologic geometries of blood recirculating devices,
      enhance their propensity to initiate thromboembolism by chronically activating
      the blood platelets. This, rather than hemolysis, appears to be the salient
      aspect of blood trauma in devices. Limitations in characterizing and controlling
      relevant aspects of the flow-induced mechanical stimuli and the platelet
      response, hampers our ability to achieve design optimization for these devices.
      The main objective of this article is to describe state-of-the-art numerical,
      experimental, and in vivo tools, that facilitate elucidation of flow-induced
      mechanisms leading to thromboembolism in prosthetic devices. Such techniques are
      giving rise to an accountable model for flow-induced thrombogenicity, and to a
      methodology that has the potential to transform current device design and testing
      practices. It might lead to substantial time and cost savings during the research
      and development phase, and has the potential to reduce the risks that patients
      implanted with these devices face, lower the ensuing healthcare costs, and offer
      viable long-term solutions for these patients.

PMID- 16293012
TI  - Innovative technologies for the assessment of cardiovascular medical devices:
      state-of-the-art techniques for artificial heart valve testing.
AB  - Prosthetic heart valves (PHVs) are engineered devices used for replacing diseased
      natural cardiac valves. This article presents several investigational techniques
      for the evaluation of the performance of these clinical devices, whose
      implantation is not completely free of drawbacks. The state-of-the-art in the
      technological approach for PHV testing is addressed. As the fluid dynamics of
      PHVs are particularly complex, the main focus will be on experimental
      velocimetric techniques and computational analysis. A methodology for the
      analysis of the valve's signature, in terms of its characteristic sound in the
      opening and closing phases, is also presented. The aforementioned techniques are
      necessary to guarantee an operational life of the implanted device as free as
      possible from clinical complications. It can be realistically expected that this
      characterization will help designers in improving PHV performance.

PMID- 16293013
TI  - Mechanical heart valve cavitation.
AB  - Cavitation was first directly related to mechanical heart valves in the mid 1980s
      after a series of valve failures observed with the Edwards-Duromedics valve. The
      damages observed indicated that cavitation could be responsible. Later, several
      in vitro studies visualized the bubble formation and collapse of cavitation at
      mechanical heart valves. It was suggested that cavitation could also cause damage
      to the formed elements of blood and thereby enhance the risk of thromboembolic
      complications seen in mechanical heart valve patients. Therefore, an applicable
      technique for in vivo detection of cavitation is required. This article reviews
      techniques developed for in vivo detection of cavitation and suggests focus for
      future studies.

PMID- 16293014
TI  - Nanobiotechnology: implications for the future of nanotechnology in orthopedic
      applications.
AB  - Nanotechnology involves the use of materials with components, such as fibers,
      grains and particles, that have dimensions of less than 100 nm. While numerous
      advantages of nanomaterials have been elucidated for catalytic, processing,
      mechanical, electrical, and optical applications, few have been described for
      orthopedic applications. Better orthopedic biomaterials are needed since the
      average lifetime of a bone biomaterial is less than 15 years. This review
      discusses recent studies that have been conducted to determine the efficacy of
      nanophase materials as bone implants. In doing so, it is suggested that nanophase
      materials can be synthesized to possess similar nanometer dimensions to
      components of bone tissue to promote new bone formation, compared with
      conventional orthopedic implant materials.

PMID- 16293015
TI  - Nanoparticles of biodegradable polymers for new-concept chemotherapy.
AB  - The current regimen of chemotherapy is far from satisfactory--its efficiency is
      limited and patients suffer from serious side effects. Various drug delivery
      devices have been under intensive investigation in the past few decades in
      attempts to develop controlled and targeted methods of chemotherapy
      administration. This article reviews the latest developments in nanoparticles of
      biodegradable polymers for chemotherapy of cancer and other diseases such as
      cardiovascular restenosis. The preliminary results obtained in the author's
      laboratory are used to demonstrate the concept. This review is written with the
      belief that engineering, in particular, chemical engineering principles, can be
      applied and further developed to solve the problems in the current practice of
      chemotherapy and promote a new concept of chemotherapy - chemotherapy at home.

PMID- 16293016
TI  - Gene delivery from polymer scaffolds for tissue engineering.
AB  - The combination of gene therapy with tissue engineering offers the potential to
      direct progenitor cell proliferation and differentiation into functional tissue
      replacements. Many approaches to engineering tissue replacements feature a
      polymer scaffold to create and maintain a space, support cell adhesion, and
      organize tissue formation. Polymer scaffolds, either natural, synthetic, or a
      combination of the two, have also been adapted to serve as delivery vehicles for
      viral and nonviral vectors, which can induce the expression of tissue inductive
      factors. Gene delivery is a versatile approach, capable of targeting any cellular
      process through localized expression of tissue inductive factors. The design and
      application of tissue engineering scaffolds for localized gene transfer are
      reviewed. Scaffolds are designed either to release the vector into the local
      tissue environment or maintain the vector at the polymer surface, which is
      regulated by the effective affinity of the vector for the polymer. Polymeric
      delivery can enhance gene transfer locally, promote and extend transgene
      expression, avoid vector distribution to distant tissues, and reduce the immune
      response to the vector. Scaffolds capable of controlled DNA delivery can provide
      a fundamental tool for directing progenitor cell function, which has applications
      with the engineering of numerous types of tissue. The utility of this approach
      will increase with the development of design parameters that correlate release
      and transgene expression, and with continued research into the biology of tissue
      formation.

PMID- 16293017
TI  - Vision rehabilitation in the case of blindness.
AB  - This article examines the various vision rehabilitation procedures that are
      available for early and late blindness. Depending on the pathology involved,
      several vision rehabilitation procedures exist, or are in development. Visual
      aids are available for low vision individuals, as are sensory aids for blind
      persons. Most noninvasive sensory substitution prostheses as well as implanted
      visual prostheses in development are reviewed. Issues dealing with vision
      rehabilitation are also discussed, such as problems of biocompatibility,
      electrical safety, psychosocial aspects, and ethics. Basic studies devoted to
      vision rehabilitation such as simulation in mathematical models and simulation of
      artificial vision are also presented. Finally, the importance of accurate
      rehabilitation assessment is addressed, and tentative market figures are given.

PMID- 16293018
TI  - VNS and depression: current status and future directions.
AB  - Vagus nerve stimulation (VNS) is an established anticonvulsant therapy in
      treatment-resistant patients with epilepsy. The known anatomical projections of
      the vagus nerve to many brain regions that have been implicated in mood disorders
      suggest that VNS may also have useful antidepressant effects. There has been
      growing interest in the potential application of VNS in the nonpharmacological
      management of treatment-resistant depression. Results from an open-label study,
      in which 59 subjects with treatment-resistant depression were treated for 10
      weeks with VNS therapy, reported a 31% response rate. In a recent controlled
      double-blind trial of VNS and depression, short-term treatment for 10 weeks
      failed to demonstrate statistical improvement over sham treatment. Results from
      the long-term phase of this trial may be more significant, however published data
      are awaited.

PMID- 16293020
TI  - Spine arthroplasty.

PMID- 16293021
TI  - Revival of machine perfusion: new chances to increase the donor pool?

PMID- 16293023
TI  - The XXXI European Society for Artificial Organs Congress.

PMID- 16293024
TI  - Enteryx for gastroesophageal reflux disease.
AB  - The Enteryx procedure is an endoscopic injectable treatment for the management of
      gastroesophageal reflux disease symptoms. Enteryx was approved by the US Food and
      Drug Administration in April 2003 for patients who respond to, and require daily
      pharmacologic therapy with proton-pump inhibitors. Although gastroesophageal
      reflux disease is rarely life threatening, symptoms are often chronic and
      disabling. Therefore, safe and cost-effective alternative treatments for chronic
      gastroesophageal reflux disease are sought by patients, physicians and payers.
      Multicenter clinical trials have demonstrated that the Enteryx procedure safely
      and effectively eliminates, or significantly reduces, proton-pump inhibitor use
      in approximately 84% of patients at 1 year, and 72% of patients at 2 years.

PMID- 16293025
TI  - A pen injection device for self-administration of recombinant follicle
      stimulating hormone for fertility treatments.
AB  - A pen injection device modeled on the insulin pen used by diabetic patients has
      been introduced to deliver recombinant follicle-stimulating hormone to women
      undergoing controlled ovarian stimulation for in vitro fertilization or other
      forms of assisted reproductive technology. The pen device makes it easier and
      less painful for women to self-administer daily injections. The high precision
      and accuracy of the device enables physicians to fine-tune dosage. The woman
      simply inserts the multidose cartridge into the Puregon (Follistim) Pen, attaches
      a BD Micro-Fine Pen Needle, selects the prescribed dose on the dial at the base
      of the pen, inserts the needle subcutaneously and pushes the injection button to
      administer the injection. A fresh needle is used for each injection.

PMID- 16293026
TI  - The fully automatic external cardioverter defibrillator: reality of a new
      meaningful scenario for in-hospital cardiac arrests.
AB  - Sudden cardiac death is an unresolved problem which causes significant mortality
      and morbidity in both the community and in-hospital setting. Cardiac arrest is
      often caused by ventricular tachyarrhythmias which may be mostly interrupted by
      cardioversion or defibrillation. The single most critical factor for survival is
      the response time. Over the last 30 years, there have been virtually no
      procedural changes in the way hospitals address in-hospital resuscitation. A
      unique device has been developed that eliminates human intervention and assures
      defibrillation therapy is administered in seconds. This is accomplished with a
      fully automatic, external bedside monitor defibrillator designed to be
      prophylactically attached to hospitalized patients at risk of ventricular
      tachyarrhythmia. The safety and efficacy of the device has been demonstrated in
      multicenter US and European trials. Thus, this device allows a new scenario which
      may increase survival and enables meaningful redistribution of health resources.

PMID- 16293027
TI  - Medical device research.
AB  - This perspective provides a commentary on the quality of life improvements made
      available from advances in medical device technology. An opinion of the elements
      necessary to bring innovation into medical device research is offered. In order
      to enhance the output of medical device research, strong interactive links are
      needed between clinicians and researchers to ensure research activities are
      focused on the needs of patients. Alliances with industry umbrella groups can
      support these links and facilitate the commercialization of new ideas generated
      from the research. Several forecasts for the medical device market obtained from
      other sources are also presented.

PMID- 16293028
TI  - A new machine for continuous renal replacement therapy: from development to
      clinical testing.
AB  - A new continuous renal replacement therapy machine has been designed to fulfill
      the expectations of nephrologists and intensivists operating in the common ground
      of critical care nephrology. The new equipment is called Prismaflex and it is the
      natural evolution of the PRISMA machine that has been utilized worldwide for
      continuous renal replacement therapy in the last 10 years. The authors performed
      a preliminary alpha-trial to establish the usability, flexibility and reliability
      of the new device. Accuracy was also tested by recording various operational
      parameters during different intermittent and continuous renal replacement
      modalities during 62 treatments. This article will describe our first experience
      with this new device and touch upon the historic and technologic background
      leading to its development.

PMID- 16293029
TI  - Tissue reaction to hydrophilic intraocular lenses.
AB  - The implant of intraocular lenses (IOLs) following cataract surgery induces a
      foreign body reaction to the IOL and a lens epithelial cell reaction. The host
      response to the IOL is mainly influenced by biomaterial properties. With the
      increasing use of phacoemulsification and small incision cataract surgery, there
      is growing interest in the use of foldable IOLs made of different materials.
      Hydrophilic acrylic IOLs include a wide group of foldable biomaterials different
      in terms of water content. These lenses have been reported to show a good
      biocompatibility after implantation. Nevertheless, tissue reaction to the implant
      of hydrophilic lenses is variable and not directly related to the hydrophilicity
      of their surface. A different adsorption of proteins on the IOL optic surface
      might be responsible for the different cellular reaction and lens epithelial cell
      response. Other properties besides hydrophilicity should be taken into account to
      classify IOL biomaterials.

PMID- 16293030
TI  - Innovative developments of the heart valves designed for use in ventricular
      assist devices.
AB  - Prosthetic heart valves are routinely used for replacing diseased natural heart
      valves. Even today, after five decades of prosthetic heart valve development, in
      the authors opinion the main problem associated with these valves is the risk of
      thromboembolic complications caused by unnatural hemodynamics. Further growing
      application of prosthetic heart valves is their use in the pulsatile ventricular
      assist devices (VADs). VADs may provide life-saving solutions to patients with
      severe cardiovascular diseases and are superior to drug therapy for patients with
      severe heart failure. However, the clinical applications of VADs still suffer
      from thromboembolic complications due to thrombus formations in the vicinity of
      the valves. Wherever the flow is stagnant or flow separation occurs, a thrombus
      is likely to form. The design of the heart valves with flow avoiding the
      formation of stagnant zones is one of the main goals in the development of new
      valves. This article reviews some innovative design approaches of the valves
      specially designed for use in VADs. Three design concepts are presented; one is
      based on the tilting disk valve, the second on the natural valve geometry and the
      third on the ball valve principle. However, these three different concepts have
      one common basic idea; the use of the freedom of the valve-housing design. This
      additional design freedom, which is available in VADs, is a key factor in the
      development of new valves with optimal hemodynamic performance.

PMID- 16293031
TI  - Artificial human vision.
AB  - Can vision be restored to the blind? As early as 1929 it was discovered that
      stimulating the visual cortex of an individual led to the perception of spots of
      light, known as phosphenes [1] . The aim of artificial human vision systems is to
      attempt to utilize the perception of phosphenes to provide a useful substitute
      for normal vision. Currently, four locations for electrical stimulation are being
      investigated; behind the retina (subretinal), in front of the retina
      (epiretinal), the optic nerve and the visual cortex (using intra- and surface
      electrodes). This review discusses artificial human vision technology and
      requirements, and reviews the current development projects.

PMID- 16293032
TI  - Bone reconstruction: from bioceramics to tissue engineering.
AB  - Over the past 30 years, an enormous array of biomaterials proposed as ideal
      scaffolds for cell growth have emerged, yet few have demonstrated clinical
      efficacy. Biomaterials, regardless of whether they are permanent or
      biodegradable, naturally occurring or synthetic, need to be biocompatible,
      ideally osteoinductive, osteoconductive, integrative, porous and mechanically
      compatible with native bone to fulfill their desired role in bone tissue
      engineering. These materials provide cell anchorage sites, mechanical stability
      and structural guidance and in vivo, provide the interface to respond to
      physiologic and biologic changes as well as to remodel the extracellular matrix
      in order to integrate with the surrounding native tissue. Calcium phosphate
      ceramics and bioactive glasses were introduced more than 30 years ago as bone
      substitutes. These materials are considered bioactive as they bond to bone and
      enhance bone tissue formation. The bioactivity property has been attributed to
      the similarity between the surface composition and structure of bioactive
      materials, and the mineral phase of bone. The drawback in using bioactive glasses
      and calcium phosphate ceramics is that close proximity to the host bone is
      necessary to achieve osteoconduction. Even when this is achieved, new bone growth
      is often strictly limited because these materials are not osteoinductive in
      nature. Bone has a vast capacity for regeneration from cells with stem cell
      characteristics. Moreover, a number of different growth factors including bone
      morphogenetic proteins, have been demonstrated to stimulate bone growth, collagen
      synthesis and fracture repair both in vitro and in vivo. Attempts to develop a
      tissue-engineering scaffold with both osteoconductivity and osteoinductivity have
      included loading osteoinductive proteins and/or osteogenic cells on the
      traditional bioactive materials. Yet issues that must be considered for the
      effective application of bioceramics in the field of tissue engineering are the
      degree of bioresorption and the poor mechanical strength. The synthesis of a new
      generation of biomaterials that can specifically serve as tissue engineering
      scaffolds for drug and cell delivery is needed. Nanotechnology can provide an
      alternative way of processing porous bioceramics with high mechanical strength
      and enhanced bioactivity and resorbability.

PMID- 16293034
TI  - Applications of tissue engineering in the genitourinary tract.
AB  - Congenital abnormalities and acquired disorders can lead to organ damage or loss
      of tissue within the genitourinary tract. For reconstructive purposes, tissue
      engineering efforts are currently underway for virtually every type of tissue and
      organ within the urinary tract. Tissue engineering incorporates the fields of
      cell transplantation, materials science and engineering for the purpose of
      creating functional replacement tissue. This article reviews some of the
      principles of tissue engineering and some of the applications of these principles
      to the genitourinary tract.

PMID- 16293033
TI  - The lightweight and large porous mesh concept for hernia repair.
AB  - In modern hernia surgery, there are two competing mesh concepts which often lead
      to controversial discussions, on the one hand the heavyweight small porous model
      and on the other, the lightweight large porous hypothesis. The present review
      illustrates the rationale of both mesh concepts and compares experimental data
      with the first clinical data available. In summary, the lightweight large porous
      mesh philosophy takes into consideration all of the recent data regarding
      physiology and mechanics of the abdominal wall and inguinal region. Furthermore,
      the new mesh concept reveals an optimized foreign body reaction based on reduced
      amounts of mesh material and, in particular, a significantly decreased surface
      area in contact with the recipient host tissues by the large porous model.
      Finally, recent data demonstrate that alterations in the extracellular matrix of
      hernia patients play a crucial role in the development of hernia recurrence. In
      particular, long-term recurrences months or years after surgery and implantation
      of mesh can be explained by the extracellular matrix hypothesis. However, if the
      altered extracellular matrix proves to be the weak area, the decisive question is
      whether the amount of material as well as mechanical and tensile strength of the
      surgical mesh are really of significant importance for the development of
      recurrent hernia. All experimental evidence and first clinical data indicate the
      superiority of the lightweight large porous mesh concept with regard to a reduced
      number of long-term complications and particularly, increased comfort and quality
      of life after hernia repair.

PMID- 16293035
TI  - Antibiotic impregnation of inflatable penile prostheses: effect on perioperative
      infection.

PMID- 16293037
TI  - The Zenith AAA endovascular graft.
AB  - The Zenith endovascular graft is the culmination of a worldwide collaboration of
      experts whose experience and developments were compiled, resulting in an
      endovascular prosthesis designed to treat infrarenal abdominal aortic aneurysms.
      The device is made of stainless steel, self-expanding Z-stents and polyester
      fabric. It has an uncovered stent with barbs (for fixation) that extend into the
      suprarenal aorta and is modular in design and allows for disparity in the length
      and diameter of the iliac arteries that are incorporated into the repair. A
      prospective study contrasting endovascular and open surgical patients was
      completed in 2002 and resulted in US Food and Drug Administration approval of the
      device for commercial sale within the USA. Although long-term data from the trial
      are still being evaluated, the worldwide experience with this device and its
      predicate devices has allowed for certain conclusions to be made with respect to
      performance expectations and aneurysm sac behavior. The periprocedural mortality
      in healthy patients with anatomy meeting the device instructions for use should
      be under 2%. The expected risk of endoleak (mostly Type II) was 7.4% at 12 months
      and 5.4% at 24 months. Migration (based on the reporting standards for
      endovascular aneurysm repair recommended by the vascular surgical societies,
      published in the Journal of Vascular Surgery in 2001) was not seen in any
      patients over 12 months. The majority of the aneurysms shrink at 1 and 2 years,
      and any patient exhibiting aneurysm growth had a detectable cause and required
      treatment. Coupled with European and Australian data, including several device
      explants, the device integrity issues are limited to barb separation (which has
      about a 2% incidence and appears incidental in the US trial) and suprarenal stent
      detachment (six cases detected worldwide). In order to address the latter
      problem, a design alteration was implemented with a double suture attachment,
      significantly increasing the tensile strength of the device. No separations have
      been noted since the change instituted at the conclusion of the US trial.

PMID- 16293038
TI  - Current status and future of implantable insulin pumps for the treatment of
      diabetes.
AB  - The data from the Diabetes Control and Complications Trial show that control of
      blood glucose with intensive insulin therapy significantly delays complications
      of diabetes when compared with conventional therapy consisting of one or two
      insulin injections per day. However, the subcutaneous intensive insulin therapy,
      including insulin infusion by external pumps, required to achieve the glycemic
      goals defined by the Diabetes Control and Complications Trial, led to an
      increased frequency of severe hypoglycemia. Improvements in parenteral insulin
      therapy are possible by either modifying subcutaneous insulin kinetics (insulin
      analogs) or developing better routes of administration. Intraperitoneal insulin
      infusion offers a more physiologic route of insulin delivery. The ultimate goal
      for the treatment of diabetes remains the development of a fully automated
      glucose-controlled device.

PMID- 16293039
TI  - Radiofrequency catheter ablation of Type 1 atrial flutter using a large-tip
      electrode catheter and high-power radiofrequency energy generator.
AB  - Recent studies have demonstrated a high degree of efficacy of 8 mm electrode
      tipped or saline-irrigated-tip catheters for ablation of atrial flutter (AFL).
      These catheters have a theoretical advantage as they produce a large ablation
      lesion. However, large-tip ablation catheters have a larger surface area and
      require a higher power radiofrequency (RF) generator with up to 100 W capacity to
      produce adequate ablation temperatures (50-60 degrees C). The potential
      advantages of a large-tip ablation catheter and high-power RF generator include
      the need for fewer energy applications, shorter procedure and fluoroscopy times,
      and greater efficacy. Therefore, the safety and efficacy of AFL ablation using 8
      or 10 mm electrode catheters and a 100-W RF generator was studied using the
      Boston Scientific, Inc., EPT-1000 XP cardiac ablation system. There were 169
      patients, aged 61 +/- 12 years involved. Acute end points were bidirectional
      isthmus block and no inducible AFL. Following ablation, patients were seen at 1,
      3 and 6 months, with event monitoring performed weekly and for any symptoms.
      Three quality of life surveys were completed during follow-up. Acute success was
      achieved in 158 patients (93%), with 12 +/- 11 RF energy applications. The
      efficacy of 8 and 10 mm electrodes did not differ significantly. The number of RF
      energy applications (10 +/- 8 vs. 14 +/- 8) and ablation time (0.5 +/- 0.4 vs.
      0.8 +/- 0.6 h) were less with 10 mm compared with 8 mm electrodes (p < 0.01). Of
      158 patients with acute success, 42 were not evaluated at 6 months due to study
      exclusions. Of the 116 patients evaluated at 6 months, 112 (97%) had no AFL
      recurrence. Of those without AFL recurrence at 6 months, 95 and 93% were free of
      symptoms at 12 and 24 months, respectively. Ablation of AFL improved quality of
      life scores (p < 0.05) and reduced anti-arrhythmic and rate control drug use (p <
      0.05). Complications occurred in six out of 169 patients (3.6%) but there were no
      deaths. It was concluded that ablation of AFL with 8 or 10 mm electrode catheters
      and a high-power RF generator was safe, effective and improved quality of life.
      The number and duration of RF applications was lower with 10 mm compared with 8
      mm electrode catheters.

PMID- 16293040
TI  - Currently available metacarpophalangeal prostheses: their designs and prospective
      considerations.
AB  - Although implanted for over 40 years, finger prostheses have failed to match the
      success achieved by artificial hip and knee prostheses, despite a myriad of
      designs having been proposed and implanted. This article looks at the currently
      available designs of metacarpophalangeal prosthesis, both single-piece and
      multicomponent implants. An appraisal of their designs and the clinical results,
      where available, are provided. The review also considers the challenges that are
      still faced by bioengineers and surgeons concerned with improving the success of
      metacarpophalangeal prostheses. In addition, key current areas of concern such as
      in vitro testing and contemporary issues in rheumatology, which may be
      diminishing the amount of metacarpophalangeal arthroplasty taking place, are
      discussed.

PMID- 16293041
TI  - Injection therapy for stress urinary incontinence in adult women.
AB  - Stress urinary incontinence (SUI) is prevalent in adult women and has a
      considerable impact on quality of life. However, it often remains undiagnosed and
      therefore untreated. Noninvasive treatment is likely to be offered in mild cases
      and may entail pelvic floor muscle re-education, minimally invasive devices or
      pharmacotherapy. Surgical intervention is widely considered as the only effective
      option for more severe SUI, although it is not suitable for all patients.
      Injection therapy with urethral bulking agents represents an alternative
      minimally invasive procedure and can be used for all types of SUI. Many bulking
      agents have been developed, although the ideal remains to be discovered. The
      safety and durability of agents remain a concern. No differences in agents from
      an efficacy point of view have been found. For many years urethral injection
      could only be administered endoscopically. The recent development of devices for
      blind injection has increased the speed and convenience of urethral injection,
      removing the need for surgical facilities. The subjective cure rate after
      injection therapy is higher than the objective one. A focus on the patient's
      wishes and expectations with respect to success and risks of a treatment for SUI
      is required. In addition, randomized clinical trials are mandatory to establish
      the place and efficacy of urethral bulking agents compared with conservative
      therapy (pelvic floor muscle re-education) in treating SUI in adult women.

PMID- 16293042
TI  - Temporary or permanent support and replacement of cardiac function.
AB  - Cardiac assist devices are classified into the traditional engineering categories
      of displacement and rotary pumps. Clinical use and indications of the various
      pump categories are outlined and a detailed description of the currently
      available systems is given. The first section deals with extracorporeal as well
      as implantable ventricular assist devices of the displacement type and is
      followed by a section on current developments in the field of total artificial
      hearts. The latter part of the article covers the rotary pump category from
      cardiopulmonary bypass applications to implantable systems, including specific
      design aspects of radial, diagonal and axial pumps.

PMID- 16293043
TI  - Bioabsorbable fixation devices in trauma and bone surgery: current clinical
      standing.
AB  - Bioabsorbable fixation devices are increasingly used in trauma, orthopedic and
      craniomaxillofacial surgery. The devices are essentially made of polylactic acid
      and/or polyglycolic acid polymers. Ultra-high-strength implants are manufactured
      from such polymers using self-reinforcing techniques. Implants are available for
      stabilization of fractures, osteotomies, bone grafts and fusions, as well as for
      reattachment of ligaments, tendons, meniscal tears and other soft tissue
      structures. As these implants are completely absorbed, the need for a removal
      operation is overcome and long-term interference with tendons, nerves and the
      growing skeleton is avoided. The risk of implant-associated stress shielding,
      peri-implant osteoporosis and infections is reduced. Implants do not interfere
      with clinical imaging. Current clinical use of bioabsorbable devices is reviewed.

PMID- 16293044
TI  - Bioartificial tracheal grafts: can tissue engineering keep its promise?
AB  - A huge variety of graft materials and transplantation approaches have been
      applied for decades in order to generate a clinically applicable tracheal
      substitute; so far, without success. Today, tissue engineering, the creation of
      man-made functional biological organs or tissue replacements from biodegradable
      carrier structures and autologous cells, may represent an alternative to the
      shortage of suitable grafts for reconstructive airway surgery. Partial success
      has been obtained by numerous groups following different concepts and strategies.
      In this article, tissue engineering approaches towards the bioartificial airway
      prosthesis are discussed, focusing primarily on recent developments in the field.

PMID- 16293045
TI  - Total anterior corneal surface and epithelial stem cell harvesting: current
      microkeratomes and beyond.
AB  - Currently, most corneal lamellar allografts are performed by manually dissecting
      donor corneoscleral material for transplantation. Manual dissection is
      technically challenging and time intensive, and excessive handling of tissue may
      decrease the likelihood of obtaining viable grafts. These mechanical factors,
      along with problems controlling immune rejection, have prevented limbal stem cell
      lamellar allografts in particular from becoming more widely used. Anterior
      lamellar keratoplasty is gaining in clinical importance and usage but is still
      only practiced by a limited number of surgeons. Recently, new mechanical and
      femtosecond laser microkeratomes have been adapted to harvest the anterior
      corneal surface, including the limbal stem cell region. Preliminary results have
      been encouraging and give hope that this technique may prove to be of benefit to
      patients in the future.

PMID- 16293046
TI  - Technological advances in nanoscale biomaterials: the future of synthetic
      vascular graft design.
AB  - Currently, autologous veins are the first choice for patients in need of bypass
      grafting materials. However, due to either pre-existing conditions or previous
      bypass surgery, some patients lack the necessary amount of host tissue for such
      procedures. Unfortunately, current synthetic vascular grafts of less than 6 mm in
      diameter have been plagued by a variety of problems. For this reason, there has
      been significant research aimed at finding more suitable small-diameter vascular
      graft materials. In order to improve vascular cell functions on such synthetic
      materials, several techniques are currently under development that attempt to
      mimic the natural nanometer architecture of the vascular basement membrane. This
      review presents several processes including colloidal lithography, chemical
      etching, electrospinning and solid free-form fabrication that could play a role
      in the future of vascular nanostructured biomaterial development.

PMID- 16293047
TI  - Nursing and biomedical engineering transdisciplinary clinical trials
      collaboration.

PMID- 16293049
TI  - Use of the MicroMed DeBakey VAD for the treatment of end-stage heart failure.
AB  - Congestive heart failure poses a serious health risk to millions of Americans.
      Medical therapy for advanced stages of this condition has offered a minimal
      benefit and surgical treatment through transplantation is limited by the donor
      organ shortage. Although left ventricular assist devices may represent the future
      of therapy for this disease, the first generation of these pumps are limited by a
      number of factors that restrict their use to only the sickest of patients. The
      development and clinical use of the MicroMed DeBakey VAD represents a paradigm
      shift in the field of heart disease, supporting the notion that mechanical
      assistance can be achieved with continuous flow pumps. Axial flow devices, such
      as the DeBakey VAD, may open new doors for smaller patients and children, as well
      as improve the current standard of care for adults who require long-term
      circulatory support.

PMID- 16293051
TI  - Diameter-dependent excitation of peripheral nerve fibers by multipolar electrodes
      during electrical stimulation.
AB  - Neural prostheses are technical devices that interface the nervous system to
      restore lost body functions by means of electrical stimulation, and to increase
      the activities of daily living of disabled persons--at least to some extent. One
      of the major reasons for the limited performance of neural prostheses is caused
      by the inverse recruitment of axons via excitation, by means of electrical
      stimulation. Due to their biophysical properties, electrical stimulation excites
      axons according to their diameter, starting with large-diameter fibers. This is
      the inverse order with respect to physiologic recruitment. It causes muscle
      fatigue, dyssynergia and limited muscle force control, respectively. A new
      electrode arrangement, with longitudinal multipolar stimulation, allows the
      selection of fiber diameters by its design with rectangular stimulation pulses
      and a reasonable amount of charge per phase. This report discusses the impact of
      the new approach in comparison with other stimulation paradigms to obtain fiber
      selective nerve activation and its opportunities for neural prostheses in context
      with miniaturization trends in implant technology.

PMID- 16293050
TI  - Accuray CyberKnife image-guided radiosurgical system.
AB  - Radiosurgery is the application of radiation therapy in an extremely precise
      manner. These techniques apply large bioequivalent doses of radiation to a small
      area in order to destroy tumor cells, while sparing surrounding normal tissues.
      Radiosurgery has been available for intracranial abnormalities since the 1950s
      but it has only recently become available to treat tumors outside of the brain
      and skull base. This article outlines the authors experience with CyberKnife in
      the treatment of spinal and spine-associated abnormalities.

PMID- 16293052
TI  - Preparation, indications and results of human amniotic membrane transplantation
      for ocular surface disorders.
AB  - In comparison with other biologic tissues used as reconstructive grafts, the
      amniotic membrane has the advantage that it is thinner and better tolerated by
      the patient. Amniotic membrane, when appropriately preserved, can be used as a
      substrate replacement, such that host cells can migrate into the membrane to form
      new and healthy tissue. The amniotic membrane is the deeper layer of the fetal
      membrane; it is avascular, multilayered tissue with antiangiogenic, antiscarring
      and anti-inflammatory properties. Since it does not express antigens of
      histocompatibility, the membrane is never rejected by the receiving tissues. In
      addition, the beneficial effects of reducing inflammation and neovascularization
      persist for a long time, if properly cryopreserved.

PMID- 16293054
TI  - Improving the lives of patients with medically refractory epilepsy by electrical
      stimulation of the nervous system.
AB  - Vagal nerve stimulation proved effective in animal models of epilepsy, and in
      open and double-blinded trials, in over 450 patients. Seizure reduction improved
      for at least 2 years. Almost 50% of treated patients achieve at least a 50%
      reduction in seizure frequency. Other advantages include termination of a seizure
      and improved alertness. Benefits were demonstrated in children, partial and
      generalized epilepsies, and in specific neurologic syndromes.

PMID- 16293053
TI  - The intraocular lens: challenges in the prevention and therapy of infectious
      endophthalmitis and posterior capsular opacification.
AB  - Cataract is the leading cause of visual impairment worldwide. In the UK, some 30%
      of the population over 65 years of age have visually impairing cataract.
      Importantly, 88% of those with treatable visual impairment from cataract are not
      in contact with any ocular healthcare service, representing a major potential
      healthcare need [1]. In the USA, it has been estimated that 17.2% of the
      population (approximately 20.5 million) over 40 years of age have cataract in
      either eye and by 2020, this number is expected to rise to 30.1 million.
      Currently, cataract is responsible for 60% of Medicare costs associated with
      vision [2]. Furthermore, as the populations of industrialized countries such as
      the UK and the USA continue to age, the costs associated with treatment of
      cataract can only be expected to increase. Consequently, the development of the
      intraocular lens to replace the cataractous lens and the advances in intraocular
      lens design and implantation represent a major development in cataract treatment.
      However, despite such advances, cataract surgery is not without complications,
      such as postoperative infectious endophthalmitis, a rare but potentially
      devastating condition, and posterior capsular opacification, a less serious but
      much more common problem. This review will examine the epidemiology of cataracts,
      the polymeric construction of intraocular lenses implanted during cataract
      surgery and the complications of postoperative infectious endophthalmitis and
      posterior capsular opacification with regard to therapeutic interventions and
      prophylactic strategies. Advances in biomaterial design and function will be
      discussed as novel approaches to prevent such postoperative complications.

PMID- 16293055
TI  - Scintimammography for the detection of breast cancer.
AB  - Scintimammography is a functional imaging technique whereby radionuclide tracers
      in the patient's breasts are observed with a radiation-detection camera (gamma
      camera). Tracers are designed to accumulate in tumors more than in healthy
      tissue; the most common tracers used to date are Tc-99m sestamibi and Tc-99m
      tetrofosmin. Scintimammography is useful in some clinical indications as an
      adjunct to mammography and to reduce the rates of negative biopsies, and it is
      recommended for lesions where additional information is required to reach a
      definitive diagnosis. Patients with equivocal mammograms may benefit from this
      test, as well as women with dense breasts and those with implants, since
      scintigraphy is not affected by breast density and the photons arising from the
      radiotracer are not overly attenuated by implants. Scintimammography is also of
      value in patients with locally advanced breast cancer, for monitoring and
      predicting the response to neoadjuvant chemotherapy. The near availability of
      high-resolution breast-dedicated cameras will allow the suboptimal sensitivity in
      detecting cancers of less than 1 cm to be improved; this is currently the main
      limitation of scintimammography. These new devices also have the potential to
      increase the number of breast scintigraphies performed and the role of nuclear
      medicine in breast cancer imaging.

PMID- 16293056
TI  - Aerosol delivery devices and obstructive airway disease.
AB  - Two obstructive lung diseases, asthma and chronic obstructive pulmonary disease,
      account for the vast majority of prescriptions for aerosolized medications and
      devices . Asthma is an immunologically mediated condition characterized by
      episodic reversible airway obstructions that occur in all age groups. In
      contrast, chronic obstructive pulmonary disease is a condition characterized by
      relatively irreversible obstruction that is seen in middle-aged and elderly
      cigarette smokers. Nevertheless, there is sufficient overlap in terms of airway
      physiology and therapeutics to allow a review of the challenge of aerosol
      delivery in both conditions in the same article. This review will concentrate on
      issues related to aerosol delivery.

PMID- 16293057
TI  - High-resolution, in vivo retinal imaging using adaptive optics and its future
      role in ophthalmology.
AB  - Until recently it was impossible to fully realize the optical resolution afforded
      by the human eye due to the inherent optical aberrations. These aberrations limit
      the ability to see fine structure in the retinal layers and visual perception of
      the outside world. A conventional spectacle or contact lens refraction only
      provides a static amelioration of the lowest order aberrations, namely defocus
      and astigmatism. In addition, all of these distortions are constantly evolving
      due to changes in accommodation and head/eye movements. The technique of adaptive
      optics not only corrects all of the static spatial modes but also measures and
      corrects any dynamic changes. Such systems have allowed for routine in vivo
      cellular imaging, the classification of individual photoreceptor cells and have
      enabled psychophysical testing of human visual function at the neural level. This
      review introduces the principle of adaptive optics and the key hardware required
      to implement such a scheme. The integration of adaptive optics into different
      imaging modalities is presented along with descriptions of current systems in use
      today and the experimental results obtained to date. Finally, the review
      concludes by discussing future technology and gives the author's prediction of
      how the field will evolve over the coming years.

PMID- 16293058
TI  - Recent advances in sonographic imaging of fetal thoracic structures.
AB  - Recent ultrasonographic methods applied in the evaluation of fetal thoracic
      structures and anomalies are presented. Fetal lung volumetric assessment by 3D
      ultrasonography, analysis of the thoracic wall by 3D-rendered image and 3D
      skeletal-mode imaging, intrathoracic vessel evaluation by 3D power Doppler
      ultrasonography, analysis of heart anatomy and abnormalities by 4D spatiotemporal
      image correlation, identification of normal and abnormal intrathoracic almost
      isoechogenic structures by volume contrast imaging and evaluation of the heart
      and great vessels by 3 and 4D inverse mode will be reviewed.

PMID- 16293059
TI  - Anastomotic devices for coronary artery bypass grafting.
AB  - With the advent of off-pump and minimally invasive coronary artery bypass
      grafting, efforts to facilitate construction of the graft to coronary anastomosis
      have increased. As a result, a number of anastomotic devices have been developed.
      While the ideal anastomotic device should be easy to use, produce a geometrically
      optimal anastomosis with minimal endothelial damage and minimal blood-exposed
      nonintimal surface, a number of design constraints apply. This review collects
      the available preclinical and clinical data for some of the devices, with special
      regard as to surgical outcome, patency rate and the need for additional
      perioperative anticoagulation treatment.

PMID- 16293060
TI  - Education, bioMEMS and the medical microdevice revolution.

PMID- 16293063
TI  - HeartMate II left ventricular assist device: a new device for advanced heart
      failure.
AB  - Since the initial use of artificial heart devices decades ago, advances in
      technology have yielded new artificial heart devices that can finally achieve the
      goal of providing life-saving treatment and good quality of life in terminally
      ill patients with heart failure. The HeartMate II left ventricular assist device
      is a new generation of device that is small, quiet and relatively easy to
      implant. A pilot study in the USA recently completed enrollment, and the pivotal
      trial is now underway to study this device in patients who are awaiting
      transplant and patients who are not candidates for transplant. To date, the
      results look promising that this device may be widely applicable to patients who
      have heart failure that do not respond to conventional treatments.

PMID- 16293062
TI  - Edwards FloTrac sensor and Vigileo monitor: easy, accurate, reliable cardiac
      output assessment using the arterial pulse wave.
AB  - Edwards Lifesciences has recently introduced the FloTrac sensor and Vigileo
      monitor system for monitoring cardiac output continuously. It does not require
      thermodilution or dye dilution, but rather bases its calculations on arterial
      waveform characteristics in conjunction with patient demographic data. It is
      unique among arterial waveform cardiac output systems in that it does not require
      calibration with another method. Studies thus far indicate that it is robust and
      accurate over a wide range of cardiac output and clinical conditions. It will be
      valuable in the care of many patients, such as those with critical illness,
      cardiovascular dysfunction, trauma or undergoing major surgery.

PMID- 16293064
TI  - Treatment of Meniere's disease with the low-pressure pulse generator (Meniett
      device).
AB  - Until recently, surgery was the only treatment option for people with disabling
      Meniere's disease that did not respond to adequate medical therapy. A new
      intermediate level treatment modality, the Meniett device, which applies low
      pressure micropulses to the inner ear, has now been shown to be safe and
      effective. The device is portable and self-administered, requiring a 5-min three
      times daily application for an indefinite period. Placement of a tympanostomy
      tube in the ear drum of the affected ear is necessary. Patient acceptance has
      been high. Long-term success in control of vertigo is over 80%. Although hearing
      loss is not improved, Meniett device usage does not adversely affect balance, as
      do most forms of surgical therapy. Use of the device does not preclude later
      surgical therapy.

PMID- 16293065
TI  - Development of medical devices for neuro-interventional procedures: special focus
      on aneurysm treatment.
AB  - Since the introduction of the Guglielmi detachable coil in 1990, the role of
      endovascular treatment for intracranial aneurysm has changed significantly.
      However, this endovascular modality has intrinsic technical limitations in wide
      neck and large (11-25 mm) or giant (>25 mm) aneurysms. Long-term anatomic
      outcomes for these aneurysms include an approximate 25% recanalization rate.
      Since the aneurysm recanalization is related to morphologic, hemodynamic and
      biologic factors associated with aneurysm healing, improvement of these factors
      has elicited several technical modifications of the original technique. This
      review will describe new endovascular devices that have been manufactured to
      improve the technical limitations inherited by the Guglielmi detachable coil
      technique, as well as the historic background of endovascular treatment for
      cerebral aneurysms.

PMID- 16293066
TI  - Influence of new technologies on thyroid surgery: state of the art.
AB  - The history of thyroid surgery starts with Billroth, Kocher and Halsted, who
      developed the technique for thyroidectomy between 1873 and 1910. In general, the
      essential objectives for thyroidectomy are conservation of the parathyroid
      glands, avoidance of injury to the recurrent laryngeal nerve, an accurate
      hemostasis and an excellent cosmesis. In the last 20 years, major improvements
      and new technologies have been proposed and applied in thyroid surgery; among
      these are mini-invasive thyroidectomy, new devices for achieving hemostasis and
      dissection, regional anesthesia and intraoperative neuro-monitoring.

PMID- 16293068
TI  - Computed tomography: important considerations for pediatric patients.
AB  - Computed tomography plays a central and increasingly important role in medical
      imaging. From the very beginning more than 30 years ago, computed tomography
      technology has continued to develop and provide a wide variety of applications
      for evaluation of disorders of virtually any organ system in both children and
      adults. The benefits are particularly evident with the newer, fast, high
      resolution multidetector scanners. However, these benefits must be carefully
      weighed against the potential risks, which include a relatively high radiation
      dose. Current research efforts are directed at both further improvements in the
      diagnostic potential with computed tomography, as well as managing radiation
      dose.

PMID- 16293067
TI  - Medical applications of electronic nose technology.
AB  - Electronic nose technology has been developed over the past 15 years in the field
      of chemistry as an electronic equivalent of the biologic mechanism of smell.
      Since its inception, it has been well recognized that there is great potential in
      applying this technology to the field of medicine. This review discusses those
      areas of medicine in which electronic nose technology has been applied. For each
      area, this review addresses the scope of the medical problem that has been
      studied, how the electronic nose technology may help address the medical problem,
      and the results of such studies to date. Next generation electronic noses will be
      refined to better analyze specific disease states. This will require further
      evaluation of the specific volatiles to be tested. This information may then be
      brought to bear on refinement of the chemistry of the electronic nose sensors,
      making them more sensitive and specific for the particular disease of interest.
      The ultimate goal of work in this arena is to make an electronic nose that is
      portable, fast, inexpensive and, therefore, suitable for use in the examination
      room or at the bedside, making it facile as a diagnostic tool.

PMID- 16293070
TI  - Diagnosis of small-bowel diseases in the era of capsule endoscopy.
AB  - Capsule endoscopy is a major breakthrough in gastrointestinal endoscopy and is a
      first-line tool to detect abnormalities of the small bowel, in up to 50% of
      patients, intestinal disorders are not associated with any physical findings or
      positive tests. Indications, yield and impact on patient management of this
      method of diagnosing small-bowel diseases are analyzed critically in light of
      current scientific knowledge.

PMID- 16293069
TI  - Diaphragm pacers as a treatment for congenital central hypoventilation syndrome.
AB  - Congenital central hypoventilation syndrome is a rare syndrome present from
      birth, and is defined as the failure of automatic control of breathing. All
      patients with congenital central hypoventilation syndrome require life-long
      ventilatory support during sleep, although approximately a third of patients
      require ventilatory support 24 h per day. Diaphragm pacers offer a modality of
      ventilatory support that affords congenital central hypoventilation syndrome
      patients with maximal mobility for full-time ventilatory patients, and they may
      allow for a more normal lifestyle in the appropriate patient. They may permit
      tracheostomy decannulation in those requiring only support during sleep.
      Diaphragm pacing entails surgical placement of an electrode onto the phrenic
      nerve, connected to a subcutaneous receiver. There is an external battery
      operated transmitter and antenna placed on the skin over the receiver. The
      transmitter emits energy, similar to radio transmission, which is converted into
      an electrical current by the receiver. This stimulates the phrenic nerve
      resulting in a diaphragmatic contraction. Settings on the transmitter include
      respiratory rate and electrical voltage, and are adjusted to give enough tidal
      volume to allow for adequate oxygenation and ventilation. Therefore, diaphragm
      pacing is an attractive alternative mode of mechanically assisted ventilation for
      many patients with congenital central hypoventilation syndrome.

PMID- 16293071
TI  - Staple-line buttressing material in gastric-bypass surgery.
AB  - The problem of obesity has reached epidemic proportions in the USA. More than 50%
      of adults are obese or overweight. The only therapeutic intervention that
      provides effective long-term weight loss for the severely obese is bariatric
      surgery. Roux-en-Y gastric bypass is the most commonly performed bariatric
      operation in the USA. Anastomotic leaks can cause life-threatening sepsis in the
      immediate postoperative period or delayed presentations with fistulas. Fibrin
      sealant and bovine pericardium have been used to reinforce the anastomosis in
      order to decrease the rate of this dreaded complication. This review will
      summarize current literature on the subject.

PMID- 16293072
TI  - Color Doppler sonography in obstetrics and gynecology.
AB  - This review aims to provide the reader with an overview of the present and future
      clinical applications in color Doppler sonography for the evaluation of
      vascularity and blood flow within the uterus (both gravid and nongravid),
      ovaries, fetus and placenta. The clinical use of color Doppler sonography has
      been demonstrated within many organ systems. Color Doppler sonography has become
      an integral part of cardiovascular imaging. Significant improvements have
      recently occurred, improving the visualization and evaluation of intra-organ
      vascularity, resulting from enhancements in delineation of tissue detail through
      electronic compounding and harmonics, as well as enhancements in signal
      processing of frequency- and/or amplitude-based color Doppler sonography. Spatial
      representation of vascularity can be improved by utilizing 3D and 4D (live 3D)
      processing. Greater sensitivity of color Doppler sonography to macro- and
      microvascular flow has provided improved anatomic and physiologic assessment
      throughout pregnancy and for pelvic organs. The potential use of contrast
      enhancement is also mentioned as a means to further differentiate benign from
      malignant ovarian lesions. The rapid development of these new sonographic
      techniques will continue to enlarge the scope of clinical applications in a
      variety of obstetric and gynecologic disorders.

PMID- 16293073
TI  - Transobturator approach to suburethral sling placement in the treatment of stress
      urinary incontinence in women.
AB  - Minimally invasive suburethral sling procedures have become a mainstay for the
      surgical treatment of stress urinary incontinence in women. The transvaginal tape
      sling is the urethral sling most commonly used today. Although the transvaginal
      tape procedure is safe and efficacious, complications such as bladder, bowel and
      blood vessel injury have been reported. The most promising recent innovation in
      minimally invasive surgery for stress urinary incontinence is the transobturator
      approach for sling placement. This review will cover the mechanism of continence,
      rationale for the use of suburethral slings in the treatment of stress urinary
      incontinence, characteristics of polypropylene, comparison of the slings that are
      commercially available and early data on the efficacy of the transobturator
      approach in the treatment of stress urinary incontinence.

PMID- 16293074
TI  - Currently available devices for female sterilization.
AB  - Sterilization is now the method of family planning most commonly used in the
      world. Over the last 150 years, research has evolved in the search for the ideal
      method of female sterilization. The procedure should ideally have high efficacy,
      be readily accessible and be personally and culturally acceptable. The method
      should be simple, quick, easily learned and be able to be performed in an
      outpatient setting without general anesthesia. The most common and effective
      method for sterilization has, thus far, been via the laparoscopic route.
      Hysteroscopic sterilization, however, potentially fulfills many of these ideal
      criteria, but until recently has remained more of a concept than a reality.

PMID- 16293075
TI  - An update on second-generation devices for endometrial ablation.
AB  - Menorrhagia is a very common problem. Hysterectomy has been the traditional
      surgical treatment of choice guaranteeing amenorrhoea. It is 100% effective but
      is associated with surgical complications, and is more costly in terms of
      economic impact and recovery time. Minimally invasive procedures to ablate the
      endometrium reduce complications and recovery time. The newer second-generation
      endometrial ablation devices negate the need for surgery under direct
      hysteroscopic vision, thus ensuring that the treatments are not operator
      dependent. However, they heavily rely on the device themselves to ensure safety
      and efficacy. There are a variety of these devices currently available on the
      market. The authors will review these devices and provide the evidence for their
      suitability in various settings.

PMID- 16293076
TI  - Galvani's delayed legacy: neuromuscular electrical stimulation.

PMID- 16293078
TI  - MammoSite.
AB  - MammoSite is a novel brachytherapy applicator for breast irradiation as a
      component of breast conservation therapy in the management of early stage breast
      carcinoma. Early stage breast cancer accounts for over two-thirds of newly
      diagnosed cases. Breast conservation therapy is an option for most women for
      local therapy. The standard treatment of partial mastectomy and whole-breast
      irradiation is being challenged. Physicians and patients are searching for
      alternatives to a 6- to 7-week course of external beam radiation therapy. The
      direct application of radioactive materials (brachytherapy) in this setting has
      been employed for over 10 years. MammoSite has been developed as an easier, more
      quality assured applicator to allow broader acceptance and wider availability of
      partial breast irradiation techniques. The background leading to the device will
      be examined, current clinical results will be reviewed and alternative
      technologies will be discussed.

PMID- 16293080
TI  - Safety considerations for deep brain stimulation: review and analysis.
AB  - Deep brain stimulation has emerged rapidly as an effective therapy for movement
      disorders. Deep brain stimulation includes an implanted brain electrode and a
      pacemaker-like implanted pulse generator. The clinical application of deep brain
      stimulation proceeded in the absence of clear understandings of its mechanisms of
      action or extensive preclinical studies of safety and efficacy. Post mortem
      studies suggest that there is a loss of neurons in proximity to the active
      electrode, but the resulting lesions are not sufficient to treat the disorder and
      efficacy requires continued stimulation. Overall complication rates can exceed
      25%, and permanent neurologic sequelae result in 4-6% of cases. As the
      application of deep brain stimulation expands, it is critical to understand the
      origin of adverse events and the delivery of nondamaging stimulation.

PMID- 16293079
TI  - Computer-aided surgery of the paranasal sinuses and skull base.
AB  - Endoscopic sinus surgery is one of the most common surgical procedures in
      otolaryngology. However, the location of the orbit and intracranial contents in
      close proximity to the paranasal sinuses makes endoscopic sinus surgery
      potentially hazardous. Otolaryngologists have employed computer-aided surgery, or
      image-guided surgery, over the past two decades to enhance surgeon confidence,
      allow more thorough surgical dissections and possibly reduce the complication
      rate of endoscopic sinus surgery. Computer-aided surgery utilizes preoperative
      imaging to provide real-time localization of surgical instruments in the surgical
      field. Although computer-aided surgery originated in the neurosurgical realm,
      otolaryngologists soon appreciated that this technology could assist in
      identifying critical orbital or intracranial structures surrounding the paranasal
      sinuses, and potentially aid in decreasing complications. In this article, the
      history of image-guidance systems and their application to surgery of the
      paranasal sinuses and skull base will be reviewed. The components of computer
      aided surgery systems and the currently available technologies for surgical
      instrument tracking are discussed, as well as the advantages and disadvantages of
      each of the tracking technologies. In addition, issues relating to the accuracy
      of image-guidance systems are examined. A number of institutional series noting
      surgeon experience with computer-aided surgery in the domain of paranasal sinus
      surgery are reviewed. Furthermore, the authors evaluate the utility of image
      guidance technology beyond the paranasal sinuses and skull base, such as its use
      in surgery of the pituitary gland and pterygopalatine fossa, research and
      resident education. Finally, potential future applications of computer-aided
      surgery technology are discussed.

PMID- 16293081
TI  - Ganciclovir implant in the treatment of cytomegalovirus retinitis.
AB  - The ganciclovir implant is a sustained-release intraocular drug delivery system
      used to treat cytomegalovirus retinitis that provides a high and steady-state
      concentration of the drug in the vitreous cavity over a period of 7-8 months.
      Randomized, controlled clinical trials have demonstrated a superior efficacy of
      the implant compared with intravenous ganciclovir. Severe adverse events
      associated with the implant are uncommon, though potentially blinding. In
      addition, the implant provides no protection against second-eye or visceral
      cytomegalovirus retinitis infections. This review summarizes the clinical
      indications for and complications associated with the ganciclovir implant.

PMID- 16293082
TI  - Interfacial biology of in-stent restenosis.
AB  - Percutaneous angioplasty is a nonsurgical method able to restore patency in
      atherosclerotic blood vessels through the expansion of a balloon. The clinical
      outcome of this technique has been significantly enhanced by the combined
      deployment of a stent. Although stents are successful in the majority of cases, a
      large percentage of patients (20-30%) still suffer a second vessel lumen
      reduction known as in-stent restenosis. In-stent restenosis is recognized to be
      caused by the mechanical and foreign body challenges elicited by the device. Drug
      eluting stents have been recently made available to tackle restenosis, but their
      short clinical history and high costs may limit their future use. The present
      review links the most recent biologic findings related to in-stent restenosis to
      the devices' phyisico-chemical features in an attempt to demonstrate that a new
      generation of stents may be developed without the need of drug elution.

PMID- 16293083
TI  - Alternative bearing surfaces in total hip arthroplasty.
AB  - Total hip arthroplasty continues to be one of the most effective surgical
      procedures currently available. The longevity of this otherwise very successful
      procedure is compromised by the wear of the bearing surface. In recent years,
      great advances have been made in the design of bearing surfaces that poise to
      offer extended performance to these artificial joints. The purpose of this review
      is to discuss the recent technologic advances in bearing surfaces and offer an
      insight to the potential benefits and concerns with the alternative bearing
      surfaces.

PMID- 16293084
TI  - Implants for the first metatarsophalangeal joint and prospective considerations.
AB  - This article reviews the anatomy, pathology and biomechanics of the key joint of
      the foot, the first metatarsophalangeal joint, before focusing on the various
      designs of prosthesis that have been proposed for this joint. Metal
      hemiarthroplasties, single-piece, double-stem silicone implants and
      multicomponent implants are all considered in detail, as is an assessment of the
      available clinical results. In addition, preimplantation testing of the implants
      and the value of explant studies are discussed.

PMID- 16293085
TI  - Hydroxyapatite-coated external fixation pins.
AB  - The aim of this review is to report on studies of hydroxyapatite-coated external
      fixation pins as a solution to enhance pin fixation. In a highly loaded animal
      study, three tapered pin types were compared: Type A uncoated, Type B coated with
      hydroxyapatite and Type C coated with titanium. There was a 13-fold increase in
      the extraction torque of Type B pins compared with Type A, and a twofold increase
      compared with Type C pins. Extraction torque was significantly lower compared
      with the corresponding insertion torque in both Types A (p < 0.001) and C (p =
      0.003). Conversely, with the hydroxyapatite-coated pins there was no difference
      between extraction and insertion torque. In a clinical study of 76 external
      fixation pins in 19 patients treated with hemicallotasis for osteoarthritis on
      the medial side of the knee, pin insertion and extraction torque forces were
      measured. The patients were randomized to be treated with either standard tapered
      pins or tapered pins coated with hydroxyapatite. Extraction torque of the
      hydroxyapatite-coated pins was higher than the extraction torque of the standard
      pins in both cancellous and cortical bone (p < 0.005). In a prospective,
      randomized clinical study of osteoporotic wrist fractures, extraction torque of
      the coated pins was higher than with standard pins (p < 0.0001). These studies
      demonstrate that with the use of hydroxyapatite-coated pins, no deterioration of
      pin fixation occurs, and that there is no significant pin loosening and
      infection, regardless of bone type and loading conditions.

PMID- 16293086
TI  - Bioactive technologies for hemocompatibility.
AB  - The contact of any biomaterial with blood gives rise to multiple pathophysiologic
      defensive mechanisms such as activation of the coagulation cascade, platelet
      adhesion and activation of the complement system and leukocytes. The reduction of
      these events is of crucial importance for the successful clinical performance of
      a cardiovascular device. This can be achieved by improving the hemocompatibility
      of the device materials or by pharmacologic inhibition of the key enzymes
      responsible for the activation of the cascade reactions, or a combination of
      both. Different strategies have been developed during the last 20 years, and this
      article attempts to review the most significant, by dividing them into three main
      categories: bioinert or biopassive, biomimetic and bioactive strategies. With
      regard to bioactive strategies, particular attention is given to heparin
      immobilization and recent related technologies. References from both scientific
      literature and commercial sites are provided. Future development and studies are
      suggested.

PMID- 16293087
TI  - Molecular determinants of biocompatibility.
AB  - The biocompatibility of medical implants dictates the fate of almost all medical
      devices. It is well established that medical devices trigger a variety of adverse
      tissue responses, such as inflammation, fibrosis, infection and thrombosis.
      However, the mechanisms involved in biomaterial-mediated tissue responses remain
      largely unknown. The lack of such knowledge hinders the development of
      biomaterials with better biocompatibility and safety. The aim of this review is
      to summarize our current understanding of the processes governing foreign body
      reactions to tissue-contact devices. Obviously, this information is urgently
      needed for assisting the rational design of materials or medical devices to
      minimize undesirable tissue reactions upon implantation and, in addition, to
      promote the wound healing process.

PMID- 16293089
TI  - The daunting quest for a small diameter vascular graft.

PMID- 16293088
TI  - Stimuli-responsive polymers in gene delivery.
AB  - Recent interest in clinical therapy has been directed to deliver nucleic acids
      (DNA, RNA or short-chain oligonucleotides) that alter gene expression within a
      specific cell population, thereby manipulating cellular processes and responses,
      which in turn stimulate immune responses or tissue regeneration, or blocks
      expression at the level of transcription or translation for treatment of several
      diseases. Both ex vivo and in vivo gene delivery can be achieved mostly by using
      a delivery system (vector). Viral vectors exhibit high gene expression, but also
      have very significant side effects. Mainly cationic polymeric systems are used as
      nonviral vectors, although usually with low levels of transfection. Through the
      use of stimuli-responsive polymers as novel vectors for gene delivery, two
      benefits can be obtained: high gene expression efficiency and more selective gene
      expression.

PMID- 16293090
TI  - Noninvasive blood glucose test for diabetics.

PMID- 16293091
TI  - 19th European conference on biomaterials.

PMID- 16293092
TI  - Visual prosthetic device for bilateral end-stage macular degeneration.
AB  - Age-related macular degeneration is the leading cause of blindness in the USA.
      For the 1.8 million patients in the most advanced stages, there are currently no
      available treatments to improve vision. A visual prosthetic device that provides
      one eye with an enlarged retinal image of the central visual field has been
      developed with the goal of improving central vision in patients with bilateral
      end-stage macular degeneration. The other eye is left unimplanted to provide
      peripheral vision. This device is designed for implantation in the posterior
      chamber of the eye during an outpatient surgical procedure. In US Food and Drug
      Administration clinical trials, 72% of patients experienced an improvement in
      their level of visual impairment (profound or severe, to severe or moderate).
      This was accompanied by a clinically significant improvement in quality of life.

PMID- 16293094
TI  - Creating tissue microarrays by cutting-edge matrix assembly.
AB  - Tissue microarrays have become widely adopted for effective parallel in situ
      analysis of hundreds of tissues placed onto single slides. Traditionally, tissue
      core punches are transferred into predrilled holes within a scaffold block of
      paraffin or other material, and sectioned transversely by a microtome to generate
      array sections. While core-based arraying has greatly advanced tissue analyses,
      some of the limitations include restricted feature sizes and numbers, variable
      core depths of unpredictable tissue quality and inability to array thin-walled,
      stratified tissue samples such as intestines, vessels or skin. Overcoming these
      limitations, the authors have developed a practical arraying method that combines
      serial cutting and edge-to-edge bonding of samples to assemble a scaffold-free
      array matrix -- cutting-edge matrix assembly. Using cutting-edge matrix assembly,
      the authors have successfully placed more than 10,000 individual tissue pieces on
      a single histology glass slide. The potential biomedical utility and ongoing
      efforts to further develop the assembly technology and analysis of high-density
      cutting-edge matrix assembly tissue microarrays is discussed.

PMID- 16293093
TI  - Degradable, drug-eluting stents: a new frontier for the treatment of coronary
      artery disease.
AB  - This article reviews the clinical use of stents in the treatment of coronary
      artery disease and the rationale for the use of degradable, drug-eluting polymer
      stents. The authors note the challenges of using off-the-shelf polymers for the
      development of degradable stents, as well as the interplay between polymer
      properties and a functional stent design. Drug-eluting metal stents are the most
      significant advancement in the treatment of coronary artery disease, and have
      significantly reduced the occurrence of in-stent restenosis after placement. Some
      regard drug-eluting metal stents as the final technologic advancement in the
      treatment of coronary artery disease, others consider the future development of
      degradable, drug-eluting stents as the next logical step.

PMID- 16293095
TI  - Dialysis patients and cardiovascular problems: can technology solve the complex
      equation?
AB  - Patients with end-stage kidney disease undergoing chronic hemodialysis present
      higher mortality rates compared with the general population. Once patients are on
      hemodialysis, the risk of cardiovascular death is approximately 30-times higher
      than the general population, and still remains 10- to 20-times higher after
      stratification for age, gender and presence of diabetes. Approximately half of
      patient deaths on dialysis are attributed to cardiovascular causes, including
      coronary heart disease, cerebrovascular disease, peripheral vascular disease and
      heart failure. The cardiovascular burden of the hemodialysis patient arises from
      three different sources: risks inherent to the patient and the uremic syndrome,
      traditional risk factors and risk factors related to the dialysis therapy. Based
      on these considerations and the fact that several aspects of the dialysis
      procedure can cause either a cardiovascular burden or modify the burden already
      present, new technologies should be directed towards the approach of a possible
      'cardioprotective dialysis therapy'. This approach may significantly contribute
      new techniques and new dialysis machines. Born to make dialysis easy and safe,
      the new machines feature several options that make monitoring and online
      hemodiafiltration a simple routine. These and other features could make dialysis
      better tolerated and more efficient in protecting from fatal cardiovascular
      events.

PMID- 16293096
TI  - Ultrafiltration for acute decompensated heart failure.
AB  - For the 13th consecutive year, acute decompensated heart failure is the most
      common reason for admission to American hospitals. Most patients admitted for
      decompensated heart failure are by definition, diuretic resistant. The
      therapeutic objective in these patients is volume and sodium removal, and the
      restoration of diuretic sensitivity. In a significant proportion of patients,
      this objective is not met, subjecting patients to readmission for recurrent (or
      continued) heart failure decompensation. Ultrafiltration therapy offers the
      potential of greater volume and sodium removal as compared with conventional
      therapies in a more expeditious manner. Ultrafiltration can be accomplished
      safely, quickly and on a regular telemetry ward in extremely ill patients, but
      relies on earlier discharge with reduced readmission rates to be economically
      feasible.

PMID- 16293097
TI  - Central venous access devices in patients with hemophilia.
AB  - Hemophilia is a hereditary disorder in which the major clinical manifestation is
      bleeding into the joints, muscles, internal organs and the CNS, often without any
      obvious trauma. Bleeding can be fatal as in the case of CNS hemorrhage, or
      severely debilitating following repeated bleeding into joints that results in
      crippling arthritis. Treatment for hemophilia includes the intravenous
      administration of clotting factor concentrates to replace the missing or
      defective protein. Venous access is therefore critical to the treatment of
      hemophilia and the prevention of complications due to bleeding. According to the
      US Centers for Disease Control and Prevention, approximately half of patients
      less than 16 years of age and one-third of all patients with hemophilia receive
      regular prophylactic injections of clotting factor concentrates. Prophylaxis, or
      the regular scheduled administration of antihemophilic factor concentrate, is
      effective in preventing bleeding. Among those patients with severe disease, in
      the absence of prophylaxis, approximately 13 bleeds, including nine joint
      hemorrhages, occur annually. In contrast, when prophylaxis is administered, the
      annual number of total and joint bleeds decreases to five and three,
      respectively. One of the major barriers to the more wide-spread use of
      prophylaxis is venous access. While peripheral venipuncture remains the first
      choice for venous access, central venous access devices are frequently used to
      facilitate repeated and/or urgent administration of clotting factor concentrates.
      The advantages of central venous access devices are well recognized in certain
      treatment regimens such as prophylaxis and immune tolerance therapy, as well as
      certain patient groups such as young children in whom venipuncture is often
      difficult and traumatic, and adults with scarred veins. Central venous access
      devices also allow earlier commencement of both home treatment and prophylaxis.
      The goal of this review is to discuss the different types of central venous
      access devices and their role in the management of hemophilia to provide
      practitioners that care for patients with hemophilia with the necessary
      information to make sound therapeutic recommendations to their patients.

PMID- 16293098
TI  - Endoprevention of esophageal cancer: endoscopic ablation of Barrett's metaplasia
      and dysplasia.
AB  - This review describes the use of endoscopic therapy for the treatment of
      Barrett's disease and the prevention of esophageal carcinoma, predominantly a
      disease of older white men. While the term endoprevention may be novel,
      gastroenterologists have been using endoscopic techniques to prevent colon cancer
      for decades. For the endoprevention of Barrett's carcinoma, the regulatory
      approval for the use of porfimer sodium photodynamic therapy was an important
      milestone, as this treatment has been proven to safely ablate Barrett's glandular
      epithelium, including high-grade dysplasia, and significantly decrease the risk
      for the development of invasive cancer in several single-center studies, a
      prospective multicenter randomized controlled study using expert centralized
      histopathology analysis and long-term single-center results. Newer methods of
      mucosal ablation, such as the radiofrequency balloon, have been developed for the
      treatment of patients with Barrett's metaplasia or dysplasia. These newly
      developed techniques are able to treat large fields of glandular epithelium in a
      short treatment procedure using safe, effective, durable methods for the complete
      ablation of Barrett's metaplasia and low-grade dysplasia. These techniques may
      finally allow the interventional gastrointestinal endoscopist to prevent the
      development of esophageal carcinoma, just as colonoscopy with polypectomy has
      prevented colon cancer. However, it will be critically important to document the
      safety, durability and efficacy of these devices. Ultimately, the impact of
      successful Barrett's ablation on the incidence of Barrett's carcinoma, and the
      need for postablation surveillance endoscopy must be determined.

PMID- 16293099
TI  - Devices for hand-assisted laparoscopic surgery.
AB  - A number of tools have been introduced to make laparoscopy easier. Some, such as
      3D video systems, are interesting, and may add a modicum of benefit in some
      situations, but overall, have not had substantial impact. Others, such as robotic
      surgery, clearly have great potential, but are simply too expensive for
      widespread use. A few, such as the argon beam coagulator, are helpful only in
      particular situations. One technique has lived up to its billing and moreover,
      can be applied in almost any laparoscopic procedure, it is cost effective and
      actually does make laparoscopy easier. Hand-assisted laparoscopic surgery is a
      useful adjunct to the laparoscopic surgeon, and should be considered by all
      interested in this endeavor. This review summarizes the current hand-assistance
      devices and their use.

PMID- 16293100
TI  - Current and future developments in artificial muscles using electroactive
      polymers.
AB  - For decades, electroactive polymers received relatively little attention due to
      their limited actuation capability. However, in the last 15 years, a series of
      electroactive polymer materials have emerged that produce a significant shape or
      size change in response to electrical stimulation. These materials have the
      closest functional similarity to biologic muscles, enabling the engineering of
      novel capabilities that were, up until recently, impossible to achieve. Efforts
      are underway to address the many challenges that are hampering the practical
      application of these materials, and recent progress has already led to dramatic
      capability improvements. Various novel mechanisms and devices were demonstrated
      including robotic fish, catheter steering elements, robotic arms, miniature
      grippers, loudspeakers, active diaphragms, Braille display and dust-wipers. For
      developers of future medical devices, these materials are offering numerous
      advantages for their flexibility, fracture toughness and controllability, as well
      as low mass and low power requirements. This article provides a review of the
      current status, challenges and potential near-future applications of these
      materials.

PMID- 16293101
TI  - Recent advances in the design of titanium alloys for orthopedic applications.
AB  - To increase an orthopedic implant's lifetime, research trends have included the
      development of new titanium alloys made of nontoxic elements with suitable
      mechanical properties (low Young's modulus - high fatigue strength), good
      workability and corrosion resistance. In accordance with the background on
      titanium and metallic biomaterials, recent interesting developments in titanium
      based biomaterials are reported in this review, with a special emphasis on the
      design of new metastable beta-titanium alloys for orthopedic applications. In
      addition, as the concept of titanium alloys can now be regarded as relatively
      old, having emerged at the beginning of the 1980s, the author suggests some
      future directions that would permit the emergence of a new generation of titanium
      implants.

PMID- 16293102
TI  - Medical devices for the diagnosis and treatment of obstructive sleep apnea.
AB  - Obstructive sleep apnea is increasingly being recognized as a serious public
      health problem, and is characterized by repetitive, complete or partial closure
      of the upper airway during sleep, resulting in sleep fragmentation and oxygen
      desaturation. The key symptoms of obstructive sleep apnea are snoring, witnessed
      apneas, excessive daytime sleepiness and deficits in neurocognitive function,
      adversely impacting on quality of life. The last 10 years have seen a steady
      increase in evidence linking obstructive sleep apnea to long-term cardiovascular
      morbidity, including hypertension, myocardial infarction and stroke, and an
      increased risk of motor vehicle accidents. The discovery of continuous positive
      airway pressure treatment, and the resultant recognition of the high prevalence
      of snoring and obstructive sleep apnea, and their impact on health, has spawned a
      new and rapidly growing global industry. Whilst diagnostic technologic
      advancements have evolved relatively rapidly, many questions relating to the use
      of such devices in clinical practice remain unresolved. Similarly, on the
      therapeutic front, advances in continuous positive airway pressure technology
      have broadened the use of such treatment, although compliance remains an
      important impediment to widespread treatment of this common disorder. This has
      prompted a search for simpler treatment alternatives, ranging from surgical,
      medical and dental therapies, although none have matched the efficacy of
      continuous positive airway pressure. Advances in our understanding of the
      neurobiology of sleep and respiration herald the prospect of pharmacologic
      treatment in the longer term.

PMID- 16293103
TI  - Regulation of nitric oxide production in snail (Lymnaea stagnalis) defence cells:
      a role for PKC and ERK signalling pathways.
AB  - BACKGROUND INFORMATION: Nitric oxide (NO) is an important molecule in innate
      immune responses. In molluscs NO is produced by mobile defence cells called
      haemocytes; however, the molecular mechanisms that regulate NO production in
      these cells is poorly understood. The present study focused on the role of cell
      signalling pathways in NO production by primary haemocytes from the snail Lymnaea
      stagnalis. RESULTS: When haemocytes were challenged with PMA (10 microM) or the
      beta-1,3-glucan laminarin (10 mg/ml), an 8-fold and 4-fold increase in NO
      production were observed after 60 min respectively. Moreover, the NOS (NO
      synthase) inhibitors L-NAME (N(G)-nitro-L-arginine methyl ester) and L-NMMA (N(G)
      monomethyl-L-arginine) were found to block laminarin- and PMA-induced NO
      synthesis. Treatment of haemocytes with PMA or laminarin also increased the
      phosphorylation (activation) status of PKC (protein kinase C). When haemocytes
      were preincubated with PKC inhibitors (calphostin C or GF109203X) or inhibitors
      of the ERK (extracellular-signal-regulated kinase) pathway (PD98059 or U0126)
      prior to challenge, significant reductions in PKC and ERK phosphorylation and NO
      production were observed following exposure to laminarin or PMA. The greatest
      effect on NO production was seen with GF109203X and U0126, with PMA-induced NO
      production inhibited by 94% and 87% and laminarin-induced NO production by 50%
      and 91% respectively. CONCLUSIONS: These data suggest that ERK and PKC comprise
      part of the signalling machinery that regulates NOS activation and subsequent
      production of NO in molluscan haemocytes. To our knowledge, this is the first
      report that shows a role for these signalling proteins in the generation of NO in
      invertebrate defence cells.

PMID- 16293104
TI  - One-step on-column purification and refolding of a single-chain variable fragment
      (scFv) antibody against tumour necrosis factor alpha.
AB  - Single-chain variable fragment (scFv) is a low-molecular-mass recombinant
      antibody and is usually expressed as inclusion bodies in Escherichia coli. Highly
      efficient purification and refolding methods are required to provide enough
      active proteins for therapeutic or diagnostic use. In the present study, an anti
      TNFalpha (tumour necrosis factor alpha) scFv (TNF-scFv) was constructed and
      expressed in E. coli BL21(DE3) star as inclusion bodies, and a convenient
      procedure of one-step on-column purification and refolding was provided for it.
      Briefly, denatured TNF-scFv was firstly captured by immobilized metal (Ni)
      affinity chromatography, and then non-denaturing detergent (Triton X-100)
      containing and beta-cyclodextrin-containing solutions were loaded in turn on to
      the column to perform 'artificial chaperone-assisted refolding' after removing
      impurities. More than 77% of denatured TNF-scFv protein was refolded successfully
      with a purity of more than 95%. Activity assays showed that refolded TNF-scFv
      could bind to rhTNFalpha (recombinant human TNFalpha) specifically with high
      affinity. It could inhibit rhTNFalpha from binding to TNF receptors and
      neutralize the cytolytic activity of rhTNFalpha against L929 cells effectively. A
      conclusion was obtained that this refolding method is time-saving and suitable
      for industrial production. It may also be applicable to other scFvs or other
      recombinant proteins.

PMID- 16293105
TI  - Gene silencing of HIV chemokine receptors using ribozymes and single-stranded
      antisense RNA.
AB  - The chemokine receptors CXCR4 and CCR5 are required for HIV-1 to enter cells, and
      the progression of HIV-1 infection to AIDS involves a switch in the co-receptor
      usage of the virus from CCR5 to CXCR4. These receptors therefore make attractive
      candidates for therapeutic intervention, and we have investigated the silencing
      of their genes by using ribozymes and single-stranded antisense RNAs. In the
      present study, we demonstrate using ribozymes that a depletion of CXCR4 and CCR5
      mRNAs can be achieved simultaneously in human PBMCs (peripheral blood mononuclear
      cells), cells commonly used by the virus for infection and replication. Ribozyme
      activity leads to an inhibition of the cell-surface expression of both CCR5 and
      CXCR4, resulting in a significant inhibition of HIV-1 replication when PBMCs are
      challenged with the virus. In addition, we show that small single-stranded
      antisense RNAs can also be used to silence CCR5 and CXCR4 genes when delivered to
      PBMCs. This silencing is caused by selective degradation of receptor mRNAs.

PMID- 16293106
TI  - Bacterial enzymes that can deglycate glucose- and fructose-modified lysine.
AB  - Deglycating enzymes, i.e. enzymes that reverse the initial stage of the Maillard
      reaction between glucose and primary amines, are known to occur in mammalian,
      fungal and other eukaryotic and prokaryotic cells. In this issue of Biochemical
      Journal, Wiame et al. now report the existence of bacterial enzymes and an operon
      that control the metabolism and deglycation of glucoselysine 6-phosphate, i.e.
      the phosphorylated condensation product of fructose and epsilon-aminolysine. The
      discovery has broad implications for bacterial metabolism and possibly for the
      repair of protein damage by fructose.

PMID- 16293107
TI  - Computational modelling of the receptor-tyrosine-kinase-activated MAPK pathway.
AB  - The MAPK (mitogen-activated protein kinase) pathway is one of the most important
      and intensively studied signalling pathways. It is at the heart of a molecular
      signalling network that governs the growth, proliferation, differentiation and
      survival of many, if not all, cell types. It is de-regulated in various diseases,
      ranging from cancer to immunological, inflammatory and degenerative syndromes,
      and thus represents an important drug target. Over recent years, the
      computational or mathematical modelling of biological systems has become
      increasingly valuable, and there is now a wide variety of mathematical models of
      the MAPK pathway which have led to some novel insights and predictions as to how
      this system functions. In the present review we give an overview of the processes
      involved in modelling a biological system using the popular approach of ordinary
      differential equations. Focusing on the MAPK pathway, we introduce the features
      and functions of the pathway itself before comparing the available models and
      describing what new biological insights they have led to.

PMID- 16293108
TI  - Sigma-1 receptor as regulator of neuronal intracellular Ca2+: clinical and
      therapeutic relevance.
AB  - Preserving brain function and cognitive faculties during aging and psychiatric
      diseases (e.g. psychotic, anxiety and affective disorders, dementia) is essential
      for the self-reliance and quality of life of patients. Cognitive loss involves
      not only memory, but also motor function. The decrease of catecholaminergic and
      excitatory neurotransmissions, as well as of protein phosphorylation, have
      currently been identified as prominent biological markers of the above-mentioned
      diseases. Such deleterious biological events are well known to occur downstream
      of a progressive decline of intracellular Ca2+ signalling. This latter
      constitutes a key target for the neuronal plasticity that has also been reported
      during aging and psychiatric disorders. Most of the medicines used in psychiatry
      are active on the sigma-1 receptor. This membrane bound receptor is widely
      distributed in memory-associated cortical and motor-related brainstem areas,
      prompting the hypothesis that it might contribute to the pathophysiology of these
      behavioural brain diseases. The sigma-1 receptor is characterized by a unique
      mode of action by regulating both Ca2+ entry at the plasma membrane level (i.e.
      via potassium channels, voltage-sensitive Ca2+ channels) and Ca2+ mobilization
      from endoplasmic stores [i.e. via Ins(1,4,5)P3 receptors]. This review presents
      recent data supporting the notion that drugs acting via the endoplasmic reticulum
      coupled sigma-1 receptor might reverse these deleterious events by restoring both
      extra- and intra-cellular Ca(2+)-dependent neuronal responses.

PMID- 16293109
TI  - Trafficking mechanism of water channel aquaporin-2.
AB  - Targeted positioning of the water channel AQP2 (aquaporin-2) strictly regulates
      body water homoeostasis. Trafficking of AQP2 to the apical membrane is critical
      for the reabsorption of water in renal collecting ducts. In addition to the cAMP
      mediated effect of vasopressin on AQP2 trafficking to the apical membrane, other
      signalling cascades can also induce this sorting. Recently, AQP2-binding proteins
      which could regulate this trafficking have been discovered; SPA-1 (signal-induced
      proliferation-associated gene-1), a GAP (GTPase-activating protein) for Rap1, and
      the cytoskeletal protein actin. This review summarizes recent advances related to
      the trafficking mechanisms of AQP2.

PMID- 16293110
TI  - Once upon a time there was beta-catenin in cadherin-mediated signalling.
AB  - beta-Catenin was initially characterized as a protein interacting with the
      cadherin cytoplasmic tail and regulating cell-cell contacts and actin
      cytoskeleton interactions. Moreover, the gene coding for the Drosophila
      orthologue of beta-catenin, armadillo, was independently identified downstream of
      wingless in the segment-polarity signalling pathway. In fact, beta
      catenin/Armadillo turned out to be key mediators of the Wnt/Wingless pathways in
      vertebrates and invertebrates. beta-Catenin participates in both adhesion and
      signalling functions in a mutually exclusive manner; bound to cadherins at the
      plasma membrane or 'unbound' in cytosolic or nuclear complexes. This model had
      placed beta-catenin at the crossroads between cadherin and Wnt signalling,
      leading to the dogma of inhibition of beta-catenin signalling by cadherins.

PMID- 16293111
TI  - Comparative characterization and expression analysis of the four Old Yellow
      Enzyme homologues from Shewanella oneidensis indicate differences in
      physiological function.
AB  - Shewanella oneidensis contains four genes that encode proteins that have high
      sequence identity with yeast OYE (Old Yellow Enzyme, an NADPH oxidoreductase),
      the well-studied archetype of the OYE protein family. The present paper describes
      the first comparative study of OYEs that are present in a single bacterial
      species, performed to gain insight into their biochemical properties and
      physiological importance. The four proteins [named SYE1-SYE4 (Shewanella Yellow
      Enzyme 1-4)] were expressed as glutathione S-transferase fusion proteins in
      Escherichia coli. The yield of SYE2, however, was too low for further
      characterization, even after expression attempts in S. oneidensis. The SYE1, SYE3
      and SYE4 proteins were found to have characteristics similar to those of other
      OYE family members. They were identified as flavoproteins that catalyse the
      reduction of different alpha,beta-unsaturated carbonyl compounds and form charge
      transfer complexes with a range of phenolic compounds. Whereas the properties of
      SYE1 and SYE3 were very similar, those of SYE4 were clearly different in terms of
      ligand binding, catalytic efficiency and substrate specificity. Also, the
      activity of SYE4 was found to be NADPH-dependent, whereas SYE1 and SYE3 had a
      preference for NADH. It has been suggested that yeast OYE protects the actin
      cytoskeleton from oxidative stress. There are indications that bacterial OYEs are
      also involved in the oxidative stress response, but their exact role is unclear.
      Induction studies in S. oneidensis revealed that yeast and bacterial OYEs may
      share a common physiological role, i.e. the protection of cellular components
      against oxidative damage. As only SYE4 was induced under oxidative stress
      conditions, however, a functional divergence between bacterial OYEs is likely to
      exist.

PMID- 16293118
TI  - A chicken linkage map based on microsatellite markers genotyped on a Japanese
      Large Game and White Leghorn cross.
AB  - A detailed linkage map is necessary for efficient detection of quantitative trait
      loci (QTL) in chicken resource populations. In this study, microsatellite markers
      isolated from a (CA)n-enriched library (designated as ABR Markers) were mapped
      using a population developed from a cross between Japanese Game and White Leghorn
      chickens. In total, 296 markers including 193 ABR, 43 MCW, 31 ADL, 22 LEI, 3 HUJ,
      2 GCT, 1 UMA and 1 ROS were mapped by linkage to chicken chromosomes 1-14, 17-21,
      23, 24, 26-28 and Z. In addition, five markers were assigned to the map based on
      the chicken draft genomic sequence, bringing the total number of markers on the
      map to 301. The resulting linkage map will contribute to QTL mapping in chicken.

PMID- 16293119
TI  - Genetic mapping of quantitative trait loci affecting susceptibility in chicken to
      develop pulmonary hypertension syndrome.
AB  - Pulmonary hypertension syndrome (PHS), also referred to as ascites syndrome, is a
      growth-related disorder of chickens frequently observed in fast-growing broilers
      with insufficient pulmonary vascular capacity at low temperature and/or at high
      altitude. A cross between two genetically different broiler dam lines that
      originated from the White Plymouth Rock breed was used to produce a three
      generation population. This population was used for the detection and
      localization of quantitative trait loci (QTL) affecting PHS-related traits. Ten
      full-sib families consisting of 456 G2 birds were typed with 420 microsatellite
      markers covering 24 autosomal chromosomes. Phenotypic observations were collected
      on 4202 G3 birds and a full-sib across family regression interval mapping
      approach was used to identify QTL. There was statistical evidence for QTL on
      chicken chromosome 2 (GGA2), GGA4 and GGA6. Suggestive QTL were found on
      chromosomes 5, 8, 10, 27 and 28. The most significant QTL were located on GGA2
      for right and total ventricular weight as percentage of body weight (%RV and %TV
      respectively). A related trait, the ratio of right ventricular weight as
      percentage to total ventricular weight (RATIO), reached the suggestive threshold
      on this chromosome. All three QTL effects identified on GGA2 had their maximum
      test statistic in the region flanked by markers MCW0185 and MCW0245 (335-421 cM).

PMID- 16293120
TI  - SNP detection and genetic mapping of porcine genes encoding enzymes in hepatic
      metabolic pathways and evaluation of linkage with carcass traits.
AB  - We have previously identified and mapped porcine expressed sequence tags (ESTs)
      derived from genes that are preferentially expressed in liver. The aim of the
      present study was to identify single nucleotide polymorphisms (SNPs) in porcine
      genes encoding enzymes in hepatic metabolic pathways and use the SNPs for
      mapping. Furthermore, these genes, which are involved in utilization and
      partitioning of nutrients, were examined for their effects on carcass and meat
      quality traits by linkage analyses. In total, 100 ESTs were screened for SNPs by
      single strand conformation polymorphism analyses across a diverse panel of
      animals with a 36% success rate. Twelve of 36 polymorphic loci segregated in a
      three-generation Duroc x Berlin Miniature Pig (F2) resource population, the DUMI
      resource population, and were genetically mapped. Interval mapping of the
      corresponding chromosomes was performed to verify mapping of the genes within
      quantitative trait loci (QTL) regions detected in this resource population. QTL
      with genome-wide significance were detected in the vicinity of GNMT, ESTL147 and
      HGD. These loci therefore are positional candidate genes.

PMID- 16293121
TI  - Application of bovine microsatellite markers for genetic diversity analysis of
      Swiss yak (Poephagus grunniens).
AB  - In order to assess the applicability of bovine microsatellite markers for
      population genetic studies in Swiss yak, 131 bovine microsatellite markers were
      tested on a panel of 10 animals. Efficient amplification was observed for 124
      markers (94.6%) with a total of 476 alleles, of which 117 markers (94.3%) were
      polymorphic. The number of alleles per locus among the polymorphic markers ranged
      from two to nine. Seven loci (ILSTS005, BMS424B, BMS1825, BMS672, BM1314, ETH123
      and BM6017) failed to amplify yak genomic DNA. Two cattle Y-chromosome specific
      microsatellite markers (INRA126 and BM861) amplified genomic DNA from both male
      and female yaks. However, two additional markers on cattle Y-chromosome (INRA124
      and INRA189) amplified DNA from only males. Of the polymorphic markers, 24
      microsatellites proposed by CaDBase for within- and cross-species comparisons and
      two additional highly polymorphic markers (MHCII and TGLA73) were used to
      investigate the genetic variability and the population structure of a Swiss yak
      herd that included 51 additional animals. The polymorphic information content
      ranged from 0.355 to 0.752, while observed heterozygosity (HO) ranged from 0.348
      to 0.823. Furthermore, a set of 13 markers, organized into three multiplex
      polymerase chain reactions, was evaluated for routine parentage testing. This set
      provided an exclusion probability in a family of four yaks (both parents and two
      offspring) of 0.995. These microsatellites serve as useful tools for genetic
      characterization of the yak, which continues to be an important domestic
      livestock species.

PMID- 16293122
TI  - QTL mapping for teat number in an Iberian-by-Meishan pig intercross.
AB  - The aim of this study was to investigate chromosomal regions affecting the number
      of teats in pigs and possible epistatic interactions between the identified
      quantitative trait loci (QTL). An experimental F2 cross between Iberian and
      Chinese Meishan lines was used for this purpose. A genomic scan was conducted
      with 117 markers covering the 18 porcine autosomes. Linkage analyses were
      performed by interval mapping using an animal model to estimate QTL and additive
      polygenic effects. Complementary analyses with models fitting two QTL were also
      carried out. The results showed three genomewide significant QTL mapping on
      chromosomes 5, 10 and 12, whose joint action control up to 30% of the phenotypic
      variance of the trait. Meishan alleles had a positive additive effect on teat
      number, and a positive-additive x additive-epistatic interaction was detected
      between QTL on chromosomes 10 and 12.

PMID- 16293123
TI  - Characterization of the COMMD1 (MURR1) mutation causing copper toxicosis in
      Bedlington terriers.
AB  - Copper toxicosis is an autosomal recessive disorder affecting Bedlington
      terriers, characterized by elevated liver copper levels and early death of
      affected dogs. Genetic linkage mapping studies initially identified linkage
      between the disease and the microsatellite marker C04107. Subsequently, the
      deletion of exon 2 of the copper metabolism domain containing 1 (COMMD1) gene
      (formerly MURR1) was shown to be the major cause of copper toxicosis, although
      the deletion breakpoints were not defined. In this investigation, polymerase
      chain reaction (PCR)-based techniques and sequencing were used to isolate the
      deletion breakpoints, utilizing the newly available dog genome sequence. The
      breakpoints were positioned at 65.3091 and 65.3489 Mb of dog chromosome 10, in
      intron 1 and intron 2 of COMMD1 respectively, a deletion of 39.7 kb. The two
      breakpoints share sequence homology suggesting that homologous recombination may
      have been responsible for the deletion. Using this information, a genomic
      diagnostic test for the COMMD1 deletion was developed and compared with
      microsatellite C04107 genotypes of 40 Bedlington terriers. Results from the 40
      samples showed allele 2 of C04107 to be in linkage disequilibrium with the COMMD1
      deletion.

PMID- 16293124
TI  - Assignment of immune-related genes to the channel catfish, Ictalurus punctatus,
      genetic map.
AB  - Eighteen new genes, adenosine A1 receptor (ADORA1), complement component 4-beta
      (C4b), complement component 8-beta (C8b), chemokine ligand 19 (CCL19), chemokine
      ligand 21 (CCL21), chemokine ligand 25 (CCL25), chemokine receptor 2 (CCR2),
      chemokine receptor 5 (CCR5), chemokine receptor 4 (CCR4), chemokine receptor 7
      (CCR7), chemokine receptor 9 (CCR9), interleukin 1-beta (IL1B), integrin II-beta
      (ITGB2), novel immune type receptor 2 (NITR2), novel immune type receptor 4
      (NITR4), natural killer cell lysin (NKLYSIN), nucleotide excision repair (RAD23B)
      and tumour necrosis factor-alpha (TNF), were assigned to the channel catfish
      (Ictalurus punctatus) genetic linkage map. Polymorphic microsatellite markers
      were developed for NITR2, NITR4 and RAD23B from short-tandem repeats in the
      available sequence. Polymorphic microsatellite markers were developed for the
      remaining 15 genes by short-tandem repeat-anchored primer sequencing of catfish
      bacterial artificial chromosomes. Two gene clusters (MYOG-NRAMP-ADORA1) and (CCR4
      CCR2-CCR5) displayed conservation of synteny between catfish and mammals.
      Assignment of 18 new genes to the catfish linkage map will further advance
      integration of genetic and physical maps and comparative mapping between channel
      catfish and map rich species.

PMID- 16293125
TI  - Cytogenetic mapping of immunity-related genes in the domestic horse.
AB  - Chromosomal locations of 19 horse immunity-related loci (CASP1, CD14, EIF5A,
      FCER1A, IFNG, IL12A, IL12B, IL12RB2, IL1A, IL23A, IL4, IL6, MMP7, MS4A2, MYD88,
      NOS2A, PTGS2, TFRC and TLR2) were determined by fluorescence in situ
      hybridization. For IFNG and PTGS2, this study is a confirmation of their
      previously reported position. In addition, microsatellite (HMBr1) was localized
      in the same region as IFNG. All genes were assigned to regions of conserved
      synteny and the data obtained in this study enhance the comparative human-horse
      map. Cytogenetic localization of IL6 to ECA4q14-q21.1 suggested a new breakage
      point that changes the order of loci compared with HSA7. The map assignments of
      these loci serve as anchors for other loci and will aid in the search for
      candidate genes associated with traits in the horse.

PMID- 16293126
TI  - Radiation hybrid mapping of porcine CMYA2 and CMYA4.

PMID- 16293127
TI  - Radiation hybrid mapping of the porcine PPP2CA, PPP2CB, PPP2R1A and PPP2R1B
      genes.

PMID- 16293128
TI  - Sequences and mapping of genes encoding porcine tyrosinase (TYR) and tyrosinase
      related proteins (TYRP1 and TYRP2).

PMID- 16293129
TI  - Assignment of the phospholipase Cbeta1 (PLCB1) gene to porcine chromosome 17.

PMID- 16293130
TI  - The B-cell CLL lymphoma 2 (BCL2) gene maps to equine chromosome 8q22.

PMID- 16293132
TI  - A PCR-RFLP method for genotyping the myostatin locus in Piemontese cattle.

PMID- 16293131
TI  - SNP detection and association analyses of candidate genes for rupture of the
      cranial cruciate ligament in the dog.

PMID- 16293133
TI  - Assignment of porcine insulin-like growth factor-binding protein-4 (IGFBP4) to
      SSC12 by fluorescence in situ hybridization and radiation hybrid mapping.

PMID- 16293134
TI  - Assignments of the GAS6, POSTN and EFNB2 genes to SSC11 by somatic cell and
      radiation hybrid panels.

PMID- 16293135
TI  - Eight microsatellite loci for the Pacific oyster Crassostrea gigas.

PMID- 16293136
TI  - Molecular cloning, polymorphism and mapping of the porcine SFRS1 gene.

PMID- 16293137
TI  - Identification of two bovine microsatellite markers in a defined region of BTA6.

PMID- 16293138
TI  - Radiation hybrid mapping of five genes isolated from a porcine fetus skeletal
      muscle cDNA library.

PMID- 16293139
TI  - The canine CTSD gene as a candidate for late-onset neuronal ceroid
      lipofuscinosis.

PMID- 16293140
TI  - Assignment of 12 genes to porcine chromosome 1 by linkage and radiation hybrid
      mapping.

PMID- 16293141
TI  - TLR4 variation in Yellowstone bison.

PMID- 16293142
TI  - Construction and characterization of a BAC library for Carassius auratus gibelio,
      a gynogenetic polyploid fish.

PMID- 16293143
TI  - Radiation hybrid mapping of equine CDK2, DGKA, DNAJC14, MMP19, CTSL and GAS1.

PMID- 16293144
TI  - Genomic characterization and expression analysis of the baculoviral IAP repeat-
      containing 2 (BIRC2) gene in channel catfish, Ictalurus punctatus.

PMID- 16293145
TI  - Spider Lamb Syndrome (SLS) mutation frequency in German Suffolk sheep.

PMID- 16293146
TI  - Radiation hybrid mapping of 10 genes to porcine chromosomes.

PMID- 16293148
TI  - Challenging our understanding of the musculoskeletal system.

PMID- 16293149
TI  - Adaptation of muscle size and myofascial force transmission: a review and some
      new experimental results.
AB  - This paper considers the literature and some new experimental results important
      for adaptation of muscle fiber cross-sectional area and serial sarcomere number.
      Two major points emerge: (1) general rules for the regulation of adaptation (for
      in vivo immobilization, low gravity conditions, synergist ablation, tenotomy and
      retinaculum trans-section experiments) cannot be derived. As a consequence,
      paradoxes are reported in the literature. Some paradoxes are resolved by
      considering the interaction between different levels of organization (e.g. muscle
      geometrical effects), but others cannot. (2) An inventory of signal transduction
      pathways affecting rates of muscle protein synthesis and/or degradation reveals
      controversy concerning the pathways and their relative contributions. A major
      explanation for the above is not only the inherently limited control of the
      experimental conditions in vivo, but also of in situ experiments. Culturing of
      mature single Xenopus muscle fibers at high and low lengths (allowing
      longitudinal study of adaptation for periods up to 3 months) did not yield major
      changes in the fiber cross-sectional area or the serial sarcomere number. This is
      very different from substantial effects (within days) of immobilization in vivo.
      It is concluded that overall strain does not uniquely regulate muscle fiber size.
      Force transmission, via pathways other than the myotendinous junctions, may
      contribute to the discrepancies reported: because of substantial serial
      heterogeneity of sarcomere lengths within muscle fibers creating local variations
      in the mechanical stimuli for adaptation. For the single muscle fiber, mechanical
      signalling is quite different from the in vivo or in vitro condition. Removal of
      tensile and shear effects of neighboring tissues (even of antagonistic muscle)
      modifies or removes mechanical stimuli for adaptation. It is concluded that the
      study of adaptation of muscle size requires an integrative approach taking into
      account fundamental mechanisms of adaptation, as well as effects of higher levels
      of organization. More attention should be paid to adaptation of connective
      tissues within and surrounding the muscle and their effects on muscular
      properties.

PMID- 16293150
TI  - Strength at the extracellular matrix-muscle interface.
AB  - Mechanical force is generated within skeletal muscle cells by contraction of
      specialized myofibrillar proteins. This paper explores how the contractile force
      generated at the sarcomeres within an individual muscle fiber is transferred
      through the connective tissue to move the bones. The initial key point for
      transfer of the contractile force is the muscle cell membrane (sarcolemma) where
      force is transferred laterally to the basement membrane (specialized
      extracellular matrix rich in laminins) to be integrated within the connective
      tissue (rich in collagens) before transmission to the tendons. Connections
      between (1) key molecules outside the myofiber in the basement membrane to (2)
      molecules within the sarcolemma of the myofiber and (3) the internal cytoplasmic
      structures of the cytoskeleton and sarcomeres are evaluated. Disturbances to many
      components of this complex interactive system adversely affect skeletal muscle
      strength and integrity, and can result in severe muscle diseases. The mechanical
      aspects of these crucial linkages are discussed, with particular reference to
      defects in laminin-alpha2 and integrin-alpha7. Novel interventions to potentially
      increase muscle strength and reduce myofiber damage are mentioned, and these are
      also highly relevant to muscle diseases and aging muscle.

PMID- 16293151
TI  - Myotendinous alterations and effects of resistive loading in old age.
AB  - The loss of muscle mass associated with ageing only partly explains the observed
      decline in muscle strength. This paper provides evidence of the contribution of
      muscular, tendinous and neural alterations to muscle weakness in old age and
      discusses the complex interplay between the changes of the contractile tissue
      with those of the tendinous tissue in relation to the mechanical behavior of the
      muscle as a whole. Despite the considerable structural and functional
      alterations, the elderly musculoskeletal system displays remarkable adaptability
      to training in old age and many of these adverse effects may be substantially
      mitigated, if not reversed, by resistive loading. The interplay between these
      muscular and tendinous adaptations has an impact both on the length-force and
      force-velocity relationships of the muscle and is likely to affect the range of
      motion, rate of force development, maximum force development and speed of
      movement of the older individual.

PMID- 16293152
TI  - Muscle connective tissue content of endurance-trained and inactive individuals.
AB  - Although it is known that exercise exerts a positive regulatory effect on
      collagen synthesis, the effects of endurance training on muscle endomysial
      connective tissue in man are not so well documented. To investigate this, a
      single muscle biopsy was collected from two groups of volunteers - endurance
      trained sports participants and age-matched healthy untrained individuals.
      Endomysial staining intensity of types I, III and IV collagen was quantified by
      immunohistochemical staining and image analysis methods. Gelatinase activity in
      the endomysium was also quantified histochemically. Mean cycling VO2peak values
      of 53+/-6 (SD) and 32+/-8 mL/kg/min (P<0.01) were recorded for the trained and
      untrained groups, respectively. The staining intensity of types I, III and IV
      collagen and gelatinase activity in the trained group were not significantly
      different from the untrained group. However, when the data for all 11 volunteers
      were pooled, significant negative correlations were found for type III collagen
      staining intensity and capillary/fiber ratio; and for the relationship between
      type IV collagen staining intensity and VO2peak. These results suggest a negative
      association between aerobic capacity and the intensity of staining for types III
      and IV collagen in muscle endomysium.

PMID- 16293153
TI  - The effect of delayed-onset muscle soreness on stretch reflexes in human low back
      muscles.
AB  - The aim of the study was to investigate the effect of moderate delayed-onset
      muscle soreness (DOMS) on the short latency stretch reflex (SLR) and long latency
      stretch reflex (LLR) response i.e. electromyographic (EMG) onset latencies and
      EMG amplitudes in erector spinae (ES). Nine males with muscle soreness (DOMS
      group) were tested 24, 48 h, and 7 days post-exercise. Eight males (control
      group) were tested likewise. EMG was measured from ES bilaterally at the level of
      L3/L4. The SLR was elicited by mechanically tapping the ES at L3/L4, and the LLR
      was elicited by sudden loadings of the spine. Significant reductions in force
      during maximal voluntary contractions and range of motion, and a significant
      increase in muscle soreness (measured by pressure algometry) and subjective
      experience of soreness in the low back indicated DOMS 24, and 48 h post-exercise
      in the DOMS group. No changes were observed in the control group. The SLR and LLR
      response were unaffected by DOMS, i.e. no changes in EMG latencies and amplitudes
      were observed. In conclusion, despite changes in DOMS indicators, the reflex
      system protecting the stability of the lumbar spine is apparently capable of
      maintaining an appropriate triggering of SLR and LLR.

PMID- 16293154
TI  - The efficacy of ice massage in the treatment of exercise-induced muscle damage.
AB  - The purpose of this investigation was to, firstly, examine the effects of
      repeated applications of ice massage on the indirect markers associated with
      muscle damage using a within-subjects cross-over design and secondly, to examine
      how ice massage affects muscle function in both static and dynamic contractions
      following unaccustomed eccentric exercise. Twelve males performed damaging
      exercise on two separate occasions. The protocol consisted of three sets of 10
      maximal eccentric repetitions of the elbow flexors using isokinetic dynamometry.
      Subjects were randomly assigned to an ice massage group or placebo group and
      received treatments immediately post-exercise, 24 and 48 h post-exercise. Muscle
      function (maximal isometric, slow and fast isokinetic contractions), creatine
      kinase, myoglobin, muscle soreness, limb girth and range of motion were measured
      pre, immediately post, 24, 48, 72 and 96 h post-exercise. Significant time
      effects were observed for all dependent variables (P<0.05). There were no
      significant differences between treatments. Ice massage is ineffective in
      reducing the indirect markers associated with exercise-induced muscle damage and
      enhancing recovery of muscle function in male exercisers unaccustomed to
      eccentric biased exercise.

PMID- 16293155
TI  - The e-health revolution: competitive options for nurse practitioners as local
      providers.

PMID- 16293156
TI  - Ensuring clinical education outcomes: a call for reevaluation and reform.

PMID- 16293157
TI  - Planning your nursing business.

PMID- 16293158
TI  - 2004 AANP National Nurse Practitioner Sample Survey, Part II: nurse practitioner
      prescribing.

PMID- 16293159
TI  - A case study: identifying a new case of Wilson's disease.
AB  - PURPOSE: To present a case of Wilson's disease that presented with fatigue,
      nausea, abdominal pain, and splenomegaly. Patient information, diagnostic tests,
      etiology, anatomy and physiology, pathophysiology, assessment, signs and
      symptoms, diagnosis, medical treatment, nursing interventions, patient education,
      and research findings related to Wilson's disease are discussed. DATA SOURCES:
      Case study and scientific literature from Internet, journals, and medical
      textbooks. CONCLUSIONS: Wilson's disease is a hereditary, autosomal-recessive
      disease affecting copper excretion. As copper accumulates, signs and symptoms
      appear. Individuals often present with nonspecific findings, making diagnosis
      difficult. IMPLICATIONS FOR PRACTICE: This article reviews this rare but
      potentially devastating disease. Early diagnosis is vital to prevent copper
      accumulation leading to hepatic cirrhosis, basal ganglia degeneration, and
      irreversible organ damage.

PMID- 16293160
TI  - BRCA1 genetic mutation and its link to ovarian cancer: implications for advanced
      practice nurses.
AB  - PURPOSE: The purpose of this paper is to review (a) the linkage between the BRCA1
      gene and ovarian cancer and (b) BRCA1 testing and its related issues. This review
      is aimed for nurse practitioners (NPs), who may be in positions to identify those
      at risk for BRCA1-associated ovarian cancer and to assist patients with related
      issues. DATA SOURCES: Data sources include reviews and original research from
      scholarly journals and Internet sites. CONCLUSIONS: Ovarian cancer is a deadly
      disease. Identification of those at risk because of BRCA1 mutation is possible
      through genetic testing. Testing for BRCA1 gene mutations has many implications
      whether results are positive or negative. Those with positive results will be
      faced with decisions regarding the best management strategies. Negative results
      do not completely eliminate ovarian cancer risk. Current management options for
      carriers of the BRCA1 mutation include taking no action, increasing surveillance
      for ovarian cancer, and chemoprevention with oral contraceptives or prophylactic
      oophorectomy for those who have completed childbearing. It is essential that NPs
      have knowledge underlying the issues and concerns of patients and their families
      at risk for BRCA1-associated ovarian cancer. IMPLICATIONS FOR PRACTICE: NPs are
      in a unique position to help identify BRCA1 mutation carriers and to assist them
      and their families with the complex issues involving genetic testing and
      management options. Understanding these issues will allow NPs to give appropriate
      care that may include making appropriate referrals to certified genetic
      counselors and having balanced discussions on treatment options. Such
      measurements may improve early diagnosis of ovarian cancer and increase survival
      from this disease.

PMID- 16293161
TI  - Privacy concerns of patients and nurse practitioners in primary care--an APRNet
      study.
AB  - PURPOSE: This study explores and compares the privacy concerns of primary care
      nurse practitioners (NPs) and their patients. DATA SOURCES: Privacy concerns were
      identified in separate focus groups of NPs and patients, and then parallel survey
      instruments were designed and administered to 27 NPs and 185 of their patients.
      All subjects were recruited through APRNet, a regional practice-based research
      network of NPs in southern New England encompassing 58 practices. CONCLUSIONS:
      Both groups demonstrated high levels of concern regarding privacy. While NPs and
      patients had similar levels of concern about most issues, there were some notable
      differences regarding breeches because of carelessness, disclosures for research,
      and which disorders require the most care in maintaining privacy. IMPLICATIONS
      FOR PRACTICE: These results allow NPs to anticipate patient privacy concerns and
      to enhance trust in the clinical relationship. These results also indicate the
      need to educate patients regarding privacy rights and expectations.

PMID- 16293162
TI  - Central obesity, the metabolic syndrome, and plasminogen activator inhibitor-1 in
      young adults.
AB  - PURPOSE: To determine the association of central obesity with the components of
      the metabolic syndrome (i.e., hyperinsulinemia, hypertension,
      hypertriglyceridemia, low levels of high-density lipoprotein cholesterol [HDL-C])
      and plasma levels of plasminogen activator inhibitor-1 (PAI-1) in young adults.
      We hypothesized that central obesity as determined by waist circumference would
      be predictive of components of the metabolic syndrome and of PAI-1. DATA SOURCES:
      Participants in this descriptive study consisted of 85 healthy young adults aged
      19-22 years, 62% women who fasted for 12 h prior to data collection in the
      General Clinical Research Center at a major university hospital medical center in
      the southeastern United States. CONCLUSIONS: The majority of the participants had
      one or more components of the metabolic syndrome (n= 43, 51%). Central obesity
      was present in 14.1% and was more common in women than men (chi(2)= 5.11; p=
      0.021). Central obesity was significantly and positively correlated with elevated
      blood pressure (BP) and levels of insulin and PAI-1 while being negatively
      correlated with HDL-C. In multiple regression analyses, diastolic BP, insulin,
      and HDL-C were predictors of waist circumference (R(2)= 0.615). In a separate
      multiple regression, PAI-1 was predicted by waist circumference (R(2)= 0.331).
      IMPLICATIONS FOR PRACTICE: Many otherwise healthy young adults have one or more
      components of the metabolic syndrome. Assessment and institution of preventative
      measures for obesity and the components of the metabolic syndrome should begin in
      childhood. Furthermore, determination of waist circumference especially in young
      women may aid the practitioner to identify those at risk for the metabolic
      syndrome earlier in their disease trajectory. Furthermore, insulin resistance is
      believed to occur initially in the trajectory of the metabolic syndrome, making
      it a principal contender for suitable interventions to reduce risk for both type
      2 diabetes and cardiovascular disease (CVD). Homeostatic model assessment for
      insulin resistance was used to assess for insulin resistance among the euglycemic
      participants. Recording the presence of insulin resistance will aid the
      practitioner in determining if a low-risk patient is in peril for development of
      type 2 diabetes and/or CVD. Early cardiovascular risk recognition is vital to
      clinical practice as it allows more time for the practitioner to counsel patients
      for the essential planning needed to make lifestyle changes.

PMID- 16293163
TI  - The paradox of obesity in patients with heart failure.
AB  - PURPOSE: Heart failure (HF) patients often have comorbid conditions that confound
      management and adversely affect prognosis. The purpose of this study was to
      determine whether the obesity paradox is also present in hospitalized HF patients
      in an integrated healthcare system. DATA SOURCES: A cohort of 2707 patients with
      a primary diagnosis of HF was identified within an integrated, 20-hospital
      healthcare system. Patients were identified by ICD-9 codes or a left ventricular
      ejection fraction < or =40% dating back to 1995. Body mass index (BMI) was
      calculated using the first measured height and weight when hospitalized with HF.
      Survival rates were calculated using Kaplan Meier estimation. Hazard ratios for 3
      year mortality with 95% confidence intervals were assessed using Cox regression,
      controlling for age, gender, and severity of illness at time of diagnosis.
      CONCLUSIONS: Three-year survival rates paradoxically improved for patients with
      increasing BMI. Survival rates for the larger three BMI quartiles were
      significantly better than for the lowest quartile after adjusting for severity of
      illness, age, and gender. IMPLICATIONS FOR PRACTICE: While obesity increases the
      risk of developing HF approximately twofold, reports involving stable outpatients
      suggest that obesity is associated with improved survival after the development
      of HF. This finding is paradoxical because obesity increases the risk and worsens
      the prognosis of other cardiovascular diseases.

PMID- 16293165
TI  - Cornucopia of health--widening the contribution of museums, libraries and
      archives.

PMID- 16293164
TI  - Quality improvement and changes in diabetic patient outcomes in an academic nurse
      practitioner primary care practice.
AB  - PURPOSE: To examine a set of system interventions in the management of patients
      with diabetes and the outcomes of their care. DATA SOURCES: Preintervention and
      postintervention data collected from electronic medical records. CONCLUSIONS: The
      sample size was smaller than expected, contributing to a lack of statistical
      significance from preintervention to postintervention in the patient outcome
      measures. The systems-level variables that were under the direct control of the
      clinic staff (e.g., pneumococcal vaccine given) showed great improvement. In the
      preintervention period, the percentage of "yes" responses to the system-level
      variables ranged from 8 to 24 and jumped to 16 to 95 after the intervention.
      IMPLICATIONS FOR PRACTICE: Unequivocally, this project demonstrated that systems
      level changes result in improved care being provided to patients; however, these
      had minimal impact on the patient outcome variables. Promoting change in patient
      behavior is difficult, which may have contributed to the lack of significance in
      this area, while the variables under the direct control of the clinic staff were
      more easily changed.

PMID- 16293166
TI  - Availability of accessible publications: designing a methodology to provide
      reliable estimates for the Right to Read Alliance.
AB  - OBJECTIVES: To establish reliable estimates of the proportion of books available
      in formats accessible to visually impaired people; to recommend a practical
      method of updating the estimates. METHODS: The project had two stages. Stage one
      estimated the overall availability of all categories of books. The British
      National Bibliography (BNB) for 1999-2003 was chosen as the sampling frame. A
      sample of 2069 titles over the 5 years was selected using a systematic sample
      design. These titles were then checked for availability against the catalogues of
      four major producer/suppliers of materials in accessible formats. The second
      stage involved checking the availability of books in six genres; about 400 titles
      for each genre were examined. RESULTS: Of the titles selected for the overall
      estimate, 92 (4.4%) were found to be available in one or more accessible formats.
      Availability of titles in accessible formats varied greatly between categories.
      Adult fiction had the highest number of available publications (26.3%), least
      represented were cookery (1.9%) and gardening (1.8%). CONCLUSIONS: This study
      provided baseline figures and a methodology for the Right to Read Alliance to
      monitor their progress in campaigning for more books to be accessible to visually
      impaired people.

PMID- 16293167
TI  - Learning resource needs of UK NHS support staff.
AB  - BACKGROUND: A report on the findings of research into the learning resource needs
      of support staff conducted at York Hospital. METHODS: A qualitative method of
      focus groups was used to explore the views and experiences of support staff. This
      provided a rich source of data and allowed an often overlooked group to give
      their own experiences of learning and libraries. This was supplemented by one-to
      one interviews using more in-depth questions. A literacy and numeracy test gave a
      general picture of essential skill levels within the sample group. RESULTS: An
      improvement in communication to support staff needs to take place to ensure that
      all support staff know about the library, how and where to access training and
      obtain a network computer password. The project confirmed the need to expand
      library resources for support staff. It was found that there were no obvious
      essential skills resources within the Trust and a lack of awareness of essential
      skill issues. CONCLUSION: The learning needs of support staff need to be
      addressed sensitively. Many have had unfavourable experiences. Lack of access to
      computers and information technology (IT) training contributed to the group
      favouring written communication. More work needs to be done on essential skills
      for all staff.

PMID- 16293168
TI  - Access to learning resources for students on placement in the UK: what are the
      issues and how can we resolve them?
AB  - AIM: To compile a list of the issues regarding access to learning resources which
      affect students on placement in the UK and suggest some ways in which these can
      be resolved. RESULTS: Issues relating to PC access, network access, software,
      firewalls, disciplinary procedures, electronic information resources, virtual
      learning environments, service level agreements, physical access to libraries,
      book loans, reading lists and course committees are identified and discussed in
      relation to NHS libraries. CONCLUSIONS: Successful resolution of the IT and
      library issues, which are increasingly inter-linked, can help to ensure that
      students have a positive placement experience. Resolution will depend on close,
      regular liaison and can be assisted by negotiation of a clear Service Level
      Agreement.

PMID- 16293169
TI  - A survey of users and non-users of a UK teaching hospital library and information
      service.
AB  - BACKGROUND: The Lancashire Teaching Hospitals NHS Trust was formed in 2002 with
      the merger of two existing trusts. The library services unified to create a new
      expanded service with 11 staff. OBJECTIVES: The librarians wanted to test out
      users' opinions of the service, as a basis for a developmental strategy. They
      also wanted to find out to what extent they were offering a multi-disciplinary
      service, available to all staff. Therefore it was decided to include both users
      and non-users in the survey. METHODS: A twenty-question questionnaire was sent
      out to a 10% sample of registered users in all staff categories. The same
      questionnaire was sent out to a 10% sample of non-users, with the help of the
      Human Resources Department. RESULTS: The library staff and facilities were
      generally well regarded. The stock needed expansion in various areas, especially
      allied health and biomedical science. Non-users were in fact often occasional or
      remote users. Other non-users needed informing that they were entitled to use the
      service. CONCLUSIONS: Further research is required, especially concerning the
      information needs of allied health and scientific staff. There is a need for
      stock expansion. A marketing strategy is required to capture the interest of
      potential users.

PMID- 16293170
TI  - Health information in Italian public health websites: moving from inaccessibility
      to accessibility.
AB  - AIMS: In January 2004, the Italian government passed new legislation designed to
      give people with disabilities access to online services. Starting from the new
      legislation requirements, the purpose of this study is to investigate whether
      Italian Local Health Authorities websites are accessible to users with different
      abilities. METHODS: One hundred and seventy websites were analysed evaluating
      their compliance to the World Wide Web Consortium (W3C) Priority 1 guidelines via
      a combination of appropriate accessibility testing methods. This review was
      carried out twice: the first time it took place between the end of 2003 and May
      June 2004. The same survey was repeated again in December 2004, after the issuing
      of the draft of the Implementation Regulations for The Stanca Law in July 2004.
      In this second survey, all the websites analysed before were checked again to
      establish if some measures to make those sites accessible were taken. RESULTS:
      Seventy-six per cent of the analysed websites fail to satisfy the most basic W3C
      requirements, but Italian Local Health Authorities websites are likely to present
      significant improvements to access for some disabled user groups: the number of
      accessible websites increased consistently between the first and the second
      review. CONCLUSIONS: It seems that awareness of web accessibility issues is
      increasing among developers of health information websites because of law
      enforcement. Recommendations for future research and development are offered.

PMID- 16293171
TI  - Document delivery service at a Scottish primary care hospital library: Maria
      Henderson Library, Glasgow.

PMID- 16293172
TI  - How well are we doing in supporting evidence-based health care? The 'Information
      Mastery' perspective.

PMID- 16293173
TI  - Searching a biomedical bibliographic database from Hungary--the 'Magyar Orvosi
      Bibliografia'.

PMID- 16293174
TI  - Using research to justify your service: cause and effect.

PMID- 16293175
TI  - Supporting e-learning--a view from the Open University.

PMID- 16293178
TI  - WHO/EORTC classification of cutaneous lymphomas 2005: histological and molecular
      aspects.
AB  - The new WHO/EORTC classification for cutaneous lymphomas comprises mature T-cell
      and natural killer (NK)-cell neoplasms, mature B-cell neoplasms, and immature
      hematopoietic malignancies. It reflects the unique features of
      lymphoproliferative diseases of the skin, and at the same time it is as
      compatible as possible with the concepts underlying the WHO classification for
      nodal lymphomas and the EORTC classification of cutaneous lymphomas. This article
      reviews the histological, phenotypical, and molecular genetic features of the
      various nosological entities included in this new classification. These findings
      always have to be interpreted in the context of the clinical features and
      biologic behavior. AIM: To review the histological, phenotypical and molecular
      genetic features of the various nosological entities of the new WHO/EORTC
      classification for cutaneous lymphomas. METHODS: Extensive review of the
      literature cited in Medline and own data of the authors. RESULTS: The WHO/EORTC
      classification of cutaneous lymphomas comprises mature T-cell and NK-cell
      neoplasms, mature B-cell neoplasms and immature hematopoietic malignancies. It
      reflects the unique features of primary cutaneous lymphoproliferative diseases.
      CONCLUSION: This classification is as much as possible compatible with the
      concept of the WHO classification for nodal lymphomas and the EORTC
      classification of cutaneous lymphomas. The histological, phenotypical and
      molecular genetic features always have to be interpreted in the context of the
      clinical features and biologic behavior.

PMID- 16293179
TI  - Possible role of the bulge region in the pathogenesis of inflammatory scarring
      alopecia: lichen planopilaris as the prototype.
AB  - BACKGROUND: Lichen planopilaris (LPP) is the prototype of scarring alopecias that
      mainly target the infundibuloisthmic (bulge) region of hair follicle. Hair
      follicle stem cells have been shown to reside in the bulge. METHODS: We carried
      out this study to better define the possible pathogenetic role of the bulge in
      LPP. Thirty-five cases of LPP were studied. Multiple serial sections of biopsy
      specimens stained with hematoxylin and eosin, periodic acid Schiff-diastase, and
      Elastic van Gieson. The following immunostains were applied: CD3, CD4, CD8, CD1a,
      and Ki-67. Uninvolved follicles and normal scalp biopsy specimens served as
      normal controls. RESULTS: All cases showed a lichenoid lymphocytic infiltrate at
      the bulge region. The bulb area was spared. CD8(+) T cells were increased
      compared with CD4(+) T-cell population. Langerhans' cells were decreased.
      Proliferating stem cells, highlighted by Ki-67, showed a marked decrease in the
      bulge compared with uninvolved follicles. CONCLUSION: Our study supports the
      finding that in LPP, the inflammatory infiltrate mainly involves the bulge
      region, where the stem cells reside. Once this area is damaged, the hair loses
      its potential of regrowth with resulting scarring alopecia. This is in contrast
      with inflammatory non-scarring alopecias such as alopecia areata, where the bulb
      region is targeted, sparing the stem cells.

PMID- 16293180
TI  - hTERT expression in melanocytic lesions: an immunohistochemical study on paraffin
      embedded tissue.
AB  - BACKGROUND: Telomerase plays a role in the immortalization of cells and
      carcinogenesis. Previous studies have yielded conflicting results on whether
      human telomerase RNA (hTER) expression differs in nevi, atypical nevi and
      melanomas using polymerase chain reaction-based telomeric repeat amplification
      protocol or in situ hybridization assays. The aim of this study was to evaluate
      human telomerase reverse transcriptase (hTERT) staining in melanocytic lesions on
      paraffin-embedded tissues. METHODS: Paraffin-embedded sections from 12 acquired
      nevi, seven dysplastic nevi, 11 Spitz nevi, eight primary invasive melanomas, and
      three metastatic melanomas were studied for staining intensity (0-3+) and
      percentage of labeled cells with anti-hTERT. RESULTS: hTERT staining was observed
      in most cells (>75%), in all but three lesions, and was of greater intensity in
      the nucleus, especially the nucleolus, compared with the cytoplasm. Spitz nevi
      tended to have weaker hTERT staining (mean = 1.7) compared with acquired nevi
      (mean = 2.2), dysplastic nevi (mean = 2.4), primary melanomas (mean = 2.4), or
      metastatic melanomas (mean = 3). CONCLUSIONS: Although telomerase activity was
      weaker in Spitz nevi, there was overlap with other nevi and primary invasive
      melanomas in our small series. Thus, hTERT expression does not appear to be a
      reliable adjunct to the histological diagnosis of primary melanocytic lesions.

PMID- 16293182
TI  - Cutaneous extrarenal rhabdoid tumor with myogenic differentiation.
AB  - BACKGROUND: The rhabdoid phenotype is characterized by large epithelioid cells
      with abundant eosinophilic cytoplasm and paranuclear inclusions of intermediate
      filaments. Although originally described in tumors from pediatric kidneys, the
      rhabdoid phenotype has since been described in a variety of patient ages and
      extrarenal sites. Extraordinarily, the rhabdoid phenotype has emerged in
      cutaneous neoplasms, either as a pure extrarenal rhabdoid tumor or a composite
      phenotype coupled with another malignancy. Regardless of the clinical setting,
      the rhabdoid phenotype is uniformly associated with aggressive biological
      behavior. We report the findings from a rare and very aggressive primary
      extrarenal rhabdoid tumor of the skin with myogenic differentiation. CASE REPORT:
      A 53-year-old woman presented with an ulcerated nodule on her right medial calf
      and ipsilateral inguinal lymphadenopathy. Histological examination of the skin
      nodule as well as cytologic examination of a lymph node disclosed the
      characteristic rhabdoid phenotype. Electron microscopy demonstrated paranuclear
      globules of intermediate filaments; special stains suggested an underlying
      myogenic histogenesis. The patient was aggressively treated with chemotherapy but
      ultimately died of her disease 8 months after presentation. CONCLUSIONS: The
      rhabdoid phenotype is rarely seen in cutaneous neoplasms, but when present,
      portends a poor prognosis adding particular importance to its recognition.

PMID- 16293181
TI  - CD34 expression in primary cutaneous malignant melanoma: apropos of a case and
      review of the aberrant melanoma phenotype.
AB  - BACKGROUND: The histological diagnosis of malignant melanoma can be challenging.
      Immunohistochemical techniques may define a critical role in certain cases,
      specifically in establishing a primary diagnosis of melanoma. CD34 is a
      hemopoietic stem cell antigen expressed in bone marrow and endothelial cells, and
      may also be expressed in vascular and spindle cell tumors; it is generally
      negative in malignant melanoma. CASE REPORT: An 83-year-old white female
      presented with a 3-4 mm area on her right upper back, which had been present for
      several years. Histologic sections showed a polypoid distortion by sheets and
      nodules of transformed amelanotic melanocytes lying in intimate apposition to an
      attenuated epidermis without a concomitant radial growth phase. Tumor cells were
      extensively S-100 and CD34 positive and showed focal immunoreactivity with melan
      A and HMB-45. DISCUSSIONS: We present a case of malignant melanoma of nodular
      subtype, which strongly expressed CD34. The spectrum of abnormal phenotypes in
      malignant melanoma is reviewed, and a possible explanation for the presence of
      CD34 is discussed. This case demonstrates the potential of malignant melanoma to
      express CD34, defining an infrequently recognized aberrant phenotype. Whether or
      not expression of this marker is associated with a more aggressive clinical
      course remains to be determined.

PMID- 16293183
TI  - Ossified soft tissue leiomyoma in a patient with sickle cell anemia.
AB  - Osseous metaplasia in leiomyomas is extremely rare. Here, we report the case of
      an ossified subcutaneous leiomyoma in a 34-year-old African American man with
      sickle cell thalassemia who presented with a painful nodule of the scapular
      region, which appeared as a heavily mineralized soft tissue mass on chest
      radiographs. Histopathologic and immunohistochemical examination of the resected
      nodule revealed a benign soft tissue leiomyoma composed of intersecting fascicles
      of spindle cells that strongly expressed smooth muscle actin and caldesmon.
      Extensive intratumoral calcification and ossification were noticed. Only eight
      cases of ossified leiomyoma have been reported, of which two arose in the deep
      soft tissue.

PMID- 16293184
TI  - Markers of high-risk cutaneous melanoma: is there a winning combination for
      individualized prognosis?

PMID- 16293185
TI  - Membrane testosterone binding sites in prostate carcinoma as a potential new
      marker and therapeutic target: study in paraffin tissue sections.
AB  - BACKGROUND: Steroid action is mediated, in addition to classical intracellular
      receptors, by recently identified membrane sites, that generate rapid non-genomic
      effects. We have recently identified a membrane androgen receptor site on
      prostate carcinoma cells, mediating testosterone rapid effects on the
      cytoskeleton and secretion within minutes. METHODS: The aim of this study was to
      investigate whether membrane androgen receptors are differentially expressed in
      prostate carcinomas, and their relationship to the tumor grade. We examined the
      expression of membrane androgen receptors in archival material of 109 prostate
      carcinomas and 103 benign prostate hyperplasias, using fluorescein-labeled BSA
      coupled testosterone. RESULTS: We report that membrane androgen receptors are
      preferentially expressed in prostate carcinomas, and they correlate to their
      grade using the Gleason's microscopic grading score system. CONCLUSION: We
      conclude that membrane androgen receptors may represent an index of tumor
      aggressiveness and possibly specific targets for new therapeutic regimens.

PMID- 16293186
TI  - Local treatment in unresectable hepatic metastases of carcinoid tumors:
      Experiences with hepatic artery embolization and radiofrequency ablation.
AB  - BACKGROUND: Hepatic metastases of carcinoid tumors cause incapacitating symptoms,
      but are usually diffuse and therefore unresectable. In this article we evaluate
      our experiences with local treatment techniques in the management of carcinoid
      patients with hepatic metastases and failing systemic treatment. METHODS: Fifteen
      consecutive carcinoid patients (11 men and 4 women; median age 60 years; range 45
      71 years) were treated with either hepatic artery embolization (HAE) with Ivalon
      particles or radiofrequency ablation (RFA) (percutaneously or intra-operatively).
      Follow-up evaluation was performed by CT scan and 24-hours urinary 5-HIAA
      excretions. RESULTS: A total of 18 HAE's was performed in 13 patients, while 10
      lesions in 3 patients were treated with RFA. Median follow-up was 12.5 months (2 
      25 months). Median duration of symptoms was 22 months (8 - 193 months). Median
      overall decrease of 5-HIAA excretion 2 months after HAE was 32% with tumor
      regression on CT-scan in 4 patients (30%) and improvement of symptoms with a
      median duration of 15 months in 3 of them (23%). Embolization led to fatal
      hepatic failure in one patient. The 3 patients treated with RFA showed a decrease
      of urinary 5-HIAA values of 34, 81 and 93% respectively, with tumor regression in
      all of them. Improvement of symptoms was reported in 2 patients up to 25 months.
      CONCLUSION: Liver embolization performed late in the clinical course had limited
      effect on symptoms and biochemical and radiological parameters. First experiences
      with RFA are favorable and might encourage to apply RFA more widely in metastatic
      carcinoid.

PMID- 16293188
TI  - Memory and selective learning in children with spina bifida-myelomeningocele and
      shunted hydrocephalus: a preliminary study.
AB  - BACKGROUND: Selective learning is the ability to select items of relevance from
      among less important items. Limited evidence exists regarding the efficiency with
      which children with spina bifida-myelomeningocele and shunted hydrocephalus
      (SB/SH) are able to learn information. This report describes initial data related
      to components of learning and metacognitive skills in children with SB/SH.
      METHODS: Twenty six children with SB/SH and 26 controls (age: 7-16 y) with
      average intelligence, and monolingual English-speaking backgrounds participated
      in the study. Exclusion criteria for the SB/SH group were: prior history of shunt
      infection, history of seizure or shunt malfunction within the previous three
      months, prior diagnoses of attention disorders and/or clinical depression.
      Children were presented lists of words with equal exemplars each of two distinct
      semantic categories (e.g. fruits, animals), and told to make as high a score as
      possible by learning the words. The value of the words was designated by category
      membership (e.g. animals = low value; fruits = high value). The total number of
      words learned across three learning trials was used to determine memory span.
      Selective learning efficiency (SLE) was computed as the efficiency with which
      items of greater value were selectively learned across three trials. RESULTS:
      Children with SB/SH did worse than controls on memory span (P < 0.05). Although
      SLE was not significantly different between groups, when asked what strategy was
      used in the selective learning tasks, 65% of the SB/SH children said they tried
      to remember all words (inefficient strategy). In contrast, 85% of controls said
      they tried to remember the higher value words--the more efficient strategy.
      CONCLUSION: Success in school is often dependent on the ability to recall
      important facts selectively and ignore less important information. Children with
      SB/SH in our study had a poor memory span and were unable to monitor and report
      an efficient and workable metacognitive strategy required to remember a list of
      words. Preliminary findings may begin to explain our previous clinical and
      research findings wherein children with SB/SH often focus on extraneous details,
      but demonstrate difficulty remembering the main gist of a story/event.

PMID- 16293187
TI  - The Enhancer of split and Achaete-Scute complexes of Drosophilids derived from
      simple ur-complexes preserved in mosquito and honeybee.
AB  - BACKGROUND: In Drosophila melanogaster the Enhancer of split-Complex [E(spl)-C]
      consists of seven highly related genes encoding basic helix-loop-helix (bHLH)
      repressors and intermingled, four genes that belong to the Bearded (Brd) family.
      Both gene classes are targets of the Notch signalling pathway. The Achaete-Scute
      Complex [AS-C] comprises four genes encoding bHLH activators. The question arose
      how these complexes evolved with regard to gene number in the evolution of
      insects concentrating on Diptera and the Hymenoptera Apis mellifera. RESULTS: In
      Drosophilids both gene complexes are highly conserved, spanning roughly 40
      million years of evolution. However, in species more diverged like Anopheles or
      Apis we find dramatic differences. Here, the E(spl)-C consists of one bHLH
      (mbeta) and one Brd family member (malpha) in a head to head arrangement.
      Interestingly in Apis but not in Anopheles, there are two more E(spl) bHLH like
      genes within 250 kb, which may reflect duplication events in the honeybee that
      occurred independently of that in Diptera. The AS-C may have arisen from a single
      sc/l'sc like gene which is well conserved in Apis and Anopheles and a second ase
      like gene that is highly diverged, however, located within 50 kb. CONCLUSION:
      E(spl)-C and AS-C presumably evolved by gene duplication to the nowadays complex
      composition in Drosophilids in order to govern the accurate expression patterns
      typical for these highly evolved insects. The ancestral ur-complexes, however,
      consisted most likely of just two genes: E(spl)-C contains one bHLH member of
      mbeta type and one Brd family member of malpha type and AS-C contains one sc/l'sc
      and a highly diverged ase like gene.

PMID- 16293189
TI  - Abnormal expression and processing of the proprotein convertases PC1 and PC2 in
      human colorectal liver metastases.
AB  - BACKGROUND: The family of proprotein convertases has been recently implicated in
      tumorigenesis and metastasis in animal models. However, these studies have not
      yet been completely corroborated in human tumors. METHODS: Using RT PCR,
      immunoblot and immunohistochemistry we assessed the presence and the processing
      patterns of the convertases PC1 and PC2 as well as the PC2 specific chaperone 7B2
      in human liver metastases originating from colorectal cancer and compared them to
      unaffected and normal liver. Furthermore, we assessed the presence and processing
      profiles of PC1, PC2 and 7B2 in primary colon cancers. RESULTS: mRNA, protein
      expression, and protein cleavage profiles of proprotein convertases 1 and 2 are
      altered in liver colorectal metastasis, compared to unaffected and normal liver.
      Active PC1 protein is overexpressed in tumor, correlating with its mRNA profile.
      Moreover, the enhanced PC2 processing pattern in tumor correlates with the
      overexpression of its specific binding protein 7B2. These results were
      corroborated by immunohistochemistry. The specific and uniform convertase pattern
      observed in the metastases was present only in a fraction of primary colon
      cancers. CONCLUSION: The uniformly altered proprotein convertase profile in liver
      metastases is observed only in a fraction of primary colon cancers, suggesting
      possible selection processes involving PCs during metastasis as well as an active
      role of PCs in liver metastasis. In addition, the exclusive presence of 7B2 in
      metastatic tumors may represent a new target for early diagnosis, prognosis
      and/or treatment.

PMID- 16293190
TI  - Acquired homotypic and heterotypic immunity against oculogenital Chlamydia
      trachomatis serovars following female genital tract infection in mice.
AB  - BACKGROUND: Chlamydia trachomatis is the most common sexually transmitted
      bacterial pathogen causing female genital tract infection throughout the world.
      Reinfection with the same serovar, as well as multiple infections with different
      serovars, occurs in humans. Using a murine model of female C. trachomatis genital
      tract infection, we determined if homotypic and/or heterotypic protection against
      reinfection was induced following infection with human oculogenital strains of C.
      trachomatis belonging to two serovars (D and H) that have been shown to vary
      significantly in the course of infection in the murine model. METHODS: Groups of
      outbred CF-1 mice were reinfected intravaginally with a strain of either serovar
      D or H, two months after initial infection with these strains. Cellular immune
      and serologic status, both quantitative and qualitative, was assessed following
      initial infection, and the course of infection was monitored by culturing vaginal
      samples collected every 2-7 days following reinfection. RESULTS: Serovar D was
      both more virulent (longer duration of infection) and immunogenic (higher level
      of circulating and vaginal IgG and higher incidence of IgA in vaginal secretions)
      in the mouse genital tract. Although both serovars induced cross-reacting
      antibodies during the course of primary infection, prior infection with serovar H
      resulted in only a slight reduction in the median duration of infection against
      homotypic reinfection (p approximately 0.10), while prior infection with serovar
      D resulted in significant reduction in the median duration of infection against
      both homotypic (p < 0.01) and heterotypic reinfection (p < 0.01) when compared to
      primary infection in age and conditions matched controls. CONCLUSION: Serovar D
      infection resulted in significant homotypic and heterotypic protection against
      reinfection, while primary infection with serovar H resulted in only slight
      homotypic protection. In addition to being the first demonstration of acquired
      heterotypic immunity between human oculogenital serovars, the differences in the
      level and extent of this immunity could in part explain the stable difference in
      serovar prevalence among human isolates.

PMID- 16293191
TI  - Ancestral sequence alignment under optimal conditions.
AB  - BACKGROUND: Multiple genome alignment is an important problem in bioinformatics.
      An important subproblem used by many multiple alignment approaches is that of
      aligning two multiple alignments. Many popular alignment algorithms for DNA use
      the sum-of-pairs heuristic, where the score of a multiple alignment is the sum of
      its induced pairwise alignment scores. However, the biological meaning of the sum
      of-pairs of pairs heuristic is not obvious. Additionally, many algorithms based
      on the sum-of-pairs heuristic are complicated and slow, compared to pairwise
      alignment algorithms. An alternative approach to aligning alignments is to first
      infer ancestral sequences for each alignment, and then align the two ancestral
      sequences. In addition to being fast, this method has a clear biological basis
      that takes into account the evolution implied by an underlying phylogenetic tree.
      In this study we explore the accuracy of aligning alignments by ancestral
      sequence alignment. We examine the use of both maximum likelihood and parsimony
      to infer ancestral sequences. Additionally, we investigate the effect on accuracy
      of allowing ambiguity in our ancestral sequences. RESULTS: We use synthetic
      sequence data that we generate by simulating evolution on a phylogenetic tree. We
      use two different types of phylogenetic trees: trees with a period of rapid
      growth followed by a period of slow growth, and trees with a period of slow
      growth followed by a period of rapid growth. We examine the alignment accuracy of
      four ancestral sequence reconstruction and alignment methods: parsimony, maximum
      likelihood, ambiguous parsimony, and ambiguous maximum likelihood. Additionally,
      we compare against the alignment accuracy of two sum-of-pairs algorithms:
      ClustalW and the heuristic of Ma, Zhang, and Wang. CONCLUSION: We find that
      allowing ambiguity in ancestral sequences does not lead to better multiple
      alignments. Regardless of whether we use parsimony or maximum likelihood, the
      success of aligning ancestral sequences containing ambiguity is very sensitive to
      the choice of gap open cost. Surprisingly, we find that using maximum likelihood
      to infer ancestral sequences results in less accurate alignments than when using
      parsimony to infer ancestral sequences. Finally, we find that the sum-of-pairs
      methods produce better alignments than all of the ancestral alignment methods.

PMID- 16293192
TI  - Evaluation of potential reference genes in real-time RT-PCR studies of Atlantic
      salmon.
AB  - BACKGROUND: Salmonid fishes are among the most widely studied model fish species
      but reports on systematic evaluation of reference genes in qRT-PCR studies is
      lacking. RESULTS: The stability of six potential reference genes was examined in
      eight tissues of Atlantic salmon (Salmo salar), to determine the most suitable
      genes to be used in quantitative real-time RT-PCR analyses. The relative
      transcription levels of genes encoding 18S rRNA, S20 ribosomal protein, beta
      actin, glyceraldehyde-3P-dehydrogenase (GAPDH), and two paralog genes encoding
      elongation factor 1A (EF1AA and EF1AB) were quantified in gills, liver, head
      kidney, spleen, thymus, brain, muscle, and posterior intestine in six untreated
      adult fish, in addition to a group of individuals that went through
      smoltification. Based on calculations performed with the geNorm VBA applet, which
      determines the most stable genes from a set of tested genes in a given cDNA
      sample, the ranking of the examined genes in adult Atlantic salmon was
      EF1AB>EF1AA>beta-actin>18S rRNA>S20>GAPDH. When the same calculations were done
      on a total of 24 individuals from four stages in the smoltification process
      (presmolt, smolt, smoltified seawater and desmoltified freshwater), the gene
      ranking was EF1AB>EF1AA>S20>beta-actin>18S rRNA>GAPDH. CONCLUSION: Overall, this
      work suggests that the EF1AA and EF1AB genes can be useful as reference genes in
      qRT-PCR examination of gene expression in the Atlantic salmon.

PMID- 16293193
TI  - Inhibition of HIV derived lentiviral production by TAR RNA binding domain of TAT
      protein.
AB  - BACKGROUND: A critical step in the production of new HIV virions involves the TAT
      protein binding to the TAR element. The TAT protein contains in close proximity
      its TAR RNA binding domain and protein transduction domain (PTD). The PTD domain
      of TAT has been identified as being instrumental in the protein's ability to
      cross mammalian cell and nuclear membranes. All together, this information led us
      to form the hypothesis that a protein containing the TAR RNA binding domain could
      compete with the native full length TAT protein and effectively block the TAR RNA
      binding site in transduced HIV infected cells. RESULTS: We synthesized a short
      peptide named Tat-P, which contained the TAR RNA binding and PTD domains to
      examine whether the peptide has the potential of inhibiting TAT dependent HIV
      replication. We investigated the inhibiting effects of Tat-P in vitro using a HIV
      derived lentiviral vector model. We found that the TAT PTD domain not only
      efficiently transduced test cells, but also effectively inhibited the production
      of lentiviral particles in a TAT dependent manner. These results were also
      supported by data derived from the TAT activated LTR-luciferase expression model
      and RNA binding assays. CONCLUSION: Tat-P may become part of a category of anti
      HIV drugs that competes with full length TAT proteins to inhibit HIV replication.
      In addition, this study indicates that the HIV derived lentiviral vector system
      is a safe and reliable screening method for anti-HIV drugs, especially for those
      targeting the interaction of TAT and TAR RNAs.

PMID- 16293195
TI  - A 6-months assessment of the alcohol-related clinical burden at emergency rooms
      (ERs) in 11 acute care hospitals of an urban area in Germany.
AB  - BACKGROUND: The purpose of the study was to identify and to profile alcohol
      related attendances to emergency rooms (ERs) of 11 hospitals of various medical
      specialties covering a large urban population, to assess risk factors associated
      with short-stay cases, repeat attendances and higher degree of alcohol
      consumption and to estimate their impact on the alcohol-related burden at ERs.
      METHODS: A 6-months study was carried out to obtain clinical and administrative
      data on single and multiple attendances at ERs in 11 governmental acute hospitals
      in a large city in Germany. All alcohol-related attendances at ERs of study
      hospitals were eligible. A broad definition of alcohol-related attendances
      independently from alcohol diagnosis and various demographic, clinical and
      administrative measures were used. Odds ratios for the associations of these
      measures with duration of stay, repeat attendances and higher degrees of alcohol
      consumption were derived from multivariate binomial and multinomial logistic
      regression models. RESULTS: 1,748 patients with symptoms of alcohol consumption
      or withdrawal (inclusion rate 83.8%) yielded 2,372 attendances (3% of all medical
      admissions), and resulted in 12,629 inpatient-days. These patients accounted for
      10.7 cases per 1,000 inhabitants. The average duration of inpatient stay was 10
      days. 1,451 of all patients (83%) presented once, whereas the median of repeat
      attendances was three for the remaining 297 patients. Short-stay cases (<24
      hours) were significantly linked with male gender, alcohol misuse, trauma (or
      suspicion of a trauma) and medical specialties. Increased levels of alcohol
      consumption at first attendance were significantly associated with repeat
      attendances in due course. In a multinomial logistic regression model higher
      degrees of alcohol consumption were significantly associated with male gender,
      trauma, short-stays, attendance outside regular working time, and with repeat
      attendances and self-discharge. CONCLUSION: Apart from demographic factors, the
      alcohol-related clinical burden is largely determined by short-stay cases, repeat
      attendances and cases with higher levels of alcohol consumption at first
      attendance varying across medical specialties. These findings could be relevant
      for the planning of anti-alcoholic interventions at ERs.

PMID- 16293196
TI  - Environmental constraints on life histories in Antarctic ecosystems: tempos,
      timings and predictability.
AB  - Knowledge of Antarctic biotas and environments has increased dramatically in
      recent years. There has also been a rapid increase in the use of novel
      technologies. Despite this, some fundamental aspects of environmental control
      that structure physiological, ecological and life-history traits in Antarctic
      organisms have received little attention. Possibly the most important of these is
      the timing and availability of resources, and the way in which this dictates the
      tempo or pace of life. The clearest view of this effect comes from comparisons of
      species living in different habitats. Here, we (i) show that the timing and
      extent of resource availability, from nutrients to colonisable space, differ
      across Antarctic marine, intertidal and terrestrial habitats, and (ii) illustrate
      that these differences affect the rate at which organisms function. Consequently,
      there are many dramatic biological differences between organisms that live as
      little as 10 m apart, but have gaping voids between them ecologically.
      Identifying the effects of environmental timing and predictability requires
      detailed analysis in a wide context, where Antarctic terrestrial and marine
      ecosystems are at one extreme of the continuum of available environments for many
      characteristics including temperature, ice cover and seasonality.
      Anthropocentrically, Antarctica is harsh and as might be expected terrestrial
      animal and plant diversity and biomass are restricted. By contrast, Antarctic
      marine biotas are rich and diverse, and several phyla are represented at levels
      greater than global averages. There has been much debate on the relative
      importance of various physical factors that structure the characteristics of
      Antarctic biotas. This is especially so for temperature and seasonality, and
      their effects on physiology, life history and biodiversity. More recently,
      habitat age and persistence through previous ice maxima have been identified as
      key factors dictating biodiversity and endemism. Modern molecular methods have
      also recently been incorporated into many traditional areas of polar biology.
      Environmental predictability dictates many of the biological characters seen in
      all of these areas of Antarctic research.

PMID- 16293197
TI  - Independent component analysis as a rotation method: a very different solution to
      Thurstone's box problem.
AB  - In this paper we consider the well-known Thurstone box problem in exploratory
      factor analysis. Initial loadings and components are extracted using principal
      component analysis. Rotating the components towards independence rather than
      rotating the loadings towards simplicity allows one to accurately recover the
      dimensions of each box and also produce simple loadings. It is shown how this may
      be done using an appropriate rotation criterion and a general rotation algorithm.
      Methods from independent component analysis are used, and this paper may be
      viewed as an introduction to independent component analysis from the perspective
      of factor analysis.

PMID- 16293194
TI  - Review of the twelfth West Coast Retrovirus Meeting.
AB  - Every year the Cancer Research Institute from University of California at Irvine
      organizes the West Coast Retrovirus Meeting where participants have a chance to
      discuss the latest progress in understanding the pathology of retroviruses. The
      12th meeting was held at the Hyatt Regency Suites in Palm Springs, California
      from October 6th to October 9th 2005, with the major focus on human
      immunodeficiency virus (HIV) pathogenesis. Philippe Gallay from The Scripps
      Research Institute and Thomas J. Hope from Northwestern University organized the
      meeting, which covered all the steps involved in the lifecycle of retroviruses
      with an emphasis on virus:host interactions. The trend in research appeared to be
      on the restriction of viral infection, both by the endogenous, cellular
      restriction factors, as well as by the potential antimicrobial compounds of known
      or unknown mechanisms. Additionally, new stories on the inevitable feedback from
      the host immune system were presented as well. HIV still represents a challenge
      that an army of motivated people has been working on for over 20 years. And yet,
      the field has not reached the plateau in knowledge nor enthusiasm, which was
      proven again in October 2005 in Palm Springs.

PMID- 16293198
TI  - Four improved statistics for contrasting means by correcting skewness and
      kurtosis.
AB  - This paper is concerned with removing the influence of non-normality in the
      classical t-statistic for contrasting means. Using higher-order expansion to
      quantify the effect of non-normality, four corrected statistics are provided. Two
      aim to correct the mean bias and two to correct the overall distribution. The
      classical t-statistic is also robust against non-normality when the observed
      variables satisfy certain structures. A special case is when the marginal
      distributions of the contrast are independent and identically distributed.

PMID- 16293199
TI  - Computerized adaptive testing: a mixture item selection approach for constrained
      situations.
AB  - In computerized adaptive testing (CAT), traditionally the most discriminating
      items are selected to provide the maximum information so as to attain the highest
      efficiency in trait (theta) estimation. The maximum information (MI) approach
      typically results in unbalanced item exposure and hence high item-overlap rates
      across examinees. Recently, Yi and Chang (2003) proposed the multiple
      stratification (MS) method to remedy the shortcomings of MI. In MS, items are
      first sorted according to content, then difficulty and finally discrimination
      parameters. As discriminating items are used strategically, MS offers a better
      utilization of the entire item pool. However, for testing with imposed non
      statistical constraints, this new stratification approach may not maintain its
      high efficiency. Through a series of simulation studies, this research explored
      the possible benefits of a mixture item selection approach (MS-MI), integrating
      the MS and MI approaches, in testing with non-statistical constraints. In all
      simulation conditions, MS consistently outperformed the other two competing
      approaches in item pool utilization, while the MS-MI and the MI approaches
      yielded higher measurement efficiency and offered better conformity to the
      constraints. Furthermore, the MS-MI approach was shown to perform better than MI
      on all evaluation criteria when control of item exposure was imposed.

PMID- 16293200
TI  - On measuring the minimum detection time: a simple reaction time study in the time
      estimation paradigm.
AB  - Kornblum's time estimation paradigm, together with the so-called 'race model',
      provides an appealing alternative for measuring the 'cut-off' which separates
      'true' reaction times from anticipatory reaction times. However, the model is not
      precise enough to reveal the relation between the signal intensity and the 'cut
      off'. Accordingly, Kornblum's model is extended with an emphasis on the measure
      of the 'cut-off'. Another aspect of the extension is to use a parametric method
      to analyse the data. In particular, it is assumed that the time estimation
      induced latency is gamma distributed and the signal-induced latency is Weibull
      distributed, with the latter shifted by the 'cut-off'. The rationale behind the
      parametric assumption is discussed. For illustrative purposes, two pieces of
      experimental work are presented. Since the core of the race model is the
      assumption of an independent race between the time estimation process and the
      detection process, the first experiment tests whether, for the same signal
      intensity, the signal-induced latency distribution is invariant across different
      time intervals; the second experiment tests whether, for the same time interval,
      the time estimation-induced latency distribution is invariant across different
      signal intensity conditions. The data from the second experiment are also used to
      test various parametric assumptions in the model, which include the signal effect
      on the 'cut-off'. The new model fits the data well.

PMID- 16293202
TI  - Studying group and time invariance in maximal reliability for multiple-component
      measuring instruments via covariance structure modelling.
AB  - A method for examining invariance in maximal reliability for weighted
      combinations of congeneric measures is described. The approach is developed
      within the framework of covariance structure modelling and allows one to
      ascertain whether a multi-component instrument consisting of homogeneous measures
      is associated with the same minimal relative error variance in distinct
      populations or over time. The procedure yields as a by-product an interval
      measure of discrepancy in maximal reliability across independent groups or
      assessment occasions, and is illustrated with two examples.

PMID- 16293201
TI  - Estimation of reliability for multiple-component measuring instruments in test
      retest designs.
AB  - A covariance structure modelling method for the estimation of reliability for
      composites of congeneric measures in test-retest designs is outlined. The
      approach also allows an approximate standard error and confidence interval for
      scale reliability in such settings to be obtained. The procedure further permits
      measurement error components due to possible transient condition influences to be
      accounted for and evaluated, and is illustrated with a pair of examples.

PMID- 16293203
TI  - Bicriterion methods for partitioning dissimilarity matrices.
AB  - Partitioning indices associated with the within-cluster sums of pairwise
      dissimilarities often exhibit a systematic bias towards clusters of a particular
      size, whereas minimization of the partition diameter (i.e. the maximum
      dissimilarity element across all pairs of objects within the same cluster) does
      not typically have this problem. However, when the partition-diameter criterion
      is used, there is often a myriad of alternative optimal solutions that can vary
      significantly with respect to their substantive interpretation. We propose a
      bicriterion partitioning approach that considers both diameter and within-cluster
      sums in the optimization problem and facilitates selection from among the
      alternative optima. We developed several MATLAB-based exchange algorithms that
      rapidly provide excellent solutions to bicriterion partitioning problems. These
      algorithms were evaluated using synthetic data sets, as well as an empirical
      dissimilarity matrix.

PMID- 16293204
TI  - Bicriterion seriation methods for skew-symmetric matrices.
AB  - The decomposition of an asymmetric proximity matrix into its symmetric and skew
      symmetric components is a well-known principle in combinatorial data analysis.
      The seriation of the skew-symmetric component can emphasize information
      corresponding to the sign or absolute magnitude of the matrix elements, and the
      choice of objective criterion can have a profound impact on the ordering. In this
      research note, we propose a bicriterion approach for seriation of a skew
      symmetric matrix incorporating both sign and magnitude information. Two numerical
      demonstrations reveal that the bicriterion procedure is an effective alternative
      to direct seriation of the skew-symmetric matrix, facilitating favourable trade
      offs among sign and magnitude information.

PMID- 16293205
TI  - Influence curves for factor loadings.
AB  - Influence curves for the initial and rotated loadings are derived for the maximum
      likelihood factor analysis (MLFA) model. Cook's distances based on the empirical
      influence curves of factor loadings are proposed for the identification of
      influential observations. The distances are shown to be invariant under scale
      transformation and factor rotation. We find that an observation with a very large
      Cook's distance based on the sample influence curve may not necessarily exert an
      excessive influence on the factor loadings pattern but may change the ordering of
      the factors. The issue of the switching of factors is also studied by means of
      the empirical influence curve and factor scores.

PMID- 16293206
TI  - Latent variable models for misclassified polytomous outcome variables.

PMID- 16293208
TI  - The roles of orphan nuclear receptors in the development and function of the
      immune system.
AB  - Hormones and their receptors regulate cell growth, differentiation and apoptosis
      and also play important roles in immune function. Recent studies on the subfamily
      of the orphan nuclear receptors known as retinoid-acid related orphan receptors
      (ROR) have shed important insights on the roles of this group of nuclear proteins
      in the development and function of the immune system. RORalpha regulates
      inflammatory cytokine production in both innate and adaptive immune system while
      RORgamma regulates the normal development of T lymphocyte repertoire and
      secondary lymphoid organs.

PMID- 16293209
TI  - Mast cell and immune inhibitory receptors.
AB  - Modulation by balancing activating and inhibitory receptors constitutes an
      important mechanism for regulating immune responses. Cells that are activated
      following ligation of receptors bearing immunoreceptor tyrosine-based activation
      motifs (ITAMs) can be negatively regulated by other receptors bearing immuno
      receptor tyrosine-based inhibition motifs (ITIMs). Human mast cells (MCs) are the
      major effector cells of type I hypersensitivity and important participants in a
      number of disease processes. Antigen-mediated aggregation of IgE bound to its
      high-affinity receptor on MCs initiates a complex series of biochemical events
      leading to MC activation. With great detailed description and analysis of several
      inhibitory receptors on human MCs, a central paradigm of negative regulation of
      human MC activation by these receptors has emerged.

PMID- 16293210
TI  - Transcriptional crosstalk between nuclear receptors and cytokine signal
      transduction pathways in immunity.
AB  - The nuclear receptor superfamily and the transcriptional factors associated with
      cytokines are inherently different families of signaling molecules and activate
      gene transcription by binding to their respective responsive element. However, it
      has become increasingly clear from our works and others that nuclear receptors
      are important regulators of cytokine production and function through complex and
      varied interactions between these distinct transcriptional factors. This review
      provides a general overview of the mechanism of action of nuclear receptors and
      their transcriptional crosstalk with transcriptional factors associated with
      cytokine transduction pathways. One of the most important mechanistic aspects is
      protein to protein interaction through a direct or co-regulator-mediated indirect
      manner. Such crosstalk is crucially involved in physiological and therapeutic
      roles of nuclear receptors and their ligands in immunity, inflammation and
      cytokine-related tumors.

PMID- 16293211
TI  - Advances in NF-kappaB signaling transduction and transcription.
AB  - The molecular mechanisms for NF-kappaB signaling transduction and transcription
      have been the most attractive subjects for both basic research and pharmaceutical
      industries due to its important roles in both physiological and pathogenesis,
      particularly the close association of dysregulated NF-kappaB with tumorgenesis
      and inflammation. Several novel intracellular molecular events that regulate NF
      kappaB activity have been described recently, including the discovery of an
      alternative signaling pathway that appears inducing a specific subset genes
      involved in adoptive immune response. Multi-level and multi-dimensional
      regulation of NF-kappaB activity by phosphorylation and acetylation modifications
      have unveiled and became the hottest targets for potentially tissue specific
      molecular interventions. Another emerging mechanism for NF-kappaB-responsive
      gene's regulation where NF-kappaB participates the transcriptional regulation
      independent of its cognate regulatory binding site within the target gene's
      promoter but facilitating the transaction activity of other involved
      transcription factors, that implicated an novel transcriptional activities for NF
      kappaB. Thus, the current review will focus on these recent progresses that have
      been made on NF-kappaB signaling transduction and transcription.

PMID- 16293212
TI  - Current understanding and therapy of asthma workshop summary.
AB  - The prevalence of asthma has increased globally in the past 2 decades. To address
      this critical issue, a workshop on "Current Understanding and Therapy of Asthma"
      was recently held in Beijing, as a part of the 10th International Conference of
      the Society of Chinese Bioscientists in America (SCBA). Several pertinent topics
      were addressed by leading experts from China, Taiwan, Japan and the US, which
      include epidemiology, the molecular genetic mechanism, pathogenesis, treatment
      and prevention of asthma. This article highlights the issues presented and
      discussed in this ground-breaking symposium emphasizing this important public
      health problem in the Chinese population.

PMID- 16293213
TI  - Altered allogeneic immune responses in middle-aged mice.
AB  - It is well known that leukocyte composition, T cell phenotypes and immune
      function change in aged mice and humans. However, limited and conflicting results
      on the age-related immune changes in middle-aged mice were reported.
      Identification of the characteristics of allogeneic immune responses in aging
      mice may offer important information for transplantation immunology. The major
      age-related changes in the immune cell phenotypes and function of 12 months old
      mice include: 1) the significantly decreased CD4+ cell population in the
      peripheral blood, the major peripheral CD4+ cells is CD45RB(low)CD62L(low) memory
      phenotype; 2) the in vitro responses to alloantigens and Con A of splenocytes
      markedly reduced; 3) the in vivo secondary humoral immune responses to
      alloantigens significantly declined; 4) the age-related alteration in the thymus
      mainly occurred in CD4/CD8 double positive (DP) stage; and 5) increased CD80+ and
      MHC class II+ cell population in spleens. Thus, the major age-related immune
      changes in 12 months old mice occurred in CD4+ T cells in the periphery and DP
      stage in the thymus, which may subsequently lead to the decreased allogeneic
      immune responses and the different sensitivity to immunosuppressive drugs and
      treatments. Further studies on the characteristics of allogeneic immunity in
      aging individuals may help to determine the appropriated treatment for transplant
      aging individuals.

PMID- 16293214
TI  - Novel function of TNF cytokines in regulating bone marrow B cell survival.
AB  - Two newly identified tumor necrosis factor (TNF) family cytokines, B cell
      activation factor from the TNF family (BAFF) and a proliferation-inducing ligand
      (APRIL), have recently been shown to enhance the maturation and survival of
      peripheral B cells. However, whether BAFF and APRIL are expressed in the bone
      marrow (BM) microenvironment and if these two cytokines modulate early B cell
      development remain unclear. In the present study, we have detected the abundant
      expression of BAFF and APRIL transcripts in BM non-lymphoid cells. Low levels of
      BAFF and APRIL mRNA are also found in developing B cells. Furthermore, we have
      determined the expression patterns of BAFF receptors during B lymphopoiesis. In
      cultures, both recombinant BAFF and APRIL significantly promote the survival of
      precursor B cells whereas only BAFF can suppress apoptosis of immature B cells.
      These findings suggest that BAFF and APRIL, in addition to their well established
      role in regulating peripheral B cell growth, can modulate the survival of
      developing B cells in the BM.

PMID- 16293215
TI  - Specific antitumor effects of tumor vaccine produced by electrofusion between
      osteosarcoma cell and dendritic cell in rats.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells capable of inducing
      primary T-cell responses. Several immunotherapy treatment strategies involve
      manipulation of DCs, both in vivo and ex vivo, to promote the immunogenic
      presentation of tumor-associated antigens. In this study, an electrofusion
      protocol was developed to induce fusion between osteosarcoma cells and allogeneic
      bone marrow-derived DCs. Preimmunization with irradiated electrofusion products
      was found to provide partial or complete protection from tumor challenge in the
      UMR106 tumor model. Vaccinated survivors developed long immunological memory. The
      therapeutic potential of this type of approach was suggested by the ability of
      UMR106-DC electrofusion products which could induce tumor rejection in a
      substantial percentage (60%) of hosts bearing pre-established tumor cells. These
      results tended to indicate that treatment with electrofused tumor cells and
      allogeneic DCs might be capable of inducing a potent antitumor response and could
      conceivably be applied to a wide range of cancer indications for which tumor
      associated antigens have not been identified.

PMID- 16293216
TI  - Preliminary study on mouse interleukin-21 application in tumor gene therapy.
AB  - Interleukin-21 (IL-21) is a recently characterized T cell-derived cytokine with a
      significant homology to IL-2, IL-4 and IL-15. To determine whether IL-21 has
      broad immunoregulatory activity and can stimulate durable antitumour responses,
      we constructed mouse IL-21 (mIL-21) recombinant plasmid and evaluated its
      antitumor efficacy. Mouse IL-21 cDNA was amplified from Con A-activated mouse T
      cells by RT-PCR. Recombinant pcDNA3.1/mIL-21 was constructed and transfected into
      Sp2/0 cells. Mouse IL-21 expression was analyzed by Western blotting and its
      activities were detected by 3H-TdR incorporation and MTT assay. The recombinant
      pcDNA3.1/mIL-21 was injected s.c. into tumor lump. Tumor size, weight, the
      activities of CTLs, NK cells and LAK cells and serum IFN-gamma level were
      measured for evaluating mIL-21 mediated antitumor responses. The results
      indicated that mIL-21 was correctly expressed in Sp2/0 cells and it can improve
      the proliferation of T cells and B cells, and enhance NK cytotoxic activity in
      vitro. The activities of CTL and NK cells, and serum IFN-gamma level were
      significantly improved, furthermore the tumor growth was obviously suppressed in
      pcDNA3.1/mIL-21 treated mice. However, the LAK activity did not alter
      significantly. Taken together, this study suggests that the injection with
      recombinant plasmid containing mIL-21 is a potential approach for tumor gene
      therapy.

PMID- 16293217
TI  - The role of innate immune cells in the response of heat-treated Mycobacterium
      tuberculosis (M.tb) antigens stimulating PBMCs.
AB  - The proliferation response of gammadelta T cells to the antigen from heat-treated
      Mycobacterium tuberculosis H37Ra (M.tb Ag) was used as a good model in
      gammadeltaT cell research. From preliminary research it is found that activated
      NK cells positively elevated gammadeltaT cells proliferation after simulating
      PBMCs with M.tb Ag. To investigate different behaviors of NK cells, gammadeltaNKT
      cells, gammadeltaT cells and relationships between these cell subsets, activation
      and proliferation of different cell subsets of PBMCs in response to M.tb Ag were
      analyzed. We demonstrated that NK cells, gammadeltaNKT cells and gammadeltaT
      cells could be activated after stimulation with M.tb Ag. gammadeltaNKT cells and
      gammadelta T cells proliferated while the number of NK cells decreased after 11
      day-simulation with M.tb Ag. Meanwhile, at the early time of stimulation the
      cytotoxicity of PBMCs was enhanced.

PMID- 16293218
TI  - Activation of signal transducer and activator of transcription 5 (STAT5) in
      splenocyte proliferation of asthma mice induced by ovalbumin.
AB  - To investigate the role of signal transducer and transcriptional activator 5
      (STAT5) activated in ovalbumin (OVA)-induced splenocyte proliferation of asthma
      mice, an asthma mouse model was set up by intraperitoneal injection and
      aspiration of OVA with nebulizer. The proliferation of splenocytes isolated from
      the asthma mice was detected by [3H] thymidine incorporation. The phosphorylation
      of STAT5 was examined by Western blotting and STAT5-DNA binding was measured by
      electrophoretic mobility shift assay (EMSA). OVA could pronouncedly induce the
      splenocyte proliferation of asthma mice in a dose-dependent manner compared with
      control groups. Phosphorylation of STAT5 and STAT5-DNA binding were observed in
      splenocytes from asthma mice induced by OVA at 1 h and 3 h. These results
      indicated that STAT5 signal pathway played an important role in lymphocyte
      proliferation of asthma mice induced by OVA.

PMID- 16293219
TI  - Is rigorous punishment effective? A case study of lifetime license revocation in
      Taiwan.
AB  - This study investigated the effectiveness of administrative lifetime driver's
      license revocation (ALLR) and its impact on offenders, based on a two-stage
      survey of 768 offenders. It was found that after ALLR had been imposed, 23.4% of
      these offenders were still driving almost the same as before, 59.8% drove
      significantly less frequently, and only 16.8% of the offenders gave up driving
      completely. The results of logistic regression models showed that offenders'
      compliance with ALLR was significantly correlated with their personal
      characteristics (age, income), penalty status (incarceration, duration of ALLR),
      and the need to drive for working, commuting and shopping. Elderly and low-income
      offenders were more likely to abide by the ALLR restriction. The application of
      the generalized estimating equations (GEE) model was used to identify the
      determinant factors affecting offenders' driving mileage, and to effectively
      estimate the driving mileage reduction as a result of the ALLR. It was found that
      ALLR is fairly effective in keeping offenders off the road, but that it may
      reduce their ability to make a living, resulting in the less fortunate becoming
      more helpless.

PMID- 16293220
TI  - [Hepatoid adenocarcinoma of the stomach. A case report].
AB  - Hepatoid adenocarcinoma of the stomach is a very rare tumor with a poor
      prognosis. Lymph nodes involvement and/or liver metastases are frequently
      observed. Diagnosis should be pointed out if elevated serum level of alpha
      fetoprotein (AFP) is detected with gastric tumor. Histologically, the tumor is an
      adenocarcinoma of intestinal type including foci of hepatoid differenciation.
      Immunohistochemistry is positive for alpha-1-antitrypsin and alpha-1
      antichymotripsin, and for AFP. We report a case of a 66 year-old man presenting
      an advanced stage of hepatoid adenocarcinoma of the stomach, treated by
      gastrectomy followed by chemotherapy. The patient died four months after the
      surgery because of progressing liver metastatic disease.

PMID- 16293221
TI  - Renal cytoplasmic proteasome proteinase activities are altered in chronic renal
      failure.
AB  - The effect of uremia on renal cortex cytoplasmic proteasomes was examined by
      comparing proteasomes isolated from 5/6th nephrectomy rats 3-months post-surgery
      and age-matched control rats with normal renal function. ATP-dependent proteasome
      activity was reduced 50% in chronic renal failure rats (CRF) 3-months post
      surgery compared to age-matched control rats. Trypsin-like (T-like) proteasome
      activity was decreased 90% compared to 70% for caspase-like activity (PGPHase)
      and 30% for chymotrypsin-like activity (C-like). ATP-independent proteasome
      activity was decreased 60% in CRF rats 3-months post-surgery. ATP-independent
      renal cortex proteasome T-like activity in CRF rats was 4% of age-matched control
      rats. C-like and PGPHase activities were 60% and 50% of age-matched controls,
      respectively. Uremia was associated with decreased 26S proteasome beta subunits.
      CRF rat 26S proteasomes had decreased levels of beta1, beta3, alpha4, and alpha7
      abundances. Compared to age-matched control rats with normal renal function, CRF
      rats had a 25% increase in ubiquitinated cytoplasmic proteins. Decreased renal
      cytoplasmic proteasome activity may play a role in renal tubule hypertrophy
      common to renal diseases associated with decreased functioning nephrons.

PMID- 16293222
TI  - The mitochondrial channel VDAC has a cation-selective open state.
AB  - The mitochondrial channel VDAC is known to have two major classes of functional
      states, a large conductance "open" state that is anion selective, and lower
      conductance substates that are cation selective. The channel can reversibly
      switch between open and half-open states, with the latter predominant at
      increasing membrane voltages of either polarity. We report the presence of a new
      functional state of VDAC, a cation-selective state with conductance approximately
      equal to that of the canonical open state. This newly described state of VDAC can
      be reached from either the half-open cation-selective state or from the open
      anion-selective state. The latter transition implies that a mechanism exists for
      selectivity gating in VDAC that is separate from partial closure, which may be
      relevant to the physiological regulation of this channel and mitochondrial outer
      membrane permeability.

PMID- 16293224
TI  - Interactions between collagen IX and biglycan measured by atomic force
      microscopy.
AB  - The stability of the lattice-like type II collagen architecture of articular
      cartilage is paramount to its optimal function. Such stability not only depends
      on the rigidity of collagen fibrils themselves, but more importantly, on their
      interconnections. One known interconnection is through type IX and biglycan
      molecules. However, the mechanical properties of this interaction and its role in
      the overall stability remain unrevealed. Using atomic force microscopy, this
      study directly measured the mechanical strength (or the rupture force) of a
      single bond between collagen IX and biglycan. The results demonstrated that the
      rupture force of this single bond was 15pN, which was significantly smaller than
      those of other known molecule interactions to date. This result suggested that
      type IX collagen and biglycan interaction may be the weak link in the cartilage
      collagen architecture, vulnerable to abnormal joint force and associated with
      disorders such as osteoarthritis.

PMID- 16293223
TI  - Proteolipid of vacuolar H(+)-ATPase of Plasmodium falciparum: cDNA cloning, gene
      organization and complementation of a yeast null mutant.
AB  - Vacuolar H(+)-ATPase (V-ATPase), an electrogenic proton pump, is highly expressed
      in Plasmodium falciparum, the human malaria parasite. Although V-ATPase-driven
      proton transport is involved in various physiological processes in the parasite,
      the overall features of the V-ATPase of P. falciparum, including the gene
      organization and biogenesis, are far less known. Here, we report cDNA cloning of
      proteolipid subunit c of P. falciparum, the smallest and most highly hydrophobic
      subunit of V-ATPase. RT-PCR analysis as well as Northern blotting indicated
      expression of the proteolipid gene in the parasite cells. cDNA, which encodes a
      complete reading frame comprising 165 amino acids, was obtained, and its deduced
      amino acid sequence exhibits 52 and 57% similarity to the yeast and human
      counterparts, respectively. Southern blot analysis suggested the presence of a
      single copy of the proteolipid gene, with 5 exons and 4 introns. Upon
      transfection of the cDNA into a yeast null mutant, the cells became able to grow
      at neutral pH, accompanied by vesicular accumulation of quinacrine. In contrast,
      a mutated proteolipid with replacement of glutamate residue 138 with glutamine
      did not lead to recovery of the growth ability or vesicular accumulation of
      quinacrine. These results indicated that the cDNA actually encodes the
      proteolipid of P. falciparum and that the proteolipid is functional in yeast.

PMID- 16293225
TI  - Generation and characterization of Sca2 (ataxin-2) knockout mice.
AB  - Ataxin-2, the gene product of the Spinocerebellar Ataxia Type 2 (SCA2) gene, is a
      protein of unknown function with abundant expression in embryonic and adult
      tissues. Its interaction with A2BP1/Fox-1, a protein with an RNA recognition
      motif, suggests involvement of ataxin-2 in mRNA translation or transport. To
      study the effects of in vivo ataxin-2 function, we generated an ataxin-2
      deficient mouse strain. Ataxin-2 deficient mice were viable. Genotypic analysis
      of litters from mating of heterozygous mice showed segregation distortion with a
      significant reduction in the birth of Sca-/- females. Detailed macroscopic and
      microscopic analysis of surviving nullizygous Sca2 knockout mice showed no major
      histological abnormalities. On a fat-enriched diet, ataxin-2 deficient animals
      had increased weight gain. Our results demonstrate that ataxin-2, although widely
      expressed, is not essential in development or during adult survival in the mouse,
      but leads to adult-onset obesity.

PMID- 16293226
TI  - Inhibition of platelet aggregation by anthrax edema toxin.
AB  - Edema toxin is a key virulence determinant in anthrax pathogenesis that causes
      augmentation of cAMP inside host cells. This exotoxin has been implicated in
      facilitating bacterial invasion by impairing host defenses. Here, we report for
      the first time that edema toxin plays an important role in suppression of
      platelet aggregation; an effect that could be of vital significance in anthrax
      afflicted subjects. It was found that edema toxin induces a dose dependent and
      time dependent increase in cAMP inside rabbit platelets. Elevation of cAMP led to
      suppression of platelet aggregation as demonstrated by in vitro aggregation
      assays. A 95% suppression of platelet aggregation in response to thrombin and a
      complete suppression in response to ADP, at toxin concentrations of 7 and 2.2 nM,
      respectively, were observed. Antibody neutralized wild type edema factor and non
      toxic mutants of this binary toxin failed to show any alteration in the normal
      aggregation pattern. Edema toxin caused the activation of cAMP dependent protein
      kinase A inside platelets, a phenomenon that could be speculated to initiate the
      cascade of events responsible for suppressing platelet aggregation. Furthermore,
      in vivo bleeding time registered a sharp increase in response to edema toxin.
      These findings can explicate the systemic occurrence of hemorrhage, which is a
      prominent symptom of anthrax. This study exemplifies how Bacillus anthracis has
      evolved the ability to use host's physiological processes by mimicking the
      eukaryotic signal transduction machinery, thus inflicting persistent infection.

PMID- 16293227
TI  - CHF1/Hey2 suppresses SM-MHC promoter activity through an interaction with GATA-6.
AB  - The bHLH transcription factor CHF1/Hey2 has been previously shown to regulate
      neointimal formation after vascular injury, but the mechanisms have not been
      fully elucidated. The zinc-finger protein GATA-6 has also been shown to regulate
      vascular smooth-muscle phenotype through regulation of smooth-muscle contractile
      protein gene expression. To address the potential mechanisms by which CHF1/Hey2
      regulates vascular smooth-muscle phenotype switching, we investigated the effect
      of CHF1/Hey2 on GATA-6-dependent smooth-muscle myosin heavy chain promoter
      activity. When cotransfected into NIH3T3 cells, CHF1/Hey2 reduced GATA-6
      dependent activation of the promoter by 90%. Exogenous p300 was not sufficient to
      overcome this repression effect, demonstrating that the inhibitor effect did not
      involve coactivation by p300. Coimmunoprecipitation studies demonstrated that
      CHF1/Hey2 interacts directly with GATA-6. Mutational analysis demonstrated that
      the bHLH domain is required for transcriptional repression. Our findings
      highlight an important transcriptional mechanism by which CHF1/Hey2 may affect
      smooth-muscle cell phenotype.

PMID- 16293228
TI  - Peroxynitrite-induced mitochondrial translocation of PKCalpha causes U937 cell
      survival.
AB  - Our previous work has shown that non-toxic concentrations of peroxynitrite
      nevertheless commit U937 cells to mitochondrial permeability-transition (MPT)
      dependent necrosis that is however prevented by a parallel survival signaling
      pathway involving cytosolic phospholipase A2 (cPLA2)-dependent arachidonic acid
      release and PKCalpha activation associated with the cytosolic translocation of
      Bad. The present study provides evidence of an early mitochondrial translocation
      of PKCalpha. Inhibition of the survival signaling at the level of either cPLA2,
      or PKC, was invariably associated with prevention of the mitochondrial
      localization of PKCalpha, with the mitochondrial translocation of Bad and Bax and
      with a very rapid lethal response. Collectively, the results presented in this
      study demonstrate that peroxynitrite, while committing U937 cells to necrosis,
      triggers a parallel signaling response leading to the cytosolic localization of
      two important members of the Bcl-2 family implicated in the onset of MPT.

PMID- 16293229
TI  - Inositol polyphosphate multikinase regulates inositol 1,4,5,6-tetrakisphosphate.
AB  - The human inositol phosphate multikinase (IPMK, 5-kinase) has a preferred 5
      kinase activity over 3-kinase and 6-kinase activities and a substrate preference
      for inositol 1,3,4,6-tetrakisphosphate (Ins(1,3,4,6)P4) over inositol 1,4,5
      trisphosphate (Ins(1,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate
      (Ins(1,3,4,5)P4). We now report that the recombinant human protein can catalyze
      the conversion of inositol 1,4,5,6-tetrakisphosphate (Ins(1,4,5,6)P4) to
      Ins(1,3,4,5,6)P5 in vitro; the reaction product was identified by HPLC to be
      Ins(1,3,4,5,6)P5. The apparent Vmax was 42 nmol of Ins(1,3,4,5,6)P5 formed/min/mg
      protein, and the apparent Km was 222 nM using Ins(1,3,4,6)P4 as a substrate; the
      catalytic efficiency was similar to that for Ins(1,4,5)P3. Stable over-expression
      of the human protein in HEK-293 cells abrogates the in vivo elevation of
      Ins(1,4,5,6)P4 from the Salmonella dublin SopB protein. Hence, the human 5-kinase
      may also regulate the level of Ins(1,4,5,6)P4 and have an effect on chloride
      channel regulation.

PMID- 16293230
TI  - Hepatocyte-specific deletion of the keap1 gene activates Nrf2 and confers potent
      resistance against acute drug toxicity.
AB  - Nrf2 is a key regulator of many detoxifying enzyme genes, and cytoplasmic protein
      Keap1 represses the Nrf2 activity under quiescent conditions. Germ line deletion
      of the keap1 gene results in constitutive activation of Nrf2, but the pups
      unexpectedly died before weaning. To investigate how constitutive activation of
      Nrf2 influences the detoxification system in adult mice, we generated mice
      bearing a hepatocyte-specific disruption of the keap1 gene. Homozygous mice were
      viable and their livers displayed no apparent abnormalities, but nuclear
      accumulation of Nrf2 is elevated. Microarray analysis revealed that, while many
      detoxifying enzyme genes are highly expressed, some of the typical Nrf2-dependent
      genes are only marginally increased in the Keap1-deficient liver. The mutant mice
      were significantly more resistant to toxic doses of acetaminophen than control
      animals. These results demonstrate that chronic activation of Nrf2 confers
      animals with resistance to xenobiotics without affecting the morphological and
      physiological integrity of hepatocytes.

PMID- 16293231
TI  - Crystal structure of C-terminal desundecapeptide nitrite reductase from
      Achromobacter cycloclastes.
AB  - Monoclinic crystal structure of C-terminal desundecapeptide nitrite reductase
      (NiRc-11) from Achromobacter cycloclastes was determined at 2.6A. NiRc-11 exists
      as a loose trimer in the crystal. Deletion of 11 residues eliminates all
      intersubunit hydrogen bonds mediated by the C-terminal tail. The rigid irregular
      coil 105-112, which constitutes part of the sidewall of the active site pocket,
      undergoes conformational changes and becomes highly flexible in NiRc-11.
      Correspondingly, the linker segments between the two copper sites 95-100 and 135
      136 are partly relaxed in conformation, which leads to disrupted active site
      microenvironments responsible for the activity loss and spectral change of NiRc
      11. Comparison with the native structure revealed a bulky residue Met331 fastened
      by hydrogen bonding, which may play a direct role in keeping the right copper
      site geometry by protruding its side chain against the irregular coil 105-112.
      Sequence alignment showed that the bulky residue is conserved at position 331,
      indicating an equal importance of C-terminal segment in other copper-containing
      nitrite reductases.

PMID- 16293232
TI  - Amitriptyline prevents thermal hyperalgesia and modifications in rat spinal cord
      GABA(B) receptor expression and function in an animal model of neuropathic pain.
AB  - Using an animal model of neuropathic pain, behavioral and biochemical experiments
      were performed to assess the effects of this condition on pain threshold and
      GABA(B) receptor sensitivity and subunit gene expression in the rat lumbar spinal
      cord. The results indicate that partial sciatic nerve ligation decreases thermal
      and mechanical pain withdrawal latencies, and increases baclofen-stimulated
      [35S]GTPgammaS binding and GABA(B) receptor subunit gene expression in the rat
      lumbar spinal cord, suggesting that neuropathic pain may be due, in part, to a
      deficiency in GABAergic transmission. The experiments also demonstrate that daily
      administration (10 mg/kg, i.p.) of amitriptyline, a tricyclic antidepressant used
      for the treatment of neuropathic pain, for 1 week after surgery prevents the
      decline in thermal pain threshold, the increase in GABA(B2) gene expression, and
      development of increased GABA(B) receptor function in spinal cord resulting from
      nerve damage. These findings indicate that the efficacy of amitriptyline as a
      treatment for neuropathic pain may be related to an ability to maintain spinal
      cord GABA(B) receptor activity.

PMID- 16293234
TI  - Characterization of the melatoninergic MT3 binding site on the NRH:quinone
      oxidoreductase 2 enzyme.
AB  - Melatonin acts through a series of molecular targets: the G-protein coupled
      receptors, MT1 and MT2, and a third binding site, MT3, recently identified as the
      enzyme NRH:quinone oxydoreductase 2 (QR2). The relationship between the multiple
      physiological functions of melatonin and this enzyme remains unclear. Because of
      the relationship of QR2 with the redox status of cells, these studies could bring
      the first tools for a molecular rationale of the antioxidant effects of
      melatonin. In the present paper, we used a QR2-stably expressing cell line and
      hamster kidneys to compare the 2-[125I]-iodomelatonin and 2-[125I]-iodo-5
      methoxycarbonylamino-N-acetyltryptamine binding data, and to characterize the MT3
      binding site. We designed and tested compounds from two distinct chemicals series
      in a displacement assay of the two MT3 ligands, 2-[125I]-iodomelatonin and 2
      [125I]-iodo-5-methoxycarbonylamino-N-acetyltryptamine from their cloned target.
      We also tested their ability to inhibit QR2 catalytic activity. These compounds
      were separated into two classes: those that bind within the catalytic site (and
      being inhibitors) and those that bind outside it (and therefore not being
      inhibitors). Compounds range from potent ligands (K(i) = 1 nM) to potent
      inhibitors (14 nM), and include one compound [NMDPEF: N-[2-(2-methoxy-6H
      dipyrido[2,3-a:3,2-e]pyrrolizin-11-yl)ethyl]-2-furamide] active on both
      parameters in the low nanomolar range. To dissect the physio-pathological
      pathways in which QR2, MT3 and melatonin meet, one needs more compounds binding
      to MT3 and/or inhibitors of QR2 enzymatic activity. The compounds described in
      the present paper are new tools for such a task.

PMID- 16293233
TI  - Sensitization of breast carcinoma cells to ionizing radiation by small molecule
      inhibitors of DNA-dependent protein kinase and ataxia telangiectsia mutated.
AB  - DNA-PK and ATM are members of the phosphatidylinositol 3'-kinase like kinase
      (PIKK) family of serine/threonine protein kinases and have critical roles in the
      cellular response to DNA double-strand breaks. Genetic loss of either activity
      leads to pronounced sensitivity to ionizing radiation (IR). Hence, these enzymes
      are potential targets to confer enhanced radiosensitivity on tumour cells. We
      show that novel inhibitors of either DNA-PK or ATM sensitize breast carcinoma
      cells to IR. Radiosensitization was accompanied by an apparent DNA repair deficit
      as measured by the persistence of IR-induced foci of phosphorylated histone H2AX
      (gammaH2AX foci). These specific inhibitors also allowed us to probe the
      biochemistry and kinetics of histone H2AX phosphorylation following gamma
      irradiation in breast cancer cells with the aim of validating H2AX as a biomarker
      for DNA-PK or ATM inhibition in vivo. ATM inhibition reduced the initial average
      intensity of gammaH2AX foci while inhibition of DNA-PK had only a small effect on
      the initial phosphorylation of H2AX. However, simultaneous treatment with both
      compounds dramatically reduced gammaH2AX focus intensity, consistent with the
      reported role of ATM and DNA-PK in IR induced phosphorylation of H2AX.

PMID- 16293235
TI  - Toxicokinetics and toxicodynamics of ochratoxin A, an update.
AB  - Ochratoxin A (OTA) is a mycotoxin produced by fungi of two genera: Penicillium
      and Aspergillus. OTA has been shown to be nephrotoxic, hepatotoxic, teratogenic
      and immunotoxic to several species of animals and to cause kidney and liver
      tumours in mice and rats. Because of differences in the physiology of animal
      species, wide variations are seen in the toxicokinetic patterns of absorption,
      distribution and elimination of the toxin. Biotransformation of OTA has not been
      entirely elucidated. At present, data regarding OTA metabolism are controversial.
      Several metabolites have been characterized in vitro and/or in vivo, whereas
      other metabolites remain to be characterized. Several major mechanisms have been
      shown as involved in the toxicity of OTA: inhibition of protein synthesis,
      promotion of membrane peroxidation, disruption of calcium homeostasis, inhibition
      of mitochondrial respiration and DNA damage. The contribution of metabolites in
      OTA genotoxicity and carcinogenicity is still unclear. The genotoxic status of
      OTA is still controversial because contradictory results were obtained in various
      microbial and mammalian tests, notably regarding the formation of DNA adducts.
      More recent studies are focused on the OTA ability to disturb cellular signalling
      and regulation, to modulate physiological signals and thereby to influence cells
      viability and proliferation. The present paper offers an update on these
      different issues. In addition since humans and animals are likely to be
      simultaneously exposed to several mycotoxins, especially through their diet, the
      little information available on the combined effects of OTA and other mycotoxins
      has also been reviewed.

PMID- 16293236
TI  - Bioscavengers for the protection of humans against organophosphate toxicity.
AB  - Current antidotes for organophosphorus compounds (OP) poisoning consist of a
      combination of pretreatment with carbamates (pyridostigmine bromide), to protect
      acetylcholinesterase (AChE) from irreversible inhibition by OP compounds, and
      post-exposure therapy with anti-cholinergic drugs (atropine sulfate) to
      counteract the effects of excess acetylcholine and oximes (e.g., 2-PAM chloride)
      to reactivate OP-inhibited AChE. These antidotes are effective in preventing
      lethality from OP poisoning, but they do not prevent post-exposure
      incapacitation, convulsions, seizures, performance decrements, or in many cases
      permanent brain damage. These symptoms are commonly observed in experimental
      animals and are likely to occur in humans. The problems intrinsic to these
      antidotes stimulated attempts to develop a single protective drug, itself devoid
      of pharmacological effects, which would provide protection against the lethality
      of OP compounds and prevent post-exposure incapacitation. One approach is the use
      of enzymes such as cholinesterases (ChEs), beta-esterases in general, as single
      pretreatment drugs to sequester highly toxic OP anti-ChEs before they reach their
      physiological targets. This approach turns the irreversible nature of the OP: ChE
      interaction from disadvantage to an advantage; instead of focusing on OP as an
      anti-ChE, one can use ChE as an anti-OP. Using this approach, it was shown that
      administration of fetal bovine serum AChE (FBSAChE) or equine serum
      butyrylcholinesterase (EqBChE) or human serum BChE (HuBChE) protected the animals
      from multiple LD50s of a variety of highly toxic OPs without any toxic effects or
      performance decrements. The bioscavengers that have been explored to date for the
      detoxification of OPs fall into three categories: (A) those that can
      catalytically hydrolyze OPs and thus render them non-toxic, such as OP hydrolase
      and OP anhydrase; (B) those that stoichiometrically bind to OPs, that is, 1 mol
      of enzyme neutralizes one or 2 mol of OP inactivating both, such as ChEs and
      related enzymes; and (C) and those generally termed as "pseudo catalytic", e.g.,
      a combination of ChE and an oxime pre-treatment such that the catalytic activity
      of OP-inhibited ChE can rapidly and continuously be restored in the presence of
      an oxime. Since the biochemical mechanism underlying prophylaxis by exogenous
      esterases such as ChEs is established and tested in several animal species,
      including non-human primates, this concept should allow a reliable extrapolation
      of results from animal experiments to human application. Having being extensively
      investigated by several groups, plasma derived HuBChE is judged to be the most
      suitable bioscavenger for its advancement for human use. The program is being
      developed at the present time for conducting a safety clinical trial in human
      volunteers. Several other candidate bioscavengers will follow; e.g., recombinant
      HuBChE expressed in the milk of transgenic goats, pseudo catalytic scavenger(s),
      e.g., a combination of ChE and oxime, and possibly PON 1 as a catalytic scavenger
      in the future.

PMID- 16293237
TI  - Thermotropic phase behaviour of the pseudobinary mixtures of DPPC/C12E5 and
      DMPC/C12E5 determined by differential scanning calorimetry and ultrasonic
      velocimetry.
AB  - The present paper reports on the phase behaviour of the pseudobinary aqueous
      mixtures of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/pentaethylene
      glycol monododecyl ether (C12E5) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine
      monohydrate (DMPC)/C12E5. Both systems exhibit a variety of mesophases, such as
      lamellar gel, liquid crystalline and micellar phases. The phase diagrams show
      peritectic and eutectic behaviours. The existence of a compound complex is
      established. From the phase diagrams, the temperature dependence of the
      solubilisation parameters is obtained. The phase diagrams, especially with
      respect to the solubilisation process were qualitatively explained assuming that
      the packing of the constituents plays a dominating role. Finally, differential
      scanning calorimetry and ultrasonic velocimetry are compared concerning their
      potentials to determine characteristics of phase transitions in pseudobinary
      phospholipid/surfactant mixtures.

PMID- 16293238
TI  - Lack of hepatic metabolism of C-telopeptides of type I collagen.
AB  - BACKGROUND: Bone biochemical markers have been used in dynamic studies of bone
      metabolism, and, for accurate interpretation of measured marker levels, it is
      essential to have information of extra-skeletal metabolism. Therefore, the
      objective of the present study was to investigate if the circulating C
      telopeptides of type I collagen (CTX) was subject to hepatic extraction. METHODS:
      Splanchnic plasma flow, total plasma volume and the plasma concentration of CTX
      was determined in an artery and the liver vein of eight healthy female
      volunteers. For comparison, the concentration of N-terminal propeptide of type I
      collagen, PINP, was measured. RESULTS: No change in plasma level of CTX could be
      detected over the liver. In contrast, PINP decreased from an average of 52.9
      ng/ml in the artery to 42.4 ng/ml in the vein, corresponding to a 19.8%
      reduction. CONCLUSIONS: The C-telopeptides of type I collagen (CTX) are not
      subject to hepatic metabolism.

PMID- 16293239
TI  - Modelling non-stationary variance in EEG time series by state space GARCH model.
AB  - We present a new approach to modelling non-stationarity in EEG time series by a
      generalized state space approach. A given time series can be decomposed into a
      set of noise-driven processes, each corresponding to a different frequency band.
      Non-stationarity is modelled by allowing the variances of the driving noises to
      change with time, depending on the state prediction error within the state space
      model. The method is illustrated by an application to EEG data recorded during
      the onset of anaesthesia.

PMID- 16293240
TI  - An intelligent system for automatic detection of gastrointestinal adenomas in
      video endoscopy.
AB  - Today 95% of all gastrointestinal carcinomas are believed to arise from adenomas.
      The early detection of adenomas could prevent their evolution to cancer. A novel
      system for the support of the detection of adenomas in gastrointestinal video
      endoscopy is presented. Unlike other systems, it accepts standard low-resolution
      video input thus requiring less computational resources and facilitating both
      portability and the potential to be used in telemedicine applications. It
      combines intelligent processing techniques of SVMs and color-texture analysis
      methodologies into a sound pattern recognition framework. Concerning the system's
      accuracy this was measured using ROC analysis and found to exceed 94%.

PMID- 16293241
TI  - Adjacent pioneer commissural interneuron growth cones switch from contact
      avoidance to axon fasciculation after midline crossing.
AB  - Commissural interneurons (CI) of the vertebrate spinal cord are guided ventrally
      toward the floor plate, but subsequently cross the midline and select a
      longitudinal fascicle at specific dorsal-ventral (D-V) positions. We examined at
      high resolution the detailed behaviors of individual pathfinding CI growth cones
      on the ipsilateral and contralateral sides of the spinal cord of living Xenopus
      embryos. We find that pre-crossing CI growth cones exhibit distinct pathfinding
      behaviors compared to post-crossing axons and that the behavioral switch occurs
      immediately upon crossing to the contralateral side. Groups of pioneer
      commissural axons typically extend simultaneously toward the ventral midline
      following discrete paths with separation between adjacent commissurals apparently
      maintained through contact inhibition. In contrast, shortly after crossing the
      midline, commissural axons turn longitudinally and begin to fasciculate with
      other crossed CIs. However, growth cones of crossed commissurals often select
      their final D-V longitudinal track through a series of rapid step-like dorsal
      adjustments that may be due to differential fasciculation with longitudinal
      axons. Together, our results suggest that guidance of commissural axons is
      controlled in part through interactions among CIs that switch rapidly from
      avoidance to fasciculation after midline crossing.

PMID- 16293242
TI  - Characterization of prostaglandin E1 transport by rat renal cortical slices.
AB  - The purpose of this study was to examine prostaglandin E1 (PGE1) transport in rat
      kidney. [3H]PGE1 administered intravenously was accumulated most abundantly in
      the renal cortex. Infusion of probenecid and bromcresol green (BCG) decreased
      [3H]PGE1 accumulation in the renal cortex after injection of [3H]PGE1. To further
      investigate PGE1 transport in the kidney, [3H]PGE1 uptake by renal cortical
      slices was examined. Probenecid and BCG inhibited [3H]PGE1 uptake by the slices.
      Unlabeled PGE1 decreased [3H]PGE1 uptake by renal cortical slices in a
      concentration-dependent manner. The inhibitory effect of various dicarboxylates
      with different carbon atoms on [3H]PGE1 uptake was maximal at 6 carbon atoms.
      Preloading cortical slices with glutarate significantly increased [3H]PGE1
      uptake. [3H]PGE1 uptake was inhibited by various eicosanoids and compounds with
      other structures (p-aminohippurate, benzylpenicillin, estrone-3-sulfate, etc.).
      These findings suggest that PGE1 uptake by renal cortical slices may be mediated
      by the members of the organic anion transporter family.

PMID- 16293243
TI  - Manganese-induced apoptosis in hepatocytes after partial hepatectomy.
AB  - To investigate the apoptosis induced by manganese (Mn) in hepatocytes in vivo,
      rats received a single injection of manganese chloride immediately after partial
      hepatectomy. Characteristic DNA fragmentation was observed at 4 h after partial
      hepatectomy with Mn-injection. The activation of caspase-3 by Mn-injection was
      detected as early as 30 min and peaked at 1 h after partial hepatectomy. The
      activity of Jun N-terminal kinase (JNK) increased to a maximal level, which was
      about 10-fold the maximal level of the control, at 15 min after partial
      hepatectomy and this increase was maintained for 4 h in Mn-injected rats, while a
      transient increase was observed at 1 h in the control. No effect of the Mn
      injection on the activation of p38 mitogen-activated protein kinase (MAPK) was
      observed. Western blot analysis revealed that the injection of Mn markedly
      increased c-Jun and phosphorylated c-Jun protein levels at 1 h after partial
      hepatectomy. An increase in p53 was also observed at 30 min after the Mn
      injection and followed by the upregulation of p21(WAF1/CIP1) protein expression
      at 2 h after partial hepatectomy. These results suggested that the activation of
      JNK and the upregulation of c-Jun, p53 and p21(WAF1/CIP1) were involved in the
      apoptosis of hepatocytes induced by partial hepatectomy with manganese.

PMID- 16293244
TI  - Neuropeptide Y as a partial agonist of the Y1 receptor.
AB  - In absence of receptor cycling, human/rat neuropeptide Y was found to
      persistently occupy the guinea pig neuropeptide Y Y1 receptors expressed on the
      surface of Chinese hamster ovary (CHO) cells (IC50 approximately 8 nM); a lasting
      occupancy was also evident with active receptor cycling. A similar blockade was
      obtained with the human neuropeptide Y Y1 receptor (in CHO or SK-N-MC cells).
      Peptidic antagonists GR238118 (1229U91) and VD-11 blocked the Y1 receptor in the
      same molarity range. A neuropeptide Y-related Y1 agonist, (Leu31Pro34) human
      neuropeptide Y, also strongly adhered to the Y1 site. Similar blockade-like
      occupancy by neuropeptide Y was found with particulates from Y1-expressing CHO
      cells, and with native neuropeptide Y Y1 receptors of rat synaptosomes. Peptide
      YY and a related Y1-selective agonist, (Leu31Pro34) human peptide YY, showed a
      much less stable binding to the neuropeptide Y Y1 receptor with either the intact
      cells or particulates. The Y1 binding of neuropeptide Y was also less sensitive
      to chaotropic agents and guanine nucleotides than the binding of peptide YY,
      indicating a larger stability for association of neuropeptide Y with the
      receptor. Inhibition of forskolin-stimulated adenylyl cyclase showed a distinctly
      attenuating agonism for neuropeptide Y, with an activity similar to peptide YY
      below 1 nM, but considerably lower above 3 nM of the peptides. This activity was
      largely exerted via pertussis toxin-sensitive G-proteins of Y1-CHO cells. Our
      findings indicate that signaling by neuropeptide Y via its Y1 receptor could be
      self-restricting at higher levels of the peptide, in relation to a strong
      association of the agonist with the Y1 binding site.

PMID- 16293245
TI  - Wavelength dependence of intraocular straylight.
AB  - Wavelength dependence of retinal straylight has been a mystery since Stiles in
      1929 [Stiles,W.S., 1929. The scattering theory of the effect of glare on the
      brightness difference threshold. Proc. R. Soc. Lond. (Biol.) 105, 131-41.]
      supposed it to have the strong Rayleigh type lambda(-4) dependence, typical for
      small particle light scattering, but which was never found. Using the accurate
      'compensation comparison' approach, retinal straylight was measured from 625 to
      457 nm. Subjects with a large variety of ocular pigmentation were included.
      Straylight was found to depend strongly on pigmentation of the eye, in addition
      to age. Young and well-pigmented eyes (young negroids) show nearly perfect
      lambda(-4) dependence. With less pigmentation (blue-eyed Caucasians), a red
      dominated component is added, negating the lambda(-4) dependence.

PMID- 16293246
TI  - Inflammatory responses of the substantia nigra after acute hypoxia in neonatal
      rats.
AB  - The neocortex and the striatum are the brain regions most known to be
      particularly vulnerable to acute insults like hypoxia or ischemia. In this work,
      we assess the possibility of cellular damage to the substantia nigra (SN) after
      hypoxia-reoxygenation in the new born rat. The aim of the present paper was to
      evaluate the expression of growth factor IGF-I, and growth factor binding
      proteins IGFBP-3 and IGFBP-5 genes and induction of NOS family members (nNOS,
      eNOS and iNOS) and TNF-alpha genes together with glia activation, in the SN at 5
      and 48 h after severe hypoxia in the 7 day-old rat, a model for the term human
      fetus. At early time, while IGFs remain unchanged, we found a transient increase
      in eNOS and nNOS. Two days after the injury, nNOS expression remained high, iNOS
      and TNF-alpha increased and also GFAP protein expression was observed together
      with a profusion of reactive astrocytes distributed throughout the SN. This study
      on the acute effects of hypoxia on the developing brain provides additional
      insights into the vulnerability of the SN, a brain region involved in
      neurodegenerative pathologies.

PMID- 16293247
TI  - Leishmania donovani: differential activities of classical topoisomerase
      inhibitors and antileishmanials against parasite and host cells at the level of
      DNA topoisomerase I and in cytotoxicity assays.
AB  - Different classes of topoisomerase (TOP) inhibitors and antitrypanosomatid agents
      exhibited variable efficacies against Leishmania donovani parasites and human
      mononuclear cells both at the level of DNA topoisomerase I (TOPI) catalytic
      activity and in cytotoxicity assays. Bis-benzimidazoles and the diamidine
      diminazene aceturate exhibited uniformly high efficacies against parasite and
      host enzymes as well as against parasite and mononuclear cells, but pentamidine
      showed around 2 orders of magnitude greater specificity for Leishmania TOPI and
      amastigote cells (P<0.05). The protoberberine coralyne and the flavonoid
      quercetin were highly potent, but non-selective, inhibitors in vitro, although
      the latter showed slight selectivity for parasite TOPI. Camptothecin was
      selective for mononuclear cells at both levels (P<0.05) and sodium stibogluconate
      was selective only at the enzyme level displaying 30-fold greater potency against
      parasite TOPI (P<0.05). These data suggest that at least part of pentamidines'
      leishmanicidal activity may be mediated through TOPI inhibition, and support the
      feasibility of exploiting differences between Leishmania and human TOPs to
      develop modified compounds with improved selectivity.

PMID- 16293249
TI  - FM1-43 measurements of local exocytotic events in rat melanotrophs.
AB  - We have explored the existence of fusion- and secretion-competent sites on the
      plasma membrane of peptide secreting rat pituitary melanotrophs at rest, and
      following stimulation with glutamate. We monitored changes in fluorescence of FM1
      43, a styryl dye which labels plasma membrane. The results show spontaneous local
      increases in FM1-43 reporting changes in membrane surface area due to cumulative
      exocytosis. Addition of glutamate, further increased the occurrence of these
      events. Statistical analysis of local FM1-43 fluorescence changes suggests that
      this is due to the recruitment of inactive exocytotic domains and due to the
      stimulation of already active exocytotic domains.

PMID- 16293248
TI  - Combining nucleoside analogues to achieve recognition of oligopurine tracts by
      triplex-forming oligonucleotides at physiological pH.
AB  - We have used DNase I footprinting to examine DNA triple helix formation at a 12
      base pair oligopurine.oligopyrimidine sequence, using oligonucleotides that
      contain combinations of 2'-aminoethoxy-5-(3-aminoprop-1-ynyl)uridine (bis-amino
      U, BAU) and 3-methyl-2-aminopyridine (MeP) in place of T and C, respectively.
      This combination acts cooperatively to enable high affinity triple helix
      formation at physiological pH. The affinity depends on the number of
      substitutions and their arrangement; oligonucleotides in which these analogues
      are evenly distributed throughout the third strand bind much better than those in
      which they are clustered together.

PMID- 16293250
TI  - TAK1-mediated transcriptional activation of CD28-responsive element and AP-1
      binding site within the IL-2 promoter in Jurkat T cells.
AB  - We focused on the functional involvement of transforming growth factor-beta
      activated kinase 1 (TAK1) in transcriptional regulation of interleukin-2 (IL-2)
      in T cells. Costimulation of Jurkat cells with 12-O-tetradecanoylphorbol-13
      acetate and A23187 leads to a rapid phosphorylation of TAK1 and TAK1-binding
      protein 1 (TAB1), critical for TAK1 activation. A specific inhibitor of TAK1
      blocked production of IL-2. In addition, overexpression of TAK1 and TAB1 induced
      secretion of IL-2. CD28-responsive element/activator protein-1-binding site
      (RE/AP) within the IL-2 promoter was a functional target for TAK1. The RE/AP
      driven transcription was regulated by TAK1-mediated activation of the c-Jun NH2
      terminal kinase, p38 and IkappaB kinase. These results indicate that TAK1 plays a
      critical role in T cell activation by controlling production of IL-2.

PMID- 16293252
TI  - What factor drives the fibrillogenic association of beta-sheets?
AB  - The identification of the driving factor for fibril formation is paramount to
      understand the molecular basis of amyloidogenic disease. Recently, an atomic
      detail structure of a fibrillogenic aggregate was reported and revealed a tight
      packing of beta-sheets. However, there is not a single pair-wise interaction of
      significance between the beta-sheets, no hydrogen bond and no hydrophobic
      interaction. Instead, there is extensive burial of polar groups at the interface.
      These observations lead to the question: What factor drives the association of
      beta-sheets? This issue is addressed by combining all-atom molecular dynamics
      with an implicit-solvent analysis. The driving force for the association arises
      from the mechanical equivalent of the dehydration propensity of pre-formed intra
      sheet hydrogen bonds and dipole-dipole interactions.

PMID- 16293251
TI  - CHIP interacts with heat shock factor 1 during heat stress.
AB  - Heat shock factor 1 (HSF1) is a major transactivator of heat shock genes in
      response to stress and mediates cell protection against various harmful
      conditions. In this study, we identified the interaction of CHIP (carboxyl
      terminus of the heat shock cognate protein 70-interacting protein) with the N
      terminus of HSF1. Using GST full-down assay, we found that CHIP directly
      interacts with C-terminal deleted HSF1 (a.a. 1-290) but not with full-length HSF1
      under non-stressed conditions. Interestingly, interaction of CHIP with full
      length HSF1 was induced by heat shock treatment. The structural change of HSF1
      was observed under heat stressed conditions by CD spectra. These observations
      demonstrate the direct interaction between HSF1 and CHIP and this interaction
      requires conformational change of HSF1 by heat stress.

PMID- 16293253
TI  - Structure of a halophilic nucleoside diphosphate kinase from Halobacterium
      salinarum.
AB  - Nucleoside diphosphate kinase from the halophilic archaeon Halobacterium
      salinarum was crystallized in a free state and a substrate-bound form with CDP.
      The structures were solved to a resolution of 2.35 and 2.2A, respectively.
      Crystals with the apo-form were obtained with His6-tagged enzyme, whereas the
      untagged form was used for co-crystallization with the nucleotide. Crosslinking
      under different salt and pH conditions revealed a stronger oligomerization
      tendency for the tagged protein at low and high salt concentrations. The
      influence of the His6-tag on the halophilic nature of the enzyme is discussed on
      the basis of the observed structural properties.

PMID- 16293254
TI  - Chiral bias of amyloid fibrils revealed by the twisted conformation of Thioflavin
      T: an induced circular dichroism/DFT study.
AB  - Since it was implicated in a number of neurodegenerative conditions, such as
      Alzheimer disease, formation of beta-sheet-rich protein fibrils (amyloids) has
      been drawing a lot of attention. One of elusive aspects of amyloidogenesis
      concerns the mechanisms of specific binding of molecules such as Congo red, or
      Thioflavin T by amyloid fibrils. A comprehensive understanding of these docking
      interactions is needed, however, for the sake of furthering biochemical studies
      and developing molecular, pharmacological strategies preventing proliferation of
      amyloids in vivo. Through the application of circular dichroism, here we show
      that upon binding to insulin fibrils, a twisted conformation is enforced in
      molecules of Thioflavin T, manifested in a strong negative Cotton effect around
      450 nm, which is supported by density functional theory-based calculations. This
      finding may lead to circular dichroism of Thioflavin T becoming a new diagnostic
      technique for protein fibrils, complementary to fluorescence spectroscopy.

PMID- 16293255
TI  - Short photoperiod influences energy intake and serum leptin level in Brandt's
      voles (Microtus brandtii).
AB  - Photoperiod cues play important roles in the regulation of seasonal variations in
      body mass (BM) and energy balance for many small mammals. The present study was
      designed to examine the effects of photoperiod acclimation on BM, energy intake,
      and serum leptin levels in Brandt's voles (Microtus (Lasiopodomys) brandtii).
      After 4 weeks of acclimation to either long (LD; light:dark, 16:8) or short (SD;
      8:16) photoperiod, SD voles had lower BM, body fat mass, and dry mass of liver
      and kidneys, but higher digestible energy intake in comparison to LD voles. SD
      voles also showed a lower level of serum leptin than did LD voles. Furthermore,
      the level of serum leptin was correlated positively with body fat mass and
      negatively with gross energy intake. Together, these data suggest that Brandt's
      voles employ a strategy of minimizing body growth, increasing energy intake, and
      mobilizing fat deposition in response to cues associated with short photoperiod.
      Furthermore, leptin seems to be involved in the regulation of BM and energy
      balance mediated by photoperiod.

PMID- 16293256
TI  - Primary prevention of coronary artery disease among middle aged men in Prague:
      twenty-year follow-up results.
AB  - BACKGROUND: Coronary artery disease (CAD) represents the most common cause of
      morbidity and mortality in the Czech Republic. The aim of this study is to
      analyze long-term cardiovascular diseases (CVD) mortality, identify predictors of
      outcome and to validate the Framingham risk function in men from the Czech
      Republic. DESIGN AND METHODS: A 20-year primary prevention study of
      atherosclerosis risk factors in 1417 men from Prague aged 38-53 years was
      launched in 1975 (STULONG). RESULTS: When analyzing CVD mortality, heavy smokers
      had hazard higher than non-smokers and light smokers (p < 0.0001); hypertensives
      higher than normotensives (p < 0.0001); men with hypercholesterolemia higher than
      those with normal cholesterol (p = 0.0432), and university-educated men lower
      than elementary-educated men (p = 0.0006). In 1980-1984, the age specific
      mortality from CVD in men from STULONG was higher (p = 0.0132) than in the Czech
      Republic, in 1985-1994 insignificantly lower. The Framingham risk function
      underestimated the absolute 10-year risk of CAD across the quintile of the risk
      (p < 0.0001), with 63% discrimination. CONCLUSION: In STULONG, the mortality from
      CVD was significantly associated with known risk factors (hypertension, smoking,
      hypercholesterolemia, education); the Framingham risk function underestimated the
      absolute 10-year risk of CAD.

PMID- 16293258
TI  - Ultrasound measurements of gastrocnemius tendon and aponeurosis lengthening in
      isometric maximal voluntary contractions.

PMID- 16293257
TI  - A survey of formal methods for determining the centre of rotation of ball joints.
AB  - The determination of an accurate centre of rotation (CoR) from segment marker
      positions is of interest across a wide range of applications, but particularly
      for clinical gait analysis and for estimating the hip joint centre during
      surgical intervention of the knee, for limb alignment purposes. For the first
      time in this survey of formal methods, we classify, analyse and compare different
      methods (geometric, algebraic, bias compensated algebraic, and Pratt sphere fit
      methods, as well as the centre transformation technique, the Holzreiter approach,
      the helical pivot technique, the Schwartz transformation techniques, the minimal
      amplitude point method and the Stoddart approach) for the determination of
      spherical joint centres from marker position data. In addition, we propose a new
      method, the symmetrical CoR estimation or SCoRE, in which the coordinates of the
      joint centre must only remain constant relative to each segment, thus not
      requiring the assumption that one segment should remain at rest. For each method,
      1000 CoR estimations were analysed with the application of isotropic, independent
      and identically distributed Gaussian noise (standard deviation 0.1cm) to each of
      the marker positions, to all markers on the segment simultaneously and the two in
      combination. For the test conditions used here, most techniques were capable of
      determining the CoR to within 0.3 cm, as long as the spherical range of motion
      (RoM) of the joint was 45 degrees or more. Under the most stringent conditions
      tested, however, the SCoRE was capable of best determining the CoR, to within
      approximately 1.2mm with a RoM of 20 degrees . The correct selection and
      application of these methodologies should help improve the accuracy of surgical
      navigation and clinical kinematic measurement.

PMID- 16293259
TI  - Mass and charge balance in self-assembled multilayer films on gold. Measurements
      with optical reflectometry and quartz crystal microbalance.
AB  - This work aimed to the determination of weight uptakes and charge balance in the
      course of successive deposition of polyelectrolytes, using the so-called self
      assembled multilayer technique. Polyelectrolytes were the quaternized
      polydimethylaminoethyl methacrylate chloride, (MADQUAT) and poly(acrylic acid)
      (PAA). Experiments were made at pH 5.5 in NaCl solutions between 10(-3) and 10(
      1) M. Deposits (5 bilayers) on a gold substrate were monitored using a quartz
      crystal microbalance (QCM) and optical fixed-angle reflectometry. Analysis of
      data lead to the determination of the sensitivity factor of the reflectometric
      output. QCM allowed the direct measurement of weight uptakes in 10(-3) and 10(-2)
      M solutions, while the viscoelastic properties of the film did not look
      appropriate for the measurement in 10(-1) M solutions. The layer-by-layer uptakes
      and charge balances in 10(-3) and 10(-2) M solutions revealed a large
      contribution of the counterions in the neutralization of the electrical charge in
      the film, more so for the highly charged MADQUAT polymer. The difference between
      two successive polymer charge densities increased significantly with the layer
      number and the electrolyte concentration. The increase of NaCl concentration
      induced an increase of MADQUAT but reversely a decrease of PAA deposits. The
      results were consistent with the determining influence of the salt in
      polyelectrolyte adsorption, both with regards to the concentration and the type
      of ions that has been well demonstrated in the literature. This work also draws
      attention to the role of small ions in the structural and application properties
      of self-assembled multilayer films.

PMID- 16293260
TI  - A hybrid rheological model for particulate suspension in zeolite crystal growth.
AB  - A hybrid constitutive model is developed to represent the thixotropic behavior of
      particulate suspension during zeolite crystallization from solution. This model
      is valid over the complete solid fraction range typical for such a process. It
      employs two internal variables, agglomeration and contiguity, to describe the
      degree to which the gel particles form short- and long-range networks. The
      contiguity is used to weigh the effects of hydrodynamic to chain-like network
      deformation on the suspension viscosity. Heterogeneous nucleation and surface
      reaction-controlled crystal growth are assumed to describe the evolution of
      microstructure and solid fraction of gel and crystals. Such a model successfully
      captures the thixotropic behavior of zeolite particulate suspension by comparison
      of the predictions with a set of experimental data.

PMID- 16293261
TI  - Working memory in children with reading disabilities.
AB  - This study investigated associations between working memory (measured by complex
      memory tasks) and both reading and mathematics abilities, as well as the possible
      mediating factors of fluid intelligence, verbal abilities, short-term memory
      (STM), and phonological awareness, in a sample of 46 6- to 11-year-olds with
      reading disabilities. As a whole, the sample was characterized by deficits in
      complex memory and visuospatial STM and by low IQ scores; language, phonological
      STM, and phonological awareness abilities fell in the low average range. Severity
      of reading difficulties within the sample was significantly associated with
      complex memory, language, and phonological awareness abilities, whereas poor
      mathematics abilities were linked with complex memory, phonological STM, and
      phonological awareness scores. These findings suggest that working memory skills
      indexed by complex memory tasks represent an important constraint on the
      acquisition of skill and knowledge in reading and mathematics. Possible
      mechanisms for the contribution of working memory to learning, and the
      implications for educational practice, are considered.

PMID- 16293262
TI  - Leaf miner-induced changes in leaf transmittance cause variations in insect
      respiration rates.
AB  - Very little is known about alterations in microclimate when an herbivore feeds on
      host plant. Modifications of leaf transmittance properties induced by feeding
      activity of the leaf miner Phyllonorycter blancardella F. were measured using a
      spectrometer. Their effects on the herbivore's body temperature and respiration
      rate have been determined under controlled conditions and varying radiation level
      employing an infrared gas analyser. By feeding within leaf tissues, a miner
      induces the formation of feeding windows which transmit a large portion of
      incoming radiations within a mine. As a result, body temperature and respiration
      rate increase with radiation level when positioned below feeding windows.
      Therefore, the miner is not always protected from radiations despite living
      within plant tissues. The amount of CO(2) released by larvae below feeding
      windows at high radiation levels is about five-fold that recorded in the dark. By
      contrast, body temperature and respiration rate increase only slightly with
      radiation level when the insect is positioned below intact tissues through which
      radiation is only weakly transmitted. A mine offers its inhabitant a
      heterogeneous light environment that allows the insect larva to thermoregulate
      through behavioural modification. Our results highlight the importance of
      physical feedbacks induced by herbivory which alter significantly an insect's
      metabolism independently of its nutritional state.

PMID- 16293264
TI  - When should signals of submission be given?-A game theory model.
AB  - During contests, losing animals often show signals communicating submission. From
      an evolutionary viewpoint, however, it is not so obvious why the losing
      individual gives such a signal instead of running away and why the winning
      individual accepts the signal instead of inflicting more severe damage. We
      investigated factors influencing the evolution of signals of submission using a
      numerical ESS model. The present analysis reveals that there is much space for
      the evolution of signals of submission, even when the winner of an escalated
      contest gets some extra benefit. In most cases, signals of submission are given
      by animals which are slightly or moderately weaker than the opponent. Signals of
      submission are expected to occur frequently (1) when the value of contested
      resource does not differ greatly from the cost of injury, (2) when the extra
      benefit of winning an escalated contest is small, (3) when the opportunity for
      safe retreat by the losing animal is small, and (4) when the estimation of the
      difference in the resource holding potential (RHP) between the combatants is
      accurate but not perfect.

PMID- 16293263
TI  - Panic attack symptom dimensions and their relationship to illness characteristics
      in panic disorder.
AB  - Subtyping panic disorder by predominant symptom constellations, such as cognitive
      or respiratory, has been done for some time, but criteria have varied
      considerably between studies. We sought to identify statistically symptom
      dimensions from intensity ratings of 13 DSM-IV panic symptoms in 343 panic
      patients interviewed with the Anxiety Disorders Interview Schedule for DSM-IV
      Lifetime Version. We then explored the relation of symptom dimensions to selected
      illness characteristics. Ratings were submitted to exploratory maximum likelihood
      factor analysis with a Promax rotation. A three-factor solution was found to
      account best for the variance. Symptoms loading highest on the first factor were
      palpitations, shortness of breath, choking, chest pain, and numbness, which
      define a cardio-respiratory type (with fear of dying). Symptoms loading highest
      on the second factor were sweating, trembling, nausea, chills/hot flashes, and
      dizziness, which defines a mixed somatic subtype. Symptoms loading highest on the
      third factor were feeling of unreality, fear of going crazy, and fear of losing
      control, which defines a cognitive subtype. Subscales based on these factors
      showed moderate intercorrelations. In a series of hierarchical multiple
      regression analyses, the cardio-respiratory subscale was a strong predictor of
      panic severity, frequency of panic attacks, and agoraphobic avoidance, while the
      cognitive subscale mostly predicted worry due to panic. In addition, patients
      with comorbid asthma had higher scores on the cardio-respiratory subscale. We
      conclude that partly independent panic symptom dimensions can be identified that
      have different implications for severity and control of panic disorder.

PMID- 16293265
TI  - Ceramide-induced preconditioning involves reactive oxygen species.
AB  - INTRODUCTION: Ceramide induces programmed cell death and it is thought to
      contribute to cardiac ischemia/reperfusion (I/R) injury. In contrast, we have
      demonstrated that administration of low doses of ceramide engenders cardiac
      preconditioning (PC). Ceramide is known to generate reactive oxygen species (ROS)
      in cells. Since mechanisms triggering the ceramide-induced cardioprotection
      remain unknown, we investigated the role of ROS in the genesis of this protective
      mechanism. METHODS: Using an isolated Langendorff-perfused rat heart model, four
      groups (n > or = 6 in each group) were considered: Control hearts underwent 30
      min index regional ischemia and 120 min of reperfusion. In the ceramide group,
      hearts were preconditioned with c2-ceramide 1 microM for 7 min followed by 10 min
      washout prior to the I/R insult. In additional groups, MPG (1 mM), a synthetic
      antioxidant was given for 15 min alone or bracketing the ceramide perfusion. In
      each group, infarct size was determined at the end of the reperfusion period and
      superoxide dismutases (CuZnSOD and MnSOD) and catalase activities were evaluated.
      RESULTS: Ceramide preconditioning reduced the infarct/area at risk (I/AAR) ratio
      (8.3 +/- 1.1% for ceramide vs. 36.4 +/- 1.2% for control, p < 0.001). Perfusion
      with MPG abolished the preconditioning effect of ceramide (I/AAR ratio = 36.7 +/-
      4.9%). Ceramide was also associated with a 29% and 38% increase in catalase and
      CuZnSOD activities, respectively, compared with control group. CONCLUSION:
      Production of reactive oxygen species following ceramide preconditioning of the
      ischemic-reperfused heart appears to play a role in the cardioprotective effect
      of ceramide.

PMID- 16293266
TI  - Determination of HBCD, PBDEs and MeO-BDEs in California sea lions (Zalophus
      californianus) stranded between 1993 and 2003.
AB  - Blubber samples from male California sea lions (Zalphophus californianus)
      stranded between 1993 and 2003 were analyzed for 27 polybrominated diphenyl ether
      (PBDE) congeners, three isomers of hexabromocyclododecane (HBCD) and 14
      methoxylated polybrominated diphenyl ether (MeO-BDE) congeners. Total PBDEs
      ranged from 450 ng/g to 4740 ng/g wet mass and total HBCD ranged from < 0.3 ng/g
      to 12 ng/g wet mass. The concentration of HBCD increased from 0.7 ng/g to12.0
      ng/g wet mass in sea lion blubber between 1993 and 2003. However, no significant
      temporal trend was observed for any of the other brominated compounds over this
      10 year period. Only one of the 14 MeO-BDE congeners was detected in the blubber
      samples, 6-methoxy-2,2',4,4'-tetrabromodiphenyl ether (6-MeO-BDE 47), and
      concentrations ranged from < 0.2 ng/g to 12 ng/g wet mass. A bromo-, chloro
      heterocyclic compound, 1,1'-dimethyl-tetrabromo-dichloro-2,2'-bipyrrole (DBP
      Br4Cl2), previously reported in marine species along the Pacific coast, was also
      identified in the sea lion blubber. DBP-Br4Cl2 ranged from 44 ng/g wet mass to
      660 ng/g wet mass and was present at concentrations rivaling the dominant PBDE
      congener, BDE 47 (2,2',4,4'-tetrabromodiphenyl ether). Concentrations of DBP
      Br4Cl2 were positively correlated with 6-MeO-BDE 47 (r = 0.7; p < 0.05). Both of
      these compounds have been identified in marine algae and sponges, and studies
      suggest they are both produced from natural sources. This study demonstrates that
      brominated compounds from both anthropogenic and biogenic sources can accumulate
      to similar levels in marine mammals. In addition, HBCD concentrations appear to
      be increasing in California sea lion populations, whereas PBDE concentrations,
      between 1993 and 2003, were highly variable.

PMID- 16293267
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 coasts of Singapore's southern islands,
      to: (1) quantitatively assess and compare coral community composition and
      structure, and recruitment rates, (2) assess the relationship between the
      aforementioned patterns and the environmental conditions, and (3) provide
      insights on potential processes that incorporate history at these study sites.
      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)year(-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) (Recruitment rate, RR=1.51-0.17 *DFSPM)
      and water clarity (RR=3.56-2.92 *K) exhibited strong and inverse relationships
      with recruitment rates. Although measured levels of the down-ward 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- 16293268
TI  - Chemical composition and not only total surface area is important for the effects
      of ultrafine particles.

PMID- 16293269
TI  - Cellular and molecular effects for mutation induction in normal human cells
      irradiated with accelerated neon ions.
AB  - We investigated the linear energy transfer (LET) dependence of mutation induction
      on the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in normal
      human fibroblast-like cells irradiated with accelerated neon-ion beams. The cells
      were irradiated with neon-ion beams at various LETs ranging from 63 to 335
      keV/microm. Neon-ion beams were accelerated by the Riken Ring Cyclotron at the
      Institute of Physical and Chemical Research in Japan. Mutation induction at the
      HPRT locus was detected to measure 6-thioguanine-resistant clones. The mutation
      spectrum of the deletion pattern of exons of mutants was analyzed using the
      multiplex polymerase chain reaction (PCR). The dose-response curves increased
      steeply up to 0.5 Gy and leveled off or decreased between 0.5 and 1.0 Gy,
      compared to the response to (137)Cs gamma-rays. The mutation frequency increased
      up to 105 keV/microm and then there was a downward trend with increasing LET
      values. The deletion pattern of exons was non-specific. About 75-100% of the
      mutants produced using LETs ranging from 63 to 335 keV/mum showed all or partial
      deletions of exons, while among gamma-ray-induced mutants 30% showed no
      deletions, 30% partial deletions and 40% complete deletions. These results
      suggested that the dose-response curves of neon-ion-induced mutations were
      dependent upon LET values, but the deletion pattern of DNA was not.

PMID- 16293270
TI  - Red wine polyphenols influence carcinogenesis, intestinal microflora, oxidative
      damage and gene expression profiles of colonic mucosa in F344 rats.
AB  - Polyphenols from tea and other beverages such as red wine have been regarded with
      interest as possible chemopreventive agents against cancer. Here we report that
      red wine polyphenols (50 mg/kg) administered with the diet to F344 rats for 16
      weeks inhibited colon carcinogenesis induced by azoxymethane (AOM, 7.4 mg/kg,
      total dose 74 mg/kg) or dimethylhydrazine (DMH, 30 mg/kg, total dose, 300 mg/kg).
      Polyphenol-treated animals had a consistently lower tumour yield compared to
      controls. In polyphenol-treated rats, the main bacterial strains in the faeces at
      sacrifice were Bacteroides, Lactobacillus and Bifidobacterium spp., whereas
      microorganisms predominantly identified in control-fed rats were Bacteroides,
      Clostridium and Propionibacterium spp. Wine polyphenols (57 mg/kg for 10 days, by
      gavage), administered to rats not treated with carcinogens, produced a
      significant decrease in the basal level of DNA oxidative damage of the colon
      mucosa as measured with the comet assay (average pyrimidine oxidation was reduced
      by 62% and purine oxidation by 57%, p<0.05). To further explore the molecular
      effects of wine polyphenols we used the microarray technology to study gene
      expression profiles: rats were treated with 50 mg/kg wine polyphenols for 14
      days, mixed in the diet. Global expression analysis of 5707 genes revealed an
      extensive down-regulation of genes involved in a wide range of physiological
      functions, such as metabolism, transport, signal transduction and intercellular
      signalling. By analysing metabolic pathways with the GenMAPP software program we
      observed that two major regulatory pathways were down-regulated in the colon
      mucosa of polyphenols-treated rats: inflammatory response and steroid metabolism.
      We also found a down-regulation of many genes regulating cell surface antigens,
      metabolic enzymes and cellular response to oxidative stress. In conclusion,
      reduction of oxidative damage, modulation of colonic flora and variation in gene
      expression may all concur in the modulation of intestinal function and
      carcinogenesis by wine polyphenols.

PMID- 16293271
TI  - Verbal fluency deficits in multiple sclerosis.
AB  - A quantitative review of 35 studies with 3673 participants was conducted to
      estimate and compare the magnitude of deficits upon tests of phonemic and
      semantic fluency for participants with multiple sclerosis (MS) relative to
      healthy controls. Participants with MS were substantially but similarly impaired
      on tests of phonemic and semantic fluency. These deficits were larger than
      deficits on measures of verbal intelligence, confrontation naming and another
      widely used measure of executive functioning, the Wisconsin Card Sorting Test,
      but were of a comparable or smaller magnitude relative to deficits on the oral
      version of the Symbol Digit Modalities Test (SDMT). This is consistent with other
      research suggesting that measures of verbal fluency and the SDMT may be amongst
      the most sensitive neuropsychological measures to cognitive impairment in MS.
      Increased neurological disability and a chronic progressive (as opposed to a
      relapsing remitting) disease course were associated with larger deficits on tests
      of phonemic and semantic fluency. However, it is suggested that this latter
      finding is attributable to the distinct clinical features of chronic progressive
      and relapsing remitting sub-types. Thus, patients who follow a chronic
      progressive course tend to be older, have an increased duration of illness and
      experience greater neurological disability. Once these variables were controlled
      for, differences between the two sub-types were substantially attenuated.

PMID- 16293272
TI  - Selective impairment of sadness and disgust recognition in abstinent ecstasy
      users.
AB  - Previous data have suggested that ecstasy use may affect cognitive functions. The
      relationship between ecstasy use and emotion recognition remains largely unknown.
      This study reports the findings on the neuropsychological effects of ecstasy use
      on recognition of basic human emotions among 100 abstinent ecstasy users, along
      with 100 demographically matched nonusers. Recognition of both facial and
      prosodic emotions was studied. In addition, neuropsychological predictors of
      emotion recognition for abstinent ecstasy users were examined. The results showed
      that abstinent ecstasy users were impaired, relative to nonusers, on overall
      emotion recognition. In particular, recognition of sadness and disgust was
      significantly affected. The emotion-recognition deficits observed among the
      abstinent ecstasy users may reflect a complex derangement of monoamines and/or
      general degenerative change observed in the addicted populations. The length of
      time in months since ecstasy was last consumed, cumulative ecstasy dosage, and
      years of education negatively predicted various domains of emotion recognition.
      The observation that nonverbal and verbal fluency functions were significant
      predictors of emotion identification, as well as of recognition of sadness and
      disgust, suggests that the frontal executive system might be affected by ecstasy
      use.

PMID- 16293273
TI  - Microbial transformation of the sesquiterpenoid (-)-maalioxide by Mucor plumbeus.
AB  - Microbial transformation of the sesquiterpenoid (-)-maalioxide by the fungus
      Mucor plumbeus gave three metabolites, 9beta-hydroxymaalioxide, 1beta
      hydroxymaalioxide and 7beta-hydroxymaalioxide. 9beta-hydroxymaalioxide and its
      structure was established on the basis of its spectroscopic properties and
      chemical reactions.

PMID- 16293274
TI  - Chemical variation within and among six northern willow species.
AB  - Plant tissues typically contain a diverse complement of secondary metabolites
      that serve as protection against various biotic and abiotic hazards. Chemical
      similarities are commonly used to infer phylogenetic relationships among plant
      taxa, but the studies are typically based on the mean concentration of each
      compound in each study species, thus overlooking within-species variability. In
      order to investigate patterns of intra- and interspecific chemical variation in
      plants, we measured the concentrations of condensed tannins and 36 other phenolic
      compounds in 120 leaf samples representing six northern Salix species.
      Multivariate clustering and ordination analyses of the data show that: (1)
      Despite considerable within-species variation in chemical profiles, intraspecific
      variability is on average lower than the variation among species. (2)
      Interspecific similarities are sensitive to the data analysis methods used, and
      different chemical classes produce partly contradictory results. (3) Compounds
      within each biosynthetic class tend to behave in a correlated manner and,
      consequently, overall chemical similarities are weakly correlated with the
      phylogeny of the studied species. The conclusion is that chemical data are poorly
      suited for phylogenetic inference, unless methods for data analysis are improved
      to take into account the biosynthetic routes by which the compounds are produced.

PMID- 16293275
TI  - Biflavonoids from Lonicera japonica.
AB  - Two biflavonoids, 3'-O-methyl loniflavone [5,5'',7,7''-tetrahydroxy 3'-methoxy
      4',4'''-biflavonyl ether (1)] and loniflavone [5,5'',7,7'',3'-pentahydroxy
      4',4'''-biflavonyl ether (2)] along with luteolin (3) and chrysin (4) were
      isolated from the leaves of Lonicera japonica. The structures were established on
      the basis of UV/vis, 1D, 2D NMR (HMQC and HMBC) and ESI-QTOF-MS/MS spectroscopic
      methods and chemical evidences.

PMID- 16293277
TI  - Unusually sulfated and oxygenated steroids from Withania somnifera.
AB  - Four (1, 8-10) and six known (2-7) withanolides were isolated from the leaves of
      Withania somnifera. Among the new compounds, 10 possessed the rare 3-O-sulfate
      group with the saturation in A ring and 9 contained unusual 1,4-dien-3-one group.
      Compound 8 did not have usual 2,3 unsaturation in A ring while 1 had the rare C
      16 double bond. The structures of all the compounds were elucidated by
      spectroscopic methods and chemical transformation.

PMID- 16293276
TI  - Triterpenoid glycosides from Bacopa monnieri.
AB  - Two triterpenoid glycosides have been isolated along with 10 known saponins from
      Bacopa monnieri. Structures of the compounds have been elucidated as 3-O-[beta-D
      glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] jujubogenin (1) and 3-O-[beta-D
      glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] pseudojujubogenin (2) by high
      resolution NMR spectral data and chemical correlations. Further, the chemical
      compositions of bacosides A and B have been delineated.

PMID- 16293278
TI  - Failure of HIV-2 viral load assay in a severely immunodeficient patient: clinical
      and therapeutic management issues.
AB  - We report the case of an HIV-2-infected patient with severe immunosupression
      despite undetectable plasma HIV-2 RNA. This immunovirological discordance was due
      to failure of the viral load assay and infection by an unknown HIV-2 subtype.
      Treatment was probably suboptimal, leading to the selection of several resistance
      mutations and treatment failure.

PMID- 16293279
TI  - Electricity generation from swine wastewater using microbial fuel cells.
AB  - Microbial fuel cells (MFCs) represent a new method for treating animal
      wastewaters and simultaneously producing electricity. Preliminary tests using a
      two-chambered MFC with an aqueous cathode indicated that electricity could be
      generated from swine wastewater containing 8320 +/- 190 mg/L of soluble chemical
      oxygen demand (SCOD) (maximum power density of 45 mW/m2). More extensive tests
      with a single-chambered air cathode MFC produced a maximum power density with the
      animal wastewater of 261 mW/m2 (200 omega resistor), which was 79% larger than
      that previously obtained with the same system using domestic wastewater (146 +/-
      8 mW/m2) due to the higher concentration of organic matter in the swine
      wastewater. Power generation as a function of substrate concentration was modeled
      according to saturation kinetics, with a maximum power density of P(max) = 225
      mW/m2 (fixed 1000 omega resistor) and half-saturation concentration of K(s) =
      1512 mg/L (total COD). Ammonia was removed from 198 +/- 1 to 34 +/- 1 mg/L (83%
      removal). In order to try to increase power output and overall treatment
      efficiency, diluted (1:10) wastewater was sonicated and autoclaved. This
      pretreated wastewater generated 16% more power after treatment (110 +/- 4 mW/m2)
      than before treatment (96 +/- 4 mW/m2). SCOD removal was increased from 88% to
      92% by stirring diluted wastewater, although power output slightly decreased.
      These results demonstrate that animal wastewaters such as this swine wastewater
      can be used for power generation in MFCs while at the same time achieving
      wastewater treatment.

PMID- 16293280
TI  - Development of a reliable alkaline wastewater treatment process: optimization of
      the pre-treatment step.
AB  - Alkaline waters produced by caprolactam plants polymerizing the fibres of nylon-6
      are characterized by a very high alkalinity, salinity and COD values, in addition
      to the presence of recalcitrant organic molecules. These characteristics make
      alkaline wastewaters very difficult to treat; so the development of the suitable
      sequence to carry out in a depuration process appears of great interest. The
      proposed general process consists of three main steps: first, pre-treatment for
      the acidification of the polluted stream, second, a successive extraction of the
      bio-recalcitrant compound (noted as cycloexanecarboxysulphonic acid (CECS)) and a
      final biological treatment. In particular, this paper deals with the pre
      treatment step: it consists of an acidification process by means of sulphuric
      acid with the concomitant precipitation of black slurries in the presence of
      different substances, such as solvents, CaCl2, bentonite, several flocculants and
      coagulants. The aim of this study is to set an experimental procedure, which
      could minimize fouling problems during sludge filtration. The use of additives
      like bentonite seems to give the best results, because it allows good COD
      reductions and a filterable precipitate, which avoids excessive fouling problems
      of the experimental apparatus.

PMID- 16293281
TI  - Effect of heavy metals on the production of several laccase isoenzymes by
      Trametes versicolor and on their ability to decolourise dyes.
AB  - The white-rot fungus Trametes versicolor growing in submerged culture on a basal
      medium, with barley bran as a carbon source, produced two laccase isoenzymes LacI
      and LacII. The addition of metal ions to the culture medium was performed to
      improve the total laccase activity and to determine the effect on the production
      of laccase isoenzymes. From all the tested metals, only Cu2+ increased laccase
      activity (up to 12-fold with respect to control cultures) and T. versicolor in
      presence of all metals produced the two isoenzymes in different proportion with
      ratios of activity (LacI/LacII) varying between 0.11 and 0.51. This factor played
      an important role in the decolourisation of the textile dye Indigo Carmine.

PMID- 16293282
TI  - An improved UV/Fe3+ process by combination with electrocatalysis for p
      nitrophenol degradation.
AB  - p-nitrophenol (PNP) was investigated as a model pollutant under the improved
      UV/Fe3+ process by combination with electrocatalysis. In the individual UV/Fe3+
      process, PNP degradation rate was dependent on Fe(III) concentration and
      decreased during degradation due to the depletion of ferric ion and thus it was
      very difficult to reach the quick mineralization of organics. These drawbacks
      could be significantly overcome in the modified UV/Fe3+ process, and synergetic
      effects for PNP and COD removal were observed at two investigated Fe(III)
      concentrations. The enhancements on the degree of conversion for PNP and COD in
      presence of 0.5 mM Fe(III) were 184% and 242%, respectively, and PNP of initial
      concentration of 1.0 mM could be completely removed within 1 h. Thus such a
      process would be very attractive to the rapid mineralization of the biorefractory
      compounds for wastewater treatment. The possible reasons for the synergetic
      effects were the electrochemical regeneration of ferric ion and the role of the
      oxygen that formed on the anode. Based on degradation intermediates
      identification and synergetic effect probe, a general reaction pathway for PNP
      degradation in the improved process was proposed.

PMID- 16293283
TI  - Formation and instability of aerobic granules under high organic loading
      conditions.
AB  - The cultivation and instability of aerobic granular sludge in a sequencing batch
      reactor under high loading conditions were investigated. Compact bacteria
      dominated aerobic granules with a mean diameter of 1 mm were formed at a chemical
      oxygen demand (COD) loading rate of 6.0 kg m(-3) d(-1) within 30 d. However, the
      compact bacteria-dominated aerobic granules were not stable and transited to
      large-sized filamentous ones gradually. With the formation of bacteria-dominated
      granules, the hydrophobicity and specific gravity of the sludge increased. When
      the granules were transited to filamentous ones, the hydrophobicity and specific
      gravity decreased. Both granules had a high COD removal efficiency, excellent
      settling ability and showed a clear, regular round-shaped outline. After the
      filamentous granules reached a diameter of 16 mm, due to the mass transfer
      limitation and the possible presence of anaerobes in the inner part of the
      granules, they began to disintegrate and be washed out of the reactor, follow by
      failure of the reactor.

PMID- 16293284
TI  - Probabilistic risk assessment for personal exposure to carcinogenic polycyclic
      aromatic hydrocarbons in Taiwanese temples.
AB  - To assess how the human exposure to airborne carcinogenic polycyclic aromatic
      hydrocarbons (PAHs) during working in or visiting a typical Taiwanese temple, we
      present a probabilistic risk model, appraised with reported empirical data. Two
      approaches are applied, one based on animal-derived benzo[a]pyrene (B[a]P) toxic
      equivalents (B[a]P(eq)) of individual PAHs and one is assumed that the potency of
      PAH mixtures is linked to their B[a]P level. The model integrates probabilistic
      exposure profiles of total-PAH and particle-bound PAH levels inside a temple from
      a published exploratory study with probabilistic incremental lifetime cancer risk
      (ILCR) models taking into account inhalation and dermal contact pathways, to
      quantitatively estimate the exposure risks for three age groups of adult,
      adolescent, and child. Risk analysis indicates that 90% probability inhalation
      ILCRs for three age groups have orders of magnitude around 10(-7)--10(-6);
      whereas for the dermal contact ILCRs ranging from 10(-5) to 10(-4), indicating
      high potential cancer risk. All 90% probabilities of B[a]P- and B[a]P(eq)-based
      total ILCRs are larger than 10(-6), indicating unacceptable probability
      distributions for three age groups. Sensitivity analysis indicates that to
      increase the accuracy of the results efforts should focus on a better definition
      of probability distributions for inhalation cancer slope factor, inhalation
      rates, and particle-bound PAH-to-skin adherence factor. We estimate risk-based
      visiting frequency advice for adult, adolescent, and child to a temple ranging
      from 5 to 7, 17 to 23, and 48 to 65 year(-1), respectively, based on an average
      3h residence time.

PMID- 16293285
TI  - Methyl parathion toxicity to and removal efficiency by Typha latifolia in water
      and artificial sediments.
AB  - Methyl parathion (MeP) is a very hazardous pesticide freely used in agriculture
      in Mexico. This pesticide and others, arriving through different processes, exert
      significant effects on water quality with serious consequences for environmental
      and human health. This study evaluates the removal efficiency of common cattail
      Typha latifolia L. on MeP in water and artificial sediments. The effects of the
      pesticide on this macrophyte after 10 days of exposure were determined using a
      concentration range of 0-200 mg l(-1), 198.1+/-1.79 g average biomass, pH 7.0, 18
      22 degrees C temperature and natural daylight/darkness periods, using chlorophyll
      production as a biomarker. Removal kinetics were conducted under similar
      conditions on days 0, 3, 7, 9, 11 and 14 of exposure, using 6 mg l(-1) in each
      system. Pesticide concentration, chlorophyll content and glutathione S
      transferase (GST) activity were quantified. Results show a high removal
      efficiency of cattails on MeP in water and sediments relative to controls. An
      increase in GST activity and a decline in chlorophyll content in the test systems
      were not significantly different relative to controls. Cattails may thus be a
      good candidate for development of a phytoremediation system for MeP-contaminated
      water and artificial sediments.

PMID- 16293286
TI  - An ultrasonic assisted extraction method to release heavy metals from untreated
      sewage sludge samples.
AB  - A rapid ultrasound accelerated sequential extraction procedure has been used to
      develop sequential extraction proposed by BCR protocol (the community Bureau of
      Reference now the European Union "Measurement and Testing Programme"). The
      effects of the ultrasonic treatment on the extraction of Cu, Cd, Cr, Pb, Ni and
      Zn from untreated sewage sludge collected from industrial site of Hyderabad city
      (Pakistan) were compared with those obtained from conventional sequentional
      extraction procedure of modified BCR protocol. In BCR method, each extraction
      steps takes 10h, where as with the use of compromise sonication conditions in
      ultrasonic bath, steps 1-3 of the sequential extraction (excluding the hydrogen
      peroxide digestion in step 3, which was not performed with sonication) could be
      completed in 30, 30 and 30 min, respectively. Extractable Cd, Cr, Pb and Ni
      contents were obtained by both comparable methodologies were measured by
      electrothermal atomic absorption spectrometry (ETAAS), while for Cu and Zn Flame
      atomic absorption spectrometry (FAAS) was used. The validations of both methods
      were compared by the analysis of certified reference material of soil amended
      with sewage sludge (BCR 483). According to statistical evaluation of the results,
      the proposed accelerated extraction method is valid alternative to conventional
      shaking with much shorter extraction time with p value <0.05. The overall metal
      recoveries in steps 1-3 (excluding residual step) were 95-100% of those obtained
      with the conventional BCR protocol, except for Cu extracted (91.6%) as related to
      indicative values of Cu in BCR 483 obtained in 1-3 steps. The results of the
      partitioning study of untreated industrial waste water sewage sludge, indicate
      that more easily mobilized forms (acid exchangeable) were predominant for Cd and
      Zn, in contrast, the largest amount of Pb and Cr was associated with the
      iron/manganese oxide and organic matter/sulphide fractions.

PMID- 16293287
TI  - Status of journal: DOs and DON'Ts.

PMID- 16293288
TI  - Combined chemical and biological treatment of oil contaminated soil.
AB  - Combined chemical (Fenton-like and ozonation) and biological treatment for the
      remediation of shale oil and transformer oil contaminated soil has been under
      study. Chemical treatment of shale oil and transformer oil adsorbed in peat
      resulted in lower contaminants' removal and required higher addition of chemicals
      than chemical treatment of contaminants in sand matrix. The acidic pH (3.0)
      conditions favoured Fenton-like oxidation of oil in soil. Nevertheless, it was
      concluded that remediation of contaminated soil using in situ Fenton-like
      treatment will be more feasible at natural soil pH. Both investigated chemical
      processes (Fenton-like and ozonation) allowed improving the subsequent
      biodegradability of oil. Moderate doses of chemical oxidants (hydrogen peroxide,
      ozone) should be applied in combination of chemical treatment (both, Fenton-like
      or ozonation) and biotreatment. For remediation of transformer oil and shale oil
      contaminated soil Fenton-like pre-treatment followed by biodegradation was found
      to be the most efficient.

PMID- 16293289
TI  - Complexes of fulvic acid on the surface of hematite, goethite, and akaganeite:
      FTIR observation.
AB  - The present work extended our knowledge on the binding and complexation of a
      fulvic acid (FA) derived from leonardite and the iron oxides (hematite, goethite
      and akaganeite) by Fourier transform infrared spectroscopy (FTIR). As a
      prerequisite, the iron oxides were firstly prepared and characterized by
      transmission electron micrograph (TEM). All iron phases were single and well
      described crystalloid. The FTIR data obtained by two different sampling
      preparation methods gave the consisting evidences that under our experimental
      conditions the interaction mechanism was to the ligand-exchange involving
      carboxylic functional groups of the FA and the surfaces sites of both hematite
      and goethite, while no complexation can be evidenced in the case of akaganeite,
      only surface adsorption. In general, the binding affinities of the iron oxides
      with the FA was in the order of hematite>goethite>akaganeite. The present method,
      although associated with some uncertainties, provided an opportunity to increase
      the knowledge in the field of the humic chemistry.

PMID- 16293290
TI  - Bioaccumulation, depuration and oxidative stress in fish Carassius auratus under
      phenanthrene exposure.
AB  - In this study, laboratory experiment was carried out to determine phenanthrene
      bioaccumulation, depuration in whole fish and oxidative stress in the liver of
      freshwater fish Carassius auratus. Fish were exposed to 0.05 mg/l phenanthrene
      for different periods, while one control group was designated for each exposure
      group. Some fish after 7 days of exposure were transferred to diluted water. The
      concentrations of phenanthrene in fish were analyzed by HPLC. Twenty-four hours
      after the exposure, reactive oxygen species (ROS) were trapped by phenyl-tert
      butylnitrone and detected by electron paramagnetic resonance (EPR). The
      activities of superoxide dismutase (SOD), catalase (CAT), and glutathione-s
      transferase (GST) were also determined. The concentrations of phenanthrene in
      fish increased rapidly shortly after the start of the exposure, reached a maximum
      level at the 2 days, and then it declined quickly to low-level-steady state. The
      elimination process of phenanthrene could be divided into two periods-a fast
      elimination period following a slower loss period. The elimination curve could be
      fitted mathematically as the sum of two exponential functions according to two
      compartment model: C(t)=2.72e(-1.065t) + 0.68e(-0.0364t). The PBN-radical adducts
      were detected in fish liver samples following the exposure 24h. The hyperfine
      splitting constants for the PBN-radical adducts were aN = 13.5 G, aH = 1.77 G and
      g value was 2.0058, which were consistent with those of PBN/()OH. The results
      indicated that the hydroxyl radical was probably significantly induced during the
      exposure of phenanthrene, as compared to the control group. The changes of
      activities of the antioxidant enzymes also were observed. In addition, after fish
      were removed from phenanthrene exposure, the recovery status of these antioxidant
      indices was explored. These results clearly indicated phenanthrene could be
      accumulated in fish and similar redox cyclings were produced, resulting in the
      changes of the activities of the antioxidant enzymes and the production of ROS
      with the oxidative stress.

PMID- 16293291
TI  - Mercury bioaccumulation and phytotoxicity in two wild plant species of Almaden
      area.
AB  - Mercury is a widely distributed environmental pollutant, able to induce toxicity
      in living organisms, including higher plants. Some plant species are able to grow
      in mine sites, like the Almaden zone in Spain. Our study focus on two of these
      plant species, Rumex induratus and Marrubium vulgare and their responses to
      natural Hg exposure. Total Hg concentration in the soil below the plants could be
      classified as toxic, although the available fraction was low. Hg availability was
      higher for the M. vulgare than for the R. induratus plot. Hg concentrations in
      field plants of R. induratus and M. vulgare grown on these soils can be
      considered as phytotoxic, although no symptoms of Hg toxicity were observed in
      any of them. According to the BAF ([Hg](tissue)/[Hg](avail)), R. induratus showed
      a higher ability in Hg uptake and translocation to shoots, as well as higher
      concentrations of MDA and -SH:Hg ratios, so that this plant is more sensitive to
      Hg than M. vulgare. The resistance to Hg and the capability to extract Hg from
      the soil make both M. vulgare and R. induratus good candidates for Hg
      phytoremediation of contaminated soils.

PMID- 16293292
TI  - A comparison of contaminant dynamics in arctic and temperate fish: A modeling
      approach.
AB  - In order to compare the abilities of arctic and temperate fish to accumulate PCBs
      we conduct a metabolic analysis to determine how process rates in a mathematical
      fish contaminant model change with temperature. We evaluate the model by applying
      the original and adapted models to estimate PCB concentrations in lake trout
      (Salvelinus namaycush) in Trout Lake, Ontario, Canada, and in arctic char
      (Salvelinus alphinus) in Lake Oyangen, in the Norwegian high arctic. Modeled
      concentrations are, for the most part, within 50% of mean measured values and are
      comparable to the error associated with the fish data. In order to evaluate
      differences in fish bioaccumulation processes, the model is applied to
      hypothetical arctic and temperate systems, assuming the same contaminant input
      values in water and diet. The model predicts that temperate salmonids are able to
      biomagnify PCBs 6-60% more than arctic salmonids. For all congeners, the lower
      BMF(MAX) of arctic fish contribute to their lower concentrations. For congeners
      with log K(ow) < 6.0, the lower concentrations in arctic fish are also attributed
      to faster loss due to gill ventilation. Faster growth rates for temperate fish
      reduce the difference in bioaccumulation for congeners with log K(ow) > 7.0.
      These processes are controlled by the influence of lipid in the fish and their
      diet as well as the dependence of growth on temperature. We suggest that fish
      models originally calibrated for temperate systems may be directly applied to
      arctic lakes after accounting for the lipid content of the fish and their diet as
      well as water temperature.

PMID- 16293293
TI  - The aquatic toxicity of anionic surfactants to Daphnia magna--a comparative QSAR
      study of linear alkylbenzene sulphonates and ester sulphonates.
AB  - This paper develops quantitative structure activity relationships (QSARs) for the
      acute aquatic toxicity of the anionic surfactants linear alkylbenzene sulphonates
      (LAS) and ester sulphonates (ES) to Daphnia magna, the aim being to investigate
      the modes of action by comparing the QSARs for the two types of surfactant. The
      generated data for ES have been used to develop a QSAR correlating toxicity with
      calculated log P values: log(1/EC50)= 0.78 log P+1.37. This equation has an
      intercept 1.1 log units lower than a QSAR for linear alkylbenzene sulphonates
      (LAS). The findings suggest that either ES surfactants act by a different mode of
      action to LAS and other anionic surfactants or the log P calculation method
      introduces a systematic overestimate when applied to ES.

PMID- 16293295
TI  - Animal models of cognitive dysfunction.
AB  - The increased life expectancy in industrialised countries in the last half
      century has also brought to a greater incidence of neurological disorders,
      including neurodegenerative diseases and developing in a rather long time. In
      this respect, Alzheimer's disease (AD), for the large incidence, and the dramatic
      loss of autonomy caused by its cognitive and behavioural symptoms represents one
      of the main challenges of modern medicine. Although AD is a typical human disease
      and probably includes several nosographic entities, the use of animal models may
      contribute to understand specific aspects of pathophysiology of the disease. The
      most widely used animal models are rodents and non-human primates. In this review
      different animal models characterised by impaired cognitive functions are
      analysed. None of the models available mimics exactly cognitive, behavioural,
      biochemical and histopathological abnormalities observed in neurological
      disorders characterised by cognitive impairment. However, partial reproduction of
      neuropathology and/or cognitive deficits of Alzheimer's disease (AD), vascular
      dementia and dementia occurring in Huntington's and Parkinson's diseases, or in
      other neurodegenerative disorders may represent a basis for understanding
      pathophysiological traits of these diseases and for contributing to their
      treatments.

PMID- 16293294
TI  - Muscarinic cholinergic receptor subtypes in cerebral cortex of Fisher 344 rats: a
      light microscope autoradiography study of age-related changes.
AB  - The density and localization of muscarinic cholinergic M1-M5 receptor subtypes
      was investigated in frontal and occipital cortex of male Fisher 344 rats aged 6
      months (young-adult), 15 months (mature) and 22 months (senescent) by combined
      kinetic and equilibrium binding and light microscope autoradiography. In 6-month
      old rats, the rank order density of muscarinic cholinergic receptor subtypes was
      M1>M2>M4>M3>M5 both in frontal and occipital cortex. A not homogeneous
      distribution of different receptor subtypes throughout cerebrocortical layers of
      frontal or occipital cortex was found. In frontal cortex silver grains
      corresponding to the M1 and M2 receptor subtypes were decreased in 15- and 22
      month-old groups. The M3 receptor density was remarkably and moderately decreased
      in layers II/III and V, respectively, of rats aged 15 and 22 months. A reduced M4
      receptor density was observed in layer I and to a lesser extent in layer V of
      mature and senescent rats, whereas no age-related changes of M5 receptor were
      found. In occipital cortex a diminution of M1 receptor was observed in layers
      II/III and V of mature and senescent rats. The M2 receptor expression decreased
      in layer I of 15- and 22-month-old senescent rats, whereas M3-M5 receptors were
      unchanged with exception of a slight decrease of the M4 receptor in layer IV and
      of M5 receptor in layers II/III. These findings indicate a different sensitivity
      to aging of muscarinic receptor subtypes located in various cerebrocortical
      layers. This may account for the difficulty in obtaining relevant results in
      manipulating cholinoceptors to counter age-related impairment of cholinergic
      system.

PMID- 16293296
TI  - Proteome studies of CSF in AD patients.
AB  - Proteins in cerebrospinal fluid (CSF) may often serve as indicators of
      neurodegenerative diseases, and are a rich source for biomarker discovery.
      However, a large dynamic range of proteins in CSF makes the analysis very
      challenging because high abundant proteins tend to mask those of lower abundance.
      Therefore, advances in the proteomic analysis had to be applied in the screen for
      new specific biomarkers for Alzheimer's disease (AD). In this study, we have
      summarised the studies regarding two-dimensional gel electrophoresis (2-DE), and
      surface enhanced laser desorption/ionisation mass spectrometry (SELDI) technology
      that have been used in CSF of AD patients. Many proteins have shown to be altered
      in CSF of AD patients compared to controls, by using a protein pattern, from 2-D
      gel analysis or from SELDI analysis. Several studies show that the use of a panel
      of biomarkers derived from proteomic analysis is an advantageous way to
      distinguish AD from normal, and other dementia subjects.

PMID- 16293298
TI  - Spatial variations of mercury in sediment of Minamata Bay, Japan.
AB  - Mercury-contaminated effluent was discharged into Minamata Bay from a chemical
      plant over a period of approximately 40 years until 1968. In October 1977, the
      Minamata Bay Pollution Prevention Project was initiated to dispose of sedimentary
      sludge containing mercury concentrations higher than 25 mg kg(-1). In March 1990,
      the project was completed. In an effort to estimate current contamination in the
      bay, the vertical and horizontal distributions of mercury in sediment were
      investigated. Sediment core samples were collected on June 26, 2002 at 16
      locations in Minamata Bay and Fukuro Bay located in the southern part of Minamata
      Bay. The sediment in Fukuro Bay had not been dredged. The total mercury
      concentration in surface sediment was 1.4-4.3 mg kg(-1) (2.9+/-0.9 mg kg(-1),
      n=9) for the dredged area of Minamata Bay and 0.3-4.8 mg kg(-1) (3.6+/-1.6 mg kg(
      1), n=4) for Fukuro Bay. In the lower layers of long cores taken from both areas,
      the total mercury concentration decreased with depth and finally showed
      relatively uniform low values. These values can be considered to represent the
      background concentration absent of anthropogenic influence, which was estimated
      for the study area to be 0.068+/-0.012 mg kg(-1) (n=10). From the surface, the
      total mercury concentration in Fukuro Bay increased with depth and reached a
      maximum at 8-14 cm. In Minamata Bay, several centimeters from the surface the
      total mercury concentration did not change significantly having considerably
      higher values than the background level. At six stations, the methylmercury
      concentration was determined. Although the vertical variations were similar to
      those for total mercury, Fukuro Bay sediment showed a higher concentration of
      methylmercury than Minamata Bay sediment.

PMID- 16293299
TI  - The timing of ovulation and insemination schedules in superstimulated cattle.
AB  - The development of treatments that control follicular wave dynamics during the
      bovine estrous cycle has resulted in interesting possibilities for the precise
      control of follicular wave emergence and the time of ovulation. For
      superstimulation, follicular wave emergence can be controlled by ultrasound
      guided follicle ablation with FSH treatments initiated 1 or 2 d later, or
      injection of estradiol combined with progesterone at the time of insertion of a
      progestogen releasing device and FSH treatments beginning 4 d later. These are
      the most widely used protocols for superstimulation of donor cows because they
      offer the convenience of being able to initiate treatments quickly and at a self
      appointed time, without reducing the number of transferable embryos. However,
      these protocols still require precise estrus detection of donors following
      superstimulation in order to conduct AI at the most appropriate time. Recent
      studies have been designed to develop superstimulation protocols that involve
      fixed-time AI of donors, without regard to estrus detection. Results presented
      herein indicate that delaying the removal of a progestogen releasing device,
      combined with the administration of GnRH or porcine LH (pLH) 12 or 24 h later
      results in predictable, synchronous ovulations, permitting fixed-time AI without
      reducing the numbers or quality of embryos. These protocols facilitate the
      application of on-farm embryo transfer programs because they are practical, easy
      to administer by farm personnel, and more importantly, they eliminate the need
      for detecting estrus.

PMID- 16293300
TI  - Particles of liquid-crystalline dispersions formed by (nucleic acid-rare earth
      element) complexes as a potential platform for neutron capture therapy.
AB  - Microscopic size particles of the cholesteric double-stranded DNA (RNA) liquid
      crystalline dispersions, containing the ions of the rare earth elements in their
      content, have been obtained for the first time. The properties of these particles
      differ from those of classical DNA cholesterics noticeably. The local
      concentration of the rare earth elements in a particle reaches 200 mg/ml. The
      particles of the liquid-crystalline dispersion of the (DNA-gadolinium) complex
      maintain the properties for a long time. The combination of the microscopic size
      of particles, high concentration of gadolinium in particles and their stability
      opens a way to practical application of this new biomaterial.

PMID- 16293301
TI  - Biodegradable honeycomb-patterned film composed of poly(lactic acid) and
      dioleoylphosphatidylethanolamine.
AB  - Honeycomb-patterned films have been reported to be useful for scaffolds of cell
      culture in tissue engineering. In the present study, we investigated a new
      compound, dioleoylphosphatidylethanolamine (DOPE), a naturally derived
      phospholipid having unsaturated fatty acid moieties, as a surfactant for
      fabricating honeycomb-patterned poly(d,l-lactide) (PLA) film. Only DOPE among
      commercially available phospholipids was useful as a surfactant, and it showed
      good solubility in PLA/chloroform solution and an excellent property for
      fabricating honeycomb-patterned film (the concentration of DOPE was from 0.2% to
      20% by weight based on the weight of PLA). The pore size of the honeycomb was
      uniform, and all pores were interconnected with each other. The contact angle of
      water on the honeycomb-patterned film was affected by the amount of DOPE. Time-of
      flight secondary ion mass spectrometer (TOF-SIMS) data suggested that DOPE was
      concentrated on the surface of the honeycomb-patterned film. To investigate cell
      proliferation and adhesion on the honeycomb-patterned film, NIH3T3 fibroblast
      cells were cultured on the film. The NIH3T3 cells adhered well on the honeycomb
      patterned PLA film with DOPE (PLA-DOPE) and showed good cell proliferation
      compared to that on honeycomb-patterned PLA film fabricated with a copolymer
      (CAP) of dodecylacrylamide and omega-carboxyhexylacrylamide (PLA-CAP). These
      results suggest that the honeycomb-patterned PLA-DOPE can be applicable as a
      scaffold for cells with better profiles in comparison with PLA-CAP.

PMID- 16293302
TI  - Responses of mesenchymal stem cell to chitosan-coralline composites
      microstructured using coralline as gas forming agent.
AB  - Macroporous composites made of coralline:chitosan with new microstructural
      features were studied for their scaffolding potential in in vitro bone
      regeneration. By using different ratios of natural coralline powder, as in situ
      gas forming agent and reinforcing phase, followed by freeze-drying, scaffolds
      with controlled porosity and pore structure were prepared and cultured with
      mesenchymal stem cells (MSCs). Their supportive activity of cellular attachment,
      proliferation and differentiation were assessed through cell morphology studies,
      DNA content, alkaline phosphatase (ALP) activity and osteocalcin (OC) release.
      The coralline scaffolds showed by far the highest evaluation of cell number and
      ALP activity over all the other chitosan-based scaffolds. They were the only
      material on which the OC protein was released throughout the study. When used as
      a component of the chitosan composite scaffolds, these coralline's favourable
      properties seemed to improve the overall performance of the chitosan. Distinct
      cell morphology and osteoblastic phenotype expression were observed depending on
      the coralline-to-chitosan ratios composing the scaffolds. The coralline-chitosan
      composite scaffolds containing high coralline ratios generally showed higher
      total cell number, ALP activity and OC protein expression comparing to chitosan
      scaffolds. The results of this study strongly suggest that coralline:chitosan
      composite, especially those having a high coralline content, may enhance
      adhesion, proliferation and osteogenic differentiation of MSCs in comparison with
      pure chitosan. Coralline:chitosan composites could therefore be used as
      attractive scaffolds for developing new strategies for in vitro tissue
      engineering.

PMID- 16293303
TI  - Histo-morphology of the uterus and early placenta of the African buffalo
      (Syncerus caffer) and comparative placentome morphology of the African buffalo
      and cattle (Bos taurus).
AB  - Differences exist in reproductive physiology between African buffalo (Syncerus
      caffer), cattle (Bos taurus) and water buffalo (Bubalus bubalis). The aim of this
      study was to histo-morphologically compare the anatomy of non-pregnant and
      pregnant uteri of buffalo and cattle. Two non-pregnant uteri and placentae of six
      pregnant African buffalo were used. Early placentome formation (fetal crown rump
      length (CRL): 2-17.5 cm) in S. caffer and B. taurus was compared. The endometrium
      of buffalo uteri comprises round to ovoid, dome-shaped and gland-free caruncles.
      A predominantly simple columnar epithelium of non-ciliated cells covers
      caruncular tissue, while, additionally, ciliated cells occur in the epithelium of
      the intercaruncular areas and within the simple columnar or pseudostratified
      epithelium of the endometrial glands. During early gestation, multiple
      placentomes develop. Unlike the placentomes in cattle at similar CRL, buffalo
      placentomes do not develop a caruncular stalk. The sessile, dome-shaped buffalo
      placentome has simple, slightly conical villi branching less than in cattle, thus
      indicating different and less complex feto-maternal interdigitation than seen in
      the latter. A synepitheliochorial interhaemal barrier can be expected in the
      buffalo placenta, as the occurrence and ultrastructure of trophoblast giant cells
      resemble those described in cattle.

PMID- 16293304
TI  - Reporting possible sexual abuse: a qualitative study on children's perspectives
      and the context for disclosure.
AB  - OBJECTIVE: The present study investigated the context in which children were able
      to report their child sexual abuse experiences and the children's views as to
      what made it difficult to talk about abuse and what helped them in the disclosing
      process. The aim was to study disclosures as they were occurring in their natural
      settings. METHOD: Data were obtained from therapeutic sessions and follow-up
      interviews from 20 families with 22 children. These children had said something
      that made their caregivers concerned about ongoing child sexual abuse.
      Qualitative analysis was conducted to capture the children's and caregiver's
      perspectives of the disclosure process. RESULTS: The children felt it was
      difficult to find situations containing enough privacy and prompts that they
      could share their experiences. They also were sensitive to others reactions, and
      whether their disclosures would be misinterpreted. When the children did disclose
      they did it in situations where the theme of child sexual abuse was in some form
      addressed or activated. The results indicate that disclosure is a fundamentally
      dialogical process that becomes less difficult if the children perceive that
      there is an opportunity to talk, and a purpose for speaking, and a connection has
      been established to what they are talking about. CONCLUSIONS: It is difficult for
      children to initiate a conversation about something secret, confusing and
      distressful, and where there are few conversational routines in a family for
      talking about such themes. Children also are sensitive to the needs of their
      caregivers and fear consequences for their family and offender. Children need a
      supportive structure or scaffold in order to reveal their experiences of child
      sexual abuse.

PMID- 16293305
TI  - Child and adolescent abuse and subsequent victimization: a prospective study.
AB  - OBJECTIVE: We investigated the possible reciprocal relationship between
      victimization experiences and psychological functioning by assessing abuse
      experiences in childhood, adolescence, and during a 2-month follow-up period.
      METHOD: At the beginning of the study (Time 1), abuse histories, trauma and
      depressive symptoms, and interpersonal functioning were assessed in 551 college
      women. Subsequent victimization experiences and psychological outcomes were
      assessed at the follow-up (Time 2). RESULTS: Path analyses indicated that verbal
      abuse by the mother and father were predictive of various psychological outcomes
      as measured at Time 1 and emerged as the only significant predictors of
      adolescent dating violence. Adolescent dating violence subsequently predicted the
      experience of dating violence during the 2-month follow-up period. Paternal
      physical abuse predicted adolescent sexual victimization which subsequently
      predicted all symptom measures at Time 1. Conversely, the experience of
      adolescent physical dating violence was not predictive of any of the symptom
      measures at Time 1. For those women who experienced dating violence during the
      follow-up, however, the severity of their abusive experiences was related to both
      depression and interpersonal problems assessed at Time 2. In comparison, for
      those women who experienced sexual victimization during the follow-up period, the
      severity of their abusive experiences was related to trauma symptoms.
      Interpersonal problems emerged as both an aftereffect of adolescent sexual
      victimization experience and a predictor of a subsequent sexual victimization
      experience during the follow-up. CONCLUSIONS: Given that emotional abuse emerged
      as a predictor of adolescent dating violence and psychological outcomes,
      researchers and clinicians need to continue to explore this problem. Further, it
      is important to assess how interpersonal problems contribute to the risk of
      subsequent sexual victimization and to try to break the cycle between adolescent
      abuse experiences and subsequent physical and sexual assaults.

PMID- 16293307
TI  - False allegations of abuse and neglect when parents separate.
AB  - OBJECTIVE: The 1998 Canadian Incidence Study of Reported Child Abuse and Neglect
      (CIS-98) is the first national study to document the rate of intentionally false
      allegations of abuse and neglect investigated by child welfare services in
      Canada. This paper provides a detailed summary of the characteristics associated
      with intentionally false reports of child abuse and neglect within the context of
      parental separation. METHOD: A multistage sampling design was used, first to
      select a representative sample of 51 child welfare service areas across Canada.
      Child maltreatment investigations conducted in the selected sites during the
      months of October-December 1998 were tracked, yielding a final sample of 7,672
      child maltreatment investigations reported to child welfare authorities because
      of suspected child abuse or neglect. RESULTS: Consistent with other national
      studies of reported child maltreatment, CIS-98 data indicate that more than one
      third of maltreatment investigations are unsubstantiated, but only 4% of all
      cases are considered to be intentionally fabricated. Within the subsample of
      cases wherein a custody or access dispute has occurred, the rate of intentionally
      false allegations is higher: 12%. Results of this analysis show that neglect is
      the most common form of intentionally fabricated maltreatment, while anonymous
      reporters and noncustodial parents (usually fathers) most frequently make
      intentionally false reports. Of the intentionally false allegations of
      maltreatment tracked by the CIS-98, custodial parents (usually mothers) and
      children were least likely to fabricate reports of abuse or neglect. CONCLUSIONS:
      While the CIS-98 documents that the rate of intentionally false allegations is
      relatively low, these results raise important clinical and legal issues, which
      require further consideration.

PMID- 16293306
TI  - The prevalence and correlates of abuse among children with autism served in
      comprehensive community-based mental health settings.
AB  - OBJECTIVE: To determine the demographic and psychosocial correlates of physical
      and sexual abuse among children with autism. METHODS: Data collected from 1997 to
      2000 through the national evaluation of the Comprehensive Community Mental Health
      Services for Children and their Families Program on 156 children with autism were
      used. Data included a baseline assessment of child and family psychosocial
      experiences and presenting problems associated with referral into system-of-care
      service, demographic information, and a clinical record review to obtain
      psychiatric diagnosis. Binary and multinomial logistic regression was used to
      determine the association of different characteristics of children who were
      abused compared with those who were not abused. RESULTS: Caregivers reported that
      18.5% of children with autism had been physically abused and 16.6% had been
      sexually abused. Physically abused children more likely had engaged in sexual
      acting out or abusive behavior, had made a suicide attempt, or had conduct
      related or academic problems. Sexually abused children more likely had engaged in
      sexual acting out or abusive behavior, suicidal or other self-injurious behavior,
      had run away from home, or had a psychiatric hospitalization. In adjusted
      multivariate models, the relationship between sexual abuse and sexual acting out,
      running away from home and suicidal attempts persisted. CONCLUSION: Based on the
      prevalence of abuse and its association with various behaviors, clinicians should
      be as attuned to the psychosocial histories of children with autism as they are
      for other children, and consider the potential of abuse when these behaviors are
      observed.

PMID- 16293308
TI  - False accusations of child maltreatment: a contested issue.

PMID- 16293310
TI  - Detection of Salmonella invA by isothermal and chimeric primer-initiated
      amplification of nucleic acids (ICAN) in Zambia.
AB  - The isothermal and chimeric primer-initiated amplification of nucleic acids
      (ICAN) is a new isothermal DNA amplification method composed of exo Bca DNA
      polymerase, RNaseH and DNA-RNA chimeric primers. We detected invA of Salmonella
      from chicken carcasses, egg yolk and cattle fecal samples. Fifty-three of 59
      isolates were invA-positive in ICAN-chromatostrip detection. The result was
      consistent with those obtained by standard PCR. Salmonella invA was detected in
      12 of 14 carcass rinses by ICAN, while in 7 of 14 rinses by standard PCR. These
      results indicate that ICAN is an efficient, sensitive and simple system to detect
      invA of Salmonella species in developing countries such as Zambia.

PMID- 16293312
TI  - Ce(4+) induced down-regulation of ERK-like MAPK and activation of nucleases
      during the apoptosis of cultured Taxus cuspidata cells.
AB  - Ce(4+) (Ce(NH(4))(2)(NO(3))(6)) at 1mM induces apoptosis of suspension cultures
      of Taxus cuspidata cells; however, the underlying signal mechanisms are unknown.
      We show here that a 46-kDa ERK (extracellular signal-regulated kinase)-like MAPK
      appears to be down-regulated at 4h, and remains at low levels for up to 48 h. An
      inhibitor of superoxide anions (O(2)(-)) generation, diphenyl iodonium (DPI)
      successfully blocks down-regulation of ERK-like MAPK and degradation of DNA.
      Moreover, a 41-kDa p38-like MAPK activity remains unchanged from 0.5 to 48 h. The
      p38 inhibitor SB202190 effectively inhibits p38-like MAPK activity, however,
      SB202190 fails to modify the apoptotic rate at concentrations up to 100 microM.
      Three nuclease (34-kDa, 22-kDa and 20-kDa) activities are profoundly enhanced in
      Ce(4+)-induced T. cuspidata cells. They have an optimum pH at 6.8, and are
      stimulated by Ca(2+)/Mg(2+). Caspase-3 inhibitor, Ac-DEVD-CHO, does not attenuate
      the 34-kDa nuclease activity, but inhibits the 22-kDa and the 20-kDa nuclease
      activities. In addition, inhibition of O(2)(-) generation by DPI significantly
      reduces the three nuclease activities. In conclusion, the present study suggests
      that down-regulation of ERK-like MAPK, burst of O(2)(-), activation of caspase-3
      like and induction of three nucleases as the key signaling events mediating
      apoptosis in Ce(4+)-induced cultured T. cuspidata cells.

PMID- 16293311
TI  - Induction of local protective immunity to Eimeria acervulina by a Lactobacillus
      based probiotic.
AB  - Previously we have shown that resistance to Eimeria acervulina (EA) infection in
      broiler chickens was enhanced by a probiotic treatment. In the present studies,
      we examined cytokine and oocyst production under similar conditions using a
      commercial Lactobacillus-based probiotic. Day-old male broiler chicks were fed
      control or probiotic diets and were orally challenged with either 2x10(4)
      (Experiment 1) or 1x10(4) (Experiment 2) oocysts of EA at 3 weeks of age. For the
      first experiment, fecal oocyst shedding and IFN-gamma levels in the culture
      supernatants of ConA-stimulated spleen lymphocytes were evaluated. Humoral and
      local cell-mediated immunity in the second experiment were assessed by evaluating
      antibody and cytokine (IFN-gamma and IL-2) levels in sera and intestinal
      secretions on a 3-day interval post inoculation. Results showed small but
      significant (P<0.05) differences in cytokine levels and oocyst production but not
      antibody levels between the probiotic-treated and control groups. Collectively,
      these data suggest a positive impact of the probiotic on cellular immune
      responses of infected broilers as compared to control chickens resulting in
      enhanced resistance to EA as shown in reduced fecal oocyst shedding. The results
      showed an immunoregulatory effect of probiotic diets on the local cell-mediated
      immunity in poultry and provide a rationale for further study to investigate the
      beneficial effects of Lactobacillus-based probiotics in food animals.

PMID- 16293313
TI  - In situ monitoring of polymerase extension rate and adaptive feedback control of
      PCR by using fluorescence measurements.
AB  - Real time PCR detection systems based on fluorescence detection from
      intercalating dyes (such as SYBR Green I) typically take only single point
      measurements during every cycle to quantify the amplification. In this process
      key information about enzymatic kinetics is lost. In this work we measure SYBR
      Green I fluorescence intensity every 0.5 s within a cycle during PCR in
      polypropylene tubes. We observe that the intensity during the extension cycle
      increases while the template is being extended. Results obtained for different
      lengths are used to estimate an in vitro polymerase activity rate of Thermus
      aquaticus and Thermus brockianus. An important practical consequence of this
      result is that the extension time of each PCR cycle can be individually optimized
      while the reaction is in progress. We demonstrate this idea of adaptive feedback
      control and show that the total number of cycles and total time required to reach
      maximum fluorescence is reduced as compared to conventional PCR.

PMID- 16293315
TI  - High throughput analysis of endogenous glutamate release using a fluorescence
      plate reader.
AB  - Recent discoveries of different modes of exocytosis and a plethora of molecules
      involved in neurotransmitter release has resulted in demand for more rapid and
      efficient methods for monitoring endogenous glutamate release from various tissue
      sources. In this article, we describe a high throughput microplate version of the
      enzyme-linked fluorescence detection method for the measurement of released
      glutamate, which utilises glutamate dehydrogenase, and the reduction of NADP to
      NADPH. Previous versions of this method rely upon cuvette-based fluorimeters for
      detection that are limited by large sample volumes and small numbers of samples
      that can be measured simultaneously. Comparison between the two methods shows
      that the microplate assay has comparable performance to the cuvette-based assay
      but has the capacity to analyse many times more samples in a given run. This
      increased capacity provides improved experimental design opportunities, higher
      experimental throughput and better comparison between experimental conditions.

PMID- 16293314
TI  - Fluctuations in Xenopus oocytes protein phosphorylation levels during two
      electrode voltage clamp measurements.
AB  - The biophysical and pharmacological properties of ion channels and transporters
      are often studied in exogenous expression systems using either the two-electrode
      voltage clamp (TEVC) in Xenopus oocytes or the patch clamp techniques. Cells
      machinery is trusted to produce active proteins that are correctly phosphorylated
      and glycosylated. However, native physiological cellular processes that might be
      altered during the course of the experiment are often ignored. Here, we detected
      and quantified the effects of various electrophysiological recording conditions
      on the phosphorylation levels of Xenopus oocytes proteins, including membrane
      proteins, as phosphorylation/dephosphorylation events modulate ion channels
      gating and cell surface expression. Two strategies were chosen to determine
      relative protein phosphorylation levels: a direct detection with a phospho
      Ser/Thr PKA substrate antibody, and a functional method employing two different
      leak potassium channels as indicators, chosen based on their opposite responses
      to protein kinase phosphorylation. We report that holding potential, and bath
      solution properties such as pH, osmolarity, temperature and ion composition,
      dramatically affect protein phosphorylation levels in Xenopus oocytes. Our
      results might explain some of the fluctuations in the biophysical properties of
      expressed channels, often observed during electrophysiological measurements.
      Minimizing possible misinterpretations could be achieved using either mutated,
      kinase insensitive, channels or kinases/phosphatases modulators.

PMID- 16293316
TI  - Desmoglein-1 is a minor autoantigen in dogs with pemphigus foliaceus.
AB  - The majority of human patients with pemphigus foliaceus (PF) have circulating IgG
      autoantibodies that target conformational epitopes on the desmosomal cadherin
      desmoglein-1 (dsg1). Limited studies using immunoblot techniques suggested that
      the principal autoantigen in dogs with PF might also be dsg1. It was the
      objective of this study to test this hypothesis. A comprehensive survey of canine
      PF sera was conducted using a novel screening strategy that detects
      conformational epitopes. This method consists of the ectopic expression of canine
      dsg1 at the surface of human 293T epithelial kidney cells and their live
      screening, i.e. prior to fixation. Out of seven control human PF sera that bound
      to canine epidermis, three (57%) contained IgG autoantibodies that recognized
      ectopically expressed canine dsg1 with a membrane and punctate pattern. Out of 83
      canine PF sera only five (6%) contained IgG that recognized canine dsg1.
      Consistent with findings for human PF sera obtained in this study, autoantibody
      binding was conformation- and glycosylation-dependent as demonstrated by calcium
      chelation with EDTA and tunicamycin or wheat germ agglutinin treatment,
      respectively. In conclusion, these studies establish canine dsg1 as a minor
      autoantigen for canine PF. Antigenic epitopes appear to be conformation- and
      glycosylation-dependent.

PMID- 16293317
TI  - Bacterial etiology of acute otitis media and clinical efficacy of amoxicillin
      clavulanate versus azithromycin.
AB  - BACKGROUND: Acute otitis media (AOM) is one of the most common acute bacterial
      infection in childhood and also the most frequent reason for outpatient
      antibiotic therapy. Little recent information about susceptibility patterns of
      AOM bacterial pathogens in Turkish children has been reported. OBJECTIVE: To
      determine the bacterial etiology of acute otitis media in children and to compare
      the efficiency of 3 days course of azithromycin with a 10 days course of
      amoxicillin-clavulanate. METHODS: This prospective, single blind, randomised
      comparative study was carried out in 180 children with AOM. Paracentesis was
      performed for middle ear fluid culture before the first dose antibiotic therapy.
      Children with acute otitis media were randomised to receive either low dose
      amoxicillin-clavulanate (45/6.4 mg/kg/day in two divided doses for 10 days) or
      low dose azithromycin (10mg/kg/day for 3 days). Clinical response was assessed on
      days 2-4, 11-13, 26-28. RESULTS: Bacterial pathogens were isolated from 108 (60%)
      of 180 children. Streptococcus pneumoniae was the most common isolated pathogen
      (39.7%), followed by Haemophilus influenzae (20.7%), Moraxella catarrhalis
      (15.5%), Staphylococcus aureus (13.8%), Group A beta-hemolytic streptococcus
      (5.1%), Escherichia coli (3.4%) and Enterococcus faecalis (1.7%). This study
      demonstrated low resistance rates compared to studies of different countries.
      Although clinical response rates were better in patients treated with amoxicillin
      clavulanate, this was not statistically significant [86.6% (78 of 90)] versus
      [95.2% (80 of 84)]. Success rates of amoxicillin-clavulanate were high for both
      S. pneumoniae and H. influenzae. Difference between success rates was not
      statistically significant (P=0.144 and 0.352). CONCLUSIONS: Bacteria were
      isolated in 60% of AOM cases. The clinical efficiency of amoxicillin-clavulanate
      was found to be equal compared to azithromycin in children with acute otitis
      media.

PMID- 16293318
TI  - Stenting for bilateral congenital choanal atresia--a new technique.
AB  - We describe a new nasal stent for the treatment of bilateral congenital choanal
      atresia. The stent is made up of reinforced endotracheal tube mounted on a portex
      carrier tube. It potentially causes less internal crusting and stent blockage and
      is secured without sutures. It remains patent for at least 4 weeks. We have used
      the stent successfully in six patients between 1998 and 2004 at Leeds General
      Infirmary and present the data collected retrospectively. The current practice in
      the UK for treatment and stenting for congenital choanal atresia was investigated
      by a prospective internet based questionnaire sent to 18 consultant paediatric
      otolaryngologists of whom 12 (67%) responded. Their experience and results are
      reported. The literature has been reviewed.

PMID- 16293320
TI  - Hemifacial spasm associated with otitis media with effusion: a first reported
      case.
AB  - Hemifacial spasm is a condition consisting of unilateral paroxysmal involuntary
      contractions of the muscles innervated by the facial nerve. The most common
      etiology is a vascular loop compression at the root exit zone of the nerve. We
      present here a first reported case of hemifacial spasm associated with otitis
      media with effusion, in a 6-year-old girl, which was relieved immediately
      following ventilation tubes insertion. A proposed mechanism is described.

PMID- 16293319
TI  - Pediatric paranasal sinus mucoceles: etiologic factors, management and outcome.
AB  - OBJECTIVES: To study the local and general etiological factors of paranasal sinus
      mucoceles in the pediatric population and to evaluate and discuss the clinical
      management and the results of endonasal marsupialization. DESIGN: Retrospective
      study. PATIENTS AND METHODS: A series of 10 cases of paranasal sinus mucocele in
      children were managed. For imaging, CT-scan and, sometimes MRI were performed. An
      ophthalmologic evaluation was performed preoperatively in all cases, and post
      operatively in case of preoperative trouble. All patients were treated with
      endoscopic surgical procedure. Authors also looked for etiological factors.
      RESULTS: Cystic fibrosis was found in 6 cases out of 10. Others etiological
      factors were trauma and inflammatory process; one case was strictly idiopathic.
      Three patients out of 10 had ophthalmologic trouble related with the mucocele.
      With a mean follow-up of 17 months, neither recurrence nor complication were
      noted. All patients with ophthalmologic complain were free of trouble after
      surgery. CONCLUSION: Paranasal sinus mucoceles in children are still rare. In our
      experience, 9 out of 10 patients had predisposing factors, especially cystic
      fibrosis. Imaging with CT-scan and MRI allow the physician to rule out other
      tumors such as meningoceles or rhabdomyosarcoma. Endoscopic endonasal surgery is
      nowadays the gold standard for the treatment of paranasal sinus mucoceles.

PMID- 16293321
TI  - Real-time RT-PCR and SYBR Green I melting curve analysis for the identification
      of Plum pox virus strains C, EA, and W: effect of amplicon size, melt rate, and
      dye translocation.
AB  - Real-time RT-PCR and SYBR green I melt curve analysis of a 74 bp amplicon enabled
      identification of Plum pox virus strains C, EA, and W, with distinct T(m)'s
      associated with each strain. This test is a useful supplement to a real-time RT
      PCR test described earlier that was used to distinguish PPV strains D and M. A
      longer fragment of 155 bp was not effective for strain identification. A
      simplified one-tube protocol, with dithiothreitol eliminated from the reaction,
      showed similar sensitivity when compared to a two-tube protocol. For melt curve
      analysis, a slower melt rate of 0.1 degrees C/s, compared to 0.4 degrees C/s, was
      effective for detecting weak amplicons, and improved resolution of the T(m) of
      amplicons amplified simultaneously. SYBR green I was useful for duplex melt curve
      analysis. In repeated melt run treatments (total of 14) of a single sample
      containing co-amplified targets, complete translocation of SYBR green I was
      observed, going from a 74 bp fragment to a 114 bp fragment. The duration of the
      melt run may be a critical factor affecting SYBR green I binding and
      translocation, and its manipulation may facilitate improved resolution and
      simultaneous detection of multiple targets. This phenomenon may explain
      inconsistent SYBR green I fluorescence patterns associated with melt curve
      analysis of some amplicon complexes.

PMID- 16293322
TI  - Spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley rats differ in
      performance on a win-shift task in the water radial arm maze.
AB  - The spontaneously hypertensive rat (SHR) is a commonly used animal model of
      attention deficit hyperactivity disorder. Previous literature is inconclusive
      with respect to the exact nature of memory impairments in this strain. The
      objective of this study was to assess spatial memory as measured by performance
      of male SHR, Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats on a win-shift
      version of the water radial arm maze. On this task, all strains made more errors
      on Trial 4 when the mnemonic demand was highest, and showed a similar response
      when the delay was increased from 60s to 2h on Week 3. Both SHR and WKY rats made
      more reference memory errors than SD, however, SHR showed minimal improvement
      over weeks. The increase in errors may be due to a greater inclination of SHR and
      WKY to use a chaining strategy of entering consecutive arms than SD. Furthermore,
      the number of incomplete arm entries into reference memory arms decreased over
      weeks in WKY and SD, but increased in SHR, suggesting increased impulsivity of
      SHR at the later stages of testing. Although based on number of errors, the data
      indicate that SHR may have memory deficits, the data relating to arm entries
      suggest that the minimal improvement in SHR over weeks may have been due to
      greater impulsivity in the later weeks, rather than defective memory. Thus, these
      findings are consistent with SHR having impairments with selection of appropriate
      behavioural responses in a goal-directed task.

PMID- 16293323
TI  - Proteomic analysis of the entomopathogenic nematode Steinernema feltiae IS-6 IJs
      under evaporative and osmotic stresses.
AB  - In order to improve the storage capability under desiccation of the widely sold
      biological insecticides based on entomopathogenic nematodes (EPNs), we need to
      understand how these organisms respond to desiccation stress. As part of our
      studies to achieve this, we studied survival and protein expression in infective
      juveniles of the EPN Steinernema feltiae IS-6 when exposed to evaporative
      (exposure to 97% relative humidity (RH) for 3 days, followed by a 1-day exposure
      to 85% RH) and osmotic (exposure to 24% glycerol for 8h) stresses. More than 400
      protein spots that were detected by proteomic analysis showed reproducible
      abundance within replications. Of these, 10 spots and 7 spots showed detectable
      changes in abundance under evaporative and osmotic stress, respectively, compared
      to fully hydrated nematodes. Three spots exhibited a differential response
      pattern between evaporative and osmotic desiccation (one was down regulated and
      two were novel in evaporative desiccation). Peptide mass mapping with MALDI-TOF
      mass spectrometry (MS) identified 10 desiccation-response proteins, among which
      several are known to be stress responsive including heat shock protein 60,
      coenzyme q biosynthesis protein, inositol monophosphatase and fumarate lyase that
      were found in both stresses. Other identified proteins are known to be involved
      in the cell cycle regulation, regulation of gene transcription, organization of
      macromolecular structure and some currently have no known functions. Our results
      suggest that it is unlikely that improvement of desiccation tolerance in EPNs can
      be achieved through genetic transformation and addition of single genes and that
      selective breeding could be the best approach to generate desiccation resistant
      worms.

PMID- 16293325
TI  - Elevated hydroperoxide levels as a prognostic predictor of mortality in a cohort
      of patients with cardiovascular disease.
AB  - The aim of this study was to evaluate whether hydroperoxide levels, an index of
      oxidative stress, predict cardiac and total death in patients with cardiovascular
      disease. Serum hydroperoxide levels were measured in 157 consecutive inpatients,
      followed during a mean follow-up of 20+/-0.3 months. Elevated oxidative stress
      resulted in an independent predictors for cardiac death, suggesting that
      hydroperoxide evaluation could provide an adjunctive estimate in the evaluation
      of prognosis in the cardiovascular clinical setting.

PMID- 16293324
TI  - Right-to-left shunting with normal pulmonary pressure complicating atrial septal
      defect surgery.
AB  - We report on a patient in whom a right-to-left shunt with normal pulmonary
      arterial pressures occurred after surgery of an inferior vena caval sinus venosus
      type atrial septal defect. In addition to the inferior vena cava to left atrium
      anatomic defect, the exceptional occurrence of a post-operative right atrial
      inflow stenosis contributed to the right-to-left shunting.

PMID- 16293326
TI  - Stunning and left ventricular function--how long is the ventricle knocked out?
      Left ventricular function correlated with ischemic burden and recovery time after
      stress.
AB  - PURPOSE: Little is known about the relation between severity of ischemia and
      duration of myocardial stunning. The aim of this study was therefore to
      characterize the impact of ischemia on myocardial stunning and on its duration.
      METHODS: 310 patients (pts) who underwent myocardial perfusion SPECT (MPS) were
      evaluated. MPS acquired with a rest Thallium/stress Technetium-99m sestamibi
      protocol were scored with respect to % myocardium ischemic. Left ventricular post
      stress ejection fraction (psEF) was evaluated by the widely used QGS algorithm.
      Resting LVEF (rEF) was assessed by invasive ventriculography. Patient groups were
      then compared with respect to different extents of ischemia and different time
      intervals between stress and imaging (< or = 60 min and > 60 min after stress).
      RESULTS: 21% of pts had a normal MPS, 8% had evidence of scar, 37% had evidence
      of ischemia, and 34% had evidence of scar plus ischemia. Pts with normal MPS had
      a significantly higher psEF than pts with ischemia, 61+/-8% and 56+/-8%,
      respectively (p=0.006), whereas rEF was not different. Overall, pts with < or =
      10% myocardium ischemic had significantly higher psEF than pts with > 10%
      myocardium ischemic, 53+/-11% and 49+/-9%, respectively (p=0.006), whereas rEF
      was not different. In pts with evidence of ischemia who underwent imaging < or =
      60 min after stress testing, pts with < or = 10% myocardium ischemic had higher
      psEF than pts with > 10% myocardium ischemic, 60+/-7% and 53+/-8%, respectively
      (p=0.037). In contrast, pts with evidence of ischemia who underwent imaging > 60
      min after stress testing had similar psEF irrespective of extent of ischemia
      (53%+/-8 in pts with < or = 10% ischemia and 54%+/-8 in pts with > 10% myocardium
      ischemic, p=0.12). CONCLUSIONS: Ischemia had a significant impact on psEF in
      patients who underwent imaging less than 1 h after stress. More than one hour
      after stress testing stunning seems to be less relevant in the interpretation of
      psEF.

PMID- 16293327
TI  - Stakeholder position paper: dairy producer.
AB  - Bacterial antimicrobial resistance is a problem common to both animal and public
      health. An important public policy issue is to develop and implement prudent use
      practices where antimicrobials are used. As policy develops, there are questions
      regarding the use of antimicrobials in animal agriculture and whether these uses
      constitute prudent use. A series of papers assessing the risk to the public
      health from agricultural use of antimicrobials have consistently concluded that
      risk estimation is hampered by the lack of data that describe the amount, types,
      and uses of antimicrobials in animal agriculture. The absence of information has
      spurred efforts to develop a framework to collect these data. However, the
      reasons and benefit of collecting these data should be carefully defined. The
      dairy industry, contrasted to other major animal commodities, is not focused on
      meat production but on milk production. Milk production is constrained by disease
      and antimicrobial treatment is a common management tool, but unlike many other
      animal agricultural systems where the value and safety of the product is measured
      in the future; the value of milk is zero when an antimicrobial is used in a
      lactating cow and milk must be discarded because of residues. While there are
      exceptions, e.g. non-lactating cow therapy, this difference results in
      antimicrobials being used sporadically and directed at therapy rather than
      prophylactic uses. In the dairy industry, antimicrobial use data and its
      consequences may exist in sufficient detail or could be estimated from existing
      datasets without the expense of additional surveys. Finally, the main food
      product milk is mainly pasteurized and all shipments of milk from the farm to the
      processing plant are tested for the presence of antimicrobials. This makes the
      likelihood of farm-origin antimicrobials or bacteria appearing in finished
      product very low. This suggests that the use and quantity of antimicrobials in
      the dairy system has little impact on public health. This does not imply that the
      dairy industry does not have a significant role in developing guidelines for
      appropriate and careful application of antimicrobials, but the effort and cost to
      collect additional data should be used to fund efforts that improve our
      diagnostic and managerial skills. These data would change the use of
      antimicrobials by decreasing the rates of disease and ultimately decreasing
      prophylactic, metaphylactic and therapeutic use of antimicrobial. These studies
      and outcome are as important to the dairy industry as to public health.

PMID- 16293328
TI  - Validation of a commercially available cELISA test for canine neosporosis against
      an indirect fluorescent antibody test (IFAT).
AB  - A commercially available competitive enzyme-linked immunosorbent assay (cELISA,
      VMRD) was validated for the detection of Neospora caninum antibodies in the serum
      of dogs, using as a reference test an indirect fluorescent antibody test (IFAT,
      Fuller). A partial verification approach was used. A total of 618 dogs were
      screened with cELISA and a subset of positive and negative sera (n=237) were then
      tested with IFAT. Naive relative sensitivity (SE(nv)) and naive relative
      specificity (SP(nv)) of cELISA were calculated and then corrected (SE(corr);
      SP(corr)) for studies with partial validation. Results showed a SE(nv) of 72% and
      a SP(nv) of 89.3%; corrected estimates showed a SE(corr) of 47% and a SP(corr) of
      96%. ROC analysis showed that the cutoff recommended by the manufacturer (30%)
      corresponded to the highest naive sensitivity (72%) combined with a good naive
      specificity (90%) of cELISA. Corrected estimates of SE and SP for partial
      verification method revealed that SE of the cELISA is lower and SP is higher than
      naive estimates. The results suggest to use this test for confirmation of a
      clinical suspicion of neosporosis, and to use some techniques for adjustment of
      misclassification in prevalence and risk-factor studies.

PMID- 16293329
TI  - Deliberations of an Advisory Committee regarding priorities, sources, and methods
      for collecting animal antimicrobial use data in the United States.
AB  - This paper describes the methodological options for food animal antimicrobial use
      data collection in the United States, including data priorities, methods, and
      limitations that were identified by a diverse group of expert stakeholders. Four
      major categories of antimicrobial use data were identified based on the source of
      information and its proximity to actual use: end-user data, prescription data,
      manufacturing data, and distribution data. Criteria were developed to aid in
      evaluating the overall utility of each methodological option, and an attempt was
      made to develop a qualitative, composite "overall usefulness" score for each
      option. Concensus was not reached on option scores, therefore, the experts
      individually rated six methodological options relative to the evaluation
      criteria, and provided comments and rationale for each response. The responses
      serve as a microcosm of the issues and stakeholder perspective: most relevant to
      animal antimicrobial use data collection in the United States.

PMID- 16293330
TI  - Variety of morphological and electrophysiological properties of area postrema
      neurons in adult rat brain slices.
AB  - Whole-cell recordings were performed to examine the morphological properties of
      electrophysiologically classified area postrema (AP) neurons in rat brain slices.
      Using electrophysiological criteria, AP neurons were subdivided into three
      groups: (1) cells displaying both the hyperpolarization-activated cation current
      (I(h)) and the fast transient outward current (fast I(to)); (2) cells displaying
      only the fast I(to); (3) cells displaying only the slow I(to). All AP neurons had
      a single axon that was distinctly thinner than the cells' dendrites. No
      systematic differences, across groups, in the orientation of dendrites or axons
      were identified. Mean values of cell size and capacitance of neurons from group 3
      were significantly larger than those of the other groups. Interestingly, a number
      of cells from groups 1 and 3 but not group 2 were found to extend their dendrites
      into the nucleus tractus solitarius (NTS), suggesting that AP neurons could
      receive vagal afferent inputs at their dendritic termini within the NTS. Although
      the AP has been implicated to contain uniformly shaped neurons, this study
      indicates the presence of significantly different subpopulations of AP neurons,
      which were characterized not only electrophysiologically but also
      morphologically.

PMID- 16293331
TI  - Influence of kinetic parameters of high pressure processing on bacterial
      inactivation in a buffer system.
AB  - High pressure processing is recently applied in the food industry to inactivate
      spoilage and pathogenic microorganisms. Bacterial cells exhibit various
      barosensibility, and the role of pressurization, depressurization and constant
      pressure stage remain unknown. We investigated the effect of high pressure
      processing on Salmonella typhimurium and Listeria monocytogenes cells at 400 and
      500 MPa respectively in buffer pH 7 at 20 degrees C. We applied various
      pressurization/depressurization kinetic rates (1, 5 and 10 MPa/s for
      pressurization and 250, 20 and 5 MPa/s for depressurization), and various pulse
      series or pressure holding times. Results show that high pressure pulses reduced
      linearly the number of bacterial cells according to the product of pressure and
      time: we defined this product as a Barometric Power (BP). Reduction of both
      microorganisms increased when holding time increased from 5 to 20 min, and better
      results were obtained when the rate of pressurization and depressurization were
      increased.

PMID- 16293333
TI  - Generic model control of the specific growth rate in recombinant Escherichia coli
      cultivations.
AB  - Generic model control is shown to be a powerful tool for keeping a microbial
      cultivation process close to its predetermined (optimized) control profile. This
      is demonstrated at the example of the green fluorescent protein expressed in
      genetically modified Escherichia coli host cells. It is shown that the process
      can be run very closely to a predefined complex profile of the specific cell
      growth rate mu(t). Controlling the experiments at many different growth
      conditions is a straightforward way of effectively collecting the data necessary
      for optimization of recombinant protein production systems. Although the process
      dynamics is rather complex, the model for the controller can be kept quite
      simple. The control technique, used here for specific growth rate control, is
      quite universal and can be applied for different biotechnological processes as
      well.

PMID- 16293332
TI  - Competition between polyphosphate and glycogen accumulating organisms in enhanced
      biological phosphorus removal systems with acetate and propionate as carbon
      sources.
AB  - Enhanced biological phosphorus removal (EBPR) is a widely used process for
      achieving phosphorus removal from wastewater. A potential reason for EBPR failure
      is the undesirable growth of glycogen accumulating organisms (GAOs), which can
      compete for carbon sources with the bacterial group responsible for phosphorus
      removal from wastewater: the polyphosphate accumulating organisms (PAOs). This
      study investigates the impact of carbon source on EBPR performance and the
      competition between PAOs and GAOs. Two sequencing batch reactors (SBRs) were
      operated during a 4-6 month period and fed with a media containing acetate or
      propionate, respectively, as the sole carbon source. It was found that the
      acetate fed SBR rarely achieved a high level of phosphorus removal, and that a
      large portion of the microbial community was comprised of "Candidatus
      Competibacter phosphatis", a known GAO. The propionate fed SBR, however, achieved
      stable phosphorus removal throughout the study, apart from one brief disturbance.
      The bacterial community of the propionate fed SBR was dominated by "Candidatus
      Accumulibacter phosphatis", a known PAO, and did not contain Competibacter. In a
      separate experiment, another SBR was seeded with a mixture of PAOs and a group of
      alphaproteobacterial GAOs, both enriched with propionate as the sole carbon
      source. Stable EBPR was achieved and the PAO population increased while the GAOs
      appeared to be out-competed. The results of this paper suggest that propionate
      may provide PAOs with a selective advantage over GAOs in the PAO-GAO competition,
      particularly through the minimisation of Competibacter. Propionate may be a more
      suitable substrate than acetate for enhancing phosphorus removal in EBPR systems.

PMID- 16293334
TI  - Generation and selection of targeted adenoviruses embodying optimized vector
      properties.
AB  - The utility of adenovirus serotype 5 (Ad5)-based vectors for gene therapy
      applications would be improved by cell-specific targeting. However, strategies to
      redirect Ad5 vectors to alternate cellular receptors via replacement of the
      capsid fiber protein have often resulted in structurally unstable vectors. In
      view of this, we hypothesized that the selection of modified adenoviruses during
      their rescue and propagation would be a straightforward approach that guarantees
      the generation of functional, targeted vectors. Based on our first generation
      fiber-fibritin molecule, several new chimeric fibers containing variable amounts
      of fibritin and the Ad5 fiber shaft were analyzed via a new scheme for Ad vector
      selection. Our selected chimera, composed of the entire Ad5 fiber shaft fused to
      the 12th coiled-coil segment of fibritin, is capable of efficient capsid
      incorporation and ligand display. Moreover, transduction by the resultant vector
      is independent of the expression of the native Ad5 receptor. The incorporation of
      the Fc-binding domain of Staphylococcus aureus protein A at the carboxy terminus
      of this chimeric fiber facilitates targeting of the vector to a variety of
      cellular receptors by means of coupling with monoclonal antibodies. In addition,
      we have concluded that Ad5 vectors incorporating individual targeting ligands
      require individual optimization of the fiber-fibritin chimera, which may be
      accomplished by selecting the optimal fiber-fibritin variant at the stage of
      rescue of the virus in cells of interest, as described herein.

PMID- 16293335
TI  - Phylogenetic analysis of the gag region encoding the matrix protein of small
      ruminant lentiviruses: comparative analysis and molecular epidemiological
      applications.
AB  - Little sequence information exists on the matrix-protein (MA) encoding region of
      small ruminant lentiviruses (SRLV). Fifty-two novel sequences were established
      and permitted a first phylogenetic analysis of this region of the SRLV genome.
      The variability of the MA encoding region is higher compared to the gag region
      encoding the capsid protein and surprisingly close to that reported for the env
      gene. In contrast to primate lentiviruses, the deduced amino acid sequences of
      the N- and C-terminal domains of MA are variable. This permitted to pinpoint a
      basic domain in the N-terminal domain that is conserved in all lentiviruses and
      likely to play an important functional role. Additionally, a seven amino acid
      insertion was detected in all MVV strains, which may be used to differentiate
      CAEV and MVV isolates. A molecular epidemiology analysis based on these sequences
      indicates that the Italian lentivirus strains are closely related to each other
      and to the CAEV-CO strain, a prototypic strain isolated three decades ago in the
      US. This suggests a common origin of the SRLV circulating in the monitored
      flocks, possibly related to the introduction of infected goats in a negative
      population. Finally, this study shows that the MA region is suitable for
      phylogenetic studies and may be applied to monitor SRLV eradication programs.

PMID- 16293336
TI  - [Plantar orthoses and gonarthrosis].

PMID- 16293337
TI  - Treating patients with HCV genotype 1 and low viraemia: more than meets the eye.

PMID- 16293338
TI  - Treatment of lamivudine-resistant hepatitis B in HIV-infected persons: is
      adefovir dipivoxil the answer?

PMID- 16293339
TI  - The landscape of community health insurance in India: an overview based on 10
      case studies.
AB  - The Indian health system is mainly funded by out-of-pocket payments. More than
      80% of health care expenditure is borne by individual households. Only about 3%
      of the population, mostly those in the formal sector, benefit from some form of
      health insurance. Several Indian Non-Governmental Organisations (NGOs) have
      initiated Community Health Insurance (CHI) schemes within their existing
      development programmes. This article describes the principal features of the
      design and functioning of a selection of 10 CHI schemes and presents a brief
      overview of the current landscape of CHI in India. The schemes explicitly target
      the poorest and most vulnerable households in Indian society-scheduled tribes,
      scheduled castes and poor women. Three CHI management models can be
      distinguished. The first model consists of local NGOs acting as both insurer and
      provider. In the second model, the NGO is the insurer but does not itself provide
      care, which is then purchased from a private provider. In the third model, the
      NGO neither does provide health care nor acts as an insurer: the NGO, on behalf
      of a community, links with an insurer and purchases health care from a provider.
      The benefit packages generally include both primary and secondary care and most
      of the providers are in the private sector. Most of the schemes require external
      resources for financial sustainability. There is currently little information on
      the impact of CHI schemes on the performance of local health systems and more
      research is warranted in that respect.

PMID- 16293340
TI  - Properties of Orange-Pupa-Inducing Factor (OPIF) in the swallowtail butterfly,
      Papilio xuthus L.
AB  - Diapause pupae of the swallowtail butterfly Papilio xuthus L. exhibit diapause
      green, orange and brownish-orange color polymorphism. Development of orange pupae
      involves a neuroendocrine factor inducing orange pupa (Orange-Pupa-Inducing
      Factor, OPIF), which is secreted from the head-thoracic region during late
      pharate pupal stages, in particular from the ganglia of short-day animals located
      posteriorly from the second thoracic ganglion2 (TG2). This report describes
      certain properties of OPIF using bioassays involving ligated abdomens of short
      day pharate pupae. Localization of OPIF in the central nervous system of short
      day larvae indicated that it was present predominantly in TG2, thoracic ganglion3
      (TG3) and abdominal ganglion1 (AG1) complexes. OPIF activity in TG(2,3)-AG1
      complexes was over two times higher than in the more posteriorely located
      ganglia. The developmental profile of OPIF in last instar short-day larvae
      revealed that OPIF activity in larval ganglia posterior to TG2 became gradually
      higher as larval growth proceeded, suggesting that OPIF might be accumulated in
      TG(2,3)-AG(1-7) complexes as larvae prepare for pupal molting. Furthermore,
      ligated abdomens of short-day larvae developed into pupae of an orange type when
      a 2% NaCl extract containing OPIF prepared from TG(2,3)-AG(1-7) complexes of long
      day larvae was injected into ligated abdomens of short-day pharate pupae,
      indicating that OPIF is also present in long-day larvae. Additionally, a
      biochemical investigation using gel filtration chromatography showed that the
      molecular weight of OPIF was about 10 kDa.

PMID- 16293341
TI  - Effect of MELANOTAN, [Nle(4), D-Phe(7)]-alpha-MSH, on melanin synthesis in humans
      with MC1R variant alleles.
AB  - MELANOTAN (NDP-MSH) binds the MC1 receptor to significantly increase the
      eumelanin content of human skin cells. In this study of 77 Caucasian individuals,
      we investigated the effects of MELANOTAN in individuals with variant MC1R
      genotypes, as it has been suggested through in vitro studies that variant alleles
      decrease MELANOTAN binding efficacy, which would subsequently affect the
      synthesis of melanin. Administration of MELANOTAN produced a significant
      (p<0.001) increase in melanin density in treated, compared to placebo,
      individuals. Importantly, MELANOTAN increased the melanin density to a greater
      extent in individuals carrying the variant alleles Val60Leu, Asp84Glu, Val92Met,
      Arg142His, Arg151Cys, and Arg160Trp than in individuals with no variant alleles.
      This study demonstrates that MELANOTAN effectively increases the melanin content
      of skin in those individuals with MC1R variant alleles and therefore, those most
      in need of photoprotection.

PMID- 16293342
TI  - Role of endothelin (ETA) receptors in neonatal morphine withdrawal.
AB  - We have previously demonstrated role of central endothelin (ET) receptors in
      neonatal morphine tolerance. The present study was conducted to investigate
      involvement of central ET receptors in neonatal rat morphine withdrawal. The aim
      was to determine activation of G-proteins coupled to opioid and ET receptors by
      morphine and ET ligands in neonatal rat brains during morphine withdrawal.
      Pregnant female rats were rendered tolerant to morphine by chronic exposure to
      morphine pellets over 7 days. Withdrawal was induced on day 8 by removal of
      pellets. Rat pups were delivered by cesarean section 24 h after pellet removal. G
      protein stimulation induced by morphine; ET-1; ETA receptor antagonist,
      BMS182874; and ETB receptor agonist, IRL1620, was determined in the brain of
      neonatal rats undergoing morphine withdrawal by [35S]GTPgammaS binding assay.
      Morphine-induced maximal stimulation of G-protein in morphine withdrawal group
      (83.60%) was significantly higher compared to placebo control group (66.81%).
      EC50 value for ET-1-induced G-protein stimulation during morphine withdrawal
      (170.60 nM) was higher than control (62.5 nM). BMS182874, did not stimulate GTP
      binding in control but significantly increased maximal stimulation of G-proteins
      in morphine withdrawal (86.07%, EC50 = 31.25 nM). IRL1620-induced stimulation of
      G-proteins was similar in control and morphine withdrawal. The present findings
      indicate involvement of central ETA receptors in neonatal morphine withdrawal.

PMID- 16293343
TI  - Effects of leptin on memory processing.
AB  - Leptin is a peptide hormone secreted by adipose tissue. Studies have shown that
      leptin crosses the blood-brain barrier (BBB) by a saturable transport system
      where it acts within the hypothalamus to regulate food intake and energy
      expenditure. Leptin also acts in the hippocampus where it facilitates the
      induction of long-term potentiation and enhances NMDA receptor-mediated
      transmission. This suggests that leptin plays a role in learning and memory.
      Obese mice and rats, which have leptin receptor deficiency, have impaired spatial
      learning. In disease states such as diabetes, humans and animals develop leptin
      resistance at the BBB. This suggests that low leptin levels in the brain may be
      involved in cognitive deficits associated with diabetes. In the current study,
      the effects of leptin on post-training memory processing in CD-1 mice were
      examined. Mice were trained in T-maze footshock avoidance and step down
      inhibitory avoidance. Immediately after training, mice received bilateral
      injections of leptin into the hippocampus. Retention was tested 1 week later in
      the T-maze and 1 day later in step down inhibitory avoidance. Leptin
      administration improved retention of T-maze footshock avoidance and step down
      inhibitory avoidance. Leptin administered 24 h after T-maze training did not
      improve retention when tested 1 week after training. SAMP8 mice at 12 months of
      age have elevated amyloid-beta protein and impaired learning and memory. We
      examined the effect of leptin on memory processing in the hippocampus of 4 and 12
      months old SAMP8 mice. Leptin improved retention in both 4 and 12 months old
      SAMP8 mice; 12 month SAMP8 mice required a lower dose to improve memory compared
      to 4 months SAMP8 mice. The current results indicate that leptin in the
      hippocampus is involved in memory processing and suggests that low levels of
      leptin may be involved in cognitive deficits seen in disease states where leptin
      transport into the CNS is compromised.

PMID- 16293344
TI  - The cardiovascular responses to mu opioid agonist and antagonist in conscious
      normal and obese rats.
AB  - Beta-endorphin decreases blood pressure in normal rats but increases blood
      pressure in obese rats. Since beta-endorphins can bind both mu opioid and kappa
      opioid receptors we investigated the effect of a mu specific receptor agonist, D
      Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and a mu specific antagonist, D-Phe
      Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) on cardiovascular responses in conscious
      control and obese rats. Rats were also implanted with telemetry transmitters and
      intracerebroventricular (ICV) cannulas for recording and peptide administration.
      The mu agonist, DAMGO, increased blood pressure (BP) in control rats. DAMGO also
      increased BP in obese rats but only at high concentrations. The heart rate
      responses paralleled the MAP responses. CTAP, the mu antagonist, paradoxically
      increased the MAP in both control and obese rats. The responsiveness to the mu
      agonist and antagonist was greater in controls. In other animals the brains were
      excised and the ventral medial hypothalamic area removed and mu receptor
      expression determined using PCR. The expression of mu opioid receptors was
      increased in obese rats. We conclude that the mu opioids can stimulate
      cardiovascular responses, but the excitatory responsiveness was not increased in
      conscious obese rats.

PMID- 16293345
TI  - Melanocortin receptor signaling in RAW264.7 macrophage cell line.
AB  - Melanocortin peptides modulate cytokine release and adhesion molecule expression.
      Here we have investigated the early cell-signaling pathway responsible for the
      induction of interleukin-10 (IL-10) in RAW264.7 cells. Cell incubation with
      ACTH(1-39) or MTII (melanotan II) did not alter ERK1/2 and JNK phosphorylation,
      while p38 phosphorylation and intracellular cAMP accumulation occurred within
      minutes. ACTH(1-39) and MTII provoked a time-dependent accumulation of IL-10 that
      was abrogated by the PKA inhibitor H-89 and only partially blocked by the p38
      MAPK inhibitor SB203580. Thus, in RAW264.7 cells, IL-10 induction by the
      melanocortins is via the PKA pathway, and this mechanism could contribute to
      their anti-inflammatory profile.

PMID- 16293346
TI  - Apoptosis inhibition in ischemic brain by intraperitoneal PTD-BIR3-RING (XIAP).
AB  - Anti-apoptotic treatment is a promising strategy for neuroprotection against
      various brain injuries resulting from ischemia or neuron degeneration. X-linked
      inhibitor of apoptosis protein (XIAP) is regarded as the most effective apoptosis
      inhibitor, in which C-terminal structure BIR3-RING mainly inhibits caspase-9
      dependent apoptosis. In the present study, we fused XIAP (BIR3-RING) to the
      protein transduction domain (PTD) of antennapedia homeodomain of Drosophila (Antp
      HD), and then used the oxygen glucose deprivation (OGD)-induced hippocampal
      slices injury in vitro, and the rat transient middle cerebral artery ischemia
      (tMCAO) models in vivo, to explore the anti-apoptotic effect of this recombinant
      protein. The results showed that the PTD could efficiently mediate the
      transduction of BIR3-RING into the hippocampal slices and rat brains. PTD-BIR3
      RING could decrease OGD-induced cell death in brain slices (p < 0.05).
      Intraperitoneal injection of PTD-BIR3-RING could attenuate terminal
      deoynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) positive
      cells and decrease cleaved caspase-3 in the ischemic bounder zone compared with
      the control animals (p < 0.05). Further studies showed that ischemia-induced
      neurological outcomes were improved in rats with PTD-BIR3-RING treatment (p <
      0.05). These results demonstrate that PTD-BIR3-RING could attenuate cell death in
      OGD hippocampal slices and decrease cell apoptosis in tMCAO brains through
      inhibiting of caspase-3 cleavage, suggesting that PTD-mediated protein
      transduction provides a novel and effective approach for the therapies of brain
      diseases such as cerebral ischemia.

PMID- 16293347
TI  - Rapid modulation of TRH and TRH-like peptide levels in rat brain and peripheral
      tissues by corticosterone.
AB  - Disturbance of glucocorticoid signaling has been implicated in several
      neuropsychiatric disorders including unipolar and bipolar depression and anxiety
      induced by maternal deprivation. Antidepressants have been shown to be
      neuroprotective and able to reverse damage to glia and neurons. Thyrotropin
      releasing hormone (TRH) is an endogenous antidepressant that reduces the
      expression of glycogen synthase kinase-3beta (GSK-3beta), an enzyme that
      hyperphosphorylates tau and is implicated in bipolar depression, diabetes and
      Alzheimer's disease. In order to understand the potential role of TRH and TRH
      like peptides both as mediators of the depressogenic effects of glucocorticoids
      and as potential therapeutics for neuropsychiatric disease, 300 g male Sprague
      Dawley rats were injected i.p. with 4 mg corticosterone/0.5 ml 50% DMSO+50%
      ethanol and sacrificed 0, 2, 4 and 8h later. Levels of TRH and TRH-like peptides
      were measured in various brain regions involved in mood regulation and pancreas
      and reproductive tissues that mediate the metabolic and reproductive impairments
      associated with high glucocorticoid levels. Significant increases, ranging from 2
      to 12-fold, in TRH or TRH-like peptide levels were observed in almost all brain
      regions studied at 4h after corticosterone injection. In cerebellum, TRH and TRH
      like peptides increased 4-14-fold by 8h. TRH-like peptide levels fell 86-98% at
      4h after treatment in testis. TRH, derived only from Leydig cells, was not
      affected. TRH and TRH-like peptides increased 2-4-fold at 8h in pancreas. TRH and
      TRH-like peptide concentrations in prostate were not affected by corticosterone
      up to 8h after injection. The 4h needed to detect a highly significant change in
      the TRH and TRH-like peptide levels in brain and peripheral tissues is consistent
      with the mediation of most corticosterone-effects via alterations in gene
      transcription.

PMID- 16293348
TI  - Structure of daunomycin complexed to d-TGATCA by two-dimensional nuclear magnetic
      resonance spectroscopy.
AB  - The anthracycline antibiotic daunomycin, having four fused rings and an amino
      sugar, is being used in the treatment of acute leukemia. Binding to DNA is
      generally believed to be essential for its activity. We have studied the
      interaction of daunomycin with DNA hexamer sequence d-(TGATCA)2 by titrating up
      to two drug molecules per duplex using nuclear magnetic resonance spectroscopy.
      The solution structure of 2:1 drug to DNA complex based on two dimensional
      nuclear Overhauser enhancement (NOE) spectroscopy and molecular dynamics
      calculations has been studied. The change in conformation of drug molecule on
      binding to DNA, deoxyribose conformation and glycosidic bond rotation has been
      obtained. The absence of sequential NOE connectivities at d-T1pG2 and d-C5pA6
      sites shows that the drug chromophore intercalates between these two base pairs.
      This is substantiated by intermolecular NOEs observed between nucleotide base
      protons and aromatic ring protons of drug molecule. A set of 17 intermolecular
      NOE interactions allowed the structure to be derived by restrained molecular
      dynamics simulations, which have been compared with that obtained by X-ray
      analysis. Several specific interactions between the drug and DNA protons are
      found to stabilize the formation of drug-DNA complex.

PMID- 16293349
TI  - Synthesis, antibacterial and antifungal activity of some new pyridazinone metal
      complexes.
AB  - The new various metal complexes of 5-benzoyl-4-hydroxy-2-methyl-6-phenyl-2H
      pyridazin-3-one were synthesized. All the complexes were evaluated for their
      antimicrobial activities against Gram-positive, Gram-negative bacteria and fungi
      using microdilution procedure. The Cd(II) and Ni(II) complexes exhibited
      selective and effective activities against one Gram-positive bacterium
      (Staphylococcus aureus ATCC 6538), one Gram-negative bacterium (Pseudomonas
      putida ATCC 12633) and against two yeast (Candida albicans ATCC 27541 and Candida
      tropicalis 1828) in contrast to poor activity observed other microorganisms. The
      new synthesized complexes were characterized using IR, 1H-NMR and UV spectral
      data together with elemental analysis.

PMID- 16293350
TI  - Optimization of a pharmacophore model for 5-HT4 agonists using CoMFA and receptor
      based alignment.
AB  - Twenty two 5-HT4 agonists obtained from our laboratory and the recent literature
      were used to develop a CoMFA model to predict 5-HT4 agonist activity. Two models
      were produced and compared for predictivity, the first by alignments based on
      atom overlapping (model A) and the second by adding agonist binding site
      interacting points of the 5-HT4 receptor (model B). Comparison of the two models
      showed that the q2 value for model A was 0.564 vs. 0.582 for model B. Model B
      indicated that the predictive power model stems from far lower steric
      contributions, 0.270 compared to model A's 0.502. The dominant defining features
      were the electrostatic contributions for model B, 0.664 up from 0.477 in model A.
      The contributions from the LogP factor were minimal, 0.085 in both models. The
      synthesized compounds showed agonist activity at mumol level.

PMID- 16293352
TI  - Short-term ingestion of Ginkgo biloba extract does not alter whole body insulin
      sensitivity in non-diabetic, pre-diabetic or type 2 diabetic subjects--a
      randomized double-blind placebo-controlled crossover study.
AB  - BACKGROUND & AIMS: Ingestion of Ginkgo biloba Extract (EGb 761) may increase
      pancreatic beta-cell function in both healthy subjects with normal glucose
      tolerance (NGT) as well as patients with Type 2 Diabetes mellitus (T2DM). Since
      hyperinsulinemia is a hallmark of T2DM, it is important to verify that increased
      insulin production is not due to increased insulin resistance. METHOD: NGT
      subjects (n = 10; age, 44.2 +/- 13.9 years old), impaired glucose tolerance (IGT)
      (n = 8; age 51.3 +/- 6.6 years old) and T2DM subjects (n = 8, 51.6 +/- 15.2 years
      old) completed a randomized, double-blind, placebo-controlled crossover study.
      After ingesting either EGb 761 (120 mg/day as a single dose) or placebo during
      each 3-month arm, a 2-step euglycemic insulin clamp was performed. RESULTS: At
      the low insulin infusion rate (10 mU/m2/min) the glucose metabolic rates (M
      values) were 3.5 +/- 1.5 vs. 3.0 +/- 0.5 mg/kg (P = 0.16), 3.0 +/- 0.4 vs. 2.8 +/
      0.8 mg/kg (P = 0.19) and 2.6 +/- 0.7 vs. 2.4 +/- 0.5 mg/kg (P = 0.09) for the
      placebo and EGb 761 cycles, in the NGT, IGT and T2DM subjects, respectively. At
      the high insulin infusion rate (40 mU/m2/min) the M values were 7.3+/-2.3 vs. 8.1
      +/- 2.5mg/kg (P = 0.07), 6.2 +/- 1.6 vs. 6.5 +/- 2.1 mg/kg (P = 0.32) and 3.6 +/-
      1.6 vs. 3.5 +/- 1.0 mg/kg (P = 0.34) for placebo vs. EGb 761 cycles, in the NGT,
      IGT and T2DM subjects, respectively. CONCLUSION: The ingestion of 120 mg of EGb
      761 as a single for 3 months did not produce insulin resistance in the non
      diabetic or pre-diabetic subjects or exacerbate the disease in the T2DM subjects.

PMID- 16293353
TI  - Allium sativum: nutritional properties.

PMID- 16293351
TI  - Trends in the nature of provision in ophthalmology services and resources and
      barriers to education in ophthalmic nursing: 3rd National UK survey.
AB  - Over the last decade in the United Kingdom (UK), the roles of nurses have become
      increasingly specialised to support a more efficient and effective health
      service. In ophthalmology, the changes are most visible in the growing number of
      patients being treated as day case and the greater nursing contribution to
      patient outcomes. To support this change there is a continuing need for
      educational institutions to create opportunities to meet the training needs of
      nurses working in both specialised areas and at the advance level of practice.
      This article reports on a 3rd national survey the aims of which were to
      investigate trends in the nature and provision of ophthalmic services and the
      resources and barriers to education in ophthalmic nursing. The results
      demonstrate that over the three surveys there has been a significant increase of
      pre-operative assessment units and a significant decrease of designated
      ophthalmic wards. Between the second and third survey, the results indicate fewer
      difficulties with funding but there has been an increase of respondents stating a
      lack of training institutions offering ophthalmic courses. The survey shows that
      at a time when nurses need to acquire ophthalmic nursing skills and knowledge
      there appear to be fewer opportunities for them to access ophthalmic courses.

PMID- 16293354
TI  - Air gun pellet injuries of the hand.
AB  - The purpose of this paper is to report our experience in a group of patients who
      suffered injuries by air gun pellets to the hand. There were 22 males and 2
      females, with a mean age of 12 years. The pellet was embedded in the hand in 18
      patients and it went through and through in the remaining six. There were no
      vascular injuries. Associated injuries to tendon, nerve or bone occurred in six
      patients. There was little soft-tissue devitalization and none of the fractures
      required fixation or splinting. Immediate postoperative mobilization resulted in
      full range of motion in all patients. In conclusion, pellets produce a different
      injury pattern, with a more benign course, than other types of bullet injury.

PMID- 16293355
TI  - Dorsal fracture dislocations of the proximal interphalangeal joint treated by
      open reduction and interfragmentary screw fixation: indications, approaches and
      results.
AB  - Many operative and non-operative treatments of dorsal fracture dislocations of
      the proximal interphalageal (PIP) joint have been described. Return of good joint
      function requires anatomical reduction of the articular fragments and restoration
      of joint congruity and a stable functional arc of motion, with the fixation
      construct stable enough for early mobilization. To prevent recurrent dorsal
      subluxation, the attachments of the ligamentous palmar restraints and the bony
      buttress provided by the palmar lip of the middle phalanx base must be restored.
      Open reduction and internal interfragmentary screw fixation using 1.5 or 1.3mm
      screws was employed in 12 fingers in 10 patients with unstable dorsal fracture
      dislocations of the PIP joints of Schenck grades III and IV. At an average follow
      up of 8.7 months, all patients in this series achieved good to excellent results
      and an average total active interphalangeal motion of 132 degrees (range 105
      degrees -165 degrees). Additional benefits over non-operative techniques included
      improved patient comfort and simplified nursing care and therapy supervision.

PMID- 16293356
TI  - Results of tri-ligament tenodesis: a modified Brunelli procedure in the
      management of scapholunate instability.
AB  - One hundred and sixty-two patients with a diagnosis of scapholunate instability
      underwent a modified Brunelli procedure over a 7-year period. One hundred and
      seventeen were assessed with the help of a questionnaire and, of these, 55
      patients attended for clinical evaluation. The mean follow-up was 4 (1-8) years.
      There were 72 patients with dynamic scapholunate instability and 45 patients with
      static instability. The average age was 38 years. There were 50 males and 67
      females. A total of 77 (62%) patients had no to mild pain with a mean visual
      analogue score of 3.67 (SD=2.5). The loss in the arc of flexion-extension was due
      to a reduced range of flexion (mean loss 31%), while 80% of extension was
      maintained, compared with the contralateral side. The grip strength on the
      operated side was reduced by 20% of the non-operated side. There was no
      statistically significant difference (P>0.05) in the range of movement or the
      grip strength between the static and dynamic group and patients with or without
      legal claims. Ninety (79%) patients were satisfied with the result of the surgery
      (good to excellent) and 88% of the patients felt that they would have the same
      surgery again. We feel that these results compare favourably with the early
      results published from this unit and recommend this procedure for dynamic and
      static scapholunate instability.

PMID- 16293357
TI  - External fixation of closed metacarpal and phalangeal fractures of digits. A
      prospective study of one hundred consecutive patients.
AB  - Stable and undisplaced phalangeal and metacarpal fractures treated with strapping
      or functional splinting and controlled active exercises offer from about 70 to
      80% of good results. The goal of treatment of closed unstable and displaced
      fractures should be to achieve similar or better outcome. External fixation
      combines the simplicity of time-honoured fixation with K-wires and an external
      frame to increase rigidity. This combination was used in a prospective study of
      100 consecutive patients with closed fractures of the proximal and middle
      phalanges and the distal three-quarters of the metacarpal bones. Good clinical
      results (TAM > or = 230 degrees) were obtained in 76% of isolated phalangeal
      fractures, in all metacarpal fractures and in 89% of multiple fractures.

PMID- 16293359
TI  - Rightward biases in free-viewing visual bisection tasks: implications for
      leftward responses biases on similar tasks.
AB  - Neurologically normal individuals exhibit strong leftward response biases during
      free-viewing perceptual judgments of brightness, quantity, and size. When
      participants view two mirror-reversed objects and they are forced to choose which
      object appears darker, more numerous, or larger, the stimulus with the relevant
      feature on the left side is chosen 60-75% of the time. This effect could be
      influenced by inaccurate judgments of the true centre-point of the objects being
      compared. In order to test this possibility, 10 participants completed three
      visual bisection tasks on stimuli known to elicit strong leftward response
      biases. Participants were monitored using a remote eye-tracking device and
      instructed to stare at the subjective midpoint of objects presented on a computer
      screen. Although it was predicted that bisection errors would deviate to the left
      of centre (as is the case in the line bisection literature), the opposite effect
      was found. Significant rightward bisection errors were evident on two of the
      three tasks, and the leftward biases seen during forced-choice tasks could be the
      result of misjudgments to the right of centre on these same tasks.

PMID- 16293358
TI  - Dorsal plating of unstable distal radius fractures using a bio-absorbable plating
      system and bone substitute.
AB  - This study reports the results of open reduction and internal fixation of 26
      unstable, intraarticular, dorsally displaced fractures of the distal radius using
      a bio-absorbable dorsal distal radius (Reunite) plate and calcium phosphate
      (Biobon) bone substitute. The bio-absorbable plate has the advantage of being low
      profile, easily contourable and angularly stable. In the majority of cases, this
      plate produces functional results comparable with metal plates. The Gartland and
      Werley score was excellent or good in 21 patients. The theoretical advantage over
      metal plates is in eliminating the need to remove the plate and hence the need
      for a second operation if implant-related extensor tenosynovitis occurs.
      Inflammatory tissue reaction to the degradation products of the plate is a
      potential concern, although the co-polymer ratio used in this plate appears to
      have reduced the severity of this reaction, which was seen in two patients in
      this series. The reduction was lost in five patients with severe dorsal
      comminution. Following this experience, we do not recommend this plating system
      for fractures with a metaphyseal gap of greater than 7 mm following reduction.

PMID- 16293360
TI  - Event-related potentials in adolescents with combined ADHD and CD disorder: a
      single stimulus paradigm.
AB  - Some studies of the event-related potentials demonstrated a reduction of the
      voluntary component P3 (P300 or P3b) in youngsters with the attention
      deficit/hyperactivity disorder (ADHD) or in conduct disorders (CD), and a
      reduction of the automatic processing component, mismatch negativity, in patients
      with both ADHD and CD (ADHD+CD). Recently, a passive auditory P3 potential has
      been elicited by a single stimulus. We therefore tried this potential study in 20
      healthy subjects and 20 teenagers with ADHD+CD to search for further evidence of
      the altered automatic cerebral processing in the latter. Subjects also answered a
      self-report Dimensional Assessment of Personality Pathology (DAPP). The patient
      group scored significantly higher on most DAPP traits that reflect problems of
      emotion control, showed significantly prolonged P2, N2, and P3, and reduced P3.
      In all subjects Stimulus Seeking was positively correlated with P3 latencies at
      Fz, Cz, and Pz, and with P3 amplitude at Cz. This study suggests that youngsters
      with ADHD+CD had pronounced emotion dysregulation, and prominent deficit in
      passive attention, as reflected by the automatic processing of auditory stimuli.

PMID- 16293361
TI  - Priming effects for affective vs. neutral faces.
AB  - Affective and Neutral Tasks (faces with negative or neutral content, with
      different lighting and orientation) requiring reaction time judgments of poser
      identity were administered to 32 participants. Speed and accuracy were better for
      the Affective than Neutral Task, consistent with literature suggesting
      facilitation of performance by affective content. Priming effects were
      significant for the Affective but not Neutral Task. An Explicit Post-Test
      indicated no conscious knowledge of the stimulus frequency that was associated
      with performance facilitation. Faster performance by female vs. male
      participants, and differential speeds and susceptibility to priming of different
      emotions were also found. Anger and shock were responded to most rapidly and
      accurately in several conditions, showed no gender differences, and showed
      significant priming for both RT and accuracy. Fear and pain were responded to
      least accurately, were associated with faster female than male reaction time, and
      the accuracy data showed a kind of reverse priming.

PMID- 16293362
TI  - Selected polychlorobiphenyls congeners bind to estrogen receptor alpha in human
      umbilical vascular endothelial (HUVE) cells modulating angiogenesis.
AB  - Endocrine disrupting chemicals (EDCs) can behave as agonists or antagonists of
      several hormone receptors, thus mimicking or antagonizing the physiological
      activity of endogenous ligands. The involvement of estrogens in the regulation of
      angiogenesis has convincingly been demonstrated by a large body of experimental
      studies. Some polychlorobiphenyls (PCBs), considered EDCs, interact with estrogen
      receptors (ERs), so it is possible that these exogenous compounds affect the
      angiogenic process. Using fluorescence polarization, we firstly assayed whether
      PCB 77 (3,3',4,4'-tetrachlorobiphenyl), PCB 153 (2,2',4,4',5,5'
      hexachlorobiphenyl) and PCB 156 (2,3,3',4,4',5-hexachlorobiphenyl) were able to
      bind to the alpha isoform of ER, recently found to be involved in angiogenesis.
      To discriminate the putative agonist or antagonist binding behaviour of these
      compounds, we tested their ability to activate, similarly to the natural ligand
      17-beta-estradiol (17betaE(2)), the extracellular-signal-regulated kinase (Erk)
      1/2 in human umbilical vascular endothelial (HUVE) cells. Finally, by using a new
      angiogenic assay, we evaluated the effect of PCBs treatment on microvessels
      neoformation. The data obtained in the present study showed that all the PCBs
      tested were able to bind to ERalpha and to elicit a response which can be
      agonistic or antagonistic; moreover, PCB 153 and PCB 77 can either positively or
      negatively modulate the angiogenic process, thus behaving as EDCs in endothelial
      cells.

PMID- 16293363
TI  - Uterine fibroid embolization versus myomectomy in women wishing to preserve
      fertility: preliminary results of a randomized controlled trial.
AB  - OBJECTIVE: To compare the clinical results of surgical and endovascular treatment
      of uterine myomas in young women. STUDY DESIGN: In a university-affiliated,
      tertiary care center a prospective trial was conducted. Sixty-three women,
      wishing to retain fertility, with intramural fibroid(s) larger than 4 cm, were
      randomly selected either for uterine artery embolization or myomectomy.
      Invasiveness, efficacy, and complications of both procedures were compared.
      RESULTS: Thirty embolizations and 33 myomectomies (15 laparoscopic, 18 open) were
      performed. The mean follow-up was 17 months. In embolized patients, there was a
      significantly shorter procedure length (p<0.0001), hospital stay (p<0.001) and
      disability period (p<0.0001), lower CRP (p<0.001) and higher hemoglobin
      (p<0.0001) concentrations the 2nd day after procedure. But there was a higher
      incidence of re-interventions (p<0.01) and a lower rate of total symptomatic
      relief (p<0.1). The groups did not significantly differ in: technical success
      rate, febrile morbidity, FSH levels 6 months after the procedure, and
      complication rates. CONCLUSIONS: Although the reproductive outcomes of uterine
      artery embolization and myomectomy cannot be evaluated at the moment, our first
      results indicate that both methods are clinically successful in the majority of
      cases and are not connected with significant number of serious complications.

PMID- 16293364
TI  - Role of CCAAT/enhancer-binding protein, histone acetylation, and coactivator
      recruitment in the regulation of malic enzyme transcription by thyroid hormone.
AB  - In chick embryo hepatocytes, activation of malic enzyme gene transcription by
      triiodothyronine (T3) is mediated by a T3 response unit (T3RU) that contains five
      T3 response elements (T3REs) plus five accessory elements that enhance T3
      responsiveness conferred by the T3REs. Results from in vitro binding assays
      indicate that one of the accessory elements (region F) binds CCAAT/enhancer
      binding protein-alpha (C/EBPalpha). Here, we investigated the role of C/EBPalpha
      in the regulation of malic enzyme transcription by T3. Transfection analyses
      demonstrated that the stimulation of T3RE function by region F did not require
      the presence of additional malic enzyme gene promoter sequences. Expression of a
      dominant negative C/EBP inhibited the ability of region F to stimulate T3
      responsiveness. In chromatin immunoprecipitation assays, C/EBPalpha and TR
      associated with the malic enzyme T3RU in the absence and presence of T3 with the
      extent of the association being greater in the presence of T3. These observations
      indicate that C/EBPalpha interacts with TR on the malic enzyme T3RU to enhance T3
      regulation of malic enzyme gene transcription. T3 treatment increased the
      acetylation of histones, decreased the recruitment of nuclear receptor
      corepressor and increased the recruitment of steroid receptor coactivator-1, CREB
      binding protein, and the thyroid hormone associated protein/mediator complex at
      the malic enzyme T3RU. In contrast, T3 treatment had no effect on the acetylation
      of histones and the recruitment of corepressors and coactivators at the T3RU that
      mediates the T3 activation of acetyl-CoA carboxylase-alpha gene transcription. We
      propose that differences between the malic enzyme T3RU and the ACCalpha T3RU in
      the ability of T3 to modulate histone acetylation and coregulatory protein
      recruitment are due to differences in the composition of the nuclear receptor
      complexes that bind these regulatory regions.

PMID- 16293366
TI  - Chronic antidepressant treatment modulates the release of somatostatin in the rat
      nucleus accumbens.
AB  - This study investigated the in vivo neuronal release of somatostatin in the rat
      nucleus accumbens (NAc), and the effect of chronic administration of
      antidepressants. Microdialysis studies were performed on male Sprague-Dawley
      rats, in accordance with the EU guidelines (EEC Council 86/609). Somatostatin
      levels were quantified by radioimmunoassay (RIA) or enzyme linked immuno sorbent
      assay (ELISA). A high concentration of potassium ions (K(+), 100 mM) was used to
      ascertain the neuronal release of somatostatin. Antidepressant treatments
      involved the administration of citalopram (20 mg/2 ml/kg, i.p., once daily) or
      desipramine (DMI, 5 mg/2 ml/kg, i.p., twice daily) for 21 days. Control groups
      received saline (2 ml/kg for 21 days, i.p.) once or twice daily respective of the
      antidepressant treatment. Basal levels of somatostatin released were found to be
      20.01+/-0.52 fmol/sample. K(+) (100 mM) increased somatostatin levels at 205% of
      basal. Chronic citalopram and desipramine treatments also increased the
      somatostatin levels by 83+/-32% and 40+/-6% of basal, respectively. These
      findings indicate that somatostatin is released neuronally in the NAc.
      Antidepressants influence its release in a positive manner, suggesting the
      necessity of further studies for the elucidation of the involvement of
      somatostatin in the putative therapeutic effects of these agents.

PMID- 16293365
TI  - Thermogenesis in brown adipose tissue: increase by 5-HT2A receptor activation and
      decrease by 5-HT1A receptor activation in conscious rats.
AB  - Body temperature is decreased by 5-hydroxytryptamine 1A (5-HT1A) agonists and
      increased by 5-HT2A agonists. The present study determined whether changes in
      interscapular brown adipose tissue (iBAT) thermogenesis contribute to these
      effects in conscious unrestrained animals. Male Sprague-Dawley rats were pre
      instrumented for measurement of iBAT and core temperature and tail artery blood
      flow one week before experiments. In the first series of experiments, rats were
      transferred from warm (25-28 degrees C) to cold (5-10 degrees C) environments.
      This increased iBAT temperature (+1.3 +/- 0.2 degrees C, P<0.01, n = 7) and
      reduced tail artery flow. Injection of the 5-HT1A agonist, 8-OH-DPAT (8-hydroxy-2
      (di-n-propylamino)tetralin, 0.5 mg/kg, s.c.) reversed the increase in iBAT
      thermogenesis (-1.5 +/- 0.4 degrees C, P<0.01, n = 6), and decreased core
      temperature (-1.5 +/- 0.4 degrees C, P<0.01, n = 6). Pre-treatment with WAY
      100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2
      pyridinyl)cyclohexanecarboxamide trihydrochloride), a 5-HT1A antagonist,
      prevented effects of 8-OH-DPAT. In the second series of experiments, injection of
      a 5-HT2A agonist, DOI (R(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
      hydrochloride, 0.1 mg/kg, s.c.) increased both iBAT (+1.9 +/- 0.1 degrees C,
      P<0.01, n = 7) and core temperatures (+1.4+/-0.2 degrees C, P<0.01, n=7), and
      decreased tail artery blood flow. Subsequent injection of SR 46349B (trans-4
      ((3Z)3-[(2-dimethylaminoethyl)oxyimino]-3-(2-fluorophenyl) propen-1-yl)-phenol,
      hemifumarate, 0.5 mg/kg, s.c.), a 5-HT2A antagonist, reduced all these changes.
      Results indicate that activation of 5-HT1A receptors reduces sympathetic outflow
      to BAT and that activation of 5-HT2A receptors increases this outflow. Changes in
      core temperature mediated by brain/spinal pathways regulated by 5-HT1A and 5-HT2A
      receptors reflect coordinated changes in BAT-mediated heat production as well as
      changes in heat dissipation via the thermoregulatory cutaneous vascular beds.

PMID- 16293367
TI  - Comparison of the effects of four Na+ channel analgesics on TTX-resistant Na+
      currents in rat sensory neurons and recombinant Nav1.2 channels.
AB  - Na(+) channel blockers are highly effective analgesics. Among the neuronal Na(+)
      channel subtypes, Nav1.8 is discussed to be of importance for certain pain
      states, and Nav1.8-preferring Na(+) channel blockers should be able to relief
      pain without causing severe effects (due to the restricted expression of this
      channel type). In this study, the effects of four Na(+) channel blockers on rat
      tetrodotoxin-resistant (TTX-r) Na(+) channels (representing mostly Nav1.8) in
      sensory neurons were investigated using the patch-clamp technique in the voltage
      clamp configuration, and compared with those on cells heterologously expressing
      Nav1.2 alpha subunits. The compounds were lidocaine, mexiletine, benzocaine, and
      ambroxol, which are clinically used to treat pain after local or systemic
      administration. The four compounds inhibited resting TTX-r channels concentration
      dependently, with ambroxol being the most effective (IC(50) value: 34.3 microM),
      and benzocaine being the weakest (IC(50) value: 1,901 microM). All compounds
      shifted steady-state inactivation curves to more negative values. Ambroxol
      blocked resting TTX-r channels more potently than Nav1.2, the opposite was the
      case for lidocaine, mexiletine and benzocaine. Based on the drugs' potencies
      found in this study, and the published information on clinically achievable
      plasma levels, the amount of Na(+) channel block to induce analgesia after
      systemic administration was estimated.

PMID- 16293368
TI  - Activation of A1 and A2 noradrenergic neurons in response to running in the rat.
AB  - Since running accompanied with blood lactate accumulation stimulates the release
      of adrenocorticotropic hormone (ACTH), running above the lactate threshold (LT)
      acts as stress (running stress). To examine whether A1/A2 noradrenergic neurons
      that project to the hypothalamus activate under running stress, c-Fos
      immunohistochemistry was used to compare the effects of running with or without
      stress response on A1/A2 noradrenergic neurons. Blood lactate and plasma ACTH
      concentrations significantly increased in the running stress group, but not in
      the running without stress response and control groups, confirming different
      physiological impacts between different intensity of running with or without
      stress. Running stress markedly increased c-Fos accumulation in the A1/A2
      noradrenergic neurons. Running without stress response also induced a significant
      increase in c-Fos expression in the A1/A2 noradrenergic neurons, and the
      percentage of the increase was smaller than that of running stress. The extent of
      c-Fos expression in the A1/A2 noradrenergic neurons correlates with exercise
      intensity, signifying that this neuronal activation is running speed-dependent.
      We thus suggest that A1/A2 noradrenergic neurons are activated in response to not
      only running stress, but also to other physiological running, enhanced by non
      stressful running. These findings will be helpful in studies of specific
      neurocircuits and in identifying their functions in response to running at
      different intensities.

PMID- 16293369
TI  - Antinociceptive effects and synergistic interaction with morphine of intrathecal
      metabotropic glutamate receptor 2/3 antagonist in the formalin test of rats.
AB  - Spinal metabotropic glutamate receptors (mGluRs) have been known to be involved
      in the modulation of nociception. While the antinociceptive effects of the
      mGluR1/5 have been demonstrated, the role of mGluR2/3 for nociception is less
      clear. This study investigated the effects of an intrathecal mGluR2/3 agonist,
      APDC, and a mGluR2/3 antagonist, LY341495, for inflammatory and acute pain in the
      formalin test and thermal stimulation test. We also examined their interaction
      with intrathecal morphine for the antinociceptive effect. APDC had little effect
      on the formalin-induced nociception. In contrast, LY341495 caused a dose
      dependent suppression of the phase 2 flinching response to the formalin stimulus
      without affecting phase 1 flinching response. Furthermore, the suppression of
      pain behavior by LY341495 during phase 2 was reduced significantly by
      pretreatment with APDC. LY341495 and morphine also showed synergistic drug
      interaction for antinociception during phase 2 in the formalin test.

PMID- 16293370
TI  - Increased aquaporin-1 expression in choroid plexus epithelium after systemic
      hyponatremia.
AB  - The expression of aquaporin-1 (AQP1) protein, a water channel, in the choroid
      plexus epithelium was examined in the rat to determine the role of AQP1 in the
      pathophysiology of systemic hyponatremia. Systemic hyponatremia was produced by
      coadministration of 30 ml hypotonic dextrose solution (140 mM) intraperitoneally
      and 3 microg 1-deamino-8-d-arginine vasopressin (dDAVP) subcutaneously. This
      hydration protocol produced severe systemic hyponatremia: 2h after drug
      administration, normonatremic serum osmolarity and Na(+) concentration (296+/
      5mOsm/L and 140+/-5 mM) were reduced to 252+/-5mOsm/L and 117+/-2 mM,
      respectively. AQP1 expression in the third ventricle choroid plexus epithelium
      was determined by using immunohistochemistry and quantitative immunoblot
      analysis. After 2h of systemic hyponatremia, AQP1 expression was significantly
      increased by 28.2+/-2.7% (n=6, P<0.05), whereas it was attenuated to 15.7+/-2.2%
      (n=6, P<0.05) after 6h of systemic hyponatremia. In addition, TUNEL staining
      revealed apoptotic granule cells in the dentate gyrus (DG) adjacent to the third
      ventricle with a peak measured 2h after the start of the systemic hyponatremia
      protocol, while virtually no apoptotic granule cells left 6h after the start of
      the hyponatremic treatment. These findings suggest that AQP1-mediated excessive
      water influx into the brain through the blood-cerebrospinal fluid barrier during
      systemic hyponatremia may elevate the intracranial pressure and result in the
      apoptotic brain cell death. Thus, AQP1 in the choroid plexus may play an
      important role in the pathogenesis of systemic hyponatremia.

PMID- 16293371
TI  - Effect of neonatal hypothyroidism on Ca(2+)-ATPase activity in the rat brain.
AB  - Effect of neonatal hypothyroidism on kinetic properties of Ca(2+)-ATPase from rat
      brain synaptic plasma membranes and microsomes were examined. Neonatal
      hypothyroidism resulted in significant decrease in the enzyme activity in both
      the membrane systems. The synaptic membranes in control group displayed presence
      of one kinetic component whereas a low affinity component became evident in the
      hypothyroid group. In the microsomes, both control as well as hypothyroid groups
      showed presence of two kinetic components with the latter group showing two-fold
      increase in the K(m). The Ca(2+) binding characteristics were generally unaltered
      in the enzyme from both the membrane systems. Our results suggest that impairment
      in the Ca(2+)-ATPase activity together with altered kinetic properties could be
      one of the underlying biochemical mechanisms leading to CNS dysfunction as a
      consequence of thyroid hormone deprivation during critical stages of brain
      development.

PMID- 16293372
TI  - [Primitive skin T cell lymphomas].

PMID- 16293373
TI  - Isolation of Mycoplasma capricolum-like strains from chickens.
AB  - Members of the genus Mycoplasma infect a wide range of hosts, but individual
      Mycoplasma species tend to exhibit a considerable degree of host specificity. We
      characterized Mycoplasma strain 700, isolated from a kidney of a layer hen in
      Spain and Mycoplasma strains ULB-A and ULB-B, isolated from the air sac and from
      the bile of stunted broiler chickens in Slovenia. The serologic examination
      showed that these three strains are antigenically unrelated to all of the
      recognized Mycoplasma species of avian origin, but closely related to the
      ruminant mycoplasma Mycoplasma capricolum subspecies capricolum (M. capricolum).
      The comparison of their 16S rRNA gene sequences with the sequence of M.
      capricolum (California kid) revealed 99.66% sequence identity for the strain 700
      and 99.59% identity for strains ULB-A and ULB-B. Moreover, the predicted DnaK
      sequences of the M. capricolum-like strains, isolated from chickens, were
      identical to DnaK sequences of M. capricolum. Comparison of their dnaK gene
      sequences with M. capricolum showed 99.64% sequence identity for strain 700 and
      99.27% identity for strains ULB-A and ULB-B. In the flock from which M.
      capricolum-like strains ULB-A and ULB-B were isolated, the majority of chickens
      (83% of the chickens examined) raised antibodies reacting with M. capricolum
      antigens. Notably, the infection of chickens with M. capricolum-like strains
      represents an unusual exception to the range of Mycoplasma species host
      specificity.

PMID- 16293375
TI  - Quantitative ultrasound measurements at the calcaneus in natural and surgically
      induced menopause.
AB  - OBJECTIVE: The aim of the study was to assess skeletal status in natural and
      surgically induced menopausal women regarding the presence of previous
      osteoporotic fracture. METHODS: Ninety-three females after bilateral oophorectomy
      in mean age of 56.8+/-8.3y. (48 without and 45 with fracture, groups 1 and 2,
      respectively) and 285 females with natural menopause in mean age of 56.4+/-7.0y
      (176 without and 109 with fracture, groups 3 and 4, respectively) were studied.
      Mean age, age of menopause, years since menopause (YSM), duration of fertile
      period (durFER) and body size did not differ between women after surgical and
      natural menopause and between non-fractured and fractured groups. No additional
      factors known to influence bone metabolism (either diseases or medications) or
      osteoporosis treatment were noted in the subjects studied. Skeletal status was
      evaluated by quantitative ultrasound (QUS) of the calcaneum using the Achilles
      system (Lunar, USA). RESULTS: Calcaneal QUS results were significantly higher: in
      women after natural than surgical menopause (p<0.05), in non-fractured females
      after natural menopause than in non-fractured females after surgical menopause
      (p<0.001) and in women after natural menopause without fracture compared with
      those with fracture (p<0.000001). The same comparisons between fractured groups
      and between women after surgical menopause with and without fracture revealed no
      significant differences. QUS parameters were regressed in a stepwise, multiple
      regression analysis on age, YSM, durFER, weight and height for all groups. In
      group 1, YSM had a negative influence and durFER was a protective factor; in
      group 2, age and durFER were a negative factors and YSM had no influence; in
      group 3, age and YSM were a negative factors (no role of durFER) and in group 4,
      only YSM had a negative influence, and durFER was a protective factor.
      CONCLUSION: Surgical menopause seems to be a risk factor for osteoporotic
      fracture because of low ultrasound values.

PMID- 16293376
TI  - Symptoms of multiple sclerosis in women in relation to sex steroid exposure.
AB  - OBJECTIVE: To investigate if women with multiple sclerosis (MS) experience
      changes in MS symptoms related to pregnancy, the postpartum period, menopause or
      use of oral contraception (OC) or postmenopausal hormone therapy (HT). METHODS:
      Women with diagnosed MS were recruited from registers of all MS patients known in
      two counties of Sweden, respectively. Ninety-four women were recruited in
      Linkoping and 52 in Sundsvall. The women answered a questionnaire with
      categorized alternatives regarding their MS symptoms related to menstruation,
      pregnancy, delivery, menopause and use of OC or HT. RESULTS: Forty percent of the
      women reported worsening of MS symptoms related to menopause, whereas 56%
      reported no change of symptoms and 5% reported decreased symptoms. More than a
      fourth of the women reported decreased symptoms during pregnancy, 64% reported
      unchanged symptoms and 10% reported increased symptoms. Every third woman
      reported increased symptoms after delivery, 59% reported no change and 5%
      reported decreased symptoms. Few women reported changes in MS symptoms in
      relation to use of HT or OC. CONCLUSION: The presented data indicate a
      relationship between high-oestrogen states and ameliorated symptoms whereas low
      oestrogen states seem to relate to a worsening of the disease. A majority of
      women, however, reported no changes in MS symptoms in relation to the different
      oestrogen states.

PMID- 16293374
TI  - Brain cytokine and chemokine mRNA expression in mice induced by intranasal
      instillation with ultrafine carbon black.
AB  - Ambient air ultrafine particles (UFPs) have gained enormous attention to many
      researchers with recent evidence showing them to have more hazardous effects on
      human health than larger ambient particles. Studies focusing the possibility of
      effects on brain are quite limited. To examine the effect of ultrafine carbon
      black (ufCB) on mice brain, we instilled 125 microg of 14 nm or 95 nm CB into the
      nostrils of 8-week-old male BALB/c mice, once a week for 4 weeks. Four hours
      after the last instillation, we collected olfactory bulb and hippocampus and
      detected the expression of cytokine and chemokine mRNA by quantitative real-time
      PCR method. In this study, we found the induction of proinflammatory cytokines
      (interleukin-1 beta and tumor necrosis factor-alpha and chemokines (monocyte
      chemoattractant protein-1/CCL2, macrophage inflammatory protein-1 alpha/CCL3),
      and monokine induced interferon-gamma/CXC chemokine ligand (CXCL9) mRNA in brain
      olfactory bulb, not in the hippocampus of mice instilled with 14 nm ufCB
      intranasally. We suggest that the intranasal instillation of ufCB may influence
      the brain immune function depending on their size. To our knowledge, this is the
      first study to demonstrate region-specific brain cytokine and chemokine mRNA
      induction in mice triggered by intranasal instillation of specific-sized ufCB, in
      a physiologically relevant condition.

PMID- 16293377
TI  - Continuation of hormone replacement therapy in Slovenia: a prospective,
      randomized, controlled trial--1-year follow-up.
AB  - OBJECTIVES: To evaluate the influence of educational intervention on the hormone
      replacement therapy (HRT) continuation rate in Slovenia after the publication of
      WHI results. METHODS: We enrolled 125 early postmenopausal women in a 12-month
      prospective, randomized, controlled, multicentric study in Slovenia. The study
      group women (n=62) attended educational lectures; the control group women (n=63)
      did not. Data were collected from three types of questionnaire: before starting
      HRT, at follow-up visits at 3, 6, 9 and 12 month, after the educational lecture
      (study group). The continuation rate was measured on the basis of women's self
      reports. The results were analyzed according to the "intention-to-treat"
      principle. The Cox proportional hazard model was used for the final analysis.
      RESULTS: A gynecologist's suggestion, climacteric symptoms and quality of life
      were the prevailing reasons for starting HRT. The prevailing factors affecting
      continuation of HRT were: no or irregular previous OC use (hazard ratio 3.7), no
      educational lectures (hazard ratio 2.0) and climacteric disorders as the reason
      for start HRT (hazard ratio 2.1). In the women who discontinued HRT within the
      first 3 months, the fear of endometrial cancer, breast cancer and bleeding
      problems were statistically more significant than other factors (P=0.034). In the
      women who stopped HRT use within 6-12 months, the fear of breast and endometrial
      cancers increased substantially (P=0.002). CONCLUSIONS: Previous OC use and
      educational lectures on menopausal problems and HRT significantly improve the HRT
      continuation rate. The main reason for discontinuing HRT is fear of breast
      cancer, intensified by media.

PMID- 16293378
TI  - Development of parenteral formulations and evaluation of the biological activity
      of the trypanocide drug benznidazole.
AB  - Chagas disease, caused by Trypanosoma cruzi, is a major public health problem in
      Latin America. According to the World Health Organization, around 20 million
      people are infected and another 40 million are at risk of acquiring the disease.
      One of the drugs most frequently used for the treatment of Chagas disease is
      benznidazole (BZL). It is practically insoluble in water (0.4 mg/ml), which
      precludes the preparation of liquid dosage forms, in particular, parenteral
      formulations. Thus, the aim of this work was to investigate the solubilization of
      BZL at two pH values using various cosolvents such as ethyl alcohol, propylene
      glycol, polyethylene glycol 400, benzyl alcohol, diethylene glycol monoethyl
      ether (Transcutol) and surfactants such as polysorbates (Tween) 40 and 80, and
      sodium dioctyl sulfosuccinate (AOT). Solvent systems based on PEG 400, with the
      addition ethyl alcohol and/or potassium biphthalate buffer solution, increased
      the BZL solubility up to 10 mg/ml. These alcoholic vehicles showed no toxicity
      against parasite when assayed at 1%. Physical and chemical stability studies
      showed that the formulations were stable for at least 1.5 years. In agreement
      with the biological activity results, the selected formulations are suitable for
      further clinical studies. Moreover, increasing the aqueous solubility of BZL
      reduced the problems in vitro testing techniques and bioassays leading to more
      reliable results and/or reproducibility.

PMID- 16293381
TI  - Screening of plants used in Danish folk medicine to treat epilepsy and
      convulsions.
AB  - Aqueous and ethanolic extracts of 42 plants used in Danish folk medicine for the
      treatment of epilepsy and convulsions, or for inducing sedation, were tested for
      affinity to the GABA(A)-benzodiazepine receptor in the flumazenil-binding assay.
      Ethanolic extracts of leaves of Primula elatior and Primula veris and aerial
      parts of Tanacetum parthenium exhibited good, dose-dependent affinity.

PMID- 16293379
TI  - Interactions of oleic acid and model stratum corneum membranes as seen by 2H NMR.
AB  - We have investigated the mechanism through which the penetration enhancer oleic
      acid acts on stratum corneum (SC) model membranes (bovine brain
      ceramide:cholesterol:palmitic acid, 1:1:1 molar ratio). We used solid state
      deuterium nuclear magnetic resonance to monitor such multilamellar SC dispersions
      containing either cholesterol-d(6), palmitic acid-d(31), or oleic acid-d(2) as a
      function of both fatty acid concentration (2:2:1:1 and 1:1:1:1 bovine brain
      ceramide:cholesterol:palmitic acid:oleic acid) and temperature (18-75 degrees C).
      Our results show that below 40 degrees C, oleic acid (OA) is in an 'isotropic'
      phase, indicating that it has not incorporated into the lamellar membrane phase.
      At and above the SC model membrane's crystalline to liquid crystalline melting
      temperature, T(m)=40-42 degrees C, OA interacts with lamellar SC membranes with a
      slight dependence on OA concentration. T(m) does not change upon the exposure of
      the SC model membrane to OA, nor do we see any significant change in membrane
      chain disorder as monitored by the labelled PA. However, the spectra of both the
      palmitic acid (PA) and cholesterol SC model membrane components contain an
      isotropic peak that grows with increasing temperature. Our results thus indicate
      that oleic acid extracts a fraction of the endogenous SC membrane components,
      promoting phase separation in the SC membrane system. Reducing the proportion of
      crystalline lipids and creating more permeable OA-rich domains is a plausible
      mechanism that explains how OA enhances transdermal penetration.

PMID- 16293380
TI  - Traditional Chinese medicine Bao Gan Ning increase phosphorylation of CREB in
      liver fibrosis in vivo and in vitro.
AB  - Previous studies have demonstrated that traditional Chinese medicine Bao Gan
      Ning, which contains six different drugs: Trionyx sinensis Wiegmann shell, Prunus
      persica (L.) Batsch seed, Salvia miltiorrhiza Bge. root, Mallotus opelta (Lour.)
      Muell-Arg root, Astragalus membranaceus (Fisch.) Bge. var. mongho-licus (Bge.)
      Hsiao root and Scutellaria baicalensis Georgi root, was able to protect liver
      against fibrosis in CCL4 models. In an effort to elucidate molecular mechanisms
      by which Bao Gan Ning exerts its anti-fibrosis activity, effects of Bao Gan Ning
      on liver fibrosis and cAMP response element binding protein (CREB), an important
      transcription factor involved in liver fibrosis, were evaluated in animal and
      cell models in this work. Results showed that Bao Gan Ning (2.16 or 4.32
      g/kg/day) significantly decreased alanine aminotransferase (ALT) and
      hyaluronidase levels and reversed liver fibrosis in rat liver fibrosis models.
      The proliferation of HSC-T6, a hepatic stellate cell line, was also significantly
      inhibited by incubation with serums that were prepared from rats fed with Bao Gan
      Ning. Most interestingly, results from Western blot, immunohistochemistry and
      electrophoretic mobility shift assay (EMSA) showed that Bao Gan Ning up-regulated
      CREB phosphorylation both in rat liver fibrosis models and in HSC-T6 cells, but
      did not affect protein level of CREB and the DNA binding activity of CREB. These
      results suggested that up-regulation of CREB phosphorylation may be involved in
      anti-fibrosis activity of Chinese medicine Bao Gan Ning.

PMID- 16293382
TI  - Effects of chronic administrations of aconitine on body weight and rectal
      temperature in mice.
AB  - Aconitine, a major Aconitum alkaloid, is well known for its high toxicity that
      induces severe arrhythmias leading to death. However, aconitine has been used as
      one of the most popular compounds in Shino-Japanese traditional herbal medicine.
      Little has been reported concerned with the long-term effects of aconitine.
      Therefore, the authors investigated the physiological effects of chronic
      administrations of aconitine by determining the changes in body weight and rectal
      temperature of mice, compared with the concentrations of aconitine and its
      metabolites (benzoylaconine and aconine) in the liver and kidneys. The
      concentration ratio of aconitine to the total Aconitum alkaloids (from day 0 to
      22; 90 min after the last administration) gradually decreased, whereas its
      metabolites increased until day 22. The body weight gain in aconitine
      administered group was less than that of the control group until day 22.
      Transient rectal hypothermia occurred within 30 min after the last administration
      of aconitine. Then the rectal temperature gradually increased to normal level in
      respect to time. This study might reveal the possibilities that the drug
      metabolism of aconitine increased and the toxicity of aconitine decreased due to
      long-term administrations of aconitine.

PMID- 16293383
TI  - Propolis: Effect of different concentrations, extracts and intake period on seric
      biochemical variables.
AB  - Propolis is a resinous substance produced by honeybees that possesses many
      biological activities, such as antitumor, antioxidant, antimicrobial, anti
      inflammatory, and immunomodulatory, among others. The purpose of the present
      study was to investigate the biochemical profile of propolis-treated rats to
      observe whether propolis might lead to side effects after administration. Three
      different treatments were analyzed: (1) rats were treated with different
      concentrations of propolis (1, 3 and 6 mg/kg/day) during 30 days; (2) rats were
      treated with 1 mg/kg/day of ethanolic or water extracts of propolis (EEP, WEP)
      during 30 days; (3) rats were treated with 1 mg/kg/day of ethanolic extract of
      propolis during 90 and 150 days. Our results demonstrated no alterations in the
      seric levels of cholesterol, HDL-cholesterol, total lipids, triglycerides and in
      the specific activity of aminotransferases (AST) and lactic dehydrogenase (LDH)
      of propolis-treated groups when compared to controls. On the basis of our
      findings, since propolis does not induce any significant change in seric
      parameters, it is claimed that long-term administration of propolis might not
      have any cardiac injury.

PMID- 16293384
TI  - The effect of linkage on the calculation of DNA match probabilities for siblings
      and half siblings.
AB  - The loci in many forensic multiplexes are often selected to avoid linked loci.
      However as the multiplices used increase in the number of loci represented
      instances are occurring of loci that are loosely linked. As yet little attention
      has been paid to the likely consequence of this. We begin the process of
      developing formulae to give the match probability at two linked loci for full and
      half siblings. The methodology proceeds from the previously published joint IBD
      states for two linked loci [B.K. Suarez, J. Rice, T. Reich, The generalized sib
      pair IBD distribution: its use in the detection of linkage, Ann. Hum. Genet.
      Lond. 42 (1978) 87; J.K. Haseman, R.C. Elston, The investigation of linkage
      between a quantitative trait and a marker locus, Behav. Genet. 2 (1972) 3-19].
      Our formulation has the drawback of assuming linkage equilibrium. This assumption
      may be tenable as a first order approximation. We hope to stimulate work on
      developing better treatments.

PMID- 16293385
TI  - Haplotypes for 13 Y-chromosomal STR loci in South Tunisian population (Sfax
      region).
AB  - Nine Y-STR loci from the "minimal haplotype" (DYS19, DYS385a/b, DYS389I,
      DYS389II, DYS390, DYS391, DYS392, DYS393) included in Y-STR Haplotype Reference
      Databases (YHRD) with 4 additional Y-STRs (DYS436, DYS437, DYS438, DYS439) were
      analyzed by PCR using duplex and Y-PLEX 12 kit, followed by automatic genotyping
      in a sample of 105 Tunisian males originating from Sfax region (south Tunisia).
      Allelic frequencies and gene diversities for each Y-STR locus were determined.
      The high haplotype diversity (0.9932) and discrimination capacity (0.7714) show
      the usefulness of these loci for human identification in forensic studies and
      paternity tests in Tunisia. The most common haplotype was shared by 4.7% (5
      individuals) of the sample was only found in samples from the Tunisian population
      reported in YHRD. One private allele for DYS392 (allele 17) was discovered and
      duplications were observed for five loci (DYS19, DYS389I, DYS393, DYS437 and
      DYS439).

PMID- 16293387
TI  - Olfactory dysfunction in sinusitis with infiltration of numerous activated
      eosinophils.
AB  - OBJECTIVES: To compare the number of activated eosinophils in the ethmoidal sinus
      mucosa with the computed tomographic findings and degree of olfactory
      dysfunction, and study the clinical characteristics of this disease. MATERIAL AND
      METHODS: Ethmoidal sinus mucosal specimens were obtained from 84 patients with
      bilateral sinusitis accompanied by endoscopic sinus surgery (ESS). The percentage
      of activated eosinophils identified by staining with EG2 antibody was compared
      with the nasal symptoms (nasal obstruction, nasal discharge, headache, problems
      of smell and overall), the CT images and the olfactory dysfunction assessed using
      the T&T olfactometry kit and the Alinamin test. In addition, comparison was made
      of the endoscopic findings obtained after the ESS and the results of the T&T
      olfactometry assessment. RESULTS: Specimens from 42 patients were classified in
      the group showing a high percentage of EG2-positive cells, while specimens from
      40 patients were classified in the group showing a low percentage of EG2-positive
      cells. Comparison of the subjective symptoms in these two groups found a
      statistically significant difference only in relation to "problems of smell",
      while comparison of the two groups in terms of the CT scan findings found
      significant differences only in relation to the anterior and posterior ethmoidal
      sinuses. In addition, it was found that there was a possibility of manifestation
      of olfactory dysfunction in the group with a high percentage of EG2-positive
      cells even when the overall CT score was low. Comparison of the postoperative
      ethmoidal sinus endoscopic findings and the results using the T&T Olfactometry
      kit revealed that olfactory dysfunction occurs together with aggravation of the
      lesions. CONCLUSIONS: For the diagnosis of sinusitis accompanied by severe
      infiltration of activated eosinophils, attention should be paid not only to the
      eosinophil counts in the blood and the tissues, but also to the clinical
      findings, such as the status of lesions in the ethmoidal sinus as seen in CT
      scans and the manifestation of olfactory dysfunction.

PMID- 16293386
TI  - Dumping after homicide using setting in concrete and/or sealing with bricks--six
      case reports.
AB  - Homicide with subsequent hiding of the body using setting in concrete or sealing
      with bricks are rarely seen forensic cases. The article describes the
      circumstances and findings of six cases in which bodies were encased with
      concrete and/or bricks. In all cases, the offenders were male, in one case
      together with his wife and--except for one case--the victims were related to the
      offender. The causes of death were heterogeneous (suffocation, blunt force, shot)
      and the motive mainly domestic quarrel. Setting corpses in concrete and/or
      sealing with bricks does not prevent smell, slows decomposition and therefore
      complicates the estimation of the post mortem interval.

PMID- 16293388
TI  - Decorin from different bovine tissues: study of glycosaminoglycan chain by
      PAGEFS.
AB  - The sulphation pattern of glycosaminoglycan (GAG) plays a critical role in
      biological functions of proteoglycans. In this study, we showed that decorins
      from different bovine tissues present specific sulphation pattern coupled with
      peculiar biological activity. In order to elucidate chemical structure of decorin
      glycosaminoglycan chains, we improved an electrophoretic method to analyse
      fluorescent disaccharides from dermatan/chondroitin sulphate GAG chains. The
      disaccharide separation is based on minigels, and this technique was able to
      define the polysaccharide chain composition in terms of sulphated and not
      sulphated disaccharides. This approach allowed not only the measurement of few
      picomoles of material, but it also permits a rapid qualitative analysis of the
      GAG chains. Data obtained by PAGEFS indicate that the sulphation pattern of GAG
      is tissue specific and this finding may explain the different binding properties
      to von Willebrand factor of decorins.

PMID- 16293389
TI  - Simultaneous determination of berberine and palmatine in rat plasma by HPLC-ESI
      MS after oral administration of traditional Chinese medicinal preparation Huang
      Lian-Jie-Du decoction and the pharmacokinetic application of the method.
AB  - A sensitive and specific liquid chromatography-electrospray ionization-mass
      spectrometry (LC-ESI-MS) method has been developed and validated for the
      identification and quantification of berberine and palmatine in rat plasma. After
      the addition of the internal standard (IS) and alkalization with 0.5M sodium
      hydroxide solution, plasma samples were extracted by ethyl ether and separated by
      HPLC on a Shim-pack ODS (4.6 microm, 150 mm x 2.0mm i.d.) column using a mobile
      phase composed of A (0.08% formic acid and 2 mmol/l ammonium acetate) and B
      (acetonitrile) with linear gradient elution. Analysis was performed on a Shimadzu
      LC/MS-2,010A in selected ion monitoring (SIM) mode with a positive electrospray
      ionization (ESI) interface. [M](+)=336 for berberine; 352 for palmatine and
      [M+H](+)=340 for IS were selected as detecting ions, respectively. The method was
      validated over the concentration range of 0.31-20 ng/ml for berberine and
      palmatine. Inter- and intra-CV precision (R.S.D.%) were all within 15% and
      accuracy (%bias) ranged from -5 to 5%. The lower limits of quantification were
      0.31 ng/ml for both analytes. The extraction recovery was on average 68.6% for
      berberine, 64.2% for palmatine. The validated method was used to study the
      pharmacokinetic profile of berberine and palmatine in rat plasma after oral
      administration of Huang-Lian-Jie-Du decoction.

PMID- 16293390
TI  - Activation of oxazaphosphorines by cytochrome P450: application to gene-directed
      enzyme prodrug therapy for cancer.
AB  - Cancer chemotherapeutic prodrugs, such as the oxazaphosphorines cyclophosphamide
      and ifosfamide, are metabolized by liver cytochrome P450 enzymes to yield
      therapeutically active, cytotoxic metabolites. The effective use of these
      prodrugs is limited by host toxicity associated with the systemic distribution of
      cytotoxic metabolites formed in the liver. This problem can, in part, be
      circumvented by implementation of cytochrome P450 gene-directed enzyme prodrug
      therapy (P450 GDEPT), a prodrug activation strategy for cancer treatment that
      augments tumor cell exposure to cytotoxic drug metabolites generated locally by a
      prodrug-activating cytochrome P450 enzyme. P450 GDEPT has been exemplified in
      preclinical rodent and human tumor models, where chemosensitivity to a P450
      prodrug can be greatly increased by introduction of a prodrug-activating P450
      gene. Further enhancement of the efficacy of P450-based gene therapy can be
      achieved: by co-expression of P450 with the flavoenzyme NADPH-P450 reductase,
      which provides electrons required for P450 metabolic activity; by metronomic
      (anti-angiogenic) scheduling of the prodrug; by localized delivery of the prodrug
      to the tumor; and by combination with anti-apoptotic factors, which slow the
      death of the P450 'factory' cells and thereby enhance the bystander cytotoxic
      response. P450 GDEPT has several important features that make it a clinically
      attractive strategy for cancer treatment. These include: the substantial
      bystander cytotoxicity of P450 prodrugs such as cyclophosphamide and ifosfamide;
      the ability to use human P450 genes and thereby avoid an immune response to the
      therapeutic gene; the use of well-established conventional chemotherapeutic
      prodrugs, as well as bioreductive drugs activated by P450/P450 reductase in a
      hypoxic tumor environment; and the potential to decrease systemic exposure to
      active drug metabolites by selective inhibition of hepatic P450 activity. Recent
      advances in this area of research are reviewed, and two proof-of-concept clinical
      trials that highlight the utility of this strategy are discussed.

PMID- 16293391
TI  - Comparative study of red blood cell method in rat and calves blood as
      alternatives of Draize eye irritation test.
AB  - INTRODUCTION: Red blood cell assay (RBC) is used to estimate potential irritation
      of tensioactive agents and detergents. Cell membrane lysis and cell protein
      denaturation are measured photometrically. This study was aimed to determine if
      rat blood cells can be used to predict eye potential irritation in the same way
      of calves blood cells in RBC assay. METHODS: We evaluated 20 cosmetic
      formulations using rat and calves blood according to INVITOX protocol No 37. Data
      of media hemolysis concentration, denaturation index and the ratio of both
      parameters were compared with in vivo data of eye irritancy. RESULTS: There was a
      significant difference (p<0.01) between H50 value when evaluated the standard SDS
      with red blood cell method in rat and calves blood. According to the exact
      probability of Fisher taking as approach the acceptance or rejection of the
      substance there are no significant differences between in vitro assay with calves
      blood and in vivo results. Not happening the same way for the RBC assay with rat
      blood where significant differences were obtained (p<0.01) among the
      classification of in vitro and in vivo test. DISCUSSION: The RBC assay using
      calves blood showed better results. Several test substances were false negatives
      with rat blood. This high false negative rate would be correctly identified by
      the animal test but it may also lead to increased animal consumption. For that
      RBC assay with calf blood cells is preferable to the employment of rat blood as
      screening method with a reduction and refinement strategy.

PMID- 16293392
TI  - The complex history of distal human chromosome 1q.
AB  - Human chromosome 1 has been claimed to be a conserved ancestral chromosome of
      eutherian mammals. However, two small regions from distal 1q (with orthology to
      mouse chromosome 11) appear to have a different history. These two regions are
      proposed to have been added to the ancestor of human chromosome 1 as a single
      block that was subsequently disrupted by a paracentric inversion. The
      translocation and inversion appear to have occurred at some time after the
      primate lineage diverged from a common ancestor with rodents. Reconstruction of
      the history of distal human chromosome 1q is complicated by the "reuse" of
      breakpoints in different mammalian lineages and by coincidental shared synteny
      between humans and cats.

PMID- 16293393
TI  - Identifying immune traits and biobehavioral correlates: generalizability and
      reliability of immune responses in rhesus macaques.
AB  - Variation in immune responses over time and in different contexts presents a
      methodological challenge for characterizing the typical immune status of an
      individual. Our analyses statistically evaluated sampling strategies for
      optimizing the determination of an "immune trait" in studies of individual
      differences with nonhuman primates. Lymphocyte proliferation and natural killer
      cell activity were assessed on multiple occasions at 3-week intervals in male
      rhesus macaques for up to 1 year while they lived in undisturbed conditions.
      Generalizability and Monte Carlo analyses were utilized to explore the benefits
      of multiple evaluations and the effects of reliability on replication. There were
      substantial gains in reliability and stability by obtaining 4 or more immune
      assessments of the same individual, and the benefits continued to accrue to an
      optimal assessment level of 10 or more evaluations for each individual. The value
      of determining "immune traits" was then exemplified by demonstrating the degree
      to which the monkeys' handedness correlated with reliable indices of
      proliferative and cytolytic responses averaged over 1 year of assessment.

PMID- 16293394
TI  - Trait positive affect and antibody response to hepatitis B vaccination.
AB  - Recent evidence suggests that dispositional positive affect may be associated
      with decreased vulnerability to upper respiratory infections. To explore a
      potential pathway of this relationship, we examined whether trait positive affect
      is related to an in vivo immune response relevant for host resistance to
      infection. Eighty-four healthy, graduate students who tested negative for prior
      expose to the hepatitis B virus were administered the standard hepatitis B
      vaccination series. Five months after the first dose, a blood sample was
      collected for the measurement of specific antibody response to the vaccine and
      subjects completed a battery of psychosocial questionnaires. Higher scores on a
      measure of dispositional positive affect were associated with a greater antibody
      response to hepatitis B vaccination. This relationship occurred after controlling
      for demographics and body mass and was largely independent of concomitant levels
      of dispositional negative affect, optimism, and extraversion. In the presence of
      dispositional positive affect, there was no independent effect of trait negative
      affect on antibody response. Physical activity played a protective role for
      individuals low in positive affect, being related to higher antibody responses.
      These data provide initial evidence that individual differences in dispositional
      positive affect may be of health significance, being related to an in vivo immune
      response relevant for protection against infection.

PMID- 16293395
TI  - Bromochloro-haloacetic acids: effects on mouse embryos in vitro and QSAR
      considerations.
AB  - The haloacetic acids (HAA) are a family of chemicals that are drinking water
      disinfection by-products. We previously reported that haloacetic acids, including
      several bromo- and chloro-HAAs, alter embryonic development when mouse
      conceptuses are directly exposed to these xenobiotics in whole embryo culture.
      Craniofacial dysmorphogenesis was observed in exposed embryos and a quantitative
      structure activity relationship (QSAR) for induction of cranial neural tube
      dysmorphogenesis was established for a series of 10 HAAs, which also included
      fluoro- and iodo-HAA representatives. In the current study, we evaluate the
      effects of exposing neurulation staged (3-6 somite pairs) CD-1 mouse conceptuses
      to bromochloro- (BCA), dibromochloro- (DBCA) and bromodichloro-acetic (BDCA)
      acids in whole embryo culture at concentrations ranging from 50 to 2500 microM.
      Morphological development was assessed after a 26 h exposure period. Exposure of
      conceptuses to these HAAs produced dysmorphogenesis, including prosencephalic and
      pharyngeal arch hypoplasia as well as eye and heart tube abnormalities. Benchmark
      concentrations for induction of neural tube dysmorphogenesis were 63, 500 and 536
      microM for BCA, DBCA and BDCA, respectively. Our previously developed HAA QSAR
      accurately predicted placement of these three chemicals in the larger context of
      the previously tested di- and tri-HAAs, also correctly predicting that BCA would
      be more potent than DBCA and BDCA, and that the latter two HAAs would be near
      equi-potent. This study describes the concentration-dependent induction of
      dysmorphogenesis in whole embryo culture by three mixed chloro/bromo-HAAs and
      demonstrates the ability of the HAA QSAR to predict relative potencies within
      this family of xenobiotics.

PMID- 16293397
TI  - Progressive vocal cord dysfunction subsequent to a chlorine gas exposure.
AB  - Chlorine gas inhalation, similar to other toxic gas exposures, can impart a
      variety of effects to the entire airway ranging from mucous membrane irritation
      to acute respiratory distress syndrome. The extent and location of damage is
      determined by numerous situational factors such as the duration of exposure,
      quantity of gas released, environmental factors, and instituted chemical defense
      measures. Reactive airways dysfunction and nonspecific bronchial
      hyperresponsiveness are commonly reported as sequelae to chlorine exposure. This
      article constitutes the first case of a single antecedent chlorine exposure
      inducing progressive vocal cord dysfunction.

PMID- 16293396
TI  - The effectiveness of a voice treatment approach for teachers with self-reported
      voice problems.
AB  - SUMMARY: Teachers are considered the professional group most at risk of
      developing voice-problems, but limited treatment effectiveness evidence exists.
      We studied prospectively the effectiveness of a 6-week combined treatment
      approach using vocal function exercises (VFEs) and vocal hygiene (VH) education
      with 20 teachers with self-reported voice problems. Twenty subjects were randomly
      assigned to a no-treatment control (n = 11) and a treatment group (n = 9).
      Fibreoptic endoscopic evaluation was carried out on all subjects before
      randomization. Two self-report voice outcome measures were used: the Voice
      Related Quality of Life (VRQOL) and the Voice Symptom Severity Scale (VoiSS). A
      Voice Care Knowledge Visual Analogue Scale (VAS), developed specifically for the
      study, was also used to evaluate change in selected voice knowledge areas. A
      Student unpaired t test revealed a statistically significant (P < 0.05)
      improvement in the treatment group as measured by the VoiSS. There was not a
      significant improvement in the treatment group as measured by the V-RQOL. The
      difference in voice care knowledge areas was also significant for the treatment
      group (P < 0.05). This study suggests that a voice treatment approach of VFEs and
      VH education improved self-reported voice symptoms and voice care knowledge in a
      group of teachers.

PMID- 16293398
TI  - Perforator flaps in head and neck surgery.
AB  - A 'perforator flap' is a flap of skin or subcutaneous tissue that is based on the
      dissection of a 'perforating vessel'. Over the past few years a large number of
      'perforator flaps' have been devised and described. By reducing any muscle
      harvest and trauma to a minimum, perforator flaps aim to minimize donor site
      morbidity whilst providing the reconstructive surgeon with more versatility than
      other flap types. The principal perforator flaps are discussed, particularly
      those employed in head and neck reconstruction including 'free style perforator
      flaps'. Methods of locating perforating vessels for the use of perforator flaps
      are described. The technique of perforator flap harvest is illustrated as
      exemplified in the anterolateral thigh perforator flap. Advantages in the use of
      this flap for head and neck reconstruction are discussed and are compared with
      that of non-perforator flaps, particularly the Radial Forearm Flap. The role of
      the primary thinning of perforator flaps is discussed. The versatility of the
      anterolateral flap is discussed, which may well supersede the Radial Forearm Flap
      as the principal soft tissue flap used in head and neck surgery.

PMID- 16293399
TI  - How to broaden enzyme substrate specificity: strategies, implications and
      applications.
AB  - For identification of mutations associated with the broadening of enzyme
      substrate specificity, three strategies, including directed enzyme evolution, are
      described for selected examples. Implications concerning enzyme models are
      highlighted. Applications to the field of biocatalysis are discussed. A
      bidimensional map for the classification of enzyme activities is suggested so as
      to improve genome annotations.

PMID- 16293400
TI  - A combined 17O RAPT and MQ-MAS NMR study of L-leucine.
AB  - We report the application of rotor-assisted population transfer (RAPT) to measure
      the quadrupolar coupling constant (C(q)) for spin 5/2 nuclei. Results from
      numerical simulations are presented on the magnitude of enhancement factor as a
      function of frequency offsets, i.e. the RAPT profile. Experimental O17 RAPT
      profile is traced for the amino acid L-leucine. In addition, results from MQ-MAS
      experiments are incorporated to determine the quadrupolar asymmetry parameter
      (eta(q)). Unlike previous reports, the O17 NMR parameters for an amino acid, L
      leucine, is reported at a relatively low field of 9.4 T.

PMID- 16293401
TI  - Characterization of dehydration and hydration behavior of calcium lactate
      pentahydrate and its anhydrate.
AB  - The use of calcium lactate pentahydrate (CLP) as an additional filler-binder for
      direct compaction of tablets has been reported to result in a short
      disintegration time and rapid drug release. The aim of this study was to
      understand the dehydration and hydration behavior of CLP and calcium lactate
      anhydrate (CLA) under various conditions of storage temperature and relative
      humidity. The removal and acquisition of crystal water were investigated by using
      differential scanning calorimetry (DSC), thermogravimetry-differential thermal
      analysis (TG-DTA), powder X-ray diffraction (PXRD) and scanning electron
      microscopy (SEM). The PXRD results indicated that CLP exists as a crystalline
      solid and CLA as an amorphous solid. Dehydration of CLP resulted in aggregated
      particles of CLA with an increase in average particle size. The dehydration and
      hydration kinetics of CLP were analyzed with the Hancock-Sharp equation on the
      basis of the isothermal DSC data. The dehydration of CLP followed a zero-order
      mechanism (Polany-Winger equation). In contrast, the surface roughness of CLA was
      significantly decreased by hydration. The hydration of CLA followed a three
      dimensional diffusion model (Ginstling-Brounshtein equation).

PMID- 16293402
TI  - Neural processes underlying conscious perception: experimental findings and a
      global neuronal workspace framework.
AB  - One striking property of perception is that it can be achieved in two seemingly
      different ways: either consciously or non-consciously. What distinguishes these
      two types of processing at the neural level? So far, empirical findings suggest
      that conscious perception is associated with an increase in activity at the
      sensory level, the specific involvement of a fronto-parietal network and an
      increase in long-distance functional connectivity and synchrony within a broad
      network of areas. We interpret these data in the framework of the global neuronal
      workspace model which proposes that the neural basis of conscious access is a
      sudden self-amplifying process leading to a global brain-scale pattern of
      activity. In contradiction with several theories which assume that there is a
      continuum of perception, associated with a gradual change in the intensity of
      brain activation, the model predicts a sharp non-linear transition between non
      conscious and conscious processing.

PMID- 16293404
TI  - Post-moderate exercise testing and clinical predictive value of ankle arm index
      measurements.
AB  - Since peripheral vascular disease (PVD) is the forerunner of coronary heart
      disease (CHD), it is vital to detect PVD at an early stage. In the past, the non
      invasive ankle arm index (AAI) has been successfully used to predict the
      susceptibility of PVD/CHD. However, different authors have used different
      permutations (i.e. highest, average and lowest) of ankle (ASBP) and arm (HSBP)
      systolic blood pressures to calculate AAI. This study aims to investigate the
      validity and applicability of different permutations of AAI formulae to predict
      sub-clinical PVD/CHD in young individuals. The study also investigated whether
      the use of AAI post-moderate exercise would enhance the predictability of PVD or
      CHD at an early stage. Individuals from different ethnic background within the UK
      took part in this study. Following 5min moderate cycle exercise using 50% of
      heart reserve, the AAI was significantly reduced (P<0.05). It was found that not
      all the permutations of AAI were acceptable and some over/under estimated AAI
      compared to currently accepted methodologies. According to the statistical
      analysis (ANOVA and 95% limits of agreement) calculation of AAI using values of
      (1) highest ASBP divided by highest HSBP, (2) highest ASBP divided by average
      HSBP, (3) average ASBP divided by highest HSBP and (4) lowest ASBP divided by
      average HSBP were within acceptable agreement with the standard method of
      calculating AAI. Inclusion of these permutations together with the standard
      method, would give a better predictions of PVD/CHD at an early age.

PMID- 16293403
TI  - Sound processing in the auditory-cortex homologue of songbirds: functional
      organization and developmental issues.
AB  - Recent literature on the Field L of songbirds, showing that some neurons present
      a clear selectivity towards complex sounds, especially conspecific songs, is
      reviewed. Furthermore, studies on European starlings have revealed a complex
      functional organization in this central auditory area, with subareas exhibiting
      different response features. Interestingly, both the functional organization and
      the neuronal specialization can be drastically affected by early deprivation,
      clearly showing the existence of a developmental plasticity. Some recovery seems
      to remain possible at later stages, and social factors may be involved.

PMID- 16293405
TI  - Recovery of municipal waste incineration bottom ash and water treatment sludge to
      water permeable pavement materials.
AB  - Water treatment plant sludge and municipal solid waste incinerator bottom ash are
      non-hazardous residues, and they can be reprocessed to produce useful materials
      for city public works. In this study, an effort was endeavored to investigate the
      properties of water permeable bricks made of water treatment sludge and bottom
      ash without involving an artificial aggregate step. The water treatment plant
      sludge was dried and ground, and the bottom ash was subjected to magnetic
      separation to remove ferrous metals. Both sludge and bottom ash were ground and
      sieved to a size of <2mm. Different contents of water treatment sludge (70-95% by
      weight) were mixed with bottom ash and the blocks were molded under a pressure of
      110 kg/cm2. Thereafter, the molded blocks were sintered at temperatures of 900
      1200 degrees C for 60-360 min. The compressive strength, permeability and water
      absorption rate of the sintered brick were examined and compared to relevant
      standards. The amount of bottom ash added in the mixture with water treatment
      sludge affects both the compressive strength and the permeability of the sintered
      bricks. The two effects are antonymous as higher bottom ash content will develop
      a beehive configuration and have more voids in the brick. It is concluded that a
      20% weight content of bottom ash under a sintering condition of 1150 degrees C
      for 360 min can generate a brick with a compressive strength of 256 kg/cm2, a
      water absorption ratio of 2.78% and a permeability of 0.016 cm/s.

PMID- 16293406
TI  - A full-scale study of treatment of pig slurry by composting: kinetic changes in
      chemical and microbial properties.
AB  - Since the indiscriminate disposal of pig slurry can cause not only air pollution
      and bad odours but also nutrient pollution of ground waters and superficial
      waters, composting is sometimes used as one environmentally acceptable method for
      recycling pig manure. The aim of this study was to evaluate the effect of
      composting pig slurry on its sanitation (evaluated by ecotoxicity assays and
      pathogen content determination), as well as to determine the effect of a carbon
      rich bulking agent (wood shavings, WS) and the starting C/N ratio on the changes
      undergone by different chemical (volatile organic matter, C and N fractions) and
      microbiological (microbial biomass C, ATP, dehydrogenase activity, urease,
      protease, phosphatase, and beta-glucosidase activities) parameters during
      composting. Pig slurry mixed with bulking agent (P+WS) and the solid faction
      separated from it, both with (PSF+WS) and without bulking agent (PSF), were
      composted for 13 weeks. Samples for analysis were taken from composting piles at
      the start of the process and at 3, 6, 9, and 13 weeks after the beginning of
      composting. The total organic carbon, water soluble C and ammonium content
      decreased with composting, while Kjeldahl N and nitrate content increased. The
      nitrification process in the PSF+WS pile was more intense than in the PSF or P+WS
      composting piles. The pathogen content decreased with composting, as did
      phytotoxic compounds, while the germination index increased with compost age.
      Piles with bulking agent showed higher values of basal respiration, microbial
      biomass carbon, ATP and hydrolase activities during the composting process than
      piles without bulking agent.

PMID- 16293407
TI  - Fungal survival during anaerobic digestion of organic household waste.
AB  - Anaerobic digestion of organic waste yields energy rich biogas and retains
      nutrients (N, P, K, S, etc.) in a stabilised residue. For the residue to be used
      as a soil fertiliser, it must be free from pollutants and harmful microorganisms.
      Fungal survival during sanitation and anaerobic treatment of source-separated
      organic household waste and during aerobic storage of the residue obtained was
      investigated. Decimal reduction times were determined for inoculated fungi
      (Aspergillus flavus and Aspergillus fumigatus, Penicillium roqueforti, Rhizomucor
      pusillus, Thermoascus crustaceus and Thermomyces lanuginosus). Several different
      fungal species were found after waste sanitation treatment (70 degrees C, 1 h),
      with Aspergillus species dominating in non-inoculated waste. Anaerobic waste
      degradation decreased the diversity of fungal species for processes run at both
      37 and 55 degrees C, but not total fungal colony forming units. Fungi surviving
      the mesophilic anaerobic digestion were mainly thermotolerant Talaromyces and
      Paecilomyces species. T. crustaceus and T. lanuginosus were the only inoculated
      fungi to survive the thermophilic anaerobic degradation process. Aerobic storage
      of both types of anaerobic residues for one month significantly decreased fungal
      counts.

PMID- 16293409
TI  - Adjuvant chemotherapy for non-small cell lung cancer: ready for clinical
      practice?
AB  - Radical surgery remains the only treatment with curative potential for patients
      with operable non-small cell lung cancer (NSCLC). However, despite complete
      surgical resection, long-term survival is still disappointing with an average 5
      year survival rate lower than 60%. Thoracic post-operative radiotherapy trials
      demonstrated a possible impact in reducing loco-regional recurrence but not
      overall survival. Moreover, the majority of post-surgical failures are
      represented by distant metastases, indicating a possible role for adjuvant
      systemic therapies. The role of adjuvant chemotherapy has now been clearly
      established in many solid tumors and the role of last generation platinum-based
      chemotherapy has now being considered as standard of care in advanced NSCLC.
      However, the role of adjuvant chemotherapy for completely resected NSCLC remains
      highly controversial. After the meta-analysis published in 1995, which showed a
      non-statistically significant 5% improvement in 5-year survival with second
      generation platinum-based adjuvant chemotherapy, several randomized clinical
      trials addressing the role of last generation adjuvant chemotherapy in patients
      with completely resected stage I, II and IIIA NSCLC have been completed with
      conflicting results. The available scientific evidence is reviewed and
      strengths/weaknesses of each trial are discussed in this article. Although most
      of the available evidence points to a possible survival benefit in long-term
      survival improvement ranging from 4% to 15%, the introduction of adjuvant
      chemotherapy as standard of care in the treatment of resected NSCLC is still a
      matter of debate. Practical issues and clinical aspects which may help clinicians
      in the decision making process about prescription of adjuvant treatment are also
      discussed.

PMID- 16293408
TI  - A high sensitivity amperometric biosensor using laccase as biorecognition
      element.
AB  - An amperometric flow biosensor, using laccase from Rigidoporus lignosus as
      bioelement was developed. The laccase was kinetically characterized towards
      various phenolics both in solution and immobilized to a hydrophilic matrix by
      carbodiimide chemistry. A bioreactor connected to an amperometric flow cell by a
      FIA system was filled with the immobilized enzyme and the operational conditions
      of this biosensor were optimized as regards pH. Under the adopted experimental
      conditions, the immobilized enzyme oxidizes all the substrate molecules avoiding
      the need of cumbersome calibration procedures. The biosensor sensitivity, which
      was found to be 100 nA/microM for some of the tested substrates, resulted to be
      constant for more than 100 working days. This biosensor permits the detection of
      phenolics in aqueous solutions at concentrations in the nanomolar range and was
      successfully used to detect phenolics in wastewaters from olive oil mill without
      sample preparation.

PMID- 16293410
TI  - Incidence of gastrointestinal stromal tumours is underestimated: results of a
      nation-wide study.
AB  - Gastrointestinal stromal tumours (GIST) are identified by their specific
      morphology added with immunohistochemical staining with anti-CD117, the
      phenotypic marker for GIST in the majority of cases. In this study the reported
      incidence of GIST and GIST-like tumours before and after the routine availability
      of the specific diagnostic marker CD117 antigen was investigated. All patients
      with GIST or GIST-like tumours were selected from PALGA, a nation-wide network
      and registry of histo- and cytopathology in the Netherlands, to calculate the
      incidence in 1995 and longitudinally over time between 1998 and 2003.
      Pathological reports were retrieved to assess the type of immunostaining used and
      to assess the risk category for malignant behaviour according to the recently
      published consensus criteria. The annual incidence of GIST as distilled from the
      national pathology registry increased from 2.1 per million inhabitants in 1995 to
      12.7 per million inhabitants in 2003. The incidence of GIST-like tumours
      decreased from 17.6 per million inhabitants in 1995 to 12.7 per million
      inhabitants in 2003. The incidences were stable from 2000 onwards. Additional
      analysis in 2003 indicated that more than 90% of the GIST tested was CD117
      positive, compared to only 4% of the GIST-like tumours. Almost 50% of the GIST
      was considered to be at high-risk for malignant behaviour, according to the
      consensus criteria. The increased incidence of GIST 1995-2003 is related to
      increased understanding of GIST pathobiology and the routine availability of the
      diagnostic immunohistochemical antibody directed against the CD117 antigen.

PMID- 16293411
TI  - Peripheral neuropathy: a persisting challenge in paclitaxel-based regimes.
AB  - Cumulative peripheral neuropathy (PNP) still remains a limitation to optimal
      treatment with paclitaxel (PAC), especially in more dose-dense schedules. This
      primary sensory PNP may affect the majority of patients after administration of
      certain cumulative dosages of PAC, while the exact mechanisms of PAC-induced PNP
      are not known. While a number of preclinical models revealed its vehicle
      Cremophor EL (CrEL) to be mainly responsible for ganglionopathy, axonopathy and
      demyelination, clinical data also supports a strong and independent effect of PAC
      itself, which is most likely based on disturbances in the microtubules in
      perikaryons, axons and glia cells. Indeed, clinical trials of CrEL-free
      formulations of PAC still report grade III neurotoxicity as dose-limiting. As
      treatment options of PAC-induced PNP are rare the use of specific scoring systems
      for screening purposes is strongly encouraged. In this report we review and
      discuss the pathogenesis, incidence, risk factors, diagnosis, pharmacodynamics
      and treatment options for PAC-induced PNP.

PMID- 16293412
TI  - Dydrogesterone in threatened abortion: pregnancy outcome.
AB  - OBJECTIVE: To determine whether therapy with dydrogesterone in threatened
      abortion during the first trimester of pregnancy will improve pregnancy outcome.
      DESIGN: Prospective open study. SUBJECTS: Pregnant women presenting to the
      obstetric and gynaecology clinic admitting center with vaginal bleeding before 13
      weeks gestation were evaluated for entry into the study. Women were excluded if
      they had a history of recurrent miscarriage. METHOD: Eligible subjects were
      randomized to receive either dydrogesterone 40 mg stat dose followed by 10 mg
      twice a day for one week or conservative therapy. RESULTS: One hundred and 54
      women were recruited. There was no statistically significant differences between
      the two groups with regard to pre-treatment status. The continuing pregnancy
      success rate was significantly (p=0.037) higher in women treated with
      dydrogesterone (95.9%) compared with women who received conservative treatment
      (86.3%). The odds ratio of the success rate between dydrogesterone treatment and
      non-treatment was 3.773 (95% confidence interval: 1.009-14.108). CONCLUSION:
      Corpus luteal support with dydrogesterone has been shown to reduce the incidence
      of pregnancy loss in threatened abortion during the first trimester in women
      without a history of recurrent abortion.

PMID- 16293413
TI  - Acid-hydrolysis of fish wastes for lactic acid fermentation.
AB  - In this study, two acid-hydrolysis processes, process A and process B, were
      proposed to produce low-cost nutrients for the production of lactic acid. Process
      A was a direct way to hydrolyze protein with diluted acid while process B was
      process A plus fish wastes pretreatment (an extraction by water). The two methods
      could both treat fish wastes to be suitable nutrient sources for promoting lactic
      acid production. As the pretreatment indicated some favorable effect on fish
      waste hydrolyzate (FWH), process B increased lactic acid productivity by 22%.
      Compared with 20 g/L yeast extract (YE), 6.8% FWH hydrolyzed by process B had
      more efficiency in lactic acid production, indicating that process B was suitable
      to produce high performance nutrients for lactic acid production and FWH
      hydrolyzed by process B would be an substitute for YE.

PMID- 16293414
TI  - Accumulation of Acid Orange 7, Acid Red 18 and Reactive Black 5 by growing
      Schizophyllum commune.
AB  - The effect of Acid Orange 7, Acid Red 18 and Reactive Black 5 on the growth and
      decolorization properties of Schizophyllum commune was studied with respect to
      the initial pH varying from 1 to 6 and initial dye concentration (10-100 mg/L).
      The optimum pH value was found to be 2 for both growth and color removal of these
      azo dyes. Increasing the concentration of azo dyes inhibited the growth of S.
      commune. It was observed that S. commune was capable of removing Acid Orange 7,
      Acid Red 18 and Reactive Black 5 with a maximum specific uptake capacity of
      44.23, 127.53 and 180.17 (mg/g) respectively for an initial concentration of 100
      mg/L of the dye. Higher decolorization was observed at lower concentrations for
      all the dyes. Finally it was found that the percentage decolorization was more in
      the case of Reactive Black 5 dye compared to the other two dyes used in the
      present investigation.

PMID- 16293416
TI  - Comparison of frontal plane trunk kinematics and hip and knee moments during
      anticipated and unanticipated walking and side step cutting tasks.
AB  - BACKGROUND: Frontal plane trunk and lower extremity adjustments during
      unanticipated tasks are hypothesized to influence hip and knee neuromuscular
      control, and therefore, contribute to anterior cruciate ligament (ACL) injury
      risk. The aims of this study were to examine frontal plane trunk/hip kinematics
      and hip and knee moments (measures of neuromuscular control) during unanticipated
      straight and side step cut tasks. METHODS: Kinematic and kinetic variables were
      collected while subjects performed two anticipated tasks, including walking
      straight (ST) and side step cutting (SS), and two unanticipated tasks (STU and
      SSU). Foot placement, thorax-pelvis-hip kinematic variables and hip and knee
      moments were calculated over the first 30% of stance. FINDINGS: Hip abduction
      angles and knee moments were significantly affected by task and anticipation. Hip
      abduction angles decreased, by 4.0-7.6 degrees , when comparing the SSU task to
      the ST, STU and SS tasks. The hip abduction angles were associated with foot
      placement and lateral trunk orientation. INTERPRETATION: Hip abduction angles and
      foot placement, not lateral trunk flexion influence trunk orientation.
      Anticipation influences hip and knee neuromuscular control and therefore may
      guide the development of ACL prevention strategies.

PMID- 16293415
TI  - Ankle ROM and stiffness measured at rest and during gait in individuals with and
      without diabetic sensory neuropathy.
AB  - INTRODUCTION: The purpose of our study was to examine the relationship between
      ankle dorsiflexion (DF) range of motion (ROM) and stiffness measured at rest
      (passively) and plantar loading during gait in individuals with and without
      diabetes mellitus (DM) and sensory neuropathy. Specifically, we sought to address
      three questions for this at-risk patient population: (1) Does peak passive DF ROM
      predict ankle DF ROM used during gait? (2) Does passive ankle stiffness predict
      ankle stiffness used during gait? (3) Are any of the passive or gait-related
      ankle measures associated with plantar loading? METHODS: Ten subjects with DM and
      10 age and gender matched non-diabetic control subjects participated in this
      study. Passive ankle DF ROM and stiffness were measured with the Iowa Ankle ROM
      device. Kinematic, kinetic and plantar pressure data were collected as subjects
      walked at 0.89 m/s. RESULTS: We found that subjects with DM have reduced passive
      ankle DF ROM and increased stiffness compared to non-diabetic control subjects,
      however, subjects with DM demonstrated ankle motion, stiffness and plantar
      pressures, similar to control subjects, while walking at the identical speed,
      0.89 m/s (2 mph). These data indicate that clinical measures of heel cord
      tightness and stiffness do not represent ankle motion or stiffness utilized
      during gait. Our findings suggest that subjects with DM utilize strategies such
      as shortening their stride length and reducing their push-off power to modulate
      plantar loading.

PMID- 16293418
TI  - Preparation of [61Cu]-2-acetylpyridine thiosemicarbazone complex as a possible
      PET tracer for malignancies.
AB  - Due to the interesting anti-proliferative properties of copper-thiosemicarbazone
      complexes, the production of a (61)Cu-labeled thiosemicarbazone, i.e. 2
      acetylpyridine thiosemicarbazone (APTS) was investigated. Copper-61 (T(1/2)=3.33
      h) was produced via the (64)Zn(p,alpha)(61)Cu nuclear reaction using a natural
      zinc target irradiated with 22 MeV protons for 500 microAh. The (61)Cu was
      separated from the irradiated target material by a two-step method and converted
      to acetate; this yielded a final activity of 222 GBq (6.0 Ci), with a
      radiochemical yield of >95%. The (61)Cu-acetate was mixed with 2-acetylpyridine
      thiosemicarbazone for 30 min at room temperature to yield [(61)Cu]APTS with a
      radiochemical yield of more than 80%. Colorimetric methods showed that residual
      chemical impurities in the product were below the accepted limits. Radio thin
      layer chromatography (RTLC) showed a radiochemical purity of more than 99% after
      C(18) column chromatography. A specific activity of about 370-740 MBq/mmol (10-20
      Ci/mmol) was obtained. The stability of the final product was checked in the
      absence and presence of human serum at 37 degrees C for up to 3 h. The partition
      coefficient of the final complex was also determined.

PMID- 16293417
TI  - Calibration of the Capintec CRC-712M dose calibrator for (18)F.
AB  - Primary standardisation was performed on a solution of (18)F using the 4pibeta
      gamma coincidence counting efficiency-tracing extrapolation method with (60)Co
      used as a tracer nuclide. The result was used to calibrate the ANSTO secondary
      standard ionisation chamber which is used to disseminate Australian activity
      standards for gamma emitters. Using the secondary activity standard for (18)F,
      the Capintec CRC-712M dose calibrator at the Australian National Medical
      Cyclotron (NMC) Positron Emission Tomography (PET) Quality Control (QC) Section
      was calibrated. The dial setting number recommended by the manufacturer for the
      measurement of the activity of (18)F is 439. In this work, the dial setting
      numbers for the activity measurement of the solution of (18)F in Wheaton vials
      were experimentally determined to be 443+/-12, 446+/-12, 459+/-11, 473+/-15 for
      0.1, 1, 4.5 and 9ml solution volumes, respectively. The uncertainties given above
      are expanded uncertainties (k=2) giving an estimated level of confidence of 95%.
      The activities determined using the manufacturer recommended setting number 439
      are 0.8%, 1.4%, 4.0% and 6.5% higher than the standardised activities,
      respectively. It is recommended that a single dial setting number of 459
      determined for 4.5ml is used for 0.1-9ml solution in Wheaton vials in order to
      simplify the operation procedure. With this setting the expended uncertainty
      (k=2) in the activity readout from the Capintec dose calibrator would be less
      than 6.2%.

PMID- 16293419
TI  - Synthesis and evaluation of ether containing 99mTc-nitrido dithiocarbamate
      complexes as brain perfusion imaging agent.
AB  - In the present study, a series of (99m)Tc-nitrido dithiocarbamate complexes
      containing ether linkages have been prepared and their brain perfusion
      characteristics studied. Two primary dithiocarbamates and two secondary
      dithiocarbamates were synthesized in >80% yield and were characterized by
      elemental analyses. The ligands were then labeled using a (99m)Tc-nitrido
      intermediate, prepared from sodium pertechnetate using commercially available
      nitrido kit-vials, at a low ligand concentration of 0.1 mg. The prepared
      complexes were obtained in more than 95% yield and were characterized by paper
      electrophoresis and HPLC. All the complexes were found to be neutral and eluted
      out as a single species in HPLC. Biodistribution studies were carried out in
      normal Swiss mice. All the complexes showed uptake in the brain. (99m)TcN
      complexes of secondary dithiocarbamates showed higher initial brain uptake (5 min
      p.i.) than their primary amine counterparts. However, all the complexes exhibited
      rapid washout from the brain.

PMID- 16293420
TI  - Cellular activities during a mixed leucocyte reaction in the teleost sea bass
      Dicentrarchus labrax.
AB  - In this investigation a number of "in vitro" activities of sea bass peripheral
      blood leucocytes (PBL) against allogeneic PBL inactivated by irradiation were
      studied. Stimulator PBL were cultured with inactivated allogeneic PBL, and direct
      counting of lymphocytes was done after 2 weeks by immunofluorescence and flow
      cytometry using mAbs DLT15 and DLIg3 specific for T-cells and B-cells,
      respectively. In a one-way mixed leucocyte reaction (MLR), results showed an
      increase of T lymphocytes, whereas B lymphocytes had values similar to those in
      control PBL. The increase of T-cells in MLR cultures was also confirmed using RT
      PCR by analyzing the expression of the T-cell receptor (beta-subunit) mRNA. The
      addition of 5 microg/ml of cyclosporin A (CsA) to the MLR caused a significant
      decrease in T-cell proliferation. Leucocytes from MLR cultures displayed an
      enhanced cytotoxic activity against xenogeneic target cells with respect to
      control PBL, raising the possibility of the presence of cytotoxic-like T
      lymphocytes. Cellular activation of PBL was confirmed in 2 weeks MLR by measuring
      antibody-induced intracellular Ca(++) mobilization with Fura-2 AM. This work
      represents the first direct quantitative determination of an "in vitro" T-cell
      activity in a teleost species.

PMID- 16293421
TI  - Vitellogenin is a novel player in defense reactions.
AB  - The significance of the presence of vitellogenin (Vg), a female-specific protein,
      in male and juvenile fish is uncertain. Here we show that the Vg purified from
      the rosy barb Puntius conchonius possesses both antibacterial and
      hemagglutinating activities in vitro, and the male fish challenged with
      Escherichia coli synthesize Vg. These suggest that in addition to being involved
      in yolk protein formation, Vg is also involved in defense reactions, a novel
      function assigned to Vg.

PMID- 16293422
TI  - The immunomodulatory effects of tuftsin on the non-specific immune system of
      Indian Major carp, Labeo rohita.
AB  - The purpose of this study was to determine if injections of different dosages of
      tuftsin would enhance the immune response and disease resistance against the
      infections due to the opportunistic pathogens Aeromonas hydrophila and
      Edwardsiella tarda in Labeo rohita fingerlings. Hence, four different dosages of
      tuftsin in PBS suspension at the rate of 0, 5, 10, 15 mg kg(-1) body weight of
      fish were injected intraperitoneally to the fingerlings of L. rohita at 2-week
      intervals for four times. After every 2-week interval, different serum
      biochemical, haematological and immunological parameters of fish were evaluated.
      Biochemical and haematological parameters including serum total protein content,
      albumin content, globulin content, albulin:globulin ratio, glucose content,
      leucocyte counts etc.; cellular immune parameters including superoxide anion
      production, phagocytic activities, lymphokine production index etc.; humoral
      immune parameters including lysozyme activity, complement activity, serum
      bactericidal activity etc., in the fish were evaluated after every 2-week
      interval. After 56 days, fish were divided into two subgroups under each major
      treatment group for challenge with two pathogens A. hydrophila and E. tarda. The
      mortality (%) and agglutinating antibody titre was recorded on 28th day post
      challenge. Most of the immune parameters including leucocyte count, phagocytic
      ratio, phagocytic index, lysozyme activity, complement activity, and serum
      bactericidal activity were significantly (p<or=0.05) maximum on 42 days after
      three i.p. injections of 10 mg kg(-1) body weight of tuftsin. Challenge study
      indicated least mortality in the group of fish injected with 10 mg kg(-1) body
      weight of tuftsin for four times. Multiple injections of tuftsin might have
      maintained the activation of phagocytic cells for a long period, which in turn
      led to long-term protection in the fish. Thus, multiple injections of 10 mg kg(
      1) body weight of tuftsin for three times can be advocated for enhancing the
      immune response of fish species under aquaculture.

PMID- 16293424
TI  - Comparison of the evolutionary distances among syngens and sibling species of
      Paramecium.
AB  - The morphospecies of the genus Paramecium have several mating type groups, so
      called syngens, composed of cells of complementary mating types. The Paramecium
      aurelia complex is composed of 15 sibling species assigned to the species from
      the syngen. To increase our understanding of the evolutionary relationships among
      syngen and sibling species of the genus Paramecium, we investigated the gene
      sequences of cytosol-type hsp70 from 7 syngens of Paramecium caudatum and 15
      sibling species of P. aurelia. Molecular phylogenetic trees indicated that the P.
      aurelia complex could be divided into four lineages and separated into each
      sibling species. However, we did not find any obvious genetic distance among
      syngens of P. caudatum, and they could only be separated into two closely related
      groups. These results indicated that the concept of syngens in P. caudatum
      differs quite markedly from that of the P. aurelia complex. In addition, we also
      discuss the relationships among these species and other species, Paramecium
      jenningsi and Paramecium multimicronucleatum, which were once classified as
      varieties of P. aurelia.

PMID- 16293425
TI  - Testing morphologically based phylogenetic theories within the cartilaginous
      fishes with molecular data, with special reference to the catshark family
      (Chondrichthyes; Scyliorhinidae) and the interrelationships within them.
AB  - A molecular phylogenetic investigation was conducted to examine phylogenetic
      relationships between various members of the catsharks (Chondrichthyes;
      Carcharhiniformes; Scyliorhinidae), and is the largest chondrichthyan data set
      yet analysed, consisting of nearly 130,000 nucleotides. Three mitochondrial DNA
      genes were used to construct the phylogenies, cytochrome b, NADH-2, and NADH-4,
      with 41 sequences from 18 taxa being novel. These sequences were either used
      separately or combined into a single data set, and phylogenies were constructed
      using various methods, however, only the Bayesian inference tree derived from the
      cytochrome b data set was resolved sufficiently for phylogenetic inferences to be
      made. Interestingly, the family Scyliorhinidae was not supported by the results
      and was found to be paraphyletic. The Scyliorhininae and Pentanchinae were
      supported, whereas the Pentanchini clade was present, but not well supported. The
      Halaelurini hypothesis was supported with Holohalaelurus identified as the basal
      genus of that clade, and Haploblepharus edwardsii identified as the basal taxon
      for that genus. Elsewhere within the Chondrichthyes, the Carcharhiniformes and
      the Lamniformes were found to be monophyletic, and the Heterodontiformes was
      placed within the Squalimorphs. The placement of the skates and rays in these
      analyses support the Batoidea as being sister to the Elasmobranchii.

PMID- 16293423
TI  - Phylogeny of the Cucurbitales based on DNA sequences of nine loci from three
      genomes: implications for morphological and sexual system evolution.
AB  - The Cucurbitales are a clade of rosids with a worldwide distribution and a
      striking heterogeneity in species diversity among its seven family members: the
      Anisophylleaceae (29-40 species), Begoniaceae (1400 spp.), Coriariaceae (15
      spp.), Corynocarpaceae (6 spp.), Cucurbitaceae (800 spp.), Datiscaceae (2 spp.),
      and Tetramelaceae (2 spp.). Most Cucurbitales have unisexual flowers, and species
      are monoecious, dioecious, andromonoecious, or androdioecious. To resolve
      interfamilial relationships within the order and to polarize morphological
      character evolution, especially of flower sexual systems, we sequenced nine
      plastids (atpB, matK, ndhF, rbcL, the trnL-F region, and the rpl20-rps12 spacer),
      nuclear (18S and 26S rDNA), and mitochondrial (nad1 b/c intron) genes (together
      approximately 12,000 bp) of 26 representatives of the seven families plus eight
      outgroup taxa from six other orders of the Eurosids I. Cucurbitales are strongly
      supported as monophyletic and are closest to Fagales, albeit with moderate
      support; both together are sister to Rosales. The deepest split in the
      Cucurbitales is that between the Anisophylleaceae and the remaining families;
      next is a clade of Corynocarpaceae and Coriariaceae, followed by Cucurbitaceae,
      which are sister to a clade of Begoniaceae, Datiscaceae, and Tetramelaceae. Based
      on this topology, stipulate leaves, inferior ovaries, parietal placentation, and
      one-seeded fruits are inferred as ancestral in Cucurbitales; exstipulate leaves,
      superior ovaries, apical placentation, and many-seeded fruits evolved within the
      order. Bisexual flowers are reconstructed as ancestral, but dioecy appears to
      have evolved already in the common ancestor of Begoniaceae, Cucurbitaceae,
      Datiscaceae, and Tetramelaceae, and then to have been lost repeatedly in
      Begoniaceae and Cucurbitaceae. Both instances of androdioecy (Datisca glomerata
      and Schizopepon bryoniifolius) evolved from dioecious ancestors, corroborating
      recent hypotheses about androdioecy often evolving from dioecy.

PMID- 16293426
TI  - Functional outcome of distal bypasses for lower limb ischemia.
AB  - OBJECTIVES: The purpose of this study was to assess limb salvage and functional
      outcome in patients who underwent distal reconstructions. DESIGN: Retrospective
      study. MATERIALS AND METHODS: Fifty-nine consecutive patients underwent 63
      femorodistal bypass operations during 1998-2002 at a university hospital. Late
      functional outcome was assessed using a questionnaire (mean 27 months after the
      primary operation). RESULTS: At the end of the study, 81% (30/37) of the
      surviving patients were alive with a viable limb. In all, 90% (27/30) of patients
      were living in their own homes and 3% (1/30) in a nursing home. Sixty percent
      (18/30) were able to walk independently. The walking distance was unlimited in
      42% (13/31) and limited in 42% (13/31) of the operated limbs. In 16% (5/31) of
      cases, the treated limbs served only as a support. CONCLUSIONS: According to our
      results, the functional outcome of distal bypasses seems to be favourable. It is
      recommended that these operations should be performed even in elderly patients to
      avoid major amputations and to maintain the independence of the patient.

PMID- 16293427
TI  - Stroke risk in females: The ACSRS Study.

PMID- 16293428
TI  - Growth rate and associated factors in small abdominal aortic aneurysms.
AB  - OBJECTIVE: To study the growth rate and factors influencing progression of small
      infrarenal abdominal aortic aneurysms (AAA). DESIGN: Observational, longitudinal,
      prospective study. PATIENTS AND METHODS: We followed patients with AAA <5 cm in
      diameter in two groups. Group I (AAA 3-3.9 cm, n = 246) underwent annual
      ultrasound scans. Group II (AAA 4-4.9 cm, n = 106) underwent 6-monthly CT scans.
      RESULTS: We included 352 patients (333 men and 19 women) followed for a mean of
      55.2+/-37.4 months (6.3-199.8). The mean growth rate was significantly greater in
      group II (4.72+/-5.93 vs. 2.07+/-3.23 mm/year; p<0.0001). Group II had a greater
      percentage of patients with rapid aneurysm expansion (>4 mm/year) (36.8 vs.
      13.8%; p<0.0001). The classical cardiovascular risk factors did not influence the
      AAA growth rate in group I. Chronic limb ischemia was associated with slower
      expansion (< or = 4 mm/year) (OR 0.47; CI 95% 0.22-0.99; p = 0.045). Diabetic
      patients in group II had a significantly smaller mean AAA growth rate than non
      diabetics (1.69+/-3.51 vs. 5.22+/-6.11 mm/year; p = 0.032). CONCLUSIONS: The
      expansion rate of small AAA increases with the AAA size. AAA with a diameter of 3
      3.9 cm expand slowly, and they are very unlikely to require surgical repair in 5
      years. Many 4-4.9 cm AAA can be expected to reach a surgical size in the first 2
      years of follow-up. Chronic limb ischemia and diabetes are associated with
      reduced aneurysm growth rates.

PMID- 16293429
TI  - Nitric oxide stimulates the erythrocyte for ascorbate recycling.
AB  - S-Nitrosothiols act as carrier and reservoir of nitric oxide (NO), and release NO
      under stimulation of ascorbate (Asc). Erythrocyte can regenerate Asc from its
      oxidised products, thus saving this powerful antioxidant. In this paper the
      effect of donors of NO, superoxide, and peroxynitrite (SpNONOate, KO(2), and SIN
      1, respectively) on the erythrocyte production of Asc was investigated. We report
      here that NO stimulated, while superoxide and peroxynitrite decreased, the Asc
      recycling. The NO-stimulating effect on the erythrocyte production of Asc was
      confirmed by using GSNO, a natural occurring S-nitrosothiol, as NO donor. These
      data highlight a new property of NO, that is the stimulation of erythrocytes for
      their Asc recycling. Such a property might contribute to regenerate Asc from its
      oxidised forms, thus preventing its depletion in the circulation. Temperature and
      pH significantly affected, both in absence and presence of NO, the recycling of
      Asc by erythrocytes. We propose that a positive feedback, involving the
      reciprocal stimulation between Asc and S-nitrosothiols, might enhance productions
      of Asc by erythrocytes and NO release by circulating S-nitrosothiols.

PMID- 16293430
TI  - Linear interaction energy models for beta-secretase (BACE) inhibitors: Role of
      van der Waals, electrostatic, and continuum-solvation terms.
AB  - Computing the binding affinity of a protein-ligand complex is one of the most
      fundamental and difficult tasks in computer-aided drug design. Many approaches
      for computing binding affinities can be classified as linear interaction energy
      (LIE) models as they rely on some type of linear fit of computed interaction
      energies between ligand and protein. We have examined the computed interaction
      energies of a series of beta-secretase (BACE) inhibitors in terms of van der
      Waals, coulombic, and continuum-solvation contributions to ligand binding. We
      have also systematically examined the effect of different protonation states of
      the protein and ligands. We find that the binding affinities are relatively
      insensitive to the protonation state of the protein when neutral ligands are
      considered. Inclusion of charged ligands leads to large deviations in the
      coulomb, solvation, and even van der Waals terms. The latter is due to increased
      repulsive van der Waals interactions in the complex due to the strong coulomb
      attraction found between oppositely charged functional groups in the protein and
      ligand. In general, we find that the best models are obtained when the protein is
      judiciously charged (e.g. Asp32-, Arg235+) and the potentially charged ligands
      are treated as neutral.

PMID- 16293432
TI  - An acetylated 120-kDa lysosomal transmembrane protein is absent from
      mucopolysaccharidosis IIIC fibroblasts: a candidate molecule for MPS IIIC.
AB  - Genetic deficiency of the lysosomal enzyme, acetyl-CoA: alpha-glucosaminide N
      acetyltransferase (N-acetyltransferase), which catalyses the transmembrane
      acetylation of heparan sulfate results in severe neurodegenerative disease,
      mucopolysaccharidosis IIIC. N-Acetyltransferase has never been characterized
      structurally and its gene has never been identified. We combined traditional
      methods of enzyme purification with organellar proteomics, isolating lysosomal
      membranes from mouse liver using differential centrifugation and osmolysis,
      followed by detergent extraction and purification of N-acetyltransferase by
      liquid chromatography. Partially purified enzyme had a molecular mass of 240 kDa
      and pI of 7.4 by gel filtration and chromatofocusing. Its specific activity
      varied with protein concentration typical of oligomeric enzymes or multienzyme
      complexes. Incubation of N-acetyltransferase with acetyl[14C]CoA in the absence
      of the acceptor of the acetyl group resulted in radioactive labeling of a 120-kDa
      polypeptide, suggesting that it represents a subunit containing the enzyme active
      site. Furthermore, following acetyl[14C]-labeling, the 120-kDa protein was
      present in the lysosomal membranes purified from the normal human skin
      fibroblasts but absent in those from the skin fibroblasts of MPS IIIC patients.

PMID- 16293431
TI  - A mutation on exon 6 of guanidinoacetate methyltransferase (GAMT) gene supports a
      different function for isoform a and b of GAMT enzyme.
AB  - A new patient affected by Guanidinoacetate methyltransferase (GAMT) deficiency
      was reported. This 13-year-old girl presented with mental retardation, as main
      symptom, associated with a typical pattern of biochemical and neurochemical
      (brain magnetic resonance spectroscopy) alterations. Molecular study detected a
      L197P transition on exon 6 of the GAMT gene. Since this mutation leaves the
      isoform B of the GAMT enzyme unaffected, the occurrence of biochemical
      alterations and disease in this subject testifies against the possibility that
      isoform b had GAMT activity.

PMID- 16293433
TI  - First detection of Anaplasma phagocytophilum in quill mites (Acari:
      Syringophilidae) parasitizing passerine birds.
AB  - Forest passerine birds and their ectoparasites: Ixodes ricinus ticks and
      Syringophilidae quill mites were surveyed for infection with Anaplasma
      phagocytophilum in west-central Poland. Of 126 birds captured from May to June of
      2002, 71 (56.3%) comprising eight species, hosted immature I. ricinus ticks. A
      total of 383 ticks and 71 blood samples collected from tick-infested birds were
      investigated by PCR. The pathogen was not detected in either bird-derived ticks
      or in blood samples. Among the captured birds, a total of 14 individuals
      representing four species hosted quill mites from the family Syringophilidae.
      Three of the 14 mite pools recovered from the 14 mite-infested birds harbored A.
      phagocytophilum DNA by amplifying both the epank1 and p44 gene. The PCR-positive
      pools originated from one blackbird and two starlings. The specific biology of
      syringophilid mites, which parasitize exclusively inside the quill of feathers,
      feeding on host subcutaneous fluids, implies that they must have acquired the
      pathogen from a bacteremic bird. These results provide the first indirect
      evidence that at least some passerine hosts are prone to develop systemic
      infection with A. phagocytophilum under natural conditions. Consequently, the
      infected quill mites may serve as a "biological marker" of past or current
      infection with the agent within birds.

PMID- 16293434
TI  - Implications of oxidative stress in the cytotoxicity of Pseudomonas aeruginosa
      ExoU.
AB  - ExoU PLA2-like activity has been shown to account for membrane lysis and acute
      death of infected cells. Translocation of effector proteins by the type III
      secretion systems depends on close contact between microbial and host cells. Our
      finding that both the ExoU-producing PA103 Pseudomonas aeruginosa and its mutant
      obtained by deletion of exoU adhered poorly to endothelial cells (EC) led to the
      hypothesis that, in some cells, the amount of injected toxin may not be enough to
      induce cell lysis but cells would suffer from a long-term effect of ExoU
      intoxication. To address this question, cells were exposed to both bacteria for 1
      h and then treated with gentamicin-containing medium, to eliminate infecting
      microorganisms. After 24 h, the percentage of viable EC in PA103-infected
      cultures was significantly lower than in cultures exposed to the mutant, as
      determined by the MTT assay. Cell death was not likely to depend on the ExoU
      lytic activity since cell labeling with propidium iodide was similar in cultures
      infected with both bacterial strains. Bacterial cytotoxicity was significantly
      reduced by MAFP, a specific inhibitor of cPLA2 and iPLA2. Since the PLA2 activity
      on membrane phospholipids generates free fatty acid, including arachidonic acid
      (AA), we next compared the bacterial ability to release AA from infected EC.
      PA103 was shown to induce a potent AA release that was inhibited by MAFP. AA
      oxidation by oxygenases generates eicosanoids, known to induce both cell death
      and proliferation. However neither inhibitors of cyclooxygenases (ibuprofen) nor
      lipoxygenases (NDGA) reduced the ExoU toxicity. Since non-enzymatic oxidation of
      AA generates reactive radicals, we next investigated the PA103 ability to induce
      oxidative stress in infected cells. FACS analysis of cell labeling with the C-11
      fluor probe and with anti-4-hydroxynonel antibody revealed a significant
      peroxidation of cell membrane lipids. These results, together with our finding
      that PA103-infected EC death was significantly attenuated by alpha-tocopherol,
      led to the conclusion that AA-induced oxidative stress may be another mechanism
      of cell damage in the course of infection by ExoU-producing P. aeruginosa.

PMID- 16293435
TI  - Gastrointestinal nematode infection is associated with variation in innate immune
      responsiveness.
AB  - Ex vivo monocyte cytokine responses (IL-1beta, TNF-alpha, IL-12p70, IL-10, TGF
      beta) to bacterial TLR2 and TLR4 ligands were quantified in 47 gastrointestinal
      (GI) nematode-exposed children in Pemba Island, Tanzania. Worminess (estimated by
      faecal egg counts (FEC)) had a positive relationship with pro-inflammatory TNF
      alpha and IL-1beta responsiveness to the TLR ligands. In particular, there was a
      strong significant relationship with TNF-alpha response to TLR4 ligand (LPS).
      There were no significant associations between regulatory responses (IL-10, TGF
      beta) and worminess. These results are consistent with the possibility that GI
      nematodes modulate innate responses and may indicate a potential mechanism for
      interactions between GI nematodiasis and important bystander pathogens.

PMID- 16293436
TI  - Glucuronoxylomannan-mediated interaction of Cryptococcus neoformans with human
      alveolar cells results in fungal internalization and host cell damage.
AB  - Infection by Cryptococcus neoformans begins with inhalation of infectious
      propagules. Fungi reach the lung tissue and interact with epithelial cells in a
      crucial but poorly understood process. In this study, the interaction of C.
      neoformans with the human alveolar epithelial cell lineage A549 was investigated,
      focusing on the relevance of the capsular polysaccharide in this process. The
      association of encapsulated strains with A549 cells was significantly inhibited
      by a monoclonal antibody to glucuronoxylomannan (GXM), a major component of the
      cryptococcal capsule. A purified preparation of GXM produced similar results,
      suggesting the occurrence of surface receptors for this polysaccharide on the
      surface of alveolar cells. A549 cells were in fact able to bind soluble GXM, as
      confirmed by indirect immunofluorescence analysis using the anti-polysaccharide
      antibody. C. neoformans is internalized after GXM-mediated interaction with A549
      cells in a process that culminates with death of host cells. Our results suggest
      that C. neoformans can use GXM for attachment to alveolar epithelia, allowing the
      fungus to reach the intracellular environment and damage host cells through still
      uncharacterized mechanisms.

PMID- 16293437
TI  - Dehydroepiandrosterone decreases while cortisol increases in vitro growth and
      viability of Entamoeba histolytica.
AB  - In vitro exposure of Entamoeba histolytica trophozoites to the sex steroids
      17beta-estradiol, progesterone, and dehydrotestosterone had little effect on
      parasite viability or proliferation. However, treatment with the adrenal steroid
      dehydroepiandrosterone (DHEA) markedly inhibited parasite proliferation,
      adherence and motility, and at a certain dose it induced trophozoite lysis. The
      opposite effect on proliferation was found when the trophozoites were exposed to
      cortisol. Moreover, DHEA decreased while cortisol increased the parasite's DNA
      synthesis determined by 3H-thymidine incorporation. Trophozoite lysis by DHEA
      appeared to be caused by a necrotic rather than an apoptotic process, as observed
      in propidium iodide and terminal deoxynucleotidyl transferase-mediated
      biotinylated UTP nick end labeling assays. A possible mechanisms of action was
      derived from experiments demonstrating that the activity of a putative 3-hydroxy
      3-methyl glutaryl CoA reductase detected in trophozoite extracts was inhibited in
      the presence of DHEA. Contrary to its in vitro inhibitory effect, in vivo
      administration of DHEA to infected hamsters resulted in exacerbation of the
      amebic liver abscesses. These results demonstrated that androgen steroids act
      directly upon E. histolytica growth and viability, and may shed new light on some
      age and gender differences in disease progression, as well as finding application
      in the drug treatment of human amebiasis.

PMID- 16293439
TI  - A concentrated parameter model for the human cardiovascular system including
      heart valve dynamics and atrioventricular interaction.
AB  - Numerical modeling of the human cardiovascular system has always been an active
      research direction since the 19th century. In the past, various simulation models
      of different complexities were proposed for different research purposes. In this
      paper, an improved numerical model to study the dynamic function of the human
      circulation system is proposed. In the development of the mathematical model, the
      heart chambers are described with a variable elastance model. The systemic and
      pulmonary loops are described based on the resistance-compliance-inertia concept
      by considering local effects of flow friction, elasticity of blood vessels and
      inertia of blood in different segments of the blood vessels. As an advancement
      from previous models, heart valve dynamics and atrioventricular interaction,
      including atrial contraction and motion of the annulus fibrosus, are specifically
      modeled. With these improvements the developed model can predict several
      important features that were missing in previous numerical models, including
      regurgitant flow on heart valve closure, the value of E/A velocity ratio in
      mitral flow, the motion of the annulus fibrosus (called the KG diaphragm pumping
      action), etc. These features have important clinical meaning and their changes
      are often related to cardiovascular diseases. Successful simulation of these
      features enhances the accuracy of simulations of cardiovascular dynamics, and
      helps in clinical studies of cardiac function.

PMID- 16293438
TI  - Stimulation, inhibition and death of macrophages infected with Trichophyton
      rubrum.
AB  - Trichophyton rubrum is the most common pathogen causing dermatophytosis,
      accounting for approximately 80% of the reported cases of onychomycosis. Since
      90% of the chronic dermatophyte infections are caused by T. rubrum, it is likely
      that this pathogen must have evolved mechanisms that evade or suppress cell
      mediated immunity. Several reports have highlighted the participation of
      phagocytes in the immune defense against fungi; however, few studies have
      addressed the role of these cells in dermatophytosis. In this study, we
      investigated the interactions of resident and peritoneal macrophages with T.
      rubrum. We show here that the interaction of T. rubrum conidia with resident
      macrophages results in the production of TNF-alpha and IL-10 but not IL-12 and
      nitric oxide. Infected macrophages down-regulated the expression of co
      stimulatory molecules (CD80 and CD54). We also show that phagocytosis of T.
      rubrum conidia is inhibited by the addition of fungal exoantigens or mannan.
      Cytotoxicity assays indicated that after 8 h of conidia ingestion macrophage
      viability decreased drastically. Electron microscopy revealed that the ingested
      conidia grow and differentiate into hyphae inside macrophages leading to rupture
      of the macrophage membrane.

PMID- 16293440
TI  - IgA1 protease.
AB  - IgA1 proteases are proteolytic enzymes that cleave specific peptide bonds in the
      human immunoglobulin A1 (IgA1) hinge region sequence. Several species of
      pathogenic bacteria secrete IgA1 proteases at mucosal sites of infection to
      destroy the structure and function of human IgA1 thereby eliminating an important
      aspect of host defence. IgA1 proteases are known as autotransporter proteins as
      their gene structure encodes the information to direct their own secretion out of
      the bacterial cell. The iga gene structure is also thought to contribute to the
      antigenic heterogeneity demonstrated by the IgA1 proteases during infections and
      the cleavage specificity of the IgA1 proteases for human IgA1. The IgA1 proteases
      have therefore been implicated as important virulence factors that contribute to
      bacterial infection and colonisation. The development of strategies to inactivate
      these IgA1 proteases has become the subject of recent research, as this has the
      potential to reduce bacterial colonisation at mucosal surfaces.

PMID- 16293441
TI  - A computer-aided diagnosis system for detection of lung nodules in chest
      radiographs with an evaluation on a public database.
AB  - A computer algorithm for nodule detection in chest radiographs is presented. The
      algorithm consists of four main steps: (i) image preprocessing; (ii) nodule
      candidate detection; (iii) feature extraction; (iv) candidate classification. Two
      optional extensions to this scheme are tested: candidate selection and candidate
      segmentation. The output of step (ii) is a list of circles, which can be
      transformed into more detailed contours by the extra candidate segmentation step.
      In addition, the candidate selection step (which is a classification step using a
      small number of features) can be used to reduce the list of nodule candidates
      before step (iii). The algorithm uses multi-scale techniques in several stages of
      the scheme: Candidates are found by looking for local intensity maxima in
      Gaussian scale space; nodule boundaries are detected by tracing edge points found
      at large scales down to pixel scale; some of the features used for classification
      are taken from a multi-scale Gaussian filterbank. Experiments with this scheme
      (with and without the segmentation and selection steps) are carried out on a
      previously characterized, publicly available database, that contains a large
      number of very subtle nodules. For this database, counting as detections only
      those nodules that were indicated with a confidence level of 50% or more,
      radiologists previously detected 70% of the nodules. For our algorithm, it turns
      out that the selection step does have an added value for the system, while
      segmentation does not lead to a clear improvement. With the scheme with the best
      performance, accepting on average two false positives per image results in the
      identification of 51% of all nodules. For four false positives, this increases to
      67%. This is close to the previously reported 70% detection rate of the
      radiologists.

PMID- 16293442
TI  - Early immune-mediated response to ribavirin combined with IFN in patients with
      chronic hepatitis C.
AB  - AIM: This study was to investigate the immunomodulatory effects of ribavirin
      combined with interferon (IFN)-alpha 2b (R+IFN) compared with consensus IFN
      monotherapy (IFN-Con) in chronic hepatitis C (CHC) patients. PATIENTS AND
      METHODS: Thirty-four adult patients with biopsy-proven CHC, who were infected
      with HCV genotype 2a or 2b, were studied. A 24-week regimen of IFN-alpha 2b (6MU
      daily for 2 weeks followed by 6MU tiw for 22 weeks) and ribavirin (600-800mg/day
      for 24 weeks) was given to 17 patients. The other 17 patients were treated with a
      24-week regimen of IFN-Con (18MU daily for 2 weeks followed by 18MU tiw for 22
      weeks). Flow cytometric determination of cytoplasmic IFN-gamma and IL-4
      expression in peripheral blood CD4+ T cells was performed, and the percentage of
      IFN-gamma+ and IL-4- (Th1), IFN-gamma- and IL-4+ (Th2) cells were calculated
      before and 3, 7, 14, and 28 days after the start of therapy. RESULTS: In the
      R+IFN group, the percentage of Th1 cell peaked on day 3, and then decreased to
      near baseline by day 14, while the percentage of Th2 cell did not change. In the
      IFN-Con group, the percentage of Th1 cell peaked on day 14 and the percentage of
      Th2 cell peaked on day 3, and then decreased to near baseline by day 14.
      CONCLUSIONS: Our results suggest that ribavirin induces an early immune response
      by peripheral blood CD4+ T cells in CHC patients.

PMID- 16293443
TI  - Development of a rapid semi-quantitative immunochromatographic assay for serum
      hepatocyte growth factor and its usefulness in acute liver failure.
AB  - Measurement of serum human hepatocyte growth factor (HGF) by enzyme-linked
      immunosorbent assay (ELISA) is useful for the early diagnosis and prediction of
      prognosis of patients with acute liver failure (ALF). This ELISA methodology,
      however, is neither rapid nor convenient for use at the bedside. In this study,
      we have developed a rapid semi-quantitative immunochromatographic (IC) assay and
      evaluated its usefulness in assessing patients with acute hepatic injury. Only
      100mul of serum is required; the assay can be easily completed in 20min. The
      values obtained using this novel assay correlated well with the values obtained
      using the standard ELISA protocol. In addition, the values obtained in the IC
      assay correlated with clinical course; increased serum HGF levels were associated
      with an increased frequency of ALF and death. These results indicate that this
      rapid semi-quantitative IC assay for HGF is useful for the early diagnosis of ALF
      and prediction of clinical outcome in acute hepatic injury.

PMID- 16293444
TI  - From concepts to clinical reality: an essay on the benchmarking of biomedical
      terminologies.
AB  - It is only by fixing on agreed meanings of terms in biomedical terminologies that
      we will be in a position to achieve that accumulation and integration of
      knowledge that is indispensable to progress at the frontiers of biomedicine.
      Standardly, the goal of fixing meanings is seen as being realized through the
      alignment of terms on what are called 'concepts.' Part I addresses three versions
      of the concept-based approach--by Cimino, by Wuster, and by Campbell and
      associates--and surveys some of the problems to which they give rise, all of
      which have to do with a failure to anchor the terms in terminologies to
      corresponding referents in reality. Part II outlines a new, realist solution to
      this anchorage problem, which sees terminology construction as being motivated by
      the goal of alignment not on concepts but on the universals (kinds, types) in
      reality and thereby also on the corresponding instances (individuals, tokens). We
      outline the realist approach and show how on its basis we can provide a benchmark
      of correctness for terminologies which will at the same time allow a new type of
      integration of terminologies and electronic health records. We conclude by
      outlining ways in which the framework thus defined might be exploited for
      purposes of diagnostic decision-support.

PMID- 16293445
TI  - Wavelet transform shows age-related changes of heart rate variability within
      independent frequency components.
AB  - Reduction in overall heart rate variability (HRV) associated with aging is
      determined by a decreased amplitude of heart rate oscillations at all frequency
      levels, including high frequency (HF) oscillations attributed to respiratory
      sinus arrhythmia, low frequency (LF) oscillations attributed to Meyer waves and
      very low frequency (VLF) oscillations of an uncertain origin, presumably linked
      among others to thermoregulation. However, no studies were conducted to determine
      whether heart rate oscillations at independent frequency levels show themselves
      reduced HRV. Wavelet transform was applied to filter specific frequency
      components of HRV in a sample of younger (21-34 years old) and older (68-85 years
      old) healthy subjects. HRV indexes were measured within HF, LF and VLF
      components. The standard deviation of all RR intervals (SDNN) and the square root
      of the mean squared differences of successive RR intervals (RMSSD) were used as
      conventional linear time-domain measures. Sample entropy (SampEn) was used as a
      measure of nonlinear variability. Aged subjects showed lower SDNN at VLF (p <
      0.001), LF (p = 0.007) and HF (p < 0.001). Lower RMSSD was observed in older
      people at VLF (p < 0.001), LF (p = 0.005) and HF (p < 0.001). SampEn was reduced
      by aging only at VLF level (p < 0.001). In aged people, linear variability was
      diminished within all frequency components, while nonlinear variability was lower
      only at VLF level. Preserved central, nonreflex autonomic modulation over the
      baroreflex control and the central cardiopulmonary coupling might explain this
      observation. Potential applications of this method include the study of heart
      rate regulation during sleep in which a complex interaction between the
      sympathetic and the parasympathetic activity takes place.

PMID- 16293446
TI  - Saccharomyces cerevisiae Ogg1 prevents poly(GT) tract instability in the
      mitochondrial genome.
AB  - Reactive oxygen species can attack the mitochondrial genome to produce a vast
      array of oxidative DNA lesions including 8-oxo-7,8-dihydro-2'-deoxyguanosine (8
      oxo-dGuo). We assess the role of the Saccharomyces cerevisiae 8-oxo-dGuo DNA
      glycosylase, Ogg1, in the maintenance of a poly(GT) tract reporter system present
      in the mitochondrial genome. Deletion in the poly(GT) tract causes the reporter
      system to produce arginine-independent (Arg+) colonies. We show that the
      mitochondrial form of Ogg1 is functionally active at processing 8-oxo-dGuo
      lesions and that Ogg1-deficient cells exhibit nearly six-fold elevated rate of
      Arg+ mutants under normal growth condition, as compared to the parent.
      Overexpression of Ogg1 completely suppressed the high rate of Arg+ mutations to
      levels lower than the parental, suggesting that Ogg1 function could be limited in
      the mitochondria. Further analysis revealed that the Arg+ mutations can be
      prevented if the cells are grown under anaerobic conditions. These findings
      provide in vivo evidence that oxidative stress induces the formation of lesions,
      most likely 8-oxo-dGuo, which must be repaired by Ogg1, otherwise the lesions can
      trigger poly(GT) tract instability in the mitochondrial genome. We also
      demonstrate that overproduction of the major apurinic/apyrimidinic (AP)
      endonuclease Apn1, a nuclear and mitochondrial enzyme with multiple DNA repair
      activities, substantially elevated the rate of Arg+ mutants, but which was
      counteracted by Ogg1 overexpression. We suggest that Ogg1 might bind to AP sites
      and protect this lesion from the spurious action of Apn1 overproduction. Thus,
      cleavage of AP site located within or in the vicinity of the poly(GT) tract could
      destabilize this repeat.

PMID- 16293447
TI  - Absence of FES exon 16 and 17 mutation in the colorectal carcinomas in Korean
      patients.

PMID- 16293448
TI  - Helicobacter pylori infection and serum gastrin, ghrelin and leptin in children
      of Polish shepherds.
AB  - OBJECTIVE: Family unit is generally accepted as one of the contributors to
      Helicobacter pylori infection that is most frequently acquired in childhood, so
      it seems logical to diagnose and treat this infection in childhood. This study
      was designed to assess H. pylori prevalence in children from shepherd families
      having contacts with sheep. MATERIAL AND METHODS: This study involved 146
      children (58 M/88 F, age 6-17 years; mean: 10.2 years) from families living in
      Polish Tatra Mountains with contact (group A, n=58) or without contact with sheep
      (group B, n=88). H. pylori status was determined by (13)C-urea breath test and
      was compared to 141 age- and gender-matched urban controls (group C). In both
      groups of mountain children, the anti-H. pylori and anti-CagA IgG were measured
      by ELISA and serum gastrin, ghrelin and leptin concentrations by RIA. RESULTS:
      The H. pylori prevalence in group A was significantly higher (58.6%) than that in
      group B (21.6%) and urban controls (26%). Serum gastrin concentrations were
      significantly higher in H. pylori-positive than in H. pylori-negative mountain
      children (52.2+/-5.8 pmol/L versus 22.7+/-2.1 pmol/L), while serum ghrelin and
      leptin concentrations were significantly lower in H. pylori-infected (741+/-112
      pg/mL and 3.6+/-0.8 ng/mL) than in non-infected children (1323+/-104 pg/mL and
      8.6+/-2.4 ng/mL). CONCLUSIONS: Children with sheep contact show about twice
      higher H. pylori prevalence and higher serum gastrin but lower ghrelin and leptin
      levels than those without H. pylori infection. Considering almost 100% positive
      13C-urea breath test in sheep, it is reasonable to propose that H. pylori
      infection in shepherd children may originate from sheep and the infection might,
      therefore, be considered as zoonosis.

PMID- 16293452
TI  - Critical look at the legalization of the liberal use of high-dose narcotics: is
      this a reality?

PMID- 16293454
TI  - Clinical outcome of surgical treatment of failed back surgery syndrome.
AB  - BACKGROUND: Failed back surgery syndrome (FBSS) is a condition in which there is
      failure to improve satisfactorily after back surgery. It is characterized by
      intractable pain and various degrees of functional disability after lumbar spine
      surgery. It is estimated that this complication occurs in 5% to 10% of patients
      after spinal surgeries. The major causes of FBSS are fibrosis and adhesions,
      spinal instability, recurrent herniated disk, and inadequate decompression. The
      purpose of this study is to report on the postsurgical outcome after a redo
      spinal surgery. METHODS: We prospectively studied 50 patients with FBSS. The
      underlying pathology was identified and all the patients were treated surgically.
      Redo surgery was targeted at correcting the underlying pathology: removal of
      recurrent or residual disk, release of adhesions with neural decompression, and
      fusion with or without instrumentation. The postsurgical outcome was studied
      using the Oswestry Disability Questionnaire (ODQ). RESULTS: The average
      preoperative ODQ mean score was 80.8; the average postoperative ODQ mean score
      was 36.6 at 1 month and 24.2 at 1 year. Best scores were obtained at 3 months of
      follow-up in most cases. Successful outcome (>50% pain relief) could be achieved
      in 92% of the patients at 1 year. CONCLUSION: The current study shows that
      successful management of patients with FBSS could be achieved with proper patient
      selection, correct preoperative diagnosis, and adequate surgical procedure
      targeting the underlying pathology.

PMID- 16293457
TI  - Costs of postoperative cerebrospinal fluid leakage: 1-year, retrospective
      analysis of 412 consecutive nontrauma cases.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) leaks are widely recognized as commonly
      occurring postoperative complications of neurosurgical procedures. We will focus
      on the direct costs associated with CSF leaks in a single center across multiple
      neurosurgical procedures, based on a retrospective analysis. We will also compare
      the costs of using a synthetic agent to prevent such leaks with these costs from
      a more recent study. METHODS: The single-center retrospective study was carried
      out at the Neurosurgical Center Nijmegen (University Medical Center St Radboud
      and Canisius Wilhelmina Hospital, Nijmegen, Netherlands) from January 01, 1999,
      until December 31, 1999. Four hundred twelve consecutive, nontrauma, elective
      procedures were examined. RESULTS: By applying strict criteria for CSF leakage
      (including those self-limiting subcutaneous minor CSF collection), we found an
      overall leak rate of 10.7% with a lower number for supratentorial and
      transsphenoidal procedures and much higher numbers for infratentorial procedures
      and extensive skull base procedures (6 [12.8%] of 47 and 18 [34.6%] of 52,
      respectively). The CSF leak in these 44 patients was associated with high
      additional costs which accounted for 21.7% of the total costs of all 412
      procedures or on average 1508 per patient and procedure. If DuraSeal (Confluent
      Surgical, Inc, Waltham, MA) were to be used prophylactically for every procedure,
      and assuming a 4% leak rate postprocedure (which was achieved in a more recent
      study of 46 patients using DuraSeal), there would be a saving of 550 for every
      procedure (reduction in additional costs of CSF leak minus the cost of the
      sealant), or a total saving of 226600 in the series of 412 patients. CONCLUSION:
      Our analysis establishes that CSF leaks occur with high frequency and incur
      significant costs across all types of surgical procedures. A direct correlation
      of this complication (and ensuring costs) is observed with more extensive
      procedures, and reduction of these significant costs can be achieved by using
      augmentation of the dural closure with DuraSeal.

PMID- 16293460
TI  - Management of patients with cavernous angiomas presenting epileptic seizures.
AB  - BACKGROUND: The aim of this study was to establish a treatment strategy for
      patients with cavernous angiomas and have seizures. METHODS: We analyzed
      retrospectively 31 patients with cavernous angiomas presenting with seizures. Of
      the 31 patients, 15 (11 men, 4 women) had been treated medically (the medical
      group) and 16 (11 men, 5 women) had been treated surgically (the surgical group).
      The percentage of patients who became seizure-free and the number of
      anticonvulsants used were compared between these 2 groups. The mean follow-up
      period was 5.3 years (range, 7 months-10 years). There was no statistically
      significant difference between the 2 groups with regard to the number of
      patients, sex, age, and follow-up period. RESULTS: The percentage of patients who
      became seizure-free was higher in the surgical group than in the medical group
      (80% vs 19%, P < .01). The number of anticonvulsants required was reduced in the
      surgical group after surgery (from 1.5 +/- 0.7 to 1.1 +/- 0.8, P < .01) and was
      not reduced after in the medical group. CONCLUSIONS: Surgical intervention may
      have greater benefits than medical intervention for patients with cavernous
      angiomas presenting with epileptic seizures.

PMID- 16293462
TI  - Neuropsychological findings in patients with intraventricular tumors.
AB  - BACKGROUND: Intraventricular tumors are quite rare and become symptomatic with
      hydrocephalus-related signs such as headache, double vision, and seizures. Also,
      most of the patients show neuropsychological deficits, especially memory problems
      and lack of attention. METHODS: We reviewed the charts and computed
      tomographic/magnetic resonance images of 15 patients with tumors of the lateral
      and third ventricle, who were also examined by a neuropsychologist pre- and
      postoperatively. Neuropsychological testing included tests of attention, memory,
      executive functions, and concentration. RESULTS: Between 1995 and 2003, 7
      patients with colloid cysts of the third ventricle (3 men, 4 women; mean age, 38
      years), 5 patients with meningiomas of the lateral ventricle (2 men, 3 women;
      mean age, 51 years), and 3 patients with astrocytomas and ependymoma (2 men, 1
      woman; mean age, 38 years) were treated. All patients with colloid cysts and
      meningiomas showed mental changes, especially attention and memory deficits.
      Symptoms improved markedly after surgical intervention. The 3 patients with
      astrocytoma and ependymoma showed normal results pre- and postoperatively.
      CONCLUSION: Neuropsychological testing is very useful in patients with
      intraventricular lesions and important for follow-up examinations. It should be
      included in every workup examination in this small patient group.

PMID- 16293463
TI  - Outcome of surgical clipping for ruptured, low-grade, anterior circulation
      cerebral aneurysms: should clipping be omitted after International Subarachnoid
      Aneurysm Trial?
AB  - BACKGROUND: A recent randomized trial for ruptured aneurysm resulted in poorer
      outcomes for the surgical group than the endovascular group. However, the
      surgical results seemed to be worse than could be expected for experienced
      neurosurgeons in Japan. We therefore analyzed our own surgical results and
      evaluated them for a comparison with the trial results. METHODS: Data on patients
      with ruptured, small, anterior circulation aneurysms in good clinical condition
      (World Federation of Neurological Surgeons grade I or II) and treated with
      surgical clipping were obtained from various discharge databases for 1997 to
      2001, and their outcomes were analyzed in a retrograde fashion. RESULTS: Of the
      total of 487 patients, 17.6% showed a poor outcome (modified Rankin Scales 3-6)
      at discharge, and after 1 year, 6.1% remained in poor clinical condition.
      However, fewer patients were in poor condition both at discharge and after 1 year
      compared with the surgical and endovascular results for patients entered in the
      International Subarachnoid Aneurysm Trial. Complete occlusion of the aneurysm was
      attained in 93.6% of our patients. Rebleeding from the treated aneurysm occurred
      in 0.6%, and there was no rebleeding after 1 year. CONCLUSIONS: Surgical clipping
      is a safe and reliable treatment and can be the first choice for small ruptured
      aneurysms of the anterior circulation with a good grade.

PMID- 16293467
TI  - Plasma interleukin 11 levels correlate with outcome of spontaneous intracerebral
      hemorrhage.
AB  - BACKGROUND: Interleukin (IL) 11 is a multipotential cytokine with anti
      inflammatory and fibrogenic properties. It is released into the peripheral blood
      from damaged brain tissue. The objective of this study was to determine plasma
      and cerebral spinal fluid (CSF) levels of IL-11 in patients with spontaneous
      intracerebral hemorrhage (ICH) and to correlate IL-11 with survival, related
      edema of the brain, volume of hematoma, and hydrocephalus. METHODS: Forty-three
      patients with spontaneous ICH were included. Twenty-three were male, and 20 were
      female. The mean age of the patients was 64.3 years. Plasma and CSF samples were
      collected on the first, second, third, and fourth days after spontaneous ICH
      onset. RESULTS: The levels of IL-11 in CSF (123.9 +/- 107 pg/mL) were 5 times
      higher than those in plasma (25.5 +/- 18.0 pg/mL) on the first day (P = .001 by
      paired t test) in our spontaneous ICH patients, and this significant difference
      persisted up to the third day of ICH. Plasma IL-11 levels in the nonsurvival
      group (41.2 +/- 18.9 pg/mL) were significantly higher than those in the survival
      group (22.2 +/- 15.2 pg/mL) on the second day of ICH onset (P = .024 by Mann
      Whitney U test), and the significant difference extended to the fourth day.
      Plasma IL-11 levels of the hydrocephalus group were higher than those of the
      nonhydrocephalus group in the first 4 days of ICH, but the difference was not
      statistically significant. CONCLUSIONS: IL-11 was highly associated with
      mortality caused by spontaneous ICH and correlated with the hydrocephalus
      occurring after ICH onset. It is our belief that IL-11 can be a useful clinical
      marker for spontaneous ICH patients.

PMID- 16293471
TI  - Three-dimensional computed tomography-guided multitract aspiration of extensive
      ganglionic hemorrhage: technical note.
AB  - BACKGROUND: We describe a methodology for effectively improving the lysis and
      drainage of intracerebral hematomas during stereotactic surgery. METHODS:
      Stereotactic aspiration using a multitrack technique was performed in 20 patients
      with ganglionic hemorrhages perforating into the subcortex. Using 3-dimensional
      computed tomography (3D-CT) guidance, the trajectories and targets of hematoma
      drainage were selected to extract most portions of the irregular and expansive
      intracerebral hematomas. Volumes ranged from 36 to 60 mL (mean, 45 mL). Four to 5
      drains were inserted into the parenchymal and ventricular clots. Aspiration and
      injections of urokinase (5000 IU) were repeated every 2 to 3 hours until the
      hematoma was almost completely removed. RESULTS: The intended catheters for
      hematoma aspiration were placed precisely along the predetermined tracks with the
      aid of 3D-CT visualization. The deep and subcortical hematomas were totally
      removed within a mean of 10 hours postoperatively. Multiple catheter placements
      itself caused no complications. Sixteen patients (80%) recovered with a favorable
      neurological outcome. CONCLUSIONS: The 3D-CT-based multitrack technique is a
      rapid and effective method for the stereotactic removal of extensive ganglionic
      hemorrhages. It has the advantage of giving better neurological recovery than
      conventional stereotactic or microscopic surgery for selected patients.

PMID- 16293473
TI  - A patient with an odontoid fracture and atrophy of the tongue: a case report and
      systematic review of the literature.
AB  - BACKGROUND: Traumatic hypoglossal nerve palsy is a rare entity and has rarely
      been described in association with an odontoid fracture. CASE DESCRIPTION: We
      present a patient with a posttraumatic odontoid fracture who developed selective
      weakness of his arms and a unilateral hypoglossal nerve palsy. A systematic
      review of the literature is presented, and hypothetical causes for the injury are
      discussed. CONCLUSION: Bell's cruciate paralysis and central cord syndrome are
      probably expressions of the same mechanism rather than 2 separate entities based
      on a preferential damage of pyramidal crossing arm fibers. C2 fractures with
      concomitant lower cranial nerve injury are relatively rare and have a reasonably
      good outcome, especially when unilateral.

PMID- 16293476
TI  - Aneurysms located at the proximal anterior cerebral artery and anterior
      communicating artery associated with middle cerebral artery aplasia: case report.
AB  - BACKGROUND: Aneurysms arising from the proximal anterior cerebral artery (ACA)
      are quite rare. Here, we report upon such a case of aneurysms located at the
      proximal ACA and anterior communicating artery associated with middle cerebral
      artery (MCA) aplasia. CASE DESCRIPTION: A 64-year-old woman complained of severe
      headache. Brain computed tomography scans demonstrated acute subarachnoid
      hemorrhage. Angiograms showed 2 aneurysms located at the anterior communicating
      artery and proximal ACA, but did not show an MCA shadow on the lesion side.
      Instead, multiple collateral vessels ran toward the sylvian fissure and supplied
      the MCA territory, together with hypertrophied perforating branches. The
      operative findings confirmed that the cordlike rudimentary MCA had no internal
      blood flow. The 2 aneurysms were secured by neck clipping. CONCLUSION: The
      combined effects of these anomalies on the hemodynamic equilibrium of the
      arteries and the genesis of the aneurysms are noteworthy.

PMID- 16293477
TI  - A saccular-like dissecting aneurysm of the anterior cerebral artery that
      developed 2 years after an ischemic event.
AB  - BACKGROUND: A rare case of a growing dissecting aneurysm, which was located at
      the horizontal (A1) segment of the anterior cerebral artery (ACA), is reported.
      CASE DESCRIPTION: A 53-year-old woman experienced left hemiparesis and alien hand
      syndrome. A computerized tomography scan showed an infarction in the right
      frontal lobe, and cerebral angiography revealed a false lumen and intimal flap at
      the A1 segment of the ACA. Magnetic resonance angiography demonstrated that the
      stenosis progressed 6 months later and improved 1 year later. Cerebral
      angiography showed a saccular-like aneurysm 2 years later. The surgery was
      planned for prevention of aneurysmal rupture. The aneurysm, which was cocoon
      shaped, was exposed surgically and was resected. Histological examination of the
      aneurysm showed arterial dissection. The postoperative course was uneventful
      without additional neurological deficits. CONCLUSION: This is the first case
      report of A1 dissecting aneurysm presenting with an ischemic event in the
      literature. The sequential change of the configuration was curious to develop
      aneurysmal dilatation in 2 years. Long-term follow-up is necessary even after
      disappearance of the arterial dissection.

PMID- 16293480
TI  - Creutzfeldt-Jakob disease acquired via a dural graft: failure of therapy with
      quinacrine and chlorpromazine.
AB  - BACKGROUND: Accidental transmission of Creutzfeldt-Jakob disease (CJD) has been
      reported after neurosurgical interventions, use of intracerebral electrodes,
      corneal transplants, and after the administration of human-derived hormones.
      Acquired CJD has also been documented after dural grafting with tissues of human
      cadaver origin. At present, quinacrine and chlorpromazine are being investigated
      for the treatment of sporadic CJD, with the hope of offering an effective
      treatment of an otherwise fatal disease. Our objective was to report a case of
      iatrogenic CJD occurring 18 years after the implant of a dural graft of human
      origin and to inform on the results of the treatment with quinacrine and
      chlorpromazine. CASE DESCRIPTION: In 1984, a 46-year-old woman was given a
      Lyodura graft for decompression of Chiari I malformation and syringomyelia. The
      patient was diagnosed with CJD in 2002. In view of the scarce options for
      treatment of CJD and after reviewing the current literature, the patient was
      treated with quinacrine and chlorpromazine. She showed no clinical improvement
      and died 6 months after hospital admission. The iatrogenic origin of the disease
      in this patient is supported by the clinical features, laboratory data, and
      findings from the brain necropsy. CONCLUSIONS: Patients who have received a dural
      graft of cadaveric origin may be at risk for developing CJD after very prolonged
      incubation periods. Treatment with quinacrine and chlorpromazine for acquired CJD
      was ineffective in our patient. A clinical trial on the use of antiprion agents
      is warranted.

PMID- 16293482
TI  - Angiographic catheter: unique tool for neuroendoscopic surgery.
AB  - BACKGROUND: Neuroendoscopic removal of intraventricular and juxtaventricular
      space-occupying lesions (SOL) requires long and thin instruments that can be
      maneuvered through the compromised working channels. Currently, various rigid and
      flexible forceps and scissors are being used for this purpose. We present our
      experience of using cut segment of angiographic catheters for removal of
      intraventricular and juxtaventricular SOL by neuroendoscopic surgery. METHOD:
      Seventy-one patients having intraventricular and juxtaventricular lesions were
      excised, decompressed, or biopsied by endoscopic method using angiographic
      catheters. Lesions were cystic, solid, or mixed cystic and solid. Cystic lesions
      were aspirated; solid tumors were biopsied, decompressed, or excised by sucking
      them using 5F to 8F angiographic catheters cut to the length of 30 to 35 cm.
      RESULT: Total excision, near total removal, and biopsy of the lesions could be
      achieved in 14, 19, and 38 patients, respectively; however, in 2 patients of
      thalamic tumor, the biopsied tissue was negative for tumor. Tumor consistency was
      the deciding factor for their removal by angiographic catheters; soft lesions
      were sucked easily, whereas only biopsy could be done in firm and nonsuckable
      lesions. Major bleeding in a case of craniopharyngioma was the complication
      managed by irrigation followed by external ventricular drain. CONCLUSION:
      Angiographic catheter is a simple and unique tool for neuroendoscopic surgery. It
      aids in endoscopic management of diverse intraventricular and juxtaventricular
      lesions.

PMID- 16293483
TI  - How can I adapt to a rapidly changing world?

PMID- 16293484
TI  - The role of computed tomography scanning in abdominal trauma: an update.

PMID- 16293485
TI  - Emerging antibody therapy in organ transplantation.

PMID- 16293486
TI  - The mangled extremity: limb salvage versus amputation.

PMID- 16293487
TI  - Choice of practice.

PMID- 16293489
TI  - Identity theft and the academic curriculum vitae: how do I know you are who you
      say you are?

PMID- 16293490
TI  - The surgical management of locoregional and metastatic colorectal cancer
      recurrences.

PMID- 16293493
TI  - Middle-aged man with penetrating trauma to the pancreaticoduodenal complex.

PMID- 16293494
TI  - Rudolph Matas: the father of vascular surgery.

PMID- 16293495
TI  - Anterior modification of Delorme procedure provides equivalent results to Delorme
      procedure in treatment of rectal outlet obstruction.
AB  - BACKGROUND: This study was designed to assess the results of the standard Delorme
      procedure versus an anterior modification of the Delorme procedure in the
      treatment of patients with rectal outlet obstruction secondary to internal
      intussusception with or without rectocele. STUDY DESIGN: A descriptive
      retrospective study from October 1997 to May 2001 was undertaken. Twenty-seven
      patients with symptoms of rectal outlet obstruction assumed to be caused by
      internal rectal prolapse or a combination of internal rectal prolapse and
      rectocele underwent surgical repair. Twenty-two patients had preoperative
      defecography and anal manometry. Thirteen patients had an anterior Delorme
      repair; 14 patients had a standard Delorme repair. Selection of procedure was
      chronologic with the standard Delorme undertaken in the earlier group.
      Preoperative and operative data were collected retrospectively. RESULTS: Twenty
      seven women, aged 29 to 94 (mean, 62.0 for anterior Delorme, 66.3 for Delorme)
      years were followed up for the duration of the study (mean follow-up, 15.9 months
      for anterior Delorme and 32.1 months for Delorme). Twelve patients (92.3%)
      reported a good to excellent overall result after the anterior Delorme procedure
      versus 14 patients (100%) in the Delorme group. Symptomatic improvement was
      observed in 85.7% of patients who had incomplete evacuation in the anterior
      Delorme group versus 90.9% in the Delorme group. Symptoms of constipation,
      bleeding, and the need to manually assist in defecation by pushing in the
      perineum or vagina improved in 100% of patients in both groups. Discontinuation
      of laxative use after the procedure was reported by 75% of patients in the
      anterior Delorme group versus 100% in the Delorme group. Eight patients
      experienced minor complications, 4 of these being urinary retention. In the
      postoperative period, no patients in the modified group experienced incontinence.
      Sixty three percent of the Delorme group experienced some sort of incontinence
      within the first 2 to 3 months (p = 0.038). CONCLUSIONS: An anterior modification
      of the Delorme procedure, which requires less operative dissection, can be
      performed with results nearly equivalent to those of the established Delorme
      procedure in the treatment of rectal outlet obstruction secondary to internal
      intussusception with or without rectocele.

PMID- 16293496
TI  - Combined resection of the duodenum and pancreas for locally advanced colon
      cancer.
AB  - Colorectal cancer invading adjacent organs is a frequent event occurring in 5.5%
      to 12% of all colorectal malignancies. Colon cancer directly invading the
      duodenum and pancreas is rare and may require combined resection of the colon,
      pancreas, and duodenum, which represents a complex operation with significant
      morbidity and mortality rates. In this article, a case of a 41-year-old patient
      with a right colon cancer directly infiltrating the duodenum and head of the
      pancreas is presented. The patient was treated by radical combined resection of
      the colon, duodenum, and pancreas. Pathological examination confirmed neoplastic
      invasion of the adjacent organs and absence of lymph node metastasis (T4N0). The
      patient recovered uneventfully. Patients with colorectal cancer infiltrating
      adjacent organs such as the duodenum and the pancreas should be treated by
      radical en bloc resection of the tumor. This procedure is the preferred treatment
      strategy because it seems to be associated with improved overall survival rates.

PMID- 16293497
TI  - External fixation for Charcot foot reconstruction.

PMID- 16293498
TI  - Commentary: The use of external fixation for treatment of complex lower extremity
      neuropathic arthropathy.

PMID- 16293499
TI  - Historical perspective and current management of traumatic injury to the
      extraperitoneal rectum and anus.

PMID- 16293500
TI  - Relative adrenal insufficiency among trauma patients in a community hospital.
AB  - BACKGROUND: The integrity of the hypothalamic-pituitary-adrenal (HPA) axis is a
      major determinant of the host response to stress. Recent studies have proven that
      low doses of hydrocortisone and fludrocortisone can significantly reduce
      mortality in patients with relative adrenal insufficiency (RAI) without
      increasing adverse events. STUDY DESIGN: This study was a retrospective chart
      review of patients in a community hospital who carried the diagnosis of both
      adrenal insufficiency and trauma. RESULTS: Over a 16-month period, the incidence
      of RAI among severely injured patients (injury severity score >/= 13) was 3%.
      Only 1 patient had the classic electrolyte findings of adrenal insufficiency, but
      all had vasopressor-dependent hypotension. Our patients had an average intensive
      care unit day stay of 37 days and were not tested for RAI on average until day 20
      of their intensive care unit stay. Random cortisol levels did not correlate with
      injury severity. Six patients (75%) had a positive hemodynamic response to
      steroids. CONCLUSIONS: Relative adrenal insufficiency after trauma is rare. In
      RAI, clear signs and symptoms are usually absent. The clinical diagnostic clue
      may be the unexplained hypotension and the resistance to inappropriately high
      doses of inotropes and vasoactive agents. The hemodynamic profile often shows a
      hyperdynamic state of high cardiac output and a low systemic vascular resistance.
      Baseline serum cortisol levels did not correlate with injury severity scores in
      this group of patients, which suggests a defect in the HPA axis. An intensive
      care unit day stay of greater than or equal to 20 days, ventilator
      dependence/acute respiratory distress syndrome, and a hyperdynamic state mandates
      consideration of endocrine testing to exclude RAI. Physiologic doses of
      hydrocortisone can reverse this potentially life-threatening syndrome.

PMID- 16293501
TI  - Recurrent aortoenteric fistula: case report and review.
AB  - Aortoenteric fistulas (AEFs) are abnormal communications between the aorta and
      the bowel most frequently resulting from prosthetic graft erosion. Despite
      advances in surgery and medical technology, these entities are still associated
      with significant morbidity and mortality for the patient. Multiple case reports
      and reviews have attempted to elucidate the nature of AEFs in an effort to better
      characterize and manage these entities. However, reports of recurrence of this
      process are extremely rare. In this article, we describe a unique case of
      recurrence of an AEF that was successfully managed with primary aortic oversew
      and bowel resection. We will also review the literature on AEFs with a
      comprehensive overview on background, presentation, diagnosis, and current
      management options.

PMID- 16293502
TI  - The remedial year in the general surgery board certification process: how
      effective is it?
AB  - BACKGROUND: The American Board of Surgery (ABS) intends to assure high standards
      for knowledge and experience in every graduate from an approved general surgery
      program. They have gone to great lengths to devise an optimal remediation process
      for every candidate failing to reach these standards. But what is the
      effectiveness of the remediation process? METHODS: ABS data outlined the history
      and development of the remediation process up to its current form. A core
      component of this process is a specifically structured additional year of
      training at selected institutions. Ten institutions, which were classified as
      outstanding by the ABS, received a standardized confidential questionnaire to
      collect data that included the institution's impetus to administer a remedial
      year (RY), organization of their RY, specific emphasis points, role of advisors,
      funding, and choice of RY candidates. Each institution was asked to mail a letter
      to their RY graduates, asking for their participation in a follow-up study aimed
      at characterizing the failing candidate. RESULTS: ABS data have been available
      since 1980. Pass rates for the qualifying written examination (QE) improved
      steadily from about 63% in 1985 to 78% in 2003. Pass rates for the certifying
      oral examination (CE) have been consistently around 75% since 1985 with
      improvement to just above 80% within the last 4 years. In 1995, a new ABS policy
      was announced requiring an additional year of structured training with specific
      elements. For the QE, the general pool pass rates continued their steady
      improvement. Although the results for RY candidates did reveal a 20% improved
      pass rate, they were still 30 percentage points lower when compared with the
      general pass rates. No improvement was noted in the CE results. In 2003, ABS
      enacted the latest policy change, which consists of an alternative pathway for
      QE. The initial experience for 2003 is disappointing. Less than 10 candidates
      have taken advantage of this alternative, and pass rates have not improved. The
      policy for CE was changed to allow 5 attempts (up from 3 attempts) in 5 years,
      and currently it is too early to determine the impact of this change. Nine of 10
      institutions agreed to participate in our study. They identified the essential
      elements of a successful RY. They also emphasized that CE remediation has to go
      beyond correction of simple knowledge deficits. And they characterized the ideal
      candidate for remediation. No RY graduates agreed to participate in the planned
      follow-up study to characterize the failing candidate. CONCLUSION: The RY process
      seems to have a valid potential if specific conditions are met. We do believe
      that differentiation is needed between the QE and the CE remedial year programs.
      Because the CE incorporates rhetorical skills, an emphasis should be placed on
      public speaking and presentation skills in a remedial year for the CE. We
      recommend several possible avenues for consideration: identifying the resident at
      risk and intervening during residency, incorporating the RY process into the
      ongoing practice routine of the individual candidate, and actively recruiting
      participation of candidates in a needs assessment study.

PMID- 16293505
TI  - Medical malpractice matters: medical record.

PMID- 16293506
TI  - Successful collaborative model for trauma skills training of surgical and
      emergency medicine residents in a laboratory setting.
AB  - OBJECTIVES: To determine whether interdepartmental educational and technical
      resources could be combined to successfully train surgery and emergency medicine
      residents in common diagnostic and therapeutic trauma skills outside the
      traditional hospital setting. DESIGN: Curriculum improvement survey. SETTING:
      Surgical Skills Laboratory, Temple University School of Medicine, Philadelphia,
      Pennsylvania. PARTICIPANTS: A total of 35 surgery residents (PGY 1 to 5) and 26
      emergency medicine residents (PGY 1 to 3). METHODS: Emergency medicine attendings
      used human volunteers to train surgery residents in Focused Assessment with
      Sonography in Trauma (FAST). Trauma surgery attendings used a porcine model to
      teach emergency medicine residents tracheostomy, peripheral venous cutdown,
      diagnostic peritoneal lavage, tube thoracostomy, and bilateral thoracotomy. Upon
      completion of the courses, all residents were surveyed using a 5-point Likert
      scale to assess this teaching model. RESULTS: The percentage of residents
      reporting an improvement in knowledge levels after the course increased
      significantly (p < 0.003) for all skill modules (FAST, 14% vs 73%; tracheostomy,
      20% vs 64%; peripheral venous cutdown, 25% vs 71%; diagnostic peritoneal lavage,
      16% vs 60%; tube thoracostomy, 42% vs 92%; thoracotomy, 15% vs 42%). A
      significant (p < 0.05) increase in comfort levels during performance of the
      procedures in the clinical setting was also anticipated for all skills modules
      (FAST, 11% vs 60%; tracheostomy, 12% vs 50%; peripheral venous cutdown, 15% vs
      31%; diagnostic peritoneal lavage, 12% vs 58%; tube thoracostomy, 35% vs 73%;
      thoracotomy, 0% vs 15%). PGY 1 to 4 surgery residents and PGY 1 and 2 emergency
      medicine residents perceived the greatest benefit (p < 0.05) from their
      respective courses. The overwhelming majority (89% to 100%) of surgery and
      emergency medicine residents felt the course was valuable and transferable to the
      clinical trauma setting. CONCLUSIONS: Interdepartmental collaboration between the
      Department of Surgery and Department of Emergency Medicine offered a unique
      training relationship that was a positive educational experience for all
      residents.

PMID- 16293508
TI  - Using the Morbidity and Mortality conference to teach and assess the ACGME
      General Competencies.
AB  - PURPOSE: The weekly Morbidity and Mortality (M&M) conference, a Residency Review
      Committee on Surgery required conference, is a hallmark of general surgery
      residency training. This conference has been used traditionally to teach and
      assess the ACGME General Competencies of patient care and medical knowledge. The
      author's department has changed the format of their weekly M&M conference so that
      it enables them to teach and assess residents also in terms of the ACGME General
      Competencies of practice-based learning and improvement, professionalism,
      interpersonal and communication skills, and systems-based practice. METHODS: Each
      Monday the chief resident on each teaching service compiles a list of patient
      discharges and deaths for the previous week. Although all deaths are presented,
      only significant patient complications are selected for the following week's M&M
      conference. This 2-week preparation period enables the resident, who was
      primarily involved in the care of the patient, to thoroughly review the case and
      prepare his/her presentation. At the conference, the resident presents the
      patient's history and discusses the complication or death, not only in terms of
      the patient care provided (traditional M&M model), but also it analyzes the case
      in terms of health-care systems problems that may have contributed to the
      patient's morbidity and/or mortality; patient safety issues; communication
      problems with the patient, family, or other health-care workers; and ethnic or
      ethical issues related to the care provided. The case is then reviewed by faculty
      surgeons. Again, not only is the patient care critiqued, but also systems
      problems, communication problems, and ethical dilemmas. Each resident who
      presents a case at the M&M conference also completes a practice-based improvement
      log. This form analyzes the patient's outcome including factors leading to the
      complication and/or mortality, opportunities for systems improvement, patient
      safety or communication problems, ethnic or ethical issues, what the resident
      would do different in his/her practice, and references consulted for this case.
      These forms are reviewed with the resident by the Residency Director and become
      part of the resident's portfolio. CONCLUSION: The restructuring of the M&M
      conference so that a case is analyzed with all ACGME General Competencies has
      made the M&M conference more interesting and has improved the educational aspects
      of the conference. Analyzing a case according to the various ACGME General
      Competencies has provided another method to teach these competencies to their
      residents and a tool to determine whether the residents are meeting the
      competencies.

PMID- 16293510
TI  - Principles of cancer prevention.
AB  - OBJECTIVE: To summarize the scientific principles underlying cancer prevention.
      DATA SOURCES: Articles, text books, personal communications, and experience.
      CONCLUSION: The scientific basis of cancer prevention is complex and involves
      experimental and epidemiologic approaches and clinical trials. IMPLICATIONS FOR
      NURSING PRACTICE: As more information becomes available regarding proven and
      potential cancer-prevention strategies, oncology nurses are regularly called upon
      to guide patients and others in making choices regarding preventative options. It
      is important for oncology nurses to stay abreast of this growing body of
      knowledge.

PMID- 16293511
TI  - Epidemiology of cancer in the United States.
AB  - OBJECTIVES: To describe the epidemiology of cancer in the United States-risk
      factors, trends, and recent patterns of disparities in cancer incidence,
      mortality, and survival. DATA SOURCES: Published articles, research reports and
      monographs, book chapters, government publications, and machine-readable public
      use data files. CONCLUSION: The discipline of cancer epidemiology has greatly
      increased our understanding of cancer risk, morbidity and mortality, survival,
      trends over time, and disparities in cancer treatment and outcomes. IMPLICATIONS
      FOR NURSING PRACTICE: Nursing can use epidemiologic tools to reduce the suffering
      and death caused by cancer and improve the quality of life for cancer survivors.

PMID- 16293512
TI  - Chemoprevention: a primary cancer prevention strategy.
AB  - OBJECTIVES: To review cancer chemoprevention clinical trials, and to discuss
      associated roles, responsibilities, and challenges for nursing. DATA SOURCES:
      Journal articles, textbooks, and government reports. CONCLUSION: Chemoprevention
      offers a promising approach to primary cancer prevention for a variety of organ
      systems. Candidate agents are rigorously evaluated for safety and efficacy
      through the chemoprevention clinical trials process. IMPLICATIONS FOR NURSING
      PRACTICE: Chemoprevention is an emerging discipline in which complex clinical
      trials are being conducted. Nurses play key roles in planning, coordinating, and
      implementing these studies.

PMID- 16293513
TI  - Secondary prevention of cancer.
AB  - OBJECTIVES: To review criteria for mass cancer screening among asymptomatic
      populations and barriers to secondary prevention of breast, cervical, and
      colorectal cancers. To describe challenges to implementing theoretically based
      interventions to increase appropriate cancer screening, follow-up, and
      surveillance. DATA SOURCES: Published journal articles, text books, and
      epidemiologic reports. CONCLUSION: Interventions to increase breast, cervical,
      and colorectal cancer screening participation must be approached from a systems
      perspective that includes patient, health care provider, and health care system
      variables. IMPLICATIONS FOR NURSING PRACTICE: Understanding the array of factors
      that impede progress in the secondary prevention of cancer is necessary to
      improve care. Nurses have an important role in decreasing morbidity and mortality
      from breast, cervical, and colorectal cancers.

PMID- 16293514
TI  - Tertiary prevention: implications for improving the quality of life of long-term
      survivors of cancer.
AB  - OBJECTIVE: To provide an overview of the incidence, epidemiology, and appropriate
      screening for second primary malignancies, as well as the nursing implications of
      tertiary cancer prevention. DATA SOURCES: Published review articles, book
      chapters, research reports, and the clinical experience of the author.
      CONCLUSION: Many persons successfully treated for malignancy are at risk for a
      second malignancy. This risk is related to shared risk factors, genetic
      predisposition, and the toxic effects of therapy. Persons particularly at risk
      are those who have been successfully treated for breast, gynecologic, colorectal,
      skin, and lymphoma malignancies. IMPLICATIONS FOR NURSING PRACTICE: Nurses need
      to be knowledgeable regarding the principles of tertiary prevention, be able to
      identify persons at risk, and provide appropriate patient education and
      psychosocial support on how to manage the risk and detect second malignancies
      early.

PMID- 16293515
TI  - Modifying cancer risk factors: the gene-environment interaction.
AB  - OBJECTIVES: To examine the concept of risk modification in the context of cancer
      prevention. DATA SOURCES: Published articles and research studies on genetic and
      environmental factors. CONCLUSION: How the environment is defined frames how the
      gene-environment interaction is studied and understood. The development of a
      workable model for risk modification flexible enough to be individualized for a
      patient is an important step in making primary prevention the goal in cancer
      care. IMPLICATIONS FOR NURSING PRACTICE: Nurses working in cancer care are well
      placed to advise patients on risk-management strategies, and to increase public
      awareness of the interdependence of environment and genomics on cancer risk.

PMID- 16293516
TI  - Cancer prevention among racial ethnic minorities.
AB  - OBJECTIVES: To provide an overview of the cancer disparities among racial and
      ethnically diverse populations and to describe primary and secondary prevention
      among them. DATA SOURCES: Published articles, reports, book chapters, and
      government documents. CONCLUSION: Despite the advances in cancer diagnosis,
      treatment, and survival, racial and ethnic minorities suffer disproportionately
      from cancer. Poverty has emerged as a significant factor influencing poor cancer
      outcomes for all races, but especially among racial and ethnic minorities.
      IMPLICATIONS FOR NURSING PRACTICE: Continued and sustained efforts are needed on
      all fronts (education, practice, and research, policy) to improve the poor cancer
      related outcomes for minorities.

PMID- 16293517
TI  - Public education and cancer control.
AB  - OBJECTIVES: To provide an overview of public education efforts in tobacco,
      obesity, environmental health, and cancer screening. DATA SOURCES: Cochrane,
      AHRQ, the CDC's Guide to Community Preventive Services, and other reviews.
      CONCLUSION: Major changes in rates of smoking and cancer screening attest to the
      effectiveness of public education efforts. Diet and physical activity have more
      resistant behaviors. Communication technologies offer possibilities for
      connecting people with the education they need. IMPLICATIONS FOR NURSING
      PRACTICE: Nurses can play important roles in public education by helping to
      overcome people's misperceptions and biases related to cancer. There also may be
      an important role for nurses as information brokers.

PMID- 16293518
TI  - The future of cancer prevention.
AB  - OBJECTIVES: To hypothesize on the future of cancer prevention based on past and
      current progress of the field, as well as possible assimilation of knowledge in
      other fields that may be applied to cancer prevention. DATA SOURCES: Peer
      reviewed research and federal government reports. CONCLUSION: Cancer prevention
      will exist in the future as an important public health strategy involving
      lifestyle and medical approaches that include behavior in relation to risk
      factors, chemoprevention, biomarker assessment, vaccines, and emerging
      technologies to better identify individuals at risk for cancer. IMPLICATIONS FOR
      NURSING PRACTICE: In the future nurses will play an enhanced role in cancer
      prevention through their efforts supporting risk assessment, education, and
      medical approaches in an expanded role with diagnostic testing, and support for
      prevention clinical trials.

PMID- 16293520
TI  - Oxidation of anthracene on platinum macro- and micro-electrodes:
      Sonoelectrochemical, cryoelectrochemical and sonocryoelectrochemical studies.
AB  - The electro- and sonoelectro-chemical oxidation of anthracene in acetonitrile has
      been explored at room and low temperature (-40 degrees C) at a platinum micro-
      and macro-electrode, respectively. From both methodologies, the effective number
      of electrons, n(eff), in the oxidation process is evaluated at both room
      temperature and at the limit of the solvent-electrolyte freezing point. It is
      observed that n(eff) is close to 1 at low temperature while at room temperature
      it is higher, indicating sluggish follow up kinetics at lower temperature. The
      oxidative electrolysis of anthracene within an undivided cell, under various
      conditions is investigated with the product(s) obtained analysed and quantified
      by (1)H NMR. At room temperature under both 'silent' and 'sono' conditions the
      electrochemical oxidation produces 9,10-anthraquinone and bianthrone while at low
      temperature with acoustic streaming, anthracene-9,10-diol is additionally
      produced. Electrolyses with intentionally added water and also with oxygen
      saturation is investigated and its influence on the reaction pathway reported. In
      particular, the addition of water (1.4M) favours the formation of anthraquinone
      in a 3:1 ratio with bianthrone. Overall, the effect of lower temperature is to
      favour the formation of anthraquinone or its reduced form whilst the addition of
      insonation at low temperature is to substantially enhance the product yield per
      Coulomb of charge injected.

PMID- 16293519
TI  - Nanoparticle decorated surfaces with potential use in glycosylation analysis.
AB  - A majority of all biologically active proteins are glycosylated and various
      diseases have proven to correlate with alterations in protein glycosylation.
      Sensitive identification of different glycoprotein glycoforms is therefore of
      great diagnostic value. Here we describe a method with potential for glycoprotein
      profiling, based on lectins as capture probes immobilized on particulate
      substrates in the nm-range. The nanoparticles present high concentrations of
      attachment sites for specific ligands and cause minimal steric hindrance to
      binding. In the present model study the mannose-binding lectin ConA has been
      coupled to polystyrene nanoparticles via a poly(ethyleneoxide) linker which
      protects the protein conformation and activity and prevents unspecific protein
      adsorption. The ConA-coated particles are accommodated at different spots on the
      analytical surface via oligonucleotide linkage. This attachment, which relies on
      the hybridization of complementary oligonucleotides, allows firm fixation of the
      particles at specific positions. The ConA attached to the particles has retained
      conformation and activity and binds selectively to a series of different
      glycoproteins. The results indicate the potential for using a multi-lectin
      nanoparticle array in glycoprotein mapping.

PMID- 16293521
TI  - Application of wavelet transform in pulsed ultrasonic modulation voltammetry.
AB  - In this study, wavelet transform was employed to achieve the different current
      components in pulsed ultrasonic modulation voltammetry. It was found that the
      pulsed sonovoltammograms could be decomposed into wavelet approximations and
      wavelet details by projecting wavelet transform on the signals in question. Since
      wavelet approximations with a certain scale parameter may retain the waveform of
      the original signal, the current components resulted from ultrasound "on" and
      "off" in pulsed sonovoltammograms could be separated at a certain scale parameter
      in multiplying wavelet approximation. With this method, the current components
      corresponding to pulse-on and pulse-off can be recorded separately without the
      external data acquisition system used in general modulation voltammetric
      measurements. The current difference between the two states was found to be
      proportional to the concentration of the electro-active species. The analytical
      usefulness of this approach was exploited for determination of ferrocyanide ion
      at sub-micromolar concentrations.

PMID- 16293522
TI  - The use of a micro-bubble agent to enhance rabbit liver destruction using high
      intensity focused ultrasound.
AB  - Liver tissues in New Zealand rabbits were ablated using high intensity focused
      ultrasound (HIFU, 14300 W/cm(2), 1.0 MHz). The animals were intravenously
      administered 0.2 ml of micro-bubble agent in the experimental (n=20) group and an
      isovolumetric normal saline solution in the control (n=27) group before HIFU
      treatment which was performed as a linear scan. In both groups, the preselected
      tissue volumes were destroyed without harming the overlying tissues. Necrosis
      rate (NR, cm(3)/s) was used to reflect the ablation efficiency, which was the
      tissue volume of occurring coagulative necrosis per 1s HIFU exposure. NR was
      improved in the experimental group (0.0570+/-0.0433 vs 0.0120+/-0.0122,
      P=0.0002). Pathological studies confirmed that there were no residual intact
      targets within the exposed volume. These findings suggested that the introduction
      of the micro-bubble agent enhanced HIFU liver destruction.

PMID- 16293523
TI  - Kinetics of ultrasonic extraction of extractive substances from garden (Salvia
      officinalis L.) and glutinous (Salvia glutinosa L.) sage.
AB  - The kinetics of ultrasonic extraction of extractive substances (ES) from dry
      herbs of garden (Salvia officinalis L.) and glutinous (Salvia glutinosa L.) sage
      using petroleum ether, 70% ethanol or water at 40 degrees C, as well as the
      composition of dry extracts, were studied. The mechanism of ultrasonic extraction
      is confirmed to occur in two steps: first, dissolution of the ES near the
      particle surface (washing) and, second, diffusion from the solid particles to the
      bulk of the liquid extract (slow extraction). The process is described
      mathematically using three concepts of the unsteady diffusion through plant
      material, the film theory and the empirical equation of Ponomaryov. The yield of
      ES increases with increasing solvent polarity, and nearly the maximum
      concentration of ES in liquid extracts is achieved for about 20 min. The
      composition of extracts depends on both the extraction conditions applied and the
      plant material.

PMID- 16293524
TI  - Effect of additives on ultrasonic degradation of phenol.
AB  - Sonication for phenol degradation has proved to be an attractive process over the
      years at least on a laboratory scale but the rates of phenol degradation under
      sonication have always been quite low. The present work investigates the use of
      simple additives such as salt and carbon tetrachloride as process intensifying
      parameters with an aim of reduction in the treatment times and hence the cost of
      operation. The intermediates formed in the degradation process have been analyzed
      and it has been observed that these intermediates degrade faster as compared to
      phenol. A hybrid technique of ozonation coupled with cavitation has also been
      investigated with an objective of finding the optimum conditions for the
      combination of ozonation and cavitation for synergistic effects. Analysis of the
      intermediates for the combination treatment scheme also indicates that the
      intermediates (hydroquinone, catechol, resorcinol, maleic acid, acetic acid,
      oxalic acid, formic acid, etc.) are more biodegradable prompting a possible
      combination of cavitation with aerobic oxidation for large scale treatment of
      phenol containing waste.

PMID- 16293525
TI  - Ultrasound assisted synthesis of delta-chloroesters from tetrahydrofuran and acyl
      chlorides in the presence of catalytic zinc dust.
AB  - Sonication of acyl chlorides and dry tetrahydrofuran (THF) in the presence of
      catalytic amounts of zinc dust at 35 kHz gives delta-chloroesters in high yields.

PMID- 16293526
TI  - Parkinsonism caused by cavernoma located in basal ganglion.
AB  - Deep-seated cavernoma or cavernous angioma is a very rare clinical entity, as is
      basal ganglia cavernoma presenting with Parkinsonism. The authors demonstrate a
      56-year-old man with a cavernoma located in basal ganglion, who subsequently
      developed Parkinsonism. The patient refused the surgical intervention, and
      received L-dopa trial; however, no change in the tremor and bradykinesia was
      observed in spite of high doses of L-dopa. Our case indicates that chronic
      compression and continuous hemorrhage could cause Parkinsonism, which is uncommon
      symptom of cavernous angioma.

PMID- 16293527
TI  - Early impairment of myocardial function in systemic sclerosis: non-invasive
      assessment by Doppler myocardial and strain rate imaging.
AB  - BACKGROUND: Aim of the present study was to analyze both left (LV) and right
      ventricular (RV) myocardial function in patients with Systemic Sclerosis (SSc),
      and their relation to other instrumental features of the disease. METHODS AND
      RESULTS: Twenty-five healthy subjects and 23 age- and sex-comparable asymptomatic
      patients classified as having either diffuse (11 patients) or limited form (12
      patients) of SSc underwent clinical examination, serological tests, high
      resolution chest-CT, standard Doppler echo, pulsed Doppler myocardial imaging
      (DMI) and strain rate imaging (SRI) of both LV and RV lateral walls. By chest-CT,
      11 patients showed interstitial pulmonary fibrosis. Serological antibodies
      analysis detected anti-centromere pattern in 8 patients, and anti Scl-70 in 15
      patients. LV diameters and ejection fraction were comparable between the two
      groups, while RV end-diastolic diameter was increased in SSc (p<0.01). Tricuspid
      inflow E/A ratio was slightly decreased in SSc (p<0.01), while systolic pulmonary
      pressure was increased (p<0.001). Pulsed DMI detected in SSc impaired myocardial
      RV early-diastolic (Em) peak velocity (p<0.0001), and prolonged myocardial time
      intervals at tricuspid annulus level. In SSc, peak systolic RV SR and strain were
      both reduced in basal, middle and apical RV lateral free walls, and in basal and
      middle LV lateral walls. By multivariate analysis, independent inverse
      association of RV peak Em velocity with both Rodnan Skin Score (p<0.0005) and
      pulmonary systolic pressure (p<0.0001), as well as independent inverse
      correlation of the same RV peak Em velocity with pulmonary fibrosis (<0.0005) in
      SSc patients were observed. In addition, RV Em was an independent predictor of
      the anti Scl-70 antibody pattern (p<0.001). CONCLUSIONS: Pulsed DMI and SRI are
      valuable non-invasive and easy-repeatable tools for detecting RV and LV
      myocardial involvement caused by SSc, and may therefore be useful to early
      identify patients with more diffused and severe form of SSc.

PMID- 16293528
TI  - The E/e filling index and right ventricular pressure in relation to applied
      international Doppler recommendations of left ventricular filling assessment.
AB  - AIM: A ratio>15 between the early diastolic pulsed Doppler velocities of the
      mitral inflow (E) and the basal left ventricular (LV) tissue (e) has been
      demonstrated to predict an elevated LV filling pressure (FP). An elevated LVFP
      implies an elevated right ventricular pressure (RVp). In order to investigate the
      sensitivity of the E/e filling index, we compared E/e and RVp, in their ability
      to identify a Doppler-assumed elevation of LVFP. METHODS AND RESULTS: Application
      of pulsed Doppler international recommendations grouped 134 patients with acute
      coronary syndromes (ACS) and 50 age- and sex-matched controls, according to LV
      filling: normal; delayed relaxation; an isolated pathological mitral-pulmonary
      venous-A-wave-duration difference; pseudo normal; or a restrictive filling
      pattern. An E/e>15 and an RVp>30 mmHg showed the following (%) sensitivity
      (32/94), specificity (95/76), positive (68/59), and negative (80/97) predictive
      values of a Doppler-assumed elevation of LVFP, in terms of either a pseudo normal
      or a restrictive filling pattern. CONCLUSION: The low sensitivity of E/e to
      detect a Doppler-assumed elevation of LVFP could limit its clinical usefulness as
      a single variable, in ACS. The high sensitivity and negative predictive value of
      RVp support its use as an additional LV filling variable in these patients.

PMID- 16293529
TI  - Right vs. left ventricular contractile reserve in one-year prognosis of patients
      with idiopathic dilated cardiomyopathy: assessment by dobutamine stress
      echocardiography.
AB  - AIM: To determine prognostic implications of the assessment of right (RV) vs.
      left ventricular (LV) contractile reserve with dobutamine echocardiography in
      patients with idiopathic dilated cardiomyopathy. METHODS AND RESULTS: Forty-eight
      consecutive patients (41 male, NYHA class III/IV 13 patients, LV ejection
      fraction 19+/-8%) were subjected to dobutamine stress echocardiography in
      incremental stages lasting 5 min each. Contractile reserve was defined as the
      difference between the values of LV ejection fraction and RV fractional area
      change obtained at peak dobutamine dose and the baseline values. Patients were
      followed for one year after enrollment for combined end-point of cardiac death,
      partial left ventriculectomy and hospitalization for congestive heart failure.
      During the follow-up 15/48 patients reached combined end-point. Patients who
      reached end-point had lower RV and LV contractile reserves (14+/-5 vs. 8+/-6%,
      p=0.0014, and 9+/-5 vs. 3+/-2%, p<0.001, respectively). Kaplan-Meier curves
      demonstrated that both LV and RV contractile reserves can identify patients with
      dismal prognosis (log rank=17.02 and log rank=14.66, respectively, p<0.001 for
      both). Multivariate analysis identified dobutamine induced change in LV
      functional reserve as the only independent predictor of combined end-point (beta=
      0.63, p=0.0035). CONCLUSION: Both RV and LV contractile reserves can be used for
      prognostic stratification in patients with idiopathic dilated cardiomyopathy. It
      appears that dobutamine induced change in LV functional reserve may better
      identify patients with dismal prognosis.

PMID- 16293530
TI  - Mitral valve repair versus replacement for isolated non-ischemic mitral
      regurgitation in patients with preoperative left ventricular dysfunction. A long
      term follow-up echocardiography study.
AB  - The aim of this study was to evaluate LV function, by means of echocardiography,
      after mitral valve repair (MVr) or mitral valve replacement (MVR) in patients
      (pts) with chronic degenerative mitral regurgitation (MR) and depressed LV
      systolic function during a 6-years follow-up (FU) period. PATIENTS AND METHODS:
      Forty-five pts with moderately severe or severe MR and preoperative EF<or=50%
      were divided into 2 groups: MVr group (27 pts, 19 men-8 women, aged 62+/-10
      years) and MVR group (18 pts, 8 men-10 women, aged 60+/-12 years). The cause of
      MR was myxomatous mitral valve disease (MVr/MVR: 16/8), endocarditis (0/4) and
      degenerative mitral valves with ruptured chordae tendineae (11/6). All pts
      underwent transthoracic echocardiography preoperatively, postoperatively and
      annually during the FU period (6+/-3 years). RESULTS: In MVr group, 5 pts died, 5
      were lost to FU and 2 pts underwent MVR due to MVr failure. In MVR group, 6 pts
      died, 3 were lost to FU and 1 was re-operated due to prosthetic valve
      endocarditis. Atrial fibrillation was similar between the 2 groups. MVr pts
      demonstrated significant LVEDD decrease postoperatively which was persistent
      during FU (p<0.05). LVESD also decreased (p<0.05), VTI improved (p<0.05), while
      FS and EF showed a trend to improve. In MVR pts, LVEDD was decreased (p<0.05) but
      increased during FU (p<0.05) and LVESD remained high, resulting in a decrease of
      FS and EF (p<0.05). VTI remained unchanged (p=NS). CONCLUSION: MVr in pts with
      non-ischemic MR and preoperative LV dysfunction achieves better preservation of
      LV systolic indices than MVR, probably due to preservation of the subvalvular
      apparatus and LV geometry.

PMID- 16293531
TI  - Three-dimensional echocardiography in mitral valve disease.
AB  - Three-dimensional echocardiography offers great promise for improving the
      understanding of the mitral valve anatomy, function, and pathology. It may have
      important implications for medical or surgical management of different mitral
      valve disease. In this article we provide an overview of the three-dimensional
      anatomy of the mitral valve. Based on the studies using three-dimensional
      echocardiography we describe the topography of the mitral valve, its nonplanarity
      as well as dynamics of the mitral annulus. Furthermore, we review the use of
      three-dimensional echocardiography in the evaluation of different mitral valve
      disease. Three-dimensional echocardiography has become a new clinical standard in
      the assessment of the severity of mitral stenosis by means of accurate mitral
      valve area measurement. Also, unconventional indices, like the geometry and
      mitral valve volume may be assessed by three-dimensional echocardiography. It is
      a very suitable technique for monitoring the efficacy and complications of
      percutaneous mitral valvuloplasty. Three-dimensional echocardiography allows
      accurate identification and quantification of prolapse of individual segments of
      the mitral valve leaflets. Three-dimensional color flow imaging makes
      echocardiography an accurate method also in the assessment of mitral
      regurgitation severity. Finally, we outline three-dimensional echocardiography as
      a potentially useful guide for a surgeon, particularly in mitral valve repair.

PMID- 16293532
TI  - Benefit of cardiac resynchronization therapy to a patient with a narrow QRS
      complex and ventricular dyssynchrony identified by tissue synchronization
      imaging.
AB  - This report described an 81-year-old woman with severe symptomatic heart failure,
      reduced ejection fraction, mitral regurgitation, and an electrocardiographic QRS
      width of 118 ms who had ventricular dyssynchrony identified by echocardiographic
      tissue synchronization imaging. Because of her severe heart failure symptoms on
      maximal medical therapy, referral to implant a defibrillator, and mechanical
      dyssynchrony, she underwent cardiac resynchronization-defibrillator therapy with
      lateral left ventricular lead placement. This resulted in an immediate 30%
      increase in stroke volume and 35% decrease in mitral regurgitation.
      Echocardiographic tissue synchronization imaging may play a role in identifying
      mechanical dyssynchrony in patients with narrow QRS duration who may potentially
      benefit from cardiac resynchronization therapy.

PMID- 16293533
TI  - Different deformation patterns in intracardiac tumors.
AB  - We report on the ultrasound characteristics of two different intracardiac tumors
      in newborns. The first infant presented with multiple rhabdomyomas in the context
      of tuberous sclerosis. Ultrasound-based strain and strain rate analysis showed
      that the tumors deformed in the opposite direction from the surrounding
      myocardial segments. The second child presented with a large cardiac fibroma as
      confirmed by pathological examination. In this case strain and strain rate
      analysis showed the absence of deformation in the tumor. These findings suggest
      that this new technique could be used to differentiate between different types of
      myocardial tumors.

PMID- 16293534
TI  - Contrast echocardiography for perfusion in right ventricular cardiomyopathy.
AB  - Right ventricular (RV) cardiomyopathy is a familiar myocardial disease of RV
      characterized by extensive fatty replacement of the myocardium. Conventional
      echocardiography is able to show abnormalities in myocardial contractility, but
      fat on the images appears to be similar to the surrounding tissue or fluid. The
      present case suggests the clinical role of contrast echocardiography showing
      perfusion abnormalities in patients with RV cardiomyopathy in the region of the
      fat depositions.

PMID- 16293535
TI  - What does potency actually mean for inhaled corticosteroids?

PMID- 16293536
TI  - Validation of a single concentration methacholine inhalation provocation test
      (SCIPT) in children.
AB  - A new method to assess bronchial hyperresponsiveness (BHR) using a single
      concentration methacholine has already been validated in adults with asthma.
      Because the geometrical dimensions of the airways in children are different, the
      results from studies in adults cannot be extrapolated to children. In this study,
      we validated the single concentration methacholine inhalation provocation test
      (SCIPT) in children. Twenty-two children performed three methacholine inhalation
      challenge tests in random order. Two challenges were performed according to the
      SCIPT: doubling doses (0.03-1.8 mg; maximal cumulated dose 3.6 mg) were
      administered with an Aerosol Provocation System (Masterscope, Jaeger). The third
      challenge was performed according to a standard dosimeter method (SDM): doubling
      doses (0.002-1.8 mg; maximal cumulative dose 3.5 mg) were administered with a
      DeVillbiss 646 nebulizer. The degree of BHR is expressed as a PD20. A difference
      of < 1.5 dose step was assumed to be due to intraindividual variation. We found
      an intraclass correlation of 0.91 between both tests according to the SCIPT and
      of 0.80 between the SCIPT and SDM. We found, according to the method of Bland and
      Altman, good agreement when comparing these two challenge tests. The single
      concentration inhalation provocation test is reproducible and shows good
      agreement with a standard dosimeter method to test bronchial responsiveness in
      children.

PMID- 16293537
TI  - Identifying risk and resource factors in children with asthma from urban
      settings: the context-health-development model.
AB  - This two-year longitudinal study examined concurrent and across-time associations
      between characteristics related to context, health, and development (i.e.,
      neighborhood disadvantage, knowledge related to asthma management and asthma
      management behaviors, and self-competence) and children's asthma-related
      functioning. Thirty-one 8- to 12-year-old children with asthma and their primary
      caregivers were interviewed for the baseline of this study, and 29 of these dyads
      were interviewed for the 1-year follow-up. All participants resided in urban
      neighborhoods, and most were members of ethnic minority (African American and
      Hispanic) groups. Cross-sectional support was found for significant inverse
      relationships between neighborhood disadvantage and children's asthma knowledge.
      Lower levels of self-competence were consistently cross-sectionally associated
      with lower levels of asthma knowledge. A combination of higher levels of asthma
      knowledge, more optimal asthma management strategies, and self-competence was
      associated with fewer school absences across the study period. These results
      suggest an interdependence between aspects of children's sociocultural context,
      health, and developmental characteristics. This multidimensional model provided
      preliminary support for the risk function of neighborhood disadvantage and the
      resource functions of asthma knowledge, asthma management, and self-competence
      for asthma-related functioning among urban children.

PMID- 16293538
TI  - Clinician-assessed poor compliance identifies adults with severe asthma who are
      at risk of adverse outcomes.
AB  - Our aim was to determine whether clinician-identified poor compliance is useful
      in identifying, from among adults with severe asthma, patients with
      characteristics likely to put them at risk of adverse outcomes. Patients with
      severe asthma (previous hospital admissions and/or prescribed step 4-5 treatment
      according to British Thoracic Society guidelines) considered by clinicians to be
      either compliant (C, N = 41) or poorly compliant (PC, N = 92) with aspects of
      their recommended management (attendance at appointments, taking medication, and
      monitoring asthma) provided data on symptoms, health service use, medication,
      self-management practices, physical and psychological comorbidities, and
      sociodemographic/socioeconomic characteristics. Cross-sectional univariate
      analyses were used to examine whether the groups differed with respect to self
      reported indicators of asthma morbidity and self-management. Logistic regressions
      were additionally used to explore psychosocial factors independently associated
      with patients being identified as PC. Compared with C patients, PC patients had
      significantly poorer self-reported asthma control in terms of medication use,
      symptoms, time off work, asthma-specific quality of life, primary care visits,
      emergency attendances, and hospital admissions. This was coupled with poorer self
      management practices. Patients identified as PC also had higher levels of
      physical and psychological comorbidities, were younger, and faced more difficult
      social and economic circumstances. We identified significant psychological
      (anxiety) and social (younger age, not working, number of benefits, adverse
      family circumstances) factors independently associated with patients being
      identified as PC. Among adults with severe asthma, clinician-assessed poor
      compliance was useful in distinguishing between two groups that differed
      significantly in terms of asthma morbidity indicators, self-management practices,
      and psychosocial characteristics, which have been previously shown to be
      associated with hospital admissions, near-fatal attacks, and fatal asthma. We
      conclude that clinician-assessed poor compliance is a useful marker for
      identifying patients at risk of these adverse outcomes.

PMID- 16293539
TI  - A descriptive analysis of asthma-related medical services and prescription
      utilization among recipients in a Medicaid program.
AB  - One objective of the Healthy People 2010 initiative calls for the establishment
      of a surveillance system to track asthma illness and management in at least 25
      states. Our objective was to report patterns of asthma-related medical services
      and pharmacotherapy use among recipients of Texas Medicaid. Texas Medicaid
      medical services and prescription administrative claims data dated between
      January 1 and December 31, 2000, for recipients between 6 and 64 years of age
      enrolled in a fee-for-service plan were extracted. Rates of recipients with
      asthma, rates of asthma-related medical services use, and patterns of
      pharmacotherapy use were reported. There were 31,509 recipients identified with
      asthma at a rate of 22.8 per 1000. Children under 15 years of age, males, and
      blacks had the highest rates of asthma, as well as asthma-related emergency
      department (ED) visits and hospitalizations compared with other demographic
      groups. Hispanics accounted for the largest proportion of ethnic groups but had
      the lowest rate of asthma compared with whites and blacks. The rate of ED visits
      and hospitalizations among children was more than twice the rate among adults.
      Blacks had more than twice the rate of ED visits and nearly double the rate of
      hospitalizations for asthma compared with other ethnic groups. Roughly 56% of the
      recipients had a claim for an inhaled anti-inflammatory medication. However, it
      appeared that recipients were using short-acting beta-agonists more frequently
      than inhaled corticosteroids. Use of medical services and prescription
      medications for asthma varied greatly on the basis of recipient demographic
      factors.

PMID- 16293540
TI  - A self-management program for adult asthma: part IV, Analysis of context and
      patient behaviors.
AB  - Patient behaviors performed in the self-management of asthma have been
      investigated by use of black box theory as a model for examining behavioral
      change. Consequently, the context within which patients learn and perform
      processes of self-management has been ignored. The purpose of the present study
      was to investigate contextual and behavioral elements that comprise the
      management of asthma attacks by a large number of adult patients. A total of 3442
      reports of attack were obtained from 90 subjects, including 76 patients described
      in the article by Kotses and colleagues, 9 who dropped out of the study, and 5
      who served as pilot subjects. The major focus of the analysis, however, was on
      the 63 subjects who submitted forms during two periods: intake/baseline and
      training/after training. Data included information about the episode (e.g.,
      severity, duration, etc.), prior actions taken by patients (e.g., adherence to
      treatment regimens, collection of peak flow data, etc.), and the impact of
      contextual variables (e.g., setting where attack occurred, time when attack
      occurred, etc.) on patient behaviors The variables were subjected to a
      probability analysis to demonstrate changes in the probability of responses as
      influenced by contextual variables present during any given attack. The results
      indicated that contextual variables affect behavioral change. Changes occurred in
      actions taken to manage an attack in the two periods, intake/baseline and during
      and after training. Three findings are of interest. The first was the emergence
      of discriminative stimuli that because they were present when self-management
      skills were initially reinforced, altered the future probability of performance
      of the skills. Peak flow values and asthma action plans qualified as
      discriminative stimuli in that their use often prompted patients to perform steps
      to alleviate and abort episodes. Second, several processes comprise self
      management, ranging from goal setting to self-appraisal of one's actions. Self
      monitoring is the backbone of self-management. However, what emerged from the
      current study is the importance of two other processes: 1) information collection
      and processing and 2) decision making. When subjects were introduced to self
      monitoring via use of peak flow meters, an asthma diary, and a report of an
      attack, they began using these tools, often in a trial-and-error manner, to match
      the information they obtained to the actions they took. As a result, they became
      skilled at self-monitoring prior to training. During and after training, however,
      patients indicated they were skilled at processing and making decisions based on
      the data they collected. Finally, stimuli present during an attack came to prompt
      distinctive patterns whereby individual patients considered the reciprocal
      interaction of environmental, physiological, behavioral, and cognitive variables
      to control attacks. Action taken by patients reflected data processing and
      decision making on the part of patients in selecting and performing those self
      management skills they anticipated would generate the best outcomes.

PMID- 16293541
TI  - Asthma attack associated with oxidative stress by exposure to ETS and PAH.
AB  - Asthma is primarily an airways inflammatory disease, and the bronchial airways
      have been shown to be particularly susceptible to oxidant-induced tissue damage.
      OBJECTIVE: The purpose of this study was to investigate whether pulmonary
      inflammation in asthma is associated with exposure to environmental oxidants such
      as polycyclic aromatic hydrocarbon (PAH) and environmental tobacco smoke (ETS).
      METHOD: We assessed the exposure level of PAH and ETS by using urinary 1
      hydroxypyrene glucuronide (1-OHPG) and cotinine. We estimated oxidative damage
      and inflammatory cytokine levels from 16 asthma patients and 16 patients in
      stable conditions 1 to 2 months later. RESULTS: Our study showed that the levels
      of oxidative damage, as measured by malondialdehyde (MDA), were significantly
      increased (p = 0.006) during the asthma attacks. Proinflammatory and anti
      inflammatory cytokines were both increased during the asthma attacks compared to
      the stable conditions at follow-up. Interleukin (IL-6) and IL-10 were especially
      increased significantly (p = 0.015 and p < 0.001, respectively). Correlations
      were observed between inflammatory cytokines such as IL-6 and IL-1beta (p =
      0.034). CONCLUSION: This study supports the results of in vitro studies that
      oxidative stress, specifically lipid peroxidation, contributes to the
      pathophysiology of asthma. Therefore, environmental interventions based on this
      better understanding are needed to significantly reduce oxidant stress and
      prevent or minimize the development of asthmatic symptoms.

PMID- 16293542
TI  - The net cost of asthma to North Carolina Medicaid and the influence of
      comorbidities that drive asthma costs.
AB  - To determine the net direct medical cost of asthma and to investigate factors
      influencing costs, a case-control study using data from North Carolina Medicaid
      (May 1996-April 1998) was used. Comparison subjects were matched 1:1 on age,
      gender, and race. Multivariate generalized least-squares models were estimated.
      The adjusted net cost of asthma (N = 27,493) was 1250 dollars. The number of beta
      agonist and oral corticosteroid prescriptions was significantly associated with
      higher costs. The adjusted net cost of asthma to North Carolina Medicaid is
      approximately 1250 dollars, and the cost of asthma is influenced by beta-agonist
      and oral corticosteroid exposure.

PMID- 16293543
TI  - Risk factors associated with occurrence of clinical deterioration after cessation
      of beclomethasone in asthmatic children and adolescents.
AB  - Despite recent advances in the treatment of asthma using inhaled corticosteroids,
      the outcome for children after its discontinuation is not well known. This study
      aims to analyze the rate of clinical deterioration and related risk factors after
      beclomethasone withdrawal in asthmatic children and adolescents. One hundred two
      subjects with moderate or severe persistent asthma, who had started treatment
      with beclomethasone at the age of 2-11 years, were followed for 1 year after drug
      cessation. Depending on the occurrence of clinical deterioration, they were
      allocated to two groups, and then comparisons were made with respect to clinical
      criteria and skin prick test results. Statistical analysis was undertaken by
      using descriptive statistics and Cox's regression model. Treatment with
      beclomethasone had to be restarted in 28 patients (27.5%) because of relapse.
      There was a significant association with the risk of clinical deterioration with
      mother's history of asthma [hazard ratio (HR) = 2.19, 95% CI = 1.01-4.76, p =
      0.04] and father's history of asthma and/or allergic rhinitis (HR = 2.34, 95% CI
      = 1.06-5.26, p = 0.03). A period shorter than 6 months without symptoms before
      prophylaxis cessation (HR = 2.26, 95% CI = 0.98-5.26, p = 0.05) and atopy (RH =
      2.75, 95% CI = 0.94-7.69, p = 0.06) were also associated with risk of relapse but
      with marginal statistical significance. Results suggest that clinical benefits
      were maintained for at least 1 year in the majority of the children after the
      cessation of prophylaxis. Special attention must be given to those with atopy and
      a parental history of asthma and rhinitis because of the risk of clinical
      deterioration.

PMID- 16293544
TI  - Reversibility test in the early stages of bronchial asthma.
AB  - In the early stages of bronchial asthma, it is frequent to find subjects with a
      positive history and an FEV1 or FEV1/FVC > 80% of the predicted value. This study
      investigated if the test of reversibility showed a reversible airway obstruction
      (RAO) in 291 subjects with the above clinical and functional features. Forced
      expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and expiratory
      flows (PEF, MEF50, FEF(25-75)) were registered before and 20 minutes after
      salbutamol administration (200 mcg by MDI). Of 291 subjects, FEV1 increased in 73
      (25%) after bronchodilator > or = 12% compared to baseline; the number of
      subjects with a > or = 35% increase in MEF50 or FEF(25-75) were similar in terms
      of percentage (respectively, 29.2% and 29%), whereas those with increases in FVC
      (> or = 12%) and in PEF (> or = 15%) were significantly lower (respectively, 2.7%
      and 12.3%). The percentage of subjects with RAO (FEV1 increase after
      bronchodilator > or = 12%) was lower (12%) in the subgroup (108 subjects), with
      an MEF50 > or = 70% of the value predicted at the baseline assessment, and higher
      (36%) in the subjects of the subgroup (183 subjects) with an MEF50 < 70%. In
      conclusion, it is advisable to carry out reversibility tests in all subjects with
      symptoms indicative of asthma even if their functional tests are "normal" because
      in a considerable number of cases the RAO was found to confirm the suspected
      diagnosis and provided a more reliable classification of the disease.

PMID- 16293545
TI  - Influences on childhood asthma in low-income communities in China and the United
      States.
AB  - For comparison of childhood asthma, the same case-finding survey and parent
      interview questionnaires were used to collect data from 639 children with asthma
      in 21 elementary schools in Beijing and 835 children with asthma in 14 elementary
      schools in Detroit, Michigan. Asthma prevalence in Beijing (7.3%) was more than
      three times lower than in Detroit (24%) despite a high level of smoking among
      Chinese parents. Body mass index (BMI; weight in kilograms divided by height in
      meters squared) levels were higher in Detroit but were not associated with
      persistent asthma in either country. Higher levels of past infection in Beijing
      and household allergens in Detroit were noted and may be associated with
      differences in prevalence. Despite less severe disease observed in Beijing,
      hospitalizations and office visits did not differ from Detroit. This may be
      partially associated with less use of anti-inflammatory medicine and lower levels
      of parental asthma management in China.

PMID- 16293546
TI  - Translation squared: improving asthma care for high-disparity populations through
      a safety net practice-based research network.
AB  - To assess the effectiveness of an intervention designed to increase compliance
      with national asthma care guidelines in primary care safety net health centers
      serving high-disparity patient populations, we conducted a group-randomized
      controlled trial (seven intervention sites and nine control sites) in federally
      funded community health centers in eight southeastern states. There were three
      components involved in the intervention: resources (asthma kits including peak
      flow meter, MDI spacer device, plus educational materials), training of all
      health center staff in asthma care guidelines, and tools or templates for
      practice-level systems change (asthma flow sheets and standing orders). Control
      group sites received only copies of the national asthma guidelines. Chart reviews
      were performed to determine practitioner's compliance with national guidelines
      for asthma care. Clinicians practicing in intervention health centers showed
      significantly (p < 0.01) greater improvement on some measures than did the
      control health centers, although postintervention compliance with guidelines was
      still suboptimal. Disseminating national guidelines is not enough. Providing
      training and guideline-specific resources, in combination with tools for practice
      change, improved care significantly even in safety net health centers serving
      high-disparity patient populations.

PMID- 16293547
TI  - High prevalence of asthma symptoms in the Canary Islands: climatic influence?
AB  - The worldwide variation in asthma prevalence prompted us to carry out a study to
      assess the variability of asthma-related symptoms in young adults on the islands
      of Gran Canaria and Tenerife. We used the questionnaire used in the European
      Community Respiratory Health Survey with the addition of two questions on smoking
      and ancestors from the Canary Islands. In each island, this questionnaire was
      distributed to a random sample of 5000 subjects aged 20-44 years. Of the 10,000
      subjects, 9,506 (95.06%) were considered eligible. We obtained 7,132 (75.03%)
      responses. The prevalence of the different symptoms was wheezing 25.3%, nocturnal
      thoracic tightness 18.0%, awakened by an attack of shortness of breath 13.1%,
      attack of nocturnal coughing 33.3%, attack of asthma 4.3%, current asthma
      treatment 6.2%, and nasal allergies 18.0%. Women and smokers showed a
      significantly higher prevalence of asthma symptoms. No significant difference in
      symptoms was found between subjects whose ancestors were of Canarian origin and
      those with ancestors born outside the Canaries. As has been observed on other
      islands (Great Britain and New Zealand), asthma is common in individuals from 20
      to 44 years of age in the Canaries. We hypothesize that climatic conditions play
      an important role in the prevalence of asthma symptoms.

PMID- 16293548
TI  - Maternal fish consumption during pregnancy and risk of early childhood asthma.
AB  - Maternal fish consumption during pregnancy may affect children's asthma risk by
      modulating early-life immune development. Type of fish intake may be important
      because of differences in fatty acid content. To test this hypothesis, we
      conducted a nested case-control study, selecting subjects from the Children's
      Health Study, a population-based study of school-aged children in southern
      California. Cases had physician-diagnosed asthma and controls were asthma-free by
      age 5 years. Mothers or guardians provided information on fish consumption during
      pregnancy in telephone interviews. We computed odds ratio (OR) and 95% confidence
      interval (CI) by using conditional logistic regression models that accounted for
      the sampling. In children born to mothers with a history of asthma, the OR of
      asthma was 0.20 (95% CI = 0.06-0.65) when mothers ate oily fish at least monthly
      during pregnancy compared with no consumption (p(trend) = 0.006). Maternal oily
      fish consumption during pregnancy did not benefit children of non-asthmatic
      mothers. In contrast, fish stick (a source of trans-fats) consumption during
      pregnancy increased asthma risk in children (OR = 2.04; 95% CI = 1.18-3.51). Our
      results suggest that maternal oily fish intake during pregnancy may protect
      offspring from asthma; however, eating fish sticks during pregnancy may increase
      asthma risk in children.

PMID- 16293549
TI  - Lung disease and asthma severity in adults with asthma: data from the Third
      National Health and Nutrition Examination.
AB  - Risk factors for obstructive or restrictive lung disease among persons with
      asthma are not well defined. Data from the Third National Health and Nutrition
      Examination Survey were used to determine predictors of poor lung function among
      1063 adults, aged 20 years and older, who self-report physician-diagnosed asthma
      any time during their life regardless of current asthma status. Obstructive lung
      disease and restrictive lung disease were defined by using spirometry and
      modified Global Initiative for Chronic Obstructive Lung Disease criteria.
      Reported symptoms were used to grade asthma severity. Logistic regression models
      were used to examine associations between lung disease, respiratory symptom
      severity, and adults who ever had asthma. Risk factors for spirometry-defined
      obstructive lung disease included increasing age, body mass index < 18.5, current
      asthma, and non-white race (p < 0.05). Risk factors for spirometry-defined
      restrictive lung disease included older age at asthma diagnosis, low
      socioeconomic status, current asthma, and being female (p < 0.05). Risk factors
      for moderate or severe respiratory symptoms included older age at diagnosis and
      current smoking status (p < 0.05). Asthma is a known risk factor for chronic
      obstructive lung disease; these data also suggest that adults, particularly
      females, who are older at the time of asthma diagnosis, may be at risk to develop
      spirometry-defined restrictive lung disease as well. These data also suggest that
      a significant proportion of people with lifetime asthma have impaired lung
      function; however, it is unclear if more aggressive therapy for asthma would
      prevent these complications. To further examine the role of these factors in
      predicting poor lung function among adults with asthma, additional information is
      needed on these patients' asthma therapy, natural history, and environmental
      exposures.

PMID- 16293551
TI  - Spotlight on gastroenterology - the Nobel Prize Laureates in Physiology or
      Medicine 2005: John Robin Warren and Barry James Marshall.

PMID- 16293552
TI  - Cell proliferation in the gastric epithelium of the ulcer rat.
AB  - OBJECTIVE: Cell division is brisk in the ulcer margin and many of the new cells
      will migrate over and cover the ulcer bed. The aim of this study was to determine
      how agents that promote or delay gastric ulcer healing influence cell
      proliferation in the gastric epithelium. MATERIAL AND METHODS: Acetic acid ulcers
      were produced in the rat gastric corpus; non-ulcer rats served as controls. All
      rats were given a continuous infusion of (3)H-thymidine. Some rats were also
      given gastrin or indomethacin, or infected with Helicobacter pylori. The rats
      were killed after 1, 2, 6 or 13 days, and the ulcer margin and undamaged corpus
      were excised for determination of labeling index (LI) by autoradiography. Antrum,
      duodenum and colon were also studied. Silver grain counting was carried out in
      some groups. RESULTS: LI in the ulcer margin grew exponentially, reaching 84%
      after 6 days; gastrin increased, and indomethacin decreased LI significantly. In
      6-day ulcer rats that were given 3H-thymidine only during the first day LI was
      5%, while in those given 3H-thymidine only during the last day LI was 27%. LI and
      silver grain counting results indicated that during the first 6 days of healing
      the epithelial cells in the ulcer margin divide twice. In the undamaged
      epithelium of the 1-day ulcer rats LI was <one-third, and in the antral
      epithelium one-half of that in the non-ulcer controls. CONCLUSIONS: During the
      first 6 days of healing, the LI of the non-parietal epithelial cells increases
      exponentially in the ulcer margin; this is enhanced by gastrin. The unexpected
      finding in the ulcer rats of decreased LI in undamaged oxyntic and antral
      epithelium may be caused by a block of the G1 restriction point in the cell
      cycle. The reason for this remains obscure.

PMID- 16293553
TI  - Calcium channel antagonists and inhibition of human sphincter of Oddi
      contractions.
AB  - OBJECTIVE: Nifedipine has been used in the treatment of sphincter of Oddi
      dyskinesia, a biliary disease characterized by upper abdominal pains and
      increased pressure in the sphincter. The effects of other calcium channel
      antagonists on sphincter of Oddi have not been elucidated. MATERIAL AND METHODS:
      We compared the effects of three calcium blockers with differing smooth muscle
      selectivity (verapamil, nifedipine and felodipine) on human sphincter of Oddi
      contractions. Transverse sections of the sphincter obtained from five patients
      undergoing Whipple resection were studied in an organ bath chamber in vitro.
      RESULTS: All three calcium blockers significantly (>50%) inhibited the
      acetylcholine-induced and KCl-induced sphincter contractions in a dose-dependent
      manner. Both nifedipine and felodipine were more potent than verapamil in
      inhibiting the acetylcholine-induced contractions, whereas only nifedipine, but
      not felodipine, reduced the KCl-elicited contractions more than verapamil.
      CONCLUSIONS: The smooth muscle selective calcium channel antagonists are potent
      inhibitors of human sphincter of Oddi contractions. Although nifedipine is, to
      date, the only agent studied in clinical settings, other dihydropyridines are
      also likely to be useful in sphincter of Oddi dyskinesia.

PMID- 16293554
TI  - Duodenal cytotoxic lymphocytes in cow's milk protein sensitive enteropathy and
      coeliac disease.
AB  - OBJECTIVE: Pathogenetic mechanisms of cow's milk protein-sensitive enteropathy
      (CMSE) are poorly defined, but elevated serum granzyme levels and an increase in
      duodenal intraepithelial lymphocytes (IELs) expressing TIA-1 suggest the
      involvement of abnormal lymphocyte cytotoxicity. To evaluate cytotoxicity in CMSE
      we analysed the expression of cytotoxic granule components in duodenal IELs. For
      comparison, we studied subjects with coeliac disease (CD), in which lymphocyte
      cytotoxicity is pathogenically important. MATERIAL AND METHODS: Fifty-four
      children were examined by endoscopy for gastrointestinal complaints. Twenty-one
      subjects had a final diagnosis of CMSE, 15 children had untreated CD and 18
      controls showed no definite gastrointestinal disease. Mucosal samples furnished
      from the bulb and descending duodenum were stained for CD3, perforin, granzymes A
      and B and TIA-1. RESULTS: In both CMSE and CD, increase of mid-duodenal TIA-1,
      perforin and granzyme A expressing IELs was seen, the counts in CD being much
      higher, and increased expression was also seen in the bulb. Granzyme B expression
      was increased only in CD. In CMSE, no evidence of villous atrophy was seen.
      CONCLUSIONS: Increase in duodenal IELs expressing cytotoxic granules is a
      characteristic feature in CMSE, although to a lesser degree than in CD.
      Cytotoxicity is suggested to be involved in the pathogenesis of intestinal
      dysfunction in CMSE, but based on the absence of villous abnormalities may not be
      mainly targeted to enterocytes. The mechanisms leading to the accumulation of
      these cells in CMSE need further investigation.

PMID- 16293555
TI  - Undiagnosed silent coeliac disease: a risk for underachievement?
AB  - OBJECTIVE: Silent coeliac disease is reported in 1% of Caucasian populations, but
      there is a lack of knowledge of its natural course and the risk of complications.
      The need for population screening is debated. We sought for complications of
      untreated coeliac disease in a well-defined cohort of Finnish adults. MATERIAL
      AND METHODS: Subjects (n=2427, ages 24-39 years) attending the 21-year follow-up
      visit of the study "Cardiovascular Risk in Young Finns" completed an extensive
      questionnaire on their health, diet, social situation and family life, and were
      given a medical examination. Measurement of serum IgA-transglutaminase and IgA
      endomysium antibodies identified 21 subjects with silent coeliac disease.
      RESULTS: The subjects with silent coeliac disease did not differ from the rest of
      the cohort in age, gender, stature, weight, medical diagnoses (autoimmune,
      malignant), health concerns, use of alternative medications, physical activity,
      or in the cause of death their parents. They had lower serum HDL-cholesterol
      (1.12 versus 1.29 mmol/L; p=0.015), as described for active coeliac disease.
      Fewer (5.3% versus 22.8%; p=0.047) had a university or college degree or worked
      in managerial or professional positions (28% versus 45%; p=0.112). CONCLUSIONS:
      The underachievement in education and working life observed in subjects with
      silent coeliac disease is a new and intriguing finding and may be related to the
      increased prevalence of depressive and disruptive behavioural disorders described
      in teenagers with untreated coeliac disease. Our findings add a new ingredient to
      the ongoing discussion regarding the need for population screening for silent
      coeliac disease.

PMID- 16293556
TI  - Metalloelastase (MMP-12) is upregulated in the gut of pediatric patients with
      potential celiac disease and in type 1 diabetes.
AB  - OBJECTIVE: A slight to moderate increase in autoantibodies to transglutaminase 2
      (TG2), but no morphological evidence of villous atrophy to confirm the diagnosis
      of celiac disease (CD) poses a challenge for clinicians. Our aim was to study the
      matrix metalloproteinase (MMP) profile, proliferative and apoptotic
      characteristics of jejunal biopsies obtained from such pediatric patients in
      order to find markers predictive of early changes in extracellular matrix
      degrading enzymes in the development of CD. MATERIAL AND METHODS: Twenty-eight
      children with positive screening tests (increase in transglutaminase and/or
      endomysium antibodies), but minor histological changes in the gut (Marsh grade 0
      2), were studied and followed up for 2-3 years. In situ hybridizations for MMP-1,
      -3 and -12 were performed and sections were immunostained for MMP-19 and -26.
      Proliferating cells were identified by Ki-67 immunostaining and apoptotic cells
      using the TUNEL technique. RESULTS: MMP-12 was detected in macrophages in 16/28
      samples and its expression was associated with increased autoantibodies for TG2
      and densities of CD3 and gammadelta positive T-cells in the epithelium. The
      number of stromal MMP-26 positive cells was high in patients with high TG2
      titers. Expression of MMP-12, MMP-1 and -3 clustered in children with type 1
      diabetes (T1D) and the proportion of apoptotic mucosal cells was increased in
      patients with T1D compared to the others. When children with CD were compared to
      those who did not develop it, the numbers of IEL, cryptal Ki-67, CD-3, and MMP-12
      positive cells were higher and showed the most significant differences.
      CONCLUSIONS: In pediatric patients, increased numbers of MMP-12 positive
      macrophages in lamina propria associate with high titers of antibodies to TG2 and
      proness to CD. A stage of mild inflammation may contribute to the upregulation of
      MMPs in the gut of patients with T1D.

PMID- 16293557
TI  - Estrogenic regulation of cholesterol biosynthesis and cell growth in DLD-1 human
      colon cancer cells.
AB  - OBJECTIVE: The main molecules of cholesterol homeostasis are 3-hydroxy-3
      methylglutaryl-coenzyme A reductase (HMG-CoAR), the key enzyme of the
      biosynthetic pathway, and the low-density lipoprotein receptor (LDL-R), which is
      responsible for the uptake of plasma lipoproteins. The increase in the endogenous
      cholesterol biosynthesis results in stimulation of DNA synthesis, while the
      inhibition of cholesterogenesis suppresses cell growth. Estrogens have been
      reported to regulate hepatic LDL-R expression and modulate cell proliferation in
      different tissues. In order to clarify the mechanisms of estrogenic growth
      control in colorectal carcinoma, we have investigated the effects of 17beta
      estradiol exposure on LDL-R gene expression and its protein, as well as on HMG
      CoAR gene expression, its protein as well as enzyme activity in the DLD-1 human
      colon cancer cell line. The effect of 17beta-estradiol on both cell growth and
      apoptosis in this cell line was also investigated. MATERIAL AND METHODS: LDL-R
      and HMG-CoAR gene expressions were determined using quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) in DLD-1 cells at different
      times and doses of 17beta-estradiol exposure. LDL-R and HMG-CoAR protein
      expression was detected by Western immunoblotting. HMG-CoAR activity was
      evaluated using a radiometric assay. Cell proliferation was measured by
      colorimetric MTT test and incorporation of [3H]-thymidine in DNA. Apoptotic death
      was estimated by DNA fragmentation analysis. RESULTS: Estrogens induced an early
      increase of LDL-R, at both mRNA and protein level, and later decreased HMG-CoAR
      activity and protein expression. DLD-1 cells treated with 17beta-estradiol
      exhibited inhibition of DNA synthesis and apoptosis. CONCLUSIONS: The results of
      this study suggest that estrogens regulate LDL-R and HMG-CoAR and influence cell
      growth and apoptosis in colon cancer cells.

PMID- 16293558
TI  - Characteristics, prognosis and outcome of patients with oesophageal varices in a
      university hospital in Sweden 1994-1999.
AB  - OBJECTIVE: Patients with liver cirrhosis, portal hypertension and oesophageal
      varices are known to have high morbidity and mortality. The knowledge of
      incidence, aetiology and outcome in Sweden in recent years is limited. MATERIAL
      AND METHODS: All patients with oesophageal varices diagnosed for the first time
      at Sahlgrenska University Hospital during the 6-year period 1994-1999 were
      retrospectively studied. Information about the aetiology of liver cirrhosis and
      oesophageal varices, as well as about the proportion of bleeding and non-bleeding
      varices, endoscopic and pharmacological treatment and outcome, was analyszed.
      RESULTS: 312 patients were retrieved, 297 with liver cirrhosis (197 diagnosed
      before first bleeding (P), 92 after bleeding (B) and 8 at autopsy) and 15 with
      portal vein thrombosis without cirrhosis. Fifty-four percent had alcoholic liver
      disease. Fifty-five percent in group B and 13% in group P had at least one
      bleeding episode during follow-up (p<0.001). There was no significant difference
      in survival between groups B and P. Twenty-six percent of the cirrhotics died of
      liver failure and 19% from variceal bleeding. In a multivariate analysis,
      variables predicting mortality were: Child-Pugh class, group B, age and bilirubin
      levels. CONCLUSIONS: Variceal bleeding is still a strong risk factor for
      recurrent bleeding, but few die from their first bleeding. This concurs with
      studies indicating declining mortality from variceal bleeding. However, this
      patient group still has a high mortality from other causes.

PMID- 16293559
TI  - Abnormal glucose tolerance is a predictor of steatohepatitis and fibrosis in
      patients with non-alcoholic fatty liver disease.
AB  - OBJECTIVE: The majority of patients with non-alcoholic fatty liver disease
      (NAFLD) have simple steatosis. A minority, however, present with non-alcoholic
      steatohepatitis (NASH), a condition that can lead to advanced fibrosis and
      cirrhosis. The frequencies of NASH and fibrosis among patients with NAFLD and
      sustained elevation of liver function tests (LFT) are uncertain. Our aim was to
      estimate these frequencies. We characterize a population with NAFLD, with special
      emphasis on insulin resistance and the metabolic syndrome, and study possible
      predictors for different stages of the disease. MATERIAL AND METHODS: All
      referred patients with sustained elevation of LFT, radiological evidence or
      clinical suspicion of fatty liver, and absence of other liver disease, were
      invited to participate in our study in the period June 2002 to December 2004.
      RESULTS: Of 129 patients who met the inclusion criteria, 88 underwent liver
      biopsy. NAFLD was verified in 83 of them. Among these patients, 59 (71%) had the
      metabolic syndrome, 41 (49%) had NASH and 36 (43%) had fibrosis. Abnormal glucose
      tolerance (T2DM or impaired glucose tolerance) was the only independent risk
      factor for NASH (OR: 3.14; 95% CI: 1.20-8.23). Independent predictors for
      fibrosis were abnormal glucose tolerance (OR: 3.83; 95% CI: 1.29-11.40) and body
      mass index (OR: 1.20; 95% CI: 1.06-1.36) per kg/m2. CONCLUSIONS: Both NASH and
      fibrosis are frequently present among patients with NAFLD and sustained elevation
      of LFT. The probability of these potentially progressive stages of NAFLD
      increases with the presence of abnormal glucose tolerance.

PMID- 16293560
TI  - Cholecystectomy in Sweden 1987-99: a nationwide study of mortality and
      preoperative admissions.
AB  - OBJECTIVE: Information on mortality after cholecystectomy in defined populations
      is limited. In this study we examined the case fatality rates and mortality
      ratios, based on register data. MATERIAL AND METHODS: Hospital discharge and
      death certificate data were linked for all patients undergoing cholecystectomy in
      Sweden in 1987-99. Mortality risk was calculated as the standardized mortality
      ratio (SMR). RESULTS: From 1 January 1987 to 1 December 1999, 123,099 patients
      underwent cholecystectomy for acute or chronic gallbladder disease. Between 1987
      91 and 1995-99, the incidence of cholecystectomy increased by 13%, median age of
      patients decreased and the proportion of women increased. From 1995 to 1999, 32%
      of all cholecystectomies were completed as open cholecystectomy. During this
      period, 82% of patients aged 70 years or older with acute gallstone disease had
      an open cholecystectomy. For patients with chronic gallstone disease, the
      proportion was 43%. Postoperative crude mortality within 30 days for all patients
      was 0.4%. Patients with acalculous gallbladder disease had double the mortality
      risk compared with patients with calculous disease, and patients with acute
      cholecystitis had double the risk compared with patients with chronic disease.
      High age, previous hospital admission for conditions other than gallbladder
      disease, and cholecystectomy completed as an open procedure increased the risk,
      whereas gender and calendar year did not significantly affect the mortality risk.
      Biliary tract diseases accounted for 61% of all postoperative deaths, whereas 26%
      were due to cardiovascular diseases. CONCLUSIONS: During the 1990s,
      cholecystectomy incidence increased, whereas postoperative mortality risk
      remained unchanged. In order to further reduce the mortality risk, particular
      attention should be paid to elderly and frail patients and to patients with
      acalculous gallbladder disease.

PMID- 16293561
TI  - Gemcitabine treatment in patients with inoperable locally advanced/metastatic
      pancreatic cancer and prognostic factors.
AB  - OBJECTIVE: Most patients with pancreatic cancer show an inoperable locally
      advanced/ metastatic tumour at the time of diagnosis. The present study was aimed
      at determining the prognostic factors in patients with advanced pancreatic
      carcinoma treated with gemcitabine. MATERIAL AND METHODS: Sixty-seven
      unresectable or metastatic pancreatic cancer patients treated with gemcitabine
      were included in the study and a total of 258 cycles of treatment were applied.
      RESULTS: The overall response rate was 5%. Thirty-one percent of the patients had
      stable disease, whereas progressive disease was seen in 49%. Clinical benefit
      response rate was 15%. The median duration of response was 7.3 months. Median
      progression-free survival was 3 months, while median overall survival was 9
      months. Univariate analysis revealed that worse results were found in patients
      with performance status (PS) = 2, and in patients with primary tumour location in
      the body or tail of the pancreas (p<0.05). Multivariate analysis of data revealed
      that the most important factor was PS of the patient, as the patients with PS = 2
      had worse results than the patients with PS = 0-1 (p<0.05). CONCLUSIONS: Low PS
      is a negative predictive factor for the survival of patients with advanced
      pancreatic carcinoma treated with gemcitabine.

PMID- 16293562
TI  - Fecal pyruvate kinase (M2-PK): a new predictor for inflammation and severity of
      pouchitis.

PMID- 16293563
TI  - Elementary diet reduces diarrhoea associated with microscopic colitis.

PMID- 16293564
TI  - Clinical and diagnostic aspects of cystic insulinoma.
AB  - Cystic endocrine tumors of the pancreas rarely occur, and only a few cases of
      cystic insulinoma have been reported to date. Diagnosis of insulinoma could be
      difficult if the functional activity is incomplete, possibly leading to blunted
      symptoms of hypoglycemia and failure in the laboratory to provide evidence of
      hyperinsulinemia. We report a clinical case of cystic insulinoma confirmed by
      histological examination after surgery, characterized by a high intracystic
      insulin concentration despite normal blood basal levels of the hormone. New
      diagnostic findings from dynamic tests and cystic fluid examination have been
      carefully focused on.

PMID- 16293565
TI  - Polypoid pleomorphic sarcoma of the colon.
AB  - In contrast to common colonic epithelial neoplasms, polypoid mesenchymal tumors
      of the colon are extremely rare. The majority of uncommon gastrointestinal
      mesenchymal tumors are associated with the so-called gastrointestinal stromal
      tumors (GIST). We present a case of a rare colonic pleomorphic sarcoma,
      macroscopically mimicking a common epithelial colonic polyp, which did not match
      the criteria of GIST. In this case report we discuss the clinical and
      pathological characteristics of a rare polypoid-shaped, pleomorphic colonic
      sarcoma and refer a mark-off to other rare mesenchymal neoplasms of the gut.

PMID- 16293566
TI  - Frontal lobe dysfunction and false memory susceptibility in older adults.
AB  - The study reported here was conducted to examine the role of frontal lobe
      function in false memory susceptibility in older adults, as little research has
      specifically examined this question in older adults. False recognition was
      compared in three groups of older adults (one with no evidence of cognitive
      impairment, one with evident frontal impairment but no other dysfunction, and an
      Alzheimer's dementia group) to a single group of young adults. Results indicate
      that false memory susceptibility was highest in the frontally impaired group,
      with young and older control participants performing similarly. In contrast,
      Alzheimer's dementia patients showed relatively low levels of false memory
      susceptibility, likely due to overall poor memory for list items, indicating that
      general memory impairments are not likely to be driving false memory
      susceptibility. Potential mechanisms underlying these effects are discussed.

PMID- 16293567
TI  - Memories of an emotional and a nonemotional event: effects of aging and delay
      interval.
AB  - The present study compared the memory of young and older adults for details
      pertaining to two public events of close temporal proximity but varying emotional
      import-the Columbia shuttle explosion and the 2003 Super Bowl. Participants
      responded to surveys sent within 2 weeks of these events and then again 7 months
      later, providing information about event-related details (i.e., of the events
      themselves) and personal details (i.e., of the reception event). Both age groups
      rated the shuttle tragedy as significantly more emotional than the Super Bowl,
      and although older adults often had poorer memory overall, both age groups
      remembered more about the shuttle than they did about the Super Bowl. Further,
      the age discrepancy (young adults remembering more than older adults) was less
      pronounced for the shuttle than for the Super Bowl. Thus, older adults' memories
      appear to benefit from the emotional salience of real-life events.

PMID- 16293568
TI  - Angiotensin II stimulates endothelial integrin beta3 expression via nuclear
      factor-kappaB activation.
AB  - The present study examined the effect and part mechanism of angiotensin II
      stimulated integrin beta3 gene expression in human umbilical vein endothelial
      cells. Protein level and mRNA level of integrin beta3 expression were determined
      using enzyme-linked immunoadsorbent assay and reverse transcription-polymerase
      chain reaction. Four plasmids of 5'-different deletion of integrin beta3 gene
      promoter were constructed to transiently transfected into cells to uncover the
      region in response to angiotensin II. Blockade of nuclear factor-kappaB (NF
      kappaB) signaling pathway effect on integrin beta3 expression was analyzed by
      cotransfection with mutant plasmids for NF-kappaB-inducing kinase, inhibitory
      proteins alpha and beta of NF-kappaB kinase, respectively, together with the
      integrin beta3 plasmid including the sequence -1486 approximately - 900. The
      study found that 10(-8) mol/L,10(-7) mol/L, 10(-6) mol/L, and 10(-5) mol/L
      angiotensin II increased integrin beta(3) protein level by 45%, 52%, 62%, and 73%
      respectively. Angiotensin II at 10(-6) mol/L increased integrin beta3 mRNA level
      by 67%. The luciferase activity of the integrin beta3 plasmid PGL3 - 1486
      approximately - 900 increased by 84.72% in response to angiotensin II. N
      acetylcysteine blocked angiotensin II-induced NF-kappaB activity and integrin
      beta3 expression. Blockade of NF-kappaB signaling pathway abolished the
      stimulation of angiotensin II. These results suggest that angiotensin II
      stimulates integrin beta3 expression partly by NF-kappaB activation.

PMID- 16293569
TI  - The effects of aging on the recognition of different types of associations.
AB  - The present study examined how aging influences item and associative recognition
      memory, and compared memory for two types of associations: associations between
      the same kinds of information and associations between different kinds of
      information. A group of young adults and a group of older adults performed a
      forced-choice face recognition task and two multitrial forced-choice associative
      recognition tasks, assessing memory for face-face and face-spatial location
      associations. The results showed disproportionate age-related decline of
      associative recognition compared to intact item recognition. Moreover, aging
      affected both types of associative tasks in the same way. The findings support an
      associative deficit hypothesis (Naveh-Benjamin, Journal of Experimental
      Psychology: Learning, Memory and Cognition, 26, 1170-1187, 2000), which
      attributes a substantial part of the age effect on episodic memory tasks to
      difficulty with binding individual components into a cohesive memory trace. This
      associative deficit seems to affect same-information associations, as well as
      different-information associations.

PMID- 16293571
TI  - A comparison of narratives told by younger and older adults.
AB  - The few studies that have examined verbal discourse in both young and older
      adults have yielded inconsistent results with respect to talkativeness and story
      quality. The disparity may arise from methodological differences. In this study
      the authors examined word count, irrelevant utterances, and ratings of quality of
      stories told by 24 young (mean age = 19.21) and 24 old (mean age = 72.13) adults.
      The authors found minimal age differences. A separate sample of 10 young and 10
      older adults of ages similar to those of the storytellers read and rated all the
      stories. Raters were highly variable in their subjective evaluations of story
      quality, although satisfactory generalizability coefficients can be achieved with
      a sufficiently large number of raters. Most studies of discourse quality,
      however, use few raters, which produces unreliable measurement that can
      contribute to the inconsistent results reported in the literature.

PMID- 16293570
TI  - Congruence of medication information from a brown bag data collection and
      pharmacy records: findings from the Seattle longitudinal study.
AB  - The validity of health information obtained through participants' reports of
      current medications (e.g., the brown bag method) is an important, but under
      studied, area. In the current study, we examined the congruence of medication
      reports from a brown bag data collection with the pharmacy prescription records
      for 1430 participants (ages 23 to 97 years) of the seventh wave of the Seattle
      Longitudinal Study. Overall, the congruence of the brown bag data and pharmacy
      records was high. Congruence was better for younger participants, healthier
      participants, and for medications taken for serious conditions or on a regular
      basis. When the focus is on assessing participants' medications at a specific
      point in time (e.g., on the day of testing), brown bag data may provide more
      complete information than pharmacy records. Age and health status of the
      participants as well as the type of medications of interest should be considered
      when determining the validity of medication information reported by participants.

PMID- 16293572
TI  - Reduction of Caenorhabditis elegans frataxin increases sensitivity to oxidative
      stress, reduces lifespan, and causes lethality in a mitochondrial complex II
      mutant.
AB  - Friedreich ataxia is an autosomal recessive neurological disorder caused by
      deficiency of the mitochondrial protein frataxin. Studies in patient cells, mouse
      knockout animals, and Saccharomyces cerevisiae models have suggested several
      hypotheses on the frataxin function, but the full physiology of frataxin in
      mitochondria has not been well established yet. We have characterized the genomic
      structure of frh-1, the Caenorhabditis elegans frataxin gene, and we have
      developed a transient knockdown model of C. elegans frataxin deficiency by RNA
      interference. frh-1(RNAi) worms show a consistent pleiotropic phenotype that
      includes slow growth, lethargic behavior, egg laying defects, reduced brood size,
      abnormal pharyngeal pumping, and altered defecation. Lifespan is significantly
      reduced, and worms have increased sensitivity to oxidative stress that, in turn,
      might explain the reduction of longevity of the worms. We also demonstrate
      synthetic genetic interaction between frh-1 and mev-1, the gene encoding the
      succinate dehydrogenase cytochrome b subunit of complex II in mitochondria,
      suggesting a possible role of the C. elegans frataxin in the electron transport
      chain; thus, the respiratory chain might be involved in the pathogenesis of the
      disease. We propose that this C. elegans model may be a useful biological tool
      for drug screening in Friedreich ataxia.

PMID- 16293573
TI  - Sperm ion channels: molecular targets for the next generation of contraceptive
      medicines?

PMID- 16293574
TI  - A three-dimensional model to study the epigenetic effects induced by the
      microenvironment of human embryonic stem cells.
AB  - New methods of study are necessary to define the homeostatic mechanisms that
      regulate stem cell properties and to determine the possible epigenetic influence
      of the stem cell microenvironment on the phenotype of tumor cells. We recently
      demonstrated that the tumorgenicity of aggressive cutaneous melanoma cells can be
      abrogated by the zebrafish embryonic microenvironment. We have developed a three
      dimensional (3D) model, as a corollary of these findings, that allows melanoma
      cells to be exposed to the microenvironment of human embryonic stem cells
      (hESCs). Using this methodology, we determined that hESC microenvironments can
      dramatically influence the behavior of aggressive melanoma cells. Specifically,
      exposure of tumor cells to H1- or HSF-6-hESC matrices induced a melanocyte-like
      phenotype with the ability to form colonies similar to hESCs. Furthermore,
      melanoma cells were less invasive after culture on hESC microenvironments. These
      findings demonstrate the utility of this 3D model for studying the unique factors
      deposited by hESCs and for investigating the epigenetic effects that stem cell
      microenvironments may have on tumor progression.

PMID- 16293575
TI  - Rapid generation of stable transgenic embryonic stem cell lines using modular
      lentivectors.
AB  - Generation of stable transgenic embryonic stem (ES) cell lines by classic
      transfection is still a difficult task, requiring time-consuming clonal
      selection, and hampered by clonal artifacts and gene silencing. Here we describe
      a novel system that allows construction of lentivectors and generation of stable
      ES cell lines with > 99% transgene expression within a very short time frame.
      Rapid insertion of promoters and genes of interest is obtained through a modular
      recombinational cloning system. Vectors contain central polypurine tract from HIV
      1 element and woodchuck hepatitis virus post-transcriptional regulatory element
      as well as antibiotic resistance to achieve optimal and homogenous transgene
      expression. We show that the system 1) is functional in mouse and human ES cells,
      2) allows the generation of ES cells expressing genes of interest under the
      control of ubiquitous or tissue-specific promoters, and 3) allows ES cells
      expressing two constructs through selection with different antibiotics to be
      obtained. The technology described herein should become a useful tool in stem
      cell research.

PMID- 16293577
TI  - Identification of a primitive brain-derived neural stem cell population based on
      aldehyde dehydrogenase activity.
AB  - Stem cells are undifferentiated cells defined by their ability to self-renew and
      differentiate to progenitors and terminally differentiated cells. Stem cells have
      been isolated from almost all tissues, and an emerging idea is that they share
      common characteristics such as the presence of ATP-binding cassette transporter
      G2 and high telomerase and aldehyde dehydrogenase (ALDH) activity, raising the
      hypothesis of a set of universal stem cell markers. In the present study, we
      describe the isolation of primitive neural stem cells (NSCs) from adult and
      embryonic murine neurospheres and dissociated tissue, based on the expression of
      high levels of ALDH activity. Single-cell suspension was stained with a
      fluorescent ALDH substrate termed Aldefluor and then analyzed by flow cytometry.
      A population of cells with low side scatter (SSC(lo)) and bright ALDH (ALDH(br))
      activity was isolated. SSC(lo)ALDH(br) cells are capable of self-renewal and are
      able to generate new neurospheres and neuroepithelial stem-like cells.
      Furthermore, these cells are multipotent, differentiating both in neurons and
      macroglia, as determined by immunocytochemistry and real-time reverse
      transcription-polymerase chain reaction analysis. To evaluate the engraftment
      potential of SSC(lo)ALDH(br) cells in vivo, we transplanted them into mouse
      brain. Donor-derived neurons with mature morphology were detected in the cortex
      and subcortical areas, demonstrating the capacity of this cell population to
      differentiate appropriately in vivo. The ALDH expression assay is an effective
      method for direct identification of NSCs, and improvement of the stem cell
      isolation protocol may be useful in the development of a cell-mediated
      therapeutic strategy for neurodegenerative diseases.

PMID- 16293576
TI  - A crosstalk between myeloma cells and marrow stromal cells stimulates production
      of DKK1 and interleukin-6: a potential role in the development of lytic bone
      disease and tumor progression in multiple myeloma.
AB  - Multiple myeloma (MM) is a malignancy of antibody-secreting plasma cells. B-cell
      plasmacytomas stimulate bone resorption and angiogenesis, resulting in osteolytic
      lesions in the skeleton which persist upon successful treatment of the malignancy
      with chemotherapy. We found that an interaction between MM cells and mesenchymal
      stem cells (MSCs) from bone marrow stroma results in the formation and
      persistence of osteolytic bone lesions. It is known that MM cells activate
      osteoclast activity and secrete high levels of the Wnt inhibitor, Dickkopf-1,
      which prevents MSCs from differentiating into osteoblasts. We show that the Wnt
      signaling activator 6-bromoindirubin-3'-monoxime (BIO) releases MSCs from the
      osteoinhibitory effects of Dickkopf-1, whereas LiCl treatment does not.
      Additionally, we show that the >5-kDa fraction of MSC-conditioned medium promotes
      the proliferation of Dickkopf-1-secreting MM cells and that an interleukin-6 (IL
      6)-neutralizing antibody blocks this effect. IL-6 expression levels were higher
      in undifferentiated MSCs than in MSCs treated with osteogenic medium, remained
      high in the presence of Dkk1, and were reduced by BIO treatment. Therefore, BIO
      treatment reduces the MSC-stimulated proliferation of MM cells and may enable
      MSCs to repair existing osteolytic lesions.

PMID- 16293579
TI  - Characterization of a new NIH-registered variant human embryonic stem cell line,
      BG01V: a tool for human embryonic stem cell research.
AB  - Human embryonic stem cells (hESCs) offer a renewable source of a wide range of
      cell types for use in research and cell-based therapies. Characterizing these
      cells provides important information about their current state and affords
      relevant details for subsequent manipulations. For example, identifying genes
      expressed during culture, as well as their temporal expression order after
      passaging and conditions influencing the formation of all three germ layers may
      be helpful for the production of functional beta islet cells used in treating
      type I diabetes. Although several hESC lines have demonstrated karyotypic
      instability during extended time in culture, select variant lines exhibit
      characteristics similar to their normal parental lines. Such variant lines may be
      excellent tools and abundant sources of cells for pilot studies and in vitro
      differentiation research in which chromosome number is not a concern, similar to
      the role currently played by embryonal carcinoma cell lines. It is crucial that
      the cells be surveyed at a genetic and proteomic level during extensive
      propagation, expansion, and manipulation in vitro. Here we describe a
      comprehensive characterization of the variant hESC line BG01V, which was derived
      from the karyotypically normal, parental hESC line BG01. Our characterization
      process employs cytogenetic analysis, short tandem repeat and HLA typing,
      mitochondrial DNA sequencing, gene expression analysis using quantitative reverse
      transcription-polymerase chain reaction and microarray, assessment of telomerase
      activity, methylation analysis, and immunophenotyping and teratoma formation, in
      addition to screening for bacterial, fungal, mycoplasma, and human pathogen
      contamination.

PMID- 16293580
TI  - Translational research: toward better characterization of human embryonic stem
      cell lines.

PMID- 16293578
TI  - Assessing self-renewal and differentiation in human embryonic stem cell lines.
AB  - Like other cell populations, undifferentiated human embryonic stem cells (hESCs)
      express a characteristic set of proteins and mRNA that is unique to the cells
      regardless of culture conditions, number of passages, and methods of propagation.
      We sought to identify a small set of markers that would serve as a reliable
      indicator of the balance of undifferentiated and differentiated cells in hESC
      populations. Markers of undifferentiated cells should be rapidly downregulated as
      the cells differentiate to form embryoid bodies (EBs), whereas markers that are
      absent or low during the undifferentiated state but that are induced as hESCs
      differentiate could be used to assess the presence of differentiated cells in the
      cultures. In this paper, we describe a list of markers that reliably distinguish
      undifferentiated and differentiated cells. An initial list of approximately 150
      genes was generated by scanning published massively parallel signature
      sequencing, expressed sequence tag scan, and microarray datasets. From this list,
      a subset of 109 genes was selected that included 55 candidate markers of
      undifferentiated cells, 46 markers of hESC derivatives, four germ cell markers,
      and four trophoblast markers. Expression of these candidate marker genes was
      analyzed in undifferentiated hESCs and differentiating EB populations in four
      different lines by immunocytochemistry, reverse transcription-polymer-ase chain
      reaction (RT-PCR), microarray analysis, and quantitative RT-PCR (qPCR). We show
      that qPCR, with as few as 12 selected genes, can reliably distinguish
      differentiated cells from undifferentiated hESC populations.

PMID- 16293581
TI  - A new era in the ethics of human embryonic stem cell research.
AB  - Scientific progress in human embryonic stem cell (hESC) research and increased
      funding make it imperative to look ahead to the ethical issues generated by the
      expected use of hESCs for transplantation. Several issues should be addressed
      now, even though phase I clinical trials of hESC transplantation are still in the
      future. To minimize the risk of hESC transplantation, donors of materials used to
      derive hESC lines will need to be recontacted to update their medical history and
      screening. Because of privacy concerns, such recontact needs to be discussed and
      agreed to at the time of donation, before new hESC lines are derived. Informed
      consent for phase I clinical trials of hESC transplantation also raises ethical
      concerns. In previous phase I trials of highly innovative interventions,
      allegations that trial participants had not really understood the risk and
      benefits caused delays in subsequent trials. Thus, researchers should consider
      what information needs to be discussed during the consent process for hESC
      clinical trials and how to verify that participants have a realistic
      understanding of the study. Lack of attention to the special ethical concerns
      raised by clinical trials of hESC transplantation and their implications for the
      derivation of new hESC lines may undermine or delay progress toward stem cell
      therapies.

PMID- 16293582
TI  - Biodegradable polymer composite grafts promote the survival and differentiation
      of retinal progenitor cells.
AB  - Retinal progenitor cells (RPCs) are multipotent central nervous system precursors
      that give rise to all of the cell types of the retina during development. Several
      groups have reported that mammalian RPCs can be isolated and expanded in culture
      and can differentiate into retinal neurons upon grafting to the mature, diseased
      eye. However, cell delivery and survival remain formidable obstacles to
      application of RPCs in a clinical setting. Because biodegradable
      polymer/progenitor constructs have been shown to be capable of tissue generation
      in other compartments, we evaluated the survival, migration, and differentiation
      of RPCs delivered on PLLA/PLGA polymer substrates to the mouse subretinal space
      and compared these results to conventional injections of RPCs. Polymer composite
      grafts resulted in a near 10-fold increase in the number of surviving cells after
      4 weeks, with a 16-fold increase in cell delivery. Grafted RPCs migrated into the
      host retina and expressed the mature markers neurofilament-200, glial fibrillary
      acidic protein, protein kinase C-alpha, recoverin, and rhodopsin. We conclude
      that biodegradable polymer/progenitor cell composite grafts provide an effective
      means of increasing progenitor cell survival and overall yield when transplanting
      to sites within the central nervous system such as the retina.

PMID- 16293583
TI  - Endowing human adenovirus serotype 5 vectors with fiber domains of species B
      greatly enhances gene transfer into human mesenchymal stem cells.
AB  - Bone marrow-derived human mesenchymal stem cells (hMSCs) lack the Coxsackie
      adenovirus (Ad) receptor and thus are poorly transduced by vectors based on human
      Ad serotype 5 (Ad5). We investigated whether this problem could be overcome by
      using tropism-modified Ad5 vectors carrying fiber shaft domains and knobs of
      different human species B Ads (Ad5FBs). To allow quantitative analyses, these
      vectors coded for the enhanced green fluorescent protein (eGFP). Transgene
      expression analysis showed superior transduction of hMSCs by all Ad5FBs tested as
      compared with conventional Ad5 vectors. This was evident both by the frequency of
      eGFP-positive cells and by the eGFP level per cell. Highly efficient transduction
      of hMSCs, with limited variability between cells from different donors, was
      achieved with vectors displaying fiber domains of Ad serotypes 50, 35, and 16.
      These findings could not be reconciled with the very low levels of CD46, a
      recently identified receptor for species B Ads, on hMSCs, suggesting that AdFBs
      probably use receptors other than CD46 to enter these cells. We further observed
      that high eGFP levels were maintained in replication-restricted hMSCs for more
      than 30 days. In dividing hMSCs, foreign DNA delivered by Ad5FBs was expressed in
      a large fraction of the cells for approximately 3 weeks without compromising
      their replication capacity. Importantly, the transduced hMSCs retained their
      capacity to differentiate into adipocytes and osteoblasts when exposed to the
      appropriate stimuli.

PMID- 16293585
TI  - A switch in time saves mind.

PMID- 16293584
TI  - Murine bone marrow stromal cells sustain in vivo the survival of hematopoietic
      stem cells and the granulopoietic differentiation of more mature progenitors.
AB  - The study of the human hematopoietic system would be facilitated by availability
      of a relevant animal model. Because the medullar microenvironment is made of
      different types of cells, interactions between hematopoietic cells and stromal
      cells are difficult to analyze in detail. As an approach for establishing an in
      vivo model to dissect these interactions, we grafted murine bone marrow
      fibroblastic cells (MS-5 cell line) with hematopoietic cells into the kidney
      capsule of syngenic mice. To identify the origin of cells present in the graft,
      we used green fluorescent protein-stable transfected MS-5 cells for the
      transplantation. To analyze the evolution of stromal cells and identify
      hematopoietic cells able to develop in these conditions, we performed morphology,
      histochemistry, and immunohistology on tissue sections at different times after
      transplantation. When injected alone, MS-5 cells differentiate into adipocytes.
      When injected with a bone marrow suspension or with isolated CD45+ cells
      (leukocytes), the stromal cells keep their fibroblastic morphology and their
      alkaline phosphatase expression and sustain granulopoiesis. When injected with
      hematopoietic stem cells called c-kit+ Sca-1+ Lin- suspension, clusters of
      hematopoietic cells are also observed: They do not present any granulopoietic
      activity and do not belong to B or T population nor to erythroid lineage. They
      are quiescent, induce bone marrow recovery and survival of lethally irradiated
      recipients, are able to form macroscopic colonies in the spleen, and are able to
      form very few colonies in vitro, suggesting that they are hematopoietic stem
      cells. In conclusion, our results show that reticular fibroblastic stromal cells
      MS-5 sustain the survival of stem cells and are not able to induce their
      differentiation. However, they can control differentiation, proliferation, and/or
      survival of hematopoietic cells engaged in myeloid lineage.

PMID- 16293586
TI  - Immune shaping and the development of Alzheimer's disease vaccines.
AB  - Given the emotional, social, and financial devastation wrought by Alzheimer's
      disease (AD), it is imperative that effective therapeutics be devised to
      ameliorate this presently incurable disorder. Vaccine-based approaches have been
      developed to target and eliminate amyloid beta (Abeta), a key peptide implicated
      in AD pathogenesis. Preclinical successes in AD mouse models created excitement
      and impetus for the clinical application of an Abeta-based vaccine. Eliciting
      immune responses against a self-peptide (that is, a peptide produced by the
      organism itself), such as Abeta, carries with it the potential to induce
      autoimmune and inflammatory conditions in the vaccinated individual, a caveat
      borne out in multiple patients enrolled as part of a recent clinical trial. These
      clinical adverse events seemingly overshadowed interesting behavioral
      stabilization and alterations of Abeta burden in these and other vaccinated
      patients, thus speaking to the potential of immunotherapy for AD. Understanding
      the mechanisms by which vaccines reduce Abeta burden in AD brain and the types of
      immune responses raised, as well as developing new modalities of vaccine delivery
      that facilitate the modulation of elicited immune responses, will undoubtedly
      lead to a new generation of efficacious Abeta immunotherapeutics with improved
      safety profiles.

PMID- 16293587
TI  - Neurofibromatosis pain is in the membrane. Focus on "sensory neurons from Nf1
      haploinsufficient mice exhibit increased excitability".

PMID- 16293588
TI  - GABA comes first to newly generated neurons. Focus on "GABAergic signal to
      newborn neurons in dentate gyrus".

PMID- 16293589
TI  - Transient voltage-dependent potassium currents are reduced in NTS neurons
      isolated from renal wrap hypertensive rats.
AB  - Whole cell patch-clamp measurements were made in neurons enzymatically dispersed
      from the nucleus of the solitary tract (NTS) to determine if alterations occur in
      voltage-dependent potassium channels from rats made hypertensive (HT) by
      unilateral nephrectomy/renal wrap for 4 wk. Some rats had the fluorescent tracer
      DiA applied to the aortic nerve before the experiment to identify NTS neurons
      receiving monosynaptic baroreceptor afferent inputs. Mean arterial pressure (MAP)
      was greater in 4-wk HT (165 +/- 5 mmHg, n = 26, P < 0.001) rats compared with
      normotensive (NT) rats (109 +/- 3 mmHg measured in 10 of 69 rats). Transient
      outward currents (TOCs) were observed in 67-82% of NTS neurons from NT and HT
      rats. At activation voltages from -10 to +10 mV, TOCs were significantly less in
      HT neurons compared with those observed in NT neurons (P < 0.001). There were no
      differences in the voltage-dependent activation kinetics, the voltage dependence
      of steady-state inactivation, and the rise and decay time constants of the TOCs
      comparing neurons isolated from NT and HT rats. The 4-aminopyridine-sensitive
      component of the TOC was significantly less in neurons from HT compared with NT
      rats (P < 0.001), whereas steady-state outward currents, whether or not sensitive
      to 4-aminopyridine or tetraethylammonium, were not different. Delayed excitation,
      studied under current clamp, was observed in 60-80% of NTS neurons from NT and HT
      rats and was not different comparing neurons from NT and HT rats. However,
      examination of the subset of NTS neurons exhibiting somatic DiA fluorescence
      revealed that DiA-labeled neurons from HT rats had a significantly shorter
      duration delayed excitation (n = 8 cells, P = 0.022) than DiA-labeled neurons
      from NT rats (n = 7 cells). Neurons with delayed excitation from HT rats had a
      significantly broader first action potential (AP) and a slower maximal downstroke
      velocity of repolarization compared with NT neurons with delayed excitation (P =
      0.016 and P = 0.014, respectively). The number of APs in the first 200 ms of a
      sustained depolarization was greater in HT than NT neurons (P = 0.012). These
      results suggest that HT of 4-wk duration reduces TOCs in NTS neurons, and this
      contributes to reduced delayed excitation and increased AP responses to
      depolarizing inputs. Such changes could alter baroreflex function in
      hypertension.

PMID- 16293590
TI  - Photic-induced sensitization: acquisition of an augmenting spike-wave response in
      the adult rat through repeated strobe exposure.
AB  - It is well established that patterns of sensory input can affect neuroplastic
      changes during early development. The scope and consequences of experience
      dependent plasticity in the adult are less well understood. We studied the
      possibility that repeated exposure to trains of stroboscopic stimuli could induce
      a sensitized and potentially aberrant response in ordinary individuals. Chronic
      electrocorticographic recording electrodes enabled measurement of responses in
      awake, freely moving animals. Normal adult rats, primarily Sprague-Dawley, were
      exposed to 20-40 strobe trains per day after a strobe-free adaptation period. The
      common response to strobe trains changed in 34/36 rats with development of a high
      amplitude spike-wave response that emerged fully by the third day of photic
      exposure. Onset of this sensitized response was marked by short-term augmentation
      of response to successive strobe flashes. The waveform generalized across the
      brain, reflected characteristics of the visual stimulus, as well as an inherent 6
      to 8-Hz pacing, and was suppressed with ethosuximide administration. Spike-wave
      episodes were self-limiting but could persist beyond the strobe period.
      Sensitization lasted 2-4 wk after last strobe exposure. The results indicate
      visual stimulation, by itself, can induce in adult rats an enduring sensitization
      of visual response with epileptiform characteristics. The results raise the
      question of the effects of such neuroplastic change on sensation and epileptiform
      events.

PMID- 16293591
TI  - Signal propagation in oblique dendrites of CA1 pyramidal cells.
AB  - The electrophysiological properties of the oblique branches of CA1 pyramidal
      neurons are largely unknown and very difficult to investigate experimentally.
      These relatively thin dendrites make up the majority of the apical tree surface
      area and constitute the main target of Schaffer collateral axons from CA3. Their
      electrogenic properties might have an important role in defining the
      computational functions of CA1 neurons. It is thus important to determine if and
      to what extent the back- and forward propagation of action potentials (AP) in
      these dendrites could be modulated by local properties such as morphology or
      active conductances. In the first detailed study of signal propagation in the
      full extent of CA1 oblique dendrites, we used 27 reconstructed three-dimensional
      morphologies and different distributions of the A-type K(+) conductance (K(A)),
      to investigate their electrophysiological properties by computational modeling.
      We found that the local K(A) distribution had a major role in modulating action
      potential back propagation, whereas the forward propagation of dendritic spikes
      originating in the obliques was mainly affected by local morphological
      properties. In both cases, signal processing in any given oblique was effectively
      independent of the rest of the neuron and, by and large, of the distance from the
      soma. Moreover, the density of K(A) in oblique dendrites affected spike
      conduction in the main shaft. Thus the anatomical variability of CA1 pyramidal
      cells and their local distribution of voltage-gated channels may suit a powerful
      functional compartmentalization of the apical tree.

PMID- 16293592
TI  - Involvement of dorsal column nucleus neurons in nociceptive transmission in aged
      rats.
AB  - To clarify the functional role of the dorsal column nucleus (DCN) in nociception
      in rats with advancing age, single neuronal activity and substance P-like
      immunoreactivity (SP-LI) of the gracile nucleus (GN) were studied in aged rats
      (29 to 34 mo old) and adult rats (9 to 12 mo old). A total of 122 neurons [aged:
      34 wide-dynamic-range (WDR), two nociceptive-specific (NS), and 32 low-threshold
      mechanical (LTM) neurons; adult: 22 WDR and 32 LTM neurons] were recorded from
      GN. For WDR neurons, the latency to antidromic activation of the ventral
      posterior lateral nucleus of the thalamus showed no difference between the aged
      and adult rats. Sciatic nerve stimulation with C-fiber intensity induced
      responses of GN with significantly longer latency in aged rats than in adults,
      whereas there was no difference in the response latency to A-fiber intensity
      stimulation. Background activity and afterdischarges were significantly higher in
      the aged rats than those in the adult rats. Responses to noxious mechanical and
      thermal stimuli were significantly greater in the aged rats during application of
      graded stimuli. There were no significant differences in responses to nonnoxious
      mechanical stimulus, mechanical response threshold, and the size of the receptive
      fields between neurons in the aged and adult rats. The area occupied by SP-LI
      fibers in the GN and the size of SP-LI dorsal root ganglia neurons were
      significantly larger in aged rats than in adults. The present findings suggest
      that the hyperexcitability of GN neurons could be involved in abnormal noxious
      pain sensations with advancing age.

PMID- 16293593
TI  - Calcium from internal stores triggers GABA release from retinal amacrine cells.
AB  - The Ca(2+) that promotes transmitter release is generally thought to enter
      presynaptic terminals through voltage-gated Ca(2+)channels. Using
      electrophysiology and Ca(2+) imaging, we show that, in amacrine cell dendrites,
      at least some of the Ca(2+) that triggers transmitter release comes from
      endoplasmic reticulum Ca(2+) stores. We show that both inositol 1,4,5
      trisphosphate receptors (IP(3)Rs) and ryanodine receptors (RyRs) are present in
      these dendrites and both participate in the elevation of cytoplasmic [Ca(2+)]
      during the brief depolarization of a dendrite. Only the Ca(2+) released through
      IP(3)Rs, however, seems to promote the release of transmitter. Antagonists for
      the IP(3)R reduced transmitter release, whereas RyR blockers had no effect.
      Application of an agonist for metabotropic glutamate receptor, known to liberate
      Ca(2+) from internal stores, enhanced both spontaneous and evoked transmitter
      release.

PMID- 16293594
TI  - Activity- and BDNF-induced plasticity of miniature synaptic currents in ES cell
      derived neurons integrated in a neocortical network.
AB  - In vitro differentiated embryonic stem (ES) cells have been proposed as potential
      donor cells for cell replacement therapies of neurodegenerative diseases. The
      functional synaptic integration of such cells appears conceivable because ES cell
      derived neurons are well known to establish excitatory and inhibitory synapses.
      However, long-term synaptic plasticity, a prerequisite of memory formation, has
      not yet been demonstrated at these synapses. After in vitro differentiation and
      purification by immunoisolation, we co-cultured ES cell-derived neurons with
      neocortical explants, which strongly innervated the ES cell-derived target
      neurons. ES cell-derived neurons exhibited action potential firing similar to
      primary cultured neocortical neurons. The formation of glutamatergic synapses was
      indicated by AMPA receptor-mediated miniature excitatory postsynaptic currents
      (AMPA mEPSCs). In addition, a N-methyl-D-aspartate receptor-mediated, D-2-amino-5
      phosphonopentanoic acid-sensitive mEPSC component was observed. We first studied
      activity-dependent homeostatic plasticity (synaptic scaling) of mEPSCs at
      glutamatergic synapses. Chronic blockade of action potential activity by TTX
      resulted in an increase in the amplitudes of AMPA mEPSCs. This indicates that ES
      cell-derived neurons are capable of a homeostatic regulation of postsynaptic AMPA
      receptors. In addition, we investigated neurotrophin-induced synaptic plasticity
      of mEPSCs at glutamatergic synapses. Chronic addition of brain-derived
      neurotrophic factor (BDNF; 100 ng/ml) to the culture medium resulted in an
      increase in both the frequency and the amplitudes of AMPA mEPSCs. These results
      suggest that BDNF induces the formation and/or the functional maturation of
      presynaptic release sites in parallel with an upregulation of postsynaptic AMPA
      receptors. Thus BDNF represents a potential co-factor that could improve
      functional synaptic integration of ES cell-derived neurons into neocortical
      networks.

PMID- 16293595
TI  - Siglec-H is an IPC-specific receptor that modulates type I IFN secretion through
      DAP12.
AB  - Natural interferon (IFN)-producing cells are the primary cell type responsible
      for production of type I IFN in response to viruses. Herein we report the
      identification of the first molecular marker of mouse natural interferon
      producing cells (IPCs), a novel member of the sialic acid-binding immunoglobulin
      (Ig)-like lectin (Siglec) family termed Siglec-H. Siglec-H is expressed
      exclusively on IPCs and is unique among Siglec proteins in that it associates
      with the adaptor protein DAP12. Moreover, we show that DAP12 modulates the type I
      IFN response of IPCs to a Toll-like receptor 9 (TLR9) agonist. This observation
      explains our previous finding that stimulation of IPCs with 440c, a Siglec-H
      specific antibody, reduces IPC secretion of type I IFN. Moreover, it supports a
      model in which engagement of DNAX-activation protein 12 (DAP12)-associated
      receptors with antibodies or low avidity endogenous ligands interferes with TLR
      mediated cellular activation.

PMID- 16293597
TI  - V617F mutation in JAK2 is associated with poorer survival in idiopathic
      myelofibrosis.
AB  - Most patients with polycythemia vera and half with idiopathic myelofibrosis and
      essential thrombocythemia have an acquired V617F mutation in JAK2. Using
      sensitive polymerase chain reaction (PCR)-based methods, we genotyped 152
      patients with idiopathic myelofibrosis to establish whether there were
      differences in presentation and outcome between those with and those without the
      mutation. Patients positive for V617F had higher neutrophil and white cell counts
      (P = .02) than did patients negative for V617F, but other diagnostic features
      were comparable between the 2 groups. Patients positive for V617F were less
      likely to require blood transfusion during follow-up (P = .03). Despite this,
      patients positive for V617F had poorer overall survival, even after correction
      for confounding factors (P = .01).

PMID- 16293596
TI  - A MAPK/HNRPK pathway controls BCR/ABL oncogenic potential by regulating MYC mRNA
      translation.
AB  - Altered mRNA translation is one of the effects exerted by the BCR/ABL oncoprotein
      in the blast crisis phase of chronic myelogenous leukemia (CML). Here, we report
      that in BCR/ABL+ cell lines and in patient-derived CML blast crisis mononuclear
      and CD34+ cells, p210(BCR/ABL) increases expression and activity of the
      transcriptional-inducer and translational-regulator heterogeneous nuclear
      ribonucleoprotein K (hnRNP K or HNRPK) in a dose- and kinase-dependent manner
      through the activation of the MAPK(ERK1/2) pathway. Furthermore, HNRPK down
      regulation and interference with HNRPK translation-but not transcription
      regulatory activity impairs cytokine-independent proliferation, clonogenic
      potential, and in vivo leukemogenic activity of BCR/ABL-expressing myeloid 32Dcl3
      and/or primary CD34+ CML-BC patient cells. Mechanistically, we demonstrate that
      decreased internal ribosome entry site (IRES)-dependent Myc mRNA translation
      accounts for the phenotypic changes induced by inhibition of the BCR/ABL-ERK
      dependent HNRPK translation-regulatory function. Accordingly, MYC protein but not
      mRNA levels are increased in the CD34+ fraction of patients with CML in
      accelerated and blastic phase but not in chronic phase CML patients and in the
      CD34+ fraction of marrow cells from healthy donors. Thus, BCR/ABL-dependent
      enhancement of HNRPK translation-regulation is important for BCR/ABL
      leukemogenesis and, perhaps, it might contribute to blast crisis transformation.

PMID- 16293598
TI  - CD38 orchestrates migration, survival, and Th1 immune response of human mature
      dendritic cells.
AB  - CD38, an ectoenzyme and a signaling receptor, is a novel marker of human mature
      monocyte-derived dendritic cells (MDDCs). The working hypothesis is that CD38 is
      not only a marker but also contributes to functions specifically gained by MDDCs
      with maturation. This was tested by assessing the role(s) of CD38 after signaling
      with agonistic anti-CD38 monoclonal antibodies or by blocking the interactions
      taking place between CD38 and CD31, its counterreceptor. The results indicate the
      following: (1) CD38 engagement in MDDCs ensures efficient chemotaxis and
      transendothelial migration driven by CC chemokine ligand 21 (CCL21); (2) CD38 is
      laterally associated with the CCL21-specific CC chemokine receptor 7 and with
      CD83 and CD11b; (3) CD38 localizes in membrane lipid domains; (4) CD38 signaling
      contributes to support longevity of lipopolysaccharide (LPS)-matured MDDCs after
      growth factor withdrawal; and (5) IFN-gamma is produced by cocultured T
      lymphocytes, thus affecting T-helper 1 (Th1) polarization. These data suggest
      that the localization of CD38 in lipid rafts and its multiple interactions with
      signaling receptors rule innate and adaptive immune responses by tuning DC
      migration, survival, and Th1-polarization ability. These findings may lay out the
      basis to assess the functional role(s) of human CD38 in infections, autoimmune
      diseases, and neoplastic disorders.

PMID- 16293599
TI  - Interferon-gamma-stimulated marrow stromal cells: a new type of nonhematopoietic
      antigen-presenting cell.
AB  - Several studies have demonstrated that marrow stromal cells (MSCs) can suppress
      allogeneic T-cell responses. However, the effect of MSCs on syngeneic immune
      responses has been largely overlooked. We describe here that primary MSCs derived
      from C57BL/6 mice behave as conditional antigen-presenting cells (APCs) and can
      induce antigen-specific protective immunity. Interferon gamma (IFNgamma)-treated
      C57BL/6 MSCs, but not unstimulated MSCs, cocultured with ovalbumin-specific major
      histocompatibility (MHC) class II-restricted hybridomas in the presence of
      soluble ovalbumin-induced significant production of interleukin-2 (IL-2) in an
      antigen dose-dependent manner (P < .005). IFNgamma-treated MSCs could further
      activate in vitro ovalbumin-specific primary transgenic CD4+ T cells. C57BL/6
      MSCs, however, were unable to induce antigen cross-presentation via the MHC class
      I pathway. When syngeneic mice were immunized intraperitoneally with ovalbumin
      pulsed IFNgamma-treated MSCs, they developed antigen-specific cytotoxic CD8+ T
      cells and became fully protected (10 of 10 mice) against ovalbumin-expressing
      E.G7 tumors. Human MSCs were also studied for antigen-presenting functions.
      IFNgamma-treated DR1-positive human MSCs, but not unstimulated human MSCs,
      induced significant production of IL-2 when cocultured with DR1-restricted
      influenza-specific humanized T-cell hybridomas in the presence of purified
      influenza matrix protein 1. Taken together, our data strongly suggest that MSCs
      behave as conditional APCs in syngeneic immune responses.

PMID- 16293601
TI  - Suicide gene therapy of graft-versus-host disease induced by central memory human
      T lymphocytes.
AB  - In allogeneic hematopoietic cell transplantation (allo-HCT), the immune
      recognition of host antigens by donor T lymphocytes leads to a beneficial graft
      versus-leukemia (GvL) effect as well as to life-threatening graft-versus-host
      disease (GvHD). Genetic modification of T lymphocytes with a retroviral vector
      (RV) expressing the herpes simplex virus-thymidine kinase (TK) suicide gene
      confers selective sensitivity to the prodrug ganciclovir (GCV). In patients, the
      infusion of TK+ lymphocytes and the subsequent administration of GCV resulted in
      a time-wise modulation of antihost reactivity for a GvL effect, while controlling
      GvHD. Because activation required for genetic modification with RV may reduce
      antihost reactivity, we investigated the requirements for maximizing the potency
      of human TK+ lymphocytes. Whereas T-cell receptor triggering alone led to
      effector memory (EM) TK+ lymphocytes, the addition of CD28 costimulation through
      cell-sized beads resulted in the generation of central memory (CM) TK+
      lymphocytes. In a quantitative model for GvHD using nonobese diabetic/severely
      combined immunodeficient mice, CM TK+ lymphocytes were more potent than EM TK+
      lymphocytes. GCV administration efficiently controlled GvHD induced by CM TK+
      lymphocytes. These results warrant the clinical investigation of CM suicide gene
      modified human T lymphocytes for safe and effective allo-HCT.

PMID- 16293600
TI  - The structure of the GPIb-filamin A complex.
AB  - Filamin A (FLNa), a dimeric actin cross-linking and scaffold protein with
      numerous intracellular binding partners, anchors the platelet adhesion
      glycoprotein (GP) Ib-IX-V receptor to actin cytoskeleton. We mapped the GPIbalpha
      binding site to a single domain of FLNa and resolved the structure of this domain
      and its interaction complex with the corresponding GPIbalpha cytoplasmic domain.
      This is the first atomic structure of this class of membrane glycoprotein
      cytoskeleton connection. GPIbalpha binds in a groove formed between the C and D
      beta strands of FLNa domain 17. The interaction is strikingly similar to that
      between the beta7 integrin tail and a different FLNa domain, potentially defining
      a conserved motif for FLNa binding. Nevertheless, the structures also reveal
      specificity of the interfaces, which explains different regulatory mechanisms. To
      verify the topology of GPIb-FLNa interaction we also purified the native complex
      from platelets and showed that GPIb interacts with the C-terminus of FLNa, which
      is in accordance with our biochemical and structural data.

PMID- 16293602
TI  - The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion.
AB  - The molecular mechanism responsible for a decline of stem cell functioning after
      replicative stress remains unknown. We used mouse embryonic fibroblasts (MEFs)
      and hematopoietic stem cells (HSCs) to identify genes involved in the process of
      cellular aging. In proliferating and senescent MEFs one of the most
      differentially expressed transcripts was Enhancer of zeste homolog 2 (Ezh2), a
      Polycomb group protein (PcG) involved in histone methylation and deacetylation.
      Retroviral overexpression of Ezh2 in MEFs resulted in bypassing of the senescence
      program. More importantly, whereas normal HSCs were rapidly exhausted after
      serial transplantations, overexpression of Ezh2 completely conserved long-term
      repopulating potential. Animals that were reconstituted with 3 times serially
      transplanted control bone marrow cells all died due to hematopoietic failure. In
      contrast, similarly transplanted Ezh2-overexpressing stem cells restored stem
      cell quality to normal levels. In a "genetic genomics" screen, we identified
      novel putative Ezh2 target or partner stem cell genes that are associated with
      chromatin modification. Our data suggest that stabilization of the chromatin
      structure preserves HSC potential after replicative stress.

PMID- 16293604
TI  - Patterns of expression, membrane localization, and effects of ectopic expression
      suggest a function for MS4a4B, a CD20 homolog in Th1 T cells.
AB  - The membrane-spanning 4A (MS4A) family of proteins includes CD20, Fc
      epsilonRIbeta, and HTm4, whose genes are grouped in a chromosomal location that
      is associated with increased susceptibility to allergy and atopic asthma. One
      family member, Chandra/MS4a4B, was reported to be expressed in T helper 1 (Th1) T
      cells but not Th2 T cells. In the present study, Ms4a4b was isolated in a screen
      of genes differentially expressed during thymocyte development. MS4a4B was
      detected in immature CD4- CD8- CD44+ CD25- thymocytes, turned off during further
      stages of thymocyte development and reexpressed in mature single-positive
      thymocytes. MS4a4B expression was found in naive CD8+ and CD4+ peripheral T cells
      and natural killer (NK) cells but not in B cells. MS4a4B is expressed at the cell
      surface with its C-terminus located in the cytoplasm. When expressed in a T-cell
      hybridoma by retroviral vector, MS4a4B protein constitutively associated with
      lipid raft microdomains, whereas in primary T cells endogenous MS4a4B protein
      became enriched in rafts after T-cell activation. Overexpression of MS4a4B in
      primary CD4+ T-cell blasts enhanced T-cell receptor (TCR)-induced Th1 cytokine
      production. These results suggest that MS4a4B expression is tightly regulated
      during T-cell development and that MS4a4B expression promotes Th1 function and/or
      differentiation.

PMID- 16293603
TI  - Pharmacodynamics of cytarabine alone and in combination with 7
      hydroxystaurosporine (UCN-01) in AML blasts in vitro and during a clinical trial.
AB  - Chk1 and Akt signaling facilitate survival of cells treated with nucleoside
      analogues. Activation of Chk1 in response to cytarabine (ara-C) induced an S
      phase checkpoint characterized by the inhibition of Cdk2, cell cycle arrest, no
      change in constitutively active Akt, or low-stress kinase signaling in ML-1
      cells. However, inhibition of Chk1 by UCN-01 in S-phase-arrested cells resulted
      in an abrogation of the checkpoint, inhibition of Akt, activation of JNK, and a
      rapid induction of apoptosis. Similarly, primary acute myelogenous leukemia (AML)
      blasts exposed to ara-C and UCN-01 demonstrated a selective loss in cloning
      potential when compared with normal progenitors. Therefore, we evaluated a pilot
      clinical trial of ara-C in combination with UCN-01 in patients with relapsed AML.
      Blasts from some patients demonstrated a previously activated Chk1-Cdk2 DNA
      damage response pathway that decreased during therapy. Constitutively
      phosphorylated Akt kinase declined on addition of UCN-01 to the ara-C infusion,
      an action accompanied by an activation of JNK and reduction in absolute AML blast
      counts. Thus, use of UCN-01 in combination with ara-C decreases Chk1
      phosphorylation, inhibits the Akt survival pathway, and activates JNK during the
      course of therapy, offering a rationale for the cytotoxic action of this
      combination during AML treatment.

PMID- 16293606
TI  - Size regulation of von Willebrand factor-mediated platelet thrombi by ADAMTS13 in
      flowing blood.
AB  - The metalloproteinase ADAMTS13 regulates the size of released von Willebrand
      factor (VWF) multimers bound to endothelial cells, but it is unknown whether it
      can cleave plasma VWF during thrombogenesis. To address this issue, we perfused
      blood over immobilized VWF and used videomicroscopy to visualize an activation
      independent platelet aggregation process mediated by soluble VWF at shear rates
      greater than 10 000 s(-1). At normal Ca2+ concentration, platelets formed rolling
      as well as surface-attached clusters that grew larger during the first 5 minutes
      but then lost more than 70% of their mass by 10 minutes. In contrast, platelet
      clusters were stable in size when metal ions were chelated, anti-ADAMTS13 IgG
      were added, or washed blood cells were perfused with purified VWF but no plasma.
      In the latter case, addition of recombinant ADAMTS13 reduced platelet cluster
      size by more than 70%. Incubating ADAMTS13 with VWF before perfusion did not
      prevent the initial platelet clustering, indicating that the enzyme may act on
      platelet-bound VWF under shear stress. At the concentrations tested, ADAMTS13 had
      no effect on platelet aggregates formed upon blood perfusion over collagen
      fibrils. ADAMTS13, therefore, may regulate thrombus size preferentially when the
      cohesion between platelets depends on VWF binding induced by pathologically
      elevated shear stress.

PMID- 16293605
TI  - Neutrophils, lymphocytes, and monocytes exhibit diverse behaviors in
      transendothelial and subendothelial migrations under coculture with smooth muscle
      cells in disturbed flow.
AB  - Atherosclerosis develops at regions of the arterial tree exposed to disturbed
      flow. The early stage of atherogenesis involves the adhesion of leukocytes (white
      blood cells [WBCs]) to and their transmigration across endothelial cells (ECs),
      which are located in close proximity to smooth muscle cells (SMCs). We
      investigated the effects of EC/SMC coculture and disturbed flow on the adhesion
      and transmigration of 3 types of WBCs (neutrophils, peripheral blood lymphocytes
      [PBLs], and monocytes) using our vertical-step flow (VSF) chamber, in which ECs
      were cocultured with SMCs in collagen gels. Such coculture significantly
      increased the adhesion and transmigration of neutrophils, PBLs, and monocytes
      under VSF, particularly in the reattachment area, where the rolling velocity of
      WBCs and their transmigration time were decreased, as compared with the other
      areas. Neutrophils, PBLs, and monocytes showed different subendothelial migration
      patterns under VSF. Their movements were more random and shorter in distance in
      the reattachment area. Coculture of ECs and SMCs induced their expressions of
      adhesion molecules and chemokines, which contributed to the increased WBC
      adhesion and transmigration. Our findings provide insights into the mechanisms of
      WBC interaction with the vessel wall (composed of ECs and SMCs) under the complex
      flow environments found in regions of prevalence for atherogenesis.

PMID- 16293607
TI  - High frequency of alternative first exons in erythroid genes suggests a critical
      role in regulating gene function.
AB  - The human genome uses alternative pre-mRNA splicing as an important mechanism to
      encode a complex proteome from a relatively small number of genes. An unknown
      number of these genes also possess multiple transcriptional promoters and
      alternative first exons that contribute another layer of complexity to gene
      expression mechanisms. Using a collection of more than 100 erythroid-expressed
      genes as a test group, we used genome browser tools and genetic databases to
      assess the frequency of alternative first exons in the genome. Remarkably, 35% of
      these erythroid genes show evidence of alternative first exons. The majority of
      the candidate first exons are situated upstream of the coding exons, whereas a
      few are located internally within the gene. Computational analyses predict
      transcriptional promoters closely associated with many of the candidate first
      exons, supporting their authenticity. Importantly, the frequent presence of
      consensus translation initiation sites among the alternative first exons suggests
      that many proteins have alternative N-terminal structures whose expression can be
      coupled to promoter choice. These findings indicate that alternative promoters
      and first exons are more widespread in the human genome than previously
      appreciated and that they may play a major role in regulating expression of
      selected protein isoforms in a tissue-specific manner.

PMID- 16293609
TI  - GILZ expression in human dendritic cells redirects their maturation and prevents
      antigen-specific T lymphocyte response.
AB  - Interleukin (IL)-10 and glucocorticoids (GCs) inhibit the ability of antigen
      presenting dendritic cells (DCs) to stimulate T lymphocytes. We show that
      induction of GILZ (GC-induced leucine zipper) is involved in this phenomenon. IL
      10, dexamethasone (DEX), and transforming growth factor (TGF)beta stimulate GILZ
      production in human immature DCs derived from monocytes and from CD34+ cells.
      GILZ is necessary and sufficient for DEX, IL-10, and TGFbeta modulation of CD80,
      CD83, CD86, immunoglobulin-like transcript (ILT)-3, and B7-H1 expression by DCs,
      and alteration of DC functions. GILZ stimulates the production of IL-10 by
      immature DCs and prevents the production of inflammatory chemokines by CD40L
      activated DCs. In contrast, GILZ does not prevent CD40 ligand-mediated inhibition
      of phagocytosis, indicating that it affects some but not all aspects of DC
      maturation. GILZ prevents DCs from activating antigen-specific T lymphocyte
      responses. Administration of GCs to patients stimulates GILZ expression in their
      circulating antigen-presenting cells, and this contributes to the weak lymphocyte
      responses of GC-treated patients. Thus, regulation of GILZ expression is an
      important factor determining the decision of DCs whether or not to stimulate T
      lymphocytes, and IL-10, GCs, and TGFbeta share this mechanism for influencing DC
      functions and the balance between immune response and tolerance.

PMID- 16293608
TI  - Identification of glucocorticoid-response genes in children with acute
      lymphoblastic leukemia.
AB  - The ability of glucocorticoids (GCs) to kill lymphoid cells led to their
      inclusion in essentially all chemotherapy protocols for lymphoid malignancies,
      particularly childhood acute lymphoblastic leukemia (ALL). GCs mediate apoptosis
      via their cognate receptor and subsequent alterations in gene expression.
      Previous investigations, including expression profiling studies with subgenome
      microarrays in model systems, have led to a number of attractive, but
      conflicting, hypotheses that have never been tested in a clinical setting. Here,
      we present a comparative whole-genome expression profiling approach using
      lymphoblasts (purified at 3 time points) from 13 GC-sensitive children undergoing
      therapy for ALL. For comparisons, expression profiles were generated from an
      adult patient with ALL, peripheral blood lymphocytes from GC-exposed healthy
      donors, GC-sensitive and -resistant ALL cell lines, and mouse thymocytes treated
      with GCs in vivo and in vitro. This generated an essentially complete list of GC
      regulated candidate genes in clinical settings and experimental systems, allowing
      immediate analysis of any gene for its potential significance to GC-induced
      apoptosis. Our analysis argued against most of the model-based hypotheses and
      instead identified a small number of novel candidate genes, including PFKFB2, a
      key regulator of glucose metabolism; ZBTB16, a putative transcription factor; and
      SNF1LK, a protein kinase implicated in cell-cycle regulation.

PMID- 16293610
TI  - Specialization, kinetics, and repertoire of type 1 interferon responses by human
      plasmacytoid predendritic cells.
AB  - Recent studies suggest plasmacytoid predendritic cells (pDCs) and myeloid
      dendritic cells (mDCs) have the functional plasticity to produce similar amounts
      of type 1 interferons (IFNs) and interleukin-12 (IL-12), challenging the concept
      and existence of DC subsets with distinct function. In this study, we demonstrate
      that previous studies showed human pDCs produce large amounts of IL-12 because of
      contaminating mDCs. Using highly purified human DC subsets, we found that
      although pDCs make 300 times more IFN-alpha than mDCs and mDCs make 13 times more
      IL-12 p70 than pDCs in response to all the toll-like receptor ligands and CD40
      ligands, pDCs rapidly make large amounts of IFN-alpha within the first 12 hours
      of activation and become refractory to further stimulation. pDCs preferentially
      expressed the transcriptional factors critical for type 1 IFN, but not for IL-12
      transcription, and they dedicated 60% of new transcriptional activity to make 19
      type 1 IFN subtypes. This study provides formal proof that the plasticity of DC
      subsets is limited and that different DC subsets evolve to perform distinct
      functions in linking innate and adaptive immunity.

PMID- 16293611
TI  - Allogeneic and syngeneic hematopoietic cell transplantation in patients with
      amyloid light-chain amyloidosis: a report from the European Group for Blood and
      Marrow Transplantation.
AB  - Using the European Group for Blood and Marrow Transplantation (EBMT) registry, we
      retrospectively studied 19 patients with AL (amyloid light-chain) amyloidosis who
      underwent allogeneic (allo; n = 15) or syngeneic (syn; n = 4) hematopoietic stem
      cell transplantation (SCT) between 1991 and 2003. For allo-SCT, full-intensity
      conditioning was used in 7 patients and reduced-intensity conditioning (RIC) in 8
      patients. Engraftment was durable in 12 of those 15 patients. The median follow
      up time is 19 months. Kaplan-Meier probabilities of overall and progression-free
      survival were 60% and 53% at 1 year, respectively. Overall, 40% of patients died
      of transplant-related mortality (TRM). Best hematologic response after SCT was
      complete remission (CR) and partial remission (PR) in 8 and 2 patients,
      respectively, leading to an organ response in 8 of these patients. Seven of the
      10 patients in remission are long-term survivors. In 5 of 7 evaluable patients in
      CR, chronic graft-versus-host disease (GvHD) was observed, indicating the
      contribution of immune effects to disease control. The main clinical problem was
      cardiac failure in patients with poor performance status due to amyloidosis or in
      combination with severe infections. These data suggest that allo-SCT might be a
      promising and potentially curative treatment modality for selected patients with
      AL amyloidosis.

PMID- 16293612
TI  - Increased membrane affinity of the C1 domain of protein kinase Cdelta compensates
      for the lack of involvement of its C2 domain in membrane recruitment.
AB  - Protein kinase C (PKC) family members are allosterically activated following
      membrane recruitment by specific membrane-targeting modules. Conventional PKC
      isozymes are recruited to membranes by two such modules: a C1 domain, which binds
      diacylglycerol (DAG), and a C2 domain, which is a Ca2+-triggered phospholipid
      binding module. In contrast, novel PKC isozymes respond only to DAG, despite the
      presence of a C2 domain. Here, we address the molecular mechanism of membrane
      recruitment of the novel isozyme PKCdelta. We show that PKCdelta and a
      conventional isozyme, PKCbetaII, bind membranes with comparable affinities.
      However, dissection of the contribution of individual domains to this binding
      revealed that, although the C2 domain is a major determinant in driving the
      interaction of PKCbetaII with membranes, the C2 domain of PKCdelta does not bind
      membranes. Instead, the C1B domain is the determinant that drives the interaction
      of PKCdelta with membranes. The C2 domain also does not play any detectable role
      in the activity or subcellular location of PKCdelta in cells; in vivo imaging
      studies revealed that deletion of the C2 domain does not affect the stimulus
      dependent translocation or activity of PKCdelta. Thus, the increased affinity of
      the C1 domain of PKCdelta allows this isozyme to respond to DAG alone, whereas
      conventional PKC isozymes require the coordinated action of Ca2+ binding to the
      C2 domain and DAG binding to the C1 domain for activation.

PMID- 16293613
TI  - The second intracellular loop of the calcitonin gene-related peptide receptor
      provides molecular determinants for signal transduction and cell surface
      expression.
AB  - The calcitonin gene-related peptide (CGRP) receptor is a heterodimer of a family
      B G-protein-coupled receptor, calcitonin receptor-like receptor (CLR), and the
      accessory protein receptor activity modifying protein 1. It couples to G(s), but
      it is not known which intracellular loops mediate this. We have identified the
      boundaries of this loop based on the relative position and length of the
      juxtamembrane transmembrane regions 3 and 4. The loop has been analyzed by
      systematic mutagenesis of all residues to alanine, measuring cAMP accumulation,
      CGRP affinity, and receptor expression. Unlike rhodopsin, ICL2 of the CGRP
      receptor plays a part in the conformational switch after agonist interaction. His
      216 and Lys-227 were essential for a functional CGRP-induced cAMP response. The
      effect of (H216A)CLR is due to a disruption to the cell surface transport or
      surface stability of the mutant receptor. In contrast, (K227A)CLR had wild-type
      expression and agonist affinity, suggesting a direct disruption to the downstream
      signal transduction mechanism of the CGRP receptor. Modeling suggests that the
      loop undergoes a significant shift in position during receptor activation,
      exposing a potential G-protein binding pocket. Lys-227 changes position to point
      into the pocket, potentially allowing it to interact with bound G-proteins. His
      216 occupies a position similar to that of Tyr-136 in bovine rhodopsin, part of
      the DRY motif of the latter receptor. This is the first comprehensive analysis of
      an entire intracellular loop within the calcitonin family of G-protein-coupled
      receptor. These data help to define the structural and functional characteristics
      of the CGRP-receptor and of family B G-protein-coupled receptors in general.

PMID- 16293614
TI  - Protein-tyrosine kinase and GTPase signals cooperate to phosphorylate and
      activate Wiskott-Aldrich syndrome protein (WASP)/neuronal WASP.
AB  - Protein-tyrosine kinases and Rho GTPases regulate many cellular processes,
      including the reorganization and dynamics of the actin cytoskeleton. The Wiskott
      Aldrich syndrome protein (WASP) and its homolog neuronal WASP (N-WASP) are
      effectors of the Rho GTPase Cdc42 and provide a direct link between activated
      membrane receptors and the actin cytoskeleton. WASP and N-WASP are also regulated
      by a large number of other activators, including protein-tyrosine kinases,
      phosphoinositides, and Src homology 3-containing adaptor proteins, and can
      therefore serve as signal integrators inside cells. Here we show that Cdc42 and
      the Src family kinase Lck cooperate at two levels to enhance WASP activation.
      First, autoinhibition in N-WASP decreases the efficiency (kcat/Km) of
      phosphorylation and dephosphorylation of the GTPase binding domain by 30- and 40
      fold, respectively, and this effect is largely reversed by Cdc42. Second, Cdc42
      and the Src homology 3-Src homology 2 module of Lck cooperatively stimulate the
      activity of phosphorylated WASP, with coupling energy of approximately 2.4
      kcal/mol between the two activators. These combined effects provide mechanisms
      for high specificity in WASP activation by coincident GTPase and kinase signals.

PMID- 16293615
TI  - G protein-induced trafficking of voltage-dependent calcium channels.
AB  - Calcium channels are well known targets for inhibition by G protein-coupled
      receptors, and multiple forms of inhibition have been described. Here we report a
      novel mechanism for G protein-mediated modulation of neuronal voltage-dependent
      calcium channels that involves the destabilization and subsequent removal of
      calcium channels from the plasma membrane. Imaging experiments in living sensory
      neurons show that, within seconds of receptor activation, calcium channels are
      cleared from the membrane and sequestered in clathrin-coated vesicles. Disruption
      of the L1-CAM-ankyrin B complex with the calcium channel mimics transmitter
      induced trafficking of the channels, reduces calcium influx, and decreases
      exocytosis. Our results suggest that G protein-induced removal of plasma membrane
      calcium channels is a consequence of disrupting channel-cytoskeleton interactions
      and might represent a novel mechanism of presynaptic inhibition.

PMID- 16293616
TI  - Prostaglandin E2 regulates the nuclear receptor NR4A2 in colorectal cancer.
AB  - Many lines of research implicate cyclooxygenase 2-derived prostaglandins in tumor
      growth and metastasis. More specifically, we have shown that prostaglandin E2
      (PGE2) promotes cell proliferation and invasion through transactivation of the
      epidermal growth factor receptor, initiates immune evasion through induction of
      decay accelerating factor, and transactivates peroxisome proliferator-activated
      receptor delta, leading to increased polyp size and multiplicity. We continue to
      identify novel PGE2 target genes in colorectal carcinoma cells and report here
      that an immediate early gene, nuclear factor NR4A2 (Nurr1), is induced by PGE2
      that in turn regulates cell death. Originally described as a critical
      dopaminergic neuron growth factor receptor, NR4A2 expression is rapidly but
      transiently induced by PGE2 in a cAMP/protein kinase A-dependent manner. NR4A2
      binds to the cognate NBRE response element and enhances transcription of a
      reporter construct in colorectal carcinoma cells. Furthermore, NR4A2 expression
      is elevated in Apc-/+ mouse adenomas and its levels were further increased
      following PGE2 treatment. Human colorectal cancers relative to matched normal
      mucosa showed increased NR4A2 expression. Although not previously described in
      epithelial tissues, NR4A2 protein localizes to proliferating crypts of Apc-/+
      mouse intestine. Finally, functional studies reveal that PGE2-mediated protection
      from apoptosis is completely inhibited by a dominant-negative NR4A2 construct.
      Building on previous reports from our group on the peroxisome proliferator
      activated receptor family of nuclear receptors, these most recent data suggest
      that NR4A2, a member of another family of nuclear receptors can stimulate
      progression of colorectal cancer downstream from cyclooxygenase 2-derived PGE2.

PMID- 16293617
TI  - erbB1 functions as a sensor of airway epithelial integrity by regulation of
      protein phosphatase 2A activity.
AB  - Two enzymes, protein phosphatase 2A and atypical protein kinase C, are associated
      with the tight junction and regulate its function. For example, phosphorylation
      of the tight junction protein occludin is required for its incorporation into the
      junction. The association of a kinase and phosphatase with the tight junction
      suggests that a balance between their activities exists and is required for
      normal tight junction function. This hypothesis predicts that loss of epithelial
      integrity may disrupt this balance in such a way as to facilitate restoration of
      epithelial integrity. Our previous data have shown that apically localized growth
      factors segregate from their basolaterally localized erbB receptors. Loss of
      epithelial integrity allows ligand access to the basolateral membrane where it
      immediately binds to and activates erbB receptors. We found that activation of
      erbB1 leads to phosphorylation of protein phosphatase 2A, inhibiting its
      activity. Importantly, this phosphorylation event was dependent on factors in the
      overlying airway surface liquid; washing away this liquid prevented
      phosphorylation. erbB1-mediated inhibition of phosphatase activity would shift
      the balance in favor of the kinase such that tight junction proteins would regain
      their phosphorylation, allowing for their incorporation into the junction
      complex. This mechanism provides a rapid means of sensing the loss of epithelial
      integrity and subsequently restoring barrier function.

PMID- 16293618
TI  - Shank2 associates with and regulates Na+/H+ exchanger 3.
AB  - Na+/H+ exchanger 3 (NHE3) plays a pivotal role in transepithelial Na+ and HCO3(-)
      absorption across a wide range of epithelia in the digestive and renal
      genitourinary systems. Accumulating evidence suggests that PDZ-based adaptor
      proteins play an important role in regulating the trafficking and activity of
      NHE3. A search for NHE3-binding modular proteins using yeast two-hybrid assays
      led us to the PDZ-based adaptor Shank2. The interaction between Shank2 and NHE3
      was further confirmed by immunoprecipitation and surface plasmon resonance
      studies. When expressed in PS120/NHE3 cells, Shank2 increased the membrane
      expression and basal activity of NHE3 and attenuated the cAMP-dependent
      inhibition of NHE3 activity. Furthermore, knock-down of native Shank2 expression
      in Caco-2 epithelial cells by RNA interference decreased NHE3 protein expression
      as well as activity but amplified the inhibitory effect of cAMP on NHE3. These
      results indicate that Shank2 is a novel NHE3 interacting protein that is involved
      in the fine regulation of transepithelial salt and water transport through
      affecting NHE3 expression and activity.

PMID- 16293619
TI  - Thermodynamics of beta-catenin-ligand interactions: the roles of the N- and C
      terminal tails in modulating binding affinity.
AB  - beta-Catenin is a structural component of adherens junctions, where it binds to
      the cytoplasmic domain of cadherin cell adhesion molecules. beta-Catenin is also
      a transcriptional coactivator in the Wnt signaling pathway, where it binds to
      Tcf/Lef family transcription factors. In the absence of a Wnt signal,
      nonjunctional beta-catenin is present in a multiprotein complex containing the
      proteins axin and adenomatous polyposis coli (APC), both of which bind directly
      to beta-catenin. The thermodynamics of beta-catenin binding to E-cadherin, Lef-1,
      APC, axin, and the transcriptional inhibitor ICAT have been determined by
      isothermal titration calorimetry. Most of the interactions showed large,
      unfavorable entropy changes, consistent with these ligands being natively
      unstructured in the absence of beta-catenin. Phosphorylation of serine residues
      present in a sequence motif common to cadherins and APC increased the affinity
      for beta-catenin 300-700-fold, and surface plasmon resonance measurements
      revealed that phosphorylation of E-cadherin both enhanced its on rate and
      decreased its off rate. The effects of the N- and C-terminal "tails" that flank
      the beta-catenin armadillo repeat domain on ligand binding have also been
      investigated using constructs lacking one or both tails. Contrary to earlier
      studies that employed less direct binding assays, the tails did not affect the
      affinity of beta-catenin for tight ligands such as E-cadherin, Lef-1, and
      phosphorylated APC. However, the beta-catenin C-terminal tail was found to
      decrease the affinity for the weaker ligands APC and axin, suggesting that this
      region may have a regulatory role in beta-catenin degradation.

PMID- 16293620
TI  - Structural determinants for the binding of anthrax lethal factor to oligomeric
      protective antigen.
AB  - Anthrax lethal toxin assembles at the surface of mammalian cells when the lethal
      factor (LF) binds via its amino-terminal domain, LF(N), to oligomeric forms of
      activated protective antigen (PA). LF x PA complexes are then trafficked to
      acidified endosomes, where PA forms heptameric pores in the bounding membrane and
      LF translocates through these pores to the cytosol. We used enhanced peptide
      amide hydrogen/deuterium exchange mass spectrometry and directed mutagenesis to
      define the surface on LF(N) that interacts with PA. A continuous surface
      encompassing one face of LF(N) became protected from deuterium exchange when
      LF(N) was bound to a PA dimer. Directed mutational analysis demonstrated that
      residues within this surface on LF(N) interact with Lys-197 on two PA subunits
      simultaneously, thereby showing that LF(N) spans the PA subunit:subunit interface
      and explaining why heptameric PA binds a maximum of three LF(N) molecules. Our
      results elucidate the structural basis for anthrax lethal toxin assembly and may
      be useful in developing drugs to block toxin action.

PMID- 16293621
TI  - Analyses of variant acid beta-glucosidases: effects of Gaucher disease mutations.
AB  - Acid beta-glucosidase (GCase) is a 497-amino acid, membrane-associated lysosomal
      exo-beta-glucosidase whose defective activity leads to the Gaucher disease
      phenotypes. To move toward a structure/function map for disease mutations, 52
      selected single amino acid substitutions were introduced into GCase, expressed in
      an insect cell system, purified, and characterized for basic kinetic, stability,
      and activator response properties. The variant GCases from Gaucher disease
      patients and selected variant GCases from the mouse had decreased relative k(cat)
      and differential effects on active site binding and/or attachment of mechanism
      based covalent (conduritol B epoxide) or reversible (deoxynojirimycin
      derivatives) inhibitors. A defect in negatively charged phospholipid activation
      was present in the majority of variant GCases but was increased in two, N370S and
      V394L. Deficits in saposin C enhancement of k(cat) were present in variant GCases
      involving residues 48-122, whereas approximately 2-fold increases were obtained
      with the L264I GCase. About 50% of variant GCases each had wild-type or increased
      sensitivity to in vitro cathepsin D digestion. Mapping of these properties onto
      the crystal structures of GCase indicated wide dispersion of functional
      properties that can affect catalytic function and stability. Site-directed
      mutagenesis of cysteine residues showed that the disulfide bonds, Cys(4)-Cys(16)
      and Cys(18)-Cys(23), and a free Cys(342) were essential for activity; the free
      Cys(126) and Cys(248) were not. Relative k(cat) was highly sensitive to a His
      substitution at Arg(496) but not at Arg(495). These studies and high phylogenetic
      conservation indicate localized and general structural effects of Gaucher disease
      mutations that were not obvious from the nature of the amino acid substitution,
      including those predicted to be nondisruptive (e.g. Val --> Leu). These results
      provide initial studies for the engineering of variant GCases and, potentially,
      molecular chaperones for therapeutic use.

PMID- 16293622
TI  - Localization of TLR2 and MyD88 to Chlamydia trachomatis inclusions. Evidence for
      signaling by intracellular TLR2 during infection with an obligate intracellular
      pathogen.
AB  - Chlamydia trachomatis is an obligate intracellular gram-negative pathogen and the
      etiologic agent of significant ocular and genital tract diseases. Chlamydiae
      primarily infect epithelial cells, and the inflammatory response of these cells
      to the infection directs both the innate and adaptive immune response. This study
      focused on determining the cellular immune receptors involved in the early events
      following infection with the L2 serovar of C. trachomatis. We found that dominant
      negative MyD88 inhibited interleukin-8 (IL-8) secretion during a productive
      infection with chlamydia. Furthermore, expression of Toll-like receptor (TLR)-2
      was required for IL-8 secretion from infected cells, whereas the effect of
      TLR4/MD-2 expression was minimal. Cell activation was dependent on infection with
      live, replicating bacteria, because infection with UV-irradiated bacteria and
      treatment of infected cells with chloramphenicol, but not ampicillin, abrogated
      the induction of IL-8 secretion. Finally, we show that both TLR2 and MyD88 co
      localize with the intracellular chlamydial inclusion, suggesting that TLR2 is
      actively engaged in signaling from this intracellular location. These data
      support the role of TLR2 in the host response to infection with C. trachomatis.
      Our data further demonstrate that TLR2 and the adaptor MyD88 are specifically
      recruited to the bacterial or inclusion membrane during a productive infection
      with chlamydia and provide the first evidence that intracellular TLR2 is
      responsible for signal transduction during infection with an intracellular
      bacterium.

PMID- 16293623
TI  - DNA replication stress-induced phosphorylation of cyclic AMP response element
      binding protein mediated by ATM.
AB  - The DNA damage-response regulators ATM (ataxia-telangiectasia-mutated) and ATR
      (ATM-Rad3-related) are structurally and functionally related protein kinases that
      exhibit nearly identical substrate specificities in vitro. Current paradigms hold
      that the relative contributions of ATM and ATR to nuclear substrate
      phosphorylation are dictated by the type of initiating DNA lesion; ATM-dependent
      substrate phosphorylation is principally activated by DNA double strand breaks,
      whereas ATR-dependent substrate phosphorylation is induced by UV light and other
      forms of DNA replication stress. In this report, we employed the cyclic AMP
      response element-binding (CREB) protein to provide evidence for substrate
      discrimination by ATM and ATR in cellulo. ATM and ATR phosphorylate CREB in
      vitro, and CREB is phosphorylated on Ser-121 in intact cells in response to
      ionizing radiation (IR), UV light, and hydroxyurea. The UV light- and hydroxyurea
      induced phosphorylation of CREB was delayed in comparison to the canonical ATR
      substrate CHK1, suggesting potentially different mechanisms of phosphorylation.
      UV light-induced CREB phosphorylation temporally correlated with ATM
      autophosphorylation on Ser-1981, and an ATM-specific small interfering RNA
      suppressed CREB phosphorylation in response to this stimulus. UV light-induced
      CREB phosphorylation was absent in ATM-deficient cells, confirming that ATM is
      required for CREB phosphorylation in UV irradiation-damaged cells. Interestingly,
      RNA interference-mediated suppression of ATR partially inhibited CREB
      phosphorylation in response to UV light, which correlated with reduced
      phosphorylation of ATM on Ser-1981. These findings suggest that ATM is the major
      genotoxin-induced CREB kinase in mammalian cells and that ATR lies upstream of
      ATM in a UV light-induced signaling pathway.

PMID- 16293624
TI  - Immunogenicity and protective efficacy of Bacillus anthracis poly-gamma-D
      glutamic acid capsule covalently coupled to a protein carrier using a novel
      triazine-based conjugation strategy.
AB  - The capsular polypeptide of Bacillus anthracis is composed of a unique
      polyglutamic acid polymer in which D-glutamate monomers are joined by gamma
      peptidyl bonds. The capsule is poorly immunogenic, and efforts at exploiting the
      polymer for vaccine development have focused on increasing its inherent
      immunogenicity through chemical coupling to immune-stimulating protein carriers.
      The usual strategy has employed carbodiimide-based condensing reagents for
      activation of free alpha-carboxyl groups, despite reports that this chemistry may
      lead to chain scission. We have purified the high molecular mass capsule to >95%
      homogeneity and have demonstrated that the polymer contains >99% poly-gamma-D
      glutamic acid. The predominant structure of the polymer as assessed by circular
      dichroism and multiangle laser light scattering was unordered at near-neutral pH.
      We investigated the effects of various activation chemistries, and we
      demonstrated that carbodiimide treatment under aqueous conditions results in
      significant cleavage of the gamma-peptidyl bond, whereas scission is
      significantly reduced in nonaqueous polar solvents, although undesired side chain
      modification was still observed. An activation chemistry was developed using the
      triazine-based reagent 4-(4,6-dimethoxy (1,3,5)triazin-2-yl)-4-methylmorpholinium
      chloride, which allowed for controlled and reproducible derivatization of alpha
      carbonyls. In a two-pot reaction scheme, activated capsule was derivatized with a
      sulfhydryl-reactive heterobifunctional moiety and was subsequently coupled to
      thiolated carrier protein. This conjugate elicited very high capsule-specific
      immune titers in mice. More importantly, mice immunized with conjugated capsule
      exhibited good protection against lethal challenge from a virulent B. anthracis
      strain in two models of infection. We also showed, for the first time, that
      treatment of capsule with carbodiimide significantly reduced recognition by
      capsule-specific antisera concurrent with the reagent-induced reduction of
      polymer mass. The data suggested that for vaccine development, maintenance of the
      high mass of the polymer may be important.

PMID- 16293625
TI  - A competitive mechanism for staphylococcal toxin SSL7 inhibiting the leukocyte
      IgA receptor, Fc alphaRI, is revealed by SSL7 binding at the C alpha2/C alpha3
      interface of IgA.
AB  - Leukocyte recruitment and effector functions like phagocytosis and respiratory
      burst are key elements of immunity to infection. Pathogen survival is dependent
      upon the ability to overwhelm, evade or inhibit the immune system. Pathogenic
      group A and group B streptococci are well known to produce virulence factors that
      block the binding of IgA to the leukocyte IgA receptor, Fc alphaRI, thereby
      inhibiting IgA-mediated immunity. Recently we found Staphylococcus aureus also
      interferes with IgA-mediated effector functions as the putative virulence factor
      SSL7 also binds IgA and blocks binding to Fc alphaRI. Herein we report that SSL7
      and Fc alphaRI bind many of the same key residues in the Fc region of human IgA.
      Residues Leu-257 and Leu-258 in domain C alpha2 and residues 440-443 PLAF in C
      alpha3 of IgA lie at the C alpha2/C alpha3 interface and make major contributions
      to the binding of both the leukocyte receptor Fc alphaRI and SSL7. It is
      remarkable this S. aureus IgA binding factor and unrelated factors from
      streptococci are functionally convergent, all targeting a number of the same
      residues in the IgA Fc, which comprise the binding site for the leukocyte IgA
      receptor, Fc alphaRI.

PMID- 16293626
TI  - DNA damage promotes histone deacetylase 4 nuclear localization and repression of
      G2/M promoters, via p53 C-terminal lysines.
AB  - Repression of G(2)/M promoters after DNA damage is an active mechanism that
      requires the p53 tumor suppressor. We have recently found that histone
      deacetylase 4 (HDAC4) is recruited on NF-Y-dependent repressed promoters. In this
      report, we describe the relationship between p53 and HDAC4 recruitment following
      DNA damage using immunofluorescence, chromatin immunoprecipitation, and
      transfection experiments. HDAC4 shuttles from the cytoplasm into the nucleus,
      following DNA damage, independently of the activation of p53 and becomes
      associated with promoters through a p53-dependent mechanism. The C-terminal
      lysines of p53, which are acetylated and methylated, are required for HDAC4
      recruitment and transcriptional repression. Trichostatin treatment, but not HDAC4
      functional inactivation, relieves the adriamycin-mediated repression of G(2)/M
      promoters. Our results indicate that HDAC4 is a component of the DNA damage
      response and that post-translational modifications of p53 are important for
      repression of G(2)/M genes.

PMID- 16293627
TI  - Reuptake of extracellular amelogenin by dental epithelial cells results in
      increased levels of amelogenin mRNA through enhanced mRNA stabilization.
AB  - Amelogenin is an extracellular matrix protein secreted by ameloblasts and is a
      major component of enamel matrix. Recently, in addition to their role in enamel
      formation, the biological activity of enamel proteins in the process of cell
      differentiation has recently become widely appreciated. In this study, we
      examined the biological activity of amelogenin on ameloblast differentiation.
      Recombinant mouse amelogenin (rm-amelogenin) enhanced the expression of
      endogenous amelogenin mRNA in a cultured dental epithelial cell line (HAT-7),
      despite a lack of increased amelogenin promoter activity. To solve this
      discrepancy, we analyzed the effects of rm-amelogenin on the stability of
      amelogenin mRNA. The half-life of amelogenin mRNA is extremely short, but in the
      presence of rm-amelogenin its half-life was extended three times longer than the
      control. Furthermore, we showed the entry of exogenous fluorescein isothiocyanate
      conjugated rm-amelogenin into the cytoplasm of HAT-7 cells. It follows from our
      results that exogenous amelogenin increases amelogenin mRNA levels through
      stabilization of mRNA in the cytoplasm of HAT-7 cells. Here we speculated that
      during differentiation, dental epithelial cells utilize a unique mechanism for
      increasing the production of amelogenin, the reuptake of secreted amelogenin.

PMID- 16293628
TI  - The house dust mite allergen Der p 1, unlike Der p 3, stimulates the expression
      of interleukin-8 in human airway epithelial cells via a proteinase-activated
      receptor-2-independent mechanism.
AB  - We investigated and compared the mechanisms by which two dust mite proteolytic
      allergens, Der p 1 and Der p 3, and a peptide agonist of proteinase-activated
      receptor 2 (PAR(2)AP) trigger interleukin (IL)-8 release from human pulmonary
      epithelial cells (A549). Although all three stimuli tested induced the up
      regulation of IL-8 (mRNA and protein), the Der p 1-mediated signaling events did
      not exactly match those induced by PAR(2)AP and Der p 3. First, Der p 1 was less
      effective in stimulating IL-8 gene transcriptional activity than PAR(2)AP and Der
      p 3. Second, Der p 1-mediated IL-8 expression was mainly dependent on NF-kappaB,
      whereas Der p 3 and PAR(2)AP regulated IL-8 expression through the activation of
      both NF-kappaB and AP-1. Third, although all three MAP kinases, ERK1/2, p38, and
      JNK, were activated, Der p 1 induced IL-8 release exclusively via the ERK1/2
      signaling pathway, whereas PAR(2)AP and Der p 3 also involved the other kinases.
      Fourth, in HeLa cells, Der p 1 was able to up-regulate IL-8 secretion independent
      of PAR(2) expression, and in contrast with PAR(2)AP and Der p 3, Der p 1 was
      unable to affect calcium signaling via PAR(2) in PAR(2)-expressing KNRK cells.
      Finally, cleavage by Der p 1 of a synthetic peptide representing the N-terminal
      activation-cleavage site of PAR(2) did not release a high potency activator of
      PAR(2) as does Der p 3. We conclude that Der p 1 (but not Der p 3)-induced IL-8
      production in A549 epithelial cells is independent of PAR(2) activation.

PMID- 16293629
TI  - The Wnt-inducible transcription factor Twist1 inhibits chondrogenesis.
AB  - Wnt signaling is essential for many developmental processes, including
      skeletogenesis. To investigate the effects of Wnt signaling during skeletogenesis
      we studied the effects of Wnt on cultured chondrocytic cells and differentiating
      limb-bud mesenchyme. We showed that Wnt3a strongly repressed chondrogenesis and
      chondrocyte gene expression. Canonical Wnt signaling was responsible for the
      repression of differentiation, as evidenced by results showing that inhibition of
      glycogen synthase kinase 3 or expression of beta-catenin caused similar
      repression of differentiation. Significantly, we showed that the transcription
      repressor Twist1 is induced by canonical Wnt signaling. Expression of Twist1
      strongly inhibited chondrocyte gene expression and short hairpin RNA knockdown of
      Twist1 transcript levels caused increased expression of the chondrocyte-specific
      genes aggrecan and type II collagen. Interestingly, Twist1 interfered with BMP2
      induced expression of aggrecan and type II collagen expression and knockdown of
      Twist1 augmented BMP2-induced aggrecan and type II collagen expression. These
      data support the conclusions that Twist1 contributes to the repression of
      chondrogenesis and chondrocyte gene expression resulting from canonical Wnt
      signaling and that Twist1 interferes with BMP-dependent signaling.

PMID- 16293630
TI  - Endotoxin (lipopolysaccharide) neutralization by innate immunity host-defense
      peptides. Peptide properties and plausible modes of action.
AB  - Binding of lipopolysaccharide (LPS) to macrophages results in proinflammatory
      cytokine secretion. In extreme cases it leads to endotoxic shock. A few innate
      immunity antimicrobial peptides (AMPs) neutralize LPS activity. However, the
      underlying mechanism and properties of the peptides are not yet clear. Toward
      meeting this goal we investigated four AMPs and their fluorescently labeled
      analogs. These AMPs varied in composition, length, structure, and selectivity
      toward cells. The list included human LL-37 (37-mer), magainin (24-mer), a 15-mer
      amphipathic alpha-helix, and its D,L-amino acid structurally altered analog. The
      peptides were investigated for their ability to inhibit LPS-mediated cytokine
      release from RAW264.7 and bone marrow-derived primary macrophages, to bind LPS in
      solution, and when LPS is already bound to macrophages (fluorescence spectroscopy
      and confocal microscopy), to compete with LPS for its binding site on the CD14
      receptor (flow cytometry) and affect LPS oligomerization. We conclude that a
      strong binding of a peptide to LPS aggregates accompanied by aggregate
      dissociation prevents LPS from binding to the carrier protein lipopolysaccharide
      binding protein, or alternatively to its receptor, and hence inhibits cytokine
      secretion.

PMID- 16293631
TI  - Regulation of Gli1 localization by the cAMP/protein kinase A signaling axis
      through a site near the nuclear localization signal.
AB  - The hedgehog (Hh) pathway plays a critical role during development of embryos and
      cancer. Although the molecular basis by which protein kinase A (PKA) regulates
      the stability of hedgehog downstream transcription factor cubitus interruptus,
      the Drosophila homologue of vertebrate Gli molecules, is well documented, the
      mechanism by which PKA inhibits the functions of Gli molecules in vertebrates
      remains elusive. Here, we report that activation of PKA retains Gli1 in the
      cytoplasm. Conversely, inhibition of PKA activity promotes nuclear accumulation
      of Gli1. Mutation analysis identifies Thr374 as a major PKA site determining Gli1
      protein localization. In the three-dimensional structure, Thr374 resides adjacent
      to the basic residue cluster of the nuclear localization signal (NLS).
      Phosphorylation of this Thr residue is predicted to alter the local charge and
      consequently the NLS function. Indeed, mutation of this residue to Asp
      (Gli1/T374D) results in more cytoplasmic Gli1 whereas a mutation to Lys
      (Gli1/T374K) leads to more nuclear Gli1. Disruption of the NLS causes Gli1/T374K
      to be more cytoplasmic. We find that the change of Gli1 localization is
      correlated with the change of its transcriptional activity. These data provide
      evidence to support a model that PKA regulates Gli1 localization and its
      transcriptional activity, in part, through modulating the NLS function.

PMID- 16293632
TI  - Human TRPV4 channel splice variants revealed a key role of ankyrin domains in
      multimerization and trafficking.
AB  - The TRPV4 cation channel exhibits a topology consisting of six predicted
      transmembrane domains (TM) with a putative pore loop between TM5 and TM6 and
      intracellular N- and C-tails, the former containing at least three ankyrin
      domains. Functional transient receptor potential (TRP) channels are supposed to
      result following the assembly of four subunits. However, the rules governing
      subunit assembly and protein domains implied in this process are only starting to
      emerge. The ankyrin, TM, and the C-tail domains have been identified as important
      determinants of the oligomerization process. We now describe the maturation and
      oligomerization of five splice variants of the TRPV4 channel. The already known
      TRPV4-A and TRPV4-B (delta384-444) variants and the new TRPV4-C (delta237-284),
      TRPV4-D (delta27-61), and TRPV4-E (delta237-284 and delta384-444) variants. All
      alternative spliced variants involved deletions in the cytoplasmic N-terminal
      region, affecting (except for TRPV4-D) the ankyrin domains. Subcellular
      localization, fluorescence resonance energy transfer, co-immunoprecipitation,
      glycosylation profile, and functional analysis of these variants permitted us to
      group them into two classes: group I (TRPV4-A and TRPV4-D) and group II (TRPV4-B,
      TRPV4-C, and TRPV4-E). Group I, unlike group II variants, were correctly
      processed, homo- and heteromultimerized in the endoplasmic reticulum, and were
      targeted to the plasma membrane where they responded to typical TRPV4 stimuli.
      Our results suggest that: 1) TRPV4 biogenesis involves core glycosylation and
      oligomerization in the endoplasmic reticulum followed by transfer to the Golgi
      apparatus for subsequent maturation; 2) ankyrin domains are necessary for
      oligomerization of TRPV4; and 3) lack of TRPV4 oligomerization determines its
      accumulation in the endoplasmic reticulum.

PMID- 16293633
TI  - The AT-hook of the chromatin architectural transcription factor high mobility
      group A1a is arginine-methylated by protein arginine methyltransferase 6.
AB  - The HMGA1a protein belongs to the high mobility group A (HMGA) family of
      architectural nuclear factors, a group of proteins that plays an important role
      in chromatin dynamics. HMGA proteins are multifunctional factors that associate
      both with DNA and nuclear proteins that have been involved in several nuclear
      processes, such as transcriptional regulation, viral integration, DNA repair, RNA
      processing, and chromatin remodeling. The activity of HMGA proteins is finely
      modulated by a variety of post-translational modifications. Arginine methylation
      was recently demonstrated to occur on HMGA1a protein, and it correlates with the
      apoptotic process and neoplastic progression. Methyltransferases responsible for
      these modifications are unknown. Here we show that the protein arginine
      methyltransferase PRMT6 specifically methylates HMGA1a protein both in vitro and
      in vivo. By mass spectrometry, the sites of methylation were unambiguously mapped
      to Arg(57) and Arg(59), two residues which are embedded in the second AT-hook, a
      region critical for both protein-DNA and protein-protein interactions and whose
      modification may cause profound alterations in the HMGA network. The in vivo
      association of HMGA and PRMT6 place this yet functionally uncharacterized
      methyltransferase in the well established functional context of the chromatin
      structure organization.

PMID- 16293634
TI  - Arteriovenous fistula after renal transplantation: utility, futility or threat?

PMID- 16293635
TI  - Fulminant sclerosing peritonitis immediately following acute bacterial
      peritonitis.
AB  - Sclerosing peritonitis (SP) is an uncommon disease in the peritoneal dialysis
      population, but the considerable morbidity and mortality associated with it make
      early diagnosis and treatment imperative. We describe a case illustrating that a
      fulminant variant of SP can occur as a second phase phenomenon immediately
      following treatment of acute bacterial peritonitis, a setting in which the
      diagnosis may be masked and aggressive immunosuppression considered potentially
      hazardous. Treatment with corticosteroid alone appears particularly effective for
      SP occurring in this setting.

PMID- 16293636
TI  - Bilateral congenital megacalycosis in a young male patient.

PMID- 16293637
TI  - The K-loop, a general feature of the Pyrococcus C/D guide RNAs, is an RNA
      structural motif related to the K-turn.
AB  - The C/D guide RNAs predicted from the genomic sequences of three species of
      Pyrococcus delineate a family of small non-coding archaeal RNAs involved in the
      methylation of rRNA and tRNA. The C/D guides assemble into ribonucleoprotein
      (RNP) that contains the methyltransferase. The protein L7Ae, a key structural
      component of the RNP, binds to a Kink-turn (K-turn) formed by the C/D motif. The
      K-turn is a structure that consists of two RNA stems separated by a short
      asymmetric loop with a characteristic sharp bend (kink) between the two stems.
      The majority of the pyrococcal C/D guides contain a short 3 nt-spacer between the
      C'/D' motifs. We show here that conserved terminal stem-loops formed by the C'/D'
      motif of the Pyrococcus C/D RNAs are also L7Ae-binding sites. These stem-loops
      are related to the K-turn by sequence and structure, but they consist of a single
      stem closed by a terminal loop. We have named this structure the K-loop. We show
      that conserved non-canonical base pairs in the stem of the K-loop are necessary
      for L7Ae binding. For the C/D guides with a 3 nt-spacer we show that the sequence
      and length is also important. The K-loop could improve the stability of the C/D
      guide RNAs in Pyrococcal species, which are extreme hyperthermophiles.

PMID- 16293638
TI  - NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized
      heart failure: an international pooled analysis of 1256 patients: the
      International Collaborative of NT-proBNP Study.
AB  - AIMS: Experience with amino-terminal pro-brain natriuretic peptide (NT-proBNP)
      testing for evaluation of dyspnoeic patients with suspected acute heart failure
      (HF) is limited to single-centre studies. We wished to establish broader
      standards for NT-proBNP testing in a study involving four sites in three
      continents. METHODS AND RESULTS: Differences in NT-proBNP levels among 1256
      patients with and without acute HF and the relationship between NT-proBNP levels
      and HF symptoms were examined. Optimal cut-points for diagnosis and prognosis
      were identified and verified using bootstrapping and multi-variable logistic
      regression techniques. Seven hundred and twenty subjects (57.3%) had acute HF,
      whose median NT-proBNP was considerably higher than those without (4639 vs. 108
      pg/mL, P<0.001), and levels of NT-proBNP correlated with HF symptom severity
      (P=0.008). An optimal strategy to identify acute HF was to use age-related cut
      points of 450, 900, and 1800 pg/mL for ages <50, 50-75, and >75, which yielded
      90% sensitivity and 84% specificity for acute HF. An age-independent cut-point of
      300 pg/mL had 98% negative predictive value to exclude acute HF. Among those with
      acute HF, a presenting NT-proBNP concentration >5180 pg/mL was strongly
      predictive of death by 76 days [odds ratio=5.2, 95% confidence interval (CI)=2.2
      8.1, P<0.001]. CONCLUSION: In this multi-centre, international study, NT-proBNP
      testing was valuable for diagnostic evaluation and short-term prognosis
      estimation in dyspnoeic subjects with suspected or confirmed acute HF and should
      establish broader standards for use of the NT-proBNP in dyspnoeic patients.

PMID- 16293639
TI  - Activation of the lutropin/choriogonadotropin receptor in MA-10 cells leads to
      the tyrosine phosphorylation of the focal adhesion kinase by a pathway that
      involves Src family kinases.
AB  - We show that activation of the endogenous or recombinant
      lutropin/choriogonadotropin receptor (LHR) in mouse Leydig tumor cells (MA-10
      cells) leads to the tyrosine phosphorylation of the focal adhesion kinase (FAK)
      and one of its substrates (paxillin). Using specific antibodies to the five
      tyrosine residues of FAK that become phosphorylated, we show that activation of
      the LHR increases the phosphorylation of Tyr576 and Tyr577, but it does not
      affect the phosphorylation of Tyr397, Tyr861, or Tyr925. Because FAK is a
      prominent substrate for the Src family of tyrosine kinases (SFKs) we tested for
      their involvement in the LHR-mediated phosphorylation of FAK-Tyr576. Src is not
      detectable in MA-10 cells, but two other prominent members of this family (Fyn
      and Yes) are present. The LHR-mediated phosphorylation of FAK-Tyr576 is readily
      inhibited by PP2 (a pharmacological inhibitor of SFKs) and by dominant-negative
      mutants of SKFs. Moreover, activation of the LHR in MA-10 cells results in the
      stimulation of the activity of Fyn and Yes, and overexpression of either of these
      two tyrosine kinases enhances the LHR-mediated phosphorylation of FAK-Tyr576.
      Studies involving activation of other G protein-coupled receptors, overexpression
      of the different Galpha-subunits, and the use of second messenger analogs suggest
      that the LHR-induced phosphorylation of FAK-Tyr576 in MA-10 cells is mediated by
      SFKs, and that this family of kinases is, in turn, independently or cooperatively
      activated by the LHR-induced stimulation of Gs and Gq/11-mediated pathways.

PMID- 16293640
TI  - The genes induced by signal transducer and activators of transcription (STAT)3
      and STAT5 in mammary epithelial cells define the roles of these STATs in mammary
      development.
AB  - Prolactin and leukemia inhibitory factor (LIF) have different roles in the adult
      mammary gland, which are mediated in part by the signal transducers and
      activators of transcription (STAT)5 and STAT3. In vivo studies have shown that
      STAT5 contributes to prolactin-dependent lobuloalveolar development and lactation
      whereas STAT3 mediates LIF-dependent epithelial apoptosis during postlactational
      involution. To understand the molecular basis of these STAT-dependent pathways,
      we demonstrate the ligand-independent effects of STAT5 and STAT3 in mammary
      epithelial cells in vitro and also identify the genes regulated by these related
      transcription factors. Thus, using conditionally active STAT3- or STAT5a-GyraseB
      fusion proteins, we observed that enforced and specific dimerization of STAT3
      induced apoptosis whereas STAT5 induced differentiation of mammary epithelial
      cells. Furthermore, STAT5 attenuated apoptosis mediated by LIF, the physiological
      inducer of STAT3. Microarray analysis of STAT3- and STAT5-induced genes using
      this system demonstrated a marked specificity, which reflected their different
      physiological effects in vitro and in vivo. STAT5-specific gene targets included
      the milk protein genes alpha-casein and kallikrein-8 and the survival factors
      prosaposin and Grb10. STAT3-specific genes included the apoptosis regulators
      CCAAT enhancer binding protein-delta, phosphatidylinositol 3-kinase-regulatory
      subunits, purine nucleoside phosphorylase, and c-fos. These data illustrate that
      specific activation of STAT3 and STAT5 alone is sufficient to induce and suppress
      apoptosis, respectively, and that these transcription factors elicit their
      actions by inducing distinct subsets of target genes in mammary epithelial cells.

PMID- 16293641
TI  - Estrogen receptor (ER) beta modulates ERalpha-mediated transcriptional activation
      by altering the recruitment of c-Fos and c-Jun to estrogen-responsive promoters.
AB  - In this study, an estrogen receptor (ER) alpha-expressing T47D cell line
      containing an inducible tet-off FLAG-ERbeta was used to examine the influence of
      ERbeta on ERalpha activity. Real-time PCR analysis of mRNA levels of two well
      studied estrogen-responsive genes, pS2 and progesterone receptor (PR), showed
      that the expression levels of both genes were reduced in the presence of ERbeta.
      Chromatin immunoprecipitation assays showed that the 17beta-estradiol (E2)
      induced recruitment patterns to the pS2 and PR promoters were similar for both
      ERalpha and ERbeta. ERbeta expression did not significantly influence the kinetic
      recruitment profile of ERalpha to the pS2 promoter, but it was evident that
      ERalpha occupancy at the PR promoter was reduced. The E2-induced recruitment of c
      Fos to a 12-O-tetradecanoylphorbol-13-acetate response element site in the PR
      promoter was significantly reduced in the presence of ERbeta, whereas only a
      slight reduction in the recruitment of c-Fos to the pS2 promoter was observed.
      ERbeta expression resulted in a significant reduction in the E2-induced
      expression of c-Fos mRNA. The recruitment pattern of c-Jun was also altered by
      ERbeta, although the expression levels of c-Jun were not. Expression of ERbeta
      caused a further 30-50% decrease of the E2-induced reduction in ERalpha protein
      after 3 h of E2 treatment, showing that ERbeta influences ERalpha protein levels.
      The altered recruitment of the activating protein-1 complex, combined with the
      reduction in ERalpha protein levels, may partly explain the antagonistic effect
      of ERbeta on ERalpha-mediated transcription.

PMID- 16293642
TI  - Mouse glucose transporter 9 splice variants are expressed in adult liver and
      kidney and are up-regulated in diabetes.
AB  - A novel glucose transporter (GLUT), mouse GLUT9 (mGLUT9), was recently cloned
      from mouse 7-d embryonic cDNA. Several splice variants of mGLUT9 were described,
      two of which were cloned (mGLUT9a and mGLUT9a Delta 209-316). This study
      describes the cloning and characterization of another splice variant, mGLUT9b.
      Cloned from adult liver, mGLUT9b is identical to mGLUT9a except at the amino
      terminus. Based on analysis of the genomic structure, the different amino termini
      result from alternative transcriptional/translational start sites. Expression and
      localization of these two mGLUT9 splice variants were examined in control and
      diabetic adult mouse tissues and in cell lines. RT-PCR analysis demonstrated
      expression of mGLUT9a in several tissues whereas mGLUT9b was observed primarily
      in liver and kidney. Using a mGLUT9-specific antibody, Western blot analysis of
      total membrane fractions from liver and kidney detected a single, wide band,
      migrating at approximately 55 kDa. This band shifted to a lower molecular mass
      when deglycosylated with peptide-N-glycosidase F. Both forms were present in
      liver and kidney. Immunohistochemical localization demonstrated basolateral
      distribution of mGLUT9 in liver hepatocytes and the expression of mGLUT9 in
      specific tubules in the outer cortex of the kidney. To investigate the
      alternative amino termini, mGLUT9a and mGLUT9b were overexpressed in kidney
      epithelium cell lines. Subcellular fractions localized both forms to the plasma
      membrane. Immunofluorescent staining of polarized Madin Darby canine kidney cells
      overexpressing mGLUT9 depicted a basolateral distribution for both splice
      variants. Finally, mGLUT9 protein expression was significantly increased in the
      kidney and liver from streptozotocin-induced diabetic mice compared with
      nondiabetic animals.

PMID- 16293643
TI  - Potassium channels at the beginnings of cell proliferation.

PMID- 16293644
TI  - Motor neurone targeting of IGF-1 prevents specific force decline in ageing mouse
      muscle.
AB  - IGF-1 is a potent growth factor for both motor neurones and skeletal muscle.
      Muscle IGF-1 is known to provide target-derived trophic effects on motor
      neurones. Therefore, IGF-1 overexpression in muscle is effective in delaying or
      preventing deleterious effects of ageing in both tissues. Since age-related
      decline in muscle function stems partly from motor neurone loss, a tetanus toxin
      fragment-C (TTC) fusion protein was created to target IGF-1 to motor neurones.
      IGF-1-TTC retains IGF-1 activity as indicated by [(3)H]thymidine incorporation
      into L6 myoblasts. Spinal cord motor neurones effectively bound and internalized
      the IGF-1-TTC in vitro. Similarly, IGF-1-TTC injected into skeletal muscles was
      taken up and retrogradely transported to the spinal cord in vivo, a process
      prevented by denervation of injected muscles. Three monthly IGF-1-TTC injections
      into muscles of ageing mice did not increase muscle weight or muscle fibre size,
      but significantly increased single fibre specific force over aged controls
      injected with saline, IGF-1, or TTC. None of the injections changed muscle fibre
      type composition, but neuromuscular junction post-terminals were larger and more
      complex in muscle fibres injected with IGF-1-TTC, compared to the other groups,
      suggesting preservation of muscle fibre innervation. This work demonstrates that
      induced overexpression of IGF-1 in spinal cord motor neurones of ageing mice
      prevents muscle fibre specific force decline, a hallmark of ageing skeletal
      muscle.

PMID- 16293645
TI  - Distinct rhythm generators for inspiration and expiration in the juvenile rat.
AB  - Inspiration and active expiration are commonly viewed as antagonistic phases of a
      unitary oscillator that generates respiratory rhythm. This view conflicts with
      observations we report here in juvenile rats, where by administration of
      fentanyl, a selective mu-opiate agonist, and induction of lung reflexes, we
      separately manipulated the frequency of inspirations and expirations. Moreover,
      completely transecting the brainstem at the caudal end of the facial nucleus
      abolished active expirations, while rhythmic inspirations continued. We
      hypothesize that inspiration and expiration are generated by coupled,
      anatomically separate rhythm generators, one generating active expiration located
      close to the facial nucleus in the region of the retrotrapezoid
      nucleus/parafacial respiratory group, the other generating inspiration located
      more caudally in the preBotzinger Complex.

PMID- 16293646
TI  - Synaptotagmin-Ca2+ triggers two sequential steps in regulated exocytosis in rat
      PC12 cells: fusion pore opening and fusion pore dilation.
AB  - Synaptotagmin I (Syt I), the putative Ca(2+) sensor in regulated exocytosis, has
      two Ca(2+)-binding modules, the C2A and C2B domains, and a number of putative
      effectors to which Syt I binds in a Ca(2+)-dependent fashion. The role of Ca(2+)
      binding to these domains remains unclear, as efforts to address questions about
      Ca(2+)-triggered effector interactions have led to conflicting results. We have
      studied the effects of Ca(2+) on fusion pores using amperometry to follow the
      exocytosis of single vesicles in real time and analyse the kinetics of fusion
      pore transitions. Elevating [Ca(2+)] in permeabilized cells reduced the fusion
      pore lifetime, indicating an action of Ca(2+) during the actual fusion process.
      Analysing the Ca(2+) dependence of the fusion pore lifetime, together with the
      frequency of pore openings and the proportion of openings that close without
      dilating (kiss-and-run events) enabled us to resolve exocytosis into a sequence
      of kinetic steps representing functional transitions in the fusion pore. Fusion
      pore opening and dilation were both accelerated by Ca(2+), indicating separate
      Ca(2+) control over each of these steps. Ca(2+) ligand mutations in either the
      C2A or C2B domains of Syt I reduced fusion pore opening, but had opposite actions
      on the rate of fusion pore closure. These studies resolve two separate and
      distinct Ca(2+)-triggered steps during regulated exocytosis. The C2A and C2B
      domains of Syt I have different actions during these steps, and these actions may
      be linked to their distinctive effector interactions.

PMID- 16293647
TI  - A differential role for nitric oxide in two forms of physiological angiogenesis
      in mouse.
AB  - NO plays a role in a variety of in vitro models of angiogenesis, although
      confounding effects of NO on non-endothelial tissues make its role during in vivo
      angiogenesis unclear. We therefore examined the effects of NO on two
      physiological models of angiogenesis in mouse skeletal muscle: (1) administration
      of prazosin (50 mg l-1) thereby increasing blood flow; and (2) muscle overload
      from surgical ablation of a functional synergist. These models induce
      angiogenesis via longitudinal splitting and capillary sprouting, respectively.
      Administration of NG-nitro-L-arginine (L-NNA) abolished the increase in capillary
      to fibre ratio (C:F) in response to prazosin administration, along with the
      increases in luminal filopodia and large endothelial vacuoles. L-NNA prevented
      luminal filopodia and vacuolisation in response to extirpation, but had no effect
      on abluminal sprouting, and little effect on C:F. Comparison of mice lacking
      endothelial (eNOS-/-) and neuronal NO synthase (nNOS-/-) showed that longitudinal
      splitting is eNOS-dependent, and Western blotting demonstrated an increase in
      eNOS but not inducible NOS (iNOS) expression. These data show that there are two
      pathways of physiological angiogenesis in skeletal muscle characterised by
      longitudinal splitting and capillary sprouting, respectively. NO generated by
      eNOS plays an essential role in splitting but not in sprouting angiogenesis,
      which has important implications for angiogenic therapies that target NO.

PMID- 16293648
TI  - Hypospadias: a transgenerational effect of diethylstilbestrol?
AB  - BACKGROUND: In 2002, an increased risk of hypospadias was reported for sons of
      women exposed to diethylstilbestrol (DES) in utero, suggesting transgenerational
      effects of DES. The aim of this study was to further assess the association
      between parental DES exposure and hypospadias in a case-referent study. METHODS:
      Cases with hypospadias were retrieved from the hospital information system.
      Referents were recruited via the parents of cases. Both parents completed postal
      questionnaires. Associations were estimated by odds ratios (OR) with 95%
      confidence intervals (CI). Additionally, conditional logistic regression analyses
      were performed for a matched subset of parents. RESULTS: The final database
      included 583 cases and 251 referents. In the initial analyses, an indication was
      found for an increased risk of hypospadias when mothers were exposed to DES in
      utero: OR=2.3 (95% CI 0.7-7.9). Conditional logistic regression resulted in a
      stronger risk estimate: OR=4.9 (95% CI 1.1-22.3). Paternal exposure to DES did
      not increase the risk. CONCLUSIONS: The results confirm an increased risk of
      hypospadias when mothers were exposed to DES in utero. However, the excess risk
      appears to be of much smaller magnitude than in the 2002 study. Further research
      on the potential health risks for the third generation is of great importance.

PMID- 16293650
TI  - Quantification of endometriotic lesions in a murine model by fluorimetric and
      morphometric analyses.
AB  - BACKGROUND: In animal models of endometriosis, the identification and
      quantification of lesions originating from human endometrium is often hampered by
      the small size of the implants and their embedding in murine tissue. The purpose
      of the present study was to develop two new methods of quantifying endometriosis
      like lesions in a nude mouse model: fluorimetry and morphometry. METHODS: Human
      menstrual endometrium was labelled using a fluorescent tracker,
      carboxyfluorescein diacetate, succinimidyl ester (CFDA-SE), and transplanted into
      the pelvic cavity of mice by injection through the peritoneum after performing a
      cutaneous incision. After 5 days, lesions were recovered by laparotomy. The
      fluorescence of the recovered endometriotic lesions was measured. Endometrial
      stroma and glands were immunostained in lesion sections with anti-CD10 and anti
      CK22 antibodies, and their surface area was evaluated by morphometric analysis.
      RESULTS: Fluorescent labelling allows identification of lesions not visible
      macroscopically. A good correlation was observed between fluorimetry and
      morphometry (r=0.88) applied for lesion quantification. CONCLUSIONS: Fluorimetric
      evaluation combined with morphometric analysis of endometriosis-like lesions
      allows objective and reliable recording of endometriosis development in a nude
      mouse model. This quantification method could therefore be useful for future
      pharmacological and toxicological studies.

PMID- 16293649
TI  - Single nucleotide polymorphisms of the gonadotrophin-regulated testicular
      helicase (GRTH) gene may be associated with the human spermatogenesis impairment.
AB  - BACKGROUND: Gonadotropin-regulated testicular RNA helicase (GRTH) is a testis
      specific RNA helicase that is essential for completion of spermatogenesis and is
      involved in pathogenesis of impaired spermatogenesis in mouse. It is therefore
      reasonable to postulate that human GRTH gene may also play a role in impaired
      spermatogenesis in humans. To test this hypothesis, we investigated the possible
      association between the variations of the GRTH gene and human spermatogenesis
      impairment. METHODS: Mutation screening of exons and intron/exon boundaries of
      GRTH gene was carried out by denaturing high-performance liquid chromatography
      (DHPLC) in 347 infertile patients with idiopathic azoospermia and severe
      oligozoospermia as well as 201 fertile men. RESULTS: Four single nucleotide
      polymorphisms (SNP), namely IVS6+55G-->T, ISV8+10A-->C, c.852C-->T and c.927G-
      >A, were identified. Among them, significant differences in polymorphism
      frequencies were observed at the polymorphic IVS6+55G-->T and c.852C-->T loci
      between the patients and controls, and a significant association between
      haplotypes of these two loci and male infertility with impaired spermatogenesis
      was detected. CONCLUSIONS: Results of the present study indicate that SNP
      IVS6+55G-->T and c.852C-->T of GRTH gene may be associated with male infertility
      with azoospermia or severe oligozoospermia, suggesting that variations in GRTH
      gene may contribute to susceptibility to spermatogenic impairment in humans.

PMID- 16293651
TI  - Fertility awareness, intentions concerning childbearing, and attitudes towards
      parenthood among female and male academics.
AB  - BACKGROUND: Postponing childbirth is becoming increasingly common in Western
      countries, especially among groups with higher education qualifications. It is
      relatively unknown to what extent women and men are aware of the age-related
      decline in female fertility. The aim was to investigate university students'
      intentions and attitudes to future parenthood and their awareness regarding
      female fertility. METHODS: Postal survey of a randomly selected sample of 222
      female (74% response) and 179 male (60% response) university students. RESULTS:
      Female and male university students in Sweden have largely positive attitudes
      towards parenthood and want to have children. Women, in comparison to men, were
      significantly more concerned about problems related to combining work and
      children. Both women and men had overly optimistic perceptions of women's chances
      of becoming pregnant. About half of women intended to have children after age 35
      years and were not sufficiently aware of the age-related decline of female
      fecundity in the late 30s. CONCLUSIONS: University students plan to have children
      at ages when female fertility is decreased without being sufficiently aware of
      the age-related decline in fertility. This increases the risk of involuntary
      infertility in this group, which is alarming in view of the great importance they
      put on parenthood.

PMID- 16293652
TI  - Methane, a gas produced by enteric bacteria, slows intestinal transit and
      augments small intestinal contractile activity.
AB  - The presence of methane on lactulose breath test among irritable bowel syndrome
      (IBS) subjects is highly associated with the constipation-predominant form.
      Therefore, we set out to determine whether methane gas can alter small intestinal
      motor function. In dogs, small intestinal fistulae were created to permit
      measurement of intestinal transit. Using a radiolabel, we evaluated transit
      during infusion of room air and subsequently methane. In this model, small
      intestinal infusion of methane produced a slowing of transit in all dogs by an
      average of 59%. In a second experiment, guinea pig ileum was pinned into an organ
      bath for the study of contractile activity in response to brush strokes applied
      to the mucosa. The force of contraction was measured both orad and aborad to the
      stimulus. The experiment was repeated while the bath was gassed with methane.
      Contractile activities orad and aborad to the stimulus were significantly
      augmented by methane compared with room air (P < 0.05). In a third experiment,
      humans with IBS who had undergone a small bowel motility study were compared such
      that subjects who produced methane on lactulose breath test were compared with
      those producing hydrogen. The motility index was significantly higher in methane
      producing IBS patients (1,851 +/- 861) compared with hydrogen producers (1,199 +/
      301) (P < 0.05). Therefore, methane, a gaseous by-product of intestinal
      bacteria, slows small intestinal transit and appears to do so by augmenting small
      bowel contractile activity.

PMID- 16293653
TI  - VEGF-A stimulation of leukocyte adhesion to colonic microvascular endothelium:
      implications for inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory disorder characterized
      by increased leukocyte recruitment and subsequent tissue damage. An increase in
      the density of the microvasculature of the colon during IBD has been suggested,
      leading to the concept that angiogenesis may play a pathological role in IBD.
      Increased tissue and serum levels of the angiogenic cytokine VEGF-A have been
      reported in cases of active IBD. In this study, we examined the hypothesis that
      VEGF-A exerts a proinflammatory effect on colon microvascular endothelium that
      contributes to colonic inflammation. Leukocyte adhesion to VEGF-A-stimulated
      colon microvascular endothelial cells was examined using a parallel-plate
      hydrodynamic flow chamber. ICAM-1 adhesion molecule expression on colonic
      microvascular endothelium also was determined in response to VEGF-A stimulation,
      along with characterization of leukocyte adhesion molecule expression. High-dose
      VEGF-A (50 ng/ml) stimulation increased neutrophil and T cell adhesion to and
      decreased rolling velocities on activated endothelium, whereas low-dose VEGF-A
      (10 ng/ml) was without effect. Colonic endothelium constitutively expressed ICAM
      1, which was significantly increased by treatment with 50 ng/ml VEGF-A or 10
      ng/ml TNF-alpha but not 10 ng/ml VEGF-A. T cells expressed CD18 and CD11a with no
      expression of CD11b, whereas neutrophils expressed CD18, CD11a, and CD11b.
      Finally, VEGF-A-dependent leukocyte adhesion was found to occur in a CD18
      dependent manner. These results demonstrate that VEGF-A levels found in IBD exert
      a proinflammatory effect similar to other inflammatory agents and suggest that
      this cytokine may serve as an intermediary between angiogenic stimulation and
      cell-mediated immune responses.

PMID- 16293654
TI  - Effects of pancreatic duct ligation on pancreatic response to bombesin.
AB  - To examine mechanisms that might be related to biliary pancreatitis, we examined
      the effects of pancreatic duct ligation (PDL) with pancreatic stimulation in
      vivo. PDL alone caused no increase in pancreatic levels of trypsinogen activation
      peptide (TAP), trypsin, or chymotrypsin and did not initiate pancreatitis.
      Although bombesin caused zymogen activation within the pancreas, the increases
      were slight and it did not cause pancreatitis. However, the combination of PDL
      with bombesin resulted in prominent increases in pancreatic TAP, trypsin,
      chymotrypsin, and the appearance of TAP in acinar cells and caused pancreatitis.
      Disruption of the apical actin network in the acinar cell was observed when PDL
      was combined with bombesin but not with PDL or bombesin alone. These studies
      suggest that when PDL is combined with pancreatic acinar cell stimulation, it can
      promote zymogen activation, the retention of active enzymes in acinar cells, and
      the development of acute pancreatitis.

PMID- 16293655
TI  - Spontaneous electrical rhythmicity and the role of the sarcoplasmic reticulum in
      the excitability of guinea pig gallbladder smooth muscle cells.
AB  - Spontaneous action potentials and Ca(2+) transients were investigated in intact
      gallbladder preparations to determine how electrical events propagate and the
      cellular mechanisms that modulate these events. Rhythmic phasic contractions were
      preceded by Ca(2+) flashes that were either focal (limited to one or a few
      bundles), multifocal (occurring asynchronously in several bundles), or global
      (simultaneous flashes throughout the field). Ca(2+) flashes and action potentials
      were abolished by inhibiting sarcoplasmic reticulum (SR) Ca(2+) release via
      inositol (1,4,5)-trisphosphate [Ins(1,4,5)P(3)] channels with 2
      aminoethoxydiphenyl borate and xestospongin C or by inhibiting voltage-dependent
      Ca(2+) channels (VDCCs) with nifedipine or diltiazem or nisoldipine. Inhibiting
      ryanodine channels with ryanodine caused multiple spikes superimposed upon
      plateaus of action potentials and extended quiescent periods. Depletion of SR
      Ca(2+) stores with thapsigargin or cyclopiazonic acid increased the frequency and
      duration of Ca(2+) flashes and action potentials. Acetylcholine, carbachol, or
      cholecystokinin increased synchronized and increased the frequency of Ca(2+)
      flashes and action potentials. The phospholipase C (PLC) inhibitor U-73122 did
      not affect Ca(2+) flash or action potential activity but inhibited the excitatory
      effects of acetylcholine on these events. These results indicate that Ca(2+)
      flashes correspond to action potentials and that rhythmic excitation in the
      gallbladder is multifocal among gallbladder smooth muscle bundles and can be
      synchronized by excitatory agonists. These events do not depend on PLC
      activation, but agonist stimulation involves activation of PLC. Generation of
      these events depends on Ca(2+) entry via VDCCs and on Ca(2+) mobilization from
      the SR via Ins(1,4,5)P(3) channels.

PMID- 16293656
TI  - Mechanosensory properties in the human gastric antrum evaluated using B-mode
      ultrasonography during volume-controlled antral distension.
AB  - The aims of this study were to evaluate gastric antral mechanical behavior and
      distension-induced sensorimotor responses in the human gastric antrum using
      transabdominal ultrasound scanning. Ten healthy volunteers underwent volume
      controlled ramp inflation of a bag located in the antrum with volumes up to 125
      ml. The active and passive circumferential tensions and stresses were calculated
      from measurements of pressure, diameter, and wall thickness before and during the
      administration of the anticholinergic drug butylscopolamine. The bag distensions
      elicited contractions in the antrum and sensory responses below the pain
      threshold. Butylscopolamine abolished the contractions and significantly reduced
      the sensory response. The length-tension diagram known from in vitro studies of
      smooth muscle strips could be reproduced as tension-volume diagrams in the human
      gastric antrum. The number of induced contractions and the contraction pressure
      amplitude (afterload) showed a parabolic behavior as function of the distension
      volume (preload), with maximum approximately at 70 ml. At the sensation
      threshold, the luminal circumference showed the lowest variation coefficient (13
      25%), whereas the variation coefficient was more than 100% for the pressure,
      tensions, and stresses. We conclude that the muscle length-tension diagram and
      typical preload-afterload curves ad modem the Frank-Starling cardiac law can be
      obtained in the human gastric antrum. The sensory responses were most closely
      associated with the luminal circumference, indicating that the sensation during
      antral distension depends on deformation rather than on tension.

PMID- 16293657
TI  - Differential cytokine response from dendritic cells to commensal and pathogenic
      bacteria in different lymphoid compartments in humans.
AB  - Resident host microflora condition and prime the immune system. However, systemic
      and mucosal immune responses to bacteria may be divergent. Our aim was to
      compare, in vitro, cytokine production by human mononuclear and dendritic cells
      (DCs) from mesenteric lymph nodes (MLNs) and peripheral blood mononuclear cells
      (PBMCs) to defined microbial stimuli. Mononuclear cells and DCs isolated from the
      MLN (n = 10) and peripheral blood (n = 12) of patients with active colitis were
      incubated in vitro with the probiotic bacteria Lactobacillus salivarius UCC118 or
      Bifidobacterium infantis 35624 or the pathogenic organism Salmonella typhimurium
      UK1. Interleukin (IL)-12, tumor necrosis factor (TNF)-alpha, transforming growth
      factor (TGF)-beta, and IL-10 cytokine levels were quantified by ELISA. PBMCs and
      PBMC-derived DCs secreted TNF-alpha in response to the Lactobacillus,
      Bifidobacteria, and Salmonella strains, whereas MLN cells and MLN-derived DCs
      secreted TNF-alpha only in response to Salmonella challenge. Cells from the
      systemic compartment secreted IL-12 after coincubation with Salmonella or
      Lactobacilli, whereas MLN-derived cells produced IL-12 only in response to
      Salmonella. PBMCs secreted IL-10 in response to the Bifidobacterium strain but
      not in response to the Lactobacillus or Salmonella strain. However, MLN cells
      secreted IL-10 in response to Bifidobacteria and Lactobacilli but not in response
      to Salmonella. In conclusion, commensal bacteria induced regulatory cytokine
      production by MLN cells, whereas pathogenic bacteria induce T cell helper 1
      polarizing cytokines. Commensal-pathogen divergence in cytokine responses is more
      marked in cells isolated from the mucosal immune system compared with PBMCs.

PMID- 16293658
TI  - Possible involvement of organic anion transporting polypeptide 1c1 in the
      photoperiodic response of gonads in birds.
AB  - The photoperiodic response of the gonads requires T3, which is generated
      photoperiodically from T4 by type 2 iodothyronine deiodinase in the hypothalamus.
      Although thyroid hormones were long thought to traverse the plasma membrane by
      passive diffusion due to their lipophilic nature, it is now known that several
      organic anion transporting polypeptides (Oatp) transport thyroid hormones into
      target cells. In this study, we have used database searches to isolate DNA
      sequences encoding members of the chicken Oatp family and constructed a molecular
      phylogenetic tree. Comprehensive expression analyses using in situ hybridization
      revealed strong expression of cOatp1c1 and weak expression of cOatp1b1 in the
      ventro-lateral walls of basal tuberal hypothalamus, whereas expression of four
      genes (cOatp1a1, cOatp1b1, cOatp1c1, and cOatp3a2) was observed in the choroid
      plexus. Expression levels of all these genes in both regions were not different
      between short-day and long-day conditions. Functional expression of cOatp1c1 in
      Chinese hamster ovary cells revealed that cOatp1c1 is a highly specific
      transporter for T4 with an apparent Km of 6.8 nm and a Vmax of 1.50 pmol per
      milligram of protein per minute. These results suggest that cOatp1c1 could be
      involved in the thyroxine transport necessary for the avian photoperiodic
      response of the gonads.

PMID- 16293659
TI  - Development of a panel of monoclonal antibodies against the mineralocorticoid
      receptor.
AB  - Mineralocorticoid receptors (MR) bind both mineralocorticoids and
      glucocorticoids. They are expressed in multiple tissues and mediate diverse
      functions. Less is known about MR regulation and function compared with other
      major steroid receptors, although its importance has become increasingly
      apparent. A significant obstacle to such studies has been the dearth of specific
      high-affinity MR antibodies. We have produced monoclonal antibodies against 10
      different peptide conjugates, six from the N terminus (A/B domain) and four from
      the C terminus (steroid binding domain), with the anticipation that their
      individual affinities for the MR would differ depending upon its conformation,
      which in turn, is dependent upon the location of the receptor within the cell and
      the proteins associated with it. Hybridoma clones with high titers to the cognate
      peptide ELISA were analyzed by Western blots using protein from Chinese hamster
      ovary cells transfected with enhanced green fluorescent protein-rat MR cDNA and
      from hippocampal cytosol from adrenalectomized rats. Immunohistochemistry was
      done on kidney, heart, colon, and brain. Antibodies that proved to be most useful
      for Western blot analysis and immunohistochemistry include those raised against
      peptides comprising amino acids 1-18, 64-82, 79-97, and 365-381. The intensity of
      immunoreactivity in the cytosol compared with nucleus in the same cells differed
      between antibodies, suggesting that certain receptor epitopes were more or less
      exposed depending on the location of the receptor within the cell. In summary,
      several antibodies are described that recognize different parts of the MR that
      should facilitate the study of this important mediator of two classes of steroid
      hormone action.

PMID- 16293660
TI  - Estrogen up-regulates inducible nitric oxide synthase, nitric oxide, and
      cyclooxygenase-2 in splenocytes activated with T cell stimulants: role of
      interferon-gamma.
AB  - Estrogen is implicated in many autoimmune diseases and is a robust
      immunomodulator. For example, it regulates interferon (IFN)-gamma, a cytokine
      believed to up-regulate inducible nitric oxide synthase (iNOS). A notable gap in
      the literature is a lack of information on the regulation of nitric oxide in
      immune tissues by estrogen. We now show that activation of splenocytes with T
      cell stimulants [concanavalin-A (Con-A) or anti-CD3 antibodies] results in
      copious release of nitric oxide in splenocyte cultures from estrogen-treated but
      not placebo-treated mice. Moreover, even a low dose of T cell stimulants induced
      nitric oxide in splenocytes from estrogen-treated, but not placebo-treated, mice.
      Con-A-activated splenocytes from estrogen-treated mice also have up-regulated
      iNOS mRNA, iNOS protein, and cyclooxygenase-2 (a nitric oxide-regulated
      downstream proinflammatory protein) when compared with controls. Our studies
      suggest that the induction of nitric oxide by activated splenocytes from estrogen
      treated mice is mediated in part by IFNgamma. First, blocking costimulatory
      signals mediated through interactions of CD28 and B7 molecules by CTLA-4Ig
      markedly decreased not only IFNgamma but also nitric oxide. Second, estrogen
      treatment of IFNgamma-knockout (IFNgamma(-)/(-)) mice did not induce iNOS protein
      or nitric oxide. Finally, in vitro addition of recombinant IFNgamma to Con-A
      activated splenocytes from IFNgamma((-)/(-)) mice induced iNOS protein primarily
      in estrogen-treated mice. Overall, this is the first report to show that estrogen
      treatment up-regulates IFNgamma-inducible-iNOS gene expression, iNOS protein,
      nitric oxide, and cyclooxygenase-2 as an indirect consequence of activation of T
      cells. These findings may have wide implications to immunity and inflammatory
      disorders including female-predominant autoimmune diseases.

PMID- 16293661
TI  - A carboxyl leucine-rich region of parathyroid hormone-related protein is critical
      for nuclear export.
AB  - PTHrP is an oncofetal protein with distinct proliferative and antiapoptotic roles
      that are affected by nucleocytoplasmic shuttling. The protein's nuclear export is
      sensitive to leptomycin B, consistent with a chromosome region maintenance
      protein 1-dependent pathway. We determined that the 109-139 region of PTHrP was
      involved in its nuclear export by demonstrating that a C-terminal truncation
      mutant, residues 1-108, exports at a reduced rate, compared with the wild-type
      139 amino acid isoform. We searched for potential nuclear export sequences within
      the 109-139 region, which is leucine rich. Comparisons with established nuclear
      export sequences identified a putative consensus signal at residues 126-136.
      Deletion of this region resulted in nuclear export characteristics that closely
      matched those of the C-terminal truncation mutant. Confocal microscopic analyses
      of transfected 293, COS-1, and HeLa cells showed that steady-state nuclear levels
      of the truncated and deletion mutants were significantly greater than levels of
      wild-type PTHrP and were unaffected by leptomycin B, unlike the wild-type
      protein. In addition, both mutants demonstrated greatly reduced nuclear export
      with assays using nuclear preparations and intact cells. Based on these results,
      we conclude that the 126-136 amino acid sequence closely approximates the
      structure of a chromosome region maintenance protein 1-dependent leucine-rich
      nuclear export signal and is critical for nuclear export of PTHrP.

PMID- 16293663
TI  - Colocalization of kisspeptin and gonadotropin-releasing hormone in the ovine
      brain.
AB  - Kisspeptin is a peptide that has been implicated in the regulation of GnRH cells
      in the brain. Immunohistochemical studies were undertaken to examine the
      distribution of kisspeptin-immunoreactive (IR) cells in the ovine diencephalon
      and determine the effect of ovariectomy in the ewe. We report that kisspeptin
      colocalizes to a high proportion of GnRH-IR cells in the preoptic area, which is
      a novel finding. A high level of colocalization of kisspeptin and GnRH was also
      seen in varicose neuronal fibers within the external, neurosecretory zone of the
      median eminence. Apart from the kisspeptin/GnRH cells, a population of single
      labeling kisspeptin-IR cells was also observed in the preoptic area. Within the
      hypothalamus, kisspeptin-IR cells were found predominantly in the arcuate
      nucleus, and there was an increase in the number of immunohistochemically
      identified cell within this nucleus after ovariectomy. Kisspeptin-IR cells were
      also found in the periventricular nucleus of the hypothalamus, but the number
      observed was similar in gonad-intact and ovariectomized ewes. The colocalization
      of GnRH and kisspeptin within cells of the preoptic area and GnRH neurosecretory
      terminals of the median eminence suggests that the two peptides might be
      cosecreted into the hypophyseal portal blood to act on the pituitary gland.
      Effects of ovariectomy on the non-GnRH, Kisspeptin-IR cells of the hypothalamus
      suggest that kisspeptin production is negatively regulated by ovarian steroids.

PMID- 16293662
TI  - Gonadotropin-inhibitory hormone inhibits gonadal development and maintenance by
      decreasing gonadotropin synthesis and release in male quail.
AB  - Until recently, any neuropeptide that directly inhibits gonadotropin secretion
      had not been identified. We recently identified a novel hypothalamic
      dodecapeptide that directly inhibits gonadotropin release in quail and termed it
      gonadotropin-inhibitory hormone (GnIH). The action of GnIH on the inhibition of
      gonadotropin release is mediated by a novel G protein-coupled receptor in the
      quail pituitary. This new gonadotropin inhibitory system is considered to be a
      widespread property of birds and provides us with an unprecedented opportunity to
      study the regulation of avian reproduction from an entirely novel standpoint. To
      understand the physiological role(s) of GnIH in avian reproduction, we
      investigated GnIH actions on gonadal development and maintenance in male quail.
      Continuous administration of GnIH to mature birds via osmotic pumps for 2 wk
      decreased the expressions of gonadotropin common alpha and LHbeta subunit mRNAs
      in a dose-dependent manner. Plasma LH and testosterone concentrations were also
      decreased dose dependently. Furthermore, administration of GnIH to mature birds
      induced testicular apoptosis and decreased spermatogenic activity in the testis.
      In immature birds, daily administration of GnIH for 2 wk suppressed normal
      testicular growth and rise in plasma testosterone concentrations. An inhibition
      of juvenile molt also occurred after GnIH administration. These results indicate
      that GnIH inhibits gonadal development and maintenance through the decrease in
      gonadotropin synthesis and release. GnIH may explain the phenomenon of
      photoperiod-induced gonadal regression before an observable decline in
      hypothalamic GnRH in quail. To our knowledge, GnIH is the first identified
      hypothalamic neuropeptide inhibiting reproductive function in any vertebrate
      class.

PMID- 16293664
TI  - Maintenance of gonadotropin secretion by glucocorticoids under stress conditions
      through the inhibition of prostaglandin synthesis in the brain.
AB  - We have previously reported that glucocorticoids counteract the suppressive
      effects of tumor necrosis factor-alpha on both pulsatile and surge secretion of
      LH. This suggests that glucocorticoids have a protective effect on reproductive
      function under infectious stress. In the present study, we examined whether
      glucocorticoids maintain pulsatile LH secretion under various conditions of acute
      stress and the possible involvement of prostaglandins (PGs) in glucocorticoid
      actions. Three different types of stressors, namely infectious
      (lipopolysaccharide, 0.5 microg/kg), hypoglycemic (2-deoxy-D-glucose, 100 mg/kg),
      and restraint stress (1 h) were applied to ovariectomized rats. In ovariectomized
      rats, LH pulses were partially suppressed by restraint, but not by
      lipopolysaccharide or 2-deoxy-D-glucose. On the other hand, adrenalectomy (ADX)
      significantly enhanced the suppressive effects of all the stressors applied on LH
      pulses. Treatment with both corticosterone (25 mg/kg) and indomethacin (10 mg/kg)
      in ADX rats significantly attenuated the suppressive effects of these stressors
      on LH pulses. In addition, the immunoreactivity of cyclooxygenase-2, a PG
      synthesizing enzyme, in the brain under stress conditions was much enhanced by
      ADX, and this was counteracted by corticosterone treatment. Similarly, an
      increase in body temperature under restraint stress was enhanced by ADX and
      suppressed by corticosterone. These results suggest that suppression of LH
      pulsatility by stress is mediated by PGs in the brain, and that increased release
      of endogenous glucocorticoids in response to stress counteracts this suppression
      by inhibiting PG synthesis, and thereby maintains reproductive function
      regardless of the nature of the stressor.

PMID- 16293665
TI  - Gonadotropin-releasing hormone-expressing neurons immortalized conditionally are
      activated by insulin: implication of the mitogen-activated protein kinase
      pathway.
AB  - Energy balance exerts a critical influence on reproduction via changes in the
      circulating levels of hormones such as insulin. This modulation of the
      neuroendocrine reproductive axis ultimately involves variations in the activity
      of hypothalamic neurons expressing GnRH. Here we studied the effects of insulin
      in primary hypothalamic cell cultures as well as a GnRH neuronal cell line that
      we generated by conditional immortalization of adult hypothalamic neurons. These
      cells, which represent the first successful conditional immortalization of GnRH
      neurons, retain many of their mature phenotypic characteristics. In addition, we
      show that they express the insulin receptor. Consistently, their stimulation with
      insulin activates both the phosphatidylinositol 3-kinase and the Erk1/2 MAPK
      signaling pathways and stimulates a rapid increase in the expression of c-fos,
      demonstrating their responsiveness to this hormone. Further work performed in
      parallel in immortalized GnRH-expressing cells and primary neuronal cultures
      containing non-GnRH-expressing neurons shows that insulin induces the expression
      of GnRH in both models. In primary cultures, inhibition of the Erk1/2 pathway
      abolishes the stimulation of GnRH expression by insulin, whereas blockade of the
      phosphatidylinositol 3-kinase pathway has no effect. In conclusion, these data
      strongly suggest that GnRH neurons are directly sensitive to insulin and
      implicate for the first time the MAPK Erk1/2 signaling pathway in the central
      effects of insulin on the neuroendocrine reproductive axis.

PMID- 16293666
TI  - Dehydroepiandrosterone sulfate is neuroprotective when administered either before
      or after injury in a focal cortical cold lesion model.
AB  - Dehydroepiandrosterone and its sulfate (DHEAS) are sex hormone precursors that
      exert marked neurotrophic and/or neuroprotective activity in the central nervous
      system. The present study evaluated the effects of DHEAS and 17beta-estradiol
      (E2) in a focal cortical cold lesion model, in which DHEAS (50 mg/kg, sc) and E2
      (35 mg/kg, sc) were administered either as pretreatment (two subsequent
      injections 1 d and 1 h before lesion induction) or posttreatment (immediately
      after lesion induction). The focal cortical cold lesion was induced in the
      primary motor cortex by means of a cooled copper cylinder placed directly onto
      the cortical surface. One hour later, the animals were killed, the brains cut
      into 0.4-mm-thick slices, and the sections stained with 1% triphenyltetrazolium
      chloride. The volume of the hemispheric lesion was calculated for each animal.
      The results demonstrated that the lesion area was significantly attenuated in
      both the DHEAS- and E2- pre- and posttreated groups and that in the presence of
      letrozole, a nonsteroidal aromatase inhibitor, no neuroprotection was observed,
      suggesting that the beneficial effect of DHEAS on the cold injury might depend on
      the conversion of DHEAS to E2 within the brain. It is concluded that even a
      single posttraumatic administration of DHEAS may be of substantial therapeutic
      benefit in the treatment of focal brain injury with vasogenic edema.

PMID- 16293667
TI  - Elevated circulating insulin-like growth factor binding protein-1 is sufficient
      to cause fetal growth restriction.
AB  - IGF binding protein-1 (IGFBP-1) inhibits the mitogenic actions of the IGFs.
      Circulating IGFBP-1 is elevated in newborns and experimental animals with fetal
      growth restriction (FGR). To establish a causal relationship between high
      circulating IGFBP-1 and FGR, we have generated transgenic mice using the mouse
      alpha-fetoprotein gene promoter to target overexpression of human IGFBP-1 (hIGFBP
      1) in the fetal liver. These transgenic mice (AFP-BP1) expressed hIGFBP-1 mainly
      in the fetal hepatocytes, starting at embryonic d 14.5 (E14.5), with lower levels
      in the gut. The expression peaked at 1 wk postnatally (plasma concentration, 474
      +/- 34 ng/ml). At birth, AFP-BP1 pups were 18% smaller [weighed 1.34 +/- 0.02 g
      compared with 1.62 +/- 0.04 g for wild type (WT); P < 0.05], and they did not
      demonstrate any postnatal catch-up growth. The placentas of the AFP-BP1 mice were
      larger than WT from E16.5 onwards (150 +/- 12 for AFP-BP1 vs. 100 +/- 5 mg for WT
      at E16.5; P < 0.05). Thus, this model of FGR is associated with a larger
      placenta, but without postnatal catch-up growth. Overall, these data clearly
      demonstrate that high concentrations of circulating IGFBP-1 are sufficient to
      cause FGR.

PMID- 16293668
TI  - Forebrain gonadotropin-releasing hormone neuronal development: insights from
      transgenic medaka and the relevance to X-linked Kallmann syndrome.
AB  - Neurons that synthesize and release GnRH are essential for the central regulation
      of reproduction. Evidence suggests that forebrain GnRH neurons originate in the
      olfactory placode and migrate to their final destinations, although this is still
      a matter of controversy. X-linked Kallmann syndrome (X-KS), characterized by
      failed gonadal function secondary to deficient gonadotropin secretion, is caused
      by a mutation in KAL1, which is suggested to regulate the migration of forebrain
      GnRH neurons. Because rodents lack Kal1 in their genome and have GnRH neurons
      scattered throughout their forebrain, the development of forebrain GnRH neurons
      and the pathogenesis of X-KS have been difficult to study. In the present study,
      we generated transgenic medaka that expressed green fluorescent protein under the
      control of the gnrh1 and gnrh3 promoters for analyzing forebrain GnRH neuronal
      development. Our data revealed the presence of the following four gnrh1 neuronal
      populations: an olfactory region-derived ventral preoptic population, a dorsal
      preoptic population that migrates from the dorsal telencephalon, a medial ventral
      telencephalic population that migrates from the anterior telencephalon, and a
      nonmigratory ventral hypothalamic population. We found that all forebrain gnrh3
      neurons, extending from the terminal nerve ganglion to the anterior
      mesencephalon, arise from the olfactory region and that trigeminal ganglion
      neurons express gnrh3. Maternal gnrh3 expression was also observed in oocytes and
      early embryos. We subsequently identified a KAL1 ortholog and its paralogous form
      in the medaka. Consistent with the X-KS phenotype, antisense knockdown of the
      medaka KAL1 ortholog resulted in the disruption of forebrain GnRH neuronal
      migration. Thus, these transgenic medaka provide a useful model system for
      studying GnRH neuronal development and disorders of GnRH deficiency.

PMID- 16293669
TI  - Gene Time E{chi}pression Warper: a tool for alignment, template matching and
      visualization of gene expression time series.
AB  - An application tool for alignment, template matching and visualization of gene
      expression time series is presented. The core algorithm is based on dynamic time
      warping techniques used in the speech recognition field. These techniques allow
      for non-linear (elastic) alignment of temporal sequences of feature vectors and
      consequently enable detection of similar shapes with different phases.
      AVAILABILITY: The Java program, examples and a tutorial are available at
      http://www.psb.ugent.be/cbd/papers/gentxwarper/

PMID- 16293670
TI  - Enhanced recognition of protein transmembrane domains with prediction-based
      structural profiles.
AB  - MOTIVATION: Membrane domain prediction has recently been re-evaluated by several
      groups, suggesting that the accuracy of existing methods is still rather limited.
      In this work, we revisit this problem and propose novel methods for prediction of
      alpha-helical as well as beta-sheet transmembrane (TM) domains. The new approach
      is based on a compact representation of an amino acid residue and its
      environment, which consists of predicted solvent accessibility and secondary
      structure of each amino acid. A recently introduced method for solvent
      accessibility prediction trained on a set of soluble proteins is used here to
      indicate segments of residues that are predicted not to be accessible to water
      and, therefore, may be 'buried' in the membrane. While evolutionary profiles in
      the form of a multiple alignment are used to derive these simple 'structural
      profiles', they are not used explicitly for the membrane domain prediction and
      the overall number of parameters in the model is significantly reduced. This
      offers the possibility of a more reliable estimation of the free parameters in
      the model with a limited number of experimentally resolved membrane protein
      structures. RESULTS: Using cross-validated training on available sets of
      structurally resolved and non-redundant alpha and beta membrane proteins, we
      demonstrate that membrane domain prediction methods based on such a compact
      representation outperform approaches that utilize explicitly evolutionary
      profiles and multiple alignments. Moreover, using an external evaluation by the
      TMH Benchmark server we show that our final prediction protocol for the TM helix
      prediction is competitive with the state-of-the-art methods, achieving per
      residue accuracy of approximately 89% and per-segment accuracy of approximately
      80% on the set of high resolution structures used by the TMH Benchmark server. At
      the same time the observed rates of confusion with signal peptides and globular
      proteins are the lowest among the tested methods. The new method is available
      online at http://minnou.cchmc.org.

PMID- 16293672
TI  - Fibromyalgia and Gaucher's disease.
AB  - BACKGROUND: Patients with symptomatic Gaucher's disease sometimes have non
      specific symptoms (such as general malaise with widespread musculoskeletal pains)
      that respond poorly to enzyme replacement treatment. These may indicate
      fibromyalgia syndrome; if so, other therapeutic options might be more
      appropriate. AIM: To identify patients with Gaucher's disease for whom
      fibromyalgia-specific therapy may be therapeutic. DESIGN: Questionnaire-based
      survey. METHODS: Adult patients (n = 109) with non-neuronopathic Gaucher's
      disease and adult healthy controls (n = 108) completed health-related
      questionnaires including the Fibromyalgia Impact Questionnaire, and underwent
      testing with a dolorimeter to ascertain sensitivity at 22 tender points. RESULTS:
      Six patients, but no controls, met the criteria for fibromyalgia. Patients with
      fibromyalgia had a significantly greater incidence of co-morbidities (p = 0.014)
      relative to other patients with Gaucher's disease; four suffered from bone
      involvement and were receiving enzyme therapy, but two were untreated.
      DISCUSSION: The presence of fibromyalgia-specific trigger points may result from
      multiple aetiologies, or may be an independently-sorting predisposition. Our
      findings cannot distinguish between these possibilities, but if fibromyalgia were
      the cause, enzyme replacement therapy would be expensive and inappropriate.

PMID- 16293673
TI  - Post-partum intention to resume smoking.
AB  - Little is known about the motivational background of smoking after a period of
      nicotine abstinence during pregnancy. The study examines the intention to resume
      smoking (IRS) in the post-partum period and its predictive value for smoking
      within 12 months post-partum. In a sample of 301 women recruited from obstetric
      wards who reported having stopped smoking during pregnancy, data on IRS,
      sociodemographic variables, recent smoking behaviour and smoking in the social
      network were collected. Smoking status was assessed 6 and 12 months after
      pregnancy. Among all formerly smoking women, 39 (13%) intended to resume smoking
      and 262 (87%) intended to maintain abstinence. Women with IRS returned to smoking
      more often than women without IRS [77 versus 45%, odds ratio (OR) = 4.1, 95%
      confidence interval (CI): 1.89-9.05]. In a logistic regression model, IRS (OR =
      3.7, 95% CI: 1.51-9.01) and number of months currently abstinent (OR = 0.9, 95%
      CI: 0.76-0.96) attained statistical significance. IRS proved to be the main
      predictor for relapse; yet, women with no IRS are at risk to restart smoking
      again, too. IRS offers a cue for tailoring interventions.

PMID- 16293671
TI  - Molecular complementation of IL-12Rbeta1 deficiency reveals functional
      differences between IL-12Rbeta1 alleles including partial IL-12Rbeta1 deficiency.
AB  - Patients with mutations in IL12RB1, the gene encoding IL-12Rbeta1, suffer from
      combined IL-12R/IL-23R deficiency and are unusually susceptible to nontuberculous
      mycobacteria and salmonellae. The functional effects of amino acid changes in IL
      12Rbeta1, however, have not been determined at the molecular level. Molecular
      complementation studies are essential to demonstrate how structural amino acid
      changes affect IL-12Rbeta1 function, and whether functionally different IL
      12Rbeta1 alleles can be distinguished. Thirteen different IL-12Rbeta1 alleles,
      including 11 amino acid substitutions and the two major haplotypes (214Q-365M
      378G and 214R-365T-378R), were retrovirally transduced in IL-12Rbeta1 deficient
      human T cells. We provide functional evidence that L77P, R173P, C186S, R213W and
      Y367C are deleterious mutations leading to non-functional proteins. Conversely,
      S74R, R156H, H438Y, A525T and G594E are fully functional IL-12Rbeta1 variants.
      The C198R mutation leads to a partially functional IL-12Rbeta1, representing the
      first molecularly proven partial IL-12Rbeta1 deficiency. Interleukin-12 (IL-12)
      induced not only Interferon-gamma but also IL-10 in all responder but not in null
      mutant alleles, with intermediate levels in C198R. The QMG allele was found to be
      a higher IL-12 responder allele compared with the RTR allele. These results have
      implications for understanding IL-12R/IL-23R structure-function and the role of
      IL-12R/IL-23R in human disease.

PMID- 16293674
TI  - Breast cancer vaccines: a clinical reality or fairy tale?
AB  - The characterization of tumor antigens recognized by immune effector cells has
      opened the perspective of developing therapeutic vaccines in the field of breast
      cancer. The potential advantages of the vaccines are: (i) the induction of a
      robust immune response against tumors that are spontaneously weekly immunogenic;
      (ii) the tumor specificity for some antigens; (iii) the good tolerance and safety
      profile and (iv) the long-term immune memory, critical to prevent efficiently
      tumor recurrence. Most trials evaluating breast cancer vaccines have been carried
      out in patients with extended metastatic breast cancer, characterized by
      aggressive tumors, resistant to standard cytotoxic treatments, so that clinical
      efficacy was difficult to achieve. However, some significant immune responses
      against tumor antigens induced upon vaccinations were recorded. The aim of this
      review is to analyze the activity of vaccination strategies in current clinical
      trials. Data of clinical activity have been observed by using vaccines targeting
      HER2/neu protein, human telomerase reverse transcriptase, carcinoembryonic
      antigen and carbohydrate antigen given after stem cell rescue. The review
      discusses possible future directions for vaccine development and applications in
      the adjuvant setting.

PMID- 16293675
TI  - Secondary acute promyelocytic leukemia following irinotecan and oxaliplatin for
      advanced colon cancer.

PMID- 16293677
TI  - Treating HCV with ribavirin analogues and ribavirin-like molecules.
AB  - Nucleos(t)ide analogues have proven useful in the treatment of viral infections.
      Ribavirin is a nucleoside, guanosine analogue, whose mechanisms of action include
      inhibition of inosine monophosphate dehydrogenase (IMPDH), which is the key step
      in de novo guanine synthesis, a requirement for viral replication. In combination
      with pegylated interferon alfa, ribavirin is the standard of care for the
      treatment of chronic hepatitis C today. However, the medication is associated
      with significant haemolytic anaemia, which may require dose reduction,
      discontinuation or treatment with recombinant human erythropoietin. Dose
      reduction also appears to decrease sustained viral clearance rates. Newer IMPDH
      inhibitors are in various stages of development. Viramidine, a liver-targeting
      prodrug of ribavirin, has demonstrated significant antiviral activity and
      erythrocyte-sparing properties. It is currently in Phase 3 trials. Clinical
      trials of merimepodib, another investigational IMPDH inhibitor, have completed
      enrolment for a Phase 2b study as a third medication for administration with
      pegylated interferon plus ribavirin. Although other IMDPH inhibitors also have
      antiviral activity, these medications appear best suited as immunosuppressive
      medications at this time.

PMID- 16293676
TI  - Randomized phase III trials of adjuvant FAMTX or FEMTX compared with surgery
      alone in resected gastric cancer. A combined analysis of the EORTC GI Group and
      the ICCG.
AB  - BACKGROUND: In patients who underwent radical resection for gastric cancer, we
      investigate the relative efficacy of combined 5-fluorouracil+adriamycin or
      epirubicin and methotrexate with leucovorin rescue (FAMTX or FEMTX) compared with
      a control arm. PATIENTS AND METHODS: This report is a prospective combined
      analysis of two randomized clinical trials conducted on patients who underwent
      radical resection for histologically proven adenocarcinoma of the stomach or
      esophago-gastric junction. Three hundred and ninety-seven untreated patients, 206
      from 23 European Organization for Research and Treatment of Cancer (EORTC)
      institutions and 191 from 16 International Collaborative Cancer Group (ICCG)
      institutions, were randomized. Overall survival (OS) and disease-free survival
      (DFS) were estimated using the Kaplan-Meier method and the treatments were
      compared for these end-points by means of the log-rank test, retrospectively
      stratified by trial. RESULTS: In a planned combined analysis of the two trials,
      no significant differences were found between the treatment and control arms for
      either DFS (hazards ratio: 0.98, P=0.87) or OS (hazards ratio: 0.98, P=0.86). The
      5-year OS was 43% in the treatment arm and 44% in the control arm and the 5-year
      DFS was 41% and 42%, respectively. CONCLUSION: Neither FAMTX nor FEMTX can be
      advocated as adjuvant treatment in patients who undergo resection for gastric
      cancer.

PMID- 16293678
TI  - Guidelines for the laboratory diagnosis and susceptibility testing of methicillin
      resistant Staphylococcus aureus (MRSA).
AB  - These evidence-based guidelines have been produced after a literature review of
      the laboratory diagnosis and susceptibility testing of methicillin-resistant
      Staphylococcus aureus (MRSA). We have considered the detection of MRSA in
      screening samples and the detection of reduced susceptibility to glycopeptides in
      S. aureus. Recommendations are given for the identification of S. aureus and for
      suitable methods of susceptibility testing and screening for MRSA and for S.
      aureus with reduced susceptibility to glycopeptides. These guidelines indicate
      what tests should be used but not when the tests are applicable, as aspects of
      this are dealt with in guidelines on control of MRSA. There are currently several
      developments in screening media and molecular methods. It is likely that some of
      our recommendations will require modification as the new methods become
      available.

PMID- 16293679
TI  - IL-1beta directly excites isolated rat supraoptic neurons via upregulation of the
      osmosensory cation current.
AB  - Previous studies have shown that IL-1beta can excite the magnocellular
      neurosecretory cells (MNCs) of the hypothalamus. However, it is not known whether
      IL-1beta can have direct IL-1 receptor type 1 (IL-1R1)-mediated effects on MNCs,
      and little is known about the cellular mechanisms by which IL-1beta influences
      electrical activity in these cells. Here, we used patch-clamp recordings to
      examine the effects of IL-1beta on acutely isolated rat MNCs. We found that IL
      1beta directly excites MNCs in a dose-dependent manner and that this response can
      be blocked by an inhibitor of the IL-1R1. Voltage-clamp analysis of the current
      evoked by IL-1beta revealed a linear current-voltage relationship between -90 and
      -20 mV, and a reversal potential near -35 mV. This value was not affected by
      reducing the concentration of chloride ions in the external solution, indicating
      the involvement of a nonselective cation conductance. The effects of IL-1beta
      were inhibited by Na-salicylate, an inhibitor of cyclooxygenase. Moreover, the
      effects of IL-1beta were mimicked and occluded by PGE2, and were inhibited by AH
      23848, an antagonist of the PGE2 type 4 (i.e., EP4) receptor. The current evoked
      by IL-1beta was also abolished by 100 microM gadolinium (Gd3+), but was
      significantly larger when examined in cells preshrunk by negative pressure
      applied via the recording pipette. IL-1beta alone did not cause changes in cell
      volume nor in the mechanosensitivity of MNCs. We conclude that IL-1beta directly
      excites MNCs via an IL-1R1-mediated induction of PGE2 synthesis and EP4 receptor
      dependent autocrine upregulation of the nonselective cation conductance that
      underlies osmoreception.

PMID- 16293680
TI  - Pyrogenicity of CpG-DNA in mice: role of interleukin-6, cyclooxygenases, and
      nuclear factor-kappaB.
AB  - Bacterial DNA containing unmethylated cytosine-phosphate-guanosine motif (CpG
      DNA) has been identified as a pathogen-associated molecular pattern, which is
      recognized by Toll-like receptors and activates immune cells to produce
      cytokines. The aim of the study was to characterize the ability of CpG-DNA to
      induce fever in mice. Intravenous administration of unmethylated CpG-DNA 1826
      triggered an elevation of body temperature (T(b)) lasting several hours. The
      magnitude of T(b) elevation increased with an increase of dose of the
      oligonucleotide (administered in a range from 0.01 mg/kg to 1.0 mg/kg). A fever
      like increase of T(b) in mice was partially dependent on IL-6, as IL-6 deficient
      mice responded with reduced fever to the CpG-DNA 1826. Meloxicam and sulindac
      sulfide, inhibitors of cyclooxygenases, reduced fever in mice challenged with CpG
      DNA 1826, indicating that the process may also depend on prostaglandins. In fact,
      plasma levels of prostaglandin E(2), as well as IL-6, increased at 4 h
      postinjection of CpG-DNA 1826 into mice. These data demonstrate that the
      pathophysiological mechanism of the increase of T(b) induced by CpG-DNA 1826 is
      similar to fever induced by LPS. Both LPS and CpG-DNA 1826 failed to produce
      elevation of T(b) in mice deficient for a nuclear factor-kappaB (NF-kappaB) gene,
      further supporting the hypothesis that the two pyrogens provoke fever, using the
      same components of the cellular signaling metabolism. However, parthenolide, an
      inhibitor of I-kappaB kinase reduced fever due to CpG-DNA 1826, and did not
      affect fever to LPS, suggesting that the two structurally dissimilar pyrogens may
      affect different intracellular pathways leading to the upregulation of NF-kappaB.
      In support of this hypothesis, we demonstrate that C3H/HeJ mice, known to exhibit
      a mutation in the Toll-like receptor-4 gene, do not respond with fever to LPS.
      They respond, however, with fever after injection of CpG-DNA 1826. We conclude
      that bacterial DNA shares with components of the bacterial wall the capacity to
      elicit fever and may, consequently, be part of a novel class of exogenous
      pyrogens.

PMID- 16293681
TI  - Tubuloglomerular feedback-dependent modulation of renal myogenic autoregulation
      by nitric oxide.
AB  - Nonselective inhibition of nitric oxide (NO) synthase (NOS) augments myogenic
      autoregulation, an action that implies enhancement of pressure-induced
      constriction and dilatation. This pattern is not explained solely by interaction
      with a vasoconstrictor pathway. To test involvement of the Rho-Rho kinase pathway
      in modulation of autoregulation by NO, the selective Rho kinase inhibitor Y-27632
      and/or the NOS inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME) were
      infused into the left renal artery of anesthetized rats. Y-27632 and l-NAME were
      also infused into isolated, perfused hydronephrotic kidneys to assess myogenic
      autoregulation over a wide range of perfusion pressure. In vivo, l-NAME reduced
      renal vascular conductance and augmented myogenic autoregulation, as shown by
      increased slope of gain reduction and associated phase peak in the pressure-flow
      transfer function. Y-27632 (10 mumol/l) strongly dilated the renal vasculature
      and profoundly inhibited autoregulation in the absence or presence of l-NAME in
      vivo and in vitro. Afferent arteriolar constriction induced by 30 mmol/l KCl was
      reversed (-92 +/- 3%) by Y-27632. Phenylephrine caused strong renal
      vasoconstriction but did not affect autoregulation. Inhibition of neuronal NOS by
      N(5)-(1-imino-3-butenyl)-l-ornithine (l-VNIO) did not cause significant
      vasoconstriction but did augment myogenic autoregulation. Thus vasoconstriction
      is neither necessary (l-VNIO) nor sufficient (phenylephrine) to explain the
      augmented myogenic autoregulation induced by l-NAME. The effect of l-VNIO
      implicates tubuloglomerular feedback (TGF) and neuronal NOS at the macula densa
      in regulation of the myogenic mechanism. This conclusion was confirmed by the
      demonstration that systemic furosemide removed the TGF signature from the
      pressure-flow transfer function and significantly inhibited myogenic
      autoregulation. In the presence of furosemide, augmentation of myogenic
      autoregulation by l-NAME was significantly reduced. These results provide a
      potential mechanism to explain interaction between myogenic and TGF-mediated
      autoregulation.

PMID- 16293683
TI  - Upregulation of apical NHE3 in renal OK cells overexpressing the rodent alpha(1)
      subunit of the Na(+) pump.
AB  - Vectorial Na(+) reabsorption across the proximal tubule is mediated by apical
      entry of Na(+), primarily via Na(+)/H(+) exchanger isoform 3 (NHE3), and
      basolateral extrusion via the Na(+) pump (Na(+)-K(+)-ATPase). We hypothesized
      that regulation of Na(+) reabsorption should involve not only the activity of the
      basolateral Na(+)-K(+)-ATPase, but also the apical NHE3, in a concerted manner.
      To generate a cell line that overexpresses Na(+)-K(+)-ATPase, opossum kidney (OK)
      cells were transfected with the rodent Na(+)-K(+)-ATPase alpha(1)-subunit (pCMV
      ouabain vector), and native cells were used as a control. The existence of
      distinct functional classes of Na(+)-K(+)-ATPase in wild-type and transfected
      cells was confirmed by the inhibition profile of Na(+)-K(+)-ATPase activity by
      ouabain. In contrast to wild-type cells, transfected cells exhibited two IC(50)
      values for ouabain: the first value was similar to the IC(50) of control cells,
      and the second value was 2 log units greater than the first, consistent with the
      presence of rat and opossum alpha(1)-isozymes. It is shown that transfection of
      OK cells with Na(+)-K(+)-ATPase increased Na(+)-K(+)-ATPase and NHE3 activities.
      This was associated with overexpression of the Na(+)-K(+)-ATPase alpha(1)-subunit
      and NHE3 in transfected OK cells. The abundance of the Na(+)-K(+)-ATPase beta(1)
      subunit was slightly lower in transfected OK cells. In conclusion, the increase
      in expression and function of Na(+)-K(+)-ATPase in cells transfected with the
      rodent Na(+) pump alpha(1)-subunit cDNA is expected to stimulate apical Na(+)
      influx into the cells, thereby accounting for the observed stimulation of the
      apical NHE3 activity.

PMID- 16293684
TI  - Na-K-ATPase in rat cerebellar granule cells is redox sensitive.
AB  - Redox-induced regulation of the Na-K-ATPase was studied in dispersed rat
      cerebellar granule cells. Intracellular thiol redox state was modulated using
      glutathione (GSH)-conjugating agents and membrane-permeable ethyl ester of GSH
      (et-GSH) and Na-K-ATPase transport and hydrolytic activity monitored as a
      function of intracellular reduced thiol concentration. Depletion of cytosolic and
      mitochondrial GSH pools caused an increase in free radical production in
      mitochondria and rapid ATP deprivation with a subsequent decrease in transport
      but not hydrolytic activity of the Na-K-ATPase. Selective conjugation of
      cytosolic GSH did not affect free radical production and Na-K-ATPase function.
      Unexpectedly, overloading of cerebellar granule cells with GSH triggered global
      free radical burst originating most probably from GSH autooxidation. The latter
      was not followed by ATP depletion but resulted in suppression of active K(+)
      influx and a modest increase in mortality. Suppression of transport activity of
      the Na-K-ATPase was observed in granule cells exposed to both permeable et-GSH
      and impermeable GSH, with inhibitory effects of external and cytosolic GSH being
      additive. The obtained data indicate that redox state is a potent regulator of
      the Na-K-ATPase function. Shifts from an "optimal redox potential range" to
      higher or lower levels cause suppression of the Na-K pump activity.

PMID- 16293682
TI  - Altered sleep regulation in leptin-deficient mice.
AB  - Recent epidemiological, clinical, and experimental studies have demonstrated
      important links between sleep duration and architecture, circadian rhythms, and
      metabolism, although the genetic pathways that interconnect these processes are
      not well understood. Leptin is a circulating hormone and major adiposity signal
      involved in long-term energy homeostasis. In this study, we tested the hypothesis
      that leptin deficiency leads to impairments in sleep-wake regulation. Male ob/ob
      mice, a genetic model of leptin deficiency, had significantly disrupted sleep
      architecture with an elevated number of arousals from sleep [wild-type (WT) mice,
      108.2 +/- 7.2 vs. ob/ob mice, 148.4 +/- 4.5, P < 0.001] and increased stage
      shifts (WT, 519.1 +/- 25.2 vs. ob/ob, 748.0 +/- 38.8, P < 0.001) compared with WT
      mice. Ob/ob mice also had more frequent, but shorter-lasting sleep bouts compared
      with WT mice, indicating impaired sleep consolidation. Interestingly, ob/ob mice
      showed changes in sleep time, with increased amounts of 24-h non-rapid eye
      movement (NREM) sleep (WT, 601.5 +/- 10.8 vs. ob/ob, 669.2 +/- 13.4 min, P <
      0.001). Ob/ob mice had overall lower body temperature (WT, 35.1 +/- 0.2 vs.
      ob/ob, 33.4 +/- 0.2 degrees C, P < 0.001) and locomotor activity counts (WT,
      25125 +/- 2137 vs. ob/ob, 5219 +/- 1759, P < 0.001). Ob/ob mice displayed an
      attenuated diurnal rhythm of sleep-wake stages, NREM delta power, and locomotor
      activity. Following sleep deprivation, ob/ob mice had smaller amounts of NREM and
      REM recovery sleep, both in terms of the magnitude and the duration of the
      recovery response. In combination, these results indicate that leptin deficiency
      disrupts the regulation of sleep architecture and diurnal rhythmicity.

PMID- 16293685
TI  - Glyphosate inhibits rust diseases in glyphosate-resistant wheat and soybean.
AB  - Glyphosate is a broad-spectrum herbicide used for the control of weeds in
      glyphosate-resistant crops. Glyphosate inhibits 5-enolpyruvyl shikimate 3
      phosphate synthase, a key enzyme in the synthesis of aromatic amino acids in
      plants, fungi, and bacteria. Studies with glyphosate-resistant wheat have shown
      that glyphosate provided both preventive and curative activities against Puccinia
      striiformis f. sp. tritici and Puccinia triticina, which cause stripe and leaf
      rusts, respectively, in wheat. Growth-chamber studies demonstrated wheat rust
      control at multiple plant growth stages with a glyphosate spray dose typically
      recommended for weed control. Rust control was absent in formulation controls
      without glyphosate, dependent on systemic glyphosate concentrations in leaf
      tissues, and not mediated through induction of four common systemic acquired
      resistance genes. A field test with endemic stripe rust inoculum confirmed the
      activities of glyphosate pre- and postinfestation. Preliminary greenhouse studies
      also demonstrated that application of glyphosate in glyphosate-resistant soybeans
      suppressed Asian soybean rust, caused by Phakopsora pachyrhizi.

PMID- 16293686
TI  - Climatic unpredictability and parasitism of caterpillars: implications of global
      warming.
AB  - Insect outbreaks are expected to increase in frequency and intensity with
      projected changes in global climate through direct effects of climate change on
      insect populations and through disruption of community interactions. Although
      there is much concern about mean changes in global climate, the impact of
      climatic variability itself on species interactions has been little explored.
      Here, we compare caterpillar-parasitoid interactions across a broad gradient of
      climatic variability and find that the combined data in 15 geographically
      dispersed databases show a decrease in levels of parasitism as climatic
      variability increases. The dominant contribution to this pattern by relatively
      specialized parasitoid wasps suggests that climatic variability impairs the
      ability of parasitoids to track host populations. Given the important role of
      parasitoids in regulating insect herbivore populations in natural and managed
      systems, we predict an increase in the frequency and intensity of herbivore
      outbreaks through a disruption of enemy-herbivore dynamics as climates become
      more variable.

PMID- 16293687
TI  - Quantitative mass spectral evidence for the absence of circulating brain
      natriuretic peptide (BNP-32) in severe human heart failure.
AB  - C-terminal brain (B-type) natriuretic peptide (BNP)-32 is a widely used clinical
      biomarker for the diagnosis, prognosis, and treatment of heart failure (HF). The
      32-aa peptide is synthesized primarily in the atrial and ventricular myocardium
      and constitutes the mature biologically active form of immature BNP (pro-BNP).
      There has been mounting evidence that suggests BNP circulates in different
      structural forms that impact HF diagnosis and in vivo activity. Herein, we have
      developed and used an immunoaffinity purification assay to isolate endogenous BNP
      32 from New York Heart Association class IV patient plasma for subsequent
      analysis by nano-liquid chromatography (LC) electrospray ionization Fourier
      transform ion cyclotron resonance (FT-ICR) MS. We have introduced stable isotope
      labeled BNP-32 to the assayed plasma to enable quantification of endogenous
      levels of BNP-32. Unlike the chemically nonspecific point-of-care tests (POCTs)
      and RIAs used worldwide to quantify BNP-32 from plasma, FT-ICR-MS (unprecedented
      mass measurement accuracy) coupled with LC (retention time) affords extraordinary
      molecular specificity, and when combined with the use of internal standards is
      able to confidently identify and quantify BNP-32. The significance of this work
      is despite exceedingly high circulating levels of BNP-32 in the New York Heart
      Association class IV patients as determined by POCTs (>290 fmol/ml) nano-LC
      electrospray ionization-FT-ICR-MS data did not reveal any endogenous BNP-32.
      These results provide molecularly specific evidence for the absence of
      circulating BNP-32 in advanced-stage HF patients and suggest the existence of
      altered forms of BNP that are contributing to the POCT values.

PMID- 16293688
TI  - Self renewal, expansion, and transfection of rat spermatogonial stem cells in
      culture.
AB  - The use of a transgenic line of rats that express enhanced GFP (EGFP) exclusively
      in the germ line has allowed a separation of feeder layers and contaminating
      testis somatic cells from germ cells and the identification of a set of
      spermatogonial stem cell marker transcripts. With these molecular markers as a
      guide, we have now devised culture conditions where rat spermatogonial stem cells
      renew and proliferate in culture with a doubling time between 3 and 4 days. The
      marker transcripts increase in relative abundance as a function of time in
      culture, and the stem cells retain competency to colonize and develop into
      spermatids after transplantation to the testes of recipient rats. The cells also
      remain euploid after at least 12 passages. Cell lines could be isolated and
      cryopreserved and, upon subsequent thawing, continue to self renew. Transfection
      of the spermatogonial stem cells with a plasmid containing the neomycin
      phosphotransferase (neo) selectable marker resulted in selection of G418
      resistant cell lines that effectively colonize recipient testes, suggesting that
      gene targeting is now feasible in the rat.

PMID- 16293691
TI  - Burning down the brewery: establishing and evacuating an ancient imperial colony
      at Cerro Baul, Peru.
AB  - Before the Inca reigned, two empires held sway over the central Andes from anno
      Domini 600 to 1000: the Wari empire to the north ruled much of Peru, and Tiwanaku
      to the south reigned in Bolivia. Face-to-face contact came when both colonized
      the Moquegua Valley sierra in southern Peru. The state-sponsored Wari incursion,
      described here, entailed large-scale agrarian reclamation to sustain the
      occupation of two hills and the adjacent high mesa of Cerro Baul. Monumental
      buildings were erected atop the mesa to serve an embassy-like delegation of
      nobles and attendant personnel that endured for centuries. Final evacuation of
      the Baul enclave was accompanied by elaborate ceremonies with brewing, drinking,
      feasting, vessel smashing, and building burning.

PMID- 16293689
TI  - Streptococcal viability and diminished stress tolerance in mutants lacking the
      signal recognition particle pathway or YidC2.
AB  - The signal recognition particle (SRP)-translocation pathway is conserved in all
      three domains of life and delivers membrane and secretory proteins to the
      cytoplasmic membrane or endoplasmic reticulum. We determined the requirement in
      the cariogenic oral pathogen Streptocococcus mutans of the three universally
      conserved elements of the SRP pathway: Ffh/SRP54, scRNA, and FtsY/SRalpha.
      Previously, we reported that insertional interruption of S. mutans ffh was not
      lethal, but resulted in acid sensitivity. To test whether S. mutans could survive
      extensive disruption of the SRP pathway, single and double deletions of genes
      encoding Ffh, scRNA, and FtsY were generated. Without environmental stressors,
      all mutant strains were viable, but unlike the wild-type, none could initiate
      growth at pH 5.0 or in 3.5% NaCl. Survival of challenge with 0.3 mM H(2)O(2) was
      also diminished without ffh. Members of the YidC/Oxa1/Alb3 family are also
      ubiquitous, involved in the translocation and assembly of membrane proteins, and
      have been identified in prokaryotes/mitochondria/chloroplasts. Two genes encoding
      YidC homologs, YidC1 and YidC2, are present in streptococcal genomes with both
      expressed in S. mutans. Deletion of YidC1 demonstrated no obvious phenotype.
      Elimination of YidC2 resulted in a stress-sensitive phenotype similar to SRP
      pathway mutants. Mutants lacking both YidC2 and SRP components were severely
      impaired and barely able to grow, even in the absence of environmental stress.
      Here, we report the dispensability of the cotranslational SRP protein
      translocation system in a bacterium. In S. mutans, this pathway contributes to
      protection against rapid environmental challenge and may overlap functionally
      with YidC2.

PMID- 16293690
TI  - Visualization of a primary anti-tumor immune response by positron emission
      tomography.
AB  - Current methodologies that monitor immune responses rely on invasive techniques
      that sample tissues at a given point in time. New technologies are needed to
      elucidate the temporal patterns of immune responses and the spatial distribution
      of immune cells on a whole-body scale. We describe a noninvasive, quantitative,
      and tomographic approach to visualize a primary anti-tumor immune response by
      using positron emission tomography (PET). Bone marrow chimeric mice were
      generated by engraftment of hematopoietic stem and progenitor cells transduced
      with a trifusion reporter gene encoding synthetic Renilla luciferase (hRluc),
      EGFP, and Herpes virus thymidine kinase (sr39TK). Mice were challenged with the
      Moloney murine sarcoma and leukemia virus complex (M-MSV/M-MuLV), and the induced
      immune response was monitored by using PET. Hematopoietic cells were visualized
      by using 9-[4-[(18)F]fluoro-3-(hydroxymethyl)butyl]guanine ([(18)F]FHBG), a
      radioactive substrate specific for the sr39TK PET reporter protein. Immune cell
      localization and expansion were seen at the tumor and draining lymph nodes
      (DLNs). 2-[(18)F]fluoro-2-deoxy-D-glucose ([(18)F]FDG), which is sequestered in
      metabolically active cells, was used to follow tumor growth and regression.
      Elevated glucose metabolism was also seen in activated lymphocytes in the DLNs by
      using the [(18)F]FDG probe. When M-MSV/M-MuLV-challenged mice were treated with
      the immunosuppressive drug dexamethasone, activation and expansion of immune cell
      populations in the DLNs could no longer be detected with PET imaging. The method
      we describe can be used to kinetically measure the induction and therapeutic
      modulations of cell-mediated immune responses.

PMID- 16293692
TI  - Coevolution of generalist feeding ecologies and gyrencephalic mushroom bodies in
      insects.
AB  - Here we demonstrate the independent acquisition of strikingly similar brain
      architectures across divergent insect taxa and even across phyla under similar
      adaptive pressures. Convoluted cortical gyri-like structures characterize the
      mushroom body calyces in the brains of certain species of insects; we have
      investigated in detail the cellular and ecological correlates of this morphology
      in the Scarabaeidae (scarab beetles). "Gyrencephalic" mushroom bodies with
      increased surface area and volume of calycal synaptic neuropils and increased
      intrinsic neuron number characterize only those species belonging to generalist
      plant-feeding subfamilies, whereas significantly smaller "lissencephalic"
      mushroom bodies are found in more specialist dung-feeding scarab beetles. Such
      changes are not unique to scarabs or herbivores, because the mushroom bodies of
      predatory beetles display similar morphological disparities in generalists vs.
      specialists. We also show that gyrencephalic mushroom bodies in generalist
      scarabs are not associated with an increase in the size of their primary input
      neuropil, the antennal lobe, or in the number of antennal lobe glomeruli but
      rather with an apparent increase in the density of calycal microglomeruli and the
      acquisition of calycal subpartitions. These differences suggest changes in calyx
      circuitry facilitating the increased demands on processing capability and
      flexibility imposed by the evolution of a generalist feeding ecology.

PMID- 16293693
TI  - MINISEED3 (MINI3), a WRKY family gene, and HAIKU2 (IKU2), a leucine-rich repeat
      (LRR) KINASE gene, are regulators of seed size in Arabidopsis.
AB  - We have identified mutant alleles of two sporophytically acting genes, HAIKU2
      (IKU2) and MINISEED3 (MINI3). Homozygotes of these alleles produce a small seed
      phenotype associated with reduced growth and early cellularization of the
      endosperm. This phenotype is similar to that described for another seed size
      gene, IKU1. MINI3 encodes WRKY10, a WRKY class transcription factor. MINI3
      promoter::GUS fusions show the gene is expressed in pollen and in the developing
      endosperm from the two nuclei stage at approximately 12 hr postfertilization to
      endosperm cellularization at approximately 96 hr. MINI3 is also expressed in the
      globular embryo but not in the late heart stage of embryo development. The early
      endosperm expression of MINI3 is independent of its parent of origin. IKU2
      encodes a leucine-rich repeat (LRR) KINASE (At3g19700). IKU2::GUS has a similar
      expression pattern to that of MINI3. The patterns of expression of the two genes
      and their similar phenotypes indicate they may operate in the same genetic
      pathway. Additionally, we found that both MINI3 and IKU2 showed decreased
      expression in the iku1-1 mutant. IKU2 expression was reduced in a mini3-1
      background, whereas MINI3 expression was unaltered in the iku2-3 mutant. These
      data suggest the successive action of the three genes IKU1, IKU2, and MINI3 in
      the same pathway of seed development.

PMID- 16293694
TI  - Albumin endocytosis in proximal tubule cells is modulated by angiotensin II
      through an AT2 receptor-mediated protein kinase B activation.
AB  - Albumin endocytosis in renal proximal tubule cells is a clathrin- and receptor
      mediated mechanism that, in several pathophysiological conditions, is involved in
      initiating or promoting tubule-interstitial disease. Although much work has been
      done on this pathway, the regulation of albumin endocytosis in proximal tubule
      cells is not well understood. Here, we study the modulation by angiotensin II
      (Ang II) of albumin endocytosis in LLC-PK1, a model of proximal tubule cells. We
      observed that Ang II increases albumin endocytosis by approximately 100% at 10(
      9) M. This effect is completely reversed by 10(-9) M PD123319, a specific AT(2)
      receptor antagonist, but not by losartan, a specific AT(1) receptor antagonist,
      at concentrations up to 10(-7) M. The Ang II effect on albumin endocytosis is
      also reversed by: phosphoinositide 3-kinase inhibitors LY294002 (2.5 x 10(-6) M)
      or wortmannin (10(-7) M), the protein kinase B inhibitor (2 x 10(-5) M), and
      staurosporine (2 x 10(-6) M), an inhibitor of 3'-phosphoinositide-dependent
      kinase 1. Ang II induced the selective phosphorylation of protein kinase B (PKB)
      at the Thr-308 residue without a change in Ser-473 phosphorylation, a combination
      that leads to an increase in PKB activity. These effects were completely
      abolished by 3 x 10(-6) M staurosporine or 10(-8) M PD123319. Our experiments
      also showed that PKB is present in the membrane fraction in overnight-starved LLC
      PK1 cells. Taken together, these data show that Ang II increases albumin
      endocytosis through an AT(2) receptor mediated by activation of PKB in the plasma
      membrane, which depends on the basal activity of the phosphatidyl-inositol 3
      kinase.

PMID- 16293695
TI  - An allosteric model for heterogeneous receptor complexes: understanding bacterial
      chemotaxis responses to multiple stimuli.
AB  - The classical Monod-Wyman-Changeux model for homogeneous allosteric protein
      complex is generalized in this article to model the responses of heterogeneous
      receptor complexes to multiple types of ligand stimulus. We show that the recent
      in vivo experimental data of Escherichia coli chemotaxis responses for mutant
      strains with different expression levels of the chemo-receptors to different
      types of stimulus [Sourjik, V. & Berg, H. C. (2004) Nature 428, 437-441] all can
      be explained consistently within this generalized Monod-Wyman-Changeux model.
      Based on the model and the existing data, responses of all of the strains
      (studied in this article) to the presence of any combinations of ligand (Ser and
      MeAsp) concentrations are predicted quantitatively for future experimental
      verification. Through modeling the in vivo response data, our study reveals
      important information about the properties of different types of individual
      receptors, as well as the composition of the cluster. The energetic contribution
      of the nonligand binding, cytoplasmic parts of the cluster, such as CheA and
      CheW, is also discussed. The generalized allosteric model provides a consistent
      framework in understanding signal integration and differentiation in bacterial
      chemotaxis. It should also be useful for studying the functions of other
      heterogeneous receptor complexes.

PMID- 16293696
TI  - 3D structure of Alzheimer's amyloid-beta(1-42) fibrils.
AB  - Alzheimer's disease is the most fatal neurodegenerative disorder wherein the
      process of amyloid-beta (Abeta) amyloidogenesis appears causative. Here, we
      present the 3D structure of the fibrils comprising Abeta(1-42), which was
      obtained by using hydrogen-bonding constraints from quenched hydrogen/deuterium
      exchange NMR, side-chain packing constraints from pairwise mutagenesis studies,
      and parallel, in-register beta-sheet arrangement from previous solid-state NMR
      studies. Although residues 1-17 are disordered, residues 18-42 form a beta-strand
      turn-beta-strand motif that contains two intermolecular, parallel, in-register
      beta-sheets that are formed by residues 18-26 (beta1) and 31-42 (beta2). At least
      two molecules of Abeta(1-42) are required to achieve the repeating structure of a
      protofilament. Intermolecular side-chain contacts are formed between the odd
      numbered residues of strand beta1 of the nth molecule and the even-numbered
      residues of strand beta2 of the (n - 1)th molecule. This interaction pattern
      leads to partially unpaired beta-strands at the fibrillar ends, which explains
      the sequence selectivity, the cooperativity, and the apparent unidirectionality
      of Abeta fibril growth. It also provides a structural basis for fibrillization
      inhibitors.

PMID- 16293697
TI  - Leukotriene B4 signaling through NF-kappaB-dependent BLT1 receptors on vascular
      smooth muscle cells in atherosclerosis and intimal hyperplasia.
AB  - Leukotriene B(4) (LTB(4)), a potent leukocyte chemoattractant derived from the 5
      lipoxygenase metabolism of arachidonic acid, exerts its action by means of
      specific cell surface receptors, denoted BLT(1) and BLT(2). In this study, BLT(1)
      receptor proteins were detected in human carotid artery atherosclerotic plaques,
      colocalizing with markers for macrophages, endothelial cells, and vascular smooth
      muscle cells (SMC). Challenge of human coronary artery SMC with either LTB(4) or
      U75302, a partial agonist that is selective for the BLT(1) receptor, induced an
      approximately 4-fold increase of whole-cell currents by using the patch-clamp
      technique, indicating that these cells express functional BLT(1) receptors.
      LTB(4) induced migration and proliferation of SMC in vitro, and treatment with
      the BLT receptor antagonist BIIL 284 (10 mg/kg, once daily) for 14 days after
      carotid artery balloon injury in vivo inhibited intimal hyperplasia in rats. In
      the latter model, SMC derived from the intima exhibited increased levels of
      BLT(1) receptor mRNA compared with medial SMC. BLT receptor up-regulation in the
      intima in vivo, as well as that induced by IL-1beta in vitro, were prevented by
      transfection with a dominant-negative form of Ikappa kinase beta carried by
      adenovirus, indicating that BLT(1) receptor expression depends on NF-kappaBeta.
      These results show that LTB(4) activates functional BLT(1) receptors on vascular
      SMC, inducing chemotaxis and proliferation, and that BLT(1) receptors were up
      regulated through an Ikappa kinase beta/NF-kappaB-dependent pathway. Inhibition
      of LTB(4)/BLT(1) signaling during the response to vascular injury reduced intimal
      hyperplasia, suggesting this pathway as a possible target for therapy.

PMID- 16293700
TI  - Improving access for the poorest to public sector health services: insights from
      Kirivong Operational Health District in Cambodia.
AB  - This article presents research findings into the effectiveness of an innovative
      equity fund approach to improving access to public sector health services for the
      poor in Kirivong Operational Health District in Cambodia. The operational health
      district is the lowest organizational level in the Cambodian health system,
      providing services through health centres and a single referral hospital. An
      equity fund involves a third party identifying the poor and paying user fees on
      their behalf by reimbursing the service provider, thus relieving health staff of
      such responsibility. We explore the appropriateness of utilizing community
      members to identify the poorest. The impact of newly introduced pagoda-managed
      equity funds on access to public health services for the poorest, and on their
      out-of-pocket expenditure during illness episodes, is then examined. We conclude
      with an evaluation of the contribution of the equity funds to community
      participation. The research indicates that identification by community members of
      those eligible for equity funds is feasible, accrues minimal direct costs, and is
      effective. Households identified as eligible for equity fund benefits were poorer
      than those identified as non-beneficiaries. Direct costs associated with seeking
      care were considerably lower for equity fund beneficiaries than for non
      beneficiaries, and fewer beneficiaries than non-beneficiaries initially consulted
      the private sector, providing evidence of the equity fund's ability to attract
      the poorest to the public sector. The level and nature of community participation
      was enhanced considerably following the introduction of the pagoda-managed equity
      funds. In order to maximize and sustain the equity benefits of such funds, we
      recommend that external agencies (such as international non-governmental
      organizations) limit their role to the provision of technical support and advice,
      rather than taking the lead on implementation and administration. Facilitating
      the design, implementation, administration and management of equity funds by
      indigenous community-based organizations has the advantage of not only greatly
      reducing administrative costs, allowing a large proportion of the fund to be
      spent on services for the poor, but also of enhancing local ownership, thus
      increasing the likelihood of equity funds being sustained in the future.

PMID- 16293698
TI  - Lrp5-independent activation of Wnt signaling by lithium chloride increases bone
      formation and bone mass in mice.
AB  - One of the well characterized cell biologic actions of lithium is the inhibition
      of glycogen synthase kinase-3beta and the consequent activation of canonical Wnt
      signaling. Because deficient Wnt signaling has been implicated in disorders of
      reduced bone mass, we tested whether lithium could improve bone mass in mice. We
      gavage-fed lithium chloride to 8-week-old mice from three different strains
      (Lrp5(-/-), SAMP6, and C57BL/6) and assessed the effect on bone metabolism after
      4 weeks of therapy. Lrp5(-/-) mice lack the Wnt coreceptor low-density
      lipoprotein receptor-related protein 5 and have markedly reduced bone mass.
      Lithium, which is predicted to act downstream of this receptor, restored bone
      metabolism and bone mass to near wild-type levels in these mice. SAMP6 mice have
      accelerated osteoporosis due to inadequate osteoblast renewal. Lithium
      significantly improved bone mass in these mice and in wild-type C57BL/6 mice. We
      found that lithium activated canonical Wnt signaling in cultured calvarial
      osteoblasts from Lrp5(-/-) mice ex vivo and that lithium-treated mice had
      increased expression of Wnt-responsive genes in their bone marrow cells in vivo.
      These data lead us to conclude that lithium enhances bone formation and improves
      bone mass in mice and that it may do so via activation of the canonical Wnt
      pathway. Lithium has been used safely and effectively for over half a century in
      the treatment of bipolar illness. Prospective studies in patients receiving
      lithium should determine whether it also improves bone mass in humans.

PMID- 16293701
TI  - Upregulation of vascular inducible nitric oxide synthase mediates the hypotensive
      effect of ethanol in conscious female rats.
AB  - Previous reports from our laboratory have shown that ethanol elicits hypotension
      in female but not in male rats and that this effect of ethanol is estrogen
      dependent (El-Mass MM and Abdel-Rahman AA. Alcohol Clin Exp Res 23: 624-632,
      1999; El-Mass MM and Abdel-Rahman AA. Clin Exp Hypertens 21: 1429-1445, 1999). In
      the present study, we tested the hypothesis that ethanol lowers blood pressure in
      female rats via upregulation of the inducible nitric oxide synthase (iNOS) in
      vascular tissues. The effects of pretreatment with NG-nitro-L-arginine (NOARG;
      nonselective nitric oxide synthase inhibitor) or aminoguanidine (selective iNOS
      inhibitor) on hemodynamic responses elicited by intragastric (ig) ethanol were
      determined in conscious female rats. Changes in vascular (aortic) iNOS protein
      expression evoked by ethanol in the presence and absence of aminoguanidine were
      also measured by immunohistochemistry. Compared with control (water treated)
      female rats, ethanol (1 g/kg ig) elicited hypotension that was associated with a
      significant increase in the aortic iNOS activity. The hypotensive effect of
      ethanol was virtually abolished in rats infused with the nitric oxide synthase
      inhibitor NOARG, suggesting a role for nitric oxide in ethanol hypotension. The
      inability of ethanol to lower blood pressure in NOARG-treated rats cannot be
      attributed to the presence of elevated blood pressure in these rats because
      ethanol produced hypotension when blood pressure was raised to comparable levels
      with phenylephrine infusion. Selective inhibition of iNOS by aminoguanidine (45
      mg/kg ip), which had no effect on baseline blood pressure, abolished both the
      hypotensive action of subsequently administered ethanol and the associated
      increases in aortic iNOS content. These findings implicate vascular iNOS, at
      least partly, in the acute hypotensive action of ethanol in female rats.

PMID- 16293699
TI  - Concentration dynamics of nitric oxide in rat hippocampal subregions evoked by
      stimulation of the NMDA glutamate receptor.
AB  - Nitric oxide (*NO) production in response to stimulation of the NMDA glutamate
      receptor is implicated not only in the synaptic plasticity in hippocampus but may
      also participate in excitotoxic cell death. Using *NO-selective microssensors
      inserted into the diffusional field of *NO in acute hippocampal slices, we
      describe the *NO concentration dynamics evoked by NMDA receptor activation and
      report profound differences along the trisynaptic loop of the hippocampus. We
      measured the oxygen gradient across the slice thickness and conclude that *NO
      measurements were performed at cell layers experiencing physiological oxygen
      tensions. Recordings performed at increasing distances from the point of NMDA
      receptor stimulation resulted in a progressive decrease of *NO signals, reaching
      undetectable levels for distances >400 microm, supporting the notion of a wide
      diffusional spread of endogenously generated *NO in the hippocampus. Neither a
      picoinjection nor a continuous perfusion of NMDA resulted in high steady-state
      *NO levels; rather all signals were transient, suggesting that cells are able to
      efficiently respond to high *NO concentrations (typically 200-400 nM) bringing it
      to very low nM levels; the claimed high micromolar *NO range achieved by
      excessive stimulation of NMDA receptor may have to be reevaluated. The distinct
      responses to NMDA receptor stimulation along the trysynaptic loop suggest a
      differential *NO activity and/or regulation among the hippocampal subregions.
      These findings may be relevant for the understanding of the role of *NO in
      physiologic mechanisms in the hippocampus and the differential sensitivity of the
      hippocampal subregions to NMDA receptor-dependent neurodegeneration.

PMID- 16293703
TI  - Slower skeletal muscle phenotypes are critical for constitutive expression of
      Hsp70 in overloaded rat plantaris muscle.
AB  - Heat shock protein 72 (Hsp70) is constitutively expressed in rat hindlimb
      muscles, reportedly in proportion to their content of type I myosin heavy chain.
      This distribution pattern has been suggested to result from the higher
      recruitment and activity of such muscles and/or a specific relationship between
      myosin phenotype and Hsp70 content. To differentiate between these possibilities,
      the fiber-specific distribution of Hsp70 was examined in male Sprague-Dawley rat
      plantaris under control conditions, following a fast-to-slow phenotypic shift in
      response to surgically induced overload (O) and in response to O when the
      phenotypic shift was prevented by 3,5,3'-triiodo-dl-thyronine administration.
      Constitutive expression of Hsp70 was restricted to type I and IIa fibers in
      plantaris from control rats, and this fiber-specific pattern of expression was
      maintained following O of up to 28 days, although Hsp70 content in the O muscle
      doubled. When O (for 40 days) of the plantaris was combined with 3,5,3'-triiodo
      dl-thyronine administration, despite typical hypertrophy in the overloaded
      plantaris, prevention of the normal phenotypic transformation also blocked the
      increased expression of Hsp70 observed in euthyroid controls. Collectively, these
      data suggest that chronic changes in constitutive expression of Hsp70 with
      altered contractile activity appear critically dependent on fast-to-slow
      phenotypic remodeling.

PMID- 16293702
TI  - Protocol for measurement of liver fat by computed tomography.
AB  - To develop a protocol for measurement of liver fat using computed tomography
      (CT), we conducted a preliminary study with 118 men and 76 women to determine a
      readily identifiable vertebral landmark at which the CT image displayed both
      liver and spleen. Analysis of five landmarks revealed that the CT image obtained
      at the T12-L1 level simultaneously displayed the liver and spleen in 90% of the
      men and women. The T12-L1 protocol was cross-validated on a sample of 130 men and
      113 women. In this sample, we also assessed the regional characteristics of liver
      and spleen tissue attenuation at the T12-L1 level by subdividing each image into
      quartiles from anterior to posterior, each of which were further divided into
      medial and lateral regions. A similar analysis was performed on images located 12
      mm above and below T12-L1. The T12-L1 image displayed both liver and spleen in
      92% (403 of 437) of the combined study sample. There was a significant (P<0.005)
      stepwise increase in attenuation values [Hounsfield units (HU)] from the inferior
      to superior image. Although some significant (P<0.05) differences were observed
      between the eight regions by comparison to the whole liver or spleen, the average
      magnitude of the difference was <2.0 HU for liver and <3.5 HU for spleen.
      Acquisition of a single CT image at the T12-L1 level is a practical and reliable
      method for routine measurement of liver fat in research and clinical settings.

PMID- 16293704
TI  - Near-infrared spectroscopy measurements of cerebral blood flow and oxygen
      consumption following hypoxia-ischemia in newborn piglets.
AB  - Impaired oxidative metabolism following hypoxia-ischemia (HI) is believed to be
      an early indicator of delayed brain injury. The cerebral metabolic rate of oxygen
      (CMRO2) can be measured by combining near-infrared spectroscopy (NIRS)
      measurements of cerebral blood flow (CBF) and cerebral deoxy-hemoglobin
      concentration. The ability of NIRS to measure changes in CMRO2 following HI was
      investigated in newborn piglets. Nine piglets were subjected to 30 min of HI by
      occluding both carotid arteries and reducing the fraction of inspired oxygen to
      8%. An additional nine piglets served as sham-operated controls. Measurements of
      CBF, oxygen extraction fraction (OEF), and CMRO2 were obtained at baseline and at
      6 h after the HI insult. Of the three parameters, only CMRO2 showed a persistent
      and significant change after HI. Five minutes after reoxygenation, there was a
      28+/-12% (mean+/-SE) decrease in CMRO2, a 72+/-50% increase in CBF, and a 56+/
      19% decrease in OEF compared with baseline (P<0.05). By 30 min postinsult and for
      the remainder of the study, there were no significant differences in CBF and OEF
      between control and insult groups, whereas CMRO2 remained depressed throughout
      the 6-h postinsult period. This study demonstrates that NIRS can measure
      decreases in CMRO2 caused by HI. The results highlight the potential for NIRS to
      be used in the neonatal intensive care unit to detect delayed brain damage.

PMID- 16293705
TI  - The effect of lung inflation on the inspiratory action of the canine parasternal
      intercostals.
AB  - Inflation induces a marked decrease in the lung-expanding ability of the
      diaphragm, but its effect on the parasternal intercostal muscles is uncertain. To
      assess this effect, the phrenic nerves and the external intercostals were severed
      in anesthetized, vagotomized dogs, such that the parasternal intercostals were
      the only muscles active during inspiration, and the endotracheal tube was
      occluded at different lung volumes. Although the inspiratory electromyographic
      activity recorded from the muscles was constant, the change in airway opening
      pressure decreased with inflation from -7.2+/-0.6 cmH2O at functional residual
      capacity to -2.2+/-0.2 cmH2O at 20-cmH2O transrespiratory pressure (P<0.001). The
      inspiratory cranial displacement of the ribs remained virtually unchanged, and
      the inspiratory caudal displacement of the sternum decreased moderately. However,
      the inspiratory outward rib displacement decreased markedly and continuously; at
      20 cmH2O, this displacement was only 23+/-2% of the value at functional residual
      capacity. Calculations based on this alteration yielded substantial decreases in
      the change in airway opening pressure. It is concluded that, in the dog, 1)
      inflation affects adversely the lung-expanding actions of both the parasternal
      intercostals and the diaphragm; and 2) the adverse effect of inflation on the
      parasternal intercostals is primarily related to the alteration in the kinematics
      of the ribs. As a corollary, it is likely that hyperinflation also has a negative
      impact on the parasternal intercostals in patients with chronic obstructive
      pulmonary disease.

PMID- 16293706
TI  - Reduced forearm alpha1-adrenergic vasoconstriction is associated with enhanced
      heart rate fluctuations in humans.
AB  - In the present study, we assessed whether heart rate (HR) or arterial pressure
      fluctuations are enhanced in healthy young humans with reduced alpha-adrenergic
      vasoconstrictor responses and, if so, whether this occurs for both alpha1- and
      alpha2-adrenergic receptor-mediated vasoconstriction. Arterial pressure (brachial
      artery catheter) and HR (ECG) were monitored continuously, and alpha1- and alpha2
      adrenergic responsiveness was determined by assessing the effects of brachial
      artery infusions of phenylephrine (alpha1-adrenergic agonist) and dexmedetomidine
      (alpha2-adrenergic agonist), respectively, on forearm blood flow (strain gauge
      plethysmography). alpha1-Adrenergic responsiveness varied markedly among the
      subjects (n=20) and was inversely correlated with coefficient of variation for HR
      (R2=0.37, P<0.01), whereas the responsiveness was not correlated with the
      coefficient of variation for either systolic or diastolic arterial pressure.
      alpha1-Adrenergic responsiveness was inversely and more strongly correlated with
      baroreflex sensitivity (R2=0.62, P<0.0001), determined from beat-to-beat changes
      in HR and systolic arterial pressure, than the coefficient of variation for HR.
      On the other hand, alpha2-adrenergic responsiveness was not correlated with any
      of the parameters determined above. These results suggest that, in healthy young
      subjects, the enhanced HR response to changes in systolic pressure helps maintain
      the stability of arterial blood pressure when alpha1-adrenergic responsiveness is
      reduced.

PMID- 16293707
TI  - Expression of toll-like receptors by human muscle cells in vitro and in vivo:
      TLR3 is highly expressed in inflammatory and HIV myopathies, mediates IL-8
      release and up-regulation of NKG2D-ligands.
AB  - The particular microenvironment of the skeletal muscle can be the site of complex
      immune reactions. Toll-like receptors (TLRs) mediate inflammatory stimuli from
      pathogens and endogenous danger signals and link the innate and adaptive immune
      system. We investigated innate immune responses in human muscle. Analyzing TLR1-9
      mRNA in cultured myoblasts and rhabdomyosarcoma cells, we found constitutive
      expression of TLR3. The TLR3 ligand Poly (I:C), a synthetic analog of dsRNA, and
      IFN-gamma increased TLR3 levels. TLR3 was mainly localized intracellularly and
      regulated at the protein level. Poly (I:C) challenge 1) activated nuclear factor
      kappaB (NF-kappaB), 2) increased IL-8 release, and 3) up-regulated NKG2D ligands
      and NK-cell-mediated lysis of muscle cells. We examined muscle biopsy specimens
      of 6 HIV patients with inclusion body myositis/polymyositis (IBM/PM), 7 cases of
      sporadic IBM and 9 nonmyopathic controls for TLR3 expression. TLR3 mRNA levels
      were elevated in biopsy specimens from patients with IBM and HIV-myopathies.
      Muscle fibers in inflammatory myopathies expressed TLR3 in close proximity of
      infiltrating mononuclear cells. Taken together, our study suggests an important
      role of TLR3 in the immunobiology of muscle, and has substantial implications for
      the understanding of the pathogenesis of inflammatory myopathies or therapeutic
      interventions like vaccinations or gene transfer.

PMID- 16293708
TI  - ERK1/2 is an endogenous negative regulator of the gamma-secretase activity.
AB  - As an essential protease in the generation of amyloid beta, gamma-secretase is
      believed to play an important role in the pathogenesis of Alzheimer's disease.
      Although a great deal of progress has been made in identifying the components of
      gamma-secretase complex, the endogenous regulatory mechanism of gamma-secretase
      is unknown. Here we show that gamma-secretase is endogenously regulated via
      extracellular signal regulated MAP kinase (ERK) 1/2-dependent mitogen-activated
      protein kinase (MAPK) pathway. The inhibition of ERK1/2 activity, either by a
      treatment with a MEK inhibitor or an ERK knockdown transfection, dramatically
      increased gamma-secretase activity in several different cell types. JNK or p38
      kinase inhibitors had little effect, indicating that the effect is specific to
      ERK1/2-dependent MAPK pathway. Conversely, increased ERK1/2 activity, by adding
      purified active ERK1/2 or EGF-induced activation of ERK1/2, significantly reduced
      gamma-secretase activity, demonstrating down-regulation of gamma-secretase
      activity by ERK1/2. Whereas gamma-secretase expression was not affected by
      ERK1/2, its activity was enhanced by phosphatase treatment, indicating that
      ERK1/2 regulates gamma-secretase activity by altering the pattern of
      phophorylation. Among the components of isolated gamma-secretase complex, only
      nicastrin was phosphorylated by ERK1/2, and it precipitated with ERK1/2 in a co
      immunoprecipitation assay, which suggests binding between ERK1/2 and nicastrin.
      Our results show that ERK1/2 is an endogenous regulator of gamma-secretase, which
      raises the possibility that ERK1/2 down-regulates gamma-secretase activity by
      directly phosphorylating nicastrin.

PMID- 16293709
TI  - The effect of p53-RNAi and p53 knockout on human 8-oxoguanine DNA glycosylase
      (hOgg1) activity.
AB  - Recent evidence indicates that in vitro p53 augments base excision repair (BER)
      activities in mammalian cells. To understand the role of p53 in BER, we analyzed
      the repair activity of hOgg1 in isogenic cell lines HCT116p53+/+ and HCT116p53-/
      . We found that hOgg1 activity was significantly decreased in HCT116p53-/- cells
      as compared with HCT116p53+/+ cells, indicating a functional role for p53 in the
      regulation of hOGG1. Using gel-shift assays, we showed that p53 binds to its
      putative cis-elements within the hOGG1 promoter. In addition we demonstrated that
      supplementing p53 in HCT116p53-/- cells enhanced the transcription of hOGG1. To
      further strengthen our findings, we used p53-RNAi to study the effects of
      decreased p53 levels on hOgg1 activity. We observed that p53-RNAi resulted in
      decreased hOGG1 expression both at the mRNA and protein levels. This decrease in
      hOGG1 expression was associated with reduced cell viability upon oxidative damage
      and reduced hOgg1 activity as evidenced by the 8-oxoG incision assay. Taken
      together, our results indicate that loss of p53 function can lead to decreased
      hOgg1 repair activity.

PMID- 16293710
TI  - Pretty subunits all in a row: using concatenated subunit constructs to force the
      expression of receptors with defined subunit stoichiometry and spatial
      arrangement.
AB  - The members of the Cys-loop ligand-gated ion channel (LGIC) gene family play a
      major role in fast synaptic transmission, and these receptors represent an
      important class of targets for therapeutic agents. Each member of this gene
      family is a pentameric complex containing one or more different subunits, and a
      large number of subunits for each member have been identified. This large number
      of subunits could give rise to a bewildering array of possible subunit
      compositions and spatial arrangements within a single complex, not all of which
      may occur in vivo. Heterologous expression systems have been used to create
      specific combinations of individual subunits to mimic naturally occurring
      receptors. However, this approach is not without its problems. In this issue of
      Molecular Pharmacology, Groot-Kormelink et al. (page 559) describe a method for
      constructing "concatameric" receptors, in which five individual subunits are
      arranged in a predetermined order connected by a flexible linker. Expression of
      this construct results in the formation of receptors with a unique, predefined
      subunit stoichiometry and subunit arrangement within the receptor complex.
      Receptors formed from this construct are fully functional and have properties
      essentially identical to those formed from individual subunits. The application
      of this very general approach to other members of the LGIC family should markedly
      enhance our ability to understand how subunit composition influences receptor
      function, as well as provide a means for the expression of receptors of
      predefined subunit composition and arrangement as tools for the development of
      novel selective pharmacological and therapeutic agents.

PMID- 16293711
TI  - Partial agonism, neutral antagonism, and inverse agonism at the human wild-type
      and constitutively active cholecystokinin-2 receptors.
AB  - Cholecystokinin receptor-2 (CCK2R) is a G protein receptor that regulates a
      number of physiological functions. Activation of CCK2R and/or expression of a
      constitutively active CCK2R variant may contribute to human diseases, including
      digestive cancers. Search for antagonists of the CCK2R has been an important
      challenge during the last few years, leading to discovery of a set of chemically
      distinct compounds. However, several early-discovered antagonists turned out to
      be partial agonists. In this context, we carried out pharmacological
      characterization of six CCK2R antagonists using COS-7 cells expressing the human
      CCK2R or a CCK2R mutant having a robust constitutive activity on inositol
      phosphates production, and we investigated the molecular mechanisms which, at a
      CCK2R binding site, account for these features. Results indicated that three
      compounds, 3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3
      yl)-N'-(3-methylphenyl)urea (L365,260), 4-{[2-[[3-(lH-indol-3-yl)-2-methyl-1-oxo
      2-[[[1.7.7-trimethyl-bicyclo[2.2.1]hept-2-yl)-oxy]carbonyl]amino]propyl]amino]-1
      phenylethyl]amino-4-oxo-[lS-la.2[S*(S*)]4a]}-butanoate N-methyl-D-glucamine
      (PD135,158), and (R)-1-naphthalenepropanoic acid, b-[2-[[2-(8-azaspiro-[4.5]dec-8
      ylcarbonyl)-4,6-dimethylphenyl]amino]-2-oxoethyl] (CR2945), were partial
      agonists; one molecule, 1-[(R)-2,3-dihydro-1-(2,3-dihydro-1-(2-methylphenacyl)-2
      oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022), was a
      neutral antagonist; and two compounds, N-(+)-[1-(adamant-1-ylmethyl)-2,4-dioxo-5
      phenyl2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl]-N'-phenylurea (GV150,013X)
      and ([(N-[methoxy-3 phenyl] N-[N-methyl N-phenyl carbamoylmethyl], carbomoyl
      methyl)-3 ureido]-3-phenyl)2-propionic acid (RPR101,048), were inverse agonists.
      Furthermore, target- and pharmacophore-based docking of ligands followed by
      molecular dynamic simulation experiments resulted in consistent motion of
      aromatic residues belonging to a network presumably important for activation,
      thus providing the first structural explanations for the different
      pharmacological profiles of tested compounds. This study confirms that several
      referenced so-called antagonists are in fact partial agonists, and because of
      this undesired activity, we suggest that newly generated molecules should be
      preferred to efficiently block CCK2R-related physiological effects. Furthermore,
      data on the structural basis for the different pharmacological features of CCK2R
      ligands will serve to further clarify CCK2R mechanism of activation.

PMID- 16293712
TI  - Relationship between temperature, dopaminergic neurotoxicity, and plasma drug
      concentrations in methamphetamine-treated squirrel monkeys.
AB  - To examine the relationship between temperature (ambient and core), dopaminergic
      neurotoxicity, and plasma drug [methamphetamine (METH)] and metabolite
      [amphetamine (AMPH)] concentrations, two separate groups of squirrel monkeys (n =
      4-5 per group) were treated with METH (1.25 mg/kg, given twice, 4 h apart) or
      vehicle (same schedule) at two different ambient temperatures (26 and 33 degrees
      C). Core temperatures and plasma drug concentrations were measured during the
      period of drug exposure; striatal monoaminergic neuronal markers in the same
      monkeys were determined 1 week later. At the temperature range examined, the
      higher ambient temperature did not significantly enhance METH-induced
      hyperthermia or METH-induced dopaminergic neurotoxicity, although there were
      trends toward increases. Acute METH-induced increases in core temperature
      correlated highly and directly with subsequent decreases in striatal dopaminergic
      markers. Squirrel monkeys with the greatest increases in core temperature (and
      largest dopaminergic deficits) had the highest plasma drug metabolite (AMPH)
      concentrations. There was substantial interanimal variability, both with regard
      to elevations in core temperature and plasma drug concentrations. Pharmacokinetic
      studies in six additional squirrel monkeys revealed comparable individual
      differences in METH metabolism. These results, which provide the first available
      data on the within-subject relationship between temperature (ambient and core),
      plasma concentrations of METH (and AMPH), and subsequent dopaminergic neurotoxic
      changes, suggest that, as in rodents, core temperature can influence METH
      neurotoxicity in primates. In addition, they suggest that interanimal differences
      presently observed in thermal and neurotoxic responses to METH may be related to
      individual differences in drug metabolism.

PMID- 16293713
TI  - Identification of the insulin signaling cascade in the regulation of alpha-class
      glutathione S-transferase expression in primary cultured rat hepatocytes.
AB  - We reported previously that insulin elevated alpha-class glutathione S
      transferase (GSTs) protein levels in primary cultured rat hepatocytes (Kim et
      al., 2003b). In contrast, glucagon down-regulated alpha- and pi-class GST
      expression, and mechanistic research implicated cAMP and protein kinase A in this
      process (Kim et al., 2003b). The present study examines the signaling pathways
      involved in the regulation of alpha-class GST in response to insulin in primary
      cultured rat hepatocytes. Protein levels of GSTA1/2 and GSTA3/5 and activity of
      GST toward 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD) were increased in an
      insulin concentration-dependent manner. Treatment of cells with the
      phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002 [2-(4
      morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] or rapamycin, an inhibitor of
      mammalian target of rapamycin and ribosomal p70 S6 kinase (p70S6K)
      phosphorylation, or with an adenovirus containing green fluorescent protein and a
      dominant-negative and kinase-dead Akt, effectively inhibited the insulin-mediated
      increase in alpha-class GST expression and GST activity toward NBD. In contrast,
      PD98059 (2'-amino-3'-methoxyflavone), an inhibitor of mitogen-activated protein
      kinase kinase, SP600125 (1,9-pyrazoloanthrone), an inhibitor of c-Jun N-terminal
      kinase, SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H
      imadazole], an inhibitor of p38 mitogen-activated protein kinase, or
      bisindolylmaleimide, a broad spectrum inhibitor of protein kinase C, did not
      inhibit the insulin-mediated increase in alpha-class GST protein levels in
      hepatocytes. These results show that PI3K/Akt/p70S6K signaling is active in the
      insulin-mediated up-regulation of the antioxidant defense system and that low
      insulin levels, as encountered in diabetes, potentially increase the
      susceptibility of hepatocytes to xenobiotic-mediated and/or oxidative stress
      mediated damage.

PMID- 16293714
TI  - Changes in pharmacokinetics of anti-HIV protease inhibitors during pregnancy: the
      role of CYP3A and P-glycoprotein.
AB  - Human immunodeficiency virus (HIV)-infected women have reduced exposure [area
      under the curve (AUC)] to anti-HIV protease inhibitors [e.g., nelfinavir (NFV)]
      during pregnancy. To determine the mechanistic basis of this phenomenon, we
      administered NFV mesylate orally (2.5 mg) or intravenously (0.625 mg) to timed
      pregnant (gestational age: 18-19 days) and non-pregnant FVB mice. After oral but
      not after i.v. administration, the plasma clearance of NFV was higher (by 134%, p
      < 0.05) and bioavailability was lower (by 32%, p < 0.05) in pregnant (n = 3)
      versus nonpregnant mice (n = 3). These effects of pregnancy were not due to
      changes in plasma protein binding of NFV. The half-life of NFV depletion in
      hepatic S-9 fractions of pregnant mice (n = 8) was 2.2-fold faster (p < 0.05)
      than that in nonpregnant mice (n = 7). Hepatic CYP3A activity (testosterone 6beta
      hydroxylation, n = 4) and expression (n = 8) were significantly higher (by 138
      and 49%, p < 0.05) in pregnant mice than that in nonpregnant mice. In the
      intestine, no CYP3A activity was detected and CYP3A protein expression (n = 6, p
      > 0.05) was not significantly different between the two groups. P-glycoprotein
      expression (n = 6) in hepatic and intestinal tissue of pregnant mice was not
      significantly different from that in nonpregnant mice. These changes in
      disposition of NFV during pregnancy are predominately due to a change in its
      bioavailability. An increase in hepatic CYP3A can explain the reduced
      bioavailability of NFV during pregnancy. If such upregulation of hepatic CYP3A
      activity occurs in pregnant women, it has important implications for dose
      adjustment of a variety of drugs ingested by pregnant women and cleared
      predominately via CYP3A metabolism.

PMID- 16293715
TI  - In vivo evaluation of P-glycoprotein function at the blood-brain barrier in
      nonhuman primates using [11C]verapamil.
AB  - P-glycoprotein (P-gp) is a major efflux transporter contributing to the efflux of
      a range of xenobiotic compounds at the blood-brain barrier (BBB). In the present
      study, we evaluated the P-gp function at the BBB using positron emission
      tomography (PET) in nonhuman primates. Serial brain PET scans were obtained in
      three rhesus monkeys after intravenous administration of [(11)C]verapamil under
      control and P-gp inhibition conditions ([PSC833 ([3'-keto-Me-Bmt(1)]-[Val(2)]
      cyclosporin) 20 mg/kg/2 h]). The parent [(11)C]verapamil and its metabolites in
      plasma were determined by HPLC with a positron detector. The initial brain uptake
      clearance calculated from the integration plot was used for the quantitative
      analysis. After intravenous administration, [(11)C]verapamil was taken up rapidly
      into the brain (time to reach the peak, 0.58 min). The blood level of
      [(11)C]verapamil decreased rapidly, and it underwent metabolism with time. The
      inhibition of P-gp by PSC833 increased the brain uptake of [(11)C]verapamil 4.61
      fold (0.141 versus 0.651 ml/g brain/min, p < 0.05). These results suggest that
      PET measurement with [(11)C]verapamil can be used for the evaluation of P-gp
      function at the BBB in the living brain.

PMID- 16293717
TI  - Cardiorespiratory fitness is an independent predictor of hypertension incidence
      among initially normotensive healthy women.
AB  - The authors examined the association between cardiorespiratory fitness and
      incident hypertension in women who were normotensive and free of cardiovascular
      disease at baseline in the Aerobics Center Longitudinal Study (Dallas, Texas),
      1970-1998. A total of 4,884 women performed a maximal treadmill exercise test and
      completed a follow-up health survey. During an average follow-up of 5 years, 157
      incident cases of self-reported, physician-diagnosed hypertension were identified
      from the health surveys. The cumulative incidence of hypertension was 3.2%.
      Compared with the rates of low-fit women, crude hypertension rates were 60% and
      79% lower among women in the moderate and high fitness categories, respectively
      (p < 0.001). After adjustment for several potential confounders, the odds ratios
      for hypertension were 1.0, 0.61 (95% confidence interval (CI): 0.30, 1.21), and
      0.35 (95% CI: 0.17, 0.73) in low-, moderately, and highly fit women, respectively
      (p(trend) < 0.01). Each 1-metabolic equivalent increment in treadmill performance
      was, on average, associated with a 19% (95% CI: 10, 27; p < 0.001) lower odds of
      incident hypertension. The pattern and strength of association between fitness
      and hypertension persisted in analyses stratified on body mass index, age, and
      the presence of prehypertension at baseline. An active lifestyle should be
      promoted for the primary prevention of hypertension in women.

PMID- 16293716
TI  - Heart disease and dementia: a population-based study.
AB  - There are conflicting reports on the possible positive association between
      coronary disease and dementia. The objectives of this study were to examine the
      association between coronary disease, as measured by myocardial infarction and
      cardiac death, and dementia in a population-based study. By use of the record
      linkage system of the Rochester Epidemiology Project, 916 cases of dementia and
      916 age (+/-1 year)- and sex-matched controls were identified in Rochester,
      Minnesota, between 1985 and 1994. From the same population, the authors
      identified all subjects who experienced a myocardial infarction (defined using
      standardized criteria) during the period 1979-1998. For myocardial infarction
      occurring prior to the index year of dementia, the authors used conditional
      logistic regression (case-control analysis), while for myocardial infarction and
      death occurring after the index year, they used competing risk survival analysis
      to account for informative censoring (cohort analysis). Before the index year,
      the odds ratio for myocardial infarction among cases with dementia compared with
      controls was 1.00 (95% confidence interval (CI): 0.62, 1.62; p = 1.00). After the
      index year, patients with dementia had a 46% decreased risk of subsequent
      myocardial infarction (hazard ratio = 0.54, 95% CI: 0.36, 0.82; p = 0.004) and an
      18% decreased risk of cardiac death (hazard ratio = 0.82, 95% CI: 0.70, 0.95; p =
      0.010). There was no evidence of a positive association between dementia and
      preceding myocardial infarction, while there was a decreased risk of myocardial
      infarction and cardiac death following dementia.

PMID- 16293718
TI  - Estimating the proportion of disease due to classes of sufficient causes.
AB  - Disease can be caused by different mechanisms. A possible causal model proposed
      by Rothman is a complete causal mechanism or a so-called "sufficient cause"
      consisting of a set of component causes that can be illustrated in a pie chart.
      However, this model does not allow finding out what sufficient causes produce the
      majority of cases. The authors' objective was to extend Rothman's work by
      quantifying the proportion of disease that can be attributed to a class of
      sufficient causes. The underlying idea was to consider all combinations of a
      given set of known risk factors and to assign each combination to a class of
      sufficient causes. This assignment makes it possible to evaluate a class of
      sufficient causes by the population attributable fraction of the corresponding
      combination of risk factors. The approach presented was applied to sufficient
      causes of myocardial infarction by use of data on participants recruited between
      1994 and 1998 into the European Prospective Investigation into Cancer and
      Nutrition-Potsdam Study. As a result, 51.8% of cases were attributed to only four
      different classes of sufficient causes. In conclusion, the statistical method
      described in the paper may be beneficial for quantifying the importance of
      different sufficient causes and for improving the efficiency of public health
      programs.

PMID- 16293719
TI  - Chronic multisymptom illness complex in Gulf War I veterans 10 years later.
AB  - Prior research has demonstrated that shortly after the 1991 Gulf War (Gulf War
      I), chronic multisymptom illness (CMI) was more common among deployed veterans
      than among nondeployed veterans. The aims of the current study were to determine
      the prevalence of CMI among deployed and nondeployed veterans 10 years after Gulf
      War I, compare the distribution of comorbid conditions, and identify prewar
      factors associated with CMI. Cross-sectional data collected from 1,061 deployed
      veterans and 1,128 nondeployed veterans examined between 1999 and 2001 were
      analyzed. CMI prevalence was 28.9% among deployed veterans and 15.8% among
      nondeployed veterans (odds ratio = 2.16, 95% confidence interval: 1.61, 2.90).
      Deployed and nondeployed veterans with CMI had similarly poorer quality-of-life
      measures and higher prevalences of symptom-based medical conditions, metabolic
      syndrome, and psychiatric disorders. Diagnoses of prewar anxiety disorders (not
      related to post-traumatic stress disorder) and depression were associated with
      CMI among both deployed and nondeployed veterans. Nicotine dependence and veteran
      reported physician-diagnosed infectious mononucleosis were associated with CMI
      among deployed veterans, and migraine headaches and gastritis were associated
      with CMI among nondeployed veterans. CMI continues to be substantially more
      prevalent among deployed veterans than among nondeployed veterans 10 years after
      Gulf War I, but it manifests similarly in both groups. It is likely to be a
      common, persistent problem among veterans returning from the current Gulf War.

PMID- 16293720
TI  - A strong secular trend in serum gamma-glutamyltransferase from 1996 to 2003 among
      South Korean men.
AB  - Serum gamma-glutamyltransferase (GGT) concentration, within its normal range, has
      recently been proposed as a reliable marker of oxidative stress. Oxidative stress
      plays a central pathogenic role in many metabolic and/or cardiovascular diseases,
      incidences of which have recently increased in South Korea. Since serum GGT has
      strong associations with these diseases and their risk factors, the authors
      hypothesized a corresponding secular trend of increasing serum GGT levels in
      South Korea. Study subjects were 8,072 male workers at a large steel company who
      were aged 24-44 years at baseline and had received annual physical examinations
      from 1996 to 2003. The secular trend was a 0.1066-units/liter increase in ln(GGT)
      level per calendar year (a 180% increase during the 7-year follow-up period) (p <
      0.01). Adjustment for body mass index, alcohol consumption, smoking, exercise,
      and cholesterol level as time-dependent covariates did not change the results.
      Although cholesterol is commonly used as a marker of epidemiologic transition,
      there was a less dramatic secular trend in ln(serum cholesterol) level, and it
      disappeared after adjustment for the secular trend in serum GGT. These findings
      suggest that serum GGT concentration can be used as a sensitive marker of
      epidemiologic transition, and they portend a continuing rise in incidences of
      metabolic and/or cardiovascular diseases in this population in the coming years.

PMID- 16293721
TI  - Heterogeneous Hadean hafnium: evidence of continental crust at 4.4 to 4.5 ga.
AB  - The long-favored paradigm for the development of continental crust is one of
      progressive growth beginning at approximately 4 billion years ago (Ga). To test
      this hypothesis, we measured initial 176Hf/177Hf values of 4.01- to 4.37-Ga
      detrital zircons from Jack Hills, Western Australia. epsilonHf (deviations of
      176Hf/177Hf from bulk Earth in parts per 10(4)) values show large positive and
      negative deviations from those of the bulk Earth. Negative values indicate the
      development of a Lu/Hf reservoir that is consistent with the formation of
      continental crust (Lu/Hf approximately 0.01), perhaps as early as 4.5 Ga.
      Positive epsilon(Hf) deviations require early and likely widespread depletion of
      the upper mantle. These results support the view that continental crust had
      formed by 4.4 to 4.5 Ga and was rapidly recycled into the mantle.

PMID- 16293722
TI  - Evidence for macromolecular protein rings in the absence of bulk water.
AB  - We have examined the architecture of a protein complex in the absence of bulk
      water. By determining collision cross sections of assemblies of the trp RNA
      binding protein, TRAP, we established that the 11-membered ring topology of the
      complex can be maintained within a mass spectrometer. We also found that the
      binding of tryptophan enhances the stability of the ring structure and that
      addition of a specific RNA molecule increases the size of the complex and
      prevents structural collapse. These results provide definitive evidence that
      protein quaternary structure can be maintained in the absence of bulk water and
      highlight the potential of ion mobility separation for defining shapes of
      heterogeneous macromolecular assemblies.

PMID- 16293725
TI  - Not just jobs: ScienceCareers.org.

PMID- 16293726
TI  - Stem cells. Collaborators split over ethics allegations.

PMID- 16293724
TI  - Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin
      signaling axis.
AB  - How cyclooxygenase-2 (COX-2) and its proinflammatory metabolite prostaglandin E2
      (PGE2) enhance colon cancer progression remains poorly understood. We show that
      PGE2 stimulates colon cancer cell growth through its heterotrimeric guanine
      nucleotide-binding protein (G protein)-coupled receptor, EP2, by a signaling
      route that involves the activation of phosphoinositide 3-kinase and the protein
      kinase Akt by free G protein betagamma subunits and the direct association of the
      G protein alphas subunit with the regulator of G protein signaling (RGS) domain
      of axin. This leads to the inactivation and release of glycogen synthase kinase
      3beta from its complex with axin, thereby relieving the inhibitory
      phosphorylation of beta-catenin and activating its signaling pathway. These
      findings may provide a molecular framework for the future evaluation of
      chemopreventive strategies for colorectal cancer.

PMID- 16293723
TI  - Glial membranes at the node of Ranvier prevent neurite outgrowth.
AB  - Nodes of Ranvier are regularly placed, nonmyelinated axon segments along
      myelinated nerves. Here we show that nodal membranes isolated from the central
      nervous system (CNS) of mammals restricted neurite outgrowth of cultured neurons.
      Proteomic analysis of these membranes revealed several inhibitors of neurite
      outgrowth, including the oligodendrocyte myelin glycoprotein (OMgp). In rat
      spinal cord, OMgp was not localized to compact myelin, as previously thought, but
      to oligodendroglia-like cells, whose processes converge to form a ring that
      completely encircles the nodes. In OMgp-null mice, CNS nodes were abnormally wide
      and collateral sprouting was observed. Nodal ensheathment in the CNS may
      stabilize the node and prevent axonal sprouting.

PMID- 16293728
TI  - POLITICS. Antiterror law intrusive, U.K. academic groups warn.

PMID- 16293727
TI  - U.S. higher education. Professor sues university over building he is funding.

PMID- 16293729
TI  - African science. A move to revamp elite institutions across the continent.

PMID- 16293731
TI  - Neuroscience. Neuroscientists welcome Dalai Lama with mostly open arms.

PMID- 16293730
TI  - Influenza. Meeting seeks global consensus, highlights global disparities.

PMID- 16293733
TI  - Energy supplies. Bumpy road ahead for world's oil.

PMID- 16293732
TI  - Teaching evolution. Antievolutionists win one in Kansas, lose eight seats in
      Dover.

PMID- 16293734
TI  - Energy supplies. If not cheap oil ...

PMID- 16293735
TI  - Developmental basis of evolution meeting. Hummingbirds keep plant speciation
      humming along.

PMID- 16293736
TI  - Developmental basis of evolution meeting. Development out of sync.

PMID- 16293737
TI  - Edward Ames profile. Uncovering the hidden paths of Maine's threatened cod.

PMID- 16293738
TI  - Avian influenza. Pandemic skeptics warn against crying wolf.

PMID- 16293739
TI  - New directions in plastic debris.

PMID- 16293740
TI  - Preparing for the worst-case scenario.

PMID- 16293741
TI  - Timing in collection of stool samples.

PMID- 16293742
TI  - Epidemiology. DNA identifications after the 9/11 World Trade Center attack.
AB  - The attack on the World Trade Center on 9/11/2001 challenged current approaches
      to forensic DNA typing methods. The large number of victims and the extreme
      thermal and physical conditions of the site necessitated special approaches to
      the DNA-based identification. Because of these and many additional challenges,
      new procedures were created or modified from routine forensic protocols. This
      effort facilitated the identification of 1594 of the 2749 victims. In this Policy
      Forum, the authors, who were were members of the World Trade Center Kinship and
      Data Analysis Panel, review the lessons of the attack response from the
      perspective of DNA forensic identification and suggest policies and procedures
      for future mass disasters or large-scale terrorist attacks.

PMID- 16293743
TI  - Cell biology. Twists in the tale of the aging yeast.

PMID- 16293744
TI  - Geochemistry. A stranger in paradise.

PMID- 16293745
TI  - Paleontology. Dinosaurs dined on grass.

PMID- 16293746
TI  - Genetics. Two genes link two distinct psychoses.

PMID- 16293748
TI  - Materials and biology. Nanotechnology takes aim at cancer.

PMID- 16293749
TI  - Exploring and engineering the cell surface interface.
AB  - Cells are inherently sensitive to local mesoscale, microscale, and nanoscale
      patterns of chemistry and topography. We review current approaches to control
      cell behavior through the nanoscale engineering of materials surfaces. Far
      reaching implications are emerging for applications including medical implants,
      cell supports, and materials that can be used as instructive three-dimensional
      environments for tissue regeneration.

PMID- 16293750
TI  - Tissue cells feel and respond to the stiffness of their substrate.
AB  - Normal tissue cells are generally not viable when suspended in a fluid and are
      therefore said to be anchorage dependent. Such cells must adhere to a solid, but
      a solid can be as rigid as glass or softer than a baby's skin. The behavior of
      some cells on soft materials is characteristic of important phenotypes; for
      example, cell growth on soft agar gels is used to identify cancer cells. However,
      an understanding of how tissue cells-including fibroblasts, myocytes, neurons,
      and other cell types-sense matrix stiffness is just emerging with quantitative
      studies of cells adhering to gels (or to other cells) with which elasticity can
      be tuned to approximate that of tissues. Key roles in molecular pathways are
      played by adhesion complexes and the actinmyosin cytoskeleton, whose contractile
      forces are transmitted through transcellular structures. The feedback of local
      matrix stiffness on cell state likely has important implications for development,
      differentiation, disease, and regeneration.

PMID- 16293751
TI  - Rigid biological systems as models for synthetic composites.
AB  - Advances that have been made in understanding the mechanisms underlying the
      mechanical behavior of a number of biological materials (namely mollusk shells
      and sponge spicules) are discussed here. Attempts at biomimicry of the structure
      of a nacreous layer of a mollusk shell have shown reasonable success. However,
      they have revealed additional issues that must be addressed if new synthetic
      composite materials that are based on natural systems are to be constructed. Some
      of the important advantages and limitations of copying from nature are also
      described here.

PMID- 16293752
TI  - Inspirations from biological optics for advanced photonic systems.
AB  - Observing systems in nature has inspired humans to create technological tools
      that allow us to better understand and imitate biology. Biomimetics, in
      particular, owes much of its current development to advances in materials science
      and creative optical system designs. New investigational tools, such as those for
      microscopic imaging and chemical analyses, have added to our understanding of
      biological optics. Biologically inspired optical science has become the emerging
      topic among researchers and scientists. This is in part due to the availability
      of polymers with customizable optical properties and the ability to rapidly
      fabricate complex designs using soft lithography and three-dimensional microscale
      processing techniques.

PMID- 16293753
TI  - Directionally controlled fluorescence emission in butterflies.
AB  - Recently developed, high-efficiency, light-emitting diodes use two-dimensional
      photonic crystals to enhance the extraction of otherwise internally trapped light
      and multilayer reflectors to control the direction of light emission. This work
      describes the characterization of a naturally evolved light-extraction system on
      the wing scales of a small group of Papilio butterflies. The efficient extraction
      of fluorescence from these scales is facilitated by a two-dimensional photonic
      crystal slab that uses a multilayer to help control emission direction. Its light
      extraction function is analogous to that of the light-emitting diode.

PMID- 16293754
TI  - Structure of the quaternary complex of interleukin-2 with its alpha, beta, and
      gammac receptors.
AB  - Interleukin-2 (IL-2) is an immunoregulatory cytokine that acts through a
      quaternary receptor signaling complex containing alpha (IL-2Ralpha), beta (IL
      2Rbeta), and common gamma chain (gc) receptors. In the structure of the
      quaternary ectodomain complex as visualized at a resolution of 2.3 angstroms, the
      binding of IL-2Ralpha to IL-2 stabilizes a secondary binding site for
      presentation to IL-2Rbeta. gammac is then recruited to the composite surface
      formed by the IL-2/IL-2Rbeta complex. Consistent with its role as a shared
      receptor for IL-4, IL-7, IL-9, IL-15, and IL-21, gammac forms degenerate contacts
      with IL-2. The structure of gammac provides a rationale for loss-of-function
      mutations found in patients with X-linked severe combined immunodeficiency
      diseases (X-SCID). This complex structure provides a framework for other gammac
      dependent cytokine-receptor interactions and for the engineering of improved IL-2
      therapeutics.

PMID- 16293755
TI  - Thermodynamics of an incommensurate quantum crystal.
AB  - We present a theory of the thermodynamics of an incommensurate quantum solid. The
      ground state of the solid is assumed to be an incommensurate crystal, with
      quantum zero-point vacancies and interstitials and thus a non-integer number of
      atoms per unit cell. We show that at low temperature T, the variation of the net
      vacancy concentration should be as T4 and that the first correction to the
      specific heat due to this varies as T7; these are quite consistent with
      experiments on solid helium-4. We also make some observations about the recent
      experimental reports of "supersolidity" in solid helium-4 that motivate a renewed
      interest in quantum crystals.

PMID- 16293756
TI  - Porous, crystalline, covalent organic frameworks.
AB  - Covalent organic frameworks (COFs) have been designed and successfully
      synthesized by condensation reactions of phenyl diboronic acid {C6H4[B(OH)2]2}
      and hexahydroxytriphenylene [C18H6(OH)6]. Powder x-ray diffraction studies of the
      highly crystalline products (C3H2BO)6.(C9H12)1 (COF-1) and C9H4BO2 (COF-5)
      revealed expanded porous graphitic layers that are either staggered (COF-1,
      P6(3)/mmc) or eclipsed (COF-5, P6/mmm). Their crystal structures are entirely
      held by strong bonds between B, C, and O atoms to form rigid porous architectures
      with pore sizes ranging from 7 to 27 angstroms. COF-1 and COF-5 exhibit high
      thermal stability (to temperatures up to 500 degrees to 600 degrees C), permanent
      porosity, and high surface areas (711 and 1590 square meters per gram,
      respectively).

PMID- 16293757
TI  - Bright infrared emission from electrically induced excitons in carbon nanotubes.
AB  - We used the high local electric fields at the junction between the suspended and
      supported parts of a single carbon nanotube molecule to produce unusually bright
      infrared emission under unipolar operation. Carriers were accelerated by band
      bending at the suspension interface, and they created excitons that radiatively
      recombined. This excitation mechanism is approximately 1000 times more efficient
      than recombination of independently injected electrons and holes, and it results
      from weak electron-phonon scattering and strong electron-hole binding caused by
      one-dimensional confinement. The ensuing high excitation density allows us to
      observe emission from higher excited states not seen by photoexcitation. The
      excitation mechanism of these states was analyzed.

PMID- 16293758
TI  - Retention of xenon in quartz and Earth's missing xenon.
AB  - The reactivity of xenon with terrestrial oxides was investigated by in situ
      synchrotron x-ray diffraction. At high temperature (T > 500 kelvin), some silicon
      was reduced, and the pressure stability of quartz was expanded, attesting to the
      substitution of some xenon for silicon. When the quartz was quenched, xenon
      diffused out and only a few weight percent remained trapped in samples. These
      results show that xenon can be covalently bonded to oxygen in quartz in the lower
      continental crust, providing an answer to the missing xenon problem; synthesis
      paths of rare gas compounds are also opened.

PMID- 16293759
TI  - Dinosaur coprolites and the early evolution of grasses and grazers.
AB  - Silicified plant tissues (phytoliths) preserved in Late Cretaceous coprolites
      from India show that at least five taxa from extant grass (Poaceae) subclades
      were present on the Indian subcontinent during the latest Cretaceous. This
      taxonomic diversity suggests that crown-group Poaceae had diversified and spread
      in Gondwana before India became geographically isolated. Other phytoliths
      extracted from the coprolites (from dicotyledons, conifers, and palms) suggest
      that the suspected dung producers (titanosaur sauropods) fed indiscriminately on
      a wide range of plants. These data also make plausible the hypothesis that
      gondwanatherian mammals with hypsodont cheek teeth were grazers.

PMID- 16293760
TI  - Pre- and postinvasion defenses both contribute to nonhost resistance in
      Arabidopsis.
AB  - Nonhost resistance describes the immunity of an entire plant species against
      nonadapted pathogen species. We report that Arabidopsis PEN2 restricts pathogen
      entry of two ascomycete powdery mildew fungi that in nature colonize grass and
      pea species. The PEN2 glycosyl hydrolase localizes to peroxisomes and acts as a
      component of an inducible preinvasion resistance mechanism. Postinvasion fungal
      growth is blocked by a separate resistance layer requiring the EDS1-PAD4-SAG101
      signaling complex, which is known to function in basal and resistance (R) gene
      triggered immunity. Concurrent impairment of pre- and postinvasion resistance
      renders Arabidopsis a host for both nonadapted fungi.

PMID- 16293761
TI  - GTF2IRD1 in craniofacial development of humans and mice.
AB  - Craniofacial abnormalities account for about one-third of all human congenital
      defects, but our understanding of the genetic mechanisms governing craniofacial
      development is incomplete. We show that GTF2IRD1 is a genetic determinant of
      mammalian craniofacial and cognitive development, and we implicate another member
      of the TFII-I transcription factor family, GTF2I, in both aspects. Gtf2ird1-null
      mice exhibit phenotypic abnormalities reminiscent of the human microdeletion
      disorder Williams-Beuren syndrome (WBS); craniofacial imaging reveals
      abnormalities in both skull and jaws that may arise through misregulation of
      goosecoid, a downstream target of Gtf2ird1. In humans, a rare WBS individual with
      an atypical deletion, including GTF2IRD1, shows facial dysmorphism and cognitive
      deficits that differ from those of classic WBS cases. We propose a mechanism of
      cumulative dosage effects of duplicated and diverged genes applicable to other
      human chromosomal disorders.

PMID- 16293762
TI  - DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate
      cAMP signaling.
AB  - The disrupted in schizophrenia 1 (DISC1) gene is a candidate susceptibility
      factor for schizophrenia, but its mechanistic role in the disorder is unknown.
      Here we report that the gene encoding phosphodiesterase 4B (PDE4B) is disrupted
      by a balanced translocation in a subject diagnosed with schizophrenia and a
      relative with chronic psychiatric illness. The PDEs inactivate adenosine 3',5'
      monophosphate (cAMP), a second messenger implicated in learning, memory, and
      mood. We show that DISC1 interacts with the UCR2 domain of PDE4B and that
      elevation of cellular cAMP leads to dissociation of PDE4B from DISC1 and an
      increase in PDE4B activity. We propose a mechanistic model whereby DISC1
      sequesters PDE4B in resting cells and releases it in an activated state in
      response to elevated cAMP.

PMID- 16293763
TI  - Altered TCR signaling from geometrically repatterned immunological synapses.
AB  - The immunological synapse is a specialized cell-cell junction that is defined by
      large-scale spatial patterns of receptors and signaling molecules yet remains
      largely enigmatic in terms of formation and function. We used supported bilayer
      membranes and nanometer-scale structures fabricated onto the underlying substrate
      to impose geometric constraints on immunological synapse formation. Analysis of
      the resulting alternatively patterned synapses revealed a causal relation between
      the radial position of T cell receptors (TCRs) and signaling activity, with
      prolonged signaling from TCR microclusters that had been mechanically trapped in
      the peripheral regions of the synapse. These results are consistent with a model
      of the synapse in which spatial translocation of TCRs represents a direct
      mechanism of signal regulation.

PMID- 16293764
TI  - Regulation of yeast replicative life span by TOR and Sch9 in response to
      nutrients.
AB  - Calorie restriction increases life span in many organisms, including the budding
      yeast Saccharomyces cerevisiae. From a large-scale analysis of 564 single-gene
      deletion strains of yeast, we identified 10 gene deletions that increase
      replicative life span. Six of these correspond to genes encoding components of
      the nutrient-responsive TOR and Sch9 pathways. Calorie restriction of tor1D or
      sch9D cells failed to further increase life span and, like calorie restriction,
      deletion of either SCH9 or TOR1 increased life span independent of the Sir2
      histone deacetylase. We propose that the TOR and Sch9 kinases define a primary
      conduit through which excess nutrient intake limits longevity in yeast.

PMID- 16293765
TI  - Embryonic lethality in Dear gene-deficient mice: new player in angiogenesis.
AB  - The dual endothelin-1/angiotensin II receptor (Dear) binds endothelin-1 (ET-1)
      and angiotensin II (ANG II) with equal affinities in the Dahl S/JRHS rat strain.
      To elucidate its physiological significance within the context of multiple
      receptor isoforms and diverse ET-1 and ANG II functions spanning blood pressure
      regulation, tumor proliferation, and angiogenesis, we characterized mouse Dear
      and Dear-deficient mice. Unlike null mutant models of ET-1, ANG II, and all other
      ET-1 and ANG II receptors, Dear(-/-) deficiency results in impaired angiogenesis,
      dysregulated neuroepithelial development, and embryonic lethality by embryonic
      day 12.5. Interestingly, mouse Dear does not bind ANG II, similar to Dahl R/JRHS
      rat Dear, but binds ET-1 and vascular endothelial growth factor (VEGF) signal
      peptide (VEGFsp) with equal affinities, suggesting a putative novel multifunction
      for VEGFsp and a parsimonious mechanism for coordination of VEGF-induced and Dear
      mediated pathways. Consistent with its developmental angiogenic role, Dear
      inhibition results in decreased tumor growth in B16-F10 melanoma cell-induced
      subcutaneous tumor in female Dear(+/-)/C57BL6BC10 mice, but not in males (age 3.5
      mo), and in 127Cs radiation-induced orthotopic mammary tumors in Sprague-Dawley
      female rats (age range 3-6.5 mo). Altogether, the data identify Dear as a new
      player in angiogenesis during development downstream to, and nonredundant with,
      VEGF-mediated pathways, as well as a putative modulator of tumor angiogenesis
      acting within a gender-specific paradigm.

PMID- 16293766
TI  - Is dehydroepiandrosterone a hormone?
AB  - Dehydroepiandrosterone (DHEA) is not a hormone but it is a very important
      prohormone secreted in large amounts by the adrenals in humans and other
      primates, but not in lower species. It is secreted in larger quantities than
      cortisol and is present in the blood at concentrations only second to
      cholesterol. All the enzymes required to transform DHEA into androgens and/or
      estrogens are expressed in a cell-specific manner in a large series of peripheral
      target tissues, thus permitting all androgen-sensitive and estrogen-sensitive
      tissues to make locally and control the intracellular levels of sex steroids
      according to local needs. This new field of endocrinology has been called
      intracrinology. In women, after menopause, all estrogens and almost all androgens
      are made locally in peripheral tissues from DHEA which indirectly exerts effects,
      among others, on bone formation, adiposity, muscle, insulin and glucose
      metabolism, skin, libido and well-being. In men, where the secretion of androgens
      by the testicles continues for life, the contribution of DHEA to androgens has
      been best evaluated in the prostate where about 50% of androgens are made locally
      from DHEA. Such knowledge has led to the development of combined androgen
      blockade (CAB), a treatment which adds a pure anti-androgen to medical (GnRH
      agonist) or surgical castration in order to block the access of the androgens
      made locally to the androgen receptor. In fact, CAB has been the first treatment
      demonstrated to prolong life in advanced prostate cancer while recent data
      indicate that it can permit long-term control and probably cure in at least 90%
      of cases of localized prostate cancer. The new field of intracrinology or local
      formation of sex steroids from DHEA in target tissues has permitted major
      advances in the treatment of the two most frequent cancers, namely breast and
      prostate cancer, while its potential use as a physiological HRT could well
      provide a physiological balance of androgens and estrogens, thus offering
      exciting possibilities for women's health at menopause.

PMID- 16293767
TI  - Up-regulation of rat myometrial phospholipases C{beta}1 and C{beta}3 correlates
      with increased term sensitivity to carbachol and oxytocin.
AB  - In the present study, we compared rat uterine contractility and myometrial
      inositol phosphate (InsP) production in response to activation of muscarinic and
      oxytocin receptors during pregnancy and at term. The level of myometrial
      phospholipase (PL) Cbeta was also determined by Western blotting at different
      stages of pregnancy and following administration of oestradiol, progesterone or
      vehicle. The results showed an increased potency of carbachol (CCh), a
      cholinergic muscarinic agonist, and oxytocin (OT) to enhance myometrial InsP
      production at term. This correlated with an increased potency of both agonists to
      induce contraction of the circular but not the longitudinal muscle. For both InsP
      production and contractile activity, the maximal response of CCh was unaltered,
      while that of OT was significantly increased. Interestingly, the increased
      responsiveness to CCh and OT was associated with an up-regulation of PLCbeta1 and
      PLCbeta3 enzymes. Such regulation is under the control of oestradiol since
      administration of this steroid to pregnant rats increased the amount of both
      enzymes by 200-260%. In contrast, progesterone administration was without effect.
      The present study presents the first evidence that the expression of rat
      myometrial PLCbeta1 and PLCbeta3 is under the positive control of oestradiol.
      This could participate in the enhancement of myometrial InsP accumulation and
      uterine contraction at term in response to CCh and OT. Based on contraction
      studies, we also propose that the longitudinal and circular uterine muscles
      differ in the regulation of the PLC pathway during pregnancy.

PMID- 16293768
TI  - Seasonal variation in expression and localization of testicular transforming
      growth factors TGF-{beta}1 and TGF-{beta}3 corresponds with spermatogenic
      activity in roe deer.
AB  - Adult roe deer males show hormonally controlled seasonal cycles of testicular
      growth and involution. Mediation of endocrine signals likely requires variable
      production of testicular growth factors for regulation of testis function. Here
      we studied the expression pattern of transforming growth factors (TGFs) beta1 and
      beta3. Total RNA from testis parenchyma was extracted monthly and analysed using
      quantitative reverse transcriptase PCR. The localization of mRNAs was determined
      by in situ hybridization, and corresponding proteins were visualized
      immunohistochemically. Both factors showed different expression levels and
      different seasonal expression patterns. The TGF-beta1 mRNA content was up to 45
      times higher than that of TGF-beta3. Compared with its lowest level in May, TGF
      beta1 expression was slightly enhanced during pre-rut (June/July). TGF-beta3
      expression increased 5-fold from April to June/July and decreased thereafter to
      its low in December. This corresponded with changing numbers of spermatocytes and
      round spermatids, in which both TGF-beta3 mRNA and the protein were mainly
      localized. The TGF-beta1 mRNA was found in interstitial cells, mainly during the
      non-breeding season, but also in spermatocytes and spermatids during activated
      spermatogenesis. The translation product was localized in few spermatogenic cells
      only. The results suggest that TGF-beta1 and -beta3 are important in regulating
      seasonal spermatogenesis of roe deer with diverse functions affecting
      interstitial and spermatogenic cells.

PMID- 16293769
TI  - Protective effect of testosterone on early apoptotic damage induced by
      streptozotocin in rat pancreas.
AB  - Beta-cell apoptosis is responsible for the development of insulin-dependent
      diabetes mellitus in the streptozotocin (STZ) rat model. It has been demonstrated
      that steroid hormones possess antioxidant and protective antiapoptotic effects in
      many tissues. The aim of the present study was to investigate the early apoptotic
      damage induced by STZ in rat pancreas, and the effect of testosterone in
      preventing apoptosis of pancreatic beta cells. Intact and castrated adult male
      Wistar rats were subjected to a unique injection of STZ 60 mg/kg (body weight) in
      citrate buffer, and the kinetics of apoptosis in beta cells was assessed. Insulin
      and glucose were measured by RIA and a glucometer respectively, and in pancreatic
      tissue by immunohistochemistry. At 6 h after STZ injection, a marked increase in
      apoptotic beta cells was detected; however, glucose and insulin serum levels were
      not significantly different from the controls. The castrated animals presented
      higher percentages of apoptotic beta cells (65.75 +/- 5.42%) than intact males
      (20.6 +/- 4.38%) and castrated, testosterone-substituted males (30.66 +/- 1.38%).
      The decrease in apoptotic beta cells induced by testosterone was reversed by the
      antiandrogen flutamide (67.69 +/- 3.45%). The overall results indicate that early
      apoptotic damage produced by STZ in castrated animals was reversed by
      testosterone, suggesting that this hormone exerts a natural protective effect in
      rat pancreas. This effect could help to explain some sexual differences in
      diabetes mellitus incidence in man, reinforcing the idea that new approaches in
      steroid hormone therapies should be considered for treatment of this disease.

PMID- 16293770
TI  - Over-expression of AMP-activated protein kinase impairs pancreatic {beta}-cell
      function in vivo.
AB  - Treatment of type 1 diabetes by islet transplantation is currently limited by
      loss of functional beta-cell mass after transplantation. We investigated here
      whether adenovirus-mediated changes in AMP-activated protein kinase (AMPK)
      activity, previously shown to affect insulin secretion in vitro, might affect
      islet graft function in vivo. In isolated mouse and rat islets, insulin secretion
      stimulated by 17 (vs 3) mmol/l glucose was inhibited by 36.5% (P<0.01) and 43%
      (P<0.02) respectively after over-expression of constitutively-active AMPK- (AMPK
      CA) versus null (eGFP-expressing) viruses, and glucose oxidation was decreased by
      38% (P<0.05) and 26.6% (P<0.05) respectively. Increases in apoptotic index
      (terminal deoxynucleotide transferase-mediated deoxyuridine trisphosphate biotin
      nick end-labelling) (TUNEL)) were also observed in AMPK CA- (22.8 +/- 3.6% TUNEL
      positive cells, P<0.001), but not AMPK DN- (2.72 +/- 3.9%, positive cells,
      P=0.05) infected islets, versus null adenovirus-treated islets (0.68 +/- 0.36%
      positive cells). Correspondingly, transplantation of islets expressing AMPK CA
      into streptozotocin-diabetic C57 BL/6 mice improved glycaemic control less
      effectively than transplantation with either null (P<0.02) or AMPK-DN-infected
      (P<0.01) islets. We conclude that activation of AMPK inhibits beta-cell function
      in vivo and may represent a target for therapeutic intervention during islet
      transplantation.

PMID- 16293771
TI  - Streptozotocin (STZ) mediates acute upregulation of serum and pancreatic
      osteopontin (OPN): a novel islet-protective effect of OPN through inhibition of
      STZ-induced nitric oxide production.
AB  - Osteopontin (OPN) is a secreted acidic phosphoprotein that binds to a cell
      surface integrin-binding motif and is involved in many inflammatory and immune
      modulating disorders. There is compelling evidence that soluble OPN can in a
      variety of situations help cells survive an otherwise lethal insult. In this
      study we show that OPN is localized in the rat pancreatic islets and ducts.
      Staining of pancreatic serial sections with islet hormone antibodies showed that
      all islet cells express OPN. Rats treated with a single dose of streptozotocin
      (STZ; 50 mg/kg) showed acute upregulation of serum OPN levels and pancreatic OPN
      mRNA and protein. Serum OPN dropped by the end of day 7 but was still higher than
      prediabetic levels. Pancreatic mRNA and protein showed a similar pattern. Twenty
      four hours after STZ injection, the intensified OPN expression was localized
      towards the periphery of the islets and surrounded the remaining insulin-positive
      cells. To explore the significance of OPN acute upregulation, freshly isolated
      islets were pretreated with OPN (0.15-15 nM) before addition of STZ. OPN
      significantly reduced the STZ-induced NO levels in the islets through an Arg-Gly
      Asp (RGD)-dependent reduction of inducible NO synthase (iNOS) mRNA levels.
      Addition of OPN to freshly isolated mildly diabetic islets (blood glucose <300
      mg/dl) significantly improved their glucose-stimulated insulin secretion and
      reduced their NO levels. Next we investigated the regulation of OPN in beta
      cells. When STZ (5 mM) was added to the beta-cell line RINm5F it significantly
      increased OPN mRNA levels within 6 h. To distinguish between the effect of STZ
      and high glucose on OPN transcription, RINm5F cells were transfected with
      luciferase-labeled rat OPN promoter and treated with STZ (0.05-5 mM) or with
      glucose (5-25 mM). STZ induced upregulation of OPN promoter activity within 3 h,
      while high glucose induced upregulation of OPN promoter activity after 48 h. Our
      data introduce OPN as a novel islet protein that is differentially regulated by
      STZ and glucose in the islets. OPN initial upregulation after diabetes induction
      was probably due to STZ-induced toxicity, while maintenance of the high OPN
      levels might be due to hyperglycemia. The acute induction of OPN after STZ
      induced diabetes might represent an endogenous mechanism to protect the islets
      against STZ-induced cytotoxicity, partly via an RGD-dependent NO regulatory
      mechanism.

PMID- 16293772
TI  - Responses induced by arginine-vasopressin injection in the plasma concentrations
      of adrenocorticotropic hormone, cortisol, growth hormone and metabolites around
      weaning time in goats.
AB  - In order to assess the biological significance of weaning and water deprivation
      on the control of plasma concentrations of adrenocorticotropic hormone (ACTH),
      cortisol, growth hormone (GH) and metabolites in response to stimulation with
      arginine-vasopressin (AVP) and corticotropin-releasing hormone (CRH), we carried
      out three experiments in which male goats before and after weaning were
      intravenously injected with AVP or CRH alone, or in combination with each other.
      In experiment 1, 17-week-old (post-weaning) goats were intravenously injected
      with AVP or CRH alone at the doses of 0.1, 0.3 and 1.0 nmol/kg body weight (BW).
      The AVP injection significantly and dose dependently increased plasma levels of
      ACTH, cortisol, GH and metabolites, whereas the injection with CRH did not cause
      significant increases in the levels of these parameters. In experiment 2, 4-week
      old (pre-weaning) and 13-week-old (post-weaning) goats were injected with either
      AVP or CRH alone, followed by a combined injection of both secretagogues at a
      dose of 0.3 nmol/kg BW. Although the basal levels of the hormones and
      metabolites, with the exception of glucose, were greater in the 4-week-old goats,
      the hormone responses induced by stimulation with AVP were weaker than those
      induced in 13-week-old goats. Additionally, there were no responses in any
      hormone patterns to CRH stimulation in 4-week-old goats. In experiment 3, 13-week
      old goats were injected with CRH alone followed by injection with AVP for two
      consecutive days of water deprivation. The animals were subjected to withdrawal
      of up to 20% of the total blood volume and water deprivation for up to 28 h.
      However, no significant differences in plasma ACTH, cortisol or GH levels were
      observed between days 1 and 2. Based on these results, we concluded that: (1) AVP
      is a more potent stimulant than CRH in terms of its ability to induce increases
      in plasma levels of ACTH, cortisol and GH; (2) the role of AVP as a secretagogue
      of hypothalamus-pituitary-adrenal hormones is strengthened, whereas the
      ineffective role of CRH remains unaltered, by weaning; (3) acute stress such as
      massive withdrawal of blood volume and subjection to water deprivation may not be
      sufficient burdens to alter stress-related hormone levels in young goats.

PMID- 16293773
TI  - Transthyretin is not necessary for thyroid hormone metabolism in conditions of
      increased hormone demand.
AB  - Thyroid hormones circulate in blood mainly bound to plasma proteins.
      Transthyretin is the major thyroxine plasma carrier in mice. Studies in
      transthyretin-null mice revealed that the absence of transthyretin results in
      euthyroid hypothyroxinemia and normal thyroid hormone tissue distribution, with
      the exception of the choroid plexus in the brain. Therefore, transthyretin does
      not influence normal thyroid hormone homeostasis under standard laboratory
      conditions. To investigate if transthyretin has a buffer/storage role we
      challenged transthyretin-null and wild-type mice with conditions of increased
      hormone demand: (i) exposure to cold, which elicits thermogenesis, a process that
      requires thyroid hormones; and (ii) thyroidectomy, which abolishes thyroid
      hormone synthesis and secretion and induces severe hypothyroidism. Transthyretin
      null mice responded as the wild-type both to changes induced by stressful events,
      namely in body weight, food intake and thyroid hormone tissue content, and in the
      mRNA levels of genes whose expression is altered in such conditions. These
      results clearly exclude a role for transthyretin in thyroid hormone homeostasis
      even under conditions of increased hormone demand.

PMID- 16293774
TI  - Cytochrome b(5) modulation of 17{alpha} hydroxylase and 17-20 lyase (CYP17)
      activities in steroidogenesis.
AB  - CYP17 is a steroidogenic enzyme located in the zona fasciculata and zona
      reticularis of the adrenal cortex and gonad tissues and which has dual functions 
      hydroxylation and as a lyase. The first activity gives hydroxylation of
      pregnenolone and progesterone at the C(17) position to generate 17alpha
      hydroxypregnenolone and 17alpha-hydroxyprogesterone, while the second enzymic
      activity cleaves the C(17)-C(20) bond of 17alpha-hydroxypregnenolone and 17alpha
      hydroxyprogesterone to form dehydroepiandro-sterone and androstenedione
      respectively. The modulation of these two activities occurs through cytochrome
      b(5). Association of cytochrome b(5) and CYP17 is thought to be based primarily
      on electrostatic interactions in which the negatively charged residues pair up
      with positively charged residues on the proximal surface of the CYP17 molecule.
      Non-specific interactions of the hydrophobic membrane regions of cytochrome b(5)
      and CYP17 are also thought to play a crucial role in the association of these two
      haemoproteins. Although cytochrome b(5) is known to stimulate CYP activity by
      contributing the second electron in the catalytic cycle, in the case of CYP17,
      the mechanism of cleavage stimulation proceeds via an allosteric mode. It is
      hypothesised that cytochrome b(5) promotes the cleavage by aligning the iron
      oxygen complex attack onto the C(20) rather than the C(17) atom of the steroid
      substrate molecule. Thus, further understanding of the mechanism of modulation by
      cytochrome b(5) of the hydroxylase and lyase activities should shed new insights
      on developing therapeutic targets in CYP17-linked biochemical processes such as
      adrenarche, polycystic ovary syndrome and prostate cancer.

PMID- 16293775
TI  - Adrenomedullin increases cardiac sympathetic nerve activity in normal conscious
      sheep.
AB  - The sympathetic nervous system and adrenomedullin (AM) both participate in the
      regulation of cardiac and circulatory function but their interaction remains
      uncertain. We have examined the effects of AM on cardiac sympathetic nerve
      activity (CSNA) and hemodynamics and contrasted these effects with pressure
      matched nitro-prusside (NP) administration in normal conscious sheep. Compared
      with vehicle control, arterial pressure fell similarly with AM (P=0.04) and NP
      (P<0.001). Heart rate rose in response to both AM (P<0.001) and NP (P=0.002) but
      the rise with AM was significantly greater than that induced by NP (P<0.001).
      Cardiac output increased in response to AM compared with both control and NP
      (both P<0.001). CSNA burst frequency (bursts/min) were increased in response to
      both AM (P<0.001) and NP (P=0.005) with the rise in burst frequency being greater
      with AM compared with NP (P<0.001). CSNA burst area/min was also raised by both
      AM (P=0.03) and NP (P=0.002) with a trend for burst area being greater with AM
      than NP (P=0.07). CSNA burst incidence (bursts/100 beats) showed no significant
      differences between any treatment day. In conclusion, we have demonstrated that
      AM is associated with a greater increase in CSNA and heart rate for a given
      change in arterial pressure than seen with the classic balanced vasodilator NP.

PMID- 16293776
TI  - Interactions with p300 enhance transcriptional activation by the PDZ-domain
      coactivator Bridge-1.
AB  - Transcriptional coactivators are essential mediators of signal amplification in
      the regulation of gene expression in response to hormones and extracellular
      signals. We previously identified Bridge-1 (PSMD9) as a PDZ-domain coregulator
      that augments insulin gene transcription via interactions with the basic helix
      loop-helix transcription factors E12 and E47, and that increases transcriptional
      activation by the homeodomain transcription factor PDX-1. In these studies, we
      find that transcriptional activation by Bridge-1 can be regulated via
      interactions with the histone acetyltransferase and nuclear receptor coactivator
      p300. In transfection assays, transcriptional activation by Bridge-1 is increased
      by the inhibition of endogenous histone deacetylase activity with trichostatin A,
      indicating that the transcriptional activation function of Bridge-1 can be
      regulated by histone modifications. The exogenous expression of p300 enhances the
      transcriptional activation by Bridge-1 in a dose-dependent manner. In contrast,
      the sequestration of p300 by the overexpression of the adenoviral protein E1A,
      but not by an E1A mutant protein that is unable to interact with p300, suppresses
      the transcriptional activation by Bridge-1. We demonstrate that p300 and Bridge-1
      proteins interact in immunopre-cipitation and glutathione-S-transferase (GST)
      pull-down assays. Bridge-1 interacts directly with multiple regions within p300
      that encompass C/H1 or C/H2 cysteine- and histidine-rich protein interaction
      domains and the histone acetyltransferase domain. Deletion or point mutagenesis
      of the Bridge-1 PDZ domain substantially reduces transcriptional activation by
      Bridge-1 and interrupts interactions with p300. We propose that p300 interactions
      with Bridge-1 can augment the transcriptional activation of regulatory target
      genes by Bridge-1.

PMID- 16293777
TI  - A novel mechanism in control of human pigmentation by {beta}-melanocyte
      stimulating hormone and 7-tetrahydrobiopterin.
AB  - The human skin holds the full machinery for pro-opiomelanocortin processing. The
      alpha-melanocyte-stimulating hormone (alpha-MSH)/melanocortin-1-receptor cascade
      has been implicated as a major player via the cAMP signal in the control of
      melanogenesis. Only very recently the beta-endorphin/mu-opiate receptor signal
      has been added to the list of regulators of melanocyte dendricity and melanin
      formation. In this context it was reported that (6R)-l-erythro-5,6,7,8
      tetrahydrobiopterin (6BH(4)) can act as an allosteric inhibitor of tyrosinase,
      the key enzyme in melanogenesis, and this inhibition is reversible by both alpha-
      and beta-MSH. It was also shown earlier that 7BH(4), the isomer of 6BH(4), is
      twice as active in this inhibition reaction. However, as yet it is not known
      whether 7BH(4) is indeed present in loco in the melanosome. We here provide
      evidence that this isomer is present in this organelle in a concentration range
      up to 50 x 10(-6) M. Determination of beta-MSH in melanosomal extracts yielded 10
      pg/mg protein. Moreover, we demonstrate reactivation of the 7BH(4)/tyrosinase
      inhibitor complex by beta-MSH, whereas alpha-MSH failed to do so. Furthermore, we
      show intra-melanosomal l-dopa formation from dopachrome by 7BH(4) in a
      concentration range up to 134 x 10(-6) M. Based on these results, we propose a
      new receptor-independent mechanism in the control of tyrosinase/melanogenesis by
      beta-MSH and the pterin 7BH(4).

PMID- 16293778
TI  - Investigation of central versus peripheral effects of estradiol in ovariectomized
      mice.
AB  - It is generally believed that estrogens exert their bone sparing effects directly
      on the cells within the bone compartment. The aim of the present study was to
      investigate if central mechanisms might be involved in the bone sparing effect of
      estrogens. The dose-response of central (i.c.v) 17beta-estradiol (E2)
      administration was compared with that of peripheral (s.c.) administration in
      ovariectomized (ovx) mice. The dose-response curves for central and peripheral E2
      administration did not differ for any of the studied estrogen-responsive tissues,
      indicating that these effects were mainly peripheral. In addition, ovx mice were
      treated with E2 and/or the peripheral estrogen receptor antagonist ICI 182,780.
      ICI 182,780 attenuated most of the estrogenic response regarding uterus weight,
      retroperitoneal fat weight, cortical BMC and trabecular bone mineral content
      (P<0.05). These findings support the notion that the primary target tissue that
      mediates the effect of E2 on bone is peripheral and not central.

PMID- 16293780
TI  - Social support and education groups for single mothers: a randomized controlled
      trial of a community-based program.
AB  - BACKGROUND: Members of families headed by single mothers are at increased risk of
      psychosocial disadvantage and mental health problems. We assessed the effect of a
      community-based program of social support and education groups for single mothers
      of young children on maternal well-being and parenting. METHODS: We recruited 116
      single mothers of children 3 to 9 years old through community advertisements.
      Eligible mothers were randomly assigned either to participate in a 10-week
      program of group sessions (1.5 hours per week) offering social support and
      education, with a parallel children's activity group, or to receive a standard
      list of community resources and the option to participate in group sessions at
      the end of the follow-up period. Interviewers blinded to the randomization
      collected assessment data from all mothers at baseline and at 3 follow-up visits
      (immediately after the intervention and at 3 and 6 months after the
      intervention). Outcome measures were self-reported mood, self-esteem, social
      support and parenting. RESULTS: Between February 2000 and April 2003, the program
      was offered to 9 groups of single mothers. Most of the mothers in the trial
      reported high levels of financial and mental health problems. In the short term
      (after the intervention), mothers in the intervention group had improved scores
      for mood (p < 0.01, standardized effect = 0.55) and self-esteem (p < 0.05,
      standardized effect = 0.29) compared with mothers in the control group; scores
      for the other 2 measures did not differ between the groups. Growth curve analysis
      of program effects over the follow-up period showed improvement in all 4
      outcomes, with no significant difference between the intervention and control
      groups. INTERPRETATION: This community-based program of group sessions offering
      social support and education to low-income single mothers had positive short-term
      effects on mood and self-esteem but not on social support and parenting. Longer
      follow-up showed attenuation of these effects.

PMID- 16293781
TI  - Efficacy of intensive multitherapy for patients with type 2 diabetes mellitus: a
      randomized controlled trial.
AB  - BACKGROUND: National guidelines for managing diabetes set standards for care. We
      sought to determine whether a 1-year intensive multitherapy program resulted in
      greater goal attainment than usual care among patients with poorly controlled
      type 2 diabetes mellitus. METHODS: We identified patients with poorly controlled
      type 2 diabetes receiving outpatient care in the community or at our hospital.
      Patients 30-70 years of age with a hemoglobin A1c concentration of 8% or greater
      were randomly assigned to receive intensive multitherapy (n = 36) or usual care
      (n = 36). RESULTS: The average hemoglobin A1c concentration at entry was 9.1%
      (standard deviation [SD] 1%) in the intensive therapy group and 9.3% (SD 1%) in
      the usual therapy group. By 12 months, a higher proportion of patients in the
      intensive therapy group than in the control group had achieved Canadian Diabetes
      Association (CDA) goals for hemoglobin A(1c) concentrations (goal < or = 7.0%:
      35% v. 8%), diastolic blood pressure (goal < 80 mm Hg: 64% v. 37%), low-density
      lipoprotein cholesterol (LDL-C) levels (goal < 2.5 mmol/L: 53% v. 20%) and
      triglyceride levels (goal < 1.5 mmol/L: 44% v. 14%). There were no significant
      differences between the 2 groups in attaining the targets for fasting plasma
      glucose levels, systolic blood pressure or total cholesterol:high-density
      lipoprotein cholesterol ratio. None of the patients reached all CDA treatment
      goals. By 18 months, differences in goal attainment were no longer evident
      between the 2 groups, except for LDL-C levels. Quality of life, as measured by a
      specific questionnaire, increased in both groups, with a greater increase in the
      intensive therapy group (13% [SD 10%] v. 6% [SD 13%], p < 0.003). INTERPRETATION:
      Intensive multitherapy for patients with poorly controlled type 2 diabetes is
      successful in helping patients meet most of the goals set by a national diabetes
      association. However, 6 months after intensive therapy stopped and patients
      returned to usual care, the benefits had vanished.

PMID- 16293783
TI  - Stroke by cause: some common, some exotic, some controversial.

PMID- 16293782
TI  - Abnormalities in the pulmonary innate immune system in cystic fibrosis.
AB  - Pulmonary infection is the dominant clinical feature of cystic fibrosis (CF), but
      the basis for this susceptibility remains incompletely understood. One hypothesis
      is that CF airway surface liquid (ASL) is abnormal and interferes with neutrophil
      function. To study this possibility, we developed an in vitro system in which we
      collected ASL from primary cultures of normal and CF airway epithelial cells.
      Microbial killing was less efficient when bacteria were incubated with
      neutrophils in the presence of ASL from CF epithelia compared with normal ASL.
      Antimicrobial functions of human neutrophils were assessed in ASL from CF and
      normal epithelia using a combination of quantitative bacterial culture, flow
      cytometry, and microfluorescence imaging. The results of these assays of
      neutrophil function were indistinguishable in CF and normal ASL. In contrast, the
      direct bactericidal activity of ASL to Escherichia coli and to clinical isolates
      of Staphylococcus aureus and Pseudomonas aeruginosa was substantially less in CF
      than in normal ASL, even when highly diluted in media of identical ionic
      strength. Together, these observations indicate that the antimicrobial properties
      of ASL in CF are compromised in a manner independent of ionic strength of the
      ASL, and that this effect is not mediated through a direct effect of the ASL on
      phagocyte function.

PMID- 16293784
TI  - Gender differences in tPA-related arterial recanalization.

PMID- 16293785
TI  - The effect of superoxide anion on autoregulation of cerebral blood flow.
AB  - BACKGROUND AND PURPOSE: Recent studies have suggested that autoregulation of
      cerebral blood flow (CBF) is impaired after traumatic and ischemic brain injury.
      Given that the levels of superoxide anion (O2*-) are increased in these
      conditions, we postulate that O2*- contributes to the impairment of CBF
      autoregulation. METHODS: CBF was monitored with laser Doppler flowmetry during
      increases in blood pressure. RESULTS: During the control period, CBF was well
      autoregulated after the increase in mean arterial pressure (MAP) from 98+/-3 to
      140+/-6 mm Hg. The autoregulation index (AI; DeltaCBF/DeltaMAP) averaged 0.25+/
      0.02 (n=6). O2*- in the brain was then increased by subdural perfusion of
      xanthine/xanthine oxidase (different concentrations) and catalase. Low
      concentrations of O2*- decreased basal CBF by 10+/-1.6% but had no effect on
      autoregulation (AI, 0.19+/-0.02; n=6). Higher concentrations of O2*- (0.2 mmol/L
      xanthine and either 3 or 20 mU xanthine oxidase) increased basal CBF by 30+/-2%
      and 42+/-4%, respectively, and impaired autoregulation of CBF (AI, 0.55+/-0.03
      and 0.76+/-0.02; n=6). Inclusion of superoxide dismutase in the O2*(-)-generating
      system restored autoregulation (AI, 0.28+/-0.05; n=6). Neither inhibition of NO
      synthase nor the addition of deferioxamine had any effect on the ability of
      higher concentrations of O2*- to impair autoregulation of CBF (AI, 0.65+/-0.07
      and 0.72+/-0.05 respectively; n=6). O2*- also increased the activity of KCa
      channels in cerebral vascular smooth muscle cells (VSMCs; n=8). CONCLUSIONS:
      These results suggest that O2*- increases basal CBF and impairs autoregulation of
      CBF, likely through the activation of KCa channels in cerebral VSMCs.

PMID- 16293786
TI  - Carbon monoxide from heme oxygenase-2 Is a tonic regulator against NO-dependent
      vasodilatation in the adult rat cerebral microcirculation.
AB  - Although the brain generates NO and carbon monoxide (CO), it is unknown how these
      gases and their enzyme systems interact with each other to regulate
      cerebrovascular function. We examined whether CO produced by heme oxygenase (HO)
      modulates generation and action of constitutive NO in the rat pial
      microcirculation. Immunohistochemical analyses indicated that HO-2 occurred in
      neurons and arachnoid trabecular cells, where NO synthase 1 (NOS1) was
      detectable, and also in vascular endothelium-expressing NOS3, suggesting
      colocalization of CO- and NO-generating sites. Intravital microscopy using a
      closed cranial window preparation revealed that blockade of the HO activity by
      zinc protoporphyrin IX significantly dilates arterioles. This vasodilatation
      depended on local NOS activities and was abolished by CO supplementation,
      suggesting that the gas derived from HO-2 tonically regulates NO-mediated
      vasodilatory response. Bioimaging of NO by laser-confocal microfluorography of
      diaminofluorescein indicated detectable amounts of NO at the microvascular wall,
      the subdural mesothelial cells, and arachnoid trabecular cells, which express NOS
      in and around the pial microvasculature. On CO inhibition by the HO inhibitor,
      regional NO formation was augmented in these cells. Such a pattern of accelerated
      NO formation depended on NOS activities and was again attenuated by the local CO
      supplementation. Studies using cultured porcine aortic endothelial cells
      suggested that the inhibitory action of CO on NOS could result from the photo
      reversible gas binding to the prosthetic heme. Collectively, CO derived from HO-2
      appears to serve as a tonic vasoregulator antagonizing NO-mediated vasodilatation
      in the rat cerebral microcirculation.

PMID- 16293787
TI  - Phospholipase C epsilon modulates beta-adrenergic receptor-dependent cardiac
      contraction and inhibits cardiac hypertrophy.
AB  - Phospholipase C (PLC) epsilon is a recently identified enzyme regulated by a wide
      range of molecules including Ras family small GTPases, Rho A, Galpha(12/13), and
      Gbetagamma with primary sites of expression in the heart and lung. In a screen
      for human signal transduction genes altered during heart failure, we found that
      PLCepsilon mRNA is upregulated. Two murine models of cardiac hypertrophy
      confirmed upregulation of PLCepsilon protein expression or PLCepsilon RNA. To
      identify a role for PLCepsilon in cardiac function and pathology, a PLCepsilon
      deficient mouse strain was created. Echocardiography indicated PLCepsilon(-/-)
      mice had decreased cardiac function, and direct measurements of left ventricular
      contraction demonstrated that PLCepsilon(-/-) mice had a decreased contractile
      response to acute isoproterenol administration. Cardiac myocytes isolated from
      PLCepsilon(-/-) mice had decreased beta-adrenergic receptor (betaAR)-dependent
      increases in Ca2+ transient amplitudes, likely accounting for the contractile
      deficiency in vivo. This defect appears to be independent from the ability of the
      betaAR system to produce cAMP and regulation of sarcoplasmic reticulum Ca2+ pool
      size. To address the significance of these functional deficits to cardiac
      pathology, PLCepsilon(-/-) mice were subjected to a chronic isoproterenol model
      of hypertrophic stress. PLCepsilon(-/-) mice were more susceptible than wild-type
      littermates to development of hypertrophy than wild-type littermates. Together,
      these data suggest a novel PLC-dependent component of betaAR signaling in cardiac
      myocytes responsible for maintenance of maximal contractile reserve and loss of
      PLCepsilon signaling sensitizes the heart to development of hypertrophy in
      response to chronic cardiac stress.

PMID- 16293788
TI  - Nuclear targeting of Akt enhances ventricular function and myocyte contractility.
AB  - Cytoplasmic overexpression of Akt in the heart results in a myopathy
      characterized by organ and myocyte hypertrophy. Conversely, nuclear-targeted Akt
      does not lead to cardiac hypertrophy, but the cellular basis of this distinct
      heart phenotype remains to be determined. Similarly, whether nuclear-targeted Akt
      affects ventricular performance and mechanics, calcium metabolism, and electrical
      properties of myocytes is unknown. Moreover, whether the expression and state of
      phosphorylation of regulatory proteins implicated in calcium cycling and myocyte
      contractility are altered in nuclear-targeted Akt has not been established. We
      report that nuclear overexpression of Akt does not modify cardiac size and shape
      but results in an increased number of cardiomyocytes, which are smaller in
      volume. Additionally, the heart possesses enhanced systolic and diastolic
      function, which is paralleled by increased myocyte performance. Myocyte
      shortening and velocity of shortening and relengthening are increased in
      transgenic mice and are coupled with a more efficient reuptake of calcium by the
      sarcoplasmic reticulum (SR). This process increases calcium loading of the SR
      during relengthening. The enhanced SR function appears to be mediated by an
      increase in SR Ca2+-ATPase2a activity sustained by a higher degree of
      phosphorylation of phospholamban. This posttranslational modification was
      associated with an increase in phospho-protein kinase A and a decrease in protein
      phosphatase-1. Together, these observations provide a plausible biochemical
      mechanism for the potentiation of myocyte and ventricular function in Akt
      transgenic mice. Therefore, nuclear-targeted Akt in myocytes may have important
      implications for the diseased heart.

PMID- 16293789
TI  - Excitation-contraction coupling in Na+-Ca2+ exchanger knockout mice: reduced
      transsarcolemmal Ca2+ flux.
AB  - Cardiac-specific Na+-Ca2+ exchanger (NCX) knockout (KO) mice surprisingly survive
      into adulthood without compensatory changes in protein expression levels. To
      determine how cardiac function is maintained in the absence of NCX, we
      investigated membrane currents, intracellular Ca2+, and action potentials (APs)
      in whole cell patch-clamped myocytes from wild-type (WT) and NCX knockout mice.
      There was no difference in resting Ca2+ or sarcoplasmic reticular Ca2+ load
      between KO and WT. During prolonged caffeine exposure, the decrease of the Ca2+
      transient was drastically slowed in KO versus WT myocytes, indicating that no
      alternative Ca2+-extrusion mechanism is upregulated to compensate for the absence
      of NCX. Peak L-type Ca2+ current (ICa) was reduced by 62% in KO myocytes compared
      with WT. Nevertheless, the corresponding Ca2+ transients were similar, implying
      an increase in the gain of excitation-contraction coupling in KO cells. APs
      recorded from KO cells repolarized more rapidly than in WT. In WT myocytes,
      applying a KO AP waveform voltage clamp reduced Ca2+ influx via ICa by 59%
      compared with WT AP waveform clamps. Again, the corresponding Ca2+ transients
      remained similar. Our findings indicate that NCX KO myocytes limit Ca2+ influx to
      &20% of that in WT by reducing ICa and by abbreviating the AP. Contractility is
      maintained by an increase in the gain of excitation-contraction coupling
      resulting from both a more rapid repolarization of the AP and an as yet
      unidentified AP-independent mechanism.

PMID- 16293790
TI  - Targeted deletion of Kv4.2 eliminates I(to,f) and results in electrical and
      molecular remodeling, with no evidence of ventricular hypertrophy or myocardial
      dysfunction.
AB  - Previous studies have demonstrated a role for voltage-gated K+ (Kv) channel alpha
      subunits of the Kv4 subfamily in the generation of rapidly
      inactivating/recovering cardiac transient outward K+ current, I(to,f), channels.
      Biochemical studies suggest that mouse ventricular I(to,f) channels reflect the
      heteromeric assembly of Kv4.2 and Kv4.3 with the accessory subunits, KChIP2 and
      Kvbeta1, and that Kv4.2 is the primary determinant of regional differences in
      (mouse ventricular) I(to,f) densities. Interestingly, the phenotypic consequences
      of manipulating I(to,f) expression in different mouse models are distinct. In the
      experiments here, the effects of the targeted deletion of Kv4.2 (Kv4.2(-/-)) were
      examined. Unexpectedly, voltage-clamp recordings from Kv4.2(-/-) ventricular
      myocytes revealed that I(to,f) is eliminated. In addition, the slow transient
      outward K+ current, I(to,s), and the Kv1.4 protein (which encodes I(to,s)) are
      upregulated in Kv4.2(-/-) ventricles. Although Kv4.3 mRNA/protein expression is
      not measurably affected, KChIP2 expression is markedly reduced in Kv4.2(-/-)
      ventricles. Similar to Kv4.3, expression of Kvbeta1, as well as Kv1.5 and Kv2.1,
      is similar in wild-type and Kv4.2(-/-) ventricles. In addition, and in marked
      contrast to previous findings in mice expressing a truncated Kv4.2 transgene, the
      elimination I(to,f) in Kv4.2(-/-) mice does not result in ventricular
      hypertrophy. Taken together, these findings demonstrate not only an essential
      role for Kv4.2 in the generation of mouse ventricular I(to,f) channels but also
      that the loss of I(to,f) per se does not have overt pathophysiological
      consequences.

PMID- 16293791
TI  - Protective effect of the KCNMB1 E65K genetic polymorphism against diastolic
      hypertension in aging women and its relevance to cardiovascular risk.
AB  - The E65K polymorphism in the beta1-subunit of the large-conductance, Ca2+
      dependent K+ (BK) channel, a key element in the control of arterial tone, has
      recently been associated with low prevalence of diastolic hypertension. We now
      report the modulatory effect of sex and age on the association of the E65K
      polymorphism with low prevalence of diastolic hypertension and the protective
      role of E65K polymorphism against cardiovascular disease. We analyzed the
      genotype frequency of the E65K polymorphism in 3924 participants selected
      randomly in two cross-sectional studies. A five-year follow-up of the cohort was
      performed to determine whether cardiovascular events had occurred since
      inclusion. Estrogen modulation of wild-type and mutant ion channel activity was
      assessed after heterologous expression and electrophysiological studies.
      Multivariate regression analyses showed that increasing age upmodulates the
      protective effect of the K allele against moderate-to-severe diastolic
      hypertension in the overall group of participants (odds ratio [OR], 0.35;
      P=0.006). The results remained significant when analyses were restricted to women
      (OR, 0.18; P=0.02) but not men (OR, 0.46; P=0.09). This effect was independent of
      the reported acute modulation of BK channels by estrogen. A five-year follow-up
      study also demonstrated a reduced age- and sex-adjusted hazard ratio of 0.11, 95%
      CI, 0.01 to 0.79 of K-carriers for "combined cardiovascular disease" (myocardial
      infarction and stroke) compared with EE homozygotes. Our study provides the first
      genetic evidence for the different impact of the BK channel in the control of
      human blood pressure in men and women, with particular relevance in aging women,
      and highlights the E65K polymorphism as one of the strongest genetic factors
      associated thus far to protection against myocardial infarction and stroke.

PMID- 16293792
TI  - Role of cAMP response element binding protein in cardiovascular remodeling: good,
      bad, or both?
AB  - The cAMP response element binding protein (CREB) is a ubiquitously expressed
      nuclear transcription factor that is activated by various extracellular stimuli.
      CREB is known to regulate the expression of genes important to cell
      proliferation, differentiation, adaptation, and survival in many cell types. Loss
      of CREB function by transgenic overexpression of dominant negative CREB or
      targeted deletion of the CREB gene revealed that CREB is involved in the
      differentiation of T lymphocytes, production of growth hormone, and the long-term
      potentiation of neuronal memory. The role of CREB in cardiovascular system is
      incompletely characterized and several controversies remain. A growing body of
      recent evidence, however, has suggested that CREB plays an important role in the
      cardiovascular remodeling process, including inflammation, cell migration, and
      apoptosis. Thus, CREB may be a possible target for the treatment of
      cardiovascular diseases such as atherosclerosis, restenosis, and reperfusion
      injury.

PMID- 16293793
TI  - Aspirin has a gender-dependent impact on antiinflammatory 15-epi-lipoxin A4
      formation: a randomized human trial.
AB  - OBJECTIVE: Aspirin blocks thromboxane production that contributes to its well
      appreciated antiplatelet action. Aspirin also initiates the biosynthesis of novel
      antiinflammatory mediators from arachidonic acid, namely aspirin-triggered 15-epi
      lipoxin A4. We recently conducted a double-blinded clinical trial with healthy
      subjects in whom low-dose aspirin (81 mg daily) significantly increased aspirin
      triggered 15-epi-lipoxin A4 and concomitantly inhibited thromboxane. Here, we
      assessed whether plasma aspirin-triggered 15-epi-lipoxin A4 was age or gender
      dependent in subjects taking low-dose aspirin. METHODS AND RESULTS: A total of
      128 subjects were allocated to: placebo, 81, 325, or 650 mg daily aspirin for an
      8-week period. Plasma thromboxane B2 and aspirin-triggered 15-epi-lipoxin A4 were
      assessed from blood collected at baseline and the conclusion of the trial. We
      then performed a post-trial analysis in the group receiving low-dose aspirin. In
      female subjects, we found a positive correlation between age and aspirin
      triggered 15-epi-lipoxin A4(increase of 0.37 ng/mL per decade), and a negative
      correlation was observed in men (decrease of 0.29 ng/mL per decade). These trends
      were significantly different from each other (P=0.045). CONCLUSIONS: Low-dose
      aspirin has a gender-specific impact on aspirin-triggered 15-epi-lipoxin A4
      production, which may contribute to the gender-dependent clinical benefits of
      aspirin. Also, they may provide a molecular rationale for low-dose aspirin
      therapies in elderly women to reduce inflammation-related disorders.

PMID- 16293794
TI  - Coronary artery superoxide production and nox isoform expression in human
      coronary artery disease.
AB  - BACKGROUND: Oxidative stress plays important role in the pathogenesis of
      atherosclerosis and coronary artery disease (CAD). We aimed to determine the
      sources and selected molecular mechanisms of oxidative stress in CAD. METHODS AND
      RESULTS: We examined basal and NAD(P)H oxidase-mediated superoxide (O2*-)
      production using lucigenin chemiluminescence, ferricytochrome c and
      dihydroethidium fluorescence in human coronary arteries from 19 CAD and 17 non
      CAD patients undergoing heart transplantation. NAD(P)H oxidase subunits and
      xanthine oxidase expression were measured. Superoxide production was greater in
      coronary arteries from patients with CAD, even in vessels without overt
      atherosclerotic plaques, and was doubled within branching points of coronary
      arteries. Studies using pharmacological inhibitors and specific substrates showed
      that NAD(P)H oxidases (60%) and xanthine oxidase (25%) are primary sources of O2*
      in CAD. Losartan significantly inhibited superoxide production in coronary
      arteries. NAD(P)H oxidase activity and protein levels of the NADPH oxidase
      subunits p22phox, p67phox, and p47phox were significantly increased in CAD, as
      were mRNA levels for p22phox and nox2, and no NAD(P)H oxidase subunit mRNA levels
      correlated with NAD(P)H oxidase activity in vessels from individual patients.
      Activity and protein expression of xanthine oxidase were increased in CAD,
      whereas xanthine dehydrogenase levels were not changed. CONCLUSIONS: Increased
      expression and activity of NAD(P)H oxidase subunits and xanthine oxidase, in part
      mediated through angiotensin II and PKC-dependent pathways, are important
      mechanisms underlying increased oxidative stress in human coronary artery
      disease.

PMID- 16293795
TI  - Expression profiling identifies smooth muscle cell diversity within human intima
      and plaque fibrous cap: loss of RGS5 distinguishes the cap.
AB  - BACKGROUND: The fibrous cap of the atherosclerotic lesion is believed to be
      critical to stability because disruption of the cap is the final event leading to
      plaque rupture. We have, therefore, used expression arrays to define the
      phenotype of the cap and other plaque components. METHODS AND RESULTS: To
      identify unique expression programs able to distinguish the smooth muscle of the
      cap from other plaque smooth muscle cells, RNA profiles were determined in human
      carotid artery media, nonatherosclerotic adjacent intima, fibrous cap of advanced
      atherosclerotic plaques, and whole advanced plaque with cDNA arrays covering
      21,000 or 26,000 Unigene clusters. The molecular signature of each tissue was
      dominated by a core gene-set with differential expression of <1% of clusters
      assayed. CONCLUSIONS: Both intima and cap expressed novel genes not previously
      associated with SMC pathology. If the cap is derived from a unique subpopulation,
      this pattern is the signature of that particular set of cells. The loss of RGS5
      in the fibrous cap is of particular interest because of its role in vessel
      development and physiology.

PMID- 16293796
TI  - Transcriptional profiles of valvular and vascular endothelial cells reveal
      phenotypic differences: influence of shear stress.
AB  - OBJECTIVE: The similarities between valvular and vascular lesions suggest
      pathological initiation mediated through endothelium, but the role of
      hemodynamics in valvular endothelial biology is poorly understood. METHODS AND
      RESULTS: Monolayers of porcine aortic endothelial cells (PAECs) or porcine aortic
      valve endothelial cells (PAVECs) were exposed to 20 dyne/cm2 steady laminar shear
      stress for 48 hours, with static cultures serving as controls. Multiple
      microarray comparisons were made using RNA from sheared and control batches of
      both cell types. More than 400 genes were significantly differentially expressed
      in each comparison group. The resulting profiles were validated at the
      transcription and protein level and expression patterns confirmed in vivo by
      immunohistochemistry. PAVECs were found to be less intrinsically inflammatory
      than PAECs, but both cell types expressed similar antioxidant and
      antiinflammatory genes in response to shear stress. PAVECs expressed more genes
      associated with chondrogenesis, whereas PAECs expressed osteogenic genes, and
      shear stress had a protective effect against calcification. CONCLUSIONS:
      Transcriptional differences between PAVECs and PAECs highlight the valvular
      endothelial cell as a distinct organ system and suggest more attention needs to
      be given to valvular cells to further our understanding of similarities and
      differences between valvular and vascular pathology.

PMID- 16293797
TI  - Correlation of vasa vasorum neovascularization and plaque progression in aortas
      of apolipoprotein E(-/-)/low-density lipoprotein(-/-) double knockout mice.
AB  - OBJECTIVE: We hypothesized that apolipoprotein E (apoE)(-/-)/low-density
      lipoprotein (LDL)(-/-) double knockout mice might develop vasa vasorum (VV) in
      association with advanced lesion formation. METHODS AND RESULTS: Aortas from
      apoE(-/-)/LDL(-/-) mice aged 16, 18, 20, or 80 weeks were infused in situ with
      Microfil, harvested, and scanned with micro-computed tomography (CT). We
      characterized plaque volume and CT "density" as well as VV luminal volume along
      the aorta using Analyze 6.0 software. Results were complemented by a detailed
      histological plaque classification according to American Heart Association
      guidelines. From 16 to 80 weeks, plaque volume and VV opacified lumen volume
      increased with age (P<0.001). The 3-dimensional micro-CT images of arterial and
      venous VV trees allowed perfusion territories to be delineated. The spatial
      location and magnitude of VV density and adventitial inflammation were strongly
      correlated in advanced atherosclerotic lesions (r=0.91) and identified as an
      independent correlate to advanced lesions. At age 80 weeks, VV luminal volume was
      increased 20-fold compared with animals at age 16 weeks (P<0.001). Micro-CT
      showed that adventitial VV communicate with intraplaque microvessels.
      CONCLUSIONS: Our results show that apoE(-/-)/LDL(-/-) double knockout mice
      develop VV and advanced atheromas along the aorta. Lesion volume was closely
      associated with amount of neovascularization in advanced atheromas.

PMID- 16293798
TI  - Endothelial nitric oxide synthase: host defense enzyme of the endothelium?
AB  - This article explores the physiology of superoxide generation by endothelial
      nitric oxide synthase (eNOS), the so-called "uncoupled" state of the enzyme. The
      fact that this alternative chemistry of the eNOS enzyme is evolutionary strongly
      conserved, suggests that it may play a physiological role. It is proposed that
      this uncoupled state may contribute to defense against infections. As the switch
      from NO production to reactive oxygen species by eNOS is also the final common
      pathway in atherogenesis, the uncoupling of eNOS further builds on the hypothesis
      that atherogenesis is driven by cellular mechanisms that originally serve host
      defense. The central role of uncoupled eNOS in redox signaling in the endothelium
      may open up new avenues for therapy to prevent atherosclerosis.

PMID- 16293799
TI  - Interleukin-18 and macrophage migration inhibitory factor are associated with
      increased carotid intima-media thickening.
AB  - OBJECTIVE: Carotid intima-media thickening (IMT) is a form of vascular remodeling
      that has a strong genetic component. Recently, we discovered that in response to
      decreased carotid blood flow SJL mice developed the largest intima among 5 inbred
      strains. Because the SJL strain is prone to autoimmune diseases, we hypothesized
      that inflammation contributed to IMT in SJL mice. METHODS AND RESULTS: We
      compared vascular remodeling (induced by 2 weeks of low flow) in 2 strains with
      small IMT (C3H/HeJ and C3HeB/FeJ) versus 2 strains with large IMT (FVB/NJ and
      SJL/J). Quantitative immunohistochemistry showed a dramatic increase in
      inflammatory cells per intima area in SJL compared with other strains. Microarray
      profiling of inflammatory gene mRNAs from carotids showed significant increases
      in interleukin (IL)-18 and Mif gene expression in SJL compared with C3HeB/FeJ
      mice. Increased expression of these genes was confirmed by quantitative reverse
      transcription polymerase chain reaction and immunohistochemistry. Furthermore,
      greater cell proliferation in the intima of SJL accounted for increased intima
      media thickening, whereas a higher level of apoptosis and a lower level of
      proliferation were observed in C3HeB/FeJ mice. CONCLUSIONS: The present study
      indicates that increased expression of Mif and IL-18 cytokines is associated with
      intima-media thickening in SJL mice, likely by stimulating inflammation and
      proliferation.

PMID- 16293800
TI  - Novel action of indoleamine 2,3-dioxygenase attenuating acute lung allograft
      injury.
AB  - RATIONALE: Lung allografts are prone to reperfusion injury and acute rejection,
      which, in addition to infiltrating lymphocytes, are accompanied by neutrophil
      infiltration and neutrophil-associated oxidative stress. Indoleamine 2,3
      dioxygenase (IDO) is a unique cytosolic enzyme that possesses T-cell-suppressive
      and antioxidant properties. OBJECTIVES: The purpose of this study was to
      determine if genetic up-regulation of IDO could ameliorate acute lung allograft
      injury. METHODS: Lung orthotopic transplants were performed using Lewis donors
      and Sprague-Dawley rat recipients (allografts) or the same strain (isografts).
      Plasmid-encoding human IDO was delivered to donor lungs in vivo using a nonviral
      gene-transfer vector, polyethylenimine. Transplanted lungs were evaluated at 6 d
      post-transplantation based on pulmonary function, histology, inflammatory
      responses, and their associated oxidative stress. Basic biology of the IDO
      overexpressing lung cells was evaluated in vitro in response to external oxidant.
      MEASUREMENTS AND MAIN RESULTS: This gene delivery method led to uniform transgene
      expression in lung tissue distributed in airway, alveolar epithelial, and
      endothelial cells. IDO overexpression in lung allografts resulted in a
      significant protective effect with improvement in functional properties (peak
      airway pressure and oxygenation) and histologic appearance. Although IDO was able
      to block local T-cell responses, it failed to abrogate neutrophilic infiltration
      and the inflammation-associated oxidative stress. IDO-enhanced lung cells were
      resistance to oxidant-induced necrosis and apoptosis by limiting intracellular
      reactive oxygen species formation. CONCLUSIONS: These results demonstrate that
      IDO prevents acute lung allograft injury through augmenting the local antioxidant
      defense system and inhibiting alloreactive T-cell responses.

PMID- 16293801
TI  - Influence of leukotriene pathway polymorphisms on response to montelukast in
      asthma.
AB  - RATIONALE: Interpatient variability in montelukast response may be related to
      variation in leukotriene pathway candidate genes. OBJECTIVE: To determine
      associations between polymorphisms in leukotriene pathway candidate genes with
      outcomes in patients with asthma receiving montelukast for 6 mo who participated
      in a clinical trial. METHODS: Polymorphisms were typed using Sequenom matrix
      assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass array
      spectrometry and published methods; haplotypes were imputed using single
      nucleotide polymorphism-expectation maximization (SNP-EM). Analysis of variance
      and logistic regression models were used to test for changes in outcomes by
      genotype. In addition, chi(2) and likelihood ratio tests were used to test for
      differences between groups. Case-control comparisons were analyzed using the SNP
      EM Omnibus likelihood ratio test. MEASUREMENTS: Outcomes were asthma exacerbation
      rate and changes in FEV(1) compared with baseline. RESULTS: DNA was collected
      from 252 participants: 69% were white, 26% were African American. Twenty-eight
      SNPs in the ALOX5, LTA4H, LTC4S, MRP1, and cysLT1R genes, and an ALOX5 repeat
      polymorphism were successfully typed. There were racial disparities in allele
      frequencies in 17 SNPs and in the repeat polymorphism. Association analyses were
      performed in 61 whites. Associations were found between genotypes of SNPs in the
      ALOX5 (rs2115819) and MRP1 (rs119774) genes and changes in FEV(1) (p < 0.05), and
      between two SNPs in LTC4S (rs730012) and in LTA4H (rs2660845) genes for
      exacerbation rates. Mutant ALOX5 repeat polymorphism was associated with
      decreased exacerbation rates. There was strong linkage disequilibrium between
      ALOX5 SNPs. Associations between ALOX5 haplotypes and risk of exacerbations were
      found. CONCLUSIONS: Genetic variation in leukotriene pathway candidate genes
      contributes to variability in montelukast response.

PMID- 16293802
TI  - Air pollution and markers of inflammation and coagulation in patients with
      coronary heart disease.
AB  - RATIONALE: Ambient air pollution has been shown to be associated with
      cardiovascular morbidity and mortality. OBJECTIVES: A prospective panel study was
      conducted to study the early physiologic reactions characterized by blood
      biomarkers of inflammation, endothelial dysfunction, and coagulation in response
      to daily changes in air pollution in Erfurt, Germany. METHODS: Blood parameters
      were repeatedly measured in 57 male patients with coronary heart disease during
      the winter of 2000/2001. Fixed-effects linear and logistic regression models were
      applied, adjusting for trend, weekday, and meteorologic parameters. MEASUREMENTS:
      Hourly data on ultrafine particles (UFPs; number concentration of particles from
      0.01 to 0.1 microm), mass concentration of particles less than 10 (PM(10)) and
      2.5 microm in diameter, elemental and organic carbon, gaseous pollutants, and
      meteorologic data were collected at central monitoring sites. MAIN RESULTS:
      Increased levels of C-reactive protein above the 90th percentile were observed
      for an increase in air pollution concentrations of one interquartile range. The
      effect was strongest for accumulation mode particles, with a delay of 2 d (odds
      ratio [OR], 3.2; confidence interval [CI], 1.7, 6.0). Results were consistent for
      UFPs and PM(10), which also showed a 2-d delayed response (OR, 2.3; CI, 1.3, 3.8;
      and OR, 2.2; CI, 1.2, 3.8, respectively). However, not all of the blood markers
      of endothelial dysfunction and coagulation increased consistently in association
      with air pollutants. CONCLUSION: These results suggest that inflammation as well
      as parts of the coagulation pathway may contribute to the association between
      particulate air pollution and coronary events.

PMID- 16293803
TI  - Complement C3a and C4a increased in plasma of patients with aspirin-induced
      asthma.
AB  - RATIONALE: Aspirin-induced asthma (AIA) is a distinct clinical syndrome that
      affects up to 10% of adults with asthma. Although eicosanoid metabolites appear
      to play an important role in AIA, the exact pathogenic mechanism for the syndrome
      remains obscure. In addition, the proposed mechanism fails to explain why aspirin
      does not cause bronchoconstriction in all individuals. OBJECTIVES: We aimed to
      identify proteins that were differentially expressed in between AIA and aspirin
      tolerant asthma (ATA) plasma. METHODS AND MAIN RESULTS: By using a proteomics
      approach, six proteins were found to be differentially expressed in plasma
      between patients with AIA and patients with ATA at baseline, and eight proteins
      were significantly up- or down-regulated after aspirin challenge in patients with
      AIA. These proteins, which were identified by matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, can be
      classified into four groups: complement components, apolipoproteins, modified
      albumin, and unknown proteins. Among them, the complement component levels in
      plasma were validated by using ELISA. Plasma concentrations of C3a and C4a were
      higher in patients with AIA (n = 30) than in patients with ATA (n = 24). After
      the aspirin challenge, C3 decreased in both patients with AIA and those with ATA,
      but the C3a concentration increased in the AIA patient group (p = 0.019).
      Moreover, C3a and C4a levels and the ratios of C3a/C3 and C4a/C4 were correlated
      with the changes of FEV(1) values after aspirin challenge. CONCLUSIONS: Aspirin
      intolerance may be related to alterations in the levels of complements, as well
      as those of lipoprotein and other proteins.

PMID- 16293804
TI  - Prediction of prognosis for acute respiratory distress syndrome with thin-section
      CT: validation in 44 cases.
AB  - PURPOSE: To retrospectively evaluate whether the thin-section computed
      tomographic (CT) appearance has prognostic value for prediction of mortality,
      number of ventilator-free days (ie, days without mechanical ventilation), and 28
      day risk of barotrauma in patients with a clinically early stage of acute
      respiratory distress syndrome (ARDS) from diverse causes. MATERIALS AND METHODS:
      Institutional review board approval and informed consent were obtained. Two
      independent observers who were blinded to patient outcomes retrospectively
      evaluated the thin-section CT scans obtained within 7 days after clinical ARDS
      onset in 26 survivors and 18 nonsurvivors. Of 44 patients, there were 37 men and
      seven women (mean age +/- standard deviation, 61.8 years +/- 15.6). CT findings
      were graded on a scale of 1-6 that corresponded with consecutive pathologic
      phases: score of 1, normal attenuation; score of 2, ground-glass attenuation;
      score of 3, consolidation; score of 4, ground-glass attenuation associated with
      traction bronchiolectasis or bronchiectasis; score of 5, consolidation associated
      with traction bronchiolectasis or bronchiectasis; and score of 6, honeycombing.
      An overall CT score was obtained by adding the six averaged scores (three zones
      in each lung). Multivariate regression analysis was used to assess the
      independent predictive value of the CT score. RESULTS: The area of increased
      attenuation associated with traction bronchiolectasis or bronchiectasis (P =
      .002), as well as the overall CT score (P = .002), was smaller in survivors than
      in nonsurvivors. Results of multivariate regression analysis revealed that CT
      score was independently associated with mortality (P = .006). A CT score of less
      than 230 enabled prediction of survival with 73% sensitivity and 75% specificity
      and was associated with both a greater number of ventilator-free days (P = .018)
      and a lower incidence of barotrauma (P = .013) within 28 days after ARDS onset.
      CONCLUSION: Extensive thin-section CT abnormalities indicative of
      fibroproliferative changes were independently predictive of poor prognosis in
      patients with a clinically early stage of ARDS.

PMID- 16293805
TI  - Osteoid osteoma in an ex vivo animal model: temperature changes in surrounding
      soft tissue during CT-guided radiofrequency ablation.
AB  - PURPOSE: To assess temperature changes in the soft tissue surrounding bone during
      radiofrequency (RF) ablation of osteoid osteoma in an ex vivo animal model.
      MATERIALS AND METHODS: Intracortical cavities were created in fresh bovine long
      bone specimens obtained from a slaughterhouse as models for osteoid osteoma.
      Three groups of three specimens each were defined according to the thickness (1,
      3, and 5 mm) of the cortical bone lamella separating the nidus from the
      periosteum. Three thermocouples were applied to the soft tissue surrounding the
      bone in defined distances (0, 5, and 10 mm) from the periosteum. Before RF
      ablation, the thickness of the cortical bone lamella was documented at computed
      tomography. Specimens were heated in a 37 degrees C basin. As soon as the
      measured temperature in the cavity of the specimen reached 35 degrees C, RF
      ablation was performed for 400 seconds, with a target temperature of 95 degrees
      C. During RF ablation, continuous measurements were performed simultaneously with
      digital thermometers. No simulation of vessel perfusion was used. The effect of
      the thickness of residual osseous lamella and the effect of the distance between
      the thermocouple and the periosteum were tested with an analysis of variance.
      Post hoc Bonferroni tests were performed. RESULTS: Mean maximum temperatures of
      69.1 degrees, 51.3 degrees, and 42.5 degrees C for 1-mm lamella; 59.2 degrees,
      46.5 degrees, and 41.1 degrees C for 3-mm lamella; and 50.6 degrees, 44.8
      degrees, and 40.0 degrees C for 5-mm lamella were measured 0, 5, and 10 mm,
      respectively, from the periosteum. Significant temperature differences were shown
      with analysis of variance and post hoc tests for the three groups of bone lamella
      thickness and distance (P < .001). CONCLUSION: In the model of osteoid osteoma,
      the surrounding temperature (soft tissue) during RF ablation was shown to depend
      on the thickness of the cortical bone lamella and the distance from the
      periosteum.

PMID- 16293806
TI  - Evaluation of bowel distention and bowel wall appearance by using neutral oral
      contrast agent for multi-detector row CT.
AB  - PURPOSE: To prospectively evaluate the performance of an orally administered 0.1%
      barium suspension, Volumen, as a bowel-marking agent for multi-detector row
      computed tomography (CT). MATERIALS AND METHODS: This HIPAA-compliant study was
      approved by the Institutional Review Board and conformed to the institutional
      standards for research funded by a commercial sponsor. A total of 60 patients (33
      women, 27 men; average age, 58.2 years) who were referred for multi-detector row
      CT of the pancreas were randomized into two groups. Prior to examination, group 1
      consumed 1200 mL of Volumen over a 30-minute period and group 2 consumed 1200 mL
      of a solution containing three parts water and one part methylcellulose over a 30
      minute period. Results were independently reviewed by two radiologists who were
      unaware of the contrast agent used. The degree of distention and the
      visualization of mural detail were qualitatively scored on a five-point scale.
      Differences were evaluated by using the Mann-Whitney test at a confidence level
      of 95%. RESULTS: There was significantly better distention in the stomach (P =
      .013), duodenum (P = .006), jejunum (P = .029), and ileum (P = .014) [corrected]
      in group 1 compared with group 2. Significant distention was also evident by
      comparing the products of the widest cross-sectional diameters in duodenum (P =
      .143), jejunum (P < .001), and ileum (P < .001). Group 1 also demonstrated
      significantly better visualization of mural features in the duodenum (P = .003),
      jejunum (P = .024), and ileum (P = .01) and a trend toward better visualization
      of mural features in the stomach (P = .092). CONCLUSION: Oral administration of
      Volumen provided excellent distention and excellent visualization of mural
      features in the gastrointestinal tract.

PMID- 16293807
TI  - Small-bowel obstruction: coronal reformations from isotropic voxels at 16-section
      multi-detector row CT.
AB  - PURPOSE: To retrospectively assess the added value of coronal reformations of the
      abdomen and pelvis from isotropic voxels by using 16-section multi-detector row
      computed tomography (CT) for the diagnosis of small-bowel obstruction (SBO).
      MATERIALS AND METHODS: This HIPAA-compliant study was approved by the
      institutional review board of this medical center with a waiver of informed
      consent. One hundred consecutive patients (40 men and 60 women; mean age, 55
      years) suspected of having SBO and abdominal pain underwent 16-section multi
      detector row CT with coronal reformations. Twenty-nine patients had a final
      diagnosis of SBO, and 71 patients did not. Three independent readers blinded to
      the diagnosis interpreted the CT scout scan, then transverse scans alone, and
      then transverse plus coronal scans for the presence of SBO and abnormal wall
      enhancement. Confidence was scored with a 1-5 scale (1 = absent, 5 = present).
      RESULTS: Mean sensitivity and specificity of CT scout alone, transverse CT alone,
      and transverse plus coronal CT for the diagnosis of SBO were 88% and 86%, 87% and
      87%, and 87% and 90%, respectively (not significant). In patients without SBO,
      transverse plus coronal CT enhanced confidence in the exclusion of SBO (P = .01).
      In patients with SBO, transverse plus coronal CT enhanced confidence in the
      diagnosis of SBO and identification of abnormal wall enhancement (P = .01).
      CONCLUSION: Transverse 16-section multi-detector row CT data sets are an
      excellent test for the diagnosis of SBO, while the addition of coronal
      reformations obtained from these isotropic data sets adds confidence to the
      diagnosis and exclusion of SBO.

PMID- 16293808
TI  - Incidental word learning in a hearing child of deaf adults.
AB  - It is unclear how children develop the ability to learn words incidentally (i.e.,
      without direct instruction or numerous exposures). This investigation examined
      the early achievement of this skill by longitudinally tracking the expressive
      vocabulary and incidental word-learning capacities of a hearing child of Deaf
      adults who was natively learning American Sign Language (ASL) and spoken English.
      Despite receiving only 20% of language input in spoken English, the child's
      expressive vocabularies at 16 and 20 months of age, in each language, were
      similar to those of monolingual age-matched peers. At 16 months of age, the child
      showed signs of greater proficiency in the incidental learning of novel ASL signs
      than she did for spoken English words. At 20 months of age, the child was skilled
      at incidental word learning in both languages. These results support the
      methodology as it applies to examining theoretical models of incidental word
      learning. They also suggest that bilingual children can achieve typical
      vocabulary levels (even with minimal input in one of the languages) and that the
      development of incidental word learning follows a similar trajectory in ASL and
      spoken English.

PMID- 16293809
TI  - Traditional ethics and new sensitivities.

PMID- 16293810
TI  - Financial capacity in persons with schizophrenia and serious mental illness:
      clinical and research ethics aspects.
AB  - In contrast with issues of consent capacity, financial capacity has received
      surprisingly little clinical or ethical attention in the psychiatric literature.
      Issues of financial capacity emerge frequently regarding clients with serious
      mental illness (SMI), and their resolution has practical and ethical significance
      for clients, their families, and mental health professionals. These issues
      include whether a client has sufficient financial skills and judgment to live
      independently, whether a client requires a representative payee, and what goals
      for community reintegration should be established with a client. Similar to
      informed consent, issues of financial capacity raise ethical challenges for
      clinicians, caseworkers, and agencies. The present article addresses clinical and
      research ethics questions related to financial capacity in clients with
      schizophrenia and SMI. Clinical questions concern evaluation of financial
      capacity in clients with SMI, whether to seek assignment of a mandatory
      representative payee, whether to leverage treatment compliance through a
      representative payee arrangement, and whether a mental health professional should
      also serve as a client's representative payee. The research ethics question
      addresses implications of providing financial compensation for research
      participation to individuals with SMI and limited financial capacity and means.
      The ultimate goal of this article is to focus clinical and ethical attention on a
      neglected decisional capacity in SMI that is of fundamental importance for
      clients, families, clinicians, and researchers.

PMID- 16293811
TI  - Metabolic syndrome.

PMID- 16293812
TI  - Extended prescribing by UK nurses and pharmacists.

PMID- 16293813
TI  - European developments in labelling allergenic foods.

PMID- 16293814
TI  - Primary care trusts: do they have a future?

PMID- 16293815
TI  - The private health sector in India.

PMID- 16293818
TI  - Lords back bill to legalise assisted suicide.

PMID- 16293819
TI  - Dignitas is investigated for helping healthy woman to die.

PMID- 16293820
TI  - Woman fights for parents' right to know abortion advice to under 16s.

PMID- 16293821
TI  - Watchdog finds that NHS is failing stroke patients.

PMID- 16293822
TI  - Austrian woman sues doctor and hospital for sterilising her without consent.

PMID- 16293823
TI  - GMC hears charge that doctor ended a patient's life prematurely.

PMID- 16293828
TI  - EU is urged to reduce injuries to children.

PMID- 16293833
TI  - Rebuilding Afghanistan's health service is hampered by insecurity and lack of
      funds.

PMID- 16293835
TI  - Industry steps up efforts to develop avian flu vaccine.

PMID- 16293836
TI  - WHO agrees global action plan to control avian flu.

PMID- 16293839
TI  - Obesity and type 2 diabetes in children, 1996-7 to 2003-4.

PMID- 16293840
TI  - Risk of cervical and other cancers after treatment of cervical intraepithelial
      neoplasia: retrospective cohort study.
AB  - OBJECTIVE: To study the long term risk of cervical and other cancers after
      treatment for cervical intraepithelial neoplasia. DESIGN: Retrospective cohort
      study. SETTING: University Hospital, Helsinki, Finland. PARTICIPANTS: 7564 women
      treated for cervical intraepithelial neoplasia during 1974 and 2001 and followed
      up through the Finnish cancer registry until 2003. MAIN OUTCOME MEASURES:
      Standardised incidence ratio for cervical cancer and other cancers. RESULTS:
      During follow-up 22 cases of invasive cervical cancer occurred in women treated
      for cervical intraepithelial neoplasia (standardised incidence ratio 2.8, 95%
      confidence interval 1.7 to 4.2). The highest risk was during the second decade
      (10 cases observed: 3.1, 1.5 to 5.7). The standardised incidence ratio for
      cervical intraepithelial cancer type 1 was 3.1 (1.4 to 6.2) and for type 2 was
      3.7 (0.9 to 10.7). CONCLUSIONS: The risk of cervical cancer in the first 20 years
      after treatment for cervical intraepithelial neoplasia is higher than in the
      average population. The risk of smoking related cancers is also increased.

PMID- 16293841
TI  - The parents' journey: continuing a pregnancy after a diagnosis of Patau's
      syndrome.

PMID- 16293842
TI  - Improving services with informatics tools.

PMID- 16293843
TI  - Challenges of private provision in the NHS.

PMID- 16293844
TI  - Competition in general practice.

PMID- 16293845
TI  - What do patients and the public want from primary care?

PMID- 16293846
TI  - Adjuvant trastuzumab for breast cancer: the other side of the coin.

PMID- 16293847
TI  - Adjuvant trastuzumab for breast cancer: an increasingly common ethical and
      economic conundrum.

PMID- 16293848
TI  - Adjuvant trastuzumab for breast cancer: advent of pharmacogenetics raises many
      issues.

PMID- 16293849
TI  - Adjuvant trastuzumab for breast cancer: assessing HER2/neu status incurs more
      costs for treatment.

PMID- 16293850
TI  - Health in Africa: there is more to the crisis.

PMID- 16293851
TI  - Health in Africa: international experience may provoke animosity towards those
      returning home.

PMID- 16293852
TI  - Stockpiling oseltamivir: Roche clarifies data for improved mortality with
      oseltamivir.

PMID- 16293853
TI  - Stockpiling oseltamivir: what is the number needed to treat with oseltamivir to
      prevent one flu death?

PMID- 16293854
TI  - Adjuvant trastuzumab for breast cancer: editorial does not mention health
      economics of drug.

PMID- 16293855
TI  - India plans to audit clinical trials.

PMID- 16293856
TI  - Data are still needed for HPV immunisation programme.

PMID- 16293857
TI  - Postpartum eclampsia of late onset: a complicated case.

PMID- 16293858
TI  - Croatia's brain drain.

PMID- 16293859
TI  - Lady doctors: where are the gentleman doctors?

PMID- 16293860
TI  - Consultants' hours of work: a new perspective.

PMID- 16293861
TI  - CAM before the storm: authors' reply.

PMID- 16293862
TI  - Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil
      versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen
      for high-risk, node-negative breast cancer: treatment results of Intergroup
      Protocol INT-0102.
AB  - PURPOSE: We evaluated the efficacy of cyclophosphamide, methotrexate, and
      fluorouracil (CMF) versus cyclophosphamide, doxorubicin, and fluorouracil (CAF)
      in node-negative breast cancer patients with and without tamoxifen (TAM), overall
      and by hormone receptor (HR) status. PATIENTS AND METHODS: Node-negative patients
      identified by tumor size (> 2 cm), negative HR, or high S-phase fraction (n =
      2,690) were randomly assigned to CMF, CAF, CMF + TAM (CMFT), or CAF + TAM (CAFT).
      Cox regression evaluated overall survival (OS) and disease-free survival (DFS)
      for CAF versus CMF and TAM versus no TAM separately. Two-sided CIs and one-sided
      P values for planned comparisons were calculated. RESULTS: Ten-year estimates
      indicated that CAF was not significantly better than CMF (P = .13) for the
      primary outcome of DFS (77% v 75%; HR = 1.09; 95% CI, 0.94 to 1.27). CAF had
      slightly better OS than CMF (85% v 82%, HR = 1.19 for CMF v CAF; 95% CI, 0.99 to
      1.43); values were statistically significant in the planned one-sided test (P =
      .03). Toxicity was greater with CAF and did not increase with TAM. Overall, TAM
      had no benefit (DFS, P = .16; OS, P = .37), but the TAM effect differed by HR
      groups. For HR-positive patients, TAM was beneficial (DFS, HR = 1.32 for no TAM v
      TAM; 95% CI, 1.09 to 1.61; P = .003; OS, HR = 1.26; 95% CI, 0.99 to 1.61; P =
      .03), but not for HR-negative patients (DFS, HR = 0.81 for no TAM v TAM; 95% CI,
      0.64 to 1.03; OS, HR = 0.79; 95% CI, 0.60 to 1.05). CONCLUSION: CAF did not
      improve DFS compared with CMF; there was a slight effect on OS. Given greater
      toxicity, we cannot conclude CAF to be superior to CMF. TAM is effective in HR
      positive disease, but not in HR-negative disease.

PMID- 16293863
TI  - Phase III trial of epirubicin plus paclitaxel compared with epirubicin plus
      cyclophosphamide as first-line chemotherapy for metastatic breast cancer: United
      Kingdom National Cancer Research Institute trial AB01.
AB  - PURPOSE: To compare the effectiveness and tolerability of epirubicin and
      paclitaxel (EP) with epirubicin and cyclophosphamide (EC) as first-line
      chemotherapy for metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients
      previously untreated with chemotherapy (except for adjuvant therapy) were
      randomly assigned to receive either EP (epirubicin 75 mg/m2 and paclitaxel 200
      mg/m2) or EC (epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2) administered
      intravenously every 3 weeks for a maximum of six cycles. The primary outcome was
      progression-free survival; secondary outcome measures were overall survival,
      response rates, and toxicity. RESULTS: Between 1996 and 1999, 705 patients (353
      EP patients and 352 EC patients) underwent random assignment. Patient
      characteristics were well matched between the two groups, and 71% of patients
      received six cycles of treatment. Objective response rates were 65% for the EP
      group and 55% for the EC group (P = .015). At the time of analysis, 641 patients
      (91%) had died. Median progression-free survival time was 7.0 months for the EP
      group and 7.1 months for the EC group (hazard ratio = 1.07; 95% CI, 0.92 to 1.24;
      P = .41), and median overall survival time was 13 months for the EP group and 14
      months for the EC group (hazard ratio = 1.02; 95% CI, 0.87 to 1.19; P = .8). EP
      patients, compared with EC patients, had more grade 3 and 4 mucositis (6% v 2%,
      respectively; P = .0006) and grade 3 and 4 neurotoxicity (5% v 1%, respectively;
      P < .0001). CONCLUSION: In terms of progression-free survival and overall
      survival, there was no evidence of a difference between EP and EC. The data
      demonstrate no additional advantage to using EP instead of EC as first-line
      chemotherapy for MBC in taxane-naive patients.

PMID- 16293864
TI  - Nomograms to predict pathologic complete response and metastasis-free survival
      after preoperative chemotherapy for breast cancer.
AB  - PURPOSE: To combine clinical variables associated with pathologic complete
      response (pCR) and distant metastasis-free survival (DMFS) after preoperative
      chemotherapy (PC) into a prediction nomogram. PATIENTS AND METHODS: Data from 496
      patients treated with anthracycline PC at the Institut Gustave Roussy were used
      to develop and calibrate a nomogram for pCR based on multivariate logistic
      regression. This nomogram was tested on two independent cohorts of patients
      treated at the M.D. Anderson Cancer Center. The first cohort (n = 337) received
      anthracycline; the second cohort (n = 237) received a combination of paclitaxel
      and anthracycline PC. A separate nomogram to predict DMFS was developed using Cox
      proportional hazards regression model. RESULTS: The pCR nomogram based on
      clinical stage, estrogen receptor status, histologic grade, and number of
      preoperative chemotherapy cycles had good discrimination and calibration in the
      training and the anthracycline-treated validation sets (concordance indices,
      0.77, 0.79). In the paclitaxel plus anthracycline group, when the predicted pCR
      rate was less than 14%, the observed rate was 7.5%; for a predicted rate of > or
      = 38%, the actual rate was 85%. For a predicted rate between 14% to 38%, the
      observed rates were 50% with weekly and 27% with 3-weekly paclitaxel. This
      indicates that patients with intermediate chemotherapy sensitivity benefit the
      most from the optimized schedule of paclitaxel. Patients unlikely to achieve pCR
      to anthracylines remain at low probability for pCR, even after inclusion of
      paclitaxel. The nomogram for DMFS had a concordance index of 0.72 in the
      validation set and outperformed other prediction tools (P = .02). CONCLUSION: Our
      nomograms predict pCR accurately and can serve as a basis to integrate future
      molecular markers into a clinical prediction model.

PMID- 16293865
TI  - Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose
      dense every-2-week adjuvant breast cancer chemotherapy.
AB  - PURPOSE: Dose-dense, every-2-week adjuvant chemotherapy using
      doxorubicin/cyclophosphamide (AC; 60/600 mg/m2 every 2 weeks x four cycles)
      followed by paclitaxel (175 mg/m2 every 2 weeks x four cycles), requiring
      filgrastim on days 3 through 10 of each cycle has been shown to improve survival
      compared with every-3-week treatment schedules but is associated with greater
      risk of RBC transfusion (13%). The role of long-acting hematopoietic growth
      factors in facilitating every-2-week chemotherapy and minimizing hematologic
      toxicity has not been established. PATIENTS AND METHODS: Women with stage I to
      III breast cancer received dose-dense AC --> paclitaxel as neoadjuvant or
      adjuvant chemotherapy. Patients received pegfilgrastim 6 mg subcutaneous (SQ) on
      day 2 of each cycle. Darbepoetin alfa was initiated at 200 microg SQ every 2
      weeks for hemoglobin < or = 12 g/dL, and administered thereafter, according to a
      preplanned algorithm. The primary end points were to evaluate the percentage of
      patients with febrile neutropenia and the percentage of patients requiring RBC
      transfusion. RESULTS: Among 135 women treated on this single arm study, there
      were two cases of febrile neutropenia (incidence 1.5%). No patients received RBC
      transfusion. Darbepoetin alfa therapy was initiated in 92% of patients. The
      modest leukocytosis seen during paclitaxel cycles was attributable, in part, to
      corticosteroid premedication. Other toxicity and dose-delivery were similar to
      dose-dense AC --> paclitaxel in Cancer and Leukemia Group B 9741. CONCLUSION:
      Pegfilgrastim and darbepoetin alfa are effective and safe in facilitating every-2
      week AC --> paclitaxel, minimizing rates of febrile neutropenia and RBC
      transfusion.

PMID- 16293866
TI  - Prognostic relevance of response evaluation using [18F]-2-fluoro-2-deoxy-D
      glucose positron emission tomography in patients with locally advanced non-small
      cell lung cancer.
AB  - PURPOSE: The objective of this study was to determine the accuracy of (early)
      response measurements using [18F]-2-fluoro-2-deoxy-D-glucose positron emission
      tomography (18FDG PET) with respect to survival of patients with stage IIIA-N2
      non-small-cell lung cancer (NSCLC) undergoing induction chemotherapy (IC), with a
      comparative analysis of PET methods. PATIENTS AND METHODS: In a prospective
      multicenter study, PET was performed in patients before IC and after one and
      three cycles. Computed tomography (CT) was performed before and after IC. Glucose
      consumption (metabolic rate of glucose [MRglu]) was measured using Patlak
      graphical analysis and correlated with simplified methods. Mediastinal lymph node
      (MLN) status was assessed visually. Cox proportional hazards analysis was used to
      determine the prognostic relevance of CT and PET measures of response with
      respect to survival. RESULTS: Complete PET data sets were available in 47
      patients. Median survival was 21 months. MLN status after IC by PET predicted
      survival (hazard ratio [HR], 2.33; 95% CI, 1.04 to 5.22; P = .04) in contrast
      with CT (HR, 1.87; 95% CI, 0.81 to 4.30; P = .14). Residual MRglu after IC proved
      to be the best prognostic factor (HR, 1.95; 95% CI, 1.28 to 2.97; P = .002).
      Multivariate stepwise analysis showed that PET identified prognostically
      different strata in patients considered responsive according to CT. Residual
      MRglu after one cycle selected patients with different outcomes (HR, 2.04; 95%
      CI, 1.18 to 3.52; P = .01). Simplified quantitative 18FDG PET methods were
      correlated with Patlak graphical analysis during and after therapy (r > or =
      0.90). CONCLUSION: 18FDG PET has additional value over CT in monitoring response
      to IC in patients with stage IIIA-N2 NSCLC, and it seems feasible to predict
      survival early during IC. Simple semiquantitative and complex PET methods perform
      equally well.

PMID- 16293867
TI  - Ifosfamide, carboplatin, and etoposide with midcycle vincristine versus standard
      chemotherapy in patients with small-cell lung cancer and good performance status:
      clinical and quality-of-life results of the British Medical Research Council
      multicenter randomized LU21 trial.
AB  - PURPOSE: Ifosfamide, carboplatin, etoposide, and vincristine, alone and in
      combination, are highly active against small-cell lung cancer (SCLC). This trial
      was designed to investigate whether survival could be improved by a regimen of
      all four drugs (ICE-V) compared with standard chemotherapy in patients with SCLC
      and good performance status, and to assess the patients' quality of life (QL).
      PATIENTS AND METHODS: Patients were randomly assigned to receive six cycles of
      either ICE-V at 4-week intervals without dose reduction or standard chemotherapy
      administered according to local practice. The recommended standard control
      regimens were cyclophosphamide, doxorubicin, and etoposide; and cisplatin and
      etoposide. RESULTS: A total of 402 patients were randomly assigned, and 350 (87%)
      patients have died. Overall survival was longer in the ICE-V group (hazard ratio,
      0.74; 95% CI, 0.60 to 0.91; P = .0049), median survival was 15.6 months in the
      ICE-V group and 11.6 months in the control group, and 2-year survival rates were
      20% and 11%, respectively. There was no evidence that the relative survival
      benefit for ICE-V was less in extensive-stage than in limited-stage patients. An
      increased rate of septicemia was reported in the ICE-V group (15% v 7% in the
      control group), but this did not result in an increase in reported treatment
      related deaths (four patients [2%] in both groups). The findings on QL were
      broadly similar in both groups, with some benefit in favor of ICE-V. CONCLUSION:
      Compared with standard chemotherapy, the ICE-V regimen improves overall survival
      without QL penalties, despite an increased but manageable level of toxicity.

PMID- 16293868
TI  - Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine
      in the treatment of locally advanced or metastatic non-small-cell lung cancer:
      the Swedish Lung Cancer Study Group.
AB  - PURPOSE: This phase III study compared overall survival in patients with locally
      advanced or metastatic non-small-cell lung cancer (NSCLC) when treated with
      single-agent gemcitabine versus gemcitabine/carboplatin. Secondary objectives
      were to compare response, time to progression, toxicity, and quality of life.
      PATIENTS AND METHODS: Chemotherapy-naive patients received either gemcitabine
      alone (1,250 mg/m2 on days 1 and 8; gemcitabine arm) or with carboplatin (area
      under the curve 5 on day 1; GC arm) every 21 days. RESULTS: Demographics and
      disease characteristics of 334 randomly assigned patients were comparable on both
      arms. An intent-to-treat analysis showed significantly better overall survival
      (log-rank P = .0205) and 2-year survival (15% v 5%; P = .009) favoring the GC
      arm. Per Cox multivariate analysis, only two covariates, treatment arm (GC v G)
      and baseline performance status (0 or 1 v 2), independently influenced survival.
      Per-protocol analyses showed significantly longer median time to progression (5.7
      v 3.9 months; P = .0001) and significantly higher objective response rate (29.6 v
      11.3%; P < .0001) in the GC arm. Grade 3 to 4 leucopenia and thrombocytopenia
      were significantly more pronounced in the GC arm (P for both variables < .001)
      but importantly without associated increases in fever, infection, bleeding, or
      hospitalizations. There was no discernible difference in global quality-of-life
      patterns between treatment arms. CONCLUSION: In advanced NSCLC,
      gemcitabine/carboplatin therapy resulted in significant survival benefit compared
      with single-agent gemcitabine without undue increase in toxicity.

PMID- 16293870
TI  - Epidemiology of bronchioloalveolar carcinoma: improvement in survival after
      release of the 1999 WHO classification of lung tumors.
AB  - PURPOSE: Classification changes for bronchioloalveolar carcinoma (BAC) by the WHO
      in May 1999 narrowed its definition. This study was undertaken in an attempt to
      characterize the impact of these changes on the epidemiology of BAC. PATIENTS AND
      METHODS: This retrospective study involves data analysis from the population
      based Cancer Surveillance Programs of three Southern California counties from
      1995 to 2003. BAC cases diagnosed after May 1999 are compared with BAC cases
      before that time by clinicopathologic variables including survival. RESULTS:
      Incident cases (11,969) of non-small-cell lung cancer (NSCLC) were analyzed,
      including 626 cases of BAC (5.2%). Median overall survival (OS) for BAC patients
      diagnosed after May 1999 (> 53 months) was significantly improved over median OS
      for BAC patients before May 1999 (32 months; P = .012). This survival benefit
      remained after adjustment for sex, smoking status, and stage at presentation
      (hazard ratio for time of diagnosis before May 1999 compared with a diagnosis
      after May 1999 = 1.43; P = .015). Median OS for non-BAC NSCLC patients diagnosed
      before May 1999 (9 months) did not differ from the median OS of such patients
      afterwards (10 months; P = .09). CONCLUSION: This epidemiologic study is the
      first to demonstrate a survival advantage for BAC patients diagnosed after May
      1999 compared with BAC patients diagnosed before this time-a finding that
      persists after adjustment for sex, smoking status, and stage at presentation. We
      believe that this observed survival benefit likely reflects changes in the
      revised 1999 WHO classification.

PMID- 16293869
TI  - Phase III study of second-line chemotherapy for advanced non-small-cell lung
      cancer with weekly compared with 3-weekly docetaxel.
AB  - PURPOSE: A phase III study to determine whether a weekly docetaxel schedule
      improves the therapeutic index compared with the classic 3-weekly schedule.
      PATIENTS AND METHODS: Patients with stage IIIB-IV non-small-cell lung cancer
      (NSCLC) were randomly assigned to docetaxel 75 mg/m2 on day 1 every 3 weeks (3
      weekly) and 35 mg/m2 on days 1, 8, and 15 (weekly) for < or = eight cycles. End
      points included survival (primary), toxicity, and response. RESULTS: Of 215
      patients enrolled, 208 (103 in the 3-weekly arm and 105 in the weekly arm) were
      assessable for response. At baseline, 24.5% of patients (51 out of 208) had
      received prior paclitaxel therapy and 43.3% of patients (90 out of 208) had been
      progression-free for more than 3 months after first-line therapy. After 12
      months' follow-up, median survival was 6.3 months (95% CI, 4.68 to 7.84 months)
      with 3-weekly docetaxel and 9.2 months (95% CI, 5.83 to 12.59 months) with weekly
      docetaxel (P = .07) after a median of four (range, one to eight) and two (range,
      one to eight) treatment cycles, respectively. Overall, response rates were 12.6%
      v 10.5% with 3-weekly versus weekly docetaxel. Significantly fewer patients
      reported grade 3 to 4 toxicities with weekly docetaxel versus 3-weekly docetaxel
      (P < or = .05). There were significantly lower rates of grade 3 to 4 anemia (P <
      or = .05), leucopenia (P < .0001), and neutropenia (P < or = .001) with weekly
      versus 3-weekly treatment. No grade 3 to 4 thrombocytopenia or mucositis was
      reported. CONCLUSION: Weekly docetaxel 35 mg/m2 demonstrated similar efficacy and
      better tolerability than standard 3-weekly docetaxel 75 mg/m2 and can be
      recommended as a feasible alternative second-line treatment option for patients
      with advanced NSCLC.

PMID- 16293871
TI  - Patterns of treatment failure in pediatric and young adult patients with
      Hodgkin's disease: local disease control with combined-modality therapy.
AB  - PURPOSE: Refinement in managing pediatric Hodgkin's disease (HD) requires
      understanding of factors associated with local treatment failure. This study
      defines the cumulative incidence (CI) of local failure (LF) and prognostic
      factors for pediatric patients treated for HD with combined-modality therapy
      (CMT). PATIENTS AND METHODS: We enrolled 195 patients onto two prospective
      studies at St Jude Children's Research Hospital between 1990 and 2000. Patients
      received CMT with chemotherapy (vinblastine, doxorubicin, methotrexate, and
      prednisone [VAMP]; vinblastine, etoposide, prednisone, and doxorubicin; or
      VAMP/cyclophosphamide, vincristine, and procarbazine) and involved-field
      radiation therapy delivered to initial site(s) of disease on the basis of early
      response. Sites of disease involvement, treatment, and sites of failure were
      confirmed from the patients' medical record, imaging, and radiotherapy treatment
      records. We estimated the overall survival, event-free survival, and CI of LF.
      RESULTS: With a median follow-up of 7.6 years, the CI of LF was 10.9% and 11.6%
      at 5 and 10 years, respectively. Twenty-seven (14%) of 195 patients experienced
      recurrence of HD, and 22 (81%) of those experienced LF. Bulky mediastinal disease
      greater than one third transthoracic diameter predicted a higher incidence of LF,
      but did not predict failure in the mediastinum. Male sex, low initial hemoglobin,
      and bulky mediastinal disease were prognostic indicators of LF. Attenuation of
      radiation dose to 15 Gy based on response provides excellent infield control.
      CONCLUSION: CMT provides excellent local disease control in children and young
      adults with HD. LF remains a primary site of disease recurrence, with male sex,
      low initial hemoglobin, and bulky mediastinal disease predicting for LF.

PMID- 16293872
TI  - Tumor necrosis factor and lymphotoxin alfa genetic polymorphisms and outcome in
      pediatric patients with non-Hodgkin's lymphoma: results from Berlin-Frankfurt
      Munster Trial NHL-BFM 95.
AB  - PURPOSE: To analyze the association of genetic variation within the tumor
      necrosis factor (TNF -308 [G-->A]) and lymphotoxin alfa (LT-a +252 [A-->G]) genes
      with outcome in non-Hodgkin's lymphoma of childhood and adolescence. PATIENTS AND
      METHODS: Genotyping of the TNF -308 (G-->A) and LT-a +252 (A-->G) polymorphisms
      in patients (n = 488) enrolled onto the German-Austrian-Swiss multicenter trial
      NHL-BFM 95 from April 1996 to January 2000 was performed by polymerase chain
      reaction with subsequent restriction fragment length polymorphism analysis on DNA
      from tumor-free specimen. RESULTS: In patients with Burkitt's lymphoma (BL) and B
      cell acute lymphoblastic leukemia (B-ALL; n = 219, 211 eligible patients),
      patients carrying at least two variant alleles (high-producer haplotypes) had an
      increased risk of events: probability of event-free survival (pEFS) at 3 years
      was 81% (SE = 5%), compared with 91% (SE = 2%) in low-producer haplotypes (P =
      .018). In BL/B-ALL with high tumor load (lactate dehydrogenase [LDH] > or = 500
      U/L; n = 104), pEFS was 69% (SE = 8%) in high-producer versus 85% (SE = 4%) in
      low-producer haplotypes (P = .05). In multivariate analysis including risk
      factors for events (LDH > or = 500 U/L, CNS involvement, methotrexate infusion
      regimen), TNF -308/LT-alpha +252 haplotype kept prognostic relevance: patients
      with high-producer haplotypes had a 2.34-fold increase in risk of events (P =
      .048). The TNF -308 (G-->A) and LT-alpha +252 (A-->G) polymorphisms were not
      associated with pEFS in lymphoblastic lymphoma (n = 101), anaplastic large-cell
      lymphoma (n = 67), or diffuse large B-cell lymphoma (n = 65), nor with therapy
      related toxicity. CONCLUSION: The TNF -308 (G-->A) and LT-a +252 (A-->G)
      polymorphisms were negative prognostic factors in pediatric BL/B-ALL. Among
      patients with serum LDH > or = 500 U/L, haplotype analysis further determined
      patients at risk for events.

PMID- 16293874
TI  - Pediatric phase I trials in oncology: an analysis of study conduct efficiency.
AB  - PURPOSE: To determine the efficacy and safety of pediatric phase I oncology
      trials in the era of dose-intensive chemotherapy and to analyze how efficiently
      these trials are conducted. METHODS: Phase I pediatric oncology trials published
      from 1990 to 2004 and their corresponding adult phase I trials were reviewed.
      Dose escalation schemes using fixed 30% dose increments were studied to
      theoretically determine whether trials could be completed utilizing fewer
      patients and dose levels. RESULTS: Sixty-nine pediatric phase I oncology trials
      enrolling 1,973 patients were identified. The pediatric maximum-tolerated dose
      (MTD) was strongly correlated with the adult MTD (r = 0.97). For three-fourths of
      the trials, the pediatric and adult MTD differed by no more than 30%, and for
      more than 85% of the trials, the pediatric MTD was less than or equal to 1.6
      times the adult MTD. The median number of dose levels studied was four (range,
      two to 13). The overall objective response rate was 9.6%, the likelihood of
      experiencing a dose-limiting toxicity was 24%, and toxic death rate was 0.5%.
      CONCLUSION: Despite the strong correlation between the adult and pediatric MTDs,
      more than four dose levels were studied in 40% of trials. There appeared to be
      little value in exploring dose levels greater than 1.6 times the adult MTD.
      Limiting pediatric phase I trials to a maximum of four doses levels would
      significantly shorten the timeline for study conduct without compromising safety.

PMID- 16293873
TI  - Pediatric malignant peripheral nerve sheath tumor: the Italian and German soft
      tissue sarcoma cooperative group.
AB  - PURPOSE: To assess the value of chemotherapy and radiotherapy in children with
      malignant peripheral nerve sheath tumors (MPNSTs) and to identify risk factors
      associated with outcome. PATIENTS AND METHODS: A total of 167 untreated eligible
      patients enrolled onto the Italian and German studies between 1975 and 1998
      entered this analysis. Seventeen percent of patients had neurofibromatosis type 1
      (NF1). Chemotherapy was administered to 74% of patients; radiotherapy was
      administered to 38% of patients. RESULTS: With a median follow-up of 7 years, 5
      year overall survival (OS) and progression-free survival (PFS) were 51% and 37%,
      respectively. The 5-year OS and PFS by Intergroup Rhabdomyosarcoma Study (IRS)
      groupings were as follows: group I, 82% and 61%; group II, 62% and 37%; group
      III, 32% and 27%; group IV, 26% and 21%, respectively. Univariate analysis
      identified IRS groups, size, invasiveness, primary site, age, and presence of NF1
      as prognostic factors; multivariate analysis identified absence of NF1, tumor
      invasiveness T1, IRS groups I to II and extremity of primary site as independent
      favorable factors for OS. A trend was observed toward a benefit from radiotherapy
      after initial gross resection. The overall response rate to primary chemotherapy,
      including minor responses, in group III patients was 45%. CONCLUSION: MPNST is an
      aggressive tumor for which complete surgical resection is the mainstay of
      successful treatment. Postoperative radiotherapy may have a role in improving
      local control in patients with minimal residual tumor. The reported responses to
      primary chemotherapy suggest that it may be effective in patients with tumor
      considered unresectable at diagnosis.

PMID- 16293875
TI  - Phase II study of oxaliplatin for treatment of patients with mucosa-associated
      lymphoid tissue lymphoma.
AB  - PURPOSE: Various chemotherapeutic regimens have been applied for treatment of
      mucosa-associated lymphoid tissue (MALT) lymphoma, but no standard regimen has
      been identified to date. In view of the activity of oxaliplatin (L-OHP) in
      various types of lymphoma, we performed a phase II study to evaluate the activity
      of L-OHP for treatment of MALT lymphoma. The primary objective of this study was
      to determine the objective response rate according to WHO standard criteria.
      PATIENTS AND METHODS: A total of 16 patients with MALT lymphoma of various sites
      of origin (four of the ocular adnexa, five of the salivary glands, three of the
      stomach, two of the lung, and one of the colon and the breast) were administered
      L-OHP at a dose of 130 mg/m2 infused during 2 hours every 3 weeks. Restaging was
      performed every two cycles; treatment was continued until complete remission (CR)
      or for a maximum of six cycles in responders. RESULTS: Sixty-five cycles were
      administered (median, four; range, two to six); toxicity consisted of transient
      sensory neuropathy in eight patients and nausea/emesis WHO grade 2 in two
      patients, whereas hematologic adverse effects (thrombocytopenia and
      leukocytopenia grade 2) occurred in only one patient each. Fifteen patients
      responded to chemotherapy, with nine achieving CR (56%), six (37.5%) achieving
      partial response, and one achieving stable disease; the median time to response
      was 4 months (range; 2 to 4 months). CONCLUSION: These data suggest L-OHP is a
      highly active agent for treatment of MALT lymphoma. However, a longer follow-up
      is needed to judge whether these remissions are durable.

PMID- 16293877
TI  - Mammography, breast ultrasound, and magnetic resonance imaging for surveillance
      of women at high familial risk for breast cancer.
AB  - PURPOSE: To compare the effectiveness of mammography, breast ultrasound, and
      magnetic resonance imaging (MRI) for surveillance of women at increased familial
      risk for breast cancer (lifetime risk of 20% or more). PATIENTS AND METHODS: We
      conducted a surveillance cohort study of 529 asymptomatic women who, based on
      their family history and/or mutational analysis, were suspected or proven to
      carry a breast cancer susceptibility gene (BRCA). A total of 1,542 annual
      surveillance rounds were completed with a mean follow-up of 5.3 years. Diagnostic
      accuracies of the three imaging modalities used alone or in different
      combinations were compared. RESULTS: Forty-three breast cancers were identified
      in the total cohort (34 invasive, nine ductal carcinoma-in-situ). Overall
      sensitivity of diagnostic imaging was 93% (40 of 43 breast cancers); overall node
      positive rate was 16%, and one interval cancer occurred (one of 43 cancers, or
      2%). In the analysis by modality, sensitivity was low for mammography (33%) and
      ultrasound (40%) or the combination of both (49%). MRI offered a significantly
      higher sensitivity (91%). The sensitivity of mammography in the higher risk
      groups was 25%, compared with 100% for MRI. Specificity of MRI (97.2%) was
      equivalent to that of mammography (96.8%). CONCLUSION: Mammography alone, and
      also mammography combined with breast ultrasound, seems insufficient for early
      diagnosis of breast cancer in women who are at increased familial risk with or
      without documented BRCA mutation. If MRI is used for surveillance, diagnosis of
      intraductal and invasive familial or hereditary cancer is achieved with a
      significantly higher sensitivity and at a more favorable stage.

PMID- 16293876
TI  - Assessment of a dietary questionnaire in cancer patients receiving cytotoxic
      chemotherapy.
AB  - PURPOSE: Few studies have examined the influence of diet on survival and
      chemotherapy-associated toxicities in patients with cancer. Although several
      comprehensive dietary questionnaires have been validated and calibrated in
      healthy populations, similar studies have not been performed among cancer
      patients. METHODS: Two hundred patients with colorectal, breast, or
      neuroendocrine cancer undergoing treatment with cytotoxic chemotherapy completed
      a self-administered, 131-item, semiquantitative food frequency questionnaire.
      Using the questionnaire, we calculated dietary intakes of carotenoids,
      tocopherols, and fatty acids, and correlated these values with relevant
      biomarkers measured in simultaneously collected plasma specimens. RESULTS: The
      Pearson correlation coefficients for various carotenoids as measured by the
      questionnaire, with the corresponding measurements in plasma specimens, ranged
      from 0.33 to 0.44 (all P < .001), adjusted for total energy intake, body mass
      index, age, sex, smoking status, and total plasma cholesterol. Similarly, the
      adjusted correlation between self-reported total vitamin E intake and plasma
      alpha-tocopherol was 0.34 (P < .001). Correlations between questionnaire and
      plasma measurements of trans-fat, eicosapentaenoic acid, and docosahexaenoic acid
      were 0.55, 0.29, and 0.42 (all P < .001), respectively. These levels of
      correlation are consistent with those reported in similar studies of self
      reported diet in otherwise healthy populations. CONCLUSION: Among patients with
      cancer receiving cytotoxic chemotherapy, questionnaire-based measurements of
      various micronutrients and dietary factors appeared to predict meaningful
      differences in the corresponding measurements in plasma specimens. This dietary
      questionnaire could offer an informative and practical means for assessing the
      influence of diet in cancer patients receiving chemotherapy.

PMID- 16293878
TI  - Surgical risk factors in primary surgery for localized neuroblastoma: the LNESG1
      study of the European International Society of Pediatric Oncology Neuroblastoma
      Group.
AB  - PURPOSE: Although tumor resection is the mainstay of treatment for localized
      neuroblastoma, there are no established guidelines indicating which patients
      should be operated on immediately and which should undergo surgery after tumor
      reduction with chemotherapy. In an effort to develop such guidelines, the LNESG1
      study defined surgical risk factors (SRFs) based on the imaging characteristics.
      PATIENTS AND METHODS: A total of 905 patients with suspected localized
      neuroblastoma were registered by 10 European countries between January 1995 and
      October 1999; 811 of 905 patients were eligible for this analysis. RESULTS:
      Information on SRFs was obtained for 719 of 811 patients; 367 without and 352
      with SRFs. Of these 719 patients, 201 patients (four without and 197 with SRFs)
      underwent biopsy only. An attempt at tumor excision was made in 518 patients: 363
      of 367 patients without and 155 of 352 patients with SRFs (98.9% v 44.0%).
      Complete excision was achieved in 271 of 363 patients without and in 72 of 155
      patients with SRF (74.6% v 46.4%), near-complete excision was achieved in 81 and
      61 patients (22.3% v 39.3%), and incomplete excision was achieved in 11 and 22
      patients (3.0% v 14.2%), respectively. There were two surgery-related deaths.
      Nonfatal surgery-related complications occurred in 45 of 518 patients (8.7%) and
      were less frequent in patients without SRFs (5.0% v 17.4%). Associated surgical
      procedures were also less frequent in patients without SRFs (1.6% v 9.7%).
      CONCLUSION: The adoption of SRFs as predictors of adverse surgical outcome was
      validated because their presence was associated with lower complete resection
      rate and greater risk of surgery-related complications. Additional studies aiming
      to better define the surgical approach to localized neuroblastoma are warranted.

PMID- 16293879
TI  - Systematic review of the treatment of cancer-associated anorexia and weight loss.
AB  - PURPOSE: We systematically assessed the efficacy and safety of appetite
      stimulants in the management of cancer-related anorexia. Literature databases
      were searched for randomized controlled trials of appetite stimulants in the
      treatment of cancer anorexia. MATERIALS AND METHODS: Studies were graded
      according to quality. Fifty-five studies met inclusion criteria. RESULTS: Only
      two drugs have evidence to support their use for anorexia (progestins and
      corticosteroids). There is strong evidence against the use of hydrazine sulfate.
      The outcomes of these trials have been mixed and patient population
      heterogeneous. CONCLUSION: The optimal dose, time to start, and duration of
      treatment for many appetite stimulants for cancer anorexia is still unknown. A
      more systematic approach to research methodology with universal outcome measure
      and prospective randomized studies are need. Combination regimens are needed but
      this cannot at the present time be supported by the data presented.

PMID- 16293880
TI  - Pathogenesis of myelofibrosis with myeloid metaplasia.
AB  - The primary disease process in myelofibrosis with myeloid metaplasia (MMM) is
      clonal myeloproliferation with varying degrees of phenotypic differentiation.
      This is characteristically accompanied by secondary intramedullary collagen
      fibrosis, osteosclerosis, angiogenesis, and extramedullary hematopoiesis. Modern
      clonality studies have confirmed the multipotent stem-cell origin of the
      neoplastic process in MMM. The nature of the specific oncogenic mutation(s) is
      currently being unraveled with the recent discovery of an association between a
      somatic point mutation of JAK2 tyrosine kinase (V617F) and bcr/abl-negative
      myeloproliferative disorders, including MMM. The pathogenetic mechanisms that
      underlie the secondary bone marrow stromal changes in MMM are also incompletely
      understood. Mouse models of this latter disease aspect have been constructed by
      either in vivo overexpression of thrombopoietin (TPOhigh mice) or megakaryocyte
      lineage restricted underexpression of the transcription factor GATA-1 (GATA-1low
      mice). Gene knockout experiments using such animal models have suggested the
      essential role of hematopoietic cell-derived transforming growth factor beta1 in
      inducing bone marrow fibrosis and stromal cell-derived osteoprotegerin in
      promoting osteosclerosis. However, experimental myelofibrosis in mice does not
      recapitulate clonal myeloproliferation that is fundamental to human MMM. Other
      cytokines that are implicated in mediating myelofibrosis and angiogenesis in MMM
      include basic fibroblast, platelet-derived, and vascular endothelial growth
      factors. It is currently assumed that such cytokines are abnormally released from
      clonal megakaryocytes as a result of a pathologic interaction with neutrophils
      (eg, emperipolesis). This latter phenomenon, through neutrophil-derived elastase,
      could also underlie the abnormal peripheral-blood egress of myeloid progenitors
      in MMM.

PMID- 16293881
TI  - Side effects related to cancer treatment: CASE 1. Hepatitis following treatment
      with gefitinib.

PMID- 16293882
TI  - Side effects related to cancer treatment: CASE 2. Splenic rupture following
      pegfilgrastim.

PMID- 16293883
TI  - Side effects related to cancer treatment: CASE 3. Primary cerebral lymphoma after
      radiotherapy for recurrent meningioma.

PMID- 16293884
TI  - Is the statistical difference clinically relevant?

PMID- 16293885
TI  - Burkitt's lymphoma and previous AIDS-defining illnesses are not prognostic
      factors in AIDS-related non-Hodgkin's lymphoma.

PMID- 16293886
TI  - Variability and sample size requirements for health-related quality-of-life
      measures: understanding the challenges facing investigators.

PMID- 16293887
TI  - Computer modeling is no substitute for randomized clinical trials for decision
      making in early breast cancer hormonal therapy.

PMID- 16293888
TI  - Optimum use of aromatase inhibitors in the adjuvant treatment of early breast
      cancer.

PMID- 16293889
TI  - Is there really enough evidence to abandon surgery after radiation chemotherapy
      in esophageal cancer?

PMID- 16293891
TI  - Frequency and prediction of abnormal findings on neuroimaging of infants with
      bulging anterior fontanelles.
AB  - OBJECTIVES: This study sought to determine the frequency of clinically
      significant abnormal findings on neuroimaging using neurosonography (NS) in
      infants with bulging anterior fontanelles (BAFs) and to identify infants at high
      or low risk for clinically significant abnormal findings on neuroimaging.
      METHODS: NS was performed in 45 consecutive infants with BAFs brought to the
      emergency department of a tertiary care hospital. NS reports were categorized as
      normal, clinically insignificant abnormal, or clinically significant abnormal.
      For each patient, demographic data, laboratory test results, and clinical
      diagnosis and outcome were obtained for analysis. RESULTS: Eighteen febrile and
      27 nonfebrile infants with BAFs were evaluated. Clinically significant abnormal
      findings on NS were noted in 16 of 45 patients (36%), five of whom were febrile
      and 11 of whom were nonfebrile. Brain edema resulting from infection was the most
      common finding on NS. Univariate analysis indicated that age younger than two
      months in febrile patients and abnormal findings on neurologic examination in
      nonfebrile patients were significant clinical predictors for clinically
      significant abnormal findings on NS in infants with BAFs. Patients presenting
      with either of these clinical predictors were identified as high risk for
      abnormal findings on NS. Of the high-risk patients, 15 of 17 patients (88%) had
      clinically significant abnormal findings on NS, compared with one of 28 patients
      (4%) in the low-risk group. CONCLUSIONS: This study shows a 36% prevalence of
      clinically significant abnormal findings on NS in infants with BAFs. Emergent
      neuroimaging should be considered for infants who meet high-risk criteria: 1)
      febrile children younger than two months or 2) nonfebrile children with abnormal
      findings on neurologic examination.

PMID- 16293890
TI  - Transfer of very low density lipoprotein-associated phospholipids to activated
      human platelets.
AB  - LDL-associated phospholipids (PLs) may be transferred into platelets. In this
      work, we characterized the role of VLDLs as PL donors. VLDL transferred
      radiolabeled PLs to platelets in a temperature- and concentration-dependent
      manner. LPL stimulated this process through its action on VLDL lipolysis, because
      it was abolished by tetrahydrolipstatin. LPL also stimulated the platelet
      production of thromboxane B2 (TXB2). Both LPL actions were inhibited in the
      presence of fatty acid-free albumin, suggesting that they were attributable to
      fatty acids generated during VLDL lipolysis. To study the relationship between PL
      transfers and platelet activation, we performed incubations in the presence of
      HDL, a physiological acceptor of PL released from VLDL. HDL antagonized the
      transfer of PL from VLDL to platelets but had no effect on the production of
      TXB2, suggesting that PL transfers were driven by platelet activation. Confirming
      this idea, thrombin stimulated both the production of TXB2 and the transfers of
      PL. In conclusion, VLDL can transfer PL to platelets. These transfers are
      stimulated by LPL and thrombin through their action on platelet activation. They
      might be enhanced in pathologies characterized by increased VLDL concentrations.

PMID- 16293892
TI  - Regional impact of Hurricane Isabel on emergency departments in coastal
      southeastern Virginia.
AB  - OBJECTIVES: On September 18, 2003, Hurricane Isabel made landfall as a category 2
      hurricane over the mid-Atlantic region, generating record conditions for the
      region's 27 years of monitoring. The purpose of this study was to investigate the
      impact of the hurricane on the number and type of emergency department (ED)
      patient visits and its impact on hospital admission rate from the day of landfall
      to day 5 postlandfall. Comparisons were made with a control group, which
      comprised average daily ED census during the six-month period preceding landfall
      and the average daily admission rates for the preceding six months. METHODS:
      Designed as an observational cohort study, daily ED patient visits and admissions
      through the ED were tracked from the day of landfall to day 5 postlandfall. The
      study population included all ED patient visits at a six-hospital urban health
      care system, including a Level 1 trauma center in the coastal southeastern region
      of Virginia, with an aggregate annual ED volume of 261,000. Daily patient
      volumes, complaint categories, and admission rates were measured during the study
      period and compared with a control population that included average daily patient
      volumes, complaint categories, and admission rates at the same facilities for six
      months before landfall. During a 30-day postlandfall period, 63 emergency
      physicians on staff at the study hospitals were sent an ad hoc survey and asked
      to report their experiences if they worked during the study period. The survey
      included requests for future preparedness recommendations based on their
      experiences and are reported. RESULTS: During the six-month period preceding
      Hurricane Isabel, the average number of aggregate ED visits per day was 670. The
      average daily number of patient visits by complaint category included six major
      traumas, 483 medical complaints, 169 minor traumas, and 13 psychiatric
      complaints. On the day of landfall, the total aggregate ED volume was 359 (-46%),
      which included two (-66%) major traumas, 263 (-46%) medical complaints, 88 (-48%)
      minor traumas, and six (-54%) psychiatric complaints. During the subsequent four
      days postlandfall, there was a significant increase in average daily aggregate ED
      census of 840 (+25%) patient visits, which included three (-50%) major traumas,
      564 (+17%) medical complaints, 263 (+57%) minor traumas, and ten (-23%)
      psychiatric complaints. The largest single-day increase in ED visits was day 1
      postlandfall, with a 35% increase in daily volume (905 patient visits). The
      percentage of admissions from the ED to an inpatient unit on the day of landfall
      also demonstrated a significant increase (19%) compared with the control group
      (13%). Admission rates through the ED had appeared to normalize on day 1
      postlandfall (12%). Response rate to the ad hoc physician survey by those who
      worked during the study period was 31.2% (10 of 32). The most common problem
      areas reported included communication failures, access to on-call personnel, and
      provider and nursing understaffing during the immediate postlandfall period.
      CONCLUSIONS: A significant overall reduction in ED visits by almost half the
      typical average volume was noted on the day of landfall (-46%). During the four
      days immediately following landfall, however, there was a marked increase in the
      overall ED census, with a particularly high increase on day 1 postlandfall. The
      largest complaint category increase was minor trauma (+57%). Hospital admission
      rates were highest on the day of landfall and seemed to return to baseline on day
      1 postlandfall. These data may be useful for structuring ED personnel and
      hospital resource allocation to better serve its community during hurricane
      preparedness planning.

PMID- 16293893
TI  - The paradox of the nested pediatric emergency department.
AB  - OBJECTIVES: Nested pediatric emergency departments (nPEDs) are defined as
      dedicated treatment areas operating during peak pediatric hours within general
      emergency departments (EDs). This study examined three staffing models for nPEDs
      and their impact on pediatric encounters. METHODS: Three models were applied to
      children younger than 37 months presenting to the ED of an urban community
      hospital over one year. In the nPED, physicians cared only for nPED patients. In
      the restricted (rPED) model, physicians cared only for pediatric patients
      presenting outside nPED hours. In the total ED (tED) model, physicians treated
      all pediatric patients regardless of time. Full-time equivalent pediatric
      encounters, potential neonatal lumbar punctures, and illness severity were
      determined for all models. Statistical analysis was performed by analysis of
      variance and chi-square test. RESULTS: For the 3,389 eligible ED visits, the
      number of annual patient encounters per full-time equivalent was 1,236 for the
      nPED, 805 for the tED, and 336 for the rPED (p < 0.001). Physicians practicing
      only in the nPED treated 3.7 times the number of children younger than 37 months
      than did physicians in the rPED model and 1.5 times the number than did
      physicians in the tED model. Spending 10% of total practice hours in the nPED
      would increase pediatric encounters 26% for rPED physicians, while practicing 25%
      of time in the nPED would increase pediatric encounters 67% and equate to 45% of
      nPED encounters. An nPED physician could expect to perform 17 neonatal lumbar
      punctures, compared with ten for a tED physician and four for an rPED physician
      (p < 0.001). There was no significant difference in severity of illness for the
      three models. CONCLUSIONS: Physicians practicing in facilities that include an
      nPED must dedicate some portion of their practice to the nPED to maintain
      equivalent pediatric encounters.

PMID- 16293894
TI  - Histologic effects of laser-assisted topical anesthesia in a porcine model.
AB  - OBJECTIVES: A handheld laser device that removes the stratum corneum, the major
      barrier to transdermal absorption, has recently been approved to assist with
      topical anesthesia before painful procedures such as intravenous cannulation. The
      authors assessed the cutaneous histomorphologic effects of the laser device and
      the ability of the laser-treated skin to resist infection in a porcine model.
      METHODS: This was a blinded, randomized animal experiment using isoflurane
      anesthetized young domestic pigs. The ventral surface of the animals was
      irradiated multiple times with a lightweight, portable erbium yttrium-aluminum
      garnet unit or a sham laser. One third of the wounds were inoculated with a
      Staphylococcus aureus suspension. The treated areas were then covered with a dry
      dressing, and full-thickness biopsy specimens of the treated areas were obtained
      immediately after treatment and at three, seven, ten, and 14 days for blinded
      histopathologic evaluation using hematoxylin and eosin staining and electron
      microscopy. Quantitative bacterial counts were obtained at three days in wounds
      exposed to bacteria. Main outcomes were quantitative bacterial counts, presence
      of cellular necrosis, epidermal integrity, and dermal scarring. Data analysis was
      conducted with descriptive statistics. RESULTS: Laser irradiation resulted in
      immediate disruption of the cornified layer of the skin and necrosis of the
      stratum spinosum in all treated areas. There were also focal areas of vacuolar
      alteration of the basal one third of the epidermis. There was no evidence of any
      damage to the basement membrane or the underlying dermis. At three days, the
      epidermis had healed and there was evidence of epidermal hyperplasia and
      hyperkeratosis that was completely resolved by 14 days. There were no infections
      and no scarring. Sham laser had no histomorphologic effects on the skin. There
      was no bacterial growth from all sham laser-treated wounds challenged with
      bacteria. Three of 20 (15%; 95% confidence interval = 0% to 31%) laser-irradiated
      wounds that were challenged with bacteria grew between 280,000 and 1,600,000
      colony-forming units/g. CONCLUSIONS: Laser irradiation results in ablation of the
      stratum corneum and a superficial burn to the epidermis that heals by three to 14
      days without any scarring or infection in pigs. Challenging laser-irradiated
      cutaneous wounds with a large bacterial inoculum resulted in bacterial growth in
      a minority of wounds.

PMID- 16293895
TI  - Factors associated with failure of noninvasive positive pressure ventilation in
      the emergency department.
AB  - OBJECTIVES: To determine the factors associated with failure of noninvasive
      positive pressure ventilation (NPPV) in patients presenting with acute
      respiratory failure to the emergency department (ED). METHODS: The authors
      retrospectively analyzed patients admitted to the ED for acute respiratory
      failure (defined as a PaCO2 level >45 mm Hg, and pH < or = 7.35 or a PaO2/FiO2
      ratio < 250 mm Hg) and who were treated with NPPV. NPPV was delivered routinely
      according to an institutional protocol. Failure of NPPV was defined as the
      requirement of endotracheal intubation at any time. RESULTS: A total of 104
      patients were included. NPPV failed in 31% (32/104), and the mortality was
      significantly higher in this group (12/32 [44%]) compared with patients who were
      not intubated (2/72 [3%]) (p < 0.0001). Factors associated with failure of NPPV
      were Glasgow Coma Scale score < 13 at ED admission (odds ratio [OR], 3.67; 95%
      confidence interval [CI] = 1.33 to 10.07), pH < or = 7.35 (OR, 3.23; 95% CI =
      1.25 to 8.31), and respiratory rate (RR) > or =20 min(-1) (OR, 3.86; 95% CI =
      1.33 to 11.17) after one hour of NPPV. The negative predictive value for NPPV
      failure was 86% (95% CI = 70% to 95%) for RR > or =20 min(-1). In the
      multivariate analysis, pH < or = 7.35 and RR > or =20 min(-1) after one hour of
      NPPV were independently associated with NPPV failure (adjusted ORs, 3.51; 95% CI
      = 1.29 to 9.62 and 3.55; 95% CI = 1.13 to 11.20, respectively). CONCLUSIONS:
      Patients with pH < or = 7.35 and an RR > or =20 min(-1) after one hour of NPPV
      had an increased risk of subsequent endotracheal intubation.

PMID- 16293896
TI  - Assessment of a new method to distinguish esophageal from tracheal intubation by
      measuring the endotracheal cuff pressure in a porcine model.
AB  - OBJECTIVES: With the knowledge of differences in anatomic structures between the
      trachea and the esophagus, the authors conducted an animal study to evaluate the
      usefulness of endotracheal cuff pressure in distinguishing endotracheal and
      esophageal intubations. METHODS: Six swine were anesthetized and endotracheally
      intubated with 7.5-mm cuffed endotracheal tubes. The intubations were confirmed
      by fiber-optic bronchoscopy. Each pilot balloon was connected to a 10-mL syringe
      and a manometer via a three-way stopcock. The cuff pressures were measured for
      each 1-mL incremental filling of air (1-10 mL). After removal of the endotracheal
      tubes, each swine was then intubated with the same endotracheal tubes into its
      esophagus. The cuff pressures of the esophageal intubation were measured with the
      same procedure. The cuff pressures and the pressure-volume relationships in both
      intubations were compared. RESULTS: The cuff pressure increased significantly in
      the esophageal intubation in comparison with the endotracheal intubation in all
      the comparisons from 1 mL to 10 mL (p = 0.028 for all Wilcoxon signed-rank
      tests). The slope of the pressure-volume curve of the cuff pressure was also
      significantly higher in the esophageal intubation during the inflation of the
      cuff on average (0.047 vs. 0.032 cm H2O/mL; p = 0.001), particularly in the first
      5 mL of air inflation. CONCLUSIONS: The cuff pressure in the esophageal
      intubation was significantly higher than that in the endotracheal intubation
      under the same inflated volume from 1 to 10 mL. This may provide the basis for an
      adjunctive, simple, rapid, and reliable method to verify endotracheal intubation.

PMID- 16293897
TI  - Changing opioid use for right lower quadrant abdominal pain in the emergency
      department.
AB  - OBJECTIVES: To compare the use of opioid analgesia in the treatment of emergency
      department patients with acute right lower quadrant (RLQ) abdominal pain between
      1998 and 2003 and to explore the relationship between opioid use and abdominal
      computed tomography (CT) scanning. METHODS: This was a retrospective cohort study
      of patients presenting in 1998 and 2003 to an urban emergency department with a
      triage complaint of RLQ pain. The authors abstracted use and timing of abdominal
      CT scanning and opioid analgesia. Other predictor variables were patient
      demographics. Risk ratio for receiving opioids with CT scan versus without CT
      scan, stratifying by year, were calculated. Proportional-hazards analysis was
      used to control for time in the emergency department. RESULTS: Of the 187
      patients seen in 1998, 38 (20%) underwent CT scanning and 43 (23%) received
      opioids. Of the 137 patients seen in 2003, 77 (56%) underwent CT scanning and 72
      (53%) received opioids. In 1998, the risk ratio for receiving opioids in patients
      who underwent CT scanning (vs. without) was 3.7 (95% confidence interval [CI] =
      2.3 to 6.1); in 2003, it was 1.5 (95% CI = 1.0 to 2.1). Opioids were
      overwhelmingly given before CT scanning in those patients who received both (81%
      in 1998 and 98% in 2003). The mean time to administration of the first opioid
      dose in 1998 was 155 minutes and in 2003 was 94 minutes. The proportional-hazards
      analysis confirmed a strong association between CT scanning and opioid
      administration in 1998 (relative hazard, 2.7; 95% CI = 1.5 to 5.1) and
      substantial attenuation of the association in 2003 (relative hazard, 1.3; 95% CI
      = 0.8 to 2.1). The hospitalization rate was not significantly different in 2003
      (33%) versus 1998 (27%) (p = 0.28). The risk ratio of receiving opioids in
      admitted patients was 2.8 (95% CI = 1.7 to 4.6) in 1998 and 2.0 (95% CI = 1.5 to
      2.7) in 2003. CONCLUSIONS: Opioid administration to patients with RLQ pain has
      dramatically increased between 1998 and 2003. During these five years, the number
      of patients receiving opioids more than doubled and the time to first
      administration of opioids decreased by one hour. The authors show that this
      cannot be attributed to an increased use of CT scanning.

PMID- 16293898
TI  - Resident efficiency in a pediatric emergency department.
AB  - OBJECTIVES: To measure the hourly rate of patients evaluated and treated by
      resident physicians in an academic pediatric emergency department (PED) and
      examine differences in the rate by subspecialty and year of training. METHODS:
      For all residents rotating in an academic, urban children's hospital PED, the
      rate of patients seen per hour over the course of their rotation was calculated
      using an electronic tracking system, EmSTAT, for calendar year 2000. Rates are
      reported as the mean number of patients seen per resident hour worked. Mean
      differences are reported for resident subspecialties (emergency medicine,
      pediatrics, and family practice) and postgraduate year (PGY1-PGY3), and subclass
      comparisons were made with an analysis of variance test with Tukey's post hoc
      analysis. RESULTS: A total of 153 residents (63.4% pediatric, 18.9% family
      practice, and 17.7% emergency medicine) saw 24,414 patients during the study
      period. The makeup of the group by training year was as follows: PGY1, 20.9%;
      PGY2, 41.2%; and PGY3, 37.9%. For all residents, the mean rate was 1.02 patients
      seen per hour (pph). Significant differences in the mean number of patients seen
      per hour by subspecialty existed, with emergency medicine residents seeing a mean
      of 1.12 pph, pediatrics residents seeing 1.02 pph, and family practice residents
      seeing 0.93 pph (mean difference, p < 0.05 for all comparisons). Rates increased
      by year of training, with PGY1 seeing a mean of 0.95 pph, PGY2 seeing 0.99 pph,
      and PGY3 seeing 1.09 pph (mean difference, p < 0.05 for all comparisons except
      PGY1 vs. PGY2). CONCLUSIONS: Significant differences in the rate of patients
      evaluated and treated in the PED exist by resident subspecialty and year of
      training. Knowing these rates is helpful in evaluation of resident performance,
      because it allows comparison with peers. Additionally, such information may be
      useful for residency program evaluators to gauge the amount of patient exposure
      for residents.

PMID- 16293899
TI  - Identification of depression in an inner-city population using a simple screen.
AB  - OBJECTIVES: The purpose of this study was to compare a brief screening tool with
      physicians' usual practice in detecting depressive symptoms in patients
      presenting with somatic complaints to an inner-city emergency department.
      Depression is a major cause of morbidity and mortality in the United States.
      Underprivileged patients who rely on emergency departments for primary care
      remain at risk for undetected depression. METHODS: This prospective observational
      study included all patients older than 18 years presenting to an urgent care
      clinic staffed by emergency physicians in an urban public hospital during an
      eight-week period. Clinically unstable patients and those with a chief complaint
      of depression were excluded. After consenting, patients completed a previously
      validated two-question screening tool for depression. Patients identified as
      having depressive symptoms were referred to social workers for evaluation for
      possible psychiatric intervention. RESULTS: Of the 226 patients enrolled, 55%
      (124/226; 95% confidence interval [CI] = 48% to 61%) screened positive for
      depressive symptoms. Physicians identified 14% (31/226; 95% CI = 10% to 19%) as
      having depressive symptoms. The kappa value was 0.22 (95% CI = 0.14 to 0.29). All
      patients but one identified as positive by the physicians screened positive on
      the screening tool. Patients who screened positive were referred to social
      workers. The physicians failed to identify 19 of the patients who needed further
      psychiatric care. CONCLUSIONS: Depressive symptoms are common among patients in
      urgent care settings with somatic complaints. A simple screening tool identified
      more patients for further evaluation than does physicians' usual practice.

PMID- 16293900
TI  - The influence of the self-contained breathing apparatus (SCBA) on ventilatory
      function and maximal exercise.
AB  - Our previous work showed that breathing low density gases during exercise with
      the self-contained breathing apparatus (SCBA) improves maximal ventilation (V(E))
      and maximal oxygen consumption (VO(2)max). This suggests that the SCBA limits
      exercise by adding a resistive load to breathing. In this study we compared
      VO(2)max with and without the various components comprising the SCBA to determine
      their impact on VO(2)max. Twelve males performed 4 randomly ordered incremental
      exercise tests to exhaustion on a treadmill: (1) low-resistance breathing valve
      only (CON); (2) full SCBA (SCBA); (3) SCBA regulator only (REG); and (4) carrying
      the cylinder and harness assembly but breathing through a low-resistance
      breathing valve (PACK). Compared to CON, VO(2)max was reduced to a similar extent
      in the SCBA and REG trials (14.9% and 13.1%, respectively). The PACK condition
      also reduced VO(2)max, but to a lesser extent (4.8 +/- 5.3%). At VO(2)max, VE was
      decreased and expiratory mouth pressure and external breathing resistance (BR)
      were increased in both the SCBA and REG trials. There was a significant
      correlation between the change in maximal V(E)and VO(2)max with the SCBA. The
      results show that the SCBA reduces VO(2)max by limiting V(E) secondary to the
      increased BR of the SCBA regulator.

PMID- 16293901
TI  - Effect of endurance training on different mechanical efficiency indices during
      submaximal cycling in subjects unaccustomed to cycling.
AB  - The purpose of this study was to evaluate different efficiency indices, i.e.,
      gross (GE: no baseline correction), net (NE: resting metabolism as baseline
      correction), and work (WE: unloaded exercise as baseline correction), to reveal
      the effect of endurance training on mechanical efficiency. Nine healthy sedentary
      women undertook an incremental test and submaximal cycling exercise, at an
      intensity corresponding to 50% of the pretraining peak oxygen uptake, before and
      after 6 weeks of endurance training (18 sessions of 45 min). The training effects
      on efficiency indices were tested by comparisons based on GE, NE, and WE as well
      as by the differences between the percentage changes of all indices (%GE, %NE,
      %WE). Endurance training resulted in significantly higher GE (+11.1%; p < 0.001)
      and NE (+9.1%; p < 0.01). Only minor significant improvement (+2.4%; p < 0.05)
      was observed with the WE index because the value used for baseline subtraction
      was significantly reduced by the training sessions, due perhaps to improvement in
      pedaling skill. As a consequence, %WE was significantly lower than %GE (p < 0.01)
      and %NE (p < 0.05), while %GE and %NE were not significantly different. We
      conclude that mechanical efficiency of cycling increases with training in women
      previously unfamiliar with cycling, and that the WE index is less sensitive to
      this training effect than GE and NE indices.

PMID- 16293902
TI  - Attenuation of protective effect against eccentric exercise-induced muscle
      damage.
AB  - A single bout of eccentric exercise confers a long-lasting protective effect
      against subsequent bouts of the same exercise. This study investigated how the
      protective effect was lessened when the interval between the initial and
      secondary exercise bouts was increased from 4 to 12 weeks. Thirty young men
      performed two bouts of 12 maximal eccentric actions of the elbow flexors of the
      nondominant arm separated by either 4 (n = 9), 8 (n = 10), or 12 (n = 11) weeks.
      Maximal isometric strength, flexed and relaxed elbow joint angles, range of
      motion, upper arm circumference, muscle soreness, plasma creatine kinase (CK),
      and myoglobin (Mb) were measured before, immediately after, and for 4 days after
      exercise. Changes in criterion measures were compared between bouts for each
      group and among groups by two-way repeated-measures ANOVA. There were no
      significant differences among groups in the changes in all measures following the
      first bout. Significantly (p < 0.05) smaller responses in all measures were
      observed after the second bout as compared with first bout for the 4 and 8 weeks,
      but only in strength, muscle soreness, CK, and Mb for the 12 weeks. It was
      concluded that some aspects of the protective effect were attenuated after 8
      weeks, and the factors responsible for the effect vary among the measures.

PMID- 16293903
TI  - VO2 responses to intermittent swimming sets at velocity associated with VO2max.
AB  - While the physiological adaptations following endurance training are relatively
      well understood, in swimming there is a dearth of knowledge regarding the
      metabolic responses to interval training (IT). The hypothesis tested predicted
      that two different endurance swimming IT sets would induce differences in the
      total time the subjects swam at a high percentage of maximal oxygen consumption
      (VO(2)max). Ten trained triathletes underwent an incremental test to exhaustion
      in swimming so that the swimming velocity associated with VO(2)max (vVO(2)max)
      could be determined. This was followed by a maximal 400-m test and two
      intermittent sets at vVO(2)max: (a) 16 x 50 m with 15-s rest (IT(50)); (b) 8 x
      100 m with 30-s rest (IT(100)). The times sustained above 95% VO(2)max (68.50 +/-
      62.69 vs. 145.01 +/- 165.91 sec) and 95% HRmax (146.67 +/- 131.99 vs. 169.78 +/-
      203.45 sec, p = 0.54) did not differ between IT(50) and IT(100)(values are mean
      +/- SD). In conclusion, swimming IT sets of equal time duration at vVO(2)max but
      of differing work-interval durations led to slightly different VO(2)and HR
      responses. The time spent above 95% of VO(2)max was twice as long in IT(100) as
      in IT (50), and a large variability between mean VO(2)and HR values was also
      observed.

PMID- 16293904
TI  - Blood flow to exercising limbs varies with age, gender, and training status.
AB  - Understanding the effects of physiological aging on blood flow to active skeletal
      muscle and its regulation during exercise has important functional, hemodynamic,
      and metabolic implications for our rapidly expanding elderly population. During
      peak exercise involving a large muscle mass, blood flow to the legs is lower in
      healthy older compared to younger persons; this results from central (reduced
      cardiac output) and peripheral (reduced leg vascular conductance) limitations.
      There is considerable variability in the literature concerning age-related
      changes in leg blood flow during submaximal exercise, with reports of similar or
      reduced leg blood flow and vascular conductance in older vs. younger subjects
      depending on the exercise intensity and the gender and training status of the
      subjects. However, all the studies involving non-endurance-trained subjects are
      consistent in that older subjects achieve the requisite leg blood flow at higher
      arterial perfusion pressures than young subjects, suggesting altered local
      vasoregulatory mechanisms with aging. Although the nature of these age-related
      alterations is poorly understood, we have preliminary evidence for augmented
      sympathetic vasoconstrictor responsiveness in the legs of older men during
      exercise, and blunted leg vasodilator responsiveness in older women. Systematic
      research will be needed in order to define the central and local mechanisms
      underlying these age- and gender-specific differences in muscle vascular
      responsiveness. Such information will be important for designing future
      interventions aimed at improving muscle blood supply and functional capacity in
      older persons.

PMID- 16293905
TI  - The versatility of the pump-perfused rat hindlimb preparation: examples relating
      to skeletal muscle function and energy metabolism.
AB  - The pump-perfused rat hindlimb model, in various forms, has been in use for
      several decades. There are many applications for this model, owing to the ability
      to control the content and rate of perfusion. In the context of exercise
      physiology this model has been put to particularly good use. In this report we
      summarize some of the central surgical differences between different versions of
      the pump-perfused rat hindlimb model, including the double hindlimb + trunk,
      double hindlimb alone, single hindlimb, and distal hindlimb-alone models. We also
      summarize specific elements of the perfusion medium and measurement of force used
      in our lab during assessment of muscle metabolic and contractile responses, and
      illustrate some of the differences from the in vivo condition that merit
      consideration. We then provide specific examples of how the single pump-perfused
      hindlimb and distal hindlimb-alone versions of this model have been used to study
      muscle function and energy metabolism. In this context we show how this model can
      be used to permit the experimenter to manipulate and control the rate of
      O(2)delivery and to add specific compounds that inhibit a particular aspect of
      muscle metabolism, such that in combination with measurements of the flux of
      specific substances across the muscle and/or fast-freezing of muscle after
      contractions, more can be understood about the metabolic state of the contracting
      muscles.

PMID- 16293906
TI  - Muscle hypertrophy models: applications for research on aging.
AB  - Muscle hypertrophy is an adaptive response to overload that requires increasing
      gene transcription and synthesis of muscle-specific proteins resulting in
      increased protein accumulation. Progressive resistance training (P(RT)) is
      thought to be among the best means for achieving hypertrophy in humans. However,
      hypertrophy and functional adaptations to P(RT) in the muscles of humans are
      often difficult to evaluate because adaptations can take weeks, months, or even
      years before they become evident, and there is a large variability in response to
      P(RT) among humans. In contrast, various animal models have been developed which
      quickly result in extensive muscle hypertrophy. Several such models allow precise
      control of the loading parameters and records of muscle activation and
      performance throughout overload. Scientists using animal models of muscle
      hypertrophy should be familiar with the advantages and disadvantages of each and
      thereby choose the model that best addresses their research question. The
      purposes of this paper are to review animal models currently being used in basic
      research laboratories, discuss the hypertrophic and functional outcomes as well
      as applications of these models to aging, and highlight a few mechanisms involved
      in regulating hypertrophy as a result of applying these animal models to
      questions in research on aging.

PMID- 16293907
TI  - Application of animal models: chronic electrical stimulation-induced contractile
      activity.
AB  - Unilateral, chronic low-frequency electrical stimulation (CLFS) is an
      experimental model that evokes numerous biochemical and physiological adaptations
      in skeletal muscle. These occur within a short time frame and are restricted to
      the stimulated muscle. The humoral effects of whole body exercise are eliminated
      and the nonstimulated contralateral limb can often be used as a control muscle,
      if possible effects on the contralateral side are considered. CLFS induces a fast
      to-slow transformation of muscle because of alterations in calcium dynamics and
      myofibrillar proteins, and a white-to-red transformation because of changes in
      mitochondrial enzymes, myoglobin, and the induction of angiogenesis. These
      adaptations occur in a coordinated time-dependent manner and result from altered
      gene expression, including transcriptional and posttranscriptional processes.
      CLFS techniques have also been applied to myocytes in cell culture, which provide
      a greater opportunity for the delivery of pharmacological agents or for the
      application of gene transfer methodologies. Clinical applications of the CLFS
      technique have been limited, but they have shown potential therapeutic value in
      patients in whom voluntary muscle contraction is not possible due to debilitating
      disease and/or injury. Thus the CLFS technique has great value for studying
      various aspects of muscle adaptation, and its wider scientific application to a
      variety of neuromuscular-based disorders in humans appears to be warranted.

PMID- 16293908
TI  - Impact of metabolic syndrome as a risk factor for atherothrombotic stroke.

PMID- 16293910
TI  - Thrombocytosis in iron deficiency anemia.

PMID- 16293909
TI  - Is "acute hepatitis-like onset" a hither-to poorly recognized clinical
      manifestation of primary biliary cirrhosis at an early stage ?

PMID- 16293911
TI  - New classification and treatment for myotonic disorders.
AB  - Myotonia is repetitive firing of muscle action potentials causing prolonged
      muscle contractions even after mechanical stimulations to the muscles have
      ceased. Most common myotonic disorder is myotonic dystrophy which is now termed
      DM1, myotonic dystrophy type 1. In Japan, proximal myotonic myopathy, which is
      now called DM2 has not been reported. Both DM1 and DM2 have Cl channel
      abnormality which causes myotonia. Less commonly we encounter Thomsen's disease,
      and autosomal recessive generalized myotonia (Becker type) which also have a Cl
      channel abnormality. There are other myotonic disorders related to Na
      channelopathy which include three disorders: paramyotonia congenita, adynamia
      episodica hereditaria, and myotonia fluctuans. Myotonia has been treated by
      various Na channel blockers, mexiletine, phenytoin, and carbamazepine, but they
      were originally developed for cardiac arrhythmia, or seizure disorders and they
      have undesirable side effects, weakness. Comprehensive treatment includes
      myotonia control without reducing the strength, and care for systemic
      manifestations of DM1.

PMID- 16293912
TI  - Treatment of elderly patients with early gastric cancer by endoscopic submucosal
      dissection using an insulated-tip diathermic knife.
AB  - OBJECTIVE: In recent years, the number of elderly patients with early gastric
      cancer (EGC) has steadily been increasing. In our institute, endoscopic
      submucosal dissection (ESD) involving the use of an insulated-tip diathermic
      knife (IT-ESD) was introduced for the treatment of mucosal gastric carcinoma in
      1996. The purpose of this study was to evaluate the effectiveness of IT-ESD for
      the treatment of elderly patients with EGC. MATERIALS AND METHODS: A total of 144
      patients with EGC were treated at Shikoku Cancer Center in the 5-year period from
      January 2000 to December 2004, including 53 patients over 75 years old. The
      performance status (PS) for all patients was less than 2. We compared patient's
      backgrounds, the one-piece resection rate, complete resection (CR) rate,
      operation time, bleeding rate, perforation rate, blood pressure, and peripheral
      oxygen saturation (SpO(2)) between patients over 75 years of age (elderly group)
      and the remaining 91 younger patients (non-elderly group). RESULTS: The rate of
      having underlying disease was significantly higher for the elderly group (p<0.05)
      and we found no significant difference for the one-piece resection rate, CR rate,
      operation time, bleeding rate, and perforation rate between the 2 groups. There
      were also no significant differences for the frequency of the use of oxygen,
      pressor and depressor between the 2 groups. CONCLUSION: There was no significant
      difference in the outcome resulting from ESD between the 2 groups. Our study
      proves that ESD is a feasible treatment for elderly patients with EGC PS of less
      than 2.

PMID- 16293913
TI  - Relationship between heart-type fatty acid-binding protein levels and the risk of
      death in patients with serious condition on arrival at the emergency department.
AB  - OBJECTIVE: Although heart-type fatty acid-binding protein (H-FABP) is a cardiac
      marker useful for early diagnosis of acute myocardial infarction (AMI), few data
      are available on its prognostic value. The objective of this study is to clarify
      the prognostic value of H-FABP in patients with a serious condition. METHODS AND
      PATIENTS: We conducted a prospective study of 617 patients who presented to the
      emergency department with a serious condition. The H-FABP levels on arrival at
      the emergency department were divided into four groups using their quartiles. The
      endpoint was death from any causes in-hospital. RESULTS: H-FABP ranged from 1.2
      to 2,300 ng/ml, with a median of 19.9 ng/ml, a 25%-value of 6.7 ng/ml and 75%
      value of 54.0 ng/ml. The unadjusted rate of the mortality increased progressively
      with increasing H-FABP quartile point (11% for quartile-I, 22% for quartile-II,
      36% for quartile-III, and 38% for quartile-IV; p<0.001). After adjustment for
      age, gender, systolic blood pressure and the presence or absence of
      cardiovascular disease, H-FABP was the independent factor to predict the
      mortality. CONCLUSION: H-FABP has proven to be an independent factor for
      prognosis in patients with a serious condition on arrival at the emergency
      department.

PMID- 16293914
TI  - N-isopropyl-p- 123I iodoamphetamine single photon emission computed tomography
      study of Parkinson's disease with dementia.
AB  - BACKGROUND: Intellectual deterioration occurs in 10-40% of patients with
      Parkinson's disease. However, there are many conflicting studies on its relation
      with brain perfusion and the nature of this dementing process remains
      controversial. OBJECTIVE: To compare cortical perfusion by SPECT using (123)I-IMP
      between Parkinson's disease patients with dementia and those without dementia and
      to investigate the correlation between dementia in Parkinson's disease and brain
      perfusion in various areas. METHODS: Fifty-two cases of Parkinson's disease and
      10 control cases were studied. The Parkinson's disease with dementia group
      included 30 cases and the Parkinson's disease without dementia group included 22
      cases. RESULTS: By multiple logistic regression method, we demonstrated
      significant hypoperfusion in the occipital cortex in Parkinson's disease with
      dementia. CONCLUSIONS: The cause of dementia in Parkinson's disease may vary. We
      demonstrated that occipital hypoperfusion was closely correlated to dementia in
      Parkinson's disease compared to frontal, parietal and temporal perfusion.

PMID- 16293915
TI  - Rapid-onset primary biliary cirrhosis resembling drug-induced liver injury.
AB  - A 54-year-old woman was admitted to our hospital because of acute liver injury.
      Since she had a history of having used a diet product, drug-induced liver injury
      (DILI) was initially considered. However, the patient was subsequently diagnosed
      as suffering from primary biliary cirrhosis (PBC) based on the findings of liver
      histology and serum anti-mitochondrial antibody positivity. Overlap syndrome
      between PBC and autoimmune hepatitis (AIH) was also suspected, however, serum
      levels of aspartate aminotransferase, alanine aminotransferase and alkaline
      phosphatase became normal three months later, after treatment with combination
      therapy comprising ursodeoxycholic acid plus bezafibrate. We therefore concluded
      that the liver disease in this patient was actually PBC, but that it resembled
      overlap syndrome or DILI. In cases of PBC, a rapid onset, as frequently seen in
      the case of DILI, viral hepatitis or AIH, is not common. We herein report a rare
      case of PBC which resembled DILI.

PMID- 16293916
TI  - Infective tricuspid valve endocarditis with pulmonary emboli caused by
      Campylobacter fetus after tooth extraction.
AB  - We describe a case of infective endocarditis caused by Campylobacter fetus
      accompanied by pulmonary emboli. A 52-year-old man was referred to our hospital
      due to febrile temperatures with a history of dental treatment followed by eating
      raw meat. Computed tomography revealed multiple infiltrations and a nodule with
      low attenuation area and feeding vessels. A mobile mass, possible vegetation,
      attached to the tricuspid valve was detected by transthoracic echocardiography.
      Two blood cultures disclosed Campylobacter fetus. Long-term antibiotic therapy
      was given, curing the infection with valvuloplasty. We presented the possibility
      that infective Campylobacter fetus endocarditis after dental treatment was caused
      by eating raw meat.

PMID- 16293917
TI  - Cholesterol embolism after cardiac catheterization mimicking infective
      endocarditis.
AB  - We present a 65-year-old man with rheumatic combined valvular heart disease
      showing persistent fever 3 weeks after diagnostic cardiac catheterization.
      Infective endocarditis was strongly suspected from the clinical course, however,
      serial blood cultures were negative. Transesophageal echocardiography, done to
      investigate vegetation, revealed multiple mobile plaques in the descending aorta.
      Administration of both steroid and simvastatin improved both symptoms and renal
      function. Cholesterol embolism should be considered to be one of the possible
      causes of low-grade fever after cardiac catheterization especially in patients
      with anticoagulation.

PMID- 16293918
TI  - A patient with Graves' disease accompanied by bloody pericardial effusion.
AB  - A hyperthyroid patient with bloody pericardial effusion is presented. He was
      hospitalized for severe dyspnea. Pericardiocentesis yielded 1.2 liters of bloody
      fluid. Biochemical, cytologic, and radiologic examinations failed to identify the
      etiology of the effusion. Upon normalization of thyroid function using
      antithyroid drugs, the pericardial effusion resolved without recurrence. The
      patient was diagnosed as Graves' disease, which rarely is complicated by bloody
      pericardial effusion. As it is rarely reported and not widely known, this
      association may be underdiagnosed.

PMID- 16293919
TI  - Cat-eye syndrome with isolated idiopathic hypogonadotropic hypogonadism.
AB  - A 34-year-old Japanese man diagnosed as having cat-eye syndrome (CES) with
      isolated idiopathic hypogonadotropic hypogonadism (IHH) was treated at our
      university. He showed preauricular pits/tags, downward slanting palpebral
      fissures, ocular hypertelorism, and strabismus. However, ocular coloboma and anal
      atresia, major characteristic features of CES, were negative. Chromosomal
      analysis revealed malformation in chromosome 22 and eunuchoid features and a low
      grade development of secondary sexual characteristics were also evident.
      Endocrinological examinations revealed that this patient was in a state of
      isolated IHH. Although CES with IHH is extremely rare, endocrine disorders should
      be given due attention.

PMID- 16293920
TI  - Acute renal failure likely due to acute nephritic syndrome associated with
      typhoid fever.
AB  - A 45-year-old woman was admitted to our hospital because of high fever and
      malaise. She also presented abnormal urine findings including macrohematuria and
      proteinuria with transient renal insufficiency. Salmonella Typhi was isolated
      from her blood and stool culture, and then she was diagnosed as having typhoid
      fever. Salmonella enterica serotype typhi infection can be complicated by renal
      involvement, although rare. In Japan, few cases have been reported about acute
      nephritic syndrome in typhoid fever. Here, we report a case of endemic acquired
      typhoid fever associated with acute renal failure probably due to acute nephritic
      syndrome successfully treated with levofloxacin.

PMID- 16293921
TI  - Diabetes mellitus complicated with rapidly progressive glomerulonephritis in an
      elderly patient.
AB  - An 88-year-old man with a 30-year history of type 2 diabetes and a 3-year history
      of chronic renal failure was admitted for evaluation of anasarca. On admission,
      findings of nephrotic syndrome and microscopic hematuria were observed. During
      the course of therapy, rapid deterioration of renal function occurred with the
      appearance of pneumonia. Irrespective of the therapy with hemodialysis and
      antibiotics, he died of respiratory failure. The autopsy showed a rare case of
      rapidly progressive glomerulonephritis (crescentic glomerulonephritis)
      superimposed on membranous nephropathy. This experience highlighted the
      importance of the differential diagnosis of non-diabetic glomerulopathy even in
      elderly patients with diabetes mellitus.

PMID- 16293922
TI  - Acute multifocal bacterial nephritis complicated with acute renal failure and
      thrombocytopenia.
AB  - A 50-year-old woman was transferred to our hospital because of acute renal
      failure and thrombocytopenia. Due to rapid enlargement of the kidney, we first
      suspected that she had diffuse renal invasion of anaplastic carcinoma or lymphoma
      of the kidney. Anti-bacterial treatment for complicated urinary tract infection
      and hemodialysis treatment resulted in recovery of both renal function and
      thrombocytopenia. Serial CT study demonstrated disappearance of kidney swelling
      and multiple masses within the kidney. We finally made a diagnosis of acute
      multifocal bacterial nephritis. Timely initiation of dialysis therapy and
      appropriate anti-bacterial treatment was essential to rescue this case.

PMID- 16293923
TI  - Anaphylaxis to aprotinin in fibrin sealant.
AB  - A 50-year-old man with chronic otitis media was admitted to our hospital for
      investigation of lung cancer. He had received repeated instillations of fibrin
      sealant (Bolheal) in myringoplasty 7 times over 12 months. During the lower
      lobectomy, soon after fibrin sealant was applied to seal bronchopleural fistulas,
      systolic blood pressure decreased to 60 mmHg. Treatment with epinephrine and
      dopamine was required until his condition improved 2 days later. The specific IgE
      antibody was detected for the solution for fibrinogen and factor XIII containing
      bovine aprotinin. Cross-reactivity between purified aprotinin and the solution
      was noted by competitive ELISA inhibition tests.

PMID- 16293924
TI  - Iron deficiency anemia with marked thrombocytosis complicated by central retinal
      vein occlusion.
AB  - We report a case of severe iron deficiency anemia with marked thrombocytosis that
      was complicated by central retinal vein occlusion. Platelet count was over one
      million per microliter and an increased number of megakaryocytes was observed in
      the bone marrow at the time of diagnosis of iron deficiency anemia, features that
      resemble those of essential thrombocythemia. However, the platelet count rapidly
      declined with the administration of ferrous fumarate. Accordingly, central
      retinal vein occlusion was improved and has not recurred. In this case,
      significant thrombocytosis caused by iron deficiency anemia may have been
      involved in the development of central retinal vein occlusion.

PMID- 16293925
TI  - Leukemoid reaction in association with bone marrow necrosis due to metastatic
      prostate cancer.
AB  - An 80-year-old man presented to the internist with fever, fatigue and
      leukocytosis up to 66.8 x 10(3)/microl. Although a chronic myelogenous leukemia
      was initially suspected, he was diagnosed as metastatic bone marrow tumor with
      bone marrow necrosis from primary prostate cancer on the basis of the clinical
      and pathological findings. The serum concentrations of IL-6 and TNF-alpha were
      mildly elevated to 65.0 pg/ml and, 54.0 pg/ml respectively. It is probable that
      these humoral factors were partially responsible for the leukemoid reaction
      although other factors induced by the bone marrow necrosis with bone marrow
      metastasis of prostate cancer are also likely involved.

PMID- 16293926
TI  - Hypersensitivity to mosquito bites as a potential sign of mantle cell lymphoma.
AB  - Hypersensitivity to mosquito bites (HMB) is known to be an allergic reaction and
      also a skin symptom in some cases of natural killer cell leukemia/lymphoma
      associated with Epstein-Barr virus (EBV) infection. We describe a patient who had
      suffered from HMB for 5 years, and subsequently developed mantle cell lymphoma
      (MCL), which resembled chronic lymphocytic leukemia in the early phase. EBV
      monoclonality was not detected in lymph nodes by Southern blotting. Serum levels
      of interleukin-4 and IgE were increased, but they decreased and HMB disappeared
      when MCL was predominant. We consider that HMB may be a potential sign of MCL.

PMID- 16293927
TI  - Septic intramuscular embolism in a neutropenic patient with myelodysplastic
      syndrome accompanied by asymptomatic septic pulmonary emboli.
AB  - Septic embolisms are rare disorders which are associated with increased mortality
      and morbidity. We describe a rare case of septic intramuscular embolism
      accompanied by asymptomatic pulmonary embolism in a neutropenic patient.
      Methicillin-sensitive Staphylococcus aureus (S. aureus) was detected and multiple
      nodules were revealed in both thighs and lung. Although he was treated with
      sensitive antibiotics to .S. aureus, the symptoms remained unchanged during the
      neutropenic period. Fever subsided rapidly and his thigh pain disappeared after
      neutropenia resolved. A prompt diagnosis and optimal therapeutic decisions are
      critical for the reduction of mortality.

PMID- 16293928
TI  - Living-donor lobar lung transplantation in Sauropus androgynus-associated
      bronchiolitis obliterans in Japan.

PMID- 16293929
TI  - Intimal flap of ascending aortic dissection with valve-like motion diagnosed by
      transesophageal echocardiography.

PMID- 16293930
TI  - Infective aortitis.

PMID- 16293931
TI  - Myocardial metastasis from primary lung cancer.

PMID- 16293932
TI  - Successful treatment of cervical spinal epidural abscess without surgery.

PMID- 16293933
TI  - Ossification of the yellow ligament in thoracic spine.

PMID- 16293934
TI  - Protein-losing enteropathy associated with immune complex-mediated vasculopathy
      in a case of undifferentiated connective tissue disease.

PMID- 16293935
TI  - Pathophysiological significance of T-type Ca2+ channels: T-type Ca2+ channels and
      drug development.
AB  - T-type Ca(2+) channels are present in cardiovascular, neuronal, and endocrine
      systems; and they are now receiving attention as novel therapeutic targets. Many
      drugs and compounds non-specificaly block T-type Ca(2+) channels. Certain
      dihydropyridine compounds, such as efonidipine, have blocking activity on both L
      type and T-type Ca(2+) channels which possibly underlies their excellent clinical
      profiles such as minimum reflex tachycardia and renal protection. Selective
      inhibitors of T-type Ca(2+) channels, such as non-hydrolyzable mibefradil and R(
      )-efonidipine, are powerful pharmacological tools for further studies and may
      lead to the development of novel therapeutic strategies.

PMID- 16293936
TI  - Pathophysiological significance of T-type Ca2+ channels: role of T-type Ca2+
      channels in renal microcirculation.
AB  - Since conventional Ca(2+) antagonists, with predominant blockade of L-type
      voltage-dependent Ca(2+) channels, elicit preferential dilation of afferent
      arterioles, they might ostensibly aggravate glomerular hypertension. Recently,
      novel Ca(2+) antagonists, with inhibitory action on L-/T-type Ca(2+) channels,
      have been reported to dilate both afferent and efferent arterioles. The present
      review attempted to characterize the renal action of these Ca(2+) antagonists and
      evaluated the consequences following the treatment with these agents. In contrast
      to conventional Ca(2+) antagonists (e.g., nifedipine), novel antagonists (e.g.,
      benidipine, efonidipine) potently dilated afferent and efferent arterioles; their
      action on efferent arterioles appeared to be mediated by the T-type Ca(2+)
      channel blockade, probably through the inhibition of the intracellular Ca(2+)
      release. The comparison of the anti-proteinuric action in subtotally
      nephrectomized rats showed that efonidipine exerted more prominent action than
      nifedipine. Furthermore, Ca(2+) antagonists with T-type Ca(2+) inhibitory action
      inhibited renin/aldosterone release and proinflammatory process. Finally,
      patients with chronic renal disease given a 48-week efonidipine treatment showed
      reduced proteinuria, and this effect was seen even when mean arterial blood
      pressure failed to become less than 100 mmHg. Collectively, T-type Ca(2+) channel
      blockade provides beneficial action in renal injury. Various mechanisms serve to
      protect against renal injury, including systemic/glomerular hemodynamic action
      and non-hemodynamic mechanisms.

PMID- 16293938
TI  - Development of pig embryos after electro-activation and in vitro fertilization in
      PZM-3 or PZM supplemented with fetal bovine serum.
AB  - The aim of present study was to optimize culture conditions for pig embryos.
      Initially, we evaluated three different basic culture conditions. When embryos
      from electro-activation (parthenotes) or in vitro fertilization (IVF-embryos)
      were cultured in PZM supplemented with 3 mg/ml bovine serum albumin (PZM-3) in 4
      well dishes, in medium covered with oil in 4-well dishes or in droplets under
      oil, 0%, 33% and 20% of the parthenotes, and 11%, 23% and 20% of the IVF-embryos
      developed to blastocysts. Subsequently, we examined the development of embryos
      when they were cultured in 4-well dishes in medium covered with oil continuously
      for 7 days or cultured under the same conditions but with a change to fresh
      medium on Days 2 and 4. In this experiment, 23% (no medium change) and 34%
      (change) of the parthenotes developed to blastocysts, respectively. When IVF
      embryos were cultured under similar conditions, 33% and 38% of the embryos
      developed to blastocysts. Further improvement was achieved when PZM was
      supplemented with FBS from Day 4. In this experiment, 47% of the parthenotes
      developed to blastocysts with an average cell number of 57 +/- 7.7. In IVF-embryo
      group, 49% of the embryos developed to blastocysts with a mean cell number of 60
      +/- 6.1. These results indicate that a change to fresh medium and inclusion of
      FBS in the medium during the late stages of culture can generate a higher
      proportion of high-quality blastocysts.

PMID- 16293937
TI  - Comparative effects of indomethacin and nabumetone on urine and electrolyte
      output in conscious rats.
AB  - The effects of indomethacin and nabumetone on urine and electrolyte excretion in
      conscious rats were examined. Male Sprague-Dawley rats were housed individually
      for a five-week duration, consisting of acclimatization, control, experimental,
      and recovery phases. During the experimental phase, rats were given either
      indomethacin (1.5 mg . kg(-1) body weight . day(-1) in 0.5 ml saline, n = 10),
      nabumetone (15 mg . kg(-1) body weight . day(-1) 0.5 ml saline, n = 10), or 0.5
      ml saline alone (n = 10) for a period of two weeks. Water and food intake, body
      weight, urine output, and electrolyte excretions were estimated. Data were
      analyzed using two-way ANOVA. Urine output in the indomethacin- and nabumetone
      treated groups was not different from the controls, but was significantly
      different between the drug-treated groups (P<0.01). Sodium, potassium, calcium,
      and magnesium excretions were not different between nabumetone-treated and
      control rats. However, sodium and potassium excretion was significantly lower in
      rats receiving indomethacin when compared to the control rats. Calcium and
      magnesium outputs, although did not differ from the controls, nevertheless
      decreased significantly with indomethacin (P<0.01). It appears that indomethacin
      and nabumetone when given at maximum human therapeutic doses may affect urine and
      electrolyte output in conscious rats.

PMID- 16293940
TI  - Stage specific expression of histone deacetylase 4 (HDAC4) during oogenesis and
      early preimplantation development in mice.
AB  - Oogenesis is a critical event in the formation of gametes, which transfer genomic
      information to the next generation. During this process, the gene expression
      pattern changes dramatically concomitant with genome remodeling, while the
      genomic information is stably maintained. Histone acetylation, the level of which
      is dramatically changed during oogenesis, has been implicated in the regulation
      of genome remodeling. In order to identify genes that are involved in the dynamic
      changes in histone acetylation levels during oogenesis, we performed suppressive
      subtraction hybridization (SSH) using unfertilized versus fertilized oocytes.
      Among the genes identified by SSH, we found histone deacetylase 4 (HDAC4), whose
      expression has been detected in only a few types of adult tissues. RT-PCR
      analysis revealed that the expression of HDAC4 was specific for full-grown
      oocytes. The HDAC4 transcript was barely detected in the growing oocytes, whereas
      it was readily detectable in fully grown oocytes. The expression was maintained
      at a high level until the MII stage, but decreased prominently after
      fertilization. Then, the expression level remained low until the morula stage.
      Immunocytochemistry localized the HDAC4 protein in the chromosome of fully grown
      oocytes. Although HDACs are most closely linked with transcriptional regulation
      owing to deacetylation of the core histones of the chromatin, previous studies
      have shown that all of the histone residues examined were highly acetylated in
      full-grown oocytes. Therefore, our results suggest that HDAC4 acts on a non
      histone protein and plays a role in some other cellular functions of full-grown
      oocytes. To address this possibility, we examined the expression of p53BP1, which
      is associated with HDAC4 and plays a critical role in the DNA damage response. RT
      PCR analysis revealed that p53BP1 was expressed specifically in fully grown
      oocytes, as was HDAC4. These results suggest that HDAC4 plays a role in
      stabilizing the genomes of fully grown oocytes.

PMID- 16293939
TI  - The effect of active immunization against inhibin on gonadotropin secretions and
      follicular dynamics during the estrous cycle in cows.
AB  - The hypothesis of the present study is that active immunization of cows against
      inhibin would neutralize endogenous inhibin, increase circulating levels of
      follicle stimulating hormone, and subsequently affect follicular dynamics and the
      ovulation rate during the estrous cycle. Thirteen cows were immunized against
      inhibin alpha-subunit and, 6 cows were immunized with a placebo. Both groups were
      given 4 booster immunizations 7, 14, 21, and 34 weeks after the primary
      injection. Ovaries were examined daily after the 2nd, 3rd, and 4th booster
      immunizations by transrectal ultrasonography for 25 days. After the 4th booster
      immunization, blood samples were collected daily for one complete estrous cycle
      to measure FSH and LH. The results showed that the immunized cows generated
      antibodies against inhibin, and that they had higher FSH levels compared with the
      controls. The number of follicular waves during the estrous cycle was higher in
      the immunized cows (3 or 4 waves) than in the controls (2 or 3 waves). Moreover,
      the immunized cows had a greater number of follicles during the estrous cycle
      compared with the control cows. The maximum number of follicles was 14.8 +/- 1.7
      vs 5.4 +/- 0.2 in inhibin-immunized and control cows, respectively, during the
      first follicular wave and 13.9 +/- 1.9 vs 5.6 +/- 0.7, respectively, during the
      ovulatory wave. Multiple ovulations were increased in the immunized cows.
      However, the ovulation rate varied greatly in the immunized animals. In
      conclusion, immunization against inhibin increased FSH secretions during the
      estrous cycle in the cows. Moreover, the immunized cows had a greater number of
      follicular waves during the estrous cycle and a greater number of follicles, and
      this could be used as a potential source of oocytes for use in IVF/embryo
      transfer programs.

PMID- 16293941
TI  - Body temperature and circulating progesterone levels before and after parturition
      in killer whales (Orcinus orca).
AB  - Killer whales were used to evaluate peripartum changes and interactions between
      body temperature and circulating progesterone concentration. Daily body
      temperature was measured between 0800 h and 0830 h before activity. Body
      temperature clearly increased during the first phase of pregnancy, and this was
      followed by a gradual decline until full term. The initial increase was
      paralleled by circulating levels of progesterone. A decrease in body temperature
      was first detected on day 5 (p < 0.01) before parturition, and body temperature
      decreased significantly every 2 days until delivery. Five days before delivery,
      body temperature was 0.3 C lower than the mean value during the pregnancy period,
      and the decrease was more marked on day 1 before delivery (0.8 C). Serum
      progesterone levels during pregnancy showed a general pattern of initial rapid
      elevation (increasing phase), followed by a gradual decline (decreasing phase)
      throughout the remainder of pregnancy. However, statistically significant
      correlations between body temperature and progesterone pattern were only found
      only during the increasing phase. These results suggest that monitoring body
      temperature variation can be considered valuable for predicting impending
      parturition in killer whales.

PMID- 16293942
TI  - Relations between plasma IGF-I concentrations during treatment with CIDR-based or
      Ovsynch protocol for timed AI and conception in early postpartum Japanese black
      beef cows.
AB  - We examined the relations between plasma insulin-like growth factor (IGF) -I
      concentrations during treatment with CIDR-based or Ovsynch protocol for timed AI
      and conception and plasma steroid concentrations in early postpartum Japanese
      Black beef cows. Cows in the control group (Ovsynch; n = 21) underwent Ovsynch
      protocol (GnRH analogue on Day 0, PGF(2alpha) analogue on Day 7, and GnRH
      analogue on Day 9), with AI on Day 10, approximately 20 h after the second GnRH
      treatment. Cows in the Ovsynch+CIDR group (n = 22) received Ovsynch protocol plus
      a CIDR for 7 days (starting on Day 0). Cows in the further treatment group
      (EB+CIDR+GnRH; n = 22) received 2 mg of estradiol benzoate (EB) on Day 0 in lieu
      of the first GnRH treatment, followed by the same treatment as in the
      Ovsynch+CIDR protocol. Plasma IGF-I concentrations were determined on Days -7, 0,
      7, 9 and 17. Conception rates were improved in the CIDR-combined groups (both
      CIDR-treated groups were combined) relative to Ovsynch group (P < 0.05) for cows
      with low IGF-I concentrations (<1,000 ng/ml) on Days -7, 0, and 7, but improved
      conception rate produced by the CIDR-based protocols did not occur in cows with a
      high IGF-I concentration (> or =1,000 ng/ml). Plasma estradiol-17beta
      concentrations increased from Day 0 to 7 (P < 0.05) and were unchanged from Day 7
      to 9 in the Ovsynch group with low IGF-I concentrations on Day 0, while they were
      unchanged from Day 0 to 7 and increased from Day 7 to 9 (P < 0.05) in the Ovsynch
      group with high IGF-I concentrations on Day 0 and in the CIDR-combined group.
      Plasma progesterone concentrations in the Ovsynch group with low IGF-I
      concentrations on Day 0 were higher on Day 14 than in the Ovsynch group with high
      IGF-I concentrations on Day 0 and in the CIDR-combined group (P < 0.05). In
      conclusion, CIDR-based protocols may improve conception relative to Ovsynch in
      early postpartum beef cows with lower plasma IGF-I concentrations at the start of
      the protocols. This improvement is probably due to prevention of premature
      increases of estradiol-17beta and progesterone concentrations, which occurred in
      cows with low IGF-I concentrations treated with Ovsynch, by the CIDR treatment.

PMID- 16293943
TI  - Effect of group culture and embryo-culture conditioned medium on development of
      bovine embryos.
AB  - We investigated the effect of group culture on bovine embryo development, and
      also investigated the effect of embryo-culture conditioned medium on
      developmental competence of individually cultured bovine embryos. Slaughterhouse
      derived bovine oocytes were matured and fertilized in vitro. The presumptive
      zygotes were cultured individually or cultured in groups of 2 to 5 embryos with a
      constant culture density (5 mul/embryo). After 7 days of culture, the rates of
      embryos developed to the blastocyst stage were significantly higher (P < 0.05) in
      group cultures of more than 3 embryos/drop than for embryo culture of 1 or 2
      embryos/drop. These results suggest a beneficial effect of group culture may be
      exerted by possible growth promoting factors secreted by embryos. In the next
      experiment, we investigated the effect of timing of fresh medium replacement on
      the development of embryos cultured in groups. The blastocyst formation rate was
      lower when culture medium was replaced freshly on days 2-4 after fertilization
      than on days 5-6. The blastocyst formation rates of single-cultured embryos were
      significantly (p < 0.05) increased by the addition of conditioned medium derived
      from multiple-embryo culture. These results indicate that group culture promotes
      embryo development and that embryo culture-derived conditioned medium is
      effective for supporting development of single cultured embryos.

PMID- 16293945
TI  - Effect of the dominant follicle aspiration before or after luteinizing hormone
      surge on the corpus luteum formation in the cow.
AB  - Luteinizing hormone (LH) surge and follicle rupture act as trigger to start
      corpus luteum (CL) formation. Thus, we aimed to investigate whether a dominant
      follicle that has not been exposed to an LH surge can become a functional CL. For
      this purpose, follicular fluid from the dominant follicles (DF) of cows was
      aspirated before or after a GnRH-induced LH surge, and subsequent CL formation
      was observed. Holstein cows were divided into four groups as follows: Luteal
      phase, a DF was aspirated 7 days after GnRH injection; Pre-LH surge, a DF was
      aspirated 42 h after PGF(2alpha) injection during the mid luteal phase; Post-LH
      surge, a DF was aspirated 24 h after GnRH injection following PGF(2alpha); and
      Intact follicle, ovulation was induced by GnRH injection after PGF(2alpha).
      Observation of morphological changes in the aspirated follicle using color
      Doppler ultrasonography and blood sampling was performed on Days 0, 3, 6, and 9
      (Day 0 = follicle aspiration). CL formation following DF aspiration was observed
      only in the Post-LH surge group. In both the Luteal phase and Pre-LH surge
      groups, however, none of the cows showed local blood flow at the aspirated site
      or CL formation. Luteal blood flow area, CL volume, and plasma progesterone
      concentration in the Post-LH surge group were no different from those in the
      Intact follicle group. The present results clearly demonstrate that rather than
      follicle rupture, it is the LH surge that is essential for CL formation in cows.

PMID- 16293944
TI  - Design of hammerhead ribozymes that cleave murine Sry mRNA in vitro and in vivo.
AB  - As the first step in investigating the possiblity of applying ribozyme technology
      to artificial control of the sex ratios at birth in farm animals, where the
      demand for females exceeds that for males, we designed a hammerhead ribozyme
      (HHRz) and 2 tRNA(val)-hammerhead ribozyme complexes (tRNARz3 and tRNARz4), and
      examined their effects upon murine Sry mRNA in vitro and in cells. We
      demonstrated that HHRz and tRNARz3 could effectively cleave the target Sry mRNA
      in vitro. For the purpose of experiments in vivo, HHRz was cloned into the highly
      efficient pUC-CAGGS mammalian expression vector (pCAG/HHRz), and the tRNA
      ribozyme complexes were cloned into the pol III promoter-driven pPUR-KE vector
      (pPUR/tRNARz3 and pPUR/tRNARz4); the ribozyme vectors were co-transfected with
      the target vector (pCAG/Sry). A suppressive action (up to approx. 60%) was
      confirmed for pCAG/HHRz and pPUR/tRNARz3 upon the transiently expressed
      exogenously introduced Sry in M15 cultured cells.

PMID- 16293946
TI  - Postnatal developmental changes in immunohistochemical localization of alpha
      smooth muscle actin (SMA) and vimentin in bovine testes.
AB  - The present study demonstrates the postnatal developmental changes in
      immunohistochemical localization of alpha-smooth muscle actin (SMA) and vimentin
      in the bovine testis. In the peritubular myoid cells of seminiferous tubules and
      the sub-epithelial and stromal cells of straight tubules and the rete testis,
      alpha-SMA starts appearing at around 4 months of age. Peritubular alpha-SMA
      attains the continuous mature pattern at around 5 months of age whereas sub
      epithelial and stromal alpha-SMA increases with advancing age. Vimentin is
      localized in the perinuclear zone of Sertoli cells, peritubular and vascular wall
      cells, a few interstitial cells, and in the basal part of the epithelia of
      straight and rete tubules. Developmental changes are only evident in the Sertoli
      cell vimentin, which is basal and weak at birth and increases moderately until 4
      months of age. From around 5 to 8 months of age when the Sertoli cells are under
      morphological transformation, vimentin intensity is considerably increased and
      the characteristic vimentin extensions connect the Sertoli nuclei to the basal
      membrane. These extensions get shorter at around 9 month of age as the Sertoli
      nuclei are positioned basally. The mature Sertoli cell perinuclear vimentin is
      strong and stable without infranuclear extension. In conclusion, the age of
      appearance of alpha-SMA coincides with the onset of postnatal division of
      spermatogonia, and vimentin may play a key role in stabilizing Sertoli cell
      nuclei during their transformation in bovine.

PMID- 16293947
TI  - Early dural reaction to polylactide in cranial defects in rabbits.
AB  - Restoring the bone integrity to injured calvariae remains a challenge to
      surgeons. In this study, the dural biocompatibility of biodegradable poly-L/DL
      lactide 80/20 and 70/30 defect covers, designed for guided bone regeneration, was
      assessed. In each of the 16 test rabbits, bilateral (8.3 mm) cranial defects were
      created. The different covers were applied to one defect each in every rabbit and
      consisted of three parts: an epicranial cover, a spacer, and a dural cover. All
      defects had closed after 8 weeks due to new bone formation. A few giant cells
      were found at the cover-to-dura interface in equal numbers for both covers. Dural
      bone formation was present in 15 of 16 rabbits and progressed unhindered by the
      defect cover or its early degradation products.

PMID- 16293948
TI  - Expression of p53, EGFR, pRb and bcl-2 proteins in pediatric glioblastoma
      multiforme: a study of 54 patients.
AB  - Pediatric glioblastoma multiforme (GBM) tumors, which have been established as
      'de novo' neoplasms, are known to differ from their adult counterparts in terms
      of biology, genetics and ultimately survival of patients. In order to evaluate
      the utility of markers of tumor biology for refining prognostic assessment, we
      retrospectively analyzed 54 pediatric GBMs (age range 9 months to 15 years)
      occurring at different anatomical sites in the brain, operated at our institute
      between 1995 and 2001. The expression of p53, epidermal growth factor receptor
      (EGFR), bcl-2 and retinoblastoma proteins (pRb) was analyzed by
      immunohistochemistry and the results were compared with the clinical profile, MIB
      1 labeling index (LI) and patient survival. p53 immunoreactivity was noted in
      53.7% of cases, predominantly in thalamic (75%) and cerebral lobar (62.2%),
      followed by brainstem tumors (30%). It was absent in cerebellar tumors. p53
      positive tumors had a higher MIB-1 LI, compared to p53-negative tumors (p=0.003).
      EGFR and bcl-2 overexpression was observed in 25.9% and 33.3% of cases,
      respectively, and loss of pRb expression was evident in only 7.4% of cases,
      indicating that loss of this gene function is not significantly involved in
      pediatric GBMs. p53 and bcl-2 expression were maximally noted in patients with
      poorer outcome. Our results indicate that p53 expression status is noted in a
      significant number of pediatric supratentorial neoplasms. p53 with bcl-2
      overexpression is more often associated with ominous prognosis. Further molecular
      characterization would provide newer insights into the biology of these neoplasms
      and form a basis for future therapeutic decision making.

PMID- 16293949
TI  - Shunt revisions in children--can they be avoided? Experiences from a population
      based study.
AB  - BACKGROUND: Shunt failure is by far the most frequent problem in children with
      shunts, and most of them will experience this condition at some point in their
      lives. In order to identify causes of shunt failure, and to compare multi
      component and one-piece shunt systems, we analyzed retrospectively all pediatric
      shunt procedures in our Department during an 11-year period. The study does not
      deal with shunt infections. METHODS: We reviewed the records of all pediatric
      shunting procedures between January 1986 and December 1996. RESULTS: The study
      included 161 children operated for hydrocephalus with a total of 431 procedures.
      The procedures included 124 (29%) primary insertions, 10 (2%) reinsertions and
      297 (69%) revisions; 206 (69%) of the revisions were due to shunt failures, of
      which 74 (36%) were caused by the failure of the surgical technique (misplaced
      ventricular catheters, disconnected shunts, or misplaced peritoneal catheters).
      CONCLUSIONS: Improvement of the surgical technique may reduce the incidence of
      shunt failures and revisions. The results obtained in a small department like
      ours do not seem to differ substantially from those obtained in more specialized
      departments with a larger patient group. Practical measures that may reduce the
      risk of shunt failures are suggested.

PMID- 16293950
TI  - The retrograde ventriculo-sinus shunt (El Shafei RVS shunt). Rationale,
      evolution, surgical technique and long-term results.
AB  - Since 1990, 110 retrograde ventriculo-sinus (RVS) shunts were implanted; 98
      patients (89.1%) benefited - 1 of them (0.9%) after shunt revision. The
      manifestations of high intra cranial pressure (ICP) disappeared, there were no
      problems related to improper cerebrospinal fluid (CSF) drainage, and the
      transcranial Doppler (TCD) resistive index (RI) measurements decreased to within
      normal ranges. Radiologically, the ventriculomegaly showed no regression in
      patients with open craniums and variable degrees of mild regression in patients
      with rigid craniums. Complications that needed shunt removal or revision occurred
      in 13 patients (11.8%); 1 patient (0.9%) died before shunt revision; they were
      all due to technical errors committed during the stages of evolution of the
      surgical technique for shunt implantation. The follow-up ranged between 4 months
      and 11 years (mean 3.42 years). CONCLUSION: the RVS shunt is a simple, minimally
      invasive, physiological procedure for treatment of hydrocephalus and is suitable
      for all ages.

PMID- 16293952
TI  - Primary endovascular therapy with clot retrieval and balloon angioplasty for
      acute basilar artery occlusion.
AB  - This case report demonstrates that mechanical clot disruption and retrieval may
      be performed safely and successfully in a child with basilar artery (BA)
      thrombosis. A 16-year-old boy presented to our institution with locked-in
      syndrome 20 h after symptom onset. Brain MRI and cerebral angiography findings
      were consistent with BA occlusion. The child underwent endovascular therapy with
      clot retrieval followed by balloon angioplasty achieving immediate recanalization
      and clinical recovery on 3-month follow-up. This case highlights the use of
      primary neurointerventional devices in children with BA occlusion presenting
      beyond the conventional therapeutic window for other interventions.

PMID- 16293951
TI  - Acute basilar artery dissection treated by emergency stenting in a 13-year-old
      boy.
AB  - We report a 13-year-old boy who presented with acute basilar artery occlusion due
      to traumatic arterial dissection. Because a grave prognosis was expected if left
      untreated, and the chance of neurological recovery was believed to be unlikely
      but not zero, given that emergency stenting for the dissection was performed
      within 6 h of ictus. Recanalization of the basilar artery with stent placement
      did not change the poor prognosis in this patient because there was extension of
      dissection into the posterior cerebral arteries.

PMID- 16293953
TI  - Three unusual arteriovenous fistulas presenting in young children successfully
      treated with transarterial endovascular embolization.
AB  - Endovascular approaches can be utilized to manage arteriovenous fistulas (AVFs)
      either as a stand alone therapy or in conjunction with surgical excision. The
      goal of treatment is to completely obliterate the AVF. These vascular
      malformations are rare in childhood and pose a treatment challenge. We describe 3
      children who were diagnosed with vascular malformations on magnetic resonance
      imaging and were subsequently found to have unusual AVFs on angiography. These
      single-feeder fistulas were successfully occluded with transarterial embolization
      using platinum coils.

PMID- 16293954
TI  - Paraparesis secondary to expansion of cervical syrinx: an unusual presentation of
      ventriculo-peritoneal shunt malfunction.

PMID- 16293955
TI  - Complete intraventricular unisystem ventriculoperitoneal shunt migration.

PMID- 16293956
TI  - Deleterious effects of sleep-disordered breathing on the heart and vascular
      system.
AB  - Obstructive sleep apnea (OSA) is the most common form of sleep-disordered
      breathing, affecting 5-15% of the population. It is characterized by intermittent
      episodes of partial or complete obstruction of the upper airway during sleep that
      disrupts normal ventilation and sleep architecture, and is typically associated
      with excessive daytime sleepiness, snoring, and witnessed apneas. Patients with
      obstructive sleep apnea present risk to the general public safety by causing 8
      fold increase in vehicle accidents, and they may themselves also suffer from the
      physiologic consequences of OSA; these include hypertension, coronary artery
      disease, stroke, congestive heart failure, pulmonary hypertension, and cardiac
      arrhythmias. Of these possible cardiovascular consequences, the association
      between OSA and hypertension has been found to be the most convincing. Although
      the exact mechanism has not been understood, there is some evidence that OSA is
      associated with frequent apneas causing mechanical effects on intrathoracic
      pressure, cardiac function, and intermittent hypoxemia, which may in turn cause
      endothelial dysfunction and increase in sympathetic drive. Therapy with
      continuous positive airway pressure has been demonstrated to improve
      cardiopulmonary hemodynamics in patients with OSA and may reverse the endothelial
      cell dysfunction. Despite the availability of diagnostic measures and effective
      treatment, many patients with sleep-disordered breathing remain undiagnosed.
      Therefore, OSA continues to be a significant health risk both for affected
      individuals and for the general public. Awareness and timely initiation of an
      effective treatment may prevent potential deleterious cardiovascular effects of
      OSA.

PMID- 16293957
TI  - Successful treatment of sarcoidosis-associated pulmonary hypertension with
      bosentan.
AB  - Sarcoidosis is a systemic granulomatous disease of unknown etiology, in which the
      lungs and intrathoracic lymph nodes are predominant sites of involvement.
      Pulmonary hypertension is a known complication of sarcoidosis. Treatment of
      sarcoidosis-associated pulmonary hypertension has traditionally focused on the
      initiation of systemic corticosteroids, but has had inconsistent results. We
      present a patient with sarcoidosis-associated pulmonary hypertension who achieved
      substantial clinical improvement with the dual endothelin receptor antagonist
      bosentan.

PMID- 16293958
TI  - Efficacy of nebulized flunisolide combined with salbutamol and ipratropium
      bromide in stable patients with moderate-to-severe chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: The efficacy of nebulized corticosteroids in the prevention of
      exacerbation of chronic obstructive pulmonary disease (COPD) has been poorly
      studied. OBJECTIVE: To evaluate the efficacy and tolerability of nebulized
      flunisolide (1 mg) + salbutamol/ipratropium bromide (1,875/375 microg) b.i.d. in
      comparison with placebo + salbutamol/ipratropium bromide. METHODS: This was a
      randomized, parallel-group, double-blind study on 114 patients with COPD of
      moderate-to-severe degree. The main outcome was the frequency of severe
      exacerbations over a 6-month period. Before and after treatment, respiratory
      symptoms, forced expiratory volume in 1 s (FEV(1)), shuttle walking test distance
      and St. George's Respiratory Questionnaire scores were evaluated. RESULTS: The
      total number of exacerbations was slightly lower in the flunisolide group
      compared to the placebo group (19 vs. 34, p = 0.054); the number of patients
      experiencing at least one exacerbation during the study was also decreased (16
      vs. 26, p = 0.059). In particular, type 3 Anthonisens's exacerbations were
      significantly reduced by flunisolide (p = 0.044). In the placebo group, scores
      were higher than in the flunisolide group but nonsignificant for dyspnea, cough,
      sputum amount and purulence. FEV(1) was significantly increased compared to
      baseline in both groups, and the area under the FEV(1)-time curve during the 6
      month period was significantly greater in the flunisolide group (5.2 +/- 10.6 vs.
      2.1 +/- 5.0, flunisolide vs. placebo, respectively; p = 0.047). For shuttle
      walking test distance and scores of the St. George's Respiratory Questionnaire,
      no significant difference between the baseline evaluation and the end of the
      study was observed in both groups. CONCLUSIONS: Nebulized flunisolide is a good
      alternative to other inhaled corticosteroids when added to nebulized
      salbutamol/ipratropium bromide in the long-term treatment of moderate-to-severe
      COPD patients.

PMID- 16293959
TI  - Asthma control following initial inhaled corticosteroid monotherapy in mild to
      moderate asthma: a 4- to 8-week observational study.
AB  - BACKGROUND: There is an increasing trend for the use of combination therapy of
      inhaled corticosteroids (ICS) and long-acting beta(2)-agonists as initial
      treatment for asthma. OBJECTIVE: To assess the efficacy of initial monotherapy
      with ICS for achieving asthma control in steroid-naive mild to moderate
      asthmatics. METHOD: During an observational survey, steroid-naive patients
      received ICS in a dosage of 400-2,000 mug/day. After 4-8 weeks' treatment,
      achievement of asthma control, defined according to the Global Initiative for
      Asthma (GINA) guidelines, was assessed and the Asthma Control Questionnaire (ACQ)
      was completed. RESULTS: Among 537 selected patients, 21 were excluded because of
      severe asthma and 96 because of inadequate ICS daily dosage. Four hundred and
      twenty patients were analyzed, 396 (94%) of whom completed the survey. Mean ICS
      dosage, in equivalent beclomethasone, was 479 +/- 62 mug/day for mild asthma
      (group A) and 1,115 +/- 306 mug/day for moderate asthma (group B). Asthma control
      was achieved for 71 and 65% of the patients, mean ACQ score improved from 1.1 +/-
      0.6 to 0.5 +/- 0.5 (p < 0.001) and from 2.0 +/- 0.8 to 0.8 +/- 0.7 (p < 0,001),
      and FEV(1) (% predicted) improved from 93 +/- 9 to 96 +/- 13 (p < 0.05) and from
      85 +/- 15 to 91 +/- 15 (p < 0.001) for groups A and B, respectively. CONCLUSION:
      Asthma control can be achieved by ICS monotherapy for two thirds of steroid-naive
      patients with mild to moderate asthma. For these patients, we suggest that ICS
      alone could be started as initial therapy and that additional therapy should be
      considered after 4-8 weeks for patients who do not achieve control.

PMID- 16293960
TI  - Music during bronchoscopic examination: the physiological effects. A randomized
      trial.
AB  - BACKGROUND: Patients scheduled for bronchoscopic procedures are often anxious and
      frightened. Reduction in the state of anxiety during an invasive procedure may
      prevent some possible complications. Music has been proposed as a safe
      nonpharmacological antianxiety intervention. OBJECTIVE: We followed up
      physiological indicators of anxiety (blood pressure, heart rate) during
      bronchoscopic examination to determine the effect of music on the level of
      anxiety. METHODS: Two hundred adult patients were included in the study. Blood
      pressure, heart rate, procedures performed during bronchoscopy and duration of
      examination were monitored. Patients' overall feelings during the procedure were
      rated from 0 (without unpleasant feelings) to 10 (unbearable). All patients used
      the Visual Analogue Scale (VAS). RESULTS: Two hundred adult patients referred for
      bronchoscopy were included in the study: 93 patients received music during the
      procedure and 107 served as control. There were no significant differences
      between the two groups in terms of age, sex, indications for bronchoscopy,
      procedures performed during bronchoscopy, duration of the examination and
      patients' subjective perception of the procedure. The mean hart rate, systolic
      and diastolic blood pressures were significantly lower in the music group
      compared to the control group. CONCLUSIONS: Our findings suggest that the
      application of music reduces anxiety during bronchoscopic examination as
      physiological indicators of anxiety, the mean heart rate, systolic and diastolic
      blood pressures, were significantly lower in the music group.

PMID- 16293961
TI  - Cardiac troponin I in asphyxiated neonates.
AB  - BACKGROUND: Cardiac troponins T (cTnT) and I (cTnI) are well-established markers
      in detecting myocardial ischemic damage in adults. Perinatal asphyxia is
      associated with cardiac dysfunction. OBJECTIVES: To evaluate serum concentrations
      of cTnI in asphyxiated neonates and to investigate whether cTnI is correlated
      with the traditional markers of asphyxia. METHODS: Blood samples were collected
      from 13 asphyxiated neonates (umbilical artery pH<7.18 and either a 1-min Apgar
      score<4 or a 5-min Apgar score<7) and 39 controls. Data on gestation, birth
      weight, sex, Apgar scores, mode of delivery, umbilical pH, creatinine, serum
      activity of aspartate and alanine aminotransferase, and QTc interval were
      investigated. RESULTS: Median (range) cTnI concentrations were significantly
      higher in asphyxiated neonates with respect to healthy infants: 0.36 microg/l
      (0.05-11) versus 0.04 microg/l (0.04-0.06); p<0.01. In asphyxiated babies, no
      statistically significant correlations were found between concentrations of cTnI
      and the other markers of asphyxia. CONCLUSIONS: In asphyxiated neonates, cTnI
      concentrations are higher with respect to healthy infants, suggesting the
      presence of myocardial damage in this group of high-risk patients. cTnI does not
      correlate with the traditional markers of asphyxia.

PMID- 16293962
TI  - Effects of oral administration of insulin-like growth factor-I on circulating
      concentration of insulin-like growth factor-I and growth of internal organs in
      weanling mice.
AB  - Insulin-like growth factor (IGF)-I is a polypeptide that mediates the growth
      promoting action of growth hormone in postnatal animals. The present study was
      conducted to examine whether orally administered IGF-I would be absorbed into the
      general circulation and also whether ingested IGF-I would enhance the growth of
      whole body as well as internal organs, and tissues in 3-week-old ICR-strain
      female weanling mice. In experiment (Exp) 1, a total of 70 mice received IGF-I
      orally at 1 microg.g-1 in 0.2-ml PBS or the vehicle alone. Concentrations of IGF
      I and glucose in heart blood were measured after killing 5 animals in each group
      every fourth hour during a 24-hour period. In Exp 2, a total of 40 mice received
      oral IGF-I administration at 1 microg.g-1 or vehicle every third day beginning
      from day 0 for a 13-day period. Half the animals were killed at day 7 and the
      other half at day 13. Weights of whole body and organs/tissues (small intestine,
      liver, thigh muscle, and brain) were measured every day and at slaughter,
      respectively. In Exp 1, following the oral IGF-I administration, serum IGF-I
      concentration increased at hour 4 (p<0.01) and returned to the hour 0 level by
      hour 8, whereas glucose concentration was lowest at hour 4 and returned to the
      hour 0 level by hour 16. In the PBS-fed group, neither IGF-I nor glucose
      concentration changed during the 24-hour period. In Exp 2, weight of small
      intestine increased (p<0.05) in response to the oral IGF-I, whereas weights of
      liver and thigh muscle of the IGF-I-fed group were greater (p<0.01) and tended to
      be greater (p=0.06), respectively, than those of the PBS-fed only at day 13.
      However, brain weight and serum concentrations of IGF-I and IGF-II were not
      affected by oral IGF-I administration. Results suggest that although orally
      administered IGF-I mainly acts at the intestine, a portion of ingested IGF-I is
      absorbed into the general circulation to enhance the growth of selective
      organs/tissues in weanling mice.

PMID- 16293963
TI  - Spontaneous contraction of pseudoglandular-stage human airspaces is associated
      with the presence of smooth muscle-alpha-actin and smooth muscle-specific myosin
      heavy chain in recently differentiated fetal human airway smooth muscle.
AB  - BACKGROUND: Recent investigations demonstrating that pseudoglandular-stage
      airspaces contract spontaneously suggest that the production of contractile
      proteins by airway wall smooth muscle (ASM) is an important factor in the
      functional and structural differentiation of ASM. AIMS: Ouraim was to determine
      if smooth muscle (SM)-myosin heavy chain (MHC) myofilaments, the 'motor'
      underlying SM contraction, and SM-alpha-actin myofilaments were distributed
      simultaneously in pseudoglandular-stage human lungs and to further define the
      nature of fetal airway contractions. METHODS: Immunohistochemically stained
      sections of fetal lung (14 fetuses, 10.1-17 weeks gestation) were analysed by
      computer-assisted morphometry to determine airspace dimensions and detect SM-MHC-
      and SM-alpha-actin-ASM. Lung tissue from the same fetuses was also placed in
      explant culture to observe airway contractions using videomicroscopy. We found
      that the smallest airspaces were just as likely to be invested by a layer of SM
      MHC-positive ASM as by a layer of SM-alpha-actin-positive ASM. In addition,
      larger airways or airways from more mature fetal lungs were more likely to be
      invested by either SM-MHC- or SM-alpha-actin-positive ASM. Spontaneous airspace
      contractions were peristalsis-like and variable in amplitude. The time interval
      between contractions was temperature dependent (mean+/-SEM, 44+/-7.5 s at 37
      degrees C), shortened by carbachol and increased by nitric oxide (NO)-donating
      drugs. CONCLUSIONS: These observations suggest that ASM differentiation is
      characterised by the simultaneous production of SM-alpha-actin and SM-MHC
      myofilaments and that the presence of these proteins is likely to be responsible
      for cholinergic- and NO-sensitive spontaneous contractions of fetal human
      airspaces.

PMID- 16293964
TI  - Pseudocyst treatment in chronic pancreatitis--surgical treatment of the
      underlying disease increases the long-term success.
AB  - BACKGROUND: For reasons of persisting controversies concerning indications for
      surgery, we evaluated chronic pancreatitis patients following pancreatic head
      resection or drainage procedure for pseudocysts located in the pancreatic head.
      MATERIAL AND METHODS: 206 patients (166 male, 40 female) with chronic
      pancreatitis and pseudocysts in the pancreatic head were operated between April
      1982 and July 2001. 169 patients (82%) were treated with the duodenum-preserving
      pancreatic head resection, a pseudocyst-jejunostomy was performed in 37 patients
      (18%). RESULTS: The hospital mortality was 0.4%. The late mortality was 19% in a
      median follow-up of 7.3 years. The rate of patients with complete relief of pain
      was significantly higher after resection compared to drainage procedure in the
      long-term follow-up (94 vs. 75%; p = 0.003). With regard to recurrence of
      pseudocysts, patients had an elevated rate of reoperations following drainage
      procedure (13 vs. 1%; p = 0.008). The endocrine function was significantly better
      preserved in patients of the drainage group compared to the resection group (no
      diabetes 67 vs. 35%, p < 0.01). CONCLUSION: The resection has, compared to
      drainage procedures alone, the advantage of low recurrence rate of pseudocysts
      and a high rate of pain-free patients in the long-term follow-up. However, the
      risk of diabetes is increased in the resection group.

PMID- 16293965
TI  - Nutritional support and oral intake after gastric resection in five northern
      European countries.
AB  - BACKGROUND: A comprehensive evidence base for perioperative care in upper
      gastrointestinal (GI) surgery is lacking. Little is known about the routines
      currently practiced in the absence of such evidence. We describe postoperative
      practice after gastric resections in five northern European countries. METHOD AND
      SETTING: Questionnaire survey in all major digestive surgical centres in
      Scotland, the Netherlands, Denmark, Sweden and Norway. RESULTS: 76% of all
      centres (n = 200/263) responded. Routines varied extensively both nationally and
      between countries. No uniformity was traced although a conservative trend was
      noticeable in the use of nasogastric decompression tubes and 'nil-by-mouth'
      regimens. Nutritional support during the first 5 days is generally offered in
      Denmark, but not in Scotland. Drinking at will is generally allowed in Denmark
      and Norway by the first postoperative day. Eating at will is uniformly
      restricted. CONCLUSION: The paucity of evidence is reflected by the marked
      heterogeneity in practice. Large groups of patients may be treated suboptimally.
      Best perioperative care for these patients must be defined and documented.
      Especially, the role of early oral intake at will in upper GI surgery needs to be
      clarified by sufficiently powered trials.

PMID- 16293967
TI  - Mutational analysis of amino acid positions crucial for IgE-binding epitopes of
      the major apple (Malus domestica) allergen, Mal d 1.
AB  - BACKGROUND: Individual amino acid residues of the major birch pollen allergen,
      Bet v 1, have been identified to be crucial for IgE recognition. The objective of
      the present study was to evaluate whether this concept was applicable for the Bet
      v 1-homologous apple allergen, Mal d 1. METHODS: A Mal d 1 five-point mutant was
      produced by PCR techniques, cloned into pMW 172 and expressed in Escherichia coli
      BL21(DE3) cells. To evaluate the allergenic properties of the engineered protein
      compared to Mal d 1 wild-type IgE immunoblotting, ELISA, peripheral blood
      monocytes proliferation assays, and skin prick tests were performed. RESULTS: The
      Mal d 1 mutant showed reduced capacity to bind specific IgE as compared to wild
      ype Mal d 1 in in vitro assays in the majority of the sera tested. In ELISA, 10
      out of 14 serum samples displayed an 88-30% decrease in IgE binding to Mal d 1
      mutant compared to wild-type Mal d 1. Skin prick tests in apple-allergic patients
      (n = 2) confirmed the markedly decreased ability of the Mal d 1 mutant to induce
      allergic reactions in vivo. However, the relevant T cell epitopes were present in
      the mutated molecule according to peripheral blood mononuclear cell proliferation
      assays. CONCLUSIONS: Our findings suggest that it is possible to modulate the IgE
      binding properties of allergens by single amino acid substitutions at crucial
      positions which might be useful for future immunotherapy of birch-pollen
      associated food allergies which are not ameliorated by birch pollen
      immunotherapy.

PMID- 16293966
TI  - Influence of surgical resection and post-operative complications on survival
      following adjuvant treatment for pancreatic cancer in the ESPAC-1 randomized
      controlled trial.
AB  - BACKGROUND/AIMS: The influence of type of surgery and occurrence of post
      operative complications on survival following adjuvant therapy for pancreatic
      cancer are uncertain. METHODS: Cox proportional hazard modelling was used to
      investigate the influence of type of surgery and the presence of complications on
      survival in conjunction with clinico-pathological variables in the 550 patients
      of the ESPAC-1 adjuvant randomized controlled trial. RESULTS: Standard Kausch
      Whipple (KW) was performed in 282 (54%) patients, 186 (35%) had a pylorus
      preserving (PP) KW, 39 (7%) had a distal pancreatectomy and 21 (4%) had a total
      pancreatectomy. Post-operative complications were reported in 140 (27%) patients.
      PP-KW patients survived longer with a median (95% CI) survival of 19.9 (17.3,
      23.1) months compared to 14.8 (13.0, 16.7) for KW patients (chi(2)(LR) = 15.1, p
      < 0.001). KW patients were more likely however to have R1 margins (67 (24%) vs.
      29 (16%), chi(2) = 4.59, p = 0.032), poorly differentiated tumours (70 (26%) vs.
      19 (10%), chi(2) = 18.65, p < 0.001) and positive lymph nodes (165 (60%) vs. 81
      (44%), chi(2) = 11.32, p < 0.001). Post-operative complications did not
      significantly affect survival. Independent prognostic factors were tumour grade,
      nodal status and tumour size but not type of surgery or post-operative
      complications. There was a survival benefit for chemotherapy irrespective of the
      type of surgery or post-operative complications. CONCLUSIONS: The KW and PP-KW
      procedures did not significantly influence the hazard of death in the presence of
      tumour staging, demonstrating that ESPAC-1 surgeons showed good judgement in
      their choice of operation. Post-operative complications did not adversely affect
      the survival benefit from adjuvant chemotherapy.

PMID- 16293968
TI  - Orchidectomy modulates alpha2-adrenoceptor reactivity in rat mesenteric artery
      through increased thromboxane A2 formation.
AB  - The present study evaluates the effect of endogenous male sex hormones on the
      reactivity to alpha2-adrenoceptor activation, and to analyze the role of the
      endothelium in this response in intact and endothelially denuded superior
      mesenteric arteries from control and orchidectomized male Sprague-Dawley rats.
      The concentration-dependent constriction induced by clonidine was analyzed in the
      absence and presence of the nitric oxide synthase (NOS) inhibitor, Nomega-nitro-L
      arginine (L-NAME), cyclooxygenase (COX-1 and COX-2) inhibitors, indomethacin, the
      specific COX-2 inhibitor NS-398, the thromboxane-prostanoid receptor antagonist
      SQ29,548 and the thromboxane A2 (TXA2) synthase inhibitor, furegrelate.
      Endothelial NOS (eNOS), COX-2 and TXA2 synthase protein expression was studied by
      Western blot analysis. In addition, the basal and clonidine-stimulated production
      of TXB2, the stable TXA2 metabolite, was also measured. In intact vessels from
      control male rats, the concentration-dependent constriction induced by clonidine
      was increased by both L-NAME or endothelial removal, unaltered by indomethacin
      and decreased by NS-398; in denuded vessels, the clonidine response was decreased
      by NS-398 and unaltered by L-NAME, indomethacin, SQ29,548 or furegrelate. In
      intact vessels from orchidectomized rats, the constriction induced by clonidine
      was increased by L-NAME but practically abolished by indomethacin or NS-398; in
      endothelially denuded segments the clonidine response was unaltered by L-NAME,
      but was decreased by indomethacin, NS-398, SQ29,548 or furegrelate. Orchidectomy
      failed to modify eNOS,COX-2 and TXA2 synthase expression, and increased basal and
      clonidine-stimulated TXB2 release. These results show that TXA2 produced in
      smooth muscle cells is increased in mesenteric arteries from orchidectomized rats
      compared to their controls, and that this prostanoid is functionally involved in
      the vasoconstrictor response to clonidine only in arteries from the
      orchidectomized rats.

PMID- 16293969
TI  - Evaluation of enzymes involved in proteoglycan degradation in the wall of
      abdominal aortic aneurysms.
AB  - The abdominal aortic aneurysm (AAA) wall represents an extreme example of
      arterial remodeling with disturbed elastin, collagen and proteoglycan metabolism.
      The aim of this study was to evaluate enzymes involved in the degradation of
      glycosaminoglycan chains and core proteins of proteoglycans in the AAA wall. The
      study material consisted of wall samples from 10 AAA. Fragments of 5 normal
      abdominal aortas from organ donors were used as a control. The activity of
      endoglycosidases, exoglycosidases and sulfatases was measured using colorimetric
      methods. To assess matrix metalloproteinases (MMPs), Western blot and zymography
      were performed. The activity of endoglycosidase degrading chondroitin-4-sulfate
      was lower in the AAA wall. Endoglycosidase degrading heparan sulfate and dermatan
      sulfate, arylosulfatase B, as well as all the exoglycosidases assessed
      demonstrated higher activities in the AAA wall. Furthermore, increased expression
      of MMP1, MMP2 and MMP9 was also shown in the AAA wall. Zymography revealed
      decreased activity of pro-MMP2 and presence of pro-MMP9 in the AAA wall compared
      to the wall of normal aorta. Extensive changes in the activity of
      glycosaminoglycan-degrading enzymes and MMPs may influence the organization of
      the extracellular matrix network and lead to previously demonstrated changes in
      the proteoglycan and glycosaminoglycan content in the AAA wall.

PMID- 16293971
TI  - An examination of characteristics of lung and colon cancer patients participating
      in a web-based decision support program. Internet-based decision support
      programs.
AB  - OBJECTIVES: Little is known about the characteristics of cancer patients who
      employ the Internet as a technique to gather information to assist them in their
      management. METHODS: To address this issue, aggregate data from individuals with
      colon (n=7,543), non-small cell lung (n=24,778) and small cell lung (n=13,817)
      cancers who provided personal clinical information through participation in a
      proprietary Web-based decision support program (NexProfiler Treatment Option
      Tools for Cancer; NexCura, Inc., Seattle, Wash., USA) were evaluated for
      potential differences between specific patient subgroups. RESULTS: Examination of
      a number of objective (e.g., prior therapy) and subjective (e.g., overall health,
      activity level) parameters failed to reveal any major differences based on sex,
      geographical location (US vs. non-US) or newly diagnosed versus recurrent disease
      (non-small cell lung cancer patients). Several notable findings included: (1)
      overall >65% of colon cancer patients and >70% of lung cancer patients stated
      that they 'were interested in learning about clinical trials'; (2) 65-70% of
      patients with recurrent non-small cell lung cancer stated that their 'general
      health was good', while >60% noted they had symptoms and >50% declared their
      activity level to be essentially 'normal'; (3) while almost 80% of small cell
      lung cancer patients noted symptoms, >60% stated their activity level was
      'normal'. CONCLUSION: These data suggest that the population of patients who seek
      information from Web-based decision support programs share a number of relevant
      clinical features, yet they appear to represent a unique subset among all
      individuals with malignant disease. It will be important for oncologists to more
      fully understand the objectives of this population in order to assist such
      patients (and their families) in their use of this remarkably powerful, but
      essentially unregulated, technology.

PMID- 16293970
TI  - Gene transfer of vasostatin, a calreticulin fragment, into neuroendocrine tumor
      cells results in enhanced malignant behavior.
AB  - Vasostatin, a fragment of calreticulin, was transfected in the BON cell line to
      evaluate the feasibility of using it for gene therapy in neuroendocrine tumors.
      Vasostatin transfected cells were subcutaneously inoculated in nude mice. Burkitt
      lymphoma cell line, CA46, colorectal adenocarcinoma cell line, SW480, as well as
      endothelial cells PAE and SVEC4 were used for evaluating the function of
      vasostatin. The results demonstrated that vasostatin transfer caused enhanced
      malignant behavior of neuroendocrine tumor cell line, BON. Cell adhesion,
      spreading and cellular invasion were also enhanced in vasostatin-expressing BON
      cells. Tumor suppressor genes including p53, nm23, Rb and vinculin were down
      regulated. Moreover, cell cycle regulatory protein, p27kip1, and cell
      differentiation-related protein kinase, PKR, were also significantly down
      regulated. Furthermore, expression of NKG2D ligands, MICA and MICB, were down
      regulated. Mice implanted with vasostatin-expressing BON cells showed an earlier
      and faster tumor growth compared to wild type. Anti-proliferative effects of
      vasostatin could not be proven in other cells except in PAE. These results
      indicated that vasostatin does probably not have a tumor growth inhibitory effect
      by itself, but rather modulates processes which are necessary for tumor growth.
      Therefore, one should be very careful when using vasostatin as an anti-tumoral
      agent in clinical trials, at least for neuroendocrine tumors.

PMID- 16293972
TI  - Gastrointestinal stromal tumours: correlation of F-FDG gamma camera-based
      coincidence positron emission tomography with CT for the assessment of treatment
      response--an AGITG study.
AB  - BACKGROUND: Malignant gastrointestinal stromal tumours (GISTs) are a rare subset
      of aggressive mesenchymal tumours specific to the gastrointestinal system. They
      are both locally aggressive and can metastasize. The aim of this analysis was to
      report on our experience of the utility of coincidence positron emission
      tomography (co-PET) based on an 18F-FDG gamma camera in assessing treatment
      response to imatinib using CT as the comparator and the final clinical outcome as
      the end point. METHODS: We compared the results of CT and PET scans as predictors
      of outcome in a consecutive series of patients treated at the Prince of Wales
      hospital. All patients had biopsy-proven malignant GIST and were on treatment
      with the targeted pharmacotherapeutic agent imatinib. The majority of the
      patients were receiving treatment as part of the randomized trial of the European
      Organization for Research and Treatment of Cancer, the Australian
      Gastrointestinal Trials Group and the Italian Sarcoma Group, comparing 400 with
      800 mg (400 mg b.i.d.). The monitoring of tumour response was achieved by serial
      CT measurements according to the RECIST criteria. Concurrent 18F-FDG co-PET
      studies were performed within a mean of 2.8 days from the CT scan and were
      interpreted by a consensus panel of 2 nuclear medicine physicians. RESULTS: A
      total of 18 patients were recruited into the study, with a total of 74 lesions.
      There were 47 liver lesions, 31 of which were identified on the initial 18F-FDG
      co-PET scans (63%). There were 10 primary lesions (4 stomach, 4 duodenal, 2 small
      bowel), 9 of which were demonstrated on initial 18F-FDG co-PET examinations
      (90%). There were 17 extrahepatic metastatic sites, 15 of which were visualized
      on the initial 18F-FDG study (88%). Of the 18 patients, 8 showed concordant
      improvement on both CT and (18)F-FDG co-PET criteria. One patient showed
      concordant worsening and 1 was not FDG avid. Eight patients initially showed
      discordance. 18F-FDG co-PET studies demonstrated changes preceding CT findings in
      all 8 patients with subsequent concordant improvement. CONCLUSION: 18F-FDG co-PET
      is a useful modality to monitor treatment response to imatinib in patients with
      malignant GIST. Although there is a relatively reduced sensitivity when compared
      with CT for the detection of lesions especially in the liver, co-PET changes in
      several instances precede the changes on CT scanning. This modality has the
      potential to influence clinical decision making and should be considered as part
      of the standard care of patients on imatinib.

PMID- 16293973
TI  - Suppressed MKP-1 is an independent predictor of outcome in patients with
      hepatocellular carcinoma.
AB  - OBJECTIVE: An increase in the activity of mitogen-activated protein kinases
      (MAPKs) has been correlated with a more malignant phenotype in several tumor
      models in vivo. This study was designed to clarify the expression of MKP-1 in
      surgically resected hepatocellular carcinoma (HCC). METHODS: We reviewed the
      cases of 77 patients who had undergone initial liver resection for HCC without
      preoperative treatment. Immunohistochemical analysis of MKP-1 was performed on
      paraffin-embedded tissues. The correlation between MKP-1 expression and clinical
      outcome was investigated. RESULTS: Tumor cells were immunohistochemically stained
      for MKP-1 expression, and the same levels as in normal hepatocytes were detected
      in 66 (85%) of 77 HCC patients, being decreased in 11 (15%) HCCs. Decreased MKP-1
      expression significantly correlated with serum alpha-fetoprotein levels and tumor
      size (p<0.05). The disease-free survival rates in MKP-1-negative and -positive
      patients were 0 and 31.0% at 5 years, respectively (p<0.01). The survival rates
      after a surgical resection in MKP-1-negative and -positive patients were 18.2 and
      65.5% at 5 years, respectively (p<0.01). CONCLUSIONS: The MKP-1 expression in HCC
      was an independent prognostic factor for outcome in HCC patients. In the future,
      it will be useful to explore whether the phosphatase expression might account for
      the response to HCC treatments targeting at MAPK activation.

PMID- 16293975
TI  - Microsatellite instability caused by hMLH1 promoter methylation increases with
      tumor progression in right-sided sporadic colorectal cancer.
AB  - OBJECTIVE: A subset of sporadic colorectal cancers (SCRCs) exhibits
      microsatellite instability (MSI). Most MSI in SCRCs is caused by hMLH1
      inactivation due to promoter methylation. However, the role of MSI in the
      progression of SCRCs remains unclear. METHODS: Thirty-two intramucosal cancers
      and 63 cancers with submucosal invasion were assigned to group 1 (early-stage
      cancer), and 30 Dukes' B and 26 Dukes' C cancers to group 2 (advanced-stage
      cancer). hMLH1 promoter methylation status was determined by methylation-specific
      PCR. MSI was determined using five markers. hMLH1 expression was determined
      immunohistochemically. RESULTS: MSI was found in 1 of 95 (1.1%) tumors in group
      1, compared with 4 of 56 (7.1%) tumors in group 2. In right-sided tumors, the
      overall frequency of hMLH1-methylation-positive tumors in group 1 was not
      significantly different from that in group 2 (17 of 43, 39.5%, vs. 9 of 23,
      39.1%). In right-sided tumors with hMLH1 promoter methylation, the frequency of
      MSI-positive tumors in group 1 was significantly lower than that in group 2 (1 of
      17, 5.9%, vs. 4 of 9, 44.4%, p=0.0081). CONCLUSION: The frequency of MSI caused
      by hMLH1 promoter methylation increases with tumor progression in right-sided
      SCRCs.

PMID- 16293974
TI  - Sequential combination of paclitaxel-carboplatin and paclitaxel-liposomal
      doxorubicin as a first-line treatment in patients with ovarian cancer. A
      multicenter phase II trial.
AB  - Cisplatin or carboplatin plus paclitaxel is considered the standard first-line
      treatment in ovarian cancer. Attempts to maximize tumor cytoreduction with first
      line chemotherapy by incorporating new promising agents led to sequential drug
      administration with two or three doublets. In the present study, we aimed to
      evaluate the activity and the tolerance of two sequential doublets
      (paclitaxel/carboplatin and liposomal doxorubicin/carboplatin) administered as
      first-line treatment in patients with FIGO III/IV ovarian cancer. Treatment
      consisted of four cycles of carboplatin (6 AUC) plus paclitaxel (175 mg/m2; PC
      regimen) followed by four cycles with carboplatin (6 AUC) plus liposomal
      doxorubicin (40 mg/m(2); LD/C regimen) every 3 weeks. Forty-one patients in FIGO
      III or IV were enrolled. In an intention-to-treat analysis, 20 (49%) complete
      (CR) and 12 (29%) partial (PR) responses were achieved (overall response rate,
      ORR: 78%; 95% confidence interval, CI: 64.1-91.9%); with the PC regimen (164
      cycles); 7 (17%) patients have stable (SD) and 2 (5%) progressive (PD) disease.
      The LD/C regimen (124 cycles) was administered in 36 (88%) patients because of 2
      early deaths and 3 patient withdrawals. Three additional patients, 2 with PR and
      1 with SD after PC chemotherapy) achieved a CR. Upon completion of the LD/C
      chemotherapy there were 18 (44%) patients with CR and 9 (22%) with PR (ORR=66%;
      95% CI: 64-92%). The median duration of response was 27 months and the median
      time to progression 20 months. The probability of 2-year survival was 67%. Grade
      3 and 4 neutropenia was observed in 34 and 14.6% of the patients, respectively,
      during the PC regimen, while during the treatment with LD/C the percentages for
      grade 3 and 4 neutropenia were 44.4 and 19.4%, respectively. Febrile neutropenia
      occurred only in patients treated with the PC regimen (4.9%). The incorporation
      of liposomal doxorubicin in this sequential doublet schedule of first-line
      treatment of ovarian carcinoma created a feasible and active regimen. Prospective
      randomized studies are required to assess its efficacy on patient survival.

PMID- 16293976
TI  - Allelic loss at TP53 is not related to p53 protein overexpression in primary
      human endometrial carcinomas.
AB  - We examined loss of heterozygosity (LOH) at the TP53 gene in primary human
      endometrial carcinomas (EC), and investigated the relationship between allelic
      loss, p53 protein overexpression, pRb-1 pathway alterations and MIB-1
      proliferative activity. Applying the non-isotopic PCR-RFLP/VNTR-silver staining
      techniques, we investigated TP53 LOH in 46 tumors at four polymorphic loci. Out
      of 42 informative carcinomas, LOH was found in 19% of the cases studied. In
      general, there was no significant relationship between LOH and the clinical and
      pathological variables of cancer, including patient age, clinical stage,
      histological grade or depth of myometrial invasion. Interestingly, none of 7
      tumors associated with hyperplasia revealed allelic imbalance, whereas 8 of 27
      (30%) tumors without hyperplasia exhibited LOH (p=0.312; Fisher's exact test).
      Overexpression of nuclear p53 was not correlated with allelic loss at TP53
      (p=0.336, Fisher's exact test). It is worth pointing out that p53
      immunoreactivity was significantly related to proliferative activity of cancer
      (R=0.42, p=0.0037; Spearman's rank correlation test). A tendency towards a poorer
      outcome was reported in EC patients displaying TP53 LOH during short-time follow
      up (p=0.093; log-rank test). None of the tumors simultaneously showed LOH at TP53
      and RB1 genes (R=-0.211, p=0.16; Spearman's rank correlation test). p16INK4A
      alterations (LOH and gene deletion) occurred concomitantly, with 3 tumors showing
      the TP53 allelic loss, whereas the cyclin D1/cdk4 complex was overexpressed in a
      case with TP53 LOH. Altogether, losses at TP53 were not associated with p53
      nuclear overexpression, but may affect a subset of EC patients characterized by
      an unfavorable prognosis at short-time follow-up. Allelic loss at TP53 seems to
      arise independently of LOH at the RB1 gene in carcinomas of the uterine corpus in
      humans. Disruptions at p16INK4A and/or cdk4/cyclin D1 concomitantly occurring
      with TP53 LOH may participate in the development of a subset of endometrioid-type
      ECs.

PMID- 16293977
TI  - Effects of corneal thickness, curvature, astigmatism and direction of gaze on
      Goldmann applanation tonometry readings.
AB  - BACKGROUND: The aim of this study was to evaluate the impact of various sources
      of error in Goldmann applanation tonometry (GAT). OBJECTIVES: We evaluated the
      effect of corneal thickness, curvature, astigmatism and direction of gaze as
      sources of error in GAT. METHODS: Orbscan-II (Bausch & Lomb, Inc., Rochester,
      N.Y., USA) examinations were made on 30 healthy subjects and 9 keratoconus
      patients, and the intraocular pressure (IOP) was measured with GAT centrally,
      temporally and inferiorly, with the tonometer prism set horizontally and
      vertically. Orbscan-II images from 50 younger subjects and 49 older subjects were
      analysed retrospectively. RESULTS: IOP was lower on nasal gaze (p = 0.009) but
      higher on upward gaze (p < 0.001) compared with forward gaze. IOP and the corneal
      thickness were independently correlated (R(2) = 0.04; p = 0.003), as were the
      difference in astigmatic vector in the horizontal and vertical meridians and the
      difference in IOP measured with a horizontal and vertical prism (R(2) = 0.17; p <
      0.001). No correlation between IOP and corneal curvature was found. In the
      keratoconus patients, IOPs were generally low, with large astigmatic differences.
      CONCLUSIONS: Corneal thickness, astigmatism and direction of gaze are clinically
      important sources of error in GAT. IOP should preferably be measured with the
      prism both horizontally and vertically. If only one direction is chosen, a
      vertical prism is less sensitive to different directions of gaze. Direction of
      gaze should be carefully monitored, especially in an irregular cornea.

PMID- 16293978
TI  - Platelet activation markers in patients with venous thromboembolism without
      predisposing factors.
AB  - A constant in vitro hypersensitivity of platelets (adenosine diphosphate) has
      been suggested as a risk factor for arterial and even venous thrombosis. Our aim
      was to determine phenotypic and functional alterations of platelets by flow
      cytometry as potential prothrombotic risk factors in patients with a history of
      unexplained spontaneous venous thrombosis. Forty-nine patients with a history of
      spontaneous venous thrombosis and no inherited or acquired thrombophilic risk
      factors were compared with a reference group of 39 healthy volunteers. Flow
      cytometry (FACS) was used to analyze the surface expression of CD62 (P-selectin)
      and CD63 in nonactivated platelets and after in vitro stimulation with adenosine
      diphosphate and thrombin receptor activator peptide 6. Mean fluorescence
      intensity of CD62 and CD63 surface expression as well as percentage of CD62 and
      CD63 positive cells and binding index differed in patients with a history of
      thrombosis compared with the reference group, but failed to reach statistical
      significance. Similar results were observed after in vitrostimulation with
      adenosine diphosphate and thrombin receptor activator peptide 6. In conclusion,
      the expression of CD62 and CD63 of resting and in vitro activated platelets could
      not be established as a risk factor for spontaneous venous thromboembolism.

PMID- 16293979
TI  - Long-term prospective study of recurrent venous thromboembolism in patients
      younger than 50 years.
AB  - Long-term incidence of recurrent venous thromboembolism (VTE) in patients younger
      than 50 years, not affected by a malignancy or chronic diseases, are poorly
      characterized. After the initial episode of VTE and cessation of oral
      anticoagulation, 98 patients, mean age 32.2+/-9.2 years were followed for a
      median of 117 months (range 6-165). Congenital risk factors for VTE were present
      in 36% of patients, acquired persistent (positive antiphospholipid antibodies
      during the whole follow-up) in 19%, and acquired transitory in 44%. Thirty
      episodes of recurrent VTE were documented. The cumulative incidence of VTE after
      1 year of follow-up was 5.1%, 9.8% after 2 years, 14% after 4 years, and 34.2%
      after 8 years. In the univariate analysis, the relative risk of recurrent VTE was
      2.66 [95% confidence interval (CI) 1.03-6.90] for congenital risk factors, 4.97
      (95% CI 1.75-14.0) for persistent acquired (antiphospholipid antibodies), 2.64
      (95% CI 1.23-5.66) for male gender and 2.27(1.00-5.15) for body mass index>30
      kg/m2. In the multivariate analysis, male gender [hazard ratio (HR) 4.23, 95% CI
      1.88-9.77) the presence of congenital factors (HR 3.28, 95% CI 1.25-8.63) and
      acquired persistent factors (HR 8.50, 95% CI 2.84-25.50) were independent risk
      factors for recurrent VTE. In patients under 50 years of age without malignancy
      or underlying chronic disease, hospitalized for an acute thromboembolic event,
      the presence of antiphospholipid antibodies, congenital defects of coagulation,
      male sex, and obesity were risk factors for recurrent VTE. These data raise the
      possibility that selected patients with VTE may require prolonged anticoagulation
      to prevent recurrent disease.

PMID- 16293980
TI  - Association of leukocyte activation, but not the common cold, with restenosis
      after percutaneous coronary intervention in patients with angina pectoris.
AB  - We investigated the relationship between the common cold and restenosis after
      percutaneous coronary intervention (PCI) in Japanese patients with angina
      pectoris, because suffering from a common cold during the follow-up period after
      PCI may be involved in the development of restenosis. In addition, we measured
      the soluble (s) L-selectin level early after PCI in patients with and without
      restenosis. The study group included 104 effort angina pectoris patients. We
      examined whether or not they had had a common cold in the 6 months following
      angioplasty. Finally, 88 patients, whose common cold status was known, were
      selected as the study subjects. Twelve patients caught a common cold after PCI.
      All of these patients were given antibiotics and/or anti-inflammatory agents and
      recovered within 2 weeks. None had clinically detectable influenza infection.
      Thirty-three patients suffered from restenosis and 55 did not. There was no
      significant difference in the restenosis frequency between effort angina pectoris
      patients with and without a common cold. The sL-selectin level was significantly
      increased in patients with restenosis early after PCI, whereas in patients
      without restenosis, sL-selectin remained unchanged. These findings suggest that
      restenosis development after PCI in patients with effort angina pectoris may
      involve leukocyte activation early after PCI, while suffering from a common cold
      during the follow-up period after PCI has no effect.

PMID- 16293981
TI  - Preexisting antibodies to platelet factor 4-heparin complexes in patients with
      acute coronary syndrome who have no history of heparin exposure.
AB  - Preexisting heparin-induced thrombocytopenia (HIT) antibodies are detected in
      some patients who have not previously been exposed to any kind of heparin.
      However, the role of preexisting HIT antibodies in acute coronary syndrome (ACS)
      is still unknown. This study was carried out to clarify the role of preexisting
      HIT antibodies in patients with ACS. Forty patients with ACS who had not been
      exposed to any kind of heparin via the venous or subcutaneous route or heparin
      coated materials and had undergone percutaneous coronary intervention (PCI) under
      heparin anticoagulation within 6 h from the onset of ACS were chosen from the
      medical records in the cardiac emergency department. As a control of the ACS
      patients, 51 patients with angina pectoris who underwent elective PCI under
      heparin anticoagulation were chosen in the same manner as the ACS patients.
      Preexisting HIT antibodies were detected by ELISA in 6 patients. Two of the 6
      patients developed HIT and 1 patient experienced thrombosis requiring
      intracoronary thrombolytic therapy. Thrombotic complications during and
      immediately after PCI in the very early stage after heparin administration were
      found in 4 of 6 patients with preexisting HIT antibodies. The frequency of
      preexisting HIT antibodies in ACS patients was significantly increased in
      comparison with that in non-ACS patients. The odds ratio of the risk of
      thrombotic complication between ACS and non-ACS patients was estimated at 8.82
      (95% CI: 1.3-63). Also, preexisting HIT antibodies in ACS patients significantly
      increased the risk of thrombotic complications compared with ACS without
      preexisting HIT antibodies. In conclusion, ACS patients with positive HIT
      antibodies have an increased risk of thrombotic complications during PCI
      performed under anticoagulation with heparin.

PMID- 16293982
TI  - Evaluation of urokinase-type plasminogen activator and its receptor in neointima
      of polyester vascular grafts.
AB  - The aim of the study was to assess the expression of urokinase-type plasminogen
      activator (uPA) and its receptor (uPAR) in neointima of polyester vascular
      grafts. Anastomotic areas were examined at 1, 4 and 12 months after prosthesis
      implantation in dogs, as well as in human vascular grafts. Immunohistochemistry
      was performed for uPA and uPAR. Graft neointima in dogs was positively stained
      for uPA with increased intensity at 4 and 12 months, whereas uPAR expression
      appeared at 4 and its intensity was increased at 12 months. Intensive uPA and
      positive uPAR labeling was shown in human grafts. The results demonstrated that
      in the early period of the healing process of polyester vascular grafts only uPA
      is present in the neointima in the region of the graft to adjacent artery
      anastomosis, whereas in healed grafts in dogs and humans uPAR is found as well.

PMID- 16293983
TI  - Platelet aggregation in portal hypertension and its modification by ultra-low
      doses of aspirin.
AB  - Aspirin (ASA) is widely accepted as antithrombotic drug, but several reports
      point out that its use in ultra-low doses (ULD) has prothrombotic properties. In
      this study, we evaluate the effect of portal hypertension in rats on platelet
      aggregation in an in vivo arterial thrombosis model induced by a laser beam.
      Portal hypertension was produced by calibrated stenosis of the portal vein. ASA
      in ULD was injected to both control and portal hypertensive groups. Platelet
      aggregation induced by ADP, prothrombin time, activated partial thromboplastin
      time, fibrinogen and induced hemorrhagic time test were also performed. Portal
      hypertensive rats showed a diminished number of emboli and duration of
      embolization in the laser procedure and an increase in induced hemorrhagic time.
      These changes were reverted by one injection of ASA at ULD. This observation
      could be of importance for primary prevention or the treatment of recurrence in
      upper digestive tract hemorrhage in portal hypertensive patients.

PMID- 16293984
TI  - Platelets treated with ticlopidine are less reactive to unusually large von
      Willebrand factor multimers than are those treated with aspirin under high shear
      stress.
AB  - Much attention has recently been focused on the interaction between unusually
      large von Willebrand factor multimers (UL-VWFM) and platelets under high shear
      stress in pathological thrombus formation. The antiplatelet drugs acetylsalicylic
      acid (aspirin) and a thienopyridine derivative (ticlopidine) are commonly used to
      treat cerebral ischemia but exert different effects on high-shear-stress-induced
      platelet aggregation (H-SIPA) in the plasma. To examine the effects of these
      drugs in the absence of plasma factors, we studied H-SIPA using washed platelets
      (WPs) and purified UL-VWFM. WPs were prepared from the blood of 9 aspirin-treated
      and 11 ticlopidine-treated patients with cerebral ischemia, and H-SIPA in the
      presence of UL-VWFM was measured using a cone plate aggregometer. Plasma levels
      of VWF antigen with its multimer analysis, ristocetin cofactor and VWF-cleaving
      protease (ADAMTS13) activity were also measured. Forty-six healthy volunteers
      from 2 age groups, 20-40 years (n=20) and 41-60 years old (n=26), were also
      tested as controls. H-SIPA was significantly inhibited for ticlopidine-treated
      platelets, but it was observed to a lesser extent for aspirin-treated platelets.
      For both groups, no difference in the plasma levels of VWF antigen, ristocetin
      cofactor and ADAMTS13 activity was noted. All patients possessed UL-VWFM, and it
      was detected in healthy volunteers with increasing frequency with increasing age.
      Under plasma-free conditions, platelets from aspirin-treated patients exhibit
      marginal but significant inhibition of H-SIPA. Furthermore, the presence of UL
      VWFM in the plasma of patients and normal volunteers is directly related to their
      age rather than being a consequence of underlying disease.

PMID- 16293985
TI  - Inhibition of thrombin-induced vascular endothelial growth factor production in
      human neuroblastoma (NB-1) cells by argatroban.
AB  - Thrombin, a serine protease that plays a pivotal role in blood coagulation, wound
      healing, and angiogenesis, has also been implicated in the mitogenesis of various
      cell types. Previously, we showed that thrombin and the thrombin receptor agonist
      peptide (TRAP-14; SFLLRNPNDKYEPF) for protease-activated receptor 1 (PAR1) induce
      vascular endothelial growth factor (VEGF) secretion in PC-12 cells. In this
      study, we show that thrombin and TRAP-14 also stimulate VEGF secretion in the
      human NB-1 neuroblastoma cells. In these cells, we further show that thrombin
      induced VEGF secretion was blocked by cycloheximide and actinomycin D, indicating
      that de novo protein synthesis is essential for this process. Reduced thrombin
      induced VEGF secretion upon treatment with LY294002, calphostin C, or BAPTA,
      further suggests that the process is dependent on phosphatidyl-inositol-3-kinase,
      protein kinase C, and calcium. However, the complete loss of thrombin-induced
      VEGF production upon treatment with argatroban, a derivative of arginine and a
      potent anticoagulant/antithrombin agent, supports the notion that argatroban
      serves as a useful therapeutic tool for thrombin-associated pathologic
      conditions. Here, it appears that argatroban may be effective in controlling
      disorders linked to thrombin-induced VEGF production in neuronal cells.

PMID- 16293986
TI  - Acute myocardial infarction with lung cancer during treatment with gefitinib: the
      possibility of gefitinib-induced thrombosis.

PMID- 16293987
TI  - Changes of gastrointestinal argyrophil endocrine cells in the COLO205 tumor
      implanted Balb/c-nu/nu mice.
AB  - The regional distributions and frequencies of argyrophil endocrine cells in
      gastrointestinal (GI) tract of Balb/c-nu/ nu mouse were studied using Grimelius
      silver stain after abdominal subcutaneous implantation of COLO205. The
      experimental animals were divided into two groups, one is non-implanted group
      (Sham) and the other is COLO205- implanted group. Samples were collected from GI
      tract (fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum) at 21
      days after implantation of COLO205 cells (1 x 10(6) cell/mouse). In this study,
      argyrophil cells were detected throughout the entire GI tract with various
      frequencies regardless of implantation. Most of these argyrophil cells in the
      mucosa of GI tract were generally spherical or spindle in shape (open type cell)
      while cells showing round in shape (close type cell) were found occasionally in
      gastric and/or intestinal gland regions. The regional distributions of argyrophil
      cells in COLO205 were similar to those of Sham. However, significant decreases of
      argyrophil cells were detected in COLO205 compared to those of Sham except for
      the jejunum and ileum. In the jejunum and ileum, argyrophil cells in COLO205
      showed similar frequencies compared to those of Sham. In the pylorus, the most
      dramatically decreasement of argyrophil cells were detected in COLO205 compared
      to that of Sham. Implantation of COLO205 tumor cell line induced severe
      quantitative changes of argyrophil cell density, and the abnormality in density
      of GI endocrine cells may contribute to the development of gastrointestinal
      symptoms such as anorexia and indigestion, frequently encountered in patients
      with cancer.

PMID- 16293988
TI  - Studies on sodium and potassium metabolism and subsequent influence on
      electrocardiogram in unilaterally adrenalectomized black Bengal goat (Capra
      hircus).
AB  - Unilateral adrenalectomy was performed in six black Bengal goat (Capra hircus)to
      study electrocardiograph in connection with mineral metabolism with special
      reference to sodium and potassium and some other factors of physiological
      importance. The parameters were studied at every 12 hrs interval upto 120 hrs and
      24 hrs interval from 120 to 240 hrs. Physiological parameters, like body weight
      and rectal temperature, changed non-significantly (p < 0.05) after adrenalectomy.
      Among minerals, plasma sodium (p < 0.01) and plasma potassium (p < 0.05)
      concentration were changed significantly between hours leaving impression in ECG
      as widening of QRS complex and peaked T wave with increased amplitude found after
      unilateral adrenalectomy. Heart rate also increased significantly (p < 0.01)
      between hours.

PMID- 16293990
TI  - Red blood cell elution time of strains of Newcastle disease virus.
AB  - Elution time of velogenic, mesogenic and lentogenic strains of Newcastle disease
      virus was determined. The differences in their elution time were also calculated.
      Four samples, each of a velogenic strain (VGF2), a mesogenic strain (Komarov) and
      a lentogenic strain (LaSota) were used for hemagglutination test with 0.6%
      chicken red blood cells. The time it took for wells of the end hemagglutination
      points (highest dilution that gave agglutination) to elute was recorded as
      elution time for each sample. The mean elution time of the three strains of
      Newcastle disease virus differed significantly (p < 0.05). The velogenic strain
      gave the highest mean elution time of 118 min, followed by the mesogenic strain
      with 59 min and the lentogenic strain with 25 min. Based on this result it
      appears that elution time could form a basis for rough characterization of
      isolates of Newcastle disease virus into the three major strains.

PMID- 16293989
TI  - Comparative evaluation of phenobarbital-induced CYP3A and CYP2H1 gene expression
      by quantitative RT-PCR in Bantam, Bantamized White Leghorn and White Leghorn
      chicks.
AB  - The present work was to study induction of cytochrome P450 (CYP)3A and CYP2H1
      gene by reverse transcriptase polymerase chain reaction (RT-PCR) and quantitative
      RTPCR in Bantam, Bantamized White Leghorn and White Leghorn chicks. Out of 18
      chicks total 3 from each group (Bantam, Bantamized White Leghorn and White
      Leghorn) were treated intraperitoneal with phenobarbital at the dose rate of 12
      mg/100 g (body weight) while the control group was treated with the saline. Total
      RNA was extracted from the liver samples using Tri Reagent based method. First
      strand cDNA was synthesized using one step RT-PCR kit. The PCR was performed and
      the product was subjected to agarose gel electrophoresis. Quantitative RT-PCR was
      conducted to quantify gene expression level of CYP3A and CYP2H1 genes. Relative
      expression ratio of CYP3A and CYP2H1 genes was calculated using relative
      expression software tool (REST). It was found that CYP3A is up regulated by
      factor of 1.34, 14.51 and 1.00 in Bantam, Bantamized White Leghorn and White
      Leghorn chicks, respectively. In Bantam and Bantamized White Leghorn chicks
      CYP2H1 gene was up regulated by factor 1.50 and 80.87, respectively but down
      regulated by a factor of 1.97 in White Leghorn chicks. The PCR efficiency ranged
      from 1.30 to 1.70, 0.86 to 1.70 and 0.91 to 1.58 for CYP3A, CYP2H1 and beta
      actin, respectively in Bantam, Bantamized White Leghorn and White Leghorn chicks.

PMID- 16293991
TI  - Prevalence of Lawsonia intracellularis, Brachyspira hyodysenteriae and Salmonella
      in swine herds.
AB  - The prevalence of Lawsonia intracellularis, Brachyspira hyodysenteriae and
      Salmonella spp. were investigated by multiplex PCR using fecal samples of pigs
      with diarrhea or a history of diarrhea. The overall herd prevalence of L.
      intracellularis, B. hyodysenteriae and Salmonella spp. were 46.5%, 37.2% and
      51.1%, respectively. Also, the prevalence of L. intracellularis, B.
      hyodysenteriae and Salmonella spp. among all sampled pigs were 19.9%, 10.8% and
      17.7%, respectively. Seventeen of 43 herds were positive with 2 enteric
      organisms, and 2 herds were positive with L. intracellularis, B. hyodysenteriae
      and Salmonella spp. simultaneously. It was notable that 11 of 12 herds with more
      than 2,000 pigs were affected with Salmonella spp., and that only 2 of 12 the
      herds were affected with B. hyodysenteriae. This study suggested that herds
      positive for L. intracellularis, B. hyodysenteriae and Salmonella spp. were
      distributed throughout Korea, although the relationship among other pathogens
      such as viral or parasitic ones and/or with metabolic disorders was not
      determined.

PMID- 16293992
TI  - Analysis of normal electrocardiograms of Jamunapari goats.
AB  - In the present study, the normal electrocardiographic (ECG) values in the adult
      male Jamunapari breed of the goats were described. The mean heart rate in the
      goats was 127 +/- 3.46 per minute and ranged 107 and 168. The amplitudes and
      duration of various waveforms of ECG for six standard limb leads (I, II, III,
      aVL, aVR and aVF) were estimated. The overall P, QRS and T amplitudes
      (millivolts) were 0.065 +/- 0.01, 0.47 +/- 0.06 and 0.20 +/- 0.014 respectively.
      The duration (seconds) of these wave forms were 0.042 +/- 0.005, 0.033 +/- 0.002
      and 0.10 +/- 0.014, respectively. The P-R interval and R-R intervals ranged
      between 0.06- 0.14 and 0.40-0.58 respectively. The average Q-T interval was 0.24
      +/- 0.01 second, indicating the time for which the caprine ventricle remained
      depolarized. The corrected QT interval was also calculated which was found to
      vary from 0.24 to 0.57. The mean frontal plane vectors for the wave forms P, QRS
      and T wave forms were +49.99 +/- 6.02, +37.34 +/- 4.05 and +52.26 +/- 6.79
      degrees respectively.

PMID- 16293993
TI  - Validation of an electrometric blood cholinesterase measurement in goats.
AB  - A modified electrometric method was described and validated for measurement of
      plasma and erythrocyte cholinesterase activities in 6-18 months old goats. The
      enzymatic reaction mixture contained 3 ml distilled water, 3 ml barbital
      phosphate buffer (pH 8.1), 0.2 ml plasma or erythrocytes and 0.1 ml
      acetylthiocholine iodide (7.5%) as a substrate. The mixture was incubated at 37
      degrees C for 40 minutes. The pH of the reaction mixture was determined by a pH
      meter before and after the incubation. The initial pH was measured before the
      substrate addition. The enzyme activity was expressed as DeltapH/40 min. The
      coefficients of variation of the described method in measuring plasma and
      erythrocyte cholinesterase activities were 4 and 2%, respectively. Preliminary
      reference values (n = 14) of the mean cholinesterase activity (DeltapH/40 min)
      and 95% confidence interval in the plasma were 0.194 and 0.184-0.204,
      respectively, and those of the erythrocytes were 0.416 and 0.396-0.436,
      respectively. The pseudocholinesterase activity of the plasma cholinesterase was
      63.5% as determined by quinidine sulfate inhibition. The organophosphorus
      insecticides dichlorvos and diazinon at 0.5-4 microM and the carbamate
      insecticide carbaryl at 5-20 microM in the reaction mixture significantly
      inhibited plasma (13.7-85.5%) and erythrocyte (16.4-71.9%) cholinesterases in
      vitro in a concentration-dependent manner. The results suggest that the described
      electrometric method is simple, precise and efficient in measuring blood
      cholinesterase activity in goats.

PMID- 16293995
TI  - Primary survey of avian influenza virus and Newcastle disease virus infection in
      wild birds in some areas of Heilongjiang Province, China.
AB  - Two hundred thirty specimens of wild birds were collected from some areas in
      Heilongjiang Province during the period of 2003-2004, including two batches of
      specimens collected randomly from a same flock of mallards in Zhalong Natural
      Reserve in August and December, 2004, respectively. Primary virus isolation and
      identification for avian influenza virus (AIV) and Newcastle disease virus (NDV)
      were performed. The results showed that only two specimens of young mallards
      collected from Zhalong Natural Reserve in August, 2004 were positive to AIV
      (isolation rate 0.9%), and one strain (D57) of these two virus isolates was
      identified to be H9 subtype by hemagglutination inhibition test. Meanwhile, the
      two batches of blood serum samples of mallards from Zhalong were also examined
      for antibodies against AIV and NDV. Among 38 blood serum samples collected in
      August, antibodies against the hemagglutinin of H1, H3, H5, H6 and H9 subtypes of
      AIV were found in 1, 0, 2, 0 and 8 samples, respectively; and 11 samples were
      found with antibody against NDV. Whereas the NDV isolation in both two batches of
      specimens of mallard was negative, all of the 32 blood serum samples collected in
      December were negative for antibodies against AIV and NDV.

PMID- 16293994
TI  - A predictive model for the level of sIgA based on IgG levels following the oral
      administration of antigens expressed in Saccharomyces cerevisiae.
AB  - Oral vaccination may be the most efficient way of inducing an immune response at
      the remote mucosal site through the common mucosal immune network. Antigen
      specific secretory IgA (sIgA) is the major immunoglobulin type generally detected
      in the secretions of experimental animals following an effective oral
      immunization. Actinobacillus pleuropneumoniae causing disease in the lung of pig
      initially interacts, colonizes, and infects the host tissues at the mucosal
      surface of the respiratory tract. Also, importantly for A. pleuropneumoniae
      protection, the quantity of sIgA in the lung had merits associated with the
      mucosal immunity. However, there is no simple method to monitor the level of sIgA
      as an indicator for the induction of local immune responses by an oral
      vaccination in the target tissue. Therefore, the relationship between sIgA and
      IgG was analyzed to evaluate the induction of local immune responses by an oral
      immunization with Saccharomyces cerevisiae expressing the apxIA and apxIIA genes
      of A. pleuropneumoniae in this study. The correlation coefficient of
      determination (r2 x 100) for paired samples in both vaccinated and control groups
      showed a significant positive-relationship between IgG in sera and sIgA in the
      lung or intestine. These results indicated that IgG antibody titers in sera could
      be useful to indirectly predict local immune response, and sIgA, in the lung or
      intestine to evaluate the efficacy of an oral vaccination.

PMID- 16293996
TI  - Development of synthetic peptide ELISA based on nonstructural protein 2C of foot
      and mouth disease virus.
AB  - It was reported that the sera of convalescent animals contain antibodies to foot
      and mouth disease (FMD) virus (FMDV) 2C, highly conserved nonstructural protein
      (NSP), whereas the sera of vaccinated animals do not. But ELISA methods using
      this protein were not reported and developed until recently. In this study, NSP
      2C peptides were synthesized within the amino acid sequence of the conserved 2C
      nonstructural region of FMDV according to the sequences from Genbank database and
      used for identifying antigenic determinants. One of the synthesized thirteen
      peptides gave strong positive reactivity with most of the sera from 13 FMD
      infected farms, but not with sera from vaccinated and non-infected animals.
      Moreover, with the sera collected through serial bleedings from four cattle and
      five goats infected with FMDV O/SKR/2000 experimentally, positive results were
      obtained in two species after 10 days post infection (DPI). Therefore, we tried
      to develop and evaluate this ELISA based on 2C peptides. In comparison with the
      commercial NSP ELISA, the 2C peptide based ELISA method showed good specificity
      and sensitivity. These results demonstrate that the synthetic 2C peptide ELISA
      can be a complementary marker to differentiate FMDV-infected from vaccinated on a
      herd basis.

PMID- 16293998
TI  - Characterization of Brachyspira hyodysenteriae isolates from Korea.
AB  - This study was done to characterize diversity in 10 Brachyspira hyodysenteriae
      isolates in Korea. The isolates were compared with 14 well-characterized non
      Korean strains of various Brachyspira species. All Korean isolates showed strong
      beta haemolysis and had blunt cell ends with 7-14 periplasmic flagella. They
      produced indole, and did not ferment fructose. They were alpha-glucosidase
      positive and alpha-galatosidase negative using the APIZYM kit. Using polyclonal
      antisera raised in rabbits against recognized serotypes, all isolates showed a
      strong reaction to B. hyodysenteriae antisera E, A and B. Using multilocus enzyme
      electrophoresis (MLEE) with 15 enzymes and 5 buffer systems, the Korean and non
      Korean isolates were divided into 22 electrophoretic types (ETs) and 5 divisions
      (A, B, C, D and E). Division A corresponded to B. hyodysenteriae, B to B.
      innocens, C to B. intermedia, D to B. murdochii and E to B. pilosicoli. The 10
      Korean isolates of B. hyodysenteriae were relatively diverse, being divided into
      9 ETs within MLEE division A. They were all distinct from the non-Korean strains.

PMID- 16293997
TI  - Detection of Bartonella species from ticks, mites and small mammals in Korea.
AB  - We investigated the prevalence of Bartonella infections in ticks, mites and small
      mammals (rodents, insectivores and weasels) collected during 2001 through 2004,
      from various military installations and training sites in Korea, using PCR and
      sequence analysis of 16S rRNA, 23S rRNA and groEL heat shock protein genes. The
      prevalence of Bartonella spp. was 5.2% (n = 1,305 sample pools) in ticks, 19.1%
      (n = 21) in mesostigmatid mites and 13.7% (n = 424 individuals) in small mammals.
      The prevalence within the family Ixodidae was, 4.4% (n = 1,173) in Haemaphysalis
      longicornis (scrub tick), 2.7% (n = 74) in H. flava, 5.0% (n = 20) in Ixodes
      nipponensis, 11.1% (n = 9) in I. turdus, 33.3% (n = 3) in I. persulcatus and
      42.3% (n = 26) in Ixodes spp. ticks. In rodents, the prevalence rate was, 6.7% (n
      = 373) in Apodemus agrarius (striped field mouse) and 11.1% (n = 9) in Eothenomys
      regulus (Korean red-backed vole) and in an insectivore,Crocidura lasiura, 12.1%
      (n = 33). Neither of the two weasels were positive for Bartonella spp.
      Phylogenetic analysis based on amino acid sequence of a portion of the groEL gene
      amplified from one A. agrarius spleen was identical to B. elizabethae species. We
      demonstrated the presence of Bartonella DNA in H. longicornis, H. flava and I.
      nipponensis ticks, indicating that these ticks should be added to the growing
      list of potential tick vectors and warrants further detailed investigations to
      disclose their possible roles in Bartonella infection cycles.

PMID- 16293999
TI  - CT myelography of the thoraco-lumbar spine in 8 dogs with degenerative
      myelopathy.
AB  - CT myelography of the T11-L2 region was performed in 8 large-breed dogs with a
      clinical diagnosis of degenerative myelopathy (DM) and 3 large-breed dogs that
      were clinically normal. CT myelographic characteristics were recorded for each
      dog, at each disc level. Area measurements of the spinal cord, dural sac,
      vertebral canal, and vertebral body were recorded at 4 slice locations for each
      disc level. Mean area ratios were calculated and graphically compared, by slice
      location and group. In all dogs, CT myelography identified morphologic
      abnormalities that were not suspected from conventional myelograms.
      Characteristics observed with higher frequency in DM versus normal dogs were:
      spinal stenosis, disc protrusion, focal attenuation of the subarachnoid space,
      spinal cord deformity, small spinal cord, and paraspinal muscle atrophy. Mean
      spinal cord:dural sac, spinal cord:vertebral canal, dural sac: vertebral canal,
      and vertebral canal:vertebral body ratios were smaller in DM versus normal dogs
      at more than one disc level. Some CT myelographic characteristics in DM dogs were
      similar to those previously reported in humans, dogs and horses with stenotic
      myelopathy.

PMID- 16294000
TI  - Comparison of an enzyme-linked immunosorbent assay with serum neutralization test
      for serodiagnosis of porcine epidemic diarrhea virus infection.
AB  - An indirect porcine epidemic diarrhea (PED) virus (PEDV) enzyme-linked
      immunosorbent assay (ELISA) was compared with the serum neutralization (SN) test
      by testing 46 samples from experimentally infected sows, 73 samples from naive
      sows, and 1,024 field sow samples from 48 commercial swine farms of undefined PED
      status. The SN test and the ELISA were performed using PEDV, KPEDV-9 strain.
      Viral proteins as a coating antigen of PEDV ELISA were extracted from the
      cytoplasm of PEDV-infected Vero cells using a non-ionic detergent, Triton X-100,
      and a simple protocol of PEDV ELISA was followed. The presence of antibodies in
      these experimental samples was confirmed by SN and ELISA in which the sensitivity
      of the ELISA was 89.1%, and the corresponding specificity was 94.5%. On testing
      1,024 field samples, an overall agreement of 84.2% was generated between the SN
      and ELISA. This study demonstrates that the PEDV ELISA is a useful serodiagnostic
      screening test at herd level for detecting swine antibodies against PEDV.

PMID- 16294001
TI  - The anti-thrombotic activity of surfactins.
AB  - Platelet aggregation was inhibited and the density of platelet-rich plasma (PRP)
      clots was decreased by the preincubation of PRP with surfactins, an acidic
      lipopeptide of Bacillus subtilis complex BC1212 isolated from soybean paste, in
      dose-dependent manner. Our findings suggest that surfactins are able to prevent a
      platelet aggregation leading to an inhibition of additional fibrin clot
      formation, and to enhance fibrinolysis with facilitated diffusion of fibrinolytic
      agents.

PMID- 16294002
TI  - Experimental reproduction of proliferative enteropathy and the role of IFN-gamma
      in protective immunity against Lawsonia intracellularis in mice.
AB  - Proliferative enteropathy was reproduced in IFN-gamma receptor knockout (IFN
      gamma R-) mice by experimental infection with Lawsonia intracellularis (L.
      intracellularis). The cecum and the colon of the infected mice were evidently
      enlarged 2 weeks post infection. The presence of L. intracellularis was
      identified in the stool and the cecum of the mice after infection. However, high
      levels of IFN-gamma were detected in the sera of the infected mice 2 weeks PI.
      These data indicated that the IFN-gamma produced in the infected mice should have
      been utilized by it's receptor to elicit protective immune responses against L.
      intracellularis infections.

PMID- 16294003
TI  - A Case of oculocutaneous albinism in a Maltese.
AB  - A 4-month-old female maltese dog was admitted to Veterinary Medical Teaching
      Hospital of Seoul National University for evaluation of abnormal color of
      bilateral irises. This patient had the photophobia in the light and exhibited the
      complete absence of pigment resulting in white hair, pink muzzle, eyelids and
      foot-pads. Central zone of the irises were yellow in color influenced by tapetal
      reflex, and peripheral zone were pale blue. The iridal capillaries were
      transparented on the irises. Ophthalmoscopic examination revealed a yellow
      tapetal fundus but no pigment in the nontapetal fundus.

PMID- 16294004
TI  - A case of adrenal gland dependent hyperadrenocorticism with mitotane therapy in a
      Yorkshire terrier dog.
AB  - Hyperadrenocorticism, a disorder characterized by excessive production of
      cortisol by the adrenal cortex, is well-recognized in dogs. A 10-year-old, intact
      male, Yorkshire terrier dog was evaluated because of corneal ulceration and
      generalized alopecia. Diagnosis was made based on history taking, clinical signs,
      physical examination, and results of routine laboratory testing (complete blood
      count, serum biochemical analysis, and urinalysis). In addition,
      adrenocorticotropic hormone (ACTH) stimulation test and abdominal ultrasonography
      were also used to diagnose this case. The patient was diagnosed as adrenal gland
      neoplasia and medical therapy using the adrenocorticolytic agent, mitotane, was
      initiated. An ACTH stimulation test was performed after initial therapy. After
      successful induction was obtained, maintenance therapy with mitotane still
      continued.

PMID- 16294005
TI  - Recent footrot outbreak in Debrezeit swine farm, central Ethiopia.
AB  - An outbreak of footrot has occurred in Debrezeit swine farm that is located 44 km
      south east of the capital. Among 24 pigs, 75% showed lameness, hot, painful and
      swollen feet, hemorrhagic bruising of the coronary band, heel erosion, sole
      ulcers and separation of skin from hoof on hind limbs. Bacteriological
      examination of the specimen from the affected limbs has shown the involvement of
      Staphylococcus, Streptococcus and Dichelobacter nodosus. The overt clinical
      lameness and inability to stand or mount can cause reduced reproductive
      performance. This preliminary finding thus warrants further epidemiological
      investigation.

PMID- 16294006
TI  - Surgical correction of corneal dermoid in a dog.
AB  - A five-month-old female Shih-tzu puppy was presented for repair of congenital
      choristoma in left eye. The patient was suffered from chronic epiphora and ocular
      discharge during 3 months. On ophthalmic examination, left eye revealed hyperemia
      in conjunctiva of the temporal canthus due to choristoma with hair. At surgery,
      the choristoma invaded by stromal layer of the cornea, and extended to limbus and
      conjunctiva. Based on the anatomical location and histopathological features of
      the removed tissue, the choristoma was diagnosed as corneal dermoid.

PMID- 16294007
TI  - 2:1 Stoichiometry of the CED-4-CED-9 complex and the tetrameric CED-4: insights
      into the regulation of CED-3 activation.
AB  - Four evolutionally conserved proteins -EGL-1, CED-9, CED-4 and CED-3-
      collectively control the initiation of programmed cell death (PCD) in
      Caenorhabditis elegans. Activation of CED-3, the cell killing caspase, requires
      CED-4. The pro-death function of CED-4 is inhibited by the mitochondria-bound CED
      9. Crystal structure of the 150-kDa CED-4-CED-9 complex at 2.6 A resolution
      reveals a 2:1 stoichiometry between CED-4 and CED-9. EGL-1 binding to CED-9
      results in the dissociation of CED-4 from the CED-4-CED-9 complex. The freed CED
      4 dimer further dimerizes to form a tetramer. Only the CED-4 tetramer, but not
      dimer or monomer, is capable of activating CED-3. Thus, CED-9 inhibits CED-4
      mediated activation of CED-3 by sequestering CED-4 dimer from further
      dimerization. On the basis of structural and biochemical analyses, working models
      are proposed to explain the mechanism by which CED-4 facilitates CED-3
      activation.

PMID- 16294008
TI  - Distinct specificities of pRb phosphorylation by CDK4 activated by cyclin D1 or
      cyclin D3: differential involvement in the distinct mitogenic modes of thyroid
      epithelial cells.
AB  - Two distinct mitogenic modes coexist in the physiologically relevant model of
      primary cultures of dog thyroid epithelial cells. The differentiation-associated
      mitogenic stimulation by TSH and cAMP specifically requires the assembly and
      activation of cyclin D3-cyclin-dependent kinase (CDK)4 associated to p27(kip1),
      while the dedifferentiating proliferation induced by growth factors is associated
      with induction of cyclin D1. Here, we suggest that the related CDK "inhibitors"
      p21(cip1) and p27 are differentially utilized as positive CDK4 regulators in
      these mitogenic stimulations. p21 was induced by EGF + serum, but repressed by
      TSH, which, as previously shown, upregulates p27. In response to EGF + serum, p21
      supported the nuclear localization, phosphorylation and pRb-kinase activity of
      CDK4. Unexpectedly, partly different site-specificities of pRb-kinase activity,
      leading to similar differences in the phosphorylation pattern of pRb in intact
      cells, were associated with cyclin D3-CDK4 bound to p27 in TSH-stimulated cells,
      or with CDK4 bound to p21 in growth factor-stimulated cells. These differences
      were ascribed to the predominant association of the latter complex to cyclin D1.
      Indeed, in different cell types and species, cyclin D1 varied from cyclin D3 by
      more efficiently driving the phosphorylation of pRb at sites (Ser807/811 and
      Thr826) required for its electrophoretic mobility shift. Therefore, different D
      type cyclins could differently impact some pRb functions, which should be
      considered not only in the understanding of the relationships between cell cycle
      and differentiation expression in the distinct mitogenic modes of thyroid cells,
      but also in various development or differentiation models associated with
      dramatic switches in the expression of individual D-type cyclins.

PMID- 16294010
TI  - Cooperation of EB1-Mal3 and the Bub1 spindle checkpoint.
AB  - EB1 is a conserved microtubule binding protein that preferentially localizes to
      the growing tips of the microtubule plus end. Whilst the function of EB1 in cell
      polarity control is well established, its role during mitosis remains largely
      elusive. Here we discuss our recent work of roles for Mal3, the fission yeast EB1
      homologue, in mitotic progression and chromosome stability. Our analysis sheds
      light upon the requirement of Mal3 for bipolar microtubule attachment and its
      cooperative role with the spindle assembly checkpoint. In particular Mal3
      collaborates with a specific branch of this checkpoint pathway, which is
      dependent upon Bub1, but not Mad2. As malfunctioning of the EB1-mediated pathway
      might be directly related to chromosome instability in some types of human
      cancers, a new knowledge of Mal3's mitotic role would be of direct relevance to
      understanding the molecular defects in these cancer cells.

PMID- 16294009
TI  - Resistance to microtubule-stabilizing drugs involves two events: beta-tubulin
      mutation in one allele followed by loss of the second allele.
AB  - Resistance to Taxol (paclitaxel) or the epothilones (Epo) occurs via the
      acquisition of point mutations in beta-tubulin residues important for drug
      tubulin binding. We have isolated four drug-resistant clones selected with Taxol
      or Epo A, which harbor distinct beta-tubulin mutations. During the development of
      a stable drug-resistant phenotype, early clones expressing both wild-type (wt)
      and mutant beta-tubulin sequences exhibited a 10-fold drug resistance, while more
      advanced clones expressing only the mutant beta-tubulin sequence exhibited 30 to
      50-fold drug resistance. The drug-sensitive parental 1A9 ovarian carcinoma cell
      line and the drug resistant clones (1A9-A8, 1A9-PTX10 and 1A9-PTX22) were
      evaluated for loss of heterozygosity (LOH) for beta-tubulin (6p25) by single
      nucleotide polymorphism (SNP) and fluorescent in situ hybridization (FISH)
      analyses. Functional assays such as drug-induced tubulin polymerization, cell
      cycle analysis by FACS, DNA sequencing for beta-tubulin and mitotic index by
      immunofluorescence were performed to correlate the beta-tubulin LOH status with
      drug response in the early- and late-step drug-resistant clones. Late-step drug
      resistant clones revealed LOH in one allele for wt beta-tubulin in addition to a
      beta-tubulin mutation in the other allele leading to increased levels of drug
      resistance, while the early-step clones that contained both a wt and a mutant
      beta-tubulin allele were considerably less drug resistant. The LOH and functional
      assays revealed cell response that was proportional to the tubulin gene and
      heterozygosity status. Acquired tubulin mutations in conjunction with LOH for the
      wt tubulin resulted in a highly resistant phenotype, revealing a new mechanism
      for taxane resistance.

PMID- 16294011
TI  - Constitutively active Cdc42 mutant confers growth disadvantage in cell
      transformation.
AB  - The Rho family small GTPase Cdc42 is critical for diverse cellular functions
      including the regulation of actin organization, cell polarity, intracellular
      membrane trafficking, transcription, cell cycle progression and cell
      transformation. Like other members of the Rho family, Cdc42 cycles between the
      GTP-bound, active state, and the inactive, GDP-bound state under tight
      regulation, and it is believed that the GTP bound form of Cdc42 represents the
      active signaling module in eliciting effector activation and cellular responses.
      The constitutively active mutant, V12, derived from the analogous mutations found
      in oncogenic Ras that are GTPase-defective, and a "fast-cycling" self-activating
      mutant, F28, of Cdc42, have been widely in use to study the cellular effects of
      Cdc42. Here we report that the constitutively active V12 mutant of Cdc42, when
      stably expressed in cells, could behave in a dominant negative fashion in
      inhibiting cell proliferation while the F28 mutant was growth stimulatory. The
      V12 mutant failed to transform NIH3T3 cells while F28 potently stimulated
      anchorage-independent growth. The growth inhibitory effect of the V12 mutant
      correlated with activation of JNK2 and suppression of the cyclin D1 and NF-kappaB
      expressions that were instead upregulated by the F28 mutant. Furthermore, the V12
      mutant could suppress, whereas the F28 mutant potentiated or had no effect on, a
      wide variety of oncogene-induced cell transformation, including that by the Dbl
      family GEFs Dbl, Vav and Lbc and the oncogenic Ras, ErbB-2, PDGF B or Raf. These
      results raise the possibility that over-saturation or constitutive activation of
      Cdc42 signal may negatively impact on cell proliferation and that both the
      activation and deactivation steps, or the complete GTPase cycle, of Cdc42 is
      required for proper function.

PMID- 16294012
TI  - SUMO keeps a check on recombination during DNA replication.
AB  - The small ubiquitin-related modifier SUMO plays an important role in the
      maintenance of genome stability. Accordingly, DNA replication, repair and
      recombination factors as well as mediators of chromosome dynamics and cohesion
      are among its many targets. Attachment of SUMO can modulate the properties of the
      modified proteins by affecting localization, conformation, stability or enzymatic
      activity, but often its mechanism of action remains poorly defined. Recent
      findings demonstrate how SUMO modification of PCNA, the processivity clamp for
      replicative DNA polymerases, prevents unscheduled recombination during DNA
      replication by means of directly enhancing physical interactions with an anti
      recombinogenic helicase, Srs2. This review highlights how the SUMO conjugation
      system exerts its effect on the replication fork and discusses the implications
      for ubiquitin-dependent DNA damage tolerance.

PMID- 16294013
TI  - Histone deacetylase inhibition induces apoptosis in neuroblastoma.
AB  - Histone deacetylase inhibitors constitute a promising new treatment for cancer
      due to their novel site of action and low toxicity. Almost all histone
      deacetylase inhibitors currently in clinical development have anti-proliferate
      activities against cells in cultures, and specifically cause cell cycle arrest,
      differentiation and apoptosis. Interestingly, despite their rapid advance into
      clinical use, the cellular responses leading to these effects remain unclear. We
      recently reported that histone deacetylase inhibitor treatment induces apoptosis
      of neuroblastoma cells by increasing the acetylation of Ku70 in the cytoplasm,
      resulting in the release of Bax from Ku70. Subsequently, Bax releases cytochrome
      c from mitochondria causing apoptosis. Here we will discuss these findings and
      the implications of our model for the further clinical development of histone
      deacetylase inhibitors in the treatment of cancer.

PMID- 16294014
TI  - Ras-Raf signaling needs prohibitin.
AB  - Prohibitin has been connected to diverse cellular functions including cell cycle
      control, senescence, apoptosis and stabilization of mitochondrial proteins. By
      employing a loss of function approach using siRNAs we have demonstrated an
      unexpected role of PHB in the activation of Raf/MEK/ERK pathway by active Ras and
      in modulating epithelial cell adhesion and migration. PHB directly interacts with
      C-Raf and is required for the displacement of 14-3-3 from C-Raf by active Ras to
      facilitate plasma membrane localization and activation. Further, the adherent
      complex proteins cadherin and beta-catenin were localized to plasma membrane
      suggesting stabilized adherent junctions in PHB silenced cells. Our findings
      demonstrated a function of PHB in the control of a central signaling pathway
      involved in cell growth and malignant transformation.

PMID- 16294015
TI  - Corticosteroid-induced chemotherapy resistance in urological cancers.
AB  - PURPOSE: Glucocorticoids such as dexamethasone are widely used for medication of
      urological diseases, e.g., as cotreatment of advanced prostate cancer, to improve
      appetite, weight loss, fatigue, relieve bone pain, diminish ureteric obstruction,
      to reduce the production of adrenal androgens, as an antiemetic in patients
      undergoing chemo- and/or radiotherapy together with serving as "standard" therapy
      arm in randomized studies. While the potent pro-apoptotic properties and the
      supportive effects of glucocorticoids to tumor therapy in lymphoid cells are well
      studied, the impact to growth of prostate and other urological carcinomas is
      unknown. METHODS: We isolated cells from surgical resections of 21 prostate
      tumors and measured apoptosis and viability in these primary cells and 17
      established cell lines from human prostate, bladder, renal cell and testicular
      carcinomas. RESULTS: We found that dexamethasone induces resistance regarding
      exposure to several cytotoxic agents such as taxol, gemcitabine, cisplatin, 5-FU
      and gamma-irradiation in 86% of the freshly isolated prostate tumors and in 100%
      of the established urological cell lines. No difference in dexamethasone-mediated
      protection was found in normal, benign and malignant prostate tumors.
      CONCLUSIONS: These data show for the first time that dexamethasone induced
      therapy resistance in urological carcinomas is not the exception but a more
      common phenomenon and implicate that glucocorticoids may have two faces in cancer
      therapy, a beneficial and a dangerous one.

PMID- 16294016
TI  - Cancer gene discovery using the Sleeping Beauty transposon.
AB  - Epidemiological and molecular data support the hypothesis that cancer results
      from a series of acquired somatic mutations. Discovering the initial mutations
      required for oncogenesis has long been a goal of cancer research. To date, the
      majority of causative mutations have been identified based on their ability to
      act in a dominant fashion and/or because they are activated by chromosomal
      translocations. Forward genetic screens are necessary for unbiased discovery of
      the remaining unknown oncogenic mutations. Two recent projects have demonstrated
      the feasibility of using the Sleeping Beauty transposon as an insertional mutagen
      for cancer gene discovery. In this article we discuss the history of cancer gene
      discovery and propose novel forward genetic screens using Sleeping Beauty
      transposon aimed at specific tissues and accelerating the discovery of recessive
      tumor suppressor genes.

PMID- 16294017
TI  - Loading and unloading: orchestrating centrosome duplication and spindle assembly
      by Ran/Crm1.
AB  - The cell cycle is an intricate process of DNA replication and cell division that
      concludes with the formation of two genetically equivalent daughter cells. In
      this progression, the centrosome is duplicated once and only once during the G1/S
      transition to produce the bipolar spindle and ensure proper chromosome
      segregation. The presence of multiple centrosomes in cancer cells suggests that
      this process is mis-regulated during carcinogenesis. This suggests that certain
      factors exist that license the progression of centrosome duplication and serve to
      inhibit further duplications during a single cell cycle. Recent studies suggest
      that the Ran/Crm1 complex not only regulates nucleocytoplasmic transport but is
      also independently involved in mitotic spindle assembly. Factors that are capable
      of interacting with Ran/Crm1 through their nuclear export sequences, such as
      cyclins/cdks, p53 and Brca1/2, may potentially function as centrosome checkpoints
      akin to the G1/S and G2/M checkpoints of the cell cycle. Our recent findings
      indicate that nucleophosmin, a protein whose trafficking is mediated by the
      Ran/Crm1 network, is one of such checkpoint factors for maintaining proper
      centrosome duplication. We propose that Ran/Crm1 may act as a 'loading dock' to
      coordinate various checkpoint factors in regulating the fidelity of centrosome
      duplication during cell cycle progression, and the disruption of these processes
      may lead to genomic instability and an acceleration of oncogenesis.

PMID- 16294018
TI  - Identification of genes downregulated in tumor cells expressing antisense
      glutaminase mRNA by differential display.
AB  - Ehrlich ascites tumor cells (EATC) is a highly proliferative malignant cell line
      derived from mouse mammary epithelia, whereas their derivative, 0.28AS-2 cells,
      expressing antisense glutaminase mRNA, show a less transformed phenotype and loss
      of their tumorigenic capacity in vivo correlated with an inhibition of
      glutaminase expression. The mRNA differential display technique was applied to
      these two cell lines for the identification and isolation of genes whose
      transcription was altered. Side-by-side comparisons of cDNA patterns among
      relevant RNA samples revealed four genes significantly downregulated in 0.28AS-2
      cells: high-mobility group Hmga2 protein, Fmnl3 or formin-like protein 3, Nedd-4
      ubiquitin-protein ligase, and ubiquitin carboxyl-terminal hydrolase Usp-15. These
      positives were confirmed by Northern analysis. The four targeted genes have
      relevant functions in cell growth and proliferation. Our results show the
      validity of mRNA differential display technique to get insights into the
      molecular mechanisms underlying the acquisition of a more differentiated
      phenotype by tumor cells after inhibition of glutaminase expression.

PMID- 16294019
TI  - Caveolin-1-deficient mice have an increased mammary stem cell population with
      upregulation of Wnt/beta-catenin signaling.
AB  - Here, we show that a caveolin-1 (Cav-1) deficiency leads to an amplification of
      the adult mammary stem cell population, both in vivo and in vitro. First, the
      expression of two stem cell markers, Sca-1 and Keratin 6, is dramatically
      increased in the hyperplastic mammary ducts of Cav-1 deficient mice, suggesting
      that loss of Cav-1 induces the accumulation of a progenitor cell population in
      the mammary gland. To independently validate these results, we reconstituted
      mammary acini formation in vitro via a 3D Matrigel assay system--using primary
      cultures of mammary epithelial cells derived from WT and Cav-1 deficient mice. We
      show that Cav-1 null 3D epithelial structures display an intense increase in the
      expression of three stem cell markers, i.e., Sca-1, keratin 6 and keratin 5.
      Overall, we observed a 2-to-3 fold increase in the number of Cav-1 KO acini that
      are positive for a given stem cell marker. Also, we show that such amplification
      of progenitor cells has functional consequences, as demonstrated by the abnormal
      presence of myoepithelial cells in the hyperplastic lesions of Cav-1 deficient
      mammary glands. Finally, we provide evidence that hyper-activation of Wnt/beta
      catenin signaling may constitute one of the down-stream mechanisms leading to
      mammary stem cell accumulation. The longevity and slow-dividing properties of
      mammary stem cells facilitates the accumulation of genetic alterations, and
      renders these progenitor cells the likely precursors of malignant derivatives. As
      such, we propose that loss of Cav-1 induces the accumulation of mammary stem
      cells, and that this event may be an initiating factor during mammary
      tumorigenesis.

PMID- 16294020
TI  - Combining EGFR targeted therapy with chemotherapy in pancreatic cancer: is timing
      important?

PMID- 16294021
TI  - Structural basis for gene activation by p53 family members.
AB  - The p53 tumor suppressor is a modular transcription factor that determines
      cellular outcome (cell cycle arrest and DNA repair vs. apoptosis) in response to
      stress signals. The two p53 homologues, p63 and p73 play an important role in
      development but also act as tumor suppressors. The p53 family members are highly
      homologous in the activation domain (AD), the DNA-binding domain (DBD) and the
      tetramerization domain (TD) but differ in the C-terminus. Indeed, the p53 C
      terminus contains a basic domain (BD) whereas p63/p73 have a sterile alpha motif
      (SAM) domain and an inhibitory domain (ID). In addition to the full-length
      proteins, the p53 family genes produce multiple isoforms truncated at the NH2-
      and/or C-terminus. Importantly, every functional domain is a determinant in the
      transactivation of specific target genes by the p53 family members. Distinct post
      translational modifications and interactions with cofactors further modulate the
      transcriptional activity of the p53 family members in response to particular
      stress signals. Therefore, divergence in the composition of the p53 family
      proteins is responsible for the diversity of p53 family functions.

PMID- 16294022
TI  - Expression and functional analysis of platelet-derived growth factor in uterine
      leiomyomata.
AB  - OBJECTIVE: To examine the expression of PDGF and its receptors in leiomyoma
      tissue and to investigate the regulation of PDGF on leiomyoma cell proliferation.
      MATERIALS AND METHODS: The expression of PDGF and its receptors was examined in
      21 pairs of uterine leiomyoma and the adjacent myometrium tissues using an
      immunostaining method. Paired cultures of leiomyoma and normal myometrium cells
      were established and treated with PDGF. Total RNA was extracted from leiomyoma
      and myometrial cells for detection of the expression of proliferating cell
      nuclear antigen (PCNA) and collagen alpha1 (I, III) by semi-quantitative PCR.
      RESULT: The expression of PDGF-AA and PDGF-BB in leiomyoma tissue is obviously
      higher than that in the matched myometrial tissue (P < 0.05). In addition, the
      expression of PDGF-BB in secretory phase is higher than that in proliferative
      phase of the menstrual cycle (P = 0.027) in leiomyoma tissue. The expression of
      PCNA and collagen alpha1 (I) were increased in both leiomyoma and myometrial
      cells after treatment of PDGF, whereas the expression levels were greater in
      leiomyoma cells than that in myometrial cells. CONCLUSION: The expression of PDGF
      and its receptors in leiomyoma and myometrial tissue varied during the menstrual
      cycle. PDGF may play a role in the pathogenesis of leiomyomas through a mechanism
      involved in not only the proliferation of leiomyoma cells but also excessive
      expression of extra cellular molecules.

PMID- 16294023
TI  - RNA interference targeting of A1 receptor-overexpressing breast carcinoma cells
      leads to diminished rates of cell proliferation and induction of apoptosis.
AB  - To determine if A1 adenosine receptors mediate breast tumorigenesis, we evaluated
      A1 receptor expression in human tumor cell lines and human primary breast tumor
      tissues using both quantitative RT-PCR and Western blot analysis. A1 receptor
      mRNA expression is upregulated in all breast tumor cell lines examined (n=7)
      compared to normal mammary epithelial cells/cell lines (n=3) as determined by
      quantitative RT-PCR analysis. Western blot analysis indicates that protein
      expression of A1 adenosine receptor is higher in 15 (62.5%) of 24 human primary
      breast tumor tissues than in matched normal breast tissue. To explore its
      cellular function, the A1 adenosine receptor was depleted by small interfering
      RNA (siRNA) in MDA-MB-468 human breast tumor cells. Depletion of A1 receptors in
      MDA-MB-468 breast tumor cells attenuated both cell growth and cell proliferation
      as measured by cell number counts and [(14)C]-thymidine incorporation,
      respectively. Cell cycle analysis indicated that depletion of A1 receptors by
      siRNA impairs G(1) checkpoint, leading to marked accumulation of cells in G(2)/M
      phase, in agreement with the inhibitory effect on cell proliferation. Further
      supporting this finding, synchronization studies of Hela cells in various cell
      cycle phases suggest that A1 receptor expression is suppressed in G(2)/M cells
      and depletion of A1 receptor expression by siRNA produced differential expression
      of several key cell cycle regulators, i.e., accumulation of the cyclin-dependent
      kinase inhibitor p27 with concomitant reduction of CDK4 and cyclin E proteins. In
      addition to the impact on cell cycle progression, depletion of A1 receptors by
      siRNA results in substantial cell death and apoptosis as determined by FACS
      analysis and annexin V staining method. Together these findings suggest that the
      A1 adenosine receptor may contribute to tumor cell growth and survival in breast
      tumor cells.

PMID- 16294024
TI  - Blimp1 and the emergence of the germ line during development in the mouse.
AB  - To elucidate the mechanism for the specification of primordial germ cells (PGCs)
      in mice, we have developed and exploited the methods of single cell analysis.
      Based on these studies, we proposed a molecular program associated with this
      process, a key event of which is the repression of homeobox genes that are,
      without exception, upregulated in somatic neighbors. We have now identified
      Blimp1, a potent transcriptional repressor of a histone methyltransferase
      subfamily, as a key regulator of PGC specification. Indeed, the unexpected early
      onset of Blimp1 expression in a few cells at the most proximal-posterior epiblast
      cells marks the origin of the germ cell lineage. Disruption of Blimp1 function
      resulted in aberrant PGC-like cells with a deregulated intrinsic gene expression
      program at a very early stage, which demonstrates that Blimp1 is a critical
      determinant of the germ line in mice.

PMID- 16294025
TI  - Modulation of TRAIL-induced tumor cell apoptosis in a hypoxic environment.
AB  - Hypoxia induces Hif-1alpha and selects for loss of wild-type p53 function, both
      of which can promote tumor cell survival. We evaluated the ability of TRAIL to
      induce apoptosis of human tumor cell lines exposed to hypoxia. H460 lung cancer
      cells express low levels of Hif-1alpha, stabilize wild-type p53 during hypoxia,
      and undergo TRAIL-induced apoptosis. In U2OS osteosarcoma or PA1 ovarian
      teratocarcinoma cells, high levels of Hif-1alpha and low levels of stable p53 are
      detected during hypoxia, and cells undergo low levels of TRAIL-induced apoptosis
      as compared to H460 cells. H460 cells are sensitized to TRAIL-induced apoptosis,
      whereas U2OS are protected, and little apoptosis is observed in relatively TRAIL
      resistant PA1 during hypoxia. Forced expression of Hif-1alpha is also
      surprisingly a potent inducer of apoptosis in wild-type p53 expressing H460 cells
      and further promotes TRAIL-induced apoptosis. TRAIL-sensitive wild-type p53
      expressing HCT116 colon carcinoma cells modestly elevate Hif-1alpha levels and
      are equally or slightly more sensitive to TRAIL during hypoxia. In contrast, p53
      null HCT116 have higher levels of Hif-1alpha during normoxia and are extremely
      sensitive to TRAIL, but are protected from TRAIL-induced apoptosis during
      hypoxia. We hypothesize that a hypoxic tumor microenvironment may alter
      sensitivity to TRAIL, which may be impacted by Hif-1alpha levels and p53 status.
      These findings suggest that particular attention to hypoxic regions of tumors and
      sensitizers to hypoxia-induced cell death may be required to optimize therapeutic
      combinations using TRAIL.

PMID- 16294026
TI  - Activating mutations in c-KIT and PDGFRalpha are exclusively found in
      gastrointestinal stromal tumors and not in other tumors overexpressing these
      imatinib mesylate target genes.
AB  - Previous studies have shown that Imatinib mesylate (Gleevec), a selective
      tyrosine kinase inhibitor of c-KIT and platelet-derived growth factor receptors
      (PDGFR), is highly effective in c-KIT/CD117-positive gastrointestinal stromal
      tumors (GIST), especially in those having activating mutations in c-kit exon 11.
      In addition, gain-of-function mutations in the juxtamembrane domain (exon 12) and
      the kinase activation loop (exon 18) of PDGFRalpha were found in GISTs.
      Importantly, the presence and type of these mutually exclusive c-KIT or
      PDGFRalpha mutations were found to be associated with the response to imatinib.
      Here, we examined the prevalence of c-kit exon 11 and PDGFRalpha exons 12 and 18
      mutations in other tumor types known to express these tyrosine kinase receptors
      in order to explore which other cancer types may potentially benefit from
      imatinib treatment. We determined the mutational status of these commonly mutated
      exons by direct sequencing in 11 different tumor types (in total: 215 unrelated
      cases), including GIST, chordoma, and various distinct tumors of lung, brain and
      its coverings, and skin cancer. Of the 579 exons examined (211 c-kit exon 11, 192
      PDGFRalpha exon 12, 142 PDGFRalpha exon18, 17 PDGFRbeta exon 12 and 17 PDGFRbeta
      exon 18), only 12 (all GIST) harbored mutations (10 c-kit exon 11 and 2
      PDGFRalpha exon18). From these data we conclude that activating c-KIT and PDGFR
      mutations are sporadic in human cancers known to overexpress these tyrosine
      kinase receptor genes and suggest that, except in GIST, this overexpression is
      not correlated with activating mutations. The latter may imply that these wild
      type c-KIT and PDGFR tumor types will probably not benefit from imatinib
      treatment.

PMID- 16294027
TI  - Use of the 13C-sucrose breath test to assess chemotherapy-induced small
      intestinal mucositis in the rat.
AB  - Mucositis is a debilitating side-effect of chemotherapy which affects the mucosa
      of the gastrointestinal tract, particularly the small intestine. Currently there
      are no simple, noninvasive methods to detect and monitor small intestinal
      function and the severity of mucosal damage. Activity of the brush-border enzyme
      sucrase provides an indicator of small intestinal absorptive function that
      remains relatively constant throughout life. Measuring 13CO2 levels in expired
      breath following ingestion of 13C-sucrose is a non-invasive marker of total
      intestinal sucrase activity. We evaluated the sucrose breath test (SBT) as an
      indicator of small intestinal injury and dysfunction, utilizing a rat model of
      chemotherapy-induced mucositis. SBT results reflected the time-course of damage
      and repair after methotrexate (MTX) treatment, with damage most severe 72 h after
      chemotherapy, and repair commencing after 96 h. SBT results correlated
      significantly with jejunal sucrase activity determined biochemically (r2= 0.89; p
      < 0.005). Moreover, calcium folinate ingested prior to chemotherapy totally
      prevented damage to the small intestinal mucosa induced by MTX, as assessed by
      the SBT in concert with structural, and biochemical indices. The SBT provides a
      simple, non-invasive, integrated measure of small intestinal damage and function.
      The SBT holds significant potential to monitor small intestinal function in
      cancer patients undergoing chemotherapy. This technique possesses further
      applicability to the screening of newly-developed agents for potential
      gastrointestinal toxicity including the development of new therapies targeted at
      minimising or preventing the onset of chemotherapy-induced mucositis.

PMID- 16294028
TI  - Cross talk between mitochondria and superoxide generating NADPH oxidase in breast
      and ovarian tumors.
AB  - Reactive oxygen species (ROS) signal cascades involved in cell growth, cell
      death, mitogenesis, angiogenesis and carcinogenesis. ROS are produced as a
      byproduct of oxidative phosphorylation (OXPHOS) in the mitochondria. It is
      estimated that 2-4% of the oxygen consumed during OXPHOS is converted to ROS.
      Besides mitochondria, NADPH-oxidase 1 (Nox1) also generates a significant amount
      of ROS in the cell. In this paper, we tested the hypothesis that mitochondria
      control Nox 1 redox signaling and the loss of control of this signaling
      contributes to tumorigenesis. We analyzed Nox1 expression in a mitochondrial gene
      knockout (rho(0)) cell line and in the isogenic cybrid cell line in which
      mitochondrial genes were restored by transfer of wild type mitochondria into
      rho(0) cells. Our study revealed, for the first time, that the inactivation of
      mitochondrial genes leads to down-regulation of Nox1 and that the transfer of
      wild type mitochondrial genes restored the Nox1 expression to a level comparable
      to that in the parental cell line. Consistent with Nox1 down-regulation, we found
      that rho(0) cells contained low levels of superoxide anion and that superoxide
      levels reversed to parental levels in cybrid cells when Nox1 expression was
      restored by transfer of wild type mitochondria. Increasing mitochondrial
      superoxide levels also increased the expression of Nox1 in parental cells.
      Confocal microscopy studies revealed that Nox1 localizes in the mitochondria.
      Nox1 was highly expressed in breast (86%) and ovarian (71%) tumors and that its
      expression positively correlated with expression of cytochrome C oxidase encoded
      by mtDNA. Our study, described in this paper demonstrates the existence of cross
      talk between the mitochondria and NADPH oxidase. Furthermore, our studies suggest
      that mitochondria control Nox1 redox signaling and the loss of control of this
      signaling contributes to breast and ovarian tumorigenesis.

PMID- 16294029
TI  - Subcellular localization of the cyclin dependent kinase inhibitor Sic1 is
      modulated by the carbon source in budding yeast.
AB  - The cyclin dependent kinase inhibitor Sic1 and the cyclin Clb5 are essential
      regulators of the cyclin dependent kinase Cdc28 during the G1 to S transition in
      budding yeast. Yeast enters S phase after ubiquitin-mediated degradation of Sic1,
      an event triggered by Cln1, 2-Cdc28 mediated phosphorylation. We recently showed
      that Sic1 is involved in carbon source modulation of the critical cell size
      required to enter S phase. Here we show that the amount and sub-cellular
      localization of Sic1 are also carbon source-modulated. We identify a bipartite
      nuclear localization sequence responsible for nuclear localization of Sic1 and
      for correct cell cycle progression in a carbon-source dependent manner. Similarly
      to Cip/Kip proteins-Sic1 mammalian counterparts-Sic1 facilitates nuclear
      accumulation of its cognate cyclin, since cytoplasmic building-up of Clb5 is
      observed upon switching off expression of the SIC1 gene. Our data indicate a
      previously unrecognized inhibitor/activator dual role for Sic1 and put it among
      key molecules whose activity is regulated by their nuclear-cytoplasmic
      localization.

PMID- 16294030
TI  - Targeting hypoxia and angiogenesis through HIF-1alpha inhibition.
AB  - Hypoxia is an important phenomenon in the tumor microenvironment. Hypoxic tumors
      are more aggressive and resistant to anti-neoplastic treatments. HIF-1alpha plays
      a major role in the response of tumors to hypoxia, and it is mainly responsible
      for the "angiogenic switch". HIF-1alpha contributes to tumor aggressiveness,
      invasiveness, and resistance to radiotherapy and chemotherapy. Targeting HIF
      1alpha is an attractive strategy, with the potential for disrupting multiple
      pathways crucial for tumor growth. We review recent findings on the potential
      efficacy of small molecules to downregulate HIF-1alpha. These promising drugs
      inhibit HIF-1alpha synthesis or transcriptional activity by blocking a variety of
      steps in several different signaling pathways. Blocking HIF-1alpha activity
      should not only downregulate tumor angiogenesis, but also interfere with
      glycolytic metabolism and tumor cell growth. This strategy could also improve the
      efficiency of established tumor therapies.

PMID- 16294032
TI  - Switching on-off Snail: LOXL2 versus GSK3beta.
AB  - Epithelial-mesenchymal transition (EMT) is considered as an essential determinant
      of carcinoma progression. The transcription factor Snail controls EMT by
      repressing E-cadherin gene expression and other epithelial genes. Snail protein
      stability and cellular localization is finely controlled by GSK3beta-dependent
      phosphorylation and subsequent ubiquitination. GSK3beta phosphorylates Snail at
      two different motifs which induce its nuclear export and association with beta
      Trcp thus leading to Snail degradation. Recently, Snail was found to interact
      physical and functionally with LOXL2, a member of the lysyl oxidase gene family.
      Interestingly, LOXL2 seems to attenuate the GSK3beta-dependent Snail degradation.
      Here, we discuss the relevance of this new potential mechanism of regulation and
      the role of LOXL2 during carcinoma progression.

PMID- 16294031
TI  - Cisplatin-induced GADD34 upregulation potentiates oncolytic viral therapy in the
      treatment of malignant pleural mesothelioma.
AB  - BACKGROUND: NV1066, a replication-competent oncolytic herpes simplex virus type 1
      (HSV-1) attenuated by a deletion in the gene gamma(1)34.5, preferentially
      replicates in and kills malignant cells. gamma(1)34.5 encodes ICP34.5, a viral
      protein essential for productive replication, which has homology with mammalian
      stress response induced GADD34 (growth arrest and DNA damage-inducible protein).
      We hypothesized that cisplatin upregulates GADD34 expression, which enhances
      NV1066 replication and oncolysis. METHODS: Ten human malignant pleural
      mesothelioma (MPM) cell lines were infected with NV1066 at multiplicities of
      infection (MOI; ratio of viral particles per tumor cell) 0.005 to 0.8 in vitro,
      with and without cisplatin (1 to 4 microM). In the MPM cell line VAMT, viral
      replication was determined by plaque assay, cell kill by lactate dehydrogenase
      assay, and GADD34 induction by quantitative RT-PCR and Western blot. Synergistic
      efficacy was confirmed by the isobologram and combination index methods of Chou
      Talalay. GADD34 upregulation by cisplatin was inhibited with GADD34 siRNA to
      further confirm the synergistic efficacy dependence with GADD34. RESULTS:
      Combination therapy with NV1066 and cisplatin showed strong synergism in
      epithelioid (H-2452, H-Meso), sarcomatoid (H-2373, H-28), and biphasic (JMN, Meso
      9, MSTO-211H) MPM cell lines, and an additive effect in others. In VAMT cells
      combination therapy enhanced viral replication 4 to 11-fold (p < 0.01) and cell
      kill 2 to 3-fold (p < 0.01). Significant dose reductions for both agents (2 to
      600-fold) were achieved over a wide range of therapeutic-effect levels (LD50
      LD99) without compromising cell kill. Synergistic cytotoxicity correlated with
      GADD34 upregulation (2 to 4-fold, p < 0.01) and was eliminated following
      transfection with GADD34 siRNA. CONCLUSION: Cisplatin-induced GADD34 expression
      selectively enhanced the cytotoxicity of the gamma(1)34.5-deficient oncolytic
      virus, NV1066. This provides a cellular basis for combination therapy with
      cisplatin and NV1066 to treat MPM and achieve synergistic efficacy, while
      minimizing dosage and toxicity.

PMID- 16294033
TI  - Genotoxic and endoplasmic reticulum stresses differentially regulate TRB3
      expression.
AB  - TRB3 has recently been identified as a potential pro-apoptotic protein that may
      modulate the Akt/PKB-dependent signaling pathway. Here we report that TRB3
      expression is strongly upregulated by endoplasmic reticulum (ER) stress-inducing
      agents that (1) promote ER Ca2+ pool depletion or (2) disrupt protein
      trafficking. Genotoxic stress (DNA damage)-inducing agents, by contrast,
      downregulate TRB3 expression and appear to do so through both p53-dependent and 
      independent mechanisms. To the best of our knowledge, TRB3 is the first gene that
      is upregulated by ER stress and downregulated following genotoxic stress.
      Collectively, these findings highlight the importance of stress-specific
      signaling cascades as well as point out the seemingly divergent roles that TRB3
      may play in the cellular stress response.

PMID- 16294035
TI  - Chemotherapy regimen GOLF induces apoptosis in colon cancer cells through multi
      chaperone complex inactivation and increased Raf-1 ubiquitin-dependent
      degradation.
AB  - The multi-drug combination of oxaliplatin (OXA), 5-Fluorouracil (5-FU) and
      leucovorin (LF) is currently considered as the gold standard treatment for
      metastatic colorectal carcinoma. In previous studies, we have studied a
      chemotherapy regimen containing gemcitabine (GEM), OXA, LF, and 5-FU (named GOLF
      regimen) that has shown a good safety profile and highly significant anti-tumor
      activity. In the present study, we have investigated on the anti-tumour
      mechanisms of GOLF in human colon cancer HT-29 and WiDr cell lines. We have found
      that GOLF induced growth inhibition that was largely caused by apoptosis
      differently from other combinations. Moreover, the different drugs composing GOLF
      were highly synergistic in inducing growth inhibition. Apoptosis induced by GOLF
      combination was paralleled by PARP cleavage and caspase 9 and 3 activation that
      were not recorded in the other combinations. An about 85% decrease of the
      activity of Erk and Akt was found in GOLF-treated cells. These effects were
      likely due to decreased expression of the upstream activator Raf-1 and of Akt
      itself, respectively. The intracellular levels of these signalling components can
      be post-translationally regulated by ubiquitin-dependent degradation through
      proteasome. Therefore, we have evaluated the expression of some chaperone
      components and we have found that GOLF did not affect the expression of both heat
      shock protein (HSP) 90 and 27 but induced an about 90% increase of HSP70 levels
      suggesting the inactivation of the multi-chaperone complex. Moreover, an about 4
      fold increase of the ubiquitination of Raf-1 was also found and the addition for
      12 h of 10 microM proteasome inhibitor lactacystin caused an accumulation of the
      ubiquitinated isoforms of Raf-1. In conclusions, GOLF was a combination highly
      synergistic in inducing both growth inhibition and apoptosis of colon cancer
      cells. These effects likely occurred through the disruption of critical survival
      pathways and the inactivation of multi-chaperone complex.

PMID- 16294034
TI  - Deciphering transcriptional regulatory elements that encode specific cell cycle
      phasing by comparative genomics analysis.
AB  - Transcriptional regulation is a major tier in the periodic engine that mobilizes
      cell cycle progression. The availability of complete genome sequences of multiple
      organisms holds promise for significantly improving the specificity of
      computational identification of functional elements. Here, we applied a
      comparative genomics analysis to decipher transcriptional regulatory elements
      that control cell cycle phasing. We analyzed genome-wide promoter sequences from
      12 organisms, including worm, fly, fish, rodents and human, and identified
      conserved transcriptional modules that determine the expression of genes in
      specific cell cycle phases. We demonstrate that a canonical E2F signal encodes
      for expression highly specific to the G1/S phase, and that a cis-regulatory
      module comprising CHR-NF-Y elements dictates expression that is restricted to the
      G2 and G2/M phases. B-Myb binding site signatures occur in many of the CHR-NF-Y
      target genes, suggesting a specific role for this triplet in the regulation of
      the cell cycle transcriptional program. Remarkably, E2F signals are conserved in
      promoters of G1/S genes in all organisms from worm to human. The CHR-NF-Y module
      is conserved in promoters of G2/M regulated genes in all analyzed vertebrates.
      Our results reveal novel modules that determine specific cell cycle phasing, and
      identify their respective putative target genes with remarkably high specificity.

PMID- 16294036
TI  - New talents for an old acquaintance: the SR protein splicing factor ASF/SF2
      functions in the maintenance of genome stability.
AB  - ASF/SF2 is a well-studied SR protein that plays important roles in premRNA
      splicing and other aspects of RNA metabolism. Genetic inactivation experiments
      have revealed the fundamental roles of ASF/SF2 and other SR proteins in cell
      viability and animal development. However, the nature of the events triggered by
      in vivo depletion of ASF/SF2 remained largely elusive. Recently, we have
      demonstrated a significant function of ASF/SF2 in the maintenance of genome
      stability by preventing the formation of R loops, which provided new insights
      into the essential roles of ASF/SF2 in cellular physiology.

PMID- 16294037
TI  - Loss of caveolin-1 causes the hyper-proliferation of intestinal crypt stem cells,
      with increased sensitivity to whole body gamma-radiation.
AB  - Caveolin-1 (Cav-1) is a protein marker for caveolae organelles, and acts as a
      scaffolding protein to negatively regulate the activity of signaling molecules by
      binding to and releasing them in a timely fashion. We have previously shown that
      loss of Cav-1 promotes the proliferation of mouse embryo fibroblasts (MEFs) in
      vitro. Here, to investigate the in vivo relevance of these findings, we evaluated
      the turnover rates of small intestine crypt stem cells from WT and Cav-1
      deficient mice. Interestingly, we show that Cav-1 null crypt stem cells display
      higher proliferation rates, as judged by BrdU and PCNA staining. In addition, we
      show that Wnt/beta-catenin signaling, which normally controls intestinal stem
      cell self-renewal, is up-regulated in Cav-1 deficient crypt stem cells. Because
      the small intestine constitutes one of the main targets of radiation, we next
      evaluated the role of Cav-1 in radiation-induced damage. Interestingly, after
      exposure to 15 Gy of gamma-radiation, Cav-1 deficient mice displayed a decreased
      survival rate, as compared to WT mice. Our results show that after radiation
      treatment, Cav-1 null crypt stem cells of the small intestine exhibit far more
      apoptosis and accelerated proliferation, leading to a faster depletion of crypts
      and villi. As a consequence, six days after radiation treatment, Cav-1(-/-) mice
      lost all their crypt and villus structures, while WT mice still showed some
      crypts and intact villi. In summary, we show that ablation of Cav-1 gene
      expression induces an abnormal amplification of crypt stem cells, resulting in
      increased susceptibility to gamma-radiation. Thus, our studies provide the first
      evidence that Cav-1 normally regulates the proliferation of intestinal stem cells
      in vivo.

PMID- 16294038
TI  - In situ detection of specific DNA double strand breaks using rolling circle
      amplification.
AB  - We have developed a method to localize DNA double strand breaks (DSBs) in situ in
      cultured mammalian cells. Adenoviruses encoding Saccharomyces cerevisiae HO
      endonuclease and its cleavage site were used to induce site-specific DSBs.
      Rolling circle amplification (RCA), a sensitive method that allows the detection
      of single molecular event by rapid isothermal amplification, was used to localize
      the broken ends in situ. Punctate RCA signals were only seen in the cells that
      had been infected with both adenoviruses encoding HO endonuclease and HO cleavage
      site, but not in the cells mock-infected or infected with the site or
      endonuclease virus only. With use of a chemical crosslinker, in situ RCA and
      immunofluorescence (IF) can be performed simultaneously on the same sample. This
      methodology provides a novel approach for investigation of DNA recombination, DNA
      repair, and checkpoint controls in mammalian cells.

PMID- 16294039
TI  - AML1-ETO needs a partner: new insights into the pathogenesis of t(8;21) leukemia.
AB  - The detailed characterization of genetic and molecular aberrations in acute
      myeloid leukemia (AML) has substantially improved our understanding of the
      pathogenesis of this disease. With an incidence of up to 12% in all AML cases,
      the translocation t(8;21), forming the AML1-ETO fusion gene, is one of the most
      common genetic aberrations in AML. Experimental data have shown that AML1-ETO is
      not sufficient to induce leukemia by itself, but has to collaborate with other
      genetic alterations for leukemic transformation. These data are supported by
      observations in AML patients, who recurrently show activating mutations of the
      receptor tyrosine kinase FLT3 or c-KIT together with the AML1-ETO fusion gene.
      These findings might have clinical implications and provide a rationale to test
      RTK inhibitors in the treatment of patients with core binding factor AML and
      concurrent activating RTK mutations.

PMID- 16294040
TI  - Preferential occurrence of chromosome breakpoints within early replicating
      regions in neuroblastoma.
AB  - Neuroblastoma (NB) is a frequent paediatric extra cranial solid tumor
      characterized by the occurrence of unbalanced chromosome translocations,
      frequently, but not exclusively, involving chromosomes 1 and 17. We have used a 1
      Mb resolution BAC array to further refine the mapping of breakpoints in NB cell
      lines. Replication timing profiles were evaluated in 7 NB cell lines, using DNAs
      from G1 and S phases flow sorted nuclei hybridised on the same array. Strikingly,
      these replication timing profiles were highly similar between the different NB
      cell lines. Furthermore, a significant level of similarity was also observed
      between NB cell lines and lymphoblastoid cells. A segmentation analysis using the
      Adaptative Weights Smoothing procedure was performed to determine regions of
      coordinate replication. More than 50% of the breakpoints mapped to early
      replicating regions, which account for 23.7% of the total genome. The breakpoints
      frequency per 10(8) bases was therefore 10.84 for early replicating regions,
      whereas it was only 2.94 for late replicating regions, these difference being
      highly significant (p < 10(-4)). This strong association was also observed when
      chromosomes 1 and 17, the two most frequent translocation partners in NB were
      excluded from the statistical analysis. These results unambiguously establish a
      link between unbalanced translocations, whose most likely mechanism of occurrence
      relies on break-induced replication, and early replication of the genome.

PMID- 16294041
TI  - The intersection of inheritance and metastasis: the role and implications of
      germline polymorphism in tumor dissemination.
AB  - Metastasis is an enormously complex process that involves both spatial and
      temporal barriers. Metastatic cells must not only acquire all of the
      characteristics of a primary tumor, but additionally must be capable of invasion,
      survival during transit and in the secondary site, interact productively with a
      novel microenvironment and proliferate to form a clinically relevant lesion.(1)
      Adding complexity to the process is the fact that it can be years or even decades
      after diagnosis of the primary tumor before the secondary tumors are apparent. A
      number of models have been proposed to explain the origins of metastasis.
      However, while all of the models can account for some aspects of the experimental
      observations, suggesting they may be at least in part true, none adequately
      explain all of the data. This implies that the existing models are likely to be
      too simplistic and additional factors must be considered to adequately account
      for existing and newly emerging data.

PMID- 16294042
TI  - ATP-dependent chromatin-remodeling complexes in DNA double-strand break repair:
      remodeling, pairing and (re)pairing.
AB  - The genomic integrity of a eukaryotic cell is challenged by over 10,000
      chromosomal lesions per day. Therefore the cell has evolved efficient mechanisms
      to recognize, signal, and repair DNA breaks. Defects in any of these steps can
      lead to chromosomal aberrations and cancers. As these lesions must be repaired in
      the context of chromatin, both chromatin-modifying and nucleosome-remodeling
      enzymes have been implicated in DNA damage repair. We reported recently that the
      RSC and Swi/Snf ATP-dependent chromatin-remodeling complexes are involved in DSB
      repair specifically by homologous recombination. Here we discuss how such enzymes
      might be recruited to DNA breaks, why so many remodelers are recruited to sites
      of DSBs, and a possible functional connection between RSC's roles in sister
      chromatid cohesion and DSB repair.

PMID- 16294043
TI  - The senescent side of tumor suppression.
AB  - Neoplastic transformation of human cells is a rare event that requires overcoming
      anti-tumoral cellular responses. Oncogene-induced senescence (OIS) is considered
      a crucial tumor suppressor mechanism controlling unchecked proliferation driven
      by oncogenic mutation. However, the analysis of OIS has been restricted so far to
      cultured cells. Recently, we have identified novel molecular markers of OIS and
      we have demonstrated the occurrence of senescence using mouse models of oncogenic
      activation. Importantly, we have found that senescent cells are abundant in
      premalignant lesions of the skin, the lung, and the pancreas. In contrast,
      senescent cells were rare in the malignant lesions developed by these same
      animals. These observations, together with similar ones by other investigators,
      strongly argue for the occurrence of OIS in vivo and for its active role in
      restricting tumor development. These results open the possibility of using
      senescence markers as diagnostic and prognostic tools, and prompt the
      investigation on the potential therapeutical use of senescence-inducing drugs.

PMID- 16294044
TI  - Mechanistic insight into the Cdc28-related protein kinase Ime2 through analysis
      of replication protein A phosphorylation.
AB  - In budding yeast, the meiosis-specific protein kinase Ime2 is required for normal
      meiotic progression. Current evidence suggests that Ime2 is functionally related
      to Cdc28, the major cyclin-dependent kinase in yeast that is essential for both
      cell cycle and meiosis. We have previously reported that a natural target of Ime2
      activity is replication protein A (RPA), the cellular single-stranded DNA-binding
      protein that performs critical functions during DNA replication, repair and
      recombination. Ime2-dependent RPA phosphorylation first occurs early in meiosis
      and targets the middle subunit of the RPA heterotrimeric complex (Rfa2). We now
      demonstrate that Rfa2 serine 27 (S27) is required for Ime2-dependent Rfa2
      phosphorylation in vivo. S27 is also required for Rfa2 phosphorylation in vitro
      catalyzed by immunoprecipitated Ime2. In addition, Ime2 mediates in vitro
      phosphorylation of a short peptide containing Rfa2 amino acids 23 through 29,
      thereby providing evidence that S27 itself is the phosphoacceptor.
      Phosphorylation site mapping supports this conclusion, as mass spectrometry
      analysis has revealed that at least three residues within Rfa2 amino acids 2
      through 35 become phosphorylated specifically during meiosis. Although S27 is
      embedded in a motif that is recognized by several protein kinases, this sequence
      is not a typical target of cyclin-dependent kinases. Therefore, the mechanism
      underlying Ime2 substrate recognition could differ from that of Cdc28.

PMID- 16294045
TI  - The GAR motif of 53BP1 is arginine methylated by PRMT1 and is necessary for 53BP1
      DNA binding activity.
AB  - The p53-binding protein 1 (53BP1) is rapidly recruited to sites of DNA double
      strand breaks and forms characteristics nuclear foci, demonstrating its role in
      the early events of detection, signaling and repair of damaged DNA. 53BP1
      contains a glycine arginine rich (GAR) motif of unknown function within its
      kinetochore-binding domain. Herein, we show that the GAR motif of 53BP1 is
      arginine methylated by protein arginine methyltransferase 1 (PRMT1), the same
      methyltransferase that methylates MRE11. 53BP1 contains asymmetric
      dimethylarginines (aDMA) within cells, as detected with methylarginine-specific
      antibodies. Amino acid substitution of the arginines within the GAR motif of
      53BP1 abrogated binding to single and double-stranded DNA, demonstrating that the
      GAR motif is required for DNA binding activity of 53BP1. Fibroblast cells treated
      with methylase inhibitors failed to relocalize 53BP1 to sites of DNA damage and
      formed few gamma-H2AX foci, consistent with our previous data that MRE11 fails to
      relocalize to DNA damage sites in cells treated with methylase inhibitors. Our
      findings identify the GAR motif as a region required for 53BP1 DNA binding
      activity and as the site of methylation by PRMT1.

PMID- 16294046
TI  - Why therapeutic response may not prolong the life of a cancer patient: selection
      for oncogenic resistance.
AB  - Most cancers do not respond to chemotherapy. Disappointedly, even objective
      clinical responses to anticancer therapy often do not translate into improvements
      in overall survival. To explain the response-survival paradox, it has been
      pointed out that effective therapy is ineffective against cancer stem cells,
      which replenish the tumor (causing relapse). In contrast, I discuss that,
      according to this scenario, patient survival will be prolonged at least by the
      duration of remission. Furthermore, stem-cell-based relapses will be sensitive to
      the initial therapy, and in theory cancer could be controlled indefinitely. To
      explain the paradox, I discuss that effective therapy selects for resistance
      among proliferating cancer cells. Importantly, mechanisms of resistance can be
      divided into nononcogenic (e.g., drug transporters and mutation in drug-targets)
      and oncogenic (e.g., apoptosis avoidance and cell cycle dysregulation). Oncogenic
      resistance is associated with highly aggressive cancer phenotype and, therefore,
      there is no increase in overall survival. I further suggest that (a) therapeutic
      response is a prerequisite for successful therapy, (b) resistance can be
      exploited for therapeutic advantage, (c) each response can be translated into
      increased survival, and (e) in slow growing tumors, cancer can be stopped without
      tumor shrinkage. Therapy will control cancer if it can selectively suppress
      proliferating cancer cells and will improve survival as long as acquired
      resistance can be exploited.

PMID- 16294047
TI  - 53BP1 oligomerization is independent of its methylation by PRMT1.
AB  - p53 binding protein 1 (53BP1) participates in the repair of DNA double stranded
      breaks (DSBs) where it is recruited to or near sites of DNA damage. Although
      little is known about the biochemical functions of 53BP1, the protein possesses
      several motifs that are likely important for its role as a DNA damage response
      element. This includes two BRCA1 C-terminal repeats, tandem Tudor domains, and a
      variety of phosphorylation sites. Here we show that a glycine-arginine rich (GAR)
      stretch of 53BP1 lying upstream of the Tudor motifs is methylated. We demonstrate
      that arginine residues within this region are important for asymmetric
      methylation by the PRMT1 methyltransferase. We further show that sequences
      upstream of the Tudor domains that do not include the GAR stretch are sufficient
      for 53BP1 oligomerization in vivo. Thus, although Tudor domains bind methylated
      proteins, 53BP1 homo-oligomerization occurs independently of Tudor function.
      Lastly, we find that deficiencies in 53BP1 generate a "hyper-rec" phenotype.
      Collectively, these data provide new insight into 53BP1, an important component
      in maintaining genomic stability.

PMID- 16294048
TI  - Are we abandoning nursing as a discipline?

PMID- 16294050
TI  - Virginia Henderson International Nursing Library: a new interface to better
      support nursing practice.

PMID- 16294051
TI  - National Association of Clinical Nurse Specialists position statement on advanced
      pharmacology: practice, curricular, and regulatory recommendations.

PMID- 16294052
TI  - Resources for critically appraising qualitative research evidence for nursing
      practice clinical question.

PMID- 16294053
TI  - Ethnic pharmacology: science, research, race, and market share.

PMID- 16294054
TI  - Strengthening clinical nurse specialist role socialization.

PMID- 16294055
TI  - Clinical coaching: a strategy for enhancing evidence-based nursing practice.
AB  - PURPOSE: The purpose of this article is to describe how clinical nurse
      specialists can promote the development of knowledge and skills in nurses as one
      step toward making evidence-based nursing practice the norm in all patient care
      settings. BACKGROUND: The need for the use of evidence in nursing practice has
      been highlighted for several decades. Moving evidence more quickly into practice
      requires that nursing use many strategies. DESCRIPTION OF STRATEGY: The strategy
      of clinical coaching is proposed in this article for the development of skills in
      nurses specifically to promote evidence-based nursing practice. Clinical coaching
      is a relationship for the purpose of building skills. This strategy is aimed at
      increasing foundational staff nurse knowledge and skills. CONCLUSION: The
      achievement and maintenance of evidence-based nursing practice take continuous
      attention from clinical nurse specialists. Clinical coaching is only one part of
      a comprehensive approach for establishing and sustaining evidence-based nursing
      practice.

PMID- 16294057
TI  - Spheres of clinical nurse specialist practice influence evidence-based care for
      patients with atrial fibrillation.
AB  - PURPOSE: The purpose of this article is to review atrial fibrillation (AF) and
      its consequences, to present sources of published evidence-based guidelines for
      management of AF, and to highlight multifaceted clinical nurse specialist (CNS)
      interventions that promote positive outcomes for patients with AF. RATIONALE: The
      number of people with AF is expected to increase from 2.3 million to more than 5
      million in the next 50 years. AF is associated with increased mortality,
      morbidity, healthcare expenditures, and decreased quality of life. Recognition of
      the growing number of AF cases and adverse consequences of AF led to development
      of evidence-based guidelines for AF management. Although nurses in diverse
      settings are accountable for providing evidence-based care for patients with AF,
      the guidelines have not been widely disseminated to nurses. DESCRIPTION: This
      discussion includes a review of the adverse consequences of AF and a summary of
      management of recently detected AF with a focus on recommendations for nursing
      activities/interventions that are supported by evidence-based guidelines.
      Multifaceted strategies directed toward nurses and nursing practice,
      patients/clients, and organizations/systems that are linked to published CNS
      competencies and outcomes are highlighted. OUTCOMES: CNS influence in all 3
      spheres of CNS practice promotes positive outcomes that include improved
      patient/client functioning and self-management, reduced complications of
      treatment, decreased fragmentation of care, advancement of professional nursing
      practice, adherence to regulatory standards, and development of patient care
      processes that are supported by published guidelines. CONCLUSIONS: With the use
      of the strategies discussed, clinical nurse specialists, whose spheres of
      influence include nursing and nursing practice, patients/clients, and
      organizations/systems, promote improved patient outcomes through implementation
      of evidence-based guidelines for AF management.

PMID- 16294056
TI  - The first diabetes educator is the family: using illness representation to
      recognize a multigenerational legacy of diabetes.
AB  - PURPOSE: This article proposes a framework for understanding multigenerational
      legacies of diabetes, which will assist with designing educational interventions
      for individuals with a known family history of type 2 diabetes.
      BACKGROUND/RATIONALE: Diabetes is a chronic illness that has an associated
      hereditary predisposition. Family members at risk in subsequent generations may
      be influenced by the prior generation's experiences. Multigenerational legacies
      and stories shape a family's health beliefs and response to illness and transmit
      patterns of adaptation across generations. METHOD: A review of the literature
      from 1984 to 2004 was conducted to identify evidence of legacies of chronic
      illness. OUTCOME: Family-systems-illness-disability Model and Theory of Illness
      Representation were used to guide the development of a framework of
      multigenerational legacies of diabetes. INTERPRETATION/CONCLUSION: A framework
      for understanding the influence of illness representation on multigenerational
      legacy of type 2 diabetes is presented. IMPLICATIONS FOR NURSING PRACTICE:
      Clinicians are in need of a useful framework that can provide direction as they
      attempt to understand the effect of a family history of diabetes on the health
      behavior of the next generation of family members with diabetes. This framework
      could serve to guide them as they probe for information relevant to the influence
      of recollections about the family member's experience with diabetes on an
      individual's health behavior.

PMID- 16294059
TI  - Nurse specialist profile: an interview with Karen Ann Doran.

PMID- 16294063
TI  - Role of hypertonic saline and pentoxifylline on neutrophil activation and tumor
      necrosis factor-alpha synthesis: a novel resuscitation strategy.
AB  - BACKGROUND: Hypertonic saline (HS) and pentoxifylline (PTX) have been shown to
      modulate polymorphonuclear neutrophil (PMN) functions after shock and sepsis. We
      hypothesized that a combination of HS and PTX (HSPTX) would down-regulate PMN
      functions and inflammatory mediator synthesis more effectively than each alone,
      possibly by acting at different steps of the signaling pathways, ultimately
      leading to an enhanced effect. METHODS: Whole blood from healthy volunteers was
      stimulated with lipopolysaccharide (LPS) (100 microg/mL), f-methionyl-leucyl
      phenylalanine (1 micromol/L), and phorbol 12-myristate 13-acetate (1 microg/mL).
      Baseline oxidative burst was measured by flow cytometry. Two different
      concentrations of NaCl to achieve increases of 10 mmol/L (HS10) and 40 mmol/L
      (HS40) above isotonicity, simulating increases in sodium levels seen after
      infusion of 3% HS and 7.5% HS, were used. PTX (2 mmol/L), HS10, HS40, HSPTX10,
      and HSPTX40 were added to whole blood concomitantly to the activators. PMN CD14
      and CD11b expression were measured by flow cytometry and tumor necrosis factor
      alpha levels by enzyme-linked immunosorbent assay in LPS-stimulated whole blood.
      RESULTS: The combination of PTX with HS10 and with HS40 markedly decreased LPS-
      (27 +/- 7 and 23 +/- 6 vs. 100; p < 0.01), f-methionyl-leucyl-phenylalanine- (54
      +/- 11 and 55 +/- 8 vs. 100; p < 0.05), and phorbol 12-myristate 13-acetate- (30
      +/- 4 and 54 +/- 9 vs. 100; p < 0.01 and p < 0.05, respectively) induced PMN
      oxidative burst. Furthermore, a significant decrease in LPS-induced neutrophil
      CD11b expression after PTX treatment (79 +/- 5 vs. 100; p < 0.05) and HSPTX40 (68
      +/- 7 vs. 100; p < 0.05) was observed. HSPTX10 (7 +/- 0.6; p < 0.001) or HSPTX40
      (6 +/- 1.4; p < 0.001) markedly decreased tumor necrosis factor-alpha production
      to levels similar to those observed with PTX alone (6.5 +/- 0.5; p < 0.001) and
      significantly lower than HS10 (110 +/- 4.9; p < 0.001) and HS40 alone (83 +/-
      1.5; p < 0.001) CONCLUSION: HSPTX down-regulates neutrophil activation and
      proinflammatory mediator synthesis more effectively that HS alone. HSPTX may have
      significant applications as a novel fluid resuscitation strategy in hemorrhagic
      shock.

PMID- 16294065
TI  - Prolonged low-volume resuscitation with HBOC-201 in a large-animal survival model
      of controlled hemorrhage.
AB  - BACKGROUND: Military guidelines call for two 500-mL boluses of Hextend for
      resuscitation in far-forward environments. This study compared a hemoglobin-based
      oxygen carrier (HBOC-201; Hemopure) to Hextend when used to treat hemorrhagic
      shock in situations of delayed definitive care military operations. METHODS:
      Yorkshire swine (55-65 kg) were hemorrhaged to a mean arterial blood pressure
      (MAP) of 30 mmHg. Hypotension was maintained for 45 minutes followed by
      resuscitation with either Hextend (HEX) (n = 8) or HBOC-201 (HBOC) (n = 8). Over
      8 hours, animals received up to 1,000 mL of either fluid in an effort to sustain
      an MAP of 60 mmHg. At the end of 8 hours, HEX animals received 2 L of lactated
      Ringer's solution followed by shed blood. HBOC animals received 4 L of lactated
      Ringer's solution only. Animals were killed and necropsied on postprocedure day
      5. Hemodynamic data were collected during shock and resuscitation. Complete blood
      counts, amylase, lactate, coagulation studies, and renal and liver function were
      measured throughout the experiment. RESULTS: Equivalent volumes were hemorrhaged
      from each group (HBOC, 44.3 +/- 2.2 mL/kg; HEX, 47.4 +/- 3.0 mL/kg). The HBOC
      group achieved the goal MAP (HBOC, 60.0 +/- 2.3 mmHg; HEX, 46.4 +/- 2.3 mmHg; p <
      0.01) and required less volume during the initial 8 hours (HBOC, 12.4 +/- 1.4
      mL/kg; HEX, 17.3 +/- 0.3 mL/kg; p < 0.01). The HBOC group had lower SvO2 (HBOC,
      46.3 +/- 2.4%; HEX, 50.7 +/- 2.5%; p = 0.12) and cardiac output (HBOC, 5.8 +/-
      0.4 L/min; HEX, 7.2 +/- 0.6 L/min; p = 0.05), but higher systemic vascular
      resistance (HBOC, 821.4 +/- 110.7 dynes . s . cm-5; HEX, 489.6 +/- 40.6 dynes . s
      . cm-5; p = 0.01). Base excess, pH, lactate, and urine output did not differ
      between groups. HEX group survival was 50% (four of eight) versus 88% for the
      HBOC group (seven of eight). All animals survived the initial 8 hours. Animals
      surviving 5 days displayed no clinical or laboratory evidence of organ
      dysfunction in either group. CONCLUSION: HBOC-201 more effectively restored and
      maintained perfusion pressures with lower volumes, and allowed for improved
      survival. These data suggest that hemoglobin-based oxygen carriers are superior
      to the current standard of care for resuscitation in far-forward military
      operations.

PMID- 16294064
TI  - Small volume resuscitation with hypertonic saline is more effective in
      ameliorating trauma-hemorrhagic shock-induced lung injury, neutrophil activation
      and red blood cell dysfunction than pancreatitic protease inhibition.
AB  - BACKGROUND: Recognition of the limitations of standard crystalloid resuscitation
      has led to the search for alternative resuscitation strategies that might better
      limit the development of trauma-hemorrhage-induced organ dysfunction and systemic
      inflammation. Thus, the goal of this study was to compare the effects of two
      resuscitation strategies alone, and in combination, with those of standard
      resuscitation with Ringers lactate (RL). The two strategies were small volume
      resuscitation with hypertonic saline (HTS) and intraluminal inhibition of
      pancreatic proteases with the serine protease inhibitor nafamostat. METHODS: Male
      rats were subjected to trauma-hemorrhagic shock (T/HS) or trauma sham-shock
      (T/SS) and resuscitated with RL, HTS, nafamostat, or the combination of HTS and
      nafamostat. The T/HS model consisted of a laparotomy plus 90 minutes of shock
      (MAP 30 mm Hg). Three hours after the end of the shock or sham-shock period, lung
      permeability, pulmonary neutrophil sequestration, neutrophil activation, red
      blood cell deformability, and gut injury were assessed. RESULTS: Both HTS and
      nafamostat reduced T/HS-induced pulmonary permeability and neutrophil
      sequestration, as well as neutrophil activation as compared with resuscitation
      with RL. However, HTS was more effective than nafamostat in reducing T/HS-induced
      acute lung injury and neutrophil activation. Additionally, HTS, but not
      nafamostat, reduced T/HS-induced RBC rigidification. Lastly, gut injury after
      T/HS was reduced to the greatest extent by the combination of HTS plus
      nafamostat. CONCLUSION: Small volume resuscitation with HTS is more effective
      than RL and nafamostat in limiting T/HS-induced acute lung injury, neutrophil
      activation and red blood cell injury.

PMID- 16294066
TI  - Endothelial dysfunction after lactated Ringer's solution resuscitation for
      hemorrhagic shock.
AB  - BACKGROUND: Endothelial dysfunction is presumed to occur after hemorrhagic shock
      and resuscitation. This study uses a novel large-animal model to evaluate the
      effects of diverse resuscitation regimens on endothelial function. METHODS:
      Twenty-seven adult domestic pigs (Sus scrofa) were used in this study. Control
      pigs (n = 3) underwent instrumentation alone. The remaining pigs experienced
      controlled hemorrhagic shock to a mean arterial blood pressure of 30 +/- 5 mm Hg
      for 45 minutes. Pigs were resuscitated to their baseline mean arterial blood
      pressure +/-5 mm Hg with either shed blood (SB; n = 8), lactated Ringers solution
      (40 mL/kg) followed by shed blood (LRSB; n = 8), or lactated Ringers solution
      alone (LR; n = 8). At baseline, 1 and 4 hours after resuscitation, acetylcholine
      (5, 10, and 15 microg/min) was infused into the proximal iliac artery to measure
      endothelial dependent relaxation (EDR). Sodium nitroprusside was infused to
      determine endothelial independent relaxation at the end of the study to insure
      smooth muscle vasomotor integrity. External iliac artery luminal diameter was
      measured using motion-mode ultrasonography. Statistical analysis was performed
      using repeated-measures analysis of variance with Tukey's post-hoc analysis.
      RESULTS: All pigs survived the experiment. Pigs required ninefold more
      resuscitation with LR (370.58 +/- 29 mL/kg) versus SB (41.45 +/- 3.5 mL/kg) or
      LRSB (76.4 +/- 1.1 mL/kg) (p < 0.05). EDR for LR pigs 1 hour after initiation of
      resuscitation (R1) was 70.4 +/- 14.4% compared with 94.2 +/- 13.4% for SB and
      106.1 +/- 8.2% for LRSB (p < 0.05). At 4 hours after resuscitation (R4), systolic
      luminal diameters were larger in the SB (0.45 +/- 0.01 cm) and LRSB (0.51 +/-
      0.02 cm) groups compared with LR (0.41 +/- 0.03 cm) (LRSB versus LR; p = 0.01).
      At R4, EDR for the LR group was 78.3 +/- 10.7% compared with SB (101.4 +/- 8.3%)
      and LRSB (106.4 +/- 7.4%) (p < 0.05). Infusion of sodium nitroprusside confirmed
      integrity of smooth muscle vasorelaxation. Analysis of serum nitric oxide levels
      revealed decreased values after resuscitation with LR (9.44 +/- 0.76 mol/L)
      compared with SB (26.3 +/- 7.8 mol/L) and LRSB (16.3 +/- 1.0 mol/L) (p = not
      significant). CONCLUSION: This is the first description of a large-animal model
      to evaluate EDR after hemorrhagic shock. Resuscitation with LR requires
      significantly larger volumes than SB or LRSB. LR resuscitation leads to
      endothelial dysfunction, as determined by decreased EDR, versus SB or LRSB.
      Resuscitation with blood products may preserve nitric oxide bioactivity when
      compared with crystalloid resuscitation in the setting of hemorrhagic shock.

PMID- 16294067
TI  - Mild hypothermia improves survival after prolonged, traumatic hemorrhagic shock
      in pigs.
AB  - INTRODUCTION: Clinical studies have demonstrated improved survival after cardiac
      arrest with induction of mild hypothermia (34 degrees C). Infusion of ice-cold
      saline seems beneficial. The American Heart Association recommends therapeutic
      hypothermia for comatose survivors of cardiac arrest. For hemorrhagic shock (HS),
      laboratory studies suggest that mild hypothermia prolongs the golden hour for
      resuscitation. Yet, the effects of hypothermia during HS are unclear since
      retrospective clinical studies suggest that hypothermia is associated with
      increased mortality. Using a clinically relevant, large animal model with trauma
      and intensive care, we tested the hypothesis that mild hypothermia, induced with
      intravenous cold saline (ice cold or room temperature) and surface cooling, would
      improve survival after HS in pigs. METHODS: Pigs were prepared under isoflurane
      anesthesia. After laparotomy, venous blood (75 mL/kg) was continuously withdrawn
      over 3 hours (no systemic heparin). At HS 35 minutes, the spleen was transected.
      At HS 40 minutes, pigs were divided into three groups (n = 8, each): 1)
      Normothermia (Norm)(38 degrees C), induced with warmed saline; 2) Mild
      hypothermia (34 degrees C) induced with i.v. infusion of 2 degrees C saline (Hypo
      Ice) and surface cooling; and 3) Mild hypothermia (34 degrees C), induced with
      room temperature (24 degrees C) i.v. saline (Hypo-Rm) and surface cooling. Fluids
      were given when mean arterial pressure (MAP) was <30 mmHg. At HS 3 hours, shed
      blood was returned and splenectomy was performed. Intensive care was continued to
      24 hours. RESULTS: At 24 hours, there were two survivors in the Norm group, four
      in the Hypo-Ice group and seven in the Hypo-Rm group (p < 0.05 versus the Norm
      group, Log Rank). Time required to achieve 34 degrees C was 17 +/- 9 minutes in
      the Hypo-Ice group and 15 +/- 4 minutes in the Hypo-Rm group (NS). Compared with
      the Hypo-Rm group, the Hypo-Ice group required less saline during early HS (321
      +/- 122 versus 571 +/- 184 mL, p < 0.05). The Hypo-Ice group also had higher
      lactate levels than the Hypo-Rm group (p < 0.05). Hypothermia did not cause any
      increase in bleeding compared with normothermia. CONCLUSION: Mild hypothermia
      during HS, induced by infusion of room temperature saline and surface cooling,
      improves survival in a clinically relevant model of HS and trauma. However, the
      use of iced saline in this model had detrimental effects and did not cool the
      animal more quickly than room temperature fluids. These findings suggest that
      optimal methods for induction of hypothermia need to be addressed for each
      potential indication, e.g. cardiac arrest versus HS.

PMID- 16294068
TI  - Cyclic nucleotide second messengers (cAMP and cGMP) play a central role in signal
      transduction and regulation of mesenteric postcapillary fluid leak.
AB  - BACKGROUND: Endothelial cell receptors involved in post-injury/sepsis fluid
      extravasation are coupled to G-proteins that stimulate production of cGMP and
      cAMP. We hypothesize that cGMP and cAMP are endothelial second messengers that
      control microvascular permeability. The purposes of this series of experiments
      are to determine microvascular permeability under the following conditions: 1)
      reduced cGMP levels, 2) elevated cGMP levels, 3) reduced cAMP levels, and 4)
      elevated cAMP levels. METHODS: Rat mesenteric venules were cannulated and
      hydraulic permeability (Lp) was measured at 3 to 5 minute intervals during 1)
      cGMP synthesis inhibition, 2) inhibition of cGMP degradation, 3) cAMP synthesis
      inhibition, and 4) inhibition of cAMP degradation (n = 6 in each study group). Lp
      units are x10 cm(-7)/sec/cmH2O and represented as mean +/- SEM. RESULTS: Compared
      with baseline Lp (1.10 +/- 0.06), reduced cGMP levels by inhibiting its synthesis
      decreased Lp by over 50% (0.50 +/- 0.02, p < 0.001), while elevated cGMP levels
      by preventing its degradation increased Lp by more than 2-fold (0.91 +/- 0.10 to
      2.26 +/- 0.15, p < 0.001). The reduction of cAMP levels by synthesis inhibition
      elevated Lp over 400% from 0.92 +/- 0.04 to 4.11 +/- 0.54 (p < 0.001), and
      elevation of cAMP level by blocking its degradation reduced Lp almost 50% from
      1.11 +/- 0.04 to 0.59 +/- 0.06 (p < 0.001). CONCLUSIONS: The second messengers,
      cGMP and cAMP, contribute to the control mechanisms that govern fluid leak across
      the endothelial barrier: cGMP increases microvascular permeability, while cAMP
      decreases microvascular permeability. Endothelial cell cyclic nucleotide second
      messengers are pharmacologically accessible and may be targeted during post
      injury/sepsis-associated microvascular fluid leak.

PMID- 16294069
TI  - The balance between expression of intranuclear NF-kappaB and glucocorticoid
      receptor in polymorphonuclear leukocytes in SIRS patients.
AB  - BACKGROUND: We previously reported enhanced expression of nuclear factor kappa B
      (NF-kappaB) in activated polymorphonuclear leukocytes (PMNLs) from patients with
      systemic inflammatory response syndrome (SIRS). Inflammatory response, however,
      is not regulated only by stimulatory transcription factors. Glucocorticoid
      receptor (GR) has been recently reported to play an important role in anti
      inflammatory signal transduction. The objective of our study was to evaluate the
      balance between expression of intranuclear NF-kappaB and GR in PMNLs from SIRS
      patients. METHODS: In study 1, 29 patients with severe SIRS, who fulfilled the
      criteria for SIRS and had a serum C-reactive protein level of more than 10 mg/dL,
      were included. Expression of intranuclear NF-kappaB and GR in PMNLs was measured
      by flow cytometry with antibodies specific for NF-kappaB subunit p65 and GR. PMNL
      oxidative activity and serum cytokine levels were also measured. Study 2 included
      13 patients with severe trauma (Injury Severity Score 24.6 +/- 12.2). We measured
      serial changes in expression of intranuclear NF-kappaB and GR in days 0 to 2, 3
      to 6, and 7 to 14 after injury. RESULTS: In study 1, expression of both
      intranuclear NF-kappaB and GR in PMNLs was significantly higher in SIRS patients
      than in healthy controls. There was a strong correlation between expression of
      these two transcription factors (r = 0.78). Positive correlations were also found
      between PMNL oxidative activity and both transcription factors. In study 2,
      expression of both NF-kappaB and GR in PMNLs was markedly elevated on days 3 to 6
      after injury and changed serially with strong mutual correlation. CONCLUSIONS: In
      activated PMNLs from SIRS patients, levels of both intranuclear NF-kappaB and GR
      were elevated and strongly correlated. In trauma patients, NF-kappaB and GR in
      PMNLs changed serially with strong mutual correlation. Further studies are needed
      to clarify the effect of the balance of NF-kappaB and GR on PMNL activation and
      systemic inflammatory process.

PMID- 16294070
TI  - Comparison of peripheral metabolic effects of insulin and metformin following
      severe burn injury.
AB  - OBJECTIVE: Both insulin and metformin have been shown to attenuate hyperglycemia
      and reduce net muscle protein catabolism following burn injury. The purpose of
      this study was to compare the peripheral metabolic effects of insulin and
      metformin in severe burn patients. METHODS: Six adult patients with burns greater
      than 40% of their body surface underwent metabolic evaluation utilizing isotopic
      dilution of phenylalanine, femoral arterial and venous blood sampling, and
      sequential biopsies of leg muscle. Following baseline measurements, insulin was
      infused into the femoral artery at 0.45 mIU/min 100 mL leg volume. Patients were
      then given metformin (850 mg every 8 hours) for seven days with repeat metabolic
      evaluation before and during intra-arterial infusion of insulin. RESULTS: Intra
      arterial administration of insulin significantly increased insulin concentrations
      within the femoral vein, creating hyperinsulinemia localized to the extremity.
      Metformin had no significant effect on either peripheral glucose clearance or the
      rate of glucose oxidation. Furthermore, the availability of ATP and energy charge
      within muscle was not overtly affected by either insulin or metformin. Metformin
      did significantly increase the fractional synthetic rate of muscle protein which
      increased even further with insulin administration. Both metformin and insulin
      separately increased the rate of muscle protein synthesis as calculated using
      three compartment modeling. CONCLUSION: This study demonstrates a significant
      anabolic effect on muscle protein with metformin and a modest response with
      insulin. Findings also suggest that metformin and insulin may work
      synergistically to further improve muscle protein kinetics.

PMID- 16294071
TI  - Old fashion clinical judgment in the era of protocols: is mandatory chest X-ray
      necessary in injured patients?
AB  - BACKGROUND: The ATLS Course advocates that injured patients have a chest x-ray
      (CXR) to identify potential injuries. The purpose of this study was to correlate
      clinical indications and clinician judgment with CXR results to ascertain if a
      selective policy would be beneficial. METHODS: Patients treated at a Level I
      trauma center over 12 months were prospectively evaluated. Before obtaining a
      CXR, signs, symptoms, and history suggestive of thoracic injury were identified.
      Additionally, a trauma surgeon (TS) recorded whether in their judgment a CXR was
      clinically indicated. These findings were compared with final CXR diagnoses. The
      sensitivity of individual clinical indicators, combinations of clinical
      indicators, and TS judgment for CXR abnormalities were calculated with a 95%
      confidence interval. RESULTS: During the twelve-month study period, data were
      acquired on 772 patients (age 0-102 years). Seventy percent were male and 86.0%
      were injured by blunt force. Only 29% (N = 222) of the patients manifested one or
      more of the clinical indicators (signs and symptoms). The negative predictive
      value for the TS judgment was 98.2% which was superior to the clinical
      indicators. Reliance on the opinion of the TS to determine the need for a CXR
      would have eliminated 49.9% of CXRs and avoided hospital and radiologist reading
      charges totaling $100,078.22. CONCLUSION: Mandatory CXR for all trauma patients
      has a low yield for abnormal findings. A selective policy relying on surgical
      judgment guided by clinical indicators is safe and efficacious while reducing
      cost and conserving resources.

PMID- 16294073
TI  - Low-flow transtracheal rescue insufflation of oxygen after profound desaturation.
AB  - BACKGROUND: The objective of this study was to determine whether low-flow
      transtracheal insufflation of oxygen (TRIO) could rescue an animal from profound
      desaturation. This temporizing maneuver could be useful during cannot-intubate or
      -ventilate scenarios by resolving hypoxia without the morbidity associated with
      more invasive procedures. METHODS: Seven swine for a total of 12 runs were
      studied. Animals were pharmacologically anesthetized, paralyzed, and mechanically
      ventilated with room air. After disconnection from the ventilator and
      desaturation to an Spo2 < 50%, low-flow TRIO (2 L/min) was administered for 1
      hour. RESULTS: All animals survived and Spo2 increased to greater than 90% in 23
      seconds on average. Pao2 (mean, 183 mm Hg) remained elevated throughout the
      study. Hemodynamic stability was maintained for at least 15 minutes. CONCLUSION:
      Low-flow TRIO rescued animals from profound hypoxia and maintained oxygenation
      for at least 1 hour. Low-flow TRIO did not prevent hypercarbia with its
      subsequent sympathetic activation.

PMID- 16294072
TI  - Prone positioning improves oxygenation in post-traumatic lung injury--a
      prospective randomized trial.
AB  - BACKGROUND: In a prospective randomized trial the effect of prone positioning on
      the duration of mechanical ventilation was evaluated in multiple trauma patients
      and was compared with patients ventilated in supine position. METHOD: Multiple
      trauma patients of the intensive care units of two university hospitals were
      considered eligible if they met the criteria for acute lung injury or the acute
      respiratory distress syndrome. Patients in the prone group (N = 21) were kept
      prone for at least eight hours and a maximum of 23 hours per day. Prone
      positioning was continued until a PaO2:FiO2 ratio of more than 300 was present in
      prone as well as supine position over a period of 48 hours. Patients in the
      supine group (N = 19) were positioned according to standard care guidelines.
      RESULTS: The duration of ventilatory support did not differ significantly (30 +/-
      17 days in the prone group and 33 +/- 23 days in the supine group). Worst case
      analysis (death and deterioration of gas exchange) displayed ventilatory support
      for 41 +/- 29 days in the prone group and 61 +/- 35 days in the supine group (p =
      0.06). The PaO2:FiO2 ratio increased significantly more in the prone group in the
      first four days (p = 0.03). The prevalence of Acute Respiratory Distress Syndrome
      (ARDS) following acute lung injury (p = 0.03) and the prevalence of pneumonia (p
      = 0.048) were reduced also. One patient in the prone and three patients in the
      supine group died due to multi organ failure (p = 0.27). CONCLUSIONS:
      Intermittent prone positioning was not able to reduce the duration of mechanical
      ventilation in this limited number of patients. However the oxygenation improved
      significantly over the first four days of treatment, and the prevalence of ARDS
      and pneumonia were reduced.

PMID- 16294074
TI  - Halo vest immobilization in the elderly: a death sentence?
AB  - BACKGROUND: Cervical spine fractures (CSFs) in elderly patients are increasingly
      common as the population ages. In many centers, halo vest immobilization (HVI) is
      the treatment of choice. Our anecdotal experience suggested that elderly patients
      treated with HVI have frequent bad outcomes. The purpose of this study was to
      compare the outcomes of elderly and younger CSF patients as related to treatment
      (HVI, surgery, or hard collar). METHODS: Registry data from our Level I trauma
      center were reviewed to identify patients admitted with CSFs during an 80-month
      period. We excluded those with Glasgow Coma Scale (GCS) score of 3 at admission
      or death within 24 hours of admission. Patients were grouped as OLD (aged > or =
      66 years) or YNG (aged 18-65 years). Data were compared using chi and Student's t
      test, with p < 0.05 considered statistically significant. RESULTS: One hundred
      twenty-nine OLD (aged 79.7 +/- 0.7 years) and 289 YNG (aged 38.3 +/- 0.8 years)
      patients met study criteria. Injury Severity Score was higher in YNG (18.9 +/-
      0.8 vs. 14.8 +/- 1.0, p < 0.05), and GCS score was the same (OLD, 13.7 +/- 0.2;
      YNG, 13.0 +/- 0.2; p = 0.06) in both, but mortality was higher in OLD patients
      (21% vs. 5%, p < 0.05). OLD HVI patients had higher mortality than YNG HVI (40%
      vs. 2%). Among OLD patients, age, Injury Severity Score, GCS, and number of
      comorbidities were the same for each treatment subgroup. Despite this, mortality
      for the HVI subgroup was higher than either the surgery or collar subgroup. Of
      the OLD HVI patients that died, 14 died with pneumonia and 10 had a cardiac or
      respiratory arrest that preceded death. CONCLUSION: OLD patients with CSFs have
      higher mortality than YNG. HVI in OLD patients is associated with the worst
      outcomes, irrespective of injury severity, and should be considered a last
      resort. Further study is warranted to determine the optimal treatment for CSF in
      OLD patients.

PMID- 16294076
TI  - Suture line failure in intra-abdominal colonic trauma: is there an effect of
      segmental variations in blood supply on outcome?

PMID- 16294077
TI  - Effects of escharotomy as abdominal decompression on cardiopulmonary function and
      visceral perfusion in abdominal compartment syndrome with burn patients.
AB  - BACKGROUND: Abdominal compartment syndrome (ACS) can become fatal; however, it
      has rarely been described as a complication of burn injury. This study clarified
      the physiologic results of abdominal decompression (AD) for ACS in patients with
      burn injury in detail. METHODS: Extensively burned patients admitted to our burn
      unit between January 2003 and February 2004 were prospectively monitored by
      pulmonary artery catheter. Physiologic parameters from the catheter, blood gas
      analysis, intrabladder pressure as a parameter of intra-abdominal pressure (IAP),
      peak inspiratory pressure, and urine output (UO) were compared before and after
      escharotomy as AD in patients with ACS. RESULTS: Eight of 36 patients who had
      sustained more than 30% total body surface area burn developed ACS requiring AD
      in 18.3 +/- 4.9 hours. AD significantly decreased IAP (52 +/- 9 cm H2O vs. 26 +/-
      7 cm H2O), peak inspiratory pressure (53 +/- 13 cm H2O vs. 35 +/- 6 cm H2O),
      heart rate, and Paco2, and increased cardiac index (1.6 +/- 0.7 L/min/m2 vs. 2.5
      +/- 0.9 L/min/m2), abdominal perfusion pressure (50 +/- 11 mm Hg vs. 72 +/- 17 mm
      Hg), UO (0.45 +/- 0.46 mL/h/kg vs. 2.0 +/- 2.1 mL/h/kg), and oxygen delivery
      index (290 +/- 195 mL/m2/min vs. 455 +/- 218 mL/m2/min). Impaired oxygen
      consumption index increased (86 +/- 43 mL/m2/min vs. 153 +/- 58 mL/m2/min) after
      AD. CONCLUSION: In patients with severe burn injury, elevated IAP makes pulmonary
      artery wedge pressure and UO unreliable indices of preload or intravascular
      volume, and decreases abdominal perfusion in the resuscitation period. AD in
      these patients significantly improves the ventilation, hemodynamic parameters,
      and oxygen metabolism.

PMID- 16294078
TI  - Reversal of anticoagulation in trauma: a North-American survey on clinical
      practices among trauma surgeons.
AB  - BACKGROUND: Recent studies addressing reversal of anticoagulation in trauma have
      reported conflicting results. We hypothesized that current clinical practice is
      variable throughout North America. METHODS: We surveyed 100 trauma surgeons to
      obtain information regarding variability in current clinical practice. RESULTS:
      Seventy-five of 100 trauma surgeons surveyed responded, and the majority (98.7%)
      agreed that preinjury anticoagulation poses problems in trauma management that
      include bleeding, increased complications, and mortality. Nine participants
      (12.2%) had a protocol addressing reversal of anticoagulation in their
      institution. Most use fresh frozen plasma based on the type and location of
      injury, initial international normalized ratio (INR), and targeted INR value.
      Fresh frozen plasma was consistently used in patients with positive head computed
      tomographic scans, hemothorax, nonoperative solid organ injury management, pelvic
      and long bone fractures, and any operative intervention. Practice inconsistencies
      were found in patients with loss of consciousness and normal head computed
      tomographic scan, facial and rib fractures, and pulmonary contusion. Significant
      variability was found in the reversal INR target. One third of participants
      agreed that anticoagulation could be restarted 5 to 7 days after craniotomy; one
      sixth would do so within 72 hours and one third would wait 10 or more days. Most
      agreed that anticoagulation could be restarted 3 days after chest, abdominal, and
      orthopedic operations. Significant inconsistencies were also observed regarding
      when to restart anticoagulation in closed head injury patients treated
      nonoperatively. CONCLUSION: On the basis of the discrepancies observed in this
      survey, a clinical trial addressing specific injury location and patterns, INR
      thresholds, and type of strategy to achieve reversal is warranted, and most would
      agree to participate.

PMID- 16294079
TI  - A prospective randomized trial of nebulized morphine compared with patient
      controlled analgesia morphine in the management of acute thoracic pain.
AB  - BACKGROUND: Successfully managing pain for the trauma patient decreases
      morbidity, improves patient satisfaction, and is an essential component of
      critical care. Using patient-controlled analgesia (PCA) morphine to control pain
      may be complicated by concerns of respiratory depression, hemodynamic
      instability, addiction, urinary retention, and drug-induced ileus. Morphine is
      rapidly absorbed by mucosal surfaces in the respiratory tract, achieving systemic
      concentrations equal to 20% of equivalent intravenous doses. The purpose of this
      study was to evaluate the safety, efficacy, and utility of nebulized morphine in
      patients with posttraumatic thoracic pain. METHODS: This double-blinded,
      prospective study randomized patients with severe posttraumatic thoracic pain
      into two groups. The experimental group (NMS) received nebulized morphine every 4
      hours and normal saline by PCA. The control group (PCA) received nebulized saline
      every 4 hours and morphine by PCA. Dose adjustments were made based on patient
      response to treatments using a 10-point visual analog scale (VAS) for pain.
      Pulmonary function, pain relief (VAS), level of sedation (0-3), total drug
      administration, and systematic side effects were recorded. RESULTS: Forty-four
      patients were randomized (22 per group). Seven hundred seventy observations were
      made. The mean 4-hour dose of morphine was 11.96 +/- 3.4 mg for NMS and 6.22 +/-
      4.7 mg for PCA (p < 0.001). Patients with NMS had lower heart rates compared with
      PCA (79 +/- 11 bpm versus 92 +/- 12 bpm; p < 0.001) and were less sedated (0.33
      +/- 0.7 versus 0.56 +/- 0.9; p = 0.03). The mean pain level (VAS) was 3.38 +/-
      1.8 for NMS and 3.84 +/- 2.7 for PCA (p = 0.2). There was no difference between
      pain levels before and after dosing. There were no differences between groups
      with respect to arterial blood pressure, respiratory rate, vital capacity, mean
      forced expiratory volume in 1 second, spirometric volumes, or Sao2. CONCLUSION:
      Nebulized morphine can be safely and effectively used to control posttraumatic
      thoracic pain. Pain can be successfully managed while vital capacity, mean forced
      expiratory volume in one second, and spirometric volumes are maintained. Compared
      with PCA morphine, nebulized morphine provides equivalent pain relief with less
      sedative effects.

PMID- 16294080
TI  - What price for general surgery?
AB  - BACKGROUND: This study aims to determine the cost-benefit analysis of adding a
      full emergency general surgery (EGS) arm to a trauma/critical care (TCC) service
      with limited EGS activity in a Level I trauma center. METHODS: Data on the
      composition, activity, and billings of a TCC were collected and compared before
      (January 1, 2002-June 30, 2003) and after (July 1, 2003-December 31, 2003) it
      assumed the care of all unassigned EGS patients. These included patient volume
      and demographics, service, procedures, on-call/service activity, and professional
      billings and collections. Data are means +/- SD or percentages. Intergroup
      comparisons were performed by using t test or chi2 as appropriate; significance
      was assumed for values of p < 0.05. RESULTS: Deploying an EGS arm increased
      coverage weeks (+52 weeks) and necessitated additional staffing (pre-EGS, n = 5;
      post-EGS, n = 6). Trauma operative volume remained constant (8.2 vs. 10.3 per
      month), EGS and elective case load increased (28.7 vs. 60 per month; p < 0.01),
      and the EGS case/consult ratio decreased from 0.81 to 0.64 (p < 0.01). This
      expanded activity was associated with reduced on-call nonclinical hours, from 3.2
      +/- 0.9 to 1.1 +/- 0.8 (p < 0.01), and increased outpatient visits (68.6 vs. 91.1
      per month; p < 0.01) and off-service time used for elective operations (22.3 vs.
      76%; p < 0.01). Billings significantly increased in each arm compared with the
      pre-EGS study period (operating room, +44.8; intensive care unit, +12.5;
      outpatient, +48.7%; p < 0.01). CONCLUSION: Integrating a full EGS into a TCC
      service encumbers increased nontrauma unscheduled clinical activity in the
      operating room, clinic, and floors, which resulted in enhanced billings. These
      beneficial effects were accrued at the expense of individual time and investment
      in recruiting additional faculty.

PMID- 16294081
TI  - Use of goniometry to predict inadequate flexion-extension roentgenograms: a
      preliminary study.
AB  - BACKGROUND: Flexion-extension roentgenograms (FER) of the cervical spine are
      often inadequate because of limited range of motion (ROM). The purpose of this
      study was to determine the utility of goniometry to predict a patient's ability
      to achieve sufficient ROM to obtain adequate FER. METHODS: We evaluated 65
      consecutive blunt trauma patients undergoing evaluation by FER in the emergency
      department. Patients were evaluated by goniometry before performing FER. Adequate
      ROM was defined as flexion and extension of >30 degrees from neutral. RESULTS:
      Seventy-five percent of patients had adequate FER. All of these patients were
      predicted to have sufficient ROM by goniometry. Goniometry predicted limited ROM
      in 69% of patients who had inadequate FER. The positive predicative value of
      goniometry in predicting inadequate FER was 100%. The incidence of cervical spine
      injuries was 44% in patients with inadequate ROM by goniometry and 23.0% in
      patients with inadequate FER (versus 7.69% in patients with adequate FER).
      CONCLUSION: Goniometry accurately predicted those patients who were unable to
      achieve sufficient ROM for adequate FER. Patients with inadequate FER were at a
      higher risk for cervical spine injury compared with patients with adequate FER
      (23.0 versus 7.69%). Early identification of these patients will help limit the
      number of inadequate studies obtained and expedite evaluation of high-risk
      patients.

PMID- 16294082
TI  - The effect of acute smoking on spinal fusion: an experimental study among
      rabbits.
AB  - BACKGROUND: The establishment of an environment to force animals to inspire
      cigarette smoke is mandatory to study the true effects of smoking. This model has
      been used to study long-bone healing but has not yet been used to study spinal
      fusion. METHODS: Forty male rabbits were divided into four equal groups. All the
      animals underwent bilateral intertransverse-process fusion at L5-L6 using the
      1995 fusion model of Boden et al. The first (C8-week) group did not undergo
      cigarette smoke inhalation and individual rabbits were killed at 8 weeks; the
      second (S8-week) group underwent intermittent cigarette smoke inhalation and
      individual rabbits were killed at 8 weeks; the third (C6-week) group did not
      undergo cigarette smoke inhalation, and animals were killed at 6 weeks; and the
      fourth (S6-week) group underwent intermittent smoke inhalation and group-included
      rabbits were killed at 6 weeks. Subsequent to the animals having been killed, the
      fusion masses were harvested for a series of studies including manual palpation,
      biomechanical testing, radiographic examination, and histologic analysis.
      RESULTS: Six rabbits died shortly after the operation. Of the remaining 34
      rabbits, the lumbar spine specimen was harvested for study. Manual palpation,
      radiographic examination, and histologic analysis of the fusion masses revealed
      no statistically significant difference in fusion results between the control and
      the corresponding smoking group killed at either 8 weeks or 6 weeks.
      Biomechanical testing of the fusion masses also revealed no statistically
      significant difference in fusion results between the control and the smoking
      group killed at 8 weeks, although it did indicate that smoking resulted in a 44%
      decrease in mean flexion stiffness and a 32% decrease in mean extension stiffness
      among the animals killed at 6 weeks. The former (decrease in flexion stiffness)
      was statistically significant (p < 0.05). CONCLUSION: The results of the
      biomechanical testing conducted as a part of the current study demonstrate that
      acute cigarette smoke inhalation delays but does not prevent the spinal fusion
      process for rabbits.

PMID- 16294083
TI  - Damage control orthopedics in patients with multiple injuries is effective, time
      saving, and safe.
AB  - BACKGROUND: Although early fracture fixation is expedient in patients with
      multiple injuries, early total care (ETC) may be associated with posttraumatic
      systemic complications. This study was conducted to prospectively evaluate the
      concept of damage control by immediate external fracture fixation (damage control
      orthopedics [DCO]) and consecutive conversion osteosynthesis with regard to time
      savings, effectiveness, and safety. METHODS: In a prospective controlled trial, a
      cohort of 1,070 patients with an Injury Severity Score (ISS) of 20.7 were
      admitted to a Level I trauma center over a 3.5-year period. Patients with an ISS
      > 15, survival of more than 24 hours, and without interhospital transfer were
      included. In all patients with major fractures requiring immediate stabilization,
      external fixation was performed (DCO). Conversion was executed at the earliest
      possible time as a one-stage procedure after stabilization of organ functions.
      TRISS was calculated for patients requiring DCO (DCO group) and for patients
      without major fractures (control group). Time spent on particular and all
      surgical procedures, blood loss, and complications of DCO were compared with data
      of consecutive conversion osteosyntheses which were considered as hypothetical
      ETC procedures (h-ETC) in identical patients. RESULTS: Four hundred nine patients
      fulfilled the inclusion criteria. Seventy-five (ISS of 37.3) required DCO for 135
      fractures, whereas 334 patients (ISS of 30.4) did not require immediate fracture
      fixation. Mean surgical time was 62 +/- 30 minutes (SEM, 3.5) for DCO. Because of
      fracture consolidation with external fixation (n = 3) and injury-related death (n
      = 15), conversion (h-ETC) was performed in 57 patients for 101 fractures.
      Duration of external fixation averaged 13.7 days (range, 3-46 days). Fifty-five
      patients (96.5%) required intensive care treatment and 42 patients (73.7%)
      required mechanical ventilation at the time of conversion. Mean operation time
      for conversion was 233 +/- 19 minutes (SEM, 18.7) with a value of p < 0.001.
      Also, blood loss was significantly (p < 0.001) different for DCO (<50 mL) and h
      ETC (472 mL; SEM, 63). Pin-track infections were identified in five patients, two
      patients with acetabular plate osteosynthesis had deep wound infection, and one
      patient died related to bacterial sepsis with infections of all wound sites.
      Overall mortality in DCO patients was significantly lower than predicted by TRISS
      (20% vs. 39.3%), as it was in the 334 patients without immediate fracture
      fixation (29.5% vs. 24.3%). CONCLUSION: DCO appears to provide a major reduction
      of operation time and blood loss in the primary treatment period in severely
      injured patients compared with h-ETC. In addition, we found that DCO is not
      associated with an increased rate of procedure-related complications. So far, DCO
      with early and one-stage conversion seems to be a safe strategy of primary
      fracture treatment in patients with multiple injuries.

PMID- 16294085
TI  - Functional outcome after operative treatment of eight type III coronoid process
      fractures.
AB  - BACKGROUND: There have been few reports about surgical outcomes of coronoid
      process fractures. Eight cases of clinical results of type III coronoid process
      fractures were reviewed. METHODS: Eight patients with coronoid type III fracture
      were retrospectively reviewed. All were men with an average age of 33 years.
      There were three isolated fractures, two elbow dislocations, two radial head and
      neck fractures, and one medial collateral ligament rupture. An open reduction and
      internal fixation through an anterior approach with cannulated screws was used.
      The patients were followed up for a mean of 31 months (range, 24-60 months).
      RESULTS: Average active elbow joint motion at the most recent follow-up was 105
      degrees. The average Mayo Elbow Performance Score was 76.9 (range, 50-95). Of the
      results, there was one excellent, four good, two fair, and one poor. CONCLUSION:
      Early open reduction and stable internal fixation provided a reliable method for
      the treatment of type III coronoid process fractures. Any associated injuries to
      the elbow and fracture comminution were considered as important prognostic
      factors.

PMID- 16294087
TI  - Percutaneous plate stabilization of proximal tibial fractures.
AB  - BACKGROUND: Despite various treatment methods, proximal tibial fractures are
      common injuries associated with poor outcomes and high rates of complications. To
      improve this, a percutaneous plating technique was performed to treat proximal
      tibial fractures. METHODS: Twenty-four proximal tibial fractures (17 proximal
      fractures [AO 41] and 7 proximal shaft fractures [AO 42]) were treated using
      percutaneous plating with either or both sides without bone graft. One was an
      open fracture. RESULTS: All fractures healed. The average time for fracture
      healing was 16.5 weeks (range, 8-24 weeks). Complications included one case of
      shortening (1 cm) and two cases of malalignments; one valgus of 6 degrees and one
      varus of 5 degrees. There was one case of superficial infection that was healed
      after removal, but no patient showed deep infection. Results were evaluated by
      the modified Rasmussen scoring system. Most patients had excellent or good
      results; only one patient had fair results. CONCLUSION: Minimally invasive
      percutaneous plating can provide favorable results in the treatment of proximal
      tibial fractures.

PMID- 16294086
TI  - Function impairment and pain after closed treatment of fractures of the
      mandibular condyle.
AB  - BACKGROUND: To determine the prognosis of fractures of the mandibular condyle
      after closed treatment. METHODS: Patients (n = 144) with a fracture of the
      mandibular condyle, all treated closed, were included in the study. Fracture
      types and position of the fracture parts were determined on radiographs. Follow
      up was after 12 months in which the average pain, experienced during the last
      week (visual analog scale, 100 mm), and mandibular functioning were assessed
      (mandibular function impairment questionnaire (MFIQ)). RESULTS: Data of 116 (81%)
      patients, 41 women (35%) and 75 men (65%), were available for analysis. Condylar
      neck fractures were most common (52%). Bilateral fractures were present in 28% of
      the patients. Pain (visual analog scale score >0) was found in 9% of the
      patients. Impaired mandibular function was found in 40% (MFIQ >0) and 24% (MFIQ >
      or =4) of the patients. The most important risk factor for pain was being a
      woman. The most important risk factors for function impairment were > or =25
      years of age and gross displacement of the fracture parts. CONCLUSION: The
      overall prognosis of mandibular function and pain after closed treatment of
      condylar fractures is good. The most important risk factor for pain persisting
      for 1 year after closed treatment of a condylar fracture is being a woman. The
      most important risk factors for function impairment are an age of > or =25 years
      and gross displacement of the fracture parts.

PMID- 16294088
TI  - Comminuted diaphyseal fractures of the radius and ulna: does bone grafting affect
      nonunion rate?
AB  - BACKGROUND: The recommendation of Anderson and colleagues to bone graft even
      relatively minor amounts of comminution (a third of the bone diameter) in the
      treatment of diaphyseal forearm fractures with plate-and-screw fixation has been
      questioned. This study examines factors related to nonunion in adult patients
      with comminuted diaphyseal fractures of both the radius and the ulna to determine
      the relative influence of bone grafting. METHODS: Over a 15-year period at two
      hospitals, 41 patients with diaphyseal fractures of both forearm bones satisfied
      the following criteria: comminution (Orthopaedic Trauma Association grade IV or
      higher) of at least one fracture; treatment with 3.5- or 4.5-mm dynamic
      compression plates at least six holes in length; and minimum 12-month follow-up.
      Multiple logistic regression was used to determine the contribution of the
      following factors to the risk of nonunion: multiple injuries; ipsilateral upper
      extremity injury; open wound; and the application of cancellous bone graft at the
      fracture site. RESULTS: Five patients had nonunion of one or both bones (12%).
      According to the multiple logistic regression model, none of the factors studied
      had a statistically significant association with nonunion (p > 0.40 for all). The
      odds ratios were as follows: multiple injuries, 2.1 (95% confidence interval
      [CI], 0.34-12.9); ipsilateral injury, 0.68 (95% CI, 0.058-7.84); open fracture,
      1.46 (95% CI, 0.21-9.89); and bone graft, 0.98 (95% CI, 0.15-6.42). CONCLUSION:
      Nonunion occurred in 12% of comminuted, diaphyseal fractures of both bones of the
      forearm treated with dynamic compression plates. No single factor was associated
      with nonunion. In particular, the use of bone graft was not associated with a
      higher rate of union.

PMID- 16294090
TI  - Direct health care costs after traumatic spinal cord injury.
AB  - BACKGROUND: The objective was to quantify direct health care costs attributable
      to traumatic spinal cord injury (SCI). METHODS: This population-based cohort
      study followed individuals with SCI from date of injury to 6 years postinjury.
      SCI cases were matched to a comparison group randomly selected from the general
      population. Administrative data from a Canadian province with a universal
      publicly funded health care system and centralized health databases were used.
      Costs included hospitalizations, physician services, home care, and long-term
      care. RESULTS: Attributable costs in the first year were $121,600 (2002 $CDN) per
      person with a complete SCI, and $42,100 per person with an incomplete injury. In
      the subsequent 5 years, annual costs were $5,400 and $2,800 for persons with
      complete and incomplete SCIs, respectively. CONCLUSION: Direct costs in the first
      year after SCI are substantial. In the subsequent 5 years, individuals with SCI
      will continue to accrue greater costs than the general public.

PMID- 16294091
TI  - Mercaptoethylguanidine inhibition of inducible nitric oxide synthase and
      cyclooxygenase-2 expressions induced in rats after fluid-percussion brain injury.
AB  - The present study examined the temporal expression of nitric oxide synthase
      (iNOS) and cyclo-oxygenase (COX)-2 in rat brains after traumatic brain injury
      (TBI). We studied the effects of mercaptoethylguanidine (MEG), a dual inhibitor
      of the inducible iNOS and COX with scavenging effect on peroxynitrite, on
      physiologic variables, brain pathogenesis, and neurologic performance in rats
      after a lateral fluid percussive-induced TBI. Mean arterial blood pressure and
      percentage cerebral tissue perfusion in MEG-treated TBI rats showed significant
      improvement when compared with TBI rats. Immunohistochemical analysis showed a
      marked number of iNOS and COX-2 immunopositive cells in the cerebral cortex
      ipsilateral to the injury in TBI rats when compared with MEG-treated TBI rats.
      MEG also significantly decreased the number of hyperchromatic and shrunken
      cortical neurons when compared with TBI rats' brain nitrate/nitrite, and
      prostaglandin E2 levels were attenuated in MEG-treated TBI rats when compared
      with TBI rats. It is therefore suggested that treatment of MEG via inhibition of
      iNOS and COX-2 might contribute to improved physiologic variables, neuronal cell
      survival, and neurologic outcome after TBI.

PMID- 16294092
TI  - Prehospital prediction of intensive care unit stay and mortality in blunt trauma
      patients.
AB  - BACKGROUND: The success of a trauma system relies on transfer of patients from
      the field to the most appropriate hospital for definitive care. However, no
      consensus has been reached regarding the best criteria or triage tool for
      identifying patients injured seriously enough to warrant transfer to a trauma
      center. METHODS: Predictors of mortality and intensive care unit stay were
      identified and prediction models developed in a design data set. The performance
      of these models was evaluated in a test data set and compared with current trauma
      triage guidelines, derived from the American College of Surgeons model. RESULTS:
      The newly developed prediction models performed comparably with the current
      trauma triage guidelines. CONCLUSION: Although the performance of newly developed
      triage models was promising, their performance did not exceed that of the current
      trauma triage guidelines. In particular, the anatomic injury criteria appeared to
      be the key component of the current trauma triage guidelines.

PMID- 16294093
TI  - Readiness to change and the role of inpatient counseling for alcohol/substance
      abusing youth with major trauma.
AB  - BACKGROUND: The data regarding trauma recidivism among youth suggest that alcohol
      and/or substance abuse counseling should be an integral part of an injury
      prevention program in Level I trauma centers. Analysis of attitudes and
      motivation toward changing substance use is an important part of counseling. This
      study explores the willingness of a patient population at risk for recurrent
      injury to address their alcohol or substance use habits. METHODS: Young patients
      (ages 15-24) admitted with major trauma and positive alcohol/toxicology screens
      to a Level I trauma center were offered a previously described "readiness-to
      change" interview tool. Responses were analyzed using a modified methodology to
      identify those patients motivated toward curtailing subsequent use. RESULTS: From
      February 2002 to August 2003, 120 patients (study group) consented to be
      interviewed. Within the study group, 109 (91%) were male patients, 110 (92%) were
      black, 85 (71%) suffered penetrating trauma injuries, and 75 (63%) had dropped
      out of high school. According to their interview tool responses, 61 (87%) of
      those patients using alcohol and 63 (85%) of those patients using drug were
      either "contemplative" or "action oriented" toward addressing their substance use
      behaviors. Furthermore, 35 patients (29%) in the study group indicated an
      absolute willingness to address their alcohol/drug use. No patient accessed
      treatment resources provided once discharged. CONCLUSION: Although findings
      regarding the assessment of attitudes toward readiness to change among young
      drug/alcohol-using patients experiencing penetrating trauma were initially very
      encouraging, facilitating and engaging these patients in actual behavior changing
      activities was far more challenging. Further exploration into the existing
      barriers to accessing treatment services and cultivating attitudes toward
      changing substance use behaviors is necessary.

PMID- 16294094
TI  - Pelvic circumferential compression in the presence of soft-tissue injuries: a
      case report.

PMID- 16294095
TI  - Removal of a broken intramedullary locking bolt during tibia nail exchange.

PMID- 16294096
TI  - Rectus abdominus myonecrosis: an unrecognized complication of rectus sheath
      hematoma.

PMID- 16294097
TI  - Partial pulmonary torsion after thoracotomy without pulmonary resection.

PMID- 16294098
TI  - Necrotizing fasciitis caused by Vibrio vulnificus: a review of four cases in a
      Singapore tertiary hospital.

PMID- 16294099
TI  - A follow-up analysis of factors associated with head-injury mortality after
      paramedic rapid sequence intubation.
AB  - BACKGROUND: The San Diego Paramedic Rapid Sequence Intubation (RSI) Trial
      documented an increase in mortality after paramedic RSI, with hyperventilation
      identified as a contributing factor in a small subgroup analysis. Here we explore
      factors affecting outcome in the entire cohort of patients undergoing paramedic
      RSI to confirm previous findings. This also represents a synthesis of findings
      from previous analyses METHODS: Adult trauma patients with severe head injury
      (Glasgow Coma Scale score, 3-8) who could not be intubated without RSI were
      prospectively enrolled in the trial. This analysis excluded patients without
      traumatic brain injury (head/neck abbreviated injury score <2 or failure to meet
      Major Trauma Outcome Study criteria) or death in the field or within 30 minutes
      of arrival. Each remaining trial patient was matched to two nonintubated
      historical controls from the county trauma registry based on: age, sex,
      mechanism, abbreviated injury scores for each body system, and Injury Severity
      Score. Logistic regression, cohort analysis, mean least squares regression, and
      discordant group analysis were used to explore the impact of various factors on
      outcome. RESULTS: Of the 426 trial patients, 352 met inclusion criteria for this
      analysis and were hand-matched to 704 controls. Trial patients and controls were
      identical with regard to all matching variables. Mortality was increased in RSI
      patients versus matched controls (31.8 versus 23.7%; odds ration, 1.5; 95%
      confidence interval, 1.1-2.0; p < 0.01). Hyperventilation was associated with an
      increase in mortality, whereas transport by aeromedical crews after paramedic RSI
      was associated with improved outcomes. The reported incidence of aspiration
      pneumonia was higher for the RSI patients. CONCLUSION: Paramedic RSI was
      associated with an increase in mortality compared with matched historical
      controls. The association between hyperventilation and mortality was confirmed.
      In addition, patients transported by helicopter after paramedic RSI had improved
      outcomes. Paramedic RSI did not seem to prevent aspiration pneumonia.

PMID- 16294100
TI  - Technical modification for second distal screw insertion for locked nailing.

PMID- 16294101
TI  - The literature increasingly supports expectant (conservative) management of renal
      trauma--a systematic review.
AB  - BACKGROUND: The perfect degree of operative intervention in renal trauma is
      unknown. However, expectant management for most blunt renal trauma is the
      standard of care, and nonoperative management is increasingly accepted for stab
      wounds. The best treatment of gunshot wounds and vascular injuries is still
      unclear; however, recent data indicates that a trial of nonoperative therapy may
      be warranted in those not exsanguinating from the kidney. Conservative management
      has many benefits, the greatest of which is decreasing the rate of iatrogenic
      nephrectomy. We have reviewed the world's literature to determine the level of
      support for expectant management of renal injury. METHODS: The English language
      literature concerning renal trauma was identified with the assistance of Medline,
      and additional cited works not picked up in the initial search were obtained. One
      hundred and ten citations were ultimately reviewed dating back to 1947. RESULTS:
      Most modern citations support at least a trial of expectant management for renal
      trauma patients not exsanguinating from the kidney, and without ureteral or renal
      pelvis injuries. The treatment of renovascular injuries has less consensus, but
      it appears that 'conservative' management by the application of nephrectomy is
      often the best approach, although renovascular repair may be attempted in rare
      cases. CONCLUSION: Dozens of papers going back as far as 50 years seem to support
      the wider use of nonoperative therapy of renal injuries, although for unclear
      reasons, this approach is not yet universally accepted.

PMID- 16294102
TI  - Respiratory failure by inhalation of a fire extinguisher.

PMID- 16294103
TI  - Use of non-invasive esophageal echo-Doppler system in the ICU: a practical
      experience.
AB  - In a recent issue of the Journal of Trauma, Kim et al. described their experience
      with the esophageal Doppler monitor (EDM) in major burn patients. Other authors
      have reported the historical development of the EDM, reviewed the technical and
      scientific aspects of this modality, and compared the EDM with the pulmonary
      arterial catheter (PAC). However, most studies exclude the bedside, practical
      aspects of EDM placement and use. We retrospectively reviewed our EDM utilization
      over the past 27 months, with emphasis on the practical aspects of its use,
      potential indications, and contraindications. The purpose of this paper is to
      share our EDM experience with the reader.

PMID- 16294104
TI  - The esophageal Doppler monitor is useful for fluid management during the
      perioperative and intensive care periods.

PMID- 16294105
TI  - Diagnosis of acid-base derangements and mortality prediction in the trauma
      intensive care unit: the physiochemical approach.

PMID- 16294107
TI  - Nonhelmeted motorcyclist: a burden to society? A study using the National Trauma
      Data Bank.

PMID- 16294111
TI  - A timely meeting: objective measurement of physical activity.

PMID- 16294112
TI  - The technology of accelerometry-based activity monitors: current and future.
AB  - PURPOSE: This paper reviews accelerometry-based activity monitors, including
      single-site first-generation devices, emerging technologies, and analytical
      approaches to predict energy expenditure, with suggestions for further research
      and development. METHODS: The physics and measurement principles of the
      accelerometer are described, including the sensor properties, data collections,
      filtering, and integration analyses. The paper also compares these properties in
      several commonly used single-site accelerometers. The emerging accelerometry
      technologies introduced include the multisensor arrays and the combination of
      accelerometers with physiological sensors. The outputs of accelerometers are
      compared with criterion measures of energy expenditure (indirect calorimeters and
      double-labeled water) to develop mathematical models (linear, nonlinear, and
      variability approaches). RESULTS: The technologies of the sensor and data
      processing directly influence the results of the outcome measurement (activity
      counts and energy expenditure predictions). Multisite assessment and combining
      accelerometers with physiological measures may offer additional advantages.
      Nonlinear approaches to predict energy expenditure using accelerometer outputs
      from multiple sites and orientation can enhance accuracy. CONCLUSIONS: The
      development of portable accelerometers has made objective assessments of physical
      activity possible. Future technological improvements will include examining raw
      acceleration signals and developing advanced models for accurate energy
      expenditure predictions.

PMID- 16294113
TI  - Principles of design and analyses for the calibration of accelerometry-based
      activity monitors.
AB  - The term "calibration" in accelerometry research has come to mean the conversion
      of counts into other established measurement units. In this article, two types of
      calibration research are described. Unit calibration (or interinstrument
      variability) is described as a reliability issue, whereas value calibration is
      described as more of a validity issue. Principles for design of accelerometry
      based validation studies are described to provide a guide for future calibration
      research. The population must be representative of the intended population in
      terms of demographics and size, monitors must be representative of the population
      of monitors that would be available, and activities in the protocol must be
      representative of the types of activities performed by the intended population.
      It is also important to employ appropriate analytical strategies in this type of
      research. A case study employing the appropriate design principles is included to
      demonstrate how results can vary depending on the type of analyses that are used.
      Direct comparisons are made between a mixed model regression approach and an
      approach based on receiver operator characteristic curves.

PMID- 16294114
TI  - Calibration of accelerometer output for adults.
AB  - This paper reviews the collective experience of monitor calibration studies in
      adults and seeks to answer the following questions: What has been done? What have
      we learned? What could be done to further enhance the comparability of results
      from future calibration research? Calibration studies in adults have typically
      used oxygen consumption as a criterion measure, similar types of source
      activities, and linear regression to obtain prediction equations that calibrate
      the activity counts to measured activity intensity levels. However, the
      methodological diversity of these studies has produced a great deal of variation
      in the resulting prediction equations and cut points, even when using the same
      monitor. Thus, data obtained from a relatively robust activity monitoring
      technology that captures many dynamic physical activities reasonably well have
      been splintered by the calibration process into a wide range of summary measures
      that are much less comparable than they could otherwise be. This heterogeneity in
      calibration results reduces our ability to interpret data obtained from
      accelerometers between different research groups, across the life span, between
      populations, and probably between the different monitor types. This report
      reviews and critiques methods typically used for developing calibration equations
      and determining activity count cut points for identifying specific intensities of
      PA among adults, and it highlights the need for flexible research methods that
      can enhance the comparability of results from future calibration studies.

PMID- 16294115
TI  - Calibration of accelerometer output for children.
AB  - Understanding the determinants of physical activity behavior in children and
      youths is essential to the design and implementation of intervention studies to
      increase physical activity. Objective methods to assess physical activity
      behavior using various types of motion detectors have been recommended as an
      alternative to self-report for this population because they are not subject to
      many of the sources of error associated with children's recall required for self
      report measures. This paper reviews the calibration of four different
      accelerometers used most frequently to assess physical activity and sedentary
      behavior in children. These accelerometers are the ActiGraph, Actical, Actiwatch,
      and the RT3 Triaxial Research Tracker. Studies are reviewed that describe the
      regression modeling approaches used to calibrate these devices using directly
      measured energy expenditure as the criterion. Point estimates of energy
      expenditure or count ranges corresponding to different activity intensities from
      several studies are presented. For a given accelerometer, the count cut points
      defining the boundaries for 3 and 6 METs vary substantially among the studies
      reviewed even though most studies include walking, running and free-living
      activities in the testing protocol. Alternative data processing using the raw
      acceleration signal is recommended as a possible alternative approach where the
      actual acceleration pattern is used to characterize activity behavior. Important
      considerations for defining best practices for accelerometer calibration in
      children and youths are presented.

PMID- 16294116
TI  - Conducting accelerometer-based activity assessments in field-based research.
AB  - PURPOSE: The purpose of this review is to address important methodological issues
      related to conducting accelerometer-based assessments of physical activity in
      free-living individuals. METHODS: We review the extant scientific literature for
      empirical information related to the following issues: product selection, number
      of accelerometers needed, placement of accelerometers, epoch length, and days of
      monitoring required to estimate habitual physical activity. We also discuss the
      various options related to distributing and collecting monitors and strategies to
      enhance compliance with the monitoring protocol. RESULTS: No definitive evidence
      exists currently to indicate that one make and model of accelerometer is more
      valid and reliable than another. Selection of accelerometer therefore remains
      primarily an issue of practicality, technical support, and comparability with
      other studies. Studies employing multiple accelerometers to estimate energy
      expenditure report only marginal improvements in explanatory power.
      Accelerometers are best placed on hip or the lower back. Although the issue of
      epoch length has not been studied in adults, the use of count cut points based on
      1-min time intervals maybe inappropriate in children and may result in
      underestimation of physical activity. Among adults, 3-5 d of monitoring is
      required to reliably estimate habitual physical activity. Among children and
      adolescents, the number of monitoring days required ranges from 4 to 9 d, making
      it difficult to draw a definitive conclusion for this population. Face-to-face
      distribution and collection of accelerometers is probably the best option in
      field-based research, but delivery and return by express carrier or registered
      mail is a viable option. CONCLUSION: Accelerometer-based activity assessments
      requires careful planning and the use of appropriate strategies to increase
      compliance.

PMID- 16294117
TI  - Accelerometer data reduction: a comparison of four reduction algorithms on select
      outcome variables.
AB  - PURPOSE: Accelerometers are recognized as a valid and objective tool to assess
      free-living physical activity. Despite the widespread use of accelerometers,
      there is no standardized way to process and summarize data from them, which
      limits our ability to compare results across studies. This paper a) reviews
      decision rules researchers have used in the past, b) compares the impact of using
      different decision rules on a common data set, and c) identifies issues to
      consider for accelerometer data reduction. METHODS: The methods sections of
      studies published in 2003 and 2004 were reviewed to determine what decision rules
      previous researchers have used to identify wearing period, minimal wear
      requirement for a valid day, spurious data, number of days used to calculate the
      outcome variables, and extract bouts of moderate to vigorous physical activity
      (MVPA). For this study, four data reduction algorithms that employ different
      decision rules were used to analyze the same data set. RESULTS: The review showed
      that among studies that reported their decision rules, much variability was
      observed. Overall, the analyses suggested that using different algorithms
      impacted several important outcome variables. The most stringent algorithm
      yielded significantly lower wearing time, the lowest activity counts per minute
      and counts per day, and fewer minutes of MVPA per day. An exploratory sensitivity
      analysis revealed that the most stringent inclusion criterion had an impact on
      sample size and wearing time, which in turn affected many outcome variables.
      CONCLUSIONS: These findings suggest that the decision rules employed to process
      accelerometer data have a significant impact on important outcome variables.
      Until guidelines are developed, it will remain difficult to compare findings
      across studies.

PMID- 16294118
TI  - Imputation of missing data when measuring physical activity by accelerometry.
AB  - PURPOSE: We consider the issue of summarizing accelerometer activity count data
      accumulated over multiple days when the time interval in which the monitor is
      worn is not uniform for every subject on every day. The fact that counts are not
      being recorded during periods in which the monitor is not worn means that many
      common estimators of daily physical activity are biased downward. METHODS: Data
      from the Trial for Activity in Adolescent Girls (TAAG), a multicenter group
      randomized trial to reduce the decline in physical activity among middle-school
      girls, were used to illustrate the problem of bias in estimation of physical
      activity due to missing accelerometer data. The effectiveness of two imputation
      procedures to reduce bias was investigated in a simulation experiment. Count data
      for an entire day, or a segment of the day were deleted at random or in an
      informative way with higher probability of missingness at upper levels of body
      mass index (BMI) and lower levels of physical activity. RESULTS: When data were
      deleted at random, estimates of activity computed from the observed data and
      those based on a data set in which the missing data have been imputed were
      equally unbiased; however, imputation estimates were more precise. When the data
      were deleted in a systematic fashion, the bias in estimated activity was lower
      using imputation procedures. Both imputation techniques, single imputation using
      the EM algorithm and multiple imputation (MI), performed similarly, with no
      significant differences in bias or precision. CONCLUSIONS: Researchers are
      encouraged to take advantage of software to implement missing value imputation,
      as estimates of activity are more precise and less biased in the presence of
      intermittent missing accelerometer data than those derived from an observed data
      analysis approach.

PMID- 16294119
TI  - Integration of physiological and accelerometer data to improve physical activity
      assessment.
AB  - PURPOSE: Accurate measurement of physical activity (PA) is a prerequisite to
      determine dose-response relationships between activity and health. The
      combination of HR and accelerometers (ACC) holds promise for improving the
      accuracy of PA assessment, but it is unclear how currently proposed modeling
      techniques compare and to what extent different levels of individual calibration
      (IC) of HR influence monitoring accuracy. METHODS: A total of 10 men and women
      (25.8 +/- 3.4 yr, 1.70 +/- 0.1 m, 71.7 +/- 11.8 kg, 24.4 +/- 5.0 kg.m-2) were
      recruited for this study, in which IC of HR to PA energy expenditure (PAEE)
      during both arm crank and treadmill activity were available. Participants
      completed 6 h of free-living activity, during which PAEE (obtained with indirect
      calorimetry), HR, hip ACC, arm ACC, and leg ACC were collected. PAEE was then
      modeled from two different methods of combining HR and ACC (arm-leg HR+M and
      branched model), both with IC and group-level calibration (GC) of HR, and also
      from hip ACC estimates alone. Estimates of PAEE were compared with criterion
      values for PAEE. RESULTS: Combined estimates of PAEE from the arm-leg HR+M and
      the branched model were similar when IC was used (R2 = 0.81, SEE = 0.55 METs and
      R2 = 0.75, SEE = 0.61 METs, respectively). When using GC, all estimates of PAEE
      had larger error, but the performance of the branched model suffered less than
      the arm-leg HR+M model (R2 = 0.75, SEE = 0.67 METs and R2 = 0.67, SEE = 0.88
      METs, respectively). Both combination modeling techniques were more precise than
      single-measure hip ACC estimates (R2 = 0.41, SEE = 0.96 METs). CONCLUSION: The
      combination of HR and ACC improves the accuracy of PAEE estimates and could be
      applied in large-scale epidemiological studies.

PMID- 16294120
TI  - Portable global positioning units to complement accelerometry-based physical
      activity monitors.
AB  - PURPOSE: This study examines the usefulness of complementing accelerometry-based
      physical activity measurement with spatial data from portable global positioning
      system (GPS) units to determine where physical activity occurs. METHODS: First,
      using the geographic distribution of data points and Bland-Altman plots, we
      examined GPS units' validity and interunit reliability by measuring the distance
      to a geodetic point. We also assessed interunit reliability by comparing GPS data
      collected in three built environment contexts. Second, we conducted a pilot study
      in which 35 participants wore GPS units and accelerometers in free-living
      conditions for 3 d. Moderate and vigorous physical activity (MVPA) bouts were
      matched to GPS data. We classified each bout as occurring inside or outside the
      participant's home neighborhood. Using unpaired t-tests and Fisher's exact tests,
      we compared neighborhood attributes for participants having the majority of MVPA
      bouts within their home neighborhood, relative to those with most bouts away from
      their home neighborhood. RESULTS: Average distance from each unit to the geodetic
      point was 3.02 m (SD 2.51). Average bias among units using Bland-Altman plots was
      0.90 m, ranging from -0.22 to 1.86 m, within the limits of agreement. For
      interunit reliability in the built environment contexts, the mean distance
      difference among units ranged between 10.7 m (SD 11.9) and 20.1 m (SD 21.8). For
      the pilot study involving participants, GPS data were available for 59.3% of all
      bouts (67% of MVPA time), of which 46% were in the participants' neighborhood.
      Participants obtaining most of their MVPA in their neighborhoods tend to live in
      areas with higher population density, housing unit density, street connectivity,
      and more public parks. CONCLUSION: Data recorded by portable GPS units is
      sufficiently precise to track participants' movements. Successful matching of
      activity monitor and locational data suggests GPS is a promising tool for
      complementing accelerometry-based physical activity measures. Our pilot analysis
      shows evidence that the relationship between environment and activity can be
      clarified by examining where physical activity occurs.

PMID- 16294121
TI  - Accelerometer use in physical activity: best practices and research
      recommendations.
AB  - Researchers are increasingly interested in the potential of accelerometers to
      improve our ability to measure and understand the health impacts of physical
      activity. Although accelerometers have been available commercially for more than
      25 yr, broad consensus about how to use these tools has not been established. At
      a scientific conference in December 2004, a number of scientists were invited to
      present papers, serve as reactors or moderators to papers, present posters of
      original research, or serve as members of an audience knowledgeable about the use
      of accelerometers. During 2 1/2 d, information about best practices of
      accelerometer use was presented and suggestions for future research were made.
      From the collective experience of papers presented and discussions held, five
      areas of accelerometer use were described. This paper summarizes the best
      practices and future research needs from those five areas: monitor selection,
      quality, and dependability; monitor use protocols; monitor calibration; analysis
      of accelerometer data; and integration with other data sources. Suggestions for
      reporting standards for journal articles also are presented.

PMID- 16294122
TI  - Management of supracondylar fractures of humerus with condylar involvement in
      children.
AB  - The intent of this study was to heighten awareness and to present the authors'
      experience of an uncommon supracondylar humerus fracture in children. Twenty-two
      children were studied over a period of 18 years. The average age was 7 years, and
      oldest child was 11 years at time of injury. The fracture subtypes with medial
      condyle, lateral condyle, and intercondylar extensions were classified based on
      radiographs. The patients were followed for an average of 6.5 years. Eighteen
      injuries (82%) were graded excellent or good, and there were two each with fair
      or poor outcomes. The most common complication was loss of carrying angle of more
      than 10 degrees, which occurred in three children. The best results were seen in
      cases where three or four cross-fixing wires were used across the fractures. The
      authors recommend closed reduction techniques and percutaneous multiple cross-pin
      fixation for the displaced fracture. The fracture is unique and distinctive
      enough to warrant a designation as supracondylar fracture type IV with subtypes
      in the younger child.

PMID- 16294124
TI  - Sagging rope sign in achondroplasia is different from Perthes disease.
AB  - The "sagging rope" sign is a radiopaque line seen on radiographs of hips with
      Perthes disease. The main purpose of this study was to determine the incidence,
      cause, and importance of this sign in achondroplasia and to reveal how it differs
      from in Perthes disease. Serial radiograms, along with two- and three-dimensional
      CT images were studied in 42 patients with achondroplasia. The sign was observed
      bilaterally in all patients. Evaluation of CT images revealed spherical heads
      with the presence of circumferential overhang in all hips. This circumferential
      overhang seen on three-dimensional CT images corresponded to the sagging rope
      sign on plain radiographs. The presence of the sagging rope sign in bilateral
      hips is a characteristic feature of achondroplasia. It usually appears before
      epiphyseal closure. Its cause, incidence, and nature differ from in Perthes
      disease, and its presence does not carry a negative prognosis in achondroplasia.

PMID- 16294123
TI  - Racial and economic disparity and the treatment of pediatric fractures.
AB  - Disparity in the treatment of various medical conditions in patient groups with
      differing racial and economic backgrounds has increasingly been reported. This
      paper examines the relationship between baseline racial and economic factors and
      the treatment of pediatric long-bone fractures. The 2000 Healthcare Cost and
      Utilization Project (HCUP) Kid's Inpatient Database (KID) was used to
      retrospectively examine the incidence and treatment of pediatric fractures. Data
      were included for supracondylar humerus (n = 2,957), femoral shaft (n = 1,726) or
      radius and ulna forearm fracture (n = 828) as their primary diagnosis were
      studied. Hispanic (78%) and black (82%) patients were more likely to receive
      closed reduction with internal fixation (percutaneous pinning) of supracondylar
      humerus fractures than whites (73%, P = 0.02). Despite a fairly large sample
      size, differences in treatment of supracondylar humerus fractures across primary
      payer or income groups were not statistically significant. Patients with femur
      fractures and private insurance were more likely to be treated with an external
      fixation device (7.2%) than patients in the Medicaid (3.8%) or self-pay (4.5%)
      groups (P = 0.015). No statistically significant difference was found in the
      treatment of forearm fractures across racial, primary payer or income groups.
      Racial and economic disparity is an important issue in medicine today. This study
      did demonstrate statistically significant differences in the treatment of
      pediatric supracondylar humerus across racial groups, with Blacks and Hispanics
      being more likely to receive percutaneous pinning of these injuries than Whites.
      Private insurance patients were also more likely to have femoral shaft fractures
      treated with an external fixator device than patients with Medicaid or self-pay
      as their primary payer. However, the clinical significance of these differences
      is not clear. Further research is needed to gain a more complete understanding of
      disparities in medicine, and their etiologies, in order to work towards
      optimizing the quality of medical care for all patient groups.

PMID- 16294126
TI  - Theoretical study of subluxation in early Legg-Calve-Perthes disease.
AB  - The relationship between mechanical subluxation and femoral head necrosis
      geometry in Legg-Calve-Perthes disease (LCP) was investigated with a three
      dimensional rigid body-spring method hip model. Femoral head models with
      progressively larger regions of necrosis, corresponding to the four Catterall
      grades, were placed in a spherical acetabular model and studied in static single
      limb stance configuration, with variable mechanical rigidity of the necrotic
      segment. The degree of subluxation was dependent on the geometric region of
      involvement, mechanical properties of the segment, and direction of loading
      force. In general, femoral head subluxation was always in the direction of the
      necrosis, modified by the anatomic and force environment. In the neutral
      position, the Catterall I models exhibited minimal subluxation. The Catterall II
      model subluxated anteriorly as collapse occurred, and the Catterall III model
      subluxated anteriorly and superiorly. Lateral subluxation could be produced by
      changing the loading force to a more vertical orientation. The Catterall IV model
      collapsed directly along the line of force application rather than subluxating.
      Reorientation of models with minor necrosis could improve stability, but
      reorientation of models with extensive necrosis had minimal effect on subluxation
      behavior. Higher-grade LCP involvement may lead to early subluxation,
      particularly anteriorly, which is difficult to visualize radiographically. The
      appearance of lateral subluxation may signal a change in the mechanical
      environment of the hip from clinical progression of the disease. Femoral head
      reorientation (osteotomy) may improve femoral head stability when necrosis is
      limited but is unlikely to reduce subluxation or collapse when extensive necrosis
      is present.

PMID- 16294125
TI  - Pubic symphyseal width in pediatric patients.
AB  - Traditionally, there has been no readily available and statistically sound method
      for evaluating the normal pubic symphyseal width in children. Normal values for
      the width of the pubic symphysis in the pediatric population are useful for
      determining pathologic widening, either congenital or posttraumatic. This
      investigation was directed at determining a reference range for the normal pubic
      symphyseal width according to age, age group, gender, and when combining these
      variables. Overall, the study found that the normal measurement for pediatric
      pubic symphyseal width ranges from 0.52 to 0.84 cm. The data also showed that the
      mean pubic symphyseal width for all variables combined was 0.68 cm (standard
      deviation of 0.16 cm and a 95% confidence interval of 0.668 to 0.690) and that
      anything greater than 0.84 cm needs further evaluation for pathology. The
      interclass correlation coefficient, test of interrater reliability, yielded
      moderate reliability of measurements between physicians.

PMID- 16294127
TI  - Stress fractures of the femoral diaphysis in children: a report of 5 cases and
      review of literature.
AB  - The authors report five new cases of the stress fracture of the femoral diaphysis
      in children. These injuries usually occurred without a history of recent increase
      of activity. Recently regained normal activity after long-term immobilization and
      a fibrous cortical defect were predisposing factors. The periosteal reactions
      were usually identified in the initial radiograph and were not confined to the
      medial cortex of the distal femur; they might occur in any part of the femoral
      diaphysis, and also concomitantly on the multiple cortex. The atypical
      radiographic presentations frequently required MRI for differential diagnosis.
      Even though the MRI may be confusing to the inexperienced observer, it can lead
      to the diagnosis of a stress fracture with confidence, negating the need for
      biopsy. Clinicians should be aware of this diagnostic entity in the differential
      diagnosis of femoral diaphyseal lesions in children because the occurrence might
      be more common than reported. Serial simple radiographic examinations taken at
      intervals to look for the evidence of progressive fracture healing and the
      restriction of activity or immobilization may be an adequate approach for
      management.

PMID- 16294128
TI  - Recurrence after femoral derotational osteotomy in cerebral palsy.
AB  - The authors studied the long-term results of femoral derotational osteotomy (FDO)
      for medial femoral torsion in ambulatory children with cerebral palsy. Thirty
      children with 45 femurs that underwent distal FDO were followed for a mean of 6.5
      years. Although correction was achieved after surgery, recurrence occurred during
      follow-up in 15 femurs. Preoperative mean external hip rotation of 10.7 +/- 7.2
      degrees increased to 41.3 +/- 16.6 degrees 1 year after surgery and decreased to
      28.2 +/- 14.7 degrees 5 years after surgery. On kinematic data, maximum hip
      rotation in stance of 30 degrees before surgery decreased to 8.7 degrees 1 year
      after surgery and increased to 16.1 degrees 5 years after surgery. Minimum hip
      rotation of 10.4 degrees before surgery was corrected to -4.3 degrees 1 year
      after surgery and was 0.8 degrees 5 years after surgery. Passive hip external
      rotation and kinematic hip rotation showed progressive deterioration of the
      initial correction. Patients having surgery prior to age 10 were more likely to
      show deterioration.

PMID- 16294130
TI  - Reliability and accuracy of MRI scanogram in the evaluation of limb length
      discrepancy.
AB  - The purpose of this study was to compare MRI scanogram with traditional
      radiographic methods for measurement of limb length. The authors hypothesized
      that MRI scanogram would be as reliable and accurate as radiographic scanogram in
      measurement of limb length without exposing patients to ionizing radiation.
      Twelve cadaveric femurs were measured using AP conventional radiographic
      scanogram, CT scanogram, MRI scanogram, and electronic caliper. Three
      orthopaedists performed two separate measurements using each technique.
      Intraobserver and interobserver variability was assessed for each of the three
      radiographic techniques. Accuracy was assessed by comparison of radiographic
      measurements to electronic caliper measurements of femur length. The reliability
      of all three radiographic limb length measurement techniques was excellent (ICC >
      0.99). The accuracy of plain radiographic scanogram was slightly superior to CT
      scanogram and MRI scanogram. The mean absolute differences for radiographic, CT,
      and MRI scanograms compared with the gold standard, direct caliper measurement,
      were 0.52 mm, 0.68 mm, and 2.90 mm, respectively. All three scanogram techniques
      showed excellent reliability and accuracy. Radiographic scanogram remains the
      gold standard for leg length measurement. MRI scanogram is slightly less accurate
      compared with radiographic scanogram, but it does not use ionizing radiation. MRI
      scanogram merits clinical study and comparison with the traditional radiographic
      scanogram method for measurement of limb length.

PMID- 16294129
TI  - Relationship between Body Mass Index and slipped capital femoral epiphysis.
AB  - Slipped capital femoral epiphysis (SCFE) is the most common hip disorder of
      adolescents and is known to be strongly associated with obesity. The use of Body
      Mass Index (BMI) as an assessment of obesity has been shown to be a very
      efficient technique. The Centers for Disease Control & Prevention has recently
      developed BMI-for-age percentile growth charts that have been shown to
      effectively evaluate obesity in the pediatric population. In the current study,
      the investigators provide a retrospective review, looking at the association
      between SCFE and obesity based on BMI. One hundred six subjects with
      radiographically diagnosed SCFE were compared with 46 controls without
      radiographic evidence of SCFE. In the SCFE group, 81.1% of individuals had a BMI
      above the 95th percentile; for the control group, the corresponding figure was
      only 41.3% (P < 0.0001). Multiple linear regression analysis controlling both for
      sex and age confirmed an equally significant difference (P < 0.0001) between SCFE
      patients and controls with regard to BMI. Based on pediatric obesity criteria
      designating a weight above the 95th percentile as obese and a weight between the
      85th and 95th percentile as "at risk" for obesity, clinicians can use BMI to
      define obesity, a highly modifiable risk factor for SCFE. Early intervention and
      lifestyle modifications may reduce the incidence of not only SCFE but other
      illnesses related to obesity as well.

PMID- 16294131
TI  - Pulsed low-intensity ultrasound: a new salvage procedure for delayed unions and
      nonunions after leg lengthening in children.
AB  - From 1998 to 2001, 112 lengthening procedures with or without deformity
      correction were performed in 108 children by external fixation with the Ilizarov
      method. Of these cases, 16.9% did not lead to a solid bone consolidation. Two
      children were operated the second time, mainly because of the parent's decision.
      Seventeen delayed unions or nonunions in 13 children were treated with low
      intensity pulsed ultrasound. All 17 cases healed within 3 to 12 months without
      any risk of surgical intervention.

PMID- 16294132
TI  - Use of free vascularized fibular graft for congenital ulnar pseudarthrosis:
      surgical decision making in the growing child.
AB  - Congenital pseudarthrosis of the ulna may cause growth disturbance and
      progressive forearm deformity, leading to functional compromise of the upper
      extremity. Treatment is challenging, and surgical decision making must take into
      account three goals of treatment: bony healing, distal radioulnar joint (DRUJ)
      stability, and continued skeletal growth. Four cases of congenital ulnar
      pseudarthrosis treated with free vascularized fibular graft are presented here.
      In two cases, the vascularized fibular graft included the proximal fibular
      epiphysis to reconstruct the DRUJ and ulnocarpal joints. Average age of the four
      patients at time of vascularized fibular grafting was 10 years (range 3-16
      years). Patients had undergone up to three previous failed operations. A step-cut
      osteotomy technique with rigid internal fixation was used in all patients. Donor
      site distal tibiofibular arthrodesis was performed in skeletally immature
      patients when appropriate. At average follow-up of 60 months (range 33-83
      months), all patients achieved bony union with full wrist range of motion
      compared with the contralateral extremity. The DRUJ was stable in all patients.
      Two skeletally immature patients with concomitant epiphyseal transfer showed
      continued skeletal growth. Two patients nearing skeletal maturity achieved
      revascularization of the distal ulna. Free vascularized fibular grafting is a
      successful option in the treatment of congenital ulnar pseudarthrosis.
      Reconstruction of the distal radioulnar and ulnocarpal joints using concomitant
      proximal fibular epiphyseal transfer should be considered in the skeletally
      immature patient with distal ulnar involvement.

PMID- 16294133
TI  - Effects of childhood obesity on three-dimensional knee joint biomechanics during
      walking.
AB  - Despite the increasing percentages of children who are overweight, few studies
      have investigated their gait patterns. The purpose of this study was to quantify
      the three-dimensional knee joint kinematics and kinetics during walking in
      children of varying body mass and to identify effects associated with obesity.
      Three-dimensional kinematics and kinetics were collected from children of normal
      weight and overweight during normal gait using surface-mounted infrared emitting
      diodes and a force plate. The overweight group walked with a significantly lower
      peak knee flexion angle during early stance, and no significant differences in
      peak internal knee extension moments were found between groups. However, the
      overweight group showed a significantly higher peak internal knee abduction
      moment during early stance. These data suggest that although overweight children
      may develop a gait adaptation to maintain a similar knee extensor load, they may
      not be able to compensate for alterations in the frontal plane, which may lead to
      increased medial compartment joint loads. Therefore, assuming that the
      development of varus angular deformities of the knee joint and, in the longer
      term, medial compartment osteoarthritis are influenced by cumulative stress, this
      study supports the understanding that childhood obesity may impart a greater risk
      for the development of these diseases.

PMID- 16294134
TI  - Quantitative segmental analysis of weight-bearing radiographs of the foot and
      ankle for children: normal alignment.
AB  - Clinical decision-making for the management of foot deformities in children is
      primarily based upon the analysis of weight-bearing radiographs of the foot and
      ankle. However, a comprehensive quantitative technique for the analysis of such
      radiographs has not been described. Ten radiographic measurements were developed
      and applied to the foot and ankle radiographs of a normal foot and ankle in 60
      children (mean age 10 years, range 5-17 years). Intraobserver variability and
      interobserver variability were determined for 10 cases. Mean values for the 10
      measurements were calculated from the entire study group. Intraobserver
      variability was excellent, with correlation coefficients for the 10 measurements
      ranging from 0.89 to 0.99. The absolute value of the mean differences in angular
      measurements ranged from 0.8 to 2.5 degrees. Interobserver variability was also
      excellent, with correlation coefficients ranging from 0.86 to 0.99. The absolute
      value of the mean differences in angular measurements ranged from 0.5 to 3.2
      degrees. The mean values, standard deviations, and ranges for the 10 radiographic
      parameters from the 60 normal feet have been determined. Clinically acceptable
      variability of 10 selected radiographic measurements of the foot and ankle was
      achieved, and normal values and ranges for these measurements were determined.
      Quantitative segmental analysis of foot and ankle alignment, using these 10
      radiographic measurements, can be used to describe common malalignment patterns,
      and this may assist in clinical decision-making and assessment of outcome.

PMID- 16294135
TI  - Calcaneocuboid fusion in children undergoing talectomy.
AB  - The aim of management of the child with a severe, rigid equinovarus foot is to
      provide a foot that is plantigrade and painless and can be placed within standard
      footwear. The authors identified a retrospective cohort of 17 children with a
      mean age at surgery of 5.6 years (range 2.3-9.6 years) who underwent 31 talectomy
      procedures for the management of their rigid, equinovarus foot deformities (14
      isolated talectomies, 17 combined talectomy and calcaneocuboid fusions). The
      underlying diagnosis was predominantly arthrogryposis. The average follow-up was
      9.7 years (range 2.3-9.5 years) and 3.8 years (range 2.8-9.6 years) respectively.
      The addition of calcaneocuboid fusion prevented the development of postoperative
      equinus, varus, adductus, and supination deformities as determined by clinical
      examination at medium-term follow-up (P = 0.01, P < 0.001, P < 0.001, P < 0.001,
      P < 0.01, respectively). This was associated with a decreased incidence of
      recurrent foot pain with weightbearing (P < 0.001) and a reduced need for
      revision surgery for pain or deformity (P < 0.001). This study determined that
      the addition of a concomitant calcaneocuboid fusion in the setting of talectomy
      may improve the medium-term surgical outcome.

PMID- 16294136
TI  - Calcaneal lengthening for the planovalgus foot deformity in children with
      cerebral palsy.
AB  - The authors studied the outcomes of calcaneal lengthening for the treatment of
      planovalgus foot deformity in ambulatory children with cerebral palsy (92 feet in
      56 children, mean age 9.2 years), attempting to define the surgical indication in
      terms of the severity of the foot deformity. Sixty-nine cases (75%) showed
      satisfactory clinical outcomes at an average follow-up of 5.2 years (range 4.0
      17.2 years). Gait parameters such as foot progression angle, ankle motion in
      sagittal plane, and its power generation improved after operation. Preoperative
      talocalcaneal angle, talo--first metatarsal angle, and calcaneal pitch on weight
      bearing lateral radiographs were predictive of the satisfactory results of the
      index operation. The authors conclude that calcaneal lengthening is an effective
      procedure for moderate to severe planovalgus foot deformities in children with
      cerebral palsy, but there is a limit under which the index operation can be
      performed safely: less than 35 degrees of talocalcaneal angle, less than 25
      degrees of talo--first metatarsal angle, and more than 5 degrees of calcaneal
      pitch on weight-bearing lateral radiographs.

PMID- 16294138
TI  - Assessment of health status in patients with cerebral palsy: what is the role of
      quality-of-life measures?
AB  - Measuring quality of life (QOL) in a population with a functional range as large
      as that of the pediatric cerebral palsy population is challenging. This study
      assessed the utility of two common QOL instruments in this population: the Child
      Health Questionnaire (CHQ) and the Pediatric Outcomes Data Collection Instrument
      (PODCI). The goal was to determine the efficacy of these questionnaires in
      detecting subtle differences in the QOL among children with cerebral palsy and to
      demonstrate the need for dynamic assessment when evaluating QOL within this
      group. There were 180 subjects between the ages of 5 and 18 years, split into
      three diagnostic groups-diplegic, hemiplegic, and quadriplegic. The PODCI was
      more sensitive to differences in the diplegic and hemiplegic groups, but
      quadriplegics exhibited a floor effect (50% or more scored at most 15 out of 100)
      in three of the five domains. The CHQ was more effective for the quadriplegic
      group, but the diplegic and hemiplegic diagnostic groups exhibited a ceiling
      effect on 2 of the 12 domains in that questionnaire. Because an instrument that
      uses dynamic assessment bases subsequent questions on the patient's response to
      the first ones, dynamic assessment would help to avoid ceiling and floor effects
      by asking questions more pertinent to the patient's actual condition, and it
      would save time that would have been wasted answering irrelevant questions about
      function and QOL.

PMID- 16294137
TI  - Impact of alendronate on quality of life in children with osteogenesis
      imperfecta.
AB  - Osteogenesis imperfecta (OI) is a debilitating clinical condition characterized
      by fragile bone and skeletal deformity. Over the past decade frequent reports
      have suggested that the cyclical administration of intravenous pamidronate has a
      positive impact on bone density and skeletal fractures; however, the impact of
      such therapy on the quality of life (QOL) has rarely been reported. Alendronate,
      an oral bisphosphonate, is widely used to treat osteoporosis. The purpose of this
      study was to evaluate the impact of daily alendronate on QOL and bone parameters
      in children with OI. A prospective double-blind crossover study was designed in
      which placebo was alternated with daily alendronate. Twenty children with types
      I, III, and IV OI were recruited. Seventeen patients completed the study. Markers
      of QOL were measured in children with type III and IV OI (n = 15) using total
      mobility (PEDI), self-care (WeeFIM), well-being, pain, and use of analgesic
      scores. After 1 year of alendronate therapy, vertebral bone mineral density (BMD)
      improved from a change in standard deviation score (z-score) of 0.89 +/- 0.19 to 
      0.12 +/- 0.14 after 1 year of placebo (P < 0.001). All QOL markers, except for
      mobility score, improved in response to alendronate therapy. Change in height z
      score also improved in response to 1 year of alendronate therapy (0.41 +/- 0.21
      vs. -0.09 +/- 0.11, P < 0.05). Alendronate therapy did not alter serum levels of
      calcium, osteocalcin, parathyroid hormone (PTH), 1, 5 (OH)2 vitamin D,
      cholesterol, or urinary hydroxyproline or any other biochemical marker evaluated.
      Alendronate decreased by 56% urinary cross-linked N-telopeptide of type 1
      collagen divided by urinary creatinine (uNTX/uCr). Daily alendronate therapy was
      well tolerated. Only two patients had mild gastrointestinal discomfort,
      responding to minor adjustments in alendronate intake. Daily alendronate therapy
      is safe and effective in improving QOL in children with OI.

PMID- 16294139
TI  - Biomechanics of olive wire positioning and tensioning characteristics.
AB  - The effect of the olive wire on the stiffness of external fixation has been
      studied previously, but there are limited data on the effect of the olive wire
      positioning and tensioning characteristics on the stiffness of external fixation.
      This study evaluated the influence of olive wire positioning (medially,
      laterally, posteriorly, and anteriorly) and tensioning characteristics
      (tensioning one end or both ends) on the stiffness of ring external fixation. A
      fiberglass composite tibia fixed into an idealized ring external frame was
      tested. All mechanical testing was performed with a servohydraulic test frame
      (MTS Bionix 858, Minneapolis, MN). Load-deformation behavior was compared among
      different wire design and olive wire positioning and tensioning characteristics
      under central axial compression, medial compression-bending, posterior
      compression-bending, posteromedial compression-bending, and torsion. The
      differences between tension values on opposite ends of the wire during different
      modalities of olive wire tensioning were also investigated. Olive wires tensioned
      on both ends provided significantly greater bending stiffness compared with
      smooth wires and olive wires tensioned only on the end opposite to the olive (P <
      0.05). There was a significant difference between the tension values on opposite
      ends of the olive wire during tensioning (P < 0.05). Tensioning both ends of the
      olive wires and positioning the olives on the side of bending significantly
      increase the bending stiffness of ring external fixation. This work provides a
      rationale for clinical decision-making about the use of tensioned olive wires
      opposed to smooth wires in ring external fixation.

PMID- 16294140
TI  - Percutaneous intramedullary decompression, curettage, and grafting with medical
      grade calcium sulfate pellets for unicameral bone cysts in children: a new
      minimally invasive technique.
AB  - Several treatment options exist for unicameral bone cysts (UBCs), including
      observation, steroid injection, bone marrow injection, and curettage and bone
      grafting. These are all associated with high recurrence rates, persistence, and
      occasional complications. Newer techniques have been described, most with
      variable success and only short follow-up reported. Because of these factors, a
      new minimally invasive percutaneous technique was developed for the treatment of
      UBCs in children. Twenty-eight children with UBCs who underwent percutaneous
      intramedullary decompression, curettage, and grafting with medical-grade calcium
      sulfate (MGCS) pellets by the senior author (J.P.D.) between April 2000 and April
      2003 were analyzed as part of a pediatric musculoskeletal tumor registry at a
      large tertiary children's hospital. Four patients were lost to follow-up, and the
      remaining 24 patients had an average follow-up of 21.9 months (range 4-48
      months). Twelve patients were followed for at least 24 months. Six of the 24
      children had received previous treatment of their UBC, most often at an outside
      institution. Follow-up was performed through clinical evaluation and radiographic
      review. Postoperative radiographs at most recent follow-up showed complete
      healing, defined as more than 95% opacification, in 22 of 24 patients (91.7%).
      One patient (4.2%) demonstrated partial healing, defined as 80% to 95%
      opacification. One patient had less than 80% radiographic healing (4.2%). All 24
      patients returned to full activities and were asymptomatic at most recent follow
      up. The only complication noted was a superficial suture abscess that occurred in
      one patient; this resolved with local treatment measures. The new minimally
      invasive technique of percutaneous intramedullary decompression, curettage, and
      grafting with MGCS pellets demonstrates favorable results with low complication
      and recurrence rates compared with conventional techniques. The role of
      intramedullary decompression as a part of this percutaneous technique is
      discussed.

PMID- 16294141
TI  - Congenital muscular torticollis in infants: ultrasound-assisted diagnosis and
      evaluation.
AB  - Ultrasonography is considered the modality of choice for differentiating
      congenital muscular torticollis from other pathologies in the neck. The authors
      present their experience with ultrasound examination for the evaluation and
      management of congenital muscular torticollis. Twenty-six infants, 14 boys and 12
      girls, age ranging from 1 to 16 weeks, with torticollis and a palpable mass were
      examined. Ultrasound showed a well-defined mass in the sternocleidomastoid
      muscle. The lesions ranged in size from 8 to 15.8 mm on maximal transverse
      diameter, with length ranging from 13.7 to 45.8 mm. Clinically the torticollis
      disappeared between 1 to 6 weeks, with complete clinical reduction of the
      palpated mass between 2 and 8.5 weeks. The ultrasonographic disappearance of the
      mass was delayed by an average of 2 weeks in comparison to the clinical
      disappearance of the mass. Ultrasound is advocated for the diagnosis and follow
      up of congenital muscular torticollis because it noninvasively provides reliable
      and dynamic information without sedation.

PMID- 16294142
TI  - Subsequent orthotic management of developmental dysplasia of the hip.

PMID- 16294143
TI  - [Pain and irritable bowel syndrome].

PMID- 16294145
TI  - Incidence of inflammatory bowel disease in the French West Indies (1997-1999).
AB  - OBJECTIVES: To investigate the incidence of inflammatory bowel disease in the
      French West Indies. METHODS: From January 1st 1997 to December 31st 1999 all
      patients observed with clinical symptoms suggestive of inflammatory bowel disease
      attending gastroenterologists practicing in Guadeloupe and Martinique were
      included. Patients were interviewed with a standard questionnaire to record data
      used by an expert to establish the final diagnosis of definite, probable or
      possible Crohn's disease, ulcerative colitis, unclassifiable chronic colitis or
      acute colitis, according to the EPIMAD registry. RESULTS: Sixty-six cases of
      ulcerative colitis (47.48%) including 12 cases of ulcerative proctitis (18.18% of
      the ulcerative colitis cohort), 55 of Crohn's disease (39.57%), 11 of
      unclassifiable chronic colitis (7.91%), and 7 of acute colitis (5.04%) were
      recorded. The crude annual incidence (per 100,000 inhabitants) based on definite
      and probable cases only was 2.44 for ulcerative colitis and 1.94 for Crohn's
      disease. The female/male ratio and median age at time of diagnosis were 1.61 and
      29 years for Crohn's disease and 1.46 and 34 years for ulcerative colitis
      respectively. The median time from symptom onset to diagnosis was 2 months for
      both diseases. CONCLUSIONS: The observed incidence of inflammatory bowel disease
      In the French West-Indies is lower than in metropolitan France. These data will
      serve as a basis to assess disease evolution.

PMID- 16294144
TI  - Digestive smooth muscle mitochondrial myopathy in patients with mitochondrial
      neuro-gastro-intestinal encephalomyopathy (MNGIE).
AB  - We report 3 new cases of Mitochondrial-Neuro-Gastro-Intestinal Encephalomyopathy
      (MNGIE) (or Pseudo-Obstruction-Leukoencephalopathy-Intestinal-Pseudoobstruction
      Syndrome [POLIP]), a rare disease that associates chronic intestinal pseudo
      obstruction (CIPO) and neurological symptoms. A review of the 72 reported cases
      together with these 3 cases revealed that this condition was associated with (a)
      a specific cluster of neurological symptoms including leukoencephalopathy (96%),
      polyneuropathy (96%), ophthalmoplegia (91%) and hearing loss (55%); (b) a CIPO
      syndrome with the presence of small bowel diverticulae (53%); and (c)
      mitochondrial cytopathy in 36 of the 37 tested patients (2 of our 3 cases), and
      thymidine phosphorylase gene mutations in all the 37 tested patients (2 of our
      cases). The etiology of POLIP/MNGIE syndrome appears therefore to be due to a
      mitochondrial cytopathy secondary to thymidine phosphorylase gene mutation(s). In
      3 cases, including 2 of our 3 patients, mitochondrial abnormalities were
      evidenced at the ultrastructural level in digestive smooth muscle demonstrating
      that the pathogenesis of gastrointestinal involvement was directly related to
      mitochondrial alterations in digestive smooth muscle cells.

PMID- 16294146
TI  - Palliative esophageal stent placement using endoscopic guidance without
      fluoroscopy.
AB  - AIMS: Fluoroscopy is not available in every endoscopic unit. This situation leads
      to delays in treatment or to transfer of patients to other centres for stent
      insertion. We assessed safety and effectiveness of expandable esophageal metal
      stent placement under endoscopic control without fluoroscopy using a thin
      gastroscope. PATIENTS AND METHODS: From October 2002 to June 2004, thirty-three
      consecutive patients have been included for esophageal stent placement under
      endoscopic control alone with a nasogastroscope (5.9 mm). A proximal release
      covered stent (Ultraflex; Boston Scientific Microvasive) was used. Indications
      were malignant esophageal stricture (N = 26), malignant extrinsic compression (N
      = 2 ) and esophago-respiratory neoplastic fistulae (N = 5). RESULTS: Stent
      placement using endoscopic control alone was successful in 30/33 (90%) patients.
      Complications occurred in 11 patients. Early complications (<7 days) included one
      death from pulmonary embolism, severe retrosternal pain needing transient
      morphinic treatment (N = 2) and GERD despite antisecretory therapy (N = 1). Late
      complications included: food impaction (N = 1), tumour overgrowth-related
      obstruction of the stent (N = 5) and one late esophago-respiratory fistula at 4
      months at the proximal end of the stent. Relief of dysphagia was obtained for all
      patients at 48 hours and dysphagia score decreased from 3.1 before stent to 1.2
      at 1 month (P < 0.05). CONCLUSION: Expandable esophageal stents can be accurately
      and safely placed using endoscopy with a thin gastrosocope. This method obviates
      the requirement of fluoroscopic access, lacking in many centres, and avoids
      exposure to X-ray.

PMID- 16294147
TI  - Endoscopic injection of botulinum toxin in the gastric antrum for the treatment
      of obesity. Results of a pilot study.
AB  - OBJECTIVES: The aim of this study was to observe the effects of endoscopic
      injections of botulinum toxin (BT) in the gastric antrum on body weight and
      gastric emptying in obese patients. PATIENTS AND METHODS: Obese patients were
      selected for the study. By endoscopy, 100 U of BT type A was injected into the
      prepyloric antral gastric wall. Before and after treatment body weight and solid
      gastric emptying were evaluated. RESULTS: Twelve patients were included into this
      study. Four and twelve weeks after the treatment median values of body weight and
      gastric emptying did not show significant changes compared to baseline values:
      body weight: (- 0.5 kg and - 1.0 kg respectively, P > 0.05) and gastric retention
      for solids at 90 min (+ 4.5% and +10.5% respectively, P > 0.05). Abnormal gastric
      emptying (solid gastric retention at 90 min > 50%) was observed in 22% of
      patients after 4 weeks and in 25% after 12 weeks. CONCLUSIONS: BT injected into
      the gastric antrum does not seem to significantly reduce body weight or delay
      gastric emptying in obese patients.

PMID- 16294148
TI  - Validation of the short-form REFLUX-QUAL (RQS), a gastro-esophageal reflux
      disease (GERD) specific quality of life questionnaire.
AB  - INTRODUCTION: Being an easy-to-use (eight items) quality of life questionnaire
      specific to GERD, the Reflux-Qual Short form (RQS) was developed for use in
      everyday practice. The purpose of this study was to assess the psychometric
      properties of the RQS. METHODS AND MATERIALS: The reliability of the RQS was
      measured by the Cronbach's alpha coefficient and its clinical validity by
      comparing the RQS score for increasing clinical severity groups. The RQS
      discriminative power was compared with that of the SF12. Sensitivity to change
      over time was measured by calculating effect-sizes. RESULTS: The reliability and
      validity of the questionnaire were assessed on a sample of 1195 patients. Its
      psychometric properties were very satisfactory: Cronbach alpha = 0.84; RQS score
      significantly reduced for the worst-affected patients; the discriminative power
      was up to 5 times higher when compared with the SF-12. Sensitivity to change over
      time, evaluated with 362 patients, showed highly significant differences between
      groups with different levels of clinical progression (P = 0.0001). CONCLUSION:
      The RQS is a quality of life measurement instrument specific to GERD which is
      short, reliable, valid, and sensitive to within and between-subject differences.

PMID- 16294150
TI  - [Sigmoid diverticulitis].

PMID- 16294149
TI  - Magnetic resonance imaging in Crohn's disease.
AB  - AIM: To evaluate the value of gadolinium enhanced MRI with oral opacification
      using a 5% mannitol solution (CE-Mannitol-MRI) to reveal bowel inflammation in
      pediatric patients with known or suspected Crohn's disease (CD). MATERIALS AND
      METHODS: Sixty-two consecutive children (median age 13.9 years) with known or
      suspected CD underwent ileocolonoscopy with biopsy, ultrasonography and CE
      Mannitol-MRI. CD activity was measured with the Pediatric Crohn's Disease
      Activity Index (PCDAI). Image quality, wall thickness, bowel wall enhancement and
      complications identified on CE-Mannitol-MRI were evaluated by two blinded
      radiologists. RESULTS: The sensitivity and specificity of CE-Mannitol-MRI for the
      diagnosis of CD were 83% and 100%, respectively. Bowel wall enhancement was
      higher in the group of patients with abnormal small bowel loops versus control
      group (P = 0.001). In patients with known CD, there was a positive correlation
      between wall thickness and PCDAI (P = 0.003). However, no significant correlation
      was demonstrated between parietal contrast enhancement and PCDAI (P = 0.497). CE
      Mannitol-MRI enabled identification of complications in 18 patients (9 fistulae,
      8 strictures and 1 intussusception). CONCLUSION: In pediatric patients with CD,
      CE-Mannitol-MRI contributes significantly to the identification of disease
      extension, severity and intestinal complications with adequate diagnostic
      accuracy. This technique could also be useful as the first line diagnostic
      exploration in young patients with suspected CD.

PMID- 16294152
TI  - [The gastrointestinal immune system and functional bowel disorders].

PMID- 16294151
TI  - [How to explore and treat a dyspeptic patient?].

PMID- 16294153
TI  - [Sphincter of Oddi dysfunction].

PMID- 16294154
TI  - [Sequelae of sub-mesocolic surgery].

PMID- 16294155
TI  - [When and how should a patient with a functional bowel disorder be referred to a
      psychotherapist?].

PMID- 16294156
TI  - [Chronic pseudo-obstruction of the intestine].

PMID- 16294158
TI  - [Cystic diseases of the liver. From embryology to malformations].
AB  - Cystic diseases of the liver which are in most cases hereditary, are related to
      an embryonic disorder know as ductal plate malformation. These diseases
      correspond to partial or total arrest of remodeling of the ductal plate, leading
      to more or less complete persistence of the excess of embryonic biliary
      structures. The ductal plate malformation may concern different segments of the
      intrahepatic biliary tree (segmental bile ducts, interlobular bile ducts and the
      smallest bile duct ramifications) leading to various pathoclinical entities.
      Caroli's disease is characterized by persistent dilated large intrahepatic bile
      ducts and appears to be the result of a factor acting during the early period of
      bile duct embryogenesis. Congenital hepatic fibrosis is characterized by ductal
      plate malformations of more distal, interlobular, bile ducts, and could be due to
      a factor that acts later on during bile duct development. This disorder may be
      isolated or associated with malformations of large, segmental, intrahepatic bile
      ducts. Von Meyenburg complexes and autosomal dominant polycystic liver disease
      are related to ductal plate malformation of more peripheral interlobular bile
      ducts and caused by a factor intervening in the later phase of bile duct
      embryogenesis. The genetic or non genetic factors leading to these ductal plate
      malformations are unknown.

PMID- 16294160
TI  - [Imaging in congenital fibrocystic diseases of the liver].
AB  - The identification of dilatations of the intrahepatic bile ducts in the absence
      of bile duct obstruction is rare. Imaging techniques, especially MR cholangio
      pancreaticography, generally permit the distinction between fibrocystic liver
      diseases and polycystic liver diseases. The presence of dilated sacciform or
      tubular bile ducts on cholangio-pancreaticography associated with a centrally
      located fibrovascular bundle (central dot sign) suggests Caroli's syndrome. The
      presence of associated signs of liver dysmorphia including right lobe atrophy and
      hypertrophy of segment IV suggests associated congenital hepatic fibrosis. The
      findings on cholangio-pancreaticography, computerized tomography or Doppler
      ultrasonography correlate well with the pathogenesis of fibrocystic liver
      diseases, linked to an embryologic malformation of the ductal plate.

PMID- 16294159
TI  - [Cystic liver diseases. Genetics and cell biology].
AB  - In 50% of cases, polycystic liver disease is associated with autosomal dominant
      polycystic kidney disease, which is caused by mutations in the PKD1 and PKD2
      genes that encode polycystin-1 and -2, respectively. These proteins form a
      polycystin-1/2 complex on the plasma membrane, including that localized on the
      surface of primary cilia, where they act as mechanosensors. Polycystin-1 acts as
      a (mechano)receptor of environmental signals, and polycystin-2 as a calcium
      channel mediating intracellular transduction. Isolated autosomal dominant
      polycystic liver disease is caused by mutations in PRKCSH that encodes
      hepatocystin, a protein of the endoplasmic reticulum, which may participate in
      the N-glycosylation and maturation of proteins addressed to the cell surface.
      Congenital hepatic fibrosis whether it is accompanied by bile duct dilatations
      (Caroli's syndrome) or not, may be associated with autosomal recessive polycystic
      kidney disease, which is caused by mutations in PKHD1 that encodes fibrocystin, a
      protein of primary cilia. Genetic defects in fibrocystin cause ciliary
      dysfunction, presently considered as a major pathogenic event in cystogenesis.
      Excessive cell proliferation, a hallmark of cystic biliary epithelium, occurs in
      combination with deregulation of the epidermal growth factor (EGF) and probably
      also estrogen receptors. EGF receptor antagonists inhibit kidney and liver cyst
      development in animal models, and are currently under investigation in phase I
      and II clinical trials in patients with autosomal dominant polycystic kidney
      disease.

PMID- 16294161
TI  - [Cystic diseases of the liver and biliary tract (except for hydatid cyst). Role
      of surgery].
AB  - The role of surgery in cystic diseases of the liver and biliary tract depends
      upon the kind of cysts. When they are symptomatic, solitary cysts of the liver
      may require laparoscopic unroofing. Mucinous cystadenoma should be resected since
      there is a risk of cystadenocarcinoma. Polycystic liver disease may require
      surgery when massive hepatomegaly results in pain or a worsening of the patient's
      general condition. Laparoscopic fenestration and partial hepatectomy are only
      indicated in a small number of selected patients with large or localized cysts.
      Orthotopic liver transplantation may be recommended in symptomatic cases with
      massive hepatomegaly even if there is no renal failure and no need for renal
      transplantation. Caroli's syndrome localized in one lobe or one segment should be
      resected since it leads to cholangiocarcinoma in more than 10% of cases. When
      cystic dilatations are diffuse, liver transplantation may be required.
      Choledochal cysts should be completely resected since cancer may arise in non
      resected parts. Complete resection may be associated with major hepatectomy.

PMID- 16294162
TI  - [Congenital cystic diseases of the intra and extrahepatic bile ducts].
AB  - Congenital cystic lesions of bile ducts may affect intra or extrahepatic bile
      ducts. Intrahepatic lesions include five entities: congenital hepatic fibrosis,
      Caroli's syndrome, von Meyenburg complexes, simple cyst of the liver and
      polycystic liver disease. Congenital hepatic fibrosis and von Meyenburg complexes
      are secondary to ductal plate malformation affecting the smallest intrahepatic
      bile ducts. Cystic dilatations are of small size and only detected at
      histological examination of the liver. They have few clinical consequences. In
      congenital hepatic fibrosis, the main manifestations result from portal
      hypertension. Caroli's syndrome is secondary to ductal plate malformation
      affecting the largest intrahepatic bile ducts. Cystic dilatations are macroscopic
      and responsible for cholangitis and may lead to biliary stones and carcinoma
      which develop within cystic dilatations. Caroli's syndrome may be or not
      associated with congenital hepatic fibrosis. In case of associated congenital
      hepatic fibrosis, portal hypertension is present. Simple cyst of the liver and
      polycystic liver disease are characterized by cystic dilatations which, by
      contrast to the preceding entities, do not communicate with the rest of biliary
      tree. As a result, they have only few clinical consequences. In congenital
      hepatic fibrosis and polycystic liver disease, renal abnormalities are frequently
      observed. They correspond to renal malformations associated with biliary
      malformations. In congenital hepatic fibrosis, renal lesions are characterized by
      ectatic collecting tubules which are present in two thirds of the cases and
      transmitted as an autosomal recessive trait. In polycystic liver disease, renal
      lesions are characterized by polycystic disease which is present in half of the
      cases and transmitted as an autosomal dominant trait. Congenital cystic lesions
      of extrahepatic bile ducts consist of choledochal cyst, which is secondary to
      malformation of the pancreato-biliary ductal junction. The major risk of
      choledochal cyst is the development of intracystic cancer, the prevention of
      which is total surgical resection of the cyst.

PMID- 16294164
TI  - [Eosinophilic gastroenteritis in a tropical area: report of a Congolese case].
AB  - Eosinophilic gastroenteritis is an uncommon disease with an unknown natural
      history, and its relation to digestive allergies has not been confirmed. This
      study reports the case of a 27 year old patient who developed eosinophilic
      gastroenteritis with gastric, intestinal, rectal and peritoneal localisations. In
      the Congo, massive blood hypereosinophilia suggests digestive parasitosis and
      gastroenteritis with malnutrition and cutaneous symptoms suggest AIDS/HIV, making
      the present agnosis uncommon.

PMID- 16294165
TI  - Endoscopic hemoclips in postoperative bleeding.
AB  - The field of application for endoscopic hemoclips has been increasingly extended,
      especially thanks to improvements in clips and additional clinical indications.
      Hemoclips are used more frequently for upper gastrointestinal (GI) bleeding and
      sometimes after therapeutic endoscopy. We report the successful use of endoscopic
      hemoclips in the management of two cases of postoperative colonic haemorrhage.

PMID- 16294166
TI  - [Radiation therapy with 131I-MIBG is still relevant for metastatic carcinoid
      tumors].
AB  - We report different treatment options (currently used and on trial) for a patient
      with a gastrointestinal carcinoid tumor and metastases in the liver, and discuss
      the advantages of using internal radiotherapy with 131I-MIBG rather than other
      treatments. According to the literature, this pathology has a poor prognosis, and
      considering the significant efficacy of this radiopharmaceutical treatment on
      symptoms, tumor reduction, and biochemical parameters, it seems to be under used.
      There are currently no standard treatment options. We present a management
      strategy for gastrointestinal carcinoid tumors with 131I-MIBG.

PMID- 16294167
TI  - New ambulatory treatment with radiofrequency for internal symptomatic
      hemorrhoids: morbidity evaluation.

PMID- 16294168
TI  - [Association of sigmoid adenocarcinoma and fibrous rectal stricture].

PMID- 16294169
TI  - [Peritonitis by sigmoid perforation in two patients with endometriosis: report of
      2 cases].

PMID- 16294172
TI  - [Understanding clinical trials in COPD].

PMID- 16294170
TI  - [Photodynamic therapy in gastroenterology].

PMID- 16294173
TI  - [Pulmonary arterial hypertension].

PMID- 16294174
TI  - [A plan for COPD! Why? How?].

PMID- 16294175
TI  - [Radon: an occupational and domestic carcinogen].

PMID- 16294176
TI  - [Subsaharan respiratory medicine--the case of Togo: poor relation in the
      Francophone family].

PMID- 16294177
TI  - [Results of FDG-PET scanning in the pre-operative staging of broncho-pulmonary
      tumors].
AB  - BACKGROUND: Positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG)
      has recently established itself as an important imaging strategy in the
      management of respectable non-small cell bronchial carcinoma (NSCLC). In this
      study we report our experience of the impact of FDG-PET in the pre-operative
      assessment of NSCLC. METHODS: In a single centre retrospective study between 01
      January 2000 and 31 Dec 2002, 108 FDGPET scans were performed during the
      preoperative assessment of histologically proven or strongly suspected NSCLC.
      RESULTS: The sensitivity, specificity and accuracy of FDG-PET for the
      characterization of a parenchymatous opacity were 96%, 71% and 92% respectively
      (4 false negatives, 5 false positives). The sensitivity, specificity and accuracy
      for mediastinal node involvement were 62%, 94% and 84% respectively (10 false
      negatives and 4 false positives). The sensitivity, specificity and accuracy for
      the characterization of adrenal nodules were 88%, 100% and 97% (1 false negative)
      and for satellite pulmonary nodules 50%, 75% and 64% (2 false negatives and 3
      false positives). CONCLUSION: FDG-PET is a useful imaging modality in the pre
      operative management of NSCLC but is limited particularly in the characterization
      of lesions less than 10 mm in diameter and in the evaluation of mediastinal lymph
      nodes.

PMID- 16294178
TI  - [Indoor radon exposure and lung cancer risk. Results of an epidemiological study
      carried out in France].
AB  - INTRODUCTION: Several epidemiological studies have indicated an increased risk of
      lung cancer associated with indoor radon exposure. As part of a large European
      project, a hospital based case-control study was carried out in four regions of
      France: Auvergne, Brittany, Languedoc-Roussillon and Limousin. MATERIAL AND
      METHODS: Individual data on demographic characteristics, residential history,
      smoking and occupational exposures were collected during face-to-face interviews.
      Radon concentrations were measured in each dwelling occupied by the subject
      during the 30-year period prior to the interview. RESULTS: 486 cases and 984
      controls were included in the study. After adjustment for age, sex, region,
      smoking history and occupational exposure, the risk of lung cancer increased by
      4% per 100 Bq/m(3), when considering cumulative exposure in the 30 years prior to
      diagnosis. CONCLUSION: The study indicates a positive association between lung
      cancer risk and indoor radon exposure. The risk estimate per unit of exposure is
      in agreement with other recently published indoor case-control studies.

PMID- 16294179
TI  - [Staphylococcus aureus: role and impact in the treatment of nosocomial
      pneumonia].
AB  - INTRODUCTION: Staphylococcus aureus (SA) has acquired a leading role in
      nosocomial pneumonia in terms of both frequency and severity, and poses
      therapeutic problems, namely antibiotic resistance and difficulties in the
      management of anti-staphylococcal drugs. STATE OF THE ART: Epidemiological data
      confirm that SA is implicated in almost a quarter nosocomial pneumonias, of which
      about a half are due to methicillin resistant SA (MRSA) in France. The
      pathophysiology of these infections most often involves inhalation following
      oropharyngeal carriage. In addition to the risk factors common to all nosocomial
      pneumonias there are the particular roles of head injury and coma, leading to an
      increased frequency of SA infection in neuro-surgical patients. PERSPECTIVES: The
      non-specific clinical picture, the grave prognosis of these pneumonias and the
      ineffectiveness against MRSA of the antibiotics used in the treatment of Gram
      negative infections make empirical treatment difficult. CONCLUSION: In addition
      to the antibiotics classically active against SA (notably methicillin for
      sensitive strains and glycopeptides for MRSA) new agents may allow improvement in
      the treatment of these patients, even if their place is not yet definitively
      established.

PMID- 16294180
TI  - [Dry powder inhalers in extreme clinical situations].
AB  - INTRODUCTION: Dry powder inhalers (DPIs) require a certain threshold of
      inspiratory effort to generate respirable particles. We undertook a literature
      review to determine whether this may, in particular clinical settings (young
      children, elderly subjects, acute or chronic respiratory obstructive syndromes -
      asthma and COPD), constitute a limitation on their use. STATE OF THE ART:
      Currently marketed DPIs exhibit different technical characteristics. Many factors
      may influence their efficacy, so that the predictive utility of in vitro tests is
      limited. Published clinical studies indicate that aerosol therapies inhaled with
      DPIs show clinical efficacy even at low inspiratory air flows in adults and
      children with acute asthma, in acute bronchoconstriction experimentally provoked
      by methacholine or histamine, in acute asthma attacks in adults and children, and
      in COPD-related airway obstruction. The efficacy of DPIs appears comparable to
      that of p-MDIs or nebulisation. However, the studies often have some limitations
      (including limited statistical power and patient selection) that may affect their
      value. PERSPECTIVES: The published studies analysed suggest that DPIs may be used
      in the great majority of clinical situations, subject to careful patient
      education. Nevertheless, p-MDIs with spacers remain recommended by international
      guidelines for children under the age of 6. CONCLUSIONS: Additional well-designed
      clinical studies remain desirable to establish firmly the efficacy of DPIs in
      these situations.

PMID- 16294181
TI  - [Domiciliary ventilation in patients with COPD].
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) has become one of the
      main indications for domiciliary ventilation, which is usually non-invasive
      (NIV). This review focuses on the pathophysiology processes and clinical trial
      data that underlie current guidelines from international societies. STATE OF THE
      ART: To date most published studies about domiciliary ventilation in COPD have
      been short-term and their message is complicated by the presence of significant
      methodological problems. The two controlled studies of > or =12 months-duration
      both found that survival was not improved by long-term NIV. Domiciliary
      ventilation may be considered when long-term oxygen therapy is unsuccessful and
      when failed with a progressive deterioration in clinical respiratory status with
      recurrent episodes of acute hypercapnic respiratory failure. A diurnal PaCO(2) >
      or =55 mmHg (7.3 kPa) is a necessary but not sufficient condition to consider
      domiciliary ventilation. CONCLUSION: Domiciliary ventilation should only be
      initiated in selected patients on the basis of clinical symptoms and exacerbation
      frequency. Until further characterization of patients who are likely to respond,
      the response to treatment should be assessed regularly.

PMID- 16294182
TI  - [The pre-operative assessment of bronchial carcinoma. The surgeon's viewpoint].
AB  - INTRODUCTION: The overall prognosis of non-small cell carcinoma of the bronchus
      (NSCLC) remains poor on account of frequently late diagnosis and associated co
      morbidity preventing the optimal treatment of the tumour. Surgical resection
      remains the best curative treatment for limited stage disease. STATE OF THE ART:
      The pre-operative assessment should determine whether the extent of the tumour
      permits complete resection and whether the physiological state of the patient
      would tolerate the curative resection required. The ultimate goal is to improve 5
      year survival. In the case of initial inoperability the assessment should
      determine whether pre-operative oncological treatment might make an advanced
      tumour operable (e.g. stage IIIA), or whether targeted medical treatment might
      improve the patient sufficiently to tolerate an intervention initially judged too
      risky. The rapid development of the technical modalities available for the
      assessment requires a continuous review of the current practice guidelines.
      Positron emission tomography has considerably augmented the accuracy of classical
      radiological assessment. Nevertheless staging by imaging alone remains imprecise
      to the extent that invasive examinations are still necessary to provide
      histological proof of the clinical stage of NSCLC. The techniques for assessing
      mediastinal invasion are developing rapidly and becoming more accurate and less
      invasive. Mediastinoscopy enhanced by modern video technology, ultrasound guided
      endoscopic biopsies and thoracoscopy are complimentary rather than competing
      techniques. The functional assessment should estimate the operative risk of the
      proposed pulmonary resection, identify the targeted actions aimed at reducing
      this risk or, in the absence of such actions, suggest less invasive but less well
      validated surgical techniques or even palliative treatments. When the operative
      risk cannot be reduced its precise estimation at least allows the patient to
      decide whether the risk seems acceptable in relation to the chances of a cure.
      VIEWPOINT AND CONCLUSIONS: In the future the pre-operative assessment of NSCLC
      should improve the detection of micro-metastases in order to optimise the choice
      of induction and adjuvant therapies. The increasing use of induction chemotherapy
      before surgical resection can only increase the importance of a detailed
      assessment for the selection of patients and the evaluation of results.

PMID- 16294183
TI  - [Pulmonary arterial hypertension].
AB  - INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare condition
      characterised by progressively elevated pulmonary arterial resistance leading to
      right heart failure. STATE OF THE ART: A recent classification distinguishes
      idiopathic PAH, familial PAH and PAH secondary to other conditions (connective
      tissue disease, congenital heart disease, portal hypertension, human
      immunodeficiency virus infection or appetite suppressant exposure).
      Echocardiography is the initial investigation of choice for non-invasive
      detection of PAH but measurement of pulmonary pressures and cardiac output during
      right-heart catheterization are necessary to confirm the diagnosis of PAH.
      Conventional treatment includes non-specific drugs (warfarin, diuretics, oxygen).
      Intravenous epoprostenol is the first-line treatment for the most severely
      affected patients. In less severe cases, the first-line treatment may include
      bosentan or a prostacyclin analogue. PERSPECTIVES AND CONCLUSIONS: Recent
      advances in the management of PAH have markedly improved prognosis. The avai
      lability of novel specific drugs including type 5 phosphodiesterase inhibitors
      offers novel therapeutic perspectives but their exact role in the treatment of
      PAH is still uncertain. The evolution of therapy from vasodilators to
      antiproliferative agents reflects the advancement in our understanding of the
      mechanisms mediating pulmonary arterial hypertension.

PMID- 16294184
TI  - [Rheumatoid arthritis and cystic fibrosis].
AB  - INTRODUCTION: Inflammatory arthropathies are rare complications of cystic
      fibrosis (CF). We describe three cases of rheumatoid arthritis (RA) occurring in
      patients with this disease. OBSERVATIONS: Among the 100 patients under the care
      of the adult CF centre in Lille 3 presented with RA. This developed at the ages
      of 17, 44 and 19 years with a FEV1 of 53%, 42% and 94% respectively. They were 2
      women and 1 man, with CFTR gene mutation delta F508 (1 homozygote and 2
      heterozygotes) and positive sweat tests. They were colonised with Staphylococcus
      aureus, and rheumatoid factor and/or anti CCP antibodies were positive. The
      appearance and progression of RA were associated with exacerbations of bronchial
      infection and deterioration of respiratory function. In 2 patients the RA was
      continuously progressive despite intensive treatment involving high dose cortico
      steroids, methotrexate (ineffective) followed by leflunomide (complicated by
      intractable respiratory infection). CONCLUSION: There is an increased incidence
      of RA in our patient population with CF. The new serum markers of RA including
      anti CCP are of diagnostic interest. The evolution of the two diseases is related
      and seems to be dependent on the level of infection leading to therapeutic
      problems.

PMID- 16294185
TI  - [Costo-vertebral collection complicating multifocal echinococcosis: surgical
      drainage via an anterior approach].
AB  - INTRODUCTION: Costo-vertebral echinoccoccus is a rare and serious condition which
      often presents with neurological complications requiring urgent surgical
      intervention. CASE REPORT: We report the case of a seven year old girl admitted
      with a clinical picture suggesting medullary compression secondary to multifocal
      Hydatid disease. As well as a costo-vertebral cyst with extension into the spinal
      canal, lesions were also seen in the lower lobe of her right lung and throughout
      the liver, confirmed by CT scan and by magnetic resonance imaging. A resection of
      Hydatid material as well as the posterior part of the 4th rib, the transverse
      process of the 4th costal vertebra and adjacent bone was carried out via a
      posterolateral thoracotomy. The cyst in the right lung was successfully excised
      at the same operation. Three months later six hepatic lesions were removed via a
      subcostal approach again without complication. A scan 23 months later revealed no
      evidence of residual hydatid disease. CONCLUSION: This case illustrates the
      pathophysiological features of costovertebral Hydatid disease and the advantages
      of an anterior surgical approach.

PMID- 16294186
TI  - [Pleural endometriosis: an unusual presentation].
AB  - INTRODUCTION: Numerous conditions can produce chronic exudative pleural
      effusions. Pleural endometriosis is a rare cause of unilateral effusion with
      diffuse pleural thickening. CLINICAL CASE: We report the case of chronic pleural
      effusion in a thirty year old African woman, where pleural endometriosis was
      diagnosed only following pleuro-pulmonary decortication, with the diagnosis being
      confirmed by immunohistochemistry. CONCLUSION: Pleural endometriosis must be
      considered as a possible diagnosis in women with pleural effusions of unknown
      aetiology. The presence of endometrial glands or of chorionic cells within the
      pleura is characteristic. Immunohistochemistry is an important diagnostic tool.

PMID- 16294187
TI  - [Visceral leishmaniasis and sarcoidosis].

PMID- 16294188
TI  - [Optimising speech during artificial ventilation].
AB  - Speech is an essential component of quality of life for patients treated with
      long term mechanical ventilation. Therefore trying to improve phonation should
      always sought by physicians treating these patients. We review the different
      tools and techniques available in order to restore speech for patients with home
      mechanical ventilation whether ventilation is done continuously or not.

PMID- 16294189
TI  - [Multivariate analysis].

PMID- 16294190
TI  - [Assessing respiratory muscle function in children].

PMID- 16294191
TI  - [Recommendations of the Francophone Society of Pneumology for pulmonary
      rehabilitation in COPD].

PMID- 16294193
TI  - Trial of modafinil for cocaine dependence.

PMID- 16294192
TI  - Defining exposure science.

PMID- 16294195
TI  - The future of dermatopathology.
AB  - Of the major issues that dermatopathology will face in the immediate future, two
      powerful challenges loom large. The first is the application of novel
      nondestructive imaging technologies to in vivo diagnosis in humans. The second is
      the application of molecular technologies to a diagnostic arena which formerly
      belonged exclusively to the light microscopist. The first to be considered in
      this context is the application of near infrared spectroscopy to the noninvasive
      in vivo diagnosis of neoplastic skin disease. The second will be a discussion of
      application, methodology and the current state of the art in microarray
      technologies as they apply to neoplastic dermatopathology and, in particular, the
      diagnosis and prognostication of melanoma.

PMID- 16294196
TI  - Immunohistochemistry for estrogen and progesterone receptors in the distinction
      of primary and metastatic mucinous tumors in the ovary: an analysis of 124 cases.
AB  - Estrogen (ER) and progesterone receptor (PR) expression in primary ovarian
      mucinous tumors and the utility of these markers for distinguishing metastatic
      mucinous carcinomas in the ovary from primary ovarian mucinous tumors have not
      been extensively investigated. Immunohistochemical studies were performed on 124
      mucinous tumors, including 52 primary ovarian tumors (30 atypical proliferative
      (borderline) mucinous tumors of gastrointestinal type, 11 atypical proliferative
      (borderline) mucinous tumors of seromucinous (endocervical-like) type, and 11
      invasive mucinous carcinomas of usual (gastrointestinal) type) and 72 metastatic
      mucinous carcinomas in the ovary (primary sites: colorectum (24), pancreas (13),
      endocervix (eight), stomach (four), gallbladder/bile duct (four), appendix
      (four), and unknown (15)). All atypical proliferative mucinous tumors of
      gastrointestinal type, primary ovarian mucinous carcinomas, and metastatic
      mucinous carcinomas were negative for ER and PR with the exception of three
      metastatic endocervical adenocarcinomas which exhibited only weak expression of
      ER without PR. All atypical proliferative mucinous tumors of seromucinous type
      expressed ER to some degree and seven had some expression of PR.
      Immunohistochemical assessment of hormone receptor expression is of no value in
      distinguishing the common types of primary ovarian mucinous tumors (atypical
      proliferative mucinous tumors of gastrointestinal type and mucinous carcinomas of
      usual type) from the vast majority of mucinous carcinomas metastatic to the
      ovary. The above observations on hormone receptor expression in primary ovarian
      mucinous tumors support the concept that atypical proliferative (borderline)
      mucinous tumors of gastrointestinal and seromucinous (endocervical-like) types
      are distinctive tumors.

PMID- 16294198
TI  - Vitreous haemorrhage following cardiopulmonary resuscitation.

PMID- 16294199
TI  - Moraxella as a cause of necrotizing fasciitis of the eyelid.

PMID- 16294197
TI  - Reprogramming liver-stem WB cells into functional insulin-producing cells by
      persistent expression of Pdx1- and Pdx1-VP16 mediated by lentiviral vectors.
AB  - Adenovirus-mediated transient expression of the pancreatic duodenal homeobox
      transcription factor Pdx1 in mouse liver activates pancreatic endocrine and
      exocrine genes, the latter reportedly resulting in severe hepatitis. Expression
      of a super-active form of Pdx1 or Pdx1-VP16 selectively transdifferentiates
      hepatic WB cells into functional pancreatic beta-like insulin-producing cells,
      without evidence of exocrine differentiation. No study has systematically
      compared the transdifferentiation efficiency of Pdx1 and Pdx1-VP16 at the
      cellular and molecular level. Comparisons can be ambiguous when vectors harboring
      a transcription factor cDNA have differing extents and duration of gene
      expression. In view of the remarkable capacity of lentiviral vector (LV) for
      delivering and integrating transgene into both dividing and nondividing cells, we
      transduced rat hepatic stem cell-like WB cells with LV-Pdx1 or LV-Pdx1-VP16, and
      then used the limiting-dilution technique to clone single-cell-derived cell lines
      that stably express either Pdx1 or Pdx1-VP16. With these cell lines, we studied:
      (a) the expression of Pdx1 or Pdx1-VP16 protein by Western blotting and
      immunocytochemistry; (b) the repertoire of long-term expression of Pdx1- or Pdx1
      VP16-induced pancreatic gene expression using RT-PCR methods; and (c) their
      capacity to serve as beta-cell surrogates in restoring euglycemia in
      streptozotocin-treated diabetic mice. We found that cell lines expressing either
      Pdx1 or Pdx1-VP16 long-term exhibited similar profiles for expression of genes
      related to pancreatic development and beta-cell function, and reversed
      hyperglycemia in diabetic mice. We also examined short-term expression of Pdx1 or
      Pdx1-VP16, and the results demonstrated that expression of Pdx1-VP16 is more
      efficient in initiating liver-to-endocrine pancreas transdifferentiation. Our
      findings demonstrate: (a) that the LV system is highly effective in producing
      persistent expression of Pdx1 or Pdx1-VP16 in WB hepatic cells; and (b) long
      term, persistent expression of either Pdx1 or Pdx1-VP16 is similarly effective in
      converting hepatic stem cells into pancreatic endocrine precursor cells that,
      upon transplantation into diabetic mice, become functional insulin-producing
      cells and restore euglycemia.

PMID- 16294200
TI  - Trypan blue-associated retinal toxicity post complicated cataract surgery.

PMID- 16294201
TI  - Protective ocular mechanisms in woodpeckers.
AB  - AIMS: Woodpeckers possess mechanisms protecting the eye from shaking/impact.
      Mechanisms available to woodpeckers but not humans may help explain some eye
      injuries in Shaken Baby syndrome (SBS). METHODS: Gross dissection and histologic
      examination of eyes and orbits of seven woodpeckers. RESULTS: All birds showed
      restricted axial globe movement due to the tight fit within the orbit and fascial
      connections between the orbital rim and sclera. The sclera was reinforced with
      cartilage and bone, the optic nerve lacked redundancy, and the vitreous lacked
      attachments to the posterior pole retina. CONCLUSIONS: Woodpecker eyes differ
      from human infants by an inability of the globe to move axially in the orbit, the
      sclera to deform, and the vitreous to shear the retina. These findings support
      current hypotheses that abusive acceleration-deceleration-induced ocular injury
      in human infants may be related to translation of vitreous within the globe and
      the globe within the orbit. The woodpecker presents a natural model resistant to
      mechanical forces that have some similarity to SBS.

PMID- 16294202
TI  - Changes in chromatic and achromatic contrast sensitivities following tropicamide
      administration.
AB  - PURPOSE: To investigate the effects of tropicamide on chromatic and achromatic
      contrast sensitivities over the physiological range of spatial frequencies.
      METHODS: A total of 26 healthy volunteers, with a mean age of 32 years, were
      examined with and without one drop of 1% tropicamide being administered 30 min
      previously. On each occasion, acuity and pupil diameter were recorded, and
      chromatic and achromatic contrast sensitivities were examined using the Sussex
      Grating Machine. RESULTS: Following tropicamide administration mean pupil
      diameter increased from 4.1 mm to 7.2 mm (P<0.001), and mean BCVA was reduced by
      0.07 LogMar units (P<0.001). Achromatic contrast sensitivity was significantly
      reduced following tropicamide administration at 2.20 cycles per degree (cpd)
      (P=0.01), 3.40 cpd (P=0.01), 10 cpd (P=0.04), 17 cpd (P=0.04), and 25 cpd
      (P<0.01). There was no difference in contrast sensitivity at lower spatial
      frequencies (0.33 and 0.66 cpd). Chromatic contrast sensitivity was not
      significantly altered when tested along the red-green and tritan confusion axes.
      CONCLUSIONS: Achromatic contrast sensitivity is significantly reduced following
      tropicamide administration at intermediate and high spatial frequencies. No
      significant changes were seen at low spatial frequencies and in chromatic
      contrast sensitivities.

PMID- 16294203
TI  - Decreased vision as the initial presenting symptom of disseminated prostatic
      disease.

PMID- 16294204
TI  - Comparison of ICG-assisted ILM peeling and triamcinolone-assisted posterior
      vitreous removal in diffuse diabetic macular oedema.
AB  - AIM: To compare the effect of indocyanine green (ICG)-assisted internal limiting
      membrane (ILM) peeling and triamcinolone acetonide-assisted posterior vitreous
      removal on visual acuity in patients with diffuse diabetic macular oedema (DMO).
      METHODS: In total, 24 patients with diffuse DMO who underwent pars plana
      vitrectomy were included in this study. In all, 11 patients (mean age 57 years)
      were performed ICG-assisted ILM peeling; while 13 patients (mean age 54 years)
      underwent triamcinolone-assisted posterior vitreous removal. Patients from two
      different treatment regimens were compared in terms of best-corrected visual
      acuity (BCVA) at postoperative sixth months. RESULTS: In ICG-assisted ILM peeling
      group, preoperative BCVA (1.3+/-0.4, mean+/-SD, logMAR) improved postoperatively
      to 0.9+/-0.5 (P=0.011). In eyes underwent triamcinolone-assisted posterior
      vitreous removal, baseline BCVA of 1.4+/-0.4 improved to 1.0+/-0.5 (P=0.007).
      There was no difference between baseline as well as postoperative sixth-month
      BCVA results of both groups (P=0.59 and P=0.57, respectively). CONCLUSIONS:
      Triamcinolone-assisted posterior vitreous removal and ICG-assisted ILM peeling
      have the same effect in terms of postoperative BCVA in patients with diffuse DMO.

PMID- 16294206
TI  - Intraoperative explantation of two single-piece hydrophobic acrylic intraocular
      lenses due to surface deposits.
AB  - PURPOSE: To report clinical, pathological, and laboratory analyses of two cases
      of single-piece hydrophobic acrylic intraocular lenses (IOLs), which presented
      with significant surface deposits during implantation. METHODS: The lenses were
      implanted with the manufacturer's recommended injector (loaded with Viscoat and
      Healon GV, respectively). Immediately after injection into the anterior chamber,
      areas on the lenses' surfaces were covered by deposits, which could not be
      entirely removed by irrigation/aspiration. The lenses were explanted and replaced
      with lenses of the same design. They underwent gross analyses, light microscopy,
      scanning electron microscopy, and energy dispersive X-ray spectroscopy for
      analysis of the elemental composition of the deposits. Liquid chromatography/mass
      spectroscopy was also performed to identify the presence of proteins. RESULTS:
      The deposits on the first lens had a granular appearance, forming a homogeneous
      layer mostly on the posterior lens surface. Larger crystal-like deposits were
      present mostly on the anterior surface of the second lens. Elemental analyses of
      the deposits in both cases revealed the presence of peaks of sodium, chloride,
      phosphate, and potassium, in addition to the peaks of carbon and oxygen (normal
      constituents of the lens material). Only protein components normally found in the
      anterior chamber during surgery, such as haemoglobin and albumin, were
      identified. CONCLUSIONS: The results obtained suggest that the deposits in both
      cases may have resulted from crystallization of the ophthalmic viscosurgical
      device normally used during the loading of the IOLs into the cartridges.

PMID- 16294207
TI  - Proton beam therapy for iris melanomas.
AB  - AIMS: To describe the results in terms of local control, eye preservation and
      systemic evolution of iris melanomas treated by proton beam irradiation. METHODS:
      Retrospective review of the charts of patients with iris melanoma treated by
      proton beam therapy between April 1998 and September 2002. Ciliary body melanomas
      with iris involvement or tumours with extrascleral invasion were excluded.
      Treatment consisted of 60 Gy of proton beam irradiation delivered in four
      fractions to the tumour volume. RESULTS: A total of 21 patients were treated,
      median follow-up of 33 months (8-72 months). 15 patients presented a lesion with
      documented growth. The median clinical diameter was 5 mm (2-8 mm), the median
      ultrasound diameter 4.8 mm (2-7.7 mm) The patients were 6% T1, 57.1% T2, and
      14.3% T3 all N0M0. The iridocorneal angle was invaded by the tumour in 71.4% of
      patients. At the end of follow-up, all patients were alive with no proven
      metastatic disease except one patient with suspicious liver lesions. None of the
      patients showed tumour progression or ocular relapse. The tumour response at 2
      years was a flat lesion for 6.3% of cases, partial regression in 75% and stable
      in 18.8%. None of the patients required secondary enucleation. The main
      complication was cataract (45% within 24 months of treatment). Raised intraocular
      pressure was observed in 15% of patients but no neovascular glaucoma.
      CONCLUSIONS: Proton beam therapy shows potential utility for selected cases of
      localised iris melanomas allowing excellent local tumour control and eye
      preservation. Further follow-up on larger series is needed to confirm these
      results.

PMID- 16294208
TI  - Exogenous Cushing's syndrome and topical ocular steroids.

PMID- 16294209
TI  - Matrix changes induced by transglutaminase 2 lead to inhibition of angiogenesis
      and tumor growth.
AB  - Administration of active TG2 to two different in vitro angiogenesis assays
      resulted in the accumulation of a complex extracellular matrix (ECM) leading to
      the suppression of endothelial tube formation without causing cell death. Matrix
      accumulation was accompanied by a decreased rate of ECM turnover, with increased
      resistance to matrix metalloproteinase-1. Intratumor injection of TG2 into mice
      bearing CT26 colon carcinoma tumors demonstrated a reduction in tumor growth, and
      in some cases tumor regression. In TG2 knockout mice, tumor progression was
      increased and survival rate reduced compared to wild-type mice. In wild-type
      mice, an increased presence of TG2 was detectable in the host tissue around the
      tumor. Analysis of CT26 tumors injected with TG2 revealed fibrotic-like tissue
      containing increased collagen, TG2-mediated crosslink and reduced organized
      vasculature. TG2-mediated modulation of cell behavior via changes in the ECM may
      provide a new approach to solid tumor therapy.

PMID- 16294210
TI  - Overexpression of the antiapoptotic protein A1 promotes the survival of double
      positive thymocytes awaiting positive selection.
AB  - As it has been shown for Mcl-1, Bcl-xl and Bcl-2, proteins of the Bcl-2 family
      play a crucial role during T-cell development in the thymus. We here show that
      the expression of the antiapoptotic gene A1 is specifically enhanced at the
      DN3/DN4 transition and in DP thymocytes that have been positively selected
      suggesting that A1 expression might be considered as a transcriptional signature
      of thymocytes that have received pre-TCR or TCR survival signal. Furthermore, we
      observed that A1-a overexpression in recombination activation gene 1-deficient
      mice transgenic for the major histocompatibillity complex class I-restricted F5
      TCR enhances cell survival of DP thymocytes and permits accumulation of DP cells
      awaiting positive selection. However, A1-a overexpression has no effect on
      negative selection. Therefore, our results suggest that A1 plays a specialized
      role in allowing survival of DP thymocytes and that its role can be distinguished
      from that of Mcl-1, Bcl-xl and Bcl-2.

PMID- 16294211
TI  - Activation of the transient receptor potential M2 channel and poly(ADP-ribose)
      polymerase is involved in oxidative stress-induced cardiomyocyte death.
AB  - Overproduction of reactive oxygen species is one of the major causes of cell
      death in ischemic-reperfusion (I/R) injury. In I/R animal models, electron
      microscopy (EM) has shown mixed apoptotic and necrotic characteristics in the
      same cardiomyocyte. The present study shows that H(2)O(2) activates both
      apoptotic and necrotic machineries in the same myocyte and that the
      ultrastructure seen using EM is very similar to that in I/R animal studies. The
      apoptotic component is caused by the activation of clotrimazole-sensitive,
      NAD(+)/ADP ribose/poly(ADP-ribose) polymerase (PARP)-dependent transient receptor
      potential M2 (TRPM2) channels, which induces mitochondrial [Na(+)](m) (and
      [Ca(2+)](m)) overload, resulting in mitochondrial membrane disruption, cytochrome
      c release, and caspase 3-dependent chromatin condensation/fragmentation. The
      necrotic component is caspase 3-independent and is caused by PARP-induced
      [ATP](i)/NAD(+) depletion, resulting in membrane permeabilization. Inhibition of
      either TRPM2 or PARP activity only partially inhibits cell death, while
      inhibition of both completely prevents the ultrastructural changes and myocyte
      death.

PMID- 16294212
TI  - Overexpression of Ets-1 in human hematopoietic progenitor cells blocks erythroid
      and promotes megakaryocytic differentiation.
AB  - Ets-1 is a widely expressed transcription factor implicated in development,
      tumorigenesis and hematopoiesis. We analyzed Ets-1 gene expression during human
      erythroid and megakaryocytic (MK) differentiation in unilineage cultures of CD34+
      progenitor cells. During erythroid maturation, Ets-1 is downmodulated and
      exported from the nucleus into the cytoplasm through an active mechanism mediated
      by a leucine-rich nuclear export signal. In contrast, during megakaryocytopoiesis
      Ets-1 increases and remains localized in the nucleus up to terminal maturation.
      Overexpression of Ets-1 in erythroid cells blocks maturation at the
      polychromatophilic stage, increases GATA-2 and decreases both GATA-1 and
      erythropoietin receptor expression. Conversely, Ets-1 overexpressing
      megakaryocytes are characterized by enhanced differentiation and maturation,
      coupled with upmodulation of GATA-2 and megakaryocyte-specific genes. We show
      that Ets-1 binds to and activates the GATA-2 promoter, in vitro and in vivo,
      indicating that one of the pathways through which Ets-1 blocks erythroid and
      promotes MK differentiation is via upmodulation of GATA-2 expression.

PMID- 16294213
TI  - Histological analyses of normally grown, fertile Apaf1-deficient mice.

PMID- 16294214
TI  - Evaluation of the role of caspase-6 in anticancer drug-induced apoptosis.

PMID- 16294215
TI  - Reduction of radiation-induced apoptosis by specific expression of Bcl-2 in
      normal cells.
AB  - Radiation-induced apoptosis is thought to underlie the toxicity of radiation to
      normal tissues as well as to cancer cells. We hypothesized that specific ectopic
      overexpression of the antiapoptotic molecule Bcl-2 in normal cells would inhibit
      radiation-induced apoptosis and thereby reduce radiation-induced toxicity in
      normal cells. To express Bcl-2 specifically in normal cells (which have wild-type
      (wt) p53) but not in cancer cells (which often have mutated p53), we constructed
      a Bcl-2 expression plasmid (PG13-Bcl-2) with a minimal promoter regulated by
      multiple wt p53 DNA-binding sites and found that the presence of wt p53 protein
      strongly upregulated Bcl-2 expression through this plasmid. Transfection of NIH
      3T3 fibroblasts, which express wt p53, with PG13-Bcl-2 increased cell survival
      and reduced apoptosis; however, transfection of MDA-MB-231 breast cancer cells,
      which have mutated p53, did not affect survival and apoptosis of those cells.
      These results indicate that irradiation of normal cells rapidly upregulates the
      expression of wt p53, which binds to the p53 binding sequence of the PG13-Bcl-2
      plasmid and increases the transcriptional activity of Bcl-2. Ectopic expression
      of Bcl-2 reduced radiation-induced apoptosis only in normal cells (not in cancer
      cells). Bcl-2 expression was detected in the lung from mice injected via a tail
      vein with LPD-PG13-Bcl-2 or LPD-CMV-Bcl-2, but did not in the lung from mice
      treated with DOTAP or LPD-PG13-mock. This novel approach to inhibiting radiation
      induced apoptosis in normal cells may allow such cells to be protected from
      radiation-induced toxicity. Further preclinical in vivo studies are needed.

PMID- 16294216
TI  - A role for Kaiso-p120ctn complexes in cancer?
AB  - Kaiso belongs to the zinc finger and broad-complex, tramtrack and bric-a
      brac/poxvirus and zinc finger (BTB/POZ) protein family that has been implicated
      in tumorigenesis. Kaiso was first discovered in a complex with the armadillo
      domain protein p120ctn and later shown to function as a transcriptional
      repressor. As p120ctn seems to relieve Kaiso-mediated repression, its altered
      intracellular localization in some cancer cells might result in aberrant Kaiso
      nuclear activity. Intriguingly, Kaiso's target genes include both methylated and
      sequence-specific recognition sites. The latter include genes that are modulated
      by the canonical Wnt (beta-catenin-T-cell factor) signalling pathway. Further
      interest in Kaiso stems from findings that its cytoplasmic versus nuclear
      localization is modulated by complex cues from the microenvironment.

PMID- 16294217
TI  - Recent progress in the battle between oncolytic viruses and tumours.
AB  - In the past 5 years, the field of oncolytic virus research has matured
      significantly and is moving past the stage of being a laboratory novelty into a
      new era of preclinical and clinical trials. What have recent anticancer trials of
      oncolytic viruses taught us about this exciting new line of therapeutics?

PMID- 16294218
TI  - Mechanisms of therapy-related carcinogenesis.
AB  - Therapy-related cancers, defined as second primary cancers that arise as a
      consequence of chemotherapy and/or radiotherapy, are unusual in that they have a
      well-defined aetiology. Knowledge of the specific nature of the initiating
      exposure and exactly when it occurred has made it easier to identify crucial
      genetic events and to model these in vitro and in vivo. As such, the study of
      therapy-related cancers has led to the elucidation of discrete mechanisms of
      carcinogenesis, including DNA double-strand-break-induced gene translocation and
      genomic instability conferred by loss of DNA repair. Unsurprisingly, some of
      these mechanisms seem to operate in the development of sporadic cancers.

PMID- 16294219
TI  - Hemolysis-associated endothelial dysfunction mediated by accelerated NO
      inactivation by decompartmentalized oxyhemoglobin.
AB  - During intravascular hemolysis in human disease, vasomotor tone and organ
      perfusion may be impaired by the increased reactivity of cell-free plasma
      hemoglobin (Hb) with NO. We experimentally produced acute intravascular hemolysis
      in a canine model in order to test the hypothesis that low levels of
      decompartmentalized or cell-free plasma Hb will severely reduce NO
      bioavailability and produce vasomotor instability. Importantly, in this model the
      total intravascular Hb level is unchanged; only the compartmentalization of Hb
      within the erythrocyte membrane is disrupted. Using a full-factorial design, we
      demonstrate that free water-induced intravascular hemolysis produces dose
      dependent systemic vasoconstriction and impairs renal function. We find that
      these physiologic changes are secondary to the stoichiometric oxidation of
      endogenous NO by cell-free plasma oxyhemoglobin. In this model, 80 ppm of inhaled
      NO gas oxidized 85-90% of plasma oxyhemoglobin to methemoglobin, thereby
      inhibiting endogenous NO scavenging by cell-free Hb. As a result, the
      vasoconstriction caused by acute hemolysis was attenuated and the responsiveness
      to systemically infused NO donors was restored. These observations confirm that
      the acute toxicity of intravascular hemolysis occurs secondarily to the
      accelerated dioxygenation reaction of plasma oxyhemoglobin with endothelium
      derived NO to form bioinactive nitrate. These biochemical and physiological
      studies demonstrate a major role for the intact erythrocyte in NO homeostasis and
      provide mechanistic support for the existence of a human syndrome of hemolysis
      associated NO dysregulation, which may contribute to the vasculopathy of
      hereditary, acquired, and iatrogenic hemolytic states.

PMID- 16294220
TI  - Pertussis toxin inhibits neutrophil recruitment to delay antibody-mediated
      clearance of Bordetella pertussis.
AB  - Whooping cough is considered a childhood disease, although there is growing
      evidence that children are infected by adult carriers. Additionally, increasing
      numbers of vaccinated adults are being diagnosed with Bordetella pertussis
      disease. Thus it is critical to understand how B. pertussis remains endemic even
      in highly vaccinated or immune populations. Here we used the mouse model to
      examine the nature of sterilizing immunity to B. pertussis. Antibodies were
      necessary to control infection but did not rapidly clear B. pertussis from the
      lungs. However, antibodies affected B. pertussis after a delay of at least a week
      by a mechanism that involved neutrophils and Fc receptors, suggesting that
      neutrophils phagocytose and clear antibody-opsonized bacteria via Fc receptors.
      B. pertussis blocked migration of neutrophils and inhibited their recruitment to
      the lungs during the first week of infection by a pertussis toxin-dependent (PTx
      dependent) mechanism; a PTx mutant of B. pertussis induced rapid neutrophil
      recruitment and was rapidly cleared from the lungs by adoptively transferred
      antibodies. Depletion of neutrophils abrogated the defects of the PTx mutant.
      Together these results indicate that PTx inhibits neutrophil recruitment, which
      consequently allows B. pertussis to avoid rapid antibody-mediated clearance and
      therefore successfully infect immune hosts.

PMID- 16294222
TI  - Timp3 deficiency in insulin receptor-haploinsufficient mice promotes diabetes and
      vascular inflammation via increased TNF-alpha.
AB  - Activation of inflammatory pathways may contribute to the beginning and the
      progression of both atherosclerosis and type 2 diabetes. Here we report a novel
      interaction between insulin action and control of inflammation, resulting in
      glucose intolerance and vascular inflammation and amenable to therapeutic
      modulation. In insulin receptor heterozygous (Insr+/-) mice, we identified the
      deficiency of tissue inhibitor of metalloproteinase 3 (Timp3, an inhibitor of
      both TNF-alpha-converting enzyme [TACE] and MMPs) as a common bond between
      glucose intolerance and vascular inflammation. Among Insr+/- mice, those that
      develop diabetes have reduced Timp3 and increased TACE activity. Unchecked TACE
      activity causes an increase in levels of soluble TNF-alpha, which subsequently
      promotes diabetes and vascular inflammation. Double heterozygous Insr+/-Timp3+/-
      mice develop mild hyperglycemia and hyperinsulinemia at 3 months and overt
      glucose intolerance and hyperinsulinemia at 6 months. A therapeutic role for
      Timp3/TACE modulation is supported by the observation that pharmacological
      inhibition of TACE led to marked reduction of hyperglycemia and vascular
      inflammation in Insr+/- diabetic mice, as well as by the observation of increased
      insulin sensitivity in Tace+/- mice compared with WT mice. Our results suggest
      that an interplay between reduced insulin action and unchecked TACE activity
      promotes diabetes and vascular inflammation.

PMID- 16294221
TI  - M-CSF mediates TNF-induced inflammatory osteolysis.
AB  - TNF-alpha is the dominant cytokine in inflammatory osteolysis. Using mice whose
      BM stromal cells and osteoclast precursors are chimeric for the presence of TNF
      receptors, we found that both cell types mediated the cytokine's osteoclastogenic
      properties. The greater contribution was made, however, by stromal cells that
      express the osteoclastogenic cytokine M-CSF. TNF-alpha stimulated M-CSF gene
      expression, in vivo, only in the presence of TNF-responsive stromal cells. M-CSF,
      in turn, induced the key osteoclastogenic cytokine receptor, receptor activator
      of NF-kappaB (RANK), in osteoclast precursors. In keeping with the
      proproliferative and survival properties of M-CSF, TNF-alpha enhanced osteoclast
      precursor number only in the presence of stromal cells bearing TNF receptors. To
      determine the clinical relevance of these observations, we induced inflammatory
      arthritis in wild-type mice and treated them with a mAb directed against the M
      CSF receptor, c-Fms. Anti-c-Fms mAb selectively and completely arrested the
      profound pathological osteoclastogenesis attending this condition, the
      significance of which is reflected by similar blunting of the in vivo bone
      resorption marker tartrate-resistant acid phosphatase 5b (TRACP 5b). Confirming
      that inhibition of the M-CSF signaling pathway targets TNF-alpha, anti-c-Fms also
      completely arrested osteolysis in TNF-injected mice with nominal effect on
      macrophage number. M-CSF and its receptor, c-Fms, therefore present as candidate
      therapeutic targets in states of inflammatory bone erosion.

PMID- 16294225
TI  - Ferreting out gas adsorption heats: the pseudo-isobaric method.
AB  - A new method is demonstrated for calculating gas adsorption heats from variable
      temperature infrared spectra of adsorbed molecules. By focusing on the low
      coverage regime, where (at equilibrium) there is only a very small fraction of
      molecules adsorbed, the procedure devised yields the corresponding value of
      adsorption enthalpy without needing to know the equilibrium pressure.
      Experimental measurements can thus be highly simplified, which constitutes one of
      the merits of the new method. Versatility for dealing with adsorption processes
      occurring at a low temperature, and having a small energy balance, is another
      favourable feature.

PMID- 16294223
TI  - Control of homeostatic proliferation by regulatory T cells.
AB  - Homeostatic proliferation of T cells leads to the generation of effector/memory
      cells, which have the potential to cause harm to the host. The role of Tregs in
      the control of homeostatic proliferation is unclear. In this study we utilized
      mice that either harbor or lack Tregs as recipients of monoclonal or polyclonal T
      cells. We observed that while Tregs completely prevented cell division of T cells
      displaying low affinity for self ligands, they had a less marked, albeit
      significant, effect on cell cycle entry of T cells displaying higher affinity.
      The presence of Tregs resulted in a lower accumulation of T cells, enhanced
      apoptosis, and impaired differentiation to a cytokine-producing state. We
      conclude that Tregs play a major role in the control of homeostatic
      proliferation.

PMID- 16294226
TI  - Enhancement of oxygen surface exchange kinetics of SrTiO(3) by alkaline earth
      metal oxides.
AB  - The oxygen incorporation reaction in undoped SrTiO(3) was investigated by
      electrical measurements (pressure modulation technique) in the temperature range
      from 650-920 degrees C and by means of tracer exchange experiments in the
      temperature range from 458-600 degrees C. The surface of the undoped SrTiO(3)
      single crystals was modified by alkaline earth metal compounds leading to a
      tremendous enhancement of the effective surface exchange rate for oxygen
      incorporation as compared to the uncoated surface.

PMID- 16294227
TI  - In situ spectroscopic investigation of heterogeneous catalysts and reaction media
      at high pressure.
AB  - In situ characterization of catalysts by means of complementary spectroscopic
      techniques can be regarded as the first step towards rational catalyst design.
      Spurred by the growing interest of catalytic reactions in supercritical fluids
      and by several industrial reactions traditionally performed at high pressure (>10
      bar), new demands and challenges are put to in situ spectroscopic
      characterization of heterogeneous catalytic reactions. In this article, we
      discuss the development and the use of spectroscopic and related techniques
      suitable for elucidating such high-pressure reactions. Selected examples from
      phase behaviour studies with a view cell, investigations with transmission and
      attenuated total reflection (ATR) infrared spectroscopy as well as X-ray
      absorption spectroscopy (EXAFS, XANES), are presented to show the strategies,
      opportunities and limitations of such high pressure in situ studies. Different
      facets appear to be important to gain insight into catalytic reactions in
      supercritical fluids: the identification of the phase behaviour of the reaction
      mixture, the behaviour of the fluid inside the porous catalyst, the processes
      occurring at the solid-fluid interface, the possible dissolution of active
      species and, similar as in gas-solid reactions, the establishment of structure
      activity relationships.

PMID- 16294224
TI  - Identification of thrombospondin 1 (TSP-1) as a novel mediator of cell injury in
      kidney ischemia.
AB  - Thrombospondin 1 (TSP-1) is a matricellular protein that inhibits angiogenesis
      and causes apoptosis in vivo and in vitro in several cancerous cells and tissues.
      Here we identify TSP-1 as the molecule with the highest induction level at 3
      hours of IR injury in rat and mouse kidneys subjected to ischemia/reperfusion
      (IR) injury using the DNA microarray approach. Northern hybridizations
      demonstrated that TSP-1 expression was undetectable at baseline, induced at 3 and
      12 hours, and returned to baseline levels at 48 hours of reperfusion.
      Immunocytochemical staining identified the injured proximal tubules as the
      predominant sites of expression of TSP-1 in IR injury and showed colocalization
      of TSP-1 with activated caspase-3. Addition of purified TSP-1 to normal kidney
      proximal tubule cells or cells subjected to ATP depletion in vitro induced injury
      as demonstrated by cytochrome c immunocytochemical staining and caspase-3
      activity. The deleterious role of TSP-1 in ischemic kidney injury was
      demonstrated directly in TSP-1 null mice, which showed significant protection
      against IR injury-induced renal failure and tubular damage. We propose that TSP-1
      is a novel regulator of ischemic damage in the kidney and may play an important
      role in the pathophysiology of ischemic kidney failure.

PMID- 16294228
TI  - On the statisticodynamical approach of final state distributions in simple bond
      fissions.
AB  - When the energy available to the products of a barrierless unimolecular reaction
      is of the order of 100 cm(-1), phase space theory leads usually to a good
      description of product state distributions. This is no longer the case for
      energies of the order of 1000 cm(-1). It seems, for example, that the excitation
      of the recoil energy distribution is underestimated by the theory as suggested by
      experimental results on the photodissociations of C(2)O and NCO. As an
      alternative, we propose a statisticodynamical approach of the previous processes
      based in part on transition state theory and in part on assumptions relative to
      the dynamics in the exit-channel. The recoil energy distributions obtained are
      now in good agreement with the measured ones, in spite of the simplicity of their
      mathematical expressions.

PMID- 16294229
TI  - Mesoporous palladium-the surface electrochemistry of palladium in aqueous sodium
      hydroxide and the cathodic reduction of nitrite.
AB  - The voltammetry of nanostructured palladium layers electrodeposited from a
      hexagonal liquid crystal phase onto platinum microdiscs show well defined peaks
      for the adsorption/desorption of hydrogen and surface oxidation/reduction in 2 M
      NaOH. These peaks are more clearly resolved than at smooth palladium and reveal
      the complications associated with hydrogen adsorption/desorption on palladium in
      aqueous alkaline solutions. The reduction of nitrite at the nanostructured
      palladium is also reported and it is shown that it occurs via a mechanism
      involving a chemical reaction between adsorbed hydrogen and adsorbed nitrite ion.

PMID- 16294230
TI  - Microwave activation of the electro-oxidation of glucose in alkaline media.
AB  - The oxidation of glucose is a complex process usually requiring catalytically
      active electrode surfaces or enzyme-modified electrodes. In this study the effect
      of high intensity microwave radiation on the oxidation of glucose in alkaline
      solution at Au, Cu, and Ni electrodes is reported. Calibration experiments with
      the Fe(CN)(6)(3-/4-) redox system in aqueous 0.1 M NaOH indicate that strong
      thermal effects occur at both 50 and 500 microm diameter electrodes with
      temperatures reaching 380 K. Extreme mass transport effects with mass transport
      coefficients of k(mt) > 0.01 m s(-1)(or k(mt) > 1.0 cm s(-1)) are observed at 50
      microm diameter electrodes in the presence of microwaves. The electrocatalytic
      oxidation of glucose at 500 microm diameter Au, Cu, or Ni electrodes immersed in
      0.1 M NaOH and in the presence of microwave radiation is shown to be dominated by
      kinetic control. The magnitude of glucose oxidation currents at Cu electrodes is
      shown to depend on the thickness of a pre-formed oxide layer. At 50 microm
      diameter Au, Cu, or Ni electrodes microwave enhanced current densities are
      generally higher, but only at Au electrodes is a significantly increased rate for
      the electrocatalytic oxidation of glucose to gluconolactone observed. This rate
      enhancement appears to be independent of temperature but microwave intensity
      dependent, and therefore non-thermal in nature. Voltammetric currents observed at
      Ni electrodes in the presence of microwaves show the best correlation with
      glucose concentration and are therefore analytically most useful.

PMID- 16294231
TI  - Formation of protonic defects in perovskite-type oxides with redox-active
      acceptors: case study on Fe-doped SrTiO(3).
AB  - The thermodynamics of water incorporation into Fe-doped SrTiO(3) was investigated
      by thermogravimetric measurements. Changes in valence states of redox-active
      dopant ions (Fe(3+)/Fe(4+)) with water vapor pressure were taken into account in
      the defect chemical analysis. The proton solubility was significantly enhanced by
      the presence of the redox centers. The hydration enthalpies and entropies were 
      60 kJ mol(-1) and -122 J mol(-1) K(-1). The defect chemical model was applied to
      describe the water vapor dependence of the electrical conductivity in mixed ionic
      and electronic conducting Fe-doped SrTiO(3) single crystals.

PMID- 16294232
TI  - Multiple isomers of uracil-water complexes: infrared spectroscopy in helium
      nanodroplets.
AB  - Infrared laser spectroscopy is used to show that four structural isomers of the
      uracil-water binary complex are formed in helium nanodroplets. The assignment of
      the infrared spectra is aided by measurements of vibrational transition moment
      angles (VTMAs) for various vibrational modes of these complexes. The experimental
      results are in excellent agreement with ab initio calculations, which had
      previously predicated the existence of the same four isomers. The results suggest
      that the relative abundances of the various isomers formed in helium droplets
      have more to do with the widths of the valleys in the potential surface that
      funnel into a particular local minimum than on the associated energetics.

PMID- 16294233
TI  - Mode-focusing in molecules by feedback-controlled shaping of femtosecond laser
      pulses.
AB  - The feasibility of mode-selective excitation with broadband femtosecond laser
      pulses is demonstrated for toluene in liquid phase. A learning-loop optimal
      control scheme was applied to a stimulated Raman excitation process.
      Modifications of the phase shape of one of the exciting pulses resulted in
      dramatic changes of the mode distribution reflected in coherent anti-Stokes Raman
      spectra. An evolutionary algorithm guided the coherent excitation process to a
      selective enhancement or suppression of one or more vibrational modes over the
      complete coherence lifetime spanning several picoseconds. New ways of spectral
      filtering as well as exciting possibilities of mode-selective studying of
      chemical reaction dynamics are indicated.

PMID- 16294234
TI  - Molecular dynamics simulation of uranyl(VI) adsorption equilibria onto an
      external montmorillonite surface.
AB  - We used molecular dynamics simulations to study the adsorption of aqueous uranyl
      species (UO(2)(2+)) onto clay mineral surfaces in the presence of sodium
      counterions and carbonato ligands. The large system size (10,000 atoms) and long
      simulation times (10 ns) allowed us to investigate the thermodynamics of ion
      adsorption, and the atomistic detail provided clues for the observed adsorption
      behavior. The model system consisted of the basal surface of a low-charge Na
      montmorillonite clay in contact with aqueous uranyl carbonate solutions with
      concentrations of 0.027 M, 0.081 M, and 0.162 M. Periodic boundary conditions
      were used in the simulations to better represent an aqueous solution interacting
      with an external clay surface. Uranyl adsorption tendency was found to decrease
      as the aqueous uranyl carbonate concentration was increased, while sodium
      adsorption remained constant. The observed behavior is explained by physical and
      chemical effects. As the ionic strength of the aqueous solution was increased,
      electrostatic factors prevented further uranyl adsorption once the surface charge
      had been neutralized. Additionally, the formation of aqueous uranyl carbonate
      complexes, including uranyl carbonato oligomers, contributed to the decreased
      uranyl adsorption tendency.

PMID- 16294235
TI  - Heterogeneous uptake and reactivity of formic acid on calcium carbonate
      particles: a Knudsen cell reactor, FTIR and SEM study.
AB  - The heterogeneous uptake and reactivity of formic acid (HCOOH), a common gas
      phase organic acid found in the environment, on calcium carbonate (CaCO(3))
      particles have been investigated using a Knudsen cell reactor, Fourier transform
      infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). FTIR
      measurements show that the adsorption of formic acid on the surface of calcium
      carbonate results in the formation of calcium formate. Besides calcium formate,
      carbonic acid is also a reaction product under dry conditions (<1% RH). Under dry
      conditions and at low pressures, the initial uptake coefficient of formic acid on
      CaCO(3) particles is measured to be 3 +/- 1 x 10(-3) and decreases as the surface
      saturates with adsorbed products. The maximum surface coverage of formic acid
      under dry conditions is determined to be (3 +/- 1)x 10(14) molecules cm(-2).
      Under humidified conditions (RH >10%), adsorbed water on the surface of the
      carbonate particles participates in the surface reactivity of these particles,
      which results in the enhanced uptake kinetics and extent of reaction of this
      organic acid on CaCO(3) as well as opens up several new reaction pathways. These
      reaction pathways include: (i) the water-assisted dissociation of carbonic acid
      to CO(2) and H(2)O and (ii) the formation of calcium formate islands and
      crystallites, as evident by SEM images. The results presented here show that
      adsorbed water plays a potentially important role in the surface chemistry of gas
      phase organic acids on calcium carbonate particles.

PMID- 16294236
TI  - Burial of gas-phase HNO(3) by growing ice surfaces under tropospheric conditions.
AB  - The uptake of gas-phase nitric acid by ice surfaces undergoing growth by vapor
      deposition has been performed for the first time under conditions of the free
      troposphere. The investigation was performed using a coated-wall flow tube
      coupled to a chemical ionization mass spectrometer, at nitric acid partial
      pressures between 10(-7) and 10(-6) hPa, at 214, 229 and 239 K. Ice surfaces were
      prepared as smooth ice films from ultra-pure water. During the experiments an
      excess flow of water vapor was added to the carrier gas flow and the existing ice
      surfaces grew by depositing water vapor. The average growth rates ranged from 0.7
      5 microm min(-1), values similar to those which prevail in some portions of the
      atmosphere. With growing ice the long term uptake of nitric acid is significantly
      enhanced compared to an experiment performed at equilibrium, i.e. at 100%
      relative humidity (RH) with respect to ice. The fraction of HNO(3) that is
      deposited onto the growing ice surface is independent of the growth rate and may
      be driven by the solubility of the nitric acid in the growing ice film rather
      than by condensation kinetics alone.

PMID- 16294237
TI  - Monte Carlo simulation of segregation in ceramic thin films.
AB  - A Monte Carlo exchange technique is used to study segregation in thin ceramic
      films with application to MgO/MnO. The approach is not restricted to the dilute
      limit. Surface concentrations as a function of temperature and film composition
      are determined directly from the simulations. For all compositions studied
      (Mn(chi)Mg(1-chi)O, 0 < or = chi < or = 1) the (001) surface is Mn(2+) rich; the
      occupancy of sites by Mn(2+) decreases rapidly with depth. The ratio of the
      number of Mn(2+) to Mg(2+) ions at the surface decreases as a function of
      temperature. The calculated enthalpies of segregation of Mn(2+) for the thin film
      are strongly dependent on the total Mn(2+) concentration at small Mn(2+)
      concentrations, with the enthalpy of segregation varying by a factor of two with
      surface coverage.

PMID- 16294238
TI  - Unusual aggregates from the oxidation of alkene self-assembled monolayers: a
      previously unrecognized mechanism for SAM ozonolysis?
AB  - Self-assembled monolayers (SAMs) of vinyl-terminated 3- and 8-carbon compounds
      were generated on Si substrates and reacted at room temperature with
      approximately 1 ppm gaseous O(3). A combination of atomic force microscopy (AFM),
      scanning electron microscopy (SEM), Auger electron spectroscopy (AES) and time-of
      flight secondary ion mass spectrometry (TOF-SIMS) was used to study the surface
      composition and morphology after oxidation. A distribution of large (
      approximately 0.1-10 microm) organic aggregates was formed, while the surrounding
      substrate became depleted of carbon compared to the unreacted SAM. This highly
      unusual result establishes that the mechanism of ozonolysis of alkene SAMs must
      have a channel that is unique compared to that in the gas phase or in solution,
      and may involve polymerization induced by the Criegee intermediate (CI).
      Oxidation at 60% RH led to the formation of a number of smaller aggregates,
      suggesting water intercepted the CI in competition with aggregate formation. The
      uptake of water, measured using transmission FTIR, was not increased upon
      oxidation of these films. In conjunction with literature reports of polymer
      formation from VOC-NO(x) photooxidations, these results suggest that formation of
      aggregates and polymers in the atmosphere is much more widespread than previously
      thought. The implications for the ozonolysis of alkenes on surfaces, for the
      transformation of organics in the atmosphere, and for the reactions and stability
      of unsaturated SAMs, are discussed.

PMID- 16294239
TI  - SERS studies of the adsorption of guanine derivatives on gold colloidal
      nanoparticles.
AB  - Surface enhanced Raman scattering spectra of guanine, guanosine and 2'
      deoxyguanosine adsorbed on gold colloidal nanoparticles were obtained. From the
      striking similarity of the SERS spectra of these compounds, it can be evidenced
      that guanosine and 2'-deoxyguanosine adsorb on gold nanoparticles through the
      guanine moiety. The molecular sites involved in the interaction with the gold
      surface are the same for the 3 compounds: the oxygen of the carbonilic group and
      the N(7) atom. Guanine, guanosine and 2'-deoxyguanosine adsorb on the gold
      substrates with a tilted orientation with respect to the metal surface. SERS data
      were interpreted taking into account density functional theoretical (DFT)
      calculations of guanine.

PMID- 16294240
TI  - Gold-polyaniline composite. Part I. Moving electrochemical interface.
AB  - The controlled growth of gold nanoclusters in polyaniline is predicated by the
      ability of PANI to switch from conducting to insulating form and by the fact that
      imine nitrogens form a strong complex with chloroaurate anions. The principal
      technique used in this study has been chronopotentiometric stripping. The
      chronopotentiograms indicate that the electrochemical interface for the
      Pt/Au/polyaniline/electrolyte shifts back and forth from the solution/PANI
      interface to Au/PANI interface. By adjusting experimental conditions the size and
      the size distribution of Au clusters can be controlled.

PMID- 16294241
TI  - Gold-polyaniline composites. Part II. Effects of nanometer sized particles.
AB  - The amount of electronic charge transferred between gold particles and
      polyaniline depends not only on the electron affinity of the two materials but
      also on the size of the gold particles. As measured by X-ray photoelectron
      spectroscopy, for particles < approximately 5 nm the binding energy of the
      electrons is size dependent. This "nano-effect" has its origin in the
      electrostatics of particles. It is demonstrated as a measurable shift of the
      binding energy of the Au(4f7/2) photoelectrons emitted from Au particles embedded
      in a polyaniline matrix. Gold nanoparticle size was evaluated by high resolution
      transmission electron microscopy.

PMID- 16294242
TI  - Corannulene and corazulene tiling of nanostructures.
AB  - Tiling modification in nanostructure modeling can be achieved by map operations,
      as well as the well-known Stone-Wales bond rotation. In this respect, sequences
      of classical operations, or single generalized operations, were used to obtain
      corannulenic flowers and corannulene-like azulenic patterns. The first
      "corazulenic" tessellation is reported. The aromaticity of some cages tessellated
      by the above supra-faces is discussed in terms of several different criteria. The
      covering was given as a pi-electron partition within some Kekule valence
      structures.The well-known geometric index of aromaticity HOMA (harmonic
      oscillator model of aromaticity) enabled the evaluation of local aromaticity of
      the discussed supra-faces and brought evidence for several dominant Kekule
      valence structures. The most intriguing is the "Kekule-Dewar" valence structure
      of the cage C(192) having a disjoint corazulenic tessellation.

PMID- 16294243
TI  - Frequency-selective response of periodically forced coupled FHN models via system
      size multi-resonance.
AB  - We consider system of globally coupled FitzHugh-Nagumo (FHN) models; each element
      is subjected to a subthreshold periodic signal and independent Gaussian white
      noise. With the variation of the system size, the spike train of the mean field
      of the system fires according to the period of the subthreshold external signal
      or to the interior time scale of the FHN model. The influence of the coupling
      strength is also investigated. It only influences the response of the mean field
      to external signal. If two external signals are injected to the system
      simultaneously, the least-common-multiple periods or other common multiples may
      be selected by different system sizes.

PMID- 16294244
TI  - Asymmetric hydrogenation of aromatic compounds.
AB  - The asymmetric hydrogenation of aromatic and heteroaromatic compounds arguably
      presents one of the most attractive methods for the synthesis of six-membered
      cyclic compounds. In recent years, a number of promising stereoselective methods
      for the asymmetric hydrogenation of pyridines and related heterocycles have been
      reported.

PMID- 16294245
TI  - Catalytic and enantioselective allylic C-H activation with donor-acceptor
      substituted carbenoids.
AB  - In this perspective we give an overview of enantioselective C-H activation at
      allylic sites by means of rhodium(II)-stabilized donor-acceptor-substituted
      carbenoids. This methodology has been proven to be both an equivalent to
      established asymmetric reaction sequences and a new synthetic approach with no
      established counterpart in organic synthesis.

PMID- 16294246
TI  - Dramatic effect of N-substituents in viologens on single electron transfer from
      tributylphosphine.
AB  - A single electron transfer (SET) takes place from tributylphosphine (1a) to 1
      alkyl-1'-methylviologens in acetonitrile containing a large amount of methanol
      under an argon atmosphere. In contrast, no SET takes place from 1a to viologens
      whose alkyl groups on the nitrogens are larger than the methyl group under the
      same conditions, 1a instead nucleophilically attacking the viologen to form a
      covalent adduct. This dramatic substituent effect is discussed in terms of SET
      occurring within a tight encounter complex formed between the phosphine and the
      viologen.

PMID- 16294247
TI  - NMR studies of interactions between periplasmic chaperones from uropathogenic E.
      coli and pilicides that interfere with chaperone function and pilus assembly.
AB  - Adherence of uropathogenic Escherichia coli to host tissue is mediated by pili,
      which are hair-like protein structures extending from the outer cell membrane of
      the bacterium. The chaperones FimC and PapD are key components in pilus assembly
      since they catalyse folding of subunits that are incorporated in type 1 and P
      pili, respectively, and also transport the subunits across the periplasmic space.
      Recently, compounds that inhibit pilus biogenesis and interfere with chaperone
      subunit interactions have been discovered and termed pilicides. In this paper NMR
      spectroscopy was used to study the interaction of different pilicides with PapD
      and FimC in order to gain structural knowledge that would explain the effect that
      some pilicides have on pilus assembly. First relaxation-edited NMR experiments
      revealed that the pilicides bound to the PapD chaperone with mM affinity. Then
      the pilicide-chaperone interaction surface was investigated through chemical
      shift mapping using 15N-labelled FimC. Principal component analysis performed on
      the chemical shift perturbation data revealed the presence of three binding sites
      on the surface of FimC, which interacted with three different classes of
      pilicides. Analysis of structure-activity relationships suggested that pilicides
      reduce pilus assembly in E. coli either by binding in the cleft of the chaperone,
      or by influencing the orientation of the flexible F1-G1 loop, both of which are
      part of the surface by which the chaperone forms complexes with pilus subunits.
      It is suggested that binding to either of these sites interferes with folding of
      the pilus subunits, which occurs during formation of the chaperone-subunit
      complexes. In addition, pilicides that influence the F1-G1 loop also appear to
      reduce pilus formation by their ability to dissociate chaperone-subunit
      complexes.

PMID- 16294248
TI  - Tetrakis(imidazolium) macrocyclic receptors for anion binding.
AB  - New (tetrakis)imidazolium macrocyclic receptor systems of variable cavity size
      have been synthesised by stepwise alkylation reactions of bis(imidazolium)
      precursor compounds. Proton NMR titration studies reveal the macrocycles to
      strongly bind halide and benzoate anions, with two receptor systems displaying
      notable selectivity for fluoride in competitive acetonitrile-water (9:1) solvent
      media.

PMID- 16294249
TI  - Design, synthesis and evaluation of graftable thrombin inhibitors for the
      preparation of blood-compatible polymer materials.
AB  - Piperazinyl-amide derivatives of N-alpha-(3-trifluoromethyl-benzenesulfonyl)-L
      arginine (1) were synthesized as graftable thrombin inhibitors. The possible
      disturbance of biological activity due to a variable spacer-arm fixed on the N-4
      piperazinyl position was evaluated in vitro, against human alpha-thrombin, and in
      blood coagulation assay. Molecular modelling (in silico analysis) and X-ray
      diffraction studies of thrombin-inhibitor complexes were also performed. The
      fixation of bioactive molecules on poly(butylene terephthalate) (PBT) and
      poly(ethylene terephthalate) (PET) membranes was performed by wet chemistry
      treatment and evaluated by XPS analysis. Surface grafting of inhibitor 1d
      improved the membrane hemocompatibility by reducing blood clot formation on the
      modified surface.

PMID- 16294250
TI  - Stabilization of tandem dG-dA base pairs in DNA-hairpins: replacement of the
      canonical bases by 7-deaza-7-propynylpurines.
AB  - The stabilizing effect of 7-propynylated 7-deazapurine nucleosides on DNA
      hairpins and DNA-duplexes containing d(GA) mismatches was investigated. The
      corresponding oligonucleotides were synthesized using solid-phase synthesis. For
      this purpose, the phosphoramidite of 7-deaza-7-propynyl-2'-deoxyadenosine (3c)
      was prepared. The incorporation of 3c instead of dA into the tandem d(GA) base
      pair of a DNA-hairpin alters the secondary structure, but has a positive effect
      on the duplex stability. A complete replacement of the canonical nucleosides of
      the tandem d(GA) base pair by 3c and 7-deaza-7-propynyl-2'-deoxyguanosine results
      in a significant base pair stabilization.

PMID- 16294251
TI  - Copper(II)-mediated resolution of alpha-halo carboxylic acids with chiral O,O'
      dibenzoyltartaric acid: spontaneous racemization and crystallization-induced
      dynamic resolution.
AB  - Herein we present a new example of coordination-mediated resolution of racemic
      acids by a chiral acid. The reaction of copper(II) acetate monohydrate, optically
      pure O,O'-dibenzoyltartaric acid (DBTA) and racemic alpha-bromo-2
      chlorophenylacetic acid (HL1) in acetonitrile solution afforded a binuclear
      copper(II) complex with D-DBTA dianion, alpha-bromo-2-chlorophenylacetate and
      acetate as ligands. After decomposition of the complex with acid, the optically
      active acid ((R)-HL1) was obtained. Similarly, alpha-bromo-2-fluorophenylacetic
      acid (HL2), alpha-bromo-2-bromophenylacetic acid (HL3), alpha-chloro-2
      chlorophenylacetic acid (HL4), alpha-chloro-2-fluorophenylacetic acid (HL5),
      alpha-bromophenylacetic acid (HL6), alpha-bromo-4-chlorophenylacetic acid (HL7),
      2-bromopropionic acid (HL8) and 2-chloropropionic acid (HL9) were resolved by the
      same method. Satisfactory results were obtained for HL2 to HL5. For HL6 and HL7,
      only racemic acids were obtained. For the two alpha-halo aliphatic acids (HL8 and
      HL9), poor enantioselectivity was obtained. It is more interesting that three
      acids (HL1, HL2 and HL3) could spontaneously racemize in acetonitrile solution,
      which resulted in crystallization-induced dynamic resolution (CIDR) with greater
      than 50% yield.

PMID- 16294252
TI  - Concise synthesis of aryl-C-nucleosides by Friedel-Crafts alkylation.
AB  - A fast and simplified synthesis of 1',2'-dideoxy-1'-pyrenyl-riboside and several
      other C-nucleosides is shown. Shelf-stable 1-O-methyl-3,5-di-O-toluoyl-2
      deoxyribose is demonstrated to serve as a versatile glycosyl donor in Lewis acid
      promoted Friedel-Crafts alkylations of unsubstituted pyrene and other inexpensive
      arenes such as fluorene and methylnaphthalene. The reaction conditions favour the
      formation of beta-configurated C-nucleosides which renders additional
      epimerisation steps unnecessary. As a result, protected beta-aryl-C-nucleosides
      are available directly from non-substituted arenes in three steps overall.

PMID- 16294253
TI  - Acetylenic cyclodextrins for multireceptor architectures: cups with sticky ends
      for the formation of extension wires and junctions.
AB  - A mono-6-O-propargyl permethylated beta-cyclodextrin, 3, has been prepared by two
      synthetic routes as a versatile building block for the construction of
      cyclodextrin dimers and trimers with a core junction which is potentially
      electron conducting. Glaser-Hay coupling of 3 gave beta-cyclodextrin dimer 6, and
      Pd(0)-catalysed coupling allowed the preparation of a cyclodextrin dimer with a
      1,4-phenylene bridge, 7, and a cyclodextrin trimer based on a 1,3,5
      trisubstituted benzene, 8. All compounds have been fully characterised, and in
      particular, detailed analysis by 2D NMR spectroscopic techniques has provided
      useful insight into the identities of the compounds. The detailed full
      characterisation of mono-3,6-anhydro-heptakis(2,3-O-methyl)-hexakis(6-O-methyl)
      beta-cyclodextrin, 5, is also described. Product 5 is formed during the
      methylation of compound 3, and its formation was found to be sensitive to the
      reaction conditions. The absorption and fluorescence spectra of the phenylene
      bridged dimer 7 and trimer 8 are also reported. They show different properties of
      the excited state based on the different electronic coupling imposed by the
      phenylene core.

PMID- 16294254
TI  - On the reaction of diphenylketene with isocyanides.
AB  - The products obtained from the reaction of diphenylketene with a variety of
      isocyanides are shown to depend heavily on the concentration of diphenylketene; a
      high concentration results in the precedented dioxolane derivatives, at much
      lower concentrations the reactions follow an alternative course and polycyclic
      beta-lactams are generated by a cascade of formal pericyclic reactions.

PMID- 16294255
TI  - Synthesis and biological evaluation of mannose-6-phosphate-coated multivalent
      dendritic cluster glycosides.
AB  - The synthesis of multivalent dendritic cluster glycosides of mannopyranosyl-6
      phosphate is presented. Poly(amido amine)-based dendrimers of 0.5-3.5
      generations, containing carboxylic acid peripheral functionalities, were utilized
      so as to install 4, 8, 16 and 32 mannopyranosyl-6-phosphate residues at the
      peripheries of the dendrimers. Amide bond formation between an amine-tethered
      mannopyranosyl-6-phosphate monomer unit and carboxylic acid-functionalized
      dendrimers was conducted to synthesize the dendritic cluster glycosides. The
      constitutions of the Man-6-P-containing dendrimers were assessed by 1H, 13C and
      31P NMR spectroscopies and the sugar content analysis by a resorcinol assay.
      Preliminary biological studies with few newly synthesized Man-6-P-containing
      dendrimers showed that these compounds could bind the purified goat liver mannose
      6-phosphate receptor (MPR 300) protein.

PMID- 16294256
TI  - Synthesis of 1,5-diisopropyl substituted 6-oxoverdazyls.
AB  - 1,5-Diisopropyl-6-oxo-verdazyl free radicals were synthesized via the
      condensation of BOC protected isopropyl hydrazine with phosgene, deprotection
      with aqueous HCl, condensation with aldehydes to form tetrazanes and finally
      oxidation to give the free radicals. The introduction of isopropyl groups results
      in free radicals that show greater solubility in a variety of solvents and are
      more stable than their methyl substituted counterparts. ESR shows reduced
      hyperfine coupling to the isopropyl methine hydrogens consistent with this
      hydrogen being in the plane of the verdazyl ring.

PMID- 16294257
TI  - Skeleton-selective fluorescent chemosensor based on cyclodextrin bearing a 4
      amino-7-nitrobenz-2-oxa-1,3-diazole moiety.
AB  - A new type of fluorescent chemosensor, based on modified cyclodextrins bearing
      the fluorophore unit NBD-amine, was prepared. One of these new chemosensors,
      NC0betaCD, is sensitive to adamantane and borneol derivatives, which have a
      comparatively spherical shape that fits the beta-CD cavity, but is not sensitive
      to bile acids, which are strongly bound by the native beta-CD. Even in the
      presence of a bile acid, NC0betaCD can detect 1-adamantanol. Another of this new
      type of chemosensors, NC0gammaCD, is sensitive to bile acids but not to
      adamantane derivatives. The response of the new type of chemosensors to a guest
      was an increase in the fluorescence intensity.

PMID- 16294258
TI  - Synthesis of nitrogen and sulfur macrocycles with cis exogenous oxygen and sulfur
      donor atoms.
AB  - A series of new N4 and N8 macrocycles has been prepared, that includes cis
      exogenous O2, S2 and S/O atoms to allow chelation to a metal external to the
      macrocyclic ring. We found that thioamide units within the macrocycles were
      unstable to attack by secondary amines and thus alkylated precursors containing
      only tertiary amines could lead to exogenous-S2 macrocycles. Cyclisation of
      alkylated tetraamine precursors with dimethyloxalate or dithiooxamide led to both
      N4 and N8 macrocycles via 1 + 1 and 2 + 2 cyclisation reactions with exogenous-O2
      or S2 respectively. Alkylation of preformed exogenous-O2 macrocycles was explored
      and led to alkyl substitution at the secondary amine nitrogens in the ring,
      however synthesis of these species was overall lower yielding than cyclisation
      using alkylated tetraamine precursors. Thionation of an exo-O2 macrocycle using
      an analogue of Lawesson's Reagent led to formation of the analogous exogenous-S2
      and exogenous-O,S macrocycles. Related S2N2 macrocycles with exogenous-O2 were
      prepared by a cyclisation route but could not be isolated free of larger ring
      analogues.

PMID- 16294259
TI  - Synthetic studies of pseurotin A: preparation of an advanced lactam aldehyde
      intermediate.
AB  - An efficient synthesis of the lactam core of pseurotin A has been accomplished.
      Key features of this synthesis include a tandem oxidation-cyclization to form the
      lactam from an acetylenic amide precursor. Although coupling of a lactam aldehyde
      with an appropriate side chain was not effective, it is anticipated that
      incorporating a partial side chain at an earlier stage should permit completion
      of the total synthesis of pseurotin A.

PMID- 16294260
TI  - The state of pediatric bone: summary of the ASBMR pediatric bone initiative.

PMID- 16294261
TI  - Social position affects bone mass in childhood through opposing actions on height
      and weight.
AB  - We studied relationships between social position of the mother in pregnancy and
      bone mass of the child at age 9.9 years. The tendency for social position to
      increase bone area and bone mass through a positive influence on height was
      opposed by a negative effect of social position on weight and fat mass.
      INTRODUCTION: Evidence that social factors influence skeletal growth raises the
      possibility that bone mass acquisition in childhood is socially determined.
      MATERIALS AND METHODS: To clarify the role of social factors in bone mass
      acquisition in childhood, we studied relationships between these variables in the
      Avon Longitudinal Study of Parents and Children (ALSPAC). Measures of the
      mother's social position during pregnancy were linked to DXA results obtained at
      age 9.9 years in 6,702 children. Linear regression analyses were carried out
      after adjusting for age and gender. Because social position may affect height and
      weight of the child, analyses were repeated after adjusting for these additional
      variables. RESULTS: Measures of social position in pregnancy were unrelated to
      total body BMC in analyses adjusted for age and gender alone. However, after
      adjusting for height, which was positively related to social position, a strong
      negative association was observed between BMC and housing tenure (p < 0.001),
      maternal education (p < 0.001), paternal education (p < 0.001), and social class
      (p < 0.001). Similar results were obtained for bone area. After adjusting for
      weight as well as height, an association between social position and BMC and bone
      area was no longer observed. Hence, social position seems to exert opposing
      height- and weight-dependent effects on BMC and bone area in childhood. In
      further analyses, we found that adjusting for fat mass of the child led to
      similar results to those obtained with weight. CONCLUSIONS: Social position in
      childhood seems to be positively related to bone mass acquisition in childhood as
      a consequence of enhanced gain in height (i.e., longitudinal growth). However,
      this influence is counteracted by the tendency for increased fat deposition in
      those from a lower social position to increase bone area, presumably reflecting
      the stimulation of appositional bone growth.

PMID- 16294262
TI  - Bone and body composition of children and adolescents with repeated forearm
      fractures.
AB  - DXA measurements in 90 children and adolescents with repeated forearm fractures
      showed reduced ultradistal radius BMC and BMD values and elevated adiposity,
      suggesting site-specific bone weakness and high body weight increase fracture
      risk. Symptoms to cow milk, low calcium intakes, early age of first fracture, and
      overweight were over-represented in the sample. INTRODUCTION: Although many
      apparently healthy children fracture their forearms repeatedly during growth, no
      previous studies of their bone health and body composition have been undertaken.
      Nor has the prevalence of established risk factors for fracture in such a
      population been assessed. MATERIALS AND METHODS: Ninety children and adolescents
      (47 girls and 43 boys) 5-19 years of age, who had experienced at least two
      fractures of the forearm, were studied. Bone size and mineralization were
      assessed using DXA at the ultradistal radius, one-third radius, neck of femur,
      hip trochanter, lumbar spine, and total body. Total body lean mass and fat mass
      were also determined. The prevalence of six risk factors for fracture were also
      examined, and their influence on ultradistal BMC Z scores was assessed. RESULTS:
      Participants experienced 295 fractures (74.9% forearm). Children with an early
      age of first fracture had higher rates of fracture per l00 years of exposure than
      those fracturing later. Four risk factors for fracture were over-represented in
      observed versus expected percentages: early age of first fracture (27.7% versus
      11.3%), adverse symptoms to cow milk (22.2% versus 6.7%), low dietary calcium
      intake (20% versus 4.5%), and overweight (33.3% versus 15.5%). However, physical
      activity levels were similar to the reference population. Z scores for BMC and
      BMD were reduced, particularly at the ultradistal radius, whereas Z scores for
      weight, body mass index, fat mass, and body fat percentage were increased. Mean
      (SD) BMC Z scores were lowest at the ultradistal radius, -0.66 (1.22), where
      symptoms to milk were associated with reduced values (p < 0.009) and overweight
      with increased values (p < 0.003). CONCLUSIONS: Our results suggest site-specific
      weakness and high body weight contribute to fracture risk in children and
      adolescents who fracture their forearms repeatedly. These findings are consonant
      with work showing adult Colles fractures increase as ultradistal radius BMD falls
      and with evidence that overweight children and adolescents are fracture prone.

PMID- 16294263
TI  - Relationship between changes in BMD and nonvertebral fracture incidence
      associated with risedronate: reduction in risk of nonvertebral fracture is not
      related to change in BMD.
AB  - Whether greater treatment-related changes in BMD result in greater decreases in
      fracture risk is controversial. We analyzed the relationship between BMD change
      and nonvertebral fracture risk in postmenopausal osteoporotic women from the
      risedronate fracture program. Change in BMD did not influence the magnitude of
      risedronate's effect on nonvertebral fractures; the incidence of nonvertebral
      fractures was equally low in treated patients whose BMD increased or decreased.
      INTRODUCTION: In untreated patients, low BMD correlates with increased fracture
      risk. Whether greater increases in BMD induced by anti-osteoporosis drugs are
      related to greater decreases in vertebral fracture risk is controversial, and
      little has been written about the relationship between change in BMD and
      nonvertebral fracture risk. We analyzed the relationship between BMD change and
      nonvertebral fracture incidence using individual patient data from postmenopausal
      osteoporotic women receiving antiresorptive treatment with risedronate. MATERIALS
      AND METHODS: This posthoc analysis combined data from three pivotal risedronate
      fracture endpoint trials. Women received risedronate 2.5 or 5 mg (n = 2,561) or
      placebo (n = 1,418) daily for up to 3 years. BMD and nonvertebral fractures
      confirmed by radiograph (hip, wrist, pelvis, humerus, clavicle, and leg) were
      assessed periodically over 3 years. RESULTS: The incidence of nonvertebral
      fractures in risedronate-treated patients was not different between patients
      whose spine BMD decreased (7.8%) and those whose spine BMD increased (6.4%;
      hazard ratio to subgroup of patients who lost BMD [HR], 0.79; 95% CI, 0.50, 1.25)
      or between those whose femoral neck BMD decreased (7.6%) and those whose femoral
      neck BMD increased (7.5%; HR, 0.93; 95% CI, 0.68, 1.28). The changes in lumbar
      spine and femoral neck BMD explained only 12% (95% CI, 2%, 21%; p = 0.014) and 7%
      (95% CI, 2%, 13%; p = 0.005), respectively, of risedronate's nonvertebral
      fracture efficacy. CONCLUSIONS: For patients treated with risedronate, changes in
      BMD as measured by DXA do not predict the degree of reduction in nonvertebral
      fractures.

PMID- 16294264
TI  - Safety and efficacy of risedronate in patients with age-related reduced renal
      function as estimated by the Cockcroft and Gault method: a pooled analysis of
      nine clinical trials.
AB  - The incidences of osteoporosis and renal insufficiency increase with age. We
      studied the influence of renal function on the safety and efficacy of risedronate
      5 mg daily in osteoporotic women. Risedronate was safe and effective in
      osteoporotic women with mild, moderate, or severe age-related renal impairment.
      INTRODUCTION: The incidences of both osteoporosis and renal insufficiency
      increase with age; thus, the effect of renal impairment on the safety and
      efficacy of osteoporosis treatments is a clinical concern. Risedronate is a
      pyridinyl bisphosphonate well established as safe and effective in the treatment
      and prevention of osteoporosis. Currently, there is little available information
      about the effect of bisphosphonate treatment in patients with renal
      insufficiency. This retrospective analysis was conducted to study the influence
      of renal function on the safety and efficacy of risedronate in a population of
      osteoporotic women. MATERIALS AND METHODS: Combined data from nine randomized,
      double-blind, placebo-controlled phase III risedronate trials were analyzed. The
      patients in these studies had no markedly abnormal laboratory parameters that
      were considered clinically significant and no evidence of significant disease.
      This analysis included patients who received placebo (n = 4,500) or risedronate 5
      mg (n = 4,496) for up to 3 years (average duration of exposure, 2 years) and who
      had renal impairment (creatinine clearance [CrCl] < 80 ml/min). CrCl was
      estimated by the Cockcroft and Gault method, based on age, weight, and serum
      creatinine. Patients were categorized as having mild (CrCl >or=50 to <80 ml/min),
      moderate (CrCl >or=30 to <50 ml/min), or severe (CrCl < 30 ml/min) renal
      impairment. RESULTS: Of the patients studied, renal impairment at baseline was
      mild in 48% (mean [range] serum creatinine, 0.9 [0.4-1.6] mg/dl), moderate in 45%
      (1.1 [0.6-1.9] mg/dl), and severe in 7% (1.3 [0.7-2.7] mg/dl). In both the
      placebo and risedronate treatment groups, the patients with the most severe renal
      impairment were older and had more severe osteoporosis. The incidences of overall
      adverse events and of renal function-related adverse events were similar in the
      placebo and risedronate 5 mg groups regardless of renal function. Furthermore,
      evaluation of changes from baseline in serum creatinine revealed no difference in
      renal function between the placebo and risedronate 5 mg groups in any of the
      renal impairment subgroups at any time-point. In all three subgroups, risedronate
      effectively preserved BMD and reduced the incidence of vertebral fractures.
      CONCLUSIONS: These findings show that risedronate is safe and effective in
      osteoporotic women with age-related mild, moderate, or severe renal impairment.

PMID- 16294265
TI  - Critical role of beta3 integrin in experimental postmenopausal osteoporosis.
AB  - We show that mice lacking beta3 integrin are protected from OVX-induced bone
      loss. Using a lentiviral-based strategy to express beta3 mutants in beta3(-/-)
      mice, we also show that beta3(S752), but not beta3(Y747/Y759), is important for
      osteoclastic bone resorption in vivo. INTRODUCTION: Mice lacking the beta3
      integrin have dysfunctional osteoclasts and therefore accumulate bone mass with
      age. Thus, the alphavbeta3 integrin is a potential anti-osteoporosis target.
      Identifying components of the beta3 integrin that determine its function in vivo
      is essential for therapeutically exploiting the antiresorptive properties of
      alphavbeta3. MATERIALS AND METHODS: We used DXA and histomorphometry to assess
      bone loss after ovariectomy in wildtype and beta3 integrin null mice. We used
      lentiviral vectors carrying various human beta3 (hbeta3) integrin constructs to
      transduce beta3(-/-) bone marrow and reconstituted lethally irradiated beta3(-/-)
      mice with the transduced marrow. The expressed constructs include the intact
      integrin and two mutants, namely hbeta3(Y747F/Y759F) and hbeta3(S752P), each of
      which induces the bleeding dyscrasia, Glanzmann's thrombasthenia, in humans. Two
      months after transplantation, the expression of hbeta3 was measured by flow
      cytometry of marrow-derived macrophages. Osteoclast differentiation and function
      were assessed ex vivo by TRACP and actin-ring staining, respectively.
      Reconstituted mice were ovariectomized, and bone loss was assessed by DXA,
      histomorphometry, and serum TRACP5b assay. RESULTS: beta3(-/-) mice are protected
      from ovariectomy-induced bone loss, showing no difference in BMD compared with
      sham-operated controls. We successfully expressed hbeta3 integrins in beta3(-/-)
      hosts using lentiviral transduction of bone marrow. Two months after
      transplantation, 25-35% of marrow-derived macrophages expressed the hbeta3
      constructs. Similar to its effect in vitro, hbeta3(WT) completely rescued the
      osteoclast and platelet phenotype of beta3(-/-) mice. Whereas platelet function
      remained deranged in beta3(-/-) mice overexpressing hbeta3(Y747F/Y759F),
      osteoclast function was fully restored. In contrast, beta3(-/-) mice expressing
      hbeta3(S752P) continued to exhibit prolonged bleeding times and dysfunctional
      osteoclasts in vitro and ex vivo. Most importantly, hbeta3(WT) and
      hbeta3(Y747F/Y759F) transplanted mice underwent equivalent ovariectomy-induced
      bone loss, whereas, like those bearing the control vector, hbeta3(S752P)
      transplanted mice were protected. CONCLUSIONS: Functional beta3 integrin is
      required for ovariectomy-induced bone loss. beta3(S752), but not
      beta3(Y747/Y759), is critical for osteoclast function in vivo.

PMID- 16294267
TI  - Growth without growth hormone receptor: estradiol is a major growth hormone
      independent regulator of hepatic IGF-I synthesis.
AB  - The role of estrogens in the regulation of pubertal growth independently of GH
      and its receptor was studied in male mice with disrupted GHRKO. E(2) rescued
      skeletal growth rates in GHRKO associated with an increase in hepatic and serum
      IGF-I. These data show that E(2) rescues pubertal growth during GH resistance
      through a novel mechanism of GHR-independent stimulation of hepatic IGF-I
      production. INTRODUCTION: Growth hormone (GH) and estrogen play a pivotal role in
      pubertal growth and bone mineral acquisition. Estrogens can affect GH secretion
      and thereby provide a GH-dependent mechanism for their effects on skeletal
      growth. It is presently unclear if or to what extent estrogens are able to
      regulate pubertal growth and bone mineral accrual independently of GH and its
      receptor. MATERIALS AND METHODS: Estradiol (E(2); 0.03 mug/day by subcutaneous
      silastic implants) was administered to orchidectomized (ORX) male mice with
      disrupted GHR (GHRKO) and corresponding WTs during late puberty (6-10 weeks).
      Longitudinal and radial bone growth, IGF-I in serum and its expression in liver,
      muscle, and bone, and liver gene expression were studied by histomorphometry,
      RIA, RT-PCR, microarrays, and Western blotting, respectively. RESULTS: E(2)
      stimulated not only longitudinal (femur length and growth plate thickness) and
      radial growth (cortical thickness and periosteal perimeter), but also rescued
      longitudinal and periosteal growth rates in ORX GHRKO, whereas no significant
      changes occurred in WT. E(2) thereby upregulated serum IGF-I and liver IGF-I
      synthesis (+21% and +52%, respectively) in ORX GHRKO, whereas IGF-I synthesis in
      femur or muscle was unaffected. Study of the underlying mechanism of the
      stimulation of hepatic IGF-I expression showed that E(2) restored downregulated
      receptor signaling systems, such as the estrogen receptor alpha and the prolactin
      receptor. E(2) thereby recovered the Janus kinase (JAK)/signal transducers and
      activators of transcription (STAT) pathway as evidenced by a significantly
      increased activation of the transcription factor STAT5 in ORX GHRKO. CONCLUSIONS:
      Our data show a stimulation of skeletal growth through upregulation of hepatic
      IGF-I by a hormone other than GH. E(2) rescues pubertal skeletal growth during GH
      resistance through a novel mechanism of GHR-independent stimulation of IGF-I
      synthesis in the liver.

PMID- 16294266
TI  - Periosteal progenitor cell fate in segmental cortical bone graft
      transplantations: implications for functional tissue engineering.
AB  - A murine segmental femoral bone graft model was used to show the essential role
      of donor periosteal progenitor cells in bone graft healing. Transplantation of
      live bone graft harvested from Rosa 26A mice showed that approximately 70% of
      osteogenesis on the graft was attributed to the expansion and differentiation of
      donor periosteal progenitor cells. Furthermore, engraftment of BMP-2-producing
      bone marrow stromal cells on nonvital allografts showed marked increases in
      cortical graft incorporation and neovascularization, suggesting that gene
      enhanced, tissue engineered functional periosteum may improve allograft
      incorporation and repair. INTRODUCTION: The loss of cellular activity in a
      structural bone allograft markedly reduces its healing potential compared with a
      live autograft. To further understand the cellular mechanisms for structural bone
      graft healing and repair and to devise a therapeutic strategy aimed at enhancing
      the performance of allograft, we established a segmental femoral structural bone
      graft model in mice that permits qualitative and quantitative analyses of graft
      healing and neovascularization. MATERIALS AND METHODS: Using this segmental
      femoral bone graft model, we transplanted live isografts harvested from Rosa 26A
      mice that constitutively express beta-galactosidase into their wildtype control
      mice. In an attempt to emulate the osteogenic and angiogenic properties of
      periosteum, we applied a cell-based, adenovirus-mediated gene therapy approach to
      engraft BMP-2-producing bone marrow stromal cells onto devitalized allografts.
      RESULTS: X-gal staining for donor cells allowed monitoring the progression of
      periosteal progenitor cell fate and showed that 70% of osteogenesis was
      attributed to cellular proliferation and differentiation of donor progenitor
      cells on the surface of the live bone graft. Quantitative muCT analyses showed a
      3-fold increase in new bone callus formation and a 6.8-fold increase in
      neovascularization for BMP-2/stromal cell-treated allograft compared with control
      acellular allografts. Histologic analyses showed the key features of autograft
      healing in the BMP-2/stromal cell-treated allografts, including the formation of
      a mineralized bone callus completely bridging the segmental defects, abundant
      neovascularization, and extensive resorption of bone graft. CONCLUSIONS: The
      marked improvement of healing in these cellularized allografts suggests a
      clinical strategy for engineering a functional periosteum to improve the
      osteogenic and angiogenic properties of processed allografts.

PMID- 16294268
TI  - Genetic background influences cortical bone response to ovariectomy.
AB  - Peak bone mass is genetically determined, but little is known about the
      heritability of bone loss. Inbred mice were ovariectomized at 16 weeks of age and
      killed at three time-points after surgery. We found that the variation in
      estrogen deficit-related cortical bone loss is genetically determined.
      INTRODUCTION: Variability in adult bone morphology and composition among three
      inbred mouse strains-A/J, C57BL/6J (B6), and C3H/HeJ (C3H)-suggests that they
      gain bone in different ways during growth. In this study, we tested the
      hypothesis that these strains would also lose bone differently after estrogen
      deprivation. MATERIALS AND METHODS: Female A/J, B6, and C3H mice (N = 70/strain)
      were either ovariectomized (OVX) or sham-operated at 16 weeks of age and killed
      at 4, 8, and 16 weeks after surgery. Cortical bone histomorphometry was performed
      on right femoral mid-diaphyseal cross-sections. Mechanical properties were
      determined by loading left femoral mid-diaphyses to failure in four-point
      bending. RESULTS: Both OVX-A/J and OVX-B6 mice showed a 7-8% decrease in cortical
      area and width because of an 8-10% marrow expansion at 16 weeks after OVX. This
      bone loss did not affect mechanical properties in OVX-A/J femurs, but maximum
      load and stiffness in OVX-B6 decreased slightly (9%) at 4 and 8 weeks, and
      markedly (14-19%) at 16 weeks after OVX. In contrast, OVX-C3H showed a
      significant decrease in cortical area and width (6-7%) at 4 weeks after OVX and a
      slight decrease in the subperiosteal area (4%) at 8 weeks after OVX, although
      marrow area remained unchanged. Surprisingly, intracortical resorption spaces,
      which were present in sham-C3H mice, were greatly increased (+195%) in OVX-C3H
      mice at 8 weeks after OVX. Bone strength and stiffness in OVX-C3H mice decreased
      markedly (12-14%) at 4 weeks but slightly (8-10%) at 8 weeks after OVX. All
      indices except intracortical pore area in OVX-C3H mice returned to sham levels at
      16 weeks after OVX. CONCLUSIONS: The magnitude, timing, and location of cortical
      bone loss after OVX varied significantly among A/J, B6, and C3H mice. The
      subsequent changes in mechanical properties after OVX depended on the variable
      bone patterns as well as the size and shape of the adult bone. Our results
      suggest that patterns of estrogen deficit-associated cortical bone loss are
      genetically determined.

PMID- 16294269
TI  - Sympathetic nervous system does not mediate the load-induced cortical new bone
      formation.
AB  - The contribution of the SNS to bone's response to mechanical loading is unclear.
      Using a noninvasive model of axial loading of the murine tibia, we found that
      sciatic neurectomy enhances load-induced new cortical bone formation and that
      pharmacological blockade of the SNS does not affect such responses, indicating
      that the SNS does not mediate the osteogenic effects of loading in cortical bone.
      INTRODUCTION: There is increasing evidence that the sympathetic nervous system
      (SNS) contributes to the regulation of bone mass and may influence remodeling by
      modulating bones' response to mechanical load-bearing. The aim of this study was
      to examine the effect of sciatic neurectomy (SN) on the changes in cortical bone
      formation induced in response to mechanical loading and to investigate whether
      the SNS is directly involved in such load-induced responses. MATERIALS AND
      METHODS: Accordingly, load-induced responses were compared in tibias of growing
      and adult control C57Bl/J6 mice and in mice submitted to unilateral SN;
      noninvasive axial loading that induced 2,000 microstrain on the tibia lateral
      midshaft cortex was applied cyclically, 5 or 100 days after surgery, for 7
      minutes, 3 days/week for 2 weeks, and mice received calcein on the third and last
      days of loading. Tibias were processed for histomorphometry, and transverse
      confocal images from diaphyseal sites were analyzed to quantify new cortical bone
      formation. Chemical SNS inactivation was achieved by prolonged daily treatment
      with guanethidine sulfate (GS) or by the introduction of propranolol in drinking
      water. RESULTS: Our results show that new cortical bone formation is enhanced by
      loading in all tibial sites examined and that load-induced periosteal and
      endosteal new bone formation was greater in the SN groups compared with sham
      operated controls. This SN-related enhancement in load-induced cortical bone
      formation in tibias was more pronounced 100 days after neurectomy than after 5
      days, suggesting that longer periods of immobilization promote a greater
      sensitivity to loading. In contrast, the increases in new bone formation induced
      in response to mechanical loading were similar in mice treated with either GS or
      propranolol compared with controls, indicating that inactivation of the SNS has
      no effect on load-induced cortical new bone formation. CONCLUSIONS: This study
      shows that SN, or the absence of loading function it entails, enhances loading
      related new cortical bone formation in the tibia independently of the SNS.

PMID- 16294270
TI  - DMP1 depletion decreases bone mineralization in vivo: an FTIR imaging analysis.
AB  - The role of DMP1 in mineralization was analyzed by comparing bone mineral and
      matrix properties in dmp1-null female mice to heterozygous and wildtype controls
      by FTIR imaging spectroscopy. The observed decreased mineral content in dmp1 null
      mice indicates a key role for dmp1 in bone mineralization. Indirect effects of
      DMP1 on other systems also determine the KO phenotype. INTRODUCTION: Dentin
      matrix protein 1 (DMP1), an acidic phosphorylated extracellular matrix protein,
      is highly expressed in mineralized tissues. In vitro, DMP1 peptides can promote
      or inhibit mineralization depending on the extent of phosphorylation, the peptide
      size, and concentration. To clarify the biological function of DMP1 protein on in
      vivo mineralization, this study analyzed bone properties of dmp1 knockout (KO)
      mice compared with heterozygous (HET) and wildtype (WT) controls. MATERIALS AND
      METHODS: Tibias from dmp1 KO and age-, sex-, and background-matched HET and WT
      mice at 4 and 16 weeks (N(total) = 60) were examined by Fourier transform
      infrared imaging (FTIRI), histology (n = 6 per genotype and age; N = 36), and
      geometry by muCT (n = 4 per genotype and age; N = 24). Serum ionic calcium and
      phosphate concentrations were also determined. RESULTS: The mineral-to-matrix
      ratios (spectroscopic parameter of relative mineral content) were significantly
      lower in dmp1 KO mice tibias compared with WT and HET at 4 and 16 weeks. The
      mineral crystallinity (crystal size/perfection) was significantly increased in
      dmp1 KO and HET mice relative to WT. Collagen cross-link ratios (a spectroscopic
      parameter related to the relative amounts of nonreducible/reducible collagen
      cross-links) in dmp1 KO were not significantly different from WT and HET. Based
      on muCT, cortical bone cross-sectional areas at 16 but not 4 weeks were
      significantly reduced in the KO compared with controls. Maximum, minimum, and
      polar cross-sectional moments of inertia were significantly lower in dmp1 KO than
      in HET at 16 weeks but not at 4 weeks. Histological analysis and muCT 3-D images
      suggested that dmp1 KO mice had osteomalacia. Dmp1 KO mice had significantly
      lower ionic calcium and phosphate concentrations relative to WT, whereas in the
      HET, values for phosphate were equivalent, and calcium values were decreased
      relative to WT values. CONCLUSIONS: The findings of decreased mineral-to-matrix
      ratio and increased crystal size in bones of dmp1 KO mice suggest that DMP1 has
      multiple roles (both direct and indirect) in the regulation of postnatal
      mineralization. We suggest that direct effects on mineral formation, crystal
      growth, and indirect effects on regulation of Ca x P concentrations and matrix
      turnover all contribute to the dominant phenotype in the dmp1 KO mouse.

PMID- 16294271
TI  - A new selective estrogen receptor modulator, CHF 4227.01, preserves bone mass and
      microarchitecture in ovariectomized rats.
AB  - A new SERM, CHF 4227.01, given to 6-month-old female rats immediately after
      ovariectomy, preserved bone mass and bone microarchitecture without affecting
      uterus weight. It also decreased serum cholesterol and fat mass in estrogen
      deficient rats. INTRODUCTION: We tested the effect of a new benzopyran
      derivative, CHF 4227.01, with selective estrogen receptor modulator (SERM)
      activity on bone mass and biomechanics in ovariectomized (OVX) female rats in
      comparison with 17alpha-ethinylestradiol (EST), raloxifene (RLX), and
      lasofoxifene (LFX). MATERIALS AND METHODS: Four doses of CHF 4227.01 (0.001,
      0.01, 0.1, and 1 mg/kg body weight [bw]/day) were administered in OVX animals
      daily by gavage 5 days/week for 4 months. EST was administered at a dose of 0.1
      mg/kg bw/day, whereas RLX and LSX were administered at doses of 1 and 0.1 mg/kg
      bw/day, respectively, by gavage. In one group (Sham), rats were operated but the
      ovaries not removed; another OVX group was treated only with placebo. RESULTS AND
      CONCLUSIONS: Treatment with CHF 4227.01 (1.0 and 0.1 mg/kg bw), EST (0.1 mg/kg
      bw), LFX (0.1 mg/kg bw), or RLX (1.0 mg/kg bw) prevented bone loss on the lumbar
      spine and the proximal femur assessed in vivo by DXA. Volumetric BMD obtained by
      pQCT ex vivo confirmed protection from bone loss in the spine and proximal femur
      among rats treated with CHF 4227.01. This effect was associated with strong
      inhibition of bone resorption both histologically and biochemically. Furthermore,
      CHF 4227.01 preserved trabecular microarchitecture, analyzed by muCT, and
      maintained biomechanical indices of bone strength in the spine and proximal
      femur, effects also observed for RLX, whereas LSX was less protective of
      microarchitecture. CHF 4227.01 treatment did not affect uterine weight, prevented
      the increase in body weight and fat mass seen in OVX animals, and decreased serum
      cholesterol to below the average of intact animals. In conclusion, CHF 4227.01
      exhibits a promising therapeutic and safety profile as a new SERM on both
      skeletal and extraskeletal outcomes.

PMID- 16294272
TI  - Influence of BMPs on the formation of osteoblastic lesions in metastatic prostate
      cancer.
AB  - The purpose of this study was to evaluate the role of BMPs on the formation of
      metastatic prostate cancer lesions to bone. Our results show that BMPs influence
      the development and progression of osteoblastic lesions and suggest that
      therapies that inhibit BMP activity may reduce the formation and progression of
      osteoblastic lesions. INTRODUCTION: Prostate adenocarcinoma is the leading cause
      of cancer in North American men. The formation of skeletal metastases affects
      approximately 70% of patients with advanced disease, and a majority of these
      patients have osteoblastic lesions. Although BMPs have been found to be expressed
      in multiple oncogenic cell lines, their role in the formation of metastatic
      osteoblastic lesions remains uncharacterized. We hypothesized that BMPs influence
      the development of metastatic osteoblastic lesions associated with prostate
      cancer. MATERIALS AND METHODS: Western blot analysis and RT-PCR was used to
      determine BMP receptor expression on osteoblastic prostate cancer cell lines LAPC
      4 and LAPC-9. Migration, invasion, and cellular proliferation assays were used to
      quantify the effects of BMP-2, -4, and -7 on LAPC-4 cells in vitro. LAPC-9 cells
      alone or transfected with a retrovirus overexpressing noggin were injected into
      the tibias of SCID mice, and the animals were followed for 8 weeks. Tumor size
      was determined by radiographs and direct measurement. Histology was performed at
      the time of death. RESULTS: We determined that BMP receptor mRNA and protein was
      expressed on osteoblastic prostate cancer cell lines LAPC-4 and LAPC-9. In vitro
      studies showed that BMP-2 and -7 stimulated cellular migration and invasion of
      prostate cancer cells in a dose-dependent fashion, although BMP-4 had no effect.
      Noggin inhibited cellular migration and invasion of BMP-2- and -7-stimulated LAPC
      4 cells. LAPC-9 cells implanted into immunodeficient mouse tibias formed an
      osteoblastic lesion with sclerotic bone at 8 weeks. Formation of osteoblastic
      lesions was inhibited by overexpression of noggin by prostate cancer cells
      transduced with a retrovirus containing the cDNA for noggin. CONCLUSIONS: BMPs
      are critical in the formation of the osteoblastic lesions associated with
      prostate cancer metastases, and future treatment strategies that inhibit local
      BMP activity may reduce the formation and progression of osteoblastic lesions.

PMID- 16294273
TI  - Dominant negative N-cadherin inhibits osteoclast differentiation by interfering
      with beta-catenin regulation of RANKL, independent of cell-cell adhesion.
AB  - We studied the effects of dominant negative N-cadherin (NCadDeltaC) expression in
      ST2 cells on their ability to support osteoclastogenesis. Expression of
      NCadDeltaC in ST2 cells did not decrease cell-to-cell adhesion but significantly
      reduced osteoclast formation when co-cultured with BMMs. NCadDeltaC inhibited
      beta-catenin/TCF signaling, resulting in decreased RANKL expression, which could
      contribute to the reduced osteoclast formation. INTRODUCTION: Cadherin is a
      calcium-dependent cell adhesion molecule that plays major roles during embryonic
      development and morphogenesis. Classic cadherins interact with beta-catenin,
      which is also involved in the Wnt signaling pathway. We tested whether disruption
      of N-cadherin function in stromal cells by dominant negative N-cadherin affects
      their ability to support osteoclastogenesis by altering heterotypic interaction
      with osteoclast precursors. MATERIALS AND METHODS: ST2 cells were transduced with
      retrovirus encoding extracellular domain-truncated, dominant negative N-cadherin
      (NCadDeltaC) and co-cultured with bone marrow macrophages (BMMs) to study the
      ability to support osteoclastogenesis. As a downstream target of NCadDeltaC, beta
      catenin/T-cell factor (TCF) transcriptional activity was analyzed using TOPflash
      reporter construct. Real-time RT-PCR analysis and RANKL-luciferase reporter
      assays were performed to study the effects of NCadDeltaC on the osteoprotegerin
      (OPG)/RANKL system. RESULTS: Immunoblotting analysis showed that primary bone
      marrow stromal cells, ST2 cells, and BMMs expressed N-cadherin. Retroviral
      expression of NCadDeltaC in ST2 cells did not significantly inhibit cell adhesion
      but markedly impaired the formation of TRACP(+) osteoclasts (>40%) when co
      cultured with BMMs. However, the inhibition of osteoclastogenesis was not
      reproduced by neutralizing antibody against N-cadherin. Expression of NCadDeltaC,
      however, strongly suppressed beta-catenin/TCF transcriptional activity in ST2
      cells, which was rescued by constitutively active beta-catenin adenovirus (Ad
      DeltaN46 beta-catenin) or constitutively active TCF mutant (pCS2
      VP16DeltabetaXTCF-3). As a potential downstream target of Wnt signaling, we found
      that the expression of RANKL was reduced in ST2 cells expressing NCadDeltaC.
      Moreover, Wnt-3A, Ad DeltaN46 beta-catenin, and VP16DeltabetaXTCF-3 increased the
      expression of RANKL and enhanced the transcriptional activity of mouse RANKL
      promoter in ST2 cells. CONCLUSIONS: Our data suggest that expression of dominant
      negative N-cadherin in ST2 cells suppressed osteoclastogenesis by interfering
      with beta-catenin regulation of RANKL independent of cell-cell adhesion.

PMID- 16294274
TI  - New target genes for NOV/CCN3 in chondrocytes: TGF-beta2 and type X collagen.
AB  - We studied the involvement of NOV/CCN3, whose function is poorly understood, in
      chondrocyte differentiation. NOV was found to upregulate TGF-beta2 and type X
      collagen and to act as a downstream effector of TGF-beta1 in ATDC5 and primary
      chondrocytes. Thus, NOV is a positive modulator of chondrogenesis. INTRODUCTION:
      NOV/CCN3 is a matricellular protein that belongs to the CCN family. A growing
      body of evidence indicates that NOV could play a role in cell differentiation,
      particularly in chondrogenesis. During chick embryo development, NOV expression
      is tightly regulated in cartilage, and a high expression of NOV has been
      associated with cartilage differentiation in Wilms' tumors. However, a precise
      role for NOV and potential target genes of NOV in chondrogenesis are unknown.
      MATERIALS AND METHODS: ATDC5 cells and primary chondrocytes were either treated
      with NOV recombinant protein or transfected with a NOV-specific siRNA to
      determine, using quantitative RT-PCR, the effect of NOV on the expression of
      several molecules involved in chondrocyte differentiation. Stable ATDC5 clones
      expressing NOV were also established to show that NOV was a downstream effector
      of TGF-beta1. RESULTS: We established that NOV/CCN3 expression increases in ATDC5
      cells at early stages of chondrogenic differentiation and precedes the appearance
      of TGF-beta2 and of several chondrocytic markers such as SOX9 or type X collagen.
      When exogenously administered, NOV recombinant protein up-regulates TGF-beta2 and
      type X collagen mRNA levels both in ATDC5 cells and in primary mouse chondrocytes
      but does not influence SOX9 expression. This regulation also occurs at the
      endogenous level because downregulation of NOV expression is correlated with an
      inhibition of TGF-beta2 and type X collagen in primary chondrocytes. Furthermore,
      we found that NOV expression is downregulated when chondrocytes are exposed to
      TGF-beta1-dedifferentiating treatment in chondrocytes, further providing evidence
      that NOV may counteract TGF-beta1 effects on chondrocytes. CONCLUSIONS: This
      study provides the first characterization of two new targets of NOV involved in
      chondrocyte differentiation, shows that NOV acts with TGF-beta1 in a cascade of
      gene regulation, and indicates that NOV is a positive modulator of
      chondrogenesis.

PMID- 16294275
TI  - Estrogen and testosterone use different cellular pathways to inhibit
      osteoclastogenesis and bone resorption.
AB  - Using human peripheral blood CD14(+) osteoclast precursors, we show that
      testosterone directly inhibits osteoclast formation and bone resorption at
      physiological concentrations. Instead, estrogen has no direct effects, whereas
      its action seems to be mediated through osteoblasts by producing osteoprotegerin.
      Both estrogen and testosterone acts through their cognate receptors.
      INTRODUCTION: Estrogen (E2) deficiency is associated with both the development of
      postmenopausal and senile form of osteoporosis in elderly women. Testosterone
      (Te) deficiency, on the other hand, may cause osteoporosis in men. In both sexes,
      osteoporosis is associated with disturbed bone turnover, including increased bone
      resorption caused by enhanced osteoclast formation and increased osteoclast
      activity. However, the mechanisms by which E2 or Te act on bone are not fully
      understood, and one of the central questions is whether these hormones act
      directly on osteoclast precursors or whether their action is mediated through
      osteoblastic cells. MATERIALS AND METHODS: We cultured human peripheral blood
      CD14(+) osteoclast precursors in the presence of RANKL, macrophage-colony
      stimulating factor (M-CSF), TNF-alpha, and dexamethasone to induce them to
      differentiate into osteoclasts. To study the possible osteoblast-mediated
      effects, osteoclast precursors were also co-cultured either with human MG-63 or
      SaOS-2 osteoblast-derived osteosarcoma cells. These cultures were treated with
      10(-8)-10(-12) M of E2 or Te for 7 days. RESULTS: E2 did not have any direct
      effect on osteoclast formation, whereas testosterone inhibited osteoclast
      formation and bone resorption in a dose-dependent manner. In co-cultures, where
      MG-63 or SaOS-2 cells were present, E2 and Te inhibited osteoclast formation in a
      dose-dependent manner. At the same time, E2 and Te treatment in MG-63 or SaOS-2
      cell-containing cultures stimulated significantly the formation of
      osteoprotegerin (OPG) compared with untreated cultures measured by ELISA assay
      from the culture medium. The effects of E2 and Te on osteoclast formation and
      bone resorption were completely antagonized by an E2 receptor (ER) antagonist,
      ICI 182,780, and an androgen receptor (AR) antagonist, flutamide, suggesting ER-
      and AR-mediated mechanisms, respectively, in these cultures. CONCLUSIONS: Te is
      likely to have direct and indirect inhibitory effects on human osteoclast
      formation and bone resorption, whereas the effect of E2 on osteoclast precursors
      and osteoclasts seems to be mediated by osteoblastic cells. Inhibitory effect of
      E2 is associated with the stimulated secretion of OPG by osteoblast-derived
      osteosarcoma cells. Mechanism of action of E2 and Te is mediated by ER and AR,
      respectively.

PMID- 16294276
TI  - Multiple mechanisms are involved in inhibition of osteoblast differentiation by
      PTHrP and PTH in KS483 Cells.
AB  - We examined the mechanism by which PTHrP and PTH inhibit KS483 osteoblastic
      differentiation. We show that PTHrP and PTH inhibit differentiation downstream of
      early BMP signaling and downregulated components of the hedgehog (Hh) signaling
      cascade. In addition, PTHrP and PTH repressed RunX2 and osx expression.
      Overexpression of either gene, however, could not relieve PTHrP and PTH's
      inhibitory actions. Our data suggest that multiple parallel mechanisms are
      involved in the inhibition of osteoblast differentiation and matrix
      mineralization by PTHrP and PTH. INTRODUCTION: PTH-related peptide (PTHrP) and
      PTH are potent inhibitors of osteoblast differentiation in vitro by as yet
      unexplained mechanisms. MATERIALS AND METHODS: We treated murine bone marrow
      stromal cells and the mesenchymal progenitor cell line KS483 with PTHrP and PTH
      in combination with either BMPs or hedgehog (Hh) and measured early and late
      markers of osteoblast differentiation and studied the expression of RunX2 and
      Osterix (osx). In addition, we examined the PTHrP and PTH response in stable
      KS483 cells overexpressing either RunX2 or osx. RESULTS: PTHrP and PTH inhibited
      BMP- and Hh-induced osteogenesis downstream of early BMP signaling and by
      downregulation of components of the Hh signaling cascade. PTHrP and PTH prevented
      the upregulation of RunX2 expression associated with osteoblast differentiation
      in an indirect response. However, PTHrP and PTH could still inhibit
      differentiation, and particularly matrix mineralization, of cells expressing
      RunX2. In addition, PTHrP and PTH potently downregulated osx expression only in
      mature osteoblasts in an intermediate early response, but osx overexpression
      could not relieve the inhibitory effects of PTHrP and PTH on matrix
      mineralization. CONCLUSIONS: Our data suggest that, besides transcriptional
      repression of RunX2 and osx, other mechanisms in parallel with or downstream of
      RunX2 and osx are involved in the inhibition of osteoblast differentiation and
      matrix mineralization by PTHrP and PTH in vitro.

PMID- 16294277
TI  - Regulation of osteoclast apoptosis and motility by small GTPase binding protein
      Rac1.
AB  - The role of Rac1 in osteoclast survival and bone-resorbing activity was examined
      using adenovirus vector expression systems. Rac1 is critically involved in M-CSF
      receptor signaling and mediates survival signaling primarily through PI3K/Akt
      pathways. Rac1 also plays a significant role in bone resorptive activity,
      probably by regulating the motility of osteoclasts. INTRODUCTION: Rac1 is a
      member of Rho family small G-proteins, and recent studies have revealed that it
      mediates anti-apoptotic signals in some types of cells. Rac1 is reported to be
      required for the cytoskeletal organization and bone-resorbing activity of
      osteoclasts, but their roles in osteoclast survival and function are not fully
      elucidated. MATERIALS AND METHODS: We constructed the adenovirus vector carrying
      cDNA of either the dominant negative Rac1 (Rac1(DN)) or constitutively active
      Rac1 (Rac1(CA)) gene, and osteoclast-like cells (OCLs) generated in mouse co
      culture system were infected with these viruses. To examine the role of Rac1 in
      osteoclast survival and function, we performed pit formation assays, survival
      assays, and Western blotting, including an activated-Rac1 pull-down assay using
      adenovirus-infected OCLs. To further clarify the mechanism of Rac1 regulation in
      osteoclast survival, some specific inhibitors and adenovirus vectors of signal
      transduction molecules were used. To quantify membrane movement before and after
      macrophage colony-stimulating factor (M-CSF) treatment, OCLs expressing either
      enhanced green fluorescent protein (EGFP) or Rac1(DN) were recorded with a time
      lapse video microscope. RESULTS: Adenovirus vector-mediated dominant negative
      Rac1 (Rac1(DN)) expression significantly reduced pit formation, and promoted
      their apoptosis. M-CSF rapidly activated Rac1, and the prosurvival effect of M
      CSF for OCLs was abrogated by Rac1(DN) overexpression. Constitutively active Rac1
      enhanced OCL survival, which was completely suppressed by phosphatidylinositol 3'
      kinase (PI3K) inhibitors, whereas a Mek inhibitor had only partial effect.
      Rac1(DN) also partially blocked the activation of Akt induced by the
      overexpressing catalytic subunit of PI3K. Using time-lapse video microscopy, we
      found that Rac1(DN) expression reduced membrane ruffling and the spreading of
      OCLs in response to M-CSF. CONCLUSIONS: Small guanosine triphosphatase (GTPase)
      Rac1 is critically involved in M-CSF receptor signaling and mediates survival
      signaling of osteoclasts primarily by modulating PI3K/Akt pathways. Rac1 also
      plays a significant role in the bone resorptive activity of cells, probably by
      regulating the motility of osteoclasts.

PMID- 16294278
TI  - Histone deacetylase inhibitors promote osteoblast maturation.
AB  - HDIs are potential therapeutic agents for cancer and neurological diseases
      because of their abilities to alter gene expression, induce growth arrest or
      apoptosis of tumors cells, and stimulate differentiation. In this report, we show
      that several HDIs promote osteoblast maturation in vitro and in calvarial organ
      cultures. INTRODUCTION: Histone deacetylase inhibitors (HDIs) are currently in
      phase I and II clinical trials as anticancer agents. Some HDIs are also commonly
      prescribed treatments for epilepsy and bipolar disorders. Although administered
      systemically, the effects of HDIs on osteoblasts and bone formation have not been
      extensively examined. In this study, we investigated the effect of histone
      deacetylase inhibition on osteoblast proliferation and differentiation. MATERIALS
      AND METHODS: MC3T3-E1 cells, calvarial-derived primary osteoblasts, and calvarial
      organ cultures were treated with various commercially available HDIs
      (trichostatin A [TSA], sodium butyrate [NaB], valproic acid [VPA], or MS-275).
      The effects of these inhibitors on cell proliferation, viability, cell cycle
      progression, Runx2 transcriptional activity, alkaline phosphatase production, and
      matrix mineralization were determined. Expression levels of osteoblast maturation
      genes, type I collagen, osteopontin, bone sialoprotein, and osteocalcin in
      response to TSA were measured by quantitative PCR. RESULTS: Concentrations of
      HDIs that caused hyperacetylation of histone H3 induced transient increases in
      osteoblast proliferation and viability but did not alter cell cycle profiles.
      These concentrations of HDIs also increased the transcriptional activity of
      Runx2. TSA accelerated alkaline phosphatase production in MC3T3-E1 cells and
      calvarial organ cultures. In addition, TSA accelerated matrix mineralization and
      the expression of osteoblast genes, type I collagen, osteopontin, bone
      sialoprotein, and osteocalcin in MC3T3-E1 cells. CONCLUSIONS: These studies show
      that histone deacetylase activity regulates osteoblast differentiation and bone
      formation at least in part by enhancing Runx2-dependent transcriptional
      activation. Therefore, HDIs are a potentially new class of bone anabolic agents
      that may be useful in the treatment of diseases that are associated with bone
      loss such as osteoporosis and cancer.

PMID- 16294280
TI  - Spaceflight, weightlessness, and bone loss--what are we measuring?

PMID- 16294279
TI  - Limited rescue of osteoclast-poor osteopetrosis after successful engraftment by
      cord blood from an unrelated donor.
AB  - We report on a case of osteoclast-poor osteopetrosis who received a hematopoietic
      stem cell graft and, despite hematological engraftment, showed little signs of
      response in the skeletal defect. Clinical and laboratory studies supported the
      concept that the bone microenvironment remained abnormal, thus reducing the
      clinical response to transplantation. INTRODUCTION: Osteopetrosis is a rare
      genetic disorder characterized by severely reduced bone resorption resulting from
      a defect in either osteoclast development (osteoclast-poor osteopetrosis) or
      activation (osteoclast-rich osteopetrosis). Patients with osteoclast-rich
      osteopetrosis can be rescued by allogenic hematopoietic stem cell
      transplantation; however, little information exists concerning the success of
      transplantation as a treatment for osteoclast-poor osteopetrosis. We report on a
      child with osteoclast-poor osteopetrosis whose diagnosis was delayed,
      consequently receiving a cord blood transplant from an unrelated donor at the age
      of 8 years. Engraftment was deemed successful by peripheral blood genotyping,
      although >3 years after transplantation there was little rescue of the skeletal
      defect and anemia, and extramedullary hematopoiesis persisted. MATERIALS AND
      METHODS: Peripheral blood mononuclear cells from the osteopetrosis patient,
      before and after transplantation, were used to generate osteoclasts in vitro in
      the presence of macrophage colony-stimulating factor (M-CSF) and RANKL. RESULTS:
      Before transplantation few, small mononuclear osteoclasts formed (F-actin ring
      positive cells, co-localizing with vitronectin receptor [alphavbeta3 integrin]
      and TRACP) associated with occasional, small resorption lacunae. Low levels of
      collagen C-terminal telopeptide (CTx) fragments were released from these cultures
      as assessed by ELISA (CrossLaps; patient, 12.85 nM; control, 448.6 nM). In
      contrast, osteoclasts formed in cultures after transplantation formed to a
      similar degree to control cultures from healthy individuals: large numbers of
      osteoclasts containing numerous nuclei were present, and approximately 50% of the
      surface of bone slices was resorbed, associated with intermediate levels of
      collagen fragment release (116.48 nM). The culture data reflect the
      histopathology and radiological findings and also support previous studies
      showing that neither M-CSF nor RANKL rescues osteoclast-poor osteopetrosis.
      CONCLUSIONS: This is the first case reported in which a successful hematopoietic
      engraftment failed to correct an osteopetrotic skeletal defect, and this finding
      may be credited to the age at which the child was transplanted.

PMID- 16294282
TI  - [Cross-over transplant donors: a question of personal bonding].

PMID- 16294283
TI  - [Stable tachycardia with wide QRS complex in pre-hospital emergency medicine].
AB  - BACKGROUND: Sustained, stable wide QRS-complex tachycardia (WCT) remains a
      diagnostic challenge, because the treatment of supra-ventricular tachycardia
      (SVT) with aberrant conduction differs considerably from that of a ventricular
      tachycardia (VT). A usual recommendation for treating a case of a stable WCT is
      to manage it as if it were VT, in accordance with the consideration of "first do
      no harm". The aim of this study was to determine whether Board-certified
      emergency-physicians are able to differentiate VT from SVT with aberrant
      conduction in a high percentage of cases (> 90%), thus to assure more precise
      prehospital treatment." METHODS: Eight electrocardiograms with WCT (four with
      electrophysiologically proven VT or SVT, respectively) were evaluated in a
      blinded fashion by 64 Board-certified emergency-physicians (23 female, 41 male,
      mean age: 37,8 + 5,1 years). Initially, the diagnosis had to be made without any
      further information. Afterwards the same electrocardiograms were presented again,
      providing important additional information. RESULTS: 55% of the study population
      were able to establish the correct diagnosis merely by evaluating the
      electrocardiogram. Providing the above mentioned additional information, the
      number of correct diagnoses increased to 61%. These results were roughly similar
      in all subgroups, only the subgroup of cardiologists showed a trend to better
      results with correct diagnoses in 68% without and 73 % with additional
      information. None of the subgroups reached the pre-specified cut-off of > or =
      90% correct diagnoses. Specialist status as well as experience in emergency
      medicine had no significant influence on the results, only the subgroup of
      emergency physicians with an experience of more than five years showed a trend
      towards a higher rate of correct diagnosis, compared with the subgroup with less
      than one year experience in emergency medicine. CONCLUSION: In cases of stable
      WCT the evaluation of the electrocardiogram without further information in
      prehospital emergency-medicine leads to unsatisfactory results. The correct
      diagnosis in WCT can be improved by using additional data but the diagnostic
      accuracy is still low. Therefore, the differential diagnosis of stable WCT in
      preclinical emergency-medicine cannot be recommended. Until proven otherwise, any
      stable WCT should be managed as if it were VT.

PMID- 16294284
TI  - [Cross-over kidney transplantation in Germany].
AB  - A donor kidney exchange or cross-over program with exchange of organs between two
      donor-recipient pairs offers a possibility to realise living donor renal
      transplantation in cases of ABO-blood group incompatibility. The German
      transplantation law demands, in contrast to other countries, a close personal
      relationship between living donor and recipient. In this paper, we propose a
      concept based on the generation of a close personal relationship between donor
      recipient pairs that allows cross-over renal donor transplantation considering
      the statement of the responsible medical-ethical institutions and the German
      transplantation law.

PMID- 16294285
TI  - [Pericardiac cyst].

PMID- 16294286
TI  - [Solid actinomycosis of the liver].
AB  - HISTORY: A 41-year -old man was admitted for resection of several liver segments,
      because a malignant tumor was suspected. He had two years previously sustained
      blunt trauma to the abdomen and chest. At that time a hematoma of the liver had
      been diagnosed by ultrasound and computed tomography. Follow-up imagings showed
      an increase in its size. On admission the patient had only slight right upper
      abdominal pain; laboratory tests were unremarkable. INVESTIGATIONS: Computed
      tomography confirmed the suspected diagnosis of a cholangiocellular carcinoma
      with possible abdominal wall infiltration. Tumor markers were negative. TREATMENT
      AND COURSE: An extensive partial liver resection was performed. Histological
      examination of the resected specimen revealed solid actinomycosis of the liver.
      After prolonged high dosage penicillin treatment all signs and symptoms resolved
      without further problems. Postoperative serology provided no evidence of active
      systemic actinomycosis. CONCLUSION: This case demonstrates the difficulty of
      diagnosing and treating solid actinomycosis.

PMID- 16294288
TI  - [Multiple chemical sensitivity (MCS): a review].

PMID- 16294289
TI  - [Gerocomy -- gerontology -- geriatrics. The naming of a modern medical
      discipline].
AB  - 300 years ago, the lawyer Theodosius Schopffer coined the notion gerontology. On
      this occasion, this paper offers terms and corresponding concepts of gerontology
      which arose in the western tradition: 1. From the Graeco-Roman antiquity until
      1750, gerocomy (the care for the elderly) was defined as a branch of medicine,
      but in practice almost did not exist. Basically, it provided instructions for a
      way of life in conformity with the physiological circumstances of elderly people.
      Its implementation was left to the patient. Furthermore, in the early modern
      times medical treatises dealt more frequently with diseases of the elderly and
      their therapy. The gerokomia succeeded in evolving a specific technical
      literature. Yet it failed to get institutionalized. 2. At the beginning of the
      20th century, Ignaz Nascher interpreted geriatrics as a counterpart to pediatrics
      and opposed it to a clinical-pathological consideration of old age before 1900.
      He aimed at the exploration and treatment of old age as an autonomous
      physiological entity. Under the influence of the demographic transformation the
      institutionalization of geriatrics as a interdisciplinary branch within medicine
      could be realized relatively soon. 3. Around 1930, we experience the recreation
      of the notion gerontology, initially restricted to medical gerontology. However,
      with the integration of the non-medical sciences of old age the spectrum and the
      objectives changed. Today gerontology signifies on a international level a
      generic term or independent scientific discipline beside medicine. This evolution
      corresponds with the intentions pursued 300 years ago.

PMID- 16294290
TI  - [Care duty of the physician to present examination findings to private health
      insurance. Decision of the High Court, Mainz, 2/10/2005].

PMID- 16294287
TI  - [Fever of unknown origin in the 21st century: infectious diseases].
AB  - Fever of unknown origin (FUO) is a rare but important disease. The definition of
      FUO has not changed in the last 50 years. Classical FUO is defined by an illness
      of at least 3 weeks duration with fever greater than 38 masculine C, and no
      established diagnosis after 1 week of hospital investigation. The causes of FUO
      can be divided in four categories: infectious diseases, noninfectious
      inflammatory diseases, neoplasms, and others (miscellaneous). Recent studies have
      surprisingly shown that despite improved diagnostic procedures the percentage of
      patients with FUO, in which no diagnosis after intensive investigations in
      specialized centres can be found, has increased. However, finding the correct
      diagnosis in FUO is essential for these patients for psychological and vital
      reasons. Therefore and because of economic reasons patients with FUO should be
      investigated in specialized centres with a department for rheumatology and
      infectious diseases.

PMID- 16294291
TI  - [Combination of anticoagulants with platelet aggregation inhibitors?].

PMID- 16294292
TI  - [Experiences with the realisation of the innovative study designs using the
      example of the HOPE study -- concerning the contribution in DMW Supplement
      2/2005].

PMID- 16294294
TI  - Autocrine motility factor/glucose-6-phosphate isomerase is a possible predictor
      of metastasis in bone and soft tissue tumours.
AB  - In order to assess the involvement of autocrine motility factor (AMF) in
      mesenchymal tumours, AMF protein and mRNA expression was analysed in tumours,
      tumour-like lesions, and other lesions of bone and soft tissue.
      Immunohistochemical analysis of 200 cases revealed positive staining in 72.5% of
      the cases, suggesting that AMF is a widely expressed protein. Chordoid,
      chondroid, and muscular tumours revealed higher immunoreactivity in both benign
      and malignant tumours. Immunoblotting analysis corroborated the results of
      immunohistochemistry. Generally, malignant tumours revealed higher expression of
      AMF than benign tumours of the same histopathological lineage, except for
      dermatofibroma/dermatofibrosarcoma protuberans. However, mRNA levels were not
      concordant with protein levels, and sarcomas that displayed higher mRNA and lower
      protein expression levels showed a trend for distant metastasis. In cultured
      cells, AMF was secreted and detected in conditioned culture medium. Furthermore,
      when proteasome inhibitors were added to cells in order to examine the changes in
      turnover rates, these compounds did not significantly alter the intracellular
      levels of AMF protein. On the basis of these overall findings, it is suggested
      that a particular subset of sarcomas secrete AMF, rather than degrading this
      protein at a higher turnover rate. This secreted AMF presumably enhances their
      cell motility through an autocrine effect and eventually causes increased
      metastatic potential. Collectively, AMF was observed in a wide spectrum of
      lesions of mesenchymal tissue, supporting the notion that it is involved in
      various cellular functions, including proliferation, differentiation, metabolism,
      and metastasis. In addition, higher expression of its mRNA may indicate higher
      levels of protein secretion and define a particularly aggressive group of tumours
      with high metastatic potential.

PMID- 16294295
TI  - Simplified current decoupler for microchip capillary electrophoresis with
      electrochemical and pulsed amperometric detection.
AB  - There is a need to develop broadly applicable, highly sensitive detection methods
      for microchip CE that do not require analyte derivatization. LIF is highly
      sensitive but typically requires analyte derivatization. Electrochemistry
      provides an alternative method for direct analyte detection; however, in its most
      common form, direct current (DC) amperometry, it is limited to a small number of
      easily oxidizable or reducible analytes. Pulsed amperometric detection (PAD) is
      an alternative waveform that can increase the number of electrochemically
      detectable analytes. Increasing sensitivity for electrochemical detection (EC)
      and PAD requires the isolation of detection current (nA) from the separation
      current (muA) in a process generally referred to as current decoupling. Here, we
      present the development of a simple integrated decoupler to improve sensitivity
      and its coupling with PAD. A Pd microwire is used as the cathode for decoupling
      and a second Au or Pt wire is used as the working electrode for either EC or PAD.
      The electrode system is easy to make, requiring no clean-room facilities or
      specialized metallization systems. Sensitive detection of a wide range of
      analytes is shown to be possible using this system. Using this system we were
      able to achieve detection limits as low as 5 nM for dopamine, 74 nM for
      glutathione, and 100 nM for glucose.

PMID- 16294296
TI  - Effect of buffer flow on DNA separation in a microfabricated electrophoresis
      system.
AB  - An adequate buffer reservoir is one essential component of an electrophoresis
      system, providing current carrying ions and maintaining constant pH. In a
      microfabricated DNA separation system with on-chip electrodes, the amount of
      buffer used is limited by the design of the device; the buffer continuity can be
      easily disturbed by the production of bubbles. Continuously flowing 1 x Tris
      borate-EDTA (TBE) buffer over the electrodes at the cathodic end solves both
      problems. This flow increases the resolution for ssDNA primer separations (21 and
      25 bases) to a maximum value of 1.4 within a distance of 1.2 cm, about four times
      higher than that without flow. Similar improvement has been achieved for dsDNA
      separation (20 bp ladder; BioRad) at a distance of only 0.4 cm, giving baseline
      resolution for bands from 20 to 240 bp. We have also investigated the effect of
      buffer concentration on resolution, and no similar improvement can be obtained by
      merely increasing the buffer concentration without flow.

PMID- 16294297
TI  - High-throughput enzyme assay on a multichannel microchip using optically gated
      sample introduction.
AB  - To meet the requirements for high-throughput screening for drug discovery
      research, it is very important to develop techniques with the ability of
      performing multiple enzyme assays simultaneously. Using optically gated sample
      introduction on a multichannel microchip, multiple enzyme assays have been
      demonstrated in four parallel channels. The hydrolysis of fluorescein mono-beta-D
      galactopyranoside by beta-galactosidase and the inhibition of this reaction by
      the competitive inhibitor phenylethyl beta-D-thiogalactoside were initially
      studied to determine the effect of system movement using the voice coil actuator
      on the enzyme assay reaction. The results from these two studies are consistent
      with the results from the assay using a single-channel microchip, and they
      demonstrate that the system using optically gated sample introduction on
      multichannel microchip can be used to perform multiple enzyme assays. Three
      unique enzyme assays were also performed in different channels, which show this
      technique could be competitive for high-throughput screening in drug discovery
      with other traditional techniques.

PMID- 16294298
TI  - Multipoint linkage disequilibrium mapping using case-control designs.
AB  - Case-control study has been and continues to be one of the most popular designs
      in epidemiology. More recently, this design has been adopted to test for
      candidate genes when searching for disease genetic etiology. In this report, we
      present a multipoint linkage disequilibrium (LD) mapping approach with the focus
      on estimating the location of the target trait locus. It builds upon a
      representation, which shows that the difference between a case and a control in
      probabilities of carrying the target allele of a marker is proportional to that
      of the trait locus and that the proportionality factor is simply a measure of LD
      between the trait locus and the marker. Our method has the desired properties
      that (1) there is no need to specify phases of genotypic data with multiple
      markers, (2) it provides an estimate of location of the disease locus along with
      sampling uncertainty to help investigators to narrow chromosomal regions, and (3)
      a single test statistic is provided to test for LD in the framed region rather
      than testing the hypothesis one marker at a time. Our simulation work suggests
      that the proposed method performs well in terms of bias and coverage probability.
      Extension of the proposed method to account for confounding and genetic
      heterogeneity is discussed. We apply the proposed method to a published case
      control data set for cystic fibrosis.

PMID- 16294299
TI  - A sparse marker extension tree algorithm for selecting the best set of haplotype
      tagging single nucleotide polymorphisms.
AB  - Single nucleotide polymorphisms (SNPs) play a central role in the identification
      of susceptibility genes for common diseases. Recent empirical studies on human
      genome have revealed block-like structures, and each block contains a set of
      haplotype tagging SNPs (htSNPs) that capture a large fraction of the haplotype
      diversity. Herein, we present an innovative sparse marker extension tree (SMET)
      algorithm to select optimal htSNP set(s). SMET reduces the search space
      considerably (compared to full enumeration strategy), and therefore improves
      computing efficiency. We tested this algorithm on several datasets at three
      different genomic scales: (1) gene-wide (NOS3, CRP, IL6 PPARA, and TNF), (2)
      region-wide (a Whitehead Institute inflammatory bowel disease dataset and a UK
      Graves' disease dataset), and (3) chromosome-wide (chromosome 22) levels. SMET
      offers geneticists with greater flexibilities in SNP tagging than lossless
      methods with adjustable haplotype diversity coverage (phi). In simulation
      studies, we found that (1) an initial sample size of 50 individuals (100
      chromosomes) or more is needed for htSNP selection; (2) the SNP tagging strategy
      is considerably more efficient when the underlying block structure is taken into
      account; and (3) htSNP sets at 80-90% phi are more cost-effective than the
      lossless sets in term of relative power, relative risk ratio estimation, and
      genotyping efforts. Our study suggests that the novel SMET algorithm is a
      valuable tool for association tests.

PMID- 16294301
TI  - Estimating the additive genetic effect of the X chromosome.
AB  - We propose a method for efficient estimation of the additive genetic effect of
      the X chromosome with explicit modeling of eutherian-type dosage compensation.
      The theoretical derivation of the variance-components model for X-linked loci is
      reviewed in detail. We develop a model of dosage compensation that allows for
      both incomplete and heterogeneous lyonization, the existence of which is
      suggested by recent expression studies. Modeling this relationship, especially in
      the limit cases of complete or absent compensation, allows estimation of the X
      effect as a single parameter for ease of comparison to other sources of variance.
      We present simulation studies to estimate the power and computational efficiency
      of our proposed method.

PMID- 16294302
TI  - Proteomic analysis of chlorosome-depleted membranes of the green sulfur bacterium
      Chlorobium tepidum.
AB  - Green sulfur bacteria are obligate anaerobic phototrophs, which in addition to
      outer and plasma membranes contain chlorosomes. The analysis of the membrane
      proteome of Chlorobium tepidum from chlorosome-depleted membranes is described in
      this study. The membranes were purified by sucrose density centrifugation and
      characterized by 1-DE and 2-DE coupled with MS, absorption spectroscopy, and
      electron microscopy. 1-DE and 2-DE were employed to analyze the membrane proteins
      and to characterize the capabilities of the methods. Solubilization of the
      membrane proteins prior to 2-DE was improved by using a series of zwitterionic
      detergents. Based on the resolved spots after 2-DE, the combination of
      amidosulfobetaine 14 with Triton X-100 is more efficient than the combination of
      CHAPS, N-decyl-N,N-dimethyl-3-ammonio-1-propane sulfonate, and Triton X-100. From
      the application of 1-DE and 2-DE, 167 and 202 unique proteins were identified,
      respectively, using PMF by MALDI-TOF MS. Both methods resulted in the detection
      of 291 different proteins of which only 88 were predicted membrane proteins,
      indicating the limitation of membrane protein detection after separation with
      electrophoresis methods. In addition, 53 of these proteins were identified as
      outer membrane proteins.

PMID- 16294303
TI  - Disulfide proteome yields a detailed understanding of redox regulations: a model
      study of thioredoxin-linked reactions in seed germination.
AB  - Accumulating evidence suggests that redox regulations play important roles in a
      broad spectrum of biological processes. Recently, Yano et al. developed a
      disulfide proteome technique that comprehensively visualizes redox change in
      proteins. In this paper, using the disulfide proteome, we examined rice bran and
      identified fragments of embryo-specific protein and dienelactone hydrolase as
      putative targets of thioredoxin. Also, monitoring of the endogenous and
      recombinant effects of thioredoxin on rice bran proteins and supporting in vivo
      observations propose a mechanism of redox regulation in seed germination, in
      which thioredoxin activates cysteine protease with a concurrent unfolding of its
      substrate, the embryo-specific protein. Our findings suggest that thioredoxin
      controls the lifetime of specific proteins effectively by regulating the redox
      reactions coordinately. The model study demonstrates that the disulfide proteome
      technique is useful not only for identifying targets of thioredoxin, but also for
      clarify the detailed mechanism of redox regulation.

PMID- 16294304
TI  - Proteome analysis of mitochondrial outer membrane from Neurospora crassa.
AB  - The mitochondrial outer membrane mediates numerous interactions between the
      metabolic and genetic systems of mitochondria and the rest of the eukaryotic
      cell. We performed a proteomic study to discover novel functions of components of
      the mitochondrial outer membrane. Proteins of highly pure outer membrane vesicles
      (OMV) from Neurospora crassa were identified by a combination of LC-MS/MS of
      tryptic peptide digests and gel electrophoresis of solubilized OMV proteins,
      followed by their identification using MALDI-MS PMF. Among the 30 proteins found
      in at least three of four separate analyses were 23 proteins with known functions
      in the outer membrane. These included components of the import machinery (the TOM
      and TOB complexes), a pore-forming component (porin), and proteins that control
      fusion and fission of the organelle. In addition, proteins playing a role in
      various biosynthetic pathways, whose intracellular location had not been
      established previously, could be localized to the mitochondrial outer membrane.
      Thus, the proteome of the outer membrane can help in identifying new mitochondria
      related functions.

PMID- 16294305
TI  - Rapid protein identification using direct infusion nanoelectrospray ionization
      mass spectrometry.
AB  - Current protein identification techniques are largely based on MALDI-TOF mass
      fingerprinting and LC-ESI MS/MS sequence tag analysis. Here we describe an
      improved method for rapid protein identification that uses direct infusion
      nanoelectrospray quadrupole time-of-flight (nanoESI QTOF) MS. Protein digests
      were analyzed without LC separation using nanoESI on a QSTAR XL MS/MS system in
      information dependent data acquisition mode. The protein identification
      conditions and parameters were extensively evaluated with in-solution and in-gel
      digested protein samples. Rapid identification of proteins was achieved and
      compared directly to the results obtained on the same samples using nanoflow HPLC
      MS/MS on the QSTAR system. The increased throughput, reproducibility, the high
      data quality, and the ease of use make the direct infusion system an efficient
      and affordable technique for protein identification analysis.

PMID- 16294306
TI  - Identification of prion protein binding proteins by combined use of far-Western
      immunoblotting, two dimensional gel electrophoresis and mass spectrometry.
AB  - The cellular prion protein (PrP(C)), a highly conserved glycoprotein
      predominantly expressed by neuronal cells, can convert into an abnormal isoform
      (PrP(Sc)) and provoke a transmissible spongiform encephalopathy. In spite of many
      studies, the physiological function of PrP(C) remains unknown. Recent findings
      suggest that PrP(C) is a multifunctional protein participating in several
      cellular processes. Using recombinant human PrP as a probe, we performed far
      Western immunoblotting (protein overlay assay) to detect cellular PrP(C)
      interactors. Brain extracts of wild-type and PrP knockout mice were screened by
      far-Western immunoblotting for PrP-specific interactions. Subsequently, putative
      ligands were isolated by 2-DE and identified by MALDI-TOF MS, enabling
      identification of heterogeneous nuclear ribonucleoprotein A2/B1 and aldolase C as
      novel interaction partners of PrP(C). These data provide the first evidence of a
      molecule indicating a mechanism for the predicted involvement of PrP(C) in
      nucleic acid metabolisms. In summary, we have shown the successful combination of
      2-DE with far-Western immunoblotting and MALDI-TOF MS for identification of new
      cellular binding partners of a known protein. Especially the application of this
      technique to investigate other neurodegenerative diseases is promising.

PMID- 16294307
TI  - Proteome profile changes that are differentially regulated by lipid and protein
      phosphatase activities of tumor suppressor PTEN in PTEN-expressing U-87 MG human
      glioblastoma cells.
AB  - The phosphatase and tensin homolog tumor suppressor (PTEN) belongs to a class of
      "gatekeeper" tumor suppressors together with p53, retinoblastoma and adenomatous
      polyposis. It is considered one of the most important tumor suppressors in the
      post p53 era. Previously to identify the molecules involved in the signaling
      network regulated by PTEN using proteomic tools, we reported global proteome
      profiles at different time points using the PTEN inducible NIH3T3 cells (Kim, S.
      y., Kim, Y. S., Bahk, Y. Y., Mol. Cells 2003, 15, 396-405). However, the system
      had a critical limitation that NIH3T3 cell has endogenous wild-type PTEN and,
      thus to be exact, the induced PTEN could not give the answer about the real
      physiological roles of this tumor suppressor. Here, to find out PTEN-related
      protein network we have established various PTEN (wild-type, an activity inert
      C124G, and a lipid phosphatase deficient G129E)-expressing cell clones in U-87 MG
      human glioblastoma cells lacking detectable PTEN as a result of genetic lesions.
      In this biological context, we compared their morphological and expression
      patterns, and proteome images of each PTEN-expressing cell clone by 2-DE followed
      by identification with MALDI-TOF MS. We obtained some pieces of evidence that
      morphological change by PTEN expression is mediated by its protein phosphatase
      activity and their growth rate by the lipid phosphatase activity. The proteomic
      approaches showed that 30 proteins possibly correlated with PTEN's protein
      phosphatase activity (13 down-regulated and 17 up-regulated) and 20 with the
      lipid phosphatase activity (14 down-regulated and 6 up-regulated) were
      identified. Taken together, we conclude that the comparative analysis of proteome
      from various PTEN-expressing cells has yielded interpretable data to elucidate
      the protein network directly and/or indirectly caused by individual phosphatase
      activities of PTEN in vivo.

PMID- 16294308
TI  - Proteome analysis of human amnion and amniotic fluid by two-dimensional
      electrophoresis and matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry.
AB  - Proteome analysis by 2-DE and PMF by MALDI-TOF MS was performed on human amnion
      and amniotic fluid at term. Ninety-two soluble and nineteen membrane proteins
      were identified from amnion. Thirty-five proteins were identified from amniotic
      fluid. Calgranulin A and B were found in all patients infected with Ureaplasma
      urealyticum, but not in any of the patients without infection, indicating that
      they are potential markers of intrauterine infection. Identity of calgranulin A
      and B was confirmed by MALDI-TOF/TOF MS. This study represents the first
      extensive analysis of the human amnion and amniotic fluid proteome at term and
      demonstrates that 2-DE and MALDI-TOF MS is a useful tool for identifying
      clinically significant biomarkers of problematic pregnancies.

PMID- 16294309
TI  - Towards the proteome of Burkholderia cenocepacia H111: setting up a 2-DE
      reference map.
AB  - Polyphasic-taxonomic studies of the past decade have shown that the Burkholderia
      cepacia complex (Bcc) comprises at least nine species, which share a high degree
      of 16S rDNA (98-100%) sequence similarity but only moderate levels of DNA-DNA
      hybridization. Members of the Bcc are well known as opportunistic pathogens of
      plants, animals and humans but also as biocontrol and bioremediation agents. In
      this study intra-, surface-associated and extracellular proteins of B.
      cenocepacia H111, which was isolated from a cystic fibrosis patient, were
      examined by 2-DE coupled to MALDI-TOF MS. MS and MS/MS data were searched against
      a database comprising all currently available annotated proteins of genetically
      closely related strains. In total 642 proteins spots were successfully identified
      corresponding to 390 different protein species, which were classified into
      functional categories. The majority of these proteins could be linked to
      housekeeping functions in energy production, amino acid metabolism, protein
      folding, post-translational modification and turnover, and translation.
      Noteworthy is the fact that a significant number of truly secreted and membrane
      proteins were identified in the extracellular and surface-associated sub
      proteomes. This indicates that the pre-fractionation protocol used in this study
      is a highly valuable strategy for unravelling the cellular location of the
      identified proteins.

PMID- 16294310
TI  - A protein network for phospholipid synthesis uncovered by a variant of the tandem
      affinity purification method in Escherichia coli.
AB  - In prokaryotes, acyl carrier protein (ACP) is a cofactor central to a myriad of
      syntheses, including fatty acid and phospholipid synthesis. To fulfill its
      function, ACP must therefore interact with a multitude of different enzymes,
      which includes the thioesterase YbgC. We found a specific interaction between ACP
      and YbgC whose thioesterase activity has been demonstrated in vitro on acyl-CoA
      derivatives, but whose physiological function in bacteria remains unknown.
      Therefore, YbgC could be a thioesterase active on some specific acyl-ACPs. We
      then assigned a function to the ACP/YbgC pair by employing a proteomic approach
      derived from tandem affinity purification, the split tag method. This technique
      allowed us to purify proteins interacting with ACP and YbgC proteins at the same
      time. Interactions with PlsB, a sn-glycerol-3-phosphate acyltransferase and PssA,
      a phosphatidylserine synthase, were identified and validated, showing that YbgC
      is involved in phospholipid metabolism. Furthermore, using an in vivo bacterial
      two-hybrid interaction analysis, we showed for the first time that enzymes of the
      phospholipid synthesis pathway form a complex in the inner membrane. Taken
      together, these results describe an integrated protein network that could be
      involved in the coordination of phospholipid metabolism.

PMID- 16294311
TI  - Detergent-free caveolae proteome suggests an interaction with ER and
      mitochondria.
AB  - Recent proteomic studies of detergent resistant membrane fractions have begun to
      characterize the protein composition of caveolae and lipid rafts. The methods
      used in most of these studies, however, are not able to distinguish between
      plasma membrane and internal membrane lipid domains. Here we used a non-detergent
      method for obtaining fractions enriched in caveolae derived from the plasma
      membrane of multiple cell types. Unexpectedly, the proteins in the caveolae
      proteome suggest these lipid domains may interact with elements of ER and
      mitochondria. A comparison of the partial proteome we obtained with other
      published reports identifies 26 proteins that are candidate marker proteins for
      identifying caveolae in multiple cell types.

PMID- 16294312
TI  - Nanostructures and molecular force bases of a highly sensitive capacitive
      immunosensor.
AB  - While biosensors have been constructed using various strategies, there is no
      report describing nanostructures of antibody-immobilized electrode interface in
      an immunosensor. Here, atomic force microscopy (AFM) and electrochemistry
      analyses were employed to construct and characterize the nanostructures and
      electrochemistry of biosensing surface that was created by a sequential self
      assembling of bioactive aminobenzenthiol oligomer (o-ABT), glutareldehyde and
      anti-transferrin (anti-Tf) antibody on the electrode gold surface. Under AFM, a
      complete coverage of bioactive o-ABT interface could be achieved by anti-Tf
      antibody at an optimal concentration. The anti-Tf antibody immobilized on
      electrode surface of the immunosensor exhibited globular-shape topography with
      some degree of aggregation. Extensive force-curve analysis allowed mapping the
      functional spots of the anti-Tf immunosensor. Surprisingly, although
      immunosensing surface was fully covered by anti-Tf antibodies at the optimal
      concentration, only about 52% of coated anti-Tf antibody molecules (spots) on the
      electrode surface were able to specifically capture or bind Tf antigen under AFM.
      Despite limited functional spots, however, the anti-Tf immunosensor was highly
      specific and sensitive for sensitizing Tf antigen in solution. The anti-Tf
      molecules on the immunosensor exhibited a greater molecular force bound to holo
      Tf (iron-containing form of Tf) than that to apo-Tf (iron-absent form of Tf).
      Consistently, the anti-Tf immunosensor had a greater electrochemical capacity to
      sensitize apo-Tf than holo-Tf, supporting the molecular force-based finding by
      AFM. Thus, the present study elucidated the nanostructures and molecular force
      bases for the immunosensing capacity of a highly sensitive capacitive
      immunosensor.

PMID- 16294313
TI  - Enhanced phosphopeptide isolation by Fe(III)-IMAC using 1,1,1,3,3,3
      hexafluoroisopropanol.
AB  - IMAC can be used to selectively enrich phosphopeptides from complex peptide
      mixtures, but co-retention of acidic peptides together with the failure to retain
      some phosphopeptides restricts the general utility of the method. In this study
      Fe(III)-IMAC was qualitatively and quantitatively assessed using a panel of
      phosphopeptides, both synthetic and derived from proteolysis of known
      phosphoproteins, to identify the causes of success and failure in the application
      of this technique. Here we demonstrate that, as expected, peptides with a more
      acidic amino acid content are generally more efficiently purified and detected by
      MALDI-MS after Fe(III)-IMAC than those with a more basic content. Modulating the
      loading buffer used for Fe(III)-IMAC significantly affects phosphopeptide binding
      and suggests that conformational factors that lead to steric hindrance and
      reduced accessibility to the phosphate are important. The use of 1,1,1,3,3,3
      hexafluoroisopropanol is shown here to significantly improve Fe(III)-IMAC
      enrichment and subsequent detection of phosphopeptides by MALDI-MS.

PMID- 16294314
TI  - 2-D reference map of Bacillus anthracis vaccine strain A16R proteins.
AB  - Bacillus anthracis has always been an important pathogen because it can cause
      lethal inhalational anthrax, and may be used as a bioweapon or by bioterrorists.
      In this study, a 2-DE reference map and database of B. anthracis A16R was
      constructed. In total, 534 spots were processed, and 406 spots representing 299
      proteins were identified. Gel-estimated pIs and molecular masses mostly matched
      well with their theoretical predictions, but some discrepancies also existed.
      Spot and protein corresponding analysis revealed that post-translational
      modifications might be common in B. anthracis. Through the MASCOT search, the
      similarity of B. anthracis, B. cereus and B. thuringiensis was further verified
      by protein level and a possible annotation error in B. anthracis strain Ames 0581
      genome was found. Proteins of energy metabolism, fatty acid and phospholipid
      metabolism, protein synthesis, and cellular processes represented a large part of
      the most abundant proteins. At the same time, 27 hypothetical proteins were
      experimentally proved. There were 28 proteins also identified as spore
      composition in recently spore-related research, which indicated that they might
      play some roles in different phases such as growth, sporulation and outgrowth.
      Maps and information about all identified proteins are available on the Internet
      at http://www.mpiib-berlin.mpg.de/2D-PAGE and http://www.proteomics.com.cn.

PMID- 16294315
TI  - MS characterization of multiple forms of alpha-amylase in human saliva.
AB  - Alpha-amylase is a major and well-characterized component of human saliva. Recent
      proteomic studies suggested that this protein could be observed in more than
      twenty spots on 2-D gels of salivary proteins. The aim of this work was to
      investigate this unexpected redundancy. 2-D gel electrophoresis was combined with
      systematic MALDI-TOF MS analysis. More than 140 protein spots identifying the
      alpha-amylase were shown to constitute a stable but very complex pattern. Careful
      analysis of mass spectra and simultaneous hierarchical clustering of the observed
      peptides and of the electrophoretic features of spots allowed one to define three
      major groups. A main class grouping 90 spots was shown to correspond to full
      length alpha-amylases that can be assumed to include isoforms and post
      translationally modified forms, a subset of this class being demonstrated to be N
      glycosylated. A second group included short alpha-amylases that are differently
      truncated in a non-random manner, very likely in the oral cavity. The last class
      grouped alpha-amylase forms showing both the N- and C-terminal sequences of the
      enzyme but displaying a molecular weight that was up to 50% lower than that of
      the native protein. It is speculated that the last group of alpha-amylase spots
      could correspond to proteins submitted to internal deletions prior to the
      secretion.

PMID- 16294319
TI  - Effect of chlorpromazine on bone sialoprotein (BSP) gene transcription.
AB  - Bone sialoprotein (BSP), an early marker of osteoblast differentiation. Whereas
      physical forces may play an important role in the regulation of bone cell
      function, little is known about how cells are able to sense mechanical loads.
      Chlorpromazine, a tranquilizing agent for treatments of psychiatric disorders,
      mimics hypotonic stress and causes membrane deformation. Application of 10
      microg/ml of chlorpromazine suppressed BSP mRNA levels after 12 and 24 h in
      osteoblast-like ROS17/2.8 cells and rat stromal bone marrow cells (SBMC-D8).
      Chlorpromazine (10 microg/ml) decreased luciferase activity of the construct
      (pLUC3; -116 to +60 of the rat BSP gene promoter) after 12 h, the effect was
      inhibited by the tyrosine kinase inhibitor herbimycin A (HA) and MAP kinase
      kinase inhibitor U0126. Introduction of 2-bp mutation in the pLUC3 construct
      showed that the chlorpromazine effects were mediated by cAMP response element
      (CRE) and FGF2 response element (FRE). In gel shift assays, using radiolabeled
      double-stranded CRE and FRE oligonucleotides, which revealed decreased binding of
      nuclear proteins from chlorpromazine-stimulated cells. These studies, therefore,
      show that chlorpromazine suppresses BSP gene transcription through tyrosine and
      MAP kinases-dependent pathways and that the chlorpromazine effects are mediated
      by CRE and FRE elements in the proximal promoter of the BSP gene.

PMID- 16294320
TI  - The alpha1 subunit of GABAA receptor is repressed by c-myc and is pro-apoptotic.
AB  - The c-myc oncoprotein plays a critical role in the regulation of cellular
      proliferation and apoptosis. To mediate these biological functions, a variety of
      target genes are activated or repressed by c-myc, but few genes have yet been
      identified that directly mediate c-myc's role in proliferation or apoptosis.
      During a screen for genes that are repressed by c-myc, we identified the alpha1
      subunit of gamma aminobutyric acid receptor (GABAAR-alpha1) as a novel target of
      c-myc. GABAAR is the major inhibitory neurotransmitter receptor in the mammalian
      central nervous system and is involved in developmental events in the brain, such
      as neurite outgrowth, neuronal survival, neuronal migration, and proliferation.
      We show here that GABAAR-alpha1 expression is rapidly and directly repressed by c
      myc. GABAAR-alpha1 expression is elevated in c-myc null cells and upregulation of
      GABAAR-alpha1 correlates with downregulation of c-myc protein expression during
      neuronal cell differentiation. We also show that overexpression of GABAAR-alpha1
      causes apoptosis, which is blocked by the coexpression of Bcl-2 or Bcl-XL.
      Induction of apoptosis is specific for the alpha1 subunit, since neither the
      beta1 or beta2 subunits of GABAAR induced apoptosis. Derepression of GABAAR
      alpha1 expression upon downregulation of c-myc represents a unique apoptotic
      mechanism and a distinct function for the alpha1 subunit, independent of its role
      as a component of the GABAAR in the plasma membrane. In addition, the regulation
      of GABAAR-alpha1 expression by c-myc provides a potential direct role for the Myc
      proteins in neurological processes and neurodegenerative disorders.

PMID- 16294321
TI  - Tumor metastasis in an orthotopic murine model of head and neck cancer: possible
      role of TGF-beta 1 secreted by the tumor cells.
AB  - In an orthotopic murine model of head and neck cancer, combined subcutaneous and
      intratumoral vaccination with recombinant vaccinia virus expressing interleukin-2
      (rvv-IL-2) induced significant tumor regression early on therapy. However, its
      efficacy was restricted by recurrent tumor growth and loco-regional metastases.
      In this study, we explored the mechanism of tumor metastasis. We compared the
      levels of expression of a number of molecules involved in tumor metastasis, which
      included transforming growth factor-beta1 (TGF-beta1), E-cadherin, matrix
      metalloproteinases (MMPs): MT1-MMP, MMP-2, MMP-9, their tissue inhibitors
      (TIMPs): TIMP-1/TIMP-2, and pro-angiogenic factors CD31, VEGF-R2, and iNOS
      between primary and metastatic tumors by real-time RT-PCR and
      immunohistochemistry. We detected spontaneous lymph node and tongue metastasis.
      Metastasis was delayed in rvv-IL-2 treated mice. Cultured tumor cells expressed
      negligible amount of TGF-beta1. Untreated or metastatic tumors, on the other
      hand, expressed high levels of TGF-beta1 and secreted TGF-beta1 in the sera of
      tumor-bearing mice. Levels of TGF-beta1 in the sera suddenly jumped at the time
      when tumor metastasis started. In the metastatic tumors, levels of MT1-MMP, MMP
      2, and MMP-9 were significantly elevated (P < 0.001), while levels of TIMP-1/TIMP
      2 and E-cadherin were decreased (P < 0.001) compared to control or primary
      tumors. Levels of CD31, VEGF-R2, and iNOS were also significantly elevated in the
      metastatic lesions (P < 0.001). The concurrence of high levels of TGF-beta1 in
      the sera, expression of proteins involved in metastasis and initiation of
      metastasis suggested possible role of TGF-beta1 in on setting the metastatic
      cascade in this model.

PMID- 16294322
TI  - Beyond the cell cycle: a new role for Cdk6 in differentiation.
AB  - Over 10 years ago, cdk6 was identified as a new member in a family of vertebrate
      cdc-2 related kinases. This novel kinase was found to partner with the D-type
      cyclins and to possess pRb kinase activity in vitro and has since been understood
      to function solely as a pRb kinase in the regulation of the G(1) phase of the
      cell cycle. In the past 2 years, several independent studies in multiple cell
      types have indicated a novel role for cdk6 in differentiation. For example, cdk6
      expression must be reduced to allow proper osteoblast and osteoclast
      differentiation, forced cdk6 expression blocked differentiation of mouse
      erythroid leukemia cells and cdk6 expression in primary astrocytes favors the
      expression of progenitor cell markers. Since exit from the cell cycle is a
      necessary step in terminal differentiation, down-regulation of a mitogenic factor
      may be expected in this process, however it is surprising that this association
      has not been previously uncovered and that it is apparently not shared with cdk4,
      long understood to be a functional homolog of cdk6. The mechanism of cdk6
      function in differentiation is not understood, but it may extend beyond the
      established role of cdk6 as a pRb kinase. As this story unfolds it will be
      important to discover if the function of cdk6 in differentiation is pRb-dependent
      or pRb-independent, since pRb has long been established as a key factor in
      initiating and maintaining cell cycle exit during differentiation.

PMID- 16294323
TI  - Hippocalcin increases phospholipase D2 expression through extracellular signal
      regulated kinase activation and lysophosphatidic acid potentiates the hippocalcin
      induced phospholipase D2 expression.
AB  - We have previously isolated a 22 kDa protein from a rat brain which was found to
      be involved in activating phospholipsae D (PLD), and identified the protein as
      hippocalcin through sequence analysis. Nevertheless, the function of hippocalcin
      for PLD activation still remains to be resolved. Here, we proposed that
      hippocalcin was involved in extracellular signal-regulated kinase (ERK)-mediated
      PLD2 expression. To elucidate a role of hippocalcin, we made hippocalcin
      transfected NIH3T3 cells and showed that the expression of PLD2 and basal PLD
      activity were increased in hippocalcin transfected cells. We performed PLD assay
      with dominant negative PLD2 (DN-PLD2) and hippocalcin co-transfected cells. DN
      PLD2 suppressed increase of basal PLD activity in hippocalcin transfected cells,
      suggesting that increased basal PLD activity is due to PLD2 over-expression.
      Hippocalcin is a Ca2+-binding protein, which is expressed mainly in the
      hippocampus. Since it is known that lysophosphatidic acid (LPA) increases
      intracellular Ca2+, we investigated the possible role of hippocalcin in the LPA
      induced elevation of intracellular Ca2+. When the intracellular Ca2+ level was
      increased by LPA, hippocalcin was translocated to the membrane after LPA
      treatment in hippocalcin transfected cells. In addition, treatment with LPA in
      hippocalcin transfected cells markedly potentiated PLD2 expression and showed
      morphological changes of cell shape suggesting that increased PLD2 expression
      acts as one of the major factors to cause change of cell shape by making altered
      membrane lipid composition. Hippocalcin-induced PLD2 expression potentiated by
      LPA in hippocalcin transfected cells was inhibited by a PI-PLC inhibitor, U73122
      and a chelator of intracellular Ca2+, BAPTA-AM suggesting that activation of
      hippocalcin caused by increased intracellular Ca2+ is important to induce over
      expression of PLD2. However, downregulation of PKC and treatment of a chelator of
      extracellular Ca2+, EGTA had little or no effect on the inhibition of hippocalcin
      induced PLD2 expression potentiated by LPA in the hippocalcin transfected cells.
      Interestingly, when we over-express hippocalcin, ERK was activated, and treatment
      with LPA in hippocalcin transfected cells significantly potentiated ERK
      activation. Specific inhibition of ERK dramatically abolished hippocalcin-induced
      PLD2 expression. Taken together, these results suggest for the first time that
      hippocalcin can induce PLD2 expression and LPA potentiates hippocalcin-induced
      PLD2 expression, which is mediated by ERK activation.

PMID- 16294324
TI  - The effect of hydroxyapatite nanocrystals on microvascular endothelial cell
      viability and functions.
AB  - To favor bone reconstitution with biomaterials endothelial cells should maintain
      proper functions to drive angiogenesis. To this aim nanocrystals of
      hydroxyapatite (HA) have been synthesized and characterized on endothelial cells.
      Microvascular endothelial cells have been exposed to stoichiometric HA
      nanocrystals. Cell morphology and organization of cytoskeletal proteins have been
      monitored by SEM analysis and immunofluorescence. Biochemical markers of
      physiological and pathological responses of endothelial cells, endothelial
      constitutive nitric oxide synthase, and cycloxygenase-2 (ecNOS and COX-2,
      respectively) have been measured by immunofluorescence. Crystallized HA sustained
      endothelial survival without any cytotoxic effect. At the observation with SEM,
      endothelial cell morphology was maintained in the presence of HA. The
      localization and organization of beta-actin documented the formation of stress
      fibers, indicating an activation of endothelial cells induced by HA nanocrystals.
      Immunohistochemistry for biochemical key signaling pathways in endothelium
      demonstrated that nanocrystals of HA maintained the expression of ecNOS and did
      not increase COX-2 expression. In conclusion, the present findings indicate that
      HA nanocrystals exhibit high biocompatibility for microvascular endothelium. In
      the presence of HA nanocrystals endothelial cells maintain biochemical markers of
      healthy endothelium. They do not acquire a proinflammatory or thrombogenic
      phenotype, but express markers of functioning endothelium that might contribute
      to angiogenesis.

PMID- 16294325
TI  - The effects of short-term stimulation on fibroblast spreading in an in vitro 3D
      system.
AB  - Although the short-term effects of mechanical and biochemical stimulation on cell
      protein and DNA production have recently begun to be evaluated using 3D models,
      the effects that such stimulation have on cell morphology and adaptation remains
      unclear. Using a custom-built bioreactor, we were able to create a systematic
      model to examine the short-term effects of stimulation on cell morphology in a 3D
      model, specifically by evaluating cell spreading as the short-term indicator of
      cell adaptation. Fibroblasts were seeded on a porous poly(L-lactic acid) scaffold
      and cultured in a computerized bioreactor for 24 h under various uniaxial strains
      (0, 0.6, 3, 6%) and frequencies (0.0125, 0.125 Hz). Also, the effects of
      transforming growth factor (TGF-beta1) (1, 10, 100 ng/mL) were examined on
      static, nonstimulated cells-scaffold constructs after 24 h. Fibroblasts that had
      been subjected to mechanical stretching were found to exhibit significantly more
      spreading than the static control group. Conversely, TGF-beta1 between 1 and 100
      ng/mL did not produce any significant difference in fibroblast spreading from the
      control groups after 24 h. Collectively, the findings suggest that cell
      morphology and adaptation may be affected by short-term mechanical stimulation,
      as seen by increased cell spreading by the fibroblasts under these experimental
      conditions.

PMID- 16294326
TI  - Microarray and phosphokinase screenings leading to studies on ERK and JNK
      regulation of connective tissue growth factor expression by angiotensin II 1a and
      bradykinin B2 receptors in Rat1 fibroblasts.
AB  - Rat1 fibroblasts stably transfected with the rat angiotensin II (AngII) AT1a and
      bradykinin (BK) B2 receptor cDNAs gained the ability to bind Ang II and BK. Wild
      type Rat1 cells bound neither ligand. Exposure to either effector led to
      characteristic Galphai and Galphaq signal cascades, the release of arachidonic
      acid (ARA), and the intracellular accumulation of inositol phosphates (IP).
      Microarray analyses in response to BK or AngII showed that both receptors
      markedly induce the CCN family genes, CTGF (CCN2) and Cyr61 (CCN1), as well as
      the vasculature-related genes, Cnn1 and Egr1. Real time PCR confirmed the
      increased expression of connective tissue growth factor (CTGF) mRNA. Combined
      sequence-based analysis of gene promoter regions with statistical prevalence
      analyses identified CREB, SRF, and ATF-1, downstream targets of ERK, and JNK, as
      prominent products of genes that are regulated by ligand binding to the BK or
      AngII receptors. The binding of AngII or BK markedly stimulated the
      phosphorylation and thus the activation of ERK2, JNK, and p38MAPK. A BKB2R and an
      AT1aR chimera which displayed only negligible G-protein-related signaling were
      constructed. Both mutant receptors continued to activate these kinases and
      stimulate CTGF expression. Inhibitors of ERK1/2 and JNK but not p38MAPK inhibited
      the BK- and AngII-stimulated expression of CTGF in cells expressing either the WT
      or mutant receptors, illustrating that ERK and JNK participate in the control of
      CTGF expression in a manner that appears to be independent of G-protein.
      Conversely, addition of BK or AngII to the cell line expressing WT AT1aR and
      BKB2R downregulated the expression of collagen alpha1(I) (COL1A1) mRNA. However,
      these effectors did not have this effect in cells expressing the mutant
      receptors. Thus, a robust G-protein related response is necessary for BK or AngII
      to affect COL1A1 expression.

PMID- 16294327
TI  - Curcumin blocks activation of pancreatic stellate cells.
AB  - Activated pancreatic stellate cells (PSCs) play a pivotal role in the
      pathogenesis of pancreatic fibrosis and inflammation. Inhibition of activation
      and cell functions of PSCs is a potential target for the treatment of pancreatic
      fibrosis and inflammation. The polyphenol compound curcumin is the yellow pigment
      in curry, and has anti-inflammatory and anti-fibrotic properties. We here
      evaluated the effects of curcumin on the activation and cell functions of PSCs.
      PSCs were isolated from rat pancreas tissue and used in their culture-activated,
      myofibroblast-like phenotype unless otherwise stated. The effects of curcumin on
      proliferation, alpha-smooth muscle actin gene expression, monocyte
      chemoattractant protein (MCP)-1 production, and collagen expression were
      examined. The effect of curcumin on the activation of freshly isolated cells in
      culture was also assessed. Curcumin inhibited platelet-derived growth factor
      (PDGF)-induced proliferation, alpha-smooth muscle actin gene expression,
      interleukin-1beta- and tumor necrosis factor (TNF)-alpha-induced MCP-1
      production, type I collagen production, and expression of type I and type III
      collagen genes. Curcumin inhibited PDGF-BB-induced cyclin D1 expression and
      activation of extracellular signal-regulated kinase (ERK). Curcumin inhibited
      interleukin-1beta- and TNF-alpha-induced activation of activator protein-1 (AP-1)
      and mitogen-activated protein (MAP) kinases (ERK, c-Jun N-terminal kinase (JNK),
      and p38 MAP kinase), but not of nuclear factor-kappaB (NF-kappaB). In addition,
      curcumin inhibited transformation of freshly isolated cells to myofibroblast-like
      phenotype. In conclusion, curcumin inhibited key cell functions and activation of
      PSCs.

PMID- 16294328
TI  - Cell growth-dependent subcellular localization of p8.
AB  - p8 is a stress-induced protein, biochemically related to the architectural factor
      HMG-I/Y, overexpressed in many cancers and required for tumor expansion. The
      molecular mechanisms by which p8 may exert its effect in aspects of growth is
      unknown. Using immunocytochemistry, we found that p8 presents nuclear
      localization in sub-confluent cells, but it localizes throughout the whole cell
      in high density grown cells. Cells arrested in Go/G1, either by serum deprivation
      or by hydroxyurea treatment, show a nucleo-cytoplasmic localization of p8,
      whether in the rest of the cell cycle stages of actively dividing cells the
      localization is nuclear. A comparison of p8 sequences from human to fly predicts
      a conserved bipartite nuclear localization sequence (NLS). The putative NLS has
      been demonstrated to be functional, since nuclear import is energy dependent
      (inhibited by sodium azide plus 2-deoxyglucose), and fusion proteins GFP-p8 and
      GFP-NLSp8 localize to the nucleus, whereas GFP-p8NLSmut in which with Lys 65, 69,
      76, and 77 mutated to Ala localized to the whole cell. p8 localization does not
      involve the CRM1 transporter, since it is insensitive to leptomycin B. Inhibitors
      of MAPK pathways did not affect p8 subcellular localization. The inhibition of
      deacetylation with Trichostatin A promotes cytoplasmic accumulation of p8. The
      results suggest that p8 growth stage-dependent localization is regulated by
      acetylation, that p8 is not free within the cell but forming part of a complex
      and that it may exert a role in both subcellular localizations.

PMID- 16294329
TI  - SimFold energy function for de novo protein structure prediction: consensus with
      Rosetta.
AB  - Predicting protein tertiary structures by in silico folding is still very
      difficult for proteins that have new folds. Here, we developed a coarse-grained
      energy function, SimFold, for de novo structure prediction, performed a benchmark
      test of prediction with fragment assembly simulations for 38 test proteins, and
      proposed consensus prediction with Rosetta. The SimFold energy consists of many
      terms that take into account solvent-induced effects on the basis of
      physicochemical consideration. In the benchmark test, SimFold succeeded in
      predicting native structures within 6.5 A for 12 of 38 proteins; this success
      rate was the same as that by the publicly available version of Rosetta (ab initio
      version 1.2) run with default parameters. We investigated which energy terms in
      SimFold contribute to structure prediction performance, finding that the
      hydrophobic interaction is the most crucial for the prediction, whereas other
      sequence-specific terms have weak but positive roles. In the benchmark, well
      predicted proteins by SimFold and by Rosetta were not the same for 5 of 12
      proteins, which led us to introduce consensus prediction. With combined decoys,
      we succeeded in prediction for 16 proteins, four more than SimFold or Rosetta
      separately. For each of 38 proteins, structural ensembles generated by SimFold
      and by Rosetta were qualitatively compared by mapping sampled structural space
      onto two dimensions. For proteins of which one of the two methods succeeded and
      the other failed in prediction, the former had a less scattered ensemble located
      around the native. For proteins of which both methods succeeded in prediction,
      often two ensembles were mixed up.

PMID- 16294330
TI  - Left-right lineage analysis of AV cushion tissue in normal and laterality
      defective Xenopus hearts.
AB  - The majority of complex congenital heart defects occur in individuals who are
      afflicted by laterality disease. We hypothesize that the prevalence of
      valvuloseptal defects in this population is due to defective left-right
      patterning of the embryonic atrioventricular (AV) canal cushions, which are the
      progenitor tissue for valve and septal structures in the mature heart. Using
      embryos of the frog Xenopus laevis, this hypothesis was tested by performing left
      right lineage analysis of myocytes and cushion mesenchyme cells of the superior
      and inferior cushion regions of the AV canal. Lineage analyses were conducted in
      both wild-type and laterality mutant embryos experimentally induced by
      misexpression of ALK4, a type I TGF-beta receptor previously shown to modulate
      left-right axis determination in Xenopus. We find that abnormalities in overall
      amount and left-right cell lineage composition are present in a majority of ALK4
      induced laterality mutant embryos and that much variation in the nature of these
      abnormalities exists in embryos that exhibit the same overall body situs. We
      propose that these two parameters of cushion tissue formation-amount and left
      right lineage origin-are important for normal processes of valvuloseptal
      morphogenesis and that defective allocation of cells in the AV canal might be
      causatively linked to the high incidence of valvuloseptal defects associated with
      laterality disease.

PMID- 16294331
TI  - Crystal structure of ScpB from Chlorobium tepidum, a protein involved in
      chromosome partitioning.
AB  - Structural maintenance of chromosome (SMC) proteins are essential in chromosome
      condensation and interact with non-SMC proteins in eukaryotes and with
      segregation and condensation proteins (ScpA and ScpB) in prokaryotes. The highly
      conserved gene in Chlorobium tepidum gi 21646405 encodes ScpB (ScpB_ChTe). The
      high resolution crystal structure of ScpB_ChTe shows that the monomeric structure
      consists of two similarly shaped globular domains composed of three helices sided
      by beta-strands [a winged helix-turn-helix (HTH)], a motif observed in the C
      terminal domain of Scc1, a functionally related eukaryotic ScpA homolog, as well
      as in many DNA binding proteins.

PMID- 16294334
TI  - Insulin-like growth factor actions during development of neural stem cells and
      progenitors in the central nervous system.
AB  - Insulin-like growth factor-I (IGF-I) plays a key role in normal development.
      Recent studies show that IGF-I exerts a wide variety actions in the central
      nervous system during development as well as in adulthood. This report reviews
      recent developments on IGF-I actions and its mechanisms in the central nervous
      system, with a focus on its actions during the development of neural stem cells
      and progenitors. Available data strongly indicate that IGF-I shortens the length
      of the cell cycle in neuron progenitors during embryonic life and has an
      influence on the growth of all neural cell types. The phosphatidylinositol-3
      kinase/Akt and mitogen-activated protein kinase pathways seem to be the
      predominant mediators of IGF-I-stimulated neural cell proliferation and survival.
      IGF-I actions, however, likely depend on cell type, developmental stage, and
      microenvironmental milieu.

PMID- 16294335
TI  - Integration of genetically modified adult astrocytes into the lesioned rat spinal
      cord.
AB  - Combination of ex vivo gene transfer and cell transplantation is now considered
      as a potentially useful strategy for the treatment of spinal cord injury. In a
      perspective of clinical application, autologous transplantation could be an
      option of choice. We analyzed the fate of adult rat cortical astrocytes
      genetically engineered with a lentiviral vector transplanted into a lesioned rat
      spinal cord. Cultures of adult rat cortical astrocytes were infected with an HIV
      1-derived vector (TRIP-CMV-GFP) and labeled with the fluorescent dye Hoechst.
      Transfected and labeled astrocyte suspension was injected at T11 in rats in which
      spinal cord transection at T7-T8 levels had been carried out 1 week earlier. Six
      weeks after grafting, the animals were sacrificed and transplants were retrieved
      either by Hoechst fluorescence or by immunohistochemistry for detection of glial
      fibrillary acidic protein (GFAP) and vimentin. Grafted astrocytes expressing
      green fluorescent protein (GFP) were found both at the injection and transection
      sites. Genetically modified astrocytes thus survived, integrated, and migrated
      within the host parenchyma when grafted into the completely transected rat spinal
      cord. In addition, they retained some ability to express the GFP transgene for at
      least 6 weeks after transplantation. Adult astrocytes infected with lentiviral
      vectors can therefore be a valuable tool for the delivery of therapeutic factors
      into the lesioned spinal cord.

PMID- 16294336
TI  - Differential effects of glial cell line-derived neurotrophic factor and neurturin
      in RET/GFRalpha1-expressing cells.
AB  - The c-ret protooncogene, RET, encodes a receptor tyrosine kinase. RET is
      activated by members of the glial cell line-derived neurotrophic factor (GDNF)
      family of ligands, which include GDNF, neurturin, artemin, and persephin. The
      ligands bind RET through GDNF family receptor alpha, termed GFRalpha1-4. Despite
      the importance of RET signaling in the development of the enteric nervous system
      and the kidney, the differential signaling mechanisms between RET ligands are
      poorly established. It has been suggested that signal specificity is achieved
      through binding of the ligand to its preferred GFRalpha. To compare the signaling
      profiles of GDNF and neurturin, we have identified a cell line, NG108-15, which
      endogenously expresses RET and GFRalpha1 but not GFRalpha2-4. Immunoblot data
      showed that GDNF caused a transient activation, whereas neurturin caused a
      sustained activation, of both p44/p42 MAP kinases and PLCgamma. Under serum
      starvation, NG108-15 cells differentiate and form neurites. Neurturin but not
      GDNF stimulated neurite outgrowth, which could be blocked by the selective PLC
      inhibitor U73122. On the other hand, GDNF but not neurturin promoted cell
      survival, and this could be blocked by the p44/p42 MAP kinase inhibitor PD98059.
      Our findings not only show the differential signaling of GDNF and neurturin but
      also suggest that this can be achieved through binding to the same GFRalpha
      subtype, leading to distinct biological responses.

PMID- 16294337
TI  - Comparative sequence and structure analysis reveal features of cold adaptation of
      an enzyme in the thermolysin family.
AB  - Knowledge about the structural features underlying cold adaptation is important
      for designing enzymes of different industrial relevance. Vibriolysin from
      Antarctic bacterium strain 643 (VAB) is at present the only enzyme of the
      thermolysin family from an organism that thrive in extremely cold climate. In
      this study comparative sequence-structure analysis and molecular dynamics (MD)
      simulations were used to reveal the molecular features of cold adaptation of VAB.
      Amino acid sequence analysis of 44 thermolysin enzymes showed that VAB compared
      to the other enzymes has: (1) fewer arginines, (2) a lower Arg/(Lys + Arg) ratio,
      (3) a lower fraction of large aliphatic side chains, expressed by the (Ile +
      Leu)/(Ile + Leu + Val) ratio, (4) more methionines, (5) more serines, and (6)
      more of the thermolabile amino acid asparagine. A model of the catalytic domain
      of VAB was constructed based on homology with pseudolysin. MD simulations for 3
      ns of VAB, pseudolysin, and thermolysin supported the assumption that cold
      adapted enzymes have a more flexible three-dimensional (3D) structure than their
      thermophilic and mesophilic counterparts, especially in some loop regions. The
      structural analysis indicated that VAB has fewer intramolecular cation-pi
      electron interactions and fewer hydrogen bonds than its mesophilic (pseudolysin)
      and thermophilic (thermolysin) counterparts. Lysine is the dominating cationic
      amino acids involved in salt bridges in VAB, while arginine is dominating in
      thermolysin and pseudolysin. VAB has a greater volume of inaccessible cavities
      than pseudolysin and thermolysin. The electrostatic potentials on the surface of
      the catalytic domain were also more negative for VAB than for thermolysin and
      pseudolysin. Thus, the MD simulations, the structural patterns, and the amino
      acid composition of VAB relative to other enzymes of the thermolysin family
      suggest that VAB possesses the biophysical properties generally following
      adaptation to cold climate.

PMID- 16294338
TI  - Misfolding of the amyloid beta-protein: a molecular dynamics study.
AB  - Amyloid beta-proteins spontaneously aggregate and build plaques in the brains of
      Alzheimer's disease patients. The polypeptide has been the subject of extensive
      in vitro and computational research. Still, the pathway to aggregational forms
      and their exact conformations remain largely unclear. Here we present an
      extensive molecular dynamics approach simulating the protein in various
      temperatures, pH conditions, and with different charge states of the N- and C
      termini, thus exploring the conformational space of the protein at large. Our
      results show that the protein is able to sample different conformations, many of
      which are rich in beta structure content, and all characterized by a rapid loss
      of helix 1 that converts into a pi-helix, while helix 2 samples random and beta
      rich structures. Moreover, a hydrophobic cluster is observed involving Val18,
      Phe19, Ala21, and Gly25. The results are carefully compared with recent NMR and
      spectroscopic data, and are in global agreement with the experimental findings.

PMID- 16294339
TI  - Optimization of multiple-sequence alignment based on multiple-structure
      alignment.
AB  - Routinely used multiple-sequence alignment methods use only sequence information.
      Consequently, they may produce inaccurate alignments. Multiple-structure
      alignment methods, on the other hand, optimize structural alignment by ignoring
      sequence information. Here, we present an optimization method that unifies
      sequence and structure information. The alignment score is based on standard
      amino acid substitution probabilities combined with newly computed three
      dimensional structure alignment probabilities. The advantage of our alignment
      scheme is in its ability to produce more accurate multiple alignments. We
      demonstrate the usefulness of the method in three applications: 1) computing more
      accurate multiple-sequence alignments, 2) analyzing protein conformational
      changes, and 3) computation of amino acid structure-sequence conservation with
      application to protein-protein docking prediction. The method is available at
      http://bioinfo3d.cs.tau.ac.il/staccato/.

PMID- 16294340
TI  - A chemogenomic analysis of the transmembrane binding cavity of human G-protein
      coupled receptors.
AB  - The amino acid sequences of 369 human nonolfactory G-protein-coupled receptors
      (GPCRs) have been aligned at the seven transmembrane domain (TM) and used to
      extract the nature of 30 critical residues supposed--from the X-ray structure of
      bovine rhodopsin bound to retinal--to line the TM binding cavity of ground-state
      receptors. Interestingly, the clustering of human GPCRs from these 30 residues
      mirrors the recently described phylogenetic tree of full-sequence human GPCRs
      (Fredriksson et al., Mol Pharmacol 2003;63:1256-1272) with few exceptions. A TM
      cavity could be found for all investigated GPCRs with physicochemical properties
      matching that of their cognate ligands. The current approach allows a very fast
      comparison of most human GPCRs from the focused perspective of the predicted TM
      cavity and permits to easily detect key residues that drive ligand selectivity or
      promiscuity.

PMID- 16294341
TI  - Pressure effect on the stability and the conformational dynamics of the D
      Galactose/D-Glucose-binding protein from Escherichia coli.
AB  - The effect of the pressure on the structure and stability of the D-Galactose/D
      Glucose binding protein (GGBP) from Escherichia coli was studied by steady-state
      and time-resolved fluorescence spectroscopy, and the ability of glucose ligand to
      stabilize the GGBP structure was also investigated. Steady-state fluorescence
      experiments showed a marked quenching of fluorescence emission of GGBP in the
      absence of glucose. Instead, the presence of glucose seems to stabilize the
      structure of GGBP at low and moderate pressure values. Time-resolved fluorescence
      measurements showed that the GGBP taumean in the absence of glucose varies
      significantly up to 600 bar, while in the presence of the ligand it is almost
      unaffected by pressure increase up to 600 bar. The effect of the pressure on GGBP
      was also studied by molecular dynamics simulations. The simulation data support
      the spectroscopic results and confirm that the presence of glucose is able to
      contrast the negative effects of pressure on the protein structure. Taken
      together, the spectroscopic and computer simulation studies suggest that at
      pressure values up to 2000 bar the structure of GGBP in the absence of glucose
      remains folded, but a significant perturbation of the protein secondary
      structures can be detected. The binding of glucose reduces the negative effect of
      pressure on protein structure and confers protection from perturbation especially
      at moderate pressure values.

PMID- 16294343
TI  - Pilot intervention to enhance sexual rehabilitation for couples after treatment
      for localized prostate carcinoma.
AB  - BACKGROUND: The majority of prostate carcinoma survivors experience enduring
      sexual difficulties and associated distress in the years after definitive
      treatment. A counseling intervention aimed at improving levels of sexual
      satisfaction and increasing successful utilization of medical treatment for
      erectile dysfunction (ED) was developed and pilot-tested for both the survivor of
      prostate carcinoma and his partner. METHODS: All male participants were 3-month
      to 5-year survivors of localized prostate carcinoma who had been treated with
      radical prostatectomy or radiation therapy, and were married or in a committed
      relationship. Couples were randomized to attend four sessions of counseling
      together or to have the man attend alone. In both groups, partners completed
      behavioral homework. The sessions included education on prostate carcinoma and
      sexual function and options to treat ED as well as sexual communication and
      stimulation skills. Standardized questionnaires at baseline, posttreatment, and
      at 3-month and 6-month follow-up assessed sexual function, marital adjustment,
      psychologic distress, and utilization of treatments for ED. RESULTS: Fifty-one of
      84 couples randomized to treatment completed the intervention (61%). Attendance
      by the partner did not affect outcomes. Participants completing the intervention
      demonstrated improvement in male overall distress (P < 0.01), male global sexual
      function (P < 0.0001), and female global sexual function (P < 0.05) at 3-month
      follow-up, but regression toward baseline was noted at 6-month follow-up.
      However, utilization of ED treatments increased from 31% at the time of study
      entry to 49% at the 6-month follow-up (P = 0.003). CONCLUSIONS: The results of
      this brief pilot counseling intervention demonstrated significant gains in sexual
      function and satisfaction and increased utilization of treatments for ED.
      However, modifications are needed in future randomized trials to reduce the rate
      of premature termination and to improve long-term maintenance of gains.

PMID- 16294344
TI  - Phase II study of weekly irinotecan plus capecitabine for chemotherapy-naive
      patients with advanced nonsmall cell lung carcinoma.
AB  - BACKGROUND: A Phase II study was conducted to evaluate the efficacy and toxicity
      of an irinotecan plus capecitabine combination, a new nonplatinum regimen, in
      chemonaive patients with advanced nonsmall cell lung carcinoma (NSCLC). METHODS:
      Between July 2003 and April 2004, 53 patients with a histologically confirmed
      diagnosis of NSCLC were enrolled. All but 5 patients were male, 52 (98%) had an
      Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, 39
      (74%) had AJCC Stage IV disease, and the median age was 61 years. Treatment
      consisted of intravenous irinotecan at a dose of 90 mg/m(2) on Days 1 and 8 and
      oral capecitabine at a dose of 1000 mg/m(2) twice daily on Days 1-14 of each 21
      day cycle, given up to 12 cycles. RESULTS: Of 53 patients enrolled, 22 achieved
      objective tumor responses (all partial responses) for an overall response rate of
      41.5% (95% confidence interval [95% CI], 28.2-54.8%). After a median follow-up of
      17.4 months, the median survival was 14.6 months with a 1-year survival rate of
      60.1% (95% CI, 46.9-73.4%) and a median progression-free survival of 5.1 months.
      Treatment was very well tolerated, with only 10% of patients experiencing NCI-CTC
      Grade 3 or 4 toxicities. The most common toxicities were hand-foot syndrome and
      diarrhea. In multiple logistic regression analysis for overall response, only the
      stage predicted for significantly better response (P = 0.04). Squamous cell
      carcinoma was marginally predictive for better response (P = 0.08). CONCLUSIONS:
      The irinotecan plus capecitabine regimen demonstrated an antitumor activity that
      is favorably comparable with other commonly used cisplatin-based regimens. Given
      the mild toxicity profile and favorable survival outcome, this nonplatinum
      regimen warrants further evaluation in a randomized trial.

PMID- 16294346
TI  - Capecitabine combined with gemcitabine (CapGem) as first-line treatment in
      patients with advanced/metastatic biliary tract carcinoma.
AB  - BACKGROUND: Biliary tract carcinoma is an aggressive cancer, with median survival
      rarely exceeding 6 months. There is currently no established palliative standard
      of care. A Phase II trial was conducted to study a combination of oral
      capecitabine and gemcitabine (CapGem) as first-line therapy in patients with
      advanced and/or metastatic biliary carcinoma. METHODS: Patients with unresectable
      or metastatic intrahepatic or extrahepatic biliary duct carcinoma and gallbladder
      carcinoma were enrolled. Eligible patients had histologically or cytologically
      confirmed, measurable adenocarcinoma and had not received prior therapy with
      capecitabine or gemcitabine. Treatment consisted of intravenous (i.v.)
      gemcitabine (1000 mg/m(2) on Days 1 and 8) plus oral capecitabine (650 mg/m(2)
      twice daily on Days 1-14) every 3 weeks for up to 6 cycles. Tumor response,
      survival, and safety were determined. RESULTS: A total of 44 patients were
      evaluable. Primary tumor sites were: intrahepatic (n = 14) and extrahepatic
      biliary duct (n = 16); gallbladder (n = 7); and ampulla (n = 7). Fourteen (32%)
      patients had a partial response and 15 (34%) patients had stable disease. Median
      time to disease progression and overall survival were 6.0 (range, 3.8-8.1) and 14
      (range, 11.4-16.6) months, respectively. The 1-year survival rate was 58%. No
      Grade 4 adverse events were seen. Transient Grade 3 neutropenia/thrombocytopenia
      and manageable (almost invariably Grade 2) nausea, diarrhea, and hand-foot
      syndrome were the most common adverse events. CONCLUSIONS: CapGem is an active
      and well tolerated first-line combination chemotherapy regimen for patients with
      advanced/metastatic biliary tract carcinoma that offers a convenient home-based
      therapy.

PMID- 16294345
TI  - Clinical trial of valproic acid and all-trans retinoic acid in patients with poor
      risk acute myeloid leukemia.
AB  - BACKGROUND: Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, induced
      in vitro differentiation of primary acute myeloid leukemia (AML) blasts, an
      effect enhanced by all-trans retinoic acid (ATRA). Clinical responses to VPA were
      recently observed in patients with myelodysplastic syndrome (MDS). Herein, the
      authors have described results of a clinical trial with VPA plus ATRA in 26
      patients with poor-risk AML. METHODS: VPA (5-10 mg/kg starting dose) and ATRA (45
      mg/m(2)) were administered orally. Low-dose AraC or hydroxyurea were permitted to
      control leukocytosis. Biologic activity of VPA was confirmed by serial analysis
      of HDAC2 protein levels in peripheral blood (PB) mononuclear cells. RESULTS:
      Nineteen of 26 patients completed at least 4 weeks of VPA/ATRA treatment; 7
      patients were withdrawn prematurely because of rapidly progressive disease (n =
      3) or unacceptable neurologic and cardiovascular toxicity (n = 4). Additional
      cytoreductive treatment was required in 58% of patients enrolled. Median
      treatment duration was 3 months. No patient achieved complete remission, one with
      de novo AML had a minor response, and two patients with secondary AML arising
      from myeloproliferative disorder (MPD) achieved a partial remission and clearance
      of PB blasts, respectively. The latter responses were accompanied by profound
      granulocytosis and erythrocytosis in both patients, reminiscent of the response
      pattern known from ATRA treatment of acute promyelocytic leukemia. However,
      cytogenetic analysis of isolated CD34(+) cells and granulocytes did not reveal
      terminal differentiation of leukemic blasts. CONCLUSIONS: Treatment with VPA/ATRA
      results in transient disease control in a subset of patients with AML that has
      evolved from a myeloproliferative disorder but not in patients with a primary or
      MDS-related AML.

PMID- 16294347
TI  - Synthesis of donor-acceptor alkynylcyclopropanes by diastereoselective
      cyclopropanation of electron-deficient alkenes with alkoxyalkynyl Fischer carbene
      complexes.
AB  - The reaction of electron-deficient alkenes with alkoxyalkynyl Fischer carbene
      complexes (FCCs) represents a straightforward route to a new type of captodative
      (donor-acceptor) alkynylcyclopropanes, which have been prepared in moderate to
      high yields and in a diastereoselective manner. Some studies regarding the
      employment of additives to facilitate the recovery of the metal moiety after the
      reaction are also described. Finally, the first example of a cyclopropanation
      reaction through employing Fischer carbene complexes under microwave irradiation
      is presented; this method proved to be an advantageous alternative to the thermal
      reaction.

PMID- 16294348
TI  - Water-soluble fluorescent boronic acid compounds for saccharide sensing:
      substituent effects on their fluorescence properties.
AB  - Four new naphthalene-based boronic acid compounds (1-4) were synthesized. The
      effect of various carbohydrates on their fluorescence properties has been studied
      in aqueous phosphate buffer at pH 7.4. Different substitutions on the aniline
      group of the naphthalene ring resulted in significant differences in fluorescence
      properties for these four compounds. Compound 1 shows ratiometric fluorescence
      changes upon addition of a sugar. Compounds 2 and 3 do not show ratiometric
      fluorescence changes but show very large fluorescence intensity changes (about 70
      fold fluorescence intensity increase). In addition to the quantifiable
      fluorescence property changes upon sugar addition, the fluorescence color changes
      of 1-3 are also visible to the naked eye. However, amidation of the aniline
      nitrogen atom significantly diminishes the fluorescence intensity of compound 4.
      The crystal structure of one boronic acid provided some insight into the
      structural features that are important for the fluorescence properties of these
      compounds.

PMID- 16294349
TI  - A photocontrolled beta-hairpin peptide.
AB  - Beta-hairpins constitute the smallest beta-type structures in peptides and
      proteins. The development of highly stable, yet monomeric beta-hairpins based on
      the tryptophan zipper motif was therefore a remarkable success [A. G. Cochran, N.
      J. Skelton, M. A. Starovasnik, Proc. Natl. Acad. Sci USA 2001, 98, 5578-5583]. We
      have been able to design, synthesize and characterize a hairpin based on this
      motif which incorporates an azobenzene-based photoswitch, that allows for time
      resolved folding studies of beta-structures with unprecedented time resolution.
      At room temperature the trans-azo isomer exhibits a mostly disordered structure;
      however, light-induced isomerization to the cis-azo form leads to a predominantly
      extended and parallel conformation of the two peptide parts, which are linked by
      the novel photoswitch, [3-(3-aminomethyl)phenylazo]phenylacetic acid (AMPP).
      While in the original sequence the dipeptide Asn-Gly forms a type I' beta-turn
      which connects the two strands of the hairpin, this role is adopted by the AMPP
      chromophore in our photoresponsive beta-hairpin that can apparently act as a beta
      I'-turn mimetic. The beta-hairpin structure was determined and confirmed by NMR
      spectroscopy, but the folding process can be monitored by pronounced changes in
      the CD, IR and fluorescence spectra. Finally, incorporation of the structurally
      and functionally important beta-hairpin motif into proteins by chemical ligation
      might allow for the photocontrol of protein structures and/or functions.

PMID- 16294350
TI  - Inherent complexities of trace detection by surface-enhanced Raman scattering.
AB  - Surface-enhanced Raman scattering (SERS) and surface-enhanced resonance Raman
      scattering (SERRS) are powerful optical scattering techniques used in such
      frontier areas of research as ultrasensitive chemical analysis, the
      characterization of nanostructures, and the detection of single molecules.
      However, measuring and, most importantly, interpreting SERS/SERRS spectra can be
      incredibly challenging. This is the result of modifications to the measured
      spectra that are due to of a variety of instabilities and contributions. These
      interferences and modifications arise from the nature of the enhancement itself,
      as well as the conditions used to attain SERS spectra. The present report is an
      attempt to collect in one place the analytical interferences that are most
      commonly found during the collection of SERS/SERRS spectra.

PMID- 16294351
TI  - Aromaticity analysis of lithium cation/pi complexes of aromatic systems.
AB  - The changes in the local aromaticity of aromatic rings on complexation with
      lithium cation are discussed for a series of polycyclic aromatic hydrocarbons by
      using, as probes of aromaticity, the para-delocalization index (PDI), the
      aromatic fluctuation index (FLU), the harmonic oscillator model of aromaticity
      index (HOMA), and the nucleus-independent chemical shift (NICS). In most cases,
      changes in the electronically based PDI and FLU indices are almost irrelevant.
      For this reason, the analysis is carried out mainly with the more sensitive HOMA
      and NICS descriptors. These indices indicate that changes in the local aromatic
      character of the different rings are small. In general, Li+ interacts more
      favorably with the ring having the largest pi charge, but there is no correlation
      between these magnitudes. The ring directly interacting with the lithium cation
      suffers a slight but significant reduction of aromaticity, while the reduction of
      the local aromaticity of the adjacent rings is minor. For those rings located
      further away from the ring directly connected to Li+, we found generally a small
      increase in aromaticity. Although there is no clear correlation between
      aromaticity and Li+ binding enthalpies, there is a rough correlation between the
      latter and the change in the aromaticity of the ring directly interacting with
      the metal cation.

PMID- 16294352
TI  - Influence of coadsorbates on the NO dissociation on a rhodium(311) surface.
AB  - Density functional theory (DFT) studies were performed to investigate the
      influence of coadsorbates on the nitrogen oxide dissociation on the vicinal
      rhodium(311) surface. This study amplifies prior studies on the dissociation of
      oxygen and nitrogen oxide on the (111) facet of rhodium. The influence of
      coadsorbates on the kinetic parameters and thermochemistry of the NO dissociation
      on Rh311 was studied. In addition, the activation energy and thermochemistry of
      this reaction were determined as a function of oxygen preoccupation/initial
      coverage. Steric and electronic effects and their influence on the dissociation
      reaction were examined. The results are discussed in the face of an NOx
      dissociation catalyst system proposed by Nakatsuji.

PMID- 16294353
TI  - Probing the water coordination of protein-targeted MRI contrast agents by pulsed
      ENDOR spectroscopy.
AB  - A novel methodology based on electron-nuclear double resonance (ENDOR)
      spectroscopy is used for the direct determination of the water coordination
      number (q) of gadolinium-based magnetic resonance imaging (MRI) contrast agents.
      Proton ENDOR spectra can be obtained at approximately physiological
      concentrations for metal complexes in frozen aqueous solutions either in the
      presence or absence of protein targets. It is shown that, depending on the
      structure of the co-ligand, the water hydration number of a complex in aqueous
      solution can be significantly different to when the complex is noncovalently
      bound to a protein. From the ENDOR spectra of the exchangeable protons, precise
      information on the metal-proton distance can be derived as well. These essential
      parameters directly correlate with the efficacy of MRI contrast agents and should
      therefore aid the development of novel, highly efficient compounds targeted to
      various proteins.

PMID- 16294354
TI  - New catanionic triblock amphiphiles: supramolecular organization of a sugar
      derived bolaamphiphile associated with dicarboxylates.

PMID- 16294355
TI  - Chemical synthesis and optical properties of size-selected CdSe tetrapod-shaped
      nanocrystals.

PMID- 16294356
TI  - Facile synthesis and optimization of conductive copolymer nanoparticles and
      nanocomposite films from aniline with sulfodiphenylamine.
AB  - A new series of electrically conductive pure copolymer nanoparticles was facilely
      synthesized by using oxidative polymerization of aniline (AN) and sodium
      diphenylamine-4-sulfonate (SDP) in acidic media in the absence of stabilizer. The
      variation of the structure of the copolymer particles was comprehensively studied
      by carefully choosing several important parameters, such as the comonomer ratio,
      oxidant/monomer ratio, polymerization time and temperature, monomer
      concentration, acidic medium, and oxidant species. Analytical techniques used
      include IR and UV-visible spectroscopy, X-ray diffraction, laser particle
      analysis, atomic force microscopy, and transmission electron microscopy. It was
      found that the particle size varied significantly with the above-mentioned
      polymerization parameters, only changes in the salt concentration in the aqueous
      testing solution had no noticeable effect. The polymerization conditions were
      optimized for the formation of copolymer nanoparticles with sought-after
      properties. The doped copolymer particles of AN/SDP (50:50) at an oxidant/monomer
      molar ratio of 0.5 exhibit a minimum length of 50 nm and a minimum diameter of 44
      nm. The bulk electrical conductivity of the copolymer particles increases greatly
      from 5.90x10(-4) to 1.15x10(-2) S cm(-1) with increasing AN content. Compared
      with barely soluble polyaniline, the copolymers exhibit a remarkably enhanced
      solubility in most solvents, including NH4OH and even water, due to the presence
      of the hydrophilic sulfonic groups. Nanocomposite films of the nanoparticles and
      cellulose diacetate exhibit a percolation threshold of down to 0.1 wt %, at which
      the film retains 98% of the transparency, 94% of the strength, and 5x10(7) times
      the conductivity of a pure cellulose diacetate film.

PMID- 16294357
TI  - New insights into the mechanism of proton transfer to hydride complexes: kinetic
      and theoretical evidence showing the existence of competitive pathways for
      protonation of the cluster [W3S4H3(dmpe)3]+ with acids.
AB  - The reaction of the hydride cluster [W3S4H3(dmpe)3]+ (1, dmpe = 1,2
      bis(dimethylphosphanyl)ethane) with acids (HCl, CF3COOH, HBF4) in CH2Cl2 solution
      under pseudo-first-order conditions of excess acid occurs with three kinetically
      distinguishable steps that can be interpreted as corresponding to successive
      formal substitution processes of the coordinated hydrides by the anion of the
      acid (HCl, CF3COOH) or the solvent (HBF4). Whereas the rate law for the third
      step changes with the nature of the acid, the first two kinetic steps always show
      a second-order dependence on acid concentration. In contrast, a single kinetic
      step with a first-order dependence with respect to the acid is observed when the
      experiments are carried out with a deficit of acid. The decrease in the T1 values
      for the hydride NMR signal of 1 in the presence of added HCl suggests the
      formation of an adduct with a W-H...H-Cl dihydrogen bond. Theoretical
      calculations for the reaction with HCl indicate that the kinetic results in
      CH2Cl2 solution can be interpreted on the basis of a mechanism with two
      competitive pathways. One of the pathways consists of direct proton transfer
      within the W-H...H-Cl adduct to form W-Cl and H2, whereas the other requires the
      presence of a second HCl molecule to form a W-H...H-Cl...H-Cl adduct that
      transforms into W-Cl, H2 and HCl in the rate-determining step. The activation
      barriers and the structures of the transition states for both pathways were also
      calculated, and the results indicate that both pathways can be competitive and
      that the transition states can be described in both cases as a dihydrogen complex
      hydrogen-bonded to Cl- or HCl2(-).

PMID- 16294358
TI  - Binding of cationic and neutral phenanthridine intercalators to a DNA oligomer is
      controlled by dispersion energy: quantum chemical calculations and molecular
      mechanics simulations.
AB  - Correlated ab initio as well as semiempirical quantum chemical calculations and
      molecular dynamics simulations were used to study the intercalation of cationic
      ethidium, cationic 5-ethyl-6-phenylphenanthridinium and uncharged 3,8-diamino-6
      phenylphenanthridine to DNA. The stabilization energy of the cationic
      intercalators is considerably larger than that of the uncharged one. The dominant
      energy contribution with all intercalators is represented by dispersion energy.
      In the case of the cationic intercalators, the electrostatic and charge-transfer
      terms are also important. The DeltaG of ethidium intercalation to DNA was
      estimated at -4.5 kcal mol(-1) and this value agrees well with the experimental
      result. Of six contributions to the final free energy, the interaction energy
      value is crucial. The intercalation process is governed by the non-covalent
      stacking (including charge-transfer) interaction while the hydrogen bonding
      between the ethidium amino groups and the DNA backbone is less important. This is
      confirmed by the evaluation of the interaction energy as well as by the
      calculation of the free energy change. The intercalation affects the macroscopic
      properties of DNA in terms of its flexibility. This explains the easier entry of
      another intercalator molecule in the vicinity of an existing intercalation site.

PMID- 16294359
TI  - Density functional studies of dicobalt octacarbonyl-mediated azobenzene formation
      from 4-ethynylaniline.
AB  - Two adiabatic potential-energy surfaces are employed for probing the processes of
      [Co2(CO)8]-mediated C6H5N=NC6H5 formation from NH2C6H5. Elementary steps,
      including oxidative addition of the coordinated amine proton to the cobalt
      center, reductive elimination of H2, CO association, and the coupling process of
      the diamino fragments, are modeled and examined by using DFT methods at the B3
      LYP/631 LAN level. The formation of C6H5N=NC6H5 from NH2C6H5 through reductive
      coupling is a thermodynamically unfavorable process. Three hydride-migration
      processes, from the proton of N-H to the cobalt center, are established as the
      most energy-demanding steps. The activation energies (deltaG*) are calculated as
      49.4, 55.4, and 33.3 kcal mol(-1), respectively, for the proposed reaction route
      1. These large activation energies might be reduced slightly by purposely adding
      small protic molecules, such as H2O, or by changing the active metal from Co to a
      heavier metal, such as Rh or Ir. An alternative pathway, route 2, is also
      proposed, in which transition states with four-membered rings are formed. By this
      route, severe strain caused by the formation of three-membered rings during the
      hydride-migration processes in route 1 can be avoided. Route 2 is established as
      the more energy-feasible reaction pathway.

PMID- 16294360
TI  - Solid-phase synthesis and biological activity of a combinatorial cross-conjugated
      dienone library.
AB  - The solid-phase synthesis of a combinatorial cross-conjugated dienone library
      based on the structure of clavulones and their biological activity are reported.
      Clavulones are a family of marine prostanoids, and are composed of a cross
      conjugated dienone system bearing two alkyl side-chains. The cross-conjugated
      dienone system irreversibly reacted with two nucleophiles. Our strategy for the
      solid-phase synthesis of the cross-conjugated dienones involves the Sonogashira
      coupling reaction of a solid-supported cyclopentenone 10 bearing an acetylene
      group, followed by aldol condensation with aldehydes. The diphenyl derivative 7
      aA was prepared from the solid-supported cyclopentenone 10 in 56% total yield.
      Combinatorial synthesis of a small library using twelve halides and eight
      aldehydes resulted in the production of 74 desired compounds from 98 candidates,
      and were detected by their mass spectra. Antiproliferative effects of the crude
      compounds against HeLaS3 cells showed that eleven samples showed strong antitumor
      activity (IC50<0.05 microM). Further biological examination of four purified
      compounds by using five tumor cell lines (A549, HeLaS3, MCF7, TMF1, and P388)
      revealed strong cytotoxicity comparable to that of adriamycin.

PMID- 16294361
TI  - Synthesis of strained tricyclic beta-lactams by intramolecular [2+2]
      cycloaddition reactions of 2-azetidinone-tethered enallenols: control of
      regioselectivity by selective alkene substitution.
AB  - A convenient metal-free methodology for the preparation of structurally novel,
      strained tricyclic beta-lactams containing a cyclobutane ring has been developed.
      The first examples accounting for the intramolecular [2+2] cycloaddition
      reactions in beta-lactams have been achieved by the thermolysis of 2-azetidinone
      tethered enallenols, which have been prepared in aqueous media by regio- and
      diastereoselective indium-mediated carbonyl allenylation of 4-oxoazetidine-2
      carbaldehydes. Notably, the regioselectivity of the cycloaddition can be tuned in
      the allene component just by a subtle variation in the substitution pattern of
      the alkene component.

PMID- 16294362
TI  - Unprecedented stereoselective synthesis of catalytically active chiral Mo3CuS4
      clusters.
AB  - Cluster excision of polymeric {Mo3S7Cl4}n phases with chiral phosphane (+)-1,2
      bis[(2R,5R)-2,5-(dimethylphospholan-1-yl)]ethane ((R,R)-Me-BPE) or with its
      enantiomer ((S,S)-Me-BPE) yields the stereoselective formation of the trinuclear
      cluster complexes [Mo3S4{(R,R)-Me-BPE}3Cl3]+ ([(P)-1]+) and [Mo3S4{(S,S)-Me
      BPE}3Cl3]+ ([(M)-1]+), respectively. These complexes possess an incomplete
      cuboidal structure with the metal atoms defining an equilateral triangle and one
      capping and three bridging sulfur atoms. The P and M symbols refer to the
      rotation of the chlorine atoms around the C3 axis, with the capping sulphur atom
      pointing towards the viewer. Incorporation of copper into these trinuclear
      complexes affords heterodimetallic cubane-type compounds of formula
      [Mo3CuS4{(R,R)-Me-BPE}3Cl4]+ ([(P)-2]+) or [Mo3CuS4{(S,S)-Me-BPE}3Cl4]+ ([(M)
      2]+), respectively, for which the chirality of the trinuclear precursor is
      preserved in the final product. Cationic complexes [(P)-1]+, [(M)-1]+, [(P)-2]+,
      and [(M)-2]+ combine the chirality of the metal cluster framework with that of
      the optically active diphosphane ligands. The known racemic [Mo3CuS4(dmpe)3Cl4]+
      cluster (dmpe = 1,2-bis(dimethylphosphanyl)ethane) as well as the new
      enantiomerically pure Mo3CuS4 [(P)-2]+ and [(M)-2]+ complexes are efficient
      catalysts for the intramolecular cyclopropanation of 1-diazo-5-hexen-2-one (3)
      and for the intermolecular cyclopropanation of alkenes, such as styrene and 2
      phenylpropene, with ethyl diazoacetate. In all cases, the cyclopropanation
      products were obtained in high yields. The diastereoselectivity in the
      intermolecular cyclopropanation of the alkenes and the enantioselectivity in the
      inter- or intramolecular processes are only moderate.

PMID- 16294363
TI  - FDA drug prescribing warnings: is the black box half empty or half full?
AB  - PURPOSE: Black box warnings (BBWs) are the Food and Drug Administration's (FDA)
      strongest labeling requirements for high-risk medicines. It is unknown how
      frequently physicians prescribe BBW drugs and whether they do so in compliance
      with the warnings. The purpose of the present study was to assess the frequency
      of use of BBW medications in ambulatory care and prescribing compliance with BBW
      recommendations. METHODS: This retrospective study used automated claims data of
      929 958 enrollees in 10 geographically diverse health plans in the United States
      to estimate frequency of use in ambulatory care of 216 BBW drugs/drug groups
      between 1/1/99 and 31/6/01. We assessed dispensing compliance with the BBW
      requirements for selected drugs. RESULTS: During a 30-month period, more than 40%
      of enrollees received at least one medication that carried a BBW that could
      potentially apply to them. We found few instances of prescribing during pregnancy
      of BBW drugs absolutely contra-indicated in pregnancy. There was almost no co
      prescribing of contra-indicated drugs with the two QT-interval-prolonging BBW
      drugs evaluated. Most non-compliance occurred with recommendations for baseline
      laboratory monitoring (49.6% of all therapy initiations that should have been
      accompanied by baseline laboratory monitoring were not). CONCLUSIONS: Many
      individuals receive drugs considered to carry the potential for serious risk. For
      some of these drugs, use is largely consistent with their BBW, while for others
      it is not. Since it will not be possible to avoid certain drug- associated risks,
      it will be important to develop effective methods to use BBWs and other methods
      to minimize risks.

PMID- 16294364
TI  - Estimates of acetaminophen (Paracetomal)-associated overdoses in the United
      States.
AB  - OBJECTIVE: To estimate the number of acetaminophen-associated overdoses in the
      United States and identify possible risk factors for intervention. METHODS: The
      investigators obtained estimates of acetaminophen-associated overdoses using
      different national databases. Two emergency room databases, a hospital discharge
      database, a national mortality file, and a poison surveillance database were used
      to identify cases. The FDA's spontaneous reporting system was searched to
      identify possible root causes for overdoses. RESULTS: Analysis of national
      databases show that acetaminophen-associated overdoses account for about 56,000
      emergency room visits and 26,000 hospitalizations yearly. Analysis of national
      mortality files shows 458 deaths occur each year from acetaminophen-associated
      overdoses; 100 of these are unintentional. The poison surveillance database
      showed near-doubling in the number of fatalities associated with acetaminophen
      from 98 in 1997 to 173 in 2001. AERS data describe a number of possible causes
      for unintentional acetaminophen-associated overdoses. CONCLUSIONS: Each year a
      substantial numbers of Americans experience intentional and unintentional
      acetaminophen-associated overdoses that, in severe cases, lead to serious illness
      and possible death. This summary of a series of analyses highlights the need for
      strategies to reduce this public health burden.

PMID- 16294365
TI  - Using a pharmaco-epidemiological approach to estimate diabetes type 2 prevalence
      in Portugal.
AB  - PURPOSE: To estimate the prevalence of drug-treated diabetes type 2 in Portugal
      using drug consumption data and accounting for the proportion of patients treated
      with combinations of oral hypoglycaemic agents (OHAs). METHODS: The prevalence of
      diabetes treated by OHAs was calculated on the basis of: IMS-Health data for
      Portugal (2003) and two measures of daily drug intake-defined daily dose (DDD)
      and prescribed daily dose (PDD), after correcting for the proportion of patients
      treated with two or more OHAs. The PDD and proportion of patients in combination
      therapies have been obtained in a descriptive, cross-sectional national survey,
      conducted in 2003, by inquiry of 1,046 type 2 diabetics country wide distributed.
      RESULTS: Drug use study: We have studied 1046 type 2 diabetics (539 women, 501
      men, 6 sex unknown), with a mean age of 64.5 (SD=11) years. OHAs were prescribed
      as monotherapy in 46.8% (489/1,046) of the patients and the remaining 557 (53.2%)
      received from 2 to 4 OHAs concomitantly.Diabetes prevalence: Using DDD as the
      mean daily intake consumption unit, the prevalence of drug-treated type 2
      diabetes was 4.15%, which dropped to 2.52% when the proportion of OHAs
      associations was taken into account. Using PDD these values were 4.48% and 2.72%,
      respectively. CONCLUSIONS: Since a high proportion of patients are treated with
      combination of OHAs in clinical practice, it is imperative to account for that
      confounder in order to improve the accuracy of estimate from drug consumption
      data. The use of this methodology provided a slight under-estimation of diabetes
      prevalence, compared with the National Health Authorities values (3%-5%).
      Nevertheless we consider this as an efficient tool to estimate drug-treated
      diabetes prevalence that should be implemented in a regular way for longitudinal
      observations, in order to generate signals.

PMID- 16294366
TI  - The impact of cytochrome P450-2D6 genotype on the use and interpretation of
      therapeutic drug monitoring in long-stay patients treated with antidepressant and
      antipsychotic drugs in daily psychiatric practice.
AB  - PURPOSE: This retrospective follow-up study investigates whether cytochrome P450
      2D6 (CYP2D6) genotype explains variability in plasma concentrations of
      psychotropic drugs in daily psychiatric practice. METHODS: The study population
      consisted of 62 hospitalised psychiatric patients genotyped for CYP2D6. Primary
      endpoint was the normalised plasma concentration ratio which was defined as the
      [measured concentration]/[mean therapeutic concentration] allowing comparison of
      plasma concentrations of different substrates. Secondary endpoint was a plasma
      concentration above the therapeutic range. The determinant was CYP2D6 genotype
      classified as ultrarapid metaboliser (UM), extensive metaboliser (EM),
      intermediate metaboliser (IM), or poor metaboliser (PM). The relation between
      CYP2D6 genotype and the normalised plasma concentration ratio was assessed with a
      linear mixed-effects model after adjustment for the Prescribed Daily Dose (PDD).
      The risk of having a plasma concentration above the therapeutic range was
      assessed with a logistic mixed-effects model. RESULTS: For antidepressants,
      CYP2D6 genotype PM (1.68 (95%CI: 1.01-2.28)) and IM (1.09 (95%CI: 0.77-1.29))
      were associated with higher normalised plasma concentration ratios of
      antidepressants compared to EMs (0.56 (95%CI: 0.26-0.74)). In addition, the risk
      of a plasma concentration above the therapeutic range was increased for PMs (OR
      33.1 (95%CI: 2.0-544.6)) and IMs (OR 8.2 (95%CI: 1.1-60.3)) relative to EMs using
      antidepressants. CYP2D6 genotype could not clearly explain variability in plasma
      concentrations of antipsychotics possibly due to a low frequency of therapeutic
      drug monitoring (TDM) in antipsychotics primarily metabolised by CYP2D6 in daily
      psychiatric practice. CONCLUSIONS: CYP2D6 genotype contributes to clinically
      relevant variability in plasma concentrations of antidepressants but probably not
      antipsychotics in daily clinical practice.

PMID- 16294367
TI  - Spontaneous reporting of hepatotoxicity associated with antiandrogens: data from
      the Spanish pharmacovigilance system.
AB  - PURPOSE: To analyse the type and main features of the hepatotoxicity induced by
      steroidal and non-steroidal antiandrogens spontaneously reported by physicians,
      pharmacists and nurses. This analysis could increase the information related to
      these adverse reactions mainly available from the published isolated cases.
      METHODS: Using the Spanish Pharmacovigilance database we searched for spontaneous
      reports recorded since the date of approval of each antiandrogen up to the
      present time. We analysed the frequency of liver disorders, the preferred terms
      coded, the presence of other hepatotoxic drugs, and the characteristics of cases
      of hepatitis. RESULTS: Liver disorders were the most common adverse reactions
      associated with flutamide and bicalutamide, but not with cyproterone acetate.
      'Hepatitis' and 'cholestatic hepatitis' were the most frequent terms coded. In
      38% of the reports related to cyproterone acetate, 18% of those related to
      flutamide and 33% of those related to bicalutamide the patient had simultaneously
      received other hepatotoxic drugs. The disproportionality analysis of hepatitis
      showed a strong association with flutamide and a weak association with
      bicalutamide and cyproterone acetate. Mean doses of flutamide and bicalutamide
      were very close to their defined daily dose (DDD) to treat prostate cancer,
      although in the case of cyproterone acetate it was slightly higher. The latency
      period of hepatitis was between 3 and 10 months for the three antiandrogens, and
      the recovery period was shorter (0.5-3 months). The majority of the reported
      cases of hepatitis evolved favourably. CONCLUSION: Our results highlight the
      hepatotoxic potential of flutamide compared to cyproterone acetate. The data
      related to bicalutamide should be cautiously considered due to the smaller number
      of reports.

PMID- 16294368
TI  - Assessment of quality of life and relevant factors in elderly diabetic patients
      in the Shanghai community.
AB  - PURPOSE: The study was to assess the quality of life (QOL) of the elderly
      diabetes mellitus (DM) in Shanghai community and to screen the possible risk
      factors. METHODS: A total of 951 patients with elderly DM and 1007 elderly
      subjects with normal glucose tolerance from the same community as control group
      were enrolled in the study. A door-to-door retrospectively epidemiological survey
      was used to collect data of QOL, demographic, and diabetic information. The SF-36
      instrument (Chinese edition) was used to assess QOL. Multiple stepwise linear
      regression analysis was also used to identify possible risk factors of QOL in
      elder DM. RESULTS: In subjects with elderly DM, the general assessment of
      perceived health was worse, compared with the normal elderly people; the mean
      score of multi-item dimensions assessment had been decreased, the lowest and
      highest scores of which on SF-36, respectively, were general health and body pain
      (ranged from 42.08 to 77.00). Based on the multiple stepwise regression analysis,
      23 risk factors entered 9 multiple regressive models (9 dependent variables of
      which stand for the scores of 8 dimensions and the total score on SF-36) with
      different amount ultimately. Within the 13 risk factors that affect QOL of the
      elderly diabetic patients, the negative correlated factors were gender, age,
      payment ability of medical treatment, tumor, level of fasting plasma glucose
      (FPG), medicines purchasing channels, diabetic microvascular complications,
      diabetic macrovascular complications, acute complications, while the positive
      correlated factors were occupation, income, exercises, knowledge of DM. The
      multiple correlation coefficient square (R2) represented the above 13 risk
      factors had a totally 30.5% impact on the entire QOL. CONCLUSIONS: QOL of elderly
      DM population had significantly been decreased; QOL of the elderly patients in
      Shanghai community had many risk factors, which on one hand stated the complexity
      of elderly DM, and on the other hand gave us many useful and practical methods to
      improve QOL of elderly DM.

PMID- 16294369
TI  - Support and training needs of cancer support group leaders: a review.
AB  - This review focuses on the support and training needs of cancer support group
      leaders. With an increasing popularity of support groups and growing evidence of
      the crucial role of group leaders in positive patient outcomes, there is an
      imperative to identify ways of promoting these outcomes and preventing leader
      burnout, an issue contributing to the demise of some support groups. Despite
      this, there is a paucity of research in this area. Available research data
      clearly illustrates that both professional and peer support group leaders
      recognise their need for better support, training and information. One study of
      health professionals identified a need for more advanced skills involved in group
      processes and specific issues such as dealing with the death of members. Specific
      leader behaviours, in particular active intervention in group interactions and
      supportive care, have also been associated with improved patient quality of life.
      To date, there is no clear evidence as to how best to achieve and support these
      effective group leader skills. While many cancer societies and other associations
      provide introductory training and information kits about 'how to start a support
      group,' no advanced training or support interventions are available. Further
      research is needed to provide an evidence base for group leader training and to
      evaluate the impact of such training on both leader and patient outcomes.

PMID- 16294370
TI  - Hydrophilic core-shell microspheres: a suitable support for controlled attachment
      of proteins and biomedical diagnostics.
AB  - Functional hydrophilic microspheres (latex particles) have found various
      applications in life sciences and in medicine - particularly in latex diagnostic
      tests. This paper presents a comprehensive review of studies on latex particles
      with a hydrophilic interfacial layer composed of various hydrophilic polymers
      with reactive groups at the ends of macromolecules or at each monomeric unit
      along the chain. Typical examples of these hydrophilic polymers are poly(2
      hydroxyethyl methyl methacrylate), poly(acrylic acid), poly(N,N
      dimethylacrylamide), polysaccharides, poly(ethylene oxide) and polyglycidol.
      Hydrophilic microspheres with different morphologies (uniform or core-shell, see
      Figure) have been synthesized by emulsion and dispersion polymerizations. The
      chemical structure of polymers which constitute the interfacial layer of
      microspheres has been investigated using a variety of instrumental techniques
      (such as XPS, SSIMS and NMR) and analytical methods based on specific chemical
      reactions suitable for the determination of particular functional groups.
      Microspheres are exposed to contact with proteins in the majority of medical
      applications. This paper presents examples of studies on the attachment of these
      biomacromolecules to microspheres. The relation between the structure of the
      interfacial layer of microspheres and the ability of these particles for the
      covalent binding of proteins is discussed. Several examples of diagnostic tests,
      in which hydrophilic microspheres with adsorbed or covalently immobilized
      proteins were used as reagents, are presented. The paper also contains a short
      review of the application of magnetic hydrophilic particles for protein
      separation. Examples of hydrophilic latex particles used for hemoperfusion or
      heavy metal ion separation are presented. Hydrophilic microspheres with uniform
      or core-shell morphologies.

PMID- 16294371
TI  - Deregulation of the hedgehog signalling pathway: a possible role for the PTCH and
      SUFU genes in human rhabdomyoma and rhabdomyosarcoma development.
AB  - The naevoid basal cell carcinoma syndrome (NBCCS) is caused by mutations in the
      hedgehog receptor PTCH gene. It is characterized by developmental defects and a
      predisposition to the development of certain tumours, such as basal cell
      carcinoma, medulloblastoma and meningioma, and potentially fetal rhabdomyomas and
      embryonal rhabdomyosarcomas. This study aimed to analyse PTCH status in an NBCCS
      patient with fetal rhabdomyoma and to investigate whether deregulation of
      hedgehog signalling, as shown by altered expression of hedgehog pathway
      components and/or genetic imbalances, is a general finding in sporadic
      rhabdomyomas and rhabdomyosarcomas. The NBCCS patient had a novel PTCH germ-line
      mutation, 1370insT, and developed a fetal rhabdomyoma that harboured a 30 bp in
      frame deletion in the second allele resulting in homozygous inactivation of PTCH.
      Sporadic rhabdomyomas and rhabdomyosarcomas showed overexpression of PTCH (43/43)
      and GLI1 (41/43) mRNA, as determined by in situ hybridization, indicating ongoing
      active hedgehog signalling. Immunohistochemical staining revealed a subgroup of
      fetal rhabdomyomas and embryonal rhabdomyosarcomas (12/34) lacking PTCH
      immunoreactivity. Four of nine informative fetal rhabdomyomas and embryonal
      rhabdomyosarcomas showed loss of heterozygosity (LOH) in the PTCH region with two
      of these (one fetal rhabdomyoma and one embryonal rhabdomyosarcoma) also showing
      LOH in the SUFU region. These findings suggest that haploinsufficiency for the
      two tumour suppressor genes PTCH and SUFU, which are both active in the same
      signalling pathway, may be important for tumour development. Based on our results
      we propose that the pathogenesis of rhabdomyoblastic tumours, particularly fetal
      rhabdomyomas and embryonal rhabdomyosarcomas, involves deregulation of the
      hedgehog signalling pathway.

PMID- 16294372
TI  - Differential expression of oestrogen receptors in human secondary lymphoid
      tissues.
AB  - Many autoimmune diseases including rheumatoid arthritis (RA), Sjogren's syndrome
      (SS) and systemic lupus erythematosus (SLE) occur much more frequently in women
      than in men. There is much evidence that oestrogen is the major cause of this
      gender difference. Interestingly, oestrogen relieves the symptoms of RA and SS
      but it exacerbates SLE. This contradictory effect of oestrogen on autoimmune
      diseases is not well understood. Most of the effects of oestrogen are mediated by
      two receptors: oestrogen receptor alpha and beta (ERalpha and ERbeta). To
      determine whether these contradictory effects of oestrogen relate to the
      involvement of distinct effects of the two ERs, we investigated expression of
      ERalpha and ERbeta in human secondary lymphoid tissues. We observed that, in
      tonsils, ERbeta is expressed in lymphocytes of germinal centres (GC) and the
      follicular mantle zone as well as in granulocytes, while ERalpha is expressed
      only in activated germinal centres but not in the follicular zone. ERbeta is the
      predominant ER in human leucocytes from peripheral blood, spleen and in
      leucocytes infiltrating cancers in both males and females. In addition, in
      different human lymphoma cell lines including Hodgkin lymphoma, Burkitt lymphoma,
      and multiple myeloma, ERbeta is abundant while ERalpha is not detectable. Our
      results indicate that ERbeta is the predominant type of ER in mature lymphocytes.
      We suggest that ERalpha and ERbeta have distinct roles in secondary lymphoid
      tissues and that further studies with ERbeta-specific agonists will help to
      elucidate the role of ERbeta in these tissues.

PMID- 16294373
TI  - Human breast epithelial stem cells and their regulation.
AB  - This review summarizes the current evidence for the existence of human breast
      stem cells and the pathways involved in their regulation, and discusses how the
      disruption of these pathways may result in the generation of a population of
      cells with the capacity for unlimited self-renewal. Relevant data from mouse
      model systems are also discussed where appropriate. By understanding the
      molecular pathways that regulate self-renewal of normal mammary stem cells, it
      may be possible to target the activation of these pathways in breast tumours.

PMID- 16294374
TI  - New "4-way" vaccine approved...and do multiple vaccines increase immune problems?

PMID- 16294375
TI  - Preventing birth defects with folic acid supplementation.

PMID- 16294376
TI  - Diaper rash--may be due to colored dyes in diapers.

PMID- 16294377
TI  - Allergies. Keep that medical ID tag visible.

PMID- 16294378
TI  - What kids are watching: food ads on TV.

PMID- 16294379
TI  - ICD and pacemaker recalls: do you need a new device?

PMID- 16294380
TI  - Unraveling Alzheimer's disease.

PMID- 16294381
TI  - Diabetes care: zeroing in on neuropathy.

PMID- 16294382
TI  - Stepping out: how to select a walking device.

PMID- 16294384
TI  - Stroke rehabilitation. Helping achieve independence.

PMID- 16294383
TI  - I've been reading a lot lately about the potential health benefits of
      pomegranates. Should I add this fruit to my diet?

PMID- 16294385
TI  - Health tips. Curbing your appetite.

PMID- 16294386
TI  - Annual flu vaccination improves odds for older adults.

PMID- 16294387
TI  - Sleep and aging. Getting the rest you need.

PMID- 16294388
TI  - Bruxism. Breaking the teeth-grinding habit.

PMID- 16294389
TI  - I have an underactive thyroid and take the thyroid drug levothyroxine. I also
      take a calcium supplement to help prevent osteoporosis. I've heard that I should
      take these two at different times of the day. Is this true?

PMID- 16294390
TI  - "Shape-memory" stents fight strokes. Nitinol tubes expand, with body heat, to
      keep carotid arteries open.

PMID- 16294391
TI  - Anti-angina drug shifts heart muscle's fuel use. Compelling the heart to burn
      more blood sugar and less fat appears to boost cardiac efficiency.

PMID- 16294392
TI  - Eat right--and take a walk--to fight diabetes. New guidelines honor patients'
      tastes, but stress value of modest weight loss and exercise.

PMID- 16294393
TI  - "Peace-of-mind" screening tests: worth the out-of-pocket costs? CT scan results
      may motivate some into healthier habits, but alarm others unnecessarily: beware
      of "false positive".

PMID- 16294394
TI  - New gene research finds clues to explain why some die young. But one gene
      variation appears to offer cardiac protection.

PMID- 16294395
TI  - I have been feeling tired lately. My doctor examined me and said that an EKG
      showed evidence of an old heart attack. Wouldn't I know if I had had a heart
      attack?

PMID- 16294396
TI  - Schedule your day for maximum health. Good timing can optimize strategies for
      cardiovascular protection.

PMID- 16294397
TI  - What you really need to know about heart failure (revised).

PMID- 16294399
TI  - Aim for a fast and full recovery. Treatment can help you feel better than you've
      been in years.

PMID- 16294398
TI  - New drugs for prevention, relief. How you might benefit if 3 medications win FDA
      approval.

PMID- 16294400
TI  - Antibiotics vs. heart disease risk. How and why you should protect yourself
      against infection.

PMID- 16294401
TI  - I've just started monitoring my own blood pressure, and notice that my diastolic
      pressure--the lower number--stays pretty much the same but my systolic pressure,
      the higher number, is all over the place. The systolic can easily change by five
      or more, up or down, when I take readings within a minute or so of each other.
      Why? Does this indicate a problem?

PMID- 16294402
TI  - Extreme makeover. Small diet changes = big health payoffs.

PMID- 16294403
TI  - Cold weather increases A1Cs.

PMID- 16294404
TI  - Choosing a meter. Pick one that's right for you.

PMID- 16294405
TI  - Tight control can protect your heart.

PMID- 16294406
TI  - A new "wonder drug"?

PMID- 16294407
TI  - Clinical pharmacists can get you to goal.

PMID- 16294408
TI  - Type 2 early in life could mean kidney problems later.

PMID- 16294409
TI  - Kids, exercise, and night lows.

PMID- 16294410
TI  - Daily foot checks are critical.

PMID- 16294411
TI  - Beyond bean sprouts. Vegetarianism today.  Vegetarian eating can help protect
      your heart and cut your risk of several diseases--and it's more flexible than you
      might think.

PMID- 16294412
TI  - Meat-free and doing fine. When Beverly Mack, RD, decided to become a vegetarian,
      she knew it would take some time. She also knew it was for life.

PMID- 16294413
TI  - The big apple. This versatile fruit is a great fall treat.

PMID- 16294414
TI  - Gastroparesis. An electrical cure? Research profile. Richard McCallum, MD.

PMID- 16294415
TI  - Funding. Activists advise caution on refunding CARE Act.

PMID- 16294416
TI  - California approves HIV/AIDS law to address race disparity.

PMID- 16294417
TI  - Deportation. HIV claim fails to justify immigrant's illegal presence in U.S.

PMID- 16294419
TI  - Liver transplant denial for an HIV-positive woman appealed.

PMID- 16294418
TI  - Medications. Proposed law could lead to discrimination by pharmacists.

PMID- 16294420
TI  - HIV testing order reversed for convicted sex offender.

PMID- 16294421
TI  - Prison. Ohio settles case, promises to improve inmate health care.

PMID- 16294422
TI  - Residential facility excludes man with HIV, disabilities.

PMID- 16294423
TI  - Transmission. New Zealand Court sets worldwide HIV precedent.

PMID- 16294424
TI  - Celecoxib approved for pain relief for AS.

PMID- 16294425
TI  - Anti-virus breakthrough on the horizon. MAVs proteins may play major new role in
      the human immune system.

PMID- 16294426
TI  - NSAIDs sometimes cause fatal stomach bleeding.

PMID- 16294428
TI  - Depression: a symptom of Parkinson's?

PMID- 16294427
TI  - Step lively--live longer. Positive social actions impact health and longevity-
      and guess what?--participants are less likely to die.

PMID- 16294429
TI  - Dramatic benefit seen in new cancer treatment. Herceptin plus chemo shows
      greatest gains compared to any other regimens; may eliminate need for mastectomy.

PMID- 16294430
TI  - "Keyhole" colon surgery minimally invasive.

PMID- 16294431
TI  - Sunlight = prostate cancer protection.

PMID- 16294432
TI  - Common antibiotic may stop OA's progression. Drug slows destruction of cartilage
      but fails to lessen pain.

PMID- 16294433
TI  - Vitamin D daily dose eyed.

PMID- 16294434
TI  - Hypertension: bad at any age. Control your blood pressure to protect against
      heart attack and stroke.

PMID- 16294435
TI  - Natural medication reduces DVT risk.

PMID- 16294436
TI  - Obesity and active life expectancy. A new study finds that obesity affects
      quality of life in older adults more than life expectancy does.

PMID- 16294437
TI  - What is the hearing condition called presbycusis?

PMID- 16294438
TI  - Practice patterns of nonvascular interventional radiology procedures at academic
      centers in the United States?
AB  - RATIONALE AND OBJECTIVES: To determine and analyze the patterns of practice of
      nonvascular interventional procedures in academic centers in the United States.
      MATERIALS AND METHODS: A survey was administered via e-mail to the chief
      residents of 112 academic radiology departments in the United States. Recipients
      of the survey were asked to identify which sections within their respective
      radiology departments performed each of 43 types of nonvascular interventional
      procedures. An additional entry for performance of procedures by non-radiologists
      was provided. A total of 66 (59%) recipients responded. The statistical method
      used was the analysis of contingency tables. RESULTS: Percutaneous abdominal
      biopsies are performed mainly by abdominal and body imaging sections (43/66,
      65%), followed by vascular/interventional sections (21/66, 32%). Percutaneous
      abdominal drainages are performed mostly by abdominal, body imaging, and computed
      tomography sections (40/66, 61%), followed by vascular/interventional sections.
      Fluoroscopically guided procedures were performed most commonly by
      vascular/interventional sections, including percutaneous gastrostomy (40/66,
      61%), percutaneous nephrostomy (42/66, 64%), and biliary interventions such as
      percutaneous transhepatic cholangiography (47/66, 71%). Breast and
      musculoskeletal procedures are performed by their respective sections most
      frequently. Non-radiologists perform a significant portion of certain types of
      procedures: paracenteses, thoracenteses, biliary interventions (particularly
      stone extractions), enterostomies (particularly percutaneous jejunostomies and
      cecostomies), and certain biopsies (kidney and prostate). CONCLUSIONS: Academic
      US radiology sections perform nonvascular interventional radiology procedures in
      a complex and nonuniform manner. The vascular/interventional sections and organ
      system and modality (especially CT) sections perform the bulk of the procedures
      included in the survey. Breast imaging sections predominate in procedures in
      their disciplines. A substantial number and amount of interventional radiology
      procedures are performed by non-radiologists.

PMID- 16294439
TI  - Patent protection for stem cell procedures under the law of the European Union.
AB  - Stem cell research shows an immense diagnostic and therapeutic potential. The
      procedures based on human stem cells seem to allow new medical treatments for
      serious diseases like Parkinson's or Alzheimer's disease, leukaemia or diabetes.
      However, as no company or inventor would take the risk of immense investments
      without an adequate legal protection of the possible benefits arising out of
      their work, intellectual property law plays a pivotal role for the further
      development of stem cell techniques. Although international patent law knows
      protection of inventions using biological substances and living matter for about
      160 years, patents on stem cells, DNA and other parts of the human body raise
      specific objections. Nevertheless, from a strictly legal angle, there are no
      barriers to patents on stem cell procedures. In particular, Art. 6 of the
      "Directive 98/44/EC of the European Parliament and of the Council of the European
      Union of July 6, 1998 on the legal protection of biotechnological inventions" -
      which qualifies inventions as unpatentable where their commercial exploitation
      would be contrary to ordre public or morality - does not hinder patent protection
      for stem cell research.

PMID- 16294441
TI  - Ethics and biomedical research.

PMID- 16294440
TI  - Additional protocol to the Convention on Human Rights and Biomedicine, on
      transplantation of organs and tissues of human origin.

PMID- 16294442
TI  - Phased array magnetic resonance imaging for staging clinically localised
      prostrate cancer.
AB  - Patients suffering from intra-capsular prostate cancer (T1-2, N0, M0) are
      potential candidates for curative treatment by radical prostatectomy or radiation
      therapy. Curative intended therapy is frequently associated with substantial side
      effects, which makes accuracy of preoperative staging important. However, up to
      40% of the patients with clinically localized disease turn out to be under-staged
      and should not have been subjected to curative surgery. The aim of this study was
      to assess the value of preoperative phased array MRI staging in patients who are
      candidates for radical prostatectomy.Ninety-five potential candidates for radical
      prostatectomy suspected of suffering from clinical prostate cancer underwent pre
      diagnostic and pre-operative staging by magnetic resonance imaging (MRI). The
      results were compared with the postoperative pathological findings including
      evidence of extra-capsular extension (ECE) of the tumor. The MRI results were not
      taken into consideration when staging the patients preoperatively or offering
      treatment. Radical prostatectomy was performed within a few weeks after MRI. In
      48 patients the diagnostic biopsy did not detect carcinoma but benign hyperplasia
      of the prostate (BPH), while 9 patients had T3 disease. Thirty-eight patients had
      clinically localized prostate cancer and underwent radical prostatectomy. In 16
      cases (42%) ECE was postoperatively proven by the pathologist, while only 22
      (58%) of the patients suffered from true localized prostate cancer. The
      sensitivity and specificity of MRI detecting ECE were 24% and 86% respectively,
      while the positive and negative predictive value of MRI with regard to ECE were
      only 57% and 61% respectively. Phased array MRI did not in its present form
      provide the necessary accuracy in preoperative staging in clinically localized
      prostate cancer patients.

PMID- 16294443
TI  - Letting die and mercy killing.
AB  - We are all called to make moral decisions, not only about preserving life and
      health, but also about accepting our death and dying. There are situations, when
      it is morally right, and indeed obligatory, to allow a dying person to die in
      peace and dignity. But there is a world of difference between allowing a peaceful
      death, and deliberately setting out to bring death of the person either by acts
      of commission (s.c. 'active euthanasia'), or by acts of omission (s.c. 'passive
      euthanasia'). The word "killing" seems proper for euthanasia, because "to kill"
      does mean " to intentionally cause the death of someone." It can be morally
      acceptable to withhold or withdraw a treatment precisely because it is reasonably
      judged as inefficacious (futile), or excessively burdensome for the patient.
      One's reason for withholding such treatment must not be a judgement about the
      desirability of putting an end to the patient's life, but a judgement about the
      desirability of putting an end to the treatment, which is futile or burdensome.

PMID- 16294444
TI  - Recommendation Rec(2003)10 of the Committee of Ministers to member states on
      xenotransplantation.

PMID- 16294445
TI  - Perspectives of bioethics in the Central and East European context.

PMID- 16294446
TI  - Why is the ethics of euthanasia wrong?
AB  - Human beings are made in the image and likeness of God and are therefore of
      intrinsic worth or value, beyond all prices. Almost all Christian pro-life
      arguments spring from the fountain of personal dignity. Euthanasia would make
      moral sense only if it were possible to say, morally, that this dignity had
      vanished. To commit euthanasia is to act with the specific intention that
      somebody should be nobody. This is the fundamental error of all immorality in
      human relations. To commit euthanasia is to fail to see the intrinsic worth or
      dignity of the person. The judgement that what has worth, intrinsically, somehow
      does not have worth, is both logically and morally wrong. The ethics of
      euthanasia is based on dualistic anthropology and wrong moral presuppositions
      underlying the defence of euthanasia, namely, proportionalism and
      consequentialism. The basic claim of proponents of the ethics of euthanasia is
      that human persons are consciously experiencing subjects whose dignity consists
      of their ability to made choices and to determine their own lives. Bodily life,
      according to them, is a condition for personal life because without bodily life
      one cannot be a consciously experiencing subject. It means that bodily life is
      distinct from personal life. Thus, the body and bodily life are instrumental
      goods, goods for the person, not goods of the person. It thus follows that there
      can be such a thing as a life not worth living--one can judge that bodily life
      itself is useless or burdensome, and when it is, the person, i.e., the
      consciously experiencing subject, is at liberty to free himself of this useless
      burden. Today a key in fighting euthanasia and assisted suicide is better care
      for the sick and dying. The dignity of the sick cannot be erased by illness and
      suffering. Such procedures are not private decisions; they affect the whole
      society. Death with dignity, in the end, is the realisation that human beings are
      also spiritual beings. We have to promote the way of caring for the dying in
      which mercy is extended to the patients without inducing death.

PMID- 16294447
TI  - Euthanasia: the concept and the situation in Turkey.
AB  - This paper gives a brief conceptual and historical overview of euthanasia. These
      are supplemented by considerations of the attitudes to euthanasia and assisted
      suicide in Turkey. At present, euthanasia is neither accepted nor authorised in
      Turkey. This is due both to deontological and legal reasons. It is also not
      regarded positively by the general public.

PMID- 16294448
TI  - Relationships between the Central ("National") Ethics Committee and local ethics
      committees in the Slovak Republic.
AB  - A brief outline about the present relationships between Central ("National")
      Ethics Committee at the Ministry of Health of the Slovak Republic, and the local
      ethics committees in Slovakia is given. The planned improvements concerning the
      function of the system of ethics committees in the Slovak Republic are also
      outlined.

PMID- 16294449
TI  - Ethical code of the pharmaceutical industry in Slovakia. (Excerpts).

PMID- 16294450
TI  - Statement on euthanasia in children.

PMID- 16294451
TI  - Religion and bioethics.
AB  - This paper discusses the role of religious arguments in public bioethical debate.
      It is argued that attempts to rule out religious arguments as valid contributions
      to the pubic debate fails for a number of reasons. There is no non-arbitrary way
      of dividing religious arguments from non-religious arguments, and all arguments
      refer ultimately to a background comprehensive worldview that is never fully
      consistent or coherent and which is furthermore always contested. There are thus
      no good arguments for treating religious arguments differently than any other
      type of argument.

PMID- 16294452
TI  - Statut: centralnej etickej komisie ministerstva zdravotnictva Slovenskej
      Republiky / Statute: Central Ethics Committee Ministry of Health of the Slovak
      Republic.

PMID- 16294453
TI  - Considerations on the scientific and ethical problems related to vegetative
      state.

PMID- 16294454
TI  - One right for all.

PMID- 16294455
TI  - Should voluntary euthanasia be legally permitted?

PMID- 16294456
TI  - Puzzling cases about killing and letting die.
AB  - Discussions of euthanasia often appeal to the distinction between killing people
      and letting them die. Favor asks whether this distinction is morally important-
      in particular, whether killing is worse than merely letting someone die, even
      when the motivations and consequences are the same. She explores our moral
      intuitions via a discussion of various subtly different hypothetical examples.

PMID- 16294457
TI  - Efficacy on climacteric symptoms of a continuous combined regimen of 1 mg 17beta
      estradiol and trimegestone versus two regimens combining 1 or 2 mg 17beta
      estradiol and norethisterone acetate.
AB  - OBJECTIVES: To compare the efficacy of a continuous combined regimen of 1mg
      17beta-estradiol (17beta-E2) and 0.125 mg trimegestone (TMG) with two continuous
      combined 17beta-E2/norethisterone acetate (NETA) combinations in the relief of
      climacteric symptoms in postmenopausal women. STUDY DESIGN: This was a
      randomized, double-blind, multicenter study conducted in 13 countries over a 2
      year period. Healthy postmenopausal women with an intact uterus were treated with
      1 mg 17beta-E2/0.125 mg TMG, 2 mg 17beta-E2/1 mg NETA or 1 mg 17beta-E2/0.5 mg
      NETA for up to 26 cycles, each of 28 days. RESULTS: The 1 mg 17beta-E2/0.125 mg
      TMG combination was effective in significantly reducing the mean daily number and
      severity of hot flushes and in reducing the number of night sweats from cycle 1
      onward. No overall significant differences between this regimen and the
      comparators were detected. Other efficacy variables, including the Kupperman
      index, psychofunctional disorders and quality-of-life sub-scales, experienced a
      similar improvement from baseline with all treatments. CONCLUSION: Continuous
      combined 1 mg 17beta-E2/0.125 mg TMG provides relief of menopausal symptoms that
      is non-inferior to both 17beta-E2/NETA combinations. Furthermore, trimegestone
      appeared to provide a better improvement of depressive mood than 0.5 mg NETA when
      combined with 1 mg 17beta-estradiol.

PMID- 16294458
TI  - A study of the control of climacteric symptoms in postmenopausal women following
      sequential regimens of 1 mg 17beta-estradiol and trimegestone compared with a
      regimen containing 1 mg estradiol valerate and norethisterone over a two-year
      period.
AB  - OBJECTIVE: To compare the efficacy of two sequential 17beta-estradiol (17beta
      E2)/trimegestone (TMG) combinations with the sequential estradiol valerate
      (E2V)/norethisterone (NET) regimen in relieving climacteric symptoms. STUDY
      DESIGN: This was a double-blind, randomized, multicenter study conducted among
      1218 Caucasian (99%) postmenopausal women with an intact uterus in seven European
      countries and Israel, over 13 cycles (each of 28 days). Study duration was
      extended further for 13 cycles, with 531 women receiving treatment for up to 26
      cycles. Treatments consisted of 1 mg 17beta-E2 on days 1-14 and 1 mg 17beta
      E2/0.125 mg TMG or 0.25 mg TMG on days 15-28, and 1 mg E2V on days 1-16 and 1 mg
      E2V/1 mg NET on days 17-28. RESULTS: Rapid and significant reductions in the mean
      daily number and severity of hot flushes and in the mean daily number of
      nocturnal sweats were established in most women with 1 mg 17beta-E2/0.25 mg TMG
      and E2V/NET. These treatments also induced a significant improvement in the
      quality-of-life assessments. CONCLUSION: The 1 mg 17beta-E2/0.25 mg TMG regimen
      provides rapid and effective relief of menopausal symptoms, with a reduction in
      the number of hot flushes "at least as good as" that of the E2V/NET comparator.

PMID- 16294459
TI  - [Proceedings from the 10th Anniversary Workshop in Hepatology, Jurata, Poland, 27
      30 April 2005].

PMID- 16294460
TI  - A comparative 2-year study of the effects of sequential regimens of 1 mg 17beta
      estradiol and trimegestone with a regimen containing estradiol valerate and
      norethisterone on the bleeding profile and endometrial safety in postmenopausal
      women.
AB  - OBJECTIVE: To compare the bleeding profiles and endometrial protection of two
      sequential regimens of 17beta-estradiol (17beta-E2) and trimegestone (TMG) with a
      sequential estradiol valerate (E2V)/norethisterone (NET) regimen. STUDY DESIGN:
      This was a randomized, double-blind, multicenter study conducted in eight
      countries in healthy, postmenopausal women with an intact uterus. A total of 1218
      women were enrolled into the initial 1-year study (13 cycles), and subsequently
      531 of these received treatment for a further year (26 cycles). Treatment
      regimens were 1 mg 17beta-E2 on days 1-14 and 1 mg 17beta-E2/0.125 mg TMG or 1 mg
      17beta-E2/0.25 mg TMG on days 15-28, and 1 mg E2V on days 1-16 and 1 mg E2V/1 mg
      NET on days 17-28. RESULTS: Mean percentage of women reporting onset of
      withdrawal bleeding episodes during the week following discontinuation of
      progestogen was higher in the 1 mg 17beta-E2/0.25 mg TMG group than in the other
      two treatments, showing a more efficient progestogen effect on the endometrium
      and good predictability of bleeding onset with this treatment. The mean numbers
      and average lengths of bleeding episodes were similar in the three treatment
      groups. Overall, the bleeding profile was more favorable with 1 mg 17beta-E2/0.25
      mg TMG than with the lower-dose TMG preparation. Both of the TMG regimens
      demonstrated a good protective effect on endometrial proliferation, with the 0.25
      mg TMG dose showing a lower incidence of proliferative endometrium. CONCLUSION:
      The 1 mg 17beta-E2/0.25 mg TMG regimen showed an adequate protection of the
      endometrium, with an overall favorable bleeding profile.

PMID- 16294461
TI  - Itskov v. New York Fertility Institute, Inc.

PMID- 16294462
TI  - Managing radiation skin injury.

PMID- 16294463
TI  - Evaluation of patients with pain following total hip replacement.

PMID- 16294464
TI  - Using the Roy adaptation model: a program of research in a Military Nursing
      Research Service.

PMID- 16294465
TI  - Functional mobility in older age may depend on gene.

PMID- 16294467
TI  - A brief history of the first dental alumni association in the world
      (organizations associated with the Baltimore College of Dental Surgery).

PMID- 16294466
TI  - A call to sports dietitians: interview with Nanna Meyer. Interview by Louise M
      Burke.

PMID- 16294468
TI  - Our heritage--Thanksgiving.

PMID- 16294469
TI  - President Abramson's report. Annual business meeting--June 2, 1966.

PMID- 16294470
TI  - [More than a futuristic scenario].

PMID- 16294471
TI  - [A profession between technology and magic].

PMID- 16294472
TI  - [Exact supervision in development].

PMID- 16294473
TI  - ["The beautiful new world of nursing"--more than Utopia?].

PMID- 16294474
TI  - [Cooperation in the area of patient care].

PMID- 16294475
TI  - [Raising the quality of life with milieu therapy].

PMID- 16294476
TI  - [Empathic nurses for aged people].

PMID- 16294477
TI  - [First signs for the "new health system" established].

PMID- 16294478
TI  - [The inner cold cannot be dislodged].

PMID- 16294479
TI  - ["I have always had the determination, actively building a frame"].

PMID- 16294480
TI  - [Between the idea and its realization].

PMID- 16294481
TI  - [Influenza vaccine reduces the risk of transmission].

PMID- 16294482
TI  - [Irreplaceable payments].

PMID- 16294483
TI  - [A world where technology and humanity want to come together].

PMID- 16294484
TI  - [Postoperative nurses and acute pain].

PMID- 16294485
TI  - [Defence service].

PMID- 16294486
TI  - [Advanced directives and the end of life].

PMID- 16294487
TI  - [Careholder-value, a barometer for the politics of health].

PMID- 16294488
TI  - [Influenza vaccination reduces the risk of transmission].

PMID- 16294489
TI  - ["Autonomy, truly, is in your head"].

PMID- 16294490
TI  - [In the arms of Morpheus].

PMID- 16294491
TI  - [Informing the patient how to keep clean].

PMID- 16294493
TI  - The AGREE (Appraisal of Guidelines Research and Evaluation) instrument.

PMID- 16294492
TI  - [The Italian Nursing Society gets ready for a new era].

PMID- 16294494
TI  - Domain 1: Scope and purpose.

PMID- 16294496
TI  - Domain 3: Methodological rigor of development.

PMID- 16294495
TI  - Domain 2: Stakeholder involvement.

PMID- 16294497
TI  - Domain 4: Clarity and presentation.

PMID- 16294498
TI  - Domain 5: General applicability.

PMID- 16294499
TI  - Domain 6: Editorial independence.

PMID- 16294500
TI  - Domain 7: Applicability to the German healthcare system.

PMID- 16294501
TI  - Investigation of pharmacokinetic data of hypericin, pseudohypericin, hyperforin
      and the flavonoids quercetin and isorhamnetin revealed from single and multiple
      oral dose studies with a hypericum extract containing tablet in healthy male
      volunteers.
AB  - Hypericins, hyperforin and flavonoids are discussed as the main components
      contributing to the antidepressant action of St. John's wort (Hypericum
      perforatum). Therefore, the objective of the two open phase I clinical trials was
      to obtain pharmacokinetic data of these constituents from a hypericum extract
      containing tablet: hypericin, pseudohypericin, hyperforin, the flavonoid aglycone
      quercetin, and its methylated form isorhamnetin. Each trial included 18 healthy
      male volunteers who received the test preparation, containing 900 mg dry extract
      of St John's wort (STW 3-VI, Laif 900), either as a single oral dose or as a
      multiple once daily dose over a period of 14 days. Concentration/time curves were
      determined for the five constituents, for 48 h after single dosing and for 24 h
      on day 14 at the end of 2 weeks of continuous daily dosing. After single dose
      intake, the key pharmacokinetic parameters were determined as follows: Hypericin:
      Area under the curve (AUC(0-infinity)) = 78.33 h x ng/ml, maximum plasma
      concentration (Cmax) = 3.8 ng/ml, time to reach Cmax (tmax) = 7.9 h, and
      elimination half-life (t1/2) = 18.71 h; pseudohypericin: AUC(0-infinity) = 97.28
      h x ng/ml, Cmax = 10.2 ng/ml, tmax = 2.7 h, t1/2 = 17.19 h; hyperforin: AUC(0
      infinity) = 1550.4 h x ng/ml, Cmax = 122.0 ng/ml, tmax = 4.5 h, t1/2 = 17.47 h.
      Quercetin and isorhamnetin showed two peaks of maximum plasma concentration
      separated by about 3-3.5 h. Quercetin: AUC(0-infinity) = 417.38 h x ng/ml, Cmax
      (1) = 89.5 ng/ml, tmax (1) = 1.0 h, Cma (2) = 79.1 ng/ml, tmax (2) = 4.4 h, t1/2
      = 2.6 h; isorhamnetin: AUC(0-infinity) = 155.72 h x ng/ml, Cmax (1) = 12.5 ng/ml,
      tmax (1) = 1.4 h, Cmax (2) = 14.6 ng/ml, tmax (2) = 4.5 h, t1/2 = 5.61 h. Under
      steady state conditions reached during multiple dose administration similar
      results were obtained. Further pharmacokinetic characteristics calculated from
      the obtained data were the mean residence time (MRT), the lag-time, the peak
      trough fluctuation (PTF), the lowest observed plasma concentration (Cmin), and
      the average plasma concentration (Cav). The data obtained for the five
      consitituents generally corresponded well with values previously published. The
      trial preparation was well tolerated.

PMID- 16294502
TI  - A rapid HPLC method for the determination of losartan in human plasma using a
      monolithic column.
AB  - A rapid and simple high-performance liquid chromatography (HPLC) method using a
      monolithic column has been developed for quantification of losartan (CAS 12450-98
      8) in plasma. The assay enables the measurement of losartan for therapeutic drug
      monitoring. The method involves a simple, one-step extraction procedure. The
      analytical recovery was complete. The separation was carried out in reversed
      phase conditions using a Chromolith Performance (RP-18e, 100 x 4.6 mm) column
      with an isocratic mobile phase consisting of 0.01 mol/L disodium hydrogen
      phosphate buffer-acetonitrile (60:40 v/v) adjusted to pH 3.5. The wavelength was
      set at 254 nm. Thioridazine (CAS 50-52-2) was used as internal standard.
      Losartan, thioridazine and the EXP 3174, the active metabolite of losartan,
      appeared 3.4, 5.0 and 10.5 min post injection, respectively. The calibration
      curve was linear over the concentration range 5-300 ng mL(-1) with a minimum
      detectable limit of 2 ng mL(-1). The coefficients of variation for the inter-day
      and intra-day assay were found to be less than 8 %. The applicability of this
      method for pharmacokinetic studies in humans was demonstrated. The present assay
      is rapid, simple, precise, and accurate and is suitable for pharmacokinetic
      studies.

PMID- 16294503
TI  - Efficacy of troxerutin on streptozotocin-induced rat model in the early stage of
      diabetic retinopathy.
AB  - The vascular changes associated with early diabetic retinopathy, which include
      the formation of microaneurysms and acellular capillaries, vessel dilation,
      vascular endothelial growth factor expression, were investigated experimentally
      in streptozotocin-induced diabetic rats treated with antioxidants: troxerutin
      (trihydroxy-ethylrutoside, CAS 7085-55-4), Vaccinium myrtillus, and calcium
      dobesilate (hydroquinone calcium sulfonate, CAS 20123-80-2). The development and
      progression of retinopathy was followed using fundus photography. After 3 months,
      the rats were sacrificed and half of the eyes were prepared for
      neovascularization analysis, and the other half were used for VEGF (vascular
      endothelial growth factor) analysis. The results from fundus photography and
      ADPase (adenosine diphosphatase) staining were quantified by the percentage area
      of the retinal vasculature using a commercial image analyzer. The VEGF protein in
      the retinal homogenates was assessed using an ELISA (enzyme linked immunosorbent
      assay) kit and VEGF-mRNA by RT-PCR (reverse transcription polymerase chain
      reaction). In the ADPase stain, the retinal vascular percent area increased
      significantly in the diabetic control. Neovascularization and aneurysms were
      observed in the diabetic control and were attenuated by 50 mg/kg troxerutin, but
      the retinal vascular percentage area was not significantly different from the
      diabetic control. The VEGF protein concentration was higher in diabetic rats than
      in the nondiabetic rats (21.5 +/- 2.1 vs 27.7 +/- 5.8 pg/mg, p < 0.05), and this
      increase was attenuated by 10 mg/kg troxerutin (24.5 +/- 3.8 pg/mg, p < 0.05) and
      prevented by 50 mg/kg troxerutin (19.5 +/- 2.2 pg/mg, p < 0.05). However, there
      were no significant differences between the groups. The VEGF-mRNA density showed
      a increasing tendency by 20% in the diabetic rats compared with the non-diabetic
      rats (1.0 +/- 0.1 vs 1.2 +/- 0.1 VEGF/beta-actin), and this increase was
      corrected by 10 mg/kg troxerutin (1.0 +/- 0.1 VEGF/beta-actin), 50 mg/kg
      troxerutin (0.9 +/- 0.1 VEGF/beta-actin) and Vaccinium myrtillus (1.1 +/- 0.1
      VEGF/beta-actin). Oxidative stress might be involved in the upregulation of
      retinal VEGF during early diabetes, and it is likely that troxerutin has
      comparatively effective antioxidant properties. Therefore, troxerutin might be a
      useful treatment for attenuating diabetic retinopathy.

PMID- 16294504
TI  - Pharmacological profile of 9,11-dehydrocortexolone 17alpha-butyrate (CB-03-04), a
      new androgen antagonist with antigonadotropic activity.
AB  - A series of new cortexolone-related derivatives has been synthesized and
      investigated for potential anti-androgenic activity. Among the steroids
      evaluated, 9,11-dehydrocortexolone 17alpha-butyrate (CB-03-04) was the most
      promising one. The compound displayed a strong local antiandrogenic activity in
      hamster's flank organ test, and it was also found to be effective in the rat
      after subcutaneous injection. When compared to other well known androgen
      antagonists, the rank order of topical anti-androgenic activity in that test was:
      cyproterone acetate (CAS 427-51-0) > or = CB-03-04 > finasteride (CAS 98319-26-7)
      > flutamide (CAS 13311-84-7). In addition, the steroid had selective
      antigonadotropic activity, when injected into parabiotic rats, and was about as
      active as progesterone. The activity of CB-03-04 was ascribed mainly to its
      ability to compete with the stimulating effects of testosterone and
      dihydrotestosterone and, concurrently, to inhibit the gonadotropins
      hypersecretion. This bimodal mechanism of action could be predictive for the
      clinical usefulness of the steroid in the treatment of prostate cancer and benign
      prostate hypertrophy.

PMID- 16294505
TI  - Efficient synthesis of isobenzofuran-1(3H)-ones (phthalides) and selected
      biological evaluations.
AB  - The studies presented here deal with the convenient and efficient one-step
      conversion of o-alkylbenzoic acids into their corresponding isobenzofuran-1 (3H)
      ones (phthalides) using NaBrO3/NaHSO3 in a two-phase system. A range of o
      alkylbenzoic acids was used with the object of getting a variety of phthalide
      derivatives as multipurpose biologically active compounds. Seventeen phthalides
      have been synthesized and tested for cytotoxicity, antibacterial and antifungal
      activities. Some of these compounds showed promising cytotoxic effects against
      Artemia salina. Compounds 4j-4p were highly active against Gram-negative and Gram
      positive bacteria among all tested compounds. In the fungicidal assay, the
      compounds showed a broad spectrum of activity against six fungi. All compounds
      were characterized via elemental analysis, UV, IR, mass and-NMR spectroscopy.

PMID- 16294507
TI  - Optimized modified topliss method: a tool for quantitative structure-activity
      relationship studies.
AB  - The structural variation of lead compounds often includes the variation of
      substituents at a particular site. A common difficulty, in quantitative structure
      activity relationship (QSAR) studies, is to select the best substituents to
      obtain, with a minimum number of experiments, a major change in some impor. tant
      properties of the molecule. To improve a proposed modified Topliss method, 187
      different substituted compounds belonging to 70 series were studied. A single
      linear regression was carried out between the experimental activity of each
      series of compounds and the molecular structure parameters pi, sigma, Es and MR,
      along with some combinations of them, in order to select the best substituents
      for constructing the "reduced" correlation. This selection considered the scaled
      smallest residue average of the substituent, the number of times that the
      substituent is inserted in the 70 series and its quadrant in the Craig graph. The
      results obtained in this study with this simple method showed a good predictive
      capacity when compared with the multiple regression analysis, using the Hansch
      method.

PMID- 16294506
TI  - Pharmacokinetic profiling and bioequivalence assessment of two marketed brands of
      nevirapine tablets in healthy Indian volunteers.
AB  - Nevirapine (CAS 129618-40-2), a non-nucleoside reverse transcriptase inhibitor,
      has been effectively used for treatment of HIV-infected patients. A randomized,
      two-way, crossover study was conducted in 24 fasting, healthy, Indian male
      subjects to compare plasma pharmacokinetic profile and single-dose tolerability
      of a new nevirapine tablet formulation (test, T) with that of a reference (R)
      tablet. Each volunteer received T and R formulations separated by at least 19
      days of drug free wash-out period. Plasma concentrations of nevirapine,
      determined up to 288 h post dose by a sensitive and validated HPLC assay, were
      utilized to assess pharmacokinetic parameters such as the maximum observed plasma
      concentration (Cmax), time to Cmax (tmax), and area under plasma concentration
      curve (AUCinfinity). The primary plasma pharmacokinetic parameters of anti
      retroviral substances, Cmax and AUCinfinity, were comparable for either of the
      formulations. Oral absorption of nevirapine was almost complete within 5 h.
      Geometric mean ratios (% reference) of AUCinfinity and Cmax and their 90%
      confidence intervals were 96.9 [93.69-100.24] and 100.8 [94.61-107.4],
      respectively. As the 90% confidence intervals of the geometric mean ratio were
      entirely within 80 to 125% for log-transformed parameters, the two formulations
      were considered bioequivalent in the extent and rate of absorption. Both
      formulations exhibited similar tolerability under fasting conditions.

PMID- 16294508
TI  - [Anti-hormone breast cancer treatment. Convincing trials do exist--we have to
      take up a stand now!].

PMID- 16294509
TI  - [Amlodipine better than atenolol in hypertension. More efficient prevention of
      the mortality and cardiovascular events according to the ASCOT trial].

PMID- 16294510
TI  - [Research ethics guidelines: partly different requirements in various types of
      trials].

PMID- 16294511
TI  - [Life after stroke--a new national study. Renewed follow-up of stroke patients
      shows increased dependency on the support from the next-of-kin].
AB  - The National Board of Health and Welfare together with Riks-Stroke (the Swedish
      National Registry for Quality Assessment of Acute Stroke Care) initiated a follow
      up 2 years after a stroke event in 10,303 individuals, registrated in Riks-Stroke
      during the first 6 months of 2001. The aim was to evaluate the health status of
      the patients and the burden and needs of the spouses. 6,695 patients (65 percent)
      were alive. 4,729 patients (71 percent) answered the questionnaire. 2,367 spouses
      answered a separate questionnaire. This study was compared with an almost
      identical study performed four years earlier. The results showed that more
      patients lived at home and were satisfied with help and support. Rehabilitation
      was still deficient for 30 percent, and more patients were highly dependent on
      support from next-of-kin. Thirty percent could stay alone less than half a day.
      These results will be used for improving rehabilitation for the stroke patients
      and support for their spouses.

PMID- 16294512
TI  - [The AGREE Instrument is a practical method for the assessment of clinical
      guidelines. Quality check of guidelines for asthma/allergy and diabetes in
      Ostergotland].

PMID- 16294513
TI  - [Limit investigation in cancer of unknown primary site].
AB  - Cancer of unknown primary (CUP) is relatively common, approximately 3-5% of all
      cancers. Diagnostic evaluation must include adequate tumor biopsies for pathology
      evaluation (PAD) as well as abdominal and chest CT. Prognosis is generally poor,
      but subgroups occur where long-term survival is possible, and a few patients can
      even be cured. If patients do not belong to any of these subgroups, diagnostic
      evaluation and treatment should be considered in relation to possible benefits.
      CUP diagnosed patients should, if possible, be cared for by experienced hospital
      units with access to a multi-disciplinary network. New radiological methods, such
      as PET and whole-body MRI, may in certain cases provide important information for
      diagnosis.

PMID- 16294514
TI  - [Five seconds...and the gynecologist will cure hydronephrosis/hydroureter].

PMID- 16294515
TI  - [Michelangelo's David has a squint].

PMID- 16294517
TI  - [A new role for physicians in the sick-listing problems?].

PMID- 16294516
TI  - [Establish a team for first-episode psychoses! Time for a nation-wide care
      program model].

PMID- 16294518
TI  - [Final reply on about the Green Party and alternative medicine: Ignorant and
      unethical].

PMID- 16294519
TI  - [Vitamin B12 and folate--a question of balance?].

PMID- 16294520
TI  - [General practitioner and hospital specialist--when do the two meet?].

PMID- 16294521
TI  - [Careless generalization contributes to bad attitude to minorities].

PMID- 16294522
TI  - [We are working on a study about whiplash injuries and eye symptoms].

PMID- 16294523
TI  - ["Time is a heart muscle". Quicker management and reperfusion save more patients
      with ST-segment elevation infarction].

PMID- 16294525
TI  - [Treatment of venous leg ulcers is costly for the health care and the society.
      The value of preventive measures should be further investigated according to a
      study].
AB  - Annual costs for the treatment of venous leg ulcers in Sweden have been estimated
      at between SEK 17,000 and SEK 26,500 per patient in 2002 prices. The calculation
      was based on a model simulation including data from a follow-up of patients in
      clinical practice, an expert panel, and published literature. The variation in
      costs depends on ulcer size and ulcer duration when treatment is initiated. The
      highest costs were estimated for a group of patients with ulcers 10 cm2 or larger
      and ulcer duration of 6 months or longer. About 50 per cent of the total annual
      costs were related to staff costs for dressing changes.

PMID- 16294524
TI  - [Prolonged national economic effects following patient injuries in Swedish health
      care. The single injury is expensive, but the total number of injuries is
      relatively low].

PMID- 16294526
TI  - [Hypothermia after perinatal asphyxia reduces the risk of brain damage. But it's
      too early to recommend the method for routine treatment].
AB  - Two randomised controlled trials evaluating intervention with moderate
      hypothermia after perinatal asphyxia will probably be published this year. The
      first study, evaluating head cooling with a "cool cap" is already published, and
      preliminary data from the other study evaluating body cooling earlier have been
      presented. Both studies indicate that moderate hypothermia, initiated within 6 h
      after birth, for 72 h reduces mortality and survival with severe brain injury.
      Several issues must, however, be solved before postasphyctic cooling can be
      recommended as clinical routine. There are no data on optimal duration, degree of
      cooling, best method, or if methods and degree of cooling should be adapted to
      type of brain injury. Continued research with randomised controlled trials is
      recommended.

PMID- 16294527
TI  - [A case report. Accidental oxygen insufflation via urinary catheter caused
      subcutaneous emphysema].

PMID- 16294528
TI  - [Marburg fever in Angola--the epidemic is over, but the disease is still there].

PMID- 16294529
TI  - [Who owns the discovery, the doctoral candidate or the professor? The
      streptomycin story].

PMID- 16294530
TI  - [Random drug abuse testing--a part of the school health services' preventive
      work!].

PMID- 16294531
TI  - [Finasteride--ris of "unintentional doping"].

PMID- 16294532
TI  - [Wrong use of statistics].

PMID- 16294533
TI  - [Hedbrant is on a slippery slope].

PMID- 16294534
TI  - [Don't judge all carbohydrates alike].

PMID- 16294535
TI  - [Women's "overactive" bladder--a not-evidence-based condition?].

PMID- 16294536
TI  - [The Green Party is wasting money on hocus-pocus].

PMID- 16294537
TI  - [Genetic delusions and ideas in different times].

PMID- 16294538
TI  - [Coronary arterys of France].

PMID- 16294540
TI  - [Secondary prevention of myocardial infarction in the Basse-Normandie region].
AB  - The objectives of this study were to determine post-infarction drug therapy at
      discharge from hospital and at one year in the Basse Normandie region (France)
      and the management of risk factors, to compare them with the practice recommended
      by the French Society of Cardiology and other recent references. Patients whose
      medical expenses were exonerated by the Social Security for primary myocardial
      infarction without a history of angioplasty or of coronary bypass grafting
      between February and September 2002 were reviewed. The data was researched from
      the hospital, the patient, the attending physician and the data bases of the
      Social Security. Four hundred and fifteen patients were included. At discharge
      from hospital the percentages of prescriptions of recommended drugs were as
      follows: betablockers 85%, antithrombotics 99%, ACE inhibitors 75%, lipid
      lowering drugs 90%; the four drug families were associated in 63% of cases. There
      was no significant difference in prescription between hospital discharge and the
      twelfth months except with regards to ACE inhibitors (68%) and the association of
      the four drug groups (54%). The prevalence of smoking, hypertension, diabetes,
      overweight, obesity and dyslipidaemia were respectively 40, 39, 9, 44, 20 and 81%
      at the time of infarction. At one year, the prevalence of smoking had fallen
      significantly to 16%; only 10.3% of patients had uncontrolled hypertension and
      only 29% had not obtained the recommended therapeutic target for LDL-cholesterol.
      The authors conclude that this analysis shows an adequation of drug prescription
      to current recommendations and an improvement in risk factor management which
      should, however, be pursued.

PMID- 16294539
TI  - [French modalities of myocardial revascularisation in 2001].
AB  - French modalities of myocardial revascularization were unknown, whereas
      beneficial effect on outcome was controversial. The study describes current
      practices in 2001 and analyzes those data according to regional coronary heart
      disease incidence and mortality. METHODS: Data are obtained from the French
      hospital national database (PMSI). Mortality is obtained from French mortality
      registry, and myocardial infarction incidence is estimated with French registries
      of MONICA project. RESULTS: Myocardial revascularization utilization fluctuate
      from 25% of patients hospitalized for coronary disease in Limousin to more than
      40% of patients in Provence-Alpes-Cote d'Azur (PACA), Languedoc-Roussillon and
      Ile-de-France. Standardized rate per 100,000 individuals is 109 in Pays de la
      Loire and 309 in Corse. Medical care offers seem to influence the practice. In
      the six regions where the rates are the lower, the density of interventional unit
      and on-pump center are below the national average, and the cardiologist density
      is very low. Consequences on regional clinical outcome of coronary heart disease
      are discussed based on mortality rate and levels of evidenced based medicine in
      myocardial revascularization. CONCLUSION: For the first time, we describe a wide
      variation of regional practices for myocardial revascularization in France. A
      part of those variations can be attributed to regional differences in medical
      care offers. Finally, the impact on clinical outcome appears clearly but seems
      limited. Cardiovascular prevention strategy remains of first line importance and
      emphasizes this main mission of cardiologists.

PMID- 16294541
TI  - [Retrospective study on 100 cases of infective endocarditis, Rabta University
      Hospital, Tunis, from 1980 to 2004].
AB  - This retrospective study describes 100 cases of infective endocarditis (IE),
      collected between 1980 and 2004. Patients were subdivided into 2 groups,
      according to the use of trans-esophageal echocardiography (TOE) in the
      institution where the study was performed: group A (GA=55 patients, between 1980
      and 1991) and group B (GB=45 patients, between 1992 and 2004). The IE cases of 59
      men and 41 women were analyzed. Patients had a mean age of 33 years (range 15-75
      years). An underlying heart disease was involved in all cases, mainly rheumatic
      heart disease (93% of cases). Native valve endocarditis (NVE) was seen in a
      majority of cases (93%), and the localization of IE was aortic in 36 cases,
      mitral in 36 cases, mitro-aortic in 26 cases and mitro-aortic-tricuspid in 2
      cases. Prosthetic valve endocarditis (PVE) occurred in 12 cases. Blood cultures
      were positive in 31 cases, with 14 staphylococcal infections (3 in GA and 11 in
      GB) (p < 0.05), of which 6 were coagulase-negative; 13 were streptococci and 4
      were Gram negative bacilli. All patients had a transthoracic echocardiography
      (TTE), and patients in group B also had a TOE. Seventeen patients had a favorable
      outcome without need of a surgical intervention. Early surgery was necessary in
      71 cases (85.5%), and elective surgery in 12 cases (14.5%). Mortality while
      awaiting surgery was 27%, and has been decreasing for the past decade (41.8% in
      GA and 8.9% in GB) [p < 0.05]. Postoperative mortality after early surgery
      intervention was 13.6% (6 among 44 patients), and it was 8.3% (1 among 12
      patients) after elective surgery intervention. Overall mortality was 34%: 27
      deaths with NVE (30.7% [27/88]), and 7 deaths with PVE (58.3% [7/12]) [NS].
      Predictors of mortality in this observational study were positive blood cultures
      involving staphylococci, the presence of valve mutilations, unstable prostheses,
      and heart failure.

PMID- 16294542
TI  - [Acute myocardial infarction due to spontaneous coronary artery dissection].
AB  - BACKGROUND: Spontaneous coronary dissection is a rare cause of acute myocardial
      infarction (AMI). Its aetiology and treatment have not yet been well defined. In
      this report, we review the clinical presentation, the aetiology, the risk factors
      and the treatment of 6 cases of AMI due to spontaneous coronary dissection.
      METHODOLOGY AND RESULTS: We have reviewed 1100 cases of AMI having undergone
      coronary angiography in our institution during the period December 1999 to
      January 2004. Six cases (0.5%; 5 men, mean age: 38 years) in which spontaneous
      coronary dissection had been retained as final aetiology were further analyzed.
      Four patients had no cardiovascular risk factors but, interestingly, in all 6
      patients we found a clear triggering factor of the acute event: extreme physical
      stress (5), or psychological stress (1). Thrombolysis had been performed in 5
      patients, and the coronary angiography carried out thereafter showed a dissection
      of the left anterior descending coronary (2 cases), of the right coronary artery
      (3 cases) or of the left circumflex artery (1 case). All patients had a preserved
      coronary flow (TIMI 3). On the basis of the angiographical findings, medical
      treatment (4 patients), coronary artery by-pass grafting (1 patient), or
      percutaneous angioplasty with stenting (1 patient) were performed. The only major
      cardiac adverse event observed in the early follow up was a sudden acute
      thrombosis of the coronary stent. CONCLUSION: In young patients without
      cardiovascular risk factors and presenting with AMI subsequent to a physical or
      emotional stress, spontaneous coronary artery dissection should imperatively be
      taken into consideration as a possible diagnosis. Since intravenous thrombolysis
      may worsen the dissection, we recommend primary emergency coronarography as a
      diagnostic and (sometimes) therapeutic treatment option.

PMID- 16294543
TI  - [Intra-individual variability of the platelet anti-aggregation effect of aspirin
      in coronary patients].
AB  - Several studies have reported a biochemical resistance to aspirin in 5 to 10% of
      coronary patients. However, the stability of the platelet anti-aggregation effect
      with aspirin over time remains poorly understood. OBJECTIVE: To study the intra
      individual variability at 6 months of the anti-platelet action of aspirin in
      coronary patients. METHOD: Prospective study including 40 consecutive patients
      with acute coronary syndrome and taking regular aspirin (250 mg a day). The
      biochemical impact of aspirin was determined by measuring the time to occlusion
      (TO) on a collagen/epinephrine cartridge with PFA-100. The determination of the
      TO was performed 2 months (TO1) and then 8 months (TO2) after starting aspirin.
      In our population, a resistance to aspirin was defined as a TO < or =125 sec.
      RESULTS: The median value for TO was generally stable over the two periods, at
      158 sec for TO1 and 179 sec for TO2 (p = 0.29). Among the 9 initially resistant
      patients (22.5%), 4 became sensitive to aspirin without changing the dosage,
      while only one of the 31 initially sensitive patients became biochemically
      resistant. CONCLUSION: the existence of a medium term intra-individual
      variability in the antiplatelet response to aspirin in coronary patients
      underlines the importance of biochemical surveillance in these high vascular risk
      patients.

PMID- 16294544
TI  - [Viral cardiomyopathy].
AB  - In too many cases, the cause of dilated cardiomyopathy (DCM) remains
      undetermined. Coronary or valvular heart diseases, connective tissue disorders,
      toxic causes and signs of infection are systematically investigated. With the
      exceptions of coronary and sometimes valvular heart disease, the treatment of
      cardiac failure remains symptomatic treating the consequences but not the cause
      of DCM, which is therefore diagnosed as "idiopathic". This artericle reports the
      clinical history of 4 patients followed up for apparently "idiopathic" DCM in
      whom the presence of chronic Parvovirus B-19 infection was demonstrated. Based on
      these 4 cases, the hypothesis of an infectious cause of DCM and the role of
      myocardial biopsy, given the progress in molecular biology, are reconsidered.
      Parvovirus B-19 infection has recently been recognised not only as a cause of
      myocarditis but also of chronic viral cardiomyopathy, as in adeno and enteroviral
      infection. The authors conclude that the progress in molecular biology, the
      recognition of a viral aetiology and the efficacy of immuno-modulator therapy
      such as beta-interferon, may lead to a new management strategy of patients with
      DCM in cardiological referral centres.

PMID- 16294545
TI  - [Update on infectious endocarditis].
AB  - Although one of the oldest known cardiac disease, infectious endocarditis (IE)
      remains a subject of constant change from epidemiological, diagnostic and
      therapeutic points of view. In the epidemiological field, the main feature is the
      increasing incidence of IE due to streptococcus bovis. Representing a quarter of
      cases in France, this type of IE is particularly frequent in the elderly and
      underlying colonic disease should be investigated. In the diagnostic field, the
      progress of methods of microbiological identification has been considerable,
      especially in molecular (PCR) and histological diagnosis which are particularly
      useful in IE with negative blood cultures. From the prognostic point of view, the
      role of echocardiography has recently been emphasised not only for diagnosis but
      also for prognosis and for predicting the embolic risk. The longest vegetations
      (>10 or 15 mm) are associated with a greater risk not only of embolism but also
      in terms of prognosis. The recent recommendations of the French Society of
      Cardiology recall the main surgical indications in IE and include a new
      indication of echocardiography.

PMID- 16294546
TI  - [Anaemia, cardiac failure and erythropoietin].
AB  - Anaemia is common in severe cardiac failure due to systolic dysfunction. The
      mechanisms are varied. Anaemia is a negative prognostic factor. Treatment with
      erythropoietin seems to improve the quality of life, functional status, effort
      tolerance and systolic function of these patients. Large scale clinical trials
      are on-going.

PMID- 16294547
TI  - [Significance of the exercise test in hypertensives].
AB  - The presence of hypertension is responsible for an increase in cardiovascular
      morbidity and mortality. The significance of evaluating variations of blood
      pressure on exercise in actual or potential hypertensives warrants further
      consideration. The modes of physiological blood pressure variation on effort and
      the practical methods of performing an exercise test are well documented and have
      been the subject of guidelines. Within this framework must be included dynamic
      exercise tests on ergometric bicycles or with treadmills. From numerous studies
      it is now possible to better define the predictive and prognostic values of the
      various modes of blood pressure changes with exercise. Blood pressure measurement
      on exercise represents an additional investigation in cardiovascular morbidity
      and mortality (coronary or cerebrovascular events). The diagnostic applications
      of this exercise measurement reveal these prognostic data, and exercise blood
      pressure measurement is to be recommended in subjects who experience regular
      significant physical effort.

PMID- 16294548
TI  - [Five years experience with non-pulsatile flow].
AB  - Mechanical circulatory assistances now belong to the therapeutic stock in case of
      advanced heart failure. Their mainspring lays on the substitution of the failing
      left and/or right ventricle function with a pump. The goal being to maintain or
      restore the system main functions. Their main indication is a bridge to
      transplant mechanical circulatory assistance, allowing the patient to await
      transplantation. However, indications for definitive implantation appear in case
      of transplantation counter indication, mechanical circulatory assistances already
      emerging as a possible alternative to transplantation. For over 10 years, we have
      used pulsatile flow assistances, either with pneumatic ventricles or electro
      mechanic implantable left ventricles. We henceforth observe the development of a
      new generation of implantable assistance providing a non-pulsatile flow. These
      are axial pumps. We evaluated the first model, the DeBakey axial pump which
      became the most used axial pump worldwide. We now observe the development of
      other axial pumps as well as the development of new implantable centrifugal
      pumps.

PMID- 16294549
TI  - [Drug-eluting stents: indications, limits and future development].

PMID- 16294550
TI  - [Percutaneous embolisation of a iatrogenic fistula between the internal mammary
      artery and the coronary vein].
AB  - Latrogenic fistula between the aorta and coronary vein is a rare complication of
      coronary bypass surgery due to accidental venous or arterial graft onto a
      coronary vein. The authors report a case of a patient admitted to hospital 2
      months after coronary bypass surgery for cardiac failure due to a iatrogenic
      fistula by implantation of the left internal mammary artery on the great coronary
      vein. This presentation led to the choice of percutaneous embolisation of the
      fistula by the release of 6 coils. Based on a review of the literature, this
      clinical case illustrates the feasibility and value of percutaneous embolisation
      of iatrogenic fistulae.

PMID- 16294551
TI  - [Diagnosis difficulty in occult constrictive pericarditis].
AB  - We report the case of a 42 years woman known to have a cardiac heart failure
      attributed to restrictive cardiomyopathy for want of any other plausible
      diagnosis. Evolution and repeted investigations finally permitted to rectify the
      diagnosis by revealing a constrictive pericarditis, remained occult 9 years
      during. The differentiation of restrictive cardiomyopathy and constrictive
      pericarditis has been a perennial problem in clinical cardiology. Diagnosis of
      constrictive pericarditis is based on associated signs sometimes too poor to go
      straight to thoracotomy. We discuss the mean to approach more precisely this
      uncommon pattern named occult constrictive pericarditis.

PMID- 16294552
TI  - [Adult apico-aortic shunts. A case followed for 6 years].
AB  - An apico-aortic shunt enables a reduction in the aortic transvalvular pressure
      gradient. It is recommended for patients with symptomatic severe stenosis when
      anatomical constraints contra-indicate valvular replacement. The authors report
      the case of a patient who underwent this uncommon procedure, which was indicated
      due to previous coronary bypass surgery using both mammary arteries, plus massive
      calcification of the ascending aorta. Angio-haemodynamic investigation and MRI
      performed three years and five years respectively following the procedure
      confirmed its efficiency. An analysis of the few reported series confirms the
      value of this special procedure.

PMID- 16294553
TI  - [Q fever: a rare cause of endocarditis].
AB  - Coxiella Burnetii endocarditis is very rare. It is the main complication of the
      chronic form of Q fever. Blood cultures are negative and clinical presentation
      very variable and diagnosis is essentially based on indirect immunofluorescence
      serum analysis. The authors report the case of a 19 year old patient with a
      history of rheumatic aortic regurgitation admitted for an episode of left
      ventricular failure in a context of long-term pyrexia without valvular
      vegetations or mutilation. The antiphase I Ig G antibody levels were significant.
      Treatment with doxycycline and fluoroquinolone was initiated. The clinical
      improvement was spectacular. Three months later, the patient underwent aortic
      valve replacement and histological examination of the valve showed subacute
      endocarditis on chronically fibrotic valvular disease. This is an interesting
      case by its rarity and its diagnostic and therapeutic problems.

PMID- 16294554
TI  - [Practical management of medical conflict in hospital practice].
AB  - Practical management of a conflict in hospital practice is based on specific
      rules of administrative law which govern our hospital activity in terms of
      medical responsibility. But beyond this, it calls upon notions of common sense,
      medical and above all civil and diplomatic behaviour, so as not to create a
      critical situation in this already very unpleasant context. The author also
      describes some approach techniques to allow the physician facing this situation
      to extricate himself as well as possible. In addition, all requests for
      explanations, however "aggressive", do not necessarily end in the law courts, and
      that only 15 to 20% of cases prosecuted are eventually found guilty.

PMID- 16294555
TI  - [Screening strategies for the diagnosis of asymptomatic arterial lesions in
      patients with atherothrombosis].
AB  - Atherosclerosis is a ubiquitous inflammatory disease. Patients presenting an
      acute atherothrombotic event (acute coronary syndrom, stroke, aortic aneurysm,
      ...) have an increased risk of events in remote arterial territories affected by
      atherosclerosis. These patients could benefit from systematic screening of
      asymptomatic atherosclerotic lesions to avoid these complications. For each
      atherosclerotic territory (coronary artery, carotid artery, aorta, peripheral
      arteries including renal arteries), we review the methods for screening
      asymptomatic atherothrombotic lesions which could justify specific treatments:
      coronary artery stenosis > or = 50%, carotid artery stenosis > or = 60%, renal
      artery stenosis > or = 50%, and abdominal aortic aneurysm > or = 30 mm. This
      review shows that non invasive methods (ie, echography, tomodensitometry) are
      widely available for diagnosis of asymptomatic lesions in carotid and renal
      arteries, and in the aorta. Despite its invasive caracteristic, coronarory
      angiography remains the gold-standard for the diagnosis of coronary artery
      disease. However, cardiac multi-slices CT-scan appears a promising technique for
      asymptomatic patients.

PMID- 16294556
TI  - [Prevalence of asymptomatic atherothrombotic lesions and risk of vascular events
      in patients with a stroke].
AB  - OBJECTIVE: To estimate the prevalence of asymptomatic atherothrombotic lesions
      and the absolute risk of vascular events in patients with ischemic stroke.
      METHODS: We conducted a systematic review of studies published between 1980 and
      2004 which allowed calculating prevalence of asymptomatic lesions and absolute
      risks of vascular events in stroke patients. Studies included in the review of
      absolute risks had to include at least 100 patients followed for at least 1 year
      and with less than 5% of lost to follow-up. RESULTS: Coronarography was used in
      only one study which does not provide any precise estimation of the prevalence of
      asymptomatic coronary lesions. Depending on the population and the method used
      for the diagnosis of coronary disease, the prevalence of asymptomatic coronary
      artery disease ranged from 25 through 60%. Very few studies have been devoted to
      the prevalence of abdominal aortic disease in stroke patients. The prevalence of
      abdominal aortic aneurysm has been estimated to 1% and that of peripheral
      arterial disease to 10%. Thirty-six cohorts were identified. The absolute risk of
      myocardial infarction was about 2%/year and that of vascular death 2%/year.
      CONCLUSION: Stroke patients carry a high risk of coronary and vascular events.
      Additional studies are required to better identify patients with a high
      prevalence of asymptomatic atherosclerotic lesions and with a high risk of
      vascular events.

PMID- 16294557
TI  - [Prevalence of asymptomatic atherothrombotic lesions and risk of vascular events
      in patients with documented coronary artery disease].
AB  - Coronary arteries are the most frequent location of atherosclerosis. Coronary
      artery disease is the first cause of death related to atherothrombosis. In
      addition, patients with a prior history of acute coronary syndromes exhibit a 10%
      annual risk of recurrence. Although there seems to be a close correlation between
      the extension of CAD and the severity of atherosclerotic lesions in extra
      coronary arterial beds, the prevalence of these extracoronary asymptomatic
      lesions depends on their location. Hence, the prevalence of renal artery disease
      defined as stenosis > or = 50% or of peripheral artery disease defined as an ABI
      < 0.9 is estimated to be 20% up to 30%, whereas the prevalence of both carotid
      artery disease defined as stenosis > or = 70% or aortic aneurysm is estimated to
      be 5%. Conversely, the annual absolute risk of stroke among CAD patients is
      estimated at 1% while it remains unknown for vascular events related to PAD or
      aortic lesions. These data suggest that a systematic screening for asymptomatic
      extracoronary atherosclerotic lesions among CAD patients cannot be justified
      without a better knowledge of the prevalence of these lesions. In addition, the
      identification of the predicting factors for the presence and the development of
      these asymptomatic lesions is warranted. Finally, the potential benefit in terms
      of therapeutic intervention of such screening needs to be evaluated. These
      important issues warrant further clinical studies with appropriate design.

PMID- 16294558
TI  - [Epidemiology of athrotherombotic lower limb arterial disease].
AB  - Chronic occlusive arterial disease of the lower limbs is a common presentation of
      atherothrombotic disease. This systematic review of the literature analyses the
      natural history of this condition and the prevalence of asymptomatic lesions of
      other arterial localisations requiring specific treatment. The Medline database
      was researched and completed by a bibliography of the principal articles
      selected, Internet sites and their publication reviews and also the Cochrane
      database. The incidence of systemic complications has been assessed in many good
      quality epidemiological study. It increases with the severity of lower limb
      arterial disease, but in asymptomatic patients defined by a pathological systolic
      pressure index (< 0.90) the cardiovascular mortality is already 2% per year, the
      incidence of myocardial infarction 3% per year and that of cerebrovascular
      accidents 1 to 2% per year. The prevalence of asymptomatic lesions in other
      arterial sites is less well documented, the evaluations varying according to the
      population studied and criteria of significant lesions: 21 to 69% for coronary
      artery disease, 12 to 59% for carotid artery stenosis, 14 to 40% for renal artery
      stenosis and 6 to 14% for abdominal aortic aneurysms. Despite the uncertainty of
      these estimations, the prevalence of asymptomatic atherothrombotic lesions is
      high in all arterial networks and justifies the setting up of studies to assess
      the clinical benefits of their systematic diagnostic investigations.

PMID- 16294559
TI  - Intimate partner violence.

PMID- 16294560
TI  - Allowing physicians to treat those in need a significant step forward.

PMID- 16294561
TI  - Controlled substance tracking.

PMID- 16294562
TI  - Domestic violence--medicine's response.

PMID- 16294564
TI  - Today's family: declining or adapting?

PMID- 16294563
TI  - The obstetrical dilemma.

PMID- 16294565
TI  - Non-competes: what can practices do?

PMID- 16294566
TI  - Do you understand HIPAA?

PMID- 16294567
TI  - A centennial salute to the American Society of Anesthesiologists.

PMID- 16294569
TI  - Phrenic nerve involvement in Charcot-Marie-Tooth disease.
AB  - Diaphragmatic weakness in Charcot-Marie-Tooth (CMT) disease may be more common
      than generally acknowledged. Recognizing diaphragmatic weakness in a patient with
      CMT is important since recognition of this process may help explain the symptoms
      of breathlessness and orthopnea, as well as the development of hypercarbia.
      Although most patients with CMT have a normal lifespan, the subset of patients
      with diaphragmatic weakness may be at a higher risk of pulmonary morbidity and
      early mortality. Elevation of one or both hemidiaphragms on chest roentgenogram
      should raise the suspicion of diaphragmatic dysfunction and prompt further
      investigation.

PMID- 16294570
TI  - Pertussis: challenges and new opportunities for prevention.

PMID- 16294571
TI  - SAVE marks anniversary with internet safety campaign.

PMID- 16294572
TI  - Client outcomes and the working alliance in assertive community treatment
      programs.
AB  - This study examined the relationship between outcomes and the working alliance in
      clients who were receiving assertive community treatment only or integrated
      assertive community treatment (assertive community treatment plus substance abuse
      treatment). All 98 participants had a severe mental illness and a substance use
      disorder. The Working Alliance Inventory assessed the alliance from the
      perspective of both the client and the case manager at 3 and 15 months into
      treatment. The six outcome measures were stable housing, client rating of
      psychiatric distress, interviewer rating of psychiatric symptoms, self-report of
      days used alcohol or drugs, and interviewer rating of substance use. Only 4 of 24
      correlations were significant, indicating little relationship between the
      strength of the working alliance and client outcome.

PMID- 16294573
TI  - Development and results of a Case Coordination Activity Tracking tool.
AB  - This study describes the development of a tool used to track the who, what, when,
      and how much of case coordination for elderly, community-based clients. The Case
      Coordination Activity Tracking Form measures phase of coordination (assessment,
      plan development, plan implementation, monitoring reassessient, and discharge),
      type of activity (in-person, telephone, documentation, research, travel, case
      conference), with whom contact took place (client, family, client/family
      together, supervisor/colleague, service provider, physician, program access
      committee), and special circumstances (e.g., infection control). Over a 6-month
      span, we used the tool to study case coordination of services for elderly,
      community-based clients. The average amount of coordination time was 5.15 hours
      (n = 234), with 71% of the clients requiring between 2 and 6hours of
      coordination, and 26% of the clients accounting for 49% of the total coordination
      time. Frequency and average amount of coordination declined greatly after the
      first month. Not all clients required coordination each month, and monitoring was
      the most common activity in later months. The tool was found to be reliable and
      easy to use, and of benefit to decision makers, managers, and case coordinators
      in measuring, analyzing, and describing case coordination. This tool could be
      readily used with other client groups.

PMID- 16294574
TI  - Relationship between type of treatment and degree of wound healing among
      institutionalized geriatric patients with stage II pressure ulcers.
AB  - The prevention and treatment of pressure ulcers has always been of paramount
      concern to geriatric health care providers. The purpose of this study was to
      examine the relationship between two types of treatments and the degree of wound
      healing among status post-cerebral vascular accident (CVA) institutionalized
      geriatric patients with stage II pressure ulcers. Wound dressings were evaluated
      according to the National Pressure Advisory Panels Pressure Ulcer Scale for
      Healing (NPUAP, 1997). Fifty long-term care residents were recruited for the
      study in Queens, New York. A convenience sample was randomly assigned to either
      of the treatment protocols: polymeric membrane dressing (polymem) or the
      antibiotic ointment and dry clean dressing (DCD). The findings from the study
      revealed a significant difference in wound healing scores in the polymeric
      membrane-dressing group. These findings are limited due to the small sample size
      and they cannot be generalized to other populations. As this is an initial study,
      further research is recommended

PMID- 16294575
TI  - Special issue of the Journal of Long Term Home Health Care: life issues related
      to cognitive impairment.

PMID- 16294576
TI  - Coping with daily living: housing, finances, transportation, medical care.
AB  - Elderly adults with cognitive impairment may face considerable hurdles in
      navigating through the tasks of daily living. These difficulties may result from
      such factors as diminished organizational skills, reduced physical mobility,
      reduced financial resources, perceptual lapses, and reduced attention, among
      others. The individuals may find it particularly problematic to identify and
      maintain suitable housing to manage finances, to manage their transportation
      and/or utilize public transit. Individuals are also vulnerable to various forms
      of abuse and neglect due to their impairment. We present various cases to
      illustrate such situations and suggest strategies to ameliorate these
      difficulties.

PMID- 16294577
TI  - Cognitively impaired elderly and their adult children.
AB  - An aging parent's development of a cognitive impairment requires significant
      changes in the lives of that individual and his or her family. Adult children may
      be required to assume caregiving responsibilities and may experience feelings of
      loss, as well as conflicting feelings of guilt, apprehension, anger, and
      resentment towards these responsibilities. This article explores the dynamic that
      underlies these sentiments and suggests strategies to maximize parent-child
      communication and facilitate the relationship between cognitively impaired
      elderly adults and their adult children.

PMID- 16294578
TI  - The importance of planning for the future.
AB  - This article explains various mechanisms that are available to plan for the
      future prior to the development of incapacity. These include powers of attorney,
      revocable living trusts, advance medical directives such as powers of attorney
      for health care and living wills, psychiatric advance directives and
      guardianships and conservatorships. Case examples are utilized to illustrate the
      consequences of a failure to plan and what can be accomplished through advance
      planning. The suitability of each such mechanism is dependent on the situation of
      each individual Additionally, the specific details of each mechanism may vary
      across states.

PMID- 16294579
TI  - The participation of cognitively impaired elderly in research.
AB  - It is critical that cognitively impaired adults be permitted to participate in
      research in order to develop a greater understanding of the underlying causes of
      the impairments and strategies to prevent or ameliorate their impact. Significant
      ethical and legal issues may arise in the recruitment and enrollment of these
      persons as study participants, due to difficulties in understanding information,
      uncertainty regarding the existence of sufficient mental capacity to provide
      informed consent to participate, and the potential for coercion to participate as
      a function of limited capacity and dependence on others for care. This article
      explores these issues and suggests mechanisms to maximize the understanding of
      information and facilitate the cognitively impaired elders' expression of choice
      during incapacity.

PMID- 16294580
TI  - Santa Claus and staff retention.

PMID- 16294581
TI  - MedPAC--Quality family time.

PMID- 16294582
TI  - Emergency preparedness for imaging service providers.
AB  - While the images of Hurricane Katrina are still vivid, it is important to draw
      from them the lessons that can be applied to protect patient care services in the
      event of other disasters. It is important that healthcare providers anticipate
      the possibility of these events and plan accordingly. A comprehensive plan
      involves preparation for a disaster, prioritization of the community's immediate
      needs to restore critical patient care services first, and prevention of future
      event impacts. A number of considerations should serve as a starting point for
      conversations regarding a facility's emergency preparedness plan. These involve
      identifying potential natural and man-made disasters, utility interruptions,
      equipment damage, patient transportation, case prioritization, and potential
      outside resources. Some important points to remember when preparing for
      substantial wind and flood damage: Follow original equipment manufacturer (OEM)
      recommendations regarding preemptive equipment power-down/ramp-down,particularly
      for concerns about storm quenches. For magnetic resonance imaging (MRI) scanners
      left running, to p off cryogens, if possible. Cover all non-removable equipment
      with taped-down heavy plastic sheeting to protect against roof failures/leaks.
      Raise all electronic equipment and emergency response supplies as high off the
      floor as safely possible to protect against flooding. Provide adequate food and
      potable water for staff/patients that cannot be evacuated. Prior to the storm,
      contact vendors to secure options imaging equipment, portable generators, and
      cryogen service after the storm passes. If power is lost, restore power to the
      MRI cold-head as quickly as possible.

PMID- 16294583
TI  - Full-field breast tomosynthesis.
AB  - Breast tomosynthesis is a 3-dimensional (3-D) imaging technology that involves
      acquiring images of a stationary compressed breast at multiple angles during a
      short scan. The individual images are then reconstructed into a series of thin
      high-resolution slices that displayed individually or in a dynamic cine mode.
      Tomosynthesis can reduce or eliminate the tissue overlap effect. While holding
      the breast stationary, images are acquired at a nsumber of different x-ray source
      angles. Objects at different heights in the breast project differently for each
      angle. The final step in the tomosynthesis procedure is reconstructing the data
      to generate images that enhance objects from a given height by appropriate
      shifting of the projections relative to one another. There are 3 specific areas
      in tomosynthesis system requirements that warrant a closer review: detector
      efficiency and dose, field of view, and equipment geometry. The breast is
      compressed in a standard way. While holding the breast stationary, the x-ray tube
      is rotated over a limited angular range. A series of low dose exposures are made
      every few degrees, creating a series of digital images. Typically, the tuben is
      rotated about +/-15 degrees, and 11 exposures are made every 3 degrees during a
      total scan of a few seconds. The individual images are projections through the
      breast at different angles and these arewhat are reconstructed into slices. There
      are 2 basic tomosynthesis system designs that diiffer in the motion of the
      detector during acquisition. One method moves the detector in concert with the x
      ray tube so as to maintain the shadow of the breast on the detector. An altemate
      method is to keep the detector stationary relative to the breast platform. The
      tomosynthesis reconstruction process consists of computing high-resolution images
      whose planes are parallel to the breast support plates. Typically, these images
      are reconstructed with slice separation of 1 mm; thus, a 5 cm compressed breast
      tomosynthesis study will have 50 reconstructed slices. The reconstructed
      tomosynthesis slices can be displayed similarly to computed tomography (CT)
      reconstructed slices. Tomosynthesis could resolve many of the tissue overlap
      reading problems that are a major source of the need for recalls and additional
      imaging in 2-D mammography exams.

PMID- 16294584
TI  - Maximizing the imaging center revenue cycle: beginning at the beginning.

PMID- 16294585
TI  - Growing your own: planting seeds for healthy rural hospitals.
AB  - Rural areas continually suffer from shortages of healthcare providers and
      healthcare professionals. Although research exists that addresses unique problems
      and opportunities associated with rural medical careers, little contributes to
      the development of providers from within the community. This article proposes a
      new approach to alleviating the shortage of rural healthcare professionals by
      looking toward the community's youth.

PMID- 16294586
TI  - Determining radiology staffing requirements in the operating room: a radiation
      protection compliance perspective.
AB  - The use of radionuclides and x-ray equipment is highly regulated, and in many
      states, only a licensed technologist or physician may operate the equipment.
      These regulatory requirements, coupled with persistent radiologic technologist
      (RT) vacancy rates, can make adequate staffing a difficult task. While there are
      numerous reports describing nurse workforce requirements, there is a paucity of
      published information on what constitutes appropriate staffing levels for RTs. In
      consideration of future operating room (OR) expansion, the institution determined
      to measure how its current staffing plan was meeting the needs of the OR as well
      as to empirically develop a plan that met all radiation safety and regulatory
      requirements. A 4-week tracking study (N=244 cases) of C-arm and other x-ray
      utilization was performed by 3 RT full-time equivalents (FTE) assigned to operate
      or assist with 10 x-ray devices in 40 ORs. The logs demonstrated that a RT was
      present during 181 cases (181/244 = 74%), while in 63 other cases (63/244 = 26%),
      the RT only delivered the C-arm for physician use. No nurses were observed
      operating the equipment. In some instances, simultaneous requests necessitated
      extra coverage by additional RTs. Regulatory and market forces constrain
      hospitals to make difficult decisions regarding staffing. Objective documentation
      of radiology resource utilization in the OR provided evidence leading to
      improvement opportunities and adjustments to the staffing plan.

PMID- 16294587
TI  - Distance learning: investing in employees' futures.
AB  - The compassion and overall efficiency of those technologists with whom the
      patient interacts impacts the patient's decision to utilize the facility in the
      future. Because employee interaction largely influences patient satisfaction, the
      radiology administrator is challenged to recruit, but more importantly, retain
      quality employees. Benefit options designed to provide employees the latitude to
      achieve personal goals as well as professional obligations can be valuable
      recruitment and retention tools. Ultimately, the purpose of an employee benefit
      is to promote employee satisfaction, leading to employee retention and
      culminating in greater patient satisfaction. Since the "ability to influence
      their career" is reported to be a major area of difference in perceived agreement
      between the technologist and administrator, it is important to consider avenues
      for attaining education and skills to meet employee goals far advance. ment
      within the organization. Distance education, described as a method to provide
      educational offerings without displacing the learner from the workfarce and his
      or her community setting, has been successfully implemented in many allied health
      specialties. Distance learning farmat options include, but not limited to,
      written correspondence courses, audiotapes, video, Internet, and satellite. These
      options provide educational access to those with employment and family
      constraints. The funds that would be spent on recruitment or temporary help can
      be applied toward training or retraining current employees. Typically, one year
      of service is required for each year of schooling funded. In some cases, if the
      training is offered via distance learning, the clinical training portion of the
      educational program can be conducted at the facility sponsoring the student.
      Providing clinical training at a facility reduces the student's learning curve
      associated with transitioning into the open position.

PMID- 16294588
TI  - Time in a bottle.

PMID- 16294589
TI  - Departmental expansion.

PMID- 16294591
TI  - Society attacks med mal challenge on multiple levels.

PMID- 16294590
TI  - The hairpin technology curve.

PMID- 16294592
TI  - Clinical questions #5: Maintenance of normal sinus rhythm after cardioversion: is
      amiodarone better than placebo?

PMID- 16294593
TI  - Public health implications of carrying concealed weapons: have we thought this
      policy through?

PMID- 16294594
TI  - Wisconsin Emergency Assistance Volunteer Registry (WEAVR): how physicians can
      help and why they are needed.
AB  - The Wisconsin Division of Public Health (DPH) and its partners have developed the
      necessary public health infrastructure and core expertise to prepare for, and
      respond to, public health threats and emergencies. The infrastructure includes 12
      public health preparedness consortia that have been established across the state.
      An important part of the response plan is to assure that the responder workforce
      is adequate to meet the need at the local, regional, and statewide levels. The
      responder workforce includes health professional volunteers who, if called on,
      will take on a variety of assigned roles relevant to a defined incident. In order
      to facilitate an organized system for volunteers to indicate their skills and
      availability, DPH has developed a secure and confidential database--the Wisconsin
      Emergency Assistance Volunteer Registry (WEAVR)--to collect and organize contact
      information on health professional volunteers and to make contact with volunteers
      when needed. Physicians, as well as other health professional volunteers, are
      critical to protect the health and safety of the community, especially if the
      need to dispense prophylactic medications or to vaccinate the entire population
      of Wisconsin arises. At the time of an event, volunteers will receive "just-in
      time" training after reporting to their assigned location. In other states,
      physicians have found this emergency training to be of value to their overall
      practice of medicine. Information about how to sign on to WEAVR is provided.

PMID- 16294595
TI  - Menarche and lifestyle.

PMID- 16294596
TI  - The Marshfield Youth Health Study: design, objectives and cohort characteristics.
AB  - PROBLEM: The Marshfield Youth (MY) Health Study was designed to identify parental
      and infant factors associated with childhood and adolescent overweight. METHODS:
      The study examined 867 children (age 5-17 years) from the Marshfield Public
      Schools. Heights and weights were measured by standard methods. Age- and gender
      specific body mass index (BMI) percentiles and z-scores were determined.
      Definitions of overweight from the Centers for Disease Control and Prevention
      were applied. Family characteristics were self-reported by questionnaire and
      included parents' BMI, employment, education, smoking, physical activity; and
      child's daycare attendance, and television/computer use. Maternal and child
      medical records were reviewed. RESULTS: The MY Health cohort included 361
      families. The mean +/- SD age of the children was 12.1 +/- 3.0 yrs; 511 (59%)
      were born in Marshfield, Wis. Of the children studied, 70% had a healthy body
      weight (BMI >5th and <85th percentile); 14.4% were at risk of overweight (BMI >
      or = 85th and <95th percentile) and 13% were overweight (BMI > or = 95th
      percentile). There were no differences in gender or weight status between the
      study cohort and all Marshfield school children (n=2782). CONCLUSIONS: Children
      in the MY Health Study are representative of all school-age children in
      Marshfield. This cohort will be studied to identify factors associated with
      overweight among children.

PMID- 16294597
TI  - Graduated driver licensing in Wisconsin: does it create safer drivers?
AB  - OBJECTIVES: The purpose of this study was to measure the effectiveness of
      Wisconsin's graduated driver licensing law and determine whether a reduction in
      crash rates was due to reduced exposure, safer driving, or both. METHODS: General
      population crash rates for 16 and 17 year olds were computed for years before and
      after graduated drivers licensing. The induced exposure method was used to
      measure exposure and compute the odds ratio of at-fault crash involvement.
      RESULTS: For 16 year olds, general crash rates declined 13.8% while injury crash
      rates declined 15.6%. For 17 year olds, crash rates declined 6.2% for all crashes
      and 5.8% for injury crashes. There was no statistically significant change in the
      odds ratio of at-fault crash involvement for 16- or 17-year-old drivers, relative
      to the reference group. After graduated drivers licensing, 16-year-old drivers
      were more likely to have at least 1 adult present and less likely to carry 2 or
      more teen passengers. There was no statistically significant effect on driving
      habits by time for 16 year olds. CONCLUSIONS: Graduated driver licensing in
      Wisconsin has resulted in a drop in the general population crash rates for 16 and
      17 year olds. This decrease is the result of reduced exposure to the risk of
      collision rather than safer driving by teens.

PMID- 16294598
TI  - Births to teens in Wisconsin: targeting high-risk populations.
AB  - BACKGROUND: Adolescents giving birth represents an important public health issue
      with social, economic, and health-related consequences. OBJECTIVE: Compare birth
      rates and trends in birth rates among adolescents age 15-19 years in Wisconsin
      and the United States by race/ethnicity. METHODS: Teen birth rates from 1998
      2002, and trends in birth rates from 1995-2002 for Wisconsin and the United
      States were compared by race/ethnicity using data from the Wisconsin Interactive
      Statistics on Health and data from the Centers for Disease Control and
      Prevention. RESULTS: The general statewide birth rates and birth rates for
      Wisconsin white teens were lower than national rates, while birth rates for
      black, Hispanic, and American Indian teens were well above national rates from
      1998-2002. Disparities between births to minority adolescents and white
      adolescents were higher in Wisconsin than in the United States. Although teen
      birth rates in general have declined nationally and in Wisconsin, rates among
      Hispanics in Wisconsin have increased during the 1995-2002 period. DISCUSSION:
      Racial disparities in teen birth rates in Wisconsin far exceed national
      disparities. These disparities result from far-ranging, long-term social and
      environmental differences in underlying determinants of health that relate to
      ethnic and cultural beliefs, variation in access to health care that provides
      family planning and reproductive health services, decreased availability of
      school-based clinics, lack of role models, education, and variations in income
      and social status. Wisconsin should focus its teen pregnancy prevention
      activities on the groups at highest risk.

PMID- 16294599
TI  - Tobacco use among adolescents enrolled in Wisconsin Medicaid program.
AB  - PROBLEM: There has been very little study done on tobacco use and cessation among
      the adolescent Medicaid population. Study objectives included determining the
      prevalence of tobacco use among adolescents enrolled in Medicaid, and identifying
      subgroups within this population. METHODS: To determine tobacco use among
      adolescents enrolled in the Wisconsin Medicaid program, we analyzed data from a
      medical chart-audit of health care visits by 11-21 year olds from January 1997 to
      January 1999. RESULTS: Tobacco use status was noted in 55% of adolescent charts.
      Of these, 24% were current smokers, while 38% of adolescents in the general
      Wisconsin population were current smokers. Females had higher rates of tobacco
      use than males (28% versus 11%), and those from rural areas had higher rates than
      those from urban areas (41% versus 17%). Of pregnant adolescents with tobacco use
      status documented, 31.6% were current tobacco users. CONCLUSIONS: Based on the
      data reported, adolescents in the Wisconsin Medicaid program who were pregnant,
      female, or rural residents may benefit from targeted smoking prevention and
      cessation intervention by health care professionals, community coalitions, and
      state programs.

PMID- 16294600
TI  - Asthma and tobacco: double trouble for Wisconsin adolescents.
AB  - BACKGROUND: Environmental tobacco smoke (ETS) exposure has been identified as a
      cause of asthma and a trigger of asthma attacks in children. We examined the
      relation of demographic and tobacco-related risk factors to both lifetime asthma
      diagnosis and the asthma attack rate among Wisconsin adolescents. The impact of
      asthma on adolescent school absenteeism was also examined. METHODS: Data used
      were from the 2004 Wisconsin Youth Tobacco Survey (n=3125), which was
      administered in a sample of Wisconsin public middle and high schools.
      Multivariable logistic regression was used to examine risk factors
      simultaneously. RESULTS: Self-reported lifetime asthma prevalence was 19% among
      Wisconsin adolescents. Thirty-five percent of adolescents with asthma reported
      having an asthma attack in the past 12 months. Living with a smoker was a
      significant predictor of lifetime asthma diagnosis and, among adolescents with
      asthma, daily ETS exposure was associated with a 2-fold increased risk of having
      an asthma attack. Being diagnosed with asthma did not deter adolescents from
      smoking and was a significant predictor of school absenteeism. CONCLUSIONS:
      Asthma is an important health problem for Wisconsin adolescents. Tobacco-related
      risk factors contribute to the burden of the disease. Interventions to reduce
      smoking and ETS exposure targeted to adolescents and their guardians are needed.
      Better asthma control among adolescents could reduce school absenteeism.

PMID- 16294601
TI  - Youth suicide in Wisconsin: mortality, hospitalizations, and risk factors.
AB  - OBJECTIVE: To review Wisconsin data on youth suicide mortality, hospitalizations
      from nonfatal self-inflicted injuries, and self-reported risk behaviors. METHODS:
      Suicide mortality data for youth (defined here as persons 10-24 years of age)
      were obtained from the Centers for Disease Control and Prevention (CDC) for 1995
      2001 and from the Wisconsin Division of Public Health for 2002. Hospitalization
      data for Wisconsin from 1995-2002 were obtained from the Wisconsin Division of
      Public Health. Survey data on self-reported risk behaviors were obtained from the
      CDC for 2001. RESULTS: While the rate of youth suicide declined by 24% in the
      United States during the 9-year period studied, Wisconsin's rate declined only
      slightly (8%). Firearms accounted for 60% of completed youth suicides in
      Wisconsin. Medication overdoses and cutting accounted for 88% of self-inflicted
      injury hospitalizations for Wisconsin youth from 1995 to 2002. Wisconsin high
      school students reported similar rates of risk factor behaviors as youth in New
      Jersey (the state with the lowest suicide rates in the nation), but were more
      likely to use firearms (60% versus 32%). CONCLUSION: Rates of suicide mortality,
      attempts, and self-reported risk behaviors among youth in Wisconsin continue to
      be unacceptably high. Physicians can play an important role in reducing youth
      suicide rates by acting within their clinical practices, as leaders in community
      suicide-prevention activities, and as advocates for policy change.

PMID- 16294602
TI  - Adolescent hospital discharges associated with self-poisonings in Wisconsin, 2000
      2002.
AB  - OBJECTIVE: This study investigates the Wisconsin adolescent self-poisoning
      problem, using state discharge data on medication-related self-inflicted
      injuries, focusing on medications used and risk factors. METHODS: Wisconsin
      inpatient discharge files for 3 years (January 1, 2000-December 31, 2002) were
      evaluated. Medication-related injuries were analyzed for intentionality,
      medications used, discharge status, and risk factors such as mental illness,
      eating disorders, and alcohol abuse or dependence. RESULTS: There were nearly
      3000 medication-related injury hospitalizations--1150 of them self-poisoning
      hospitalizations--among Wisconsin 12-17 year olds during 2000-2002. Females 12-17
      years had twice as many medication-related injuries as males. Sixty percent of
      medication-related injuries occurred in patients with a mental disorder
      diagnosis. Non-narcotic analgesics were most commonly used and had one of the
      highest rates of intentionality (65%). A large proportion of intentional/suicidal
      medication-related injuries were discharged to another facility (35%), compared
      to 14% among all medical injuries. Males with medication-related injuries were
      twice (95% CI: 1.60, 2.75) as likely and females 1.4 (95% CI: 1.2, 1.6) times as
      likely to have intentional/suicidal injuries if they also abused or depended on
      alcohol. CONCLUSIONS: Given that a nonfatal suicide attempt is the strongest
      predictor of eventual suicide, the hundreds of self-poisoning discharges per year
      in Wisconsin 12-17 year olds is a serious public health concern. Both the medical
      community and public health community should heed the warnings of these nonfatal
      suicide attempts and implement educational programs addressing this issue.

PMID- 16294603
TI  - Correlates of age at menarche among sixth grade students in Wisconsin.
AB  - We conducted a cross-sectional, school-based survey of sixth-grade girls living
      in the Reedsburg, Wis area school district to explore factors associated with age
      at menarche. Data collection included parent and student questionnaires for
      demographic, menstrual, physical activity, and nutritional information. School
      nurses conducted physical examinations to provide anthropometric measurements.
      Salivary samples were obtained for laboratory analysis of estradiol, estrone,
      estriol, and progesterone levels. Students (n=59) were an average of 11.9 years
      of age (range: 10-13). Nineteen students (32%) reported menarche, with an average
      of 11.4 years of age (range: 8-12). Cycle length of the menstruating students
      averaged 32.0 days (range: 25-46 days). Students' age at menarche was positively
      correlated with their mothers' age at menarche (r=0.53, P=0.02). Total caloric
      intake, macronutrients, hormone levels, birthweight, and family size were not
      associated with menstrual status. We observed an inverse association between
      increasing weight and earlier age at menarche (P=0.03). Students past menarche
      watched more television (P=0.03) and participated in fewer hours of sporting
      activity (P=0.08) than students who had not yet reached menarche. These
      preliminary data suggest that further investigation of the determinants of
      menarche is both feasible and warranted.

PMID- 16294604
TI  - Jimson weed intoxication in five adolescents.

PMID- 16294605
TI  - Adolescent medicine requires comprehensive array of services.

PMID- 16294606
TI  - New bankruptcy rules leave IRAs mostly safe and sound.

PMID- 16294609
TI  - Can health care improve foreign policy?

PMID- 16294607
TI  - The DOQ-IT initiative: primary care physicians can get help implementing or
      expanding HIT.

PMID- 16294608
TI  - Notification of infectious diseases. 1905.

PMID- 16294611
TI  - Women's narratives of long-term urinary incontinence.
AB  - PURPOSE: The purpose of this study was to use narrative analysis as a method for
      examining the lived experience and meaning of long-term, female urinary
      incontinence (UI). METHOD: Cognitive anthropology and critical medical
      anthropology provided the overall framework for this study. Theoretical
      saturation (Strauss, 1987) was achieved after 17 community-dwelling women with
      long-term (greater than 5 year's duration) UI were interviewed. Informants
      participated in two face-to-face, audiotaped, interviews and a semi-structured,
      topical outline for each interview was used. A field journal was used to
      supplement and validate other data. Informant's narratives were analyzed to
      emphasize the overall plot type of their stories. FINDINGS: In this study, three
      dominant plot types emerged from women's narratives: the UI Quest Narrative, UI
      Restitution and Redemption Narratives, and the UI Victim Narrative. These plot
      types provide a beginning understanding of the lived experience and meaning of
      long-term female UI. CONCLUSIONS: Study findings suggest (a) long-term female UI
      is primarily conceptualized as a condition integrated into a larger life story,
      (b) women with long-term UI relate stories that follow a narrative format, and
      (c) long-term, female UI is heterogeneous. Findings go beyond existing literature
      by suggesting that women's UI narratives serve an important function in
      understanding the lived experience and the meaning of UI.

PMID- 16294610
TI  - Bladder cancer: current optimal intravesical treatment.
AB  - Superficial bladder cancer can be treated surgically, but patients are at high
      risk for recurrence. Tumors are categorized as low, intermediate, and high-risk
      based on grade, stage, and pattern of recurrence. Low-risk tumors are best
      treated with a single instillation of chemotherapy (thiotepa, doxorubicin, or
      mitomycin) (Lamm, 2002). Though effective, the toxicity of bacillus Calmette
      Guerin immunotherapy (BCG) restricts its use to treat higher-grade tumors.
      Intermediate risk tumors can be treated with chemotherapy as well, but will often
      require immunotherapy. High-risk tumors are best treated with intravesical BCG
      using a 3-week maintenance schedule. Side effects of BCG immunotherapy can be
      decreased by logarithmic reductions in dose. Patients who fail BCG may be rescued
      with BCG plus interferon alfa or radical cystectomy.

PMID- 16294612
TI  - Not the surgery for a young person: women's experience with vaginal closure
      surgery for severe prolapse.
AB  - INTRODUCTION: Vaginal prolapse can be debilitating, due to pelvic organ prolapse
      and herniation of the bladder, uterus, intestines and/or support tissues in the
      vaginal opening. However, there is little published information that documents
      women's experiences in the months and years after surgery to correct prolapse.
      OBJECTIVE: This phenomenologic study aimed to increase understanding of the
      specific experiences that patients report after vaginal closure surgery. METHOD:
      Participants were recruited via a mailing to surgical patients from a large
      urogynecologic practice. Semi-structured interviews were tape-recorded and
      transcribed for analysis. RESULTS: Six women participated in the study. After
      analyzing the results, five major themes emerged: awareness and confusion,
      feeling alone in silence, trusting recommendation, acceptance of changed
      sexuality, and still coping. CONCLUSIONS: This small study shows that vaginal
      closure affects an intimate body part and can impact self-image, but the women
      did not regret their changed sexuality. The larger issues for these women were
      ones of communication, information, and isolation, particularly during their
      followup care.

PMID- 16294613
TI  - Self-monitoring and pelvic floor muscle exercises to treat urinary incontinence.
AB  - Urinary incontinence (UI) is a common chronic condition among women. Treatment of
      UI can involve behavioral techniques, pharmacological strategies, or surgical
      intervention. Clinically, treatment strategies should start with the simplest and
      least invasive measures. To overcome the deficiencies in previous research and
      provide definitive information for clinical practice, a randomized clinical trial
      is currently underway. This clinical trial uses a pretest-posttest design to
      first determine the effectiveness of self-monitoring techniques before subjects
      are randomized into one of two treatment groups or an attentional control group
      with a 1-year followup. The study design, sampling plan, and interventions used
      in an ongoing clinical trial to assess the effectiveness of self-monitoring and
      efficacy of biofeedback to treat UI in women are described. Innovative techniques
      to assess adherence to the pelvic muscle exercise protocol are addressed.

PMID- 16294614
TI  - Implementing evidence-based nursing practice.
AB  - A methodology for establishing and supporting evidence-based nursing practice is
      examined. Description of a clinical and administrative scenario serves as an
      example of a systematic appraisal of the relevant literature that had
      implications for clinical practice.

PMID- 16294616
TI  - Management of anticoagulation therapy for invasive procedures.

PMID- 16294617
TI  - Effects of herbal supplements on the kidney.

PMID- 16294618
TI  - Medical assistants: the future nurses?

PMID- 16294620
TI  - Why not ethnography?

PMID- 16294619
TI  - Update on travelers' health.
AB  - As an international traveler, contact your health care provider at least 4 to 6
      weeks before departure to obtain needed vaccinations and prophylactic
      medications. Be aware of the occurrence of any disease outbreaks in the countries
      you are visiting. While traveling, don't forget that one of the most important
      practices in preventing illness from infections is handwashing. Wash your hands
      carefully and frequently with soap and water, and if soap and water are not
      available use an alcohol-based hand rub. Be a responsible traveler by becoming
      informed about health risks and what to do to avoid them before you travel.

PMID- 16294622
TI  - Pediatric home care: continuing issues for the future.

PMID- 16294623
TI  - Pediatric home care: our family's story.

PMID- 16294624
TI  - Gaps in pediatric care: the healthcare providers' challenge.

PMID- 16294625
TI  - A pediatric home health Infection Control Surveillance Program: implementation to
      outcomes.

PMID- 16294626
TI  - A light in the darkness: the StarShine Hospice Program of Cincinnati Children's
      Hospital guides children and families facing the end of life.

PMID- 16294627
TI  - A tribute to Sylvia Drew Ivie and the T.H.E. (To Help Everyone) Clinic.

PMID- 16294628
TI  - The VITAS Innovative Hospice Care approach to pediatric palliative care at home.

PMID- 16294630
TI  - The role of technology in pediatric home care.

PMID- 16294629
TI  - The transition to adulthood by adolescents with chronic respiratory failure: a
      growing challenge.

PMID- 16294631
TI  - Practice makes perfect.

PMID- 16294633
TI  - Too many drugs.

PMID- 16294632
TI  - Q & A: you ask and Sam Geist answers.

PMID- 16294634
TI  - CMS responds to questions regarding Medicare hospice benefit regulations.

PMID- 16294635
TI  - Pediatric home care: issues for the future.

PMID- 16294636
TI  - Good for what ails us. Medical care in coastal Delaware has a long, healthy
      history.

PMID- 16294637
TI  - Suffering: a sixth vital sign?

PMID- 16294638
TI  - Backing up every byte, every night.

PMID- 16294639
TI  - The loss of community rating and its effect on health insurance costs.

PMID- 16294641
TI  - Lori Marciniak. Interview by Amber Brown.

PMID- 16294642
TI  - Keeping the boat afloat: tips on fundraising strategies for your chapter.

PMID- 16294643
TI  - Passion and possibility.

PMID- 16294644
TI  - Advocating for the elderly adult.

PMID- 16294645
TI  - Why choose geriatric nursing? Six nursing scholars tell their stories.

PMID- 16294646
TI  - "Tuning in" to geriatric nursing. Are shortcuts leading to decreased quality of
      care and increased workloads?

PMID- 16294648
TI  - Is that angioplasty really necessary? In the throes of a heart attack, artery
      opening angioplasty is a lifesafer. The same can't be said when it's done to open
      a narrowed heart artery that isn't causing problems.

PMID- 16294647
TI  - Life's quest for spiritual well-being: a holistic and gerontological nurse
      perspective.

PMID- 16294649
TI  - Update: health insurance and utilization of care among rural adolescents.
AB  - CONTEXT: Adolescence is critical for the development of adult health habits.
      Disparities between rural and urban adolescents and between minority and white
      youth can have life-long consequences. PURPOSE: To compare health insurance
      coverage and ambulatory care contacts between rural minority adolescents and
      white and urban adolescents. METHODS: Cross-sectional design using data from the
      1999-2000 National Health Interview Survey, a nationally representative sample of
      US households. Analysis was restricted to white, black, and Hispanic children
      aged 12 through 17 (8,503 observations). Outcome measures included health
      insurance, ambulatory visit within past year, usual source of care (USOC), and
      well visit within past year. Independent variables included race, residence,
      demographics, facilitating/enabling characteristics, and need. RESULTS: Across
      races, rural adolescents were as likely to have insurance (86.8% vs 87.7%) but
      less likely to report a preventive visit (60.1% vs 65.5%) than urban children;
      residence did not affect the likelihood of a visit or a USOC. Minority rural
      adolescents were less likely than whites to be insured, report a visit, or have a
      USOC. Most race-based differences were not significant in multivariate analysis
      holding constant living situation, caretaker education, income, and insurance.
      Low caretaker English fluency, limited almost exclusively to Hispanics, was an
      impediment to all outcomes. CONCLUSIONS: Most barriers to care among rural and
      minority youth are attributable to factors originating outside the health care
      system, such as language, living situation, caretaker education, and income. A
      combination of outreach activities and programs to enhance rural schools and
      economic opportunities will be needed to improve coverage and utilization among
      adolescents.

PMID- 16294650
TI  - Attenuation of racial differences in health service utilization patterns for
      previously uninsured children in the Delta.
AB  - CONTEXT: A school-based health insurance program for children of the working poor
      was conducted in 2 isolated, rural communities in the Lower Mississippi Delta
      region. The larger of the 2 communities had an array of locally available health
      care providers, whereas the smaller community did not. In response to this lack
      of available care, the project designed and delivered outreach programs,
      including transportation to providers. PURPOSE: The purpose of this paper is to
      examine the role of race, age, and gender in the relationships between the
      utilization of care and the impact of outreach programs. METHOD: General
      estimating equation models are used to examine the response of utilization
      variables to race, age, gender, and community. Four years of insurance claims
      data are analyzed. FINDINGS: Race is seen to be an important component of
      utilization. The majority of participants were African American; however,
      children receiving prescription services, emergency room care, routine physician
      visits, and hospital outpatient services were more likely to be white. Outreach
      programs in vision and dental services were found to eliminate racial differences
      and increase utilization. A relatively strong gender effect was found in
      prescription, wellness, vision, and dental services. CONCLUSIONS: Previous
      research has shown differences by race in utilization of care. Our findings show
      that targeted outreach programs can significantly diminish these differences.
      Findings also suggest that barriers to health care for poor rural children are
      closely linked to transportation and availability of providers, not merely to
      cost of care or insurance.

PMID- 16294651
TI  - Psychosocial work characteristics predict cardiovascular disease risk factors and
      health functioning in rural women: the Wisconsin Rural Women's Health Study.
AB  - BACKGROUND: The aim of the present study is to investigate the association
      between psychosocial work characteristics and health functioning and
      cardiovascular disease risk factors among rural women of central Wisconsin and
      compare psychosocial work characteristics between farm and nonfarm women.
      METHODS: Stratified sampling was used to select a random sample (n = 1500) of
      farm and nonfarm women aged 25 to 71 years from the Central Marshfield
      Epidemiologic Study Area. The baseline examination included measurements of blood
      pressure, height, weight, and fasting blood lipids, glucose, and insulin.
      Psychosocial job condition was measured with the Karasek Job Content
      Questionnaires (JCQ). Health functioning was assessed by the Short Form-36 Health
      Survey. RESULTS: The analysis of JCQ showed that nonfarm residents were more
      likely to have jobs with high demand and high decision latitude compared to farm
      residents. Also, the farm residents (40.3%) were more likely to be occupied in
      passive jobs (jobs with low levels of demand and control) than the nonfarm
      residents (26.9%). Among farm residents, psychological job demand was associated
      with HDL level (beta = 0.17), triglycerides (beta = 0.0), their ratio (beta =
      0.005), and blood insulin level (beta = 0.014), and among nonfarm residents,
      psychological job demand was associated with diastolic blood pressure (beta =
      0.17) and total cholesterol level (beta = 0.002). CONCLUSION: Our results showed
      that rural farm residents had a higher prevalence of CVD risk factors and were
      more likely to be occupied in jobs with low levels of demand and control. Job
      stress predicted more CVD risk factors among farm residents compared to nonfarm
      residents. Therefore, interventions reducing job strain among rural farm
      residents are timely and necessary.

PMID- 16294652
TI  - The limited effect of screening for depressive symptoms with the PHQ-9 in rural
      family practices.
AB  - CONTEXT: Previous studies have found that routine screening for depression does
      not improve patient outcome unless it is combined with case management. However,
      these studies were conducted before the widespread use of SSRIs or in settings
      other than traditional primary care. PURPOSE: This study investigated whether
      screening for depressive symptoms improves outcomes for depressed patients seen
      in rural fee-for-service primary care offices. METHODS: Depression screening was
      conducted at 2 private rural clinics in Iowa using the PHQ-9. Patients with
      depressive symptoms were randomized to the control group or the intervention
      group, where providers were given completed PHQ-9 questionnaires at the baseline
      visit. The outcome PHQ-9 scores were assessed by telephone at 4, 10, and 24 weeks
      after the index visit. FINDINGS: A total of 861 patients were screened for
      depressive symptoms; 51 subjects enrolled in the trial. The intervention and
      control groups did not significantly differ with respect to changes in PHQ-9
      scores at any of the 3 follow-up times. They also did not differ with respect to
      the proportion of subjects who were actively managed with medication or by
      referral to a mental health specialist: 46% vs 33% (P = .38) for all subjects and
      50% vs 50% (P = .96) for subjects with major depression at baseline. CONCLUSIONS:
      Screening for depressive symptoms with the PHQ-9 in 2 rural medical clinics did
      not significantly increase physicians' active management of depression or lead to
      improved patient outcomes.

PMID- 16294653
TI  - Depressive symptoms in adolescents living in rural America.
AB  - PURPOSE: The purposes of this pilot study were to examine prevalence of
      depressive symptoms among rural adolescents and identify related social and
      environmental variables. METHODS: A convenience sample of 299 14- to 18-year-old
      agriculture class students at 5 rural high schools in Kentucky and Iowa completed
      a survey that included demographic information, family farm history, experience
      with suicide, perception of school environment, and indicators of farm injuries
      and risky behaviors. Participants also completed the Center for Epidemiologic
      Studies Depression Scale (CES-D) as well as scales to assess the number of major
      life events in the last year, active coping use, and family closeness. FINDINGS:
      The prevalence of a high level of depressive symptoms (CES-D > or = 16) in this
      sample was 34%. Nine percent had seriously considered suicide in the last year.
      Unlike previous reports, boys reported as many depressive symptoms as girls.
      Although the literature reports that engaging in risky behavior is associated
      with depressive symptoms, the only risky behavior linked with depressive symptoms
      in this sample was operating a 4-wheel all-terrain vehicle. Other predictors of
      depressive symptoms included poor family relationships and poor active coping.
      CONCLUSIONS: Interventions to identify and prevent depressive symptoms in rural
      adolescents are needed. Boosting active coping and improving family function may
      also prevent the development of clinical depression in rural adolescents.

PMID- 16294654
TI  - Confronting disparities in diabetes care: the clinical effectiveness of
      redesigning care management for minority patients in rural primary care
      practices.
AB  - CONTEXT: Diabetes mellitus and its complications disproportionately affect
      minority citizens in rural communities, many of whom have limited access to
      comprehensive diabetes management services. PURPOSE: To explore the efficacy of
      combining care management and interdisciplinary group visits for rural African
      American patients with diabetes mellitus. METHODS: In the intervention practice,
      an advanced practice nurse visited the practice weekly for 12 months and
      facilitated diabetes education, patient flow, and management. Patients
      participated in a 4-session group visit education/support program led by a nurse,
      a physician, a pharmacist, and a nutritionist. The control patients in a separate
      practice received usual care. FINDINGS: Median hemoglobin A1c (HbA1c) was not
      significantly different at baseline in the intervention and control groups but
      was significantly different at the end of the 12-month follow-up period (P <
      .05). In the intervention group, median HbA1c at baseline was 8.2 +/- 2.6%, and
      median HbA1c at an average follow-up of 11.3 months was 7.1 +/- 2.3%, (P <
      .0001). In the control group, median HbA1c increased from 8.3 +/- 2.0% to 8.6 +/-
      2.4% (P < .05) over the same time period. In the intervention group, 61% of
      patients had a reduction in HbA1c, and the percentage of patients with a HbA1c of
      less than 7% improved from 32% to 45% (P < 05). CONCLUSIONS: These findings
      suggest that a redesigned care management model that combines nurse-led case
      management with structured group education visits can be successfully
      incorporated into rural primary care practices and can significantly improve
      glycemic control.

PMID- 16294655
TI  - Home-based comprehensive assessment of rural elderly persons: the CARE project.
AB  - CONTEXT: Home-based comprehensive geriatric assessment (CGA) has been effective
      in urban areas but has had little study in rural areas. CGA involves medical
      history taking, a physical exam, and evaluation of functional status, mental
      status, cognitive status, gait and balance, medications, vision, extent of social
      supports, and home safety. We sought to develop and pilot a model of rural home
      based CGA to determine whether successful urban models can be adapted to rural
      areas. METHODS: This study was a developmental demonstration project with
      qualitative and quantitative evaluation components of a home-based CGA model
      using a home health agency and a geriatrician participating from a remote
      location by teleconference. Findings and recommendations were relayed to
      patients, caregivers, and primary physicians. The population studied was elderly
      volunteers (N = 51) aged 75 years and older who did not have a terminal diagnosis
      or immediate plans to enter a long-term care facility. Survey instruments and
      focus groups were used with subjects, family members or caregivers, and
      physicians to generate refinements and outcome measures for the model. FINDINGS:
      Among the 51 patients undergoing CGA, Instrumental Activities of Daily Living
      dependency and balance and gait problems were highly prevalent. Means of 1.1
      major problems and 4.9 nonmajor problems were identified per patient.
      Recommendations were implemented for 32% of major problems and for 35% of
      nonmajor problems. Primary physicians found recommendations for vaccination and
      home safety change helpful but were skeptical of physical examination findings by
      the nurse. Practitioners noted that this study resulted in several positive
      outcomes: (1) some subjects initiated regular clinic visits; (2) several visually
      impaired elders began services for the blind; (3) identification of gait and
      balance problems resulted in physical therapy treatment; and (4) identification
      of caregiver stress was addressed by social-work intervention. Potential further
      refinements of the model for rural home-based CGA were identified. CONCLUSIONS:
      Home-based CGA identifies important problems of rural older adults. However,
      modifications are still needed to create a truly effective process.

PMID- 16294656
TI  - Challenges and strategies related to hearing loss among dairy farmers.
AB  - CONTEXT: Farming is often imagined to be a serene and idyllic business based on
      historical images of a man, a horse, and a plow. However, machinery and equipment
      on farms, such as older tractors, grain dryers, and vacuum pumps, can have noise
      levels, which may be dangerous to hearing with prolonged, unprotected exposure.
      PURPOSE: This qualitative study in Ontario, Canada, explored the challenges and
      coping strategies experienced by dairy farmers with self-reported hearing loss
      and communication difficulties. Through in-depth interviews, 13 farmers who
      experience significant hearing loss were questioned about the challenges they
      face as a result of hearing loss and the strategies they use to overcome or
      compensate for problems. FINDINGS: The 2 major challenges encountered by dairy
      farmers with a hearing loss were: (1) obtaining information from individuals,
      within groups, and through electronic media; and (2) working with animals,
      machinery, and noise. To cope with these challenges, participants used strategies
      identified as problem and emotion focused. CONCLUSIONS: Four themes arose from
      analysis of the challenges encountered and strategies used: 1. Hearing loss is
      experienced as a "familiar," but "private," problem for dairy farmers. 2.
      Communication difficulties can negatively affect the quality of relationships on
      the farm. 3. Safety and risk management are issues when farming with a hearing
      loss. 4. The management or control of excessive noise is a complex problem,
      because there are no completely reliable yet practical solutions.

PMID- 16294657
TI  - Diabetes beliefs among low-income, white residents of a rural North Carolina
      community.
AB  - CONTEXT: Every social group shares beliefs about health and illness. Knowledge
      and understanding of these health beliefs are essential for education programs to
      address health promotion and illness prevention. PURPOSE: This analysis describes
      the diabetes Explanatory Models of Illness (EMs) of low-income, rural, white
      Southerners who have not been diagnosed with diabetes. METHOD: In-depth
      interviews were conducted with low-income white women (n = 19) and men (n = 20)
      aged 18 to 54 years who resided in a rural Southern town. The tape-recorded
      interviews were completed by trained interviewers and were transcribed verbatim.
      Computer-assisted text analysis was used, and all transcripts were coded by 2
      investigators. FINDINGS: Although all the participants had heard of diabetes,
      their EMs were vague and undeveloped. Women were more knowledgeable than men
      were. Family and heredity were widely believed to be causes, with heredity
      including genetic and learned behavior components. Participants disagreed about
      the role of diet and weight in causing diabetes; exercise was not perceived as
      related to causation. Participants had knowledge of those symptoms,
      complications, and treatments that could be observed. CONCLUSIONS: These rural,
      white Southerners did not share well-developed EMs for diabetes, with most having
      a vague and incomplete understanding of this disease. The diabetes beliefs of
      these rural Southerners differ significantly from current medical knowledge. To
      be effective, culturally appropriate primary prevention programs must recognize
      these lay beliefs.

PMID- 16294658
TI  - Rural medical school applicants: do their academic credentials and admission
      decisions differ from those of nonrural applicants?
AB  - CONTEXT AND PURPOSE: Medical schools located in states with sizable rural areas
      are concerned about preparing physicians for practice in these areas; this is of
      particular concern for medical schools that are part of a state-owned university
      with a responsibility to educate physicians for rural areas. Because individuals
      from rural areas are most likely to return to practice medicine in rural areas at
      the conclusion of their training, it is important to recruit these individuals to
      medical schools to educate them for rural practice. METHODS: This study examines
      7 years of admission data for students who applied and were accepted to the
      University of Missouri-Columbia School of Medicine, which has as a specific
      mandate to prepare physicians for rural practice. FINDINGS: The study indicates
      that rural applicants are more likely to be admitted to the medical school, and
      based on admissions criteria they are at least as academically qualified as
      nonrural applicants. CONCLUSIONS: The study demonstrates that a medical school
      can maintain competitive admission criteria while at the same time accepting
      those students more likely to enter rural practice. This is valuable information
      that medical schools with a similar mission to prepare physicians for rural
      practice might consider in their admissions decision-making process.

PMID- 16294659
TI  - The Montana model: integrated primary care and behavioral health in a family
      practice residency program.
AB  - To address the local health care needs of both patients and primary care
      providers in Montana, an integrated primary care and behavioral health family
      practice clinic was developed. In this paper we describe our experience with
      integrating mental health and substance abuse services into a primary care
      setting (a community health center) while simultaneously teaching family practice
      physicians to take the lead in providing these services. The Deering Community
      Health Center in Billings, Montana, is a Federally Qualified Health Center
      serving a largely low-income patient population. The medical care at the clinic
      is provided primarily by the faculty and residents of the Montana Family Medicine
      Residency. The teaching model was founded on the belief that improved care will
      result when physicians have increased comfort with, and are able to enjoy the
      challenges of, patients with mental illnesses. The enhanced longitudinal
      curriculum incorporates mental health across the 3 years of the family practice
      residency. Unique characteristics of this model include staffing and the
      concurrent delivery of a high volume mental health service while teaching family
      practice resident physicians and the faculty to integrate this competency into
      their primary care practices.

PMID- 16294660
TI  - Physician assistant and nurse practitioner prescribing: 1997-2002.
AB  - CONTEXT: Physician assistants (PAs) and nurse practitioners (NPs) have licensure
      to practice in all states and they have prescriptive authority in 47 and 40
      states, respectively. However, there have been no published studies from a
      national standpoint comparing urban and rural settings. PURPOSE: The objective of
      this study was to describe the characteristics of providers, patients, and the
      type of prescriptions written by PAs and NPs and to compare these activities to
      those of physicians in metropolitan and nonmetropolitan settings. METHODS: The
      National Ambulatory Medical Care Survey was used to analyze a representative
      sample of 149,202 visits to primary care physician offices over a 6-year period
      (1997-2002) in which a prescription was written by a PA, NP or physician.
      RESULTS: A PA or NP was the provider of record for 3% of the primary care visits.
      The 3 providers wrote prescriptions for 60% to 70% of all visits, and the mean
      number of prescriptions was 1.3 to 1.5 per visit (range 0-5), depending on the
      provider. PAs were more likely to prescribe a controlled substance than were
      physicians or NPs (19.5%, 12.4%, 10.9% respectively). Only in rural areas did
      differences emerge. In rural areas, NPs wrote significantly more prescriptions
      than physicians and PAs, and PAs wrote significantly fewer prescriptions than the
      other providers. CONCLUSIONS: Overall, PAs and NPs are prescribing in a manner
      similar to physicians in the type of medications used in their patient
      management. In nonmetropolitan areas, prescribing differences among the 3 types
      of providers bear further exploration.

PMID- 16294661
TI  - Comparative description of migrant farmworkers versus other students attending
      rural south Texas schools: substance use, work, and injuries.
AB  - CONTEXT: Little is known about substance use, work characteristics, and injuries
      of youth from migrant farmworker families. Some evidence suggests that migrant
      youth may be at greater risk for substance use and work-related injuries than
      nonmigrant youth. PURPOSE: The aim of this study is to compare substance use,
      employment, and injury data from migrant and nonmigrant youth residing in rural
      South Texas. METHODS: Anonymous cross-sectional survey data were collected from
      7,302 middle and 3,565 high school students during a regular class.
      Classification as a migrant student occurred if the student responded positively
      to: "Does your family move around the state or nation to pick fruits or
      vegetables for work?" RESULTS: About 5% of South Texas middle and high school
      students reported belonging to a migrant family. Compared to nonmigrant students,
      migrant youth were more likely to report frequent substance use. Youth belonging
      to migrant families were less likely to work for pay on weekends but more likely
      to work for pay on weekday mornings before school. These youth were also more
      likely to have ever been injured while working than nonmigrant students.
      CONCLUSIONS: These results demonstrate a need for additional interventions in
      this most vulnerable rural population. Specifically, targeted educational
      programs to enhance the occupational safety and health of migrant youth, further
      research into effective substance abuse treatment and prevention programs in
      rural areas, and enhancement of child labor laws are recommended.

PMID- 16294662
TI  - Modeling the emergency ambulance pass-by of small rural hospitals in Victoria,
      Australia.
AB  - CONTEXT: Many small rural hospitals struggle to attract sufficient numbers of
      suitable patients. Inadequate patient throughput threatens the viability of these
      hospitals and, consequently, the financial, physical, and social well-being of
      the whole community. Anecdotal evidence suggests that many emergency ambulance
      patients are routinely taken past their local small rural hospital to the area's
      major receiving hospital. PURPOSE: To quantify the ambulance pass-by of local
      small rural hospitals and identify the factors that influence its occurrence.
      METHODS: Data were collected from the ambulance and hospital records of 3 small
      rural centers in central Victoria, Australia. RESULTS: Ambulances transport a
      significant number of patients past their local small rural hospitals to the
      area's major receiving hospital. This takes less time for paramedics than
      bringing a patient to the local hospital first if the patient is then redirected
      by that hospital to the larger hospital. There is an inverse relationship between
      the rate of cases in which the local hospital redirects ambulances to the
      regional hospital and the rate of ambulance crew decisions to use the local
      hospital. CONCLUSIONS: If some patients are being transported directly to the
      major receiving hospital because paramedics are considering their own time
      commitments when making patient transport decisions, this could have revenue
      implications for rural hospitals. Attracting appropriate local ambulance patients
      to the smaller hospitals may provide an income source that is currently lost to
      the crowded major receiving hospital's emergency department.

PMID- 16294663
TI  - Accessibility assessment of the Health Care Improvement Program in rural Taiwan.
AB  - CONTEXT: An experimental Health Care Improvement Program (HCIP) was initiated by
      the Bureau of National Health Insurance in 1997 to improve the accessibility of
      health care in several rural, mountainous districts. PURPOSE: This longitudinal
      study evaluated service availability, utilization patterns, and effectiveness of
      services under the HCIP in the A-Li Mountain District. METHODS: Outpatient claims
      made by residents in the A-Li Mountain District were extracted from the database
      of the National Health Insurance program. Changes in utilization pattern and
      volume were analyzed. Satisfaction levels were assessed by 2-stage face-to-face
      interviews with local residents. FINDINGS: After the HCIP, the average population
      served by each doctor decreased 75%, and total outpatient visits increased 15.4%.
      The total number of in-district outpatient visits increased 83.6%. The proportion
      of in-district outpatient visits to all visits increased from 22.1% to 35.1%. The
      total in-district outpatient visit fee claimed increased 100.2%, and the total
      out-of-district outpatient visit fee claimed increased only 7.2%. About 60.4% of
      the residents were not satisfied with overall health care services before the
      HCIP. The proportion decreased to 32.4% after the HCIP. CONCLUSIONS: The HCIP
      improved accessibility, enriched local medical care resources, changed the
      utilization pattern of some residents, and increased residents' satisfaction
      level. A well-managed program with stabilized financial resources is more likely
      to succeed if it also respects cultural differences and responds to community
      needs.

PMID- 16294665
TI  - Healing touch: hands-on help for the heart? Touch therapies are reaching growing
      numbers of patients.

PMID- 16294664
TI  - The relationship of individual, family, and community characteristics with
      physical health: an adult study in 27 rural Minnesota counties.
AB  - CONTEXT AND PURPOSE: This study; investigates associations between the proportion
      of farm families in rural counties and the health of rural individuals,
      independent of county poverty rate and individual and family socioeconomic
      factors. This study also examines relationships of these socioeconomic factors
      and prevalence of specific diseases. METHODS: Multilevel analysis of 10,485
      responses to a mailed health survey in 27 nonmetropolitan Minnesota counties.
      FINDINGS: Individual- and family-level variables such as age, gender, lower
      income, and unemployment were significantly associated with adverse physical
      health. The percentage of farm families in counties was significantly associated
      with adverse physical health of adults, independent of individual and family
      characteristics, county poverty rate, ethnic composition, and population density.

PMID- 16294666
TI  - North Mississippi Medical Center: a focus on quality, safety, and financial
      critical success factors.
AB  - BACKGROUND: North Mississippi Medical Center (NMMC), the largest rural hospital
      in the United States, offers a continuum of health care services stretching from
      high-tech trauma and/or cardiac care through to compassionate home, long-term, or
      hospice care. OVERALL APPROACH TO QUALITY AND SAFETY: NMMC uses a care-based cost
      management (CBCM) approach to performance improvement, which is used to look
      beyond traditional cost drivers (people, equipment, supplies) to the care issues
      that have a much greater impact on the actual cost of care-practice variation,
      complications, and social issues. APPROACH TO ADDRESSING THE SIX IOM QUALITY
      AIMS: The CBCM approach addresses NMMC's quality, safety and financial critical
      success factors and is applied to address the six Institute of Medicine quality
      aims. For example, by conceptualizing "patient safety" to include appropriate
      care for every patient, CBCM leads directly to IOM aims and evidence-based
      practice. Physician champions and nurse outcomes managers liaison with providers
      to achieve decreased complications, analyze practice variation from best
      practice, and address social issues that impair care improvement. CHALLENGES AND
      LESSONS LEARNED: One of NMMC's greatest challenges is to continuously improve the
      health of the people in its region. Since 1995, it has partnered in periodic
      community health assessments to examine its wellness initiatives and plan
      programs.

PMID- 16294668
TI  - El Camino Hospital: using health information technology to promote patient
      safety.
AB  - BACKGROUND: El Camino Hospital is a leader in the use of health information
      technology to promote patient safety, including bar coding, computerized order
      entry, electronic medical records, and wireless communications. OVERALL APPROACH
      TO QUALITY AND SAFETY: Each year, El Camino Hospital's board of directors sets
      performance expectations for the chief executive officer, which are tied to
      achievement of local, regional, and national safety and quality standards,
      including the six Institute of Medicine quality dimensions. He then determines a
      set of explicit quality goals and measurable actions, which serve as guidelines
      for the overall hospital. The goals and progress reports are widely shared with
      employees, medical staff, patients and families, and the public. ADDRESSING THE
      SIX IOM QUALITY AIMS: For safety, for example, the medication error reduction
      team tracks and reviews medication error rates. The hospital has virtually
      eliminated transcription errors through its 100% use of computerized physician
      order entry. Clinical pathways and standard order sets have reduced practice
      variation, providing a safer environment. CHALLENGES: Many projects focused on
      timeliness, such as emergency department wait time, lab turnaround time, and
      pneumonia time to initial antibiotic. Results have been mixed, with projects most
      successful when a link was established with patient outcomes, such as in reducing
      time to percutaneous transluminal coronary angioplasty for patients with acute
      myocardial infarction.

PMID- 16294667
TI  - NewYork-Presbyterian Hospital: translating innovation into practice.
AB  - BACKGROUND: NewYork-Presbyterian (NYP) Hospital, a 2,242-bed not-for-profit
      academic medical center, was formed by a merger of The New York Hospital and The
      Presbyterian Hospital in the City of New York. It is also the flagship for the
      NewYork-Presbyterian Healthcare System, with 37 acute care facilities and 18
      others. OVERALL APPROACH TO QUALITY AND SAFETY: The hospital embeds safety in the
      culture through strategic initiatives and enhances service and efficiency using
      Six Sigma and other techniques to drive adoption of improvements. Goals are
      selected in alignment with the annual strategic initiatives, which are chosen on
      the basis of satisfaction surveys, patient and family complaints, community
      advisory groups, and performance measures, among other sources. USE OF
      INFORMATION TO SET AND EVALUATE QUALITY GOALS AND PRIORITIZE INITIATIVES: A new
      business intelligence system enables online, dynamic analysis of performance
      results, replacing static paper reports. Advanced features in the clinical
      information systems include computerized physician order entry; interactive
      clinical alerts for decision support; a real-time infection control tracking
      system; and a clinical data warehouse supporting data mining and analysis for
      quality improvement, decision making, and education. APPROACH TO ADDRESSING THE
      SIX IOM QUALITY AIMS: To achieve clinical, service, and operational excellence,
      NYP focuses on all Institute of Medicine quality aims.

PMID- 16294669
TI  - Lehigh Valley Hospital: engaging patients and families.
AB  - BACKGROUND: Lehigh Valley Hospital (LVH), a 623-bed tertiary care referral
      center, is one of two hospitals of the Lehigh Valley Hospital and Health Network.
      PATIENT AND FAMILY INVOLVEMENT: Improving patient safety requires active
      engagement. Many units have collaborative rounds, which family members may join.
      Family meetings often include multimedia sources to review patient conditions,
      results, and plans of care. LVH's advanced intensive care unit program allows
      virtual meetings with an off-site intensivist. USE OF INFORMATION TO SET AND
      EVALUATE QUALITY GOALS AND PRIORITIZE INITIATIVES: The Institute of Medicine
      (IOM) aims of care are addressed in terms of Donabedian's clinical outcomes
      (safety, effectiveness, and timeliness), financial outcomes (efficiency), and
      service outcomes (patient-centeredness and equity). APPROACH TO ADDRESSING THE
      SIX IOM AIMS: Two strategies to address the IOM's six aims have been employed-
      patient engagement and an emphasis on technology. More than $30 million has been
      invested, thereby creating a digital hospital, which, in combination with
      evidence-based practice, uses advanced computerized and wireless systems to
      improve patient care and safety. CHALLENGES AND LESSONS LEARNED: New problems
      evident once process improvements are made are quickly addressed. Technology
      cannot fix bad processes; rather, process improvements should come first, with
      technology then added to enhance those improvements.

PMID- 16294670
TI  - Publicly reporting comprehensive quality and cost data: a health care system's
      transparency initiative.
AB  - BACKGROUND: Transparency in health care, including the public reporting of health
      care results, is an expanding and unstoppable phenomenon. Health care systems
      have an opportunity to: (1) be proactive and accountable for the care they
      provide, (2) help patients learn more about their condition as a supplement to
      understanding the performance measures, and (3) use public reporting to foster
      process of care and outcome improvement initiatives. An overview is provided of
      the first 22 months of a transparency initiative at Dartmouth-Hitchcock Medical
      Center (DHMC). LAUNCHING THE TRANSPARENCY INITIATIVE: An interdisciplinary
      operations group works with the various clinical programs--both providers and
      patients--to identify what quality and cost measures are most desired by patients
      and what measures are the focus of the clinical program's internal measurement
      and reporting processes. The measures are presented on the DHMC Web site, with
      access to additional resources, such as clinical decision aids. DISCUSSION: A
      variety of factors are important to the transparency initiative--senior leaders'
      perceptions, risk management issues, resources required for the design and
      maintenance of the initiative, and developing both methodological protocols and
      technical systems.

PMID- 16294671
TI  - Integrating the intensive care unit safety reporting system with existing
      incident reporting systems.
AB  - BACKGROUND: Voluntary incident reporting systems that identify risks can be
      integrated into existing hospital reporting systems and can improve patient
      safety. FINDINGS: A voluntary and anonymous Web-based intensive care unit safety
      reporting system (ICUSRS) was implemented in a cohort of intensive care units
      (ICUs). The reporting system was integrated into hospitals' reporting systems
      after the adverse event reporting structures were investigated. Reporting systems
      were classified as mandatory or voluntary and internal or external; the extent of
      formal training was identified and the trajectory of completed adverse events in
      the exisiting systems were tracked. Information from reported incidents was sent
      back monthly to the hospital ICUs through case discussions and a quarterly
      newsletter. RESULTS: All seven hospitals had internal reporting systems and two
      also used external reporting systems. In general, the majority of incident
      reports were completed by registered nurses and were reported to the nursing
      chain of command. Many of the sites had little knowledge or understanding of
      their existing reporting systems. CONCLUSION: Voluntary external reporting
      systems such as the ICUSRS hold promise for improving patient safety.

PMID- 16294673
TI  - Is blood like your waistline--the thinner, the better? An interesting theory
      proposes that watering down your blood can prevent heart disease. Don't overdo
      it.

PMID- 16294672
TI  - Intimidation: practitioners speak up about this unresolved problem.
AB  - A survey suggests that health care providers' intimidating behaviors are not
      isolated events, but many actions can be undertaken to reduce their frequency.

PMID- 16294674
TI  - Nonprofit hospitals face structural as well as financial challenges: lessons from
      Massachusetts.
AB  - Like most nonprofit hospitals, those of Massachusetts are facing serious
      financial challenges. Although the immediate issue is the shortfall between
      revenues and expenses, the author finds that the real problems are systemic,
      evidenced by at least three structural impediments: uncompensated care, overuse
      of teaching hospitals, and an increasingly unattractive environment for the
      practice of medicine. Other states whose nonprofit hospitals face persistent
      financial difficulties may find it useful to consider whether (similar or
      different) structural impediments are also undermining the operating performance
      of their own hospitals.

PMID- 16294675
TI  - Bioterror events: preemptive strategies for healthcare executives.
AB  - Today's healthcare executives face challenges that their predecessors have never
      known: bioterror events. To prepare their organizations to cope with new and
      emerging strategic threats of bioterrorism, these executives must consider
      preemptive strategies. The authors present courses of action to assist
      executives' internal, external, and cross-sectional organizational preparedness.
      For example, stakeholder groups, internal resources, and competencies that
      combine and align efforts efficiently are identified. Twelve preemptive
      strategies are provided to guide healthcare executives in meeting these
      formidable and unprecedented challenges. The reputation of the healthcare
      organization (HCO) is at risk if a bioterror event is not properly handled,
      resulting in severe disadvantages for future operations. Justifiably, healthcare
      executives are contemplating the value of prioritizing bioterror preparedness,
      taking into account the immediate realities of decreasing reimbursement,
      increasing numbers of uninsured patients, and staffing shortages. Resources must
      be focused on the most valid concerns and must maximize the return on investment.
      Healthcare organizations can reap the benefits of a win-win approach by
      optimizing available resources, planning, and training. Bioterror preparedness
      will transcend the boundaries of bioterrorism and prepare for myriad mass
      healthcare incidents such as the looming potential for an avian (bird) influenza
      pandemic.

PMID- 16294676
TI  - The identification of high-cost patients.
AB  - The authors examine whether retrospective claims data are useful to distinguish
      future high-cost cases among the uninsured. They rely on internal claims and
      accounting data for the calendar years from 1999 to 2001 from a representative
      safety net facility to describe the distribution of costs and any characteristics
      that distinguish high-cost patients from other uninsured patients. They conclude
      that administrative data combined with in-depth survey information could be a
      useful approach for identifying cases for intensive case management.

PMID- 16294678
TI  - Physician entrepreneurs and general acute-care hospitals--part 1.

PMID- 16294677
TI  - Transforming hospital board meetings: guidelines for comprehensive change.
AB  - Does the following remind you of a hospital board meeting you attended recently?
      The meeting starts late, the PowerPoint presentation on hospital operations is
      too detailed to understand, 20 minutes are spent discussing parking, one or two
      trustees do all the talking, others check their PDAs or scribble on the agenda,
      and you try to keep your mouth shut while yawning. Hospital board meetings are
      often described as ritualized, unfocused, rambling, mindless, and inconclusive.
      Experts agree that board meetings in many hospitals are dysfunctional and need
      restructuring (Knecht 2001; Perrine 2003; Orlikoff and Totten 2002). Recently,
      St. Joseph Hospital in Orange, California, employed consultants and invested much
      effort in making its board meetings productive (Perrine). More such endeavors are
      needed for better hospital governance. In the last 5 years, several books and
      articles have focused on reforming board meetings. In this article I draw on them
      to discuss key problems of board meetings and how to make the meetings more
      effective.

PMID- 16294679
TI  - Patient-physician relationships in the managed care environment--a comparative
      analysis of various models.

PMID- 16294680
TI  - Bumping along to better health.

PMID- 16294681
TI  - In-home family therapy: indicators of success.
AB  - In this study, we explore how specific individual, family, and family-within
      community characteristics, as well as aspects of in-home family therapy, relate
      to responses to treatment. The Child and Adolescent Functional Assessment Scale
      scores and Global Assessment of Functioning scores were used as outcome measures.
      Results revealed significant differences between pre- and post-scores for clients
      receiving in-home family therapy services, providing an initial indicator of
      treatment success. In addition, primary family caregiver social support, role
      performance in school/work, and self-harmful behavior were indicative of
      successful outcomes. Clients with higher problem levels had the greatest rates of
      change, and clients receiving more hours of services fared better in therapy.

PMID- 16294682
TI  - An investigation of unmet intimacy needs in marital relationships.
AB  - In this investigation we examined partners' responses to unmet intimacy needs in
      hopes of better understanding how these responses may affect intimacy
      satisfaction and overall relationship satisfaction. Eighty-four married couples,
      plus four additional husbands and 12 additional wives, were recruited from the
      community and completed measures of relationship satisfaction, intimacy need
      satisfaction, and attributional and communication responses to unmet intimacy
      needs. Consistent with the proposed mediational model, less negative
      attributional and communication responses to unmet intimacy needs were found to
      be beneficial for overall intimacy satisfaction and relationship satisfaction. In
      addition, more positive communication responses contributed to greater intimacy
      satisfaction. Limitations and clinical implications of the current study and
      directions for future work are discussed.

PMID- 16294683
TI  - Family-directed structural therapy.
AB  - Family-Directed Structural Therapy (FDST) is an approach to family therapy built
      on traditional concepts of Structural Family Therapy, the Strengths Model, and
      Group Work Theory. The FDST approach is a goal-oriented, time limited approach
      that enables the family to identify strengths and areas of concern, as well as to
      enhance family functioning. This process is facilitated via the use of a common
      vocabulary and a concretely organized, easily administered FDST Assessment Tool
      that is completed by adult family members. This article presents the essential
      features of the FDST approach, including the use and scoring of the FDST
      Assessment Tool. It concludes with an extensive case example.

PMID- 16294684
TI  - Spiritual assessment in marital and family therapy: a methodological framework
      for selecting from among six qualitative assessment tools.
AB  - Emerging professional and cultural developments underscore the importance of
      spiritual assessment. Most marriage and family therapists, however, appear to
      have received little training on the topic. Consequently, this article overviews
      a complementary family of six recently developed qualitative assessment
      approaches or tools, an initial brief assessment tool and five comprehensive
      assessment tools, and presents a methodological framework for using the six
      tools. To help decide whether or not a comprehensive assessment is warranted
      after conducting an initial brief assessment, two general guidelines are offered.
      Suggestions for selecting the appropriate comprehensive assessment tool are also
      presented, and summarized graphically in the form of a decision tree. The overall
      methodological framework is designed to be congruent with the recent spiritual
      assessments recommendations issued by the Joint Commission on Accreditation of
      Healthcare Organizations (JCAHO), the largest healthcare accrediting organization
      in the United States.

PMID- 16294685
TI  - Integrative module-based family therapy: a model for training and treatment in a
      multidisciplinary mental health setting.
AB  - Thirty years ago, leaders in psychiatry expressed hope for more interdisciplinary
      collaboration with family therapy. Since then marriage and family therapy (MFT)
      has entered the mainstream of clinical practice in psychiatry and psychology. It
      is mandated for training in psychiatry and psychology. We propose a model for
      collaboration, training, and treatment in interdisciplinary mental health
      settings that strives to integrate empirical bodies of knowledge in MFT,
      psychiatry, and psychology and to provide a usable and testable clinical approach
      to treatment. It can be taught to trainees with various or limited training in
      MFT This model delineates nine critical domains that guide treatment. Flexibility
      is central to this model, focusing on techniques and clinical methods based on
      empirically supported treatments, when available, and best-practice standards.

PMID- 16294686
TI  - An interactional model of questions as therapeutic interventions.

PMID- 16294687
TI  - Family therapy as a dialogue of living persons: a perspective inspired by
      Bakhtin, Voloshinov, and Shotter.
AB  - There are not a lot of conceptual tools that can help a family therapy teacher to
      talk and teach about the importance of the therapeutic relationship in family
      therapy practice. The idea that family therapy can be conceived as a dialogue
      might offer a fresh and promising perspective. Mainly inspired by the work of
      Bakhtin, Voloshinov, and Shotter, the author considers if the concept of dialogue
      can help us to talk about something that is there all the time in our family
      therapeutic practices, although sometimes unnoticed, and that is hard to talk
      about because we lack the necessary conceptual tools. When we choose to
      conceptualize family therapy as dialogue, the focus of the therapist is not
      primarily on data collection, information processing or problem analysis. The
      therapist is not primarily concerned with knowing, or with not-knowing. Instead,
      the focus is on the idea that first and foremost therapy is a meeting of living
      persons, searching to find ways to share life together for a while. Clinical
      vignettes that feature children's drawings in family therapy are used as
      illustrations.

PMID- 16294688
TI  - Raising multiracial awareness in family therapy through critical conversations.
AB  - Multiracial families are uniquely affected by racial dynamics in U.S. society.
      Family therapists must be prepared to meet the needs of this growing population
      and to support racial equity. This article includes an overview of literature
      related to being multiracial and offers a framework for working with multiracial
      identity development in therapy. A critical conversation approach to working with
      multiracial identity is shared along with case examples. The authors' experiences
      developing the model via a practitioner inquiry group are highlighted.

PMID- 16294689
TI  - [Results of the reconstruction of small sensory nerves defects with autologous
      vein conduits].
AB  - Sural nerve grafting for the reconstruction of small defects of sensory nerves is
      associated with relatively considerable donor site sacrifice which is loss of
      sensation on the lateral side of the foot. One of the alternative and accepted
      methods of reconstruction of nerve gaps is bridging with autologous vein conduit.
      Material and methods. Thirty-two patients with post-traumatic sensory nerve gaps
      within the hand and forearm were operated on by vein grafting. Twenty-ones were
      operated as elective and 11 in emergency. Nerve defect was 1-2 cm long in all
      patients. In seven patients a painful neuroma within the damaged nerve was
      present. The results were assessed mean of 8 months after surgery. Two-point
      discrimination test and light touch threshold test were performed. Results.
      Twenty-five patients were available for final examination. None of them recovered
      normal threshold of the light touch (press with 0.07 g filament). Eleven patients
      (44%) could feel touch with 0.2 g filament, seven patients (28%) with 2 g
      filament and seven with 4 g filament. Six patients (24%) restored two-point
      discrimination 6 mm, twelve (48%) achieved 10 mm, four (16%) achieved 15 mm, and
      three had worse than 15 mm. Regarding satisfactory recovery of the sensation at
      the level of 10 mm two-point discrimination and 2g threshold of the light touch,
      these results were noted in 18 patients (72%). Presented outcomes as well as
      review of the literature allows us to conclude that vein grafting of the sensory
      nerve defects of 2 cm or less is a reasonable solution which is worth to apply in
      any clinical situation.

PMID- 16294690
TI  - [The teardrop development after conservative treatment of developmental dysplasia
      of the hip].
AB  - The purpose of the study was to evaluate the development of the teardrop in
      children from the time of the initial diagnosis of DDH to skeletal maturity and
      asses if width, shape and type of teardrop were associated with final results.
      Anteroposterior pelvis radiographs of sixty eight patients (64 girls and 4 boys)
      with unilateral dislocation of the hip treated with closed reduction were
      reviewed retrospectively. The average age of children at the time of initial
      diagnosis was 13,4 months (range from 5 to 32 months), and at final follow-up
      minimum 14 years (average 23 years). At the time of initial diagnosis teardrop
      was seen in 66% normal and 21% dislocated hips. The width of acetabular floor and
      superior width of teardrop were greater in dislocated hips. Five months after the
      reduction and at the age of 6 to 8 years teardrop was observed with similar
      frequency in both groups. In treated hips widening of acetabular floor and
      superior part of teardrop was still present. The V shape was detected more often
      in primary dislocated hips at the age of 6 to 8 years and these hips were usually
      classified as fair or poor according to Severin class at skeletal maturity. There
      was no relationship between the type of teardrop and the final results. The
      continued presence of V shaped teardrop, widening of superior width of the
      teardrop and thickening of the acetabular floor are suggestive of residual
      dysplasia.

PMID- 16294691
TI  - [Septic loosing of hip and knee prosthesis].
AB  - Loosening of an artificial joint is a common complication in orthopedic surgery.
      It is estimated that bacteriological implant contamination is responsible for its
      loosening in 2-5 percent of cases, and in most cases aseptic loosening takes
      place. Despite low percentage of positive microbiological studies,
      histopathological examinations and modern laboratory techniques, including PCR
      (Polymerase Chain Reaction) allow to diagnose the bacterial contamination of the
      loose implant to ca 70 percent. Those observations point out to the high
      coincidence of bacterial contamination with implant loosening strongly suggesting
      its influence on activation of the inflammatory process destabilizing an implant.
      But the question, why in those cases bacterial contamination does not lead to
      clinically obvious suppuration, remains unknown. The possibility to activate the
      immune system by the subcellular elements of the bacterial cells leading to
      persistent inflammation with granulation tissue formation is likely. Presented
      paper discusses the process of orthopedic prosthesis loosening, the role of
      bacterial contamination in it. and the newest techniques for their examination.

PMID- 16294692
TI  - [Osteogenesis imperfecta--lower limb in osteogenesis imperfecta].
AB  - The author of this paper asses lower extremity in 141 children with osteogenesis
      imperfecta, treated in University Children Hospital in Krakow in years 1988-2002:
      number of fractures, presence of the deformation, radiological findings,
      possibility of walking. Only 3 from this group did not suffer from lower
      extremity long bone fractures. In remaining patients, the number of fractures was
      4 on average with type I and IV, and 46 fractures in children with type III
      osteogenesis imperfecta in each patient. Perinatal fractures appeared in 26
      children with type II or III oi. In remaining, first fracture happened at the age
      of 23 months on average. 21% of the children had never walked before, and the
      rest of them started pionisation at the age of 20 months on average. Lower
      extremities deformations appeared in 113 children (80%). We assessed typical
      deformity pattern, based on clinical and radiological findings: varisation of
      femur and antecurvation of the tibia. The movement limitations in hips or knees
      was found in 29 children. Radiological changes in growth cartilage, so-called
      "popcorn calcification" were found in 15 children with type III of osteogenesis
      imperfecta.

PMID- 16294693
TI  - [Osteogenesis imperfecta--operative treatment on lower extremities in children
      with osteogenesis imperfecta].
AB  - The group of 141 children with osteogenesis imperfecta was treated in Orthopaedic
      Department of the University Children Hospital in Krakow, Poland. In 77 (54.6%)
      children from this group, we operated on lower extremities. Prophylactic
      operations, that were intramedullary Rush rodding, we performed in 19 cases (14
      femurs and 11 tibias). Sofield-Millar procedures we performed in 58 children. We
      operated 321 times - there are 4 operations on average in one child. Average
      follow-up period was 6.7 years. We operated 473 long bones: 234 femurs and 239
      tibias. We did 479 osteotomies. First operations were done at the age of 9 years
      on average (1.5-21 years). Further operations, 3 in each patient on average, we
      performed in period 37 months from one to another on tibias and 49 months on
      femurs. In all operated children we achieved full axis correction and their
      activity after operation improved. In order to assess that, we used the Bleck
      scale. In general, before operation, 54 (70%) children did not walk, and, in
      contrast, after operations 53 (69%) started walking. Operative treatment of the
      lower extremities in children with osteogenesis imperfecta improves their
      clinical physical abilities, quality of life and allows increase in activities.

PMID- 16294694
TI  - [Operative management of long-bone of the upper limb in children with
      osteogenesis imperfecta].
AB  - The authors present their own experiences in operative treatment of the upper
      extremities in 24 children with osteogenesis imperfecta (oi) among 141 treated in
      years 1988-2002, in whom 34 operations were performed. In one subgroup were
      children presented with bone fractures: olecranon six, humerus shaft five,
      lateral condyle of the humerus one, humerus supracondylar fracture one. In second
      subgroup included children with upper limb deformities following procedures were
      performed: correction of cubitus varus three, humerus osteoclasis two, dislocated
      radial head resection, forearm correction thirteen. Results after operative
      management of fractures were very satisfying for all the children--proper
      fracture healing, axis of the bones was straight and a full mobility of the
      joints was achieved. In second group: partial deformation recurrence after
      cubitus varus correction, good result on the one side and lack of correction an
      the other after humerus osteoclasis; bad result in terms of elbow mobility after
      radial head resection; good results (despite complicated healing and wires
      migration) in terms of axis correction after forearm bones osteotomies. Surgery
      of the upper limbs in osteogenesis imperfecta is very challenging but it is worth
      to perform, as it improves function.

PMID- 16294695
TI  - [Neuropathy of the obturator nerve as a source of pain in soccer players].
AB  - Chronic inguinal and lower abdominal pain in high-performance athletes is common
      and often disabling problem. Diagnose and treatment is often difficult due to
      many anatomic structures in the inguinal and groin region that have the potential
      to cause pain. We report 52 cases of a chronic groin pain in soccer players due
      to fascial entrapment of the obturator nerve. All patients presented clinical
      symptoms and signs of post exercise groin, lower abdominal or medial tight pain
      and adductor muscles weakness and paresthesia in cutaneous distribution of medial
      thigh. Except clinical signs in the diagnosis of obturator neuropathy we used
      diagnostic local anaesthetic block and electromyography. In 52 patients the cause
      of chronic groin pain was obturator neuropathy and they were treated operatively.
      Surgical neurolysis provided the definitive cure of pain in 41 players.

PMID- 16294696
TI  - [Correlation between the content of transforming growth factor-beta 1,
      interleukin-1 beta and collagenase activity in proximal femur bone samples
      obtained from patients with femoral neck fracture].
AB  - The aim of this study was to determine correlations between the content of TGF
      beta1, IL-1beta and collagenase activity in bone samples of the femoral neck
      obtained from patients with femoral neck fracture. The material consisted of 42
      samples of cancellous bone of femoral neck collected during hemiarthroplasty or
      total hip replacement procedure. 24 samples of cancellous bone from patients with
      osteoarthritis of the hip harvested during total hip replacement served as a
      control group. The content of TGF-beta1, IL-1beta was measured using ELISA and
      collagenase activity was measured with spectrofluorometry. In patients with
      fracture there was found a distinct inversely proportional correlation between
      the content of TGF-beta1 and IL-1beta. This correlation was not observed in the
      control group. In addition, a directly proportional relation between the content
      of TGF-beta1 and IL-1beta was discovered. These results confirm mutual
      correlations between examined cytokines in bone.

PMID- 16294697
TI  - [Comparison of cost-effectiveness in knee arthroscopy performed under local,
      general intravenous and spinal anesthesia].
AB  - The study was performed to compare cost-effectiveness between local, regional
      (epidural) and general i.v. anesthesia in outpatient knee arthroscopy. The 520
      outpatient diagnostic arthroscopy were performed in witch 443 underwent operative
      part. The cost of ambulatory surgery unit was 900 PLN/hour, postanesthesia care
      unit and care unit 315 PLN/hour each. The cost of local anesthesia 39 PLN,
      regional one 44 PLN and general one 58 PLN. The total cost of arthroscopy
      performed in local anesthesia, general and regional ones were respectively 1264,
      1296 and 1567 PLN. Local anesthesia in 520 arthroscopies produces savings of
      16667 and 157877 PLN comparing to general anesthesia and regional one. The
      biggest part of the costs in all types of anesthesia was ambulatory surgery unit
      cost and postanesthesia care unit cost which appears only in epidural anesthesia.

PMID- 16294698
TI  - [Estimation of twenty days treatment of neck pain by McKenzie method].
AB  - The aim of our study was to define the most common reasons for chronic neck pain
      and to state a connection between correction of posture by McKenzie and the
      character of pain. We investigated 30 people with chronic neck pain. They were
      patients of Out-Patients Unit of Rehabilitation. The average age was 43 +/- 6.
      Our group consisted of 21 women and 9 men. We used McKenzie protocol as a basis
      on the beginning and the end of treatment. The most important reason of neck pain
      in this study was frequent flexion of the neck and long-lasting flexion position.
      Pain often was activated by flexion and rotation of the neck. Above 70% of our
      patients stated that a character of pain changed towards better profile. Method
      of McKenzie is looked a quite successful in a correction of a posture of the body
      itself. Probably this method is capable to resolve a large portion of neck-pain
      problems. It should be used more frequently in clinical practice.

PMID- 16294699
TI  - [What's new in fracture treatment at the beginning of the 21st century?--part I].
AB  - We decided to instruct ourselves of the scientific world literature at the
      beginning of the 21st century regarding the treatment of fractures. We wanted to
      convince ourselves if there is a real progress in this area. In the following
      chapters concerning particular body regions we present the contemporary
      experiences in the diagnostics, treatment, visible tendencies and directions of
      the development.

PMID- 16294701
TI  - Prevalence of physical activity levels by ethnicity among adults in Hawaii, BRFSS
      2001.
AB  - BACKGROUND: Few studies have examined the differences in physical activity levels
      between subgroups of Asian or Pacific Islanders living in the United States. This
      study compared levels of physical activity for three subgroups of Asian or
      Pacific Islanders residing in Hawaii. METHODS: Data on Native Hawaiian/Part
      Native Hawaiian (N=585), Filipino (N=548), Japanese (N=871), and White (N=1728)
      adults were obtained from the Hawaii 2001 Behavioral Risk Factor Surveillance
      System (BRFSS), which contained more detailed questions on ethnicity than are
      collected by most states. Six physical activity categories were compared:
      inactive, insufficient (some activity but less than recommended activity),
      moderate activity (> or = 30 minutes of moderate activity > or = 5 days a week),
      vigorous activity (> or = 20 minutes of vigorous activity > or = 3 days a week),
      recommended activity (meeting either moderate or vigorous activity requirements),
      and a recently suggested target of > or = 60 minutes of moderate activity 7 days
      a week or > or = 20 minutes of vigorous activity > or = 4 days a week. RESULTS:
      Among Asians or Pacific Islanders, Native Hawaiians/Part Native Hawaiians were
      most active (38.9% moderate and 23.9% vigorous), followed by Japanese (32.1%,
      20.4%) and Filipinos (31.8%, 18.6%). Whites were more active than any of these
      three subgroups (47.2%, 35.4%). CONCLUSIONS: Differences in physical activity
      levels between subgroups of Asians or Pacific Islanders in Hawaii suggests that
      aggregated data for all subgroups obscures important information about
      disparities in activity levels. State efforts to reduce disparities in activity
      levels should take into account differences between Asian or Pacific Islander
      subgroups.

PMID- 16294702
TI  - Giant basal cell carcinoma: report of two cases and review of risk factors.
AB  - GBCCs are rare, tend to be multiple, often develop in sun-protected areas,
      usually occur in Caucasians without a family history of skin cancer, and have no
      clear association with immunological or psychiatric factors. Fear may be the
      underlying factor leading to neglect and chronicity of the tumors.

PMID- 16294700
TI  - Excellence in research and education at the John A. Burns School of Medicine: a
      tribute to Edwin Cadman's vision.

PMID- 16294703
TI  - [Steps toward a "European child and adolescent psychiatry"].

PMID- 16294704
TI  - [Autism and metabolic disorders-a rational approach].
AB  - The causes of autism are heterogeneous and predominantly genetically determined.
      An exact aetiology is found in less than 10% of affected patients. The
      disappointment about low rates of success in identifying a definite pathology,
      numerous reports about the association of autism and "metabolic derangements",
      and rumours of "miraculous cures" after application of various drugs and dietary
      regimes have resulted in substantial confusion about meaningful diagnostic
      procedures and rational therapies for subjects with autism. The aim of this
      report is to give an overview about rare, genetically determined neurometabolic
      disorders (inborn errors of metabolism) that are evidently (e.g. Smith-Lemli
      Opitz Syndrome) or allegedly (e.g. succinate semialdehyde dehydrogenase
      deficiency) associated with autism-specific symptoms. Affected patients usually
      display additional neurological symptoms. Procedures required to establish the
      diagnosis and eventual therapeutic consequences derived from a specific metabolic
      defect are presented. In addition to these well-defined neurometabolic disorders
      for which there are rational therapeutic strategies, hypotheses about the
      association of autism with "metabolic derangements" that could not be confirmed
      or were clearly falsified are discussed.

PMID- 16294705
TI  - [Alcohol consumption in adolescence--social and individual influential factors].
AB  - OBJECTIVE: To examine the influence of several social and individual factors on
      adolescent alcohol consumption. METHODS: A prospective longitudinal study was
      carried out to investigate the mental development from birth to adolescence in a
      cohort consisting originally of 384 children. Six different variables were
      assessed: alcohol consumption at the age of 16 years, sensitivity to alcohol,
      temperament, peer influence, parental educational behaviour, and mental
      disorders. RESULTS: The majority of adolescents (97%) consumed alcohol, 24% did
      so at least once a week. Social factors (like negative peer influence or parental
      educational behaviour) and individual factors (like sensitivity to alcohol,
      temperament or mental disorders) predicted the amount of alcohol consumed per
      month at the age of 16 years. CONCLUSIONS: Early identification of at-risk
      adolescents appears to be essential. Successful preventive strategies include
      support for parental education, reduction of negative peer influence, and
      training in order to enhance one's perception of one's own body and sensitivity
      to alcohol.

PMID- 16294706
TI  - [Encopresis--predictive factors and outcome].
AB  - OBJECTIVES: comparison of diagnostic, clinical and therapeutic features and their
      predictive value for the outcome of encopresis in children and adolescents.
      METHODS: 85 children and adolescents (aged 9.6 +/- 3.2 years) with severe
      encopresis (ICD 10: F98.1) were investigated during inpatient treatment and 35 of
      them again 5.5 +/- 1.8 years later. Mentally retarded patients were excluded.
      Inpatient therapy consisted of treating constipation and/or stool regulation by
      means of laxatives, behavioural approaches, and the specific therapy of comorbid
      psychiatric disorders. RESULTS: During inpatient treatment 22% of the patients
      experienced total remission, 8% an unchanged persistence of symptoms. Of the 35
      patients studied at follow-up 5.5 years later, 40% were symptom-free. As main
      result, prognostic outcome depended significantly on sufficient treatment of
      obstipation. Another important factor was the specific therapeutic approach to
      psychiatric comorbidity, especially to ADHD. The outcome for patients with
      comorbid ICD 10: F43 was significantly better than for the other patients. Those
      who were symptom-free at discharge had significantly better long-term outcomes.
      CONCLUSIONS: Decisive to the success of encopresis treatment were the stool
      regulation and the specific therapy of associated psychiatric illnesses, in
      particular of ADHD. Inpatient treatment revealed significantly better long-term
      outcomes where total remission had been achieved by the time of discharge from
      hospital.

PMID- 16294707
TI  - [Do different survey settings influence the prevalence of symptoms? A
      methodological comparison using the Youth Self-Report].
AB  - OBJECTIVES: The self-reported emotional and behavioural disorders among
      adolescents were assessed by the Youth Self-Report (YSR). The YSR was
      administered either in households or in classrooms. The goal of the study was to
      prove whether these different settings affect the prevalence rates of symptoms
      reported in the YSR. METHODS: Mean scores and standard deviations of problem
      scales of two classroom samples and one household sample that was generally used
      as a reference were compared. The data were also compared with two classroom
      samples from Sweden and Greece. Statistical analyses were performed by means of t
      test (unpaired), the evaluation of the magnitude of the effects by means of
      Cohen's criteria. RESULTS: Classroom samples detected a significantly higher
      prevalence of symptoms than did household samples. This is the case for almost
      all of the problem scales in the YSR. The result of our study supports the
      finding that the setting of surveys that use self-administered questionnaires in
      classrooms themselves affect the prevalence of self-reported symptoms assessed by
      the YSR. CONCLUSIONS: The results of surveys may be influenced, to a much greater
      degree than previously thought, by the settings in which they are administered.
      Further research is needed to identify the specific influences that differ for
      surveys administered at home, respectively at school.

PMID- 16294709
TI  - Tree of heaven may be hard on the heart.

PMID- 16294708
TI  - [Emotional and behavioral disorders at preschool age--results of a study in
      kindergarten children in Dortmund using the Caregiver-Teacher Report Form C-TRF/1
      1/2-5].
AB  - OBJECTIVES: Currently there is a lack of screening instruments suitable for use
      by preschool and kindergarten teaches to assess behavioural and emotional
      problems in preschool children. The C-TRF/1 1/2-5 (Caregiver-Teacher Report Form
      for the ages 1 1/2-5) is a screening instrument designed by Achenbach to assess
      behavioural and emotional problems in this age group. In a joint project of the
      Fachhochschule Dortmund and the Department of Child and Adolescent Psychiatry,
      University of Ulm, in cooperation with the Youth Welfare Office Dortmund, the C
      TRF/1 1/2-5 was used to assess the prevalence of psychological disturbance among
      kindergarten children. METHODS: 1,050 children aged 3-6 years from 46
      kindergartens from the greater Dortmund urban area were rated by their caregivers
      on the basis of the German version of the C-TRF/1 1/2-5. RESULTS: The reliability
      of C-TRF/1 1/2-5 proved to be good-to-sufficient, with internal consistencies
      ranging from .94 to .58. The number of behavioural and emotional problems, which
      is very close to that found among American preschool children, decreases with age
      and more strongly so among girls. The externalizing problems among boys do not
      decrease much, but remain quite stable from age 3 to age 6. The prevalence of
      internalizing problems among preschool boys and girls does not differ.
      CONCLUSIONS: The German version of the C-TRF/1 1/2-5 proved to be an instrument
      sufficiently reliable for screening behavioural and emotional problems in
      preschool children. The prevalence of these psychological problems among German
      and American children is very similar.

PMID- 16294710
TI  - [Modeling for activating peripheral nerves by transverse electric field].
AB  - The classical cable function has been used to represent the response of
      peripheral nerves stimulated by external parallel electric field. It can not
      describe the excitation of peripheral nerves stimulated by perpendicular electric
      field. In this paper, responses of the nodes of Ranvier to transverse-field are
      deeply investigated by mathematic simulation and in-vitro experiments. The paper
      demonstrates that, under perpendicular electric field stimulation, the responses
      evoke a two-stage process including an initial polarization and the actual change
      of the transmembrane potential. It is the net inward current along a radial
      direction of the node of Ranvier that causes the peripheral nerve excitation.
      Based on the two-stage process, a novel model is introduced to describe
      peripheral nerves stimulated by transverse-field, and the classical cable
      function is modified. The new model and the improved cable function are verified
      by several in-vitro experiments. They can be used to represent peripheral nerves
      responses by arbitrary electric field stimulation.

PMID- 16294711
TI  - [A bipolar optocoupler isolation amplifier with high precision and wide
      bandwidth].
AB  - To fit the technological requirements in electrical impedance tomography system,
      an improved bipolar optocoupler isolation amplifier based on single analog
      optocoupler was realized. The experimental results illustrates that the full
      power -3dB bandwidth of this circuit is greater than 800 KHz, the equivalent
      output noise is lower than 50 uV(RMS), and the linearity at +/- 4 V inputs is
      lower than 0.01%. In addition to these features, the circuit also have the
      advantages of simple structure and no distortion caused by mismatch between
      analog optocouplers.

PMID- 16294712
TI  - [The segmentation of eye socket].
AB  - In this paper, we propose a hybrid level set model with application to the
      segmentation of eye socket. Compared with other level set methods, the hybrid
      model is more robust and accurate due to the combination of region and boundary
      information. It solves the leaking problem of boundary based level set method.
      The segment results of hybrid level set model can be used in 3-D eye socket
      reconstruction and calculation of hydroxyapatite implant, which are useful in
      computer-aided surgery. Experiments have shown that hybrid level set model has
      very good performance in the segmentation of eye socket.

PMID- 16294713
TI  - [A 3D tomography technique based study on event-related potential in attention].
AB  - In this paper the event-related potential (ERP) of selective attention to the
      left and right visual field is investigated with 3D tomography technique. The
      results show that compared with the scalp surface ERP data, the current source
      intensity derived from tomography can better reflect the enhanced effect of P1
      and N1, especially N1. Moreover, C1 component can be observed in the results,
      which cannot be identified in the scalp data.

PMID- 16294714
TI  - [Synchronization of the activity of gamma oscillation and ERP components].
AB  - In the present study the activity of the gamma oscillation synchronized with the
      stimuli and ERP is investigated by means of unimodal and bimodal experiments. The
      multiresolution wavelet algorithm is used for signal extraction and Gabor
      transform is employed to represent the temporal evolution of the selected
      frequency components. The results show that the gamma oscillation is strongly
      phase-locked not only with the exogenous stimuli in the three experiments, but
      also with the endogenous components of ERPs (N2b, P300). And the ERP and the
      gamma oscillation induced by the bimodal stimuli show the audio-visual bisensory
      integration and relationship. In addition, the results from the experiments with
      the auditory stimuli show that the gamma oscillation may be closely related to
      the perception of auditory signals.

PMID- 16294715
TI  - [Positioning path planning for HIFU Surgery Platform application].
AB  - Based on the analysis of the workspace and positioning procedure for using the
      HIFU Surgery Platform, a simplified representation of the tumor volume's location
      and orientation in the workspace by Positioning Volume Ellipsoid is proposed. The
      terminal and intermediate configuration which the ultrasound focus must pass
      through during positioning is determined; according to the decided
      configurations, a C2 continuous uniform interpolating B spline positioning path
      is constructed in Lie Group SE (3); and a case analysis is made at last.

PMID- 16294716
TI  - [Experimental study of the lethal effects of steep pulsed electric field on
      cancer cells in BALB/c mice].
AB  - This study was conducted to observe the lethal effects of steep pulsed electric
      field(SPEF) on the cancerous squamous cells in BALB/c mice. Female mice were
      inoculated with the solution of cervical cancer cells line. The tumor-bearing
      mice of the experiment group were exposed to SPEF. Then, the histomorphological
      changes were examined and compared between experiment group and control group.
      The histological and antitumor assay showed that SPEF could selectively injure
      tumor cells and inhibit cell proliferation. After treatment, pyknosis,
      karyoclasis and karyolysis of cancer cells were observed under light and electron
      mircroscope. More serious changes appeared some days later. These results
      indicate that SPEF have lethal effects on cervical cancer. It may prolong the
      survival period of tumor-bearing mice.

PMID- 16294717
TI  - [The simulation of SAR and temperature distribution and parameters analysis for
      tumor RF thermotherapy].
AB  - In this paper are reported the model establishment and numerical simulation of
      specific absorption rate(SAR) and the unsteady temperature distribution for the
      non-invasive tumor RF thermotherapy. The model can correctly reflect the
      attenuation of electromagnetic wave in the biotissue, the variation of perfusion
      with temperature and lower perfusion of the tumor tissue are fully considered in
      the simulation. These measures made simulation results more close to the clinical
      results. Also presented in the paper are detailed analyses and discussions on the
      characteristics of SAR of electromagnetic energy and the temperature profiles,
      the effects of the frequency and the perfusion on the depth for effective
      treatment. The simulation results are of great significance for directing the
      clinical application of tumor RF thermotherapy.

PMID- 16294718
TI  - [Study on feature extraction of the sleep-multigraph].
AB  - Recording the sleep-multigraph is an important method for sleep monitoring and
      research. In this study, after the all-night sleep in six nights being monitored,
      the process of sleep is shown by EEG complexity and spectrum feature. It can
      provide a new path for estimating the sleep quality by sleep staging. Especially,
      the EEG complexity in different sleep stages is studied. The results indicate
      that the deeper the sleep, the smaller the EEG complexity of whole cortex. This
      is of significance to the study on sleep biopsychology.

PMID- 16294719
TI  - [Synergic pattern analysis of upper limb grasping movements].
AB  - In order to discuss the evaluation method of human upper limb movements, the
      patterns of movement coordination during healthy people prehension have been
      researched. Eight subjects were asked to perform different reaching-grasping and
      drinking water from the cup tasks with different indices of difficulty, and the
      arm movement trajectories and the main muscles group electromyography (EMG) data
      were collected. To explore the prehension control mechanism, a comparison has
      been made between the solution of the theoretic calculation and the experimental
      data. The results show that the topological invariance was observed in the
      trajectories of different task performance, and the linear relationships between
      joints covariation were exhibited. Moreover, the different muscles were
      controlled and combined into units of synergistic muscular group necessary to
      reach and grasp the goal.

PMID- 16294720
TI  - [Electrochemotherapy and its mechanism for sarcoma of KM mice].
AB  - In this paper are analyzed the effect of electrochemotherapy and its mechanism.
      The favorable parameter of electric pulses (EP) was studied in vitro using the S
      180 cells exposed to various EP. After the tumor model was copied, the tumor
      bearing mice were randomly divided into four groups: control, chemotherapy,
      electrotherapy, and electrochemotherapy. The tumor inhibitory ratio, the cure
      ratio and the level of oxygen free radicals (OFR) were determined. The inhibitory
      ratio and cure ratio of electrochemotherapy group were significantly higher than
      those in the chemotherapy, electrotherapy and control groups (P < 0.05). The
      injury of OFR was decreased while the immunological competence was increased. The
      mechanism of electrochemotherapy may be related with the enhancement of cell
      membranepermeability, the depression of drug resistance, the improvement of
      immunological competence, and so on.

PMID- 16294721
TI  - [An experimental study on human bitemarks digital analysis and its accuracy].
AB  - This experiment was designed to study the method of human bitemarks digital
      analysis and its accuracy. The human bitemarks were made on the dog skin by human
      dentition. The related parameters of human bitemarks and suspects criminal
      dentitions were digitally recorded and managed. The digital picture of human
      bitemark was obtained, and the dental study model, bite in wax and bitemark on
      pig skin of suspected criminal were scanned. The overlay was prepared with Adobe
      Photoshop 5. 5 and the parameters were measured with AutoCAD R14, then their
      matches were compared. The result shows that the human bitemarks digital analysis
      is a more accurate approach to human bitemarks identification. Three methods for
      collecting evidence dental study model, bite in wax and bitemark on pig skin all
      can be used as aids in forensic sciences. Dental study model is the most accurate
      one of all the three methods mentioned above.

PMID- 16294723
TI  - [Effects of He-Ne laser on gastric mucosa in rat with chronic atrophic
      gastritis].
AB  - This study sought to explore the effects of He-Ne laser irradiation on the
      gastric mucosa of experimental chronic atrophic gastritis (CAG) in rat. Fifty-two
      male adult Wistar rats were randomly divided into five groups including normal
      control group, model group and three different doses He-Ne laser groups. The CAG
      model in rats was made by administering (per gastrogavage) a compositus liquor,
      including 2% sodium salicylate and 30% alcohol, for 8 weeks to stimulate the
      rat's gastric mucosa, combined with irregular fasting and compulsive sporting as
      pathogenic factors. He-Ne laser therapy was used at different doses of He-Ne
      laser, once a day for twenty days, then the morphological changes and the
      expression of cyclinD1 were observed. Compared with untreated group, the gastric
      mucosa of 3.36J x cm(-2) He-Ne laser group was significantly thicker (P < 0.01),
      the inflammatory cells of gastric mucosa were decreased (P < 0.05), the
      morphology, structure and volume of the cells were restored or nearly normal and
      the expressions of cyclinD1 were higher (P < 0.05). In a word, small dose He-Ne
      laser (3.36 J x cm(-2)) has a good adjuvant therapeutic effect on rat's CAG.

PMID- 16294722
TI  - [Estimation of fetal weight on the basis of neural network].
AB  - The ultrasonic estimation of fetal weight at delivery is of important prognostic
      significance in obstetrical practice. The convertional regression formulas used
      for estimating fetal weight have the disadvantage of less reliability. In this
      study, we used the back propagation neural network (BP) to estimate Fetal Weight.
      Some input variables were adopted in constructing the BP model: biparietal
      diameter (BPD), cerebellum transverse diameter (TCD), abdominal circumference
      (AC), liver length (LL), femur length (FL), fetal thigh soft tissue thickness
      (FSTT), and gestational age (GA). The fetal weights of 109 singleton fetuses were
      estimated. In the training group and validation group, coincidence rates were
      89.77% and 76.19% respectively. The results show that the estimation based on
      neural network is more accurate than that by regression method. GA, its unit is
      not week but day in our formulas, is very valuable in combination with other
      ultrasonic parameters on estimation.

PMID- 16294724
TI  - [Imaging technique and clinical application of 16-slice spiral CT for coronary
      artery].
AB  - This study was conducted in pursuit of the optimal imaging technique and for a
      primary clinical application of 16-slice multislice spiral computed tomography
      (MSCT) for coronary artery. Unenhanced and contrast-enhanced 16-slice SCT imaging
      was performed in 38 cases with retrospective electrocardiographic gating. MPR,
      MIP and VRT reconstruction of enhanced scan images were made in all cases, and
      CPR, VE reconstruction images were made in some cases. The demonstration of
      coronary artery was evaluated. The influencing factors of the image quality were
      analyzed. The results showed that the detection rates of RCA, PDA, LMA, LAD, DB,
      LCX and LMB were 36 (94.7%), 34 (89.5%), 37 (97.4%), 36 (94.7%), 34 (94.4%), 36
      (94.7%), 34 (89.5%) on axial images, respectively, which were higher than those
      of the arteries on 3D images (P < 0.01). Therefore, 16-slice spiral CT is a
      reliable and accurate technique to demonstrate coronary artery and its branches,
      and is a noninvasive method to screen, diagnose and postoperatively evaluate
      coronary artery diseases. The factors influencing the image quality include the
      heart rate, the cardiac rhythm, the respiratory movement of patients and the
      trigger delays of imaging processing.

PMID- 16294725
TI  - [A study on myocardial microcirculation with coronary angiographic impulse
      response function].
AB  - We have established a digital coronary angiograph-analyzing system on the
      principle of coronary angiographic impulse response, and combined the system with
      the quantitative coronary analysis (QCA) for investigating the coronary
      microcirculation (Tmicro(-1)), the minimal stenotic diameter of coronary (MLD)
      and coronary hemodynamic parameters (mAP, CFV, Rcor) in 20 patients with coronary
      stenosis. The results showed the minimal stenotic diameter (MLD) and Tmicro(-1)
      decreased, with the increase of stenosis of proximal coronary. After successful
      percutaneous coronary intervention treatment, the Tmicro(-1) increased with the
      increase of MLD and was in linear correlation with MLD (r = 0.87, P < 0.001). In
      conclusion, The index Tmicro(-1) detected by coronary digital angiographic
      impulse response analysis system in combination with CFV and QCA would help to
      evaluate the level of integrated diagnosis of coronary lesion in regard to
      anatomy and physiology as well as to macro and microcirculation.

PMID- 16294726
TI  - [CT diagnosis of palatal malignant tumors].
AB  - To investigate CT features of palatal malignant tumors and to evaluate, CT
      diagnostic value. CT manifestations of 32 cases of palatal malignant tumors were
      analyzed retrospectively. All cases were confirmed by pathology. There were 27
      males and 5 females between 23 and 80 years of age. Axial contrast enhancement CT
      scan was performed in all cases, among them, nonenhancement CT scan was also
      performed in 8 cases and coronal CT scan was performed in 2 cases. The main signs
      of palatal malignant tumors were as follows: (1) Masses in palate in 26 cases,
      thickened palatal soft tissue in 6 cases and destruction of palate bone in 8
      cases. The lesions were located in soft palate in 22 cases, in hard palate in 4
      cases, and in the junction region between soft and hard palate in 3 cases; (2)
      Other adjacent structures and organs were involved in 27 cases; (3) Lymph nodes
      of neck metastasis were demonstrated in 17 cases. CT is an excellent technique,
      which can show the gross pathologic features and the invasion pathway of palatine
      malignant tumors, and it can provide some important information for the relevant
      clinical treatment and prognosis.

PMID- 16294727
TI  - [Analysis of HRV from brain injury by use of nonextensive relative entropy].
AB  - Due to its great clinical significance, brain injury following cardiac arrest
      (CA) has attracted more attention now. Meanwhile, there are currently no approved
      real time objective methods used to monitor brain injury following CA. In this
      study, we adopt the method of nonextensive Kullback-Leibler Entropy in
      investigating the HRV signals from brain injury and compare the result with that
      of corresponding EEG analysis. The comparative analysis shows that Kullback
      Leibler Entropy can reveal the injury level of brain following CA. And we propose
      a novel quantitative approach for monitoring brain injury.

PMID- 16294728
TI  - [Application of CWT to extract characteristic monitoring parameters during spine
      surgery].
AB  - It is necessary to monitor intraoperative spinal function in order to prevent
      spinal neurological deficit during spine surgery. This study aims to extract
      characteristic electrophysiological monitoring parameters during surgical
      treatment of scoliosis. The problem, "the monitoring parameters in time domain
      are of great variability and are sensitive to noise", may also be solved in this
      study. By use of continuous wavelet transform to analyze the intraoperative
      cortical somatosensory evoked potential (CSEP), three new characteristic
      monitoring parameters in time-frequency domain (TFD) are extracted. The results
      indicate that the variability of CSEP characteristic parameters in TFD is lower
      than the variability of those in time domain. Therefore, the TFD characteristic
      monitoring parameters are more stable and reliable parameters of latency and
      amplitude in time domain. The application of TFD monitoring parameters during
      spine surgery may avoid spinal injury effectively.

PMID- 16294729
TI  - [An algorithm for detecting T-wave alternans (TWA) based on the maximum of T
      waves].
AB  - An algorithm of detecting the TWA (T-wave alternans) based on the maximum of T
      waves transformed by FFT (Fast Fourier Transform) is described in the paper. By
      using the method we can reduce the sampling rate, which means "smaller amount of
      calculation", and solve the problem "the sampling point of T wave changes with
      the rate of heart beat". The 128 maximum values of T wave in series normal ST-T
      complex are used to carry out FFT transforms. The TWA is detected by using the
      frequency of power spectrum.

PMID- 16294730
TI  - [Coupling between adherent leukocytes and blood flow].
AB  - A theoretical model was developed to simulate the coupling between the adhered
      leukocyte and blood flow. Methods of computational fluid dynamics (CFD) were
      introduced to analyze the distributions of the shear stress and the pressure on
      the cell surface. Meanwhile, the hemodynamical parameters were measured with
      laser Doppler velocimetry. The results showed that the deformation index of the
      leukocyte was increased with initial contact angle and Reynolds number. The blood
      flow induced the redistributions of the shear stress and pressure on the surface
      of the cell, but the maximum shear stress was on the top point of the cell. It
      suggests that the non-uniform distribution of shear stress on the cell surface
      may play a particular role in the change of cell shape and functions.

PMID- 16294731
TI  - [Measuring rupture forces of P-selectin/PSGL-1 bonds using an optical trap
      assay].
AB  - Selectin/ligand interaction plays an important role in such biological processes
      as inflammatory reaction, tumor metastasis, etc. External forces affect
      dissociation of receptor-ligand bonds. A novel approach, upon optical trap
      technique, was developed in this study to investigate the dissociation of P
      selectin/PSGL-1 (P-Selectin Glycoprotein Ligand 1) bindings. Stiffness of optical
      trap was calibrated with laser power using a viscous drag method. While P
      selectin and PSGL-1 molecules were functionally coated on surfaces of glass
      beads, respectively, the dissociation of interacting molecule bond was studied by
      measuring the rupture force distribution. It was found that most probable rupture
      force increased with loading rate at < 25 pN/s. These results complemented and
      validated the current theory at low loading rates.

PMID- 16294732
TI  - [A study on cytocompatibility of poly (lactic acid) membrane modified by polymer
      microspheres with different surface charges].
AB  - Poly(lactic acid) microspheres with different surface charges have been prepared
      by using cationic, anionic or nonionic surfactants as the microspheres' surface
      stabilizers. Embedded with these microspheres, the modified PLA membranes with
      different surface charges have been obtained. The test of stability by CLSM and
      the morphological test by SEM confirmed that we obtained the microspheres
      modified PLA membranes with different surface charges successfully. The
      chondrocyte compatibility test of these modified PLA membranes showed that the
      attachment, proliferation and activity of chondrocytes on the positive surface of
      the modified PLA were better than those of other modified PLA membranes. The
      positive charge on the surface of PLA membrane could improve the cell
      compatibility of PLA well.

PMID- 16294733
TI  - [Immobilization of von Willebrand factor antibody on solid host membranes].
AB  - This study aimed at immobilizing the antibodies on the surfaces of the solid host
      membranes in order to improve the property of the biomaterial. The von Willebrand
      factor (vWf) antibodies were immobilized on the surface of Bombyx mori silk
      fibroin and PLA (Poly Lactic Acid) membrane by NH3 plasma treatment followed by
      covalent cross-linking reaction. The immobilization efficiency was evaluated by
      two methods including the antibody surplus and enzyme-linked immunosorbent assay
      (ELISA). The in vitro antithrombogenicity representing the activity of
      immobilized vWf antibody was determined by the method of Activated Partial
      Thromboplastin Time (APTT), Prothrombin Time (PT) and Thrombin Time (TT) test.
      The results demonstrate that the vWf antibodies are immobilized on silk fibroin
      and PLA membranes in an efficient way with the efficiency of antibody surplus up
      to 23.88% and ELISA reaction is positive. APTT and TT exceeded the upper limits
      distinctly, but the value of PT did not change noticeably. The in vitro
      antithrombogenicity represented the is activity-retaining form of antibodies.
      These results extend the application of antibody immobilization technique and
      provide a new idea about the design of biomaterials relating to the coagulation
      factors.

PMID- 16294735
TI  - [Hydroxyapatite nanoparticles: a novel material of gene carrier].
AB  - Hydroxyapatite nanoparticles were prepared in low Ca/P ratio by a kind of
      electrodeposition-hydrothermal process. The suspension of nanoparticles was
      cultured with SGC-7901 cells; metabolically active cells were evaluated by MTT
      analysis. Cells grew well and the nanoparticles in the concentration range of 10
      100 microg/ml had no adverse effect on the cell viability. The results show that
      the nanoparticles have excellent biocompatibility with cells. Agrose gel
      electrophoresis analysis demonstrated that the nanoparticles had the potential to
      adsorb EGFP-N1 at the pH ranging between 2 to 7. Nanoparticle-DNA complex could
      transfer EGFP-N1 into the SGC-7901 cells, and the confocal microscopy analysis
      revealed that the cells with green fluorescence showed the efficiency of
      nanoparticle uptake to be about 80% of the efficiency of the Lipofectmine TM 2
      000 uptake. In vivo, nanoparticles and DNA-nanoparticle complex were injected
      into mice respectively via tail-vein, and the mice grew well in two weeks. The
      liver, kidney, and brain of the mice were sampled and detected with electron
      microscopy, and all of these exhibited biodistribution of nanoparticles. This
      study demonstrates that Hydroxyapatite nanoparticles could be used as gene
      carriers.

PMID- 16294734
TI  - [The effect of entrapment of CpG sequence with cationic PLG nanoparticles on the
      immune responses of mice to pig paratyphoid vaccine].
AB  - Cationic PLG nanoparticles and liposome were prepared and used as package
      molecules to pack up pUC18-CpG. The effects of the packed pUC18-CpG on the
      cellular and humoral immune responses were detected in the mice that were
      inoculated with pig paratyphoid vaccine. The results showed that compared with
      the control, the amount of IgG and the titre of specific antibody were
      significantly increased in the sera of mice immunized with the CpG plasmid
      entrapped by cationic PLG nanoparticles; the proliferation and induced IL-2
      bioactivity of lymphocytes were significantly enhanced in the spleen of the
      immunized mice; the stimulatory effect of cationic PLG nanoparticles was similar
      to or stronger than that of cationic liposome. These indicated that cationic PLG
      nanoparticle could be employed as an effective package molecule to promote the
      immunostimulatory effect of pUC18-CpG.

PMID- 16294736
TI  - [Study on hydroxyapatite porous scaffold bonded by phosphates and its
      biocompatibility].
AB  - The porous scaffolds for bone tissue engineering were prepared by foam
      impregnation. The magnesium and aluminum acid phosphates were used as bonder and
      the hydroxyapatite ((Ca10 (PO4)6(OH)2, HA) powder as raw materials. Scanning
      electron microscopy (SEM) examination indicated that the 3D interconnected porous
      structure of the organic foam was replicated well by the scaffolds calcined at
      high temperature and the structural requirement of tissue engineering was
      satisfied. XRD analysis showed that the scaffold was composed of HA and
      Ca7Mg2P6O24 while calcined at 1150 degrees C for shorter time and of (Ca,
      Mg)3(PO4)2 when the time prolonged to 2 h. There was no peak of CaO found in the
      scaffolds by XRD. According to the culture in vitro, the scaffold possesses good
      biocompatibility and certain degree of degradability.

PMID- 16294737
TI  - [Biodegradation of synthetic bioglasses with different crystallinity in vitro].
AB  - SG600, SG900 and SG1100 were synthesized by the sol-gel method. Further
      treatments with increasing temperatures influenced and determined the
      crystallization degree of the material. Primary cultured osteoclasts were
      incubated for 4h and 48h on samples. Osteoclast actin labeling was examined by
      cytochemical staining. The concentrations of Ca and P in culture medium were
      quantified by colorimetric methods. SEM examined osteoclast morphology and
      resorption lacuna. Actin staining revealed on all three materials the typical
      adhesion contact ring. The Ca concentration in the culture medium of SG600 was
      significantly higher than that in control medium, SG900 and SG1100. Ca and P
      concentrations were always higher in culture media with the presence of
      osteoclasts. Morphological studies by scanning electron microsopy(SEM) showed a
      good adhesion behavior of osteoclasts on all three samples. Well-developed and
      deep resorption lacunae appearing after the osteoclastic resorption action were
      detected on all three samples. The synthetic bioglasses with different
      crystallizations caused different solubility, which seemed to have little effect
      on the osteoclast resorption behavior. The results of morphological studies on
      osteoclasts and resorption lacunae clearly demonstrate that the synthetic
      bioglasses are easily resorbed in vitro by osteoclasts.

PMID- 16294738
TI  - [Swelling characterization of poly (vinyl alcohol) hydrogel for prosthetic
      intervertebral disc nucleus].
AB  - In this study the poly(vinyl alcohol)(PVA) hydrogel elastomer was prepared by
      freezing-thawing method. The influences of percentage of poly (vinyl alcohol) in
      hydrogel, pH of solution and swelling temperature upon the swelling
      characteristic of PVA-hydrogel prosthetic nucleus material were studied. Its
      micropores were observed using SEM, and the swelling dynamics was further
      discussed. The experimental results showed that the poly (vinyl alcohol) hydrogel
      was a kind of network with a lot of micropores, the pore size was related with
      the PVA content. The maximum swelling ratio decreases when the percentage of PVA
      in hydrogel, the pH of solution and the swelling temperature were enhanced. The
      swelling process was described by the equation of swelling dynamics equation. The
      swelling rate was greatly influenced by the PVA content, the pH of solution and
      the dimension of hydrogel sample.

PMID- 16294739
TI  - [Research of the hemostasis effect of chitosan acetic acid solution].
AB  - The effect of chitosan with different molecular weight and deacetylation degree
      on blood hemostasis was tested. The experiments found evident alteration of red
      blood cell morphology and unusual coagglutination between erythrocytes in the
      anticoagulant blood which was treated by chitosan acetic acid solution. The red
      blood cells clot formation experiments showed that chitosan with low
      deacetylation degree (60%-70%) caused more red blood cells to assemble when
      compared versus chitosan with other deacetylation degrees. The effect of
      molecular weight between 10(5)-10(6) was not obvious. The thrombin time (TT),
      prothrombin time (PT), activated partial thromboplastin time (APTT), and
      concentration of fibrinogen (FIB) of blood treated by chitosan acetic acid
      solution were measured. The results proved that the hemostasis property of
      chitosan acetic acid solution was independent of the platelets and the normal
      "Cascade-like" coagulation pathway.

PMID- 16294740
TI  - [Restoring the skin from traumatism by means of collagen-konjac glucomannan
      chondroitin sulfate blend film].
AB  - This study aims at restoring the skin from traumatism by use of the collagen(from
      piglet skin) and konjac glucomannan-chondroitin sulfate blend film. The 2 cm x 4
      cm skin traumatism model was established on both sides of the waist spinal column
      in 14 New Zealand rabbits each weighing 1.5-2.0 kg. One side was covered with
      blend film, the other side was used as a control. Then the changes of the skin
      traumatism were observed at different time-points after the operation, the wound
      tissue samples were taken for histological examination. The blend film could
      prevent skin traumatism from bleeding and infection. The skin traumatism treated
      by blend film showed signs of rectangle scab and the control showed signs of
      linear scab after healing. No obvious immune rejection was seen. The collagen
      konjac glucomannan-chondroitin sulfate blend film can accelerate the restoration
      of skin from traumatism.

PMID- 16294741
TI  - [Experiment on the formation and characterizations of anodic alumina membrane for
      use in hemodialysis].
AB  - The correlations between various formation conditions and the membrane pore
      characterizations of the anodic alumina membrane were investigated for seeking
      the optimal conditions for the formation of anodic alumina membrane. High purity
      aluminum foils were used as the starting materials. The anodizations were
      conducted under three types of electrolytes, 3% sulfuric acid, 5% sulfuric acid
      and 2.7% oxalic acid, respectively, with different voltages at 0 degrees C for 48
      hours. The characterizations of the pore size, the effective porosity and the
      pore porosity were observed and determined by scanning electron microscopy. The
      hydraulic conductance of the membranes was measured to confirm that the pores
      were open and to evaluate the permselectivity of the membranes. The experimental
      results showed that the ordered pore arrays were obtained for oxidation under our
      experimental conditions. While the forming voltage was increasing, the pore size
      and pore porosity increased significantly (P < 0.05), and the effective porosity
      decreased significantly (P < 0.05). The pore size formed with 3% sulfuric acid or
      5% sulfuric acid was much smaller than that with 2.7% oxalic acid as an
      electrolyte. The hydraulic conductance of anodic alumina membrane that formed
      under our experimental condition was high than those of the membranes currently
      available in clinical procedures. The results suggested that the optimal
      conditions for the formation of anodic alumina membrane to be used in
      hemodialysis should be 3% or 5% sulfuric acid with 12.5 V to 17.5 V at 0 degrees
      C for 48 hours.

PMID- 16294742
TI  - [Influence of a new nano-root filling material on the proliferation of
      osteoblast].
AB  - This study sought to assess the effect of a new nano-root filling material, nano
      hydroxyapatite polyamide66 (nHA-PA66), on the growth of osteoblast cultured in
      vitro so as to evaluate its osteoblast-compatibility and potential to be used as
      root canal filling material. The Dulbecco's Modified Eagle Media (DMEM) leaching
      liquor of nHA-PA66 was applied to the osteoblasts of the test group while the
      DMEM itself was applied to control. The MTT assay and flow cytometry were used to
      evaluate the changes in cell growth and cell cycle. The relative proliferative
      ratio of different concentrations of nHA-PA66 ranged between 98%-106% without
      dose-dependent effect. The proportion and time of different subcycle of the two
      groups were close to each other. nHA-PA66 showed no negative effects on the
      osteoblasts' growth and cell cycle. These led to the suggestion that nHA-PA66 is
      not cytotoxic to osteoblast and is a promising material in clinical use.

PMID- 16294743
TI  - [Application of HMGN2-tag constructs to analysis of HMGN2 distribution in HeLa
      cells].
AB  - This study sought to clarify the distribution of HMGN2 in HeLa cells. The
      recombinant eukaryotic expression vectors pcDNA3. 1-myc-his-HMGN2 and pEGFP-N1
      HMGN2 were constructed, and then were transfected into HeLa cells.
      immunocytochemistry staining indicated that HMGN2 were present not only in HeLa
      nucleus but also in the cytoplasm. The presence of HMGN2 was also detected in the
      culture supernatant by ELISA with rabbit anti-serum against HMGN2 and mouse anti
      His6 monoclonal antibodies. The confocal microscope observation showed the same
      subcellular localization as that of immunocytochemistry staining. There results
      suggested that HMGN2 could be present in the nucleus and cytoplasm of HeLa cell
      as well as in the extracellular environment.

PMID- 16294744
TI  - [The role of caveolae in shear stress-induced endothelial nitric-oxide synthase
      activation].
AB  - This article deals with the influence of shear stress on endothelial NO
      synthesis, and the role of caveolae in shear stress-induced eNOS activation.
      Human umbilical vascular endothelial cells (HUVEC) were cultured and exposed to
      different levels of laminal shear stress and Filipin, the perfused cultures were
      collected, and NO(2-)/NO(3-) was detected using nitrate reduction method. The
      structure of caveolae was observed through transmission electron microscopy
      (TEM). The level of NO(2-)-/NO(3-) was found to increase with the elevation of
      shear stress level (P < 0.01). It was the highest at 1.5 N/m2. After treatment
      with Filipin, the level of NO produced by HUVEC decreased significantly (P <
      0.01), but after recovery and shear without Filipin, the level of NO synthesis
      bounded back (P < 0.01). It was then concluded that shear stress can induce
      endothelial NO synthesis and caveolae plays a key role in shear stress-induced
      eNOS activation.

PMID- 16294745
TI  - [Expression of human papillomavirus 16 E7 DNA in patients with colorectal
      adenocarcinoma].
AB  - The relationship between Human papillomavirus (HPV) 16 infection and the natural
      course of colorectal adenocarcinoma has not been fully defined. In this study,
      the HPV 16 E7 DNA was detected in 82 patients with primary colorectal
      adenocarcinoma to study the relationship between HPV 16 infection and colorectal
      carcinoma. Samples were taken from both the tumors and the adjacent normal mucosa
      in the same patient. Polymerase chain reaction (PCR) was used to amplify the
      HPV16 E7 DNA fragment. The PCR products were gel-purified and sequenced for HPV
      genotyping. DNA sequence analysis indicated that PCR product was 297 bp. It was
      the equivalent of 562-858th pairs in the HPV 16 primitive sequences. Our results
      showed HPV16 E7 DNA expression was significantly higher in colorectal carcinoma
      (42/82) than in adjacent normal mucosa (4/82). The correlation was found between
      HPV16 E7 expression and tumor's location; the positive rate was 18.18% in the
      ascending colon carcinoma group and 64.10% in the rectal carcinoma group. High
      HPV16 E7 expression was also associated with lower Dukes stage (P < 0.01). These
      results indicated that there was correlation between colorectal adenocarcinoma
      and HPV 16 infection. HPV16 infection was relatively higher in the colorectal
      carcinoma and rare in the adjacent normal mucosa. Specimens expressing higher
      levels of HPV 16 E7 DNA were associated with lower Dukes stage and more distal
      location.

PMID- 16294746
TI  - [Proliferation and differentiation of C-kit+ cell in vitro].
AB  - This study sought to isolate and purify C-kit+ cells from rat 2-AAF/PH model and
      to investigate the proliferation and differentiation of C-kit+ cells in vitro. C
      kit positive oval cells were enriched by using magnetic activated cell sorting
      (MACS). The sorted oval cells were cultured in a low density, and then colony
      formation was observed. The capacity of proliferation and differentiation of C
      kit positive cells were examined in vitro by immunocytochemistry and RT-PCR. By
      using C-kit antibody in conjunction with MACS, we developed a rapid oval cell
      isolation protocol. The sorted cells formed colony when cultured in vitro. Cells
      in the colony expressed albumin or cytokeratin 19 (CK19) or coexpressed both, and
      BrdU incorporation test was positive. RT-PCR on colony showed expression of
      albumin and CK19 gene. The results demonstrate that by means of MACS we have
      established a method to isolate oval cells. The sorted hepatic oval cells can
      form colony in vitro which expresses different combinations of phenotypic markers
      and genes from both hepatocytes and cholangiocyte lineage.

PMID- 16294747
TI  - [Synthesis of peptide fragment of melittin and the function of rheumatoid
      arthritis cure].
AB  - To retain the anti-rheumatoid arthritis activity of melittin and to reduce the
      hemolysis and hypersusceptibility caused by melittin, a deletion peptide of
      melittin was synthesized. Its ant-inflammation effect was observed . A hydrophile
      peptide fragment of melittin was synthesized by standard solid-phase method. The
      product was analyzed by HPLC and MS. The relevant hemolysis and
      hypersusceptibility were tested. The rabbits' model of immune arthritis were
      established and treated. The results showed that the hemolysis rate for peptide
      fragment was less than 5%, the hypersusceptibility rate was less than 8%. The
      hydrophile peptide fragment of melittin may retain anti-rheumatoid arthritis
      activity and reduce the melittin-induced hemolysis and hypersusceptibility.

PMID- 16294748
TI  - [Single visual-evoked potential estimation based on sparse decomposition].
AB  - Iterative weighted sparse decomposition is a method to determine the weight
      coefficients of the minimum l1 norm optimization in accord with the two-scale
      relationship of the white noise in the multiresolution wavelet structure and to
      gradually suppress the influence of the strong noises through an iteration
      operation. The single-trial Visual Evoked Potential(VEP) estimation results
      confirmed the effectiveness of the method, and thus supported the viewpoint that
      the results of the single VEP estimation were different.

PMID- 16294749
TI  - [Development of a piezoelectric sensor for detection of low endotoxin
      concentration].
AB  - Endotoxin is an important factor which can lead to endotoxemia and complication.
      Accurate detection of its concentration is very useful for the diagnosis and
      treatment of these diseases. A piezoelectric biosensor for detecting endotoxin
      was developed, which was based on liquid damping effect of quartz crystal
      resonator. The test results showed that the maximal frequency shift of sensor is
      linearly dependent on the logarithm value of concentration of endotoxin (0.1 pg/m
      - 10 ng/ml). The time which d (deltaf)/dt(maax) appeared in frequency shift curve
      was also linearly dependent on the logarithm value of concentration of endotoxin
      (0.01 pg/ml - 10 ng/ml). The detection time was shortened and the minimal limit
      of detection was decreased using the second method. Thus the proposed sensor is
      much simpler, more precise and has more lower limit of detecting detection of
      endotoxin when compared with the conventional methods.

PMID- 16294750
TI  - [Application of support vector machine in the detection of early cancer].
AB  - Support Vector Machine (SVM) is an efficient novel method originated from the
      statistical learning theory. It is powerful in machine learning to solve problems
      with finite samples. Due to the deficiency of cancer cells, character of patient
      and noise in the raw data, it is very difficult to diagnose early cancer
      accurately. In this paper, SVM is employed in detecting early cancer and the
      results are encouraged compared with conventional methods. The accuracy of Non
      linear SVM classifier is especially high in all kinds of classifiers, which
      indicates the potential application of SVM in early cancer detection.

PMID- 16294751
TI  - [A kind of method for time-frequency analysis of electrocardiosignal imitation].
AB  - Electrocardiosignal (ECG) is an important evidence base for the diagnoses of
      cardiovascular diseases as well as for the researches in basic and clinical
      medicine. Because it presents typical non-steady signals, the wave in time can
      not reflect the essential characteristic very well. In this article, by analysis
      in time-frequency domain, we have obtained some typical time-frequency diagrams
      of normal ECG and abnormal ECG, which reflect the comparatively essential
      characteristics of the original signal in some aspects and seem likely to become
      a basis for validating the relevant diagnosis.

PMID- 16294752
TI  - [A theoretical model study of open section effect on the mechanical properties of
      long bone].
AB  - The mechanical model of femur mid-diaphysis with a rectangular open section in
      the exterior cortex was developed and a finite element method was adopted in
      calculating and analysing the changes of torsional stiffness and the stress
      distribution when the dimension of the open section altered. It showed that the
      open section with a length of 1 OD (femur mid-diaphysis diameter) had little
      influence on the femur torsional stiffness or stress distribution. The torsional
      stiffness decreased most dramatically as the length increased from 2 to 4 OD.
      Shear stress peaked at the center of the open section. This conclusion provides
      an important theoretical ground for the operative methods and the dimension
      control of an open section in clinical orthopaedics.

PMID- 16294753
TI  - [A preliminary clinical study on absorbable screws].
AB  - To evaluate the application of self-reinforced ploy-DL-lactide (SR-PDLLA)
      absorbable screws in the treatment of spongy bone and intra-articular fractures,
      the internal fixation with SR-PDLLA absorbable screw was performed on 58 cases,of
      which 25 were medial malleolus fractures, 14 condyle of humerus fractures, 9
      tibial plateau fractures, 7 ulnar olecranon fractures, and 3 lateral malleolus
      fractures. Observations were made on the orthopaedic operation sites and overall
      conditions frequently and radiography was performed for periodic analysis. The
      results showed that SR-PDLLA absorbable screws were particularly effective and
      reliable, they had good biocompatibility in the treatment of spongy bone and
      intra-articular fractures and could be used safely in clinical practice.

PMID- 16294754
TI  - [Research on EMD and its application in biomedical signal processing].
AB  - In this paper a new technique, Empirical Mode Decomposition(EMD), for use in non
      stationary and non-linear data processing, was introduced. Some simulated signal,
      real ECG and RRI signals combined with Hilbert Transform method were analyzed.
      The authors also put emphasis on the differences between EMD and Wavelet
      Transform.

PMID- 16294755
TI  - [Establishment of a system for measuring blood flow velocity of rat microvessel
      using dark background fluorescent image analysis method].
AB  - Autologous red blood cells (RBC) labeled with fluorescence were immitted into
      microvessel of SD rat and observed under microscope. The movement of each
      individual labeled RBC was recorded by microscope video camera system. The
      recorded videotape is replayed to sample dark background fluorescent images
      through frame grabber. Sampled frame images were separated into odd and even
      field sequence images. Then these sequence images were analyzed to get the flow
      rate. The error between the actual flow velocity value and the flow velocity
      value of fluorescent globules in the chamber measured under the same system was
      below 7%. The upper limit was 9.6 mm/s. There are no obvious differences (P >
      0.05). This system has been applied in the research of rat microcirculatory
      disturbance, and the temporal flow rate change in microvessel was obtained.

PMID- 16294756
TI  - [Harmfulness of nickel in medical metal materials].
AB  - Medical metal materials is widely used in medical field due to its excellent
      properties; the nickel ions leaching from stainless steel because of corrosion
      have the harmfulness of malformation and cancerization besides allergenicity in
      human body. Potential harmfulness of nickel in medical metal materials and new
      trend on research and development are reviewed in this paper, and both the
      advantage and the long term potential development of nickel-free medical
      stainless steels are also described on the basis of our own research work.

PMID- 16294757
TI  - [Progress in vitreous cryopreservation of living bioproducts].
AB  - In this brief review, some key issues related to vitreous cryopreservation of
      living tissues (natural or engineered), including cells, embryos, tissues,
      organs, and engineered tissues, are outlined. The principle of vitreous
      cryopreservation for the biological activity and functionality is demonstrated.
      The procedures of cooling/ rewarming, composition and function of optimal
      cryoprotectants, and their effects on bioproducts are described. Vitrification
      could, therefore, prove to be a useful and effective method of bioproduct
      cryopreservation for a long period of time, particularly for organized tissues
      and organs. However, the toxicity of the cryoprotective agents and the
      devitrification occurring during the rewarming process need additional
      investigations. Several key areas of research on vitrification are also
      addressed.

PMID- 16294758
TI  - [Perforin and granzyme--the perfect material of biologic missile].
AB  - Perforin and granzyme are important effector molecules in cytolytic cells. They
      can induce apoptosis of tumor cells and infection cells. The research of biologic
      missile is noticed with the progress in therapy targeting to the disease. It is
      supposed that perforin and granzyme play an important role in biological missiles
      because of their biologic function and structure. A review on several aspects of
      these effector molecules is presented.

PMID- 16294759
TI  - [Advances in medical image registration based on mutual information].
AB  - The matching algorithm based on mutual information, which has the advantages of
      high speed, good automation and superion accuracy, is widely used in medical
      image registration. In this paper are presented the basic conception of mutual
      information, the transform model, the insert value algorithm, the optimization
      algorithm and the strategy in computing mutual information. Furthermore, we
      introduce some efficient methods for solving the problems in registration
      technique based on mutual information, and look forward to the future research
      work.

PMID- 16294760
TI  - [Shape-memory polymers for biomedical engineering applications].
AB  - The latest progress in shape-memory polymer for biomedical engineering
      applications was summarized in this paper. The mechanism responsible for shape
      memory effect was analyzed in reference to the polymer structure. Also introduced
      and reviewed were the characteristics of some shape-memory polymers (polyurethane
      polycaprolactone and polylactide) and their applications in medical engineering.

PMID- 16294761
TI  - Partnership works.

PMID- 16294762
TI  - Feeling the benefit.

PMID- 16294763
TI  - Respect inspections, minister.

PMID- 16294764
TI  - Memories of war.

PMID- 16294765
TI  - Ageism.

PMID- 16294766
TI  - Developing person-centred dementia care in acute settings: findings from a study
      tour in Australia.

PMID- 16294767
TI  - Dysphagia in a general practice population.

PMID- 16294768
TI  - Understanding bowel problems in older people: part 1.
AB  - Bowel problems can be devastating for patients and those who care for them.
      Accurate assessment is essential to determine the cause of symptoms and to decide
      treatment and management strategies. Treatment and management can be complex but
      with care and patience improvement or cure is possible. Part 1 of this two-part
      article offers an overview of bowel problems in older people and an introduction
      to assessment.

PMID- 16294769
TI  - Foot care for non-diabetic older people.

PMID- 16294770
TI  - Dementia care at the centre.

PMID- 16294771
TI  - Stand up and be counted.

PMID- 16294772
TI  - Modeling and output tracking of transverse flux permanent magnet machines using
      high gain observer and RBF neural network.
AB  - This paper deals with modeling and adaptive output tracking of a transverse flux
      permanent magnet machine as a nonlinear system with unknown nonlinearities by
      utilizing high gain observer and radial basis function networks. The proposed
      model is developed based on computing the permeance between rotor and stator
      using quasiflux tubes. Based on this model, the techniques of feedback
      linearization and Hinfinity control are used to design an adaptive control law
      for compensating the unknown nonlinear parts, such as the effect of cogging
      torque, as a disturbance is decreased onto the rotor angle and angular velocity
      tracking performances. Finally, the capability of the proposed method in tracking
      both the angle and the angular velocity is shown in the simulation results.

PMID- 16294774
TI  - Development of characteristic equations and robust stability analysis for MIMO
      move suppressed and shifted DMC.
AB  - Discrete-time controller and closed-loop transfer functions were developed for
      move suppressed lambda and the recently formulated m-shifted multiple-input
      multiple-output (MIMO) dynamic matrix control (DMC). Using these transfer
      functions, robust analyses were conducted for MIMO plants by varying
      corresponding delay and gain ratios of the system. In all instances, robust plots
      indicate that the shifted DMC is less sensitive and hence more robust to
      variations in the plant parameters than move suppressed DMC. It was shown that
      the design of these MIMO DMC controllers depends on the plant closed-loop
      performance and overall stability, since the selection of lambda and m directly
      influences the plant robustness and closed-loop dynamics.

PMID- 16294773
TI  - Control loop noise rejection using fuzzy logic.
AB  - This paper describes an application of fuzzy logic to noise rejection in a
      control loop. This new use of fuzzy logic solves the problem of sluggish control
      loop response when using a set-point range to stop constant valve chattering due
      to noise in the output signal being sent to a control valve. Multiple related
      variables and a general understanding of their inter-relationship must be
      available for this method to be successfully applied. An overview of the specific
      fuzzy logic method used for this application is presented along with guidelines
      for the practical application. In addition, this paper includes results from the
      successful implementation of fuzzy logic to a control loop on a pilot plant
      distillation column.

PMID- 16294775
TI  - A novel sliding-mode control of induction motor using space vector modulation
      technique.
AB  - This paper presents a novel sliding-mode control method for torque control of
      induction motors. The control principle is based on sliding-mode control combined
      with space vector modulation technique. The sliding-mode control contributes to
      the robustness of induction motor drives, and the space vector modulation
      improves the torque, flux, and current steady-state performance by reducing the
      ripple. The Lyapunov direct method is used to ensure the reaching and sustaining
      of sliding mode and stability of the control system. The performance of the
      proposed system is compared with those of conventional sliding-mode controller
      and classical PI controller. Finally, computer simulation results show that the
      proposed control scheme provides robust dynamic characteristics with low torque
      ripple.

PMID- 16294776
TI  - Auto-tuning of PID controller parameters with supervised receding horizon
      optimization.
AB  - In this paper, a novel two-layer online auto-tuning algorithm is presented for a
      nonlinear time-varying system. The lower layer consists of a conventional
      proportional-integral-derivative (PID) controller and a plant process, while the
      upper layer is composed of identification and tuning modules. The purpose of the
      upper layer is to find a set of optimal PID parameters for the lower layer via an
      online receding horizon optimization approach, which result in a time-varying PID
      controller. Through mathematical analysis, the proposed system performance is
      equivalent to that of a standard generalized predictive control. Simulation and
      experiment demonstrate that the new method has a better control system
      performance compared with conventional PID controllers.

PMID- 16294777
TI  - Failure-tolerant performance stabilization of the generic large-scale system by
      decentralized linear output feedback.
AB  - Most of the existing results on the decentralized stabilization of large-scale
      systems consider systems in the input-output-decentralized form, i.e., systems
      whose input and output matrices are block diagonal. The controller synthesis for
      such systems is less involved than that for input-output-centralized ones. In
      this paper, a transformation is proposed for the input-output decentralization of
      the generic large-scale system. Using the transformed system, a sufficient
      condition for failure-tolerant performance stabilization of the original large
      scale system in a desirable performance region under decentralized linear output
      feedback is established. The problem is then reformulated as a constrained
      nonlinear optimization problem. The proposed methodology results in the optimal
      reconciliation of failure-tolerant performance stabilization of the overall
      system, and reliability and low actuator gains of the isolated subsystems. The
      effectiveness of the proposed approach is demonstrated by an example.

PMID- 16294778
TI  - Additive fault detection in nonlinear dynamic systems with saturation.
AB  - This paper describes the effects of input saturation on the performance of a
      model-based fault detection method based on the input-output parity equation
      approach. For this purpose, the level control of a chemical reactor has been
      chosen as the control process to be analyzed, where the saturation of the dynamic
      process is due to the inflow control valve, and only additive faults have been
      considered. This study has been carried out in two ways: first by simulation
      techniques and second on a real industrial system. In the simulated case, the
      decrease in the fault detectability due to the saturation effects is shown, and
      some ways of achieving higher fault detectability are explored. The results
      obtained in the industrial case complement those obtained in the simulated case,
      and also reveal the existence of a relation between the control strategy used in
      the process and additive fault detectability, in the sense that increases in
      fault detectability are obtained due to the use of faster control strategies.

PMID- 16294779
TI  - Modeling a multivariable reactor and on-line model predictive control.
AB  - A nonlinear first principle model is developed for a laboratory-scaled
      multivariable chemical reactor rig in this paper and the on-line model predictive
      control (MPC) is implemented to the rig. The reactor has three variables
      temperature, pH, and dissolved oxygen with nonlinear dynamics-and is therefore
      used as a pilot system for the biochemical industry. A nonlinear discrete-time
      model is derived for each of the three output variables and their model
      parameters are estimated from the real data using an adaptive optimization
      method. The developed model is used in a nonlinear MPC scheme. An accurate
      multistep-ahead prediction is obtained for MPC, where the extended Kalman filter
      is used to estimate system unknown states. The on-line control is implemented and
      a satisfactory tracking performance is achieved. The MPC is compared with three
      decentralized PID controllers and the advantage of the nonlinear MPC over the PID
      is clearly shown.

PMID- 16294780
TI  - [Advances in cryotherapy].

PMID- 16294781
TI  - [Circumcision in religious art].
AB  - OBJECTIVES: The objective of this study is to perform a historical journey
      through the topic of circumcision from the Italian Renaissance to the Spanish
      Baroque. METHODS: We evaluated the paintings about circumcision between both
      periods, including their most representative works. RESULTS AND CONCLUSIONS:
      Circumcision is a frequent topic in the religious painting in both periods.

PMID- 16294782
TI  - [Orthotopic bladder substitution in the treatment of interstitial cystitis].
AB  - OBJECTIVES: To point out the efficacy of supra trigonal cystectomy with
      orthotopic substitution iliocystoplasty in the treatment of advanced interstitial
      cystitis (IC). METHODS: We study the results obtained in four women suffering IC
      nonrespondent to conservative treatment who underwent the procedure. All patients
      comply with classic diagnostic criteria of IC, presenting long-lasting symptoms,
      between 4 and 8 years (mean 5.6), and voiding frequency of near one-hour day and
      night. RESULTS: Mean postoperative follow-up was 32 months (18 to 56); post
      operative evaluation included clinical evaluation, ultrasound, urodynamic
      studies, and radiological tests. Suprapubic pain disappeared in all cases, as
      well as pre-op lower urinary tract symptoms, with good control of urinary
      frequency day and night being evident in the immediate postoperative period. All
      patients referred high satisfaction with the outcome. CONCLUSIONS: When
      conservative treatment fails, supratrigonal cystectomy with orthotopic neobladder
      substitution is a valid therapeutic option in IC patients who comply with classic
      diagnostic criteria.

PMID- 16294783
TI  - [Results of a series of transrectal ultrasound guided biopsy of the prostate in
      6000 patients. Part I: pathology, digital rectal examination, transrectal
      ultrasound, and PSA].
AB  - OBJECTIVES: To analyze the results of transrectal ultrasound (TRUS) guided biopsy
      of the prostate in 6000 patients, and their relation to common-use clinical
      parameters. METHODS: We collected PSA, digital rectal examination, TRUS
      characteristics, and pathology report in a data- base including 6000 patients who
      underwent sextant TRUS biopsy from 1994 to December 2002. 861 of them underwent
      more than one biopsy, accounting for a total of 7127 biopsies. Sextant biopsy
      with samples from the most lateral portions of the prostate was the standard
      procedure so that they included peripheral zone only. We analyze pathological
      results and their relation with clinical variables. RESULTS: Total percentage of
      cancer in biopsy samples was 42.6%, with 39.1% in the first biopsy. Overall,
      repeated biopsies resulted in a 3.5% diagnostic yield increase. PIN or focal
      glandular atypia were detected in 2.0% and 2.1% of the cases respectively. The
      percentage of patients with Gleason score =<6 increased from 41.8% in the first
      biopsy to 70% in the third. Similarly, single core involvement increased from
      21.% to 65%. Digital rectal examination and presence of hypoechogenic nodules
      specificity were 82.6 and 78.2% respectively. The incidence of prostate cancer
      with PSA between 4 and 10 ng/ml was 29.6%, 16.7% in those with PSA lower than 4
      ng/ml. CONCLUSIONS: TRUS biopsy of the lateral prostatic areas offers a good
      diagnostic yield in comparison with most series of extensive biopsies. The
      sensitivity of TRUS has decreased but it maintains a high specificity which
      should not be forgotten when planning the TRUS strategy

PMID- 16294784
TI  - [Results of a series of transrectal ultrasound guided biopsy of the prostate in
      6000 patients. Part II: PSA derived parameters].
AB  - OBJECTIVES: We review the results of 6000 patients with the clinical suspect of
      prostate cancer who underwent one or more prostate, biopsies, analyzing the role
      of PSA derived parameters in the probability of having prostate cancer in the
      TRUS biopsy. METHODS: We selected 6000 patients who under- went TRUS biopsy
      between 1994 and 2002. 861 of them underwent more than one is biopsy, adding up
      to a total of 7127 biopsies. For the study of PSA derived indexes we established
      ranges based on the 10th percentile for the first biopsy for all patients and
      also for those with PSA between 4 and 10 ng/ml. Several predictive models were
      determined by logistic regression of the variables related with presence/no
      presence of cancer. RESULTS: For first biopsies the ranges of PSAD established
      showed a diagnostic effectiveness below 8% with PSA densities lower than 0.11
      ng/ml/cc. The free/total PSA ratio is less discriminant in the ranges obtained
      with a 13.7% incidence of prostate cancer for values above 0.24. In the case of
      second biopsies the group of patients with PSAD below 0.12 had only a 5.3%
      incidence, and only one patient with F/T PSA ratio higher than 0.24 had a
      prostate cancer (2.9%). All studied parameters but F/T PSA ratio showed
      statistical significance in the multivariant analysis. CONCLUSIONS: Although the
      establishment of a cut point for PSAD diminishes sensitivity, prostate biopsy
      habits should be modified assuming the loss of tumors in patients with low PSAD
      and increasing the number of biopsies in patients with total PSA values below 4
      ng/ml with higher densities.

PMID- 16294785
TI  - [Clinical-pathological study of incidental renal cell carcinoma].
AB  - OBJECTIVES: To determine the percentage of renal cell carcinomas incidentally
      diagnosed (IRCC) and to compare their clinical and pathological characteristics
      with symptomatic or non-incidentally diagnosed tumors (SRCC). METHODS: We
      retrospectively study 189 patients who were diagnosed of renal carcinoma between
      1990 and 1999. 166 underwent surgery (149 radical nephrectomy; 17 nephron-sparing
      surgery). We determine the percentage of IRCC detected by radiological tests and
      compare them with the SRCC diagnosed after presenting with some of the classic
      symptoms or metastasis, with special focus on tumor size, pathology stage, tumor
      recurrence, progression and evolution. RESULTS: 87 SRCC (46%); 102 SRCC (54%).
      There are not differences in terms of age, gender, side, and postoperative
      hospital stay. Tumor size was higher in the SRCC (mean 8.5 cm) than in the IRCC
      (6.3 cm). SRCC tumor stage was: pT1 27.3%, pT2 27.3%, pT3a 23.8%, pT3b 16.6%,
      pT3c 2.3%, and pT4 2.3%; IRCC stage was: pT1 51.3%, pT2 25.6%, pT3a 10.9%, pT3b
      10.9%, pT3c 1.2%, and no pT4. The percentage of patients with lymph node
      involvement was higher (p = 0.02) in the SRCC (15%) than in the IRCC (4.8%). The
      percentage of patients with metastasis at the time of diagnosis was higher in the
      SRCC group (26%) than in the IRCC (9.2%). Recurrences were more frequent in the
      SRCC Group (8.3%) than in the IRCC (1.2%) (p = 0.07). Tumor progression was more
      frequent in the SRCC group (34%) than in the IRCC (7.3%) (p<0.01). 76% of the
      patients undergoing nephron sparing surgery were IRCC. CONCLUSIONS: Currently,
      there is a high percentage of IRCC (46% in our series from 1990-99). Renal tumors
      presenting as IRCC have better prognosis, since they have significantly smaller
      size, lower stage, less advanced disease, less recurrences, and less progression
      than SRCC.

PMID- 16294786
TI  - [Urodynamics of the bladder diverticulum in the adult male].
AB  - OBJECTIVES: To evaluate the clinical and urodynamic characteristics of a series
      of adult males with BPH and bladder diverticula, and to analyze the changes in
      urodynamics in patients undergoing lower urinary tract surgery to relieve
      obstruction, with or without associated diverticulectomy. METHODS: We studied 91
      patients in two groups: Group 1- BPH: 67 cases (73.6%) and Group 2-BPH +
      diverticulum: 24 cases (25%). Mean age was 65.04 years. All patients underwent
      urological physical examination and complete urodynamic study including
      cystogram. In addition, we studied 19 patients with BPH and bladder diverticula
      (mean age 64.58 years) who underwent either endoscopic surgery (1 I cases; 57.9%)
      or endoscopic surgery plus diverticulectomy (8 cases, 42. 1%). Complete clinical
      study and urodynamics (including cystogram) were performed preoperative and three
      months after surgery. Statistical significance was established at 0.05. RESULTS:
      Comparative study between group 1 (BPH) and group 2 (BPH with diverticulum):
      there were significant differences in clinical data: acute urinary retention
      (6.1% vs. 25%;p<0.01), and urinary tract infection (3.1% vs. 21.7%;p=0,004). All
      evaluated cases had single diverticula (8 cases). Urodynamic studies showed: 1)
      Post-void residual after free flowmetry: 45.9 ml vs. 221.4 ml, p = 0.008. 2)
      Bladder capacity on cystometrogram: 211.2 ml vs. 350.8 ml, p = 0.024. 3) Voiding
      pressure/flow study: a) Voiding with abdominal press 23.9% vs. 50%, p = 0.02. b)
      URA 36.5 cm H2O vs. 48.5 cm H2O, p= 0.04, c) post void residual 70.7ml vs. 210.3
      ml, p= 0.004. d) Bladder contractility measurements (Wmax- isometric
      contractility- and W80, W20- isotonic contractility) did not show significant
      differences between groups. Bladder contractility duration was significantly
      decreased in group 2. In the analysis of patients undergoing surgery to relieve
      obstruction (Group A- Surgery without diverticulectomy; Group B Surgery with
      diverticulectomy) there were not differences between groups in clinical data.
      Urethral resistance parameters (URA) decreased in both groups. Group A: from 43
      cm H20 to 26.3 cm H2O. Group B: from 60.6 cm H2O to 48 cm H2O. This decrease was
      similar after either TURP or myocapsulotomy. Post void residual diminished in
      both groups. There were no statistical differences between groups in Wmax, W 80
      20, or volume, number and site of the diverticula. On the contrary, bladder
      contractility duration diminished after diverticulectomy. CONCLUSIONS: Bladder
      diverticula appear in the cases with highest ureteral resistance values (lower
      urinary tract obstruction). Standard bladder contractility parameters were not
      diminished. Duration of detrusor contraction was the only contractility parameter
      significantly affected in cases of bladder diverticula and presented a
      significant association with the use of abdominal press while voiding.
      Diverticulectomy showed an improvement of bladder contractility with longer
      detrusor contraction duration, which supports its use in cases of BPH-associated
      diverticula. Both TURP and transurethral incision of the prostate diminished
      urethral resistance in a similar way, so that they may be considered alternative
      options. Our data should be confirmed with a bigger sample size.

PMID- 16294787
TI  - [Botulinum toxin injection for neurogenic and no neurogenic bladder dysfunction].
AB  - OBJECTIVES: Botulinum toxin A (BT A) has gained popularity among urologists in
      the treatment of detrusor muscle dysfunctions. The aim of this article is to
      review our experience with this therapy METHODS: From 2001 we used BT A in 28
      patients. It was injected in the bladder wall under cystoscopical vision. We
      analyze the indication of treatment, clinical data and urodynamics before and
      after treatment. RESULTS: We treated 28 patients. 71 percent had neurogenic
      hyperreflexic bladder, 18% idiopathic unstable bladder and 11% other diseases. No
      direct complications were observed. Neurogenic hyperreflexic bladder (n = 20):
      Mean preoperative bladder capacity was 220 cc, improving to 430 cc after
      treatment. Non inhibited contractions disappeared. All patients except one with
      multiple sclerosis, who had spontaneous voiding, required self catheterization
      after injection. Average time interval between injections was 8.6 months.
      Idiopathic unstable bladder (n = 5): a lower dose was used, with an average of
      100 U. Non inhibited contractions disappeared and all patients were able to
      maintain spontaneous voiding with post void residuals under 50 ml. No patients
      required self catheterization. Bladder capacity improved from 128 ml to 370 ml.
      Average number of voidings per day diminished from 16 to 7 times. Other diseases
      (n = 3): results were poor in these patients. There were no changes in either
      bladder function studies or average voiding frequency (15 times per day). These
      patients required surgery for bladder augmentation in 2 cases and continent
      diversion in 1 case. CONCLUSIONS: BT A has a role in the treatment of neurogenic
      hyperreflexic bladder diminishing incontinence and improving bladder capacity. In
      cases of idiopathic unstable bladder without anatomical changes its results are
      promising, but a limited number of patients does not allow a definitive
      conclusion. In other bladder diseases with anatomical changes results are poor
      and its use should not be routinely recommended.

PMID- 16294788
TI  - [6-year experience with extra peritoneal lumbar laparoscopic surgery:
      indications, complications, and results in a reference Southamerican center].
AB  - OBJECTIVES: To report the experience in lumbar extraperitoneal laparoscopy
      surgery obtained while perfectioning the technique over a six-year period.
      METHODS: We perform a prospective study with 168 cases of extra peritoneal
      laparoscopic surgery for the treatment of various kidney-ureter and adrenal
      diseases between 1999 and 2004. Operations were classified by organ and
      complexity (ablative or reconstructive). We describe the number of cases,
      surgical time, mayor and minor complications, number of open conversions,
      hospital stay, time to return to daily-life activities, advantages and
      disadvantages, as well as comparative analysis with data from bibliography.
      RESULTS: Extraperitoneal access was employed in 168 laparoscopic operations: 44
      renal biopsies, 8 renal cyst marsupializations, 49 nephrectomies (22 benign
      diseases/27 neoplasias). 15 nephroureterectomies. 22 adrenalectomies. 15
      pyelolithotomies/ureterolithotomies, 1 neprhropexy, 2 partial nephrectomies. 11
      pyeloplasties and 1 correction of retrocaval ureter. Operative time decreased
      significant only after the initial adaptation, with an average of 118 minutes in
      138 ablative operations and 163 minutes in 30 reconstructive procedures. There
      was only one conversion in the second case of the series. The incidence of mayor
      and minor complications was 5.07% and 4.34% respectively for ablative surgery and
      3.33% and 6.66% for reconstructive surgery. Average hospital stay varied from 1-4
      days. Return to daily life activities took an average of 7 to 30 days in relation
      with procedure complexity. CONCLUSIONS: Lumbar extra peritoneal laparoscopic
      access is an excellent option of minimally invasive approach to ablative surgery,
      offering the advantages of avoidance of the peritoneal cavity and low
      complication index. Reconstructive surgery is feasible but technically more
      challenging, depending of the ability and adaptation of the surgeon to a smaller
      surgical workspace.

PMID- 16294789
TI  - [Secondary bladder amylodosis with severe recurrent hematuria: transurethral
      Mikuliz procedure as hemostatic option].
AB  - OBJECTIVES: Primary localized amyloidosis of the urinary bladder generally has a
      benign course. On the contrary, secondary amyloidosis, a consequence of systemic
      amyloidosis, may have massive bleeding and produce complications such as bladder
      rupture or lifethreatening hemodynamic problems requiring desperate hemostatic
      procedures such as hypogastric artery embolization or ligature, or cystectomy. We
      report one case in which hemostasis was achieved by a Mickulicz transurethral
      bladder tamponage. METHODS: 58 year old female with very aggressive rheumatoid
      arthritis and secondary renal amyloidosis under chronic hemodialysis presenting
      with severe hematuria after hip replacement. An inflamed bladder was found, the
      biopsy of which showed edema in all layers with blood vessel walls enlarged by
      amiloyd deposits. After several unsuccessful transurethral hemostatic procedures,
      intravesical formalin irrigation was carried out together with a Mikulicz type
      gauze packaging after urethral dilation. The gauze was withdrawn three days later
      without bleeding recurrence; however she presented subsequent neurological
      impairment and finally died 14 days after the last urological procedure.
      CONCLUSIONS: Transurethral packaging of the urinary bladder in a woman with
      massive hematuria is a hemostatic option that we recommend to be used before
      other more dramatic or invasive options are chosen.

PMID- 16294790
TI  - [Giant bladder hernia associated with bilateral incipient obstructive uropathy].
AB  - OBJECTIVES: To report one case of giant inguinal scrotal bladder hernia
      associated with incipient bilateral obstructive uropathy. METHODS: We report the
      case of a 54-year-old male patient presenting with two-time interrupted voiding,
      with the need of scrotal compression to complete voiding. Physical examination
      showed a great left inguinal scrotal hernia with significant post void residual
      before compression. Serum creatinine was 1.7 mg/dl. Voiding cystourethrogram and
      intravenous urography confirmed the diagnosis of bladder hemia with mild
      hydronephrosis. Inguinal hernioplasty with bladder hernia reduction was
      indicated. RESULTS: Morphologically and functionally satisfactory. Clinical and
      analytical normalization. CONCLUSIONS: We emphasize the rarity of bilateral
      supravesical obstructive uropathy secondary to bladder hernia. We concur with
      other authors in the validity of conservative reconstructive surgery in cases
      such as the one reported.

PMID- 16294791
TI  - [Malignant melanoma of the penis. Report on one case].
AB  - OBJECTIVES: Due to the fact that melanoma of the penis is rare, we perform a
      bibliographic review about the subject and analyze the diagnostic criteria,
      clinical stages and therapeutic options. METHODS: We report one case that was
      diagnosed and treated in our department. RESULTS: 85-year-old male who presented
      with hematuria and a red brownish irregular elevated lesion in the glans penis.
      Partial penectomy was performed. CONCLUSIONS: Melanoma of the penis is a rare
      tumoral entity. It accounts for about 1% of all penile malignant pathologies. It
      has bad prognosis due to fast metastosic dissemination (regional lymph nodes and
      other organs) and delayed diagnosis. First choice treatment is partial penectomy
      with or without bilateral inguinal lymphadenectomy (depending upon degree of
      tumor invasiveness). In cases with metastasis treatment is palliative with
      chemotherapy and immunotherapy

PMID- 16294793
TI  - [Adenocarcinoma of the female urethra: report of two cases and bibliography
      review].
AB  - OBJECTIVES: Primary adenocarcinoma of the female urethra is a rare malignancy. We
      report two cases and a review of the latest articles focused on classification
      and treatment of this kind of neoplasm. METHODS: We present two females diagnosed
      of urethral adenocarcinoma, describing clinic and pathological features,
      diagnosis and treatment. CONCLUSIONS: Female urethral adenocarcinoma is an
      uncommon neoplasm with a heterogeneous histogenesis. The distal urethral
      carcinoma is more amenable to treatment, and the prognosis is better than that of
      proximal or entire urethral carcinoma, which is often associated with extensive
      local invasion and metastasis.

PMID- 16294792
TI  - [Brucella orchyoepididymitis: case report].
AB  - OBJECTIVES: To report one case of unilateral acute orchiepididymitis due to
      Brucella and to review its diagnosis and treatment in the related literature.
      METHOD: We report the case of a 37-year-old-male with undulant fever, scrotal
      pain and swelling and osteoarticular involvement. Diagnosis was obtained by
      anamnesis, blood cultures and specific serologic tests for Brucella. RESULTS:
      Antibiotic therapy with orally administered Doxycycline (6 weeks) and im
      administered Streptomycin (3 weeks). Complete clinical resolution was achieved.
      CONCLUSIONS: We must perform an exhaustive anamnesis looking for a history of
      contact with animals or ingestion of contaminated dairy products in endemic areas
      of Brucella when facing the case of orchiepididymitis resistant to usual
      antibiotic therapy. The diagnosis is based on Brucella spp. isolation in blood
      cultures and on positive serologic tests (Rose Bengal test, standard
      seroagglutination test, anti-Brucella Coombs test, Brucellacapt test).
      Doxycycline with Streptomycin or Rifampin for 6 weeks seems to be the most
      adequate combinations of antibiotics. Surgical treatment only in exceptional
      cases.

PMID- 16294794
TI  - [Pancreatic fistula after left nephrectomy].
AB  - OBJECTIVES: To report our experience with pancreatic fistula after left
      nephrectomy to point out this unfrequent complication. METHODS: We perform a
      chart review of 3 cases of pancreatic fistula after left nephrectomy experienced
      in our institution between 1983-2004. RESULTS: All patients were males, with an
      average age of 51 years. Indications for nephrectomy were renal cell carcinoma,
      renal abscess and pyonephrosis. Classic Israel incision was the surgical approach
      in all three cases, with accidental opening of the peritoneum. Wound inflammatory
      signs appeared on third postoperative day, drainage of pancreatic juice on
      postoperative day 4. Treatment consisted on NPO 7 days, and intravenous
      hydration, atropin and wide spectrum antibiotics. Mean duration of pancreatic
      juice drainage was 8 days. CONCLUSIONS: Pancreatic tail injury is a possible
      complication of left nephrectomy due to the close anatomical vicinity of both
      organs, that may be altered by tumoral or inflammatory disease of the kidney. If
      not recognized, it may lead to a pancreatic fistula, the diagnosis and treatment
      of which should be known by the urologist.

PMID- 16294795
TI  - [Giant retroperitoneal cystic lymphangioma in adults].
AB  - OBJECTIVES: To report one case of retroperitoneal cystic lymphangioma in an adult
      patient. METHODS: We describe the case of a 70 year-old female patient who
      complained of periumbilical pain and progressive increases of abdominal perimeter
      over a few months. Physical examination showed a great abdominal mass; CT scan
      confirmed its cystic nature. The indication of surgery was established. RESULTS:
      complete lesion excision. Pathology report showed the definitive diagnosis of
      cystic lymphangioma. No evidence of disease after one year. CONCLUSIONS: We
      emphasize that it is an unfrequent type of retroperitoneal neoplasias in the
      adult age. We concur with other authors in the importance of complete excision.

PMID- 16294796
TI  - [Multiple lithiasis radically or totally cured with laser technology. "Use of
      holmium in the treatment of urinary lithiasis"].

PMID- 16294797
TI  - Embolization of a bleeding aneurysm in a patient with spontaneous perirenal
      haematoma due to Polyarteritis nodosa.
AB  - OBJECTIVE: To report a rare case of a Spontaneous perirenal haematoma due to
      Polyarteritis nodosa treated with a selective embolizacion of the bleeding
      aneurysm. Polyarteritis nodosa (PAN) is one of a spectrum of diseases thet
      belongs to the pathologic category of necrotizing vasculitis. Spontaneous
      perirenal haematoma (SPH) is an unusual complication of PAN. METHODS: We are
      introducing a patient with SPH due to PAN. RESULTS: The patient was treated with
      embolization of a left renal bleeding aneurysm of the upper interlobar artery.
      Pan is the most frequent vascular disease associated with spontaneous renal
      hematoma. Therefore the diagnosis may be difficult to determine. CONCLUSIONS: A
      selective embolization of the bleeding aneurysm is a therapeutical maneuver to be
      considered.

PMID- 16294798
TI  - Disaster preparedness: are you ready?

PMID- 16294799
TI  - Summary of the GAO report: Medicare--more specific criteria needed to classify
      inpatient rehabilitation facilities.

PMID- 16294800
TI  - Major depression in rehabilitation care.

PMID- 16294801
TI  - Implementation of efficacy enhancement nursing interventions with cardiac elders.
AB  - Intervention strategies based on social cognitive theory and encompassing the bio
      psycho-behavioral domains are proposed to enhance self-efficacy in men and women
      65 years and older recovering from myocardial infarction and coronary artery
      bypass grafting. This paper describes a study in which the theory-based
      development of efficacy enhancement (EE) nursing interventions and their
      implementation and utilization with interventions from the Nursing Interventions
      Classification (NIC) were used with cardiac elders in the treatment group of the
      community-based randomized clinical, trial, "Improving Health Outcomes in
      Unpartnered Cardiac Elders." Advanced practice nurses (APNs) provided the nursing
      intervention to 110 participants (mean age = 76.2, SD = 6.0) for the first 12
      weeks after discharge to home. After an initial introductory meeting in the acute
      care setting, participant contacts by the APNs were made at a home visit and
      telephone calls at 2, 6, and 10 weeks. Results describe the number of
      participants receiving interventions at all contacts over 12 weeks, at specified
      contact points, and the intensity (nurse time) of the interventions. Verbal
      encouragement and mastery were EE interventions used with the greatest number of
      participants. Exercise promotion, energy management and active listening were NIC
      interventions used with the most participants. Variations in the use of
      interventions over 12 weeks and their intensities, suggest patterns of recovery
      in the elders. During rehabilitation EE interventions can be successfully
      implemented with men and women 65 years and older and individualized to the
      recovery trajectory. Nurses can integrate specific EE interventions with more
      general interventions from the bio-psycho-behavioral domains to enhance the
      recovery process for cardiac elders.

PMID- 16294802
TI  - Predictors of disorientation among brain injury and stroke patients during
      rehabilitation.
AB  - Predictors of temporal disorientation among brain injury and stroke patients
      undergoing rehabilitation were explored in this descriptive study. Cognitive
      orientation is a construct of consciousness, and the Parallel Distributed
      Processing model provided a framework for conceptualizing consciousness in this
      study. Data were collected by a retrospective chart review of a convenience
      sample of stroke and brain injury patients admitted to an acute rehabilitation
      hospital over 4 months. The dependent variable in the study was the Temporal
      Orientation Test used as a daily measure in the study hospital. A total of 167
      patients were admitted during the time frame, and of those, 114 patients met the
      study criteria and were included in the data analysis. The independent variables
      were defined as age, gender, years of education, number of comorbidities, patient
      diagnosis, orientation status on admission, and use of narcotic/sedative
      medications. A logistical regression was performed using SPSS Release 11.01. Only
      one of the six variables--orientation status on admission-reliably predicted the
      onset of disorientation during the rehabilitation stay with an odds ratio of
      0.217, p < .001. This indicates that the risk of becoming disoriented after a
      period of orientation during the rehabilitation stay increased by 78% among
      patients who are disoriented on admission to rehabilitation, compared with those
      who are oriented on admission. These findings confirm that temporal orientation
      is unstable during the period of rehabilitation following a brain injury or
      stroke.

PMID- 16294803
TI  - Taste preference and rating of commercial and natural thickeners.
AB  - Dysphagia can negatively affect quality of life, nutritional status, and
      pulmonary status of individuals. The most common intervention for dysphagia is
      the use of thickening agents for liquids. This group study (n = 43) investigated
      the taste preference, taste ratings, and ranking for nectar-thick hot and cold
      beverages using three types of thickeners: SimplyThick, Thick-It, and
      noncommercially prepared natural thickeners. Results demonstrated a significant
      difference between the taste ratings of two commercial thickeners and between one
      commercial and the natural thickener for the ranking of taste with hot beverages.
      Every participant rated at least one of the thickener beverages as having an
      acceptable taste for the hot chocolate and fruit juice beverages. Exploring
      individual preferences is critical to selecting a beverage that increases
      compliance to clinical recommendations.

PMID- 16294805
TI  - Occurrence and diversity of mosquitocidal strains of Bacillus thuringiensis.
AB  - Ever since the discovery of the first Bacillus thuringiensis strain capable of
      killing mosquito larvae, namely, B. thuringiensis var israelensis, there are
      several reports from different parts of the world about the occurrence of
      mosquitocidal strains belonging to different subspecies/serotypes numbering
      thirty-six. The main sources of these wild type strains are soils/sediments,
      plants, animal feces, sick/moribund insects and waters. The toxicity of the
      strains within a subspecies/serotype varied widely. Some of the strains exhibited
      toxicity to mosquitoes as well as lepidopterans and dipterans (including
      mosquitoes) as well as plant parasitic nematodes.

PMID- 16294804
TI  - There are a few things you did not ask about my pain: writing on the margins of a
      survey questionnaire.
AB  - This qualitative study is a secondary analysis of comments written on survey
      questionnaires about pain mailed to community-dwelling persons with spinal cord
      injury (SCI) or amputation. Narrative comments were added by 54.1% of 797
      respondents. The purpose of this study was to determine the characteristics of
      those who wrote comments and to understand what was being communicated in their
      comments. A qualitative content analysis was used to identify the major themes,
      subthemes, and thematic categories in the unsolicited comments. The overarching
      theme was desiring dialogue with the researcher. Presenting themselves as experts
      on living with pain because of a chronic disabling condition, respondents
      described personal experiences of living with pain, coping with pain, and
      educating others about pain. Examining comments and narratives written in the
      margins of quantitative survey questionnaires can add value to and extend
      understanding of survey findings and implications.

PMID- 16294806
TI  - Epidemiology, therapeutic agents and cost of management of paediatric malaria in
      a Nigerian tertiary hospital.
AB  - BACKGROUND AND OBJECTIVES: Malaria is the most widespread parasitic disease in
      sub-Saharan Africa with associated high morbidity and mortality especially among
      the highly predisposed population of pregnant women and children of age five
      years and below. Living in malaria endemic regions of the world has become
      associated with health and economic hazards placing financial and productive
      burden on affected households. METHODS: A prospective study of children treated
      for malaria and other associated illnesses at a Nigeria tertiary health
      institution between May and October 2003 was undertaken. The various malaria
      associated diseases treated were determined from their provisional diagnosis,
      hospital records and causative agents confirmed from their diagnostic laboratory
      results. Cost of treatment was determined from the patients' guardian and
      confirmed from relevant hospital departments. Common drugs for malaria treatment,
      their costs, relative effectiveness and frequency of use were determined through
      a completed questionnaire by health officers and patients' guidance. RESULTS: Of
      5356 paediatric patients suspected of having malaria, 5100 (95.2%) were confirmed
      positive for malaria parasites microscopically. Of these, 4119 (80.8%) were aged
      0 - 6 years, with children aged 1 to 3 years being mostly affected. Eight hundred
      and twenty (16.1%) of them were in-patients spending an average of six days on
      hospital bed. Over 22 million naira (dollar 0.22 m) was spent on the treatment of
      malaria with drugs accounting for the major cost (66.81%). About 33.7% of the
      patients had malaria complicated with other diseases. INTERPRETATION AND
      CONCLUSION: The effectiveness of common therapeutic agents used for malaria
      treatment, their costs and associated side effects is discussed. Recommendations
      are made for appropriate care and government subsidy for paediatric malaria
      management in sub-Saharan Africa.

PMID- 16294807
TI  - Larvicidal and mosquito repellent activities of Pine (Pinus longifolia, family:
      Pinaceae) oil.
AB  - BACKGROUND AND OBJECTIVES: Various plant-based products are safe and
      biodegradable alternatives to synthetic chemicals for use against mosquitoes. Oil
      of Pinus longifolia is traditionally used for protection against mosquitoes in
      some rural areas but there is no documented report of its use against mosquitoes.
      The present study was undertaken to scientifically evaluate the activity of Pine
      oil against mosquitoes. METHODS: The oil was procured from the market and its
      contents were chemically analysed. Larvicidal activity of oil was tested in
      laboratory bioassays, while repellent action was studied during whole night bait
      collections in field by direct application on the skin and after its impregnation
      on mats. RESULTS: Results showed varying degree of larvicidal activity of Pine
      oil against mosquitoes with LC50 values ranging between 82 and 112 ppm. The Pine
      oil had strong repellent action against mosquitoes as it provided 100% protection
      against Anopheles culicifacies for 11 h and 97% protection against Culex
      quinquefasciatus for nine hours respectively. Electrically heated mats prepared
      from Pine oil provided, 94 and 88% protection against An. culicifacies and Cx.
      quinquefasciatus for 10 and seven hours respectively. INTERPRETAION AND
      CONCLUSION: Pine oil is effective against mosquito larvae at very higher doses
      which are not of any practical utility. However, Pine oil showed strong repellent
      action against An. culicifacies (malaria vector) and Cx. quinquefasciatus (pest
      mosquito). Thus its use could be popularised as mosquito repellent.

PMID- 16294808
TI  - Monitoring of insecticides resistance in main malaria vectors in a malarious area
      of Kahnooj district, Kerman province, southeastern Iran.
AB  - BACKGROUND AND OBJECTIVES: Kahnooj district in south of Iran is an endemic area
      for malaria where Anopheles stephensi (Liston) is a main malaria vector and An.
      dthali (Patton) a secondary vector. According to the national strategy plan on
      monitoring of insecticides resistance, this study was performed on susceptibility
      and irritability levels of An. stephensi and An. dthali to different insecticides
      in the district. METHODS: The susceptibility and irritability levels of field
      strains of An. stephensi and An. dthali at the adult and larval stages to
      discriminative dose of different imagicides was determined as recommended by WHO.
      RESULTS: Using discriminative dose and WHO criteria it was found that An.
      stephensi is resistant to DDT and dieldrin with 36.1 +/- 2.3 and 62.2 +/- 1.95
      mortality rates, respectively; but susceptible to other insecticides. An. dthali
      was found to susceptible to all tested insecticides. The larvae of An. stephensi,
      exhibited 100% mortality for temephos and malathion, but 44 +/- 4.32 for
      discriminative dose of fenitrothion. The results of irritability level for DDT
      and pyrethroids showed that permethrin had the most irritancy effect on An.
      stephensi and An. dthali. DDT and deltamethrin showed the least irritancy effect
      against An. stephensi with 0.42 +/- 0.08 and 0.77 +/- 0.12 take-offs/min/adult,
      respectively, however, lambdacyhalothrin had the least irritancy effect against
      An. dthali with 0.096 +/- 0.02 take-offs/min/ adult. The mean number of take
      offs/min/adult with permethrin showed significant difference to DDT,
      lambdacyhalothrin, cyfluthrin and deltamethrin. INTERPRETATION AND CONCLUSION:
      Pyrethroid insecticides are being used as indoor residual sprays in Iran. Based
      on our results, the main malaria vectors in the region are still susceptible to
      pyrethroid insecticides. Therefore, we propose the use of pyrethroids with low
      irritancy effect in rotation with carbamate insecticides in two interval seasonal
      peaks of malaria transmission. Biological control including larvivorous fishes,
      using of local made Bacillus thuringiensis and larvicides such as chlorpyrifos
      methyl are the main larval control in the region. Result on larval test exhibited
      the susceptibility of main vectors to some larvicides, although the 100%
      mortality was not obtained using fenitrothion and this is postulated the use of
      this insecticide in agriculture pest control. Monitoring and evaluation of
      insecticides resistance in malaria vectors in the region could provide an
      essential clue for judicious use of insecticides.

PMID- 16294809
TI  - Efficacy of IGR compound Starycide 480 SC (Triflumuron) against mosquito larvae
      in clear and polluted water.
AB  - BACKGROUND AND OBJECTIVES: An environmental friendly formulation Starycide 480 SC
      (Triflumuron-OMS-2015 ), a new insect growth regulator with chitin synthesis
      inhibitor type mode of action was evaluated against mosquito larvae in laboratory
      and small-scale field trials carried out in and around Delhi. METHODS: The
      formulation was tested in laboratory for its bio-efficacy against late III instar
      mosquito larvae of different species using WHO bioassay procedure. In the field
      formulation was sprayed at doses of 0.3, 0.5 and 1 ppm (g/m3) in the natural
      breeding habitats of Anopheles and Culex mosquitoes. The impact was assessed by
      monitoring densities of larvae by dipper and observing the reduction in larval
      density and inhibition of adult emergence. RESULTS: In the laboratory,
      formulation was more effective against larvae of Anopheles stephensi and Aedes
      aegypti than Culex quinquefasciatus, but it produced 100% inhibition of adult
      emergence for all mosquito species at a concentration of 0.02 ppm. In the field
      trials, formulation did not produce 100% reduction in the density of late stage
      larvae even at 1 ppm (g/m3), the highest dose tested, but it resulted in 100%
      inhibition of pupal formation of both Anopheles and Culex spp in different types
      of habitats for 3-7 weeks even at a lower dose of 0.5 ppm. INTERPRETATION AND
      CONCLUSION: Application of triflumuron in the natural breeding habitats in both
      clean and polluted water @ 0.5 ppm (g/m3) resulted in complete inhibition of
      adult emergence of both Anopheles and Culex spp for 3-7 weeks. This formulation
      may be tested in large-scale field trials for further use in the vector control
      programme.

PMID- 16294810
TI  - Efficacy of synthetic pyrethroid and propoxur aerosol in the control of German
      cockroaches (Dictyoptera: Blatellidae) in cookhouses.
AB  - BACKGROUND AND OBJECTIVES: A field trial was carried out in cookhouses in an
      urban area to evaluate the efficacy of synthetic pyrethroid (0.02% deltamethrin +
      0.13% allethrin) and propoxur aerosols (2%) in the control of German cockroaches
      (Blatella germanica). METHODS: A total of six cookhouses were selected by simple
      random sampling method (two each for the two insecticide treatments and two for
      control). RESULTS: It was observed that 89.36-87.8 and 77.95-59.74% reductions
      were achieved with propoxur and synthetic pyrethroid treatment respectively by
      first week post-treatment. The reduction in propoxur treated areas by eight weeks
      post-treatment was 82.98-76.13%, whereas the reduction in the same time period in
      synthetic pyrethroid treated areas ranged from 14.36% to an increase in density
      by a phenomenal 157.86% in one of the treated sites. INTERPRETATION AND
      CONCLUSION: The study reports the efficacy of propoxur aerosol (2%) treatment
      over synthetic pyrethroid (0.02% deltamethrin + 0.13% allethrin) in the control
      of cockroach infestation in cookhouses in urban area.

PMID- 16294811
TI  - Awareness about dengue syndrome and related preventive practices amongst
      residents of an urban resettlement colony of south Delhi.

PMID- 16294812
TI  - [Evolution of cardiac pacing and electrical heart stimulation].

PMID- 16294813
TI  - [Side branch occlusion during direct stent implantation. Incidence and related
      factors].
AB  - AIM: The aim of the study was to evaluate the compromise of side branches when
      jailed by a coronary stent implanted without balloon predilation. PATIENTS AND
      METHODS: 56 patients in which at least a coronary stent was implanted without
      balloon predilation and covering a side brach (58 stents, 1.04 +/- 0.19 per
      patient) were studied. The effect of direct coronary stent implantation over side
      branch flow, as well as the characteristics associated were studied. RESULTS: The
      main vessel was left anterior descending in 63%, left circumflex in 21%, right
      coronary in 14%, and left main in one case. An angiographic successful result in
      the main vessel was obtained in all cases. Coronary flow was TIMI 3, 2, 1, and 0
      in 95%, 3%, 0%, and 2% before the procedure, in comparison with 86%, 2%, 3%, and
      9% after stent implantation (p = 0.204). The incidence of side branch occlusion
      was 12% (7/58). In one case, the side branch was dilated across the stent struts,
      and thus the rate of side branch loss at the end of the procedure was 10% (6/58).
      In cases of side branch occlusion, there was a more severe stenosis at its origin
      before stent implantation (30.2 +/-31.3% vs 16.8 +/- 11.1%, p = 0.028). Fifty
      percent of side branches occluded after direct coronary stent implantation and
      angiographically re-evaluated at follow-up became patent, and 88% of side
      branches not affected after stent implantation remained patent at 6.2+/-1.9
      months. CONCLUSION: The rate of side branch occlusion after direct stent
      implantation in our series was 12%, that is not different from that reported for
      conventional stent implantation. Thus, the decision of using direct or
      conventional coronary stenting should not be conditioned by the presence of side
      branches arising from the target lesion.

PMID- 16294814
TI  - [Impact of the intra-aortic balloon pump in the mortality due to cardiogenic
      shock secondary to acute myocardial infarction].
AB  - OBJECTIVE: To determine the impact of the intra-aortic balloon pump in the
      mortality due to cardiogenic shock post-acute myocardial infarction. METHODS: In
      a two-year period, 292 patients with acute myocardial infarction were admitted to
      the coronary intensive care unit, 40 were included in the study. Afterwards,
      patients were divided in two groups: early cardiogenic and late cardiogenic
      shock, and they were assigned randomly and blind to treatment with inotropics and
      inotropics plus intra-aortic balloon pump. RESULTS: There were significant
      differences in the measurements of pulmonary wedge pressure (20.4 +/- 1.6 vs 24.4
      +/- 1.50, p = 0.0004) and the cardiac index (2.06 +/- 0.7 vs 1.65 +/- 0.18, p =
      0.0002) between the two groups. The late cardiogenic shock group showed an
      increased mortality (25.9% vs 61.5%, p < 0.05). Patients treated with inotropics
      + balloon, in both early and late shock groups, showed a reduction in mortality
      of 66% and 69%, respectively. CONCLUSIONS: The use of the intra-aortic balloon
      pump in the treatment of cardiogenic shock post acute myocardial infarction
      reduces the mortality when associated with the use of inotropics and reperfusion.

PMID- 16294815
TI  - [Synthetic membrane coronary stent graft in coronary disease].
AB  - The use of a synthetic membrane-covered stent has been suggested to overcome some
      specific lesions in coronary arteries and to solve some potential complications
      that could arise in any procedure of coronary intervention. A synthetic membrane
      coronary stent graft (JOSTENT-JOMED) is constituted by a membrane of
      polytetrafluoroethylene (PTFE), fixed between two thin metallic stents. In this
      clinical review of our laboratory's experience, the Jostent graft was used in
      several angiographic circumstances in coronary arteries or in vein grafts. Our
      clinical experience consists of 17 patients that were treated with placement of
      PTFE stents for different indications: coronary rupture in two patients; thrombus
      and degenerative vein grafts in eight patients, coronary aneurysms in four
      patients, and thrombus in coronary arteries in three more. Our clinical results
      with this device suggest that its implant is feasible and safe with a clinical
      success of 100% without complications during in-hospital stay; during the
      clinical 11 +/- 3 months follow-up, only three patients exhibited major cardiac
      events. The indication for PTFE stent in vein grafts with degenerative and
      thrombus lesions has not been determined yet; however, recently, some randomized
      trials have shown little benefit in this circumstance. On the other side,
      coronary vessel rupture and coronary aneurysms are currently the most definitive
      indications.

PMID- 16294816
TI  - [Results after placement of coronary stents in protected and not protected
      coronary trunk vs revascularization surgery].
AB  - INTRODUCTION: We analyzed the clinical and angiographic results, as well as the
      follow-up of patients with left coronary trunk disease (LCT) subjected to
      percutaneous transluminal coronary angioplasty (PTCA) with stenting and compared
      them with those subjected to myocardial revascularization surgery (MRV). MATERIAL
      AND METHODS: From May 1998 to October 2003, 3,680 procedures were performed in
      2,900 patients; 30 of them were selected to form group PTCA, 17 protected with
      stenting and 13 not protected, as they were not suited for surgery due to
      inappropriate bedding and rejection by the patient. Another group of 30 patients
      (MRV) with coronary bypass, average of 3.2 grafts. Age ranged from 45 to 74 years
      (65.7 +/- 11.5) for the PTCA and for MRV from 49 to 77 years (66.9 +/- 7.1); 25
      men (83%) in the PTCA group and 23 men (76%) in the MRV group. Systemic arterial
      hypertension in both groups: 10 (33%), smoking in both groups: 17 (56%); diabetes
      mellitus PTCA: 11 (36%) and MRV: 3 (10%); hypercholesterolemia PTCA: 19 (63%),
      MRV 9 (30%); unstable angina according to the Canadian Society of Cardiology
      (CSC) for PTCA: 17 (56%), MRV; 16 (53%); multivascular disease in both groups: 20
      (66%). Average percentage of obstruction was of 90 +/- 6.3%. FE for PTCA, 30 to
      55% (40.3 +/- 8.7) and for MRV, 38 to 67% (48.6 +/- 6.1). RESULTS: Immediate
      success in 26 patients (87%) for the PTCA group and in 28 patients (90%) for the
      MRV group. COMPLICATIONS: PTCA, 4 (13%) and MRV, 20 (66%). Perioperative IAM for
      PTCA, 2 (6%) and for MRV, 8 (26%). Mortality in the PTCA group was of 4 patients
      (13%) and in the MRV group of 3 (10%). Follow-up for PTCA, 19.4 months, for MRV
      of 20 +/- 3, obtained in 26 of the whole group. Late survival adverse events
      (DEATH or IAM): PTCA, 25 (83.3%), one patient with IAM; MRV, 20 (66.6%), one
      patient died during the follow-up period. CONCLUSIONS: Placement of stents in the
      left coronary trunk disease is a feasible procedure as an alternative for
      myocardial revascularization, with a low rate of complications in cases of
      conserved ventricular function despite their higher risk profile.

PMID- 16294817
TI  - [Ambulatory pacemaker surgery].
AB  - The chronic cardiac stimulation is know since 1958, pacemaker implant was
      considered a difficult procedure that was performed through cardiovascular
      surgery and the patient required several in hospital days. On the grounds of new
      surgical techniques and development of new materials for pacemakers, as well as
      the rise of Ambulatory Surgery and its application in pacemaker implants, the
      hospital stay and consequently, costs have decreased significantly. In 1986,
      Zegelman reported 583 patients subjected to ambulatory pacemaker surgery without
      mortality. The purpose of this report it to evaluate the efficacy and safety of
      ambulatory pacemaker surgery. One hundred seventy seven patients from an
      ambulatory program and 95 from a traditional program were included.
      Hospitalization time was 15.7 +/- 15.1 hours in the first group and 238 +/- 188
      hours for the second, prevalence of complications was 2.2% in the 272 patients.
      Complications for both groups were similar and were solved, without mortality. We
      conclude that the ambulatory pacemaker surgery is effective and safe for patients
      and is cheaper for hospitals. The success of this program depends on the number
      of implants in each hospital and the operator's experience.

PMID- 16294818
TI  - [Short-term results of rescue angioplasty in patients with acute myocardial
      infarction and failure of thrombolysis treatment].
AB  - The present study is aimed at describing the short-term assessment of clinical
      and angiographic results in patients with acute myocardial infarction treated
      with rescue percutaneous transluminal coronary angioplasty (RPTCA). METHODS: We
      reviewed retrospectively, from January 2001 to July 2004, the interventional
      procedures performed in patients with coronary heart disease. From a total of
      3,258 patients we selected 32 (0.98%) with acute myocardial infarction and
      failure of thrombolysis treatment, which were treated with RPTCA to relief the
      symptoms. Average age was 63 years (range 47-79), there were 24 men (75%);
      hypertension in 29 (90.6%); diabetes mellitus in 18 (56.3%); currently smoking 24
      (75%); dyslipidemia in 11 (34.4%); unstable angina in 9 (28.1%); previous
      myocardial infarction in 2 (6.3%). The area related to the infarction was
      anterior and lateral in 14 (43.8%), anteroseptal in 6 (18.8%), postero-inferior
      in 5 (15.6%) with electric and hemodynamic involvement in 4 (12.5%), lateral in 1
      (3.1%). Thrombolysis treatment was delivered in 3.19 hours (range 2-7 hours) with
      streptokinase in 19 (59.4%) and rTPA in 13 (40.6%). The evaluated serum marker
      was CPK-MB with the highest level of 348 +/- 240 U/L. Killip Kimball (KK) class
      was established as follows: KKI in 5 (15.6%), II in 16 (50%), III in 5 (15.6%),
      and IV in 6 (18.8%). Patients with cardiogenic shock were treated with intra
      aortic balloon counter-pulsation. RESULTS: Time between symptoms and arrival to
      the cath lab was 11 hours (range 6-24 hours). TIMI flow was: TIMI 0 in 16 (50%).
      TIMI 1 in 10 (31.2%), TIMI 2 in 6 (18.8%). The number of vessels with a
      significant lesion was 1.9 (range 1-4). Stents were placed in 27 (84.3%)
      patients. Angiographic success postangioplasty was achieved in 24 (75%); there
      were 9 complications (28.1%), no reflow in 7 (21.8%), coronary dissection in 1
      (3.1%). Six patients died (18.7%) and 4 of them (12.5%) were in cardiogenic
      shock. CONCLUSION: RPT-CA is a high-risk procedure, being an acceptable treatment
      option for patients with thrombolysis failure.

PMID- 16294819
TI  - [Percutaneous closure of patent foramen ovale with amplatzer device. Report of
      two cases].
AB  - OBJECTIVE: We present two cases of Patent Foramen Ovale (PFO) treated with
      percutaneous Amplatzer device. METHOD: The first case corresponds to 48 years old
      woman with Ebstein's disease with moderate to severe hemodynamic repercussion and
      three cerebrovascular accidents, the last one under coumarin treatment, she
      received antiarrhythmic medication and despite of it developed 1st degree AV
      block, supraventricular and ventricular ectopia, rigth branch block. The second
      case corresponds to a 22 years old man with antecedents of cerebrovascular
      accident at the age of 21 with sequelae of convulsive crisis. Both patients were
      percutaneously treated with Amplatzer devices. The first patient was treated with
      a foramen ovale device and second with septal occluder due to the diameter of the
      foramen. Both patients have remained asymptomatic during the follow-up period.
      CONCLUSIONS: The PFO devices are indicated for patients with a history of
      cerebrovascular accidents.

PMID- 16294820
TI  - [Coronary aneurysms not associated to stenosis of coronary arteries. Conservative
      treatment and evolution in six patients].
AB  - Coronary artery aneurysms are a relatively infrequent finding with an incidence
      of 1-2% per year. The most frequent cause is atherosclerosis and, in that case,
      they are always associated to stenosis of coronary arteries. We reviewed the
      coronary angiographic studies performed in the past seven years and we identified
      six patients that were admitted with an acute coronary syndrome, whose
      angiographic studies showed the presence of aneurysms in, at least, one of the
      coronary arteries. In these patients, we found no relation between aneurysms and
      distal or proximal stenosis. Although there was no angiographic evidence of
      classical coronary atherosclerosis, we think that atherosclerotic disease could
      have been the etiological cause, due to injury of the endothelium and media by
      deposits of lipids, smooth muscle cells, collagen, macrophages, and T-lymphocytes
      that would have damaged the adventitia layers of the vessel wall, stimulating
      "vasa-vasorum" neovascularization. The evolution of coronary aneurysms without
      associated stenosis in the same coronary artery and without another potentially
      treatable cause is unknown. Due to the limited literature regarding this issue
      and, taking into account our experience, we feel that, in these cases, medical
      treatment might be a good option as we detected no major cardiac events in any
      patient at mid and long-term follow up.

PMID- 16294821
TI  - [Implantation of a pacemaker through persistent left superior vena cava].
AB  - Persistent left superior vena is a relatively rare congenital variant. It is,
      however, the most common variation of the thoracic venous system. Prevalence is
      estimated in about 0.6 to 1.0% during pacemaker placement. This finding, often
      incidental, can difficult the lead progression through the left jugular or
      subclavian routes. This report describes a case of successful pacemaker
      implantation through a persistent left superior vena. Technical difficulties were
      overcome using the pacemaker electrode as unipolar lead. Endocavitary ECG
      recording helped us to guide the lead through the tortuous anatomy. A stable lead
      position was finally achieved by means of the active fixation system of the
      pacemaker electrode.

PMID- 16294822
TI  - [Percutaneous closure of ductus arteriosus and muscular ventricular defect with
      amplatzer occluder in a patient with severe pulmonary hypertension].
AB  - Surgical treatment of multiple muscular ventricular septal defects with
      associated lesions and severe pulmonary hypertension has a high morbility and
      mortality. Closure of these defects by the Amplatzer muscular VSD occluder is an
      alternative to surgery, avoiding the need of cardiopulmonary bypass. We present
      the case of a 38 year-old woman with signs of heart failure in NYHA functional
      class IV, with two muscular ventricular septal defects, patent ductus arteriosus
      and severe pulmonary hypertension, that were treated with three Amplatzer
      muscular VSD occluders, with significant reduction of pulmonary pressure and
      functional class improvement.

PMID- 16294824
TI  - [Coronary physiology and its usefulness for the interventionist cardiologist:
      invasive measurement of coronary flow-pressure].
AB  - One of the most important limitations of coronary angiography is the inability to
      characterize the physiological significance of an intermediate coronary stenosis.
      Measuring coronary blood flow and pressure provides unique information that
      complements anatomic evaluation and facilitates decision-making in the cardiac
      catheterization unit. This review discusses the fundamental concepts of coronary
      physiology, methodology, and clinical applications of coronary and flow
      measurements.

PMID- 16294823
TI  - [Percutaneous closure of ventricular septal defect by Amplatzer occluder.
      Immediate and mid-term follow up results].
AB  - OBJECT: To report the immediate and mid-term follow-up results of the Amplatzer
      membranous VSD occluder for the percutaneous occlusion of the perimembranous VSD.
      BACKGROUND: Percutaneous perimembranous VSD occlusion is still considered an
      experimental method where a variety of devices have been tested. Nowadays, more
      than 500 membranous Amplatzer devices have been implanted worldwide with
      encouraging results. METHOD: We included 6 patients (1 man and 5 women) with a
      mean age of 9.9 years (range, 3 to 17.5) in whom percutaneous perimembranous VSD
      closure was attempted. RESULTS: In one of the patients, positioning of the device
      was not possible (intention to treat success rate, 83.3%). In the remaining five
      patients, there was a single defect. The VSD mean diameter with echo was 7 +/-
      1.7 mm (range, 5.1 to 9) and with angio was 6.9 +/- 1 (range, 6 to 8). Mean
      pulmonary pressure was 20.2 +/- 7.7 mm Hg (range, 12-30) and Qp/Qs was 1.69 +/-
      0.65 (range, 1.2-2.8). A single device was use in all cases. Immediate
      angiographic control showed complete occlusion in two patients, trivial shunt in
      one, and mild shunt in two. Follow-up was at least 4 months. Only one patient has
      residual trivial shunt, the rest of the defects are completely closed.
      CONCLUSION: The special design of the Amplatzer membranous VSD occluder allows
      percutaneous closure of this defect in a safe and effective way, with good mid
      term results. In selected cases, this is a good alternative to surgery in the
      treatmen of this cardiac defect.

PMID- 16294825
TI  - [Percutaneous mitral valvuloplasty].
AB  - Pure mitral stenosis has a bad prognosis due to progressive narrowing of the
      mitral orifice, which requires surgical techniques to widen it. Among these
      procedures are open heart surgery and the percutaneous approach through balloon
      valvuloplasty. This article is an update of the indications and on the use of
      echocardiography for patient selection. It describes transeptal puncture and
      analyses the advantages and disadvantages of the different interventional
      techniques with: one balloon, emphasizing on a technique modified by us, i.e., th
      use of Nucleus balloon; with Inoue balloon, double balloon technique, and
      Cribier's valvulotomy, which is not performed in our country because no
      valvulotome is currently available. We analyze the success rate, which is of 100%
      when considering any increase in valvular area and of 61% in unfavorable
      patients, taking as a success parameter a 50% increase in the original valvular
      area and a decrease of the transvalvular gradient to less than 10 mm Hg. We
      comment about procedure complications, such as severe valvular regurgitation,
      interatrial shunt and tamponade. Procedure mortality is of 1%, especially when
      the valvular area is small-es than 0.7 cm2 or the Wilkins score is over 13.

PMID- 16294826
TI  - [Role of the transcription factor NF-kappaB in the cardiac cell].
AB  - The signaling pathways that control the life-death switch of a cell are a prime
      interest in Modern Biology. To this respect, NF-kappaB has emerged as a decisive
      transcription factor in the cell's response to apoptotic challenge and its
      effects on apoptosis have far-reaching consequences for normal development and/or
      homeostasis in many cells and tissues, including the immune system, hair
      follicles, and epidermal appendages, the liver, and nervous system. In this
      review we analyze the pivotal role of the transcription factor NF-kappaB in the
      normal functioning of the cardiac cell and its implication on some of the most
      frequent cardiac pathologies, such as ischemia-reperfusion injury, ischemic
      precondition, hypertrophy, atherosclerosis and cardiac arrest. While NF-kappaB is
      commonly found to be cytoprotective, there are a number of instances where it is
      proapoptotic depending on the inducing stimulus and the cell context. Significant
      progress has been made in understanding its mode of action and its interplay with
      other key factors. These studies identified many anti- and pro-apoptotic NF
      kappaB regulated genes that mediate its activity, these important new insights
      fuel hope that novel approaches will be developed to control the effects of NF
      kappaB in cardiac pathologies.

PMID- 16294827
TI  - [Ventricular septal defect and aortic valvular endoarteritis, cause of systemic
      and pulmonary embolism].

PMID- 16294828
TI  - Bioactive compounds from cyanobacteria and microalgae: an overview.
AB  - Cyanobacteria (blue-green algae) are photosynthetic prokaryotes used as food by
      humans. They have also been recognized as an excellent source of vitamins and
      proteins and as such are found in health food stores throughout the world. They
      are also reported to be a source of fine chemicals, renewable fuel and bioactive
      compounds. This potential is being realized as data from research in the areas of
      the physiology and chemistry of these organisms are gathered and the knowledge of
      cyanobacterial genetics and genetic engineering increased. Their role as
      antiviral, anti-tumour, antibacterial, anti-HIV and a food additive have been
      well established. The production of cyanobacteria in artificial and natural
      environments has been fully exploited. In this review the use of cyanobacteria
      and microalgae, production processes and biosynthesis of pigments, colorants and
      certain bioactive compounds are discussed in detail. The genetic manipulation of
      cyanobacteria and microalgae to improve their quality are also described at
      length.

PMID- 16294829
TI  - Microbial biomass estimation.
AB  - The development of a fully automated on-line monitoring and control system is
      very important in bioprocesses. One of the most important parameters in these
      processes is biomass. This review discusses different methods for biomass
      quantification. A general definition of biomass and biovolume are presented.
      Interesting concepts about active but not culturable cells considerations are
      included as well as concepts that must be taken into account when selecting
      biomass quantification technology. Chemical methods have had few applications in
      biomass measurement to date; however, bioluminescence can selectively enumerate
      viable cells. Photometric methods including fluorescence and scattered light
      measurements are presented. Reference methods including dry and wet weight,
      viable counts and direct counts are discussed, as well as the physical methods of
      flow cytometry, impedancimetric and dielectric techniques.

PMID- 16294830
TI  - Use of algae for removing heavy metal ions from wastewater: progress and
      prospects.
AB  - Many algae have immense capability to sorb metals, and there is considerable
      potential for using them to treat wastewaters. Metal sorption involves binding on
      the cell surface and to intracellular ligands. The adsorbed metal is several
      times greater than intracellular metal. Carboxyl group is most important for
      metal binding. Concentration of metal and biomass in solution, pH, temperature,
      cations, anions and metabolic stage of the organism affect metal sorption. Algae
      can effectively remove metals from multi-metal solutions. Dead cells sorb more
      metal than live cells. Various pretreatments enhance metal sorption capacity of
      algae. CaCl2 pretreatment is the most suitable and economic method for activation
      of algal biomass. Algal periphyton has great potential for removing metals from
      wastewaters. An immobilized or granulated biomass-filled column can be used for
      several sorption/desorption cycles with unaltered or slightly decreased metal
      removal. Langmuir and Freundlich models, commonly used for fitting sorption data,
      cannot precisely describe metal sorption since they ignore the effect of pH,
      biomass concentration, etc. For commercial application of algal technology for
      metal removal from wastewaters, emphasis should be given to: (i) selection of
      strains with high metal sorption capacity, (ii) adequate understanding of
      sorption mechanisms, (iii) development of low-cost methods for cell
      immobilization, (iv) development of better models for predicting metal sorption,
      (v) genetic manipulation of algae for increased number of surface groups or over
      expression of metal binding proteins, and (vi) economic feasibility.

PMID- 16294832
TI  - You are in charge! From defining "reality" to generating consensus, how we
      understand the world around us.

PMID- 16294831
TI  - Perspectives in the modeling and optimization of PHB production by pure and mixed
      cultures.
AB  - Poly(beta-hydroxybutyrate) or PHB is an important member of the family of
      polyhydroxyalkanoates with properties that make it potentially competitive with
      synthetic polymers. In addition, PHB is biodegradable. While the biochemistry of
      PHB synthesis by microorganisms is well known, improvement of large-scale
      productivity requires good fermentation modeling and optimization. The latter
      aspect is reviewed here. Current models are of two types: (i) mechanistic and
      (ii) cybernetic. The models may be unstructured or structured, and they have been
      applied to single cultures and co-cultures. However, neither class of models
      expresses adequately all the important features of large-scale non-ideal
      fermentations. Model-independent neural networks provide faithful representations
      of observations, but they can be difficult to design. So hybrid models, combining
      mechanistic, cybernetic and neural models, offer a useful compromise. All three
      kinds of basic models are discussed with applications and directions toward
      hybrid model development.

PMID- 16294833
TI  - Atypical antipsychotics: special formulations for acute agitation.

PMID- 16294834
TI  - The ultimate deception: childhood sexual abuse in the church.
AB  - Childhood sexual abuse is a serious problem. Significant evidence exists that
      victims experience both short-term and long-term emotional and psychological
      problems related to the abuse. Childhood sexual abuse committed by clergy or
      other adults affiliated with the church may have additional ramifications because
      of deep violations of trust, honesty, and love. In addition, it can create
      spiritual distress in victims. Child and adolescent mental health nurses need to
      actively promote risk-reduction strategies to help prevent the abuse from
      occurring in their communities.

PMID- 16294835
TI  - Facilitating communication: how to truly understand what patients mean.
AB  - 1. Patients experience greater satisfaction with nursing care when they are truly
      understood. 2. Being aware of taken-for-granted meanings and committing the time
      to seek clarification and explore meanings are two basic principles that can
      facilitate understanding. 3. Techniques nurses can use to facilitate
      understanding include restating what was heard to ensure understanding and to
      demonstrate active listening, asking open-ended questions, and checking for
      understanding.

PMID- 16294836
TI  - Effects of sexuality on lesbians' experiences of depression.
AB  - 1. Lesbians are members of every racial, ethnic, and socioeconomic group. 2. Very
      little is known about depression in lesbians, and thus far, study findings are
      conflicting. However, depression in lesbians seems to be underpinned by
      relationship issues and levels of social support. 3. Caring for lesbian clients
      requires nurses to think holistically, understand their clients' sexuality within
      the context of their life experiences, and demonstrate respect and acceptance.

PMID- 16294837
TI  - Post-infidelity stress disorder.

PMID- 16294838
TI  - The lessons of Katrina.

PMID- 16294839
TI  - Zebra mussels reroute contaminant flow through food chain.

PMID- 16294841
TI  - How a global-warming skeptic became famous.

PMID- 16294840
TI  - More sources of mercury in the environment.

PMID- 16294842
TI  - Sunlight turns landfill gas into hydrogen.

PMID- 16294843
TI  - Where have all the fish gone? The reasons why fish catches in Swiss rivers are
      declining.

PMID- 16294844
TI  - Characteristics of metals in nano/ultrafine/fine/coarse particles collected
      beside a heavily trafficked road.
AB  - Fine particles emitted from vehicles have adverse health effects because of their
      sizes and chemical compositions. Therefore, this study attempted to characterize
      the metals in nano (0.010 < Dp < 0.056 microm), ultrafine (Dp < 0.1 microm), fine
      (Dp < 2.5 microm), and coarse (2.5 < Dp < 10 microm) particles collected near a
      busy road using a microorifice uniform deposition impactor (MOUDI) and a Nano
      MOUDI. The nano particles were found to contain more of traffic-related metals
      (Pb, Cd, Cu, Zn, Ba, and Ni) than particles of other sizes, although crustal
      metals accounted for over 90% of all the particulate metals. Most crustal metals,
      Ba, Ni, Pb, and Zn in ultrafine particles displayed Aitken modes due to their
      local origins. The Ag, Cd, Cr, Ni, Pb, Sb, V, and Zn were 37, 50, 28, 30, 24, 64,
      38, and 22% by mass, respectively, in < 0.1-microm particles, with submicron mass
      median diameters (MMDs) in PM(0.01-18) (except Zn) (particularly the < 0.1-microm
      MMDs for Cd and Sb). These levels raise potential health issues. Particle-bound
      Zn was more abundant in the accumulation mode than in the nucleation/condensation
      mode, but the opposite was true for Ag, Cd, and Sb. The Ag, Ba, Cd, Pb, Sb, V,
      and Zn contents in nano particles were strongly associated with diesel fuel,
      while the Cu, Mn, and Sr in particles < 0.1 microm were more strongly associated
      with gasoline. The high content of Si in nano particles, more associated with
      diesel soot than with gasoline exhaust, is another health concern.

PMID- 16294845
TI  - Tracking toxaphene in the North American Great Lakes basin. 1. Impact of
      toxaphene residues in United States soils.
AB  - A coupled atmospheric transport model was employed to study six scenarios to
      assess the contribution of reemission and long-range transport of toxaphene from
      different sources in the United States to its environmental fate in the Great
      Lakes ecosystem in the year 2000. Modeled air concentrations at the first model
      level (1.5 m) range from less than 5 pg m(-3) over the upper Great lakes (Lakes
      Superior and Huron) to several tens of picograms per cubic meter over the lower
      Great Lakes (Lakes Erie and Ontario) in the summer but drop off to the range from
      0.05 to 2 pg m(-3) in the wintertime. The modeled toxaphene depositions to the
      lakes suggest a decreasing trend from the mid-1990s to 2000. Modeling results
      showed that, on an annual basis, for the Great Lakes basin as a whole, the
      southeast U.S. sources made the largest contribution to the toxaphene air
      concentrations and dry and wet depositions at 72%, 78%, and 88% respectively. The
      model results also showed that a significant proportion of these contributions
      occur during relatively short episodic events due primarily to the interseasonal
      changes in atmospheric circulation patterns.

PMID- 16294846
TI  - Tracking toxaphene in the North American Great Lakes basin. 2. A strong episodic
      long-range transport event.
AB  - In this paper we examine the modeled daily toxaphene air concentrations from
      September 9 to 13, 2000, during which air concentration levels were 2-3 orders of
      magnitude higher than those derived from in situ measurements around the Great
      Lakes during the same year and during the 1990s. Meteorological conditions
      revealed that a typical deformation flow system associated with a high-pressure
      system extending from the east coast of Canada to the southern United States was
      one of the critical elements that enabled the transport of toxaphene to the Great
      Lakes. Cloud bands seen on satellite imagery and the rain band predicted by an
      atmospheric forecast model indicate that the system also delivered warm and humid
      air from the Gulf of Mexico and the southern United States to the Great Lakes.
      This resulted in strong wet deposition of toxaphene to the lakes. Substantial
      increase in the air concentration of toxaphene over the Great Lakes in this short
      period contributed greatly to raising the annual average daily air concentration
      for all of 2000. The results suggest that such an episodic event could be a major
      pathway for atmospheric transport of toxaphene from the southern United States to
      the Great Lakes.

PMID- 16294847
TI  - Fluorescence spectroscopy reveals ubiquitous presence of oxidized and reduced
      quinones in dissolved organic matter.
AB  - Excitation-emission matrixes (EEMs) of 379 dissolved organic matter (DOM) samples
      from diverse aquatic environments were modeled by parallel factor analysis
      (PARAFAC). Thirteen components likely representing groups of similarly
      fluorescing moieties were found to explain the variation in this data set. Seven
      of the thirteen components were identified as quinone-like based on comparison of
      their excitation and emission spectra to spectra of model quinones. These quinone
      like fluorophores were found to vary in redox state and degree of conjugation.
      Two components were identified as amino acid-like based on comparison to tyrosine
      and tryptophan fluorescence spectra. The other four components are not yet
      associated with any class of molecules. The quinone-like fluorophores account for
      about 50% of the fluorescence for every sample analyzed, showing that quinone
      like fluorophores are an important and ubiquitous fluorescing moiety and in
      natural waters. Further, the distribution of the quinone-like fluorophores was
      evaluated as a function of environmental and laboratory redox gradients. Under
      reducing conditions, the contribution of the reduced quinone-like fluorophores
      increased concurrentwith a decrease in the oxidized quinone-like fluorophores,
      indicating that DOM fluorescence is a function of redox state of quinone-like
      moieties. Lastly, a ratio of two quinone-like fluorophores was found to explain
      the variation in the fluorescence index. These results provide new insight into
      the redox reactivity of DOM and have implications for the application of
      fluorescence spectroscopy as a tool to characterize DOM.

PMID- 16294848
TI  - Enhanced deposition and bioaccumulation of mercury in Antarctic terrestrial
      ecosystems facing a coastal polynya.
AB  - Mercury emitted by anthropogenic and natural sources occurs in the atmosphere
      mostly in the gaseous elemental form, which has a long lifetime in tropical and
      temperate regions. Once deposited in terrestrial and aquatic ecosystems the metal
      is partly re-emitted into the air, thus assuming the characteristics of global
      pollutants such as persistent volatile chemicals. In polar regions, during and
      after the sunrise, the photochemically driven oxidation of gaseous Hg by reactive
      halogens may result in areas of greatly enhanced Hg deposition. Mercury
      concentrations in soils, lichens, and mosses collected in a stretch between 74
      degrees 30' S and 76 degrees 00' S, in ice-free coastal areas of Victoria Land
      facing the Terra Nova Bay coastal polynya, were higher than typical Antarctic
      baselines. The finding of enhanced Hg bioaccumulation in Antarctic terrestrial
      ecosystems facing a coastal polynya strongly supports recent speculations on the
      role of ice crystals ("frost flowers") growing in polynyas as a dominant source
      of sea salt aerosols and bromine compounds, which are involved in springtime
      mercury depletion events (MDEs). These results raise concern aboutthe possible
      environmental effects of changes in regional climate and sea ice coverage, and on
      the possible role of Antarctica as a sink in the mercury cycle.

PMID- 16294849
TI  - Importance of automobile exhaust catalyst emissions for the deposition of
      platinum, palladium, and rhodium in the northern hemisphere.
AB  - An estimated 500 million vehicles worldwide are equipped with an exhaust catalyst
      that uses platinum group elements (PGE) as the main active components and thus
      contribute to global PGE emissions. Although PGE emitted from automobile exhaust
      catalysts were first believed to remain in the roadside environment, we propose
      here that fine PGE-containing particles in automobile exhaust have resulted in a
      widespread distribution of emitted PGE. Regional and long-range transport of PGE
      from automobile exhaust catalysts is supported by elevated PGE deposition in both
      a peat bog located 250 m from traffic and in central Greenland, respectively.
      Russian smelters were also found to contribute to PGE contamination in central
      Greenland. Deposition rates estimated for the roadside environment, the peat bog,
      and central Greenland were used to provide a first estimate of PGE deposition in
      the northern hemisphere. The results show that deposition of regionally or long
      range transported PGE accounts for a large fraction of total PGE deposition, and
      PGE deposition in the roadside environment represents less than 5% of the total
      deposition. Transport at the regional and global scales represents an important
      component in the environmental cycle of emitted PGE and needs to be further
      studied to fully assess the environmental fate of PGE from automobile exhaust
      catalysts.

PMID- 16294850
TI  - Current-use and legacy pesticide history in the Austfonna Ice Cap, Svalbard,
      Norway.
AB  - The Svalbard archipelago in arctic Norway receives considerable semivolatile
      organic contaminant (SOC) inputs from the atmosphere. To measure the history of
      net SOC accumulation there, we analyzed the upper 40 m of an ice core from
      Austfonna, the largest ice cap in Eurasia, for several legacy organochlorine (OC)
      compounds and current-use pesticides (CUPs) including organophosphorus (OP),
      triazine, dinitroaniline, and chloroacetamide compounds. Five OP compounds
      (chlorpyrifos, terbufos, diazinon, methyl parathion, and fenitrothion), two OCs
      (methoxychlor and dieldrin), and metolachlor--an herbicide--had historical
      profiles in the core. The highest OC concentration observed was aldrin (69.0 ng
      L(-1)) in the surface sample (1992-1998). The most concentrated OP was dimethoate
      (87.0 ng L(-1)) between 1986 and 1992. The surface sample also had highest
      concentrations of pendimethalin (herbicide, 18.6 ng L(-1)) and flutriafol, the
      lone observed fungicide (9.6 ng L(-1)). The apparent atmospheric persistence of
      CUPs likely results from little or no oxidation by OH* during the dark polar
      winter and in spring. Long-range atmospheric pesticide transport to Svalbard from
      Eurasia is influenced by the positive state of the North Atlantic Oscillation
      Index since 1980 and also by occasional fast-moving summer air masses from
      northern Eurasian croplands.

PMID- 16294851
TI  - Distribution and mass inventory of total dichlorodiphenyldichloroethylene in the
      water column of the southern California bight.
AB  - A large-scale survey on the area and depth stratified distribution of
      dichlorodiphenyltrichloroethane (DDT; mainly p,p'- and o,p'
      dichlorodiphenyldichloroethylene (DDE)) contamination in the water column of the
      Southern California Bight (SCB) was conducted in 2003-2004 using a solid-phase
      microextraction-based sampling technique. Dissolved-phase DDEs were clearly
      widespread, with the central SCB containing the highest levels, and the Palos
      Verdes Shelf sediments have remained the dominant source of DDT compounds to the
      SCB. The p,p'- and o,p'-DDE concentrations ranged from < 0.073 to 2.6 ng/L and
      from < 0.043 to 0.26 ng/L, respectively, clearly elevated with respect to
      measured values from across the globe. DDEs were hypothesized to have been
      transported from the historically contaminated zone on the Palos Verdes Shelf to
      other areas via a repeated process of sediment resuspension/deposition and short
      range advection. Total mass inventories were estimated at 14 and 0.86 kg for p,p'
      and o,p'-DDE, respectively, for the sampled area, resulting in p,p'- and o,p'
      DDE mass inventories for the entire SCB of 230 and 14 kg, respectively.
      Furthermore, total fluxes of p,p'-DDE were estimated to be in the range of 0.8 to
      2.3 metric tons per year. These results suggest that the SCB has been and
      continues to be a significant source of DDT contamination to the global oceans.

PMID- 16294852
TI  - Novel approach to identifying supersaturated metastable ambient aerosol
      particles.
AB  - Atomic force microscopy (AFM) was used to determine the shape of fine and
      ultrafine ambient aerosol particles with sizes between 25 and 700 nm after soft
      landing on a solid substrate. The particles were collected in summer during
      daytime at a relative humidity around 50%. To avoid kinetically induced
      deformation, as previously observed using high-velocity sampling in impactors,
      the particles were collected on pore filters at very low face velocities (on the
      order of 10 cm/s). The shape of the collected particles was quantified in terms
      of their height and apparent diameter. The amount of broadening introduced by the
      pyramidal shape of the nonideally sharp AFM tips was calibrated using Latex
      reference spheres with a range of diameters. The height-to-diameter ratios, H/D,
      of the collected aerosol particles could be extracted from the measured data.
      Specified in terms of volume-equivalent (dry) diameters, Dv, the size selected
      frequency distributions of the H/Dv-ratios were found to be bimodal. A small mode
      centered at H/Dv = 1.0 +/- 0.1 is attributed to nonhygroscopic particles that
      retained their shape after deposition on the substrate. The large mode, with a
      peak at H/Dv = 0.65 +/- 0.05, reflects soft particles which were strongly
      deformed due to vertical collapse after deposition. The pronounced deformation
      suggests that these particles had previously experienced deliquescence and, when
      collected at a comparatively low humidity, were in a metastable, supersaturated
      aqueous state. After landing and indoor sample storage the water evaporated,
      resulting in minimum H/Dv-ratios as low as 0.45. The dried metastable fraction
      amounted to 81 +/- 12% in the size range 150 < Dv < 700 nm, and 79 +/- 10% for 50
      < or = Dv < or = 150 nm, but only 26 +/- 10% for Dv < 50 nm. Comparison with
      recently reported data suggests that the observed metastable fraction is the same
      as the hygroscopic fraction identified by other means. The interpretation is
      further substantiated by a comparison of the size distributions of collected and
      airborne particles.

PMID- 16294853
TI  - Mercury emissions from cement-stabilized dredged material.
AB  - Upland placement of dredged materials from navigation channels in the New
      York/New Jersey Harbor is currently being used to manage sediments deemed
      inappropriate for open water disposal. Although upland placement sites are
      equipped with engineering controls (leachate collection and/or barrier walls),
      little is known of the potential impacts of this approach to air quality. The aim
      of this study was to estimate the flux of mercury to the atmosphere from New
      York/New Jersey Harbor stabilized dredged material (SDM) that was used for land
      reclamation at a site in northeastern New Jersey. Total gaseous mercury (TGM) was
      measured at a site receiving SDM in August and October 2001 and May and November
      2002. TGM was also monitored at an urban reference site 3.5 km west of the SDM
      site in September 2001 and from February 2002 to July 2002 and from October 2002
      to February 2003. The concentration of TGM at the urban reference site averaged
      2.2 +/- 1.1 ng m(-3), indicating some local contribution to the Northern
      Hemisphere background. TGM concentrations exhibited seasonality with the highest
      values in summer (3.3 +/- 2.1 ng m(-3) in June 2002) and the lowest in winter
      (1.7 +/- 0.6 ng m(-3) in January 2003). TGM concentrations at the SDM placement
      site ranged from 2 to 7 ng m(-3) and were significantly higher (p < 0.001) than
      those at the urban reference site. Sediment-air fluxes of Hg at the SDM placement
      site estimated by the micrometeorological technique ranged from -13 to 1040 ng m(
      2) h(-1) (sediment to air fluxes being positive) and were significantly
      correlated to solar radiation (r2 = 0.81). The estimated contribution of Hg
      emissions from land-applied SDM to local TGM concentrations was found to be
      negligible (<4%). However, the estimated annual volatilization rate of TGM atthe
      SDM site (130 kg y(-1))was comparable to those of other industrial sources in New
      Jersey (140-450 kg y(-1)).

PMID- 16294854
TI  - Characterization of environmental estrogens in river water using a three pronged
      approach: active and passive water sampling and the analysis of accumulated
      estrogens in the bile of caged fish.
AB  - Estrogenicity of river water is highly variable and it is difficult to obtain an
      average measure of the estrogenicity. Consequently it is difficult to tie the
      estrogenic effects observed in fish to their level of exposure to estrogens. To
      get a better handle on average estrogenic exposure we tested a recently developed
      passive sampling system (polar organic chemical integrative sampler, POCIS). In
      addition, we investigated the bioaccumulation of estrogens in caged brown trout
      and measured plasma vitellogenin in males as a bioindicator of estrogenic
      effects. We developed a mini-caging method to suit the hydrological conditions in
      small rivers and to improve upon the often poor survival of salmonids in caging
      trials. POCISs were positioned upstream and downstream of 5 sewage treatment
      works' discharges and left on site for 3 weeks (as were the caged fish), during
      which period 3 water grab samples were taken at each site. Concentrations of
      estrogens were determined using a yeast-based reporter gene assay and chemical
      analysis. Results from grab sampling, passive sampling, and bioaccumulation were
      correlated; however, plasma vitellogenin concentrations were elevated at only 1
      of 5 sites. POCISs provide an integrated and biologically meaningful measure of
      estrogenicity in thatthey accumulate estrogens in a pattern similar to that of
      brown trout. Mini-caging appears a significant methodological advance; no fish
      were lost, moreover, all fish survived in excellent health.

PMID- 16294855
TI  - Temporal development of brominated flame retardants in peregrine Falcon (Falco
      peregrinus) eggs from South Greenland (1986-2003).
AB  - A time trend between 1986 and 2003 was found for brominated flame retardants in
      peregrine falcon eggs from South Greenland, with significantly increasing
      concentrations of the polybrominated diphenyl ethers (PBDEs) 99, 100, 153, 154,
      and 209. For BDE-99 and -100, the concentration increased approximately 10% per
      year. The concentrations of PBDEs were among the highest detected in wildlife so
      far and ranged from 300 to 12,900 ng/g lipid weight (lw) for sigmaPBDE. While
      tetrabromobisphenol A (TBBPA) was below the limit of detection in all eggs,
      hexabromocyclododecane (HBCD), dimethyl-TBBPA, and brominated biphenyl BB-153
      were detected in a majority of eggs, with median concentrations of 2.4, 230, and
      550 ng/g lw, respectively. Analyses of eggs of the same bird showed no
      significant intra-clutch variation for PBDEs, BB-153, and HBCD but larger
      variations for dimethyl-TBBPA. Inter-clutch variations with increasing time
      trends exist for the BDEs 99, 100, 153, 154, and 209, while a decreasing
      contamination with the BDEs 183, 49, 47, 66 and 153 was indicated in a subset of
      eggs.

PMID- 16294856
TI  - Porewater evidence of metal (Cu, Ni, Co, Zn, Cd) mobilization in an acidic,
      ombrotrophic bog impacted by a smelter, Harjavalta, Finland and comparison with
      reference sites.
AB  - Porewaters were collected from three Finnish peat bogs subjected to varying
      inputs of atmospheric trace metals: Hietajarvi (HIJ), a low-background site,
      Outokumpu (OUT), near a Cu-Ni mine, and Harjavalta (HAR), near a Cu-Ni smelter.
      Samples for metal analyses were collected at depths ranging from 10 to 70 cm
      using a purpose-built syringe-type sampler. Metal concentrations were determined
      using inductively coupled plasma-sector field-mass spectrometry (ICP-SF-MS).
      Porewater concentrations at HIJ and OUT (Cd <0.3 nM, Co <1.4 nM, Cu, Ni <8 nM, Zn
      <250 nM) are independent of metal concentrations in the solid phase (peat). At
      OUT there is a limited release of Ni to the porewaters, but concentrations in the
      aqueous phase are generally below 0.3% of the total concentration in any given
      peat sample. These data are consistent with the immobility of these metals after
      deposition from the air. In contrast, porewaters at HAR are enriched in trace
      metals compared to the other sites by a factor of 2 (Zn), 10 (Cd), 20 (Co), and
      100 (Cu and Ni) with dissolved fractions of Cu and Ni accounting for ca. 20% of
      the metal inventories in the cores. The elevated release of metals from solid
      phases at HAR is consistent with the postdepositional migration of metals at this
      site and reflects the predominance of oxide phases supplied to the bog surface
      and the much lower pH values (<3.4). The elevated proton concentrations not only
      promote mineral dissolution but also compete with cation exchange processes and
      hinder the formation of metal complexes with organic ligands.

PMID- 16294857
TI  - Prediction of initial emission rates of 2-butoxyethanol from consumer products
      using equilibrium headspace concentrations: an application of the vapor pressure
      and boundary layer (VB) model.
AB  - The initial emission rate of volatile organic compounds (VOCs) from consumer
      products is important for assessing potential human exposure to VOCs in products.
      The vapor pressure and boundary layer (VB) model developed in the past was used
      to predict the emission rates of VOCs in the fast decaying phase from petroleum
      based wet materials. This study has extended the model to largely water-based
      products. Study results have shown a good agreement (ratio = 1.01, r2 = 0.89)
      between model-predicted initial emission rates (ER0) of 2-butoxyethanol (2-BE)
      based on its equilibrium headspace concentration and experimentally measured ER0
      in a small dynamic environmental chamber for 20 consumer products. These water
      based products included wood surface treating stains, general cleaning agents,
      and degreasers with 2-BE concentrations over a wide range. The results also
      demonstrated a dependency between the headspace concentrations of the target
      analytes and the water content in the liquid. But dependency on water content had
      no effect on the use of headspace concentration to predict the ER0. The ER0 of 2
      BE in the products ranged from 100 to 3000 mg m(-2) h(-1). In the majority of
      cases, the 2-BE concentration range in individual products indicated in the
      Material Safety Data Sheet agreed with the measured data.

PMID- 16294858
TI  - Seasonal variation in the occurrence of pharmaceuticals in effluents from a
      sewage treatment plant and in the recipient water.
AB  - The occurrence of five pharmaceuticals (ibuprofen, naproxen, ketoprofen,
      diclofenac, and bezafibrate) in the influent and effluent water of a sewage
      treatment plant (STP) in the recipient river water and in a drinking water
      treatment plant (DWTP) located downstream from the STP was followed during three
      seasons: winter, spring, and summer. In the STP, the elimination of the
      pharmaceuticals decreased significantly (an average of 25% compared to spring and
      summer) in wintertime leading to increased concentrations of pharmaceuticals in
      the effluent water. The total concentration of all the studied pharmaceuticals in
      the effluent water was 3-5 times higher in wintertime (about 2500 ng L(-1)) than
      during the other seasons (about 500-900 ng L(-1)). Accordingly, the highest
      concentrations (up to 129 ng L(-1)) in the recipient river were measured in the
      wintertime. Pharmaceuticals were carried longer distances downstream from the STP
      when the river was covered by ice and snow. During a drastic increase in water
      flow rate (i.e., during snowmelting), a fast transportation of the
      pharmaceuticals was observed. The DWTP located downstream from the STP produced
      water that contained about 8 ng L(-1) of ibuprofen and ketoprofen in the winter
      sample, whereas in spring and summer the studied pharmaceuticals could not be
      detected in the drinking water. The results show that cold seasons in boreal
      areas can severely increase the environmental risk of pharmaceuticals and the
      risk for contamination of drinking water.

PMID- 16294859
TI  - Identification of polybrominated dibenzo-p-dioxins in blue mussels (Mytilus
      edulis) from the Baltic Sea.
AB  - Polybrominated dibenzo-p-dioxins (PBDDs) are known to be formed as byproducts in
      connection with the manufacture and combustion of products containing brominated
      flame retardants. However, to date little is known about the occurrence of PBDDs
      in biological samples. The aim of the present investigation was to examine the
      presence of PBDDs in blue mussels (Mytilus edulis) from the Baltic Sea employing
      a procedure adapted for dioxin analysis. Two triBDDs (1,3,7-triBDD and 1,3,8
      triBDD) were identified in biota here for the first time. This identification was
      based on accurate mass determination and comparison of retention times on three
      gas chromatographic columns of different polarities (PTE 5, SP-2331, and
      OV1701/heptakis) with synthesized standards, together with comparisons of
      electron capture negative ionization (ECNI) and electron ionization (EI) mass
      spectra. In addition, five PBDDs and one polybrominated dibenzofuran (PBDF) were
      tentatively identified; altogether, one diBDD, three triBDDs, three tetraBDDs,
      and one triBDFwere detected in the blue mussels. To our knowledge this is the
      first time PBDDs have been identified in biota of the Baltic Sea. The sigma
      triBDD concentration in the blue mussels was estimated to be 170 ng/g lipids. The
      origin of these PBDDs remains unclear, but a plausible hypothesis could be
      biogenic formation in the marine environment.

PMID- 16294861
TI  - Compositional evolution of the emplaced fuel source in the vadose zone field
      experiment at Airbase Verlose, Denmark.
AB  - A field experiment was performed in a sandy vadose zone, studying the fate of an
      emplaced fuel-NAPL source, composed of 13 hydrocarbons and a tracer. The UNIFAC
      model was used to testthe nonideal behavior of the source, and the numerical
      model MIN3P was used for assessing the effect of biodegradation on source
      evolution. The diffusive loss to the surrounding vadose zone and the atmosphere
      created temporary gradients in mole fractions of the individual compounds within
      the source NAPL. The evolution of the source composition corresponded in general
      with expectations based on Raoult's Law, with the exception thatthe mole
      fractions of aromatic compounds in the source NAPL decreased faster than
      fractions of aliphatic compounds of similar volatility. Calculation of activity
      coefficients (y) using the UNIFAC model implied nonideal conditions, with
      composition-dependent gammas different from 1. Positive deviations were
      calculated for the aromatic compounds. The effect of biodegradation on source
      depletion, evaluated by numerical modeling, was greater for the aromatic as
      compared to the aliphatic compounds. Hence, the faster depletion of the aromatic
      relative to aliphatic compounds of similar volatility is both a result of the
      nonideality of the mixture and a result of partitioning and biodegradation in the
      pore-water. Vapor concentrations of the compounds in the source were in
      reasonable agreement with predictions based on the modified Raoult's Law with the
      UNIFAC predicted gammas and the NAPL composition for the most volatile compounds.
      For the less volatile compounds, the measured vapor concentrations were lower
      than predicted with the largest deviations for the least volatile compounds. This
      field experiment illustrated that nonideal behavior and bioenhanced source
      depletion need to be considered at multicomponent NAPL spill sites.

PMID- 16294860
TI  - Polybrominated diphenyl ethers and polychlorinated biphenyls in a marine foodweb
      of coastal Florida.
AB  - Nine species of marine fish, including teleost fishes, sharks, and stingrays, and
      two species of marine mammals (dolphins) collected from Florida coastal waters
      were analyzed for polybrominated diphenyl ethers (PBDEs) and polychlorinated
      biphenyls (PCBs) to evaluate biomagnification factors (BMF) of these contaminants
      in a coastal foodweb. In addition, bottlenose dolphins and bull sharks collected
      from the Florida coast during the 1990s and the 2000s were analyzed for
      evaluation of temporal trends in PBDE and PCB levels in coastal ecosystems. Mean
      concentrations of PBDEs in muscle tissues of teleost fishes ranged from 8.0 ng/g,
      lipid wt (in silver perch), to 88 ng/g, lipid wt (in hardhead catfish), with an
      overall mean concentration of 43 +/- 30 ng/g, lipid wt. Mean concentrations of
      PBDEs in muscle of sharks ranged from 37.8 ng/g, lipid wt, in spiny dogfish to
      1630 ng/g, lipid wt, in bull sharks. Mean concentrations of PBDEs in the blubber
      of bottlenose dolphins and striped dolphins were 1190 +/- 1580 and 660 ng/g,
      lipid wt, respectively. Tetra-BDE 47 (2,2',4,4'-) was the major congener detected
      in teleost fishes and dolphin samples, followed by BDE-99, BDE-153, BDE-100, and
      BDE-154. In contrast, BDE-209 was the most abundant congener in sharks.
      Concentrations of PBDEs and PCBs in dolphins and sharks were 1-2 orders of
      magnitude greater than those in lower trophic-level fish species, indicating
      biomagnification of both of these contaminants in the marine foodweb. Based on
      the analysis of sharks and dolphins collected over a 10-year period, an
      exponential increase in the concentrations of PBDEs and PCBs has occurred in
      these marine predators. The doubling time of PBDE and PCB concentrations was
      estimated to be 2-3 years for bull sharks and 3-4 years for bottlenose dolphin.

PMID- 16294862
TI  - Microbial reductive transformation of pentachloronitrobenzene under methanogenic
      conditions.
AB  - The reductive transformation of pentachloronitrobenzene (PCNB), an organochlorine
      fungicide, was investigated with a mixed, methanogenic culture developed from a
      contaminated estuarine sediment. Batch assays performed with this enrichment
      culture resulted in the biotransformation of PCNB to pentachloroaniline (PCA),
      which was then sequentially dechlorinated as follows: PCA --> 2,3,4,5- and
      2,3,5,6-tetrachloroaniline (TeCA) --> 2,4,5- and 2,3,5-trichloroaniline (TrCA) -
      > 2,4-, 2,5-, and 3,5-dichloroaniline (DCA) --> 3- and 4-chloroaniline (CA) (low
      levels). Glucose fermentation, methanogenesis, and dechlorination were not
      inhibited at an initial PCNB concentration up to 40 microM, which is 27 times
      higher than its aqueous solubility. The addition of 25 mM 2-bromoethanesulfonate
      (BES) to the PCNB-amended culture resulted in the complete inhibition of
      methanogenesis, but the biotransformation of PCNB to PCA and its sequential
      dechlorination pathway were not affected. The addition of sodium azide (200 mg/L)
      to the PCNB-amended culture resulted in complete inhibition of methanogenesis,
      but did not inhibit the transformation of PCNB to PCA; however, PCA
      dechlorination was not observed. PCNB was also abiotically transformed to PCA in
      autoclaved culture media but at much lower rates as compared to the biotic
      assays. In contrast, the rate of PCNB to PCA transformation in autoclaved culture
      controls was similar to the rates observed in the azide-amended culture and the
      active enrichment culture, indicating that biotically derived reductants
      facilitated the observed transformation of PCNB to PCA. Dechlorination of PCA was
      not observed in any of the abiotic controls. These findings have significant
      environmental implications in terms of the fate and transport of PCNB, PCA, and
      its dechlorination products in subsurface systems.

PMID- 16294863
TI  - Abundance, composition, and vertical transport of PAHs in marsh sediments.
AB  - Petroleum-derived hydrocarbons continue to persist in Wild Harbor, West Falmouth,
      MA, following a spill of No. 2 fuel oil in 1969 from the barge Florida. Recent
      analysis of marsh sediments revealed that residues of degraded oil are present
      with concentrations of total petroleum hydrocarbons as high as approximately 9 mg
      g(-1). Polycyclic aromatic hydrocarbons (PAHs) constitute only a minor fraction
      of these residues with maximum concentrations of 134 mirog g(-1), but their fate
      is of interest because of their potential toxicity to organisms. As compared to
      typical unweathered No. 2 fuel oil, the current distribution of PAHs in the
      sediments reflects substantial weathering by abiotic and biotic processes,
      specifically a preferential loss of naphthalenes relative to phenanthrenes, as
      well as isomer-specific biodegradation of alkylated PAHs. Based on comparison to
      results from an earlier study, it appears that little or no change has occurred
      to the distribution of PAHs since 1989, indicating that weathering at this site
      has stalled or is now proceeding at a significantly slower rate. To assess
      whether sediment-water partitioning and molecular diffusion in the interstitial
      medium are now the dominant processes controlling the vertical distribution of
      PAHs, downcore profiles were compared to a numerical model. While in some cases
      the model accurately reproduced the measured data, there were instances where the
      distribution of PAHs was slightly under or overestimated. Reasons for these
      discrepancies are discussed and are likely due to bioturbation, colloid
      facilitated transport, or both. Assessment of the influence of these processes on
      the spilled oil expands our understanding of the overall fate of these compounds
      and their potential long-term effects on the environment.

PMID- 16294865
TI  - Zinc sorption by a bacterial biofilm.
AB  - Microbial biofilms are present in soils, sediments, and natural waters. They
      contain bioorganic metal-complexing functional groups and are thought to play an
      important role in metal cycling in natural and contaminated environments. In this
      study, the metal-complexing functional groups present within a suspension of
      bacterial cell aggregates embedded in extracellular polymeric substances (EPS)
      were identified in Zn adsorption experiments conducted at pH 6.9 with the
      freshwater and soil bacterium Pseudomonas putida. The adsorption data were fit
      with the van Bemmelen-Freundlich model. The molecular speciation of Zn within the
      biofilm was examined with Zn K-edge extended X-ray absorption fine structure
      (EXAFS) spectroscopy. The Zn EXAFS data were analyzed by shell-by-shell fitting
      and linear least-squares fitting with reference spectra. Zinc sorption to the
      biofilm was attributed to predominantly Zn--phosphoryl (85 +/- 10 mol %)
      complexes, with a smaller contribution to sorption from carboxyl-type complexes
      (23 +/- 10 mol %). The results of this study spectroscopically confirm the
      importance of phosphoryl functional groups in Zn sorption by a bacterial biofilm
      at neutral pH.

PMID- 16294864
TI  - Can dawsonite permanently trap CO2?
AB  - Thermodynamic calculations indicate that although dawsonite (NaAlCO3(OH)2) is
      favored to form at the high CO2 pressures associated with carbon dioxide
      injection into sandstone reservoirs, this mineral will become unstable as CO2
      pressure decreases following injection. To assess the degree to which dawsonite
      will persist following its formation in sandstone reservoirs, its dissolution
      rates have been measured at 80 +/- 3 degrees C as a function of pH from 3 to 10.
      Measured dawsonite dissolution rates normalized to their BET surface area are
      found to be nearly independent of pH over the range of 3.5 < pH < 8.6 at 1.58 x
      10(-9) mol/(m2 x s). Use of these dissolution rates in reactive transport
      calculations indicate that dawsonite rapidly dissolves following the decrease of
      CO2 pressure out of its stability field, leading mainly to the precipitation of
      secondary kaolinite. This result indicates that dawsonite will provide a
      permanent mineral storage host only in systems that maintain high CO2 pressures,
      whereas dawsonite may be an ephemeral phase in dynamic settings and dissolve once
      high CO2 pressure dissipates either through dispersion or leakage.

PMID- 16294866
TI  - Phosphine from rocks: mechanically driven phosphate reduction?
AB  - Natural rock and mineral samples released trace amounts of phosphine during
      dissolution in mineral acid. An order of magnitude more phosphine (average 1982
      ng PH3 kg rock and maximum 6673 ng PH3/kg rock) is released from pulverized rock
      samples (basalt, gneiss, granite, clay, quartzitic pebbles, or marble). Phosphine
      was correlated to hardness and mechanical pulverization energy of the rocks. The
      yield of PH3 ranged from 0 to 0.01% of the total P content of the dissolved rock.
      Strong circumstantial evidence was gathered for reduction of phosphate in the
      rock via mechanochemical or "tribochemical" weathering at quartz and
      calcite/marble inclusions. Artificial reproduction of this mechanism by rubbing
      quartz rods coated with apatite-phosphate to the point of visible
      triboluminescence, led to detection of more than 70 000 ng/kg PH3 in the apatite.
      This reaction pathway may be considered a mechano-chemical analogue of phosphate
      reduction from lightning or electrical discharges and may contribute to phosphine
      production via tectonic forces and processing of rocks.

PMID- 16294867
TI  - Photo-fenton degradation of diclofenac: identification of main intermediates and
      degradation pathway.
AB  - In recent years, the presence of pharmaceuticals in the aquatic environment has
      been of growing interest. These new contaminants are important because many of
      them are not degraded under the typical biological treatments applied in the
      wastewater treatment plants and represent a continuous input into the
      environment. Thus, compounds such as diclofenac are present in surface waters in
      all Europe and a crucial need for more enhanced technologies that can reduce its
      presence in the environment has become evident. In this sense, advanced oxidation
      processes (AOPs) represent a good choice for the treatment of hazardous
      nonbiodegradable pollutants. This work deals with the solar photodegradation of
      diclofenac, an antiinflammatory drug, in aqueous solutions by photo-Fenton
      reaction. A pilot-scale facility using a compound parabolic collector (CPC)
      reactor was used for this study. Results obtained show rapid and complete
      oxidation of diclofenac after 60 min, and total mineralization (disappearance of
      dissolved organic carbon, DOC) after 100 min of exposure to sunlight. Although
      diclofenac precipitates during the process at low pH, its degradation takes place
      in the homogeneous phase governed by a precipitation-redissolution-degradation
      process. Establishment of the reaction pathway was made possible by a thorough
      analysis of the reaction mixture identifying the main intermediate products
      generated. Gas chromatography-mass spectrometry (GC/ MS) and liquid
      chromatography coupled with time-of-flight mass spectrometry (LC/TOF-MS) were
      used to identify 18 intermediates, in two tentative degradation routes. The main
      one was based on the initial hydroxylation of the phenylacetic acid moiety in the
      C-4 position and subsequent formation of a quinone imine derivative that was the
      starting point for further multistep degradation involving hydroxylation,
      decarboxylation, and oxidation reactions. An alternative route was based on the
      transient preservation of the biphenyl amino moiety that underwent a similar
      oxidative process of C-N bond cleavage. The proposed degradation route differs
      from those previously reported involving alternative degradation processes
      (ozonization, UV/H2O2, or photolysis), indicating that diclofenac degradation
      follows different pathways, depending on the treatment applied.

PMID- 16294868
TI  - Modeling receptor kinetics in the analysis of survival data for organophosphorus
      pesticides.
AB  - Acute ecotoxicological tests usually focus on survival at a standardized exposure
      time. However, LC50's decrease in time in a manner that depends both on the
      chemical and on the organism. DEBtox is an existing approach to analyze toxicity
      data in time, based on hazard modeling (the internal concentration increases the
      probability to die). However, certain chemicals elicit their response through
      (irreversible) interaction with a specific receptor, such as inhibition of
      acetylcholinesterase (AChE). Effects therefore do not solely depend on the actual
      internal concentration, but also on its (recent) past. In this paper, the DEBtox
      method is extended with a simple mechanistic model to deal with receptor
      interactions. We analyzed data from the literature for organophosphorus
      pesticides in guppies, fathead minnows, and springtails. Overall, the observed
      survival patterns do not clearly differ from those of chemicals with a less
      specific mode of action. However, using the receptor model, resulting parameter
      estimates are easier to interpret in terms of underlying mechanisms and reveal
      similarities between the various pesticides. We observed thatthe no-effect
      concentration estimated from the receptor model is basically identical to the
      value from standard DEBtox, illustrating the robustness of this summary
      statistic.

PMID- 16294869
TI  - Sorption and conformational characteristics of reconstituted plant cuticular
      waxes on montmorillonite.
AB  - Plant cuticular waxes are essential barriers that regulate the transport of water
      and organic molecules to intact cuticular membranes. They also compose a
      significant fraction ofthe recalcitrant aliphatic components of soil organic
      matter (SOM). In this study, we examined the sorption and desorption of three
      polycyclic aromatic hydrocarbons (PAHs), naphthalene (NAPH), phenanthrene (PHEN),
      and pyrene (PYR), by cuticular waxes of green pepper (Capsicum annuum) that had
      been reconstituted by loading them onto montmorillonite (at four different
      loadings). The reconstituted wax samples, with and without sorbed PAHs, were
      characterized by solid-state 13C NMR to supply the evidence of melting
      transition. The sorption isotherms fit well to a Freundlich equation. Sorption
      isotherms were practically linear except for that of PYR sorption to the low-load
      wax-montmorillonite sample. The organic-carbon-normalized sorption coefficients
      (Koc) depended on PAH's lipophilicity (e.g., octanol-water partition coefficient)
      and increased with increasing wax-load on clay. Desorption was dependent on PAH's
      molecular sizes and sorbed amounts and on the wax load of the clay. Desorption
      hysteresis was observed only at high loads of NAPH and PHEN, and it decreased
      with both increasing wax load and molecular size (i.e. NAPH > PHEN >> PYR).
      Contributing to hysteresis, the melting transition of the reconstituted waxes
      after sorbing the PAHs was confirmed by solid-state 13C NMR data. Upon
      adsorption, the intensity of the NMR peak at 29 ppm (attributed to mobile
      amorphous paraffinic domains) increased, and a peak at 167 ppm (-COOH) appeared,
      reflecting the transition of solid amorphous to mobile amorphous domains in the
      reconstituted waxes. The intensity of melting induced by PAH adsorption decreased
      with increasing PAH molecular size.

PMID- 16294870
TI  - Humic material induces behavioral and global transcriptional responses in the
      nematode Caenorhabditis elegans.
AB  - Humic materials are complex organic molecules constituting the most abundant
      source of natural organic matter (NOM) in freshwater and soil ecosystems. Recent
      advances have identified that they interfere with biological systems, via the
      induction of biotransformation enzymes, the inhibition of photosynthetic oxygen
      release (in freshwater plants), the production of internal oxidative stress, or
      through the feminization of fish and amphibians. The nematode model organism
      Caenorhabditis elegans was chosen to investigate whether a natural and a
      synthetic humic material induce (i) a behavioral attraction, (ii) the
      reproduction, and (iii) a response in whole genome transcriptional expression.
      The phenomenological attractant experiments provided evidence that both humic
      material sources attract the worm and exert distinct chemical cues. In the
      reproduction assay, only the highest concentration (32 mg/L DOC of Fuchskuhle
      NOM, 38 mg/L DOC of HS 1500) resulted in a decrease in brood size, highlighting
      an overall intrinsic tolerance toward humic material. Finally, oligonucleotide
      based whole genome DNA microarray experiments were performed from control and
      humic material treated worms. Significant transcriptional changes (exceeding a 2
      fold increase or decrease) were identified in chemosensors, olfactory receptors,
      as well as enzymes of the biotransformation system (cytochromes P450, UDP
      glucuronosyltransferases, glutathione S-transferases), thereby confirming that
      humic material is recognized as an environmental signaling chemical.

PMID- 16294871
TI  - Chemical extractions affect the structure and phenanthrene sorption of soil
      humin.
AB  - Humin is a major fraction of soil organic matter and strongly affects the
      sorption behavior and fate of organic contaminants in soils and sediments. This
      study evaluated four different extraction methods for soil humins in terms of
      their organic carbon structural changes and the consequent effects on
      phenanthrene sorption. Solid-state 13C NMR demonstrated that 0.1 M NaOH
      exhaustively extracted humin and humin extracted with 6 M HF/HCl at 60 degrees C
      had a relatively high amount of aliphatic components as compared with 1 M HF
      extracted humin. The treatment of 6 M HF/HCl at 60 degrees C greatly reduced
      carbohydrate components (50-108 ppm) from humin samples, i.e., more than 50%
      reduction. In addition, the humin from this 6 M HF/HCl treatment contained
      relatively more amorphous poly(methylene) domains than the humins extracted by
      other methods. With the respect to phenanthrene sorption, the linearity of
      sorption isotherm (N) and sorption affinity (Koc) varied markedly among the humin
      samples extracted by different methods. The NaOH exhaustively extracted humin had
      the most nonlinear sorption isotherm and the HF-extracted humin had the lowest
      Koc. It is concluded that humin samples from different extraction procedures
      exhibited substantial differences in their organic carbon structure and sorption
      characteristics, even though they were from the same soil. Therefore, one needs
      to be cautious when comparing the structural and sorption features of soil
      humins, especially when they are extracted differently. The 6 M HCl/HF extraction
      at elevated temperature is not encouraged, due to the modifications of chemical
      structure and physical conformation of organic matter.

PMID- 16294872
TI  - Real-world emission factors of fine and ultrafine aerosol particles for different
      traffic situations in Switzerland.
AB  - Extended field measurements of particle number (size distribution of particle
      diameters, D, in the range between 18 nm and 10 microm), surface area
      concentrations, and PM1 and PM10 mass concentrations were performed in
      Switzerland to determine traffic emissions using a comprehensive set of
      instruments. Measurements took place at roads with representative traffic
      regimes: at the kerbside of a motorway (120 km h(-1)), a highway (80-100 km h(
      1)), and in an urban area with stop-and-go traffic (0-50 km h(-1)) regulated by
      light signals. Mean diurnal variations showed that the highest pollutant
      concentrations were during the morning rush hours, especially of the number
      density in the nanoparticle size range (D <50 nm). From the differences between
      up- and downwind concentrations (or differences between kerbside and background
      concentrations for the urban site), "real-life" emission factors were derived
      using NOx concentrations to calculate dilution factors. Particle number and
      volume emission factors of different size ranges (18-50 nm, 18-100 nm, and 18-300
      nm) were derived for the total vehicle fleet and separated into a light-duty
      (LDV) and a heavy-duty vehicle (HDV) contribution. The total particle number
      emissions per vehicle were found to be about 11.7-13.5 x 10(14) particles km(-1)
      for constant speed (80-120 km h(-1) and 3.9 x 10(14) particles km(-1) for urban
      driving conditions. LDVs showed higher emission factors at constant high speed
      than under urban disturbed traffic flow. In contrast, HDVs emitted more air
      pollutants during deceleration and acceleration processes in stop-and-go traffic
      than with constant speed of about 80 km h(-1). On average, one HDV emits a 10-30
      times higher amount of particulate air pollutants (in terms of both number and
      volume) than one LDV.

PMID- 16294873
TI  - Aerosol transport in the California Central Valley observed by airborne lidar.
AB  - An aerosol lidar system was deployed on the NASA DC-8 and used to measure aerosol
      vertical profiles in the California Central Valley. The nadir-pointing Nd:YAG
      lidar operated at 532 and 1064 nm at 20 Hz. The resulting aerosol profiles were
      plotted in a unique three-dimensional format that allowed the visual observation
      of the aerosol scattering ratio profiles, the valley topography, and
      corresponding backward trajectory air masses. The accumulation of aerosols from
      the Bakersfield area can be seen in the southern end of the valley due to
      topography and prevailing winds.

PMID- 16294874
TI  - Phylogenetic analysis of TCE-dechlorinating consortia enriched on a variety of
      electron donors.
AB  - Two rapidly fermented electron donors, lactate and methanol, and two slowly
      fermented electron donors, propionate and butyrate, were selected for enrichment
      studies to evaluate the characteristics of anaerobic microbial consortia that
      reductively dechlorinate TCE to ethene. Each electron donor enrichment subculture
      demonstrated the ability to dechlorinate TCE to ethene through several serial
      transfers. Microbial community analyses based upon 16S rDNA, including terminal
      restriction fragment length polymorphism (T-RFLP) and clone library/sequencing,
      were performed to assess major changes in microbial community structure
      associated with electron donors capable of stimulating reductive dechlorination.
      Results demonstrated that five phylogenic subgroups or genera of bacteria were
      present in all consortia, including Dehalococcoides sp., low G+C Gram-positives
      (mostly Clostridium and Eubacterium sp.), Bacteroides sp., Citrobacter sp., and
      delta Proteobacteria (mostly Desulfovibrio sp.). Phylogenetic association
      indicates that only minor shifts in the microbial community structure occurred
      between the four alternate electron donor enrichments and the parent consortium.
      Inconsistent detection of Dehalococcoides spp. in clone libraries and T-RFLP of
      enrichment subcultures was resolved using quantitative polymerase chain reaction
      (Q-PCR). Q-PCR with primers specific to Dehalococcoides 16S rDNA resulted in
      positive detection of this species in all enrichments. Our results suggest that
      TCE-dechlorinating consortia can be stably maintained on a variety of electron
      donors and that quantities of Dehalococcoides cells detected with Dehalococcoides
      specific 16S rDNA primer/probe sets do not necessarily correlate well with
      solvent degradation rates.

PMID- 16294875
TI  - Sorption of aromatic organic pollutants to grasses from water.
AB  - The influence of plant lipids on the equilibrium sorption of three aromatic
      solutes from water was studied. The plant-water sorption isotherms of benzene,
      1,2-dichlorobenzene, and phenanthrene were measured over a large range of solute
      concentrations using sealed vessels containing water, dried plant material, and
      solute. The plant materials studied include the shoots of annual rye, tall
      fescue, red fescue, and spinach as well as the roots of annual rye. Seven out of
      eight sorption isotherms were linear with no evidence of competitive effects
      between the solutes. For a given plant type, the sorption coefficient increased
      with decreasing solute water solubility. For a given solute, sorption increased
      with increasing plant lipid content. The estimated lipid-water partition
      coefficients of individual solutes were found to be significantly greater than
      the corresponding octanol-water partition coefficients. This indicates that plant
      lipids are a more effective partition solvent than octanol for the studied
      aromatic compounds. As expected, the solute lipid-water partition coefficients
      were log-linearly related to the respective water solubilities. For the compounds
      studied, partitioning into the lipids is believed to be the primary sorption
      mechanism.

PMID- 16294876
TI  - Leaching of metribuzin metabolites and the associated contamination of a sandy
      Danish aquifer.
AB  - As degradation products of metribuzin have received little attention as potential
      groundwater contaminants, we evaluated leaching of metribuzin and its primary
      metabolites desaminometribuzin (DA), desaminodiketometribuzin (DADK), and
      diketometribuzin (DK) at a sandy test site in Denmark. Soil water and groundwater
      were sampled monthly over a four-year period. Leaching of metribuzin and DA was
      negligible. DK and DADK leached from the root zone (1 meter below ground surface
      (mbgs)) in average concentrations considerably exceeding the EU limit value for
      drinking water (0.1 microg/L). Both metabolites appear to be relatively stable
      and persisted in soil water and groundwater several years after application. Past
      application of metribuzin at the site had contaminated the groundwater with both
      DK and DADK, which were detected in 99% and 48%, respectively, of the groundwater
      samples analyzed. Except for three of the groundwater samples, the DADK
      concentration never exceeded the EU limit value. In contrast, the annual
      concentration of DK exceeded 0.1 microg/L at 90% of the screens analyzed. The
      present findings suggest that as the degradation products of metribuzin can leach
      through sandy soil in high concentrations, they could potentially contaminate the
      groundwater. In view of this risk DK and DADK should both be included in
      monitoring programs and their ecotoxicological effects should be further
      investigated.

PMID- 16294877
TI  - Structure-dependent reactivity of low molecular weight fulvic acid molecules
      during ozonation.
AB  - Size-exclusion chromatography coupled to quadrupole time-of-flight mass
      spectrometry (SEC-Q-TOF-MS) was used to study changes in the molecular
      composition of a Suwannee River fulvic acid isolate by ozonation. The composition
      of all three SEC fractions showed strong changes and a relative increase of the
      low molecular weight anions. Further mass spectrometric investigations focused on
      the low molecular weight fulvic acid molecules, where a preferential removal of
      fulvic acid molecules with a low oxidation state (low O/C ratio) and a high
      degree of unsaturation (low H/C ratio) was observed. Besides their elemental
      composition, also the structure of the fulvic acid molecules influenced their
      reactivity toward ozone. The data suggestthat molecules with a more extended
      carbon skeleton and less carboxylate substituents showed higher reactivitywhereas
      some highly unsaturated molecules did not show measurable removal up to a
      specific ozone dose of 2.5 mg/mg of DOC due to sterical shielding of the reactive
      structures. Newly formed molecules were determined by SEC-Q-TOF-MS, which were
      characterized by a very high number of carboxylate groups (high O/C ratio) and a
      highly saturated carbon skeleton (high H/C ratio). These investigations explain
      on a molecular level many observations previously made with whole mixtures or
      fractions of natural organic matter.

PMID- 16294878
TI  - Naphthenic acids in athabasca oil sands tailings waters are less biodegradable
      than commercial naphthenic acids.
AB  - Naphthenic acids (NAs) are natural constituents in many petroleum sources,
      including bitumen in the oil sands of Northern Alberta, Canada. Bitumen
      extraction processes produce tailings waters that cannot be discharged to the
      environment because NAs are acutely toxic to aquatic species. However, aerobic
      biodegradation reduces the toxic character of NAs. In this study, four commercial
      NAs and the NAs in two oil sands tailings waters were characterized by gas
      chromatography-mass spectrometry. These NAs were also incubated with
      microorganisms in the tailings waters under aerobic, laboratory conditions. The
      NAs in the commercial preparations had lower molecular masses than the NAs in the
      tailings waters. The commercial NAs were biodegraded within 14 days, but only
      about 25% of the NAs native to the tailings waters were removed after 40-49 days.
      These results show that low molecular mass NAs (C < or =17) are more readily
      biodegraded than high molecular mass NAs (C > or =18). Moreover, the results
      indicate that biodegradation studies using commercial NAs alone will not
      accurately reflect the potential biodegradability of NAs in the oil sands
      tailings waters.

PMID- 16294879
TI  - A statistical resampling method to calculate biomagnification factors exemplified
      with organochlorine data from herring (Clupea harengus) muscle and guillemot
      (Uria aalge) egg from the Baltic sea.
AB  - A novel method for calculating biomagnification factors is presented and
      demonstrated using contaminant concentration data from the Swedish national
      monitoring program regarding organochlorine contaminants (OCs) in herring (Clupea
      harengus) muscle and guillemot (Uria aalge) egg, sampled from 1996 to 1999 from
      the Baltic Sea. With this randomly sampled ratios (RSR) method, biomagnification
      factors (BMF(RSR)) were generated and denoted with standard deviation (SD) as a
      measure of the variation. The BMFRsR were calculated by randomly selecting one
      guillemot egg out of a total of 29 and one herring out of a total of 74, and the
      ratio was determined between the concentration of a given OC in that egg and the
      concentration of the same OC in that herring. With the resampling technique, this
      was performed 50 000 times for any given OC, and from this new distribution of
      ratios, BMF(RSR) for each OC were calculated and given as geometric mean (GM)
      with GM standard deviation (GMSD) range, arithmetic mean (AM) with AMSD range,
      and minimum (BMF(MIN)) as well as maximum (BMF(MAX)) biomagnification factors.
      The 14 analyzed OCs were p,p'DDT and its metabolites p,p'DDE and p,p'DDD,
      polychlorinated biphenyls (PCB congeners: CB28, CB52, CB101, CB118, CB138, CB153,
      and CB180), hexachlorocyclohexane isomers (alpha-, beta-, and gammaHCH), and
      hexachlorobenzene (HCB). Multivariate data analysis (MVDA) methods, including
      principal components analysis (PCA), partial least squares regression (PLS), and
      PLS discriminant analyses (PLS-DA), were first used to extract information from
      the complex biological and chemical data generated from each individual animal.
      MVDA were used to model similarities/dissimilarities regarding species (PCA, PLS
      DA), sample years (PLS), and sample location (PLS-DA) to give a deeper
      understanding of the data that the BMF modeling was based upon. Contaminants that
      biomagnify, that had BMF(RSR) significantly higher than one, were p,p'DDE, CB118,
      HCB, CB138, CB180, CB153, ,betaHCH, and CB28. The contaminants that did not
      biomagnifywere p,p'DDT, p,p'DDD, alphaHCH, CB101, and CB52. Eventual
      biomagnification for gammaHCH could not be determined. The BMF(RSR) for OCs
      present in herring muscle and guillemot egg showed a broad span with large
      variations for each contaminant. To be able to make reliable calculations of BMFs
      for different contaminants, we emphasize the importance of using data based upon
      large numbers of, as well as well-defined, individuals.

PMID- 16294880
TI  - Pore-scale characterization of organic immiscible-liquid morphology in natural
      porous media using synchrotron X-ray microtomography.
AB  - The objective of this study was to quantitatively characterize the pore-scale
      morphology of organic immiscible liquid residing within natural porous media.
      Synchrotron X-ray microtomography was used to obtain high-resolution, three
      dimensional images of solid and liquid phases in packed columns. The image data
      were processed to generate quantitative measurements of organic-liquid blob
      morphology. Three porous media, comprising a range of particle-size
      distributions, were used to evaluate the impact of porous-medium texture on blob
      morphology. The sizes and shapes of the organic-liquid blobs varied greatly,
      ranging from small spherical singlets (> or = 0.03 mm in diameter) to large,
      amorphous ganglia with mean lengths of 4-5 mm. The smaller blobs were composed
      primarily of singlets, which comprised approximately half of all blobs for all
      three media. Conversely, large, complex blobs comprising four or more bodies
      composed 11-24% of the total number of blobs. However, the majority of the total
      organic-liquid surface area and volume was associated with the largest blobs. The
      ratio of median blob size to median grain size was close to unity for all three
      systems. The distribution of blob sizes was greatest for the porous medium with
      the broadest particle-size and pore-size distributions. These results illustrate
      the utility of synchrotron X-ray microtomography for characterizing fluid
      distributions at the pore scale in natural porous media.

PMID- 16294881
TI  - Evaluation of novel techniques for measurement of air-water exchange of
      persistent bioaccumulative toxicants in Lake Superior.
AB  - We report initial measurements of concentrations and net air-water exchange
      fluxes of target persistent bioaccumulative toxicants (PBTs) in Lake Superior
      utilizing techniques not previously applied for this purpose. Gaseous PBTs are
      collected in diffusion denuders containing sections of commercial chromatography
      columns and subsequently thermally extracted into the cooled injection inlet of a
      high-resolution gas chromatograph. The PBT sampling/analytical methods enable
      accurate determination of gas-phase PBT concentration and micrometeorological
      measurement of fluxes to be carried out. PBT fluxes are measured by the modified
      Bowen ratio technique in which sensible heat flux is related to PBT flux, with
      the assumption of identical transfer velocities of heat and PBTs between two
      heights in the atmospheric surface layer. Micrometeorological measurement of flux
      accounts for all sources of resistance to mass transfer, including atmospheric
      stability effects, surface films, waves, sea spray, and bubbles. The sensible
      heatflux, PBT concentration, and PBT flux measurements carried out in 14 2- or 3
      h periods during seven sampling events in Lake Superior in summer and fall 2002
      and spring 2003 demonstrate advantages under the constraints of the techniques.
      The uncertainty of the flux measurements was typically in the range from 1% to
      160%. Gaseous concentrations of a-hexachlorocyclohexane (alpha-HCH) and
      hexachlorobenzene (HCB) over Lake Superior were in the range from 6 to 170 and 12
      95 pg/m3, respectively. Fluxes out of Lake Superior were measurable in 75% of the
      cases in which a concentration gradient was measured, and were in the range from 
      0.17 to +0.064 ng/m2 x h for alpha-HCH and from -0.60 to -0.093 ng/m2 x h for
      HCB.

PMID- 16294882
TI  - Development and application of an electron spin resonance spectrometry method for
      the determination of oxygen free radical formation by particulate matter.
AB  - Exposure to increased levels of ambient particulate matter (PM) are associated
      with several health effects, including cardiopulmonary diseases. The formation of
      reactive oxygen species (ROS) is thought to play an important role in the
      induction of these health effects. To quantify the ROS generating capacityof
      PM,we developed an improved electron spin resonance (ESR) spectrometry-based
      method. ROS formation was measured directly on PM-containing filters, thereby
      avoiding the selective extraction of components and loss of material or
      reactivity, which is likely to occur during filter extraction. Also, ascorbic
      acid was added to stimulate ROS formation. This method was applied to PM10
      samples originating from different sources. The radical generating capacity of
      PM10 from both gasoline and diesel engine exhaust was significantly higher as
      compared to that of PM10 from ambient or indoor air. Furthermore, in urban PM10
      and PM2.5, ROS-generating capacity significantly correlated with concentrations
      of polycyclic aromatic hydrocarbon content and particular transition metals. This
      indicates thatthis improved ESR method may be a valuable tool for evaluating the
      relationship between ROS formation by PM and the adverse health effects
      associated with this type of air pollution.

PMID- 16294884
TI  - Improving data quality for environmental fate models: a least-squares adjustment
      procedure for harmonizing physicochemical properties of organic compounds.
AB  - Physicochemical properties (vapor pressure, aqueous solubility, octanol
      solubility, Henry's law constant, and octanol-air and octanol-water partition
      coefficients) and their temperature dependencies are required for fate modeling
      of environmental pollutants. To be internally consistent, measured values for
      these properties often must be adjusted. The goal of adjusting the property
      values for consistency is to more accurately estimate the true values. However,
      consistency and accuracy are not synonymous. If there are systematic errors in
      one property, then adjustment for consistency may reduce the accuracy of other
      property data. Here, we provide methods for achieving consistency and improving
      accuracy in the selection of partitioning properties from literature sources.
      First, we show that a widely used procedure does not always minimize the
      adjustments of property values derived from the literature when harmonizing them
      according to thermodynamic constraints. In such cases, the final adjusted values
      (FAVs) are unnecessarily different from the literature-derived values (LDVs)
      selected from measurements. We present an improved procedure based on the theory
      of least squares that minimizes the adjustment of LDVs and allows quantitative
      propagation of uncertainty from LDVs to FAVs. When this procedure is applied to
      partitioning properties for 30 organic chemicals, FAVs obtained differ by up to
      30% from those calculated with the current adjustment procedure. Second, we point
      out that the adjustment procedure is only appropriate for correcting random
      errors in measurement data. Biased LDVs must be identified and corrected prior to
      harmonization. Using a set of 16 PCB congeners as a case study, we provide
      methods to identify biased data and discuss possible sources of bias. We present
      a new interpretation of property data for the PCBs and a new set of internally
      consistent properties and quantitative structure-property relationships that we
      recommend as the best currently available.

PMID- 16294883
TI  - Automated system for fast and accurate analysis of SF6 injected in the surface
      ocean.
AB  - This paper describes an automated sampling and analysis system for the shipboard
      measurement of dissolved sulfur hexafluoride (SF6) in surface marine environments
      into which SF6 has been deliberately released. This underway system includes a
      gas chromatograph associated with an electron capture detector, a fast and highly
      efficient SF6-extraction device, a global positioning system, and a data
      acquisition system based on Visual Basic 6.0/C 6.0. This work is distinct from
      previous studies in that it quantifies the efficiency of the SF6-extraction
      device and its carryover effect and examines the effect of surfactant on the SF6
      extraction efficiency. Measurements can be continuously performed on seawater
      samples taken from a seawater line installed onboard a research vessel. The
      system runs on an hourly cycle during which one set of four SF6 standards is
      measured and SF6 derived from the seawater stream is subsequently analyzed for
      the rest of each 1 h period. This state-of-art system was successfully used to
      trace a water mass carrying Cochlodinium polykrikoides, which causes harmful
      algal blooms (HAB) in the coastal waters of southern Korea. The successful
      application of this analysis system in tracing the HAB-infected water mass
      suggests that the SF6 detection method described in this paper will improve the
      quality of the future study of biogeochemical processes in the marine
      environment.

PMID- 16294885
TI  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with
      a matrix of carbon nanotubes for the analysis of low-mass compounds in
      environmental samples.
AB  - The use of matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF-MS) for environmental analysis has been mainlyfocused on
      qualitative analysis of high-mass molecules, such as toxins, humic acid, and
      microorganisms. Herein,we describe a novel MALDI-TOF-MS method with a matrix of
      oxidized carbon nanotubes for analysis of low-mass compounds in environmental
      samples. A number of chemicals in the environment were qualitatively analyzed by
      the present method, and it was found that most of them, especiallythe highly
      polar chemicals, were measurable with high sensitivity. With the intrinsic
      ability to measure high-mass chemicals, this method can compensate for the
      current shortage of methods for environmental analysis for the measurement of
      highly polar or high-mass chemicals. For sample analysis, arsenic speciation in
      Chinese traditional medicines was qualified and diphenylolpropane in water
      samples was quantified. With the relatively high tolerance of the method to
      interfering molecules, a simple pretreatment or even no pretreatment could be
      employed before MS detection. Furthermore, this method can be employed in a high
      throughput format.

PMID- 16294886
TI  - Application of supercritical fluid extraction (SFE) to predict bioremediation
      efficacy of long-term composting of PAH-contaminated soil.
AB  - Supercritical fluid extraction (SFE) with pure carbon dioxide was used to obtain
      desorption curves of PAHs from four contaminated industrial soils. Total PAH
      concentrations ranged from 1495 to 2439 mg/kg. The desorption curves were fitted
      with a simple two-site model to determine the rapidly released fraction (F)
      representing bioavailability of PAHs. The Fdata obtained under various SFE
      pressures were compared with degradation results of a composting method applied
      on the soils. After composting and consequent long-term maturation, the residual
      PAH contaminations ranged from 4 to 36% of the original values. A possible
      explanation of the result variations is the different bioavailability of the
      pollutants. The best correlations between degradation results and F fraction were
      obtained applying 50 degrees C and 300 bar. The F values gave very good agreement
      with degradation efficiencies and the total regression coefficients (r) ranged
      from 0.81 to 0.99. The degradation results together with bioavailable fractions
      appeared to be consistentwith organic carbon contents in the soils and with
      volatile fractions of organics. The results indicate that SFE could be a rapid
      testto predict bioremediation results of composting of PAH-contaminated soils.

PMID- 16294887
TI  - Mass-transfer limitations for nitrate removal in a uranium-contaminated aquifer.
AB  - A field test on in situ subsurface bioremediation of uranium(VI) is underway at
      the Y-12 National Security Complex in the Oak Ridge Reservation, Oak Ridge, TN.
      Nitrate has a high concentration at the site, which prevents U(VI) reduction, and
      thus must be removed. An acidic-flush strategy for nitrate removal was proposed
      to create a treatment zone with low levels of accessible nitrate. The subsurface
      at the site contains highly interconnected fractures surrounded by matrix blocks
      of low permeability and high porosity and is therefore subject to preferential
      flow and matrix diffusion. To identify the heterogeneous mass transfer
      properties, we performed a novel forced-gradient tracer test, which involved the
      addition of bromide, the displacement of nitrate, and the rebound of nitrate
      after completion of pumping. The simplest conceptualization consistent with the
      data is that the pore-space consists of a single mobile domain, as well as a fast
      and a slowly reacting immobile domain. The slowly reacting immobile domain (shale
      matrix) constitutes over 80% of the pore volume and acts as a long-term reservoir
      of nitrate. According to simulations, the nitrate stored in the slowly
      interacting immobile domain in the fast flow layer, at depths of about 12.2-13.7
      m, will be reduced by an order of magnitude over a period of about a year. By
      contrast, the mobile domain rapidly responds to flushing, and a low average
      nitrate concentration can be maintained if the nitrate is removed as soon as it
      enters the mobile domain. A field-scale experiment in which the aquifer was
      flushed with acidic solution confirmed our understanding of the system. For the
      ongoing experiments on microbial U(VI) reduction, nitrate concentrations must be
      low in the mobile domain to ensure U(VI) reducing conditions. We therefore
      conclude that the nitrate leaching out of the immobile pore space must
      continuously be removed by in situ denitrification to maintain favorable
      conditions.

PMID- 16294888
TI  - Combined removal of chlorinated ethenes and heavy metals by zerovalent iron in
      batch and continuous flow column systems.
AB  - The combined removal of chlorinated ethenes and heavy metals from a simulated
      groundwater matrix by zerovalent iron (ZVI) was investigated. In batch, Ni (5-100
      mg L(-1)) enhanced trichloroethene (TCE, 10 mg L(-1)) reduction by ZVI (100 g L(
      1)) due to catalytic hydrodechlorination by bimetallic Fe0/Ni0. Cr(VI) or Zn (5
      100 mg L(-1)) lowered TCE degradation rates by a factor of 2 to 13. Cr(VI) (100
      mg L(-1)) in combination with Zn or Ni (50-100 mg L(-1)) inhibited TCE
      degradation. Addition of 20% H2(g) in the headspace, or of Zn (50-100 mg L(-1)),
      enhanced TCE removal in the presence of Ni and Cr(VI). Sorption of Zn to ZVI
      alleviated the Cr(VI) induced inhibition of bimetallic Fe0/Ni0 apparently due to
      release of protons necessary for TCE hydrodechlorination. In continuous ZVI
      columns treating tetrachloroethene (PCE, 1-2 mg L(-1)) and TCE (10 mg L(-1)), and
      a mixture of the metals Cr(VI), Zn(II), and Ni(II) (5 mg (L-1)), the PCE removal
      efficiency decreased from 100% to 90% in columns operated without heavy metals.
      The PCE degradation efficiency remained above 99% in columns receiving heavy
      metals as long as Ni was present. The findings of this study indicate the
      feasibility and limitations of the combined treatment of mixtures of organic and
      inorganic pollutants by ZVI.

PMID- 16294889
TI  - Degradation of dye pollutants by immobilized polyoxometalate with H2O2 under
      visible-light irradiation.
AB  - A Keggin polyoxometalate (POM, i.e., PW12O40(3-)) and its lacunary derivative are
      immobilized on an anionic exchange resin through electrostatic interaction at pH
      4.6 in an aqueous dispersion. The resin-supported POM thus obtained catalyzes the
      efficient degradation of cationic dye pollutants in the presence of H2O2 under
      visible-light irradiation. To evaluate the photocatalytic system, degradation of
      a rhodamine B (RB) dye was investigated in detail using UV-visible spectroscopy,
      high performance liquid chromatography, and gas chromatography/mass spectrometry
      techniques to identify the intermediates and final products. Fluorescence
      lifetime measurements revealed the electron transfer from the visible-light
      excited RB molecules to the POMs. Electron paramagnetic resonance measurements,
      investigation of the effects of *OH and *OOH scavengers on the photoreaction
      kinetics, and IR analysis indicated that de-ethylation of RB was due to *OOH
      radicals, but the decomposition of the conjugated xanthene structure was caused
      by the peroxo species formed by interaction of H2O2 with the lacunary POM loaded
      on the resin. A total organic carbon removal of ca. 22% was achieved, and the
      recycle experiment suggested excellent stability and reusability of the
      heterogeneous catalyst. On the basis of the experimental results, a
      photocatalytic mechanism is discussed.

PMID- 16294890
TI  - Uptake of organic pollutants by silica--polycation-Immobilized micelles for
      groundwater remediation.
AB  - Interest has grown in designing new materials for groundwater treatment via
      "permeable reactive barriers". In the present case, a model siliceous surface,
      controlled pore glass (CPG), was treated with a polycation (quaternized polyvinyl
      pyridine, QPVP) which immobilizes anionic/nonionic mixed micelles, in order to
      solubilize a variety of hydrophobic pollutants. Polymer adsorption on CPG showed
      atypically slow kinetics and linear adsorption isotherms, which may be a
      consequence of the substrate porosity. The highest toluene solubilization
      efficiency was achieved for the silica-polycation-immobilized micelles (SPIM)
      with the highest polymer loading and lowest micelle binding, a result discussed
      in terms of the configuration of the bound polymer and the corresponding state of
      the bound micelles. The ability of SPIM to treat simultaneously a wide range of
      pollutants and reduce their concentration in solution by 20-90% was demonstrated.
      Optimization of SPIM systems for remediation calls for a better understanding of
      both the local environment of the bound micelles and their intrinsic affinities
      for different hydrophobic pollutants.

PMID- 16294891
TI  - Nanostructured sorbents for capture of cadmium species in combustion
      environments.
AB  - The pathways of cadmium species to form a submicrometer-sized aerosol in a
      combustion system exhaust were established. Cadmium oxide was the predominant
      species formed in the experiments and resulted in particles of a mean size of 26
      63 nm with number concentrations in the range of 2-8 x 10(6) cm(-3). Two
      different nanostructured sorbents, a solid montmorillonite (MMT) and an in situ
      generated agglomerated silica, were used for capture of the cadmium species. The
      MMT sorbent was not stable at 1000 degrees C, and structural changes resulted.
      MMT did not suppress nucleation of cadmium species and partially captured it by
      weak physisorption as established by the leachability tests. In contrast, the in
      situ generated silica nanostructured agglomerates had a high surface area,
      suppressed nucleation of cadmium species vapors, and chemisorbed them effectively
      resulting in a firm binding, as compared to the MMT sorbent. There is an optimal
      temperature-time relationship at which the capture process is expected to be most
      effective. The leaching efficiency under these conditions was less than 3.2%. The
      nanostructured silica agglomerate size can be tuned for effective capture in
      existing particle control devices.

PMID- 16294892
TI  - Polyethylenimine-modified fungal biomass as a high-capacity biosorbent for Cr(VI)
      anions: sorption capacity and uptake mechanisms.
AB  - Heavy metal pollution in the aqueous environment is a problem of global concern.
      Biosorption has been considered as a promising technology for the removal of low
      levels of toxic metals from industrial effluents and natural waters. A modified
      fungal biomass of Penicillium chrysogenum with positive surface charges was
      prepared by grafting polyethylenimine (PEI) onto the biomass surface in a two
      step reaction. The presence of PEI on the biomass surface was verified by FTIR
      and X-ray photoelectron spectroscopy (XPS) analyses. Due to the high density of
      amine groups in the long chains of PEI molecules on the surface, the modified
      biomass was found to possess positive zeta potential at pH below 10.4 as well as
      high sorption capacity for anionic Cr(VI). Using the Langmuir adsorption
      isotherm, the maximum sorption capacity for Cr(VI) at a pH range of 4.3-5.5 was
      5.37 mmol/g of biomass dry weight, the highest sorption capacity for Cr(VI)
      compared to other sorbents reported in the literature. Scanning electronic
      microscopy (SEM) provided evidence of chromium aggregates formed on the biomass
      surface. XPS results verified the presence of Cr(III) on the biomass surface in
      the pH range 2.5-10.5, suggesting that some Cr(VI) anions were reduced to Cr(III)
      during the sorption. The sorption kinetics indicated that redox reaction occurred
      on the biomass surface, and whether the converted Cr(III) ions were released to
      solution or adsorbed on the biomass depended on the solution pH. Sorption
      mechanisms including electrostatic interaction, chelation, and precipitation were
      found to be involved in the complex sorption of chromium on the PEI-modified
      biomass.

PMID- 16294893
TI  - Effect of lubricant on the formation of heavy-duty diesel exhaust nanoparticles.
AB  - The effect of lubricants on nanoparticle formation in heavy-duty diesel exhaust
      with and without a continuously regenerating diesel particulate filter (CRDPF) is
      studied. A partial flow sampling system with a particle size distribution
      measurement starting from 3 nm, approximately, is used. Tests are conducted using
      four different lubricant formulations, a very low sulfur content fuel, and four
      steady-state driving modes. A well-documented test procedure was followed for
      each test. Two different kinds of nanoparticle formation were observed, and both
      were found to be affected bythe lubricant but in differentway. Without CRDPF,
      nanoparticles were observed at low loads. No correlation between lubricant sulfur
      and these nanoparticles was found. These nanoparticles are suggested to form
      mainly from hydrocarbons. With CRDPF, installed nanoparticles were formed only at
      high load. The formation correlated positively with the lubricant (and fuel)
      sulfur level, suggesting that sulfuric compounds are the main nucleating species
      in this situation. Storage effects of CRDPF had an effect on nanoparticle
      concentration as the emissions of nanoparticles decreased over time.

PMID- 16294894
TI  - Desalination of mixed tannery effluent with membrane bioreactor and reverse
      osmosis treatment.
AB  - A limiting factor for the reuse and recycling of treated tannery wastewater for
      irrigation and other uses is the high salt content, which persists even after
      conventional treatment. Reverse osmosis (RO) membrane treatment has been shown to
      significantly reduce the salt contents of tannery effluents. However, the high
      organic content of tannery effluent leads to rapid scaling and biofouling of RO
      membranes with a consequent reduction in flux rates and performance. Membrane
      bioreactors (MBR) have been shown to be highly effective in the removal of
      organic pollutants and suspended solids from tannery effluent. This research
      investigated the use of a combined MBR and RO treatment process to treat tannery
      effluents to an acceptable level for irrigation purposes. The MBR was operated at
      17-20 h retention time, at a F/M ratio of 0.52 kg COD x kg SS(-1) x day(-1) and a
      volumetric loading rate of 3.28 kg COD x m(-3) x day(-1). This treatment reduced
      the COD, BOD, and ammonia concentrations of the effluent by 90-100%. The MBR was
      shown to be an excellent pretreatment prior to RO technology, due to the high
      removal efficiency of organic compounds and suspended solids, with average
      concentrations of 344 mg x L(-1) COD and 20 mg x L(-1) BOD achieved in the
      permeate. RO treatment reduced the salt content of the MBR permeate by up to
      97.1%. The results of the research demonstrated that the MBR system developed was
      appropriate for the treatment of tannery effluents and, in combination with the
      RO treatment, reduced the salt content to acceptable levels for irrigation. The
      MBR pretreatment reduced bio-fouling and scaling of subsequent RO treatment and
      improved the overall performance of the RO unit. It is believed that this is the
      first investigation of a combined MBR and RO treatment for tannery effluents.
      This research provided data for an outline design of a full-scale MBR and RO
      plant with a treatment capacity of 5000 m3 per day for mixed tannery effluents.

PMID- 16294895
TI  - Phenol degradation by a nonpulsed diaphragm glow discharge in an aqueous
      solution.
AB  - In the present study, a nonpulsed direct current diaphragm glow discharge process
      was developed for the first time for phenol degradation in an aqueous solution.
      The discharge was generated in a small hole in a dielectric diaphragm interposed
      between two submersed graphite electrodes. The experimental results revealed that
      supplied voltage, initial pH, iron salts, and radical scavengers impact the
      phenol degradation significantly. Enhancing the applied voltage, lowering the
      solution pH, and adding appropriate amounts of Fe2+ or Fe3+ to the solution were
      found to be favorable for phenol degradation. Carbonate ions or n-butanol in the
      solution can decelerate the phenol removal. When the treatment time is increased,
      the pH value of the solution decreased, leading to an increase in the phenol
      decomposition. It was revealed by high performance liquid chromatography and
      ionic chromatography that the main intermediates of phenol decomposition are
      hydroquinone, pyrocatechol, p-benzoquinone and organic acids. In comparison with
      the high-voltage corona discharge plasma in distilled water, this process offers
      simple technology, higher energy efficiency, easier scaleup, and easier
      applicability to salt-containing wastewater with no electrode erosion and
      electromagnetic radiation.

PMID- 16294896
TI  - Design of quinonoid-enriched humic materials with enhanced redox properties.
AB  - The primary goal of this work was to develop quinonoid-enriched humic materials
      with enhanced redox properties that could be used as potentially effective redox
      mediators and reducing agents for in situ remediation of soil and aquatic
      environments. Two different strategies were formulated and tested to derive these
      materials. The first strategy called for the oxidation of phenolic fragments
      associated with the humic aromatic core. In a second strategy, polycondensation
      of these phenolic fragments was carried out with hydroquinone and catechol. The
      oxidized derivatives and copolymers obtained were characterized using elemental
      and functional group analyses, and capillary zone electrophoresis. The redox
      properties were evaluated using ESR spectrometry and reducing capacity
      determinations. The reducing capacities of copolymers ranged between 1 and 4
      mmol/g, which were much higher than the parent material and the oxidized
      derivatives. Hence, preference should be given to the copolycondensation
      approach. The quinonoid-enriched humics are nontoxic, water soluble, and
      resistant to biodegradation; thus, they could be applied as soil amendments to
      reduce highly mobile oxoanions of heavy metals and radionuclides, or as redox
      mediators to enhance in situ bioremediation. Otherwise, cross-linked copolymers
      could be created to serve as inexpensive reductants in permeable reactive
      barriers designed to remove highly oxidized contaminants from polluted
      groundwaters.

PMID- 16294897
TI  - Degradation of drinking water disinfection byproducts by synthetic goethite and
      magnetite.
AB  - Corrosion of iron pipes leads to the release of ferrous iron, Fe(II), and the
      formation of iron oxides, such as goethite and magnetite, on the pipe surface.
      Fe(II), a potent reductant when associated with iron oxide surfaces, can mediate
      the reduction of halogenated organic compounds. Batch experiments were performed
      to investigate the kinetics and pathways of the degradation of selected
      chlorinated disinfection byproducts (OBPs) by Fe(II) in the presence of synthetic
      goethite and magnetite. Trichloronitromethane was degraded via reduction, while
      trichloroacetonitrile, 1,1,1-trichloropropanone, and trichloroacetaldyde hydrate
      were transformed via both hydrolysis and reduction. Chloroform and
      trichloroacetic acid were unreactive. Observed pseudo-first-order reductive
      dehalogenation rates were influenced by DBP chemical structure and identity of
      the reductant. Fe(II) bound to iron minerals had greater reactivity than either
      aqueous Fe(II) or structural Fe(II) present in magnetite. For DBPs of structure
      Cl3C-R, reductive dehalogenation rate constants normalized by the surface density
      of Fe(II) on both goethite and magnetite correlated with the electronegativity of
      the -R group and with one electron reduction potential. In addition to chemical
      transformation, sorption onto the iron oxide minerals was also an important loss
      process for 1,1,1-trichloropropanone.

PMID- 16294899
TI  - Comment on "New evaluation scheme for two-dimensional isotope analysis to
      decipher biodegradation processes: application to groundwater contamination by
      MTBE".

PMID- 16294898
TI  - Fractions affected and probabilistic risk assessment of Cu, Zn, Cd, and Pb in
      soils using the free ion approach.
AB  - The free ion approach quantifies the toxic effects of cationic metals on soil
      biota as a function of chemistry. The approach is here extended to calculate the
      general relationship among toxic effects as the Fraction Affected (FA), soil
      solution pH, and soil organic matter content (SOM) for Cu, Zn, Cd, and Pb within
      toxicity data sets from literature. The dependence of FA on SOM is strong, with
      the FA decreasing as the SOM increases. The dependence of FA upon pH varies; Cd
      and Zn show strong dependences while for Cu and Pb dependences are weaker. The FA
      usually decreases as the soil pH increases. When the free ion approach is
      applied, risks across soils due to different metals can be compared using the FA.
      The free ion approach may also be applied to probabilistic risk assessment. Risk
      values, using the joint probability curve approach, were derived for Pb using two
      field soil data sets. One data set, with higher SOM than that of the Pb toxicity
      data set, gave a lower risk with the free ion approach than that when the soil
      chemistry was not considered. The other data set had lower SOM than that of the
      toxicity data set and gave a higher risk with the free ion approach. Since
      literature toxicity tests are biased toward low SOM soils of circumneutral pH,
      using such data to perform classical risk assessment for soils of differing
      chemical composition can lead to misestimation of risk due to neglecting soil
      chemistry, especially in soils with extreme pH and/or SOM.

PMID- 16294900
TI  - Biological, physical factors in clinical assessment of outcome of cancer therapy.
AB  - Complex molecular and cellular biological phenomena influence the response of
      tumor and normal cell to cytotoxic agents, including irradiation. Innovative 3-D
      treatment planning and IGRT techniques allow more quantitative optmization of
      irradiation dose distribution in target volumes and OAR. More detailed reporting
      on radiation doses is required with incorporation of biological parameters in
      treatment planning and dose specification. TCP and NTCP models should be validate
      with actual clinical data. Quality assurance in radiation oncology is mandatory.
      Because of increasing concerns with health care costs, technology assessment and
      cost benefit studies should be an integral component of clinical outcome
      reporting.

PMID- 16294901
TI  - TCP and NTCP: a basic introduction.
AB  - Radiotherapy is one of the most effective treatments for cancer. The aim of
      radiotherapy is to achieve a high probability of local tumor control (tumor
      control probability, TCP) at a low risk of normal tissue complications (normal
      tissue complication probability, NTCP). This paper gives a brief introduction
      into dose response relationships for early and late radiation responses and tumor
      control. The impact of basic parameters of the fractionation schedules on these
      responses is described. Easy examples illustrate how Poisson statistics can be
      used to understand dose-response relationships in radiotherapy.

PMID- 16294903
TI  - Clinical assessment of outcome of prostate cancer (TCP, NTCP).
AB  - In the recent past there have been major advances in the management of patients
      with prostate cancer. New imaging procedures as 3-D CRT and IMRT have played a
      major role in the tretament of patients with localized prostate cancer. 3-D CRT
      allows higher doses to be delivered more precisely to the target volume with
      acceptable organs at risk morbidity. Improved tumor control results in lower
      incidence of distant metastases and better survival with an enhanced quality of
      life. This outcome yields a lower cost per treatment of patients over their life
      time.

PMID- 16294902
TI  - Tumor control probability (TCP) and normal tissue complication probability (NTCP)
      in head and neck cancer.
AB  - Clinical radiobiology is concerned with the relationship between a given
      radiation dose and the resulting biological effect on tumors and normal tissues,
      as well as with all confounding factors related to the delivery of radiation
      (e.g. dose per fraction, overall treatment time, volume of tumor/normal tissue
      irradiated, concomitant use of chemotherapy) and/or associated with preexisting
      conditions of the host (e.g. diabetes, hypertension, genetic syndromes) that may
      influence this relationship. This article briefly reviews few of the concepts
      associated with the dose-effect relationships in both normal tissues and tumors
      of the head and neck area and presents an operational way to integrate all these
      concepts into the routine radiotherapy planning processes.

PMID- 16294904
TI  - TCP and NTCP in preclinical and clinical research in Europe.
AB  - European research in radiation oncology has a long and successful tradition. The
      aim of this research is to increase the therapeutic window of radiotherapy by
      increasing the tumor control probability (TCP) and/or by decreasing the normal
      tissue complication probability (NTCP). This paper summarizes the basic
      radiobiological concept underlying treatment optimization by TCP-NTCP data and
      discusses some of the limitations of currently used models. These are
      controversial in many aspects and cannot be recommended for clinical routine
      practice but should rather be considered as a research tool.

PMID- 16294905
TI  - State-of-the-art of health care and research in Italy.
AB  - The theme of health care and research in Italy is extremely large and complex.
      The two aspects are tackled in sequence though there are elements of combination
      related to the decree law 229 of 1999. Structural, organizational and financial
      elements of the two aspects, associated problems and possible proposed solutions
      are illustrated. Hopefully, in our country the approach to health care will
      change. Health care and research should be no longer considered from the
      viewpoint of expenditure but rather as an investment and quality should be
      perceived as gain rather than as cost.

PMID- 16294906
TI  - Impact of dose and volume on radiation-induced mucositis.
AB  - There is a relationship between a given radiation dose and the resulting
      biological effect in the management of head and neck cancer. Radiation mucositis
      represents a frequent complication in cancer chemoradiation. Its prevention and
      treatment are major goals in radiation therapy schedules. Critical tissues can be
      spared using high conformal radiation therapy (3DCRT) based on consensus
      guidelines for target volume. Current approaches to radiation mucositis with
      respect to the dose and volume impact are illustrated. The monitoring system of
      late toxicity used by the authors is presented.

PMID- 16294907
TI  - Dose and volume impact on radiation-induced xerostomia.
AB  - Radiation-induced xerostomia consists in the chronic dryness of the mouth caused
      by parotid gland irradiation. Parotid glands produce approximately 60% of saliva
      while the rest is secreted by submandibular and accessory salivary glands.
      Methods of measuring the salivary output are essentially represented by 99mTc
      pertechnate scintigraphy or simpler albeit less accurate methods in stimulated or
      unstimulated saliva. There are subjective and objective criteria of
      classification and grading of the secretion of saliva. Radiation-induced
      xerostomia, namely the residual salivary gland function is evidently associated
      with the mean dose absorbed. The salivary output tends to decrease after the end
      of radiotherapy. The partial dose-volume is substantially correlated with the
      mean dose to the whole gland. As for ipsilateral irradiation for head and neck
      cancer, conformal RT or IMRT allow to spare the contralateral parotid gland
      without increasing the risk of contralateral nodal recurrences. The monitoring
      system of late toxicity used by the authors is presented.

PMID- 16294908
TI  - Impact of dose and volume on lymphedema.
AB  - Lymphedema represents one of the major problem of morbidity in breast cancer
      therapy. Approximately 15-30% of patients show more or less severe lymphedema of
      the arm, following cancer therapy. Main pathogenetic mechanisms, risk factors,
      main grading criteria and scales as LENT-SOMA, CTCv2, CTCAE v3 are presented. A
      close correlation has been documented between the extent of axillary dissection
      and the association with radiotherapy in determining an increased risk of
      lymphedema. Details of surgery and radiotherapy are relevant in the definition of
      the risk of edema of the arm. Because the axillary area does not correspond to an
      organ, evaluable parameters as V20 and Dmean available for other organs are not
      applicable. There is some evidence of a correlation between the irradiation
      volume and the development of lymphedema. Data of the impact of the dose and its
      fractionation on the development of lymphedema are contrasting. The monitoring
      system of late toxicity used by the authors is presented.

PMID- 16294909
TI  - Radiation-induced cardiovascular disease: impact of dose and volume.
AB  - The radiation-induced cardiovascular pathology represents a major cause of
      morbidity and mortality in patients undergoing therapeutic chest irradiation.
      There is a broad range of clinical manifestations probably associated with dose,
      volume and technique of irradiation. From the assumption that prevention is the
      best way to manage radiation-induced cardiotoxicity, based on the
      pathophysiogenesis of heart structures, a number of reports of the literature are
      reviewed. They consider the incidence of cardiovascular disease in patients
      affected by Hodgkin's lymphoma and breast cancer. The dosimetric prevention is
      takled in terms of therapeutic procedures and doses (IMRT, 3DCRT) with particular
      reference to the impact on cardiotoxicity of parameters as maximum heart distance
      (MHD), mean lung dose (MLD), normal tissue complication probability (NTCP) and
      V30. The different evaluation criteria of cardiotoxicity are reported, based on
      the review of the major scoring scales of acute and late complications, which
      have been worked out in the course of time (LENT-SOMA, RTOG, CTC v.2.0 and CTC
      v.3.0). The monitoring system of late toxicity used by the authors is presented.

PMID- 16294910
TI  - Impact of dose and volume on subcutaneous fibrosis.
AB  - The multifactorial genesis of radiation-induced fibrosis makes a general outline
      of the occurence of this late toxicity fairly unpredictable. Scientific knowledge
      about dose fractionation, irradiated volume, total time, conformation procedures
      including IMRT can help provide better treatments. Chemical and physical
      therapies aimed at the removal of fibrosis are still limited or under study. The
      system of monitoring late toxicity used by the authors is presented.

PMID- 16294911
TI  - Dose and volume as predictive factors of pulmonary toxicity.
AB  - Dose and volume and their correlation with the development of pulmonary toxicity
      are among the most widely studied and validated factors in radiotherapy. Most
      common treatment planning systems allow prompt assessment of Vdose and Mean Lung
      Dose (MLD). The former represents the percentage of normal lung parenchyma
      receiving a dose equal to or higher than the established threshold dose; the
      latter corresponds to the mean dose delivered to the normal lung parenchyma. Most
      important studies reported on the subject and threhold values recommended for
      Vdose and MLD are analyzed. The monitoring system of late toxicity used by the
      authors is presented.

PMID- 16294912
TI  - Impact of dose and volume on rectal tolerance.
AB  - Based on the successful results achieved in survival and local control with
      radiotherapy of prostate cancer recent studies tried to establish some models to
      reliably predict late rectal toxicity. In fact, the rectum, due to its location,
      represents an organ at risk of acute and late toxicity with the onset of acute or
      chronic radiation proctitis. The concept of late consequential effect has gained
      ground. It implies that the late damage might be a direct consequence of the
      acute damage. Dose-escalation studies, conformal radiotherapy (3D-CRT) and
      intensity modulated radiotherapy (IMRT) led to the identification of parameters,
      based on dose-volume histograms (DVH), able to separate patients at low and high
      risk of toxicity. Precise predictive dosimetric factors play a major role in the
      definition of the onset of toxicity. The monitoring system of late toxicity used
      by the authors is presented.

PMID- 16294913
TI  - Impact of dose and volume on the tolerance of central nervous system.
AB  - Radiotherapy still plays a major role in the treatment of brain lesions. Its end
      points are not only better survival but especially better disease control that
      positively impacts on better quality of life. However radiotherapy is not free of
      both acute and late side-effects. Data on late toxicity are disappointing, for
      inadequate follow-up time and the absence of cards for collecting information
      shared by the scientific community in an attempt to acheive a common, universal
      language. While these treatments should be considered for palliation, the main
      goal is always the patient with his/her quality of life, and their toxicity
      should be monitored to optimize therapeutic outcomes and lower the incidence of
      complications. The monitoring system of late toxicity used by the authors is
      presented.

PMID- 16294914
TI  - Radiotherapy-related fatigue: incidence and predictive factors.
AB  - Radiotherapy-induced fatigue is a common early and chronic side-effect of
      irradiation, reported in up to 80% and 30% of patients respectively during
      radiation therapy and at follow-up visits. The factors that cause fatigue and the
      exact mechanisms responsible for its production, sustenance, or amelioration are
      not well understood. Multiple correlates and mechanisms have been proposed in the
      literature and integrated within models of cancer-related fatigue. A
      multidimensional approach in clinical practice is proposed based on the
      evaluation of cancer-related fatigue, and on the development of an adequate
      management. The monitoring system of fatigue used by the authors is presented.

PMID- 16294915
TI  - A review of hazardous chemical toxicity studies utilizing genetically-modified
      animals--their applications for risk assessment.
AB  - Studies on the mechanisms of chemical toxicity carried out using knockout mice
      lacking genes of enzymes for drug metabolism or nuclear receptor proteins were
      reviewed, and the studies were compared with the respective conventional
      mechanistic studies. While the toxicity of many hazardous chemicals was observed
      only in wild-type or knockout mice, which clearly showed that their toxicity was
      involved in the enzyme or receptor, some chemicals exhibited the same degree of
      toxicity in two genotypes, i.e., in both the wild strain and knockout mice,
      demonstrating that the enzymes or receptors are not involved in their toxicity.
      The use of genetically-modified animals presents not only the advantage of
      simultaneous evaluation of toxicity endpoints and mechanisms, but also suggests
      significant benefits over conventional methods using several chemicals to
      elucidate toxicity mechanisms. Elucidation of the mechanism of toxicity will
      provide useful information for risk assessment, and the use of genetically
      modified animals for this purpose will lead to the advancement of this
      assessment.

PMID- 16294916
TI  - Influence of overtime work, sleep duration, and perceived job characteristics on
      the physical and mental status of software engineers.
AB  - To investigate the impact of overtime work, sleep duration, and perceived job
      characteristics on physical and mental status, a cross-sectional study was
      conducted on 377 workers (average age; 28 years old) in an information-technology
      (IT) company, engaged in consultation, system integration solution, and data
      management relevant to IT system. The psychophysical outcomes of overtime work
      were assessed using the Hamilton Depression Scale (HDS), Profile of Mood Status
      (POMS), major physical symptoms, and overtime work data for the preceding three
      months. Sleep duration was directly asked by a physician. A job strain index was
      defined as the ratio of job-demands to job-control scores evaluated using the Job
      Content Questionnaire (JCQ). In a univariate analysis, overtime work was
      significantly related with HDS scores, POMS anger-hostility scores, and the total
      physical symptom count in both sexes (all p < 0.05), but not in multiple
      regression models, after controlling for sleep duration and the job strain index.
      Sleep duration was negatively related to the symptom count in men and to POMS
      tension-anxiety scores in women (both p < 0.05); the job strain index was
      positively related to POMS anger-hostility scores in both sexes and to HDS scores
      and POMS tension-anxiety scores in men (all p < 0.05). Although overtime work was
      associated with physical and mental complaints, sleep duration and the job strain
      index seemed to be better indicators for physical and mental distress in
      overloaded workers.

PMID- 16294917
TI  - Neuro-physiological study in persons with cervico-brachial disorders.
AB  - OBJECTIVES: In order to clarify the involvement in the nervous system by cervico
      brachial disorders (CBD), we performed neurophysiological tests on the peripheral
      nervous system (PNS) and the central nervous system (CNS) in patients with CBD,
      subclinicals and healthy controls. SUBJECTS AND METHODS: We employed antidromic
      sensory nerve conduction velocities (SCV) in the hands and fingers for PNS
      function and event-related potentials (P300) for CNS higher function. Subjects
      for SCV were 27 patients, 14 workers with sign and symptoms of CBD (subclinicals)
      and 22 controls. Subjects for P300 were 23 patients, 12 subclinicals and 10
      healthy controls. CONCLUSIONS: In the PNS, since significant reduction SCV in the
      index finger among patients was observed, we could not find clear evidence of
      decrease of conduction function. In the CNS, since the latencies and amplitudes
      of auditory P300 among patients were significantly delayed and decreased,
      respectively, and the latencies significantly correlated with symptom score, it
      was suggested that the dysfunction of the cognition and memory function. However,
      further investigation is necessary to clarify the mechanism.

PMID- 16294918
TI  - Risk factors for musculoskeletal symptoms among call center operators of a bank
      in Sao Paulo, Brazil.
AB  - OBJECTIVE: Identify risk factors for musculoskeletal symptoms among call center
      operators of a bank in Sao Paulo, Brazil. METHODS: Ergonomic work analysis was
      carried out, involving work observation and interviews. Self-answered
      questionnaires performed by 108 call center operators. RESULTS: Women represented
      88% of the call center operators, 70% of them were in the age bracket of 18 to 23
      yr. Daily working time was 6-h with one 30 min break. Workers remained seated 95%
      of the time, typing and answering telephone calls. Men' s work consisted of more
      active telemarketing and women's of customer services. Among female operators the
      prevalence of neck/shoulder symptoms was 43% (95% CI, 33-53) and of wrist/hand
      was 39% (95% CI, 29-49). Risk factors associated with wrist/hand symptoms were:
      inadequate height of table (Odds ratio (OR) 3.67, 95% CI, 1.12-11.96) and to
      answer above 140 calls/d (OR 3.36, 95% CI, 1.16-9.71). Risk factors associated
      with neck/shoulder symptoms were making fewer rest breaks (OR 3.17, 95% CI, 1.11
      8.97) and inadequate thermal comfort (OR 3.06, 95% CI, 1.09-8.62). CONCLUSIONS:
      Prevention of musculoskeletal disorders among call center operators requires an
      integrated approach including improved workstation design, thermal comfort
      environment, well-scheduled work-rest regime and realistic production goals.

PMID- 16294919
TI  - Comparison of disability duration of lumbar intervertebral disc disorders among
      types of insurance in Korea.
AB  - The incidence of work-related musculoskeletal disorder including low back pain
      sharply increased since 2000 in Korea. The objectives of the present study are to
      compare disability duration of lumbar intervertebral disc displacement among
      types of insurances, and to obtain its appropriate duration. The medical records
      of all patients whose final diagnosis in discharge summary of chart was lumber
      specified intervertebral disc displacement (LIVD) in 6 large general hospitals in
      Korea were reviewed to compare the length of admission and disability among
      different types of insurances. The information on age, gender, the length of
      admission, the length of follow-up for LIVD, occupation, operation, combined
      musculoskeletal diseases, and type of insurance was investigated. 552 cases were
      selected and analyzed to calculate arithmetic mean, median, mode, and geometric
      mean of disability duration. There was a significant difference in the length of
      admission and disability among types of insurance after controlling covariates
      such as age and combined diseases by the analysis of covariance. The length of
      admission in cases of IACI and AI was much longer than that of HI, and the length
      of disability in cases of IACI was much longer than that of HI. Prolonged
      duration of admission and disability was not assumed due to combined diseases,
      complication or other unexplainable personal factors in cases of those with
      industrial accidents compensation insurance and automobile insurance. This means
      that proper management of evidence-based disability duration guidelines is
      urgently needed in Korea.

PMID- 16294920
TI  - Exposure to vehicular pollution and respiratory impairment of traffic policemen
      in Jalgaon City, India.
AB  - The ambient air quality monitoring was carried during the May 2003 to April 2004
      along the (NH-6) passing through Jalgaon city. The average concentration of SOx
      64 microg/m3, NOx 58 microg/ m3, particulates (> 10 micro) 515 microg/m3 and
      respirable dust particulates 224 microg/m3 was reported at Prabhat during the
      study period (May 2003-April 2004). This location represents the major highway
      crossings (four) in the study area. The present investigations are on the survey
      of health status and lung function of traffic policemen exposed to the inferior
      air quality as observed on the highway crossings. The spirometric analysis of
      traffic policemen shows significant variation in Peak Expiratory Flow Rate
      (PEFR), Forced Expiratory Volume in one second (FEV1) and Forced Vital Capacity
      (FVC). The parameters were significantly affected in the traffic policemen as
      against the control group of population. It reveals significant respiratory
      impairment in the traffic policemen due to exposure to vehicular pollution. The
      study suggest the compulsory use of personal protective equipment (nose mask) by
      the traffic policemen during duty hours will help for the protection from
      vehicular pollution. The regular periodic health checkup is required to
      understand the impact of vehicular pollution on the health of traffic policemen.

PMID- 16294921
TI  - Early biochemical alterations in manganese toxicity: ameliorating effects of
      magnesium nitrate and vitamins.
AB  - Manganese-induced early biochemical changes and effects of supplementation of
      magnesium nitrate (Mg(NO3)2) and antioxidant vitamins (A, C, D and E) were
      studied in rats intoxicated with manganese. Significant elevation in the level of
      chlorides in plasma, erythrocytes, liver and cerebellum, and a decrease in plasma
      inorganic phosphate (pi) with an increase in liver pi were observed in animals
      exposed to manganese as compared to controls. The level of erythrocyte-acid
      labile phosphate (ALP), nicotinamide adeninedinucleotide (NAD+) and plasma sialic
      acid (N-acetylneuraminic acid, NANA) also increased significantly. Elevated
      levels of chlorides in plasma, erythrocytes and cerebellum reversed to normal
      control values whereas liver chlorides restored partially by the supplementation
      of Mg(NO3)2. Vitamins supplementation was effective to reverse chlorides level in
      erythrocytes, liver and cerebellum. Decreased level of pi in plasma and the
      highly elevated level of erythrocyte ALP were also recovered in animals received
      Mg(NO3)2 in addition to MnSO4. However, such effect of Mg(NO3)2 was not seen in
      lowering the elevated level of NANA that restored by the administration of
      vitamins. Thus, the early alterations in plasma levels of chlorides, pi, and NANA
      and erythrocyte-ALP seem to be an indicative of early manganese toxicity while
      Mg(NO3)2 and vitamins supplementation appear to provide, at least in part,
      protection against manganese toxicity.

PMID- 16294922
TI  - Model development for health promotion and control of agricultural occupational
      health hazards and accidents in Pathumthani, Thailand.
AB  - In Thailand, agriculture is one of the major occupations; however, there is no
      comprehensive agricultural occupational health promotion and disease prevention
      model available. Objectives of this study were to empower farmers to study
      occupational health and safety situation in rice farming and to develop model to
      promote their health and prevent occupational health hazards among them. This
      participatory action research was performed in Tambol Klong 7, Klongluang
      district, Pathumthani, Thailand. The 24 rice farmers from 9 villages were
      voluntarily recruited as members of research team called farmer-leader research
      group. This group had a monthly meeting to discuss issues of agricultural
      occupational health and safety during 3 yr study period. At first stage, farmer
      leader research group analyzed occupational health and safety during rice farming
      process. After we had results from situation analysis, farmer-leader research
      group decided which problems would be solved first. We developed model to solve
      those problems during the second stage. Finally, model was implemented to farmers
      in the study area. During first stage, results of questionnaires showed that
      there were 3 major occupational health and safety problems among these farmers;
      symptoms from pesticide exposure (65% of respondents), musculoskeletal problems
      during various process (16.6%-75.9%), and injuries during various process (1.1%
      83.2%). From these results, farmer-leader research group decided to deal with
      pesticide problem. There was an experiment comparing using biofertilizers and bio
      pest-control with using chemical fertilizers and pesticides in the rice paddy.
      Results showed that the biological field produced the same amount of rice as the
      chemical field but cost less money than the chemical one. Benefits from using
      biofertilizers and bio pest-control were having higher profit, less exposure to
      chemicals, and good mental health from higher profit. After this experiment,
      biofertilizers and bio pest-control were disseminated to rice-farmers and
      students and teachers in local schools. At the end of study, we found that there
      were networks of farmers and networks of students-teachers using biological
      methods. This study showed that participation with farmers could create a real
      sustainable model to promote farmers' health and prevent them from occupational
      health hazards.

PMID- 16294923
TI  - Undergraduate training in occupational health at Kocaeli University Medical
      School: a Turkish experience.
AB  - Processes and conditions of production may produce unhealthy effects. Both must
      therefore be included in the education of health care personnel. Vocational
      training in occupational health at Kocaeli University Medical School, Turkey aims
      to demonstrate students that occupational health is a specific and important area
      of work within the context of primary health care. This research is a cross
      sectional study. It was planned as a three stage study: 1- reviewing literature
      and grouping of countries according to their occupational health curricula; 2-
      reviewing the occupational health programs of medical schools in Turkey, and 3-
      recommendations for an occupational health curriculum to include an occupational
      health vocational training period of one week in the two month public health
      education program for medical interns. During this experience, senior students
      would be assigned to workplace health units. Of 283 medical schools found on the
      web, with occupational health teaching, only 20 have a curriculum that includes
      training in workplace health care units. In Turkey, there is no structured
      practical education on occupational health. In the third part of this study, we
      initiated at Kocaeli University School of Medicine's curriculum, a new
      occupational health education model applied in the workplace health units of
      factories. Practical experience of occupational health in the workplace is useful
      in introducing the community-based approach to occupational health in
      undergraduate medical education and understanding the determinants of health in
      industry.

PMID- 16294924
TI  - Effects of in utero and lactational exposure to bisphenol A on thyroid status in
      F1 rat offspring.
AB  - Bisphenol A (BPA), a xenoestrogen, has been reported to mimic the actions of
      estrogen or to affect the endocrine glands in vivo and in vitro. In this study,
      we examined whether in utero and lactational exposure to BPA alters thyroid
      status in rat F1 offspring. Dams were orally administered various doses of BPA
      (0, 4 or 40 mg/kg body weight per day) from gestation day (GD) 6 through
      postnatal day (PND) 20. The BPA and control groups did not differ significantly
      with respect to plasma thyroxine (T4) concentration. The thyroid glands from the
      BPA groups had normal T4 responses to exogenous thyroid-stimulating hormone in
      vivo. These results suggest that in utero and lactational exposure (indirect
      exposure) to BPA (4-40 mg/kg/day, GD 6 - PND 20) does not affect thyroid
      functions in the F1 generation of male and female rats.

PMID- 16294925
TI  - Comparison of colorimetric and HPLC methods for determination of delta
      aminolevulinic acid in urine with reference to dose-response relationship in
      occupational exposure to lead.
AB  - Both traditional colorimetry and recently developed HPLC-fluorometry have been in
      use for determination of delta-aminolevulinic acid in urine (ALA-U), an effect
      marker of occupational exposure to lead (Pb). The present study was initiated to
      compare the values by the two methods on an epidemiology basis among workers
      occupationally exposed to lead (Pb), to estimate quantitatively the colorimetry
      associated increment over the values by the HPLC method, to evaluate ALA-U
      determination in occupational health service for Pb-exposed workers, and to
      identify a critical Pb-B to induce an elevation in ALA-U. For this purpose, blood
      and urine samples were collected from three groups of Pb-exposed workers (both
      men and women in combination, including smokers) and analyzed for Pb in blood (Pb
      B; measured in all subjects) and ALA-U (by colorimetry or HPLC), i.e., Group 1
      (164 subjects with urinalysis by the two methods), Group 2 (2,923 subjects by
      colorimetry), and Group 3 (2,540 subjects by HPLC). ALA-U when measured by
      colorimetry was higher than the values by HPLC, and that the mean difference on a
      group basis was 1.4 mg/l (in a range of 1.1 to 1.8 mg/l), irrespective of Pb-B
      levels. It was also found that the increase in ALA-U was small when Pb-B was
      relatively low (e.g., < or = 40 microg/100 ml), and that the increase on a group
      basis in response to an increase in Pb-B from 5 to 40 microg/100 ml was as small
      as < or = 0.6 mg/l. Thus, ALA-U appeared to be not a sensitive marker of Pb
      effects at low Pb-B levels. ALA-U however increased substantially with a point of
      inflection at the Pb-B level of about 17-34 microg/100 ml. Thus it was concluded
      that ALA-U as measured by colorimetry is greater than ALA-U by HPLC by 1.4 mg/l
      on average irrespective of intensity of Pb-exposure, which may induce bias in
      evaluation of health effect, and that ALA-U levels will increase when Pb-B is in
      excess of 17-34 microg/100 ml.

PMID- 16294926
TI  - 4-oxo-2-hexenal, a mutagen formed by omega-3 fat peroxidation, causes DNA adduct
      formation in mouse organs.
AB  - To identify mutagens formed in a model reaction of lipid peroxidation, linolenic
      acid methyl ester and hemin were reacted with dG. As a result, a 4-oxo-2-hexenal
      dG adduct (dG*) was identified in the model reaction mixture. The 4-oxo-2-hexenal
      (4-OHE) showed mutagenic activity in the Salmonella typhimurium strains TA100 and
      TA104. After 4-OHE was orally administered to mice, dG, 4-OHE-dC- and 4-OHE-5
      methyl-dC adducts were detected in esophageal, stomach and intestinal DNA. In the
      vapor phase released from the methyl linolenate-hemin model system, and in the
      smoke released during the broiling of fish, 4-OHE was detected by GCMS. The 4-OHE
      seems to be produced by the auto-oxidation of omega-3 polyunsaturated fatty
      acids. These results provide a warning to workers dealing with omega-3 fats, who
      may be exposed to this volatile mutagen.

PMID- 16294927
TI  - Formaldehyde exposure in some educational hospitals of Tehran.
AB  - This research was conducted to determine formaldehyde exposure of staffs in
      pathology laboratories, surgery rooms and endoscopy wards in eight large
      hospitals of Tehran University of Medical Sciences located at Tehran, Iran. Air
      sampling have been made by both long and short-term methods. Total numbers of
      samples were 160 for both methods. Nineteen samples of 160 samples were collected
      as blank in other non-exposed environments such as administrative sections. The
      mean (SD) levels of formaldehyde in long-term methods were 0.96 (0.74), 0.25
      (0.21) and 0.13 (0.18) ppm, at pathology laboratories, surgery rooms and
      endoscopy wards, respectively. The results of measurements showed that mean (SD)
      concentration of formaldehyde in one hour sampling at short intervals were 0.83
      (0.29), 0.23 (0.16) and 0.75 (0.25) ppm at pathology labs, surgery rooms and
      endoscopy wards, respectively. There were significant differences in the mean
      levels of formaldehyde (long-term) at surgery rooms (p < 0.02) and endoscopy
      wards (p < 0.005) in eight hospitals of this study. It is concluded that the
      concentration levels of formaldehyde at pathology laboratories exceeded
      recommended limit which established by the American Conference of Governmental
      and Industrial Hygienists ACGIH (TLV-C = 0.3 ppm). It is recommended that local
      exhaust ventilation should be installed to minimize the contact to formaldehyde
      in the staffs.

PMID- 16294928
TI  - Korean initiative of GHS activities.
AB  - To implement a globally harmonized system of classification and labelling of
      chemicals (GHS) in Korea, an interminsterial GHS committee involving 6 ministries
      established an expert working group composed of 7 experts from relevant
      organizations and one private consultant to prepare an official Korean GHS
      version by March, 2005. As such, the translation and review of the official
      Korean GHS version, including annexes, started in October, 2004 and was completed
      on March 15, 2005. The official Korean GHS version has now been posted on the
      websites of the relevant ministries and organizations to solicit public opinions.
      The official Korean GHS version will be finalized after a public hearing
      scheduled for May, 2005. Collaborative efforts as regards implementing and
      disseminating the GHS in Korea will be continued to avoid any confusion or
      duplication and for effective use of resources.

PMID- 16294929
TI  - Choosing our future leaders.

PMID- 16294930
TI  - Conscious sedation and special needs patients.

PMID- 16294931
TI  - Oral manifestations of a child with chronic vomiting.
AB  - Perimolysis is a type of intrinsic erosion--an irreversible dental
      demineralization linked to chronic regurgitation--which causes teeth to be more
      susceptible to dental caries. The purpose of this case report was to study a 35
      month-old chronic vomiting child who visited the Department of Pediatric
      Dentistry in Yonsei Dental Hospital, Seoul, South Korea, for an evaluation of and
      treatment for the loss of tooth structure of his primary teeth. To prevent
      further destruction of the teeth and maintain occlusal height, all the posterior
      teeth were restored with stainless steel crowns and all the anterior teeth were
      restored with resin veneer crowns after pulpal treatment under general
      anesthesia. Therefore, when a child suffering from chronic vomiting visits a
      pediatric dental clinic, it is prudent to: (1) perform all possible dental
      treatment to control vomiting's adverse influences on the oral structures; and
      (2) refer the patient to a pediatrician to determine the cause of vomiting.

PMID- 16294932
TI  - Palatal erythema in patients using Listerine Cool Mint PocketPaks Oral Care
      Strips: case reports.
AB  - The purpose of this report was to present 2 cases of similar erythematous lesions
      in patients using Listerine Cool Mint PocketPaks Oral Care Strips. The first
      case, a 44-year-old female presented with an erythematous, well-defined, macular
      lesion centrally located on the midhard palatal gingiva. The second case involved
      a healthy 7-year-old Hispanic female who presented with a similar lesion and the
      same clinical presentation. Both presented as solitary lesions involving the
      height of the palate, with bilateral congruency to the mid-palatal suture line.
      The lesions were square in shape, with 3 sides being distinctly demarcated. The
      fourth side feathered anteriorly, gradually disappearing as it approached the
      anterior third of the palate. On verbal questioning in both cases, no discomfort
      or irritation was indicated in the medical history or by the patient. Both
      patients indicated regular use of Listerine Cool Mint PocketPaks Oral Care
      Strips. Treatment consisted of a: (1) recommendation that the strips be
      discontinued; and (2) re-evaluation of the lesions at the follow-up appointments
      to make assessments for any possible changes in lesion color, size, or shape.
      Following discontinuance of the Oral Care Strips, the lesions disappeared. Follow
      up appointments suggest an allergic contact focal erythema caused by prolonged
      contact with the irritant, in this case due to use of Listerine Cool Mint
      PocketPaks Oral Care Strips.

PMID- 16294933
TI  - The mandibular lingula's position in children as a reference to inferior alveolar
      nerve block.
AB  - PURPOSE: The objective of this study was to evaluate the position of the
      mandibular lingula (ML) to provide data for inferior alveolar nerve block
      techniques in children. METHODS: One hundred fifty-four panoramic radiographs of
      7- to 10-year-old boys and girls were analyzed. Measurements were taken from the
      ML to the occlusal plane, and the percentile distances of the ML to ramal borders
      were determined. RESULTS: The distance between the ML and the occlusal plane
      showed a gradual increase, but only in the male group was it statistically
      significant. ML's ratio position on the ramus remained constant in all analyzed
      groups. In the 7-year-old group, the ML was observed above the occlusal plane in
      70% of girls and 55% of boys. That percentage reached 85% of all children by age
      10. CONCLUSIONS: The mandibular lingula's ratio position remained constant.
      Inferior alveolar anesthesia should be administered at least 6 mm above the
      occlusal plane in 7- to 8-year-old children, while 10 mm could be indicated for 9
      to 10-year-old children. The mandibular lingula should be considered a reliable
      reference for further studies of inferior alveolar nerve block techniques.

PMID- 16294934
TI  - Rural Puerto Rican women's views on children's oral health: a qualitative
      community-based study.
AB  - PURPOSE: The purpose of this study was to examine women's views on beliefs,
      preferences, and behaviors relevant to children's oral health. METHODS: Women of
      childbearing age and mothers of women of childbearing age were recruited from 2
      rural Puerto Rican communities to participate in 24 focus groups. One hundred
      fifty women participated. Participants were asked about their awareness and
      knowledge of childhood decay and their child-feeding and oral care attitudes and
      practices. Analysis consisted of a comprehensive content review of participant's
      responses. RESULTS: Participants used a variety of infant and toddler feeding
      practices, including breastfeeding and prolonged bottle use. Children progressed
      through feeding stages based on mother's experience, older relatives' advice, and
      child readiness. Grandmothers were considered trusted and reliable sources of
      information. Many believed that dental disease did not affect infants and were
      unaware of el sindrome del biberon (baby bottle tooth decay, SIB). Participants
      believed that decay was caused by too much sugar and prolonged bottle use and
      only affected children. Dental visits were rare in very young children, unless
      conspicuous decay or pain was present. Mothers' dental experiences influenced
      seeking children's preventive and treatment visits. CONCLUSIONS: This study
      highlights caregivers' perceptions, which are inconsistent with maximizing
      children's oral health. This information can be used to develop culturally
      appropriate, community based oral health programs.

PMID- 16294936
TI  - Parental acceptance of behavior management techniques for children with clefts.
AB  - PURPOSE: The purpose of the present study was to assess the acceptance of 4
      techniques employed for child behavior management during dental treatment.
      METHODS: Four hundred caretakers of 4- to 10-year-old children with cleft lip
      and/or palate presented for dental treatment at the Hospital for Rehabilitation
      of Craniofacial Anomalies, University of Sao Paulo, Bauru, Sao Paulo, Brazil.
      They were interviewed after explanation and presentation of photographs
      illustrating the sequence of the following techniques: tellshow-do; voice
      control; physical restraint; and hand-over-mouth. RESULTS: The levels of
      acceptance of the techniques were 98%, 96%, 81%, and 85%, respectively. A large
      acceptance was observed for all techniques investigated. The caretakers' fear
      that the techniques might make the child afraid of the dentist was commonly
      mentioned as nonacceptance for all techniques. CONCLUSIONS: It was concluded that
      it is important for pediatric dentistry professionals to inform parents about
      each technique's objectives before application to avoid possible
      misunderstandings and to foster a trusting relationship between the child, the
      parents, and the dentist.

PMID- 16294935
TI  - Prevalence of bruxism and associated correlates in children as reported by
      parents.
AB  - PURPOSE: The purpose of this study was to determine the prevalence of childhood
      bruxism and associated correlates, as reported by parents. METHODS: A cross
      sectional survey of parents was conducted at 4 private pediatric dental offices
      and the Children's Hospital Boston Dental Clinic. Data were gathered via a self
      administered questionnaire offered to the parents of children under age 17.
      Factors were evaluated for association with bruxism using chi-square tests and
      multivariate logistic regression. RESULTS: Based on 854 surveys analyzed, the
      children's mean age was 8.1 years and 52% were female. Caucasians represented 87%
      of the population, and 90% of the parents had attained a high school diploma. The
      overall prevalence of reported bruxism was 38%. Five percent of the parents
      reported that their children had subjective symptoms of temporomandibular
      disorder (TMD); however, these were not associated with reported bruxism. A child
      with a psychological disorder had a 3.6 times greater likelihood of bruxism. If
      either parent had a history of bruxism, their child was 1.8 times more likely to
      brux. If bedroom doors were open, parents reported bruxism 1.7 times more often.
      Children who drooled at night were 1.7 times more likely to brux, while
      sleeptalking children were 1.6 times more likely to brux. CONCLUSIONS: (1) Of the
      38% of parents reporting that their children brux, familial history, open bedroom
      doors, drooling, sleeptalking, and psychological disorders were significantly
      associated with the reported bruxism. (2) While 5% of parents reported that their
      children had at least one TMD symptom, no TMD symptoms were associated with
      reported bruxism.

PMID- 16294937
TI  - Factors associated with comprehensive dental care following an initial emergency
      dental visit.
AB  - PURPOSE: The purpose of this study was to characterize the patient population
      utilization of a dental home as grouped by: (1) age; (2) sex; and (3) payment
      method. METHODS: A retrospective chart review of 1,020 patients, who initially
      presented for an emergency visit, was performed. From the original data pool, 2
      groups were delineated: (1) those patients who returned for comprehensive dental
      care; and (2) those who did not return for comprehensive dental care. RESULTS:
      Patients with private dental insurance or Medicaid dental benefits were
      statistically more likely to return for comprehensive oral health care than those
      with no form of dental insurance. Younger patients (< or =3 years of age) were
      least likely to return for comprehensive dental care. CONCLUSIONS: Socioeconomic
      factors play a crucial role in care-seeking behaviors. These obstacles are often
      a barrier to preventive and comprehensive oral health care.

PMID- 16294938
TI  - Primary dentition unilateral crossbite in relation to functional lateralities.
AB  - PURPOSE: The aim of this study was to explore primary dentition unilateral
      crossbite malocclusion prevalences in functionally true right-sided and nonright
      sided children, with the latter having 1 or more left-sided or indeterminate
      functions (eye, hand, foot). METHODS: The transversal relationship of the primary
      teeth was determined from dental casts of 1,835 young African American (60%) and
      Caucasian (40%) children in a cross-sectional sample at a mean age of 8.5 years.
      Hand, foot, and eye preferences (right, left, or indeterminate) were recorded at
      the age of 4 years during the same collaborative perinatal study. The prevalences
      of left and right crossbites were compared between true right-sided and mixed or
      completely nonright-sided children using chi-square analysis. RESULTS: Unilateral
      crossbite occurred in 140 cases with a complete set of laterality tests: 65 were
      right-sided and 75 left-sided. True right-sided children had more bilaterally
      symmetric occlusions and less crossbite on the right side than those having
      nonright-sidedness in their functions, with the differences being statistically
      significant (P<.01). CONCLUSIONS: These results point to anatomical relationships
      between the structures supporting the occlusion, the asymmetric neurocranium, and
      the cranial base. This suggests variable unilateral compensatory growth after
      unbalanced fetal asymmetry, modified by sidedness and the growth-stimulating
      effects of early lateralized functions and oral habits.

PMID- 16294939
TI  - Classification and treatment of urticaria: a brief review.

PMID- 16294940
TI  - It's a wrap: the use of wet pajamas in wet-wrap dressings for atopic dermatitis.

PMID- 16294941
TI  - What's your assessment? Infected dermatitis with auto-eczematization.

PMID- 16294942
TI  - Cryomold use in Mohs' micrographic surgery.

PMID- 16294943
TI  - Vaccine and drug storage.

PMID- 16294944
TI  - Etanercept injection site reaction.

PMID- 16294945
TI  - Tuberous sclerosis complex.

PMID- 16294946
TI  - The new (or at least newer) kids on the block: new technology in wound care.

PMID- 16294947
TI  - Living with pityriasis rubra pilaris.

PMID- 16294948
TI  - Diseases of the epidermis: psoriasis.

PMID- 16294950
TI  - I'm my own cytokine.

PMID- 16294949
TI  - FDA approves mandatory risk management program for isotretinoin.

PMID- 16294953
TI  - Ni-NiO-Ni tunnel junctions for terahertz and infrared detection.
AB  - We present complete experimental determinations of the tunnel barrier parameters
      (two barrier heights, junction area, dielectric constant, and extrinsic series
      resistance) as a function of temperature for submicrometer Ni-NiO-Ni thin-film
      tunnel junctions, showing that when the temperature-invariant parameters are
      forced to be consistent, good-quality fits are obtained between I-V curves and
      the Simmons equation for this very-low-barrier system (measured phi approximately
      0.20 eV). A splitting of approximately 10 meV in the barrier heights due to the
      different processing histories of the upper and lower electrodes is clearly
      shown, with the upper interface having a lower barrier, consistent with the
      increased effect of the image potential at a sharper material interface. It is
      believed that this is the first barrier height measurement with sufficient
      resolution for this effect to be seen. A fabrication technique that produces high
      yields and consistent junction behavior is presented as well as the preliminary
      results of inelastic tunneling spectroscopy at 4 K that show a prominent peak at 
      59 meV, shifted slightly with respect to the expected transverse optic phonon
      excitation in bulk NiO but consistent with other surface-sensitive experiments.
      We discuss the implications of these results for the design of efficient
      detectors for terahertz and IR radiation.

PMID- 16294954
TI  - Cryogenic optical performance of the ASTRO-F SiC telescope.
AB  - The lightweight cryogenic telescope on board the Japanese infrared astronomical
      satellite, ASTRO-F, which is scheduled to be launched early in 2006, forms an F/6
      Ritchey-Chretien system with a primary mirror of 710 mm in diameter. The mirrors
      of the ASTRO-F telescope are made of sandwich-type silicon carbide (SiC)
      material, comprising a porous core and a chemical-vapor-deposited coat of SiC on
      the surface. To estimate the optical performance of the flight model telescope,
      the telescope assembly was tested at cryogenic temperatures, the total wavefront
      errors of which were measured by an interferometer from outside a liquid-helium
      chamber. As a result, the wavefront error obtained at 9 K shows that the imaging
      performance of the ASTRO-F telescope is diffraction limited at a wavelength of
      6.2 microm, which is a little worse than our original goal of diffraction-limited
      performance at 5.0 microm.

PMID- 16294955
TI  - Enlarging the depth of focus by filtering in the phase-space domain.
AB  - The ambiguity function was employed as a merit function to design an optical
      system with a high depth of focus. The ambiguity function with the desired
      enlarged-depth-of-focus characteristics was obtained by using a properly designed
      joint filter to modify the ambiguity function of the original pupil in the phase
      space domain. From the viewpoint of the filter theory, we roughly propose that
      the constraints of the spatial filters that are used to enlarge the focal depth
      must be satisfied. These constraints coincide with those that appeared in the
      previous literature on this topic. Following our design procedure, several sets
      of apodizers were synthesized, and their performances in the defocused imagery
      were compared with each other and with other previous designs.

PMID- 16294957
TI  - Terahertz paintmeter for noncontact monitoring of thickness and drying progress
      in paint film.
AB  - We propose a paintmeter for noncontact and remote monitoring of the thickness and
      drying progress of a paint film based on the time-of-flight measurement of the
      echo signal of a terahertz (THz) electromagnetic pulse. The proposed method is
      effectively applied to two-dimensional mapping of the painting thickness
      distribution for single-layer and multilayer paint films. Furthermore, adequate
      parameters for the drying progress are extracted from the THz pulse-echo signal
      and effectively applied to monitor the wet-to-dry transformation. The THz
      paintmeter can be a powerful tool for quality control of the paint film on the in
      process monitoring of car body painting.

PMID- 16294956
TI  - Process control of laser conduction welding by thermal imaging measurement with a
      color camera.
AB  - Conduction welding offers an alternative to keyhole welding. Compared with
      keyhole welding, it is an intrinsically stable process because vaporization
      phenomena are minimal. However, as with keyhole welding, an on-line process
      monitoring system is advantageous for quality assurance to maintain the required
      penetration depth, which in conduction welding is more sensitive to changes in
      heat sinking. The maximum penetration is obtained when the surface temperature is
      just below the boiling point, and so we normally wish to maintain the temperature
      at this level. We describe a two-color optical system that we have developed for
      real-time temperature profile measurement of the conduction weld pool. The key
      feature of the system is the use of a complementary metal-oxide semiconductor
      standard color camera leading to a simplified low-cost optical setup. We present
      and discuss the real-time temperature measurement and control performance of the
      system when a defocused beam from a high power Nd:YAG laser is used on 5 mm thick
      stainless steel workpieces.

PMID- 16294958
TI  - Fabrication of alignment structures for a fiber resonator by use of deep
      ultraviolet lithography.
AB  - We present a novel method to mount and align an optical-fiber-based resonator on
      the flat surface of an atom chip with ultrahigh precision. The structures for
      mounting a pair of fibers, which constitute the fiber resonator, are produced by
      a spin-coated SU-8 photoresist technique by use of deep-UV lithography. The
      design and production of the SU-8 structures are discussed. From the measured
      finesses we calculate the coupling loss of the SU-8 structures acting as a kind
      of fiber splice to be smaller than 0.013 dB.

PMID- 16294959
TI  - Analysis of a micropolarizer array-based simultaneous phase-shifting
      interferometer.
AB  - Recent technological innovations have enabled the development of a new class of
      dynamic (vibration-insensitive) interferometer based on a CCD pixel-level phase
      shifting approach. We present theoretical and experimental results for an
      interferometer based on this pixelated phase-shifting technique. Analyses of
      component errors and instrument functionality are presented. We show that the
      majority of error sources cause relatively small magnitude peak-to-valley errors
      in measurement of the order of 0.002-0.005lambda. These errors are largely
      mitigated by high-rate data acquisition and consequent data averaging.

PMID- 16294961
TI  - Computational manufacturing as a bridge between design and production.
AB  - Computational manufacturing of optical coatings is a research area that can be
      placed between theoretical designing and practical manufacturing in the same way
      that computational physics can be placed between theoretical and experimental
      physics. Investigations in this area have been performed for more than 30 years
      under the name of computer simulation of manufacturing and monitoring processes.
      Our goal is to attract attention to the increasing importance of computational
      manufacturing at the current state of the art in the design and manufacture of
      optical coatings and to demonstrate possible applications of this research tool.

PMID- 16294960
TI  - Design and fabrication of a freeform phase plate for high-order ocular aberration
      correction.
AB  - In recent years it has become possible to measure and in some instances to
      correct the high-order aberrations of human eyes. We have investigated the
      correction of wavefront error of human eyes by using phase plates designed to
      compensate for that error. The wavefront aberrations of the four eyes of two
      subjects were experimentally determined, and compensating phase plates were
      machined with an ultraprecision diamond-turning machine equipped with four
      independent axes. A slow-tool servo freeform trajectory was developed for the
      machine tool path. The machined phase-correction plates were measured and
      compared with the original design values to validate the process. The position of
      the phase-plate relative to the pupil is discussed. The practical utility of this
      mode of aberration correction was investigated with visual acuity testing. The
      results are consistent with the potential benefit of aberration correction but
      also underscore the critical positioning requirements of this mode of aberration
      correction. This process is described in detail from optical measurements,
      through machining process design and development, to final results.

PMID- 16294962
TI  - Microstructured light guides overcoming the two-dimensional concentration limit.
AB  - Light guides are employed to homogenize an illumination distribution, to
      translate cross-sectional beam shapes, and to provide concentration.
      Microstructures enhance the performance of light guides based on the selective
      mixing of direction vector components in the two-dimensional phase space
      (etendue) that is perpendicular to the system's optical axis. For linear
      concentrators we find that the microstructured light guide beats the two
      dimensional concentration limit and roughly allows for a three-dimensional
      concentration ratio. This result is verified in simulation and experiment.

PMID- 16294963
TI  - Transverse load and orientation measurement with multicore fiber Bragg gratings.
AB  - We demonstrate the sensitivity of Bragg gratings in a multicore fiber to
      transverse load. The Bragg peaks are split because of stress-induced
      birefringence, the magnitude of which depends upon the load and grating position
      relative to the load axis. Experiments show that a set of gratings in a four-core
      fiber can measure a load axis angle to +/- 5 degrees and a load magnitude to +/-
      15 N m(-1) up to 2500 N m(-1). We consider alternative designs of multicore fiber
      for optimal load sensing and compare experimental and modeled data.

PMID- 16294964
TI  - Circular acoustogyration effect on gold nanoparticles grown on indium tin oxide.
AB  - Gold nanoparticles deposited on indium-tin-oxide coated substrates show
      substantial circularly polarized acoustically induced light gyration (AILG) at
      liquid-helium temperature. The effect was observed only during simultaneous
      treatment by two coherent acoustic waves with basic frequencies of 0.8-1.6 MHz
      and corresponding coherent double-frequency acoustical components. It was found
      that increasing the basic acoustical frequency to 1.6 MHz led to suppression of
      the effect. ATi:sapphire laser with a pulse duration of approximately 80 fs
      allowed us to achieve the maximal value for the AILG. Enhancement of the pulse
      duration higher than 200 fs also substantially diminished the effect. The
      maximally achieved value of the AILG susceptibility (described by a fourth-order
      axial tensor) caused by the circularly polarized acoustical probe field at an
      acoustical power density of approximately 3 W/cm2 at T = 4.2 K was equal to
      approximately 7.8 deg/mm for the circular acoustical wave polarization. The
      maximal AILG coefficient is achieved for samples that possess minimal
      resistivity. The investigated composites possess an acoustically induced
      helicoidal grating that disappeared 20 s after switching off the acoustical
      fields.

PMID- 16294965
TI  - Faraday current sensor with temperature monitoring.
AB  - We present a novel optical current sensor based on the Faraday effect that
      incorporates a temperature monitoring system. The monitoring element is a
      temperature-dependent birefringent plate placed at the Faraday sensor head.
      Measurement of the plate retardation permits compensation for the temperature
      dependence of the Verdet constant. Validation experiments are presented and
      discussed.

PMID- 16294966
TI  - Modeling of the frequency- and temperature-dependent absorption coefficient of
      long-wave-infrared (2-25 microm) transmitting materials.
AB  - A semiempirical multiphonon model based on quantum-mechanical oscillators under a
      Morse potential is applied to the absorption coefficient of far-infrared
      transmitting materials. Known material properties are combined with absorption
      coefficient data to fit the empirical parameters of the model. This provides an
      accurate means of predicting the intrinsic absorption of the materials in their
      multiphonon regions. Extinction data are obtained by measuring material
      transmittances with a Fourier-transform spectrometer and comparing them with the
      lossless transmittances predicted by Sellmeier models. Where appropriate, scatter
      models are used to separate the extinction into loss due to scatter and
      absorption. Data and model parameters are presented for GaAs, GaP, ZnS, and ZnSe.

PMID- 16294967
TI  - Influence of thermal annealing and ultraviolet light irradiation on LaF3 thin
      films at 193 nm.
AB  - Lanthanum fluoride (LaF3) thin films were prepared by resistive heating
      evaporation and electron-beam gun evaporation under the same deposition rate,
      deposition substrate temperature, and vacuum pressure. The coated LaF3 films were
      then treated by heat annealing and UV light irradiation. The optical properties,
      microstructures, stress, and laser-induced damage threshold (LIDT) at a
      wavelength of 193 nm were investigated. The surface roughness, optical loss,
      stress, and LIDT of the films were improved after the annealing. The films had
      better properties when irradiated by UV light as compared with heat annealing.

PMID- 16294969
TI  - Chromatic compensation in the near-field region: shape and size tunability.
AB  - We report a diffractive-lens triplet with which to achieve wavelength
      compensation in the near field diffracted by any aperture. On the one hand, the
      all-diffractive triplet allows us to tune, in a sequential way, the Fresnel
      irradiance shape to be achromatized by changing the focal length of one
      diffractive lens. On the other hand, we can adjust the scale of the chromatically
      compensated Fresnel diffraction field by shifting the aperture along the optical
      axis. Within this framework, we present an extremely flexible white-light Fresnel
      plane array illuminator based on the kinoform sampling filter. A variable
      compression ratio and continuous selection of the output pitch are the most
      appealing features of this novel application.

PMID- 16294968
TI  - Wave-optical evaluation of interference fringes and wavefront phase in a hard-x
      ray beam totally reflected by mirror optics.
AB  - The intensity flatness and wavefront shape in a coherent hard-x-ray beam totally
      reflected by flat mirrors that have surface bumps modeled by Gaussian functions
      were investigated by use of a wave-optical simulation code. Simulated results
      revealed the necessity for peak-to-valley height accuracy of better than 1 nm at
      a lateral resolution near 0.1 mm to remove high-contrast interference fringes and
      appreciable wavefront phase errors. Three mirrors that had different surface
      qualities were tested at the 1 km-long beam line at the SPring-8/Japan
      Synchrotron Radiation Research Institute. Interference fringes faded when the
      surface figure was corrected below the subnanometer level to a spatial resolution
      close to 0.1 mm, as indicated by the simulated results.

PMID- 16294970
TI  - Phase retrieval errors in standard Fourier fringe analysis of digitally sampled
      model interferograms.
AB  - We investigate the reliability of phase retrieval by use of the fringe Fourier
      analysis method for measuring the displacements of facets during the growth of
      equilibriumlike-shaped crystals. The mean phase change between two successive
      interferometric images contains an inherent error that emerges from the
      noninteger number of fringes in the image field. The magnitude of the retrieved
      phase error of the ideal fringe pattern is investigated as a function of spatial
      carrier frequency, of the initial phase setting, and of the deviation of the
      number of fringes from the nearest integer value. The suggested modified
      algorithm suppresses the error more than threefold.

PMID- 16294971
TI  - Transmission of digital images consisting of white-light dark solitons.
AB  - A distortion-free digital image is transmitted through parallel propagation of
      white-light photovoltaic dark solitons. The waveguide channels induced by white
      light dark solitons can guide both the laser beam and the white-light beam well.
      We determine experimentally the critical separations of the dark solitons in the
      directions parallel and perpendicular to the crystalline c axis for the given
      crystal thickness.

PMID- 16294972
TI  - Development of a laboratory spectral backscattering instrument: design and
      simulation.
AB  - A typical integrating sphere configuration for measuring backscatter includes a
      conventional cuvette with flat windows. This arrangement results in a significant
      amount of total internal reflection, preventing a large portion of the
      backscattered flux from entering the integrating sphere-detector system. Use of a
      semispherical cuvette overcomes this problem. Monte Carlo simulations of a
      semispherical cuvette window demonstrate that the detected signal varies
      monotonically with the attenuation, depending only on the probability of
      backscattering for a given single scattering albedo. That is, only the total
      backscattering probability matters, regardless of subtle differences in the
      scattering phase function in the backward direction. The system is calibrated by
      use of standard microspheres for which the size distribution and the refractive
      index are known; this makes it possible to compute the exact phase function based
      on Mie theory. We have performed Monte Carlo simulations for various measured
      volume scattering functions and for computed phase functions, using particle
      scattering codes. All the results indicate that the backscattering measurement
      errors are likely to be less than 10%.

PMID- 16294973
TI  - Effect of optical turbulence in the dye medium on the bandwidth of a narrowband,
      high-repetition-rate dye laser.
AB  - An analysis of turbulence in the dye medium of a high-repetition-rate narrowband
      dye laser is presented, and it is shown that the output bandwidth is proportional
      to the turbulence length scale, which depends on the Reynolds number. The length
      scale and the bandwidth both first decrease and then increase as the Reynolds
      number is increased from -200 to -20,000. The observed bandwidth, as we report
      and as in the published literature, confirms the validity of the analysis. A
      Rhodamine 6G grazing-incidence grating, stable dye laser transversely pumped by a
      copper-vapor laser was used in the experiments.

PMID- 16294974
TI  - Effective second-order nonlinearity in acentric optical crystals with low
      symmetry.
AB  - We derive explicit expressions in the frame of the optical indicatrix for the
      second-order effective nonlinearity in biaxial crystals with point groups 2, m,
      and 1, governing the conversion efficiency in three-wave nonlinear optical
      interactions. The tabulated expressions for the monoclinic symmetry classes 2 and
      m are valid for all possible orientations of the optical indicatrix relative to
      the crystallographic frame and for propagation along an arbitrary direction
      outside the principal planes. They can be used for direct estimation of the
      effective nonlinearity in the same frame where the phase-matching loci are
      calculated. The relevant properties and conventions used for the newly emerging
      acentric monoclinic crystals belonging to the borate family are summarized and
      tabulated. The derivations are expected to help establish adherence to uniform
      nomenclature and conventions for these novel inorganic nonlinear crystals, and to
      eliminate ambiguity and increasing confusion in the literature and in the
      industrial specifications. The general expressions for the effective nonlinearity
      are reduced for triclinic crystals of point group 1 to simplified forms in the
      principal planes.

PMID- 16294975
TI  - Use of shadows to retrieve water vapor in hazy atmospheres.
AB  - Techniques aimed at retrieving water vapor from satellite data of reflected near
      infrared solar radiation have progressed significantly in recent years. These
      techniques rely on observation of water vapor attenuation of near-infrared solar
      radiation reflected by the Earth's surface. Ratios of measured radiances at
      wavelengths inside and outside water vapor absorbing channels are used for
      retrieval purposes. These ratios partially remove the dependence of surface
      reflectance on wavelength and are used to retrieve the total column water vapor
      amount. Hazy atmospheric conditions, however, introduce errors into this widely
      used technique. A new method based on radiance differences between clear and
      nearby shadowed surfaces, combined with ratios between water vapor absorbing and
      window regions, is presented that improves water vapor retrievals under hazy
      atmospheric conditions. Radiative transfer simulations are used to demonstrate
      the advantage offered by this technique.

PMID- 16294976
TI  - Thermometry for turbulent flames by coherent anti-Stokes Raman spectroscopy with
      simultaneous referencing to the modeless excitation profile.
AB  - An optimal system for temperature measurements by coherent anti-Stokes Raman
      spectroscopy (CARS) in turbulent flames and flows is presented. In addition to a
      single-mode pump laser and a modeless dye laser, an echelle spectrometer with a
      cross disperser is used. This system permits simultaneous measurement of the N2
      CARS spectrum and the broadband dye laser profile. A procedure is developed to
      use software to transform this profile into the excitation profile by which the
      spectrum is referenced. Simultaneous shot-to-shot referencing is compared to
      sequential averaged referencing for data obtained in flat flames and in room air.
      At flame temperatures, the resultant 1.5% imprecision is limited by flame
      fluctuations, indicating that the system may have a single-shot imprecision below
      1%. At room temperature, the 3.8% single-shot imprecision is of the same order as
      the best values reported for dual-broadband pure-rotational CARS. Using the
      unique shot-to-shot excitation profiles, simultaneous referencing eliminates
      systematic errors. At 2000 and 300 K, the 95% confidence intervals are estimated
      to be +/- 20 and +/- 10 K, respectively.

PMID- 16294977
TI  - Sources of health insurance and characteristics of the uninsured: analysis of the
      March 2005 Current Population Survey.

PMID- 16294978
TI  - Here, there, every air. Allergens are everywhere in your facility.

PMID- 16294979
TI  - At one with the Web. Is your site senior-friendly?

PMID- 16294980
TI  - Can you spare a few million? Loan performance at an all-time high.

PMID- 16294981
TI  - Perils and pitfalls. Stay prepared after a promotion.

PMID- 16294982
TI  - Advancing physical therapy practice: the accountable practitioner.

PMID- 16294983
TI  - Historical perspectives of autonomy within the medical profession: considerations
      for 21st century physical therapy practice.
AB  - As a part of the American Physical Therapy Association's (APTA) vision statement,
      by the year 2020, physical therapists "will hold all privileges of autonomous
      practice." This vision statement and the ideals held within it are elemental to
      the direction of our continued growth as a profession. Many members and
      nonmembers, however, appear confused and perhaps even intimidated by the concept
      of autonomous practice. This paper will review and discuss the processes used by
      other health care professions to gain autonomy within the US health care system.
      In particular, the processes used by physicians, which were extremely effective
      and have been used as a template by many other health professions, including
      physical therapy. Further discussion will focus on the physical therapy
      profession, emphasizing the parallels with medicine and considering many issues
      relevant to the goal of autonomous practice. By understanding the past and
      considering the present, readers will develop an appreciation of (1) the
      foundation for autonomous practice in health care, (2) the vision of the APTA and
      why the profession is well positioned to achieve this vision, and (3) the factors
      we need to consider to hold (and maintain) all privileges of autonomous practice.

PMID- 16294984
TI  - Pulmonary emboli: the differential diagnosis dilemma.
AB  - Pulmonary embolism is a rare but serious medical condition, with an estimated
      mortality of 5% to 20%. Many patients receiving physical therapy may be at risk
      for developing pulmonary embolism, especially after periods of immobilization or
      surgery. Patients presenting with dyspnea, chest pain, or tachypnea, particularly
      after trauma or surgery, have an increased likelihood of pulmonary embolism.
      Clinical prediction rules have been developed, which can aid the practitioners in
      assessing the risk a patient has for developing pulmonary embolism. The present
      clinical commentary discusses the existing evidence for screening patients for
      pulmonary embolism. To illustrate the importance of the screening examination, a
      patient is presented who was referred to physical therapy 5 days after cervical
      discectomy and fusion. This patient was subsequently referred for medical
      evaluation and a confirmatory diagnosis of pulmonary embolism.

PMID- 16294985
TI  - Clinical diagnosis of vertebrobasilar insufficiency: resident's case problem.
AB  - STUDY DESIGN: Resident's case problem. BACKGROUND: Vertigo and visual
      disturbances are common symptoms associated with vertebrobasilar insufficiency
      (VBI), but the physical examination procedures to verify the existence of VBI
      have not been validated in the literature. The objective of this resident's case
      problem is to demonstrate how a patient's complaint of vertigo and visual
      disturbances, combined with positive clinical examination findings, can be a
      potential medical screening tool for VBI. DIAGNOSIS: The patient in this report
      was initially referred to physical therapy for neck pain. However, the patient's
      chief concerns identified during the history were (1) vertigo, (2) visual
      disturbances, (3) headache, and (4) right shoulder region pain. Clinical VBI
      tests were performed, whereby the patient's vertigo and visual disturbances were
      reproduced with cervical spine extension. The patient was sent back to the
      referring physician to be evaluated for possible VBI. Diagnostic imaging tests
      were ordered. Carotid ultrasound revealed 80% to 90% stenosis in the proximal
      left internal carotid artery, and magnetic resonance angiography of the
      extracerebral vessels showed greater than 90% stenosis of the left internal
      carotid artery. DISCUSSION: VBI may be present in patients with subjective
      reports of vertigo and visual disturbances that are reproduced with VBI physical
      examination procedures.

PMID- 16294986
TI  - Cancer as a cause of low back pain in a patient seen in a direct access physical
      therapy setting.
AB  - STUDY DESIGN: Resident's case problem. BACKGROUND: This paper describes the
      clinical course of a patient with low back pain (LBP) and left lower extremity
      pain and tingling, and how the physical therapist used clinical examination
      findings and a lack of improvement with conservative measures to initiate further
      medical evaluation, which resulted in a diagnosis of cancer as the primary cause
      of the patient's low back and hip pain. DIAGNOSIS: A 45-year-old man with chief
      complaints of left-sided LBP, left posterior thigh pain, and tingling along the
      anterolateral aspect of his left lower extremity was initially seen by a physical
      therapist in a direct access setting. Several components of the patient's history
      and physical examination were consistent with a mechanical neuromusculoskeletal
      dysfunction. However, there were signs and symptoms present that may have been
      suggestive of more serious underlying disease. Specifically, the patient's most
      intense pain was in the evening and into the night and an atypical pattern of
      restricted motion at the left hip was noted. Therefore, the physical therapist
      recommended that the patient schedule an appointment with his physician for
      medical evaluation. A short-term course of physical therapy treatment was also
      undertaken to address neuromusculoskeletal impairments. Despite 5 physical
      therapy visits over the course of a month, while the patient waited for his
      scheduled physician appointment, the patient's condition gradually worsened.
      After medical evaluation, the patient was eventually diagnosed with small cell
      carcinoma of the lung, with metastases to the spine and pelvis. Despite 2 cycles
      of chemotherapy, the patient succumbed to the cancer 5 months after he was first
      seen in physical therapy. DISCUSSION: It is important that physical therapists
      have an understanding of the clinical findings associated with the presence of
      serious underlying diseases causing LBP, as this information provides guidance as
      to when communication with the patient's physician is warranted.

PMID- 16294987
TI  - Cervical radiculopathy or Parsonage-Turner syndrome: differential diagnosis of a
      patient with neck and upper extremity symptoms.
AB  - STUDY DESIGN: Resident's case problem. BACKGROUND: The signs and symptoms of
      cervical radiculopathy (CR) warrant the consideration of several other conditions
      in CR's differential diagnosis. One condition that may mimic CR, which is not
      well known amongst physical therapists, is Parsonage-Turner syndrome (PTS). PTS
      is characterized by an onset of intense pain that typically subsides within days
      to weeks. However, as pain subsides, weakness and/or paralysis may develop in
      upper extremity muscles. The purpose of this resident's case problem is to
      describe a patient who presented to our clinic with a diagnosis of CR, but had
      findings consistent with PTS. DIAGNOSIS: The patient was a 43-year-old male
      referred to physical therapy with a diagnosis of CR. He had a previous episode of
      CR 1 year ago that was treated successfully. He had positive magnetic resonance
      imaging findings of structural abnormalities suggestive of causative factors for
      CR. The patient was treated for CR with thoracic and cervical spine manipulations
      and intermittent cervical traction. The initial acute severe pain subsided, but
      weakness in the upper extremity worsened. Diagnosis of PTS was made upon
      exclusion of other potential confounding diagnoses and the findings of
      fibrillation potentials and positive waves in electrodiagnostic studies.
      DISCUSSION: CR and PTS are characterized by pain in the cervical spine, shoulder,
      and upper extremity. CR generally has an insidious onset, while PTS has a rapid
      onset of intense pain. Symptoms of CR are exacerbated with neck movements, while
      symptoms related to PTS should not be exacerbated with neck movements. In
      patients that do not respond to conventional therapy and have a progression of
      upper extremity muscle weakness, regardless of decreased pain, the diagnosis of
      PTS should be considered.

PMID- 16294988
TI  - Identification and management of 2 femoral shaft stress injuries.
AB  - STUDY DESIGN: Resident's case problem. BACKGROUND: Although femoral shaft stress
      fractures in the general population are rare, they are more common among
      endurance athletes and military recruits. Such individuals presenting with a
      complaint of hip, thigh, or knee pain should raise suspicion for femoral shaft
      stress injury. A United States Military Academy cadet presented to West Point's
      Physical Therapy-Sports Medicine clinic with a complaint of thigh pain related to
      training with the local marathon team. A second cadet presented to the same
      clinic during Cadet Basic Training with a complaint of vague but increasing hip,
      thigh, and knee pain. DIAGNOSIS: Both cadets were suspected of having femoral
      stress injuries, based on clinical exams, and both diagnoses were confirmed with
      diagnostic imaging. The 2 cadets were both treated conservatively with
      progressive rehabilitation once healing was confirmed with radiographs. They both
      responded favorably to conservative management and returned to full athletic
      activity at approximately 12 weeks. DISCUSSION: Symptoms from a femoral shaft
      stress fracture can be vague and mimic those of other etiologies. Providers
      should consider a broad differential diagnosis, to include femoral shaft stress
      fracture, when treating endurance athletes and military recruits with anterior
      hip, thigh, or knee pain. Proper imaging confirms the diagnosis and sequential
      radiographs assist in rehabilitation planning.

PMID- 16294989
TI  - Risk determination for patients with direct access to physical therapy in
      military health care facilities.
AB  - STUDY DESIGN: Nonexperimental, retrospective, descriptive design. OBJECTIVES:
      This study was designed to ascertain whether direct access to physical therapy
      placed military health care beneficiaries at risk for adverse events related to
      their management. BACKGROUND: Military health care beneficiaries have the option
      at most US military hospitals and clinics to first enter the health care system
      through physical therapy by direct access, without referral from another
      privileged health care provider. This level of autonomous practice incurs broad
      responsibilities and raises concern regarding the delivery of safe, competent,
      and appropriate patient care administered by physical therapists (PTs) when
      patients are not first examined and then referred by a physician or other
      privileged health care provider. While military PTs practice autonomously in a
      variety of health care settings, they do not work independently within any
      facility. Military PTs and physicians rely on one another for sharing and
      collaboration of information regarding patient care and clinical research as
      warranted. Additionally, military PTs are indirectly supervised by physicians.
      METHODS AND MEASURES: To reduce provider bias, a retrospective analysis was
      performed at 25 military health care sites (6 Army, 11 Navy, and 8 Air Force) on
      patients seen in physical therapy from October 1999 through January 2003. During
      this 40-month period, 95 PTs (88 military and 7 civilian) were credentialed to
      provide care throughout the various medical sites. Descriptive statistics were
      analyzed for total workload, number of new patients seen with and without
      referral, documented patient adverse events reported to each facility's Risk
      Management Office, and any disciplinary or legal action against a physical
      therapist. RESULTS: During the 40-month observation period, 472 013 patient
      visits were recorded. Of these, 112 653 (23.9%) were new patients, with 50 799
      (45.1%) of the new patients seen through direct access without physician
      referral. Throughout the 40-month data collection period, there were no reported
      adverse events resulting from the PTs' diagnoses or management, regardless of how
      patients accessed physical therapy services. Additionally, none of the PTs had
      their credentials or state licenses modified or revoked for disciplinary action.
      There also had been no litigation cases filed against the US Government involving
      PTs during the same period. CONCLUSIONS: The findings from this preliminary study
      clearly demonstrate that patients seen in military health care facilities are at
      minimal risk for gross negligent care when evaluated and managed by PTs, with or
      without physician referral. The significance of these findings with respect to
      direct access is important for not only our beneficiaries but also our profession
      and the facilities in which we practice.

PMID- 16294992
TI  - Follow-up on IUDs.

PMID- 16294993
TI  - Protein recommendation questioned.

PMID- 16294994
TI  - Neuropsychiatric testing for ADHD.

PMID- 16294995
TI  - Designing your Web site.

PMID- 16294997
TI  - National provider ID numbers.

PMID- 16294996
TI  - Inconsolable crying in a baby.

PMID- 16294998
TI  - Patient information. Health benefits of oils.

PMID- 16294999
TI  - The quest for a good night's sleep. Behavioral change and hypnotics offer
      effectiveness.

PMID- 16295000
TI  - Psoriatic arthritis: a holistic approach to management.

PMID- 16295001
TI  - Hemangiomas in infancy and childhood: psychosocial issues require close
      attention.

PMID- 16295002
TI  - Worth the weight: pregnancy after gastric bypass surgery.

PMID- 16295003
TI  - COX-2 inhibitors and the heart: putting risk in perspective.

PMID- 16295004
TI  - A tangled web: don't miss multiple sclerosis.

PMID- 16295005
TI  - Changed from the inside out.

PMID- 16295006
TI  - Faces of HIV/AIDS and substance abuse in Native American communities.

PMID- 16295007
TI  - The changing face of HIV/AIDS among Native populations.
AB  - AIDS has steadily increased in recent years, becoming the ninth leading killer of
      Native people between the ages of 15 and 44. In 2003, the Centers for Disease
      Control and Prevention (CDC) reported that ethnic minorities account for more
      than 71% of all reported AIDS cases and that there are still increases in AIDS
      cases in the American Indian population. Despite the work that has been done
      related to HIV/AIDS, there remain some major challenges in the prevention of
      HIV/AIDS in Native communities. Yet, there are changes on the horizon and these
      changes bring hope to Native communities in the ongoing battle to decrease HIV
      and AIDS. This article details information about the biological, social, economic
      and behavioral cofactors related to the rise in HIV/AIDS in Native communities
      and follows with issues related to special populations and consideration of the
      unique needs of prevention in these subpopulations. The need for norming of HIV
      testing is discussed as is the need for Native-specific programs and
      interventions. Finally, changes in the recognition of the culturally specific
      needs of Native people are noted and new resources are presented.

PMID- 16295008
TI  - Holistic Native network: integrated HIV/AIDS, substance abuse, and mental health
      services for Native Americans in San Francisco.
AB  - The Holistic Native Network provides a model for integrated HIV/AIDS, substance
      abuse and mental health services in a cultural context. Funded in 2002 by a grant
      from the Health Resources and Services Administration (HRSA) Special Projects of
      National Significance (SPNS) initiative, the Holistic Native Network is a
      collaboration of the Native American Health Center and Friendship House
      Association of American Indians, two community-based organizations with
      facilities in San Francisco and Oakland. Substance abuse and mental health
      services are integrated into primary HIV/AIDS medical care. San Francisco has the
      largest population of Native Americans with HIV/AIDS in the country. Since its
      inception, 45 Native Americans with HIV/AIDS have been enrolled in the Holistic
      Native Network. These clients were surveyed upon admission and at three months in
      treatment. The results indicated positive changes in quality of life. The success
      of this program lies in the way that culture and community is included at every
      stage of service provision. From outreach to case management to substance abuse
      and mental health services, the Holistic Native Network meets the spiritual,
      medical and psychosocial needs of HIV+ Native Americans.

PMID- 16295009
TI  - HIV/AIDS and Native Americans: the health departments' response.
AB  - For some time, state health department HIV/AIDS programs have worked with
      communities of color to address their unmet needs. Because of the need for a
      holistic approach to the multiple issues impacting these communities, efforts to
      address HIV/AIDS in Native American communities are often integrated into
      programs addressing related issues, such as substance abuse, mental health and
      other STDs. Building upon a recent report from the National Alliance of State and
      Territorial AIDS Directors (NASTAD), this article will review the numerous
      challenges state and local health departments face in supporting HIV/AIDS-focused
      health and human services in Native American communities and how some health
      departments have worked with Native American communities to respond to these
      challenges. A series of recommendations and next steps for health departments
      seeking to improve services in Native American communities will be offered.

PMID- 16295010
TI  - Native women, violence, substance abuse and HIV risk.
AB  - Violence has become a critical public health issue in the United States. It has
      had a particularly devastating impact on the health and well being of Native
      American women and children. The relationship between aggression and substance
      use is an intrinsic one: Native women often bear the brunt of violence in
      drinking situations, which places them and their children at extremely high risk
      for physical and sexual abuse. In urban environments, many Native American women
      find themselves in adult relationships that mirror the abuse they experienced and
      witnessed as children or adolescents. Not only does violence often occur while
      substances are being used, but conversely, substance use is a frequent
      consequence of sexual abuse. Clearly, the mental health repercussions of physical
      or sexual abuse are often severe. Trauma is associated not only with
      psychological distress, but also with risky behavior and social role impairment.
      Traumatized women engaging in substance abuse and unsafe sex are at high risk for
      contracting HIV/AIDS. This article explores the intersection of substance abuse,
      sexual and physical abuse, and increased HIV risk among urban Native American
      women in the San Francisco Bay Area.

PMID- 16295011
TI  - Art therapy as emotional and spiritual medicine for Native Americans living with
      HIV/AIDS.
AB  - This article describes the intricate challenges of bringing mental health
      services to isolated, guarded urban HIV-positive Native Americans suffering from
      chronic trauma-related illnesses and imbalances, depression, anxiety, substance
      abuse, thought disorders and trauma-based characterological disorders. It
      explores the integration of art therapy, Bowen Family Systems Therapy and in-home
      therapy in the Family & Child Guidance Clinic's attempt to provide support to a
      population that has profound distrust for "services and treatment," and no
      historical context for psychotherapy. Changing the paradigm of thought is
      essential to providing services that respect culture and history as well as
      addressing current presenting issues. Art therapy and in-home therapy support
      those community members who are flooded emotionally, but have difficulty speaking
      about their internal processes.

PMID- 16295012
TI  - Cultural investment: providing opportunities to reduce risky behavior among gay
      American Indian males.
AB  - Many gay American Indian (GAI) men feel alienated from their tribal, ceremonial
      and social communities because of homophobia and heterosexism. As a result, they
      often turn to their local gay community for social participation and sex
      opportunities. It is no secret that a significant aspect of some gay communities
      is socializing in local bars and clubs. The gay bar scene makes healthy living
      difficult for Native American gay men. This is especially the case for those who
      are in alcohol or drug recovery. In response, gay Native men's support groups are
      attempting to make available a cultural alternative to the double bind of
      alienation from one's Native community and exposure to substance abuse by
      providing alcohol and substance free opportunities for ceremonial and social
      involvement. The hope is that the men will go to bars less frequently and instead
      turn to Native cultural activities in men's groups for social, spiritual and
      emotional support. The logic of this approach assumes that individuals who are
      culturally invested in a community will gain a level of self and social
      acceptance, making them less likely to abuse substances and put themselves at
      risk for HIV infection. The information presented in this article comes from over
      six years of ethnographic research among GAI men concerning self and social
      acceptance, HIV/AIDS and American Indian GLBT identity.

PMID- 16295013
TI  - Culturally appropriate HIV/AIDS and substance abuse prevention programs for urban
      Native youth.
AB  - This article will examine HIV/AIDS and substance abuse prevention for urban
      Native youth in Oakland, California. It will highlight the Native American Health
      Center's Youth Services programs. These programs incorporate solutions based on a
      traditional value system rooted in Native culture and consisting of youth
      empowerment, leadership training, prevention activities, traditional cultural
      activities and wellness and life skills education. They aim to reduce HIV/AIDS
      and substance abuse risk for American Indian/Alaska Native (AI/AN) youth through
      structured, community-based interventions. The Youth Services Program's events,
      such as the Seventh Native American Generation and the Gathering of Native
      Americans, offer effective and culturally relevant ways of teaching youth about
      American Indian/Alaska Native history, intergenerational trauma, and traditional
      Native culture. Satisfaction surveys gathered from these youth provide invaluable
      data on the positive effects of these prevention efforts. The need for culturally
      relevant and culturally appropriate HIV/AIDS and substance abuse prevention
      programs for urban AI/AN youth is apparent. These prevention efforts must be
      creatively integrated into the multidimensional and complex social structures of
      Native American youth.

PMID- 16295014
TI  - Special Projects of National Significance and the Alaska Tribal Health System: an
      overview of the development of a best practice model for HIV/AIDS care and
      treatment in Alaska.
AB  - This article presents a discussion about the increased risk of the spread of HIV
      among Alaska Natives resulting from high-risk co-occurring conditions and social
      and cultural customs that create barriers to HIV/AIDS prevention education.
      Additionally, an overview of the unique structure of the Alaska Tribal Health
      System and how the Health Resources Service Administration's (HRSA) American
      Indian Alaska Native Special Projects of National Significance Initiatives (AI/AN
      SPNS) have been a critical component in creating the foundation for the
      development of a best practice model for HIV/AIDS care and treatment in Alaska is
      provided. This article is not a comparative analysis of the Indian Health Care
      System. Rather, it provides a discussion about tribal federalism, the Alaska
      Tribal Health System (ATHS), and the influence the AI/AN SPNS initiatives have
      had on the development of HIV/AIDS care and treatment in Alaska. In order to
      explain how the AI/AN SPNS initiatives have influenced the development of
      HIV/AIDS care and treatment in Alaska, it is also necessary to understand the
      evolution of the ATHS and how this system is unique compared to other tribal,
      private, and public health care systems throughout the United States.

PMID- 16295015
TI  - Oral disease prevalence among HIV-positive American Indians in an urban clinic.
AB  - Abstract-According to Centers for Disease Control and Prevention (CDC) estimates,
      there have been almost 930,000 AIDS cases diagnosed at the end of 2003 in the
      United States. About 3,000 of those infected were American Indian and Alaska
      Natives (AI/ANs). Persons with HIV and AIDS have been shown to have increased
      risk of dental and periodontal disease. Unfortunately, there are no publications
      on dental disease and AI/ANs with HIV/AIDS. This study addresses this shortcoming
      by examining the relationship between dental health, drug use, and HIV among
      AI/AN patients in an urban setting. The study included a consecutive chart review
      of 51 AI/AN HIV-positive dental patients seen from 2001 to 2004 at the Native
      American Health Center in San Francisco. Results showed that 55% had moderate or
      severe periodontal disease, 80.4% had tooth decay, and 88.2% had missing teeth.
      Substance users had more dental caries or decayed teeth than non-substance users
      (88% versus 73%). The average rate for decayed, missing or filled teeth (DMFT)
      among the total sample was 18.73%. This chart review study suggests that dental
      disease is more prevalent in AI/ANs with HIV/AIDS when compared to the general
      population and AI/AN data from the Indian Health Service.

PMID- 16295016
TI  - Using motivational interviewing to promote HIV testing at an American Indian
      substance abuse treatment facility.
AB  - Alcohol and drug use are associated with increased risk of HIV/AIDS. American
      Indians and Alaska Natives (AI/AN) have high rates of alcohol and other drug use,
      as well as a high incidence of unsafe sex behaviors and injection drug use
      practices. Indicators of AI/AN HIV risks involving sexual activity include high
      rates of STDs, such as gonorrhea, chlamydia, and syphilis. Despite these facts,
      the prevalence of HIV infection among AI/AN is not well known. The present study
      is part of a HRSA-funded SPNS HIV/AIDS health initiative, one goal of which is to
      increase the number of HIV-positive individuals who know their HIV status. To
      meet the goal of the SPNS project, patients in an inpatient alcohol and drug
      treatment center were provided with an HIV prevention educational presentation
      followed by one-on-one HIV counseling. Motivational interviewing was used in the
      counseling sessions to aid participants in recognizing their risk status and
      making a decision to be HIV tested. Results show that of the 134 who agreed to
      one-on-one HIV counseling and 105 (78%) returned for their results.

PMID- 16295017
TI  - In the house of the epidemic.

PMID- 16295019
TI  - Medical interventions at the end of life: what is appropriate and who is
      responsible?

PMID- 16295018
TI  - HIV prevalence and correlates of receptive needle sharing among injection drug
      users in the Mexican-U.s. border city of Tijuana.
AB  - Injection drug use is a growing but understudied problem in Tijuana, a city
      situated on the northwestern Mexico-U.S border. The authors studied factors
      associated with receptive needle sharing in an effort to inform prevention
      activities. In 2003, street-recruited injection drug users (IDUs) in Tijuana
      underwent interviews on injection risk behaviors and rapid HIV antibody tests.
      Logistic regression was used to identify correlates of receptive needle sharing
      at the last injection episode. Of 402 IDUs, 87.6% were male; the median age was
      34. HIV prevalence was 4.01% (95% CI: 2.29-6.51). One third reported receptive
      needle sharing at last injection. Factors independently associated with receptive
      needle sharing were years living in Tijuana (Adjusted Odds Ratio [AdjOR]= 0.97
      per year, 95% CI: 0.96-0.99), being bisexual/homosexual (AdjOR=2.12; 95% CI: 1.30
      - 3.44), unemployed (AdjOR=2.5; 95% CI: 1.52-4.10), never having an HIV test
      (AOR: 4.02; 95% CI: 2.44-6.60), having friends who placed importance on avoiding
      HIV (AdjOR: 0.36; 95% CI: 0.19-0.68) and last injecting in a shooting gallery
      (AdjOR=1.98; 95% CI: 1.21-3.24). These results underscore the need to increase
      access to voluntary HIV testing and counseling to IDUs and migrants in Tijuana,
      as well as expand access to sterile syringes in an effort to avert widespread HIV
      transmission.

PMID- 16295020
TI  - Safety, diagnostic yield, and therapeutic implications of flexible bronchoscopy
      in patients with febrile neutropenia and pulmonary infiltrates.
AB  - OBJECTIVE: To evaluate the safety, diagnostic yield, and therapeutic implications
      of flexible bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial
      biopsy in patients with febrile neutropenia and pulmonary infiltrates. PATIENTS
      AND METHODS: We retrospectively reviewed the medical records of all patients with
      neutropenic fever and pulmonary infiltrates evaluated by flexible bronchoscopy
      and BAL between January and December 2002 at the Mayo Clinic in Rochester, Minn.
      Appropriate demographic, clinical, microbiological, and histological data and
      procedure-related complications were summarized. Therapeutic decisions
      implemented based on Information obtained by bronchoscopy, and 28-day mortality
      were determined. RESULTS: Thirty-five patients with febrile neutropenia and
      associated pulmonary infiltrates were identified. Flexible bronchoscopy,
      including 35 BALs and 9 transbronchial biopsies, was performed safely (3
      complications). The diagnostic yield of BAL was 49%. Sputum analysis was
      underused (only 34%) but complementary to BAL. The combined diagnostic yield of
      BAL and sputum analysis was 63%. Transbronchial biopsy provided additional
      information to BAL and sputum analysis In only 1 patient and did not
      substantially increase the combined diagnostic yield. The most common diagnoses
      identified were fungal pneumonias (15/35 [43%]) and diffuse alveolar hemorrhage
      (5/35 [14%]). Bronchoscopic findings resulted in management changes in 51% of
      patients. The 28-day mortality rate was 26% and was highest in patients who
      required mechanical ventilatory assistance before bronchoscopy. CONCLUSION: The
      favorable safety record, good diagnostic yield, and frequent therapeutic
      implications support the routine use of BAL for the evaluation of pulmonary
      inflitrates in neutropenic patients. Bronchoalveolar lavage should be combined
      with the analysis of several sputum specimens. Transbronchial biopsy did only
      change the management of 1 patient.

PMID- 16295021
TI  - Prepregnancy exposure to cigarette smoking and subsequent risk of postmenopausal
      breast cancer.
AB  - OBJECTIVE: To examine the association of cigarette smoking before first pregnancy
      with risk of postmenopausal breast cancer in a large population-based cohort.
      PATIENTS AND METHODS: The Iowa Women's Health Study is a prospective cohort study
      of 55- to 69-year-old women at baseline in 1986. In January 1986, a questionnaire
      was mailed to 99,826 postmenopausal women to Identify risk factors for cancer and
      other chronic diseases; 41,836 women responded (42.7% response rate). The primary
      analyses examined the associations among smoking, parity, age at first birth, and
      postmenopausal breast cancer. RESULTS: Of the 37,105 women in the cohort at risk,
      7095 (19%) and 4186 (11%) initiated smoking before and after first pregnancy,
      respectively, and 2017 breast cancers were identified before December 31, 1999.
      Compared with parous women who never smoked, women who began smoking after their
      first full-term pregnancy were not at increased risk of postmenopausal breast
      cancer (multivariate-adjusted risk ratio, 1.03; 95% confidence interval, 0.88
      1.21). However, women who began smoking before their first pregnancy had a
      slightly elevated risk of breast cancer (risk ratio, 1.21; 95% confidence
      Interval, 1.07-1.37). Results were not attenuated by adjustment for age at first
      pregnancy or number of live births. CONCLUSION: These data suggest that cigarette
      smoking is associated with a slightly greater risk of postmenopausal breast
      cancer for women who started smoking before their first full-term pregnancy.

PMID- 16295023
TI  - Echocardiographic findings in patients with Wegener granulomatosis.
AB  - OBJECTIVE: To describe the spectrum and clinical implications of
      echocardiographic findings associated with Wegener granulomatosis. PATIENTS AND
      METHODS: We retrospectively reviewed the clinical records and echocardiographic
      data of consecutive patients with confirmed Wegener granulomatosis referred to
      the echocardiography laboratory during the 21-year period from 1976 through 1997.
      RESULTS: Of the 85 patients Identified as having confirmed Wegener
      granulomatosis, 73 (86%) were found to have echocardiographic abnormalities. In
      26 (36%) of these 73 patients, lesions appeared directly related to Wegener
      granulomatosis. We found regional wall motion abnormalities in 17 (65%) of these
      26 patients. Left ventricular systolic dysfunction with decreased ejection
      fraction was found in 13 patients (50%) and pericardial effusion in 5 patients
      (19%). Other findings Included valvulitis, left ventricular aneurysm, and a large
      intracardlac mass. A significantly increased mortality rate was observed among
      patients who had cardiac involvement of Wegener granulomatosis found by
      echocardiography. CONCLUSIONS: We found a high frequency of echocardiographic
      abnormalities that appear to be related to Wegener granulomatosis and associated
      with Increased mortality. Because cardiac involvement in Wegener granulomatosis
      often is silent and associated with Increased morbidity and worse prognosis,
      echocardlographic screening of patients with active Wegener granulomatosis may be
      of clinical value.

PMID- 16295024
TI  - Teaching cardiac auscultation: effectiveness of a patient-centered teaching
      conference on improving cardiac auscultatory skills.
AB  - OBJECTIVES: To assess the cardiac auscultatory skills of health care
      professionals before and after an actual (not simulated) patient-centered cardiac
      auscultation conference and to determine the effectiveness of this clinical
      teaching method on Improving diagnostic proficiency. SUBJECTS AND METHODS:
      Seventy-eight participants at a conference on cardiac auscultation completed
      preconference and postconference examinations on their ability to diagnose a wide
      variety of heart sounds and murmurs. Among those tested, 46 (59%) were
      physicians: 17 (22%) were cardiologists, 19 (24%) were medical Interns or
      residents, 7 (9%) were cardiology fellows, 2 (3%) were general practitioners, and
      1 (1%) was a pediatrician. Thirty-two (41%) of this group of respondents were
      nonphysicians: 14 (18%) were nurse practitioners, 9 (12%) were nurses, 6 (8%)
      were physician assistants, 2 (3%) were medical students, and 1 (1%) was a
      nonmedical professional. All participants were tested on 14 clinically Important
      cardiac auscultatory events directly recorded from actual (not simulated)
      patients and transmitted via wireless Infrared stethophones. The auscultatory
      events tested were wide physiologic splitting of S2 in right bundle branch block,
      fixed S2 splitting and systolic murmur in atrial septal defect, midsystolic click
      and late systolic murmur of mitral valve prolapse, S4 gallop, S3 gallop, opening
      snap of mitral stenosis, innocent systolic murmur, systolic murmur of mitral
      regurgitation, systolic murmur of tricuspid regurgitation, systolic murmur of
      hypertrophic obstructive cardiomyopathy, continuous murmur of patent ductus
      arteriosus, pericardial friction rub, prosthetic valve sounds, and alternation of
      heart sounds, heart murmurs, and the S3 gallop in congestive heart failure.
      RESULTS: On the basis of the analysis of the 78 participants who completed
      preconference and postconference evaluations of the 14 selected cardiac
      auscultatory events, a preconference Identification score of 26.3% and a
      postconference score of 44.7% were observed. This represents a statistically
      significant overall Improvement in diagnostic proficiency (P < .001).
      CONCLUSIONS: Cardiac auscultatory skills among today's health care professionals
      are extremely poor, regardless of the level and/or type of training of the
      professional. An actual (not simulated) patient-centered teaching conference is
      an effective clinical method of improving cardiac auscultatory skills and
      diagnostic proficiency of health care professionals.

PMID- 16295025
TI  - The Terri Schiavo saga: the making of a tragedy and lessons learned.
AB  - The recent case of Terri Schiavo has been an important medical, legal, and
      ethical controversy. However, much of the public discussion of the tragedy has
      been based on inaccurate information regarding the facts of the case and the
      actual legal and ethical issues involved. This article reviews the pertinent
      aspects of the case and the ethical and legal questions raised and highlights the
      lessons we should learn from this unique story.

PMID- 16295022
TI  - Celiac disease in type 1 diabetes mellitus in a North American community:
      prevalence, serologic screening, and clinical features.
AB  - OBJECTIVES: To estimate the prevalence of cellac disease (CD) in pediatric and
      adult type 1 diabetes melitus in a defined population and to describe clinical
      features and HLA class II genotypes predictive of CD in screened patients with
      type 1 diabetes. PATIENTS AND METHODS: All residents of Olmsted County,
      Minnesota, with type 1 diabetes mellitus on the prevalence date January 1, 2001,
      were identified with the use of an established medical records linkage system
      (Rochester Epidemiology Project) and defined clinical criteria. Consenting
      patients underwent serologic screening with endomyslal antibody and tissue
      transglutaminase antibody testing and Intestinal biopsies to confirm the
      diagnosis of CD. A subset of screened patients also underwent HLA class II
      genotyping. Quality-of-life screening (Medical Outcomes Study 36-Item Short-Form
      Health Survey) was completed in a subset of patients at the time of serologic
      screening. RESULTS: Overall, 392 Olmsted County residents with type 1 diabetes on
      January 1, 2001, were Identified. A total of 158 patients with type 1 diabetes
      were tested, representing 40% (158/392) of the enumerated diabetic population,
      and 11 had biopsy-proven CD for an estimated point prevalence of 7.0% (95%
      confidence Interval, 3.5%-12.1%). Most CD-positive diabetic patients were
      asymptomatic and expressed an at-risk CD haplotype with at least one of but not
      both HLA DQ2 or DQ8. CONCLUSIONS: Celiac disease Is not rare In North American
      patients with type 1 diabetes, and most CD-positive diabetic patients are
      asymptomatic Irrespective of age at screening.

PMID- 16295026
TI  - Medical and ethical aspects of long-term enteral tube feeding.
AB  - Clinicians frequently care for patients in whom long-term enteral tube feeding is
      being considered. The substantial increase in the use of endoscopically placed
      tubes for long-term feeding reflects the aging population, advances in medicine
      and technology, and inadequate advance care planning. Physicians should address
      advance care planning with all patients at the earliest opportunity. Prospective
      randomized trials measuring clinical outcomes for patients receiving long-term
      tube feeding are understandably limited. In addition, confusion regarding medical
      and ethical guidelines for long-term tube feeding often exists among clinicians,
      patients, and surrogate decision makers. Therefore, we discuss the physiology and
      clinical tolerance of limited oral nutritional intake, the prevalence of and
      Indications for long-term tube feeding, the endoscopic procedures and their
      complications, the reported medical and quality-of-life outcomes, and the
      critical importance of advance care planning. We present our multidisciplinary
      approach that combines medical, nutritional, and ethical principles for the care
      of these patients.

PMID- 16295027
TI  - Breast cancer-related lymphedema.
AB  - Every year in the United States, breast cancer is diagnosed in more than 200,000
      women. Because of the prevalence of breast cancer, treatment-related sequelae are
      of Importance to many survivors of the disease. One such sequela is upper
      extremity lymphedema, which occurs when fluid accumulates in the Interstitial
      space and causes enlargement and usually a feeling of heaviness in the limb.
      Axillary surgery contributes considerably to the incidence of lymphedema, with
      the incidence and severity of swelling related to the number of lymph nodes
      removed. Lymphedema after standard axillary lymph node dissection can occur in up
      to approximately 50% of patients. However, the risk of lymphedema is decreased
      substantially with newer sentinel lymph node sampling procedures. Adjuvant
      radiotherapy to the breast or lymph nodes increases the risk of lymphedema, which
      has been reported in 9% to 40% of these patients. Management of lymphedema
      requires a multidisciplinary approach to minimize the effect on the patient's
      quality of life. This review presents an overview of the pathophysiology,
      diagnosis, prevention, and treatment of breast cancer-related lymphedema.

PMID- 16295028
TI  - Hemophilia: a practical approach to genetic testing.
AB  - Hemophilia and von Willebrand disease together account for the large majority of
      congenital bleeding disorders. Contemporary management, including development of
      safer clotting factor concentrates and increased emphasis on long-term follow-up
      in comprehensive hemophilia centers, has improved both quality of life and
      longevity for patients with congenital bleeding disorders. In addition to
      facilitating development of recombinant clotting factor concentrates, isolation
      and characterization of the respective genes have led to increasing availability
      of a repertoire of genetic tests that, although expensive, are critical for
      appropriate genetic counseling of affected patients and their family members.
      This article provides a practical approach to using genetic testing for
      hemophilia A and B.

PMID- 16295029
TI  - Erythema Ab Igne from prolonged use of a heating pad.

PMID- 16295030
TI  - Influence of recent advances in medical management on clinical outcomes of
      cirrhosis.
AB  - Cirrhosis and its disease-related complications are the 12th leading cause of
      mortality among U.S. adults and are the 5th leading cause of death for
      individuals aged 45 to 54 years. Hospitalization costs for disease-related
      complications are estimated at 18,000 dollars per episode of care, and 10% of
      admitted patients die. Despite these ominous findings, the survival rate of
      patients with cirrhosis has improved during the past 2 decades. This observation
      coincides with the conducting and reporting of high-quality randomized controlled
      trials and observational studies. Therefore, the improved prognosis in cirrhosis
      may be related to the effective translation of research findings to clinical
      practice for this patient population. Although explicit data to support this
      claim are not available, this article reviews the reported trends in clinical
      outcomes for patients with cirrhosis and the existence of evidence-based medical
      information that is available to care for these chronically ill patients.

PMID- 16295031
TI  - 67-year-old man with fever, back pain, and lower extremity weakness.

PMID- 16295032
TI  - Solitary pulmonary metastasis presenting 20 years after primary resection of
      Wilms tumor.
AB  - Wilms tumor is the most common renal malignancy of childhood. Relapse occurs most
      often within 4 years of initial diagnosis, and the most common site of metastasis
      is the lung. We describe a 22-year-old man who presented with hemoptysis and a
      solitary pulmonary lesion 20 years after primary resection of Wilms tumor.
      Computed tomography of the chest showed an indeterminate pulmonary mass of
      heterogeneous attenuation with no other intrathoracic abnormalities. Surgical
      resection revealed a solitary pulmonary metastasis from Wilms tumor. Further
      evaluation yielded no evidence of extrathoracic metastases. This case shows that
      late relapse in the form of a solitary pulmonary mass can occur in patients with
      Wilms tumor.

PMID- 16295033
TI  - Adult acute lymphoblastic leukemia.
AB  - Much progress has been made in understanding the biology of and therapy for acute
      lymphoblastic leukemia (ALL). This progress has translated into the recognition
      of several subgroups of ALL and the institution of risk-adapted therapies. New
      therapies are emerging based on the definition of specific cytogenetic-molecular
      abnormalities. Changes in the pathologic classification of ALL have led to
      therapeutic consequences. Adaptation of successful treatment strategies in
      children with ALL has resulted in similar complete remission rates in adults.
      Prognosis has Improved especially in mature B-cell ALL and T-cell lineage ALL.
      However, regardless of ALL subgroup, long-term survival in adults is still
      inferior to that in children. Development of new drugs and agents tailored to
      subset-specific cytogenetic-molecular characteristics is vital to the therapeutic
      success in adult ALL.

PMID- 16295034
TI  - Surgical treatment of Zollinger-Ellison syndrome in multiple endocrine neoplasia,
      type 1.

PMID- 16295035
TI  - Complete heart block associated with mitral annular abscess.

PMID- 16295037
TI  - [Excimer laser (308 nm) - a new option in dermatologic UVB therapy].

PMID- 16295036
TI  - Mycobacterium avium complex olecranon bursitis in a patient treated with
      alefacept.

PMID- 16295038
TI  - [Immunopathogenesis of psoriasis].
AB  - Psoriasis is a chronic inflammatory disease of the skin and the joints. Multiple
      factors contribute to the initiation of psoriasis. They include specific genetic
      characteristics such as major histocompatibility antigens and psoriasis
      susceptibility genes, as well as trigger factors, namely streptococcal
      infections. Today, psoriasis is considered as a T-lymphocyte mediated autoimmune
      disease, even though the putative autoantigen remains unknown. Bacterial proteins
      with similarity to structural proteins of keratinocytes are potential target
      antigens. As in other autoimmune diseases, inflammatory cytokines of the innate
      immune system initiate a cascade that activates inflammation locally in the skin,
      in the circulation and most likely also in lymph nodes. IFN-gamma-producing CD4+
      Th1-lymphocytes seem to be of central importance in the pathogenesis of psoriasis
      as they critically influence differentiation and functioning of antigen
      presenting cells, mast cells, neutrophils and endothelial cells. This
      inflammatory cascade simultaneously provokes neoangiogenesis in the dermis and
      proliferation of keratinocytes. Based on this hypothesis, cytokines or
      anticytokine antibodies that either inhibit T-cell mediated inflammation or
      transform disease-inducing, pro-inflammatory Th1-lymphocytes into a phenotype
      with anti-inflammatory properties were tested in psoriasis. As both approaches
      improved psoriasis, they strongly support the current concept that views
      psoriasis as a Th1-lymphocyte mediated disease.

PMID- 16295039
TI  - [Treatment of acne with antiandrogens--an evidence-based review].
AB  - BACKGROUND: Increased sebaceous gland activity with seborrhea is one of the major
      pathogenetic factors in acne. Antiandrogen treatment targets the androgen
      metabolizing follicular keratinocytes and the sebaceous gland leading to
      sebostasis, with a reduction of the sebum secretion rate of 12.5-65%.
      Antiandrogens can be classified based on their mechanism of action as androgen
      receptor blockers, inhibitors of circulating androgens by affecting ovarian
      function (oral contraceptives), inhibitors of circulating androgens by affecting
      the pituitary (gonadotropin-releasing hormone agonists and dopamine agonists in
      hyperprolactinemia), inhibitors of adrenal function, and inhibitors of peripheral
      androgen metabolism (5alpha-reductase inhibitors, inhibitors of other enzymes).
      METHODS: All original and review publications on antiandrogen treatment of acne
      as monotherapy or in combination included in the MedLine system were extracted by
      using the terms "acne", "seborrhea", "polycystic ovary syndrome", "hyperandrog",
      and "treatment" and classified according to their level of evidence. RESULTS: The
      combinations of cyproterone acetate (2 mg)/ethinyl estradiol (35 microg),
      drospirenone (3 mg)/ethinyl estradiol (30 microg), and desogestrel (25 microg)/
      ethinyl estradiol (40 microg) for 1 week followed by desogestrel (125
      microg)/ethinyl estradiol (30 microg) for 2 weeks showed the strongest anti-acne
      activity. Gestagens or estrogens as monotherapy, spironolactone, flutamide,
      gonadotropin-releasing hormone agonists, and inhibitors of peripheral androgen
      metabolism cannot be endorsed based on current knowledge. Low dose prednisolone
      is only effective in late-onset congenital adrenal hyperplasia and dopamine
      agonists only in hyperprolactinemia. Treatment with antiandrogens should only be
      considered if none of the contraindications exist. CONCLUSION: Antiandrogen
      treatment should be limited to female patients with additional signs of
      peripheral hyperandrogenism or hyperandrogenemia. In addition, women with late
      onset or recalcitrant acne who also desire contraception can be treated with
      antiandrogens as can those being treated with systemic isotretinoin. Antiandrogen
      treatment is not appropriate primary monotherapy for noninflammatory and mild
      inflammatory acne.

PMID- 16295040
TI  - [Efficacy of barrier creams in comparison to skin care products in dental
      laboratory technicians--a controlled trial].
AB  - BACKGROUND: Irritant contact dermatitis of the hands is very common in dental
      laboratory technicians due to frequent contact with various irritants. Barrier
      creams (HS) are often avoided because a tight grip of tools and small objects is
      necessary; furthermore dental objects must not be contaminated by HS. In this
      study the efficacy of HS applied during working hours was compared to skin care
      products (HP) applied only after work. METHOD: 2 popular commercial HS (HS-1, HS
      2) and 2 moisturizers containing urea and beeswax respectively (HP-1, HP-2) were
      evaluated in 5 laboratories by a total of 192 technicians. Every technician used
      one HS (several applications during working hours) and one HP applied at home at
      least once daily for 4 weeks each with a wash-out period of 2 weeks in between.
      The sequence HS-HP, HP-HS was randomized for every laboratory in two single blind
      cross over designs for both combinations (HS-1 with HP-1, HS-2 with HP-2). The
      technicians scored the products on a scale of efficacy (worse, none, good, very
      good). The skin condition was evaluated by a dermatologist at the beginning of
      the study, after 4, 6 and 10 weeks on a scale for erythema, infiltration,
      vesicles, fissures and scaling to produce a sum score. Furthermore,
      transepidermal water loss (TEWL) was measured on the back of the hand and on the
      ventral aspect of the forearm at the beginnung and the end of the 4 weeks
      application period. The quotient of these two parameters was used for statistical
      evaluation (covariance analysis). RESULTS: The assessment of either "good" or
      "very good" was as follows: HS-1 58%; HS-2 67%; HP-1 77%; HP-2 98%. Both HP,
      particularly HP-2, were judged superior to either HS. This was confirmed by the
      improvement of the skin condition (HS-1 35%; HS-2 44%; HP-1 55%; HP-2 56%).
      Statistical significance of the differences in TEWL data was clearly
      demonstrated: HP-1 better than HS-1 (p = 0.007); HP-2 better than HS-2 (p =
      0.03). The acceptance of the products was high. The majority was willing to
      continue its usage after the study (68 %-89 %). CONCLUSIONS: The results
      demonstrate that the use of after work moisturizers is highly beneficial and
      under the chosen study conditions even superior to barrier creams applied at
      work. This approach is more practical for many professions and may effectively
      reduce the frequency of irritant contact dermatitis.

PMID- 16295042
TI  - [Therapy-resistant disseminated verrucae in an atopic patient with cellular
      immunodeficiency--successful topical treatment with imiquimod].
AB  - A 42- year-old atopic patient had suffered from disseminated verrucae since he
      was 14 years old. He had been treated with various, often expensive
      immunomodulatory agents for a long time without appreciable success. Laboratory
      tests revealed a striking T-cell defect. Topical treatment with imiquimod (Aldara
      5% Cream) led to the regression of all verrucae.

PMID- 16295041
TI  - [The use of the 308 nm excimer laser for the treatment of psoriasis].
AB  - BACKGROUND AND OBJECTIVE: Standard phototherapy for psoriasis (311 nm UVB or
      photochemotherapy) exposes the non-affected skin to potentially damaging
      irradiation. The use of 308 nm XeCl excimer laser allows the selective
      irradiation of psoriatic lesions. We evaluated its therapeutic effectiveness.
      PATIENTS/METHODS: 28 patients with plaque stage psoriasis were involved in the
      study, 26 of them could be evaluated. In each patient a single plaque was chosen
      and then exposed to the laser irradiation thrice weekly. The initial dose was
      twice the MED (minimal erythema dose); the dosage was increased by one MED every
      second treatment. The usual dosages were 2-5 MED, while the cumulative UVB dosage
      was 3.6-15.2 J/cm2. 17 Patients were treated 6 times, while 11 were treated 10
      times. The Psoriasis Severity Index (PSI) was calculated for the individual
      plaque in order to assess the effectiveness of the therapy. The patients were
      followed regularly for 3 months following treatment, and then checked again at 1
      year. RESULTS: Most patients showed clear improvement. In 90% the PSI at the end
      of treatment was reduced by at least 50%; in 72% it was only 33% of the pre
      treatment value. The results between the patients receiving 6 and 10 treatments
      were similar. In 6 patients, the psoriatic lesion was still absent after 1 year,
      while in an additional 7, there had been long term improvement. The most common
      side effects were erythema and pruritus (100%), blisters (35%) and post
      inflammatory hyperpigmentation (80%). CONCLUSION: The use of the 308 nm excimer
      laser is effective for chronic localized psoriasis and may lead to long-lasting
      remissions.

PMID- 16295043
TI  - [Fluorescence diagnosis in dermatology].

PMID- 16295044
TI  - [Atrophic flaccid maculae on the trunk of a 75-year-old patient].

PMID- 16295045
TI  - [Atopic dermatitis. Version (17 July 2002 - modified final version)].

PMID- 16295046
TI  - Dietary palmitic acid influences LDL-mediated lymphocyte proliferation
      differently to other mono- and polyunsaturated fatty acids in rats.
AB  - Recent studies suggest that the biological effects of saturated fatty acids
      depend on the length of their chain. We compared the effect of diets containing
      different fatty acids on plasma lipids and lymphocyte proliferation in the
      presence of lovastatin and with increasing amounts of LDL. Lymphocytes from rats
      fed with a diet rich in palmitic acid had a greater lymphocyte proliferation
      capacity than those from rats fed with diets rich in oleic acid, linoleic acid,
      or fish oil. This effect was maintained when small amounts of polyunsaturatwed
      fatty acids (PUFA; sunflower oil) were added to the palmitic acid diet. LDL
      receptor activity, measured by the capacity of lovastatin to revert the
      inhibition of lymphocyte proliferation with increasing amounts of LDL in the
      medium, was greater in the rats fed with palmitic acid, and was similar to the
      other groups when small amounts of PUFA were added. All the groups had similar
      levels of plasma cholesterol, but the LDL levels were significantly lower in the
      group fed with palmitic acid plus PUFA. The highest HDL-cholesterol (HDLc) levels
      were found in the palmitic acid group and the lowest LDL-cholesterol (LDLc)/HDLc
      ratio in the palmitic acid plus PUFA group. These results suggest that diets rich
      in palmitic acid do not raise total cholesterol, but reduce LDLc or keep it
      normal, and raise HDLc levels. This effect may be partly due to an increase in
      LDL receptor activity. The inclusion of small amounts of PUFA in the diet rich in
      palmitic acid substantially modified the LDL receptor response in the
      lymphocytes, suggesting that the proportion of different families of dietary
      fatty acids may be more important than the individual amount of each in absolute
      terms to explain their effects on plasma lipids and lipoproteins.

PMID- 16295047
TI  - Effect of lercanidipine compared with ramipril on albumin excretion rate in
      hypertensive Type 2 diabetic patients with microalbuminuria: DIAL study (diabete,
      ipertensione, albuminuria, lercanidipina).
AB  - Microalbuminuria and hypertension are risk factors for diabetic nephropathy in
      Type 2 diabetic patients. Recent data suggest that blockade of the renin
      angiotensin system slows the progression of diabetic nephropathy; in contrast,
      the results on the renoprotective effect of calcium channel antagonists are
      conflicting. We evaluated the effectiveness of lercanidipine, in comparison with
      ramipril, on the reduction in albumin excretion rate (AER) and blood pressure in
      mild-to-moderate hypertensive patients with Type 2 diabetes and persistent
      microalbuminuria. A total of 277 patients were enrolled in a multicentric,
      randomized, double-blind, active-controlled, parallel-group trial; 180 were
      randomized to receive 10-20 mg/day of lercanidipine or 5-10 mg/day of ramipril
      and followed up for 9-12 months. The primary outcome was the change in AER from
      baseline. After 9-12 months of follow-up, a reduction in AER of -17.4+/-65
      microg/min (p<0.05) and -19.7+/-52.5 (p<0.05) in the lercanidipine and ramipril
      group, respectively, was observed, without differences between the groups. A
      significant reduction in systolic and diastolic blood pressure was observed in
      both the lercanidipine and ramipril-based treatment groups (p<0.0001 for both).
      This study demonstrated that treatment with lercanidipine 10-20 mg/day does not
      worsen albuminuria in microalbuminuric Type 2 diabetic patients with
      hypertension. Indeed, both lercanidipine and ramipril treatments resulted in a
      significant reduction in AER without a statistically significant difference
      between the two groups.

PMID- 16295048
TI  - Apolipoprotein E polymorphism in Turkish subjects with Type 2 diabetes mellitus:
      allele frequency and relation to serum lipid concentrations.
AB  - The role of apolipoprotein E (apoE) genotypes in modulating plasma lipid and
      apolipoprotein levels was studied in 112 patients with Type 2 diabetes mellitus
      (T2DM) and 94 healthy individuals. ApoE genotypes were identified by PCR
      amplification and subsequent restriction endonuclease digestion. The apoE allele
      and genotype frequencies were similar in both the diabetic and control subjects.
      The apoE allele frequencies were found to be 74.3 for e3, 10.1 for e2, 15.6 for
      e4 in the diabetic group, and 68.1 for e3, 13.2 for e2 and 18.7 for e4 in the
      control group. Sex-specific genotypic distribution of apoE polymorphism did not
      differ between the study groups. To elucidate the association of apoE with lipid
      abnormalities with respect to gender, serum lipid and apolipoprotein levels were
      compared among apo e2 (e2/2 and e3/2), e3 (e3/3) and e4 (e4/3 and e4/4) groups of
      T2DM and control subjects. Apo e2 allele was found to be associated to
      triglycerides for both sexes, and associated to glucose, and BMI only in females.
      Subjects with e2 allele had higher levels of BMI, glucose and triglyceride in
      comparison to e3 and e4. Our data suggest that genetic variation at the apoE
      locus in Turkish subjects is a genetic factor that influences lipid levels.
      Further studies attempting to correlate apoE polymorphism with lipid profile in a
      large number of individuals would be helpful in establishing the true
      significance of this polymorphism in the Turkish population.

PMID- 16295049
TI  - Glycemic optimization may reduce lipid peroxidation independent of weight and
      blood lipid changes in Type 2 diabetes mellitus.
AB  - The aim of this study was to determine the effect of diet-therapy on lipid
      peroxidation in patients with Type 2 diabetes mellitus (T2DM). Fifteen T2DM
      patients of both sexes, aged between 35-70 years, were given the diet suggested
      for patients with diabetes by the American Diabetic Association. This diet
      comprised 50-60% carbohydrate, 10-15% protein, 20-30% fat and about 35 g fiber
      was given for weight maintenance. Weight and body mass index did not change
      significantly during 8 weeks of study. Also, no statistically significant
      difference was observed in serum total cholesterol, triglycerides, LDL- and HDL
      cholesterol from before to after dietary intervention. However, the levels of
      fasting blood sugar, HbA1c and malondialdehyde were lowered significantly after
      dietary intervention. It was concluded that glycemic optimization, independent of
      weight and blood lipid profile, through a well-designed diet is likely to be the
      most effective factor in reducing the process of oxidative stress in T2DM. This
      may have preventive implications for such diabetic complications as
      atherosclerosis.

PMID- 16295050
TI  - Estimation of physical activity by different questionnaires in overweight
      subjects and patients with Type 2 diabetes mellitus: relationship with
      anthropometric and metabolic variables.
AB  - AIM: This study assessed the level of physical activity in overweight and obese
      subjects, and overweight and obese patients with Type 2 diabetes mellitus (T2DM).
      It also compared their physical activity level with that of the general
      population and investigated benefits of physical activity on anthropometric and
      metabolic parameters and blood pressure in the studied groups of patients using
      Baecke's questionnaire and the Lipid Research Clinics Physical Activity (LRC PA)
      questionnaire. The two questionnaires were also compared in the evaluation of
      benefits. METHODS: Physical activity level and other parameters (body weight,
      body height, body mass index, waist-to-hip ratio, systolic and diastolic blood
      pressure, lipoprotein and creatinine concentrations in the blood, concentration
      of fasting glucose and HbA1c in the blood, albuminuria-to-creatinuria ratio) of
      136 subjects and their relationships were investigated during their out-patient
      visits. RESULTS: No difference in physical activity level was found among the
      four groups of investigated patients. The comparison between the level of
      physical activity in the investigated patients and the general population
      obtained by Baecke's questionnaire revealed a lower sports index in all groups of
      investigated men and obese women with diabetes mellitus. Our results confirm the
      benefit of physical activity on a high number of investigated parameters in the
      studied patients. The Baecke's questionnaire was found to estimate the effects of
      physical activity on metabolic and anthropometric parameters, as well as blood
      pressure, better than the LRC PA questionnaire, especially the two-point scoring
      system. CONCLUSIONS: LRC PA and especially Baecke's questionnaires are valuable
      aids in the estimation of physical activity level and its benefits in overweight
      and obese patients and patients with T2DM.

PMID- 16295052
TI  - Prevalence of obstructive sleep apnoea in a sample of obese women: effect of
      menopause.
AB  - BACKGROUND: Obesity is a well known risk factor for obstructive sleep apnoea
      (OSA). Previous studies have investigated the prevalence of OSA among obese
      people, but a sample of women was rarely studied. OBJECTIVE: To describe the
      anthropometric and polysomnographic characteristics of a sample of obese women
      and investigate the effect of menopause on the prevalence of OSA. MATERIALS AND
      METHODS: Using a full-night polysomnography we studied a sample of 133 obese
      women with a body mass index (BMI) > or = 30 kg/m2. RESULTS: About 44% of our
      sample had a respiratory disturbance index (RDI) > or = 10. Neck circumference,
      BMI and age resulted the strongest predictors of RDI value. We also found that
      the prevalence of OSA was higher among post-menopausal women (67%) in comparison
      with pre-menopausal women (31%). Moreover, post-menopausal women had larger neck
      circumference and higher waist-to-hip circumference ratio (WHR). CONCLUSIONS:
      Among post-menopausal obese women the prevalence of OSA increases. We suggest
      that menopause could cause a different body fat distribution with an increase of
      fat in upper parts of the body and, consequently, with an increase of neck
      circumference.

PMID- 16295051
TI  - Associations among sex hormone binding globulin concentrations and
      characteristics of the metabolic syndrome in obese women.
AB  - The aim of this study was to determine sex hormone binding globulin (SHBG)
      concentrations in premenopausal obese women who were otherwise healthy, and to
      evaluate the relationships between SHBG concentrations and features of the
      metabolic syndrome; 307 premenopausal women (mean age 30.9+/-10.2 years) were
      studied. Subjects were divided into two groups according to the BMI: Group I,
      women with BMI <30 kg/m2 (n=69) and Group II, women with BMI > or = 30 kg/m2
      (n=238). Insulin resistance was determined according to the Homeostasis Model
      Assessment (HOMA) formula. Median SHBG concentration of Group I was 75.9 nmol/l.
      Group II was divided into two subgroups according to the median SHBG
      concentration of Group I; women with high SHBG (SHBG concentration > or = median
      level of the control group, i.e. > or = 76 nmol/l) and women with low SHBG (i.e.
      <76 nmol/l). The low SHBG group was significantly younger, with higher waist-to
      hip ratio (WHR). Triglycerides, uric acid, insulin and HOMA values were
      significantly higher and HDL-cholesterol was significantly lower in the low SHBG
      group. Multiple regression analysis revealed that age and uric acid
      concentrations were significant independent predictors of SHBG concentrations in
      the whole group (regression summary, adjusted r2=0.1414, F=10.5627, p<0.001). It
      is concluded that low SHBG concentrations may indicate a severe degree of insulin
      resistance in premenopausal obese women.

PMID- 16295054
TI  - Resting metabolic rate incremented by pulsating electrostatic field (PESF)
      therapy.
AB  - Pulsating electrostatic field (PESF) therapy was investigated to assess the
      possibility of increasing the resting metabolic rate (RMR) in 14 adult females.
      The pumping effect of positive calcium and hydrogen ions was obtained by 30 min
      daily exposure to negative PESF, adjusted individually between 2 and 9 kV. This
      treatment could result in a buffering effect on blood pH and reduction of the
      rouleaux formation of erythrocytes, thus ameliorating the oxygen exchange
      potential and the red cell circulation in the capillary system. After PESF
      therapy, the average RMR (measured by indirect calorimetry) of 1255 kcal was
      increased on average by 323 kilocalories, indicating a possible role of PESF in
      the obesity treatment.

PMID- 16295053
TI  - Effectiveness of an uninterrupted procedure to transfer adolescents with Type 1
      diabetes from the Paediatric to the Adult Clinic held in the same hospital: eight
      year experience with the Parma protocol.
AB  - This paper reports an 8-yr retrospective study on the effects of an uninterrupted
      procedure of transition of 73 adolescents with Type 1 diabetes from the
      Paediatric to the Adult Clinic held in the same hospital. Interviewed patients
      had a mean age of 21.0+/-0.95 yr at transition. Patients were satisfied with the
      information received before transition (100%), and appreciated being introduced
      to the adult physician prior to being transferred (92%), and having found their
      paediatrician during the first visit at the Adult Clinic (100%). Consensus for
      transition was attained after 2-4 consultations in 66.6% of patients. Seventy
      nine percent of patients considered 20 yr of age as an appropriate age to be
      transferred. Patients confirmed to have found at the Adult Clinic: privacy (85%),
      confidentiality (95%), short waiting times (78%), informal atmosphere (100%), and
      the same consultant (100%). Only 3% of patients tried to go back to the
      Paediatric Clinic but they were discouraged. Clinic attendance rate ranged
      between 92 and 100%. We consider that the key factors for a successful process of
      transition from a Paediatric to an Adult Clinic are: age at transfer around 20
      yr, smooth movement within the same hospital, consensus of patients and their
      parents, prior personal contact with the adult physician, paediatrician
      attendance at the first visit at the adult service and his unambiguous role
      against all attempts to go back to the paediatric service and, finally, the
      availability of the same physician at out-patient clinic visits.

PMID- 16295055
TI  - Metronidazole retention enema in the management of severe intestinal amoebiasis.
AB  - Metronidazole is a drug of proven efficacy in amoebiasis; however its use is
      restricted in patients who cannot take the drug by mouth, because of severe
      complications of the disease. Preliminary studies in eight control subjects show
      that rapid absorption and high serum levels are achieved after rectal
      administration of 2 gm. of metronidazole in 200 ml. of normal saline. Six
      patients with severe intestinal amoebiasis treated with metronidazole retention
      enema are presented, and they illustrate the efficacy of the new method of
      therapy. The efficacy of metronidazole in anaerobic bacteriodes infection and its
      proven amoebicidal effcet also indicate the possible use of the metronidazole
      retention enema technique in bowel preparation for colonic surgery in developing
      countries.

PMID- 16295057
TI  - Experience with urinary calculus disease in Nigerians as seen at the Lagos
      University Teaching Hospital.
AB  - The rarity of urinary calculus disease in this community was established by
      reviewing the cases seen in the Lagos University Teaching Hospital over an eleven
      year period and also by reviewing autopsy records of 5,022 patients. In the
      clinical review 45 stones were recorded in a period during which 636,735 Nigerian
      patients were seen in the clinics putting the incidence of stones in the urinary
      tract as 7 in 100,000. At the time the patients were seen, sixteen stones were
      located in the kidneys nine stones in the ureters, twenty two stones in the
      bladder and four in the urethra. Three patients had stones in multiple sites. In
      only nine patients (20%) were the stones idiopathic while the rest could be
      blamed on various forms of obstructive uropathy, stasis, infection or metabolic
      disorders. This contrasts sharply with stones in caucasians in which about 66%
      are idiopathic. Children and females were rarely affected by urinary stones. In
      the autopsy review, only two adult were found to have stones out of a total of
      5,022 bodies. Although urinary calculi may be silent and remain undiagnosed, this
      low autopsy incidence indicates that stones are not just being missed in the
      clinics but that it is uncommon in this community.

PMID- 16295056
TI  - The immunobiotherapy of cancer: a preliminary report of a study of leucocytes
      cultured with B. C. G. or tuberculine on malignant disease.
AB  - When leucocytes from normal young adults were cultured with BCG or tuberculine,
      in vitro, lymphoblasts were observed in the cultures. Such cultures, especially
      the cell free supernatant, when injected into 2 patients with recurrent thyroid
      carcinoma and rhabdomyosarcoma respectively, repeatedly caused necrosis of these
      tumour. Although the nature of the substance responsible for the necrosis is at
      present unknown, it was very potent, and non antigenic and probably of small
      molecular weight as it killed the tumour cells by diffusing to them in the tissue
      fluid. The patients who received the infusion were not cured of their tumours but
      the method holds promise for palliating and even possibly treating patients with
      advanced cancers not suitable for other forms of treatment. It could also be used
      in place of BCG vaccination in Hodgkins disease, leukaemias and other
      lymphoreticular tumours with a weakened or incompetent cell mediated immune
      system-CMIS. This study provides further support for recommending regular BCG
      vaccination of normal people as a prophylaxis against cancer.

PMID- 16295058
TI  - Effect of a mixture of red pepper (Capsicum frutescens) and an amino-acid on
      gastric acid secretion.
AB  - The effects of a mixture of red pepper suspension and alpha-alanine (an amino
      acid) on gastric acid secretion in 33 duodenal ulcer and 18 non-duodenal ulcer
      patients were studied. This mixture caused an increase of gastric acid in the two
      groups of patients, more so in the duodenal ulcer group (0.025 > P > 0.010).
      Compared with the results of previous studies the administration of alpha-alanine
      in red pepper suspension produced less gastric acid than the fresh red pepper
      suspension alone.

PMID- 16295059
TI  - Post-operative deep vein thrombosis incidence in Nigerians.
AB  - In 450 consecutive Nigerian patients aged 20 and above undergoing elective
      surgery, the incidence of post-operative deep vein thrombosis using clinical
      methods was 2.2 per cent. Of these 333 were men and 5 had deep vein thrombosis
      giving an incidence of 1.5 per cent while 117 were females and 5 had deep
      thrombosis giving an incidence of 4.3 per cent. This figure is low and appears to
      agree with the current opinion that post operative deep vein thrombosis is
      comparatively rare in Africans. This is in contrast to the view expressed by
      Nwokolo and Ikoku (1967) that thromboembolic disease is more common in Nigeria
      than in East and Central Africa.

PMID- 16295060
TI  - A radical approach to management of external hernias in Nigeria.
AB  - This is a review of 552 cases of hernias treated at the Adeoyo State Hospital
      Ibadan between January 1968 and October 1970. It highlights the significance of
      the use of local anaesthesia in the surgery of hernias, particularly those
      managed on outpatient basis. This method is of importance to doctors working
      single-handed in district hospitals in this country. It deals with the common
      complications and the management of these. It draws attention to the relative
      frequency of femoral hernias in men in Western Nigeria and Lagos. It also shows
      that mortality from complications is due mostly to late reporting which can be
      prevented by better health education of the population.

PMID- 16295061
TI  - Management of male infertility.

PMID- 16295062
TI  - Aerosol beclomethasone in steroid dependent asthmatics.
AB  - Aerosol beclomethasone dipropionate was effective in maintaining airway patency
      in 14 out of 16 steroid-dependent asthmatics. In 3 patients who had significant
      adrenal suppression on systemic corticosteroid therapy substitution with aerosol
      beclomethasone led to recovery of adrenal function. From the evidence obtained it
      is concluded that this aerosol steroid represents a modest advance in the therapy
      of asthma.

PMID- 16295064
TI  - The incidence of hepatitis B antigen in blood donors in Port Harcourt.
AB  - The Sera of 887 asymtomatic volunteer donors were subjected to a
      haemagglutination screening technique (Hepanosticon Test) for the detection of
      Australian B Antigen (HBAg). Forty-one of these Sera were strongly positive and
      two were positive giving an incidence 4.6% which is higher than previously
      reported incidence. The implication of these findings is discussed.

PMID- 16295063
TI  - Yellow fever outbreak in South Eastern State of Nigeria--virological and
      serological studies.
AB  - An outbreak of Yellow Fever in South Eastern State involving Uyo, Itu and Abak
      divisions is presented. The occurrence of few jaundiced cases with fever in
      places 29-35 km outside Uyo indicated that the epidemic was more widely spread
      than it was thought. The rural communities appeared to be more severely affected
      where a considerably large number of unrecorded deaths were reported. Mortality
      rate was about 56% among hospitalised patients. The diagnosis of Yellow Fever was
      confirmed by virus isolation and serology This was the first recorded outbreak in
      this area.

PMID- 16295065
TI  - Hereditary spherocytosis in Nigerians.
AB  - Five cases of hereditary spherocytosis in Nigerians are discussed. The clinical
      presentation and haematological abnormalities are similar to those described in
      other parts of the world. In one patient family studies were negative. The series
      does not permit a gene frequency estimate for the country but the cases came from
      widely separated area, suggesting that no ethnic group has more predilection than
      others. Splenectomy was uniformly successful.

PMID- 16295066
TI  - A survey of haematological variables in 600 healthy Nigerians.
AB  - 625 healthy Nigerians were studied for investigation of Haemoglobin
      concentration, leucocyte count, Erythrocyte sedimentation rate, Blood group and
      haemoglobin genotype. Haemoglobin levelin healthy adult Nigerians are Males 13.5
      gm%, Female 11.3 gm%. There is no change in the haemoglobin level with storage
      and no difference in females studied in pre and post mentrual stages. These
      figures are lower than for Europeans. The white blood count for adult males is
      mostly in the range 2,000-5,000 cells/cmm and adult female range 5,000-8,000
      cells/cmm. There is a reduction in the leucocyte count with storage. These
      figures are again lower than for Europeans. Erythrocyte sedimentation rate in
      males is mostly 0-3 mm/hr Westergren for males and 10-20 mm/hr for women. The ABO
      Blood group is distributed differently from that in Europeans and is Gp 0-53.5%
      Gp A-27%, Gp B 17.5% Gp AB-4%. Haemoglobin Genotypes are AA-77.5% AS19.6%; AC
      0.8%; CC-0.8%; SC-0.8%; SS-0.4%.

PMID- 16295067
TI  - Preliminary report on measurement of immunoglobulin IgG in Nigerian patients with
      dermatomyphytosis.
AB  - Thirty non-atopic adult Nigerian patients, with dermatophytosis, who showed no
      other demonstrable abnormality, and who denied any family history of atopy were
      studied for serum levels of immunoglobulin IgG. The results of serum gamma G.
      Immunoglobulin concentrations, as measured by the formation of precipitant rings
      using the Hyland technique in these patients, when compared with those in two
      control subjects and three other patients with trichophytide reactions, clearly
      showed much higher concentrations of IgG class of immunoglobulin in
      dermatophytosis. This finding thus supports an immunological role, as has been
      postulated by other investigators, in the pathogenosis of this disease. The high
      levels of this immunoglobulin in some of these patients calls for further study.
      Possible hypotheses are given. The serum levels of IgE levels of patients with
      "Ide Reaction" needs to be measured. The Hyland Immunoplate technique method of
      quantitation of immunoglobulins is described. The practising allergist can now
      measure most immunoglobulins.

PMID- 16295068
TI  - Experiences with neuroleptanalgesia in Ibadan.
AB  - A study of the usefulness of neuroleptanalgesia is presented. It was found
      satisfactory as the sole anaesthetic technique for procedures not lasting longer
      than 30 minutes. Very painful procedures may require supplementation with another
      anaesthetic agent. Cardiovascular stability, excellent psychomotor sedation and
      patient co-operation are some of its advantages. Respiratory depression occurs if
      the Fentanyl is injected i.v. too fast, but this is reversible. The drugs are
      also useful for premedication and anaesthesia in poor risk patients. Some
      precautions for its use are suggested.

PMID- 16295069
TI  - Birthweights of Nigerian children.
AB  - A retrospective study of birthweights, the incidence, and possible aetiology of
      low birthweight in 31,490 Nigerian children, delivered in two hospitals at
      Ibadan, is reported. The important findings were: (a) mean birthweights for males
      (3,000 gm), and for females (2,880 gm) in a non-teaching hospital were
      significantly higher than 2,980 gm and 2,860 gm for males and females
      respectively in the teaching hospital; (b) the mean birthweights for boys were
      significantly higher than those for girls in both hospitals; (c) these mean
      birthweights, though generally higher than previous reports from Nigeria, were
      significantly lower than those for North American Caucasian and Negro babies, and
      of babies of three different racial groups in Malaysia. Other interesting, though
      expected findings were: (a) a high incidence of low birthweight (15.5 per cent)
      and (b) a high incidence of small for dates babies (60 per cent). It is suggested
      that since birthweights, the incidence of low birthweight and its aetiology are
      vital in the planning of health care in any country, a prospective study
      involving many urban and rural areas of the country and including factors known
      to influence birthweight should be undertaken.

PMID- 16295070
TI  - Analysis of paediatric medical cases admitted to Children's Clinic Benin City.
AB  - Until the Paediatric Ward at the University of Benin Teaching Hospital was
      commissioned in August, 1973, the Children's Clinic of the Specialist Hospital,
      Benin City was the only unit for specialised treatment of sick children. From
      June 1972 when the Clinic was opened to May 1973 (12 month period)--56,000
      children aged from a few days to 15 years were treated. 4720 (8.5%) of the total
      seen were admitted and 212 (4.5%) of total admission died. The average age for
      both children admitted and those who died was 2 years. While the average for in
      patient care was 4 days, that for children who died was 2 days. So called
      tropical diseases except malarial infection and sickle cell anaemia were not
      common. The three commonest diagnoses were Enteritis, Respiratory infections and
      malaria.

PMID- 16295071
TI  - Evaluating retrograde hysterectomy in the surgery of pelvic gynaecologic diseases
      in Nigeria.
AB  - A modified technique of total abdominal hysterectomy in the presence of gross
      distortion of pelvic anatomy with displacement of vital structures by chronic
      pelvic inflammatory disease with or without tubo-ovarian abscess formation and
      adherent giant myomas of the uterus is described. In the 16 cases personally
      operated upon by the author there were no major operative or post-operative
      complications. Experience with this procedure is reviewed and its wider use
      advocated. The removal of the uterus and adnexa by the abdominal route is one of
      the commonest procedures in gynaecological practice. The technique is fairly well
      standardized and is a relatively simple operation provided that the surgeon has a
      thorough knowledge of the anatomy of the pelvic organs. In our practice at
      Ibadan, it is fair to say that the uterus of normal size and mobility to which
      most textbook descriptions of technique apply forms a minority of the cases
      presenting for total abdominal hysterectomy. Experience has shown that there is a
      high incidence of chronic pelvic inflammatory disease with or without tubo
      ovarian abscess formation, adherent giant myomas of the uterus, cervical and
      intra-ligamentous fibroids and cysts and enlarged adherent benign ovarian tumours
      in the community. These may cause distortion of pelvic anatomy with displacement
      of the ureters, bladder, colon and rectum from their normal position. Experience
      has shown that urinary tract and colonic injuries may occur at operation when the
      pelvic anatomy is grossly distorted making true anatomical dissection often
      impracticable. Operative treatment can be very difficult in these instances and
      success depends on correct surgical technique with suitable instruments and
      personal experience, the necessary versatality and skill developed with practice.
      Various techniques for abdominal hysterectomy have been developed and reported
      (Richardson, 1929; Farrar, 1935; Aldrige, and Meredith 1950; Gray, 1958; Murless,
      1963; Cabaniss, and Gill, 1964). The technique to be described was originally
      developed by Bonny (Macleod and Howkins 1964) except for minor modifications and
      has been used exclusively by the author in the last three years in selected cases
      with gross pelvic anatomic distortion where the conventional method of abdominal
      hysterectomy is impracticable. This improved surgical technique has decreased the
      hazards of pelvic surgery tremendously in difficult hysterectomies in my
      practice.

PMID- 16295072
TI  - A review of patients admitted to the female psychiatric ward of a University
      College Hospital in Nigeria.
AB  - A review of patients admitted to a six bedded female psychiatric ward of the
      University College Hospital, Ibadan, Nigeria over a seven year period is
      presented. 391 patients (accounting for 469 admissions) were admitted to the ward
      during the period under review. Young persons, those who had ever been married,
      and Christians predominated in the cohort. Although, the hospital serves the
      whole country, a majority of the patients came from the Region in which the
      hospital is situated and most of the patients were admitted from the outpatient
      clinics of the hospital. Psychosis formed the largest diagnostic category with
      schizophrenia predominating in this group. Paranoid symptoms were common. Sixty
      three percent of the patients were discharged within one month of admission with
      only 6% spending longer than 60 days in the ward. 85% were assessed as having
      improved on discharge. There was a high defaulter rate at the follow-up clinics.

PMID- 16295073
TI  - Pattern of tooth loss in Nigerians.
AB  - 3,168 patients seeking treatment between November 1973 and March 1974 were
      studied in the Oral Diagnosis and Treatment Planning Unit of the Department of
      Preventive Dentistry. 31.94% of this study group were recommended for teeth
      extraction. Of those recommended for teeth extraction, the highest incidence
      (45.54%) was in the 7-12 years old group, and the lowest incidence (27.11%) was
      recorded in the group above 18 years. In the group up to six years old, there was
      a high percentage of loss of the deciduous molars especially the lowers (53.65%
      of males) and 44% of females. In the older groups there was also a high % loss of
      succidaneous molars particularly the lowers. The figures recorded are as follows:
      In the 7-12 years old 36.6% of males and 20.23% of females. In the 13-18 years
      old 61.3% of males and 69.29% of females. In the group above 18 years 34% of
      males and 44% of females. These figures show that contrary to general belief,
      Africans do not invariably keep their teeth perpetually. It has been shown that
      the incidence of Dental disease is rising. Although the demand for treatment is
      also increasing, there is shortage of manpower to prevent the high loss of teeth.
      With these facts in mind, it is our belief that ,efforts at preventive measures
      should be increased.

PMID- 16295074
TI  - Ossifying (odontogenic) fibroma of the maxilla. A case report.
AB  - A case of grossly disfiguring ossifying fibroma of the left maxilla is presented.
      The lesion expanded the left maxilla, the left zygomatic bone and it filled the
      left maxillary antrum to the partial obstruction of the nares. The lesion was
      completely excised under general anesthesia. About a year post-operatively,
      patient was fitted with a denture obturator. Further cosmetic osteotomy
      contemplated on the zyomatic bone which was flayered out could not be carried out
      because the patient was lost to follow-up.

PMID- 16295075
TI  - The roentgen diagnosis of a case of Takayasu's Arteriopathy.
AB  - Arteriography is of major importance in the diagnosis of Takayasu's arteriopathy.
      It reveals that: (a) The disease is localized to the larger arteries near their
      origin, and in this case the subclavian arteries. (b) Occlusion of both
      subclavian arteries is demonstrated. (c) There is present a well developed
      collateral circulation, with rib notching due to dilated intercostal arteries.
      The patient will be followed up to watch the progression of the disease.

PMID- 16295076
TI  - Angioneurotic oedema. A case report.
AB  - The present paper reports a case of angioneurotic oedema following application of
      a hair dye in a lady with no previous history of atopy. The literature on the
      disorder has been reviewed.

PMID- 16295077
TI  - Myocardial disease in Nigerians.
AB  - The problem of heart disease of unknown aetiology as it is found in the Nigerian
      environment is presented. The fact that it is nearly impossible on many occasions
      to make a conclusive diagnosis on clinical grounds alone of either endomyocardial
      fibrosis and heart muscle disease is discussed and the need for haemodynamic and
      angiographic studies to make the differentiation is stressed. The clinical,
      radiological, electrocardiographic, and haemodynamic features of each of the two
      varieties of "cardiomyopathy" is presented and the distinguishing features are
      emphasised. The occasional difficulty in differentiating heart muscle disease
      from hypertensive heart disease is discussed and the fact that the two differ
      distinctly on haemodynamic pressure studies is established. Previous published
      hypotheses regarding the aetiology of these cardiac conditions are discussed, and
      suggestions are made as to the lines of future research including virological
      studies and the possible myocardiopathic effect of some of the local traditional
      herbs.

PMID- 16295079
TI  - Towards improving the administrative machinery for health care in the Midwestern
      State of Nigeria.
AB  - The paper discusses the present machinery for the administration of health care
      facilities in the Midwestern State of Nigeria and makes suggestions for
      improvement. The multiplicity of autonomous authorities involved in the running
      of health care facilities and the compartmentalization of health care into
      'preventive' aspects (managed by the State Ministry of Health and Local
      Authorities) and 'curative' aspects (managed by the State Hospitals Management
      Board) are seen as the main disadvantages of the present system. A new
      administrative set-up is suggested, the highlights of which include the creation
      of a number of Area Health Boards that will have responsibility for all State
      Government and Local Authority health care facilities in their respective
      geographically defined areas of jurisdiction (this will abolish the artificial
      division between the administrations of 'preventive' and 'curative' aspects of
      health care), more professional divisions in the state Ministry of Health (which
      will retain responsibility on behalf of government for policy matters and the
      provision of health care facilities) than at the moment, a State Health Service
      Commission and A State Health Advisory Committee. It is important for doctors and
      other personnel in the health care field to know something about the
      administrative machinery of the health care delivery system in which they work.
      Apart from doctors who are trained in certain postgraduate fields, most other
      doctors do not appear to have any formal training in or early exposure to medical
      administration and yet, some of them get called upon during their career to
      undertake administrative duties at a very high level. This paper describes the
      present system of administration of health care facilities in the Midwestern
      State and offers suggestions for consideration for improvement. It is a well
      known fact that the administration of health care facilities in the Midwestern
      State has improved considerably in recent years. The suggestions in this paper
      are offered in the belief that they will stimulate discussion and eventually
      contribute towards further improving the administrative machinery for health care
      delivery in the State. The geographical entity now known as the Midwestern State
      was earlier known as the Midwest Region from 1963 until 1967 when it became the
      Midwestern State. It occupies an area of about 15,000 sq. miles, has a population
      of nearly three million people and is divided into fourteen administrative
      divisions.

PMID- 16295078
TI  - Role of the anaesthetist in the prevention of maternal deaths in Caesarian
      Section.
AB  - The obstetric anaesthetist should not only be skilled in the administration of
      anaesthesia, but should also have a thorough knowledge of the pharmacology and
      physiology of pregnancy, labour and delivery and the full implications of the
      complications that may arise in late pregnancy and during labour. The diagnosis
      and treatment of these complications are as much his concern as the choice and
      administration of anaesthetic agents. Such complications which may arise before,
      during and after Ceasarian Section include prolonged and obstructed labour,
      inhalation of gastric contents, pre-eclamptic toxaemia and eclampsia, haemorrhage
      and coagulation disorders, supine hypotensive syndrome and amniotic fluid
      embolism. Close co-operation between obstetrician and anaesthetist, careful
      overall management and the judicious choice of drugs in pre-medication,
      anaesthetic agents and techniques, on the lines outlined and discussed should aid
      the reduction of meternal mortality in elective and emergency caesarian section
      to the barest minimum.

PMID- 16295080
TI  - First in black Africa.

PMID- 16295081
TI  - Hereditary renal diseases.

PMID- 16295082
TI  - Cryoglobulinemia in thalassemia major: a preliminary report.

PMID- 16295083
TI  - Giemsa banding patterns of 13/14, 21/21 translocations, Philadelphia chromosome
      and trisomy 18.

PMID- 16295084
TI  - A study of the etiology and prognosis of breath-holding spells.

PMID- 16295085
TI  - Larsen's syndrome.

PMID- 16295087
TI  - Erythropoietin in children I. Findings in Hodgkin's Disease.

PMID- 16295086
TI  - Pycnodysostosis.

PMID- 16295088
TI  - The heritability of liability to Talipes equinovarus and genetic counseling.

PMID- 16295089
TI  - Serum Mg, Ca, total protein levels in maternal and cord blood and its clinical
      significance.

PMID- 16295090
TI  - The heritability of liability to congenital dislocation of the hip.

PMID- 16295091
TI  - Partial lipodystrophy with renal disorder.

PMID- 16295092
TI  - An unusual case of gastric carcinoid with metastases.

PMID- 16295093
TI  - Handedness and the retention of visual material.

PMID- 16295094
TI  - Effects of task requirements on ear superiority for sung speech.

PMID- 16295095
TI  - Recognition memory after head injury: a signal detection analysis.

PMID- 16295096
TI  - On frontal lobe functions: psychiatric patient controls.

PMID- 16295097
TI  - Visual, tactile and acoustic embedded figures tests in patients with unilateral
      brain damage.

PMID- 16295098
TI  - Verbal comprehension in aphasia: an English version of three Italian tests.

PMID- 16295099
TI  - The absence of covert verbal mediation in aphasia.

PMID- 16295100
TI  - Dichotic ear-order effects with nonverbal stimuli.

PMID- 16295102
TI  - Apraxia and agraphia in a right-hander.

PMID- 16295101
TI  - An investigation of writing therapy for the adult aphasic: the world level.

PMID- 16295103
TI  - Deficient recognition memory in organic amnesia.

PMID- 16295104
TI  - The development of the lateral functions and reading ability.
AB  - This study demonstrates a relationship between the development of two progressive
      processes: (1) language function in the brain, and (2) reading ability. The data
      suggest that different degrees of hemispheric asymmetry for speech appear to be
      advantageous as the various phases of reading are approached. The progression of
      laterality appears to be from little asymmetry between the right and left ears
      (ambilaterality) in the earliest learning-to-read stages (at 5, 6 and 7 years of
      age) when both sides of the brain are necessary for the vast amount of visual
      spatial as well as linguistic information which must be processed, to a maximum
      asymmetry in the later, fluent reading stage (in those 8 years and older) when
      the language side of the brain, usually the left, appears to be specialized for
      this skill.

PMID- 16295105
TI  - Digit repetition performance in patients with focal brain damage.
AB  - Digit span forward and backward was investigated in well-matched samples of
      patients with discrete quadrant brain lesions. The incidence of significantly
      impaired digit repetition performance and the incidence of large forward and
      backward digit span discrepancies were also studied. Correlational data of digit
      span performance and various intellectual, memory, and constructional measures
      was examined. Approximately 60% of all brain-damaged patients showed an
      impairment of digit span forward, while only 5% showed a similar impairment on
      the digit span backward task. These data indicate that digit span forward is a
      more sensitive measure of brain dysfunction from focal brain lesions. No
      difference was found in the performance of patients with right or left hemisphere
      lesions; however, the low incidence of aphasia (8%) in this sample may account in
      part for the relatively adequate performance by the left hemisphere patients.
      Although the current data regarding visual constructive deficits and impaired
      ability to repeat digits backward is inconclusive, there did not appear to be a
      strong relationship between these two functions for these patients. Digit
      repetition performance does appear to be related to both general intellectual
      ability and to performance on the Wechsler Memory Scale.

PMID- 16295106
TI  - Time as a variable in the performance of hemisphere-damaged patients on the
      Elithorn Perceptual Maze Test.
AB  - Eighteen LH aphasic patients, 11 LH nonaphasic patients, 19 RH patients and 30
      normal controls were compared on the Elithorn Perceptual Maze Test (EPMT) under
      both timed (T) and untimed (U) conditions. Results show that (a) normals were
      superior to LH groups within the T, but not the U, condition; (b) normal and LH
      groups were superior to RH groups under both T and U conditions; (c) the 2 LH
      groups did not differ from each other and (d) the RH group without language
      difficulty was superior to the RH group with language difficulty in the T, but
      not the U, condition. Additional findings were that (a) RH patients were able to
      process significantly fewer dots for maze solution than LH patients, (b) the more
      aphasic the patient, the more he improved his score from the T to the U
      condition. The data were discussed in terms of differential processing in R and
      LH groups, the RH groups being more likely to be impeded by the visual and
      spatial features of the task, the LH groups by the language and sequencing
      features.

PMID- 16295108
TI  - Normative data and screening power of a shortened version of the Token Test.
AB  - A 36-item-version of the Token Test is described and normative data obtained from
      its administration to 215 normal subjects are given. Years of schooling (but not
      age) were found to significantly affect the performance. The scores were
      corrected for this factor and the lower limit of the 90% tolerance interval
      around the mean of the adjusted scores was determined: it was found to correspond
      to 29 and left below it exactly 5% of the normal sample. The test was given to
      200 aphasic patients. Fourteen (7%) were found to have an adjusted score of 29 or
      more, namely would have been classified as non-aphasic. This is a percentage
      remarkably smaller than that (40%) obtained with a 10 sentence comprehension
      test, which supports previous studies pointing to the sensitivity of the Token
      Test to the presence of oral language disorders. On the basis of the aphasic
      patients' performance, cutting scores allowing evaluation of the severity of the
      comprehension deficit are provided. The 36-item-version of the test appears to be
      an useful and convenient device to diagnose aphasic impairment of language
      comprehension.

PMID- 16295107
TI  - Aphasic and amnesic patients' verbal vs. nonverbal retentive abilities.
AB  - Four different groups of patients (aphasics, alcoholic Korsakoffs, chronic
      alcoholics, and control patients) were asked to detect either repeated words
      presented orally, repeated words presented visually, repeated pictures or
      repeated shapes, during the presentation of a list of similarly constructed
      stimuli. It was discovered that on the verbal tasks, the number of words
      intervening between repetitions had more effect on the aphasics than on the other
      groups of patients. However, for the nonverbal picture repetition and shape
      repetition tasks, the aphasics' performance was normal, while the alcoholic
      Korsakoff patients were most affected by the number of intervening items. It was
      concluded that the aphasics' memory deficit demonstrated by the use of this
      paradigm was specific to the presentation of verbal material.

PMID- 16295109
TI  - Ictal prosopagnosia and epileptogenic damage of the dominant hemisphere. A case
      history.
AB  - This case report concerns a patient whose episodes of prosopagnosia appeared to
      be epileptic manifestations arising from the left occipital lobe. The underlying
      pathology, as revealed by radiologic and surgical findings, was an atrophic
      hypoplastic lesion of the left hemisphere, more prominent in the posterior
      sections, likely dating from early life. Removal of an arachnoidal cyst of the
      occipital pole and excision of the damaged gray matter were followed by the
      disappearance of the prosopagnosic seizures for the two years between the date of
      the surgical intervention and the publication of this article.

PMID- 16295110
TI  - Left hemisphere dominance for rhythmic elements in dichotically-presented
      melodies.
AB  - Right ear superiority was found for two groups of 24 subjects on a dichotic
      listening test of melodies each differing only in rhythm. In addition, no ear
      difference was found in the same two groups for a dichotic melodies test
      differing only in pitch or pitch pattern. Finally, the usual left ear superiority
      was seen for dichotic presentation of chords and the usual right ear superiority
      was seen for the dichotic presentation of digits. The results imply that in
      neither of the non-verbal (melodies) tests was the right hemisphere superior to
      the left. In fact for one test the reverse was true: the left hemisphere was
      superior to the right for melody recognition based on a rhythm cue. The apparent
      conflict between this and previous studies is explained by the notion that it is
      not the stimuli per se that govern hemispheric dominance, but rather the
      cognitive functioning required by the left and right hemispheres in order to
      process them.

PMID- 16295111
TI  - Directed attention and perceptual asymmetry to monaurally presented tones.
AB  - Forty-eight right-handed Ss were tested for simple reaction time (RT) to a
      monaurally presented 1000 Hz tone of 250 msec duration. Each S was tested in 3
      series comprising 7, 11 and 15 stimulus presentations (trials). In each series
      all stimuli but one (probe) were presented to a single ear. Ss were divided
      equally into right or left-ear attention groups on the basis of the ear receiving
      the non-probe trials. Right-ear attention resulted in equally good RTs to either
      attended or non-attended ear. Left-ear attention resulted in slower RTs than
      right-ear attention and showed a significant discrepancy between ears in favor of
      the non-attended ear. The results are interpreted as showing that neither simulus
      competition nor language processing are necessary conditions for eliciting
      auditory asymmetry. The data indicate that a cortically-mediated process of
      selective attention operates in the production of auditory asymmetries for some
      non-language sounds and that, as with language perception, it is the left
      cerebral hemisphere that is primarily involved.

PMID- 16295112
TI  - Cognitive mode and asymmetry in cerebral functioning.
AB  - Male graduate students from the fields of sculpture, psychology, and law were
      used to test the assumption that an individual's cognitive mode (verbal-analytic
      vs. spatial-holistic) is related to actual laterality in cerebral functioning. A
      measure of asymmetry of cognitive mode for each student, based on relative
      performance on three verbal-analytic tests compared to three spatial-holistic
      tests, successfully discriminated occupational groups. Laterality in cerebral
      functioning was indexed by relative reaction times to discriminate visual stimuli
      presented unilaterally to the left or right hemisphere. Reaction times to
      discriminate faces were less for the right hemisphere, while letters were
      discriminated faster by the left hemisphere. However, measures of cerebral
      laterality were not related to occupational group membership nor to asymmetry of
      cognitive mode. Asymmetry in performance on tests of cognitive mode may reflect
      an individual's general approach to problem solving, but is not closely related
      to laterality in cerebral functioning.

PMID- 16295113
TI  - Finger localization and the prediction of reading disability.
AB  - Tests of finger localization, letter naming, design copying, and receptive
      vocabulary were given to 100 kindergarten children. When the children had reached
      the end of first grade, their achievement in reading and arithmetic was related
      to these test performances. Poor readers had scores lower than good readers on
      all kindergarten measures, with their finger localization and letter naming
      performances being particularly poor. Finger localization scores correlated
      significantly with both reading and arithmetic achievement. These findings are
      interpreted as suggesting that the significance of finger localization as a
      predictor of reading and arithmetic achievement results from the ability of
      finger localization performance to reflect not simply one specific skill, but
      rather a number of important cognitive abilities.

PMID- 16295114
TI  - The influence of brain lateralization of function on a manual skill.
AB  - The present study considers the predictions of the brain lateralization of
      function hypothesis for the concurrent-task situation where the subject is
      required, to perform simultaneously a manual and a cognitive task. The manual
      task required the subject to successively press two keys with either the right or
      left hand, this being done concurrently with one of twelve different cognitive
      tasks. The cognitive tasks varied in terms of their verbal (left hemisphere) and
      non-verbal (right hemisphere) attributes. The results indicate that, for the
      concurrent verbal task conditions, only right-hand performance was disrupted
      while left-hand performance remained unchanged. For the non-verbal conditions
      both left and right hand performance was disrupted. These findings were
      interpreted in terms of brain lateralization of cognitive functions and possible
      hemispheric processes controlling manual performance.

PMID- 16295115
TI  - Sign comprehension in global aphasia.
AB  - Ten global aphasics and eight brain-damaged non-aphasics were given a test of
      sign comprehension. The test contained natural, animal and human signs. Subjects
      were matched for etiology, age and residual intellectual functioning. The global
      aphasics scored significantly lower than the nonaphasics on the test of sign
      comprehension, indicating that global aphasia might be reconsidered as a disorder
      of sign comprehension.

PMID- 16295116
TI  - Handedness and anxiety.
AB  - The anxiety scores of 23 left-handed, 12 mixed-handed and 35 right-handed college
      students were compared with the result that right-handers were significantly less
      anxious then both the left and the mixed-handed groups (which did not differ
      statistically). Since these data appear to be unique, generalizations from them
      was thought to be premature.

PMID- 16295117
TI  - Sex differences in functional brain asymmetry.
AB  - Adult male right-handers showed the expected pattern of verbal intellectual
      decline following left-hemisphere lesions, and depressed nonverbal intelligence
      following right-hemisphere lesions. In contrast, right-handed women did not show
      selective verbal or performance intellectual deficits after unilateral brain
      injury. These findings suggest a greater degree of functional brain asymmetry in
      right-handed men than women.

PMID- 16295118
TI  - Unilateral neglect of representational space.
AB  - Two patients showing left unilateral neglect were asked to describe imagined
      perspectives of familiar surroundings. Left-sided details were largely omitted in
      the descriptions. Some theoretical implications of the occurrence of unilateral
      neglect in representational space are briefly considered.

PMID- 16295119
TI  - On determining footedness.
AB  - The limitations of the most commonly used procedure for determining foot
      dominance are pointed out and alternatives are suggested.

PMID- 16295120
TI  - Computer assisted tomography in neuropsychological research: a simple procedure
      for lesion mapping.
AB  - A simple procedure for mapping the brain lesions observed on the CT scan sections
      onto a standard diagram of the cerebral hemisphere is described in detail, and
      its utility for neuropsychological research is briefly discussed.

PMID- 16295122
TI  - Congenital megacolon associated with enterocolitis and hypoproteinemia.

PMID- 16295121
TI  - EEG findings of posterior fossa tumors.

PMID- 16295123
TI  - Renal amyloidosis as a complication of Familial Mediterranean Fever in children.

PMID- 16295124
TI  - Therapy and prognosis of subdural collections.

PMID- 16295125
TI  - Diarrhea caused possibly by deficiency of sugar splitting enzymes.

PMID- 16295126
TI  - Rubinstein-Taybi syndrome.

PMID- 16295127
TI  - The benefits of smallness: developing a model for an effective rural child
      protection team.
AB  - To summarize these recommendations, the initiators of a rural child protection
      team must make full use of a small community's advantages. In this way, the
      benefits of smallness can be realized.

PMID- 16295128
TI  - Reaching children at risk: a model for training child welfare specialists.
AB  - An innovative model for the training of social welfare students in the special
      skills essential in child welfare work is predicated upon a classification system
      of children at risk and a continuum of services.

PMID- 16295129
TI  - Fathers anonymous: beyond the best interests of the sperm donor.
AB  - Current AID practices are based primarily on consideration of protecting the
      interests of practitioners and donors rather than recipients and children. The
      most likely reason for this is found in exaggerated fears of legal pitfalls. It
      is suggested that policy in this area should be dictated by maximizing the best
      interests of the resulting children. The evidence from the Curie-Cohen survey is
      that current practices are dangerous to children and must be modified.
      Specifically, consideration should be given to the following: 1. Removing AID
      from the practice of medicine and placing it in the hands of genetic counselors
      or other nonmedical personnel (alternatively, a routine genetic consultation
      could be added for each couple who request AID); 2. Development of uniform
      standards for donor selection, including national screening criteria; 3. A
      requirement that practitioners of AID keep permanent records on all donors that
      they can match with recipients; I would prefer this to become common practice in
      the profession, but legislation requiring filing with a governmental agency may
      be necessary; 4. As a corollary, mixing of sperm would be an unacceptable
      practice; and the number of pregnancies per donor would be limited; 5.
      Establishment of national standards regarding AID by professional organizations
      with input from the public; 6. Research on the psychological development of
      children who have been conceived by AID and their families. Dr. S.J. Behrman
      concludes his editorial on the Curie-Cohen survey by questioning the "uneven and
      evasive" attitude of the law in regard to AID, and recommending immediate
      legislative action: The time has come--in fact, is long overdue--when
      legislatures must set standards for artificial insemination by donors, declare
      the legitimacy of the children, and protect the liability of all directly
      involved with this procedure. A better public policy on this question is clearly
      needed. I have suggested that agreement with the need for "a better public
      policy" is not synonymous with immediate legislation. The problem with AID is
      that there are many unresolved problems with AID, and few of them are legal.
      There is no social or professional agreement on indications, selection of donors,
      screening of donors, mixing of donor sperm, or keeping records on sperm
      donations. Where there is agreement, such as in requiring the signature of the
      donor's wife on a "consent" form, the reasons for such agreement are unclear. It
      is time to stop thinking about uniform legislation and start thinking about the
      development of professional standards. Obsessive concern with self-protection
      must give way to concern for the child.

PMID- 16295130
TI  - Group therapy with sexually molested children.
AB  - It should be stressed that the young children's group was only a part of the
      overall treatment approach that forms the family context of the Child Sexual
      Abuse Treatment Program. Because the therapists also work with entire families,
      they have come to accept that the child is not the only victim. Often the mothers
      and fathers in this program were themselves victims of sexual assaults when they
      were children, and have carried this victim roles with them into adulthood. A
      child growing up in this family system will learn the victim role well. Her
      denial and/or fear of sexual aggression, as well as her role models for
      parenting, will perpetuate the cycle and make the sexual abuse of her own
      children a distinct possibility. The play therapy treatment seeks to break this
      cycle and restore the young child victim's self-respect by teaching new skills
      and providing different role models. The therapy seeks to help her tap her own
      power to become an adequate adult. Such therapeutic "undoing" or self
      reconstruction is a long process which probably takes as many paths as there are
      victims. Adults victimized as children frequently report periods of repression
      and denial, and it is likely that direct treatment of the child victim, when the
      incest comes to light, mitigates against development of such repression. The
      natural healing process must be respected. The child needs time to integrate the
      experience and its painful aftermath. Changing and healing do not take place all
      at once, or after one period of intervention. Therefore one important aspect of
      such therapeutic work is to give the child victims the tools to reach out for
      help and support in the future, when the pain of this early childhood experience
      may once again be an obstacle to growth.

PMID- 16295131
TI  - Agency change: a response to the needs of black families and children.
AB  - Many established voluntary child welfare agencies are now finding that the
      majority of their clients are black. Meeting their needs and those of the black
      community calls for deep-going changes in agency structure, orientation, and
      practice.

PMID- 16295132
TI  - A community-based comprehensive approach to serving adolescent parents.
AB  - A community-based social service center, working together with existing
      educational, medical, and social institutions, can offer a continuity of service
      to adolescent parents who cannot yet function independently and were not
      previously reached.

PMID- 16295133
TI  - The screening unit: an experimental approach to child protective service.
AB  - The Bronx screening unit was established on the assumption that in a populous
      urban area, a central registry reporting system would receive a sizable number of
      bogus or malicious reports. The unit tried to identify some of these reports by
      their characteristics and then to verify these suspicions through the diagnostic
      skill of experienced and highly motivated workers. The short-term goal was the
      easing of a workload crisis. The experiences of the screening unit showed that
      the process was highly successful, and represents an important way to use staff
      more efficiently in case management. During the 19-month period, an average of 93
      regular CPS workers processed 4282 cases, or 46 cases per worker. During that
      same period, four screening workers averaged 186 cases per worker. The screening
      process allows the regular CPS worker additional time to focus on serious cases.
      It also minimizes intrusion into the lives of persons harassed by bogus
      reporting. The process meets the legally mandated requirements of New York State
      and the federal government and provides for adequate case recording and record
      maintenance. One aspect of the Bronx screening unit worthy of special mention is
      the emphasis on referrals to community services. More than a third of the
      "unfounded" cases, though not requiring agency intervention, did warrant some
      type of social service and were referred for assistance. It is important that
      screening unit workers be familiar with community social service programs in
      order to serve as resource persons for clients. There exists a tendency to
      prematurely view cases for screening as easy or unfounded. Determining that a
      child abuse or neglect report is unfounded is the result of a specific
      investigative process, and only some cases lend themselves to shortening of this
      process. Administrative awareness of screening unit limitations will enable these
      units to function effectively and fulfill their primary responsibility of
      safeguarding children. Screening units can be a valuable adjunct to a child
      protective program, but they must not be viewed as a panacea for agency budget
      and staffing problems.

PMID- 16295134
TI  - [Reform discussion on the way to a new EU health care market - imitation or
      further development].

PMID- 16295135
TI  - [Nephrogenic fibrosing dermatopathy].

PMID- 16295136
TI  - The role of dendritic cells during infection.
AB  - The skin and the mucosa of the respiratory and gastrointestinal tracts are
      continuously exposed to microorganisms, but only a limited number of these enter
      the body and cause disease. To resist microbial infection, the host has developed
      a multitude of defense mechanisms involving the innate and adaptive immune
      systems. Dendritic cells (DCs) provide the link between these arms of the immune
      system. The initiation of an immune response is critically dependent on the
      activation of DCs, which can discriminate between different classes of
      microorganisms and elicit tailored antimicrobial immune responses. They have an
      extraordinary capacity to stimulate naive T cells and initiate primary immune
      responses. In turn, some pathogens interfere with DC function to block or delay
      their elimination by the host. Progress in understanding the role of DCs in the
      host response to microbes is reviewed.

PMID- 16295137
TI  - [Carcinogenesis: defect control systems and options for molecular therapy].
AB  - DNA mutations lead to multiple defects of different control systems necessary to
      regulate cell growth, cell death and cell invasion, thus resulting in the
      development of a malignant tumor. While the loss of single control systems can
      still be compensated by others, the destruction of the whole network on a
      molecular level will cause tumor growth. Knowledge about these control systems
      and their defects during carcinogenesis may it possible to design new therapeutic
      strategies. Among them, gene therapy offers promising treatment options.

PMID- 16295138
TI  - [Successful reduction of the SCORAD score by a short-time teaching method using a
      simplified skin model in children with atopic eczema in a 6-week comparison].
AB  - BACKGROUND: In order to achieve a long-term stabilizing effect on the clinical
      condition of the skin of patients with atopic eczema, it is imperative to perform
      consistent topical skincare. Because of time pressures during normal office
      visits, it is impossible to thoroughly counsel patients who suffer from atopic
      eczema. We performed a randomized and prospective comparative study to evaluate
      the outpatient effectiveness of a short-time but impressive teaching and
      counselling method using the skin model developed by Kardorff and Schnelle
      Parker. PATIENTS AND METHODS: Thirty outpatients between 3 and 6 years old with
      moderate or severe atopic eczema were evaluated. Half of the patients were
      trained by an active, 10-min demonstration with the skin model on day 0 and day
      14. Patients in the control group received verbal instructions of the same
      duration, as in routine dermatological practice. The SCORAD score was measured
      blindly on days 0, 14 and 42. RESULTS: After 42 days, the SCORAD score of the
      patients taught by the use of the Kardorff-Schnelle-Parker skin model was
      significantly reduced compared to the control group (P < 0.006). CONCLUSIONS: By
      counselling atopic children, even of preschool age, with the easily
      understandable skin model incorporating the sense of touch, better compliance
      concerning regular skincare can be achieved. We expect positive effects in the
      long-term management of atopic eczema.

PMID- 16295139
TI  - [Prognostic parameters and surgical strategies for facial melanomas].
AB  - BACKGROUND: In treated facial melanomas, the safety margins generally applied in
      other body sites cannot be achieved for functional and esthetical reasons. To
      date there are no controlled studies on safety margins for facial melanomas.
      Clinical parameters and surgical strategies influencing the prognosis of patients
      with a facial melanoma were evaluated in a retrospective study of melanoma
      patients in the Department of Dermatology of the University of Tuebingen (1980
      1999). PATIENTS AND METHODS: The 368 melanomas of the face comprised 9.3% of 3960
      primary stage I and II melanomas and 63% of the melanomas in the head and neck
      area. RESULTS: Multistep procedures, excisional biopsy for histological diagnosis
      followed by a subsequent resection of a clinical safety margin or re-excision
      when the tumor extended to the margin, were associated with a higher probability
      for recurrence-free survival (p = 0.0007), but had no statistical influence on
      overall survival. In a multivariate analysis, level of invasion (p = 0.0049),
      ulceration (p = 0.011), 3D-histology (p = 0.027) and defined safety margins
      (tumor thickness < or = 1.00 mm: 10 mm; > 1.00 mm 20 mm; lentigo maligna melanoma
      5 mm with 3D-histology) (p = 0,033) were independent significant risk factors for
      recurrence-free survival. Level of invasion (p = 0.032), ulceration (p = 0.029),
      3D-histology (p = 0.0047) were identified as independent significant risk factors
      for overall survival. Multivariate analysis did not show that the histological
      type of melanoma was of prognostic significance. CONCLUSION: Reduced safety
      margins can be employed in melanomas of the face. 3D-histology allows further
      reduction of safety margins, detects subclinical tumor strands and is correlated
      with an improved prognosis in patients with facial melanomas.

PMID- 16295140
TI  - [Nephrogenic fibrosing dermopathy].
AB  - Nephrogenic fibrosing dermopathy (NFD) is a scleromyxoedema-like disease favoring
      the extremities and trunk. Histologically there is a cellular fibrosis throughout
      the entire dermis. NFD is associated with renal insufficiency and dialysis,
      although the pathogenesis has not been elucidated. A 71-year-old woman developed
      classical symptoms of NFD on both legs within a few weeks after initiation of
      hemodialysis and concomitant antibiotic treatment followed by presumed drug
      eruption.

PMID- 16295142
TI  - [Cutaneous non-Langerhans' cell histiocytoses].

PMID- 16295141
TI  - [Scleroderma-like skin changes following administration of paclitaxel for the
      treatment of ovarian carcinoma].
AB  - A 61-year-old women with ovarian carcinoma was treated with surgery followed by 6
      cycles of paclitaxel (Taxol) and carboplatin, producing a complete remission.
      During the course of therapy, she developed diffuse cutaneous sclerosis and
      thickening along with edema, weight gain and malaise. While antinuclear
      antibodies were elevated, specific antibodies against Scl 70 were not found.
      Other routine laboratory investigations were normal or negative. 20 MHz
      sonography showed a thickened, echo-rich dermis, while the Cutometer documented
      decreased cutaneous elasticity. Esophageal manometry identified abnormal
      motility. Additional screening and imaging studies showed no further evidence of
      systemic involvement. A skin biopsy showed dermal sclerosis. Treatment with
      immunosuppressive agents - prednisolone, azathioprine, cyclophosphamide- and
      phototherapy, including both UVA-1 and PUVA combined with penicillin, produced no
      definite improvement. One year after the administration of paclitaxel, the
      sclerosis and malaise are only minimal improved. This case is the second
      documented association of scleroderma-like cutaneous changes with paclitaxel
      therapy. Similar cases have been more often described following treatment with
      the analog substance docetaxel (Taxotere).

PMID- 16295143
TI  - [Psychosomatic dermatology guideline. 15 January 2002 version].

PMID- 16295144
TI  - [From the working groups of the DDG. New impetus for dermatology 2. Meeting of
      the Dermato-Endocrinology Working Group].

PMID- 16295145
TI  - Physical disability and obesity.
AB  - Nearly 20% of US citizens are disabled. Epidemiologic studies have shown that
      people with physical disabilities have a 1.2- to 3.9-fold increase in obesity
      prevalence. Obesity is becoming a serious problem in disabled individuals. The
      mechanisms by which obesity occurs in people with physical disabilities is not
      clear, but pathophysiological changes of body composition and energy metabolism,
      physical inactivity, and muscle atrophy all favor the development of obesity.
      Health professionals should identify disabled patients at risk and provide early
      prevention guidance. Research is needed to help generate detailed clinical
      guidelines to promote weight control among people with physical disabilities.

PMID- 16295146
TI  - Vitamin A, mastitis, and mother-to-child transmission of HIV-1 through breast
      feeding: current information and gaps in knowledge.
AB  - Mastitis has been implicated as a risk factor for mother-to-child transmission
      (MTCT) of HIV-1 through breast-feeding. Maternal vitamin A deficiency is also
      associated with increased MTCT, as well as with episodes of mastitis in lactating
      animals. This review describes the complex interrelationship between vitamin A,
      mastitis, and MTCT of HIV-1 via mothers' milk. Current gaps in knowledge, as well
      as recommendations for future research efforts, are also discussed.

PMID- 16295147
TI  - Nutrition trends during 150 years of children's cookbooks.
AB  - This paper identifies trends in children's cookbooks for nutrition messages,
      cultural content, and food themes according to food guidance of the time. Except
      for those developed in government-sponsored nutrition programs since the 1970s,
      children's cookbooks seemingly have a preponderance of high-calorie dessert and
      party/fun recipes and limited vegetable recipes. In the past 150 years, the
      science of nutrition has grown from a focus on nitrogen to one on multiple
      nutrients and their interrelationships. Foods in the market have diversified in
      number and form, and a children's nutrition specialty has been introduced and
      expanded in many dimensions-including in the publishing of children's books.
      Because children's early food choices influence both their growth and health,
      factors impacting food choices need to receive more attention.

PMID- 16295148
TI  - Is maternal obesity a cause of poor lactation performance.
AB  - Several investigators have reported a relationship between maternal obesity and
      low rates of initiation and duration of breast-feeding. Recent research findings
      suggest that poor infant feeding behavior and reduced hormonal responses in the
      early postpartum period result in delayed lactogenesis and early cessation of
      breast-feeding among overweight/obese women.

PMID- 16295149
TI  - Is the small intestine a gluconeogenic organ.
AB  - Gluconeogenesis is responsible for the maintenance of blood glucose levels as
      hepatic glycogen stores become depleted. Traditionally, only liver and kidney
      have been believed to be capable of gluconeogenesis, but a gluconeogenic capacity
      for the small intestine has recently been proposed. This possibility is supported
      by the expression of key gluconeogenic enzymes and radiolabeled tracer
      experiments, but these data are not unequivocal and alternative roles can explain
      the presence of gluconeogenic enzymes in this organ.

PMID- 16295150
TI  - Loss.

PMID- 16295151
TI  - Nutrition education aimed at toddlers: an intervention study.
AB  - Weight problems in children are increasing at an alarming rate, especially among
      low-income populations. This concern requires effective strategies to promote
      healthy eating. A quasi-experiment was used to assess the effectiveness of an
      intervention, Nutrition Education Aimed at Toddlers (NEAT), aimed at enhancing
      parent-toddler feeding practices. The NEAT intervention comprises four nutrition
      lessons and structured reinforcements over 6 months. A convenience sample of 135
      low-income families participated in the study up to the first data collection
      wave. Complete data were available for 43 parent-toddler dyads in the
      intervention and 53 dyads in the control group. The results show that, compared
      to the controls, caregivers exposed to the intervention had significantly higher
      knowledge scores concerning toddler feedings. No statistically significant
      differences were found for measures of child and parent mealtime behaviors.
      Because it is generally easier to change knowledge than actual behaviors, our
      study results demonstrate the need to focus on other avenues to enhance parents'
      ability to feed toddlers appropriately.

PMID- 16295152
TI  - Parents' beliefs about children and gun safety.
AB  - This study sought to determine parents' beliefs about children and gun safety. A
      survey was sent to 230 parents of elementary age children addressing their
      beliefs about firearm storage, firearm safety training for children, and whether
      or not their child would handle a gun. Findings are based on the 82 returned
      surveys. Parents believed safe firearm storage was important to protect children.
      Only 22% of parents reported having a firearm in their home. However, of those
      reporting a firearm in the home, 85% did not practice safe gun storage despite
      reporting they believed it was important. These findings are supported by other
      studies that have found that parents have unrealistic perceptions about how their
      child will respond when a firearm is encountered. The only predictor of parents'
      incorrect perceptions about firearm safety training was the item "children will
      be safe if taught." This parental misperception provides further evidence that
      parents have unrealistic attitudes about children and guns.

PMID- 16295153
TI  - Narrowing the gap in childhood immunization disparities.
AB  - The reduction of health disparities among all people in the United States is a
      national health priority. Although immunization rates have improved in the past
      20 years, disparities continue to exist among ethnic and racial groups, across
      different socioeconomic classes, and in different geographic locations. Pediatric
      health care providers can play a key role in helping to narrow the gap in
      immunization coverage rates, thus reducing disparities. The purpose of this
      article is to (1) provide a review of the literature on disparities in
      immunization rates of children and adolescents, (2) provide suggestions for
      intervention to minimize immunization disparities, and (3) set an agenda for
      future research in this area.

PMID- 16295155
TI  - Safe sleep practices for hospitalized infants.
AB  - Guidelines were established over 10 years ago by professional and government
      agencies that have dramatically changed the practice of infant sleep positioning.
      Although these guidelines mainly focus care on the newborn and infant in their
      home by a parent, guardian or caregiver, hospital staff need to examine their
      compliance with these guidelines.The most controversial aspect of the "Back to
      Sleep" guidelines for the hospital setting is the parent and infant sharing a
      bed. Although parents may choose to sleep with their infant at home, the need for
      monitoring, ongoing assessment and care as well as the risk of entrapment or
      injury should be a priority in the delivery of optimal patient care in the
      hospital setting. The need for a policy was identified and developed by a
      multidisciplinary task force focusing on the physiological, behavioral and
      cultural aspects of cosleeping.

PMID- 16295154
TI  - Intervention pilot for parents of children with autistic spectrum disorder.
AB  - Parents of children who receive the diagnosis of autistic spectrum disorder (ASD)
      experience a situational crisis related to receiving the diagnosis, which causes
      feelings of distress and urgency to access services for the affected child. This
      paper describes a randomized trial (n = 31) that was conducted at a regional
      diagnostic center of a large metropolitan children's hospital to (a) refine a
      nursing intervention designed for parents of children with ASD and (b) to
      identify methodological revisions for a larger study. A secondary purpose was to
      test the effects of a post-diagnosis nursing intervention on parents' reports of
      stress, impact of event (diagnosis), and use of services after a child is newly
      diagnosed with ASD. The intervention consisted of usual care plus 3 hours contact
      with a pediatric nurse practitioner (PNP) for counseling, instruction, and
      assistance with implementation of the recommended treatment plan. The control
      group received only the usual care post-diagnosis, which consisted of a 1-hour
      consultation session to receive the results of diagnostic tests and a written
      copy of the recommended treatment plan provided by a developmental pediatrician
      and/or PNP. Between group differences in measures of "impact of event" and
      "perceived stress" were not statistically significant. This was attributed to a
      small sample size. A larger study is feasible and recommended with an expanded
      nursing intervention and a significantly larger sample recruited from an
      additional recruitment site. Nurses working with this special population must
      recognize that parents have information and counseling needs that begin after
      they receive the diagnosis of ASD for their child and can address these needs
      with a standardized nursing intervention.

PMID- 16295156
TI  - Self-concept and health locus of control: factors related to children's adherence
      to recommended asthma regimen.
AB  - PURPOSE: To determine the relationships of adherence to daily peak expiratory
      flow rate (PEFR) monitoring, recommended for asthma self-management, with self
      concept and health locus of control in a sample of 42 children, ages 7 through
      11. DESIGN/METHODS: Secondary analysis was conducted on data collected as part of
      our 5-week randomized, controlled asthma self-management clinical trial. During
      the study, the Piers-Harris Children's Self-Concept Scale (PHCSC) and Children's
      Health Locus of Control Scale (CHLOC) were administered at baseline (Week 1) and
      Week 5 for comparison, while adherence to electronically-measured peak flow
      monitor (PFM) was evaluated during Week 5. RESULTS: Adherence was positively
      correlated with higher self-concept (r(s) = .33, p = .03) and internal health
      locus of control (r(s) = .30, p = .05). Adherence to PFM and the intellectual and
      anxiety subscales of the PHCSC also were positively associated (r(s) = .38, p =
      .01, in both cases). CONCLUSIONS: Children who have a positive self-concept,
      particularly in the areas of intellect and anxiety, are more adherent to their
      recommended asthma regimen. Similarly, those who perceive their ability to
      control their health more positively adhere better to daily PEFR monitoring.
      These results suggest that children's adherence interventions may need to include
      components aimed at enhancing self-concept and health locus of control.

PMID- 16295157
TI  - Not just skin deep: a history of pediatric burn trauma.

PMID- 16295160
TI  - 18-year-old college woman with weight loss.

PMID- 16295159
TI  - Polycystic ovary syndrome (PCOS) in the adolescent patient: recommendations for
      practice.

PMID- 16295161
TI  - Two decades have passed ... and still it is her eyes that I remember: reflections
      of a pediatric nurse.
AB  - A pediatric nurse reflects on her practice by recounting her experience while
      caring for a child with Guillian Barre 20 years ago. Principles and lessons
      relevant to guide pediatric nursing practice in today's health care environment
      are identified.

PMID- 16295162
TI  - Follow-up of infants prenatally exposed to cocaine.
AB  - Maternal cocaine use during pregnancy continues to be of great concern for health
      care professionals. Research in this area has increased as investigators examine
      the effects of prenatal cocaine exposure in the infant/young child. This paper
      will critically review the literature, identify the primary care needs of infants
      and young children with a known history of prenatal cocaine exposure, and present
      guidelines for the primary care practitioner to monitor the infant's physiologic
      and developmental sequelae during the first 3 years of life. Findings in the
      literature demonstrate inconsistencies in regard to the physiologic and
      developmental outcomes of infants/young children prenatally exposed to cocaine.
      Further research is warranted, as it is evident from studies that not all
      investigators are controlling for confounding variables such as poly-drug use,
      which is necessary in isolating cocaine's effects. Subtle effects, however, have
      been reported from well-controlled studies and, thus, particular attention needs
      to be paid to early identification and interventions by primary care
      practitioners to prevent negative health outcomes. The guidelines proposed assist
      the practitioner with a thorough and focused approach to assessing the
      physiologic and developmental effects that are currently known to occur in the
      infant/young child prenatally exposed to cocaine.

PMID- 16295163
TI  - The 2005 London bombings and the Haddon matrix.

PMID- 16295164
TI  - Model describing the effect of employment of the United States military in a
      complex emergency.
AB  - The end of the Cold War vastly altered the worldwide political landscape. With
      the loss of a main competitor, the United States (US) military has had to adapt
      its strategic, operational, and tactical doctrines to an ever-increasing variety
      of non-traditional missions, including humanitarian operations. Complex
      emergencies (CEs) are defined in this paper from a political and military
      perspective, various factors that contribute to their development are described,
      and issues resulting from the employment of US military forces are discussed. A
      model was developed to illustrate the course of a humanitarian emergency and the
      potential impact of a military response. The US intervention in Haiti, Northern
      Iraq, Kosovo, Somalia, Bosnia, and Rwanda serve as examples. A CE develops when
      there is civil conflict, loss of national governmental authority, a mass
      population movement, and massive economic failure, each leading to a general
      decline in food security. The military can alleviate a CE in four ways: (1)
      provide security for relief efforts; (2) enforce negotiated settlements; (3)
      provide security for non-combatants; and/or (4) employ logistical capabilities.
      The model incorporates Norton and Miskel's taxonomy of identifying failing states
      and helps illustrate the factors that lead to a CE. The model can be used to
      determine if and when military intervention will have the greatest impact. The
      model demonstrates that early military intervention and mission assignment within
      the core competencies of the forces can reverse the course of a CE. Further study
      will be needed to verify the model.

PMID- 16295165
TI  - Recommended modifications and applications of the Hospital Emergency Incident
      Command System for hospital emergency management.
AB  - The Hospital Emergency Incident Command System (HEICS), now in its third edition,
      has emerged as a popular incident command system model for hospital emergency
      response in the United States and other countries. Since the inception of the
      HEICS in 1991, several events have transformed the requirements of hospital
      emergency management, including the 1995 Tokyo Subway sarin attack, the 2001 US
      anthrax letter attacks, and the 2003 Severe Acute Respiratory Syndrome (SARS)
      outbreaks in eastern Asia and Toronto, Canada. Several modifications of the HEICS
      are suggested to match the needs of hospital emergency management today,
      including: (1) an Incident Consultant in the Administrative Section of the HEICS
      to provide expert advice directly to the Incident Commander in chemical,
      biological, radiological, nuclear (CBRN) emergencies as needed, as well as
      consultation on mental health needs; (2) new unit leaders in the Operations
      Section to coordinate the management of contaminated or infectious patients in
      CBRN emergencies; (3) new unit leaders in the Operations Section to coordinate
      mental health support for patients, guests, healthcare workers, volunteers, and
      dependents in terrorism-related emergencies or events that produce significant
      mental health needs; (4) a new Decedent/Expectant Unit Leader in the Operations
      Section to coordinate the management of both types of patients together; and (5)
      a new Information Technology Unit Leader in the Logistics Section to coordinate
      the management of information technology and systems. New uses of the HEICS in
      hospital emergency management also are recommended, including: (1) the adoption
      of the HEICS as the conceptual framework for organizing all phases of hospital
      emergency management, including mitigation, preparedness, response, and recovery;
      and (2) the application of the HEICS not only to healthcare facilities, but also
      to healthcare systems. Finally, three levels of healthcare worker competencies in
      the HEICS are suggested: (1) basic understanding of the HEICS for all hospital
      healthcare workers; (2) advanced understanding and proficiency in the HEICS for
      hospital healthcare workers likely to assume leadership roles in hospital
      emergency response; and (3) special proficiency in constituting the HEICS ad hoc
      from existing healthcare workers in resource-deficient settings. The HEICS should
      be viewed as a work in progress that will mature as additional challenges arise
      and as hospitals gain further experience with its use.

PMID- 16295166
TI  - Symptom-based, algorithmic approach for handling the initial encounter with
      victims of a potential terrorist attack.
AB  - OBJECTIVES: This study intended to create symptom-based triage algorithms for the
      initial encounter with terror-attack victims. The goals of the triage algorithms
      include: (1) early recognition; (2) avoiding contamination; (3) early use of
      antidotes; (4) appropriate handling of unstable, contaminated victims; and (5)
      provisions of force protection. The algorithms also address industrial accidents
      and emerging infections, which have similar clinical presentations and risks for
      contamination as weapons of mass destruction (WMD). METHODS: The algorithms were
      developed using references from military and civilian sources. They were tested
      and adjusted using a series of theoretical patients from a CD-ROM chemical,
      biological, radiological/nuclear, and explosive victim simulator. Then, the
      algorithms were placed into a card format and sent to experts in relevant fields
      for academic review. RESULTS: Six inter-connected algorithms were created,
      described, and presented in figure form. The "attack" algorithm, for example,
      begins by differentiating between overt and covert attack victims (A covert
      attack is defined by epidemiological criteria adapted from the Centers for
      Disease Control and Prevention (CDC) recommendations). The attack algorithm then
      categorizes patients either as stable or unstable. Unstable patients flow to the
      "Dirty Resuscitation" algorithm, whereas, stable patients flow to the "Chemical
      Agent" and "Biological Agent" algorithms. The two remaining algorithms include
      the "Suicide Bomb/Blast/Explosion" and the "Radiation Dispersal Device"
      algorithms, which are inter-connected through the overt pathway in the "Attack"
      algorithm. CONCLUSION: A civilian, symptom-based, algorithmic approach to the
      initial encounter with victims of terrorist attacks, industrial accidents, or
      emerging infections was created. Future studies will address the usability of the
      algorithms with theoretical cases and utility in prospective, announced and
      unannounced, field drills. Additionally, future studies will assess the
      effectiveness of teaching modalities used to reinforce the algorithmic approach.

PMID- 16295168
TI  - Assessment of major and minor events that occurred in Italy during the last
      century using a Disaster Severity Scale score.
AB  - INTRODUCTION: Epidemiological research about disasters is difficult to perform.
      Most often, it must be completed retrospectively, since data collection may not
      be feasible or possible during the disaster. Now, there is a recognized need for
      a standard method to assess the severity of a disaster. OBJECTIVES: The aim of
      this paper is to assess the severity of the disasters that occurred in Italy
      during the 20th century, using a Disaster Severity Scale (DSS). Another goal is
      to find a standard method for the classification of previous disasters, test the
      feasibility and reliability of the use of the DSS, and improve disaster
      management and planning. METHODS: Data were obtained from formal reports of the
      Civil Defence Unit (Italy) and were used to calculate the DSS score. Disasters
      were classified into major and minor disasters, according to the numbers of
      deaths and severity of the damage. The number of deaths was compared with the
      obtained DSS score. A seasonal trend for different types of events was obtained
      to assess if there is a relationship between the type of event and the time of
      the year in which it occurred, as related to the weather conditions existing at
      that time. RESULTS: There were enough data to calculate a DSS score for 26 major
      events that caused death and economic damage, and occurred in Italy between 18
      March 1944 and 11 November 1999, and for 82 minor events, that occurred between
      October 1982 and December 1999. There were some significant peaks varying from
      different types of events during particular seasons, but the cause for those with
      the highest incidence is not clear. Events related to natural hazards were the
      only type of event that reached the highest DSS when considering the number of
      deaths, while no events associated with man-made hazards had a DSS score >8.
      CONCLUSION: The DSS score could be a reliable index for the assessment of events
      related to either natural or man-made disasters. Use of the DSS allows
      researchers to classify previous hazards by scoring each disaster's severity.
      Further studies in other countries could be useful to further validate the DSS.

PMID- 16295167
TI  - Disaster modeling: medication resources required for disaster team response.
AB  - INTRODUCTION: Responses to disasters involve many factors beyond personnel, such
      as medical and non-medical equipment and supplies. When disaster teams respond,
      they must do so with sufficient amounts of medicine and supplies to manage all of
      the patients expected for several days before re-supply. In order for this
      process to be efficient and expedient, accurate and advanced planning for
      supplies needed by disaster workers is necessary. These supplies must provide for
      general medical care and for hazard-specific problems. OBJECTIVE: To develop a
      model that provides the framework for determining supply requirements for the
      National Disaster Medical System, Disaster Medical Assistance Teams, or other
      responding disaster teams in a civilian environment. METHODS: A community
      hospital was modeled to determine patient characteristics when presenting to an
      emergency department (ED), including patient demographics and chief complaint,
      medications administered during the ED visit and prescribed at discharge, and
      laboratory tests ordered to assess disaster team supply requirements. Data were
      downloaded from a patient tracking software package and abstracted from various
      hospital data information systems. Data from the community hospital were compared
      with data published from two hurricane disasters by members of the National
      Disaster Medical System. RESULTS: To the extent possible, the model predicted the
      proportion of patient complaints and, therefore, the medicine and supplies needed
      for the management of these patients. CONCLUSION: This model offers a first step
      in preparing disaster medical teams for deployment.

PMID- 16295169
TI  - Thiopental vs. etomidate for rapid sequence intubation in aeromedicine.
AB  - INTRODUCTION: Although there is a general agreement that rapid sequence
      intubation (RSI) is the preferred technique for intubation in aeromedical care,
      several pharamacological regimens have been employed without clear evidence of
      which is superior. HYPOTHESIS: This study was designed to compare the use of
      etomidate (ETOM) with that of thiopental (THIO) as an adjunctive agent used with
      succinylcholine (SCh) for RSI in an urban, aeromedical system. METHODS: This was
      a retrospective, before-and-after study utilizing computer-assisted chart review.
      Adult patients who received THIO for RSI over a two-year period were compared to
      adult patients who received ETOM for RSI over a similar period, after a change in
      protocol, which mandated ETOM rather than THIO for all intubations. RESULTS: No
      difference was found in any of the primary endpoints. Stabilization time (13.1
      vs. 12.9 minutes), number of intubation attempts (1.1 vs. 1.2), successful first
      intubation attempts (90% vs. 82%), overall successful intubations (100% vs. 96%),
      and intubation time (18.4 vs. 21.7 seconds) were similar for all comparisons of
      THIO vs. ETOM (all p > 0.05). CONCLUSION: This study found no clinically relevant
      differences between the use of ETOM or THIO as adjuncts with SCh for RSI in the
      aeromedical setting.

PMID- 16295171
TI  - Benchmarking for hospital evacuation: a critical data collection tool.
AB  - In events such as earthquakes or terrorist attacks, hospitals may be victims of
      disasters. They may need to transfer patients to outside facilities rather than
      continue to provide on-site care. Following the Northridge earthquake, eight
      hospitals in the damaged area were the foci of a United States National Science
      Foundation study that examined the status of the hospitals' pre-event planning,
      post-event evacuation decision-making, and internal and external evacuation
      processes. Building on this experience, this paper offers a standardized data
      collection tool, which will enable researchers to record hospital evacuation
      information in a systematic manner so that comparable data can be accumulated,
      evacuation research methods can be improved, and consensus on methods can be
      reached. The study's principal subjects include: (1) hospital demographics; (2)
      description of existing disaster response plans; (3) an event's impacts on
      hospital operations; (4) decision-making and incident command; (5) movement of
      patients within the facility; (6) movement of patients to off-site institutions;
      and (7) hospital recovery.

PMID- 16295170
TI  - Strategies in evaluation and management of Bam earthquake victims.
AB  - BACKGROUND: On 26 December 2003, an earthquake measuring 6.5 on the Richter scale
      occurred in the city of Bam in southeastern Iran. Bam was destroyed completely, >
      43,000 people were killed, and 30,000 were injured. The national and
      international responses were quick and considerable. Many field hospitals were
      created and large numbers of patients were evacuated from their homes and
      transported to hospitals throughout Iran. Nearly 700 patients were transferred to
      Chamran hospital in Shiraz within the first 48 hours after the earthquake.
      METHODS: This is a retrospective study based on the medical records of earthquake
      casualties dispatched to Chamran Hospital. A screening tunnel composed of
      multiple stations was prepared before patients entered to facilitate the large
      influx of patients. Each of the victims was passed through this screening tunnel
      and assigned into one of three groups: (1) those needing emergency surgical
      intervention; (2) those needing less urgent surgery; and (3) those needing
      elective operations, supportive care, observation, and/or rehabilitation.
      RESULTS: Among the 708 patients, 392 were male (male/female ratio: 1.24) with a
      mean value of their ages of 30.5 years. (range: 1.5 months-70 years). Extremity
      fractures (136, 19%) were more common than were axial skeleton fractures (28,
      4%). Out of the total 708 patients, 152 (21.5%) patients needed emergency
      operations, 26 (4%) needed less urgent surgery, and 530 (74.5%) required wound
      care or antibiotic therapy and other forms of supportive care. Some complications
      occurred, such as two patients with compartment syndromes of the leg, three
      required below-the-knee amputation, eight suffered acute renal failure, two
      developed fat emboli syndrome, and one had a brain injury that resulted in death.
      CONCLUSION: A comprehensive disaster plan is required to ensure a prompt disaster
      response and coordinated management of a multi-casualty incident. This can
      influence the outcomes of patients directly. A patient screening tunnel has
      advantages in rapid and effective evaluation and management of victims in any
      multi-casualty incident.

PMID- 16295172
TI  - Blackout 2003: preparedness and lessons learned from the perspectives of four
      hospitals.
AB  - INTRODUCTION: The blackout in North America of August 2003 was one of the worst
      on record. It affected eight US states and parts of Canada for >24 hours.
      Additionally, two large US cities, Detroit, Michigan and Cleveland, Ohio,
      suffered from a loss of water pressure and a subsequent ban on the use of public
      supplies of potable water that lasted four days. A literature review revealed a
      paucity of literature that describes blackouts and how they may affect the
      medical community. METHODS: This paper includes a review of after-action reports
      from four inner-city, urban hospitals supplemented accounts from the authors'
      hospital's emergency operations center (EOC). RESULTS: Some of the problems
      encountered, included: (1)lighting; (2) elevator operations; (3) supplies of
      water; (4) communication operations; (5) computer failure; (6) lack of adequate
      supplies of food; (7) mobility to obtain X-ray studies; (8) heating, air
      condition, and ventilation; (9) staffing; (10) pharmacy; (11) registration of
      patients; (12) hospital EOC; (13) loss of isolation facilities; (14) inadequate
      supplies of paper; (15) impaired ability to provide care for non-emergency
      patients; (16) sanitation; and (17) inadequate emergency power. DISCUSSION: The
      blackout of 2003 uncovered problems within the US hospital system, ranging from
      staffing to generator coverage. This report is a review of the effects that the
      blackout and water ban of 2003 had on hospitals in a large inner-city area. Also
      discussed are solutions utilized at the time and recommendations for the future.
      CONCLUSION: The blackout of 2003 was an excellent test of disaster/emergency
      planning, and produced many valuable lessons to be used in future events.

PMID- 16295174
TI  - Door poems.

PMID- 16295173
TI  - Overview of the blood donation in acute post-tsunami in Thailand.

PMID- 16295175
TI  - Reflections on a presidency.
AB  - The term of each SOHN president is two years. One of the president's many duties
      and privileges is to preside over the opening ceremony at the Annual Congress and
      Nursing Symposium each fall, marking the official opening of the five-day
      conference, which includes educational, collegial, and social activities.
      Following is the outgoing President Helene Krouse's address, delivered on
      September 24, 2005 at the 29th Annual Congress in Los Angeles, California, which
      reviews and salutes SOHN's past presidents.

PMID- 16295176
TI  - Reasons to customize a tracheostomy patient education booklet.
AB  - Given the breadth of commercial materials currently available for patient
      education, healthcare providers are often led to believe that it is no longer
      necessary to generate institution-specific patient education materials. This
      paper describes the comprehensive methods and criteria used by a group of
      inpatient nurse educators to critically review their existing booklet for
      tracheostomy patient education against those available commercially. The group
      concluded that a revised institution-specific publication remains the best
      complement to their program for tracheostomy patient teaching.

PMID- 16295177
TI  - What in the world is the NIWI?

PMID- 16295178
TI  - Reasoning and requirements.

PMID- 16295179
TI  - Hereditary hemochromatosis.

PMID- 16295180
TI  - A brave, new laboratory world.

PMID- 16295181
TI  - Coalition strives for phlebotomy personnel standards.

PMID- 16295182
TI  - Greg Porter brings an open mind to Tecan.

PMID- 16295183
TI  - Clinical Lab-Tech Day serves as education model.

PMID- 16295184
TI  - Underage allied-health students require special guidelines.

PMID- 16295185
TI  - Radiologic case study. Seronegative spondyloarthropathy associated with Crohn's
      disease.
AB  - Seronegative arthropathies are a heterogeneous group of arthropathic disorders
      with negative rheumatoid factors and varying association with the HLA-B27
      phenotype. The distribution of involvement and pattern of presentation within
      this group is variable. However, these disorders share common features of
      aggressive erosions, bone density preservation, and proliferative bony response
      to inflammation. These features along with asymmetric involvement of the
      appendicular skeleton, sacroiliitis, and spine abnormalities usually allow
      differentiation from rheumatoid arthritis and other inflammatory arthritides
      based on imaging studies.

PMID- 16295186
TI  - The lesson of Sam the shirt-maker.

PMID- 16295187
TI  - Arthroscopic biceps tenodesis using the percutaneous, intra-articular trans
      tendon technique: preliminary results.
AB  - The percutaneous intra-articular trans-tendon procedure relieved pain, increased
      or maintained strength and function, and did not cause a cosmetic deformity in
      this small consecutive series of patients.

PMID- 16295188
TI  - Percutaneous plate fixation of comminuted ulnar fractures.
AB  - The superficial location of ulnar fractures allows minimally invasive insertion
      of percutaneous plates, which improves stability and creates a friendly healing
      environment.

PMID- 16295189
TI  - Why is the microbiology lab calling about an extended-spectrum beta-lactamase
      bacterium from a wound culture?
AB  - As more and more gram-negative bacteria produce extended-spectrum beta
      lactamases, it is important that physicians know what to do when these bacteria
      cause postoperative infections in patients.

PMID- 16295190
TI  - Avoiding the potential pitfalls of minimally invasive total knee surgery.
AB  - The performance of TKA through less than traditional visualization presents a new
      set of problem areas.

PMID- 16295191
TI  - Spondylolysis and spondylolisthesis in the athlete.
AB  - Though athletes may be able to return to their sport after treatment of
      spondylolysis and spondylolisthesis, prevention of back injury in at-risk patient
      athletes should be the treating physician's primary goal.

PMID- 16295192
TI  - Reducing the risk of deep wound infection in primary joint arthroplasty with
      antibiotic bone cement.
AB  - Despite significant advances in intraoperative antimicrobial procedures, deep
      wound infection remains the most serious complication associated with primary,
      cemented total joint arthroplasty. A systematic review was conducted to evaluate
      studies of antibiotic bone cement prophylaxis for reducing the risk of deep wound
      infection. The literature included 22 articles providing estimates of the
      prophylactic effectiveness of antibiotic cement. In reducing deep wound
      infection, antibiotic cement was consistently superior to plain cement, similar
      to systematic antiobiotics, and independent and additive in effect when combined
      with other prophylactic measures. Randomized controlled trials in particular had
      important methodological limitations. However, the collective results nearly
      unanimously favored prophylactic use of antibiotic cement in primary arthoplasty
      procedures.

PMID- 16295193
TI  - Osteoporosis: a global assessment of clinical and imaging features.

PMID- 16295194
TI  - Computer-assisted two-dimensional preoperative planning for total hip
      arthroplasty: clinical evaluation.
AB  - The purpose of this study is to clinically validate a new two-dimensional
      preoperative planning software for cementless total hip arthroplasty (THA).
      Manual and two-dimensional computer-assisted planning were compared by an
      independent observer for each of the 30 patients with osteoarthritis who
      underwent THA. This study showed that there were no statistical differences
      between the results of both preoperative plans in terms of stem size and neck
      length (<1 size) and hip rotation center position (<5 mm). Two-dimensional
      computer-assisted preoperative planning provided successful results comparable to
      those using the manual procedure, thereby allowing the surgeon to simulate
      various stem designs easily.

PMID- 16295195
TI  - Variation of carrying angle with age, sex, and special reference to side.
AB  - We measured the carrying angle using a universal full-circle manual goniometer on
      the dominant and non-dominant extremity of the elbow in 1275 healthy volunteers
      (631 males, 644 females) with a mean age of 22.87+/-15.99 years (range: 2-91
      years). In the right arm dominant group, right carrying angle was 11.25 degrees
      +/- 3.73 degrees and left carrying angle was 10.57 degrees +/- 3.63 degrees
      (P<.001). In left arm dominant group, right carrying angle was 10.65 degrees +/-
      3.99 degrees and left carrying angle was 12.93 degrees +/- 4.22 degrees (P<.001).
      The carrying angle of dominant arm was found to be significantly higher than the
      non-dominant arm in both sexes. The carrying angle of dominant and non-dominant
      arms were found to be significantly higher in patients aged >14 years than that
      of patients aged < or = 14 years; females ranked higher than males.

PMID- 16295196
TI  - The effect of an extended flexor carpi radialis approach on blood flow to the
      distal radius: a cadaveric study.
AB  - The effect of an extended flexor carpi radialis approach on the blood supply of
      the radius was examined in six (3 paired) fresh frozen cadaver limbs after
      injection with India ink and clearing using a modified Spalteholz technique. An
      extended flexor carpi radialis approach to the distal radius was made in the left
      limb in each of the three-paired limbs. The right limb served as a nonoperative
      control. Following perfusion of the arterial vasculature of each limb with India
      ink, serial transverse sections were cut and the intraosseous blood supply
      evaluated using a modified Spalteholz technique. Both controls and surgical
      specimens demonstrated complete cortical penetration from endosteal vessels in
      the proximal and midsections of the radius. In the distal radius, surgical
      specimens demonstrated reduced perfusion volarly, however there continued to be
      perfusion of ink through intact dorsal and ulnar metaphyseal perforating
      arteries. Persistent vascular perfusion to the distal radius remains through
      intact endosteal vessels and metaphyseal perforators of extensive surgical soft
      tissue stripping.

PMID- 16295197
TI  - Posterior shoulder fracture dislocation in an osteogenesis imperfecta patient.

PMID- 16295198
TI  - Routine transurethral resection of the prostate complicated by severe acute hip
      pain.

PMID- 16295199
TI  - A minimal subtalar approach to fix a calcaneal fracture and a lateral process of
      talus fracture in a diabetic obese patient.

PMID- 16295200
TI  - Can habitual sleep duration harbor sleep debt?

PMID- 16295201
TI  - Continuous positive airway pressure therapy for obstructive sleep apnea syndrome:
      do the dollars make sense?

PMID- 16295202
TI  - Timed melatonin treatment for delayed sleep phase syndrome: the importance of
      knowing circadian phase.

PMID- 16295203
TI  - A link between short sleep and obesity: building the evidence for causation.

PMID- 16295204
TI  - Fostering the independence of new investigators.

PMID- 16295205
TI  - COLLAPSE: economic impact of aging and sleep on modern societies.

PMID- 16295206
TI  - Sleep and memory: the ongoing debate.
AB  - The last 10 years have produced a wealth of scientific studies reporting a role
      for sleep in offline memory processing. Despite this evidence, debate continues
      to rage over the very existence of sleep-dependent learning and memory
      processing. We briefly review here the evidence in support of sleep's role in
      memory consolidation.

PMID- 16295207
TI  - Time for the sleep community to take a critical look at the purported role of
      sleep in memory processing.
AB  - We have previously presented a wealth of data refuting the proposal that memories
      are processed or consolidated in sleep. Our objections have been largely ignored,
      creating the impression that the hypothesized role for sleep in memory processing
      is an established fact rather than a highly controversial and unresolved issue.
      We briefly review the main arguments against a role for sleep in learning/memory.

PMID- 16295208
TI  - Rat strain differences in freezing and sleep alterations associated with
      contextual fear.
AB  - STUDY OBJECTIVE: To examine rat strain differences in fear responses and
      subsequent alterations in sleep associated with contextual fear. DESIGN:
      Recordings for each strain were obtained of nondisturbed baseline sleep and of
      sleep after exposure to a novel chamber (handling control). Afterward, the rats
      were subjected to shock training for 2 sessions (ST1, ST2) and to contextual fear
      (CF) alone. Percentage time spent in freezing (FT%) was observed during ST1, ST2
      and CF exposures. Sleep was recorded for 20 hours (8-hour light and 12-hour dark
      period) following ST1, ST2 and CF. SETTING: NA SUBJECTS: The subjects were 2
      inbred rat strains (Fischer 344 [F344] and Lewis [LEW] and one outbred rat strain
      (Wistar [WST]). INTERVENTIONS: The rats were surgically implanted with electrodes
      for recording electroencephalogram and electromyogram for determining arousal
      state. MEASUREMENTS AND RESULTS: Strain rankings for FT% were F344 = LEW > WST
      during ST2 and CF. LEW and WST rats exhibited decreased rapid eye movement sleep
      (REM) after shock training and CF compared with baseline and control; F344 rats
      did not. F344 and WST rats showed increased dark-period REM after ST1, ST2, and
      CF compared with baseline but not with control. CONCLUSIONS: Shock training and
      CF induce immediate reductions in REM in rats. However, strain differences in the
      amount of REM decrease did not simply relate to the strength of fear responses
      during shock training and CF. We speculate that reported strain differences in
      stress hormones, particularly prolactin, may contribute to strain differences in
      fear-induced alterations in REM.

PMID- 16295209
TI  - Sleep in spousal caregivers of people with Alzheimer's disease.
AB  - STUDY OBJECTIVE: This study examined differences in objective and subjective
      measures of sleep between caregivers and noncaregivers. DESIGN: Cross-sectional
      design. SETTING: All assessments were conducted within the home. PARTICIPANTS:
      Seventy-three community-dwelling spousal caregivers of patients with Alzheimer's
      disease and 40 noncaregiving controls. MEASUREMENTS AND RESULTS: Subjects
      completed a semistructured interview on sociodemographics, cognitive status of
      the care recipient, self-reported sleep quality, and functional outcome. A
      polysomnogram was conducted. Caregivers of patients with moderate to severe
      Alzheimer's disease reported significantly more sleep problems (P<.05) and more
      functional impairment as a result of sleepiness than noncaregivers (P<.01).
      Objectively, older caregivers of those with moderate to severe Alzheimer's
      disease slept less than older noncaregivers (P<.05); there were no other
      significant differences in objective sleep measures. There was a main effect for
      age, with older caregivers and older noncaregivers having lower sleep efficiency,
      less slow-wave sleep, and more stage 1 sleep than younger caregivers and
      noncaregivers (P<.05). CONCLUSIONS: This study suggests that nighttime sleep is
      shorter but not otherwise disrupted in caregivers of patients with moderate to
      severe Alzheimer's disease compared with noncaregivers, and the impact of
      caregiving on sleep disturbance may be most salient for older caregivers. It is
      possible that these older caregivers are more vulnerable to the effects of sleep
      disruption and thus have trouble falling back to sleep when the time is afforded
      them. Future work is needed to examine the differences in care practices in
      caregivers by age and dementia severity. Perhaps more importantly, studies
      examining the health consequences of shortened sleep in this group are needed.

PMID- 16295211
TI  - Sleep duration, subjective sleep need, and sleep habits of 40- to 45-year-olds in
      the Hordaland Health Study.
AB  - STUDY OBJECTIVE: To report the distribution of various sleep parameters in a
      population-based study. DESIGN: Population-based cross-sectional study with self
      administered questionnaires. SETTING: Conducted as part of the Hordaland Health
      Study '97-'99 in collaboration with the Norwegian National Health Screening
      Service. PARTICIPANTS: 8860 subjects, aged 40 to 45 years, answered the sleep
      questionnaire part of the study. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS:
      Reports on habitual bedtimes, rise times, subjective sleep need, and various
      sleep characteristics were used in this study. Mean (+/- SD) nocturnal sleep
      duration during weekdays in men was 6 hours 52 minutes (+/- 55 minutes); in women
      7 hours 11 minutes (+/- 57 minutes). Mean subjective sleep need was 7 hours 16
      minutes (+/- 52 minutes) in men; 7 hours 45 minutes (+/- 52 minutes) in women.
      Sleep duration was shorter in shift workers and longer in married subjects and in
      those living in rural areas. Subjective sleep need was higher in subjects
      reporting poor subjective health and in subjects living in rural areas. In total,
      these variables accounted for only around 3% of the variance in sleep duration
      and sleep need. Ten percent of the men and 12.2% of the women reported frequent
      insomnia. CONCLUSIONS: The wide distribution of sleep duration and subjective
      sleep need indicate large interindividual variations in these parameters. There
      were pronounced sex differences in these variables and in most of the sleep
      characteristics studied. Shift work, urban-rural living, marital status, and
      education in men were sources of significant, but small, variations in sleep
      duration.

PMID- 16295210
TI  - Interindividual variation in sleep duration and its association with sleep debt
      in young adults.
AB  - STUDY OBJECTIVE: To determine whether variation in sleep duration reflects
      variation in sleep need or self-imposed sleep restriction. DESIGN: After habitual
      bedrest duration of participants was assessed during a 2-week outpatient
      protocol, volunteers were scheduled to sleep according to this schedule for 1
      week prior to and the first night after admission to a general clinical research
      center. The inpatient protocol included multiple sleep latency testing on the
      second day and sleep recordings during a bedrest extension protocol that included
      16 hours of sleep opportunity (12 hours at night and 4 hours at midday) for 3
      consecutive days. SETTING: Outpatient monitoring followed by inpatient assessment
      of sleep. PARTICIPANTS: Seventeen healthy volunteers (10 women) aged 18-32 years
      without clinical sleep disorders. INTERVENTIONS: Extension of sleep opportunity.
      MEASUREMENTS AND RESULTS: The habitual bedrest duration varied from 6.1 to 10.3
      hours. Individuals with shorter habitual bedrest duration fell asleep more
      quickly and frequently during the multiple sleep latency test than did those with
      longer habitual bedrest duration. On the first day of extended sleep opportunity,
      the total sleep time of all individuals was greater than their habitual bedrest
      duration; the average increase in total sleep time was 4.9 hours (P = 0.001). The
      increase in total sleep time declined across the 3 day bedrest-extension protocol
      (P = 0.003 for trend). During the third day of increased sleep opportunity, the
      total sleep time was negatively associated with habitual bedrest duration (P =
      0.005); individuals with shorter habitual bedrest duration continued to sleep
      more than those with longer habitual bedrest duration. CONCLUSION: Those
      individuals with shorter habitual sleep durations carry a higher sleep debt than
      do those with longer habitual sleep duration. Interindividual variation in sleep
      duration may primarily reflect variation in self-selected sleep restriction or
      wake extension.

PMID- 16295212
TI  - Phase-dependent treatment of delayed sleep phase syndrome with melatonin.
AB  - STUDY OBJECTIVE: Delayed sleep phase syndrome (DSPS) is a circadian-rhythm sleep
      disorder characterized by abnormally late sleep and wake times. Melatonin, taken
      in the evening, advances sleep and circadian phase in patients with DSPS.
      However, little is known about the most effective dose or time of administration.
      In the present study, we tested the effectiveness of melatonin to advance the
      timing of sleep and circadian phase in individuals with DSPS. DESIGN: Following
      baseline assessment of sleep and circadian phase, subjects were randomly assigned
      to 1 of 3 treatment groups. The administration of melatonin (0.3 or 3.0 mg) or
      placebo was double-blinded. SETTING: All procedures were conducted on an
      outpatient basis. PARTICIPANTS: Thirteen subjects with DSPS, recruited via
      flyers, advertisements, and referrals from the Sleep Clinic, completed this
      study. INTERVENTIONS: Melatonin (0.3 or 3.0 mg) or placebo was administered
      between 1.5 and 6.5 hours prior to dim light melatonin onset for a 4-week period.
      MEASUREMENTS AND RESULTS: Both doses of melatonin advanced the circadian phase of
      endogenous melatonin. The magnitude of phase advance in dim-light melatonin onset
      correlated strongly with the time of melatonin administration, with earlier times
      being more effective (r2 = 0.94, P < .0001). Similar, though weaker,
      relationships were obtained between the timing of melatonin administration and
      changes in sleep time. CONCLUSIONS: These results indicate that melatonin
      advances the circadian clock and sleep in patients with DSPS in a phase-dependent
      manner. This is the first study that reports a relationship between timing of
      melatonin administration and phase changes in patients with DSPS.

PMID- 16295213
TI  - Age modulates the effects of sleep restriction in women.
AB  - STUDY OBJECTIVES: To investigate how age influences the effects of 3 nights of
      sleep restriction in healthy women. DESIGN: After a baseline night, sleep was
      restricted to 4 hours during 3 consecutive nights. One recovery night followed
      the sleep restriction. SETTING: The sleep-restriction experiments were conducted
      under standardized conditions with continuous electroencephalographic ambulatory
      recordings. Before entering the study, the subjects underwent a polysomnographic
      recording for exclusion of sleep disorder and adaptation to the laboratory
      environment. PARTICIPANTS: Eleven young women (aged 20-30 years) and 10 older
      women (aged 55-65 years) were included in the study. INTERVENTION: The subjects
      were admitted to the sleep laboratory for 5 consecutive nights and days. After 1
      baseline night, 3 nights of sleep restriction to 4 hours were performed and were
      followed by 1 recovery night of 8 hours. Continuous ambulatory
      electroencephalographic recordings were performed, as well as the Maintenance of
      Wakefulness Test (8:30 AM and 1:30 PM), the Stanford Sleepiness Scale, and the
      Psychomotor Vigilance Test. RESULTS: Young women were more affected by sleep
      restriction than were the older women. This was evidenced by more sleep onsets
      during the Maintenance of Wakefulness Test sessions in the young subjects, who
      also rated themselves more sleepy than the older women. CONCLUSIONS: Age
      influences the impact of sleep restriction on vigilance in women.

PMID- 16295214
TI  - Inadequate sleep as a risk factor for obesity: analyses of the NHANES I.
AB  - STUDY OBJECTIVES: Sleep deprivation has been hypothesized to contribute toward
      obesity by decreasing leptin, increasing ghrelin, and compromising insulin
      sensitivity. This study examines cross-sectional and longitudinal data from a
      large United States sample to determine whether sleep duration is associated with
      obesity and weight gain. DESIGN: Longitudinal analyses of the 1982-1984, 1987,
      and 1992 NHANES I Followup Studies and cross-sectional analysis of the 1982-1984
      study. SETTING: Probability sample of the civilian noninstitutionalized
      population of the United States. PARTICIPANTS: Sample sizes of 9,588 for the
      cross-sectional analyses, 8,073 for the 1987, and 6,981 for the 1992 longitudinal
      analyses. MEASUREMENTS AND RESULTS: Measured weight in 1982-1984 and self
      reported weights in 1987 and 1992. Subjects between the ages of 32 and 49 years
      with self-reported sleep durations at baseline less than 7 hours had higher
      average body mass indexes and were more likely to be obese than subjects with
      sleep durations of 7 hours. Sleep durations over 7 hours were not consistently
      associated with either an increased or decreased likelihood of obesity in the
      cross-sectional and longitudinal results. Each additional hour of sleep at
      baseline was negatively associated with change in body mass index over the follow
      up period, but this association was small and statistically insignificant.
      CONCLUSIONS: These findings support the hypothesis that sleep duration is
      associated with obesity in a large longitudinally monitored United States sample.
      These observations support earlier experimental sleep studies and provide a basis
      for future studies on weight control interventions that increase the quantity and
      quality of sleep.

PMID- 16295215
TI  - Changes in symptoms of sleep-disordered breathing during pregnancy.
AB  - BACKGROUND: Although incident snoring is common in pregnant women and has been
      proposed as a potential risk factor for adverse maternal-fetal outcomes, the
      development of sleep-disordered breathing during pregnancy has not been
      prospectively described. METHODS: Using the Apnea Symptom Score from the
      Multivariable Apnea Prediction Index and the Epworth Sleepiness Scale, we
      prospectively assessed symptoms of sleep-disordered breathing and daytime
      somnolence in 155 women to determine whether symptoms increased during pregnancy
      and the characteristics associated with increasing symptoms. RESULTS: We found
      that sleep-disordered breathing symptoms (Apnea Symptom Score, 0.44 (SEM 0.58) vs
      0.95 (0.09, P < .001) and the degree of daytime somnolence (Epworth Sleepiness
      Scale, 8.6 (0.3) vs 10.2 (0.4), P = .0003) increased significantly during
      pregnancy. Women with higher baseline body mass indexes and greater increases in
      neck circumference during pregnancy reported higher apnea symptom scores. Of the
      155 subjects, 11.4% reported an increase in Apnea Symptom Score of 2 units or
      more, consistent with a clinically significant increase in symptoms; these women
      experienced a significantly greater increase in subjective sleepiness than other
      subjects (P = .03). Excessive daytime somnolence (Epworth Sleepiness Scale > 10)
      was prevalent throughout pregnancy (31.0%-45.5%). CONCLUSIONS: Our data
      demonstrate that symptoms of sleep-disordered breathing increase during pregnancy
      and that more than 10% of our subjects may be at risk for developing sleep apnea
      during pregnancy. Excessive daytime somnolence was highly prevalent even early in
      pregnancy and became increasingly common as pregnancy progressed.

PMID- 16295216
TI  - Utilization of healthcare resources in obstructive sleep apnea syndrome: a 5-year
      follow-up study in men using CPAP.
AB  - STUDY OBJECTIVES: Patients with untreated obstructive sleep apnea syndrome (OSAS)
      have higher healthcare utilization than matched controls. However, the long-term
      impact of continuous positive airway pressure (CPAP) use on healthcare
      utilization is unknown. DESIGN: Retrospective observational cohort study.
      SUBJECTS: There were 342 eligible men with OSAS and matched controls on whom
      there were utilization data for 5 years prior to initial OSAS diagnosis and for
      the 5 years on CPAP treatment of the cases. INTERVENTIONS: Patients were treated
      with CPAP. RESULTS: Patients with OSAS were typical cases (mean +/- SD): age,
      48.2 +/- 0.6 years; body mass index, 35.6 +/- 0.4 kg/m2; Epworth Sleepiness Scale
      score, 14.2 +/- 0.3; apnea-hypopnea index, 47.1 +/- 1.8 events per hour. The
      number of physician visits were higher by 3.46 +/- 0.2 (95% confidence interval
      [CI]: 2.57 to 4.36) in cases in the year before diagnosis, compared with the
      fifth year before diagnosis, then decreased over the next 5 years by 1.03 +/-
      0.49 (95% CI: -1.99 to -0.07)(P<.0001). Physician fees, in Canadian dollars, were
      higher by dollars 148.65 +/- dollars 27.27 (95% CI: 95.12 to 202.10) in cases in
      the year before diagnosis, compared with the fifth year before diagnosis, and
      then decreased over the next 5 years by dollars 13.92 +/- dollars 27.94(95%CI: 
      68.68 to 40.83)(P=.0009). Preexisting ischemic heart disease at the time of OSAS
      diagnosis predicted about a 5-fold increase in healthcare utilization between the
      second and fifth year of treatment. CONCLUSIONS: Treatment of OSAS reversed the
      trend of increasing healthcare utilization seen prior to diagnosis. Preexisting
      ischemic heart disease results in a negative impact on healthcare utilization.
      CPAP results in a long-term health benefit, as measured by the use of healthcare
      services.

PMID- 16295217
TI  - Vibration enhances interleukin-8 release in a cell model of snoring-induced
      airway inflammation.
AB  - STUDY OBJECTIVES: To test a cell model of snoring-induced airway inflammation and
      to assess whether a vibration stimulus simulating the one experienced by airway
      tissues in snoring patients induces inflammation in airway epithelial cells.
      DESIGN: Prospective controlled study in cell culture. SETTING: University
      laboratory. PATIENTS OR PARTICIPANTS: Human bronchial epithelial cells (BEAS-2B
      cell line). INTERVENTIONS: Cell cultures were subjected to vibration (60 Hz, +/-
      0.3 mm) for time periods of 6 hours, 12 hours, and 24 hours. The vibratory
      stimulus was applied with and without treatment with inhibitors of the 3 main
      pathways of mitogen-activated protein kinases (MAPK): p38, MEK1/2, and JNK.
      MEASUREMENTS AND RESULTS: The effect of vibration was assessed by comparing cell
      proliferation and release of interleukin-8 (IL-8; measured by enzyme-linked
      immunosorbent assay) in cells subjected to the vibratory stimulus (both when
      treated and untreated with MAPK inhibitors) and in controls. Application of
      vibration up to 24 hours did not significantly modify cell proliferation. By
      contrast, the concentration of IL-8 in the supernatant was significantly
      increased after 12 hours and 24 hours of vibration. The inhibition of the p38,
      MEK1/2, and JNK MAPK pathways significantly reduced the overexpression of IL-8
      resulting from the vibration stimulus. CONCLUSIONS: A mechanical vibration
      simulating snoring triggered an inflammatory cascade, as reflected by the
      increase in IL-8 release mediated by MAPK pathways. The novel model developed is
      potentially applicable to studying the effects of the vibration due to snoring in
      the different cell types (epithelial, endothelial, muscular, neuronal) involved
      in airway pathophysiology during respiratory sleep disturbances.

PMID- 16295218
TI  - Self-help treatment for insomnia: a randomized controlled trial.
AB  - STUDY OBJECTIVES: Insomnia is a prevalent health complaint that often remains
      untreated. Several interventions are efficacious but they are not widely
      available. This study evaluated the efficacy of a self-help behavioral
      intervention for insomnia. DESIGN: The study used a 2 (conditions; self-help
      treatment, no treatment control) x 3 (assessments; pretreatment, posttreatment, 6
      month follow-up) mixed factorial design. SETTING: This study was part of a larger
      epidemiologic study conducted with a randomly selected sample of 2001 adults of
      the province of Quebec in Canada. PARTICIPANTS: One-hundred ninety-two adults (n
      = 127 women, 65 men; mean age, 46 years) with insomnia, selected from a larger
      community-based epidemiologic sample, were randomly assigned to self-help
      treatment (n = 96) or no-treatment control (n = 96). INTERVENTIONS: The self-help
      intervention included 6 educational booklets mailed weekly to participants and
      providing information about insomnia, healthy sleep practices, and behavioral
      sleep scheduling and cognitive strategies. MEASUREMENTS AND RESULTS: Participants
      completed sleep diaries and questionnaires at pretreatment, posttreatment, and 6
      month follow-up. Significant but modest improvements were obtained on subjective
      sleep parameters for treatment but not control participants. Treated participants
      averaged nightly gains of 21 minutes of sleep and a reduction of 20 minutes of
      wakefulness, with a corresponding increase of 4% in sleep efficiency.
      Improvements were also obtained on measures of insomnia severity (Insomnia
      Severity Index) and of sleep quality (Pittsburgh Sleep Quality Index), and those
      changes were maintained at follow-up. CONCLUSIONS: A self-help behavioral
      intervention was effective in alleviating a broad range of insomnia
      symptomatology in a community sample. Self-help may be a promising approach to
      make effective intervention more widely available.

PMID- 16295219
TI  - Impact of insomnia on individual health dissatisfaction in Japan, South Korea,
      and Taiwan.
AB  - STUDY OBJECTIVES: This study assessed the impact of insomnia on individual health
      dissatisfaction in Japan, South Korea, and Taiwan. DESIGN: Cross-sectional
      surveys with a face-to-face interview were conducted in Japan (n = 1414), South
      Korea (n = 1007), and Taiwan (n = 785). Participants completed a questionnaire on
      general health dissatisfaction and insomnia symptoms. Insomnia was defined as
      having at least one of three types of insomnia symptoms (i.e., difficulty
      initiating sleep, difficulty maintaining sleep, and early-morning awakening).
      Information on sociodemographic characteristics (i.e., sex, age, education level,
      and household income) was also collected. SETTING: N/A. PARTICIPANTS: A
      nationwide sample of subjects aged 20 years or older INTERVENTIONS: N/A.
      MEASUREMENTS AND RESULTS: The age-adjusted prevalence of insomnia "lasting more
      than 2 weeks" was 4.0% in Japan, 9.9% in South Korea, and 10.3% in Taiwan.
      Insomnia was an independent contributor to health dissatisfaction after adjusting
      for sociodemographic characteristics in the three countries, with odds ratios of
      2.54 (95% CI, [1.51-4.28]) in Japan, 2.15 (95% CI [1.33-3.48]) in South Korea,
      and 2.31 (95%CI [1.37-3.89]) in Taiwan. A multivariate logistic analysis showed
      that the sociodemographic characteristics that significantly influenced health
      dissatisfaction varied among nations-including older age and low education level
      in Japan and female gender and middle-income level in South Korea. No independent
      variables were selected in Taiwan. CONCLUSION: Insomnia is closely linked to
      health dissatisfaction in the three Asian countries, with variation according to
      social and demographic factors.

PMID- 16295220
TI  - Laryngeal and velopharyngeal sensory impairment in obstructive sleep apnea.

PMID- 16295221
TI  - Autism: acknowledging the heritable aspects of illness as possible barriers to
      successfully marshaling family assistance.

PMID- 16295222
TI  - Nosocomial pneumonia and oral health.
AB  - This article will critically review the evidence linking pneumonia to the
      aspiration of microbe-laden oropharyngeal secretions and tie that to the
      predisposition for these processes to affect dependent, medically compromised
      individuals. The goal of this review is to alert the reader to the role that oral
      disease and oral health play in fostering and preventing, respectively,
      widespread and potentially fatal pulmonary disease among high-risk individuals.

PMID- 16295223
TI  - Effect of reinforced laryngeal mask airway or endotracheal intubation anesthesia
      on adverse events: quality of life issues for dental patients requiring general
      sedation.
AB  - This study tested whether the use of a reinforced laryngeal mask airway (LMA)
      compared to endotracheal intubation (El) anesthesia diminished adverse events and
      improved the post-operative quality of life for 146 dental patients who required
      general anesthesia due to developmental disabilities. In this randomized,
      crossover trial, patients received either reinforced LMA or El anesthesia during
      an initial dental treatment visit; the other anesthetic method was used during a
      second visit scheduled after six months or more. Data were assessed with
      Student's t-test, chi-square test and McNemar's test to evaluate the affect on
      quality of life by analyzing disturbances in daily activity, such as eating
      patterns and sleeping behaviors after the procedure. Although the reinforced LMA
      anesthesia was associated with a significantly lowered incidence of adverse
      events (p = .04), neither method significantly disturbed quality of life
      activities.

PMID- 16295224
TI  - Anterior dental extractions among Dinka and Nuer refugees in the United States: a
      case series.
AB  - Few U.S. adults today experience life without permanent anterior teeth and know
      little about how an incomplete anterior dentition affects adult well-being.
      Sudanese refugees, who had resettled in the U.S. and who had six mandibular
      anterior teeth ritually extracted during youth, provided an opportunity to
      examine the significance of the effect of this partial edentulism. The authors
      interviewed five adult refugees whose anterior dentition was restored using
      dental implants. Factors considered before and after restoration included incisal
      ability, food item recognition, food consumption patterns and related social
      factors. Before restoration of the anterior dentition, participants could not
      incise typical foods eaten in the U.S. and expressed embarrassment about their
      dental status, which limited smiling, speaking and social interaction. This case
      series offers insight into the bio-cultural importance of the anterior dentition
      for all populations living with a visible gap in the lower jaw.

PMID- 16295225
TI  - Perceived need for dental care among dentate older individuals in Sri Lanka.
AB  - The authors assessed the perceived need for dental care among 585 older
      individuals, of whom 235 received a clinical oral examination. Of the 235
      participants, only 171 were dentate. The present analysis is limited to this
      group. Of these 171 dentate adults, 43 percent perceived a need for dental care.
      Of this sample section, 53 percent perceived a need for dentures. Age, perceived
      oral health status, presence of mobile teeth, three impact items of the Oral
      Health Impact Profile-14 (OHIP-14) scale--namely "had a painful aching in the
      mouth, had difficulty in eating and that the diet had been unsatisfactory due
      problems with teeth, mouth or dentures"--and the total OHIP-14 score showed
      significant associations with perceived need for dental care in bi-variate
      analysis. Poor perceived oral health status emerged as the strongest predictor of
      perceived need for dental care in logistic regression.

PMID- 16295226
TI  - Trigeminal neuralgia with intraoral trigger points: report of two cases.
AB  - A variety of pathologic conditions can cause orofacial pain. Establishing the
      etiology of the pain is key to providing appropriate treatment. Trigeminal
      neuralgia (TN) is a relatively uncommon condition and can present a diagnostic
      challenge to even the experienced dental practitioner. The authors discuss two
      cases of TN that exhibited intraoral trigger points, which initially resulted in
      confusion regarding the establishment of a correct diagnosis and treatment.

PMID- 16295227
TI  - Prevention of habitual cheek biting: a case report.
AB  - Oral and peri-oral structures can be traumatized by self-injurious behavior
      (SIB). Various articles have described prostheses used to prevent SIB-related
      injuries to the oral tissues of patients who have developmental or medical
      problems, such as psychological problems, congenital syndromes or mental
      retardation; however, reports of oral SIB in individuals unaffected by the above
      conditions are scarce. This case report describes the use of a removable
      prosthesis to prevent a stress-induced cheek biting habit in 15-year-old girl who
      did not have any of the commonly related conditions. The report discusses the
      importance of designing a prosthesis that protects tissues, while considering
      injury severity and the patient's healthas well as her ability to cooperate with
      treatment.

PMID- 16295229
TI  - The current status of hearing care: can we change the status quo?
AB  - The members of the profession of audiology often express concern that the
      services and products that have been developed to provide benefit to the hearing
      impaired are not sought after or delivered to the majority of those diagnosed
      with hearing loss. A critical look at the status quo of hearing care delivery in
      the United States is needed to verify this assumption and to develop strategies
      to improve the situation. A key concern is the lack of a comprehensive high
      quality scientific database upon which to build continuous improvements in the
      effectiveness of the services and products that are provided to the hearing
      impaired.

PMID- 16295228
TI  - Evidence-based practice in audiology.

PMID- 16295230
TI  - Evidence-based practice in provision of amplification.
AB  - Evidence-based practice (EBP) has been widely embraced in many health-care fields
      as a way of maintaining currency of knowledge and state-of-the-art treatment
      recommendations in an age of information abundance and rapid scientific progress.
      Although the principles of EBP are slowly entering the specialties of
      communication disorders, they are not well known or extensively employed as yet.
      In this article, the rationale for EBP is presented and differences between EBP
      and traditional practice are highlighted. The five-step process of EBP is
      described: defining the problem, searching for evidence, critically appraising
      the evidence, formulating a recommendation, and assessing the outcome. Critical
      appraisal calls for determination of the validity, clinical significance, and
      applicability of evidence. Each of these topics is explored with emphasis placed
      on the application of EBP to hearing rehabilitation. Finally some suggestions are
      offered for researchers and practitioners to facilitate a transition to EBP in
      amplification provision.

PMID- 16295231
TI  - Fitting hearing aids using clinical prefitting speech measures: an evidence-based
      review.
AB  - A systematic review of the literature addressed the question "Is there evidence
      of a good correlation between unaided prefitting speech measures and aided
      satisfaction on self-report measures?" This restricted question is only one of
      several possible questions related to speech measures and hearing aid fittings.
      The levels of evidence that were accepted included meta-analyses, randomized
      controlled trials, and nonrandomized intervention studies. Nearly 300 articles
      and book chapters were identified during the initial search; 220 were eliminated
      on the basis of their abstracts; and 80 papers and book chapters were reviewed in
      depth. Five studies met the criteria set forth in this review. No significant
      correlation between traditional unaided prefitting speech measures and aided
      satisfaction was found in any of the five studies. One of the studies showed a
      correlation between the results of a prefitting speech-in-noise test and self
      reported aided satisfaction.

PMID- 16295232
TI  - Fitting hearing aids to adults using prescriptive methods: an evidence-based
      review of effectiveness.
AB  - The use of a prescriptive fitting approach for hearing aid selection has been a
      common practice for the past 60-70 years. While there are prescriptive approaches
      that have been validated, in recent years it has become popular to deviate from
      these validated methods and use manufacturers' proprietary algorithms, which in
      many cases are significantly different. This research review was designed to
      examine if there was evidence supporting the use of specific gain requirements
      for hearing aid fitting. Specifically, the question that was asked was "Are there
      real-world outcome measures from adult patients that show a preference for the
      gain prescribed by a specific prescriptive fitting procedure?" Inclusion criteria
      were as follows: adult subjects, consistent technology (e.g., different
      prescriptive methods compared using same hearing aids), real-ear verification of
      gain, and real-world outcome measures. For this review, in addition to subjective
      responses, preferred use gain was considered a real-world outcome measure. The
      National Acoustic Laboratories' revised (NAL-R), revised for severe/profound (NAL
      RP), and the National Acoustic Laboratories-Non-Linear 1 (NAL-NL1) prescriptive
      methods were used as a common reference, as they have been the most commonly
      studied methods with adults. Eleven studies were identified that met the
      inclusion criteria. Eight of the studies supported gain similar to that
      prescribed by the NAL-R or NAL-RP methods; three studies supported prescribed
      gain less than the NAL-R or NAL-RP. There was no evidence that gain greater than
      that prescribed by the NAL methods should be used. The level of evidence was
      moderate, as the supporting studies were either Level 2 or Level 4, and the
      statistical power of the studies was low.

PMID- 16295233
TI  - Fitting hearing aids using clinical measures of loudness discomfort levels: an
      evidence-based review of effectiveness.
AB  - Clinical measurement of the loudness discomfort level (LDL) historically has been
      part of the hearing aid fitting procedure, and this clinical practice remains
      popular today. LDL measurements also are recommended in contemporary hearing aid
      fitting protocols. Yet, surveys show that many hearing aid users are dissatisfied
      with the loudness of their hearing aids. In this evidence-based review article,
      we evaluate the effectiveness of clinical LDL measurements. Specifically, we
      asked the question "Are the clinical measurements of LDL for adult patients
      predictive of aided acceptance and satisfaction of loudness for high inputs in
      the real world?" Nearly 200 articles were reviewed; three met the criteria set
      forth in this review. The evidence supported using unaided LDLs for selecting the
      maximum real-ear output of hearing aids. No study using aided LDLs or aided
      loudness verification met the criteria. The level of the evidence for the three
      articles using unaided LDLs was low; no higher than Level 4. The limited number
      of studies, the level of evidence, and the statistical power of the studies
      prevents us from making a strong recommendation concerning the clinical use of
      LDL measures. Additional research in this area, especially research employing
      randomized controlled trials would be a useful addition to this body of
      literature.

PMID- 16295234
TI  - Effectiveness of directional microphones and noise reduction schemes in hearing
      aids: a systematic review of the evidence.
AB  - A systematic review of the literature was undertaken to find evidence of real
      world effectiveness of directional microphone and digital noise reduction
      features in current hearing aids. The evidence was drawn from randomized
      controlled trials, nonrandomized intervention studies, and descriptive studies.
      The quality of each study was evaluated for factors such as blinding, power of
      statistical analyses, and use of psychometrically strong outcome measures.
      Weaknesses in the identified studies included small sample size, resultant poor
      power to detect potentially worthwhile differences, and overlapping experimental
      conditions. Nine studies were identified for directional microphones, and the
      evidence (albeit weak) supports effectiveness. Two studies were identified for
      the noise reduction feature, and the evidence was equivocal. For the researcher,
      such a systematic review should encourage the careful consideration of
      appropriate methodologies for assessing feature effectiveness. For the clinician,
      the outcomes reported herein should encourage use of such a systematic review to
      drive clinical practice.

PMID- 16295235
TI  - Effectiveness of counseling-based adult group aural rehabilitation programs: a
      systematic review of the evidence.
AB  - A systematic evidence-based review was conducted to examine the effectiveness of
      counseling and communication strategy-oriented group adult aural rehabilitation
      (AR) programs. The literature search for relevant articles focused on studies
      that (1) employed adults with hearing impairment; (2) used a group aural
      rehabilitation program that emphasized counseling and communication strategies;
      (3) utilized a randomized controlled trial, quasi-experimental, or non
      intervention cohort design; (4) employed an outcome measure that assessed some
      aspect of personal adjustment, perceived hearing handicap, or hearing aid benefit
      and/or satisfaction; and (5) were published in a refereed journal. Twelve
      articles were found that met these inclusion criteria. Analysis of the 12 studies
      led to the following conclusion: there is reasonably good evidence that
      participation in an adult AR program provides short-term reduction in self
      perception of hearing handicap and potentially better use of communication
      strategies and hearing aids. It is less clear whether this advantage over
      provision of hearing aids alone persists over time.

PMID- 16295236
TI  - Efficacy of individual auditory training in adults: a systematic review of the
      evidence.
AB  - A systematic review of the literature was conducted addressing the following
      question, "Is there evidence of improvement in communication skills through
      individual auditory training in an adult hearing-impaired population?" Keywords
      and authors were used as search terms in eight major indexes, and seven textbooks
      were reviewed for related references. The level of evidence that was accepted
      included randomized controlled trials, nonrandomized controlled trials, cohort,
      and before/after designs with or without control groups. Two hundred thirteen
      articles were identified during the preliminary search with 171 of these
      eliminated by review of abstracts because they did not meet the search criteria.
      Forty-two manuscripts were reviewed, with six meeting the evidence and search
      criteria. The strengths and weaknesses of these studies are high-lighted, and the
      systematic review question is answered in light of these studies. In addition,
      elements critical to the future of auditory training research and clinical
      practice are offered.

PMID- 16295237
TI  - Effectiveness of signal processing strategies for the pediatric population: a
      systematic review of the evidence.
AB  - A systematic review of literature addressing the question "Is there evidence
      pointing to optimal signal processing for pediatric hearing aid patients?" was
      conducted. Key words and authors were used as search terms in five databases, and
      one textbook appendix was reviewed for related references. The levels of evidence
      that were accepted comprised randomized controlled trials, nonrandomized
      controlled trials, cohort, and before/after designs with or without control
      groups. Two hundred twenty-six articles were identified during the preliminary
      search with 183 of these eliminated by review of abstracts because they did not
      meet the search criteria. Forty-three manuscripts were reviewed, with eight
      meeting the evidence levels and search criteria. The strengths and weaknesses of
      these studies are highlighted, and the systematic review question is answered in
      light of these studies. There is evidence to recommend wide dynamic range
      compression signal processing for pediatric hearing aid users with mild,
      moderate, and moderately severe sensorineural hearing loss when full-time and
      consistent audibility is the goal of the hearing aid fitting. Further, there is
      evidence that audibility across a wide frequency bandwidth as well as across a
      large range of input levels is essential for pediatric hearing aid users to
      recognize critical components of the spoken language.

PMID- 16295238
TI  - Creating the evidence: lessons from cochlear implants.
AB  - This paper compares the evidence-based outcomes between cochlear implants and
      hearing aids during the past several decades. Despite many similarities, there
      are also some important differences that define the progress for the two
      disciplines. Perhaps the most significant distinction exists in terms of the
      difference between the Food and Drug Administration's treatment of hearing aids
      as Class I medical devices, while cochlear implants are defined as Class III
      devices. Another point of divergence has been the number of publications in
      archival, peer-reviewed journals; implant papers have been steadily increasing
      during the past decade, while hearing aid papers have declined during the same
      period. The impact of these differences on the past, present, and future of
      hearing aid and cochlear implant research, technology, and clinical practice is
      discussed.

PMID- 16295239
TI  - When up is down.

PMID- 16295240
TI  - Acceptable noise level, phoneme recognition in noise, and measures of auditory
      efferent activity.
AB  - Acceptable noise level (ANL) is unrelated to sentence recognition in noise but
      may be related to phoneme recognition in noise (PRN). Individual differences in
      efferent activity in medial olivocochlear bundle (MOCB) and acoustic reflex (AR)
      pathways may account for intersubject variability in ANL and PRN. Monotic and
      dichotic ANL, monotic PRN, contralateral suppression of transient evoked
      otoacoustic emissions, and ipsilateral and contralateral acoustic reflex
      thresholds were measured in 31 adults with normal hearing. Results indicate that
      monotic ANL and PRN are unrelated. Monotic and dichotic ANL are related,
      suggesting that nonperipheral factors mediate ANL. Intersubject variability in
      ANL cannot be accounted for by individual differences in MOCB or AR activation.
      Intersubject variability in PRN cannot be accounted for by individual differences
      in MOCB or contralateral AR activation. It may be influenced by the ipsilateral
      AR pathway. Efferent activity in the contralateral AR arc is correlated with
      efferent activity in the MOCB.

PMID- 16295241
TI  - Absent or elevated middle ear muscle reflexes in the presence of normal
      otoacoustic emissions: a universal finding in 136 cases of auditory
      neuropathy/dys-synchrony.
AB  - We extracted a subpopulation of 136 patients (from our database of 257 AN/AD
      subjects) in whom middle ear muscle reflexes had been measured. None showed
      normal reflexes at all frequencies tested. Only three subjects showed any
      reflexes at 95 dB HL or below, but never at both 1 and 2 kHz in both ears whether
      ipsilaterally or contralaterally elicited. All the other reflex measures in these
      remaining 133 patients were either absent or observed above 100 dB HL, which is
      incongruous with their normal otoacoustic emissions throughout the frequency
      bands. Therefore, we urge colleagues to test ipsilateral middle ear muscle reflex
      at least at 1 kHz and 2 kHz in any perinatal hearing screening that depends
      solely on otoacoustic emissions. If the emissions are present and the reflexes
      are absent or elevated, an ABR may be required to properly intervene, because the
      management of AN/AD patients often differs drastically from what the behavioral
      audiogram or the ABR suggest.

PMID- 16295242
TI  - Comparison of children's performance on four tests of temporal resolution.
AB  - This paper presents a brief review of temporal processing, its relevance to
      audiologists, and methods for its clinical evaluation. Results are then
      summarized from the administration of four tests of auditory temporal resolution
      (Auditory Fusion Test-Revised [AFTR], Random Gap Detection Test [RGDT], Binaural
      Fusion Test [BFT], and Gaps-In-Noise Test [GIN]) to ten children with normal
      hearing (mean age = 8.7 years). Statistically significant differences in mean
      temporal resolution thresholds derived from the four tests resulted from
      differences in stimulus and task variables. From a clinical perspective, however,
      all tests yielded comparable results, indicating normal temporal resolution for
      all 10 children. Differences among the four tests with regard to ease of use,
      time required for administration and scoring, and face validity are discussed.
      Additional research is needed to determine the relative sensitivity and
      specificity, and, therefore, the clinical utility of these four temporal
      resolution tests in both pediatric and adult populations.

PMID- 16295243
TI  - P1 latency as a biomarker for central auditory development in children with
      hearing impairment.
AB  - We used the latency of the P1 cortical auditory-evoked potential (CAEP) as a
      biomarker for the development of central auditory pathways in three children who
      received intervention through hearing aids and/or cochlear implants. Our goal was
      to examine the clinical feasibility of using the latency of the P1 CAEP as an
      objective tool to evaluate whether acoustic amplification for hearing-impaired
      children has provided sufficient stimulation for normal development of central
      auditory pathways. If clinicians have such a marker, then they can more
      confidently make a decision about whether to provide a child with a cochlear
      implant following an appropriate hearing-aid trial. Using the same marker,
      clinicians will also be able to monitor the maturation of central auditory
      pathways once electrical stimulation is initiated.

PMID- 16295244
TI  - Unilateral versus bilateral amplification for adults with impaired hearing.
AB  - This study compared unilateral and bilateral aided speech recognition in
      background noise in 28 patients being fitted with amplification. Aided QuickSIN
      (Quick Speech-in-Noise test) scores were obtained for bilateral amplification and
      for unilateral amplification in each ear. In addition, right-ear directed and
      left-ear directed recall on the Dichotic Digits Test (DDT) was obtained from each
      participant. Results revealed that the vast majority of patients obtained better
      speech recognition in background noise on the QuickSIN from unilateral
      amplification than from bilateral amplification. There was a greater tendency for
      bilateral amplification to have a deleterious effect among older patients. Most
      frequently, better aided QuickSIN performance was obtained in the right ear of
      participants, despite similar hearing thresholds in both ears. Finally, patients
      tended to perform better on the DDT in the ear that provided less SNR loss on the
      QuickSIN. Results suggest that bilateral amplification may not always be
      beneficial in every daily listening environment when background noise is present,
      and it may be advisable for patients wearing bilateral amplification to remove
      one hearing aid when difficulty is encountered understanding speech in background
      noise.

PMID- 16295245
TI  - Validity, internal consistency, and test/retest reliability of a localization
      disabilities and handicaps questionnaire.
AB  - Psychometric evaluations were performed on a self-perceived localization
      disabilities and handicaps questionnaire. Twenty individuals with normal hearing
      bilaterally, twenty with profound unilateral hearing impairment (UHI), and ten
      with any degree of bilateral hearing impairment participated. Each subject
      completed the questionnaire. Comparisons of the responses of the subjects with
      normal hearing and those with UHI revealed significant differences among the
      groups for both disabilities and handicaps, establishing construct validity.
      Cronbach's Alpha correlational analyses of the responses of all subjects with
      hearing impairment revealed correlations of .900 (disabilities) and .800
      (handicaps), establishing internal consistency. Each participant with hearing
      impairment was asked to complete the questionnaire again after three weeks.
      Pearson's correlational analyses of the responses at time one versus time two
      revealed correlations of .900 (disabilities) and .700 (handicaps), establishing
      test/retest reliability. This questionnaire is an appropriate tool for
      investigating the self-perceived localization disabilities and handicaps of
      individuals with hearing impairment.

PMID- 16295246
TI  - An unusual case of otitis media.
AB  - This case report of bilateral otitis media in a 39-year-old woman secondary to
      Wegener's Granulomatosis highlights, for the audiologist, the importance of being
      aware of some of the less common etiologies of middle ear disease. Bilateral
      otitis media that resists usual forms of medical treatment may represent one of
      the earliest signs of Wegener's Granulomatosis, a potentially life-threatening
      disease. According to recent literature, involvement of the ears, nose, and
      throat can in many instances be the only early manifestation of the disease. It
      is important that audiologists be aware of the early signs in order to make
      appropriate referral for treatment, particularly since they are usually among the
      first to see these patients. Early diagnosis and referral is critical since the
      mean survival of untreated WG is five months, with 82% of patients dying within
      one year, and more than 90% dying within two years. The disease involves a
      systemic vasculitis that may involve any organ system: however, pulmonary or
      renal disease appear to be among the later signs, while both middle ear and upper
      respiratory involvement are frequently among the earliest.

PMID- 16295247
TI  - A clinical perspective on cochlear dead regions: intelligibility of speech and
      subjective hearing aid benefit.
AB  - Using the threshold equalizing noise (TEN) test, 49 subjects with at least two
      pure-tone thresholds per ear greater than 50 dB HL and none greater than 80 dB HL
      were evaluated for the presence or absence of dead regions. The purpose of this
      study was to (1) assess the prevalence of cochlear dead regions in this clinical
      population, (2) measure whether listeners with dead regions performed differently
      than listeners without dead regions on a speech intelligibility in noise test,
      and (3) determine whether cochlear dead regions are associated with reduced
      subjective hearing aid performance. The results showed that (1) twenty-nine
      percent of the subjects tested positive for dead regions, (2) listeners with dead
      regions had poorer sentence understanding in noise than listeners without dead
      regions and (3) listeners with dead regions perceived poorer subjective hearing
      aid performance in listening environments with reverberation or background noise
      as compared to those without dead regions.

PMID- 16295248
TI  - The effects of expansion time constants on the objective performance of hearing
      instrument users.
AB  - The present study investigated the effects of expansion time constants on the
      objective performance of 20 hearing instrument users fitted binaurally with
      digital in-the-ear products. Objective performance was evaluated in quiet using
      the Connected Speech Test and in noise using the Hearing in Noise Test. Results
      indicated that objective performance in quiet and in noise decreased as the
      expansion time constant increased. Furthermore, expansion time constants affected
      the objective performance of listeners with varying degrees of hearing loss in a
      similar manner.

PMID- 16295249
TI  - Word recognition in multitalker babble measured with two psychophysical methods.
AB  - The purpose of this experiment was to determine the relationship between
      psychometric functions for words presented in multitalker babble using a
      descending presentation level protocol and a random presentation level protocol.
      Forty veterans (mean = 63.5 years) with mild-to-moderate sensorineural hearing
      losses were enrolled. Seventy of the Northwestern University Auditory Test No. 6
      words spoken by the VA female speaker were presented at seven signal-to-babble
      ratios from 24 to 0 dB (10 words/step). Although the random procedure required 69
      sec longer to administer than the descending protocol, there was no significant
      difference between the results obtained with the two psychophysical methods.
      There was almost no relation between the perceived ability of the listeners to
      understand speech in background noise and their measured ability to understand
      speech in multitalker babble. Likewise, there was a tenuous relation between pure
      tone thresholds and performance on the words in babble and between recognition
      performance in quiet and performance on the words in babble.

PMID- 16295250
TI  - Rethinking the ethics of research.

PMID- 16295251
TI  - Reconciling protection with scientific progress.

PMID- 16295252
TI  - Conscientious autonomy: what patients do vs. what is done to them.

PMID- 16295253
TI  - Conscientious autonomy: what patients do vs. what is done to them.

PMID- 16295254
TI  - Conscientious autonomy: what patients do vs. what is done to them.

PMID- 16295255
TI  - Conscientious autonomy: what patients do vs. what is done to them.

PMID- 16295257
TI  - The negative Constitution: the duty to protect.

PMID- 16295256
TI  - Indiscretions.

PMID- 16295258
TI  - Should the gold rule? Assessing "equivalent protections" for research
      participants across international borders.

PMID- 16295259
TI  - Shouldering the burden of care.

PMID- 16295260
TI  - Clarifying confusions about coercion.

PMID- 16295261
TI  - Making research a requirement of treatment: why we should sometimes let doctors
      pressure patients to participate in research.
AB  - When a patient could be offered one of multiple established treatments, doctors
      should be able to offer treatment only if the patient agrees to participate in
      research aimed at determining which of the treatments is most effective. Making
      treatment conditional on research participation will help researchers complete
      badly needed studies.

PMID- 16295262
TI  - A closer look at the bad deal trial: beyond clinical equipoise.
AB  - Some commentators have recently proposed that "clinical equipoise," although
      widely accepted, is not necessary for morally acceptable research on human
      subjects. If this concept is rejected, however, we may find that trials not in
      the best medical interests of their subjects--"bad deal trials"--could be
      justified. To avoid exploiting participants, we must find a way to distribute the
      risks fairly, even if it means embracing radical changes in the way clinical
      research is conducted.

PMID- 16295263
TI  - Protecting subjects who cannot give consent: toward a better standard for
      "minimal" risks.
AB  - When children and incapacitated adults are enrolled in research that cannot
      directly benefit them, they can be exposed to no more than "minimal" risks,
      according to guidelines accepted around the world. We need a new standard for
      what "minimal" risks are, however--one that recognizes that participating in non
      beneficial research is like participating in a charitable activity. Such a
      standard appears likely to provide more stringent protections for these
      vulnerable populations.

PMID- 16295265
TI  - Nanoparticles and the environment.

PMID- 16295264
TI  - Do researchers learn to overlook misbehavior?

PMID- 16295266
TI  - Relative importance of school bus-related microenvironments to children's
      pollutant exposure.
AB  - Real-time concentrations of black carbon, particle-bound polycyclic aromatic
      hydrocarbons, nitrogen dioxide, and fine particulate counts, as well as
      integrated and real-time fine particulate matter (PM2.5) mass concentrations were
      measured inside school buses during long commutes on Los Angeles Unified School
      District bus routes, at bus stops along the routes, at the bus loading/unloading
      zone in front of the selected school, and at nearby urban "background" sites.
      Across all of the pollutants, mean concentrations during bus commutes were higher
      than in any other microenvironment. Mean exposures (mean concentration times time
      spent in a particular microenvironment) in bus commutes were between 50 and 200
      times greater than those for the loading/unloading microenvironment, and 20-40
      times higher than those for the bus stops, depending on the pollutant. Although
      the analyzed school bus commutes represented only 10% of a child's day, on
      average they contributed one-third of a child's 24-hr overall black carbon
      exposure during a school day. For species closely related to vehicle exhaust, the
      within- cabin exposures were generally dominated by the effect of surrounding
      traffic when windows were open and by the bus's own exhaust when windows were
      closed. Low-emitting buses generally exhibited high concentrations only when
      traveling behind a diesel vehicle, whereas high-emitting buses exhibited high
      concentrations both when following other diesel vehicles and when idling without
      another diesel vehicle in front of the bus. To reduce school bus commute
      exposures, we recommend minimizing commute times, avoiding caravanning with other
      school buses, using the cleanest buses for the longest bus routes, maintaining
      conventional diesel buses to eliminate visible emissions, and transitioning to
      cleaner fuels and advanced particulate control technologies as soon as possible.

PMID- 16295267
TI  - A modal approach to vehicular emissions and fuel consumption model development.
AB  - This study reports on the analysis of emissions and fuel consumption from motor
      vehicles using a modal approach. The four standard driving modes are idling,
      accelerating, cruising, and decelerating. On-road data were collected using
      instrumented test vehicles traveling many times through the urban areas of Hong
      Kong. A model was developed for estimating vehicular fuel consumption and
      emissions as a function of instantaneous speed and driving mode. Piecewise
      interpolation functions were proposed for each nonidling driving mode. Idling
      emission and fuel consumption rates were estimated as negative exponential
      functions of idling time. Preliminary modeling results showed good agreements for
      the test vehicles and indicated that the on-road measurements are feasible for
      the development of modal emission and fuel consumption models.

PMID- 16295268
TI  - Evaluating speed differences between passenger vehicles and heavy trucks for
      transportation-related emissions modeling.
AB  - Heavy-duty trucks make up only 3% of the on-road vehicle fleet, yet they account
      for > 7% of vehicle miles traveled in the United States. They also contribute a
      significant proportion of regulated ambient emissions. Heavy vehicles emit
      emissions at different rates than passenger vehicles. They may also behave
      differently on-road, yet may be treated similarly to passenger vehicles in
      emissions modeling. Input variables to the MOBILE software, such as average
      vehicle speed, are typically specified the same for heavy trucks as for passenger
      vehicles. Although not frequently considered in modeling emissions, speed
      differences between passenger vehicles and heavy trucks may influence emissions,
      because emission rates are correlated to average speed. Differences were
      evaluated by collecting average and spot speeds for heavy trucks and passenger
      vehicles on arterials and spot speeds on freeways in Des Moines, IA, and
      Minneapolis/St. Paul, MN. Speeds were compared by study site. Space mean speeds
      for heavy trucks were lower than passenger vehicle speeds for all of the
      arterials with differences ranging from 0.8 to 19 mph. Spot speeds for heavy
      trucks were also lower at all of the arterial and freeway locations with
      differences ranging from 0.8 to 6.1 mph. The impact that differences in on-road
      speeds had on emissions was also evaluated using MOBILE version 6.2.
      Misspecification of average truck speed is the most significant at lower and
      higher speed ranges.

PMID- 16295269
TI  - Temperature dependence of nickel stabilization in inorganic oxide matrices.
AB  - Scanning electron microscopy, X-ray diffractometry, X-ray absorption
      spectroscopy, and other means are used to investigate the effect of thermal
      treatment temperature, 105-1100 degrees C, on the immobilization of nickel (Ni)
      by the inorganic oxides of latosol. Ni is more firmly immobilized by the latosol
      with increasing temperature. Spectral analyses indicate that a shoulder toward
      the edge-jump appears in the spectra of X-ray absorption near-edge structure for
      the samples heated at 900 and 1100 degrees C. Moreover, the intensity of the main
      peak at the edge increases with higher temperature; this information indicates
      the distortion of the divalent nickel [Ni(II)] environment in the samples heated
      at 900 and 1100 degrees C. Nevertheless, the distortion is absent from the
      samples heated at 105 and 500 degrees C. The fact of the distortion of the Ni(II)
      environment suggests the occurrence of a chemical reaction between the Ni
      compound and the inorganic matrices of the latosol soil during the heating
      process at 900 and 1100 degrees C. In addition, the extended X-ray absorption
      fine structure results correspond well to the X-ray absorption near-edge
      structure results; the former are supportive of the occurrence of a distorted
      Ni(II) environment in the samples heated at 900 and 1100 degrees C. The wet
      chemistry results show that the samples heated at 900-1100 degrees C leach less
      Ni than the 105-500 degrees C samples do. The change of the Ni environment is
      related to the observation that less Ni is leached from the samples heated at 900
      1100 degrees C. Furthermore, the pore closing phenomenon is observed only in the
      1100 degrees C sample; this phenomenon corresponds with the fact that the 1100
      degrees C sample leaches less Ni than the 900 degrees C sample does.

PMID- 16295270
TI  - Improving source apportionment of fine particles in the eastern United States
      utilizing temperature-resolved carbon fractions.
AB  - The objectives of this study were to examine the use of carbon fractions to
      identify particulate matter (PM) sources, especially traffic-related carbonaceous
      particle sources, and to estimate their contributions to the particle mass
      concentrations. In recent studies, positive matrix factorization (PMF) was
      applied to ambient fine PM (PM2.5) compositional data sets of 24-hr integrated
      samples including eight individual carbon fractions collected at three monitoring
      sites in the eastern United States: Atlanta, GA, Washington, DC, and Brigantine,
      NJ. Particulate carbon was analyzed using the Interagency Monitoring of Protected
      Visual Environments/Thermal Optical Reflectance method that divides carbon into
      four organic carbons (OC): pyrolized OC and three elemental carbon (EC)
      fractions. In contrast to earlier PMF studies that included only the total OC and
      EC concentrations, gasoline emissions could be distinguished from diesel
      emissions based on the differences in the abundances of the carbon fractions
      between the two sources. The compositional profiles for these two major source
      types show similarities among the three sites. Temperature-resolved carbon
      fractions also enhanced separations of carbon-rich secondary sulfate aerosols.
      Potential source contribution function analyses show the potential source areas
      and pathways of sulfate-rich secondary aerosols, especially the regional
      influences of the biogenic, as well as anthropogenic secondary aerosol. This
      study indicates that temperature-resolved carbon fractions can be used to enhance
      the source apportionment of ambient PM2.5.

PMID- 16295271
TI  - Potential interference bias in ozone standard compliance monitoring.
AB  - The U.S. Environmental Protection Agency has established a federal reference
      method (FRM) for ozone (O3) and allowed for designation of federal equivalent
      methods (FEMs). However, the ethylene-chemiluminescence FRM for O3 has been
      replaced by the UV photometric FEM by most state and local monitoring agencies
      because of its relative ease of operation. Accumulating evidence indicates that
      the FEM is prone to bias under the hot, humid, and stagnant conditions conducive
      to high O3 formation. This bias may lead to overreporting hourly O3
      concentrations by as much as 20-40 ppb. Measurement bias is caused by
      contamination of the O3 scrubber, a problem that is not detected by dry air
      calibration. An adequate wet test has not been codified, although a procedure has
      been proposed for agency consideration. This paper includes documentation of
      laboratory tests quantifying specific interferant responses, collocated ambient
      FRM/FEM monitoring results, and smog chamber comparisons of the FRM and FEMs with
      alternative scrubber designs. As the numbers of reports on monitor interferences
      have grown, interested parties have called for agency recognition and correction
      of these biases.

PMID- 16295272
TI  - Consistency of ozone and nitrogen oxides standards at tropospherically relevant
      mixing ratios.
AB  - The absolute accuracy and long-term precision of atmospheric measurements hinge
      on the quality of the instrumentation and calibration standards. To assess the
      consistency of the ozone (O3) and nitrogen oxides (NO(x)) standards maintained at
      the National Institute of Standards and Technology (NIST), these standards were
      compared through the gas-phase titration of O3 with nitric oxide (NO). NO and O3
      were monitored using chemiluminescence and UV absorption, respectively. Nitrogen
      dioxide (NO2) was monitored directly by laser-induced fluorescence and indirectly
      by catalytic conversion to NO, followed by chemiluminescence. The observed
      equivalent loss of both NO and O3 and the formation of NO2 in these experiments
      was within 1% on average over the range of 40-200 nmol mol(-1) of NO in excess
      O3, indicating that these instruments, when calibrated with the NIST O3 and NO
      standards and the NO2 permeation calibration system, are consistent to within 1%
      at tropospherically relevant mixing ratios of O3. Experiments conducted at higher
      initial NO mixing ratios or in excess NO are not in as good agreement. The
      largest discrepancies are associated with the chemiluminescence measurements.
      These results indicate the presence of systematic biases under these specific
      conditions. Prospects for improving these experiments are discussed.

PMID- 16295273
TI  - High-mileage study of on-board diagnostic emissions.
AB  - The 1990 Clean Air Act amendments require the U.S. Environmental Protection
      Agency (EPA) to set guidelines for states to follow in designing and running
      vehicle inspection and maintenance (I/M) programs. Included in this charge was a
      requirement to implement an on-board diagnostic (OBD) test for both basic and
      enhanced I/M programs. This paper provides the results to date of an ongoing EPA
      study undertaken to assess the durability of the OBD system as vehicles age and
      as mileage is accrued. The primary results of this effort indicate the points
      described below. First, the majority of high-mileage vehicles tested had emission
      levels within their certification limits, and their malfunction indicator light
      (MIL) was not illuminated, indicating that the systems are capable of working
      throughout the life of a vehicle. Second, OBD provides better air quality
      benefits than an IM240 test (using the federal test procedure [FTP] as the
      benchmark comparison). This statement is based on greater emissions reductions
      from OBD-directed repairs than reductions associated with IM240-identified
      repairs. In general, the benefits of repairing the OBD fails were smaller, but
      the aggregate benefits were greater, indicating that OBD tests find both the high
      emitting and a number of marginally high-emitting vehicles without false failures
      that can occur with any tailpipe test. Third, vehicles that truly had high
      tailpipe emissions as confirmed by laboratory IM240 and FTP testing also had
      illuminated MILs at a statistically significant level. Last, field data from
      state programs have demonstrated MIL illumination rates comparable with those
      seen in this work, suggesting that the vehicles sampled in this study were
      representative of the larger fleet. Nonetheless, it is important to continue the
      testing of high-mileage OBD vehicles into the foreseeable future to ensure that
      the systems are operating correctly as the fleet ages and as changes in emission
      certification levels take effect.

PMID- 16295274
TI  - Source location and characterization of volatile organic compound emissions at a
      petrochemical plant in Kaohsiung, Taiwan.
AB  - This paper elucidated a novel approach to locating volatile organic compound
      (VOC) emission sources and characterizing their VOCs by database and contour
      plotting. The target of this survey was a petrochemical plant in Linyan,
      Kaohsiung County, Taiwan. Samples were taken with canisters from 25 sites inside
      this plant, twice per season, and analyzed by gas chromatography-mass
      spectrometry. The survey covered 1 whole year. By consolidated into a database,
      the data could be readily retrieved, statistically analyzed, and clearly
      presented in both table and graph forms. It followed from the cross-analysis of
      the database that the abundant types of VOCs were alkanes, alkenes/dienes, and
      aromatics, all of which accounted for 99% of total VOCs. By contour plotting, the
      emission sources for alkanes, aromatics, and alkenes/ dienes were successfully
      located. Through statistical analysis, the database could provide the range and
      90% confidence interval of each species from each emission source. Both alkanes
      and alkene/dienes came from tank farm and naphtha cracking units and were mainly
      composed of C3-C5 members. Regarding aromatics, benzene, toluene, and xylenes
      were the primary species; they were emitted from tank farm, aromatic units, and
      xylene units.

PMID- 16295275
TI  - Comparison of ozone temporal scales for large urban, small urban, and rural areas
      in Georgia.
AB  - Ground-level ozone (O3) time series are characterized by the sum of several
      distinct temporal scales: long-term, seasonal, synoptic, diurnal (daily), and
      intraday variation. In this study, the authors use a Kolmorogov-Zurbenko filter
      to separate the 1981-2001 O3 time-series from many sites in and around Georgia
      into these various components. The authors compare the temporal components to
      examine differences between small and large metropolitan areas and between urban
      and rural areas. They then focus on the synoptic component to define a
      predominant transport region or airshed for each site.

PMID- 16295276
TI  - Parameter evaluation and model validation of ozone exposure assessment using
      Harvard Southern California Chronic Ozone Exposure Study data.
AB  - To examine factors influencing long-term ozone (O3) exposures by children living
      in urban communities, the authors analyzed longitudinal data on personal, indoor,
      and outdoor O3 concentrations, as well as related housing and other questionnaire
      information collected in the one-year-long Harvard Southern California Chronic
      Ozone Exposure Study. Of 224 children contained in the original data set, 160
      children were found to have longitudinal measurements of O3 concentrations in at
      least six months of 12 months of the study period. Data for these children were
      randomly split into two equal sets: one for model development and the other for
      model validation. Mixed models with various variance-covariance structures were
      developed to evaluate statistically important predictors for chronic personal
      ozone exposures. Model predictions were then validated against the field
      measurements using an empirical best-linear unbiased prediction technique. The
      results of model fitting showed that the most important predictors for personal
      ozone exposure include indoor O3 concentration, central ambient O3 concentration,
      outdoor O3 concentration, season, gender, outdoor time, house fan usage, and the
      presence of a gas range in the house. Hierarchical models of personal O3
      concentrations indicate the following levels of explanatory power for each of the
      predictive models: indoor and outdoor O3 concentrations plus questionnaire
      variables, central and indoor O3 concentrations plus questionnaire variables,
      indoor O3 concentrations plus questionnaire variables, central O3 concentrations
      plus questionnaire variables, and questionnaire data alone on time activity and
      housing characteristics. These results provide important information on key
      predictors of chronic human exposures to ambient O3 for children and offer
      insights into how to reliably and cost-effectively predict personal O3 exposures
      in the future. Furthermore, the techniques and findings derived from this study
      also have strong implications for selecting the most reliable and cost-effective
      exposure study design and modeling approaches for other ambient pollutants, such
      as fine particulate matter and selected urban air toxics.

PMID- 16295277
TI  - Prescribed burns and wildfires in Colorado: impacts of mitigation measures on
      indoor air particulate matter.
AB  - Wildfires and prescribed burns are receiving increasing attention as sources of
      fine particulate matter (PM2.5). The goal of this research project was to
      understand the impact of mitigation strategies for residences impacted by
      scheduled prescribed burns and wildfires. Pairs of residences were solicited to
      have PM2.5 concentrations monitored inside and outside of their houses during
      four fires. The effect of using air cleaners on indoor PM2.5 was investigated, as
      well as the effect of keeping windows closed. Appropriately sized air cleaners
      were provided to one of each pair of residences; occupants of all of the
      residences were asked to keep windows shut and minimize opening of exterior
      doors. Additionally, residents were asked to record all of the activities that
      may be a source of particulate matter, such as cooking and cleaning. Measurements
      were made during one prescribed burn and three wildfires during the 2002 fire
      season. Outdoor 24-hr average PM2.5 concentrations ranging from 6 to 38 microg/m3
      were measured during the fires, compared with levels of 2-5 microg/m3 during
      background measurements when no fires were burning. During the fires, PM2.5 was <
      3 microg/m3 inside all of the houses with air cleaners installed. This
      corresponds with a decrease of 63-88% in homes with the air cleaners operating
      when compared with homes without air cleaners. In the homes without the air
      cleaners, measured indoor concentrations were 58-100% of the concentrations
      measured outdoors.

PMID- 16295278
TI  - The Southeastern Aerosol Research and Characterization Study: Part II. Filter
      based measurements of fine and coarse particulate matter mass and composition.
AB  - The Southeastern Aerosol Research and Characterization Study (SEARCH) was
      implemented in 1998-1999 to provide data and analyses for the investigation of
      the sources, chemical speciation, and long-term trends of fine particulate matter
      (PM2.5) and coarse particulate matter (PM10-2.5) in the Southeastern United
      States. This work is an initial analysis of 5 years (1999-2003) of filter-based
      PM2.5 and PM10-2.5 data from SEARCH. We find that annual PM2.5 design values were
      consistently above the National Ambient Air Quality Standards (NAAQS) 15
      microg/m3 annual standard only at monitoring sites in the two largest urban areas
      (Atlanta, GA, and North Birmingham, AL). Other sites in the network had annual
      design values below the standard, and no site had daily design values above the
      NAAQS 65 microg/m3 daily standard. Using a particle composition monitor designed
      specifically for SEARCH, we found that volatilization losses of nitrate,
      ammonium, and organic carbon must be accounted for to accurately characterize
      atmospheric particulate matter. In particular, the federal reference method for
      PM2.5 underestimates mass by 3-7% as a result of these volatilization losses.
      Organic matter (OM) and sulfate account for approximately 60% of PM2.5 mass at
      SEARCH sites, whereas major metal oxides (MMO) and unidentified components
      ("other") account for > or = 80% of PM10-2.5 mass. Limited data suggest that much
      of the unidentified mass in PM10-2.5 may be OM. For paired comparisons of urban
      rural sites, differences in PM2.5 mass are explained, in large part, by higher OM
      and black carbon at the urban site. For PM10, higher urban concentrations are
      explained by higher MMO and "other." Annual means for PM2.5 and PM10-2.5 mass and
      major components demonstrate substantial declines at all of the SEARCH sites over
      the 1999-2003 period (10-20% in the case of PM2.5, dominated by 14-20% declines
      in sulfate and 11-26% declines in OM, and 14-25% in the case of PM10-2.5,
      dominated by 17-30% declines in MMO and 14-31% declines in "other"). Although
      declining national emissions of sulfur dioxide and anthropogenic carbon may
      account for a portion of the observed declines, additional investigation will be
      necessary to establish a quantitative assessment, especially regarding trends in
      local and regional emissions, primary carbon emissions, and meteorology.

PMID- 16295279
TI  - Air quality modeling of interpollutant trading for ozone precursors in an urban
      area.
AB  - Emission trading is a market-based approach designed to improve the efficiency
      and economic viability of emission control programs; emission trading has
      typically been confined to trades among single pollutants. Interpollutant trading
      (IPT), as described in this work, allows for trades among emissions of different
      compounds that affect the same air quality end point, in this work, ambient ozone
      (O3) concentrations. Because emissions of different compounds impact air quality
      end points differently, weighting factors or trading ratios (tons of emissions of
      nitrogen oxides (NO(x)) equivalent to a ton of emissions of volatile organic
      compounds [VOCs]) must be developed to allow for IPT. In this work, IPT indices
      based on reductions in O3 concentrations and based on reductions in population
      exposures to O3 were developed and evaluated using a three-dimensional gridded
      photochemical model for Austin, TX, a city currently on the cusp of nonattainment
      with the National Ambient Air Quality Standards for O3 concentrations averaged
      over 8 hr. Emissions of VOC and NO(x) from area and mobile sources in Austin are
      larger than emissions from point sources. The analysis indicated that mobile and
      area sources exhibited similar impacts. Trading ratios based on maximum O3
      concentration or population exposure were similar. In contrast, the trading
      ratios did exhibit significant (more than a factor of two) day-to-day
      variability. Analysis of the air quality modeling indicated that the daily
      variability in trading ratios could be attributed to daily variations in both
      emissions and meteorology.

PMID- 16295280
TI  - Air quality modeling and decisions for ozone reduction strategies.
AB  - Despite the widespread application of photochemical air quality models (AQMs) in
      U.S. state implementation planning (SIP) for attainment of the ambient ozone
      standard, documentation for the reliability of projections has remained highly
      subjective. An "idealized" evaluation framework is proposed that provides a means
      for assessing reliability. Applied to 18 cases of regulatory modeling in the
      early 1990s in North America, a comparative review of these applications is
      reported. The intercomparisons suggest that more than two thirds of these AQM
      applications suffered from having inadequate air quality and meteorological
      databases. Emissions representations often were unreliable; uncertainties were
      too high. More than two thirds of the performance evaluation efforts were judged
      to be substandard compared with idealized goals. Meteorological conditions chosen
      according regulatory guidelines were limited to one or two cases and tended to be
      similar, thus limiting the extent to which public policy makers could be
      confident that the emission controls adopted would yield attainment for a broad
      range of adverse atmospheric conditions. More than half of the studies reviewed
      did not give sufficient attention to addressing the potential for compensating
      errors. Corroborative analyses were conducted in only one of the 18 studies
      reviewed. Insufficient attention was given to the estimation of model and/or
      input database errors, uncertainties, or variability in all of the cases
      examined. However, recent SIP and policy-related regional modeling provides
      evidence of substantial improvements in the underlying science and available
      modeling systems used for regulatory decision making. Nevertheless, the
      availability of suitable databases to support increasingly sophisticated modeling
      continues to be a concern for many locations. Thus, AQM results may still be
      subject to significant uncertainties. The evaluative process used here provides a
      framework for modelers and public policy makers to assess the adequacy of
      contemporary and future modeling work.

PMID- 16295281
TI  - Using RICO to fight understaffing in nursing homes: how federal prosecution using
      RICO can reduce abuse and neglect of the elderly.

PMID- 16295282
TI  - Utilization and costs of the introduction of system-wide palliative care in
      Alberta, 1993-2000.
AB  - BACKGROUND: De-institutionalization of health care services provided to
      terminally ill cancer patients is a cost-effective strategy that underpins health
      care reforms in Canada. The objective of this study therefore is to evaluate the
      economic implications associated with Canadian innovations in the delivery of
      palliative care services. METHODS: We identified 16,282 adults who died of cancer
      between 1993 and 2000 in two Canadian cities with newly introduced palliative
      care programs. Linkage of administrative databases was used to measure healthcare
      resource utilization. We sought to describe the utilization of palliative care
      services and its consequences for overall health care system costs. RESULTS: Use
      of palliative services increased from 45 to 81% of cancer patients during the
      study period. Identifiable public health care services cost dollars
      28093Cdn/patient (19033US dollars, 11,508GBl, 17,778 euro) for terminally ill
      cancer patients in their last year of life. Acute care accounted for two-thirds
      (67%) of these costs; physician (10%), residential hospice care (8%), nursing
      homes (6%), home care (6%) and prescription medications (3%) comprise the
      remainder. Increased costs associated with the introduction of palliative care
      programs were offset by cost savings realized when terminally ill cancer patients
      spent less time in hospital. Palliative home care and residential hospice care
      accounted for the bulk of this substitution effect. Cost neutrality was observed
      from the public perspective. DISCUSSION: These results demonstrate that the
      introduction of comprehensive and community-based palliative care services
      resulted in increased palliative care service delivery and cost neutrality,
      primarily achieved through a decreased use of acute care beds.

PMID- 16295283
TI  - Painful bone metastases: a prospective observational cohort study.
AB  - Incident pain related to bone metastases is a problematic symptom to treat. The
      difficulty in treating this type of pain is reflected in the wide variety of
      treatment modalities recommended. The aims of this prospective observational
      study were to determine the patterns of pain severity at rest and on movement
      over time and which treatment modalities are employed. In addition, we were
      interested in ascertaining any correlations between bone pain at rest, bone pain
      on movement and functional ability. Thirty-two patients were followed up for a
      mean of 22 weeks (range: 2-52). In total, there were 704 patient follow-up weeks.
      Patients were followed up for one year or until death. A total of 19 different
      treatment modalities were employed. There were strong correlations between pain
      at rest and pain on movement. There were no significant correlations between
      functional ability and pain at rest or movement. Our study demonstrates the
      complex management of patients with bone pain. This is the first study that
      highlights the correlation between pain at rest and pain on movement in patients
      with bone metastases in a palliative care population. It highlights the need for
      intensive follow-up of these patients, as they require multiple interventions to
      help control their pain. These data can also be used to power further
      interventional studies.

PMID- 16295284
TI  - Breaking bad news: experiences and preferences of advanced cancer patients at a
      Portuguese oncology centre.
AB  - The disclosure of information to patients about diagnosis and prognosis and other
      aspects of care is still a matter of debate. We have conducted a study in
      advanced cancer patients about their experiences and preferences concerning this
      issue. A questionnaire was developed and completed during the first appointment
      in the outpatient clinic of an oncology centre's palliative care unit, before the
      patient had any contact with the staff of the unit. The study was conducted on a
      convenience sample of 47 patients. We found that 34 (72%) of those patients
      thought they had been informed of their diagnosis, most of them by the hospital
      doctor. However, not all stated the diagnosis in a manner clearly showing that
      they were aware of the nature of their disease. Most patients were with a family
      member when the diagnosis was disclosed, which is what the majority had
      preferred. Of the 13 uninformed patients, only one preferred to remain
      uninformed. Most patients (89%) participated in decisions concerning treatment,
      although only 68% thought they should have participated. Some 39 patients (83%)
      were informed that they were being referred to the palliative care unit, but
      surprisingly only eight had received an explanation of the unit's function. We
      concluded that, although most patients had been informed of their disease, there
      remains many problems, the most important of which, in our view, is the
      difference between the information provided and the patients' needs.

PMID- 16295285
TI  - Seeking new methodology for palliative care research: challenging assumptions
      about studying people who are approaching the end of life.
AB  - Palliative care researchers face many ethical and practical challenges. In
      particular, recruitment has proven difficult. New methodologies and methods need
      to be developed if barriers are to be overcome. This paper presents an example of
      a participatory approach to research with people receiving palliative care
      services. The approach was used for recruitment into an in-depth multi-methods
      study of weight loss and eating difficulties experienced by people with advanced
      cancer. Methods included a survey of patients on the case-loads of two community
      palliative care teams working in the South of England in 2003. The questionnaire
      was returned by 199 patients, 58% of the total patient population under the care
      of the two teams. Benefits of the approach taken are detailed, but also issues
      that emerged across the course of recruitment, thus highlighting points of
      interest for palliative care researchers. It is proposed that the success of the
      recruitment process can be attributed to the adoption of a context specific
      participatory approach. Successful recruitment into the study challenges the
      widely held belief that, for practical and ethical reasons, it is inappropriate
      to study people who are approaching the end of life. It demonstrates that a
      participatory approach enables clinical practice and research to share decision
      making and values, leading to a feasible and successful recruitment process that
      is acceptable to clinicians, researchers and patients.

PMID- 16295286
TI  - Validation of the McGill Quality of Life Questionnaire in home hospice settings
      in Israel.
AB  - Given that the meaning and significance of 'quality of life' can differ among
      language and cultural groups, it is incumbent upon researchers to assess whether
      the tool they have chosen is appropriate to the population under study. This
      study aimed to test the reliability and validity of the McGill Quality of Life
      Questionnaire (MQOL) translated into Hebrew for use with palliative care patients
      in Israel. In this, as in previous studies, the 16 questions of the tool
      clustered into four domains (physical, psychological, existential well-being and
      support), although the distribution of items among them differed somewhat. The
      existential well-being and psychological domains had an independent effect on the
      overall quality of life of patients in Israel, as in other countries. It seems
      that this tool produces similar responses in metastatic cancer patients around
      the world, and hence can be used to compare palliative care services in different
      countries.

PMID- 16295287
TI  - Palliative care of patients with a primary malignant brain tumour: case review of
      service use and support provided.
AB  - Individuals with a primary malignant brain tumour require intensive palliative
      care services because of the symptoms and cognitive problems they experience.
      Many of these patients stay with their families at home, being supported by
      palliative care home teams rather than being admitted for hospice care. The
      provision of respite care and community services to support these families goes
      largely unreported. This study arises out of a need to review support services
      for patients and carers within one cancer and palliative care service. This
      retrospective case analysis identifies that there are a range of services used in
      the community to support patients with primary malignant brain tumours but that
      only a small proportion receive inpatient hospice care. District nursing services
      were extensively used but also a high number (74%) of patients were admitted to
      local hospitals for symptom management. This paper attempts to explore the
      services utilized but also questions the apparently limited provision of hospice
      care for supporting individuals in the palliative care stages of such an illness.
      This paper considers the illness trajectory, the complex symptoms experienced by
      patients and respite services utilized. Issues of those engaged in informal care
      giving and in the provision of support for those with a primary malignant glioma
      are also considered.

PMID- 16295288
TI  - Caregiving for the terminally ill: at what cost?
AB  - This literature review exposes the nature and extent of physical and psychosocial
      morbidity and economic disadvantage, home palliative caregivers suffer as a
      direct result of their caregiving role. Research has demonstrated that caregivers
      providing support to individuals receiving palliative care report unmet needs for
      information, communication, service provision and support from health and
      community services. Three sets of challenges are highlighted in this literature
      review which help explain why the needs of home palliative caregivers are largely
      unmet: (i) barriers to seeking help; (ii) a dearth of research-based
      interventions focused on reducing the negative aspects of caregiving; and (iii) a
      number of impediments to effective policy and service development for family
      caregivers. Furthermore, invited submissions from caregivers echoed and confirmed
      the issues reported in the literature. Recommendations for enhancing caregiver
      support are outlined.

PMID- 16295289
TI  - Estimating the size of a potential palliative care population.
AB  - OBJECTIVES: To develop a method for estimating the population who could
      potentially benefit from receiving palliative care in the last year of their
      lives, and then apply the estimates to the Western Australian population to
      ascertain characteristics of these people. METHODS: Three estimates of the
      potential palliative care population, Minimal, Mid-range and Maximal, were
      developed through focus groups, interviews and the literature. These estimates
      were applied to the cohort of people who died in Western Australia between 1 July
      2000 and 31 December 2002 by linking death records with hospital morbidity data
      through the Western Australian Data Linkage System. RESULTS: Between 0.28% and
      0.50% of people in the Western Australian population in any one year could
      potentially benefit from palliative care, many of whom die from conditions other
      than neoplasms. While neoplasms accounted for 59.5% of all underlying causes of
      deaths in the Minimal Estimate, heart failure (21.0%), renal failure (9.8%),
      chronic obstructive pulmonary disease (9.6%), Alzheimer's disease (4.0%), liver
      failure (3.2%), Parkinson's disease (1.3%), motor neurone disease (0.9%),
      HIV/AIDS (<0.01%) and Huntington's disease (<0.01%) accounted for other
      conditions in this estimate. The study was expanded to include Mid-range and
      Maximal Estimates. Characteristics of the Western Australian population in these
      three estimates are described. CONCLUSIONS: Unlike traditional palliative care
      estimates that focus on malignant disease, this study included nonmalignant
      conditions in a set of three estimates of a potential palliative care population.
      By using population-based data to describe characteristics of people who compose
      palliative care populations, these results offer a tool for planning equitable
      healthcare services.

PMID- 16295290
TI  - Managing patients with cancer and advanced liver disease.

PMID- 16295291
TI  - Physicians' knowledge of transdermal fentanyl.

PMID- 16295292
TI  - Physicians' knowledge of transdermal fentanyl.

PMID- 16295293
TI  - Methadone titration: still no gauge on the tank.

PMID- 16295294
TI  - Persistent hiccups after slow-release morphine.

PMID- 16295295
TI  - Cytomegalovirus osteomyelitis in a terminally ill cancer patient.

PMID- 16295297
TI  - Katrina aftermath.

PMID- 16295298
TI  - Katrina.

PMID- 16295296
TI  - Profiles of pain in Mississippi: results from the Southern Pain Prevalence Study.
AB  - OBJECTIVES: To estimate the prevalence, intensity, frequency, and origins of pain
      in Mississippi residents and explore the social and cultural aspects of pain and
      pain management by measuring the impacts of pain on everyday life as well as
      respondents' beliefs and attitudes toward pain. STUDY DESIGN: Cross-sectional
      survey of Mississippi adults. SUMMARY OF BACKGROUND DATA: Data from previous
      population surveys and clinical studies indicate that pain is a pervasive part of
      everyday life. The prevalence, intensity and frequency of reported pain is
      substantial throughout these studies. The literature documents large and profound
      consequences of pain both for individual lives and for society. The data also
      suggest that beliefs and attitudes rooted in the social and cultural context of
      society may help explain how pain is managed or endured. METHODS: Telephone
      interviews with a representative sample (random digit dialing) of 604 Mississippi
      adults were conducted utilizing a computer-assisted telephone interviewing
      system. The cooperation rate was 94.8% (5.2 % refusal). The Code of Standards and
      Ethics for Survey Research rate was 67.4% and the maximum sampling error was +/-
      4.0% (95% confidence interval). The Mississippi survey data represent a subset of
      the data obtained in the six-state Southern Pain Prevalence Study. RESULTS: The
      pain prevalence rate was estimated to be 37% of the overall Mississippi sample:
      9% of the sample reported severe pain on at least a monthly basis; 16% reported
      moderate pain; and 12% reported mild pain. Among those reporting pain, a majority
      (52%) experienced pain on a daily basis. The most commonly reported origins of
      pain were back pain (49%), leg and knee pain (41%), and shoulder.and arm pain
      (20%). Respondents also reported that both moderate and severe pain had
      substantial negative impacts on multiple facets of everyday life, including
      interference with sleep (84%), recreational/leisure activities (78%), ability to
      work (68%), sexual relations (43%), and relationships with others (36%). Mental
      health impacts for respondents with moderate to severe pain on at least a monthly
      basis included increased feelings of anxiety (66%), self-reported depression
      (63%), and loneliness (46%). When responding to questions regarding beliefs and
      attitudes about pain and pain management, the majority of respondents (62%)
      considered pain to be a normal part of everyday life. Many respondents felt that
      medicine should be saved until the pain becomes worse (55%), and a substantial
      number of respondents felt that good patients do not complain about pain to their
      doctors (22%). CONCLUSIONS: This study expands the body of knowledge about the
      prevalence of pain in Mississippi, suggesting that approximately one-third of the
      state's adults are affected by pain on at least a monthly basis. Most of this
      pain is moderate to severe and quite frequent--occurring daily for the majority
      of pain sufferers. The study also illuminates social and cultural dimensions of
      pain, revealing that a) the presence of pain negatively affects almost every
      facet of life, from sleep and work to relationships, leisure activities, and
      mental health, and b) respondents attitudes and beliefs are often at variance
      with modern approaches to pain management. Knowledge gained could have critical
      implications for understanding patients and the treatment of pain.

PMID- 16295299
TI  - Twenty-four hours.

PMID- 16295300
TI  - Governor Hugh White's address at UMC dedication in 1955.

PMID- 16295301
TI  - The value of "quality" in the care we give.

PMID- 16295302
TI  - Critical thinking: How do we know it in nursing education and practice?

PMID- 16295303
TI  - Faculty matters. Susan Pierce.

PMID- 16295304
TI  - Assumptions and realities of the NCLEX-RN.
AB  - Every three years the National Council of State Boards of Nursing conducts a
      practice analysis to verify the activities that are tested on the licensure exam
      (NCLEX-RN). Faculty can benefit from information in the practice analysis to
      ensure that courses and experiences adequately prepare graduates for the NCLEX
      RN. This summary of the practice analysis challenges common assumptions and
      provides recommendations for faculty.

PMID- 16295305
TI  - Critical thinking in nursing education and practice as defined in the literature.
AB  - Critical thinking is frequently discussed in nursing education and nursing
      practice literature. This article presents an analysis of the concept of critical
      thinking as it applies to nursing, differentiating its use in education and
      practice literature. Three computerized databases (CINAHL, MEDLINE, and EBSCO)
      were searched for the years 1981 to 2002, using the keywords critical thinking.
      References were stratified into two 11-year periods (1981-1991, 1992-2002) to
      identify changes in the concept over time and integration of the concept
      differentially into nursing education and nursing practice. A random sample of
      literature from each stratum was coded for definitions, attributes, surrogate
      terms, referents, antecedents, and consequences of critical thinking. Critical
      thinking as a nursing concept has matured since its first appearance in the
      literature. It is well defined and has clear characteristics. However,
      antecedents and consequences are not well defined, and many consequences are
      identical to attributes and surrogate terms. Additional work is needed to clarify
      the boundaries of the concept of critical thinking in nursing.

PMID- 16295306
TI  - A crisis in critical thinking.
AB  - Aggregate results for competency assessment of new registered nurses using the
      Performance Based Development System indicate that most new graduates do not meet
      expectations for entry-level clinical judgment ability.This article discusses
      implications for nursing education and offers recommendations for developing
      clinical judgment in nursing students.

PMID- 16295307
TI  - Community-based nursing education of prelicensure students: settings and
      supervision.
AB  - This study of prelicensure nursing programs had a fourfold purpose: 1) describe
      what community-based settings are being used by faculties in associate degree
      (AD) and baccalaureate degree (BSN) programs to provide community-based nursing
      care experiences; 2) explore whether or not the settings used in AD and BSN
      programs differ; 3) describe how faculties in AD and BSN programs provide for
      supervision of students in community-based settings; and 4) synthesize from the
      data what might be best practices for faculty-student supervision in community
      based settings. A web-based survey was sent to 827 accredited AD and BSN programs
      with usable email addresses; 324 programs (39 percent) completed and returned the
      surveys. Findings indicated that students were placed in a variety of settings,
      including public health departments, schools (K-12), prisons, and home care.
      Community-based activities were in the following categories: immunizations,
      surveillance, data collection, health teaching, case management, treatments, and
      procedures. Depending on the activity, students performed nursing functions
      independently 4 percent to 39 percent of the time. Depending on the activity,
      preceptors were sole supervisors 27 percent to 40 percent of the time.
      Telephones, cell phones, and pagers were the primary means of faculty-student
      contact. AD and BSN students in the same settings performed the same activities.
      The only significant differences were that BSN students were placed in K-12
      schools for community-based experiences more often than AD students, and they
      engaged in case management more often than AD students. Based on these findings,
      a model for community-based education is proposed.

PMID- 16295308
TI  - Impact of a service-learning project on nursing students.
AB  - This article describes the incorporation of a service-learning project in a
      maternal-infant health course in a baccalaureate nursing program. Partnership
      goals between university faculty and project Early Head Start were to develop and
      implement a clinical education experience that not only enhanced services to
      teenage mothers, but also taught students key elements in the delivery of
      community services to this vulnerable population. This article examines the
      impact of the service-learning experience on students' understanding of
      diversity, perceptions of social responsibility in community service, and health
      care issues. Implications for faculty investment of time and resources are also
      explored.

PMID- 16295309
TI  - The second-degree accelerated program as an innovative educational strategy: new
      century, new chapter, new challenge.
AB  - This article discusses one institution's experience with a one-year, accelerated
      second-degree program and the role such programs play as part of a solution to
      the current nursing shortage.

PMID- 16295310
TI  - Bonding of nursing practice and education through research. 1984.

PMID- 16295312
TI  - Constituent leagues: professional investments that make a difference.

PMID- 16295311
TI  - Preparing for evidence-based practice: revisiting information literacy.

PMID- 16295313
TI  - Social security: a program and policy history.
AB  - Many of the federal and state programs that provide income security to U.S.
      families have their roots in the Social Security Act (the Act) of 1935. This Act
      provided for unemployment insurance, old-age insurance, and means-tested welfare
      programs. The Great Depression was clearly a catalyst for the Social Security Act
      of 1935, and some of its provisions--notably the means-tested programs--were
      intended to offer immediate relief to families. However, the old-age insurance
      program-the precursor to today's Old-Age, Survivors, and Disability Insurance, or
      Social Security, program-was not designed specifically to deal with the economic
      crisis of that era. Indeed, monthly benefit payments, under the original Act,
      were not scheduled to begin until 1942. In addition, from the beginning, the
      Social Security program has embodied social insurance principles that were widely
      discussed even before the onset of the Great Depression. The first four decades
      of the Social Security program were, in general, ones of expansion. In fact, the
      program was expanded even before it became truly operational. In 1939, amendments
      added child, spouse, and survivor benefits to the retirement benefits authorized
      by the 1935 Act. Those amendments also allowed for monthly benefits to begin in
      1940. Although the program was not changed substantially during the war years and
      the initial postwar period, the 1950s were a transformational decade in the
      program's history: benefit amounts were increased substantially, coverage under
      the program became close to universal, and a new disability insurance benefit was
      offered. The 1960s witnessed additional growth in Social Security, but the most
      important development in social insurance occurred in health insurance, with the
      creation of the Medicare program in 1965. Legislative actions in the 1970s had
      profound effects on the Social Security program and, indeed, set the stage for
      many of today's reform debates. Large benefit increases, a new benefit formula
      that was erroneously generous, and other changes in the early 1970s created a
      situation in which annual program costs, as a share of gross domestic product,
      increased during a 12-year period from about 3 percent to 5 percent. In 1977,
      amendments to the Act corrected the flawed benefit formula and made other changes
      in the financing of the system to shore up the program. Thus, the 1970s represent
      a watershed in the program's history-program growth gave way to increasing
      concerns about the program's finances. Those concerns were reflected in the
      amendments to the Act in 1983, which were the last major changes to the program.
      These amendments, based largely on recommendations from a commission chaired by
      Alan Greenspan, adjusted benefits and taxes to address pressing near-term
      financing problems faced by the system. Although the Greenspan Commission focused
      to a large extent on short-range issues, the resulting reforms have generated
      large surpluses in the program and the buildup of a substantial trust fund.
      However, the looming retirement of the baby boomers and several other demographic
      factors will, according to projections, result in the exhaustion of the trust
      fund by 2042.

PMID- 16295315
TI  - Individual Accounts in other countries.

PMID- 16295314
TI  - Literature review of long-term mortality projections.

PMID- 16295316
TI  - Lifetime earnings, social security benefits, and the adequacy of retirement
      wealth accumulation.

PMID- 16295317
TI  - Medicare gaps and widow poverty.

PMID- 16295318
TI  - Ethanol-induced dysfunction of hepatocytes and leukocytes in patients without
      liver failure.
AB  - The repeated intake of a great amount of ethanol is followed by functional and
      organic changes in the body. The intestinal absorption of alcohol is accompanied
      by an increased absorption of Gram negative bacteria endotoxins in the portal
      blood. In the liver, endotoxins stimulate CD14 receptors on the membrane of
      Kupffer cells, with a secondary inflammatory liver response, consisting in the
      secretion of proinflammatory cytokines and acute phase proteins. Simultaneously,
      alcohol metabolism in the hepatocytes by alcohol dehydrogenase, microsomal
      enzymes and catalase pathways determines a large production of ROS (reactive
      oxygen species), with secondary oxidative aggression on all liver cells:
      hepatocytes, Kupffer cells, endothelial sinusoidal cells, hepatic stellate cells
      and liver s lymphocytes. The oxidative aggression, as well as the intermediary
      products of the alcohol metabolism, cause a structural change of the antigenic
      structures of the liver and of the released proteins, that induces an immune
      response on the both pathways (humoral and cellular). The pathophysiological
      mechanisms and the paraclinical characteristics of the ethanol-induced liver
      failure are well known, so we were interested to study the patients with chronic
      alcoholism, but no clinical or paraclinical sign of liver failure, in order to
      describe the liver's protective mechanisms. For this reason, 153 patients with
      chronic alcoholism were divided into four test lots, in order to determine: the
      activity and the serum level of ceruloplasmin, plasma level of MDA
      (malondialdehyde), lactic and pyruvic acids, serum level of transferrin, alpha1
      antitrypsin, CRP (C reactive protein), C3 fraction of the complement, IgA, IgG,
      IgM, IL-1beta, IL-6 and IL-8, cytosolic level of the cytochrome c in the
      circulating leukocytes. An immunophenotype study (as normal markers) on the
      peripheral blood lymphocytes was performed, too. The results demonstrate an
      important oxidative aggression induced by three sources: the alcohol metabolism
      in the hepatocytes, activated Kupffer cells and activated neutrophils that have
      infiltrated the liver, due to the chemoattractant effect of IL-8. This aggression
      induces apoptosis and necrosis of the liver cells. The major liver protective
      factor is, in our opinion, IL-6, due to its important antioxidant, antiapoptotic
      and proregenerative demonstrated actions. This protective effect of IL-6 is
      accompanied by antioxidant and antiprotease actions of ceruloplasmin, alpha1
      antitrypsin and transferrin. We consider that an increased serum level of IL-6
      accompanied by a decreased level of IL-1beta signify that antiapoptotic,
      antioxidant and proregenerative liver mechanisms prevail against proapoptotic and
      necrotic mechanisms. On the other hand, the ethanol-induced apoptosis of
      leukocytes (especially of the B cells) is very important, probably due to the
      absence of IL-6 protective action on these cells. The apoptosis of the
      circulating leukocytes is proved by their significant increase of the cytochrome
      c cytosolic level. The ethanol-induced liver immune response is predominantly
      cellular, as proved by the decreased ratio T helper (CD4+)/T cytotoxic (CD8+) in
      the peripheral blood. It is very important to observe that these significant
      immunologic changes appear before clinical or paraclinical signs of hepatic
      failure start. All these parameters were investigated in three groups of
      patients: chronic alcoholics, chronic alcoholics in the first 24 hours of the
      withdrawal and chronic alcoholics with acute alcohol intoxication, so the
      aggression types and the protective mechanisms were measured and differentiated
      in each "ethanolic status".

PMID- 16295319
TI  - Phenotypical changes during in vitro cultivation of monocytes derived immature
      dendritic cells.
AB  - Dendritic cells (DC) form a link between the first line of host defence and
      cellular immunity. In the present study we investigated the effect of cultivation
      time in generation of immature dendritic cells (iDCs) in vitro from human
      peripheral blood (PB) monocytes and the influence of iDCs on the oxygen free
      radicals (OFR) release by polymorphonuclear granulocytes (PMN) stimulated with
      opsonized zymozan (OZ) and concanavalin A (ConA). Our data suggest that the
      differentiation in vitro of PB monocytes in iDCs is influenced by the health
      status of the cell donor, and more by the concentration of cytokines GM-CSF and
      IL-4 in the system than by the time of cultivation. The in vitro experiments
      performed demonstrated the interactions between iDC and PMN granulocytes,
      evaluated by enhanced release of OFR.

PMID- 16295320
TI  - Experimental studies on bacterial product cantastim derived from Pseudomonas
      aeruginosa. VI. Protection in tolerant mice.
AB  - Endotoxin tolerance is defined as a hyporesponsiveness state to a second
      stimulation with lipopolysaccharide (LPS). This refractory state is primarily
      associated with an attenuated cytokine production. Whether this down-regulation
      of cytokine production results in an increased susceptibility to infection
      remains a matter of controversy. The aim of this study was to investigate the
      resistance of tolerant mice to a subsequent bacterial infection and the role of
      bacterial immunomodulator CANTASTIM (CS) in this experimental model. We have
      shown that the LPS-tolerant mice (intraperitoneally inoculated with LPS
      Salmonella typhimurium 10 microg/mouse, daily for two days) were protected
      against a challenge with Pseudomonas aeruginosa (LD 100) administered 24 h later.
      On the contrary, when the animals were challenged 1 h after the last LPS
      injection, they did not survive. However if these animals were pre-treated with
      CS 3 days before LPS treatment, they became resistant to a subsequent bacterial
      challenge. More interestingly, if the treatment with LPS was substituted with CS
      (same schedule, route of administration and doses) there was a significant
      increase in the survival of mice challenged with Pseudomonas aeruginosa after
      either 1 h or 24 h. In this case, the increase in the rate of survival was
      correlated with an enhanced production of IL-10 in the peritoneal cavities of CS
      treated mice as compared to LPS treated mice.

PMID- 16295322
TI  - The physician and family planning.

PMID- 16295321
TI  - Comparative study of different methods for detection of toxic and other enzymatic
      factors in Vibrio cholerae strains.
AB  - The purpose of this work was to characterize the toxin profile and the presence
      of other virulence factors involved in the pathogenesis and biology of 13 V.
      cholerae O1 (11 clinical cases and 2 waters) and 6 V. cholerae non O1 strains (4
      clinical cases and 2 waters) using genetic (PCR), immunological (RPLA),
      biochemical (NAD degradation, haemolysis, Kanagawa phenomenon, caseinase,
      lecithinase, mucinase, amylase, esculine hydrolysis) and cell culture (Vero E6,
      HEp-2) assays. The results indicated a concordance between PCR-RPLA (84%), PCR
      NAD (73%) and RPLA-NAD (84%) methods. The sensitivity of RPLA and NAD degradation
      methods were comparable to PCR in detecting CT in Vibrio cholerae O1 strains.
      Although NAD degradation method was not exclusively specific for the CT
      detection, it proved its usefulness in screening certain virulent, CT-negative
      clones of V. cholerae. The cytotoxic effect on Vero E6 cells, enzyme production
      (Kanagawa haemolysins, lecithinase, caseinase, esculine hydrolysis) as well as
      adherence ability on inert substrate proved to be much more constant in V.
      cholerae non O1 (CT- negative) than in V. cholerae O1 (CT-positive). All V.
      cholerae non O1 strains isolated in diarrheal cases were Kanagawa positive. This
      complex of virulence factors detected in V. cholerae non O1 strains could
      probably contribute during interepidemic periods to human-to-human transmission
      and to greater resistance as compared to O1 strains in the environment.

PMID- 16295323
TI  - [Benign chondroblastoma. A case report and review of the literature].

PMID- 16295324
TI  - The immune system development and function.
AB  - The immune system in its four components T cells, B cells, complement and
      phagocytes is vital for the defense of the organism against foreign substances or
      antigens. Elimination of an antigen involves the interaction of the four
      complements of the immune system with antigen and with each other. The final
      common pathway is the breakdown of the antigen by the intracellular machinery of
      the phagocytic cell. The maintenance of the self depends on the integrity of the
      immune system. Whenever this integrity is breached (by aging, congenital immune
      deficiency, cytotoxic drugs, irradiation, infiltrative disease...) the organism
      becomes prone to uncontrolled invasion by antigens (viruses, bacteria, fungi,
      neoplasms) and its survival is threatened.

PMID- 16295325
TI  - Prevention of infertility.

PMID- 16295326
TI  - Protein losing gastroenteropathy in constrictive pericarditis.
AB  - A case of constrictive pericarditis with PLGE is reported. It is the nineteenth
      case in the world literature. The fatal outcome is contributed to late diagnosis
      and refusal of surgery. It is possible that nine out of sixty eight cases of
      constrictive pericarditis have suffered from the same condition in a five year
      period in the same hospital. Early diagnosis is rewarding and could be achieved
      by a high index of suspicion and an outlook for the diagnostic markers.

PMID- 16295327
TI  - Serum immunoglobulin levels in normal children and adults in the Lebanese and
      other Arab Middle Eastern populations.
AB  - Serum immunoglobulin levels were determined in 1000 serum samples of normal
      middle easterners. Ig levels in mothers at delivery were normal except for a
      depressed IgG level. In cord blood the level of IgG was higher than its level in
      mothers, but no IgA or IgD was found. IgD was formed in some instances in the
      sera of infants in the first week of life. IgG showed a pattern similar to that
      described by others with the lowest values at 1-2 months, increasing gradually so
      that by 1-3 years the normal adult blood level is reached. IgA levels continued
      to increase with age and although no definite explanation is available, it is
      interesting to speculate on the possible relationship to the increased incidence
      of intestinal parasitism. IgM showed significant differences between males and
      females being higher in the latter. IgD levels reached maximum levels by 3-5
      years, and mean levels ere lower after the 14th year.

PMID- 16295328
TI  - Acute myocardial infarction in the young.
AB  - In space of 2 years our CCU admitted 38 patients under 40 years and the trend
      seems to be on the increase. The high prevalence of risk factors, the low
      frequency of arrhythmias and the low mortality rate were notable features. The
      role of psychological and physical stress in the pathogenesis of cor H. D.
      deserve more attention. The fact remains that the only road to a substantial
      reduction in premature death from CHD must be in its prevention.

PMID- 16295329
TI  - The immune system: primary immune deficiency diseases.
AB  - Table 1 summarizes the major IDD and the methods used for their diagnosis and
      treatment. The clue to the diagnosis of IDD remains a high index of suspicion
      when one encounters a child or an adult with recurrent infections. IDD must be
      relatively common in Lebanon because of the high rate of interfamily marriages.
      With a heightened awareness and few easily available laboratory methods
      (underlined in table 1) the primary physician should be able to make the
      diagnosis of most of these diseases.

PMID- 16295331
TI  - Gonorrhea in the male: some aspects of treatment in Lebanon.
AB  - One hundred male patients with acute gonococcal urethritis were treated with
      various antibiotic and chemotherapeutic regimens. Pivampicillin, 1400 mg orally
      in two divided does at 5 hours' interval gave 100% cure in 60 patients.
      Gentamicin, 280 mg IM in one dose was equally efficaceous in 15 patients.
      Ampicillin and Trimethoprim-sulfamethoxazole gave cure rates of around 70%. While
      the results of the first two groups were in agreement with data published in
      different parts of the world, our results with the later two groups were contrary
      to those of other authors. The need for periodic evaluation of various antibiotic
      regimens in the treatment of gonorrhea is indicated.

PMID- 16295330
TI  - Renal lithiasis in Lebanon: I--the chemical types of urinary calculi.
AB  - The results of chemical analyses of 429 urinary calculi are presented and
      classified according to chemical composition. Some of the general features of the
      different chemical types of the stones are discussed. Although the general
      distribution of the chemical types of stones in Lebanon is essentially similar to
      that reported from other countries, the two striking features of this series are:
      (1) a relatively lower incidence of infection stones (i.e. stones containing
      magnesium ammonium phosphate) and (2) a relatively higher incidence of stones
      containing a mixture of uric acid and calcium oxalate and/or calcium phosphate.

PMID- 16295332
TI  - [Schwannoma of the small bowel. Report of a case with a suggestive radiologic
      pattern].

PMID- 16295333
TI  - Smoking and chest diseases.

PMID- 16295334
TI  - Splenectomy in a "resistant" case of kala-azar.

PMID- 16295335
TI  - A 17-year old girl was admitted to AUH because of hematemesis, melena and
      jaundice.

PMID- 16295336
TI  - In memoriam: Dr. Hrant Toros Chaglassian (1905-1965).

PMID- 16295337
TI  - Exploring the impact of instructional approaches on the learning and transfer of
      medication dosage calculation competency.
AB  - AIM: The ability of nurses to perform accurate drug dosage calculations has
      repercussions for patients' well-being. How best to assist nurses develop
      competency in this area is paramount. This paper presents findings of a study
      conducted with undergraduate nurses to determine the effect of three
      instructional approaches on the learning of this skill. METHOD: The quasi
      experimental study exposed participants to one of three instructional approaches:
      integrative learning, computerised learning and a combination of integrative and
      computerised learning. Quantitative and qualitative approaches were used to
      explore differences in the instructional approaches and gain further
      understanding of the learning process. RESULTS: There was no statistical
      difference between the three instructional approaches on knowledge acquisition
      and transfer measures, other than measures for procedural knowledge, which was
      significant (F(2,47) = 3.33 at p < .044). A least-significant difference post hoc
      test (alpha = 0. 10) indicated computerised learning was significantly more
      effective in developing procedural knowledge. CONCLUSION: The provision of
      instructional strategies, which facilitate development of conditional knowledge
      and automaticity, is necessary for competency development in dosage calculations.
      Furthermore, the curriculum must incorporate authentic tasks and permit time to
      support competency attainment.

PMID- 16295338
TI  - Self-directed learning and portfolio development for nurses: developing workbooks
      as a facilitative tool.
AB  - Workbooks are often used for discipline-specific learning in academic
      institutions but there is growing recognition of their potential usefulness in
      the clinical setting to promote learning and professional development. The
      purpose of this paper is to share some tips/guidelines for those clinical staff
      interested in developing self-directed learning programs using a workbook
      approach. Combined with skilled facilitation, custom designed workbooks based on
      adult learning theories can enhance skills and encourage portfolio development in
      the clinical setting. This cost and time effective approach utilises existing
      resources to cater to diverse needs and topics, building sustainable
      collaborations. This paper will argue that the proposed program has the potential
      to contribute to healthcare improvement by promoting skill development amongst
      staff and contributing to evidence-based practice.

PMID- 16295339
TI  - Welcome to the techno highway: development of a health assessment CD-ROM and
      website.
AB  - Traditionally teaching nursing students psychomotor skills took place in a
      laboratory setting; however, recent developments in computer technology have
      revolutionised how educators can transfer knowledge. To meet the need for an
      efficient and interactive learning experience a software product was required to
      educate nursing students about health assessment techniques. This paper presents
      how existing 'old technology' of a video was given new life by embracing new
      technology, resulting in development of an interactive CD-ROM with supporting
      WebCT. This innovation reflects a more flexible approach to learning as it is
      dynamic, portable, self-paced and more convenient for adult learners especially
      those in remote areas.

PMID- 16295340
TI  - Interprofessional practice: learning how to collaborate.
AB  - Interprofessional practice is a way of practicing that is based on collaboration.
      We cannot assume that health professionals have either the skills or attributes
      required for interprofessional practice. They may need to learn how to
      collaborate. Developing interprofessional practice requires a commitment to
      engage in shared learning and dialogue. Dialogue has the potential to encourage
      collegial learning, change thinking, support new working relationships, and
      improve client care.

PMID- 16295341
TI  - Magnet hospital research pilot project conducted in hospitals in Western
      Australia.
AB  - The factors causing nurses to leave nursing are well known and published. The
      main aim of the research pilot project was to explore and describe the reasons
      that attract nurses to a specific hospital and that motive them to remain working
      at that hospital. Data were collected through surveys of different categories of
      nurses working in selected 'Magnet Hospitals' in Perth (Western Australia).
      Biographical data were analysed through quantitative methods and content analysis
      was employed to analyze qualitative data. Motivational findings indicate specific
      organizational factors (such as staff development programs) and significant
      personal circumstances.

PMID- 16295342
TI  - Power and empowerment: critical concepts in the nurse-client relationship.
AB  - Two key concepts in health promotion within the nurse-client relationship are
      power and empowerment. Theorists and researchers have not achieved consensus on
      how they are to be defined and addressed. However, both power and empowerment are
      recognized to occur at macro and micro levels, and as such need to be addressed
      at each level. Using a critical nursing perspective, this article explores these
      concepts it identifies concerns that arise around power and risks that arise in
      empowerment practice. Nurses are challenge to develop a new way of seeing
      empowerment practice, and encouraged to focus on 'being with' clients, rather
      than 'doing to' them.

PMID- 16295343
TI  - New graduate identity: discursive mismatch.
AB  - For many new graduates the transition from nursing student to a professional in
      practice is marked by conflict and tension. Given that conflict may ensue from
      differing discursive constructions of new graduates, this article reports a
      review of discursive construction between new graduates from two institutions
      with vested interests in nursing graduates--comparing health service
      organisations and educational institutions in Victoria. Four discourses, common
      to both sets of texts and constitutive of new graduate identity were identified:
      these were the discourse of nursing practice; the discourse of the good nurse;
      the discourse of knowing and thinking; and the discourse of statute and
      regulation. A discourse peculiar to health service organisations only was
      identified as an organisational and bureaucratic discourse. This review reports
      the new graduate, as constructed in education texts, as a rational, independent,
      critically thinking and knowing care giver. In contrast, in health service
      organisation texts, the new graduate is constructed as a functional, efficient,
      organisational operative, providing a nursing service. New graduates are
      concluded to experience multiple discursive dissonances in their first employment
      which stem from differing constructions of new graduate identity within
      institutional discourses. If tensions experienced in the transition as
      discursively generated are understood, previously unthought of ways preparing and
      introducing nurses to the work place may ensue.

PMID- 16295344
TI  - Nurses' experiences of caring for culturally diverse patients in an acute care
      setting.
AB  - Identification of nurses' experiences of caring for culturally diverse patients
      in acute care settings contributes to transcultural nursing knowledge. This
      qualitative study aims to describe nurses' experiences of caring for culturally
      diverse adult patients on medical and surgical wards in an acute care setting.
      These experiences identify current practice and associated issues for nurses
      caring for culturally diverse clients. A purposive sample of ten registered
      nurses was interviewed and transcripts analysed. Main findings were acquiring
      cultural knowledge, committing to and engaging with culturally diverse patients.
      Strategies for change developed from these findings focus on increasing cultural
      competency of nurses by: implementing a formal education program; developing
      partnerships with patients and their families to increase cultural comfort; and
      increasing organisational accommodation of the culturally diverse with policy
      review and extension of resources. Further research to explore issues for
      bilingual nurses and to describe the experiences of culturally diverse patients
      and their families in general acute care settings is recommended.

PMID- 16295345
TI  - Transforming possibilities of care: Goan migrant motherhood in New Zealand.
AB  - Little is known about the maternity experiences of migrant mothers in
      Aotearoa/New Zealand--and in particular the ways in which women adapt and survive
      when separated from traditional postnatal practices and family support. This
      paper reports on a study of the maternity care experiences of women from Goa
      (India) in Auckland, New Zealand. Multiple research strategies were incorporated
      into the process to prevent reproduction of deficiency discourses. Interviews
      were carried out with Goan women who had experiences of migration and motherhood.
      The findings revealed that as a consequence of motherhood and migration, migrant
      mothers were able to reclaim and re-invent innovative solutions. Nurses and other
      health professionals can have a significant role in supporting women and their
      families undergoing the transition to parenthood in a new country and develop
      their knowledge and understanding of this dual transition.

PMID- 16295347
TI  - After Katrina: 'doing whatever it takes'.

PMID- 16295348
TI  - Special election: just say No!

PMID- 16295346
TI  - Developing interpersonal relationships with adolescents with anorexia nervosa.
AB  - Anorexia nervosa is a complex eating disorder that usually develops during
      adolescence. This paper reports how paediatric nurses develop professional
      interpersonal relationships with adolescent patients with anorexia nervosa. The
      study used a grounded theory approach to data collection and analysis. Data were
      collected using in-depth interviews from ten registered nurses who worked on a
      paediatric ward. The findings revealed two foci of care: 'interacting with
      nurses', and 'interacting with patients', with interrelated categories and
      strategies. A core category highlighted the importance of instigating an
      individual focus when developing professional interpersonal relationships with
      patients with anorexia. Contextual factors emphasise the broader influences that
      modified the way nurses developed relationships with these patients. The findings
      have implications for clinical practice, education, unit administration, and
      further research, and these are examined. Nurses who use this approach are better
      positioned to gain understanding of individuals experiencing the disorder and to
      develop professional interpersonal relationships.

PMID- 16295349
TI  - Stars come out to spotlight CNA role in Arnold fight.

PMID- 16295350
TI  - Global warning.

PMID- 16295351
TI  - Behind the redwood curtain.

PMID- 16295361
TI  - Commentary on the CNA code of ethics.

PMID- 16295362
TI  - The legal status of the fetus.

PMID- 16295363
TI  - Participatory approaches in the co-design of a comprehensive referral system.
AB  - Reducing mortality rates for women and children in Third World countries requires
      improved access to quality, affordable health services. In this article, the
      authors describe the experiences of the University of Ottawa School of Nursing
      and its Chinese partner, the Yunnan Provincial Public Health Bureau, in
      developing and implementing a comprehensive referral system for impoverished
      rural women and children as part of the Yunnan Maternal and Child Health Project,
      a six-year dollar 6-million bilateral initiative implemented across 10 counties
      (population 2.2 million) in Yunnan province, China. Through engaging government
      officials, health workers, local leaders and village women in dialogue and
      reflection, Canadian and Chinese partners developed a common understanding about
      underlying determinants affecting maternal and child health services; explored
      appropriate intervention options; and developed an innovative comprehensive
      referral system.

PMID- 16295364
TI  - Best practices in stroke care.
AB  - In 2001, the Ontario Ministry of Health and Long-Term Care introduced the Ontario
      Stroke Strategy by designating regional stroke centres across the province. The
      primary role of these centres is to coordinate stroke care within the region and
      across the care continuum in keeping with best practices. Concurrently, Trillium
      Health Centre was identifying best practice projects to support its ongoing quest
      for excellence. With Trillium designated as a regional stroke centre, acute
      ischemic stroke care was an obvious choice for a best practice project. The aim
      of the project was to improve access to care and quality of care for stroke
      patients from emergency through acute care to in-patient rehabilitation. The team
      chose the rapid cycle change methodology. This approach to quality improvement
      advocates the testing of a series of small changes (i.e., process improvement
      ideas) in tandem with measurements to assess the impact of the change to drive
      further process improvements. The project was deemed a success, resulting in
      significant improvements in the timeliness and quality of care.

PMID- 16295365
TI  - Building and sustaining a career culture.

PMID- 16295366
TI  - Nursing excellence by design. Interview by Barbara Sibbald.

PMID- 16295367
TI  - Current perspectives of herpesviral retinitis and choroiditis.
AB  - Vision-threatening viral retinitis are primarily caused by members of the
      herpesvirus family. The biology and molecular characterization of herpesviruses,
      clinical presentations of retinopathies, pathology and pathogenesis including the
      host responses, epidemiology and the laboratory methods of aetiological diagnosis
      of these diseases are described. Clinical syndromes are acute retinal necrosis
      (ARN), progressive outer retinal necrosis (PORN), cytomegalovirus (CMV)
      retinitis, multifocal choroiditis and serpiginous choroiditis besides other viral
      retinopathies. Herpes simplex virus (HSV) retinitis is more common in
      immunocompetent persons while varicella zoster virus (VZV) affects both
      immunocompetent and immunosuppressed patients equally. CMV retinitis is most
      common among patients with AIDS. The currently employed laboratory methods of
      antigen detection, virus isolation and antibody detection by enzyme linked immuno
      sorbent assay (ELISA) have low sensitivity. Polymerase chain reaction (PCR) has
      increased the value of diagnosis due to its high clinical sensitivity and
      absolute specificity in detection of herpesviruses in intraocular specimens.

PMID- 16295368
TI  - Nucleolar organizer regions (NORs) in simple and proliferating trichilemmal cysts
      (pilar cysts and pilar tumors).
AB  - Simple trichilemmal cysts or pilar cysts and pilar tumors are relatively rare
      entities often under-reported by pathologists. The pilar cysts are thought to
      proliferate and progress to pilar tumors. These pilar tumors can further undergo
      malignant change. We analyzed 25 pilar cysts and eight pilar tumors, including
      three with atypia and one malignant pilar tumor, with a view to study the above
      progression and assess the degree of cell proliferation using the Nucleolar
      Organizer Regions (AgNORs). There was a progressive increase in the AgNOR count
      from one dot per nucleus in pilar cysts to 1.5-2 in benign pilar tumors. AgNORs
      in pilar tumors with atypia (2.8) was more than the benign pilar tumors but were
      definitely less than the malignant pilar tumors (3.5). The malignant pilar tumor
      showed bizarre AgNORs and cells with as many as eight to nine AgNORs. Thus AgNOR
      counts suggested that there is a progressive increase in the degree of cell
      proliferation and thereby the AgNOR staining from pilar cysts to pilar tumors.
      This AgNOR staining could also be used to assess the cell proliferation in case
      of pilar tumors with atypia where it is difficult to rule out malignancy.

PMID- 16295369
TI  - Pneumocystis carinii pneumonia after renal transplantation.
AB  - Being immuno-suppressed, renal allograft recipients are at increased risk of
      contracting various infectious complications. Pneumocystis carinii pneumonia
      (PCP) is one of the important opportunistic infection causing high morbidity and
      mortality in these patients. Majority of studies has reported the occurrence of
      PCP during 6 months to one year after renal transplantation. This communication
      describes occurrence of PCP in five renal allograft recipients 10 weeks to 72
      months after transplantation. In view of elusive presentation, strong clinical
      and radiological suspicion followed by direct demonstration of the organisms is
      essential for early diagnosis and prompt treatment. These observations also
      indicate that PCP is an emerging opportunistic infection in immuno-compromised
      patients in tropical countries.

PMID- 16295371
TI  - Static telepathology consultation service between Tata Memorial Centre, Mumbai
      and Nargis Dutt Memorial Charitable Hospital, Barshi, Solapur, Maharashtra: an
      analysis of the first 100 cases.
AB  - Telepathology is the practice of pathology at a distance. Static telepathology is
      employed to achieve teleconsultation between a tertiary cancer referral centre,
      Tata Memorial Centre and a sister concern in rural area viz. Nargis Dutt Memorial
      Cancer Hospital, Barshi, Solapur. This is an analysis of the first 102 cases. Two
      transcontinental consultations have not been included in statistical analysis. A
      diagnosis was offered in 99 (99%) cases; whereas it was deferred in only I (1%)
      case. Clinically important or relevant diagnosis were achieved in 93/ 99 (93.93%)
      of cases. Major discrepancies were encountered in 6/99 (6.06%) of cases. A total
      of 79% of cases were reported within 3 days, of which 32% were reported within 8
      hours (a single working day) and 47% within 1-3 days. Telemedicine can be used
      effectively to bridge the gap between medically underprivileged, geographically
      distant rural areas and advanced centers with technical expertise using cheaper
      static store and forward methodology.

PMID- 16295370
TI  - Infectious markers in blood donors of East Delhi: prevalence and trends.
AB  - All blood donors Voluntary and Replacement who have donated blood in the centre
      or in the voluntary blood donation camps, were analyzed for the prevalence of
      infectious markers over a period of 3 years from 1997 to 1999. A total of 52500
      blood units were collected and screened for hepatitis B surface antigen (HBsAg),
      antibodies to HIV I and II and VDRL reactivity. Seropositivity was 471 (0.8%) for
      HIV I and II, 963 (1.8%) for HbsAg, 1449 (2.76%) for VDRL and 64 (0.5%) for anti
      HCV. Voluntary donors were comparatively safe. The seropositivity for HIV showed
      increasing trend between 1997 to 1999.

PMID- 16295372
TI  - Study of semen analysis and testicular biopsy in infertile male.
AB  - A study of semen analysis and testicular biopsy was done in 50 infertile males.
      Semen analysis and testicular biopsy form important screening tools. Commonest
      age group affected was 21-40 years with sterility of 2-6 years duration. Smoking
      or tobacco chewing for longer periods may change semen quality. On semen
      analysis, 52 percent cases had azoospermia, 46 percent cases had oligospermia and
      02 percent cases had normal count. Among oligospermics and normospermics,
      majority had more than 50 percent motility. Conditions like varicocele,
      undescended testis, inflammation can lead to hypospermatogenesis; the lesion is
      most common with 26 percent incidence. Though the specific reason of sertoli cell
      only is not known, it is also common with 26 percent incidence. Second most
      common finding was atrophy with 18 percent incidence, which may be acquired due
      to history of trauma, exposure to high temperature, habits of tobacco chewing
      and/or smoking or inflammatory conditions.

PMID- 16295373
TI  - Mesenchymal chondrosarcoma: a series of 23 cases.
AB  - A total of 23 cases of mesenchymal chondrosarcoma were studied from the
      histopathology records spanning 23 years. There were 16 men and 7 women afflicted
      with this tumor and their mean age was 28.1 years. The radiological features,
      histology and treatment outcomes have been studied. Osseous and extra-osseous
      mesenchymal chondrosarcomas are compared and the differential diagnosis
      discussed.

PMID- 16295374
TI  - Primary pulmonary choriocarcinoma--a series of 7 cases.
AB  - Primary pulmonary choriocarcinoma is a rare manifestation of extra-genital
      malignant germ cell tumour. This is a report of seven such cases, seen in autopsy
      and surgical materials in a span of 20 years. The age range was from 25 to 60
      years, affecting six women and one male. These are aggressive tumours requiring
      prompt therapy. Only one among the seven survived.

PMID- 16295375
TI  - Serial scrape smear cytology of radiation response in normal and malignant cells
      of oral cavity.
AB  - Serial scrape smears were taken from 111 patients receiving radiotherapy for
      squamous cell carcinoma of the oral cavity. The surface of the tumour and the
      normal mucosa on the opposite side was scraped before and after delivery of
      various fractions of radiotherapy and were evaluated by light microscopy. The
      number of cells exhibiting changes like multinucleation, micronucleation, nuclear
      budding, binucleation and cytoplasmic granulation were counted. The results were
      expressed as abnormality per 1000 cells. Each parameter showed a statistically
      significant increase with radiation dose in both normal and malignant oral cells.
      In the normal mucosal cells the mean values after 6Gy and 24Gy respectively were
      0.83 and 2.91 (p<0.001) for cells with multinucleation, 1.83 and 4.42 (p<0.001)
      for micronucleation, 2.58 and 5.15 (p<0.001) for nuclear budding, 5.92 and 12.58
      (p<0.001) for binucleation, and 3.67 and 7.17 (p<0.001) for cytoplasmic
      granulation. On the other hand, in malignant cells, the mean values before and
      after treatment with 24 Gy respectively, were 3.14 and 7.08 (p<0.001) for cells
      with multinucleation, 1.05 and 5.97 (p<0.001) for micronucleation, 2.54 and 8.82
      (p<0.001) for nuclear budding 7.11 and 27.93 (p<0.001) for binucleation and 5.32
      and 12.02 (p<0.001) for cytoplasmic granulation. The study showed that there is a
      dose-related increase in multinucleation, micronucleation, nuclear budding,
      binucleation and cytoplasmic granulation after various fractions of radiotherapy
      in both normal and malignant oral cells, however these changes are more marked in
      the malignant cells.

PMID- 16295376
TI  - Value of nucleated red blood cells in predicting severity and outcome of
      perinatal asphyxia.
AB  - The objective of the study was to assess nucleated red blood cell counts in cord
      blood in a group of asphyxiated infants, and to determine its predictive value
      for short-term outcome. A prospective case control study was undertaken on cord
      blood samples collected from fifty six term neonates with perinatal asphyxia and
      an equal number of normal appropriately matched controls for cord blood pH and
      nucleated RBC counts. Babies were followed up in nursery till discharge.
      Statistical analysis employed were ANOVA test, logistic and linear regression
      analysis. There was a significant increase in the number of nucleated red blood
      cells in cases as compared to controls. Low Apgar, cord blood pH and neonatal
      outcome correlated well with nucleated RBC counts. Nucleated red blood cell count
      at birth is a useful predictor of severity and short-term outcome of perinatal
      asphyxia.

PMID- 16295377
TI  - Economical choices in setting up a diagnostic myeloma laboratory.
AB  - In setting up a diagnostic myeloma laboratory the popular, highly automated and
      otherwise excellent choices of equipment and laboratory practices, so
      exorbitantly raise costs that the sustainability, even in large government
      hospitals in third world countries may become difficult. Based on our experience
      in a regional cancer center in India, we offer here, guidelines for carrying out
      high resolution electrophoresis, densitometry, immunofixation and urine
      concentration. We show that by simply employing well established techniques and
      doing them properly, one can get results of excellent quality at minimum cost and
      minimum dependence on costly imports.

PMID- 16295379
TI  - Mammary hamartoma: report of two cases including one in a male breast, and review
      of the literature.
AB  - Mammary hamartoma is best viewed as a "breast within a breast" and is most often
      mistaken for fibroadenoma, phyllodes tumour or lipoma. It shows an abnormal
      blending of normal breast tissue components and is cured by removal. We present
      two cases of mammary hamartoma one occurring in a male breast. Although it is
      true, that all diseases occurring in female breast can also be seen in a male
      breast, there has been no report of this condition in a male. To the best of our
      knowledge, this is the first case of mammary hamartoma occurring in a male.

PMID- 16295378
TI  - Spermatic granuloma presenting as an epididymal nodule: fine needle aspiration
      cytological findings and differential diagnosis.
AB  - Spermatic granuloma is a granulomatous lesion that presents clinically as a
      nodular lesion in the region of epididymis. There are only few documented cases
      of spermatic granuloma in the literature. Fine needle aspiration (FNA) reveals
      mixed inflammatory cells comprising of plenty of macrophages along with
      lymphocytes and scattered polymorphs in a fluidy background containing many
      spermatozoa and sperm heads. Sperm heads are also noted within macrophages. Ill
      formed to well-formed granulomas were seen in all the cases. FNA has an important
      role in the differential diagnosis of epididymal nodule as it can rule out
      malignancy and other benign cytological diagnosis like tuberculosis, acute and
      chronic epididymo-orchitis. Distinction of spermatic granulomas from the more
      common tuberculous granulomatous infection is important from the
      cytopathologist's point of view. By providing an accurate and rapid diagnosis,
      FNA prevents aggressive and potentially inappropriate surgical procedures.

PMID- 16295380
TI  - Lymphoplasmacytic lymphoma with IgA paraproteinemia mimicking Waldenstrom's
      Macroglobulinemia.
AB  - Central to the diagnosis of Waldenstrom's Macroglobulinemia is the demonstration
      of bone marrow infiltration by lymphoplasmacytic lymphoma with Ig M monoclonal
      gammopathy. We describe a patient who presented with a clinical and
      haematological picture, highly suggestive of Waldenstrom's Macroglobulinemia, but
      whose serum monoclonal immunoglobulin belonged to Ig A class. Ig A secreting
      lymphoplasmacytic lymphoma undoubtedly exist but are exceedingly uncommon and
      their relationship to Waldenstrom's Macroglobulinemia needs to be clarified.

PMID- 16295381
TI  - Angiodysplasia of cardia of stomach--a case report.
AB  - Angiodysplasia of gastrointestinal tract is still thought to be an entity of
      unknown aetiology. This lesion is most commonly observed in elderly patients
      presenting with severe and persistent iron deficiency anaemia, following occult
      blood loss or acute episodes of haematemesis. In the stomach antral vascular
      ectasia is the most common presentation. We report an autopsy case of vascular
      ectasia in the cardia of stomach in a young patient with clinical symptoms of
      anaemia as the presentation and an associated secondary hemosiderosis of liver.

PMID- 16295382
TI  - Multicystic nephroma--report of two cases.
AB  - Multicystic Nephroma (MCN) is an uncommon renal pathology, characterized by the
      presence of usually unilateral circumscribed focal lesion consisting of multiple
      thin walled cysts. The etiology and pathogenesis of multicystic nephroma is not
      clear, and it is considered as a neoplastic lesion by many authors. To the best
      of our knowledge it has not yet been reported from India. We report first two
      pediatric cases of MCN from India. Computerized Tomography (CT) scan in both the
      cases revealed a unilateral cystic lesion in the lower pole of kidney. Keeping in
      mind the age, clinical presentation and radiological appearance, a possibility of
      Wilm 's tumour with cystic change could not be ruled out preoperatively and both
      children underwent nephrectomy. Since MCN has a benign behaviour it must be
      differentiated from focal cystic neoplastic lesions, including Cystic Partially
      Differentiated Nephroblastoma (CPDN), which has a low but distinct capability for
      local recurrence, and from Wilm's tumour with cystic change. Segmental form of
      unilateral renal dysplasia also needs to be considered in the clinical and
      radiological differential diagnoses.

PMID- 16295384
TI  - Primary fibrosarcoma of the ovary--report of two cases.
AB  - The authors describe two cases of primary fibrosarcoma of the ovary in 48 years
      and 66 years old women. Patients presented with abdominal masses associated with
      pain in the first case. USG and CT scan of the abdomen revealed ovarian tumours
      involving the left side in both cases . Both underwent a total abdominal
      hysterectomy with bilateral salpingo-oophorectomy. Histological examination
      showed features of fibrosarcoma grade I and grade III respectively. A
      clinicopathological study and brief review of literature is presented.

PMID- 16295383
TI  - Severe chronic neutropenia--a case report.
AB  - Severe chronic neutropenia (SCN) is a very rare disease with around 650 people
      worldwide known to have the condition. SCN is a serous condition with a
      considerable morbidity and mortality if not treated. We hereby report a case of
      SCN which had repeated admissions to the hospital with severe neutropenia and
      high grade fever. We also review the literature elucidating some of the
      mechanisms and consequences of SCN ( e.g: the neutrophil elastase gene mutations
      and the risk of progression to myelodysplasia and acute leukemia) and the role of
      granulocyte-colony stimulating factor.

PMID- 16295385
TI  - Sarcomatoid renal cell carcinoma with osteosarcomatous differentiation--a case
      report.
AB  - A rare case of sarcomatoid renal cell carcinoma (RCC) with predominantly
      osteosarcomatous differentiation occurring in a 36-year-old male is reported.
      Immunohistochemistry excluded the possibility of primary osteosarcoma of the
      kidney.

PMID- 16295386
TI  - Phosphaturic mesenchymal tumor: a case report.
AB  - Osteomalacia induced by tumor is a rare phenomenon in which the resection of
      tumor is followed by dramatic amelioration of clinical signs and symptoms. We
      hereby report a case of a 66 years old male who presented with features of
      osteomalacia in which the characteristic clinical presentation was associated
      with the phosphaturic mesenchymal tumor, mixed connective tissue variant. The
      case is reported for its rarity.

PMID- 16295387
TI  - Primary lymphoma of the liver--a case report.
AB  - A case of primary lymphoma of the liver who presented with a rapidly increasing
      mass in the right upper abdomen is reported. Histological examination confirmed
      the diagnosis of diffuse, intermediate cell type of Non Hodgkins Lymphoma and was
      identified as "B" cell type by the use of specific monoclonal antibodies. The
      case is being reported for its rarity and the clinical importance of recognizing
      such cases because of excellent prognosis.

PMID- 16295388
TI  - Primary signet ring carcinoma of the large bowel--a case report.
AB  - Primary signet ring carcinoma of the colon and rectum is a rare neoplastic
      disease. The first case was reported by Laufman and Saphir in 1951. The patients
      have extensive disease at the time of diagnosis and the prognosis is extremely
      poor. Thus though difficult early diagnosis and curative operation are important.

PMID- 16295389
TI  - Partial duplication of head--a rare congenital anomaly.
AB  - Duplication of notochord results in rare congenital anomalies like double headed
      monsters, with or without trunk/limb duplication, depending upon the extent of
      notochordal abnormality. Here we describe the morphological abnormalities in a
      case of partial duplication of cranial structures with fusion of the two. Autopsy
      findings suggest that the bifurcation of the neural tube took place around 4th to
      6th week of gestation. There are only few reports in English literature
      describing the autopsy findings of such an anomaly, which is termed as Diprosopus
      triophthalmus in the modern literature.

PMID- 16295390
TI  - Insulinoma--a case report.
AB  - Insulinoma is a rare pancreatic endocrine tumour characterised by
      hyperinsulinemic hypoglycemia. It is important to surgically remove this tumour
      as it can cause potentially lethal hypoglycemia. We report a case of insulinoma
      presenting with unconsciousness following repeated episodes of inability to arise
      from sleep and convulsions. Biochemical investigation revealed hypoglycemia and
      hyperinsulinemia. The diagnosis of Insulinoma is often delayed due to
      misattribution of symptoms to psychiatric or neurological disorders. In this
      case, same delay lead to fatal outcome for this patient.

PMID- 16295391
TI  - Fatal disseminated cryptococcosis in a HIV negative elderly Indian woman--an
      early diagnosis by polarizing microscopy.
AB  - An elderly HIV negative woman with disseminated cryptococcosis is reported. The
      clinical presentation was unusual. Rapid diagnosis is possible if Maltese crosses
      are demonstrated on polarizing microscopy of tissue sections or smears. Cutaneous
      involvement in cryptococcosis is uncommon, however when present, can be a
      valuable and relatively easily available source of material from which
      Cryptococci can be demonstrated.

PMID- 16295392
TI  - Clear cell mesothelioma of the testis with deciduoid areas--a case report.
AB  - We report a clear cell type of primary purely epithelial malignant mesothelioma
      with focal deciduoid features in the para-testis of a 75 year old man. This
      variant requires ancillary studies like immunohistochemistry for confirmation.
      Awareness of this variant is required to avoid misdiagnosis and treatment as
      either metastasis from a renal cell carcinoma or as a germ cell tumor. A
      diagnosis of mesothelioma must be ruled out in elderly patients with epithelial
      looking tumor especially if the serum germ cell tumor markers are within normal
      range.

PMID- 16295393
TI  - Diffuse hyperplastic oncocytosis of parotid gland: a case report.
AB  - Oncocytic tumors of salivary glands are rare. Diffuse oncocytosis is the rarest
      lesion among 3 principal groups of oncocytic lesions as classified by WHO. Only
      seven cases have been previously reported in the literature. We report a case of
      diffuse hyperplastic oncocytosis of the parotid gland in a 63-year-old male with
      a brief review of literature. To the best of our knowledge this is the first case
      from Indian subcontinent.

PMID- 16295395
TI  - Breast hamartoma associated with pregnancy--a case report.
AB  - Hamartoma of the breast is an uncommon tumor like condition constituting only 3.9
      to 4.8 % of benign breast tumors. We wish to report clinical, cytological,
      cytological histological findings of breast hamartoma with pregnancy

PMID- 16295394
TI  - Testicular tumour with features of sex cord tumor with annular tubules associated
      with cryptorchidism and infertility--a case report.
AB  - Sex cord tumor with annular tubules (SCTAT) is a rare tumor seen in the ovary
      usually associated with Peutz-Jeghers syndrome. Testicular SCTAT are more
      infrequent and only four such cases have been reported in the literature. A 28
      year-male presented with infertiliy. He had a history of orchiopexy 10 years back
      for right-sided inguinal testes. A right testicular biopsy done to investigate
      the cause of infertility revealed testicular atrophy with a focus suspicious of
      SCTAT. The right-sided orchiectomy revealed two firm nodules of 0.5 and 0.2 cms
      of SCTAT and sertoli cell nodule (SCN) respectively on microscopy. He did not
      have any features of Peutz-Jeghers or any other dysgenetic syndrome. He is
      asymptomatic after follow up of 26 months. This is the fifth case of testicular
      SCTAT and the first with SCN.

PMID- 16295396
TI  - Bacteremia due to Rhodococcus equi--a case report.
AB  - Rhodococcus equi (R. equi) primarily causes zoonotic infections affecting grazing
      animals and is an unusual cause of infection in immunocompetent human beings. We
      report a case of bacteremia due to R. equi a rare isolate in a child suffering
      from protein energy malnutrition

PMID- 16295397
TI  - Bacteriuria in patients with gallbladder and biliary tract diseases.
AB  - Urinary tract infections (UTI) are important hospital acquired entities,
      resulting in bacteriuria indicated by the presence of significant numbers of
      bacteria in the urine. This study examined the prevalence of bacteriuria in our
      patients with gallbladder diseases. Three hundred and forty eight patients with
      various gallbladder (GB) diseases were enrolled in our study. Routine
      bacteriological cultures of midstream urine specimens were done. Significant
      bacteriuria was defined as the growth of 105 or more organisms in pure culture
      per milliliter of urine. Forty four (12.6%) of the patients (18 symptomatic; 26
      asymptomatic) showed bacteriuria. Escherichia coli was the predominant isolate
      followed by Klebsiella pneumoniae, Enterobacter, Pseudomonas aeruginosa,
      Enterococci and several others. Thus UTI is also a frequent concomitant of gall
      bladder diseases and is a sign of the fact that kidneys are in a condition
      endangered by pyelonephritis.

PMID- 16295398
TI  - Histopathological and ultrastructural alterations of induced Yersinia
      enterocolitica infection in mice.
AB  - Yersinia enterocolitica is an enteric bacterium and infections by this organism
      are mostly foodborne. It has been implicated to cause enterocolitis, terminal
      ilitis. diarrhoea, mesenteric lymphadenitis and arthritis in man. Due to paucity
      of information regarding histopathological and specially ultrastructural
      alterations in tissues affected, this study was planned with mice as the
      experimental model. Nine pathogenic Y.enterocoliticaisolates were used to infect
      80 albino mice by oral and intraperitoneal route. Pathological alterations were
      studied by light and electron microscopy. Histopathological examination of
      intestines showed severe edema, purulent enteritis, goblet cell hyperplasia
      infiltration of mononuclear cells, thickening of mucosa and necrosis of the tips
      of villi. Liver showed congestion, hepatocellular degeneration and necrosis,
      atrophy of hepatocytes and microabcesses. The lungs revealed congestion, edema,
      haemorrhage and purulent ronchopneumonia, while kidneys showed mild necrotic
      changes and bacterial emboli in glomeruli. Ultrastructural changes were
      indicative of mitochondrial degeneration and their loss in kidneys, membranous
      degeneration with formation of myelin figures in lungs and disorganization,
      disruption and bleb formation of microvilli in intestines. Y.enterocolitica
      caused significant histopathological and ultrastructural alterations in
      experimentally infected mice. Variation in pathogenicity of different strains of
      Y.enterocolitica was also observed.

PMID- 16295399
TI  - An in vitro evaluation of antibiotic combinations for urinary tract infections in
      patients with diabetes mellitus.
AB  - This prospective in-vitro study evaluates the synergistic potential of various
      antibiotic combinations against resistant pathogens isolated from urinary tract
      infections (UTIs) in patients with diabetes mellitus. Antibiotic combinations
      using the microtiter checkerboard method showed that overall, synergy could be
      seen in 41.86%-67.44% cases amongst the five different antibiotic combinations
      studied against the four predominant resistant pathogens namely Escherichia coli,
      Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella ozaenae. The
      checkerboard synergy studies showed that 69.23% of the S. aureus strains tested
      were synergistically inhibited by the combination of ofloxacin + cefotaxime
      [OF+CF], 83.33% of the E. coli strains and 75% of the K. ozaenae strains were
      synergistically inhibited by the combination of amikacin + cefotaxime [AK+CF],
      while 58.33% of the P. aeruginosa strains were synergistically inhibited by the
      combination of amikacin + piperacillin [AK+PP].

PMID- 16295400
TI  - Overexpression for commercial production of recombinant human insulin as A-chain
      and B-chain fusion protein in Escherichia coli through genetically engineered
      plasmids.
AB  - The construction of expression vectors encoding either the human insulin A- or B
      chains fused to a synthetic peptide and the temperature-induced expression of the
      recombinant genes in Escherichia coli are reported. Using this two-chain approach
      we also describe the separate isolation of the insulin A- and B-chains from
      inclusion bodies and their subsequent assembly into native human insulin. The
      expression yields about 600 mg of the insulin B-chain per litre of culture. Under
      similar conditions the expression yield of the insulin A-chain corresponds to
      approximately 500 mg per litre of culture. This is the highest yield from shake
      flask experiments.

PMID- 16295402
TI  - Protective effect of various chemicals on the impairment of sperm motility by
      Staphylococcus aureus.
AB  - In female genital tract spermatozoa remain active for several days, however,
      their activity is of much shorter duration if they remain in the seminal fluid
      outside the body. Majority of spermatozoa cease to move within first 24 hrs. This
      may be due to presence of bacteria or excretion of bacterial toxic products; To
      check whether the addition of certain chemicals can enhance the motility of
      spermatozoa in presence of bacteria, in vitro studies were conducted. 72h old
      culture supernatant of Staphylococcus aureus isolated from infertile male causing
      100% immobilization of spermatozoa was incubated with semen samples in presence
      of various chemicals. The results showed that sodium chloride, magnesium sulfate,
      sodium citrate, folic acid, nicotinic acid, H2O2 and glutathione had protective
      effect on the impairment of motility. This study implicates that even if bacteria
      causing 100% immobilization of spermatozoa are present, supplementation of
      certain chemicals is beneficial.

PMID- 16295401
TI  - Development and evaluation of an enzyme immunoassay for rapid diagnosis of rabies
      in humans and animals.
AB  - The presently advocated tests for rapid diagnosis of rabies such as fluorescent
      antibody test (FAT) is expensive and requires expertise to carry out and
      interpret the results. In this study we have developed and evaluated a simple
      enzyme immuno-assay (EIA) to detect rabies antigen in the brain specimens of
      animals and humans. We have also evaluated the utility of this test in ante
      mortem diagnosis of human rabies. The brain homogenates of suspected rabid
      animals (n=250), humans (n=16) and clinical samples like saliva (n=16) and
      cerebrospinal fluid (CSF, n=16) applied on to ELISA plates coated with rabies
      antinucleoprotein antibody and the absorbed rabies nucleoprotein antigen was
      detected using biotinylated anti-nucleoprotein antibody followed by treatment
      with streptavidin peroxidase conjugate and colour development with OPD. Rabies
      infected and normal mouse brain homogenates were used as positive and negative
      controls respectively. The results of this test was evaluated with fluorescent
      antibody technique (for brain samples) and mice inoculation test (for saliva and
      CSF samples). A distinct dark brown color was seen in positive control and all
      positive samples and there was no color development in negative control and
      samples. The concordance between FAT and EIA was 98.4%. With brain samples, 83.3%
      with saliva and 91.6% with CSF samples. The specificity of the test was found to
      be 100%. It can be concluded that the EIA described here is a sensitive, specific
      and rapid test for post mortem diagnosis of rabies in animals and humans. The
      utility of this test for ante mortem diagnosis of rabies needs to be further
      evaluated.

PMID- 16295403
TI  - Indirect immunofluorescence test: role in seroepidemiology and serodiagnosis of
      herpes simplex viral infections.
AB  - A study was carried out to find out a) the seroprevalence of herpes simplex viral
      infections (HSV) in and around Chandigarh city, North India and the probable age
      of acquisition of infection; b) the usefulness of salivary antibody detection in
      seroprevalence studies; c) role of HSV immunofluorescence antibodies in the sero
      diagnosis of herpes simplex encephalitis (HSE) patients. Single blood samples
      from 306 and paired blood and saliva samples from 48 apparently healthy
      individuals as well as paired blood and C.S.F. samples from 50 clinically
      suspected patients of HSE were included in the study proper. The subjects
      belonged to <6 months to > 30 years age group. Serum, saliva and C.S.F. samples
      were subjected to in house standardized indirect immunofluorescence test for the
      detection of HSV antibody. The overall seropositivity was 59.3%, which increased
      from 37.5% in children less than 10-years of age to 88.9% in individuals above 30
      years of age (p<0.001). The maximum titer in less than 10 years children and
      above 10 years subjects were found to be 40 and 160 respectively. The difference
      in percentage positivity of HSV antibody in these groups was statistically
      significant (p<0.001). No difference in the seroprevalence rate was observed
      between different socio-economic groups and sex. Saliva in comparison to serum
      showed a sensitivity of 44% and specificity of 100% for the detection of HSV
      antibodies. Among the suspected HSE patients 4 (8%) could be serologically
      confirmed. This study indicated the endemicity of HSV infection in this locality.
      Indirect immunofluorescence test could detect intrathecal HSV antibodies in 8% of
      suspected HSE patients proving it to be a very useful rapid serodiagnostic tool.
      However, saliva testing showed limited sensitivity in HSV sero surveys.

PMID- 16295404
TI  - Significance of coagulase negative staphylococci in neonates with late onset
      septicemia.
AB  - Present study was undertaken for establishing significance of coagulase negative
      staphylococci isolated from cases of late onset neonatal septicemia. 660 neonates
      admitted to NICU with clinical suspicion of late onset septicemia, over a period
      of nine months, were included in study. After skin preparation 1.5-ml blood for
      culture was collected from two different sites by venipuncture and each was
      inoculated into a blood culture bottle. All CONS thus isolated were further
      analysed. Laboratory criteria for significant CONS bacteremia was defined as
      recovery of CONS with in 48 hours of specimen collection from both sites of a
      blood culture set that displayed uniform antibiotic susceptibility and
      biochemical reactions. Due to technical difficulties two samples for blood
      culture were obtained only from 338 cases, CONS were recovered from 52 (22.7%)
      cases; only 13 (25%) were considered significant. Only single blood sample was
      available from remaining 322 subjects and CONS were recovered from 36/322
      (24.3%). CONS isolation rate was similar in both subject groups. Using double
      specimen protocol we found majority of CONS recovered from neonates, to be
      probable contaminants. Recovery of CONS from blood of a septicemic neonate needs
      to be viewed with caution since not all of them are true bacteremic agents.

PMID- 16295405
TI  - Modified blood supplemented Lowenstein Jensen medium improves recovery of
      mycobacteria from sputum samples.
AB  - Lowenstein Jensen medium containing 3% human blood in CPDA anticoagulant was
      compared with plain LJ medium for mycobacterial growth using 565 sputum samples.
      Mycobacterial growth appeared on both the media in case of 148 samples. However,
      growth was faster by one week and colony size larger over blood supplemented LJ
      in 53 of the 145 culture positives. Additional 12 samples which showed no growth
      on plain LJ could grow only on LJ supplemented with blood. While 3 samples
      revealed scanty growth on plain LJ alone. The experience suggests that two LJ
      slants; one plain and the other supplemented with blood be in inoculated
      routinely to increase speed of growth and recovery of mycobacteria from clinical
      samples.

PMID- 16295406
TI  - Endometrioid variant of yolk sac tumour.

PMID- 16295407
TI  - Non-secretory plasma cell leukemia: a rare hematological malignancy.

PMID- 16295408
TI  - Fluoroquinolone resistance from a transferable plasmid in Acinetobacter
      calcoaceticus.

PMID- 16295409
TI  - High level resistance in gram negative bacilli.

PMID- 16295410
TI  - In reference to "Hepatoblastoma--three cases".

PMID- 16295411
TI  - Gravid adult filarial worm in fine needle breast aspirate masquerading as
      carcinoma.

PMID- 16295412
TI  - Microfilaria of Wuchereria bancrofti in cervicovaginal smear.

PMID- 16295413
TI  - Fine-needle aspiration (FNA) cytology diagnosis of small round cell tumors: value
      and limitations.
AB  - Small round cell tumors (SRCTs) are a group of malignancies (non-Hodgkin
      lymphoma, neuroblastoma, retinoblastoma, hepatoblastoma, nephroblastoma,
      rhabdomyosarcoma, small cell anaplastic carcinoma, Ewing sarcomal peripheral
      neuroectodermal tumor, and desmoplastic small round cell tumor), characterized
      both cytologically and histologically by a predominantly small round to oval, and
      relatively undifferentiated cells. Together they form a formidable group and an
      overwhelming majority of childhood malignancies. The patients may present in
      later (inoperable) stage with huge intrathoracic and intraabdominal mass, when
      chemotherapy and/or radiation therapy may be the first or only line of treatment.
      As a less invasive procedure fine needle aspiration (FNA) cytology has definite
      advantage over surgical excision biopsy to arrive at a tissue diagnosis before
      initiation of therapy. Because of the morphologic similarities, the SRCTs may
      pose a differential diagnostic problem in the practice of clinical cytology,
      especially when they are poorly differentiated. Important cytomorphological
      features, which help in the identification of various SRCTs include completely
      dissociated cell population and lymphoglandular bodies (cytoplasmic fragments) in
      non-Hodgkin lymphoma (NHL), eosinophilicfibrillar material and Homer-Wright
      rosettes along with cellular processes in neuroblastoma, acinar formation in
      hepatoblastoma, blastema cells with tubular differentiation in nephroblastoma,
      tadpole shaped cells in embryonal rhabdomyosarcoma, extreme nuclear molding and
      perinuclear blue inclusion in small cell anaplastic carcinoma (SCAC), irregular,
      punched out and large cytoplasmic vacuolations due to glycogen in Ewing sarcoma,
      and sheets of undifferentiated small round cells surrounded by collageneous
      stroma in desmoplastic small round cell tumor (DSRCT). Some of these features
      such as nuclear molding, rosette, and acinar formation are noticed in more than
      one type of SRCTs. Moreover, the characteristic cytomorphological features may be
      present in 70-80% cases and for categorization of the remaining cases,
      contribution from ancillary studies is essential. It is suggested that
      cytomorphological features along with one or more of the parameters such as
      special stains (cytochemistry), immunocytochemistry (ICC), electron microscopy
      (EM), tissue culture, DNA ploidy, karyotype and molecular analysis can increase
      the diagnostic accuracy of SRCTs. However, these facilities may not be available
      in all the laboratories, especially in the developing countries, and even if
      available in a limited form, a tissue diagnosis has to be offered often by FNA
      cytology based on morphological features, as a life saving measure in seriously
      ill patients before the results of ancillary studies are finalized.

PMID- 16295414
TI  - Diagnostic utility of fine needle non-aspiration cytology versus fine needle
      aspiration cytology in breast masses.
AB  - Fine needle aspiration cytology (FNAC) and fine needle non-aspiration cytology
      (FNNAC) techniques were studied in 145 cases of breast masses. All the needle
      sampling procedures were done by single operator. The samples were assessed
      cytologically and evaluated using five parameters i.e. background blood or clot,
      amount of cellular material, degree of cellular degeneration, degree of cellular
      trauma and retention of appropriate architecture. Differences between all the
      individual parameters as observed in FNAC and FNNAC smears were insignificant.
      After evaluation of FNNAC and FNAC on the basis of these scores, greater number
      of diagnostically superior samples were obtained by FNNAC; however by FNAC more
      number of diagnostically adequate smears were observed. This difference was
      statistically significant. The number of unsuitable smears were also more by
      FNNAC technique.

PMID- 16295415
TI  - Utility of white blood cell suspect flags and histogram pattern in the detection
      of acute leukemia by Advia-60 automated hematology analyzer.
AB  - Blood samples from patients with acute leukemia, when analyzed with automated
      hematology counters, tend to introduce inaccuracies in the automated differential
      count and can cause diagnostic confusion without providing definite clues to the
      presence of abnormal cells. We designed this study to assess the utility of white
      blood cell (WBC) flags and histogram pattern generated by Advia-60 automated
      hematology analyzer in the recognition and categorization of acute leukemia. Data
      printouts of 31 newly diagnosed cases of acute leukemia, 22 with acute myeloid
      leukemia (AML) and 9 with acute lymphoblastic leukemia (ALL) were reviewed. All
      cases of AML and ALL generated the WBC suspect blastflag M2 associated with two
      of the non blast suspectflags G1 and G2. Among the cases of AML, 95.5% of the WBC
      histogram patterns were definitive of the presence of abnormal cells and were
      indicative of the myeloid nature of cells. Only 44.4% of the histograms in the
      cases of ALL could be definitive of the presence of abnormal cells and 33.3% were
      indicative of their lymphoid nature. Significantly, 55.5% of the histograms in
      ALL were normal. The false positives for both AML and ALL were 10.5% when only
      WBC flagging was considered and were reduced to 0.05% when the flags were
      combined with histogram patterns for interpretation. Combined flagging and
      histogram recognition can be of aid in identifying cases of acute leukemia and
      the morphologist can then assess these samples further. This ensures that cases
      of acute leukemia, especially in high output laboratories, are not inadvertently
      missed.

PMID- 16295417
TI  - Sclerosing stromal tumour of ovary--a clinicopathological and immunohistochemical
      study of five cases.
AB  - We describe the clinicopathological and immunohistochemical findings in five
      cases of sclerosing stromal tumours of ovary and compare our findings with other
      reported cases of this uncommon tumour and with fibromas and thecomas which they
      may mimic.

PMID- 16295416
TI  - Pathological spectrum of cytomegalovirus infection of renal allograft recipients
      an autopsy study from north India.
AB  - This is a retrospective study of autopsy material to highlight the histo
      morphological changes in cytomegalovirus (CMV) infection amongst renal allograft
      recipients. Nineteen out of 80 patients (23.75%) autopsied during a seventeen
      year period (1985-2001) had CMV infection. Pulmonary infection was present in 14
      out of 19 cases of which four had isolated lung involvement. Likewise, there were
      two cases each of isolated oesophageal and renal involvement; one case with
      isolated colonic involvement. The other 10 cases had multi-organ involvement and
      the organs involved were kidneys (4), esophagus (6), stomach (1), colon (5),
      adrenals (3), pancreas (3), liver (1) and spleen (1). Pulmonary infection with
      CMV was associated with acute pneumonitis in 3 cases and lymphocytic interstitial
      pneumonitis in 9 instances. Four out of 6 cases had acute tubulo-interstitial
      nephritis induced by CMV and only two cases had no significant inflammatory
      response. Glomerular involvement in the form of CMV inclusions in the glomeruli
      was present in only one case. Gastrointestinal CMV infection (15) presented as
      acute necrotizing ulceration because of predominant endothelial involvement. Post
      transplant survival period varied from one month to three years, with majority
      (14) of the patients having survived for less than one year.

PMID- 16295419
TI  - Tumour angiogenesis and C-myc expression in breast carcinomas.
AB  - Angiogenesis in tumors has been widely studied and has been considered to be a
      prognostic factor particularly in breast carcinomas. The myc family of proto
      oncogenes has shown an amplification in breast carcinomas. The aim of this study
      was to assess MVD (micro vessel density) and the expression of c-myc in invasive
      breast carcinomas. Formalin fixed, routinely processed, paraffin embedded tissue
      was stained with H&E for classification and grading according to the Nottingham
      modification of Bloom and Richardson criteria. Immunohistochemical staining using
      primary antibody against F VIII antigen and anti C-myc were carried out. LSAB
      method was employed with AEC as chromogen and Gill's Haematoxylin as counter
      stain. Micro vessels were counted and positivity indicated by a cherry red
      staining in the cytoplasm of the tumour cells. Grades I, II and III showed 12.22
      %, 20.9% and 24.5 % positivity of micro vessel density (MVD). Fifty percent of
      Grade 1, 69.2 % of Grade II and 24.5 % of Grade III tumours expressed c-myc
      proteins. In our study we found a positive association between tumour grade and
      micro vessel density, signifying a poor prognosis for tumours with high MVD. C
      myc expression also showed a positive association with increasing grade.

PMID- 16295418
TI  - FAB classification of leukemia: a cytochemical study.
AB  - The reproducibility of FAB classification for acute leukemia was assessed using
      the modified criteria of the FAB classification. Peripheral smears and bone
      marrow smears from 36 cases of acute leukemia stained with May-Graunwald-Giemsa
      were used for this purpose. Cytochemical stains used for this purpose were
      myeloperoxidase (MPO), Sudan Black B (SBB), Periodic acid Schiff's (PAS) and
      Alpha-naphthyl acetate esterase (ANAE). The concordance with morphology alone was
      75% which improved to 92% when cytochemistry was included.

PMID- 16295420
TI  - Radiation-related cytological changes in oral malignant cells.
AB  - Carcinoma of the oral cavity constitutes approximately 40% of overall malignant
      tumours in India, with an incidence of about 56,000 cases per year. Radiation
      responses in oral cancer cells by cytology have not been extensively studied. 102
      patients with squamous cell carcinoma of the oral cavity treated by fractionated
      radiotherapy were studied. Serial scrape smears were taken from each tumour
      before and after irradiation. The abnormal nuclear counts per 1000 malignant
      cells were 1.6 and 14.1(p<0.001) for micronucleation, 0.9 and 5.5 (p<0.001) for
      nuclear budding, 7.6 and 28.1(p<0.001) for binucleation and 2.4 and 11.7(p<0.001)
      for multinucleation respectively. The study showed a significant rise in
      radiation induced cytological responses. In addition, radiation changes observed
      included abnormal and incomplete divisions of a nucleus, fibroblast like
      appearance cells, and enlargement of nuclear size as well as cytoplasmic
      granulation. These changes may have an important role to play in understanding
      the mechanism of cell killing after radiotherapy.

PMID- 16295421
TI  - Hemophagocytic syndrome in malaria and kala-azar.
AB  - Hemophagocytic syndrome is a clinicopathological entity characterized by systemic
      proliferation of cells of the monocyte-macrophage-histiocytic lineage associated
      with fever, cytopenias, hepatosplenomegaly, lymphadenopathy and coagulopathy. Two
      forms of the syndrome have been described-familial hemophagocytic
      lymphohistiocytosis (FHL) of infants and reactive hemophagocytosis syndrome (RHS)
      encountered at any age. The underlying diseases are heterogenous which include,
      systemic lupus erythematosus and infections- bacterial, viral, fungal and
      parasitic. Mechanisms of RHS remain unclear, but cytokines may play a role. Risk
      factors associated with death are worsening anemia, thrombocytopenia during
      treatment, presence of DIC, and increase in serum ferritin and a-2 microglobulin
      and jaundice. We discuss the peripheral blood and bone marrow findings in 14
      cases RHS with associated Kala-Azar (9 cases) and malaria (plasmodium vivax-2,
      plasmodium falciparum-3 cases). Three patients of Kala-azar expired- two due to
      hemorrhagic shock and one as a result of antimony related myocarditis.

PMID- 16295422
TI  - Myxomatous stromal changes and necrosis of bone marrow--a retrospective study of
      3 years.
AB  - Myxomatous stromal changes and bone marrow necrosis (BMN) are uncommon histologic
      findings. These changes have been found in various conditions like disseminated
      carcinomatosis, postchemotherapy cases, chronic infections, infiltrative
      disorders of the marrow etc. The present study is a retrospective study of 3
      years (Jan, 1999 to Dec. 2001) from Deptt. Of Hematology, Postgraduate Institute
      of Medical Education and Research (PGIMER), Chandigarh (India). During this
      period, 3740 bone marrow samples were examined. Myxomatous stromal changes and
      bone marrow necrosis were noted in 0.43% (16/3740) and 0.45% (17/3740) samples
      respectively. In addition to common causes of myxomatous stromal changes and bone
      marrow necrosis as described in the literature, this study highlights the
      association of these conditions with some of the rarer entities like
      hyperoxalosis, leishmaniasis, parvovirus induced marrow aplasia and cryptococcal
      infection. There is paucity of such associations in the literature.

PMID- 16295424
TI  - Histomorphology of multiple myeloma on bone marrow biopsy.
AB  - In a retrospective study, 49 bone marrow biopsies (BMB) of patients with multiple
      myeloma (MM) were studied for its role in diagnosis and to determine histological
      parameters of prognostic significance. Sections were analyzed by 2 observers and
      classified according to: 1. Cytological grading according to differentiation of
      the neoplastic cells as plasmacytic, pleomorphic and plasmablastic. 2. Volume of
      infiltration: quantitating the percentage of myeloma cells in the biopsy. 3.
      Pattern of neoplastic infiltration. The overall marrow cellularity, presence of
      marrow fibrosis, micro-osteolesions and normal haematopoeisis were also studied.
      The bone marrow biopsy (BMB) was diagnostic for myeloma in five cases, where the
      aspirates were hypocellular: four had early myeloma and one had extensive marrow
      fibrosis. The pattern of infiltration was interstitial in 19 cases (39%), nodular
      in 19 cases (39%), and diffuse in 11 cases (22%). In majority of the cases (49%),
      the cell type was plasmacytic (24 cases), plasmablastic in 10 cases and
      pleomorphic in 15 cases. All cases of poorly differentiated cell type
      (plasmablastic) had a diffuse or nodular pattern of infiltration, whereas
      majority of the well-differentiated cell type had an interstitial pattern. The
      plasma cell burden in biopsy i.e the volume of infiltration was <10% in 8 cases,
      <50% in 19 cases and >50% in 22 cases and was used for histological staging of
      MM. Fibrosis was present in 30% of cases. Follow up was available in 11 cases,
      and cases with poorly differentiated myeloma, diffuse pattern of infiltration and
      dense fibrosis had survival less than one year. Cases of well differentiated
      myeloma, interstitial pattern of infiltration and plasma cell load less than 20%
      with absence of fibrosis had a more than 5-year survival. Different series have
      quoted that all these histological parameters provide valuable prognostic
      information, wherever other modalities like beta 2 microglobulin and IL-6 levels,
      etc are not available. The effects of therapy can also be monitored by sequential
      biopsies.

PMID- 16295423
TI  - Role of proliferative markers in prostatic lesions.
AB  - Prostatic lesions on routine H&E stain sometimes cause diagnostic dilemma
      specially in premalignant lesions like A.A.H. and P.I.N. Proliferative markers
      (AgNOR, P.C.N.A) are of great help in this grey zone. Total 50 cases studied and
      provisional diagnosis after HIE stain revealed that 37 cases were B.H.P., 5 cases
      were A.A.H., 1 case was P.I.N and 7 cases were adenocarcinoma. Proliferative
      marker study revealed AgNOR count of B.H.P as (0.4 -2.5)/cell, of A.A.H as (1.5
      3.2)/cell, of P.I.N as 4.8/cell and adenocarcinoma as (4.3-5.4)/cell. P.C.N.A
      index of B.H.P was (2-8)%, of A.A.H (17-35)%, of P.I.N 40% and of carcinoma (54
      82)%. Proliferative marker study was of great help in distinguishing between
      benign and malignant and specially premalignant lesions like A.A.H and P.I.N,
      where routine histopathology diagnosis was confusing. In the study, P.C.N.A was
      found to be superior to AgNOR since the values for interpretation was wider.

PMID- 16295425
TI  - Bone marrow biopsy in Hodgkin's disease.
AB  - Bone marrow biopsies of 58 untreated patients with Hodgkin's disease were
      evaluated. Marrow involvement was seen in 36.2 % cases. Positive marrow biopsies
      were seen mainly in patients with clinical stages III and IV. Bone marrow
      involvement was most common in patients with less than 15 years of age and in
      males. HD patients with mixed cellularity had highest incidence of marrow
      involvement while none of the patients with lymphocytic predominance showed BM
      involvement. Focal infiltration was found to be more common. Bone marrow
      aspiration smears were negative in majority of cases with positive marrow
      biopsies. Thus BM trephine biopsy is a simple tool for assessment of disease
      spread.

PMID- 16295426
TI  - Utility of dystrophin and utrophin staining in childhood muscular dystrophy.
AB  - To determine the utility of dystrophin and utrophin staining in the differential
      diagnosis of childhood muscular dystrophy. Fifty muscle biopsies of
      histologically confirmed cases of childhood muscular dystrophy, below 16 years of
      age, were stained immunohistochemically for dystrophin and utrophin. All the 30
      muscle biopsies of patients with Duchenne muscular dystrophy (DMD) showed all or
      majority of muscle fibers deficient for dystrophin and positive for utrophin. In
      the 4 female DMD carriers there was mosaic pattern of staining for dystrophin and
      reciprocal positivity for utrophin. All the muscle biopsies of patients with
      other childhood onset muscular dystrophies were positive for dystrophin and
      negative for utrophin. This study shows that dystrophin staining differentiates
      DMD and DMD carriers from other childhood muscular dystrophies and utrophin
      staining is of no added value. Utrophin up-regulation may compensate for
      structural deficiency in dystrophic muscle.

PMID- 16295427
TI  - Langerhans' cell histiocytosis: a clinicopathological study of 50 cases.
AB  - To analyze the clinicopathologic features and outcome of patients with Langerhans
      cell histiocytosis (LCH). Fifty cases of LCH accrued over a 15-year period were
      analyzed and classified as having unifocal, multifocal, or multisystem disease.
      Events regarding progression, relapse, or death were noted. The 50 cases
      comprised of 34 men and 16 women. 92% of the patients were less than 15 years of
      age and 46% were less than 2 years. Involvement by LCH was unifocal in 22,
      multifocal in 8, and multisystem in 20. Bone was the commonest site (92%),
      followed by lymph node (30%). The histological features were relatively uniform
      regardless of the clinical severity, and consisted of Langerhans cells,
      eosinophils, histiocytes, plasma cells, giant cells and fibrosis. The treatment
      consisted of surgery, chemotherapy, and/or radiotherapy. Response to treatment
      was poor in patients with multisystem disease. The histology of LCH is very
      characteristic and patients with age less than 2 years are more likely to have
      increased risk or morbidity and mortality, due to widespread disease.

PMID- 16295428
TI  - Fine needle aspiration diagnosis of tuberculous mastitis.
AB  - Fine needle aspiration cytology has become the first choice in diagnostic
      procedures in the management of a variety of breast diseases. The technique can
      be successfully used to diagnose granuloma in breast aspirates and to demonstrate
      the presence of acid-fast bacilli. Tuberculosis is rampant in developing
      countries and patients are prescribed antituberculous therapy on the basis of
      finding granuloma in breast aspirates without a culture report. In our practice,
      this principle has been followed with excellent results. In our experience, this
      technique was reliable and reproducible in diagnosing tuberculous mastitis. We
      report on the cytomorphological findings of this uncommon but important disorder.

PMID- 16295429
TI  - Voluntary donors-need for a second look.
AB  - Voluntary non-remunerated blood donation is the source of the safest blood supply
      to the transfusion service. In the Indian set up where voluntary donations are
      fewer and poorly structured, safety of blood could still be compromised. This
      study was carried out to find out the seroprevalence of transfusion transmitted
      diseases among replacement and voluntary donors. A retrospective study of
      replacement and voluntary donors over a three and a half year period was carried
      out and the seroprevalence for human immunodeficiency virus (HIV), hepatitis B,
      hepatitis C, syphilis and malaria was noted. A total of 41122 donors were studied
      comprising of 94.7% replacement and 5.3% voluntary donors. The prevalence of
      transfusion transmitted diseases was marginally higher among voluntary donors
      (3.3%) as compared to replacement donors (2.9%). All cases of HIV were seen in
      the replacement donors while the figures for hepatitis B and C were marginally
      higher in the voluntary donors (p>0.05). Voluntary donations in our study were
      not voluntary in the real sense. There is a need to work on building a stronger
      voluntary donor base and to create awareness among the populace in order to
      gradually abolish the replacement donations; thereby ensuring the safety of blood
      and its products.

PMID- 16295430
TI  - Modified H & E staining technique for fine needle aspiration cytology (FNAC)
      smears.
AB  - Papanicolaou (Pap) staining procedure has achieved worldwide acceptance in
      cytology practice due to its crisp cytological details. There are many centres or
      private laboratories in our country which cannot fulfill the economic requirement
      of Pap staining and hence employ comparatively cheaper haematoxylin and eosin (H
      & E) stain. Although routine H & E cannot replace Pap, this study is an attempt
      to modify H & E staining that would offer comparable diagnostic results. The
      present study is restricted to FNAC material from palpable lesions i.e.breast and
      lymph nodes. For this purpose 50 lymph nodes ( LN) and 18 breasts were aspirated.
      Out of two fixed smears, 1 was stained by Pap technique for routine reporting and
      other by modified H & E method which was examined and reported by other
      pathologist, Dr. Sangeeta B. Desai ( SBD) The diagnosis of both the techniques
      were compared. Emphasis was also given on cytomorphological characteristics. Out
      of fifty lymph node aspirates from various sites, no diagnostic discrepancy was
      observed in 46 cases. Three out of 4 had sampling errors whereas, poor nuclear
      staining was noticed in a single case. Out of eighteen breast aspirates
      concordant diagnosis was achieved in 16 cases. Out of two discrepant diagnosis 1
      was due to sampling error, and the other was an interpretative error. All the
      cases were confirmed histologically. In conclusion, modified H & E staining is
      useful for common sites of aspirations of superficial lesions.

PMID- 16295431
TI  - Adrenocortical oncocytoma--a case report.
AB  - Oncocytic tumours of adrenal gland are rare lesions with approximately twenty
      five cases being documented in literature. A majority of them are nonfunctional
      and benign. We report a case of adrenal oncocytoma in a 44-year-old male, who
      underwent a laparotomy for a large mass in the abdomen, which was located above
      the left kidney. Routine histopathological examination was suggestive of a benign
      tumour with cells resembling oncocytes. However, immunohistochemistry and
      electron microscopy helped to confirm the diagnosis of an adrenocortical
      oncocytoma.

PMID- 16295432
TI  - Fibrosarcoma of penis--a case report.
AB  - Malignant mesenchymal tumours of penis are rare. A rare case of fibrosarcoma of
      penis in 60 year male is presented herewith.

PMID- 16295433
TI  - Aspiration cytology, histology and hormone status in solid and cystic papillary
      tumor of pancreas--report of three cases.
AB  - Solid and cystic papillary tumor of pancreas (SCPT) are rare tumors. Of the well
      described cases 95% have occurred in women of reproductive age, suggesting a role
      of hormonal factors in the pathogenesis of this tumor. Only few studies
      evaluating estrogen and progesterone receptor status have found it to be
      positive. Cytohistocorrelation and immunohistochemistry for estrogen (ER) and
      progesterone (PR) receptors of three such cases are reported here. All three were
      diagnosed by fine needle aspiration cytology (FNAC) and showed cytoplasmic
      positivity for ER and PR receptors. May-Grunwald Giemsa, Papanicolaou and
      hematoxylin and eosin stained slides were evaluated for cytology and
      histopathology. Unstained methanol fixed slides were used for
      immunohistochemistry. The cytoplasmic staining of ER and PR receptors cannot be
      underestimated, as shown by Carbone A et al which represents ERII receptors. This
      study confirms the presence of ER and PR receptors in these tumors and highlights
      the already established cytological features.

PMID- 16295434
TI  - Bone scan in diagnosis of lymphoma with extensive bone marrow necrosis--a case
      report.
AB  - Bone marrow necrosis (BMN) is a relatively uncommon clinicopathologic entity with
      diverse etiology. We describe a case of BMN in a 11 1/2 year old male child with
      an underlying non Hodgkin's lymphoma T-cell type. With the help of 99m Tc-MDP
      (methylene diphosphonate) bone scan we were able to find out the etiologic factor
      in this case.

PMID- 16295435
TI  - Pleomorphic adenoma of the nasal septum--a case report.
AB  - Pleomorphic adenoma which is also called mixed tumour occur in major salivary
      glands like parotid and submandibular glands, and is rare in other sites such as
      the nasal cavity, pharynx, larynx, trachea and lacrimal glands. Here, we discuss
      a case of pleomorphic adenoma of the nasal cavity.

PMID- 16295436
TI  - Follicular dendritic cell tumor of mesentery--a case report.
AB  - Follicular dendritic cell sarcoma also known as dendritic reticulum cell tumor is
      uncommon. It can arise in lymph nodes and extra nodal sites namely tonsils and
      intra abdominal locations. The tumor morphologically mimicks soft tissue sarcomas
      and hence requires immunohistochemical study for correct diagnosis. It pursues an
      indolent protracted course with recurrence and still be compatible with long
      survival. We report a case of follicular dendritic cell tumor of mesentery.

PMID- 16295437
TI  - Mammary hamartoma--a case report.
AB  - Mammary hamartoma is a rare lesion commonly associated with Cowden syndrome. It
      presents clinically as a fibroadenoma. The nonspecific cytological findings makes
      the pre-operative diagnosis of this lesion difficult. Though hamartomas of the
      breast are predominantly benign, co-existent malignancies within them have been
      reported. These lesions also have a tendency to recur; hence a correct diagnosis
      and extensive sampling of hamartoma is essential. We report a case of mammary
      hamartoma with a brief review of literature.

PMID- 16295438
TI  - Eumycetoma due to Madurella grisea--a case report.
AB  - Mycetoma due to Madurella grisea has not been previously reported from Gujarat.
      We report a case in whom identification of the strain was made through the
      structure and texture of grains, morphology in Sabouraud's dextrose agar and
      histopathology.

PMID- 16295439
TI  - Collagenous micronodules in prostatic adenocarcinoma--a case report.
AB  - Collagenous micronodules are a rare but diagnostically valuable feature seen in
      association with prostatic adenocarcinomas. Herein we report a case of
      adenocarcinoma prostate associated with abundant collagenous micronodules.

PMID- 16295440
TI  - Spuriously elevated automated platelet count in severe burns--a report of two
      cases.
AB  - Increasing use of automated analyzers in the hematology laboratory has resulted
      in enhanced accuracy of results. However, operators of automated analyzers and
      the end users utilizing the automated data need to be aware of factitious results
      which might be reported at times by these instruments. Case summaries of two
      patients with severe burns showing spuriously elevated automated platelet count
      are presented here.

PMID- 16295442
TI  - Thymolipoma--a case report.
AB  - A 28 year old male presented with a 8 months history of chest pain, cough and
      breathlessness. CT scan revealed a large mass in right anterior mediastinum
      showing fat and soft tissue attenuation. Histopathology of the resected mass
      revealed a tumour showing extensive areas of mature fat and relatively less
      interspersed thymic tissue confirming thymolipoma. Because of its rarity, we are
      presenting this case with a brief review of literature.

PMID- 16295441
TI  - Schwannomatosis presenting as a painful gluteal swelling--a case report.
AB  - A 58 years old male came with a painful swelling in right gluteal region. On
      examination a small mass was found which was subsequently excised.
      Histopathological study reported presence of presumptive schwannomatosis, as
      there were 4 tumours composed of Antoni A and Antoni B areas along with Verocay
      bodies. As post-operative MRI scan of base of brain and ophthalmological
      examination of patient failed to reveal vestibular schwannomas and ocular
      stigmata of neurofibromatosis type 2 (NF-2) respectively, a final diagnosis of
      definite schwannomatosis was made.

PMID- 16295443
TI  - Juvenile polyposis with macrocephaly and mental retardation (? Ruvalcava-Myhre
      Smith syndrome)--a case report.
AB  - A male child aged one and a half years with a history of rectal bleeding, on
      examination was found to have severe degree of anaemia with grade -III protein
      energy-malnutrition and pneumonia. Colonoscopy revealed features of colonic
      polyposis. An upper gastro-intestinal endoscopy showed a duodenal polyp while
      barium meal follow-through did not reveal any polyps in the small intestine.
      Total colectomy and ileo-rectal anastomosis was done. Following histopathological
      study, the diagnosis of Juvenile polyposis syndrome was made, a very rare entity
      and is known to lead to adenocarcinoma of the gastrointestinal tract. In addition
      the child was found to have macrocephaly and mental retardation. The rarity and
      importance of the diagnosis of juvenile polyposis syndrome associated with
      macrocephaly and mental retardation (?Ruvalcava-Myhre-Smith syndrome) prompted
      the documentation of this case.

PMID- 16295444
TI  - Cytological diagnosis of cholangiocarcinoma with rib metastasis in a young female
      -a case report.
AB  - Intrahepatic cholangiocarcinomas are second most common primary tumors of the
      liver. They are usually seen in 6th to 7th decades of life and at an advanced
      stage leading to poor prognosis. Their occurrence in the young age group is rare.
      Histopathological features of this tumor are well documented but literature
      regarding cytomorphological features on FNA is limited. We describe the
      cytological features of this tumor in a young woman presenting primarily with a
      rib metastasis. FNA smears from hard lump in the right chest wall and liver mass
      showed small round tumor cells arranged in the form of sheets, clusters and
      occasional tubules. The cells showed mild pleomorphism and bland nuclear
      morphology. Intimately admixed with tumor cells were spindle shaped fibroblastic
      cells. Serum alpha-fetoprotein level was within normal limit. Special stain for
      bile and immunocytochemical staining for NSE, chromogranin and CALLA were all
      negative. Cholangiocarcinoma was diagnosed based on cytological findings and
      special stains and this diagnosis was histologically confirmed on biopsy.

PMID- 16295445
TI  - Insular carcinoma of thyroid--a case report.
AB  - Insular carcinoma of thyroid (ICT) is a rare tumor, which accounts for 4-6% of
      thyroid malignancies. ICT arising from follicular cells of thyroid shows a
      characteristic insular growth pattern characterized by solid nests of tumor cells
      separated by vessels. A 52-year-old female presented with a huge swelling in
      midline of the neck with retrosternal extension. The patient was euthyroid. Near
      total thyroidectomy was done. Grossly, the tumour was involving both the lobes
      and isthmus of thyroid. Microscopic examination revealed features of insular
      carcinoma. On immunohistochemistry, tumour cells were positive for thyroglobulin
      and negative for calcitonin.

PMID- 16295446
TI  - Hamartoma of the breast--a case report.
AB  - A 45 year old female presented with a discrete palpable mass in the right breast.
      Repeated fine needle aspiration of the mass yielded only adipose tissue and was
      reported as lipoma - breast. Microscopic features of the resected mass were
      evaluated in conjunction with the clinical and gross pathologic finding and a
      diagnosis of hamartoma was established. The histological concept of hamartoma of
      the breast as described in the literature is reviewed. Here we report this rare
      case of mammary hamartoma with an unusual abundance of adipose tissue Repeated
      yield of only adipose tissue in an aspirate from a discrete palpable breast mass
      should suggest the possibility of a hamartoma.

PMID- 16295447
TI  - Recurrent aggressive angiomyxoma of vagina--a case report.
AB  - Aggressive angiomyxoma is a rare tumour, which presents as a painless expanding
      mass in the vulvo-vaginal region. It usually occurs in 2nd to 3rd decades of
      life. It behaves like a low-grade sarcoma with high propensity for local spread
      and recurrence and can involve vulva, perineum, vagina and urinary bladder. It is
      difficult to differentiate clinically this tumour from other mesenchymal tumours
      occurring in this region. Microscopically it must be differentiated from
      malignant tumours with myxoid change, like liposarcoma and myxoid leiomyosarcoma.
      Hence, histopathologic examination has a central role in diagnosis of this
      tumour. We are presenting a case of young woman, who came with history of
      swelling in vulva and perineum. Imaging studies in the perineal region revealed a
      large pelvic mass. Fine needle aspiration cytology was inconclusive due to scanty
      material. Enucleation of mass was attempted in first surgery but complete
      extirpation could not be performed. The swelling recurred within few weeks after
      surgery and required irradiation. A second surgery, however, was successful in
      complete removal of the tumour.

PMID- 16295448
TI  - Acute fulminant visceral leishmaniasis in children--a report of two cases.
AB  - Kala-azar usually presents in older children and young adults with insidious
      onset of fever, splenomegaly and pancytopenia. Characteristic L.D. bodies in bone
      marrow or splenic aspirates are diagnostic of kala-azar. We report two cases of
      visceral leishmaniasis in children-1 1/2 and 10 year old with unusual
      presentation and fulminant course. In case 1 a female presented with fever,
      jaundice and bleeding manifestations. Peripheral smear revealed L.D. bodies in
      neutrophils as well as monocytes. The liver function tests were deranged. The
      child died within three days due to respiratory arrest. Case 2 was a boy who
      presented with fever and altered sensorium with deranged liver function tests.
      The patient expired within three days due to hepatic encephalopathy. Thus, it is
      important to consider the diagnosis of Kala-azar even when the presenting
      complaints are atypical and institute diagnostic and therapeutic measures early
      to prevent mortality.

PMID- 16295449
TI  - Meckel Gruber Syndrome--a case report.
AB  - Meckel Gruber Syndrome is a rare syndrome inherited as Mendelian autosomal
      recessive condition. The affected infant usually has a large occipital
      encephalocoele associated with renal cysts and sometimes polydactyly. The
      prognosis is poor. The affected child is still born or dies early in infancy. If
      diagnosis is done by prenatal ultrasound examination termination of pregnancy can
      be done.

PMID- 16295450
TI  - Seroprevalence of IgG antibodies to Chlamydia pneumoniae and Helicobacter pylori
      among coronary heart disease patients and normal individuals in South Indian
      population.
AB  - In recent years, the role of infectious agents in the aetiology of
      atherosclerotic disease has come to the forefront. In the present study,
      seroprevalence (IgG) of chlamydia pneumoniae and helicobacter pylori in patients
      with atherosclerotic coronary heart disease was compared to normal healthy
      adults. Out of a total of 117 patients 101 had unstable angina (UA) and 16 had
      chronic stable angina (CSA). C. pneumoniae seropositivity was found in 66% of
      patients with UA and 94% of CSA patients. The corresponding figures for H. pylori
      were 58% and 56% respectively. In comparison, 81% of healthy adults were
      seropositive for C. pneumoniae and 53% for H.pylori. No significant association
      was found between CHD and the infectious agents. However, this study has revealed
      a high infection by C. pneumoniae as well as H.pylori in this part of India.

PMID- 16295451
TI  - Seroprevalence of rubella in pregnant women in Kashmir.
AB  - The present study was conducted to determine the seroprevalence of rubella in
      pregnant women in Kashmir. One thousand nine hundred and eighteen pregnant women
      in age group of 20-35 were divided into two groups. Group I (n=892) consisted of
      women with previous history of repeated abortion (507), single abortion (220),
      intrauterine death (149), stillbirth (14) and premature delivery (2). Group II
      (n=1028) pregnant women with previous normal delivery. A total of 1918 pregnant
      women were screened for rubella IgM antibodies out of which 16.74% were positive.
      In women with bad obstetric history (Group I) 26.12% were positive as compared to
      8.96% in women with no significant obstetric history (Group II). The IgM antibody
      positivity was higher in women with previous history of intrauterine death (IUD)
      58.38% followed by stillbirth 57.14%, premature delivery 50%, abortion 21.8% and
      recurrent abortion 17.55%. The high prevalence of disease in this region demands
      urgent needs for prevention. Moreover antenatal cases should be screened as early
      diagnosis and time intervention will help in proper management of these cases.

PMID- 16295452
TI  - Levels of antibody, free antigen and immune-complexed antigen by ELISA in
      different grades of sputum positive patients of pulmonary tuberculosis.
AB  - The ES-31 (31 kDa protein) antigen was isolated from culture filtrate of
      Mycobacterium tuberculosis H37Ra and was shown to have potential in
      immunodiagnosis of pulmonary tuberculosis. Serum samples from 38 confirmed sputum
      positive pulmonary tuberculosis patients were grouped into AFB+, AFB++, AFB+++
      based on sputum bacillary load. Analysis of tubercular antibody, circulating free
      and immune complexed antigen (CIC-Ag) was done in serum samples by Indirect and
      Sandwich ELISA using ES-31 antigen and affinity purified anti ES-31 antibody
      respectively. The analysis of Geometric mean titre (GMT) of all the three groups
      showed that GMT of tubercular antibody was considerably decreased compared to
      elevated levels of CIC-Ag (Antibody: 1360 to 816 and CIC-Ag: 534 to 1744) from
      low bacillary sample to high bacillary samples, whereas there is no significant
      change in the titre of circulating free antigen. Low levels of detectable
      antibody is observed possibly due to removal of antibody from circulation by
      immune complex formation as confirmed by its elevated levels in sputum AFB+++
      positive patients.

PMID- 16295453
TI  - Changing face of septicaemia and increasing drug resistance in blood isolates.
AB  - In a retrospective study conducted between January, 2000 and December 2000, 7157
      adults and children were studied. Amongst these, 1071 patients had positive blood
      cultures. Of these, 575 (53.6%) cases were community acquired septicaemia and 486
      (46.4%) cases had developed septicaemia of nosocomial origin. Gram negative
      aerobes accounted for 708 (66.1%) isolates. Amongst them, Klebsiella pneumoniae
      predominated (23%), followed by Escherichia coli (14%). Acinetobacter spp.
      emerged as the next common pathogen (9%), followed by Salmonella typhi (5.4%).
      Staphylococcus aureus (9%) and coagulase negative staphylococci (9%) were the
      most common gram positive isolates followed by Enterococcus faecalis (4.7%).
      Antibiotic susceptibility of all these isolates was performed by the modified
      Stokes' method. Both Klebsiella pneumoniae and Escherichia coli showed alarmingly
      high resistance to all groups of antibiotics with 70-80% resistance to
      amoxicillin and cephalexin. Minimum resistance was observed against cefotaxime
      (23%) and ciprofloxacin (12%). Majority of Enterococcus faecalis were multidrug
      resistant. Streptococcus pneumoniae exhibited 26% resistance to penicillin. Thus,
      the study clearly highlights the rising level of drug resistance amongst the
      bacterial isolates from blood and hence the need to update and formulate newer
      drug policies.

PMID- 16295454
TI  - Congenital Leukemia (ALL-L2).

PMID- 16295455
TI  - Elevated level of lipoprotein (A) in rural and urban population of Saurashtra
      region.

PMID- 16295456
TI  - Isolation of rare species Vibrio fluvialis in dental plaque.

PMID- 16295457
TI  - Stromal changes in marrow metastasis.

PMID- 16295458
TI  - Pathogenesis of infective endocarditis.
AB  - The present knowledge of epidemiology, microbiology and pathogenesis of infective
      endocarditis in both native valve and prosthetic valve endocarditis is described.
      An attempt has been made to discuss early events in its pathogenesis. This
      understanding may help in the prevention and management strategies.

PMID- 16295460
TI  - Endoscopic and histological changes in upper gastrointestinal tract of patients
      with chronic renal failure.
AB  - To evaluate the endoscopic and histological changes in upper gastrointestinal
      tract of patients with chronic renal failure 50 patients and 50 controls were
      studied. Upper gastrointestinal endoscopy was done and 2 biopsies each were taken
      from oesophagus, corpus and antrum of the stomach and duodenum. Sections were
      stained with haematoxylin & eosin, Alcian blue--Periodic acid Schiff's (pH 2.5),
      and Loeffler's methylene blue stains. Oesophagus was endoscopically normal in
      most of the patients. Predominant histological finding was chronic oesophagitis
      which was significantly higher in patients than controls (47.1% Vs 26%; p<0.05).
      Significantly higher (p<0.001) number of patients had gastritis, oedema and pale
      mucosa on endoscopic examination of stomach. Predominant histological changes
      were mucosal oedema (82.35%), gastritis (23.5%) and increase in number of bi- and
      multinucleated parietal cells with vacuolation and fragmentation of the cytoplasm
      (29%). Prevalence of H. pylori was less in patients as controls (35.2% Vs 54%; p<
      0.01). Endoscopic examination of duodenum mainly showed duodenitis, pale mucosa,
      oedema and nodularity. Brunner's gland hyperplasia (82.4%), duodenitis (70.6%)
      and gastric metaplasia (29.4%) were the main histological features. H. pylori was
      seen in 5.9% cases of gastric metaplasia in duodenum. Patients with CRF have
      significant upper gastrointestinal tract abnormalities which mainly occur due to
      metabolic changes in response to high urea concentration in gastric juice and are
      not related to H. pylori infection.

PMID- 16295459
TI  - A modified thionin acridine-orange stain for mast cells.
AB  - For in vitro studies in mesentery, toluidine blue and thionin dyes are generally
      used. We have tried thionin and acridine orange stains and found it to be good as
      it showed good colour contrast between mast cells and the background tissue. The
      two dyes were selected to give good colour contrast.

PMID- 16295461
TI  - Antiphospholipid antibodies--our experience.
AB  - Antiphospholipid antibodies (APA) have aroused multispeciality interests. In our
      study of 200 cases worked up for APA, we have used a few simple coagulation tests
      to detect lupus anticoagulant (LA) and ELISA to detect anticardiolipin
      antibodies. The positivity rate for LA among cases with recurrent pregnancy loss
      was 4.16% and for aCL 20.8%. The positivity rate for LA in patients with venous
      thrombosis was 6.2%, in arterial thrombosis was 7.14% and in SLE patients was
      58.3%. In conclusion APAs are to be looked for in cases of recurrent pregnancy
      loss, thrombosis in people < 45 years of age without risk factors and SLE
      patients to assess the thrombotic risk and to decide on anti coagulant therapy
      for further management.

PMID- 16295462
TI  - Mast cell profile in uterine cervix.
AB  - Mast cell profile was studied in 50 neoplastic and 50 non-neoplastic conditions
      of the uterine cervix. The mean number of mast cells decreased to 44.8 in chronic
      cervicitis with ulceration, whereas the highest number of mast cells was observed
      in cervical polyp with a mean of 250. The mean number of mast cells was also
      higher in papillary endocervicitis (102.57) and chronic cervicitis (103.8). Mast
      cells were found in close proximity to the cervical glands and around blood
      vessels in non-neoplastic lesions. Mast cell count in carcinoma of cervix ranged
      from 0 to 210 per 10 HPF with a mean of 48.08. When the invasion by tumour was
      extensive the total count of mast cells was lower when compared to minimal
      invasion. The distribution of mast cells was found to be around the tumour
      deposits. Comparison of mast cell densities in neoplastic and non-neoplastic
      conditions revealed an increase in chronic inflammatory processes, while in
      cancers there was diminution in number or total absence of mast cells. There is
      no conclusive correlation between the age of the patients and the density of mast
      cells. An inverse relationship existed between the mast cell population and
      degree of anaplasia as well as of mitotic figures.

PMID- 16295463
TI  - Human papilloma virus infection in Indian nasopharyngeal carcinomas in relation
      to the histology of tumour.
AB  - Nasopharyngeal carcinoma (NPC) is a rare malignancy world-wide. It shows an
      increasing trend in the southern parts of India. Genetic alterations brought
      about by environmental factors, HPV and EBV are thought to be crucial for NPC
      carcinogenesis. This study reports for the first time the incidence of HPV
      infection in NPC in Southern India. Detection of HPV was carried out in 36 NPC
      and 10 adenoid lesions by immunohistochemical analysis. 38.8% of NPC were
      positive for HPV with higher positivity in WHO Type I and WHO Type II cancers.
      One among 10 adenoid lesions also showed presence of HPV. The patients belonged
      to low socio-economic status and had exposure to either tobacco or alcohol alone
      or in combination or kitchen smoke.

PMID- 16295464
TI  - Diagnosis of malignancy of prostate.
AB  - Minimal or complete lack of symptoms hinders early diagnosis of malignancy of
      prostate leading to undue morbidity and mortality. Therefore early detection is
      imperative, making use of simple and safe technique with least of expense. Five
      hundred consecutive patients, who reported with urinary complaints, were assessed
      by digital rectal examination, transabdominal suprapubic ultrasonography for
      prostatic volume/weight and serum assay of prostate specific antigen (PSA).
      Histopathological examination of prostatic biopsy of all the cases was also done.
      Benign prostatic hyperplasia was found in 83.6% of cases and 16.4% of the cases
      were of adenocarcinoma prostate of varying severity (mild, moderate and severe).
      It was found that volume/weight of gland and PSA levels were very good indicators
      of the probable diagnosis and grade of adenocarcinoma. Statistical tests taking
      various levels of PSA values in account also validated the results.

PMID- 16295465
TI  - Viral infections of renal allografts--an immunohistochemical and ultrastructural
      study.
AB  - Viral infections have been recognized as an integral part of both graft injury
      and rejection. On routine histology, viral infections are diagnosed only when
      fully established, by the presence of viral inclusions or cytopathic effect.
      Although renal transplants are routinely done in many centres in India, the
      incidence of viral infections is largely unkown. This study was aimed at
      detecting 5 viral infections namely, cytomegalovirus (CMV), BK polyoma Virus
      (BKV), Herpes Simplex Virus1 and 2 (HSV1 and 2) and Epstein Barr Virus (EBV) in
      renal biopsies from 321 renal allograft patients, using immunohistochemical and
      electron microscopic studies. Sixty two biopsies were selected from a total of
      414 (belonging to 321 patients) for immunostaining on the basis of features
      suspicious of viral infections in hematoxylin and eosin stained sections.
      Immunostaining confirmed CMV infection in 8 biopsies, BKV infection in 31
      biopsies and HSV1 in only 2 biopsies. HSV2 and EBV were not detected in any
      biopsy. Two biopsies showing CMV immunopositivity and 5 of BKV were further
      processed for electron microscopy, which supported the diagnoses. Thus, the study
      highlights the prevalence of BKV and CMV infections in renal transplant patients
      having graft dysfunction, to be 9.3% and 1.9%, respectively. Besides, only one
      case each was diagnosed as CMV infection and BKV infection in routine
      histopathological reporting, establishing the importance of immunohistochemical
      studies in early diagnosis of these viral infections.

PMID- 16295466
TI  - Relationship of oral cancer with age, sex, site distribution and habits.
AB  - Many studies are carried out regarding age incidence, tobacco smoking and sites
      of oral cancer, but in Gujarat tobacco chewing in form of Gutkha is more common
      than smoking and start during preteen years. Tobacco chewing causing chronic
      inflammation, submucous fibrosis and oral cancer. This study was conducted on 504
      patients to find out if there is increasing incidence of oral cancer in lower age
      group and its relation with sex as well which site was commonly affected. There
      was statistically significant increase in oral cancer in lower age group, and
      anatomically anterior part of oral cavity showed involvement in 61.32% of cases.
      Though males were affected more but female cases were 25%. So tobacco chewing has
      got detrimental effect on oral cavity.

PMID- 16295467
TI  - Chondroblastoma of bone--not a " benign disease": clinico-pathologic observations
      on sixty cases.
AB  - Chondroblastomas (CBL) account for less than 1% of all bone tumors. A 46 year
      review (1955-2000) of bone tumors yielded 60 cases of CBL. This paper reviews
      their histology, radiology, clinical presentation and emphasizes that this
      seemingly benign lesion is capable of aggressive behaviour. Histopathology slides
      and radiographs of sixty patients were studied and clinical details and follow-up
      were obtained. There were 44 males and 16 females, aged between 10 to 30 years.
      Long bones were involved in 81.4% of the cases, tibia being the commonest site.
      Symptoms comprised pain (60%), local swelling (25%) and joint symptoms (5%) or a
      combination of these. Radiologically, an oval sharply demarcated lytic lesion
      predominantly in the epiphysis was noted in 50% of the cases. On microscopy all
      lesions revealed chondroblasts having irregular grooved nuclei and osteoclasts
      with 80% of the tumors showing chondroid differentiation and calcification.
      Treatment comprised curetting (34 cases), wide excision (21 cases), radical
      excision (1 case) and was unknown in 4 cases. Follow-up ranging from 2 to 26
      years was available in 83.3% of the patients; six (10%) had local recurrence (at
      6 months, 8 months, 1 year, 2 years, 3 years and 5 years), two (3.3%) developed
      lung metastasis (synchronous in one and at 18 months in the other) and
      spontaneous malignant transformation occurred in one (1.4%) patient after 9
      years; subsequent to three local recurrences. CBL, though seemingly benign, can
      behave in an aggressive manner. Since there are no reliable histological features
      to predict biologic behaviour, regular long term follow-up is recommended.

PMID- 16295468
TI  - Platelet large cell ratio in the differential diagnosis of abnormal platelet
      counts.
AB  - Platelet volume indices, estimated by automated blood cell analyzers, are useful
      in the diagnosis of various conditions with abnormal platelet counts. Platelet
      count (PLT), Platelet large cell ratio (P-LCR), Platelet distribution width (PDW)
      and mean platelet volume (MPV) were studied in 779 patients with normal platelet
      counts, 74 patients with high platelet counts and 41 cases with low platelet
      counts. P-LCR was significantly decreased in patients with thrombocytosis than in
      normal while it was increased in thrombocytopenia. In patients with high counts,
      P-LCR was significantly decreased in reactive thrombocytosis than neoplastic
      thrombocytosis. P-LCR was increased in destructive thrombocytopenia than those
      with hypoproliferative thrombocytopenia though it was not statistically
      significant. P-LCR was inversely related to platelet count and directly related
      to PDW and MPV. Platelet large cell ratio if properly utilised can be a good aid
      in the differential diagnosis of conditions associated with abnormal platelet
      counts.

PMID- 16295469
TI  - Skin cancers in chronic arsenic toxicity--a study of predictive value of some
      proliferative markers.
AB  - Prolonged exposure to arsenic contaminated water produces various clinical
      features, cutaneous features e.g. melanosis, keratosis and cancers being very
      common. Evaluation of such lesions by proliferative markers can provide useful
      information in regards to the biological behaviour of the lesions. Thus, cases
      with high proliferative status can be ominous sign for development of cancers. We
      studied skin biopsy of 42 cases. These were evaluated with AgNOR score and PCNA
      stain, in addition to H & E examination. Here, invasive cancer cases had mean
      AgNOR score of 3.56, those with severe dysplasia had 3.0, moderate and mild
      dysplasia scored 1.73, benign changes had mean score of 1.35 while normal control
      cases had 1.08. PCNA index in cancers was above 50, that of severe dysplasia 25
      30, mild to moderate dysplasia 1.0-5.0, those with benign changes 0.5 -1.0 and
      normal control had LI of less than 0.5%. PCNA has the advantage of less chance of
      observer error over AgNOR stain.

PMID- 16295470
TI  - Antithrombin III assay using thrombin in disseminated intravascular coagulation
      (DIC), other thromboembolic disorders and hepatic diseases.
AB  - Fifty cases comprising 11 cases of disseminated intravascular coagulation (DIC),
      16 cases of venous thromboses and 23 cases of hepatic diseases were studied for
      AT III levels using clotting assay. Twelve samples were subjected to ATIII
      estimation by the commercially available synthetic chromogenic assay. Twenty age
      and sex matched controls were also analysed to find out the reference value for
      the techniques. Low AT III levels, if present, were correlated with other markers
      of DIC, viz FDP and D-dimer assays. There was a decrease in the AT III levels in
      all the three disease categories with a significant difference between the AT III
      levels of the three disease categories. In DIC, lowest levels were observed which
      correlated well with FDP and D-dimer levels. There was no significant difference
      between the average AT III levels measured by both the clotting and synthetic
      chromogenic assay with the former procedure being relatively inexpensive.

PMID- 16295472
TI  - Pleuropulmonary blastoma--a rare pathology.
AB  - Pleuropulmonary blastoma is a rare and highly aggressive pulmonary malignancy in
      children. The clinical features, radiologic, cytologic, gross and
      histopathological features of one such case in a 9 year old girl is discussed
      along with a short review of literature.

PMID- 16295471
TI  - Preparation of autologous platelet-rich fibrin glue, an effective tissue adhesive
      in the haematology laboratory.

PMID- 16295473
TI  - Metaplastic carcinoma of the breast--a rare breast tumour.
AB  - Malignant breast neoplasms consisting of mixtures of epithelial and mesenchymal
      elements, are a rarity. Pathogenesis of such diverse elements within obviously
      infiltrating carcinomas has been the subject of much controversy. After the
      advent of immunohistochemistry, it is now generally accepted that metaplasia of
      the epithelial elements of a carcinoma gives these lesions their
      pseudosarcomatous appearance. Hence the name metaplastic carcinoma is given to
      malignant breast neoplasms which show Cytokeratin positivity in both epithelial
      and mesenchymal elements. We recently encountered such a case, which is being
      presented here along with relevant review of literature.

PMID- 16295475
TI  - Factor X deficiency--a rare disorder.
AB  - Congenital factor X deficiency is a very rare inherited coagulation disorder. The
      clinical phenotype is of varying bleeding manifestations depending upon the level
      of factor activity. We describe a one and a half year old patient with severe
      deficiency (factor level less than 1%) who manifested with only easy bruisability
      and epistaxis that does not correlate with level of deficiency.

PMID- 16295474
TI  - Fine needle aspiration cytology of extrapancreatic solid-cystic tumour of
      pancreas: a case report.
AB  - Fine needle aspiration cytological features of solid-cystic tumor (SCT) of
      pancreas occurring adjacent to pancreas is reported for its rare occurrence. On
      cytology, diagnosis of paraganglioma was suggested. After histologic diagnosis of
      SCT, cytology was reviewed that showed typical features of SCT. On cytology,
      diagnostic problem in SCT occurring outside pancreas is illustrated.

PMID- 16295476
TI  - Lymphangioma of the fallopian tube--a case report.
AB  - Lymphangioma of the fallopian tube is very rare. Only one such case has been
      reported. A 30-years-old female with lymphangioma of the left fallopian tube is
      described here. She presented with fever, vaginal bleeding and foul smelling
      discharge. A mass was felt in left fornix. On exploratory laparotomy, a left tubo
      ovarian mass adherent to the surrounding structures was seen. Clinical diagnosis
      was septic abortion with adhesions. Left-sided partial tubectomy was performed.
      Histology of the left tube revealed large dilated channels containing lymph in
      the submucosa. Lymphocytes were also seen in some channels. Histogenesis of
      lymphangioma remains uncertain. Presence of adhesions in this case suggests a
      reactive origin. Histopathology is confirmatory for diagnosis.

PMID- 16295477
TI  - Sarcoma-like mural nodule in an ovarian mucinous cystadenoma: a case report.
AB  - Mural nodules are rare lesions seen in the walls of mucinous cystic tumours of
      ovary and are exceptionally rare in other ovarian neoplasms. The histological
      pattern of these mural nodules varies greatly from the mucinous tumours
      themselves. A rare case of a sarcoma like mural nodule is presented here which
      has microscopic resemblance to malignancy but is associated with good clinical
      outcome.

PMID- 16295478
TI  - Fibrosarcoma of breast.

PMID- 16295479
TI  - Angiomyoma of the palate--a case report.
AB  - Leiomyomas are rare tumors of the palate amongst which angiomyomas are the
      commonest sub-type. Recurrence is rare and prognosis is excellent. Only a few
      case reports are available in literature. We report a case of angiomyoma of the
      palate presenting as an encapsulated swelling in the roof of the mouth.

PMID- 16295480
TI  - Primary squamous cell carcinoma of gallbladder presenting as acute cholecystitis.
AB  - Primary squamous cell carcinoma of gallbladder accounts for only 0-12.7% of all
      cases of gallbladder cancer. We here report a case of primary squamous cell
      carcinoma of gallbladder presenting as acute cholecystitis. A 50 year old man was
      admitted with the complaints of pain in right hypochondrium and fever of 2 days
      duration. Abdominal examination revealed tenderness along with guarding and
      rigidity in right hypochondrium with positive Murphy's sign. The patient was
      conservatively treated as a case of acute cholecystitis. After 12 hrs of
      unrewarding treatment patient was operated upon and cholecystectomy done. The
      specimen revealed thick walled gallbladder with multiple calculi. Histopathology
      revealed squamous cell carcinoma grade II.

PMID- 16295481
TI  - Paroxysmal nocturnal hemoglobinuria with onset in childhood: a case report.
AB  - A twelve-year-old boy presented with recurrent episodes of anemia. Complete blood
      counts showed pancytopenia. Bone marrow was hypercellular with erythroid
      hyperplasia and depleted stores of iron. Positive Ham's test and sucrose lysis
      test revealed that he had paroxysmal nocturnal hemoglobinuria. There was a delay
      of nearly two years in the diagnosis in this patient. Paroxysmal nocturnal
      hemoglobinuria is rare in childhood. It must however be considered in a child who
      presents with unexplained anemia or bone marrow failure so that an early and
      accurate diagnosis is reached.

PMID- 16295482
TI  - Plasmacytoid variant of myoepithelioma of palate: a case report.
AB  - Myoepitheliomas of intraoral minor salivary glands are rare and are usually of
      plasmacytoid type. Myoepitheliomas are considered difficult to diagnose without
      the aid of ultrastructural and histochemical studies. Here we present a case
      report of plasmacytoid type of myoepithelioma of palate that was diagnosed by
      light microscopic examination alone. Considering the non-specificity of
      ultrastructural and histochemical findings, it is important to pay attention to
      typical features of plasmacytoid myoepitheliomas to arrive at a diagnosis.

PMID- 16295483
TI  - Primary adenocarcinoma (intestinal type) of nasal septum--a case report.
AB  - Primary nasal septal adenocarcinoma is a rare lesion. A sporadic case of septal
      adenocarcinoma in a 22 years old male is being described along with review of
      literature.

PMID- 16295484
TI  - Primary thyroid lymphoma: a report of two cases.
AB  - Primary thyroid lymphomas (PTLs) are rare neoplasms which in the past have been
      classified by various schemes. Clinicopathological findings of two cases which
      were diagnosed in the past one year in our institute are presented using the
      Revised European and American classification (REAL) for lymphomas. Both cases
      presented as enlarging neck masses in elderly female patients, in association
      with lymphocytic thyroiditis. One case was diagnosed as a MALT (mucosa associated
      lymphoid tissue) lymphoma while the other was a diffuse large cell lymphoma
      (DLCL).

PMID- 16295485
TI  - Adenomyoepithelioma of the breast: a potential diagnostic pitfall on fine needle
      aspiration cytology.
AB  - Adenomyoepithelioma is a rare myoepithelial cell-rich tumour of the breast. We
      report a case of adenomyoepithelioma in a 60-year-old female, where it evoked the
      suspicion of a carcinoma on fine needle aspiration cytology (FNAC) smears and
      also review the literature on FNAC diagnosis of this rare tumour.

PMID- 16295486
TI  - Paget's disease of the nipple diagnosed on cytology: a case report.
AB  - Paget's disease of the breast nipple is an eczematous skin change of the nipple
      areola complex often associated with an underlying in-situ or invasive carcinoma.
      The usefulness of cytology in the diagnosis of Paget's disease has been suggested
      only in few studies despite the fact that it offers definitive advantages over
      surgical excision biopsy. Easy practicability, quick, cost-effective and non
      invasive stands opposite a limited sensitivity as disadvantage. We report a case
      of Paget's disease of nipple diagnosed by nipple touch smears.

PMID- 16295487
TI  - Postmortem pathology of opportunistic infection in a HIV positive patient--a case
      report.
AB  - An autopsy case of HIV positive patient with multiple opportunistic infections is
      described. We received heart, lungs, spleen and both the kidneys along with
      pieces of cerebrum for anatomy and histopathological examination. Histology of
      organs revealed disseminated non-granulomatous necrotizing type of tissue
      reaction with superadded infection with Cryptococcus neoformans (C. neoformans)
      in liver and brain. Pneumocysts carini (P. carini) induced pneumonia in lungs,
      disseminated mycobacterial infection in spleen, lungs, liver and kidneys and
      acute fibrinous meningitis with superadded infection with C. neoformans in brain.
      Special stains were carried out to demonstrate different organisms.

PMID- 16295488
TI  - Spurious automated red cell parameters due to cold agglutinins--a report of two
      cases.
AB  - Although automation in hematology has resulted in improved accuracy of results,
      there are certain clinical conditions in which even the technologically advanced
      cell counters give out spurious results. It is therefore important that operators
      of these instruments are aware of these factitious results and the clues in the
      automated data that can be of help in identifying them. Two cases with spurious
      automated red cell parameters due to cold agglutinins are reported here.

PMID- 16295489
TI  - Pigmented trichoblastoma: report of a rare case.
AB  - Trichoblastoma is a rare benign skin appendage tumour with follicular
      differentiation. Pigmented variant of trichoblastoma is an extremely uncommon
      tumour and only three cases have been described in the literature. We report a
      rare case of pigmented trichoblastoma in a 54-year-old female.

PMID- 16295490
TI  - Pure pulmonary arterial tumour embolism--a rare cause of pulmonary infarction.
AB  - Pulmonary vascular involvement in the natural course of spread of malignant
      tumours can produce respiratory distress and often manifests as lymphangitis
      carcinomatosis or carcinomatous arteriopathy. Pulmonary infarction due to
      arterial tumour embolism is infrequent. This is a report of a treated case of
      cervical cancer in middle-aged woman who presented after three years with
      infarction of the lungs following arterial tumour emboli.

PMID- 16295491
TI  - Primary malignant melanoma of cervix: a case report.
AB  - Primary malignant melanoma of cervix is a rare entity. A case of primary
      malignant melanoma of cervix presented with vaginal discharge and black colored
      growth over cervix. Histology showed malignant pleomorphic cells with melanin
      pigment in the cytoplasm.

PMID- 16295492
TI  - Hereditary coagulation factor X deficiency--a clinico-haematological profile of 5
      cases from Varanasi.
AB  - Hereditary factor X deficiency is one of the rarest inherited coagulation factor
      deficiency. We are presenting here clinico-haematological profile and diagnostic
      approach of five such cases seen by us over a period of eleven years (year 1991
      2001).

PMID- 16295493
TI  - Pancreatoblastoma (infantile pancreatic carcinoma)--a case report.
AB  - Pancreatoblastoma or infantile pancreatic carcinoma is a rare pancreatic tumor
      with distinct acinar and squamoid cell differentiation that generally affects
      infants and young children. Ultrasound and CT scan may be useful but preoperative
      diagnosis is often quite difficult. The outcome is generally favourable. A such
      case of 10 years old boy with an abdominal mass is being presented.

PMID- 16295494
TI  - Fine needle aspiration cytology of chondroblastoma--a case report.
AB  - Chondroblastoma accounts for less than one percent of osseous neoplasms, and is
      one fifth as common as giant cell tumor, a lesion with which it is very
      frequently confused. It has a marked predilection for the epiphysis of long
      bones. Radiologically, these are lytic lesions with a thin margin of increased
      density. A majority of chondroblastomas have an entirely benign course and are
      successfully treated by curettage and bony chip grafts. Clinically,
      chondroblastomas may be confused with other neoplasms, both benign and malignant.
      Fine needle aspiration is fast gaining acceptance as an accurate and rapid
      technique for diagnosing osseous neoplasms. The cytological features of
      chondroblastoma like individually lying chondroblasts, nuclear grooves, chodroid
      matrix and chicken-wire calcification are diagnostic of this neoplasm and may
      allow fine needle aspiration to become a valuable pre-operative technique in the
      management of these patients.

PMID- 16295495
TI  - Acute megakaryoblastic leukaemia: a clinico-haematological profile of five cases.
AB  - Herein we are presenting the clinical, morphological and cytochemical
      characteristics of five cases of acute megakaryoblastic leukaemia (AML-M7) seen
      by us over a period of five years (Jan 1996-Dec 2000). Morphological assessment
      revealed marked polymorphism of blast cells and platelets both in the peripheral
      blood and bone marrow smears in all cases. Size of the blast cells ranged from
      very small to very large multinucleated cells, with variable chromatin pattern
      and number of nucleoli. More differentiated megakaryocytic cells showing
      cytoplasmic blebs, protrusions and platelet budding with bizarre platelet
      morphology were characteristic features suggesting the diagnosis. Cytochemical
      stains like myeloperoxidase, sudan black and PAS were positive in 5-15% of blast
      cell. Coagulation studies revealed a normal coagulation profile, whereas platelet
      studies showed marked impairment in aggregation of platelets with ADP and
      adrenalin with a normal PF-3 availability.

PMID- 16295496
TI  - Apocrine carcinoma of the breast presenting as a solitary cyst: cytological and
      histopathological study of a case.
AB  - Apocrine carcinoma is a rare, unique and morphologically distinct type of
      invasive breast carcinoma. This tumor has predilection for elderly females (6th
      and 7th decade). This report is of apocrine carcinoma of the breast arising in a
      27 year old female, a rare occurrence in this age group, with only a few cases on
      record.

PMID- 16295497
TI  - Follicular cervicitis: a case report.
AB  - Chronic follicular cervicitis (CFC) is a benign inflammatory condition which can
      be easily diagnosed with a fair degree of assurance on pap stained cervical
      smears, thus preventing the need for cervical biopsy. We report a case of CFC in
      a postmenopausal woman.

PMID- 16295498
TI  - Nephrogenic metaplasia of urinary bladder--a case report.
AB  - Nephrogenic metaplasia of urinary bladder, with synonyms of nephrogenic adenoma,
      mesonephric adenoma or adenomatoid tumour is a rare metaplastic lesion which can
      be clinically as well as morphologically mistaken for malignancy of the bladder.
      We present one case because of its rarity and also to emphasize the need for
      increase in its awareness both among urologists and pathologists, leading to
      accurate identification of the lesion.

PMID- 16295499
TI  - Hypoplasia of the abdominal aorta--a case report.
AB  - Infrarenal aortic coarctation is a very uncommon vascular disease. It has been
      named as hypoplasia of abdominal aorta, mid aortic dysplasia, mid aortic
      syndrome, atrophy of aorta, atresia of the terminal aorta & atypical coarctation.
      The pathogenesis is still controversial. Hypertension is an almost universal
      feature of this disorder. We present a case report with postmortem findings of a
      young female patient having hypoplasia of abdominal aorta for its rarity.

PMID- 16295500
TI  - Parotid gland tuberculosis--a case report.
AB  - Isolated parotid gland tuberculosis in the clinical absence of tuberculosis
      elsewhere in the body, is a rare clinical entity. It is often misdiagnosed as
      parotid gland tumour in the absence of symptoms suggestive of tuberculosis. We
      are presenting this case to highlight the unusual solitary nature of the lesion,
      the absence of any other tuberculous focus in the body, the inconclusive findings
      of the pre-operative investigations like fine needle aspiration cytology (FNAC),
      and computed tomography (CT), and the need for histopathology for definitive
      diagnosis.

PMID- 16295501
TI  - Intramuscular myxoma report of a case diagnosed on fine needle aspiration
      cytology.
AB  - Intramuscular myxoma is a relatively rare soft tissue tumour. Here we present a
      case which was diagnosed as intramuscular myxoma on cytology and confirmed on
      histopathology. This is the first such reported case from this country.

PMID- 16295502
TI  - Tissue concentration, systemic distribution and toxicity of clofazimine--an
      autopsy study.
AB  - There are very few autopsy studies available on systemic distribution of
      clofazimine, a drug with anti-mycobacterial activity, used in multidrug therapy
      (MDT) regimen of leprosy and in erythema nodosum leprosum (ENL). An autopsy study
      was done on a 45 year old female of lepromatous leprosy (LL) on MDT and long term
      high dosage of clofazimine. Patient succumbed to intractable abdominal pain,
      diarrhoea, hypokalemia following clofazimine treatment. Autopsy study revealed
      yellowish brown discoloration of skin, viscera and body fluids. Chemical
      extraction of the drug revealed the highest concentration of the drug in jejunum
      (1.5mg/gm),followed by spleen (1.2mg/gm), pancreas (0.4mg/gm), adrenal
      (0.25mg/gm), liver (0.21mg/gm), and less than 0.2mg/gm in lung, fat, large
      intestine and stomach. It can be inferred from the present study that the drug is
      absorbed from the jejunum and gets deposited in fat, reticulo-endothelial cells
      (R-E cells) and hepatocytes. The drug is best demonstrated in cryostat sections
      and is lost partly during tissue processing and staining. The drug toxicity can
      be fatal as seen in the present case.

PMID- 16295503
TI  - Bacteriological and mycological study of corneal ulcers in and around Aurangabad.
AB  - In the present study an attempt was made to find out bacteria and fungi causing
      corneal ulcers. Sixty cases of corneal ulcer were studied. Corneal scrapings from
      patient of corneal ulcer were collected and processed for isolation of bacterial
      and fungal agents. The commonest age group affected was 21-30 yrs. Incidence of
      corneal ulcer was more in males 39 (65%) as compared to females 21 (35%). Trauma
      was the commonest predisposing factor. Out of sixty cases of corneal ulcer
      positive cultures were obtained in 23 (38.33%). Bacteria were isolated in 10
      (16.66%) fungi in 12 (20%) and mixed culture in 1 (1.66%) of the patients. Among
      the bacterial isolates commonest was Staphylococcus aureus 6 (10%). Among fungal
      isolates Fusarium species was the commonest isolate 4 (6.66).

PMID- 16295504
TI  - Dermatophytosis in Khammam (Khammam district, Andhra Pradesh, India).
AB  - Clinically diagnosed 100 cases of dermatophytosis were examined and subjected to
      mycological study. Among them, 45 cases were positive by direct microscopy as
      well as by culture, 11 cases were positive only culture and 14 cases were
      positive by direct microscopic examination. The common clinical presentation was
      Taenia corporis in sixty cases. The commonest species encountered were
      Tricophyton rubrum in 42 cases (60%) and Tricophyton violaceum in 18 cases (26%).
      The prevalence of infection was more in males. Infection was more common in 21-30
      years of age group. The incidence was more during the months of March to July in
      patients who were agricultural labourers living in rural areas.

PMID- 16295505
TI  - Neurocysticercosis in clinically suspected and MRI proven cases: evidence of sub
      optimal antibody response.
AB  - Neurocysticercosis (NCC) has a worldwide distribution mainly in the developing
      countries like India. The study was done to find the seroprevalence of anti
      cysticercus antibodies in clinically suspected and MRI proven cases and to
      corroborate the serological findings with radiological findings (MRI). A hospital
      based study among 204 suspected patients during January, 1996 to August, 2001
      showed that 77 (32.2%, M:F = 2.2:1) had serological evidence of NCC. Of the total
      189 sera, tested at 1:100 dilution 68 (35.9%) and of the total 50 CSF, tested at
      1:5 dilution 9 (18%) were positive for anti-cysticercus IgG antibodies. In 35
      cases where both were tested 13 sera (37.1%), 9 CSF (25.7%) and in 7 (20%) both
      sera and CSF were positive. In CSF from 62 patients with tubercular meningitis
      (disease control) 2 (3.2%) samples whereas in sera of 60 normal blood donors
      (normal control) 7 (11.7%) samples had anti-cysticercus IgG antibodies. In 33 MRI
      positive cases, anti-cysticercus antibodies were seen in 15 (45.4%) patients.
      Antibodies were seen in 6 of 14 (42.8%) cases with single cortical cyst, 4 of 11
      (36.3%) with 2-3 cysts and in 5 of 8 (62.5%) with multiple cysts. Alternatively,
      18 of 33 (54.5%) MRI positive cases lacked anti-cysticercus antibodies. Six MRI
      negative cases were found to be seropositive and were treated successfully.
      Hence, immune response was sub-optimal even in MRI positive cases and conversely,
      few MRI negative cases were seropositive. Since positive response with MRI or
      serology depends on the stage of the disease, therefore both tests should be done
      together to confirm or to rule out NCC.

PMID- 16295506
TI  - Entomophthoromycosis in South Bengal (Eastern India): a 9 years study.
AB  - Subcutaneous mycoses caused by the family Entomophthoraceae is very rare type of
      disease and is being reported sporadically from various Tropical countries
      including India. Here we report 8 cases of rhinoentomophthoromycosis caused by
      Conidiobolous coronatus and 7 cases of chronic subcutaneous phycomycosis caused
      by Basidiobolus ranarum. Cases were detected during a span of 9 years between
      1991 to 1999, from 9 districts in and around Kolkata (Eastern India). Former type
      of lesions were detected among 20 to 65 age group of healthy individuals,
      predominantly males (7:1). In the latter type, male-female ratio was 2:5, and
      except for one all cases belonged to below 20 years age group of healthy
      individuals. Several cases were detected only after examination of repeat biopsy
      samples. With high degree of clinical suspicion, right approach is needed for
      laboratory confirmation of diagnosis.

PMID- 16295507
TI  - Beta2 microglobulin as a surrogate marker for HIV infection: good correlation
      with CD4 counts.
AB  - To determine if beta-2 microglobulin (beta2M) levels were elevated in our HIV
      infected patient population and if it could be used as a surrogate marker for
      disease progression. Thirty-eight HIV infected individuals and 26 age and sex
      matched controls were studied. Measurement of CD4 cell count was carried out on a
      flowcytometer using anti-human CD4 monoclonal antibody and beta2M was measured by
      an enzyme immunoassay. Mean levels of HIV infected individuals were 1.29 +/- 0.52
      mg/L and were significantly higher than 0.74 +/- 0.07 mg/L, the value of controls
      (p value <0.01). There was a negative correlation between CD4 counts and beta2M
      levels (r-value-0.79, p value <0.001). Beta2M levels in HIV infected individuals
      who have no opportunistic infection are elevated and these levels correlate with
      the CD4 counts. Beta2M can be used for the clinical follow-up of patients with
      HIV infection.

PMID- 16295508
TI  - Polymerase chain reaction to detect Chlamydia trachomatis and adenovirus in the
      nasopharyngeal aspirates from paediatric patients with lower respiratory
      infections.
AB  - Polymerase chain reaction (PCR) was evaluated to detect Adenoviruses and
      Chlamydia trachomatis on nasopharyngeal aspirates (NPA) obtained 4-5 days after
      the onset of lower respiratory tract illness in children. Forty-five
      nasopharyngeal aspirates (NPA) from 45 children with lower respiratory tract
      infections were processed for the detection of C. trachomatis and Adenovirus by
      Fluorescent antibody test (FAT), culture and PCR for the cryptic plasmid of C.
      trachomatis and the gene coding for hexon of Adenoviruses. Seven (13.3%) and 4
      (6.6%) of the 45 specimens were positive for C. trachomatis and adenovirus by PCR
      respectively, which included one specimen each positive for these agents.
      Cultures were negative for both the organisms. PCRs showed a statistically
      significant (McNemar test--p= 0.004) higher sensitivity. PCR test is necessary to
      detect C. trachomatis and adenovirus in nasopharyngeal aspirates obtained 4-5
      days after the onset of illness.

PMID- 16295509
TI  - Extrapolation method: as effective as the conventional methods for INR
      determination.

PMID- 16295510
TI  - Amastigote forms of Leishmania donovani in peripheral blood.

PMID- 16295511
TI  - Automated IHC stained slide service available to readers of IJPM.

PMID- 16295512
TI  - Restoring the feeling of sense in healthcare: a diagnosis and therapy.

PMID- 16295514
TI  - Feasibility study of a Latest Date of Delivery (LDD) system of managing
      pregnancy.
AB  - BACKGROUND: This study aimed to establish the acceptability of a Latest Date of
      Delivery (LDD) system of managing pregnancy. An LDD is the date at 42 weeks on
      which labour will be induced if a woman has not delivered by then. This study
      examined whether women under conventional expected date of delivery (EDD)
      management would find an LDD system acceptable in principle, and whether they
      would prefer it to the EDD system. An additional objective was to examine changes
      in state anxiety in late pregnancy, post-term, and after delivery. METHODS: This
      was a preliminary survey of women's attitudes towards an LDD system. Sixty-two
      women under normal pregnancy management completed questionnaires about the
      acceptability of an LDD system at 36 weeks gestation. In addition, questionnaires
      measuring state anxiety were completed at 36, 38, 40, and 41 weeks. RESULTS: The
      majority of women evaluated an LDD system positively, with 64% of women saying
      they would agree to an LDD and only 11.3% saying they would not. Forty percent of
      women said they would prefer an LDD to an EDD system and 36% said they were not
      sure. Women who had not delivered by 41 weeks had significantly more anxiety than
      those who had delivered. CONCLUSIONS: The LDD system appears to be acceptable to
      women and, for 40% of women, preferable to the EDD. Anxiety appears to increase
      as women go post-term, but problems of attrition mean the results regarding
      anxiety should be treated cautiously. Potential difficulties with implementing an
      LDD system are discussed.

PMID- 16295513
TI  - Fear, pain and stress hormones during childbirth.
AB  - AIMS: To investigate the course of fear, pain and stress hormones during labor,
      and the associations between fear, pain, stress hormones and duration of labor in
      nulliparous women with and without epidural analgesia (EDA). METHOD: One day
      during gestation weeks 37-39, urinary and salivary samples were collected to
      measure catecholamines and cortisol. Hourly during labor, the participants
      answered the Delivery Fear Scale and a pain intensity scale, and urinary and
      salivary samples were collected to measure stress hormones. RESULTS: The course
      of fear, pain and stress hormones differed throughout labor in women with and
      without EDA. Pain and cortisol increased throughout labor in women without EDA.
      Women who received EDA had more fear, but not more pain, before the
      administration of the EDA than women who did not receive EDA. Pain, fear and
      catecholamines decreased when women received EDA, but fear and pain increased
      again later in labor. Fear and pain correlated, as well as levels of fear in the
      different phases of labor. During phase one of labor epinephrine and duration of
      the phase were negatively correlated. CONCLUSION: The course of fear, pain and
      concentrations of stress hormones differed, highly influenced by the
      administration of EDA. Fear and pain correlated more pronounced than stress
      hormones and fear, pain and duration of labor.

PMID- 16295515
TI  - Depressive symptoms and psychosocial stress across the transition to parenthood:
      associations with parental psychopathology and child difficulty.
AB  - The transition to parenthood is often accompanied by depression and stress.
      Several studies have established risk factors for postpartum depression, e.g.,
      antenatal depression. However, only a few studies have involved fathers.
      Moreover, most studies focus on the prevalence of depression instead of
      intraindividual changes over time. Our study investigated differential effects of
      parental psychopathology and child difficulty on the course of depressive
      symptoms and feelings of stress for first-time mothers and fathers. Seventy-four
      mothers and 58 fathers completed questionnaires on depressive symptoms (EPDS) and
      feelings of stress during pregnancy, and at 1, 3, 12, and 18 months postpartum.
      Parents rated children's difficulty-fussiness at 3, 12, and 18 months postpartum
      (ICQ). Parental psychopathology was established during pregnancy using self
      reports (SCL-90-R) and anamnestic data. In mentally healthy mothers and fathers
      depressive symptoms decreased from pregnancy to 18 months postpartum, whereas
      parents with psychopathology in pregnancy showed a tendency to prolonged
      depressive phases. In parents with psychopathology, feelings of stress peaked at
      12 months postpartum. Child difficulty was associated with elevated levels of
      psychosocial stress, but only for some participants. Parental psychopathological
      symptoms during pregnancy should thus be considered as a risk factor for elevated
      and prolonged depression and elevated psychosocial stress in mothers and fathers
      across the transition to parenthood.

PMID- 16295516
TI  - The prevention of postnatal depression: a narrative systematic review.
AB  - This systematic review assessed the success of randomized controlled trials of
      preventative interventions for postnatal depression (PND). Outcomes examined were
      estimates of PND prevalence. Methodological quality was determined through the
      examination of key components individually with independent data extraction by
      all three authors. Data sources included Medline, PsycINFO, Sociofile, CINAHL,
      COPAC, EMBASE, Cochrane library; hand searches and a newsletter requests for
      unpublished trials to the Marce Society and Postpartum Support International.
      Twenty-one RCTs were included in this review. Nine of these trials demonstrated
      short-term preventative success (seven psychological and supportive
      interventions, one unpublished antidepressant trial and a calcium carbonate
      trial) but none provided any evidence of long-term success. Furthermore, the
      results of three of the psychological intervention trials should be viewed with
      caution due to a lack of methodological rigour. There is a need for future
      research into the prevention of PND to be tightly designed and maybe include an
      exploration of the experience of postnatal depression for multiparous women.

PMID- 16295517
TI  - Depression, anxiety, hostility and hysterectomy.
AB  - Sixty-five women (aged 32 - 54 yrs) were assessed at 2 months before to 8 months
      after total abdominal hysterectomy on four separate occasions. Beck's Depression
      Inventory (BDI), Taylor's Manifest Anxiety Scale (TMAS), the Buss-Durkee
      Hostility Inventory (BDHI), Measurement of Masculinity-Femininity (MF), Likert
      scales and semantic differentials for psychological, somatic and sexual factors
      varied as assessment tools. High-dysphoric and low-dysphoric women were compared
      with regard to hysterectomy outcomes. Married nulliparae suffered from enhanced
      depression post-surgery. Pre-surgery anxiety, back pain and lack of dyspareunia
      contributed to post-surgery anxiety. Pre-surgery anxiety was related to life
      crises. Pre- and post-surgery hostility occurred in conjunction with poor sexual
      gratification. Post-hysterectomy health improved, but quality of sexual
      relationship was impaired. Partner support and knowledge counteracted
      hysterectomy aftermath. Post-hysterectomy symptoms constituted a continuum to pre
      surgery signs of depression, anxiety or hostility.

PMID- 16295518
TI  - Women's opinion on the use and offer of ovarian reserve testing: a first step
      towards a wide ranged social discussion.
AB  - OBJECTIVE: To determine the opinion among three groups of women (sub-fertile
      women, fertile women and female medical students), concerning the use of ovarian
      reserve tests to determine the chance of an assisted reproductive techniques'
      (ART) induced pregnancy or a spontaneous pregnancy. DESIGN: Prospective study
      using questionnaires in three groups of women: patients visiting the out patient
      infertility clinic at the Academic Medical Centre Groningen, women who had
      delivered at least two children and female medical students. RESULTS: The
      response rate varied from 63% (female medical students) to 56% (fertile women
      with children) and 48% (sub-fertile women). The greater part of women of all
      three groups found it was up to the women themselves to decide whether or not to
      start fertility treatment, even though the ovarian reserve test indicated little
      chance of success. 71% of the sub-fertile women stated that any chance justified
      fertility treatment. None of the three groups of women were very enthusiastic
      about the use of these tests for family planning. CONCLUSIONS: Based on results
      of ovarian reserve tests women could decide not to partake of a - generally
      demanding - fertility treatment. The outcome of the study, however, does not
      support this: even low chances of success are found acceptable. The ability to
      determine the individual ovarian reserve makes this test also a suitable device
      for family planning. The discussion whether these new possibilities will be
      useful for reproductive science will greatly depend on women's attitude towards
      this issue.

PMID- 16295519
TI  - Usefulness of amenorrhoea in the diagnoses of eating disorder patients.
AB  - We investigated the usefulness of amenorrhoea as a criterion in eating disorder
      diagnoses. Menstrual history, eating disordered behavior and weight history of
      251 female eating disorder inpatients were assessed on admission to hospital.
      Menstrual status of 88 (35%) could not be assessed (80 taking hormonal
      contraception, 5 (< 16 years) had never menstruated, one hysterectomized, 2
      postmenopausal). Of the remaining 163; 90 had secondary amenorrhoea (no periods
      for > 3 months), 19 irregular periods and 54 regular cycles. Some patients with
      recent changes in energy status, who warranted inpatient treatment for their
      eating disorder did not develop amenorrhoea until later during their admission.
      Menstrual disturbance is not limited to anorexia nervosa, 24% of patients with an
      eating disorder not otherwise specified (EDNOS) and 15% of bulimic patients had
      amenorrhoea/oligomenorrhoea on admission. The best predictors (82% cases, 83%
      noncases, R2 = 0.41) of secondary amenorrhoea at admission, were; current BMI <
      or = 18, and having rules for exercising. Menstrual status of women with an
      eating disorder diagnosis cannot always be assessed, is mostly measuring low body
      weight and exercise and is not useful in planning or initiating treatment. There
      is insufficient evidence to support the use of amenorrhoea as a criterion for any
      eating disorder.

PMID- 16295520
TI  - On sexual behavior and sex-role reversal.
AB  - Sex is not about reproduction; sex is about (re-)combination of DNA. Sex, not
      reproduction, always involves physical contact between two individuals; to
      achieve this, strategies of sexual behavior evolved. Sexual behavior, therefore,
      did not evolve as part of a reproductive strategy, but evolved to enable exchange
      of genetic material. In multicellular organisms the situation is more complicated
      than in unicellular organisms, as it is impossible for each cell within a
      multicellular body to have sex with another cell. Hence, evolution selected a
      system in which the possibility to have sex was limited to only one cell-line:
      the germ cells. As a result, sex adopted the character of fertilization, and sex
      and reproduction became inseparably linked. Still, in some species, including
      humans, sexual behavior still exhibits features of its evolutionary past: in
      humans (like in bonobo's) most sexual activity and many sexual behavioral
      patterns have nothing to do with reproduction (masturbation, homosexual behavior,
      for example); in humans, sexual behavior also became associated with other
      strategic objectives, such as intensifying the pair bond, expression of love or
      power. Different genders - male and female - evolved, and each gender evolved
      typical gender-related sexual and reproductive strategies as well. In most
      multicellular species, these strategies became inextricably mixed, and sexual
      behavior increasingly more - and in most species even exclusively - 'served' the
      interests of reproduction: sexual behavior became more or less synonymous with
      reproductive behavior. In most species, the 'mix' of sexual and reproductive
      strategies evolved into typical gender-related patterns of behavior, that is, in
      typical 'sex-roles'. Often, males are bigger and more 'beautiful' (= more
      intensely ornamented) than females; males compete with each other for access to
      females; males court females, while females choose males ('female choice').
      However, ecological circumstances may cause a reversal of sex-roles, resulting in
      a situation in which females are bigger and more intensely ornamented than males,
      females compete for access to males, females court males and only males invest in
      care for the young, provided they are relatively certain of their paternity.
      Also, as in the case of the spotted hyena, females may be highly virilized and be
      socially dominant. This 'sex-role reversal' is seen, e.g., when males are
      relatively rare due to high predation pressure, or when the process of
      reproduction is very risky for the same reason: then it is 'better' that males,
      with their plenty of sperm, are wasted, than females with their few, precious
      eggs. It can be argued, with women being the fair sex, exhibiting competitive
      behavior and with an actively displaying courtship, and with men investing
      heavily in their offspring, meanwhile taking all (cultural) kinds of measures to
      guarantee their paternity, that humans, too, exhibit some degree of sex-role
      reversal.

PMID- 16295521
TI  - New therapeutic strategies for systemic sclerosis--a critical analysis of the
      literature.
AB  - Systemic sclerosis (SSc) is a multi-system disease characterized by skin fibrosis
      and visceral disease. Therapy is organ and pathogenesis targeted. In this review,
      we describe novel strategies in the treatment of SSc. Utilizing the MEDLINE and
      the COCHRANE REGISTRY, we identified open trials, controlled trials, for
      treatment of SSc from 1999 to April 2005. We used the terms scleroderma, systemic
      sclerosis, Raynaud's phenomenon, pulmonary hypertension, methotrexate,
      cyclosporin, tacrolimus, relaxin, low-dose penicillamine, IVIg, calcium channel
      blockers, losartan, prazocin, iloprost, N-acetylcysteine, bosentan,
      cyclophosphamide, lung transplantation, ACE inhibitors, anti-thymocyte globulin,
      and stem cell transplantation. Anecdotal reports were omitted. Methotrexate,
      cyclosporin, tacrolimus, relaxin, low-dose penicillamine, and IVIg may be
      beneficial in improving the skin tightness in SSc. Calcium channel blockers, the
      angiotensin II receptor type 1 antagonist losartan, prazocin, the prostacyclin
      analogue iloprost, N-acetylcysteine and the dual endothelin-receptor antagonist
      bosentan may be beneficial for Raynaud's phenomenon. Epoprostenol and bosentan
      are approved for therapy of pulmonary hypertension (PAH). Other options under
      investigation include intravenous or aerolized iloprost. Cyclophosphamide (CYC)
      pulse therapy is effective in suppressing active alveolitis. Stem cell and lung
      transplantation is a viable option for carefully selected patients. Renal crisis
      can be effectively managed when hypertension is aggressively controlled with
      angiotensin converting enzyme (ACE) inhibitors. Patients should continue taking
      ACE inhibitors even after beginning dialysis in hope of discontinuing dialysis.
      Antithymocyte globulin and mycophenolate mofetil appear safe in SSc. The
      improvement in skin score and the apparent stability of systemic disease during
      the treatment period suggest that controlled studies of these agents are
      justified. Stem cell transplantation is under investigation for severe disease.
      Novel therapies are currently being tested in the treatment of SSc and have the
      potential of modifying the disease process and overall clinical outcome. The
      evaluation of these studies is still a difficult process.

PMID- 16295522
TI  - Antiphospholipid antibodies bind ATP: a putative mechanism for the pathogenesis
      of neuronal dysfunction.
AB  - Antiphospholipid antibodies (aPL) generated in experimental animals cross-react
      with ATP. We therefore examined the possibility that aPL IgG from human subjects
      bind to ATP by affinity column and an enzyme linked immunosorbent assay (ELISA).
      Sera with high levels of aPL IgG were collected from 12 patients with the
      antiphospholipid syndrome (APS). IgG fractions from 10 of 12 APS patients
      contained aPL that could be affinity-bound to an ATP column and completely eluted
      with NaCl 0.5 M. A significant (> 50%) inhibition of aPL IgG binding by ATP 5 mM
      was found in the majority. Similar inhibition was obtained with ADP but not with
      AMP or cAMP. All the affinity purified anti-ATP antibodies also bound beta2
      glycoprotein-I (beta2-GPI, also known as apolipoprotein H) suggesting that,
      similar to most pathogenic aPL, their binding depends on this serum cofactor. We
      further investigated this possibility and found that the binding of beta2-GPI to
      the ATP column was similar to that of aPL IgG in that most was reversed by NaCl
      0.5 M. Furthermore, addition of beta2-GPI to aPL IgG significantly increased the
      amount of aPL binding to an ATP column. We conclude that aPL IgG bind ATP,
      probably through beta32-GPI. This binding could interfere with the normal
      extracellular function of ATP and similar neurotransmitters.

PMID- 16295524
TI  - Application of a static fluorescence-based cytometer (the CellScan) in basic
      cytometric studies, clinical pharmacology, oncology and clinical immunology.
AB  - The CellScan apparatus is a laser scanning cytometer enabling repetitive
      fluorescence intensity (FI) and polarization (FP) measurements in living cells,
      as a means of monitoring lymphocyte activation. The CellScan may serve as a tool
      for diagnosis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)
      as well as other autoimmune diseases by monitoring FP changes in peripheral blood
      lymphocytes (PBLs) following exposure to autoantigenic stimuli. Changes in FI and
      FP in atherosclerotic patients' PBLs following exposure to various stimuli have
      established the role of the immune system in atherosclerotic disease. The
      CellScan has been evaluated as a diagnostic tool for drug-allergy, based on FP
      reduction in PBLs following incubation with allergenic drugs. FI and FP changes
      in cancer cells have been found to be well correlated with the cytotoxic effect
      of anti-neoplastic drugs. In conclusion, the CellScan has a variety of
      applications in cell biology, immunology, cancer research and clinical
      pharmacology.

PMID- 16295523
TI  - Insulin as a primary autoantigen for type 1A diabetes.
AB  - Type 1A diabetes mellitus is caused by specific and progressive autoimmune
      destruction of the beta cells in the islets of Langerhans whereas the other cell
      types in the islet (alpha, delta, and PP) are spared. The autoantigens of Type 1A
      diabetes may be divided into subgroups based on their tissue distributions: Beta
      cell-specific antigens like insulin, insulin derivatives, and IGRP (Islet
      specific Glucose-6-phosphatase catalytic subunit Related Peptide); neurendocrine
      antigens such as carboxypeptidase H, insulinoma-associated antigen (IA-2),
      glutamic acid decarboxylase (GAD65), and carboxypeptidase E; and those expressed
      ubiquitously like heat shock protein 60 (a putative autoantigen for type 1
      diabetes). This review will focus specifically on insulin as a primary
      autoantigen, an essential target for disease, in type 1A diabetes mellitus. In
      particular, immunization with insulin peptide B:9-23 can be used to induce
      insulin autoantibodies and diabetes in animal models or used to prevent diabetes.
      Genetic manipulation of the insulin 1 and 2 genes reciprocally alters development
      of diabetes in the NOD mouse, and insulin gene polymorphisms are important
      determinants of childhood diabetes. We are pursuing the hypothesis that insulin
      is a primary autoantigen for type 1 diabetes, and thus the pathogenesis of the
      disease relates to specific recognition of one or more peptides.

PMID- 16295525
TI  - The diagnostic utility of anti-cyclic citrullinated peptide antibodies, matrix
      metalloproteinase-3, rheumatoid factor, erythrocyte sedimentation rate, and C
      reactive protein in patients with erosive and non-erosive rheumatoid arthritis.
AB  - OBJECTIVE: To compare the diagnostic utility of laboratory variables, including
      matrix metalloproteinase-3 (MMP-3), anticyclic citrullinated peptide (CCP)
      antibodies, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C
      reactive protein (CRP) in patients with erosive and non-erosive rheumatoid
      arthritis (RA). METHODS: We assembled a training set, consisting of 60 patients
      with RA, all fulfilling the revised criteria of the American College of
      Rheumatology. A commercial enzyme linked immunosorbent assay (ELISA) was used
      both to test for anti-CCP antibodies (second generation ELISA kit) and MMP; RF
      were detected by latex-enhanced immunonephelometric assay. CRP was measured by
      latex turbidimetric immunoassay. RESULTS: The levels of anti-CCP antibody titers
      and ESR were significantly higher in patients with erosive disease than those in
      non-erosive RA patients (p < 0.001 and 0.0341) respectively. Moreover, a higher
      frequency of elevated titers of anti-CCP antibodies was found in RA patients with
      erosions compared to patients with non-erosive RA (78.3% vs. 43.2% respectively).
      The ROC curves of anti-CCP passed closer to the upper left corner than those
      other markers and area under the curve (AUC) of anti-CCP was significantly larger
      than AUC of other markers (0.755 for anti-CCP, 0.660 for ESR, 0.611 for CRP,
      0.577 for RF, and 0.484 for MMP-3 female). A positive predictive value was higher
      for anti-CCP antibodies in comparison to other markers. We did not find
      significant statistical correlation between anti-CCP antibody titers and
      inflammatory markers such as ESR or CRP. However, we confirmed the correlation of
      elevated titers of anti-CCP antibodies and RF in both groups of patients whereas
      the degree of correlation was more significant in non-erosive patients.
      CONCLUSION: The results of our study suggest that the presence of elevated anti
      CCP antibody titers have better diagnostic performance than MMP-3, RF, CRP and
      ESR in patients with erosive RA.

PMID- 16295527
TI  - The development of mouse APECED models provides new insight into the role of AIRE
      in immune regulation.
AB  - Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy is a rare
      recessive autoimmune disorder caused by a defect in a single gene called AIRE
      (autoimmune regulator). Characteristics of this disease include a variable
      combination of autoimmune endocrine tissue destruction, mucocutaneous candidiasis
      and ectodermal dystrophies. The development of Aire-knockout mice has provided an
      invaluable model for the study of this disease. The aim of this review is to
      briefly highlight the strides made in APECED research using these transgenic
      murine models, with a focus on known roles of Aire in autoimmunity. The findings
      thus far are compelling and prompt additional areas of study which are discussed.

PMID- 16295526
TI  - Unique gene expression patterns in human T-cell lines generated from multiple
      sclerosis patients by stimulation with a synthetic MOG peptide.
AB  - Multiple sclerosis (MS) is an autoimmune disease where T-cells activated against
      myelin antigens are involved in myelin destruction. Yet, healthy subjects also
      harbor T-cells responsive to myelin antigens, suggesting that MS patient-derived
      autoimmune T-cells might bear functional differences from T-cells derived from
      healthy individuals. We addressed this issue by analyzing gene expression
      patterns of myelin oligodendrocytic glycoprotein (MOG) responsive T-cell lines
      generated from MS patients and healthy subjects. We identified 150 transcripts
      that were differentially expressed between MS patients and healthy controls. The
      most informative 43 genes exhibited > 1.5-fold change in expression level.
      Eighteen genes were upregulated including BCL2, lifeguard, IGFBP3 and VEGF.
      Twenty five genes were down-regulated, including apoptotic activators like TNF
      and heat shock protein genes. This gene expression pattern was unique to MOG
      specific T-cell lines and was not expressed in T-cell lines reactive to tetanus
      toxin (TTX). Our results indicate that activation in MS that promotes T-cell
      survival and expansion, has its own state and that the unique gene expression
      pattern that characterize autoreactive T-cells in MS represent a constellation of
      factors in which the chronicity, timing and accumulation of damage make the
      difference between health and disease.

PMID- 16295528
TI  - A study of molecular mimicry and immunological cross-reactivity between hepatitis
      B surface antigen and myelin mimics.
AB  - On the basis of the reported association between hepatitis B vaccination (HBvacc)
      and autoimmune demyelinating complications such as multiple sclerosis (MS), we
      have looked for aminoacid similarities between the small hepatitis B virus
      surface antigen (SHBsAg), and the MS-autoantigens myelin basic protein (MBP) and
      myelin oligodendrocyte glycoprotein (MOG) that could serve as targets of
      immunological cross-reactivity. Twenty-mer peptides spanning 4 SHBsAg/MOG and 1
      SHBsAg/MBP mimicking pairs, were constructed and tested by ELISA as targets of
      cross-reactive responses. A total of 147 samples from 58 adults were collected
      before HBvacc (58/58), and post-HBvacc (48/58 before the second and 41/58 before
      the third boost). Eighty-seven sera from anti-SHBsAg antibody negative patients
      with various diseases were tested as pathological controls. Reactivity to at
      least one of the SHBsAg peptides was found in 8 (14%) pre-HBvacc subjects;
      amongst the remaining 50, reactivity to at least one of the SHBsAg peptides
      appeared in 47 (94%) post-HBvacc. Reactivity to at least one of the MOG mimics
      was present in 4 (8%) pre-HBvacc and in 30 (60%) post-HBvacc (p < 0.001). Overall
      30/50 (60%) vaccinees had SHBsAg/MOG double reactivity on at least one occasion
      compared to none before-vaccination and in 2 (2%) of the pathological controls (p
      < 0.001 for both). SHBsAg/MOG double reactivity was cross-reactive as confirmed
      by inhibition studies. At 6 months post-vaccination, 3 of the 4 anti-MOG reactive
      cases before vaccination and 7 of the 24 (29%) of the anti-MOG reactive cases at
      3 months post-vaccination had lost their reactivity to MOG5-24. There was no
      reactivity to the SHBsAg/MBP mimics. None of the vaccinees reported symptoms of
      demyelinating disorders. In view of the observed SHBsAg/MOG cross-reactivity, the
      vaccine's possible role as an immunomodulator of viral/self cross-reactivity must
      be further investigated.

PMID- 16295529
TI  - Defects in regulation of local immune responses resulting in atherosclerosis.
AB  - Atherosclerosis is nowadays generally accepted as an inflammatory disease but the
      mechanism of its origin and development have not yet been fully clarified. The
      present review focuses on the role of the local immune system as one of the key
      players in the pathogenesis of the complex process. Its part represented by
      vascular-associated lymphoid tissue (VALT) within the arterial wall participates
      directly in the vascular wall's homeostatis. Its inordinate activation during
      ontogenic development of an individual, this formerly defensive and physiologic
      mechanism transform into a pathological process resulting in an impairing
      inflammation. Hsp60, CRP and oxidized or otherwise modified LDL are serious
      candidates for triggering these pathological changes. The principal role is
      played by anti-Hsp60 antibodies and by shear stress originating on the surface of
      endothelium due to blood flow. The experimental and clinical data supporting this
      immunological hypothesis of atherosclerosis are discussed.

PMID- 16295530
TI  - Postinjury malaria: experiences of doctors in Battambang Province, Cambodia.
AB  - Quantitative studies indicate that one-third of trauma victims in malaria endemic
      areas of Cambodia develop postinjury malaria. The main aim of this study was to
      assess the medical significance of the complication. All local doctors with
      trauma care surgical experience in the Battambang Province of Cambodia were
      interviewed regarding their experiences with postinjury malaria (n = 18). The
      qualitative data were processed according to the Editing Style Analysis method.
      In the study area, postinjury malaria has been a well-known complication to
      trauma doctors for years. Local doctors claim that the complication is more
      common in severe as compared to moderate trauma. The complication is reported to
      adversely affect the general condition of trauma patients, increasing the risk of
      wound infections, and delaying postoperative recovery. It was found that the
      informants draw exclusively on personal clinical experience regarding this
      clinical knowledge, asserting that postinjury malaria is not taught at local
      medical schools. The study indicated that post-injury malaria is a significant
      complication to trauma where falciparum malaria is endemic. The knowledge of
      postinjury malaria in the study area seemed to be non-institutional; the
      informants' assessments were exclusively based on their personal clinical
      experience.

PMID- 16295531
TI  - Anemia, malaria and hookworm infections in a Vietnamese ethnic minority.
AB  - The aim of this study was to determine the prevalence of anemia and evaluate the
      relationship of malaria and helminth infections on anemia status in Phan Tien
      village, a mountainous ethnic minority community in southern Vietnam. This
      longitudinal study was performed from April 1997 to 2000 by measuring the
      hemoglobin concentration of 2,767 people who participated in six annual surveys
      at the end of the rainy seasons. Ferritin concentration was measured in 2000 to
      evaluate the proportion of iron deficiency anemia. The relation between malaria
      and intestinal helminth infections with anemia was investigated. Anemia was
      always over 43% and mainly associated with iron deficiency (80.1%). Using
      generalized estimating equations, a small but significant decline of the anemia
      prevalence was detected (OR: 0.805; p < 0.0001). Malaria was significantly
      associated with anemia (OR: 2.408; p = 0.0006). There was no significant effect
      of the control of intestinal helminth infections on the time course of anemia
      (95% CI: -0.1548 to 0.1651).

PMID- 16295532
TI  - Surveillance of imported bancroftian filariasis after two-year multiple-dose
      diethylcarbamazine treatment.
AB  - Myanmar migrants are at increased risk for nocturnally periodic Wuchereria
      bancrofti causing imported bancroftian filariasis. They have a significant
      influence on the effectiveness of diethylcarbamazine (DEC) mass treatment at the
      provincial level in the National Program to Eliminate Lymphatic Filariasis (PELF)
      during the fiscal years (FY) 2002-2006, in Thailand. Two oral doses of DEC 6
      mg/kg are given twice a year to the eligible Myanmar migrants (> or = 2 years
      old). A 300 mg DEC provocation test is given once a year to all Myanmar migrants
      with work permits. Effectiveness evaluation parameters, such as cumulative index
      (CI) and the effectiveness ratio (ER), were obtained after 2 years of the
      multiple-dose DEC treatment program in Ranong Province, Southern Thailand. By
      cross-sectional night blood surveys at the end of FY 2003 in two districts of
      Ranong Province, the microfilarial positive rates (MPR) were 0.8% and 1.2% for
      Mueang Ranong and Kra Buri, respectively. The MPR in the agricultural (1.5%) and
      industrial (0.4%) occupations were not significantly different from each other.
      Our findings suggest that most untreated microfilaremics working in agriculture,
      with short-term residency in Thailand, may have delayed multiple-dose DEC
      treatment.

PMID- 16295533
TI  - Short-term effects of treatment with 300 mg oral-dose diethylcarbamazine on
      nocturnally periodic Wuchereria bancrofti microfilaremia and antigenemia.
AB  - Seven microfilaremic Myanmar patients were treated with a single 300 mg dose of
      diethylcarbamazine (DEC) orally, as part of a case-finding survey in Ranong
      Province, Southern Thailand. This was conducted in order to evaluate the short
      term effects of single-dose DEC on Wuchereria bancrofti microfilaremia and
      antigenemia during a 12-week course of treatment. Analysis of microfilarial
      periodicity on initial treatment revealed the microfilarial peak density (k) was
      at 52 minutes after midnight (0052). The periodicity index was then 103.26%.
      Single-dose DEC treatment did not affect the k values. A linear model of W.
      bancrofti microfilarial density reduction predicts a sharp decrease in the mean
      microfilarial density 2 weeks after DEC intake (Z = -2.197, p = 0.028). Over a
      longer period, a non-linear model predicts an increase in the mean microfilarial
      density to pre-treatment levels, having little or no macrofilaricidal effects. We
      reconfirmed the existence of nocturnally periodic W. bancrofti infection in
      Myanmar migrants in Ranong Province, and the short-term microfilaricidal activity
      of 300 mg single-dose DEC treatment used for biannual mass treatment and the DEC
      provocative test. Without an adequate DEC treatment dose, recrudescence can
      occur. A rational approach to the management of introduced nocturnally periodic
      W. bancrofti in Myanmar migrants, who came for short periods of stay in
      transmission-prone areas, is needed.

PMID- 16295534
TI  - Detection of opportunistic and non-opportunistic intestinal parasites and liver
      flukes in HIV-positive and HIV-negative subjects.
AB  - We assessed the frequency and distribution of infection with opportunistic and
      non-opportunistic intestinal parasites and the liver fluke, Opisthorchis
      viverrini, in HIV-seropositive and HIV-seronegative subjects. Age- and sex
      matched HIV-seropositive (n = 78) and HIV-seronegative patients (n = 78) from two
      hospitals in Khon Kaen Province, Thailand, participated in this study from
      November 1998 to August 2000. These subjects were divided according to the
      presence of diarrhea and CD4 counts. A single stool sample was obtained and
      analyzed by using specific techniques. Opisthorchis viverrini, was the most
      common parasite (19.2%) in each group. The prevalence rates of Cryptosporidium
      spp (11.5%) and Strongyloides stercoralis (17.9%) in the HIV-seropositive group
      were significantly (p < 0.05) higher than those in the HIV-seronegative group
      (1.0% for Cryptosporidium spp and 7.7% for S. stercoralis infections). The
      prevalences of these two parasites were 28% for Cryptosporidium spp and 20% for
      S. stercoralis in HIV-seropositives with diarrhea and CD4 counts lower than 100
      cells/mm3, and were higher compared with patients without diarrhea or with high
      CD4 counts. These results suggest that infection with these parasites increases
      during HIV infection. The epidemiological distribution of Cryptosporidium and S.
      stercoralis may have implications for AIDS-related diseases.

PMID- 16295535
TI  - Therapeutic effect of subcurative dose praziquantel on Schistosoma mansoni
      infected mice and resistance to challenge infection after treatment.
AB  - The therapeutic effect of a subcurative dosage of praziquantel (PZQ) on
      Schistosoma mansoni infected mice and resistance to challenged worm infection
      after treatment were assessed and compared with conventional treatment using a
      curative dosage of PZQ. S. mansoni infected mice were treated with PZQ at a
      curative dosage (600 mg kg(-1)) or a subcurative dosage (300 mg kg(-1)) at 9
      weeks after infection. Untreated mice and non-infected mice were added as
      controls. The therapeutic effect of the drug was evaluated in terms of the
      mortality of mice after treatment, and the parasitological and pathological
      findings in mice sacrificed at 1 week, 1 month, or 3 months after treatment.
      Another sample of mice was not killed but challenged with S. mansoni cercariae at
      1 week, 1 month, or 3 months after treatment. Resistance to re-infection was
      evaluated by the extent of challenged worm reduction. In conclusion, there was no
      significant difference in mortality, or parasitological and pathological findings
      between mice treated with PZQ at the two dosages. However, resistance to
      challenged worm infection was more sustained in the group treated with
      subcurative dose PZQ, especially at 3 months after treatment.

PMID- 16295537
TI  - Discrimination of Aedes aegypti (Diptera: Culicidae) laboratory lines based on
      wing geometry.
AB  - Recent techniques of geometric morphometrics were applied to the study of four
      Thailand laboratory lines of the dengue vector Aedes aegypti. These lines
      differed by their geographic origin and the number of generations spent in the
      laboratory. Using a phase contrast microscope, a set of sixteen landmarks of the
      wings could be identified. A subsequent Procrustean superposition analysis
      produced the corresponding size and shape variables which were statistically
      analyzed. Size showed a significant decrease with the number of generations spent
      in the laboratory. Shape allowed an almost perfect reclassification of the
      specimens. This tool is able to accurately distinguish different laboratory lines
      and will be useful in field studies related to entomological surveillance and
      vector control.

PMID- 16295536
TI  - Paragonimiasis in Nan Province, northern Thailand.
AB  - Two cases of paragonimiasis were identified within the hill-tribe population
      living on the Thai-Laotian border of Nan Province, northern Thailand, where
      information on Paragonimus was then still limited. The patients were in the habit
      of eating improperly cooked crabs and freshwater prawns. A survey for natural
      intermediate hosts to complete the life cycle was in progress at that time, and
      the detection of paragonimiasis cases indicated that there was persistence of
      paragonimiasis in the endemic area of Nan Province.

PMID- 16295538
TI  - Determination of lead toxicity in Culex quinquefasciatus mosquitoes in the
      laboratory.
AB  - Laboratory investigations were carried out to study the effects of lead toxicity
      and lead uptake on Culex quinquefasciatus mosquitoes. Three different
      concentrations of lead nitrate were used in laboratory tests (0.05, 0.1, and 0.2
      mg/l). An atomic absorption spectrometer (AAS) was used to the determine lead
      concentrations. The results showed that lead significantly reduced hatching, egg
      production, and emergence rates, compared with the unexposed group (p < 0.05).
      The ratio of female to male offspring was 3.64:1, which was observed in the
      second generation, after the parents were exposed to 0.2 mg/l lead. No effects
      were observed on oviposition preference, larval weight, or larval deformation.
      The LC50 of lead against Cx. quinquefasciatus larvae within 24 hours was 0.18
      mg/l. There was a significant increase in lead uptake related to increased lead
      exposure in mosquito larvae (p < 0.05). The bioconcentration factor (BCF) showed
      that the lead concentration in the larvae was 62 times greater than in the water.
      The lead concentration from parents to offspring reduced in the first and second
      generations (p < 0.05). There was no significant difference between female and
      male mosquitoes in lead concentration (p > 0.05).

PMID- 16295539
TI  - First isolation of Japanese encephalitis from Culex quinquefasciatus in Thailand.
AB  - Isolation of Japanese encephalitis (JE) virus using C6/36 cell and
      immunofluorescence virus antigen detection techniques was attempted from female
      mosquitoes collected with CDC gravid traps in Samut Songkhram Province in the
      central region and in Phuket Province in southern Thailand, in 2003. One thousand
      and eighty female mosquitoes including 6 species of the Culicidae family (Culex
      quinquefasciatus, Cx. gelidus, Cx. tritaeniorhynchus, Cx. whitmorei, Cx. vishnui
      complex, Cx. s.g. culiciomyia) (pooled by specific specimen), were processed for
      virus isolation. Two pools of Cx. quinquefasciatus yielded a JE virus isolation.
      This represents the first report of JE virus isolation from Cx. quinquefasciatus
      in Thailand.

PMID- 16295540
TI  - Efficacy of a Bacillus thuringiensis israelensis tablet formulation, vectobac DT,
      for control of dengue mosquito vectors in potable water containers.
AB  - VectoBac DT, a tablet formulation of Bacillus thuringiensis israelensis (Bti) was
      evaluated for the potential control of dengue vectors in various types of potable
      water containers. On introduction to containers, the tablet sinks to the bottom
      and the Bti toxins are found concentrated at the sides and the base, while the
      treated water column is free of Bti toxins within 24 hours after tablet
      introduction. In a simulated study, earthen, HDPE and plastic containers were
      kept covered and laboratory-bred larvae were introduced to determine the control
      by the tablet. The efficacy and persistence of the tablet, with a control of >
      90%, was significantly longer in earthen containers in comparison to the HDPE and
      plastic containers. Efficacy and persistence were observed in earthen containers
      for a minimum period of 5.5 months (166 days) both without water replenishment
      and with weekly, 50% water volume, replenishment, and for a maximum period of 2.2
      months (66 days) with daily, 50% water volume, replenishment. In plastic and HDPE
      containers, the tablet activity had a persistence of 2.1 months (63 days) without
      water replenishment and 1.8 months (54 days) with weekly water replenishment. The
      efficacy and persistence of the VectoBac DT was significantly longer in the
      earthen containers, with or without regularly treated water exchange, due to the
      Bti toxins being embedded in the porous earthen container surfaces, which
      protects them from rapid degradation. Lesser toxin amounts are removed from the
      water column during water exchange. The efficacy of VectoBac DT was also
      evaluated for the control of natural infestation of Aedes larvae which were
      resistant to temephos at the WHO diagnostic dosage of 0.012 mg/l. The tablet
      significantly reduced the pupal density by 8 fold in earthen containers for 67
      days and 5 fold in HDPE containers for 55 days in comparison to untreated
      containers (p < 0.05). However, the tablet was effective for a shorter period of
      25 days post-tablet-introduction due to fungal infestation in the treated plastic
      containers. There is a need to determine the capacity of the VectoBac DT to
      reduce the dengue vector population to a threshold which will prevent dengue
      outbreaks in dengue endemic areas.

PMID- 16295541
TI  - Effect of microwave irradiation on the blow fly Chrysomya megacephala (F.)
      (Diptera: Calliphoridae).
AB  - Chrysomya megacephala (F) is a blow fly species of medical importance, being
      pestiferous and a mechanical carrier of various microorganisms to human food.
      Various strategies to reduce the fly population in endemic areas are needed. We
      investigated the effects of microwaves at 2,450 MHz, with third-instar exposure
      times of 7, 10, 15, 30 and 60 seconds on the larvae. Survival of the larvae was
      monitored by their emergence. About 60% of the larvae lived after 7 seconds of
      exposure, most died by 15 seconds, and all were dead at 30 and 60 seconds. The
      number of survivals decreased with increasing exposure times. This indicates the
      effect of microwave irradiation on fly larval survival.

PMID- 16295542
TI  - DHF in infants, late infants and older children: a comparative study.
AB  - A comparative study of dengue hemorrhagic fever in infants and children was
      conducted at the Department of Pediatrics, Phetchabun Hospital between May,1999
      and December, 2002. There were 1,924 DHF patients (aged 0-14 years). There were
      40 (2.1%) infants (age 0-l years) and 27 (1.4%) young children (age 1-2 years).
      Sixty-seven cases (3.5%) of the older children (> 2-14 years) were selected to be
      compared. The clinical and epidemiological data for each of the three groups were
      not statistically different from each other, except for age, splenomegaly, shock
      state and mode of dengue infection. Older children were more likely to have a
      second dengue infection and a shock state than younger patients. Laboratory
      investigation results and fluid management for each of the three groups were not
      significantly different from each other except for the total WBC (min),
      neutrophils (max), lymphocytes (max) and platelets (min). The platelets (min) in
      the infants were significantly lower than in the younger children and the older
      children. Associated symptoms, diseases, complications, and hematologic
      manifestations in each of the three groups were not significantly different from
      each other except for the presence of coryza, seizures, nausea/vomiting, rash,
      and petichiae. Coryza, seizures, nausea/vomiting, rash, and petichiae in the
      infants and younger children were significantly different from the older
      children.

PMID- 16295543
TI  - Structure-activity relationships of dengue antiviral polycyclic quinones.
AB  - The virucidal and antiviral photoactivities of three compounds, hypericin,
      tetrabromohypericin and gymnochrome B, were evaluated against dengue viruses. All
      the three products were active, and both the virucidal and antiviral activities
      were enhanced by light. Gymnochrome B was more potent than hypericin and
      tetrabromohypericin. The presence of the side chains on the hypericin core of
      gymnochromes appears to be beneficial for both virucidal and antiviral
      activities. This enhanced activity is likely to be linked to a complementary
      mechanism independent of photoactivation.

PMID- 16295544
TI  - Influenza surveillance in Pune, India, 2003.
AB  - Influenza surveillance was conducted in Pune, India in 2003. A total of 573
      throat swabs/ nasal swabs (TS/NS) and 190 nasopharyngeal aspirates (NPA) were
      collected from 763 in- and out-patients who were mostly children aged 0-16 years.
      TS/NS (507/573) and NPA (42/190) specimens were processed in MDCK cell cultures
      and identified with the hemagglutination inhibition test (HI). A total of 37
      influenza viruses was isolated: twenty-three type A (H3N2) and 14 type B of the
      Yamagata lineage were isolated from 29 children and 8 adults. Three type A (H3N2)
      isolates were characterized as being similar to A/Panama/2007/99 like,
      A/Korea/770/2000 like, and B/Sichuan/379/99 like strains.

PMID- 16295545
TI  - Intratypic variations among Thai herpes simplex virus (HSV) isolates determined
      by restriction fragment length polymorphism (RFLP) analysis.
AB  - Whole genomic polymorphisms for 20 HSV-1 and 20 HSV-2 isolates from Thai patients
      were analyzed by means of Restriction Fragment Length Polymorphism (RFLP)
      analysis using 4 restriction endonucleases: BamHI, Kpnl, HindIII, and EcoRI.
      Variations in cleavage sites among the HSV-1 and HSV-2 isolates were compared to
      the cleavage patterns of standard HSV-1 strain KOS and HSV-2 strain Baylor 186.
      Although 70% of HSV-1 isolates with BamHI digestion, 50% with Kpnl, 75% with
      HindIII and 70% with EcoRI digestion were found to be similar to the standard HSV
      1 (KOS) pattern, new BamHI restriction sites were detected in some HSV-1
      isolates. For HSV-2 isolates, 85% had the same pattern as the standard HSV-2
      (Baylor 186) after digestion with BamHI, HindIII, and EcoRI. No difference was
      observed with Kpnl digestion. When the patterns from the 4 enzymes were combined,
      HSV-1 isolates showed more divergence than the HSV-2 isolates. HSV-1 isolates
      found in both non-genital and genital lesions had more variety than the HSV-2
      isolates. This suggests that intratypic variations in HSV-2 are fewer than in HSV
      1.

PMID- 16295546
TI  - Detection of H. pylori in dyspeptic patients and correlation with clinical
      outcomes.
AB  - The objectives of this study were to evaluate the methods used to diagnose
      Helicobacter pylon infection in gastric biopsies, and to evaluate the correlation
      between H. pylori infection and clinical outcomes. Gastric biopsies, obtained
      from 210 patients, were evaluated for H. pylori by culture, a commercial rapid
      urease test (RUT, Pronto Dry) and histological examination. A true positive
      result was either the culture or both the RUT and histological examination were
      positive. The results showed a H. pylori infection rate of 44.3% (93/210). The
      sensitivities, specificities, positive predictive values and negative predictive
      values were 88.2, 100, 100, and 91.4 % by the culture; 95.7, 98.3, 97.8, and
      96.6% by RUT; and 96.8, 59.8, 59.8, and 65.7% by histological examination,
      respectively. The prevalences of H. pylori in non-ulcer dyspepsia (NUD), peptic
      ulcer dyspepsia (PUD) and gastric cancer (GCA) patients were 41.2, 57.9 and
      70.6%, respectively. The chi-squared-test showed that GCA patients were
      significantly more frequent infected with H. pylori than NUD patients (p<0.05).
      Our study indicates that the RUT method was highly sensitive, specific and
      appropriate for routine clinical use.

PMID- 16295547
TI  - Expression of cytokines and monosaccharide transporters in the duodenal mucosa of
      patients with gastrointestinal symptoms in rural Thailand.
AB  - Levels of cytokines and GLUT family monosaccharide transporters in the duodenal
      mucosa were examined in patients from Nong Khai, Thailand, who had underwent
      gastroscopy because of gastrointestinal problems. Duodenal biopsy specimens were
      collected from a total of 33 patients (24 males and 9 females, 45.0 +/- 13.5
      years old). Ten patients had present or recent intestinal helminth infections,
      including strongyloidiasis, taeniasis or ascariasis (group A), 7 were urease-test
      positive, indicating Helicobacter pylori infection (group B), and 16 had neither
      helminth infections nor urea-test positivity (group C). Total RNA was extracted
      from the biopsied specimens and a semi-quantitative RT-PCR was performed. The
      positivities for IL-13, IL-5 and IFN-gamma mRNA expressions in the patients were
      24.2, 60.6 and 100%, respectively, with the highest IL-13 and IL-5 positivities
      in group A, followed by group C and B. The IL-5 positive rate was significantly
      higher among patients with high peripheral blood eosinophil counts (> 4%) than in
      patients with low peripheral blood eosinophil counts. GLUT-1 and GLUT-5 were
      detectable in all the patients. Although GLUT-1 expressions did not differ among
      groups A, B and C. GLUT-5 expressions were significantly lower in group B than in
      group C. These results indicate that helminth and H. pylori infections result in
      different immunopathological responses in the duodenal mucosa, lower expressions
      of type 2 cytokines and monosaccharide transporters in H. pylori infections than
      in helminth infections.

PMID- 16295548
TI  - Characterization of diarrheagenic Escherichia coli isolated from food in Khon
      Kaen, Thailand.
AB  - Four categories of 186 ready-to-eat food samples in Khon Kaen municipality,
      Thailand, were collected and investigated for fecal contamination by enumeration
      of Escherichia coli using the most probable number (MPN) method. Then, the E.
      coli isolates were presumptively identified as diarrheagenic E. coil by
      agglutinating with polyvalent O-antisera and monovalent O-antisera commonly found
      in diarrheagenic strains and were subsequently investigated for the presence of
      the recognized virulence genes for enteroaggregative (EAEC), enteroinvasive
      (EIEC), enteropathogenic (EPEC), enterotoxigenic (ETEC), and shiga toxin
      producing E. coli (STEC or EHEC) by multiplex PCR assays. All E, coli isolates
      were examined for antimicrobial susceptibilities by the agar disc diffusion
      method, and the results were compared with those obtained from clinical samples.
      The percentage of each type of food with E. coli, including no heat food, low
      heat food, high heat food, and fruit juices and beverages, was higher than
      accepted standards at 60.4, 46.5, 38.6 and 20%, respectively. Of 140 E. coli
      isolates obtained from food samples, 11 isolates (7.9%) agglutinated with 6
      monovalent O-antisera, including one isolate each of O6, O8, O114 and O159, two
      isolates of O1, and five isolates of O157. None of the 11 isolates harbored the
      virulence genes for EPEC, ETEC, EAEC, EIEC and STEC. Although O157 E. coli
      isolates were found, the most frequent, E. coli O157:H7, was not found in this
      study. The astA gene, however, was found in 1 E. coli isolate that showed weakly
      positive agglutination against the polyvalent antisera. Approximately 50% of the
      140 E. coli isolates were resistance to at least one antimicrobial agent. The
      resistant strains showed high resistance to tetracycline (43%), co-trimoxazole
      (36%), ampicillin (26%) and chloramphenicol (23%), respectively. The resistance
      of E. coli was high for nearly all antimicrobial agents, particularly ampicillin
      (76%), tetracycline (70%), co-trimoxazole (69%) and nalidixic acid (44%). The
      results show that nearly half of the ready-to-eat food samples evaluated in Khon
      Kaen Municipality had levels of E. coli higher than acceptable standards. Of the
      diarrheagenic E. coli classified by serogroup, almost none of the isolates had
      virulence genes. These results indicate the disadvantage of relying on
      serogrouping alone for the recognition of diarrheagenic E. coli. E. coli isolated
      from food may not be an enteropathogenic strain. We also found that E. coli
      antimicrobial resistant strains are widespread in both food and humans.

PMID- 16295549
TI  - Characterization of vibrio parahaemolyticus isolated from coastal seawater in
      peninsular Malaysia.
AB  - Twenty-one Vibrio parahaemolyticus isolates representing 21 samples of coastal
      seawater from three beaches in peninsular Malaysia were found to be sensitive to
      streptomycin, norfloxacin and chloramphenicol. Resistance was observed to
      penicillin (100%), ampicillin (95.2%), carbenicilin (95.2%), erythromycin
      (95.2%), bacitracin (71.4%), cephalothin (28.6%), moxalactam (28.6%), kanamycin
      (19.1%), tetracycline (14.3%), nalidixic acid (9.5%) and gentamicin (9.5%).
      Plasmids of 2.6 to 35.8 mDa were detected among plasmid-containing isolates. All
      isolates carried the Vp-toxR gene specific to V. parahaemolyticus and were
      negative for the tdh gene, but only one isolate was positive for the trh gene.
      DNA fingerprinting of the isolates using ERIC-PCR and PFGE showed that the
      isolates belong to two major clonal groups, with several isolates from different
      locations in the same group, indicating the presence of similar strains in the
      different locations.

PMID- 16295550
TI  - Tuberculosis in HIV/AIDS patients: a Malaysian experience.
AB  - This retrospective study was conducted at the National Tuberculosis Center (NTBC)
      where 252 HIV-positive patients coexisting with tuberculosis (TB/HIV) were
      examined. We found that patients with pulmonary (PTB) and extrapulmonary
      tuberculosis (EPT) had similar mean age. A higher sex ratio between male to
      female (10.7:1) was observed in patients with PTB. The other characteristics of
      patients with pulmonary and extrapulmonary tuberculosis were not statistically
      different from each other. Cough (88%) and hemoptysis were the most common
      presenting symptoms, significantly related to patients with PTB. Lymphadenopathy
      (33.5%) was the most common sign in patients with EPT. The majority of patients
      with pulmonary and extrapulmonary tuberculosis had CD4 cell counts of less than
      200 cells/mm3 (range 0-1,179 with a median of 57 cells/mm3). Lung (89%) and
      miliary (55.6%) forms were the most frequent disease locations in patients with
      PTB and EPT, respectively. A higher percentage of patients with PTB (42%) were
      treated successfully with short-course (6 months) therapy, whereas in patients
      with EPT (43%) needed a longer period (9 months) for successful treatment. Of the
      patients who defaulted treatment, a higher proportion (87%) had PTB. No MDR-TB or
      relapse cases were found in this study.

PMID- 16295551
TI  - Antimicrobial resistance among Clostridium perfringens isolated from various
      sources in Thailand.
AB  - Antimicrobial resistance among Clostnridium perfringens isolated from feces of
      humans and pigs, food and other environmental sources was examined by testing of
      201 PCR-confirmed strains for resistance to 7 antimicrobial agents. The minimal
      inhibitory concentrations (MICs) were determined by the agar dilution method.
      Overall, C. perfringens showed the highest resistance to tetracycline (56.2%),
      followed by imipenem (24.9%), metronidazole (9.5%), penicillin G (9%), vancomycin
      (4.5%), chloramphenicol (3%) and ceftriaxone (1%). The majority of the isolated
      strains from pig feces (77.8%), environment (72.7%), human feces (44.9%) and food
      (28%) showed resistance to tetracycline. Strains isolated from human feces only
      showed low resistance to ceftriaxone (2.5%) and vancomycin (10.1%). Penicillin G
      had high activity, with overall MIC50 and MIC90 of 0.06 and 1.0 microg/ml,
      respectively, and low rate of resistance (10-12% for strains isolated from
      humans, animals and food). Among 62.7% of antimicrobial resistant strains, 39.3%
      were resistant to a single drug and 23.4% were multiple-drug resistant (MDR). Of
      overall 47 MDR strains, 63.8% were derived from human feces and were resistant to
      two to six drugs.

PMID- 16295552
TI  - Species prevalence and antimicrobial susceptibility of enterococci isolated in a
      tertiary care hospital of North India.
AB  - The present prospective study was carried out to determine the species
      distribution and antimicrobial susceptibilities of enterococci isolated from
      clinical samples in a tertiary care hospital of North India. Enterococcus species
      isolated from blood, urine, pus, sterile fluids and the hospital environment from
      October 2003 to January 2004 were identified by standard biochemical tests.
      Antimicrobial susceptibility testing was performed by the disk diffusion method
      as per NCCLS guidelines. Out of a total of 105 Enterococcus species recovered
      during the study period, E. faecium (42.90%) and E. faecalis (40.00%) constituted
      the predominant isolates. Enterococcus faecium was the commonest blood culture
      isolate while E. faecalis predominated pus and urine samples. Other species
      isolated were E. mundtii, E dispar, E. durans, E. avium, E. raffinosus and E.
      gallinarum. High-level aminoglycoside resistance was detected in 73.3% of
      isolates. Resistance to vancomycin, teicoplanin and linezolid was not detected.
      Prevalence of a wide variety of Enterococcus species in clinical samples together
      with their variable antimicrobial susceptibility patterns emphasizes the need for
      routinely carrying out detailed speciation and in vitro susceptibility testing of
      enterococcal isolates in the clinical bacteriology laboratory.

PMID- 16295553
TI  - Production of a monoclonal antibody against a yeast secreted antigen of
      Penicillium marneffei.
AB  - Monoclonal antibody against P. mameffei yeast secreted antigen was produced in
      order to develop a serological test for penicilliosis marneffei. The yeast form
      of P. marneffei was cultured in brain heart infusion broth at 37 degrees C for 7
      days. A secreted antigen was prepared, partially purified from culture
      supernatant and subsequently immunized in a BALB/c mouse. Mouse monoclonal
      antibody was produced from immune spleen cells by a standard hybridoma technique.
      Specificity of the obtained monoclonal antibody was assessed with yeast secreted
      antigens for P. mameffei, C. alblicans, C. neoformans, and H. capsulatum by an
      indirect ELISA. Three of 46 hybrid clones (1 F1, 2G5, and 3G4) reacted positively
      with P mameffei secreted antigen. 1 F1 and 3G4 were cloned by two rounds of
      limiting dilution. Partially purified monoclonal antibody and rabbit polyclonal
      antibody against P. marneffei yeast secreted antigen were used to develop a
      double antibody sandwich ELISA to detect P. marneffei antigen in plasma or serum
      samples of 7 patients with penicilliosis marneffei and 5 healthy controls. The
      sandwich ELISA developed using monoclonal antibody as a capture antibody and
      rabbit polyclonal antibody as a detector was able to detect P. marneffei antigen
      in all the plasma and serum samples of penicilliosis marneffei patients, while
      negative in all the healthy controls. Thus, the monoclonal antibody produced in
      the present study appeared to be highly specific for P. marneffei and the double
      antibody sandwich ELISA developed using monoclonal and polyclonal antibodies
      against the yeast secreted antigen of P. marneffei showed a strong potential for
      the diagnosis of penicilliosis marneffei.

PMID- 16295554
TI  - A lyophilized formulation to extend the shelf-life of tuberculin PPD.
AB  - This study was aimed to develop a dry purified protein devirative (PPD)
      preparation to extend the shelf-life of tuberculin PPD. Five percent sucrose (S),
      6.5% mannitol (M), 2.5% trehalose (T) or 0.3% Hemaccel (H) was added to each
      formulation. In vivo and in vitro analyses were carried out to determine the
      efficacy of the lyophilized products. In the in vivo test, the delayed type
      hypersensitivity (DTH) responses of the lyophilized preparations were compared to
      the liquid preparation (CL) after injection into BCG vaccinated guinea pigs. The
      preparations of H, M, T, and S generated DTH responses of 100, 90, 89, and 60%,
      as compared to the response of CL, respectively. There was no loss of tuberculin
      activity in the H formula. A statistically significant difference in activity was
      found between S and CL (p < 0.05). The cellular test for IFN-gamma secretions was
      performed using the whole blood of human subjects screened for DTH response to
      tuberculin PPD Mantoux tests. The detection of IFN-gamma secretions was done
      using ELISA and the efficacy was expressed in terms of percentage of IFN-gamma
      responses to the tuberculin antigens. The results of CL, H, M, T and S were 3.28,
      10.40, 0.84, 1.52 and 1.29%, compared to mitogen stimulation, respectively. The
      lyophilized H, M and T formulations and the liquid CL were studied for their
      shelf-life stabiliy. Accelerated degradation was done by storing the samples at
      higher temperatures of 37 degrees C and 56 degrees C for 3, 6, 9 and 12 months.
      All the tuberculin PPD solutions were injected into BCG vaccinated guinea pigs at
      the end of each storage period and the activity of each solution was evaluated.
      The formulation with the Hemaccel as excipient gave a superior response than the
      others at the normal storage temperature of 40 micro C for 12 months. Therefore,
      Hemaccel provides protection for PPD activity. This supports the potential for
      the development of lyophilized tuberculin PPD with the addition of 0.3% Hemaccel
      to extend shelf life.

PMID- 16295555
TI  - Use of the WHO hemoglobin color scale in family welfare clinics in India.
AB  - A situation is reported for the use of the WHO color scale for the measurement of
      hemoglobin, which was introduced into India in 1996. Charity family welfare
      clinics held at a medical college hospital in North India offer free
      sterilization by tubal ligation under local anesthetic to women following a
      preliminary screening. An obligatory test of the hemoglobin level is required and
      must be above 7.0 g/dl for the operation. Some clinics attract large numbers, and
      the card gives a cheap, rapid and reasonably accurate test, adding to the smooth
      running and reduction of waiting time. It has proved satisfactory over a 2-year
      period; 2.3% of participants were shown to have a hemoglobin level of 7 g/dl or
      less.

PMID- 16295556
TI  - Pyomyoma in a postmenopausal woman: a case report.
AB  - Pyomyoma (suppurative leiomyoma of the uterus) is a rare condition associated
      with a high fatality rate. Only surgical intervention is lifesaving. It usually
      develops in association with either recent pregnancy or in postmenopausal
      patients who have underlying vascular disease. Since 1945 only 15 cases of
      pyomyoma have been reported in the literature. We present a rare case of pyomyoma
      in a 64-year-old woman with a brief review of the literature.

PMID- 16295557
TI  - Which mild head injured patients should have follow-up after discharge from an
      accident and emergency ward? A study in a university hospital setting in
      Kelantan, Malaysia.
AB  - Mild head injury (MHI) is a common presentation to many hospitals in both rural
      and urban settings in Southeast Asia, but it is not well studied. We studied 330
      patients that presented to Hospital Universiti Sains Malaysia Emergency
      Department with possible MHI, with the intentions to identify prognostic factors
      that may improve the diagnosis of MHI in the emergency setting as well as to
      determine which patients would need follow-up. Patients' one-year outcomes were
      classified as discharged well (DW) for patients without post-traumatic signs and
      symptoms and discharged with long term follow-up (DFU) for patients with such
      signs and symptoms. Four patients died and 82 were DFU. An abnormal skull X ray
      was associated with mode of accident and type of transportation, older age,
      presence of vomiting, confusion, bleeding from ear, nose or throat, abnormal
      pupil size on the right side associated with orbital trauma, unequal pupillary
      reflexes, absence of loss of consciousness (LOC), a lower Glasgow Coma Scale
      (GCS) score, multiple clinical presentations, and DFU. An abnormal CT scan was
      associated with older age, multiple clinical presentation, skull X-ray findings,
      and DFU. A similar analysis on outcomes revealed that mode of accident, older
      age, vomiting, confusion, headache, bleeding from ear, nose and throat,
      neurological deficits, absence of LOC, pupil size, multiple presentation,
      abnormal skull X ray, CT scan of the brain, and a GCS of 13 was associated with
      DFU. In conclusion, all patients involved in motor vehicle accidents (MVAs),
      especially motorcycles, aged over 30 years of age, with multiple clinical
      presentations, including a lower GCS, and with abnormal radiological findings
      should have a longer follow-up due to persistent post-traumatic symptomatology.

PMID- 16295558
TI  - Survival of patients with advanced non-small-cell lung cancer at Ubon Ratchathani
      Cancer Center, Thailand.
AB  - This survival analysis was conducted at Ubon Ratchathani Cancer Center to
      determine the prognostic factors for survival of patients with stage IIIA, stage
      IIIB, and stage IV non-small-cell lung cancer (NSCLC) patients treated at the
      center between 1997-2001. The study sample included 210 patients with non-small
      cell lung cancer. Diagnosis and staging were defined employing the TNM system.
      The majority of lung cancer patients were smokers (66.7%), lived in Ubon
      Ratchathani Province (40.0%), male (77.6%), and agriculturalists (74.8%). Seventy
      seven percent of patients died within five years, 19.5% were lost to follow-up
      and 2.9% were still alive in 2003. The estimated median survival time was 6.3
      months (95% CI 5.4-7.3); the median survival times for stages IIIA, IIIB, and IV
      were 16.3, 7.0, and 4.5 months, respectively. The overall 1-, 2- and 3-year
      survival rates of NSCLC were 28.9, 7.9, and 3.3, respectively. The differences in
      survival of patients in the various stages of the disease were statistically
      significant (p < 0.0001), adjusted for age and sex. Treatment with combination
      methods and at an early stage in the disease were associated with significant
      prolongation of survival. For stage IIIA, the estimated median survival times by
      treatment with chemotherapy was 7.0 months, radiotherapy was 16.0 months, surgery
      and others 16.3 months, and chemotherapy plus radiotherapy was 19.5 months.
      However, only chemotherapy versus surgery and others was significantly different
      (p = 0.0307). The median survival times for stage IIIB patients treated with
      chemotherapy, radiotherapy, surgery and others, chemotherapy and radiotherapy,
      and supportive treatment were 7.0, 7.0, 9.0, 14.7, and 3.0 months, respectively.
      The differences between surgery and others versus supportive treatment,
      chemotherapy and radiotherapy versus supportive treatment were significantly
      different (p = 0.0392, p = 0.0433, respectively). For stage IV, the median
      survival times for patients treated with chemotherapy, radiotherapy, chemotherapy
      and radiotherapy, and supportive treatment were 5.0, 4.3, 6.5, and 1.0 months,
      respectively. The differences between chemotherapy, radiotherapy, chemotherapy
      and radiotherapy versus supportive treatment, all were significantly different (p
      = 0.0020, p < 0.0001, p < 0.0001, respectively). The 2-year survival rates for
      stages IIIA, IIIB, and IV were 16.0, 4.1, and 2.2%, respectively. The results of
      the study show that stage IIIA has the longest survival time. They also show that
      appropriate treatment is a significant factor in improving the survival of lung
      cancer patients.

PMID- 16295559
TI  - Utility of gamma-glutamyl transpeptidase and mean corpuscular volume in alcoholic
      liver disease.
AB  - The present study was designed to establish the role of Gamma-glutamyl
      transpeptidase (gamma-GT) and mean corpuscular volume (MCV) in alcoholic liver
      disease (ALD). Serum gamma-GT, total and direct bilirubin, albumin, total
      protein, AST, ALT and ALP were assayed by standard methods in a clinical
      chemistry autoanalyser. MCV, Hb, PCV and RBC were measured by an automated cell
      counter. Activity of gamma-GT and MCV levels were significantly higher in the
      patients with ALD compared to controls. A gamma-GT level of > or = 25 U/l was
      found to be significantly associated with ALD. MCV level > or = 100 fl/l showed a
      significant association with ALD. An AST to ALT ratio > 1 was found in 92% of the
      patients. None of the patients showed an ALT level > or = 300 IU/l. The degree of
      AST elevation in the patients with ALD was higher (3.7 times) then ALT (3.2
      times). A gamma-GT level > or = 25 IU/L and an MCV level > or = 100 fl/l stand as
      markers of heavy alcohol consumption in this study. An AST to ALT ratio > 1 was
      present in most of the patients with ALD. The degree of elevation of AST was
      higher than ALT in the patients with ALD.

PMID- 16295560
TI  - A re-evaluation of plasma sialic acid determination using the periodate
      resorcinol method versus the enzymatic method.
AB  - The concentration of plasma sialic acid was estimated using the modified chemical
      method and the more sensitive enzymatic method in 20 subjects with impaired
      glucose tolerance and 20 control subjects. The mean sialic acid concentration
      values of the control subjects and subjects with impaired glucose tolerance using
      the enzymatic method were 1.747 +/- 0.047 and 2.583 +/- 0.070 mmole/l and 1.753
      +/- 0.067 and 2.591 +/- 1.02 mmole/l for the chemical method. The intra-assay
      coefficient of variation for the control subjects and for the subjects with
      impaired glucose tolerance were 1.963% and 1.583%, respectively, for the
      enzymatic assay and 2.728% and 2.431%, respectively, for the chemical assay. The
      inter-assay coefficient of variation for the control subjects and for the
      subjects with impaired glucose tolerance were 2.686% and 2.723% for the enzymatic
      assay, and 3.819% and 3.95% for the chemical assay. Since the values do not
      differ significantly, the chemical assay is a cost effective method that can be
      used in large epidemiological studies.

PMID- 16295561
TI  - Factors affecting the experiences of drug use by adolescents in a Bangkok slum.
AB  - The purpose of this research was to study the demography, financial status,
      social status, knowledge of amphetamines, perceived harmfulness of amphetamines,
      and life skills in the prevention of drug abuse in adolescents. The factors
      leading to drug use among young people were also studied. The study group was
      composed of 354 subjects aged 12 to 22 years, living in 2 slums in Bangkok. The
      research showed that about 7% of the sample group had used drugs before. Four
      percent had never used drugs, but someone had tried to talk them into using them.
      Almost 20% had friends who had used drugs, and 11% had friends who were still
      using drugs. About 13% of the adolescents in the study group had family members
      who used drugs and another 9% had family members who were still using drugs. In
      our study, we found that the most common drug group was amphetamines. On average,
      the participants had a low level of understanding about drug abuse, especially of
      the symptoms, side effects, and legal penalties. Most of the adolescents realized
      how harmful amphetamines and other drugs were and had a high degree life skills.
      Factors influencing adolescent drug use were (1) personal factors, such as
      monthly income/allowance and life skills; (2) family environment, such as drug
      abuse history in the family; and (3) social environment, such as a drug abuse
      history among friends. When studying the life skill factors of the adolescents,
      which is an independent factor capable of influencing the experience with drugs,
      the researchers found that the time spent with other members of the family and
      the family members' drug experiences were the only factors leading to life skills
      in the prevention of drug abuse in adolescents. In addition to letting children
      learn on their own, training them to acquire life skills is beneficial when faced
      with problematic situations. Creating relationships between adolescents and other
      members of the family, friends, and society can increase their life skills,
      diminishing the risk of drug abuse.

PMID- 16295562
TI  - Prescription pattern for treatment of hemorrhoids under the universal coverage
      policy of Thailand.
AB  - The Universal Coverage Policy (UCP) or "30 Baht Scheme" was launched in Thailand
      in 2001. The policy caused a cutback in the budgets of all public hospitals and
      health service centers. Traditional medicine was then viewed as an alternative to
      save costs. This study examines whether this had any influence on hemorrhoid
      treatment prescription patterns, ratio of traditional/modern medicine, or the
      cost of hemorrhoid treatment after the UCP was implemented at a community
      hospital. The traditional medicine prescribed was Petch Sang Kart and the modern
      alternative was Proctosedyl. All hemorrhoid prescriptions at a community hospital
      from October 2000 to January 2003 were surveyed. Segmented Regression Analysis
      was applied to evaluate prescription trends, the ratios between the types of
      medicine, and the hemorrhoid treatment cost. A total of 256 prescriptions were
      analyzed. The average number of traditional medicine prescriptions per month were
      more than modern medicine (41 versus 16). During the study period, the trend of
      modern medicine use and the treatment cost was decreased (p < 0.01). The ratio of
      traditional/modern medicine increased 0.2 times (p = 0.02).

PMID- 16295563
TI  - Water supplies in some rural communities around Calabar, Cross River State,
      Nigeria: bacteriology of drinking waters.
AB  - Several communities in Nigeria exist without regular water supplies of good
      quality and quantity. Despite this situation, successive governments have tended
      to ignore the problem. The water supplies to two rural communities 7-8 km north
      of Calabar, Cross River State of Nigeria, were examined bacteriologically using
      standard indicator bacteria (coliforms and streptococci). A contiguous community
      supplied with treated piped water was also studied in parallel. The rural water
      supplied was found to be bacteriologically unsatisfactory, having failed to meet
      the international standards for drinking water as set by the WHO. The geometric
      mean bacterial counts per 100 ml of serial samples from six sources ranged from
      0.12 x 10(1) to 1.57 x 10(2) for fecal coliforms (E. col) and 0.05 x 10(1) to 7.5
      x 10(1) for the fecal streptococci. Fecal streptococci were particularly
      recovered in large numbers from one source (Ayip Asikimangfuk) at concentrations
      of up to 3.0 x 10(2) per 100 ml at the onset of the rains. The water supplies
      from the community with piped water were, in general, bacteriologically
      satisfactory; fecal coliforms were found only in occasional samples (0.12 x
      10(1)/100 ml).

PMID- 16295564
TI  - Water supplies in some rural communities around Calabar, Cross River State,
      Nigeria: impact on water-related diseases.
AB  - Two traditional surface water sources and one piped supply around Calabar,
      Nigeria were examined to reveal the community water use patterns and the impact
      on water-related diseases. Using questionnaires, it was shown that some
      communities trekked long distances (up to 5 km) to reach their supply source. The
      quantity of water collected per day in each of the five rural sources was
      inadequate (approximately 6 buckets or 90 liters). The traditional water sources
      were not available all year round, forcing users to trek longer distances for
      alternative supplies. Only 4.4% of rural water users subjected them to any
      further treatment, such as boiling or filtration. Fetching water was the
      occupation of children; they were the worst hit by water-related diseases, such
      as diarrhea/ dysentery, stomachache, worms and scabies/craw-craw. About 84% of
      the respondents were dissatisfied with their water supplies. Deaths due to
      apparent water-related diseases occurred among 6.3% of respondents during the
      twelve months preceding the study. The overall impact was a loss of school
      hours/days, loss of labor and general discouragement. The community served with
      piped treated water fared better in all respects.

PMID- 16295565
TI  - Improving microbial air quality in air-conditioned mass transport buses by
      opening the bus exhaust ventilation fans.
AB  - The air quality in air-conditioned mass transport buses may affect bus drivers'
      health. In-bus air quality improvement with the voluntary participation of bus
      drivers by opening the exhaust ventilation fans in the bus was implemented in the
      Seventh Bus Zone of Bangkok Mass Transit Authority. Four bus numbers, including
      bus numbers 16, 63, 67 and 166, were randomly selected to investigate microbial
      air quality and to observe the effect of opening the exhaust ventilation fans in
      the bus. With each bus number, 9 to 10 air-conditioned buses (total, 39 air
      conditioned buses) were included. In-bus air samples were collected at 5 points
      in each studied bus using the Millipore Air Tester. A total of 195 air samples
      were cultured for bacterial and fungal counts. The results reveal that the
      exhaust ventilation fans of 17 air-conditioned buses (43.6%) were opened to
      ventilate in-bus air during the cycle of the bus route. The means +/- SD of
      bacterial counts and fungal counts in the studied buses with opened exhaust
      ventilation fans (83.8 +/- 70.7 and 38.0 +/- 42.8 cfu/m3) were significantly
      lower than those in the studied buses without opened exhaust ventilation fans
      (199.6 +/- 138.8 and 294.1 +/- 178.7 cfu/m3), p < 0.0005. All the air samples
      collected from the studied buses with opened exhaust ventilation fans were at
      acceptable levels (< 500 cfu/m3) compared with 4.6% of the air samples collected
      from the studied buses without opened exhaust ventilation fans, which had high
      levels (> 500 cfu/m3). Of the studied buses with opened exhaust ventilation fans
      (17 buses), the bacterial and fungal counts after opening the exhaust ventilation
      fans (68.3 +/- 33.8 and 28.3 +/- 19.3 cfu/m3) were significantly lower than those
      before opening the exhaust ventilation fans (158.3 +/- 116.9 and 85.3 +/- 71.2
      cfu/m3), p < 0.005.

PMID- 16295566
TI  - Strengthening the capability of family health leaders for sustainable community
      based health promotion.
AB  - The Family Health Leader (FHL) Project was initiated in 1997 to encourage self
      care and health promotion. Since then, there has been no retraining. This study
      aimed to strengthen the FHLs' capability to sustain community-based health
      promotion and network establishment. The study, of a quasi-experimental design,
      was conducted in a village in Phan Thong district, Chon Buri Province, Thailand.
      The intervention emphasized enhancing the FHLs' knowledge, ability, leadership
      and motivation to advance health promotion activities. Before implementing the
      main intervention, 5 community health workers were trained as facilitators to
      strengthen 36 FHL capabilities. The curriculum and manual for training
      facilitators and FHLs were also developed. The intervention for strengthening
      FHLs' capabilities lasted for 7 months using participatory training. A within
      subject repeated ANOVA was used to measure changes in the main outcome variables
      immediately, and at three and six months after the intervention. A qualitative
      methodology was utilized to assess network establishment. The results indicate
      that the FHLs' knowledge of self-care and health promotion, ability, leadership
      and motivation had increased significantly after the intervention (p < 0.001).
      The FHLs also sought to extend their network by involving both the community
      committee and the local authorities. The intervention appeared to be successful
      in strengthening the FHLs' capabilities to sustain health promotion within the
      community, and it established networks vertically and horizontally. The FHLs were
      the key persons to bring good health to family members. Periodical participatory
      learning and group empowerment are recommended for encouraging the FHLs to
      maximize their potential for family self-care and health promotion.

PMID- 16295567
TI  - Perceived industrial deafness and hearing loss among people in a small Queensland
      rural community.
AB  - This paper aims to describe chronic diseases including hearing loss reported by
      people in a small rural community. It will present the results of audiometric
      screening among a group of people in this community and their self reported risk
      factors of hearing loss. Different risk factors experienced by men and women will
      be compared. Two surveys were conducted in a small Queensland rural community.
      The first survey gathered information relating to chronic diseases among 604
      people using a telephone interview method. The second survey assessed the level
      of hearing among 64 people who presented themselves for audiometric screening,
      their history of exposure to loud noise and their previous use of hearing
      protective measures. A higher rate of "industrial deafness" was reported (110.75
      per 1,000 population) than the 1995 National rate (95.2 per 1,000 population). Of
      64 people who attended the audiometric assessment, 60 (93.8%) had some level of
      hearing loss using the 2000 International Standard of hearing level (ISO 7029:
      2000) taking age and gender into account. However, 15 persons (23.4%) perceived
      that they had good hearing. When compared to ISO 7029: 2000 standard, men and
      women had a similar pattern of hearing loss. Compared to men, a lower percentage
      of women were exposed to different sources of loud noise and were less likely to
      use hearing protection devices.

PMID- 16295568
TI  - Factors associated with obesity among workers in a metropolitan waterworks
      authority.
AB  - To examine the relationship of socio-demographic characteristics, psychological
      factors, knowledge, attitude and behavior towards obesity among Metropolitan
      Waterworks Authority (MWWA) officers, a cross-sectional study was conducted
      between July and September, 2004. Two hundred and eighty-eight obese [body mass
      index (BMI) > or = 25 kg/m2] and 106 non-obese persons, aged 20-60 years, were
      recruited as study subjects. Data were collected by a self-administered
      questionnaire, comprised of three parts: socio-demographic; psychological factors
      (depression and stress); and knowledge, attitude, behavior related to obesity.
      Univariate analyses and Logistic regression models were used to study the
      association between obesity and possible risk factors. The results demonstrate
      significant associations between older age and obesity. Volunteers in the age
      groups of 40-49 and 50-59 years had a significantly higher risk of being obese
      than the age group of less than 40 years (adjusted OR = 3.4, 95% Cl = 1.1-11.1
      and adjusted OR = 10.4, 95% CI = 3.3-32.7, respectively). Volunteers with
      unhealthy behaviors were at significantly higher risk than those with healthy
      behaviors (adjusted OR = 10.3, 95% CI = 2.0-52.4) while persons with moderately
      healthy behaviors also had increased risk, but to a lesser extent (adjusted OR =
      4.5, 95% CI = 1.7-11.4). There were no associations between psychological factors
      and obesity in this group of volunteers. When we focused on whether they consumed
      more food when they were stressed, it was found that the obese consumed
      significantly more food during stress (p-value = 0.003). Watching television,
      videos, or playing computer continuously for more than 3 hours, were
      significantly associated with obesity. We conclude that although the obese have a
      good knowledge and attitude towards obesity, they still practise unhealthy
      behavior, have a sedentary lifestyle, and over eat when they are stressed. Future
      research regarding behavioral modification should be implemented at both
      community and country levels.

PMID- 16295569
TI  - Induction of type I collagen and osteocalcin in human dental pulp cells by
      retinoic acid.
AB  - Retinoic acid has been known to play a key role in the regulation of bone cell
      differentiation and function. The effects of retinoic acid on human dental pulp
      cells, which contain several characteristics similar to those of bone cells, has
      yet to be elucidated extensively. The effects of retinoic acid on human dental
      pulp cells in terms of type I collagen and osteocalcin induction were
      investigated in vitro. Dental pulp cells obtained from the teeth of young
      patients (age between 18-22 years) were cultured and subsequently treated with
      various concentrations of retinoic acid (0, 10(-7), 10(-6), 10(-5) M) in serum
      free DMEM. At different time intervals (8, 12 and 24 hours), the levels of type I
      collagen and osteocalcin secreted were determined using Type I Procollagen C
      Peptide and Gla-type Osteocalcin EIA kits, respectively. Induction effects were
      evaluated using analysis of variance and the Duncan's multiple rank test.
      Retinoic acid at concentrations of 10(-5), 10(-6), 10(-7) M was able to induce
      type I collagen and osteocalcin production in human dental pulp cells within 12
      hours of exposure. Dose-dependent induction was observed only after 24 hours. A
      two-fold increase in osteocalcin level was detected after exposed to 10(-5) M
      retinoic acid within 24 hours. Our data suggest that retinoic acid at
      concentrations of 10(-5), 10(-6), 10(-7) M has the ability to induce type I
      collagen and osteocalcin secretions in human dental pulp cells in vitro.

PMID- 16295570
TI  - The hallmarks of a strong profession.

PMID- 16295571
TI  - Midwives' freedom of judgement.

PMID- 16295572
TI  - Pre-conception care and diabetes.

PMID- 16295573
TI  - Preventing infant allergies.

PMID- 16295574
TI  - Maternal breastfeeding positions: have we got it right?

PMID- 16295575
TI  - Expression of love.

PMID- 16295576
TI  - The milk of human kindness.

PMID- 16295577
TI  - The flukes of hazard.

PMID- 16295578
TI  - Midwifery basics: complications in pregnancy (2). Adult resuscitation.

PMID- 16295579
TI  - Clinical risk management (3): learning from experience.

PMID- 16295580
TI  - Outrage over PCT reform proposals.

PMID- 16295581
TI  - Alcohol: the impact on nursing.

PMID- 16295582
TI  - The legacy of post-war nursing.

PMID- 16295583
TI  - The use of counselling and leadership skills in cancer care.
AB  - Improving outcomes for patients is central to the delivery of cancer services. By
      focusing on improving the psychological well-being of patients it becomes very
      clear how important the link is between the appropriate use of counselling skills
      and effective nurse leadership.

PMID- 16295584
TI  - Ichthyosis.

PMID- 16295585
TI  - Blood cells. Part five--Platelets.

PMID- 16295586
TI  - Assessing and recording a patient's sexual history.
AB  - Ascertaining clients' sexual history is an important factor in identifying and
      managing their sexual health needs. This article presents an overview of the
      process and principles of taking a comprehensive history to assess risk regarding
      sexually transmitted infections and HIV, which can be applied and adapted to all
      health care settings.

PMID- 16295587
TI  - Clozapine.

PMID- 16295588
TI  - Implications of non-medical prescribing of controlled drugs.
AB  - Mental health nurses working in the substance misuse field will soon be able to
      prescribe controlled drugs as part of their role. This article discusses the
      implications of this and its potentially positive impact on the existing
      prescribing services.

PMID- 16295589
TI  - Single referrals for inpatient and community rehabilitation.
AB  - The introduction of a single system for inpatient and community rehabilitation
      stemmed from a desire to simplify access to rehabilitation services. It was
      intended that in turn this would ensure that more patients were assessed for
      their suitability. A specialist multidisciplinary team skilled in assessment
      would decide which model of rehabilitation would meet individual needs.

PMID- 16295590
TI  - Dedicated to supporting families.

PMID- 16295592
TI  - Standardised monitors to measure anaesthetic depth.

PMID- 16295591
TI  - Privatisation of community nursing will jeopardise public health and nurses'
      careers.

PMID- 16295593
TI  - Family costs.
AB  - Childcare allowances for nursing students are inadequate, inconsistent and
      complicated to obtain. With two in five nursing students a parent, attrition
      rates are bound to rise unless government addresses the imbalance.

PMID- 16295594
TI  - Sexual revolution.
AB  - The FPA--formerly the Family Planning Association--celebrates its 75th
      anniversary this year. Since its inception, the association's remit has broadened
      from the provision of contraceptive advice to health education and help with
      sexual dysfunction. Before contraceptive services became available, women
      underwent multiple pregnancies. Until 1967, contraceptive advice was available
      only to married women. Family planning nurses now provide women with the
      contraceptive pill as well as injections and emergency contraception. The FPA
      provides termination of pregnancy and vasectomy services.

PMID- 16295595
TI  - It's all the buzz.
AB  - Although honey has been used medicinally for thousands of years, bee products
      have only recently become the subject of in depth medical research. Wound healing
      products containing honey are now available. Bee venom has been used to treat
      painful conditions. Propolis is a potent anti-inflammatory agent. Broad claims
      have been made for royal jelly.

PMID- 16295596
TI  - Flu blues.
AB  - Flu is at best miserable and at worst can have serious complications. Children
      are as vulnerable to the infection as adults and in certain circumstances
      vaccination is recommended. Attack rates of the virus are highest in preschool
      and school age children. Symptoms in children are the same as in adults but may
      also be accompanied by nausea, vomiting and diarrhoea. Children are at higher
      risk of complications, especially otitis media. In England and Wales in 2003, 11
      children aged between one and four died from flu.

PMID- 16295597
TI  - Zero fire tolerance.

PMID- 16295598
TI  - Use of lubricant gels in urinary catheterisation.
AB  - Nurses with a prescribing qualification are now able to prescribe catheters and
      catheter management products. However, they must use research and best evidence
      to inform their prescribing decisions. This article reviews the catheterisation
      process and the use of lubricant gels in both transurethral (particularly in
      females) and suprapubic catheterisation. It also considers the benefits of
      lubricating gels.

PMID- 16295599
TI  - Developing and implementing a new bladder irrigation chart.
AB  - Continuous bladder irrigation is a widely used procedure following urological
      surgery. Nurses monitor patients to minimise complications and to provide an
      accurate record of fluid input and output. Through observation in practice and
      discussion with a ward team, it was identified that the documentation in use for
      recording fluid balance was inadequate. This resulted in inconsistencies and
      omissions in documentation, which led to inaccuracies in fluid balance.
      Development of a new chart has attempted to address these issues. It has been
      developed as a result of concerns identified in practice and adapted to meet the
      needs of the clinical area.

PMID- 16295600
TI  - Sustaining safe and acceptable bowel care in spinal cord injured patients.
AB  - This article aims to increase understanding of the bowel care needs of patients
      with spinal cord injury. Spinal cord injury centres provide expert bowel
      management for these patients but healthcare staff in general hospitals may not
      be familiar with the techniques required.

PMID- 16295601
TI  - Psychoactive substances.

PMID- 16295602
TI  - Identify your style.

PMID- 16295603
TI  - Public view.

PMID- 16295604
TI  - The end is in sight.

PMID- 16295605
TI  - The quality of patient experiences and the nursing contribution to patient
      outcomes.

PMID- 16295606
TI  - Vantage point.

PMID- 16295607
TI  - Spotlight on success. Liz Bray.

PMID- 16295608
TI  - Joined up thinking.

PMID- 16295609
TI  - Practical solutions.

PMID- 16295610
TI  - Moving the agenda forward.

PMID- 16295611
TI  - The Department of Health: championing investment and capacity building in nursing
      research.

PMID- 16295612
TI  - A Northern Ireland perspective.

PMID- 16295613
TI  - Nursing and midwifery research in Scotland.

PMID- 16295614
TI  - Achieving potential through research and development: a Welsh perspective.

PMID- 16295615
TI  - Going the extra mile.

PMID- 16295616
TI  - Mission impossible?

PMID- 16295617
TI  - Shared interests.

PMID- 16295618
TI  - Building research capacity.

PMID- 16295620
TI  - Will Michigan be "running on empty " by 2025?

PMID- 16295619
TI  - It's time for a change in how we discuss the periodontal diseases.

PMID- 16295621
TI  - Disposition of a dental practice upon the death of a dentist.

PMID- 16295622
TI  - Protecting social security numbers.

PMID- 16295623
TI  - Business insurance choices for young dentists.

PMID- 16295624
TI  - Financial services add value to your membership.

PMID- 16295625
TI  - Which claims are medical, and which are dental?

PMID- 16295626
TI  - The MDA/Blue Cross partnership: why the MDA uses Blue Cross Blue Shield as its
      health insurance program.

PMID- 16295627
TI  - Protecting your practice from internal fraud.

PMID- 16295628
TI  - How to make money when you're out of the office!

PMID- 16295629
TI  - "Give kids a smile" 2006: planning tips and timelines.

PMID- 16295630
TI  - Are there new federal rules for disposal of records?

PMID- 16295632
TI  - Create a "brand" new you.

PMID- 16295631
TI  - A smelly situation!

PMID- 16295633
TI  - Understanding the new Medicare prescription coverage.

PMID- 16295634
TI  - Study compares three teeth whitening techniques.

PMID- 16295635
TI  - Oral pathology quiz 815: radiopaque lesion in the maxillary sinus.

PMID- 16295636
TI  - UDM report: outstanding students; patient-centered practitioners.

PMID- 16295637
TI  - U-M report: progressing in research, technology and fundraising.

PMID- 16295638
TI  - 2005 Presidential Address. A purpose-driven profession.

PMID- 16295639
TI  - 2005 Remington Lecture. Life's lessons for a pharmacy family.

PMID- 16295640
TI  - 2005 Prescott Lecture. Advancing pharmacy through entrepreneurial leadership.

PMID- 16295641
TI  - Definition of medication therapy management: development of professionwide
      consensus.
AB  - OBJECTIVE: To describe events leading to development of a professionwide
      consensus definition of medication therapy management (MTM) and attendant
      programs and services and present the document (definition, services, and program
      requirements) resulting from the process. DATA SOURCES: Author's own knowledge
      and records of events. SUMMARY: Following the late 2003 passage of the Medicare
      Prescription Drug Improvement and Modernization Act, the pharmacy profession had
      a need to act quickly to define MTM so that a consensus definition would be
      available as regulations implementing the Medicare Part D benefit were being
      written. The American Pharmacists Association facilitated this process by
      convening a broad working group of members and other involved parties to draft a
      preliminary definition. The Pharmacy Practice Activity Classification was used to
      check elements of the definition for consistency with services being offered in a
      wide variety of settings. A professionwide stakeholders conference was then
      convened with representatives from each of 11 national pharmacy organizations.
      This group, following a daylong meeting in late May 2004 and several weeks of e
      mail messages and conference calls, finalized the MTM definition, which was then
      approved by the chief executive officers of all 11 groups. CONCLUSION: Through
      the extraordinary efforts of the numerous organizations and participants, the MTM
      Services Definition is one that is applicable within diverse pharmacy practice
      segments, whose services are feasible for a majority of practitioners to
      implement, and whose elements are supported by a profession-wide consortium of 11
      national professional pharmacy organizations. This historic achievement is the
      first step on a journey to find the best ways to effectively deliver MTM services
      to patients.

PMID- 16295642
TI  - Medication Therapy Management in community pharmacy practice: core elements of an
      MTM service (version 1.0).
AB  - OBJECTIVE: To develop a model framework of Medication Therapy Management (MTM) in
      community pharmacy designed to improve care, enhance communication among patients
      and providers, improve collaboration among providers, and optimize medication use
      that leads to improved patient outcomes. DATA SOURCES: Peer-reviewed literature,
      structured discussions with community pharmacy leaders and representatives from
      pharmacy benefit providers and health plans, and input from pharmacists and
      pharmacy associations. SUMMARY: Building on an MTM consensus definition adopted
      by 11 national pharmacy organizations in July 2004, this model describes core
      elements of an MTM service that can be provided by pharmacists across the
      spectrum of community pharmacy. The model is structured for pharmacists to use
      with all patients in need of MTM services, both in the private and public sector.
      The model describes five core elements of MTM in the community pharmacy setting:
      medication therapy review (MTR), a personal medication record (PMR), a medication
      action plan (MAP), intervention and referral, and documentation and follow-up.
      The MTR can be comprehensive or targeted, depending onthe needs of the patient.
      The PMR and MAP are patient-centered documents intended to be used by the patient
      to improve medication self-management. A collaborative approach to patient care
      involving patients, pharmacists, and physicians and other health care providers
      is advocated in the model. General patient eligibility considerations are also
      described. CONCLUSION: A model framework for consideration by community
      pharmacists in developing MTM services is described. The model consists of five
      core elements for MTM service delivery in community pharmacy practice.

PMID- 16295643
TI  - Medication therapy management services: a critical review.
AB  - OBJECTIVE: To identify and examine medication therapy management (MTM) practice
      and compensation models currently being used by public and private sector
      programs, develop a model for payers to consider in compensating pharmacists for
      the provision of MTM services, and review how a relative value-based payment
      system based upon Current Procedural Terminology (CPT) codes might apply to MTM
      services. DATA SOURCES: Peer-reviewed literature; study of existing MTM practice
      and compensation models; interviews with pharmacists, pharmacy benefit providers,
      health plans, and policy makers; structured discussions with industry experts.
      SUMMARY: Implementation of MTM represents an opportunity for pharmacists to
      provide public and private payers with examples of service packages and business
      models that improve patient therapeutic outcomes. MTM services can lead to
      overall cost reductions and improved health outcomes. Recommendations for
      pharmacists, health plans, and Medicare Part D prescription drug plan sponsors
      are provided. Pharmacists should standardize and package MTM services at varying
      levels of intensity; determine work values for MTM CPT codes, use standards for
      billing and service delivery, build supply capacity to meet demand for MTM
      services, and cultivate patient and provider support for pharmacist-provided MTM
      services. Plans and sponsors should develop mechanisms for measuring MTM impact
      on overall health care costs and develop payment systems to cover costs as well
      as sustain and provide for growth in the number of providers. CONCLUSION: The
      essential components of MTM business and payment models, as outlined in this
      article, can be effectively mapped to relative value-based CPT codes for
      pharmacist-provided MTM services. Pharmacy providers, after considering various
      factors and conditions in their own environment, can develop an optimal MTM
      service package and business model based on this information.

PMID- 16295644
TI  - Financial analysis of cardiovascular wellness program provided to self-insured
      company from pharmaceutical care provider's perspective.
AB  - OBJECTIVES: To perform a retrospective financial analysis on the implementation
      of a self-insured company's wellness program from the pharmaceutical care
      provider's perspective and conduct sensitivity analyses to estimate costs versus
      revenues for pharmacies without resident pharmacists, program implementation for
      a second employer, the second year of the program, and a range of pharmacist
      wages. DESIGN: Cost-benefit and sensitivity analyses. SETTING: Self-insured
      employer with headquarters in Canton, N.C. PATIENTS: 36 employees at facility in
      Clinton, Iowa. INTERVENTIONS: Pharmacist-provided cardiovascular wellness
      program. MAIN OUTCOME MEASURES: Costs and revenues collected from pharmacy
      records, including pharmacy purchasing records, billing records, and pharmacists'
      time estimates. METHODS: All costs and revenues were calculated for the
      development and first year of the intervention program. Costs included initial
      and follow-up screening supplies, office supplies, screening/group presentation
      time, service provision time, documentation/preparation time, travel expenses,
      claims submission time, and administrative fees. Revenues included initial
      screening revenues, follow-up screening revenues, group session revenues, and
      Heart Smart program revenues. RESULTS: For the development and first year of
      Heart Smart, net benefit to the pharmacy (revenues minus costs) amounted to
      dollars 2,413. All sensitivity analyses showed a net benefit. For pharmacies
      without a resident pharmacist, the net benefit was dollars 106; for Heart Smart
      in a second employer, the net benefit was dollars 6,024; for the second year, the
      projected net benefit was dollars 6,844; factoring in a lower pharmacist salary,
      the net benefit was dollars 2,905; and for a higher pharmacist salary, the net
      benefit was dollars 1,265. CONCLUSION: For the development and first year of
      Heart Smart, the revenues of the wellness program in a self-insured company
      outweighed the costs.

PMID- 16295645
TI  - Optimizing pharmacists' effectiveness as medication therapy managers through a
      segmentation approach.
AB  - OBJECTIVE: To determine whether older persons could be segmented into meaningful
      subgroups that shared similar patterns in terms of self-assessments of medication
      related knowledge, beliefs, and perceived abilities. DESIGN: Secondary analysis
      of data previously collected from a cross-sectional, descriptive study. SETTING:
      United States. PARTICIPANTS: A total of 500 community-dwelling older persons, 65
      years and older, using at least one prescription medication. INTERVENTION: Mail
      survey. MAIN OUTCOME MEASURES: Older persons' self-assessments of medication
      related knowledge, beliefs, and perceived abilities, as well as perceptions of
      pharmacist-patient relationships. RESULTS: The data set contained usable
      responses from 330 respondents out of 496 surveys presumably delivered (66.5%).
      Cluster analysis revealed three groups of older persons who showed differences in
      terms of medication-related beliefs and perceived abilities. Older persons in
      group 1 reported worse health, used the most prescription medications, sought the
      most advice from pharmacists, and had the lowest perceived abilities. Older
      persons in group 2 reported good health, took the fewest medications, sought
      pharmacists' advice least frequently, and had the lowest beliefs and high
      perceived abilities. Older persons in group 3 reported the best health, had the
      highest beliefs, high perceived abilities, and the highest perceptions of
      pharmacist participative behavior, patient-centeredness, relationship quality,
      and commitment. CONCLUSION: Pharmacists can use a segmentation approach to target
      those older persons who are most in need of medication therapy management.

PMID- 16295646
TI  - Patient evaluations of pharmacist performance with variations in attire and
      communication levels.
AB  - OBJECTIVE: To determine whether the attire of a pharmacist has any effect on how
      he is evaluated when a patient also considers the pharmacist's performance and to
      assess whether attire and performance interact to influence patients'
      evaluations. DESIGN: Randomized, cross-sectional, three-factor design. SETTING:
      Community pharmacy settings were portrayed. PARTICIPANTS: 179 university staff
      members. INTERVENTIONS: Videos of pharmacist-patient interactions were encoded
      and placed on a Web site to be viewed by participants. MAIN OUTCOME MEASURES:
      Service encounter satisfaction, perceptions of overall service quality, trust in
      the service provider, and behavioral intentions based on two levels of pharmacist
      communication performance (high or adequate), three levels of dress style
      (casual, business casual, formal), and two levels of white coat (wearing or not).
      RESULTS: Of the three independent variables, only communication performance was
      found to significantly influence the dependent variables. High communication
      performance resulted in higher satisfaction scores, higher perceptions of
      quality, higher levels of trust, and behavioral intention scores that reflected a
      greater willingness to use and recommend the pharmacist. CONCLUSION: Style of
      dress or whether the pharmacist was wearing a white coat did not significantly
      influence participants' evaluations of the pharmacist in this study. Rather, the
      level of the pharmacist's communication performance was the most important cue
      used by participants in their ratings of service encounter satisfaction,
      perceptions of overall service quality, and trust in the service provider.

PMID- 16295647
TI  - Sensitivity of over-the-counter pregnancy tests: comparison of utility and
      marketing messages.
AB  - OBJECTIVE: To determine the sensitivity of seven over-the-counter pregnancy tests
      (OTC-PTs) using urine containing a mixture of human chorionic gonadotropin (hCG)
      related molecules as found on the first day of missed menstrual period. DESIGN:
      Blinded in vitro sensitivity analysis. SETTING: Medical school laboratory.
      PARTICIPANTS: None. INTERVENTIONS: Urine was tested with OTC-PT devices at titers
      of 100, 50, 25, 12.5, 6.3, and 0 mIU/mL hCG immunoreactivity, and laboratory
      workers rated their confidence in the test result based on whether the test
      result was a clear, sharp, and unquestionable band in the test window. MAIN
      OUTCOME MEASURES: Analytical sensitivity, defined as the urine concentration at
      which all OTC-PTs tested gave a positive result regardless of operator confidence
      score; clinical sensitivity of OTC-PTs, defined as the proportion of pregnancies
      likely to be detected on the first day of a missed period and calculated from the
      analytical sensitivity and a recently published regression curve for total urine
      hCG immunoreactivity in 25 urine samples from this period of gestation;
      percentage of tested devices showing a band in the test window at a specific hCG
      concentration measured devices positive; percentage faulty devices, defined as
      the proportion of tested devices failing to yield a band in the control window;
      and confidence score, determined from operator ratings for each device at each
      concentration of hCG. RESULTS: First Response Early Result had an analytical
      sensitivity of 6.3 mIU/mL, which was estimated to detect greater than 95% of
      pregnancies on the day of missed period. The sensitivity of Clearblue Easy
      Earliest Results was 25 mIU/mL, which indicated detection of 80% of pregnancies.
      The sensitivity of the five other products was 100 mIU/mL or greater, indicating
      detection of 16% or less of pregnancies. Three of these last products included
      faulty devices. CONCLUSION: Universal claims for OTC-PTs of more than 99%
      laboratory accuracy and use as early as the first day of missed period, while
      cleared for use by the U.S. Food and Drug Administration, are ambiguous and
      inappropriate for many products, according to these data. The majority of
      products tested were found to detect only a small percentage of pregnancies on
      the first day of a missed menstrual period. Until more data become available on
      the actual clinical sensitivity of these products, pharmacists should advise
      consumers to be cautious in interpreting test results.

PMID- 16295649
TI  - Use of personal digital assistants to deliver education about adherence to
      antiretroviral medications.

PMID- 16295648
TI  - Retrospective detection of potential medication errors involving drugs with
      similar names.
AB  - OBJECTIVE: To estimate frequencies of potential errors involving similarly named
      drugs using a retrospective claims database and measure the association between
      frequencies of potential errors and two measures of drug name similarity, edit
      distance (minimum number of insertions, substitutions, or deletions of characters
      required to change a given word into another target word) and normalized edit
      distance (proportion of letters that must be changed to commute one word to
      another, and ranges from 0 to 1, with 0 indicating identical words, and 1
      indicating a pair of words with no common letters). DESIGN: Retrospective
      database analysis. SETTING: Idaho Medicaid claims data from 1993 to 2000.
      PATIENTS: Not applicable. INTERVENTION: Potential errors were detected using
      adjacent claims generated by dispensing of one drug followed by dispensing of the
      other drug with a similar name. In all, four potential error criteria were
      developed: two for detecting potential refill errors and two for detecting
      potential initial errors. A total of 10 drug pairs were randomly selected from
      the Idaho Medicaid claims database for each value of edit distance, which ranged
      from 1 to 30 (n = 300). MAIN OUTCOME MEASURES: Frequencies of potential
      medication errors in claims sequences for initial and refill claims, edit
      distance, and normalized edit distance. RESULTS: Of 300 drug pairs studied, 106
      (35.33%) were involved in at least one potential error. A total of 1,138
      dispensing episodes satisfied the criteria for potential errors. Frequencies of
      potential errors per drug pair were negatively associated with edit distance (r =
      -0.133, P < .05) and normalized edit distance (r = -0.226, P < .01). Frequencies
      of potential initial errors also were negatively associated with edit distance (r
      = -0.126, P < .05) and normalized edit distance (r = -0.222, P < .01). Potential
      refill errors also had negative association with edit distance (r = -0.134, P <
      .05) and normalized edit distance (r = -0.226, P < .01). CONCLUSION: Error
      criteria were successfully applied to a retrospective claims database to detect
      potential initial and refill errors that involved similarly named drugs.

PMID- 16295650
TI  - James Hartley Beal (1861-1945): educator-statesman.

PMID- 16295651
TI  - Avian influenza poses threat.

PMID- 16295652
TI  - New drugs: tigecycline, ziconotide, and clofarabine.

PMID- 16295653
TI  - OTC product: BD Ultra-Fine 33 Lancets.

PMID- 16295655
TI  - The use of bacteriophages in eliminating polyresistant strains of Staphylococcus
      aureus and Streptococcus agalactiae.
AB  - Temperate bacteriophages were induced in and released from isolates of
      Staphylococcus aureus and Streptococcus agalactiae using mitomycin C. Various
      specific indicator cultures were tested for providing clear plaques after phage
      infection. Specific lytic mixture of bacteriophages was prepared using the
      induced, modified and laboratory variants of phages. Under laboratory conditions,
      the mixture eliminated all isolates from the tested collection of microorganisms.
      The restriction barrier of some bacterial isolates to bacteriophage infection was
      overcome either by UV irradiation or in vitro modification of bacteriophage DNA
      with specific methyltransferases. Conjugative R plasmids, capable of replication
      in G+ and G- bacteria, were detected and isolated from S. aureus and S.
      agalactiae antibiotic-resistant strains.

PMID- 16295656
TI  - 1-Aryl-5-benzylsulfanyltetrazoles, a new group of antimycobacterial compounds
      against potentially pathogenic strains.
AB  - A set of 21 1-phenyl-5-benzylsulfanyltetrazoles substituted on the phenyl ring as
      well as on the benzyl moiety was evaluated for in vitro antimycobacterial
      activity against Mycobacterium avium and two strains of M. kansasii. We tried to
      use the Hansch approach, the Free-Wilson approach and their combination for
      structure-activity correlation but the calculations were statistically
      insignificant.

PMID- 16295657
TI  - Oligosaccharides produced by submerged cultures of Claviceps africana and
      Claviceps sorghi.
AB  - Oligosaccharides produced by submerged cultures of C. africana and C. sorghi were
      isolated by semipreparative HPLC. Structure of 6-O-beta-D-fructofuranosyl-D
      glucopyranose (blastose), 1,6-bis-O-(beta-D-fructofuranosyl)-alpha-D
      glucopyranoside (neokestose) and two sugar alcohols, 1-O-beta-D-fructofuranosyl-D
      mannitol (fructosylmannitol) and 1,6-bis-O-(beta-D-fructofuranosyl)-D-mannitol
      (bisfructosylmannitol) was determined by NMR spectrometry. MALDI TOF MS analysis
      revealed molecular ions [M+Na]+ that indicate the presence of other tetra- and
      pentasaccharides (m/z = 689.4 and 851.5, respectively) and corresponding sugar
      alcohol (m/z = 691.4). Rapid conversion of sucrose into series of
      oligosaccharides and corresponding sugar alcohols was observed in all tested
      strains.

PMID- 16295654
TI  - Role of the leukemia-inhibitory factor gene mutations in infertile women: the
      embryo-endometrial cytokine cross talk during implantation--a delicate
      homeostatic equilibrium.
AB  - Locally secreted cytokines of both the embryonic and the endometrial origin
      control the implantation process. The defects in their signaling that lead to
      unfavorable environment within the uterus may cause embryo implantation failure.
      The leukemia inhibitory factor (LIF), interleukin-11 (IL-11) as well as IL-12/IL
      15/IL-18 system are regarded to be important signaling vectors. LIF plays an
      essential role in the preimplantation embryo development and the blastocyst
      implantation and its gene mutations in women contribute to the implantation
      failure and subsequent infertility. IL-11 signaling has been shown to be required
      for the uterine decidualization response as well as for the hatching and
      attachment of blastocysts. The IL-12/IL-15/IL-18 system interacts with
      endometrial leukocytes, particularly with NK cells, and influences directly the
      local angiogenesis and tissue remodeling. Differences in the levels of
      endometrial leukocytic subpopulations and in the patterns of intra-uterine
      cytokine concentrations that are observed between fertile and infertile women
      contribute to infertility probably by affecting the embryonic maternal dialogue
      during the implantation and early placentation period. Focusing on this cross
      talk promises to open new era in assisted reproduction techniques that will be
      based on diagnostics of missing signaling molecules and impairments of uterine
      receptivity as well as on therapeutic applications of individualized embryo
      culture and transfer media.

PMID- 16295658
TI  - Endosymbiotic alga from green hydra under the influence of cinoxacin.
AB  - Cinoxacin (Cxn) showed a strong effect on the endosymbiotic alga Chlorella; it
      was significantly damaged. Changes in algal color, position, structure and
      ultrastructure were found. In some algal cells ultrastructures were completely
      destroyed. The antichloroplastal and antimitochondrial effect was especially
      expressed. Damage to the thylakoid system of chloroplasts was more pronounced
      with increasing Cxn concentration. Some of the mitochondria were swollen and some
      of them were completely destroyed. From the evolutionary point of view, the
      correlation between antibacterial, and antichloroplastal and antimitochondrial
      effect of Cxn points to the evolutionary connection of chloroplasts and
      mitochondria with eubacteria.

PMID- 16295659
TI  - Enterobacter cloacae, an obligatory endophyte of pollen grains of Mediterranean
      pines.
AB  - Enterobacter cloacae was found to be associated with the pollen of several
      Mediterranean pines. The bacterium was detected only in mature pollen of Pinus
      halepensis, P. brutia, and P. pinea. E. cloacae is considered to be an obligatory
      endophyte based on its occurrence in disinfected male cones and the successful
      inoculation of seedlings of the above 3 species with E. cloacae AS1 isolated from
      pollen of P. halepensis used as a model strain. Strain AS1 was able to produce
      indolyl-3-acetic acid (IAA) from L-tryptophan in culture, and this was probably
      the source of the increased IAA content in the germination medium of pollen. In
      addition, strain AS1 promoted adventitious root formation in mung bean (Vigna
      radiata) cuttings. However, it was not possible to obtain bacterium-free pollen
      to elucidate its role in pollen germination.

PMID- 16295660
TI  - Reliability of diagnostic techniques for Erwinia amylovora, the causative agent
      of fire blight disease.
AB  - A total of 20 putative strains of Erwinia amylovora originating from 11 samples
      of host plants with symptoms of fire blight were analyzed in detail using
      commercial polyclonal antibodies in immunochemical tests. Fourteen strains
      reacted negatively in all tests; 6 strains reacted positively with a polyclonal
      antibody for PTA-ELISA (plate-trapped antigen-enzyme linked immunosorbent assay)
      at a concentration corresponding to A620 = 0.1, while at A620 readings of 0.01
      and 0.001 the results were negative. Five strains reacted positively with a
      polyclonal antibody for indirect immunofluorescence test at all tested
      concentrations. Three of those strains were positive in the PCR test with AMSbL
      and AMSbR primers designed for detection of E. amylovora. In hypersensitivity
      test in tobacco and in immature pear fruit assay, all putative strains were
      negative while a known reference strain of E. amylovora gave a typical
      hypersensitive-reaction response. On a medium with 5% sucrose the reference
      strain of E. amylovora produced levan while putative strains did not. After
      modification of the PCR protocol, 3 putative strains reacted as negatives.
      Optimization of PCR test was achieved by finding the optimum annealing
      temperature and time for primers. The recommended annealing temperature (49
      degrees C) for these primers was increased to 55 degrees C and the annealing time
      was reduced from 2 min to 30 s. Using the microbial identification system Biolog
      those 3 strains were identified as Pantoea dispersa (1 strain) and Pantoea
      agglomerans (2 strains). The strains are supposed to be white variants of the
      species P. dispersa and P. agglomerans occurring less frequently than the yellow
      variants. Since there were positive reactions in our immunochemical tests these
      strains could cause false positives in routine screening of plant samples.

PMID- 16295661
TI  - Ribotyping of Lactobacillus casei group strains isolated from dairy products.
AB  - A series of lactobacilli isolated from dairy products were characterized using
      biotyping and ribotyping with EcoRI and HindIII restriction enzymes. Biotyping
      assigned 14 strains as Lactobacillus casei, 6 strains as Lactobacillus paracasei
      subsp. paracasei and 12 as Lactobacillus rhamnosus. The obtained ribotype
      patterns separated all analyzed strains into two clearly distinguished groups
      corresponding to L. rhamnosus and L. casei/L. paracasei subsp. paracasei. The
      HindIII ribotypes of individual strains representing these two groups were
      visually very similar. In contrast, EcoRI ribotyping revealed high intraspecies
      variability. All ribotypes of L. casei and L. paracasei subsp. paracasei dairy
      strains were very close and some strains even shared identical ribotype profiles.
      The type strains L. casei CCM 7088T (= ATCC 393T) and Lactobacillus zeae CCM
      7069T revealing similar ribopatterns formed a separate subcluster using both
      restriction enzymes. In contrast, the ribotype profile of L. casei CCM 7089 (=
      ATCC 334) was very close to ribopatterns obtained from the dairy strains. These
      results support synonymy of L. casei and L. paracasei species revealed by other
      studies as well as reclassification of the type strain L. casei CCM 7088T as L.
      zeae and designation of L. casei CCM 7089 as the neotype strain.

PMID- 16295663
TI  - Process-independent quantitative assessment of residual biological contamination
      of medical devices reprocessed in washer-disinfectors.
AB  - A method based on measuring a soil-induced fluorescence intensity response of 1,8
      anilinonaphthalene sulfonate at two fixed wavelengths (460 and 510 nm) was used
      for determining residual contamination on test soil carriers simulating medical
      devices after passage through a hospital washer-disinfector. The fluorescence
      response can be satisfactorily calibrated to soil levels as low as approximately
      1 microg/L. Practical tests were performed in two hospitals with washer
      disinfectors of 3 types and with several chemical or enzymic cleansers
      disinfectants. In combination with the previously developed system of
      standardized test soil carriers simulating both easily and poorly accessible
      parts of soiled medical devices, the liver-lactose-oil test soil and an efficient
      sonication procedure for stripping the residual soil off the carriers, this soil
      detection method permits the detection of very low contamination levels.

PMID- 16295662
TI  - Lectin-binding characteristics of a Lyme borreliosis spirochete Borrelia
      burgdorferi sensu stricto.
AB  - Borrelial glycoconjugates were localized by labeled lectins on ultrathin
      cryosections and on surfaces of intact negatively stained bacteria. Protein
      saccharide complexes in these glycoconjugates were partially characterized by
      means of enzyme deglycosylation and mild alkali pretreatment of cryosections. The
      results of labeling were examined by transmission electron microscopy.
      Statistically evaluated results (relative labeling index, chi2 test) of gold
      labeling indicated that surfaces of Borrelia burgdorferi strain B31 and external
      (outer) membrane vesicles (MVs) were covered with glycoconjugates containing O
      glycosidically linked N-acetyl-D-galactosamine (GalNAc) and N-glycosidically
      linked N-acetyl-D-glucosamine (GlcNAc). The presence of N-linked GalNAc, sialic
      acid, mannose and fucose on the surfaces of outer membranes and MVs was probably
      due to an adherence of BSK-H medium components, especially rabbit serum, to
      Borrelia surfaces.

PMID- 16295664
TI  - Intratracheal and intranasal immunization with ovalbumin conjugated with Bacillus
      firmus as a carrier in mice.
AB  - Inactivated Bacillus firmus (BF), G+ nonpathogenic bacterium of the external
      environment, was coupled to ovalbumin (OVA) and used in immunization experiments
      as antigen carrier. Balb/c mice were immunized thrice intra-tracheally and intra
      nasally with conjugates of OVA and BF. Surprisingly, administration of OVA-BF
      conjugates inhibited anti-OVA IgG response in both sera and mucosal secretions if
      compared to an exposure to OVA alone. The suppression of antigen-specific
      antibody production was accompanied by promotion of TH1 phenotype.

PMID- 16295665
TI  - Diabetes mellitus and candidiases.
AB  - Patients in various clinical states of diabetes mellitus (according to the
      recommendation of the American Diabetes Association) as a primary diagnosis were
      examined for fungal infections by Candida species. Candida spp. were detected in
      urine, in the material taken from the mouth cavity, nails, skin lesions, ears and
      eyes, by cultivation on the Sabouraud agar, CHROMagar Candida, and by saccharide
      assimilation. In the group of diabetics with symptoms of oral candidiasis and
      denture stomatitis C. albicans was identified in 8 cases, C. tropicalis in 3, C.
      parapsilosis in 2; 1 strain of C. guilliermondii was also isolated. In patients
      with urinary tract infections the presence of C. albicans was shown in 12 cases;
      C. parapsilosis was detected in 6 cases and two strains of each C. tropicalis and
      C. krusei were also isolated. In patients with leg ulcers C. albicans (25 cases),
      C. parapsilosis (5), C. tropicalis (3) and one strain of each C. krusei and C.
      robusta were isolated. Otomycosis was associated with one strain of C. albicans,
      C. parapsilosis, C. tropicalis and C. guilliermondii. C. albicans was most
      frequently associated with onychomycosis, paronychia and endophthalmitis; C.
      parapsilosis was the second most rated yeast.

PMID- 16295668
TI  - Survival pattern of reported HIV infected individuals in the city of Delhi
      (India).
AB  - There is very little data on the survival period of HIV in India. In this paper
      survival experience of 836 HIV infected patients was studied whose illness was
      diagnosed upto Dec. 2003. On analysis, it was observed that the mortality was
      maximum in the age-group of 41-50 years (25%), 24.4% in males and 24.2% in
      females. For patients with tuberculosis morality was 23% and was higher among
      those with unsafe sex (24.5%) as a risk factor. Mortality of AIDS patients in
      Delhi decreased from 63.2% in 1994 to 24.2% in the year 2003. Also tuberculosis
      was found to be the major opportunistic infection affecting 83.2% of the
      patients. An increasing trend was observed with tuberculosis from 84.2% in 1994
      to 89.1% in 1997 (p<0.05), but overall tendency was around 84% during the period
      1994 to 2003. In AIDS related symptoms chronic diarrheoa accounted for only 5.2%.
      The median length of survival of HIV infected patients with all subjects was 75
      months. The hazard rate showed an increasing trend and reached its peak at 102
      months. The survival of HIV infected patients in Delhi was found to be shorter
      than that of patients in developed countries and developing African countries.

PMID- 16295666
TI  - Detection of Candida albicans by culture, serology and PCR in clinical specimens
      from patients with ulcerative colitis: re-evaluation of an old hypothesis with a
      new perspective.
AB  - The relationship between inflammatory bowel disease and microorganisms was
      evaluated. The presence of Candida albicans-specific IgM and IgG antibodies in
      serum samples and the presence of C. albicans in stool and colonal mucosa samples
      of the patients did not exhibit any significant difference between 21 patients in
      active stage and 15 patients in remission of ulcerative colitis (UC) (compared
      with 19 control patients). The invasion of yeast cells to the colonal mucosa was
      demonstrated by detecting C. albicans DNA using specific PCon1, PCon2, and PspA2
      primers in PCR assay. Eighteen of 36 patients (50%) were found to be DNA positive
      while in 19 controls only 4 (21%) were found to be positive. The presence of DNA
      in the association of the positive serological reactivity is suggested as an
      important diagnostic marker of UC.

PMID- 16295667
TI  - Yersinia Yop-specific IgA antibodies in Hungarian blood donors.
AB  - Sera of 112 healthy Hungarian blood donors were tested for the presence of
      Yersinia enterocolitica and Y. pseudotuberculosis-specific agglutinins by tube
      agglutination, and for that of yersinia outer membrane protein (Yop)-specific IgA
      antibodies by ELISA. The positive results of this latter assay were confirmed by
      immunoblot. Only one sample gave a positive agglutination reaction with Y.
      enterocolitica antigen (group 03) and four exhibited an equivocal reaction with
      Y. pseudotuberculosis antigens (groups II and IV). Contrary to the low incidence
      of agglutinins, 15.1% of the samples showed a positive Yop-specific IgA reaction,
      while further 5.3% samples fell into the equivocal range by ELISA (17 and 6
      specimens, respectively). Eleven of these samples (9.8% of all specimens tested)
      were also positive by immunoblot for the presence of Yop-specific IgA antibodies.
      These data suggest a higher incidence of yersinia infections than the 1.0-1.4 per
      10(5) population predicted on the basis of stool culture results.

PMID- 16295669
TI  - Prevalence and determinants of reproductive tract infections among women.
AB  - Reproductive tract infections (RTIs) are one of the most common health problems
      in women during reproductive age. There are gaps in the knowledge regarding the
      prevalence and determinants of these infections among women. A cross-sectional
      study was conducted at Primary Health Centre, Palam. Three hundred currently
      married women from antenatal and gynae clinic were interviewed followed by
      clinical examination and microbiological investigations. The prevalence of RTIs
      was 37.0 % based on symptoms and 36.7 % by laboratory investigations, including
      26.3% candidiasis, 18.0% vaginitis, 15.7% trichomoniasis and 14.3% bacterial
      vaginosis. Factors which were found to be significantly associated with
      reproductive tract infections in women were not cleaning genitals daily, last
      delivery being domiciliary, history of anal intercourse, last delivery conducted
      by dai, relative/neighbour, not bathing daily, not bathing daily during
      menstruation and history of abortions. Strength of association of these factors
      was further analysed using the odd ratio with 95% confidence interval.

PMID- 16295670
TI  - Laboratory bio-assay of temephos and fenthion against some vector species of
      public health importance.
AB  - Laboratory studies carried out using Temephos and Fenthion, two commonly used
      larvicides under Urban Malaria Scheme (NMEP) and NFCP for the control of mosquito
      larvae. The results revealed that the LC50 and LC90 values for temephos against
      Aedes aegypti 0.0177 and 0.0559, Anopheles stephensi 0.0148 and 0.0472, Culex
      quinquefasciatus 0.0157 & 0.0480 and for Culex vishnui group of mosquitoes 0.043
      & 0.0118 ppm respectively. The results obtained revealed that there is a 62.8 &
      94.12 times increase in the LC50 & LC90 of Cx. Quinquefasciatus which indicates
      that the species has developed resistance to temephos. There were 6.32 & 8.34
      fold increase in Ae. aegypti and 2.27 & 2.34 fold increase in LC50 & LC90 values
      of An. stephensi are indicative of development of tolerance against temephos.
      Similarly LC50 and LC90 values estimated for fenthion against Ae. aegypti 0.0173
      & 0.0392, An. stephensi 0.0274 & 0.0992 and Cx. quinquefasciatus 0.03 & 0.0469
      respectively. The slope values were found to be higher in fenthion as compared to
      temephos. It was recorded to be 2.72 times higher in Cx. quinquefasciatus and
      1.54 times against An. stephensi. However, much difference was not observed in
      the slope values of temephos and fenthion in Ae. aegypti.

PMID- 16295671
TI  - Predatory potential of Nepa cinerea against mosquito larvae in laboratory
      conditions.
AB  - Biocontrol potential of nepidae bug, Nepa cinerea against immature stages of
      Anopheles stephensi, Anopheles culicifacies, Culex quinquefasciatus and Aedes
      aegypti was studied under laboratory conditions. It was found that N. cinerea had
      the highest predation against An. stephensi followed by An. culicifacies, Cmx
      quinquefasciatus and Ae. aegypti. From the analysis, it was found that N. cinerea
      has good predation efficacy. It can be used as a biological control agent to
      control of mosquito breeding in integrated disease vector control programme.

PMID- 16295672
TI  - Helminthic infestation of the primary school-going children in Manipur.
AB  - A total of 1010 stool samples collected from the primary school-going children
      between the age group of 5 to 10 years from September 1998 to October 2000, were
      studied to find out the prevalence of intestinal helminths in this paediatric age
      group and in the urban and rural areas of Manipur. The samples were processed in
      the Microbiology Department, RIMS, Imphal by wet film, iodine preparation and
      concentration techniques (formol-ether concentration) to find out the presence of
      eggs, larvae of the intestinal parasites (helminths). A total of 248 (24.5%) were
      positive for various helminths. Among the positive cases, 110 (26.3%) were from
      the urban area (city) and 138 (23.4%) from the rural areas of Manipur. Of the 552
      males and 458 females tested, 136 (24.6%) males and 112 (24.5%) females
      respectively were positive for various helminths. Maximum number of parasitic
      infection occurred in the age group of 5 to 6 years (27.0%) in both sexes. Among
      the parasites, Ascaris lumbricoides was the commonest (19.6%) followed by
      Trichuris trichiura (2.18%), Hymenolepis nana (0.99%), Tapeworm (0.19%), Hookworm
      (0.09%), Strongyloides stercoralis (0.09%), Enterobius vermicularis (0.09%).
      Mixed infection of Ascaris lumbricoides with T. trichiura (1.08), T. trichiura
      with E. vermicularis (0.09%) and T. trichiura with S. stercoralis (0.09) were
      also encountered. Antihelminthic drugs were prescribed to those who were found
      positive for the helminths.

PMID- 16295673
TI  - Kala-Azar at high altitude.
AB  - Kala-azar or Visceral leishmaniasis (VL) is a disease of low altitude
      (approximately 500 meters mean sea level). In India, however cases have been
      reported from sub-Himalayan region (350-960 meters MSL) of Kumaon region of
      Uttaranchal. We present two patients of VL, natives of tribal district of
      Kinnnaur (2000-3000 meters MSL), Himachal Pradesh, who had never visited known
      endemic area for Leishmaniasis. These are probably first indigenous cases of VL
      being reported from an area situated at an altitude of 3000 meters and 2300
      meters MSL.

PMID- 16295674
TI  - A study of ocular infections amongst primary school children in Delhi.
AB  - The present study of ocular infections was conducted amongst primary school
      children residing in an urban slum and rural area of Delhi. A total of four
      schools were selected, two from urban slum in Central Delhi Rouse Avenue and two
      from a peripheral village on the outskirts of Delhi. All the children studying in
      the above mentioned schools and residing in the same area were covered. All the
      study subjects were interviewed, clinically examined and given a proforma to be
      filled by their parents. Of the total 775 subjects only 91 (11.74%) had ocular
      infections. Conjunctivitis was the most prevalent infection followed by trachoma,
      stye, blepharitis and chalazion. The type and prevalence of infection was
      similar, in both sexes and both areas, rural and urban. There was a significant
      rising trend of ocular infection with increase in age. A significant association
      was found between ocular infections and religion but the association with per
      capita income was not significant.

PMID- 16295675
TI  - Latex agglutination test in the diagnosis of pyogenic meningitis.
AB  - Samples of cerebrospinal fluid (n=204) from pediatric patients with clinically
      suspected pyogenic meningitis were examined by direct microscopy, bacterial
      culture and Latex Agglutination Test (LAT). Latex Agglutination Test was done for
      detection of antigen of Streptococcus pneumoniae and Haemophilus influenzae type
      b. Among 38 LAT positive cases, culture and/or gram stain was positive in only 20
      cases and 18 cases were detected exclusively by LAT. Besides, LAT was useful in
      detecting the pre-treated cases as 11 out of 55 samples from pre-treated cases
      were positive by LAT in comparison to culture and/or Gram stain which detected
      only 4 of 55 cases. LAT is simple, rapid and more reliable test.

PMID- 16295676
TI  - Seroprevalence of anti Helicobacter pylori IgG/IgA in asymptomatic population
      from Delhi.
AB  - Helicobacter pylori is recognised as the most important etiological agent for
      chronic antral gastritis in humans, the major predisposing factor in the
      pathogenesis of duodenal and gastric ulcers as well as probable cofactor in the
      development of gastric cancer. This study was undertaken to determine the
      seroprevalence of anti - H. pylori IgG/ IgA in asymptomatic population. Two
      hundred and fifty eight serum samples from various age groups (1-40 years) were
      collected from patients admitted to the wards for conditions other than
      gastrointestinal disorders and screened for anti H. pylori IgG/IgA antibodies.
      The prevalence of anti H. pylori IgG/IgA in the age group < 10 years, 10-19
      years, 20-29 years, 30-39 years and anti 40 years were found to be 38.89%,
      52.08%, 59.62%, 67.88% and 54.17% respectively. The prevalence of H. pylori
      increased markedly with age, being maximum in 30-39 year age group. Similar trend
      was observed in a study conducted in South India and Mumbai. Almost half the
      children acquire H. pylori infection early in life which increases slowly and
      steadily with a peak prevalence in the age group 30-39 years and then declines as
      the age advances. There was no significant difference in prevalence rate in males
      and females.

PMID- 16295677
TI  - Surveillance of dengue vector at thiruvananthapuram (Kerala) International
      Airport.
AB  - A survey of Aedes (Stegomyia) mosquitoes was undertaken in and around the
      International airport at Thiruvananthapuram during premonsoon season. An attempt
      has been made in this paper to elaborate on the presence of risk potential for
      Dengue /yellow fever at the airport with the detection of Aedes breeding. The
      entomological indices have also been discussed with regard to presence of
      potential wet containers and rate of infestation by Aedes mosquitoes. The airport
      area was searched for Aedes (Stegomyia) breeding where 20% of the premises were
      found positive for Aedes aegypti breeding and one premise (6.6%) was found
      positive with Aedes albopictus breeding. In the 400 meters (perimeter) of
      airport, four municipal wards namely Chakka, Sankumugam, Valiyathura and
      Vettucadu were surveyed. The house index ranged from 5.8% to 11.7% for Aedes
      aegypti while, it was between 9.8% to 19.2% with regard to Aedes albopictus. The
      container index ranged between 4.4% to 9.9% for Aedes aegypti and 7.1% to 15.3%
      for Aedes albopictus. Breteau index was found to be between 23.5% to 51.9% for
      both the species. The susceptibility test conducted against different
      insecticides showed that the immature stages of Ae. aegypti and Ae. albopictus
      were found to be susceptible to the commonly used larvicides in public health
      viz. Temephos (0.02 ppm), Fenthion (0.05 ppm), Malathion (1.0 ppm) and
      Fenitrothion (0.06 ppm).

PMID- 16295678
TI  - Bacteriological and parasitological study of puffed rice.

PMID- 16295679
TI  - Bacteriological profile and changing antibiograms of Vibrio cholerae isolated in
      east Delhi, 1998-2003.

PMID- 16295680
TI  - Syndromic management of vaginal discharge and pelvic inflammatory disease among
      women in a rural community of Haryana, India: agreement of symptoms enquiry with
      clinical diagnosis.
AB  - World Health Organisation (1984) advocated syndromic approach for management of
      reproductive tract infections/sexually transmitted diseases. Some investigators
      have cautioned against using this approach to diagnose and treat vaginal
      discharge and pelvic inflammatory disease. The prevalence of RTIs in rural areas
      of Haryana is high and availability of per-speculum examination facility is
      scarce. The scope for laboratory diagnosis of RTI in rural areas is remote in
      near future. A community-based study was conducted to assess the agreement of
      symptoms enquiry with the syndromic diagnosis of RTIs/STDs (based upon per
      speculum examination). A total of 812 women were interviewed by ANMs and were
      examined by a lady doctor. History based ANM's diagnosis was found to be having
      high sensitivity (80.5%) and high positive predictive value (81.3%). However it
      had low specificity (48.6%) and low negative predictive value (47.5%) compared to
      clinical diagnosis. Level of agreement was found to be fair (Kappa = 0.28, 95% CI
      = 0.20-0.36). The chances of over treatment for vaginal discharge and pelvic
      inflammatory disease were only 16% and 15% respectively. However, history based
      syndromic protocols need revision. Proposed protocol is discussed in this paper.

PMID- 16295681
TI  - A study of HIV/STD infections amongst commercial sex workers in Kolkata. (India)
      Part-IV laboratory investigation of STD and HIV infections.
AB  - Out of 867 sex workers examined during 1998-2000 from the five important red
      light areas of Kolkata, 26.18%(227) were suffering from active syphilitic
      infection having positive VDRL test with titre 1/8 and above. Vaginal smear for
      gram staining was collected from all sex workers, and found positive for active
      gonorrhoeal infection in 41.8% (362). Culture positivity for gonorrheal infection
      was 34.14% (296). Sex workers were also having other STD infection, 23.64% (205)
      Trichomonas infection, 13.26% (115) Candidiasis, 8.77% (76), Gardenella and 3.0%
      (26) Chanchroid for which vaginal samples were found positive. HIV sero
      positivity was found to be 13.2% (115) out of 867 blood samples examined from all
      sex workers under study. There were 0.34% (3) sex workers who were also positive
      for HIV II infection along with HIV-I infection. A case of HIV II alone was not
      detected in any of the sex workers. Around 49.6% (430) knew that STD/HIV can be
      prevented by use of condom. However, condom was used by only 6.57% (57) sex
      workers.

PMID- 16295682
TI  - Antimicrobial susceptibility pattern and prevalence of extended spectrum beta
      lactamase (ESBLs) producing strains of Klebsiella pneumoniae from a major
      hospital in New Delhi.
AB  - Extended spectrum beta-lactamases (ESBLs) are plasmid mediated enzymes capable of
      hydrolyzing penicillins, broad spectrum-cephalosporins and monobactams. The ESBL
      producing K. pneumoniae strains are being reported from around the world
      including India. The present study was taken up to evaluate the ESBL production
      and in-vitro susceptibility of K. pneumoniae isolates from a hospital. The
      bacterial isolates collected during 2003 included 51 K. pneumoniae biochemically
      confirmed isolates from 395 patients admitted in various wards of a major
      hospital in New Delhi. The isolates were from pus, wound, pleural fluid, urine
      and tracheal aspirate of patients attending respiratory, urology and burns wards.
      Antimicrobial susceptibility was carried out by Kirby Bauer's disc diffusion
      technique using NCCLS criteria. A screening of ESBL production was done by Double
      disc synergy test (DDST) and using E-test ESBL strips. The frequency of
      resistance among K. pneumoniae for the cephalosporins (cefoxitin, cefuroxime,
      cefotaxime, ceftazidime, and cefepime) and non-cephalosporins (aztreonam,
      piperacillin, chloramphenicol and trimethoprim-sulfamethoxazole) were in the
      range of 39.2-88.0% and 51.0-90.2% respectively. 14 different antimicrobial
      resistance profiles were recognized ranging from resistance to only four (n=6,
      11.7%) to as many as ten (n=9, 17.7%). Among the 51 isolates of K. pneumoniae
      strains, a total of 36 (70.6%) could be identified as ESBL producers, that
      correlates with the high frequency of multi-drug resistant K. pneumoniae The
      study shows alarming rise in ESBL production among K. pneumoniae strains and high
      rate of resistance to a wide range of cephalosporin and non-cephalosporin group
      of antimicrobials.

PMID- 16295683
TI  - Significance and characterisation of pseudomonads from urinary tract specimens.
AB  - Pseudomonads are commonly encountered in clinical samples. Usually ignored as
      contaminants, these organisms are known to cause nosocomial opportunistic
      infections like urinary tract infections (UTI). One hundred and two pseudomonads
      obtained in pure culture and significant numbers from 8400 consecutive urinary
      tract (UT) specimens were biochemically characterised upto species level by a
      battery of biochemical tests. Modified Stoke's disk diffusion method was followed
      for testing antibiotic susceptibility. Beta-lactamase production was checked by
      nitrocefin disk method. Minimum Inhibitory Concentration for some of these
      strains against imipenem was done by agar dilution method of NCCLS. Etiological
      significance of isolating these organisms from UT specimens was also assessed. P.
      aeruginosa was the commonest (76) followed by B. pickettii (10), P. putida (6),
      P.fluorescence (2), P. stutzeri (20) P. vesicularis (2), S. putrefaciens (2) and
      Stenotrophomonas maltophilia (2). Seventy six per cent of P. aeruginosa produced
      beta-lactamases as compared to 45% of other pseudomonads. The frequency of
      antibiotic resistance was gentamicin and ciprofloxacin (68.6%) followed by
      netilmicin (60.7%), ceftazidime (58.8%), amikacin (43.1%) and piperacillin
      (39.2%). In 42 patients (51.2%) the etiological significance of isolating a
      pseudomonad could be confirmed. Risk factors for development of UTI were present
      in 62(75%). Obstructive uropathy (20) followed by post operative period and
      surgery on urinary tract were the commonest risk factors involved. A high level
      of resistance was observed for imipenem (P. aeruginosa 43.7% and other
      pseudomonads 25%).

PMID- 16295684
TI  - Morphotaxonomic studies to identify the members of the Anopheles subpictus Grassi
      (Diptera: Culicidae) species complex in riverine villages of District Sonepat,
      Haryana State, India.
AB  - Anopheles subpictus was reported to be a complex of four sibling species
      provisionally designated as species A, B, C and D. Present studies in District
      Sonepat, Haryana have revealed the sympatricity of species A, C and D based on
      the reported distinct morphotaxanomical identification characters in different
      life stages of the mosquito. Studies on field collected adult mosquitoes and
      isofemale progeny did not show variations in the prevalence of sibling species
      and also showed a possibility of use of a single reported morphological character
      in a given life stage for the identification of the members of this complex.

PMID- 16295685
TI  - Susceptibility of Phlebotomus argentipes against DDT in endemic Districts of
      North Bihar, India.
AB  - Susceptibility status of Indian kala-azar vector Phlebotomus argentipes after DDT
      spray from endemic areas of Muzaffarpur and Vaishali district and unsprayed non
      endemic area of Patna district, Bihar, India were compared. Higher Lc50 viz. 2.6%
      and 3.2% and LT50, values 51.0 and 69.0 minutes to 4% DDT were observed for P.
      argentipes of Muzaffarpur and Vaishali district, whereas P. argentipes of Patna
      district was 100% susceptible to same concentration, indicating increased
      tolerance in P. argentipes. It is concluded DDT resistant P. argentipes,
      particularly in endemic zone growing. The possible explanation could be long-term
      insecticidal pressure.

PMID- 16295686
TI  - Prevalence of HIV infection and AIDS symptomatology in malnourished children--a
      hospital based study.
AB  - One hundred and seventy five malnourished children aged between 1(1/2) and 12
      years attending pediatric department of Regional Institute of Medical Sciences
      Hospital, Imphal from January 2001 to June 2002 were screened for human
      immunodeficiency virus (HIV) infection along with their biological mothers after
      pretest counselling and informed consent. The prevalence rate of HIV
      seropositivity among malnourished children was 21.7%. Children aged between
      1(1/2) and 3 years had the highest seroprevalence (47.4%) and male to female
      ratio was 1.5: 1. Underweight children showed the highest seroprevalence (47.4%)
      and children with kwashiorkor showed least seroprevalence (10.5%). Mode of HIV
      transmission was vertical in 94.7%. The causative agent was HIV-I in all the
      cases. AIDS defining children features were seen more frequently among HIV
      seropositive malnourished children as compared to the seronegative children.
      Prolonged fever (p 0.001), oropharyngeal candidiasis (p<0.001), generalised
      lymphadenopathy (p<0.001) and disseminated maculopapular dermatitis (p<0.001)
      were significantly related to HIV infection. Among seronegative children 18.2%
      fulfilled the clinical criteria for AIDS and among seropositive children 94.7%
      had AIDS. The total mortality encountered among seropositive children was 34.2%.
      It is suggested to confirm findings based on larger community based data before
      recommending mandatory HIV testing in all malnourished children. Specific
      guidelines on the nutritional management of children with HIV/AIDS is needed in
      Manipur where HIV is spreading rapidly.

PMID- 16295687
TI  - A status survey of common water-borne diseases in desert city Bikaner (NW
      Rajasthan, India).
AB  - Water is scarce and, in general, a low quality resource in desert areas and the
      Indian desert is no exception. With this in view, the present study was taken up
      to survey the status of common water-borne diseases epidemiological trends in the
      desert city Bikaner (NW Rajasthan). In the city, 15.5 per cent population and
      44.5 per cent families were found to suffer from one or more common water-borne
      diseases including amoebiasis, diarrhoea, dysentery, jaundice and typhoid. No
      case of fluorosis was recorded. The highest incidence was that of diarrhoea (5.4
      per cent population). The worst affected and safe zones in the city were
      identified and the trends of different diseases in different zones of the city
      are discussed. The highest incidence of diseases was noted during summer (58.8
      per cent) followed by winter (34.1 per cent) and monsoon (7.0 per cent).
      Relationship of diseases with population attributes like age, education, economy
      and family size are also discussed. Attributes for contamination of drinking
      water have been tried to identify and safety measures suggested.

PMID- 16295688
TI  - Sero-surveillance of HIV, HBV and HCV infections in antenatal and STD clinic
      attendees.

PMID- 16295689
TI  - First confirmed case of HIV-I infection following accidental occupational
      exposure in a HCW.

PMID- 16295690
TI  - Clinical presentations of malaria during an out break situation.

PMID- 16295691
TI  - Significance of knowing baseline widal test titres in pediatric population in
      Delhi.

PMID- 16295692
TI  - Low prevalence of HCV infection among the primitive tribes of Andaman and Nicobar
      islands, India.

PMID- 16295693
TI  - A short communication: Salmonella phage types in and around Solapur (South
      Maharashtra) from 1986 to 1998.

PMID- 16295695
TI  - Anti-hyperglycemic effects of plum in a rat model of obesity and type 2 diabetes,
      Wistar fatty rat.
AB  - Dried plums, considered a healthy food in the West and used as medicine in India,
      contain phenolic compounds with protective actions against age-related diseases.
      Effects of oral plum ekisu (concentrated juice) on lipid and glucose tolerance
      were assessed in insulin-resistant obese Wistar fatty rats. Plum ingestion
      decreased blood glucose (P < 0.05) and plasma triglyceride concentrations (P <
      0.01) compared with controls. Plum treatment for 2 weeks reduced areas under the
      curve (AUCs) for glucose and insulin during a glucose tolerance test. In db/db
      mice, plum decreased these AUCs, and also blood glucose during an insulin
      tolerance test. Plum treatment significantly increased plasma adiponectin
      concentrations and PPARgamma mRNA expression in adipose tissue from Wistar fatty
      rats. Plum thus may increase insulin sensitivity in these rats via adiponectin
      related mechanisms.

PMID- 16295694
TI  - Green tea with a high catechin content suppresses inflammatory cytokine
      expression in the galactosamine-injured rat liver.
AB  - Galactosamine is known to induce hepatic injury in rats and the galactosamine
      induced hepatitis is believed to be similar to viral hepatitis both
      morphologically and functionally. In the present study, we examined how drinking
      green tea affects the gene expression of inflammatory cytokines which may be up
      regulated in galactosamine-induced hepatitis. As has been reported, galactosamine
      caused hepatic injury in rats as evidenced by an increase in serum transaminase
      activities and histological observations of the liver. The results of the reverse
      transcription and polymerase chain reaction indicated an increased gene
      expression of inflammatory cytokines, tumor necrosis factor-alpha and interleukin
      1beta, in the injured liver and the enzyme linked immunoassay showed an increase
      in the serum levels of these cytokines. Oral administration of green tea rich in
      catechins (Healthya green tea) restored these biomarkers in the galacotsamine
      treated rats to near the control levels. These results suggest that the drinking
      of green tea with a high catechin content may help to prevent and/or attenuate
      the development of a certain type of hepatitis.

PMID- 16295696
TI  - Long-lasting effects of yohimbine on the ejaculatory function in male dogs.
AB  - Previous studies have demonstrated that systemic administration of a low dose of
      the alpha2-adrenoceptor antagonists stimulates the ejaculatory response of male
      dogs, when this function is analyzed using the amount of ejaculated semen in
      response to genital stimulation. The present study was designed to further
      examine the features of the stimulatory effects of the alpha2-adrenoceptor
      antagonists on ejaculation, especially the duration of action. Treatment with
      yohimbine (0.1 mg/ kg, i.p.) to male dogs, at 0.5, 1, 3, or 5 h before the
      testing, produced a significant stimulatory effects on the ejaculatory response
      elicited by manual penile stimulation; the amount of ejaculated semen was
      increased and the onset of ejaculation was shortened following each treatment.
      However, such effects were not observed in the treatment with yohimbine at 8 and
      24 h before the testing, indicating that the ejaculatory stimulation induced by
      yohimbine lasted for a relative long period. By contrast, the stimulatory effects
      of RX821002 (0.1 mg/kg, i.p.), a selective alpha2-adrenoceptor antagonist, on
      ejaculation were observed only for 1 h after administration. To determine the
      contribution of the alpha2-adrenoceptor blockade for the long-lasting effect of
      yohimbine, we tested whether yohimbine can prevent the ejaculatory inhibition
      induced by clonidine, an alpha2-adrenoceptor agonist. The ejaculatory inhibition
      (a decrease in the amount of ejaculated semen and a delay onset of ejaculation)
      elicited by clonidine (0.05 mg/kg, i.p.; 1 h before testing) was completely
      blocked by pretreatment with yohimbine at 1 or 5 h before the testing, whereas
      the pretreatment with the drug at 24 h before the testing did not affect the
      clonidine-induced ejaculatory inhibition. These results indicate that yohimbine
      induced ejaculatory stimulation is continued for a relative long period (at least
      5 h after administration), and this long-lasting effects may be related to the
      alpha2-adrenoceptor blocking property of the drug.

PMID- 16295697
TI  - Evaluation of data in terms of two-dimensional random walk model: interaction
      between NADH-cytochrome b5 reductase and cytochrome b5.
AB  - Normally, bimolecular reactions are analyzed in terms of the Smoluchowski theory.
      However, when one attempts to generalize this analysis to cases where diffusion
      proceeds in two other than in three dimensions, one soon encounters severe
      conceptual difficulties. Although kinetic studies of membrane enzymes are
      generally difficult because the usual kinetic formalism refers to nonaggregated
      homogenous solutions, a major goal of our research is to define the molecular
      mechanism(s) by which alterations in membrane-bound substrate contents affect the
      enzyme activity in the same membrane. For that purpose, a simplified random-walk
      model was adopted in the present work. The enzyme reaction in the two-dimensional
      membrane could be calculated theoretically by applying the classical analysis of
      heat equation. As a result, the theoretical rate equation well accounting
      experimental findings was derived on the model of the liver microsomal NADH
      cytochrome b5 reductase reaction. Furthermore, it was found that the modification
      of the simple rigid-sphere collision theory by including a term called the steric
      factor was not necessary in this derived equation.

PMID- 16295698
TI  - Histochemical demonstration of a Na(+)-coupled transporter for short-chain fatty
      acids (slc5a8) in the intestine and kidney of the mouse.
AB  - Short-chain fatty acids in the intestinal lumen affect colonic cell proliferation
      as well as function as an energy source for intestinal epithelial cells. A novel
      transporter of monocarboxylates, Slc5a8, is expressed abundantly in the colon,
      where it may participate in the Na(+)-coupled absorption of short-chain fatty
      acids produced by bacterial fermentation of dietary fiber. The present study
      examined the cellular localization of Slc5a8 in the murine gastrointestinal tract
      and kidney by in situ hybridization and immunohistochemistry. The hybridization
      signals were recognized in the terminal ileum and whole length of the large
      intestine, and were especially intense in the distal colon and rectum. The
      immunoreactivity of Slc5a8 was restricted to the striated border (the brush
      border) of enterocytes, and was not present in goblet cells, Paneth cells, or
      lamina propria cells. In the kidney, proximal tubules of both the cortex and the
      outer stripe of the outer medulla intensely expressed Slc5a8 mRNA, while the
      distal portions, including the loop of Henle, lacked the signals. The renal
      Slc5a8 immunoreactivity was localized only in the brush border of proximal
      tubules, not along the basolateral membrane. Thyroid follicular cells were
      immunoreactive for Slc5a8, with predominant labeling on the apical membrane. No
      other organs, including the esophagus, stomach, liver, pancreas, and salivary
      glands contained any notable signals of Slc5a8. These findings on the cellular
      and subcellular localization of Slc5a8 under normal conditions are helpful for
      understanding the physiological and pathological roles of Slc5a8.

PMID- 16295699
TI  - Stimulation of production of glial cell line-derived neurotrophic factor and
      nitric oxide by lipopolysaccharide with different dose-responsiveness in cultured
      rat macrophages.
AB  - To understand the molecular basis of inflammation-induced neurotrophic
      influences, we investigated the effects of lipopolysaccharide (LPS) on production
      of glial cell line-derived neurotrophic factor (GDNF) in the injured rat spinal
      cord or in cultured rat macrophages in comparison with the effects on
      synthesis/secretion of inducible nitric oxide synthase (iNOS) and nitric oxide
      (NO). We found that GDNF mRNA expression lasted longer than that of iNOS mRNA in
      the injured spinal cord after injection of the high-dose LPS that had improved
      locomotor function, suggesting that the GDNF expression and its balance with NO
      generation were critical for injury regeneration. Therefore, we next investigated
      the effects of LPS on cultured macrophages. Levels of iNOS mRNA and secreted NO
      were enhanced by LPS at lower concentrations (10 ng/mL and above), whereas mRNA
      expression and secretion of GDNF were elevated only at higher concentrations (100
      ng/mL and above). The culture medium of macrophages treated with 10 ng/mL of LPS
      was actually neurotoxic against cultured cortical neurons, whereas that
      conditioned at 1000 ng/mL was not. These observations suggest that neurotoxicity
      partly based on NO is induced by a lower degree of inflammation, whereas
      neurotrophic effects based on GDNF are manifested at a higher degree of
      inflammatory activity.

PMID- 16295700
TI  - Enhancing theoretical fidelity: an e-mail-based walking program demonstration.
AB  - PURPOSE: To examine the extent to which theoretical fidelity, or precision in
      replicating theory-based recommendations, influenced the effectiveness of two
      walking programs based on social cognitive theory (SCT). DESIGN: Two-group
      randomized controlled trial. SETTING: College town in Virginia. SUBJECTS: Sixty
      one sedentary adult women. INTERVENTION: Two 12-week e-mail-based walking
      programs were compared. The high fidelity program was designed to more precisely
      follow SCT recommendations for operationalizing mastery procedures than the low
      fidelity program, which was designed to simulate how mastery procedures were
      operationalized in most existing SCT-based physical activity programs. Treatment
      contact and walking prescription were controlled across groups. MEASURES: The 1
      mile walk test of physical fitness and SCT measures were completed at baseline
      and posttest. Self-reported walking quantity was assessed at baseline, posttest,
      and 1-year follow-up. Walking logs were completed during the program. Process
      evaluation measures were completed at posttest. RESULTS: Fifty women completed
      the study. The high fidelity group improved more than twice as much as the low
      fidelity group on 1-mile walk test time (86 vs. 32 seconds, p < .05), goal
      setting (p < .05), and positive outcome expectations (p < .05) and reported
      greater program satisfaction (p < .01). CONCLUSION: Theoretical fidelity could
      advance the quality of physical activity interventions, which have often shown
      small effects.

PMID- 16295702
TI  - Ethnic disparities in the use of nicotine replacement therapy for smoking
      cessation in an equal access health care system.
AB  - PURPOSE: To examine ethnic variations in the use of nicotine replacement therapy
      (NRT) in an equal access health care system. DESIGN: Cross-sectional survey.
      SETTING: Eighteen Veterans Affairs medical and ambulatory care centers. SUBJECTS:
      A cohort of male current smokers (n = 1606). MEASURES: Use of NRT (nicotine patch
      or nicotine gum), ethnicity, sociodemographics, health status, smoking-related
      history, and facility prescribing policy. RESULTS: Overall, only 34% of African
      American and 26% of Hispanic smokers have ever used NRT as a cessation aid
      compared with 50% of white smokers. In the past year, African-American smokers
      were most likely to have attempted quitting. During a serious past-year quit
      attempt, however African-American and Hispanic smokers reported lower rates of
      NRT use than white smokers (20% vs. 22% vs. 34%, respectively, p = .001). In
      multivariate analyses, ethnicity was independently associated with NRT use during
      a past-year quit attempt. Compared with white smokers, African-American (adjusted
      odds ratio, .53; 95% confidence interval, .34-.83) and Hispanic (adjusted odds
      ratio, .55; 95% confidence interval, .28-1.08) smokers were less likely to use
      NRT. CONCLUSIONS: Assessment of variations in use of NRT demonstrates that
      African-American and Hispanic smokers are less likely to use NRT during quit
      attempts. Future research is needed on the relative contributions of patient,
      physician, and system features to gaps in guideline implementation to provide
      treatment for ethnic minority smokers.

PMID- 16295701
TI  - A systematic review of mammography educational interventions for low-income
      women.
AB  - OBJECTIVE: We conducted a systematic review to examine the effectiveness of
      educational interventions in increasing mammography screening among low-income
      women. DATA SOURCES: Bibliographic databases, including MEDLINE, The Cochrane
      Central Register of Controlled Trials, The Cochrane Database of Systematic
      Reviews, and the ISI Web of Science, were searched for relevant articles. STUDY
      INCLUSION AND EXCLUSION CRITERIA: Randomized, community-based trials targeting
      low-income women and published between January 1980 and March 2003 were included.
      DATA EXTRACTION: The search yielded 242 studies; 24 met all inclusion criteria.
      DATA SYNTHESIS: Three studies used mammography vans, three used low-cost vouchers
      or provided free mammograms, three used home visits, one used community education
      alone, one provided referrals, five incorporated multiple intervention
      strategies, two used phone calls, one used videos and print material, and five
      used primarily print material. RESULTS: Of nine studies that reduced barriers to
      care via mammography vans, cost vouchers, or home visits, eight showed
      statistically significant increases in mammography screening. Seven of the eight
      studies that used peer educators had significant increases in screening, as did
      four of the five studies that used multiple (intervention) components.
      CONCLUSIONS: Interventions that used peer educators, incorporated multiple
      intervention strategies, or provided easy access via vans, cost vouchers, or home
      visits were effective in increasing screenings. Mailed letter or telephone
      reminders were not effective in trials involving low-income women, which is
      contrary to findings from middle/upper-income studies.

PMID- 16295703
TI  - A controlled trial of a Quit and Win contest.
AB  - PURPOSE: To evaluate the impact of a state-of-the-art Quit and Win contest on
      tobacco quit rates at 3, 6, and 12 months after the 30-day quit period. DESIGN:
      Quasi-experimental with a volunteer sample of 494 Quit and Win contest
      registrants (treatment group) and 512 randomly selected tobacco users not exposed
      to the promotional media campaign (control group). Intervention included a 30-day
      quit period to be eligible for large cash prizes; provider advice via weekly
      mailings; online and telephone quit assistance; media campaign; and community
      support. SETTING: Community-based intervention in Kentucky. SUBJECTS: A total of
      1006 adult tobacco users. MEASURES: Quit rates were measured using 7-day point
      prevalence for tobacco use. Urine cotinine measurements confirmed self-reported
      quitting. RESULTS: Treatment group participants were significantly more likely
      than controls to experience quitting during the 1-year follow-up, as determined
      by both self-report and urine confirmation. After adjusting for baseline
      differences in demographics, tobacco use, and stage of change, those in the
      treatment group had 2.6 times the odds of reporting quitting in the
      postintervention period and 5.3 times the odds of experiencing quitting confirmed
      by urine cotinine, relative to controls. Women, minorities, and low-income
      tobacco users had equal odds of quitting as men, whites, and those with higher
      incomes. CONCLUSIONS: That the contest was minimally intensive and yielded a
      relatively high, quit rate demonstrates the potential effectiveness of the
      intervention.

PMID- 16295705
TI  - Change in self-efficacy following a single strength training session predicts
      sedentary older adults' subsequent motivation to join a strength training
      program.
AB  - PURPOSE: To determine whether performance accomplishment and perceived exertion
      predict change in self-efficacy following a single strength training session and
      whether change in self-efficacy predicts subsequent motivation to join a strength
      training program. METHODS: Fifty-nine sedentary older adults participated in a
      single strength training session at a seniors' exercise center, completed
      measures of perceived exertion and self-efficacy, and received a voucher for a
      free fitness consultation. RESULTS: Regression analyses indicated that perceived
      exertion predicted change in self-efficacy. In turn, greater change in self
      efficacy was associated with a greater likelihood of using the voucher for a
      fitness consultation. DISCUSSION: Sedentary older adults can be motivated toward
      joining a strength training program after an initial strength training session
      that required low exertion. Practitioners could increase strength training
      initiation by providing such experiences.

PMID- 16295704
TI  - Is stress management training a useful addition to physician advice and nicotine
      replacement therapy during smoking cessation in women? Results of a randomized
      trial.
AB  - PURPOSE: To determine whether a stress management (SM) program could improve
      cessation rates when added to usual care (UC) among women attempting to quit
      smoking. DESIGN: Randomized controlled trial conducted during a 12-month period.
      SETTING: Smoking cessation clinics located within two tertiary care centers in
      Ottawa, Ontario. SUBJECTS: A total of 332 women smokers 19 years or older who
      smoked 10 or more cigarettes per day were recruited via advertisements.
      INTERVENTION. Either UC (physician advice and nicotine replacement therapy) or UC
      plus an eight-session group SM training program (coping skills development
      relevant to smoking-specific and generic stressors). MEASURES: Point prevalence
      abstinence 2 and 12 months after study intake. A secondary outcome of interest
      was change in perceived stress during the intervention period. RESULTS: On an
      intent-to-treat basis, the addition of SM to UC had no incremental effect on 2-
      or 12-month abstinence rates. Abstinence rates at 2 months were 26.2% vs. 31.7%
      in the UC and SM groups, respectively (p = .59). At 12 months, the rates were
      18.5% vs. 20.7% (p = .86). When quit rates were compared including only
      participants who demonstrated adequate adherence to the intervention protocol,
      there was a significant difference between the UC and SM groups at 2 months
      (34.9% vs. 48.7%; adjusted odds ratio, 1.88; 95% confidence interval, 1.04-3.42;
      p = .04) but not at 12 months (23.0% vs. 28.2%; adjusted odds ratio, 1.24; 95%
      confidence interval, .64-2.41; p = .53). There was a significant reduction in
      perceived stress from preintervention to postintervention; however, this decrease
      was not moderated by group assignment. CONCLUSION: The addition of SM in our
      setting neither increased abstinence rates nor reduced perceived stress over and
      above UC in women motivated to quit smoking. Poor attendance at the SM
      intervention undermined its effectiveness.

PMID- 16295707
TI  - Overcoming cultural roots of obesity and inactivity: employers respond.

PMID- 16295706
TI  - How do perceptions of local neighborhood relate to adolescents' walking and
      cycling?
AB  - PURPOSE: To examine how perceptions of the local neighborhood relate to
      adolescents' walking and cycling. DESIGN: Exploratory cross-sectional study.
      SETTING: Birth cohort from the Nepean Hospital, Sydney, Australia. SUBJECTS:
      Three hundred forty-seven adolescents (79.1% response rate; 49.6% boys; mean age
      = 13.0 +/- 0.2 years) and their parents. MEASURES: Self-report and parental
      report questionnaires. RESULTS: Multiple linear regressions, adjusted for level
      of maternal education, revealed that boys who reported having many peers to hang
      out with locally, cycled for recreation (beta = 0.242, p = .006) or for transport
      (beta = 0.141, p = .046) more often, and walked for transport for longer (beta =
      0.129, p = .024) on weekdays. For girls this variable was related to cycling for
      recreation on weekends (beta = 0.164, p = .006) and walking to school (beta =
      0.118, p = .002). Adolescents who waved/talked to neighbors walked for transport
      more often (boys, beta = 0.149, p = .037; girls, beta = 0.119, p = .012). Girls
      who perceived local roads to be safe spent more time walking for transport on
      weekdays (beta = 0.183, p = .007) and for exercise on weekends (beta = 0.184, p =
      .034). Parents' perception of heavy traffic was negatively associated with boys'
      walking for transport (beta = -0.138, p = .037) and many aspects of girls'
      walking and cycling. CONCLUSION: Social interaction and road safety may be
      important predictors of adolescents' walking and cycling in their neighborhood.
      Limitations are the use of self-report and cross-sectional data. Longitudinal
      studies may clarify these relations.

PMID- 16295708
TI  - [Cavity micro-morphology following caries removal].
AB  - The objective of this research was to observe the effect of different caries
      removal techniques on human dentin topography. Thirty-six dentin samples of
      bisected carious human molars were treated with six different caries removal
      techniques, replicated and then examined by using a scanning electron microscope.
      The surfaces were observed before and after the smear layer removal at a
      magnification of 200- and 1000-fold. At a magnification of 200 the sono-abraded
      samples showed a significantly more undulated dentin topography than samples
      treated with other techniques. Using Carisolv hand instruments for caries removal
      resulted both at a magnification of 200 and 1000 in a significantly rougher,
      flakier and more fissured dentin surface texture compared to other techniques.
      Microcracks were observed in samples from all excavation methods but most
      frequently when treated with Carisolv hand instruments. The excavation process
      results in a dentin topography marked by smooth, flaky and fissured surface
      textures as well as by microcracks. The relative incidence in which these
      textures occur may indicate whether the removed dentin was rather cut or
      fractured.

PMID- 16295709
TI  - [Periotest-analysis in penradicular surgery: preliminary results of a clinical
      prospective study].
AB  - The two objectives of the present study were: to assess the healing after
      periradicular surgery using the Periotest device, and to compare the recorded
      Periotest values with the healing category determined after a one-year follow-up
      using radiographic and clinical criteria. In 43 patients with periradicular
      surgery, Periotest values could be recorded pre- and postoperatively, as well as
      after six and twelve months. Cases with a successful healing, as determined at
      the one-year follow-up, demonstrated a continuous decrease of the Periotest
      values over time, whereas one-year failures showed increasing Periotest values
      over the study period. In control teeth, the Periotest values remained unchanged
      for the whole study period. It appears that the Periotest measurements correlate
      with the postoperative healing mode following periradicular surgery, and
      therefore, allow an additional assessment of the healing outcome.

PMID- 16295710
TI  - [Erosion. Clinical aspects--diagnosis--risk factors--prevention--therapy].
AB  - Dental erosions have a multifactorial genesis. Acids of intrinsic and extrinsic
      origin are thought to be the main aetiologic factors, but also abrasive
      components can be involved in tooth destruction. This overview gives information
      about the clinical appearence and the risk factors for the developement of
      erosive lesions. In addition, preventive and therapeutic measures are discussed.
      The knowledge about the patient's history, the accurate clinical examination and
      the correct diagnosis are prerequisites for an adequate preventive and
      therapeutic concept. It is important to get data about diet habits and host
      factors like salivary flow rate, buffering capacity and pH as well as intrinsic
      factors like the occurence of gastroesophageal reflux or vomiting. A novel scheme
      showing the dependences of the different risk factors is given. To determine the
      patient's individual risk for erosion, the dentist must be able to assess the
      erosive potential of these parameters. Data about the distribution and clinical
      appearance of erosive defects, photographs and study casts are important to plan
      the prevention and therapy and to judge the success of such measures.

PMID- 16295711
TI  - Utility of specific IgG4 response in saliva and serum samples for the diagnosis
      and follow up of human neurocysticercosis.
AB  - This study was aimed to analyze the Ig subtypes and IgG1 and IgG4 subclass
      responses to crude soluble extract (CSE) antigen and Ag B of Cysticercus
      cellulosae in pre and post treatment (PT) saliva and serum samples for the
      diagnosis and follow-up of neurocysticercosis (NCC) patients. Saliva and serum
      samples collected from 55 patients (15 highly suggestive of NCC clinically and
      radiologically, 10 hydatidosis, 10 other helminthic infections, 10 tubercular
      meningitis, 10 neurological disorders other than NCC), 15 normal healthy subjects
      and 10 NCC patients at 1, 3 and 6 months following albendazole therapy were
      analyzed for specific IgG, IgG1, IgG4, IgM and IgA antibody responses by ELISA.
      With the use of CSE Ag, the rank orders in saliva for sensitivity was IgG (71.4%)
      > IgG1 (68.2%) > IgG4 (65.2%) > IgM (57.7%) > IgA (55.5%) and specificity IgG1 =
      IgA (93.2%) > IgG = IgG4 = IgM (91.6%) while in serum, sensitivity was IgG
      (78.9%) > IgG1 (71.4%) > IgG4 (68.2%) > IgA (65.2%) > IgM (62.5%) and specificity
      IgG1 = IgG4 (90.2%) > IgA (85.9%) > IgG (83.3%) > IgM (82.1%). With the use of Ag
      B in saliva, the sensitivity was IgG (65.2%) > IgG1 = IgG4 (62.5%) > IgM = IgA
      (55.5%) and specificity with the use of saliva was IgG1 = IgG4 = IgM (94.8%) >
      IgG (93.2%) > IgA (91.6%) while with serum the sensitivity was IgG = IgG1 (68.2%)
      > IgG4 (65.2%) > IgA (62.5%) > IgM (57.7%) and specificity was IgG1 (93.2%) >
      IgG4 = IgM (91.6%) > IgA (90.2%) > IgG (87.3%). Comparative analysis of antibody
      responses in patients with single Vs multiple CT scan lesions indicated higher
      sensitivity in multiple lesion patients. Antibody responses in PT samples
      indicated that the undetectable IgG4, IgM and IgA responses in saliva samples
      correlated well with the CT scan reports while in serum samples, responses
      persisted longer. In conclusion, this study indicated that due to the lower
      sensitivity of IgM and IgA responses in pretreatment samples, detection of IgG4
      subclass in saliva to either CSE Ag or AgB may serve better marker in the NCC
      follow-up.

PMID- 16295712
TI  - Neuroembryopathic effect of clobazam in rat: a histological study.
AB  - Clobazam is a derivative of the benzodiazepines used as an anti-epileptics drug.
      The pregnant rat had received, orally, 125 mg/kg of clobazam daily from 1st-7th
      day of gestation and fetuses were collected on 20th day of pregnancy. Brain of
      the clobazam treated fetuses showed no significant change in weight and size in
      comparision to that of the controls. Other gross abnormalities were also not
      found in the brains of treated group. Histological examination revealed the
      alteration in cytoarchitecture of the cerebral and the cerebellar cortex. Strips
      of focal coagulate necrosis extended through most of the layers of the cerebral
      cortex. There were paucity of neurons and neurological elements in the cortex and
      the central grey area of spinal cord. Many of these neurons showed pyknotic
      nuclei. The intercellular spaces increased either because of decrease in cell
      number or due to shrinkage and clumping of degenerated neurons. Subcortical
      (white matter) zone showed the paucity and derangement of the oligodendrocytes
      and the astrocytes, which revealed vigorous proliferation in the treated group.
      These findings showed that the benzodiazepines and their derivatives have
      teratogenic effect in the developing mammalian central nervous system.

PMID- 16295713
TI  - Variations in branching pattern, shape, size and relative distances of arteries
      arising from arch of aorta.
AB  - Hundred aortic arches were studied in adult cadavers (aged 40-70 years) for
      variations in the origin of branches at arch of aorta in situ and for observing
      the lumenal diameters and relative distances between the adjacent branches.
      Usually described three branches arising at arch of aorta were observed in 77.0%
      specimens. Two branches arising from arch of aorta, having different branching
      pattern were observed in 12.0%:--(i) BC trunk; left brachiocephalic which divided
      into right common carotid and right subclavian (ii) common origin of BC and LCC;
      LSC. (iii) common origin of BC and LCC; common origin of LSC and left vertebral.
      While, four branches were observed in 11.0% showing separate openings:--(i) BC;
      LCC; LV; LSC (ii) BC; thyroid ima; LCC; LSC (iii) BC, mediastinal; LCC; LSC. At
      the lumenal surface of the arch of aorta the lumenal openings showed a similar
      pattern corresponding to the arterial branches on the external surface. These
      openings were oval in shape in 90.0% with the mean maximum anteroposterior
      diameters being greater than the mean maximum side-to-side diameters (p < 0.001),
      while they were elliptical in 10.0%. The BC artery showed largest size followed
      by LSC and then LCC in most of the branching patterns (p< 0.001). The mean
      transverse distances between adjacent lumenal openings of these branches were
      significantly greater than the mean vertical distances (p < 0.001). Approximation
      of LCC to BC trunk was seen in 10.0% specimens. These observations may be
      important while invading the arch of aorta and its branches by instruments, as
      all areas are now susceptible to surgical attack.

PMID- 16295715
TI  - Study of anomalous drainage pattern of right testicular vein.
AB  - The present paper describes the study of the drainage pattern of right testicular
      vein (RTV). Forty two cadavers were dissected on both sides and the anatomy of
      the drainage pattern of RTV was studied. The drainage pattern of RTV in 41
      cadavers were found to be normal i.e into inferior vene cava (IVC). An anomalous
      drainage of RTV into right renal vein (RRV) was identified in a 52 year old male
      cadaver. The anatomical knowledge of normal and abnormal drainage pattern of
      testicular veins is important for vascular surgeons. Knowledge of anomalies of
      renal vessels is of great surgical interest, as it may check accidental
      manipulation during renal surgeries which could otherwise lead to tissue necrosis
      or systemic hypertension.

PMID- 16295714
TI  - Microbiology of dacryocystitis among adults population in southern Australia.
AB  - Retrospective study on microbiology of dacryocystitis cases in adults was carried
      out at the Royal Victorian Eye and Ear Hospital (RVEEH). Sixty-four consecutive
      cases seen between March 2000 and June 2003 were included. Seventy-nine organisms
      were isolated from the sixty-six samples (1.2/specimen). Aerobic or facultative
      bacteria were recovered in 76 (96.2), fungi from two specimens (2.5%). And
      anaerobic bacteria from only one specimen (1.3%). Staphylococcus aureus (27), was
      most common followed by Pseudomonas aeruginosa (6), Proteus mirabilis (4),
      Hemophilus parainfluenza (4) and H. influenza (4). Fifty-four samples showed
      single organism while 12 samples showed multiple organisms. Overall, Gram
      positive organisms were predominating (54.4%) over Gram negative (41.8%)
      organisms. The current bacteriology of lacrimal duct obstruction in the
      population served by the RVEEH should be taken into account while selecting first
      line antimicrobial treatment for dacryocystitis and in prophylaxis in lacrimal
      drainage surgery.

PMID- 16295716
TI  - Salmonella bacteraemia in Pokhara: emergence of antibiotic resistance.
AB  - We undertook a retrospective hospital based study of 2,354 blood culture
      specimens from June 2000 to May 2003 in order to determine the isolation rates of
      Salmonella species and their antibiotic susceptibility patterns in western Nepal.
      Blood samples were cultured and identification of Salmonella species. and their
      antibiotic susceptibility testing were done as per standard protocol. Of the
      total 114 (4.8 %) yielded Salmonella species. Of them 76 (66.7%) Salmonella typhi
      and 38 (33.3%) S. paratyphi A. S. typhi was found to be the predominant species
      each year. Higher proportion of Salmonella bacteraemia was seen in adults, with a
      clearcut male to female preponderance (1.8:1). Monsoons enhanced the risk of
      acquiring enteric fever. There is also a rise in the number of multi-drug
      resistant strains in and around Pokhara Valley, with 40.7% S. typhi and 5.2% S.
      paratyphi A showing resistance to two or more antibiotics. These isolates were
      primarily resistant to the first line drugs namely Ampicillin, Chloramphenicol
      and Cotrimoxazole but susceptible to third generation Cephalosporins. Appearance
      of multi drug resistance poses considerable threat of increased morbidity and
      mortality in this region. This emphasizes the need for prudent use of
      antimicrobials.

PMID- 16295717
TI  - Improving access to drugs by poor households through a cost sharing drug scheme:
      a wealth ranking approach.
AB  - In Nepal lack of drugs in government health institutions has markedly reduced
      access to essential drugs by poor patients. Despite the implementation of a drug
      scheme with adequate availability of drugs and with provision of fee exemption
      for the poor, the poorest people still had no access to drugs. We carried out a
      wealth ranking process to identify poorest of the poor households in a village.
      Each of the poorest household was provided with a free treatment card and
      information about the availability of free service at the local health post.
      Baseline and post intervention data on service utilisation and prescribing
      practices were collected using carbon copies of prescriptions. Data were also
      collected about the attitude of patients, using qualitative interviews. About
      1.8% of the total annual patient visits to the Health Post were from cardholder
      households. The annual health post utilization rate for the poor patients was
      about 1.2, whereas among other patients it was 0.7. On average, about 2.4 drugs
      were prescribed to any of the cardholder patients, and 50.8% of prescriptions
      included at least one antibiotic drug. No injection was prescribed. Within 18
      months, the total fee exemption provided to a poorest household was equivalent to
      about US dollars 1.6. Since the method is valued by local people, and is also
      feasible to implement through the communities' efforts, it is recommended to
      initiate it in other drug scheme areas as well.

PMID- 16295718
TI  - Sleep apnoea syndrome in Nepal.
AB  - Sleep apnoea syndrome is a well recognized entity. Sleep studies of diagnosed
      patients with sleep apnoea were analyzed to understand the clinical profiles of
      Nepalese patients with this disorder. Eighty nine patients were diagnosed to have
      sleep apnoea syndrome during the period of 15 months starting from November 2003.
      All these patients were subjected to a detailed clinical evaluation including
      symptoms, presence or absence of other risk factors and co-morbidities, general
      physical and systemic examination and relevant investigations before performing
      polysomnography. Clinical profiles of patients who were confirmed to have sleep
      apnoea syndrome with apnoea hypopnoea index (AHI) more than five were included in
      the study. Forty one patients (46.1%) were found to have mild disease (AHI 6-20),
      22 patients (24.7%) had moderate disease (AHI 21-40) and 26 patients (29.2%) were
      found to have severe disease. The common symptoms were snoring, excessive daytime
      sleepiness, frequent awakenings, nocturia, and choking spells during sleep.
      Obesity was found to be the most important risk factor associated with sleep
      apnoea. Males having collar size more than 16 inches and females with collar size
      more than 14.5 inches were found to have an increased risk to develop this
      problem. Hypertension (66.3%), chronic obstructive pulmonary disease (43.2%) and
      cardiac diseases (19.1%) were the common co-morbidities associated with this
      disorder. Sleep apnoea syndrome is not an uncommon problem in Nepalese
      population. It could be the cause of various cardiovascular problems and may
      complicate patients with chronic obstructive pulmonary disease.

PMID- 16295719
TI  - Effect of application of gyrosonic waves through brain on arthritic pain and
      migrainous headache.
AB  - Gyrosonic waves created by placing the recorded sound waves on an oscillating
      frequency device has been utilized to alleviate long-standing pain in patients
      suffering from arthritis of various types and in migrainous headache. It was
      interesting to observe that arthritic pain had disappeared totally or there was
      about 80 to 90.0% reduction with planned installation of gyrosonic waves through
      headphone. Individuals with a long history of migrainous headache also had
      complete relief after a few installations; it appears that gyrosonic waves would
      be of immense help for the treatment of pain due to aforesaid problems.

PMID- 16295720
TI  - Retrospective study of chest wall tumors at a cancer hospital in Nepal.
AB  - Primary and metastatic tumors of both soft tissues and bony skeleton, and primary
      tumors of adjacent organs invading the chest wall constitute chest wall tumors. A
      retrospective review of all the patients with chest wall tumors was done at BP
      Koirala Memorial Cancer Hospital (BPKMCH). Primary tumors of breast were
      excluded. Surgical treatment consisted of wide local excision (WLE). Chest wall
      reconstruction, if needed, was achieved by a muscular flap +/- prolene mesh +/-
      omental transposition. Thirty one patients were treated in the period from
      October 1999 to October 2003. Age of the patients varied from 3 years to 72 years
      (mean age--38 years). Presenting complaint was mass in 96.8% and pain in 48.4%
      cases. The mass was 5 cm or less in 34.4%, from 5 to 10 cm in 32.3%, and more
      than 10 cm in 32.3% cases. The lesions were located in sternal region, anterior,
      lateral, posterior, and vertebral chest wall in 6.5%, 32.3%, 41.9%, 16.1% and
      3.2% respectively. WLE was done in 29 cases. Chest wall reconstruction using both
      muscular flaps and prolene mesh (15x15 cm) was done in 8 cases. In three of them,
      where concomitant wedge resection of the lung was done, omental transposition was
      added. In rest of the cases, primary closure, muscular/myocutaneous flap or skin
      grafting was done. Minor complications were observed in 31.0% cases, which were
      managed conservatively. Two patients received adjuvant radiotherapy and four
      patients--adjuvant chemotherapy. There were no postoperative deaths. The rate of
      malignancy was 48.4%.

PMID- 16295721
TI  - Factors associated with intestinal parasitic infection among school children in a
      rural area of Kathmandu Valley, Nepal.
AB  - We studied predisposing factors of enteric parasitic infections in school
      children [n=340 (Boys: 177 and Girls: 163)] in a rural area in Kathmandu Valley,
      Nepal. Fecal samples were examined by formal-ether concentration technique. A
      total of 71.2% children had parasite. Altogether nine types of parasites were
      recovered; Trichuris trichiura was the commonest one followed by hookworm and
      others. A structured questionnaire regarding various predisposing factors was
      used. No significant differences in the infection rate between the sexes, age
      groups (< or = 10 years, 11-14 years and > or = 15 years) and family sizes (< or
      = 5 and > or = 6) were observed (P>0.05). The positive rates were significantly
      low in children with the history of taking antihelminthic drugs in the past six
      months (P<0.05). A marginally higher positive rate was found among Dalits
      children compared to Tibeto-Burmans and Indo-Aryans (P>0.05) and children from
      farming family (P>0.05). No difference in the infection rate was found in
      children having different types of toilet facility: open-field defecation, pit
      latrine and modern toilet at their houses (P>0.05). Slightly higher positive rate
      was associated with drinking water from Kuwa (shallow well) compared to natural
      spout, piped water and Khola (river) (P>0.05). Children were infected despite of
      their awareness regarding the safe water and geophagy.

PMID- 16295722
TI  - Intervention studies on rational use of drugs in public and private sector in
      Nepal.
AB  - In developing countries, inappropriate, inefficient and ineffective use of
      pharmaceuticals have resulted into the poor health and medical cares for the
      community people. For improving the situation, various interventions have been
      tested and proved effective in different settings. In Nepal also, various
      strategies have been tested and found effective to improve the prescribing and
      dispensing practices. This paper has examined the process and results of
      different studies. The educational intervention, the training has not been
      effective in improving the prescribing practices but has limited effect on
      dispensing practices in the public sector. However, it becomes effective in
      improving prescribing practices if combined with a managerial intervention e.g.
      peer-group discussion. In private sector, training alone is effective in changing
      the drug recommendation practices of retailers. But none of interventions have
      been found to be effective in improving dispensing practices. After examining the
      effectiveness of different interventions, training combined with peer-group
      discussion is recommended for piloting in all Primary Health Care (PHC) outlets
      of a district to improve the prescribing practices. For improving the dispensing
      practices in both public and private sector, additional studies have to be
      carried out using different strategies.

PMID- 16295723
TI  - Knowledge, attitude and practice (KAP) study on diabetes mellitus among Nepalese
      diabetic patients.
AB  - Present study was carried out to understand the knowledge, attitude and practices
      (KAP) regarding diabetes mellitus (DM) among the diabetic patients attending a
      diabetic education programme. Results showed that the majority of patients had
      correct knowledge regarding diabetic diet, three-fourths of them were subjected
      themselves to blood sugar checking at good intervals and almost all were under
      regular contact with physicians. This study might help in implementation of
      diabetic education programme giving more emphasis among older and younger groups
      of patients and encouraged the patients to have more contact with concerning
      physicians, so that complications that occurring at early stage of disease could
      be prevented.

PMID- 16295724
TI  - Profile of blindness in Nepal: a hospital based study.
AB  - A hospital based prospective study was conducted at B P Koirala Lions Center for
      Ophthalmic Studies to determine the causes of blindness. A total of 701 patients
      were enrolled for this study during a one and a half year time period. Four main
      diseases in the order of prevalence--cataract, corneal diseases, trauma and
      posterior segment diseases--were identified as the major causes of blindness. The
      prevalence of blindness increased with age and showed a male preponderance.
      Cataract and corneal diseases were the leading causes of bilateral blindness and
      unilateral blindness respectively.

PMID- 16295725
TI  - Perception of final-year medical students about skills attainment in a new
      medical school of Nepal.
AB  - The competence of clinical and procedural skills possessed by medical students on
      graduation have received considerable importance in recent years. This
      questionnaire-based study was conducted at B.P. Koirala Institute of Health
      Sciences, Dharan, Nepal with an aim to assess the perception about clinical and
      procedural skills attainment by final-year medical students in a new medical
      school of Nepal. Fifty-nine final year MBBS students were interviewed using a set
      of questionnaire related to the experience gained by the students in relations
      eight clinical and twenty procedural skills. The perception about the level of
      attainment was good for most of the clinical skills and for few procedural
      skills, for example, using an auroscope and ophthalmoscope. The level of
      attainment was very poor in inserting the flatus tube, aspirating pleural and
      ascitic fluids, performing lumbar puncture, administering enema and giving
      subcutaneous injection. The perceived confidence in giving intravenous injection,
      inserting venflons, catheterizing urinary bladder, performing ambu bag and mask
      ventilation, proctoscopy and suturing of superficial wound was greater than the
      level of practical experience. The practical experience was more in doing
      venesection but the perceived confidence was poor in it. The final year medical
      students had mastered most of the clinical skills but not all procedural skills
      equally. Those skills in which they are not competent must be acquired during
      internship. Training in these skills needs to be reinforced by establishing a
      skill laboratory.

PMID- 16295726
TI  - Influence of moonlight on the birth of male and female babies.
AB  - Effects of full moon and no moon on the birth of male and female offsprings were
      studied in Indian Couples of the age group 20 to 40 years. It was observed that
      42 wives who were conceived within 24 hours of ovulation at full moon gave birth
      of 40 male and 2 female babies. On the other hand 40 women conceived on the day
      of ovulation 3 days prior to full moon gave birth of 13 male and 27 female
      babies. But only 5 women conceived on no moon, all of them gave birth of female
      babies. It was also observed that vaginal pH of the ovulated women during full
      moon was alkaline (pH 8.7 +/- 0.4) while pH was weak acidic in women ovulated 3
      days prior to full moon and no moon (pH 6.4 +/- 0.5; 6.2 +/- 0.5). The basal body
      temperature (BBT) was increased 0.7 degrees F to 1.3 degrees F during the
      ovulation period when compared with women during the absence of ovulation. But
      there is an increase in temperature 0.5 degrees F more in women ovulated in full
      moon than no moon. Together, these results indicate that alkaline vaginal fluid
      medium and more rise of BBT during full moon favour conception of male
      [corrected] babies. This method gives the couple more chance of having male child
      if conception occurs in the day of ovulation in full moon and having female child
      if conception occurs in no moon.

PMID- 16295727
TI  - Cancer: determinants and progression.
AB  - Cancer is the combination of uncontrolled cellular proliferation and immortality.
      It is a multi-step disease with a multi-factorial etiology. The determinants of
      cancer are many and varied including genetic predisposition, environmental
      influences, infectious agents, nutritional factors, hormonal and reproductive
      factors, radiation etc. However, the extent of the genetic involvement and their
      interaction with environment in tumorigenesis is still elusive. The six essential
      alterations in cell are proposed which determines the transition from normal cell
      to malignant. It includes--self-sufficiency in growth signals, insensitivity to
      growth-inhibitory (antigrowth) signals, evasion of programmed cell death
      (apoptosis), limitless replicative potential, sustained angiogenesis, and tissue
      invasion and metastasis. Nevertheless, the last two decades have seen rapid
      improvements in understanding the complex molecular mechanisms underlying
      tumorigenesis, yet the quest for unraveling the mystery is not over. Further
      study in this area is indispensable that could hold the promise of increasing our
      understanding of cancer etiology and possible preventive strategy.

PMID- 16295728
TI  - Awareness of sudden infant death syndrome needed in Nepal.
AB  - The author during his visit to different private and public hospitals of
      different parts Nepal found that doctors are not so much aware of Sudden Infant
      Death Syndrome (SIDS). In most of the hospitals, if an infant comes to the
      emergency department or baby dies in the post natal care/neonatal room then they
      are asked to take the baby without doing proper investigations. The practice
      should be in a broader concept in the sense that if such type of case comes then
      a full clinical history, examination of death scene and a complete autopsy should
      be done. This article reflects the importance of SIDS and makes aware the doctors
      and other paramedics about it.

PMID- 16295729
TI  - Nocardial brain abscesses in a HIV positive patient misinterpreted as tubercular
      brain abscesses.
AB  - We present a case of nocardial (Nocarda transvalensis) brain abscesses in a HIV
      infected person with CD4 count of 53 cells/ml, who received antitubercular
      therapy for one year. A magnetic resonance imaging study showed multiple ring
      enhancing lesions in right parieto-occipital parenchymal region along with
      perilesional edema and mass effect. Right posterior temporal burr hole aspiration
      of the abscesses and postoperative cotrimoxazole and ampicillin-sulbactum therapy
      cured the patient. It is a case of HIV infection with rare and sole manifestation
      of multiple cerebral abscesses due to N. transvalensis.

PMID- 16295730
TI  - Dysphagia as a presenting symptom in a case of dermatomyositis and occult gastric
      malignancy.
AB  - A case of dermatomyositis in a 64 yrs old male with occult gastric malignancy is
      presented along with a brief review of literature.

PMID- 16295731
TI  - Budd-Chiari syndrome--a case report.
AB  - A 21year old male presented with abdominal pain for 2 months and abdominal
      distension and swelling of lower limbs for 1 month. Ultrasonography of abdomen
      showing coarse echotexture of liver and intraluminal filling defect of inferior
      vena cava (IVC) and CT scan confirming the USG finding and showing enlarged
      caudate lobe of liver and thrombus in proximal IVC suggested the possibility of
      Budd-Chiari syndrome. Confirmation of diagnosis was done by inferior
      venacavography. The patient had nephrotic syndrome as the risk factor for
      thrombosis. The patient was portally decompressed by portocaval shunt with
      significant symptomatic relief.

PMID- 16295733
TI  - An autopsy study of atherosclerosis in aorta, common carotid arteries and circle
      of Willis.
AB  - The incidence, extent and degree of atherosclerosis was studied in descending
      aorta, common carotid arteries and circle of Willis obtained from 50 cadavers
      above the age of 30 years. Specimens were stained grossly with Sudan IV and the
      total atherosclerotic area was measured and atherosclerotic index was calculated.
      The co-efficient of correlation between extent of atherosclerosis with age and
      nutritional status was calculated. The incidence of atherosclerosis was 100.0% in
      the aorta and common carotid arteries in all the specimens. In case of circle of
      Willis, it was 76.5% in the fourth decade and 87.5% in the fifth decade, rising
      to 100.0% thereafter. The atherosclerotic index increased with age at all the
      three locations. However, at any given age, the atherosclerotic index in circle
      of Willis was much less as compared to the aorta or common carotid arteries. The
      most prominent lesion in all the three groups of vessels in the fourth and fifth
      decades was the presence of a fatty streak. There was a sudden spurt in the
      extent of fibrous plaques in the aorta, carotid arteries and circle of Willis in
      the sixth decade. Complicated lesions also appeared in this decade, and became
      more marked after sixty years of age. The correlation between the extent and
      degree of atherosclerosis with age was found to be highly significant
      statistically (p < 0.001). A significant correlation (p < 0.001) was also found
      between the nutritional status and extent and degree of atherosclerosis. No
      conclusion could be derived regarding differences in the extent and degree of the
      disease in the two sexes.

PMID- 16295732
TI  - Choroidal effusion following laser peripheral iridotomy for the treatment of
      angle closure glaucoma in a patient with nanophthalmos.
AB  - We report a case of Nanophthalmos with choroidal effusion and retinal detachment
      following a peripheral laser iridotomy for the treatment of angle closure
      glaucoma. Angle closure glaucoma was diagnosed in the right eye of the patient
      after finding an elevated intraocular pressure and narrow angles on gonioscopy.
      The glaucoma was treated by lowering the intraocular pressure medically followed
      by laser peripheral iridotomy. The first day after a laser peripheral iridotomy,
      choroidal effusion was noticed that was followed by an exudative retinal
      detachment within a week. The medical and laser therapies for the lowering of
      intraocular pressure for the treatment of angle closure glaucoma in patients with
      nanophthalmos can be associated with choroidal effusion, retinal detachment and
      loss of vision.

PMID- 16295734
TI  - Evaluation of rapid diagnostic methods for pediatric viral diarrhea using samples
      collected in Nepal and Japan.
AB  - We evaluated real time PCR, ELISA and immunochromatography (ICG) test systems for
      detection of diarrheagenic viruses (Rotavirus, Adenovirus and Norovirus) in
      pediatric diarrheal fecal samples collected in Kathmandu, Nepal (n = 23) and in
      Kobe, Japan (n = 25) in summer of 2004. Of the 23 samples collected in Nepal, one
      (4.3%) was positive for Rotavirus and two (8.7%) for Adenovirus whereas six out
      of 25 samples (24.0%) collected in Japan were positive for Norovirus. Of the
      Japanese samples, 11 (44.0%) showed diarrheagenic bacteria (Campylobacter jejuni,
      Salmolella enteritidis) while six (26.1%) samples from Nepal showed parasites
      like Ascaris lumbricoides, Giardia intestinalis, Trichuris trchiura and
      Vampirolepis nana. Viral pathogens were not common during summer season in both
      Nepal and Japan. Real time RT-PCR was found to be relatively more sensitive
      compared with ELISA for Norovirus. However, immunological methods are simple and
      less time consuming (three hours for ELISA, 15 minutes for ICG) and appeared to
      be useful for rapid diagnosis of viral gastroenteritis especially in developing
      countries.

PMID- 16295735
TI  - Sero-molecular evaluation of human cytomegalovirus disease in renal transplant
      rejection.
AB  - Cytomegalovirus (CMV) is the most common viral pathogen in renal transplant
      recipients resulting in graft rejection. The prevalence of CMV disease and renal
      graft rejection is not well studied in India. Sequential specimens from 32 renal
      allograft recipients were examined by using CMV IgM specific mu capture ELISA and
      DNA by PCR. Twelve of the 32 patients were CMV IgM positive and out of 12
      patients, 9 had rejection and 4 experienced CMV disease. CMV IgM specific mu
      capture ELISA helped in diagnosis of CMV disease, though it is less sensitive in
      detection of rejection. PCR itself was proved not sensitive enough in detecting
      either CMV disease or rejection. At present, optimal laboratory detection of CMV
      infection in these patients can be achieved only by multiple and more sensitive
      parameters.

PMID- 16295736
TI  - Anatomical variation in origin and course of the thoracoacromial trunk and its
      branches.
AB  - The variations in origin and course of the thoracoacromial trunk (TAT) and its
      branches were studied in 178 cadavers during the routine dissection from the year
      1982 to 2002. The TAT originated from the first part of the axillary artery (AA)
      in 13.4% cases of the right and 10.6% of the left axilla. The variations in
      origin of the branches of TAT were divided into three groups. First variation
      group showed deltoacromial (DA) and clavipectoral (CP) subtrunks of the TAT
      originating directly from the AA in majority of cases. Second group revealed
      clavicular branch of the TAT originating from the AA, whereas in the third group
      all classical branches originated directly from the AA and there was no existence
      of the TAT. The superior thoracic artery (STA) originated from the TAT in 16.8%
      (Confidence Interval, CI: 11.12-21.89) cases of the right and 6.1% (CI: 2.59
      9.53) of the left axilla and the lateral thoracic artery in 39.8% (CI: 32.01
      46.10) cases of the right and 29.3% (CI: 15.01-26.80) of the left axilla. The
      incidence of variations in origin of the TAT and its branches was found higher on
      right side. The knowledge of these variations is of anatomical and surgical
      interest. This information is useful for the surgeons dealing with the axillary
      region especially in case of reconstructive surgery.

PMID- 16295738
TI  - Gender difference in socio-epidemiological factors for leprosy in the most hyper
      endemic district of Nepal.
AB  - Leprosy which has caused stigma and social ostracism for millennium is nearing
      elimination worldwide as a public health problem, but the leprosy burden in Nepal
      is still 4.4 times greater than WHO's target level of less than one case per
      10,000 population. Although leprosy affects both the sexes, in most parts of the
      world males are affected more than females at a ratio of 2:1. The general
      objective of the study was to investigate the gender difference in socio
      epidemiological factors for leprosy. The analytic cross-sectional study was
      carried out in one of the most hyper endemic district- Dhanusa district of Nepal.
      Stratified random sampling method was applied for the selection of the patients.
      Chi-square/Fisher's exact test was applied to assess statistically significant
      differences in values between males and females. There were 580 leprosy patients
      (385 male and 195 female) aged above 15 years registered for multi drug therapy
      between April 1, 2001 to March 31,2002 in the 16 main health centers of the
      district. Out of 580 patients, 273 patients (183 males and 90 females) were
      included in the study in order to collect the data on socio-demographics,
      patient's knowledge on leprosy, treatment seeking behaviour, and social problems
      faced by the patients. Data were collected using a structured interview schedule.
      The mean age of the male patients was 45.1 years (range 15-77 years) and female
      patients were 40.3 years (range 15-75 years). Among male patients 93.4% were
      married while among female patients 70.0% were married. Among male patients 51.9%
      were illiterate whereas 71.1% were illiterate among female patients. Most of the
      patients (69.6%) lived in joint family and the rest in nuclear family. Among male
      patients, 86.9% had good knowledge about the disease compared to 73.3% among
      females. This study showed that among the female patients 12.2% were facing high
      level of social problems, while among male patients only 4.4% were facing the
      same. About 15% patients had poor treatment seeking behaviors (8.2% among males
      and 27.8% among females). A significant gender differences among leprosy patients
      have been found in age distribution, educational status, marital status, caste
      types, family members, and overall knowledge on the general aspect of leprosy,
      social problems faced by the patients and treatment seeking behaviour.

PMID- 16295737
TI  - Study of type 2 diabetes mellitus cases at Nepal Medical College Teaching
      Hospital.
AB  - A total of 110 cases attending diabetic clinic at Nepal Medical College Teaching
      Hospital were studied. Associated risk factors and co-morbid conditions were
      analyzed. Among them 63.6% have systolic BP more than 130 mm of Hg and 24.5% have
      diastolic BP more than 85 mm of Hg reflecting hypertension as most common co
      morbid condition. Various complications of diabetes in studied subjects are
      highlighted. Eighty percent of patients have fasting blood sugar more than 110
      mg% and 93.0% have post-prandial blood sugar more than 140 mg% reflecting poor
      overall glycemic control despite the use of medication.

PMID- 16295739
TI  - A study on efficacy of lamivudine therapy in decompensated cirrhosis of liver due
      to chronic hepatitis B virus infection.
AB  - The prognosis of decompensated cirrhosis of liver resulting from chronic
      Hepatitis B Virus (HBV) infection is poor and liver transplantation is the only
      established mode of treatment. The benefits of treatment with interferon are
      outweighed by serious side effects and risks of fatal exacerbation of disease
      activity. Lamivudine rapidly reduces hepatitis B viral DNA in serum to
      undetectable levels. The purpose of this study was to evaluate effectiveness and
      safety of Lamivudine treatment in patients with advanced and end stage liver
      disease caused by Hepatitis B. This was a prospective observational study in
      which a total of 45 patients, 39 (87.0%) male and 6 (13.0%) female who had viral
      activity and child pugh score e" 8 were given Lamivudine 100 mg orally once
      daily. Among them 30 patients completed at least 6 months of therapy, majority
      (27 patients) showed improvement in liver function with decrease in serum ALT
      from mean (+/- SD) 118.8 +/- 106.5 to 50.2 +/- 57.1 U/L (p < 0.001), decrease in
      serum bilirubin from 73.9 +/- 80.5 to 44.7 +/- 62.9 micromol/l (p = 0.129),
      increase in serum albumin from 26.2 +/- 4.2 to 33.2 +/- 3.4 g/l (p < 0.05),
      decrease in prothrombin time from 8.3 +/- 4.0 to 3.9 +/- 2.9 seconds prolonged (p
      < 0.05) and reduction in child pugh score from 11.0 +/- 1.7 to 7.0 +/- 1.3 (p <
      0.001). Seroconversion was found in 5 (11.1%) patients on Intention to treat
      analysis. Among the seroconverted group, 1 (2.2%) patient also lost HBsAg. Six
      (13.0%) patient had procore mutant virus, 2 (4.4%) of them showed virological
      response. Therefore, total 7 (15.5%) patients showed virological response by
      intention to treat analysis. We conclude that inhibition of viral replication
      with Lamivudine results in a significant improvement of liver function in
      patients with decompensated cirrhosis of liver due to HBV infection.

PMID- 16295740
TI  - Comparison of needle biopsy with pleural fluid analysis for the evaluation of
      pleural lesions.
AB  - A total of 60 pleural biopsies were received at Nidaan Clinic, Kathmandu during
      the period of two years from January 2000 to December 2002. The age of the
      patient ranged from 8 years to 82 years. Male: female ratio seen was 3:1. The
      most common lesion was found to be chronic nonspecific; pleuritis seen in 50.0%
      cases followed by tuberculous pleuritis in 36.7% cases, metastatic adenocarcinoma
      in 8.3% cases, metastatic small cell carcinoma in 3.3% cases and anaplastic large
      cell carcinoma in 1.7% cases. 63.3% cases of chronic nonspecific pleuritis showed
      transudative pleural fluid effusion. None of the cases of tuberculous pleuritis
      had transudative pleural effusion. 2 cases (40.0%) of metastatic adenocarcinoma
      had transudative pleural fluid effusion which suggests the need to perform
      pleural biopsy in all the cases of transudative pleural effusion whether
      encountered for malignancy or not.

PMID- 16295741
TI  - Retrospective study of suicide cases admitted in Nepal Medical College Teaching
      Hospital.
AB  - A retrospective study of suicide cases admitted to Emergency Department and
      latter admitted to Department of Medicine and followed by Department of
      Psychiatry, Nepal Medical College Teaching Hospital. This study covered a period
      of 4 yrs. i.e. from January 2000 to December 2003. During this period total 118
      cases were admitted. Out of which 39 male and 58 female cases were studied.
      Suicide was their common motive. The most common poison was organophosphorous
      compounds. Age group of attempt suicide are between 15-45 yrs. Depression, post
      schizophrenic depression and clear psychosocial stress were important cause of
      suicide in this study.

PMID- 16295742
TI  - Renal dimensions in Nepalese population: a preliminary study.
AB  - Kidney dimensions have been measured in various parts of the world
      ultrasonographically and morphometrically though never in Nepal. Prior knowledge
      of kidney dimensions in Nepalese population would be of immense help to
      ultrasonologists planning to scan kidney. Forty normal-appearing formalin
      preserved adult kidneys of unknown age and sex were measured using a sliding
      caliper for maximum length, width and thickness. Weight of kidney was measured by
      a "micro" weighing balance. Student's t test was applied for statistical
      significance. Right kidney was 85.25 +/- 10.7mm. long, 50.65 +/- 5.8mm. wide and
      34.6 +/- 5.1 mm. thick. Left kidney was 91.65 +/- 9.2mm. long, 53.65 +/- 5.2mm.
      wide and 38.5 +/- 4.1 mm. thick. Weight of right kidney was 84.16 +/- 28.4 gm.
      and left kidney was 111.1 +/- 28.9 gm. Kidneys of Nepalese population were
      shorter and lighter than people living in other parts of the world. Difference
      between length, thickness and weight of left and right kidney was statistically
      significant but difference in width was not. Variation from other population is
      racial. Difference in left and right kidney dimensions is reported in various
      earlier literatures; therefore, Nepalese population is no exception.

PMID- 16295743
TI  - Comparative evaluation of hexokinase isoenzyme typing and antigen detection for
      differentiation of Entamoeba histolytica and Entamoeba dispar.
AB  - Entamoeba histolytica, the causative organism of invasive amebiasis is a
      potential pathogen, while asymptomatic infection is caused by E. dispar.
      Differentiation of the species is not possible on the basis of morphological
      characters by microscopic examination. In the present study an attempt has been
      made to differentiate E. histolytica from E. dispar in 45 isolates obtained from
      culture and direct stool samples respectively on the basis of hexokinase
      isoenzyme analysis and Tech Lab ELISA. A 100% correlation was found between these
      two techniques. However, Tech Lab E. histolytica antigen detection test was found
      to be both rapid and technically simple. Its use in diagnosis and epidemiological
      studies is recommended.

PMID- 16295744
TI  - Effect of Sonachandi Chyawanprash and Chyawanprash Plus--two herbal formulations
      on immunomodulation.
AB  - The immunomodulatory effects of Sonachandi Chyawanprash and Chyawanprash Plus-
      two herbal formulations have been evaluated. Both the drugs increased the
      macrophage activity and their number indicating enhancement of non-specific
      immune response and reduction of chances of infection. Besides that both
      Sonachandi Chyawanprash and Chyawanprash Plus efficiently protected Cyclosporine
      A induced immunosuppression suggesting the immunoprotective role of the aforesaid
      herbal formulations.

PMID- 16295745
TI  - Analysis of mastalgia cases presented at Manipal Teaching Hospital, Pokhara,
      Nepal.
AB  - Breast pain (Mastalgia) is a common cause of anxiety among women and frequently
      leads to a primary care clinic for consultation. This study has been designed to
      study about mastalgia cases presented at Manipal Teaching Hospital, Pokhara. A
      total of 221 female patients with breast pain presented at outpatient department
      of surgery from Jan 2000 to Dec 2001 were enrolled in this study. Overall 36.8%
      presented with cyclical mastalgia and 43.1% with noncyclical mastalgia.
      Nonhormonal therapy like reassurance, breast support, reduction in dietary fat
      intake, VitE, Vit B6 was preferred for initial therapy of mastalgia as it was
      found to be associated with improvements of cyclical mastalgia and good
      compliance. Non cyclical mastalgia mostly presented with breast lump and ended
      with excision of lump.

PMID- 16295746
TI  - Bilaterally anomalous formation and distribution of posterior cord of brachial
      plexus.
AB  - Posterior cord (PC) is formed by the union of posterior divisions of upper,
      middle and lower trunks. During routine dissection variations in the formation
      and distribution of PC and its branches were observed on both the sides. These
      variations were: i) prefixed brachial plexus on left side ii) PC on both the
      sides was formed by the union of posterior divisions of only the upper (C5, 6)
      and middle (C7) trunks while the posterior division of lower (C8, T1) trunk
      joined the radial nerve directly and also gave contribution by two roots to left
      thoracodorsal nerve iii) length of PC varied on both the sides; on right side it
      was 4cm while on left side it was 1.5cm long. iv) upper subscapular nerve on
      right side arose from PC far proximal to other branches and on its course
      communicated with lower subscapular nerve before distributing to subscapularis
      while on left side it arose from posterior division of the upper trunk (C5, 6)
      only. v) on left side nerve to teres minor arose directly from axillary nerve
      trunk instead of arising from its posterior branch. The axillary nerve on both
      the sides divided into terminal branches before entering the quadrangular space
      of arm instead after traversing the quadrangular space. vi) the branches of
      radial nerve, which normally arise in the radial groove, arose in the axilla on
      both the sides. So in cases of trauma or injury of arm some of these branches may
      be spared.

PMID- 16295747
TI  - Ocular manifestations in diabetes mellitus: an experience at Nepal Medical
      College Teaching Hospital.
AB  - A prospective study was conducted at Nepal Medical College Teaching Hospital from
      March to June 2004 to find out the ocular manifestations of diabetes mellitus. A
      total of 120 patients were included. Diabetic retinopathy was the predominant
      finding, with non proliferative diabetic retinopathy accounting for 46.5% and
      proliferative diabetic retinopathy for 0.8%. In anterior segment diseases
      cataract accounted for 38.3%.

PMID- 16295748
TI  - Prevalence of Aeromonas in different clinical and water samples with special
      reference to gastroenteritis.
AB  - A hospital based study was carried out in the Department of Microbiology,
      Tribhuvan University Teaching Hospital, Institute of Medicine with the aim to
      initiate the isolation and identification of Aeromonas spp. from the stool
      samples of gastroenteritic patients and to determine the prevalence of Aeromonas
      spp. in other clinical samples and water. Altogether 293 samples were
      investigated that include 172 stool samples, 60 pus/wound swabs, 20 body fluids
      and 41 water samples. The samples were collected and processed by standard
      microbiological techniques in order to isolate Aeromonas. Ampicillin blood agar
      (20 microg/ml) was used as selective medium for the isolation of Aeromonas. The
      specimen prevalence rate of Aeromonas spp. in stool was found to be 5.2% and the
      A. hydrophila (55.5%) was the predominant species followed by A. caviae (33.3%)
      and A. sobria (11.1%) in the stool samples. Likewise, 3.3% of pus sample showed
      positive growth of A. hydrophila. Aeromonas was not detected in any of the body
      fluids. Aeromonas spp. were isolated from 58.5% of water samples obtained from
      different hospitals. The commonest species was A. hydrophila (62.5%) followed by
      A. caviae (20.8%) and A. sobria (16.7%). In vitro susceptibility testing showed
      that the aminoglycosides and fluroquinolones were the effective antibiotics
      against Aeromonas. It was found that 88.9% of Aeromonas spp. isolated from stool
      samples were sensitive to gentamicin, 77.8% to ciprofloxacin, norfloxacin,
      tetracycline and ceftriaxone and 66.6% to nalidixic acid whereas cent percent
      Aeromonas spp. from water samples were sensitive to gentamicin, ciprofloxacin,
      norfloxacin, tetracycline and ceftriaxone and 75.0% to nalidixic acid. The
      enteric Aeromonas isolates were more resistant to antimicrobial agents than the
      water isolates.

PMID- 16295749
TI  - Admission eligibility criteria and academic success of the BSc Nursing at BPKIHS,
      Nepal.
AB  - Present study was under taken to evaluate the admission eligibility criteria and
      academic success of BSc Nursing at BP Koirala Institute of Health Sciences in
      eastern Nepal. The average BSc Nursing scores were significantly associated with
      the performance in School Leaving Certificate (SLC), Entrance, BSc I, BSc II, BSc
      III and BSc IV but not with ISc score.

PMID- 16295750
TI  - Making unsafe abortion safe: medical method.
AB  - WHO reported 13.0% of maternal deaths are related to unsafe abortion in
      developing world. To improve this, medical method of abortion has been in
      clinical use for over a decade. The antiprogestogen mifepristone followed two
      days later by a prostaglandin analogue is registered as a medical alternative to
      surgical termination of early intra uterine pregnancy. Since registration of
      medical method, research has continued to improve the medical abortion.
      Multicentre trials have shown that 200 mg of mifepristone orally and 800 ug of
      misoprostol vaginally results in a higher complete abortion percentage (95.0%).
      The gold standard method at present is 200 mg mifepristone orally followed by 800
      ug ofmisoprostol vaginally 48 hrs later gives 95.0 to 97.0% success rate. With
      much improvement and efficacy more women accept medical method for abortion with
      higher satisfaction and provide more privacy to women especially where social
      stigmas are attached to induced abortion. Use of drug is safe and non-invasive
      and training is simple and complications are minimal. This is important in
      developing world where limited trained personnels are available to perform
      surgical evacuation. The disadvantage of medical abortion is the longer duration
      of bleeding compared with surgical abortion and fear of uncertainty and side
      effects. The termination of pregnancy is legalised in Nepal now, these medicines
      could be made available in market.

PMID- 16295751
TI  - Vascular tumours disguising as solid organ injuries on computed tomography: a
      report of two cases.
AB  - We report two cases of uncommon vascular lesions (Littoral cell angioma and liver
      haemangioma) mimicking traumatic organ injuries. The patients' histories and
      clinical findings of trauma were well demonstrated. Both patients had interesting
      CT scan features that were suggestive of solid organ injuries. However, both
      conditions were subsequently found to be benign incidental lesions.

PMID- 16295752
TI  - Allergic bronchopulmonary aspergillosis--a case report.
AB  - A 24 years old male presented with recurrent symptoms of cough and breathlessness
      for 6 years but increased in past 6 months. Fleeting radiological opacities,
      peripheral eosinophilia and central type bronchiectasus in high resolution CT
      scan gave the suspicion of allergic bronchopolmonary aspergilosis. Confirmation
      of the diagnosis was done by skin prick and immunological tests. The patient
      showed an excellent response to oral prednisolone.

PMID- 16295753
TI  - First case of Dengue virus infection in Nepal.
AB  - Dengue virus transmitted by Aedes mosquito is one of the important cause health
      problems in world. Dengue fever and more severe and often fatal forms namely
      dengue hemorrhagic fever and dengue shock syndrome are emerging health problems
      in many part of the globe. No cases of Dengue virus infection have been reported
      from Nepal till date and for the first time, we report a case of dengue fever
      from Nepal.

PMID- 16295754
TI  - [About the tributaries of the arch of great saphenous vein. Concerning 40
      dissections].
AB  - The arch of the great saphenous vein cross receives numerous tributaries from the
      abdominal wall, male external genitalia and pelvic limbs. These collaterals
      present many variations relating to their number and mode of anastomosis. Their
      misappreciation may lead to post operative recurrences after surgical treatment
      of varices. For a last study of these variations, we dissected 40 inguinofemoral
      regions in fresh black african corpes. The conventional type in a "vein strar"
      shape was present in 4 cases. An abdominal common vein produced through the
      merging of the superficial epigastric and superficial circumflex iliac veins was
      found in 5 cases. A genital common vein summarising the external pudendal veins
      was present in 19 cases. In 8 cases the abdominal and genital common vein was
      simultaneously present. An anterior saphenous vein was found in 15 cases, and a
      posterior saphenous vein in 5 cases. These results, confirm the importance of
      anatomic variations. Their knowledge is necessary to avoid recurrences after
      surgery of varicose veins.

PMID- 16295755
TI  - [Physical performance and thermoregulatory study of subjects with sickle cell
      trait during a sub-maximal exercise].
AB  - The sickle cell trait is a genetic abnormality of red blood cells. It is due to
      the mutation of a parental gene, which rest Its to the substitution of glutamic
      acid by valin on beta globin chain of haemoglobin. The possibility for sickle
      cell trait carriers (SCT) to present any disturbance during predominantly
      anaerobic and aerobic exercises is unclear. Ten (10) subjects with sickle cell
      trait and 10 subjects control were studied during exercise test on
      cycloergometer. They were all students of the National Institute of Popular
      Education and Sport of Dakar. The mean of environmental temperature was 26
      degrees C and humidity was 60 to 80%. After haematological analysis, a submaximal
      muscular exercise for one hour with 75% of maximal heart rate was done. We have
      determined heart rate, blood pressure, rectal and skin temperature during
      exercise. Haematological parameters shown any significant difference between the
      two groups. No significant difference was found in cardiocirculatory variables
      during maximal exercise in cycloergometer between control group and sickle cell
      trait group. The two groups have done submaximal exercise during 1 hour without
      particular difficulty. We have not observed a significant difference between the
      two groups in cardiovascular variables, rectal and skin temperature during
      exercise, and after 3 minutes of rest. These results show that subjects with SCT
      have physical capacity comparable with control subjects during a sub maximal
      exercise for 1 hour. We can assure that subjects with SCT in our country may
      participate in sports competition, as well as normal subjects (HbAA).

PMID- 16295756
TI  - [Pyoderma gangrenosum in dakar: about 14 cases].
AB  - From January 1990 to December 2001, we undertook a retrospective study in the
      dermatology department of Aristide le Dantec hospital in order to assess the
      epidemiologic, clinical and evolutionary profiles of pyoderma gangrenosum (P.G).
      All files of patients diagnosed with PG were reviewed. The diagnosis was based on
      clinical and histological aspects. Fourteen files of patients with PG were
      reviewed. They were constituted of 8 males and 6 females, with a median age of
      24.5 (extreme 4 and 54 years). Paediatric forms represented 30 % of the cases.
      The typical aspect with an ulceration with elevated edge comprising of purulent
      hutchs was observed in all the cases. The localization on the level of the lower
      limbs was noted among 12 patients (85.7 %). The PG was associated to chronic
      ulcerative colitis (1 case), rheumatoid spondylitis (1 case) and rheumatoid
      arthritis in all cases. After 11 weeks treatment by oral corticotherapy at the
      daily posology of 1 mg/kg/, cicatrization of cutaneous lesions were noted in all
      the cases. Five reccurences were observed. P.G remains a rare pathology with no
      difference on races and regions . this is particularly true on children. Our
      serie, is remarkable by the high frequency of its paediatric forms. As for
      clinical and evolutive aspects as well as associated pathologies, findings are
      comparable with those described other series

PMID- 16295757
TI  - [Prevalence and morbidity of G6PD deficiency in sickle cell disease in the
      homozygote].
AB  - Sickle cell disease and G6PD deficiency have similar prevalence of 8 to 10% in
      Senegalese population. Our objectives were to determine the prevalence of G6PD
      deficiency in Hb S carriers and normal subjects, and to assess the interaction of
      G6PD deficiency on clinical severity of sickle cell disease. G6PD activity was
      measured in 319 sickle cell patients and in 318 subjects without HbS. Clinical
      severity was compared in male homozygous sickle cell patients (11 with G6PD
      deficiency and 19 without deficit). In homozygous sickle cell patients, the G6PD
      status was assessed after correction of reticulocyte count following the micro
      centrifugation method of Herz. We found that prevalence of G6PD deficiency was
      higher in sickle cell disease patients (21.6 %) than in normal subjects (12.3 %)
      (p = 0.001). No difference was found in the two groups of male sickle cell
      disease patients concerning number of vaso-occlusive crisis, number of
      transfusion, frequency of infectious episodes, number of chronic complications,
      disturbances on patient's activity and total index severity.

PMID- 16295758
TI  - [Thoracic and thoraco-lumbar discs herniations: diagnosis and therapeutic
      management].
AB  - Summary Management of symptomatic thoracic disc hemiations is difficult because
      of their polymorphic symptomatology and hardness to join the intervertebral
      thoracic disc surgically. The objective of this study was first to show the
      difficult diagnosis of these discal herniations and their posterior approach
      particularities; secondly, to analyse our results and compare them with those of
      the literature. This retrospective study analyses a four patients series operated
      between January 1997 and march 2003 using intraoperative somatosensory evoked
      potentials. All of them had before surgical management, a lumbar Xray or a MRI.
      The average postoperative follow-up was seven months. All patients were males
      with a mean age of 39.5 years old (extremes: 22-59). They had systematisation of
      their lumboradiculalgia, leading to an average delayed diagnosis of 10 months.
      The disc herniation was paramedian in three cases, median in one,. It was in T10
      T11 in one case, in T11-T12 in two and in T12-L1 in one. All the patients were
      operated on with a posterior approach, recording the intraoperative somatosensory
      evoked potentials. Disc herniation was resected in three cases. Functional
      results were satisfactory (no pains for three patients) in the follow-up period
      of seven months. Every patient presenting with an atypical lumboradiculalgia must
      have a spine MRI to diagnose the symptomatic thoracic disc herniation. Surgery
      has good results if technical details are used respecting the threatened spinal
      cord.

PMID- 16295759
TI  - [Expression of proliferation marker Ki 67 in chronic lymphocytic leukemia].
AB  - Chronic lymphocytic leukemia (CLL) is characterized by a clonal expansion of low
      proliferating mature B and T lymphocytes in the bone marrow and peripheral blood.
      The nuclear antigen Ki 67 is a protein detected in G1, S, G2 and M phases of the
      cell cycle, but not in G0, and thus, is a widely accepted proliferation marker of
      Human tumors. The aim of this study was to evaluate Ki 67 monoclonal antibody in
      CLL. We studied 48 patients diagnosed as CLL on the presence of clinical signs,
      over 4.109/l circulating lymphoid cells and immunophenotyping by flow cytometry
      using CD19, CD5, CD22, CD23, FMC7 and immunoglobulin light chains monoclonal
      antibodies. Ki 67 immunostaining was determined by Avidin Biotin Complex method.
      Our results allows to characterize between CLL: one group which proliferation
      rate (percentage of Ki 67 positive cells) was equal or less than 2%, represented
      by 14 cases (29,2%) with morphological aspect of typical CLL, one group which
      proliferation rate was between 3% and 9% represented by 32 cases (66,6%) with
      morphological aspect of polymorph CLL or prolymphocytic leukemia, and a last
      group with proliferation rate equal or up to 10% and corresponding to two cases
      (4,2%) of transformation of CLL to high grade Non Hodgkin lymphoma. There were no
      correlation between Matutes immunological score and proliferation rate, as this
      rate was 2.9% in score < 3 and 2.7% in score > 3. This study confirm the Ki 67
      usefulness in studying cellular proliferation, and underline that CLL with
      polymorphic cytology are more proliferate than typical CLL. These data reinforce
      the notion that CLL is a disease with heterogeneity in clinical behavior,
      immunophenotype, cytogenetic, molecular aspects, and thus, prognostic.

PMID- 16295760
TI  - [A case report of intrapelvic foetal osseous remains localization after
      clandestine caused abortion].
AB  - A 26 year old women, unmarried, second gesture, primiparous, had been
      hospitalized in our departement for the management of a hypogastric mass.
      Ultrasonography had shown: an uterus of normal size, a normal uterine vacuity
      line with presence of many osseous and fibrous constituents inside the inter
      vesico-uterine area, including one femoral osseous of 18,6 mm corresponding to 15
      weeks of amenorrhoea. A few months before, the patient had undergone a
      clandestine caused abortion on a progressive intrauterine pregnancy of 12 weeks
      of amenorrhoea certified by ultrasonography. It is an exceptional complication of
      clandestine caused abortion. It gives the opportunity to us to discuss its
      etiopathogenic mechanism. It also enables us to point out the complications of
      the clandestine caused abortion and to insist on the need for its prevention.

PMID- 16295761
TI  - [Acute chloroquine poisonning in Le Dantec Teaching Hospital].
AB  - Chloroquine poisoning is an acute severe drug induce entity increasingly frequent
      in Senegal. This is due on one hand to its easy accessibility and its
      conditioning, on the other hand to its frequent use, in the voluntary attempt of
      ending pregnancy. The aim of this study is to assess the frequency and the
      severity of such poisoning in a senegalese intensive unit care. We undertook a
      descriptive retrospective study from January 1998 to December 2003 in the
      intensive care unit of Aristide Dantec Hospital. All patients admitted for
      voluntary or accidental acute intoxication to chloroquine were included. The
      parameters studied were: reason of admission, alledged ingested amount, delay of
      admission, hemodynamic modifications, therapeutic data and evolution. During the
      study period, forty-nine cases of chloroquine intoxication were listed out of 239
      acute intoxications. Among these 49 cases, 16 files were not processable. These
      accounted for 1,48% of all admissions during this period. Women were more
      represented (78.78%). In 90.90% of the cases, the intoxication was voluntary,
      they were related to suicidal attempt in 57.57% of the cases. The willingness to
      end a course of a pregnancy was found in 33.33% of the cases. The average age was
      22.69 years (11 years - 38 years). The average time of admission was 4 hours.
      with extremes of 1 and 8 hours. The clinical symptoms were dominated by
      hemodynamic, neuropsychiatric and respiratory disorders. Toxicological analysis
      was not carried out. Ionic disorders were dominated by hypokaliemies and
      electrocardiographic disorders by a widening of QRS. Symptomatic treatment
      systematic, was based on a vascular filling and the use of adrenalin. evacuation
      treatment consisted of a systematic gastric "lavage" and the use of activated
      charcol on (3.03%). Diazepam as treatment antidotic was seldom used. Psychiatric
      consultation was systematically carried out. Total mortality was 6%. The authors
      emphasize the necessaty to: Inform the population on the absence of drugs being
      able to stop a pregnancy. Think on the urgency need to implement a medical
      emergency and reanimation departments (SMUR). Create poison control centers in
      Senegal.

PMID- 16295762
TI  - [Healing activity of methanolic extract of the barks of Spathodea campanulata
      Beauv (Bignoniaceae) in rat experimental burn model].
AB  - Spathodea campanulata Beauv. (Bignoniaceae) is widely distributed through Africa
      and found in particular in Cameroon and Senegal. It is used in traditional herbal
      medicine for the treatment of ulcers, filaria, gonorrhea, diarrhea and fever. S.
      campanulata was also known in Cameroon traditional medicine to have a healing
      activity in burn wounds. The aim of the present study was to assess the burn
      healing effectiveness of the methanolic extract of the barks of S. campanulata
      ointment (MEBSCO) in comparison to those of Centella asiatica and Peru's balm in
      experimental burn model in rats. Experimental burn was made in rat under chloral
      anaesthesia with electric iron (200 degrees C) on the right and left side of the
      medianus line. Topical applications of MEBSCO (2%, 10% and 49%) dose-dependently
      decreased the score damage of the burn site. Treatment with 10% and 49% of MEBSCO
      varied the score damage from 5 to 1 +/- 0.4 and 5 to 0.2 +/- 0.5 (p < 0.05, n =
      5) respectively, at day 15 after experimental burn. As well as C. asiatica (1%)
      and Peru's balm (1%) ointments, MEBSCO (10% and 49%) induced a complete burn
      healing on the 19-20th post burn day. This study shows for the first time, the
      burn healing effectiveness of MEBSCO in experimental burn model. It also provides
      a rational use of the S. campanulata barks in traditional medicine to promote
      burn healing.

PMID- 16295764
TI  - [Sexual child abuse: correlation between medical certificates' conclusions and
      judiciary sanctions].
AB  - Sexual child abuse, comprises of indecency attitudes and physical misbehaviours,
      directed towards children are dominated by rape. The objective of our study was
      to assess in sexual child abuse the relation between the conclusion of medical
      certificates and court decision. It is a retrospective study carried out from
      1994 to 1998 on the clerk's office correctional repertories in Dakar regional
      court. An overall number of 79 cases of child abuse were collected in 5 years
      period. Children under 18 years old of of both sex, were concerned. Data found
      were correlated with a review of requisition cases received by the of gynaecology
      and obstetrics clinic of Aristide Dantec Hospital. This facilitates the
      establishement of the relationship between the offences and the pronounced
      sanctions, as well as the initial medical certificate and these sanctions. The
      sanctions were severe whenever rape had been retained. Some cases were
      disqualified in indecent assault and were judged as such. The judge decision,
      which follow the medical certificate conclusions in 11 cases out of 14 shows the
      importance and reliability of this medical document. All files reviewed at the
      medical and legal level were incomplete. The difficulty of the materiality of the
      rape and the psychological consequences in the long run and especially HIV
      infection should invite to a multidisciplinary, specialized and organized
      management of sexual child abuse. This study has shown the importance of a
      correct and complete drafting of the medical certificate, to enable the
      establishment by the judge the materiality of the facts.

PMID- 16295763
TI  - [Liver arterial ischemia after cephalic pancreatico-duodenectomy. A case report].
AB  - Cephalic pancreaticoduodenectomy is the best treatment for cephalic pancreas
      cancers. A rare complication is the liver ischemia after the divison of
      gastroduodenal artery. This complication can occur when a celiac trunk stenosed
      by the median arcuate ligamentous is not recognised. We report the case of a 40
      old woman who underwent cephalic pancreaticoduodenectomy for an adenocarcinoma of
      pancreas head. There was no complication immediatly. Two weeks later, she
      presented two episodes of angiocholitis. An abdominal tomodensitometry showed a
      liver arterial ischemia associated with a celiac trunk stenosis. There was a left
      hepatic artery wich came from the left gastric artery. Medical treatment of the
      angiocholitis was successful. Surgical revascularization was not necessary. Nine
      months after, arterial revascularization by the left hepatic artery and
      biological hepatic tests were restored. This case report talks about the
      importance of angioscanner before pancreatic surgery when celiac and mesenteric
      angiography is not available. Also, it underlines the importance of the
      gastroduodenal artery occlusion test before his ligation during
      pancreaticoduodenectomy.

PMID- 16295765
TI  - [Dakar physicians' therapeutic attitude towards non complicated peptic ulcer
      disease].
AB  - Peptic ulcer disease is topic of guidelines in developed countries. In South
      area, without consensus conference, physicians' attitude towards this disease is
      varied. So, we aimed to describe therapeutic decisions of physicians in Dakar,
      regarding literature and the role of Helicobacter pylori in gastro-intestinal
      diseases. From 2001 december first to 2002 January 31, a survey was made in a
      sample of 171 physicians in Dakar with a questionnaire. All generalists,
      internists and gastroenterologists working in public or private health places of
      Dakar were concerned. The rate of responses was 68%. 65.5% of physicians had not
      read guidelines about peptic ulcer disease and H. pylori but 89% of them had read
      articles on these topics. Most of the physicians (76%) ordered systematically or
      mainly treatment to eradicate H. pylori. 95% of them did not require proof of
      infection before treatment. Association of gastric antisecretory drug with
      amoxicillin and metronidazole was mostly used (77.5%). Double dose of
      antisecretory drug was prescribed by 51.5% of physicians. For 40.5% of them, the
      duration of treatment was 7 days while 53.5% prolonged duration to 10 or 14 days.
      Complementary antisecretory drug was systematic for most of physicians (83.5%).
      These multiple therapeutic options, sometimes not in accordance with
      recommandations, militate in favour of more intensive participation of Dakar
      physicians to scientific meetings, in order to rationalize their therapeutic
      attitude towards peptic ulcer disease and take into account local data.

PMID- 16295766
TI  - As plans improve efficiency, growth in admin costs plummets.

PMID- 16295767
TI  - California IPA reports dazzling performance under capitation.

PMID- 16295768
TI  - Minnesota's capitated programs break open risk adjustment process.

PMID- 16295770
TI  - Hospital LOS still declining, but huge variations exist across diagnoses.

PMID- 16295769
TI  - Do older adults in capitated plans have higher rates of eye disease?

PMID- 16295771
TI  - The classical origins of Pavlov's conditioning.
AB  - This article presents a brief description of the scientific discovery of
      classical conditioning both in the United States and in Russia. The incorporation
      of classical conditioning as a scientific method in the United States is
      described. Particular attention is given to how and why the terminologies used to
      identify the components of classical conditioning were modified over the years. I
      then trace the curious evolution of the terminology associated with Pavlov's form
      of conditioning, from its introduction to the United States as "the Pawlow
      salivary reflex method" to its present appellation as classical conditioning.
      Finally I conclude by developing a theory as to when and why the term classical
      conditioning was adopted.

PMID- 16295772
TI  - Fear develops to the conditioned stimulus and to the context during classical
      eyeblink conditioning in rats.
AB  - In classical eyeblink conditioning, non-specific emotional responses to the
      aversive shock unconditioned stimulus (US), which are presumed to coincide with
      the development of fear, occur early in conditioning and precede the emergence of
      eyeblink responses. This two-process learning model was examined by concurrently
      measuring fear and eyeblink conditioning in the freely moving rat. Freezing
      served as an index of fear in animals and was measured during the inter-trial
      intervals in the training context and during a tone conditioned stimulus (CS)
      presented in a novel context. Animals that received CS-US pairings exhibited
      elevated levels of fear to the context and CS early in training that decreased
      over sessions, while eyeblink conditioned responses (CRs) developed gradually
      during acquisition and decreased during extinction. Random CS-US presentations
      produced a similar pattern of fear responses to the context and CS as paired
      presentations despite low eyeblink CR percentages, indicating that fear
      responding was decreased independent of high levels of learned eyeblink
      responding. The results of paired training were consistent with two-process
      models of conditioning that postulate that early emotional responding facilitates
      subsequent motor learning, but measures from random control animals demonstrate
      that partial CS-US contingencies produce decrements in fear despite low levels of
      eyeblink CRs. These findings suggest a relationship between CS-US contingency and
      fear levels during eyeblink conditioning, and may serve to clarify further the
      role that fear conditioning plays in this simple paradigm.

PMID- 16295773
TI  - Discrete and contextual cue alterations eliminate the instrumental appetitive-to
      aversive transfer impairment in phenytoin-treated rats.
AB  - We have shown previously that the antiepileptic phenytoin impairs transfer in an
      instrumental learning task (Banks et al., 1999). The present study examined the
      effects of contextual alterations on appetitive-to-aversive transfer performance
      of rats treated with either phenytoin or tang. Adult rats were tested in tone
      signaled appetitive and aversive instrumental tasks, where the animal bar-pressed
      to obtain a food reward (sugar pellet) or to avoid shock. Rats were trained on
      the appetitive task for 31 days. Beginning on the twenty-first day, rats were
      gavaged with either phenytoin or tang twice daily. Animals were then transferred
      to aversive training, with the phenytoin or tang treatment continuing throughout
      the 25 testing days. For some animals, contextual changes were introduced as they
      shifted from appetitive to aversive training, while for other animals these
      changes were not made. Phenytoin-treated rats that were presented with changes in
      context as they transferred from the appetitive to the aversive task learned the
      avoidance response to levels substantially higher than drug-treated rats not
      presented with the contextual changes. These results indicate that phenytoin
      impairs avoidance learning following transfer from the appetitive task, and that
      this impairment can be eliminated by introducing changes in context at the point
      of transfer. In the tang-treated control subjects, on the other hand, there was
      no improvement in transfer learning performance associated with the changes in
      contextual cues. This pattern of results suggests that contextual encoding
      processes in rats being trained in an instrumental appetitive-to-aversive
      paradigm are dramatically affected by phenytoin.

PMID- 16295774
TI  - Amygdala and periaqueductal gray lesions only partially attenuate unconditional
      defensive responses in rats exposed to a cat.
AB  - Defensive responses to a cat were observed in rats given excitotoxic lesions of
      the central nucleus of the amygdala (ACe), dorsolateral periaqueductal gray
      (dlPAG), ventral periaqueductal gray (vPAG), or sham lesions. Rats were placed
      adjacent to a compartment containing a cat. Sham-lesioned rats avoided the area
      nearest the cat and preferred the area furthest away from the cat. They also
      exhibited numerous defensive responses including, climbing, escape from the
      apparatus, and freezing. Rats with lesions of the ACe reacted like the sham
      lesioned rats by preferring the area of the apparatus furthest from the cat,
      however they climbed and escaped significantly less than sham lesioned rats.
      Avoidance of the area adjacent to the cat was attenuated in rats with lesions of
      the vPAG. Climbing along the walls of the apparatus was also attenuated in rats
      with lesions of the vPAG. Escapes from the apparatus were not significantly
      reduced by lesions of the vPAG and dlPAG. Thus, ACe lesions attenuated climbing
      and eliminated escapes, but did not impair locomotion of the rat away from the
      cat.

PMID- 16295775
TI  - Effects of lipopolysaccharide on consolidation of partial learning in the Y-maze.
AB  - Research on consolidation of long-term memory suggests that acute immune system
      activation induced by endotoxin lipopolysaccharide (LPS) may disrupt
      consolidation of newly acquired learning. Adult male Sprague-Dawley rats were
      trained to perform a simple Y-maze task and were immediately afterwards
      administered LPS (15 microg/kg) or saline. After a seven-day interval, subjects
      were returned to the Y-maze and were retrained to criterion. It was found that
      subjects treated with saline required significantly fewer trials to relearn the
      task relative to the LPS group and a no-partial-learning control group, which
      themselves did not differ. These results are most readily explained in terms of a
      disruptive effect of acute immune system activation on consolidation of newly
      induced acquired memories.

PMID- 16295776
TI  - Clinicopathologic significance of gastric and intestinal phenotypic marker
      expression in gastric carcinomas.
AB  - BACKGROUND: It is well known that both gastric and intestinal phenotypic cell
      markers are expressed in gastric cancers. This study was aimed at investigating
      the correlation between gastric and intestinal phenotypic marker expression
      patterns of tumors and the clinicopathologic characteristics of gastric
      carcinomas. METHODS: We evaluated phenotypic marker expression by
      immunohistochemical staining with monoclonal antibodies. All tumors were
      classified as gastric (G), gastric and intestinal mixed (GI), intestinal (I), or
      null (N) phenotype. RESULTS: The tumors were phenotypically divided into G
      phenotype tumors (33.2%), GI-phenotype tumors (25.7%), I-phenotype tumors
      (26.8%), and N-phenotype tumors (14.3%). N-phenotype tumors were associated with
      more corporeal location than GI- and I-phenotype tumors (o=0.009 and p=0.007,
      respectively), a larger size than I-phenotype tumors (0=0.007), a higher
      proportion of advanced gastric cancers than G-, GI-, and I-phenotype tumors
      (0=0.003, p<0.001, and p<0.001, respectively), more perineural invasion than G-,
      GI-, and I-phenotype tumors (p=0.076, p=0.003, and p=0.003, respectively), and
      more lymph node metastasis than GI-phenotype tumors (p=0.017). I-phenotype tumors
      were associated with a higher proportion of intestinal-type tumors than G-, GI-,
      and N-phenotype tumors (p<0.001, p=0.011, and p<0.001, respectively). CONCLUSION:
      Our results indicate that the gastric and intestinal phenotypic marker expression
      pattern of tumors is prognostically useful for patients with gastric carcinoma.

PMID- 16295778
TI  - Irinotecan, continuous 5-fluorouracil, and low dose of leucovorin (modified
      FOLFIRI) as first line of therapy in recurrent or metastatic colorectal cancer.
AB  - BACKGROUND: Irinotecan, in combination with 5-fluorouracil (5-FU) and a high dose
      of leucovorin (LV), known as FOLFIRI regimen, has shown activity in recurrent or
      metastatic colorectal cancer. Therefore, we evaluated the efficacy and safety of
      irinotecan, 5-FU and a low dose of LV (modified FOLFIRI) as a first line of
      therapy for patients with relapsed or metastatic colorectal cancer. METHODS:
      Between January 2002 and October 2004, 44 patients with histologically confirmed
      recurrent or metastatic colorectal cancer were enrolled. The chemotherapy regimen
      schedule consisted of 180 mg/m2 of irinotecan being administered intravenously
      (i.v) on Day 1, 400 mg/m2 of 5-FU via i.v bolus with 600 mg/m2 of continuous
      infusion for 22 hrs on both Day 1 and 2, and 20 mg/m2 of leucovorin on both Day 1
      and 2 , repeated every two weeks. RESULTS: The overall response rate was 47.8%.
      Of the 40 evaluated patients, one had CR (2.3%) and 20 had PR (46.5%). Toxicities
      were mild and easily manageable. Three patients experienced 23 episodes of Grade
      3/4 leukopenia., Only one patient developed Grade 3/4 diarrhea. None experienced
      Grade 3/4 thrombocytopenia. CONCLUSION: Modified FOLFIRI with a low dose of LV is
      an effective and tolerable regimen for patients with recurrent or metastatic
      colorectal cancer.

PMID- 16295777
TI  - Expression of Cyclooxygenase-2 and Bcl-2 in human gastric adenomas.
AB  - BACKGROUND: Cyclooxygenase (COX)-2 is the rate-limiting enzyme in prostaglandin
      synthesis. An increased expression has been implicated in the development and
      progression of human gastric cancers and colorectal adenomas and cancers. This
      study aimed to determine the involvement and association of COX-2 and Bcl-2 in
      precancerous gastric adenomas. METHODS: Seventy-nine gastric polyps were obtained
      by endoscopic mucosal resection or polypectomy from January, 2000 to July, 2003.
      Immunohistochemical expression of COX-2 and Bcl-2 was observed, and their
      relationships with various clinicopathological factors were analyzed. RESULTS:
      Histologically, 13 hyperplastic polyps and 66 tubular adenomas, of which 17
      showed high-grade dysplasia, were observed. Increased COX-2 expression was
      observed in low-grade and high-grade tubular adenomas compared to hyperplastic
      polyps (p=0.004 and p=0.001, respectively). COX-2 expression was significantly
      higher in larger (>1 cm) compared with smaller (<1 cm) tubular adenomas
      (o=0.034), but no relation was observed in hyperplastic polyps. While Bcl-2
      expression differed significantly according to histology, increased Bcl-2
      expression was observed especially in COX-2 positive low-grade tubular adenomas.
      CONCLUSION: COX-2 expression increased in a size-dependent manner in tubular
      adenomas, suggesting a role in polyp growth. The increased expression of Bcl-2 in
      tubular adenomas, especially in COX-2 positive tubular adenomas, suggests that
      COX-2 action may be related to Bcl-2 expression.

PMID- 16295779
TI  - The inverse association between the presence of antibody to hepatitis B surface
      antigen and atopy in young adults.
AB  - BACKGROUND: Some bacterial and viral infections may reduce the risk of atopy, and
      this is based on the concept of their ability to divert the immune system towards
      the Th1 responses. Most of the hepatitis B virus (HBV) infections occur in the
      developing countries and this is where atopic disorders are least prevalent. Th1
      responses are important for the viral clearance of HBV and also for antibody
      production. The aim of the study is to investigate whether the presence of
      antibodies to the hepatitis B surface antigen (anti-HBs) is inversely associated
      with atopy in adults. METHODS: A random sample of 358 subjects, who were without
      hepatitis B surface antigen, was recruited; they were aged from 18 to 79 years
      (105 young adults aged <40 years and 253 older adults aged > 40 years).
      Determinations of the anti-HBs and skin prick tests using aeroallergens were
      performed. Those subjects with one or more positive skin reactions (a mean wheal
      diameter 23 mm) were considered atopic. RESULTS: The prevalence rate of atopy
      (p=0.035) or the sensitization to Dermatophagoides farinae (p=0.01) was
      significantly lower in the subjects with anti-HBs than in those subjects without
      anti-HBs for the young adults, but not for the older adults. The logistic
      regression analysis that was done on the young adults showed that the presence of
      anti-HBs was associated with a significantly lower risk of atopy (the odds ratio
      adjusted for confounding variables = 0.40 [95% CI 0.16-0.981, p=0.046) or with
      the sensitization to D. farinae (0.20 [0.06-0.65], p = 0.008). CONCLUSION: The
      presence of anti-HBs produced by a natural HBV infection or vaccination might be
      inversely associated with atopy in young adults.

PMID- 16295780
TI  - Effect of high-dose intravenous N-acetylcysteine on the concentration of plasma
      sulfur-containing amino acids.
AB  - BACKGROUND: The purpose of this study was to determine the adequate loading and
      maintenance doses of N-acetylcyseteine (NAC) for patients suffering from acute
      ROS-induced injury. METHODS: Concentrations of extra cellular NAC, cysteine
      (Cys), cystine (Cyst2), and methionine (Met) were measured in vitro, at which
      more than 50% of the intracellular ROS raised by paraquat were suppressed using
      Swiss 3T3 fibroblasts. An in vivo pharmacokinetic study followed on a healthy
      subject to determine the proper loading and maintenance doses of reduced NAC
      following intravenous administration of 25 mg/kg NAC. RESULTS: In vivo, NAC
      suppressed ROS in a dose dependant manner. 10 mM of NAC suppressed about 50% of
      ROS, and was comparable to 10 microM of Cys and Met and 400 microM of Cys2. In
      vitro, the elimination of half life was achieved at 2.88+/-1.14 h for NAC and at
      3.68+/-1.84 h for total NAC. The body clearances were 1.23+/-0.77 L h(-1) kg(-1)
      and 0.56+/-0.27 L h(-1) kg(-1) and the volumes of distribution were 3.07+/-0.10 L
      kg(-1) and 3.00+/-0.11 L kg(-1), respectively. The loading and maintenance NAC
      doses used to reach the target concentration of 10 mM, were 5010 mg. kg(-1) and
      2250 mg min(-1) kg(-1), respectively CONCLUSION: NAC provides an antioxidant
      effect on ROS produced by paraquat in vivo. However, in vitro, our results showed
      that the intravenous NAC dose could not be estimated from NAC plasma
      concentration or its metabolites.

PMID- 16295781
TI  - High-dose versus low-dose cyclophosphamide in combination with G-CSF for
      peripheral blood progenitor cell mobilization.
AB  - BACKGROUND: To compare the mobilizing effects and toxicities of two different
      doses of cyclophosphamide (CY) plus lenograstim (glycosylated G-CSF), we
      performed a prospective randomized study by enrolling patients suffering with
      either high-risk Non-Hodgkin's lymphoma (NHL) or breast cancer undergoing
      ablative chemotherapy. METHODS: The NHL patients received 4 cycles of CHOP and
      the breast cancer patients received 2-3 cycles of FAC (FEC) adjuvant
      chemotherapy. Then, the patients were randomly allocated to receive CY 4 g/m2
      (arm A) or 1.5 g/m2 (arm B) in combination with lenograstim. Large volume
      leukapheresis was carried out and it was continued daily until the target cell
      dose of 2 x 10(6) CD34+ cell/kg was reached. RESULTS: Twenty-seven patients were
      enrolled in the study. The median number of leukaphereis sessions actually
      performed was 2.5 sessions in arm A and 3 sessions in arm B. The target cell dose
      was obtained with the median number of one leukapheresis session in both arms of
      the study (p=0.09). The collected number of CD34+ cells in the leukapheresis
      products was higher in arm A than arm B (22.4 vs. 9.9 x 10(6)/kg, respectively,
      p=0.05). Grade III or IV leukopenia was present in 14/15 patients (94%) in arm A
      and in 1/12 patients (8%) in arm B (p<0.0001). Grade Ill or IV thrombocytopenia
      was present in 8/15 patients (54%) in arm A, but this was not present in any
      patients of arm B (p=0.0004). Neutropenic fever occurred in 6/15 patients (40%)
      in arm A, and in 1/12 patients (8%) in arm B (p=0.09). The hematological recovery
      of the leukocytes and platelets after transplantation was not statistically
      different between the two doses. CONCLUSION: Low-dose CY plus lenograstim is a
      safe and effective mobilizing regimen.

PMID- 16295782
TI  - Lack of association of glutathione S-transferase P1 Ile105Val polymorphism with
      aspirin-intolerant asthma.
AB  - BACKGROUND: Glutathion S-transferase P1 (GSTP1), the abundant isoform of
      glutathione S-transferase in lung epithelium, plays an important role in cellular
      protection against oxidative stress and toxic foreign chemicals. GSTP1
      (Ile105Val) polymorphism has been reported to be associated with asthma related
      phenotypes such as atopy and bronchial hyperresponsiveness. Therefore we
      investigated whether this polymorphism may be associated with the development of
      aspirin-intolerant asthma (AIA). METHODS: GSTP1 Ile105Val polymorphism was
      determined using a single based extension method in 88 AIA subjects and compared
      to 154 aspirin-tolerant asthma (ATA) subjects and 119 normal healthy controls
      (NC) recruited from the Korean population. RESULTS: No significant differences in
      allele and genotype frequencies of the GSTP1 Ilel105Val polymorphism were
      observed in the three groups (p>0.05). However, minor G allele frequency of the
      GSTP1 Ilel105Val polymorphism in AIA group (16.5%) tended to be lower than in the
      NC group (20.6%). CONCLUSION: These results suggest a lack of association of the
      GSTPI Ilel105Val gene polymorphism with AIA phenotype in the Korean population
      [word count: 159].

PMID- 16295784
TI  - Delayed ventricular septal rupture after percutaneous coronary intervention in
      acute myocardial infarction.
AB  - In the era before reperfusion therapy, ventricular septal rupture complicated
      1approximate3% of acute myocardial infarctions (AMI) usually 3-5 days after
      onset. Studies have reported a positive correlation between the incidence of
      septal perforation and total occlusion of the coronary arteries. A 70-year old
      female patient was referred to the emergency room with the diagnosis of acute
      anterior myocardial infarction (MI) and recent cerebral infarction. The coronary
      angiogram showed a 90% stenosis at the mid-portion of the left anterior
      descending artery (LAD), and the lesion was successfully treated by percutaneous
      coronary intervention (PCI) with stent implantation. After PCI, the anterior wall
      motion improved on the follow-up echocardiogram. However, on the 20th hospital
      day, the patient condition deteriorated suddenly with pulmonary congestion. The
      echocardiography revealed a 1.3 cm ventricular septal defect at the apical septum
      with a left-to-right shunt. We report this rare case of delayed septal rupture in
      a patient with patent LAD after PCI and recovery of wall motion.

PMID- 16295783
TI  - Double autologous stem cell transplantation for multiple myeloma: a Korean single
      center study.
AB  - BACKGROUND: Although high dose chemotherapy coupled with an autologous stem cell
      transplantation (ASCT) is widely accepted as effective therapy for multiple
      myeloma (MM), few reports are available in Korea, especially in the area of
      double ASCT. We present the results of an institutional retrospective study of 12
      patients with MM treated by double ASCT. METHODS: Eligible patients received
      induction therapy using vincristine, adriamycin, dexamethasone (VAD), and
      mobilization was performed using cyclophosphamide plus lenograstim. High-dose
      melphalan (total 200 mg/m2) was used to condition the ASCT. RESULTS: The median
      interval from diagnosis to ASCT was 6 months (range, 1.8-15.3 months). The median
      interval between the 1st and 2nd ASCT was 4.4 months (range 2.1-48.7 months). The
      median follow up was 18.3 months (range 8.1-50.5 months) for the nine surviving
      patients. No therapy-related mortality occurred. Following induction
      chemotherapy, two patients experienced CR. Following double ASCT, eight patients
      experienced CR. The 5 year OS was 59%. The median duration of event free survival
      was 2.13 years (95% CI, 0.84-3.42). CONCLUSION: Although the results of study did
      not demonstrate the advantage of double ASCT, this is the first report to outline
      the outcome of double ASCT for Korean MM patients.

PMID- 16295785
TI  - A case of uterine cervical cancer presenting with granulocytosis.
AB  - Granulocytosis occurs in 40% of patients with lung and gastrointestinal cancers,
      20% of patients with breast cancer, 30% of patients with brain tumor and ovarian
      cancer and 10% of patients with renal cell carcinoma. Granulocytosis occurs
      because of production of G-CSF, GM-CSF and IL-6. Uterine cervical carcinoma with
      granulocytosis as a paraneoplastic syndrome, however, has been rarely reported.
      We recently witnessed a case of invasive squamous cell carcinoma of the uterine
      cervix with granulocytosis. Leukocytosis developed up to 69,000/microL, and then
      normalized after chemo-radiotherapy. There was no evidence of infection, tumor
      necrosis, glucocorticoid administration, or myeloproliferative disease by
      examination of a bone marrow aspirate when granulocytosis appeared. This
      phenomenon was probably associated with the secretion of hematopoietic growth
      factors such as G-CSF, GM-CSF and IL-6 by the tumor. We suggest that, like some
      other solid tumors, cervical cancer can present with granulocytosis as a
      paraneoplastic syndrome.

PMID- 16295786
TI  - Congenital double-orifice mitral valve with mitral regurgitation due to flail
      leaflet in an elderly patient.
AB  - We report here on a case of double-orifice mitral valve with mitral regurgitation
      in a 75-year-old female who had complaints of mild dyspnea. Transthoracic and
      transesophageal echocardiography showed two orifices that were supplied by their
      own chordae from a different papillary muscle. Color Doppler echocardiography
      revealed moderate to severe mitral regurgitation due to the flail posterior
      leaflet of the anterolateral orifice. Except for the persistent left superior
      vena cava, no other congenital anomaly was demonstrated. The patient became
      asymptomatic with the administration of angiotensin-converting enzyme inhibitor
      and diuretics, and she has been scheduled for long term follow-up.

PMID- 16295787
TI  - A case of avascular necrosis of the femoral head as initial presentation of
      chronic myelogenous leukemia.
AB  - Chronic myelogenous leukemia (CML) is a malignant clonal disorder of hemopoietic
      stem cells characterized by abnormal proliferation and accumulation of immature
      granulocyte. Leukostasis is one of the complications of CML and is characterized
      by partial or total occlusion of microcirculation by aggregation of leukemic
      cells and thrombi leading to respiratory, ophthalmic or neurologic symptoms. We
      experienced a rare case of avascular necrosis of the femoral head as the initial
      presentation of chronic myelogenous leukemia. A 24-year-old male patient was
      admitted to our hospital with pain in the right hip joint. The patient was
      diagnosed to be suffering from chronic myelogenous leukemia by packed marrow with
      granulocytic and megakaryocytic hyperplasia and the presence of Philadelphia
      chromosome. The right hip joint pain was attributed to avascular necrosis of the
      femoral head. And the avascular necrosis could be considered as the complication
      of chronic myelogenous leukemia due to microcirculatory obstruction of the
      femoral head. The avascular necrosis of the right femoral head was treated with
      bipolar hemiarthoplasty.

PMID- 16295788
TI  - Cutaneous metastases of pancreatic carcinoma as a first clinical manifestation.
AB  - Cutaneous metastases from pancreatic adenocarcinomas are rare lesions. The most
      common site of cutaneous metastasis is the umbilicus, and this is also known as
      the 'Sister Mary Joseph' nodule. A 68-year-old Korean male, who was previously
      healthy and asymptomatic, was seen in the dermatology department for two
      subcutaneous nodules that he had on his right forearm and his back. Histological
      examination of the right foreman nodule revealed metastatic adenocarcinoma.
      Immunohistochemical staining for cytokeratin (CK) 7 and CK 19 were positive, and
      this strongly suggested the pancreatic duct as being the primary source of the
      cancer. The abdominal computed tomography findings were compatible with
      pancreatic cancer. Clinicians should be aware that metastatic cutaneous lesions
      could be the initial presenting sign for pancreatic cancer. The
      immunohistochemical staining for CK 7 and 19 may also be helpful in the diagnosis
      of metastatic pancreatic adenocarcinoma.

PMID- 16295789
TI  - Adult onset Still's disease as a cause of acute severe mitral and aortic
      regurgitation.
AB  - Adult onset Still's disease (AOSD) is an uncommon acute systemic inflammatory
      disease of unknown origin. The clinical features include high spiking fever,
      arthralgia or arthritis, transient maculopapular rash, lymphadenopathy,
      hepatosplenomegaly, and serositis. Pericarditis is the most common cardiac
      manifestation of AOSD and occurs in approximately 30% of cases. A simultaneous
      occurrence of rapidly progressive bi-valvular regurgitation associated with AOSD
      has not been previously described. We report a case of a 55-year old woman who
      underwent mitral valve replacement and Bentall's operation due to acute severe
      mitral and aortic regurgitation associated with AOSD.

PMID- 16295792
TI  - Cardiovascular care and health: one woman's story.

PMID- 16295790
TI  - Clear cell hepatocellular carcinoma with spontaneous regression of primary and
      metastatic lesions.
AB  - The prognosis of advanced hepatocellular carcinoma (HCC) tends to be poor.
      Spontaneous regression of this lesion is extremely rare. In this report, we
      describe a case of HCC which spontaneously regressed along with a metastatic
      lesion of the chest wall. A huge HCC in the right lobe, the largest diameter of
      which was about 15 x 12 cm, developed in a 72-year-old man. He and his family
      refused further treatment. Three months after the diagnosis, metastasis to the
      chest wall was detected. We prescribed a painkiller for him in order to alleviate
      chest pain. Fourteen months after the diagnosis, the tumor size of the primary
      lesion was downsized to 3 x 4 cm in diameter. A biopsy taken from the chest wall
      proved to be clear cell HCC (CHCC). Since then, the metastatic lesion has also
      disappeared. Here, we report this unusual histologically proven CHCC with
      literature reviews.

PMID- 16295793
TI  - Women's hypertension management in Canada: golden opportunity for nursing or
      continuation of the medical practice model.

PMID- 16295794
TI  - Women's experiences of heart surgery recovery: a poetical dissemination.
AB  - In this article, I provide a review of the empirical literature on women's
      experiences of recovery from heart surgery. I suggest that recovery is gendered
      in that women's experiences interface with the spaces and places that women
      inhabit. As a result, it is important for nurses to consider care from an
      interpretive framework. Recognizing the need to tailor research dissemination to
      the subject matter at hand (peoples' experiences) and the research methodology
      most appropriate to inquire into peoples' experiences (qualitative), I employ an
      unconventional method of research dissemination in the literary form of poetry.
      The type of evidence that emerges within qualitative research demands we take a
      critical look at how we disseminate knowledge. Poetical dissemination of research
      may engage nurses on a different level of thinking and invite nurses to
      reconceptualize their practice based on the evidence.

PMID- 16295795
TI  - Gender of the care environment: influence on recovery in women with heart
      disease.
AB  - Women experience higher levels of distress than men (depression, anxiety, poor
      quality of life) after a first myocardial infarction. Sex differences in distress
      are not present in predominantly female diseases such as arthritis. This study
      explored the possibility that the predominantly male treatment environment for
      heart disease accounted for some of the sex differences in distress. METHODS: Men
      and women who had experienced a first-MI were asked to complete the Bem Sex Role
      Inventory (BSRI), a modified version of the Moos Ward Atmosphere Scale (WAS) and
      measures of illness intrusiveness, depression, anxiety and quality of life.
      Gender syntony was defined as a match between patient gender (BSRI) and the
      perceived gender of the treatment environment (WAS). RESULTS: Women experienced
      higher levels of distress than men and were more likely to experience discordance
      between their gender and the perceived gender of the care environment (73% of
      women versus 32% of men). The presence of gender dystony (a mismatch between
      gender and treatment environment) was related to higher levels of illness
      intrusiveness and overall distress. CONCLUSIONS: Modification of the heart
      disease treatment environment so that it better meets the needs of women may
      reduce sex differences in distress.

PMID- 16295796
TI  - Women's cardiac rehabilitation: improving access using principles of women's
      health.
AB  - There is growing awareness among health care providers, government and community
      organizations that sex and gender are relevant to issues of health.
      Cardiovascular disease (CVD) is one area that has been in the spotlight with
      respect to sex and gender differences. The myth that CVD is a 'man's disease' has
      been thoroughly debunked and it is now acknowledged that CVD is the number one
      killer of women in Canada. Despite this, cardiac rehabilitation (CR) programs are
      largely under-utilized by women. This paper presents a case study of a CR program
      in Toronto and describes how one hospital has used their Principles of Women's
      Health to address barriers to CR for women. The Principles of Women's Health are
      described, program elements that embody these principles are reviewed and
      implications for the future of CR for women are discussed.

PMID- 16295797
TI  - Maternal cardiac autonomic function and fetal heart rate in preeclamptic compared
      to normotensive pregnancies.
AB  - BACKGROUND: Preeclampsia during pregnancy increases a woman's risk of
      cardiovascular disease in two ways. Women who develop preeclampsia are at
      increased risk for the development of hypertension and cardiovascular disease
      later in life. As well, fetal adaptations (e.g., growth restriction) may lead to
      the development of cardiovascular risk factors (e.g., obesity, increased
      cholesterol) in the offspring. Although atypical maternal cardiac autonomic
      function has been reported in preeclampsia, to date, its effects on fetal cardiac
      function have not been determined. PURPOSE: To characterize the pattern of short
      term maternal cardiac autonomic modulation and spontaneous fetal heart rate
      changes in preeclamptic compared to normotensive women and to determine the
      relationship between them. METHOD: Twenty-seven mother-fetal pairs (n = 9
      preeclamptic, n = 18 normotensive) at 32 to 40 weeks gestation were tested on one
      occasion. Maternal autonomic modulation of heart rate was measured for 20 minutes
      using electrocardiographic and beat-by-beat arterial systolic blood pressure
      recordings. Simultaneously, spontaneous fetal heart rate was obtained using a
      cardiotachograph. Women's cardiac autonomic responses to orthostatic stress were
      obtained for five minutes in a standing position. RESULTS: Comparisons of
      maternal cardiac measures in the preeclamptic versus the normotensive group
      showed that the preeclamptic group had a decreased parasympathetic nervous system
      indicator and an increased sympathetic nervous system indicator with increasing
      gestation. In response to orthostatic stress, women in both groups showed a
      similar increase in arterial systolic blood pressure and a decrease in
      parasympathetic nervous system indicator and R-R interval when standing compared
      to lying. Fetuses in the normotensive compared to the preeclamptic group had more
      spontaneous fetal heart rate accelerations; the greater the decrease in the
      parasympathetic nervous system indicator from lying to standing, the greater the
      number of fetal heart rate accelerations. CONCLUSIONS: These findings serve to
      further our understanding of the cardiovascular pathophysiology of preeclampsia
      in both the mother and the fetus. Women who develop preeclampsia during pregnancy
      show atypical autonomic nervous system modulation of heart rate that is
      associated with a decrease in spontaneous fetal heart rate accelerations in late
      gestation. Implications for cardiovascular nursing practice include the
      monitoring of maternal cardiac autonomic function during pregnancy, especially
      during standing, as well as a need for continued surveillance of maternal
      cardiovascular function following pregnancy. The negative effect on fetal heart
      rate accelerations has implications for the interpretation of standardized
      obstetrical tests of fetal well-being.

PMID- 16295798
TI  - Cardiovascular health in Canadian women: the bigger picture revisited.
AB  - Cardiovascular disease (CVD) is the leading cause of death in Canadian women.
      Recent projections suggest that the number of cardiovascular-related deaths among
      women will continue to increase for at least another decade (Heart & Stroke
      Foundation of Canada, 2003). Nurses are in pivotal roles to facilitate the
      development of strategies to promote cardiovascular health and prevent CVD in
      this population. These strategies must move beyond the current focus on the
      individual, to encompass the bigger picture of population health promotion. This
      paper revisits the current state of knowledge of the population-based
      determinants of cardiovascular health in women, incorporates a Canadian
      perspective by including relevant epidemiological data, and recommends strategies
      that extend beyond the individual to the broader community, policy, health
      services and research domains.

PMID- 16295800
TI  - Extraction of retained primary teeth in the dog.

PMID- 16295799
TI  - Participatory Action Research (PAR): a strategy for women's health research in
      the cardiovascular field.

PMID- 16295801
TI  - Surgical endodontics in dogs: a review.
AB  - Surgical endodontic therapy (apical surgery) is a treatment alternative aimed at
      removing periapical inflammatory tissue followed by apical resection and retro
      filling of the root canal. These procedures are performed through a trans-osseous
      approach. Terminology pertinent to this article include: apical (periapical)
      curettage--a surgical procedure to remove diseased tissue from the alveolar bone
      in the apical region of a pulpless tooth; apical cyst--a cyst in bone at the apex
      of a pulpless tooth. It is believed that such cysts arise after the death of the
      pulp from noxious physical, chemical, or bacterial stimulation of epithelial
      rests of Malassez; apicoectomy (apical resection) amputation of the apical
      portion of the root and removal of soft tissue in the bone; epithelial rests of
      Malassez--cords, strands, or clusters of ectodermal cells in the periodontal
      ligament (or sometimes alveolar bone) derived from remnants of Hertwigs
      epithelial root sheath. These cells frequently begin proliferating when
      inflammation occurs in the periodontal ligament and are believed to be
      responsible for the genesis of the epithelial lining of apical cysts.

PMID- 16295802
TI  - Evaluation of a barrier dental sealant in dogs.
AB  - A study was conducted in 40 healthy, randomly selected, client-owned, mixed and
      purebred dogs to assess the efficacy of a barrier dental sealant. All dogs showed
      evidence of dental plaque, calculus, or gingivitis. The dental sealant was
      applied to one side of the mouth following a professional teeth cleaning
      procedure and reapplied weekly for 8-weeks following the cleaning procedure.
      Dental parameters evaluated included plaque, calculus, gingivitis, and gingival
      bleeding indices. A statistically significant difference was detected between
      treated and untreated teeth compared with baseline values for plaque and calculus
      at weeks 4 and 8, gingivitis at week 4, and gingival bleeding time at week 8. A
      professional teeth cleaning procedure followed by a single application of the
      barrier dental sealant and weekly reapplication performed by a veterinarian or
      veterinary technician provided significant improvement in plaque and calculus
      indices during an 8-week period.

PMID- 16295803
TI  - Management of generalized gingival enlargement in a dog--case report and
      literature review.
AB  - The present report describes treatment of a dog with generalized gingival
      enlargement and serves as a review of etiology and treatment options for this
      condition. The combined use of scalpel blade, electrosurgical equipment, and a 12
      fluted bur on a high-speed handpiece with water irrigation allowed for accurate
      excision of excess gingival tissue and contouring of remaining gingiva. Surgery
      coupled with professional dental cleaning/periodontal therapy can decrease the
      recurrence of this condition. In addition, home oral hygiene is an important
      component of the treatment plan. The history of patients with gingival
      enlargement should be reviewed carefully, including drug history and previous
      medical conditions, in an attempt to elucidate a specific cause and thus allow
      for greater long-term success.

PMID- 16295804
TI  - Acrylic splint and circumferential mandibular wire for mandibular fracture repair
      in a dog.

PMID- 16295805
TI  - Normal occlusion in the dog.

PMID- 16295806
TI  - Single mucoperiosteal flap for oronasal fistula repair.

PMID- 16295807
TI  - Osteoporosis treatment in 2005.

PMID- 16295808
TI  - The challenge of nontuberculous mycobacteria in patients with cystic fibrosis.

PMID- 16295809
TI  - New face of the old foe: central nervous system tuberculosis.

PMID- 16295810
TI  - Extrahepatic manifestations of hepatitis C.

PMID- 16295811
TI  - Automatic transport ventilator versus bag valve in the EMS setting: a
      prospective, randomized trial.
AB  - PURPOSE: The primary objective of this study was to compare Emergency Medical
      Technicians-Paramedics (EMT-P) perceptions of the usefulness of an automatic
      transport ventilator (ATV) compared with bag valve (BV) ventilation for intubated
      patients. METHODS: Cardiopulmonary resuscitation or assisted ventilation patients
      were randomly assigned by day to the ATV or BV arm of the study. Questionnaires
      were completed by the EMT-Ps at the conclusion of each patient enrollment. EMT-Ps
      were asked to rate the modality used (ATV versus BV) on ease of use, time of
      setup, expedition of transport, additional tasks completed, documentation,
      overall patient care, and patient comfort. RESULTS: Twenty-eight patients were
      entered into the study, 14 in the BV arm and 14 in the ATV arm. There were
      significant differences in favor of the ATV in ability to accomplish additional
      tasks (P = 0.01), ability to document (P = 0.04), and ability to provide patient
      care (P = 0.03) CONCLUSIONS: EMT-Ps were able to accomplish more tasks, document
      more completely, and provide better patient care with the use of the ATV.

PMID- 16295812
TI  - Healthy life expectancy for selected race and gender subgroups: the case of
      Tennessee.
AB  - OBJECTIVE: To analyze healthy life expectancy (HLE) for major racial and gender
      subgroups, based on the diverse population of Tennessee and compared with the
      United States. MATERIALS AND METHODS: We use life table methodology and the HLE
      calculation model of the National Center for Health Statistics (NCHS), using two
      databases for 2001: NCHS National Vital Statistics Reports life tables and CDC
      Behavioral Risk Factor Surveillance System (BRFSS) survey. RESULTS: For
      Tennessee, although average total life expectancy (TLE) is 73.6 years at birth,
      only 61.1 years of "good" health are expected. Substantial racial and gender
      differences are found in both TLEs and HLEs with black males having the lowest
      and white females the highest. Although females have longer TLE, they spend more
      years in an unhealthy state than males. CONCLUSIONS: The findings raise new
      challenges for researchers and health policy makers for accomplishing the dual
      goals of longer life expectancy and elimination of health disparities among
      population subgroups.

PMID- 16295813
TI  - Biological age--a concept whose time has come: a preliminary study.
AB  - OBJECTIVE: Chronology poorly predicts biological age (BA) or physiologic reserve
      (PR). An objective approach to the heterogeneity of aging would greatly help
      clinical decision making in the elderly. MATERIALS AND METHODS: The first pilot
      study evaluated 130 "healthy" volunteers, ages 70 to 95 years. A summary BA/PR
      index was developed, using measures of endurance, strength, flexibility, balance,
      cognition, depression, comorbidity, and exercise. The second study applied the
      BA/PR concept to prediction of death after a first elective coronary artery
      bypass graft, using a Veterans Administration database. RESULTS: The BA/PR index
      was a better predictor of 3-year functional outcomes and death than was
      chronological age. In the coronary artery bypass graft study, the inclusion of
      BA/PR variables significantly improved prediction of 6-month and long-term death
      for Veterans Administration patients. CONCLUSIONS: The usefulness of a biological
      age (BA/PR) approach in predicting outcomes in the elderly was supported. Needed
      research should develop tools for routine "tracking" of the aging process.

PMID- 16295814
TI  - Injury risk in professional boxing.
AB  - OBJECTIVE: Although a popular endeavor, boxing has fallen under increased
      scrutiny because of its association with traumatic brain injury. However, few
      studies have investigated the overall epidemiology of boxing injuries from
      representative samples, and no study has ever documented the incidence of
      injuries in female boxers. This study is a review of professional boxing data
      from the state of Nevada from September 2001 through March 2003. MATERIALS AND
      METHODS: Medical and outcome data for all professional boxing matches occurring
      in Nevada between September 2001 and March 2003 (n = 524 matches) were analyzed
      on the basis of a pair-matched, case-control design. Cases were boxers who
      received an injury during the boxing matches. Boxers who were not injured served
      as control subjects. Both conditional and unconditional logistic regression
      models were used to assess risk factors for injury. RESULTS: The overall
      incidence rate of injury was 17.1 per 100 boxer-matches, or 3.4 per 100 boxer
      rounds. Facial laceration accounted for 51% of all injuries, followed by hand
      injury (17%), eye injury (14%), and nose injury (5%). Male boxers were
      significantly more likely than female boxers to receive injuries (3.6 versus 1.2
      per 100 boxer-rounds, P = 0.01). Male boxing matches also ended in knockouts and
      technical knockouts more often than did female matches (P < 0.001). The risk of
      injury for those who lost the matches was nearly twice the risk for the winners.
      Those who lost by knockout had double the risk of injury compared with those who
      lost by other means. Neither age nor weight was significantly associated with the
      risk of injury. CONCLUSIONS: The injury rate in professional boxing matches is
      high, particularly among male boxers. Superficial facial lacerations are the most
      common injury reported. Male boxers have a higher rate of knockout and technical
      knockouts than female boxers. Further research is necessary to determine the
      outcomes of injury, particularly the long-term neurologic outcome differences
      between sexes.

PMID- 16295815
TI  - Review of treatment modalities for postmenopausal osteoporosis.
AB  - This review summarizes and updates data presented at recent annual Southern
      Medical Association conferences on postmenopausal osteoporosis. As part of any
      osteoporosis treatment program, it is important to maintain adequate calcium and
      25-hydroxyvitamin D levels either through diet or supplementation. Among the
      available pharmacologic therapies, the bisphosphonates alendronate and
      risedronate have demonstrated the most robust fracture risk reductions
      approximately 40 to 50% reduction in vertebral fracture risk, 30 to 40% in
      nonvertebral fracture risk, and 40 to 60% in hip fracture risk. Ibandronate, a
      new bisphosphonate, has demonstrated efficacy in reducing vertebral fracture
      risk. Salmon calcitonin nasal spray and raloxifene demonstrated significant
      reductions in vertebral fracture risk in pivotal studies. Teriparatide
      significantly reduced vertebral and nonvertebral fracture risk. Drugs on the
      horizon include strontium ranelate, which has been shown to reduce vertebral and
      nonvertebral fracture risk, and zoledronic acid, an injectable bisphosphonate
      that increased bone density with once-yearly administration.

PMID- 16295816
TI  - Extrahepatic manifestations of hepatitis C.
AB  - Hepatitis C affects approximately 170 million people worldwide. Extrahepatic
      manifestations of chronic hepatitis C infection are clinically evident in nearly
      40% of patients. Much research has been done over the last decade to better
      understand their incidence, clinical presentation, mechanism of disease, and the
      role of antiviral therapy in their treatment. Of the commonly reported
      manifestations, cryoglobulinemia, membranoproliferative glomerulonephritis, and
      porphyria cutanea tarda remain the best understood manifestations. More recently,
      the association of insulin resistance and diabetes mellitus with chronic
      hepatitis C has been demonstrated. This paper serves to review the growing body
      of literature detailing the extrahepatic manifestations of chronic hepatitis C.

PMID- 16295817
TI  - Vitamin D: important for prevention of osteoporosis, cardiovascular heart
      disease, type 1 diabetes, autoimmune diseases, and some cancers.
AB  - Vitamin D is very important for overall health and wellbeing. A major source of
      vitamin D comes from exposure to sunlight. Measurement of 25-hydroxyvitamin D in
      the blood and not 1,25-dihydroxyvitamin D is used to determine vitamin D status.
      A blood level of 25-hydroxyvitamin D of at least 20 ng/mL is considered to be
      vitamin D sufficient. Vitamin D deficiency increases the risk of many common
      cancers, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular
      heart disease, and type I diabetes.

PMID- 16295818
TI  - Two unusual sequelae of tuberculous meningitis despite treatment.
AB  - We describe the case of a 22-year-old HIV-negative male who was diagnosed with
      tuberculous meningitis and subsequently went on to develop two highly unusual
      after effects of the meningitis. The first was a tuberculoma, which was
      discovered 28 days after the meningitis and occurred while the patient was taking
      a four-drug therapeutic regimen, despite adequate drug susceptibilities. The
      second was an even more unique sequela: tuberculous radiculomyelitis. This
      transpired only after the patient's glucocorticoids, which were initiated to
      treat the tuberculoma, were tapered off. These manifestations were successfully
      treated with the addition of corticosteroids to the antituberculous regimen. The
      typical clinical presentations of these diseases are reviewed and various means
      of pathogenesis proposed.

PMID- 16295819
TI  - Acute respiratory distress syndrome in a child with Kawasaki disease.
AB  - This report presents a case of classic Kawasaki disease with progression to acute
      respiratory distress syndrome. The severity of the patient's pulmonary disease
      led clinicians to suspect toxic shock syndrome. Clinicians need to be aware that
      pulmonary manifestations of Kawasaki disease can include acute respiratory
      distress syndrome.

PMID- 16295821
TI  - A case of Mycobacterium avium complex pulmonary disease in an immunocompetent
      host.
AB  - Mycobacterium avium complex is the most common of nontuberculous mycobacterium
      capable of causing disease in humans. The manifestations can vary from
      asymptomatic exposure to hypersensitivity pneumonitis to advanced fibrocavitary
      disease. We describe the case of a 37-year-old male with advanced cavitary
      disease from Mycobacterium avium complex. The patient had no previous history of
      pulmonary disease, but did have a history of snorting crushed Lortab
      (hydrocodone/acetaminophen) tablets and we postulate that possible injury to the
      lung from talc or other chemicals in the tablets may have predisposed him to
      develop Mycobacterium avium pulmonary disease.

PMID- 16295820
TI  - Concurrence of granular cell tumor and Mycobacterium tuberculosis.
AB  - Granular cell tumors (GCT) are rare, usually benign neoplasms of Schwann cell
      origin. Since discovery in 1926, fewer than 80 cases of GCT involving the lung
      have been reported. This report presents a 45-year-old male who presented with
      symptoms consistent with chronic pancreatitis associated with night sweats,
      weight loss, and a chronic productive cough. Chest radiography revealed a 3 x 4
      cm left upper lobe lung mass with an unremarkable right lung field. Bronchoscopy
      revealed mixed mucosal abnormalities in the left upper lobe and a 4-mm polypoidal
      lesion in the right lower lobe. Bronchial washings stained positive for acid-fast
      bacilli. The left upper lobe lesion biopsy showed granulomatous inflammation with
      caseous necrosis consistent with tuberculosis. The right lower lobe lesion was a
      GCT without evidence of tuberculosis. This report reviews the literature
      regarding GCT and presents this unusual case of granular cell tumor co-occurring
      with active tuberculosis.

PMID- 16295822
TI  - Paradoxical inflammatory reaction to Seprafilm: case report and review of the
      literature.
AB  - This report describes a paradoxical inflammatory reaction to Seprafilm caused by
      extensive adhesion formation early in the postoperative period. A female patient
      had development of small bowel obstruction immediately after an uneventful low
      anterior resection for rectal carcinoma with placement of Seprafilm. The
      obstruction did not improve with nonoperative therapy. At laparotomy, extensive
      adhesions necessitating bowel resection and ileostomy were noted. Pathology
      results showed a giant cell foreign body reaction to Seprafilm. A literature
      search yielded only two other instances of adverse reactions to Seprafilm. The
      information provided by this and other atypical reports suggests that further
      studies aimed at identifying the incidence and pathophysiological mechanisms for
      such paradoxical reactions are needed.

PMID- 16295823
TI  - Large gastric trichobezoar in a normal healthy woman: case report and review of
      pertinent literature.
AB  - This report presents a unique case of a gastric trichobezoar in a relatively
      healthy, young female with no history of psychological or psychiatric disorders.
      Furthermore, unlike previously reported cases, this patient had no history of
      gastric surgery. The mode of presentation and the difficulties in diagnosis are
      discussed. The different modalities of treatment, both surgical and nonsurgical,
      are evaluated and discussed. The diagnosis of a trichobezoar in a healthy patient
      requires a high index of suspicion, as it can present with nonspecific
      symptomatology. It should be included in the differential diagnosis of
      nonspecific abdominal pain.

PMID- 16295824
TI  - Multifocal primary breast lymphoma.
AB  - Primary breast lymphoma (PBL) is a rare condition, accounting for only 0.04 to
      0.5% of breast malignancies and less than 2% of extranodal lymphomas. Clinical
      presentation and imaging may suggest a benign condition. Reports of treatment
      vary widely. Surgical therapy has been reported to include only biopsy or extend
      to partial mastectomy, total mastectomy, or even radical mastectomy. Chemotherapy
      with various agents is often used. Radiotherapy has been used in the adjuvant
      setting or as primary local therapy. Immunotherapy and radioimmunotherapy have
      shown some promise in other lymphomas and may be useful here as well. There is no
      standard or consensus of treatment for PBL. This report describes a case of
      multifocal PBL in a 45-year-old female and discusses the physical findings,
      diagnosis, and treatment options for this condition.

PMID- 16295825
TI  - Eosinophilic enteritis with systemic lupus erythematosus.
AB  - Gastrointestinal manifestations are common in systemic lupus erythematosus (SLE).
      Eosinophilic enteritis is a rare disorder of uncertain cause that was recently
      reported for the first time in association with SLE. This report presents a
      second case of eosinophilic enteritis in a 47-year-old female patient with SLE.
      The patient presented with recurrent episodes of abdominal pain, nausea,
      vomiting, and diarrhea. Complete blood counts on occasion showed elevated
      eosinophil counts. The patient underwent a comprehensive workup over several
      weeks, culminating in a small bowel biopsy that showed eosinophil infiltration in
      the muscularis propria, establishing the diagnosis. The patient was treated with
      a prolonged taper of prednisone with successful resolution of symptoms.

PMID- 16295826
TI  - Radical surgical treatment for Marjolin ulcer occurring after chronic
      osteomyelitis.

PMID- 16295827
TI  - Greens could be bad for you: a study of the inappropriate use of theater greens.

PMID- 16295828
TI  - A large splenic cyst: "incindentalocyst".

PMID- 16295829
TI  - Diagnostic challenge of sphincter of oddi dysfunction in postcholecystectomy pain
      syndromes.

PMID- 16295830
TI  - The patient's page. Bone health facts.

PMID- 16295831
TI  - DBPs not associated with miscarriage.

PMID- 16295832
TI  - Are industry's secret "inerts" an unrecognized environmental danger?

PMID- 16295833
TI  - More than obvious: better methods for interpreting nondetect data.

PMID- 16295834
TI  - Acidification of soil solution in a chestnut forest stand in southern
      Switzerland: are there signs of recovery?
AB  - In a previous study, a rapid acidification of soil solution was observed between
      1987 and 1997 in a cryptopodzolic soil in southern Switzerland despite a
      reduction in acidic deposition. The molar ratio of base nutrient cations to
      aluminum (BC/Al) in the soil solution was used to assess acidification. The
      monitoring of the soil solution chemistry was continued at the same site between
      1998 and 2003 to find out how long the delay in reaction to reduced deposition
      would last and whether the BC/Al ratios would recover. The reevaluation of all
      data collected during the 16-year observation period showed no clear improvement
      in the BC/Al ratios, except below the litter layer where the ratios greatly
      increased after 1998. Initial signs of recovery were also detected in the mineral
      horizons, the ratios stabilizing in the second part of the observation period.
      Sulfate concentrations decreased significantly below the litter mat in response
      to decreased S deposition. BC concentrations markedly declined below the litter
      layer and in the mineral horizons, which was attributed to the depletion of the
      BC exchangeable pool as a result of continued acidic deposition.

PMID- 16295835
TI  - Fine (PM2.5) and coarse (PM2.5-10) particulate matter on a heavily trafficked
      London highway: sources and processes.
AB  - A large dataset for PM2.5 and PMcoarse (PM2.5-10) concentrations monitored near a
      busy London highway (Marylebone Road) has been analyzed to define the factors
      that lead to high concentrations. The following have been highlighted as major
      influencing parameters: wind speed, prevailing wind direction (because of its
      role on the microscale dispersion within the street), the daily cycle of the
      atmospheric boundary layer (stable during the night/ convective and mixed during
      the day), and traffic density. The mainly diesel heavy-duty vehicles are the main
      source of fine particulate matter at Marylebone Road. In particular, lorries
      (trucks) dominate PM10 exhaust emissions which are mainly in the fine (<2.5
      microm) size range. A strong correlation with PMcoarse suggests that the heavy
      duty traffic is largely responsible for this component also. Substantial local
      increments in PM2.5 and PMcoarse due to traffic have been estimated and a large
      part of the increment in PMcoarse concentrations is inferred to arise from
      resuspended road dust emissions since the contribution of abrasion processes
      estimated from emission factors is modest. Despite the strong influence of
      traffic on PM concentrations measured at Marylebone Road the analysis of factors
      leading to the highest 5% of hourly concentrations of PM10 at Marylebone Road
      reveals that almost half of these events were due to building works. The other
      events occurred when all or most of the key factors occurred simultaneously
      (heavy traffic, poor dispersion, etc.). Some episodes of high PM2.5
      concentrations were associated with long-range transport in which the regional
      PM2.5 constituted most of the local concentrations.

PMID- 16295836
TI  - Response of the nitrogen isotopic composition of tree-rings following tree
      clearing and land-use change.
AB  - Clear-cutting of forests affects the nitrogen cycle and the nitrogen isotopic
      composition of bioavailable ammonium and nitrate in the soil. Here, we have used
      nitrogen isotopic variations of tree-rings in red oak (Quercus rubra) and white
      oak (Quercus alba) as indicators of changes in the nitrogen cycle on a local
      scale. The delta15N values of late-wood from trees at two remnant forest stands
      in Ontario, Canada, that underwent large-scale tree-clearing and permanent land
      use change at different times were measured. Trees from the perimeter of each
      stand record a marked 1.5-2.5 per thousand increase in the delta15N values of
      their tree-rings relative to the values in trees from the center of the stand,
      with the shift synchronous with the tree-clearing and land-use change. This shift
      was most likely due to increased rates of nitrification and nitrate leaching in
      the soil as a result of tree-clearing combined with permanent changes in
      hydrology and probable fertilizer use accompanying the change in land-use.
      Nitrogen concentration in tree-rings was not affected bytree-clearing and the
      associated change in land-use. These results indicate that changes in nitrogen
      cycling in forest ecosystems, whether due to climate change, land-use change, or
      other environmental changes (increased O3, other atmospheric pollutants, insects,
      etc.), can be faithfully monitored with nitrogen isotopic compositions of tree
      rings and that dendrogeochemical analysis can be incorporated into studies of the
      effects of long-term anthropogenic effects on forest ecosystems.

PMID- 16295837
TI  - Tetra- and tribromophenoxyanisoles in marine samples from Oceania.
AB  - Some methoxylated polybrominated diphenyl ethers (MeO-BDEs) are known halogenated
      natural products (HNPs) and are frequently detected in higher organisms of the
      marine environment. In this study we demonstrate that a prominent MeO-BDE,
      previously detected in marine mammals from Australia, is identical to 3,5-dibromo
      2-(2',4'dibromo)phenoxyanisole (BC-3, 6-MeO-BDE 47). Up to 1.9 mg/ kg of 6-MeO
      BDE 47 was present in cetaceans from Australia, 0.2-0.3 mg/kg in two crocodile
      eggs from Australia, but concentrations of 1 or 2 orders of magnitude lower were
      found in shark liver oil from NewZealand and in marine mammals from Africa and
      the Antarctic. Concentrations of 6-MeO-BDE 47 in samples from Australia were in
      the same range as anthropogenic pollutants such as PCB 153 and p,p'-DDE. Along
      with 6-MeO-BDE 47 and the known HNP 4,6-dibromo-2-(2',4'-dibromo)phenoxyanisole
      (BC-2, 2'-MeO-BDE 68), several tribromophenoxyanisoles (MeO-triBDE) were present
      in tissue of Australian cetaceans. To determine their structure, abiotic
      debromination experiments were performed using 6-MeO-BDE 47 and 2'-MeO-BDE 68 and
      superreduced dicyanocobalamine. These experiments resulted in formation of eight
      MeO-triBDEs, all of which were detected in the cetacean samples. Five of these
      eight MeO-triBDEs could be identified based on two standard compounds as well as
      gas chromatographic and mass spectrometric features. It was also shown that the
      first eluting isomer (compound 1), 6-MeO-BDE 17 (compound 2), and 2-MeO-BDE 39
      (compound 5) were the most prominent MeO-triBDEs in the Australian cetacean
      samples. The concentrations of the MeO-triBDEs in two cetacean samples were 0.20
      and 0.36 mg/kg, respectively. Although the reductive debromination with
      dicyanocobalamine resulted in a different congener pattern than was found in the
      marine mammals, it could not be excluded that the tribromo

PMID- 16295838
TI  - Nitrous oxide emissions from a municipal landfill.
AB  - The first measurements of nitrous oxide (N20) emissions from a landfill by the
      eddy covariance method are reported. These measurements were compared to
      enclosure emission measurements conducted at the same site. The average emissions
      from the municipal landfill of the Helsinki Metropolitan Area were 2.7 mg N m(-2)
      h(-1) and 6.0 mg N m(-2) h(-1) measured bythe eddy covariance and the enclosure
      methods, respectively. The N20 emissions from the landfill are about 1 order of
      magnitude higher than the highest emissions reported from Northern European
      agricultural soils, and 2 orders of magnitude higher than the highest emissions
      reported from boreal forest soils. Due to the small area of landfills as compared
      to other land-use classes, the total N20 emissions from landfills are estimated
      to be of minor importance for the total emissions from Finland. Expressed as a
      greenhouse warming potential (GWP100), the N2O emissions make up about 3% of the
      total GWP100 emission of the landfill. The emissions measured by the two systems
      were generally of similar magnitude, with enclosure measurements showing a high
      small-scale spatial variation.

PMID- 16295839
TI  - Brominated flame retardants in the atmosphere of the East-Central United States.
AB  - Air samples were collected at five sites (urban, semiurban, agricultural, and
      remote) from Lake Michigan through the U. S. Midwest to the Gulf of Mexico every
      12 days during 2002-2003 using high-volume samplers so that we could study the
      spatial trends of brominated flame retardants (polybrominated diphenyl ethers
      (PBDEs), hexabromocyclododecanes (HBCDs), and 1,2-bis(2,4,6-tribromophenoxy)
      ethane (TBE)). The mean sigmaPBDE atmospheric concentration was 100 +/- 35 pg/m3
      at the Chicago site, which was 3-6 times higher than that at the other sites. The
      sigmaPBDE atmospheric concentrations at the Chicago site were significantly
      higher than previous measurements made in 1997-1999. Unlike these former
      measurements, BDE-209 is now relatively abundant. Lower BDEs (tri- through hex
      BDEs) were detected in both the particle and the gas phases, and the partitioning
      of these compounds between phases was highly dependent on atmospheric
      temperature. Higher BDEs (hepta- through deca-BDEs) were mostly detected in the
      particle phase. On the basis of the congener distributions in the samples, the
      concentrations were divided into three groups: penta-BDEs, octa-BDEs, and deca
      BDEs. Penta-BDEs were the most concentrated at the Chicago site and the least
      concentrated at the Louisiana site; octa-BDE concentrations were low at all of
      the sites; deca-BDEs were the most concentrated at the Chicago site and notably
      high atthe Arkansas site. High concentrations of deca-BDEs, HBCDs, and TBE at the
      Arkansas site suggest that manufacturing areas in southern Arkansas could be the
      source regions. Backward trajectories for air masses with high concentrations of
      deca-BDEs coming to the Arkansas site suggestthat deca-BDEs bound to particles
      can move long distances from source regions to nonsource regions.

PMID- 16295840
TI  - Polybrominated diphenyl ethers in airborne particulates collected during a
      research expedition from the Bohai Sea to the Arctic.
AB  - In July to September 2003, particulates in the oceanic atmosphere from the Bohai
      Sea to the high Arctic (37 degrees N to 80 degrees N) were collected aboard a
      research expedition icebreaker, Xuelong (Snow Dragon), under the 2003 Chinese
      Arctic Research Expedition Program (CHINARE 2003). These samples were analyzed to
      elucidate the atmospheric distributions of polybrominated diphenyl ethers (PBDEs)
      in the North Pacific Ocean and adjacent Arctic region. The levels of 11 PBDE
      congeners (BDE-28, -47, -66, -100, -99, -85, -154, -153, -138, -183, and -209;
      the sum was defined as sigma11PBDE) in the oceanic atmosphere of Far East Asia
      (34-48 degrees N/122-148 degrees E) ranged from 2.25 to 198.9 pg/m3 with a mean
      of 58.3 pg/m3. BDE-47, -99, -100, and -209 were the dominant congeners in all the
      samples, suggesting that the widely used commercial penta- and deca-BDE products
      were the original sources. The PBDE levels exhibited a decreasing trend from the
      mid- to high-latitudinal regions of the North Pacific Ocean, probably resulting
      from dilution, deposition, and decomposition of PBDEs during long-range transport
      of air masses. On the other hand, no apparent geographical pattern of PBDE
      distribution was observed within the Arctic, attributable to unstable air
      circulation and strong air mixing. Correlations among the PBDE congeners
      suggested that air masses collected from the North Pacific Ocean were relatively
      fresh, whereas those from the Arctic were aged as a result of photodecompoisiton.
      The higher average level (17.3 pg/m3) of PBDE congeners in the Arctic than those
      in the adjacent North Pacific Ocean (12.8 pg/m3) or other remote areas reported
      in the literature was attributed to the impact of the North American continent
      and temperature effects, which was consistent with the hypotheses of global
      fractionation.

PMID- 16295841
TI  - Simulated inhalation levels of fragrance materials in a surrogate air freshener
      formulation.
AB  - This study measured postapplication exposure levels of fragrance materials in a
      surrogate air freshener formulation in an environmentally-controlled exposure
      room (ECER). A five-s spray was released to simulate normal consumer use
      conditions. Time-course airborne fragrance material levels were sampled with
      Tenax tubes, and aerosol size distributions were monitored with a TSI 3320
      aerodynamic particle sizer. Triplicate experiments were performed for each of the
      control/test substances. The control substance (unfragranced formulation)
      experiments indicated that the airborne fragrance materials were not detected,
      suggesting that the base propellant formulation did not interfere with the
      sampling procedure or analytical results. The test substance experiments found
      that the higher the volatility of the fragrance material, the higherthe airborne
      fragrance concentration within the ECER. In the adult breathing zone height, the
      maximum concentrations of the nine fragrance materials ranged from 108 to 347
      microg/m3 during the first minute postapplication. In the child breathing zone
      height, the maximum fragrance material concentrations ranged from 125 to 362
      microg/m3 during 2-6 min postapplication. Particle size distributions indicated
      that approximately 60-70% of the generated aerosols were less than 1 microm
      aerodynamic diameter. Initial peak particle mass concentrations (<5 microm) were
      800-1000 microg/m3 during the first minute postapplication. Following initial
      peak concentrations, there was approximately 10-15 min of fluctuation, and then
      particle levels decayed gradually and exponentiallyto near background levels.
      Exposure to the test formulation would originate from two components: particle
      bound and vapor-phase fragrance materials. Particle-bound fragrance exposure
      accounted for approximately 47% and 72% of the total exposures during the first
      minute postapplication period in the adult and child breathing zone heights,
      respectively.

PMID- 16295842
TI  - Effects of wind and air trajectory directions on atmospheric concentrations of
      persistent organic pollutants near the Great Lakes.
AB  - Three different regression models involving air temperature, time, and either
      wind direction or parametric or nonparametric air trajectory direction were used
      with concentrations of four representative persistent organic pollutants to
      quantitate the atmospheric transport of these compounds to the Great Lakes. The
      local wind and parametric trajectory models predicted an optimal source direction
      for each compound, whereas the nonparametric trajectory model was based on a
      hypothesized source region. All three regressions were used to calculate the
      factor by which the partial pressures of each compound measured at five sampling
      sites increased when the air came from a particular source direction. Dieldrin,
      chlordane, polychlorinated biphenyl, and polycyclic aromatic hydrocarbon partial
      pressures were used with each of these regressions, and the correlation
      coefficients (r2) were evaluated for each model, for each compound, and for each
      regression term. In general, with the exception of polycyclic aromatic
      hydrocarbons at some sites, the explanatory powers of the regressions were not
      improved by the inclusion of any of these directional terms.

PMID- 16295843
TI  - Effects of soluble ferri-hydroxide complexes on microbial neutralization of acid
      mine drainage.
AB  - Heterotrophic respiration of ferric iron by Acidiphilium cryptum was investigated
      in anoxic microcosms with initial media pH values from 1.5 to 3.5. No organic
      carbon consumption or iron reduction was observed with an initial pH of 1.5,
      indicating that A. cryptum may not be capable of iron respiration at this pH.
      Significant iron reduction was observed at pH 2.5 and 3.5, with different
      effects. When the initial pH was 3.5, pH increased to 4.7-5.5 over 60 days of
      incubation with simultaneous production of 0.4 g L(-1) Fe2+. However, at an
      initial pH of 2.5, no significant change in pH was observed during iron
      respiration, although the accumulation of soluble ferrous iron was significantly
      higher, averaging 1.1 g L(-1) Fe2+. The speciation of the ferric iron electron
      acceptor may explain these results. At pH values of 3.5 and higher, precipitated
      ferric hydroxide Fe- (OH)3 would have been the primary source of ferric iron,
      with reduction resulting in net production of OH- ions and the significant
      increases in media pH observed. However at pH 2.5, soluble complexes, FeOH2+ and
      Fe(OH)2+, may have been the more prevalent electron acceptors, and the alkalinity
      generated by reduction of complexed iron was low. The existence of charged ferri
      hydroxide complexes at pH 2.5 was verified by voltammetry. Results suggest that
      initiation of bacterial iron reduction may result in neutralization of acid mine
      drainage. However, this effect is extremely sensitive to iron speciation within a
      relatively small and critical pH range.

PMID- 16295844
TI  - Chromate reduction and retention processes within arid subsurface environments.
AB  - Chromate is a widespread contaminantthat has deleterious impacts on human health,
      the mobility and toxicity of which are diminished by reduction to Cr(III). While
      biological and chemical reduction reactions of Cr(VI) are well resolved,
      reduction within natural sediments, particularly of arid environments, remains
      poorly described. Here, we examine chromate reduction within arid sediments from
      the Hanford, WA site, where Fe(III) (hydr)oxide and carbonate coatings limit
      mineral reactivity. Chromium(VI) reduction by Hanford sediments is negligible
      unless pretreated with acid; acidic pretreatment of packed mineral beds having a
      Cr(VI) feed solution results in Cr(III) associating with the minerals antigorite
      and lizardite in addition to magnetite and Fe(II)-bearing clay minerals. Highly
      alkaline conditions (pH > 14), representative of conditions near high-level
      nuclearwaste tanks, result in Fe(II) dissolution and concurrent Cr(VI) reduction.
      Additionally, Cr(III) and Cr(VI) are found associated with portlandite,
      suggesting a secondary mechanism for chromium retention at high pH. Thus, mineral
      reactivity is limited within this arid environment and appreciable reduction of
      Cr(VI) is restricted to highly alkaline conditions resulting near leaking
      radioactive waste disposal tanks.

PMID- 16295845
TI  - Variations of the particulate carbon distribution from a nonroad diesel
      generator.
AB  - The emissions of diesel particulate matter (DPM) from diesel engines are causing
      increasing health concerns due to their suspected carcinogenicity, especially the
      carbonaceous fractions. The total DPM emissions and the organic and elemental
      carbon (OC and EC) distributions of the DPM depend on many operating factors,
      such as load, engine design parameters, fuel sulfur content, fuel usage rate, and
      sampling conditions. Results of previous studies on the OC/EC variations with
      load for heavy-duty vehicles have been reported, but information is scarce for
      nonroad diesel generators. There is a clear need to better characterize nonroad
      DPM emissions, as studies have indicated that DPM emissions from nonroad diesel
      engines are significantly higher than those from on-road sources. The objective
      of the study is to provide a detailed account of the OC/EC distributions for a
      nonroad diesel generator operated with high and low sulfur fuels under different
      load conditions. DPM emissions were collected using an EPA Method 5
      (Determination of Particulate Matter Emissions from Stationary Sources) sampling
      train. The OC and EC concentrations were quantified by NIOSH Method 5040. DPM
      concentrations and the relative contributions of OC, EC, and noncarbonaceous
      materials vary significantly with engine load, fuel sulfur content, and sample
      collection temperature. The fractions of EC over DPM increase with increasing
      load from 21% at OkW to 84% at 75 kW for the low sulfur fuel, while those of OC
      decrease from 62% to 9%. This is consistent with other studies, and the same
      trends exist regardless of the sulfur content and DPM collection temperature. The
      fractions of organic compounds range from 77% to 19% for the high sulfur fuel.
      Noncarbonaceous materials are from 27% to 18% in fraction from high sulfur DPM as
      opposed to the 17% to 7% in the low sulfur diesel emissions. At lower collection
      temperatures, more OC and noncarbonaceous materials are observed.

PMID- 16295846
TI  - Spectral sensitivity of Bacillus subtilis spores and MS2 coliphage for validation
      testing of ultraviolet reactors for water disinfection.
AB  - The microbicidal UV fluence under polychromatic radiation from UV lamps is
      typically measured using the DNA absorbance spectrum as a weighting factor for
      the relative wavelength effectiveness. However, this DNA-based weighting does not
      necessarily match the spectral sensitivity of the microorganism being tested.
      Bacillus subtilis spores are often used for UV reactor validation in Europe,
      while MS2 coliphage is typically used for validation testing in the United
      States. These organisms were exposed to quasi-monochromatic UV irradiation across
      the microbicidal spectrum at wavelengths of 214, 230, 240, 254, 265, 280, and 293
      nm. MS2 was three times more sensitive to wavelengths near 214 nm compared to the
      254 nm output of low-pressure lamps, while B. subtilis spores were most sensitive
      to wavelengths around 265 nm. Use of these action spectra, compared to the DNA
      based weighting, resulted in differences in the calculated polychromatic UV
      fluence. Consequently, the action spectrum, which is specific for each
      microorganism, has implications on the uncertainty of UV fluence determination
      during validation of reactors with polychromatic UV lamps.

PMID- 16295847
TI  - Retention and transport of amphiphilic colloids under unsaturated flow
      conditions: effect of particle size and surface property.
AB  - The purpose of this study was to examine the mechanisms responsible for
      deposition and transport of amphiphilic colloids with a wide range of particle
      sizes (20-420 nm) through porous media. A series of saturated and unsaturated
      column experiments were conducted using amphiphilic latex microspheres and a
      hydrophilic silica colloid. We found that the amphiphilic latex particles were
      retained to a greater extentthan the hydrophilic silica colloid in unsaturated
      media. This was attributed to colloidal attachment atthe air-water interface due
      mainly to hydrophobic interactions. We also found that dependence of colloid
      retention on particle size was nonlinear. There existed a fraction of colloids
      with greater mobility than other fractions, which we referred to as the most
      mobile colloids. As particle size increased from 20 to 420 nm, colloid deposition
      rate first decreased to reach a minimum value at --100 nm then increased,
      indicating that different retention mechanisms were involved. We showed that
      conducting saturated transport experiments and analysis using filtration theory
      may be an effective approach for determining the most mobile colloid size(s) in
      porous media, perhaps even for unsaturated flow conditions. This study highlights
      the importance of including size effect and surface properties when predicting
      concentrations and fluxes of amphiphilic colloids or colloid-bound amphiphilic
      and hydrophobic contaminants in the subsurface environment.

PMID- 16295848
TI  - Transport of MS2 phage, Escherichia coli, Clostridium perfringens,
      Cryptosporidium parvum, and Giardia intestinalis in a gravel and a sandy soil.
AB  - To define protection zones around groundwater abstraction wells and safe setback
      distances for artificial recharge systems in watertreatment, quantitative
      information is needed about the removal of microorganisms during soil passage.
      Column experiments were conducted using natural soil and water from an
      infiltration site with fine sandy soil and a river bank infiltration site with
      gravel soil. The removal of phages, bacteria, bacterial spores, and protozoan
      (oo)-cysts was determined at two velocities and compared with field data from the
      same sites. The microbial elimination rate (MER) in both soils was generally >2
      log, but MER in the gravel soil was higher than that in the fine sandy soil. This
      was attributed to enhanced attachment, related to higher metal-hydroxides
      content. From the high sticking efficiencies (>1) and the low influence of flow
      rate on MER it was deduced that straining played a significant role in the
      removal of Escherichia coli and Cryptosporidium parvum oocysts in the gravel
      soil. Lower removal of oocysts than the 4-5 times smaller E. coli and spores in
      the fine sand indicates that the contribution of straining is variable and needs
      further attention in transport models. Thus, simple extrapolation of grain size
      and particle size to the extent of microbial transport underground is
      inappropriate. Finally, the low MER of indigenous E. coli and Clostridium
      perfringens observed in the soil columns as well as under field conditions and
      the second breakthrough peak found for Cryptosporidium and spores in the fine
      sandy soil upon a change in the feedwater pH indicate a significant role of
      detachment and retardation to microbial transport and the difficulty of
      extrapolation of quantitative column test results to field conditions.

PMID- 16295849
TI  - Role of organic acids in promoting colloidal transport of mercury from mine
      tailings.
AB  - A number of factors affect the transport of dissolved and particulate mercury
      (Hg) from inoperative Hg mines, including the presence of organic acids in the
      rooting zone of vegetated mine waste. We examined the role of the two most common
      organic acids in soils (oxalic and citric acid) on Hg transport from such waste
      by pumping a mixed organic acid solution (pH 5.7) at 1 mL/min through Hg mine
      tailings columns. For the two total organic acid concentrations investigated (20
      microM and 1 mM), particle-associated Hg was mobilized, with the onset of
      particulate Hg transport occurring later for the lower organic acid
      concentration. Chemical analyses of column effluent indicate that 98 wt % of Hg
      mobilized from the column was particulate. Hg speciation was determined using
      extended X-ray absorption fine structure spectroscopy and transmission electron
      microscopy, showing that HgS minerals are dominant in the mobilized particles. Hg
      adsorbed to colloids is another likely mode of transport due to the abundance of
      Fe-(oxyhydr)oxides, Fe-sulfides, alunite, and jarosite in the tailings to which
      Hg(II) adsorbs. Organic acids produced by plants are likely to enhance the
      transport of colloid-associated Hg from vegetated Hg mine tailings by dissolving
      cements to enable colloid release.

PMID- 16295850
TI  - Effects of dissolved carbonate on arsenic adsorption and mobility.
AB  - The effects of high aqueous carbonate concentrations on arsenic mobility and
      transport in the subsurface were studied in synthetic iron oxide-coated sand
      column experiments. Elevated aqueous carbonate concentrations in groundwater have
      been studied and linked, by some authors, to increased aqueous As concentrations
      in natural waters. This study found that increasing carbonate concentrations had
      relatively little effect on As(V) adsorption to the iron oxide-coated sand
      surface at pH 7. The adsorption of As(V) decreased marginally when the CO2(g)
      partial pressure increased from 10(-3.5) to 10(-1.8) atm, despite a 50-fold
      increase in total dissolved carbonate (0.072 to 3.58 mM). Increasing the CO2(g)
      partial pressure to 10(-10) atm resulted in only a slight decrease in As(V)
      adsorption and increase in mobility, despite a >300-fold increase in total
      dissolved carbonate (to 22.7 mM). When compared to phosphate, a known competitive
      anion, carbonate mobilized less adsorbed As(V) than was mobilized by phosphate,
      even when present in much higher concentrations than phosphate. This was also
      true for an experiment with lower pore water velocity and an experiment where
      As(II) was introduced instead of As(V). Our experiments conclude that while
      carbonate anions do compete with As for adsorption to iron oxide-coated sand, the
      competitive effect is relatively small with regard to the total concentration of
      adsorbed As and the potential competitive effects of phosphate.

PMID- 16295852
TI  - Extremely slowly desorbing polycyclic aromatic hydrocarbons from soot and soot
      like materials: evidence by supercritical fluid extraction.
AB  - Combustion-derived PAHs are strongly sorbed to their particulate carrier (i.e.,
      soot, charcoal), and therefore, very slow desorption kinetics of the chemicals
      might be anticipated. Measurements are however lacking, because conventional
      methods (Tenax, XAD, gas-purging) fail to accurately determine desorption
      kinetics due to practical problems. In this study, we used a mild supercritical
      fluid extraction (SFE) method, which mimics desorption into water and circumvents
      these problems, to quantify desorption kinetics of 13 native PAHs from pure
      charcoal, coal, and four types of soot. The results show that generally only very
      small PAH fractions are released. Desorption behavior was, however, not related
      to common sorbent/sorbate characteristics. Two-site model-derived "fast desorbing
      fractions" were <0.01 in the majority of cases, and for the dominant "slow
      sites", the calculated rate constants for desorption into water measured from 10(
      7) to 10(-5) h(-1). These data suggest that desorption of coal and combustion
      derived PAHs can be even slower than the "very slow" desorption observed in
      sediments. Estimated time scales required for removal of pyrogenic PAHs from
      these extremely slow sites into water amount to several millennia. Our results
      imply reduced chemical risks for soot and soot-like materials, casting doubts on
      current risk assessment procedures and environmental quality standards of
      pyrogenic PAHs.

PMID- 16295851
TI  - Measured mass transfer coefficients in porous media using specific interfacial
      area.
AB  - Bulk and intrinsic mass transfer processes across interfaces between nonaqueous
      phase liquids (NAPLs) and water were studied in water-saturated columns. Columns
      packed with different grain sizes of sand were used to create various NAPL-water
      interfacial areas along with different NAPL saturations. The intrinsic mass
      transfer coefficients were estimated from the bulk mass transfer coefficients,
      and the specific interfacial areas were measured using tracer studies. The bulk
      mass transfer coefficients increased with increasing NAPL-water specific
      interfacial area as well as NAPL saturation and pore velocity and with decreasing
      grain sizes. Moreover, the bulk mass transfer coefficients were correlated with
      NAPL-water specific interfacial area rather than NAPL saturation and were more
      sensitive at high NAPL-water interfacial areas than at low interfacial areas. In
      contrast, the intrinsic mass transfer coefficients were nearly independent of
      specific interfacial area and NAPL saturation but dependent on pore velocity.
      Reduction of NAPL saturation by dissolution caused a linear decrease in the bulk
      mass transfer coefficients.

PMID- 16295853
TI  - Occurrence of a nitro metabolite of a defined nonylphenol isomer in soil/sewage
      sludge mixtures.
AB  - Uniformly [14C]-ring-labeled 4-(3,5-dimethyl-3-heptyl)phenol (353-nonylphenol) is
      a highly relevant isomer of the technical nonylphenol mixture. We studied the
      sorption, desorption, and degradation of the synthesized isomer in an
      agricultural sandy loam at various soil/sewage sludge ratios. Sorption of 353
      nonylphenol was high and differed with the amount of suspended soil in water. log
      Koc values, which are used to assess the risk of nonylphenol, ranged from 3.80 to
      5.75. Desorption was slow and low and resulted in constant concentrations of
      about 15 ng/L353-nonylphenol in water after several desorption steps. In
      degradation studies up to 6% of the applied 353-nonylphenol in soil was
      volatilized; we consider this an important source of nonylphenol in the
      environment. With increasing amounts of sewage sludge in the soil/sewage sludge
      mixtures, 353-nonylphenol was stabilized, probably because of the lack of oxygen
      in sludge aggregates even under oxic conditions in flow-through systems.
      Unexpectedly, a less-polar metabolite was detected in amounts up to 40% of the
      applied nonylphenol after 135 days of incubation. This novel metabolite was
      identified as 4-(3,5-dimethyl-3-heptyl)-2-nitrophenol. This product formation
      might indicate the existence of novel metabolic pathways of nonylphenol in the
      environment.

PMID- 16295854
TI  - Proton buffering and metal leaching in sandy soils.
AB  - Recent developments in acidification research focused on the leaching of metals
      from contaminated soil. In this paper the buffering of sandy soils upon
      acidification is studied in relation to the release of major (Al, Ca, Mg) and
      trace metals (Cu, Cd, Ni, Zn) from the soil reactive surface. The buffering
      process and the (de)sorption of metals are described with a mechanistic
      multisurface model, expressing the sorption onto different soil surfaces (organic
      matter, clay, Fe (hydr)oxides). The pH of sandy soil samples is predicted upon
      proton addition in combination with the behavior of major and trace metals.
      Acidification of contaminated sandy soil samples, with different pH levels and
      metal contents, is performed in a flow-through reactor by flushing the samples
      with acid solution. Acidification has taken place in successive steps of proton
      addition and followed by sampling. Prediction of pH upon acidification with a
      multisurface model gives satisfying results for all samples studied. The pH is
      modeled reasonably well between pH 6 and 4. Below pH 4 the predicted pH values
      are slightly too low, probably due to the buffering by Al-containing minerals
      (e.g., Al hydroxide), which are not included in the model. Desorption of major
      and trace metals upon pH decrease is, in general, predicted well, within a factor
      of 1-5 on a linear scale. Overall prediction of proton buffering in combination
      with desorption of metals in sandy soil samples, over a wide pH range and metal
      content, is done quite well for the studied metals with the multisurface model.

PMID- 16295855
TI  - Inactivation of Ascaris suum eggs by ammonia.
AB  - Uncharged ammonia is known to cause inactivation of a number of wastewater
      pathogens, but its effect on Ascaris eggs has never been isolated or quantified.
      The objectives of this research were to determine the conditions under which
      ammonia inactivates eggs of the swine Ascaris species, Ascaris suum, and to
      quantify the impact of ammonia on the U.S. EPA's requirements for alkaline
      treatment to produce Class A sludge. Eggs were incubated in controlled,
      laboratory solutions such that the effects of ammonia concentration and
      speciation, pH, and temperature could be separated. With a 24-h incubation, the
      inactivation at all pH levels (range 7-11) was not statistically different in the
      absence of ammonia. The presence of ammonia (0-1000 ppm as N) significantly
      increased Ascaris egg inactivation at pH 9 and 11, and the ovicidal effect was
      directly related to the concentration of the uncharged NH3 species. Increasing
      temperatures (32-52 degrees C) caused increased inactivation at all pH levels and
      ammonia concentrations. The current EPA treatment requirements to produce Class A
      biosolids by alkaline treatment have temperature, pH, and time requirements, but
      do not account for the effectof differences in ammonia concentration on
      inactivation. To illustrate the potential savings in temperature and pH that
      could be achieved when accounting for ammonia inactivation, the combinations of
      ammonia concentration, temperature, and pH neededto achieve 99% inactivation
      after 72 h were determined. The presence of ammonia at concentrations encountered
      in sludges and feces (up to 8000 ppm as N) allowed for 99% egg inactivation to be
      achieved at temperatures up to 14 degrees C lower than ammonia-free controls.
      Thus, environmentally relevant concentrations of ammonia may significantly
      increase the rate of Ascaris egg inactivation during alkaline stabilization.

PMID- 16295856
TI  - Kinetic studies of synthetic metaschoepite under acidic conditions in batch and
      flow experiments.
AB  - The weathering and corrosion of depleted uranium (DU) forms a complex series of
      oxidation reactions, ultimately resulting in metaschoepite, UO3.2H2O. The present
      work focused on studying the dissolution rate of synthetic UO3. 2H2O using batch
      and flow-through reactors. Under acidic conditions (pH = 4.4-5.4), atmospheric
      CO2, room temperature, and 0.1 mionic strength,the log solubility product, log
      Ksp = 5.26 at equilibrium and a pH-dependent rate law Ro = (0.30 +/-
      0.15)[H+]0.83+/-0.1 were established. For consistency, these results were
      incorporated into the computer program PHREEQC 2.6, and the experimental
      conditions were simulated. There is generally good agreement between the
      experimental results and the modeled results. Batch experiments revealed a fast
      dissolution rate of UO3.2H20 in the first hour, followed by fluctuations in
      uranium concentration before equilibrium was attained after 3000 h.

PMID- 16295857
TI  - Aqueous atmospheric chemistry: formation of 2,4-dinitrophenol upon nitration of 2
      nitrophenol and 4-nitrophenol in solution.
AB  - Field studies have shown that the powerful phytotoxic agent 2,4-dinitrophenol is
      very likely to form in the atmospheric aqueous phase upon nitration of 2
      nitrophenol or 4-nitrophenol. However, until now, the nitration pathway and the
      relative importance of the two mononitrophenols as sources of 2,4-dinitrophenol
      were not known. The present study shows that 2,4-dinitrophenol formation from
      mononitrophenols can take place upon photolysis and photooxidation of
      nitrite/nitrous acid (NO2-/HONO) and that nitrogen dioxide plays a key role in
      the process. A possible pathway might be the reaction between light-excited
      mononitrophenols (both 2- and 4-isomers) and nitrogen dioxide, in the presence of
      oxygen. As an alternative, nitration might involve *NO3 + *NO2. Possible sources
      of nitrogen dioxide in the atmospheric aqueous phase are dissolution from the gas
      phase and oxidation of NO2-. In the latter case, however, it is necessary that
      NO2- oxidation is faster than the oxidation of mononitrophenols. This would
      happen, for instance, in the presence of hematite under irradiation. Radiation
      absorption and scattering by hematite would also inhibit the direct photolysis of
      nitrophenols. The formation rate and the yield of 2,4-dinitrophenol are slightly
      higher when starting from 2-nitrophenol than those from 4-nitrophenol, but they
      are compensated by the higher concentration of 4-nitrophenol in the atmospheric
      aqueous phase.

PMID- 16295858
TI  - Effect of natural organic substances on the surface and adsorptive properties of
      environmental black carbon (char): pseudo pore blockage by model lipid components
      and its implications for N2-probed surface properties of natural sorbents.
AB  - Black carbon (BC; char and soot) particles emitted to the environment typically
      are formed with high microporosity and surface area, properties that are
      responsible for their presumed important role in adsorption of anthropogenic
      organic compounds in soils and sediments. An issue that has received little
      direct attention is the possibility that naturally occurring organic matter
      attenuates the surface activity of BC. We found that simulated "aging" of
      prepared wood char particles in a soil-water suspension leads to a strong decline
      in char total surface area (TSA) by N2 adsorption at 77 K with BET analysis and a
      more modest decline in affinity for dissolved benzene. To help determine the
      underlying cause, we measured the effects of adsorbed natural lipids or lipid
      fractions of humic substances, modeled by triglycerides of a commercial vegetable
      oil. With increasing lipid loading (up to 40% by char weight) from aqueous
      mixtures, N2 TSA was strongly suppressed (up to 100-fold), while CO2 cumulative
      surface area (CSA, 0-1.4 nm) at 273 K and benzene adsorption at 293 K were hardly
      affected. In addition, the rate of CO2 adsorption was retarded. We propose that
      externally adsorbed lipid molecules occupy pore throats with access to interior
      pore networks. At 77 K, as opposed to the higher temperatures, lipid chains are
      too inflexible to allow passage of adsorbate. It is concluded that benzene
      adsorption to char predominates at interior pore sites and does not correlate
      with N2-probed micropore properties when the char accrues pore-blocking
      substances from the surroundings. The findings question the suitability of N2 for
      probing hydrophobic microporosity of BC in soils and sediments.

PMID- 16295859
TI  - Formation of bromochlorodibenzo-p-dioxins and furans from the high-temperature
      pyrolysis of a 2-chlorophenol/2-bromophenol mixture.
AB  - The homogeneous, gas-phase pyrolytic thermal degradation of a 50:50 mixture of 2
      bromophenol and 2-chlorophenol was studied in a 1 cm i.d., fused silica flow
      reactor at a total concentration of 88 ppm, reaction time of 2.0 s, and
      temperatures from 300 to 1000 degrees C. Observed products included (in
      decreasing yield) naphthalene, dibenzo-p-dioxin (DD), phenol, dibenzofuran (DF),
      bromobenzene, chloronaphthalene, 4-bromo-6-chlorodibenzofuran (4-B,6-CDF),
      bromonaphthalene, benzene, 4,6-dichlorodibenzofuran (4,6-DCDF), chlorobenzene, 4
      monobromodibenzofuran (4-MBDF), 4-monochlorodibenzofuran (4-MCDF), 1-mono
      bromodibenzo-p-dioxin (1-MBDD), 2-chloro,4-bromophenol, 2,4-dibromophenol, and 2
      bromo-4-chlorophenol. Unlike the case for the pyrolysis of pure 2-chlorophenol,
      4,6-DCDF was observed, but the analogous 4,6-DBDF remained undetected similar to
      the individual results with 2-MBP. This indicates that the presence of bromine
      increases the concentration of chlorine atoms available for the formation of 4,6
      DCDF. Due to bromine atoms acting as better leaving groups than chlorine atoms,
      the yield of DD was increased over that observed for the pyrolysis of 2
      chlorophenol. The addition of bromine to a chlorinated hydrocarbon system results
      in an increase in the total yield of PCDD/Fs as well as PBDD/Fs and mixed
      PBCDD/Fs due to the ease of bromine elimination reactions as well as an increase
      of the chlorine atom concentration.

PMID- 16295860
TI  - Influence of calcite and dissolved calcium on uranium(VI) sorption to a hanford
      subsurface sediment.
AB  - The influence of calcite and dissolved calcium on U(VI) adsorption was
      investigated using a calcite-containing sandy silt/clay sediment from the U. S.
      Department of Energy Hanford site. U(VI) adsorption to sediment, treated
      sediment, and sediment size fractions was studied in solutions that both had and
      had not been preequilibrated with calcite, at initial [U(VI)] = 10(-7)-10(-5)
      mol/L and final pH = 6.0-10.0. Kinetic and reversibility studies (pH 8.4) showed
      rapid sorption (30 min), with reasonable reversibility in the 3-day reaction
      time. Sorption from solutions equilibrated with calcite showed maximum U(VI)
      adsorption at pH 8.4 +/- 0.1. In contrast, calcium-free systems showed the
      greatest adsorption at pH 6.0-7.2. At pH > 8.4, U(VI) adsorption was identical
      from calcium-free and calcium-containing solutions. For calcite-presaturated
      systems, both speciation calculations and laser-induced fluorescence
      spectroscopic analyses indicated that aqueous U(VI) was increasingly dominated by
      Ca2UO2(CO3)3(0)(aq) at pH < 8.4 and thatformation of Ca2UO2(CO3)3(0)(aq) is what
      suppresses U(VI) adsorption. Above pH 8.4, aqueous U(VI) speciation was dominated
      by UO2(CO3)3(4-) in all solutions. Finally, results also showed that U(VI)
      adsorption was additive in regard to size fraction but not in regard to mineral
      mass: Carbonate minerals may have blocked U(VI) access to surfaces of higher
      sorption affinity.

PMID- 16295861
TI  - The influence of natural organic matter rigidity on the sorption, desorption, and
      competitive displacement rates of 1,2-dichlorobenzene.
AB  - The influence of natural organic matter (NOM) rigidity on the sorption,
      desorption, and competitive displacement rates of 1,2-Dichlorobenzene (1,2-DCB)
      was evaluated using batch reactor experiments with two surface soils (Yolo and
      Forbes) and a shale (Ohio). Previous characterization suggests that the shale NOM
      is the most reduced and condensed, the Yolo soil is the most oxidized and
      amorphous, and Forbes soil has an intermediate NOM structure. The rate study for
      each sorbent was conducted under the same reactor parameters, and 1,2-DCB mass
      transfer rates were determined using the distributed first-order mass-transfer
      rate model based on the gamma probability density function. To measure
      competitive displacement rates, 1,2,4-trichlorobenzene (1,2,4-TCB) was delivered
      as a competitor after 34 days pre-equilibration. Higher fractions of contaminant
      subject to instantaneous mass transfer and much faster rates of approach to
      apparent sorption equilibrium are found in Yolo soil when compared with Forbes
      soil and the shale. The size of the instantaneously desorbing fraction thus
      appears inversely related to the hard carbon fraction. In the NOM compartment
      where mass transfer is rate-limited, rate coefficient distributions are shifted
      toward lower rates for desorption and competitive displacement of 1,2-DCB in Ohio
      shale, followed by Forbes soil. Sorption and desorption rate distributions are
      almost the same for the shale, while desorption rates are a few times greater
      than sorption rates in Yolo and Forbes soils. Mass-transfer coefficients for
      competitive displacement are considerably slower than those for desorption in
      Forbes soil and the shale. However, the mass-transfer rates for the two processes
      seem to be similar in Yolo soil, which has a NOM matrix comprising a relatively
      larger soft organic carbon fraction. The concept of "solute induced softening" is
      discussed as a mechanistic rationale for the experimental observations.

PMID- 16295862
TI  - Modeling aqueous ozone/UV process using oxalic acid as probe chemical.
AB  - A kinetic model that describes the removal of organic pollutants by an ozone/UV
      process is described. Oxalic acid, which reacts with a very low rate constant
      with ozone and relatively high rate constant with hydroxyl radical (OH*), was
      used as the probe chemical to model the process. The model was verified by
      experimental data on concentrations of oxalic acid and hydrogen peroxide (H202)
      under various experimental conditions, i.e., ozone gas dosage, UV light
      intensity, and varying oxalic acid concentrations.

PMID- 16295863
TI  - Model prognoses for future acidification recovery of surface waters in norway
      using long-term monitoring data.
AB  - During the past 20 years, acid deposition in Europe has decreased by more than
      60%, yet still a large number of lakes and streams in southern Norway have not
      recovered to a water quality sufficient to support sustainable populations of
      trout or salmon. Long-term (30 years) monitoring data were used hereto constrain
      the calibration of the acidification model MAGIC to three Norwegian calibrated
      catchments. The model accounted for 60-80% of the variance in the year-to-year
      variations in concentrations of most of the major ions in streamwater. The
      results support the use of the lumped parameter acid neutralizing capacity (ANC)
      to link chemical parameters to biological response, as the calibration efficiency
      for ANC is considerably higher than for other biologically important parameters
      such as inorganic aluminum (Al(n+)) and pH. Three different scenarios for future
      deposition of sulfur were run: current legislation, maximum feasible reductions,
      and an illustrative scenario removing all anthropogenic deposition. These
      analyses show that much of the potential improvement in water quality has already
      occurred and that only limited further improvement can be expected from the
      current legislation. The current legislation is unlikely to produce ANC values
      sufficiently high to allow self-reproducing populations of trout at two of the
      three sites. Most of the response in water chemistry to reduced acid deposition
      has been rapid; the water chemical responses largely occur the same year or a few
      years after reduction in the input. The soil pool of exchangeable base cations
      depleted during 150 years of acid deposition, however, requires several centuries
      for replenishment. The uncertainties in future predictions come from several
      factors, such as future nitrogen dynamics and impacts from changes in seasalt and
      precipitation events. The differences in future water chemistry predicted from
      changed seasalt deposition or nitrogen dynamics are larger that the differences
      between different deposition scenarios. Hence, these factors must be included in
      future assessments of recovery from acidification.

PMID- 16295864
TI  - Reconciling trajectory ensemble receptor model results with emissions.
AB  - Several approaches have been developed that use ensembles of air parcel back
      trajectories to identify likely source regions for contaminants observed at a
      downwind receptor site. Although the results of these models have appeared to
      provide results that agree with known sources, there have not been efforts to
      make direct comparisons between the results of such analyses with emissions
      inventories. In this paper, the results of residence time analysis (RTA) of data
      from Underhill, VT and from Brigantine, NJ are compared to the average estimated
      emissions of coal- and oil-fired power plants. Excellent correspondence was found
      between the areas of highest probability identified in the trajectory ensemble
      analyses and the averaged emission intensities.

PMID- 16295865
TI  - Real-time measurements of SO2, H2CO, and CH4 emissions from in-use curbside
      passenger buses in New York City using a chase vehicle.
AB  - The Aerodyne Mobile Laboratory "chased" in-use curbside passenger buses operated
      by various operators in New York City. With the cooperation of New York State's
      Metropolitan Transit Authority, the relationships between the emissions of the
      several gas-phase species and particulate loadings were investigated across
      several bus technologies, bus types, and fuels (diesel, ultralow sulfur diesel,
      and compressed natural gas, CNG). The CNG buses followed did not employ an
      oxidation catalyst. The buses characterized were not prescreened in any fashion
      and were measured while deployed on their normal in-service routes. This paper
      focuses on the fuel-based mass emissions of SO2, H2CO, and CH4, measured using
      tunable infrared laser differential absorption spectroscopy. Sulfur dioxide
      emissions from buses known to be burning ultralow sulfur diesel (<30 ppm(m) S)
      were 16 times lower than those from buses burning normal commercial diesel fuel,
      nominally less than 300 ppm(m) sulfur. Emissions of formaldehyde and methane from
      in-use CNG buses were approximately 15 times greater than those from diesel
      powered buses.

PMID- 16295867
TI  - Assessing the potential for re-emission of mercury deposited in precipitation
      from arid soils using a stable isotope.
AB  - A solution containing 198Hg in the form of HgCl2 was added to a 4 m2 area of
      desert soils in Nevada, and soil Hg fluxes were measured using three dynamic flux
      chambers. There was an immediate release of 198Hg after it was applied, and then
      emissions decreased exponentially. Within the first 6 h after the isotope was
      added to the soil, approximately 12 ng m(-2) of 198Hg was emitted to the
      atmosphere, followed by a relatively steady flux of the isotope at 0.2 +/- 0.2 ng
      m(-2) h(-1) for the remainder of the experiment (62 days). Over this time,
      approximately 200 ng m(-2) or 2% of the 198Hg isotope was emitted from the soil,
      and we estimate that approximately 6% of the isotope would be re-emitted in a
      year's time. During the experiment, dry deposition of elemental Hg from the
      atmosphere was measured with an average deposition rate of 0.2 +/- 0.1 ng m(-2)
      h(-1). Emission of ambient Hg from the soil was observed after soil wetting with
      the isotope solution and after a storm event. However, the added moisture from
      the storm event did not affect 198Hg flux. Results suggest that in this desert
      environment, where there is limited precipitation, Hg deposited by wet processes
      is not readily re-emitted and that dry deposition of elemental Hg may be an
      important process.

PMID- 16295866
TI  - Real-time measurements of nitrogen oxide emissions from in-use New York City
      transit buses using a chase vehicle.
AB  - New diesel engine technologies and alternative fuel engines are being introduced
      into fleets of mass transit buses to try to meet stricter emission regulations of
      nitrogen oxides and particulates: Real-time instruments including an Aerodyne
      Research tunable infrared laser differential absorption spectrometer (TILDAS)
      were deployed in a mobile laboratory to assess the impact of the implementation
      of the new technologies on nitrogen oxide emissions in real world driving
      conditions. Using a "chase" vehicle sampling strategy, the mobile laboratory
      followed target vehicles, repeatedly sampling their exhaust. Nitrogen oxides from
      approximately 170 in-use New York City mass transit buses were sampled during the
      field campaigns. Emissions from conventional diesel buses, diesel buses with
      continuously regenerating technology (CRT), diesel hybrid electric buses, and
      compressed natural gas (CNG) buses were compared. The chase vehicle sampling
      method yields real world emissions that can be included in more realistic
      emission inventories. The NO, emissions from the diesel and CNG buses were
      comparable. The hybrid electric buses had approximately one-half the NOx
      emissions. In CRT diesels, NO2 accounts for about one-third of the NOx emitted in
      the exhaust, while for non-CRT buses the NO2 fraction is less than 10%.

PMID- 16295868
TI  - Soot emissions from spherical droplet flames for mixtures of JP8 and tripropylene
      glycol monomethyl ether.
AB  - The combustion of JP8 (a kerosene-based fuel) mixed with up to 20% (volume)
      tripropylene glycol monomethyl ether (TPGME, CH3[CH2CH(CH3)O]3OH) is studied to
      examine the influence of composition on soot dynamics for the configuration of an
      isolated and stationary droplet burning with nearly spherical symmetry. The
      spherical droplet flame is characterized by a one-dimensional transport process
      with a concentric flame and droplet, and a sooting configuration for which the
      soot aggregates are trapped between the droplet and flame in a "shell" or
      "cloud". Sooting tendencies are inferred from photographic documentation of the
      droplet burning process and are found to be in the approximate order JP8 > JP8 +
      10% TPGME > JP8 + 20% TPGME. At 20% the soot cloud all but disappears. The
      maximum soot aggregate diameter is 80 (+/-17) nm, independent of composition.
      Preferential vaporization is pronounced as evidenced by a plateau in the
      evolution of the droplet diameter (squared) which indicates a dominant influence
      of TPGME over other constituents in JP8 that makes JP8/TPGME behave almost like a
      binary mixture despite the highly multicomponent nature of the JP8/TPGME blend. A
      scaling relationship for flame, soot cloud, and droplet diameters is shown to
      consolidate the measurements onto a single curve.

PMID- 16295869
TI  - Ozonation of carbamazepine in drinking water: identification and kinetic study of
      major oxidation products.
AB  - Kinetics and product formation of the anti-epileptic drug carbamazepine (CBZ)
      were investigated in lab-scale experiments during reactions with ozone and OH
      radicals. Ozone reacts rapidly with the double bond in CBZ, yielding several
      ozonation products containing quinazoline-based functional groups. The structures
      for three new oxidation products were elucidated using a combination of mass
      spectrometric and NMR techniques. The three products were determined to be 1-(2
      benzaldehyde)-4-hydro-(1H,3H)-quinazoline-2-one (BQM), 1-(2-benzaldehyde)-(1H,3H)
      quinazoline-2,4-dione (BQD), and 1-(2-benzoic acid)-(1H,3H)-quinazoline-2,4-dione
      (BaQD). Additional kinetic studies of the ozonation products showed very slow
      subsequent oxidation kinetics with ozone (second-order rate constants, kO3 =
      approximately 7 M(-1)s(-1) and approximately 1 M(-1)s(-1) at pH = 6 for BQM and
      BQD, respectively). Rate constants for reactions with OH radicals, kOH, were
      determined as approximately 7 x 10(9) M(-1)s(-1) for BQM and approximately 5 x
      10(9)M(-1)s(-1) for BQD. Thus, mainly reactions with OH radicals lead to their
      further oxidation. A kinetic model including ozone and OH radical reactions
      allows a prediction of the time-dependent product distribution during ozonation
      of natural waters. In Rhine River water, CBZ spiked at 500 ng/L was completely
      oxidized by ozone with applied doses > or =0.3 mg/L. To confirm that the two
      major ozonation products BQM and BQD are produced as a result of the ozonation of
      a CBZ-containing natural water, Lake Zurich water samples were spiked with CBZ (1
      microM, 236 microg/L). The oxidation products were identified via LC-UV.
      Concentrations of 0.48 and 0.15 microM for BQM and BQD, respectively, were
      measured for an ozone dose of 1.9 mg/L. BQM and BQD were also identified in
      ozonated water from a German waterworks containing CBZ in its raw water with 0.07
      0.20 microg/L. Currently, there are no data available on the biological effects
      of the formed oxidation products.

PMID- 16295870
TI  - Evaluation of PCDD/F congener partition in vapor/solid phases of waste
      incinerator flue gases.
AB  - Activated carbon injection (ACI) is commonly used to control PCDD/F
      (polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans) emissions
      from stationary sources. In this study, the characteristics of PCDD/Fs emitted
      from one municipal waste incinerator (MWI) and two industrial waste incinerators
      (IWI-1 and IWI-2) that apply activated carbon systems for controlling the
      emissions are investigated via intensive stack sampling. MWI and IWI-1 are
      equipped with ACI and bag filters (BF) while IWI-2 is equipped with a fixed
      activated carbon bed (FCB). Results indicate that most PCDD/Fs in flue gas
      downstream of ACI+BF exist in vapor phase (over 90%) while most PCDD/ Fs exist in
      solid phase (over 60%) downstream of FCB. For MWI and IWI-1, the removal
      efficiencies of vapor and solid-phase PCDD/Fs are 98.5-99.6% and 99.8-99.9%,
      respectively. In addition,the removal efficiencies of vapor- and solid-phase
      PCDD/Fs are 84.5% and -13.4% in IWI-2, respectively. The results also indicate
      that the partition of vapor/solid-phase PCDD/F is affected by the type of the air
      pollutant control devices (APCDs) applied upstream and the particulate matter
      concentration in flue gas. On the basis of the sampling results of waste
      incinerators, this study preliminarily establishes the equations for predicting
      vapor/solid-phase PCDD/F partition in flue gases downstream of various APCDs
      including cyclone (CY), electrostatic precipitator (EP), FCB, ACI+BF, and
      selective catalytic reduction system (SCR).

PMID- 16295871
TI  - Arsenic removal from Bangladesh tube well water with filter columns containing
      zerovalent iron filings and sand.
AB  - Arsenic removal is often challenging due to high As(III), phosphate, and silicate
      concentrations and low natural iron concentrations. Application of zerovalent
      iron is promising, as metallic iron is widely available. However, removal
      mechanisms remained unclear and currently used removal units with iron have not
      been tested systematically, partly due to their large size and long operation
      time. This study investigated smaller filter columns with 3-4 filters, each
      containing 2.5 g of iron filings and 100-150 g of sand. At a flow rate of 1 L/h,
      these columns were able to treat 75-90 L of well water with 440 microg/L As, 1.8
      mg/L P, 4.7 mg/L Fe, 19 mg/L Si, and 6 mg/L dissolved organic carbon (DOC) to
      below 50 microg/L As(tot), without addition of an oxidant. As(III) was oxidized
      in parallel to oxidation of corrosion-released Fe(II) by dissolved oxygen and
      sorbed on the forming hydrous ferric oxides (HFO). The open filter columns
      prevented anoxic conditions. DOC did not appear to interfere with arsenic
      removal. Manganese was reduced after a slight initial increase from 0.3 mg/L to
      below 0.1 mg/L. About 100 mg of Fe(0)/L of water was required, 3-5 times less
      than that for larger units with sand and iron turnings.

PMID- 16295872
TI  - Removal of arsenic from groundwater by zerovalent iron and the role of sulfide.
AB  - Several recent investigations have shown encouraging potential for the removal of
      arsenic (As) from groundwater by granular zerovalent iron (Fe0). In contrast to
      previous studies conducted, we have investigated the applicability of this method
      and the nature of As bonding under conditions with dissolved sulfide. Three
      column tests were performed over the period of 1 year using solutions with either
      As(V) or As(II) (2-200 mg/L) in the input solution. Arsenic outflow
      concentrations decreased from initially 30-100 microg/L to concentrations of
      below 1 microg/L with time. XANES (X-ray absorptions near edge structure) and
      EXAFS (expanded X-ray absorption fine structure) spectra indicated that As in the
      solid phase is not only directly coordinated with oxygen, as is the case in
      adsorbed or coprecipitated arsenite and arsenate. Samples with high sulfur
      content showed additional bonding, for which Fourier transformations of EXAFS
      data exhibited a peak between 2.2 and 2.4 A. This bonding most likely originated
      from the direct coordination of sulfur or iron with As, which was incorporated in
      iron sulfides orfrom adsorbed thioarsenites. The formation of this sulfide
      bonding supports the removal of As by Fe0 because sulfide production by microbial
      sulfate reduction is ubiquitous in permeable reactive barriers composed of Fe0.

PMID- 16295873
TI  - Sorption and desorption of arsenic to ferrihydrite in a sand filter.
AB  - Elevated arsenic concentrations in drinking water occur in many places around the
      world. Arsenic is deleterious to humans, and consequently, As water treatment
      techniques are sought. To optimize arsenic removal, sorption and desorption
      processes were studied at a drinking water treatment plant with aeration and sand
      filtration of ferrous iron rich groundwater at Elmevej Water Works, Fensmark,
      Denmark. Filter sand and pore water were sampled along depth profiles in the
      filters. The sand was coated with a 100-300 microm thick layer of porous Si-Ca-As
      contaning iron oxide (As/Fe = 0.17) with locally some manganese oxide. The iron
      oxide was identified as a Si-stabilized abiotically formed two-line ferrihydrite
      with a magnetic hyperfine field of 45.8 T at 5 K. The raw water has an As
      concentration of 25 microg/L, predominantly as As(II). As the water passes
      through the filters, As(III) is oxidized to As(V) and the total concentrations
      drop asymptotically to a approximately 15 microg/L equilibrium concentration. Mn
      is released to the pore water, indicating the existence of reactive manganese
      oxides within the oxide coating, which probably play a role for the rapid As(III)
      oxidation. The As removal in the sand filters appears controlled by sorption
      equilibrium onto the ferrihydrite. By addition of ferrous chloride (3.65 mg of
      Fe(II)/L) to the water stream between two serially connected filters, a 3
      microg/L As concentration is created in the water that infiltrates into the
      second sand filter. However, as water flow is reestablished through the second
      filter, As desorbs from the ferrihydrite and increases until the 15 microg/L
      equilibrium concentration. Sequential chemical extractions and geometrical
      estimates of the fraction of surface-associated As suggest that up to 40% of the
      total As can be remobilized in response to changes in the water chemistry in the
      sand filter.

PMID- 16295874
TI  - Magnetically agitated photocatalytic reactor for photocatalytic oxidation of
      aqueous phase organic pollutants.
AB  - A magnetically agitated photocatalytic reactor (MAPR) has been developed and
      assessed for oxidation of phenol. The MAPR uses a titanium dioxide composite
      photocatalyst with a ferromagnetic barium ferrite core. The catalyst motion was
      controlled with a dual-component magnetic field. First, a permanent magnet above
      the reactor provided a static magnetic field to counteract the force of gravity,
      hence increasing catalyst exposure to UV. Second, an alternating magnetic field
      generated by a solenoid was used to agitate the catalyst, thus increasing mass
      transfer between pollutants and byproducts to the catalyst. Optimal performance
      of the MAPR was achieved with the permanent magnet present and 1 A of alternating
      current to the solenoid between 20 and 80 Hz. Operating with a 60-Hz signal at 1
      A with the permanent magnet present and 100 mg of catalyst, the system reduced an
      11 mg/L phenol concentration by97% and decreased nonpurgeable dissolved organic
      carbon by 93% in 7 h using three 8-W 365-nm peak UV lamps.

PMID- 16295875
TI  - Model assessment of biogeochemical controls on dissolved organic carbon
      partitioning in an acid organic soil.
AB  - A chemical model (constructed in the ORCHESTRA modeling framework) of an organic
      soil horizon was used to describe soil solution data (10 cm depth) and assess if
      seasonal variations in soil solution dissolved organic carbon (DOC) could be
      explained by purely abiotic (geochemical controls) mechanisms or whether factors
      related to biological activity are needed. The NICA-Donnan equation is used to
      describe the competitive binding of protons and cations and the charge on soil
      organic matter. Controls on organic matter solubility are surface charge and a
      parameter, gamma, that accounts for the distribution of humic molecules between
      hydrophobic and hydrophilic fractions. Calculations show that the variations in
      solute chemistry alone are not sufficient to account for the observed variations
      of DOC, but factors that alter gamma, such as biological activity, are. Assuming
      that DOC in organic soils is derived from soluble humic material and that gamma
      is modified seasonally due to biological activity (with monthly soil temperature
      used as a surrogate for biological activity) we are able to model the observed
      seasonality of soil solution DOC over a 10-year period. Furthermore, with modeled
      DOC coupled to other geochemical processes we also model soil solution pH and Al
      concentrations.

PMID- 16295876
TI  - Evolution of technetium speciation in reducing grout.
AB  - Cementitious waste forms (CWFs) are an important component of the strategy to
      stabilize nuclear waste resulting from plutonium production by the U. S.
      Department of Energy. Technetium (99Tc) is an abundant fission product of
      particular concern in CWFs because of the high solubility and mobility of
      Tc(VII), pertechnetate (TcO4-), the stable form of technetium in aerobic
      environments. CWFs can more effectively stabilize 99Tc if they contain additives
      that chemically reduce mobile TcO4- to immobile Tc(IV) species. The 99Tc leach
      rate of reducing CWFs that contain Tc(IV) is much lower than that for CWFs that
      contain TcO4-. Previous X-ray absorption fine structure studies showed that
      Tc(IV) species were oxidized to TcO4- in reducing grout samples prepared on a
      laboratory scale. Whether the oxidizer was atmospheric O2 or NO3- in the waste
      simulant was not determined. In actual CWFs, rapid oxidation of Tc(IV) by NO3-
      would be of concern, whereas oxidation by atmospheric O2 would be of less concern
      due to the slow diffusion and reaction of O2 with the reducing CWF. To address
      this uncertainty, two series of reducing grouts were prepared using TcO4-
      containing waste simulants with and without NO3-. In the first series of samples,
      referred to as "permeable samples", the TcO4- was completely reduced using Na2S,
      and the samples were sealed in cuvettes made of polystyrene, which has a
      relatively large O2 diffusion coefficient. In these samples, all of the
      technetium was initially present as a Tc(IV) sulfide compound, TcSx, which was
      characterized by extended X-ray absorption fine structure (EXAFS) spectroscopy.
      The EXAFS data is consistent with a structure consisting of triangular clusters
      of Tc(IV) centers linked together through a combination of disulfide and sulfide
      bridges as in MoS3. From the EXAFS model, the stoichiometry of TcSx is TC3S10,
      which is presumably the compound generally referred to as "Tc2S7". The TcSX
      initially present in the permeable samples was steadily oxidized over 4 years. In
      the second series of samples, called "impermeable samples", the TcO4- was not
      initially completely reduced, and the groutsamples were sealed in cuvettes made
      of poly-(methyl methacrylate), which has a small O2 diffusion coefficient. In the
      impermeable samples, the remaining TcO4- continued to be reduced, presumably by
      blast furnace slag in the grout, as the samples aged. When the impermeable
      samples were opened and exposed to atmosphere, the lower-valent technetium
      species were rapidly oxidized to TcO4-.

PMID- 16295877
TI  - Electrochemical alkaline Fe(VI) water purification and remediation.
AB  - Fe(VI) is an unusual and strongly oxidizing form of iron, which provides a
      potentially less hazardous water-purifying agent than chlorine. A novel on-line
      electrochemical Fe(VI) water purification methodology is introduced. Fe(VI)
      addition had been a barrier to its effective use in water remediation, because
      solid Fe(VI) salts require complex (costly) syntheses steps and solutions of
      Fe(VI) decompose. Online electrochemical Fe(VI) water purification avoids these
      limitations, in which Fe(VI) is directly prepared in solution from an iron anode
      as the FeO42- ion, and is added to the contaminant stream. Added FeO42-
      decomposes, by oxidizing a wide range of water contaminants including sulfides
      (demonstrated in this study) and other sulfur-containing compounds, cyanides
      (demonstrated in this study), arsenic (demonstrated in this study), ammonia and
      other nitrogen-containing compounds (previously demonstrated), a wide range of
      organics (phenol demonstrated in this study), algae, and viruses (each previously
      demonstrated).

PMID- 16295878
TI  - Tubular microbial fuel cells for efficient electricity generation.
AB  - A tubular, single-chambered, continuous microbial fuel cell (MFC) that generates
      high power outputs using a granular graphite matrix as the anode and a
      ferricyanide solution as the cathode is described. The maximal power outputs
      obtained were 90 and 66 W m(-3) net anodic compartment (NAC) (48 and 38 W m(-3)
      total anodic compartment (TAC)) for feed streams based on acetate and glucose,
      respectively, and 59 and 48 W m(-3) NAC for digester effluent and domestic
      wastewater, respectively. For acetate and glucose, the total Coulombic conversion
      efficiencies were 75 +/- 5% and 59 +/- 4%, respectively, at loading rates of 1.1
      kg chemical oxygen demand m(-3) NAC volume day(-1). When wastewater was used, of
      the organic matter effectively removed (i.e., 22% at a loading of 2 kg organic
      matter m(-3) NAC day(-1)), up to 96% was converted to electricity on a Coulombic
      basis. The lower overall efficiency of the wastewater-treating reactors is
      related to the presence of nonreadily biodegradable organics and the interference
      of alternative electron acceptors such as sulfate present in the wastewater. To
      further improve MFCs, focus has to be placed on the enhanced conversion of
      nonrapidly biodegradable material and the better directing of the anode flow
      toward the electrode instead of to alternative electron acceptors. Also the use
      of sustainable, open-air cathodes is a critical issue for practical
      implementation.

PMID- 16295879
TI  - Toxicokinetics of 14C-atrazine and its metabolites in stage-66 Xenopus laevis.
AB  - Several recent studies have focused on the toxicodynamic implications of
      amphibian exposure to the commonly used herbicide atrazine (2-chloro-4-ethylamine
      6-isopropylamino-s-triazine). These studies are an important part of the risk
      assessment process; however, the underlying mechanisms of atrazine toxicodynamics
      are lacking. In an attempt to more fully describe atrazine exposure, the
      toxicokinetics of atrazine were studied in stage-66 Xenopus laevis larvae. The
      absorption, distribution, and excretion capacity of these larvae were found to be
      comparable to those observed in fish. The calculated bioconcentration factor
      (BCF) was 1.5-1.6 mLwater/glarvae, and by use of whole-body autoradiography, the
      radiolabel was found to be concentrated in the gall bladder and gastrointestinal
      tract. Elimination of atrazine was rapid with a half-life of 48 min. The high
      metabolic capacity of stage-66 X. laevis larvae was demonstrated where, following
      8 h of exposure to 14C-atrazine, the percentages of atrazine and its metabolites
      deethyldeisopropylatrazine (DACT), deisopropylatrazine (DIA), and deethylatrazine
      (DEA) in larvae, determined by thin-layer chromatography, were 49.8% +/- 3.3%,
      9.8% +/- 2.1%, 16.1% +/- 2.5%, and 15.6% +/- 2.0%, respectively. An unknown
      metabolite(s) was also produced and accounted for the remaining proportion of the
      total body radioactive residues. This metabolite(s) is hypothesized to be a
      conjugate of either atrazine or one of its metabolites. These metabolites,
      namely, DIA, were responsible for the long elimination half-life (72 h) of the
      total body radioactive residues. These toxicokinetics data would provide better
      insights in the interpretation of toxicodynamic data.

PMID- 16295880
TI  - Identifying sources and biomagnification of persistent organic contaminants in
      biota from mountain streams of southwestern British Columbia, Canada.
AB  - We assessed whether biota occupying mountain streams accumulate and biomagnify
      remotely derived organic pollutants originating from atmospheric inputs to
      snowpack and glacial runoff and from marine sources introduced by migrating
      anadromous salmon. Several persistent organic pollutants including
      polychlorinated biphenyls (PCBs), p,p'-dichloro-diphenyl-dichloroethylene,
      hexachlorobenzene, and trans-nonachlor were commonly detected in benthic
      invertebrates, salmon fry (Oncorhynchus spp.), and eggs of an aquatic passerine,
      the American dipper (Cinclus mexicanus) from the Chilliwack River watershed,
      British Columbia, Canada. Total PCBs and several organochlorines (OCs)
      biomagnified from benthic invertebrate composites to salmon fry to dipper eggs.
      Invertebrate samples generally did not differ significantly in contaminant
      burdens between the river main stem where salmon are more abundant and higher
      elevation tributaries where the salmon density is lower. Concentrations of total
      OCs and total PCBs in dipper eggs were positively related to drainage basin area
      and collection year but not to elevation. No differences in PCB congener patterns
      existed between dipper egg samples from the Chilliwack watershed and other
      watersheds in southwestern British Columbia. However, principal component
      analysis revealed significant spatial differences in egg PCB congener patterns
      between the main Chilliwack River and the higher-elevation tributaries. This
      difference was primarily due to a greater occurrence of lower chlorinated PCB
      congeners (66 and 105) in dipper eggs collected from the tributaries and higher
      loadings of the more stable and persistent congeners (153, 138, 130, and 128) in
      eggs from the river main stem. The results suggest that atmospheric sources are
      the main contributor of contaminants detected in biota from the region and that
      biomagnification is a common pathway for accumulation in lotic predators such as
      the American dipper.

PMID- 16295881
TI  - Thiol and metal contents in periphyton exposed to elevated copper and zinc
      concentrations: a field and microcosm study.
AB  - Phytochelatins are metal-binding polypeptides produced by algae under metal
      exposure. The aim of this study was to investigate the effects of metal
      concentration variations in natural systems on periphyton at the biochemical
      level by analyzing its intracellular thiol content, in particular phytochelatins.
      To that purpose, two field campaigns were conducted in a stream subject to an
      increase of dissolved metal concentrations (particularly Cu and Zn) during rain
      events, which results in an increase of their accumulation in periphyton. At
      background metal concentrations, several thiols were detectable in periphyton,
      namely, glutathione (GSH), gamma-glutamylcysteine (gammaGluCys), phytochelatins
      (PC2), and some unidentified thiols, U1 and U2. Glutathione and gammaGluCys
      contents were found to vary independently of the rain, as well as U1 and U2,
      whereas the phytochelatin content increased during the rain events. To
      investigate whether Cu or Zn may be responsible for this increase, microcosm
      experiments were carried out with natural water enriched with Cu, Zn, and Cd
      separately, and Cu and Zn in combination. In this study, GSH, PC2, and U1 were
      also detected, but not gammaGluCys. An increase in accumulated Cu content did not
      induce any changes in thiol content, whereas an increase of the Zn content
      induced a decrease in GSH content and an increase in phytochelatin content. Zinc
      rather than Cu may thus induce a phytochelatin content increase in periphyton in
      the field studies. Addition of Cu and Zn in combination also induced an increase
      in phytochelatin content. Cadmium was found to be the most effective inducer,
      with the production of larger phytochelatins (PC3-4). This study is the first one
      to report changes in thiol content in periphyton in response to an increase of
      the metal concentration in natural freshwaters.

PMID- 16295882
TI  - Comment on "Semiempirical model for organic aerosol growth by acid-catalyzed
      heterogeneous reactions of carbonyls".

PMID- 16295883
TI  - Effects of mercury contaminated rice from typical chemical plant area in China on
      nitric oxide changes and c-fos expression of rats brain.
AB  - China is one of countries with the highest mercury production in the world. The
      Guizhou Province in Southwestern China is currently one of the world's most
      important mercury production areas. In order to study the neurotoxicity of rice
      from Qingzhen Chemical Plant area and probe into the signal transduction
      molecular mechanism of injury in rat brain stimulation by mercury contaminated
      rice. The rats were exposed to mercury contaminated rice for 20 d. Both of the
      measurements of NO and NOS were processed according to the protocol of the kit.
      The effect of Hg contaminated rice on the expression of c-fos mRNA in rat brain
      and the expression of c-FOS protein in cortex, hippocampus were observed using
      reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical
      methods. The results showed the neural transmitter NO and NOS in brain were
      significantly change between exposure groups and control group; the mercury
      polluted rice induced significantly the expression of c-fos mRNA; the c-FOS
      positive cells in hippocampus and cortex of exposure groups were significant
      different from control group (p < 0.01). It could be concluded that nitric oxide
      was involved in mercury contaminated rice induced immediate early gene c-fos
      expressions in the rat brain. Through food chain, local ecosystem and health of
      local people iave been deteriorated seriously by mercury. This serious situation
      will last a long period. In order to alleviate mercury pollution, more work needs
      to do.

PMID- 16295884
TI  - Controlled-release fertilizer (CRF): a green fertilizer for controlling non-point
      contamination in agriculture.
AB  - Fertilizers contribute greatly to high yields but also result in environmental
      non-point contamination, including the emission of greenhouse gas (N2O) and
      eutrophication of water bodies. How to solve this problem has become a serious
      challenge, especially for China as its high ecological pressure. Controlled
      release fertilizer(CRF) has been developed to minimize the contamination while
      keeping high yield and has become a green fertilizer for agriculture. Several
      CRFs made with special coating technology were used for testing the fertilizer
      effects in yield and environment through pot experiment and field trial. The
      result indicated that the CRFs had higher N use efficiency, thus reducing N loss
      through leaching and volatilization while keeping higher yields. Comparing with
      imported standard CRFs, the test on CRFs showed similar fertilizer effect but
      with much lower cost. CRFs application is becoming a new approach for minimizing
      non-point contamination in agriculture.

PMID- 16295885
TI  - Thermodynamics of phenanthrene partition into solid organic matter from water.
AB  - The thermodynamic behavior of organic contaminants in soils is essential to
      develop remediation technologies and assess risk from alternative technologies.
      Thermodynamics of phenanthrene partition into four solids(three soils and a
      bentonite) from water were investigated. The thermodynamics parameters (deltaH,
      deltaG degrees, deltaS degrees) were calculated according to experimental data.
      The total sorption heats of phenanthrene to solids from water ranged from -7.93
      to -17.1 kJ/mol, which were less exothermic than the condensation heat of
      phenanthrene-solid (i.e., -18.6 kJ/mol). The partition heats of phenanthrene
      dissolved into solid organic matter ranged from 23.1 to 32.2 kJ/mol, which were
      less endothermic than the aqueous dissolved heat of phenanthrene (i.e., 40.2
      kJ/mol), and were more endothermic than the fusion heat of phenanthrene-solid
      (i.e., 18.6 kJ/mol). The standard free energy changes, deltaG degrees, are all
      negative which suggested that phenanthrene sorption into solid was a spontaneous
      process. The positive values of standard entropy changes, deltaS degrees, show a
      gain in entropy for the transfer of phenanthrene at the stated standard state.
      Due to solubility-enhancement of phenanthrene, the partition coefficients
      normalized by organic carbon contents decrease with increasing system temperature
      (i.e., ln Koc = -0.284 ln S + 9.82 (n = 4, r2 = 0.992)). The solubility of
      phenanthrene in solid organic matter increased with increasing temperatures.
      Transports of phenanthrene in different latitude locations and seasons would be
      predicted according to its sorption thermodynamics behavior.

PMID- 16295886
TI  - Effect of nitrogen concentration in culture mediums on growth and enzyme
      production of Phanerochaete chrysosporium.
AB  - Effect of different nitrogen concentration in the mediums on growth and enzyme
      production of Phanerochaete chrysosporium was studied when glucose concentration
      was 10 g/L. The results showed that the medium contained 0.8 g/L ammonium
      tartrate is the best. It not only supply abundant nutrients for the growth of
      Phanerochaete chrysosporium, which make mycelia the best grow compared with the
      other medium, but also produce higher manganese-dependent peroxidase (Mnp) and
      laccase (Lac) activity. In addition, it is observed that the variation of mycelia
      surface is related to ligninolytic enzyme secreted by Phanerochaete
      chrysosporium. When the surface of mycelium pellets appeared burs, it predicts
      secondary metabolism begin. This experimentation demonstrated that when the ratio
      of carbon and nitrogen in nitrogen limited medium is equal to 100:8, growth and
      enzyme production of Phanerochaete chrysosporium is the best, it could achieve
      the maximum Mnp and Lac activity.

PMID- 16295887
TI  - Optimal turning method of composting regarding hygienic safety.
AB  - The new turning method was proposed and verified its effectiveness to pathogens
      by laboratory scale experiments. Considering the results obtained from the
      previous studies, it could be said that turning of a composting pile was
      essential in terms of hygienic aspects but the number of turning should be
      minimized. Effectiveness of inactivation was estimated for each composting run.
      From this estimation, turning by layers, which is different from conventional
      turning that mixes compost pile entirely, was proposed and investigated its
      performance by experiments. Composting operations with static pile method,
      complete mix (conventional) turning method, and proposed turning (layer turning)
      method were done and their effectiveness on inactivation of indicator
      microorganism was evaluated and compared. As results, the conventional turning
      method was not a proper method in terms of pathogen inactivation, whereas, the
      proposed turning method showed an excellent performance and should be employed in
      a composting operation.

PMID- 16295888
TI  - Effect of organic fractions on sorption properties of organic pollutants in
      sediments.
AB  - Humic substrates are a major fraction of sediment organic matters, and the
      sorption of hydrophobic organic chemicals by humic substrates influences their
      behavior and fate in sediment. In this paper, organic matters were divided into
      non-humic substrates and humic substrates. Non-humic substrates include acid
      leaching fraction, acid extracted fraction, and lipid; humic substrates were
      fractionated into Ca-binding-FA (fulvic acid), Ca-binding-HA (humic acid), oxide
      FA, oxide-HA, and humin. To study the effect of organic fractions on sorption
      properties, sorption kinetic and equilibrium sorption experiments of phenanthrene
      and pentachlorophenol (PCP) in five sediments were carried out. The results
      showed that the contents of acid leaching fraction and oxide-binding-HA were the
      main fractions to affect the sorption rate constant, and for the sorption
      capacity of phenanthrene, humin was the major fraction, followed by oxide-binding
      HA, oxide-binding-FA, and so on. While for PCP, the factors of influence on
      sorption capacity were mainly CEC, Ca-binding-FA, and Ca-binding-HA.

PMID- 16295889
TI  - Degradation characteristics of two Bacillus strains on the Microcystis
      aeruginosa.
AB  - The degradation kinetics of strains P05 and P07 and the degradation effects of
      mixed strain on Microcystis aeruginosa were studied. The results showed that: (1)
      The degradation processes of strains P05 and P07 on Microcystis aeruginosa
      accorded with the first-order reaction model when the range of Chl-a
      concentration was from 0 to 1500 microg/L. (2) The initial bacterium densities
      had a strong influence on the degradation velocity. The greater the initial
      bacterium density was, the faster the degradation was. The degradation velocity
      constants of P05 were 0.1913, 0.2175 and 0.3092 respectively, when bacterium
      densities were 4.8 x 10(5), 4.8 x 10(6), 2.4 x 10(7) cells/ml. For strain P07,
      they were 0.1509, 0.1647 and 0.2708. The degradation velocity constant of strain
      P05 was higher than that of P07 when the bacterium density was under 4.8 x 10(5)
      cells/ml, but the constant increasing of P07 was quicker than that of P05. (3)
      The degradation effects of P05 and P07 strains did not antagonize. When the
      concentration of Chl-a was high, the degradation effects of mixed strain excelled
      that of any single strains. But with the decrease of the Chl-a concentration,
      this advantage was not clear. When the concentration was less than 180 microg/L,
      the degradation effects of mixed were consistent with that of strain P07.

PMID- 16295890
TI  - Kinetics of photoelectrocatalytic degradation of humic acid using B2O3.TiO2/Ti
      photoelectrode.
AB  - An innovative photoelectrode, B2O3.TiO2/Ti electrode, was prepared by
      galvanostaticanodisation. The morphology and crystalline texture of the B2O3.TiO2
      film on electrode were examined by atomic force microscopy (AFM) and X-ray
      diffraction respectively. The examination results indicated that the anatase was
      the dominant component. The kinetics of photoelectrocatalytic (PEC) degradation
      of humic acid(HA) was investigated; the results demonstrated that effects from
      strongness to weakness on the photoelectrocatalytic degraded rate of humic acid:
      power of UV-lamp, area of TiO2 film, bias, original concentration of humic acid
      solution. The optimum conditions were power of UV-lamp 125 W, area of TiO2 film
      42.0 cm2, bias 1.4 V, original concentration of humic acid solution 5 mg/L in
      this PEC reaction system.

PMID- 16295891
TI  - Adsorption/desorption behavior between a novel amphoteric granular lignin
      adsorbent and reactive red K-3B in aqueous solutions.
AB  - A novel amphoteric granular lignin adsorbent (AGLA) was prepared using magnesium
      lignosulfonate as a raw material which was provided by a straw sulfite pulp mill
      in Guangdong Province, China. A reactive dye (red K-3B) was used as an adsorbate
      to investigate the adsorption behavior by static and mobile ways. The removal of
      reactive red K-3B was found to be initially pH and concentration dependent.
      Moreover, an increase of solution temperature ranging from 5 degrees C to 60
      degrees C helped to enhance the rate of intraparticle diffusion of adsorbate and
      changes in the size of the pores of the adsorbent and thus to reduce the
      adsorption time. The total breakthrough adsorption capacity was 531 mg/g, and the
      saturated adsorption capacity was 560 mg/g, which prevailed over the activated
      carbons evidently. The reactive red K-3B adsorbed on AGLA could be recovered with
      a mixture of alcohol, NaCl and HCl aqueous solutions. The recovery percentage
      could reach 92.4%.

PMID- 16295892
TI  - Bound 14C-metsulfuron-methyl residue in soils.
AB  - Bound residue(BR) of 14C-metsulfuron-methyl (14C-BR) in seven kinds of soil was
      significantly negative-related to soil pH and positive-related to the clay
      content during the initial 20 d of incubation, but only was significantly
      negative-related to soil pH after 30 d incubation. Again, the soil pH was found
      to be the dominant factor affecting BR formation from 14C-metsulfuron-methyl
      among the basic properties(soil pH, clay, OM and CEC etc.) of soil. The maximum
      content of 14C-BR in the 7 soils accounted for 19.3% - 52.6% of applied amount.
      In addition, the composition of the 14C-BR in fluvio marine yellow loamy (S7) at
      the 90 d of incubation was identified using the coupling technique of LC-MS and
      isotope tracing method. The results showed that the 14C-[2-amino-4-hydroxyl-6
      methyl-1, 3, 5]-triazine, 14C-[2-amino-4-methoxy-6-methyl-1, 3, 5]-triazine and
      14 C-metsulfuron-methyl parent compound constituted the main components of the BR
      derived from 14 C-metsulfuron-methyl in the S7. The relative percentage of the
      three compounds accounted for 41.4%, 35.8% and 19.3% of total recovery
      radioactivity, respectively. The results also indicated that a non-radioactive
      component, 2-methylformate-benzenesulfonyl-isocyanate, one of the degraded
      products of metsulfuron-methyl in soil, was also found to be one of the
      components of the BR. The parent compound in BR can well explain the phytotoxic
      effect on substitution crops caused by the BR derived from metsulfuron-methyl in
      soil.

PMID- 16295893
TI  - Simultaneous catalytic removal of NOx and diesel PM over La(0.9) K(0.1) CoO3
      catalyst assisted by plasma.
AB  - The simultaneous removal of NOx and particulate matter (PM) from diesel exhaust
      is investigated over a mixed metal oxide catalyst of La(0.9) K(0.1) CoO3 loaded
      on gamma-Al2O3 spherules with the assistant of plasma. It was found that NOx was
      reduced by PM in oxygen rich atmosphere, the CO2 and N2 were produced in the same
      temperature window without considering the N2 formed by plasma decomposition. As
      a result, the temperature for the PM combustion decreases and the reduction
      efficiency of NOx to N2 increases during the plasma process, which indicated that
      the activity of the catalyst can be improved by plasma. The NOx is decomposed by
      plasma at both low temperature and high temperature. Therefore, the whole
      efficiency of NOx conversion is enhanced.

PMID- 16295895
TI  - Growth responses of Picea mongolica seedlings to defoliation rate.
AB  - Picea mongolica W. D. Xu. is an endemic species in China. The spruce forest is
      only found in semi-arid habitat in Inner Mongolia Autonomous Region of China.
      Based on the simulative defoliation experiment, it was proved that Picea
      mongolica seedlings had the compensatory and overcompensatory effects under the
      certain defoliation rate. The results of variance analysis on growth indexes
      showed that in PM I (natural regeneration seedlings under Picea mongolica
      forest), the differences of H1 (height in June 23) and H2 (height in September 3)
      were extremely significant, and the difference of D(diameter at the breast
      height) were not significant. In PM II (artificial regeneration seedlings under
      Betula platyphylla Suk. forest), the difference of H1 was significant, the
      difference of H2 was not significant, and the difference of D was extremely
      significant. The regression equations were established and the compensatory and
      overcompensatory points were obtained. In PM I, the compensatory points of H1,
      H2, and D were 0.7628, 0.7436, 0.5725, and the overcompensatory points were
      0.6056, 0.5802 and 0.2909 respectively. In PM II, the compensatory points of H,,
      H2, and D are 0.5012, 0.3421, 0.2488, and the overcompensatory points are 0.4137,
      0.2633 and 0.0747 respectively. These results suggested that the induction of
      compensatory growth mechanisms in spruce seedlings required a threshold level of
      defoliation, and the insects in Picea mongolica forest could be controlled in a
      certain degree.

PMID- 16295894
TI  - Seasonal variation of nitrogen-concentration in the surface water and its
      relationship with land use in a catchment of northern China.
AB  - Surface waters can be contaminated by human activities in two ways: (1) by point
      sources, such as sewage treatment discharge and storm-water runoff; and (2) by
      non-point sources, such as runoff from urban and agricultural areas. With point
      source pollution effectively controlled, non-point source pollution has become
      the most important environmental concern in the world. The formation of non-point
      source pollution is related to both the sources such as soil nutrient, the amount
      of fertilizer and pesticide applied, the amount of refuse, and the spatial
      complex combination of land uses within a heterogeneous landscape. Land-use
      change, dominated by human activities, has a significant impact on water
      resources and quality. In this study, fifteen surface water monitoring points in
      the Yuqiao Reservoir Basin, Zunhua, Hebei Province, northern China, were chosen
      to study the seasonal variation of nitrogen concentration in the surface water.
      Water samples were collected in low-flow period (June), high-flow period (July)
      and mean-flow period (October) from 1999 to 2000. The results indicated that the
      seasonal variation of nitrogen concentration in the surface water among the
      fifteen monitoring points in the rainfall-rich year is more complex than that in
      the rainfall-deficit year. It was found that the land use, the characteristics of
      the surface river system, rainfall, and human activities play an important role
      in the seasonal variation of N-concentration in surface water.

PMID- 16295896
TI  - Effects of beta-cyclodextrins on the enzymatical hydrolysis of chiral dichlorprop
      methyl ester.
AB  - The effect of beta-cyclodextrins (beta-CDs) on the enzymatical hydrolysis of
      chiral dichlorprop methyl ester (DCPPM) was studied. Four kinds of beta
      cyclodextrins (beta-cyclodextrin, Partly methylated-CD (PM-beta-CD),
      hydroxypropyl-cyclodextrin (HP-beta-CD) and carboxymethyl-cyclodextrin (CM-beta
      CD)) were used. Compared with 100% DCPPM in the absence of betacyclodextrins, the
      activity of lipase decreased with the increase of Pbetacyclodextrin and PM
      Pbetacyclodextrin. However, CM-beta-clodextrin stimulated the lipase activity.
      The inhibition effect of Pbeta cyclodextrin and PM-5betacyclodextrin on the
      hydrolysis of DCPPM is affected by many factors other than degree of the
      methylation blocking the active site of lipase. UV-Vis and Fourier transform
      infrared (FTIR) spectroscopy studies of the complexation of aqueous DCPPM with
      beta-CDs provide fresh insight into the molecular structure of the complex and
      explain the effects of beta-CDs on enzymatical hydrolysis of chiral DCPPM. Data
      showed that inclusion complexes had formed by complexation of the CM-beta-CD with
      DCPPM and the solubility of DCPPM was increased in water, which lead to the
      increased lipase activity.

PMID- 16295897
TI  - Release of bioactive active iodine in kelp.
AB  - The release process and influencing factors of bioactive iodine of kelp are
      systemically studied by leaching experiment. The results showed that the
      bioactive iodine of kelp can be released rapidly and the principal form of iodine
      in lixivium is I-. There is a dynamic process between the release and absorption
      of iodine. With the increase of leaching water, the gross amounts of released
      iodine rise. There also exists a transforming process among I-, IO3- and organic
      iodine in lixivium.

PMID- 16295898
TI  - Control of diesel soot and NOx emissions with a particulate trap and EGR.
AB  - The exhaust gas recirculation (EGR), coupled with a high-collection efficiency
      particulate trap to simultaneously control smoke and NOx emissions from diesel
      engines were studied. This ceramic trap developed previously provided the soot
      cleaning efficiency of 99%, the regeneration efficiency reaches 80% and the ratio
      of success reaches 97%, which make EGR used in diesel possible. At the presence
      of EGR, opening of the regeneration control valve of the trap was over again
      optimized to compensate for the decrease of the oxygen concentration in the
      exhaust gas resulted from EGR. The results indicated the cleaning efficiency and
      regeneration performance of the trap were maintained at the same level except
      that the back pressure increased faster. A new EGR system was developed, which is
      based on a wide range oxygen (UEGO) sensor. Experiments were carried out under
      steady state conditions while maintaining the engine speed at 1600 r/min, setting
      the engine loads at 0%, 25%, 50%, 75% and 100% respectively. Throughout each test
      the EGR rate was kept at nine different settings and data were taken with the gas
      analyzer and UEGO sensor. Then, the EGR rate and engine load maps, which showed
      the tendencies of NOx, CO and HC emissions from diesel engine, were made using
      the measured data. Using the maps, the author set up the EGR regulation, the
      relationship between the optimal amounts of EGR flow and the equivalence ratio,
      sigma, where sigma = 14.5/AFR.

PMID- 16295899
TI  - Anaerobic digestion of kitchen wastes in a single-phased anaerobic sequencing
      batch reactor (ASBR) with gas-phased absorb of CO2.
AB  - The performance of the single-stage anaerobic digestion of kitchen wastes was
      investigated in an anaerobic sequencing batch reactor(ASBR) with gas-phased
      absorb of CO2. The ASBR was operated at four chemical oxygen demand(COD) loading
      rates, 2.8, 5.1, 6.2 and 8.4 g/(L x d) respectively. The COD loading rate was
      increased with the TS concentration and HRT changing. At maximum COD loading rate
      of 8.4 g/(L x d), the COD, total solid(TS) removal rate and methane gas yield
      were 69%, 68% and 2.5 L/(L x d) respectively. The operation of the reactor with
      gas-phased absorb of CO2 was stable in spite of the low pH (2.6-3.9) and high
      concentration of TS (142 g/L) of input mixture. The output volatile fatty
      acid(VFA) concentration was between 2.7-4.7 g/L and had no inhibition on the
      methanogenic microorganism. The reactor without gas-phased absorb of CO2 became
      acidified when the total COD loading rate was increased to 5.1 g/(L x d).
      Stoichiometry of the methanogenesis for kitchen wastes showed a considerable
      amount of alkaline will be required to keep pH in the appropriate range for the
      methanogenic microorganism based on theoretical calculation. Gas-phased absorb of
      CO2 effectively reduced the alkaline consumption, hence avoided excessive cation
      into the reactor.

PMID- 16295900
TI  - Neurotransmitter level changes in domestic ducks (Shaoxing duck) growing up in
      typical mercury contaminated area in China.
AB  - The neurotransmitter level changes of ducks exposed 8-month in a mercury-polluted
      site (Wanshan, China) and a reference site (Shanghai, China) were examined.
      Chemical analyses showed both higher mercury and selenium concentrations in the
      organ of Wanshan ducks. An increased content of acetylcholine (ACh) in brain and
      blood and a decreased activity of acetylcholinesterase (AChE) in blood were
      observed. Moreover, there was an increasing trend for nitric oxide synthase (NOS)
      activity and nitric oxide(NO) production in duck brain, but a reduction of NOS
      activity in duck serum. The possible explanations were due to the interactive
      effect of selenium accumulation and the sublethal exposure level of mercury in
      Wanshan area. The present study showed that AChE and NOS were sensitive to
      mercury contamination of real circumstance, suggesting that these two indexes
      have the potential to be biomarkers in assessment of health effects by mercury
      contamination.

PMID- 16295901
TI  - Effects of salinity on activities of H+ -ATPase, H+ -PPase and membrane lipid
      composition in plasma membrane and tonoplast vesicles isolated from soybean
      (Glycine max L.) seedlings.
AB  - The effects of NaCl stress on the H+ -ATPase, H+ -PPase activity and lipid
      composition of plasma membrane (PM) and tonoplast(TP) vesicles isolated from
      roots and leaves of two soybean cultivars (Glycine max L.) differing in salt
      tolerance (Wenfeng7, salt-tolerant; Union, salt-sensitive) were investigated.
      When Wenfeng7 was treated with 0.3% (W/V) NaCl for 3 d, the H+ -ATPase activities
      in PM and TP from roots and leaves exhibited a reduction and an enhancement,
      respectively. The H+ -PPase activity in TP from roots also increased. Similar
      effects were not observed in roots of Union. In addition, the increases of
      phospholipid content and ratios of phospholipid to galactolipid in PM and TP from
      roots and leaves of Wenfeng7 may also change membrane permeability and hence
      affect salt tolerance.

PMID- 16295902
TI  - Risk forecasting and evaluating model of environmental pollution accident.
AB  - Environmental risk (ER) factors come from ER source and they are controlled by
      the primary control mechanism (PCM) of environmental risk, due to the self
      failures or the effects of external environment risk trigger mechanism, the PCM
      could not work regularly any more, then, the ER factors will release
      environmental space, and an ER field is formed up. The forming of ER field does
      not mean that any environmental pollution accident (EPA) will break out; only the
      ER receptors are exposed in the ER field and damaged seriously, the potential ER
      really turns into an actual EPA. Researching on the general laws of evolving from
      environmental risk to EPA, this paper bring forwards a relevant concept model of
      risk forecasting and evaluating of EPA. This model provides some scientific
      methods for risk evaluation, prevention and emergency response of EPA. This model
      not only enriches and develops the theory system of environment safety and
      emergency response, but also acts as an instruction for public safety,
      enterprise' s safety management and emergency response of the accident.

PMID- 16295903
TI  - Cultivation of aerobic granules for simultaneous nitrification and
      denitrification by seeding different inoculated sludge.
AB  - Cultivation of aerobic granules for simultaneous nitrification and
      denitrification in two sequencing batch airlift bioreactors was studied.
      Conventional activated floc and anaerobic granules served as main two inoculated
      sludge in the systems. Morphological variations of sludge in the reactors were
      observed. It was found that the cultivation of aerobic granules was closely
      associated with the kind of inoculated sludge. Round and regular aerobic granules
      were prevailed in both reactors, and the physical characteristics of the aerobic
      granules in terms of settling ability, specific gravity, and ratio of water
      containing were distinct when the inoculate sludge was different. Aerobic
      granules formed by seeding activated floc are more excellent in simultaneous
      nitrification and denitrification than that by aerobic granules formed from
      anaerobic granules. It was concluded that inoculated sludge plays a crucial role
      in the cultivation of aerobic granules for simultaneous nitrification and
      denitrification.

PMID- 16295904
TI  - Degradation of 2,6-di-tert-butylphenol by an isolated high-efficiency bacterium
      strain.
AB  - An aerobic bacterium strain, F-3-4, capable of effectively degrading 2, 6-ditert
      butylphenol (2, 6-DTBP), was isolated and screened out from an acrylic fiber
      wastewater and the biofilm in the wastewater treatment facilities. This strain
      was identified as Alcaligenes sp. through morphological, physiological and
      biochemical examinations. After cultivation, the strain was enhanced by 26.3% in
      its degradation capacity for 2,6-DTBP. Results indicated that the strain was able
      to utilize 2,6-DTBP, lysine, lactamine, citrate, n-utenedioic acid and malic acid
      as the sole carbon and energy source, alkalinize acetamide, asparagine, L
      histidine, acetate, citrate and propionate, but failed to utilize glucose, D
      fructose, D-seminose, D-xylose, serine and phenylalanine as the sole carbon and
      energy source. The optimal growth conditions were determined to be: temperature
      37 degrees C, pH 7.0, inoculum size 0.1% and shaker rotary speed 250 r/min. Under
      the optimal conditions, the degradation kinetics of 2,6-DTBP with an initial
      concentration of 100 mg/L was studied. Results indicated that 62.4% of 2,6-DTBP
      was removed after 11 d. The degradation kinetics could be expressed by
      Eckenfelder equation with a half life of 9.38 d. In addition, the initial
      concentration of 2,6-DTBP played an important role on the degradation ability of
      the strain. The maximum initial concentration of 2,6-DTBP was determined to be
      200 mg/L. Above this level, the strain was overloaded and exhibited significant
      inhibition.

PMID- 16295905
TI  - The role of arbuscular mycorrhiza on change of heavy metal speciation in
      rhizosphere of maize in wastewater irrigated agriculture soil.
AB  - To understand the roles of mycorrhiza in metal speciation in the rhizosphere and
      the impact on increasing host plant tolerance against excessive heavy metals in
      soil, maize (Zea mays L.) inoculated with arbuscular mycorrhizal fungus (Glomus
      mosseae) was cultivated in heavy metal contaminated soil. Speciations of copper,
      zinc and lead in the soil were analyzed with the technique of sequential
      extraction. The results showed that, in comparison to the bolked soil, the
      exchangeable copper increased from 26% to 43% in non-infected and AM-infected
      rhizoshpere respectively; while other speciation (organic, carbonate and Fe-Mn
      oxide copper) remained constant and the organic bound zinc and lead also
      increased but the exchangeable zinc and lead were undetectable. The organic bound
      copper, zinc and lead were higher by 15%, 40% and 20%, respectively, in the
      rhizosphere of arbuscular mycorrhiza infected maize in comparison to the non
      infected maize. The results might indicate that mycorrhiza could protect its host
      plants from the phytotoxicity of excessive copper, zinc and lead by changing the
      speciation from bio-available to the non-bio-available form. The fact that copper
      and zinc accumulation in the roots and shoots of mycorrhia infected plants were
      significantly lower than those in the non-infected plants might also suggest that
      mycorrhiza efficiently restricted excessive copper and zinc absorptions into the
      host plants. Compared to the non-infected seedlings, the lead content of infected
      seedlings was 60% higher in shoots. This might illustrate that mycorrhiza have a
      different mechanism for protecting its host from excessive lead phytotoxicity by
      chelating lead in the shoots.

PMID- 16295906
TI  - Effect of media heights on the performance of biological aerated filter.
AB  - The optimum media height of carbon oxidation and nitrification in a down-flow
      biological aerated filter was determined, and the distribution of the
      heterotrophic and nitrifying populations through studying the changes of organic
      carbon contents and ammonia concentration at different media height was got. The
      results showed that as a down flow BAF with granular media, the active layer of
      nitrifiers was deeper than heterotrophs in BAF. And the optimum media height for
      the removal of SS, COD(Cr) and NH4+ -N was 40 cm, 60 cm and 80 cm respectively.
      The removal efficiency of SS, COD(Cr), and NH4+ -N was 79.1%, 63.9% and 96.4%
      respectively under the influent COD(Cr), and NH4+ -N of 122.1 mgCOD(Cr)/L and
      14.84 mgNH4+ -N/L, the influent flux of 15.8 L/h, air to liquid ratio of 3:1.

PMID- 16295907
TI  - Bioconcentration of polycyclic aromatic hydrocarbons in roots of three mangrove
      species in Jiulong River Estuary.
AB  - The polycyclic aromatic hydrocarbons(PAHs) concentrations were determined in the
      root of three mangrove species (Kandelia candel, Avicennia marina and Bruguiera
      gymnorrhiza) and their growing environment (sediment) in mangrove wetlands of
      Jiulong River Estuary, Fujian, China. The total PAHs (16 parent PAHs) in mangrove
      sediments ranged from 193.44 to 270.53 ng/g dw, with a mean value of 231.76 +/-
      31.78 ng/g dw. Compared with other mangrove and coastal marine sediments, the
      PAHs concentrations of all the sampling areas in this study were at relatively
      lower level. The total PAHs (13 parent PAHs) values varied from 30.83 to 62.73
      ng/g dw in mangrove roots. Benzo[a]pyrene(five-ring), fluoranthene(four-ring) and
      pyrene(four-ring) dominated in mangrove sediments. Based on ratios of
      phenathrene/anthracene, fluoranthene/pyrene and fluoranthene/pyrene +
      fluoranthene, the main possible sources of surface sediment PAHs were identified
      as grass, wood or coal combustion for mangrove wetlands of Jiulong River Estuary.
      Naphthalene(two-ring) and phenathrene(three-ring) were the most abundant
      compounds in mangrove roots. Sediment-to-vegetation bioconcentration factors
      (BCF(SV) S) were calculated and their relationships with PAHs' physico-chemical
      properties were investigated. The average BCF(SV) S of PAHs for three mangrove
      species roots were almost all under the level of 1 except for naphthalene. Good
      linear relationship between BCF(SV) values for mangrove roots and PAHs water
      solubility, octanol-water partitioning coefficients was derived in present study.
      The solubility and the octanol-water partition coefficient were proved to be good
      predictors for the accumulation of PAHs in mangrove roots, respectively.

PMID- 16295908
TI  - Enhanced photocatalytic activity of nanotube-like titania by sulfuric acid
      treatment.
AB  - The TiO2 nanotube sample was prepared via a NaOH solution in a Teflon vessel at
      150 degrees C. The as-prepared nanotubes were then treated with H2 SO4 solutions.
      The TiO2 nanotube has a crystalline structure with open-ended and multiwall
      morphologies. The TiO2 nanotubes before and after surface acid treatment were
      characterized by X-ray diffraction (XRD), scanning electron microscopy(SEM),
      transmission electron microscopy (TEM) and UV-VIS dispersive energy
      spectrophotometry (DRS). The photocatalytic activity of the samples was evaluated
      by photocatalytic degradation of acid orange II in aqueous solutions. It was
      found that the order of photocatalytic activity was as follows: TiO2 nanotubes
      treated with 1.0 mol/L H2SO4 solution (TiO2 (1.0M H2SO4) snanotubes) > TiO2
      nanotubes treated with 0.2 mol/L H2SO4 solution (TiO2 (0.2M H2O4) nanotubes) >
      TiO2 nanotubes > TiO2 powder. This was attributed to the fact that TiO2 nanotubes
      treated with H2SO4 was composed of smaller particles and had higher specific
      surface areas. Furthermore, the smaller TiO2 particles were beneficial to the
      transfer and separation of photo-generated electrons and holes in the inner of
      and on the surface of TiO2 particles and reduced the recombination of photo
      generated electrons and holes. Acid treatment was particularly effective for TiO2
      nanotubes, this increase in activity was correlated with the concentration of H2
      SO4 solution.

PMID- 16295909
TI  - Metal bioaccumulation in plant leaves from an industrious area and the botanical
      garden in Beijing.
AB  - The concentrations of Fe, Mn, Al, Zn, Pb, Ni, Cr, and As were measured in soils
      and leaves from 21 plant species growing on hills near the Beijing Steel Factory
      (BSF) and 17 plant species in the Beijing Botanical Garden (BBG). The results
      showed that soils from BSF were Zn contaminated according to the threshold of
      natural background of China. There was a metal contamination of the soils by Ni,
      and Cr in BSF comparing with those in BBG. The comparison between concentrations
      of metals in leaves from both sites indicated that, in general, accumulation of
      metals in the leaves of the same species was significantly different between the
      two sites. Even within the same locality each species accumulation of metals was
      significantly variable. The study aimed to screen landscape plants for the
      capacity to clean-up toxic metals in soils, and developed an overall metal
      accumulation index (MAI) for leaves and then categorized the MAI that can be
      applied broadly in the selection of species in polluted areas. To do this, the
      spectrum of MAI values were divided into four classes: strongly accumulated (SA
      or grade I), moderately accumulated (MA or grade II), intermediately accumulated
      (IA or grade III), and weakly accumulated (WA or grade IV). The results showed
      that elemental association between Fe, Al, Ni, and As was generally highly
      correlated with each other in the sampling sites. This may suggest their common
      biochemical characteristics. Generally, those species containing strong and
      moderate accumulation in both sites are considered including Vitex negundo,
      Broussonetia papyrifera, Ulmus pumila, and Rubia cordifolia. At BSF and other
      industrial sites with a similar ecosystem, strong and moderate accumulation
      species include Sophora japonica, Ampelopsis aconitifolia var. glabra,
      Platycladus orientalis, Wikstroemia chamaedaphne, Cleistogenes squarrosa, Grewia
      biloba, and in BBG, in addition Setaria viridis, Cotinus coggygria, Lespedeza
      floribunda, Rhamnus parvifolia, Lespedeza tomentosa.

PMID- 16295910
TI  - Effect of electron beam irradiation on the degradation of monochlorophenols in
      aqueous solution.
AB  - Electron beam was successfully used for the degradation of 2-chlorophenol (2-CP)
      and 4-chlorophenol (4-CP) in aqueous solutions in this research. The effect of
      radiation dose on substrate degradation and dechlorination of solutions with
      concentration of 50 mg/L was investigated. The effect of initial concentration,
      pH and presence of oxygen was also investigated. The concentration of 2-CP and 4
      CP remaining in solution after irradiation were measured by HPLC. The results
      showed that increased radiation dose led to increased degradation of the
      chlorophenols and increased Cl- yield. Deaeration was also found to significantly
      increase the rate of degradation of chlorophenols in water while degradation and
      dechlorination under alkaline condition was lower than at low to neutral pH.

PMID- 16295911
TI  - Simulation on an optimal combustion control strategy for 3-D temperature
      distributions in tangentially pc-fired utility boiler furnaces.
AB  - The control of 3-D temperature distribution in a utility boiler furnace is
      essential for the safe, economic and clean operation of pc-fired furnace with
      multi-burner system. The development of the visualization of 3-D temperature
      distributions in pc-fired furnaces makes it possible for a new combustion control
      strategy directly with the furnace temperature as its goal to improve the control
      quality for the combustion processes. Studied in this paper is such a new
      strategy that the whole furnace is divided into several parts in the vertical
      direction, and the average temperature and its bias from the center in every
      cross section can be extracted from the visualization results of the 3-D
      temperature distributions. In the simulation stage, a computational fluid
      dynamics (CFD) code served to calculate the 3-D temperature distributions in a
      furnace, then a linear model was set up to relate the features of the temperature
      distributions with the input of the combustion processes, such as the flow rates
      of fuel and air fed into the furnaces through all the burners. The adaptive
      genetic algorithm was adopted to find the optimal combination of the whole input
      parameters which ensure to form an optimal 3-D temperature field in the furnace
      desired for the operation of boiler. Simulation results showed that the strategy
      could soon find the factors making the temperature distribution apart from the
      optimal state and give correct adjusting suggestions.

PMID- 16295912
TI  - Persistent organic pollutants control strategy in China.
AB  - The development of Persistent Organic Pollutants (POPs) control policy in China
      in the context of international concerns on POPs was reviewed. The aspects of the
      Chinese POPs control strategies were analyzed, and compared with those of
      developed counterparts (e.g. U.S., E.U., Japan). Currently, while the legal
      framework on POPs management, which complies with international guidelines has
      been established, it should be improved in the areas of special POPs management,
      risk assessment, the precautionary principle, life-cycle management and technical
      support capacity. The analysis of Chinese POPs policy and suggestions for
      strengthening the science-based decision making capacity are not only useful for
      Chinese decision-makers, but also a case study for developing world and make a
      great contribution for the global elimination of POPs to make a toxic-free
      future.

PMID- 16295913
TI  - Removal of disinfection by-products formation potential by biologically
      intensified process.
AB  - The removal of disinfection by-products formation potential (DBPFP) in
      artificially intensified biological activated carbon (IBAC) process which is
      developed on the basis of traditional ozone granular activated carbon was
      evaluated. By IBAC removals of 31% and 68% for THMFP and HAAFP were obtained
      respectively. Under identical conditions, the removals of the same substances
      were 4% and 32% respectively only by the granular activated carbon (GAC) process.
      Compared with GAC, the high removal rates of the two formed potential substances
      were due to the increasing of bioactivity of the media and the synergistic
      capabilities of biological degradation cooperating with lactivated carbon
      adsorption of organic compounds. A clear linear correlation (R2 = 0.9562 and R2 =
      0.9007) between DOC HAAFP removal rate and Empty Bed Contact Time (EBCT) of IBAC
      process was observed, while that between THMFP removal rate and EBCT of GAC was
      R2 = 0.9782. In addition certain linear correlations between THMFP, HAAFP and
      UV254 (R2 = 0.855 and R2 = 0.7702) were found for the treated water. For IBAC
      process there are also more advantages such as long backwashing cycle time, low
      backwashing intensity and prolonging activated carbon lifetime and so on.

PMID- 16295914
TI  - Real-world vehicle emission factors in Chinese metropolis city--Beijing.
AB  - The dynamometer tests with different driving cycles and the real-world tests are
      presented. Results indicated the pollutants emission factors and fuel consumption
      factor with ECE15 + EUDC driving cycle usually take the lowest value and with
      real world driving cycle occur the highest value, and different driving cycles
      will lead to significantly different vehicle emission factors with the same
      vehicle. Relative to the ECE15 + EUDC driving cycle, the increasing rate of
      pollutant emission factors of CO, NOx and HC are - 0.42-2.99, -0.32-0.81 and 
      0.11-11 with FTP75 testing, 0.11-1.29, -0.77-0.64 and 0.47-10.50 with Beijing
      1997 testing and 0.25-1.83, 0.09-0.75 and - 0.58-1.50 with real world testing.
      Compared to the carburetor vehicles, the retrofit and MPI + TWC vehicles'
      pollution emissionfactors decrease with different degree. The retrofit vehicle
      (Santana) will reduce 4.44%-58.44% CO, -4.95%-36.79% NOx, -32.32%-33.89% HC, and 
      9.39%-14.29% fuel consumption, and especially that the MPI + TWC vehicle will
      decrease CO by 82.48%-91.76%, NOx by 44.87%-92.79%, HC by 90.00%-93.89% and fuel
      consumption by 5.44%-10.55%. Vehicles can cause pollution at a very high rate
      when operated in high power modes; however, they may not often operate in these
      high power modes. In analyzing vehicle emissions, it describes the fraction of
      time that vehicles operate in various power modes. In Beijing, vehicles spend 90%
      of their operation in low power modes or decelerating.

PMID- 16295915
TI  - Eco-environment contribution of agroforestry to agriculture development in the
      plain area of China--Huai' an Prefecture, Jiangsu Province as the case study
      area.
AB  - For improving the environmental quality and ensuring supply of wood and non
      timber forest products, many forests have been planted in plain areas of China.
      Scientists have studied their benefits, almost all of the approaches were based
      on fixed-point data, and few was considered on the non-efficient factors and
      temporal scale effects. This paper studies the positive and negative benefits at
      a large temporal scale, and the effects of plain afforestation on stockbreeding
      and rural economy. The benefits of plain afforestation, correlation coefficiency
      of agroforestry and production factors are analyzed via stochastic frontier
      modeling in Huanghuaihai Plain Area of China; elastic coefficient of
      agroforestry, husbandry, farming, and total output of agricultural sector are
      calculated through adopting partial differential equation. Some conclusions can
      be drawn that, plain forests have an important effect on the development of plain
      agriculture. But shelterbelts and small-scale forests have different effect on
      the development of agricultural economy. Shelterbelts have negative effect on the
      industries, but small-scale forest has positive effect. On the whole,
      contribution of forest resource to value of animal husbandry and gross production
      value of agriculture is positive, and to the value of farming is negative.

PMID- 16295916
TI  - Mobility and speciation of Cd, Cu, and Zn in two acidic soils affected by
      simulated acid rain.
AB  - Through a batch experiment, the mobility and speciation of heavy metals (Cd, Cu,
      Zn) in two acidic forest soils from Hunan Province were studied. The results
      showed that the release and potential active speciation of Cd, Cu, and Zn in the
      tested contaminated red soil (CRS) and yellow red soil (CYRS) increased
      significantly with pH decreasing and ion concentrations increasing of simulated
      acid rain, and these effects were mainly decided by the pH value of simulated
      acid rain. Cd had the highest potential risk on the environment compared with Cu
      and Zn. Cd existed mainly in exchangeable form in residual CRS and CYRS, Cu in
      organically bound and Mn-oxide occluded forms, and Zn in mineral forms due to the
      high background values.

PMID- 16295917
TI  - Agglomeration rate and action forces between atomized particles of agglomerator
      and inhaled-particles from coal combustion.
AB  - In order to remove efficiently haled-particles emissions from coal combustions, a
      new way was used to put forward the process of agglomeration and the atomization
      was produced by the nozzle and then sprayed into the flue before precipitation
      devices of power station boiler in order to make inhaled-particles agglomerate
      into bigger particles, which can be easily removed but not change existing
      running conditions of boiler. According to this idea, a model is set up to study
      agglomeration rate and effect forces between fly ash inhaled-particles and
      atomized agglomerator particles. The developed agglomeration rate was expressed
      by relative particle number decreasing speed per unit volume. The result showed
      that viscosity force and flow resistance force give main influences on
      agglomeration effect of inhaled-particles, while springiness force and gravity
      have little effect on agglomeration effect of theirs. Factors influencing the
      agglomeration rate and effect forces are studied, including agglomerator
      concentration, agglomerator flux and agglomerator density, atomized-particles
      diameters and inhaled-particles diameter and so on.

PMID- 16295918
TI  - Nitrogen transformation in maize soil after application of different organic
      manures.
AB  - The nitrogen transformation in maize soil after application of different organic
      manure was studied. The nitrogen mineralization in surface soil, NO3- -N dynamics
      and distribution in soil profile, and N2O emission were investigated. Eight
      treatments were laid out randomizing with three replications in 24 plots: maize
      plantation without fertilizer (CK1), bare soil without maize plantation and
      fertilization (CK2), swine manure (S1, S2), poultry manure (P1, P2), and cattle
      manure (C1, C2). Three manures were applied at two application levels (15 t/hm2
      and 30 t/hm2). The results indicated that NH+ -N in surface soil showed the same
      temporal pattern without much variation among different treatments. But NO3- -N
      in the same layer exhibited large temporal pattern in all treatments, which was
      mainly due to its easy eluviations of NO3- -N in soil, its transformation to N2O
      and the influence of precipitation. The distribution of NO3- -N in the soil
      profile during maize growing season showed the leaching tendency from surface
      soil to subsoil, which was different among the treatments. The poultry treatments
      showed the largest leaching tendency. The study also revealed that the emissions
      of N2O were affected by the application of organic manures in the order of P2 >
      S2 > C2 > P1 > S1 > Cl > CK1 > CK2. All these results showed that organic manure
      applications significantly affect nitrogen transformation and distribution in
      maize soil. Considering N2O emission and NO3- -N leaching, the management of
      organic manure in the agriculture needs further studies.

PMID- 16295919
TI  - Relationship between urban eco-environment and competitiveness with the
      background of globalization: statistical explanation based on industry type newly
      classified with environment demand and environment pressure.
AB  - Within the global urban system, the statistical relationship between urban eco
      environment (UE) and urban competitiveness (UC) (RUEC) is researched. Data showed
      that there is a statistically inverted-U relationship between UE and UC. Eco
      environmental factor is put into the classification of industries, and gets six
      industrial types by two indexes viz. industries' eco-environmental demand and
      pressure. The statistical results showed that there is a strong relationship, for
      new industrial classification, between the changes of industrial structure and
      evolvement of UE. The drive mechanism of the evolvement of urban eco-environment,
      with human demand and global work division was analyzed. The conclusion is that
      the development stratege, industrial policies of cities, and environmental
      policies fo cities must be fit with their ranks among the global urban system. At
      the era of globalization, so far as the environmental policies, their rationality
      could not be assessed with the level of strictness, but it can enhance cities'
      competitiveness when they are fit with cities' capabilities to attract and
      control some sections of the industry's value-chain. None but these kinds of
      environmental policies can probably enhance the UC.

PMID- 16295920
TI  - Preparation of TiO2-MoO3 nano-composite photo-catalyst by supercritical fluid dry
      method.
AB  - A series of TiO2-MoO3 nano-composite photocatalysts were prepared by
      supercritical fluid dry method (SCFD) and an impregnation technique with TiCl4
      and (NH4)6Mo7O24.4H2O as the starting materials. The catalysts were characterized
      by the means of XRD, TEM and UV-Vis. Methyl orange was used as model compound for
      the evaluation of their catalytic activities. The results indicated that the
      photo-catalyst prepared by SCFD had the advantages of small size (12.84 nm),
      narrow distribution and good dispersivity. The presence of small amount of Mo in
      composite catalyst gives rise to the red shift of its absorbance wavelength,
      decrease of its energy gap and increase of the utility of visible light.
      Furthermore, higher surface acidity of the photo-catalyst was obtained as the
      result of the addition of MoO3. Compared with pure TiO2, the catalytic activity
      of the TiO2-MoO3 nano-composite photo-catalyst was improved significantly. As the
      doping concentration of the composite catalysts was controlled at 0.6% (molar
      percentage), 100% degradation of methyl orange was achieved with in 1.2 h
      irradiation time.

PMID- 16295921
TI  - Iceland's plan for genomics research: facts and implications.
AB  - The government of Iceland has authorized a private, for-profit firm, deCODE
      Genetics, to construct a database of the population's medical records as part of
      a larger plan by deCODE for human genetics research. This article presents the
      background for genetics research in Iceland, the history of deCODE, and the terms
      of the law authorizing the database. It then examines five objections to the law,
      based on commercialization, lack of informed consent, risks to privacy, the
      effects of other research, and financial unfairness. It concludes that the
      Icelandic model is not a good precedent for similar research elsewhere.

PMID- 16295922
TI  - MRSA: an emerging equine problem?

PMID- 16295923
TI  - Closing in on the equine joint.

PMID- 16295924
TI  - Two clinical manifestations of desmopathy of the accessory ligament of the deep
      digital flexor tendon in the hindlimb of 23 horses.
AB  - REASONS FOR PERFORMING STUDY: Desmopathy of the accessory ligament of the deep
      digital flexor tendon (ALDDFT) in the hindlimb is an unusual cause of lameness in
      horses, and reports of the condition are sparse. OBJECTIVES: To describe the
      clinical and ultrasonographic findings, therapy and outcome of 23 horses treated
      for desmopathy of the ALDDFT in the hindlimb. METHODS: Records of 23 horses with
      ultrasonographic evidence of desmopathy of the ALDDFT in one or both hindlimbs
      from 3 referral centres were reviewed retrospectively. Age, breed, sex, duration
      and nature of clinical signs, results of clinical and lameness examinations,
      treatment and outcome were recorded. RESULTS: In 13 horses (Group A), there was
      an acute onset of unilateral lameness. Ten horses (Group B) had an insidious or
      sudden onset of postural abnormality. There were 10 cobs, 5 British native-breed
      ponies and 8 horses of various larger breeds. Twenty horses were used for general
      purposes, and mean age was 12 years. Enlargement of the ALDDFT in the affected
      hindlimb(s) was identified in all horses. In 44% of horses, ultrasonographic
      abnormalities were localised to part of the ALDDFT. Treatment included box-rest
      and controlled exercise, and 10 horses were subjected to desmotomy or desmectomy
      of the ALDDFT. Seventy-three percent of horses in Group A returned to full
      function, while 90% of those in Group B remained lame. CONCLUSIONS: Two distinct
      clinical conditions are associated with the ALDDFT of the hindlimb. Traumatically
      induced injury resulting in acute onset lameness appears to have a favourable
      prognosis, with most horses returning to previous work. However, postural
      changes, once present, are irreversible and indicate a poor prognosis. POTENTIAL
      RELEVANCE: Desmopathy of the ALDDFT should be recognised as a potential cause of
      hindlimb lameness and this study provides clinical and prognostic information.
      Knuckling and/or semiflexion of the metatarsophalangeal joint may accompany the
      condition; therefore, if a horse is presented with a flexural deformity of this
      joint, desmopathy of the ALDDFT should be considered as a primary differential
      diagnosis.

PMID- 16295925
TI  - Effect of repeated oral administration of hypertonic electrolyte solution on
      equine gastric mucosa.
AB  - REASONS FOR PERFORMING STUDY: Electrolyte supplementation is common in horses
      during endurance competitions, but the effect on the gastric mucosa is unknown.
      HYPOTHESIS: Repeated oral administration of hypertonic electrolyte solution is
      associated with exacerbation of gastric ulcers in mature horses. METHODS: The
      study design was a randomised, blinded, crossover trial. Fourteen horses were
      divided randomly into equal groups and administered either 60 ml water (placebo)
      or 56.7 g commercial electrolyte supplement mixed with 60 ml water by dose
      syringe orally once an hour for 8 h. The minimum concentration of individual
      constituent electrolytes/28.35 g dry commercial product used was: sodium (5528
      mg); chloride (11,886 mg); potassium (3657 mg); calcium (754 mg); and magnesium
      (153 mg). Gastric lesions were scored prior to and after oral treatments, and
      analysis of variance procedures were then performed. RESULTS: Administration of
      hypertonic electrolytes resulted in a significant increase in mean ulcer number
      (P = 0.0174) and severity (P = 0.0006) scores in the nonglandular stomach. Mean
      ulcer number score was 3.6 and mean ulcer severity score 2.7 after hypertonic
      electrolyte treatment. CONCLUSIONS: Oral hypertonic electrolyte administration to
      horses in this model was associated with exacerbation of gastric ulcers.
      POTENTIAL RELEVANCE: Our findings suggest that one schedule of electrolyte
      supplementation used commonly in endurance horses may be harmful to the gastric
      mucosa.

PMID- 16295926
TI  - Supernumerary cheek teeth (n = 24): clinical features, diagnosis, treatment and
      outcome in 15 horses.
AB  - REASONS FOR PERFORMING STUDY: There are few reports of case series of horses with
      supernumerary cheek teeth (SCT) that document clinical findings, treatment and
      long-term outcome. OBJECTIVES: To review the clinical and ancillary diagnostic
      findings and responses to different treatments in horses with SCT. METHODS: The
      case records of 15 horses were reviewed and long-term outcomes obtained by
      telephone interview. RESULTS: Fifteen horses with a total of 24 SCT were
      identified. Two SCT were incidental findings and were not treated. Clinical signs
      were improved or resolved in 11 of 13 of the teeth treated conservatively and all
      6 treated by extraction had a favourable outcome. Four horses were subjected to
      euthanasia within a short period of diagnosis, either due to a poor prognosis at
      the outset or failure to respond to initial conservative treatment. CONCLUSIONS:
      Some SCT are chance findings and do not cause clinical signs. In those instances
      where clinical signs of dental disease are mild, conservative treatment including
      the management of diastema and reduction of overgrowths is often effective.
      Horses with severe clinical signs attributable to an SCT are likely to require
      extraction of the offending tooth. POTENTIAL RELEVANCE: An SCT is an uncommon
      dental anomaly but should be considered in the differential diagnosis of cases
      with signs of severe dental disease. The preferred management for SCT is very
      variable and determined by the severity of the associated changes, but ranges
      from conservative measures through forceps extraction per os to major facial flap
      surgery.

PMID- 16295928
TI  - Effect of seminal plasma on uterine inflammation, contractility and pregnancy
      rates in mares.
AB  - REASONS FOR PERFORMING STUDY: There is conflicting evidence over the role seminal
      plasma plays in sperm transport and inflammation within the uterus of mares. In
      in vitro studies, seminal plasma has been shown to reduce polymorphonuclear
      neutrophil (PMN) function, but the opposite effect on uterine inflammation has
      been reported in vivo. OBJECTIVES: To study the effect of seminal plasma on
      uterine contractility, inflammation and pregnancy rates by inseminating mares
      with low doses of sperm free from seminal plasma (Group 1) and containing seminal
      plasma (Group 2). METHODS: Synchronised mares were inseminated with 50 x 10(6)
      sperm in either skim milk extender or seminal plasma. Uterine lavage was
      performed 6 h after insemination to assess the inflammatory response. The
      contraction frequency of the uterus was measured over a 4 min period 10 mins and
      6 h after insemination, using B-mode ultrasonography. Pregnancy rates were
      assessed 16 days after insemination. RESULTS: Uterine contractions were less
      frequent in Group 1 mares inseminated with seminal plasma and significantly more
      PMNs were found in the lavage fluid of those mares. Pregnancy rates were
      identical in both groups (62%). CONCLUSIONS: This study provides evidence that
      seminal plasma decreases uterine contractility and increases the inflammatory
      response of the uterus to semen. No effect of seminal plasma on pregnancy rates
      was demonstrated. POTENTIAL RELEVANCE: Mares that develop persistent mating
      induced endometritis may have inherently poor uterine contractility and impaired
      uterine clearance. The presence of seminal plasma during breeding may not be
      desirable in these mares. The role of seminal plasma in problem mares warrants
      additional study.

PMID- 16295927
TI  - Attempted eradication of methicillin-resistant staphylococcus aureus colonisation
      in horses on two farms.
AB  - REASONS FOR PERFORMING STUDY: Methicillin-resistant Staphylococcus aureus (MRSA)
      is an emerging equine and zoonotic pathogen. Infection control protocols can be
      used to control MRSA in human hospitals, but measures to eradicate MRSA on horse
      farms have not been evaluated. OBJECTIVES: To describe an MRSA eradication
      programme that was used to attempt to eliminate MRSA colonisation among horses
      and horse personnel on 2 equine farms. METHODS: Active surveillance cultures and
      infection control protocols were implemented on 2 farms with endemic MRSA.
      RESULTS: Active screening and strict implementation of infection control
      protocols resulted in a rapid decrease in number of colonised horses on both
      farms. The majority of horses eliminated MRSA without antimicrobial treatment. On
      one farm colonisation was eradicated, while only 2 (3%) colonised horses remained
      on the other farm at the end of the study. CONCLUSIONS: Although at this stage
      the benefit of eradication of MRSA from populations of horses and cost-benefit
      studies have not been established, this study illustrates that short-term
      eradication can be achieved with a policy of segregation, enhanced infection
      control precautions and repeated testing of groups of animals. POTENTIAL
      RELEVANCE: Infection control practices should form the basis of MRSA control.
      Antimicrobial therapy does not appear to be required for eradication of MRSA
      colonisation in horses and control of MRSA on farms. In appropriate
      circumstances, these methods may be useful for controlling the spread of this
      potentially serious pathogen.

PMID- 16295930
TI  - Radiographic anatomy of the soft tissue attachments of the equine stifle.
AB  - REASONS FOR PERFORMING STUDY: Radiography is a very important aspect of equine
      stifle imaging. The precise radiographic anatomy of the soft tissue structures of
      the equine stifle has not been described previously. OBJECTIVE: To describe the
      anatomical relationship between sites of attachment of soft tissue structures of
      the equine stifle and their locations on standard radiographic views. METHODS:
      The sites of bony attachments of the tendons, ligaments and fibrous portion of
      the joint capsules of equine stifles were determined by gross dissection. These
      sites of attachment were transposed onto one set of bones deprived of soft tissue
      and mapped using radiopaque markers. This specimen was then radiographed in the
      standard radiographic projections (lateromedial, caudocranial and caudal 60
      degrees lateral-craniomedial oblique) to determine the position of the attachment
      sites on the radiographs. RESULTS: Two radiographic maps were drawn per
      radiographic projection, one for the attachment sites of the ligaments and
      tendons and one for the attachment sites of the joint capsules. CONCLUSIONS AND
      POTENTIAL RELEVANCE: The radiographic maps of the precise position of the soft
      tissue attachments of the tendons, ligaments and joint capsules of the equine
      stifle should assist interpretation of equine stifle radiographs.

PMID- 16295929
TI  - Cross-sectional anatomy and comparative ultrasonography of the equine medial
      femorotibial joint and its related structures.
AB  - REASONS FOR PERFORMING STUDY: Injuries of the equine stifle are frequent causes
      of hindlimb lameness. Ultrasonography is useful for the diagnosis of many soft
      tissue lesions but, until recently, its application to the equine stifle has been
      limited to a description of normal and abnormal structures. A comparative study
      using gross anatomical sections to identify all structures visible on
      ultrasonographic images of the equine stifle has not previously been reported.
      OBJECTIVES: To provide a comprehensive comparative cross-sectional atlas of the
      normal equine medial femorotibial (MFT) joint and its related structures using
      ultrasonography. METHODS: The stifle joints of 15 cadaver limbs were examined
      ultrasonographically using a systematic approach. Ten different scanning planes
      were defined. The lateral and medial femorotibial and the femoropatellar joints
      were injected with pigments of different colours. Each leg was frozen (10 in
      extension and 5 in flexion) and cut into slices corresponding to the different
      scanning planes. According to the different ultrasonographic reference images, 10
      representative anatomical images were selected and digitised. RESULTS: All bony
      and soft tissue structures were identified on the anatomical sections and
      subsequently located on the corresponding ultrasonographic images, except the
      caudal meniscotibial ligaments. Visualisation of the cruciate ligaments was a
      challenge due to their position and oblique orientation. CONCLUSIONS:
      Ultrasonography is a very useful technique for imaging both soft tissue and bony
      structures of the MFT joint and its related structures, although a protocol is
      required to perform a systematic and standardised ultrasonographic examination.
      Good anatomical knowledge is mandatory for identification of the different
      structures. POTENTIAL RELEVANCE: This study should contribute to 1) knowledge of
      the ultrasonographic anatomy of the equine MFT joint and its related structures,
      2) use of a protocol for a standardised ultrasonographic examination and 3) the
      ability to recognise abnormal structures.

PMID- 16295931
TI  - Changes in location of centre of pressure and hoof-unrollment pattern in relation
      to an 8-week shoeing interval in the horse.
AB  - REASONS FOR PERFORMING STUDY: In order to optimise shoeing and shoeing
      conditions, it is essential to know how the horse adapts to a common shoeing
      interval. OBJECTIVES: To measure changes in location of the centre of pressure
      (CoP) and hoof-unrollment pattern during a shoeing interval and to assess whether
      these changes in CoP result directly from changes in hoof conformation or are
      also influenced by compensatory mechanisms. METHODS: Eighteen horses were trotted
      over a pressure-force measurement system shortly after shoeing and 8 weeks later.
      The position of the CoP was measured and also predicted using calculations based
      on changes in hoof conformation. RESULTS: The measured shift in CoP was less than
      calculated. This difference was largest in the hind feet. The hoof-unrollment
      pattern stayed basically the same in the front feet, but in the hind feet there
      was a substantial lateral shift of the trajectory of the CoP. CONCLUSIONS: Horses
      can compensate, to a certain extent, for changes in hoof conformation that
      develop during 8 weeks on shoes. As the capacity to compensate is less in the
      forelimbs, the relative increase in loading of these limbs during a shoeing
      interval is larger than in the hindlimbs. POTENTIAL RELEVANCE: This study
      provides essential basic data for the development of science-based shoeing
      techniques.

PMID- 16295932
TI  - Radiographic scoring lacks predictive value in inflammatory airway disease.
AB  - REASONS FOR PERFORMING STUDY: Diagnosis of inflammatory airway disease (IAD)
      currently rests upon the results of bronchoalveolar lavage (BAL) cytology, lung
      function testing and histamine bronchoprovocation (HBP), none of which provides
      direct information about structural change in the lung. HYPOTHESIS: That thoracic
      radiography might better portray structural change in the lungs and therefore
      offer a good clinical assessment of IAD. METHODS: A radiographic scoring system
      was developed to assess the extent of bronchial and interstitial pattern on
      thoracic radiographs in the dorsocaudal, dorsocranial and caudoventral regions in
      16 control horses and 33 horses with IAD. Mean scores were compared to ascertain
      whether thoracic radiographs could distinguish between the 2 groups. In order to
      determine whether independent observers reliably scored radiographs similarly, an
      inter-rater reliability score was employed for each radiographic observation.
      Correlations between radiographic scores, BAL cytology, lung function testing
      using the forced oscillatory technique and HBP were examined. RESULTS: Inter
      rater reliability was only moderate. Radiographic scoring demonstrated no
      differences between the 2 groups. There were no correlations among BAL cytology,
      lung function testing, HBP and radiographic scores. CONCLUSIONS AND POTENTIAL
      RELEVANCE: Thoracic radiographs are a low-yield diagnostic modality in horses
      with a clinical history compatible with IAD. In the absence of clinical evidence
      of more extensive, infectious disease, thoracic radiographs neither refine nor
      improve diagnosis of IAD, but increase diagnostic costs.

PMID- 16295933
TI  - Black walnut extract-induced laminitis in horses is associated with heterogeneous
      dysfunction of the laminar microvasculature.
AB  - REASONS FOR PERFORMING STUDY: Equine laminitis purportedly involves haemodynamic
      dysfunction at the level of the laminar vasculature. However, to date, no studies
      have been performed characterising the function of laminar arteries and veins
      during the prodromal stages of equine laminitis. HYPOTHESIS: That the prodromal
      stages of laminitis are associated with contractile dysfunction of the equine
      laminar vasculature. OBJECTIVE: To assess contractile function of laminar
      arteries and veins to phenylephrine (PE) and 5-hydroxytryptamine (5-HT). METHODS:
      Horses were administered black walnut heartwood extract (BWHE) or water (control
      horses) via nasogastric intubation. After euthanasia, laminar vessels (100-800
      microm internal diameter) were isolated and mounted on small vessel myographs to
      assess contractile function. RESULTS: Contractile responses to PE or 5-HT were
      identical in laminar arteries isolated from either control horses or those
      administered BWHE. In contrast, responses to PE or 5-HT were significantly
      reduced in laminar veins isolated from BWHE-administered horses when compared
      with laminar veins isolated from control horses. CONCLUSIONS AND POTENTIAL
      RELEVANCE: These results are consistent with the prodromal stages of laminitis
      being associated with selective dysfunction of laminar veins. Further studies are
      required to discern the precise nature of this dysfunction and its potential
      relevance to the pathogenesis of acute laminitis in the horse and possible
      therapeutic targets for treatment.

PMID- 16295935
TI  - Double blind, you are the weakest link--goodbye!

PMID- 16295934
TI  - Use of serum amyloid A and other acute phase reactants to monitor the
      inflammatory response after castration in horses: a field study.
AB  - REASONS FOR PERFORMING THE STUDY: Early recognition of excessive inflammation and
      infectious complications after surgery, leading to early institution of therapy,
      reduces post operative discomfort and facilitates recovery. Because serum amyloid
      A (SAA) is a highly sensitive marker of inflammation, measurements of SAA and
      other acute phase reactants in the equine surgical patient may be valuable in
      assisting clinical assessment of post operative inflammation. OBJECTIVES: To
      investigate changes in inflammatory markers after castration and to correlate
      levels of acute phase reactants with clinical severity of inflammation after
      castration. METHODS: Leucocyte numbers and blood levels of iron, SAA and
      fibrinogen were determined before castration and on Days 3 and 8 post operatively
      in 2 groups of horses; Group 1 (n = 11) had mild post operative inflammation and
      an uncomplicated recovery and Group 2 (n = 7) had local clinical signs of
      moderate to severe inflammation. RESULTS: Both groups had elevated serum SAA
      levels at Day 3 post operatively. In Group 1 concentrations had returned to
      preoperative levels by Day 8, whereas in Group 2 concentrations remained
      elevated. Plasma fibrinogen concentrations in serum increased to equal levels in
      both groups and stayed elevated throughout the study period. Serum iron
      concentrations of Group 1 did not change in response to castration, whereas
      concentrations in Group 2 decreased below preoperative levels on Day 8. Leucocyte
      numbers remained unchanged during the post operative period in both groups.
      CONCLUSIONS: Serum SAA and iron profiles reflected the course of inflammation and
      their levels correlated with the clinical severity of inflammation. In contrast,
      fever and changes in leucocyte numbers, which are usually considered to be
      hallmarks of inflammation and infection, were not useful for monitoring post
      operative recovery. POTENTIAL RELEVANCE: Measurements of SAA and iron may improve
      post operative monitoring. As sustained inflammation may indicate that the
      surgical wound has become infected, SAA and iron measurements may facilitate
      early recognition and hence early treatment of infection.

PMID- 16295936
TI  - Effect of a constant rate infusion of lidocaine on the quality of recovery from
      sevoflurane or isoflurane general anaesthesia in horses.
AB  - REASONS FOR PERFORMING STUDY: Lidocaine constant rate infusions (CRIs) are common
      as an intraoperative adjunct to general anaesthesia, but their influence on
      quality of recovery has not been thoroughly determined. OBJECTIVES: To determine
      the effects of an intraoperative i.v. CRI of lidocaine on the quality of recovery
      from isoflurane or sevoflurane anaesthesia in horses undergoing various surgical
      procedures, using a modified recovery score system. HYPOTHESIS: The
      administration of intraoperative lidocaine CRI decreases the quality of recovery
      in horses. METHODS: Lidocaine (2 mg/kg bwt bolus followed by 50 microg/kg
      bwt/min) or saline was administered for the duration of surgery or until 30 mins
      before the end of surgery under isoflurane (n = 27) and sevoflurane (n = 27).
      RESULTS: Horses receiving lidocaine until the end of surgery had a significantly
      higher degree of ataxia and a tendency towards significance for a lower quality
      of recovery. There was no correlation between lidocaine plasma concentrations at
      recovery and the quality of recovery. CONCLUSIONS: Intraoperative CRI of
      lidocaine affects the degree of ataxia and may decrease the quality of recovery.
      POTENTIAL RELEVANCE: Discontinuing lidocaine CRI 30 mins before the end of
      surgery is recommended to reduce ataxia during the recovery period.

PMID- 16295937
TI  - Behavioural assessment of pain in horses and donkeys: application to clinical
      practice and future studies.

PMID- 16295938
TI  - Arrhythmias and pregnancy.

PMID- 16295939
TI  - Cardiology in space.

PMID- 16295940
TI  - Intrapericardial cisplatin administration after pericardiocentesis in patients
      with lung adenocarcinoma and malignant cardiac tamponade.
AB  - INTRODUCTION: Patients with lung adenocarcinoma often suffer from metastatic
      pericardial effusion that may eventually cause cardiac tamponade. Recurrence of
      pericardial effusion is frequent after pericardial drainage and therapy for the
      prevention of fluid reaccumulation is still controversial. We evaluated the
      safety and effectiveness of the intrapericardial infusion of cisplatin, a
      substance with antineoplastic and sclerosing properties, after pericardiocentesis
      in patients with lung adenocarcinoma and malignant cardiac tamponade. METHODS:
      Twenty-five patients (19 males and 6 females, median age 55 years) with lung
      adenocarcinoma confirmed by cytological examination and cardiac tamponade were
      studied. All patients underwent subxiphoid pericardiocentesis through catheter
      insertion, under electrocardiographic, echocardiographic and haemodynamic
      guidance. After the malignant aetiology of the pericardial effusion had been
      confirmed by cytological examination, cisplatin was instilled (10 mg in 20 ml
      normal saline) into the pericardial cavity during three consecutive days.
      Clinical and echocardiographic evaluation was performed every month thereafter.
      RESULTS: Pericardial fluid of 350-1700 ml was removed (median 750 ml) and was
      haemorrhagic in 80% of the cases. Paroxysmal atrial fibrillation was detected in
      three patients (12%) and non-sustained ventricular tachycardia in two (8%). None
      of the patients had hypotension or retrosternal pain. One patient suffered from
      significant pericardial effusion reaccumulation (4%). Laboratory findings were
      not influenced by systemic drug absorption in any patient. Transthoracic
      echocardiographic study revealed pericardial thickening without physiology of
      constriction in 4 patients (16%). After pericardiocentesis, the mean survival
      period overall was 4.5 months (range 3-92 weeks), and mortality was attributed to
      widespread disease (respiratory failure). CONCLUSIONS: Intrapericardial
      administration of cisplatin is safe and effective in preventing the
      reaccumulation of malignant pericardial effusion in the majority of patients with
      lung adenocarcinoma.

PMID- 16295941
TI  - Drug-eluting stents: immediate and long-term results.
AB  - INTRODUCTION: In this study we present our findings from a series of patients who
      underwent coronary angioplasty and implantation of drug-eluting stents with
      rapamycin or paclitaxel. METHODS: Two hundred and twenty-three consecutive
      patients with 343 coronary lesions underwent angioplasty with implantation of 220
      rapamycin-eluting stents (Cypher) and 297 paclitaxel-eluting stents (Taxus).
      RESULTS: During the follow up period, 32 patients with 49 lesions had a new
      coronary angiographic examination because of ischaemia recurrence. The mean
      follow up time for these patients was 7.2 +/- 3.0 months (2.9-17.1 months). Seven
      patients showed angiographic restenosis (>50% diameter stenosis) in 9 lesions
      where stents had been implanted. The type of restenosis was focal in 7 of those
      lesions (in one it was multifocal), usually at the proximal edge of the stent. In
      2 lesions the restenosis was diffuse (1 in-stent, 1 extending beyond the stent
      margins). The incidence of major adverse coronary events was 4.4% (10 patients: 1
      death, 1 non-Q myocardial infarction, 1 Q myocardial infarction and 7 target
      vessel revascularisation procedures). CONCLUSIONS: Our findings demonstrate that
      drug-eluting stents can be used in routine clinical practice, regardless of the
      type of stenosis and the patients' clinical characteristics. The type of
      restenosis is mainly focal, though diffuse restenosis may also occur when complex
      lesions are treated with multiple stents.

PMID- 16295942
TI  - Efficacy and safety of oral amiodarone in controlling heart rate in patients with
      persistent atrial fibrillation who have undergone digitalisation.
AB  - INTRODUCTION: Oral amiodarone has been suggested by some authors for rate control
      in patients with persistent atrial fibrillation. In this study we evaluated the
      efficacy and safety of oral amiodarone versus placebo for rate control during
      exercise and daily activities in patients with chronic atrial fibrillation who
      had undergone digitalisation. METHODS: The study group consisted of 53 patients
      (35 men, mean age 65 +/- 9 years) with persistent atrial fibrillation (mean
      duration 17 +/- 7 months). All patients had therapeutic levels of digitalis and
      were under anticoagulation treatment with acenocoumarol. Twenty-eight of them
      were treated with amiodarone (200 mg per day orally) and 25 received placebo. All
      patients were assessed with 24-hour ECG monitoring, a maximal symptom-limited
      cardiopulmonary exercise test and evaluation of adverse events. RESULTS: The mean
      exercise duration was similar in both groups. Amiodarone produced a lower heart
      rate than placebo at all exercise levels (p<0.0001 for all). VO2 was similar in
      both groups whereas O2 pulse was higher in the amiodarone group at all exercise
      levels. During daily life, heart rate showed a significant circadian pattern in
      both groups, with higher values during the day than at night (time effect for
      both p<0.001). The mean value of heart rate under amiodarone was lower than for
      placebo (75 +/- 10 vs. 86 +/- 12/min, p<0.001) but this difference was due to a
      significant difference during the day (p<0.001) that was not present during the
      night (p =0.48). CONCLUSIONS: Oral amiodarone is very effective when combined
      with digoxin for control of heart rate in patients with chronic atrial
      fibrillation and it should be considered as an alternative treatment when more
      traditional drugs, such as Ca(+2) inhibitors or b-blockers have proven
      ineffective or are contraindicated.

PMID- 16295943
TI  - ST changes in dipyridamole pharmacological stress testing: do they have
      diagnostic or prognostic significance?

PMID- 16295944
TI  - Pulmonary thromboendarterectomy in chronic thromboembolic pulmonary hypertension.

PMID- 16295945
TI  - Treatment of a large rupture of the external iliac artery by implantation of a
      coated metal stent.

PMID- 16295947
TI  - Primary intramural fibroma of the left ventricle with a late apparent
      symptomatology.
AB  - We report a case of a 13-year-old girl who was admitted to the emergency
      department with syncope. She had been diagnosed in infancy with a large
      intramural fibroma of the left ventricle, but had been free of any clinical
      symptoms during the last decade. The patient underwent a thorough and detailed
      clinical and imaging study. We discuss the contribution of new non-invasive
      imaging modalities to the diagnosis of primary cardiac tumours and focus on the
      dilemmas of the paediatrician concerning the management of cardiac fibromas.

PMID- 16295946
TI  - Treatment of thrombosis of a mechanical aortic valve with fibrinolysis.
AB  - We describe the case of a 57-year-old man with a mechanical aortic valve who had
      discontinued oral anticoagulants for a long period and presented with symptoms of
      severe congestive heart failure, including pulmonary oedema and hypotension.
      Clinical and echocardiographic examination revealed a large thrombus obstructing
      the prosthetic valve. Since his critical clinical condition was not improved by
      heparin treatment we decided to administer intravenous fibrinolysis with 100 mg
      rtPA. Fibrinolytic treatment was entirely successful, with complete thrombus
      dissolution and restoration of clinical status. Thrombosis of mechanical
      prosthetic valves is a particularly serious complication with a high mortality
      rate. Early diagnosis and treatment are of paramount importance for these
      patients. Although surgical intervention is the suggested treatment in many
      series, fibrinolytic therapy offers a good alternative with a high success rate,
      especially in the critically ill patient where surgery carries a high risk of
      mortality.

PMID- 16295948
TI  - Radiofrequency catheter ablation for electrical storm in a patient with dilated
      cardiomyopathy.
AB  - We report a case of successful radiofrequency catheter ablation in a patient with
      dilated cardiomyopathy, who presented with multiple, haemodynamically poorly
      tolerated episodes of monomorphic ventricular tachycardia, resistant to
      antiarrhythmic drug treatment. The ablation procedure consisted of focal ablation
      of three mapped left ventricular sites, using pace and activation mapping.
      Additional linear ablation lesions were created across these sites. After the
      procedure, the patient remained free of tachycardia episodes and seven days post
      ablation he underwent implantation of a cardioverter-defibrillator. During a
      twelve-month follow-up period, the patient has remained free of monomorphic
      ventricular tachycardia episodes. Radiofrequency catheter ablation is feasible in
      electrical storm, using conventional mapping techniques, even in haemodynamically
      unstable tachycardias.

PMID- 16295949
TI  - Congenitally corrected transposition of the great arteries in a seventy-year-old
      woman.
AB  - Corrected transposition of the great arteries is a rare condition, and few
      patients with this abnormality survive past 50 years of age because of associated
      defects, or the subsequent development of atrioventricular valvular insufficiency
      or heart block or both. The case of our patient is of interest not only because
      she reached old age, but also because she lived a normal life, presenting with
      minor cardiac impairment and palpitations at the age of 70 years.

PMID- 16295950
TI  - There is no substitute for talent.

PMID- 16295951
TI  - The young cardiologist facing the renaissance of cardiovascular science.

PMID- 16295952
TI  - A call to action.

PMID- 16295953
TI  - The person behind the pain.

PMID- 16295954
TI  - From both sides now.

PMID- 16295955
TI  - Constructional apraxia in left brain-damaged patients: a planning disorder?
AB  - The aim of the present study was to verify the hypothesis advanced by Hecaen and
      Assal (1970), that the presence of landmarks can improve the copying performance
      of left brain-damaged patients, while leaving unchanged that of right brain
      damaged patients. Sixty-two control subjects and 196 brain-damaged patients with
      lesions restricted to the right (N = 84) or to the left (N = 112) cerebral
      hemisphere were given two tests of copying drawings. In the first task the
      patients were asked to directly copy a drawing; to perform the second test they
      were given guiding landmarks. On both tests no difference was found between the
      performance of the two hemispheric groups. Right-sided patients used a lower
      number of guiding landmarks, but this occurred only on the half of the drawings
      contralateral to the side of the lesion and was apparently due to unilateral
      spatial neglect.

PMID- 16295956
TI  - Impairment of facial recognition after closed head injuries of varying severity.
AB  - Perceptual matching of photographs of unfamiliar faces was studied in 46 patients
      with closed head injury. The severity of head injury as indexed by duration of
      coma and neurological deficits was inversely related to accuracy of performance.
      Impairment of facial recognition was specifically associated with signs of
      concomitant hemispheric and brain stem injury. The presence of neurologic
      deficits suggesting less pervasive injury essentially confined to the cerebral
      hemispheres, skull fracture, and EEG abnormality was not related to this
      visuoperceptive deficit. The findings are discussed in relation to hypotheses
      concerning neurological dysfunction in head injury.

PMID- 16295957
TI  - Factors related to prognosis of acquired aphasia in children.
AB  - In a follow up study of 15 children with acquired aphasia, it was found that the
      persistent presence of concomitant neurological disorders was important for the
      final outcome. Prognosis seemed to be related to etiology, EEG disturbances and
      the severity of comprehension deficit at the onset of aphasia.

PMID- 16295958
TI  - Perception of dichotic chords by normal and commisurotomized human subjects.
AB  - A perceptual suppression of an ipsilateral by a concurrent contralateral auditory
      signal occurs in commissurotomized subjects and probably in normal subjects. This
      suppression of the ipsilateral signal depends on the nature of the auditory
      stimuli. For dichotic speech sounds the suppression of the ipsilateral signal is
      overwhelming; for dichotically presented pure tones it is not present. For
      dichotically presented pure tones, unlike speech signals, a subcortical central
      pitch processor determines the contribution to the perceptual experience of the
      right and left ear signals in both normal as well as commissurotomized subjects.

PMID- 16295959
TI  - Memory function after closed head injury: a review of the quantitative research.
AB  - Studies which provide quantitative analyses of memory function following closed
      head injury were reviewed. Specific issues covered include criteria for assessing
      post-traumatic amnesia (PTA), PTA duration, relation of PTA duration to later
      memory impairment, memory functions within PTA, and comparisons between PTA and
      other amnesic conditions. Issues associated with the assessment of retrograde
      amnesia were also reviewed. With regard to memory function after PTA has
      terminated, we described and discussed normative data, the time course of
      recovery, and issues related to the nature of the later memory impairment.
      Directions for future work which seem particularly useful from a practical and
      theoretical viewpoint were also considered.

PMID- 16295960
TI  - Handedness and part-whole relationships: a replication.
AB  - Nebes' 1971 experiment reporting a deficit in the performance of left-handed
      subjects on a measure of part-whole relationships was replicated, controlling for
      family history of handedness and for experimenter knowledge of subject
      handedness. No differences were found for any comparisons. Results are examined
      in relation to similar failures to replicate, indicating that the arc-circle
      measure does not reliably discriminate any visual-spatial differences associated
      with handedness.

PMID- 16295961
TI  - Hemispheric specialization for linguistic and nonlinguistic tactual perception in
      a congenitally deaf population.
AB  - Two groups of congenitally deaf and two groups of hearing right-handed subjects
      identified pairs of nonsense shapes and letters after simultaneous bilateral
      tactual exploration. In response to shapes, left and right hand pointing to
      multiple choice arrays were compared. Three response modes, writing and left and
      right and fingerspelling, were compared for letters. A tendency for right tactual
      field superiority for shapes was observed in all groups. Groups initially exposed
      to letters showed significant right field superiority across response modes for
      shapes. No left-right asymmetries were observed for letters. Differences due to
      deafness were not observed.

PMID- 16295962
TI  - On the problems of speech compensation and fluctuating intellectual performance.
AB  - Some of the factors involved in compensation of speech deficits following local
      brain lesions are enumerated. An illustrative case is presented of a right-handed
      patient who failed to become aphasic despite massive resections for glioma from
      the left hemisphere. The surprising degree of speech intactness is discussed
      according to theories of interhemispheric transfer of speech function and the
      possibility that the right hemisphere had originally been the dominant hemisphere
      for speech, a so-called "ectopic speech center." It has been known for many years
      that an aphasic patient with a left hemisphere lesion has a better prognosis if a
      family history of left handedness is present. A sister of the patient reported
      here, although right-handed, is shown by dichotic listening studies to be right
      hemisphere dominant for speech. Thus, it is suggested that this finding on
      dichotic listening tests in a close relative may prove to be a favorable
      prognostic sign for compensation of the speech function. The patient also showed
      fluctuating intellectual performance and a curious "warming up" phase for the
      individual neuropsychological tasks. Data is presented from simultaneous
      neuropsychological testing and an integrated EEG frequency analysis which
      demonstrates an electrophysiological and behavioral correlation. The question
      arises as to whether the fluctuations frequently seen in brain-damaged patients
      might have a similar electrophysiological association.

PMID- 16295963
TI  - Laterality tests: an inferential problem.
AB  - A Baysean analysis is used to examine some of the inductive inferences about
      hemispheric "dominance" based on various laterality measures (e.g., dichotic
      listening). The results reveal some glaring errors of induction that may occur
      when inferences are made on constructs that have a low probability of occurrence
      in the population (i.e., right brain speech). The problem of measurement error
      and test validity is also discussed.

PMID- 16295965
TI  - The effect of prolonged pre-operative transfer testing on intermanual transfer of
      training in the monkey.
AB  - Prolonged transfer testing before surgery has been found not to facilitate
      intermanual transfer after commissure section in 2 rhesus monkeys.

PMID- 16295964
TI  - On the probability of pathological right-handedness.
AB  - The increased incidence of manifest left-handedness in retardates and epileptics
      has been attributed to a shift in handedness following early brain injury.
      Predictive models using this hypothesis have presumed an equipotentiality for
      shifts in hemispheric dominance whether a left or a right hemisphere is the
      originally dominant, injured hemisphere. This note demonstrates that the
      presumption of equipotentiality may be relaxed without significant effect upon
      the conclusions reached using the predictive models.

PMID- 16295966
TI  - Identifying facilitators and barriers to disclosure of sexual identity to health
      care providers.

PMID- 16295967
TI  - Legal barriers to accessing to health care in Kansas for same sex couples.

PMID- 16295968
TI  - Lesbian partner abuse: differences from heterosexual victims of abuse. A review
      from the literature.

PMID- 16295969
TI  - Providing culturally competent care to lesbians.

PMID- 16295970
TI  - Just do the right thing.

PMID- 16295971
TI  - Reduce your no-shows--money-losers to your practice.

PMID- 16295972
TI  - "You've come a long way, doctor!".

PMID- 16295973
TI  - Frequently asked questions about billing for critical care services.

PMID- 16295975
TI  - Prescribing physical activity for older adults.
AB  - Physicians and other healthcare providers must disseminate the message promoting
      physical activity among all of their patients, especially frail older adults.
      Some degree of physical activity is always preferable to a sedentary life. The
      goals of physical activity counseling are to provide concrete information, clear
      and consistent recommendations, and to recognize barriers that older adults face
      in initiating and maintaining a program. Tailoring the message based on their
      patient's health and functional status is paramount and counseling should be
      ongoing and included at every visit. Focusing on what has been described as
      "functional fitness," such as walking, transferring (up and down from chair, in
      and out of car, up and down stairs) in order to more easily complete tasks of
      daily living, should also be stressed. Medical school curricula will need to
      address this deficiency of practicing physicians by enhancing this area of
      training for optimal disease prevention, chronic disease management and health
      promotion.

PMID- 16295974
TI  - Closing the vaccine gap among toddlers in N.J. family physicians' practices.

PMID- 16295976
TI  - OSMA and Oklahoma Medicine, 1946-1955.

PMID- 16295977
TI  - "The future ain't what it used to be".

PMID- 16295978
TI  - Preconception health: a public health challenge.
AB  - Minimal attention has been paid to preconception counseling even though good
      preconception health may be among the most important segments of a woman's life.
      Only in recent years have most healthcare providers, including obstetricians,
      realized that the initiation of health care and guidance after conception may be
      too late to prevent birth defects, low birthweight and infant mortality. The
      Oklahoma State Department of Health's Birth Defect Registry has developed a
      Women's Health Appraisal Questionnaire to assist physicians in identifying high
      risk behaviors and other condition in the patient's environment that may be
      linked to detrimental outcomes to the fetus. The Women's Health Questionnaire can
      be offered to women of childbearing age in the waiting rooms of health clinics.
      The questionnaire takes about three to five minutes for the patient to complete.
      Free English and Spanish versions of the Women's Health Appraisal Questionnaire
      and other preconception tip booklets are being offered to physicians and health
      departments in Oklahoma. To order the preconception health questionnaire and
      booklets, there is an order form included in this journal.

PMID- 16295979
TI  - Patient handout. Wellness tips for all women. Before you stop your method of
      birth control.

PMID- 16295980
TI  - Patient handout. Women's health appraisal questionnaire forms and patient
      booklets.

PMID- 16295981
TI  - Patient page #63. Ovarian cancer. What you need to know!

PMID- 16295982
TI  - Rural immersion as an instructional method in northern community health.
AB  - In 2004, a class of six students traveled with three faculty mentors to seven
      Alaska communities as part of a course designed to ground young researchers'
      aspirations in the pragmatics of collaborative, community-based research. This
      paper, authored by the students involved, discusses the process from start to
      finish. Beginning researchers in rural health are often daunted not by a lack of
      ability or ideas, but by basic issues of logistics, trust and respect.
      Unfortunately, they tend to remain unacquainted with these considerations until
      something goes wrong, and come to frame the research process as a succession of
      hindrances to be overcome rather than a fluid and collaborative endeavor. By
      placing students in working relationships with rural residents and Native elders
      at an early stage, the project aims to minimize common missteps and shorten the
      learning curve. It is hoped that our experiences can point the way toward similar
      efforts.

PMID- 16295984
TI  - From out of the past...30 years ago.

PMID- 16295983
TI  - Tobacco use during pregnancy among Alaska Natives in western Alaska.
AB  - OBJECTIVE: To determine tobacco use rates during pregnancy among Alaska Natives
      residing on the Yukon-Kuskokwim (Y-K) Delta of western Alaska. Alaska Natives
      residing in this region use Iqmik, a unique form of smokeless tobacco (ST). STUDY
      DESIGN: Retrospective cohort study. The medical records of the most recent
      consecutive 100 Alaska Native women delivering within the Y-K Health Corporation
      system in 2001 were abstracted for information on tobacco use during this
      pregnancy and basic demographics. RESULTS: Of the 100 women, 24 did not use
      tobacco, 55 used ST only, 18 smoked cigarettes only, and 3 used both ST and
      smoked cigarettes during this pregnancy. Of the 58 who used ST, 22 used Iqmik
      only, 32 used commercial ST only, and 4 used both. The frequency of ST use
      increased significantly with age (p=0.007; OR=1.65 per 5-year increase in age,
      95% CI 1.15 to 2.36), while the frequency of cigarette smoking tended to decrease
      with age (p=0.254; OR=0.79 per 5-year increase in age, 95% CI 0.53 to 1.18).
      CONCLUSION: A high proportion of Alaska Native women use tobacco during
      pregnancy. The rate of ST use (58%) among pregnant Alaska Native women is
      markedly higher than the prevalence of ST use (0.5%) among women in the general
      U.S. population.

PMID- 16295985
TI  - Peptic ulcer disease in the Alaska Natives: a four-year (1967-1971) retrospective
      study.
AB  - A four-year retrospective study of peptic ulcer disease in the Alaska Native
      confirmed our suspicion of a decreased ratio of duodenal to gastric ulcers. There
      were 92 patients with duo-denal ulcers, 75 with gastric ulcers, 6 with carcinoma
      of the stomach and 1 with gastric sarcoma. Ulcer disease in the Alaska Natives
      differs from ulcer disease among the Southwestern Indians as reported by Sievers.

PMID- 16295986
TI  - Don't tip the scales! Care for patients involved in a police investigation.
AB  - Occasionally perioperative nurses are involved in the complex role of caring for
      medical-legal evidence while also advocating for the patient's right for privacy.
      Appropriate management of evidence may be the deciding factor in the outcome of a
      criminal investigation. Understanding the importance of evidence is the first
      step in learning how to prevent its unintentional destruction during the surgical
      procedure. Our first consideration with every patient is to provide safe and
      efficient care. In the OR, cooperation with the police is balanced with the
      patient's right to privacy and confidentiality of their health care information.
      This is not always an easy task. Perioperative nurses have a responsibility to
      their patients as well as to investigators to do what is appropriate, since our
      actions can have direct effects on the outcomes of criminal investigations.
      Understanding the importance of evidence is the first step in learning how to
      keep evidence from being destroyed. Hospital documentation is often accepted in a
      court of law without challenge.

PMID- 16295988
TI  - Message from the president: a personal encounter with healthy work environments.

PMID- 16295987
TI  - Disposable surgical face masks: a systematic review.
AB  - Surgical face masks were originally developed to contain and filter droplets of
      microorganisms expelled from the mouth and nasopharynx of healthcare workers
      during surgery, thereby providing protection for the patient. However, there are
      several ways in which surgical face masks could potentially contribute to
      contamination of the surgical wound. Surgical face masks have recently been
      advocated as a protective barrier between the surgical team and the patient, but
      the role of the surgical face mask as an effective measure in preventing surgical
      wound infections is questionable. The aim of the systematic review is to identify
      and review all randomised controlled trials evaluating disposable surgical face
      masks worn by the surgical team during clean surgery to prevent postoperative
      surgical wound infection. All relevant publications about disposable surgical
      face masks were sought through the Specialised Trials Register of the Cochrane
      Wounds Group (March 2001). Manufacturers and distributors of disposable surgical
      masks as well as professional organisations including the National Association of
      Theatre Nurses and the Association of Operating Room Nurses were contacted for
      details of unpublished and ongoing studies. Randomised controlled trials (RCTs)
      and quasi-randomised controlled trials comparing the use of disposable surgical
      masks with the use of no mask were included. MAIN RESULTS: Two randomised
      controlled trials were included involving a total of 1453 patients. In a small
      trial there was a trend towards masks being associated with fewer infections,
      whereas in a large trial there was no difference in infection rates between the
      masked and unmasked group. Neither trial accounted for cluster randomisation in
      the analysis. REVIEWERS' CONCLUSIONS: From the limited results it is unclear
      whether wearing surgical face masks results in any harm or benefit to the patient
      undergoing clean surgery.

PMID- 16295989
TI  - Collins on current issues: health care communication.

PMID- 16295990
TI  - Fostering respectful collaboration through communication.

PMID- 16295991
TI  - Healthy communication in the healthcare environment.

PMID- 16295992
TI  - Effective communication with patients.
AB  - This brief article aims at heightening awareness about communication with various
      patients, including strategies to assist in improving communicative
      effectiveness. It assists us as health care professionals to go back to basics
      and reflect on how we communicate. Several researchers have provided insight into
      ways that communication may be enhanced. Walter, Bundy, and Donan (2005)
      suggested personally greeting the patient, introducing oneself, engaging in talk
      about clinical concerns, and then discussing next steps toward healthcare
      solutions. Schillinger (2003) implored that health related jargon be avoided and
      that all messages be clear and simple. Illustrations in the form of black-white
      line drawn pictures also tend to assist in patient comprehension. Lawton and
      Carroll (2005) suggested that effective communication requires assessing what the
      patient knows about their illness. Seidel's model (2004) stated that healthcare
      providers listen to the patient's story and elicit information through
      questioning with sufficient time allotted to provide answers. He also discussed
      the importance of providing a short summary of what the patient conveyed and
      giving additional information so they learn more about what is happening to them
      and can become an active participant in making decisions. It is important that
      patients understand what we as healthcare professionals say to them. Wisner
      (1999) further conveyed that it is not words alone that communicate. Body
      language, facial expressions, and tone of voice often provide additional clues
      influencing communicative effectiveness. Without a doubt, communication, directly
      impacts service delivery and quality of care in healthcare today. Listen to your
      patients, they have much to say.

PMID- 16295994
TI  - Your $5 bucks can go the distance for a year with PAC. Interview by Carol
      Forrester-Staz.

PMID- 16295995
TI  - Early risk patterns in substance abuse impaired nurses.

PMID- 16295996
TI  - A validated, model-specific tool to measure the developmental stage of a shared
      governance, professional practice model.

PMID- 16295997
TI  - Pain management: it is time to move beyond numbers.

PMID- 16295998
TI  - Pilates for nurses.

PMID- 16295999
TI  - Toxic chemicals in i.v. tubing.

PMID- 16296000
TI  - Ask the doctor. I had a blood test for CRP that came back at 1.9, which my doctor
      said was on the high side. I had it checked again a few weeks later and it was
      under 1. What does this mean? Should I have it checked again?

PMID- 16296001
TI  - Folate transport and the modulation of antifolate sensitivity in a methotrexate
      resistant human breast cancer cell line.
AB  - The mechanism of acquired methotrexate-resistance in an estrogen-receptor
      positive human breast cancer cell line (MTX(R)ZR-75-1) was studied. MTX(R) ZR-75
      1 cells are 250-fold resistant to methotrexate when grown in the presence of 1
      microM folinic acid and 2,400-fold resistant in the presence of 1 microM folic
      acid. This drug resistant cell line also showed collateral sensitivity (10-fold)
      to trimetrexate (TMQ), when grown in the presence of folinic acid. Using
      fluoresceinated methotrexate (F-MTX), FACS analysis indicated that there is no
      intracellular accumulation of methotrexate into MTX(R) ZR-75-1 cells, as
      determined by competition of F-MTX and methotrexate binding to dihydrofolate
      reductase. These characteristics strongly indicate that the mechanism of
      resistance involved down regulation of the reduced-folate transporter. To
      investigate this further, the transport kinetics of parental and MTX(R) ZR-75-1
      cells were examined. Although the V(max) for methotrexate transport in wild-type
      (WT) ZR-75-1 breast cancer cells was 1-2 orders of magnitude lower than that in
      the well characterized leukemia cell lines, such as L1210 and CCRF-CEM cells,
      kinetic analysis indicated that transport of methotrexate into WT ZR-75-1 cells
      involved a mechanism that was similar if not identical to the reduced folate
      transporter. In contrast, no specific uptake of methotrexate was detected in
      MTX(R) ZR-75-1cells. Furthermore, neither cell line expressed detectable levels
      of folate binding protein, a binding protein with high affinity for folic acid as
      well as for reduced folates and antifolates. These results indicate that the
      level of expression of the reduced-folate carrier may be an important factor in
      determining the sensitivity of breast cancer cells as well as leukemia cells to
      antifolate compounds.

PMID- 16296003
TI  - Influence of extracellular pH on the accumulation and cytotoxicity of N-(4
      methylphenylsulfonyl)-N'-(4-chlorophenyl)urea in human cell lines.
AB  - The effect of extracellular pH (pH(e)) on the accumulation and cytotoxicity of
      the diarylsulfonylurea antitumor agent N-(4-methylphenylsulfonyl)-N'-(4
      chlorophenyl)urea (MPCU) has been examined. In a human colon adenocarcinoma cell
      line, GC3/C1, the initial rate of uptake of [3H]MPCU (2.4 microM) was increased
      by 4.5-fold as pH(e) was reduced from 7.4 to 6.5. Steady state levels of MPCU
      were inversely proportional to pH(e) and were 5-fold greater at pH 6.0 compared
      to 7.4. Similar results were obtained using Rh30 cells derived from an alveolar
      rhabdomyosarcoma. MPCU rapidly re-equilibrated after achieving steady state when
      pH(e) was altered, indicating that MPCU was not tightly bound within cells. In
      both cell lines, the uncoupling agent, carbonylcyanide p
      trifluoromethoxyphenylhydrazone (FCCP), significantly reduced (GC3/C1) or
      completely inhibited (Rh30) accumulation of MPCU at each pH(e) examined. Sodium
      azide had the same effect on the accumulation of MPCU as FCCP. The effects of
      FCCP and azide appeared to be due to collapse of the pH differential across the
      mitochondrial inner membrane rather than the gradient across the plasma membrane.
      As extracellular pH (pH(e)) decreased, intracellular pH(pH(i)) also decreased in
      GC3/C1 cells, such that the greatest pH differential (pH(i) - pH(e)) was 0.2
      units at pH(e) 6.0. Neither FCCP nor azide significantly altered this pH
      gradient, indicating a minor role, if any, for the plasma membrane pH gradient in
      accumulation of MPCU in GC3/C1 cells. The effect of pH(e) (7.4 to 6.0) on
      cytotoxicity of MPCU was determined after exposure of cells for 4 hr to various
      concentrations of MPCU in the presence of 10% fetal bovine serum. Decreasing the
      pH(e) from 7.4 to 6.0 increased the potency of MPCU by 4.7- and 4.5-fold in Rh30
      and GC3/C1 cells, respectively. In cells exposed to drug/pH(e) combinations that
      resulted in 50% reduction in colony forming potential, the steady state levels of
      [3H]MPCU were similar (range 8.8 +/- 0.9 to 10.56 +/- 0.6 nmol/10(6) cells).
      These results demonstrate that decrease of pH(e) significantly enhanced the
      uptake of MPCU accumulation into an FCCP/azide-sensitive compartment, and
      cytotoxicity of this agent. These data further support the hypothesis that
      sequestration of diarylsulfonylureas into the FCCP/azide-sensitive compartment
      (probably mitochondria) was associated with its cytotoxicity. The role of pH(e)
      in determining therapeutic selectivity of diarylsulfonylureas is discussed.

PMID- 16296002
TI  - Effect of nucleoside transport inhibitors on thymidine salvage and the toxicity
      of nucleoside analogs in mouse bone marrow granulocyte-macrophage progenitor
      cells.
AB  - In an attempt to elucidate the types of nucleoside transporters present in bone
      marrow stem cells, this study examined the effect of nucleoside transport
      inhibitors on the toxicity of nucleoside analogs and on the salvage of thymidine
      by mouse bone marrow granulocyte and macrophage progenitor cells using the CFU-GM
      assay. Concentrations of NBMPR (nitrobenzylmercaptopurine riboside) as low as 10
      nM protected these cells from the toxicity of the adenosine analog tubercidin and
      provided a partial block of thymidine-rescue of the granulocyte-macrophage
      progenitor cells from methotrexate toxicity. Dipyridamole had similar effects but
      generally required higher concentrations. These results suggested that the major
      nucleoside transporter in these cells is the NBMPR-sensitive equilibrative
      carrier, es. In contrast to the results with tubercidin, the toxicity of 2
      chlorodeoxyadenosine was increased 8- to 10-fold by 1 microM NBMPR. These results
      suggested that the bone marrow granulocyte-macrophage progenitor cells also have
      a concentrative nucleoside transporter that is capable of pumping 2
      chlorodeoxyadenosine into the cells while efflux of the nucleoside via es is
      blocked by NBMPR.

PMID- 16296004
TI  - Post-translational processing of purified human K-ras in Xenopus oocytes.
AB  - Membrane localization of ras p21 involves a complex series of post-translational
      processing events, including S-farnesylation of Cys-186, removal of three
      carboxyl-terminal amino acid residues, and methylation of the carboxyl-terminal
      farnesylcysteine residue. Palmitoylation of cysteine residues within the
      hypervariable region (amino acids 165-185) is also required for membrane
      localization of mammalian H-, N-, and K-ras(A). For K-ras(B), which contains no
      cysteine residues within the hypervariable region, a polybasic domain substitutes
      for palmitoylation as a second signal for plasma membrane targeting. In order to
      investigate the localization of K-ras(B) to the plasma membrane, we purified wild
      type and mutant human K-ras(B) proteins from strains of E. coli harboring
      bacterial expression plasmids and injected them into Xenopus laevis oocytes. Our
      results show that wild-type and activated K-ras(B) proteins can be post
      translationally modified and can induce meiotic maturation in Xenopus oocytes. A
      mutation at Cys-186 (Cys to Gly) abolished the ability of activated K-ras(B) to
      induce meiosis. Deprivation of isoprenyl precursors by the addition of
      lovastatin, a drug that blocks the synthesis of mevalonate, also abolished the
      ability of activated K-ras(B) to induce meiosis, although this inhibition could
      be overcome by the addition of exogenous mevalonate. Lovastatin did not block
      meiotic maturation induced by microinjection of purified mos protein, a component
      of the cytostatic factor that arrests Xenopus oocytes at the first meiotic
      prophase. These results indicate that post-translational isoprenylation of K
      ras(B) is essential for plasma membrane targeting and induction of meiotic
      maturation in Xenopus oocytes and that further isoprenyl modification of proteins
      downstream from mos signal transduction is not essential for this process.

PMID- 16296005
TI  - Some specific features of the regulatory mechanisms of transcapillary exchange
      and tissue trophism.

PMID- 16296006
TI  - Regional differences in the relationship between vessels and tissues: importance
      of glycosamino-glycans.

PMID- 16296007
TI  - Permeability of high weight molecules in the cardiovascular collapse.

PMID- 16296008
TI  - Relationship between coronary resistance, a redox potential across the heart and
      myocardial consumption of lactate and oxygen.

PMID- 16296009
TI  - Application of the fluorescent method for analysing microcirculation and
      metabolism in the myocardium.

PMID- 16296010
TI  - Peculiarities of microciirculation and reparative processes in the development of
      experimental myocardiail infarction.

PMID- 16296011
TI  - Coronary vasoconstriction as a cause of angina pectoris at rest documented by
      angiography and by regional myocardial perfusion radioisotopic studies.

PMID- 16296012
TI  - Microcirculatory changes in acute disturbances of brain circulation.

PMID- 16296013
TI  - Reactivity of the cerebral resistance and capacitance vessels and blood-brain
      water exchange in the experimental brain injury.
AB  - In conclusion, an estimate of the intracranial volumetric effects produced in
      anesthetized dogs by histamine, acetylcholine and CO2 shows that, on a basis of
      equiactivity on CBF, the effects of histamine on the intracranial content are
      twice greater than those produced by acetylcholine and CO2. This difference may
      be explained by a greater activity of histamine on the intracranial capacitance
      vessels and/or by an increase in the fluid escape from blood to the brain
      produced by histamine. Data obtained after the production of an acute, cold
      induced brain lesion support the second possibility.

PMID- 16296015
TI  - Platelet emboli and ischemia in rabbit's brain caused by ADP or arachidonic acid
      and the protective effect of ASA and dipyridamole.

PMID- 16296014
TI  - Changes in brain circulation in acute coronary insufficiency.

PMID- 16296016
TI  - Blood vessels - a selfadjusting construction: changes in long-term hypotension.

PMID- 16296017
TI  - Efficiency of the capillary blood flow in the skeletal muscles with vasodilation
      in a limb.

PMID- 16296018
TI  - Reactive hyperemia in Raynaud's disease.
AB  - We studied reactive hyperemia after ischemia, after cold, and after cold plus
      ischemia, in normal subjects, in fingers with Raynaud's phenomenon, and in
      fingers without Raynaud's phenomenon in hands where other fingers were affected
      by Raynaud's phenomenon. The results obtained demonstrate the existence of a
      criohyperdysestesia both in fingers with Raynaud's phenomenon and in fingers
      without Raynaud's phenomenon in hands where other fingers are affected by it.

PMID- 16296019
TI  - Microangiology in the "macrophlebopathies".

PMID- 16296020
TI  - Applying Kohlberg's theory of moral development in group care settings.

PMID- 16296021
TI  - Joint custody and co-parenting: not by law but by love.
AB  - In recent years, joint custody and co-parenting of children after divorce or
      separation has received considerable attention. The authors advocate wider
      recognition of this option to sole custody and visitation, review pertinent legal
      and other literature, identify indications and contraindications, and briefly
      discuss the implications for social workers.

PMID- 16296022
TI  - Investigation of incest: opportunity to motivate families to seek help.
AB  - Incest, like other forms of sexual abuse, is a criminal act that society treats
      ambiguously. Victims are doubly victimized by being subjected to disbelief on the
      part of those who should protect them. Presented here is a modelfor investigation
      that not only leads to protection for the victim and prosecution for the
      perpetrator, but guides the family to take steps toward resolving their problem.

PMID- 16296023
TI  - Helping black grandparents and older parents cope with child rearing: a group
      method.
AB  - The extended family and informal adoption practices of the black culture are
      frequently misunderstood by workers from different backgrounds. Particularly
      prominent is the responsibility for child rearing assumed by older family
      members. The authors present procedures, issues, and argument for use of a group
      method to strengthen the coping abilities of these families through attention to
      the needs of their senior members.

PMID- 16296024
TI  - Child guidance as perceived by foster parents and social workers --a research
      note.
AB  - A brief report of findings from a regional study into the conflict and confluence
      between the attitudes of foster parents and social workers on children's
      developmental characteristics points to the need for greater discussion of
      guidance issues between these groups and further research into the nature and
      effects of their perceptual differences.

PMID- 16296025
TI  - [Investigations on live vaccine against pig salmonellosis].
AB  - The purpose of the work was to determine pathogenic properties for guinea-pigs of
      of S. choleraesuis-Ivanovice (the attenuated strain used for the production of
      live vaccine) and S. choleraesuis no. 964 (the virulent strain used for infection
      of pigs under experimental conditions). The effectiveness and safety of the live
      vaccine prepared from the Ivanovice strain was also tested in pigs under
      laboratory and field conditions. The results of the experiments showed that both
      strains can be differentiated by subcutaneous, intramuscular and intraperitoneal
      inoculations of guinea-pigs. This finding is especially important for the routine
      state control of the vaccine, containing the Ivanovice strain. Field and
      laboratory experiments showed that the vaccine is effective and safe for pigs
      kept in fattening centres. Salmonellae contained in the vaccine were not excreted
      in faeces of vaccinated pigs. The serum agglutination titre ranged from 256 to
      1024, 14 days after vaccination. No salmonellae were found in internal organs,
      lymph nodes and bone marrow 1-6 months after vaccination. The vaccinated pigs
      were fully protected against infection with the virulent S. choleraesuis strain
      under laboratory conditions. The immunity lasted 4 months. Most vaccinated pigs
      shed salomonellae in faeces for 10 days after infection, but later no shedding
      was observed. No salmonellae were isolated from internal organs of immunized pigs
      2 months after infection, except in 1 out of 12 pigs tested, in which salmonellae
      were found in the caecum.

PMID- 16296026
TI  - [The antibiotic sensitivity patterns of Salmonella pullorum and Salmonella
      gallinarum in in vitro studies].
AB  - The antibiotic sensitivity patterns of 100 strains of S. pullorum and 24 strains
      of S. gallinarum against 19 antibiotics and 3 antibiotic mixtures were determined
      by the broth dilution method. The strains studied were isolated from enzootic
      outbreaks of pullorum disease and fowl typhoid. It was found that all the strains
      were sensitive to ampicillin, streptomycin, neomycin, kanamycin, oxytetracycline,
      chloromycetin, gentamycin, signamycin, polzomycin, and neotarchocin. Besides, S.
      pullorum was sensitive to aureomycin. In vitro studies showed that polzomycin and
      neotarchocin appeared to be the most effective drugs in the treatment of poultry
      diseases caused by S. pullorum or S. gallinarum. The appearance of high
      percentage of S. pullorum and S. gallinarum strains resistant simultaneously to
      several antibiotics points to the necessity of the determination of antibiotic
      sensitivity patterns of salmonellae isolated from birds.

PMID- 16296027
TI  - [Immunofluorescent studies with IBR/IPV virus on cell culture].
AB  - The anti IBR/IPV virus (FITC labelled) conjugate was prepared from the bull's
      hyperimmune serum according to the method applied in CVL Weybridge for
      preparation of anti-Swine-Fever Conjugate (anti genital strain of virus). The
      conjugate was titrated using Calf Kidney primary monolayers grown on coverslips
      in Leighton tubes and inoculated with "Oxford" and "Carmarthen" strains of
      IBR/IPV virus. The conjugate was active for the first strain in dil. 1:16 and for
      the second in dil. 1:8. The specificity of reagent was checked both with strains
      of IBR/IPV viruses and other Herpesviruses: Aujesky Disease and Bovine Mammalitis
      and heterological conjugates (TGE, HCV). The morphological changes of infected
      cells and development of specific fluorescence were studied against the increase
      of extracellular viral titres. The time of appearance of specific fluorescence
      following inoculation of cells with a low, specially selected virus cell
      multiplicity ratio = 0.22 was 12-16 hours p.i. which corresponded to viral liter
      of fluid 1.0 [- log TCID50/-0.1 ml]. The visible CPE occurred at 32-36 hours
      after infection. The possibility of application of the above-mentioned conjugate
      to immunofluorescent studies with cells infected by IBR/IPV virus was confirmed.

PMID- 16296028
TI  - [Investigations on the application antigens for CFT to the diagnosis of
      infections in cattle and sheep caused by Chlamydia germs].
AB  - Studies were carried out to evaluate and choose the best methods to produce
      Chlamydial antigens for CFT. The antigens were prepared by the following 4
      methods: Beer's method using placentas of ewes infected with Chlamydia: from
      infected chicken embryos by means of an original own method and by the method of
      Gyulai at al. (as modified by the author); by the author's method using bull
      testicles infected with orchitis granulomatosa. Chlamydial antigens obtained in
      these experiments were active in CFT with some positive Chlamydial sera. The
      results obtained indicated that the method of Gyulai at al. as modified by the
      author would be the most useful one under Polish conditions for the production of
      Chlamydial antigen used in CFT. This test was used for serological diagnosis of
      Chlamydia infections in cattle and sheep.

PMID- 16296029
TI  - [Agglutinative and phagocytic reaction in pregnant cows vaccinated against
      colibacteriosis, as well as in new-born calves].
AB  - The aim of the work was investigation on some body reactions in cows and calves
      against an introduced antigen or a non-specific stimulus. The tests were carried
      out on vaccinated pregnant cows, on cows treated with a non-specific stimulus,
      and on new-born calves. The vaccine was prepared from an isolated strain of
      Escherichia coli found in the cowhouse under examination. Boiled milk constituted
      the non-specific stimulus. The body response to the introduced antigen was tested
      by agglutination and phagocytic reaction. For both reactions a homologous strain
      as well as heterologous strains were used. The findings prove that vaccination
      with autovaccine of the cows in the second half of the pregnancy period affects
      the increase of antibody level in the sera of immunized cows, in their beestings
      and in their new-born calves. Stimulation in an optimal period before calving has
      a similar effect shown by a higher level of antibodies in the stimulated cows as
      well as in their offsprings. The period, of antibody persistence in the blood
      sera of the calves depends on their initial level formed under the influence of
      an early imbibition of their first beestings. The calves were born with a high
      cellular immunity, in contradistinction to the humoral one.

PMID- 16296030
TI  - [Studies on the method of removing foreign bodies from the reticulum with the use
      of the Eisenhut probe].
AB  - So far a number of different opinions have been published in various publications
      on the possibilities of preventing diseases caused by foreign bodies--by removing
      them from the reticulum with the use of the magnetic probe. It was decided to
      test the practical value of the Eisenhut probe. Studies on 58 cows were carried
      out in the 1967-1973 period. Among the tested animals fere those suffering
      persistent rumen fistula and others which were being examined after rumenotomy.
      The animals under observation were divided into 5 groups. The object of the
      experiment was to test: a) the properties of the probe and possible dangers which
      might have resulted from its application. b) the usefulness and effectiveness of
      this rather expensive instrument. On the strength of experiments carried out it
      was found that the possibilities in moving the end of the probe, when introduced
      into reticulum, are very limited and, what more, a direct application of that
      into the reticulum cavity is difficult in "mass-probing", thus largely
      restricting the efficiency of the given instrument. The "retrieving crown" of the
      magnetic end has no essential part in the process of removing foreign bodies from
      the reticulum. Results obtained after having starved the animals for a period of
      time were even worse. When applying the probe to animals in good health, cases of
      rupturing the oesophagus and thus aspiring the alimentary content into the
      respiratory tract were recorded. When using the above-mentioned instrument, it
      was never possible to recover more than 50% of the foreign bodies introduced
      previously into the reticulum, which was mainly due to the difficulty in
      introducing the magnetic end into the reticulum.

PMID- 16296031
TI  - [Studies on the appearance of chalone proteins in the subcellular fractions from
      some bovine tissues. I. Antimitotic activity, the level of proteins, nucleic
      acids and glycoproteins in healthy cattle and in that affected with leukosis].
AB  - The occurrence of chalones has been studied in the liver, spleen and lymph nodes
      of cattle. The cells of those organs were fractionated. After removing the nuclei
      and mitochondria the residue was subdivided by means of the cesium chloride
      gradient into smooth and rough microsomes. The chalones were investigated in
      supernatants from these two groups of microsomes. In the obtained supernatants,
      the levels of proteins, nucleic acids and glycoproteins were estimated. The
      protein composition was analysed by means of disc electrophoresis on
      polyacrylamide, and the antigenic relationship of these proteins with the serum
      ones was studied using immunoelectrophoresis. The biological value of the
      separated fractions was investigated by means of the mitosis inhibition test in
      mice. The experimental groups of these animals were injected intraperitoneally
      with different cellular subfractions without or with colcemide. The control
      groups were treated with colcemide only or with physiological solution of NaCl.
      The subcellular fractions were separated from the tissues of healthy cattle and
      of that affected with leukosis. It was found that a protein showing chalone
      activity appears in all cellular subfractions derived from the tissues of healthy
      animals; its highest concentration was found in the supernatants from rough
      microsomes of the spleen and from smooth microsomes of the lymph nodes. The
      antimitotic effect was observed at the concentration of 100-200 microg of protein
      in 0.1 ml. This effect seems to be connected with glycoproteins. In the
      supernatants from tissues of leukotic animals, there was observed a decrease of
      the antimitotic effect. A mixture of proteins was present in the supernatants,
      which was demonstrated by means of polyacrylamide electrophoresis. These proteins
      showed and antigenic relationship with the proteins of blood serum. This can be
      concluded from their precipitation with the sera against the bovine serum
      proteins in the immunoelectrophoresis test. The chalone of the spleen seems to be
      different from that of the lymph nodes. The experiment showed the occurrence of
      an antimitotic effect with the non-homologous proteins, i.e. the chalone from the
      liver inhibited the mitotic divisions of the cells of the spleen, thymus and
      lymph nodes in mice. In this experiment, a mixture of proteins was used. The
      purification of an active chalone will be the subject of further investigations.

PMID- 16296032
TI  - Studies on the appearance of chalone proteins in subcellular fractions from some
      bovine tissues. P. II Attempt of isolation of intracellular glycoproteins
      (chalone) from bovine spleen.
AB  - In the course of purification of chalone deriving from the subcellular fractions
      of bovine spleens, the butanol extraction of smooth and rough microsomes
      supernatants was performed. After extraction the lower layer was treated with
      SDS, buffered at pH 5,8. The homogeneity of obtained fractions was investigated
      by means of polyacrylamide electrophoresis. The antimitotic activity of fractions
      was performed by colcemide test in mice. There was stated that the cells of
      spleen contained two chalones. One of them showed antimitotic activity towards
      spleens of mice, the other towards lymph nodes. The former revealed on the
      polyacrylamide gel the mobility of gamma or beta, globulins, the later of
      prealbumins.

PMID- 16296033
TI  - [Influence of coumarin on the lipolytic activity in the hyperlipaemic plasma of
      cocks].
AB  - Two groups of cocks were kept for 84 days on a diet rich in fat (group D) or on a
      similar diet with addition of coumarin (group DK). In the plasma of these birds
      there occurred a distinct increase of the concentration of total fat (TC) and
      cholesterol (CH), in comparison with the concentration of these substances of the
      plasma of control birds. The concentration of TC in the plasma of group DK was
      higher than that observed in group D. The concentration of CH was similar in both
      experimental groups. The level of the lipolytic activity of plasma (ALpO) changed
      during the experiment and was higher in the plasma of the cocks of group DK than
      in that of group D. Confrontation of the results of the determinations of ALpO,
      TC and CH in groups D and DK demonstrates that the symptoms of a disturbance of
      the metabolism of fats, which occur in cocks kept on a diet rich in fats, are
      stimulated by coumarin. This influence is demonstrated by a speeding up, by about
      42 days, of the occurrence of these symptoms, i.e. of the increase of the TC
      concentration and of the ALpO level. The values of TC and ALpO, determined on the
      21st and 42nd day of the experiment in group DK, corresponded to the relevant
      values found in group D on the 63rd and 84th day of the experiment. It is highly
      probable that coumarin acts on the mechanisms which control the ALpO level
      indirectly, through the carbohydrate metabolism.

PMID- 16296034
TI  - [Metabolism of high-energy phosphate compounds in rabbit tissues in post
      irradiation disease].
AB  - The experiment was carried out on 40 rabbits divided in four groups. Each animal
      of the experimental groups received a 850 R dose. X-rays were applied for
      irradiation. The animals were sacrificed on the 7th, 12th and 17th day after
      irradiation. Levels of ATP/ADP and phosphocreatine were determined in the
      skeletal muscles, myocardium, liver, kidneys, blood and the mucosa of duodenum.
      On the 7th day, in all tissues a decrease of the phosphocreatine level was
      observed. The lowest level differed little from zero. Afterwards a slow increase
      of phosphocreatine concentration took place, reaching the normal level in the
      kidneys on the 17th day after irradiation. The concentration of ATP/ADP was the
      lowest on the 7th day of the experiment. A fast increase of that fraction was
      observed in the liver, where the level of ATP/ ADP on the 12th day was higher
      than in the control group. From the 12th day, a drop in the ATP/ADP level was
      observed, reaching the normal level on the 17th day. In the skeletal and heart
      muscles, after a drop on the 7th day, a slow increase of the activity was
      observed on the last day of the experiment, but the activity did not reach the
      normal level.

PMID- 16296035
TI  - [Influence of x-ray irradiation on phosphorus metabolism in rabbits].
AB  - Twenty four rabbits were used in the experiment. The animals were divided into
      four groups, 6 animals in each. The rabbits were irradiated with a total dose of
      910 R. The activity of alkaline phosphatase and the level of inorganic phosphorus
      were measured on the 5th, 10th and 15th day after irradiation in erythrocytes,
      plasma, duodenum, muscles and liver. There was found a decrease of phosphatase
      activity in the plasma, liver and duodenum, and an increase in the muscles and
      erythrocytes. The level of inorganic phosphorus increased in the duodenum, liver
      and plasma, and decreased in the muscles and erythrocytes. In the latter two, the
      increase of the phosphatase activity was accompanied by a decrease of the
      phosphorus level; on the contrary, the decrease of the enzyme activity in the
      liver and duodenum was accompanied by an increase of the phosphorus level. During
      the whole experimental period, the phosphatase activity was higher by about 40%
      than in the control group.

PMID- 16296036
TI  - [Antibiotic 26a as a factor stimulating the body growth of Japanese quails
      (Coturnix coturnix japonica)].
AB  - Groups I and II of Japanese quails were given 50 ppm of oxytetracyclin and 23 ppm
      of the antibiotic 26a in drinking water during 3 weeks, from the 7th to the 28th
      day of life. No antibiotics were given to group III. In order to determine the
      properties of the antibiotic 26a as a stimulator of growth, the mean values of
      the body weight gains in the individual groups were compared by statistical
      methods. During the 1st and 2nd weeks of the experiment, the mean body weight
      gains in group II were the highest, but in the 3rd week the highest gains were
      noted in group I. During the whole experiment, the quails in group I had an
      average gain of 63.18 g, those in group II 66,34 g, and those in group III 63,86
      g. Highly significant differences were found between the groups and between sexes
      as far as the body weight gains are concerned. The males showed smaller mean
      gains than the females, but reacted more distinctly to the stimulating action of
      the studied antibiotics.

PMID- 16296037
TI  - [Spontaneous tumours in Japanese quails].
AB  - The occurrence of spontaneous tumours in 8 female quails (C. coturnix japonica)
      aged 1.5-3 years was stated. In 7 females the adenocarcinomas of the oviduct with
      numerous metastases in the abdominal cavity were recognized. In one female the
      haemangiosarcoma arising from the pleura with few metastases in the abdominal
      cavity was found. The possibility of relation between the high productivity and
      the age of females as well as the frequency of the oviduct adenocarcinomas was
      pointed out.

PMID- 16296038
TI  - [Morphology and topography of the carotid body and carotid sinus in sheep (Ovis
      ammon f. aries L., 1758)].
AB  - The studies were conducted on 60 preparations of 30 sheep heads. The objective of
      the work was to describe the form, structure, situation, innervation and blood
      supply of the carotid body and carotid sinus in the sheep. It results from the
      present study that the carotid body of the sheep is a single formation, of an
      oval, circular or irregular shape. In most cases it lies on the surface of the
      medial termination of the common carotid artery and is situated closer to or
      farther from one of the arteries which begin in this region. The size of the body
      varies between 1.4 and 2.6 mm in diameter. The initial part of the occipital
      artery and the posteriorly adjacent dorso-lateral and medial part of the common
      carotid artery were recognized as the homologue of the carotid sinus of other
      animals. The carotid body is innervated by the carotid sinus branch of the
      glossopharyngeal nerve and by the branches of the external carotid nerves. The
      carotid sinus is innervated by the nerves described above, by a branch of the
      vagus nerve (in 50% of cases) and by a branch of the hypoglossal nerve (in 23.3%
      of cases).

PMID- 16296039
TI  - [Late results of treatment of primary tuberculosis in children].

PMID- 16296040
TI  - [Present condition of patients discharged in 1963 and 1964 with negative sputum
      and open cavern].

PMID- 16296041
TI  - [Tuberculous meningitis in infants].

PMID- 16296042
TI  - [Experiences with silicotuberculosis].

PMID- 16296043
TI  - [Organization and controled medical treatment of pulmonary tuberculosis within
      public health centers].

PMID- 16296044
TI  - [Lymph node metatasis in patients with bronchial carcinoma].

PMID- 16296045
TI  - [Pulmonary ornithosis with relapse].

PMID- 16296046
TI  - [Multilocular pulmonary echinococcosis].

PMID- 16296047
TI  - [Th 13-14 and PZA and CS in the treatment of chronic cavitary tuberculosis with
      bacterial resistance to classic antibacterial drugs].

PMID- 16296049
TI  - [Pulmonary tuberculosis].

PMID- 16296048
TI  - [Tuberculosis of the tongue in a patient with chronic pulmonary TB].

PMID- 16296050
TI  - [Clinical picture of exudative pleuritis associated with tuberculosis].

PMID- 16296051
TI  - [Surgical treatment of chronic pyothorax].

PMID- 16296052
TI  - [Causes of death in patients treated in hospital from 1945 to 1963].

PMID- 16296053
TI  - [Levels of free and acetylized PAS in the blood after the administration ALPAS].

PMID- 16296054
TI  - [The programmes for the fight against tuberculosis in its dependency from the
      epidemiological situation].

PMID- 16296056
TI  - [Cardio-respiratory syndrome in obese--Pickwickian syndrome].

PMID- 16296055
TI  - [Living and dead antituberculous vaccines].

PMID- 16296058
TI  - [Case report of surgical treatment of pulmonary plasmacytoma].

PMID- 16296057
TI  - [Role of bleeding in pulmonary aspergillosis].

PMID- 16296059
TI  - [Congratulations to Dr. Robert Neubauer on his 70 birthday].

PMID- 16296060
TI  - [Chemotherapy in patients with chronic pulmonary tuberculosis].

PMID- 16296061
TI  - [The place of the tuberculin test in modern tuberculosis control].

PMID- 16296062
TI  - [The study of the dynamic potency of tuberculosis by epidemiologic
      investigation].

PMID- 16296064
TI  - [The lessons of tuberculosis for internal medicine].

PMID- 16296063
TI  - [Chemotherapy in asymptomatic tuberculin reaction].

PMID- 16296066
TI  - [Chronic bronchitis and cigarette smoking].

PMID- 16296065
TI  - [The immunity conferred by BCG vaccination in relation to the degree of induced
      tuberculin sensitivity].

PMID- 16296067
TI  - [Comparative study of experimental tuberculosis of young and old rats].

PMID- 16296068
TI  - [Mass X-ray screening and mass BCG-vaccination in Norway].

PMID- 16296069
TI  - [Late and early diagnosis of tuberculosis situations].

PMID- 16296070
TI  - [How long to keep the patient in the hospital].

PMID- 16296071
TI  - [Methodology of planning the fight against tuberculosis].

PMID- 16296072
TI  - [Trochanter major as a substitute for the destructed head and neck of the femur
      in children--preliminary report].

PMID- 16296073
TI  - [Skin manifestations caused by the medicamentous allergy to the first
      antituberculous drugs].

PMID- 16296075
TI  - [Activities of the Tuberculosis Institute in Poland].

PMID- 16296076
TI  - [Pathogenesis of pulmonary toxomycosis].

PMID- 16296074
TI  - [Treatment of tuberculosis in Czechoslovakia].

PMID- 16296077
TI  - [Severe ulcerous intestinal tuberculosis treated with surgery in 1947].

PMID- 16296078
TI  - [Evaluation of specifity of tuberculin reactions obtained with old tuberculin and
      BCG-preparation in various children groups].

PMID- 16296079
TI  - [Value and limitations in thoracic radiography in the epidemiology of
      tuberculosis].

PMID- 16296080
TI  - [Rehabilitation in chronic respiratory insufficiency and in cardiovascular
      diseases].

PMID- 16296081
TI  - [Robert Neubauer--in gratitude].

PMID- 16296082
TI  - [Tuberculosis worldwide and in Yugoslavia].

PMID- 16296084
TI  - [The cavernostomy for far-advanced pulmonary tuberculosis].

PMID- 16296083
TI  - [The national programme of T.B. control in Ceylon].

PMID- 16296085
TI  - [Atypical mycobacteria].

PMID- 16296086
TI  - [Acute pulmonary diseases caused by Mycoplasma pneumoniae (Eaton)].

PMID- 16296087
TI  - Sensitivity to mycobacterial PPD antigens with some laboratory evidence of its
      significance.

PMID- 16296089
TI  - [Fragmentation of medical care: the price we pay].

PMID- 16296088
TI  - [Localized interlobar effusion in heart failure].

PMID- 16296090
TI  - [Occurence of primary resistance in hospital patients with respiratory
      tuberculosis].

PMID- 16296091
TI  - [Simultaneous BCG and smallpox vaccination].

PMID- 16296092
TI  - [Isolation of Mycobacterium tuberculosis from specimens of extrapulmonary
      tuberculosis].

PMID- 16296093
TI  - [Epidemiology of tuberculosis in the German Democratic Republic].

PMID- 16296094
TI  - [Antituberculosis treatment in the prevention of tuberculosis in Poland].

PMID- 16296095
TI  - [Nonuniform ventilation].

PMID- 16296097
TI  - [Technique of thoracentesis].

PMID- 16296096
TI  - [A new vaccine strain: MPH (Murine Praha Homogeneous), developed from
      Mycobacterium microti OV 247 (Wells)].

PMID- 16296098
TI  - [Additional epidemiological indices for the tuberculosis].

PMID- 16296099
TI  - [Can tuberculosis be eradicated?].

PMID- 16296100
TI  - [Professional rehabilitation in Ceylon].

PMID- 16296102
TI  - [Mild pulmonary abscesses].

PMID- 16296103
TI  - [Immediate and late complications of curette and suction interruptions of
      pregnancy].

PMID- 16296101
TI  - [Some epidemiological and clinical aspects of primary resistance to the classic
      drugs in patients with pulmonary tuberculosis].

PMID- 16296104
TI  - [Abdominal aortic aneurysms].

PMID- 16296105
TI  - [Cystosarcoma phyllodes of the breast].

PMID- 16296106
TI  - [Sequential ultrafiltration/hemodialysis for dialysis-associated ascites].

PMID- 16296107
TI  - [Selective amnesia, adjustment and the seriousness of suicide attempts].

PMID- 16296109
TI  - [Malabsorption as a presenting symptom of thyrotoxicosis].

PMID- 16296108
TI  - [Fetal trimethadione syndrome and behavior disorders in children of epilectic
      mothers].

PMID- 16296110
TI  - [Congenital pancreatic cyst in an adult].

PMID- 16296111
TI  - [Spontaneous urinary extravasation].

PMID- 16296112
TI  - [Cutis marmorata telangiectatica congenita].

PMID- 16296113
TI  - [Enkephalins and endorphins].

PMID- 16296114
TI  - [Liposome as microinjector].

PMID- 16296115
TI  - [Familial polyposis of colon].

PMID- 16296116
TI  - [Ostechondral bone grafting for articular cartilage defects].

PMID- 16296117
TI  - [Benign monoclonal gammopathy].

PMID- 16296119
TI  - [Cough in children: causes and treatment].

PMID- 16296118
TI  - [The prospects of cure for small cell lung cancer].

PMID- 16296120
TI  - [Dobutamine].

PMID- 16296121
TI  - [Progressive dyspnoe, dry cough, syncope, blood in sputum, loss of weight,
      death].

PMID- 16296122
TI  - Screening for cancer: colon, lung and skin cancers.

PMID- 16296123
TI  - Recurrent issues in the review of medical research on human subjects.

PMID- 16296124
TI  - Problems of streptococcal infection, rheumatic fever and rheumatic heart disease.

PMID- 16296125
TI  - Rheumatic fever and rheumatic heart disease in the tropics with particular
      reference to Nigeria.
AB  - This is a review of current literature on rheumatic fever and rheumatic heart
      disease in tropical and sub-tropical countries. The pattern involved in each case
      has been briefly described and compared with that in the temperate countries.
      Certain peculiarities in tropical and sub-tropical countries have been commented
      on and suggestions made for future research.

PMID- 16296126
TI  - Current status in rheumatic fever and rheumatic heart disease--an epidemiologic
      appraisal.

PMID- 16296127
TI  - Antigenic analysis of Nigerian strains of West Nile virus by neutralization test.
AB  - Employing neutralization tests, eight Nigerian strains of West Nile virus were
      investigated to determine antigenic relationships among them. One virus strain
      differed so significantly from the others and was later found to be a strain of
      Usutu virus. The other seven strains were differentiated into two serological
      intratypic groups dependent on their cross reactions with two strains which
      served as prototypes for each group. It was found that for epidemiological
      studies, screening of sera and sero-diagnosis, strain 7019 which had a broad
      spectrum of reactivity with other strains was a most suitable strain for
      detecting and evaluating antibodies to West Nile virus.

PMID- 16296128
TI  - Virological and serological studies of a suspected yellow fever virus outbreak in
      Mabudi area of Benue Plateau State of Nigeria.
AB  - Human sera collected during a suspected yellow fever outbreak in Mabudi, Benue
      Plateau State of Nigeria were examined for virus content by mouse inoculation,
      and presence of antibody by complement fixation (CF) and neutralization (N) tests
      in baby mice. No virus was isolated from 116 sera examined. 40 and 41 of the 358
      sera tested were positive for yellow fever and UgMP 359 CF antibodies
      respectively, with 12 possession CF antibodies to both viruses. In neutralization
      tests, 91 and 99 of the 243 sera tested were positive for yellow fever and UgMP
      359 N antibodies respectively with 37 positive for both viruses. Tissues from one
      hundred and twelve animals; 77 rodents and 45 birds were also tested for virus
      content and found negative. None of the 9 rodent and 3 bird sera was positive for
      N antibody to either virus.

PMID- 16296130
TI  - The effects gastrin on neuromuscular activity.
AB  - The effect of Pure Synthetic Human Gastrin-l (SHG-1) on the neuromuscular
      junction was studied using a rat phrenic nerve-hemidiaphragm preparation in an
      isolated organ bath connected to a four-channelled Physiograph recorder. It was
      found that Pure Synthetic human Gastrin-1 increased the skeletal muscular
      activity, with a mean rise of 15%/ (S.D. +/- 5.0) and N=10 x 10 for each figure.
      This action was found to be sustained for at least 60 minutes in all the
      experiments, and in this respect was different from the effect of potassium
      chloride on skeletal muscular activity. This new action of Gastrin has not been
      reported before, and further investigations are going on to elucidate the details
      of the mechanism of this action. We think that this action of gastrin will be
      found to be of great clinical significance.

PMID- 16296129
TI  - Total serum calcium and phosphorus levels in women taking oral contraceptives.
AB  - Total serum calcium and inorganic phosphorus levels were determined in 185
      Nigerian women attending the post partum Family Planning Clinic of University
      College Hospital, Ibadan, Nigeria. The concentrations of calcium and inorganic
      phosphorus were similar in 37 control subjects to those in 83 women who had been
      fitted with the Lippes loop. Serum calcium levels were significantly reduced (P <
      0.01) in 25 women taking Ovral 28 and in 40 women taking Norlestrin-Fe in
      comparison with the control group. The serum inorganic phosphorus levels were
      significantly increased (P > 0.01) in the women taking oral contraceptives in
      comparison with the control group.

PMID- 16296131
TI  - Epidemiology and prognosis of pyogenic meningitis in Nigerians--a study of 294
      patients.
AB  - The epidemiology and prognosis of pyogenic meningitis were reviewed by a study of
      294 patients of different age groups. Peculiarities in medical practice in
      African countries, where they affect the prognosis, were stressed. Age, level of
      consciousness and bacteriology are important prognostic factors. Massive health
      education campaigns, dialogues among traditional healers, pharmacists and
      orthodox clinicians in order to limit the sphere of activity of each group
      strictly to its level of competence, may help in producing a more responsible
      attitude to this disease.

PMID- 16296132
TI  - Taste sensitivity to phenylthiocarbamide in non-goitrous and goitrous Nigerians.
AB  - Taste sensitivity to phenylthiocarbamide is thought to reflect a genotype
      homozygous for a single recessive gene. European and North American populations
      show a mean non-taster frequency of about 30% whereas Mongoloid populations show
      a much lower frequency of non-tasters. In the present study of Nigerians, there
      were mean non-taster frequencies of 1.9-2.9% among healthy subjects and not a
      significantly different level, 3.5%, among goitrous ones. Among subjects with
      nodular goiter, however, the non-taster frequency was 18.7%, significantly
      higher. The results suggest that there is a rarity of non-tasters among Nigerians
      and that non-tasters are more susceptible to the development of nodular goiter
      than are tasters.

PMID- 16296133
TI  - Amniotic fluid bilirubin and creatinine concentrations in Nigerian pregnant
      women.
AB  - Amniotic fluid bilirubin and creatinine levels were determined in 143 pregnant
      patients of known maturity. The bilirubin values did not bear any significant
      relationship with the gestational age. The creatinine levels however, showed a
      rise as pregnancy progressed. Amiotic fluid mean creatinine values were below 1
      mg/100 ml before 30 weeks and around 2 mg/100 ml close to term. Eighty per cent
      of all creatinine values at 37 weeks gestation and over were 1.6 mg/100 ml or
      more. The mean level of creatinine in amniotic fluid correlated with gestational
      age. This test can therefore be applied antenatally along with other clinical
      data to distinguish between the premature and mature infants.

PMID- 16296134
TI  - Evolution of ureteroileocutaneous anastomosis--a review.
AB  - The experience with uretero-ileo-cutaneous anastomosis since it was introduced by
      Bricker in 1950 has been reviewed. Emphasis has been placed on modifications that
      have been employed to reduce the complications of this procedure. The current
      status of this operation is outlined.

PMID- 16296135
TI  - Management of conductive deafness of non-suppurative aetiology in Nigeria.
AB  - A review of 39 cases of deafness of non-suppurative aetiology seen in the
      Department of Otolaryngology of the University College Hospital, Ibadan between
      1966 and 1971 is presented. Deafness of this type is not as common as deafness of
      suppurative origin but it presents problems of its own. First there is the
      inability of many patients to give accurate histories and describe actual
      sensation in the ear. Secondly, there is the problem created by patients not
      turning up for regular follow up. Thirdly, there is the problem of unavailability
      of necessary equipment such as that highlighted by the use of straight polythene
      tubes instead of the shaped grommet in the management of serous otitis media and
      the non-availability of prosthesis to replace the stapes when stapedectomy may
      have helped the patients. Suggestions are also offered on the ways of improving
      the treatment of the patients.

PMID- 16296136
TI  - Diagnosis of non-functioning primary ovarian carcinoma.
AB  - A review of the clinical diagnosis of non-functioning primary ovarian carcinoma
      has been carried out from the records of a Teaching Hospital in London and from
      the Lagos University Teaching Hospital, Lagos and the observation from these two
      centres have been compared with those from the Mayo Clinic.

PMID- 16296137
TI  - Retinal diseases in Nigerians--a preliminary report.
AB  - Of 595 new patients seen in the Eye Clinic of Lagos University Teaching Hospital,
      twenty-seven had retinal diseases, a prevalence of 4.5% Seven of these patients
      had retinopathy associated with sickle cell haemoglobinopathy and another seven
      had macular degenerations. Other causes of retinal diseases are analysed and the
      findings compared with reports from other countries. It is suggested that
      haemoglobin electrophoretic fractionation should be done in young Nigerians
      presenting with retinal diseases.

PMID- 16296138
TI  - Observations on abdominal injuries in the Nigerian Civil War.
AB  - A retrospective study of 331 patients who sustained abdominal injuries during the
      Nigerian Civil War 1967-70 and were treated at Base Surgical Centres in the 3
      Field Ambulance Nigerian Army is made. The most commonly injured organs are small
      intestine 148, caecum and colon 80, liver 69, spleen 26, stomach 28 and kidney
      24. Case fatality rate is 33.8%. Factors influencing case mortality rate include
      type of organ injured, number of organs hit by penetrating missile, peri
      operative complication. Other factors, not measurable in this study are
      mentioned. The few patients with injuries severally to the pancreas or the gall
      bladder who reached the operating table alive, all showed injuries to some other
      organs; these are among those with the highest mortality rates. Comparisons are
      made with similar studies from the Second World War 1942-45 and the Korean War
      1952-53.

PMID- 16296139
TI  - Immunity and allergy--a report of skin-testing (for allergic diatheses) in
      Nigeria.
AB  - The importance of Allergy in the causation of several important diseases e.g.
      Asthma, is well known (Voohorst 1962; Voorhorst, Spieska-Beezeman and Spieska
      1964-). In this article, the value of finding out the causative allergen by a
      detailed case-history and later by a skin-testing against the most probable
      allergens (as suggested by the case-history)--is stressed. The major allergens
      responsible for the Allergic immunopathies in Nigeria--as found by testing in 50
      cases are mentioned. It is hoped that more hospitals will be stimulated to
      perform skin-testing in view of the encouraging results and responses to de
      sensitization so far obtained in different centres practising this procedure.

PMID- 16296140
TI  - Acquired gynaetresia in Ibadan.
AB  - Acquired atresia of the vagina is much less common than the congenital type, but
      more frequent in the tropics than in the developed countries (Lawson and Stewart,
      1967). This is because most of the causes which include chemical vaginitis
      (Frith, 1960), female circumcision (Mustafa, 1966) and birth injuries (Lawson and
      Stewart, 1967) are largely confined to the tropics, due to poverty, ignorance and
      lack of good medical facilities. In the developed parts of the world, acquired
      gynatresia is rare, and perhaps follow mainly colporrhaphies and intra-vaginal
      irradiation from treatment of pelvic malignancies, (Patterson and Rhodes 1958,
      Whitely, 1964). In Ibadan, Nigeria, however, by far the commonest cause of
      vaginal atresia is chemical vaginitis from vaginal insertion of local caustic
      pessaries, for the treatment of certain gynaecological problems. This paper is,
      therefore, designed to highlight the clinical presentation of acquired
      gynaetresia as seen in Ibadan with particular emphasis on its incidence,
      causation, symptomatology and operative management.

PMID- 16296142
TI  - Primary carcinoma of the fallopian tube in a Nigerian.
AB  - The first documented report of a rare neoplasm, primary carcinoma of the
      fallopian tube in a postmenopausal Nigerian is presented. The patient complained
      of postmenopausal bleeding which persisted after curettage and satisfactory
      treatment of a pre-existing senile vaginitis and cervicitis. The diagnosis of
      tubal carcinoma was made only at the time of exploratory laparotomy at which a
      total hysterectomy and bilateral salpingo-oophorectomy was performed and
      confirmed at histopathological examination of the specimen. Problems relating to
      its unusual symptomatology, its association with pelvic inflammatory disease and
      pelvic tuberculosis, diagnostic difficulties, choice of treatment and factors
      that may influence survival are discussed.

PMID- 16296141
TI  - Caesarean section and maternal mortality at the Lagos University Teaching
      Hospital.
AB  - There were sixteen maternal deaths following 1,450 Caesarian sections at the
      Lagos University Teaching Hospital in an eight year period 1966 to 1974, a
      maternal mortality rate of 1.1%. The chief causes of maternal deaths in this
      environment are pre-eclamptic toxaemia, eclampsia and haemorrhage. Most of the
      obstetric deaths following Caesarian sections are preventable through the
      application of current knowledge and availability of modern facilities. Reduction
      of maternal deaths will follow recognition and attention to the most frequent
      causes.

PMID- 16296143
TI  - Fatal coital rupture of pouch of Douglas.
AB  - One fatal case of coital rupture of pouch of Douglas is reported. Three other
      nonfatal cases are mentioned. They were seen in a rural practice soon after the
      Nigerian civil war. Nutritional deficiencies common in the area at the time are
      thought to have contributed to their occurrence.

PMID- 16296144
TI  - Acute idiopathic volvulus of the stomach.
AB  - A report is made of the occurrence of acute idiopathic volvulus of the stomach in
      a 65 year old Nigerian male patient. To our knowledge, this is the first reported
      case of this rare condition in a Nigerian. The classification, diagnosis and
      surgical management of gastric volvulus are discussed and the world literature on
      this condition reviewed.

PMID- 16296145
TI  - Ameloblastic fibroma--a case report.
AB  - A case of ameloblastic fibroma in a female Nigerian child aged 4 years is
      reported. The case is shown to present the main clinical and histological
      features described in similar cases. Two unusual findings are emphasised, namely
      the radiographical appearance of multilocular rather than the usual unilocular
      radiolucency and the great extent of bone erosion. Thorough curettage is
      advocated as the treatment of choice and careful follow-up is recommended.

PMID- 16296146
TI  - Hysterosalpingogram carried out inadvertently in very early pregnancy--case
      report.
AB  - A patient inadvertently exposed to bysterosalpingogram at five weeks amenorrhoea
      (gestation) is reported. While utmost care should be exercised to avoid this type
      of exposure the reported case has up to four years follow-up not developed any
      symptoms of adverse effects.

PMID- 16296147
TI  - Difficulties facing a government hospital medical officer in writing medical
      papers.
AB  - Government Hospitals not involved with medical schools often lack the full
      facilities of the paramedical sector. Therefore the medical officers are faced
      with this difficulty when attempting to write medical papers. The government
      should try to improve this so as to raise the interest of all concerned in
      reporting interesting cases.

PMID- 16296148
TI  - Experiences with blood substitutes.

PMID- 16296149
TI  - Coffee and your blood pressure.

PMID- 16296150
TI  - [Nature is not without side effects].

PMID- 16296151
TI  - [Pathomechanisms of the elicitation phase of allergic contact dermatitis].
AB  - Allergic contact dermatitis (ACD) is a T-cell mediated, antigen-specific
      inflammatory response to repeated epicutaneous exposure to haptens. Two
      immunologically distinct sequential steps are required to produce the clinical
      picture of ACD. In the sensitization phase, naive antigen-specific T cells are
      primed and differentiate into memory or effector T cells. In the elicitation
      phase, reapplication of the same hapten leads to local recruitment of hapten
      specific T cells which are cytotoxic, release cytokines and recruit other
      inflammatory cells. These events lead to clinically visible tissue inflammation
      characterized by edema, erythema, scaling, and blistering. For the clinician, the
      effector phase is especially important, because sensitization is generally
      asymptomatic, whereas elicitation produces the clinical picture of ACD. Detailed
      knowledge about the mechanisms of the elicitation phase of ACD is needed in order
      to develop novel therapeutic approaches.

PMID- 16296152
TI  - [The role of biologics into the management of psoriasis: a consensus paper by the
      Psoriasis Study Group, Arbeitsgemeinschaft Dermatologische Forschung].
AB  - About 20% of all psoriasis patients require photo- and/or systemic therapy
      because of the severity of their disease. Side effects, contraindications,
      insufficient clinical responses, and lack of long-term efficacy underline the
      need for novel and improved anti-psoriatic therapies. In recent years, the
      technology has been established to generate therapeutic molecules from living
      cells capable of inhibiting disease-relevant mediators or cell-cell interactions.
      Several of these so-called biologics interfering with key steps in the
      immunopathogenesis of psoriasis have the potential to meet this need with regard
      to treating moderate to severe psoriasis. Here, the Psoriasis Study Group of the
      Arbeitsgemeinschaft Dermatologische Forschung (ADF) analyses the established anti
      psoriatic treatment modalities. With the shortcomings of these options in mind,
      biologics with an immediate relevance for clinical application in the treatment
      of psoriasis are discussed. The focus is on their potential medical advantages
      along with safety aspects. Moreover, legal and economical aspects with an impact
      on the use of biologics are addressed.

PMID- 16296153
TI  - [Sensitization to tea tree oil in Germany and Austria. A multicenter study of the
      German Contact Dermatitis Group].
AB  - BACKGROUND AND AIM: Tea tree oil, a distillation product of the Australian tea
      tree (Melalence alternitolia) is increasingly used as an alternative remedy for
      various dermatological diseases. Tea tree oil contains several allergenic
      monoterpenes and sesquiterpenes. In this multicenter study it was evaluated,
      whether the increasing use of tea tree oil has lead to an increased frequency of
      sensitization in Germany and Austria which would justify its inclusion into the
      standard series. PATIENTS AND METHOD: For patch testing a standardized tea tree
      oil was used, dissolved 5% in diethylphtalate (DEP). Consecutive patients of 11
      dermatological departments in Germany and Austria were tested. Readings were
      taken on day 2 and 3 according to the guidelines of the German Contact Dermatitis
      Research Group (DKG). RESULTS: 5% tea tree oil was positive in 36/3375 patients
      (1.1%). Sensitization frequencies showed great regional variations and ranged
      from 2.3% (Dortmund), 1.7% (Buxtehude), 1.1% (Essen), 0.7% (Graz), to 0% (Berlin,
      Vienna). 14/36 patients (38.9%) also showed a positive patch test reaction to oil
      of turpentine. CONCLUSION: Our results show that tea tree oil is an important
      contact allergen for some centers. It should be tested, if medical history
      suggests its previous use. Considering the great regional differences in
      frequencies of sensitization its inclusion into the standard series is not
      recommended yet.

PMID- 16296154
TI  - Efficacy of superficial and deep regional hyperthermia combined with systemic
      chemotherapy and radiotherapy in metastatic melanoma.
AB  - BACKGROUND AND OBJECTIVE: Response rates of cutaneous-subcutaneous or lymph node
      metastases of melanoma to systemic chemotherapy are rather low. We report our
      clinical experience with superficial and deep regional hyperthermia in
      combination with radiotherapy and/or chemotherapy with carboplatin.
      PATIENTS/METHODS: We treated 15 patients with metastatic melanoma (6 men, 9
      women; age 39-84 years, mean age 60 years) by using superficial or deep regional
      hyperthermia produced by electromagnetic energy. Superficial hyperthermia was
      delivered to skin or lymph node metastases in combination with radiochemotherapy
      in 12 patients, while deep regional hyperthermia was administered with an annular
      array applicator to lymph node metastases either in combination with
      radiochemotherapy (1 patient) or with carboplatin alone (2 patients). The
      clinical response was assessed by clinical evaluation and/or computer tomography
      and/or ultrasonography at monthly intervals. RESULTS: Both superficial and deep
      regional hyperthermia was well tolerated. We observed 5 complete local remissions
      (34%), 6 partial local remissions (40%) and 2 patients with stable disease (13%).
      The best results were obtained in cutaneous or retroperitoneal metastases.
      CONCLUSIONS: Local response can be achieved in inoperable metastatic melanoma
      using superficial or deep regional hyperthermia in combination with
      radiochemotherapy or chemotherapy.

PMID- 16296155
TI  - [Graft-versus-host-like flexural eruption after autologous stem cell
      transplantation].
AB  - A 29-year-old man received an autologous stem cell transplantation after
      myeloablation with busulfan and cyclophosphamide to treat his acute myeloid
      leukemia, a. Five days after retransfusion of stem cells, hyperpigmented, scaly
      lesions with occasional perpheral lichenoid papules developed in groins, axillae,
      genitalia, and elbows. Histology revealed a graft-versus-host-like reaction.
      Although the graft-versus-host reaction, by definition, requires allogeneic
      cells, similar lesions have been reported after autologous stem cell
      transplantation. The clinical course is usually mild and self-limited. Flexural
      graft-versus-host-like reactions after autologous stem cell transplantation have
      been reported in four patients.

PMID- 16296156
TI  - [Predilection sites of the skin].

PMID- 16296157
TI  - [Diagnosis and therapy of urticaria].

PMID- 16296158
TI  - [Presentation of the Schaudinn-Hoffman Plaque to professor Wilhelm Meigel].

PMID- 16296159
TI  - [HPV7-induced cutaneous warts in butchers: a professional disease?].

PMID- 16296160
TI  - Amelanotic/hypomelanotic melanoma--is dermatoscopy useful for diagnosis?

PMID- 16296161
TI  - Botox and the prostate: a new wrinkle.

PMID- 16296162
TI  - Patterns of in vivo lymphoid responses to tumour specific antigens.
AB  - A tumour-derived antigen complex injected induced a different cellular immune
      response in tumour-bearing mice when compared with unprimed controls. A different
      statistical approach, namely the linear correlation, allowed us to discern
      significant differences in the response pattern.

PMID- 16296163
TI  - Na+ dependence of phenacetin absorption.
AB  - Phenacetin in solution at different concentrations of Na+ was orally administered
      to dogs. Phenacetin absorption is increased by the Na+: a positive correlation
      was noted between the Na+ concentration in the medium and the plasma levels of
      phenacetin. Ouabain antagonizes the effect of Na+ on phenacetin absorption.

PMID- 16296164
TI  - A tumor-cell-agglutinating lectin in snail mucus from Arion lusitanicus (MAB) and
      Arion empiricorum (Fer.).
AB  - A lectin which agglutinates Zajdela hepatoma cells; rat red cells and
      lymphocytes, but no normal rat liver cells, was detected in the mucus, yielded by
      simple saline extraction, of the two snail species Arion empiricorum (Fer.) and
      Arion lusitanicus (MAB). The agglutination spectrum involves also human
      erythrocytes and red cells of several animal species.

PMID- 16296165
TI  - Uptake of labeled mammalian gonadotropins by ovary and oviduct of the lizard,
      Lacerta s. sicula, in vivo.
AB  - The uptake of radioactivity by ovary, oviduct and thigh muscles of the lizard,
      Lacerta s. sicula, after administration of labeled mammalian gonadotropins has
      been followed. Ovary and oviduct show a significantly higher radioactivity than
      thigh muscles. The ovarian uptake, moreover, is decreased by the corresponding
      non-labeled gonadotropin. The meaning of these observations for the physiological
      regulation of reproductive processes in that lizard, are discussed.

PMID- 16296166
TI  - Changes in the haemolymph protein pattern during ovarian maturation in Xylocopa
      litipes.
AB  - The haemolymph proteins of a hymenopteran insect Xylocopa litipes have been
      fractioned by the polyacrylamide gel disc electrophoresis. The haemolymph protein
      fractions have been examined histochemically. The changes taking place in the
      haemolymph protein pattern during vitellogenesis have been studied. Common
      protein fractions were observed in the haemolymph, fat body, ovary and testis.
      The role of sex specific protein during the vitellogenesis has been discussed.

PMID- 16296167
TI  - Apparent electric charge of protein molecules. Human thyroxine - binding
      proteins.
AB  - 1. By comparison of electrophoretic mobilities of two different charged particles
      under the same conditions the net elementary electrostatic charge of one particle
      could be calculated when the charge of the other is known. 2. The electrophoretic
      mobility of human thyroxine - binding globulin does not depend upon the
      concentration of Tris - HCl buffer in the range 0.05 to 0.20 molar. The value of
      this mobility is 0.078 and 0.083 cm2 vol(-1) hour(-1) at pH 7.0 and 8.6,
      respectively. 3. The net elementary electrostatic charge of the human thyroxine -
      binding globulin appears to be approximately 22 negative elementary electrostatic
      units in mild alkaline solutions.

PMID- 16296168
TI  - Effect of p-nitro-substitution on the metabolism of benzoic acid in the Indian
      fruit bat.
AB  - The introduction of a nitro-group at the 4-position of benzoic acid does not
      alter remarkably the metabolic pattern of benzoic acids in the fruit bat. It is
      shown here that the Indian fruit bat does not form hippuric acid with nitro
      benzoic acid, the main conjugate being the glucuronide in addition to other
      conjugates suspected to be p-amino benzoylglutamic acid and p-nitro
      benzoylglutamic acid respectively. More unmetabolized nitrobenzoic acid is
      present in the 24hr. urine than reported for unsubstituted benzoic acid. The
      Indian fruit bat exhibits an appreciable ability to reduce the nitrogroup in
      nitrobenzoic acid to the amino compound and to acetylate the amino group to the
      acetamido compound.

PMID- 16296169
TI  - Protein determination: a comparison of several methods.
AB  - A comparison of four methods for the determination of total proteins is presented
      from the following points of view: - sensitivity; - specificity; - amount of
      work, chemicals, time and equipment needed for the performance of the
      determination. The following tests have been examined; Tombs' (absorbancy at 210
      nm); Waddell's (difference in absorbancy between 215 and 225 nm); Warburg's
      (absorbancy at 280 nm); Lowry's (absorbancy at 500 nm after the reaction with
      phenol reagent). The authors recommend Tombs' method for its outstanding
      sensitivity, specificity and simplicity as the best of the four.

PMID- 16296170
TI  - Effect of biotin on DNA and histone phosphorylation in the rat liver.
AB  - The results offer further evidence for biotin activity in the phosphorylation
      mechanism. The decreased 32p incorporation into DNA and histones found in the
      biotin deficient rat liver is indicative of the importance of the vitamin in the
      DNA and histones synthesis and in the interactions between histone proteins and
      DNA, and consequently on the RNA and proteins synthesis.

PMID- 16296171
TI  - Studies on biosynthesis of sterol/steroid from dopamine.
AB  - The in vitro incubation of the anterior kidney, posterior kidney, liver, brain,
      spleen and ovarian tissue homogenates of the fish Nandus nandus with DOPA has
      been studied with regards to cholesterol production. All tissues except liver
      give highly positive results. There is also an increase in the neutral 17
      ketosteroids. Injections of Dopamine also produce similar results. It is then
      concluded that DOPA and Dopamine are important precursors of cholesterol in the
      fish tissues.

PMID- 16296172
TI  - Protein and lipid concentration in the haemolymph of Danais chrysippus. Linn.
AB  - Proteins and lipids in the haemolymph in both the sexes of the Danais chrysippus
      has been observed during the first gonotropic cycle. The concentration
      fluctuations in these haemolymph metabolites are correlated with the
      physiological state of the insect. The total protein and lipid concentration in
      the haemolymph of unmated females have been found to be low than the
      concentration found for the normal females although it followed the same type of
      oscillations in the concentration as have been observed for normal females.

PMID- 16296173
TI  - Changes taking place in the electrophoretic haemolymph protein pattern during
      metamorphosis of Polytela gloriosae (Lepidoptera).
AB  - The haemolymph proteins of the larva, pupa and adult of Polytela gloriosae have
      been fractioned by Polyacrylamide gel disc electrophoresis. In the haemolymph of
      the fifth instar larval stage a total of ten protein fractions have been
      detected. The concentration of the protein fractions 2, 3, 4, 9 and 10 shows
      oscillations in their concentration in the early fifth instar, middle fifth
      instar and late fifth instar larval stage. In all 11 protein fractionswere
      detected in the haemolymph of different stages of the pupa. The protein bands 1,
      7 and 10 of the pupa appear newly in the haemolymph as these bands were not found
      in the haemolymph of the larvae. The protein fraction 9 of larva was not found in
      the pupa. In the haemolymph of adult insect sexual difference was observed in the
      haemolymph protein pattern. In the haemolymph of adult female a total of 10
      protein fractions were detected while from the male haemolymph a total of 8
      protein fractions were detected. The pupal band 7 was not found in the adults of
      both the sexes. In the haemolymph of larva and adult one pigmented protein
      fraction was observed. No pigmented protein fraction was found in the haemolymph
      of pupa. Iron - containing protein fraction and the acid mucopolysaccharides were
      not found in the haemolymph. The protein fractions 3, 4, 5, 6 and 7 of adult
      haemolymph were darkly stained by the Schiff reagent and, thus, they are the
      fractions of glycoprotein. One protein fraction of lipoprotein was also found in
      the haemolymph.

PMID- 16296174
TI  - Automated colorimetric method for the determination of serum gamma-glutamyl
      transpeptidase utilizing the Technicon SMAC alkaline phosphatase flow channel.
AB  - An automated procedure for the determination of serum gamma
      glutamyltranspeptidase using Technicon SMAC alkaline phosphatase flow channel has
      been developed. The flow variants are insignificant. We use L-gamma-glutamyl-3
      carboxy-4-nitroanilide as a very soluble substrate. With the dyalisis procedure,
      hemoglobin and bilirubin do not interfere. By employing dialysis, the need of
      blank corrections is therefore eliminated. The procedure can been run at 130
      determinations per hour with insignificant carryover and satisfactory precision.

PMID- 16296175
TI  - In vitro and in vivo observations on the erythrocyte uptake of 17
      monochloroacetylajmaline.
AB  - The in vitro and in vivo observations on the uptake rate of 17
      monochloroacetylajmaline by human erythrocytes showed that about 30-35% of the
      drug is bound to red blood cells. These findings suggest a peculiar affinity of
      the drug for the erythrocytes, may be for the membrane or stromal phospholipids.

PMID- 16296176
TI  - The effect of vasotocin on plasma glucose, free fatty acids and growth hormone in
      the frog, Rana catesbeiana.
AB  - Injections of arginine vasotocin into bullfrogs had no effect on plasma glucose
      after 30 min. but caused hyperplycemia after 120 min. Plasma levels of growth
      hormone were elevated earlier (30 min.) and returned to control levels after 120
      min. Plasma free fatty acids were unaltered following vasotocin administration.
      It is suggested that the hyperglycemic effect of vasotocin may be mediated via
      growth hormone.

PMID- 16296177
TI  - The effect of ricin on the parathyroid gland.
AB  - On the basis of the performed experiments it seems that under the influence of
      ricin there is a parathyroid hyperactivity in the organism.

PMID- 16296178
TI  - Determination of proteins in unconcentrated normal human urine.
AB  - The protein content of repeatedly dialyzed urine is determined by measuring its
      absorbancy at 210 nm.

PMID- 16296179
TI  - Studies on the cholesterol synthesis in the human adipose tissue: I - effects of
      amino acids and ascorbic acid.
AB  - Incubation of various amino acids in glucose-saline-ascorbic acid medium with
      human adipose tissue homogenates gives very high cholesterol values. Ascorbic
      acid thus is an important factor in cholesterol synthesis as well as in general
      metabolic shifts from pyruvic acid and acetyl CoA.

PMID- 16296180
TI  - On call. My wife's doctor always tells her to fast before he checks her
      cholesterol so he can measure her triglycerides, but my doctor says triglycerides
      don't matter. Who is right?

PMID- 16296181
TI  - Working together.

PMID- 16296182
TI  - New legislative agenda includes limited focus on health issues.

PMID- 16296183
TI  - Independent review: an opportunity to improve the medical care system.

PMID- 16296184
TI  - Disease management in Medicaid plans: moving health care into the patient's
      world.

PMID- 16296185
TI  - Partnering to improve Medicaid access and quality.

PMID- 16296186
TI  - The role of genetics in managed care: seeking ways to better incorporate genetics
      into regular practice.

PMID- 16296187
TI  - The Breast Cancer Research Stamp: sticking with a great idea.

PMID- 16296188
TI  - Paying for cybercare?

PMID- 16296189
TI  - When the nation hurts: behavioral health care enters a new era.

PMID- 16296191
TI  - Health plan guide to clinical trials: outlining the issues.

PMID- 16296190
TI  - Getting the message out: eye exams save sight.

PMID- 16296192
TI  - Preventing unintended pregnancy: a role for health plans.

PMID- 16296193
TI  - Keeping health plans ahead of the curve.

PMID- 16296195
TI  - WVSMA's Healthcare Summit 2005. Inaugural address: keeping the promise.

PMID- 16296194
TI  - A primer of E-health terms.

PMID- 16296196
TI  - WVSMA's Healthcare Summit 2005. Presidential address: building on a record of
      success: together we are stronger.

PMID- 16296197
TI  - Assessing physician access under West Virginia Workers' Compensation.

PMID- 16296198
TI  - Monotherapeutic brachytherapy for clinically organ-confined prostate cancer.
AB  - Since the mid-1980s, permanent prostate brachytherapy has been utilized
      increasingly as a potentially curative treatment for patients of all ages with
      clinically localized prostate cancer To determine the 8-year biochemical
      progression-free survival rate for patients who had undergone monotherapeutic
      brachytherapy for clinically organ-confined prostate cancer, we conducted a study
      of 202 patients at Schiffler Cancer Center at Wheeling Hospital in Wheeling,
      W.Va. These patients had undergone brachytherapy without supplemental external
      beam radiation therapy or androgen deprivation therapy for clinical T1b-T2c NxM0
      (2002 AJCC) prostate cancer from April 1995 through May 2001. No patient
      underwent seminal vesicle biopsy or pathologic lymph node staging. The median
      follow-up was 5.2 years. All patients underwent brachytherapy more than 3 years
      prior to analysis. Biochemical success was defined as a PSA < 0.4 ng/mL after a
      nadir. Clinical, treatment and dosimetric parameters evaluated for biochemical
      progression-free survival included patient age, clinical T-stage, Gleason score,
      pretreatment PSA, risk group, percent positive biopsies, isotope, prostate
      volume, brachytherapy planning volume, V100/150/200, D90, tobacco status,
      hypertension and diabetes. For the entire group, 8-year biochemical progression
      free survival was 97.4% for Pd-103 and 93.3% for I-125. The median post-treatment
      PSA for the entire group was < 0.1 ng/mL. In multivariate analysis, only
      pretreatment PSA predicted biochemical outcome with a trend for better outcome
      with younger patient age and lesser percent positive biopsies. The results of our
      study indicate that permanent interstitial brachytherapy as a monotherapeutic
      approach for patients with clinically organ-confined disease results in a high
      probability of 8-year biochemical progression-free survival with a median PSA <
      0.1 ng/mL. Generous periprostatic treatment margins with documented high quality
      day 0 postoperative dosimetry are mandatory for such outcomes.

PMID- 16296200
TI  - Paratubal cyst: a case report.
AB  - Paratubal cyst can undergo torsion that can make it difficult to diagnose since
      tubal cysts mimic ovarian cysts. Most reported cases of paratubal cysts have
      occurred in pediatric patients, and this type of cyst rarely causes symptoms of
      lower abdominal pain mimicking appendicitis. We present the case of a 28-year-old
      female who was taking Carbergoline for hyperprolactinoma associated with a
      pituitary adenoma who came to the ER at Henry Ford Hospital in Detroit
      experiencing severe abdominal pain. Her pain was not accompanied by nausea,
      vomiting or other gastrointestinal symptoms. A transvaginal ultrasound revealed a
      normal uterus with the right ovary containing a cyst measuring 3 cm. x 2 cm. She
      was released on analgesics and seen at the clinic at Henry Ford Hospital three
      days later. She was still experiencing pain and was given antibiotics and
      Darvocet. When the pain had not subsided 48 hours later, a decision was made to
      perform diagnostic laparoscopy. Surgery was performed 10 days later and a
      paratubal cyst was removed that was twisted twice on its pedicle. This case
      illustrates the fact that torsion of paratubal cyst should be included in the
      differential diagnosis of adnexal pain.

PMID- 16296199
TI  - Diagnostic pitfall of computed tomography in patients with superficial siderosis
      of the central nervous system.
AB  - Superficial siderosis of the central nervous system (SSCN) is a well-described
      entity with distinct clinical presentation as well as computed tomography (CT)
      and magnetic resonance imaging (MRI) findings. However, it is critical that when
      a patient previously diagnosed with SSCN undergoes CT on the brain at a later
      date, that this scan not be misinterpreted as a new subarachnoid hemorrhage (SAH)
      so unecessary repeated angiograms are not performed. This report describes such a
      situation and discusses unique CT findings in SSCN that have been under
      recognized and under-emphasized. While conditions such as SAH should not be ruled
      out, they would be considered atypical. Combined with an adequate prior
      diagnostic testing history, physicians should proceed to MRI without subjecting
      the patient to repeat angiography.

PMID- 16296201
TI  - Influenza and influenza-like illness: information for physicians and other health
      care providers.

PMID- 16296202
TI  - Fast medicine.

PMID- 16296204
TI  - Hemophilic pseudotumor.
AB  - Bleeding diatheses are a hallmark of hemophilia. Hemophilic pseudotumor results
      from multiple episodes of hemorrhage into bones or soft tissue spaces. It is
      uncommon and is seen in severe cases of hemophilia only 1-2% of the time.
      Complications and symptoms arise due to pain and/or compression of surrounding
      structures. Pathologic fractures can be associated with intraosseous lesions and
      can result from bone destruction or resorption due to the chronic pressure of an
      osseous hemorrhage. Radiographs may demonstrate expansile lesions of the bones or
      increased soft tissue density that may be associated with extra osseous lesions.
      Bleeding may also occur within the joint space. These intra-articular hemorrhages
      can, over time, result in hemophilic arthropathy. The following case report
      demonstrates both an expansile lesion of a metacarpal as well as hemophilic knee
      arthropathy in an 11 year old.

PMID- 16296205
TI  - When is it appropriate to bill physician services using modifier -59?
AB  - Accurate coding of medical services is a constant challenge for physicians and
      could jeopardize a practice if not taken seriously. Insurance carriers use
      sophisticated claims-processing software that easily identifies coding trends by
      physicians and flags outliers within specialties. The Office of Inspector General
      (OIG) and the Center for Medicare and Medicaid Services (CMS) hire auditors to
      identify areas for review which are commonly miscoded. One area that has been
      flagged for review is billing with modifier -59 because misuse of this modifier
      has increased inappropriate reimbursement. Be cautious when using this modifier,
      due to the legal and compliance ramifications when documentation does not
      adequately support the "distinct procedural service" to justify the use of
      modifier -59.

PMID- 16296206
TI  - Living in the moment.
AB  - In a society that is probably the most fast-paced and frenetic society on earth,
      the practice of medicine is arguably among the most hectic professions. For many
      physicians, patient loads are increasing and hours are growing longer. Less time
      is being spent with patients because more time must be spent hassling with
      business matters and dealing with third-party payors. Our work lives are
      scheduled and then overscheduled, leaving less time and energy for personal
      lives.

PMID- 16296207
TI  - Highlights of the Medicare Prescription Drug Act.

PMID- 16296208
TI  - Liability surcharges in physician offices.

PMID- 16296209
TI  - OSMA and Oklahoma medicine: 1956-1965.

PMID- 16296211
TI  - Patient Page #64. The do's and dont's of taking prescription medications.

PMID- 16296210
TI  - Spirituality as a factor in health care.

PMID- 16296213
TI  - Progress and pitfalls in underrepresented minority recruitment: perspectives from
      the medical schools.
AB  - PURPOSE: To assess current initiatives at U.S. medical schools to recruit
      underrepresented minorities (URM) and to identify perceived barriers to
      enrollment of URM students. METHODS: We developed a survey that was mailed to the
      dean of Student Affairs of all U.S. allopathic and osteopathic medical schools in
      2002. Respondents were asked to list their schools' URM recruitment programs and
      rate the effectiveness of these programs. They were also asked to indicate
      barriers to URM recruitment from a list of 37 potential barriers and rate their
      overall success with URM recruitment. RESULTS: The study had a 59% response rate.
      All schools reported a wide variety of initiatives for URM recruitment with > or
      =50% of all schools using each of the 11 strategies. The three most commonly
      listed barriers to URM recruitment were MCAT scores of applicants (90%), lack of
      minority faculty (71%) and lack of minority role models (71%). Most schools rated
      their recruitment efforts highly; on a scale of 1 to 10 (10 being very
      successful), the average score was an 8. CONCLUSION: While schools continue to
      invest tremendous efforts in recruiting minority applicants, admissions criteria,
      lack of URM faculty and the need for external evaluation remain important
      barriers to achieving a diverse physician workforce.

PMID- 16296214
TI  - A century after Flexner: the need for reform in medical education from college
      and medical school through residency training.
AB  - The last major change in medical education occurred almost 100 years ago
      following an independent investigation conducted by Dr. Abraham Flexner in 1910.
      Although individual institutions have implemented drastic changes in their own
      curriculum and the accrediting agencies have mandated other initiatives intended
      to maintain medical education at the cutting edge of science and technology, many
      facets of medical education, from the premedical requirements through medical
      school and residency training, have not changed in nearly half a century. There
      are areas that are completely lacking in the process of training physicians, and
      perhaps the assumption was that physicians were intelligent enough to figure this
      out on their own. While that may have been true in the past when things were less
      complicated, this approach offers too many opportunities for misadventure,
      ultimately to the detriment of physicians and patients. Perhaps what is needed is
      a more rigorous, didactic training program and more thought put into areas where
      judgment, morality and ethics converge to create potential hazards that can
      defeat the finest training, equipment and intent. Although American residency
      programs produce physicians fully capable of independent practice after their
      prescribed periods of training, there are elements of these training programs
      that are outdated, costly and perhaps not the best way to get to the desired
      endpoint. Perhaps these can be revised to more accurately reflect the changing
      times. This manuscript addresses some of these issues at all levels of training
      with recommendations for corrective action.

PMID- 16296215
TI  - An analysis of the association of American medical colleges' review of minorities
      in medical education.
AB  - The Association of American Medical Colleges publishes an enormous database each
      year, which encompasses every conceivable category of medical education. This
      information covers high-school student premedical activities, medical
      school/student data, demographics of residents and fellows in training, a profile
      of medical school faculty according to academic rank and the enrollment of each
      medical school in the country. It is all categorized according to race, ethnicity
      and gender. Furthermore, it is a longitudinal survey and, therefore, valid
      comparisons can be made over long periods of time. The extensive coverage of
      African-American involvement in the system at all levels allows for healthcare
      planners, administrators, politicians and students/parents at all levels to use
      this as a roadmap for planning purposes. Much of the data is broken down
      according to individual states, thus enabling students to make better decisions
      about selecting private versus public institutions for their training. The data
      on residents in training and medical school faculty provides very useful
      information for healthcare planners, state and federal government officials, and
      medical school deans and university administrators interested in addressing
      diversity issues within their respective domains.

PMID- 16296216
TI  - Factors that correlate with the U.S. Medical Licensure Examination Step-2 scores
      in a diverse medical student population.
AB  - OBJECTIVE: To assess factors that correlate with performance on U.S. Medical
      Licensure Examination (USMLE) Step-2 examination. Our hypothesis was that
      demographic factors, faculty assessments and other standardized test scores will
      correlate with students' performance on USMLE Step 2. STUDY DESIGN: A comparison
      of standardized examinations and demographic factors with USMLE Step-2 scores as
      the outcome variable was accomplished using the educational records of 171
      medical students. RESULTS: Mean USMLE Step 2, USMLE Step 1, NBME-OB/GYN and MCAT
      scores, respectively, were 190.63, 194.53, 67.47 and 24.03. Positive correlations
      of USMLE Step 2 were: USMLE Step-1 scores (r=0.681, p=0.000); MCAT scores
      (r=0.524, p=0.000); NBME-OB/GYN scores (r=0.614, p=0.000); year of OB/GYN
      rotation (r=0.432, p=0.000); faculty grades (r=0.400, p=0.000); undergraduate GPA
      (r=0.287, p=0.000); and science GPA (r=0.255, p=0.002). Negative correlations of
      USMLE Step 2 were students' increasing age (r=-0.405, p=0.000), increasing number
      of MCAT attempts (r=-0.182, p=0.000) and increasing number of NBME-OB/GYN
      attempts (r=-0.310, p=0.000). There was no correlation with gender or race.
      Logistic regression analysis showed that a failing NBME-OB/GYN score (p=0.008),
      failing USMLE Step-1 score (p=0.01), failing faculty grade (p=0.029) and multiple
      MCAT attempts (p=0.033) independently increased the risk of failing USMLE Step 2.
      CONCLUSIONS: Premedical test-taking abilities (MCAT scores), results of
      preclinical standardized tests (USMLE Step 1) and performance on clinical
      rotations (NBME-OB/GYN score and faculty grade) correlate significantly with
      USMLE scores. These findings may assist educators in selecting medical students
      at risk of performing poorly on the USMLE Step-2 examinations.

PMID- 16296217
TI  - Factors affecting medical students' selection of an internal medicine residency
      program.
AB  - OBJECTIVE: To determine factors that influence medical student selection of
      internal medicine residency programs by ethnicity and gender. DESIGN/SETTING: A
      cross-sectional mailed survey of graduating medical students applying to four
      residency programs in 1999. MEASUREMENTS: A five-point (5=most important) Likert
      scale was used to evaluate factors and included 14 items on location
      characteristics, 20 on program features, six on recruitment, three on future
      plans and three on advising. RESULTS: Of 2,820 surveys, 1,005 were completed
      (36%). The most important factors to applicants were house staff morale (mean +/-
      SD, 4.5 +/- 0.7), academic reputation (4.5 +/-0.8), and positive interview
      experience (4.1 +/- 1.0). Women rated gender diversity of faculty (3.3 vs. 2.3,
      p=0.0001) and house staff (3.3 vs. 2.5, p=0.0001), location of residency program
      near spouse (4.2 vs. 3.9, p=0.0001) or spouse's job (3.8 vs. 3.5, p=0.0002) and
      emphasis on primary care (2.9 vs. 2.4, p=0.0001) more highly than men. Minority
      applicants were more likely than whites to identify the following factors as more
      important: ethnic diversity of patients (3.8 vs. 3.4, p=0.008), house staff (3.3
      vs. 2.4, p<0.0001) and faculty (3.1 vs. 2.3, p<0.0001); service to the medically
      indigent (3.8 vs. 3.3, p=0.004); feeling of being wanted (3.8 vs. 3.4, p=0.002);
      and an academic environment supportive of ethnic minorities (3.5 vs. 2.3,
      p<0.0001). CONCLUSIONS: Location and program factors are most important in
      influencing decisions to choose a residency program. However, women and minority
      applicants also place significant importance on family and diversity factors.
      Programs need to consider differential factors in recruitment of diverse
      students.

PMID- 16296219
TI  - The missing curriculum: experience with emotional competence education and
      training for premedical and medical students.
AB  - Medical education has long overlooked teaching the normal psychodynamics of
      everyday adult life (psychonormality) in favor of training in psychopathology.
      Proficiency in psychonormality skills (i.e., emotional competence) includes
      skilled management of internal emotions, external situations and relationships,
      and promotes patient satisfaction and healthcare outcomes as well as better
      mental health for practitioners. In particular, teaching psychonormality skills
      can be helpful to underrepresented minority (URM) students whose psychonormality
      experiences may differ from the culture of mainstream medical education. This
      paper outlines a clinically derived, pragmatic, five-step course designed to
      educate and train students for emotionally competent medical practice. A real
      life example taken from an introductory workshop presentation of this course at a
      Student National Medical Association meeting is presented to illustrate the
      student-oriented application of the concepts. The enthusiastic reception accorded
      such workshops suggests an unmet need for this type of training in medical
      curricula. Benefits could include improved doctor-patient relationships and
      associated healthcare outcomes as well as higher retention of competent,
      professional, satisfied and healthier physicians, particularly URMs. Medical
      schools and residencies are encouraged to carefully evaluate the impact of
      incorporating psychonormality education and emotional competence training into
      their present curricula and faculty development.

PMID- 16296221
TI  - Xavier University premedicine program's prescription for success: an interview
      with JW Carmichael Jr., MS, PhD.
AB  - This interview of Dr. JW Carmichael was conducted for this special issue of the
      Journal of the National Medical Association, which highlights American medical
      education and the experience of African Americans. It was conducted by George
      Dawson, MD. He serves as editor of the Art in Medicine, History and Health Tidbit
      sections of the Journal of the National Medical Association. In terms of
      producing biology and chemistry majors, and, most importantly, from our
      perspective, premedicine students, the Xavier program is second to none. Under
      his leadership and with the help of his able staff, it has managed to supply more
      African-American healthcare students to professional school than any
      undergraduate programs we could find. Therefore, to us, it seemed fitting that we
      delved into his vast knowledge, in the hope that his example could be duplicated
      elsewhere and, perhaps, just maybe we can render the matter of the health
      disparaties that we speak of so often and that seemingly afflicts our community
      disproportionally.

PMID- 16296218
TI  - Knowledge of cultural competence among third-year medical students.
AB  - An increasingly diverse population and ongoing health disparities have brought
      national attention to cultural competence training in medical schools. However,
      few data exist on medical students' knowledge in cultural competence. The purpose
      of this study is to assess medical students' knowledge in cultural competence to
      identify training areas for curriculum development. All third-year medical
      students at a single institution during the period of November 2001 to February
      2004 completed a questionnaire to assess their knowledge of cultural competence
      during their medicine clerkship. The 40-item questionnaire measured several
      domains of cultural competence: health disparities, stereotyping, exploring
      culture, perceptions of health and illness, and communication/language. The mean
      knowledge score was 55%, and no student scored >80%. Race and prior cultural
      training were not predictors of overall performance.

PMID- 16296220
TI  - The cost of medical education in an ambulatory neurology clinic.
AB  - Decreased revenue from clinical services has required academic hospitals and
      physicians to improve productivity. Medical student education may be a
      significant hindrance to increased productivity and income. This study quantifies
      the amount of time spent by faculty members teaching medical students in an
      ambulatory neurology clinic as well as the amount of time students occupied rooms
      when seeing patients on their own. Over a three-week period in an ambulatory
      neurology clinic, an observer noted these quantities of time, and the opportunity
      costs of both amounts of time were determined. Attending physicians spent an
      average of 19.6 minutes per medical student per half-day teaching, which
      translates to an average cost of $20.78 per half-day clinic. Students spent an
      average of 49.9 minutes per half-day seeing patients in the absence of an
      attending physician, an opportunity cost to the clinic of $142.50 per student per
      half-day.

PMID- 16296222
TI  - Revise the premed curriculum.

PMID- 16296224
TI  - [Perioperative oxygenation and pulmonary shunt during myocardial
      revascularization in function of duration of extracorporeal circulation].
AB  - Perioperative oxygenation is of great importance for the result of operative
      treatment, especially in patients undergoing open-heart surgery. We studied
      effect of the duration of extracorporeal circulation on value of pulmonary shunt
      in 27 patients undergoing coronary artery bypass grafting surgery. The patients
      were divided into one of two groups according to the duration of extracorporeal
      circulation: A1 group--extracorporeal circulation less than 90 minutes (9), and
      A2 group extracorporeal circulation over 90 minutes (18). Measurements of
      pulmonary shunt were performed at the following times: before (I) and after
      induction of anaesthesia (II), 5 minutes (III), 2 hours (IV) and 6 hours (V)
      after extracorporeal circulation, 30 minutes after extubation (VI), 24 hours
      after extracorporeal circulation (VII), on the second (VIII), third (IX), fifth
      (X), eighth (XI) and thirteenth (XII) postoperative day. Pulmonary shunt was
      calculated according to the standard shunt equation (Berggren 1942) in control
      times I-VII, and formula of estimated shunt in control times VIII-XII. The length
      of extracorporeal circulation had influence on pulmonary shunt and oxygenation in
      patients undergoing myocardial revascularization. Extracorporeal circulation
      lasting over 90 minutes significantly increased pulmonary shunt in the first 24
      hours after extracorporeal circulation, excluding the period of artificial
      ventilation following operation. The recovery of pulmonary function occurred
      between the eighth and the thirteenth postoperative day, regardless of the
      duration of extracorporeal circulation.

PMID- 16296223
TI  - [Total intravenous anaesthesia without medical gases during economic blockade of
      the country].
AB  - In June and July 1992, when the corridor--through which we received the necessary
      medical supply--was closed, 61 patients (mostly wounded persons, 62%) underwent
      an urgent surgery. Because of the lack of oxygen and nitric oxydul, the patients
      were administered the intravenous total anaesthesia without medical gases. The
      control group was composed of 30 patients operated on in June and July 1991. The
      patients received Mydasolam (0.3 mg/kg) for general anaesthesia. Anaesthesia was
      maintained with Phentanil (15 mg/kg) and Alcurone (0.3 mg/kg). The control group
      was subjected to standard balanced anaesthesia (Thiopenton + nitric oxydul/oxygen
      + Halotin + Pancuron). The results of the two groups were compared. The observed,
      analysed and compared parameters were: the introduction period to anaesthesia,
      systolic blood pressure, diastolic blood pressure and time elapsed from the end
      of surgery to extubation. The introduction to anaesthesia was markedly
      unfavourable (p), the systolic and diastolic blood pressures, measured in five
      minute intervals during anaesthesia, were significantly lower (p). The difference
      was especially great in the period from the end of surgery to the time of
      extubation: 73 +/- 12 minutes in the studied group, and 7 +/- 5 minutes in the
      control group. The method of total intravenous anaesthesia without medical gases
      satisfied our needs and expectations during the shortage of medical supplies.
      However, the standard balanced anaesthesia is a better method because it provokes
      a faster introduction to general anaesthesia, haemodynamic effects are less
      compromized, revival from anaesthesia is faster, the use of anaesthetics and
      equipment and engagement of the personnel are not great.

PMID- 16296225
TI  - [The circadian rhythm of serum aldosterone in the diagnostics of primary
      aldosteronism].
AB  - Diagnosis of primary aldosteronism should be easy in patients with unprovoked
      hypokaliemia and hypertension. However, it is more difficult to differentiate
      patients with primary normokaliemic aldosteronism from those with essential
      hypertension with low plasma renin activity. The aim of this study was to
      evaluate the appropriate testing of diagnosis and differential diagnosis of
      primary aldosteronism. The study group consisted of 17 patients with primary
      aldosteronism (12 with aldosteronoma and 5 with bilateral hyperplasia) and 20
      patients with essential hypertension. The finding of increased serum aldosterone
      level using a single measurement, without anti-hypertensive therapy and on normal
      sodium intake is sufficient to confirm the diagnosis of primary aldosteronism
      with specificity of 95% and sensitivity of 94%. Upright posture test is shown to
      be fairly good tool in differentiation aldosteronoma and bilateral adrenal
      hyperplasia. Specificity of this test is 100% and sensitivity 88%. Although
      primary aldosteronism is not a common cause of hypertension it is reasonable to
      screen for this disorder because complete cure can be provided in a large
      percentage of patients.

PMID- 16296226
TI  - [Clinico-pathological characteristics, response to therapy and survival of
      patients with bone marrow infiltration by Hodgkin's lymphoma].
AB  - In a group of 246 patients with Hodgkin's lymphoma we found bone-marrow
      involvement in 25 patients (10.2%). Clinico-pathological characteristics,
      response to therapy and survival of those patients were compared with control
      group of 25 patients in clinical stage ill. Most of the patients with bone marrow
      involvement were older males, with "B" symptoms, bulky disease, peripheral blood
      cytopenias and elevated serum alkaline phosphatase. Bone marrow was diffusely
      infiltrated by Hodgkin's lymphoma in 17 and focally in 8 patients. Marrow
      fibrosis was noted in 19 patients. Histological type of the disease in affected
      lymph nodes was not a predictive factor for marrow involvement. Intensive
      combined chemotherapy was given to 21 patients, and 38% of them achieved
      prolonged complete remission. The four-year overall survival of 21 treated
      patients was significantly shorter than in the control group (31.3% vs. 75%,
      p=0.002). Our study showed that marrow involvement by Hodgkin's lymphoma
      indicated unfavourable prognosis, particularly in patients with marked
      splenomegaly and hepatomegaly and elevated serum alkaline phosphatase.

PMID- 16296228
TI  - [Induced abortion, epidemiological problem].
AB  - A large number of induced abortions exist in central Serbia, in spite of the fact
      that modern science made new methods and devices for the birth control available,
      which are more acceptable both from the medical and personal point of view. This
      fact shows contradictory situation and opens several questions. The crucial
      being: why do wome rely on abortion and do not use modern contraception? In
      research done in 1991--it refers to Belgrade and it includes four hundred women-
      confirmed was the accepted hypothesis that the extension of induced abortion
      developed from the discordance between comprehension of the need of birth control
      and the way it should be accomplished. The main causes of the discordance are
      insufficient knowledge about modern contraception, phychological barriers,
      insufficient cultural level (general, health, sex) of the population and lack of
      institutionalized contemporary concept fof family planning. Duration of
      prevalence of induced abortions indicates that underlying causes of frequency are
      numerous and stable over time. Considering this, and the slowness of any
      spontaneous change, it may be expected that the problem of abortions will be
      present in the years to come. However, duration of abortion prevalence will
      depend, to a large extent, on the ability and willingness of the State to cope
      with this issue.

PMID- 16296227
TI  - [Transient global amnesia--possible aetiopathogenetic mechanisms].
AB  - Transient global amnesia is a clinically well defined syndrome, characterized by
      transient isolated epizodes of confusion with inability to acquire new data,
      repetitive quieries, retrograde amnesia and absence of other neurologic symptoms
      or signs. Eighteen patients who presented at admission the clinical picture of
      transient global amnesia were, after the examination, classified in three groups:
      patients with symptoms or signs of transitory focal ischemia, migraine group, and
      miscellaneous group. The transitory global amnesia in patients suffering from
      atherosclerotic changes of the vascular system is usually the first manifestation
      of transitory ischaemic attack pointing to the vascular insufficiency of the
      posterior cerebral regions as the cause of attack. The typical transient global
      amnesia is not a rare phenomenon, but it supposes the existence of the
      precipitating factors. Although its "pure" form is usually benign, the appearance
      of other factors such as cerebral neoplasms, involved in the aetiology of
      transient global amnesia, requires the complete clinical examination of each
      individual with these symptoms.

PMID- 16296229
TI  - [In vitro reactivity of lymphocytes after the addition of immunostimulatory
      drugs].
AB  - The in vitro immunomodulating, effects of two thymic extracts--Thymex L and
      Thymomodulin--on lymphocytes of lung cancer patients, were studied. The number of
      total and active T cell and PHA-induced lymphoproliferative response were
      evaluated before and after the addition of two different concentrations (5 mg/ml
      and 0.5 mg/ml) of these agents. The in vitro incubation with Thymex L and
      Thymomodulin had no effect on the number of total T lymphocytes, but the active T
      cells and proliferative responses were significantly higher. This increases was
      observed in the majority of patients with diminished baseline values. These
      results indicated that several immunological parameters should be used in vitro
      testing of an immunomodulatory drug. They also indicated the need for in vitro
      testing selection of candidates for immunotherapy among immunodepressed cancer
      patients.

PMID- 16296230
TI  - [Effect of heavy metals on symptoms of high-risk pregnancy].
AB  - The authors studied the effect of working conditions and harmful organic solvents
      on the frequency of gynaecological diseases and menstrual disorders in 138 women.
      The experimental group consisted of 88 women exposed to evaporation and increased
      concentrations of organic solvents, and the control group was composed of 50
      employees without any harmful effect of these noxa. It was found that adnexitis
      and dysmenorrhea were more frequent in the experimental group than in the control
      group, and that the statistical difference was significant (p<0.05). However, the
      frequency of gynaecological diseases, such as haemorrhages and menstrual
      disorders, were almost the same in both groups, without a statistically
      significant difference (p>0.05).

PMID- 16296231
TI  - [Current concepts on the treatment of glioma of optic nerve and chiasm].
AB  - Based on the data from literature, the authors present current concepts on the
      treatment of glioma of the optic nerve and chiasm. The influence of location and
      biological behaviour of these tumours on making decision about the most
      appropriate treatment regarding the results and minimum of side-effects, is
      emphasized.

PMID- 16296232
TI  - [Quantitative approach to dialysis adequacy (part two)].
AB  - A quantitative assessment of dialysis and prescription of dialysis as therapy in
      every single patient have always been a continuous problem. Numerous efforts have
      been made to date to determine the kind of therapy for patients on hemodialysis
      on the basis of simple objective indices instead of clinical and laboratory
      parameters. Some of these indices have been widely accepted nowadays. Although
      the main clinical and laboratory parameters have still been currently applied in
      the assessment of peritoneal dialysis adequacy, serious quantitative approaches
      are made even in these cases regarding the more accurate therapy. The first part
      of the article deals with the development of quantitative approach to dialysis
      adequacy in certain models; the second part concerns dialysis prescription based
      on Gotch's and Sargent's modification of the American National Cooperative
      Dialysis Study (NCDS) as well as on Direct dialysis quantification (DDQ) and
      peritoneal dialysis adequacy.

PMID- 16296233
TI  - [Effects of urban noise on mental health].
AB  - The results of the latest studies on the effects of urban noise on mental health
      are presented in this paper. Numerous psychiatric symptoms have been frequently
      noticed in the population of the settlements with a high level of urban noise:
      fatigue, headaches, tension, anxiety, irritability, bad concentration, insomnia,
      whith a consequently high consumption of psychotropic medicines. Higher admission
      rates in psychiatric hospitals have been noticed from noisy areas in comparison
      with low noise regions. By use of diagnostic psychiatric interviews it has been
      shown as well, that in sensitive categories of population positive correlation
      can be expected between the number of persons with mental disorder and the level
      of environmental noise. Noise annoyance and sleep disturbance, namely shortening
      or absence of the sleep phase 4 and REM, are the basic negative psychological
      effects of noise, with an adverse effect on mental health in general.

PMID- 16296234
TI  - [Acute myeloblastic leukemia during pregnancy].
AB  - We present a pregnant woman, with diagnosis of acute myeloblastic leukemia (AML)
      established in the third trimester of pregnancy. She was delivered by Caesarean
      section at the end of 36th gestational week, and a healthy, mature-for-date, male
      infant was born. Combined chemotherapy (YU-AML protocol) was administered a week
      after the delivery, but the patient died after 7 months, due to resistant
      disease. We discuss actual problems that make an approach to pregnant patient
      with AML specific and individual.

PMID- 16296235
TI  - [Ishiadic hernia (sciatic hernia)].
AB  - The sciatic hernia is a protrusion of the peritoneal sac and its contents through
      the great or small sciatic foramen. This kind of hernia is an extremely rare. The
      authors present patient with ischiadic hernia and its operative repair. The
      preoperative diagnosis was a tumour (cyst) localized intraglutealy, but during
      operation sciatic hernia was found. Hernia was operatively removed making an
      oblique incision over the palpable mass, splitting the gluteous maximus, and
      exposing and opening the hernial sac, avoiding nerve and vascular injury by
      careful dissection of the sac. Then the sac was ligated and excised. Closing of
      the musculature defect was made with interrupted sutures of 000-Dexon,
      aproximating the gluteus maximus and medius muscles to the musculus piriformis.
      The authors consider that transgluteal approach has priority to transabdominal
      approach.

PMID- 16296236
TI  - [Sezary's syndrome (case report)].
AB  - The Sezary's syndrome is a lymphoproliferative disorder from the group of
      chronical lymphocytic leukaemia originated from the T-cell lineage. Authors are
      presenting the patient with Sezary's syndrome for the first time ever diagnosed
      in the Institute of Haematology. The patient, 58 years old got ill in summer
      1989. with the symptoms of strong itch and erythematous papullas over the sin. In
      April 1990. he came to the Institute of Hematology where he was diagnosed as a
      Sezary's syndrome case on the evidence of generalized erythrodermia,
      identification of lymphocytes with cerebriform nucleus in peripheral blood and
      membrane-marker analysis that showed aberant post-thymic proliferation of T
      lymphocytes in bone marrow. The patient wastreated with a polychemiotherapy and
      with "electron beam" therapy with temporary improvement, but died in January 1991
      with sepsis and a hepathorenal syndrome.

PMID- 16296237
TI  - [Patulous eustachian tube].
AB  - Patulous eustachian tube is a pathological condition which exists more often than
      we make a diagnosis, and a patient is not often aware of his disease. This
      disease can be manifested with various symptoms: respiratory synchrony noises in
      the ear, because of the penetration of the air current through the eustachian
      tube and with the movement of the eardrum outwards and inside, with autophony,
      reduction of the hearing, the buzzing, dizziness and disturbance of the balance.
      Two patients are presented. The first one was sick for many years from various
      chronics exhausted diseases: Jackson's epilepsy, temporary vascular brain
      disturbances, tuberculosis of lung, stomach ulcer, heart diseases, the patient is
      from low class, on one side, and also suffers from some local diseases: a
      paralysis of soft palate and palatal arcs, a chronic catarrhal rhinitis and
      sinusitis, a deviation of nasal dividing wall and hindered breathing through the
      nose, on the other side. Many years the patient didn't know for patological
      condition in the ears and in the eustachian tubes. After improving the hygienic
      conditions, the physical condition and local therapy, the patient felt much
      better. The second patient, with considerable shorter evolution of the disease
      and mild symptomatology, showed the amplified symptoms of the disease of the
      Eustachian tube in the course of the acute otitis. It is attained a satisfying
      calming of the manifestative symptoms by remedy therapie. Man must thing about
      possibility of the appearance of this pathology condition in various disease or
      conditions, which can take to the fast lost of the weight and physical and moral
      exhaustion of the patient, i.e. an adult, first as the protection of the
      appearance of the disease (condition) and afterwards, eventually early and
      regulary treatment in order to prevent various possible, above mentioned
      complications.

PMID- 16296238
TI  - [Multidisciplinary investigations in dead persons suspicious of AIDS].
AB  - The background of AIDS is the deregulation of the cellular immune system caused
      by HIV infection. AIDS has proved to be entirely different from any previous
      known diseases. It affects practically all the tissues and organs of the human
      body. Clinical and autopsy diagnoses are confronted with an incomparable
      diversity of inflammatory, vascular, degenerative and neoplastic changes. Thanks
      to clinical and pathological researshes, the medical knowledge of AIDS has
      rapidly progressed. The Institute of Forensic Medicine is, for now, the unique
      medical institution organized to perform obligatory autopsies of drug-addicts, to
      detect the other cases suspect of HIV infection or some AIDS indicative diseases.
      The aim of this study is to establish the basis for multidisciplinary
      investigations of AIDS and to solve very important problems such as: a) to accept
      the diagnostic criteria for correct diagnosis of AIDS, with or without laboratory
      evidence of HIV infection; b) to recognize the early stadium of clinico
      pathological entities associated with HIV infection; c) to improve the
      "indicator" of AIDS disease for daily medical practice.

PMID- 16296239
TI  - [Effect of all-trans retinoic acid on the newly diagnosed acute promyelocytic
      leukaemia: our experience].
AB  - Acute promyelocytic leukaemia (APL) is characterised by the morphology of bias
      cells (M3), t(15;17) translocation, and coagulopathy combining disseminated
      intravascular coagulation (DIC) and fibrinolysis. Anthracy cline-cytosine
      arabinoside (Ara C) intensive chemotherapy yields a complete remission in 50
      percent (%) to 80% of newly diagnosed APL patients. Failure to achieve complete
      remission results in fatal bleeding due to coagulopathy or fatal sepsis during
      the phase of aplasia. It has been recently shown that all trans retinoic acid
      (ATRA) selectively differentiates abnormal promyelocytes into mature granulocytes
      in APL, both in vitro and in vivo, and induced complete remission in 80% to 90%
      of the newly diagnosed patients. It has also been observed that therapy with ATRA
      rapidly improved coagulopathy, and induced no aplasia. However, in 30% of
      patients the treatment with ATRA as a single drug was associated with rapid
      increase in leukocytes and signs of "ATRA syndrome", which could have fatal
      outcome. Therefore the European study group initiated in 1991 a multicentre
      randomised trial comparing chemotherapy with daunorubicin Ara C (chemotherapy
      group) and ATRA combined to the same chemotherapy (ATRA group) in newly diagnosed
      APL patients, aged 65 years or less. Results of this study strongly suggest that
      ATRA should be incorporated in the front line therapy of newly diagnosed APL. The
      aim of our study was to confirm their results in our newly diagnosed patients.
      PATIENTS AND METHODS: In our study we had 15 subsequently hospitalised patients
      with APL in whom diagnosis was made according to MIC classification, and who were
      treated with ATRA (Vesanoid-Hoffman La Roche) combined with chemotherapy
      according to the recommendation of the European study groups. The comparison of
      the effect of ATRA we has evaluated by the outcome of APL in 12 patients who
      received only combined chemotherapy in induction phase according to the Yu-AML-89
      protocol 12 or 01-AM-86 protocol. Both protocols include daunorubicin and Ara C.
      In all patients MIC classification was performed. Characteristics of the patients
      included in the study with special emphasis to symptoms at presentation, are
      given in Table 1. TREATMENT: Patients treated with ATRA plus chemotherapy
      received daily oral dose of ATRA 45 mg/m2 until the complete remission, or for a
      maximum of 90 days. After complete remission they received three courses of
      daunorubicin 60 mg/m2 for 3 days, and Ara C 200 mg/m2 for 7 days. However, course
      one was added to ATRA on day one of treatment of initial leukocyte counts were
      greater than 5 x 10(9)/L or rapidly started to increase to above 6 x 10(9)/L or
      more. Patients treated with chemotherapy received only in induction phase
      daunorubicin 45 mg/m2 for 4 days and Ara C 200 mg/m for 7 days as well as the
      intensive platelet support, heparin, fresh frozen plasma in those with bleeding.
      During the study haemostasis monitoring was performed in all patients. Complete
      remission was defined according to the criteria of the European study group.
      Early death was defined as a death during the therapy with ATRA or chemotherapy
      due to "ATRA syndrome", bleeding, aplasia, or resistant leukaemia. Statistical
      analysis was performed according to the Kruskal-Wallis test. RESULTS: Relevant
      haematological and pathobiological characteristics at presentation are shown in
      Table 2. It can be seen that there were no significant characteristic differences
      at presentation between ATRA group and chemotherapy group. The effects of the
      treatment are shown in Table 3. It can be seen that complete remission was
      achieved in 87% of patients receiving ATRA combined with chemotherapy and only in
      42% of patients who received combined chemotherapy. This difference is
      significant (p < 0.01). Duration of complete remission lasted for 14 months
      (median) in the patients receiving ATRA while only 5 months (median) in the
      patients who received combined chemotherapy. Fatal outcome in ATRA group occurred
      in 13% due to the "ATRA syndrome" and in 58% of the patients treated with
      combined chemotherapy due to bleeding. Table 4 shows four selected patients from
      ATRA group in whom complete remission was followed with disappearance of t
      (15;17), thus providint the evidence of the eradication of clonal abnormalities.
      It should be emphasised that 2 of 15 patients developed ATRA syndrome during the
      early phases of the treatment with a feature of cardiorespiratory distress. The
      therapy with steroid was unsuccessful. Nine of 13 patients in ATRA group had
      moderate side effects with no necessity to discontinue the therapy. DISCUSSION:
      Our clinical trial shows for the first time in our county a beneficial effect of
      ATRA in addition to chemotherapy compared with chemotherapy alone in newly
      diagnosed APL, thus comfirming the results of the European study group. The only
      flaw of in our study may come from the fact that the patients included in the
      study were not randomised and that for the comparison of the ATRA group were used
      previously treated patients with chemotherapy alone. However, we believe that
      this flaw has been overcome since uniform diagnostic procedure and particularly
      MIC classification were performed in all patients. In addition to that, all
      patients included in the trial were subjected to the analysis of haemostatic
      status as well as to precise biochemical studies, ECG and abdominal echography.
      It is interesting to note that in our study, similarity to the European study
      group, 13% of patients developed "ATRA syndrome". Therefore, it is recommended
      that further effort should be made in order to prevent this fatal and not yet
      resolved syndrome.

PMID- 16296240
TI  - [The role of endothelin in acute renal failure].
AB  - During the study of the pathological significance of circulating endothelin (ET)
      in acute renal failure (ARF) we measured ET in 7 children (mean age 8.8+4.4
      years) with ARF in the most severe phase, and 3.7+3.5 months later in the
      recovery period. Twenty-seven healthy children (mean age 11.1+/- 6.3 years) were
      included in the study as controls. Plasma ET level was measured by highly
      sensitive and specific radioimmunoassay for ET-1 and ET-2 (ET 1/2, Biomedica,
      Vienna). Plasma ET was significantly higher in the most severe phase of ARF than
      in the recovery period, but comparing to plasma ET in the healthy children, the
      difference was only on borderline statistical significance. Since plasma
      concentrations of creatinine did not correlate with plasma ET in patients, either
      in acute or in the recovery phase of disease, we concluded that decreased
      glomerular filtration (GFR) was not the main factor determining the increased ET
      in ARF. We suggest that elevated plasma ET in ARF may be secondary to vascular
      endothelial dysfunction and speculate that engancement synthesis of endothelial
      relaxing factor (EDRF) inhibits ET synthesis during the recovery period. The
      pathogenetic role of circulating ET in ARF cannot be determined from the present
      study.

PMID- 16296241
TI  - [Atrial natriuretic peptide in children with nephrotic syndrome].
AB  - The mechanism causing sodium retention in nephrotic syndrome remains
      controversial. There is an increasing evidence that sodium retention is directly
      due to an intrarenal mechanism. Atrial natriuretic peptide (ANP), realized from
      the heart during hypervolaemia, increases glomerular filtration rate, renal
      sodium and water elimination in both experimental animals and healthy men. In
      attempt to clarify the possible role of ANP in the mechanism of sodium retention
      in nephrotic syndrome we carried out this study. The purpose was: a) to determine
      plasma concentrations of ANP and values of creatinine clearance (CCr),
      natriuresis and diuresis both in basal conditions and after remission of the
      ilness, and b) to analyze the influence of acute hypervolaemia on ANP, Ccr,
      diuresis and natriuresis. A group of 12 children (aged 2-13 years) was studied
      during relapse and remission of nephrotic syndrome. In addition, 8 patients were
      studied during acute hypervolaemia due to intravenous infusion of 12% albumine.
      Twelve healthy children served as control group. Our results showed that in
      nephrotic syndrome group ANP was higher than in control group. Creatinine
      clearance, diuresis and natriuresis were significantly lower during relapse than
      in remission. The increase in Ccr, diuresis and natriuresis were observed during
      infusion of albumine, but no correlation was found between increased ANP and
      other parameters. This study showed that during relapse of nephrotic syndrome
      plasma concentrations of ANP are moderately elevated, but Ccr, diuresis nad
      natriuresis are blunted. We speculate that natriuretic and diuretic effects of
      ANP are impaired in children with nephrotic syndrome.

PMID- 16296242
TI  - [Thyroid gland disease mortality in Yugoslavia from 1987 to 1992].
AB  - The aim of this paper was to obtain the data on mortality rate due to thyroid
      glang diseases in FR Yugoslavia from Mortality Banc Data, and to compare them
      with data about the total mortality in Yugoslavia, and to mortality rate due to
      other endocrine gland diseases over the period from 1987 to 1992. The obtained
      data indicate that the average mortality rate (number of cases per 100,000
      inhabitants) due to thyroid gland diseases was 0.72 and 2.45% of deaths related
      to other endocrine glands. The main causes of death were adenocarcinoma
      thyreoideae (72.3%) and hyperthyreosis (19.0%). In total number of deaths due to
      adenocarcinoma 65.75% were women and 34.25% men; and in total number of deaths
      related to hyperthyreosis 88.24% were women and 11.76% men.

PMID- 16296244
TI  - [Otogenic brain abscess].
AB  - The authors report the 20-year experience in the diagnosis and treatment of
      patients with otogenic brain abscess. In the studies were included 36 patients of
      whom 24 had a cerebral abscess and 12 a cerebell abscess. The otogenic brain
      abscess was usually associated with meningitis (45%). Headache and temperature
      were common with otogenic intracranial complications. The active chronic otitis
      with cholesteatoma was usually found in the middle ear. The inflammatory process
      was usually spread in the endocranial space through destroyed walls of the midle
      ear. Computerized tomography (CT) is the most safe method in the diagnosis of
      brain abscess, by which it is possible to localyze the abscess, to plan the
      operation and follow-up the success of treatment. Neurological and
      ophthalmological examinations cannot always detect brain abscess. The authors
      suggest that in cases of brain abscess, it is important to neurosurgically remove
      the abscess. After improvement of the general condition of the patient,
      otosurgical procedure must be done. In this group of patients mortality is
      relatively high, both in abscessus cerebri (20%) and abscessus cerebelli (25%).

PMID- 16296243
TI  - Spectroscopic and electrochemical investigations of some calcification phenomena
      in ophthalmology and pulmology.
AB  - The application of the cyclic voltammetry and UV-VIS as well as IR spectroscopy
      in the analysis of some calcification phenomena which occurred in human body have
      shown useful and interesting results. Sometimes the defense process of the human
      organism in the presence of foreign particles in the injured part of the body is
      the isolation of these particles with the calcification processes. The calcified
      worm surgically extracted from the human eye fifty years after its penetration
      has been analyzed, and the history of its penetration and behavior in the human
      eye is better understood with cyclic voltammetry and IR spectroscopy. The similar
      effects were observed in the analysis of calcified foreign body which was found
      in the human bronchus. The results of the analysis contributed to the little
      believed possibility that complete biological death of all cells could not occur
      inside the calcification even after many years of their presence in the human
      body. Further work is needed for the complete understanding of the observed
      phenomena. The UV-VIS, IR spectroscopic and cyclic voltammetry investigations are
      another contribution to the application of chemistry in medicine to mutual
      benefit.

PMID- 16296245
TI  - [Thyroid carcinoma in childhood].
AB  - A retrospective analysis of the thyroid gland carcinoma in children, cured at the
      Institute of Oncology, was more frequent in girls (76%) than in boys. The changes
      were analysed according to TNM classification using the protocol for diagnostic
      and treatment procedures. The approach of the protocol was the same for children
      and adult population. In children the primary process ecpanded very fast in
      regional lymph nodes. Surgery of different size with or without the functionally
      neck dissection, proved the pathohistological verification. After the surgery, in
      10 of 29 children, 131-I was applied. Spreading of the disease in lungs was
      observed in four of 29 children. The parameters of the successful therapy of the
      thyroid gland carcinoma in childhood were the general status, local status, the
      concentration of thyroglobulin value (Tg), and the serum titres of
      antithyroglobulin antibodies.

PMID- 16296246
TI  - [Niemann-Pick disease (type C)].
AB  - A 15-year old girl with slowly progressive gait and speech disorders, and with
      impairment of mental ability, is decsribed. The disease appeared 18 months before
      the first hospitalization at the Department of Neurology and Physchiatry for
      Children and Young People. Neurological and other examinations confirmed
      extrapyramidal and cerebellar signs, conspisuous knee and ankle reflexes, marked
      splenomegaly, slightly enlarged liver, sometimes emotional incontinence and
      global physic deterioration. The clinical picture was similar to Wilson's
      disease. However, in liver and bone marrow, as well as during sternal pincture
      macrophages (foam cells) were detected as characteristic elements of Niemann-Pick
      disease. The authors conclude that the patient belongs to type C of Niemann-Pick
      disease with a relatively benign course.

PMID- 16296247
TI  - [Malignant otitis externa with diabetes mellitus insulin-dependent patients].
AB  - Malignant otitis externa is non-taming skin and soft tissues of the outer hearing
      canal infection tending to expand towards temporal bone and the base of the
      skull. The infection is usually caused by Pseudomonas aeuroginosa, sometimes by
      Staphilococcus aureus or Klebsiela. In 90% cases the patients are diabetics,
      mainly in older age. A nineteen years old girl with insulindependent diabetes
      mellitus and having malignant externa is shown.

PMID- 16296248
TI  - [Chronic immune thrombocytopenic purpura in pregnancy--a case report].
AB  - The authors present a young woman with chronic immune thrombocytopenic purpura
      during pregnancy. This association is the commonest cause of thrombycitopenia in
      the first three months of pregnancy. There is a bigger number of spontaneous
      abortions and more frequent bleeding in such patients, during delivery, in
      mothers and babies too. The number of mothers platelets and the level of
      circulating IgG antibodies associated to the mothers platelets are not reliable
      indicators of the fetus platelets number. Only reliable way for determination of
      the fetus platelets number is percutaneous umbilical cord blood sampling. Five
      days before delivery the fetus platelets number have been determinated by this
      method, and it was 260 x 10(9)/l. Mother was prepared for delivery with high
      doses of prednisone of 1 mg/kg body weight. Her platelets number was 128 x
      10(9)/l on the day of delivery. Delivery has been performed by vaginaly route
      without complications. Healthy female baby was born.

PMID- 16296249
TI  - [Stroke as a probable cause of death in some Serbian medieval rulers].
AB  - The medical analysis of illnesses and causes of death of Serbian rulers in the
      Middle-Ages, is difficult. Only a tentative diagnosis can be made. In addition to
      their religious character old Serbian biographies offer many information; they
      are, however, often insufficient and fragmentary. While the true state of health
      of Serbian rulers cannot be known, there are some descriptions and documents
      useful for such attempts. Stroke was presumed to be the cause of death of some
      Serbian medieval rulers. According to his biographers, Teodosije and Domentian,
      King Stefan Prvovenchani (First-Crowned) (1217-1228) had two apoplectic
      accidents. When the first stroke occurred, he was paralytic, bedridden and
      loozing his general strenght. According to St. Sava he very well recovered after
      the first stroke. The second stroke, in the near future, was fatal. Some authors
      supposed the abuse as ethyl that impaired his health. King Stefan Urosh II
      Milutin (1282-1321) died as a seventy years old man. His biographer, Archbishop
      of Petsh, Danilo II wrote about a sudden onset of the disease. King Milutin was
      paralyzed and aphasic. In the terminal stage, he was unconscious and insensible.
      Preceding stresses may be an aetiological factor. According to Constantine the
      Philosopher, biographer of despot Stefan Lazarevitsh (1402-1427), this ruler died
      when he was 53 years old. The onset of the disease was sudden. Despot showed
      motor weakness, dyscoordinated movements, disordered balance and sensorium,
      speaking disturbances, and paralysis. He died in coma next morning, on July 18,
      1427. This clinical feature suggests possible cerebro-vascular insult. It is not
      clear whether the existing rheumatic disease played a certain role in the
      aetiolotgy of stroke in this case. Some data suggested the emotional lability and
      incontinence as warning symptoms.

PMID- 16296250
TI  - [How the epidemics of typhus and relapsing fever were stopped in Serbia in 1915
      year].
AB  - Eighty years are passed after the catastrophic epidemics of Typhus and Relapsing
      Fever in 1915 in Serbia was stopped and put under control. This remarkable
      achievment was realized in cooperation of the British Military Mission and
      Serbian health services, one month before the usual seasonal maximum of epidemic
      wave. The cutting of epidemics was made possible by introducing famous "Serbian
      barrel" (constructed by Dr Stammers). However, the epidemics of Typhus fever
      present in the same time in several european countries lasted throughout the
      whole First World War.

PMID- 16296251
TI  - A comprehensive system for washing, pre-disinfecting and sterilizing of dental
      and surgical instruments.
AB  - PURPOSE: The purpose of this study was to test and describe in detail a newly
      developed comprehensive system for washing, pre-disinfecting and sterilizing of
      dental and surgical instruments. MATERIALS AND METHODS: The system consists of a
      combined washing and steam-operated pre-disinfection apparatus and newly
      developed trays, in which assorted instruments can be washed and disinfected
      without handling individual instruments. The system was subjected to a large
      number of tests. RESULTS: The cleaning efficiency of blood-soiled instruments was
      found to be excellent. The disinfection of dental instruments contaminated with
      bacteria, yeast and non-enveloped virus showed decimal reduction factors that
      were equivalent to sterilization. The trays had optimal sealing qualities. Their
      steam permeability was perfect even after prolonged use in N-, S- and B-type
      autoclaves. However, long-term tests in a clinic revealed shortcomings with
      regard to insufficient drying of instruments in the wash/disinfection apparatus.
      Furthermore, the mechanical stability of the polysulfonate tray covers needs to
      be improved. Occasionally, after extended use, the fit of the filters in metal
      trays became inadequate, in particular when trays were sterilized for 18 min at
      134 degrees C for a prolonged period of time. CONCLUSION: In spite of the above
      mentioned shortcomings, the system shows great labor and cost-saving potential,
      allowing a new approach to instrument recirculation and workflow in the dental
      office.

PMID- 16296252
TI  - Poor overall diet quality as a possible contributor to calculus formation.
AB  - PURPOSE: An association between diet and calculus deposits was suggested by
      animal studies. The objective of the present analysis was to examine whether or
      not there is an association between overall diet quality, as measured by the
      healthy eating index, and extent of dental calculus deposits using a subset of
      the third National Health and Nutrition Examination Survey (NHANES III) data.
      MATERIALS AND METHODS: NHANES III participants 18-years of age or older who had
      data on dental calculus and diet quality were selected (n = 12405). The healthy
      eating index (HEI), used as an indicator of overall diet quality, has a minimum
      score of zero (poorest) and a maximum score of 100 (best) and was divided into
      three categories, poor (HEI < 51), fair (HEI, between 51 - 80) and good (HEI >
      80). Ordinal logistic regression models were used to examine the association
      between the HEI and the percentage of sites with calculus deposits. RESULTS:
      Overall diet quality was found to be significantly associated with calculus
      deposits controlling for: age, gender, race, education, poverty income ratio,
      smoking, diabetes, history of vitamin and mineral use, body mass index, time
      elapsed since last dental visit and gingival bleeding. The adjusted odds ratios
      for having a greater percentage of sites with calculus were 1.54 (1.19 - 1.98),
      1.30 (1.02 - 1.60) and 1.00 (reference) for subjects with poor, fair, and good
      diet quality respectively. CONCLUSION: Poor diet quality is significantly
      associated with more calculus deposits. Further studies are needed to examine if
      poor diet quality is a predisposing factor for calculus formation and/or a risk
      factor for periodontal diseases.

PMID- 16296253
TI  - Tobacco smoking and gingival health in a Saudi Arabian population.
AB  - PURPOSE: While cigarette smoking is recognized as being detrimental to
      periodontal health, the effect of water pipe smoking on gingival health is not
      known. The present study was conducted to determine whether water pipe smoking
      has an influence on gingival health. MATERIAL AND METHODS: A cross-sectional
      study was carried out in 244 individuals aged 25-70 years. The levels of plaque
      and gingivitis were recorded on four sites of all present teeth, using the plaque
      index (PI) and gingival index (GI). Information about oral hygiene practices,
      dental care and smoking habits was obtained at the time of the clinical
      examination in accordance with a predetermined questionnaire. RESULTS: The means
      of plaque index and gingival index values were 1.2 and 0.9, respectively.
      Similarly, the mean percentages of surfaces with plaque and gingival bleeding
      sites were 66.7% and 30.4%, respectively. There was an overall significant
      association between smoking and plaque index and gingival index (F = 22.9 and F =
      10.8, respectively, p < 0.001). Oral hygiene was inferior in water pipe smokers,
      cigarette smokers, and mixed smokers when compared to non-smokers. The
      correlation between plaque % and gingival bleeding % in cigarette smokers was
      significantly weaker than in non-smokers. It was also weaker in water pipe
      smokers, but the difference was not statistically significant. CONCLUSION: The
      gingival bleeding response to plaque was significantly suppressed in cigarette
      smokers. There was a tendency towards suppression also in water pipe smokers.

PMID- 16296254
TI  - Periodontal conditions in Switzerland at the end of the 20th century.
AB  - AIM: To epidemiologically assess the periodontal conditions of the adult
      population in Switzerland. MATERIAL AND METHODS: During a ten-year period, a
      total of 1318 subjects were randomly selected on the basis of a process involving
      the community rosters in seven regions (Cantons) of Switzerland: (Canton of
      Berne; Canton of Zurich; Western cantons (GE,VD,NE); Eastern cantons
      (SG,AI,AR,TG,SH); Southern cantons (VS,GR,TI); Central cantons
      (LU,GL,ZG,UR,SZ,OW,NW) and Northern cantons (JU,FR,SO,AG,BL)) and encompassing
      all adult age groups (20-89 years). The subjects were examined in dental offices
      randomly distributed throughout the country. The number of teeth present, the
      mean Plaque and Gingival as well as Retention Indices were assessed. Furthermore,
      pocket probing depths and loss of periodontal attachment were determined on all
      teeth. RESULTS: Ninety-four (7.1%) of the subjects were completely edentulous
      leaving 1224 dentate individuals with an average of 21.65 teeth for analysis. In
      the youngest cohort (20-29 years) 27.03 teeth were present. During the fourth to
      the seventh decade of life, tooth loss appeared to follow a linear pattern
      leaving 17.63 teeth in the age group of 60-69 years. The oldest age group of the
      80-89 years old yielded 11.08 teeth. The mean scores of all clinical parameters
      increased significantly with increasing age. Mean PII in the youngest age group
      was PII: 0.72 (SD: 0.38) and reached PII: 1.55 (SD: 0.68) in the oldest. The
      corresponding mean GI were 1.17 (SD: 0.31) and GI: 1.64 (SD: 0.50), respectively.
      The mean RI increased from 0.24 (SD: 0.29) to RI: 1.34 (SD: 0.70) in the oldest.
      Mean probing depth increased slightly from 20 to approximately 49 years.
      Thereafter, mean PPD remained around 3.0 mm. The loss of periodontal attachment
      increased dramatically after the age of 50. CONCLUSIONS: Periodontitis manifests
      itself after the age of 50. The pronounced progressive attachment loss in the age
      cohorts over fifty years explained the marked loss of teeth in some individuals.
      From a public health point of view, it is indicated to make a major effort for
      periodontal prevention in the population approaching the second third of life.

PMID- 16296255
TI  - An experimental gingivitis study to evaluate the clinical effects of a stannous
      fluoride dentifrice.
AB  - PURPOSE: A double blind, controlled, parallel group trial utilizing the
      experimental gingivitis model was performed on thirty young adults to evaluate
      the clinical effects of a 0.45% stannous fluoride dentifrice used as a slurry on
      dental biofilm formation and the development of gingivitis. MATERIAL AND METHODS:
      Following a thorough examination and oral prophylaxis procedures, subjects were
      randomly assigned to apply one of the following dentifrices twice daily over a
      three-week period: A) dentifrice slurry without active ingredients; B) 0.45%
      stannous fluoride gel; and C) Colgate Total dentifrice slurry (0.30% triclosan,
      0.24% sodium fluoride, 2% copolymer). RESULTS: After three weeks, the stannous
      fluoride dentifrice significantly (p < 0.05) reduced gingivitis compared with the
      Colgate Total group by 39.7%. Gingival bleeding was also reduced relative to the
      Colgate Total group. This difference was statistically significant (P < 0.05).
      During the experimental period, the mean PII scores increased almost linearly in
      all three groups without yielding any statistically significant differences.
      CONCLUSIONS: The results of this clinical trial demonstrated that, over a three
      week period, the application of a 0.45% SnF2 gel significantly inhibited the
      onset of gingivitis compared to Triclosan/sodium fluoride/copolymer (Colgate
      Total). However, neither stannous fluoride nor Triclosan/sodium fluoride/
      copolymer (Colgate Total) possessed sufficient antimicrobial activity to suppress
      biofilm formation in the absence of regular oral hygiene practices.

PMID- 16296256
TI  - Quantification of root caries using optical coherence tomography and
      microradiography: a correlational study.
AB  - PURPOSE: The use of transverse microradiography (TMR) to quantify the amount of
      mineral lost during demineralization of tooth tissue has long been established.
      In the present study, the use of an en-face Optical Coherence Tomography (OCT)
      technology to detect and quantitatively monitor the mineral changes in root
      caries was investigated and correlated with TMR. MATERIALS AND METHODS: We used
      an OCT system, developed initially for retina imaging, and which can collect A
      scans, B-scans (longitudinal images) and C-scans (en-face images) to
      quantitatively assess the development of root caries. The power to the sample was
      250 microW, wavelength lambda = 850 nm and the optical source linewidth was 16
      microm. RESULTS: Both the transversal and longitudinal images showed the caries
      lesion as volumes of reduced reflectivity. Quantitative analysis using the A-scan
      (reflectivity versus depth curve) showed that the tissue reflectivity decreased
      with increasing demineralization time. A linear correlation (r = 0.957) was
      observed between the mineral loss measured by TMR and the percentage reflectivity
      loss in demineralized tissue measured by OCT. CONCLUSION: We concluded that OCT
      could be used to detect incipient root caries, and that the reflectivity loss in
      root tissue during demineralization, measured by OCT, could be related to the
      amount of mineral lost during the demineralization.

PMID- 16296258
TI  - Oral hygiene habits and oral health awareness among urban Saudi Arabians.
AB  - PURPOSE: To analyze prevailing oral hygiene practices and oral health awareness
      among urban Saudi Arabians in relation to age, gender and educational level.
      MATERIALS AND METHODS: Structured interviews with 1155 regular patients at two
      centers providing dental care for university and military staff and their
      families, respectively, in the city of Makkah. Consecutive patients were
      stratified by gender and age, into 6 categories from 10 to 60 years, with 50 male
      or female subjects in each group at each center. Oral hygiene habits and
      attitudes to oral health were correlated with age, gender and educational levels,
      using ANOVA. RESULTS: For the majority (> 88%) oral hygiene routines were
      introduced very late, after the age of 7 yr. Habits were strongly correlated to
      the level of education (p < 0.001); subjects with less education favored the
      miswak. Among the better educated, toothbrushing started earlier (p < 0.001).
      Regular miswak use was more frequent in older age groups (p < 0.001). Females
      used a toothbrush more often than males (p < 0.001), and miswak use by women was
      less frequent than by men (p < 0.001). Despite the availability of free dental
      care at the public health centers, 89% of the participants at the military center
      sought only emergency care, in contrast to 54% at the university center.
      CONCLUSIONS: Among urban Saudi Arabians, oral hygiene routines are introduced
      relatively late in life and knowledge and awareness of oral health is very low.
      There are pronounced variations in oral hygiene habits, related mainly to age and
      educational levels. Such factors should be taken into account when planning oral
      health strategies.

PMID- 16296257
TI  - The measurement of enamel wear of two toothpastes.
AB  - PURPOSE: The aim of this study was to compare the enamel abrasivity of a
      whitening toothpaste with a standard silica toothpaste. MATERIALS AND METHODS:
      Polished human enamel blocks (4 x 4 mm) were indented with a Knoop diamond. The
      enamel blocks were attached to the posterior buccal surfaces of full dentures and
      worn by adult volunteers for 24 hours per day. The blocks were brushed ex vivo
      for 30 seconds, twice per day with the randomly assigned toothpaste (n = 10 per
      treatment). The products used were either a whitening toothpaste containing
      Perlite or a standard silica toothpaste. After four, eight and twelve weeks, one
      block per subject was removed and the geometry of each Knoop indent was re
      measured. From the baseline and post-treatment values of indent length, the
      amount of enamel wear was calculated from the change in the indent depth.
      RESULTS: The mean enamel wear (sd) for the whitening toothpaste and the standard
      silica toothpaste after four weeks was 0.20 (0.11) and 0.14 (0.10); after 8 weeks
      was 0.44 (0.33) and 0.18 (0.17), and after 12 weeks was 0.60 (0.72) and 0.67
      (0.77) microns respectively. After four, eight and twelve weeks, the difference
      in enamel wear between the two toothpastes was not of statistical significance (p
      > 0.05, 2 sample t-test) at any time point. CONCLUSIONS: The whitening toothpaste
      did not give a statistically significantly greater level of enamel wear as
      compared to a standard silica toothpaste over a 4-, 8- and 12-weeks period.

PMID- 16296259
TI  - Reduction of oral levels of volatile sulfur compounds (VSC) by professional
      toothcleaning and oral hygiene instruction in non-halitosis patients.
AB  - PURPOSE: The aim of the study was to determine the longitudinal effect of an oral
      hygiene program on oral levels of volatile sulfur compounds (VSC). MATERIALS AND
      METHODS: The study subjects were randomly selected from patients attending a
      student course in operative dentistry and from staff members of our dental
      clinic. The test group (n = 30) received an oral hygiene training including
      professional toothcleaning (PTC), oral hygiene instruction, and motivation. The
      control group (n = 10) received no particular treatment. None of the subjects
      suffered from bad breath nor performed regular tongue cleaning. At baseline,
      immediately after PTC, one week, and four weeks thereafter we measured the oral
      hygiene status by means of the papillary bleeding index (PBI) and the oral
      concentrations of VSC by using a portable sulfide monitor (Halimeter). RESULTS:
      Immediately after PTC, as well as one week, and four weeks after entering the
      program the PBI and the VSC-levels were significantly decreased as compared to
      the baseline values and the control group. VSCs were decreased by 34.9% (+/- 6.3)
      after PTC, 33.2% (+/- 7.1) one week, and 27.9% (+/- 5.8) four weeks thereafter.
      CONCLUSION: The present study shows that in a group of patients without bad
      breath, an oral hygiene training program including professional toothcleaning,
      motivation and instruction of self-applied oral hygiene procedures is capable of
      reducing both papillary bleeding and oral levels of VSC Halimeter readings over
      the observation period of four weeks.

PMID- 16296260
TI  - Commentary: are care guidelines useful in community-acquired pneumonia? Value
      hinges on improving outcomes.

PMID- 16296261
TI  - Pneumonia in older adults. New categories add complexity to diagnosis and care.
AB  - The microbiology of community-acquired pneumonia (CAP) in older adults,
      particularly in residents of long-term care facilities, differs from that in the
      general US population. Respiratory syncytial virus (RSV) and human
      metapneumovirus (HMPV) are important, newly appreciated causes of pneumonia and
      triggers of comorbid disease exacerbations that often lead to hospitalization of
      high-risk elderly patients with underlying heart or lung disease. Here, Dr High
      examines the diagnostic and treatment strategies that are needed in older adults
      and outlines preventive methods that may greatly reduce the risk of illness in
      this population.

PMID- 16296262
TI  - Update on community-acquired pneumonia. New pathogens and new concepts in
      treatment.
AB  - Recent years have witnessed the emergence of new pathogens linked to community
      acquired pneumonia (CAP) along with new antibiotics designed to combat them. In
      this article, Dr Mandell presents an expert's view on these developments in the
      context of treatment guidelines for CAP. He also explores monotherapy versus
      combination therapy, the efficacy of rapid initiation of treatment, and short
      course therapy as a hedge against antimicrobial resistance.

PMID- 16296263
TI  - Treating atrial fibrillation. What is the consensus now?
AB  - Atrial fibrillation (AF) is a common cardiac arrhythmia, especially in elderly
      persons. Current recommendations outline pharmacologic and interventional
      therapies designed to minimize the risk of stroke and other morbidities that can
      accompany this condition. In this article, Drs Basu Ray and Heist review
      treatment options for cardioversion and control of rate and rhythm and make
      suggestions for best management in patients with chronic or intermittent AF.

PMID- 16296264
TI  - Is MS an auto-immune disease or a chronic gammaherpesvirus infection?
AB  - The geographical-epidemiological findings of MS over the past 75 years are
      reviewed. Evidence concerning PR latitude-gradients, clusters, migration
      patterns, and enhancement-protective factors are critically reviewed and
      analyzed. The evidence in genetics, twin-studies and auto-immune theories are
      also thoroughly scrutinized as to their possible involvement as causative factors
      in MS- and found to be somewhat lacking. Environmental discoveries in the Faroes
      and Key West clusters are reviewed for possible similar environmental causes by a
      deadly agent. Exogenous-environmental candidate agents over the past 35 years
      from measles to Marek's are reviewed and analyzed. The undisputed positive
      laboratory findings of MDV are discussed in relation to Bray's unusually high
      positive findings with EBV antigen and MS serums. The important discovery of HHV
      6 in oligodendrocytes of MS brains but not controls is considered and how this
      might relate to MDV. The conclusion is that genetics are indeed important in the
      natural resistance of individual immune systems to invading infectious agents
      (especially herpesviruses) but genetics in general have little to do with the
      pathogenesis of multiple sclerosis (but HHV-6, EBV, and MDV do).

PMID- 16296266
TI  - Elevated plasma RANTES levels in patients with atopic dermatitis.
AB  - Eosinophils and T cells are involved in the pathologic process of atopic
      dermatitis. To further understand the role of these cells, and the possible
      involvement of RANTES, in the pathogenesis of atopic dermatitis, we measured the
      plasma level of RANTES using the sandwich ELISA. The mean plasma level of RANTES
      in 11 patients with atopic dermatitis was significantly higher than that of 15
      normal control subjects. RANTES levels were higher in patients with severe form
      of atopic dermatitis than that of patients with mild disease. These findings
      suggest that RANTES may play a role in the recruitment and activation of
      eosinophils and T cells in atopic dermatitis.

PMID- 16296265
TI  - Amplified ELISA to detect autoantibodies to N-glycolyl-GM3 ganglioside.
AB  - Numerous immunochemical methods are now available for the detection of antibodies
      to gangliosides. An amplified ELISA method for detection of autoantibodies to
      NGcGM3 ganglioside in the sera of patients with various type of renal diseases
      was developed. IgM antibodies were found in 39 out of 53 sera of patients using
      30 normal healthy blood donor as a negative control. For human IgG conjugate no
      reactivity to NGcGM3 was seen in the sera. Positive ELISA results were confirmed
      by TLC-immunostaining using GM3, NGcGM3, NGcGM2 and Standard bovine gangliosides
      (GM1, GD1a, GD1b and GT1b). All sera were also assayed for reactivity with GM3 in
      ELISA to determine the line specificity of these antibodies. Based on these
      results, a protocol for a sensitive and reproducible amplification ELISA system
      for serum anti-NGcGM3 antibodies in patients with renal or other diseases is
      presented. The ELISA method described here in appear to be useful adjunt to
      measure antiNGcGM3 antibodies in sera of patients with various type of renal or
      other diseases.

PMID- 16296267
TI  - On the frontier.

PMID- 16296269
TI  - Disease management: modeling the future of health care.

PMID- 16296268
TI  - President Bush scores victory in House Patients' Bill of Rights debate. What's
      next?

PMID- 16296271
TI  - Health plans collaborate to tackle asthma.

PMID- 16296270
TI  - Plans vary disease management strategies.

PMID- 16296272
TI  - A day in the life of managed care: Health Alliance Plan's Medicare Appeals
      Specialist Yolanda Dodson.
AB  - Yolanda Dodson began working for Health Alliance Plan (HAP) as a high school co
      op student. Through 11 years in HAP's Claims and Claims Processing Departments,
      as well as six months spent as a telephone customer service representative, she
      developed a knowledge of managed care and customer service and gained valuable
      first-hand experience with members' concerns. Now Dodson is a Medicare Appeals
      Specialist, one of two staff people handling HMO and HAP Senior Plus (HAP's
      Medicare+Choice program) grievances and appeals. She serves as an "advocate for
      the member" as she investigates their cases within a tight mandatory deadline,
      recommends a resolution, and submits them for consideration to HAP medical
      directors. The following is a glimpse at one her typical days at HAP's Detroit
      offices.

PMID- 16296273
TI  - Employer team serves as health care watchdog. Verizon program gets seniors off
      dangerous drug.

PMID- 16296274
TI  - Creating the efficient health care marketplace.

PMID- 16296275
TI  - Listening: the first step toward healing.

PMID- 16296276
TI  - Saving antibiotic strength.

PMID- 16296277
TI  - Building a caring community. Coordinating the health care of children with
      special needs.

PMID- 16296278
TI  - Health care choices at menopause. Plan support helps women make educated
      decisions.

PMID- 16296279
TI  - E-health legal issues: a moving target.

PMID- 16296281
TI  - Playing with fire.

PMID- 16296280
TI  - E-mail: taming the monster.

PMID- 16296282
TI  - Patients' Bill of Rights debate: can President Bush break the logjam?

PMID- 16296284
TI  - Changing the lives of children with special needs through Medicaid managed care.

PMID- 16296283
TI  - A prescription for litigation disaster.

PMID- 16296285
TI  - View from a cancer center.
AB  - As part of Healthplan's genomics series, we have sought opinion and perspective
      from various sectors of health care. Articles in past issues have reflected both
      the enthusiasm and optimism of the genomics industry as well as the caution and
      concerns of health plan medical directors confronted with the question of who
      will pay for the new genetic services and treatments and--more importantly--how
      they will truly benefit patients. In this issue, we publish the perspective and
      goals of doctors and researchers at a renowned cancer center. As our series
      unfolds, it is becoming increasingly clear that a national dialogue is needed on
      the important questions raised by the authors in our genomic series. Readers are
      encouraged to send their views on this topic to Healthplan.

PMID- 16296286
TI  - Compassion for unidentified lives.

PMID- 16296287
TI  - If communication were easy, everyone would do it.

PMID- 16296288
TI  - An "interim" CEO leads a plan back to health.

PMID- 16296289
TI  - Looking for the needle in the haystack: techniques for finding high- and low-risk
      patients.

PMID- 16296291
TI  - Is IT bridging the 'cultural gap' between plans and physicians?

PMID- 16296290
TI  - Pharmacy benefit companies hone strategies to contain costs and improve quality.

PMID- 16296292
TI  - The role of ASPs.

PMID- 16296293
TI  - Seniors call for stronger Medicare+Choice program as basis for Medicare reform.

PMID- 16296294
TI  - Business takes on the job of improving health care.

PMID- 16296295
TI  - Making managed care work in California. Interview by Christopher J. Gearon.

PMID- 16296296
TI  - Volunteering to meet the needs of the community. AAHP partners with Los Angeles
      Mission to host Health Fair for the Homeless.

PMID- 16296297
TI  - Question Medicare: but can you ignore it? The well-managed health plan has a
      Medicare strategy.

PMID- 16296298
TI  - Social HMOs: an answer for an aging population.

PMID- 16296299
TI  - Building a scientific foundation for prevention.

PMID- 16296300
TI  - What if it were your mother?

PMID- 16296301
TI  - Equal access to quality health care. Techniques for understanding cultural
      diversity lead to better treatment, outcomes.

PMID- 16296302
TI  - Changing lifestyles to combat osteoporosis.

PMID- 16296304
TI  - Implementing an employee portal. Taking steps toward a "paperless" future.

PMID- 16296303
TI  - Arbitration: a "win-win" for consumers and health plans.

PMID- 16296306
TI  - Not for sale.

PMID- 16296305
TI  - Plan websites: building traffic.

PMID- 16296307
TI  - The importance of using mouthguards.

PMID- 16296308
TI  - Nicotine-puffing moms can harm future generations.

PMID- 16296309
TI  - More periodontal health benefits discovered.

PMID- 16296311
TI  - Oral health for people with special needs: consensus statement on implications
      and recommendations for the dental profession.
AB  - In November 2004, the Pacific Center for Special Care at the University of the
      Pacific Arthur A. Dugoni School of Dentistry, with support from the California
      Dental Association Foundation, hosted a conference to explore the issue of oral
      health for people with special needs. This conference was held in conjunction
      with the joint meetings of Pacific's Statewide Task Force on Oral Health for
      People With Special Needs and Pacific's Statewide Task Force on Oral Health and
      Aging. These groups of interested stakeholders meet several times a year to
      discuss the increasing problems faced by people with disabilities, elderly
      individuals, and other special populations in obtaining access to oral health
      services and maintaining good oral health. The purpose of this conference was to
      explore the changing population of people with special needs, analyze the
      implications for the dental profession and society, and describe systems and
      strategies that might lead to improved oral health for these populations. This
      conference also served as a forum for developing oral health recommendations as a
      part of the California Commission on Aging's Strategic Plan for an Aging
      Population. Seven nationally recognized speakers presented draft papers on
      various aspects of this topic. These presentations are published as the
      additional papers in this and the next issue of the Journal. There was time for
      audience reaction and discussion with the speakers. The speakers and a designated
      group of reactors then developed this consensus statement and recommendations for
      addressing these issues.

PMID- 16296313
TI  - Improving oral health disparities and access to care: challenges and
      opportunities for the states.
AB  - States and their dental reimbursement, practice, and education policies and
      programs have done little to address oral health disparities. Particular state
      policies and programs are often cited as having an adverse impact on oral health
      access for vulnerable populations. These include poor Medicaid and State
      Children's Health Insurance Program reimbursement, an inadequate safety net, the
      ban on the corporate practice of dentistry, and a lack of funding to prepare the
      dental workforce to treat special needs populations and provide culturally
      competent care. (The State Children's Health Insurance Program, created by the
      Balanced Budget Act of 1997, enacted Title XXI of the Social Security Act and
      allocated about dollar 20 billion over five years to help states insure more
      children.) While state health officials have paid less attention to oral health
      disparities, there has been increased interest by state policymakers in
      addressing the special health care needs of the elderly, disabled, and children.
      These include state responses to the 1999 Olmstead Supreme Court decision and
      state pharmaceutical assistance programs for the elderly and disabled. (In
      rejecting the state of Georgia's appeal to enforce institutionalization of
      individuals with disabilities, the Supreme Court in 1999 affirmed the right of
      individuals with disabilities to live in their community in its 6-3 ruling
      against the state of Georgia in the case Olmstead v. L.C and E.W.) However, a few
      states have begun to develop solutions to explicitly address oral health access
      problems. States are considering or testing the following programs and policies
      pertaining to 1) improving workforce supply and distribution, 2) education reform
      and increased public accountability, 3) practice reform, and 4) increased data
      collection and research.

PMID- 16296312
TI  - New models for improving oral health for people with special needs.
AB  - The number of people with special needs is increasing dramatically. In this
      context, people with special needs refer to people who have difficulty having
      good oral health or accessing oral health services because of a disability or
      medical condition. Among these groups, the number of people with developmental
      disabilities and the emerging population of aging "baby boomers with teeth" are
      demonstrating dramatic growth. People in these groups have significantly more
      dental disease than the general population. It is already difficult to impossible
      for many people with special needs to obtain oral health services. Under the
      current system of care, this situation will only get worse. The characteristics
      of a new model, which can better address the oral health problems of people with
      special needs, are described.

PMID- 16296314
TI  - The Minnesota Oral Health Care Solutions Project: implications for people with
      special needs.
AB  - Disparities in oral health status and access to dental care are major problems
      for people with special needs in Minnesota and across the country. The current
      delivery system for people with special needs is failing. Patients, community
      leaders, private dentists, safety net clinics, and state agencies are frustrated
      with the Medicaid program that funds the current system; and everyone is looking
      for new solutions. What would an improved oral health care system and Medicaid
      model look like? This paper describes Minnesota's Oral Health Care Solutions
      Project that seeks to answer this question and highlights the implications of a
      new model for people with special needs. The low reimbursements and
      administrative burdens of Minnesota's Medicaid program have led many dentists to
      reduce or stop seeing public program patients. As a result, many people with
      special needs have been unable to obtain routine dental care and therefore seek
      treatment in emergency rooms.

PMID- 16296316
TI  - [Prospect and retrospect on protein phosphatase research].

PMID- 16296317
TI  - [Various physiological functions of protein tyrosine phosphatase receptor type Z
      (Ptprz)].

PMID- 16296318
TI  - [Helicobacter pylori CagA and SHP-2 tyrosine phosphatase].

PMID- 16296319
TI  - [Regulation of stress-activated signal pathways by protein phosphatase 2C].

PMID- 16296321
TI  - [Cell regulation through calcineurin signalling].

PMID- 16296320
TI  - [Regulation of the immune system by protein tyrosine phosphatases].

PMID- 16296322
TI  - [SHP tyrosine phosphatases and a novel cell-cell signaling system].

PMID- 16296323
TI  - [Function and regulation of Ser/Thr-specific protein phosphatase-1 (PP1)].

PMID- 16296324
TI  - [Protein phosphatases that regulate multifunctional Ca2+/calmodulin-dependent
      protein kinases].

PMID- 16296325
TI  - [MKP-7 and LDPs as new members of dual-specificity protein phosphatases].

PMID- 16296326
TI  - [Comparison of four rapid diagnostic kits using immunochromatography to detect
      influenza B viruses].
AB  - We compared the usefulness of 4 rapid influenza diagnostic 1-device kits using
      immunochromatography, which facilitate type differentiation, i.e. ESPLINE
      Influenza A&B-N (Fujirebio Corp., Japan: ESPLINE), POCTEM INFLUENZA A/B (Sysmex
      Corp., Japan: POCTEM), Quick Vue Rapid SP influ (Quidel Corp., U.S.A.: Quick
      Vue), and Capilia Flu A + B (TAUNS Corp., Japan: Capilia), in 278 children in
      whom influenza infection was suspected in 2004 and 2005. Nasopharyngeal aspirates
      were diluted for virus isolation and residual samples were centrifuged. Using the
      supernatant, we conducted rapid diagnosis testing. Influenza virus AH3 was
      isolated from 40 children, and influenza B virus from 163. Of the 40 children,
      the sensitivity and specificity of ESPLINE, POCTEM, Quick Vue, and Capilia were
      100%/100%, 95%/100%, 98%/96%, and 98%/96%. In the 163 children, the sensitivity
      and specificity were 89%/100%, 87%/100%, 88%/97%, and 86%/98%. ESPLINE showed the
      highest sensitivity and specificity to influenza viruses AH3 and B. All kits were
      less sensitive to influenza B virus than to influenza A virus, however. The
      specificity of Quick Vue and Capilia was low; so these kits must be improved.

PMID- 16296327
TI  - [Investigation on cognition of zoonosis among veterinary clinical staff].
AB  - We conducted a survey to determine how much veterinary clinic staff, including
      veterinary surgeon and veterinary technicians, know about zoonosis. Response was
      52.5%. All staff members knew of zoonosis. Staff members who knew what zoonosis
      meant accounted for 98%. Staff members trained in zoonosis accounted for 75%
      among veterinary surgeons and 66% among veterinary technicians. Staff members who
      thought that zoonosis would increase in future accounted for 92% among veterinary
      surgeons and 79% among veterinary technicians. Staff members who were asked by
      pet owners about zoonosis accounted for 87% among veterinary surgeons and 51%
      among veterinary technicians. Staff members who thought veterinary surgeons must
      report zoonosis to public health centers accounted for 96% among veterinary
      surgeons and 88% among veterinary technicians. Veterinary clinic staffs thus had
      correct knowledge and were aware of zoonosis. The network of medical staff and
      veterinary staff could therefore build on this result.

PMID- 16296328
TI  - [A case of nonclostridial gas gangrene of the leg complicated by severe
      pneumonia].
AB  - A 73-year-old man admitted for febrile left leg pain with dyspnea, who had poorly
      controlled diabetes was found on admission to have severe hypoxia and chest X-ray
      showed infiltrates in the middle to lower left lung. X-rays of the left leg
      showed gas around the knee joint. These findings suggested severe pneumonia with
      gas gangrene, necessitating immediate debridement of the gas gangrene lesion and
      hyperbaric oxygenation. Antibiotics were also administered intravenously
      (panipenem/betamipron 0.5 g x 3/day, clindamycin 600 mg x 2/day, and erythromycin
      500 mg x 3/day). We conducted fiberoptic bronchoscope daily because consolidation
      of the whole left lung developed with purulent sputum expectoration. Both
      pneumonia and gas gangrene gradually ameliorated avoiding amputation of theleg.
      Gas gangrene was cured without leaving sequelae such as motor dysfunction.
      Staphylococcus aureus was detected in both pus from the leg and sputum collected
      by bronchoscopy. Microorganisms showed the same pattern of sensitivity to
      antibiotics, suggesting a causal relationship between pneumonia and gas gangrene
      through the blood stream. Gas gangrene was considered the primary infection
      followed by pneumonia, since pain and swelling of the left leg preceded the
      airway symptoms. The present case illustrates in compromised hosts including
      diabetics, gas gangrene may develop taking an opportunity of airway infection,
      and that in some cases, early debridement of the lesion and optimal use of
      antibiotics may help cure this disease without aggressive surgery. Hyperbaric
      oxygenation may also be useful, although its validity must be investigated
      further.

PMID- 16296329
TI  - [Prevalence of hepatitis B and C virus markers in patients with hepatocellular
      carcinoma and outpatients with liver dysfunction in Mongolia].

PMID- 16296330
TI  - [Determination of antibody titer to Bartonella henselae by indirect fluorescence
      antibody assay using B. henselae from domestic cats as antigen].

PMID- 16296331
TI  - [Micrococcus blood stream infection in patients receiving epoprostenol].

PMID- 16296332
TI  - [A clinical isolate of Leclercia adecarboxylata from a patient of
      pyelonephritis].

PMID- 16296333
TI  - Nonrandom chromosomal numerical abnormality as a new molecular cytogenetic tumor
      marker--a retrospective study of 60 gastric cancer cases.
AB  - Chromosomal numerical abnormality (CNA) is one of the distinct characteristics of
      human cancers, though the mechanisms and tumor specificity of this phenomenon
      have not been adequately analyzed. Recently, we developed a new sensitive
      fluorescence in situ hybridization (FISH) method that involves short-term
      microwave (MW) treatment for hybridization. In this study, we applied this
      modified FISH technique to investigate the CNA of 60 gastric cancer cases with a
      panel of 18 chromosome-specific alpha-satellite probes (for chromosome 1-4, 6-12,
      15-18, 20, X, and Y) and region-specific probes (c-myc, p53, and Her-2/neu) to
      enumerate the respective chromosome numbers in interphase nuclei of formalin
      fixed paraffin-embedded sections. The numerical aberrations of chromosome 1, 3,
      8, 17, 20, and X were frequent regardless of histologic types, whereas
      aberrations of chromosomes 10, 15, and 18 occurred less frequently (p<0.001).
      From a histopathological standpoint, the mucocellular type of carcinoma had
      stable CNA in comparison with the tubular type of carcinoma (21.7+/-9.63% vs.
      58.3+/-12.32%, p<0.001) and, of note, there was less extensive CNA in female
      cases. A dramatic difference in patient outcome was detected according to the
      involvement of chromosomes 3, 10, 11, 12, 17, and Y; cases with CNA of these
      chromosomes had a worse prognosis (p<0.001). A two-step analysis of the CNA of 6
      chromosomes and locus specific gene abnormalities successfully divided gastric
      cancer cases into those with a good outcome and those with a poor outcome. This
      analysis allows one to more accurately predict prognosis than by using a simple
      classification based on conventional clinicopathological diagnosis.

PMID- 16296334
TI  - [Role of clinical laboratory in Japanese general hospital for equilibrium
      functional tests].
AB  - Recent automation in clinical laboratories affords healthcare providers with
      numerous options in terms of physiological tests. However, the role of the
      clinical laboratory in the field of equilibrium functional tests is not clearly
      defined. Therefore, we conducted a questionnaire survey to define the role of
      clinical laboratories in general hospitals. We present the results of our
      investigation and the approach employed by the clinical laboratory of our
      hospital. Rates of healthcare providers desiring the conduct of equilibrium
      functional tests by clinical laboratories were 78% and 70% in otolaryngology and
      neurosurgery departments, respectively; moreover, 92% of technologists from
      clinical laboratories responded that an equilibrium functional test can be
      performed upon request. Furthermore, 84% of clinical laboratory staff members and
      77% of staff from neurosurgery departments agreed that implementation of a system
      allowing each department to request equilibrium functional tests from the
      clinical laboratories is necessary. This finding was indicative of the high
      demand for equilibrium functional tests by clinical laboratories. Therefore,
      equilibrium functional tests offered by clinical laboratories not only reduce the
      workload of the otolaryngology department, but also result in a major
      contribution with respect to management of the entire hospital in terms of high
      quality examination findings and allocation of healthcare providers in other
      departments.

PMID- 16296335
TI  - [Fragmented red cells are the major cause of spuriously high platelet counts in
      patients with fragmented red cells when counts are obtained by automated blood
      cell counter].
AB  - Platelet counts measured by automated blood cell counter often show spuriously
      high values when measuring samples contain particles of equal size to platelets.
      The major cause of spuriously high platelet counts in samples with fragmented red
      cells (FRC) is thought to be the FRC themselves. We studied the correlation
      between FRC and spuriously high platelet counts in 40 patients demonstrating FRC
      on blood smears. FRC were measured by manual hemocytometry and by flow cytometry
      using a monoclonal antibody against glycophorin A (GPA method). There was a
      significant correlation between spuriously high platelet counts and FRC by manual
      hemocytometry (r=0.60, p<0.001) or FRC by the GPA method (r=0.45, p<0.005). These
      data suggest that FRC are the major cause of spuriously high platelet counts in
      samples with FRC.

PMID- 16296336
TI  - [Side effects of phlebotomy: pathophysiology, diagnosis, treatment and
      prophylaxis].
AB  - Although phlebotomy is on the whole a safe procedure, the frequency of side
      effects being low and their severity weak, there have still been rare incidents
      of serious accidents such as nerve injury, vasovagal reaction and infections.
      Medical staff performing phlebotomy must be aware of the pathophysiology of these
      side effects, be careful in avoiding them, and be trained to properly treat them.
      Nerve injury is the complication of which phlebotomists should take the greatest
      caution. It sometimes causes permanent motor and/or sensory nerve dysfunction of
      arms and hands. Appropriate selection of vein and careful procedure of
      venipuncture are required. Vasovagal reaction is a relatively common complication
      causing hypotension, palor and occasional syncope. For emergency cases, a bed,
      oxygen tanks, and a utility cart with drug supplies should be provided in the
      phlebotomy room. Infections, especially those by blood-borne pathogen, are rare
      but serious complications. When performing evacuated tube venipuncture procedure,
      blood collecting tubes sterilized on the inside and single-use holders must be
      used to avoid infections through backflow of blood. Phlebotomists must follow the
      procedure presented in the guidelines to avoid backflow. Hematoma, allergy,
      hyperventilation, air embolism, anemia and thrombosis are other side effects
      occasionally caused by phlebotomy. Finally, medical staff should recognize that
      sincere communication with patients receiving phlebotomy is essential and efforts
      to inform them of the possibility of these side effects are becoming increasingly
      necessary in the current medical environment.

PMID- 16296337
TI  - [JCCLS phlebotomy standards].
AB  - In 2004, the Japanese Committee of Clinical Laboratory Standards (JCCLS)
      published a standard phlebotomy guideline, which not only ensures the safety of
      the patients and phlebotomists but is adopted to the healthcare setting in Japan.
      This phlebotomy standard is also essential for the standardization of clinical
      laboratory tests. This guideline was completed on the basis of current phlebotomy
      procedures widely in use in Japan using phlebotomy standards in the USA as
      references, while reconsidering their scientific reasoning as far as possible. At
      the same time, factors such as practicality and cost benefit were taken into
      account. The content of the guideline includes necessary facilities and
      equipment, a step by step safe but practical venipuncture procedure, an
      explanation of the individual steps, and other supplementary information such as
      alternative methods. The first edition, published as tentative guideline, is
      planned to be revised after a set period of time based on the comments and
      suggestions from a wide range of people concerned, so that it can be published as
      an approved guideline.

PMID- 16296338
TI  - [Issues of blood collection using evacuated tubes and needle holders].
AB  - Upon collecting venous blood using evacuated tubes without sterilization, some
      operation procedures for tourniquets are increasing the risk for bacterial
      infection by back flow from tube to vein. This fact was widely indicated in 2003
      and safety for blood collection was getting more and more recognition in Japan,
      although reported in Canada and U.S. about 30 years ago. Thereafter, the MHLW
      (Ministry of Health, Labor and Welfare) ordered blood collection tube
      manufacturers to revise directions for use in their package inserts--A tourniquet
      should be released before inserting a tube into a holder. It was followed by
      obligation of sterilization of all evacuated blood collection tubes.
      Concurrently, JCCLS (Japanese Committee for Clinical Laboratory Standards)
      examined safety of patients and healthcare workers, assurance of correct test
      results, practicality and so on and issued the Guideline for Standard Procedure
      of Blood Collection 1st Edition. It recommends changing a holder every patient
      and then throwing it away into a disposal container keeping the needle with the
      holder in order to prevent cross infection. In 2005, MHLW ordered manufacturers
      to revise package insert again, in consideration of responses of healthcare field
      such as launching the sale of single use holders or issuing the guideline. If
      sterilized tubes, single use holders, and needles with pressure-resistant rubber
      sleeve are used all together, tourniquets can be applied during blood collection.

PMID- 16296339
TI  - [Current state and problem of collecting blood--from medical technologists
      standpoint].
AB  - Blood collection is indispensable, but discussion over proper blood collection
      methods became active after a problem occurred in both the collecting method and
      the blood collection tube itself, during vacuum blood collection. In Japan there
      has been no standard blood collection method until now, and it has been executed
      based on individual facilities, guidelines, or on individual experience.
      Regarding these points, the Japanese Committee on Clinical Laboratory Standards
      (JCCLS) created the 1st edition of guidelines based on National Committee on
      Clinical Laboratory Standards (NCCLS) in July 2004, and this has been used until
      now. Here I would like to describe current issues of collecting blood from the
      point of view of medical technologists.

PMID- 16296340
TI  - [Present conditions and problems about drawing blood].
AB  - The problem of clinical on-site confusion was put to the Japanese nursing
      association (JNA) safety measures department after a notice about "Self
      inspections and Other Precautions for the Use of Vacuum Blood Collection Tubes"
      from the Ministry of Health, Labor and Welfare in November, 2003. The Infection
      Control Network in Japan (ICNJ) investigated the situation regarding the use of
      vacuum blood collection tubes and their cause of medical on-site confusion, in
      February, 2004. Results were obtained from 90 Healthcare facilities (collection
      rate 91%). The majority had more than 500 beds, and all Healthcare facilities
      knew of the notice from the Ministry of Health, Labor and Welfare. The results
      expressed the present conditions of the institutions, where information releases
      such as notices of the Ministry of Health, Labor and Welfare were provided.
      However, following the notice from the Ministry of Health, Labor and Welfare
      concerning the processing method using a drawing blood holder, and the
      disinfection method, 30% of Healthcare facilities reported on-site confusion
      concerning various things. Confusion existed in the processing method/procedure,
      and there were problems with the increase in the number of duties and
      administration of the drawing blood holders method, so a guarantee of the
      effectiveness of disinfection was difficult.

PMID- 16296341
TI  - [Recent progress of catecholamines--mainly focusing on metabolic syndrome].
AB  - Although catecholamine is a well-known classical hormone, its precise
      pathophysiological role remains obscure. Recently, growing evidence suggests that
      this hormone plays a causative role in several common diseases such as
      hypertension, diabetes, and dyslipidemia (metabolic syndrome). Thus, the
      discussion that follows will mainly focus on our data, including: 1) leptin as
      well Ang II subtype-2 receptor (AT2), assumed to be a key molecule for metabolic
      syndrome, much involved in regulating catecholamine synthesis and secretion. 2)
      Recent progress of pheochromocytoma (SDHX and Peptidergic Regulation). 3)
      Chromogranin A, as a possible marker for chronic sympatho-adrenal activities.

PMID- 16296343
TI  - [Regulation of insulin sensitivity by subcellular GLUT4 targeting].
AB  - SUMO conjugating enzyme Ubc9 has been shown to upregulate GLUT4 in muscle cells
      although the mechanism of action is unknown. We investigated the physiological
      significance of Ubc9 in GLUT4 turnover and subcellular targeting by adenovirus
      vector-mediated overexpression and by siRNA-mediated gene silencing of Ubc9 in
      3T3-L1 adipocytes. Overexpression of Ubc9 resulted in inhibition of GLUT4
      degradation and promotion of its targeting to the non-endosomal, non-TGN GLUT4
      storage vesicles (GSV), leading to an up-regulation of GLUT4 expression level and
      insulin-responsive glucose transport. While long-term insulin stimulation caused
      GLUT4 down-regulation by 40-50%, which was inhibited with lysosomal inhibitors
      and was associated with a selective reduction in GLUT4 in GSV, overexpression of
      Ubc9 antagonized these long-term effects of insulin. By contrast, Ubc9 gene
      silencing with siRNA caused a marked decrease in the GLUT4 level, whereas
      overexpression of the catalytically inactive mutant of Ubc9 increased GLUT4 and
      insulin-stimulated glucose transport to the level comparable to that with wild
      type Ubc9. These results suggest that Ubc9 up-regulates GLUT4 by inhibition of
      lysosomal sorting and promotes GLUT4 targeting to GSV by a mechanism unrelated to
      its catalytic activity. Thus, Ubc9 plays an indispensable role in the expression
      and maintenance of the insulin-sensitive glucose transport system in adipocytes.

PMID- 16296342
TI  - [Thyroglobulin gene abnormalities].
AB  - Congenital hypothyroidism is caused either by abnormal development of thyroid
      glands or by inborn errors of thyroid hormone synthesis. Thyroglobulin mutations
      which caused overt Cretins with physical and mental development impairment were
      once believed rare. However, since the discovery of mild hypothyroidism due to
      thyroglobulin mutations, 54 cases from 43 families were identified in Japan. The
      patients presented either transient elevation of serum TSH during infancy or
      growing giant goiters from childhood. Among 15 patients who were born after
      initiation of neonatal screening in 1979, 13 patients were identified by high
      serum TSH. In contrast, the major manifestation in patients born before 1979 is
      persistent growth of goiters with euthyroidism or subclinical hypothyroidism.
      Among 25 mutations, Cys1264Arg and Cys1077Arg are hot spots. The Cys1264Arg
      patients were found all over Japan, but the Cys1077Arg patients were confined to
      a small village of a southern island in Japan. The occurrence of the
      thyroglobulin mutations in the general population is 1/67,000. The pathogenesis
      of abnormal thyroglobulin is defective intracellular transport. The histological
      findings include empty colloid in the follicles and distended ER filling the
      entire cytoplasm of the thyrocytes. An in vitro expression study showed that
      abnormal thyroglobulin was not secreted from cultured cells. Because of
      persistent growth of the thyroid, 25 patients underwent surgical treatment. Among
      them, 11 patients suffered from thyroid cancers, most of which were of the
      papillary type. We found two BRAF activating mutations Val599Glu and Cys600Gln in
      five patients tested. In conclusion, we found many patients with thyroglobulin
      mutations in Japan. They were found by high serum TSH at neonatal screening or
      persistent growth of goiters in adults. Surgical treatments were inevitable, and
      40% of the removed thyroids contained thyroid cancers, some of which were caused
      by activating mutations of the BRAF gene.

PMID- 16296344
TI  - [Studies on HIV/AIDS using the fission yeast Schizosaccharomyces pombe].
AB  - Human immunodeficiency virus (HIV) is a causative agent of acquired
      immunodeficiency syndrome (AIDS) and a member of Retrovirus family. The name of
      "retrovirus" is said to be derived from "reverse-transcribing oncogenic virus."
      Living up to its name, retrovirus has contributed to oncology, especially in the
      field of cancer pathogenesis. Retrovirus research has led to discovery of a
      number of oncogenes as well. Since the discovery of HIV in 1983, however,
      retrovirus has also been considered as an important etiologic agent that could
      incapacitate the cells involved in immune responses. As of the end of 2004, the
      number of people living with HIV/AIDS is estimated to be as large as 40 million.
      Every year, nearly 5 million people are newly infected with HIV, and 3 million
      people die of AIDS in the world, mainly in Africa and southeastern and southern
      Asia. Despite extensive studies, detailed mechanisms of HIV pathogenesis are
      still unclear, and efforts are being made to clarify functions of various HIV
      proteins and identify the cellular factors that could interact with the HIV
      proteins. One of the HIV accessory proteins, Vpr, causes the host cell cycle
      arrest at G2 phase, which may play an important pathogenic role in AIDS
      induction. Exploiting the fission yeast Schizosaccharomyces pombe useful for cell
      cycle studies, I've been trying to elucidate the mechanism by which Vpr induces
      the G2 arrest as presented in this review.

PMID- 16296345
TI  - [Preventive medicine and diagnostic testing].

PMID- 16296346
TI  - [The convention on the rights of the child: respect for individuals].

PMID- 16296347
TI  - [A boy with a peculiar face and degenerative course].

PMID- 16296348
TI  - [Prospective study of first unprovoked seizure].
AB  - We prospectively examined the natural history of children who suffered a first
      unprovoked seizure (FUS). Forty-five children who suffered a seizure without any
      detectable precipitating factors were enrolled in this study. Absence seizure,
      myoclonic seizure, and epileptic spasms were excluded from this study. They were
      followed for at least 2 years without anti-epileptic medications in 43 cases (2
      were given drugs). Thirty patients (66.7%) had another seizure during follow up.
      Of the 30 patients with recurrence, 11 suffered the second seizure within 1
      month, 19 within 3 months, 24 within 6 months, 26 within 1 year, and 30 within 2
      years. Occurrence of generalized convulsions, a past history and family history
      of febrile seizures, epileptic discharges on the EEG (especially a diffuse
      pattern), and developmental delay prior to the FUS were risk factors for seizure
      recurrence. Up to one third of the patients had no more recurrent seizures during
      the next 2 years, so it seems reasonable to follow FUS patients without
      medication.

PMID- 16296349
TI  - [Subacute encephalitis/encephalopathy with residual cognitive deficit].
AB  - We studied clinical features of 5 patients with subacute
      encephalitis/encephalopathy with residual cognitive deficit. In all patients,
      impairment of consciousness was mild at the onset, progressed between 4 and 15
      days after the onset, and reached its peak at 6-18 days after the onset.
      Neuroradiological or electrophysiological examinations at the onset showed normal
      or mildly abnormal findings. In accordance with the clinical deterioration, brain
      atrophy was detected on cranial magetic resonance imaging (MRI) in 3 patients,
      and electroencephalogram revealed slowing of the background activities in all
      patients. Single photon emission computed tomography (SPECT) showed hypoperfusion
      in the fronto-temporal areas in all patients at the recovery stage. Three
      patients had severe mental deficits, and the other two had mild cognitive
      deficit. Motor impairment was observed in one patient.

PMID- 16296350
TI  - [Complications of tracheostomy in patients with severe motor and intellectual
      disabilities and their management].
AB  - Some patient with severe motor and intellectual disabilities have a narrow
      mediastinum due to severe scoliosis or thoracic deformity. Complication of
      tracheostomy in these patients, such as granulation of the lower end of the
      cannula and tracheo-innominate artery fistulae, are difficult to treat. The
      causes of recurrent respiratory distress after tracheostomy in four patients with
      severe motor and intellectual disabilities were investigated, and its management
      was evaluated based on chest CT and bronchoscopy. In all patients, the lower end
      of the cannula was in contact with the site of tracheal stenosis, accompanied by
      granulation with arterial pulsation. In three patients, tracheomalacia as a
      complication of tracheostomy was also noted. In three patients, changing the
      cannula to fix its lower end proximally to the lesion, combined with stent
      placement in one patient with tracheomalacia, resulted in regression of the
      granulation and respiratory distress. However, one patient with severe
      tracheomalacia, who had been treated by stent placement alone, died of tracheo
      innominate artery fistula. To prevent complications of tracheostomy in patients
      with severe motor and intellectual disabilities, it is important to select
      cannulas with a suitable length and angle. In the absence of severe
      tracheomalacia, use of custom-made short cannulas that can be fixed proximally to
      the site of stenosis and to the proximity of arteries are appropriate for this
      purpose.

PMID- 16296351
TI  - [Developmental changes in the Collis horizontal reaction analyzed using a three
      dimensional video motion analysis system. I. Examination of techniques for
      inducing Collis horizontal reaction].
AB  - We used a three-dimensional video motion analysis system to evaluate techniques
      for inducing the Collis horizontal reaction in 46 infants (total 217 times) from
      1-9 months old. Additionally, we examined the safety of different techniques for
      inducing the Collis horizontal reaction in 20 infants (total 66 times), from 1-3
      months old, 40 times by holding the shoulder joint and 26 times by not holding
      the shoulder joint. Regardless of who performed the examination, the average
      height that induced the reaction increased from 24.3 to 34.6 cm and the average
      speed of reaction increased from 28.2 to 43.4 m/s as the age of the infants
      increased. Additionally, when the Collis horizontal reaction was induced in
      infants 1-3 months old by holding the shoulder joint of infants, the average fall
      angle of the head was 7.291 degrees and was not significantly larger than when
      the reaction was induced by not holding the shoulder joint, which resulted is an
      average fall angle of the head was 19.302 degrees. However, although the average
      speed to support the body increased, the fall angle of the head did not increase
      when the shoulder joint was held. The Collis horizontal reaction is usually not
      performed in early infancy before head control is acquired, because of the burden
      to neck caused by the fall of the head and the excess expansion of shoulder joint
      capsule. However these results suggest that when performing the Collis horizontal
      reaction in early infancy before head control is acquired, the Collis horizontal
      reaction can be safely performed by holding the shoulder joint, regardless of the
      skill of the diagnostician. Therefore, the Collis horizontal reaction is an
      excellent method to assess infant development, and can be performed at the usual
      infant health examinations.

PMID- 16296352
TI  - [Developmental changes in the Collis horizontal reaction analyzed using a three
      dimensional video motion analysis system. II. Examination of upper-limb movement
      during the Collis horizontal reaction].
AB  - At four months old, infants of 72% challenged with the Collis horizontal reaction
      touch the floor with the back of their free hand. As the infants grow older, the
      ratio of infants that open their free hand and perform a support reaction
      increases from 0% to 100%. At nine months old, all infants perform this support
      reaction with their free hand palm-side down. To assess infant development more
      accurately, we used a three-dimensional video motion analysis system to evaluate
      upper limb movement in 38 infants (total 151 times) from 4-9 months old during
      the second and third phases determined by the Collis horizontal reaction. By
      analyzing the constituent components of upper limb movement during the Collis
      horizontal reaction, we assessed the usefulness of the reactions as an objective
      tool to measure developmental changes in infants. During the analysis, we thought
      to assess the speed of the upper limb reaction was respect to pronating the
      forearm, supporting the body with the palm down, and location of their free hand.
      The analysis shows that if development progresses normally and infants pronate
      the forearm to support the body with the palm down, the central value at which
      their free hand is located moves to a point under the shoulder. The results
      suggest that in infants four to nine months old, the Collis horizontal reaction
      is an excellent method to assess not only the present physical development level,
      but also future physical development attainment by only evaluating developmental
      changes of upper limb movement only.

PMID- 16296353
TI  - [Low-dose therapy with carbamazepine for convulsions associated with mild
      gastroenteritis].
AB  - We investigated the effect of carbamazepine on convulsions associated with mild
      gastroenteritis. Sixteen infants and young children (aged 9 months to 3 years)
      who experienced repetitive convulsions associated with mild gastroenteritis were
      admitted to our hospital. We treated the sixteen affected patients with 5 mg/kg
      of carbamazepine once per day until the diarrhea had stopped. Thirteen of the
      sixteen patients were subjected to intravenous and/or suppository administration
      of diazepam (0.3-0.5 mg/kg/time), and one patient suppository administration of
      0.5 mg/kg diazepam and 5.7 mg/kg phenobarbital before the administration of
      carbamazepine. In all patients who were given diazepam and/or phenobarbital, the
      convulsions recurred after the administration of these medicines. The convulsions
      occurred 2 to 8 times (mean, 4.1 times) before the administration of
      carbamazepine. Fifteen of the sixteen patients had no seizures after the
      administration of carbamazepine. One patient had one convulsion 15 min after the
      administration of carbamazepine. All patients were treated with 5 mg/kg of
      carbamazepine once per day until the diarrhea had stopped, i.e. for 2 to 9 days
      (mean, 6.4 days). Low dose therapy with carbamazepine once per day is thus
      effective for convulsions associated with mild gastroenteritis.

PMID- 16296354
TI  - [Usefullness of bronchofiberscopy for difficult intubation in patients with
      severe motor and intellectual disabilities].
AB  - In 21 patients with severe motor and intellectual disabilities, bronchofiberoptic
      intubation was performed because of difficulty in tracheal intubation by direct
      laryngoscopy. The patients ranged from 3 to 35 years old (mean age: 20.2 years).
      Twenty patients (95.2%) were bedridden. Among the 21 patients, 15 had cerebral
      palsy and 20 had hypertonia. The reason for intubation were acute respiratory
      failure due to pneumonia in 17 cases, suffocation after aspiration of food in 2
      cases, hypovolemic shock in 1 case, and laryngotracheomalacia in 1 case.
      Intubation was done pernasally in 15 patients and perorally in 10. It was
      successful in 20 cases without any significant complications. The Cormack score
      ranged from 3rd degree in 4 cases to 4th in 17 cases. The 20 cases of successful
      fiberoptic intubation were divided into 7 patients with and 13 without
      tracheostomy. The mortality rate was 14.3% in patients with tracheostomy and
      30.8% in those without tracheostomy. When more than 4 intubation trials were
      needed, there was a significantly higher mortality rate. In neurologically
      handicapped patients with deformity or hypertonia of the oral, cervical, or
      airway structures, a bronchofiberoptic procedure may be recommended when there is
      difficulty with intubation.

PMID- 16296355
TI  - [Tracheomalacia in patients with severe motor and intellectual disabilities].
AB  - A total of 18 patients with severe motor and intellectual disabilities are
      reported, including 17 identified as having tracheomalacia (TM) by
      bronchofiberscopy and 1 suspected case. The clinical backgrounds, bronchoscopic
      findings, managements and outcomes of these patients were studied. The ages
      ranged from 2 to 41 years old (mean : 22.8 years). Fourteen patients had cerebral
      palsy and 4 had other neuromuscular diseases. More than 80% of the patients had
      flattening of the thoracic cage, scoliosis, and recurrent respiratory infections.
      Bronchofiberoptic videoscopy revealed a mean 73.6% narrowing of the trachea, and
      3 cases had 100% obstruction. The crescent type and a newly identified flat type
      of TM were observed, but there was no saber-sheath type. Attacks of cyanosis and
      transient or sudden respiratory difficulties were important symptoms for TM in 13
      cases. TM may cause sudden death in these patients. Tracheostomy may be
      recommended for severe cases with TM. An adjustable tracheostomy tube improved
      the narrowing of the trachea significantly in 6 cases. Bronchofiberoptic
      videoscopy is nessesary for accurate evaluation of TM and an adjustable
      tracheostomy tube may be useful for selected patients.

PMID- 16296356
TI  - [Dental enamel pitting in tuberous sclerosis complex].
AB  - We studied pitting of the dental enamel in cases of tuberous sclerosis complex
      (TSC), by staining defect sites. Many pits were found in the enamel of the TSC
      patients, especially on the labial surface of the incisors. Although the
      pathogenesis is unclear, pits of this type have been reported in TSC patients,
      but in the author's experience, have never been observed in cases of other
      diseases. On the basis of the results in this study and those previously
      published, we conclude that dental enamel pitting is a finding which suggests the
      diagnosis of TSC.

PMID- 16296357
TI  - [Complications of tracheostomy in a patient with severe motor and intellectual
      disabilities].
AB  - A patient with severe motor and intellectual disabilities, who had been admitted
      for a short stay, suffered cardiopulmonary arrest and was maintained on a
      ventilator after resuscitation. One month and 3 years after tracheostomy,
      arterial bleeding from the trachea occurred three times. Each time, the patient
      was successfully salvaged by arterial compression by hyperinflation of the
      endotracheal tube cuff and rapid blood transfusion. Long-term intubation caused
      stenosis and formation of a mucosal bridge in the trachea. After stenting failed
      to relieve the stenosis, laser ablation of the mucosal bridge was temporarily
      successful. Interruption of the brachiocephalic artery and partial resection of
      the sternal bone and insertion of an adjustable canula was successfully performed
      thereafter. This case suggests the necessity for both prophylaxis and adequate
      treatment of the various complications of tracheostomy.

PMID- 16296358
TI  - [An case report of a therapeutic vancomycin monitoring in an infant with shunt
      related purulent meningitis].

PMID- 16296359
TI  - [Recent evidences in the pharmacological mechanisms of the tramadol].
AB  - Tramadol [(1R, 2R) and (1S, 2S)-2-dimethyl-amino-methyl-1-(3-methoxyphenyl) 
      cyclohexanol hydrochloride] has been used clinically. It binds to micro-opioid
      receptors with lower affinity than morphine, which suggests that the
      antinociceptive action of tramadol may not be due to opioid receptor binding.
      Several lines of evidence have shown that tramadol inhibits the reuptake of
      monoamines, as do antidepressant drugs such as desipramine. Tramadol inhibits the
      reuptake of NE and serotonin. The mechanisms of action of tramadol have not been
      well understood. Recently, some evidences in the mechanisms of action of tramadol
      have been published. Tramadol inhibits the muscarinic receptor, serotonin
      receptor, and nicotinic acetylcholine receptor ion-channel, suggesting these
      receptors might be related to the mechanisms of action of tramadol. In this
      review, the mechanisms of action of tramadol were reviewed form these findings.
      Tramadol does not alter renal blood flow (RBF) in normal rats. This suggests that
      tramadol would be a safe analgesic maintaining RBF during the postoperative
      period. It would be necessary to study the effects of tramadol on orphan G
      ptotein coupled receptor which is related to the pain.

PMID- 16296360
TI  - [Augmentation of hypoxic pulmonary vasoconstriction in isolated rabbit lungs with
      phosphoenolpyruvate].
AB  - BACKGROUND: Phosphoenolpyruvate (PEP) is a glycolytic substrate which can be
      metabolized to pyruvate with concomitant formation of ATP. We examined the
      effects of PEP on hypoxic pulmonary vasoconstriction (HPV). METHODS: Isolated
      rabbit lungs (n = 6) were reperfused at a flow rate of 40 ml x kg(-1) body weight
      x min(-1) with a mixture of the physiological salt solution and autologous blood.
      They were ventilated with a mixture of 21% O2, 5% CO2, and balance N2. The HPV
      response was induced by reduction of inspired O2 concentration from 21 to 3% for
      5 min and was evaluated by an increase of the pulmonary arterial pressure (PAP)
      with inhalation of nitric oxide (NO) at concentration of 0, 10, 20 ppm in random
      order. Next, PEP with the final concentration of 10 mM was added to the
      reservoir. After 30-min equilibration, the above protocol of hypoxic stimulations
      was repeated. RESULTS: PEP did not alter the basal PAP, but augmented the HPV
      response. Without and with PEP, inhaled NO depressed the HPV response in a dose
      related manner and the half inhibition values (ED50) were 9.4 +/- 2.2, 14.9 +/-
      10.3 ppm (mean +/- SD), respectively. CONCLUSIONS: The combination of intravenous
      PEP and inhaled NO may improve PaO2 without increasing PAP in acute respiratory
      failure.

PMID- 16296361
TI  - [Comparison of propofol LCT and propofol MCT/LCT regarding the injection pain at
      different sites and the memory].
AB  - BACKGROUND: Incidence and intensity of pain on intravenous injection of propofol
      LCT were compared with those of propofol MCT/LCT. METHODS: Eighty adult patients
      scheduled to receive general anesthesia were divided into two groups, propofol
      LCT (Group L, AstraZeneca) and propofol MCT/LCT (Group M, Maruishi
      Pharmaceutical). The peripheral vein was inserted with an 18 gauge intravenous
      catheter at the dorsal hand, the wrist, or the anterior brachial region. Propofol
      2.0 mg x kg(-1) was injected at the speed of 5 mg x sec(-1). Noninvasive arterial
      blood pressure, heart rate, a BIS value and a degree of pain were measured. We
      used chi2 analysis and Wilcoxon t-test for statistical evaluation. RESULTS: There
      was a significantly larger incidence of injection pain in the Group L than the
      Group M (70% vs. 30%). The pain at the brachial region was significantly less as
      compared with the wrist or the dorsal hand in both groups. The ratio of patients
      having the memory of pain on the next day to those complaing the injection pain
      was 50% in the Group L and 36% in the Group M. There were no significant
      differences between the two groups in changes in BIS values and doses of propofol
      necessary for the loss of consciousness. CONCLUSIONS: The results suggest that
      propofol MCT/LCT elicits less pain on injection than propofol LCT. The injection
      pain is less at the brachial region than the wrist or the hand. Amnesia of pain
      may be obtained both with propofol MCT/ LCT and propofol LCT.

PMID- 16296362
TI  - [Perioperative management of patients with Brugada syndrome].
AB  - In 1992, Brugada et al. first reported eight cases of ventricular fibrillation,
      in which ST-segment abnormalities in leads V1 through V3 along with T-wave
      inversion, and complete or incomplete right bundle branch block were observed on
      the standard 12-leads ECG. Since then, this syndrome has been widely recognized
      as one of important diseases that can produce sudden death in middle aged healthy
      males. The ECG morphology of Brugada syndrome is believed to be caused by either
      an accentuation of the notch in the early phase of the action potential or loss
      of the action potential dome in the epicardium. Mechanisms of ventricular
      fibrillation in this syndrome are still unclear, but thought to be phase II re
      entry caused by dispersion of the action potentials. It has been shown that
      mutations of the human cardiac Na+ channel gene (SCN5A) underlie multiple cardiac
      diseases including Brugada syndrome. In fact, single amino acid substitution
      within the SCN5A coding region can evoke a cardiac rhythm behavior. In this
      review, we will focus on recent progress of basic and clinical research of
      Brugada syndrome and perioperative management of this syndrome.

PMID- 16296363
TI  - [Effects of clonidine and midazolam on postoperative shivering, nausea, and
      vomiting].
AB  - BACKGROUND: Postoperative shivering, nausea, and vomiting are common problems
      after general anesthesia. We compared the effects of clonidine and those of
      midazolam on postoperative shivering, nausea and vomiting in elderly patients.
      METHODS: We studied 40 elderly patients (age > 60 yr) undergoing elective surgery
      under general anesthesia combined with epidural anesthesia. Patients were
      allocated randomly to receive oral clonidine 3-4 microg x kg(-1) (clonidine
      group) or intramuscular midazolam 0.04-0.05 mg x kg(-1) (midazolam group).
      Anesthesia was maintained with sevoflurane in a nitrous oxide and oxygen mixture,
      and fentanyl as needed, combined with epidural anesthesia with mepivacaine.
      Shivering, nausea, and vomiting were recorded at recovery from anesthesia, 3 h
      after the transference to the ward, and the next morning. Shivering was graded by
      using a three-point rating scale, whereas nausea and vomiting were assessed by
      means of a four-point rating. RESULTS: The incidence of shivering was lower at
      recovery from anesthesia in the clonidine group (P < 0.05). Likewise, the
      incidence of nausea was lower at recovery from anesthesia in the clonidine group
      (P < 0.05). There were no differences in shivering and nausea at other recording
      points. One patient in each group had vomiting. CONCLUSIONS: Clonidine
      premedication is effective for preventing shivering and nausea after general
      anesthesia combined with epidural anesthesia.

PMID- 16296364
TI  - [Effect of amino acid solution on intraoperative core temperature the influence
      of anesthetics].
AB  - BACKGROUND: Propofol anesthesia has more thermogenic effect than isoflurane when
      combined with amino acid solutions. The purpose of this study is to compare the
      effects of intraoperative administration of amino acid solutions on
      intraoperative core temperature under propofol anesthesia with those under
      sevoflurane anesthesia. METHODS: Thirty patients scheduled for total hip
      arthroplasty were randomly allocated to undergo either propofol anesthesia or
      sevoflurane anesthesia. i.v. amino acid infusion started at anesthesia induction
      in all patients. The values of tympanic temperature were recorded after
      induction, during surgery and at extubation. RESULTS: Patients in the two groups
      were comparable with their characteristics and anesthetic managements. The
      temperatures under sevoflurane anesthesia were unchanged during study, whereas
      those under propofol anesthesia decreased significantly. CONCLUSIONS: Sevoflurane
      anesthesia has more preventive effect on intraoperative hypothermia than propofol
      anesthesia when combined with amino acid solutions.

PMID- 16296365
TI  - [Actigraphic assessment of the effects of hypnotics on the night before surgery
      in relation with the severity of surgery].
AB  - BACKGROUND: Hypnotics have been used to provide adequate sleep on the night
      before surgery, but these effects have rarely been investigated. We investigated
      whether the preoperative hypnotic effects are related with the severity of
      surgery with quantitative evaluation using actigraph. METHODS: Sleep time on the
      night before surgery was evaluated after the administration of brotizolam 0.25 mg
      in 40 patients awaiting surgery; 20 patients for cardiovascular surgeries (Group
      I) and 20 patients for general surgeries (Group II). Sleep and awake state were
      identified by wrist activity measured with a motion-logger actigraph. Sleep time
      was assessed in total period from 22:00 to 6:00 and its 4 subdivided 2-hour
      periods (22:00-24:00, 24:00-2:00, 2:00-4:00, 4:00-6:00). RESULTS: The total sleep
      time in Group II (448 +/- 22 min) was significantly longer than that in Group I
      (409 +/- 44 min). Group I showed a significant reduction in sleep time in the
      period of 4:00-6:00 compared with other periods, whereas Group II did not show
      any difference among 4 periods. Group I showed significant shorter sleep time in
      the period of 4:00-6:00 compared with Group II. CONCLUSIONS: An actigraphic
      assessment of sleep time has demonstrated the possible influence of the severity
      of surgery on the sleep time on the night before surgery.

PMID- 16296366
TI  - [Asystole during electroconvulsive therapy].
AB  - BACKGROUND: Asystole during electroconvulsive therapy (ECT) has been reported as
      an uncommon but fatal complication. But cardiac movement during electrical
      stimulation has not been well known. METHODS: The cardiac movements during
      electrical stimulation of fifty psychiatric patients treated by ECT under general
      anesthesia were observed utilizing thoracic echocardiography. Observations of 117
      times were performed. Rate pressure products (RPP) immediately before stimulation
      and during 10 minutes after stimulation were calculated. Asystole was defined as
      absence of heartbeat for over 2 seconds. RESULTS: Asystoles were observed 57
      times (48.7%). The heartbeat recovered immediately after stimulation in all
      asystole cases. RPP increased just after stimulation in all cases. Asystole cases
      had significantly greater variation of RPP than cases without aystole. (P =
      0.0082). CONCLUSIONS: Electrical stimulation by ECT activates parasympathetic
      nervous system and convulsion by the stimulation activates sympathetic nervous
      system. As asystole case had good reactive automatic nervous system, asystole
      might have been provoked by the stimulation with a greater increase in RPP after
      the stimulation.

PMID- 16296367
TI  - [Combined use of paravertebral block and general anesthesia for breast cancer
      surgery].
AB  - BACKGROUND: Thoracic paravertebral block (TPVB) is reportedly a useful
      alternative of general anesthesia (GA) for patients undergoing major breast
      surgery. To provide surgical anesthesia by TPVB alone, however, demands
      considerable patient's discomfort during neural block and during surgery. This
      study was undertaken to investigate if TPVB adds to patient satisfaction when
      combined with GA for breast cancer surgery. METHODS: In 26 women (ASA I * II)
      undergoing modified radical mastectomy with axillary dissection, TPVB was
      performed at T 1 level and 15 ml of 0.5% ropivacaine was injected prior to
      induction of general anesthesia. After surgery, VAS (visual analogue scale, 0-100
      mm) pain scores and postoperative medication were recorded. These data with TPVB
      were compared with those of 17 patients who had previously undergone similar
      surgical procedure without TPVB in our hospital. RESULTS: The VAS scores in
      patients with TPVB were 34 +/- 45 mm (mean +/- SD) on admission to the recovery
      room and 15 +/- 5 mm next morning. Frequency of postoperative administration of
      analgesics in patients with TPVB was significantly less than those without TPVB.
      CONCLUSIONS: Above findings suggest that combined use of TPVB and GA may be a
      preferable choice of anesthesia for patients undergoing major breast cancer
      surgery.

PMID- 16296369
TI  - [Anesthetic managements of premature triplets for PDA ligation through median
      sternatomy].
AB  - Extreme premature triplets were scheduled for PDA ligation through median
      sternatomy. Anesthesia was maintained with fentanyl, ketamine, pancuronium and
      sevoflurane or isoflurane with N2O, oxygen and air. During operation, steady
      ventilation with low oxygen concentration was maintained. Monitoring size and
      contraction of hearts in the face, 5% albumine solution could be administered
      safely for hypotension after PDA ligation. PDA ligation through median sternatomy
      might be a less invasive surgical procedure.

PMID- 16296368
TI  - [Effect of esmolol on cardiovascular responses induced by scopolamine
      butylbromide].
AB  - BACKGROUND: Scopolamine butylbromide (hyoscine-N-butylbromide, HB) is an
      anticholinergic drug used as a smooth muscle relaxant, and is used even in some
      surgical procedures during general anesthesia. HB also causes an increase in
      heart rate as a side effect. The authors evaluated the efficacy of esmolol on
      hemodynamic changes induced by HB in major abdominal surgery under inhalation
      anesthesia. METHODS: Seventeen patients for major abdominal surgery were randomly
      assigned to control group (C group, n = 9) or to esmolol group (E group, n = 8).
      Anesthesia was induced with propofol and was maintained with isoflurane-nitrous
      oxide inhalation and intermittent administration of fentanyl and vecuronium. At
      the time of bowel anastomosis, 20 mg of HB was administrated as an antispasmodic.
      In E group, esmolol 0.6 mg x kg(-1) was administered immediately after HB
      administration. RESULTS: There were no differences in the patient background
      between the two groups. At 1 to 10 minutes after HB administration, heart rate
      increased significantly compared with that at pre-administration in C group,
      while there was no significant change in heart rate in E group. Heart rate in E
      group was significantly lower than that in C group at 2 and 3 minutes after HB
      administration. Blood pressure was not significantly changed in both groups
      during the observation period. CONCLUSIONS: The simultaneous administration of HB
      and esmolol was useful for heart rate control after HB administration.

PMID- 16296370
TI  - [Anesthesia for argon plasma coagulation therapy through the tracheostomy site].
AB  - We experienced a case of argon plasma coagulation (APC) therapy for bronchial
      obstruction. A 54-year-old man was scheduled for APC therapy for bronchial
      obstruction using bronchoscope via a tracheostoma. The patient had received left
      upper lobectomy four years before and laryngectomy and tracheotomy two years
      before. Anesthesia was induced with droperidol 2.5 mg, and gradual administration
      of fentanyl (total 125 microg) and midazolam (total 1 mg). Surgery was completed
      in 15 minutes under spontaneous breathing of air. In APC therapy, we cannot
      administer oxygen for fear of argon-ignited intratracheal combustion. Using small
      doses of droperidol, fentanyl, and midazolam, we could successfully anesthetize a
      patient for APC therapy through the tracheostomy site under spontaneous
      respiration with air.

PMID- 16296371
TI  - [Anesthetic management for partial lobectomy in a postpneumonectomy patient].
AB  - We report a postpneumonectomy patient who underwent partial lobectomy. A 74-year
      old man was scheduled for right partial lobectomy because of metastatic lung
      cancer. He had undergone left pneumonectomy 19 months before because of lung
      cancer. Anesthesia was maintained with intravenous propofol and thoracic epidural
      block. During surgery, respiration was maintained with mechanical and
      intermittent manual ventilation. Percutaneous cardiopulmonary support and high
      frequency jet ventilation were at hand but were not needed. There was no
      intraoperative hypoxia and the postoperative course was uneventful.

PMID- 16296372
TI  - [The obstruction of a port catheter during the induction of anesthesia].
AB  - A 44-year-old woman receiving home hyperalimetation with an implanted port
      catheter, was scheduled to undergo resection of ovarian cyst and adhesiotomy. For
      the induction of anesthesia, fentanyl 0.05 mg, thiopental sodium 200 mg, saline 5
      ml and vecuronium 10 mg were given through the port catheter. Although she fell
      asleep, she kept breathing spontaneouly. It was not possible to give any further
      drugs through this port catheter, suggesting obstruction of the catheter. The
      endotracheal intubation was assisted with sevoflurane 5% and suxamethonium 80 mg
      chloride given through the peripheral vein. Five ml of saline used to flash out
      thiopental sodium before the administration of vecuronium blomide was not
      considered to be adequate. An experiment was conducted to investigate how much
      saline is necessary to wash out completely the drug given previously. The results
      suggest that more than 10 ml of saline should be given through the port catheter.
      Various types of central venous catheters are being used. Precise knowledge of
      each catheter is necessary to use this indispensable central vein route,
      especially at the crucial timing, such as the induction of anesthesia.

PMID- 16296373
TI  - [A case report of rapid inhalation induction with sevoflurane in a patient with
      porphyria].
AB  - We experienced anesthetic management for a patient with acute intermittent
      porphyria. A 52-year-old woman underwent a partial right mastectomy. She was
      anesthetized with continuous thoracic epidural blockade combined with general
      anesthesia using nitrous oxide, oxygen and sevoflurane. To avoid porphyric
      attack, we chose vital capacity breath technique for rapid induction. We could
      successfully manage the patient during the perioperative period without
      appearance of porphyric symptoms. We conclude that vital capacity breath
      technique for rapid induction may be suitable for use in patients with porphyria.

PMID- 16296374
TI  - [A case of complete atrioventricular block after induction of general
      anesthesia].
AB  - A 75-year-old man with a past history of bilateral thalamic hemorrhage was
      scheduled for cholecystectomy and cholelithotomy under general anesthesia.
      Although the preoperative ECG showed a complete right bundle branch block, the
      echocardiogram revealed no abnormality. Anesthesia was induced with thiopental
      and vecuronium, and maintained with sevoflurane in oxygen. Soon after changing to
      the left decubitus position for the insertion of an epidural catheter, ECG showed
      complete atrioventricular block, which did not respond to atropine. Adrenalin was
      transiently effective, but arrhythmia continued. After administration of
      dopamine, norepinephrine and isoproterenol, we inserted a temporary transvenous
      pacemaker catheter, and the hemodynamics became stable by ventricular pacing. The
      operation was postponed. Subsequent cardiologic examination showed no ischemia.
      The atrioventricular block disappeared 7 hours after the induction of general
      anesthesia. We should be very careful with the anesthetic management of a patient
      with a complete right bundle branch block.

PMID- 16296376
TI  - [Perioperative management of a neonate with a retroperitoneal giant teratoma who
      underwent its extirpation under general anesthesia: a case report].
AB  - We gave anesthesia to a neonate with a retroperitoneal giant teratoma who
      underwent its extirpation. Even if patients have a prenatal diagnosis of teratoma
      like this case, there are many patients, especially infants, with severe general
      condition. We report the difficulty for management during anesthesia because of
      severe respiratory acidosis due to pressure from diaphragmatic pleura by tumor,
      severe circulatory disorder due to massive bleeding during operation and severe
      hyperkalemia due to renal failure.

PMID- 16296375
TI  - [Prophylaxis of perioperative pulmonary thromboembolism in a patient with anti
      phospholipid antigen syndrome].
AB  - A 68-year-old woman with anti-phospholipid antigen syndrome (APS) was proposed to
      undergo partial pulmonary resection for lung cancer. She suffered from mild
      cerebellar ataxia. Exercised 201Tl myocardial scintigraphy was performed due to
      abnormal Q wave in preoperative electrocardiography and showed old myocardial
      infarction in inferior-to-posterior area without myocardial ischemia. Cardiac
      function was marginally decreased in cardiac echographic evaluation. Arterial
      thrombosis by APS might cause cerebellar ataxia and myocardial infarction. Low
      molecular weight heparin (LMWH) was continuously infused from 1 hour prior to
      arrival in an operation room. Elastic stockings (ES) were worn from the morning
      of the operation in combination with the use of intermittent pneumatic
      compression apparatus (IPC). Significant bleeding was not observed
      perioperatively. Hypothermia was avoided by forced-air-warming therapy. She was
      transferred to ICU after the end of the operation. She was returned to her ward
      without IPC on the first postoperative day. Warfarin was given with the beginning
      of ambulation on the second postoperative day to keep PT-INR about 2. On the
      third postoperative day LMWH was discontinued and ES were taken off. The
      postoperative course was uneventful.

PMID- 16296377
TI  - [Pneumothorax revealed by postoperative computed tomography].
AB  - We report a case of pneumothorax revealed by postoperative computed tomography. A
      39-year-old obese woman (height 153 cm, weight 70 kg) with fractures of the
      radius, ulna, clavicle, and femur in a traffic accident, was scheduled for
      osteosynthesis. Anesthesia was induced with thiopental and maintained with 50%
      nitrous oxide in oxygen and sevoflurane. The Spo2 decreased from 99% to 94%
      during the surgery. Bilateral chest sounds were symmetrical. The Spo2 increased
      to 100% after discontinuation of nitrous oxide. Pneumothorax was not evident on a
      postoperative chest X-ray, but computed tomography of the chest demonstrated
      right-sided pneumothorax. An ECG electrode had overlapped the fractured rib on
      the preoperative chest X-ray.

PMID- 16296378
TI  - [Ropivacaine-induced grand mal convulsion after obturator nerve block].
AB  - We describe a patient to whom ropivacaine 150 mg had been administered during
      obturator nerve blockade and developed grand mal convulsions because of
      inadvertent i.v. injection. Venous blood samples were taken 15, 32 and 52 min
      after the convulsion. The measured total plasma concentrations of ropivacaine
      were 4.5, 3.5 and 2.9 microg x ml(-1) respectively. The peak plasma concentration
      at the time of the inadvertent i.v. injection was estimated to be 6.6 microg x
      ml(-1). The patient recovered uneventfully.

PMID- 16296379
TI  - [Anesthetic management for awake laparoscopic surgery for ectopic pregnancy in a
      patient with heterotopic pregnancy].
AB  - A 26-year-old woman with heterotopic pregnancy in the 8th week of gestation was
      scheduled for surgery for ectopic pregnancy. To reduce the effect on the
      intrauterine pregnancy, awake laparoscopic surgery was performed under spinal
      anesthesia with pneumoperitoneum pressure of 6 mmHg. Bilateral shoulder pain
      occurred when pneumoperitoneum pressure was increased to 8 mmHg. The pain
      disappeared after the pneumoperitoneum pressure was decreased to 6 mmHg.
      Attention should be paid to shoulder pain due to physical and chemical
      stimulation of the diaphragm by pneumoperitoneum. Postoperative pregnancy and
      delivery were uneventful.

PMID- 16296380
TI  - [Protection against mismatched transfusion during operation double check system].
AB  - BACKGROUND: Three mistakes in recording blood types in the operation sheets
      occurred at the operating room of Iwamizawa Municipal General Hospital in 3
      months (June-August, 2004). METHODS: From these accidents, anesthesiologists and
      the staff improved the blood typing checking system to prevent mismatched
      transfusion during operation as follows; 1. The blood typing must be done at our
      out-patient's department, while the blood group compatibility test must be done
      at our inpatient's department. 2. We must describe the results of blood typing on
      the anesthesia application form using red colored pen. More than two medical
      staffs must confirm it. 3. Before anesthesia, the anesthesiologist and the nurse
      should confirm the blood type in loud voice. After that, the nurse must mention
      blood typing on white board using a red colored pen. 4. Just before transfusion,
      the anesthesiologist and the nurse should confirm the blood group typing of the
      patient, that of the preserved blood, and the number of the blood group's
      compatibility test in loud voice. RESULTS: From September, 2004 to March, 2005 no
      accident of blood typing mistake occurred in our hospital. CONCLUSIONS: Double
      check system of blood types in surgical patients would be useful in protection
      against mismatched transfusion during operation.

PMID- 16296381
TI  - [Unnatural deaths and medicolegal autopsy system--consented autopsy and its
      future].
AB  - We actively examine the causes of non-criminal unnatural deaths here at the
      Department of Legal Medicine in Kitasato University School of Medicine. We dealt
      with 3565 cases of unnatural deaths during the ten years from 1994 to 2003
      (postmortem examinations, 1741 cases; consented autopsies, 1824 cases; autopsy
      rate, 51.2%). CONTENTS: deaths by diseases, 2291 cases (64.3%); deaths from
      external causes or others, 1274 cases (35.7%). The autopsy rate of deaths by
      diseases is 60.7% and that of deaths from external causes or others is 34.0%.
      Cardiopulmonary arrest on arrival (CPAOA) accounts for about half of total cases
      (50.8%), that is 1811 cases. Especially, consented autopsies in cases of non
      criminal unnatural deaths performed under the permission (autopsy consent) of the
      bereaved family are highly significant, since they can contribute to society as
      greatly as judicial appraisal, and can also contribute to undergraduate and
      postgraduate medical education. Consented autopsy is a procedure that enhances
      people's recognition of legal medicine in the society and universities. We expect
      that other universities will establish their own methods of medicolegal
      activities in the future by referring to our Kitasato University system as a
      model.

PMID- 16296382
TI  - [ABO blood group typing in forensic autopsies].
AB  - In forensic science and medicine the ABO system has been a major focus, since the
      record of this blood system is a very prevalent one and A, B and O(H) antigens on
      erythrocytes are also associated with other cells and tissues throughout the body
      and are known to be considerably stable to the such violent conditions as heating
      or drying. However the determination of the ABO grouping from the body often
      encounters the difficulty due to haemolytic erythrocytes, and putrefaction,
      mummification or skeletonization of the body during post-mortem interval. In this
      presentation I review the merit and demerits of the ABO blood-grouping methods
      utilized in my division at the forensic autopsies according to the
      haemagglutination, absorption-elution and histochemical techniques and ABO
      genotyping method. It is important for ABO grouping to know the distribution of
      the ABO antigen in the body. I would like to emphasize that the species
      identification prior to ABO grouping is an important procedure because forensic
      materials such as from saliva, urine and seminal fluid might be contaminated with
      the fluid from animals, and DNA extracted from vertebrate species might be
      amplified with the primer for ABO genotyping and the amplified PCR products might
      be hybridized to those from human.

PMID- 16296383
TI  - [Bioterrorism].
AB  - Biological terrorism is intentionally to use infectious substances for developing
      diseases or death in animals or humans, leading to disaster and panic in our
      community. Bioterrorism-associated diseases are mostly rare or eradicated
      infectious diseases, and recently, we do not have experience to make a clinical
      and laboratory diagnosis. In particular, these infectious diseases have
      incubation periods from infection to development of the disease. The staff
      working at public health institutions, including legal medicine, must be involved
      in as a first responder when bioterrorism would happen. The preparedness in
      general against bioterrorism and the bioterrorism-related diseases, such as
      anthrax, smallpox, viral hemorrhagic fever, tularemia, and botulinum toxin,
      important for us are described. Both medical knowledge of bioterrorism and the
      preparedness with training under simulation should be required in advance.

PMID- 16296384
TI  - [Chemical weapons and chemical terrorism].
AB  - Chemical Weapons are kind of Weapons of Mass Destruction (WMD). They were used
      large quantities in WWI. Historically, large quantities usage like WWI was not
      recorded, but small usage has appeared now and then. Chemical weapons are so
      called "Nuclear weapon for poor countrys" because it's very easy to
      produce/possession being possible. They are categorized (1) Nerve Agents, (2)
      Blister Agents, (3) Cyanide (blood) Agents, (4) Pulmonary Agents, (5)
      Incapacitating Agents (6) Tear Agents from the viewpoint of human body
      interaction. In 1997 the Chemical Weapons Convention has taken effect. It
      prohibits chemical weapons development/production, and Organization for the
      Prohibition of Chemical Weapons (OPCW) verification regime contributes to the
      chemical weapons disposal. But possibility of possession/use of weapons of mass
      destruction by terrorist group represented in one by Matsumoto and Tokyo Subway
      Sarin Attack, So new chemical terrorism countermeasures are necessary.

PMID- 16296385
TI  - [Basic plan of Tokyo Medical Examiner's Office against NBC disasters by
      terrorism].

PMID- 16296386
TI  - [Preparedness for terrorist attack in the United States--the role of forensic
      pathologists and medical examiners].
AB  - Long distance airplanes hijacked by terrorists suddenly struck the World Trade
      Center in New York City on September 11, 2001. The city responded with efficient
      emergency service and there were a number of learning points for future planning.
      Early activation of the Disaster Mortuary Operation Response Team (DMORT)
      provided efficient family assistance by setting up a comprehensive Information
      Database Center and assisted the Medical Examiner in identifying the deceased.
      DMORT is a federally funded emergency service, made up of volunteer medical
      examiners and mortuary personnel, which responds to assist the local medical
      examiners in just such overwhelming emergency situations. We had been warned that
      Los Angeles was targeted as a probable site for similar attacks by terrorist
      groups. In response, Los Angeles has setup a far more advanced response system,
      the Coroner's Special Operation Response Team (SORT). SORT consists of over ten
      specialized units, one of which is the Weapons of Mass Destruction (WMD) Unit,
      staffed by qualified personnel, which provide continuing training, using standard
      procedures, drills and maintenance of many specialized protective equipment.
      Current urgent preparedness training includes the plans for maintaining
      government business continuity, safe keeping of electronic records, handling of
      multiple, widely spread fatalities through wrap, tag and hold program at multiple
      sites, using body bag, tag and hold procedure. Staff recruitment and training,
      development of equipment with the newly designed mobile facility for long range
      storage and field operation is an ongoing process in order to be able to respond
      effectively to any disaster. We still need expansion of training and equipment
      for handling cases of exposure to chemicals, biologic agents, radiation and
      nuclear energy. Plans in process are to have integration with DMORT and establish
      advance geographic information system, accomplished through the internet, and
      provide field reporting, commands and resource coordination in real time.

PMID- 16296387
TI  - [Possible influence of psychotropic drugs detected in blood when determining the
      cause of death in medicolegal autopsy cases in the Tokyo Medical Examiner's
      Office].
AB  - We reviewed the records of 118 medicolegal autopsy cases, in which psychotropic
      drugs were detected in blood, in the Tokyo Medical Examiner's Office in 1997, to
      explore how the drug levels were considered in determining the cause of death.
      Names and doses of the drugs were clear in 70 of 118 cases, and in most cases of
      the 70 cases, multiple drugs (up to 13 drugs) were prescribed to a person. It was
      also evident that 75 of the 118 cases had demonstrated psychosis for several
      months to 38 years prior to death. No information concerning prescriptions or
      history of psychosis could be obtained in the other cases. The causes of death in
      these 118 cases were as follows: deaths from specific diseases, 30 cases (25.4%);
      deaths from extrinsic factors excluding drug intoxication, 22 cases (18.6%);
      suicide related to drug intoxication, 31 cases (26.3%); deaths from extrinsic
      factors related to drug intoxication suggestive of suicide, but not confirmed, 19
      cases (16.1%); non-suicide, including probable drug intoxication, 13 cases
      (11.0%); and deaths from malignant syndrome, 3 cases (2.5%). There were cases
      diagnosed as death from specific diseases based on morphological findings, though
      drug concentrations in blood were at a toxic or even lethal level. In some cases,
      drug intoxication was suspected, but drug levels in their blood were at a
      therapeutic level and there were no identifiable morphological changes directly
      associated with deaths, resulting in a cause of death other than drug
      intoxication being indicated. Thus, drug levels detected in the cadaver's blood
      are not always useful for determining the cause of death. This might be due to
      poor information on interactions between drugs (including alcohol), pathological
      changes or genetic variability of drug metabolism and excretion, and so on. Thus,
      further studies of these aspects are needed in order to make information on drugs
      detected in the cadaver more useful for determination of cause of death.

PMID- 16296388
TI  - [Forensic odontology].

PMID- 16296389
TI  - [Natural death in adults: part 1. External examination].

PMID- 16296390
TI  - [Impact of the change in criteria for hospital discharge of patients with
      tuberculosis based on the duration of hospitalization].
AB  - OBJECTIVES: The criteria for discharge from TB ward was changed from sputum
      culture negative to smear negative since January 2003 and the duration of
      hospitalization and the applicability of each criteria were analyzed. METHODS:
      Cases hospitalized from Jan. to Dec. 2003 (Group I) were compared with those
      hospitalized from Jan. 2000 to Dec. 2002 (Group II). In group I, we investigated
      which criteria was applied for each case. RESULTS: Shifting criteria from culture
      negative to smear negative, the median duration of hospitalization was shortened
      from 83 to 70 days, in particular in 20s, 30s and 70s. No effect however were
      found in patients with initially high grade excreter of AFB or extensive cavitary
      lesions. Although 44% of patients were discharged according to smear conversion
      to negative, this criteria could not be applied in 17% due to some reasons.
      CONCLUSIONS: Conversion to culture negative has been conventionally used for
      discharge criteria in Japan considering not only contagiousness of the disease
      but to maintain patients adherence to treatment. After the introduction of new
      criteria to shorten the hospitalization periods, Japanese style DOTS after
      discharge would be more important to maintain patients adherence to treatment. We
      will continue to evaluate the treatment completion rate.

PMID- 16296391
TI  - [Current situation of contacts examination and chemoprophylaxis for persons
      exposed to multi-drug resistant tuberculosis in ordinance-designated cities in
      Japan].
AB  - PURPOSE: To evaluate the current situation of contacts examination and
      chemoprophylaxis for those who were exposed to multi-drug resistant tuberculosis
      (MDR-TB) in Japan. OBJECT AND METHOD: The questionnaire survey was conducted
      about the MDR-TB patients and their contacts examination enforced in the
      ordinance-designated cities in Japan from 1998 to 2002. RESULT: Nine cities out
      of total 13 ordinance-designated cities replied to the questionnaire (69.2%). The
      cases newly diagnosed as MDR-pulmonary tuberculosis were 189 cases from 1998 to
      2002. Out of 189 cases, 34 MDR pulmonary tuberculosis patients were the source of
      MDR-TB infection. Among 659 individuals who were exposed to 34 MDR-TB, 58 persons
      (8.8%) were diagnosed as the contacts who were infected with MDR-TB. Out of 58
      persons, 41 had chemoprophylaxis; 18 with isoniazid (INH), 3 with Ethionamide
      (TH), 2 with INH + Rifampin (RFP) + Ethambutol (EB), and each one with EB +
      Pyrazinamide (PZA) + TH, PZA + TH, PZA + Levofloxacin, PZA + EB. In 6 persons,
      INH was changed to other medicines, and 8 persons were treated with unknown
      prescription. Thirteen contacts developed MDR-TB, and out of them, 9 cases had
      several problems when they developed MDR-TB. Those problems were the delay in
      detection, infection from hospitalization refused cases, infection at the time of
      bacteriological relapse, and no use of chemoprophylaxis. CONCLUSION: MDR-TB
      bacilli produce the tuberculosis infection similarly as the sensitive tubercle
      bacilli, and it is necessary to re-examine the action plan of contacts
      examination including chemoprophylaxis.

PMID- 16296392
TI  - [Case of endometrial tuberculosis].
AB  - A 66-year-old woman was referred to our hospital because of lochiorrhea. Uterus
      MRI and ultrasonography showed hydrometra. Endometrium biopsy revealed
      epithelioid cell granuloma, and vaginal discharge and endometrium culture was
      positive for M. tuberculosis. She was diagnosed as endometrial tuberculosis.
      After treatment with INH, RFP, and EB for 9 months, she recovered.

PMID- 16296393
TI  - [Chemoprophylaxis for tuberculosis].
AB  - In Japan, a person who is 29 or younger, contacted a tuberculosis patient
      recently and judged to have received infection is the object of the
      chemoprophylaxis by the public expenditure. On the other hand, in ATS/CDC, they
      call chemoprophylaxis as the treatment of latent tuberculosis infection, and if
      there is a strong possibility that a person may appear tuberculosis, they start
      chemoprophylaxis, regardless of age. We usually prescribe isoniazid for latent
      tubercular infection. The period of prescription is at least 6 months, which is
      effective, but 9 months is more desirable. Recently, in the West, tuberculosis
      are frequent among patients who are administered Infliximab, anti-tumor necrosis
      factor-alpha. In Japan, after 6 months' evaluation period for Infliximab
      medication to rheumatoid arthritis, 11 out of 2,000 became tuberculosis (100,000
      to 550). As for the tuberculin reaction before Infliximab medication, 2 were un
      carrying out and 4 were negative. Moreover, even in positive examples, many of
      them were small redness. From this result, the Japanese Society for Tuberculosis
      and the Japan College of Rheumatology advised jointly. Those who are using
      immunosuppressant drugs and a doctor judged that they need chemoprophylaxis are
      supposed to the start medication if they are positive in tuberculin reaction, or
      there are some proof of tubercular infection on chest X-ray film, or there are
      high possibility of having received tubercular infection. By carrying out active
      chemoprophylaxis regardless of age, tuberculosis from high risk group is expected
      to decrease.

PMID- 16296394
TI  - [State of the art: sequelae of tuberculosis].
AB  - Sequela of tuberculosis (TB sequela) is defined as the state with various
      secondary complications after healing of TB, such as chronic respiratory failure
      (CRF), cor pulmonale or chronic pulmonary inflammation. Pathophysiology of TB
      sequelae is consisted of disturbed pulmonary function, CRF, sleep disorder and
      pulmonary hypertension. In addition, secondary pulmonary infection with mycosis
      or nontuberculous mycobacteriosis (NTM) is difficult to be controlled.

PMID- 16296396
TI  - Identification and quantification of glycerolipids in cotton fibers:
      reconciliation with metabolic pathway predictions from DNA databases.
AB  - The lipid profiles of cotton fiber cells were determined from total lipid
      extracts of elongating and maturing cotton fiber cells to see whether the
      membrane lipid composition changed during the phases of rapid cell elongation or
      secondary cell wall thickening. Total FA content was highest or increased during
      elongation and was lower or decreased thereafter, likely reflecting the assembly
      of the expanding cell membranes during elongation and the shift to membrane
      maintenance (and increase in secondary cell wall content) in maturing fibers.
      Analysis of lipid extracts by electrospray ionization and tandem MS (ESI-MS/MS)
      revealed that in elongating fiber cells (7-10 d post-anthesis), the polar lipids
      PC, PE, PI, PA, phosphatidylglycerol, monogalactosyldiacylglycerol,
      digalactosyldiacylglycerol, and phosphatidylglycerol-were most abundant. These
      same glycerolipids were found in similar proportions in maturing fiber cells (21
      dpa). Detailed molecular species profiles were determined by ESI-MS/MS for all
      glycerolipid classes, and ESI-MS/MS results were consistent with lipid profiles
      determined by HPLC and ELSD. The predominant molecular species of PC, PE, PI, and
      PA was 34:3 (16:0, 18:3), but 36:6 (18:3,18:3) also was prevalent. Total FA
      analysis of cotton lipids confirmed that indeed linolenic (18:3) and palmitic
      (16:0) acids were the most abundant FA in these cell types. Bioinformatics data
      were mined from cotton fiber expressed sequence tag databases in an attempt to
      reconcile expression of lipid metabolic enzymes with lipid metabolite data.
      Together, these data form a foundation for future studies of the functional
      contribution of lipid metabolism to the development of this unusual and
      economically important cell type.

PMID- 16296395
TI  - Furan fatty acids: occurrence, synthesis, and reactions. Are furan fatty acids
      responsible for the cardioprotective effects of a fish diet?
AB  - Furan FA (F-acids) are tri- or tetrasubstituted furan derivatives characterized
      by either a propyl or pentyl side chain in one of the alpha-positions; the other
      is substituted by a straight long-chain saturated acid with a carboxylic group at
      its end. F-acids are generated in large amounts in algae, but they are also
      produced by plants and microorganisms. Fish and other marine organisms as well as
      mammals consume F-acids in their food and incorporate them into phospholipids and
      cholesterol esters. F-acids are catabolized to dibasic urofuran acids, which are
      excreted in the urine. The biogenetic precursor of the most abundant F-acid, F6,
      is linoleic acid. Methyl groups in the beta-position are derived from
      adenosylmethionine. Owing to the different alkyl substituents, synthesis of F
      acids requires multistep reactions. F-acids react readily with peroxyl radicals
      to generate dioxoenes. The radical-scavenging ability of F-acids may contribute
      to the protective properties of fish and fish oil diets against mortality from
      heart disease.

PMID- 16296397
TI  - Dietary alpha-linolenic acid increases brain but not heart and liver
      docosahexaenoic acid levels.
AB  - Fish oil-enriched diets increase n-3 FA in tissue phospholipids; however, a
      similar effect by plant-derived n-3 FA is poorly defined. To address this
      question, we determined mass changes in phospholipid FA, individual phospholipid
      classes, and cholesterol in the liver, heart, and brain of rats fed diets
      enriched in flax oil (rich in 18:3n-3), fish oil (rich in 22:6n-3 and 20:5n-3),
      or safflower oil (rich in 18:2n-6) for 8 wk. In the heart and liver
      phospholipids, 22:6n-3 levels increased only in the fish oil group, although rats
      fed flax oil accumulated 20:5n-3 and 22:5n-3. However, in the brain, the flax and
      fish oil diets increased the phospholipid 22:6n-3 mass. In all tissues, these
      diets decreased the 20:4n-6 mass, although the effect was more marked in the fish
      oil than in the flax oil group. Although these data do not provide direct
      evidence for 18:3n-3 elongation and desaturation by the brain, they demonstrate
      that 18:3n-3-enriched diets reduced tissue 20:4n-6 levels and increased cellular
      n-3 levels in a tissue-dependent manner. We hypothesize, based on the lack of
      increased 22:6n-3 but increased 18:3n-3 in the liver and heart, that the flax oil
      diet increased circulating 18:3n-3, thereby presenting tissue with this EFA for
      further elongation and desaturation.

PMID- 16296398
TI  - Effects of aging and dietary n-3 fatty acids on rat brain phospholipids: focus on
      plasmalogens.
AB  - The aging brain undergoes modifications in the lipid composition of cell
      membranes and especially in plasmalogens. These phospholipids represent between
      one-half and two-thirds of the ethanolamine phospholipids in the brain. They are
      known to facilitate membrane fusion and act as endogenous antioxidants. During
      normal aging and in some pathological conditions, plasmalogen and DHA levels
      fall. In this context, we aimed to evaluate the influence of n-3 FA intake on
      plasmalogens in the brain during aging. Littermates from two generations of n-3
      deficient rats were fed an n-3-deficient diet or an equilibrated diet containing
      either alpha-linolenic acid alone (alpha-LNA) or with two doses of DHA (0.3 or
      0.6% w/w). After weaning, 9 mon of diet, or 21 mon of diet, plasmalogen levels
      were assessed, and the sn-2 substitutions of plasmenylethanolamines were analyzed
      in the cortex, striatum, and hippocampus. Our results showed that plasmalogen
      contents were not influenced by the diet. Plasmalogen levels were significantly
      decreased in aged rats compared with adults, whereas DHA levels increased in the
      hippocampus and remained stable in the cortex and striatum. DHA levels were
      significantly and similarly increased in total phospholipids and especially in
      plasmenylethanolamines after 9 mon of diet containing alpha-LNA alone or combined
      with DHA. This study showed that each structure sustained specific age-induced
      modifications. Dietary n-3 FA may not oppose the physiological decrease in brain
      plasmalogen levels during aging. Moreover, alpha-LNA appears to be equally as
      potent as preformed DHA at replacing DHA in the brain of our rat model.

PMID- 16296399
TI  - Docosahexaenoic acid supplementation in vegetarians effectively increases omega-3
      index: a randomized trial.
AB  - Low red blood cell (RBC) membrane content of EPA + DHA (hereafter called omega-3
      index) has recently been described as an indicator for increased risk of death
      from coronary heart disease. The relationship between plasma and RBC FA, focusing
      on omega-3 index, and the response to DHA supplementation were investigated in a
      double-blind, randomized, placebo-controlled, intervention study. Healthy
      vegetarians (87 f, 17 m) consumed daily a microalgae oil from Ulkenia sp. (0.94 g
      DHA/d) or olive oil (placebo) for 8 wk. DHA supplementation significantly
      increased DHA in RBC total lipids (7.9 vs. 4.4 wt%), in RBC PE (12.1 vs. 6.5
      wt%), in RBC PC (3.8 vs. 1.4 wt%), and in plasma phospholipids (PL) (7.4 vs. 2.8
      wt%), whereas EPA levels rose to a much lesser extent. Microalgae oil
      supplementation increased the omega-3 index from 4.8 to 8.4 wt%. After
      intervention, 69% of DHA-supplemented subjects (but no subject of the placebo
      group) reached an omega-3 index above the desirable value of 8 wt%. Omega-3 index
      and EPA + DHA levels in RBC PE, RBC PC, and plasma PL were closely correlated (r
      always > 0.9). We conclude that an 8-wk supplementation with 0.94 g DHA/d from
      microalgae oil achieves a beneficial omega-3 index of > or =8% in most subjects
      with low basal EPA + DHA status. RBC total FA analyses can be used instead of RBC
      lipid fraction analyses for assessing essential FA status, e.g., in clinical
      studies.

PMID- 16296400
TI  - Eicosapentaenoic acid, but not oleic acid, stimulates beta-oxidation in
      adipocytes.
AB  - The beneficial roles of dietary fish oil in lowering serum TAG levels in animals
      and humans have been attributed in part to the high content of two n-3
      polyunsaturated very long-chain FA, EPA, and DHA. Recent studies show that EPA
      induces mitochondrial beta-oxidation in hepatocytes, which might contribute to
      the systemic lipid-lowering effect. Whether EPA affects FA storage or oxidation
      in adipocytes is not clear. To investigate this possibility, 3T3-L1 adipocytes
      incubated with EPA (100 microM) for 24 h were assayed for beta-oxidation,
      carnitine palmitoyl transferase 1 (CPT-1) activity, protein, and mRNA expression
      of CPT-1. For comparison, cells treated with oleic acid, octanoic acid, and
      clofibrate, a synthetic ligand for peroxisome proliferator-activated receptor
      alpha were also analyzed. Mitochondria were isolated by differential
      centrifugation, and the mitochondrial membrane acyl chain composition was
      measured by GLC. EPA increased the oxidation of endogenous FA but did not inhibit
      lipogenesis. Oleic acid and clofibrate did not affect FA oxidation or
      lipogenesis, whereas octanoic acid suppressed the oxidation of endogenous FA and
      inhibited lipogenesis. Increased beta-oxidation by EPA was associated with
      increased CPT-1 activity but without changes in its mRNA and protein expression.
      EPA treatment increased the percentage of this FA in the mitochondrial membrane
      lipids. We suggest that EPA increased the activity of CPT-1 and beta-oxidation in
      adipocytes by altering the structure or dynamics of the mitochondrial membranes.

PMID- 16296401
TI  - Effect of abomasal infusions of geometric isomers of 10,12 conjugated linoleic
      acid on milk fat synthesis in dairy cows.
AB  - The trans-10,cis-12 isomer of conjugated linoleic acid (CLA) decreases TAG
      accumulation in 3T3-L1 adipocytes, reduces lipid accretion in growing animals,
      and inhibits milk fat synthesis in lactating mammals. However, there is evidence
      to suggest that other FA may also exert antilipogenic effects. In the current
      experiment, the effects of geometric isomers of 10,12 CLA on milk fat synthesis
      were examined using four Holstein-British Friesian cows in a 4 x 4 Latin Square
      experiment with 14-d periods. Treatments consisted of abomasal infusions of skim
      milk, or skim milk containing trans-10,cis-12 CLA (T1), trans-10,trans-12 CLA
      (T2), or a mixture of predominantly 10,12 isomers containing (g/l00 g) trans
      10,cis-12 (35.0), cis-10,trans-12 (23.2), trans-10,trans-12 (14.9), and cis
      10,cis-12 (5.1). CLA supplements were prepared from purified ethyl linoleate and
      infused as nonesterified FA. Infusions were conducted over a 4-d period with a 10
      d interval between treatments and targeted to deliver 4.5 g/d of 10,12 CLA
      isomers. Compared with the control, trans-10, trans-12 CLA had no effect (P>
      0.05) on milk fat yield, whereas treatments T1 and T3 depressed (P < 0.05) milk
      fat content (19.8 and 22.9%, respectively) and decreased milk fat output (20.8
      and 21.3%, respectively). Comparable reductions in milk fat synthesis to 4.14 and
      1.80 g trans-10,cis-12/d supplied by treatments T1 and T3 indicate that other
      10,12 geometric isomers of CLA have the potential to exert antilipogenic effects.
      The relative abundance of cis-10,trans-12 CLA in treatment T3 and the low
      transfer efficiency of this isomer into milk suggest that cis-10,trans-12 CLA was
      the active component..

PMID- 16296402
TI  - Isolation and characterization of some hydroxy fatty and phosphoric acid esters
      of 10-hydroxy-2-decenoic acid from the royal jelly of honeybees (Apis mellifera).
AB  - The present work characterizes novel FA in the royal jelly of honeybees (Apis
      mellifera). TLC analysis showed that the chloroform/methanol extract obtained
      from royal jelly consists mainly of FA. The FABMS spectrum of this extract gave
      several ion peaks due to compounds with higher M.W. than those of the FA so far
      reported. The methanol extract was found to contain unknown phospholipids. By
      means of reversed-phase HPLC with various solvent systems, 13 compounds were
      obtained in pure state. Their structures including absolute configurations were
      determined by chemical, NMR, and MS spectral analysis. Six compounds were
      identified as novel mono- or di-esters of 10-hydroxy-2E-decenoic acid in which
      the hydroxyl group was esterified by another FA unit, and one was hydroxy-2E
      decenoic acid 10-phosphate. In addition, we demonstrated that 9-hydroxy-2E
      decenoic acid exists as a mixture of optical isomers.

PMID- 16296403
TI  - Synthesis and characterization of a series of carbamate-linked cationic lipids
      for gene delivery.
AB  - A series of pH-sensitive lipids, la-h [(2,3-bis-alkylcarbamoyloxy-propyl)
      trialkylammonium halide] and 2a-d (1-di-methylamino-2,3-bis-alkylcarbamoyloxy
      propane), with carbamate linkages between the hydrocarbon chains and an ammonium
      or tertiary amine head, were synthesized for liposome-mediated gene delivery. The
      variable length of the carbon chains and the quaternary ammonium or neutral
      tertiary amine heads allowed us to identify the structure-function relationship
      showing how these factors would affect cationic lipids in gene delivery
      performance.

PMID- 16296405
TI  - A rapid method for the quantification of fatty acids in fats and oils with
      emphasis on trans fatty acids using Fourier Transform near infrared spectroscopy
      (FT-NIR).
AB  - A rapid method was developed for classifying and quantifying the FA composition
      of edible oils and fats using Fourier Transform near infrared spectroscopy (FT
      NIR). The FT-NIR spectra showed unique fingerprints for saturated FA, cis and
      trans monounsaturated FA, and all n-6 and n-3 PUFA within TAG to permit
      qualitative and quantitative comparisons of fats and oils. The quantitative
      models were based on incorporating accurate GC data of the different fats and
      oils and FT-NIR spectral information into the calibration model using chemometric
      analysis. FT-NIR classification models were developed based on chemometric
      analyses of 55 fats, oils, and fat/oil mixtures that were used in the
      identification of similar materials. This database was used to prepare three
      calibration models-one suitable for the analysis of common fats and oils with low
      levels of trans FA, and the other two for fats and oils with intermediate and
      high levels of trans FA. The FT-NIR method showed great potential to provide the
      complete FA composition of unknown fats and oils in minutes. Compared with the
      official GC method, the FT-NIR method analyzed fats and oils directly in their
      neat form and required no derivatization of the fats to volatile FAME, followed
      by time-consuming GC separations and analyses. The FT-NIR method also compared
      well with the official FTIR method using an attenuated total reflectance (ATR)
      cell; the latter provided only quantification of specific functional groups, such
      as the total trans FA content, whereas FT-NIR provided the complete FA profile.
      The FT-NIR method has the potential to be used for rapid screening and/or
      monitoring of fat products, trans FA determinations for regulatory labeling
      purposes, and detection of contaminants. The quantitative FT-NIR results for
      various edible oils and fats and their mixtures are presented based on the FT-NIR
      models developed.

PMID- 16296406
TI  - [Revised criteria for the early diagnosis of diabetic nephropathy].
AB  - The Diabetic Nephropathy Committee recommends the use of revised criteria for the
      early diagnosis of diabetic nephropathy in Japan. The new criteria are as
      follows: 1) Urinary albumin should be determined by immunoassay using a morning
      spot urine sample in diabetic patients without proteinuria or with dipstick
      positive(+ 1) proteinuria. 2) A urinary albumin-to-creatinine ratio ranging from
      30 to 299 mg/ gCr in 2 or more of 3 specimens may be diagnosed as
      microalbuminuria. 3) Two alternatives, i.e. the urinary albumin excretion rate of
      30-299 mg/24hr in 24hr urine collection or 20-199 microg/min in timed urine
      collection can be used to detect microalbuminuria. 4) Renal hypertrophy and
      elevated urinary type IV collagen may indicate the existence of diabetic renal
      disease. 5) Microalbuminuria originating in non-diabetic diseases should be
      excluded.

PMID- 16296407
TI  - [Guidebook of renal biopsy. VII. Handling and preparation of specimens].

PMID- 16296404
TI  - Antioxidant activity of various teas against free radicals and LDL oxidation.
AB  - Tea is a widely consumed beverage throughout the world. We assessed the
      antioxidant activity of six teas, including the aqueous extracts of green tea and
      oolong tea (Camellia sinensis), tochu (Eucommia ulmoides), Gymnema sylvestre,
      Japanese mugwort (Artemisia princeps), and barley (Hordeum vulgare), against 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radicals and LDL oxidation, and examined the
      association of LDL oxidizability with the plasma catechin levels in 10 healthy
      volunteers with a single dose of 5 g green tea powder. In vitro, the inhibitory
      effects of DPPH radicals and LDL oxidation were found to be strongest in the
      extract of green tea and weakest in that of barley. After the ingestion of green
      tea powder, the lag time increased from basal 52.2 +/- 4.1 to 60.3 +/- 4.2 min at
      1 h and 59.5 +/- 4.1 min at 2 h, and then returned to the baseline lag time (51.9
      +/- 1.4 at 4 h and 52.1 +/- 4.7 min at 6 h). Regarding the plasma catechin
      levels, epigallocatechingallate and epicatechingallate significantly increased
      from basal 3.7 +/- 1.3 and 0.8 +/- 0.8 ng/mL to 65.7 +/- 11.6 and 54.6 +/- 12.6
      ng/mL at 1 h, and 74.4 +/- 18.6 and 49.4 +/- 7.1 ng/mL at 2 h, respectively.
      Green tea therefore showed the strongest antioxidant activity among the six
      different teas, and the inhibitory effects of green tea on LDL oxidation depended
      on the plasma catechin levels.

PMID- 16296408
TI  - [Guidebook of renal biopsy. VIII. Kidney biopsy in children].

PMID- 16296409
TI  - [Treatment guidelines for the idiopathic nephrotic syndrome in children].

PMID- 16296410
TI  - [Estimation of glomerular filtration rate by inulin clearance: comparison with
      creatinine clearance].
AB  - Inulin clearance (Cin) is widely believed to be the gold standard of the
      glomerular filtration rate (GFR). However, in Japan, Cin has not been officially
      recognized by the Ministry of Health, Labour and Welfare of Japan for clinical
      use. Creatinine clearance (Ccr) has been used to estimate the renal function of
      patients, but there have been many studies in which Ccr estimates were GFR
      falsely high because the metabolism and tubular excretion of creatinine widely
      varied according to the pathophysiological state of the patient. In the present
      study, we determined Cin and Ccr simultaneously in 116 adult patients with renal
      diseases and diabetic mellitus. The clearance study was performed by the modified
      Wesson's method. The inulin preparation was FFI-1010 (Fuji Yakuhin Co. Ltd.).
      Inulin in serum and urine was determined by the newly devised enzymatic assay
      (Toyobo Co. Ltd.), which is specific for inulin. The mean Cin was 35.0 +/- 14.4
      ml/min/1.73 m2. The mean Ccr(the enzyme assay) was 63.6 +/- 24.1 ml/min/1.73 m2
      and that of the kinetic Jaffe assay was 55.3 +/- 19.3 ml/min/1.73 m2. Mean
      Ccr/Cin was 1.93 +/- 0.73, 1.69 +/- 0.62, respectively. This ratio was
      significantly different(p < 0.05) in the degree of reduction of Cin, with values
      of 2.07 +/- 0.82 (Cin < 40 ml/min/1.73 m2) and 1.64 +/- 0.32(40 < Cin < 80
      ml/min/1.73 m2), respectively. Only 8 patients were classified into the same
      degree of reduced renal function (the Guideline of Japanese Society of
      Nephrology). The findings of this study suggest that the GFR determined by Ccr
      could misjudge the renal function of patient and delay the administration of
      proper treatment of the patient. Introduction of Cin into the clinical field is
      necessary to avoid this delay.

PMID- 16296411
TI  - [Dialysis as bridge therapy for renal transplantation: single center experience,
      a comparison of hemodialysis and continuous ambulatory peritoneal dialysis].
AB  - BACKGROUND: Kidney transplantation is the most ideal treatment in renal
      replacement therapy for patients with end-stage renal disease. However, the
      prevalence of transplantation is extremely low and most patients with ESRD should
      continue dialysis for their whole life. Recently, high transposition rate of
      renal transplantation from peritoneal dialysis (PD) was reported, however, it was
      unclear whether a difference in dialytic modality can influence the outcome.
      Therefore, we evaluated the influence of dialytic modality on the rate of kidney
      transplantation and outcome in our single center. METHODS: Forty-two kidney
      transplants were carried among 1,573 dialysis patients from the years 1986 to
      2004 in our center. Transposition rates from two modalities (HD and PD) and graft
      survival were compared. The incidence of acute rejection episode, complications
      after receiving transplantations, and coexisting diseases were also evaluated
      between the two modalities prior to transplantation. RESULT: The number of
      patients who received HD was larger than PD (HD 77.1%, PD 22.9%, respectively).
      Forty-two patients undergoing dialytic therapy received a living-donor kidney
      transplantation. Overall graft survival was 92% at 5 years and 75% at 10 years.
      Among these cases, dialytic modality prior to transplantation was 57.1% in HD,
      and 42.9% in PD. The transfer rate from PD to transplantation was significantly
      (p = 0.0036) higher (4.7%) than that of HD (1.9%). The reason for the high
      transfer rate of PD patients might be cooperation with their family and the
      provision of relevant information by nephrologists during PD. There were no
      differences between the two modalities prior to transplantation in the graft
      survival rate, incidence of acute rejection, and complications before and after
      transplantation. CONCLUSION: Difference in pretransplant dialysis modality did
      not affect the outcomes, however, the transfer rate from PD was significantly
      higher than from HD. Accordingly, PD is useful compared to HD as bridge therapy
      for kidney transplantation from the high feasibility of living-donor kidney
      transplantation.

PMID- 16296412
TI  - [Blood ionized calcium fraction in various serum albumin levels surveyed in non
      dialysis patients].
AB  - Blood ionized calcium (iCa) fraction is affected by the serum albumin(Alb) level,
      even though this effect might not be appropriately estimated by the formulae
      proposed previously. To clarify a reasonable regimen for predicting iCa from
      serum total Ca (tCa), we investigated the relationship of blood iCa, tCa, and
      serum Alb levels through 124 samples from 116 non-dialysis patients requiring iCa
      measurement at the Nephrology Section of Toride Kyodo General Hospital. The
      patients comprised 61 males and 55 females with the mean age of 66.9 +/- 1.4
      years, including 9 cases of hypercalcemia, 110 of normocalcemia, and 5 of
      hypocalcemia based on their iCa levels. Their background diseases were 25 cases
      of chronic glomerulonephritis, 17 of nephrotic syndrome, 40 of diabetes mellitus,
      4 of collagen diseases, and 30 of others. Their mean serum Cr was 2.44 +/- 0.21
      mg/dl, and 77 patients showed elevated Cr levels. Four adjustment formulae: one
      derived from Payne's, two from the proposal of K/DOQI Clinical Practice
      Guidelines, and a theoretical one based on the previous in vitro experiments,
      were compared with the non-adjusted value (tCa itself) with respect to their
      suitability for estimating iCa. The correlation coefficient of tCa with iCa was
      higher than the values adjusted by the above four formulae. The difference of iCa
      from tCa divided by eight, which concisely predicted iCa based on the assumption
      that half the serum Ca is bound to protein, was less than 1/8th of the other
      adjusted Ca levels. Hence none of the adjusted Ca by the above formulae was
      superior to nonadjusted tCa from the point of estimating the iCa level. Moreover,
      the sensitivity for predicting hypocalcemia was the highest in tCa, even though
      its specificity was lower than the other adjusted values. In conclusion, no
      adjustment formula is required to predict ionized Ca from tCa, and to screen hypo
      or hypercalcemia.

PMID- 16296413
TI  - [Focal segmental glomerulosclerosis in a patient with polycythemia vera].
AB  - Herein we describe the case of a patient with focal segmental glomerulosclerosis
      (FSGS) following polycythemia vera (PV) on whom hemodialysis was started 7 years
      later. A 66-year-old woman who had been treated for PV with hydroxyurea and
      phlebotomy for three years was referred to our hospital because of nephrotic
      syndrome. Renal biopsy performed at her local hospital revealed FSGS. Although
      she had received prednisolone at an initial dose of 45 mg/day, no significant
      improvement of proteinuria was achieved. The dose of prednisolone was tapered
      because the second renal biopsy revealed sclerosing glomerulopathy. We considered
      that FSGS was associated with PV because renal hemodynamic alterations in PV
      could result in FSGS as in any other secondary FSGS and there was no proteinuria
      at the initial detection of PV. On January 29, 1999, she developed massive
      proteinuria (9.6 g/day) and the findings of the third renal biopsy worsened in
      comparison with that of the first renal biopsy. Thereafter, hydroxyurea or
      ranimustine was used in treating PV at an outpatient clinic. However severe
      thrombocytosis was difficult to control, and progressive renal dysfunction
      finally necessitated hemodialysis on January 18, 2005. In conclusion, physicians
      should be aware of the risk of progressive renal failure in patients with FSGS
      following PV, particularly in patients with persistent thrombocytosis.

PMID- 16296414
TI  - [Case of uremic platelet dysfunction].
AB  - The present case was a 59-year-old woman who underwent a right nephrectomy at 30
      years of age, and in whom renal dysfunction occurred at 51 years of age. In
      November 199X, when her creatinine level reached 7 mg/dl, renal replacement
      therapy was recommended. She refused this therapy and began her own diet therapy,
      which consisted of taking only supplement beverage, but no food. Afterwards she
      became unable to do daily work, and entered our hospital in July of the next
      year. On admission, her bleeding time was over 10 minutes, but coagulation
      function tests showed normal values. Platelet function tests showed that
      coagulation with the addition of ADP was mildly decreased and that coagulation
      with the addition of aggregation was severely decreased. These data and her
      bleeding tendency improved with hemodialysis. Therefore, a diagnosis of
      aggregation non-responsive uremic platelet dysfunction was made. On admission, we
      were not able to insert a catheter for hemodialysis because of her severe
      bleeding tendency. A platelet transfusion was made so that we could insert the
      catheter without severe bleeding. However, this hemostatic effect lapsed after
      about five to six hours. Six hours after insertion of the catheter, oozing from
      the orifice of the catheter was seen and a red blood transfusion was necessary.
      Three days after beginning hemodialysis, the bleeding tendency was no longer
      seen. Her platelet function and coagulation test results also improved. We can
      make two conclusions regarding this case. The first is when the physician's
      medical strategy cannot be carried out due to uremic platelet dysfunction, a
      platelet transfusion can temporarily eliminate the bleeding tendency. The second
      is that the pathophysiology of uremic platelet dysfunction involves suppression
      of the primary step of platelet aggregation with collagen. Experience with the
      present case revealed the appropriate therapeutic strategy for the
      pathophysiology of uremic platelet dysfunction.

PMID- 16296415
TI  - Weekend-trained injectionists.

PMID- 16296416
TI  - ADHD part two: accurate diagnosis and effective treatment.

PMID- 16296417
TI  - Diverse population presents health care challenges. Free CME training focuses on
      "cultural competence".

PMID- 16296418
TI  - "To whom much is given...".

PMID- 16296419
TI  - Fibromyalgia, why?

PMID- 16296421
TI  - Profile: Darrel Daugherty, DDS.

PMID- 16296420
TI  - Management of intractable chronic pelvic pain.

PMID- 16296422
TI  - The dental team: improving oral health together.

PMID- 16296423
TI  - I have had enough!
AB  - I apologize for making some of you nervous, and perhaps even resentful, but I
      HAVE HAD ENOUGH! I do not like the new unethical face of my profession, where
      incessant seeking of more money has replaced service to the public, honesty, and
      self-respect. Numerous areas of major ethical concern in dentistry are identified
      in this article. The ongoing, if not accelerating, degeneration of professional
      ethics in dentistry is clearly evident to even casual observers. Improvements in
      professional ethics are necessary to regain our self-respect and the respect of
      the people we serve. All of us need to improve, including practitioners,
      speakers, dental schools accomplishing research, manufacturers, editors, and
      evaluating groups. It is time to return to honesty and to dealing with our fellow
      men and women in the way we would want to be treated ourselves. I do not think it
      is too late.

PMID- 16296424
TI  - Xerostomia: a clinical approach.

PMID- 16296425
TI  - Analyses by photoreflectance spectroscopy and Vickers hardness of conventional
      and laser-assisted tooth bleaching.
AB  - PURPOSE: To evaluate the in vitro effects of two bleaching products developed to
      be used with halogen or argon laser lights. METHODS: 20 human embedded third
      molars were cut into four parts resulting in 75 useful specimens. The specimens
      were divided at random into five groups and submitted to the traditional power
      bleaching procedure for enamel. Group C was separated as a control group. Group
      37L was exposed to a 37% carbamide peroxide bleaching solution and exposed to 488
      nm argon laser radiation. The same solution was used in Group 37H but the
      bleaching was exposed to a halogen lamp-based unit. The 35% carbamide peroxide
      was used in Groups 35L and 35H. One was treated as in Group 37L and the other as
      in Group 37H. The samples were analyzed for Vickers hardness and also by
      photoreflectance. RESULTS: Group 37L presented more white spectra than Group 37H.
      However, Groups 35L and 35H showed similar results. Comparing both bleaching
      products, the 35% carbamide peroxide was more effective as a bleaching agent than
      the 37% formulation. No significant difference in Vickers hardness was noted
      between the two bleaching products.

PMID- 16296426
TI  - Effect of ozone on non-cavitated fissure carious lesions in permanent molars. A
      controlled prospective clinical study.
AB  - PURPOSE: To investigate, with a randomized controlled clinical study, the effect
      of ozone on non-cavitated initial occlusal fissure caries compared with untreated
      contra-lateral control lesions (split mouth) considering the patient's current
      caries risk. METHODS: Forty-one patients with 57 pairs of lesions were enrolled
      in the study (mean age 7.7 +/- 2.2 years; upper jaw n=29, lower jaw n=28).
      Gaseous ozone (HealOzone) was applied once for 40 seconds to the randomly
      assigned test molar of each pair without the use of remineralizing solutions.
      Lesion progression or reversal was monitored by the laser fluorescence system
      DIAGNOdent for up to 3 months and the deterioration or improvement compared
      between the ozone-treated lesions and the untreated control lesions (in pairs).
      This was done for the whole study population and a subgroup of patients with high
      current caries risk (lesion pairs n=26). RESULTS: After 3 months, explorative
      data analysis revealed that the ozone-treated lesions showed significantly more
      caries reversal or reduced caries progression than the untreated control lesions
      within the group of patients at high current caries risk (Wilcoxon-Test, P=
      0.035). There was no statistical significance examining the whole study
      population. From the data it can be concluded that ozone application
      significantly improved non-cavitated initial fissure caries in patients at high
      caries risk over a 3-month period.

PMID- 16296427
TI  - The dental pulp: inflammatory markers and vital bleaching.
AB  - PURPOSE: To evaluate the expression of specific neuropeptides associated with
      inflammation, substance-P (SP) and calcitonin gene-related peptide (CGRP), after
      night guard vital bleaching with 10% carbamide peroxide gel. METHODS: 10 patients
      with four caries free premolars scheduled for orthodontic extraction had these
      teeth bleached with 10% Opalescence as follows: tooth #28, no treatment
      (control); #5, 4 days of bleaching; #12, 2 weeks of bleaching; #21, 2 weeks of
      bleaching, followed by 2 weeks without treatment. All teeth in the four groups
      were extracted at the same time. Immediately after extraction the teeth were
      frozen at -197 degrees C in liquid nitrogen. The pulp samples were prepared for
      enzyme-linked immunoabsorbent assay (ELISA) to determine the concentrations of
      the SP, CGRP and total protein in the pulp tissue. RESULTS: The analysis of mean
      SP and mean CGRP/ng protein/ml resulted in no significant differences among the
      four groups. It was concluded that the study did not demonstrate an increase in
      the release of SP and/or CGRP during night guard vital bleaching of teeth with
      10% Opalescence.

PMID- 16296428
TI  - Influence of cavity configuration on the adhesion of two resin-based composites
      to pulpal floor dentin.
AB  - PURPOSE: To evaluate the effect of cavity configuration on microtensile bond
      strengths of two resin composites for core build-up to pulpal floor dentin.
      METHODS: Access cavity preparation and root canal filling with gutta percha were
      performed on extracted human molars. Following this, the gutta percha in the pulp
      chamber was completely removed to expose pulpal floor dentin. The cavity walls
      remained as a control group (Cavity). For another group, the cavity walls were
      removed to create a flat surface for bonding (Flat). For the Cavity group,
      Clearfil SE Bond was applied to the cavity according to the manufacturer's
      instructions, and either a light-cured resin composite (PH, Clearfil Photo Core)
      or a dual-cured resin composite (DC, Clearfil DC Core), was placed in the bonded
      cavity. Clearfil Photo Core was placed in three increments while bulk-filling was
      used for Clearfil DC Core. The application of the bonding system and the
      composites to the flat dentin surface was the same as that for cavity. Specimens
      were stored in water for 1 week, then sectioned vertically into 2 or 3 slabs (0.7
      mm thick) and trimmed for the microtensile bond strength (MTBS) test. The MTBSs
      were measured with a universal testing machine at a crosshead speed of 1.0
      mm/minute. RESULTS: The results (mean +/- SD, MPa, n=10) of PH/Cavity, PH/Flat
      and DC/Flat were 21.9 +/- 3.4, 28.9 +/- 4.0, and 27.6 +/- 6.1 respectively. The
      MTBS could not be determined in DC/Cavity because of debonding occurred during
      sample preparation.

PMID- 16296429
TI  - Comparative study of plaque removal efficacy of twin-motor sonic toothbrush with
      floating bristles and conventional powered toothbrushes in posterior teeth.
AB  - PURPOSE: To compare twin-motor sonic toothbrushes (TST) with conventional sonic
      (CST) and electric (CET) toothbrushes in terms of plaque removal efficacy.
      METHODS: A single-blind, triple-treatment cross-over study was conducted
      involving 36 participants. Each subject refrained from brushing for 24 hours;
      subsequently, subjects were screened for dental plaque in premolars and molars
      with the Rustogi Modified Navy Plaque Index. Plaque removal efficacy was
      determined according to percentage of plaque score reduction in a single
      toothbrushing under supervision for 2 minutes at the base of whole tooth surfaces
      and approximal areas. RESULTS: 35 subjects completed this study. No meaningful
      difference in pre-brushing plaque score was observed among the three
      toothbrushes. In molars, TST (48.3+/-3.3%) was higher in plaque removal efficacy
      relative to CST (40.4+/-2.4%, P= 0.0064) and CET (36.7+/-2.8%, P= 0.0001). This
      trend was obvious in approximal areas of the lingual aspect of the mandible;
      24.8% for TST versus 13.4% for CST (P= 0.0048) and 15.0% for CET (P= 0.0168). In
      premolars, TST displayed the greatest plaque removal efficacy, although the
      difference was significant exclusively for comparison with CET. These findings
      indicate that TST is more efficacious than CST and CET in terms of removal of
      plaque from molars, in particular, at approximal areas in the lingual aspect of
      the mandible, possibly due to new functions such as floating bristles and twin
      magnetic motors, which produce sonic vibration.

PMID- 16296430
TI  - Comparison of direct digital and conventional imaging with Ekta Speed Plus and
      INSIGHT films for the detection of approximal caries.
AB  - PURPOSE: To evaluate the accuracy of approximal caries detection comparing
      enhanced and unenhanced Sidexis CCD-based digital image with Ektaspeed Plus and
      INSIGHT films. METHODS: Fifty-two extracted premolars were imaged under identical
      standardized geometric and exposure conditions. Four observers, using five points
      confidence scale, rated 104 approximal surfaces for the presence or absence of
      carious lesions by means of four image modalities: (1) observer enhanced; (2)
      unenhanced Sidexis displays; (3) E speed films and (4) F speed film. Histologic
      sections served as validating criterion for the presence and depth of carious
      lesions. Diagnostic accuracy was measured as the area beneath the ROC curve.
      RESULTS: Mean ROC (receiver operating characteristic) curve areas for approximal
      surfaces were 0.865 (E speed), 0.856 (F speed), 0.816 (unenhanced Sidexis) and
      0.776 (observer enhanced). There were no significant differences between
      unenhanced digital Sidexis and films. Observer enhanced Sidexis images exhibited
      a statistically significant lower diagnostic accuracy than the film images for
      two of the observers.

PMID- 16296431
TI  - Confocal laser scanning microscopic observations of secondary caries inhibition
      around different types of luting cements.
AB  - PURPOSE: To analyze in vitro artificial secondary caries inhibition around
      conventional luting cements and resin cements using a confocal laser-scanning
      microscope (CLSM). METHODS: Box shape cavities (approximately 3 mm long, 4 mm
      wide, and 1.5 mm deep) were prepared in bovine root dentin. One of five cements:
      Elite Cement 100 (EL) zinc phosphate cement, HY-Bond Carbo Cement (CA)
      polycarboxylate cement, Fuji I (FI) glass-ionomer cement, Fuji Luting (FL) GIC
      based resin cement and Panavia F (PA) fluoride-releasing resin cement, was placed
      in the cavity. After polishing, the center of the cement surface was covered with
      an adhesive to preserve the original cement solubility. The specimens were stored
      in distilled water at 37 degrees C for 1 week, and stored in an artificial
      demineralizing solution for 3.5 days. Following this, each specimen was sectioned
      into two halves, trimmed, and polished. Thickness of inhibition zone, depth of
      outer lesion and cement solubility around each cement were determined by a CLSM.
      RESULTS: Inhibition zones were not seen in EL and CA, while they were found in
      FI, FL and PA. The depths of the outer lesions of CA and FI were significantly
      lower than those of EL, FL and PA (P< 0.05). The highest and the second-highest
      cement solubility were obtained in EL and CA, respectively. FI and FL indicated
      significantly lower cement solubility than EL and CA. PA tended to show the
      lowest cement solubility.

PMID- 16296432
TI  - Role of dentifrices on abrasion of enamel exposed to an acidic drink.
AB  - PURPOSE: To evaluate in vitro the abrasive potential of different dentifrices on
      enamel previously exposed to an acidic soft drink. METHODS: 150 bovine enamel
      slabs measuring 6 x 3 x 2 mm were grounded flat and polished. Surface roughness
      was measured to obtain Ra (microm) baseline values using a profilometer. The
      slabs' outer surface was covered with a tape except for a 3 x 4 mm window.
      According to a randomized complete block design, specimens were exposed to an
      acidic drink or distilled water (control) for 5 minutes, and then to artificial
      saliva for 1 minute. Next, the experimental units were submitted to 5,000
      brushing strokes using one of four dentifrices - regular (RE), baking soda (BS),
      tartar control (TC) or whitening (WT) - or distilled water as control (CO)
      (n=15). At the end of five repetitions of this erosive/abrasive cycle, the tape
      was removed and final readings of surface roughness were carried out. Roughness
      gain consisted of the subtraction of the baseline values from the post-treatment
      measurements. Also, the enamel wear due to erosive/abrasive challenges was
      profilometrically determined. RESULTS: ANOVA did not show significant interaction
      between enamel condition (eroded and sound) and dentifrice (P> 0.05) for both
      roughness gain and wear. No significant effect was found for enamel condition and
      dentifrice in the wear analysis. The exposure of enamel to the acidic drink
      provided higher roughness gain than did distilled water. Tukey's test evidenced
      that TC yielded significantly greater increase in surface roughness than did both
      CO and WT, whereas BS and RE induced an intermediate roughness gain.

PMID- 16296433
TI  - Shear bond strength of orthodontic brackets bonded with self-etching primers.
AB  - PURPOSE: To evaluate the effectiveness of two self-etching primers for bonding
      brackets in comparison with the conventional acid-etch technique. METHODS: The
      brackets were bonded to extracted human premolars using the resin orthodontic
      adhesive system, Transbond XT. This procedure was carried out in accordance with
      one of the following three protocols of enamel conditioning: (1) 37% phosphoric
      acid etching, (2) Transbond Plus Self Etching Primer (TSEP), and (3) Adper Prompt
      L-Pop (Adper PLP). Shear bond strength was measured with a universal test
      machine. The adhesive remnant on the tooth after debonding was quantified using
      image analysis equipment. Scanning electron microscopy (SEM) was used to observe
      the effects of conditioning of each product on the enamel. RESULTS: No
      significant differences were observed in bond strengths of the three groups
      evaluated (P> 0.05). Self-etching primers left significantly less adhesive on the
      tooth than the conventional acid-etch technique and, among them, Adper PLP left
      significantly less adhesive than TSEP (P< 0.017). SEM observations showed that
      the etching effect of self-etching primers approximated to the etching effect of
      phosphoric acid.

PMID- 16296434
TI  - Antibacterial activity of glass-ionomer cement containing antibiotics on caries
      lesion microorganisms.
AB  - PURPOSE: To assess the total viable bacteria in infected dentin after sealing
      with glass-ionomer cement containing 1% metronidazole, 1% ciprofloxacin and 1%
      cefaclor. METHODS: 40 children were selected, with ages ranging from 4-10 years,
      with primary teeth with active carious lesions without any pulpal involvement.
      The patients were divided randomly into two groups in accordance to the glass
      ionomer cement used to seal the carious lesions: Group 1 (control, n=20), sealing
      with conventional glass-ionomer cement; and Group 2 (test, n=20) sealing with
      glassionomer cement including antibiotics. The infected dentin was collected both
      before and 24 hours after the sealing of the cavities and, after inoculation in
      blood agar, all the plates were incubated in containers kept at 37 degrees C for
      5 days in an atmosphere of 85% N2, 10% CO2 and 5% H2, for subsequent counting of
      total viable bacteria. RESULTS: The results were analyzed using the Wilcoxon and
      Mann-Whitney tests. The glass-ionomer cement with 1% of metronidazole, 1% of
      ciprofloxacin and 1% of cefaclor showed a significantly greater reduction in
      microbiota in the infected dentin in comparison to the reduction with the
      conventional ionomer cement (P< 0.01), with a mean reduction of 98.65% of all
      viable bacteria. The infected dentin after sealing with glass-ionomer cement with
      antibiotics showed, using scanning electron microscopy, the presence of bacterial
      aggregates, intertubular dentin with exposure of collagen fibers, and dentin
      tubules.

PMID- 16296435
TI  - Cytotoxicity of a new toothpaste based on an ion exchange resin mixture.
AB  - PURPOSE: To evaluate the effects for cytotoxicity of two dentifrices: a
      toothpaste commercially available (Crest Extra-Whitening toothpaste) and a new
      experimental toothpaste based on a mixture of ion-exchange resins (named NMTD)
      that supplies calcium, fluoride, phosphate and zinc ions. METHODS: Cultures of
      mouse fibroblasts cells L929 were used in a MTT assay for in vitro cytotoxicity
      of the dentifrices. Cells were cultured in Eagle's minimal essential medium
      supplemented with 10% fetal bovine serum. Cultures were incubated at 37 degrees C
      in a humidified atmosphere of 5% CO2 and collected by tripsinization (0.05%
      trypsin/0.5mM EDTA). A 96-well microplate method was employed for the MTT
      colorimetric assay. Positive control consisted of 10 microl of phenol in 5 ml of
      6% media, a dose that produces zero percent cell survival. Negative control was
      prepared by adding 0.5 ml of HBSS to 4.5 ml of 6% media. The plates were
      incubated for 24 and 48 hours at 37 degrees C in a 5% CO2 atmosphere. RESULTS:
      Means and standard deviations of absorbance values for each group and percentage
      inhibitory dosage (%ID) for each test material were calculated. None of the
      dentifrices resulted in a percentage of inhibition higher than 50% and did not
      observe marked increases in cytotoxicity with time of incubation. The positive
      control gave almost zero percent cell survival, whereas the negative control gave
      a hundred percent cell survival. Analysis of the results indicated that test
      dentifrice dose had no significant effect towards the cell viability (P<0.05).

PMID- 16296436
TI  - Failure of anti-retraction valves and the procedure for between patient flushing:
      a rationale for chemical control of dental unit waterline contamination.
AB  - PURPOSE: To evaluate the efficacy of anti-retraction valves; and to compare
      between-patient flushing with water and with using a chemical treatment to
      control patient-to-patient contamination through dental unit waterlines (DUWL).
      METHODS: For the first aim, nine new antiretraction valves from three different
      manufacturers were utilized. Each valve was installed along the water line
      connecting the high-speed handpiece to the dental unit. The handpieces were made
      to run and stop in a container filled with a solution of about 7 log10/mL of
      Bacillus subtilis spores (used as a marker) and retraction of spores was
      measured. Subsequently, all nine valves were installed in dental units in use in
      private offices, and all tests repeated after 15, 30 and 60 working days. For the
      second aim, the efficacy of mechanical flushing (30 seconds for each instrument)
      was compared with that of mechanical flushing in combination with pressurized air
      and of a between-patient disinfecting procedure (2 minutes contact with TAED and
      persalt utilizing an "autosteril" system). Before each test (10 tests for each
      procedure), known concentrations of Pseudomonas aeruginosa (ATCC 27853)
      suspension (4 to 7 log10cfu/mL) was loaded in the DUWL and let sit for 20
      minutes. RESULTS: In the anti-retraction valve experiment, at baseline only one
      anti-retraction valve showed a failure in opposing fluid retraction. After 15
      days, three valves, after 30 days, six valves, and after 60 days, eight valves
      showed failure. In the flushing experiment, a highly significant linear
      correlation (r =.9178) was found between values before and after mechanical
      flushing. Post flush log10cfu/mL values showed the removal of about only 1
      log10cfu/mL of the microorganisms (only about 10% in absolute counts). On the
      other hand, no cfu/mL was detected in waterlines after the "autosteril"
      disinfecting cycles.

PMID- 16296437
TI  - All-ceramic partial coverage premolar restorations. Cavity preparation design,
      reliability and fracture resistance after fatigue.
AB  - PURPOSE: To investigate the effects of different cavity preparation designs on
      the reliability and fracture resistance of partial coverage restorations (PCR)
      which were luted adhesively to natural premolars after exposure to a mastication
      simulator. METHODS: 80 caries-free, extracted human maxillary premolars were
      randomly divided into two control groups (A, B) and three test groups (C-E)
      consisting of 16 specimens each. Group A served as a control group with no
      preparation. The specimens of Groups B to E were prepared as follows: Group B:
      MOD inlay, Group C: PCR (palatal), Group D: PCR (palatal and buccal), Group E:
      complete veneer. Using pressed ceramic IPS e.max Press (VP 1989), 64 all-ceramic
      restorations were fabricated and luted adhesively. The 80 specimens were
      subjected to 1.2 million mastication (F= 49 N) and 5500 thermal cycles at 5
      degrees C and 55 degrees C in a mastication simulator. Subsequently, all test
      specimens were loaded occlusally until fracture using a universal testing
      machine. The statistical analysis included the unpaired Wilcoxon rank sum test
      and box plots. RESULTS: All the specimens withstood the masticatory simulation.
      The following mean fracture strength values (N) (minimum/maximum) were recorded:
      Group A: 1446 (417/2404), Group B: 1351 (657/2096), Group C: 837 (346/1472),
      Group D: 963 (481/1691), Group E: 1361 (900/2211). The fracture strength values
      of Groups A, B and E were statistically significantly higher (P < 0.05) than
      those of Groups C and D. Inlays and complete veneers made of IPS e.max Press
      reached fracture strength values corresponding to those of natural premolars.

PMID- 16296438
TI  - Application of biologically-oriented dentin bonding principles to the use of
      endodontic irrigants.
AB  - PURPOSE: To compare the removal of smear layer and the structure of the hybrid
      layer formed after the use of EDTA or MTAD solutions when used as a final flush.
      METHODS: Single-rooted extracted premolars (n=18) were collected and treated for
      root canal therapy using NaOCl irrigation followed by a final rinse of 17% EDTA,
      Biopure MTAD, or saline (negative control). The roots were obturated with gutta
      percha and a hydrophilic HEMA-containing root canal sealer. The TEM specimens
      were impregnated with 50% silver nitrate to visualize sealing imperfections and
      nanoleakage. The structure of the coronal, middle and apical parts of root canal
      walls was examined using transmission electron microscopy. RESULTS: After NaOCl
      irrigation, a final rinse with BioPure MTAD or 17% EDTA completely removed the 2
      microm-thick smear layer on mechanically instrumented root canal walls. The
      BioPure MTAD hybrid layer was thicker than the 17% EDTA hybrid layer. Both the
      BioPure MTAD and EDTA caused a collapse of the dentin matrix structure which
      impeded sealer infiltration and the formation of high quality hybrid layer
      bonding. The hybrid layers created in smear layer-covered dentin exhibited less
      potential for nanoleakage than the MTAD or EDTA hybrid layers.

PMID- 16296439
TI  - Clinical effectiveness of two agents on the treatment of tooth cervical
      hypersensitivity.
AB  - PURPOSE: To investigate the desensitizing ability of a one-bottle bonding agent
      and a glutaraldehyde-based HEMA formulation on sensitive tooth cervical areas for
      a period up to 9 months. METHODS: The sample consisted of 40 patients with
      cervical hypersensitivity. Three sensitive teeth per patient were treated; one
      received One-Step (one-bottle bonding agent), the other Gluma Desensitizer
      (glutaraldehyde-based agent) and the third distilled water (control group). The
      hypersensitivity level was determined before, immediately after the desensitizing
      session, at 8 weeks, and 9 months post-treatment. Measurements of sensitivity
      were determined by the patient's response to tactile and air-blast stimuli. A
      verbal rating scale was used and scored as follows: 0, no discomfort; 1,
      discomfort but no severe pain; 2, severe pain during simulation; 3, severe pain
      after simulation. The results were subjected to statistical analysis by Kruskal
      Wallis test (a=0.05). RESULTS: Both treatment procedures resulted in reduction of
      hypersensitivity to both stimuli, for up to 9 months. No significant differences
      were recorded between One-Step and Gluma Desensitizer at immediate and 8-week
      examinations, whereas Gluma Desensitizer produced lower hypersensitivity than One
      Step at the 9-month assessment. In general, a lower level of reduction was found
      for the 9-month interval compared to the 8-week hypersensitivity score for both
      agents tested. A placebo effect was observed with water treatment, ranging from
      4.7 to 27.5% reduction of hypersensitivity.

PMID- 16296441
TI  - Morphologic changes in the microcirculation induced by chronic smoking habit: a
      videocapillaroscopic study on the human gingival mucosa.
AB  - PURPOSE: To analyze the gingival characteristics of microcirculation in vivo and
      to evaluate the effects of smoking by means of computerised videocapillaroscopic
      techniques. METHODS: 35 healthy non-smokers and 35 healthy smokers were examined.
      The characteristics of gingival microcirculation were examined using computerized
      videomicroscopic techniques. For each subject, visibility, course, tortuosity and
      any images characteristic of capillary loops, besides the possible presence of
      microhemorrhages, the average caliber of the capillary loops and the number of
      capillary loops visible per square millimeter were evaluated. The investigation
      was non-invasive and repeatable for each subject. RESULTS: The investigation of
      gingival mucosa revealed capillary loops with a course both parallel and
      perpendicular to the surface: close to marginal gingiva, the tops of the
      capillary loops often appeared as evenly distributed dots or commas; close to the
      papilla, microcirculation more frequently ran parallel to the surface, and its
      characteristics were similar to nail microcirculation. In smokers, it was
      possible to underline capillaries of a smaller caliber (P< 0.001) and a higher
      number of detectable capillaries (P< 0.001). An important correlation between the
      capillary tortuosity, close to the papilla, and the smoking habit (P< 0.001) was
      observed. This study has shown that the smoking habit represents a real risk
      factor for periodontal disease, which greatly affects microcirculation.

PMID- 16296440
TI  - The nature of the remaining dentin surface following application of Carisolv
      solution.
AB  - PURPOSE: To evaluate the effect of Carisolv solution on the topography and
      surface hardness of dentin. METHODS: Two separate studies were carried out.
      Atomic force microscopy (AFM) was employed to visualize dentin surface topography
      on slices of previously extracted non-carious and carious teeth following the
      passive application of Carisolv gel for 30- and 60-second periods. A Wallace
      hardness instrument was used to measure the dentin surface hardness following
      active caries removal with Carisolv gel and the specially designed instruments.
      Conventional caries removal with dental burs and non-carious dentin acted as
      controls for the latter study. RESULTS: AFM revealed that the passive application
      of Carisolv gel resulted in smoother surfaces than observed on carious and non
      carious dentin. There was a statistically significant difference between the mean
      hardness values for non-carious and Carisolv-treated dentin (P< 0.05). There was
      no statistically significant difference between the non-carious and bur-treated
      dentin nor the Carisolv and bur-treated dentin.

PMID- 16296442
TI  - Ultrafast EEG activities and their significance.
AB  - The true frequency range of the EEG is much broader than it has been assumed and
      taught for decades. The EEG apparatuses with inkwriting pens recording on paper
      are incapable of giving us trustworthy tracings beyond 80/sec. With the
      introduction of digital EEG machines, the exploration of the 60 to 1000 Hz range
      has already begun in the past few years (but, strangely enough, had been in use
      during the pioneer age when short photographic EEG recordings were made). The new
      wave of ultrafast recording began in the domain of somatosensory evoked
      potentials (SSEP). In the field of EEG (strictly speaking), research work started
      very recently. Ultrafast EEG activity promises new insights into the
      electrophysiological basis of epileptic phenomena. Activities from 150- to
      500/sec have been noted in recent studies (including personal work). Faster
      frequencies (500-1000/sec) are likely to play a major role in the
      electrophysiology of neurocognition and motor initiation. Such EEG-based
      neurocognitive studies will provide us with in-real-time data and thus outperform
      PET scanning and functional MRI. Even ultrafast EEG activity has its limitation,
      which appears to lie around 1000/sec. Faster frequencies (1000-3000 Hz)--recorded
      mainly with cathode ray oscillography--are probably incompatible with the
      shortest duration of true field potentials and might be nothing but "neuronal
      chatter."

PMID- 16296443
TI  - Paper recordings of ultrafast frequencies in experimental epilepsy.
AB  - Digital EEG technology has facilitated the recording of fast activity above 50
      Hz, but previous work carried out in this field is, commonly, no longer referred
      to in the literature. This paper presents a summary of our experience in
      experimental epilepsy when frequencies above 100 Hz were recorded. It was shown
      that conventional recordings (1-70 Hz) do not correlate with the onset of
      clinical seizures and can actually lead to misleading neurophysiologic
      conclusions. Ultrafast activity (100-1500 Hz), on the other hand, showed
      excellent correlation with clinical behavior and pointed to the low brainstem for
      the origin of nonfocal tonic-clonic seizures. In the animal analogue of absence
      seizures the cortex, including cingulate gyrus, thalamus, and cerebellum, showed
      greater involvement than other brain structures. Ultrafast activity has a very
      limited electrical field, and evoked responses remain restricted to the
      corresponding sensory pathways. Focal penicillin administration led not only to
      spike generation but also to associated ultrafast frequency bursts in that area.
      It appears likely that ultrafast burst activity may be a better marker for focal
      cortical epileptogenesis than spikes or sharp waves, which can be transmitted
      from a distance.

PMID- 16296444
TI  - Neural mechanisms of the ultrafast activities.
AB  - A brief review of previous studies is presented on ultra-fast activities > 300 Hz
      (high frequency oscillations, HFOs) overlying the cortical response in the
      somatosensory evoked potential (SEP) or magnetic field (SEF). The characteristics
      of somatosensory HFOs are described in terms of reproducibility and origin (area
      3b and 1) of the HFOs, changes during a wake-sleep cycle, effects of higher
      stimulus rate or tactile interference, etc. Also, several hypotheses on the
      neural mechanisms of the HFOs are introduced; the early HFO burst is probably
      generated from action potentials of thalamocortical fibers at the time when they
      arrive at the area 3b (and 1), since this component is resistant to higher
      stimulus rate > 10Hz or general anesthesia: by contrast, the late HFO burst is
      sensitive to higher stimulus rate, reflecting activities of a postsynaptic neural
      network in the somatosensory cortices, area 3b and 1. As to possible mechanisms
      of the late HFO burst genesis, an interneuron hypothesis, a fast inhibitory
      postsynaptic potential (IPSP) hypothesis of the pyramidal cell and a chattering
      cell hypothesis will be discussed on the basis of physiological and pathological
      features of the somatosensory HFOs.

PMID- 16296445
TI  - High-frequency oscillations in somatosensory system.
AB  - The recent revival of interest in high-frequency oscillation (HFO) is triggered
      by getting an opportunity to noninvasively monitor the timing of highly
      synchronized and rapidly repeating population spikes generated in the human
      somatosensory system. HFOs could be recorded from brainstem, cuneothalamic relay
      neurons, thalamus, thalamocortical radiation, thalamocortical terminals and
      cortex with deep brain or surface electrodes, or with magnetoencephalography.
      Here we briefly review the HFOs at each level of somatosensory pathways. HFOs
      recorded at brainstem might be produced by volume conduction from oscillations of
      the medial lemniscus. Thalamic HFOs at around 1000 Hz frequency would be
      generated within the somatosensory thalamus. Cortical HFOs would be generated by
      at least a few different mechanisms, thalamo-cortical projection terminals,
      interneurons and pyramidal cells of the primary sensory cortex. HFOs have been
      studied in several ways: their modulation by arousal changes, movements or drugs,
      their recovery function, effects of transcranial magnetic stimulation on them and
      also their changes in patients with various neurological diseases.

PMID- 16296446
TI  - High-frequency signals (> 400 hz): a new window in electrophysiological analysis
      of the somatosensory system.
AB  - High-frequency signals (HFSs) between 400-1500 Hz in Magnetoencephalography (MEG)
      and Electroencephalography (EEG) provide a new window in electrophysiological
      analysis of the somatosensory system in humans and in other animals. The HFS in
      the primary somatosensory (SI) cortex precedes the conventional N20. In the swine
      model, they appear to be due to spiking in thalamocortical axonal terminals and
      in the soma and dendrites of cortical neurons. These spiking activities seem to
      activate slower conductances in the pyramidal cells in layers II-III and V, which
      give rise to N20. The HFS monitoring may be useful for separately evaluating the
      electrophysiology of the subcortical and cortical components of the somatosensory
      pathway.

PMID- 16296447
TI  - 500-1000 Hz responses in the somatosensory system: approaching generators and
      function.
AB  - Spontaneous and stimulus-induced oscillatory EEG activities range over a wide
      scope of frequencies from 1 Hz to 1 kHz. In the ultrafast domain, trains of 5-10
      micropotentials are superimposed to primary thalamic and cortical components in
      somtosensory evoked potentials (SEP) as brief bursts of 1000 Hz and 600 Hz,
      respectively. Over the last years, hypotheses on generators and functions of this
      frequency-edge of population activity have been elaborated in numerous studies.
      Here, the relevant findings and ideas were surveyed from the body of literature.
      Special emphasis was paid to the anatomical and cellular origin of burst SEP,
      their assumed impact on somatosensory coding and perspectives for scientific as
      well as clinical applications.

PMID- 16296448
TI  - Phase clustering of high frequency EEG: MEG components.
AB  - The study of phase consistency of high frequency EEG/MEG components can reveal
      properties of neuronal networks that are informative about their excitability
      state. The clue is that these properties are easier to put in evidence when the
      response of the neuronal networks is evoked by an adequate stimulation paradigm.
      The latter may be considered a probe of neuronal excitability state capable of
      revealing hidden information contained in the phase structure of neuronal
      activities. In this context the high frequency band components appear to be the
      most reactive signals.

PMID- 16296449
TI  - Full-band EEG (fbEEG): a new standard for clinical electroencephalography.
AB  - A variety of neuroimaging techniques, such as functional magnetic resonance
      imaging (fMRI), positron emission tomography (PET) and magnetoencephalography
      (MEG), have been established during the last few decades, with progressive
      improvements continuously taking place in the underlying technologies. In
      contrast to this, the recording bandwidth of the routine clinical EEG (typically
      around 0.5-50 Hz) that was originally set by trivial technical limitations has
      remained practically unaltered for over half a decade. An increasing amount of
      evidence shows that salient EEG signals take place and can be recorded beyond the
      conventional clinical EEG bandwidth. These physiological and pathological EEG
      activities range from 0.01 Hz to several hundred Hz, and they have been
      demonstrated in recordings of spontaneous activity in the preterm human brain,
      and during epileptic seizures, sleep, as well as in various kinds of cognitive
      tasks and states in the adult brain. In the present paper, we will describe the
      practical aspects of recording the full physiological frequency band of the EEG
      (Full-band EEG; FbEEG), and we review the currently available data on the
      clinical applications of FbEEG. Recording the FbEEG is readily attained with
      commercially available direct-current (DC) coupled amplifiers if the recording
      setup includes electrodes providing a DC-stable electrode-skin interface. FbEEG
      does not have trade-offs that would favor any frequency band at the expense of
      another. We present several arguments showing that elimination of the lower
      (infraslow) or higher (ultrafast) bands of the EEG frequency spectrum in routine
      EEG has led, and will lead, to situations where salient and physiologically
      meaningful features of brain activity remain undetected or become seriously
      attenuated and distorted. With the currently available electrode, amplifier and
      data acquisition technology, it is to be expected that FbEEG will become the
      standard approach in both clinical and basic science.

PMID- 16296450
TI  - [At the XXXV anniversary of Romania's liberation from the Fascist domination].

PMID- 16296451
TI  - [The complications and morbid association of thyroiditis].

PMID- 16296452
TI  - [Etiology of neutropenias].

PMID- 16296453
TI  - [Acute episodes of air pollution with intoxication in the general population].

PMID- 16296454
TI  - [Nosocomial infections, yesterday and today. I].

PMID- 16296455
TI  - [The incidence of gastric ulcer and gastric cancer over an eight year period in
      the II-nd Medical Clinic of Iasi].

PMID- 16296456
TI  - [Early diagnosis of latent ischemic heart disease associated with asymptomatic
      hypothyroidism. Note I].

PMID- 16296457
TI  - [Considerations on pyloric ulcers].

PMID- 16296458
TI  - [Reversible and irreversible psychopathology in advanced age].

PMID- 16296459
TI  - [Clinical, pathologic and therapeutic aspects in thyroid cancer].

PMID- 16296460
TI  - [Rhino-cranio-cerebral wounds].

PMID- 16296461
TI  - [Biliary lithiasis after Reichel-Polya resection for duodenal ulcer].

PMID- 16296462
TI  - [Conservative surgery in renal coral-like calculosis].

PMID- 16296463
TI  - [Prolonged artificial respiration for the prevention of acute respiratory failure
      in patients with major thoraco-abdominal operations].

PMID- 16296464
TI  - [The presence of HBsAG in urine of patients with antigenemia].

PMID- 16296465
TI  - [Methemoglobinemia by phenacetin abuse].

PMID- 16296466
TI  - [Toxic risks in a polyester fiber plant].

PMID- 16296468
TI  - Human enteral infections caused by Yersinia enterocolitica.

PMID- 16296467
TI  - [Enteral infections with Yersinia enterocolitica].

PMID- 16296469
TI  - [The influence of the stress of examinations on some functional indices in
      student volunteers].

PMID- 16296470
TI  - [Benign retroperitoneal teratoma developing retrogastric in a 75 year-old man].

PMID- 16296471
TI  - [The characteristics of neuroendocrine regulation of the circulation in physical
      effort].

PMID- 16296472
TI  - [Histologic features of the ovary in hormone-dependent uterine neoplasias].

PMID- 16296474
TI  - [Aspects of the behavior of elderly subjects in ambulatory medical assistance].

PMID- 16296473
TI  - [Histochemical contributions to the metabolism of glycogen and
      mucopolysaccharides in experimental cerebral edema induced by hypoxia
      hypercapnia].

PMID- 16296475
TI  - [Synthetic prostacyclins, a new theoretical approach].

PMID- 16296476
TI  - [Some clinical and therapeutic aspects in extensive partial and total anodontia].

PMID- 16296477
TI  - [The study of neuromuscular imbalance in periodontal diseases].

PMID- 16296478
TI  - [Role of genetic factors in determining age and the sequence in the development
      of the permanent dentition].

PMID- 16296480
TI  - [Problems of the immunological diagnosis in rheumatic diseases].

PMID- 16296479
TI  - [Determination in vitro of the antibacterial action of Rifampicin (Sinerdol) as
      compared to other antibiotics].

PMID- 16296481
TI  - [Microbiological pollution of drugs and its practical implications].

PMID- 16296482
TI  - [Methodologic principles in exploration of the liver].

PMID- 16296483
TI  - [Investigations on chloramphenicol availability in ophthalmic lamellae].

PMID- 16296484
TI  - [The secretin-caerulein test in the diagnosis of chronic pancreatitis].

PMID- 16296485
TI  - [Bacitracin as a selective factor for the isolation of H. influenzae in primary
      culture from polymicrobial products].

PMID- 16296486
TI  - [Serologic diagnosis of respiratory viral diseases using a single serum sample,
      differentiation with 2-mercaptoethanol (2-ME) of the response in 19S and 7S
      antibodies].

PMID- 16296487
TI  - [Cosmetology in the treatment of acne].

PMID- 16296489
TI  - [Apudomas].

PMID- 16296488
TI  - [Siblings with partial albinism].

PMID- 16296490
TI  - [Nephrotoxicity to antibiotics].

PMID- 16296492
TI  - [Failure of cortisone treatment in some medium forms of viral hepatitis].

PMID- 16296491
TI  - [Primary cancer of the liver. Comments on etiology and diagnosis with reference
      to 56 cases].

PMID- 16296493
TI  - ["Legionnaires disease"].

PMID- 16296494
TI  - [Blood pressure in preschool children and family antecedents of atherosclerosis].

PMID- 16296495
TI  - [Study of the activity of some hepatic tissue enzymes as indicators of prognosis
      in chronic hepatitis].

PMID- 16296496
TI  - Spontaneous recovery in meningitis with TB bacilli in the cerebrospinal fluid.

PMID- 16296497
TI  - [Clinical and epidemiologic considerations regarding the incidence and evolution
      of and possible remission in late poststreptococcal articular rheumatic
      manifestations].

PMID- 16296498
TI  - [Experience at the I Surgical Clinic of Iasi in the treatment of rectal cancer].

PMID- 16296499
TI  - [Indications of the treatment with Enders elastic nail in fractures of the
      femur].

PMID- 16296500
TI  - [Comments on chronic sub-vater stenosis (D-3) due to mesenteric compression].

PMID- 16296501
TI  - [Reintervention after suture of perforated gastroduodenal ulcers].

PMID- 16296502
TI  - [The isolation of mucoproteins from the protein component of pulmonary
      surfactants].

PMID- 16296503
TI  - Transmitter release in ouabain treated Mg(2+)--paralysed neuromuscular junctions.

PMID- 16296504
TI  - [Study of wavy myocardial fibers. A morphologic reality in acute myocardial
      ischemia].

PMID- 16296505
TI  - [Influence of the epicutaneous test on lymphocytes in allergic contact eczema].

PMID- 16296506
TI  - [Left retro-aortic renal vein].

PMID- 16296507
TI  - [The fatigue factor in the determination of premature birth].

PMID- 16296508
TI  - [Primary and secondary chemoresistance in patients with pulmonary tuberculosis in
      the Iasi district during the 1975-1977 period].

PMID- 16296509
TI  - [Methods for the determination of phosphorus. 1. Determination of phosphorus in
      water by phenylhydrazine].

PMID- 16296510
TI  - Statistical and mathematical study on the characteristics of pulmonary x-ray
      images in influenza.

PMID- 16296512
TI  - [Fat-restricted diet in insulin-dependent diabetes mellitus].

PMID- 16296511
TI  - [Investigations on the HBsAg carrier state in a closed schoolchildren's
      community].

PMID- 16296513
TI  - [Clinical and therapeutical aspects in bronchopulmonary suppurations in the
      elderly].

PMID- 16296514
TI  - [Median cyst of the mandibula].

PMID- 16296515
TI  - [Study of the myotactical masseteric reflex in children].

PMID- 16296516
TI  - [Contributions to the quantitative study of lysergic alkaloid distribution in the
      sclerotia of Claviceps purpurea].

PMID- 16296518
TI  - [Medicamentous films].

PMID- 16296517
TI  - [Investigations on the interference of some new azopyrazolones in the metabolism
      of ethanol].

PMID- 16296519
TI  - [Capsulosyndesmoplasty of the knee].

PMID- 16296520
TI  - [Centering rotatory intertrochanterian osteotomy with joint control].

PMID- 16296521
TI  - [Indirect active transarticular stabilization].

PMID- 16296522
TI  - [Arthroplastic synovectomy of the knee].

PMID- 16296523
TI  - [Bacteriological and cytological examination in infections of the lower
      respiratory tract].

PMID- 16296524
TI  - [Comments with reference to two cases of Reye syndrome].

PMID- 16296525
TI  - [The origin of language according to E. B. Condillac].

PMID- 16296526
TI  - [Suspect death. Nosography and methodology].

PMID- 16296527
TI  - [Aspects of enzymatic induction (I)].

PMID- 16296528
TI  - [Epidemiologic aspects in genetic pneumonias: cystic fibrosis and alpha-1
      antitrypsin deficiency].

PMID- 16296530
TI  - Ectopic tachycardias with exit block.

PMID- 16296529
TI  - [Clinical and paraclinical aspects in Q fever].

PMID- 16296531
TI  - [Criteria of appraisal of the evolution and prognosis of chronic hepatitis].

PMID- 16296532
TI  - [Chronic lymphoblastic leukemia of the aged].

PMID- 16296533
TI  - [Experience in the treatment of burn shock].

PMID- 16296534
TI  - [Reconstruction of the anterior cruciate ligament of the knee by Lindemann's
      procedure].

PMID- 16296535
TI  - [Hypoglycemic Langerhans adenomas].

PMID- 16296536
TI  - [Influenza in Moldavia (Romania) in the winter of 1976].

PMID- 16296537
TI  - [Subclinical forms of viral hepatitis in the course of immunoglobulin
      prophylaxis].

PMID- 16296538
TI  - Hepatitis B antigen in saliva.

PMID- 16296539
TI  - [Study on the presence of methyl alcohol and some heavy metals in distilled
      beverages].

PMID- 16296540
TI  - [Bacteriologic study of primary chemoresistance in patients with pulmonary
      tuberculosis in the county of Iasi over a four year period (1971-1974)].

PMID- 16296541
TI  - [Analytical study of the therapeutic mud of Nicolina--Iasi].

PMID- 16296542
TI  - [Experimental investigations concerning the influence of nervous fatigue on
      cerebral metabolism].

PMID- 16296543
TI  - [Role of the reticular formation in cellular hyperplasia].

PMID- 16296544
TI  - [Investigations on the relationship between lactic acidosis and coagulopathy in
      experimental endotoxic shock].

PMID- 16296545
TI  - [The influence of insulin on hyperlactacidemia in the course of alloxan diabetes
      and experimental dysthyroidism].

PMID- 16296546
TI  - [Enzymatic changes in diabetes mellitus. Note I].

PMID- 16296548
TI  - [The treatment of dentin hyperaesthesia in periodontal diseases].

PMID- 16296547
TI  - [Enzymatic changes at the level of cerebral cortex experimentally induced by
      ischemia].

PMID- 16296549
TI  - [Problems of electrocardiographic diagnosis].

PMID- 16296550
TI  - [Investigations on a series of pentagonal heterocycles with nitrogen. Synthesis
      of some new benzimidazolyl-2-mercapto-acethydrazide hydrazones and testing of
      their cytostatic action on experimental tumours].

PMID- 16296551
TI  - [Proposals for the standardization of syphilis serodiagnosis (SSD), (Part II)].

PMID- 16296552
TI  - [Waaler-Rose reaction on plastic cup boards].

PMID- 16296553
TI  - [Bilateral ligature of the uterine arteries for controlling post-partum
      refractory hemorrhage].

PMID- 16296554
TI  - Advantages of local therapy by catheter in purulent pericarditis considerations
      of 4 cases.

PMID- 16296555
TI  - [Anterior spinal ischemia syndrome. Comments with reference to two clinical
      cases].

PMID- 16296556
TI  - [Articular hydatid cyst of the hip].

PMID- 16296557
TI  - Positive parenting as a protective resource for parentally bereaved children.
AB  - Positive parenting was examined as a protective resource against the adverse
      effects of negative life events on parentally bereaved children's mental health
      problems. The sample consisted of 313 recently bereaved children ages 8 to 16 and
      their current caregiver. Both the compensatory (direct effect independent of
      negative life events) and the stress-buffer (interactive effect with negative
      life events) protective resource models were examined and child gender was
      explored as a moderator of both models. Results revealed evidence for the
      compensatory protective resource model for both child and caregiver reports of
      mental health problems. No evidence of the stress-buffer model or child gender as
      a moderator was found. Implications for the understanding of children's responses
      to the death of a parent and the development and implementation of preventive
      interventions are discussed.

PMID- 16296558
TI  - Everybody's got something to hide except me and my patented monkey: patentability
      of cloned organisms.

PMID- 16296559
TI  - Physician assisted suicide: knowledge and views of fifth-year medical students in
      Germany.
AB  - Suicide and assisted suicide are not criminal acts in Germany. However,
      attempting suicide may create a legal duty for physicians to try to save a
      patient's life. This study presents data on medical students' legal knowledge and
      ethical views regarding physician assisted suicide (PAS). The majority of 85
      respondents held PAS to be illegal. More than a third of the students viewed PAS
      in certain situations to be ethically acceptable whereas a smaller proportion
      thought that it should be legal. Compared with German physicians the medical
      students taking part in this study were less opposed to PAS. The majority
      perceived the undergraduate training concerning ethical aspect of assisted death
      as deficient.

PMID- 16296560
TI  - Terrorism and resilience: adolescents' and teachers' responses to September 11,
      2001.
AB  - This study examined the impact of terrorism on adolescents, who may be resolving
      developmental issues regarding their vulnerability to death. Approximately 4
      months after the September 11th attacks, a survey was given to 973 Upper Midwest
      adolescents and teachers. Quantitative analyses indicated that adolescents
      (especially girls) were frightened and upset but also used many coping
      strategies. Qualitative analyses suggested that adolescents were angry as well as
      tired of hearing about the events. Teachers discussed the attack's historical
      significance, student safety, and a desire to resume "normalcy." Adolescence
      resilience was seen by the making of a coherent narrative of September 11th and
      by focusing on their daily living.

PMID- 16296561
TI  - And then the dog died.
AB  - Childhood grief and mourning of family and friends may have immediate and long
      lasting consequences including depression, anxiety, social withdrawal, behavioral
      disturbances, and school underachievement. Childhood pet bereavement is no less
      important, because the pet is often considered a member of the family by the
      child. However, society does not always acknowledge the significance of pet
      bereavement, which can result in unresolved grief. This article, a case analysis
      with literature review, addresses childhood pet bereavement in the context of
      multiple prior losses (K. R. Kaufman & N. D. Kaufman, 2005). This case mirrors
      both old and new findings in grief research and therapy: (a) beneficial response
      to emotional expression of grief in context of search for meaning; (b) beneficial
      response to cognitive approach toward grief with ability to prevent development
      of complicated grief even in the face of multiple losses; (c) beneficial effects
      associated with supportive family and with positive self-concept; (d) intensity
      of grief magnified by the child's degree of attachment to the pet, the suddenness
      of the pet's death, the multiple prior losses, and the role of the pet in the
      child's life; and (e) resiliency. This case further emphasizes the need for
      parents not to trivialize death of pets, to appreciate the role pets have in
      children's lives, and to assist the child in multiple approaches toward
      expression (be it verbal, written, or artistic). Finally, this case reinforces
      the ability of the child to assist in family bereavement and to serve as teacher.

PMID- 16296562
TI  - The daily life of complicated grief patients--what gets missed,what gets added?
AB  - Many patients with complicated grief suffer severe symptoms for several years
      after the loss, interfering with daily life. We sought to determine which
      elements of a patient's daily routine were likely to be missed or added. Sixty
      four patients completed a diary each evening for 2 weeks. The diary asked whether
      each of 13 daily life activities were done or missed on that day. Comparisons
      were made with 64 matched healthy control participants. Patients were
      significantly more likely than controls to miss contact with another person,
      breakfast, lunch, dinner, starting work, and going outside, and to add a nap and
      evening snack.

PMID- 16296563
TI  - Medicare advantage SNPs: a new opportunity for integrated care?
AB  - Medicare Advantage special needs plans (SNPs) are a new type of coordinated care
      plan established by the Medicare Prescription Drug, Improvement and Modernization
      Act. SNPs were created to encourage greater access to Medicare managed care for
      certain special needs populations: the institutionalized, persons dually eligible
      for Medicare and Medicaid, and the chronically ill. Some view SNPs as a new
      opportunity to integrate acute and long-term care services as well as Medicare
      and Medicaid financing. Others, however, question the degree to which full
      integration will become a widespread reality. This issue brief examines the SNP
      option and the promises and challenges it presents for better coordinated care.

PMID- 16296564
TI  - International standards for neurological classification of spinal cord injury.

PMID- 16296565
TI  - Recycling unused drugs.

PMID- 16296566
TI  - Solving big problems: a different perspective. Advice from four national experts
      on addressing the critical problems in the economy, homeland security, education
      and health care.

PMID- 16296567
TI  - Artificial insemination: its effect on paternity and inheritance rights.

PMID- 16296568
TI  - Change in and predictors of leisure activities among patients with rheumatoid
      arthritis: a prospective study.
AB  - OBJECTIVE: To describe factors associated with leisure activities, changes in
      leisure activities over time, and predictors of such changes among persons with
      rheumatoid arthritis (RA). METHODS: A prospective study was conducted of 80
      consecutive persons with RA, recruited while participating in a 3-week,
      rehabilitation day-care programme. The number of leisure activities was assessed
      through a structured interview. Sociodemographic variables, measures of disease
      activity [pain, patient's global assessment, C-reactive protein (CRP)],
      disability [Health Assessment Questionnaire (HAQ), Signals of Functional
      Impairment (SOFI), grip strength], quality of life at baseline, as well as
      disease activity [mean erythrocyte sedimentation rate (ESR)] and treatment
      (proportion of follow-up time on anti-rheumatic drugs during follow-up) were
      evaluated as possible predictors of change in leisure activities. RESULTS: Active
      leisure activities increased, while 'not obviously active or passive' leisure
      activities were unchanged during the follow-up period. The change in active
      leisure activities did not correlate with the predictors evaluated. CONCLUSION:
      The increase in active leisure activities was not predicted to a substantial
      degree by disease activity, disability, or medication. The results suggest that
      factors other than those evaluated influence changes in leisure activities.

PMID- 16296569
TI  - Low back pain: diagnosis, treatment, and prognosis.

PMID- 16296570
TI  - A systematic review of treatments for mild traumatic brain injury.
AB  - OBJECTIVES: To assess the effectiveness of interventions for mild traumatic brain
      injury (MTBI) in adults as found in the literature. RESEARCH DESIGN: Systematic
      review of the literature. METHODS: Six electronic databases and 18 journals
      within the brain injury field were manually searched between the years 1980-2003.
      References from articles were scanned for further literature. Studies that met
      broad inclusion criteria were subjected to a formal test of relevance. Those
      found to be relevant were qualitatively tested for their methodological
      soundness. RESULTS: One thousand and fifty-five studies were initially identified
      and 163 were assessed using the relevance tool, yielding 20 studies for review.
      Four categories of interventions were identified: Pharmacotherapy, Cognitive
      Rehabilitation, Patient Education and Other. The majority of studies were weak,
      however there is evidence to support the effectiveness of patient education
      interventions. CONCLUSIONS: There are few rigorous studies evaluating treatment
      of MTBI. Limitations of the current literature are presented.

PMID- 16296571
TI  - A randomized control trial to evaluate a paging system for people with traumatic
      brain injury.
AB  - Although memory problems following acquired brain damage are common, some people
      are able to compensate for these problems through external aids. It was recently
      demonstrated that a paging system could reduce the everyday memory and planning
      problems for people with non-progressive brain injury. The 143 patients who
      participated in the study comprised several diagnostic groups. This paper reports
      on the sub-group of people with TBI (n=63). This sub-group was part of the larger
      sample of 143 already published in the 2001 study. A randomized control cross
      over design randomly allocated people to group A (pager first) or group B
      (waiting list first). Each participant chose their own tasks for which they
      needed reminders. During a 2 week baseline, successful task achievement was
      documented. Group A achieved 47.14% of tasks and group B 47.88%. People in group
      A then received a pager for 7 weeks. During the last 2 weeks of this 7 week
      period, task achievement was documented again. Group A now achieved 71.80% of
      tasks and group B (on the waiting list) achieved 49.05% (no different from
      baseline). Group A then returned their pagers and group B received pagers. During
      the last 2 weeks of this stage participants were monitored once more. At this
      point, people in group A had dropped back slightly but were still statistically
      significantly better than during the baseline (67.23%). Group B, meanwhile, were
      now achieving 73.62% of tasks. This was statistically significantly better than
      baseline and significantly better than group A, now in the post-pager phase. It
      is concluded that this paging system significantly reduces the everyday memory
      and planning problems of people with TBI.

PMID- 16296572
TI  - Quality of life and antihypertensive effect with nebivolol and losartan.
AB  - BACKGROUND: Quality of life and antihypertensive effect, two important
      therapeutic goals, were determined with the third generation beta-blocker
      nebivolol and the angiotensin receptor blocker losartan are compared. METHODS: In
      a double-blind, randomized, parallel group study 314 patients with hypertension
      were treated for 12 weeks with 5 mg of nebivolol or 50 mg of losartan once daily.
      If after 6 weeks diastolic blood pressure (BP) was not normalized 12.5 mg of
      hydrochlorothiazide once daily was added. Effects of treatment were compared
      using analysis of variance. RESULTS: Both drugs decreased systolic BP similarly.
      The decrease in diastolic BP was greater (P < .0001) with nebivolol (-12 mm Hg
      after 6 and 12 weeks) than with losartan (-8 and -10 mm Hg after 6 and 12 weeks,
      respectively). Quality of life parameters did not differ between the two
      treatments. This was true after 6 and 12 weeks of treatment and results did not
      change when corrected for different effects on BP. Aspects of quality of life
      including questions on sexual function did not differ between the two treatments
      except for headache occurring less frequently (P < .05) in patients on nebivolol
      monotherapy at 6 weeks. CONCLUSIONS: At advocated doses nebivolol and losartan
      decrease systolic BP similarly, whereas the decrease in diastolic BP was slightly
      greater with nebivolol. Overall quality of life parameters did not differ between
      nebivolol and losartan. The effect on sexual function did not differ between the
      two treatments and less patients had headache with nebivolol than with losartan
      after 6 weeks of monotherapy.

PMID- 16296573
TI  - [Cochlear implants].

PMID- 16296574
TI  - Maintaining the cold chain for vaccines.
AB  - Cold chain for vaccines a is a system for storing and transporting vaccines at
      very low temperatures to maintain their effectiveness before use. Because
      vaccines are sensitive biological substances, their exposition to high
      temperatures directly affects the quality of vaccines and safety of immunization.
      The goal of this study was to assess the safety of cold chain for vaccines within
      the cold chain system in two services of Health Center Novi Sad. Cold Chain
      Monitors (CCM) and Freeze Watch (FW) indicators were used. A total of 155 (94.5%)
      Cold Chain Monitors (CCM) and 100 (95.2%) Freeze Watch (FW) indicators were
      analyzed. Only one CCM showed a breack in cold chain. A total of 3 CCMs indicated
      risk of vaccine wastage. A total of 9 CCMs were colorized without risk of vaccine
      wastage. FWs were positive in a high percentage in both services of Health Center
      Novi Sad. FWs were exposed to low temperatures during transport. Statistically
      significant differencies in the number of exposed CCMs to high temperatures and
      the number of exposed FWs to low temperatures were observed in these two
      services. A statistically significant difference in number of FWs exposed to low
      temperatures was observed in regard to the period of transport and the period of
      storage at the vaccination stations. The study shows high level of safety of the
      cold chain in two services of Health Center Novi Sad Cold Chain Monitor is a
      reliable indicator of the quality of cold chain for vaccines. Freeze Watch is a
      reliable indicator of the quality of cold chain during storage of vaccines, but
      not during their transport.

PMID- 16296576
TI  - [Reference values for the peak expiratory flow].
AB  - INTRODUCTION: Peak expiratory flow (PEF) is an important screening method for
      investigation and follow-up of the pulmonary function. Since reading the obtained
      PEF results requires reference values, the aim of this study was to establish
      normal values for PEF in our adolescent population. MATERIAL AND METHODS: The
      investigation included 1154 healthy teenagers aged from 15 to 19 years using a
      peak flow meter Harlow, Essex CM 2ED. Detailed explanations, purpose of
      investigation and function demonstrations were done prior to testing. Results
      were statistically analyzed. RESULTS: Obtained results showed an increase of PEF
      values with age and body height in both sexes. Elevation of PEF was more
      significant in boys; high correlation was found in regard to age and height in
      boys and moderate correlation in girls. DISCUSSION AND CONCLUSION: Regression
      equations for sex, age and height were made after measurements and data analysis.
      PEF values can be easily calculated knowing one's age and height.

PMID- 16296575
TI  - [Comorbidity of migraine and somatic diseases].
AB  - INTRODUCTION: A 5-year prospective follow-up study was performed at the Institute
      of Mental Health in Belgrade, and it included adult patients diagnosed with
      migraine. MATERIAL AND METHODS: A protocol for prospective follow-up of
      comorbiditiy of migraine and somatic diseases was designed, whereas data were
      analyzed using standard statistical methods. RESULTS: The study comprised 381
      patients, mean age 35.8 (range 19-60) years, 60 (15.8%) males and 321 (84.2%)
      females. The mean duration of migraine history before the first visit to the
      doctor was 7.7 (0-36) years. There was no concomitant disease in 50.5% of
      examinees. The most common concomitant diseases in the study population were:
      spondylosis (15.9%), head injury (12.9%), gynecological disorders (11.6% of
      female subgroup), hypotension (8.8%), hypertension (8.5%), allergy and asthma
      (5.8%), various cardiovascular diseases (4%) and epilepsy (3%). The incidence of
      the majority of diseases is in accordance with known epidemiological data for
      general population (except for head injury and epilepsy). In the subgroup of
      patients with comorbidity, almost 70% of patients reported more than one migraine
      attack per month, compared to 35% of patients without concomitant diseases, and
      about 60% of them had a higher intensity of headache in comparison with 35% of
      those without comorbidity. CONCLUSION: Present results indicate an increased
      severity of migraine attacks in patients with comorbidity. Therefore, it is
      necessary to assess how good management of comorbid diseases can alleviate the
      course and intensity of migraine headaches.

PMID- 16296577
TI  - [Tumor volume in advanced gastric cancer as a prognostic factor correlating with
      lymph node involvement].
AB  - INTRODUCTION: It has been established that measurement of tumor volume, rather
      than its diameter, is a better indicator of the depth of tumor invasion and lymph
      node involvement. The present study evaluates the significance of tumor volume as
      a prognostic factor in gastric cancer. MATERIAL AND METHODS: This prospective
      clinical trail included 87 patients with gastric cacncer admitted to Surgery
      Clinic "Dr. Dragisa Misovic" in Belgrade from 1998 to 2003. All patients were
      evaluated by standard diagnostic procedures, and after that underwent radical
      surgical treatment. Oncologic-surgical principles recommended by Japanese
      Research Society for Gastric Cancer were respected. Tumor volume was determined
      by measurement of specimens that had been obtained during surgery and by
      histopathological analysis. These criteria were analyzed and correlated with the
      lymph node status and clinicopathological factors. RESULTS: Single-factor
      analysis showed that lymph node metastases correlated with larger tumor diameter,
      larger tumor volume, depth of tumor invasion, diffuse and low-grade
      differentiation of the intestinal type of gastric carcinoma. Using a linear
      correlation coefficient, it was found that there was a highly significant
      correlation of tumor volume and number of metastatic nodes in groups between
      lymph nodes r = 0.567; p < 0.0001 in drainage group 1, r = 0.511; p < 0.0001 in
      drainage group II, r = 0.579; p < 0.0001 in drainage group III. Also, there was
      highly significant correlation with the total number of metastatic nodes (r =
      0.577; p < 0.0001) and significant correlation with the depth of tumor invasion
      and tumor diameter (p < 0.05). With 97% sensitivity and 88% specificity, "cut
      off" point was established by determining the tumor volume above which there were
      metastases into lymph nodes. In this study that volume was 2750 cmm. CONCLUSION:
      Tumor volume can be used as a valuable prognostic factor for advanced gastric
      cancer, and hopefully it will be calculated preoperatively by 3D-EUS volumetric
      analysis.

PMID- 16296578
TI  - [Constipation--a common problem in childhood].
AB  - INTRODUCTION: Constipation in children is defined as the infrequent and difficult
      passage of hard stool, not necessarily associated with in-frequent stools. All
      healthy newborns have their first stool within the first 24 to 48 hours after
      birth. Intestinal transit time increases with age, therapy decreasing the
      frequency of stooling. ANATOMY AND PHYSIOLOGY OF ANUS AND RECTUM: Acquisition of
      fecal continence requires: normal internal and external anal sphincters,
      puborectal muscle as well as intact sensory input from both the rectal vault and
      anal canal. ETIOLOGY AND DIFFERENTIAL DIAGNOSIS: During the first year of life,
      failure to have bowel movement every other day warrants evaluation. During
      infancy, constipation is usually due to dietary manipulations, malnutrition or
      some other functional abnormalities. Anatomic causes are found only in 5% of
      patients. DIAGNOSIS AND THERAPY: Diagnosis relies on history and physical
      examination. Digital rectal examination usually reveals a shorter anal canal with
      decreased sphincter tone. The rectal ampulla is dilated and filled with stool.
      Anorectal manometry is helpful in differentiating functional constipation from
      aganglionosis or other neurologic problems. Treatment varies depending on the
      underlying cause. Bowel retraining, aimed at establishing regular daily bowel
      movement, is of utmost importance in children. The response to treatment is
      usually dramatic. CONCLUSION: Constipation in children causes anxiety in the
      family and successful treatment requires persistent reassurance and repeted
      reevaluation.

PMID- 16296579
TI  - [Osteoprotegerin--a neutralizing receptor, protector of bones and a potential
      antiresorptive agent].
AB  - INTRODUCTION: The receptor activator of NF-B ligand (RANKL), expressed on the
      surface of osteoblasts and stromal cells in the bone marrow, plays an essential
      role in the formation and differentiation of osteoclasts and bone resorption.
      RANKL binds to its functional receptor, receptor activator of NF-B (RANK),
      expressed as a transmembrane heterotrimer on the surface of hematopoietic
      osteoclasts progenitors and mature osteoclasts. RANKL-RANK interaction is
      inhibited by soluble receptor-osteoprotegerin. OSTEOPROTEGERIN: Osteoprotegerin
      (OPG), a member of the tumor necrosis factor receptor superfamily, acts as a
      natural decoy receptor that blocks the interaction between RANKL and RANK. The
      balance between RANKL and osteoprotegerin is of major importance in bone
      homeostasis. Osteoprotegerin inhibits differentiation and formation of
      osteoclasts and induces apoptosis of osteoclasts. OPG knock-out mice develop
      severe osteoporosis. In contrast, overexpression of OPG in transgenic mice causes
      osteopetrosis. OSTEOPROTEGERIN AS A THERAPEUTIC AGENT: Antiresorptive activity of
      osteoprotegerin is proved in numerous experimental models. Osteoprotective effect
      of osteoprotegerin has recently been proved in postmenopausal women with
      osteoporosis as well as in patients with multiple myeloma and osteolytic
      metastases of breast cancer. CONCLUSION: Osteoprotegerin is a potent
      antiosteoclast agent that may prove useful in the treatment of bone disorders
      with net bone loss, such as postmenopausal osteoporosis and cancer metastases.

PMID- 16296580
TI  - [Thrombophilia and thrombosis].
AB  - INTRODUCTION: Generally speaking, thrombophilia includes all congenital and
      acquired conditions associated with increased susceptibility to thrombosis. An
      impaired balance between stimulating and inhibitory components of the hemostasis
      system may result in thrombosis or hemorrhage (extreme disorders), while
      moderately impaired hemostasis induces thrombophilia. THROMBOPHILIA,
      PRETHROMBOTIC STATE AND THROMBOSIS: A prethrombotic state is a condition of
      stimulated hemostasis system with tolerable intensity. When the activation level
      exceeds the capacity of inhibitory components, prethrombotic state advances to
      thrombosis. CLASSIFICATION OF THROMBOPHILIA: Thrombophilia is classified as
      primary or hereditary and secondary or acquired. Hereditary or congenital
      thrombophilia is a condition of congenital mutation of one or more antithrombotic
      components. Acquired or secondary thrombophilia accompanies a variety of
      pathologic conditions and diseases. LABORATORY DIAGNOSIS OF THROMBOPHILIA:
      Specific laboratory tests for congenital thrombophilia include assessment of the
      antigen component related to the activity of AT III, protein C, and protein S,
      evaluation of the resistance to the activated C protein, assessment of t-Pa and
      PAl-1 activity, as well as tests for hyperhomocysteinemia and prothrombin 20210
      mutation. MANAGEMENT OF THROMBOPHILIA: Treatment of patients with congenital AT
      III deficiency includes intravenous heparin and AT III concentrate (dosage 50 U/
      kgbw). Patients with heterozygous protein C and S deficiency are treated by
      intravenous heparin and oral anticoagulant therapy. Regarding arterial thrombosis
      due to confirmed congenital hyperhomocysteinemia, it is treated the same as
      venous thrombosis.

PMID- 16296581
TI  - Preterm and premature rupture of membranes in pregnancies after in vitro
      fertilization.
AB  - Women conceiving by assisted reproduction are at higher risk for preterm and
      premature rupture of membranes. The aim of our study was to estimate and compare
      incidence of preterm premature rupture of membranes in singleton pregnancies of
      women who conceived by intrauterine insemination and in vitro fertilization, from
      1999 to 2003. We investigated 87 women from the intrauterine insemination, and
      102 from the in vitro fertilization program. There were no statistically
      significant differences in regard to preterm and premature rupture of membranes:
      p > 0.75 in two groups. The incidence of premature rupture of membranes was 2.30%
      (after intrauterine insemination) and 2.94% (after in vitro fertilization). There
      was no statistically significant differences in regard to preterm and premature
      rupture of membranes in women who conceived by insemination and in vitro
      fertilization. Estimated incidence of preterm and premature rupture of membranes
      was similar to the literature data and also similar to incidence after natural
      conception.

PMID- 16296582
TI  - [Common errors in diagnosis and management of urinary tract infections-
      microbiological aspects].
AB  - INTRODUCTION: Urinary tract infections (UTI) are among the most common infectious
      diseases affecting all age groups, from infants to the elderly. The majority of
      these infections occur in otherwise healthy individuals who present with symptoms
      of acute uncomplicated bacterial cystitis or pyelonephritis. Certain patient
      populations with complicated conditions are at increased risk for acquiring
      infection or failing therapy. Forty to 50% of adult women have a history of at
      least one urinary tract infection. DIAGNOSIS AND CLASSIFICATION OF UTI: Although
      there are general guidelines concerning diagnosis and classification of urinary
      tract infections, there are wide variations in clinical practice. There are both
      errors which are frequently committed and mysteries that are still unsolved.
      Active management is important because under some circumstances urinary tract
      infections may cause permanent renal scarring. Imaging procedures are a
      cornerstone for critical evaluation of urinary tract infections, but avoidance of
      investigative routines will allow a marked saving in terms of costs and in terms
      of unnecessary radation and psychological stress to the patient.

PMID- 16296583
TI  - [Splenic capping in the treatment of severe spleen injuries].
AB  - INTRODUCTION: Permanent and lifelong threat of developing fatal sepsis and other
      severe infections in splenectomized patients is an important reason for promoting
      splenic preservation. MATERIAL AND METHODS: Experimental preservation of severe
      spleen injuries (grade IV), with splenic-capping, was performed in 30 dogs,
      operated using Ketalar anesthesia. Spleen preservation and concomitant treatment
      of excessive hemorrhage were achieved by highly controlled "conic" compression of
      injuried spleen parenchyma, additional hemostatic Z-sutures and fibrin tissue
      adhesion. RESULTS: Satisfactory hemostasis and complete preservation of the
      spleen parenchyma damage were achieved in 20% by splenic capping splenorraphy,
      alone. Additional placement of hemostatic sutures was necessary in 30%, and
      concomitant application of serum thymic factor (STF) FTA (along with sutures) in
      50% of patients. The above mentioned techniques were very effective in achieving
      hemostasis (100%), with no mortality and low rate of postoperative complications-
      6.7% (1 intrasplenic abscess and 1 adhesive ileus). CONCLUSION: Excellent results
      and efficacy, splenic capping-splenorraphy is the method of choice in the
      treatment of severe and multiple transcapsular spleen injuries with involvement
      of segmental vessels.

PMID- 16296584
TI  - [Effects of alendronate on the markers of bone metabolic activity in
      postmenopausal women with osteoporosis].
AB  - INTRODUCTION: Bisphosphonates are synthetic compounds used in treatment of
      osteoporosis and inhibition of bone resorption. MATERIAL AND METHODS: The
      research included a group of 30 postmenopausal women with osteoporosis, treated
      with alendronate (70 mg per week--Fosamax tablets in combination with calcium and
      active vitamin D--Alpha D3 0.25mcg). The control group included 20 women with
      osteoporosis treated with hormone substitution therapy (HST), calcitonin and deca
      duraboline. Bone metabolic activity, was evaluated using osteocalcin for bone
      formation and cross-laps for bone resorption. Blood samples were taken before
      therapy and 6-8 weeks after. RESULTS: The serum levels of osteocalcin and cross
      laps during application of alendronate were statistically significantly lower
      comparing to those in pre-therapy. The serum levels of osteocalcin and cross-laps
      during the therapy applied in the control group were statistically
      insignificantly lower than values in pre-therapy. Osteocalcin has a tendency of
      decreasing in both groups, and it was slightly more evident in alendronate group.
      Cross-laps demontrated the same tendency of decreasing in both groups, and it was
      more evident in alendronate group. DISCUSSION: Our results have shown the
      efficacy of alendronate in preventing bone loss, which was highly statistically
      significant. They have also shown its suppressive effect on bone formation and
      resorption, but the effects were statistically less significant. CONCLUSION:
      Alendronate significantly reduces the level of bone resorption in postmenopausal
      women with osteoporosis. Its effects on bone formation are less expressed
      Alendronate's effects on bone metabolism become evident not later than 6-8 weeks
      after therapy application. Parameters of bone metabolic activity are very useful
      diagnostic means in evaluation of alendronate effect on bone metabolic activity
      and in the prognosis of bone mass loss.

PMID- 16296585
TI  - [Dysphagia aortica--case report].
AB  - INTRODUCTION: Dysphagia aortica is a swallowing condition caused by external
      compression of the esophagus due to aortic aneurysm or atherosclerotic changes
      affecting the aorta. The case report on this rare cause of dysphagia should
      contribute to better diagnosis of dysphagia aortica and swallowing difficulties
      in general. CASE REPORT: A 63-year-old male patient was hospitalized duo to a
      four month history of intermittent swallowing difficulties. Chest radiography
      showed a widened mediastinum and an enlarged aortic arch. Rigid esophagus
      endoscopy was done in general endotracheal anesthesia. At 28 cm from the upper
      incisors, a difficulty in passing the endoscope appeared, revealing an external
      compression as a probable cause, since the whole esophagus had no intraluminal
      pathological changes. Contrast esophagography revealed an aortic aneurysm. The
      esophagus had a normal lumen width, wall tension and elasticity, and smooth
      contours. After cardiovascular examination and magnetic resonance imaging, a
      giant aneurysm of the aortic arch was diagnosed. DISCUSSION: Patients with
      dysphagia aortica as well as patients with any other swallowing difficulties
      should be managed by multidisciplinary "dysphagia team". The team should include
      an otorhinolaryngologist, neurologist, radiologist, gastroenterologist, surgeon,
      dietitian, speech and language therapist and specially trained nurses.
      CONCLUSION: Aneurysm of the thoracic aorta is a very rare cause of dysphagia.
      Mild to moderate symptoms can be in great disproportion with the severe condition
      which causes them.

PMID- 16296586
TI  - [Jejuno-jejunal intussusception in adults secondary to submucosal leiomyoma].
AB  - INTRODUCTION: Intussusception is the invagionation of a segment of the intestine
      into itself. It is a serous condition that most commonly affects infants and
      children, but can also occur in adults. Intussusception in adults is usually
      caused by tumors, benign or malignant. Early diagnosis is essential to avoid
      treatment delays, which can increase morbidity and mortality. In older patinets
      and adolescents the diagnosis can be complicated due to lower incidence and
      variable subacute symptoms. CASE REPORT: We report a rare case of a 27-year-old
      patient with increasing abdominal discomfort over several weeks. The patient
      experienced increasing colics, recurrent vomiting, dehydration and weight loss.
      Finally he was transferred to the surgical ward of our hospital. Intussusception
      of the small bowel was diagnosed by CT examination. Laparotomy revealed a
      jejunojejunal intussusception caused by a small bowel tumor. CONCLUSION: The
      tumor in the jejunum, almost completely obstructed the intestinal lumen and it
      was resected and bowel continuity was restored. Histopathological examination
      revealed a submucosal leiomyoma of the jejunum.

PMID- 16296587
TI  - [Primary hypothyroidism associated with empty sella turcica and hypopituitarism].
AB  - INTRODUCTION: Empty sella syndrome is a rather frequent neuroradiological finding
      in the general population and can be associated with hypopituitarism.
      Examinations reveal low pituitary hormone levels and lack of response to stimuli.
      Most patients suffer from central hypothyroidism as part of pituitary
      insufficiency. Primary hypothyroidism is a rare finding in these patients. CASE
      REPORT: We present 3 patients: one female and two male, suffering from complete
      hypopituitarism, as part of the empty sella syndrome diagnosed due to low
      concentrations of all pituitary hormones, elevated TSH and low thyroid hormones.
      TRH, LHRH, ACTH and ITT tests, as well as IGF1 have confirmed hypopituitarism and
      primary hypothyroidism. CT and NMR in all three patients showed empty sella
      without a tumor in it. The diagnosis of primary hypothyrodism in the first
      patient was made before hypopituitarism has taken place, or at the same time in
      the second patient, whereas in the third patient it was diagnosed twenty years
      later. In two patients anti-TPO and anti-Tg antibody levels were high, and in the
      third patient they were not elevated. It can be assumed that the etiology of
      primary hypothyrodism in all three patients was of autoimmune origin, which
      caused thyroid hypofunction. High level of TSH in all three patients and
      especially in the patient whose hypopituitarism was diagnosed twenty years later,
      showed presence of thyrotrophic cells in the pituitary. Evaluation of the
      hypothalamic-pituitary-thyroid axis was carried out during the complete
      substitution therapy of hypopituitarism. CONCLUSION: Diagnosing primary
      hypothyroidism associated with hypopituitarism helps improving the knowledge on
      empty sella syndrome and points to different clinical syndromes characterized by
      lack of mixoedema, although approach to therapy is the same for both primary and
      central hypothyroidism.

PMID- 16296588
TI  - [Native and contrast radiographic examination of the urinary tract].
AB  - INTRODUCTION: Plain x-rays and contrast urography are important for diagnosing
      urinary tract diseases. The first plain film of the urinary tract was made in
      1896, and the first tests using contrasts started in 1904. Excretory urography
      has been used since 1930. PLAIN FILM OF THE URINARY TRACT: Plain films of the
      urinary tract are used in the kidney area, the area of the ureter and urinary
      bladder. They also show structures (lumbar and sacral spine and pelvis), muscles
      (m. iliopsoas) as well as calculi. EXCRETORY UROGRAPHY: X-ray visualization of
      the urinary tract with contrast substances is intravenous urography. It is used
      for diagnosing diseases of the upper urinary system with symptoms such as: pain,
      colic, hydronephrosis, as well as acute cortical infections, urinary bladder
      tumors, etc. RETROGRADE UROGRAPHY: Retrograde urography is a procedure
      recommended when either the pyelocalyx system or the ureter are not seen
      unilaterally or bilaterally. CYSTOGRAPHY AND URETHROCYSTOGRAPHY: Cystography is
      used to visualize the bladder. It is recommended in case of intravesical
      obstruction. Urethrocystography is a technique for investigation of the anterior
      and prostatic urethra as well as the neck of the urinary bladder.

PMID- 16296589
TI  - [Famous physicians from the Simonovic family].
AB  - The prominent Simonovic family, from its earliest ancestors known for seeking and
      promoting education and holding key positions in the society, is known for
      several remarkable intellectuals, cultural and public workers, as well as
      physicians. They were all exceptional in their own way, contributing to national
      education and their professions, and not by accident. This paper presents
      personal lives and professional careers of three brothers, physicians from the
      Simonovic family: Dr. Radivoj Simonovic, a famous physician from Sombor who was
      also a historian, ethnographer, mountaineer, geomorphologist, photoamateur and a
      medical educator, Dr. Milan Simonovic, for many years beloved and well-known
      physician in Petrovaradin, and Dr. Svetislav Simonovic, esteemed physician in
      Belgrade who was the personal physician to King Petar Karadordevic. Apart from
      their family heritage, their scientific and professional achievements are
      certainly a result of their talents, training and discipline.

PMID- 16296590
TI  - High earning in the practice of family medicine.

PMID- 16296591
TI  - High earning in the practice of family medicine.

PMID- 16296592
TI  - High earning in the practice of family medicine.

PMID- 16296593
TI  - High earning in the practice of family medicine.

PMID- 16296594
TI  - Homogenized lemmings.

PMID- 16296595
TI  - An EHR user-satisfaction survey: advice from 408 family physicians.

PMID- 16296596
TI  - Get better results with staff performance standards.

PMID- 16296598
TI  - A must-do list for the departing physician.

PMID- 16296597
TI  - Don't get burned coding common skin procedures.

PMID- 16296599
TI  - Reliability science: reducing the error rate in your practice.

PMID- 16296600
TI  - Coding nonsense, NOS.

PMID- 16296601
TI  - [Screening of a hepatic stellate cells subtracted cDNA library of differentially
      expressed genes in mice with schistosomiasis japonica].
AB  - OBJECTIVE: To construct and screen a hepatic stellate cells(HSCs) subtracted cDNA
      library, in order to seek differentially expressed genes in mice infected with
      Schistosoma japonicum. METHODS: HSCs were isolated from mouse as targets, and
      cDNA fragments of normal mouse were compared to those of S. japonicum infected
      mice to find dif ferentially expressed genes by technique of suppression
      subtractive hybridization(SSH). Differentially expressed cDNA fragments were then
      directly inserted into T/A cloning vector to set up the subtractive library.
      Amplification of the library was carried out with transformation of DH5alpha. A
      subtracted cDNA library was constructed and then hybridized with forward and
      backward subtracted probes for differential screening. One hundred positive
      bacterial clones were randomly selected for se quenching and BLAST analysis.
      Finally, virtual Northern blot confirmed such differential expression. RESULTS:
      The amplified library contained more than 400 positive bacterial clones. Random
      analysis of 100 clones with restriction enzyme digestion showed that all clones
      contained 200-600 bp inserts. 76 ESTs were obtained with 70 related to fibrosis
      caused by schistosomiasis or other etiological factors. Other 6 ESTs were not
      found in PubMed. CONCLUSION: The subtracted cDNA library of differentially
      expressed genes of HSC in normal mice and schistosome-infected mice was
      constructed successfully with SSH and T/A cloning techniques.

PMID- 16296602
TI  - [Epidemiological trend of malaria in children under 10 in a town of Xiaochang
      County in 5 years].

PMID- 16296603
TI  - [Study on a grey model for evaluation of Anopheles minimus density].
AB  - OBJECTIVE: To establish Anopheles minimus density evaluation model based on
      climate, environmental and remote sensing data. METHODS: 27 townships in 10
      counties of Yunnan Province were chosen as field spots. Data on climate,
      environment, remote sensing and An. minimus density were collected from 1984 to
      1993. Grey correlation analysis was carried out to study the relationship of 18
      indices with An. minimus density. E variable was developed and its relation to
      the An. minimus density was analyzed to establish an evaluation model. RESULTS:
      Eight indices were selected based on a grey threshold 0.70: Dry season average
      temperature > dry season temperature(min) > wet season temperature(min) > wet
      season NDVI > wet season average temperature > the ratio of paddy field in total
      arable land > dry season temperature(max) > wet sea son temperature(max). The An.
      minimus density evaluation model was derived as follows: [formula: see text] The
      correct rate of evaluation by the model was 92.0%. e0.5 = 18%, with an average
      relative error of 21%. CONCLUSION: A quasi-evaluation on the An. minimus density
      can be made by applying the grey model.

PMID- 16296604
TI  - [A case of echinococcosis granulosus reported in Qujing City of Yunnan].

PMID- 16296605
TI  - [Transformation of schistosomulae by electroporation and transient expression of
      the enhanced green fluorescent protein (EGFP) gene].
AB  - OBJECTIVE: To explore the possibility of heterogeneous gene to express in
      juvenile Schistosoma japonicum and the application of electroporation in
      transformation of schistosomulae. METHODS: The plasmids of pEGFP-C1 were
      introduced into mechanically transformed schistosomula with electroporation. The
      presence, transcription and translation of the transgene in electroporated
      schistosomula were confirmed by PCR, RT-PCR and Western blotting analysis
      respectively using the genomic DNA, total RNA and protein extracted and isolated
      from schistosomula cultured in vitro for 48 hours. Meanwhile, localization of
      EGFP within electroporated schistosomula was performed with confocal laser
      scanning micro scope. RESULTS: 760 bp and 276 bp amplified products by PCR and RT
      PCR were found coincident with the expected size and expression of EGFP gene in
      electroporated schistosomula was confirmed by Western blotting. Fluorescence of
      EGFP was localized in tegument and subtegument of the electroporated
      schistosomula with confocal microscopy, especially in the anterior part of the
      worm. CONCLUSION: The heterogeneous gene of EGFP has been successfully introduced
      into juvenile S. japonicum by electroporation and the expression of transgene was
      confirmed with molecular and microscopical methods.

PMID- 16296606
TI  - [Purification of the effective component from Solanum xanthocarpum and its effect
      against Oncomelania snails].
AB  - OBJECTIVE: To extract and purify the active component from Solanum for
      Oncomelania snail control, evaluate its effect against the snails and determine
      its chemical structure. METHODS: Pedicel and seed were moved and the remaining
      part of the Solanum xanthocarpum fruit was torrefied and ground into powder. The
      powder was soaked into 95% ethanol and extracted. The residue was treated by
      ethyl acetate. 7 components were separated by methods of thin layer
      chromatography (TLC) and column chromatography (CCL). 4 main components were
      observed for the effect of snail-killing by immersion method. An alkaloid with Rf
      = 0. 58, named as component A, was confirmed as one of the effective components
      for Oncomelania snail control. The component A was further purified and received
      Al and A2 by proper elusion, and their effect was re-tested. The molecular weight
      and chemical structure of A2 were determined by MS, NMR and IR respectively.
      RESULTS: The death rate of Oncomelania snails was 94.2% when the concentration of
      component A was 2.50 mg/L1(28 C ). The flow liquid system (ethyl acetate:
      chloroform: methanol 11:11:35) applied was the best reagent for separating
      component A. The death rate of Oncomelania snails in solution of A2 (0.2 mg/L)
      was 100% (28 degrees C). The molecular weight of A2 was 867 with an mp 298-305 C.
      CONCLUSION: The effective agent (A2),one of the active components from the fruit
      of Solanum xanthocar pum, is alpha-solamargine which shows an excellent effect in
      killing Oncomelania snails.

PMID- 16296607
TI  - [Preparation and preliminary application of monoclonal antibodies against adult
      worm of Angiostrongylus cantonensis].
AB  - OBJECTIVE: To develop and identify monoclonal antibodies (McAbs) against adult
      worm of Angiostrongylus cantonensis and observe its applicability. METHODS:
      BALB/c mice were immunized with soluble antigen of adult worms of A. cantonensis.
      The spleen cells of immunized mice were fused with myeloma cell, and the
      hybridoma secreting high titer of McAbs with high specificity was screened. By
      using the McAbs, serum of angiostrongyliasis patient and sera of the rats
      infected with A. cantonensis were detected by Western blotting and double
      antibody sandwich ELISA respectively. RESULTS: Three McAbs were established (2A2,
      3F1, 4H2), which all showed no cross reaction with antigens of Schistosoma
      japonicum, Paragonimus westermani, Cysticercus cellulosae and Trichinella
      spiralis. Western blotting analysis demonstrated that the three McAbs recognized
      a Mr 15,000 soluble antigen of adult worm of A. cantonensis and recognized the Mr
      24,000 and Mr 15,000 circulating antigens from the serum of angiostrongyliasis
      patient. The double antibody sandwich ELISA detection showed a positive rate of
      76.5%. CONCLUSION: Three hybridoma cell lines against adult worm of A.
      cantonensis have been established which secret high titer of McAbs with high
      specificity and seem promising in detecting the circulating antigen of the
      angiostrongyliasis patient.

PMID- 16296608
TI  - [Preparation of monoclonal antibodies specific to lactate dehydrogenase of
      Plasmodium falciparum].
AB  - OBJECTIVE: To prepare monoclonal antibodies specific to lactate dehydrogenase of
      Plasmodium falciparum. METHODS: The Plasmodium falciparum lactate dehydrogenase
      (pLDH) gene was amplified from whole blood of malaria patients by PCR and cloned
      into expression vector pGEX-3X. Recombinant pLDH protein was expressed and
      purified, and used for immunizing mice to prepare monoclonal antibodies (McAbs).
      The McAbs were characterized by Western blotting analysis. RESULTS: The
      Plasmodium falciparum lactate dehydrogenase gene was amplified and cloned into ex
      pression vector pGEX-3X. The recombinant pLDH plasmid was expressed in E. coli)
      BL-21 cells. 15 cell lines of McAbs with high titer against pLDH were obtained
      using the recombinant pLDH as immunogen. Western blotting analysis showed that
      these McAbs recognized a Mr 33,000 of native Plasmodium falci parvum protein
      without cross reaction with constituents of red blood cell of febrile patients
      from endemic area of malaria. CONCLUSION: Fifteen hybridoma cell lines secreting
      high titer of McAb specific to Plasmodium falciparum LDH were established based
      on the recombinant pLDH.

PMID- 16296609
TI  - [Gastric myiasis caused by the larvae of Fannia canicularis].

PMID- 16296611
TI  - [A survey on the prevalence of important human parasitic diseases in Qinghai
      Province].

PMID- 16296610
TI  - [Consistency analysis in the use of abdominal ultrasonography for diagnosing
      schistosomiasis japonica-related morbidity].
AB  - OBJECTIVE: To explore the consistency among different indices of abdominal
      ultrasonography for the diagnosis of schistosomiasis japonica related morbidity
      and the best combination of the indices. METHODS: Six indices of abdominal
      ultrasonography were selected to investigate schistosomiasis related morbidity in
      residents in a village of Hunan Province, and the Kappa coefficients of
      diagnostic consistency among different indices and Cronbach's alpha coefficients
      of different combinations of indices were computed. RESULTS: The Kappa
      coefficients of 'liver parenchyma > or = grade II' with 'right midclavicular
      subcostal' and with 'portal vein diameter' were 0.4131 and 0.4655 respectively,
      higher than normal level. The degree of their consistency was fair, and others
      showed poor or almost no consistency. Among the combinations made up of different
      indices, the Cronbach's alpha coefficient of the combination made up of 'liver
      parenchyma > or = grade II', 'right midclavicular subcostal' and 'portal vein
      diameter' was 0.6566 which was the highest, showing the strongest internal
      consistency. CONCLUSION: The six indices can not be replaced with each other in
      assessing schistosomiasis related morbidity. Before abdominal ultrasonography is
      used extensively to assess the morbidity, it is necessary to study the diagnostic
      consistency of these indices and the best combination of the indices.

PMID- 16296612
TI  - [Experimental and clinical studies on the effect of sodium dodecylbenzene
      sulfonate in in vitro killing Demodex and in treating demodicidosis].
AB  - OBJECTIVE: To observe the effect of sodium dodecylbenzene sulfonate (SDBS) in
      killing Demodex in vitro and in the treatment of demodicidosis. METHODS: (1) The
      experiment of in vitro killing Demodex with 1% and 2% SDBS was conducted. (2) A
      clinical trial was carried out to evaluate the therapeutic effect in the
      treatment of demodicidosis with 2% SDBS and 2% metronidazole emulsion. Patients
      with demodicidosis were randomly divided into trial and control groups (31 cases
      each). They were treated with 2% SDBS ointment and 2% metronidazole ointment
      twice a day in the early morning and evening respectively for eight weeks
      consecutively. Inflammatory lesions of face, Demodex infestation and scores of
      erythema were measured to evaluate the effect before and after treatment. (3)
      Follow-up was carried out for two months to evaluate the effect and side effects
      after 8 weeks' treatment. RESULTS: (1) 2% SDBS killed all Demodex in vitro after
      5 h, there was significant difference between the 2% SDBS and 2% metronidazole
      (69.4%), or between SDBS and peanut oil (9.1%) (P < 0.05). There was no
      significant difference in killing Demodex folliculorum and Demodex brevis with 2%
      SDBS. (2) Clinical observation showed that there was a significant difference in
      facial inflammatory lesions, Demodex infestation and scores of erythema before
      and after treatment with 2% SDBS (P < 0.05). The effective rate was 87.1%, 65.5%
      in 2% SDBS group and 2% metronidazole group respectively, with a significant
      difference between the two groups (P < 0.05). Follow up showed same results. (3)
      A slight burning sensation was the only side-effect in 3 cases with 2% SDBS
      ointment. CONCLUSION: Sodium dodecylbenzene sulfonate has the effect of in vitro
      killing Demodex and is highly effective in the treatment of demodicidosis.

PMID- 16296613
TI  - [Preliminary survey on concentration of indoor allergens derived from dust mites
      in residential homes in Shanghai].
AB  - OBJECTIVE: To investigate the level of indoor dust mite allergens in residential
      homes in Shanghai. METHODS: The allergenic proteins, Dff F3 and Der f III (well
      known allergen) from the whole culture extract of Dermatophagoides farinae were
      purified by chromatography and sedimentation techniques. Allergic activities of
      both proteins were identified by skin prick test and RAST. After preparation of
      specific IgG anti-Dff F3, anti-Der f III, and extraction of indoor allergens from
      200 indoor dust samples collected from residential homes, the allergen
      concentration was measured by sandwich ELISA. Allergen level was expressed in
      geometric mean and range, the analysis of variance (ANOV) was used to determine
      the level of significance between groups. RESULTS: Dff F3 and Der f III were
      demonstrated strongly allergic activities, which can be highly recognized with
      IgE from sera of the mite-allergic patients with asthma. In the sampled 200
      homes, the proportion of homes with Dff F3 level of >10 microg/g was 57.0%, 29.5%
      for group of 2-10 microg/g, and 13.5% for group of <2 microg/g. The proportion of
      homes with Der f III level of >10 microg/g was 53.5%, 32.0% for group of 2-10
      microg/g, 14.5% for group of <2 microg/g. CONCLUSION: Selected residential homes
      in Shanghai were found more likely to have high level of dust mite allergens. Dff
      F3 was identified as the stronger allergic fraction.

PMID- 16296614
TI  - [Preparation of DNA from Cryptosporidium parvum oocysts for PCR detection].
AB  - OBJECTIVE: To establish three methods of DNA extraction from Cryptosporidium
      parvum oocysts and test by PCR. METHODS: After three freeze-thaw cycles, three
      kinds of templates were extracted from the oocysts by Chelex-100,
      phenol/chloroform or genomic DNA purification system kit, and used for PCR
      detection. According to the sequence of a C. parrum gene (L.16996), a pair of
      primers was designed and synthesized, and used for PCR. The sensitivity of the
      template by Chelex 100 method was also tested by PCR. RESULTS: One 446 bp PCR
      product was observed by agarose gel electrophoresis for all three kinds of
      templates. The PCR sensitivity by Chelex-100 extracted DNA reached for detection
      of a specimen containing only 1/2 oocyst. CONCLUSION: The three kinds of
      extraction can all be served as templates for PCR detection of C. parvum oocysts,
      while Chelex 100 method is simpler, quicker and more reliable for DNA extraction
      of the parasite.

PMID- 16296616
TI  - [A case of Thelazia callipaeda infection].

PMID- 16296615
TI  - [Purification, enzyme activity and immunology study of recombinant protein
      glyceraldehyde-3-phosphate dehydrogenase of Clonorchis sinensis].
AB  - OBJECTIVE: To produce prokaryotic recombinant protein glyceraldehyde-3 phosphate
      dehydrogenase of Clonorchis sinensis (CsGAPDH), analyze its enzyme activity and
      immunological function. Methods The recombinant CsGAPDH was purified according to
      the protocol of GST-Bind kit and was digested with thrombin proteinase and eluted
      with wash buffer. The BALB/c mice were inoculated with the purified protein. The
      antisera collected from the mice were used to detect the titres of IgG antibodies
      by ELISA, and Western blotting was used to identify the specificity of the
      antisera with the purified CsGAPDH. S-P immunohistochemistry method was used to
      confirm the expression and distribution of CsGAPDH in adult Clonorchis sinensis
      with the polyclonal antibodies from immunized BALB/c mice. The CsGAPDH catalytic
      activity was evaluated employing the conventional substrate glyceraldehyde-3
      phosphate (3-GAP). RESULTS: SDS-PAGE showed a single purified protein band. Gel
      scanning analysis revealed that the protein purity of CsGAPDH was 90%. ELISA
      analysis showed an increased IgG value. S-P immunohistochemistry analysis
      demonstrated that the recombinant plasmid pGEX-4T-1 GAPDH expressed and
      distributed in muscle cell membrane of immune mice. Western blotting result
      suggested that CsGAPDH protein contained essential epitopes with high antigenic
      activities. This protein CsGAPDH could catalyzed 3-GAP with enzymatic active unit
      of 2872 U min(-1) ml(-1). CONCLUSION: The recombinant protein CsGAPDH shows a
      proper enzymatic activity and immunogenicity.

PMID- 16296617
TI  - [Construction and expression of the Ts87 gene of Trichinella spiralis in Pichia
      pastoris].
AB  - OBJECTIVE: To construct the recombinant plasmid P(PICZ) alphaA-Ts87 and obtain
      secretive protein in Pichia pastoris. METHODS: Ts87 was amplified by PCR and
      cloned into the expression vector P(PICZ) alphaA of P. pastoris to form P(PICZ)
      alphaA-Ts87. After the recombinant was isolated and linearized, it was
      transformed into P. pastoris GS115 by EasyComp kit and screened for zeocin
      resistant with different conditions and Mut phenotype. The high resistant Mut+
      clones were cloned and the product induced by methanol was tested by dot
      hybridization. The expression product was further identified by SDS-PAGE and
      Western blotting. RESULTS AND CONCLUSION: The recombinant plasmid P(PiCZ) alphaA
      Ts87 has been constructed. Ts87 gene has been expressed and secreted in Pichia
      pastoris GS115 strain.

PMID- 16296618
TI  - [An important case of vivax malaria from Pakistan].

PMID- 16296619
TI  - [Gimenez staining: a rapid method for initial identification of legionella
      pneumophila in Amoeba trophozoite].
AB  - OBJECTIVE: To establish a rapid staining method for facilitating initial
      identification of Legionella pneumophila in amoebal trophozoite. METHODS:
      Acanthamoeba polyphaga and Legionella pneumophila were co-cultured under
      laboratory condition. At consecutive time points during the culture, smears of
      the cultured products were made on glass slides for staining purposes. Different
      types of stainings including Gram's staining, Gimenez staining, Giemsa staining
      and immunofluorescence were used to determine the best method for the
      identification of amoebal pathogens. RESULTS: Gimenez staining technique is
      simpler and yields better results as compared with the other three stainings.
      Gimenez stain gives the best color and contrast for amoeba and amoebal Legionella
      Amoeba trophozoites and/or cysts showed a distinct purplish blue with amoebal
      Legionella in red. Amoebal Legionella can be distinguished clearly at an earlier
      time of co cul ture, providing a proper sensitivity. It takes only 10 minutes to
      finish the operation. The other techniques require the use of expensive reagents,
      are relatively time-consuming, and involve complex staining procedures.
      CONCLUSION: Gimenez staining is of value for the initial identification of
      amoebal pathogens, and it is suitable for laboratory diagnosis.

PMID- 16296620
TI  - [On the taxonomic status of Anopheles anthropophagus and Anopheles lesteri from
      China (Diptera: Culicidae)].

PMID- 16296621
TI  - [A reform practice on teaching and experiment of human parasitology].

PMID- 16296622
TI  - [Advances in gender-specfically expressed genes of parasitic nematodes].

PMID- 16296623
TI  - [Research progress on iron chelator for malaria therapy].

PMID- 16296625
TI  - [An investigation of facial Demodex infection among college students in Qingdao
      area].

PMID- 16296624
TI  - [Clinical analysis on clonorchiasis patients in Huainan area].

PMID- 16296626
TI  - [High intensity focused ultrasound treatment in a case of giant hepatic
      echinococcosis multilocularis].

PMID- 16296628
TI  - Global 2005 health. The paths of infection.

PMID- 16296627
TI  - Saving 1 life at a time.

PMID- 16296629
TI  - 18 heroes.

PMID- 16296630
TI  - Riches to the poor.

PMID- 16296631
TI  - Beating cancer.

PMID- 16296633
TI  - [Nonconventional therapies in cancer].
AB  - This paper describes the therapeutic complementation carried out by cancer
      patients, assisted at 4 hospitals of Buenos Aires City. The authors propose to
      classify non conventional medicines, taking into account the sociocultural and
      historical context of Argentina. These categories discriminate among
      complementary/alternative medicines (CAM), self-treatment, traditional medicines
      (TM), and religious healing. The unit of analyses was a sample of 200 patients.
      The information was collected in semi-structured and open interviews. Results
      show that 90% of patients consult other medicines, at least once. CAM: 72%, self
      treatment: 97%, TM: 22%, religious healing 42%. Fourty four percent of patients
      with progressive tumor and long duration sickness consulted two or more
      medicines, while only 20% of patients with primary and located cancer consulted
      two or more medicines. The familiarization with traditional medicines is
      associated to the preference for traditional healers; it increases from 22 to 55%
      of the immigrants and patients from inside Argentina and neighboring countries.
      Taking into account religious identity, it was noted that pentecostals and
      evangelists without exception consulted their own therapeutic rituals and
      rejected traditional medicine. Among catholics, 75% prefer their own religious
      offering and 25% other religious practices, and do not reject traditional
      medicines because of religious factors. There were no differences in gender or
      age.

PMID- 16296632
TI  - [Cardiovascular risk factors in children with type 1 diabetes and their
      relationship with the glycemic control].
AB  - Diabetics have an increased risk of cardiovascular disease (CVD). The objective
      of this work was to evaluate the cardiovascular risk factors in infant-juvenile
      type 1 diabetics and their association with the degree of glycemic control. A
      total of 52 patients, aged 5-15 years, were studied and compared with 37 control
      subjects. The degree of glycemic control, lipid profile, plasma fibrinogen,
      microalbuminuria and blood pressure were investigated. The patients were grouped
      in diabetics with good glycemic control [DGGC, glycosilated hemoglobin (HbA1c) <
      8%] and poor glycemic control [DPGC, HA1c > or = 8%]. Diabetic patients presented
      incremented values of total cholesterol (4.1 +/- 0.9 vs. 3.1 +/- 0.7 mmol/l, p =
      0.0008), LDL-cholesterol (2.4 +/- 0.9 vs. 1.7 +/- 0.7 mmol/l, p = 0.0001), HDL
      cholesterol (1.2 +/- 0.3 vs. 1.0 +/- 0.2 mmol/l, p = 0.0002), with respect to
      control group. Eighty three per cent of diabetics showed a poor glycemic control.
      There were not significant differences in lipid profile between DGGC and DPGC,
      excepting HDL-cholesterol which was higher in DPGC group (p = 0.007). Plasma
      fibrinogen levels were similar in diabetics and controls, but they were higher in
      DPGC than in DGGC (265 +/- 46 vs. 229 +/- 22 mg/dl, p = 0.02). Three patients
      with microalbuminuria and none with hypertension were detected. In these patients
      the most pronounced risk factors for CVD were dyslipidemia and hyperglycemia,
      which justify the need for the early detection of these factors as well as strict
      metabolic control.

PMID- 16296634
TI  - Postdiarrheal Shiga toxin-mediated hemolytic uremic syndrome similar to septic
      shock.
AB  - The inflammatory response of host endothelial cells is included in the
      development of vascular damage observed in enterohemorrhagic Escherichia coli
      (EHEC) infection, resulting in hemolytic uremic syndrome (HUS). The response to a
      non-conventional treatment for a group of D+ HUS (diarrhea positive HUS)
      patients, with clinical hemodynamic parameters of septic shock was evaluated in
      this prospective study (1999-2003). Twelve children 2.8 +/- 0.6 years old, with
      D+ HUS produced by E. coli infection with serological evidence of Shiga toxin,
      presenting severe unstable hemodynamic parameters and neurological dysfunction at
      onset, were studied. The protocol included fresh frozen plasma infusions,
      methylprednisolone pulses (10mg/k/day) for three consecutive days and plasma
      exchange for five days, starting after admission to the intensive care unit
      (ICU). The twelve patients with increased pediatric risk of mortality (PRISM)
      score: 18 +/- 2 after admission to intensive care unit (ICU), required dialysis
      for 17.4 +/- 4 days, mechanical ventilator assistance for 10 +/- 1 days and early
      inotropic drugs support for 10.5 +/- 1 days. Neurological dysfunction included
      generalized tonic-clonic seizures lasting for 5.4 +/- 1 days, n:8. Focal seizures
      were present in the remaining patients. Dilated cardiomyopathy was present in 6
      children. Eight children suffered hemorrhagic colitis. Nine patients survived.
      Within one year of the injury, neurological sequelae, Glasgow outcome scale (GOS)
      3 and 4, were present in two patients, chronic renal failure in one patient. We
      suggest that early introduction of this protocol could benefit D+ HUS patients
      with hemodynamic instability and neurological dysfunction at onset. Further
      studies are likely to elucidate the mechanisms involved in this early adverse
      clinical presentation of D+ HUS patients.

PMID- 16296635
TI  - [Evolution of children one year post liver transplant].
AB  - Orthotopic liver transplantation is the only definitive mode of therapy for
      children with end-stage liver disease. However, it remains challenging because of
      the necessity to prevent long-term complications. The aim of this study was to
      analyze the evolution of transplanted patients with more than one year of follow
      up. Between November 1992 and November 2001, 238 patients underwent 264 liver
      transplantations. A total of 143 patients with more than one year of follow up
      were included. The median age of patients +/- SD was 5.41 years +/- 5.26 (r: 0.58
      21.7 years). All children received primary immunosuppression with cyclosporine.
      The indications for liver replacement were: fulminant hepatic failure (n: 50),
      biliary atresia (n: 38), cirrhosis (n: 37), chronic cholestasis (n: 13) and
      miscellaneous (n: 5). The indications for liver re-transplantation were: biliary
      cirrhosis (n: 7), hepatic artery thrombosis (n: 4) and chronic rejection (n: 3).
      Reduced-size liver allografts were used in 73/157 liver transplants, 14 of them
      were from living-related donors and 11 were split-livers. Patient and graft
      survival rates were 93% and 86% respectively. Death risk was statistically higher
      in retransplanted and reduced-size grafted patients. Growth retardation and low
      bone density were recovered before the first 3 years post-transplant. The
      incidence of lymphoproliferative disease was 7.69%. De novo hepatitis B was
      diagnosed in 7 patients (4.8%). Social risk did not affect the outcome of our
      population. The prevention, detection and early treatment of complications in the
      long-term follow up contributed to improve the outcome.

PMID- 16296636
TI  - [Early urinary tract infection in kidney transplantation. Risk factors and impact
      on graft survival].
AB  - The early urinary tract infection (EUTI) in kidney transplant recipients is an
      infection develop during the first 3 months post transplant surgery. The effect
      of EUTI on graft survival and risk factors have been scarcely studied. Our
      objetives were the evaluation of risk factors to EUTI, the assessment of the
      causal agent and graft survival impact. A retrospective analysis of kidney
      transplantation, period 1997-2000 in Hospital Privado-Centro Medico de Cordoba
      was carried out. There were two groups of patients with (EUTI group) and without
      EUTI (control group). Cox model was used to analyze risk factors and Kaplan-Meier
      method for graft survival. A total of 226 consecutive patients received kidney
      transplantation. In 55 patients (24.3%) EUTI was detected. Risk factors for EUTI
      were: invasive urological maneuvers (RR = 4.34, CI 95% 1.42-13.21), diabetes
      mellitus (RR = 3.79, CI 95% 1.42-10.14), cytomegalovirus infection (RR = 2.9, CI
      95% 1.02-8.24) and previous transplants (RR = 2.83, CI 95% 1.08-7.45). Delayed
      graft function was associated with lower incidence of EUTI (RR = 0.38, CI 95%
      0.15-0.94). The causal agents were: Klebsiella pneumoniae (36%), Pseudomonas
      aeruginosa (24%) and Escherichia coli (9%). Graft survival at 2 years was similar
      in EUTI (87.2%) and control group (81.2%, p = 0.32). This series shows that
      invasive urological maneuvers were the main risk factors for EUTI. Graft survival
      was similar. High prevalence of non coli bacteria need further evaluation.

PMID- 16296637
TI  - [Takotsubo, reversible apical ballooning of the left ventricle. Report of 4
      cases].
AB  - A syndrome of apical ballooning, with ECG mimicking acute myocardial
      infarctation, mild or no enzymatic changes, and normal coronary angiogram was
      described in 1990. It presents mainly in middle aged and elderly women and it is
      preceded by stress triggering circumstances. Several mechanisms have been
      proposed although the precise cause remains unclear. The most accepted theory
      proposes the interaction of catecholamines and an inadequate inotropic response.
      We report four cases that presented with chest pain and sudden onset of heart
      failure, all patients had physical or emotional stress as a triggering factor. On
      ECG, ST segment elevation and inverted T waves were observed in the acute phase.
      All patients had typical echocardiogram image and normal coronary angiogram. Both
      ECG and echocardiogram returned to normal within two weeks.

PMID- 16296638
TI  - [Mantle cell lymphoma vs. atypical chronic lymphocytic leukemia. Use of
      immunohistochemistry, flow cytometry and molecular biology for their adequate
      typing].
AB  - The differential diagnosis of certain B CD5+ lymphoproliferative processes, such
      as mantle cell lymphoma (MCL) and atypical chronic lymphocytic leukemia (ACLL),
      is difficult. The aim of this study was to correlate morphological findings,
      cyclin D1 (cD1) detection by immunohistochemistry (IHC) and immunophenotype by
      flow cytometry (FC) with the results obtained by molecular biology in this type
      of neoplasias. We analyzed 20 samples classified as B CD5+ lymphoproliferative
      processes by FC. PCR was used for t(11;14) bcl-1/IgH determination.
      Histopathological and IHC studies for cD1 were done in 14 cases. Twelve cases
      were diagnosed as MCL, with positive cD1 in 5 (5/9), five as ACLL and three as B
      lymphoproliferative process. PCR revealed t(11;14) in 6/12 MCL and negative
      results in the other groups (0/8). Molecular biology evidenced translocation in
      4/5 MCL positive for cD1 with IHC. The presence of translocation could be
      demonstrated by IHC and PCR in 7/12 MCL: 4 with both techniques, 2 with PCR
      alone, and 1 with IHC alone. These findings show a significant association
      between cD1 by IHC and bcl-1/ IgH gene detection by PCR, which implies that both
      techniques are complementary for MCL typing.

PMID- 16296639
TI  - [Regional transient osteoporosis, and reflex sympathetic dystrophy: the same
      disease?].
AB  - Complex regional pain syndrome, reflex sympathetic dystrophy, regional, transient
      and migratory osteoporosis, are known as a spectrum of medical conditions that
      present with pain, edema, erythema, localized osteoporosis and sometimes
      sympathetic dysfunction. Many factors which are present in these conditions, such
      as clinical presentation, radiologic findings and a variety of still unclear
      physiopathologic mechanisms are correlated. We propose that all these conditions
      are different periods of the same pathology.

PMID- 16296640
TI  - [Ablation by radio-frequency without need of fluoroscopy].

PMID- 16296641
TI  - [Scimitar syndrome].

PMID- 16296642
TI  - [Dyspnea, hypercapnia, pulmonary hypertension and lung infiltration in an elderly
      woman with recently diagnosed breast cancer].

PMID- 16296644
TI  - [Prostate cancer].

PMID- 16296643
TI  - [Argentine consensus of non-invasive ventilation].
AB  - Non-invasive ventilation (NIV) is nowadays increasingly used. The significant
      decrease in tracheal intubation related complications makes it particularly
      attractive in patients with moderately acute respiratory failure (ARF) who still
      have some degree of respiratory autonomy. It has also been used to support
      patients with chronic respiratory failure. However, final outcomes are variable
      according to the conditions which determined its application. This Consensus was
      performed in order to review the evidence supporting the use of positive pressure
      NIV. The patho-physiological background of NIV and the equipment required
      technology are described. Available evidence clearly suggests benefits of NIV in
      acute exacerbation of chronic obstructive pulmonary disease (COPD) and in
      cardiogenic pulmonary edema (Recommendation A). When considering ARF in the
      setting of acute respiratory distress syndrome results are uncertain, unless
      dealing with immunosupressed patients (Recommendation B). Positive results are
      also shown in weaning of mechanical ventilation (MV), particularly regarding
      acute exacerbation of COPD patients (Recommendation A). An improved quality of
      life in chronic respiratory failure and a longer survival in restrictive
      disorders has also been shown (Recommendation B) while its benefit in stable COPD
      patients is still controversial (Recommendation C). NIV should be performed
      according to pre-established standards. A revision of NIV related complications
      is performed and the cost-benefit comparison with invasive MV is also considered.

PMID- 16296645
TI  - [The wonders of hell].

PMID- 16296646
TI  - [A history of William Osler's The Principles and Practice of Medicine].

PMID- 16296647
TI  - [Sir William Osler at McGill].

PMID- 16296648
TI  - [The history of medicine].

PMID- 16296650
TI  - Managing childhood orthopaedic abnormalities.

PMID- 16296649
TI  - [Cyclooxygenase-2 inhibitors and the ethics of research].

PMID- 16296652
TI  - Managing cervical spondylosis.

PMID- 16296651
TI  - Casebook: shoulder pain.

PMID- 16296653
TI  - Diagnosing and treating gout.

PMID- 16296654
TI  - FAQs in hormone replacement therapy.

PMID- 16296655
TI  - A guide to the MRCGP video.

PMID- 16296657
TI  - A whirlwind's winning ways.

PMID- 16296658
TI  - Wiping out TB and AIDS.

PMID- 16296659
TI  - The blueprint of life.

PMID- 16296660
TI  - For a healthier globe.

PMID- 16296661
TI  - Thriving in the zone.

PMID- 16296662
TI  - Drugs for the doctor's bag: 2--children.
AB  - In September 2005, we published Drugs for the doctor's bag: 1--Adults,
      recognising the fact that there is still a need for most GPs to carry well
      equipped bags, even though many have given up responsibility for out-of-hours
      services. Here we suggest medicines that a GP might want to have available for
      use in an emergency or for the acute treatment of children and adolescents,
      updatingour previous advice. As with adults, it is not our intention to imply
      that every GP must carry every drug mentioned. Some of the drugs will probably
      only be used by rural GPs who do not have access to immediate emergency care.
      Whenever a medicine is first mentioned, our suggested formulation is included in
      brackets. Unless otherwise stated, the doses given are all from the BNF for
      Children. We enclose with this issue a card summarising parenteral doses (for
      adults and children) of drugs for medical emergencies; this card includes the BNF
      table of ideal weight for age.

PMID- 16296663
TI  - The BNF for children.
AB  - Many medical conditions, treatments and treatment responses are particular to
      children or differ from their adult equivalents. Also, many potentially useful
      treatments are unlicensed for children. In general practice, at least 1 in 10
      medicines prescribed forchildren are unlicensed or are used 'off-label'. These
      circumstances make the launch of the BNF for Children (BNFC) in September 2005 an
      important development. We review this new publication.

PMID- 16296664
TI  - Leukotriene receptor antagonists--an update.
AB  - Montelukast (Singulair-MSD) and zafirlukast (Accolate-AstraZeneca) are oral
      leukotriene receptor antagonists, licensed for the treatment of patients with
      asthma. In 1998, soon after their launch, we concluded that there was
      insufficient evidence to clearly define their place in treatment. Here, we
      reconsider their role in adults and children with asthma in the light of more
      recent evidence.

PMID- 16296665
TI  - Hip protectors.

PMID- 16296666
TI  - European Academy for Medicine of ageing: a new network for geriatricians in
      Europe.

PMID- 16296667
TI  - An inpatient bed for acute nursing home admissions.
AB  - BACKGROUND: Some older patients are admitted directly to nursing homes without a
      comprehensive assessment. OBJECTIVE: To determine whether a hospital assessment
      bed might provide better assessment, treatment and a more appropriate placement
      for selected older people. Setting a single bed in an elderly care unit of a
      district general hospital. SUBJECTS: Older people who general practitioners
      thought needed nursing home care but whose social workers felt might benefit from
      inpatient assessment. MAIN OUTCOME MEASURES: Type of treatment needed (acute
      care, rehabilitation, palliation, long-term care) and placement (home, nursing
      home, residential home or hospital). RESULTS: of 34 patients assessed, 22 (65%)
      needed further clinical assessment or care and 26 (75%) left hospital for places
      other than nursing homes. CONCLUSIONS: Inpatient assessment is a successful way
      of assessing the needs of some older people who would otherwise have been
      admitted directly from their homes to nursing homes.

PMID- 16296668
TI  - Can bedside assessment reliably exclude aspiration following acute stroke?
AB  - OBJECTIVE: To investigate the ability of a bedside swallowing assessment to
      reliably exclude aspiration following acute stroke. SUBJECTS: Consecutive
      patients admitted within 24 h of stroke onset to two hospitals. METHODS: A
      prospective study. Where possible, all patients had their ability to swallow
      assessed on the day of admission by both a doctor and a speech and language
      therapist using a standardized proforma. A videofluoroscopy examination was
      conducted within 3 days of admission. RESULTS: 94 patients underwent
      videofluoroscopy; 20 (21%) were seen to be aspirating, although this was not
      detected at the bedside in 10. In 18 (22%) of the patients the speech and
      language therapist considered the swallow to be unsafe. In the medical
      assessment, 39 patients (41%) had an unsafe swallow. Bedside assessment by a
      speech and language therapist gave a sensitivity of 47%, a specificity of 86%,
      positive predictive value (PPV) of 50% and a negative predictive value (NPV) of
      85% for the presence of aspiration. Multiple logistic regression was used to
      identify the optimum elements of the bedside assessments for predicting the
      presence of aspiration. A weak voluntary cough and any alteration in conscious
      level gave a sensitivity of 75%, specificity of 72%, PPV of 41% and NPV of 91%
      for aspiration. CONCLUSION: Bedside assessment of swallowing lacks the necessary
      sensitivity to be used as a screening instrument in acute stroke, but there are
      concerns about the use of videofluoroscopy as a gold standard. The relative
      importance of aspiration and bedside assessment in predicting complications and
      outcome needs to be studied.

PMID- 16296670
TI  - Estimating total Barthel scores from just three items: the European Stroke
      Database 'minimum dataset' for assessing functional status at discharge from
      hospital.
AB  - BACKGROUND: The European Stroke Database (ESDB) Project aims to develop a 'common
      clinical language' for stroke care by agreeing on terminology, definitions and
      clinical assessments. Each area of stroke assessment has a 'minimum dataset',
      which can be collected routinely and more detailed information can be added for
      particular studies. Measurement of patients' functional status at discharge is
      essential for assessing the impact of hospital care, but even simple activities
      of daily living scales like the Barthel index may not be easy to use routinely on
      busy acute units. We thus aimed to further simplify the 20-point Barthel index by
      reducing it to a few key items. METHODS: We initially analysed data on 169
      consecutive stroke patients discharged from one British hospital and found that a
      simple formula involving the combined subscores for urinary continence (Blad),
      bed-chair transfers C (Trans) and indoor mobility (Mob)-(Blad + Trans + Mob) x
      2.39 + 0.14-predicted the total BI score to within 1 point in 79% and to within 2
      points in 95% of cases. We then tested this three-item Barthel index (BI3) in
      four different stroke datasets (total n = 824). RESULTS: The predictions were
      accurate to +/-1 point in 72-81% and to +/-2 points in 88-97% of cases, and BI3
      accounted for 95% of the variance in total Barthel score. It was more accurate in
      patients without obvious mental impairment. CONCLUSIONS: For studies involving
      large groups of stroke patients, it is sufficient to know about each patient's
      continence, transfers and indoor mobility at discharge, in order to estimate the
      total Barthel score. These measures have therefore been incorporated, together
      with a simple observational measure of cognitive status, into the database
      minimum dataset for short-term functional outcome and are now being validated in
      international studies.

PMID- 16296669
TI  - Inter-rater reliability and validity of the action research arm test in stroke
      patients.
AB  - BACKGROUND AND PURPOSE: The Action Research arm test (ARAT) was constructed for
      assessing recovery of upper extremity function after cortical injury. The
      objective of the study was to verify the inter-rater reliability and validity of
      the ARAT in stroke patients. METHODS: 50 stroke patients participated in the
      study. For the purpose of inter-rater study, the ARAT was administered by three
      experienced raters on each patient within a 3-day period. Validity was assessed
      by comparing the patients' scores on the ARAT with those obtained for the other
      well-validated measurements evaluating upper extremity motor impairment and
      disability. RESULTS: Intra-class correlation coefficient (ICC) for the total
      score was 0.98 indicating very high inter-rater reliability. ICCs were also very
      high in each of the subscales. The score of the ARAT was closely correlated with
      that of the upper extremity part of the motor assessment scale, the arm sub-score
      of the motricity index and the upper extremity movements of the modified motor
      assessment chart (Pearson r = 0.96, 0.87 and 0.94, respectively). CONCLUSION: The
      preliminary results of this study support the value of the ARAT for measuring
      recovery of arm-hand function in stroke patients.

PMID- 16296671
TI  - Associations between malnutrition, poor general health and oral dryness in
      hospitalized elderly patients.
AB  - OBJECTIVE: To obtain information about the possible relationship between symptoms
      and signs of oral dryness and malnutrition/poor general health in hospitalized
      older people. DESIGN: A cross-sectional clinical investigation with measurements
      of unstimulated salivary flow rates (USFR), stimulated salivary flow rates
      (SSFR), nutritional status, serum albumin concentration and an evaluation of
      symptoms of oral dryness and loss of appetite by a questionnaire. SUBJECTS AND
      METHODS: A cohort of 99 elderly, non-psychiatric patients hospitalized for
      medical reasons; collection of demographic and health data from medical files,
      collection of USFR and SSFR, measurements of body mass index (BMI), lean body
      mass, fat body mass, serum album in concentration; completion of a questionnaire
      related to symptoms of oral dryness and the patients' appreciation of their
      nutritional status. MAIN OUTCOME MEASURES: SSFR and USFR. RESULTS: Mean age of
      the 99 patients was 82.5 +/- 4.0 years. Anthropometric examinations indicated
      malnutrition of severe or intermediate degree in about 50% while 46% showed
      moderately and 40% severely reduced albumin. Loss of appetite was present in 54%
      and 51% complained of oral dryness; 17% had an USFR <0.1 ml/min and 26% a SSFR
      <0.5 ml/min. Significant associations were found between (i) reduced salivary
      flow rate, malnutrition and reduced serum albumin concentration, (ii) recent loss
      of appetite and low serum album in concentration and (iii)complaints of oral
      dryness and reduced salivary flow rates. There were also significant associations
      between complaints of oral dryness, loss of appetite and low BMI. CONCLUSION:
      Reduced salivary secretion and complaints of oral dryness could be signs of poor
      nutritional or general health status of elderly patients. Reduced salivary
      secretion and feeling of oral dryness could have a negative effect on
      alimentation, appetite and oral comfort.

PMID- 16296672
TI  - Variations by age in symptoms and dependency levels experienced by people in the
      last year of life, as reported by surviving family, friends and officials.
AB  - OBJECTIVE: To explore the relationships between age, reported symptoms and
      dependency in the last year of life in those dying from cancer and in those dying
      from other causes. DESIGN: Secondary analysis of data from the Regional Study of
      Care for the Dying, a retrospective interview survey of deaths in 1990 in 20
      nationally representative English health districts. There were 2061 cancer deaths
      and 1469 non-cancer deaths (sudden deaths were excluded). MAIN RESULTS: In cancer
      patients, the mean number of symptoms reported to have been experienced in the
      last year of life decreased with age (from 8.29 in those aged <65 to 7.79 in
      those aged 65 -74, 7.37 in those aged 75-84 and 7.42 in those aged 85 and older),
      while the number of symptoms reported to have lasted more than 6 months increased
      (2.93, 3.15, 3.24 and 3.52). In both cancer and non-cancer patients the
      proportion of symptoms reported to have been 'very distressing' decreased with
      age (cancer, 45, 43, 40 and 35%; non-cancer, 39, 38, 34 and 27%). In non-cancer
      patients the mean number of self-care tasks the deceased had needed help with
      increased substantially with age (2.23, 2.50, 3.04 and 3.95); in cancer patients
      the mean level was higher and there was no age gradient (3.89, 3.94, 3.83 and
      4.1). The prevalence of dependency on most of the seven self-care tasks in cancer
      patients was comparable with or higher than that in the older and most restricted
      non-cancer patients. CONCLUSION: Younger cancer patients are more likely than
      older cancer patients to need help with relieving distressing symptoms. However,
      some elderly patients were reported to have had very distressing symptoms, and
      these patients should not be excluded from specialist palliative care services on
      the basis of their age. Cancer patients did not show increased dependency with
      age, indicating the importance of community health and social services being
      appropriate for and accessible by cancer patients of all ages.

PMID- 16296673
TI  - A kinematic comparison between elderly and young subjects standing up from and
      sitting down in a chair.
AB  - BACKGROUND AND AIMS: The transfer from sitting to standing and back to sitting as
      the two phases of the same task has never been studied in elderly people. The
      purposes of this study were to analyse and compare kinematic features of the
      whole task (standing up and sitting down) and to determine whether there are age
      related differences upon movement kinematics in healthy elderly persons during
      the whole sequence (standing up and sitting down). METHODS: The movements of
      various parts of the body were measured with a 100 Hz television image analyser
      that computed the co-ordinates of small reflective markers glued onto the skin of
      the subjects. The task was conducted using an armless chair set to 100% of knee
      height under four conditions: at normal speed in light, at normal speed in the
      dark, at fast speed in light and at fast speed in the dark. TYPE OF STUDY:
      Laboratory study. RESULTS: In young subjects, the task was characterized by
      similar acromion trajectories and angular displacement of trunk in standing up
      and sitting down and by a stabilization of the head in space during the two
      phases. However, the time required to achieve the movement was found to be
      greater in sitting down than in standing up, and an adjustment of velocity
      appeared in final part of the movement before reaching the chair. In sitting
      down, as in carrying out a pointing task of upper limb, an adjustment was
      required to achieve accuracy. This feature was not found in standing up. Age
      related differences appeared to be more important during sitting down than during
      standing up. Moreover, deterioration of head stability was found in elderly
      subjects, particularly when the task was achieved rapidly and in darkness.
      CONCLUSION: There is a relationship between changes in the motor control of the
      task, which appeared during periods of potential postural instability, and the
      effects of ageing on postural stability.

PMID- 16296674
TI  - Age-related variability in body composition methods for assessment of percent fat
      and fat-free mass in men aged 20-74 years.
AB  - INTRODUCTION: Assessing body composition is important because of the association
      between excess body fat or obesity and the increased risk for coronary artery
      disease, diabetes, hyperlipidaemia and hypertension. Methodological differences
      among indirect body composition techniques are a source of variability that can
      affect estimations of fat-free mass (FEM) or percent fat, especially for
      different age groups. PURPOSE: This study examined the effect of age on the
      estimation of body composition by three methods based on the two-component model.
      One hundred and fifty-three men were placed into 5-year age groups from 20-24 to
      70-74 years. Body composition was assessed by hydrodensitometry (underwater
      weighing; 40K spectroscopy (K40) and anthropometry. RESULTS: Day-to-day
      reliability was excellent for each method. Correlation coefficients between
      methods, independent of age, ranged from r= 0.71 (K40 and UWW) to r = 0.83 (UWW
      and anthropometry) for% fat and from r = 0.76 (K40 and anthropometry) to r = 0.90
      (UWW and anthropometry) for FFM. Correlations between techniques weakened and
      showed greater variability as age increased. UWW produced the highest % fat and
      lowest FFM for the different age groups, while K40 and anthropometry yielded
      similar body composition values. All three methods detected age-related
      differences in % fat; however, only UWW determined a significant age effect in
      FFM. The greatest discrepancies between the methods occurred for the oldest age
      groups (60-74 years), but noticeable differences began occurring after the age of
      40. CONCLUSIONS: Each method produced reliable data. Care should be taken when
      choosing any method based on the two-component model, especially when different
      age groups are being examined, since estimating % fat and FFM is dependent on the
      age-related chemical composition of an individual and the limitations of each
      method.

PMID- 16296675
TI  - Depression in elderly outpatients with disabling chronic obstructive pulmonary
      disease.
AB  - INTRODUCTION: Depression is common in both young adults and elderly people with
      chronic obstructive pulmonary disease (COPD). METHODS: We compared the prevalence
      of depressive symptomatology in elderly outpatients with stable disabling COPD
      with that in healthy controls and age-matched patients with other disabilities,
      and also assessed the relation between degree of disability, quality of life and
      depressive symptoms. The subjects were 96 older people with COPD [56 men; aged 70
      93 (mean 78) years], 55 normal controls [23 men; aged 70-90 (mean 78) years] and
      53 disabled controls [27 men; aged 70-92 (mean 78) years]. Exclusion criteria
      were acute respiratory exacerbation or use of oral steroids in the last 6 weeks,
      known previous psychiatric disorder and acute or chronic confusion. RESULTS: Mean
      (and SD) values for 1-s forced expiratory volume (FEV1) were 51 (20) % in COPD
      subjects, 107 (24) % in normal controls and 82 (13)% in disabled controls. Forty
      four subjects with COPD (46%), six normal controls (11%) and 14 disabled controls
      (26%) scored in the 'caseness' range for depressive ideation on the Brief
      Assessment Schedule Depression Cards (BASDEC) screening questionnaire. A multiple
      regression analysis was performed for the COPD group to identify factors
      predictive of BASDEC score. Predictive variables were total quality of life score
      [P<0.0001], Chronic Respiratory Questionnaire and level of activities of daily
      living (Nottingham extended activities of daily living scale) [P = 0.001].
      Spirometry results and exercise tolerance (6-min walk distance) did not help
      predict BASDEC score (R2 = 0.50). CONCLUSIONS: Depressive symptoms are common in
      elderly patients with COPD; prevalence and/or severity of depressive symptoms may
      be greater in those who are most disabled.

PMID- 16296676
TI  - Methodology, results and quality of clinical trials of tacrine in the treatment
      of Alzheimer's disease: a systematic review of the literature.
AB  - OBJECTIVE: To review systematically the methodology, results and quality of
      clinical trials of tacrine in the treatment of Alzheimer's disease (AD). METHODS:
      Trials included were those conducted on AD patients, aged 40 years or over,
      assigned to tacrine- or placebo-based treatment. Studies were identified via the
      Cochrane Collaboration and MEDLINE databases. Trial-selection and data-extraction
      were carried out separately by two reviewers working independently. Any
      differences of opinion that arose were resolved by discussion. RESULTS: We
      identified 49 trials published in the period 1 January 1981 - 1 May 1997. Of
      these, 21 were randomized controlled trials, eight parallel-group and 13 cross
      over type. In the random trials, tacrine dosage ranged from 25 to 200 mg/day,
      with a duration of 3-36 weeks. In all, 3555 patients with mild to moderate AD
      started treatment and 1149 failed to complete the course (mean 33.4% patients per
      trial). Over 80% of patient withdrawals were tacrine-related. Adverse events
      affected a mean of 59% patients per trial (range 34-90%), mainly in the form of
      cholinergic manifestations (mean 30.2%, range 5-62%) and transaminase elevations
      (mean 28.6%, range 0-53%). Adverse events were more frequent at doses of > or =
      100 mg/day and disappeared on discontinuation of tacrine treatment. Just over 20%
      of patients given tacrine experienced improvements in cognitive function (3-4
      points in Alzheimer's Disease Assessment Scale cognitive subscale and 2-3 points
      in Mini-Mental State Examination) and in functional ability at 3-6 months of
      treatment. No study gave a description of concealment of the randomization
      sequence or the success of the double-blind procedure. CONCLUSIONS: Tacrine shows
      a modest degree of efficacy among a small proportion of patients with mild to
      moderate AD, yet has important adverse effects which limit its clinical
      usefulness. It is not known which AD patient subgroup could benefit from the
      treatment. Information on the long-term effects of tacrine (over periods
      exceeding 7 months) and its effects on quality of life, patient
      institutionalization and mortality and patient burden on caregivers is
      inadequate.

PMID- 16296677
TI  - Previous psychiatric history as a risk factor for late-life dementia: a
      population-based case-control study.
AB  - OBJECTIVE: To test the hypothesis that risk for dementia in late life is
      increased by a history of earlier psychiatric illness, and to examine the
      specificity of any such association. METHODS: Frequency of earlier treated
      psychiatric illness was established by record searches and informant histories
      for all persons aged over 60 who were entered on the Camberwell dementia case
      register over a 2-year period and for an individually matched control group of
      the local elderly population, drawn from the files of the area Family Health
      Services Authority. RESULTS: Of 559 persons with a clinical diagnosis of
      dementia, 70 (12.5%) had a history of psychiatric illness long preceding, and
      apparently unrelated to, the onset of dementia. When these patients were compared
      with a matched comparison group of dementia register patients who had no recorded
      psychiatric history, the two groups appeared broadly similar in type of dementia,
      severity and clinical features. Sixty-three of the earlier psychiatric histories
      could be identified from the available medical records alone. Applying the same
      procedure to the matched control group of Camberwell residents yielded from the
      559 only 19 (3.4%) with a history of treated psychiatric illness before the age
      of 70. The difference in case frequency between the two groups was highly
      significant and corresponded to an estimated odds ratio of 3.6. The increase in
      risk, which was not restricted to dementia of Alzheimer type, appeared to be
      characteristic of major psychiatric illness, rather than specific for depression.
      CONCLUSION: There is a positive association between previous psychiatric history
      and late-life dementia which is of predictive significance. The underlying causal
      links merit further research.

PMID- 16296679
TI  - Will elderly rest home residents wear hip protectors?
AB  - BACKGROUND: Hip fracture is a common cause of morbidity and mortality in elderly
      people, for whom osteoporosis, the risk of falling and direct trauma to the hip
      during the fall are the major risk factors. External hip protectors have been
      developed which reduce the risk of hip fracture after a fall. However, compliance
      with their use is uncertain. We addressed this issue in a sample of elderly
      Dorset rest home residents over a 3-month period. METHODS: 31 rest homes agreed
      to participate. Of the 288 female subjects approached, 141 gave their informed
      consent and 101 were allocated to the intervention arm of the study. Their ages
      ranged from 64 to 98 years, and 44% reported a fall during the preceding 12
      months. Each subject was fitted with three pairs of protector pads (Sahvatex,
      Denmark) sewn into specially designed undergarments. Randomly timed fortnightly
      visits were made to each subject to assess compliance for 12 weeks. FINDINGS: 27
      subjects were compliant for the whole study period; 54 wore the protector pads
      for less than a week, largely for reasons of poor fitting or discomfort; the
      remainder withdrew at varying intervals between 1 and 12 weeks. During the study
      period, there were nine recorded falls onto the hip, six of which occurred in
      women wearing protectors. None resulted in hip fracture. CONCLUSION:
      Approximately 50% of elderly rest home residents who are mentally able would wear
      hip protectors in order to prevent hip fractures. Long-term compliance drops to
      about 30%. Compliance could be increased substantially if the pads and
      undergarments were modified to enhance their fit and to reduce the discomfort
      associated with their use.

PMID- 16296678
TI  - Placement of dementia sufferers in residential and nursing home care.
AB  - BACKGROUND: Few UK studies have examined the associations of residential or
      nursing home placement in dementia sufferers. METHOD: 124 patients with mild to
      moderate dementia (according to the Diagnostic and Statistical Manual of Mental
      Disorders, third edition, revised) and in contact with clinical services were
      evaluated with a detailed standardized assessment and followed-up at monthly
      intervals for 1 year. RESULTS: 25 (21.6%) of the 116 patients living at home were
      admitted to residential or nursing home care during the follow-up year.
      Institutional placement was associated with greater severity of cognitive
      impairment, severity of parkinsonism and the failure of carers to adopt active
      coping strategies. CONCLUSION: An intervention to improve coping skills in carers
      may decrease the rates of residential and nursing home placement.

PMID- 16296680
TI  - Home from home: residents' opinions of nursing homes and long-stay wards.
AB  - OBJECTIVE: To compare the levels of satisfaction expressed by residents of
      nursing homes with those of patients in geriatric long-stay wards. DESIGN: A
      structured satisfaction questionnaire containing 37 closed and two open questions
      was used to elicit responses from residents of nursing homes in the former South
      West Thames Regional Health Authority area. This was compared with a similar
      survey using the same questionnaire among patients in geriatric long-stay wards
      surveyed in 1989. SETTING: respondents came from a sample of nursing homes chosen
      to be representative of both size and geographical location. Nursing homes were
      stratified by number of beds (1-19, 20-29, 30+) and clustered by location (to
      reflect the urban, semi-rural and coastal nature of the region). SUBJECTS: A
      random sample was drawn from each grouping (size and location) to yield a
      resident sample of 850 in 36 nursing homes. This figure was similar to the number
      of patients (808) in geriatric long-staywards surveyed in 1989. All eligible
      nursing home patients were assessed for physical dependency. Mental confusion was
      ascertained by the Abbreviated Mental Test Score (AMTS). Patients who scored
      three or less on the AMTS (indicative of severe confusion) or had dysphasia,
      profound deafness or concurrent serious illness were excluded from further study.
      RESULTS: 377 nursing home residents were able to complete the questionnaire and
      their answers were compared with those of 291 long-stay geriatric patients. The
      responses to the five themes--relations with staff, autonomy, amenities, privacy
      and social environment-show some minor differences between the two groups but
      what is more noticeable is the similarity of their views. This is important as
      much social policy assumes that the more 'homely' atmosphere of the nursing home
      should elicit higher levels of satisfaction than the 'institutional' setting of
      the hospital ward. CONCLUSION: We conclude that the difference between nursing
      homes and hospital wards in terms of their institutionalizing capacities is not
      as profound as policy-makers believe.

PMID- 16296681
TI  - Quality of life and longevity: a study of centenarians.
AB  - OBJECTIVE: Interest in centenarians has focused on two particular aspects: the
      antecedents of extreme old age and the psychophysical well-being of the very old.
      Our study deals with the latter aspect and aims to assess the quality of life of
      Italian centenarians. METHOD: Using data collected using two questionnaires
      designed to investigate quality of life in elderly people, three groups of 38
      elderly subjects were compared: centenarians and subjects aged between 75 and 85
      years and 86 and 99 years. RESULTS: The centenarians complained less
      spontaneously about their health (maintained in part by medical treatments), but
      declared having greater functional disability. Their cognitive function appears
      to be reasonably well preserved and they have lower scores for anxiety and
      depression than the subjects in the two younger groups. They consider themselves
      religious, satisfied with their financial situation but no longer interested in
      sex or involved in recreational activities. They report greater satisfaction with
      life and with social and family relations than do less elderly individuals.
      CONCLUSIONS: The centenarians we interviewed seem to be well adapted to their
      lives and to maintain a more positive attitude than the subjects in the two
      younger groups.

PMID- 16296682
TI  - The viability of soft tissues in elderly subjects undergoing hip surgery.
AB  - AIMS: To assess the viability of soft tissues in elderly patients subjected to
      prolonged support pressures. DESIGN: measurements were performed on the soft
      tissues of patients undergoing surgery for fracture of the proximal femur.
      METHODS: 10 subjects, mean age 84 years, participated. Transcutaneous gas
      tensions were continuously monitored in an area adjacent to the contralateral
      greater trochanter, which was loaded with an external applicator. Subcutaneous
      interstitial pressures using a slit catheter were also measured. RESULTS:
      Transcutaneous oxygen partial pressure fell in some patients to critically low
      levels, defined as below 2.7 kPa (20 mmHg), whilst they were subjected to normal
      interface pressures on the operating table. Transcutaneous partial carbon dioxide
      pressures rarely rose above 8.0 kPa (60 mmHg). The measured interstitial
      pressures could lead to local occlusion of skin microvessels. CONCLUSIONS: This
      study confirms that tissue viability could be compromised in elderly patients
      undergoing surgical procedures. The methods employed may be of value in assessing
      support surfaces in the operating theatre to reduce the incidence of pressure
      sores in this high-risk patient group.

PMID- 16296684
TI  - Acceptability and compliance with wearing energy-shunting hip protectors: a 6
      month prospective follow-up in a Finnish nursing home.
AB  - OBJECTIVES: To assess the acceptability and compliance with use of an energy
      shunting hip protector in institutionalized elderly people. DESIGN AND SETTING: A
      6 month prospective follow-up in a Finnish nursing home. PARTICIPANTS: 19
      ambulatory nursing home residents with a high risk of hip fracture. MAIN OUTCOME
      MEASURES: The proportion of the residents who were willing to use the device, the
      number of hours of wearing the protector and the attitudes of the study subjects
      and the caregivers towards the appearance, comfort, fit, efficacy and laundering
      of the protector. RESULTS: 12 of the 19 ambulatory residents (63%) agreed to use
      the protector. During the study period, these subjects wore the protector on
      average for more than 90% of their active days, i.e. the days they were mobile.
      Two subjects wore the protectors at night time; the rest only during waking
      hours. Mean wearing time during waking hours exceeded 90%. CONCLUSION: External
      hip joint protectors are a feasible strategy to prevent hip fractures in
      institutionalized elderly people. The attitude, education and motivation of the
      staff may be a factor in achieving good user compliance. Further community-based
      studies on acceptability and compliance in wearing external hip joint protectors
      are needed for verification of benefits to the general population of older
      people.

PMID- 16296683
TI  - Prolonged digitoxin half-life in very elderly patients.
AB  - The digitoxin half-life in elderly patients in the eight and ninth decade was
      more prolonged (mean +/- SD: 25 +/- 9 days) than in younger people (6.7 +/- 1.7).
      These elderly patients accumulated digitoxin even on a dose of 0.05 mg/ day. The
      symptoms of digitoxin intoxication disappeared on discontinuation of medication.
      When digitoxin is used in the treatment for heart failure in the very elderly
      patients, one should be aware of the possibility of digitoxin intoxication, even
      on a low dose.

PMID- 16296685
TI  - Assessment of femoral bone fragility and fracture risk by ultrasonic measurements
      at the calcaneus.
AB  - BACKGROUND: Quantitative ultrasound measurement (broadband ultrasound attenuation
      and speed of sound) is emerging as an alternative to photon absorptiometry
      techniques in the assessment of osteoporosis. OBJECTIVE: To discuss briefly the
      fundamentals of ultrasound measurement of bone and critically review recent
      studies on the role of ultrasound in bone quality assessment and hip fracture
      prediction. CONCLUSIONS: The relationships between ultrasound and bone mineral
      density are too weak to allow accurate prediction of bone density at any skeletal
      site--including the hip--from an ultrasound measurement at the calcaneus.
      However, in vitro evidence indicates that ultrasound provides structural
      information in addition to density. In line with these in vitro data, recent
      prospective studies have shown that ultrasound predicts hip fractures strongly
      and independently of densitometry in older women.

PMID- 16296686
TI  - Management of spasticity.

PMID- 16296687
TI  - Research into the treatment of vascular dementia in China using traditional
      therapies.

PMID- 16296688
TI  - Hypophysial insufficiency in old age: a forgotten syndrome?

PMID- 16296689
TI  - Social support and activities of daily living in older Afro-Caribbean and white
      UK residents.

PMID- 16296690
TI  - Improving the care of elderly diabetic patients.

PMID- 16296691
TI  - Complications of laparoscopic cholecystectomy.

PMID- 16296692
TI  - What degree of medical treatment do nursing home residents want in case of life
      threatening disease?

PMID- 16296694
TI  - Not in my water supply.

PMID- 16296693
TI  - Target: trans fats.

PMID- 16296695
TI  - 24-hour protection and control: a new era of calcium antagonists. Proceedings of
      a satellite symposium, Cannes, France, September 15, 1989.

PMID- 16296696
TI  - 24-hour blood pressure monitoring in hypertension.
AB  - It has been recognized for some time that blood pressure is highly variable over
      a 24-h period. A number of studies have demonstrated that the extent and severity
      of target-organ damage associated with hypertension can be correlated more
      closely with blood pressure values monitored continuously for 24 h than with
      individual values recorded sphygmomanometrically. A great deal of interest is
      focused on whether absolute values of diastolic or systolic blood pressure,
      values during the day or night, or the rate of change of blood pressure such as
      the rapid increase that occurs in the early morning are more or less important
      factors contributing to the mortality and morbidity associated with hypertension.
      Work from our own unit provides evidence of the importance of two features in the
      variability of blood pressure. Blood pressure decreases during the night, but
      remains higher in hypertensive patients than in normotensive subjects. The mean
      nighttime blood pressure was shown to correlate with hypertension-related target
      organ damage almost as closely as the mean daytime blood pressure. Using 24-h
      blood pressure monitoring, we have shown that the higher the mean 24-h blood
      pressure, the greater the extent and severity of target-organ involvement. In
      addition, for patients with comparable mean 24-h blood pressure values, larger
      degrees of blood pressure variability throughout the monitoring period were
      associated with more target-organ damage. Taking the available evidence into
      account, it is probably important that treatments used for hypertension should
      provide control of blood pressure for a full 24-h period confirmed by ambulatory
      blood pressure monitoring.

PMID- 16296697
TI  - Amlodipine: pharmacokinetic profile of a low-clearance calcium antagonist.
AB  - Structural features of amlodipine give the molecule physicochemical and
      pharmacokinetic properties that are unique among calcium antagonists. Amlodipine
      is absorbed gradually after oral administration (peak plasma levels 6-12 h
      postdose) and has an absolute bioavailability of 64%. Low clearance and a high
      volume of distribution give amlodipine a long elimination half-life, and mean
      effective plasma levels are maintained with once-daily doses. With repeated once
      daily dosing, the steady state is achieved after the seventh to ninth dose. The
      pharmacokinetic properties of amlodipine avoid the sharp fluctuations in plasma
      level seen with other calcium antagonists that are associated with vasodilatation
      induced side effects such as tachycardia, headache, and flushing. The
      pharmacokinetics of amlodipine are not significantly altered in elderly or
      renally impaired patients, but there is reduced clearance in patients with
      hepatic impairment. There are no pharmacokinetic interactions between amlodipine
      and cimetidine or digoxin.

PMID- 16296698
TI  - 24-hour blood pressure control with the once-daily calcium antagonist amlodipine.
AB  - The efficacy and toleration of once-daily amlodipine (5-10 mg) was studied in 11
      patients with mild to moderate hypertension. Continuous intra-arterial blood
      pressure monitoring was used to study the effects of amlodipine over a 24-h
      period. Following a 2-week placebo run-in period, amlodipine was given initially
      as a single-blind 5-mg dose for 2 weeks and increased to 10 mg if required to
      control blood pressure for a further 4 weeks. Twenty-four-hour intra-arterial
      blood pressure recordings made after 6 weeks of treatment with amlodipine
      revealed that amlodipine effectively reduced blood pressure throughout the whole
      24-h period without altering the normal circadian pattern. The mean daytime blood
      pressure was reduced from 165/103 to 147/89 mm Hg (p < 0.05) and the mean
      nighttime blood pressure was reduced from 137/79 to 121/69 mm Hg (p < 0.05).
      There was no significant change in heart rate. The mean supine blood pressure
      measured sphygmomanometrically was reduced from 169/103 mm Hg after placebo to
      153/98 mm Hg after 2 weeks of treatment and to 145/92 mm Hg at the end of the
      study. The results of isometric and dynamic exercise testing showed that
      amlodipine decreased blood pressure, with no postural decrease on tilting and no
      change in the proportional increase in blood pressure at peak exercise.
      Amlodipine was well tolerated although one patient developed ankle edema that
      would have required discontinuation had she not already completed the study. This
      study has shown that amlodipine effectively reduced blood pressure for 24 h after
      once-daily dosing and was well tolerated.

PMID- 16296699
TI  - Effect of amlodipine on 24-hour ambulatory blood pressure in hypertensive
      patients.
AB  - Sixteen hypertensive patients (diastolic blood pressure of 95-114 mm Hg) were
      randomized to receive 5 mg of amlodipine daily or placebo, double blind, for 4
      weeks. Antihypertensive efficacy was assessed using ambulatory blood pressure
      monitoring at baseline and following double-blind therapy in conjunction with
      sphygmomanometric measurement at 2-week intervals. Laboratory tests, ECG, and
      adverse effects were recorded to assess tolerability. Amlodipine treatment
      significantly reduced ambulatory blood pressure without altering the normal
      circadian variation throughout the monitoring period. Supine and standing blood
      pressure were significantly reduced by amlodipine 24 h postdose. Amlodipine was
      well tolerated and was not associated with reflex tachycardia.

PMID- 16296700
TI  - A double-blind comparison of amlodipine and placebo added to open enalapril in
      patients with moderate to severe essential hypertension.
AB  - The antihypertensive efficacy and tolerability of amlodipine in combination with
      enalapril were assessed in this two-center study. Patients with moderate to
      severe hypertension and with diastolic blood pressure > 95 mm Hg after 4 weeks of
      treatment with open-label enalapril 5-10 mg daily were randomized to receive
      amlodipine 10 mg daily or placebo, double-blind for a further 4 weeks, in
      combination with open-label enalapril. There were significantly larger falls in
      mean supine and standing blood pressure in patients treated with enalapril plus
      amlodipine than in those treated with enalapril plus placebo. There was no
      clinically or statistically significant difference between treatment groups in
      pulse rate, ECG, or body weight. Side effects were generally mild or moderate
      with a similar incidence in both treatment groups. The study showed once-daily
      amlodipine to be effective and well tolerated when administered as add-on therapy
      to enalapril.

PMID- 16296701
TI  - A double-blind, parallel, comparative evaluation of amlodipine vs. captopril in
      the monotherapeutic treatment of mild and moderate essential hypertension.
AB  - A double-blind, parallel, comparative study of the antihypertensive efficacy and
      safety of once-daily oral doses of amlodipine (5-10 mg/day) vs. twice-daily oral
      doses of captopril (25-50 mg twice daily) in adult patients with mild or moderate
      essential hypertension (supine diastolic blood pressure of 95-115 mm Hg) was
      undertaken in two hospital centers. Interim analysis of data from 40 patients
      shows that amlodipine and captopril both significantly (p < 0.05) reduced blood
      pressure compared with baseline. Nineteen of 21 (90.5%) amlodipine-treated
      patients and 15 of 19 (78.9%) captopril-treated patients had their diastolic
      blood pressure "normalized" (< 90 mm Hg) with mean final doses of 8.2 and 76.7
      mg/day, respectively. At the final visit, there were no statistically significant
      differences between the two treatment groups in either mean supine or standing
      blood pressure. Minor nonsignificant changes in standing heart rate were observed
      in both treatment groups. Seven of the 21 amlodipine-treated patients and 3 of
      the 19 captopril-treated patients reported adverse experiences. No patients in
      either treatment group discontinued due to adverse events; one patient in the
      amlodipine group required a dose reduction. These interim data indicate that the
      overall efficacy and safety profiles of these two drugs are comparable.

PMID- 16296703
TI  - Amlodipine in hypertension: its effects on platelet aggregation and dynamic
      exercise.
AB  - The antihypertensive efficacy and safety of once-daily amlodipine (5-10 mg) were
      studied in patients with essential hypertension. The study also included an
      assessment of the effects of single doses of amlodipine on platelet aggregation.
      Ten patients received amlodipine (mean daily dose of 7 mg) for 12 weeks in an
      open chronic study preceded by a 4-week placebo run-in period. Amlodipine
      significantly reduced the mean dorsal supine (-31/-20 mm Hg), sitting (-34/-23 mm
      Hg), standing (-34/ -23 mm Hg), and postexercise (-30/-20 mm Hg) blood pressures
      (BPs) at the end of 12 weeks of treatment compared with the placebo run-in period
      (p < 0.005), with no significant change in heart rate. At the end of a 4-week
      placebo washout phase following the chronic study, nine of the patients received
      an acute single 10-mg dose of amlodipine. Exercise testing before and 6 h after
      dosing showed that an acute 10 mg dose of amlodipine reduced BP without modifying
      the physiologic response to dynamic exercise. Amlodipine significantly reduced
      the degree of platelet aggregation in these patients (p < 0.005) induced by
      either collagen or ADP. This study demonstrated that amlodipine once daily was an
      effective antihypertensive agent and significantly inhibited platelet
      aggregation.

PMID- 16296702
TI  - An open, parallel, comparative evaluation of amlodipine and nitrendipine in the
      monotherapeutic treatment of mild and moderate essential hypertension.
AB  - The efficacy and safety of the dihydropyridine calcium antagonists amlodipine and
      nitrendipine as single-agent therapy of mild to moderate hypertension were
      compared in an open, parallel-group study. Interim analysis of data from 74
      patients (43 male, 31 female) from an expected final total of 96 patients is
      reported. Amlodipine normalized blood pressure (< or = 90 mm Hg) in 94.7% of
      patients with a mean final dose of 8.3 mg/day, compared with normalization of
      blood pressure in 83.3% of patients treated with nitrendipine with a mean final
      dose of 28.3 mg/day. Only nitrendipine produced a statistically significant
      increase in heart rate after 2 and 4 weeks of therapy. Nitrendipine-treated
      patients reported more adverse events (47.2%) than the amlodipine-treated group
      (26.3%). Two patients from the nitrendipine group discontinued treatment due to
      treatment-related adverse events and one patient required a dose reduction. In
      the amlodipine-treated group, all adverse events were mild to moderate and dose
      reduction was required in one patient. In conclusion, although amlodipine and
      nitrendipine have comparable antihypertensive efficacy, in this study amlodipine
      was associated with fewer adverse effects.

PMID- 16296704
TI  - Open evaluation of amlodipine in the monotherapeutic treatment of systolic
      hypertension in the elderly.
AB  - The antihypertensive efficacy and safety of amlodipine (5-10 mg once daily for 10
      weeks) was assessed in elderly patients with primary systolic hypertension
      (average sitting and standing systolic blood pressure > or = 160 mm Hg and
      diastolic blood pressure < or = 95 mm Hg). Interim analysis of data from 25
      patients shows that amlodipine treatment produced significant decreases in
      sitting blood pressure (-26.8/-11.4 mm Hg; p < 0.05). Efficacy assessments after
      8 weeks of therapy showed 15 of 21 (71.4%) evaluable patients were considered
      therapeutic successes with amlodipine (defined as a fall from baseline in sitting
      systolic blood pressure of > or = 20 mm Hg or to < or = 150 mm Hg with a fall of
      > or = 10 mm Hg). Of the six evaluable patients who were not considered
      therapeutic successes using this definition, three had clinically beneficial
      falls in systolic blood pressure of 16-18 mm Hg. Fourteen patients were
      considered therapy successes on the basis of assessments taken 48 h postdose at
      the end of the study. Investigators' overall impression of efficacy was excellent
      or good in 21 patients (84%). Amlodipine treatment had no significant effect on
      heart rate. Amlodipine was generally well tolerated, with no patients being
      withdrawn due to side effects. Investigators' evaluation of toleration was
      excellent or good in 22 patients (88%).

PMID- 16296705
TI  - The efficacy and safety of amlodipine in the treatment of mild and moderate
      essential hypertension in general practice.
AB  - The antihypertensive efficacy and safety of amlodipine was evaluated in an open,
      multicenter general practice study. Hypertensive patients with sitting diastolic
      blood pressure in the range 95-115 mm Hg entered an initial 2-week baseline
      period during which they received placebo in a single-blind fashion. The dose of
      any concomitant antihypertensive treatment was kept constant for 4 weeks prior to
      baseline evaluations and throughout the study. Patients with an average sitting
      diastolic blood pressure > or = 95 mm Hg and < or = 115 mm Hg at two consecutive
      visits during the baseline period continued to the 8-week dose adjustment phase
      of the study. Patients were started on 5 mg of amlodipine once daily adjusted
      after 4 weeks to 10 mg once daily to achieve a target sitting diastolic blood
      pressure < or = 90 mm Hg. Amlodipine treatment produced significant falls in
      blood pressure (-23.7/-17.3 mm Hg; p < 0.05) with no effect on heart rate.
      Amlodipine was well tolerated, with most adverse events being mild or moderate.
      Investigators' global evaluation of toleration was excellent or good in 92% of
      patients. Subgroup analysis showed amlodipine to be equally efficacious and well
      tolerated in elderly or young patients, and in patients taking amlodipine as
      monotherapy or combination therapy.

PMID- 16296706
TI  - Cardioprotective effects of amlodipine in animal models of ischemia and
      reperfusion.
AB  - The protective effect of amlodipine was studied in isolated blood-perfused cat
      hearts made globally ischemic for 60 min followed by reperfusion for 60 min.
      Ischemia-induced alterations of left ventricular developed pressure and
      compliance were monitored. Amlodipine produced significant decreases in
      myocardial oxygen consumption (6.2 +/- 0.4 to 4.4 +/- 0.4 ml of oxygen/min/100 g)
      and coronary vascular resistance, as assessed by changes in perfusion pressure
      (120 +/- 1 to 100 +/- 4 mm Hg). When administered before the onset of global
      ischemia, amlodipine decreased the development of ischemic contracture as
      reflected by a progressive increase in resting left ventricular diastolic
      pressure. The return of contractile function, 60 min after reperfusion, was
      improved significantly in amlodipine-treated hearts compared to controls and
      there was better maintenance of the tissue concentration of Na+, Ca2+, and K+. In
      a canine model of regional myocardial ischemia (6 h) followed by reperfusion,
      amlodipine at 150 microg/kg, administered 15 min before reperfusion (90 min),
      reduced infarct size expressed as a percentage of the area at risk (34.5 +/- 3.8%
      vs. 45.9 +/- 2.8%, p = 0.027). We conclude that amlodipine reduces myocardial
      ischemic injury by mechanism(s) that may involve a reduction in myocardial oxygen
      demand as well as by positively influencing transmembrane Ca2+ fluxes during
      ischemia and reperfusion.

PMID- 16296707
TI  - The calcium antagonists in vasospastic angina.
AB  - Coronary vasospasm is an important pathophysiologic mechanism of angina at rest.
      Because the calcium antagonists are potent vasodilators, they have become widely
      used and are now considered the treatment of choice for vasospastic angina.
      Practically all currently available calcium antagonists in the United States have
      been shown to be efficacious and safe for the therapy of vasospastic angina.
      However, because spontaneous remissions are common and angina attacks can
      frequently occur during the nighttime, considerations such as the duration of
      action of a given agent, the duration of treatment, and patient compliance have
      become important in the selection of the most appropriate therapy. Amlodipine is
      a long-acting dihydropyridine derivative that is suitable for use as a once-daily
      calcium antagonist. There is preliminary evidence that amlodipine is efficacious
      and well tolerated in vasospastic angina. Amlodipine, therefore, has the
      potential to become the preferred calcium antagonist for this condition.

PMID- 16296708
TI  - The circadian rhythm of angina pectoris.
AB  - Analysis of diary card data from 33,999 angina attacks recorded in 1,022 patients
      with chronic stable angina showed a clear circadian pattern to the frequency of
      angina that resembles patterns previously described for myocardial infarction and
      sudden cardiac death, with a peak in the morning. The majority of angina attacks
      were preceded by physical exertion and the circadian pattern was more pronounced
      for exertional angina than nonexertional angina. In this study, treatment with
      beta-blockers did not prevent the morning peak of angina attacks.

PMID- 16296709
TI  - A double-blind, placebo-controlled, parallel dose-response study of amlodipine in
      stable exertional angina pectoris.
AB  - A placebo-controlled, double-blind, dose-response study of amlodipine (1.25, 2.5,
      5, and 10 mg once daily) was carried out in 136 patients with stable exertional
      angina pectoris. Improvements in total exercise tolerance, time to onset of
      angina during exercise, ST-segment deviation at maximum common load, frequency of
      angina attacks, and nitroglycerin consumption were greater following amlodipine
      than placebo. The maximum improvement in exercise parameters occurred with the
      highest dose of amlodipine. All doses produced significant reductions in angina
      attack frequency and the rate of nitroglycerin consumption. Amlodipine was well
      tolerated and no patients were withdrawn due to adverse events or laboratory
      abnormalities.

PMID- 16296710
TI  - A 6-week double-blind comparison of amlodipine and placebo in patients with
      stable exertional angina pectoris receiving concomitant beta-blocker therapy.
AB  - This study was a multicenter, double-blind comparison of the antianginal efficacy
      and safety of amlodipine and placebo as adjunctive therapy with constant
      recommended maintenance doses of beta-blockers. Patients with stable exertional
      angina pectoris were randomized to placebo or amlodipine at a starting dose of 5
      mg once daily. The amlodipine dose was adjusted to 10 mg daily after 2 weeks if
      angina attacks were not abolished. Antianginal efficacy was assessed throughout
      the study with angina diaries, investigators' and patients' global evaluations,
      and with bicycle exercise tests during a placebo run-in period (baseline) and
      after 2 and 6 weeks of double-blind treatment. On baseline-final analysis, the
      exercise time to angina onset increased by 13% with amlodipine compared to 6%
      with placebo (p < 0.05). The total exercise time increased by 11% on amlodipine
      compared with 2% on placebo, though this difference did not reach statistical
      significance. Angina attack frequency and nitroglycerin consumption were both
      reduced by adding amlodipine to beta-blocker treatment. Amlodipine in combination
      with beta-blocker therapy was well tolerated, with a low incidence of side
      effects and laboratory test abnormalities. The study showed clearly that addition
      of amlodipine to beta-blocker therapy in patients with stable angina pectoris was
      well tolerated and gave improved antianginal efficacy.

PMID- 16296711
TI  - An 8-week double-blind study of amlodipine and diltiazem in patients with stable
      exertional angina pectoris.
AB  - A multicenter, double-blind study was performed to compare the antianginal
      efficacy and safety of the new dihydropyridine calcium antagonist amlodipine with
      the benzothiazepine calcium antagonist diltiazem in patients with stable
      exertional angina pectoris. Following a 2-week placebo run-in period, 39 patients
      were randomized to receive amlodipine (2.5-10 mg once daily) and 41 patients to
      receive diltiazem (60-120 mg three times daily) in an 8-week double-blind
      treatment phase. The study used standardized bicycle exercise testing as a
      primary efficacy assessment. Patients also recorded angina frequency and
      nitroglycerin (NTG) tablet consumption/ week. Treatment with amlodipine and
      diltiazem resulted in an improvement in total exercise time, time to angina and
      total work, mean ST-segment deviation at maximum common load, median number of
      angina attacks/week, and NTG tablet consumption/week. The incidence and severity
      of possibly treatment-related side effects and laboratory test abnormalities were
      comparable for both drugs. The most frequently reported side effects were
      dizziness, headache, peripheral edema, and nausea. Two patients withdrew from
      diltiazem treatment due to pruritus in one case and severe headache and moderate
      dyspnea in the other. No amlodipine-treated patients withdrew due to side
      effects. In conclusion, this study demonstrated that the antianginal efficacy and
      tolerability of amlodipine is equivalent to diltiazem, but amlodipine has the
      advantage of once-daily dosing.

PMID- 16296712
TI  - Open comparative study to assess the efficacy and safety of two calcium
      antagonists: amlodipine and diltiazem in the treatment of symptomatic myocardial
      ischemia.
AB  - The efficacy and safety of amlodipine (5-10 mg once daily) and diltiazem (30-60
      mg three times daily) were compared in 40 patients with symptomatic myocardial
      ischemia. A 2-week placebo run-in period was followed by 10 weeks of open
      treatment with amlodipine (n = 20) or diltiazem (n = 20). Concomitant treatment
      with other antianginal drugs (except other calcium antagonists) was permitted
      throughout the study. The baseline blood pressures were 166/93 and 160/91 mm Hg
      for the amlodipine group and diltiazem groups, respectively. Amlodipine (mean
      final daily dose of 9.25 mg) reduced blood pressure by - 27/-11 mm Hg compared
      with a reduction of - 17/-8 mm Hg for diltiazem (mean final daily dose of 180
      mg), with no significant effects on heart rate. A significantly greater reduction
      in the mean rate-pressure product was observed after amlodipine (-20.8%) when
      compared with diltiazem (-13.1%) (p < 0.05). Amlodipine reduced the mean weekly
      angina attacks to zero after 6 weeks of treatment (baseline of 3.4 attacks/week)
      compared with a reduction from 3.3 to 0.35 attacks/week after 10 weeks of
      treatment with diltiazem. The amlodipine group had a reduction in mean
      nitroglycerin consumption from baseline of 1.1 mg/week to zero by week 6, whereas
      the diltiazem group had reduced mean weekly intake from 0.9 to 0.1 mg at the end
      of the study. The overall assessment of clinical efficacy was excellent for 100%
      of amlodipine patients compared with 40% of diltiazem patients. The high-density
      lipoprotein cholesterol/total cholesterol ratio increased by 15.8% with
      amlodipine compared to diltiazem, which produced a 4.5% decrease. Amlodipine
      decreased triglycerides by 7.1% compared to 4.5% with diltiazem. The incidence
      and severity of side effects was comparable for both treatments. Amlodipine once
      daily was effective and well tolerated in the treatment of patients with
      symptomatic myocardial ischemia and was comparable with diltiazem three times
      daily.

PMID- 16296713
TI  - An open multicenter efficacy and safety evaluation of amlodipine in the treatment
      of symptomatic myocardial ischemia.
AB  - The efficacy and safety of amlodipine (5-10 mg) once daily were studied in an
      open study in patients with symptomatic myocardial ischemia. The study is ongoing
      and this report is based on an interim analysis of data from 78 patients. A 2
      week baseline period in which patients maintained their current antianginal
      therapy was followed by a 10-week treatment period with 5-10 mg of
      amlodipine/day. Both the median number of angina attacks per week and the median
      number of nitroglycerin (NTG) tablets consumed/week were significantly reduced
      after amlodipine (mean daily dose of 8.6 mg) when compared with baseline (p <
      0.05). A total of 98.4% of patients (63/64) experienced a reduction in the
      frequency of angina attacks/week and 91% of patients (58/64) had angina attacks
      reduced to < or = 2/week. In self-assessments, 95% of patients (55/58) reported
      improved angina control and 91% (53/58) felt their ability to perform usual
      activities had improved. Twenty-seven patients experienced adverse events
      reported as drug related. The most common adverse event noted was edema.
      Amlodipine once daily significantly reduced the incidence of angina attacks and
      the concomitant need of nitroglycerin for relief of symptoms and thus improved
      the patients' ability to perform daily activities. Most adverse events reported
      were mild or moderate and the incidence is as would be expected in this patient
      population.

PMID- 16296715
TI  - Technology versus products--what's the real driving force of interest for the
      pharmaceutical industry?

PMID- 16296714
TI  - An update on the safety of amlodipine.
AB  - A previous article on the safety of amlodipine reviewed data from over 4,000
      subjects who participated in clinical trials sponsored by Pfizer Central
      Research. Once-daily amlodipine was shown to be a well-tolerated treatment of
      hypertension and myocardial ischemia. Although amlodipine is a potent
      vasodilator, there was a low incidence of side effects such as headache,
      flushing, and dizziness. Amlodipine was not associated with adverse effects on
      hematologic or biochemical safety parameters nor on serum cholesterol or
      triglyceride levels. Amlodipine did not alter electrical conduction in the heart.
      Amlodipine had a favorable safety profile in comparative trials vs. beta
      blockers. The data base of comparative trials vs. other calcium antagonists was
      small but the toleration of amlodipine was similar to that of verapamil and
      diltiazem. No data from comparative trials vs. another calcium antagonist of the
      dihydropyridine class have been available. This article reviews data from
      recently completed trials vs. nitrendipine and from trials in which amlodipine
      was used in combination with other agents. Amlodipine was better tolerated than
      nitrendipine and had a much lower incidence of side effects usually related to
      vasodilatation. This difference in side-effect profile was especially marked
      during the first days of treatment. Amlodipine was well tolerated when used in
      combination with beta-blockers, diuretics, ACE inhibitors, and nitrates. The
      gradual onset of action and relatively long half-life of amlodipine are the
      probable cause for the improved toleration in comparison with other
      dihydropyridines. Besides the low incidence of trivial side effects, increasing
      clinical experience with amlodipine provides no evidence that amlodipine is a
      cause of rare but serious adverse effects. It is concluded that amlodipine is an
      antihypertensive and anti-ischemic agent that has the combined advantages of a
      good safety profile with once-daily dosage and a smooth onset and long duration
      of action.

PMID- 16296716
TI  - Delivery of biologicals: the wish list is long...
AB  - In this editorial, a wish list is drawn up for future research and development
      activities regarding biologicals.

PMID- 16296717
TI  - Tumour-selective drug delivery via folate receptor-targeted liposomes.
AB  - Tumour cell-targeted liposomal delivery has the potential to enhance the
      therapeutic efficacy and reduce the toxicity of anticancer agents. Folate
      receptor (FR) expression is frequently amplified among human malignancies. FR is,
      therefore, potentially useful as a tumour marker for targeted drug delivery. FR
      mediated liposomal delivery has been shown to enhance the antitumour efficacy of
      doxorubicin both in vitro and in vivo, and to overcome P-glycoprotein-mediated
      multi-drug resistance. In addition, FR-targeted liposomes have shown utility as
      effective delivery vehicles of genes and antisense oligodeoxyribonucleotides to
      FR(+) tumour cells. Both solid tumours and leukaemias can potentially benefit
      from FR-targeted drug delivery. Multiple mechanisms might contribute to greater
      therapeutic efficacy for FR-targeted liposomes, such as FR-dependent cytotoxicity
      and antiangiogenic activity. Further investigation of this promising drug
      delivery strategy is clearly warranted.

PMID- 16296718
TI  - Growth factor delivery for bone tissue repair: an update.
AB  - Growth factors (GFs) are endogenous proteins capable of acting on cell-surface
      receptors and directing cellular activities involved in the regeneration of new
      bone tissue. The specific actions and long-term effects of GFs on bone-forming
      cells have resulted in exploration of their potential for clinical bone repair.
      The concerted efforts have led to the recent approval of two GFs, bone
      morphogenetic protein-2 and osteogenic protein-1, for clinical bone repair, and
      human parathryroid hormone (1-34) for augmentation of systemic bone mass. This
      review provides a selective summary of recent (2001-2004) attempts for GF
      delivery in bone tissue regeneration. First, a summary of non-human primate
      studies involving local regeneration and repair is provided, with special
      emphasis on the range of biomaterials used for GF delivery. Next, efforts to
      administer GFs for systemic augmentation of bone tissue are summarised. Finally,
      an alternative means of GF delivery, namely the delivery of genes coding for
      osteogenic proteins, rather than the delivery of the proteins, is summarised from
      rodent models. To conclude, future avenues of research considered promising to
      enhance the clinical application of GFs are discussed.

PMID- 16296720
TI  - Carbon nanotubes for the delivery of therapeutic molecules.
AB  - Functionalised carbon nanotubes (f-CNTs) are emerging as new tools in the field
      of nanobiotechnology and nanomedicine. This is because they can be easily
      manipulated and modified by encapsulation with biopolymers or by covalent linking
      of solubilising groups to the external walls and tips. The possibility of
      incorporating f-CNTs into biological systems has opened the way to the
      exploration of their potential applications in biology and medicinal chemistry.
      Within the different fields of applications (i.e., biosensors, composite
      materials, molecular electronics), one use of CNTs is as new carrier systems for
      the delivery of therapeutic molecules. Research discussed in this review is
      focused on recent advances in the development of CNT technology for the delivery
      of drugs, antigens and genes.

PMID- 16296721
TI  - Dry powder inhalers for pulmonary drug delivery.
AB  - The pulmonary route is an interesting route for drug administration, both for
      effective local therapy (asthma, chronic obstructive pulmonary disease or cystic
      fibrosis) and for the systemic administration of drugs (e.g., peptides and
      proteins). Well-designed dry powder inhalers are highly efficient systems for
      pulmonary drug delivery. However, they are also complicated systems, the the
      performance of which relies on many aspects, including the design of the inhaler
      (e.g., resistance to air flow and the used de-agglomeration principle to generate
      the inhalation aerosol), the powder formulation and the air flow generated by the
      patient. The technical background of these aspects, and how they may be tuned in
      order to obtain desired performance profiles, is reviewed. In light of the
      technical background, new developments and possibilities for further improvements
      are discussed.

PMID- 16296722
TI  - Thiomers for oral delivery of hydrophilic macromolecular drugs.
AB  - In recent years thiolated polymers (thiomers) have appeared as a promising new
      tool in oral drug delivery. Thiomers are obtained by the immobilisation of thio
      bearing ligands to mucoadhesive polymeric excipients. By the formation of
      disulfide bonds with mucus glycoproteins, the mucoadhesive properties of thiomers
      are up to 130-fold improved compared with the corresponding unmodified polymers.
      Owing to the formation of inter- and intramolecular disulfide bonds within the
      thiomer itself, matrix tablets and particulate delivery systems show strong
      cohesive properties, resulting in comparatively higher stability, prolonged
      disintegration times and a more controlled drug release. The permeation of
      hydrophilic macromolecular drugs through the gastrointestinal (GI) mucosa can be
      improved by the use of thiomers. Furthermore, some thiomers exhibit improved
      inhibitory properties towards GI peptidases. The efficacy of thiomers in oral
      drug delivery has been demonstrated by various in vivo studies. A pharmacological
      efficacy of 1%, for example, was achieved in rats by oral administration of
      calcitonin tablets comprising a thiomer. Furthermore, tablets comprising a
      thiomer and pegylated insulin resulted in a pharmacological efficacy of 7% after
      oral application to diabetic mice. Low-molecular-weight heparin embedded in
      thiolated polycarbophil led to an absolute bioavailability of > or = 20% after
      oral administration to rats. In these studies, formulations comprising the
      corresponding unmodified polymer had only a marginal or no effect. These results
      indicate drug carrier systems based on thiomers appear to be a promising tool for
      oral delivery of hydrophilic macromolecular drugs.

PMID- 16296723
TI  - Periocular routes for retinal drug delivery.
AB  - Despite numerous scientific efforts, delivery of therapeutic amounts of a drug to
      the retina remains a challenge. This challenge is compounded if chronic therapy
      is desired. The inability or inefficiency of topical and systemic routes for
      retinal delivery of existing drugs is now widely accepted. Although the
      intravitreal route offers high local concentrations in the vitreous and, hence,
      retina, these advantages are offset by side effects, such as cataracts,
      endophthalmitis and retinal detachment, following repeated intravitreal
      injections, or intravitreal placement of sustained-release implants. As discussed
      in this review, periocular routes, including subconjunctival, sub-tenon,
      retrobulbar, peribulbar and posterior juxtascleral routes, potentially offer a
      more promising alternative for enhanced drug delivery to the retina compared with
      topical and systemic routes. Periocular routes exploit the permeability of sclera
      for retinal drug delivery, and they are particularly useful for administering
      sustained-release systems of potent drugs. This review discusses the various
      periocular routes with respect to their anatomical location, pharmacokinetics,
      safety and mechanisms of drug delivery. In the coming years, several innovations
      in absorption enhancement, drug delivery systems and drug administration devices
      are anticipated for improving retinal drug delivery via periocular routes.

PMID- 16296719
TI  - Ultrasonic drug delivery--a general review.
AB  - Ultrasound has an ever-increasing role in the delivery of therapeutic agents,
      including genetic material, protein and chemotherapeutic agents. Cavitating gas
      bodies, such as microbubbles, are the mediators through which the energy of
      relatively non-interactive pressure waves is concentrated to produce forces that
      permeabilise cell membranes and disrupt the vesicles that carry drugs. Thus, the
      presence of microbubbles enormously enhances ultrasonic delivery of genetic
      material, proteins and smaller chemical agents. Numerous reports show that the
      most efficient delivery of genetic material occurs in the presence of cavitating
      microbubbles. Attaching the DNA directly to the microbubbles, or to gas
      containing liposomes, enhances gene uptake even further. Ultrasonic-enhanced gene
      delivery has been studied in various tissues, including cardiac, vascular,
      skeletal muscle, tumour and even fetal tissue. Ultrasonic-assisted delivery of
      proteins has found most application in transdermal transport of insulin.
      Cavitation events reversibly disrupt the structure of the stratus corneum to
      allow transport of these large molecules. Other hormones and small proteins could
      also be delivered transdermally. Small chemotherapeutic molecules are delivered
      in research settings from micelles and liposomes exposed to ultrasound.
      Cavitation appears to play two roles: it disrupts the structure of the carrier
      vesicle and releases the drug; and makes cell membranes and capillaries more
      permeable to drugs. There remains a need to better understand the physics of
      cavitation of microbubbles and the impact that such cavitation has on cells and
      drug-carrying vesicles.

PMID- 16296724
TI  - Reducing the immunostimulatory activity of CpG-containing plasmid DNA vectors for
      non-viral gene therapy.
AB  - The mammalian innate immune system has the ability to recognise and direct a
      response against incoming foreign DNA. The primary signal that triggers this
      response is unmethylated CpG motifs present in the DNA sequence of various
      disease-causing pathogens. These motifs are rare in vertebrate DNA, but abundant
      in bacterial and some viral DNAs. Because gene therapy generally involves the
      delivery of DNA from either plasmids of bacterial origin or recombinant viruses,
      an acute inflammatory response of variable severity inevitably results. The
      response is most serious for non-viral gene delivery vectors composed of cationic
      lipid-DNA complexes, producing adverse effects at lower doses and lethality at
      higher doses of complex. This review examines the role of immunostimulatory CpG
      motifs in the acute inflammatory response to non-viral gene therapy vectors.
      Strategies to neutralise or eliminate CpG motifs within plasmid DNA vectors, and
      the existing limitations of CpG reduction on improving the safety profile of non
      viral vectors, will be discussed.

PMID- 16296726
TI  - Particle uptake by Peyer's patches: a pathway for drug and vaccine delivery.
AB  - Particle uptake by Peyer's patches offers the possibility of tailoring vaccines
      that can be delivered orally. However, particle uptake by the follicle-associated
      epithelium in the gastrointestinal tract depends on several different factors
      that are the physicochemical properties of the particles, the physiopathological
      state of the animal, the analytical method used to evaluate the uptake and
      finally the experimental model. These parameters do not allow a clear idea about
      the optimal conditions to target the Peyer's patches. The goal of this review is
      to clarify the role of each factor in this uptake.

PMID- 16296727
TI  - Adaptive Aerosol Delivery (AAD) technology.
AB  - Jet nebulisers have, since the 1920s, been used for delivery of inhaled drugs for
      the treatment of asthma, chronic-obstructive pulmonary disease and pulmonary
      infections. During the last two decades, recognition of the shortcomings of
      conventional nebulisers has led to the development of new "intelligent"
      nebulisers such as the Adaptive Aerosol Delivery (AAD), Profile Therapeutics, a
      Respironics company) systems. Diseases of the airways have traditionally been
      logical candidates for treatment with inhaled drugs. The introduction of the
      "intelligent" nebulisers has, however, broadened the possibilities for inhaled
      treatment to include drugs targeted for systemic diseases. These nebulisers offer
      the possibility to deliver more precise doses of drug, maximise lung deposition,
      enhance adherence to treatment and compliance with the device through feedback to
      the patient, and last but not least, offer the possibility to reduce nebulisation
      times.

PMID- 16296728
TI  - Medical and pharmaceutical nanoengineering conference/International conference on
      MEMS, nano and smart systems.
AB  - Researchers representing all the northern hemispheric continents gathered for 3
      days in Banff, Canada, to hear a wide range of talks on the application of micro-
      and nanotechnology to drug delivery. Topics included nanotubes, nanoparticles,
      liposomes, micelles, novel inhaled aerosols, antibody engineering and vaccines.
      Also featured were talks on the application of micro- and nanotechnology to
      diagnostics, including microfluidics, as well as biomolecular computing. The
      conference showcased the first demonstration of preliminary concepts for "smart
      particle aerosols", in which nanofabrication methods are used to produce inhaled
      aerosol particles with "intelligent" features. The conference provided an
      excellent forum for cross-fertilisation and discussion between disciplines, with
      attendees covering a broad range of areas in engineering and the physical and
      life sciences that are not often found together at a single conference. This
      breadth of attendees and topics provided a highly stimulating environment. An
      invitation to next year's conference (24-29 July 2005, Banff, Alberta, Canada)
      was extended, as listed at the conference website [101].

PMID- 16296725
TI  - Intracellular trafficking of nucleic acids.
AB  - Until recently, the attention of most researchers has focused on the first and
      last steps of gene transfer, namely delivery to the cell and transcription, in
      order to optimise transfection and gene therapy. However, over the past few
      years, researchers have realised that the intracellular trafficking of plasmids
      is more than just a "black box" and is actually one of the major barriers to
      effective gene delivery. After entering the cytoplasm, following direct delivery
      or endocytosis, plasmids or other vectors must travel relatively long distances
      through the mesh of cytoskeletal networks before reaching the nuclear envelope.
      Once at the nuclear envelope, the DNA must either wait until cell division, or be
      specifically transported through the nuclear pore complex, in order to reach the
      nucleoplasm where it can be transcribed. This review focuses on recent
      developments in the understanding of these intracellular trafficking events as
      they relate to gene delivery. Hopefully, by continuing to unravel the mechanisms
      by which plasmids and other gene delivery vectors move throughout the cell, and
      by understanding the cell biology of gene transfer, superior methods of
      transfection and gene therapy can be developed.

PMID- 16296729
TI  - The second annual symposium on nanomedicine and drug delivery: exploring recent
      developments and assessing major advances. 19-20 August 2004, Polytechnic
      University, Brooklyn, NY, USA.
AB  - The meeting was dedicated to novel aspects of nanomedicine, including polymer
      drug delivery systems (DDS) and biomaterials. Self-assembled micellar DDS have
      been evaluated in terms of morphology, biological properties, and results of
      clinical trials. Important advances in the design of nanoparticles as DDS have
      been highlighted in various presentations. Unexpected issues of polymer-related
      biological effects, including gene expression, were stressed in relation to
      polymer DDS. Great potential of nanofabrication of biomaterials, and preliminary
      data on the design of polymer scaffolds were demonstrated in a number of reports.
      This symposium demonstrated how timely the development of nanosised DDS is, with
      advances in understanding the disease-related mechanisms, and outlined the major
      areas of application of nanomedicine technology.

PMID- 16296730
TI  - Innovative therapeutics: from molecules to medicines. 27 June-7 July 2004, Parma,
      Italy.
AB  - The Socrates Intensive Programme offers annual courses focusing on the specific
      aspects of innovative therapeutics. The 2004 meeting was coordinated by the
      University of Parma and covered various subjects in the field of advanced drug
      delivery and pharmaceutical technology, including sessions on biopharmaceutics,
      pharmacokinetics, polymers, oral delivery, colloidal vectors, peptide and protein
      delivery, vaccines, oligonucleotide delivery, gene delivery, non-conventional
      routes of administration, and a graduate student symposium. The meeting had a
      highly interactive character and provided a unique opportunity for young
      scientists to present and discuss their work in an international setting.

PMID- 16296731
TI  - Drug delivery for optimised products: from product life-cycle management to first
      generation product concepts.

PMID- 16296733
TI  - Commercial challenges of protein drug delivery.
AB  - The discovery of insulin in 1922 marked the beginning of research and development
      to improve the means of delivering protein therapeutics to patients. From that
      period forward, investigators have contemplated every possible route of delivery.
      Their research efforts have followed two basic pathways: one path has focused on
      non-invasive means of delivering proteins to the body; and the second path has
      been primarily aimed at increasing the biological half-life of the therapeutic
      molecules. Thus far, the commercial successes of protein delivery by the nasal,
      oral and pulmonary routes have been more opportunistic rather than the
      application of platform technologies applicable to every protein or peptide. In
      several limited cases, sustained delivery of peptides and proteins has employed
      the use of polymeric carriers. More successes have been achieved by chemical
      modification using amino acid substitutions, protein pegylation or glycosylation
      to improve the pharmacodynamic properties of certain macromolecules. Today,
      commercial successes for protein and peptide delivery systems remain limited. The
      needle and syringe remain the primary means of protein delivery. Major hurdles
      remain in order to overcome the combined natural barriers of drug permeability,
      drug stability, pharmacokinetics and pharmacodynamics of protein therapeutics.

PMID- 16296732
TI  - Modulation of gene expression by antisense and antigene oligodeoxynucleotides and
      small interfering RNA.
AB  - Antisense oligodeoxynucleotides, triplex-forming oligodeoxynucleotides and double
      stranded small interfering RNAs have great potential for the treatment of many
      severe and debilitating diseases. Concerted efforts from both industry and
      academia have made significant progress in turning these nucleic acid drugs into
      therapeutics, and there is already one FDA-approved antisense drug in the clinic.
      Despite the success of one product and several other ongoing clinical trials,
      challenges still exist in their stability, cellular uptake, disposition, site
      specific delivery and therapeutic efficacy. The principles, strategies and
      delivery consideration of these nucleic acids are reviewed. Furthermore, the ways
      to overcome the biological barriers are also discussed so that therapeutic
      concentrations at their target sites can be maintained for a desired period.

PMID- 16296734
TI  - Recent advances in the use of protein transduction domains for the delivery of
      peptides, proteins and nucleic acids in vivo.
AB  - Protein transduction domains (PTDs) are small cationic peptides that can
      facilitate the uptake of large, biologically active molecules into mammalian
      cells. Recent reports have shown that PTDs can mediate the delivery of cargo to
      tissues throughout a living organism. Such technology could eliminate the size
      restrictions on usable drugs, so enabling previously unavailable large molecules
      to modulate in vivo biology and alleviate disease. This article will review the
      evidence that PTDs can be used both to deliver active molecules to pathological
      tissue in vivo and to treat models of disease such as cancer, ischaemia and
      inflammation.

PMID- 16296735
TI  - Propellant-driven metered-dose inhalers for pulmonary drug delivery.
AB  - The current market for pulmonary drug delivery is at a bottleneck. The
      therapeutic advantages of inhalation aerosols, and the potential for the lungs as
      a route for systemically acting drugs, vaccines and gene therapeutic agents, have
      resulted in a rapid growth of the industry. Alongside this, the environment of
      inhaler design and formulation has changed markedly in recent years.
      Environmental concerns over propellants, the commercial success of dry powder
      inhalers, and the apparent lack of advancement of propellant-driven metered-dose
      inhalers (pMDIs) has led to a less clear future for these devices. This review
      critically assesses these pressures and also potential opportunities for the
      pMDI. It is proposed that the future role of pMDIs will be determined by several
      important forces that can be classified under 'technology development' or 'market
      climate' categories. Technology development forces will be strengthened by the
      ability of the industry to have a systematic understanding of mechanisms of spray
      formation, perform subsequent and continued device and formulation advances, and
      a focus on all patient groups: particularly paediatric and geriatric populations.
      The ability to succeed in these areas will be largely determined by the
      willingness to invest in fundamental research of pMDI technologies.

PMID- 16296736
TI  - Solid lipid microparticles: formulation, preparation, characterisation, drug
      release and applications.
AB  - This review details the properties of solid lipid microparticles (SLMs): a
      promising drug carrier system that has been until now rather unexploited. First,
      the advantages of SLMs compared with other drug carrier systems are listed. Then
      an overview of SLM manufacturing compounds and techniques is presented. A
      detailed discussion of the characteristics of SLMs follows, and includes the
      determination of particle size distribution, the determination of SLM morphology,
      the solid-state analysis, the determination of SLM drug loading and the factors
      influencing it. The in vitro drug release studies that have been carried out so
      far and the parameters affecting them are also described. Some preliminary in
      vivo aspects (in vivo drug release studies, biocompatibility studies and in vivo
      fate) are also considered.

PMID- 16296737
TI  - Targeted drug delivery to mammalian mitochondria in living cells.
AB  - Mitochondrial dysfunction causes or contributes to a large number of human
      disorders including neuromuscular and neurodegenerative diseases, diabetes,
      ischaemia-reperfusion injury and cancer. Increasing efforts are being made
      towards mitochondria-directed pharmacological intervention, leading to the
      emergence of 'mitochondrial medicine' as a new field of biomedical research. The
      identification of new molecular mitochondrial drug targets in combination with
      the development of methods for selectively delivering biologically active
      molecules to the site of mitochondria will eventually launch new therapies for
      the treatment of mitochondria-related diseases, based either on the selective
      protection, repair or eradication of cells. This review discusses the need for
      the development of mitochondria-specific drug and DNA delivery systems, and
      evaluates the currently employed strategies for mitochondrial drug targeting,
      including some of their potential therapeutic applications.

PMID- 16296738
TI  - Strategies for enhanced radiation delivery in patients with lung cancer.
AB  - Since the 1970s primary management for regionally advanced non-small cell lung
      cancer has shifted from radiotherapy alone to sequential chemoradiation to
      concurrent chemoradiation. The increase in survival with these approaches has
      been small; an approximately 3-4 month per decade increase in median survival.
      Future avenues to improve on these outcomes could involve: i)dose-intense
      radiotherapy; ii) better target delineation; and iii) combining molecularly
      targeted agents with optimised radiation therapy. However, to accomplish this,
      techniques to control tumour motion and decrease toxicity must be developed.

PMID- 16296739
TI  - Transdermal and topical pharmacotherapy for male sexual dysfunction.
AB  - Transdermal and topical pharmacotherapies have been used for the treatment of
      male sexual dysfunctions for some time and are well-accepted treatment modalities
      for these conditions. A Medline search was conducted for transdermal and topical
      medications, examining published literature over the past two decades. From this
      search a comprehensive review has been compiled of the available transdermal and
      topical treatment options for the treatment of male sexual dysfunctions,
      particularly erectile dysfunction, Peyronie's disease and hypogonadism. It is
      likely that the transdermal and topical drug armamentarium for sexual
      dysfunction, male and female, will grow over the next decade.

PMID- 16296740
TI  - New methylphenidate formulations for the treatment of attention
      deficit/hyperactivity disorder.
AB  - dl-Methylphenidate (MPH) remains the most widely used pharmacological agent in
      the treatment of attention-deficit/hyperactivity disorder (ADHD). The
      predominantly dopaminergic mechanism of the psychostimulant actions has become
      more clearly defined. Neuroimaging and genetic studies are revealing the
      underlying neuropathology in ADHD. Novel extended-release (ER) MPH formulations
      now offer drug delivery options to overcome both the short-term actions of
      immediate-release (IR) MPH and the acute tolerance associated with the first
      generation ER-MPH products. These novel MPH products apply proprietary
      technologies such as OROS (Alza), Diffucaps (Eurand) and SODAS (Elan) to offer
      both the convenience of once-a-day administration and absorption profiles
      resembling, to varying degrees, the standard multiple dose schedules of IR-MPH.
      The pharmacodynamics of the separate MPH enantiomers is in the process of further
      neuropharmacological characterisation. It is well established that dl-MPH
      undergoes marked stereoselective metabolism. Although l-MPH exhibits only minimal
      oral absorption, it may preferentially penetrate the brain, and interacts with
      ethanol to form the metabolite ethylphenidate. The newly approved resolved
      enantiomer product d-MPH is now available in an IR formulation, and when
      administered at one-half the dose to that of the racemate, is purported to
      produce a longer duration of clinical effect, despite essentially identical
      pharmacokinetics. A long-acting formulation of d-MPH, which employs the SODAS
      technology, is in the advanced stages of clinical development.

PMID- 16296741
TI  - Targeted polymers for gene delivery.
AB  - Over the past decade, significant research has been done in the area of polymer
      mediated gene delivery. Synthesis of new polymers and modifications to existing
      polymers has resulted in polyplexes with improved in vitro and in vivo
      transfection efficiencies. Targeting has been an important aspect of this
      research, and various strategies for obtaining selective and enhanced gene
      delivery to the target site have been evaluated. This review covers the different
      aspects involved in polyplex targeting. Development of targeted polyplexes
      involves a careful consideration of the target site, the targeting ligand and the
      physicochemical properties of the polyplex itself. The need to redirect the
      polyplexes by using the 'shield and target' approach by reducing nonspecific
      interactions with negatively charged components, while conferring specificity by
      incorporating targeting ligands, is discussed. Basic chemistry involved in
      modifying polymers is covered and examples of targeting strategies used for
      tissue-specific gene delivery are discussed. Targeting is also discussed in the
      broader context of developing safe and effective polymeric vectors for in vivo
      gene delivery. Maximum benefit of targeting can be obtained when it is used as
      part of a multi-functional complex containing elements designed to improve gene
      delivery and reduce overall toxicity of the polyplex.

PMID- 16296742
TI  - TARGIT technology: coated starch capsules for site-specific drug delivery into
      the lower gastrointestinal tract.
AB  - TARGIT technology (West Pharmaceutical Services) is designed for site-specific
      delivery of drugs in the gastrointestinal (GI) tract and, in particular, targeted
      release into the colonic region. A key area of application is the delivery of
      therapeutic agents for local treatment of lower GI diseases. The technology is
      based on the application of pH-sensitive coatings onto injection-moulded starch
      capsules. An extensive body of clinical data has been generated showing reliable
      in vivo performance of the capsules. In gamma-scintigraphy studies around 90% of
      TARGIT capsules (n = 84) delivered their contents to the target site of the
      terminal ileum and colon. TARGIT-based products are in active clinical
      development for the treatment of conditions including inflammatory bowel
      diseases.

PMID- 16296743
TI  - Biochronomer technology.
AB  - Biochronomer (AP Pharma) is a fourth-generation poly(ortho ester) prepared by the
      condensation of diols and a diketene acetal. The polymer contains a copolymerised
      latent acid whose concentration controls erosion rate. The polymer has been shown
      to undergo a surface erosion process and a number of applications have been
      explored. Among these, the delivery of plasmid DNA for vaccines is currently of
      most interest. This application takes advantage of the acid-labile nature of the
      polymer, which leads to rapid polymer hydrolysis and hence rapid release of
      plasmid DNA once internalised in the acidic environment within the endosomes, and
      the non-acidic environment within the polymer that conserves plasmid DNA
      conformation. A low molecular semisolid polymer is now in Phase II clinical
      trials for the delivery of mepivacaine to control postoperative pain, and in
      Phase I clinical trials for the systemic delivery of granisetron to control
      nausea.

PMID- 16296744
TI  - Drug delivery global summit--evaluating emerging technologies.
AB  - Two day-long sessions at the Drug delivery global summit, organised by SMi Group
      Ltd, were devoted to discussion on critical aspects of drug delivery, including
      advances in drug delivery systems and their applications to new products, with a
      primary focus on oral systems, but also highlighting recent progress in
      inhalation, parenteral and transdermal delivery. The event included case studies
      from big pharma, biotech and drug delivery companies to illustrate emerging
      delivery technologies and how they can be applied to develop innovative products.
      The conference created a platform for discussion on a range of topics from
      scientific issues and challenges to ways of establishing mutually beneficial
      relationships between technology and pharma companies.

PMID- 16296745
TI  - 9th International drug delivery technologies & deal-making summit.
AB  - SRI's 9th International drug delivery summit analysed the current position of
      drug delivery technologies within the pharmaceutical industry. The classical
      position of drug delivery as a tool in life cycle management is currently
      expanding into the primary formulations or even into enabling positions. Using
      drug delivery as a platform for drug development or redevelopment was recognised
      as a trend in the industry which is supported by the rapidly growing portion of
      drug delivery enhanced products already sold as well as by industry initiatives
      supporting future growth of the sector.

PMID- 16296747
TI  - Transporters and receptors in ocular drug delivery: opportunities and challenges.
AB  - In this editorial, the opportunities and challenges of transporter/receptor
      mediated ocular drug delivery are discussed.

PMID- 16296748
TI  - Bioadhesive properties of pegylated nanoparticles.
AB  - The design of bioadhesive nanoparticles (NPs) for targeting specific sites within
      the gut remains a major challenge. One possible strategy to solve this problem
      may be the use of pegylated NPs. In general, these carriers display different
      bioadhesive properties to nondecorated NPs. Thus, pegylated NPs show a higher
      ability to interact with the small intestine mucosa rather than with the stomach.
      However, the type of surface conformation of polyethylene glycol chains appears
      to have a great influence on the behaviour of these NPs. Theoretically, the
      traditional 'brush' polyethylene glycol corona would facilitate the penetration
      of the pegylated particles through the mucus layer and the subsequent adhesive
      interaction with the mucosa, which would promote their absorption by intestinal
      enterocytes. On the contrary, pegylated NPs with a 'loop' conformation would
      increase the time of residence of the adhered fraction of particles in the
      mucosa.

PMID- 16296749
TI  - Pegylated IFNs for chronic hepatitis C: an update.
AB  - For over a decade, IFN-alpha(2) has been the standard treatment for chronic
      hepatitis C. However, the drug's rapid clearance and short half-life have led to
      low rates of sustained virological response. Pegylation is a well-established
      method of modifying the pharmacological properties of IFNs, causing significant
      improvements in pharmacokinetics, which in turn lead to improved efficacy. Two
      pegylated forms of IFN-alpha(2) have been developed: PEG-IFN-alpha(2b) and PEG
      IFN-alpha(2a), and their efficacy has been established in randomised, controlled
      trials. However, the two differ significantly in structure, in vitro activity and
      pharmacological properties, and this may translate into -differences in clinical
      efficacy. Comparative trials have been initiated that will provide insight into
      relative importance of pharmacokinetics, bioactivity and dosing regimen.

PMID- 16296750
TI  - Epidermal delivery of protein and DNA vaccines.
AB  - Targeting vaccines to the skin epidermis results in the activation of an immune
      inductive site that is rich in antigen-presenting cells. The superficial location
      of the skin makes it accessible to vaccine delivery. However, it is difficult to
      access the epidermis using needle and syringe delivery, and vaccine antigens are
      too large to be effectively delivered using standard topical formulations. Needle
      free vaccine delivery systems have been developed for efficient delivery of
      particulate vaccines into the epidermal tissue. Particle-mediated epidermal
      delivery of DNA vaccines is based on the delivery of DNA-coated gold particles
      directly into the cytoplasm and nuclei of living cells of the epidermis,
      facilitating DNA delivery and gene expression. Alternatively, protein vaccines
      can be formulated into a dense powder, which can be propelled into the skin
      epidermis by epidermal powder immunisation using similar delivery devices and
      principles, but in this instance the protein is delivered to the extracellular
      space. Preclinical and clinical data will be reviewed, demonstrating applications
      of epidermal vaccine delivery to a wide range of experimental infectious disease
      vaccines.

PMID- 16296751
TI  - Cationic liposomes for gene delivery.
AB  - Cationic liposome-DNA complexes (lipoplexes) constitute a potentially viable
      alternative to viral vectors for the delivery of therapeutic genes. This review
      will focus on various parameters governing lipoplex biological activity, from
      their mode of formation to in vivo behaviour. Particular emphasis is given to the
      mechanism of interaction of lipoplexes with cells, in an attempt to dissect the
      different barriers that need to be surpassed for efficient gene expression to
      occur. Aspects related to new trends in the formulation of lipid-based gene
      delivery systems aiming at overcoming some of their limitations will be covered.
      Finally, examples illustrating the potential of cationic liposomes in clinical
      applications will be provided.

PMID- 16296752
TI  - Electroporation for targeted gene transfer.
AB  - The utilisation of nonviral gene delivery methods has been increasing steadily,
      however, a drawback has been the relative low efficiency of gene transfer with
      naked DNA compared with viral delivery methods. In vivo electroporation, which
      has previously been used clinically to deliver chemotherapeutic agents, also
      enhances the delivery of plasmid DNA and has been used to deliver plasmids to
      several tissue types, particularly muscle and tumour. Recently, a large number of
      preclinical studies for a variety of therapeutic modalities have demonstrated the
      potential of electrically mediated gene transfer. Although clinical trials using
      gene transfer with in vivo electroporation have not as yet been realised, the
      tremendous growth of this technology suggests that the first trials will soon be
      initiated.

PMID- 16296753
TI  - Progress towards gene therapy for cystic fibrosis.
AB  - A decade ago it was widely anticipated that cystic fibrosis would be one of the
      first diseases to be treated by gene therapy. The difficult hurdle of cloning the
      responsible gene had been accomplished, its function was established and the lung
      appeared readily accessible for gene replacement. Since the first clinical trials
      for cystic fibrosis lung disease in the early 1990s it has become increasingly
      apparent that successful lung-directed gene therapy is significantly more complex
      than was first envisioned. Numerous obstacles including vector toxicity,
      inefficient transgene expression and limited vector production have delayed
      progress. An increased understanding of vector biology and host interaction has
      led to the development of novel strategies to enhance the efficiency and
      selectivity of gene delivery to the lung. Although significant challenges remain,
      there is now a realistic prospect of a clinically effective treatment in the next
      10 years.

PMID- 16296755
TI  - Targeted delivery across the blood-brain barrier.
AB  - The safest and most effective way of targeting drugs to the entire brain is via
      delivery systems directed at endogenous receptor-mediated uptake mechanisms
      present at the cerebral capillaries. Such systems have been shown to be effective
      in animal models including primates, but no clinical trials have been performed
      so far. This review focuses on the well-characterised transferrin and insulin
      receptor-targeted systems, as well as on the more recently described systems that
      use the low-density lipoprotein-related protein 1 receptor, the low-density
      lipoprotein-related protein 2 receptor (also known as megalin and glycoprotein
      330) or the diphtheria toxin receptor (which is the membrane-bound precursor of
      heparin-binding epidermal growth factor-like growth factor). The possibilities
      and limitations of these systems are compared and their future for human
      application is discussed.

PMID- 16296754
TI  - Advances in nasal drug delivery through tight junction technology.
AB  - New approaches for enhancing intranasal drug delivery based on recent discoveries
      on the molecular biology of tight junctions (TJ) are significantly improving the
      bioavailability of 'non-Lipinsky' small molecules, and peptide, protein and
      oligonucleotide drugs. As knowledge of the structure and function of the TJ has
      developed, so has the ability to identify mechanism-based TJ modulators using
      high-throughput molecular biology-based screening methods. The present review
      focuses on recent developments on the TJ protein complex as a lipid raft-like
      membrane microdomain, the emerging role of unique endocytic pathways in
      regulating TJ dynamics, and the utility of techniques such as RNA interference
      and phage display to study TJ components and identify novel peptides and related
      molecules that can modulate their function. Experimental and statistical
      methodologies used for the identification of new classes of TJ modulators are
      described, which are capable of reversibly opening TJ barriers with broad
      potential to significantly improve intranasal and, eventually, oral drug
      delivery. The development of an advanced intranasal formulation for the obesity
      therapeutic PYY(3-36), the endogenous Y2 receptor agonist is also reviewed.

PMID- 16296756
TI  - Erythrocyte-based drug delivery.
AB  - The use of a physiological carrier to deliver therapeutics throughout the body to
      both improve their efficacy while minimising inevitable adverse side effects, is
      an extremely fascinating perspective. The behaviour of erythrocytes as a delivery
      system for several classes of molecules (i.e., proteins, including enzymes and
      peptides, therapeutic agents in the form of nucleotide analogues, glucocorticoid
      analogues) has been studied extensively as they possess several properties, which
      make them unique and useful carriers. Furthermore, the possibility of using
      carrier erythrocytes for selective drug targeting to differentiated macrophages
      increases the opportunities to treat intracellular pathogens and to develop new
      drugs. Finally, the availability of an apparatus that permits the encapsulation
      of drugs into autologous erythrocytes has made this technology available in many
      clinical settings and competitive with other drug delivery systems.

PMID- 16296757
TI  - Alternative administration of camptothecin analogues.
AB  - In order to improve the therapeutic index of camptothecin (CPT) analogues,
      alternative administration of CPT analogues is being evaluated. Topotecan,
      irinotecan, rubitecan, lurtotecan and 9-aminocamptothecin have been administered
      orally with response rates equivalent to that seen after intravenous
      administration, where applicable. Oral availability and administration of some of
      the newer CPT analogues, including diflomotecan (BN80915) and grimatecan
      (ST1481), have also shown promising results. Aerosolisation of liposomal 9
      nitrocamptothecin has been studied in patients with advanced malignancies
      involving the lung, demonstrating systemic antitumour activity. Intrathecal
      administration of topotecan has been studied in children with refractory
      neoplastic meningitis. It is well tolerated and associated with some antitumour
      activity. Intraperitoneal administration of topotecan as consolidation therapy in
      patients with ovarian cancer has shown promising results. Transdermal
      administration of rubitecan has been studied in mice. So far, no CPT has been
      approved for an alternative route of administration.

PMID- 16296758
TI  - Cyclodextrins in drug delivery.
AB  - Cyclodextrins are a family of cyclic oligosaccharides with a hydrophilic outer
      surface and a lipophilic central cavity. Cyclodextrin molecules are relatively
      large with a number of hydrogen donors and acceptors and, thus, in general they
      do not permeate lipophilic membranes. In the pharmaceutical industry
      cyclodextrins have mainly been used as complexing agents to increase aqueous
      solubility of poorly soluble drugs, and to increase their bioavailability and
      stability. Studies in both humans and animals have shown that cyclodextrins can
      be used to improve drug delivery from almost any type of drug formulation.
      However, the addition of cyclodextrins to existing formulations without further
      optimisation will seldom result in acceptable outcome. Currently there are
      approximately 30 different pharmaceutical products worldwide containing
      drug/cyclodextrin complexes on the market.

PMID- 16296759
TI  - Closed-loop insulin delivery - what lies between where we are and where we are
      going?
AB  - Closed-loop insulin delivery in individuals with diabetes can potentially lead to
      near-normal glucose profiles. To this end, existing subcutaneous glucose sensors
      and external insulin pumps can be linked with an insulin delivery algorithm to
      create a completely automated closed-loop system. This paper reviews current
      research into the development of such a system, with particular emphasis on
      creating a system emulating the physiological properties of the beta-cell. Issues
      related to using subcutaneous interstitial fluid for glucose sensing and insulin
      delivery are reviewed. Criteria for optimising the system are discussed using
      historical data. Existing strategies for open-loop pump therapy are presented
      with the objective of defining a path to advance from the existing
      physician/patient determined insulin therapy to a completely automated system.

PMID- 16296761
TI  - The customised electronic nebuliser: a new category of liquid aerosol drug
      delivery systems.
AB  - Inhalation of aerosols is the preferred route of administration of pharmaceutical
      compounds to the lungs when treating various respiratory diseases. Inhaled
      antibiotics, hormones, peptides and proteins are potential candidates for direct
      targeting to the site of action, thus minimising systemic absorption, dilution
      and undesired side effects, as much lower doses (as low as a fiftieth) are
      sufficient to achieve a similar therapeutic effect, compared with oral
      administration. A quick relief from the symptoms and a good tolerance are the
      main advantages of aerosol therapy. A new class of electronic delivery device is
      now starting to enter the market. The eFlow electronic nebuliser (PARI GmbH,
      Germany) provides improved portability and, in some instances, cuts treatment
      time to only a fraction of what has been experienced with current nebulised
      therapy. Drug formulations and the device can be mutually adapted and matched for
      optimal characteristics to meet the desired therapeutic target. Reformulation of
      known and proven compounds in a liquid format are commercially attractive as they
      present a relatively low development risk for potential drug candidates and,
      thus, have become a preferred pathway for the development of new inhalation
      products.

PMID- 16296760
TI  - Drug delivery into the brain using poly(lactide-co-glycolide) microspheres.
AB  - Among the strategies developed for drug delivery into the CNS, locally controlled
      drug release by the way of an implantable polymeric device has been developed in
      recent years. The first polymeric devices developed were macroscopic implants
      needing open surgery for implantation. Over the last few years, poly(lactide-co
      glycolide) microspheres have been shown to be safe and promising for drug
      delivery into the brain. Poly(lactide-co-glycolide) is biodegradable and
      biocompatible with brain tissue. Due to their size, these microspheres can be
      easily implanted by stereotaxy in discrete, precise and functional areas of the
      brain without causing damage to the surrounding -tissue. Brain tumour treatments
      have been developed using this approach and clinical trials have been performed.
      Potential applications in neurodegenerative diseases have also been explored,
      particularly neurotrophic factor delivery and cell therapy.

PMID- 16296762
TI  - Iontophoretic drug delivery using the IOMED Phoresor system.
AB  - Iontophoresis, or electromotive drug administration, is a process that enhances
      the delivery of drugs through a biological membrane via the application of low
      intensity electrical current. This technology offers several advantages over oral
      and injection drug delivery. Key advantages of iontophoretic drug delivery
      include the avoidance of pain and potential for infection associated with needle
      injection, the ability to control the rate of drug delivery, the ability to
      programme the drug-delivery profile and the minimisation of local tissue trauma.
      Research using iontophoresis has shown delivery of a number of drug classes. By
      controlling the applied electric current one can tailor a dosage regimen with a
      drug delivery profile specific for an indication and the needs of the patient.
      Advances in iontophoretic electrode design, microelectronics and methods to
      optimise iontophoretic drug delivery have improved the ability to safely deliver
      both older, off-patent drugs, as well as new chemical entities being developed to
      treat a variety of diseases. In addition to transdermal applications, current
      research indicates that iontophoresis may prove to be a viable noninvasive drug
      delivery method for treating conditions that affect the back of the eye.

PMID- 16296764
TI  - Strategies to improve oral drug bioavailability.
AB  - Efforts to improve oral drug bioavailability have grown in parallel with the
      pharmaceutical industry. As the number and chemical diversity of drugs has
      increased, new strategies have been required to develop orally active
      therapeutics. The past two decades have been characterised by an increased
      understanding of the causes of low bioavailability and a great deal of innovation
      in oral drug delivery technologies, marked by an unprecedented growth of the drug
      delivery industry. The advent of biotechnology and consequent proliferation of
      biopharmaceuticals have brought new challenges to the drug delivery field. In
      spite of the difficulties associated with developing oral forms of this type of
      therapeutics, significant progress has been made in the past few years, with some
      oral proteins, peptides and other macromolecules currently advancing through
      clinical trials. This article reviews the approaches that have been successfully
      applied to improve oral drug bioavailability, primarily, prodrug strategies, lead
      optimisation through medicinal chemistry and formulation design. Specific
      strategies to improve the oral bioavailability of biopharmaceuticals are also
      discussed.

PMID- 16296766
TI  - Pectin-based oral drug delivery to the colon.
AB  - This review presents an overview of studies concerning oral formulations intended
      for site-specific drug delivery to the colon with pectin as the main excipient.
      The biological aspects covered include gastrointestinal transit and the enzymatic
      degradation of pectin. Scintigraphic methods demonstrating the functionality of
      pectin formulations are discussed. The main focus is on the various formulations
      reported, including matrix tablets, multiparticulate formulations as pellets and
      hydrogel beads, and pectin-based coatings. Also included is an evaluation of
      common excipients employed to improve colon specificity by crosslinking or
      increasing the hydrophobicity. Finally, properties of the pectin molecules that
      are important for successful formulations are examined. The conclusion is that
      the studies found in the literature provide an excellent platform for the
      development of pectin-based colon delivery systems.

PMID- 16296765
TI  - Treatment of onychomycosis with oral antifungal agents.
AB  - Onychomycosis is the most common nail disease and describes the invasion of the
      nail by fungi. Different clinical patterns of infection depend on the way and the
      extent by which fungi colonise the nail: distal subungual onychomycosis, proximal
      subungual onychomycosis, white superficial onychomycosis, endonyx onychomycosis
      and total dystropic onychomycosis. The type of nail invasion depends on both the
      fungus responsible and on host susceptibility. Treatment of onychomycosis depends
      on the clinical type of the onychomycosis, the number of affected nails and the
      severity of nail involvement. The goals for antifungal therapy are mycological
      cure and a normal looking nail. In this paper the treatment of onychomycosis with
      oral antifungal agents will be reviewed.

PMID- 16296767
TI  - Novel drug delivery strategies for the treatment of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) encompasses two idiopathic inflammatory diseases
      of the intestinal tract: Crohn's disease and ulcerative colitis. Existing therapy
      for IBD consists mainly of orally or rectally administered small drug molecules,
      such as 5-aminosalicylates and corticosteroids, or potent systemic immune
      suppressants. IBD presents a challenging target for drug delivery, particularly
      by the oral route, as, contrary to most therapeutic regimens, minimal systemic
      absorption and maximal intestinal wall drug levels are desired. Several delivery
      strategies are employed to achieve this goal, including the chemical modification
      of the drug molecules, the use of controlled- and delayed-release formulations
      and the use of bioadhesive particles. The goal of this review is to summarise
      existing IBD therapy and examine novel approaches in intestinal drug delivery.

PMID- 16296768
TI  - Liposomes in the treatment of inflammatory disorders.
AB  - This review focuses on the therapeutic utility of liposomes in the treatment of
      inflammatory disorders, and aims to offer the reader an overview of the in vivo
      results obtained with liposomally encapsulated anti-inflammatory and immune
      suppressive drugs. The past 30 years has clearly indicated the added value of
      liposomes in the search for solutions for the delivery problems encountered.
      However, only a few liposomal anti-inflammatory therapeutics have entered the
      clinic. Reasons for the hurdles existing in the translation of promising
      preclinical findings to clinical studies are discussed.

PMID- 16296769
TI  - Liposomal delivery of photosensitising agents.
AB  - Photodynamic therapy is a clinically approved treatment for cancer and noncancer
      diseases. This modality utilises light-activatable chemicals (photosensitising
      agents) to capture photons and use light energy for the production of cytotoxic
      reactive molecular species. Most photosensitisers that are in use clinically or
      in preclinical development are hydrophobic and tend to aggregate in the aqueous
      environment, which limits their delivery and photosensitising efficiency.
      Liposomal delivery of photosensitisers will often overcome or decrease these
      problems. In addition, as with chemotherapeutic agents, liposomal formulations of
      photo-sensitising agents may help to achieve better selectivity for tumour tissue
      compared with normal tissue. Over the past years, liposomal photosensitisers have
      emerged as therapeutic agents in many experimental studies, and have obtained
      approval for clinical applications. Recent progress in liposomal technology
      further opens up the possibility of generating more selectively targeted
      photosensitisers encapsulated in liposomes. This review will cover progress in
      the use of liposomal photosensitisers, summarise current liposomal formulations,
      and project future directions for the liposomal delivery of photosensitising
      agents.

PMID- 16296770
TI  - Organogels in drug delivery.
AB  - In the last decade, interest in physical organogels has grown rapidly with the
      discovery and synthesis of a very large number of diverse molecules, which can
      gel organic solvents at low concentrations. The gelator molecules immobilise
      large volumes of liquid following their self-assembly into a variety of
      aggregates such as rods, tubules, fibres and platelets. The many interesting
      properties of these gels, such as their thermoreversibility, have led to much
      excitement over their industrial applications. However, only a few organogels are
      currently being studied as drug/vaccine delivery vehicles as most of the existing
      organogels are composed of pharmaceutically unacceptable organic liquids and/or
      unacceptable/untested gelators. In this paper a brief overview of organogels is
      presented, followed by a more in-depth review of the gels that have been
      investigated for drug and/or vaccine delivery. These include microemulsion-based
      gels and lecithin gels (studied for transdermal delivery), sorbitan monostearate
      organogels and amphiphilogels (studied as vaccine adjuvants and for oral and
      transdermal drug delivery, respectively), gels composed of alanine derivatives
      (investigated as in situ forming gels) and Eudragit organogels (studied as a
      matrix for suppositories). Finally, pluronic lecithin organogels, descendents of
      lecithin gels but which are not really organogels, are briefly discussed for
      their interesting history, their root and the wide interest in these systems.

PMID- 16296771
TI  - Buccal drug delivery.
AB  - Buccal formulations have been developed to allow prolonged localised therapy and
      enhanced systemic delivery. The buccal mucosa, however, while avoiding first-pass
      effects, is a formidable barrier to drug absorption, especially for
      biopharmaceutical products (proteins and oligonucleotides) arising from the
      recent advances in genomics and proteomics. The buccal route is typically used
      for extended drug delivery, so formulations that can be attached to the buccal
      mucosa are favoured. The bioadhesive polymers used in buccal drug delivery to
      retain a formulation are typically hydrophilic macro-molecules containing
      numerous hydrogen bonding groups. Newer second-generation bioadhesives have been
      developed and these include modified or new polymers that allow enhanced adhesion
      and/or drug delivery, in addition to site-specific ligands such as lectins. Over
      the last 20 years a wide range of formulations has been developed for buccal drug
      delivery (tablet, patch, liquids and semisolids) but comparatively few have found
      their way onto the market. Currently, this route is restricted to the delivery of
      a limited number of small lipophilic molecules that readily cross the buccal
      mucosa. However, this route could become a significant means for the delivery of
      a range of active agents in the coming years, if the barriers to buccal drug
      delivery are overcome. In particular, patient acceptability and the successful
      systemic delivery of large molecules (proteins, oligonucleotides and
      polysaccharides) via this route remains both a significant opportunity and
      challenge, and new/improved technologies may be required to address these.

PMID- 16296772
TI  - Pharmacokinetic/pharmacodynamic evaluation of inhalation drugs: application to
      targeted pulmonary delivery systems.
AB  - Inhaled therapy with either glucocorticoids and/or beta(2)-adrenergic drugs
      remains the mainstay of asthma treatment. In the last few years, a number of new
      products have been introduced into the market with the goal of improving efficacy
      and safety. This review article summarises the pharmacokinetic and
      pharmacodynamic properties of inhaled drugs for topical delivery necessary to
      achieve this goal. Pharmacokinetic properties include a high pulmonary
      deposition, low oral bioavailability, optimised pulmonary residence time and a
      very high systemic clearance. Optimisation of pharmacodynamic properties, such as
      receptor selectivity, may also yield drugs with improved pulmonary selectivity.
      As existing drugs also provide high efficacy and safety profiles, future
      developments will represent only slight improvements and quantum leap
      improvements are unlikely to occur.

PMID- 16296773
TI  - Emerging strategies for the transdermal delivery of peptide and protein drugs.
AB  - Transdermal delivery has been at the forefront of research addressing the
      development of non-invasive methods for the systemic administration of peptide
      and protein therapeutics generated by the biotechnology revolution. Numerous
      approaches have been suggested for overcoming the skin's formidable barrier
      function; whereas certain strategies simply act on the drug formulation or
      transiently increase the skin permeability, others are designed to bypass or even
      remove the outermost skin layer. This article reviews the technologies currently
      under investigation, ranging from those in their early-stage of development, such
      as laser-assisted delivery to others, where feasibility has already been
      demonstrated, such as microneedle systems, and finally more mature techniques
      that have already led to commercialisation (e.g., velocity-based technologies).
      The principles, mechanisms involved, potential applications, limitations and
      safety considerations are discussed for each approach, and the most advanced
      devices in each field are described.

PMID- 16296774
TI  - Delivery of Chlamydia vaccines.
AB  - The plethora of ocular, genital and respiratory diseases of Chlamydia, including
      nongonococcal urethritis, cervicitis pelvic inflammatory disease, ectopic
      pregnancy, tubal factor infertility, conjunctivitis, blinding trachoma and
      interstitial pneumonia, and chronic diseases that may include atherosclerosis,
      multiple sclerosis, adult onset asthma and Alzheimer's disease, still pose a
      considerable public health challenge to many nations. Although antibiotics are
      effective against Chlamydia when effectively diagnosed, asymptomatic infections
      are rampart, making clinical presentation of complications often the first
      evidence of an infection. Consequently, the current medical opinion is that an
      effective prophylactic vaccine would constitute the best approach to protect the
      human population from the most severe consequences of these infections. Clinical
      and experimental studies have demonstration that Chlamydia immunity in animals
      and humans is mediated by T cells and a complementary antibody response, and the
      completion of the genome sequencing of several isolates of Chlamydia is
      broadening our knowledge of the immunogenic antigens with potential vaccine
      value. Thus, major advances have been made in defining the essential elements of
      a potentially effective subunit vaccine design and parameters for evaluation.
      However, the challenge to develop effective delivery systems and human compatible
      adjuvants that would boost the immune response to achieve long-lasting protective
      immunity remains an elusive objective in chlamydial vaccine research. In response
      to evolving molecular and cellular technologies and novel vaccinology approaches,
      considerable progress is being made in the construction of novel delivery
      systems, such as DNA and plasmid expression systems, viral vectors, living and
      nonliving bacterial delivery systems, the use of chemical adjuvants, lipoprotein
      constructs and the codelivery of vaccines and specific immuno-modulatory
      biological agonists targeting receptors for chemokines, Toll-like receptors, and
      costimulatory molecules. The application of these novel delivery strategies to
      Chlamydia vaccine design could culminate in timely achievement of an efficacious
      vaccine.

PMID- 16296775
TI  - Nicotine delivery systems.
AB  - Over the past 20 years, medicinal nicotine has been used to aid smoking
      cessation, and has led to a significant increase in the number of smokers who
      successfully quit. This review describes currently available medicinal nicotine
      products, which include nicotine patch, gum, lozenge, nasal spray, inhaler and
      sublingual tablet, including their pharmacokinetics and recommended dosing. New
      developments in nicotine delivery that could further increase cessation rates
      include high-dose patches, rapid release gum, combined patch and acute forms, and
      several novel channels for nicotine delivery, such as nicotine drink, straw,
      lollipop and a pulmonary inhaler. New applications of existing and novel
      medicinal nicotine products may include relapse prevention, nicotine maintenance,
      temporary withdrawal management, reduced smoking and gradual quitting.

PMID- 16296776
TI  - Highly reproducible powder aerosolisation for lung delivery using powder-specific
      electromechanical vibration.
AB  - Dry powder inhalers (DPIs) have been in use since the 1970s, but it is only
      within the past few years that their use has constituted > approximately 10% of
      the inhaler units sold worldwide. Similarly, active DPIs have been in development
      for more than a decade, but no active device has yet been approved. Oriel is
      developing an active DPI technology that uses a very simple physical design
      coupled with a complex knowledge of powder flow and dispersion characterisation.
      The DPI uses electromechanical vibration with frequencies determined through the
      analysis of powder flow properties. Results so far have shown highly
      reproducible, efficient performance. The technology lends itself to both unit
      dose and multidose platforms in a targeted cost-effective DPI.

PMID- 16296777
TI  - TIMERx: novel polysaccharide composites for controlled/programmed release of
      drugs in the gastrointestinal tract.
AB  - Over the last 100 years tablets have grown from first invention to becoming the
      world's leading medicinal form, by any measure. This article considers some of
      the reasons for the pre-eminence of pharmaceutical tablets. Particular attention
      has been given to the role of controlled-release tablets and to a very versatile
      hydrogel-based controlled-release technology, called TIMERx((R)). The unique
      nature of TIMERx intermolecular physical chemistry is described in relation to
      the technology's potential to provide any one of a number of different release
      profiles, ranging from zero order to chronotherapeutic release. The unusual
      nature of TIMERx technology lies in its ability to provide different release
      kinetics by the manipulation of molecular interactions. This 'molecular engine'
      replaces the need for complex processing or novel excipients and allows desired
      drug release profiles to be 'factory set' following a simple formulation
      development process. The article describes the physico-chemical interactions of
      TIMERx technology at a molecular level and how they can be manipulated by
      formulation considerations. The article describes how TIMERx technology has been
      developed to the point where today it underpins a number of marketed
      pharmaceutical CR products as well as products under development by Penwest
      Pharmaceuticals.

PMID- 16296778
TI  - The XIIth International Symposium on Recent Advances in Drug Delivery Systems.
AB  - The XIIth International Symposium on Recent Advances in Drug Delivery Systems was
      held from 21-24 February 2005 in Salt Lake City, UT, USA. Approximately 250
      people attended this symposium dedicated to a broad variety of topics, ranging
      from recent advances in drug delivery systems to biomaterials and novel concepts
      in macromolecular therapeutics. A total of 33 people, all recognised specialists
      in the aforementioned fields, presented 30-min up-to-date reviews of these
      topics, as well as discussing recent results. In addition, the symposium included
      a poster session with approximately 100 displays highlighting various interesting
      data.

PMID- 16296779
TI  - Microparticles for oral delivery of vaccines.
AB  - Nonreplicating antigens are poorly immunogenic when given orally, either due to
      their degradation in the gastrointestinal tract or because they are not
      efficiently taken up in the gut. Studies in laboratory animals have clearly
      demonstrated that microparticles can significantly improve the immunogenicity of
      orally administered antigens. However, the oral delivery of vaccines using
      microparticles has not been explored extensively in humans and large animals. In
      this article the progress in oral microparticle antigen delivery will be reviewed
      and, where possible, studies in humans and large animals will be highlighted. In
      addition, possible approaches that have the potential to significantly improve
      microparticle delivery of oral vaccines will be suggested.

PMID- 16296780
TI  - Starch microparticles as vaccine adjuvant.
AB  - The demand for new vaccine adjuvants is well documented. New purified antigens
      from parasites, bacterial or viral pathogens, as well as recombinant subunit
      antigens and synthetic peptides, are often inherently weak immunogens; therefore,
      they need some kind of adjuvant to help initiate an immune response. In addition,
      there are very few adjuvants using the potential of the mucosal immune system,
      which may play an important role in the defence against air- and food-borne
      infections. Starch is a natural biocompatible and biodegradable polymer that is
      suitable for the production of various particulate adjuvant formulations, which
      can induce mucosal as well as systemic immune responses. This review gives an
      account of the different starch adjuvants used in immunisation studies. In
      particular, the properties of polyacryl starch microparticles as an oral vaccine
      adjuvant that induce protective immune responses in mice challenge experiments
      are summarised. In addition, a diphtheria booster vaccine has been proposed to be
      used to proving the concept in man and the possibilities to design an efficient
      vaccine formulation for human use are discussed.

PMID- 16296782
TI  - The potential of chitosan for the oral administration of peptides.
AB  - Over recent years, a major challenge in drug delivery has been the design of
      appropriate vehicles for the oral administration of macromolecular drugs
      (peptides and proteins). Indeed, despite the increasing market value of these
      complex molecules, their clinical use has been highly limited by their reduced
      oral bioavailability. Among the different delivery approaches explored so far,
      those based on the use of the polysaccharide chitosan have opened promising
      alternatives towards this ambitious goal. This is due to the interesting
      physicochemical and biopharmaceutical properties of this polymer. This article
      describes the advances that have been made in the design of chitosan-based
      systems specially adapted for the oral administration of peptides. These systems
      include solutions, microspheres, nanoparticles, nanocapsules and liposomes. More
      specifically, this article discusses the efficacy of the different delivery
      approaches for improving the absorption of peptides, and analyses the various
      mechanisms that have been proposed for the understanding of their efficacy.

PMID- 16296781
TI  - Strategies for DNA vaccine delivery.
AB  - Strategies for gene delivery comprise a diverse range of live and synthetic
      approaches; DNA delivery for the purposes of immunisation in turn comprises a
      large part of this research. This review mainly discusses synthetic systems for
      application in the delivery of plasmid DNA vaccines, outlining polylactide-co
      glycolide, liposome, chitosan and complex combination delivery systems. Areas of
      promise for DNA vaccine candidates include immune modulation of allergic
      responses and veterinarian application. The potential for realistic consideration
      of DNA vaccines as an alternative to existing approaches is dependent on the
      development of efficient DNA vaccine vectors and improved systems for DNA vaccine
      delivery. DNA vaccine technology may yet prove to be an important asset in an
      environment where there is a critical need for therapeutic and prophylactic
      strategies to combat a wide range of disease states.

PMID- 16296783
TI  - Oral pulsatile drug delivery systems.
AB  - In the field of modified release, there has been a growing interest in pulsatile
      delivery, which generally refers to the liberation of drugs following a
      programmable lag phase from the time of administration. In particular, the recent
      literature reports on a variety of pulsatile release systems intended for the
      oral route, which have been recognised as potentially beneficial to the
      chronotherapy of widespread diseases, such as bronchial asthma or angina
      pectoris, with mainly night or early morning symptoms. In addition, time
      dependent colon delivery may also represent an appealing related application. The
      delayed liberation of orally administered drugs has been achieved through a range
      of formulation approaches, including single- or multiple-unit systems provided
      with release-controlling coatings, capsular devices and osmotic pumps. Based on
      these premises, the aim of this review is to outline the rational and prominent
      design strategies behind oral pulsatile delivery.

PMID- 16296784
TI  - Antibody-cytotoxic agent conjugates for cancer therapy.
AB  - Antibody-based delivery of cytotoxic agents, including toxins, to tumours can
      dramatically reduce systemic toxicity and increase therapeutic efficacy. The
      advantage of a monoclonal antibody (mAb) is superior selectivity towards antigens
      expressed on the surface of cancer cells. Recent advances in biotechnology
      accelerated progress in the pharmaceutical applications of mAbs. A cytotoxic
      warhead is attached to a mAb in an immunoconjugate via a linker, which is stable
      in circulation but efficiently cleaved in the tumour tissue. The warhead, mAb and
      linker play important roles in the successful design of potent and efficient
      immunoconjugates. To date, one mAb-cytotoxic agent conjugate has been approved by
      the FDA and several other candidates are in various stages of clinical trials.
      This review describes the recent progress in the design and development of mAb
      based immunoconjugates of cytotoxic agents, and summarises the criteria for the
      critical choices of a suitable mAb, linker and cytotoxic agent to design an
      efficacious immunoconjugate.

PMID- 16296785
TI  - Ophthalmic drug delivery considerations at the cellular level: drug-metabolising
      enzymes and transporters.
AB  - Ophthalmic drugs typically achieve < 10% ocular bioavailability. A drug applied
      to the surface of the eye may cross ocular-blood barriers where it may encounter
      metabolising enzymes and cellular transporters before it distributes to the site
      of action. Characterisation of ocular enzyme systems and cellular transporters
      and their respective substrate selectivity have provided new insight into the
      roles these proteins may play in ocular drug delivery and distribution. Altered
      metabolism and transport have been proposed to contribute to a number of ocular
      disease processes including inflammation, glaucoma, cataract, dry eye and
      neurodegeneration. As ocular enzyme and transport systems are better
      characterised, their properties become an integral consideration in drug design
      and development.

PMID- 16296786
TI  - Biomedical aspects of targeted delivery of drugs to pulmonary endothelium.
AB  - Drug targeting to selected subcellular compartments of the pulmonary endothelium
      may optimise treatment of many diseases. This paper describes endothelial
      determinants that are potentially useful for such targeting, including
      endothelial ectopeptidases, cell adhesion molecules and novel candidates
      identified by high-throughput methods, as well as the means to achieve optimal
      subcellular targeting of drugs in the endothelium that have been explored in cell
      culture and animal studies. Criteria for determining the applicability for
      targeting include accessibility, specificity, safety and subcellular precision.
      The effects of endothelial delivery of therapeutic agents, including the effects
      mediated by the intervention in the function of the target determinants, must be
      characterised in the context of given pathological conditions.

PMID- 16296787
TI  - The MediChew technology platform.
AB  - A few decades ago, chewing gum was rarely considered when industry searched for
      an applicable delivery vehicle for an active pharmaceutical substance. Yet, the
      1980s and 1990s saw gum become the most successful nicotine delivery form;
      unawareness changed to cautious scepticism, and today the merits of chewing gum
      drug delivery technologies are generally appreciated. MediChew is the registered
      trademark of Fertin Pharma's medical chewing gum technology platform. Based on
      patent-protected technologies, it offers unique taste-masking possibilities and
      allows control of drug molecule release. Medical chewing gum products based on
      these technologies are specifically suitable for convenient administration on
      demand, for active substances providing a topical effect in the oral cavity and
      throat, and for systemic delivery of drug molecules that readily cross the
      oromucosal membranes.

PMID- 16296789
TI  - Towards screening of inhalation formulations: measuring interactions with atomic
      force microscopy.
AB  - This review charts the progress of atomic force microscopy (AFM) to investigate
      particle interactions relevant to the performance of inhalers. AFM provides a
      unique opportunity to examine and quantify single particle behaviour of powdered
      drugs and excipients in a variety of environmental conditions. An introduction to
      AFM and particle interactions is given. Comparative experiments that rank
      adhesion between materials, and quantitative experiments that lead to the
      measurement of properties such as the work of adhesion and surface energy, are
      reviewed. The AFM has been widely used to investigate the effects of relative
      humidity and surface roughness on particle adhesion; these experiments are also
      reviewed. In the final section, the potential of this approach to screen
      formulations is discussed.

PMID- 16296790
TI  - Novel hydrofluoroalkane suspension formulations for respiratory drug delivery.
AB  - Due to the poor solvent properties of hydrofluoroalkanes, suspension is often the
      only formulation option for respiratory drug delivery. Research in this area has
      focussed mainly on two main themes over the past 5 years: new design of
      stabilisers and particle engineering. Among the most important advances, the
      introduction of secondary particulate systems and the establishment of porous
      particles as a viable delivery system must be mentioned. Other noteworthy
      developments include new classes of stabilisers and surface tailoring approaches.
      Work has been underpinned by new theoretical insights, via the introduction of
      atomic force microscopy to measure particle interactions, and the development of
      the surface tension component approach to predict them. Future areas of
      development include the formulation of nanoparticles and of non-inhalation
      therapies in non-pressurised hydrofluoroalkanes. All these aspects are reviewed
      in this article.

PMID- 16296788
TI  - Pharmaceutical development and clinical effectiveness of a novel gel technology
      for transdermal drug delivery.
AB  - Transdermal gels are designed to deliver sustained drug amounts, resulting in
      systemically consistent levels. They represent an improvement compared with
      transdermal delivery by patches because they offer more dosage flexibility, less
      irritation potential and a better cosmetic appearance. Advanced Transdermal
      Delivery (ATD) gel technology was developed in order to provide enhanced passive
      skin permeation of various active drugs for the treatment of many conditions,
      including hypogonadism, female sexual dysfunction, postmenopausal symptoms,
      overactive bladder and anxiety. The technology consists of a combination of
      solvent systems and permeation enhancers enabling systemic drug delivery, and is
      covered by many patents. Pharmaceutical development of formulations based on the
      technology allowed optimisation of physicochemical parameters (rheological
      profile, pH) as well as skin permeation properties (type and concentration of
      permeation enhancers, thermodynamic activity of the drug). This gel technology
      has demonstrated to be efficient for many drugs, as shown in the preclinical and
      clinical pharmacokinetic studies presented in this technology evaluation.

PMID- 16296791
TI  - On the delivery of small interfering RNAs into mammalian cells.
AB  - RNA interference is becoming the technique of choice for analysing gene function
      and drug target validation. In this process, sequence-specific gene inhibition is
      initiated by small RNA duplexes, known as small interfering RNAs (siRNAs). The
      possibility that exogenously delivered siRNAs or endogenously expressed hairpin
      siRNAs can cause the destruction of specific target mRNA in vitro and in animal
      models has been demonstrated. However, the key challenges for the development of
      siRNAs as human therapeutics is largely dependent on the development of suitable
      delivery agents and improved siRNA specificity. This review highlights recent
      advances in siRNA delivery, as well as challenging problems related to immune
      stimulation.

PMID- 16296792
TI  - Stimulus-controlled delivery of drugs and genes.
AB  - Macromolecular and colloidal systems used for the systemic delivery of drugs and
      genes promise to improve the way we treat and prevent numerous diseases. New
      generations of drug and gene delivery systems (DGDS) are being designed to
      enhance further efficiency by using a range of endogenous and external stimuli.
      This review focuses on three qualitatively distinct ways a stimulus can improve
      the efficiency of DGDS; namely, by selectively triggering release of the
      therapeutic agent from the DGDS, by modulating physical properties of DGDS and by
      favourably altering physiological properties of tissues to enhance DGDS
      transport. Recent developments in these areas are discussed to illustrate the
      potential of stimulus-controlled DGDS in the development of new generations of
      therapeutics.

PMID- 16296794
TI  - Role of efflux pumps and metabolising enzymes in drug delivery.
AB  - The impact of efflux pumps and metabolic enzymes on the therapeutic activity of
      various drugs has been well established. The presence of efflux pumps on various
      tissues and tumours has been shown to regulate the intracellular concentration
      needed to achieve therapeutic activity. The notable members of efflux proteins
      include P-glycoprotein, multi-drug resistance protein and breast cancer
      resistance protein. These efflux pumps play a pivotal role not only in extruding
      xenobiotics but also in maintaining the body's homeostasis by their ubiquitous
      presence and ability to coordinate among themselves. In this review, the role of
      efflux pumps in drug delivery and the importance of their tissue distribution is
      discussed in detail. To improve pharmacokinetic parameters of substrates, various
      strategies that modulate the activity of efflux proteins are also described. Drug
      metabolising enzymes mainly include the cytochrome P450 family of enzymes.
      Extensive drug metabolism due to the this family of enzymes is the leading cause
      of therapeutic inactivity. Therefore, the role of metabolising enzymes in drug
      delivery and disposition is extensively discussed in this review. The synergistic
      relationship between metabolising enzymes and efflux proteins is also described
      in detail. In summary, this review emphasises the urgent need to make changes in
      drug discovery and drug delivery as efflux pumps and metabolising enzymes play an
      important role in drug delivery and disposition.

PMID- 16296793
TI  - Chronopharmacology and controlled drug release.
AB  - Circadian rhythms in the body are well established and are an important factor to
      consider when administering drugs. Many diseases display symptoms and onset
      characteristics that are not randomly distributed within 24 h (e.g., coronary
      infarction, angina pectoris, asthmatic attacks and peptic ulcer perforations);
      therefore, it is not surprising that the effects and/or pharmacokinetics of drugs
      can display significant daily variations. Recent data, primarily concerned with
      the chronopharmacokinetics of antiasthmatics, histamine H2-blockers and
      cardiovascular active drugs (e.g., propanolol, organic nitrate and nifedipine)
      are described as representative examples in this review. The data demonstrate
      that biological rhythms should have been taken into account when evaluating drug
      delivery systems, galenic formulations and pharmacokinetics as a basis for drug
      treatment.

PMID- 16296795
TI  - Novel delivery methods for treatment of viral hepatitis: an update.
AB  - Viral hepatitis represents the most common cause of chronic liver disease
      worldwide. Currently approved therapies for chronic hepatitis B include IFN, an
      immune modulator, and nucleoside analogues lamivudine and adefovir. For chronic
      hepatitis C, a combination of pegylated IFN-alpha and ribavirin represents the
      standard treatment. However, currently available treatments for both these
      viruses are effective only in a limited number of patients, are costly,
      prolonged, associated with significant side effects and require a substantial
      commitment from the patients and healthcare providers. A number of novel
      antiviral treatments, together with strategies to enhance the response to current
      therapies, are being explored at present. For all new therapies, as well as for
      improving existing treatments, selective delivery of medications into liver cells
      would be desirable to enhance antiviral activity and avoid systemic side effects.
      New achievements in the field of drug and gene delivery against chronic hepatitis
      to the liver are reviewed here.

PMID- 16296796
TI  - Delivery of plant-derived vaccines.
AB  - Many protein subunit vaccine candidates have been expressed in transgenic plants,
      and in a few cases the recombinant material has entered early phase clinical or
      target animal trials. The expressed protein can be purified prior to formulation
      for any preferred delivery approach. However, there are major cost advantages
      associated with avoiding protein purification and pursuing the oral delivery of a
      processed plant product containing the recombinant protein. Grains and dry
      products that are processed from fresh plant tissues can stably store expressed
      proteins for extended periods of time at room temperature, making refridgeration
      unnecessary during storage and distribution. Encapsulation of recombinant
      proteins in plant tissues guards against their rapid degradation in the gut,
      therefore facilitating the uptake and induction of appropriate immune responses.
      Early trial data with plant-based vaccine candidates has shown promising safety
      and efficacy.

PMID- 16296797
TI  - Vaginal delivery of contraceptives.
AB  - Although a steady increase in contraceptive use has been observed both in
      developed and less-developed countries, the large number of unplanned pregnancies
      may indicate that the contraceptive needs of a significant percentage of couples
      have so far not been met. Several new contraceptive products have reached the
      market during the last 2 years. Among these is a new contraceptive vaginal ring,
      which has become available for prescription. This new female method has been
      developed to expand the contraceptive choices available to couples. This review
      will address the specifics of the vaginal route for delivering contraceptive
      steroids and describe the various systems available or under evaluation.

PMID- 16296799
TI  - Supercritical fluid technology for enhanced drug delivery.
AB  - The rapid advances in the development of formulation and delivery systems based
      on micron-sized and nanoscale drug particles will create significant benefits to
      the pharmaceutical industry. Complementary to traditional methods, supercritical
      fluid techniques have found many useful, and sometimes unique, applications in
      the production and processing of drug particles. In this article background
      information is provided on a variety of supercritical fluid techniques relevant
      to drug formulation and delivery, recent advances and novel applications are
      highlighted, and the successful development of a new supercritical fluid rapid
      expansion technique for producing exclusively nanoscale drug particles will be
      discussed. Challenges and opportunities for further development and future
      applications are also reviewed.

PMID- 16296798
TI  - Delivery of therapeutic proteins to the mucosa using genetically modified
      microflora.
AB  - Drug delivery through mucosal surfaces offers a panorama of opportunities. The
      advantages are clear and include safety, ease of administration and higher social
      acceptance, although the major disadvantages are drug availability and
      appropriate drug targeting. Most mucosa are well equipped to manage the presence
      of bacteria and many are actually permanently colonised with a specific
      microflora. Such microbiota may become attractive tools for the delivery of a
      specific niche of protein therapeutics. These proteins can be produced from
      genetically modified microbes that are common to the mucosa, and their delivery
      to the host tissues has been demonstrated. This concept is being developed for
      the delivery of proteins to the intestine, but has also been applied in delivery
      to the vagina, nose and mouth.

PMID- 16296800
TI  - Controlled inhalation of aerosolised therapeutics.
AB  - With the advent of new, and often expensive, therapeutics designed for aerosol
      delivery to the lung, there is a need to improve the targeting and efficiency of
      their delivery. By controlling breathing patterns associated with inhaled
      aerosols, it has been shown that deposition in the lung can be both maximised and
      targeted to specific lung regions. A new commercially available device, the AKITA
      (Inamed GmbH) allows for individualised, controlled inhalation of aerosols
      produced by conventional nebulisers. Smart card technology is incorporated into
      the AKITA to both individualise breathing patterns as well as record compliance
      of therapy. So far, the use of this new device has provided maximal delivery of
      drug to the lung, with improved patient compliance and minimal waste of drug.

PMID- 16296801
TI  - Advancing vaginal drug delivery.
AB  - Bacterial vaginosis and vulvovaginal candidiasis are the two most common forms of
      vaginitis in female patients. Although a variety of effective treatments have
      been available to eradicate these infections, limitations have lessened the
      utility of previously available products. Oral therapies are often fraught with
      systemic adverse reactions, as well as the potential to interact with concomitant
      medications. Vaginal preparations, although generally perceived as safer, have
      historically been undesirable for women to use due to their multiple days of
      dosing; messy, dripping creams; and requisite night-time dosing. Recognising that
      the therapeutic delivery of the active agent plays a critical role in the overall
      success of therapy, and attempting to circumvent the weaknesses of traditional
      vaginal drug delivery while maintaining and even improving safety profiles, a new
      form of vaginal drug delivery was developed. This unique and proprietary delivery
      system, with both bioadhesive and sustained release properties, introduces the
      convenience of a single dose of medication that can be applied at any time, with
      efficacy rates equivalent to lengthier durations of treatment. This advance in
      science and technology has now been successfully applied to two products,
      Gynazole-1(butoconazole nitrate 2%) and Clindesse(clindamycin phosphate 2%)
      indicated for the treatment of vulvovaginal candidiasis and bacterial vaginosis,
      respectively, in order to enhance convenience and compliance for the treatment of
      two very common clinical conditions.

PMID- 16296802
TI  - Paediatric pulmonary drug delivery: considerations in asthma treatment.
AB  - Aerosol therapy, the preferred route of administration for glucocorticosteroids
      and short-acting beta(2)-adrenergic agonists in the treatment of paediatric
      asthma, may be given via nebulisers, metered-dose inhalers and dry powder
      inhalers. For glucocorticosteroids, therapy with aerosolised medication results
      in higher concentrations of drug at the target organ with minimal systemic side
      effects compared with oral treatments. The dose of drug that reaches the airways
      in children with asthma is dependent on both the delivery device and patient
      related factors. Factors that affect aerosol drug delivery are reviewed briefly.
      Advantages and disadvantages of each device and device-specific factors that
      influence patient preferences are examined. Although age-based device
      recommendations have been made, the optimal choice for drug delivery is the one
      that the patient or caregiver prefers to use, can use correctly and is most
      likely to use consistently.

PMID- 16296803
TI  - Radiotargeting agents for cancer therapy.
AB  - Although the general radiobiological principles underlying external beam therapy
      and radionuclide therapy are the same, there are significant differences in the
      radiobiological effects observed in mammalian cells. In external beam therapy and
      brachytherapy, emissions are composed of photons, whereas in radionuclide
      therapy, the radiations of interest are particulate. This article will explore
      the special features that characterise the biological effects consequent to the
      traversal of charged particles through mammalian cells. In addition, it will
      highlight what has been learned when these radionuclides and targeting
      radiopharmaceuticals are used to treat cancers.

PMID- 16296804
TI  - Delivery of parathyroid hormone for the treatment of osteoporosis.
AB  - Parathyroid hormone (PTH), along with its fragments and analogues, potently
      restores bone mass and biomechanical strength in animal models of osteoporosis,
      and reduces fractures by up to 65% in clinical trials in osteoporotic patients.
      Despite this demonstrated efficacy, patient acceptance and compliance with PTH is
      limited by the need for daily subcutaneous injections. The development of an
      equally efficacious, noninjectable form of PTH would significantly expand the
      present market. A challenge to the development of an alternative delivery system
      is the requirement for low-dose, daily, intermittent pulses of PTH to induce the
      anabolic actions on bone. In this review, recent basic and clinical efforts to
      deliver PTH by oral, buccal, sublingual, transdermal, nasal and pulmonary
      approaches will be addressed.

PMID- 16296805
TI  - Intelligent hydrogels for the oral delivery of chemotherapeutics.
AB  - A novel approach toward improvements of oral chemotherapeutic formulations has
      evolved, which combines solubilisation (molecular dispersion) of the hydrophobic
      anticancer drugs in micelles attached to large macromolecules or microparticles.
      The large size of the macromolecules or microgels prevents the gel components
      from being transported into the systemic circulation. The discussed gels comprise
      copolymers of poly(acrylic acid) (PAA) and Pluronic surfactants, linked via C-C
      bonds. The Pluronic-PAA copolymers are non-irritating when administered orally.
      The micelles formed in the Pluronic-PAA solutions and in crosslinked microgels
      can be loaded with chemotherapeutic drugs and then released in contact with the
      intestine. The microgels are collapsed at the acidic pH of the stomach and
      expand, thus releasing the loaded drugs at the pH of the lower gastrointestinal
      tract. Yet the microgels are mucoadhesive and enable longer retention time and
      prolonged release in the colon. Ease of preparation and formulation of the drugs
      with the Pluronic-PAA polymers and gels may enable the wider use of oral
      chemotherapy, resulting in a better patient compliance and improved quality of
      life of the patients.

PMID- 16296807
TI  - Factors of importance for a successful delivery system for proteins.
AB  - Protein pharmaceuticals have matured into an important class of drugs, now
      comprising one in three novel drugs introduced on the market. However,
      significant gains are still to be made in reducing the costs of production,
      ensuring proper pharmacokinetics and efficacy, increasing patient compliance and
      convenience, and reducing side effects such as immunogenicity. This review
      summarises these issues and provides recent examples of methods to reduce costs,
      alter pharmacokinetics and increase patient compliance. It also discusses the
      increasing interest in understanding immunogenicity in order to prevent failure
      of the protein drug or serious life-threatening side effects due to
      autoimmunogenicity.

PMID- 16296806
TI  - Drug delivery strategies for cathepsin inhibitors in joint diseases.
AB  - Cathepsins play important roles in the development of joint and bone diseases
      such as osteoporosis, rheumatoid arthritis (RA) and osteoarthritis (OA).
      Cathepsin inhibitors are presently in development and clinical testing for use as
      novel disease-modifying drugs for the improved treatment of osteoporosis. They
      may also be applicable for the treatment of joint diseases. However, some
      barriers still hamper their clinical applications in these indications. Based on
      pathophysiological features of RA and OA, the authors discuss six potential drug
      delivery strategies for the effective delivery of cathepsin inhibitors or other
      antiarthritic drugs to the arthritic joint tissue. Successful application of
      these strategies may significantly contribute to a more effective and safe
      treatment of RA and OA.

PMID- 16296808
TI  - Current advances in sustained-release systems for parenteral drug delivery.
AB  - Major progresses in the development of parenteral sustained-release systems have
      been made in recent years as evidenced by the regulatory approval and market
      launch of several new products. Both the availability of novel carrier materials
      and the advances in method of fabrication have contributed to these commercial
      successes. With the formulation challenges associated with biologics, new
      delivery systems have also been evolved specifically to address the unmet needs
      in the parenteral sustained release of proteins. In this review paper, different
      new carriers systems and preparation methods are discussed with special focus on
      their applications to biologicals.

PMID- 16296809
TI  - Advances in the delivery of treatments for Parkinson's disease.
AB  - Innovative drug delivery in Parkinson's disease (PD) has the potential to reduce
      or avoid many side effects of current treatment, such as wearing-off type
      fluctuations, dyskinesia, on-off phenomena or bouts of motor freezing. The
      traditional orally administered formulations of l-dihydroxyphenylalanine combined
      with a peripheral aromatic acid decarboxylase inhibitor remain the mainstay of
      treatments for PD. However, such combination therapies have been further
      formulated to extend their duration of action by including a catechol-O
      methyltransferase inhibitor. Preventing the breakdown of dopamine has also been
      achieved by monoamine oxidase-B inhibition; this approach now having been
      formulated for sublingual use (Zelapar, Valeant Pharmaceuticals). An alternative
      approach bypasses the oral route of administration and instead relies on
      continuous duodenal infusion (Duodopa, Solvay, NeoPharma AB) for better
      therapeutic effect. The clinical use of dopamine agonists as antiparkinsonian
      drugs now incorporates a variety of delivery techniques. For example,
      apomorphine, which relies on parenteral administration for maximum
      bioavailability, may be delivered via rectal, intranasal, sublingual and
      subcutaneous (e.g., Apokyn, Mylan Bertek) routes. Meanwhile, rotigotine and
      lisuride have both been formulated for delivery via skin patches. Finally, the
      authors examine more experimental delivery techniques, including the delivery of
      genes via viral vectors or liposomes, intracranial transplant of a variety of
      cells and of L-dihydroxyphenylalanine by prodrug-dispensing liposomes or
      pulmonary delivery (AIR, Alkermes). The advent and application of these varied
      technologies will help encourage patient-specific means of treatment for PD.

PMID- 16296810
TI  - Antibodies as delivery vehicles for radioimmunotherapy of infectious diseases.
AB  - The field of infectious diseases is in crisis and there is a need for strategies
      that can facilitate the rapid development of new antimicrobial agents.
      Radioimmunotherapy (RIT), a therapeutic modality originally developed for cancer
      treatment, has recently been suggested as a novel therapy for the treatment of a
      variety of infectious diseases. Because specific antibodies are used in RIT as
      delivery vehicles of cytocidal radiation, their molecular weight influences the
      nonspecific accumulation in infectious foci and blood clearance, and their
      affinity-specific accumulation of antibodies in infectious foci. Like the
      problems encountered in oncology, relevant variables in the development of RIT of
      infectious diseases include target antigen-shedding; delivering radionuclides to
      infectious foci in organs, abscesses, granulomas, heart and brain, and potential
      safety concerns. Dadachova and Casadevall anticipate that RIT can be developed
      for many types of infectious diseases, including microbes resistant to
      conventional antimicrobial therapy and agents of biological warfare.

PMID- 16296811
TI  - Applications of biomimetic systems in drug delivery.
AB  - This review article highlights recent activities in the field of biomimetic
      systems and their application in controlled drug delivery. A definition and
      overview of biomimetic processes is given, with a focus on synthesis and assembly
      for the creation of novel biomaterials. In particular, systems are classified on
      the basis of three subsets, which include biological, biohybrid and synthetic
      structures. Examples focus on the current and proposed clinical significance for
      systems that mimic processes where the underlying molecular principles are well
      understood. Biomimetic materials and systems are presented as exceptional
      candidates for various controlled drug delivery applications and have enormous
      potential in medicine for the treatment of disease.

PMID- 16296812
TI  - Pulmonary insulin delivery by means of the Technosphere drug carrier mechanism.
AB  - Technosphere/Insulin (TI) is a formulation of regular human insulin designed for
      efficient transport across the respiratory epithelium into the circulation. The
      drug carrier mechanism achieves a fast systemic insulin uptake (maximum time
      approximately 15-20 min), a fast onset of action (maximum activity approximately
      25-30 min) and a short duration of action (approximately 2 h). Bioavailability,
      relative to subcutaneous injection, was established to be between 30 and 50% with
      a linear dose-response relationship and low variability. In all published short
      term studies, TI was well tolerated. Provided a reliable long-term safety
      profile, TI may become a suitable alternative to subcutaneous injection for
      prandial insulin delivery. TI offers the possibility of new treatment regimens,
      especially in patients with Type 2 diabetes.

PMID- 16296814
TI  - Stabilization of unsolvated europium and ytterbium pentafluorophenyls by pi
      bonding encapsulation through a sterically crowded triazenido ligand.
AB  - The one-pot transmetalation/deprotonation reaction of the bulky triazene
      Dmp(Tph)N3H with bis(pentafluorophenyl)mercury and europium or ytterbium affords
      the structurally characterized unsolvated metal(II) pentafluorophenyl triazenides
      [Dmp(Tph)N3MC6F5] (M = Eu, Yb; Dmp = 2,6-Mes2C6H3 with Mes = 2,4,6-Me3C6H2; Tph =
      2-TripC6H4 with Trip = 2,4,6-(i)Pr3C6H2) or, depending on the molar ratio, the
      solvated complex [Dmp(Tph)N3YbC6F5(THF)].

PMID- 16296813
TI  - Frosta: a new technology for making fast-melting tablets.
AB  - The fast-melting tablet (FMT) technology, which is known to be one of the most
      innovated methods in oral drug delivery systems, is a rapidly growing area of
      drug delivery. The initial success of the FMT formulation led to the development
      of various technologies. These technologies, however, still have some
      limitations. Recently, a new technology called Frosta (Akina) was developed for
      making FMTs. The Frosta technology utilises the conventional wet granulation
      process and tablet press for cost-effective production of tablets. The Frosta
      tablets are mechanically strong with friability of < 1% and are stable in
      accelerated stability conditions when packaged into a bottle container. They are
      robust enough to be packaged in multi-tablet vials. Conventional rotary tablet
      presses can be used for the production of the tablets and no other special
      instruments are required. Thus, the cost of making FMTs is lower than that of
      other existing technologies. Depending on the size, Frosta tablets can melt in <
      10 s after placing them in the oral cavity for easy swallowing. The Frosta
      technology is ideal for wide application of FMTs technology to various drug and
      nutritional formulations.

PMID- 16296815
TI  - Cleavage of X-H bonds (X = N, o, or C) by copper(I) alkyl complexes to form
      monomeric two-coordinate copper(I) systems.
AB  - The monomeric copper(I) alkyl complexes (IPr)Cu(R) [R = Me or Et; IPr = 1,3
      bis(2,6-diisopropylphenyl)imidazol-2-ylidene] react with substrates that possess
      N-H, O-H, and acidic C-H bonds to form monomeric systems of the type (IPr)Cu(X)
      (X = anilido, phenoxide, ethoxide, phenylacetylide, or N-pyrrolyl) and methane or
      ethane. Solid-state X-ray crystal structures of the anilido, ethoxide, and
      phenoxide complexes confirm that they are monomeric systems. Experimental studies
      on the reaction of (IPr)Cu(Me) and aniline to produce (IPr)Cu(NHPh) suggest that
      a likely reaction pathway is coordination of aniline to Cu(I) followed by proton
      transfer to produce methane and the copper(I) anilido complex.

PMID- 16296816
TI  - [(Triphos)Ni(eta2-BH4)]: an unusual nickel(I) borohydride complex.
AB  - Reduction of [(triphos)NiCl2] (1) with an excess of NaBH4 in THF produces the
      paramagnetic Ni(I) complex [(triphos)Ni(eta2-BH4)] (2). X-ray crystallography
      shows 1 to be a square-planar Ni(II) species in which the phosphine ligand is
      bidentate, whereas 2 has pseudotetrahedral geometry at the Ni(I) center, with a
      tridentate phosphine and the borohydride ligand occupying a single coordination
      site. Density functional theory calculations show the unpaired electron in 2 to
      reside in an orbital located mainly on the Ni atom.

PMID- 16296817
TI  - Synthesis and properties of Ph2S(=N-(Ph2)S[triple bond]N)2.
AB  - A new type of lambda6-sulfanenitrile with an SN triple bond at both ends, Ph2S(=N
      (Ph2)S[triple bond]N)2 (5), was prepared in excellent yield from the one-pot
      synthesis of diphenylsulfimide (Ph2SNH) with fluoro(diphenyl)-lambda6
      sulfanenitrile (Ph2FSN) in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene.
      Its molecular structure was determined by X-ray crystallographic analysis.
      Compound 5 reacted further with methyl triflate and trifluoromethanesulfonic
      anhydride to afford the corresponding bis-N-methylated and -N-sulfonated
      compounds.

PMID- 16296819
TI  - Single-molecule magnets: a reductive aggregation route to new types of Mn12
      complexes.
AB  - Three dodecanuclear Mn clusters [Mn12O10(OMe)3(OH)(O2CC6H3F2)16(MeOH)2].8MeOH
      (1), [Mn12O10(OMe)4(O2CBu(t))16(MeOH)2] (2), and [Mn12O12(O2CBu(t))16(MeOH)4] (3)
      synthesized by reductive aggregation reactions are reported. Clusters 1 and 2
      possess a central alkoxide-bridged planar Mn4 topology, whereas 3 is a new high
      symmetry member of the normal Mn12 family. Complexes 1 and 2 crystallize in the
      monoclinic space groups C2/c and P2(1)/n, respectively. Both consist of four
      Mn(IV) and eight Mn(III) ions held together by 10 mu3-O2- ions, and either (i)
      one mu-OH- and three mu-MeO- groups for 1 or (ii) four mu-MeO- groups for 2.
      Complex 3 crystallizes in the orthorhombic space group Aba2 and possesses the
      normal Mn12 structure but with terminal MeOH molecules. The cyclic voltammogram
      (CV) of 1 exhibits no reversible redox processes. Variable-temperature, solid
      state dc and ac magnetic susceptibility measurements on 1 and 2 reveal that they
      possess S = 5 and 9 ground states, respectively. In addition, ac susceptibility
      measurements on complex 1 in a zero dc field in the temperature range 1.8-10 K
      and in a 3.5 G ac field oscillating at frequencies in the 5-1488 Hz range display
      a nonzero frequency-dependent out-of-phase (chi(M)'') signal at temperatures
      below 3 K, with the peak maxima lying at temperatures below 1.8 K. For complex 2,
      two frequency dependent chi(M)'' signals are seen, one in the higher temperature
      range of 3-5 K and a second at lower temperatures with its peak maxima at
      temperatures below 1.8 K. Single-crystal magnetization vs dc field scans down to
      0.04 K for 1.8MeOH and 2 show hysteresis behavior at <1 K, confirming that both
      complexes are new examples of SMMs.

PMID- 16296818
TI  - Diiron(II) mu-aqua-mu-hydroxo model for non-heme iron sites in proteins.
AB  - We have synthesized a diiron(II) complex with a novel aqua-hydroxo bridging
      motif, [Fe2(mu-H2O)(mu-OH)(TPA)2](OTf)3 (1). This is a new member of the diiron
      diamond core family. The complex is stable in solution in nonpolar solvents as
      well as in the solid state. Two high-spin iron(II) sites are
      antiferromagnetically coupled (J = -9.6 cm(-1)). The drastic difference of ca. 1
      V in the redox potential between complex 1 and its bis(hydroxo)-bridged analogue
      Fe2(OH)2(TPA)3+ is accompanied by only a moderate difference in the dioxygen
      reactivity. This observation is consistent with the inner-sphere mechanism of
      iron(II)-dioxygen association rather than the outer-sphere electron transfer.

PMID- 16296820
TI  - Intermetallic compounds with near Zintl phase behavior: RE2Zn3Ge6 (RE = La, Ce,
      Pr, Nd) grown from liquid indium.
AB  - A series of compounds has been discovered while investigating reactions of rare
      earth, transition metals, and Ge in excess indium. These compounds, RE2Zn3Ge6 (RE
      = La, Ce, Pr, Nd), are isostructural, crystallizing in the orthorhombic space
      group Cmcm with lattice parameters a = 5.9691(9) angstroms, b = 24.987(4)
      angstroms, and c = 5.9575(9) angstroms for La2Zn3Ge6, a = 5.9503(5) angstroms, b
      = 24.761(2) angstroms, and c = 5.9477(5) angstroms for the Ce analogue, a
      =5.938(2) angstroms, b = 24.708(8) angstroms, and c = 5.936(2) angstroms for
      Pr2Zn3Ge6, and a = 5.9094(7) angstroms, b = 24.619(3) angstroms, and c =
      5.9063(5) angstroms for the Nd analogue. The structure is composed of PbO-like
      ZnGe layers and ZnGe4 cage layers and is related to the Ce4Zn8Ge(11-x) structure
      type. The bonding in the system can be rationalized using the Zintl concept
      resulting in a material that is expected to be a valence precise semiconductor,
      although its behavior is more consistent with it being a semimetal, making it an
      intermediate case. The results of band structure calculations and magnetic
      measurements of these compounds are discussed.

PMID- 16296821
TI  - Structure, bonding, and reactivity of Ti and Zr amidate complexes: DFT and X-ray
      crystallographic studies.
AB  - Easily prepared and highly modular organic amide proligands have been used to
      synthesize a series of new bis(amidate)-bis(amido) Ti and Zr complexes via
      protonolysis. These complexes have been structurally characterized by NMR
      spectroscopy and X-ray crystallography. The solid-state molecular structures of
      these complexes indicate that the amidate ligands bind to the metal centers in an
      exclusively bidentate fashion, resulting in discrete monomeric species. Geometric
      isomerism in these species is highly dependent upon the steric characteristics of
      the proligands utilized in the synthesis. In solution, these complexes are
      observed to isomerize on the NMR time scale, with one isomer being predominant.
      Bonding in the bis(amidate)-bis(amido) complexes was investigated by DFT
      calculations. The geometric isomers predicted by theory matched the
      experimentally observed results, within experimental error. The orbitals
      associated with amidate-metal bonding are energetically well below the frontier
      orbitals. The HOMO in these complexes is a pi orbital associated with amido
      ligand-to-metal bonding character, while the LUMO in all cases is a vacant d
      orbital on the metal center.

PMID- 16296822
TI  - Metal-enhanced H-bond donor tendencies of urea and thiourea toward anions:
      ditopic receptors for silver(I) salts.
AB  - The heteroditopic receptors 1 and 2 firmly include an Ag(I) ion into the NS2O2
      crown and establish selective H-bond interactions with anions at the covalently
      linked urea/thiourea (U/T) subunit. Studies in MeCN solution showed that the
      metal center induces a 10(3)-10(6)-fold enhancement of the anion association
      constant, due to a coordinative interaction with the O/S atom of the U/T moiety.
      In the presence of F-, the Ag-O interaction promotes the release of a proton from
      one of the urea N-H fragments. Ag(I) coordination to the S atom of the thiourea
      derivative 2 promotes the formation of unusually stable H-bond complexes with Cl-
      and Br-.

PMID- 16296823
TI  - The challenge of being straight: explaining the linearity of a low-spin [FeNO]7
      unit in a tropocoronand complex.
AB  - We have carried out a density functional theory study of the S = 1/2 [FeNO]7
      tropocoronand complex, Fe(5,5-TC)NO, as well as of some simplified models of this
      compound. The calculations accurately reproduce the experimentally observed
      trigonal-bipyramidal geometry of this complex, featuring a linear NO in an
      equatorial position and a very short Fe-N(NO) distance. Despite these unique
      structural features, the qualitative features of the bonding turn out to be
      rather similar for Fe(5,5-TC)NO and [FeNO]7 porphyrins. Thus, there is a close
      correspondence between the molecular orbitals (MOs) in the two cases. However,
      there is a critical, if somewhat subtle, difference in the nature of the singly
      occupied MOs (SOMOs) between the two. For square-pyramidal heme-NO complexes, the
      SOMO is primarily Fe d(z)2-based, which favors sigma-bonding interactions with an
      NO pi orbital, and hence a bent FeNO unit. However, for trigonal-bipyramidal
      Fe(5,5-TC)(NO), the SOMO is best described as primarily Fe d(x2-z2) in character,
      with the Fe-N(NO) vector being identified as the z direction. Apparently, such a
      d orbital is less adept at sigma bonding with NO and, as such, pi bonding
      dominates the Fe-NO interaction, leading to an essentially linear FeNO unit and a
      short Fe-N(NO) distance.

PMID- 16296824
TI  - C- and Z-shaped coordination compounds. synthesis, structure, and
      spectroelectrochemistry of cis- and trans-[Re(CO)3(L)]2-2,2'-bisbenzimidizolate
      with L = 4-phenylpyridine, 2,4'-bipyridine, or pyridine.
AB  - A series of C- and Z-shaped complexes of the form cis- and trans
      [Re(CO)3(L)]2BiBzIm, where L = 4-phenylpyridine, 2,4'-bipyridine, or pyridine and
      BiBzIm = 2,2'-bisbenzimidizolate, have been synthesized by the reaction of
      [Re(CO)4]2BiBzIm with a slight excess of L in refluxing tetrahydrofuran. Five of
      the six compounds have been isolated and crystallographically and
      electrochemically characterized. Formation of the sixth, the cis form of the
      [Re(CO)3(4-phenylpyridine)]2BiBzIm, is evidently inhibited by the torsional
      steric demands of proximal 4-phenylpyridines. The compounds are acyclic analogues
      of recently studied tetrarhenium molecular rectangles and are of interest, in
      part, because of their potential to form ligand-centered mixed-valence (LCMV)
      compounds upon reduction by one electron. Spectroelectrochemical measurements
      corroborated the formation of a LCMV version of cis-[Re(CO)3(L)]2BiBzIm but
      failed to uncover a ligand-based intervalence transition. Electrochemical
      measurements revealed isomer-dependent L/L electrostatic effects, resulting in
      greater mixed-valence ion comproportionation for C-shaped assemblies versus Z
      shaped assemblies.

PMID- 16296825
TI  - A new coordination mode of the photometric reagent glyoxalbis(2-hydroxyanil)
      (H2gbha): bis-bidentate bridging by gbha2- in the redox series [(mu
      gbha)[Ru(acac)2]2]n (n = -2, -1, 0, +1, +2), including a radical-bridged
      diruthenium(III) and a Ru(III)/Ru(IV) intermediate.
AB  - The bis-bidentate bridging function of gbha2- with N,O-/N,O- coordination was
      observed for the first time in the complex (mu-gbha)[Ru(III)(acac)2]2 (1).
      Density functional theory calculations of 1 yield a triplet ground state with a
      large (deltaE > 6000 cm(-1)) singlet-triplet gap. Intermolecular
      antiferromagnetic coupling was observed (J approximately -5.3 cm(-1)) for the
      solid. Complex 1 undergoes two one-electron reduction and two one-electron
      oxidation steps; the five redox forms [(mu-gbha)[Ru(acac)2]2]n (n = -2, -1, 0,
      +1, +2) were characterized by UV-vis-NIR spectroelectrochemistry (NIR = near
      infrared). The paramagnetic intermediates were also investigated by electron
      paramagnetic resonance (EPR) spectroscopy. The monoanion with a
      comproportionation constant K(c) of 2.7 x 10(8) does not exhibit an NIR band for
      a Ru(III)/Ru(II) mixed-valent situation; it is best described as a 1,4
      diazabutadiene radical anion containing ligand gbha*3-, which binds two
      ruthenium(III) centers. A Ru(III)-type EPR spectrum with g1 = 2.27, g2 = 2.21,
      and g3 = 1.73 is observed as a result of antiferromagnetic coupling between one
      Ru(III) and the ligand radical. The EPR-active monocation (K(c) = 1.7 x 10(6))
      exhibits a broad (deltanu(1/2) = 2600 cm(-1)) intervalence charge-transfer band
      at 1800 nm, indicating a valence-averaged (Ru3.5)2 formulation (class III) with a
      tendency toward class II (borderline situation).

PMID- 16296826
TI  - Cationic bis-cyclometalated iridium(III) diimine complexes and their use in
      efficient blue, green, and red electroluminescent devices.
AB  - A series of cationic Ir(III) complexes with the general formula
      (C/N)2Ir(N/N)(+)PF6- featuring bis-cyclometalated 1-phenylpyrazolyl-N,C2' (C/N)
      and neutral diimine (N/N, e.g., 2,2'-bipyridyl) ligands were synthesized and
      their electrochemical, photophysical, and electroluminescent properties studied.
      Density functional theory calculations indicate that the highest occupied
      molecular orbital of the compounds is comprised of a mixture of Ir d and
      phenylpyrazolyl-based orbitals, while the lowest unoccupied molecular orbital has
      predominantly diimine character. The oxidation and reduction potentials of the
      complexes can be independently varied by systematic modification of either the
      C/N or N/N ligands with donor or acceptor substituents. The electrochemical redox
      gaps (E(ox)-E(red)) were adjusted to span a range between 2.39 and 3.08 V. All of
      the compounds have intense absorption bands in the UV region assigned to 1(pi
      pi*) transitions and weaker charge-transfer (CT) transitions that extend to the
      visible region. The complexes display intense luminescence both in fluid solution
      and as neat solids at 298 K that is assigned to emission from a triplet metal
      ligand-to-ligand CT (3MLLCT) excited state. The energy of the 3MLLCT state varies
      in nearly direct proportion to the size of the electrochemical redox gap, which
      leads to emission colors that vary from red to blue. Three of the
      (C/N)2Ir(N/N)(+)PF6- complexes were used as active materials in single-layer
      light-emitting electrochemical cells (LECs). Single-layer electroluminescent
      devices were fabricated by spin-coating the Ir complexes onto an ITO-PEDOT/PSS
      substrate followed by deposition of aluminum contacts onto the organic film.
      Devices were prepared that give blue, green, and red electroluminescence spectra
      (lambda(max) = 492, 542, and 635 nm, respectively), which are nearly identical
      with the photoluminescence spectra of thin films of the same materials. The
      single-layer LECs give peak external quantum efficiencies of 4.7, 6.9, and 7.4%
      for the blue, green, and red emissive devices, respectively.

PMID- 16296827
TI  - [1,10]-Phenanthrolin-2-yl ketones and their coordination chemistry.
AB  - A synthetic protocol involving the Friedlander reaction of 8-amino-7
      quinolinecarbaldehyde followed by potassium dichromate oxidation was applied to
      2,3,4-pentanetrione-3-oxime and 1-(pyrid-2'-yl)propane-1,2-dione-1-oxime to
      provide the ligands di-(phenathrolin-2-yl)-methanone (1) and phenanthrolin-2-yl
      pyrid-2-yl-methanone (8), respectively. Ligand 1 complexed as a planar
      tetradentate with Pd(II) to form [Pd(1)](BF4)2 and with Ru(II) and two 4
      substituted pyridines (4-R-py) to form [Ru(1)(4-R-py)2](PF6)2 where R = CF3, CH3,
      and Me2N. With [Ru(bpy)2Cl2], the dinuclear complex [(bpy)2Ru(1)Ru(bpy)2](PF6)4
      was formed (bpy = 2,2'-bipyridine). Ligand 8 afforded the homoleptic Ru(II)
      complex [Ru(8)2](PF6)2, as well as the heteroleptic complex [Ru(8)(tpy)](PF6)2
      (tpy = 2,2';6,2''-terpyridine). The ligands and complexes were characterized by
      their NMR and IR spectra, as well as an X-ray structure determination of [Ru(1)(4
      CH3-py)2](PF6)2. Electrochemical analysis indicated metal-based oxidation and
      ligand-based reduction that was consistent with results from electronic
      absorption spectra. The complexes [Ru(1)(4-R-py)2](PF6)2 were sensitive to the 4
      substituent on the axial pyridine: electron donor groups facilitated the
      oxidation while electron-withdrawing groups impeded it.

PMID- 16296828
TI  - Electroactive ligands: the first metal complexes of tetrathiafulvenyl
      acetylacetonate.
AB  - The reaction of tris(alkylthio)tetrathiafulvalene thiolates with 3-chloro-2,4
      pentanedione affords tetrathiafulvalene (TTF) moieties substituted by the
      acetylacetone function (TTFSacacH), precursors of novel redox-active ligands: the
      acetylacetonate ions (TTFSacac). These TTFSacacHs have been characterized by X
      ray diffraction analyses, and similar trends have been observed, such as a TTF
      core almost planar and the acetylacetone substituent located in a plane almost
      perpendicular to the plane formed by the TTF core. Their chelating ability has
      been demonstrated by the formation of the corresponding M(TTFSacac)2(pyridine)2
      complexes in the presence of M(II)(OAc)2.H2O (M = Ni2+, Zn2+). These complexes
      with TTFSacac moieties, Ni(TTFSacac)2(pyridine)2, 6b, and
      Zn(TTFSacac)2(pyridine)2, 7b, have been characterized by X-ray diffraction
      analyses, showing in all structures the metal(II) center chelated by two TTFacac
      units in the equatorial plane and the octahedral coordination geometry around the
      metal completed by two axial pyridine ligands. Cyclic voltammetry and UV-visible
      near infrared spectroscopic measurements have evidenced a sizable interaction
      between the two electroactive ligands and the stabilization of a mixed-valence
      state in the one-electron oxidized complexes.

PMID- 16296829
TI  - Architectural isomerism in the three-dimensional polymeric spin crossover system
      [Fe(pmd)2[Ag(CN)2]2]: synthesis, structure, magnetic properties, and calorimetric
      studies.
AB  - Two coordination polymers formulated [Fe(pmd)2[Ag(CN)2]2] (pmd = pyrimidine) have
      been synthesized and characterized. Both polymers, considered to be architectural
      isomers, display different crystal structures and magnetic properties. Isomer 1
      crystallizes in the monoclinic C2/c space group with a = 6.9750(8) angstroms, b =
      16.1700(9) angstroms, c = 14.2020(8) angstroms, beta = 97.954(2) degrees, V =
      1586.37(14) angstroms3, and Z = 4. The crystal structure of isomer 2 has been
      studied at 250 and 150 K. At both temperatures, 2 displays the orthorhombic Pccn
      space group with a = 15.7700(2) [14.8950(2)] angstroms, b = 8.2980(4) [8.1580(4)]
      angstroms, c = 13.4180(6) [13.3480(5)] angstroms, V = 1755.87(14) [1621.96(10)]
      angstroms3, and Z = 4 for 250 [150] K. The iron(II) ions define distorted
      octahedral [FeN6] chromophores in both isomers. The equatorial positions are
      occupied by four [Ag(CN)2]- bridging ligands, which connect the defining layers
      of two iron(II) ions. Isomer 1 has two crystallographically distinct [Ag(CN)2]-
      groups; one is essentially linear, while the other is severely distorted [C(5)
      Ag(2)-C(5i)] = 138.8(5) degrees. This fact facilitates the parallel
      interpenetration of two layers, which in addition show short Ag(1)....Ag(2)
      interactions (distance Ag(1)....Ag(2) = 2.9972(10) angstroms). Isomer 2 shows
      only one type of Ag atom, which is slightly bent [C-Ag-C = 161.54(12) degrees],
      and as a consequence, the layers defined are not interpenetrated. In both cases,
      the axial positions are occupied by the pmd ligands which interact with the Ag
      atoms of adjacent layers defining a 3D coordination polymer. Compound 1 is high
      spin in the whole range of temperatures, while 2 undergoes a cooperative high
      spin <--> low-spin effect centered at ca. 184 K with a hysteresis loop ca. 5 K
      wide. The experimental enthalpy and entropy variations were 11.5 +/- 0.4 kJ mol(
      1) and 64 +/- 3 J K(-1) mol(-1). Consistency between the experimental
      thermodynamic data and the magnetic data was checked in the frame of regular
      solution theory.

PMID- 16296830
TI  - Synthesis and structure of Ta4S9Br8. An emergent family of early transition metal
      chalcogenide clusters.
AB  - Single crystals of Ta4S9Br8 are obtained by heating Ta, S, and Br2 at 400 degrees
      C in a 4.0:9.0:4.0 molar ratio in a 44% yield. The structure was determined by X
      ray analysis and consists of molecular clusters [Ta4(mu4-S)(mu-S2)4Br8]. The
      tantalum atoms form a square with long Ta...Ta distances (3.30 angstroms), with
      four S2 ligands bridging the Ta-Ta edges and one capping the square. Each Ta atom
      has two terminal bromine atoms. The compound is diamagnetic and has only two
      electrons for metal-metal bonding. IR and Raman spectral studies with the use of
      34S allow to identify characteristic vibrations S-S (537 cm(-1)) and Ta4-mu4-S
      (407 cm(-1)). The compound is soluble in CH3CN, giving a dark-red solution with a
      characteristic electronic spectrum, which was assigned on the base of DFT
      calculations. ESI-MS spectra of the solutions show formation of [[Ta4S9Br8]Br]-
      associates.

PMID- 16296831
TI  - Non-interpenetrated square-grid coordination polymers synthesized using an
      extremely long N,N'-type ligand.
AB  - Four new, non-interpenetrated square-grid coordination polymers, namely
      [Mn(L)2(NO3)2]infinity (1), [[Cd(L)2(NO3)2].solvate]infinity (2),
      [Cd(L)2(NO3)2]infinity (3), and [[Zn(L)2](BF4)2.(C6H6)2.564.(DMF)1.576.(MeOH,
      H2O)3.454]infinity (4), were synthesized using the new, extremely long N,N'-type
      ligand: 2,5-bis(4'-(imidazol-1-yl)benzyl)-3,4-diaza-2,4-hexadiene (L). The
      reaction of Cd(NO3)2 with L leads to two novel structures sharing the same
      framework composition, [Cd(L)2(NO3)2]infinity, which have different arrangements
      of L around the metal centers. Both the channel-containing structure and the
      nonporous structure can be formed by choice of the appropriate solvent system.
      Moreover, the less stable, channel-containing form readily converts into the more
      stable, condensed structure upon removal of the guest molecules from the
      channels.

PMID- 16296832
TI  - Syntheses; 77Se, 203Tl, and 205Tl NMR; and theoretical studies of the Tl2Se6(6-),
      Tl3Se6(5-), and Tl3Se7(5-) anions and the X-ray crystal structures of [2,2,2
      crypt-Na]4[Tl4Se8].en and [2,2,2-crypt-Na]2[Tl2Se4](infinity)1.en.
AB  - The 2,2,2-crypt salts of the Tl4Se8(4-) and [Tl2Se4(2-)]infinity1 anions have
      been obtained by extraction of the ternary alloy NaTl0.5Se in ethylenediamine
      (en) in the presence of 2,2,2-crypt and 18-crown-6 followed by vapor-phase
      diffusion of THF into the en extract. The [2,2,2-crypt-Na]4[Tl4Se8].en
      crystallizes in the monoclinic space group P2(1)/n, with Z = 2 and a = 14.768(3)
      angstroms, b = 16.635(3) angstroms, c = 21.254(4) angstroms, beta = 94.17(3)
      degrees at -123 degrees C, and the [2,2,2-crypt-Na]2[Tl2Se4]infinity1.en
      crystallizes in the monoclinic space group P2(1)/c, with Z = 4 and a = 14.246(2)
      angstroms, b = 14.360(3) angstroms, c = 26.673(8) angstroms, beta = 99.87(3)
      degrees at -123 degrees C. The TlIII anions, Tl2Se6(6-) and Tl3Se7(5-), and the
      mixed oxidation state TlI/TlIII anion, Tl3Se6(5-), have been obtained by
      extraction of NaTl0.5Se and NaTlSe in en, in the presence of 2,2,2-crypt and/or
      in liquid NH3, and have been characterized in solution by low-temperature 77Se,
      203Tl, and 205Tl NMR spectroscopy. The 1J(203,205Tl-77Se) and 2J(203,205Tl
      203,205Tl) couplings of the three anions have been used to arrive at their
      solution structures by detailed analyses and simulations of all spin multiplets
      that comprise the 205,203Tl NMR subspectra arising from natural abundance
      205,203Tl and 77Se isotopomer distributions. The structure of Tl2Se6(6-) is based
      on a Tl2Se2 ring in which each thallium is bonded to two exo-selenium atoms so
      that these thalliums are four-coordinate and possess a formal oxidation state of
      +3. The Tl4Se8(4-) anion is formally derived from the Tl2Se6(6-) anion by
      coordination of each pair of terminal Se atoms to the TlIII atom of a TlSe+
      cation. The structure of the [Tl2Se4(2-)]infinity1 anion is comprised of edge
      sharing distorted TlSe4 tetrahedra that form infinite, one-dimensional [Tl2Se42
      ]infinity1 chains. The structures of Tl3Se6(5-) and Tl3Se7(5-) are derived from
      Tl4Se4-cubes in which one thallium atom has been removed and two and three exo
      selenium atoms are bonded to thallium atoms, respectively, so that each is four
      coordinate and possesses a formal oxidation state of +3 with the remaining three
      coordinate thallium atom in the +1 oxidation state. Quantum mechanical
      calculations at the MP2 level of theory show that the Tl2Se6(6-), Tl3Se6(5-),
      Tl3Se7(5-), and Tl4Se8(4-) anions exhibit true minima and display geometries that
      are in agreement with their experimental structures. Natural bond orbital and
      electron localization function analyses were utilized in describing the bonding
      in the present and previously published Tl/Se anions, and showed that the
      Tl2Se6(6-), Tl3Se6(5-), Tl3Se7(5-), and Tl4Se8(4-) anions are electron-precise
      rings and cages.

PMID- 16296834
TI  - Cadmium(II), nickel(II), and zinc(II) complexes of vacataporphyrin: a variable
      annulene conformation inside a standard porphyrin frame.
AB  - 5,10,15,20-Tetraaryl-21-vacataporphyrin, 1 (butadieneporphyrin, annulene
      porphyrin hybrid), which contains a vacant space instead of heteroatomic bridge,
      gives diamagnetic zinc(II) 1-ZnCl and cadmium(II) 1-CdCl and paramagnetic
      nickel(II) 1-NiCl complexes. A metal ion is bound in the macrocyclic cavity by
      three pyrrolic nitrogens. Coordination imposes a steric constraint on the
      geometry of the ligand and leads to two stereoisomers with a butadiene fragment
      oriented toward 1-MCl-i or outward 1-MCl-o of the macrocyclic center. 1-CdCl-o, 1
      ZnCl-o, and the free base share a common 1H NMR spectral pattern as the basic
      structural features of 1 are preserved after metal ion insertion. The 1H NMR
      spectra of 1-CdCl-i and 1-ZnCl-i reflect a decrease of aromaticity accounted for
      by the inverted butadiene geometry. The proximity of the butadiene fragment to
      the metal ion induces direct couplings between the spin-active nucleus of the
      metal ((111/113)Cd) and the adjacent 1H nuclei of butadiene. The pattern of
      chemical shifts detected for isomeric 1-NiCl-i and 1-NiCl-o is typical for high
      spin nickel(II) complexes of porphyrin analogues. Resonances 2,3-H of 1-NiCl-o or
      1-NiCl-i present the chemical shift typical for the beta-H pyrrolic position
      despite the vacancy in the location of nitrogen-21. Coordination of imidazole,
      methanol-d4, acetonitrile-d3, or chloride converts 1-NiCl-i and 1-NiCl-o into
      distinct species which contain two axial ligands: 1-Ni(Im)2+; 1-Ni(CD3OD)2+; 1
      Ni(CD3CN)2+; 1-Ni(Cl)2-. The density functional theory (DFT) has been applied to
      model the molecular and electronic structure of feasible 1-CdCl stereoisomers.
      The total energies calculated using the B3LYP/LANL2DZ approach demonstrate a very
      small energy difference (2.3 kcal/mol) between 1-CdCl-o and 1-CdCl-i
      stereoisomers consistent with their concurrent formation.

PMID- 16296833
TI  - Sn19.3Cu4.7As22I8: a new clathrate-I compound with transition-metal atoms in the
      cationic framework.
AB  - Sn19.3Cu4.7As22I8, a new clathrate-I compound with a cationic host framework
      containing transition metals, has been synthesized, and its crystal structure has
      been determined. It crystallizes in the cubic space group Pmn with a unit cell
      parameter a = 11.1736(3) angstroms and Z = 1 (R = 0.031 for 329 independent
      reflections and 22 variables). Tin, copper, and arsenic form the cationic
      clathrate framework hosting the guest iodine anions in cages of two different
      shapes. Sn19.3Cu4.7As22I8 does not contain vacancies in the framework but reveals
      three partially occupied positions of the metal atoms, leading to the formation
      of Sn-Sn and Sn-Cu bonds that differ in length. The 119Sn Mossbauer spectrum
      confirms the local environment of tin atoms. The hyperfine constants obtained
      from the Mossbauer spectra for different cationic tin clathrates are discussed.
      Electron diffraction and electron microscopy reveal that the splitting affects
      the short-range ordering but does not lead to a superstructure. Though containing
      a transition metal, Sn19.3Cu4.7As22I8 is diamagnetic, and its composition
      corresponds to the Zintl formalism.

PMID- 16296835
TI  - Synthesis and electronic characterization of bipyridine dithiolate rhodium(III)
      complexes.
AB  - Five new mixed diimine 1,1'-dithiolate or dithiocarbamate ligand complexes of the
      form [Rh(bpy)2(SS)][PF6]n, where bpy = 2,2'-bipyridine and SS = various
      substituted dialkyldithiocarbamates or 1,1'-dithiolates, were synthesized from
      cis-[Rh(bpy)2(OTf)2][OTf]. The triflate ligands are easily displaced by other
      ligands and allow these syntheses to proceed in high yields (80-90% overall)
      under relatively mild reaction conditions and to give high purity products.
      Electrochemistry shows irreversible two-electron reduction of Rh(III) to Rh(I)
      and a concomitant loss of one bipyridine ligand; this is followed by reversible
      one-electron reduction of the remaining 2,2'-bipyridine ligand. The electronic
      characterizations of these complexes are consistent with significant
      delocalization of the sulfur electron density onto the empty metal d orbitals.
      The 1,1'-dithiolate ligands induce larger red shifts in the absorption and
      emission spectra than the dithiocarbamates as the 1,1'-dithiolates have a more
      extensive conjugation system.

PMID- 16296836
TI  - Correlation of spin states and spin delocalization with the dioxygen reactivity
      of catecholatoiron(III) complexes.
AB  - A series of catecholatoiron(III) complexes, [Fe(III)L(4Cl-cat)]BPh4 (L = (4
      MeO)2TPA (1), TPA (2), (4-Cl)2TPA (3), (4-NO2)TPA (4), (4-NO2)2TPA (5); TPA =
      tris(pyridin-2-ylmethyl)amine; 4Cl-cat = 4-chlorocatecholate), have been
      characterized by magnetic susceptibility measurements and EPR, 1H NMR, and UV-vis
      NIR spectroscopies to clarify the correlation of the spin delocalization on the
      catecholate ligand with the O2 reactivity as well as the spin-state dependence of
      the O2 reactivity. EPR spectra in frozen CH3CN at 123 K clearly showed that
      introduction of electron-withdrawing groups effectively shifts the spin
      equilibrium from a high-spin to a low-spin state. The effective magnetic moments
      determined by the Evans method in a CH3CN solution showed that 5 contains 36% of
      low-spin species at 243 K, while 1-4 are predominantly in a high-spin state.
      Evaluation of spin delocalization on the 4Cl-cat ligand by paramagnetic 1H NMR
      shifts revealed that the semiquinonatoiron(II) character is more significant in
      the low-spin species than in the high-spin species. The logarithm of the reaction
      rate constant is linearly correlated with the energy gap between the
      catecholatoiron(III) and semiquinonatoiron(II) states for the high-spin complexes
      1-3, although complexes 4 and 5 deviate negatively from linearity. The lower
      reactivity of the low-spin complex, despite its higher spin density on the
      catecholate ligand compared with the high-spin analogues, suggests the
      involvement of the iron(III) center, rather than the catecholate ligand, in the
      reaction with O2.

PMID- 16296838
TI  - Pillared-layer microporous metal-organic frameworks constructed by robust
      hydrogen bonds. Synthesis, characterization, and magnetic and adsorption
      properties of 2,2'-biimidazole and carboxylate complexes.
AB  - Two new isostructural complexes [M(H2biim)3][M(btc)(Hbiim)].2H2O (M = Co, (1); M
      = Ni, (2)) (btc = 1,3,5-benzenetricarboxylate; H2biim = 2,2'-biimidazole) have
      been synthesized and characterized by single-crystal X-ray diffraction. They
      present a unique structure consisting of two distinct units: the monomeric
      cations [M(H2biim)3]2+ and the two-dimensional (2D) anionic polymer
      [M(Hbiim)(btc)]2-. In the anionic moiety, the Hbiim- monoanion is simultaneously
      coordinated to one metal atom in a bidentate mode and further to another metal
      atom in a monodentate mode. The imidazolate groups bridge the two adjacent metal
      ions into a helical chain which is further arranged in left- and right-handed
      manners. These chains are bridged by btc ligands into a 2D brick wall structure.
      The most interesting aspect is that the [M(H2biim)3]2+ cations act as pillars and
      link the anionic layers via robust heteromeric hydrogen-bonded synthons (9) and
      (7) formed by the uncoordinated oxygen atoms of carboxylate groups and the H2biim
      ligands, resulting in a microporous metal-organic framework with one-dimensional
      (1D) channels (ca. 11.85 angstroms x 11.85 angstroms for 1 and 11.43 angstroms x
      11.43 angstroms for 2). Magnetic properties of these two complexes have also been
      studied in the temperature range of 2-300 K, and their magnetic susceptibilities
      obey the Curie-Weiss law in the temperature range of 20-300 K (for 1) and 2-300 K
      (for 2), respectively, showing anti-ferromagnetic coupling through imidazolate
      bridging. Taking into consideration the Heisenberg infinite chain model as well
      as the possibility of chain-to-chain and chain-to-cation interactions, the anti
      ferromagnetic exchange of 2 is analyzed via a correction for the molecular field,
      giving the values of g(cat) = 2.296, g(Ni) = 2.564, J = -13.30 cm(-1), and zJ' = 
      0.017 cm(-1). The microporous frameworks are stable at ca. 350 degrees C. They do
      not collapse after removal of the guest water molecules in the channels, and they
      adsorb methanol molecules selectively.

PMID- 16296837
TI  - From low-dimensional manganese(II) azido motifs to higher-dimensional materials:
      structure and magnetic properties.
AB  - Four new inorganic-organic hybrid coordination polymers in which 1D or 2D
      manganese(II) azido inorganic motifs are interlinked into higher-dimensional
      networks have been synthesized by use of a series of bis(pyridyl)-type organic
      bridging ligands (linkers) with different side groups and/or different
      coordination orientations. The dimensionality and the topology of the
      manganese(II) azido motif and the whole structure are sensitive to the organic
      linkers used. Compounds 1 and 3 are 3D coordination polymers with pillared-layer
      architectures: in 1, 2D Mn(II) layers with alternate double end-on (EO) and
      single end-to-end (EE) azido bridges are pillared by zigzag organic linkers, and
      3 is built from single EE azido-bridged Mn(II) layers and linear organic linkers.
      The 3D nets of 1, 3, and related compounds have been related to the specific
      length and coordination orientation of the organic pillars and the undulate shape
      of the manganese(II) azido layers. Consistent with their structures, both 1 and 3
      exhibit weak ferromagnetism due to spin canting. Compound 1 is a weak ferromagnet
      with T(c) = 16 K, and 3 is a metamagnet with T(c) = 23 K. On the other hand,
      compounds 2 and 4 are 2D coordination networks in which 1D manganese(II) azido
      chains are interlinked by organic linkers: 2 is the first 2D network built from
      Mn(II) chains with alternate double EE and double EO azido bridges, which mediate
      antiferro- and ferromagnetic interactions, respectively; 4 is the first 2D
      network built from Mn(II) chains with only single EE azido bridges, which mediate
      antiferromagnetic interactions. The magnetic susceptibility of 4 exhibits a rapid
      rise at very low temperature, which may be attributed to paramagnetic impurities
      or spin canting.

PMID- 16296839
TI  - Polyoxometalate-supported transition metal complexes and their charge
      complementarity: synthesis and characterization of
      [M(OH)6Mo6O18[Cu(Phen)(H2O)2]2][M(OH)6Mo6O18[Cu(Phen)(H2O)Cl]2].5H2O (M = Al(+,
      Cr3+).
AB  - Two Anderson-type heteropolyanion-supported copper phenanthroline complexes,
      [Al(OH)6Mo6O18[Cu(phen)(H2O)2]2]1+ (1c) and [Al(OH)6Mo6O18[Cu(phen)(H2O)Cl]2]1-
      (1a) complement their charges in one of the title compounds
      [Al(OH)6Mo6O18[Cu(phen)(H2O)2]2][Al(OH)6Mo6O18[Cu(phen)(H2O)Cl]2].5H2O [1c][1a].5
      H2O 1. Similar charge complementarity exists in the chromium analogue,
      [Cr(OH)6Mo6O18[Cu(phen)(H2O)2]2][Cr(OH)6Mo6O18[Cu(phen)(H2O)Cl]2].5 H2O
      [2c][2a].5 H2O 2. The chloride coordination to copper centers of 1a and 2a makes
      the charge difference. In both compounds, the geometries around copper centers
      are distorted square pyramidal and those around aluminum/chromium centers are
      distorted octahedral. Three lattice waters, from the formation of intermolecular
      O-H.....O hydrogen bonds, have been shown to self-assemble into an "acyclic water
      trimer" in the crystals of both 1 and 2. The title compounds have been
      synthesized in a simple one pot aqueous wet-synthesis consisting of
      aluminum/chromium chloride, sodium molybdate, copper nitrate, phenanthroline, and
      hydrochloric acid, and characterized by elemental analyses, EDAX, IR, diffuse
      reflectance, EPR, TGA, and single-crystal X-ray diffraction. Both compounds
      crystallize in the triclinic space group P. Crystal data for 1: a = 10.7618(6), b
      = 15.0238(8), c = 15.6648(8) angstroms, alpha = 65.4570(10), beta = 83.4420(10),
      gamma = 71.3230(10), V = 2182.1(2) angstroms3. Crystal data for 2: a =
      10.8867(5), b = 15.2504(7), c = 15.7022(7) angstroms, alpha = 64.9850(10), beta =
      83.0430(10), gamma = 71.1570(10), V = 2235.47(18) angstroms3. In the electronic
      reflectance spectra, compounds 1 and 2 exhibit a broad d-d band at approximately
      700 nm, which is a considerable shift with respect to the value of 650-660 nm for
      a square-pyramidal [Cu(phen)2L] complex, indicating the coordination of
      [M(OH)6Mo6O18]3- POM anions (as a ligand) to the monophenanthroline copper
      complexes to form POM-supported copper complexes 1c, 1a, 2c, and 2a. The ESR
      spectrum of compound 1 shows a typical axial signal for a Cu2+ (d9) system, and
      that of compound 2, containing both chromium(III) and copper(II) ions, may reveal
      a zero-field-splitting of the central Cr3+ ion of the Anderson anion,
      [Cr(OH)6Mo6O18]3-, with an intense peak for the Cu2+ ion.

PMID- 16296840
TI  - Semiconductive coordination networks from bismuth(III) bromide and 1,2
      bis(methylthio)phenylacetylene-based ligands.
AB  - This paper reports our initial efforts to integrate phenylacetylene-based
      conjugate pi-electron systems into hybrid semiconductive coordination networks,
      as part of the larger scheme to fully synergize organic functionalities and
      electronic properties in crystalline solid-state materials. On the basis of a
      well-established Pd-catalyzed procedure, ligands of 3,3',4,4'
      tetrakis(methylthio)tolan (L1) and 1,3,5-tris[[3,4
      bis(methylthio)phenyl]ethynyl]benzene (L2) were efficiently synthesized in
      relatively simple procedures. Molecule L1 reacts with BiBr3 to form a 2D
      semiconductive coordination network (L1.2BiBr3), which consists of infinite
      chains of the BiBr3 component cross-linked by L1 through the chelation between
      the 1,2-bis(methylthio) groups and the Bi(III) centers. Molecule L2 reacts with
      BiBr3 to from a 1D semiconductive coordination network (L2.2BiBr3), which
      features discrete tetrameric Bi4Br12 units linked by the thioether groups from L2
      [only two of the three 1,2-bis(methylthio) groups from each L2 molecule are
      bonded to the Bi(III) centers]. Diffuse reflectance spectra of both L1.2BiBr3 and
      L2.2BiBr3 feature strong optical absorptions at energy levels significantly lower
      than those of the corresponding molecular solids (L1 and L2) and BiBr3,
      indicating significant electronic interaction between the organic pi-electron
      systems and the BiBr3 components. Both L1.2BiBr3 and L2.2BiBr3 readily form in
      high yields and are stable to air, providing advantages for further studies as
      potentially applicable semiconductive materials.

PMID- 16296841
TI  - Solvothermal syntheses of [Ln(en)3(H2O)x(mu(3-x)-SbS4)] (Ln = La, x = 0; Ln = Nd,
      x = 1) and [Ln(en)4]SbS4.0.5en (Ln = Eu, Dy, Yb): a systematic study on the
      formation and crystal structures of new lanthanide thioantimonates(V).
AB  - New lanthanide thioantimonate(V) compounds, [Ln(en)3(H2O)x(mu(3-x)-SbS4)] (en =
      ethylenediamine, Ln = La, x = 0, Ia; Ln = Nd, x = 1, Ib) and [Ln(en)4]SbS4.0.5en
      (Ln = Eu, IIa; Dy, IIb; Yb, IIc), were synthesized under mild solvothermal
      conditions by reacting Ln2O3, Sb, and S in en at 140 degrees C. These compounds
      were classified as two types according to the molecular structures. The crystal
      structure of type I (Ia and Ib) consists of one-dimensional neutral
      [Ln(en)3(H2O)x(mu(3-x)-SbS(4))]infinity (x = 0 or 1) chains, in which SbS4(3-)
      anions act as tridentate or bidentate bridging ligands to interlink [Ln(en)3]3+
      ions, while the crystal structure of type II (IIa, IIb, and IIc) contains
      isolated [Ln(en)4]3+ cations, tetrahedral SbS4(3-) anions, and free en molecules.
      A systematic investigation of the crystal structures of the five lanthanide
      compounds, as well as two reported compounds, clarifies the relationship between
      the molecular structure and the entity of the lanthanide(III) series, such as the
      stability of the lanthanide(III)-en complexes, the coordination number, and the
      ionic radii of the metals.

PMID- 16296842
TI  - Structural constraints in the design of silver sulfonate coordination networks:
      three new polysulfonate open frameworks.
AB  - Three new silver sulfonate metal-organic frameworks are presented along with a
      design strategy for future generations.
      [[Ag6(mesitylenetrisulfonate)2(H2O)5].2H2O]infinity (1),
      [Ag4(durenetetrasulfonate)(H2O)2](infinity) (2), and [[Ag4(1,3,5,7-tetrakis(4,4'
      sulfophenyl)adamantane)(H2O)2].1.3H2O]infinity (3) represent a series of open
      framework silver sulfonate solids where the organic linker plays a key role in
      determining the overall structure. Compound 1 forms a pillared layered structure,
      while compounds 2 and 3 form 3-D nets derived from cross-linking of 1-D columns
      of silver sulfonates. All three solids incorporate water molecules, which can be
      removed to yield a solid stable to in excess of 300 degrees C. Powder X-ray
      diffraction studies and vapor sorption experiments show, for 1 and 2, that the
      solids retain their structure when guests are removed and, for all three, that
      water vapor is resorbed stoichiometrically by the solids. An idealized silver
      sulfonate framework is proposed, and upon comparison to the reported structures,
      guidelines are proposed for structural constraints in the design of future
      generations of 1-D and possibly 0-D aggregate structures.

PMID- 16296843
TI  - Steric protection of a photosensitizer in a N,N-bis[2-(2-pyridyl)ethyl]-2
      phenylethylamine-copper(II) bowl that enhances red light-induced DNA cleavage
      activity.
AB  - Ternary copper(II) complexes [Cu(py2phe)B](ClO4)2 (1-3), where py2phe is a
      tripodal ligand N,N-bis[2-(2-pyridyl)ethyl]-2-phenylethylamine and B is a
      heterocyclic base (viz., 1,10-phenanthroline (phen, 1), dipyrido[3,2-d:2',3'
      f]quinoxaline (dpq, 2), or dipyrido[3,2-a:2',3'-c]phenazine (dppz, 3)), are
      prepared and their DNA-binding and photoinduced DNA-cleavage activities are
      studied. Complex 1 has been structurally characterized by single crystal X-ray
      crystallography. The molecular structure shows an axially elongated square
      pyramidal (4 + 1) coordination geometry in which the phen ligand binds at the
      basal plane. The tripodal ligand py2phe displays an axial-equatorial binding mode
      with the amine nitrogen bonded at the axial site. A chemically significant CH-pi
      interaction involving the CH moiety of the phenyl group of the tripodal ligand
      and the aromatic ring of phen is observed. The complexes display good binding
      propensity to calf thymus DNA giving a relative order of 3 (dppz) > 2 (dpq) > 1
      (phen). The DNA binding constants (K(b)) for 1-3, determined from absorption
      spectral studies, are 6.2 x 10(3), 1.0 x 10(4), and 5.7 x 10(4) M(-1),
      respectively. The complexes show chemical nuclease activity in the presence of 3
      mercaptopropionic acid as a reducing agent forming hydroxyl radicals as the
      cleavage active species. The photoinduced DNA-cleavage activity of the complexes
      has been studied using UV radiation of 365 nm and red light of 632.8 and 694 nm.
      The phen complex in absence of any photosensitizing moiety does not show any DNA
      cleavage upon photoirradiation. The dpq and dppz ligands with their photoactive
      quinoxaline and phenazine moieties display significant photoinduced DNA-cleavage
      activity. The dppz complex is more active than its dpq analogue because of the
      better steric protection of the DNA-bound photosensitizing dppz ligand from the
      solvent molecules. Control experiments reveal the formation of singlet oxygen in
      the light-induced DNA-cleavage reactions. The observed efficient photoinduced DNA
      cleavage activity of 2 and 3 is akin to the "light switch" effect known for the
      tris-chelates of ruthenium(II).

PMID- 16296844
TI  - Barriers to racemization in C3-symmetric complexes containing the hydrotris(2
      mercapto-1-ethylimidazolyl)borate (Tm(Et)) ligand.
AB  - The tripodal ligands hydrotris(N-ethyl-2-mercaptoimidazol-1-yl)borate (NaTm(Et))
      (1) and hydrotris(N-benzyl-2-mercaptoimidazol-1-yl)borate (NaTm(Bn)) (2),
      analogues of the hydrotris(N-methyl-2-mercaptoimidazol-1-yl)borate ligand (Tm)
      containing alternative nitrogen substituents, have been employed to examine the
      racemization of their C3-symmetric complexes with both four- and six-coordinate
      metals. The ligands react at room temperature with metal halides to provide C3
      symmetric metal complexes. The syntheses of the four-coordinate complexes
      [Tm(Et)ZnCl] (3), [Tm(Et)CdBr] (4), [Tm(Et)HgCl] (5), [Tm(Et)CuPPh3] (6),
      [Tm(Et)AgPPh3] (7), and [Tm(Bn)ZnCl] (8) are reported. The six-coordinate
      complexes [Tm(Et)Ru(p-cymene)]Cl (9), [Tm(Et)Ru(p-cymene)]PF(6) (10), and
      [Tm(Et)Mn(CO)3] (11) were also synthesized. The X-ray crystal structures of 3, 4,
      6, and 9 are reported. The diastereotopic nature of the ethyl and benzyl hydrogen
      atoms in the ligands allows the enantiomeric forms of these complexes to be
      distinguished by 1H NMR spectroscopy. Variable-temperature (VT) 1H NMR spectra
      have thus been used to investigate the energies of the racemization processes
      occurring in these chiral complexes. In solvents the activation energies to
      racemization for the four-coordinate complexes lay in the range of 53-77 kJ mol(
      1). In non-donor solvents the energies are reduced and a dissociative mechanism
      is therefore implicated. No interconversion could be observed by VT NMR for the
      six-coordinate complexes in any solvent. To further explore the racemization
      mechanisms ab initio density functional theory calculations have been conducted
      on the ground- and transition-state structures of representative six-coordinate
      [Mn(I)] and four-coordinate [Zn(II)] complexes following a proposed
      nondissociative mechanism of racemization. The calculated energy barriers to
      racemization are 163 and 121 kJ mol(-1), respectively. It is concluded that the
      low-energy racemization of substitution-labile four-coordinate complexes occurs
      via a dissociative mechanism, while substitution-inert six-coordinate complexes
      experience a significantly higher barrier to racemization. Whether this is due to
      the operation of a dissociative mechanism with a higher activation barrier or to
      a nondissociative mechanism remains unknown.

PMID- 16296845
TI  - Thioether complexes of palladium(II) and platinum(II) as artificial peptidases.
      residue-selective peptide cleavage by a palladium(II) complex.
AB  - We report the synthesis and characterization of perchlorate salts containing the
      following three novel complex cations each with a bidentate thioether ligand:
      binuclear cis-[Pt(CH3SCH2CH2CH2SCH3)(mu-OH)]22+, mononuclear cis
      [Pt(CH3SCH2CH2CH2SCH3)(H2O)2]2+, and mononuclear cis
      [Pd(CH3SCH2CH2CH2SCH3)(H2O)2]2+. Despite their analogous compositions, the
      mononuclear Pt(II) and Pd(II) complexes differ in the selectivity with which they
      promote the hydrolysis of polypeptides. The complex cis
      [Pt(CH3SCH2CH2CH2SCH3)(H2O)2]2+ promotes slow but selective cleavage of Met-Pro
      peptide bonds at pH 2.0. The selectivity of the complex cis
      [Pd(CH3SCH2CH2CH2SCH3)(H2O)2]2+ is pH-dependent. At pH 2.0, this Pd(II) complex
      promotes residue-selective hydrolysis of the X-Y bond in X-Y-Met and X-Y-His
      sequences; the rate is enhanced when residue Y is proline. At pH 7.0, this
      kinetic preference becomes sequence-selective in that the Pd(II) complex
      exclusively cleaves the X-Pro bond in X-Pro-Met and X-Pro-His sequences. The
      enhanced reactivity of the X-Pro amide group is attributed to the high basicity
      of its carbonyl oxygen atom. Binding of the metal(II) atom enhances the
      electrophilicity of the carbonyl carbon atom and promotes nucleophilic attack by
      a solvent water molecule. The bidentate thioether ligand disfavors the formation
      of hydrolytically unreactive complexes, allowing the Pd(II) complex to promote
      the cleavage reaction.

PMID- 16296846
TI  - Isomers of cyclo-heptasulfur and their coordination to Li(+): an ab initio
      molecular orbital study.
AB  - The potential energy hypersurfaces (PESs) of heptasulfur (S7) and of [LiS7]+ have
      been investigated by ab initio molecular orbital calculations at the G3X(MP2)
      level of theory. Besides the chair-like seven-membered ring (1a) as the global
      minimum structure, eight local minimum structures and one transition state have
      been located on the PES of S7. The barrier for pseudorotation of 1a is only 5.6
      kJ mol(-1). The boat-like S7 ring (1b) is 12.1 kJ mol(-1) less stable than 1a,
      followed by three isomers of connectivity S6=S and four open-chain isomers. On
      the basis of multireference calculations at the MRCI(4,4)+Q/6-311G(d) level, the
      most stable open-chain form of S7 is a triplet of relative energy 133.1 kJ mol(
      1). Thus, the reaction energy (deltaE0) for the ring opening of 1a is 133.1 kJ
      mol(-1), halfway between those of the highly symmetrical rings S6 and S8. Because
      of their strong multireference characters, the stabilities of the biradicalic
      singlet chains are significantly overestimated by the single-reference-based
      G3X(MP2) method. The calculated vibrational spectrum of 1a is in good agreement
      with experimental data. The various isomers of S7 form stable complexes with Li+
      with coordination numbers of 1-4 for the metal atom and binding energies in the
      range of -93.8 to -165.7 kJ mol(-1). A total of 15 isomeric complexes have been
      located, with 13 of them containing cyclic ligands. The global minimum structure
      (2a) is composed of 1a, with the Li+ cation linked to the four negatively charged
      sulfur atoms (symmetry C(s)). The corresponding complex 2c containing the ligand
      1b is by 23.4 kJ mol(-1) less stable than 2a, and a bicyclic crown-shaped LiS7
      cation (2e) is by 34.9 kJ mol(-1) less stable than 2a. Even less stable are four
      complexes with the branched S6=S ligand. SS bond activation by polarization of
      the valence electrons takes place on coordination of Li+ to cyclo-S7 (1a).

PMID- 16296847
TI  - Complexation to Fe(II), Ni(II), and Zn(II) of multidentate ligands resulting from
      condensation of 2-pyridinecarboxaldehyde with alpha,omega-triamines: selective
      imidazolidine/hexahydropyrimidine ring opening revisited.
AB  - The condensation reaction between 2-pyridinecarboxaldehyde and
      diethylenetriamine, 3-[(2-aminoethyl)amino]propylamine, and 3,3'
      iminobis(propylamine) in a 2:1 molar ratio yields ligands that may be isolated
      exclusively in the dissymmetric (cyclic) isomeric forms L(A), L(B)/L(B*), and
      L(C). The template effect of a metal center (Fe(II), Ni(II), and Zn(II)) results
      in the ring opening of L(C) including one hexahydropyrimidine ring and one (long)
      propylene bridge. The resulting symmetric bis-Schiff base isomeric form L(C') is
      stabilized through pentacoordination, yielding [Fe(II)L(C')(NCS)](NCS) (3),
      [Ni(II)L(C')(NCS)](NCS) (6), and [Zn(II)L(C')(NCS)](NCS) (9). The same metal
      centers are too bulky to exert a template effect on L(A) including one
      imidazolidine ring and one (short) ethylene bridge. L(A) acts as a tetradentate
      ligand yielding [Fe(II)L(A)(NCS)2] (1), [Ni(II)L(A)(NCS)2] (4), and
      [Zn(II)L(A)(NCS)2] (7). The template effect of the metal center is selective
      toward the ligand L(B)/L(B*) including a hexahydropyrimidine (imidazolidine) ring
      and the shorter ethylene (longer propylene) bridge. The Fe(II) cation is small
      enough to exert a template effect, resulting in the ring opening of L(B)/L(B*).
      The resulting bis-Schiff base L(B') is stabilized through pentacoordination,
      yielding [Fe(II)L(B')(NCS)](NCS) (2). Ni(II) is too bulky to promote the ring
      opening of L(B)/L(B*): L(B) acts as a tetradentate ligand, yielding
      [Ni(II)L(B)(NCS)2] (5) (the L(B*) isomer is totally converted to L(B)). The
      coordinative requirements and stereochemical preference of the bulkier Zn(II)
      cation allow neither the ring opening of L(B)/L(B*) nor the tetracoordination of
      L(B) or L(B*) but stabilize the novel tetradentate dissymmetric form L(B degrees)
      in [Zn(II)L(B degrees)(NCS)2].H2O (8) (L(B degrees) results from MeOH addition
      across the imine bond of L(B)). Density functional theory calculations performed
      for Ni(II) and Zn(II) complexes of the L(B)/L(B*)/L(B degrees) set of ligands
      allowed one to compare the relative stabilities of all possible isomers, showing
      that the most stable ones correspond to those experimentally obtained:
      isomerization, or methanol addition across the imine bond, of the tetradentate
      ligand depends on the relative stabilities of all possible isomeric complexes.

PMID- 16296848
TI  - Tuning the triplet energy levels of pyrazolone ligands to match the 5D0 level of
      europium(III).
AB  - Three pyrazolone-based ligands, namely 1-phenyl-3-methyl-4-(1-naphthoyl)-5
      pyrazolone (HL1), 1-phenyl-3-methyl-4-(4-dimethylaminobenzoyl)-5-pyrazolone
      (HL2), and 1-phenyl-3-methyl-4-(4-cyanobenzoyl)-5-pyrazolone (HL3), were
      synthesized by introducing electron-poor or electron-rich aryl substituents at
      the 4-position of the pyrazolone ring. Their corresponding europium complexes
      Eu(LX)3(H2O)2 and Eu(LX)3(TPPO)(H2O) (X = 1-3) were characterized by
      photophysical studies. The characteristic Eu(III) emission of these complexes
      with at most 9.2 x 10(-3) of fluorescent quantum yield was observed at room
      temperature. The results show that the modification of ligands tunes the triplet
      energy levels of three pyrazolone-based ligands to match the 5D0 energy level of
      Eu3+ properly and improves the energy transfer efficiency from antenna to Eu3+,
      therefore enhancing the Eu(III) emission intensity. The highest energy transfer
      efficiency and probability of lanthanide emission of Eu(L1)3(H2O)2 are 35.1% and
      2.6%, respectively, which opens up broad prospects for improving luminescent
      properties of Eu(III) complexes by the modification of ligands. Furthermore, the
      electroluminescent properties of Eu(L1)3(TPPO)(H2O) were also investigated.

PMID- 16296850
TI  - Tautomerization of methyldiazene to formaldehyde-hydrazone in ruthenium and
      osmium complexes.
AB  - Mixed-ligand hydrazine complexes [M(CO)(RNHNH2)P4](BPh4)2 (1, 2) [M = Ru, Os; R =
      H, CH3, C6H5; P = P(OEt)3] with carbonyl and triethyl phosphite were prepared by
      allowing hydride [MH(CO)P4]BPh4 species to react first with HBF4.Et2O and then
      with hydrazines. Depending on the nature of the hydrazine ligand, the oxidation
      of [M(CO)(RNHNH2)P4](BPh4)2 derivatives with Pb(OAc)4 at -30 C gives acetate
      [M(kappa1-OCOCH3)(CO)P4]BPh4 (3a), phenyldiazene [M(CO)(C6H5N=NH)P4](BPh4)2 (3c,
      4c), and methyldiazene [M(CO)(CH3N=NH)P4](BPh4)2 (3b, 4b) derivatives.
      Methyldiazene complexes 3b and 4b undergo base-catalyzed tautomerization of the
      CH3N=NH ligand to formaldehyde-hydrazone NH2N=CH2, giving the
      [M(CO)(NH2N=CH2)P4](BPh4)2 (5, 6) derivatives. Complexes 5 and 6 were
      characterized spectroscopically and by the X-ray crystal structure determination
      of the [Ru(CO)(NH2N=CH2)[P(OEt)3]4](BPh4)2 (5) derivative. Acetone-hydrazone
      [M(CO)[NH2N=C(CH3)2]P4](BPh4)2 (7, 8) complexes were also prepared by allowing
      hydrazine [M(CO)(NH2NH2)P4](BPh4)2 derivatives to react with acetone.

PMID- 16296851
TI  - Electron exchange between alpha-Keggin tungstoaluminates and a well-defined
      cluster-anion probe for studies in electron transfer.
AB  - Fully oxidized alpha-AlIIIW12O40(5-) (1ox), and one-electron-reduced alpha
      AlIIIW12O40(6-) (1red), are well-behaved (stable and free of ion pairing) over a
      wide range of pH and ionic-strength values at room temperature in water. Having
      established this, 27Al NMR spectroscopy is used to measure rates of electron
      exchange between 1ox (27Al NMR: 72.2 ppm relative to Al(H2O)63+; nu(1/2) = 0.77
      Hz) and 1red (74.1 ppm; nu(1/2) = 0.76 Hz). Bimolecular rate constants, k, are
      obtained from line broadening in 27Al NMR signals as ionic strength, mu, is
      increased by addition of NaCl at the slow-exchange limit of the NMR time scale.
      The dependence of k on is plotted using the extended Debye-Huckel equation: log k
      = log k0 + 2alphaz1z2mu(1/2)/(1 + betarnu(1/2)), where z1 and z2 are the charges
      of 1ox and 1red, alpha and beta are constants, and r, the distance of closest
      contact, is fixed at 1.12 nm, the crystallographic diameter of a Keggin anion.
      Although not derived for highly charged ions, this equation gives a straight line
      (R2 = 0.996), whose slope gives a charge product, z1z2, of 29 +/- 2,
      statistically identical to the theoretical value of 30. Extrapolation to mu = 0
      gives a rate constant k11 of (6.5 +/- 1.5) x 10(-3) M(-1) s(-1), more than 7
      orders of magnitude smaller than the rate constant [(1.1 +/- 0.2) x 10(5) M(-1)
      s(-1)] determined by 31P NMR for self-exchange between P(V)W12O40(3-) and its one
      electron-reduced form, P(V)W12O40(4-). Sutin's semiclassical model reveals that
      this dramatic difference arises from the large negative charges of 1ox and 1red.
      These results, including independent verification of k11, recommend 1red as a
      well-behaved electron donor for investigating outer-sphere electron transfer to
      molecules or nanostructures in water, while addressing a larger issue, the
      prediction of collision rates between uniformly charged nanospheres, for which
      1ox and 1red provide a working model.

PMID- 16296849
TI  - A family of oxo-chalcogenide molybdenum and tungsten complexes, (n-Bu4N)2[M2O2(mu
      Q)2(1,3-dithiole-2-thione-4,5-dithiolate)2] (M = Mo, W; Q = S, Se): new synthetic
      entries, structure, and gas-phase behavior.
AB  - A new series of complexes with the general formula (n-Bu4N)2[M2O2(micro
      Q)2(dmit)2] (where M = Mo, W; Q = S, Se; dmit = 1,3-dithiole-2-thione-4,5
      dithiolate) have been prepared. Fragmentation of the trinuclear cluster (n
      Bu4N)2[Mo3(micro3-S)(micro-S2)3(dmit)3] in the presence of triphenylphosphine
      (PPh3) gives the dinuclear compound (n-Bu4N)2[Mo2O2(micro-S)2(dmit)2] [(n
      Bu4N)2[2]], which is formed via oxidation in air from the intermediate (n
      Bu4N)2[Mo3(micro3-S)(micro-S)3(dmit)3] [(n-Bu4N)2[1]] complex. Ligand
      substitution of the molybdenum sulfur bridged [Mo2O2(micro
      S)2(dimethylformamide)6]2+ dimer with the sodium salt of the dmit dithiolate also
      affords the dianionic compound (n-Bu4N)2[2]. The whole series, (n
      Bu4N)2[Mo2O2(micro-Se)2(dmit)2] [(n-Bu4N)2[3]], (n-Bu4N)2[W2O2(micro-S)2(dmit)2]
      [(n-Bu4N)2[4]], (n-Bu4N)2[W2O2(micro-Se)2(dmit)2] [(n-Bu4N)2[5]], and (n
      Bu4N)2[Mo2O2(micro-S)2(dmid)2] [(n-Bu4N)2[6]; dmid = 1,3-dithiole-2-one-4,5
      dithiolate], has been synthesized by the excision of the polymeric (Mo3Q7Br4)x
      phases with PPh3 or 1,2-bis(diphenylphosphanyl)ethane in acetonitrile followed by
      the dithiolene incorporation and further degradation in air. Direct evidence of
      the presence of the intermediates with the formula [M3Q4(dmit)3]2- (M = Mo, W; Q
      = S, Se) has been obtained by electrospray ionization mass spectrometry. The
      crystal structures of (n-Bu4N)2[1], (PPh4)2[Mo2O2(micro-S)2(dmit)2] [(PPh4)2[2];
      PPh4 = tetraphenylphosphonium], (n-Bu4N)2[2], (n-Bu4N)2[4], (PPh4)2[W2O2(micro
      Se)2(dmit)2] [(PPh4)2[5]], and (n-Bu4N)2[6] have been determined. A detailed
      study of the gas-phase behavior for compounds (n-Bu4N)2[2-6] shows an identical
      fragmentation pathway for the whole family that consists of a partial breaking of
      the two dithiolene ligands followed by the dissociation of the dinuclear cluster.

PMID- 16296852
TI  - Terpyridine Zn(II), Ru(III), and Ir(III) complexes: the relevant role of the
      nature of the metal ion and of the ancillary ligands on the second-order
      nonlinear response of terpyridines carrying electron donor or electron acceptor
      groups.
AB  - Coordination of 4'-(C6H4-p-X)-2,2':6',2''-terpyridines [X = NO2, NBu2, (E)-CH=CH
      C6H4-p-NBu2, (E,E)-(CH=CH)2-C6H4-p-NMe2] to Zn(II), Ru(III), and Ir(III) metal
      centers induces a significant enhancement of the absolute value of the second
      order nonlinear optical (NLO) response of the terpyridine, measured by means of
      both electric field induced second harmonic generation and solvatochromic
      methods. By varying the nature of the metal center, the enhanced second-order NLO
      response shifts from positive to negative. Such a shift is controlled by
      electronic charge-transfer transitions, such as metal-to-ligand or ligand-to
      metal transitions, in addition to the intraligand charge transfer. The
      enhancement generated by coordination is also controlled by the chelation effect
      and by fine-tuning of the ancillary ligands.

PMID- 16296853
TI  - Gadolinium and neodymium citrates: evidence for weak ferromagnetic exchange
      between gadolinium(III) cations.
AB  - A new lanthanide citrate motif of general formula [Ln(Hcit)(H2O)2.H2O]n, where Ln
      = Gd (1) and Nd (2) and Hcit3- = C(OH)(COO-)(CH2COO-)2, has been synthesized
      hydrothermally from Ln2O3 and citric acid at 100 degrees C and characterized by
      elemental analysis, IR, TG-DTA, single-crystal X-ray diffraction, and magnetic
      measurements. The structures can be seen as "ladder chains" along the a axis,
      with dinuclear Ln2O2 units serving as "steps" and R-COO groups as "uprights",
      which are connected by H bonds. The magnetic susceptibility between 2 and 300 K
      and the magnetization at 2 K, as a function of magnetic field between 0 and 5 T,
      were measured for both compounds. By modeling the magnetic behavior of the Gd
      compound with a dinuclear Hamiltonian [symbol: see text](S) = gmu(B)(S(A) +
      S(B))B(o) - J(o)S(A)S(B) (S(A) = S(B) = 7/2), a ferromagnetic exchange
      interaction J(o) = 0.039 cm(-1) was evaluated between Gd ions situated at d(o) =
      4.321 angstroms in dinuclear units bridged by two symmetry-related tridentate
      carboxylate oxygens. The EPR spectrum of the Gd compound is discussed. The
      temperature dependence of the susceptibility of the Nd compound is caused by the
      depopulation of the excited crystal-field levels when the temperature decreases.
      The magnetic-field dependence of the magnetization of 2 is attributed to the
      ground-state Kramers' doublet populated at 2 K. The g factor of this ground-state
      doublet is calculated from the data and compared with values for other compounds
      reported in the literature.

PMID- 16296854
TI  - Examination of the bonding in binary transition-metal monophosphides MP (M = Cr,
      Mn, Fe, Co) by X-ray photoelectron spectroscopy.
AB  - The binary transition-metal monophosphides CrP, MnP, FeP, and CoP have been
      studied with X-ray photoelectron spectroscopy. The shifts in phosphorus 2p(3/2)
      core line binding energies relative to that of elemental phosphorus indicated
      that the degree of ionicity of the metal-phosphorus bond decreases on progressing
      from CrP to CoP. The metal 2p(3/2) core line binding energies differ only
      slightly and show similar line shapes to those of the elemental metals,
      reaffirming the notion that these transition-metal phosphides have considerable
      metallic character. The satellite structure observed in the Co 2p(3/2) X-ray
      photoelectron spectra of Co metal and CoP was examined by reflection electron
      energy loss spectroscopy and has been attributed to plasmon loss, not final state
      effects as has been previously suggested. Valence-band spectra of the transition
      metal phosphides agree well with the density of states profiles determined from
      band structure calculations. The electron populations of the different electronic
      states were extracted from the fitted valence-band spectra, and these confirm the
      presence of strong M-P and weak P-P bonding interactions. Atomic charges
      determined from the P 2p core line spectra and the fitted valence-band spectra
      support the approximate formulation M(1+)P(1-) for these phosphides.

PMID- 16296855
TI  - Redox properties of wild-type and heme-binding loop mutants of bacterial
      cytochromes C measured by direct electrochemistry.
AB  - We have used protein film voltammetry (PFV) to determine the midpoint potentials
      of the Pseudomonas aeruginosa, Hydrogenobacter thermophilus, and Nitrosomonas
      europaea wild-type monoheme cytochromes c (cyts c; PA, HT, and NE, respectively),
      as well as PA N64Q, HT Q64N, and NE V65delta mutants, as a function of pH, and
      buffer conditions. Recent studies have suggested that the identity of the 64
      position of the heme-binding loop (either Asn or Gln) strongly influences the
      conformation of the Met ligand that binds the heme iron. The PFV studies reveal
      that HT and NE possess significantly lower potentials (wild-type cyts c having
      E(m) values of +227 and +250 mV vs SHE) than PA (+290 mV) in 50 mM phosphate
      buffer, pH 7 at 3 degrees C. The HT Q64N mutant rises in potential compared to
      wild-type, and the PA N64Q mutant has a lower potential, indicating relationships
      between Met ligand fluxion, hydrogen bonding to the Met ligand, and redox
      chemistry. Surprisingly, NE V65delta, possessing a heme binding loop nearly
      identical to that of the PA protein, displayed an E(m) of +232 mV, even lower
      than wild-type NE. These data are discussed in terms of models of Met ligand
      properties and proton dependence.

PMID- 16296856
TI  - Synthesis and molecular structures of mononitrosyl (N2S2)M(NO) complexes (M = Fe,
      Co).
AB  - A series of tetragonally distorted square pyramids of formula N2S2M(NO) (M = Fe,
      Co) is prepared and characterized by nu(NO) IR and EPR spectroscopies, magnetism
      and electrochemical properties, as well as solid-state crystal structure
      determinations. While the nu(NO) IR frequencies and the angleM-N-O angles
      indicate differences in the electronic environment of NO consistent with the
      Enemark-Feltham notation of [Fe(NO)]7 and [Co(NO)]8, the reduction potentials,
      assigned to [Fe(NO)]7 + e- <==> [Fe(NO)]8 and [Co(NO)]8 + e- <==> [Co(NO)]9
      respectively, are very similar, and in cases identical, for most members of the
      series. Coupled with the potential for the M(NO) units to breathe out of and into
      the N2S2 core plane are unique S-M-N-O torsional arrangements and concomitant pi
      bonding interactions which may account for the unusual coherence of reduction
      potentials within the series.

PMID- 16296857
TI  - Ion pairing in Ti(IV) trisamidotriazacyclononane compounds.
AB  - [Ti[N(Ph)SiMe2]3-tacn]X complexes (X = Cl, 1; I, 2; PF6, 3; BPh4, 4) were studied
      by NMR and electron absorption and emission methods, which showed that these
      compounds exist in bromobenzene and dichloromethane solutions as ion pairs. The
      significant modifications observed in the proton resonances of tacn in C6D5Br,
      which follow the sequence BPh(4-) > or = PF(6-) > or = I- approximately Cl-, are
      a qualitative indication of the strength of the interactions that depend on the
      anion. The reaction of 2 with LiNMe2 led to [Ti(NPh)[NPh(SiMe2)]2-tacn], 5, that
      forms upon attack of Me2N- at one SiMe2 group. The formation of 5 is discussed on
      the basis of the interactions identified in solution.

PMID- 16296858
TI  - Electrochemistry and spectroelectrochemistry of heterobimetallic porphyrin
      corrole dyads. Influence of the spacer, metal ion, and oxidation state on the
      pyridine binding ability.
AB  - Combined electrochemical and UV-visible spectroelectrochemical methods were
      utilized to elucidate the prevailing mechanisms for electroreduction of
      previously synthesized porphyrin-corrole dyads of the form (PCY)H2Co and
      (PCY)MClCoCl where M = Fe(III) or Mn(III), PC = porphyrin-corrole, and Y is a
      bridging group, either biphenylenyl (B), 9,9-dimethylxanthenyl (X), anthracenyl
      (A), or dibenzofuranyl (O). These studies were carried out in pyridine,
      conditions under which the cobalt(IV) corrole in (PCY)MClCoCl is immediately
      reduced to its Co(III) form, thus enabling direct comparisons with the free-base
      porphyrin dyad, (PCY)H2Co(III) under the same solution conditions. The compounds
      are all reduced in multiple one-electron-transfer steps, the first of which
      involves the M(III)/M(II) process of the porphyrin in the case of (PCY)MClCoCl
      and the Co(III)/Co(II) process of the corrole in the case of (PCY)H2Co. Each
      metal-centered redox reaction may be accompanied by the gain or loss of pyridine
      axial ligands, with the exact stoichiometry of the exchange process depending
      upon the specific combination of metal ions in the dyad, their oxidation states,
      and the particular spacer in the complex. Before this study was started, it was
      expected that the porphyrin-corrole dyads with the largest spacers, namely, O and
      A, would readily accommodate the formation of cobalt(III) bis-pyridine adducts
      because of the larger size of the cavity while dyads with the smallest B spacer
      would seem to have insufficient room to add even a single pyridine within the
      cavity, as was structurally seen in the case of (PCB)H2Co(py). This is clearly
      not the case, as shown in the present study. A reversible Co(III)/Co(II) reaction
      is seen for (PCB)MnClCoCl at -0.62 V, which when combined with spectroscopic
      data, leads to the assignment of (PCB)Mn(III)(py)2Co(III)(py) as the species in
      pyridine. The reduction of (PCB)Mn(III)(py)2Co(III)(py) to
      (PCB)Mn(II)(py)Co(III)(py) is accompanied on the slower spectroelectrochemical
      time scale by the appearance of a 603 nm band in the UV-vis spectra and is
      consistent with the addition of a second pyridine ligand to the Co(III)(py) unit
      of the dyad as one ligand is lost from the electrogenerated manganese(II)
      porphyrin, thus maintaining one pyridine ligand within the cavity. A different
      change in the coordination number is observed in the case of (PCB)FeClCoCl. Here
      the initial Fe(III) complex can be assigned as (PCB)Fe(III)ClCo(III)(py), which
      has no pyridine molecule within the cavity and the singly reduced form is
      characterized as (PCB)Fe(II)(py)2Co(III)(py)2, which contains two pyridine
      ligands inside the cavity. A following one-electron reduction of the
      Fe(II)/Co(III) complex then gives [(PCB)Fe(II)(py)2Co(II)]-.

PMID- 16296859
TI  - One-dimensional azido-bridged chiral metal complexes with ferromagnetic or
      antiferromagnetic interactions: syntheses, structures, and magnetic studies.
AB  - One-dimensional chiral copper(II) and manganese(II) coordination polymers with
      single asymmetric end-to-end (EE) azide bridges, [Cu(R-L)2(N3)]n(ClO4)n (1),
      [Cu(S-L)2 (N3)]n(ClO4)n (2), [Mn(R-L)2(N3)]n(ClO4)n (3), and [Mn(S
      L)2(N3)]n(ClO4)n (4) (R-L or S-L = R- or S-pyridine-2-carbaldehyde-imine), have
      been synthesized, using azide ions as bridging groups and chiral Schiff bases as
      auxiliary ligands, and characterized. The crystal structure determination of
      complexes 1 and 2 reveals the formation of one-dimensional chiral chains, in
      which the central Cu(II) ion is six-coordinate in the form of an elongated
      octahedron. Complex 3 consists of chiral helical polymeric chains, in which the
      central Mn(II) has a slightly distorted octahedral geometry. They all crystallize
      in the chiral space group P2(1). Complexes 1 and 2 are rare examples that exhibit
      ferromagnetic interaction between copper(II) ions through the single end-to-end
      azido bridge. Fitting the susceptibility data for 1 using a 1D uniform chain
      model led to the parameters J = 0.70(3) cm(-1), g = 2.06(2), and zj' = 0.07(2)
      cm(-1). The magnetic studies on 3 and 4 show that there is weak antiferromagnetic
      coupling between the manganese(II) ions.

PMID- 16296860
TI  - Lanthanide borohydride complexes supported by diaminobis(phenoxide) ligands for
      the polymerization of epsilon-caprolactone and L- and rac-lactide.
AB  - Reaction of Na2O2NN' [H2O2NN' = (2-C5H4N)CH2N[2-HO-3,5-C6H2(t)Bu2]2] with
      M(BH4)3(THF)3 afforded the dimeric, rare-earth borohydride compounds [M(O2NN')(mu
      BH4)(THF)n]2 [M = Y(III), n = 0.5 (1-Y); M = NdIII, n = 1 (1-Nd); M = SmIII, n =
      0 (1-Sm)]. For comparison the chloride analogues [M(O2NN')(mu-Cl)(THF)n]2 (2-M; M
      = La(III) or Sm(III), n = 0; M = Nd(III), n = 1) and the corresponding pyridine
      adducts [M(O2NN')(mu-X)(py)]2 [X = BH4 (3-M) or Cl (4-M); M = La(III), Nd(III),
      or Sm(III)] were prepared and structurally characterized for 4-La. Compounds 1-M
      initiated the ring-opening polymerization of epsilon-caprolactone. The best
      molecular weight control (suppression of chain transfer) for all three monomers
      was found for the samarium system 1-Sm. The most effective heterotactic
      enrichment (Pr) in the polymerization of rac-lactide was found for 1-Y (P(r) =
      87%). Compound 1-Nd catalyzed the block copolymerization of epsilon-caprolactone
      and L- and rac-lactide provided that epsilon-caprolactone was added first.
      Attempted block polymerization by the addition of L-lactide first, or random
      copolymerization of a ca. 1:1 mixture of epsilon-caprolactone and L-lactide, gave
      only a poly(L-lactide) homopolymer.

PMID- 16296861
TI  - UV-Vis, NMR, and time-resolved spectroscopy analysis of photoisomerization
      behavior of three- and six-azobenzene-bound tris(bipyridine)cobalt complexes.
AB  - The photoisomerization properties of tris(bipyridine)cobalt complexes containing
      six or three azobenzene moieties, namely, [Co(II)(dmAB)3](BF4)2 [dmAB = 4,4'
      bis[3''-(4'''-tolylazo)phenyl]-2,2'-bipyridine], [Co(III)(dmAB)3](BF4)3,
      [Co(II)(mAB)3](BF4)2 [mAB = 4-[3' '-(4' ''-tolylazo)phenyl]-2,2'-bipyridine], and
      [Co(III)(dmAB)3](BF4)3, derived from the effect of gathering azobenzenes in one
      molecule and the effect of the cobalt(II) or cobalt(III) ion were investigated
      using UV-vis absorption spectroscopy, femtosecond transient spectroscopy, and 1H
      NMR spectroscopy. In the photostationary state of these four complexes, nearly
      50% of the trans-azobenzene moieties of the Co(II) complexes were converted to
      the cis isomer, and nearly 10% of the trans-azobenzene moieties of the Co(III)
      complexes isomerized to the cis isomer, implying that the cis isomer ratio in the
      photostationary state upon irradiation at 365 nm is controlled not by the number
      of azobenzene moieties in one molecule but rather by the oxidation state of the
      cobalt ions. The femtosecond transient absorption spectra of the ligands and the
      complexes suggested that the photoexcited states of the azobenzene moieties in
      the Co(III) complexes were strongly deactivated by electron transfer from the
      azobenzene moiety to the cobalt center to form an azobenzene radical cation and a
      Co(II) center. The cooperation among the photochemical structural changes of six
      azobenzene moieties in [Co(II)(dmAB)3](BF4)2 was investigated with 1H NMR
      spectroscopy. The time-course change in the 1H NMR signals of the methyl protons
      indicated that each azobenzene moiety in [Co(II)(dmAB)3](BF4)2 isomerized to a
      cis isomer with a random probability of 50% and without interactions among the
      azobenzene moieties.

PMID- 16296862
TI  - Reactivity of bis(mu-hydroxo) divanadium site in gamma-H2SiV2W10O40(4-) with
      hydroxo compounds.
AB  - The reactivity of divanadium-substituted silicotungstate, gamma-H2SiV2W10O40(4-)
      (I), with hydroxo compounds of alcohols, carboxylic acids, and water is reported.
      The reaction of the bis(mu-hydroxo) divanadium site in I with primary alcohols
      and formic acid smoothly proceeds to form corresponding monoesters and
      monoformate, respectively, and the crystal structures of the monomethyl and
      monoethyl esters and the monoformate of I are determined. The oxygen exchange
      between the hydroxo group and water proceeds easily. On the other hand, bulky
      compounds of 2-propanol, tert-butyl alcohol, and acetic acid hardly react with
      the bis(mu-hydroxo) divanadium site (equilibrium constant < 0.01) because of the
      steric crowding between the methyl groups and the polyoxometalate framework.

PMID- 16296863
TI  - Infrared spectra and structures of the coinage metal dihydroxide molecules.
AB  - Laser-ablated Cu, Ag, and Au atoms react with H2O2 and with H2 + O2 molecules
      during condensation in excess argon to give four new IR absorptions in each
      system (O-H stretch, M-O-H bend, O-M-O stretch, and M-O-H deformation modes) that
      are due to the coinage metal M(OH)2 dihydroxide molecules. Isotopic substitution
      (D2O2, 18O2, 16O18O, D2, and HD) and comparison with frequencies computed by DFT
      verify these assignments. The calculations converge to 2B(g) ground electronic
      state structures with C2h symmetry, 111-117 degrees M-O-H bond angles, and
      substantial covalent character for these new metal dihydroxide molecules,
      particularly for Au(OH)2. This is probably due to the high electron affinity of
      gold owing to the effect of relativity.

PMID- 16296864
TI  - Novel hydridoirida-beta-diketones containing small molecules, CO, or ethylene:
      their behavior in coordinating solvents such as dimethylsulfoxide or
      acetonitrile.
AB  - New hydridoirida-beta-diketones [IrH[(PPh2(o-C6H4CO))2H](CO)]ClO4 2 and
      [IrH[(PPh2(o-C6H4CO))2H](olefin)]BF4 (olefin = C2H4, 5; 1-hexene, 10) have been
      prepared. These complexes may afford new diacylhydridoiridium(III) derivatives.
      In chloroform solution, complex 2 is in equilibrium with the deprotonated
      diacylhydride trans-[IrH(PPh2(o-C6H4CO))2(CO)] complex 3. In DMSO, deprotonation
      of 2 occurs to yield the kinetically favored product 3, which isomerizes to the
      thermodynamically favored complex cis-[IrH(PPh2(o-C6H4CO))2(CO)] 4. Reprotonation
      of 4 with HBF4 in chlorinated solvents gives the cation in 2. In coordinating
      solvents such as dimethyl sulfoxide or acetonitrile, complex 5 undergoes
      displacement of ethylene to afford [IrH{(PPh2(o-C6H4CO))2H](L)]BF4 (L = DMSO, 7;
      CH3CN, 9). Complexes 5 and 7 undergo deprotonation by NEt3 to give the
      corresponding diacylhydrides. The ethylene complex gives only trans-[IrH(PPh2(o
      C6H4CO))2(C2H4)] 6, while the dimethyl sulfoxide derivative affords a mixture of
      trans- and cis-[IrH(PPh2(o-C6H4CO))2(DMSO)] 8. Complex 10 shows inhibited alkene
      rotation around the Ir-olefin axis. All of the complexes were fully characterized
      spectroscopically. Single-crystal X-ray diffraction analysis was performed on
      complexes 3, 4, and 9. The 13C NMR and X-ray data point to a carbenoid character
      in the carbon atoms bonded to iridium in the irida--diketone fragment, so that it
      can be considered as an acyl(hydroxycarbene) moiety.

PMID- 16296865
TI  - Vertex-linked ZnO2S2 tetrahedra in the oxysulfide BaZnOS: a new coordination
      environment for zinc in a condensed solid.
AB  - The wide-band-gap semiconductor BaZnOS adopts a high-symmetry modification of the
      SrZnO2 structure type and contains layers of vertex-linked ZnO2S2 tetrahedra,
      which represent a novel coordination environment for zinc in the solid state.
      BaZnOS: orthorhombic, space group Cmcm; a = 3.9619(2) angstroms, b = 12.8541(7)
      angstroms, c = 6.1175(4) angstroms, Z = 4. Diffuse-reflectance spectroscopy
      measurements reveal a direct band gap of 3.9(3) eV, consistent with the white
      color and the results of band structure calculations. The band gap is larger than
      those observed in ZnO and ZnS, consistent with the more ionic nature of BaZnOS.
      Attempts to dope this compound electronically have so far not proved possible.

PMID- 16296866
TI  - Multinuclear and dynamic NMR study of trans-[Pt(Cl)(PHCy2)2(PCy2)],
      [Pt(Cl)(PHCy2)3][BF4], [Pt(Cl)(PHCy2)3][Cl], trans-[Pt(Cl)(PHCy2)2[P(S)Cy(2)]],
      and trans-[Pt(Cl)(PHCy2)2[P(O)Cy2]]. Influence of intramolecular P=O...H-P and
      Cl...H-P interactions on restricted rotation about Pt-P bond. X-ray structure of
      trans-[Pt(Cl)(PHCy2)2[P(O)Cy2]].
AB  - Dynamic NMR experiments on trans-[Pt(Cl)(PHCy2)2[P(X)Cy2]]z where X is a lone
      pair (1, z = 0), H (2, z = +1), S (3, z = 0), or O (4, z = 0) show that the
      rotation around the P(X)-Pt bond is hindered for all molecules studied, with
      deltaG++ ranging from 8.2 to 11.0 kcal/mol. The highest value of the series was
      calculated for trans-[Pt(Cl)(PHCy2)2[P(O)Cy2]] (4) where intramolecular P=O...H-P
      interactions act as a molecular brake at room temperature. Single-crystal X-ray
      diffraction confirms the presence of both intra and intermolecular P=O...H
      interactions in solid 4. In the case of [Pt(Cl)(PHCy2)3]Cl, multinuclear NMR
      analysis indicates the presence of a P-H...Cl- interaction in aromatic or
      halogenated solvents which could have also a minor effect on the rotational
      barrier around the P(X)-Pt bond.

PMID- 16296867
TI  - Physical parameters and electron-transfer kinetics of the copper(II/I) complex
      with the macrocyclic sexadentate ligand [18]aneS6.
AB  - The electron-transfer kinetics of the complex formed by copper(II/I) with the
      sexadentate macrocyclic ligand 1,4,7,10,13,16-hexathiacyclooctadecane ([18]aneS6)
      have been measured in acetonitrile with a series of three oxidizing agents and
      three reducing agents. These studies have been supplemented by determinations of
      the redox potential and the stability constants of the Cu(I)- and
      Cu(II)([18]aneS6) complexes in both acetonitrile and aqueous solution. The Marcus
      cross relationship has been applied to the cross-reaction rate constants for the
      six reactions studied to resolve the electron self-exchange rate constant for the
      Cu(II/I)([18]aneS6) complex. An average value of k11 = 3 x 10(3) M(-1) s(-1) was
      obtained at 25 degrees C, mu = 0.10 M in acetonitrile. This value is
      approximately 2 orders of magnitude smaller than the values reported previously
      for the corresponding Cu(II/I) complexes with the quadridentate and
      quinquedentate homoleptic homologues having all ethylene bridges, namely,
      1,4,7,10-tetrathiacyclododecane ([12]aneS4) and 1,4,7,10,13
      pentathiacyclopentadecane ([15]aneS5). This significant difference in reactivity
      is attributed to the greater rearrangement in the geometry of the inner
      coordination sphere that accompanies electron transfer in the Cu(II/I)([18]aneS6)
      system, wherein two Cu-S bonds are ruptured upon reduction. In contrast to other
      Cu(II/I) complexes with macrocyclic polythiaethers that have self-exchange rate
      constants within the same range, no evidence for conformationally gated electron
      transfer was observed, even in the case of the most rapid oxidation reaction
      studied.

PMID- 16296868
TI  - Tetranuclear manganese(II) complexes of thiacalixarene macrocycles with trigonal
      prismatic six-coordinate geometries: synthesis, structure, and magnetic
      properties.
AB  - Two tetranuclear manganese(II) complexes [Mn(II)4(thiaS)2] (1) and
      [Mn(II)4(thiaSO)2] (2) have been synthesized under solvothermal conditions in
      methanol with p-tert-butylthiacalix[4]arene (thiaS) and p-tert
      butylsulfinylthiacalix[4]arene (thiaSO). For both complexes, the structure has
      been established from single-crystal X-ray diffraction. [Mn4(thiaS)2].H2O (1)
      crystallizes in the orthorhombic Immm (No. 71) space group with the following
      parameters: a = 18.213 (5) angstroms, b = 19.037 (5) angstroms, c = 29.159 (5)
      angstroms, V = 10110 (4) angstroms3, and Z = 4. [Mn4(thiaSO)2].H2O (2)
      crystallizes in the monoclinic C2/m (No. 12) space group with the following
      parameters: a = 33.046(1) angstroms, b = 19.5363 (8) angstroms, c = 15.7773 (9)
      angstroms, beta = 115.176 (2) degrees, V = 9218.3 (8) angstroms3, and Z = 4. The
      two complexes are neutral and are best described as manganese squares sandwiched
      between two thiacalixarene macrocycles. In both complexes, each manganese center
      is six-coordinated in a trigonal prismatic geometry with four phenoxo oxygen
      atoms plus two sulfur atoms for 1 or two oxygen atoms from SO groups for 2. The
      two tetranuclear complexes exhibit identical magnetic behaviors resulting from
      antiferromagnetic interactions between the four manganese centers. The simulation
      of the magnetic susceptibility was done considering a single exchange-coupling
      constant between the manganese(II) ions, J (H = -J(S1S2 + S2S3 + S3S4 + S1S4)).
      The best fits give the same result for the two complexes: g = 1.94 and J = -5.57
      cm(-1).

PMID- 16296869
TI  - Defining the role of mycophenolate mofetil in the treatment of proliferative
      lupus nephritis.
AB  - Systemic lupus erythematosus, which predominantly affects young women, is
      frequently complicated by renal involvement. The presence of acute
      glomerulonephritis significantly adds to morbidity and mortality.
      Cyclophosphamide has become the mainstay of treatment in patients with
      proliferative forms of lupus nephritis. However, adverse events such as severe
      infections and infertility have spurred the search for novel treatment regimens
      and agents. Sequential therapy has significantly reduced adverse events. In
      several pilot studies, mycophenolate mofetil (MMF) has emerged as a promising
      therapeutic approach for both the induction and maintenance phase in patients
      with lupus nephritis, delivering equal efficacy and a better adverse effect
      profile; however, these studies had a limited power, and a large, multicentre and
      probably multinational clinical trial will be needed to discern the optimal
      therapeutic approach. On the basis of the currently available literature,
      sequential therapy with cyclophosphamide induction followed by azathioprine or
      MMF maintenance can be recommended for most patients. In selected populations,
      induction with MMF is a reasonable option to reduce adverse events.

PMID- 16296870
TI  - Tuberculosis vaccines: current progress.
AB  - Tuberculosis continues to be a major cause of disease and death throughout the
      developing world. Chemotherapy is the current method of control but with the
      continuing emergence of drug resistance, coupled with the reticence of major drug
      companies to invest in drug discovery, the identification of new vaccines to
      combat tuberculosis is a pressing need. Rational vaccine design requires
      knowledge of the protective immune response and, while this is not fully
      understood, it is clear that induction of a T-helper-1 type of immunity is
      critical to host resistance. A variety of animal models, but especially the mouse
      and guinea pig, can be used to determine the protective efficacy of new vaccines.
      These mostly consist of relatively short-term prophylactic models in which
      animals are vaccinated and then challenged by the aerosol infection route to
      determine their capacity to reduce the lung bacterial load. Several promising
      vaccine types have emerged, including subunit vaccines, DNA vaccines and vaccines
      based upon living vectors, such as recombinant bacillus Calmette-Guerin (BCG)
      vaccines and auxotrophic or gene disrupted mutants of Mycobacterium tuberculosis.
      A few of these have already entered early stage clinical trials.

PMID- 16296872
TI  - Issues for clinical drug development in neurodegenerative diseases.
AB  - Neurodegenerative diseases pose specific challenges for drug development. These
      diseases typically have a slow and variable clinical course, an insidious onset,
      and symptom expression is only observed when a significant proportion of neurons
      are already lost. It is important to identify vulnerability factors and other
      determinants of clinical course in order to be able in the future to select
      patient populations for clinical trials with a predictable prognosis. The
      neurodegenerative process itself is not amenable to direct observation and, thus,
      cannot be monitored in clinical trials. For this reason, surrogate biomarkers are
      required for use as outcome parameters. In this respect, magnetic resonance
      imaging has proved valuable for assessing disease activity and progression in
      multiple sclerosis. Rating scales are of use as outcome measures but, as these
      generally measure symptom severity, they are most appropriate for use in
      assessing symptomatic treatments. Survival has been used with success as an
      outcome measure in trials in amyotrophic lateral sclerosis, where disease
      progression is rapid. The optimal outcome measure, the sample size required and
      the treatment duration need to be chosen in relation to the phase of the disease.
      Potential new treatments can be chosen based upon new knowledge of the genetics
      and physiopathology of neurodegenerative diseases and, in some cases, screened in
      transgenic mouse models, although it should be recognised that the validity of
      these models in terms of treatment response has yet to be established
      empirically.

PMID- 16296871
TI  - Pathophysiological basis for antioxidant therapy in chronic liver disease.
AB  - Oxidative stress is a common pathogenetic mechanism contributing to initiation
      and progression of hepatic damage in a variety of liver disorders. Cell damage
      occurs when there is an excess of reactive species derived from oxygen and
      nitrogen, or a defect of antioxidant molecules. Experimental research on the
      delicately regulated molecular strategies whereby cells control the balance
      between oxidant and antioxidant molecules has progressed in recent years. On the
      basis of this evidence, antioxidants represent a logical therapeutic strategy for
      the treatment of chronic liver disease. Clinical studies with large numbers of
      patients have not yet been performed. However, results from several pilot trials
      support this concept and indicate that it may be worth performing multicentre
      studies, particularly combining antioxidants with anti-inflammatory and/or
      antiviral therapy. Oxidative stress plays a pathogenetic role in liver diseases
      such as alcoholic liver disease, chronic viral hepatitis, autoimmune liver
      diseases and non-alcoholic steatohepatitis. The use of antioxidants (e.g. S
      adenosylmethionine [SAMe; ademetionine], tocopherol [vitamin E],
      polyenylphosphatidylcholine or silymarin) has already shown promising results in
      some of these pathologies.

PMID- 16296873
TI  - Parathyroid hormone as an anabolic skeletal therapy.
AB  - The quest for effective treatment for osteoporosis merits great attention because
      of the widespread prevalence of this disease, which is not only associated with
      fragility fractures, but also with significant morbidity and mortality. The
      efficacy of the antiresorptive drugs in this disease is achieved by reducing bone
      turnover, increasing bone density and improving other aspects of bone quality.
      This article concentrates on another approach to the treatment of osteoporosis,
      namely the use of anabolic therapy, which has even greater prospects for
      improving bone quality. Parathyroid hormone (PTH) is currently available only as
      the recombinant amino-terminal fragment, PTH(1-34), known as teriparatide. The
      full-length molecule, human PTH(1-84), is currently being investigated, as are
      other PTH molecules. Teriparatide improves bone quality through actions on bone
      turnover, bone density, bone size and bone microarchitecture. In postmenopausal
      women with osteoporosis, teriparatide reduces the incidence of vertebral and
      nonvertebral fractures. In individuals who have previously been treated with an
      antiresorptive agent, the subsequent actions of teriparatide on bone density are
      transiently delayed if bone turnover has been markedly suppressed. Combination
      therapy with teriparatide or PTH(1-84) and an antiresorptive agent does not
      appear, at this time, to offer advantages over the use of PTH or an
      antiresorptive agent alone. However, in order to maintain the densitometric gains
      in bone density obtained with PTH, it is important to follow its use with that of
      an antiresorptive agent.

PMID- 16296874
TI  - Continuous versus intermittent intravenous administration of antibacterials with
      time-dependent action: a systematic review of pharmacokinetic and pharmacodynamic
      parameters.
AB  - We performed a systematic review of randomised clinical trials to evaluate the
      comparative pharmacokinetic and pharmacodynamic properties of the continuous
      versus intermittent mode of intravenous administration of various antibacterials.
      Data were identified from PubMed (January 1950 to January 2005), Current
      Contents, the Cochrane central register of controlled trials, and references from
      relevant articles and reviews. Seventeen randomised clinical trials comparing
      continuous with intermittent intravenous administration of the same antibacterial
      regimen and examining the pharmacokinetic and pharmacodynamic properties were
      included in this systematic review. We reviewed data regarding the clinical
      setting, number of participants, antibacterial agents and dosages used, as well
      as maximum serum concentration (Cmax), trough serum concentration (Cmin), steady
      state or plateau serum concentration (Css), area under the concentration-time
      curve (AUC), time above the minimum inhibitory concentration (MIC) [T>MIC], AUC:
      MIC, elimination rate constant, elimination half-life, volume of distribution and
      systematic clearance. The mean Cmax of the intermittently administered
      antibacterials was higher compared with Css achieved by the continuous infusion
      of the same antibacterial in all eligible studies (Cmax was on average 5.5 times
      higher than Css, range 1.9-11.2). Css was on average 5.8 times higher than the
      Cmin of the intermittently administered antibacterials (range 1.2-15.6). In three
      of six studies the length of time that the drug concentration was above the MIC
      of the responsible pathogens was longer in patients receiving the antibacterials
      continuously. In conclusion, the reviewed data suggest that the continuous
      intravenous infusion of antibacterials with time-dependent bacterial killing
      seems to be superior than the intermittent intravenous administration, from a
      pharmacodynamic point of view, at least when treating bacteria with high MIC
      values for the studied antibacterials.

PMID- 16296875
TI  - Docetaxel: a review of its use in metastatic breast cancer.
AB  - Docetaxel (Taxotere), a cytotoxic taxane, is an antimicrotubule agent effective
      in the treatment of patients with breast cancer. The clinical profile of
      docetaxel as an effective cytotoxic agent in the treatment of metastatic breast
      cancer is well established. As yet, no single standard regimen has been
      identified as optimal for the treatment of patients with metastatic breast cancer
      after failure of prior chemotherapy. However, the efficacy of docetaxel
      monotherapy administered every 3 weeks as a 1-hour infusion is similar to or
      better than that of doxorubicin, paclitaxel and fluorouracil plus vinorelbine,
      and better than that of methotrexate plus fluorouracil or mitomycin plus
      vinblastine. Although docetaxel is associated with neutropenia and other adverse
      events, its overall tolerability profile is generally acceptable in the majority
      of patients. Docetaxel, therefore, is an effective option in the treatment of
      patients with metastatic breast cancer after failure of prior chemotherapy.

PMID- 16296877
TI  - A bystander effect in alpha-particle irradiations of human prostate tumor cells.
AB  - Alpha-particle exposures were used to determine whether cells of the human
      prostate carcinoma cell line DU-145 can produce and respond to a bystander effect
      signal. An apparatus for alpha-particle irradiation of cells growing as a
      monolayer on a 1.4-microm-thick Mylar membrane directly above an 241Am alpha
      particle source was constructed and calibrated. At the cell irradiation position,
      the alpha-particle fluence was 998 counts/mm2 s(-1), the average alpha-particle
      energy was 3.14 MeV, and the average linear energy transfer was 128 keV/microm.
      The average dose rate to the cells growing on the Mylar surface was 1.2 Gy/min. A
      co-culture system was used to examine bystander effects transmitted through the
      medium from the directly targeted cells to tumor cells growing on an insert well
      beyond the range of the alpha particles. Alpha-particle doses from 0.1 to 6.0 Gy
      to the targeted cells on the Mylar membrane, followed by a 2-h co-incubation of
      the cells on the insert in the irradiated medium above the irradiated cells, all
      caused an approximately 50% increase in micronucleus formation in the nontargeted
      co-cultured cells. Addition of the radical scavenger DMSO to the medium during
      the irradiation and the 2-h postirradiation incubation period completely blocked
      the bystander effect, whereas addition of a nitric oxide scavenger had no effect.
      Irradiation of medium containing serum, followed by a 2-h incubation, caused no
      bystander effect in the co-cultured cells. When the co-cultured cells on the
      insert were placed into the irradiated medium above the directly targeted cells
      immediately (approximately 1 min) after the irradiation and co-incubated for 2 h,
      there was no bystander effect. These data indicate that the observed bystander
      effect requires that the co-cultured cells be present in the medium during the
      irradiation of the directly targeted cells and suggest the involvement of a short
      lived radical species.

PMID- 16296876
TI  - Quetiapine: a review of its use in acute mania and depression associated with
      bipolar disorder.
AB  - Quetiapine (Seroquel), an atypical antipsychotic with established efficacy in the
      treatment of schizophrenia, shows efficacy in the treatment of acute mania and
      depression associated with bipolar disorder.Quetiapine, either as monotherapy or
      in combination with lithium or divalproex sodium (valproate semisodium), is
      generally well tolerated and effective in reducing manic symptoms in adult and
      adolescent patients with acute bipolar mania, and is approved for use in adults
      for this indication. As monotherapy, the drug is also effective in reducing
      depressive symptoms in patients with bipolar depression. It is associated with a
      low incidence of extrapyramidal symptom (EPS)-related adverse events and low EPS
      ratings in bipolar disorder. Quetiapine thus shows potential in the treatment of
      bipolar depression, and represents a useful agent for the treatment of acute
      bipolar mania.

PMID- 16296878
TI  - Effect of nitric oxide on gamma-ray-induced micronucleus frequency in RAW264.7
      cells.
AB  - The effect of low-dose nitric oxide (NO) on gamma-ray-induced micronucleus (MN)
      frequency was investigated in RAW264.7 cells. Treatment of RAW264.7 cells with
      0.25 mM sodium nitroprusside (SNP), a chemical NO donor, reduced the frequency of
      micronuclei induced by 5 Gy gamma rays by 43 to 45% between 3 and 12 h post
      treatment. This effect was blocked by carboxy-PTIO, suggesting that NO may play a
      role in the reduction of radiation-induced MN frequency. To examine possible
      mechanisms underlying this effect, we first looked at changes in the antioxidant
      system after SNP treatment. A significant increase in intracellular glutathione
      (GSH) was seen in SNP-treated cells between 3 and 12 h post-treatment. Depletion
      of GSH with buthionine sulfoximine (BSO) increased the gamma-ray-induced increase
      in MN frequency. Detailed studies using various inducers of intracellular GSH
      suggested that GSH induction has a partial role in the reducing effect of NO on
      the gamma-ray-induced MN frequency. Next, the effect of NO on DNA repair and
      replication systems was examined. Wortmannin, an inhibitor of DNA-dependent
      protein kinase (DNA-PK), dose-dependently inhibited the reducing effect of NO,
      while caffeine, an inhibitor of ATM kinase and ATR kinase, did not. DNA-PK
      activity was increased by NO treatment. Etoposide, a topoisomerase II inhibitor,
      dose-dependently blocked the effect of NO in reducing the gamma-ray-induced MN
      frequency. These results suggest that the mechanisms of the effect of NO on the
      gamma-ray-induced MN frequency include elevation of GSH and up-regulation of DNA
      PK activity for repairing double-strand breaks. NO may act as a signal for repair
      systems, e.g. for nonhomologous recombination and for the replication system in S
      phase, to reduce the MN frequency.

PMID- 16296879
TI  - Growth of V79 cells as xenograft tumors promotes multicellular resistance but
      does not increase spontaneous or radiation-induced mutant frequency.
AB  - A Chinese hamster V79 xenograft model was developed to determine whether cells
      subjected to a hypoxic tumor microenvironment would be more likely to undergo
      mutation at the HPRT locus. V79-171b cells stably transfected with VEGF and EGFP
      were grown subcutaneously in immunodeficient NOD/ SCID mice. V79-VE tumors were
      characterized for host cell infiltration, doubling time, hypoxic fraction,
      vascular perfusion, and response to ionizing radiation. When irradiated in vitro,
      the mutant frequency for a given surviving fraction did not differ for cells
      grown in vivo or in vitro. Similar results were obtained using HCT116 human
      colorectal carcinoma cells grown as xenografts. However, V79-VE cells grown as
      xenografts were significantly more resistant to killing than monolayers. The
      background mutant frequency and the radiation-induced mutant frequency did not
      differ for tumor cells close to or distant from blood vessels. Similarly, tumor
      cells from well-perfused regions showed the same rate of strand break rejoining
      and the same rate of loss of phosphorylated histone H2AX as cells sorted from
      poorly perfused regions. Therefore, deleterious effects of the tumor
      microenvironment on DNA repair efficiency or mutation induction could not be
      demonstrated in these tumors. Rather, development of multicellular resistance in
      V79-VE tumors acted to reduce mutant frequency for a given dose of radiation.

PMID- 16296880
TI  - Isolation and characterization of highly radioresistant malignant hamster
      fibroblasts that survive acute gamma irradiation with 20 Gy.
AB  - To study the acquired radioresistance of tumor cells, a model system of two cell
      lines, Djungarian hamster fibroblasts (DH-TK-) and their radioresistant progeny,
      was established. The progeny of irradiated cells were isolated by treating the
      parental cell monolayer with a single dose of 20 Gy (PIC-20). The genetic and
      morphological features, clonogenic ability, radiosensitivity, cell growth
      kinetics, ability to grow in methylcellulose, and tumorigenicity of these cell
      lines were compared. The plating efficiency of PIC-20 cells exceeded that of DH
      TK- cells. The progeny of irradiated cells were more radioresistant than parental
      cells. The average D0 for PIC-20 cells was 7.4 +/- 0.2 Gy, which is three times
      higher than that for parental cells (2.5 +/- 0.1 Gy). Progeny cell survival in
      methylcellulose after irradiation with a dose of 10 Gy was 15 times higher than
      that of DH-TK- cells. In contrast to parental cells, the progeny of irradiated
      cells showed fast and effective repopulation after irradiation with doses of 12.5
      and 15 Gy. The tumor formation ability of irradiated progeny cells was higher
      than that of parental cells; after 15 Gy irradiation, PIC-20 cells produced
      tumors as large as unirradiated progeny of irradiated cells, whereas the tumor
      development of DH-TK- cells diminished by 70%. High radioresistance of progeny of
      irradiated cells was reproduced during the long period of cultivation (more than
      80 passages). The stability of the radioresistant phenotype of PIC-20 cells
      allows us to investigate the possible mechanisms of acquired tumor
      radioresistance.

PMID- 16296881
TI  - Spatial distribution of radiation-induced double-strand breaks in plasmid DNA as
      resolved by atomic force microscopy.
AB  - Atomic force microscopy (AFM) has been used to directly visualize, size and
      compare the DNA fragments resulting from exposure to low- and high-LET radiation.
      Double-stranded pUC-19 plasmid ("naked") DNA samples were irradiated by electron
      beam or reactor neutron fluxes with doses ranging from 0.9 to 10 kGy. AFM
      scanning in the tapping mode was used to image and measure the DNA fragment
      lengths (ranging from a few bp up to 2864 bp long). Double-strand break (DSB)
      distributions resulting from high-LET neutron and lower-LET electron irradiation
      revealed a distinct difference between the effects of these two types of
      radiation: Low-LET radiation-induced DSBs are distributed more uniformly along
      the DNA, whereas a much larger proportion of neutron-induced DSBs are distributed
      locally and densely. Furthermore, comparisons with predictions of a random DSB
      model of radiation damage show that neutron-induced DSBs deviate more from the
      model than do electron-induced DSBs. In summary, our high-resolution AFM
      measurements of radiation-induced DNA fragment-length distributions reveal an
      increased number of very short fragments and hence clustering of DSBs induced by
      the high-LET neutron radiation compared with low-LET electron radiation and a
      random DSB model prediction.

PMID- 16296882
TI  - DNA breakage by decay of Auger electron emitters: experiments with 123I
      iodoHoechst 33258 and plasmid DNA.
AB  - The Auger electron-emitting isotope 123I is of interest in the context of
      potential exploitation of Auger electron emitters in radioimmunotherapy. The
      efficiency of induction of cytotoxic lesions by decay of DNA-associated 125I, the
      prototype Auger electron emitter, is well established, but its long half-life (60
      days) is a limitation. However, the advantage of the much shorter half-life of
      123I (13.2 h) might be outweighed by its "weaker" Auger electron cascade with an
      average of 8-11 Auger electrons, compared to about 15-21 electrons for 125I.
      Accordingly, the efficiency of DNA breakage for DNA-associated 123I was
      investigated by incubation of 123I-iodoHoechst 33258 with plasmid DNA. The
      efficiency of double-strand break induction by decay of 123I was 0.62 compared to
      0.82 per decay of 125I in the same experimental system. In the presence of
      dimethylsulfoxide, the values were 0.54 and 0.65 for decay of 123I and 125I,
      respectively. The results also showed that at a very low ligand/plasmid molar
      ratio (<1), the majority of cleavage seemed to occur at a particular site on the
      plasmid molecule, indicating preferential binding of the 123I-ligand to a unique
      site or a cluster of neighboring sites.

PMID- 16296883
TI  - High-LET irradiation of a DNA-binding protein: protein-protein and DNA-protein
      crosslinks.
AB  - The chromosomal protein MC1 is a monomeric protein of 93 amino acids that is able
      to bind any DNA but has a slight preferential affinity for some sequences and
      structures, like cruciform and minicircles. The protein has been irradiated with
      36Ar18+ ions of 95 MeV/nucleon. The LET of these particles in water is close to
      270 keV/microm. We tested the activity of the protein by measuring its ability to
      form complexes with DNA. We tested the integrity of the protein by measuring the
      molecular weight of the species formed. Compared with gamma radiation, we
      observed for the same dose a less efficient inactivation of the protein, a
      greater protection of the protein by the bound DNA, a lower induction of chain
      breakage, and a greater production of protein-protein and DNA-protein crosslinks.
      The results are discussed in terms of the quantitative and the qualitative
      differences between the two types of radiation: The global radical yield is
      slightly higher with gamma rays, whereas the density of radicals produced along
      the particle track is considerably higher with argon ions.

PMID- 16296884
TI  - DNA strand breaks signal the induction of DNA double-strand break repair in
      Saccharomyces cerevisiae.
AB  - Genotoxic stress induces a checkpoint signaling cascade to generate a stress
      response. Saccharomyces cerevisiae shows an altered radiation response under
      different type of stress. Although the induction of repair has been implicated in
      enhanced survival after exposure to the challenging stress, the nature of the
      signal remains poorly understood. This study demonstrates that low doses of gamma
      radiation and bleomycin induce RAD52-dependent recombination repair pathway in
      the wild-type strain D-261. Prior exposure of cells to DNA-damaging agents (gamma
      radiation or bleomycin) equips them better for the subsequent damage caused by
      challenging doses. However, exposure to UV light, which does not cause strand
      breaks, was ineffective. This was confirmed by PFGE studies. This indicates that
      the strand breaks probably serve as the signal for induction of the recombination
      repair pathway while pyrimidine dimers do not. The nature of the induced repair
      was investigated by mutation scoring in special strain D-7, which showed that the
      induced repair is essentially error free.

PMID- 16296885
TI  - Evaluating DNA damage in rodent brain after acute 60 Hz magnetic-field exposure.
AB  - In recent years, numerous studies have reported a weak association between 60 Hz
      magnetic-field exposure and the incidence of certain cancers. To date, no
      mechanism to explain these findings has been identified. The objective of the
      current study was to investigate whether acute magnetic-field exposure could
      elicit DNA damage within brain cells from both whole brain and cerebellar
      homogenates from adult rats, adult mice and immature mice. Rodents were exposed
      to a 60 Hz magnetic field (0, 0.1, 1 or 2 mT) for 2 h. Then, at 0, 2 and 4 h
      after exposure, animals were killed humanely, their brains were rapidly removed
      and homogenized, and cells were cast into agarose gels for processing by the
      alkaline comet assay. Four parameters (tail ratio, tail moment, comet length and
      tail length) were used to assess DNA damage for each comet. For each species, a
      significant increase in DNA damage was detected by each of the four parameters in
      the positive control (2 Gy X rays) relative to the concurrent nonirradiated
      negative and sham controls. However, none of the four parameters detected a
      significant increase in DNA damage in brain cell homogenates from any magnetic
      field exposure (0- 2 mT) at any time after exposure. The dose-response and time
      course data from the multiple animal groups tested in this study provide no
      evidence of magnetic-field-induced DNA damage.

PMID- 16296886
TI  - Electromagnetic fields from mobile phones do not affect the inner auditory system
      of Sprague-Dawley rats.
AB  - The auditory system is the first biological structure facing the electromagnetic
      fields emitted by mobile phones. The aim of this study was to evaluate the
      cochlear functionality of Sprague-Dawley rats exposed to electromagnetic fields
      at the typical frequencies of GSM mobile phones (900 and 1800 MHz) by distortion
      product otoacoustic emissions, which are a well-known indicator of the status of
      the cochlea's outer hair cells. A population of 48 rats was divided into exposed
      and sham-exposed groups. Three sets of four loop antennas, one for sham-exposed
      animals and two for exposed animals, were used for the local exposures. Rats were
      exposed 2 h/day, 5 days/week for 4 weeks at a local SAR of 2 W/kg in the ear.
      Distortion product otoacoustic emissions tests were carried out before, during
      and after the exposure. The analysis of the data shows no statistically
      significant differences between the audiological signals recorded for the
      different groups.

PMID- 16296887
TI  - RBE of the MIT epithermal neutron beam for crypt cell regeneration in mice.
AB  - The RBE of the new MIT fission converter epithermal neutron capture therapy (NCT)
      beam has been determined using intestinal crypt regeneration in mice as the
      reference biological system. Female BALB/c mice were positioned separately at
      depths of 2.5 and 9.7 cm in a Lucite phantom where the measured total absorbed
      dose rates were 0.45 and 0.17 Gy/ min, respectively, and irradiated to the whole
      body with no boron present. The gamma-ray (low-LET) contributions to the total
      absorbed dose (low- + high-LET dose components) were 77% (2.5 cm) and 90% (9.7
      cm), respectively. Control irradiations were performed with the same batch of
      animals using 6 MV photons at a dose rate of 0.83 Gy/min as the reference
      radiation. The data were consistent with there being a single RBE for each NCT
      beam relative to the reference 6 MV photon beam. Fitting the data according to
      the LQ model, the RBEs of the NCT beams were estimated as 1.50 +/- 0.04 and 1.03
      +/- 0.03 at depths of 2.5 and 9.7 cm, respectively. An alternative
      parameterization of the LQ model considering the proportion of the high- and low
      LET dose components yielded RBE values at a survival level corresponding to 20
      crypts (16.7%) of 5.2 +/- 0.6 and 4.0 +/- 0.7 for the high-LET component
      (neutrons) at 2.5 and 9.7 cm, respectively. The two estimates are significantly
      different (P = 0.016). There was also some evidence to suggest that the shapes of
      the curves do differ somewhat for the different radiation sources. These
      discrepancies could be ascribed to differences in the mechanism of action, to
      dose-rate effects, or, more likely, to differential sampling of a more complex
      dose-response relationship.

PMID- 16296888
TI  - A nested case-control study of leukemia mortality and ionizing radiation at the
      Portsmouth Naval Shipyard.
AB  - A nested case-control study using conditional logistic regression was conducted
      to evaluate the exposure-response relationship between external ionizing
      radiation exposure and leukemia mortality among civilian workers at the
      Portsmouth Naval Shipyard (PNS), Kittery, Maine. The PNS civilian workers
      received occupational radiation exposure while performing construction, overhaul,
      repair and refueling activities on nuclear-powered submarines. The study age
      matched 115 leukemia deaths with 460 controls selected from a cohort of 37,853
      civilian workers employed at PNS between 1952 and 1992. In addition to radiation
      doses received in the workplace, a secondary analysis incorporating doses from
      work-related medical X rays and other occupational radiation exposures was
      conducted. A significant positive association was found between leukemia
      mortality and external radiation exposure, adjusting for gender, radiation worker
      status, and solvent exposure duration (OR = 1.08 at 10 mSv of exposure; 95% CI =
      1.01, 1.16). Solvent exposure (including benzene and carbon tetrachloride) was
      also significantly associated with leukemia mortality adjusting for radiation
      dose, radiation worker status, and gender. Incorporating doses from work-related
      medical X rays did not change the estimated leukemia risk per unit of dose.

PMID- 16296889
TI  - Effects of radiation on the longitudinal trends of hemoglobin levels in the
      Japanese atomic bomb survivors.
AB  - The late effects of radiation on the hematopoietic system have not been fully
      evaluated. We examined the long-term effects of radiation exposure on hemoglobin
      levels in the Japanese atomic bomb survivors over a 40-year period from 1958 to
      1998. Compared to the unexposed survivors, the mean hemoglobin levels for those
      exposed to a bone marrow dose of 1 Gy were significantly reduced by 0.10 g/dl
      (95% CI: 0.04 to 0.16) or 0.67% at 40 years of age (P < 0.0001) and by 0.24 g/dl
      (95% CI: 0.08 to 0.40) or 1.8% at 80 years of age. Radiation effects are greater
      for smokers than for nonsmokers at age less than 35 years (P < 0.01), although
      cigarette smoking was associated with increased hemoglobin levels. Sex and birth
      cohort differences in radiation effects were not found after adjusting for
      smoking. The radiation-induced reduction in hemoglobin levels could not be
      explained by the presence of certain anemia-associated diseases.

PMID- 16296890
TI  - Comments on "Two-mutation models for bone cancer due to radium, strontium and
      plutonium" by Bijwaard et al. (Radiat. Res. 162, 171-184, 2004).

PMID- 16296892
TI  - Wolfgang Pohlit (1928-2005).

PMID- 16296894
TI  - Homeopathy, Hahnemann, and The Lancet 250 years on: a case of the emperor's new
      clothes?

PMID- 16296895
TI  - The end of biomedical journals: there is madness in their methods.

PMID- 16296896
TI  - A "Maddox effect"? A reason to adopt time series protocols in tests of
      homeopathic remedies.

PMID- 16296897
TI  - All evidence is equal, but some evidence is more equal than others: can logic
      prevail over emotion in the homeopathy debate?

PMID- 16296898
TI  - Reproductions and reproducibility in homeopathy: dogma or tool?

PMID- 16296899
TI  - The homeopathic mechanism from the viewpoint of a quantum mechanical paradoxon.

PMID- 16296893
TI  - Effects of hypothalamic neurodegeneration on energy balance.
AB  - Normal aging in humans and rodents is accompanied by a progressive increase in
      adiposity. To investigate the role of hypothalamic neuronal circuits in this
      process, we used a Cre-lox strategy to create mice with specific and progressive
      degeneration of hypothalamic neurons that express agouti-related protein (Agrp)
      or proopiomelanocortin (Pomc), neuropeptides that promote positive or negative
      energy balance, respectively, through their opposing effects on melanocortin
      receptor signaling. In previous studies, Pomc mutant mice became obese, but Agrp
      mutant mice were surprisingly normal, suggesting potential compensation by
      neuronal circuits or genetic redundancy. Here we find that Pomc-ablation mice
      develop obesity similar to that described for Pomc knockout mice, but also
      exhibit defects in compensatory hyperphagia similar to what occurs during normal
      aging. Agrp-ablation female mice exhibit reduced adiposity with normal
      compensatory hyperphagia, while animals ablated for both Pomc and Agrp neurons
      exhibit an additive interaction phenotype. These findings provide new insight
      into the roles of hypothalamic neurons in energy balance regulation, and provide
      a model for understanding defects in human energy balance associated with
      neurodegeneration and aging.

PMID- 16296900
TI  - Remembering the holistic view.

PMID- 16296901
TI  - Classifying and defining complementary and alternative medicine.

PMID- 16296902
TI  - Horton deplores breach; as do we his.

PMID- 16296903
TI  - Shang et al. carelessness, collusion, or conspiracy?

PMID- 16296904
TI  - Bias in the trial and reporting of trials of homeopathy: a fundamental breakdown
      in peer review and standards?

PMID- 16296905
TI  - Failure to exclude false negative bias: a fundamental flaw in the trial of Shang
      et al.

PMID- 16296906
TI  - Understanding placebo effects in homeopathic clinical trials.

PMID- 16296907
TI  - Sir: is that bias?

PMID- 16296909
TI  - Effects of an electric field on plasma levels of ACTH and beta-endorphin in dogs
      with tumors or spinal cord injuries.

PMID- 16296908
TI  - Calendula and thermal baths for treating a high-grade iatrogenic disability.

PMID- 16296910
TI  - Homeopathy and acupuncture teaching at the University of Sao Paulo Medical
      School: the undergraduates' attitudes.

PMID- 16296911
TI  - The case for orthomolecular medical care: a patient's plea.

PMID- 16296912
TI  - Homeopathic treatment for chronic disease: a 6-year, university-hospital
      outpatient observational study.
AB  - OBJECTIVE: The aim of this study was to assess health changes seen in routine
      homeopathic care for patients with a wide range of chronic conditions who were
      referred to a hospital outpatient department. DESIGN: This was an observational
      study of 6544 consecutive follow-up patients during a 6-year period. SETTING:
      Hospital outpatient unit within an acute National Health Service (NHS) Teaching
      Trust in the United Kingdom. PARTICIPANTS: Every patient attending the hospital
      outpatient unit for a follow-up appointment over the study period was included,
      commencing with their first follow-up attendance. MAIN OUTCOME MEASURE: Outcomes
      were based on scores on a 7-point Likert-type scale at the end of the
      consultation and were assessed as overall outcomes compared to the initial
      baseline assessments. RESULTS: A total of 6544 consecutive follow-up patients
      were given outcome scores. Of the patients 70.7% (n = 4627) reported positive
      health changes, with 50.7% (n = 3318) recording their improvement as better (+2)
      or much better (+3). CONCLUSIONS: Homeopathic intervention offered positive
      health changes to a substantial proportion of a large cohort of patients with a
      wide range of chronic diseases. Additional observational research, including
      studies using different designs, is necessary for further research development in
      homeopathy.

PMID- 16296914
TI  - Variation in Fourier transform infrared spectra of some homeopathic potencies and
      their diluent media.
AB  - OBJECTIVE: The aim of this study was to determine whether potentized homeopathic
      drugs and their diluent media differ from each other with respect to their
      Fourier transform infrared (FTIR) spectra. DESIGN: FTIR spectra of Nux vomica
      30C, Lycopodium 30C, Santonin 30C, Cina 30C, Cina 206C, Cina 1006C, and their
      diluent media 90% ethanol and Ethanol 30C were obtained in the wave number range
      of 2000-1000 cm1 at 20 degrees C. Potassium bromide powder soaked with the
      potencies, pressed into pellets, and air dried were used to measure the spectra.
      Because water structures in homeopathic potencies are thought to carry specific
      information on drug molecules and because O-H bending vibrational band (v2)
      exclusively belongs to water, the study was restricted to the bands in that wave
      number region. Alcohol has no absorption in the O-H bending region. RESULTS: The
      potencies were found to differ from each other and their diluent media in the
      number of v2 bands, their wave number (cm1), shape, and half-width (cm1) of the
      bands. CONCLUSIONS: The number and other characteristics of the v2 band represent
      the number of hydrogen-bonded water species and their hydrogen-bonding strength,
      respectively. The potencies and their diluent media therefore differ from each
      other in the number of hydrogen-bonded water species and their hydrogen-bonding
      strength. The observation that KBr pellets soaked with a potentized drug retains
      its specific spectral absorption properties simply confirms that medicated
      sucrose globules, used in homeopathic dispensing, are capable of retaining the
      therapeutic properties of the drug.

PMID- 16296913
TI  - Homeopathy for attention-deficit/hyperactivity disorder: a pilot randomized
      controlled trial.
AB  - OBJECTIVES: The aim of this study was to carry out a preliminary trial evaluating
      the effectiveness of homeopathy in the treatment of attention
      deficit/hyperactivity disorder (ADHD). DESIGN: This work was a randomized, double
      blind, placebo-controlled trial. SETTINGS/LOCATION: This study was conducted in a
      private homeopathic clinic in the Seattle metropolitan area. SUBJECTS: Subjects
      included children 6-12 years of age meeting Diagnostic and Statistical Manual of
      Mental Disorders 4th edition (DSM-IV) criteria for ADHD. INTERVENTIONS: Forty
      three subjects were randomized to receive a homeopathic consultation and either
      an individualized homeopathic remedy or placebo. Patients were seen by
      homeopathic physicians every 6 weeks for 18 weeks. OUTCOME MEASURES: Outcome
      measures included the Conner's Global Index-Parent, Conner's Global Index-
      Teacher, Conner's Parent Rating Scale-Brief, Continuous Performance Test, and the
      Clinical Global Impression Scale. RESULTS: There were no statistically
      significant differences between homeopathic remedy and placebo groups on the
      primary or secondary outcome variables. However, there were statistically and
      clinically significant improvements in both groups on many of the outcome
      measures. CONCLUSIONS: This pilot study provides no evidence to support a
      therapeutic effect of individually selected homeopathic remedies in children with
      ADHD. A therapeutic effect of the homeopathic encounter is suggested and warrants
      further evaluation. Future studies should be carried out over a longer period of
      time and should include a control group that does not receive the homeopathic
      consultation. Comparison to conventional stimulant medication for ADHD also
      should be considered.

PMID- 16296915
TI  - Research on homeopathy: state of the art.
AB  - In this paper, we review research on homeopathy from four perspectives, focusing
      on reviews and some landmark studies. These perspectives are laboratory studies,
      clinical trials, observational studies, and theoretical work. In laboratory
      models, numerous effects and anomalies have been reported. However, no single
      model has been sufficiently widely replicated. Instead, researchers have focused
      on ever-new models and experiments, leaving the picture of scattered anomalies
      without coherence. Basic research, trying to elucidate a purported difference
      between homeopathic remedies and control solutions has also produced some
      encouraging results, but again, series of independent replications are missing.
      While there are nearly 200 reports on clinical trials, few series have been
      conducted for single conditions. Some of these series document clinically useful
      effects and differences against placebo and some series do not. Observational
      research into uncontrolled homeopathic practice documents consistently strong
      therapeutic effects and sustained satisfaction in patients. We suggest that this
      scattered picture has to do with the fourth line of research: lack of a good
      theory. Some of the extant theoretical models are reviewed, including placebo,
      water structure, silica contamination, energy models, and entanglement models. It
      emerges that local models, suggesting some change in structure in the solvent,
      are far from convincing. The nonlocal models proposed would predict that it is
      impossible to nail down homeopathic effects with direct experimental testing and
      this places homeopathy in a scientific dilemma. We close with some suggestions
      for potentially fruitful research.

PMID- 16296916
TI  - Are randomized controlled trials (RCTs) redundant for testing the efficacy of
      homeopathy? A critique of RCT methodology based on entanglement theory.
AB  - INTRODUCTION: Randomized controlled trials (RCTs) have yet to deliver unequivocal
      results demonstrating the efficacy (or otherwise) of homeopathic remedies and
      individualized homeopathic prescribing. This could be caused by an implicit
      assumption inherent in RCT methodology that specific effects of a remedy and any
      nonspecific effects of consultation are independent of each other. Reported here
      is a theoretical investigation of the consequences arising from this assumption
      proving to be false. METHODS: A previously developed theoretical model of
      entanglement in homeopathy between patient, practitioner, and remedy (called PPR
      entanglement) was used in this investigation. RESULTS: The adherence to RCT
      methodology could result in such trials completely disrupting the formation or
      survival of any three-way PPR entangled state. CONCLUSIONS: Assuming the PPR
      entangled state is a necessary condition for therapeutic interaction,
      alternatives to RCTs are urgently required that can take into account possible
      entangled specific and nonspecific effects during trials of homeopathy. That RCTs
      sometimes deliver positive results for the use of homeopathic remedies may be
      caused by residual entanglement arising from homeopathic remedy manufacture.

PMID- 16296917
TI  - Efficacy of the potentized homeopathic drug, Carcinosin 200, fed alone and in
      combination with another drug, Chelidonium 200, in amelioration of p
      dimethylaminoazobenzene-induced hepatocarcinogenesis in mice.
AB  - OBJECTIVES: This study was conducted to examine whether the potentized
      homeopathic remedy Carcinosin 200, fed alone and in combination with Chelidonium
      200, has differential protective effects against p-dimethylaminoazobenzene (p
      DAB)-induced hepatocarcinogenesis in mice. DESIGN: Liver tumors were induced in
      mice through chronic feeding of p-DAB (initiator) and phenobarbital (PB,
      promoter). The mice were divided into two subgroups: (1) one was fed potentized
      Alcohol 200 and served as controls; and (2) the other was fed Carcinosin 200
      alone or in combination with Chelidonium 200 and divided into several sets. The
      relative efficacy of the two potentized remedies, alone or in combination, in
      combating hepatocarcinogenesis was assessed through several cytogenetical
      endpoints such as chromosome aberrations, induction of micronuclei, sperm head
      anomaly, and mitotic index at several intervals of fixation (days 7, 15, 30, 60,
      90, and 120). Several toxicity biomarkers such as acid and alkaline phosphatases,
      glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and lipid
      peroxidation activity were also assayed in three organs of treated and control
      mice. In addition, recovery by the homeopathic drugs, if any, of tissue damage
      inflicted because of chronic feeding of p-DAB and PB was also assessed by
      optical, scanning, and transmission electron microscopies of liver done at days
      60 and 120. RESULTS: Both Carcinosin 200 and Chelidonium 200 when administered
      alone show considerable ameliorative effect against p-DAB-induced
      hepatocarcinogenesis in mice; but the conjoint feeding of these two drugs appears
      to have had a slightly greater protective effect. CONCLUSIONS: These homeopathic
      remedies have the potential to be used as complementary and alternative medicine
      in liver cancer therapy, particularly as supporting palliative measures.

PMID- 16296918
TI  - Antiviral activity of Engystol: an in vitro analysis.
AB  - OBJECTIVES: To study the effects of the homeopathic preparation Engystol
      (Biologische Heilmittel HEEL GmbH, Baden-Baden, Germany) on a panel [corrected]
      of human pathogenic viruses in vitro. DESIGN: The effects of Engystol were
      studied using plaque-reduction assays and virus titration assays, and by
      quantification of newly synthesized viral proteins in virus-specific enzyme
      linked immunoabsorbent assays (ELISAs). SUBJECTS: The DNA viruses Adeno 5 and
      herpes simplex type 1 (HSV-1), the RNA virus respiratory syncytial virus (RSV),
      and human rhinovirus (HRV). RESULTS: A 73% reduction of Adeno 5 specific proteins
      and an 80% reduction in HSV-1 specific proteins were observed in ELISAs of virus
      infected cells treated with Engystol after infection. The effects appeared to be
      dose-dependent. With these viruses, similar results were observed in titration
      assays of viral offspring from cells treated with Engystol. Pretreatment of
      adenovirus with Engystol did not inhibit the infectivity of the virus suspension
      and no Engystol-induced stimulation of interferon-alpha could be observed. Plaque
      reduction assays with the RNA viruses, RSV and HRV, showed reductions in
      infectivity by 37% (RSV) and 20% (HRV), respectively. CONCLUSIONS: The results
      indicate antiviral activity of Engystol independent of the activation of the
      cellular interferon system.

PMID- 16296921
TI  - Consumption of sweetened dried cranberries versus unsweetened raisins for
      inhibition of uropathogenic Escherichia coli adhesion in human urine: a pilot
      study.
AB  - OBJECTIVES: The aim of this study was to determine whether consumption of
      sweetened dried cranberries elicits urinary anti-adherence properties against
      Escherichia coli as previously demonstrated with cranberry juice and/or sweetened
      cranberry juice cocktail, compared to unsweetened raisins. DESIGN: Uropathogenic
      E. coli isolates were obtained from five women with culture-confirmed urinary
      tract infections (UTIs). Four urine samples were collected from each subject. The
      first urine sample was collected before any study intervention. The second urine
      sample was collected 2-5 hours after consumption of one box (42.5 g) of raisins.
      The third urine sample was collected 5-7 days later. The final urine sample was
      collected 2-5 hours after consumption of approximately 42.5 g of dried
      cranberries. MATERIALS AND METHODS: E. coli isolates were incubated separately in
      each of the four urine samples collected from the five subjects. Bacteria were
      harvested from the urine and tested for the ability to prevent adhesion of P
      fimbriated E. coli bacteria using a mannose-resistant hemagglutination assay with
      human red blood cells (A1, Rh+). RESULTS: Of the urine samples collected after
      dried cranberry consumption, one demonstrated 50% antiadherence activity, two
      demonstrated 25% activity, and two did not show any increased activity. None of
      the control urine samples and none of the postraisin consumption samples
      demonstrated any inhibitory activity. CONCLUSIONS: Data from this pilot study on
      only five subjects suggest that consumption of a single serving of sweetened
      dried cranberries may elicit bacterial antiadhesion activity in human urine,
      whereas consumption of a single serving of raisins does not. Further studies are
      needed to verify the antiadhesion effect of sweetened dried cranberries. In
      addition, dose-response and pharmacokinetics of the active compounds in the dried
      cranberries need to be determined. If clinical research is positive, dried
      cranberries could potentially be a viable alternative to cranberry juice
      consumption for prevention of UTIs.

PMID- 16296919
TI  - The effect of Gencydo injections on hayfever symptoms: a therapeutic causality
      report.
AB  - OBJECTIVES: The aim of this study was to study the effect of Gencydo (Weleda AG,
      Arlesheim, Switzerland) injections on hayfever symptoms. DESIGN: This is a
      therapeutic causality report based on the practices of 13 Dutch general
      practitioners. SUBJECTS: Thirteen (13) patients with a mean history of hayfever
      with grass pollen allergy of 9 years duration, who in previous years used
      conventional hayfever medication because of the severity of symptoms during the
      pollen season. INTERVENTIONS: Gencydo injections were given in 12 patients before
      the onset of and during the grass pollen season, and in one patient during the
      grass pollen season only. OUTCOME MEASURES: Nasal and non-nasal hayfever symptom
      severity, use of rescue medication (antihistamines or corticosteroids), and
      subjective experiences of patients were used as outcome measures. RESULTS: Nine
      (9) of 13 patients showed no increase of symptom severity during the so-called
      pollen season. Both the mean maximal total nasal symptom score per patient and
      the mean total nasal symptom score for the entire study group during the days
      with a grass pollen count >100 were mild. Percentages of individual "strong" or
      "severe" nasal symptom scores were low. There was no statistically significant
      difference in mean total nasal symptom score between the period when the pollen
      count was <100 and the period when it was >100. Conventional rescue medication
      for hayfever was used only eight times, all by one person. Nine (9) patients
      (69%) reported an improvement of symptoms (eight patients cited strong
      improvement and one patient noted slight improvement). CONCLUSIONS: There are
      clear indications that Gencydo treatment was effective in a large subgroup of the
      research population.

PMID- 16296922
TI  - Measurements of spontaneous ultraweak photon emission and delayed luminescence
      from human cancer tissues.
AB  - OBJECTIVE: The aim of this study was to measure spontaneous photon emission (SPE)
      and delayed luminescence (DL) from various human cancer tissues. MATERIALS AND
      METHODS: A photomultiplier tube attached to a dark chamber was used for the
      detection of ultraweak photon emission from cancer tissues in the chamber. The
      samples were illuminated with a 150 W metal halide lamp for the measurement of
      delayed luminescence. Frozen tissues were provided by the hospitals and preserved
      in saline solution in a CO2 incubator for 1 hour before starting the measurement
      of spontaneous photon emission. We successively measured the afterglows from the
      samples after 30-second irradiation of the lamp. The samples were divided into
      two groups: tumor tissues and normal tissues around tumor tissues. We presented
      experimental data and interpreted their characteristic patterns of spontaneous
      photon emission and delayed luminescence. RESULTS: Mean values of spontaneous
      photon emissions from the normal tissues and the tumor tissues were measured with
      the standard errors of the mean as 625 +/- 419 counts/minute/cm2 (n = 6) and 982
      +/- 513 counts/minute/cm2 (n = 14), respectively. Peak values of the intensity of
      delayed luminescence from normal and cancerous tissues were 63 +/- 20 counts/ms
      (n = 6) and 48 +/- 12 counts/ms (n = 14). CONCLUSIONS: The intensity of
      spontaneous photon emissions from cancer tissues were mostly discriminated from
      those of normal tissues, and their delayed luminescent properties were
      investigated.

PMID- 16296923
TI  - Bioelectrographic correlates of the direct vision phenomenon.
AB  - OBJECTIVES: A method for training children and adults to perceive visual
      information without using the eyes has been developed. A study was conducted to
      investigate the correlation of this perceptual capacity, known as direct vision
      (DV), with bioelectrographic measurements. DESIGN: Using the technique of dynamic
      digital gas-discharge visualization (GDV) bioelectrography, seven subjects were
      tested on three occasions over a 7-month period while they were in the process of
      reading information from a computer screen and reading printed text; this testing
      was repeated after an interval of 2 years. RESULTS: In multiple trials it was
      found that with the perception of information by DV, curves of GDV versus time
      exhibited specific dynamics, confirming the phenomenon of DV. At least three
      types of GDV characteristics can be distinguished in this state. This study also
      identified improvements in the psychosomatic state of children during the 7-month
      course of training in DV. CONCLUSIONS: The phenomenon of DV presents a newly
      recognized type of human information processing. It is based on a specific type
      of mental training that is statistically reproducible and has been assimilated by
      hundreds of children in Russia who are blind or have poor vision. The discovery
      of DV opens new perspectives in the study of the mechanisms of consciousness. The
      GDV characteristics that were observed during the perception of information by DV
      support the hypothesis that DV occurs through signals within the visible range of
      the electromagnetic spectrum. These results allow the proposal of a hypothesis
      for the way in which the brain, as well as the human system as a whole, registers
      information.

PMID- 16296924
TI  - Reduction of perception of chronic fatigue in an observational study of patients
      receiving 12 weeks of Kampo therapy.
AB  - OBJECTIVE: The aim of this study was to observe the influence of Kampo therapy on
      latent chronic fatigue of patients with chronic diseases. SUBJECTS: One hundred
      and seventy-three (173) consecutive patients with chronic diseases came to our
      department for the first time. DESIGN: This was a prospective study. Patients
      were divided into two groups: a chronic fatigue group (CFG) and a nonchronic
      fatigue group (NCFG). Based on Kampo diagnosis, both groups were prescribed Kampo
      formulae as an extract or decoction for 12 weeks. OUTCOME MEASURES: By using
      questionnaires, patients were assessed concerning their physical and mental types
      of fatigue, their sleep situation, and their attitude toward work or
      housekeeping, both before and after 12 weeks of treatment, according to Kampo
      diagnosis. RESULTS: The mental fatigue, physical fatigue, and sleep scores of
      both groups, and the work score of CFG, were decreased. The rate of reduction of
      the fatigue score was significantly greater in CFG than in NCFG. The factor
      responsible for this difference in fatigue score was physical fatigue.
      CONCLUSIONS: A reduction of the perception of chronic fatigue was observed in
      patients receiving 12 weeks of Kampo therapy.

PMID- 16296925
TI  - Differentiation of pheochromocytoma PC12 cells induced by human urine extract and
      the involvement of the extracellular signal-regulated kinase signaling pathway.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of a human urine
      preparation on the differentiation of tumor cells. DESIGN: The pheochromocytoma
      PC12 cells were used to examine the effects of a human urine preparation, CDA-2
      on the induction of differentiation markers, neurofilaments, and compared with
      that induced by nerve growth factor (NGF). The MAPK/ERK kinase (MEK) inhibitor
      U0126 was used to examine the involvement of mitogen-activated protein kinase
      (MAPK) signaling pathway in this differentiation inducing effect. RESULTS: We
      find that CDA-2 could induce differentiation of pheochromocytoma PC12 cells, as
      evidenced by the markedly increased expression of neurofilaments to a level
      comparable to those induced by NGF. This phenomenon was accompanied by the
      phosphorylation of extracellular-signal-regulated kinase (ERK) and could be
      inhibited by the MEK inhibitor, U0126. CONCLUSIONS: Our results demonstrate the
      presence of active components in the human urine extract that can induce
      differentiation of PC12 cells and may involve the ERK signaling pathway. This may
      provide new insights for seeking novel differentiation agents and offer hope for
      cancer patients.

PMID- 16296926
TI  - Dietary supplements and weight control in a middle-age population.
AB  - OBJECTIVES: Obesity is rapidly becoming a health problem of epidemic proportions,
      bringing with it a host of health concerns. This study investigates the
      association of long-term (10-year) use of 14 nutritional supplements, marketed as
      weight-control aids, with weight change over the past 10 years among individuals
      age 53 to 57 years. METHODS: Data are from the VITamins And Lifestyle (VITAL)
      cohort study of western Washington. Participants (n = 15,655) completed
      questionnaires about 10-year supplement use, diet, health habits, height, and
      present and former weights. The following supplements that are sometimes marketed
      for weight control or loss were examined: multivitamins; vitamins B6 and B12;
      chromium; coenzyme Q10, dehydroepiandrosterone, essential fatty acids (EFAs),
      fiber, garlic (Allium sativum), ginkgo (Ginkgo biloba), ginseng (Panax spp.),
      melatonin, soy, and St. John's wort (Hypericum perforatum). Linear regression was
      used to model 10-year change in weight from age 45 to ages 53-57, stratified by
      sex and body mass index (BMI, kg/m2) (normal, overweight, or obese) at age 45
      years. Models were controlled for race/ethnicity, education, energy intake,
      physical activity, weight at age 45 years, and smoking. RESULTS: Among overweight
      or obese men and women, long-term use of multivitamins, vitamins B6 and B12, and
      chromium were significantly associated with lower levels of weight gain. For
      example, with chromium, weight gain in the past 10 years for obese men was 11.7
      lb for no use, 6.1 lb for <150 microg/day (10-year average), and a weight loss of
      3.1 lb for > or = 150 microg/day (p for trend, <0.05). Among obese women, weight
      gain was 14.1 lb, 7.9 lb, and 3.2 lb for the three groups respectively (p for
      trend, <0.01). CONCLUSIONS: These data suggest that long-term users of certain
      supplements experienced less weight gain than individuals who did not use the
      supplements. Further study is necessary before recommendations regarding these
      supplements can be made.

PMID- 16296928
TI  - "Spooky actions at a distance": physics, psi, and distant healing.
AB  - Over decades, consciousness research has accumulated evidence of the real and
      measureable existence of "spooky actions at a distance"--modes of telepathy,
      telekinesis, clairvoyance, and the like. More recently scientists have begun
      rigorous study of the effects of distant healing intention and prayer vis-a-vis
      nonhuman living systems and patients in clinical trials. A barrier to taking such
      work seriously may be the belief that it is fundamentally incompatible with the
      scientific world view. This article suggests that it need not be; contemporary
      physics has generated a series of paradigms that can be used to make sense of,
      interpret, and explore "psi" and distant healing. Four such models are discussed,
      two drawn from relativity theory and two from quantum mechanics. First is the
      energetic transmission model, presuming the effects of conscious intention to be
      mediated by an as-yet unknown energy signal. Second is the model of path
      facilitation. As gravity, according to general relativity, "warps" space-time,
      easing certain pathways of movement, so may acts of consciousness have warping
      and facilitating effects on the fabric of the surrounding world. Third is the
      model of nonlocal entanglement drawn from quantum mechanics. Perhaps people, like
      particles, can become entangled so they behave as one system with instantaneous
      and unmediated correlations across a distance. Last discussed is a model
      involving actualization of potentials. The act of measurement in quantum
      mechanics collapses a probabilistic wave function into a single outcome. Perhaps
      conscious healing intention can act similarly, helping to actualize one of a
      series of possibilities; for example, recovery from a potentially lethal tumor.
      Such physics-based models are not presented as explanatory but rather as
      suggestive. Disjunctions as well as compatibilities between the phenomena of
      modern physics and those of psi and distant healing are explored.

PMID- 16296927
TI  - Patterns of use of nonbiomedical medicine services by nonbiomedical medicine
      providers.
AB  - OBJECTIVES: The aim of this study was to characterize the patterns of use of
      nonbiomedical medicine compared to biomedical medicine among providers of
      nonbiomedical medicine in order to assess the degree of confidence the providers
      have in nonbiomedical medicine. MATERIALS AND METHODS: Anonymous, self
      administered questionnaires were distributed among the providers of care in
      nonbiomedical medicine clinics in Israel. RESULTS: Ninety-two (92) of 127
      questionnaires were completed (73% response rate). Fifty-four percent (54%) were
      women and 76% were Israeli-born. Nineteen percent (19%) had M.D. degrees and 83%
      received training in nonbiomedical medicine in Israel. In the course of the 12
      months preceding the survey, 62% of the providers were treated by nonbiomedical
      medicine techniques; of these, 54% chose these techniques as their first
      treatment of choice. The vast majority (97%) expressed satisfaction with the
      results of this treatment. Fifty-five percent (55%) stated that they would turn
      to both nonbiomedical and biomedical medicine in the future for acute medical
      problems; 28% declared that they would turn first to nonbiomedical medicine,
      compared to 14%, who said they would turn first to biomedical medicine. A similar
      result was seen for chronic medical problems. More than two thirds of those who
      turned to nonbiomedical medicine treatment asked for acupuncture. Eighty-seven
      percent (87%) of acupuncture providers also preferred this mode of treatment.
      CONCLUSIONS: Providers of nonbiomedical medicine care prefer to combine
      nonbiomedical and biomedical medicine treatment for their own acute and chronic
      medical problems. The preferred method of therapy was acupuncture. These patterns
      of use demonstrate that providers have confidence in these methods of treatment
      alongside biomedical medicine.

PMID- 16296929
TI  - Exploring the role of complementary and alternative medicine in public health
      practice and training.
AB  - OBJECTIVES: Consumer use of complementary and alternative medicine (CAM) in the
      United States continues to expand. Although conventional medicine has responded
      actively, the response from public health has been far less pronounced. To
      examine the potential for integrating CAM into public health contexts, an
      exploratory survey was conducted. DESIGN: A 19-item, self-administered survey
      instrument was used to collect participant data. SETTINGS/LOCATION: Participants
      were surveyed at the 2003 American Public Health Association (APHA) annual
      meeting while attending CAM-related talks sponsored by the Alternative and
      Complementary Health Practices Special Interest Group (ACHP SPIG). SUBJECTS: A
      convenience sample of 153 individuals was surveyed, which was predominantly
      female (81%) and Caucasian (68%), with an average age of 42 years. OUTCOME
      MEASURES: The survey instrument included items about participant and client
      demographics, participant use of CAM (personal and professional), perceived
      client interest in CAM, and several attitude measures. RESULTS: The majority of
      participants (64%) were currently employed as public health professionals working
      in a wide variety of settings with highly diverse populations. Personal use of
      CAM was high (66% using four or more modalities). The majority also reported
      integrating CAM into work settings. There was a significant relationship between
      personal and professional use of CAM. Participants overwhelmingly agreed that
      more professional training in this area was needed. CONCLUSIONS: This exploratory
      study provides insight into the potential role of CAM as an important resource in
      public health settings. Additional funding and research in this area is urgently
      needed.

PMID- 16296941
TI  - Pharmacogenetics--where are we and where are we heading?

PMID- 16296930
TI  - The spectrum of therapeutic influences and integrative health care: classifying
      health care practices by mode of therapeutic action.
AB  - The growing popularity of complementary and alternative medicine (CAM) and
      integrative medicine (IM) highlight the need for a clinically relevant system for
      classifying health care practices. All systems, modalities, and techniques of
      health care (conventional, complementary, alternative, and traditional) can be
      organized in categories of "primary mode of therapeutic action." This results in
      six categories: biochemical; biomechanical; mind-body; energy; psychological
      (symbolic); and nonlocal. In each category, there are subdivisions. Organizing
      health care by primary mode of therapeutic action has numerous benefits: (1)
      conventional and CAM practitioners, and the public, can readily see some of the
      general similarities and differences among practices; (2) health care educators
      gain a common foundation and shared language for explaining CAM and IM; (3)
      professionals and the public, wishing to combine dissimilar practices, gain a
      common framework for evaluating the meaning of integration; and (4) the crossover
      problem can be understood as a natural occurrence in health care, not a confusing
      intellectual dilemma. The National Center for Complementary and Alternative
      Medicine (NCCAM) system of categories for CAM is briefly critiqued.

PMID- 16296943
TI  - Pharmacogenomics and Clinical R&D.

PMID- 16296944
TI  - Flavin-containing monooxygenase genetic polymorphism: impact on chemical
      metabolism and drug development.
AB  - The flavin-containing monooxygenases (FMOs) metabolize a broad range of
      therapeutics. Consisting of five gene products in humans (FMO1-5), the different
      FMO family members exhibit pronounced tissue- and temporal-specific expression
      patterns. Substantial interindividual differences are also observed, and the
      inability to modulate with exogenous agents is consistent with an important role
      for genetic variation. Several rare FMO3 alleles causative for trimethylaminuria
      have been well characterized. However, the identification and characterization of
      functional FMO1-5 polymorphisms has been more recent. Although none of these
      polymorphisms has been associated with an adverse drug reaction, the continued
      broadening of our therapeutic armamentarium makes such an event likely in the
      future. Furthermore, at least one example has been reported for a direct
      association between FMO3 polymorphism and therapeutic efficacy. Thus, it is
      anticipated that knowledge regarding functionally-relevant FMO genetic
      variability will become increasingly important for making drug development and
      patient therapeutic choices.

PMID- 16296945
TI  - Multifactor dimensionality reduction for detecting gene-gene and gene-environment
      interactions in pharmacogenomics studies.
AB  - In the quest for discovering disease susceptibility genes, the reality of gene
      gene and gene-environment interactions creates difficult challenges for many
      current statistical approaches. In an attempt to overcome limitations with
      current disease gene detection methods, the multifactor dimensionality reduction
      (MDR) approach was previously developed. In brief, MDR is a method that reduces
      the dimensionality of multilocus information to identify polymorphisms associated
      with an increased risk of disease. This approach takes multilocus genotypes and
      develops a model for defining disease risk by pooling high-risk genotype
      combinations into one group and low-risk combinations into another. Cross
      validation and permutation testing are used to identify optimal models. While
      this approach was initially developed for studies of complex disease, it is also
      directly applicable to pharmacogenomic studies where the outcome variable is drug
      treatment response/nonresponse or toxicity/no toxicity. MDR is a nonparametric
      and model-free approach that has been shown to have reasonable power to detect
      epistasis in both theoretical and empirical studies. This computational
      technology is described in detail in this review, and its application in
      pharmacogenomic studies is demonstrated.

PMID- 16296946
TI  - Advances and challenges in fluoropyrimidine pharmacogenomics and
      pharmacogenetics.
AB  - In cancer pharmacogenetics (the study of how variability in a single or set of
      known genes influences drug response) and pharmacogenomics (the study of
      variability on a genome-wide scale), one of the most important fields of research
      focuses on the fluoropyrimdines (FPs) and, in particular, 5-fluorouracil (5-FU).
      After over 40 years of use, FPs remain one of the most commonly used cancer
      chemotherapy agents and their application includes a wide spectrum of cancer
      types. FPs also continue to be the baseline component for many new regimens with
      novel molecular-targeted agents that are being rapidly introduced. Hence, it
      would seem appropriate that pharmacogenetic/genomic models for optimizing cancer
      patient management would involve indicators of FP response. In this article, the
      current trends in FP pharmacogenetics and pharmacogenomics are reviewed based on
      the advances made to date and the challenges faced in realizing their full
      potential.

PMID- 16296947
TI  - Pharmacogenetics and anesthesiologists.
AB  - Genetic variation contributes to an individual's sensitivity and response to a
      variety of drugs important to anesthetic practice. Early insights into the
      clinical impact of pharmacogenetics were provided by anesthesiology-
      investigations into prolonged apnea after succinylcholine administration,
      thiopental-induced porphyria and malignant hyperthermia contributed to the novel
      science of pharmacogenetics in the early 1960s. Genetic polymorphisms involved in
      pharmacokinetics (absorption, distribution, metabolism, and excretion of drugs)
      and pharmacodynamics (receptors, ion channels and enzymes) can affect an
      individual's response to the drugs used in anesthetic practice. In addition,
      genetic variation in proteins directly unrelated to drug action or metabolism can
      influence responses to environmental changes that occur during anesthesia. This
      review will summarize the current knowledge of genetic variation in response to
      drugs relevant to anesthesia, and how this impacts upon clinical practice.

PMID- 16296948
TI  - Pharmacogenomics and drug development.
AB  - It is generally anticipated that pharmacogenomic information will have a large
      impact on drug development and will facilitate individualized drug treatment.
      However, there has been relatively little quantitative modeling to assess how
      pharmacogenomic information could be best utilized in clinical practice. Using a
      quantitative model, this review demonstrates that efficacy is increased and
      toxicity is reduced when a genetically-guided dose adjustment strategy is
      utilized in a clinical trial. However, there is limited information available
      regarding the genetic variables affecting the disposition or mechanism of action
      of most commonly used medications. These genetic factors must be identified to
      enable pharmacogenomic testing to be routinely used in the clinic. A recently
      described murine haplotype-based computational genetic analysis method provides
      one strategy for identifying genetic factors regulating the pharmacokinetics and
      pharmacodynamics of commonly used medications.

PMID- 16296949
TI  - Physiogenomic analysis links serum creatine kinase activities during statin
      therapy to vascular smooth muscle homeostasis.
AB  - Statins are highly effective at reducing coronary disease risk. The main side
      effects of these medications are a variety of skeletal muscle complaints ranging
      from mild myalgia to frank rhabdomyolysis. To search for physiologic factors
      possibly influencing statin muscle toxicity, we screened for genetic associations
      with serum creatine kinase (CK) levels in 102 patients receiving statin therapy
      for hypercholesteremia. A total of 19 single nucleotide polymorphism (SNPs) were
      selected from ten candidate genes involved in vascular homeostasis. Multiple
      linear regression was used to rank the SNPs according to probability of
      association, and the most significant associations were analyzed in greater
      detail. SNPs in the angiotensin II Type 1 receptor (AGTR1) and nitric oxide
      synthase 3 (NOS3) genes were significantly associated with CK activity. These
      results demonstrate a strong association between CK activity during statin
      treatment and variability in genes related to vascular function, and suggest that
      vascular smooth muscle function may contribute to the muscle side effects of
      statins.

PMID- 16296950
TI  - Concordance of pharmacogenetic markers in germline and colorectal tumor DNA.
AB  - INTRODUCTION: Most cancer pharmacogenetic studies use germline DNA, as tumor
      tissue is often inaccessible in the advanced disease setting. However, this
      relies on the assumption that germline DNA is representative of the tumor
      genotype. To date, there has been little attention paid to defining the
      relationship between tumor and germline genomes. MATERIALS AND METHODS: This
      study compared 28 polymorphisms in 13 genes of high importance to cancer
      pharmacogenetics from ten different chromosome regions, in DNA from normal mucosa
      and colon tumors in 44 paired samples. RESULTS: 93% of samples had one or fewer
      genotype discrepancies. 77% of patients had intraindividual genotypes in complete
      concordance. In addition, although microsatellite instability (MSI) was
      identified in 20% of tumors, no significant association between MSI and genotype
      discrepancies was observed (p = 0.672). CONCLUSIONS: While this data validates
      the use of germline DNA pharmacogenetics in colorectal cancer, statistical
      analysis and modeling of pharmacogenetic data should be employed to incorporate
      this small, but important, source of error.

PMID- 16296951
TI  - Translating RNA interference into therapies for human disease.
AB  - RNA interference (RNAi) represents one of the most promising new frontiers in
      drug discovery. Breakthroughs in understanding RNA's extensive natural role in
      essential cellular processes have opened up the potential for a whole new class
      of drugs based on RNAi. Harnessing the natural process of RNAi, short, double
      stranded RNA molecules are able to inhibit expression of genes in a sequence
      specific manner. By targeting disease-causing genes, RNAi drugs have the
      potential to be more selective than traditional drugs, and thus more effective as
      well as less toxic. Over the past few years, important strides have been made in
      translating the promise of RNAi into therapies for human disease. In contrast to
      the extensive lead optimization steps typically required in small-molecule and
      protein drug discovery, RNAi drug candidates can be identified using
      bioinformatics to select sequences complementary to the target mRNA. The process
      of selecting an RNAi-based drug candidate may simply involve the synthesis and
      testing of a relatively small number of short double strands (duplexes) of RNA,
      incorporating chemical modifications that confer stability and direct these RNA
      duplexes to the appropriate tissues and cells, and/or formulating these RNA
      duplexes with appropriate delivery agents to achieve the same goals. As advances
      in RNAi therapeutics continue, the decades to come should bring a potent new
      class of drugs based on RNAi.

PMID- 16296952
TI  - Questioning the sustainability of primary health care innovation.

PMID- 16296954
TI  - Caring for a marginalised community: the costs of engaging with culture and
      complexity.
AB  - The Care and Prevention Programme (CPP) began in 1998. It is based on the
      philosophy of primary health care, and has improved health among homosexually
      active men, including about a third of HIV-positive South Australians. The CPP
      was assessed using financial analysis and qualitative methods. Participants
      wanted to access care where they could feel comfortable and safe to talk about
      issues of sexuality and lifestyle. The CPP model is "economically" sustainable,
      but not "financially" sustainable within the Medicare Benefits Schedule. It is
      vulnerable to changes in political environment. The financing model for the CPP
      has been adapted by including state funding. General practitioners have adapted
      by lowering their personal incomes (but not quality of care). These adaptations
      have achieved fragile financial viability. Facilitators of sustainability for the
      CPP included: It is part of the community that it serves; The creation of deeply
      integrated networks of diversity-competent service providers; and "Virtuous non
      adaptability" of service providers in refusing to compromise care standards
      despite financial pressure to do so. Threats to sustainability included:
      Difficulty maintaining a diversity-competent workforce skilled in HIV medicine;
      Marginal financial viability; and Political vulnerability.

PMID- 16296953
TI  - Implementation of a SNAP intervention in two divisions of general practice: a
      feasibility study.
AB  - "SNAP" is a model for the general practice management of four common behavioural
      risk factors: smoking, nutrition, alcohol and physical activity. The SNAP program
      was developed for the Australian Government in 2002. In 2003 and 2004, a
      feasibility study was conducted in one urban and one rural division of general
      practice (DGP) in NSW, in partnership with their local area health services.
      Information technology support and referral directories were developed, based on
      an initial needs assessment, SNAP guidelines, a clinical summary chart, patient
      education materials, and general practitioner and staff training. GPs reported
      that the SNAP approach fitted general practice consultations well. After its
      implementation, they were more confident in using motivational interviewing and
      SNAP interventions and referred more frequently. The impact and sustainability of
      the SNAP program were limited by a lack of effective practice teamwork, poor
      linkages with referral services, and the lack of a business model to support SNAP
      in the practices. DGPs could play an important role in providing practice visits
      and resources to improve communication, education and collaboration to support
      SNAP programs.

PMID- 16296955
TI  - Sustainable chronic disease management in remote Australia.
AB  - The Sharing Health Care Initiative (SHCI) demonstration project, which aimed to
      improve management of chronic diseases, was implemented in four small remote
      communities in the Katherine region which are serviced by the Katherine West
      Health Board, a remote Aboriginal-community-controlled health organisation in the
      Northern Territory. We reviewed the project proposal, final report, evaluation
      reports and transitional funding proposal, and supplemented these with in-depth
      interviews with key individuals. We determined factors critical to the
      sustainability of the SHCI project in relation to context, community engagement,
      systems flexibility and adaptability, the availability and effect of information
      systems, and the human nature of health care and policy. The project had a
      significant impact on community awareness of chronic disease and an improvement
      in clinic processes. We found that a number of interrelated factors promoted
      sustainability, including: An implementation strategy sufficiently flexible to
      take account of local conditions; A high level of community engagement;
      Appropriate timeframes, timing and congruence between national policy and local
      readiness to implement a chronic disease project; Effective communication between
      participating organisations; Project champions (key individuals) in participating
      organisations; Effective use of monitoring and evaluation data; and Adequate and
      ongoing funding. The absence of a number of these factors, such as poor
      communication, inhibited sustainability. Other factors could both promote and
      inhibit. For example, the impact of key individuals was important, but could be
      idiosyncratic and have negative effects.

PMID- 16296956
TI  - Sustaining an Aboriginal mental health service partnership.
AB  - The Regional Aboriginal Integrated Social and Emotional (RAISE) Wellbeing program
      commenced in February 2003 as an Aboriginal mental health service partnership
      between one Aboriginal Health Service and three mainstream services: a community
      mental health team, a hospital mental health liaison, and an "outback" community
      counselling service. A case study method was used to describe the drivers
      (incentives for program development), linkage processes (structures and
      activities through which the partnership operated), and sustainability of the
      program. Program drivers were longstanding problems with Aboriginal peoples'
      access to mental health care, policy direction favouring shared service
      responsibility, and a relatively small amount of new funding for mental health
      that allowed the program to commence. Linkage processes were the important
      personal relationships between key individuals. Developing the program as a part
      of routine practice within and across the partner organisations is now needed
      through formal agreements, common care-management tools, and training. The
      program's sustainability will depend on this development occurring, as well as
      better collection and use of data to communicate the value of the program and
      support calls for adequate recurrent funds. The development of care-management
      tools, training and data systems will require a longer period of start-up funding
      as well as some external expertise.

PMID- 16296957
TI  - Exploratory economic analyses of two primary care mental health projects:
      implications for sustainability.
AB  - We evaluated an Internet-based psychological intervention supported by either
      general practitioners or psychologists (Panic Online), and a Primary-care
      Evidence-based Psychological-interventions (PEP) strategy which involves training
      GPs to deliver specific psychological interventions. Economic modelling suggests
      that Panic Online is cost-effective when supported by either GPs or
      psychologists. Threshold analysis of the psychological training of GPs suggests
      that a modest effect size for clinical benefit would be sufficient to provide an
      acceptable cost-effectiveness ratio. The sustainability of these approaches
      depends on a range of factors, including funding, workforce availability, and
      acceptability to consumers and health care providers.

PMID- 16296958
TI  - Emergent themes in the sustainability of primary health care innovation.
AB  - A synthesis of the findings of the five studies of sustainability of primary
      health care innovation across six domains (political, institutional, financial,
      economic, client and workforce) yielded three main themes. These were: the
      importance of social relationships, networks and champions; the effect of
      political, financial and societal forces; and the motivation and capacity of
      agents within the system. The need for routine assessment of the sustainability
      of primary health care innovations is discussed. Given the dearth of literature
      on the sustainability of primary health care innovation, there is potential to
      develop a program of research directed towards a future synthesis of evidence.

PMID- 16296959
TI  - Surgical accountability: a framework for trust and change.

PMID- 16296960
TI  - Screening couples for cystic fibrosis carrier status: why are we waiting?

PMID- 16296961
TI  - A national sexually transmissible infections strategy: the need for an all
      embracing approach.

PMID- 16296962
TI  - The Western Australian Audit of Surgical Mortality: advancing surgical
      accountability.
AB  - OBJECTIVE: To describe the peer review process of the Western Australian Audit of
      Surgical Mortality (WAASM), selected outcomes and recommendations. STUDY DESIGN:
      Prospective audit using peer review of all cases of patients who died while under
      the care of a Western Australian surgeon between 1 January 2002 and 30 June 2004.
      Audit reviews were current to 30 September 2004. PARTICIPANTS AND SETTING: 194 of
      202 surgeons participated after a patient died under their care. MAIN OUTCOME
      MEASURES: Surgeon participation, deficiencies of care, deep vein thrombosis (DVT)
      prophylaxis, futile surgery, postmortem reviews, proportion of operations
      performed by consultant surgeons. RESULTS: The audit process was complete for 896
      of 1647 reported deaths (54%), while a further 503 (31%) were still under review
      at 30 September 2004. Twenty deaths associated with terminal care were excluded
      from analysis. Median patient age was 80 years, and 799 of the 876 patients who
      died (91%) had significant comorbidities that increased the risk of death.
      Deficiencies of care were reported in 179/876 (20%). In 45/876 deaths (5%) the
      deficiency of care was assessed to have caused the death, and 15 deaths were
      considered preventable. The risk of a deficiency of care was 1.9 times higher in
      elective admissions than emergency admissions. Autopsy was undertaken in 83/768
      (11%) deaths with complete data. Changes in practice were noted in some areas
      targeted by WAASM, such as improved DVT prophylaxis. A problem with fluid
      management was recorded. CONCLUSION: Most patients who died were elderly, had
      complex comorbidities and were treated appropriately. The WAASM has helped to
      change surgical practice and emphasises the importance of ongoing systematic
      audit. The participation of surgeons demonstrates their commitment to
      accountability and supports the intention of the Royal Australasian College of
      Surgeons to extend the process throughout Australia and New Zealand.

PMID- 16296963
TI  - Efficacy of an alcohol/chlorhexidine hand hygiene program in a hospital with high
      rates of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection.
AB  - OBJECTIVE: To assess the effect of a multifaceted hand hygiene culture-change
      program on health care worker behaviour, and to reduce the burden of nosocomial
      methicillin-resistant Staphylococcus aureus (MRSA) infections. DESIGN AND
      SETTING: Timetabled introduction of interventions (alcohol/chlorhexidine hand
      hygiene solution [ACHRS], improved cleaning of shared ward equipment, targeted
      patient decolonisation, comprehensive "culture change" package) to five clinical
      areas of a large university teaching hospital that had high levels of MRSA. MAIN
      OUTCOME MEASURES: Health care worker hand hygiene compliance; volume of ACHRS
      used; prevalence of patient and health care worker MRSA colonisation;
      environmental MRSA contamination; rates of clinical MRSA infection; and rates of
      laboratory detection of ESBL-producing Escherichia coli and Klebsiella spp.
      RESULTS: In study wards, health care worker hand hygiene compliance improved from
      a pre-intervention mean of 21% (95% CI, 20.3%-22.9%) to 42% (95% CI, 40.2%-43.8%)
      12 months post-intervention (P < 0.001). ACHRS use increased from 5.7 to 28.6
      L/1000 bed-days. No change was observed in patient MRSA colonisation or
      environmental colonisation/contamination, and, except in the intensive care unit,
      colonisation of health care workers was unchanged. Thirty-six months post
      intervention, there had been significant reductions in hospital-wide rates of
      total clinical MRSA isolates (40% reduction; P < 0.001), patient-episodes of MRSA
      bacteraemia (57% reduction; P = 0.01), and clinical isolates of ESBL-producing E.
      coli and Klebsiella spp (90% reduction; P < 0.001). CONCLUSIONS: Introduction of
      ACHRS and a detailed culture-change program was effective in improving hand
      hygiene compliance and reducing nosocomial MRSA infections, despite high-level
      MRSA endemicity.

PMID- 16296964
TI  - Risk of complications in a second pregnancy following caesarean section in the
      first pregnancy: a population-based study.
AB  - OBJECTIVE: To estimate the risks of maternal and perinatal morbidity and
      mortality in a second pregnancy, attributable to caesarean section in a first
      pregnancy. DESIGN AND SETTING: Cross-sectional analytic study of hospital births
      in New South Wales, based on linked population databases. PARTICIPANTS: 136 101
      women with one previous birth who gave birth to a singleton infant in NSW in 1998
      2002. MAIN OUTCOME MEASURES: Crude and adjusted odds ratios (aOR) and 95%
      confidence intervals (95% CI) for maternal and perinatal morbidity and mortality.
      RESULTS: 19% of mothers had a caesarean section in their first pregnancy.
      Compared with mothers who had had primary vaginal births, mothers who had had
      primary caesarean section and underwent labour in the second birth were at
      increased risk of uterine rupture (aOR, 12.3; 95% CI, 5.0-30.1; P < 0.0001),
      hysterectomy (3.5; 1.5-8.4; P < 0.01), postpartum haemorrhage (PPH) following
      vaginal delivery (1.6; 1.4-1.7; P < 0.0001), manual removal of placenta (1.3; 1.1
      1.6; P < 0.01), infection (6.2; 4.7-8.2; P < 0.0001) and intensive care unit
      (ICU) admission (3.1; 2.1-4.7; P < 0.0001); among mothers who did not undergo
      labour (ie, had an elective caesarean section), there was a lower risk of PPH
      (0.6; 0.5-0.7; P < 0.0001) and ICU admission (0.4; 0.3-0.5; P < 0.0001). For
      infants there was increased risk of preterm delivery (1.2; 1.1-1.3; P < 0.0001)
      and neonatal intensive care unit admission following labour (1.6; 1.4-1.9; P <
      0.0001) in the birth after primary caesarean section. The occurrence of
      stillbirth was not modified by labour. CONCLUSIONS: Caesarean section in a first
      pregnancy confers additional risks on the second pregnancy, primarily associated
      with labour. These should be considered at the time caesarean section in the
      first pregnancy is being considered, particularly for elective caesarean section
      for non-medical reasons.

PMID- 16296965
TI  - Empiric management of community-acquired pneumonia in Australian emergency
      departments.
AB  - OBJECTIVE: To describe empiric community-acquired pneumonia (CAP) management in
      Australian hospital emergency departments (EDs) and evaluate this against
      national guidelines, including use of the pneumonia severity index and antibiotic
      selection. DESIGN: A multicentre, cross-sectional, retrospective audit, April
      2003 to February 2005. SETTING: 37 Australian hospitals: 22 principal referral
      hospitals, six large major city hospitals, four large regional hospitals, four
      medium hospitals and one private hospital. PARTICIPANTS: Adult patients with a
      diagnosis of CAP made in the ED. Data on 20 consecutive CAP ED presentations were
      collected in participating hospitals. OUTCOME MEASURES: Documented use of the
      pneumonia severity index, initial antibiotic therapy prescribed in the ED,
      average length of stay, inpatient mortality, and concordance with national
      guidelines. RESULTS: 691 CAP presentations were included. Pneumonia severity
      index use was documented in 5% of cases. Antibiotic therapy covering common
      bacterial causes of CAP was prescribed in 67% of presentations, although overall
      concordance with national guidelines was 18%. Antibiotic prescribing was
      discordant due to inadequate empiric antimicrobial cover, allergy status
      (including contraindication to penicillin), inappropriate route of administration
      and/or inappropriate antibiotic choice according to recommendations. There was no
      significant difference between concordant and discordant antibiotic prescribing
      episodes in average length of stay (5.0 v 5.7 days; P = 0.22) or inpatient
      mortality (1.6% v 4.1%; chi2 = 1.82; P = 0.18). CONCLUSIONS: Antibiotic therapy
      for CAP prescribed in Australian EDs varied. Concordance with national CAP
      guidelines was generally low. Targeted interventions are required to improve
      concordance.

PMID- 16296966
TI  - Management of unprotected sexual encounters.
AB  - After "unprotected" sexual encounters, sexual history guides risk assessment and
      testing for sexually transmissible infections (STIs). Chlamydia trachomatis
      infection is the most prevalent bacterial STI. Sexually active young people (aged
      < 25 years) should have annual chlamydia testing. Opportunistic STI testing is
      indicated for population groups at increased risk of STI, including young people,
      gay and other homosexually active men, and Indigenous people. Gay and other
      homosexually active men should be regularly tested for HIV, syphilis, chlamydia
      and gonorrhoea. Indigenous people should be regularly tested for syphilis,
      chlamydia and gonorrhoea. Postexposure antiretroviral prophylaxis may be
      indicated after high-risk sexual encounters.

PMID- 16296967
TI  - Health care safety: what needs to be done?
AB  - Recent MJA editorials assert that Australian hospitals are no safer than they
      were when the first hospital safety report was published in 1995. Despite many
      recommendations by several committees and much activity to improve safety over
      the past decade, we lack concrete evidence that safety and quality of health care
      have improved. Efforts to promote hospital safety in the United States and the
      United Kingdom also remain unevaluated. Incentives for safer care have been
      implemented locally, but not applied to entire health systems. A recent review in
      Australia has recommended replacing the current Australian Council for Safety and
      Quality in Health Care with a smaller Commission on Safety and Quality in Health
      Care. The Commission will link all national safety activity and report annually
      to Australian health ministers on hospital safety. We need a system that measures
      quality and safety, and provides financial incentives for safer care.
      Implementing the national framework for education about patient safety would
      develop teamwork skills and skills in techniques of continuous improvement.
      Linked to this, adequate financial support should be available to make safety
      changes in the health care environment.

PMID- 16296968
TI  - Erythema induratum: a case of mistaken identity.

PMID- 16296969
TI  - A potentially fatal prescribing error in the treatment of paracetamol poisoning.

PMID- 16296970
TI  - Bezoar causing small bowel obstruction after repeated activated charcoal
      administration.

PMID- 16296971
TI  - 3. Is exercise good for you?
AB  - Physical activity can significantly reduce the risk of cardiovascular disease,
      diabetes, some forms of cancer, osteoporosis, obesity, falls and fractures, and
      some mental health problems. While the benefits of physical activity are clear,
      there is a slightly increased risk of sudden death while exercising (compared
      with while sedentary), especially in untrained people undertaking unaccustomed
      vigorous activity. Routine exercise testing yields a significant number of false
      positive results, and has not been shown to prevent exercise-related acute
      cardiac events. There is no convincing evidence that exercise is itself
      associated with osteoarthritis, but significant joint injury which occurs during
      sport is associated with an increased risk of subsequent development of
      osteoarthritis.

PMID- 16296972
TI  - Measurement, monitoring and clinical governance.

PMID- 16296973
TI  - Public reporting of individual surgeon performance.

PMID- 16296974
TI  - Dramatic changes for the better are already occurring.

PMID- 16296975
TI  - Optimising hospital systems comes first.

PMID- 16296976
TI  - A half-day each month for quality and safety activities.

PMID- 16296977
TI  - It's time to plan our future health system.

PMID- 16296978
TI  - 1928 Royal Commission "The fatalities at Bundaberg".

PMID- 16296979
TI  - Re-inventing the wheel?

PMID- 16296981
TI  - No barriers to chlamydia testing in sexually active young women.

PMID- 16296982
TI  - Community and health-care associated non-multiresistant methicillin-resistant
      Staphylococcus aureus in Victoria.

PMID- 16296983
TI  - Bisphosphonate-induced osteonecrosis of the jaw requires early detection and
      intervention.

PMID- 16296984
TI  - Spinal cord injury register for football: already tackled?

PMID- 16296985
TI  - Cancellation of operations on the day of intended surgery at a major Australian
      referral hospital.

PMID- 16296986
TI  - Detection of diagnostic and therapeutic radionuclides by US homeland security: a
      new travel hazard.

PMID- 16296987
TI  - Application of random amplified polymorphic DNA (RAPD) to detect the genotoxic
      effect of heavy metals.
AB  - This paper presents the results of a study on the influence of lead, copper,
      manganese and cadmium on DNA integrity in plant cells. Plants, as biological
      indicators, can measure the potential effects of pollutants when they are used to
      measure effects of heavy metals. The genotoxicity of heavy metals in kidney-bean
      (Phaseolus vulgaris) seedlings was subjected to RAPD (random amplified
      polymorphic DNA) analysis. An RAPD 'fingerprinting' technique was used to detect
      DNA damage in the kidney-bean seedlings treated with two selected heavy metals at
      concentrations of 150 and 350 mg x l(-1). Polymorphisms became evident as the
      presence and/or absence of DNA fragments in treated samples compared with the
      untreated one. At 350 mg x l(-1), a high number of both missing bands and new
      amplified fragment were observed. Results suggested that a qualitative measure
      reflecting changes in RAPD profiles were significantly affected at higher
      concentrations (350 mg x l(-1)) of the tested heavy metals. A total of 467 RAPD
      fragments in RAPD profiles were detected by using six random primers (decamers)
      and 224 of these fragments showed polymorphism. There was a distinct distance
      between the band patterns of treated plants and the control samples when the
      cluster method was applied. In addition, the result derived from numerical
      analysis revealed a considerable distance between the band pattern of the plant
      samples treated with 350 mg x l(-1) heavy metals and the control sample. Finally,
      a comparison between untreated and treated genomes shows that RAPD analysis can
      be used to evaluate how the environmental pollutants modify the structure of DNA
      in living organisms.

PMID- 16296989
TI  - Mental health nurse practitioners in Australia: improving access to quality
      mental health care.
AB  - Under The Nurses Amendment (Nurse Practitioners) Act 1998, New South Wales became
      the first state in Australia to legislate for nurse practitioners. Mental health
      was identified as a priority 'area of practice' for nurse practitioners. Issues
      surrounding the implementation of the nurse practitioner role in Australia and
      the potential for the role to address the current crisis in mental health nursing
      and the mental health sector will be discussed. The potential for partnerships
      with other health-care providers, in particular medical practitioners, will
      demonstrate how successful implementation of the role can fulfil consumer demand
      for primary prevention counselling, improve access to mental health services and
      early intervention, and provide mental health services that better reflect
      national priorities. This examination of the Australian context will be
      contrasted with a review of the overseas literature on mental health nurse
      practitioners.

PMID- 16296990
TI  - Retaining the mental health nursing workforce: early indicators of retention and
      attrition.
AB  - In the UK, strategies to improve retention of the mental health workforce feature
      prominently in health policy. This paper reports on a longitudinal national study
      into the careers of mental health nurses in the UK. The findings reveal little
      attrition during the first 6 months after qualification. Investigation of career
      experiences showed that the main sources of job satisfaction were caregiving
      opportunities and supportive working relationships. The main sources of
      dissatisfaction were pay in relation to responsibility, paperwork, continuing
      education opportunities, and career guidance. Participants were asked whether
      they predicted being in nursing in the future. Gender and ethnicity were related
      to likelihood to remain in nursing in 5 years time. Age, having children,
      educational background, ethnic background, and time in first job were associated
      with likelihood of remaining in nursing at 10 years. Associations between
      elements of job satisfaction (quality of clinical supervision, ratio of qualified
      to unqualified staff, support from immediate line manager, and paperwork) and
      anticipated retention are complex and there are likely to be interaction effects
      because of the complexity of the issues. Sustaining positive experiences,
      remedying sources of dissatisfaction, and supporting diplomats from all
      backgrounds should be central to the development of retention strategies.

PMID- 16296991
TI  - Promoting reflection in mental health nursing practice: a case illustration using
      problem-based learning.
AB  - Reflective practice in nursing has been shown to improve both client care and
      nurses role satisfaction. Students require regular and guided opportunities to
      learn the necessary reflective skills that underpin best practice. Problem-based
      learning (PBL) processes based on comprehensive learning packages developed from
      actual clinical cases provide a contextualized and realistic means for students
      to develop and hone their reflective skills for use as mental health
      practitioners. This paper uses a case illustration to demonstrate the usefulness
      of PBL as a mechanism for developing reflective practice in the mental health
      context. Students analysed five cases drawn from actual documented clinical
      materials that included nursing, medical and allied health professionals'
      assessments, treatment regimes, and progress notes. One student's written
      analysis of the five cases and an interview with the student is presented as a
      case illustration. The case illustrates the student's reflections on the theme of
      'hope' for the clients and identified three obstacles. These were: (i) a lack of
      acknowledgement by health professionals of traumatic life events; (ii)
      overlooking less tangible losses; and (iii) a central focus on drug treatment.
      Reflective learning strategies can be incorporated in on- and off-campus learning
      environments and used to assist the learner to practise critical reflective
      skills in a controlled and safe manner. Reflective processes are more meaningful
      if the PBL package that students encounter represents real clinical scenarios
      with comprehensive resource materials.

PMID- 16296992
TI  - The mixed attitudes of nurse's to caring for people with mental illness in a
      rural general hospital.
AB  - Mainstreaming of mental health care and the prevalence of mental illness have
      increased the requirement for care by nurses in the general hospital setting. In
      rural Australia, mental health services are limited and nurses have less access
      to support and education. Little is known about how these factors influence
      attitudes and the care of people with mental illness in rural hospitals. A
      qualitative descriptive study was used to investigate nurses' attitudes to caring
      for people with mental illness, the issues that impact on their ability to
      provide care, and the effect of education, experience, and support. In 2003, 10
      nurses from two wards in a rural hospital were interviewed. Participants from one
      ward had education and support from mental health nurses. Attitudes were found to
      be inextricably linked to issues that influence nurses' ability to provide care.
      Dislike was apparent from nurses who suggested it was not their role. Others
      identified fear, causing avoidance. Conversely, those receiving support and
      education described increased comfort, with some nurses expressing enthusiasm for
      mental health care, seeing it as integral to nursing. The priority of physical
      care, time constraints, environmental unsuitability, rurality, and the lack of
      skill, knowledge, and mental health services reduced safety and effective care. A
      limited ability to help was reported, despite support for Mental Health Strategy
      goals. Positive experience promoted through education and support was required
      for nurses to improve care and attitudes. Notably, collaboration with mental
      health nurses was identified as helping nurses overcome fear and increase
      competence in caring for people with mental illness.

PMID- 16296993
TI  - Sense of coherence and social support in relation to recovery in first-episode
      patients with major depression: a one-year prospective study.
AB  - Major depression is a common illness, with a lifetime prevalence rate of 10-13%
      for men and 21-24% for women. The experience of having a serious illness such as
      major depression affects the individual's quality of life and requires
      significant adaptation in order to cope. The aim of this study was to explore
      sense of coherence and social support in patients treated for a first episode of
      major depression in a 1-year follow up. The study design was prospective and
      longitudinal. A total of 24 patients, aged 18 years or over, with a first episode
      of major depression were included. Semi-structured interviews and self-assessment
      questionnaires were used at baseline as well as in a 1-year follow up in order to
      measure the level of severity of the depression, social support, and sense of
      coherence. The result showed that 71% of the patients had recovered at follow up.
      The sense of coherence scores were low at baseline, although the patients who
      recovered increased their sense of coherence scores significantly. Another factor
      of importance for recovery was a significant increase in social support. Social
      support is an important cornerstone in the restoration of a person's sense of
      coherence. It can be used in interventions that include the patient's family or
      close social network in combination with support to assist the patient to view
      his/her situation as comprehensible, manageable, and meaningful, thereby
      promoting or improving health. Mental health nurses are in a key position to
      identify patients' strengths and weaknesses so that the support and interventions
      provided can be tailored to meet the needs of each patient.

PMID- 16296994
TI  - A study of emotional attitude of psychiatric nurses: reliability and validity of
      the Nurse Attitude Scale.
AB  - In psychiatric nursing, the exchange of feelings among nurses and patients is
      vital. However, expressed emotion (EE) studies that have been performed in family
      studies of schizophrenia indicate that a high EE score can predict the relapse of
      schizophrenic patients. In the case of long-term inpatients at a psychiatric
      hospital in Japan, the emotional attitude of nurses towards patients is
      anticipated to have some effect on the course of the illness. In the present
      study, we revised part of the phrasing of the Japanese version of the Family
      Attitude Scale, and renamed it the Nurse Attitude Scale (NAS). We tested 189
      nurses with this scale, and examined reliability and validity. In a factor
      analysis of the NAS, three factors were extracted, which we termed criticism,
      hostility, and positive remarks. These factors are the same as items for
      assessment on the Camberwell Family Interview, a method of EE assessment.
      Cronbach's alpha for individual subscales was 0.848 for criticism, 0.845 for
      hostility, and 0.685 for positive remarks. With regard to test-retest
      reliability, there were significant correlations with values of 0.65 for
      criticism, 0.77 for hostility, and 0.44 for positive remarks. In addition, there
      was a significant correlation between the NAS and Pines' Burnout scores. These
      facts, thus suggested that the NAS represents an approximation of the EE of
      psychiatric nurses. In addition, these findings indicated that the state of
      burnout in psychiatric nurses resulted in a critical attitude towards patients.

PMID- 16296995
TI  - Community educators as supporters in ethnographic research.
AB  - The present article describes ethnographic research on the structure and function
      of bilingual community educators (CEs) as brokers of information involving
      culturally and linguistically diverse (CALD) communities. An important aspect of
      CE involvement was supporting the chief investigator to engage CALD communities
      to interpret their understanding of mental health and mental illness, and make
      appropriate choices about their health care. CEs advised the chief investigator
      on the appropriate use of language when dealing with mental and emotional health
      issues so that CALD community people were not isolated from the research process.
      The author contends that the benefit of CEs in ethnographic research is to help
      research teams synthesize different viewpoints to shape research questions and
      create workable solutions in local situations.

PMID- 16296996
TI  - Development of a mentorship programme for new graduate nurses in mental health.
AB  - A university and three area mental health services collaborated in developing a
      mentorship programme for new graduate nurses in mental health. The programme
      evolved from initiatives identified by the New South Wales Government to address
      recruitment and retention problems impacting on the mental health nursing
      workforce. This mentorship programme was identified as a strategy to potentially
      contribute to retention of novice nurses within the local mental health nursing
      workforce. New graduate nurses entering the mental health field were provided the
      opportunity to engage in a temporary supportive professional mentoring
      relationship. The present paper describes the background of the programme and
      provides an overview of how it was developed. It serves as a starting point for
      others contemplating developing similar programmes. Evaluation of the programme
      is incomplete, therefore, formal results will be presented in a subsequent paper.

PMID- 16296997
TI  - Patient or consumer? The colonization of the psychiatric clinic.
AB  - Information is given a privileged place in the psychiatric clinic, as illustrated
      by the prevalence and volume of data to be collected and forms to be completed by
      psychiatric nurses. Information though is different to knowledge. The present
      paper argues that information is part of a managerial discourse that implies
      commodification whereas knowledge is part of a clinical discourse that allows
      room for the suffering of the patient. Information belongs to the discourse of
      managerialism, one that positions the patient as customer/consumer and in doing
      so renders them unsuffering. The patient's suffering is silenced by their
      construction as a consumer. The discourse of managerialism seeks a complete data
      set of information. By way of contrast, another discourse, that of psychoanalysis
      offers the institution the idea that there are always holes, gaps, and
      uncertainty. The idea of uncertainty, gaps, things remaining unknown and a limit
      sits uncomfortably with the dominant discourse of managerialism; one that demands
      no limits, complete data sets, and many satisfied customers. This market model of
      managerialism denies the potential of the therapeutic relationship; that
      something curative might be produced via the transference. In addition, the
      managerialist discourse potentially positions the patient as both illegitimate
      and unsuffering.

PMID- 16296998
TI  - Some historical and epistemological remarks on itch and pruritus.
AB  - Although very common, itch is very hard to describe. It can be considered as one
      of the most distressing physical sensations we experience. Going back
      historically, old Latin and Greek writers cited it in ancient papers. So,
      etymology is of central importance to investigation in the field of itch,
      regarding the formation of a word with antique origins and different meanings.
      Scientists, poets, and painters for centuries tried to describe and represent
      itch. The study of their work reveals the development of the itch's significance.
      Today, a clinically relevant distinction defines pruritus and itch as two
      different sensations. Moreover, some terms like hyperknesis, alloknesis,
      atmoknesis, protopathic itch, and epicritic itch are described to approaching the
      complexity of this sensation and are utilized in clinical practice.

PMID- 16296999
TI  - Itch and pruritus: what are they, and how should itches be classified?
AB  - Itch and pruritus are two terms for the same thing. In this essay I will argue
      that casting about for a distinction between them creates only confusion. Once
      that matter is settled, it is still necessary to come up with a clinical
      classification for itches of different types. No system yet proposed, including
      the one that will be suggested here, is perfect.

PMID- 16297000
TI  - Neuroanatomy and neurophysiology of itch.
AB  - The specific pathway of "pure," histaminergic itch is traced from the mechano
      insensitive nerve fibers in the skin to their central cortical projections.
      Neuropathic itch created at different levels of this anatomical pathway is
      reviewed. In this review the present author discusses damage to pruritoceptors in
      the skin, entrapment syndromes, damage to spinal ganglia, nerve root impingement,
      injury of the spinal cord, and cerebral damage in the distribution of the middle
      cerebral artery, capsula interna, or thalamus. Itch in inflamed skin resulting
      from interactions between nerve transmitters and other mediators of inflammation
      is described.

PMID- 16297001
TI  - Itch and pain.
AB  - The discovery of a specialized neuronal pathway for itch has markedly improved
      our understanding of itch processing under physiological conditions. However, the
      complex interactions of pain and itch are only partly understood. This review
      focuses on the neurophysiological mechanisms involved in clinical and
      experimental itch conditions. There is emerging evidence that similar patterns of
      peripheral and central sensitization occur in chronic pain and chronic itch
      conditions. It will be of major interest to reveal whether the underlying
      mechanism for sensitization in the itch and pain pathways are also similar, as
      this might have major implications for therapy.

PMID- 16297002
TI  - Itch, pain, and metaesthetic sensation.
AB  - Itch is one of the alarm sensations that human beings have phylogenetically
      evolved for a defense purpose. Many theories and evidences regarding the
      biological, pathophysiological, and clinical aspects have been given, but an
      update on the neuroanatomy paths and consequent treatments is required. Some
      chemicals that are released after skin injury and facilitate the inflammatory
      process can induce itch or pain or basically lead to a sensitization of the
      nociceptor response. In clinical practice, the present authors note a continuum
      of sensations from touch to pain, among which many metaesthetic sensations can be
      described, even if the patients themselves cannot precisely define them. The
      specificity of itch neurons is therefore based on their spinal connections to the
      itch pathway rather than on unique peripheral receptors. The ambiguity of "itch
      unit" discharge to pruritics and algogens may be solved by the central inhibition
      of itch by pain: it is common knowledge that scratching relieves itching.
      Conversely, centrally acting pain-inhibiting opioids enhance itch by
      disinhibition. The relation between itch and pain is interesting in its clinical
      and physiopathological aspects in order to select appropriate treatment.

PMID- 16297003
TI  - Psyche, opioids, and itch: therapeutic consequences.
AB  - A patient's psychological condition can substantially affect the presence and
      severity of pruritus, a phenomenon thought to be mediated by the central nervous
      system's (CNS) opioid neurotransmitter system. Specific psychodermatologic
      disorders associated with psychogenic pruritus, including depression, anxiety,
      chronic tactile hallucinations, delusions of parasitosis, neurotic excoriations,
      and other cutaneous compulsions are likely controlled by this pathway. Therefore,
      in treating these conditions, medications specifically directed at the CNS can be
      the most effective therapies, whereas topical and supportive therapy may be
      important adjuncts in targeting the associated pruritus. Furthermore, the impact
      of an understanding clinician and a good physician-patient relationship cannot be
      underestimated in determining ultimate prognosis. This review will begin by
      discussing the relationship between the psyche and pruritus as well as the opioid
      neurotransmitter system. Following this, several disorders characterized by
      psychogenic pruritus will be described, and CNS-specific and adjunctive topical
      and supportive therapies for these conditions will be detailed.

PMID- 16297004
TI  - Itch in systemic disease: therapeutic options.
AB  - A new pathophysiologically based classification of itch is proposed, which should
      help the clinician adopt a rational approach to diagnosis and management of
      generalized itch. Focusing on neurogenic itch (itch without visible rash), common
      causes are reviewed and guidelines for laboratory and radiologic investigation
      are proposed. A stepwise approach to the management of generalized itch resulting
      from systemic disease is recommended. Specifically, the relative merits of broad
      versus narrowband ultraviolet B (UVB) are discussed and the pros and cons of
      doxepin, opioid antagonists, and selective serotonin reuptake inhibitors (SSRIs)
      such as paroxetine are considered. Attention is drawn to some novel approaches,
      including bright-light phototherapy and molecular adsorbent recirculating system
      (MARS) for selected patients with intractable itch caused by hepatic failure, and
      mirtazapine for nocturnal itch.

PMID- 16297005
TI  - Pharmacologic advances in the systemic treatment of itch.
AB  - Itch is propagated by complex mechanisms located both peripherally and within the
      central nervous system. For decades, novel treatments of itch have been slow to
      emerge, with the majority of focus on antagonism of histamine. Recently, with a
      new understanding of the pathophysiology of itch transmission, new treatment
      strategies have been elucidated. Opiate receptor antagonists, antidepressants,
      antiepileptics, and thalidomide are currently available therapeutic options that
      have benefited many patients with variegated sources of itch. In addition,
      research focused on the neuromediators of itch transmission has led to the
      development of novel targets for itch reduction and great potential for future
      therapies.

PMID- 16297006
TI  - Antihistamines and their role as antipruritics.
AB  - Antihistamines that bind to the histamine 1 receptor (H1) serve as important
      therapeutic agents to counter the effects of histamine in the skin. Two
      generations of antihistamines exist; however, second-generation agents are more
      advantageous because they cause less sedation, have a longer half life and are
      more selective for the H1 receptor. While H1 antihistamines have proven to be
      effective at reversing the pruritus and cutaneous lesions of chronic urticaria,
      their ability to treat pruritus associated with other cutaneous and systemic
      diseases is unproven.

PMID- 16297007
TI  - Topical anti-itch therapy.
AB  - Topical anti-itch therapy could be causative (antiviral, antimycotic, and/or
      antiparasitic preparations) or symptomatic. Symptomatic therapy includes
      substituting some other sensation by cooling, heating, and/or counterirritation,
      by anesthesia of sensory nerve endings with local anesthetics, blocking mediators
      of pruritus (to deplete substance P or to block acetylcholine release), and
      reducing inflammation of the skin with corticosteroids or topical
      immunomodulators (pimecrolimus and tacrolimus). In addition to drugs, the patient
      should be taught to use emollients and to avoid skin dryness and vasodilatation
      by contact with irritants. Topical anti-itch preparations can be recommended not
      only for treatment of localized pruritus, but also for therapy of generalized
      pruritus when general measures are not effective, systemic drugs are
      contraindicated, and/or as addition to causative or systemic therapy. Topical
      anti-itch preparations should be prescribed after the diagnosis is made and used
      as the first-choice treatment together with general measures.

PMID- 16297008
TI  - Ultraviolet phototherapy for pruritus.
AB  - Ultraviolet-based therapy has been used to treat various pruritic conditions
      including pruritus in chronic renal failure, atopic dermatitis, HIV, aquagenic
      pruritus and urticaria, solar, chronic, and idiopathic urticaria, urticaria
      pigmentosa, polycythemia vera, pruritic folliculitis of pregnancy, breast
      carcinoma skin infiltration, Hodgkin's lymphoma, chronic liver disease, and
      acquired perforating dermatosis, among others. Various mechanisms of action for
      phototherapy have been posited. Treatment limitations, side effects, and common
      dosing protocols are reviewed.

PMID- 16297009
TI  - Pruritus ani.
AB  - In the anal region, pruritus may be both idiopathic (mainly of
      psychological/psychiatric origin) and secondary to an underlying disorder or
      related to local causes (mainly of dermatologic interest). Persistent pruritus
      ani is, in particular, a challenging experience for the dermatologist.

PMID- 16297010
TI  - The future: critical knowledge about anti-itch therapy.
AB  - Itch is an extremely frequent and enervating symptom of many diseases. Current
      anti-itch therapy, which is based almost exclusively on an "immunocentric"
      viewpoint, is often unsatisfactory. Recent studies show that this symptom is in
      fact the result of a complex interplay among skin, nervous system, endocrine
      system, and immune system. This explains the frequent failure of therapeutic
      strategies focused only on a single factor and suggests the usefulness of a
      polypharmacologic symptomatic treatment, designed on a case-by-case basis as a
      result of a multidisciplinary approach. We discuss the perspectives of anti-itch
      therapy in light of the new pathogenetic and pharmacologic acquisitions.

PMID- 16297012
TI  - Cutaneous melanoma: estimating survival and recurrence risk based on
      histopathologic features.
AB  - The prognosis of melanoma is best understood in terms of a model of tumor
      progression, in which most melanomas may evolve through two major phases of
      progression: from a lesion that is nontumorigenic and has little or no capacity
      for metastasis; to a more advanced lesion that is tumorigenic and may have
      capacity for metastasis. The likelihood of metastasis varies with a number of
      attributes of the primary melanoma, including the phase of progression, the
      Breslow tumor thickness, mitotic rate, and host response to the tumorigenic
      compartment of the lesion, Clark's level of invasion, and other factors. When
      distant metastasis has occurred, the prognosis for the patient is very poor. In
      this monograph, the focus will be the discussion of factors related to the
      prognosis of melanomas that at diagnosis are clinically localized to the primary
      site.

PMID- 16297013
TI  - Cutaneous melanoma: methods of biopsy and definitive surgical excision.
AB  - The proper method of biopsy and definitive surgical excision of cutaneous
      melanoma is vital for optimal patient outcome. Clearly, the present authors'
      understanding of the pathophysiology of cutaneous melanoma continues to change at
      a rapid pace. Indeed, as the present authors' research efforts begin to expose
      some of the mysteries of melanoma, so do they begin to better understand the
      intricacies of this dreaded cancer. This article will highlight methods of biopsy
      for melanoma and the management of the primary tumor. The present authors review
      current recommendations for excision margins for the primary tumor, usefulness of
      lymphoscintigraphy, timing of definitive surgical excision, and issues unique for
      head and neck melanoma.

PMID- 16297016
TI  - Cutaneous melanoma: practical usefulness of the American Joint Committee on
      Cancer staging system.
AB  - The 2002 American Joint Committee on Cancer melanoma staging classification is
      the first to be based on natural history. Although primarily for hospital tumor
      registrars, knowledge of the classification is of value to dermatologists in
      prognosticating for their patients and in selecting candidates for sentinel node
      biopsy and possible subsequent therapies.

PMID- 16297015
TI  - Cutaneous melanoma: therapeutic lymph node and elective lymph node dissections,
      lymphatic mapping, and sentinel lymph node biopsy.
AB  - Early clinical observation in cancer patients suggested that tumors spread in a
      methodical, stepwise fashion from the primary site, to the regional lymphatics,
      and only then to distant locations. Based on these observations, the regional
      lymphatics were believed to be mechanical barriers, at least temporarily
      preventing the widespread dissemination of tumor. Despite evidence now available
      disputing its validity, this barrier theory has guided the surgical management of
      the regional lymphatics in cancer patients for more than a century, influencing
      the use of such surgical modalities as therapeutic lymph node dissection,
      elective lymph node dissection, and most recently lymphatic mapping and sentinel
      lymph node biopsy. No published randomized controlled trial exists that
      demonstrates improved overall patient survival for cancer of any type, including
      melanoma, after surgical excision of regional lymphatics. This article will
      review the biology of lymphatics as it relates to regional tumor metastasis, and
      based on available information, offer practical recommendations for the clinical
      dermatologist and their patients who have cutaneous melanoma.

PMID- 16297017
TI  - Cutaneous melanoma: baseline and ongoing laboratory evaluation.
AB  - Numerous laboratory tests and imaging methods are available that can be used in
      patients who are diagnosed with cutaneous melanoma. The downside risks related to
      testing are cost and patient anxiety. Therefore, it must be critically considered
      which examinations are useful and feasible. After a diagnosis of primary
      cutaneous melanoma, many physicians in Germany perform lymph node ultrasound to
      detect occult regional metastasis. Whole-body imaging techniques, except the
      physical examination, are unlikely to detect distant occult metastasis. In tumors
      that have an intermediate or high risk of recurrence (> 1 mm tumor thickness),
      baseline whole-body imaging may serve as a reference for ongoing evaluation.
      During follow-up care, physical examination alone is appropriate when there is a
      low risk for recurrence (up to 1-mm tumor thickness). In patients whose tumors
      are > 1 mm thickness, regular lymph node ultrasound examinations and
      determination of serum tumor marker S-100beta protein are commonly used by
      physicians in Germany. Whole-body imaging techniques are useful in patients who
      have locoregional and/or distant metastasis. For consideration of surgical
      resections in stage IV disease, more advanced examinations techniques such as
      positron emission tomography-computed tomography or whole body magnetic resonance
      imaging may be used. Early detection of limited disease using these methods may
      be helpful for patients who have locoregional metastases and for 10-20% of
      patients who have distant metastases and whose limited disease may be amenable to
      surgical resection.

PMID- 16297018
TI  - Cutaneous melanoma: surveillance of patients for recurrence and new primary
      melanomas.
AB  - The increasing incidence and overall survival of patients diagnosed with melanoma
      of the skin are leading to an ever-increasing population of individuals with a
      personal history of melanoma. These patients are at risk for developing local,
      regional, or distant recurrence and are also at greater risk than the general
      population for developing a new primary melanoma. This article presents the
      rational for implementing surveillance strategies for patients with a history of
      melanoma.

PMID- 16297019
TI  - The primacy of psychotherapy.

PMID- 16297021
TI  - "Dissed" by dating violence.
AB  - PROBLEM: This study describes the impact of the experience of dating violence on
      the daily lives of college women. METHODS: Qualitative content analysis was used
      to analyze transcribed responses from an open-ended question about the impact of
      dating violence. FINDINGS: Eight thematic categories emerged: emotional distress,
      distrust and using extra precautions, disconnected and distant in relationships,
      self-discontentment, disclaiming the experience, feeling disenfranchised, life
      disruption, and turning a situation from disempowering to empowering.
      CONCLUSIONS: Understanding the perspective of dating violence victims assists the
      advanced practice psychiatric nurse (APPN) with planning effective care. Routine
      screening about past and present experiences of violence must occur with all
      young women. Providers must be knowledgeable about available resources for
      victims.

PMID- 16297020
TI  - Computer addiction: implications for nursing psychotherapy practice.
AB  - TOPIC: Nurse psychotherapists will encounter the impact of today's technology on
      the daily lives of people including computer addiction. Computer addiction may
      also present with comorbidities such as depression, gambling, substance abuse,
      and marital infidelity and divorce. PURPOSE: This overview article presents what
      is currently documented in the literature regarding the incidence,
      symptomatology, and nursing psychotherapy interventions relevant to computer
      addiction and its treatment. Issues presented include computer addiction, virtual
      relationships, online marital infidelity, and compulsive online sexual behavior.
      SOURCES: Review of literature from Medline, Psychoinfo, CINAHL, and current
      texts. CONCLUSIONS: Given the increased use of computers in today's society,
      there is the potential for overuse of technology and neglect of others and self
      as a result of computer addiction. Computer disorders also present themselves as
      marital or couple discord with the potential for online extramarital affairs and
      compulsive sexual online behavior. A summary and an assessment tool are provided
      to guide the nurse psychotherapist in practice.

PMID- 16297022
TI  - Exploring the psychopathology of anorexia nervosa: a Mahlerian standpoint.
AB  - TOPIC: Anorexia nervosa is an eating disorder that extends beyond the well-known
      phenomenon of self-starvation to include dynamic psychological themes of autonomy
      and ego disturbances as well as self-regulation through eating disordered
      behaviors. PURPOSE AND SOURCE: Exploration of these themes within Mahler's (1975)
      object relational framework provides the opportunity to examine the genesis of
      these themes during early psychological ego development and how they may
      characterize the development of the anorectic experience. CONCLUSION: The
      Mahlerian perspective can provide psychiatric nursing with a psychoanalytical
      perspective outside of standard practice, thus promoting critical analysis and
      integration among the varying professions of psychiatry.

PMID- 16297023
TI  - Developing rational nursing actions: what's the problem with psychiatric nurses?

PMID- 16297024
TI  - The use of Reiki in psychotherapy.

PMID- 16297025
TI  - Antidepressant apathy syndrome.

PMID- 16297026
TI  - Mitigating cutaneous side effects of lamotrigine.

PMID- 16297031
TI  - The relationship between vertical craniofacial morphology and the sagittal path
      of mandibular movements.
AB  - The aim was to investigate the relationship between the vertical craniofacial
      morphology and the sagittal path of mandibular movements. The study was carried
      out in 40 subjects who were free of temporo-mandibular disorders. Mandibular
      movements and maximal jaw opening (MO) were recorded by means of a jaw tracking
      device. The opening-closing angle (OCA) was defined as the angle between the
      horizontal plane and the opening-closing path of movements. Vertical craniofacial
      morphology was assessed on prophile cephalograms by means of the Frankfort
      Mandibular Plane Angle (MP). The OCA did not differ between males and females
      (P>0.05). OCA and MP were negatively correlated (r=-0.62; P<0.001). MO was
      significantly greater in males that in females (P<0.05). MO was negatively
      correlated to MP (-0.44<r<-0.49; P<0.05). The findings suggest that the low-angle
      subjects exhibit a more vertical path of the mandibular movements than that of
      high-angle subjects. Differences in the sagittal path of jaw movements may be
      partly ascribed to anatomical factors.

PMID- 16297027
TI  - Bridging the gap.

PMID- 16297032
TI  - Surface EMG of jaw-elevator muscles and chewing pattern in complete denture
      wearers.
AB  - The aim of this study was to investigate the adaptation process of masticatory
      patterns to a new complete denture in edentulous subjects. For this purpose,
      muscle activity and kinematic parameters of the chewing pattern were
      simultaneously assessed in seven patients with complete maxillary and mandibular
      denture. The patients were analysed (i) with the old denture, (ii) with the new
      denture at the delivery, (iii) after 1 month and (iv) after 3 months from the
      delivery of the new denture. Surface electromyographic (EMG) signals were
      recorded from the masseter and temporalis anterior muscles of both sides and jaw
      movements were tracked measuring the motion of a tiny magnet attached at the
      lower inter-incisor point. The subjects were asked to chew a bolus on the right
      and left side. At the delivery of the new denture, peak EMG amplitude of the
      masseter of the side of the bolus was lower than with the old denture and the
      masseters of the two sides showed the same intensity of EMG activity, contrary to
      the case with the old denture. EMG amplitude and asymmetry of the two masseter
      activities returned as with the old denture in 3 months. The EMG activity in the
      temporalis anterior was larger with the old denture than in the other conditions.
      The chewing cycle width and lateral excursion decreased at the delivery of the
      new denture and recovered after 3 months.

PMID- 16297033
TI  - Contingent negative variation elicited before jaw and tongue movements.
AB  - Contingent negative variation (CNV) is a negative brain potential occurring
      between two successive stimuli when the first stimulus is a warning and the
      second stimulus requires a motor response. The CNV is interpreted as an
      expression of the cognitive processes in preparation for a response directed to a
      purpose. Using 19 electrodes we recorded CNVs for mouth opening, closing and
      lateral movements, tongue protrusion and hand extension in 10 healthy subjects.
      The aim of the study was to examine the motor control mechanism underlying jaw
      and tongue movements in a cognitive paradigm. The first stimulus (S1) served as a
      preparatory warning signal for the imperative stimulus (S2) 2 s after the S1. The
      subject performed the experimental tasks after the S2. The grand average CNVs for
      jaw and tongue movements showed a bilaterally widespread negativity with the
      maximum in the vertex region (Cz). The early CNV was identified about 400 ms
      after the S1 and its amplitude was highest at the midline-frontal area. The late
      CNV started approximately 1000 ms after the S1 with the maximum at Cz. The mean
      amplitude was significantly lower for hand extension than for the other tasks,
      and significantly higher for lateral movement than for mouth closing, suggesting
      that the CNV amplitude can be affected by the complexity of the task. The CNV
      recording may provide a means to study the neuronal activity necessary for the
      sensorimotor integration of jaw and tongue movements.

PMID- 16297034
TI  - Infantile reflexes and their effects on dental caries and oral hygiene in
      cerebral palsy individuals.
AB  - The aim of this study was to evaluate the presence of pathological primitive
      reflexes and their effects on dental caries and oral hygiene in cerebral-palsied
      individuals. A group of 124 non-institutionalized patients (57 males) attending
      Lar Escola Sao Francisco Rehabilitation Center, who had a medical diagnosis of
      spastic CP (age range 3-17 years, mean+/-s.d.=8.6+/-4.3) were selected for dental
      clinical evaluation according to WHO (Oral health surveys: basic methods, WHO,
      Geneva, 1997) and oral hygiene using the oral hygiene index proposed by Greene
      and Vermillion (J Am Dent Assoc, 1964, 68, 7). The presence/absence of the
      pathological primitive oral reflexes of rooting, suckle-swallow, biting and
      gagging was evaluated by observing patients' reaction after a stimulus. Results
      were statistically analysed by Fisher's exact, Chi-square and Kruskal-Wallis
      tests. A significantly higher percentage of the biting reflex in patients with
      quadriplegia was observed, and also the absence of this reflex in patients with
      hemiplegia (P=0.006). Patients with hemiplegia presented significantly lower DMF
      index values. Kruskal-Wallis test showed no statistical difference (P=0.335;
      0.677; 0.202) for OHI-S among the quadriplegia, diplegia and hemiplegia for all
      dentitions. Our data suggest that the more severe the neurological damage is, the
      more frequent is the presence of the biting reflex and consequently, the higher
      is the risk of oral diseases in this population due to the difficulty to perform
      an adequate oral hygiene.

PMID- 16297035
TI  - Intra-oral temperatures during function.
AB  - There has been limited published research assessing the range of oral temperature
      that the dental hard and soft tissues are exposed to. The temperatures that tooth
      structure and dental restorations encounter affect the performance of dental
      materials within the oral environment. This study therefore assessed the range of
      temperatures that a selected group could tolerate when drinking and also assessed
      the range of temperatures encountered in various intra-oral sites. These
      temperature fluctuations are for very brief periods of time but have a wide and
      varied range. Miniature dataloggers allowed for accurate measurements and
      recording of temperature from selected sites. The range of temperature recorded
      amongst the individuals tested shows the protection afforded to the dental hard
      tissues by the soft tissues of the oral cavity. The maximum and minimum mouth
      temperatures recorded show that hot fluids can raise the intra-oral temperature
      of the front teeth to around 70 degrees C and the consumption of iced drinks
      lowers the same teeth to around 0 degrees C. The range of temperature of hot
      fluids that can be tolerated by a selected group vary, but this does not seem to
      be the case for cold fluids. The thermistor beads mounted on the buccal surface
      of the lower front teeth and the palatal of the upper front teeth are exposed to
      the greatest temperature fluctuations during drinking fluids from a cup. The
      importance of these temperatures recorded in terms of dental materials testing
      and the role of material conductivity warrants further investigation.

PMID- 16297036
TI  - A study of the proximity of the Broadrick ideal occlusal curve to the existing
      occlusal curve in dentate patients.
AB  - Increasingly, clinicians are called upon to restore dentitions, which have become
      mutilated because of tooth loss, wear, trauma and disease. In many cases,
      restoration of the occlusal plane may be required. A simple tool, which provides
      the laboratory technician with an approximation of the patient's original
      occlusal curve may be useful. The purpose of this study is to determine the
      accuracy of the occlusal curve designed using the Broadrick flag. A total of 100
      patients with intact dental arches were examined, and deviations from the
      Broadrick curve were measured on scanned study models using a software package.
      Simple descriptive statistics were used to investigate the data, and intra
      examiner reliability was examined using a Bland Altman plot. The results
      demonstrated little deviation from the Broadrick curve in natural adult
      dentitions, mean deviation 0.1262 mm, 95% confidence interval -0.32 to 0.2844.
      Good intra-examiner reliability was achieved. It can be concluded that the
      Broadrick flag method may be of use in determining an appropriate occlusal curve
      for dentate individuals with deranged occlusal planes.

PMID- 16297037
TI  - Quality of communication between dental practitioners and dental technicians for
      fixed prosthodontics in Ireland.
AB  - The aim of this investigation was to examine the quality of communication between
      dental practitioners and dental technicians for fixed prosthodontics in Ireland.
      A pre-piloted questionnaire was distributed to large commercial laboratories in
      Ireland. Information was sought relating to the quality of written instructions
      and use of impression trays and materials for two forms of fixed prosthodontics-
      full veneer porcelain-fused-to-metal crowns (PFMs), and conventional fixed
      partial dentures (FPDs). Information was received relating to 241 items (145
      PFMs, 96 FPDs). All items were funded privately. Using pre-determined grading
      criteria, poor or no written instructions were provided in 55% of cases examined
      (n=128). Fifty-four per cent of master impressions were (n=129) made using a
      plastic stock tray. Three-quarters of written instructions for FPDs (n=73) did
      not specify the number of pontics to be included in its design. Despite the
      existence of various legal and ethical guidelines relating to the prescription
      and fabrication of fixed prostheses, more than one-half of the written
      instructions and master impressions examined in this study were inadequate.

PMID- 16297038
TI  - How light source and product shade influence cure depth for a contemporary
      composite.
AB  - Directly placed light activated resin based composite restorations are becoming
      increasingly popular for restoring cavities in posterior teeth. Marketing and
      patient as factors well as operator preference are behind this trend. Achieving
      adequate depth of cure is critical to the success of these restorations. Recently
      a number of second generation light emitting diode (LED) light activation units
      have been marketed and the manufacturer of one of these claims that it is capable
      of curing in half the time of its predecessor. This study tested that claim using
      a companion composite from the same manufacturer. The relationship between cure
      depth, shade changes on curing and opacity were also assessed. Under the
      limitations of the current investigation the results indicated that the second
      generation LED unit in question met the manufacturer's claim for halving cure
      time. Depths of cure approached those of a control halogen unit in half the 40 s
      radiation time of the latter. For the product tested depth of cure is strongly
      linked to material opacity.

PMID- 16297040
TI  - The end of the beginning.

PMID- 16297041
TI  - Skeletal muscle blood flow in anaesthetized horses. Part I: measurement
      techniques.
AB  - OBJECTIVE: The objective of this review was to describe the methodology and
      limitations of techniques that have been used to measure skeletal muscle blood
      flow in anaesthetized horses. DATABASE USED: Pubmed, personal files. CONCLUSION:
      Numerous techniques have been used in horses to study skeletal muscle blood flow
      during anaesthesia and after the administration of vasoactive agents. Of the
      available techniques, blood flow measurements are limited to either microvascular
      flow (radioactive xenon, laser Doppler flowmetry) or total blood flow
      (radioactive microspheres, electromagnetic flowmetry, Doppler ultrasonography).
      None of the techniques currently available are able to fully assess the
      distribution of flow throughout the skeletal muscle. Near-infrared spectroscopy
      has the potential to assess the adequacy of oxygenation within muscles; however,
      this technique is not without limitations, and more work is required to assess
      its suitability. Understanding the limitations of these techniques is an
      important prerequisite to the critical evaluation of the information currently
      available on the effects of anaesthesia and vasoactive drugs on skeletal muscle
      blood flow.

PMID- 16297042
TI  - Skeletal muscle blood flow in anaesthetized horses. Part II: effects of
      anaesthetics and vasoactive agents.
AB  - OBJECTIVE: This review aims at evaluating studies investigating the effects of
      anaesthesia on skeletal muscle blood flow and associated cardiovascular function
      in anaesthetized horses and discusses how the results of these studies contribute
      to our understanding of the pathogenesis and prevention of post-anaesthetic
      myopathy. DATABASE USED: Pubmed & personal files. CONCLUSION: There is little
      published information on the effects of anaesthesia on skeletal muscle blood flow
      in horses. Available reports predominantly refer to halothane and isoflurane. The
      effects of vasoactive drugs have mainly been studied in halothane-anaesthetized
      horses. The results of these studies support the importance of cardiac output in
      the maintenance of adequate arterial blood pressure, perfusion pressure and
      muscle blood flow. Adequate perfusion pressure appears to be important for
      overcoming the detrimental effects of high intra-compartmental pressure in
      dependent muscles and hydrostatic pressure in nondependent muscles.

PMID- 16297043
TI  - High inspired oxygen concentrations increase intrapulmonary shunt in
      anaesthetized horses.
AB  - OBJECTIVES: To compare pulmonary function and gas exchange in anaesthetized
      horses during and after breathing either O2-rich gas mixtures or air. ANIMALS:
      Six healthy standard bred trotters (age range 3-12 years; mass range 423-520 kg),
      four geldings and two mares. Study design Randomized, cross-over experimental
      study. METHODS: Horses were anaesthetized on two occasions with tiletamine
      zolazepam after pre-anaesthetic medication with acepromazine, romifidine and
      butorphanol. After endotracheal intubation and positioning in left lateral
      recumbency, animals were allowed to breathe spontaneously. One of two, randomly
      allocated inspired gas treatments was provided: either i) room air (fractional
      concentration of inspired O2 [FIO2] = 0.21) provided throughout anaesthesia; or
      ii) an O2-rich gas mixture (FIO2 = >0.95) for 15 minutes, followed by room air.
      The alternative treatment was delivered at the second anaesthetic. Respiratory
      and haemodynamic variables and the distribution of ventilation-perfusion (VA/Q)
      ratios (using the multiple inert gas elimination technique) were determined in
      the standing conscious horse (baseline) after sedation and during anaesthesia.
      RESULTS: Breathing O2-rich gas was associated with a decreased respiratory rate
      (p = 0.015) increased PaCO2 (p < 0.001) and increased PaO2 (p = 0.004) compared
      with breathing air. All horses developed intrapulmonary shunt during anaesthesia,
      but shunt was significantly greater (13 +/- 5%) when O2-rich gas was delivered
      compared with air breathing (5 +/- 2%; p = 0.013). Ten minutes after O2-rich gas
      was replaced by air, shunt remained larger in horses that had initially received
      oxygen compared with those breathing air (p = 0.042). Mixed venous oxygen
      tensions were significantly lower during sedation than at baseline (p < 0.001)
      and during anaesthesia (p < 0.001). CONCLUSIONS: During dissociative anaesthesia,
      arterial oxygenation was greater when horses breathed gas containing more than
      95% oxygen, compared with when they breathed air. However, breathing O2-rich gas
      increased intrapulmonary shunt and caused hypoventilation. The intrapulmonary
      shunt created during anaesthesia by high inspired O2 concentrations remained
      larger when FIO2 was reduced to 0.21, indicating that absorption atelectasis
      produced during O2-rich gas breathing persisted throughout anaesthesia. CLINICAL
      RELEVANCE: In healthy horses undergoing short-term dissociative anaesthesia, air
      breathing ensures a level of oxygen delivery that meets tissue demand. There is
      no benefit to horses in breathing O2-rich gas after the gas supply is
      discontinued. On the contrary, the degree of shunt induced by breathing O2-rich
      gas persists. The clinical relevance of this during recovery requires
      investigation.

PMID- 16297044
TI  - Total intravenous anaesthesia in horses using medetomidine and propofol.
AB  - OBJECTIVE: To examine the clinical suitability of medetomidine-propofol infusions
      for total intravenous anaesthesia in horses. ANIMALS: Fifty client-owned horses
      of mixed breed, age [mean +/- SD (range)] 6.6 +/- 4.4 (0.04-18) years, mass 478
      +/- 168.3 (80-700) kg presented for a range of operations requiring general
      anaesthesia. MATERIALS AND METHODS: Pre-anaesthetic medication was intravenous
      (IV) medetomidine 7 mug kg(-1). Anaesthesia was induced with IV ketamine (2 mg
      kg(-1)) and diazepam (0.02 mg kg(-1)). After endotracheal intubation, O2 was
      delivered (FiO2 > 0.85). Positive pressure ventilation was initiated if breath
      holding in excess of 1 minute occurred. Anaesthesia was maintained with a
      constant rate medetomidine infusion (3.5 microg kg(-1) hour(-1)) and propofol
      infused IV to effect (initial dose 0.1 mg kg(-1) minute(-1)). Heart (HR)
      respiratory (fr) and propofol administration rates, and systemic arterial blood
      pressures were recorded at 5-minute intervals. Arterial blood gas (O2 and CO2)
      tensions and pH values were recorded every 15 minutes. Ten minutes after ending
      medetomidine-propofol infusion, medetomidine (2 microg kg(-1); IV) was given.
      Cardiopulmonary data were analysed using descriptive statistical techniques.
      RESULTS: Thirty-three orthopaedic, seven integumentary and 10 elective abdominal
      operations were performed. Cardiopulmonary data, presented as range of mean
      individual (and absolute individual minimum and maximum values) were: HR: 28.0
      39.2 (16-88) beats minute(-1); mean arterial blood pressure: 74.0-132.5 (42-189)
      mmHg; PaO2: 22.1-42.9 (4.9-67.8) kPa; [166-322 (37-508) mmHg], PaCO2: 6.7-8.1
      (4.2-11.8) kPa [50-61 (32-88) mmHg] and pH 7.35-7.39 (7.15-7.48). Positive
      pressure ventilation was required in 23 horses. In three horses, HR values below
      20 beats minute(-1) were treated with 20 microg kg(-1) atropine (IV). Mean
      propofol infusion rates were 98-108 microg kg(-1) minute(-1). During anaesthesia,
      movement occurring in 14 horses was controlled with thiopental. Duration of
      anaesthesia was 111.6 +/- 41.4 (46-225) minutes. Recovery in all horses was
      uneventful and completed within 42.2 +/- 19.8 (12-98) minutes. CONCLUSIONS AND
      CLINICAL RELEVANCE: Medetomidine-propofol infusion produces adequate conditions
      for a range of surgical procedures. Cardiovascular function was adequate, as no
      pressor agents were required. Positive pressure ventilation was required in 23
      horses.

PMID- 16297045
TI  - Cardiopulmonary effects of desflurane in horses.
AB  - OBJECTIVE: To determine the cardiopulmonary effects of desflurane (DES) in
      horses. ANIMALS: Six healthy adult horses, three males and three females, aged 9
      +/- 4 (mean +/- SD) years and weighing 370 +/- 36 kg. MATERIALS AND METHODS:
      Anaesthesia was induced with an O2 (10 L minute(-1)) and DES mixture (vaporizer
      setting 18%). After oro-tracheal intubation, horses were positioned in right
      lateral recumbency. Anaesthesia was maintained with DES in O2 (20 mL kg(-1)
      minute(-1)) delivered through a large animal circle breathing system. The minimum
      alveolar concentration of DES (MAC(DES)) that prevented purposeful movement in
      response to 60 seconds of electrical stimulation of the oral mucous membranes was
      determined for each horse. The delivered concentration of DES was then increased
      to achieve end-tidal concentrations corresponding to 1.5 x MAC(DES), 1.75 x
      MAC(DES), and 2.0 x MAC(DES). Heart rate (HR), mean arterial blood pressure
      (MAP), respiratory rate (fr), tidal volume (VT), minute volume (VM) and core
      temperature were determined, and blood samples for arterial blood gas analysis
      taken at each DES concentration. All data were analysed by two-way anova for
      repeated measures and Fisher's test for multiple comparisons. A probability level
      of p < 0.05 was applied. RESULTS: Desflurane concentrations of 2.0 x MAC(DES)
      increased HR whereas lower concentrations did not. Mean arterial pressure was not
      affected by 1.0 x MAC(DES) 1.5 x MAC(DES) or 1.75 x MAC(DES), whereas it
      decreased at 2.0 x MAC(DES). All concentrations of DES examined significantly
      depressed fr, VT and VM. CONCLUSIONS AND CLINICAL RELEVANCE: Desflurane
      concentrations between 1.0 and 1.75 x MAC(DES) reduces fr and VM but does not
      affect HR or MAP in horses.

PMID- 16297046
TI  - Comparison of two thiopental infusion rates for the induction of anaesthesia in
      dogs.
AB  - OBJECTIVE: To compare the induction dose requirements of thiopental using two
      different infusion rates for induction of anaesthesia in dogs. STUDY DESIGN:
      Prospective, randomized study. ANIMALS: Fifty, healthy (ASA I or II) client-owned
      dogs with a mean age of 4.1 years and a mean mass of 20.4 kg undergoing elective
      surgery. MATERIALS AND METHODS: Animals were randomly assigned to receive an
      infusion of 2.5% thiopental at a rate of either 0.1 ml kg(-1) minute(-1) or 0.4
      ml kg(-1)minute(-1), 30-40 minutes after pre-anaesthetic medication with
      intramuscular acepromazine (0.025 mg kg(-1)) and pethidine (3.5 mg kg(-1)).
      Thiopental administration was controlled by a precision syringe driver.
      Statistical analyses of the results, using the outcome 'mg kg(-1) required for
      induction' (log-transformed) included unpaired t-tests for all categorical data
      (thiopental infusion rate, breed, sex, obesity, sedation quality) and univariable
      linear regression for continuous variables (mass, age). All variables were then
      considered in a multivariable linear regression model. The quality of induction
      with the two different infusion rates was also assessed. RESULTS: After
      controlling for quality of sedation, the thiopental induction dose requirement
      was significantly less (p < 0.001) with the slower infusion rate (median = 7.5 mg
      kg(-1); range 4.9-13.7) compared with the faster infusion rate (median =11.0 mg
      kg(-1); range 6.6-18.0). The quality of sedation also affected the dose required
      (p = 0.03). The slower infusion rate was associated with a significantly poorer
      induction quality (p = 0.03) [corrected] CONCLUSIONS: Slow thiopental infusion
      (0.1 ml kg(-1) minute(-1)) for anaesthesia induction after acepromazine/pethidine
      pre-anaesthetic medication reduced the induction dose requirement, although the
      quality of induction was inferior. CLINICAL RELEVANCE: The induction dose of
      thiopental was reduced with a slower administration rate and so slow
      administration is recommended in thiopental-sensitive animals.

PMID- 16297048
TI  - Factors affecting the sequence of manuscript publication.

PMID- 16297049
TI  - Health-related quality of life of living kidney donors: review of the short form
      36-health questionnaire survey.
AB  - Kidney transplantation is the ultimate goal and the best treatment for most
      patients with end-stage renal disease. Organ shortage and steadily growing
      waiting time for a cadaver kidney transplant have forced the medical community to
      look for alternatives, such as living kidney donation. However, available data
      examining health-related quality of life (QOL) issues of living donors are
      currently limited. In addition, little information regarding factors associated
      with health-related QOL in living kidney donors is currently available and this
      issue remains controversial. This review article aims to summarize the data
      regarding health-related QOL of living kidney donors by using the Medical
      Outcomes Study Short Form.

PMID- 16297047
TI  - The use and assessment of ketamine-medetomidine-butorphanol combinations for
      field anaesthesia in wild European badgers (Meles meles).
AB  - OBJECTIVE: To evaluate the effectiveness of four ketamine-based anaesthetics in
      badgers using a quantitative anaesthesia assessment technique. STUDY DESIGN:
      Prospective randomized 'blinded' experimental trial. METHODS: The quality of
      induction, of anaesthesia (at 5-minute intervals) and of recovery were assessed
      in 93 badgers, given either one of three ketamine (K)-medetomidine (M)
      butorphanol (B) combinations: group A - M K B at 20/40/80 microg kg(-1); group B 
      M K B at 20/40/60 microg kg(-1); and group C - M K B at 20/60/40 microg kg(-1),
      or ketamine (K) alone at 2 mg kg(-1) (group D). The assessor was ignorant of the
      combination administered. Physiological variables (heart and respiratory rates
      and rectal temperature) were measured at 5-minute intervals during anaesthesia.
      Gingival mucus membrane colour was also recorded. RESULTS: Induction to
      anaesthesia was most rapid with ketamine (2 mg kg(-1)) although induction quality
      did not differ between techniques. Ketamine used alone gave the poorest score for
      anaesthesia quality. Heart rate (HR) and scores for gingival mucus membrane
      colour were higher in animals anaesthetized with ketamine alone. Rectal
      temperature did not differ significantly between the techniques at any time
      during anaesthesia. Ketamine used alone produced the poorest quality of recovery.
      CONCLUSION AND CLINICAL RELEVANCE: The M-K-B combinations investigated overcame
      several side effects associated with ketamine anaesthesia, but at the expense of
      more variable induction times, lower HRs, and poorer mucus membrane coloration.

PMID- 16297050
TI  - A prospective study comparing cytomegalovirus antigenemia, DNAemia and RNAemia
      tests in guiding pre-emptive therapy in thoracic organ transplant recipients.
AB  - We evaluated the usefulness of DNAemia and mRNAemia tests in guiding the pre
      emptive therapy against cytomegalovirus (CMV) infections in thoracic organ
      transplant recipients using antigenemia test as the reference. Seven lung (LTR)
      and 14 heart (HTR) transplant recipients were prospectively monitored for CMV by
      antigenemia, DNAemia (Cobas Amplicor PCR Monitor) and pp67-mRNAemia (NASBA)
      tests. However, only the antigenemia test guided pre-emptive therapy with cut-off
      levels of >or=2 and >or=5-10 pp65-positive leukocytes/50 000 leukocytes in the
      LTRs and HTRs, respectively. CMV DNAemia was detected in 26/28 (93%) and RNAemia
      in 17/28 (61%) of the CMV antigenemias requiring antiviral therapy (P = 0.01).
      Optimal DNAemia levels (sensitivity/specificity) estimated from receiver
      operating characteristic curve to achieve maximal sum of sensitivity and
      specificity were 400 (75.9/92.7%), 850 (91.3/91.3%) and 1250 (100/91.5%)
      copies/ml for the antigenemia of 2, 5 and 10 pp65-positive leukocytes,
      respectively. The sensitivities of nucleic acid sequence-based amplification
      (NASBA) were 25.9%, 43.5% and 56.3% in detecting the same cut-off levels of
      antigenemia. In thoracic organ transplant recipients, the Cobas PCR assay is
      comparable with the antigenemia test in guiding pre-emptive therapy against CMV
      infections when threshold levels of over 5 pp65-antigen-positive leukocytes are
      used as the reference. In contrast, the low sensitivity of NASBA limits its
      usefulness in the guidance of pre-emptive therapy.

PMID- 16297051
TI  - The first one thousand liver transplants in Turin: a single-center experience in
      Italy.
AB  - The first Italian liver transplant center to reach the goal of 1000 procedures
      was Turin. The paper reports this single-center experience, highlighting the main
      changes that have occurred over time. From 1990 to 2002, 1000 consecutive liver
      transplants were performed in 910 patients, mainly cirrhotics. Surgical technique
      was based on the preservation of the retrohepatic vena cava of the recipient. The
      veno-venous bypass was used in 30 cases only and abandoned since 1997. Operating
      time, warm ischemia time and length of hospital stay significantly decreased over
      the years, while operating room extubation became routine. Immunosuppression
      pivoted on cyclosporine A. Management of retransplantations, marginal grafts, and
      of HCV-positive, HBV-positive and hepatocellular carcinoma recipients were
      optimized. Median follow-up of the patients was 41 months. Overall survival rates
      at 1, 5 and 10 years were 87%, 78% and 72% respectively. Survival rates obtained
      in the second half of the cases (1999-2002 period) were significantly better than
      those obtained in the first half (1990-1998 period) (90% vs. 83% at 1 year and
      81% vs. 76% at 5 years respectively). Increasing experience in liver transplant
      surgery and postoperative care allowed standardization of the procedure and
      expansion of the activity, with parallel improvement of the results.

PMID- 16297052
TI  - A prospective randomized trial comparing tacrolimus and steroids with tacrolimus
      monotherapy in liver transplantation: the impact on recurrence of hepatitis C.
AB  - The aim of this prospective randomized trial was to study the efficacy and safety
      of tacrolimus monotherapy (TACRO) and compare it with our standard treatment of
      tacrolimus plus steroids (TACRO + ST) after liver transplant (LT). Furthermore,
      the impact of steroid-free immunosuppression on outcome of hepatitis C virus
      (HCV) was analysed. Between 1998 and 2000, 60 patients (mean age: 57 years) were
      included in the study and randomized to receive TACRO (n = 28) or TACRO + ST (n =
      32). Indication for LT was postnecrotic cirrhosis in all cases (58.3% were HCV
      positive). Mean follow-up was 44 months. Survival, incidence of rejection,
      infection and side-effects were compared between the two groups. In patients with
      HCV infection, incidence and severity of acute hepatitis C, long-term outcome of
      recurrent hepatitis C and survival were studied in an intention-to-treat analysis
      or in the real group analysis (real-TACRO versus real-TACRO + ST). Patient
      survival at 1, 3 and 5 years, tacrolimus pharmacokinetics, incidence of rejection
      infections and side-effects were similar. In patients with HCV, the incidence and
      severity of graft hepatitis C tended to be lower in TACRO (47%) compared with
      TACRO + ST (67%) (P = NS), and also in real-TACRO (42%) compared with real-TACRO
      + ST (61%) (P = NS). A poor outcome considered as evolution to cirrhosis at 3
      years was observed in one (9%) living patient in real-TACRO and nine (45%) in
      real-TACRO + ST (P = 0.04). Patient survival at 1, 3 and 5 years was 92%, 92% and
      73% for real-TACRO and 78%, 61% and 51% for real TACRO + ST (P = 0.07). Steroid
      free immunosuppression appears to be safe and efficacious. The main advantage of
      this regimen could be in HCV patients, as recurrence of hepatitis in the graft
      was less severe in the group of patients in whom steroids could be avoided
      completely.

PMID- 16297053
TI  - Femoral arteries energy dissipation and filtering function remain unchanged after
      cryopreservation procedure.
AB  - The aim was to evaluate our cryopreservation method effects on the mechanical
      properties and filtering function of human superficial femoral arteries (SFA).
      SFA segments from 10 multiorgan donors were divided into two groups: fresh,
      tested 24-48 h after harvesting, and cryopreserved/defrosted, tested after 1
      month of cryopreservation. The cooling process was carried out in three steps: 2
      degrees C/min until -40 degrees C; 5 degrees C/min until -90 degrees C and
      finally a rapid cooling by transferring the bag to vapour phase of liquid
      nitrogen (-142 degrees C). Thawing was made in two steps, a slow warming time by
      exposing the bag to 20 degrees C during 20 min, followed by a rapid warming by
      immersion in a 40 degrees C warm bath until defrost. In a circulation mock,
      arterial pressure [Pressure signal (P)] and diameter [Diameter (D)] were
      registered at similar stretch-frequency, P and flow levels. A compliance transfer
      function (D/P) was used for the on-line assessment of the arterial wall elastic
      (E), viscous (eta), and inertial (M) properties. To evaluate the arterial wall
      filter function, the arterial wall D/P frequency response was characterized, the
      cut-off frequency (fc) was quantified, and the viscous energy dissipation (Weta)
      was calculated. After cryopreservation, there were not significant changes in E,
      eta, M, Weta, and fc.

PMID- 16297054
TI  - Early morbidity after pancreas transplantation.
AB  - This study aims to evaluate and compare the early outcome of both pancreas-alone
      transplantation (PTA) and simultaneous kidney-pancreas transplantation (SPKT)
      focusing on the complications affecting the first month after the procedures. The
      records of all patients who underwent PTA or SPKT were reviewed. We considered
      the length of ICU stay, the need for postoperative ventilatory support,
      hemodynamic and metabolic data (arterial pH, serum glucose, need for exogenous
      insulin), infectious diseases incidence, microbiological colonization rate and
      any kind of postoperative complication arising during the first month after the
      transplantation. PTA recipients underwent a quicker surgery (P < 0.01) with
      shorter ICU stay (P < 0.05) and a lower need for postoperative mechanical
      ventilation (P < 0.05). They also had a higher hemodynamic stability (P < 0.05)
      with less cardiological complications (P < 0.05) in the intra- and postoperative
      phases; bacterial colonisation was also less frequent in PTA recipients (P <
      0.05). On the contrary, no significant difference was noted with regard to
      postoperative nausea/vomiting, sudden myocardial death, ICU re-admissions, graft
      function, rate of rejection, grafts explantation and re-transplantation. PTA
      could be considered as preemptive for severe diabetic complications in patients
      with long-lasting severe type I diabetes. However, establishing the correct
      timing of PTA is of paramount importance in order not to expose the patients
      early to risks arising from a major surgery and heavy immunosuppressive
      treatments.

PMID- 16297055
TI  - Insulin and islet autoantibodies after pancreas transplantation.
AB  - Autoimmune recurrence and subsequent diabetes after pancreas transplantation has
      been described. In this cross-sectional study 91 type 1 diabetic patients were
      examined after successful pancreas/kidney transplantation (SPK). We studied the
      prevalence of autoantibodies to insulin (IAA), glutamate decarboxylase (GAD) and
      tyrosine phosphatase (IA-2) as well as parameters of pancreas graft function.
      Graft recipients were grouped according to immunoreactivity: group 1: no
      immunoreactivity; group 2: immunoreactivity to one antigen; group 3:
      immunoreactivity to two or three antigens. Twenty-five percent of graft
      recipients displayed no immunoreactivity, 39% displayed positivity for one
      antigen and 36% were positive for two or three antigens. There were no
      significant differences concerning fasting glucose, HbA1(c), glucose tolerance
      and renal function between the groups. Patients with cyclosporine (n = 42) as
      first-line immunosuppression displayed more often immunoreactivity to IA-2 and
      IAA than patients treated with tacrolimus (n = 49) (31% vs. 14%, P = 0.04; 67%
      vs. 47%, P = 0.04). In addition methylprednisolone therapy was related to less
      immunoreactivity to IA-2. Immunological markers for type 1 diabetes can be
      determined in the majority of pancreas graft recipients despite adequate
      immunosuppression. However, immunoreactivity was not associated with impaired
      graft function. Patients with cyclosporine for immunosuppression and withdrawal
      of glucocorticoids therapy were more often immunoreactive to IAA and IA-2.

PMID- 16297056
TI  - The effect of anti-lymphocyte serum on subpopulations of blood and tissue
      leucocytes: possible supplementary mechanisms for suppression of rejection and
      the development of opportunistic infections.
AB  - Xenogeneic anti-lymphocyte serum (ALS) remains a major reagent for
      immunosuppression in clinical practice, but mechanisms of action and risks of
      opportunistic infection have not been considered in the context of innate
      immunity and its role in immune responsiveness. Rabbit anti rat ALS was
      administered intraperitoneally. Blood was taken for flow cytometry to establish
      absolute counts of leucocyte subsets. Tissues were harvested for immunohistology
      to evaluate interstitial dendritic cells and tissue macrophages. At day 2 of ALS
      therapy, T cells are completely depleted, as anticipated. B cells are
      undiminished and form approximately 90% of blood leucocytes. Monocytes and
      natural killer (NK) cells are substantially (approximately 80%), but not
      completely, depleted, and there is a trend for diminished numbers of putative
      dendritic cells. Neither interstitial dendritic cells nor tissue macrophages in
      heart are affected. The results at day 7 were very similar to day 2. Substantial
      depletion of blood monocytes and NK cells might attenuate the innate immune
      system, and represent a possible supplementary mechanism (in addition to T cell
      depletion) for suppression of rejection. It might be of particular importance in
      reducing defences against infections. Monitoring these parameters could be of
      clinical value.

PMID- 16297057
TI  - The use of autologous rectus facia sheath for replacement of inferior caval vein
      defect in orthotopic liver transplantation.
AB  - Occasionally, during liver transplantation, vascular reconstructions have to be
      performed. Donor vessels can be harvested for this purpose. However, when these
      are lacking, alternatives should be available. A possible alternative can be the
      use of autologous rectus fascia sheath, folded as a tube with the mesothelium on
      the inside. Earlier experimental studies from our centre showed the successful
      use of the rectus fascia sheath graft in vascular defects in animal experiments.
      This report describes the first use of this autologous tubular graft for
      replacement of the inferior caval vein interponate during liver transplantation
      in men.

PMID- 16297059
TI  - Vaginal bleeding complicating portal hypertension: a particular entity - report
      of two cases and review of the literature.
AB  - Vaginal haemorrhage arising from varices is an exceptional complication of portal
      hypertension. Two cases successfully treated by transjugular intrahepatic
      portosystemic stent shunt are presented here. Both these patients previously had
      a total hysterectomy as did three out of four cases reported in the literature.
      Clinicians should be aware of 'vaginal bleeding' in the context of both
      hysterectomy and chronic liver disease in order to adopt the correct diagnostic
      and therapeutic approach. Definitive treatment can be obtained only if the
      underlying portal hypertension is adequately taken into consideration.

PMID- 16297058
TI  - Chylous ascites as a complication of laparoscopic donor nephrectomy.
AB  - Laparoscopic living donor nephrectomy (LLDN) is a minimally invasive technique
      for kidney procurement and was developed with the hope of reducing the
      disincentives associated with live renal donation. Compared with open donor
      nephrectomy (ODN), this alternative has many advantages including less
      postoperative pain and earlier return to work. Unfortunately, these benefits are
      sometimes negated by postoperative complications. Among these, chylous ascites
      (CA) is a rare but serious problem that is usually managed conservatively. We
      report the case of a living donor who developed CA refractory to initial
      conservative management and surgical treatment. We also discuss the role of
      surgery in the treatment of CA following LLDN.

PMID- 16297060
TI  - Reconstruction of the middle hepatic vein in a modified right liver graft of
      living-donor liver transplantation while preserving the recipient's middle
      hepatic vein.

PMID- 16297061
TI  - Current practices of donor pancreas allocation in the UK: future implications for
      pancreas and islet transplantation.

PMID- 16297065
TI  - The immediate-early ethylene response gene OsARD1 encodes an acireductone
      dioxygenase involved in recycling of the ethylene precursor S-adenosylmethionine.
AB  - Methylthioadenosine (MTA) is formed as a by-product of ethylene biosynthesis from
      S-adenosyl-L-methionine (AdoMet). The methionine cycle regenerates AdoMet from
      MTA. In two independent differential screens for submergence-induced genes and
      for 1-aminocyclopropane-1-carboxylic acid (ACC)-induced genes from deepwater rice
      (Oryza sativa L.) we identified an acireductone dioxygenase (ARD). OsARD1 is a
      metal-binding protein that belongs to the cupin superfamily. Acireductone
      dioxygenases are unique proteins that can acquire two different activities
      depending on the metal ion bound. Ectopically expressed apo-OsARD1 preferentially
      binds Fe(2+) and reconstituted Fe-OsARD1 catalyzed the formation of 2-keto
      pentanoate and formate from the model substrate 1,2-dihydroxy-3-ketopent-1-ene
      and dioxygen, indicating that OsARD1 is capable of catalyzing the penultimate
      step in the methionine cycle. Two highly homologous ARD genes were identified in
      rice. OsARD1 mRNA levels showed a rapid, early and transient increase upon
      submergence and after treatment with ethylene-releasing compounds. The second
      gene from rice, OsARD2, is constitutively expressed. Accumulation of OsARD1
      transcript was observed in the same internodal tissues, i.e. the meristem and
      elongation zone, which were previously shown to synthesize ethylene. OsARD1
      transcripts accumulated in the presence of cycloheximide, an inhibitor of protein
      synthesis, indicating that OsARD1 is a primary ethylene response gene. Promoter
      analysis suggests that immediate-early regulation of OsARD1 by ethylene may
      involve an EIN3-like transcription factor. OsARD1 is induced by low levels of
      ethylene. We propose that early feedback activation of the methionine cycle by
      low levels of ethylene ensures the high and continuous rates of ethylene
      synthesis required for long-term ethylene-mediated submergence adaptation without
      depleting the tissue of AdoMet.

PMID- 16297064
TI  - Transcriptionally active transposable elements in recent hybrid sugarcane.
AB  - Transposable elements (TEs) are considered to be important components of the
      maintenance and diversification of genomes. The recent increase in genome
      sequence data has created an opportunity to evaluate the impact of these active
      mobile elements on the evolution of plant genomes. Analysis of the sugarcane
      transcriptome identified 267 clones with significant similarity to previously
      described plant TEs. After full cDNA sequencing, 68 sugarcane TE clones were
      assigned to 11 families according to their best sequence alignment against a
      fully characterized element. Expression was further investigated through a
      combined study utilizing electronic Northerns, macroarray, transient and stable
      sugarcane transformation. Newly synthesized cDNA probes from flower, leaf roll,
      apical meristem and callus tissues confirm previous results. Callus was
      identified as the tissue with the highest number of TEs being expressed,
      revealing that tissue culture drastically induced the expression of different
      elements. No tissue-specific family was identified. Different representatives
      within a TE family displayed differential expression patterns, showing that each
      family presented expression in almost every tissue. Transformation experiments
      demonstrated that most Hopscotch clone-derived U3 regions are, indeed, active
      promoters, although under a strong transcriptional regulation. This is a large
      scale study about the expression pattern of TEs and indicates that mobile genetic
      elements are transcriptionally active in the highly polyploid and complex
      sugarcane genome.

PMID- 16297066
TI  - RNA interference of Arabidopsis beta-amylase8 prevents maltose accumulation upon
      cold shock and increases sensitivity of PSII photochemical efficiency to freezing
      stress.
AB  - It has been suggested that beta-amylase (BMY) induction during temperature stress
      in Arabidopsis could lead to starch-dependent maltose accumulation, and that
      maltose may contribute to protection of the electron transport chain and proteins
      in the chloroplast stroma during acute stress. A time-course transcript profiling
      analysis for cold shock at 4 degrees C revealed that BMY8 (At4g17090) was induced
      specifically in response to cold shock, while major induction was not observed
      for any of the other eight beta-amylases. A parallel metabolite-profiling
      analysis revealed a robust transient maltose accumulation during cold shock. BMY8
      RNAi lines with lower BMY8 expression exhibited a starch-excess phenotype, and a
      dramatic decrease in maltose accumulation during a 6-h cold shock at 4 degrees C.
      The decreased maltose content was also accompanied by decreased glucose, fructose
      and sucrose content in the BMY8 RNAi plants, consistent with the roles of beta
      amylase and maltose in transitory starch metabolism. BMY8 RNAi lines with reduced
      soluble sugar content exhibited diminished chlorophyll fluorescence as F(v)/F(m)
      ratio compared with wild type, suggesting that PSII photochemical efficiency was
      more sensitive to freezing stress. Together, carbohydrate analysis and freezing
      stress results of BMY8 RNAi lines indicate that increased maltose content, by
      itself or together through a maltose-dependent increase in other soluble sugars,
      contributes to the protection of the photosynthetic electron transport chain
      during freezing stress.

PMID- 16297067
TI  - Mitochondria as a connected population: ensuring continuity of the mitochondrial
      genome during plant cell dedifferentiation through massive mitochondrial fusion.
AB  - Mitochondrial fusion in plants and its role in development are poorly understood.
      Cultured tobacco mesophyll protoplasts provide an excellent experimental system
      for visualizing mitochondrial dynamics. Before protoplasts first divide,
      mitochondria undergo a phase of extensive elongation before fission causes an
      increase in number, followed by actin filament (AF)-dependent dispersion that
      distributes mitochondria uniformly throughout the cytoplasm. Here, by fusing
      protoplasts containing either green fluorescent protein- or MitoTracker-labelled
      mitochondria, we show that elongation results from fusion during early (4-8 h)
      protoplast culture. This massive mitochondrial fusion (MMF) leads to near
      complete mixing of the mitochondrial population within 24 h. Staining isolated
      mitochondria with 4',6-diamidino-2-phenylindole (DAPI) revealed that in freshly
      prepared protoplasts mitochondrial nucleoids were unequally distributed, with
      many mitochondria failing to stain with DAPI, suggesting the presence of an
      incomplete mitochondrial genome. Following MMF, nucleoids were distributed evenly
      throughout the population, thereby ensuring continuity of the mitochondrial
      genome in daughter cells. Massive mitochondrial fusion appears to be specific to
      dedifferentiation, since it also occurs in mesophyll protoplasts of Arabidopsis
      and Medicago but not in protoplasts from already dedifferentiated cells such as
      BY-2 or callus cultures. Efficient MMF requires an inner membrane electrical
      gradient, cytoplasmic protein synthesis, microtubules and functional kinesin but
      not ATP or AFs, indicating fundamental differences from mitochondrial fusion in
      non-plant systems. Our studies reveal that individual mitochondria are connected
      over time by fusion events, a finding that allows a clearer interpretation of how
      novel mitochondrial genotypes develop following cell fusion, and indicates that
      developmentally regulated fusion ensures continuity of the mitochondrial genome.

PMID- 16297069
TI  - A loss-of-function mutation in AtYSL1 reveals its role in iron and nicotianamine
      seed loading.
AB  - The Arabidopsis Yellow Stripe 1-Like (YSL) proteins have been identified by
      homology with the maize (Zea mays) Yellow Stripe 1 (YS1) transporter which is
      responsible for iron-phytosiderophore (PS) uptake by roots in response to iron
      shortage. Although dicotyledonous plants do not synthesize PS, they do synthesize
      the PS precursor nicotianamine, a strong metal chelator essential for maintenance
      of iron homeostasis and copper translocation. Furthermore, ZmYS1 and the rice
      (Oryza sativa) protein OsYSL2 have metal-nicotianamine transport activities in
      heterologous expression systems. In this work, we have characterized the function
      of AtYSL1 in planta. Two insertional loss-of-function ysl1 mutants of Arabidopsis
      were found to exhibit increased nicotianamine accumulation in shoots. More
      importantly, seeds of both ysl1 knockouts contained less iron and nicotianamine
      than wild-type seeds, even when produced by plants grown in the presence of an
      excess of iron. This phenotype could be reverted by expressing the wild-type
      AtYSL1 gene in ysl1 plants. ysl1 seeds germinated slowly, but this defect was
      rescued by an iron supply. AtYSL1 was expressed in the xylem parenchyma of
      leaves, where it was upregulated in response to iron excess, as well as in pollen
      and in young silique parts. This pattern is consistent with long-distance
      circulation of iron and nicotianamine and their delivery to the seed. Taken
      together, our work provides strong physiological evidence that iron and
      nicotianamine levels in seeds rely in part on AtYSL1 function.

PMID- 16297068
TI  - Contrasting interactions between ethylene and abscisic acid in Rumex species
      differing in submergence tolerance.
AB  - Complete submergence of flooding-tolerant Rumex palustris plants strongly
      stimulates petiole elongation. This escape response is initiated by the
      accumulation of ethylene inside the submerged tissue. In contrast, petioles of
      flooding-intolerant Rumex acetosa do not increase their elongation rate under
      water even though ethylene also accumulates when they are submerged. Abscisic
      acid (ABA) was found to be a negative regulator of enhanced petiole growth in
      both species. In R. palustris, accumulated ethylene stimulated elongation by
      inhibiting biosynthesis of ABA via a reduction of RpNCED expression and enhancing
      degradation of ABA to phaseic acid. Externally applied ABA inhibited petiole
      elongation and prevented the upregulation of gibberellin A(1) normally found in
      submerged R. palustris. In R. acetosa submergence did not stimulate petiole
      elongation nor did it depress levels of ABA. However, if ABA concentrations in R.
      acetosa were first artificially reduced, submergence (but not ethylene) was then
      able to enhance petiole elongation strongly. This result suggests that in Rumex a
      decrease in ABA is a prerequisite for ethylene and other stimuli to promote
      elongation.

PMID- 16297070
TI  - Inward rectification of the AKT2 channel abolished by voltage-dependent
      phosphorylation.
AB  - The Arabidopsis K(+) channel AKT2 possesses the remarkable property that its
      voltage threshold for activation can be either within the physiological range
      (gating mode 1), or shifted towards considerably more positive voltages (gating
      mode 2). Gating mode 1 AKT2 channels behave as delayed K(+)-selective inward
      rectifiers; while gating mode 2 AKT2 channels are K(+)-selective 'open leaks' in
      the physiological range of membrane potential. In the present study we have
      investigated modulation of AKT2 current by effectors of phosphatases/kinases in
      COS cells and Xenopus oocytes. These experiments show that (i) dephosphorylation
      can result in AKT2 channel silencing; and (ii) phosphorylation by protein kinase
      A (PKA) favors both recruitment of silenced AKT2 channels and transition from
      gating mode 1 to gating mode 2. Interestingly, phosphorylation of AKT2 by PKA in
      COS cells and Xenopus oocytes is favored by hyperpolarization. Two PKA
      phosphorylation sites (S210 and S329) were pinpointed in the region of the pore
      inner mouth. The role of these phosphorylation sites in the switch between the
      two gating modes was assessed by electrophysiological characterization of mutant
      channels. The molecular aspects of AKT2 regulation by phosphorylation, and the
      possible physiological meaning of such regulation in the plant context, are
      discussed.

PMID- 16297071
TI  - Structure-function analysis of the plasma membrane- localized Arabidopsis defense
      component ACD6.
AB  - The ACCELERATED CELL DEATH 6 (ACD6) protein, composed of an ankyrin-repeat domain
      and a predicted transmembrane region, is a necessary positive regulator of
      Arabidopsis defenses. ACD6 overexpression confers enhanced disease resistance by
      priming stronger and quicker defense responses during pathogen infection, plant
      development or treatment with an agonist of the key defense regulator salicylic
      acid (SA). Modulation of ACD6 affects both SA-dependent and SA-independent
      defenses. ACD6 localizes to the plasma membrane and is an integral membrane
      protein with a cytoplasmic ankyrin domain. An activated version of ACD6 with a
      predicted transmembrane helix mutation called ACD6-1 has the same localization
      and overall topology as the wild-type protein. A genetic screen for mutants that
      suppress acd6-1-conferred phenotypes identified 17 intragenic mutations of ACD6.
      The majority of these mutations reside in the ankyrin domain and in predicted
      transmembrane helices, suggesting that both ankyrin and transmembrane domains are
      important for ACD6 function. One mutation (S638F) also identified a key residue
      in a putative loop between two transmembrane helices. This mutation did not alter
      the stability or localization of ACD6, suggesting that S635 is a critical residue
      for ACD6 function. Based on structural modeling, two ankyrin domain mutations are
      predicted to be in surface-accessible residues. As ankyrin repeats are protein
      interaction modules, these mutations may disrupt protein-protein interactions. A
      plausible scenario is that information exchange between the ankyrin and
      transmembrane domains is involved in activating defense signaling.

PMID- 16297073
TI  - Salinity stress adaptation competence in the extremophile Thellungiella halophila
      in comparison with its relative Arabidopsis thaliana.
AB  - In stark contrast to Arabidopsis, a related species, Thellungiella halophila
      (Thellungiella salsuginea; salt cress), displays extreme tolerance to high
      salinity, low humidity and freezing. High nucleotide sequence identity permits
      the use of tools developed for Arabidopsis for Thellungiella transcript
      profiling, for which a microarray platform with >25,000 DNA elements (70-mer
      oligonucleotides) was used. Microarray transcript profiling and intensity
      analysis, quantitative RT-PCR, and metabolite profiles define genes and pathways
      that showed shared and divergent responses to salinity stress in the two species.
      Shared responses are exemplified by 40% of the regulated genes functioning in
      confining ribosomal functions, photosynthesis and cell growth, as well as
      activating osmolyte production, transport activities and abscisic acid-dependent
      pathways. An additional 60% of regulated genes distinguished Thellungiella from
      Arabidopsis. Analysis of the differences showed that Arabidopsis exhibited a
      global defense strategy that required bulk protein synthesis, while Thellungiella
      induced genes functioning in protein folding, post-translational modification and
      protein redistribution. At 150 mm NaCl, Thellungiella maintained unimpeded
      growth. Transcript intensity analyses and metabolite profiles supported the
      microarray results, pointing towards a stress-anticipatory preparedness in
      Thellungiella.

PMID- 16297072
TI  - A pathogen-inducible patatin-like lipid acyl hydrolase facilitates fungal and
      bacterial host colonization in Arabidopsis.
AB  - Genes and proteins related to patatin, the major storage protein of potato
      tubers, have been identified in many plant species and shown to be induced by a
      variety of environmental stresses. The Arabidopsis patatin-like gene family
      (PLPs) comprises nine members, two of which (PLP2 and PLP7) are strongly induced
      in leaves challenged with fungal and bacterial pathogens. Here we show that
      accumulation of PLP2 protein in response to Botrytis cinerea or Pseudomonas
      syringae pv. tomato (avrRpt2) is dependent on jasmonic acid and ethylene
      signaling, but is not dependent on salicylic acid. Expression of a PLP2-green
      fluorescent protein (GFP) fusion protein and analysis of recombinant PLP2
      indicates that PLP2 encodes a cytoplasmic lipid acyl hydrolase with wide
      substrate specificity. Transgenic plants with altered levels of PLP2 protein were
      generated and assayed for pathogen resistance. Plants silenced for PLP2
      expression displayed enhanced resistance to B. cinerea, whereas plants
      overexpressing PLP2 were much more sensitive to this necrotrophic fungus. We also
      established a positive correlation between the level of PLP2 expression in
      transgenic plants and cell death or damage in response to paraquat treatment or
      infection by avirulent P. syringae. Interestingly, repression of PLP2 expression
      increased resistance to avirulent bacteria, while PLP2-overexpressing plants
      multiplied avirulent bacteria close to the titers reached by virulent bacteria.
      Collectively, the data indicate that PLP2-encoded lipolytic activity can be
      exploited by pathogens with different lifestyles to facilitate host colonization.
      In particular PLP2 potentiates plant cell death inflicted by Botrytis and reduces
      the efficiency of the hypersensitive response in restricting the multiplication
      of avirulent bacteria. Both effects are possibly mediated by providing fatty acid
      precursors of bioactive oxylipins.

PMID- 16297074
TI  - Transgenic proteoid roots of white lupin: a vehicle for characterizing and
      silencing root genes involved in adaptation to P stress.
AB  - White lupin (Lupinus albus L.) has become an illuminating model for the study of
      plant adaptation to phosphorus (P) deficiency. It adapts to -P stress with a
      highly coordinated modification of root development and biochemistry resulting in
      short, densely clustered secondary roots called proteoid (or cluster) roots. In
      order to characterize genes involved in proteoid root formation and function in a
      homologous system, we have developed an Agrobacterium rhizogenes-based
      transformation system for white lupin roots that allows rapid analysis of
      reporter genes as well as RNA interference (RNA(i))-based gene silencing. We used
      this system to characterize a lupin multidrug and toxin efflux (Lupinus albus
      MULTIDRUG AND TOXIN EFFLUX, LaMATE) gene previously shown to have enhanced
      expression under -P stress. Here, we show that LaMATE had high expression in
      proteoid roots not only under -P, but also under -Fe, -N, -Mn and +Al stress. A
      portion containing the putative LaMATE promoter was fused to GUS and enhanced
      green fluorescence protein (EGFP) reporter genes, and a translational
      LaMATE::EGFP fusion was constructed under control of the LaMATE promoter. The
      LaMATE promoter directed P-dependent GUS and EGFP expression to proteoid roots.
      Confocal microscopy in white lupin and Arabidopsis point to the plasma membrane
      as the likely location of the LaMATE protein. LaMATE displayed homology to FRD3
      in Arabidopsis, but did not complement an Arabidopsis ferric reductase defective
      3 (FRD3) mutant. RNA(i)-based gene silencing was shown to effectively reduce
      LaMATE expression in transformed white lupin roots. LaMATE RNAi-silenced plants
      displayed an about 20% reduction in dry weight.

PMID- 16297075
TI  - Reviewing models of auxin canalization in the context of leaf vein pattern
      formation in Arabidopsis.
AB  - In both plants and animals vein networks play an essential role in transporting
      nutrients. In plants veins may also provide mechanical support. The mechanism by
      which vein patterns are formed in a developing leaf remains largely unresolved.
      According to the canalization hypothesis, a signal inducing vein differentiation
      is transported in a polar manner and is channeled into narrow strands. Since
      inhibition of auxin transport affects venation patterns, auxin is likely to be
      part of the signal involved. However, it is not clear whether the canalization
      hypothesis, initially formulated over 25 years ago, is compatible with recent
      experimental data. In this paper we focus on three aspects of this question, and
      show that: (i) canalization models can account for an acropetal development of
      the midvein if vein formation is sink-driven; (ii) canalization models are in
      agreement with venation patterns resulting from inhibited auxin transport and
      (iii) loops and discontinuous venation patterns can be obtained assuming proper
      spacing of discrete auxin sources.

PMID- 16297076
TI  - Requirement of aminoacyl-tRNA synthetases for gametogenesis and embryo
      development in Arabidopsis.
AB  - Aminoacyl-tRNA synthetases (AARSs) are required for translation in three
      different compartments of the plant cell: chloroplasts, mitochondria and the
      cytosol. Elimination of this basal function should result in lethality early in
      development. Phenotypes of individual mutants may vary considerably, depending on
      patterns of gene expression, functional redundancy, allele strength and protein
      localization. We describe here a reverse genetic screen of 50 insertion mutants
      disrupted in 21 of the 45 predicted AARSs in Arabidopsis. Our initial goal was to
      find additional EMB genes with a loss-of-function phenotype in the seed. Several
      different classes of knockouts were discovered, with defects in both
      gametogenesis and seed development. Three major trends were observed. Disruption
      of translation in chloroplasts often results in seed abortion at the transition
      stage of embryogenesis with minimal effects on gametophytes. Disruption of
      translation in mitochondria often results in ovule abortion before and
      immediately after fertilization. This early phenotype was frequently missed in
      prior screens for embryo-defective mutants. Knockout alleles of non-redundant
      cytosolic AARSs were in general not identified, consistent with the absolute
      requirement of cytosolic translation for development of male and female
      gametophytes. These results provide a framework for evaluating redundant
      functions of AARSs in Arabidopsis, a valuable data set of phenotypes resulting
      from multiple disruptions of a single basal process, and insights into which
      genes are required for both gametogenesis and embryo development and might
      therefore escape detection in screens for embryo-defective mutants.

PMID- 16297077
TI  - Efficient insertional mutagenesis in rice using the maize En/Spm elements.
AB  - We have developed a novel system for insertional mutagenesis in rice (Oryza
      sativa) based on the maize (Zea mays) enhancer/suppressor mutator (En/Spm)
      element. In this system, a single T-DNA construct with Spm-transposase and the
      non-autonomous defective suppressor mutator (dSpm) element is used in conjunction
      with green fluorescent protein (GFP) and Discosoma sp. Red Fluorescence Protein
      (DsRed) fluorescent markers to select unlinked stable transpositions of dSpm.
      Using this system, we could demonstrate high frequencies of unlinked germinal
      transposition of dSpm in rice. Analysis of dSpm flanking sequences from 353
      stable insertion lines revealed that the dSpm insertions appear to be widely
      distributed on rice chromosomes with a preference for genic regions (70%). The
      dSpm insertions appear to differ from Activator-Dissociation (Ac-Ds) elements in
      genomic distribution and exhibit a greater fraction of unlinked transpositions
      when compared with Ds elements. The results obtained in this study demonstrate
      that the maize En/Spm element can be used as an effective tool for functional
      genomics in rice and can complement efforts using other insertional mutagens.
      Further, the efficacy of the non-invasive fluorescence-based selection system is
      promising for its application to other crops.

PMID- 16297078
TI  - Histochemical staining and quantification of plant mitochondrial respiratory
      chain complexes using blue-native polyacrylamide gel electrophoresis.
AB  - Our knowledge of the respiratory chain and associated defects depends on the
      study of the multisubunit protein complexes in the inner mitochondrial membrane.
      Functional analysis of the plant mitochondrial respiratory chain has been
      successfully achieved by a combination of blue-native polyacrylamide gel
      electrophoresis (BN-PAGE) for separation of the protein complexes, and in-gel
      histochemical staining of the enzyme activities. We have optimized this powerful
      technique by determining linear ranges of amount of protein and enzyme activity
      for each respiratory complex. Time courses of the in-gel enzyme activities were
      also performed to determine optimal reaction times. Using the in-gel activity
      staining method we have previously shown decreased activity of complex V
      (F(1)F(0)-ATPase) in male-sterile sunflowers (Sabar et al., 2003). Here we have
      identified unique supercomplexes comprising complex IV (cytochrome c oxidase) in
      sunflower mitochondria. This method therefore represents a reliable tool for the
      diagnosis of respiratory dysfunction. In addition, the wider application of BN
      PAGE in combination with enzyme activity staining is discussed.

PMID- 16297079
TI  - The use of breast magnetic resonance imaging in ductal carcinoma in situ.

PMID- 16297080
TI  - Determination of the presence and extent of pure ductal carcinoma in situ by
      mammography and magnetic resonance imaging.
AB  - The purpose of this study was to compare the ability of magnetic resonance
      imaging (MRI) and mammography to determine the presence and extent of ductal
      carcinoma in situ (DCIS). Retrospective review of medical records of women who
      underwent MRI and mammographic examination during a 23-month period revealed 39
      sites of pure DCIS in 33 breasts of 32 women. No invasive or microinvasive tumor
      was found. Women ranged in age from 34 to 79 years (mean age 53 years). In these
      33 breasts, both MRI and mammography were done before surgery. Reports and images
      of mammography and MRI were reviewed to determine if each study was positive for
      the presence of single or multiple sites of DCIS and the imaging patterns
      associated with these sites. Of 33 breasts involved, DCIS was discovered by MRI
      alone in 21 (64%), by both MRI and mammography in 8 (24%), and by mammography
      alone in 1 (3%); in 3 breasts (9%), DCIS was found at mastectomy without findings
      on mammography or MRI. MRI had significantly higher sensitivity than mammography
      for DCIS detection (29/33=88% versus 9/33=27%, p<0.00001). Multiple sites of
      disease were present in five breasts; these were better demonstrated with MRI in
      three, mammography in one, and equally by both in one. The predominant
      enhancement pattern of DCIS on MRI was linear/ductal in 18 of 29 breasts (62%);
      mammography found calcifications associated with DCIS in 8 of 9 (89%). The
      nuclear grade of DCIS found with MRI and mammography was similar; size of lesions
      was larger on MRI; breast density did not impact results. In this study, MRI was
      significantly more sensitive than mammography in DCIS detection. In women with
      known or suspected DCIS, MRI may have an important role to play in assessing the
      extent of disease in the breast.

PMID- 16297081
TI  - Evaluation of the benefit of using blue dye in addition to radioisotope for
      sentinel lymph node biopsy in patients with breast cancer.
AB  - The techniques for performing sentinel lymph node biopsy (SLNB) vary from
      institution to institution. Some advocate blue dye only, others radioisotope
      only, and many utilize a combination of both. The purpose of this study is to
      evaluate the additional benefit that blue dye provides when used in combination
      with a radioisotope. From October 2001 to June 2004, 102 SLNBs were attempted in
      99 patients with breast cancer using a combination of blue dye and radioisotope.
      A lymph node was considered a sentinel lymph node (SLN) when it was stained with
      blue dye, had a blue lymphatic afferent, or had increased radioactivity. Ninety
      eight patients had 101 successful identifications of SLNs, for an identification
      rate of 99%. Twenty-eight patients had positive SLNs. In three of those patients,
      although there were SLNs identified by both techniques, the positive SLNs were
      identified with only blue dye. Of the 102 SLNB procedures, there were two
      patients whose only SLN was identified by blue dye only. Although blue dye did
      not improve the identification rate, there was a definite benefit in improving
      the false-negative rate.

PMID- 16297082
TI  - Sentinel lymph node biopsy for ductal carcinoma in situ: an evolving approach at
      the University of Florida.
AB  - While sentinel lymph node biopsy (SLNB) has virtually replaced axillary
      dissection as the initial diagnostic procedure for invasive breast cancer, the
      role of SLNB in ductal carcinoma in situ (DCIS) remains controversial. The
      purpose of this study was to review our experience with SLNB in DCIS. All
      patients with DCIS or DCIS with microinvasion (DCISM) who underwent SLNB from
      June 1997 to April 2002 at the University of Florida were included for analysis.
      The indications for SLNB were at the discretion of the treating surgeon.
      Lymphatic mapping involved a sequential dermal-peritumoral radiocolloid injection
      and dynamic lymphoscintigraphy followed by an intraoperative assessment of
      radioactivity with a handheld gamma probe. All sentinel lymph nodes (SLNs) with
      radioactive counts>or=10% of the ex vivo counts of the most radioactive SLN were
      removed. Pathologic analysis consisted of slicing the SLN at 2 mm intervals for
      permanent section. All paraffin blocks of the SLNs were step sectioned in 4
      microm sections (92 microm spacing) through the entire lymph node. Slides were
      then stained with an immunohistochemical stain for cytokeratin (AE1/AE3) and
      evaluated by microscopy. Nodal metastases were classified using the 6th edition
      of the American Joint Committee on Cancer (AJCC) staging manual. From April 1998
      to April 2002, 43 patients with DCIS underwent SLNB at the University of Florida.
      Seven patients (16%) with multifocal or extensive DCIS (five patients) or DCISM
      (two patients) who underwent SLNB had a positive sentinel node. Two of the three
      patients considered positive by immunohistochemistry alone had either DCISM or
      invasive disease. Four (80%) of the five patients with extensive DCIS and a
      positive sentinel node were ultimately determined to have invasive or
      microinvasive disease. While SLNB remains controversial in DCIS, our data suggest
      that patients with extensive DCIS should undergo SLNB at the initial procedure to
      avoid the need for a second operation. Data from clinical trials are needed to
      determine the impact of SLNB results on overall survival in patients with DCIS.

PMID- 16297083
TI  - An audit of pain/discomfort experienced during image-guided breast biopsy
      procedures.
AB  - A prospective audit of 221 breast biopsies was carried out to assess the
      pain/discomfort experienced during image-guided breast biopsies. The only
      significant factor in pain scores was the size of the needle used. Fine-needle
      aspiration cytology using a 21-gauge needle was found to cause the most
      discomfort.

PMID- 16297084
TI  - Image-guided tissue sampling: where radiology meets pathology.
AB  - Image-guided breast tissue sampling has become an acceptable alternative to open
      surgical biopsy for nonpalpable lesions. Advantages of minimally invasive core
      biopsy compared to open surgical biopsy include lower cost, lower complication
      rates, and less cosmetic deformity for patients. However, false-negative core
      biopsies can occur. Thus the imaging of a breast lesion and the histologic result
      of the core biopsy must be carefully correlated. This involves communication
      between radiology and pathology.

PMID- 16297085
TI  - Hormone replacement therapy and breast cancer risk in California.
AB  - Numerous studies have documented increased breast cancer risks with hormone
      replacement therapy (HRT), but these do not give a woman her specific absolute
      risk for the remainder of her life. This article estimates the magnitude of the
      effect of HRT on breast cancer incidence in California and calculates a woman's
      cumulative risk of breast cancer with different formulations and durations of HRT
      use. The effects of HRT on the underlying breast cancer incidence were estimated
      using the attributable fraction method, applying HRT prevalence data from the
      2001 California Health Interview Survey and published rates of higher relative
      risk (RR) from HRT use from the Women's Health Initiative (WHI) study and Million
      Women's Survey (MWS). The annual number of breast cancers potentially
      attributable to HRT in California was estimated, along with individual cumulative
      risk of breast cancer for various ages to 79 years according to HRT use,
      duration, and formulation. Using the WHI data, 829 of 19,000 breast cancers
      (4.3%) in California may be attributable to HRT. This figure increases to 3401
      (17.4%) when the MWS RRs are applied. Use of estrogen-only HRT or short-term
      (approximately 5 years) use of combined HRT has a minimal effect on the
      cumulative risk calculated to the age of 79 years; application of the MWS data to
      a Californian woman commencing HRT at the age of 50 years (no HRT, 8.5%; estrogen
      only, 8.6%; combined, 9.1%). Prolonged (approximately 10 years) use of combined
      HRT increases the cumulative risk to 10.3%. This article demonstrates that HRT
      will generate a small additional risk of breast cancer in an individual. The
      reduction in perimenopausal symptoms may be considered sufficient to warrant this
      extra risk. However, this view needs to be balanced because the small increases
      in individual risk will be magnified, producing a noticeable change in population
      cancer caseload where HRT use is high.

PMID- 16297086
TI  - The role of ovarian ablation in the management of breast cancer.
AB  - In recent years the role of ovarian ablation as a therapeutic modality not only
      in the prevention but also in the treatment of breast cancer has reemerged after
      its initial use more than a century ago. BRCA-1 and BRCA-2 mutation carriers have
      an 85% lifetime risk of developing breast cancer. Bilateral salpingo-oophorectomy
      is effective in reducing the risk of developing breast cancer in both BRCA-1 and
      BRCA-2 mutation carriers by 50%. Tamoxifen reduces the risk of breast cancer in
      BRCA-2 mutation carriers, but not in BRCA-1 mutation carriers. Breast cancer
      arising in BRCA-1 mutation carriers is often estrogen receptor (ER) negative,
      unlike breast cancer developing in BRCA-2 mutation carriers. Sixty percent of
      premenopausal patients with breast cancer have ER-positive disease and 25% of
      breast cancer patients are premenopausal at diagnosis. The Early Breast Cancer
      Trialists' Collaborative Group review has shown ovarian ablation to be an
      effective adjuvant therapy for premenopausal breast cancer patients less than 50
      years of age. But the Early Breast Cancer Trialists' overview also shows the
      benefit of ovarian ablation is uncertain if these patients also receive
      chemotherapy. Does the overview underestimate the efficacy of ovarian ablation?
      Some patients in these trials were ER negative. Most women less than 50 years of
      age who receive adjuvant chemotherapy become menopausal. So there is a need to
      test ovarian function suppression in the group who can benefit, or in other
      words, those that remain premenopausal after chemotherapy and have endocrine
      responsive breast cancer.

PMID- 16297087
TI  - Quality of life in Brazilian breast cancer survivors age 45-65 years: associated
      factors.
AB  - The objectives of this study were to evaluate quality of life (QOL) and identify
      its associated factors in climacteric women with a history of breast cancer. A
      cross-sectional study was performed including 75 breast cancer survivors age 45
      65 years who had undergone complete oncologic treatment and nonusers of hormone
      therapy or tamoxifen in the last 6 months. Sociodemographic and clinical
      characteristics in addition to the prevalence of climacteric symptoms were
      evaluated. QOL was evaluated by the Medical Outcomes Study 36-item Short-Form
      Health Survey (SF-36) questionnaire, including eight components that can be
      condensed into two summaries: a physical component summary (physical functioning,
      role-physical, body pain, general health) and a mental component summary
      (vitality, social functioning, role-emotional, and mental health). Generalized
      linear models were used to analyze the data, allowing the identification of
      factors affecting QOL, adjusting for confounding variables. The mean age of the
      participants was 53.1+/-5.9 years. Breast cancer survivors reported good QOL. The
      most prevalent symptoms were nervousness (69%) and hot flashes (56%). Factors
      associated with poorer QOL were dizziness, postmenopausal status, and breast
      conserving therapy (physical component), as well as insomnia and being married
      (mental component). In conclusion, participants demonstrated good QOL. We
      identified factors that may influence QOL in women with breast cancer,
      highlighting being married, climacteric symptoms, postmenopausal status, and
      breast-conserving therapy. Given the impact of these factors, health
      professionals and patients must discuss choices for alleviating climacteric
      symptoms and explanations for the potential repercussions of breast cancer
      treatment.

PMID- 16297088
TI  - Histopathologic characteristics predicting HER-2/neu amplification in breast
      cancer.
AB  - The HER-2/neu gene is a proto-oncogene that is amplified in 10-30% of breast
      cancers. New drugs for targeted therapy, such as Herceptin, are effective for
      patients with HER-2/neu-positive tumors, making it necessary to have a noncostly
      and accurate method to assess HER-2/neu status. We studied the correlation of
      findings made by fluorescent in situ hybridization (FISH) and
      immunohistochemistry (IHC) staining and the possibility of combining IHC and
      other clinicopathologic characteristics of breast tumors to predict FISH
      determined HER-2/neu status. The clinicopathologic characteristics analyzed were
      the size of the tumor, p53, lymph-vascular invasion, estrogen/progesterone
      receptors (ER/PR), tumor grade, axillary lymph node status, and patient age. A
      total of 199 cases of invasive breast cancer studied at the UCLA Pathology
      Laboratory during 2003 were included in this study. Tumors with IHC 0, 1+, 2+,
      and 3+ scores were found to be FISH positive in 3.5%, 6.4%, 25.7%, and 81.5% of
      the respective groups. Our study showed a strong association between the FISH
      negative and IHC scored 0 and 1+ tumors, suggesting that the FISH test may not be
      necessary in these cases (p<0.0001). Although the concordance between IHC 3+ and
      FISH positive is high, 18% of the patients with overexpression of HER-2/neu fail
      to show gene amplification by FISH. HER-2/neu positivity was found to be
      proportionally associated with increasing grade in infiltrating ductal carcinoma
      (p<0.0001). p53-positive tumors are more likely to be HER-2/neu amplified
      (p=0.0003). Tumors that are negative for ER/PR are also associated with HER-2/neu
      positivity by FISH (31.15%, p=0.0016). FISH-determined HER-2/neu status is not
      associated with histologic type, tumor size, nodal status, lymph-vascular
      invasion, or patient age.

PMID- 16297089
TI  - Study of sexual functioning determinants in breast cancer survivors.
AB  - Our goal was to identify the treatment, personal, interpersonal, and hormonal
      (testosterone) factors in breast cancer survivors (BCSs) that determine sexual
      dysfunction. The treatment variables studied were type of surgery, chemotherapy,
      radiation, and tamoxifen. The personal, interpersonal, and physiologic factors
      were depression, body image, age, relationship distress, and testosterone levels.
      A sample of 55 female breast cancer survivors seen for routine follow-up
      appointments from July 2002 to September 2002 were recruited to complete the
      Female Sexual Functioning Index (FSFI), Hamilton Depression Inventory (HDI), Body
      Image Survey (BIS), Marital Satisfaction Inventory-Revised (MSI-R), a demographic
      questionnaire, and have a serum testosterone level drawn. The average time since
      diagnosis was 4.4 years (SD 3.4 years). No associations were found between the
      type of cancer treatment, hormonal levels, and sexual functioning. BCS sexual
      functioning was significantly poorer than published normal controls in all areas
      but desire. The BCSs' level of relationship distress was the most significant
      variable affecting arousal, orgasm, lubrication, satisfaction, and sexual pain.
      Depression and having traditional role preferences were the most important
      determinants of lower sexual desire. BCSs on antidepressants had higher levels of
      arousal and orgasm dysfunction. Women who were older had significantly more
      concerns about vaginal lubrication and pain. Relationship concerns, depression,
      and age are important influences in the development of BCS sexual dysfunction.
      The relationship of testosterone and sexual dysfunction needs further study with
      larger samples and more accurate assay techniques.

PMID- 16297090
TI  - Numerical aberrations of chromosomes 1 and 7 by fluorescent in situ hybridization
      and DNA ploidy analysis in breast cancer.
AB  - The goals of this study were to detect the numerical alterations of chromosomes 1
      and 7 in breast cancer and to correlate the findings with DNA ploidy status as
      well as with parameters of prognostic significance. Fluorescence in situ
      hybridization (FISH) with centromeric probes for chromosomes 1 and 7 and cellular
      DNA content measurement by image analysis-based cytophotometry were applied on
      interface nuclei from fresh tissue imprints of 59 breast ductal carcinomas.
      Immunohistochemical stainings for estrogen receptor (ER), progesterone receptor
      (PR), HER-2, p53, and Ki67 were performed on paraffin tumor sections. The
      correlation between DNA ploidy and chromosomal aberrations revealed a significant
      association between aneuploidy and aneusomy for both chromosomes 1 (p=0.002) and
      7 (p=0.00001), however, a number of diploid tumors were found to be aneusomic,
      especially for chromosome 1. Chromosome 7 polysomy was significantly associated
      with a higher incidence of axillary lymph node metastasis (p=0.05), poorly
      differentiated (grade III) tumors (p=0.03), negative ER and PR status (p=0.02 and
      0.001, respectively), as well as p53 protein expression (p=0.05) and a higher
      Ki67 labeling index (p=0.004). Chromosome 1 aneusomy was only related with HER-2
      protein overexpression (p=0.05). No association between chromosome alterations
      and tumor size was detected. In conclusion, the results of our study indicate
      that the detection of numerical aberrations of chromosomes 1 and 7 by FISH seems
      to be more sensitive than DNA ploidy status for the evaluation of abnormal
      cellular DNA and chromosome 7 aneusomy characterizes tumors with aggressive
      features and therefore might be a useful predictor of unfavorable biological
      behavior in breast cancer.

PMID- 16297092
TI  - The distinctive role of positron emission tomography/computed tomography in
      breast carcinoma with brown adipose tissue 2-fluoro-2-deoxy-d-glucose uptake.
AB  - The diagnostic power of an integrated positron emission tomography/computed
      tomography (PET/CT) system for whole-body 2-fluoro-2-deoxy-d-glucose (FDG)
      imaging is clearly demonstrated in this case report. The precise anatomic
      localization of FDG uptake with CT in a PET/CT scan of a patient with known
      breast carcinoma helped identify a contralateral breast tumor with axillary lymph
      node metastasis despite the presence of extensive physiologic brown fat FDG
      uptake. Accordingly, the patient received appropriate surgical management and
      pathologic confirmation of the disease.

PMID- 16297091
TI  - The role of conservative treatment in idiopathic granulomatous mastitis.
AB  - Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory disease of
      the breast that mimics carcinoma of the breast. Its etiology and treatment remain
      unclear. A retrospective review of nine women with histopathologic diagnosis of
      IGM was performed. The women had a mean follow-up of 18.7 months and a mean age
      of 45.7 years (range 32-83 years). The main presentation was breast mass (100%).
      Clinically and radiologically, 55.6% of the women were suspected to have
      malignancy. One patient was treated with lumpectomy without recurrence. Eight
      patients were treated with expectant management with close regular surveillance.
      No surgery was performed and no medications were given. Fifty percent of the
      patients had spontaneous complete resolution of disease after a mean interval of
      14.5 months. These four patients had no recurrence. Fifty percent of patients had
      static disease. In conclusion, it is important to differentiate IGM from
      carcinoma of the breast. Tissue biopsy remains the gold standard to confirm the
      diagnosis. Expectant management with close regular surveillance is the treatment
      of choice.

PMID- 16297093
TI  - Erdheim-Chester disease of the breast: a case report and review of the
      literature.
AB  - Erdheim-Chester disease (ECD) is a rare xanthomatous non-Langerhans cell
      histiocytosis which involves the marrow space of the long bones. Extraosseous
      sites most commonly affected include the eyes, lungs, pituitary glands, and
      kidneys. We report the case of a 49-year-old woman who presented with palpable
      breast nodules, followed by progressive soft tissue and subcutaneous disease, and
      involvement of the long bones, dysarthria, and dysphagia. The histopathologic
      features and skeletal radiography findings are consistent with ECD. This case
      represents an unusual presentation, which led to delayed diagnosis, as ECD of the
      breast has been rarely reported. ECD should be considered in the differential
      diagnosis of histiocytoid breast lesions, including fat necrosis and histiocytoid
      invasive mammary carcinoma.

PMID- 16297094
TI  - Blue hives localized to the opposite arm after patent blue v injection for lymph
      node mapping in breast cancer.

PMID- 16297096
TI  - Papillary intraductal carcinoma with extensive secretory endometrium-like
      subnuclear vacuolization.

PMID- 16297095
TI  - Lymphocutaneous nocardiosis in a lymphopenic breast cancer patient under
      treatment with docetaxel.

PMID- 16297097
TI  - Pseudoangiomatous hyperplasia of mammary stroma in a male breast presenting as a
      discrete nodule.

PMID- 16297099
TI  - Eyelid swelling: an unusual presentation of metastatic lobular carcinoma of the
      breast.

PMID- 16297098
TI  - Vacuum-assisted breast biopsy device (mammotome) malfunction simulating
      microcalcifications.

PMID- 16297100
TI  - Spontaneous resolving breast microcalcifications associated with breast
      carcinoma.

PMID- 16297101
TI  - Small bowel obstruction: an unusual presentation of metastatic breast carcinoma.

PMID- 16297102
TI  - Cystic-appearing pleural metastasis in a patient with recurrent phyllodes tumor.

PMID- 16297103
TI  - Metastasis to the male breast from hypopharyngeal squamous cell carcinoma.

PMID- 16297104
TI  - Radiation therapy as a trigger factor for initially localized bullous pemphigoid.

PMID- 16297105
TI  - Primary alveolar-type large cell neuroendocrine carcinoma of the breast.

PMID- 16297106
TI  - Biclonal breast carcinoma metastatic to a supraclavicular lymph node.

PMID- 16297107
TI  - Schistosomiasis presenting with microcalcifications on mammography.

PMID- 16297108
TI  - Ductal breast carcinoma presenting with methicillin-resistant Staphylococcus
      aureus mastitis.

PMID- 16297109
TI  - Magnetic resonance imaging findings in an axillary accessory breast fibroadenoma.

PMID- 16297110
TI  - Primary breast lymphoma: radiologic and pathologic findings.

PMID- 16297111
TI  - A solitary metastasis of breast cancer to the urinary bladder.

PMID- 16297112
TI  - Breast hemangioma simulating an inflammatory carcinoma.

PMID- 16297113
TI  - Galactorrhea after conservative surgery for breast cancer.

PMID- 16297114
TI  - Cutaneous subareolar leiomyoma: a rare clinical entity.

PMID- 16297115
TI  - Metastases to the breast from primary pancreatic cancer.

PMID- 16297116
TI  - Breast biopsy marker masquerading as a mass lesion.

PMID- 16297117
TI  - Diagnosis of recurrent breast cancer by ductoscopy.

PMID- 16297118
TI  - Calcifications of the breast in Onchocerca infection.

PMID- 16297119
TI  - Lobular carcinoma located in a breast hamartoma.

PMID- 16297120
TI  - Intraluminal crystalloids in benign breast ducts.

PMID- 16297121
TI  - Cavernous hemangioma of the male breast.

PMID- 16297122
TI  - Pleomorphic adenoma of the breast.

PMID- 16297123
TI  - Cystic lymphangioma of the breast.

PMID- 16297124
TI  - Primary angiosarcoma of the breast.

PMID- 16297126
TI  - Massive benign phyllodes tumor.

PMID- 16297125
TI  - Granular cell tumor of the breast.

PMID- 16297127
TI  - Liesegang rings.

PMID- 16297128
TI  - A case of premenopausal breast cancer showing remarkable elevation of serum
      alkaline phosphatase level during treatment with LH-RH analog.

PMID- 16297130
TI  - Breast cancer risk communication: modalities and effectiveness.

PMID- 16297129
TI  - Breast abscess: a unique presentation as primary septic arthritis of the
      sternoclavicular joint.

PMID- 16297131
TI  - Myasthenia gravis in a patient with breast cancer.

PMID- 16297133
TI  - Interphase cytogenetics of male breast cancer.

PMID- 16297132
TI  - Axillary web syndrome: practical implications.

PMID- 16297134
TI  - Differential diagnosis of granulomatous mastitis.

PMID- 16297136
TI  - Eosinophilic oesophagitis and pollen.

PMID- 16297137
TI  - Eosinophil infiltration of the oesophageal mucosa in patients with pollen allergy
      during the season.
AB  - BACKGROUND: The oesophagus is normally devoid of eosinophils. There are some
      disorders accompanying with eosinophil infiltration. Food allergy has been
      reported as a common reason, especially in children but some other studies have
      also indicated that aeroallergens might have a role in oesophageal eosinophil
      accumulation. OBJECTIVE: In this study we investigated whether there is any
      eosinophil recruitment in the oesophagus of pollen-allergic patients who had
      respiratory symptoms during the season. METHODS: Thirty-eight symptomatic
      patients (allergic rhinitis (AR) with or without asthma) who had sensitization to
      grass pollen were included in the study during the pollen season. Controls were
      composed of 25 healthy non-atopics and 24 patients diagnosed as having gastro
      oesophageal reflux disease. Reflux was excluded in allergic and non-atopic
      groups, whereas the presence of allergy was eliminated in control groups.
      Gastrointestinal endoscopy was performed in all participants, and biopsy
      specimens were taken from both the proximal and the distal oesophagus to evaluate
      eosinophil accumulation. At the same time, blood eosinophil numbers were counted.
      Results Oesophageal eosinophil accumulation was found in 10 allergic patients
      (26%) and in five patients (21%) with gastro-oesophageal reflux disease but none
      of the healthy controls had eosinophils (0%) (P<0.05). Blood eosinophils were
      higher in these 10 patients than the rest of the 28 patients without
      infiltration. In this group, blood eosinophils were also correlated with the
      number of accumulated eosinophils in the oesophagus (P<0.001). There was more
      intense eosinophil infiltration at the distal part of the oesophagus in the
      reflux group when compared with the allergic group (mean 7.6+/-5.6 vs. 3.2+/
      3.7). Nevertheless, eosinophils were found to be concentrated (mean 5.5+/-7.3) in
      the proximal oesophagus of allergic patients, although it was 1.7+/-1.5 in reflux
      patients (P>0.05). Conclusion Our results showed that eosinophil infiltration
      might be observed in oesophageal tissue of patients with respiratory tract
      allergy during the symptomatic period. This finding may possibly reflect the
      systemic and common mucosal aspects of allergic inflammation.

PMID- 16297138
TI  - A case-control study of bronchial asthma associated with ulcerative colitis: role
      of airway microvascular permeability.
AB  - BACKGROUND: Recent attention has been devoted to the respiratory manifestations
      that may be associated with diseases of distant organs. The most prevalent and
      distinctive pattern of respiratory involvement in ulcerative colitis (UC) is
      airway inflammation. OBJECTIVE: This study was designed to examine the
      contribution of airway microvascular permeability to the pathophysiological
      association of asthma with UC. METHODS: Sputum induction and methacholine
      provocation test were performed in 27 asthmatic patients (15 without UC and 12
      with UC), nine patients with UC and 15 normal controls. Inflammatory indexes,
      vascular endothelial growth factor (VEGF) levels in induced sputum, airway
      vascular permeability index and exhaled nitric oxide (NO) levels were examined in
      all subjects. RESULTS: The percentage of eosinophils and concentration of
      eosinophil cationic protein in induced sputum were similar in all four groups.
      Though exhaled NO levels were significantly higher in asthmatics with or without
      UC than in normal controls or UC patients, these levels were comparable in
      asthmatics with and without UC. VEGF levels in induced sputum and airway vascular
      permeability index were significantly higher in asthmatics without UC (VEGF: 1920
      (990) pg/mL; airway vascular permeability index: 0.018 (0.008)) and asthmatics
      with UC (6570 (1000) pg/mL; 0.040 (0.006)) than in normal controls (950 (700)
      pg/mL; 0.009 (0.003)), whose levels were comparable to those of UC patients (900
      (600) pg/mL; 0.011 (0.003)). In particular, these parameters were markedly
      increased in asthmatics with UC than in asthmatics without UC. VEGF level was
      significantly correlated with airway vascular permeability index in asthmatics
      with UC. Moreover, VEGF level and airway vascular permeability index was
      inversely correlated with degree of airway obstruction and airway hyper
      reactivity to methacholine in these asthmatics. CONCLUSION: Airway microvascular
      hyper-permeability induced by VEGF may have a profound effect on airway function
      and can explain the heightened airway hyper-responsiveness characteristic of
      asthma associated with UC.

PMID- 16297139
TI  - Vascular endothelial growth factor up-regulation and bronchial wall remodelling
      in asthma.
AB  - BACKGROUND: There is increasing in vitro evidence to support a role for vascular
      endothelial growth factor (VEGF), a major regulator of angiogenesis, as a
      mediator of fibrosis associated with neovascularization. OBJECTIVE: We tested the
      hypothesis that VEGF is involved both in increased airway mucosal vascularity and
      in the subepithelial fibrosis of asthmatic patients. METHODS: Bronchial biopsies
      were performed in 24 asthmatic patients and eight healthy controls.
      Immunostaining, using computerized image analysis, was performed using monoclonal
      antibodies against VEGF(+) cells, type IV collagen, to outline the basement
      membrane thickness, and tryptase and EG2, to identify mast cells and eosinophils,
      respectively. RESULTS: The counts of VEGF(+) cells (P<0.05), mast cells and
      EG2(+) cells (both P<0.01) were higher in asthmatics than in controls. The number
      of vessels, the vascular area in the lamina propria, and the basement membrane
      thickness were significantly higher in asthmatics than in healthy volunteers
      (P<0.01). Moreover, in asthmatic patients, the number of VEGF(+) cells was
      significantly related to the number of vessels (P<0.01), to mast cells (P<0.01)
      and to basement membrane thickness (P<0.01). A colocalization study also revealed
      that mast cells were a relevant cellular source of VEGF. High doses of inhaled
      fluticasone propionate significantly reduced VEGF(+) cells (P<0.05), vessel
      number (P<0.05), vascular area (P<0.05) and basement membrane thickness (P<0.05)
      in a subgroup of asthmatic patients. CONCLUSIONS: This study shows that VEGF, in
      addition to being involved in the vascular component of airway remodelling, may
      play a role in the thickening of the basement membrane in asthma.

PMID- 16297140
TI  - Transcriptional up-regulation of histamine receptor-1 in epithelial, mucus and
      inflammatory cells in perennial allergic rhinitis.
AB  - BACKGROUND: Histamine receptors play an important role in the pathogenesis of
      nasal allergy. Activation of histamine receptor 1 (H1R) and 2 (H2R) can cause
      allergic symptoms which can be blocked effectively by antihistamines. H1R and H2R
      transcript levels have been found to be up-regulated in perennial - but not in
      seasonal - allergic rhinitis (AR). The present study aimed to explore H1R and H2R
      expression in complex tissues of the nasal mucosa of perennial allergic rhinitis
      (PAR). METHODS: Ten patients with PAR and 13 non-AR subjects were recruited for
      the study by medical history, physical examination and laboratory screening
      tests. In this study, we have analysed single cells dissected from the nasal
      mucosa biopsies by laser-assisted microdissection. H1R mRNA expression was
      analysed in different cell types such as epithelial, endothelial, mucus and
      inflammatory cells isolated from the nasal mucosa of PAR in comparison with non
      AR subjects. RESULTS: H1R mRNA gene expression level was significantly increased
      in the nasal mucosa of PAR in comparison with non-AR (P<0.0001). H1R mRNA was
      significantly elevated in epithelial (P<0.001) and mucus cells (P<0.05) of PAR in
      comparison with non-AR whereas H1R gene expression levels in endothelial cells
      between both groups were not changed (P=0.23). Interestingly, inflammatory cells
      in the nasal mucosa of PAR patients were also strongly expressed H1R mRNA
      (P<0.001). CONCLUSION: The present study indicates that PAR alters the expression
      of H1R mRNA in epithelial, mucus and inflammatory cells of the nasal mucosa and
      but not in endothelial cells. Therefore, epithelial, mucus and inflammatory cells
      may play an important role in histamine-mediated allergic airway inflammation in
      PAR.

PMID- 16297141
TI  - Wheezing in Chinese schoolchildren: disease severity distribution and management
      practices, a community-based study in Hong Kong and Guangzhou.
AB  - BACKGROUND: Asthma is a common chronic disease and information on its management
      practices at the community level is helpful in identifying problems and improving
      asthma care. OBJECTIVE: To assess the severity status and management of the
      asthma symptom of wheeze of children at the community level in Hong Kong (HK) and
      Guangzhou (GZ). METHODS: Cross-sectional study of children aged 10 years using
      the International Study of Asthma and Allergic disease in Childhood (ISAAC Phase
      II protocol). Asthma management and lung function were assessed in 178 (98 from
      HK and 80 from GZ) randomly selected children with wheeze over the past 12
      months. RESULTS: Eighty-three percent, 11%, 6% and 0% of children suffered from
      intermittent, mild persistent, moderate persistent and severe persistent asthma,
      respectively, according to the frequency of their symptoms. Addition of
      spirometric parameter only changed the asthma severity classification in 2.8% of
      children. Medications were used by 30.6% and 71.3% of children for wheeze in HK
      and GZ, respectively. In HK, inhaled beta(2)-agonist (73.3% among the drug users)
      was the commonest medication used followed by inhaled corticosteroid (ICS)
      (23.3%). In GZ, inhaled beta(2)-agonist was used by 75.4% of children, but use of
      ICS (26.3%), oral beta(2)-agonist (26.3%), oral theophylline (45.6%), oral
      ketotifen (36.8%) and oral steroid (35.1%) were also common. ICS was only used by
      11.4% of children with persistent asthma. Ten percent and 18.7% of children in HK
      and GZ, respectively, had emergency department visits, while 16.3% and 11.6% of
      children in HK and GZ, respectively, had missed school secondary to asthma over
      the past 1 year. CONCLUSIONS: Most children in the community had intermittent
      asthma and addition of lung function to symptoms did not significantly affect
      classification of asthma severity. Significant morbidity was seen even in this
      group of children with mostly intermittent and mild persistent asthma.

PMID- 16297142
TI  - Allergic rhinitis with or without concomitant asthma: difference in perception of
      dyspnoea and levels of fractional exhaled nitric oxide.
AB  - BACKGROUND/AIM: Allergic rhinitis (AR) is a risk factor for developing clinical
      asthma. Moreover, AR is often associated with bronchial hyper-responsiveness
      (BHR). The aim of the present study was to investigate whether patients with AR
      and asthma differed from AR with or without BHR in degree of perception of
      dyspnoea and airway inflammation, measured as fractionated exhaled nitric oxide
      (NO). MATERIALS: Twenty-nine patients with seasonal AR (timothy) were
      investigated with metacholine challenge test. Fourteen healthy non-reactive
      subjects served as controls. METHODS: (1) Metacholine challenge test, cut-off
      value forced expiratory volume in 1 s (FEV(1)) PD20 2,000 microg. Slope value for
      metacholine was calculated as %fall in FEV(1)/mol metacholine. Dyspnoea during
      challenge was measured with a 10-graded modified Borg score. (2) Measurement of
      fractional-exhaled nitric oxide (FENO) at flow rate 50 mL/s. RESULTS: Eighteen
      patients reported AR only, without asthma symptoms, and 12 (67%) were BHR. Eleven
      subjects had both rhinitis and asthma symptoms. Patients with rhinitis and asthma
      reported significantly more dyspnoea per percent fall in FEV(1) compared with
      those with rhinitis and BHR. Moreover, those with rhinitis and asthma had
      significantly higher NO values compared with those with rhinitis and BHR.
      CONCLUSION: The difference between rhinitis patients with or without asthma
      symptoms seems to be mainly a question of perception of dyspnoea. However, FENO
      measurement indicates that dyspnoea may also be associated with increased
      inflammatory activity in the peripheral airways.

PMID- 16297143
TI  - Markers of platelet activation in plasma of patients suffering from persistent
      allergic rhinitis with or without asthma symptoms.
AB  - BACKGROUND: Increased circulating levels of platelet release products are
      detected in various types of inflammation. It has been demonstrated that allergen
      challenge promotes platelet activation and leads to the release of chemokines
      such as platelet factor 4 (PF-4) and beta-thromboglobulin (beta-TG). OBJECTIVE:
      The aim of this study was to determine whether or not circulating platelets get
      into an activated state during allergic inflammatory reactions induced by long
      term natural exposure to allergens. METHODS: Plasma levels of PF-4 and beta-TG
      (established markers of in vivo platelet activation) were determined by ELISA
      method in symptomatic patients with allergy to house dust mites, suffering from
      persistent allergic rhinitis (PAR) in the absence of asthma symptoms (12 men and
      8 women; mean age 22 years) and from PAR with mild asthma (10 men and 6 women;
      mean age 23 years), as well as in healthy controls (10 men and 10 women; mean age
      23 years). RESULTS: No significant differences were found between PAR patients
      with or without symptoms of asthma and healthy non-atopic subjects with respect
      to plasma levels of PF-4 and beta-TG as well as platelet count. CONCLUSIONS: It
      seems that patients undergoing continuous natural exposure to sensitizing
      allergens, with subsequent PAR alone or with concomitant mild asthma, have no
      altered platelet activity in vivo, as reflected by plasma levels of the
      chemokines. These findings, in conjunction with earlier data, indicate that
      differences may exist in platelet activity, including releasability of platelet
      products between patients with distinct clinical manifestation of atopy.

PMID- 16297144
TI  - Caesarean section delivery and the risk of allergic disorders in childhood.
AB  - BACKGROUND: The composition of the intestinal flora in young children, if
      unfavourable, may increase the susceptibility to allergic disorders. Beneficial
      intestinal microbes originate from the maternal vaginal tract and thus are more
      likely to be transferred during vaginal births than during Caesarean sections (C
      sections). OBJECTIVE: To determine whether children born by C-section have a
      different risk of allergic disorders compared with those delivered vaginally. We
      also tested the hypothesis that the risk of allergic disorders is highest for
      children born after 'repeat C-sections'. METHODS: A retrospective cohort study of
      8,953 children aged 3-10 years. Children diagnosed with allergic
      rhinoconjunctivitis (AR), asthma, atopic dermatitis (AD), or food allergies were
      identified from the Kaiser Permanente Northwest Region electronic records. The
      children's sex, birth weight, birth order, postnatal exposure to antibiotics as
      well as the mothers' age, ethnicity, education, marital status, smoking status
      during pregnancy, and use of asthma or hayfever medications were identified
      through the mothers' medical records or through the Oregon Birth Registry.
      RESULTS: The risk of being diagnosed with AR was significantly higher in the
      children born by C-section than in those delivered vaginally: adjusted odds ratio
      (OR)=1.37%, 95% confidence interval (CI)=1.14-1.63. Delivery by C-section was
      also associated with the subsequent diagnosis of asthma (OR=1.24%, 95% CI=1.01
      1.53); this association was gender specific, with a positive association
      restricted to girls (OR for asthma in girls: OR=1.53%, 95% CI=1.11-2.10; in boys:
      OR=1.08%, 95% CI=0.81-1.43). There was no significant association between mode of
      delivery and AD. If children born in a 'repeat C-section' were considered
      separately the risk of being diagnosed with AR increased further (OR=1.78%, 95%
      CI=1.34-2.37). The same increase was noted for asthma in girls (OR=1.83%, 95%
      CI=1.13-2.97) but not in boys. CONCLUSION: Caesarean sections may be associated
      with an increased risk of developing AR in childhood.

PMID- 16297145
TI  - Patterns of food allergen-specific cytokine production by T lymphocytes of
      children with multiple allergies.
AB  - BACKGROUND: The contribution of different T cell subsets to the overall measured
      cytokine response to food allergens is largely unexplored. METHOD: The patterns
      of cytokine production of peripheral blood-derived T cells after allergen
      stimulation were studied in 22 children with multiple food allergies and in 20
      non-allergic children as controls, using flow cytometry. RESULTS: Proportions of
      T cells of food-sensitized children spontaneously secreting IFN-gamma and IL-10
      (without antigen stimulation) were lower than non-atopic children and adult
      controls (P<or=0.001). The proportions of IL-4-producing cells in vitro were
      significantly increased (P<or=0.04) and IFN-gamma-producing cells were
      significantly reduced (P<or=0.05) in sensitized children after incubation with
      and without dendritic cell presentation of peanut extract, beta-lactoglobulin and
      ovalbumin. The reverse pattern was found in non-sensitized children and adult
      controls. IL-4 secretion in allergic children to sensitizing allergens was mainly
      restricted to the CD4(+) CD45 RO(+) population while in non-atopic controls both
      CD4(+) and CD8(+) CD45 RO(+) cells produced mostly IFN-gamma. Food-specific IgE
      values did not correspond with cytokine responses but IL-4 production and IFN
      gamma reduction relative to normal children were closely associated with total
      IgE levels. CONCLUSION: Food-allergic children's IL-4 cytokine response to their
      relevant allergens is predominantly from a memory population of CD4(+) CD45 RO(+)
      cells, whereas IL-4 and IFN-gamma secretion of non-allergic controls was
      predominantly from mixed CD4(+) and CD8(+) CD45 RO(+) populations.

PMID- 16297146
TI  - Identification of strong interleukin-10 inducing lactic acid bacteria which down
      regulate T helper type 2 cytokines.
AB  - BACKGROUND: Decreased exposure to microbial stimuli has been proposed to be
      involved in the increased prevalence of atopic disease. Such a relationship was
      indicated by enhanced presence of typical probiotic bacteria in the intestinal
      flora correlating with reduced prevalence of atopic disease. Recent clinical
      trials suggested that probiotic bacteria may decrease and prevent allergic
      symptoms, but which (different) species or strains may contribute is poorly
      understood. OBJECTIVE: We sought to select probiotic bacteria by their ability to
      modulate in vitro production of cytokines by peripheral blood mononuclear cells
      (PBMCs), to make a rational choice from available strains. METHODS: PBMCs,
      purified monocytes, and lymphocytes from healthy donors were co-cultured with 13
      different strains of probiotic bacteria. The effect of lactic acid bacteria (LAB)
      on different cell populations and effects on cytokine production induced by the
      polyclonal T cell stimulator phytohaemagglutinin (PHA) was evaluated by measuring
      T helper type 1, T helper type 2 (Th2), and regulatory cell cytokines in culture
      supernatants by multiplex assay. RESULTS: PBMCs cultured with different strains
      produced large amounts of IL-10 and low levels of IL-12p70, IL-5, and IL-13. In
      PHA-stimulated PBMC cultures, the tested strains decreased the production of Th2
      cytokines. Neutralizing IL-10 production resulted in partial to full restoration
      of Th2 cytokine production and concurred with an increase in pro-inflammatory
      cytokines such as IL-12p70 and TNF-alpha. Within the PBMCs, the CD14(+) cell
      fraction was the main source of IL-10 production upon interaction with LAB.
      CONCLUSION: Our results indicate that certain strains of lactobacilli and
      bifidobacteria modulate the production of cytokines by monocytes and lymphocytes,
      and may divert the immune system in a regulatory or tolerant mode. These specific
      strains may be favorable to use in prevention or treatment of atopic disease.

PMID- 16297147
TI  - Molecular cloning and immunoglobulin E reactivity of a natural rubber latex
      lecithinase homologue, the major allergenic component of Hev b 4.
AB  - BACKGROUND: Hev b 4 is an allergenic natural rubber latex (NRL) protein complex
      that is reactive in skin prick tests and in vitro immunoassays. On SDS
      polyacrylamide gel electrophoresis (SDS-PAGE), Hev b 4 is discerned predominantly
      at 53-55 kDa together with a 57 kDa minor component previously identified as a
      cyanogenic glucosidase. Of the 13 NRL allergens recognized by the International
      Union of Immunological Societies, the 53-55 kDa Hev b 4 major protein is the only
      candidate that lacks complete cDNA and protein sequence information. OBJECTIVE:
      We sought to clone the transcript encoding the Hev b 4 major protein, and
      characterize the native protein and its recombinant form in relation to IgE
      binding. METHODS: The 5'/3' rapid amplification of cDNA ends method was employed
      to obtain the complete cDNA of the Hev b 4 major protein. A recombinant form of
      the protein was over-expressed in Escherichia coli. The native Hev b 4 major
      protein was deglycosylated by trifluoromethane sulphonic acid. Western
      immunoblots of the native, deglycosylated and recombinant proteins were performed
      using both polyclonal antibodies and sera from latex-allergic patients. RESULTS:
      The cDNA encoding the Hev b 4 major protein was cloned. Its open reading frame
      matched lecithinases in the conserved domain database and contained 10 predicted
      glycosylation sites. Detection of glycans on the Hev b 4 lecithinase homologue
      confirmed it to be a glycoprotein. The deglycosylated lecithinase homologue was
      discerned at 40 kDa on SDS-PAGE, this being comparable to the 38.53 kDa mass
      predicted by its cDNA. Deglycosylation of the lecithinase homologue resulted in
      the loss of IgE recognition, although reactivity to polyclonal rabbit anti-Hev b
      4 was retained. IgE from latex-allergic patients also failed to recognize the non
      glycosylated E. coli recombinant lecithinase homologue. CONCLUSION: The IgE
      epitopes of the Hev b 4 lecithinase homologue reside mainly in its carbohydrate
      moiety, which also account for the discrepancy between the observed molecular
      weight of the protein and the value calculated from its cDNA.

PMID- 16297148
TI  - Female mice are more susceptible to the development of allergic airway
      inflammation than male mice.
AB  - BACKGROUND: In humans the prevalence of asthma is higher among females than among
      males after puberty. The reason for this phenomenon is not clear. OBJECTIVE: We
      tested the hypothesis that female mice are more susceptible to the development of
      allergic asthma than male mice and studied allergic immune responses in the lung.
      METHODS: We compared allergic airway inflammation, i.e. methacholine (MCh)
      responsiveness, serum IgE, and cytokines, and the number of the different
      leucocytes in lungs of male and female BALB/c mice, twice-sensitized to ovalbumin
      (OVA) and subsequently challenged with OVA (OVA-mice) or phosphate-buffered
      saline (PBS-mice) aerosols on days 24-26, 30, and 31. RESULTS: OVA challenge
      significantly increased MCh responsiveness, numbers of eosinophils, CD4(+) T
      cells, CD4(+)/CD25(+) T cells, B cells, and levels of Thelper (Th)2 cytokines,
      total, and OVA-specific IgE. There was, however, also an effect of gender, with
      female mice responding to OVA challenges with higher numbers of eosinophils,
      CD4(+) T cells, B cells, and levels of IL-4, IL-13, IFN-gamma, total, and OVA
      specific IgE than male mice. In contrast, female PBS-mice had significantly lower
      percentages of regulatory CD4(+)/CD25(+) T cells than males (females 4.2+/-0.2%
      vs. males 5.3+/-0.1% of CD4(+) T cells, P<0.05). CONCLUSION: Female mice develop
      a more pronounced type of allergic airway inflammation than male mice after OVA
      challenge. The reduced percentage of regulatory T cells in the lungs of female
      PBS-mice may indicate that the level of these cells in the lung during the
      sensitization phase is important for the development and/or progression of an
      allergic immune response after multiple OVA challenges.

PMID- 16297150
TI  - Dancing with the enemy: the interplay of herpes simplex virus with dendritic
      cells.
AB  - Summary Herpes simplex virus (HSV) represents a smart pathogen, which displays
      both lytic and latent modes of interaction with its natural human host. In order
      to be optimally equipped for immune evasion and to reply to any attacks of the
      host during reactivation, HSV has developed a multitude of cleverly devised
      defence strategies. Dendritic cells (DC) as antigen-presenting cells located at
      the border zones of the body and the environment have been shown to play a
      crucial role as one of the first cells interacting with HSV beside epithelial
      cells, on one hand, and as important controllers of the viral spreading on the
      other hand. Here, we provide a research update about the interaction of HSV with
      DC and summarize the latest proceedings in this field.

PMID- 16297151
TI  - Defective signalling in salivary glands precedes the autoimmune response in the
      non-obese diabetic mouse model of sialadenitis.
AB  - The spontaneous non-obese diabetic (NOD) mouse model of Sjogren's syndrome
      provides a valuable tool to study the onset and progression of both the
      autoimmune response and secretory dysfunction. Our purpose was to analyse the
      temporal decline of salivary secretion in NOD mice in relation to the autoimmune
      response and alterations in various signalling pathways involved in saliva
      secretion within each salivary gland. A progressive loss of nitric oxide synthase
      activity in submandibular and parotid glands started at 12 weeks of age and
      paralleled the decline in salivary secretion. This defect was associated with a
      lower response to vasoactive intestinal peptide in salivary flow rate, cAMP and
      nitric oxide/cGMP production. No signs of mononuclear infiltrates or local
      cytokine production were detectable in salivary glands in the time period studied
      (10-16 weeks of age). Our data support a disease model for sialadenitis in NOD
      mice in which the early stages are characterized by defective neurotransmitter
      mediated signalling in major salivary glands that precedes the autoimmune
      response.

PMID- 16297152
TI  - Immunological control of methicillin-resistant Staphylococcus aureus (MRSA)
      infection in an immunodeficient murine model of thermal injuries.
AB  - Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is a
      major cause of sepsis in patients who are immunosuppressed by their burns. In
      this study, an immunological regulation of MRSA infection was attempted in a
      mouse model of thermal injury. SCIDbg mice were resistant to MRSA infection,
      while SCIDbgMN mice (SCIDbg mice depleted of neutrophils and macrophages (Mphi))
      were susceptible to the same infection. Also, thermally injured SCIDbg mice were
      shown to be susceptible to MRSA infection. On the other hand, the resistance of
      SCIDbgMN mice to the infection was completely recovered after an inoculation with
      Mphi from normal mice. However, anti-MRSA resistance was not shown in SCIDbgMN
      mice inoculated with Mphi from thermally injured mice. Mphi from MRSA-infected
      thermally injured mice were identified as alternatively activated Mphi, and Mphi
      from MRSA-infected unburned mice were characterized as classically activated
      Mphi. Mphi from thermally injured SCIDbg mice previously treated with 2
      carboxyethylgermanium sesquioxide (Ge-132) protected SCIDbgMN mice against MRSA
      infection. Ge-132 has been described as an inhibitor of alternatively activated
      Mphi generation. These results suggest that MRSA infection in thermally injured
      patients is controlled immunologically through the induction of anti-MRSA
      effector cells and elimination of burn-associated alternatively activated Mphi,
      which are cells that inhibit the generation of classically activated Mphi.

PMID- 16297153
TI  - Protective effect of intravenous immunoglobulin (IVIG) in an experimental model
      of pemphigus vulgaris.
AB  - Uncontrolled studies have found intravenous immunoglobulin (IVIG) to be effective
      in the treatment of pemphigus vulgaris (PV). The aim of this study was to
      evaluate the role of IVIG in preventing IgG autoantibodies binding to desmoglein
      3 and blister formation using a controlled experimental design. The ability of
      IVIG to affect the binding of IgG affinity purified from two patients with PV to
      desmoglein-3 in comparison to IgG from one donor, was conducted by enzyme-linked
      immunosorbent assay (ELISA). The specificity was confirmed by competition assay.
      We assessed the effect of IVIG on the induction of experimental-PV in CD1 newborn
      mice by subcutaneous subjection of IgG affinity purified from two patients with
      PV. The treatment was conducted by subcutaneous administration of IVIG together
      with IgG from the pemphigus patients or appropriate control. The skin of the
      newborns was examined 24-48 h later for blisters, and samples of the affected
      areas were analysed by immunohistochemistry. IVIG as a whole molecule and its
      F(ab)(2) portion inhibited the binding of anti-desmoglein-3 antibody to
      recombinant desmoglein-3 in a dose-dependent manner. The specificity was
      confirmed by competition assays. In-vivo, IVIG and its F(ab)(2) portion prevented
      blister formation in the newborn mice. Cutaneous lesions were noted only in the
      groups of newborn mice who were injected with IgG fractions from the PV patients.
      Immunopathological evaluation revealed that IVIG prevented the formation of
      acanthylosis with IgG deposition in the intercellular spaces. These results point
      to the efficacy of IVIG in the prevention of blister formation in an experimental
      PV model.

PMID- 16297155
TI  - Immunoglobulin treatment reduces atherosclerosis in apolipoprotein E-/- low
      density lipoprotein receptor-/- mice via the complement system.
AB  - Atherosclerosis is associated with activation of the immune system. Intravenously
      applied normal polyclonal immunoglobulins (IVIg) have broad therapeutic
      applications in the treatment of autoimmune and systemic inflammatory diseases.
      Recently, IVIg have been shown to inhibit atherogenesis in experimental animal
      models. To investigate the role of the complement system in this process, we used
      third complement component-deficient (C3(-/-)) and control atherosclerosis-prone
      apolipoprotein E (ApoE) and low-density lipoprotein receptor (LDLR) double knock
      out mice fed a normal diet. IVIg treatment reduced lesion fraction area in the
      aortic root of complement-sufficient mice whereas the lesion fraction area of C3(
      /-) mice was not affected. Thus, complement activation plays a role in the anti
      atherosclerotic effects of IVIg, possibly by C3-derived fragments generated
      through Fc-dependent complement activation.

PMID- 16297154
TI  - Anisakis simplex allergy: a murine model of anaphylaxis induced by parasitic
      proteins displays a mixed Th1/Th2 pattern.
AB  - The study of the singular hypersensitivity reactions to Anisakis simplex (A.s)
      proteins, may help us to undestand many of the unknown immune interactions
      between helmiths infections and allergy. We have developed a murine model of
      allergy to A. simplex, that mimics human A. simplex allergy to study the specific
      aspects of anaphylaxis induced by parasites. Male C3H/HeJ mice were
      intraperitoneally sensitized to A. simplex. Mice were then intravenous or orally
      challenged with A. simplex. Antigen-specific immunoglobulins, polyclonal IgE,
      anaphylactic symptoms, plasma histamine levels and cytokine profiles were
      determined. Comparative IgE immunoblot analyses were also performed. Specific
      IgE, IgG(1) and IgG(2a) were detected in sensitized mice since week 3. Polyclonal
      IgE raised and peaked with different kinetics. Intravenous A. simplex challenge
      produced anaphylaxis in mice, accompanied by plasma histamine release. Oral A.
      simplex challenge in similarly sensitized mice did not caused symptoms nor
      histamine release. Numerous A. simplex allergens were recognized by sensitized
      mouse sera, some of them similar to human serum. The A. simplex stimulated
      splenocytes released IL-10, IFN-gamma, IL-4, IL-13 and IL-5. We describe a new
      animal model of anaphylaxis. It exhibits characteristics of type I
      hypersensitivity reactions to Anisakis simplex similar to those observed in
      allergic humans. Different responses to i.v. or oral A. simplex challenges
      emerged, which did not reflect a window tolerization period. The cytokine profile
      developed (mixed Th(1)/Th(2) pattern) differed from the observed in classical
      models of anaphylaxis or allergy to food antigens. This model may permit to
      investigate the peculiar allergic reactions to parasitic proteins.

PMID- 16297156
TI  - Cytokine responses correlate differentially with age in infancy and early
      childhood.
AB  - The functional differentiation of immune cells at early age plays a central role
      in immune physiology, e.g. for the sufficient eradication of pathogens. However,
      imbalances in effector cell responses may also have an impact in the
      pathophysiology of childhood diseases such as atopy and autoimmune disorders. As
      information on immune cell responses in infancy and early childhood is scarce, we
      conducted an observational, cross-sectional study in healthy newborns (n = 18),
      infants and young children (n = 54) aged 1-96 months and adult controls (n = 19)
      to assess cytokine mRNA and protein expression upon phorbol 12-myristate 13
      actate/ionomycin stimulation and LPS-induced IL-12 expression in monocytes. The
      intracellular expression of interferon (IFN)-gamma, tumour necrosis factor (TNF)
      alpha (R = 0.748, P < 0.0001; R = 0.784, P < 0.0001, respectively) and
      interleukin (IL)-2 protein expression (R = 0.384, P = 0.008) was demonstrated to
      increase progressively with age. While a correlation between IL-4 protein
      expression and age was noted (R = 0.342, P = 0.007), the levels of IL-5 and IL-10
      protein expression tended to be regulated on an individual basis during infancy
      and early childhood. An age correlation was also observed for intracellular IL-12
      expression (R = 0.331, P = 0.009) in monocytes. These findings are valuable for
      further assessment of normal variations and maturation processes in immune cell
      responses and for the clinical-therapeutic monitoring of immunological status in
      various childhood diseases.

PMID- 16297157
TI  - Stable, soluble, high-affinity, engineered T cell receptors: novel antibody-like
      proteins for specific targeting of peptide antigens.
AB  - The recent development of T cell receptor phage display opens up the possibility
      of engineering human T cell receptors with antibody-like binding properties for
      cell-surface peptide antigens. In this review we briefly discuss recent
      developments in molecular targeting of peptide antigens. We then discuss
      potential clinical applications of engineered high-affinity T cell receptors in
      autoimmunity and cancer.

PMID- 16297158
TI  - Selective expansion of CD16highCCR2- subpopulation of circulating monocytes with
      preferential production of haem oxygenase (HO)-1 in response to acute
      inflammation.
AB  - Monocytes are composed of two distinct subpopulations in the peripheral blood as
      determined by their surface antigen expressions, profiles of cytokine production
      and functional roles played in vivo. We attempted to delineate the unique
      functional roles played by a minor CD16(high)CCR2(-) subpopulation of circulating
      monocytes. They produced significant levels of interleukin (IL)-6 and tumour
      necrosis factor (TNF)-alpha, but very low levels of IL-10 upon in vitro
      stimulation. Characteristic profiles of cytokine production were confirmed by
      stimulating purified subpopulations of monocytes after cell sorting. It was
      noteworthy that freshly isolated CD16(high)CCR2(-) monocyte subpopulations
      produced significant levels of haem oxygenase (HO)-1, whereas the major
      CD16(low)CCR2(+) subpopulation produced little. These results were contrary to
      the generally accepted notion that the CD16(high)CCR2(-) monocyte subpopulation
      plays a predominantly proinflammatory role in vivo. The CD16(high)CCR2(-)
      subpopulation increased in Kawasaki disease and influenza virus infection. In
      accord with this, HO-1 mRNA expression by mononuclear cells was significantly
      increased in these illnesses. These results indicate that CD16(high)CCR2(-)
      subpopulations are of a distinct lineage from CD16(low)CCR2(+) monocytes. More
      importantly, they may represent a monocyte subpopulation with a unique functional
      role to regulate inflammation by producing HO-1 in steady state in vivo.

PMID- 16297159
TI  - Interferon-alpha2a is sufficient for promoting dendritic cell immunogenicity.
AB  - Type I interferons (IFNs) are widely used therapeutically. IFN-alpha2a in
      particular is used as an antiviral agent, but its immunomodulatory properties are
      poorly understood. Dendritic cells (DCs) are the only antigen-presenting cells
      able to prime naive T cells and therefore play a crucial role in initiating the
      adaptive phase of the immune response. We studied the effects of IFN-alpha2a on
      DC maturation and its role in determining Th1/Th2 equilibrium. We found that IFN
      alpha2a induced phenotypic maturation of DCs and increased their allostimulatory
      capacity. When dendritic cells were stimulated simultaneously by CD40 ligation
      and IFN-alpha2a, the production of interleukin (IL)-10 and IL-12 was increased.
      In contrast, lipopolysaccharide (LPS) stimulation in the presence of IFN-alpha2a
      mainly induced IL-10 release. The production of IFN-gamma and IL-5 by the
      responder naive T cells was also amplified in response to IFN-alpha2a-treated
      DCs. Furthermore, IL-12 production by IFN-alpha2a-treated DCs was enhanced
      further in the presence of anti-IL-10 antibody. Different results were obtained
      when DCs were treated simultaneously with IFN-alpha2a and other maturation
      factors, in particular LPS, and then stimulated by CD40 ligation 36 h later.
      Under these circumstances, IFN-alpha2a did not modify the DC phenotype, and the
      production of IL-10/IL-12 and IFN-gamma/IL-5 by DCs and by DC-stimulated naive T
      cells, respectively, was inhibited compared to the effects on DCs treated with
      maturation factors alone. Altogether, this work suggests that IFN-alpha2a in
      isolation is sufficient to promote DC activation, however, other concomitant
      events, such as exposure to LPS during a bacterial infection, can inhibit its
      effects. These results clarify some of the in vivo findings obtained with IFN
      alpha2a and have direct implications for the design of IFN-alpha-based vaccines
      for immunotherapy.

PMID- 16297160
TI  - Macrophage activation switching: an asset for the resolution of inflammation.
AB  - Macrophages play a central role in inflammation and host defence against
      microorganisms, but they also participate actively in the resolution of
      inflammation after alternative activation. However, it is not known whether the
      resolution of inflammation requires alternative activation of new resting
      monocytes/macrophages or if proinflammatory activated macrophages have the
      capacity to switch their activation towards anti-inflammation. In order to answer
      this question, we first characterized differential human macrophage activation
      phenotypes. We found that CD163 and CD206 exhibited mutually exclusive induction
      patterns after stimulation by a panel of anti-inflammatory molecules, whereas
      CCL18 showed a third, overlapping, pattern. Hence, alternative activation is not
      a single process, but provides a variety of different cell populations. The
      capacity of macrophages to switch from one activation state to another was then
      assessed by determining the reversibility of CD163 and CD206 expression and of
      CCL18 and CCL3 production. We found that every activation state was rapidly and
      fully reversible, suggesting that a given cell may participate sequentially in
      both the induction and the resolution of inflammation. These findings may provide
      new insight into the inflammatory process as well as new fields of investigation
      for immunotherapy in the fields of chronic inflammatory diseases and cancer.

PMID- 16297161
TI  - Protein kinase-A-dependent osteoprotegerin production on interleukin-1
      stimulation in human gingival fibroblasts is distinct from periodontal ligament
      fibroblasts.
AB  - Periodontitis, a chronic inflammatory disease, is characterized by increased
      expression of interleukin (IL)-1 and other inflammatory mediators resulting in
      extensive osteoclast formation and bone loss. Expression of receptor activator of
      nuclear factor kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin
      (OPG), by osteoblasts is important to regulate osteoclast differentiation. The
      aim of the present study was to investigate the regulatory effects of IL-1 on
      RANKL and OPG production by mesenchymal fibroblasts in periodontal tissue. Human
      gingival fibroblasts (HGF) and periodontal ligament fibroblasts (PDL) were
      stimulated with IL-1alpha with or without protein synthesis inhibitor
      cycloheximide (CHX), protein kinase A (PKA) inhibitors, protein kinase C (PKC)
      inhibitors and prostaglandin E(2) (PGE(2)) inhibitor. In some experiments, the
      cultured cells were directly stimulated with either PKA or PKC activators. In
      HGF, IL-1alpha-stimulated OPG mRNA expression was high and could be reduced by
      CHX. PKA inhibitor completely abrogated IL-1alpha-induced OPG mRNA expression and
      OPG production. Endogenous PGE(2) further enhanced IL-1alpha-induced OPG
      production in HGF. In PDL, RANKL mRNA expression was greatly augmented by IL
      1alpha. IL-1alpha induced OPG mRNA expression and protein production. PKC
      inhibitor partially reduced IL-1alpha-induced OPG production and PKC activator
      enhanced OPG production in PDL. The IL-1alpha-stimulated OPG mRNA expression in
      HGF was greater than PDL. These results provide new evidence for the possible
      osteoclastogenesis-inhibitory function of HGF through PKA activity pathway. PDL
      utilized PKC for OPG production. Thus, we emphasize that HGF and PDL have
      different characteristics of host defence mechanism against inflammatory process.

PMID- 16297162
TI  - Correlations among measles virus-specific antibody, lymphoproliferation and
      Th1/Th2 cytokine responses following measles-mumps-rubella-II (MMR-II)
      vaccination.
AB  - Immunity to measles is conferred by the interplay of humoral and cellular immune
      responses, the latter being critical in maintaining long-term recall response.
      Therefore, it is important to evaluate measles-specific humoral and cellular
      immunity in populations several years after vaccination and understand the
      correlations among these measures of immunity. We examined measles-specific
      antibodies, lymphoproliferation and the Th1/Th2 signature cytokines, interferon
      (IFN)-gamma and interleukin (IL)-4, in a population-based cohort of healthy
      children from Olmsted County, Minnesota after two doses of measles-mumps-rubella
      II (MMR-II) vaccine. We detected positive measures of measles-specific cellular
      and humoral immunity in the majority of our study population. However, a small
      proportion of subjects demonstrated an immune response skewed towards the Th2
      type, characterized by the presence of either IL-4 and/or measles-specific
      antibodies and a lack of IFN-gamma production. Further, we observed a significant
      positive correlation between lymphoproliferation and secretion of IFN-gamma (r =
      0.20, P = 0.0002) and IL-4 (r = 0.15, P = 0.005). Measles antibody levels were
      correlated with lymphoproliferation (r = 0.12, P = 0.03), but lacked correlation
      to either cytokine type. In conclusion, we demonstrated the presence of both long
      term cellular and humoral responses after MMR-II vaccination in a significant
      proportion of study subjects. Further, a positive correlation between
      lymphoproliferation and IL-4 and IFN-gamma suggests that immunity to measles may
      be maintained by both Th1 and Th2 cells. We speculate that the Th2 biased
      response observed in a subset of our subjects may be insufficient to provide long
      term immunity against measles. Further examination of the determinants of Th1
      versus Th2 skewing of the immune response and long-term follow-up is needed.

PMID- 16297163
TI  - Chronic fatigue syndrome is associated with diminished intracellular perforin.
AB  - Chronic fatigue syndrome (CFS) is an illness characterized by unexplained and
      prolonged fatigue that is often accompanied by abnormalities of immune, endocrine
      and cognitive functions. Diminished natural killer cell cytotoxicity (NKCC) is a
      frequently reported finding. However, the molecular basis of this defect of in
      vitro cytotoxicy has not been described. Perforin is a protein found within
      intracellular granules of NK and cytotoxic T cells and is a key factor in the
      lytic processes mediated by these cells. Quantitative fluorescence flow cytometry
      was used to the intracellular perforin content in CFS subjects and healthy
      controls. A significant reduction in the NK cell associated perforin levels in
      samples from CFS patients, compared to healthy controls, was observed. There was
      also an indication of a reduced perforin level within the cytotoxic T cells of
      CFS subjects, providing the first evidence, to our knowledge, to suggest a T cell
      associated cytotoxic deficit in CFS. Because perforin is important in immune
      surveillance and homeostasis of the immune system, its deficiency may prove to be
      an important factor in the pathogenesis of CFS and its analysis may prove useful
      as a biomarker in the study of CFS.

PMID- 16297164
TI  - The association of anti-phospholipid antibodies with parity in placental malaria.
AB  - Anti-phospholipid antibodies (aPL) are autoantibodies associated with both
      infections and the pathogenesis of certain pregnancy complications. In the
      latter, but not the former, aPL are dependent on a co-factor, beta(2)
      glycoprotein I (beta2GPI), which can also be used as an antigen for detection of
      such aPL in pregnancy. A cross-sectional study was carried out on serum samples
      from Kumasi, Ghana, to determine the occurrence and beta2GPI-dependence of aPL in
      placental malaria. Anti-cardiolipin, anti-phosphatidylserine and anti-beta2GPI
      enzyme-linked immunosorbent assays (ELISAs) were performed on sera from 103 HIV
      non-infected gravid women. Placental malaria, both active and past infection, was
      diagnosed in 33/103 (32%) based on placental histology. In multiparae, beta2GPI
      independent IgM antibodies to cardiolipin (P = 0.018) and phosphatidylserine (P =
      0.009) were observed, which were most pronounced in past placental malaria
      infection. In primiparae, no association emerged between aPL and placental
      malaria. Trends for improved clinical parameters were identified in infected
      women with levels of anti-cardiolipin beyond the 99th multiple of the median for
      a healthy, non-malarious population. This study in placental malaria reports
      parity associations of beta2GPI-independent aPL profiles, and does not support a
      role for beta2GPI-dependent aPL. It is of significance in the context of the
      known parity differences in pregnancy malaria immunity.

PMID- 16297165
TI  - Predominance of type 1 CD4+ T cells in human abdominal aortic aneurysm.
AB  - The functional repertoire of T cells in abdominal aortic aneurysm (AAA) and the
      exact nature of aortic wall adaptive cellular immune responses still remains a
      matter of debate. In this study, we sought to determine whether type 1 or type 2
      responses occur predominantly in human aneurysmal aortic lesions. We first
      examined the phenotype and cytokine secretion profile of T lymphocytes freshly
      isolated from aneurysmal aortic wall for comparison with their circulating
      counterparts using flow cytometry. We found that both populations of infiltrating
      CD4(+) and CD8(+)T cells displayed a unique activated memory phenotype. In
      addition, we identified the presence in human aneurysmal aortic lesion of CD4(+)T
      cells producing high levels of interferon (IFN)-gamma but not interleukin (IL)-4,
      reflecting their type 1 nature. Quantitative analysis of cytokine gene expression
      confirmed increased IFN-gamma transcript levels in infiltrating cells compared to
      controls. We next analysed aortic wall responses using LightCycler-based
      quantitative real-time reverse transcription-polymerase chain reaction. Compared
      to control non-diseased aortic samples, we demonstrated that whole AAA tissues
      exhibited high mRNA levels of IFN-gamma but not IL-4. Overexpression of the
      transcription factor T-bet in the absence of significant GATA-3 expression
      further assessed the type 1 polarization of aortic wall immune responses. These
      findings indicate that type 1 CD4(+)T cells predominate in human AAA lesions.
      This study has important implications for the pathogenesis of aneurysm disease.
      Through the production of IFN-gamma, T cells may indeed contribute to orchestrate
      extracellular matrix remodelling.

PMID- 16297166
TI  - Screening of an Echinococcus granulosus cDNA library with IgG4 from patients with
      cystic echinococcosis identifies a new tegumental protein involved in the immune
      escape.
AB  - The worldwide problem of chronic Echinococcus granulosus disease calls for new
      parasite-derived immunomodulatory molecules. By screening an E. granulosus cDNA
      library with IgG4 from patients with active cystic echinococcosis, we identified
      a cDNA that encodes a predicted partial protein that immunofluorescence studies
      localized in the protoscolex tegument and on the germinal layer of cyst wall. We
      named this protein EgTeg because the 105 amino acid sequence scored highest
      against a family of Schistosoma tegumental proteins. Evaluating the role of EgTeg
      in the human early inflammatory response we found that EgTeg significantly
      inhibited polymorphonuclear cell (PMN) chemotaxis. Cytometric analysis of
      intracellular cytokines disclosed a significantly higher percentage of cells
      producing IL-4 than IFN-gamma (P = 0.001, Student's t-test) in T lymphocytes from
      patients with cystic echinococcosis stimulated with EgTeg. EgTeg induced weak Th1
      dependent proliferation in 42% of patients' peripheral blood mononuclear cells.
      In immunoblotting (IB) analysis of total IgG and IgG subclass responses to EgTeg
      in patients with cystic echinococcosis, patients with other parasitoses, patients
      with cystic lesions and healthy controls, total IgG specific to EgTeg yielded
      high sensitivity (73%) but low specificity (44%) precluding its use in
      immunodiagnosis. Conversely, IgG4 specific to EgTeg gave acceptable sensitivity
      (65%) and high specificity (89%) suggesting its use in immunodiagnosis to confirm
      ultrasound documented cysts suggestive of E. granulosus. Because the new
      tegumental antigen EgTeg inhibits chemotaxis, induces IL-4-positive T lymphocytes
      and noncomplement fixing antibodies (IgG4) it is an immunomodulatory molecule
      associated with chronic infection.

PMID- 16297167
TI  - Identification of paramyosin T cell epitopes associated with human resistance to
      Schistosoma mansoni reinfection.
AB  - Paramyosin, a Schistosoma mansoni myoprotein associated with human resistance to
      infection and reinfection, is a candidate antigen to compose a subunit vaccine
      against schistosomiasis. In this study, 11 paramyosin peptides selected by
      TEPITOPE algorithm as promiscuous epitopes were produced synthetically and tested
      in proliferation and in vitro human leucocyte antigen (HLA)-DR binding assays. A
      differential proliferative response was observed in individuals resistant to
      reinfection compared to individuals susceptible to reinfection in response to
      Para (210-226) peptide stimulation. In addition, this peptide was able to bind to
      all HLA-DR molecules tested in HLA-DR binding assays, confirming its promiscuity.
      Para (6-22) and Para (355-371) were also shown to be promiscuous peptides,
      because they were able to bind to the six and eight most prevalent HLA-DR alleles
      used in HLA-DR binding assays, respectively, and were also recognized by T cells
      of the individuals studied. These results suggest that these paramyosin peptides
      are promising antigens to compose an anti-schistosomiasis vaccine.

PMID- 16297168
TI  - Interleukin (IL)-2 and IL-12 responses to Chlamydia trachomatis infection in
      adolescents.
AB  - Chlamydia trachomatis infects epithelial cells at the mucosal surface. While in
      vitro and animal studies have shown changes in mucosal T(H)1-associated cytokines
      in the presence of C. trachomatis infection and with its progression to the upper
      genital tract or clearance, in vivo cytokine responses to chlamydial infection in
      humans are not well understood. Using a quantitative enzyme-linked immunosorbent
      assay (ELISA), we examined the endocervical production of two T(H)1-associated
      cytokines, i.e. interleukin (IL)-2 and IL-12, in relation to C. trachomatis
      infection in adolescents. At a randomly selected visit for 396 females, median
      endocervical IL-2 levels were significantly lower (190 versus 283 pg/ml, P =
      0.02) and median IL-12 levels significantly higher (307 versus 132 pg/ml, P <
      0.001) in subjects testing positive versus negative for C. trachomatis. These
      divergent T(H)1-associated cytokine responses were: (1) confirmed in paired
      analyses of 96 individuals before and after infection within 6-month intervals,
      (2) reversible in 97 patients who cleared infection during consecutive visits,
      (3) not attributable to sociodemographic factors or other genital infections and
      (4) independent of common genetic variants at the IL2 and IL12B loci associated
      previously with differential gene expression. From these findings we infer that
      increased IL-12 and decreased IL-2, observed commonly during mucosal
      inflammation, are important features of mucosal immune defence against C.
      trachomatis infection.

PMID- 16297169
TI  - Dendritic cell immunizations alone or combined with low doses of interleukin-2
      induce specific immune responses in melanoma patients.
AB  - Dendritic cell (DC)-based therapy has proved to be effective in patients with a
      variety of malignancies. However, an optimal immunization protocol using DCs and
      the best means for delivering antigens has not yet been described. In this study,
      20 patients with malignant melanoma in stages III or IV were vaccinated with
      autologous DCs pulsed with a melanoma cell lysate, alone (n = 13) or in
      combination with low doses of subcutaneous (s.c.) interleukin (IL)-2 injections
      (n = 7), to assess toxicity, immunological and clinical responses. Monocyte
      derived DCs were morphological, phenotypic and functionally characterized in
      vitro. Peripheral blood mononuclear cells (PBMC), harvested from patients either
      prior to and after the treatment, were analysed using enzyme-linked immunosorbent
      spot (ELISPOT). After vaccination, 50% of the patients tested (seven of 13) from
      the first group and (three of seven) from the second, showed an increase in
      interferon (IFN)-gamma production in response to allogeneic melanoma cell lines
      but not to controls. Four of five tested human leucocyte antigen (HLA)-A2(+)
      patients with anti-melanoma activity also showed specific T cell responses
      against peptides derived from melanoma-associated antigens. Delayed type IV
      hypersensitivity reaction (DTH) against melanoma cell lysate was observed in six
      of 13 patients from the group treated with DC vaccines only and four of seven
      from the group treated with the combination of DCs and IL-2. Significant
      correlations were found between DTH-positive responses against tumour lysate and
      both disease stability and post-vaccination survival on the stage IV patients.
      There were no toxicities associated with the vaccines or evidence of autoimmunity
      including vitiligo. Furthermore, no significant enhancement was observed as a
      result of combining DC vaccination with IL-2. Our data suggest that autologous
      DCs pulsed with tumour lysate may provide a standardized and widely applicable
      source of melanoma specific antigens for clinical use. It is safe and causes no
      significant side effects and has been demonstrated to be partially efficient at
      triggering effective anti-melanoma immunity.

PMID- 16297170
TI  - The glycans deficiencies of macromolecular IgA1 is a contributory factor of
      variable pathological phenotypes of IgA nephropathy.
AB  - Recent evidence has suggested that IgA1-containing macromolecules and the
      glycosylation of IgA1 in sera from patients with IgAN might involve the
      pathogenesis of IgAN. However, whether the different histological phenotypes can
      be attributed or not to the aberrant glycosylation of macromolecular IgA1 has not
      yet been elucidated. The aim of the current study is to investigate the
      glycosylation of IgA1 molecules in serum IgA1-containing macromolecules and their
      association with pathological phenotypes of IgAN. Sera was collected from 40
      patients with IgAN and 20 donors. Twenty patients had mild mesangial
      proliferative IgAN, the remaining 20 had focal proliferative sclerosing IgAN.
      Polyethylene glycol 6000 was used to precipitate the macromolecules from sera of
      patients and controls. Biotinylated lectins were used in an enzyme-linked
      immunosorbent assay (ELISA) to examine different glycans on IgA1 molecules. The
      alpha2,6 sialic acid was detected by elderberry bark lectin (SNA) and the
      exposure of terminal galactose (Gal) and N-acetylgalactosamine (GalNAc) were
      detected by Arachis hypogaea (PNA) and Vilsa villosa lectin (VVL), respectively.
      The IgA1 glycans levels corrected by IgA1 concentrations were compared between
      patients and controls. Reduced terminal alpha2,6 sialic acid of IgA1 (79.89 +/-
      25.17 versus 62.12 +/- 24.50, P = 0.034) was demonstrated only in precipitates
      from sera of patients with focal proliferative sclerosing IgAN, compared with
      those from controls. Reduced galactosylation of IgA1 molecules in precipitates
      was demonstrated in patients with both mild mesangial proliferative IgAN and
      focal proliferative sclerosing IgAN compared with normal controls (24.52 +/-
      18.71 versus 76.84 +/- 32.59 P = 0.000 and 33.48 +/- 25.36 versus 76.84 +/- 32.59
      P = 0.000). However, no significant difference was found in IgA1 glycosylation in
      the supernatant between patients and normal controls (P > 0.05). The
      glycosylation deficiency of IgA1 existed only in serum IgA1-containing
      macromolecules of patients with IgAN, and was associated with the renal
      pathological phenotypes. This suggests that aberrant glycosylation of IgA1 in
      serum macromolecules might be a contributory factor in the pathogenesis of IgAN.

PMID- 16297171
TI  - Common variable immunodeficiency and the complement system; low mannose-binding
      lectin levels are associated with bronchiectasis.
AB  - The importance of the innate immune system, including mannose-binding lectin and
      the complement system, in common variable immunodeficiency is unclear. The
      objective of this study was to evaluate mannose-binding lectin and the complement
      system in relation to clinical and immunological parameters in patients with
      common variable immunodeficiency. Circulating levels of mannose-binding lectin,
      complement components, complement activation products and functional capacity of
      complement pathways were correlated to clinical features within 71 patients and
      compared with 30 healthy controls. The main findings were; the patients had signs
      of increased complement activation significantly associated with signs of
      autoimmunity and immunological hyperactivity; there were no signs of deficiencies
      of the classical and alternative complement pathways in the patient group; the
      prevalence of lectin pathway deficiency was the same in patients and controls,
      but patients with increased frequency of lower respiratory tract infections or
      bronchiectasis had lower capacity of the lectin pathway than patients without
      these features (P = 0.002 and 0.004, respectively); the serum concentration of
      mannose-binding lectin was inversely correlated to the frequency of lower
      respiratory tract infections (P = 0.002) and bronchiectasis (P = 0.01). We
      conclude that patients with common variable immunodeficiency have no increased
      frequency of complement deficiencies but signs of increased complement
      activation. Our findings suggest that mannose-binding lectin and the lectin
      complement pathway may protect against lower respiratory tract infection and
      bronhiectasis in patients with common variable immunodeficiency.

PMID- 16297175
TI  - Pemphigus: pathogenesis, pharmacology and progress: a meeting report of pemphigus
      2005--progress and future directions, held June 16-17, 2005 in Bethesda, Maryland
      (USA).

PMID- 16297176
TI  - Sebaceous glands and the prostaglandin pathway--key stones of an exciting mosaic.

PMID- 16297172
TI  - The immune responses to human and microbial heat shock proteins in periodontal
      disease with and without coronary heart disease.
AB  - The human 60 kDa and microbial 65 kDa heat shock proteins (HSP) have been
      implicated in the pathogenesis of chronic periodontitis (P) and coronary heart
      disease (CHD). We have studied four male non-smoking cohorts of 81 subjects,
      matched for age. Group (a) consisted of a healthy group with minimal gingivitis
      (n = 18), group (b) were patients with P (n = 23), group (c) patients with CHD
      and minimal gingivitis (n = 20) and group (d) patients with CHD and P (n = 20). T
      cells separated from peripheral blood were found to be primed to both microbial
      HSP65 and human HSP60 but significant CD4, human leucocyte antigen (HLA) class II
      restricted proliferative responses were found only with the human HSP60 in
      patients with P (P < 0.001) and CHD without (P < 0.001) or with (P < 0.00001)
      periodontitis. Dose-dependent inhibition of T cell proliferative responses was
      carried out to determine the receptors involved in recognition of HSP60 and
      HSP65. Monoclonal antibodies to CD14 showed inhibition of T cell proliferation
      stimulated by both HSP60 and HSP65, consistent with the role of CD14 as a
      receptor for these HSPs in P and CHD. The toll-like receptor 2 (TLR-) and TLR-4
      were then studied and these showed that TLR-4 was recognized by microbial HSP65,
      whereas TLR-2 was recognised by human HSP60 in both P and CHD. However, a
      dissociation was found in the HSP60 and TLR4 interaction, as TLR4 appeared to
      have been recognized by HSP60 in P but not in CHD. The results suggest an
      autoimmune or cross-reactive CD4(+) class II-restricted T cell response to the
      human HSP60 in P and CHD. Further studies are required to determine if there is a
      common epitope within HSP60 that stimulates T cell proliferation in P and CHD.

PMID- 16297177
TI  - Lamin processing comes of age.

PMID- 16297178
TI  - Defining upstream elements of psoriasis pathogenesis: an emerging role for
      interferon alpha.

PMID- 16297179
TI  - Sunlight, vitamin D, and the innate immune defenses of the human skin.

PMID- 16297180
TI  - Activation of molecular adaptation to sunlight--a new approach to
      photoprotection.

PMID- 16297181
TI  - P53 family activities in development and cancer: relationship to melanocyte and
      keratinocyte carcinogenesis.

PMID- 16297182
TI  - Augmentation of lipogenesis by 15-deoxy-Delta12,14-prostaglandin J2 in hamster
      sebaceous glands: identification of cytochrome P-450-mediated 15-deoxy-Delta12,14
      prostaglandin J2 production.
AB  - Prostaglandins (PGs) play important roles in the regulation of cutaneous cell
      functions under physiological and pathological conditions. In this study, we
      examined the involvement of PGs in sebocyte lipogenesis using non-steroidal anti
      inflammatory drugs in vivo and in vitro. Hamster auricle sebocytes spontaneously
      differentiated to accumulate intracellular triacylglycerol (TG), under which the
      relative levels of 15-deoxy-Delta(12,14)-PGJ2 (15d-PGJ2) to PGF(2alpha) and PGE2
      increased. 15d-PGJ2 was found to augment the formation of lipid droplets, which
      was because of an increase of TG synthesis by diacylglycerol acyltransferase
      (DGAT). Furthermore, sebocytes constitutively produced cyclooxygenase 2 (COX-2),
      but not COX-1, in vivo and in vitro. When sebocytes were treated with COX
      inhibitors such as indomethacin, diclofenac, or NS-398, the production of
      PGF(2alpha) and PGE2 decreased. The production of 15d-PGJ2, however, was
      increased in these inhibitor-treated sebocytes. In addition, indomethacin,
      diclofenac, and NS-398 augmented the synthesis of TG along with the increase in
      DGAT activity. Similarly, topical administration of indomethacin to hamster
      auricles caused the development of sebaceous glands with the augmentation of
      sebum deposition in vivo. Furthermore, indomethacin and NS-398-augmented 15d-PGJ2
      production and TG synthesis were suppressed by a non-selective cytochrome P-450
      (CYP) inhibitor, SKF-525A. A ligand activator of peroxisome proliferation
      activating receptor gamma (PPARgamma), troglitazone-induced synthesis of TG,
      however, was not altered even in the presence of SKF-525A. These results suggest
      that 15d-PGJ2 is a crucial stimulator of sebocyte lipogenesis by augmenting DGAT
      mediated synthesis of TG. In addition to the COX-2-dependent pathway of PG
      synthesis, our findings suggest a sebocyte-specific pathway of 15d-PGJ2
      production by CYP, the activity of which may be evoked by inhibiting COX-2.

PMID- 16297183
TI  - Igf-I signalling controls the hair growth cycle and the differentiation of hair
      shafts.
AB  - Mesenchymal-epithelial signalling between the dermal papilla and the hair matrix
      regulates cell proliferation and differentiation in mature hair follicles. The
      molecular basis of these interactions is largely unexplored. According to its
      expression in the dermal papilla, IGF-I is likely involved in reciprocal
      signalling. To examine its biological function in pelage follicles further, we
      generated transgenic mice that express Igf-I in the inner root sheath and the
      medulla using an involucrin promoter fragment. We demonstrate that Igf-I affects
      follicular proliferation, tissue remodelling, and the hair growth cycle, as well
      as folliclular differentiation. Transgenic skin temporarily lacks visible adipose
      tissue in telogen. The onset of the second, aberrant growth phase is markedly
      retarded. Transgenic guard hairs are significantly elongated and a small fraction
      of hair follicles is severely disoriented. The microscopic appearance of most
      hair shafts is altered and, strikingly, Igf-I transgenic mice lack hairs with a
      zigzag shape due to the suppression of hair shaft bending. All transgenic effects
      are partially compensated by ectopic expression of Igfbp3. Finally, Pdgfralpha
      was identified as the first molecular target that is affected in Igf-I transgenic
      mice. In summary, our data identify IGF-I signalling as an important mitogenic
      and morphogenetic regulator in hair follicle biology.

PMID- 16297184
TI  - Proteolytic processing of the laminin alpha3 G domain mediates assembly of
      hemidesmosomes but has no role on keratinocyte migration.
AB  - Laminin-5 (Lm5), the major adhesion ligand of basal epithelial cells, undergoes
      complex extracellular proteolytic processing that influences cell adhesion and
      migration. In tumor cell lines, the proteolytic truncation of the C-terminal G
      domain of the Lm alpha3 chain induces assembly of hemidesmosomes and
      downregulates cell migration. To define the biological functions of the alpha3 G
      domain processing in physiological conditions, we have expressed a series of
      mutant alpha3 complementary DNA in human primary alpha3-null keratinocytes
      immortalized by human papillomavirus E6E7 (HKalpha3 cells). Using monolayer and
      organotypic cell cultures we show that: (1) the hinge region between subdomains
      G3 and G4 carries the proteolytic cleavage sites; (2) nucleation of the
      hemidesmosomal proteins is independent of the proteolytic maturation of the
      alpha3 G domain, whereas formation of mature hemidesmosomes relies on proteolytic
      cleavage of alpha3; and (3) the proteolytic processing plays no role in cell
      migration, which suggests that nucleation of hemidesmosomal structures in culture
      does not reflect the migratory potential of the epithelial cells. Our results
      also demonstrate that HKalpha3 cells are a unique model system, which will be
      useful to dissect the functions and molecular interactions of Lm5.

PMID- 16297185
TI  - The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index): an
      outcome instrument for cutaneous lupus erythematosus.
AB  - We developed and validated a measurement instrument (CLASI-Cutaneous Lupus
      Erythematosus Disease Area and Severity Index) for lupus erythematosus that could
      be used in clinical trials. The instrument has separate scores for damage and
      activity. A group of seven American Dermato-Rheumatologists and the "American
      College of Rheumatology Response Criteria Committee on SLE (systemic lupus
      erythematosus)" assessed content validity. After a preliminary session, we
      conducted standardized interviews with the raters and made slight changes to the
      instrument. The final instrument was evaluated by five dermatologists and six
      residents who scored nine patients to estimate inter- and intra-rater reliability
      in two sessions. Consultation with experts has established content validity of
      the instrument. Reliability studies demonstrated an intra-class correlation
      coefficient (ICC) for inter-rater reliability of 0.86 for the activity score (95%
      confidence interval (CI) = 0.73-0.99) and of 0.92 for the damage score (95% CI =
      0.85-1.00). The Spearman's rho (Sp) for intra-rater reliability for the activity
      score was 0.96 (95% CI = 0.89 to 1.00) and for the damage score Sp was 0.99 (95%
      CI = 0.97-1.00). Clinical responsiveness needs to be evaluated in a prospective
      clinical trial, which is ongoing.

PMID- 16297186
TI  - The association between HLA DR, DQ antigens, and vulval lichen sclerosus in the
      UK: HLA DRB112 and its associated DRB112/DQB10301/04/09/010 haplotype confers
      susceptibility to vulval lichen sclerosus, and HLA DRB10301/04 and its associated
      DRB10301/04/DQB10201/02/03 haplotype protects from vulval lichen sclerosus.
AB  - Lichen sclerosus (LS) is considered to have an immunogenetic background. Several
      small studies, using serological typing, have reported that HLA-DR11, DR12, and
      DQ7 were increased in LS, with DR17 less frequent. This study aimed to validate
      and detect new HLA-DR and DQ associations with LS in females and its
      characteristic clinical parameters. The cases, 187 female LS patients, and 354
      healthy controls were all UK North Europeans. PCR-sequence specific primers
      method was applied to genotype the HLA-DR, DQ polymorphisms that correspond to 17
      serologically defined DR and seven DQ antigens. Statistical analysis was
      performed with two-tailed Fisher's exact test with Bonferroni adjustment (p value
      after Bonferrroni adjustment, Pc). We found increased frequency of DRB1*12 (DR12)
      (11.2%vs 2.5%, pc < 0.01) and the haplotype DRB1*12/DQB1*0301/04/09/010 (11.2%vs
      2.5%, p < 0.001, pc < 0.05), and a lower frequency of DRB1*0301/04 (DR17)
      (11.8%vs 25.8%, pc < 0.01) and the haplotype
      DRB1*03/DQB1*02DRB1*0301/DQB1*0201/02/03 (11.2%vs 24.6%, pc < 0.0001) in patients
      compared with controls. HLA DR and DQ antigens were not associated with time of
      onset of disease, site of involvement, structural changes of genitals, and
      response to treatment with potent topical steroids. In conclusion, HLA-DR and DQ
      antigens or their haplotypes appear to be involved in both susceptibility to and
      protection from LS.

PMID- 16297187
TI  - Tissue-specific expression of the ABCC6 gene.
AB  - The ABCC6 gene encodes MRP6, a member of the multidrug resistance-associated
      protein (MRP) family. Interest in ABCC6/MRP6 derives, in part, from the fact that
      mutations in this gene/protein system have been identified in families with
      pseudoxanthoma elasticum (PXE). Early studies indicated that ABCC6 is expressed
      primarily in the liver and to a lesser extent in the kidney, but more recently a
      widespread distribution has been suggested. To explore the tissue-specific
      expression of ABCC6, we first examined various mouse tissues by RT-PCR. The
      results indicated high levels of mRNA in the liver, whereas low level of
      expression was noted in the kidney and small intestine. To explore other tissues
      in which initial RT-PCR was essentially negative, a second-round nested PCR was
      performed, which revealed expression also in the brain, tongue, stomach, and eye.
      Unexpectedly, however, distinct PCR products of smaller molecular weight were
      noted in these tissues. Subcloning and sequencing of these PCR products indicated
      that they reflected aberrant splicing in the 3' end of the ABCC6 mRNA, resulting
      in each case in a premature termination codon. Similar results were noted with RT
      PCR analysis using RNA isolated from cultured human epidermal keratinocytes and
      dermal fibroblasts. Collectively, our results confirm high level of expression of
      ABCC6 in the liver and the kidney, whereas very low level of expression in a
      variety of other tissues was noted. The results have implications for mutation
      detection strategies in PXE by RT-PCR, and they further support the notion that
      PXE is a primary metabolic disorder.

PMID- 16297188
TI  - Systematic linkage disequilibrium analysis of SLC12A8 at PSORS5 confirms a role
      in susceptibility to psoriasis vulgaris.
AB  - The gene for solute carrier family 12 member A8 has recently been proposed as a
      candidate gene for psoriasis susceptibility (PSORS5) on chromosome 3q based on
      association of five single nucleotide polymorphisms (SNP) in Swedish patients. To
      investigate whether this locus is relevant for German psoriasis vulgaris (PsV)
      patients, we analyzed a group of 210 trios and a case-control group including 375
      patients. Based on our investigation of the linkage disequilibrium (LD) structure
      of SLC12A8, we assayed 35 haplotype tag SNP and grouped them into nine LD-blocks.
      In the case-control study, we detected an association for six SNP and three LD
      based haplotypes. Association was strongest for ss35527511 (chi2 = 11.224, p =
      0.0008) and haplotype E-2 (chi2 = 11.788, p = 0.00059) and independent of the
      presence of an HLA-associated PSORS1 risk allele. Through extended haplotype
      analysis, we could show that two independent association signals exist in
      SLC12A8, suggesting allelic heterogeneity. None of the SNP showed association in
      trios, apart from a weak association of rs2228674 (transmission disequilibrium
      test statistics p = 0.048), probably due to insufficient power. We conclude that
      SLC12A8 is a susceptibility locus for PsV. In order to establish the exact nature
      of this association, efforts to identify the disease-causing variants are
      ongoing.

PMID- 16297190
TI  - Clinical and genetic heterogeneity of erythrokeratoderma variabilis.
AB  - The skin disease erythrokeratoderma variabilis (EKV) has been shown to be
      associated with mutations in GJB3 and GJB4 encoding connexin (Cx)31 and Cx30.3,
      respectively. Gap junctions composed of Cx proteins are intracellular channels
      providing a mechanism of synchronized cellular response facilitating metabolic
      and electronic functions of the cell. In the skin, Cx31 and Cx30.3 are expressed
      in the stratum granulosum of the epidermis with a suggested role in late
      keratinocyte differentiation. Molecular investigations of GJB3 and GJB4 were
      performed in five pedigrees and three sporadic cases of EKV. Mutational analyzes
      revealed disease-associated Cx31 or Cx30.3 mutations in only three probands of
      which two were novel mutations and one was a recurrent mutation. These genetic
      studies further demonstrate the heterogeneous nature of the erythrokeratodermas
      as not all individuals that were clinically diagnosed with EKV harbor Cx31 or
      Cx30.3 mutations.

PMID- 16297191
TI  - The region of 150 kb telometic to HLA-C is associated with psoriasis in the
      Jewish population.
AB  - The HLA-Cw*0602 has been associated with psoriasis in different ethnic groups.
      But, it remains unclear whether HLA-C is the PSORS1 gene (the psoriasis gene in
      the MHC). Thus, several case-control studies have been performed in order to
      investigate whether HLA-C itself determines the susceptibility to the disease. We
      studied 59 Jewish patients with type I psoriasis and 79 matched controls.
      Polymorphic genes and markers from HLA-B (centromeric to HLA-C) to the
      corneodesmosin (CDSN) gene (telomeric to HLA-C) were genotyped in order to
      determine their contribution to the susceptibility to psoriasis. Neither HLA
      Cw*0602 nor the allele CDSN*TTC were significantly associated with psoriasis with
      the size of the sample studied. The genes and markers telomeric to HLA-C such as
      the microsatellite C1_4_4 (OR = 2.6, 95% CI = 1.4-4.7, p(c) = 0.018) the octamer
      transcription factor (OTF)-3 gene (OR = 2.6, 95% CI = 1.6-4.3, p(c) = 0.0001) and
      the alpha-helix coiled-coil rod homologue (HCR) gene (OR = 2.5, 95% CI = 1.3-4.5,
      p(c) = 0.004), however, were associated with the disease. These results suggest
      that a major psoriasis susceptibility gene is likely to be located within a
      region of 150 kb telomeric to HLA-C and centromeric to the CDSN gene.

PMID- 16297189
TI  - Homozygous and compound heterozygous mutations in ZMPSTE24 cause the laminopathy
      restrictive dermopathy.
AB  - Restrictive dermopathy (RD) is a lethal human genetic disorder characterized by
      very tight, thin, easily eroded skin, rocker bottom feet, and joint contractures.
      This disease was recently reported to be associated with a single heterozygous
      mutation in ZMPSTE24 and hypothesized to be a digenic disorder (Navarro et al,
      Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify
      restrictive dermopathy as a lethal neonatal laminopathy. Hum Mol Genet 13:2493
      2503, 2004). ZMPSTE24 encodes an enzyme necessary for the correct processing and
      maturation of lamin A, an intermediate filament component of the nuclear
      envelope. Here we present four unrelated patients with homozygous mutations in
      ZMPSTE24 and a fifth patient with compound heterozygous mutations in ZMPSTE24.
      Two of the three different mutations we found are novel, and all are single base
      insertions that result in messenger RNA frameshifts. As a consequence of the
      presumed lack of ZMPSTE24 activity, prelamin A, the unprocessed toxic form of
      lamin A, was detected in the nuclei of both cultured cells and tissue from RD
      patients, but not in control nuclei. Abnormally aggregated lamin A/C was also
      observed. These results indicate that RD is an autosomal recessive laminopathy
      caused by inactivating ZMPSTE24 mutations that result in defective processing and
      nuclear accumulation of prelamin A.

PMID- 16297192
TI  - ATP2C1 gene mutation analysis in Italian patients with Hailey-Hailey disease.
AB  - Hailey-Hailey disease (HHD) is a rare autosomal dominant disorder characterized
      by recurrent skin lesions predominantly involving the body folds. It is caused by
      heterozygous mutations in the ATP2C1 gene, encoding the human secretory pathway
      Ca2+/Mn2+-ATPase protein 1 (hSPCA1). In this report we describe the molecular
      studies performed in eight HHD cases from Italy that led us to identify six
      different mutations scattered through the ATP2C1 gene in seven of eight cases.
      Four of the detected mutations were novel. Our results confirm the high allelic
      heterogeneity of the ATP2C1 gene and support the notion that HHD is a genetically
      homogeneous disorder. Furthermore, we created a table summarizing all previously
      reported ATP2C1 mutations, adapting the nomenclature, if needed, according to the
      guidelines of the Human Genome Variation Society.

PMID- 16297193
TI  - Increased sensitivity to interferon-alpha in psoriatic T cells.
AB  - Psoriasis is a chronic inflammatory skin disease characterized by abnormal
      epidermal proliferation. Several studies have shown that skin-infiltrating
      activated T cells and cytokines play a pivotal role during the initiation and
      maintenance of the disease. Interferon (IFN)-alpha plays an important role in
      host defense against infections, but recent data have also implicated IFN-alpha
      in psoriasis. Thus, IFN-alpha induces or aggravates psoriasis in some patients,
      and mice lacking a transcriptional attenuator of IFN-alpha/beta signaling
      spontaneously develop a psoriasis-like inflammatory skin disease characterized by
      CD8(+)-infiltrating T cells. In this study, we therefore investigate IFN-alpha
      signaling in T cells isolated from involved skin of psoriatic patients. We show
      that psoriatic T cells have increased and prolonged responses to IFN-alpha, on
      the level of signal transducers and activators of transcription (STAT)
      activation, compared with infiltrating T cells from skin of non-psoriatic donors.
      Functionally, the increased IFN-alpha signaling leads to an increased binding of
      STAT4 to the IFN-gamma promotor, IFN-gamma production, and inhibition of T cell
      growth. In contrast, to STAT responses to other cytokines were not changed in
      psoriasis. In conclusion, we provide evidence that psoriatic T cells have an
      increased sensitivity to IFN-alpha. Thus, our data suggest that increased IFN
      alpha signaling is involved in the pathogenesis of psoriasis.

PMID- 16297194
TI  - Reduced expression of interleukin-2 decreases the frequency of alopecia areata
      onset in C3H/HeJ mice.
AB  - Alopecia areata (AA) is an autoimmune hair loss disease, that can be transferred
      between C3H/HeJ mice by skin grafting. We explored whether AA susceptibility is
      influenced by the availability of interleukin (IL)-2, a cytokine with leukocyte
      activating and regulatory properties. Mice heterozygous for a targeted deletion
      of IL-2 from the histocompatible C3.129P2(B6)-Il2(tm1Hor) substrain, that produce
      reduced levels of IL-2, were examined for AA development after grafting skin from
      AA-affected C3H/HeJ mice. After grafting, nine of 19 (47%) heterozygous IL-2+/
      versus 16 of 18 (88%) IL-2+/+ wild-type littermates developed AA. Although dense
      follicular leukocyte infiltrates were apparent in AA affected wild-type mice, AA
      developing IL-2+/- littermates had a reduced leukocyte infiltration, and AA
      resistant IL-2+/- mice had no inflammation. Lymph node cell analysis revealed a
      reduction in leukocyte activation markers in AA-developing IL-2+/- mice. IL-2+/-
      mice presented with low level expression of cytokines (IL-4, IL-10, interferon
      gamma, transforming growth factor-beta), upregulation of tumor necrosis factor
      receptors, and increased leukocyte apoptosis susceptibility independent of AA
      expression. In the skin, CD4+ cells and monocytes were reduced; activation
      markers were not upregulated and very few CD44v3+ or CD44v10+ leukocytes were
      recovered. Taken together, our data suggest that AA resistance of IL-2+/- mice is
      because of the failure of activated leukocyte recruitment, thus pointing toward
      an involvement of IL-2 in AA pathogenesis.

PMID- 16297195
TI  - Corticotropin-releasing hormone receptor-1 and histidine decarboxylase expression
      in chronic urticaria.
AB  - Certain skin disorders, such as contact dermatitis and chronic urticaria, are
      characterized by inflammation involving mast cells and worsen by stress. The
      underlying mechanism of this effect, however, is not known. The skin appears to
      have the equivalent of a hypothalamic-pituitary-adrenal (HPA) axis, including
      local expression of corticotropin-releasing hormone (CRH) and its receptors (CRH
      R). We have reported that acute stress and intradermal administration of CRH
      stimulate skin mast cells and increase vascular permeability through CRH-R1
      activation. In this study, we investigated the expression of CRH-R1, the main CRH
      R subtype in human skin, and the mast cell related gene histidine decarboxylase
      (HDC), which regulates the production of histamine, in normal and pathological
      skin biopsies. Quantitative real time PCR revealed that chronic urticaria
      expresses high levels of CRH-R1 and HDC as compared to normal foreskin, breast
      skin and cultured human keratinocytes. The lichen simplex samples had high
      expression of CRH-R1, but low HDC. These results implicate CRH-R in chronic
      urticaria, which is often exacerbated by stress.

PMID- 16297196
TI  - Mosquito salivary gland extracts induce EBV-infected NK cell oncogenesis via CD4
      T cells in patients with hypersensitivity to mosquito bites.
AB  - Severe hypersensitivity to mosquito bites (HMB) is characterized by intense local
      skin reactions and systemic symptoms such as high fever, lymphadenopathy, and
      hepatosplenomegaly. Patients with HMB often have natural killer (NK) cell
      lymphocytosis associated with Epstein-Barr virus (EBV) infection. Here we
      investigated whether mosquito bites have any influence on the oncogenesis of EBV
      infected NK cells. We examined six HMB patients with EBV-infected NK cell
      lymphocytosis. We first demonstrated that CD4+ T cells, but not NK cells,
      proliferated well in response to mosquito salivary gland extracts (SGE),
      especially to SGE of Aedes albopictus. When NK cells were cocultured with
      autologous CD4+ T cells stimulated by mosquito SGE, the expression of viral
      oncogene latent membrane protein 1 (LMP1) was remarkably enhanced. Next, we
      stimulated mononuclear cells of the patients with mosquito SGE, and NK cell
      counts were monitored for 28 d. The counts changed little from initial levels in
      the culture with mosquito SGE, whereas they decreased steadily in the culture
      without the extracts. Furthermore, we detected LMP1 mRNA in the skin lesion
      induced by mosquito SGE. These results suggest that mosquito bites can induce
      expression of the viral oncogene LMP1 in NK cells via mosquito antigen-specific
      CD4+ T cells, which is involved in the oncogenesis of NK cells in vivo.

PMID- 16297198
TI  - Junctional adhesion molecules (JAM)-B and -C contribute to leukocyte
      extravasation to the skin and mediate cutaneous inflammation.
AB  - Leukocyte extravasation is a finely tuned process, in which transmigration is the
      final step. Transmigration depends on molecules located at borders of endothelial
      cells; e.g., junctional adhesion molecules (JAM-A, -B and -C). In vivo blockade
      of JAM-A lead to decreased migration of monocytes into the skin. In contrast, the
      role of JAM-B and -C in development of cutaneous inflammation is unknown. We
      therefore elicited an allergic contact dermatitis in mice using 2,4-dinitro-1
      fluorobenzene. RT-PCR and immunofluorescent staining of healthy skin revealed a
      constitutive JAM-B (66.4%+/-6.7% of all vessels) and -C expression (88.6+/
      13.2%), which remained constant after induction of contact dermatitis. Functional
      studies, in which either JAM-B or -C neutralizing antibodies were injected into
      sensitized mice prior to allergen challenge showed a concentration-dependent
      reduction of the contact dermatitis. Decreased ear swelling was accompanied by
      reduction of leukocyte infiltration as analyzed by hematoxylin and eosin (H&E)
      histology and enzyme activity. Combined antibody treatment at doses of 1.25 mg
      per kg bodyweight lead to additive inhibition of allergic contact dermatitis,
      indicating that JAM-B and -C may have distinct functions. In conclusion,
      interactions with JAM-B and -C are essential for development of cutaneous
      inflammation.

PMID- 16297197
TI  - Cutaneous, but not airway, latex exposure induces allergic lung inflammation and
      airway hyperreactivity in mice.
AB  - As respiratory symptoms are common in addition to skin reactions in natural
      rubber latex allergy, we investigated the significance of different allergen
      exposure routes in the development of lung inflammation and airway
      hyperreactivity (AHR). Both intracutaneous (IC) and intraperitoneal (IP) exposure
      followed by airway challenge with latex proteins induced an influx of mononuclear
      cells and eosinophils to the lungs. AHR and lung mucus production increased
      significantly after IC and IP but not after intranasal (IN) exposure.
      Infiltration of inflammatory cells was associated with the induction of T-helper
      type 2 (Th2) cytokines and several CC chemokines. Only a marginal induction of
      these mediators was found after IN exposure. On the contrary, increased levels of
      transforming growth factor-beta1 and forkhead box 3 mRNA, markers of regulatory
      activities, were found in the lungs after IN but not after IC exposure. Finally,
      IC and IP, but not IN, latex exposure induced a striking increase in specific
      immunoglobulin E (IgE) levels. Cutaneous latex exposure in the absence of
      adjuvant followed by airway challenge induces a local Th2-dominated lung
      inflammation and a systemic IgE response. Cutaneous exposure to proteins eluting
      from latex products may therefore profoundly contribute to the development of
      asthma in latex allergy.

PMID- 16297199
TI  - Staphylococcus aureus clonal dynamics and virulence factors in children with
      atopic dermatitis.
AB  - A prospective cohort study was undertaken to determine the clonal dynamics of
      Staphylococcus aureus colonization and infection during 1 y in children with
      atopic dermatitis, and to correlate specific clones, accessory gene regulator
      (agr) groups, and production of virulence factors with eczema activity. Eleven
      children were examined every 6 wk with swaps taken from active eczema, anterior
      nose, axillae and perineum, and scoring of eczema activity by severity scoring of
      atopic dermatitis (SCORAD). Individual S. aureus clonal types were identified and
      examined for production of superantigens, toxins, and were assigned to agr
      groups. S. aureus colonization patterns ranged from rare colonization over
      transient colonization to persistent colonization by a single clone or a dynamic
      exchange of up to five clones. Production of no single virulence factor including
      superantigens and toxins was significantly associated with exacerbation of
      eczema. In four children there was a shift between visits in agr group of
      colonizing clones. These shifts were associated with an increased SCORAD value of
      19 (SE = 7, p = 0.009). Change of clones belonging to the same agr group was not
      associated with a higher SCORAD value. In 11 of 12 cases with two different
      clones co-colonizing a child the clones belonged to the same agr group. In
      conclusion, this limited group of children with atopic dermatitis showed highly
      variable colonization patterns of S. aureus, and communication between strains by
      use of agr encoded octa peptides appeared to be active in vivo. Increased
      severity of eczema was related to a change in agr group and may have been because
      of inflammation triggered by the takeover of an antigenically different clone, as
      agr groups represent ancient phylogenetic lineages.

PMID- 16297200
TI  - Mouse lymphoid tissue contains distinct subsets of langerin/CD207 dendritic
      cells, only one of which represents epidermal-derived Langerhans cells.
AB  - Langerin/CD207 is a C-type lectin associated with formation of Birbeck granules
      (BG) in Langerhans cells (LC). Here, we describe a monoclonal antibody (mAb
      205C1) recognizing the extracellular domain of mouse langerin. Cell-surface
      langerin was detected in all epidermal LC, which presented a uniform phenotype.
      Two subpopulations of langerin+ cells were identified in peripheral lymph nodes
      (LN). One population (subset 1) was CD11c(low/+)/CD8alpha(
      /low)/CD11b+/CD40+/CD86+. The other population (subset 2) was
      CD11c(high)/CD8alpha+/CD11b(low), and lacked CD40 and CD86. Only subset 1 was
      fluorescein 5-isothiocyanate (FITC+) following painting onto epidermis, and the
      appearance of such FITC+ cells in draining LN was inhibited by pertussis toxin.
      Mesenteric LN, spleen, and thymus contained only a single population of langerin+
      DC, corresponding to peripheral LN subset 2. Unexpectedly, BG were absent from
      spleen CD8alpha+ DC despite expression of langerin, and these organelles were not
      induced by mAb 205C1. Collectively, we demonstrate that two langerin+ DC
      populations (subsets 1 and 2) co-exist in mouse lymphoid tissue. Subset 1
      unequivocally identifies epidermal LC-derived DC. The distribution of subset 2
      indicates a non-LC origin of these langerin+ cells. These findings should
      facilitate our understanding of the role played by langerin in lymphoid organ DC
      subsets.

PMID- 16297202
TI  - Role of tetraspanins CD9 and CD151 in primary melanocyte motility.
AB  - Tetraspanins CD9 and CD151 have been implicated in cellular motility and
      intercellular adhesion in several cellular types. Here, we have studied the
      subcellular localization and the functional role of these molecules in primary
      melanocytes. We found that endogenous tetraspanins preferentially clustered in
      areas of melanocyte homotypic intercellular contacts and at the tips of
      dendrites. These observations were further confirmed using time-lapse
      fluorescence confocal microscopy of melanocytes transfected with CD9- and CD151
      GFP (green fluorescent protein) constructs, suggesting an involvement of these
      proteins in cellular contacts and migration. Cell adhesion and migration assays
      performed using blocking monoclonal antibodies against CD9 and CD151 showed no
      significant effect on cell-extracellular matrix adhesion, whereas the migration
      of melanocytes was significantly enhanced. The regulation of the migratory
      capacity of melanocytes by CD9 and CD151 was further confirmed knocking down the
      endogenous expression of these tetraspanins with small interference RNA
      oligonucleotides. Therefore, tetraspanin molecules are localized at motile
      structures in primary human melanocytes regulating the migratory capacity of
      these cells.

PMID- 16297201
TI  - Molecular cloning and expression of human keratinocyte proline-rich protein
      (hKPRP), an epidermal marker isolated from calcium-induced differentiating
      keratinocytes.
AB  - We isolated a human gene encoding keratinocyte proline-rich protein (hKPRP).
      hKPRP gene is located in the region of epidermal differentiation complex on
      chromosome 1q21, and its approximately 2.5 kb mRNA encodes 579 amino acid protein
      with high proline content (18%). The mRNA level of hKPRP was markedly increased
      at both 7 and 14 d after treatment with 1.2 mM calcium in cultured normal human
      epidermal keratinocytes. In situ hybridization demonstrated that hKPRP was
      expressed in upper granular layer of normal epidermis with characteristic
      intermittent pattern. In psoriatic lesion, hKPRP expression was increased as
      compared with normal skin and showed continuous pattern. Immunohistochemical
      analysis also confirmed the expression of hKPRP at the protein level. Western
      blot analysis showed that hKPRP protein of approximately 70 kDa size was
      significantly increased by calcium in a time-dependent manner. In mouse tissue
      blot assays, the expression of KPRP was detected in stomach and skin tissues, and
      began at 17.5 embryonic days. Additionally, hKPRP expression was detected in the
      periderm of human fetal skin from 16 wk estimated gestational age. Together,
      these results suggest that hKPRP is an epidermal marker expressed in stratified
      squamous epithelia and has a potential role in keratinocytes differentiation.

PMID- 16297203
TI  - Efficient TRAIL-R1/DR4-mediated apoptosis in melanoma cells by tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL).
AB  - Therapy resistance is crucial for the high mortality of melanoma. The death
      ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) bears high
      potential as a new anticancer agent, as binding to the death receptors TRAIL
      receptor 1/death receptor 4 (TRAIL-R1/DR4) or TRAIL receptor 2/death receptor 5
      (TRAIL-R2/DR5) triggers apoptosis in most cancer cells. For melanoma, however,
      only a weak responsiveness of primary cultures was reported, and in particular
      the role of DR4 was neglected. For evaluating melanoma susceptibility, we studied
      the functionality of DR4 and DR5 in melanoma cells as well as their expression in
      vivo. DR5 was consistently expressed in melanoma cell lines, whereas DR4 was
      found in only 2/7 cell lines. High sensitivity to TRAIL-induced apoptosis was
      characteristic for DR4-positive melanoma cells, whereas DR4-negative cells showed
      less and delayed response or were resistant. The use of selective DR4/DR5
      blocking antibodies unequivocally proved the prevalent role of DR4 in those
      melanoma cells, where it was expressed. The significance of these data for the in
      vivo situation was finally evaluated by immunohistochemistry, which proved
      pronounced expression of DR4 as well as of DR5 in melanoma primary tumors. Thus,
      DR4 expression in vivo and the high efficiency of DR4-mediated apoptosis may
      suggest reassessment of the suitability of TRAIL and especially of DR4-based
      strategies for melanoma treatment.

PMID- 16297205
TI  - A low UVB dose, with the potential to trigger a protective p53-dependent gene
      program, increases the resilience of keratinocytes against future UVB insults.
AB  - One protein central in the response of human keratinocytes to ultraviolet B
      damage is p53. By transactivating genes involved in either cell cycle arrest or
      DNA repair, p53 has a leading role in the recovery from this damage. Considering
      this role, we wished to investigate whether the triggering of a p53-dependent
      gene program by repetitive ultraviolet B (UVB) exposure can induce an adaptive
      response in human skin cells. In particular, we examined two p53-target genes,
      p21/WAF1 and p53R2, with a crucial role in p53-induced cell cycle arrest and p53
      induced DNA repair respectively. Exposure to a mild UVB dose was able to induce
      an adaptive response in human keratinocytes, leading to increased survival of
      cells that maintain their capacity to repair DNA damage upon exposure to
      apoptotic doses of UVB. Our study indicates that this adaptation response is only
      achieved if the interval between subsequent UVB insults allows sufficient time
      for the p53-induced protective gene program to be induced. Our results also
      demonstrate that small but quickly recurring UVB exposures are as harmful as one
      intense, continual exposure to UVB irradiation. Future research will be oriented
      toward investigating alternative ways to induce an adaptive response without pre
      exposing the cells to UV.

PMID- 16297204
TI  - Calcineurin inhibitors decrease DNA repair and apoptosis in human keratinocytes
      following ultraviolet B irradiation.
AB  - The use of calcineurin inhibitors in solid organ transplantation results in an
      increased risk of skin cancer. We examined the effect of these drugs on DNA
      repair in normal human keratinocytes after ultraviolet B (UVB) irradiation. We
      found that both cyclosporine A (CsA) and ascomycin inhibited removal of
      cyclobutane pyrimidine dimers, and that they also inhibited UVB-induced
      apoptosis. We also observed that UVB induced nuclear localization of the
      transcription factor nuclear factor of activated T-cells (NFAT), and that this
      was blocked by CsA and ascomycin. These data suggest that the increased risk of
      skin cancer observed in organ-transplant patients may be as a result of not only
      systemic immune suppression but also the local inhibition of DNA repair and
      apoptosis in skin by calcineurin inhibitors. These findings may have implications
      for the use of topical calcineurin inhibitors in sun-exposed skin and eyes.

PMID- 16297206
TI  - UVA radiation impairs phenotypic and functional maturation of human dermal
      dendritic cells.
AB  - There is now strong evidence that the ultraviolet A (UVA) part of the solar
      spectrum contributes to the development of skin cancers. Its effect on the skin
      immune system, however, has not been fully investigated. Here, we analyzed the
      effects of UVA radiation on dermal dendritic cells (DDC), which, in addition,
      provided further characterization of these cells. Dermal sheets were obtained
      from normal human skin and irradiated, or not, with UVA at 2 or 12 J per cm2.
      After a 2 d incubation, the phenotype of emigrant cells was analyzed by double
      immunostaining and flow cytometry. Results showed that migratory DDC were best
      characterized by CD1c expression and that only few cells co-expressed the
      Langerhans cell marker Langerin. Whereas the DC extracted from the dermis
      displayed an immature phenotype, emigrant DDC showed increased expression of HLA
      DR and acquired co-stimulation and maturation markers. We showed here that UVA
      significantly decreased the number of viable emigrant DDC, a process related to
      increased apoptosis. Furthermore, UVA irradiation impaired the phenotypic and
      functional maturation of migrating DDC into potent antigen-presenting cells, in a
      concentration-dependent manner. The results provide further evidence that UVA are
      immunosuppressive and suggest an additional mechanism by which solar radiation
      impairs immune response.

PMID- 16297207
TI  - Influence of light exposure on the kinetics of protoporphyrin IX formation in
      normal skin of hairless mice after application of 5-aminolevulinic acid methyl
      ester.
AB  - The rates of protoporphyrin IX (PpIX) photodegradation and reappearance after
      light exposure at 420 and 632 nm were measured in mouse skin at different times
      after 1 h topical application of 5-aminolevulinic acid methyl ester (ALA-Me).
      After ALA-Me application (1 h) and removal, the fluorescence of PpIX increased
      for about 1 h, and then reached a maximum and started to decrease. Reappearance
      of PpIX fluorescence after exposures (degrading 60%-80% of the PpIX) was faster
      for exposures 0.5 h after ALA-Me application than for exposures 3 h. The
      bleaching rate was largest in the former case. This indicates that PpIX is
      located deeper in the skin after 3 h than after 0.5 h, whereas the pool of ALA-Me
      in the skin is largest at 0.5 h. In all cases, the reappearance was faster at a
      skin temperature of 35 degrees C than at 23 degrees C. Reappearance of PpIX
      fluorescence was faster after exposure to light at 420 nm than at 632 nm. The
      rate of elimination of PpIX from the volume of detection was faster after 420 nm
      light irradiation than that after 632 nm. These findings are discussed in view of
      penetration depths of light and ALA-Me, and diffusion of PpIX.

PMID- 16297208
TI  - Selective induction of apoptosis by histone deacetylase inhibitor SAHA in
      cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action.
AB  - Suberoylanilide hydroxamic acid (SAHA), an orally administered inhibitor of
      histone deacetylases, is currently in phase II clinical trials for cutaneous T
      cell lymphomas (CTCL), but the mechanism of SAHA action is unknown. In this
      study, we investigated the anti-tumor effects of SAHA in CTCL cell lines and
      freshly isolated peripheral blood lymphocytes (PBL) from CTCL patients with high
      percentage of circulating malignant T cells. Three cell lines (MJ, Hut78, and HH)
      and PBL from 11 patients and three healthy donors were treated with SAHA (1, 2.5,
      and 5 microM) for 24 and/or 48 h. Apoptosis was determined by flow cytometry
      analysis of sub-G1 hypodiploid nuclei and/or annexin V binding populations.
      Acetylated histones and apoptosis-associated proteins were detected by Western
      blotting. SAHA at 1-5 microM for 24 and 48 h induced apoptosis in a concentration
      and time-dependent manner in three cell lines: MJ (0%-7% and 1%-32%), Hut78 (4%
      36% and 5%-54%), and HH (4%-67% and 8%-81%). SAHA at 1-5 muM for 48 h also
      induced more apoptosis of patients' PBL than healthy donors' (15%-32%versus 6%
      13%, p < 0.05). SAHA treatment caused an accumulation of acetylated histones
      (H2B, H3, and H4), an increase of p21(WAF1) and bax proteins, a decrease of Stat6
      and phospho-Stat6 proteins, and activation of caspase-3 in CTCL cells. Our data
      suggest that selective induction of malignant T cell apoptosis and modulation of
      acetylated histones, p21(WAF1), bax, Stat6, and caspase-3 may underlie the
      therapeutic action of SAHA in CTCL patients.

PMID- 16297209
TI  - The sex steroid precursor DHEA accelerates cutaneous wound healing via the
      estrogen receptors.
AB  - Age-related impaired wound healing states lead to substantial morbidity and cost,
      with treatment in the USA resulting in an expenditure of over $9 billion per
      annum. Dehydroepiandrosterone (DHEA) is a ubiquitous adrenal hormone with
      immunomodulatory properties whose levels decline significantly with advanced age
      in humans. Conversion of DHEA locally to downstream steroid hormones leads to
      estrogenic and/or androgenic effects which may be important in age-related skin
      homeostasis, and which would avoid systemic adverse effects related to estrogen.
      We report that systemic DHEA levels are strongly associated with protection
      against chronic venous ulceration in humans. DHEA accelerated impaired healing in
      an impaired healing model (mice rendered hypogonadal) associated with increased
      matrix deposition and dampens the exaggerated inflammatory response. Such effects
      were mediated by local conversion of DHEA to estrogen, acting through the
      estrogen receptor, and vitro studies suggest a direct effect on specific pro
      inflammatory cytokine production by macrophages via mitogen activated kinase
      (MAP) and phosphatidylinositol 3 (PI3) kinase pathways. In addition, we show that
      local injection of DHEA accelerates impaired healing in an ageing mouse colony.
      We suggest that exogenous application of DHEA accelerates impaired wound repair,
      results which may be applicable to the prophylaxis and treatment of human
      impaired wound healing states.

PMID- 16297210
TI  - Artificial barrier repair in wounds by semi-occlusive foils reduced wound
      contraction and enhanced cell migration and reepithelization in mouse skin.
AB  - The repair of the permeability barrier to prevent the entry of harmful substances
      into the body is a goal in wound healing. Semi-occlusive foils, which provide an
      artificial barrier, are commonly used for the treatment of wounds. We examined
      the effects of foils on wound contraction, cell migration, and reepithelization.
      Full-thickness skin wounds in mice were covered with occlusive latex foils or
      semi-occlusive water vapor-permeable hydrocolloid foils for either the entire,
      the first half, or the second half of the wound-healing period. We found that
      application of foils for the entire healing period initially reduced wound
      healing during the first week of treatment, whereas healing was enhanced during
      the second week. Foils were found to reduce wound contraction, but enhanced
      reepithelization during the second week of wound healing because of increased
      proliferation and migration of keratinocytes. These effects were also noted when
      the hydrocolloid foils were applied for the second part of the healing period,
      only. The fully occlusive latex foil led to irritation of the skin, whereas less
      irritation occurred under semi-occlusive conditions. In summary, we found that
      artificial barrier repair with semi-occlusive foils in wounds reduced wound
      contraction and enhanced cell migration and reepithelization without irritation.

PMID- 16297212
TI  - Neonatal ultraviolet radiation exposure is critical for malignant melanoma
      induction in pigmented Tpras transgenic mice.

PMID- 16297211
TI  - UVB upregulates the antimicrobial protein hCAP18 mRNA in human skin.

PMID- 16297213
TI  - A missense mutation in the cadherin interaction site of the desmoglein 4 gene
      underlies localized autosomal recessive hypotrichosis.

PMID- 16297214
TI  - Association analysis of drug metabolizing enzyme gene polymorphisms in AIDS
      patients with cutaneous reactions to sulfonamides.

PMID- 16297216
TI  - Risk analysis for environmental health triage.
AB  - The Homeland Security Act mandates the development of a national, risk-based
      system to support planning for, response to, and recovery from emergency
      situations involving large-scale toxic exposures. To prepare for and manage
      consequences effectively, planners and responders need not only to identify zones
      of potentially elevated individual risk but also to predict expected casualties.
      Emergency response support systems now define "consequences" by mapping areas in
      which toxic chemical concentrations do or may exceed Acute Exposure Guideline
      Levels (AEGLs) or similar guidelines. However, because AEGLs do not estimate
      expected risks, current unqualified claims that such maps support consequence
      management are misleading. Intentionally protective, AEGLs incorporate various
      safety/uncertainty factors depending on the scope and quality of chemical
      specific toxicity data. Some of these factors are irrelevant, and others need to
      be modified, whenever resource constraints or exposure-scenario complexities
      require responders to make critical trade-off (triage) decisions in order to
      minimize expected casualties. AEGL-exceedance zones cannot consistently be
      aggregated, compared, or used to calculate expected casualties and so may
      seriously misguide emergency response triage decisions. Methods and tools well
      established and readily available to support environmental health protection are
      not yet developed for chemically-related environmental health triage. Effective
      triage decisions involving chemical risks require a new assessment approach that
      focuses on best estimates of likely casualties, rather than on upper plausible
      bounds of individual risk. If risk-based consequence management is to become a
      reality, federal agencies tasked with supporting emergency response must actively
      coordinate to foster new methods that can support effective environmental health
      triage.

PMID- 16297217
TI  - A probabilistic transmission dynamic model to assess indoor airborne infection
      risks.
AB  - The purpose of this article is to quantify the public health risk associated with
      inhalation of indoor airborne infection based on a probabilistic transmission
      dynamic modeling approach. We used the Wells-Riley mathematical model to estimate
      (1) the CO2 exposure concentrations in indoor environments where cases of
      inhalation airborne infection occurred based on reported epidemiological data and
      epidemic curves for influenza and severe acute respiratory syndrome (SARS), (2)
      the basic reproductive number, R0 (i.e., expected number of secondary cases on
      the introduction of a single infected individual in a completely susceptible
      population) and its variability in a shared indoor airspace, and (3) the risk for
      infection in various scenarios of exposure in a susceptible population for a
      range of R0. We also employ a standard susceptible-infectious-recovered (SIR)
      structure to relate Wells-Riley model derived R0 to a transmission parameter to
      implicate the relationships between indoor carbon dioxide concentration and
      contact rate. We estimate that a single case of SARS will infect 2.6 secondary
      cases on average in a population from nosocomial transmission, whereas less than
      1 secondary infection was generated per case among school children. We also
      obtained an estimate of the basic reproductive number for influenza in a
      commercial airliner: the median value is 10.4. We suggest that improving the
      building air cleaning rate to lower the critical rebreathed fraction of indoor
      air can decrease transmission rate. Here, we show that virulence of the organism
      factors, infectious quantum generation rates (quanta/s by an infected person),
      and host factors determine the risk for inhalation of indoor airborne infection.

PMID- 16297218
TI  - How much uncertainty is too much and how do we know? A case example of the
      assessment of ozone monitor network options.
AB  - Limited time and resources usually characterize environmental decision making at
      policy organizations such as the U.S. Environmental Protection Agency. In these
      climates, addressing uncertainty, usually considered a flaw in scientific
      analyses, is often avoided. However, ignoring uncertainties can result in
      unpleasant policy surprises. Furthermore, it is important for decisionmakers to
      know how defensible a chosen policy option is over other options when the
      uncertainties of the data are considered. The purpose of this article is to
      suggest an approach that is unique from other approaches in that it considers
      uncertainty in two specific ways-the uncertainty of stakeholder values within a
      particular decision context and data uncertainty in the light of the decision
      contextual data-values relationship. It is the premise of this article that the
      interaction between data and stakeholder values is critical to how the decision
      options are viewed and determines the effect of data uncertainty on the relative
      acceptability of the decision options, making the understanding of this
      interaction important to decisionmakers and other stakeholders. This approach
      utilizes the recently developed decision analysis framework and process, multi
      criteria integrated resource assessment (MIRA). This article will specifically
      address how MIRA can be used to help decisionmakers better understand the
      importance of uncertainty on the specific (i.e., decision contextual)
      environmental policy options that they are deliberating.

PMID- 16297219
TI  - A risk analysis model of the relationship between beverage consumption from
      school vending machines and risk of adolescent overweight.
AB  - Risk analysis is a widely used tool to understand problems in food safety policy,
      but it is seldom applied to nutrition policy. We propose that risk analysis be
      applied more often to inform debates on nutrition policy, and we conduct a risk
      assessment of the relationship of regular carbonated soft drink (RCSD)
      consumption in schools and body mass index (BMI) as a case study. Data for RCSD
      consumption in schools were drawn from three data sets: the Continuing Survey of
      Food Intake by Individuals 1994-1996, 1998 (CSFII), the National Health and
      Nutrition Examination Survey 1999-2000 (NHANES), and the National Family Opinion
      (NFO) WorldGroup Share of Intake Panel (SIP) study. We used the largest
      relationship between RCSD and BMI that was published by prospective observational
      studies to characterize the maximum plausible relationship in our study.
      Consumption of RCSD in schools was low in all three data sets, ranging from 15
      g/day in NFO-SIP to 60 g/day in NHANES. There was no relationship between RCSD
      consumption from all sources and BMI in either the CSFII or the NHANES data. The
      risk assessment showed no impact on BMI by removing RCSD consumption in school.
      These findings suggest that focusing adolescent overweight prevention programs on
      RCSD in schools will not have a significant impact on BMI.

PMID- 16297220
TI  - Influence of distributional shape of substance parameters on exposure model
      output.
AB  - Uncertainty of environmental concentrations is calculated with the regional
      multimedia exposure model of EUSES 1.0 by considering probability input
      distributions for aqueous solubility, vapor pressure, and octanol-water partition
      coefficient, K(ow). Only reliable experimentally determined data are selected
      from available literature for eight reference chemicals representing a wide
      substance property spectrum. Monte Carlo simulations are performed with uniform,
      triangular, and log-normal input distributions to assess the influence of the
      choice of input distribution type on the predicted concentration distributions.
      The impact of input distribution shapes on output variance exceeds the effect on
      the output mean by one order of magnitude. Both are affected by influence and
      uncertainty (i.e., variance) of the input variable as well. Distributional shape
      has no influence when the sensitivity function of the respective parameter is
      perfectly linear. For nonlinear relationships, overlap of probability mass of
      input distribution with influential ranges of the parameter space is important.
      Differences in computed output distribution are greatest when input distributions
      differ in the most influential parameter range.

PMID- 16297221
TI  - Model averaging using the Kullback information criterion in estimating effective
      doses for microbial infection and illness.
AB  - Since the National Food Safety Initiative of 1997, risk assessment has been an
      important issue in food safety areas. Microbial risk assessment is a systematic
      process for describing and quantifying a potential to cause adverse health
      effects associated with exposure to microorganisms. Various dose-response models
      for estimating microbial risks have been investigated. We have considered four
      two-parameter models and four three-parameter models in order to evaluate
      variability among the models for microbial risk assessment using infectivity and
      illness data from studies with human volunteers exposed to a variety of microbial
      pathogens. Model variability is measured in terms of estimated ED01s and ED10s,
      with the view that these effective dose levels correspond to the lower and upper
      limits of the 1% to 10% risk range generally recommended for establishing
      benchmark doses in risk assessment. Parameters of the statistical models are
      estimated using the maximum likelihood method. In this article a weighted average
      of effective dose estimates from eight two- and three-parameter dose-response
      models, with weights determined by the Kullback information criterion, is
      proposed to address model uncertainties in microbial risk assessment. The
      proposed procedures for incorporating model uncertainties and making inferences
      are illustrated with human infection/illness dose-response data sets.

PMID- 16297222
TI  - Forecasting Spanish natural life expectancy.
AB  - Knowledge of trends in life expectancy is of major importance for policy
      planning. It is also a key indicator for assessing future development of life
      insurance products, substantiality of existing retirement schemes, and long-term
      care for the elderly. This article examines the feasibility of decomposing age
      gender-specific accidental and natural mortality rates. We study this
      decomposition by using the Lee and Carter model. In particular, we fit the
      Poisson log-bilinear version of this model proposed by Wilmoth and Brouhns et al.
      to historical (1975-1998) Spanish mortality rates. In addition, by using the
      model introduced by Wilmoth and Valkonen we analyze mortality-gender
      differentials for accidental and natural rates. We present aggregated life
      expectancy forecasts compared with those constructed using nondecomposed
      mortality rates.

PMID- 16297223
TI  - Stochastically modeling Listeria monocytogenes growth in farm tank milk.
AB  - This article presents a Listeria monocytogenes growth model in milk at the farm
      bulk tank stage. The main objective was to judge the feasibility and value to
      risk assessors of introducing a complex model, including a complete thermal
      model, within a microbial quantitative risk assessment scheme. Predictive
      microbiology models are used under varying temperature conditions to predict
      bacterial growth. Input distributions are estimated based on data in the
      literature, when it is available. If not, reasonable assumptions are made for the
      considered context. Previously published results based on a Bayesian analysis of
      growth parameters are used. A Monte Carlo simulation that forecasts bacterial
      growth is the focus of this study. Three scenarios that take account of the
      variability and uncertainty of growth parameters are compared. The effect of a
      sophisticated thermal model taking account of continuous variations in milk
      temperature was tested by comparison with a simplified model where milk
      temperature was considered as constant. Limited multiplication of bacteria within
      the farm bulk tank was modeled. The two principal factors influencing bacterial
      growth were found to be tank thermostat regulation and bacterial population
      growth parameters. The dilution phenomenon due to the introduction of new milk
      was the main factor affecting the final bacterial concentration. The results show
      that a model that assumes constant environmental conditions at an average
      temperature should be acceptable for this process. This work may constitute a
      first step toward exposure assessment for L. monocytogenes in milk. In addition,
      this partly conceptual work provides guidelines for other risk assessments where
      continuous variation of a parameter needs to be taken into account.

PMID- 16297225
TI  - Using choice experiments to assess people's preferences for railway transports of
      hazardous materials.
AB  - This article investigates whether the choice experiment approach can be used to
      assess people's preferences and the determinants of these preferences in order to
      estimate the costs and benefits of different configurations of the transport of
      hazardous materials by rail. Changes in the exposure to hazardous materials that
      people are subjected to are used rather than changes in accident risk. To the
      best knowledge of the author, this has not been done before in a study of
      people's preferences toward hazardous materials. A mail survey, carried out in
      two cities in Sweden, is used to obtain tentative estimates of the willingness to
      pay for a reduction in exposure as well as the willingness to accept an increase
      in exposure. Special attention is given to viability, since the complexity of the
      activity studied, transport of hazardous materials, and the method used pose
      particular challenges. The response rate and tests of validity and consistency
      indicate that this method can be applied. Moreover, the results suggest that
      studies of this kind may provide guidance on changes in the transport of
      hazardous materials, especially because policymakers may influence the attributes
      presented here. Referring to the exposure of hazardous materials highlights the
      importance of providing the respondents with adequate information regarding
      hazardous transports. An important finding is that the amount of background
      information may have some effect on the stated preferences.

PMID- 16297224
TI  - Information specificity and hazard risk potential as moderators of trust
      asymmetry.
AB  - Trust in risk managers appears to be an important antecedent of public acceptance
      for many hazards. However, such trust may be fragile since research suggests that
      negative performance information has a greater impact than positive performance
      information (Slovic, 1993). Closer examination of these findings suggests two
      potential moderators of this valence-related asymmetry-information specificity
      and hazard risk potential. First, we predicted that the asymmetry would be less
      evident for low versus high specificity information (risk management policies vs.
      concrete events). Second, we predicted that it would also be less evident for a
      low- versus high-risk hazard (pharmaceutical vs. nuclear industry). Study 1
      reanalyzed Slovic's original trust asymmetry data for the nuclear industry. In
      line with Prediction 1, trust asymmetry was less evident for policy than event
      related information. Using a new set of items with more clearly defined levels of
      specificity, Study 2 replicated and extended these findings for the high-risk
      hazard (nuclear power). In line with Prediction 2, trust asymmetry was even less
      evident for the low-risk hazard (pharmaceuticals). Positive policies in this
      industry actually had a greater impact on trust than negative ones, in contrast
      to previous findings. Results support an information diagnosticity account of
      earlier findings and suggest that trust in risk managers may be more robust than
      previously believed.

PMID- 16297226
TI  - Precautionary regulation in Europe and the United States: a quantitative
      comparison.
AB  - Much attention has been addressed to the question of whether Europe or the United
      States adopts a more precautionary stance to the regulation of potential
      environmental, health, and safety risks. Some commentators suggest that Europe is
      more risk-averse and precautionary, whereas the United States is seen as more
      risk-taking and optimistic about the prospects for new technology. Others suggest
      that the United States is more precautionary because its regulatory process is
      more legalistic and adversarial, while Europe is more lax and corporatist in its
      regulations. The flip-flop hypothesis claims that the United States was more
      precautionary than Europe in the 1970s and early 1980s, and that Europe has
      become more precautionary since then. We examine the levels and trends in
      regulation of environmental, health, and safety risks since 1970. Unlike previous
      research, which has studied only a small set of prominent cases selected
      nonrandomly, we develop a comprehensive list of almost 3,000 risks and code the
      relative stringency of regulation in Europe and the United States for each of 100
      risks randomly selected from that list for each year from 1970 through 2004. Our
      results suggest that: (a) averaging over risks, there is no significant
      difference in relative precaution over the period, (b) weakly consistent with the
      flip-flop hypothesis, there is some evidence of a modest shift toward greater
      relative precaution of European regulation since about 1990, although (c) there
      is a diversity of trends across risks, of which the most common is no change in
      relative precaution (including cases where Europe and the United States are
      equally precautionary and where Europe or the United States has been consistently
      more precautionary). The overall finding is of a mixed and diverse pattern of
      relative transatlantic precaution over the period.

PMID- 16297227
TI  - Risk perception and technological development at a societal level.
AB  - This article tests the hypothesis that the exposure to the threat to societies
      posed by the introduction of new technologies is associated with a normalization
      of risk perception. Data collected in 2000 by the International Social Survey
      Programme (ISSP) on environmental issues were used to explore this hypothesis.
      Representative samples from 25 countries were employed to assess the national
      levels of perceived threat to the environment associated with a series of
      technologies and activities. These values were correlated with economic
      indicators (mainly from the World Bank) of the diffusion of each of the
      technologies or activities in each country. Results indicate a negative
      association of risk perception with the level of technological prevalence
      (societal normalization effect) and a positive association with the rate of
      growth of the technology (societal sensitivity effect). These results indicate
      that the most acute levels of perceived environmental risk are found in those
      countries where the level of technological prevalence is low but where there has
      recently been substantial technological development. Environmental awareness is a
      mediator of the relationship between risk perception and the indices of
      technological diffusion. This result means that: (1) societal normalization of
      risk is not a direct consequence of prevalence of the technology, but is driven
      by awareness of technological development and that (2) societal sensitivity to
      risk is associated with lower levels of environmental awareness.

PMID- 16297228
TI  - Who does the public trust? The case of genetically modified food in the United
      States.
AB  - Trust is important for the perception of many types of risk, including those
      relating to genetically modified (GM) food. Who the public trusts in any given
      circumstance, however, is not well understood. In this study of public trust
      regarding GM food, an exploratory factor analysis with Promax rotation reveals
      public classification of three common institutional types-evaluators, watchdogs,
      and merchants. The structure of relationships among these stakeholders can act to
      enable or constrain public support for this new technology. Evaluators
      scientists, universities, and medical professionals-are the most trusted.
      Watchdogs-consumer advocacy organizations, environmental organizations, and media
      sources-are moderately trusted. Merchants-grocers and grocery stores, industry,
      and farmers-are least trusted. While the federal government is seen as closest to
      being an evaluator, it is not highly correlated with any of the factors. The lack
      of trust in the organizations with the greatest resources and responsibilities
      for ensuring the safety of GM food should be seen as an important obstacle to the
      adoption of the technology.

PMID- 16297229
TI  - Perception of mobile phone and base station risks.
AB  - Perceptions of risks associated with mobile phones, base stations, and other
      sources of electromagnetic fields (EMF) were examined. Data from a telephone
      survey conducted in the German- and French-speaking parts of Switzerland are
      presented (N = 1,015). Participants assessed both risks and benefits associated
      with nine different sources of EMF. Trust in the authorities regulating these
      hazards was assessed as well. In addition, participants answered a set of
      questions related to attitudes toward EMF and toward mobile phone base stations.
      According to respondents' assessments, high-voltage transmission lines are the
      most risky source of EMF. Mobile phones and mobile phone base stations received
      lower risk ratings. Results showed that trust in authorities was positively
      associated with perceived benefits and negatively associated with perceived
      risks. People who use their mobile phones frequently perceived lower risks and
      higher benefits than people who use their mobile phones infrequently. People who
      believed they lived close to a base station did not significantly differ in their
      level of risks associated with mobile phone base stations from people who did not
      believe they lived close to a base station. Regarding risk regulation, a majority
      of participants were in favor of fixing limiting values based on the worst-case
      scenario. Correlations suggest that belief in paranormal phenomena is related to
      level of perceived risks associated with EMF. Furthermore, people who believed
      that most chemical substances cause cancer also worried more about EMF than
      people who did not believe that chemical substances are that harmful. Practical
      implications of the results are discussed.

PMID- 16297230
TI  - Feeling at risk matters: water managers and the decision to use forecasts.
AB  - Experts contend that weather and climate forecasts could have an important role
      in risk management strategies for community water systems. Yet, most water
      managers make minimal use of these forecasts. This research explores the
      determinants of the use of weather and climate forecasts by surveying managers of
      community water systems in two eastern American states (South Carolina and the
      Susquehanna River Basin of Pennsylvania). Assessments of the reliability of
      weather and climate forecasts are not driving their use as water managers who
      find forecasts reliable are no more likely to use them than are managers who find
      them unreliable. Although larger systems and those depending on surface water are
      more likely to use forecasts for some (but not all) purposes, the strongest
      determinant of forecast use is risk perceptions. Water managers who expect to
      face problems from weather events in the next decade are much more likely to use
      forecasts than are water managers who expect few problems. Their expectations of
      future problems are closely linked with past experience: water managers who have
      had problems with specific types of weather events (e.g., flood emergencies) in
      the last 5 years are likely to expect to experience problems in the next decade.
      Feeling at risk, regardless of the specific source of that weather-related risk,
      stimulates a decision to use weather and climate forecasts.

PMID- 16297232
TI  - Uncertainty analysis for computer model projections of hurricane losses.
AB  - Projecting losses associated with hurricanes is a complex and difficult
      undertaking that is wrought with uncertainties. Hurricane Charley, which struck
      southwest Florida on August 13, 2004, illustrates the uncertainty of forecasting
      damages from these storms. Due to shifts in the track and the rapid
      intensification of the storm, real-time estimates grew from 2 to 3 billion
      dollars in losses late on August 12 to a peak of 50 billion dollars for a brief
      time as the storm appeared to be headed for the Tampa Bay area. The storm hit the
      resort areas of Charlotte Harbor near Punta Gorda and then went on to Orlando in
      the central part of the state, with early poststorm estimates converging on a
      damage estimate in the 28 to 31 billion dollars range. Comparable damage to
      central Florida had not been seen since Hurricane Donna in 1960. The Florida
      Commission on Hurricane Loss Projection Methodology (FCHLPM) has recognized the
      role of computer models in projecting losses from hurricanes. The FCHLPM
      established a professional team to perform onsite (confidential) audits of
      computer models developed by several different companies in the United States
      that seek to have their models approved for use in insurance rate filings in
      Florida. The team's members represent the fields of actuarial science, computer
      science, meteorology, statistics, and wind and structural engineering. An
      important part of the auditing process requires uncertainty and sensitivity
      analyses to be performed with the applicant's proprietary model. To influence
      future such analyses, an uncertainty and sensitivity analysis has been completed
      for loss projections arising from use of a Holland B parameter hurricane wind
      field model. Uncertainty analysis quantifies the expected percentage reduction in
      the uncertainty of wind speed and loss that is attributable to each of the input
      variables.

PMID- 16297231
TI  - Sensitivity analysis for computer model projections of hurricane losses.
AB  - Projecting losses associated with hurricanes is a complex and difficult
      undertaking that is fraught with uncertainties. Hurricane Charley, which struck
      southwest Florida on August 13, 2004, illustrates the uncertainty of forecasting
      damages from these storms. Due to shifts in the track and the rapid
      intensification of the storm, real-time estimates grew from 2 billion dollars to
      3 billion dollars in losses late on the 12th to a peak of 50 billion dollars for
      a brief time as the storm appeared to be headed for the Tampa Bay area. The storm
      struck the resort areas of Charlotte Harbor and moved across the densely
      populated central part of the state, with early poststorm estimates in the 28
      dollars to 31 billion dollars range, and final estimates converging at 15 billion
      dollars as the actual intensity at landfall became apparent. The Florida
      Commission on Hurricane Loss Projection Methodology (FCHLPM) has a great
      appreciation for the role of computer models in projecting losses from
      hurricanes. The FCHLPM contracts with a professional team to perform onsite
      (confidential) audits of computer models developed by several different companies
      in the United States that seek to have their models approved for use in insurance
      rate filings in Florida. The team's members represent the fields of actuarial
      science, computer science, meteorology, statistics, and wind and structural
      engineering. An important part of the auditing process requires uncertainty and
      sensitivity analyses to be performed with the applicant's proprietary model. To
      influence future such analyses, an uncertainty and sensitivity analysis has been
      completed for loss projections arising from use of a sophisticated computer model
      based on the Holland wind field. Sensitivity analyses presented in this article
      utilize standardized regression coefficients to quantify the contribution of the
      computer input variables to the magnitude of the wind speed.

PMID- 16297233
TI  - Functional approximation and optimal specification of the mechanical risk index.
AB  - The mechanical risk index (MRI) is a numerical measure that quantifies the
      complexity of drilling a well. The purpose of this article is to examine the role
      of the component factors of the MRI and its structural and parametric
      assumptions. A meta-modeling methodology is applied to derive functional
      expressions of the MRI, and it is shown that the MRI can be approximated in terms
      of a linear functional. The variation between the MRI measure and its functional
      specification is determined empirically, and for a reasonable design space, the
      functional specification is shown to a good approximating representation. A
      drilling risk index is introduced to quantify the uncertainty in the time and
      cost associated with drilling a well. A general methodology is outlined to create
      an optimal MRI specification.

PMID- 16297234
TI  - Efficacy of sulfadoxine-pyrimethamine in Tanzania after two years as first-line
      drug for uncomplicated malaria: assessment protocol and implication for treatment
      policy strategies.
AB  - BACKGROUND: Systematic surveillance for resistant malaria shows high level of
      resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP) across
      eastern and southern parts of Africa. This study assessed in vivo SP efficacy
      after two years of use as an interim first-line drug in Tanzania, and determined
      the rates of treatment failures obtained after 14 and 28 days of follow-up.
      METHODS: The study was conducted in the Ipinda, Mlimba and Mkuranga health
      facilities in Tanzania. Children aged 6-59 months presenting with raised
      temperature associated exclusively with P. falciparum (1,000-100,000 parasites
      per microl) were treated with standard dose of SP. Treatment responses were
      classified according to the World Health Organization (WHO) definition as
      Adequate Clinical and Parasitological Response (ACPR), Early Treatment Failure
      (ETF), Late Clinical Failure (LCF) and Late Parasitological Failure (LPF) on day
      14 and day 28. RESULTS: Overall 196 (85.2%) of 230 patients had ACPR on day 14
      but only 116 (50.9%) on day 28 (57.7% after excluding new infections by parasite
      genotyping). Altogether 21 (9.1%) and 13 (5.7%) of the 230 patients assessed up
      to day 14 and 39 (17.1%) and 55 (24.1%) of the 228 followed up to day 28 had
      clinical and parasitological failure, respectively. CONCLUSION: These findings
      indicate that SP has low therapeutic value in Tanzania. The recommendation of
      changing first line treatment to artemether + lumefantrine combination therapy
      from early next year is, therefore, highly justified. These findings further
      stress that, for long half-life drugs such as SP, establishment of cut-off points
      for policy change in high transmission areas should consider both clinical and
      parasitological responses beyond day 14.

PMID- 16297235
TI  - Comment on and reply to "Analysis of variation of amplitudes in cell cycle gene
      expression" by Liu, Gaido and Wolfinger: on the analysis of gene expression
      during the normal, eukaryotic, cell cycle.
AB  - BACKGROUND: The paper of Liu, Gaido and Wolfinger on gene expression during the
      division cycle of HeLa cells using the data of Whitfield et al. are discussed in
      order to see whether their analysis is related to gene expression during the
      division cycle. RESULTS: The results of Liu, Gaido and Wolfinger demonstrate that
      different inhibition methods proposed to "synchronize" cells lead to different
      levels of gene expression. This result, in and of itself, should be taken as
      evidence that the original work of Whitfield et al. is flawed and should not be
      used to support the notion that the cells studied were synchronized or that the
      microarray analyses identify cell-cycle-regulated genes. Furthermore, the DNA
      content evidence presented by Whitfield et al. supports the proposal that the
      cells described as 'synchronized' are not synchronized. A comparison of the gene
      expression amplitudes from two different experiments indicates that the results
      are not reproducible. CONCLUSION: It is concluded that the analysis of Liu,
      Gaido, and Wolfinger is problematic because their work assumes that the cells
      they analyze are or were synchronized. The very fact that different inhibition
      methods lead to different degrees of gene expression should be taken as
      additional evidence that the experiments should be viewed skeptically rather than
      accepted as an approach to understanding gene expression during the cell cycle.

PMID- 16297237
TI  - Saline systems of the Great Plains of western Canada: an overview of the
      limnogeology and paleolimnology.
AB  - In much of the northern Great Plains, saline and hypersaline lacustrine brines
      are the only surface waters present. As a group, the lakes of this region are
      unique: there is no other area in the world that can match the concentration and
      diversity of saline lake environments exhibited in the prairie region of Canada
      and northern United States. The immense number of individual salt lakes and
      saline wetlands in this region of North America is staggering. Estimates vary
      from about one million to greater than 10 million, with densities in some areas
      being as high as 120 lakes/km2. Despite over a century of scientific
      investigation of these salt lakes, we have only in the last twenty years advanced
      far enough to appreciate the wide spectrum of lake types, water chemistries, and
      limnological processes that are operating in the modern settings. Hydrochemical
      data are available for about 800 of the lake brines in the region. Composition,
      textural, and geochemical information on the modern bottom sediments has been
      collected for just over 150 of these lakes. Characterization of the biological
      and ecological features of these lakes is based on even fewer investigations, and
      the stratigraphic records of only twenty basins have been examined. The lake
      waters show a considerable range in ionic composition and concentration. Early
      investigators, concentrating on the most saline brines, emphasized a strong
      predominance of Na+ and SO4-2 in the lakes. It is now realized, however, that not
      only is there a complete spectrum of salinities from less than 1 ppt TDS to
      nearly 400 ppt, but also virtually every water chemistry type is represented in
      lakes of the region. With such a vast array of compositions, it is difficult to
      generalize. Nonetheless, the paucity of Cl-rich lakes makes the northern Great
      Plains basins somewhat unusual compared with salt lakes in many other areas of
      the world (e.g., Australia, western United States). Compilations of the lake
      water chemistries show distinct spatial trends and regional variations controlled
      by groundwater input, climate, and geomorphology. Short-term temporal variations
      in the brine composition, which can have significant effects on the composition
      of the modern sediments, have also been well documented in several individual
      basins. From a sedimentological and mineralogical perspective, the wide range of
      water chemistries exhibited by the lakes leads to an unusually large diversity of
      modern sediment composition. Over 40 species of endogenic precipitates and
      authigenic minerals have been identified in the lacustrine sediments. The most
      common non-detrital components of the modern sediments include: calcium and
      calcium-magnesium carbonates (magnesian calcite, aragonite, dolomite), and
      sodium, magnesium, and sodium-magnesium sulfates (mirabilite, thenardite,
      bloedite, epsomite). Many of the basins whose brines have very high Mg/Ca ratios
      also have hydromagnesite, magnesite, and nesquehonite. Unlike salt lakes in many
      other areas of the world, halite, gypsum, and calcite are relatively rare
      endogenic precipitates in the Great Plains lakes. The detrital fraction of the
      lacustrine sediments is normally dominated by clay minerals, carbonate minerals,
      quartz, and feldspars.Sediment accumulation in these salt lakes is controlled and
      modified by a wide variety of physical, chemical, and biological processes.
      Although the details of these modern sedimentary processes can be exceedingly
      complex and difficult to discuss in isolation, in broad terms, the processes
      operating in the salt lakes of the Great Plains are ultimately controlled by
      three basic factors or conditions of the basin: (a) basin morphology; (b) basin
      hydrology; and (c) water salinity and composition. Combinations of these
      parameters interact to control nearly all aspects of modern sedimentation in
      these salt lakes and give rise to four 'end member' types of modern saline
      lacustrine settings in the Great Plains: (a) clastics-dominated playas; (b) salt
      dominated playas; (c) deep water, non-stratified lakes; and (d) deep water,
      "permanently" stratified lakes.

PMID- 16297236
TI  - A gap between acceptance and knowledge of herbal remedies by physicians: the need
      for educational intervention.
AB  - BACKGROUND: The unprecedented global increase in the use of herbal remedies is
      set to continue apace well into the foreseeable future. This raises important
      public health concerns, especially as it relates to safety issues including
      adverse effects and herb-drug interactions. Most Western-trained physicians are
      ignorant of the risks and benefits of this healthcare modality and assessment of
      acceptance and knowledge would identify appropriate intervention strategies to
      improve physician-patient communication in this area. METHODS: A cross-sectional
      survey was done using an interviewer-administered pilot tested de novo
      questionnaire at six public hospitals in Trinidad between May-July 2004. The
      questionnaire utilized weighed questions to quantify acceptance (maximum score =
      14 points) and knowledge (maximum score = 52 points). Acceptance and knowledge
      scores were analyzed using the ANOVA and Tukey's tests. RESULTS: Of 192
      physicians interviewed, most (60.4%) believed that herbal remedies were
      beneficial to health. Respondents had relatively high acceptance levels (mean =
      5.69 +/- 0.29 points or 40% of total possible score) and poor knowledge (mean =
      7.77 +/- 0.56 points or 15% of total possible score). Seventy-eight physicians
      (40.6%) admitted having used herbs in the past, and 60 of these (76.9%) were
      satisfied with the outcome. Although 52 physicians (27.1%) recommended the use of
      herbs to their patients only 29 (15.1%) were able to identify at least one known
      herb-drug interaction. CONCLUSION: The use of herbal remedies is relatively high
      in Trinidad, as throughout the world, and most patients self-medicate with or
      without the knowledge of their attending physician. Surprisingly, we demonstrated
      relatively high acceptance levels and use of herbs among physicians in Trinidad.
      This interesting scenario of high acceptance levels and poor knowledge creates a
      situation that demands urgent intervention. We recommend educational intervention
      to narrow the gap between acceptance and knowledge so that physicians would be
      adequately equipped to communicate with their patients on this modality. The
      integration of herbal medicine into the curriculum of medical schools, continuing
      education programs and the availability of reputable pharmacopoeias for
      referencing at public health institutions are useful instruments that can be used
      to close this gap and promote improved physician-patient communication.

PMID- 16297238
TI  - Formalin injection causes a coordinated spinal cord CO/NO-cGMP signaling system
      response.
AB  - BACKGROUND: The CO/NO-cGMP signalling system participates in the regulation of
      many physiological processes. The roles this system plays in spinal cord
      nociceptive signalling are particularly important. While individual components
      have been examined in isolation, little study has been dedicated to understanding
      the regulation and functioning of the system as a whole. RESULTS: In these
      studies we examined the time course of expression of 13 genes coding for
      components of this system including isoforms of the heme oxygenase (HO), nitric
      oxide synthase (NOS), soluble guanylate cyclase (sGC), cGMP dependent protein
      kinase (PKG) and phosphodiesterase (PDE) enzyme systems. Of the 13 genes studied,
      11 had spinal cord mRNA levels elevated at one or more time points up to 48 hours
      after hindpaw formalin injection. Of the 11 with elevated mRNA, 8 had elevated
      protein levels 48 hours after formalin injection when mechanical allodynia was
      maximal. No component had an increased protein level which did not have an
      increased mRNA level at one or more time points. Injection of morphine 10 mg/kg
      prior to formalin completely abolished the acute nociceptive behaviours, but did
      not alter the degree of sensitivity which developed in the formalin treated hind
      paws during the subsequent 48 hours. Morphine treatment did, however, eliminate
      formalin induced increases in enzyme protein levels. CONCLUSION: Our results
      indicate that the expression of the components of the CO/NO-cGMP signalling
      system seems to be coordinated in such a way that a generalized multi-level
      enhancement rather than a tightly limited step specific response occurs with
      noxious stimulation. Furthermore, the analgesic morphine administered prior to
      noxious stimulation can prevent long-term changes in gene expression though not
      necessarily nociceptive sensitisation.

PMID- 16297240
TI  - A stepwise framework for the normalization of array CGH data.
AB  - BACKGROUND: In two-channel competitive genomic hybridization microarray
      experiments, the ratio of the two fluorescent signal intensities at each spot on
      the microarray is commonly used to infer the relative amounts of the test and
      reference sample DNA levels. This ratio may be influenced by systematic
      measurement effects from non-biological sources that can introduce biases in the
      estimated ratios. These biases should be removed before drawing conclusions about
      the relative levels of DNA. The performance of existing gene expression
      microarray normalization strategies has not been evaluated for removing
      systematic biases encountered in array-based comparative genomic hybridization
      (CGH), which aims to detect single copy gains and losses typically in samples
      with heterogeneous cell populations resulting in only slight shifts in signal
      ratios. The purpose of this work is to establish a framework for correcting the
      systematic sources of variation in high density CGH array images, while
      maintaining the true biological variations. RESULTS: After an investigation of
      the systematic variations in the data from two array CGH platforms, SMRT (Sub
      Mega base Resolution Tiling) BAC arrays and cDNA arrays of Pollack et al., we
      have developed a stepwise normalization framework integrating novel and existing
      normalization methods in order to reduce intensity, spatial, plate and background
      biases. We used stringent measures to quantify the performance of this stepwise
      normalization using data derived from 5 sets of experiments representing self
      self hybridizations, replicated experiments, detection of single copy changes,
      array CGH experiments which mimic cell population heterogeneity, and array CGH
      experiments simulating different levels of gene amplifications and deletions. Our
      results demonstrate that the three-step normalization procedure provides
      significant improvement in the sensitivity of detection of single copy changes
      compared to conventional single step normalization approaches in both SMRT BAC
      array and cDNA array platforms. CONCLUSION: The proposed stepwise normalization
      framework preserves the minute copy number changes while removing the observed
      systematic biases.

PMID- 16297239
TI  - An acquisition account of genomic islands based on genome signature comparisons.
AB  - BACKGROUND: Recent analyses of prokaryotic genome sequences have demonstrated the
      important force horizontal gene transfer constitutes in genome evolution.
      Horizontally acquired sequences are detectable by, among others, their
      dinucleotide composition (genome signature) dissimilarity with the host genome.
      Genomic islands (GIs) comprise important and interesting horizontally transferred
      sequences, but information about acquisition events or relatedness between GIs is
      scarce. In Vibrio vulnificus CMCP6, 10 and 11 GIs have previously been identified
      in the sequenced chromosomes I and II, respectively. We assessed the
      compositional similarity and putative acquisition account of these GIs using the
      genome signature. For this analysis we developed a new algorithm, available as a
      web application. RESULTS: Of 21 GIs, VvI-1 and VvI-10 of chromosome I have
      similar genome signatures, and while artificially divided due to a linear
      annotation, they are adjacent on the circular chromosome and therefore comprise
      one GI. Similarly, GIs VvI-3 and VvI-4 of chromosome I together with the region
      between these two islands are compositionally similar, suggesting that they form
      one GI (making a total of 19 GIs in chromosome I + chromosome II). Cluster
      analysis assigned the 19 GIs to 11 different branches above our conservative
      threshold. This suggests a limited number of compositionally similar donors or
      intragenomic dispersion of ancestral acquisitions. Furthermore, 2 GIs of
      chromosome II cluster with chromosome I, while none of the 19 GIs group with
      chromosome II, suggesting an unidirectional dispersal of large anomalous gene
      clusters from chromosome I to chromosome II. CONCLUSION: From the results, we
      infer 10 compositionally dissimilar donors for 19 GIs in the V. vulnificus CMCP6
      genome, including chromosome I donating to chromosome II. This suggests multiple
      transfer events from individual donor types or from donors with similar genome
      signatures. Applied to other prokaryotes, this approach may elucidate the
      acquisition account in their genome sequences, and facilitate donor
      identification of GIs.

PMID- 16297241
TI  - Genome-wide identification of the regulatory targets of a transcription factor
      using biochemical characterization and computational genomic analysis.
AB  - BACKGROUND: A major challenge in computational genomics is the development of
      methodologies that allow accurate genome-wide prediction of the regulatory
      targets of a transcription factor. We present a method for target identification
      that combines experimental characterization of binding requirements with
      computational genomic analysis. RESULTS: Our method identified potential target
      genes of the transcription factor Ndt80, a key transcriptional regulator involved
      in yeast sporulation, using the combined information of binding affinity,
      positional distribution, and conservation of the binding sites across multiple
      species. We have also developed a mathematical approach to compute the false
      positive rate and the total number of targets in the genome based on the multiple
      selection criteria. CONCLUSION: We have shown that combining biochemical
      characterization and computational genomic analysis leads to accurate
      identification of the genome-wide targets of a transcription factor. The method
      can be extended to other transcription factors and can complement other genomic
      approaches to transcriptional regulation.

PMID- 16297242
TI  - Feed-forward inhibition: a novel cellular mechanism for the analgesic effect of
      substance P.
AB  - Substance P (SP) is a neuropeptide well known for its contribution to pain
      transmission in the spinal cord, however, less is known about the possible
      modulatory effects of SP. A new study by Gu and colleagues, published in
      Molecular Pain (2005, 1:20), describes its potential role in feed-forward
      inhibition in lamina V of the dorsal horn of the spinal cord. This inhibition
      seems to function through a direct excitation of GABAergic interneurons by
      substance P released from primary afferent fibers and has a distinct temporal
      phase of action from the well-described glutamate-dependent feed-forward
      inhibition. It is believed that through this inhibition, substance P can balance
      nociceptive output from the spinal cord.

PMID- 16297244
TI  - Intermittent pneumatic compression for prevention of pulmonary thromboembolism
      after gynecologic surgery.
AB  - BACKGROUND: To investigate the incidence of pulmonary embolism and risk factors
      for this condition after obstetric and gynecologic surgery, as well as the
      efficacy of intermittent pneumatic compression. METHODS: A total of 6,218
      patients operated at Keio University Hospital excluding obstetric or infertility
      related surgery and uterine cervical conization were evaluated retrospectively to
      determine the preventive effect of intermittent pneumatic compression on
      postoperative pulmonary embolism. RESULTS: Pulmonary embolism occurred in 42
      patients (0.68%). Multivariate analysis showed that malignancy, blood
      transfusion, and a body mass index > or =25 kg/m2 or > or =28 kg/m2 were
      independent risk factors for postoperative pulmonary embolism. A significantly
      lower incidence of pulmonary embolism occurred in patients receiving pneumatic
      compression postoperatively versus those without it. Among gynecologic
      malignancies, endometrial cancer was a significant risk factor for pulmonary
      embolism. CONCLUSION: Preventive measures, including intermittent pneumatic
      compression, should be taken to avoid postoperative pulmonary thromboembolism in
      the gynecology field.

PMID- 16297243
TI  - Principal component analysis for predicting transcription-factor binding motifs
      from array-derived data.
AB  - BACKGROUND: The responses to interleukin 1 (IL-1) in human chondrocytes
      constitute a complex regulatory mechanism, where multiple transcription factors
      interact combinatorially to transcription-factor binding motifs (TFBMs). In order
      to select a critical set of TFBMs from genomic DNA information and an array
      derived data, an efficient algorithm to solve a combinatorial optimization
      problem is required. Although computational approaches based on evolutionary
      algorithms are commonly employed, an analytical algorithm would be useful to
      predict TFBMs at nearly no computational cost and evaluate varying modelling
      conditions. Singular value decomposition (SVD) is a powerful method to derive
      primary components of a given matrix. Applying SVD to a promoter matrix defined
      from regulatory DNA sequences, we derived a novel method to predict the critical
      set of TFBMs. RESULTS: The promoter matrix was defined to establish a
      quantitative relationship between the IL-1-driven mRNA alteration and genomic DNA
      sequences of the IL-1 responsive genes. The matrix was decomposed with SVD, and
      the effects of 8 potential TFBMs (5'-CAGGC-3', 5'-CGCCC-3', 5'-CCGCC-3', 5'-ATGGG
      3', 5'-GGGAA-3', 5'-CGTCC-3', 5'-AAAGG-3', and 5'-ACCCA-3') were predicted from a
      pool of 512 random DNA sequences. The prediction included matches to the core
      binding motifs of biologically known TFBMs such as AP2, SP1, EGR1, KROX, GC-BOX,
      ABI4, ETF, E2F, SRF, STAT, IK-1, PPARgamma, STAF, ROAZ, and NFkappaB, and their
      significance was evaluated numerically using Monte Carlo simulation and genetic
      algorithm. CONCLUSION: The described SVD-based prediction is an analytical method
      to provide a set of potential TFBMs involved in transcriptional regulation. The
      results would be useful to evaluate analytically a contribution of individual DNA
      sequences.

PMID- 16297247
TI  - Hearts with isomerism of the right atrial appendages - one of the worst forms of
      disease in 2005.

PMID- 16297245
TI  - How and why community hospital clinicians document a positive screen for intimate
      partner violence: a cross-sectional study.
AB  - BACKGROUND: This two-part study examines primary care clinicians' chart
      documentation and attitudes when confronted by a positive waiting room screen for
      intimate partner violence (IPV). METHODS: Patients at community hospital
      affiliated health centers completed a screening questionnaire in waiting rooms
      that primary care providers (PCPs) were subsequently given at the time of the
      visit. We first reviewed the medical records of patients who screened positive
      for IPV, evaluating the presence and quality of documentation. Next we
      administered a survey to PCPs that measured their knowledge, attitudes and
      practice regarding IPV. RESULTS: Seventy-two percent of charts contained some
      documentation of IPV, however only 10% contained both a referral and safety plan.
      PCPs were more likely to refer patients (p < .05) who screened positively for
      mood or anxiety disorders, disclosed that they feared for their safety or were
      economically disadvantaged. Those that feared for their safety or endorsed mood
      or anxiety disorders were more likely to have notation of a safety plan in their
      records. When surveyed, 81.6% of clinicians strongly agreed that it is their role
      to inquire about IPV, but only 68% expressed confidence in their ability to
      manage it. In contrast, 93% expressed confidence in managing depression. Sixty
      seven percent identified time constraints as a barrier to care. Predictors of PCP
      confidence in treating patients who have experienced IPV (p < .05) included hours
      of recent training and clinical experience with IPV. CONCLUSION: Mandatory
      waiting room screening for IPV does not result in high levels of referral or
      safety planning by PCPs. Despite the implementation of a screening process,
      clinicians lack confidence and time to address IPV in their patient populations
      suggesting that alternative methods of training and supporting PCPs need to be
      developed.

PMID- 16297248
TI  - A new look at acute rheumatic mitral regurgitation.

PMID- 16297249
TI  - Pulmonary arterial angioplasty: heed the message -why bother?

PMID- 16297250
TI  - Limitations and perspectives with the approach to rheumatic fever and rheumatic
      heart disease.

PMID- 16297251
TI  - The role of echocardiography in diagnosing carditis in the setting of acute
      rheumatic fever.
AB  - OBJECTIVES: Acute rheumatic fever and its sequel, rheumatic heart disease, is a
      major problem in children, adolescents and young adults. Despite the widespread
      application of the Jones criterions, carditis is either underdiagnosed or
      overdiagnosed. Echocardiography is rarely used optimally for precise diagnosis.
      The objective of our study, therefore, was to define the potential role of
      echocardiography in detecting carditis in the setting of acute rheumatic fever.
      MATERIALS AND METHODS: We performed echocardiography in 452 consecutive patients
      with acute rheumatic fever, clinically diagnosed by the strict Jones criterions,
      using the patients as part of a multi-centric and double blinded prospective
      study. RESULTS: Of our 452 patients, 230 were males, and 222 were females. The
      youngest was aged 1 year 11 months, while the oldest was a 51-year-old female.
      Out of the 452 cases of acute rheumatic fever, 239 patients (52.8%) had
      arthritis. Out of 164 cases of clinically diagnosed carditis, only 141 cases had
      echocardiographic evidence of carditis (85.97%). The remaining 23 patients (14%)
      had functional murmurs, tachycardia, or anaemia. Of the patients, 2 also had
      congenitally malformed hearts. Of 40 patients with rheumatic chorea, 28 (70%) had
      echocardiographic evidence of carditis or valvitis. Polyarthralgia was seen in
      213 cases (47.12%), from which only 38 patients (17.8%) had carditis clinically,
      albeit that 88 patients (41.3%) showed echocardiographic evidence of subclinical
      carditis or valvitis. CONCLUSION: Echocardiography, when carried out in patients
      with acute rheumatic fever diagnosed strictly according to the Jones criterion,
      can avoid both overdiagnosis and underdiagnosis of carditis. A high incidence of
      carditis, or subclinical carditis, is detected by echocardiography when performed
      in patients with rheumatic chorea or arthralgia.

PMID- 16297252
TI  - An echocardiographic index for decompensation of the chronically volume
      overloaded left ventricle in children.
AB  - AIMS: The criterions for the timing of surgical intervention in children with
      rheumatic mitral or aortic valvar regurgitation are not defined. I hypothesized
      that, in children with chronic mitral or aortic regurgitation, an index for
      decompensation could be created by using the ratio of the diastolic left
      ventricular wall thickness to the radius, and that such an index could prove
      useful in determining the optimal time for surgical intervention. METHODS: The
      left ventricular echocardiograms were obtained at the tips of the leaflets of the
      mitral valve by M-mode echocardiography. The diastolic septal wall thickness was
      measured between the right and left ventricular endocardial layers, and the
      posterior wall thickness between the endocardium and the interphase between the
      epicardium and the myocardium. The left ventricular diastolic dimension was then
      measured, between the posterior and septal wall endocardial layers, and systolic
      dimension as the smallest distance detected between these layers. All diastolic
      measurements were made at the time of the R wave of electrocardiogram, using the
      leading edge technique. The ratio of wall thickness was measured using the mean
      of septal and posterior wall thicknesses divided by half the diastolic
      dimensions, the normalized thickness of the wall previously referred to as the
      h/r ratio and relative mural thickness. RESULTS: The ratio of wall thickness to
      left ventricular radius, and its relation to systolic left ventricular pressure
      or systolic blood pressure, was found to be linear in 89 normal school children,
      and 39 children with aortic stenosis. For future predictions, I calculated the
      95th percentile limits and the 95th percentile confidence bands for this
      relation. Using the same data, it proved possible to calculate ratios of wall
      thickness for various ranges of either systolic blood pressure or left
      ventricular peak pressure. By using the normal limits of 0.356 plus or minus
      0.0316 of the ratio, appropriate for the systolic blood pressure of children with
      mitral regurgitation, I determined the adequacy of the ratio of wall thickness.
      Of the children, 51 were in ventricular failure, and these had an inadequate
      ratio, below two standard deviation. Of the others, 21 had an inadequate ratio to
      within minus one to minus two standard deviations, and 12 of these were
      asymptomatic, 8 were symptomatic, but only one was in ventricular failure. For 18
      children with aortic regurgitation, using the same limits, one child was within 1
      standard deviation and was asymptomatic, 8 fell within minus 1 to minus 2
      standard deviations and 2 of these were symptomatic, 5 were in ventricular
      failure, and 1 was asymptomatic, while the other 9 had ratios falling less than
      minus 2 standard deviations, and all were in ventricular failure. CONCLUSION: I
      conclude that the index of normalized wall thickness defined as the ratio of the
      left ventricular wall thickness to its radius is adequate, and within normal
      limits, when there is compensated volume overload, but is inadequate and below
      normal limits when the volume overloaded left ventricle becomes decompensated. My
      data suggests that the persistently decreasing ratio of wall thickness below the
      limits of normality serves as an indicator of ventricular decompensation, and
      thus can be used as a new criterion for determining the optimal time for surgical
      intervention.

PMID- 16297253
TI  - Recent results of pulmonary arterial angioplasty: the differences between
      proximal and distal lesions.
AB  - INTRODUCTION: We sought to establish a modern understanding of the safety and
      efficacy of trans-catheter pulmonary arterial angioplasty. METHODS: A review of
      records in a sample of 104 dilations, out of a total of 711 procedures undertaken
      between January, 1996 and December, 2000, provided descriptive information
      regarding technique, adverse events, and changes achieved in luminal diameter.
      Because evidence during the review of angiograms suggested substantial
      differences according to whether the stenotic lesions were positioned proximally
      or distally within the pulmonary arterial tree, all analyses incorporated this
      classification. RESULTS: We reviewed stenoses in 203 pulmonary arteries, 38%
      located proximally and 62% distally, with follow-up available concerning dilation
      in 92 vessels. Proximal dilations frequently involved a prior surgical site, and
      appeared more compliant and amenable to conventional angioplasty, as evidenced by
      more common elimination of the waist, but also more recoil, then requiring
      placement of stents. In contrast, distal lesions frequently required balloons
      capable of sustaining high pressures of inflation, and larger balloons relative
      to the size of the vessels. The proportional increase in diameter was greater for
      distal sites, at 90 plus or minus 77%, compared to proximal, at 64 plus or minus
      70%, p equal to 0.002. Serious adverse events occurred in 3 of 104 procedures,
      giving a rate of serious adverse events of 2.9%. At follow-up, 9 of 92 vessels
      (10%), 95% confidence intervals from 5% to 18%, returned to their diameters prior
      to dilation, with no difference in the rate of restenosis according to the site
      of dilation. CONCLUSION: Our findings indicate the need to distinguish, and to
      consider, the important differences in technical issues and outcomes, when
      performing dilations at proximal as opposed to distal sites. Although angioplasty
      is effective therapy for pulmonary arterial stenosis, a subset of vessels, more
      often distal, remain resistant to conventional techniques.

PMID- 16297255
TI  - The electrophysiology of atrioventricular nodal reentry tachycardia following the
      Mustard or Senning procedure and its radiofrequency ablation.
AB  - We describe the electrophysiological studies undertaken in four patients with
      atrioventricular nodal reentry tachycardia in the setting of concordant
      atrioventricular and discordant ventriculo-arterial connections (transposition).
      Radiofrequency ablation was attempted in three, all with success. Clear evidence
      of dual antegrade pathways through the atrioventricular node was present in only
      one of the four, but other characteristics of discrete fast and slow pathways
      into the atrioventricular node were present in all. Atrioventricular nodal
      reentry tachycardia was inducible in all. In the three patients in whom ablation
      was attempted, the application of radiofrequency energy to the low medial regions
      of the systemic venous atrium (morphologically left) consistently caused
      junctional accelerated rhythm, but these lesions were not successful in
      eliminating the tachycardia. Successful radiofrequency ablation required a
      retrograde approach to the region of the slow pathway in the pulmonary venous
      atrium (morphologically right).

PMID- 16297254
TI  - Follow-up results of Cutting Balloon angioplasty used to relieve stenoses in
      small pulmonary arteries.
AB  - BACKGROUND: We sought to determine if the acute gains in pulmonary arterial
      diameter achieved by using Cutting Balloons to dilate stenoses in small arteries
      are maintained at follow-up. METHODS: A search of our database identified all
      patients who underwent dilation with Cutting Balloons for pulmonary arterial
      stenosis between June 2001 and September 2003. We reviewed the procedural and
      angiographic data obtained at the initial and follow-up procedures. RESULTS: Over
      the period of study, 29 patients with a median age of 3.7 years, and a range from
      0.4 to 46.6, underwent treatment with Cutting Balloons at 41 procedures for one
      or more pulmonary arterial obstructions resistant to conventional angioplasty. At
      the initial procedure, we enlarged 79 vessels, with an initial minimal luminal
      diameter of 1.5 plus or minus 0.8 millimetres, to a diameter of 3.0 plus or minus
      1.1 millimetres (p smaller than 0.001). Angiographic data indicated that 49% of
      the vessels showed evidence of vascular damage not requiring intervention, while
      stents were placed in 9 vessels. Follow-up angiography was available for 39 of
      the vessels, evaluated at a median of 6 months, with a range from 3 to 24 months,
      after the initial procedure. In these vessels, there was a mean loss of 10 plus
      or minus 25% in luminal diameter, p not significant. Of the 39 vessels, 8 had
      returned to a diameter within half of the initial diameter, giving a failure rate
      at follow-up of 21%, with 95% confidence intervals from 9% to 36%. All
      complications were identified within 24 hours of the catheterization procedure,
      and there were no late complications or deaths during the period of follow-up.
      Placement of stents produced both greater increases in diameter at the initial
      procedure (p smaller than 0.001), and greater losses at follow-up (p equal to
      0.01). CONCLUSIONS: Despite the frequent identification of intravascular trauma,
      initial gains in luminal diameter after use of Cutting Balloons to dilate
      stenotic pulmonary arteries are maintained at follow-up.

PMID- 16297257
TI  - Results of surgical treatment for infective endocarditis in children.
AB  - OBJECTIVE: Infective endocarditis is uncommon condition, with a high degree of
      morbidity and mortality. It is less common in children, albeit tending to be
      associated with congenital cardiac malformations. We describe our experience of
      the need for surgical treatment in children with infective endocarditis. PATIENTS
      AND METHODS: We analyzed retrospectively the records of 9 children aged below 16
      years seen between May 2003 and March 2005 with infective endocarditis, reviewing
      the demographic details, clinical presentation, microbiological and
      echocardiographic data, operative findings, and outcome. RESULTS: Apart from pre
      existing renal insufficiency in 1 patient, congenital cardiac malformations were
      the predisposing factors. Blood cultures were positive in 3, but remained
      negative in the other 6 patients. The indications for surgical treatment included
      uncontrolled sepsis, congestive heart failure, recurrent endocarditis, patch or
      graft dehiscence, and pseudoaneursymal formation. Death due to uncontrolled
      sepsis resulting in multiorgan failure occurred in 1 patient, who had tetralogy
      of Fallot with pulmonary atresia and major aortopulmonary collateral arteries.
      Another patient died late postoperatively due to cardiac failure after relapse of
      the endocarditis in the setting of negative blood cultures. CONCLUSION: Despite
      advances in antimicrobial therapy, diagnosis, and measures of treatment for
      infective endocarditis, complications continue to be responsible for substantial
      morbidity and mortality. Since blood cultures are frequently negative, clinical
      and echocardiographic findings should be the major determinants of strategies
      used for treatment. We believe that our small series of patients seen over the
      past two years in which surgical treatment was performed will be helpful in
      guiding the clinical perspectives for children with infective endocarditis.

PMID- 16297256
TI  - Subtle infective endocarditis and congenital cardiac disease.
AB  - Congenital cardiac disease is recognized as a major predisposing substrate for
      infective endocarditis. We present three cases of unanticipated intraoperative
      discovery of vegetations in patients with congenital cardiac malformations
      without preoperative clinical, laboratory or echocardiographic evidence of
      infective endocarditis, and their successful treatment. The relevant literature
      is reviewed, with emphasis of the need to maintain a high index of suspicion for
      the presence of endocarditis during repair of congenital cardiac lesions.

PMID- 16297258
TI  - Impact of arrhythmias on health-related quality of life in adults with congenital
      cardiac disease.
AB  - BACKGROUND: Health-related quality of life in adults with congenital cardiac
      disease appears to be impaired, but the determinants of this alteration remain
      largely unknown. The aim of our study was to examine the impact of arrhythmias on
      quality of life in patients late after the atrial redirection operation for
      transposition, or after complete correction of tetralogy of Fallot. PATIENTS AND
      METHODS: We enrolled 32 patients with transposition, and 35 patients with
      tetralogy of Fallot, in a prospective study. Quality of life was assessed using
      RAND-36 questionnaires. Quality of life data were compared with those of an age
      matched control population. Patients underwent 24-hour and 7-day
      electrocardiographic recordings, echocardiography, and exercise testing. RESULTS:
      Patients without arrhythmias had quality of life comparable to that of the
      general population. All 8 domains in the questionnaire showed scores 22 to 51
      percent lower in 12 patients with atrial tachyarrhythmias, and/or sinus nodal
      dysfunction, requiring insertion of a pacemaker in comparison with 55 patients
      without arrhythmias. In patients with transposition, low scores were not only
      associated with arrhythmias, but also correlated with impaired exercise capacity.
      CONCLUSIONS: Atrial tachyarrhythmias, and sinus nodal dysfunction, requiring
      insertion of a pacemaker, were associated with impaired quality of life in adults
      late after atrial surgical correction of transposition or correction of tetralogy
      of Fallot.

PMID- 16297259
TI  - Echocardiographic and electrocardiographic identification of those children with
      hypertrophic cardiomyopathy who should be considered at high-risk of dying
      suddenly.
AB  - BACKGROUND: Hypertrophic cardiomyopathy is a common cause of sudden death in
      children. In this study, we aimed to identify clinical measures for
      stratification of this risk in childhood. PATIENTS AND METHODS: By means of a
      retrospective cohort study from six regional centres of paediatric cardiology, we
      identified 128 patients with hypertrophic cardiomyopathy presenting below 19
      years of age, with a mean follow-up of 10.8 years. Of the patients, 31 had died,
      16 suddenly, with a median age at sudden death of 13.3 years. RESULTS: Cox
      regression shows that electrocardiographic voltages, analysed as the sum of the R
      and S waves in all six limb leads (p equal to 0.001), and septal thickness
      expressed as proportion of the 95th centile for age (p equal to 0.036), were
      independent predictors of sudden death. When the sum of the R and S waves is over
      10 millivolts, the odds ratio for sudden death was 8.4, with 95% confidence
      intervals from 2.2 to 33.7 (p equal to 0.0012), and finding a septal thickness
      over 190% of 95th centile for age gives an odds ratio of 6.2, with confidence
      intervals from 1.5 to 25.1 (p equal to 0.011). Noonan's syndrome, with a p value
      equal to 0.043, and the ratio of the left ventricular wall to its cavity in
      diastole, with a p value equal to 0.005, were independent predictors of death in
      cardiac failure, with a ratio of the mural thickness to the dimension of the
      cavity over 0.30 giving an odds ratio of 36.0, with confidence limits from 4.2 to
      311, and a p value equal to 0.00009. At follow-up, patients deemed to be at a
      high risk of dying suddenly were identified by the combination of the sum of the
      R and S waves greater than 10 millivolts and septal thickness over 190%, with a
      sensitivity of 91%, specificity of 78%, positive predictive value of 50%, and a
      negative predictive value of 97%. CONCLUSIONS: Children at high risk of dying
      suddenly with hypertrophic cardiomyopathy, with a subsequent annual mortality of
      6.6%, can be distinguished at the time of diagnosis from those patients having a
      low risk of sudden death, the latter with an annual mortality of 0.27%.

PMID- 16297261
TI  - Left and right ventriculo-arterial coupling in a patient with congenitally
      corrected transposition.
AB  - The single beat method was used to evaluate right and left ventriculo-arterial
      coupling in an asymptomatic patient with congenitally corrected transposition.
      The ratio of ventricular end-systolic to arterial elastances was normal for the
      left ventricle coupled to the pulmonary circulation, and depressed for the right
      ventricle coupled to the systemic circulation. This result suggests that chronic
      uncoupling of the right ventricle to the systemic circulation might play a role
      in the pathophysiology produced by congenitally corrected transposition.

PMID- 16297260
TI  - A rare association of major aorto-pulmonary collaterals with right isomerism and
      totally anomalous pulmonary venous drainage.
AB  - A female neonate, born at term, presented with complex cardiac anatomy dominated
      by right isomerism and infra-diaphragmatic totally anomalous pulmonary venous
      connection. Surgical repair was performed using circulatory arrest under deep
      hypothermia. In the postoperative period, the patient could not be weaned off
      mechanical ventilation, and underwent cardiac catheterization. This revealed
      major aortopulmonary collateral arteries, which were occluded with coils. We
      review the literature with specific focus on the occurrence of this unusual
      combination and its implication in the management during the postoperative
      period.

PMID- 16297262
TI  - Hypoplasia of the left heart with discordant ventriculoarterial connections.
AB  - We report the rare combination of a severely hypoplastic left ventricle and
      discordant ventriculoarterial connections, with associated subpulmonary
      obstruction of the left ventricular outflow tract. The long tortuous arterial
      duct originated at an acute angle from the aorta, suggesting that the
      subpulmonary obstruction developed early in fetal life. Residual flow via the
      hypoplastic left ventricle to the pulmonary circulation after insertion of an
      aortopulmonary shunt resulted in haemodynamic deterioration, which was instantly
      reversed by closing the pulmonary trunk.

PMID- 16297263
TI  - Ventricular fibrillation following removal of temporary epicardial pacemaking
      wires.
AB  - Temporary wires are routinely sutured to both the atrial and ventricular
      epimyocardium after open heart surgery. Despite their rarity, complications
      related to removal of such pacemaking wires may cause life threatening
      situations. We describe here a patient who developed ventricular fibrillation
      immediately after removal of temporary epicardial pacemaking wires.

PMID- 16297264
TI  - Prenatal diagnosis of tetralogy of Fallot with obstructed supracardiac totally
      anomalous pulmonary venous connection.
AB  - We describe our experience with prenatal diagnosis of tetralogy of Fallot with
      supracardiac totally anomalous pulmonary venous connection. We also suspected
      obstruction in the ascending vertical vein as it crossed the right bronchus and
      coursed superiorly to join the right superior caval vein. This finding was
      confirmed on postnatal echocardiography, and at autopsy.

PMID- 16297265
TI  - Extracorporeal membrane oxygenation as a bridge to surgical treatment of flail
      tricuspid valve in a neonate.
AB  - A term infant rapidly developed profound cyanosis and metabolic acidosis shortly
      after an uncomplicated vaginal delivery. Echocardiography identified a flail
      antero-superior leaflet of the tricuspid valve, which was producing severe
      tricuspid insufficiency. The clinical state deteriorated despite maximal medical
      management, and the patient was placed on venoarterial extracorporeal membrane
      oxygenation. Within twenty-four hours, the metabolic acidosis corrected,
      inotropic support was discontinued, and the patient was weaned to minimal
      ventilator settings. Successful repair of the tricuspid valve was performed two
      days later.

PMID- 16297266
TI  - Subneoaortic stenosis complicating the arterial switch operation.
AB  - We report obstruction of the reconstructed left ventricular outflow tract
      diagnosed 18 months after an arterial switch operation that included closure of a
      ventricular septal defect. We speculate that either turbulences created by the
      patch used to close the ventricular septal defect, or postoperative modifications
      of ventricular geometry, were responsible for producing this unusual
      complication.

PMID- 16297267
TI  - Anatomical imaging of severe coarctation in childhood.

PMID- 16297268
TI  - Aortic coarctation in an infant with tetralogy and pulmonary atresia.

PMID- 16297272
TI  - Proposals for general requirements for training institutes in paediatric
      cardiology.

PMID- 16297270
TI  - Lionel Malcolm Bargeron, Jr (1923-2005): Ars longa, vita brevis.

PMID- 16297273
TI  - Recommendations for training in paediatric cardiology.

PMID- 16297278
TI  - On the choice of the offspring population size in evolutionary algorithms.
AB  - Evolutionary algorithms (EAs) generally come with a large number of parameters
      that have to be set before the algorithm can be used. Finding appropriate
      settings is a difficult task. The influence of these parameters on the efficiency
      of the search performed by an evolutionary algorithm can be very high. But there
      is still a lack of theoretically justified guidelines to help the practitioner
      find good values for these parameters. One such parameter is the offspring
      population size. Using a simplified but still realistic evolutionary algorithm, a
      thorough analysis of the effects of the offspring population size is presented.
      The result is a much better understanding of the role of offspring population
      size in an EA and suggests a simple way to dynamically adapt this parameter when
      necessary.

PMID- 16297279
TI  - Empirical analysis of locality, heritability and heuristic bias in evolutionary
      algorithms: a case study for the multidimensional knapsack problem.
AB  - Our main aim is to provide guidelines and practical help for the design of
      appropriate representations and operators for evolutionary algorithms (EAs). For
      this purpose, we propose techniques to obtain a better understanding of various
      effects in the interplay of the representation and the operators. We study six
      different representations and associated variation operators in the context of a
      steady-state evolutionary algorithm for the multidimensional knapsack problem.
      Four of them are indirect decoder-based techniques, and two are direct encodings
      combined with different initialization, repair, and local improvement strategies.
      The complex decoders and the local improvement and repair strategies make it
      practically impossible to completely analyze such EAs in a fully theoretical way.
      After comparing the general performance of the chosen EA variants for the
      multidimensional knapsack problem on two benchmark suites, we present a hands-on
      approach for empirically analyzing important aspects of initialization, mutation,
      and crossover in an isolated fashion. Static, inexpensive measurements based on
      randomly created solutions are performed in order to quantify and visualize
      specific properties with respect to heuristic bias, locality, and heritability.
      These tests shed light onto the complex behavior of such EAs and point out
      reasons for good or bad performance. In addition, the proposed measures are also
      examined during actual EA runs, which gives further insight into dynamic aspects
      of evolutionary search and verifies the validity of the isolated static
      measurements. All measurements are described in a general way, allowing for an
      easy adaption to other representations and problems.

PMID- 16297280
TI  - RGFGA: an efficient representation and crossover for grouping genetic algorithms.
AB  - There is substantial research into genetic algorithms that are used to group
      large numbers of objects into mutually exclusive subsets based upon some fitness
      function. However, nearly all methods involve degeneracy to some degree. We
      introduce a new representation for grouping genetic algorithms, the restricted
      growth function genetic algorithm, that effectively removes all degeneracy,
      resulting in a more efficient search. A new crossover operator is also described
      that exploits a measure of similarity between chromosomes in a population. Using
      several synthetic datasets, we compare the performance of our representation and
      crossover with another well known state-of-the-art GA method, a strawman
      optimisation method and a well-established statistical clustering algorithm, with
      encouraging results.

PMID- 16297281
TI  - Evaluating the epsilon-domination based multi-objective evolutionary algorithm
      for a quick computation of Pareto-optimal solutions.
AB  - Since the suggestion of a computing procedure of multiple Pareto-optimal
      solutions in multi-objective optimization problems in the early Nineties,
      researchers have been on the look out for a procedure which is computationally
      fast and simultaneously capable of finding a well-converged and well-distributed
      set of solutions. Most multi-objective evolutionary algorithms (MOEAs) developed
      in the past decade are either good for achieving a well-distributed solutions at
      the expense of a large computational effort or computationally fast at the
      expense of achieving a not-so-good distribution of solutions. For example,
      although the Strength Pareto Evolutionary Algorithm or SPEA (Zitzler and Thiele,
      1999) produces a much better distribution compared to the elitist non-dominated
      sorting GA or NSGA-II (Deb et al., 2002a), the computational time needed to run
      SPEA is much greater. In this paper, we evaluate a recently-proposed steady-state
      MOEA (Deb et al., 2003) which was developed based on the epsilon-dominance
      concept introduced earlier(Laumanns et al., 2002) and using efficient parent and
      archive update strategies for achieving a well-distributed and well-converged set
      of solutions quickly. Based on an extensive comparative study with four other
      state-of-the-art MOEAs on a number of two, three, and four objective test
      problems, it is observed that the steady-state MOEA is a good compromise in terms
      of convergence near to the Pareto-optimal front, diversity of solutions, and
      computational time. Moreover, the epsilon-MOEA is a step closer towards making
      MOEAs pragmatic, particularly allowing a decision-maker to control the achievable
      accuracy in the obtained Pareto-optimal solutions.

PMID- 16297282
TI  - Active vision and receptive field development in evolutionary robots.
AB  - In this paper, we describe the artificial evolution of adaptive neural
      controllers for an outdoor mobile robot equipped with a mobile camera. The robot
      can dynamically select the gazing direction by moving the body and/or the camera.
      The neural control system, which maps visual information to motor commands, is
      evolved online by means of a genetic algorithm, but the synaptic connections
      (receptive fields) from visual photoreceptors to internal neurons can also be
      modified by Hebbian plasticity while the robot moves in the environment. We show
      that robots evolved in physics-based simulations with Hebbian visual plasticity
      display more robust adaptive behavior when transferred to real outdoor
      environments as compared to robots evolved without visual plasticity. We also
      show that the formation of visual receptive fields is significantly and
      consistently affected by active vision as compared to the formation of receptive
      fields with grid sample images in the environment of the robot. Finally, we show
      that the interplay between active vision and receptive field formation amounts to
      the selection and exploitation of a small and constant subset of visual features
      available to the robot.

PMID- 16297284
TI  - Diagnostic Performance of Triagetrade mark for Benzodiazepines: Urine Analysis of
      the Dose of Therapeutic Cases.
AB  - We evaluated the diagnostic performance of Triage for benzodiazepines in 74 urine
      specimens from outpatients given therapeutic doses of benzodiazepines and
      compared the results of EMIT assays. Results obtained in all urine samples were
      confirmed using liquid chromatography-mass spectrometry (LC-MS). Overall
      agreement between results of Triage and EMIT assays was 73%. All of the Triage
      positive samples were also positive by EMIT assays. Results of Triage and EMIT
      assays were different for 20 samples obtained from patients given
      thienodiazepines (etizolam, brotizolam, and clotiazepam) and nitrobenzodiazepines
      (nitrazepam, flunitrazepam, and clonazepam). LC-MS confirmed parent drugs in
      urine specimens, consistent with the prescriptions of drugs. The low agreement
      between Triage and EMIT results in this study might be due to low sensitivity of
      Triage for thienodiazepines. Thienodiazines are frequently prescribed
      benzodiazepines, and Triage panel is the most frequently used screening kit in
      Japan. It should be noted that negative results obtained by a Triage test might
      not mean the absence of thienodiazepines.

PMID- 16297285
TI  - Chloroquine-treatment failure in northern Ghana: roles of pfcrt T76 and pfmdr1
      Y86.
AB  - Although chloroquine (CQ) monotherapy is now generally inadequate for the
      treatment of Plasmodium falciparum malaria in northern Ghana--recently, 58% of
      225 children failed treatment by day 14--use of the drug continues because of its
      low cost and wide availability. The risk factors associated with CQ-treatment
      failure in this region of Africa, including the T76 mutation in the chloroquine
      resistance transporter (pfcrt) gene and the Y86 mutation in the multidrug
      resistance (pfmdr1) gene of P. falciparum, have now been investigated, and
      genotype-failure indices (GFI) have been calculated. Treatment failure was found
      to be associated with young age, poor nutritional status, pfcrt T76 and pfmdr1
      Y86, and early treatment failure (ETF) was also associated with high
      parasitaemia. The presence and concentration of 'residual' CQ in the blood of
      patients immediately before they were treated with CQ for the present study
      appeared to have no effect on outcome. Presence at recruitment of pfcrt T76 or
      pfmdr1 Y86 or both mutations increased the risk of treatment failure by 3.2-, 2.4
      and 4.5-fold, and the risk of ETF by 9.8-, 2.7- and 10.2-fold, respectively. The
      pfcrt T76 GFI for clinical and all treatment failures were 2.8 and 1.4,
      respectively. These indices were relatively low in the younger children, those
      with malnutrition, and those with high parasitaemias when treated. Residual CQ
      did not affect the GFI substantially. Both pfcrt T76 and, to a lesser extent,
      pfmdr1 Y86 would be useful tools for the surveillance of CQ resistance in
      northern Ghana. In the current transition phase to alternative first-line
      treatment for P. falciparum malaria, it should be possible to provide estimates
      of the level of CQ resistance by monitoring the prevalences of these mutations.

PMID- 16297286
TI  - Itraconazole or allopurinol in the treatment of chronic American trypanosomiasis:
      the results of clinical and parasitological examinations 11 years post-treatment.
AB  - Eleven years after they had been given itraconazole or allopurinol for the
      treatment of chronic American trypanosomiasis, 109 adult patients were checked
      for electrocardiographic abnormalities and evidence of Trypanosoma cruzi
      infection. The parasitological investigations included xenodiagnosis, in which
      the faeces of Triatoma infestans that had fed on the patients were checked under
      the microscope for flagellates. In addition, a PCR-based assay and a
      hybridization assay were used to test blood samples from the patients, and faeces
      from the Tri. infestans that had fed on the patients, for Try. cruzi DNA. For the
      data analysis, the patients were divided into four groups known as normal/normal,
      abnormal/normal, normal/abnormal and abnormal/abnormal, according to whether the
      patients had been found to have normal or abnormal electrocardiograms (ECG)
      shortly before the first treatment and to have normal or abnormal ECG when
      checked at the 11-year follow-up. The 51 normal/normal and 24 normal/abnormal
      patients were assumed to have been in the 'indeterminate' phase of the disease
      when they were treated, whereas the 16 abnormal/normal and 18 abnormal/abnormal
      patients all had evidence of chagasic cardiopathy at that time. When checked 11
      years post-treatment, 40 (78.4%), 17 (70.8%), 14 (87.5%) and 17 (94.4%) of these
      patients, respectively, were each found positive for Try. cruzi in at least one
      of the parasitological tests. The hybridization assay, whether applied to human
      blood or bug faeces, appeared a significantly more sensitive test than the PCR
      based assays or microscopically assessed xenodiagnosis (P<0.05). Only the 21
      patients who appeared to be negative for Try. cruzi could be considered
      parasitologically cured (although all still appeared to have anti-Try. cruzi
      antibodies in their blood). Only 13 of these parasitologically cured patients
      (seven of those treated with itraconazole and six of those given allopurinol) had
      normal ECG at the 11-year follow-up. In Chile at least, itraconazole, which
      caused fewer adverse effects than the allopurinol while being no less effective
      at preventing cardiopathy, appears to be the drug of choice to treat chronic
      American trypanosomiasis in adults.

PMID- 16297287
TI  - Usefulness of the direct agglutination test in the early detection of subclinical
      Leishmania donovani infection: a community-based study.
AB  - The value of a direct agglutination test (DAT) in the detection of subclinical
      infections with Leishmania donovani has recently been investigated in the Indian
      state of Bihar, after the sensitivity and specificity of the test had been
      determined. When used to screen sera from 108 parasitologically confirmed cases
      of visceral leishmaniasis, 50 patients with active, non-leishmanial infection,
      and 641 healthy controls living close to, or distant from, an endemic area, the
      test was found to be 91.7% sensitive and 100% specific if a titre of 1:800 was
      used as the threshold for seropositivity. During a longitudinal clinical study in
      a rural, VL-endemic area of the Indian state of Bihar, the test was used, with
      1:800 set as the threshold titre, to determine the baseline prevalence of
      infection with L. donovani among villagers who, though showing no symptoms of VL,
      had recently been febrile for at least 2 weeks. The 234 subjects of this study
      were either VL-case contacts [i.e. members of households in which there were
      active or cured VL cases (N=78)] or the members of control households with no
      cases or history of the disease (N=156). The results of DAT at the start of the
      study indicated that 49 (20.9%) of the subjects--29 (37.2%) of the VL-case
      contacts and 20 (12.8%) of the other subjects--were seropositive and therefore
      probably had subclinical infections with L. donovani. During the subsequent 9
      months of follow-up, however, only eight of the subjects found seropositive at
      the start of the study--seven (24.1%) of the seropositive case contacts but only
      one (5.0%) of the other seropositives--developed symptomatic VL, all by month 6
      of the follow-up. Compared with their neighbours, therefore, individuals who
      shared households with active or cured cases of VL appeared at greater risk not
      only of L. donovani infection (indicating focal transmission) but also of
      developing symptomatic disease once infected. Curiously, among the seropositive
      case contacts, those from the households that harboured active cases of VL at the
      baseline survey were less likely to develop symptomatic VL during the 9 months of
      follow-up than those from households that harboured only cured cases (18.8% v.
      30.8%). The wide-spread use of DAT could allow the detection and early treatment
      of latent L. donovani infections and so contribute to the elimination of VL, at
      least as a public-health problem, from India.

PMID- 16297288
TI  - Pathogenic Acanthamoeba strains from water sources in Jamaica, West Indies.
AB  - In 2004, samples of tap water and of river and sea water associated with human
      activities were collected in Jamaica, West Indies, and checked for free-living
      Acanthamoeba. The morphologies of the cysts and trophozoites observed and the
      results of PCR-based amplifications with a genus-specific primer pair were used
      to identify the Acanthamoeba isolates. The potential of each isolate as a human
      pathogen was then evaluated using thermotolerance and osmotolerance assays and
      two PCR-based assays for Acanthamoeba pathogenesis. Acanthamoeba were identified
      in 36.1%, 26.4% and 49.6% of the tap-, river- and sea-water samples collected,
      respectively. Pathogenic potential was shown by 60.0% of the Acanthamoeba strains
      isolated from tap water, 68.4% of the strains from river water, and 40.4% of the
      seawater strains. Sequencing of ribosomal DNA revealed the T1, T2, T4, T5, T7, T9
      and T11 genotypes. Isolates of the T4 genotype were collected from tap, rain and
      sea water and, as expected, exhibited the most pathogenic traits; most were
      osmotolerant, thermotolerant and expressing extracellular serine protease. This
      is the first study of the occurrence and distribution of Acanthamoeba in water in
      the West Indies, and the results confirm the presence of potentially pathogenic
      strains in Jamaica.

PMID- 16297289
TI  - Bancroftian filariasis in children and adolescents: clinical-pathological
      observations in 22 cases from an endemic area.
AB  - In areas where bancroftian filariasis is endemic, the clinical manifestations of
      the disease, which are often very varied, appear most frequently during early
      adulthood or later. In consequence, very little attention, if any, has been given
      to the signs and symptoms of the disease in childhood. In an attempt to fill this
      gap, clinical and pathological observations were made, in Brazil, on 22 children
      (aged 2-15 years) who were infected with Wuchereria bancrofti. There was a
      predominance of lymph-node involvement. In all but three (14%) of the children
      (who had adult parasites in their intrascrotal lymphatic vessels), the adult
      worms were located in the afferent or efferent vessels of draining lymph nodes,
      predominantly in the inguinal region. None of the patients presented with distal
      lymphoedema, and the adenopathy was characterized by painless, localized, lymph
      node enlargement, without signs of inflammation in the overlying skin.
      Histologically, the alterations in the lymphatic vessels and surrounding
      structures were similar to those described in adult patients, and depended
      essentially on adult-parasite viability. The localization of the adult worms in
      the paediatric cases was peculiar and distinct from that observed in adult
      patients, in whom the adult parasites are usually found in extra-nodal lymphatic
      vessels. In areas endemic for bancroftian filariasis, therefore, filarial
      infection should be considered as a possible cause of adenopathy. For the
      differential diagnosis of adenopathy in young patients from endemic areas, the
      authors recommend the use of ultrasound and other non-invasive diagnostic tools,
      as alternatives to excisional biopsies, which are often unnecessary in
      bancroftian filariasis.

PMID- 16297291
TI  - Delays to treatment and out-of-pocket medical expenditure for tuberculosis
      patients, in an urban area of South America.
AB  - Short delays to treatment are important for the control of tuberculosis (TB).
      National Tuberculosis Programmes provide free diagnosis and treatment for smear
      positive patients, so that the patients' out-of-pocket medical expenditure could
      be almost nil. The factors associated with delays in starting treatment, and the
      pre-treatment out-of-pocket medical expenditure for TB patients, have now been
      investigated in the Bolivian city of Cochabamba. Bolivia is the Latin American
      country with the highest incidence of TB. It is covered by a national TB
      programme that provides free diagnosis and free treatment for smear-positive
      patients. Structured interviews with 144 smear-positive patients enrolled in this
      programme revealed median patient, provider and total delays of 3.6, 6.2 and 12.9
      weeks, respectively. The total delays were longer for the female patients than
      for the male, and for patients who consulted private doctors than for the other
      patients. When the first healthcare provider was a doctor, the median provider
      delay was 4.9 weeks in the public sector but 7.2 weeks in the private. The median
      out-of-pocket medical expenditure per patient, which was U.S.$13.2 overall, was
      much higher for those who consulted a private doctor than for those who did not
      (U.S.$21.9 v. U.S.$5.4, respectively; P<0.001). It appears that interventions
      targeting doctors (in both the private and public sectors) are likely to have a
      larger impact on the shortening of delays in TB treatment than interventions
      targeting patients. They could also reduce unnecessary out-of-pocket expenditure.

PMID- 16297293
TI  - Carriage by the housefly (Musca domestica) of multiple-antibiotic-resistant
      bacteria that are potentially pathogenic to humans, in hospital and other urban
      environments in Misurata, Libya.
AB  - Using standard microbiological procedures, bacteria that are potentially
      pathogenic to humans were isolated from 150 houseflies collected in the Libyan
      city of Misurata (50 flies each from the Central Hospital, streets and abattoir).
      Salmonella spp., Yersinia enterocolitica and Edwardsiella tarda were isolated
      from flies collected on the streets and in the abattoir but not from those
      collected in the hospital. Shigella sonnei was detected in just one fly, which
      was collected in the abattoir. Of the flies collected in the hospital, streets
      and abattor, 42%, 42% and 32% were positive for Escherichia coli, 70%, 50% and
      62% for Klebsiella spp., 2%, 20% and 10% for Aeromonas spp., 96%, 36% and 34% for
      Pseudomonas spp., 20%, 12% and 16% for Staphylococcus spp., and 24%, 22% and 18%
      for Streptococcus spp., respectively. When the antibiotic susceptibilities of the
      fly isolates were investigated, the Enterobacteria isolated from the houseflies
      collected in the hospital were found to be resistant to significantly more of the
      commonly used antibiotics that were tested than the Enterobacteria isolated from
      the flies caught in the streets or abattoir. Whatever the source of the flies
      from which they were collected, the Pseudomonas isolates frequently showed
      resistance to multiple antibiotics, with >50% each being resistant to at least 10
      antimicrobial agents. Two isolates of Sta. aureus (both from flies collected in
      the hospital) were resistant to methicillin. The present study supports the
      belief that the housefly is a potential vector of multiple-antibiotic-resistant,
      pathogenic bacteria, including methicillin-resistant Sta. aureus, in the hospital
      environment. Given their mobility, it seems likely that houseflies carry such
      pathogens from hospitals to surrounding communities, and vice versa.

PMID- 16297292
TI  - A 12-case outbreak of pharyngeal plague following the consumption of camel meat,
      in north-eastern Jordan.
AB  - Between late January and early February 1997, an outbreak of plague, associated
      with cervical lymphadenopathy and fever, occurred in the Jordanian village of
      Azraq ad-Druze, which lies about 50 km west of the border with Saudi Arabia. The
      12 cases who presented at hospital were initially assumed to have tularaemia, and
      all were successfully treated with gentamicin. When, however, their sera were
      tested for evidence of Yersinia pestis or Francisella tularensis infection (using
      haemagglutination, enzyme immuno-assays for specific IgM or the F1 antigen of Y.
      pestis, and micro-agglutination tests), all 12 were found to have anti-Y. pestis
      IgM. Three dogs shot near the Saudi Arabian border were also found seropositive
      for antibodies against Y. pestis. Eleven of the 12 patients reported that, 2-4
      days before their symptoms appeared, they had eaten the meat cut from the carcass
      of the same camel, either raw (10 cases) or cooked (one case). All 12 patients
      were diagnosed as cases of pharyngeal plague (the first cases of plague reported
      in Jordan for more than 80 years), caused by Y. pestis that most had acquired
      when they ate raw meat from a camel that was infected with the pathogen.

PMID- 16297290
TI  - The rapid monitoring of ivermectin treatment: will school-based surveys provide
      the answer?
AB  - The data on ivermectin-treatment coverage recorded in household surveys sometimes
      conflict with those recorded in school-based surveys or in the relevant treatment
      registers maintained by community-directed distributors (CDD). An attempt has now
      been made, in two sites in Nigeria (Enugu and Kaduna states) and one in Sudan
      (Abu Hamad province), to determine how well these three sets of data are
      correlated (and to explore the effectiveness of several alternative channels for
      the delivery of treatment-monitoring forms to schools). Using a cross-sectional
      approach, data were collected from primary schools, households and treatment
      registers. Calculation of Pearson's correlation coefficients (r) indicated that,
      overall, the data from the household surveys were very similar to those collected
      using the school-based strategy (r=0.66; P<0.0001) or from the treatment
      registers of the CDD (r=0.86; P<0.0001). The information recorded in the CDD
      registers also closely matched that recorded in the school-based surveys (r=0.67;
      P<0.0001). These encouraging results for the pooled data masked some inter-site
      differences. The correlation between the household-survey and treatment-register
      data was, for example, only good in Enugu (r=0.89; P<0.001), and was too weak to
      be statistically significant in Abu Hamad or Kaduna. Although the results of the
      school-based survey in Kaduna also did not closely correlate with those of the
      corresponding household survey (r=0.10; P=0.71), the household survey at this
      site was probably not conducted as well as those at the two other sites. In
      general, it appears that school-based surveys are an effective means of
      monitoring community coverage with ivermectin, rapidly, accurately and at
      relatively low cost. It is therefore recommended that school-based methods of
      monitoring of coverage are adopted by programme managers.

PMID- 16297294
TI  - A simple, artificial-membrane feeding method for the radio-isotope labelling of
      Aedes aegypti polypeptides in vivo.
AB  - An artificial feeding unit has been designed and constructed to feed laboratory
      bred Aedes aegypti with a radio-isotope (35S), so that the mosquitoes'
      polypeptides can be labelled in vivo. In the unit, a piece of Parafilm M barrier
      film is stretched over the bottom, outer surface of a polystyrene Petri dish, to
      create a small gap in which the mixture of blood and radio-isotope is placed.
      Warm water is placed in the dish, to keep the blood at about 37 degrees C. When
      such units were placed on net-covered rearing cages, almost all (80%-90%) of the
      female mosquitoes in the cages took bloodmeals from them. When checked by
      polyacrylamide-gel electrophoresis and autoradiography 1 h after feeding had
      begun, the blood-fed mosquitoes were found to have radio-labelled polypeptides.
      The unit is simple, easy to handle, disposable and can be used to offer small
      blood samples (>or=50 microl) to Ae. aegypti and, presumably, other mosquito
      species.

PMID- 16297296
TI  - Maternal filarial-infection status and its consequences on pregnancy and the
      newborn, in Ragama, Sri Lanka.

PMID- 16297295
TI  - HIV-1 infection, visceral leishmaniasis, Koch's chest and tuberculous meningitis
      in the same patient--a case report.

PMID- 16297297
TI  - Can medical education rise to the challenge of the African crisis?
AB  - In the face of the worsening health crisis in Africa, educationalists there and
      beyond are challenged to identify their role in resolving the crisis. The
      training of doctors has to be re-orientated so that they are well equipped to
      lead the way towards improving the health situation and effectively participating
      in improving the general condition of the people. This can be achieved by medical
      schools having control of their duties and functions and using these powers to
      train doctors who are community-orientated, able to identify clinical and
      epidemiological problems and find suitable solutions. Doctors of the future
      should be comfortable working in the community with other members of health teams
      and confident in addressing all health-related matters in the community. During
      their formative years in medical school they should acquire the skills to
      continue self-education. This paper discusses some of the important steps that
      should be taken by medical schools, taking into account the present situation in
      Africa.

PMID- 16297298
TI  - Body water and plasma volume in severe community-acquired pneumonia: implications
      for fluid therapy.
AB  - OBJECTIVES: To determine changes in total and extracellular body water, plasma
      volume and sodium in children with severe and very severe pneumonia, and examine
      the association between these changes and oxygenation. DESIGN: Prospective,
      observational. SUBJECTS: Fifty children aged 2-59 mths with severe and very
      severe pneumonia. METHODS: Serum sodium (SNa), plasma osmolality (Posm), urinary
      sodium (UNa) and osmolality, total body water (TBW), extracellular water (ECW)
      and plasma volume (PV) were estimated during the acute phase of pneumonia (within
      3-6 hrs of presentation) and after recovery. These were correlated with oxygen
      saturation (SpO(2)) recorded on presentation. RESULTS: All children had cough,
      fever, tachypnoea and chest-wall indrawing; 70% had inability to feed and 90%
      were hypoxaemic (SpO(2) < or = 90%). During the acute phase of illness, among the
      survivors (n=46), mean (SD) ECW and PV were significantly higher than that after
      recovery [ECW 318 (45) vs 308 (49) ml/kg, PV 53.2 (2.3) vs 52.1 (2.3) ml/kg,
      p<0.05]. SNa < or = 135 mmol/L was significantly correlated with ECW and PV
      excess. SpO(2) showed a significant linear relationship with TBW, ECW and PV
      (r=0.43, 0.46 and 0.42, respectively, p<0.005) and SNa (r= or <0.33, p=0.02). On
      multiple regression analysis, ECW, blood urea and PV were significant predictors
      of SpO(2) (combined r=0.63). The four patients who died had significantly higher
      Posm and blood urea and lower SpO(2) but in a logistic regression model SpO(2)
      was the only significant predictor of death (odds ratio 0.54, 95% CI 0.32-0.9,
      p=0.02). CONCLUSION: ECW and PV were moderately increased in severe and very
      severe pneumonia and the increase correlated with better oxygenation. These
      findings suggest that fluid retention in response to hypoxaemia is directed
      towards improving circulating volume. The current practice of fluid restriction
      in hypoxaemic patients with severe pneumonia might be logical only after
      correction of hypoxaemia.

PMID- 16297299
TI  - Comparison between normal saline and a polyelectrolyte solution for fluid
      resuscitation in severely dehydrated infants with acute diarrhoea.
AB  - The optimal intravenous solution for rehydration of infants and children with
      severe dehydration is debated. AIM: The aim was to compare the efficacy of a
      polyelectrolyte solution (group PS) with sodium chloride 0.9% solution (group NS)
      in rapid parenteral rehydration of severely dehydrated infants with acute
      diarrhoea. METHODS: Primary outcomes were volume and time to hydration. Secondary
      outcomes were urea, creatinine, electrolytes, glucose, arterial pH and
      bicarbonate levels. Patients were assigned randomly and openly to one of the two
      treatment groups. Severe dehydration was defined as one or more of the following
      associated with any other sign of dehydration: depressed consciousness, a weak or
      absent pulse or capillary refill time > 10 sec. Peripheral blood samples for
      chemical pathology were collected before and after rapid fluid therapy. The mean
      age of the 36 enrolled infants was 9.1 mths. All had depressed consciousness or
      severe hypotension/shock. The fluid infusion rate was 50 ml/kg/hr until
      haemodynamic stability was restored (absence of severe hypotension and two urine
      emissions). Fluid volume, time to rehydration and weight before and after
      rehydration were recorded. RESULTS: All infants recovered full pulse within 1 hr;
      most had a better level of consciousness or capillary refill <3 sec. Group NS (15
      infants) showed (before and after treatment, respectively) a decrease of plasma
      potassium (3.4 to 3.1 mmol/L, p=0.07), bicarbonate (13.3 to 12.2 mmol/L, p=0.01)
      and glucose (8.2 to 5.8 mmol/L, p<0.01). Group PS (21 infants) showed a decrease
      of potassium (4.4 to 3.2 mmol/L, p<0.01) but an increase in bicarbonate (11.6 to
      13.3 mmol/L, p<0.01) and glucose (11.4 to 14.8 mmol/L, p=0.08). CONCLUSION:
      Polyelectrolyte solution was as effective as normal saline on volume expansion
      and better for correcting acidosis.

PMID- 16297300
TI  - Levels of Th1 and Th2 cytokines in children with post-infectious bronchiolitis
      obliterans.
AB  - BACKGROUND: Post-infectious bronchiolitis obliterans (BO) is a chronic
      obstructive airway disease associated with inflammation and fibrosis of the small
      airways; it is more common in children who have had acute viral bronchiolitis. No
      previous studies have reported the immune response of BO. Unbalanced Th1/Th2
      immune response might be one of the risk factors for developing this illness.
      AIM: To compare the production of interferon (IFN)-gamma, interleukin (IL)-4 and
      IL-10 in peripheral blood mononuclear cell cultures in children with BO and in
      healthy children. METHODS: From March 2003 to October 2003, children with BO and
      healthy children were selected from the paediatric outpatient clinics in our
      centre. Peripheral blood was collected and mononuclear cells were separated and
      cultured (96 hours) with 1% phytohaemagglutinin stimulation. The supernatant was
      stored and cytokine levels were measured through ELISA. RESULTS: IFN-gamma, IL-4
      and IL-10 levels were not significantly different between the groups studied.
      Family history of atopy was significantly associated with subjects with BO
      (p=0.02). CONCLUSIONS: Our results suggest that unbalanced peripheral blood
      Th1/Th2 immune response of children with post-infectious BO might not be
      associated with its pathophysiology. Further studies are required to better
      understand the role of risk factors, including viral genotype, viral load or
      tissue repair abnormalities in the development of post-infectious BO.

PMID- 16297301
TI  - Non-contact infrared thermometry temperature measurement for screening fever in
      children.
AB  - BACKGROUND: During the SARS epidemic, mass fever screening at border control
      points and public hospitals was done by measuring forehead temperature by non
      contact infrared thermometry. However, its accuracy is not well documented.
      METHODS: We evaluated the agreement of non-contact infrared forehead temperature
      (NIFT) measurement by comparing NIFT readings with tympanic temperatures taken in
      children (1 mth to 18 yrs) admitted to the general paediatric wards of Kwong Wah
      Hospital, Hong Kong. RESULTS: A total of 567 patients were recruited and 1000
      pairs of readings were obtained. The incidence of fever, defined as tympanic
      temperature (in rectal model) >38 degrees C (100.4 degrees F), was 12.3%. The
      mean difference between NIFT and tympanic temperature was 2.34 degrees C (4.21
      degrees F) and the 95% limit of agreement between NIFT and tympanic temperature
      was 0.26-4.42 degrees C (0.47-7.96 degrees F). NIFT was significantly lower than
      tympanic temperature readings. The optimal cut-off point of NIFT derived from the
      receiver-operator characteristics curve for fever definition was 35.1 degrees C
      (95.2 degrees F). The sensitivity, specificity, positive predictive value and
      negative predictive value of this cut-off point for fever screening were 89.4%,
      75.4%, 33.7% and 98.1%, respectively. CONCLUSIONS: NIFT measurement has a
      reasonable accuracy in detecting tympanic fever in children. However, one should
      be aware of the high false-positive rate of fever screening using NIFT.

PMID- 16297302
TI  - Urinary tract infections in infants: comparison between those with conjugated vs
      unconjugated hyperbilirubinaemia.
AB  - AIMS: The aim was to investigate conjugated and unconjugated hyperbilirubinaemia
      in association with urinary tract infection (UTI) in young infants. METHODS:
      Fifty infants aged <3 mths who developed prolonged jaundice among 2128 infants
      with UTI from 1984 to 2004 were enrolled retrospectively. They were divided into
      conjugated (n=22) and unconjugated (n=28) hyperbilirubinaemia groups and the
      clinical variables between the two were compared. RESULTS: Compared with the
      unconjugated group, the conjugated hyperbilirubinaemia group had statistically
      significantly lower haemoglobin (1.57 vs 1.80 micromol/L), higher aspartate
      aminotransferase (96 vs 32.5 U/L) and alanine aminotransferase (81.5 vs 16 U/L),
      were older on admission (48.0 vs 32.5 days), had a longer duration of jaundice
      before treatment (43.5 vs 30 days) and a higher incidence of E. coli infections
      (19/22 vs 15/28). The direct/total bilirubin ratio was linearly correlated with
      duration of jaundice before treatment (p=0.004). The most significant cut-off
      value for the duration of jaundice vis-a-vis the type of jaundice was 38 days
      (p=0.007). Patients who on presentation had had jaundice for >44 days (p=0.007)
      were unlikely to have unconjugated hyperbilirubinaemia. CONCLUSIONS: Infants with
      UTI may present with unconjugated hyperbilirubinaemia in the early stage. After 6
      weeks, it is always conjugated hyperbilirubinaemia and is frequently associated
      with anaemia, elevated hepatic aminotransferases and E. coli infections.

PMID- 16297303
TI  - Home and community management of acute respiratory infections in children in
      eight Ugandan districts.
AB  - BACKGROUND: Acute respiratory infections (ARI), especially pneumonia, are the
      second largest child killer in sub-Saharan Africa. Symptoms, including cough and
      difficult/rapid breathing, frequently overlap those of malaria. In Uganda, the
      Home-Based Management (HBM) strategy treats all childhood fevers as malaria in
      the community, ignoring the pneumonia symptom overlap. AIM: To determine the
      extent of overlap of fever and ARI symptoms at community level, the timeliness of
      care-seeking and the treatments sought for ARI with or without fever. METHODS:
      From eight districts, 3223 households with 3249 children aged <2 years were
      randomly selected through two-stage cluster sampling and their primary caretakers
      were interviewed regarding the child's most recent illness episode using 2-week
      recall. RESULTS: Of the 1682 children <2 years who had been sick, 19% reported
      overlapping symptoms of fever, cough and "difficult/rapid breathing". Of these,
      45% were given antimalarials alone. Use of health facilities was low and 42% of
      antibiotics used were obtained from drug shops or home-stocks. CONCLUSIONS: Given
      the large overlap of fever and ARI symptoms and the reported practice of using
      primarily antimalarials, the implications of HBM might be the continued or
      increased mismanagement of pneumonia. Community drug distributors' ability to
      identify rapid breathing and make a presumptive diagnosis of pneumonia based on
      respiratory rate should be tested.

PMID- 16297304
TI  - Neonatal sepsis in Jamaican neonates.
AB  - AIM: To determine the incidence and causative organisms of bacterial sepsis in
      neonates at The University Hospital of the West Indies. METHODS: A retrospective
      review of all neonates with culture-proven sepsis admitted to the hospital
      between January 1995 and December 2000 was conducted. Incidence rates and
      antimicrobial susceptibility patterns were determined. RESULTS: There were 4702
      admissions to the neonatal unit during the study period. Of these, 135 had
      culture-proven sepsis and 115 were inborn, giving an incidence of 6.7/1000 live
      births. There were 89 positive blood cultures, 51 positive urine cultures and two
      positive CSF cultures. The single most common organism was Klebsiella spp (28%).
      Other organisms included Escherichia coli (16%), group B Streptococcus (11%) and
      Enterobacter spp (10%). The aminoglycoside resistance rate of Klebsiella spp was
      46% and seven isolates had multiple resistance to antibiotics. There was a case
      fatality rate of 6.7%. CONCLUSION: Physicians involved in newborn care at The
      University Hospital of the West Indies need to recognise the important role
      Klebsiella now plays in neonatal sepsis and its contribution to neonatal
      mortality. Empirical antibiotic regimens for gram-negative sepsis must take into
      consideration the high rates of aminoglycoside resistance that are now prevalent.

PMID- 16297305
TI  - Cerebral salt wasting in tuberculous meningitis: treatment with fludrocortisone.
AB  - Three cases of cerebral salt wasting complicating tuberculous meningitis are
      described. Diagnosis was based on hyponatraemia associated with high urinary
      sodium excretion and inappropriately high urine output in the presence of
      dehydration. Treatment with fludrocortisone resulted in sodium and fluid
      homeostasis.

PMID- 16297306
TI  - Calcium and phosphate levels in Nigerian children with malaria.
AB  - Calcium and phosphate levels were investigated in 39 children with malaria (six
      severe and 33 uncomplicated) and in 39 healthy children. Hypocalcaemia (calcium
      <2.13 mmol/L, adjusted for albumin level) was detected in 23.1% of malaria cases
      and in 5.1% of controls, and hypophosphataemia (<1 mmol/L) in 38.5% of cases and
      in 15.4% of controls. Mean (SD) calcium levels in cases [2.26 (0/15)] were
      similar to those in controls [2.24 (0.12)]. In Nigerian children, hypocalcaemia
      and hypophosphataemia are associated with malaria.

PMID- 16297308
TI  - Thankfully, some things never change.

PMID- 16297309
TI  - Sodium bicarbonate and hydrogen peroxide: the effect on the growth of
      Streptococcus mutans.
AB  - PURPOSE: This in vitro experiment studied the effects of sodium bicarbonate and
      hydrogen peroxide on the cariogenic bacteria Streptococcus mutans through
      analysis with a spectrophotometer. METHODS: The growth of S. mutans was analyzed
      using seven different environments. Twelve wells in each of the seven rows of a
      multi-well plate were used to incubate the test materials. In combinations of 10
      microl distilled water, 100 microl broth, 10 microl 10% sucrose, 10 microl S.
      mutans, 10 microl 10% sodium bicarbonate, and 10 microl 3% hydrogen peroxide,
      seven different environments were created for testing. Environments had either
      sodium bicarbonate or hydrogen peroxide with S. mutans, or a combination of
      sodium bicarbonate and hydrogen peroxide with S. mutans. The plate was incubated
      at 37 degrees C and measured at 0, 18, 20, 22, 24, 26, 28, 30, and 42 hours by
      optical density with a spectrophotometer. RESULTS: Results showed bacterial
      growth was prevented by sodium bicarbonate, hydrogen peroxide, and the
      combination of sodium bicarbonate and hydrogen peroxide. Although hydrogen
      peroxide is bacteriocidal and sodium bicarbonate is bacteriostatic, there were no
      significant differences among the three treatment groups in spectrophotometer
      readings at any of the nine readings over 42 hours. CONCLUSION: There was no
      significant difference among the effects of hydrogen peroxide, sodium
      bicarbonate, or the sodium bicarbonate and hydrogen peroxide combination, as
      measured by optical density. The hydrogen peroxide, sodium bicarbonate, and the
      sodium bicarbonate and hydrogen peroxide combination prevented bacterial growth
      of S. mutans. The results show that products containing these agents have the
      ability to stop the growth of S. mutans. Products containing sodium bicarbonate
      and/or hydrogen peroxide may be useful to caries-prone patients. More studies are
      needed to confirm these results on patients.

PMID- 16297310
TI  - Assessment of the alveolar bone surrounding the mandibular anterior teeth of
      individuals wearing a tongue stud.
AB  - PURPOSE: One of the latest trends in ornamental body piercing focuses on the oral
      cavity, with the most common piercing site being the tongue. Oral health care
      professionals are anecdotally reporting the incidence of radiographically
      detectable alveolar bone abnormalities surrounding the mandibular anterior teeth
      in patients who wear tongue studs. This research study was conducted to assess
      the frequency and extent of bone abnormalities in the supporting alveolar bone
      adjacent to the mandibular anterior teeth in individuals wearing tongue studs.
      METHODS: With the use of convenience sampling, periapical radiographs were taken
      of the mandibular anterior teeth of individuals wearing tongue studs and compared
      to the radiographs of individuals who had never worn tongue studs (N = 46).
      Additionally, a self-report questionnaire was used to gather demographic data on
      participants and specific information related to their piercings. A periodontist
      conducted blind evaluations of the radiographs. RESULTS: With an alpha level of
      .05, a one-tailed t test indicated a significant difference between the two
      groups, t44 = 1.902, P = .032. However, the correlation coefficient comparing
      length of time to presence of alveolar bone abnormalities was 0.216, indicating a
      weak relationship between the amount of time that the tongue stud had been worn
      and the development of abnormalities in the alveolar bone. CONCLUSION: These
      findings indicate that individuals wearing a tongue stud for any length of time
      are at risk for developing abnormalities in the alveolar bone surrounding the
      mandibular anterior teeth.

PMID- 16297311
TI  - Development and evaluation of a tobacco cessation motivational program for
      adolescents based on physical attractiveness and oral health.
AB  - PURPOSE: Little is known about how to motivate youth to participate in smoking
      cessation programs. This paper reports an investigation of the feasibility and
      acceptability of an intervention that used vanity and oral health issues
      associated with tobacco use to motivate adolescent tobacco users to enter a
      school-based tobacco cessation program. METHODS AND MATERIALS: Sixty-four
      continuation high school students aged 14 to 19 (31% female) and living in rural
      California participated in a youth-oriented, vanity and oral health-focused
      intervention designed to motivate tobacco users to join a six-week tobacco
      cessation group. RESULTS: Following the intervention, 21 of 37 (57%) regular
      smokers signed up for the cessation program. Of these smokers, seven (33%) did
      not indicate on the baseline questionnaire any desire to quit smoking. Of the 21
      smokers who signed up to participate in the cessation program, 16 (76%) actually
      participated (10 males and six females), eight (50%) completed all treatment
      sessions, and four (25%) reported that they quit smoking at the end of the
      program. CONCLUSIONS: Overall program evaluations were very favorable. Findings
      were interpreted to provide support for the feasibility and acceptability of
      using physical appearance and oral health-oriented programs to motivate
      adolescent tobacco users to enter school-based cessation programs. Further study
      is needed to determine the effectiveness of such programs.

PMID- 16297313
TI  - [From "bacterial-toxin treated simultaneously" to "four syndromes and four
      methods"--improvement and integration of the syndrome-differentiating thinking
      for treating multiple organ dysfunction syndrome with integrated traditional
      Chinese and western medicine].

PMID- 16297312
TI  - The utilization of dental hygiene students in school-based dental sealant
      programs.
AB  - Early detection of childhood caries is important to childrens' overall health.
      Untreated childhood caries can lead to pain, as in abscesses from prolonged
      neglect; altered dietary intake; and delays in the development of the permanent
      teeth if the primary teeth are prematurely lost. In the summer of 2000, funds
      were provided to various oral health care provider organizations by the Illinois
      Department of Public Health, Division of Oral Health, to purchase portable
      equipment to deliver preventive services (i.e., exams, sealants, and oral hygiene
      education) to second-grade and sixth-grade children who qualified for Medicaid
      and/or free and reduced-cost lunch programs. The Dental Sealant Grant Program at
      Southern Illinois University in Carbondale was a unique program that utilized
      dental hygiene students as the primary human resource. Within the state, the
      Dental Sealant Grant Program was, at the time of this report, the only grantee
      sponsored by a stand-alone dental hygiene program (not affiliated with a dental
      school). Other positive aspects of the dental hygiene-sponsored sealant program
      were that the supervising dentist was the primary Medicaid provider and a member
      of the dental hygiene faculty; dental hygiene faculty participated actively as
      site coordinators and clinicians; and dental hygiene students were given the
      opportunity to volunteer for the program as a service-learning option.

PMID- 16297314
TI  - [Effect of heat shock protein 70 on nuclear factor-KappaB/inhibitor protein-alpha
      of nuclear factor-KappaB in brain edema induced by infection in rat].
AB  - OBJECTIVE: To study the effect of heat shock protein 70 (HSP70) on activation of
      nuclear factor-KappaB (NF-KappaB) and degradation of inhibitor KappaB-alpha
      protein (I-Kappa B alpha) in brain edema induced by Pertussis bacilli infection
      in rats. METHODS: Brain edema was induced by injection of Pertussis bacilli
      suspension via the left internal carotid artery. Seventy-two Sprague-Dawley rats
      were divided randomly into brain edema group, pretreatment with heat shock group,
      and normal saline control group. The rats were sacrificed 4, 8 and 24 hours after
      injection of Pertussis bacilli and normal saline, respectively. HSP70 expression
      and the degradation of I-Kappa B alpha were assayed in all animals with Western
      blot analysis. Electrophoretic mobility shift assay (EMSA) was performed to
      assess NF-KappaB activation of nuclear extract of neurones. RESULTS: The results
      showed that HSP70 expression was significantly increased in heat shock group
      compared with control group and brain edema group. The activity of NF-KappaB
      started to increase at 2 hours in brain edema group and peaked at 24 hours. The
      expression of I-Kappa B alpha began to decrease at 2 hours and reached the lowest
      level at 24 hours. In heat shock group the activity of NF-KappaB complexes was
      lower than that in brain edema group, and the expression of I-Kappa B alpha
      higher than that in brain edema group at corresponding time points. CONCLUSION:
      HSP70 shows a protective effect on development of brain edema as its expression
      increases. The mechanism might be associated with its inhibitory effect on
      degradation of I-Kappa B alpha and activation of NF-KappaB.

PMID- 16297316
TI  - [Changes in glucocorticoid receptor and heat shock protein 70 in liver tissue
      after trauma with hemorrhagic shock in rats].
AB  - OBJECTIVE: To investigate changes and functions of glucocorticoid (GR) and heat
      shock protein 70 (HSP70) at the level of cellular receptor in liver in
      hemorrhagic shock after trauma. METHODS: Adult Wistar rats were used and a rat
      model of shock was reproduced by hemorrhaging accompanied by bilateral femur
      fracture. Changes in hepatic tissue GR, HSP70, pathology of liver, hepatic
      function markers in serum were dynamically observed. The expression of GR and
      HSP70 in hepatic tissue was assayed by Western blot and then analyzed with
      computer imaging system. RESULTS: Protein content of GR gradually decreased in
      hepatic tissue after trauma, reduced to the nadir at 6 hours after trauma, and it
      was decreased even more when trauma was added to bleeding. Protein content of
      HSP70 was gradually increased in hepatic tissue after severe trauma, peaking at 6
      hours after trauma, and it maintained at a rather high level at 8 hours after
      trauma. It was even more increased in when hemorrhagic shock was followed by
      trauma. Alterations in hepatic function markers and pathology were not obvious
      after simple trauma. But after trauma was added to hemorrhagic shock, significant
      increase in alanine aminotransferase (ALT) and total bilirubin (TB) in serum was
      noted at 4 and 2 hours after trauma respectively (all P<0.01), and albumin
      content was obviously decreased (P<0.01). There were more inflammatory cell
      infiltrations in hepatic sinusoids at 6 hours after trauma. CONCLUSION: GR may
      play an important role in anti-injury mechanism of hepatic tissue cell after
      trauma with hemorrhagic shock. HSP70 may participate in initiating anti-injury
      mechanism of hepatic cells.

PMID- 16297315
TI  - [Changes in sensitivity of vascular smooth muscle to calcium and its role in the
      biphasic change in vascular reactivity following hemorrhagic shock in rats].
AB  - OBJECTIVE: To observe the change in sensitivity of vascular smooth muscle to
      calcium and its role in biphasic vascular reactivity following hemorrhagic shock
      (HS) in rats. METHODS: The superior mesenteric artery (SMA) obtained from rats
      with HS was used to assay the vascular reactivity and sensitivity to calcium by
      observing the contraction initiated by norepinephrine (NE) and Ca(2+) under
      depolarizing conditions (120 mmol/L K(+)) with isolated organ perfusion system.
      At different time points after shock, the relationship between vascular
      reactivity and sensitivity to calcium was analyzed. Meanwhile the effects of the
      angiotensin II (Ang II) and insulin, the calcium sensitivity regulating agents,
      on vascular reactivity were also observed. RESULTS: As compared with the control
      group, the cumulative dose-response curves of SMA to NE and Ca(2+) at early shock
      stages, i.e. immediately and 30 minutes after shock, shifted to the left, the
      maximal contractions (Emax) of NE and Ca(2+) were increased significantly (P<0.05
      or P<0.01). But the cumulative dose-response curves of SMA to NE and Ca(2+) at
      late shock stage shifted to the right, and Emax of NE and Ca(2+) were
      significantly decreased (P<0.05 or P<0.01). Ang II increased the contractile
      response of SMA to NE and Ca(2+) when shock persisted for 2 hours, rendering the
      cumulative dose-response curves of NE and Ca(2+) shifted to the left (P<0.05 or
      P<0.01). But insulin decreased the contractile response of SMA to NE and Ca(2+)
      at early stage of shock, rendering the cumulative dose-response curves of NE and
      Ca(2+) shifted to the right (P<0.05 or P<0.01). CONCLUSION: Sensitivity of
      vascular smooth muscle to calcium following hemorrhagic displays a biphasic
      change. It plays important roles in biphasic vascular reactivity.

PMID- 16297317
TI  - [Relationship of changes in basement membrane of microvessels after cerebral
      ischemia/reperfusion and plasminogen activator system in aged rats].
AB  - OBJECTIVE: To study the relationship of changes in basement membrane of cerebral
      micro-vessels and plasminogen activator system after cerebral
      ischemia/reperfusion (I/R) injury in aged rats. METHODS: Middle cerebral artery
      occlusion (MCAO) was produced by the introduction of a thread. Rats were divided
      randomly into sham-operation group with young rats (cerebral ischemia 3 hours and
      I/R 6, 12, 24, 72, 144 hours groups), sham-operation group and I/R groups in aged
      rats (cerebral ischemia 3 hours and I/R 6, 12, 24, 72, 144 hours groups).
      Immunohistochemical technique, zymogram analysis, and reverse zymogram analysis
      were used to study changes in basement membrane structure of cerebral-cortex
      microvessel, type IV collagen (Col IV) and laminin (LN) contents, and plasminogen
      activator system in every group. RESULTS: With the increase of age, Col IV and LN
      contents of the microvessel basement membrane increased. With prolongation of
      I/R, the contents of Col IV and LN decreased in both young and aged rats, while
      the contents of tissue plasminogen activator (t-PA), urokinase plasminogen (u-PA)
      and plasminogen activator inhibitor (PAI-1) expression increased at the beginning
      and decreased subsequently. Compared with young groups, Col IV (ischemia 3 hours
      I/R 12 hours), LN (ischemia 3 hours-I/R 24 hours), t-PA (I/R 6-24 hours) and u-PA
      (I/R 12-144 hours) expression levels were higher in aged rats, but PAI-1 (I/R 12
      and 24 hours) expression was lower. In addition, changes in PAI-1 contents as
      determined with reverse zymogram analysis method coincided with its
      immunoexpression. CONCLUSION: With the increase of age, alterations in
      constituents of cerebro-microvessel basement membrane (Col IV and LN) increased.
      Injury to cerebro-microvessel basement membrane resulted in more serious changes
      in aged rats compared with the young rats. Changes in cerebro-microvessel
      basement membrane after I/R injury in the aged SD rats is related to change in
      plasminogen activator system.

PMID- 16297318
TI  - [Effects of moderate hypothermia on expression of nuclear factor-KappaB in rats
      with acute pancreatitis].
AB  - OBJECTIVE: To observe the dynamic changes in the DNA binding activity of nuclear
      factor-KappaB (NF-KappaB) in rat pancreatic and lung tissues in acute hemorrhagic
      necrotizing pancreatitis (AHNP), and investigate the effects of moderate
      hypothermia on AHNP-induced NF-KappaB binding activity in a time-dependent
      fashion. METHODS: A group of 24 rats was randomly divided into control group, 2,
      5 or 12 hours groups after reproduction of AHNP. NF-KappaB binding activity in
      pancreas and lung tissues was determined using electrophoretic mobility shift
      assay (EMSA). In another group of 36 rats were randomized into three groups with
      equal number: sham-operated rats which were kept under 37-37.5 degrees C after
      laparotomy; AHNP rats with normothermia (37-37.5 degrees C); AHNP rats with
      moderate hypothermia (32-33 degrees C). Activity of NF-KappaB was assessed at 2
      or 5 hours after reproduction of pancreatitis. RESULTS: DNA binding activity of
      NF-KappaB in pancreas and lung tissue of AHNP rats gradually increased after the
      development of pancreatitis, and NF-KappaB binding activity was more prominent in
      pancreas than that in lung tissue at each time point (all P<0.01). NF-KappaB
      binding activity was inhibited at 2 and 5 hours of moderate hypothermia in lung
      tissue (P<0.01), but there was no difference in pancreatic tissue between
      normothermic and hypothermic rats at each time point. CONCLUSION: These data
      suggest that the expression of NF-KappaB is significantly increased after the
      development of AHNP. Moderate hypothermia could inhibit the expression of NF
      KappaB in lung tissue in acute pancreatitis.

PMID- 16297319
TI  - [Effect of losartan on expression of Janus kinase 2 and signal transducer and
      activator of transcription 3 in glomeruli of diabetic rats].
AB  - OBJECTIVE: To investigate the effects of losartan on Janus kinase 2 (JAK2) and
      signal transducer and activator of transcription 3 in glomeruli of diabetic rats.
      METHODS: Sixty Wistar male rats were randomly divided into control group (n=20),
      diabetes group (n=20), and losartan treatment group (n=20). Diabetes was induced
      by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg). Losartan (10
      mg/kg) was administered daily by gavage from the day following the induction of
      diabetes. The animals were sacrificed in the weeks 2 and 4 after STZ injection.
      The renal cortical tissues were obtained and glomeruli were isolated. The protein
      expressions of JAK2, STAT3 and tyrosine phosphorylated STAT3 (p-STAT3) were
      assessed respectively by Western blot. Immunoprecipitation and Western blot
      analysis were used to determine tyrosine phosphorylated JAK2 (p-JAK2). JAK2 and
      STAT3 mRNA were assayed by reverse transcription-polymerase chain reaction (RT
      PCR). RESULTS: Compared with the control group rats, the respective expression of
      JAK2, p-JAK2, STAT3, p-STAT3, JAK2 mRNA and STAT3 mRNA was significantly
      increased in the diabetic glomeruli without losartan treatment (all P<0.01).
      After treatment with losartan, the expression of p-JAK2 and p-STAT3 in the
      diabetic glomeruli was down-regulated (all P<0.05). However losartan had no
      effect on the expression of JAK2, STAT3, JAK2 mRNA and STAT3 mRNA in the diabetic
      glomeruli. CONCLUSION: JAK2 and STAT3 signal proteins may be involved in the
      kidney damage associated with diabetes. Regulation of phosphorylation of JAK2 and
      STAT3 may be responsible for the renal protective effects of losartan in diabetic
      rats.

PMID- 16297321
TI  - [Relationship between different renal functional state with therapeutic effect on
      diabetic foot ulcers].
AB  - OBJECTIVE: To study the relationship between renal functional state and the
      therapeutic effect and prognosis of foot ulcers in the patients with diabetic
      mellitus. METHODS: The renal function was evaluated in term of glomerular
      filtration rate, microalbuminuria, proteinuria, blood urea nitrogen (BUN) and
      creatinine (Cr) levels in 126 patients with I-V class diabetic foot ulcers
      (according to Wagner classic standard) before the treatment, and then these
      patients were divided into 1-5 classes (according to Mogenson standard) and given
      systemic treatment and local debridement, with astragalus for topical
      application. The time of growth of granulation tissue (GT), the time of healing
      (HT), the amputation rate and mortality were observed. RESULTS: GT and HT of
      ulcer prolonged with worsening of diabetic nephropathy regardless of the disease
      phase of foot ulcers, especially the GT and HT of foot ulcers were significantly
      longer in IV and V phases of diabetic nephropathy than those of III phase
      diabetic nephropathy though the conditions of their foot ulcers were about the
      same. GT and HT in all the patients with the foot ulcers in the similar condition
      exhibited significantly positive linear correlation with the severity of diabetic
      nephropathy (r(1)=2.344 and r(2)=2.563, respectively, both P<0.05). The mortality
      of I-III phase diabetic nephropathy was significantly lower than that of IV and V
      phase diabetic nephropathy when the foot ulcers of these patients were of the
      same extent (P<0.05). CONCLUSION: A worsening of renal function would affect the
      treatment effect and prognosis of foot ulcers in the patients with diabetic foot
      ulcers, implicating that it is very important to improve the renal function in
      the treatment of patients with diabetic foot ulcers.

PMID- 16297323
TI  - [Protective effect of reduced glutathione on multiple organ function in patient
      with acute pancreatitis].
AB  - OBJECTIVE: To study the protective effect of reduced glutathione (GSH) on
      multiple organ function in patient with acute pancreatitis. METHODS: A total of
      45 patients with acute pancreatitis was randomly divided into two groups, 22
      patients were given GSH in a dose of 1.2 g/d through intravenous drip for 7 days
      as GSH group, and 23 patients were not given GSH to serve as control group. The
      same treatment was given to both groups other than GSH. Plasma contents of tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and biochemistry
      indexes were determined. RESULTS: After the treatment, the levels of TNF-alpha
      and IL-6 were significantly decreased in both groups (all P<0.05). The levels of
      TNF-alpha and IL-6 were decreased much more obviously in GSH group compared with
      those in control group (P<0.05). Plasma alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), creatinine (Cr), blood urea nitrogen (BUN), lactate
      dehydrogenase (LDH), creatine kinase (CK), and MB isoenzyme of creatine kinase
      (CK-MB) were significantly decreased in both treatment groups, but the decrease
      of all these indexes was more marked in GSH group (P<0.05). CONCLUSION: The
      results suggest that GSH has beneficial effects in protecting visceral organ
      function in patients with acute pancreatitis.

PMID- 16297324
TI  - [Tubular epithelial-myofibroblast transdifferentiation and expressions of
      hepatocyte growth factor and Smad7 in renal tissues of rat with experimental
      diabetes].
AB  - OBJECTIVE: To investigate the relationship of tubular epithelial-myofibroblast
      transdifferentiation and the expressions of hepatocyte growth factor (HGF) and
      Smad7, and to elucidate the role of HGF and Smad7 in diabetic nephropathy.
      METHODS: Diabetes was induced in male Wistar rats with right nephrectomy and
      streptozotocin (STZ) administration. The expressions of cytokeratin 18 (CK18),
      alpha-smooth muscle actin (alpha-SMA), HGF and Smad7 were assayed with
      immunohistochemistry. The expressions of alpha-SMA, HGF were assayed with flow
      cytometry. The expression of Smad7 was assessed by Western blot. RESULTS:
      Compared with those in kidneys of the control group, diabetic kidneys showed down
      regulated expression of CK18 and up-regulated expression of alpha-SMA. The
      expressions of HGF and Smad7 were increased significantly in the kidneys of
      diabetic rats at first, then they decreased gradually, but were still higher than
      those of control. CONCLUSION: The tubular epithelial cells may undergo phenotypic
      alterations and change to myofibroblasts. The absence of up-regulation of HGF and
      Smad7 may be related with the transdifferentiation of tubular cells in this
      animal model.

PMID- 16297322
TI  - [Study of effects of drugs on myocardial hypertrophy due to overload].
AB  - OBJECTIVE: To study the relation of expression change of tumor necrosis factor
      alpha (TNF-alpha), angiotensin II (Ang II), and endothelin-1 (ET-1), and the
      effect of imidapril on myocardial hypertrophy due to overload. METHODS: Sixty
      three rats were randomly divided into four groups: sham operation (n=15),
      overload group (n=16), imidapril group (n=16), and Caweidiluo group (n=16).
      Hypertrophic myocardium was reproduced in rats by constricting abdominal aorta.
      Blood samples and heart were harvested 12 weeks after aorta constriction, and
      myocardial hypertrophy index, the contents of Ang II, ET-1 in the myocardium and
      plasma were determined by radioimmunoassay and TNF-alpha in the myocardium and
      plasma were determined by enzyme linked immunoadsorbent assay. RESULTS: Left
      ventricle showed obvious hypertrophy 12 weeks after operation. The contents of
      TNF-alpha, Ang II and ET-1 in the myocardium, and the content of TNF-alpha in
      serum, Ang II and ET-1 in plasma were increased compared with those of controls
      (all P<0.01). The treatment of imidapril and Caweidiluo could restrain the
      development of left ventricle hypertrophy after operation, and imidapril
      decreased the contents of TNF-alpha, Ang II and ET-1 in myocardium compared with
      overload group (all P<0.01). Imidapril lowered the contents of TNF-alpha in
      serum, Ang II and ET-1 in plasma, compared with overload group (all P<0.01), but
      not ET-1. Caweidiluo lowered the contents of TNF-alpha, Ang II and ET-1 in
      myocardium, the contents of TNF-alpha in serum, Ang II and ET-1 in plasma (all
      P<0.01) compared with overload group (both P<0.01). CONCLUSION: The activation of
      rennin-angiotensin system (RAS) by over load results to an elevation of TNF-alpha
      contents in plasma and myocardium, and it is probably one of the major regulatory
      pathways of myocardial hypertrophy.

PMID- 16297326
TI  - [Effects of different levels of positive end expiratory pressure on lung
      recruitment and hemodynamics after sustained inflation in acute respiratory
      distress syndrome in sheep].
AB  - OBJECTIVE: To study the effects of different levels of positive end expiratory
      pressure (PEEP) on recruitment and hemodynamics after sustained inflation in
      acute respiratory distress syndrome (ARDS) in sheep. METHODS: Twelve adult sheep
      were anaesthetized and ARDS was induced by lung lavage with warm normal saline.
      Pressure-volume (P-V) curves were traced using the low flow technique and the
      upper inflection point (UIP) was determined. Sustained inflation was exercised at
      the pressure of 5 cm H(2)O (1 cm H(2)O=0.098 kPa) below UIP, and the sheep were
      divided into groups according to different PEEP levels (PEEP5, PEEP10, PEEP15,
      PEEP20). Hemodynamics and lung mechanics values were recorded during the 2 hours
      of recruitment, and biopsy was performed at the end of the trial. RESULTS: There
      was no effect on hemodynamics and recruitment in 2 hours in PEEP5 and PEEP10
      groups, but oxygenation was found to be decreased in PEEP5 group, and focal
      alveolar collapse was found in pathological examination. When the PEEP level
      reached 15 cm H(2)O, there was significant elevation in central venous pressure
      (CVP), and cardiac index (CI) fell remarkably, but oxygenation index and lung
      mechanics were improved and stable in 2 hours. CONCLUSION: Our study demonstrates
      that it can obviously improve oxygenation when PEEP is set at 10-20 cm H(2)O,
      oxygenation can be obviously improved, with little disturbance to hemodynamics in
      case cardiac function is normal.

PMID- 16297327
TI  - [Establishment of a mathematical model of static pressure-volume curve in acute
      respiratory distress syndrome].
AB  - OBJECTIVE: To explore the use of second derivate in seeking the inflection points
      of pressure-volume (P-V) curves and compare it with the step-by-step regression
      method. METHODS: Under general anesthesia, tracheotomy was done in 6 adult sheep,
      warm physiological saline was used to lavage the respiratory, followed by
      alveolar lavaged via tract through bronchofiberscope to reproduce acute
      respiratory distress syndrome (ARDS). The low flow technique was used to trace
      the P-V curves before and after the saline lavage, and features of the curves
      were analyzed with the software of Findgraph. RESULTS: The above two methods fit
      the P-V data well with good accuracy both in inflation and deflation limbs in
      normal and ARDS animals. From the graph of second derivate, the characteristic
      points of the P-V curves could be exactly obtained, and the low inflection points
      obtained by this method were well correlated with lower inflection point (LIP) +2
      cm H(2)O (1 cm H(2)O=0.098 kPa) obtained by step-by-step regression method.
      CONCLUSION: The graph of second derivate gained from P-V curves is useful to
      describe the inflection points, so that it can be helpful in instructing in
      setting the required parameters of the ventilator in the treatment of ARDS.

PMID- 16297338
TI  - Molecular mechanisms regulating expression and function of transcription
      regulator inhibitor of differentiation 3.
AB  - The transcription factor antagonist inhibitor of differentiation 3 (Id3) has been
      implicated in many diverse developmental, physiological and pathophysiological
      processes. Its expression and function is subjected to many levels of complex
      regulation. This review summarizes the current understanding of these mechanisms
      and describes how they might be related to the diverse functions that have been
      attributed to the Id3 protein. Detailed understanding of these mechanisms should
      provide insights towards the development of therapeutic approaches to various
      diseases, including cancer and atherogenesis.

PMID- 16297339
TI  - Molecular mechanism and regulation of autophagy.
AB  - Autophagy is a major cellular pathway for the degradation of long-lived proteins
      and cytoplasmic organelles in eukaryotic cells. A large number of
      intracellular/extracellular stimuli, including amino acid starvation and invasion
      of microorganisms, are able to induce the autophagic response in cells. The
      discovery of the ATG genes in yeast has greatly advanced our understanding of the
      molecular mechanisms participating in autophagy and the genes involved in
      regulating the autophagic pathway. Many yeast genes have mammalian homologs,
      suggesting that the basic machinery for autophagy has been evolutionarily
      conserved along the eukaryotic phylum. The regulation of autophagy is a very
      complex process. Many signaling pathways, including target of rapamycin (TOR) or
      mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase-I (PI3K
      I)/PKB, GTPases, calcium and protein synthesis all play important roles in
      regulating autophagy. The molecular mechanisms and regulation of autophagy are
      discussed in this review.

PMID- 16297340
TI  - Two ligands for a GPCR, proton vs lysolipid.
AB  - Recently, two different chemicals have been matched as ligands with the same G
      protein-coupled receptor (GPCR). Double-pairing of OGR1 family GPCRs with proton
      and lysolipid raises several questions. First, whether both are the real ligands
      for the GPCRs. Second, whether modulation of a GPCR by two chemicals could be
      possible. Third, one of the chemicals is proton. Proton-sensing not only is a new
      action mode of GPCR activation, but also it could be generalized in other GPCRs.
      In this review, I would like to summarize the issue and discuss questions with
      pharmacological criteria.

PMID- 16297341
TI  - Differential sensitivity of GABAergic and glycinergic inputs to orexin-A in
      preganglionic cardiac vagal neurons of newborn rats.
AB  - AIM: To test the effect of orexin-A (hypocretin-1), a neuropeptide synthesized in
      the lateral hypothalamus and the perifornical area, on the glycinergic inputs and
      the GABAergic inputs of cardiac vagal neurons (CVN). METHODS: The effects of
      orexin-A at three concentrations (20 nmol/L, 100 nmol/L, 500 nmol/L) on the
      glycinergic inputs and the GABAergic inputs were investigated by using retrograde
      fluorescent labeling of cardiac neurons (CVN) in the nucleus ambiguus (NA) and
      the voltage patch-clamp technique. RESULTS: Orexin-A dose-dependently increased
      the frequency of both the glycinergic and the GABAergic spontaneous inhibitory
      postsynaptic currents (sIPSC). However, at a lower concentration (20 nmol/L) of
      orexin-A, although the frequency of the glycinergic sIPSC was significantly
      increased, the frequency of the GABAergic sIPSC was not significantly changed.
      CONCLUSION: The glycinergic inputs and the GABAergic inputs have different
      sensitivities to orexin-A, which suggests that the two kinds of inhibitory inputs
      might play different roles in the synaptic control of cardiac vagal functions.

PMID- 16297342
TI  - Histamine ameliorates spatial memory deficits induced by MK-801 infusion into
      ventral hippocampus as evaluated by radial maze task in rats.
AB  - AIM: To investigate the role of histamine in memory deficits induced by MK-801
      infusion into the ventral hippocampus in rats. METHODS: An 8-arm radial maze (4
      arms baited) was used to assess spatial memory. RESULTS: Bilateral ventral
      intrahippocampal (ih) infusion of MK-801 (0.3 microg/site), an N-methyl-D
      aspartate (NMDA) antagonist, impaired the retrieval process in both working
      memory and reference memory. Intrahippocampal injection of histamine (25 or 50
      ng/site) or intraperitoneal (ip) injection of histidine (25, 50 or 100 mg/kg)
      markedly ameliorated the spatial memory deficits induced by MK-801. Both the
      histamine H1 antagonist pyrilamine (0.5 or 1.0 microg/site, ih) and the H2
      antagonist cimetidine (2.5 microg/site, ih) abolished the ameliorating effect of
      histidine (100 mg/kg, ip) on reference memory deficits, but not that on working
      memory deficits induced by MK-801. CONCLUSION: The results indicate that
      histamine in the ventral hippocampus can ameliorate MK-801-induced spatial memory
      deficits, and that histamine's effect on reference memory is mediated by
      postsynaptic histamine H1 and H2 receptors.

PMID- 16297343
TI  - Neuroprotective effects of scutellarin on rat neuronal damage induced by cerebral
      ischemia/reperfusion.
AB  - AIM: To investigate the neuroprotective effect and mechanisms of scutellarin, a
      flavonoid extracted from Erigeron breviscapus Hand Mazz, against neuronal damage
      following cerebral ischemia/reperfusion. METHODS: Rats were pretreated ig with
      scutellarin for 7 d and then subjected to cerebral ischemia/reperfusion (I/R)
      injury induced by a middle cerebral artery occlusion (MCAO). The infarct volume
      and neurological deficit were determined by TTC staining and Longa's score. The
      permeability of the blood-brain barrier was evaluated by measurement of the Evans
      blue (EB) content in the brain with a spectrophotometer. The total NOx content
      was determined. Nitric oxide synthase (NOS) isoforms (iNOS, eNOS, nNOS) and the
      key angiogenic molecules, vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (bFGF), were detected by Western blotting. RESULTS:
      Scutellarin significantly reduced infarct volume (P<0.05 or P<0.01), ameliorated
      the neurological deficit and reduced the permeability of the blood-brain barrier
      (BBB) (P<0.05). When rats were pretreated with scutellarin (50 or 75 mg/kg),
      upregulation of eNOS expression and downregulation of VEGF, bFGF, and iNOS
      expression was observed, whereas scutellarin had no effect on nNOS expression.
      CONCLUSION: Scutellarin has protective effects for cerebral injury through
      regulating the expression of NOS isoforms and angiogenic molecules.

PMID- 16297344
TI  - C16, a novel advanced glycation endproduct breaker, restores cardiovascular
      dysfunction in experimental diabetic rats.
AB  - AIM: Advanced glycation endproducts (AGE) have been implicated in the
      pathogenesis of diabetic complications, including diabetic cardiovascular
      dysfunction. 3-[2-(4-Bromo-phenyl)-1-methyl-2-oxo-ethyl]-4,5,6,7-tetrahydro
      benzothiazol-3-ium bromide (C16), a novel AGE breaker, was investigated for its
      effects on the development of cardiovascular disease in diabetic rats. METHODS:
      Rats that had streptozotocin-induced diabetes for 12 weeks were divided into
      groups receiving C16 or vehicle by gavage. RESULTS: In hemodynamic studies of the
      left ventricle, C16 treatment (25 or 50 mg/kg) for 4 weeks resulted in a
      significant increase in left ventricular systolic pressure, +dp/dt(max), and 
      dp/dt(max) as compared with vehicle-treated diabetic rats. Furthermore, in
      hemodynamic studies of the cardiovascular system, C16 (12.5, 25, or 50 mg/kg)
      treatment for 4 weeks resulted in a dose-dependent and significant increase in
      cardiac output, a reduction of total peripheral resistance, and an increase in
      systemic arterial compliance when compared with vehicle-treated diabetic rats.
      Biochemical studies showed that C16 treatment also resulted in a significant
      decrease in immunoglobulin G-red blood cell surface crosslink content and an
      increase in collagen solubility. Morphological and immunohistochemical
      examinations indicated that C16 was able to prevent increases of the collagen
      type III/I ratio in the aorta and decrease the accumulation of AGE in the aorta.
      CONCLUSION: C16 has the ability to reduce AGE accumulation in tissues in vivo,
      and can restore diabetes-associated cardiovascular disorders in rats. This
      provides a potential therapeutic approach for cardiovascular disease associated
      with diabetes and aging in humans.

PMID- 16297345
TI  - One-oligonucleotide method for constructing vectors for RNA interference.
AB  - AIM: To develop an easy, fast, automated, and inexpensive method for constructing
      short-hairpin-RNA cassettes for RNAi studies. METHODS: Using single
      oligonucleotides, a variety of DNA cassettes for RNAi vectors were constructed in
      only few minutes in an automated manner. The cassettes, targeting the eGFP, were
      cloned into plasmids driven by RNA polymerase III promoter H1. Then, the plasmids
      were transfected into HeLa cells that were later infected with a recombinant
      adenovirus encoding the eGFP gene. The level of eGFP fluorescence was evaluated
      by confocal imaging and flow cytometry. RESULTS: The plasmids constructed with
      the DNA cassettes made by the one-oligonucleotide method inhibited eGFP with
      different potencies, ranging from 55% to 75%. CONCLUSION: By using the method
      reported here, it is possible to simultaneously construct hundreds of different
      DNA cassettes for RNAi experiments in an inexpensive, automated way. This method
      will facilitate functional genomics studies on mammalian cells.

PMID- 16297346
TI  - Enzymological characterization of FII(a), a fibrinolytic enzyme from Agkistrodon
      acutus venom.
AB  - AIM: To study the enzymological characterization of a fibrinolytic enzyme
      (FII(a)) from Agkistrodon acutus venom. METHODS: The fibrinogenolytic effect and
      the influences of several protease inhibitors, chelating agents, and metal ions
      on fibrinogenolytic activity were visualized by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The metal content of FII(a) was determined by
      atomic absorption spectroscopy. RESULTS: After incubation with FII(a) (0.25 g/L),
      Aalpha-, Bbeta- and gamma-chains of fibrinogen disappeared within 5 min, 30 min,
      and 8 h , respectively. The molecular weights of major degradation products were
      45,000 and 41,000, which were different from those bands produced by plasmin. The
      fibrinogenolytic activity of FIIa was strongly inhibited by ethylenediamine
      tetraacetic acid (EDTA), ethyleneglycol tetraacetic acid (EGTA), dithiothreitol
      and cysteine, but not by phenylmethyl-sulfonyl fluoride and soybean trypsin
      inhibitor. Zinc (3171+/-25 mg/kg), potassium (489+/-17 mg/kg) and calcium (319+/
      13 mg/kg) were found in FIIa. Zn2+, Ca2+ and Mg2+ could recover the
      fibrinogenolytic activity of FIIa, which was inhibited by EDTA. Only Ca2+ could
      recover the fibrinogenolytic activity inhibited by EGTA. CONCLUSION: FIIa can
      degrade the Aalpha-, Bbeta- and gamma-chains of fibrinogen. FII(a) is a
      metalloproteinase, and Zn2+, Ca2+, and disulfide bonds are necessary for its
      fibrinogenolytic activity.

PMID- 16297348
TI  - Binding of PLCdelta1PH-GFP to PtdIns(4,5)P2 prevents inhibition of phospholipase
      C-mediated hydrolysis of PtdIns(4,5)P2 by neomycin.
AB  - AIM: To investigate the effects of the pleckstrin homology (PH) domain of
      phospholipase C(delta1) (PLC(delta1)PH) on inhibition of phospholipase C (PLC)
      mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] by
      neomycin. METHODS: A fusion construct of green fluorescent protein (GFP) and PLC
      (delta1)PH (PLC(delta1)PH-GFP), which is known to bind PtdIns(4,5)P2
      specifically, together with laser-scanning confocal microscopy, was used to trace
      PtdIns(4,5)P2 translocation. RESULTS: Stimulation of the type 1 muscarinic
      receptor and the bradykinin 2 receptor induced a reversible PLC(delta1)PH-GFP
      translocation from the membrane to the cytosol in COS-7 cells. PLC inhibitor
      U73122 blocked the translocation. Wortmannin, a known PtdIns kinase inhibitor,
      did not affect the translocation induced by ACh, but blocked recovery after
      translocation, indicating that PtdIns(4,5)P2 hydrolysis occurs through receptor
      mediated PLC activation. Neomycin, a commonly used phospholipase C blocker,
      failed to block the receptor-induced PLCd1PH-GFP translocation, indicating that
      neomycin is unable to block PLC-mediated PtdIns(4,5)P2 hydrolysis. However, in
      the absence of PLCd1PH-GFP expression, neomycin abolished the receptor-induced
      hydrolysis of PtdIns(4,5)P2 by PLC. CONCLUSION: Although PLCd1PH and neomycin
      bind to PtdIns(4,5)P2 in a similar way, they have distinct effects on receptor
      mediated activation of PLC and PtdIns(4,5)P2 hydrolysis.

PMID- 16297347
TI  - Preparation and development of equine hyperimmune globulin F(ab')2 against severe
      acute respiratory syndrome coronavirus.
AB  - AIM: The resurgence of severe acute respiratory syndrome (SARS) is still a threat
      because the causative agent remaining in animal reservoirs is not fully
      understood, and sporadic cases continue to be reported. Developing high titers of
      anti-SARS hyperimmune globulin to provide an alternative pathway for emergent
      future prevention and treatment of SARS. METHODS: SARS coronavirus (CoV)F69
      (AY313906) and Z2-Y3 (AY394989) were isolated and identified from 2 different
      Cantonese onset SARS patients. Immunogen was prepared from SARS-CoV F69 strain.
      Six health horses were immunized 4 times and serum was collected periodically to
      measure the profile of specific IgG and neutralizing antibodies using indirect
      enzyme-linked immunosorbent assay and a microneutralization test. Sera were
      collected in large amounts at the peak, where IgG was precipitated using ammonium
      sulphate and subsequently digested with pepsin. The product was then purified
      using anion-exchange chromatography to obtain F(ab')2 fragments. RESULTS: The
      specific IgG and neutralizing antibody titers peaked at approximately week 7
      after the first immunization, with a maximum value of 1:14210. The sera collected
      at the peak were then purified. Fragment of approximately 15 g F(ab')2 was
      obtained from 1litre antiserum and the purity was above 90% with the titer of
      1:5120, which could neutralize the other strain (SARS-CoV Z2-Y3) as well.
      CONCLUSION: This research provides a viable strategy for the prevention and
      treatment of SARS coronavirus infection with equine hyperimmune globulin, with
      the purpose of combating any resurgence of SARS.

PMID- 16297349
TI  - Inhibitory effect of acetamide-45 on airway inflammation and phosphodiesterase 4
      in allergic rats.
AB  - AIM: To determine the effects of acetamide-45 on respiratory function, airway
      inflammation, and the activity of phosphodiesterase 4 (PDE4) in allergic rats.
      METHODS: Rats were sensitized by a single intramuscular injection with ovalbumin
      (OVA) and were challenged with ovalbumin applied by using an aerosol repeatedly
      for 7 d after 2 weeks. Acetamide-45 at concentrations of 5, 10, or 30 mg/kg was
      then administered by intraperitoneal injection. Changes in dynamic lung
      compliance and lung resistance, the accumulation of inflammatory cells in
      bronchoalveolar lavage, PDE4 activity, and the concentration of interleukin-4 in
      rat lung tissue were determined. RESULTS: Seven days of treatment with acetamide
      45 prevented eosinophil accumulation in allergic rats. At doses of 5, 10, and 30
      mg/kg, acetamide-45 decreased lung resistance to 0.20+/-0.04, 0.25+/-0.07, and
      0.22+/-0.05 cmH2O.s(-1).mL(-1), respectively (P<0.05 vs OVA), and it also
      increased dynamic lung compliance to 0.41+/-0.07, 0.39+/-0.06, and 0.42+/-0.09
      mL/cmH2O (P<0.05 vs OVA). After being treated with different doses of acetamide
      45, the PDE4 activities in lung tissue were 281+/-55, 273+/-57, and 238+/-36
      nmol.g(-1).min( -1) (P<0.05 vs OVA), and the concentrations of interleukin-4 in
      lung tissue were 6.22+/-1.13, 5.95+/-1.20, and 5.68+/-2.20 microg/protein (P<0.05
      vs OVA). CONCLUSIONS: Acetamide-45 was found to improve respiratory function and
      inhibit airway inflammation in this animal model, and the PDE4 activity of lung
      tissue was obviously inhibited. Acetamide-45 was an effective anti-inflammatory
      agent in respiratory inflammation, and the mechanism of its action might depend
      on inhibition of PDE4.

PMID- 16297350
TI  - Effect of cholecystokinin octapeptide on diacylglycerol-PKC signaling pathway in
      rat pulmonary interstitial macrophages stimulated by lipopolysaccharide.
AB  - AIM: To investigate the effect of cholecystokinin octapeptide (CCK-8) on the
      diacylglycerol-protein kinase C (DAG-PKC) signaling pathway in rat pulmonary
      interstitial macrophages (PIM) stimulated by lipopolysaccaride (LPS). METHODS:
      The PIM from rat lung tissues were isolated using the collagenase digestion
      method combined with alveolar lavage and pulmonary vessel perfusion. DAG content
      and PKC activity were measured by radioenzymatic assay. The translocation of
      PKCzeta was determined by semi-quantitative immunoblot analysis. RESULTS: CCK-8,
      at high concentrations (1 x 10(-6) - 1 x 10(-5) mol/L), decreased DAG content and
      inhibited PKC activity and PKCzeta translocation compared with that in rat
      resting PIM of a control group (P< 0.01). LPS increased DAG content, and promoted
      PKC activity and PKCzeta translocation (P< 0.01). CCK-8 decreased LPS-induced DAG
      content and inhibited LPS-induced PKC activity and PKCzeta translocation
      significantly at 1 x 10(-8) - 1 x 10(-5) mol/L (P< 0.01). This inhibitory effect
      of CCK-8 could be abrogated partly by proglumide (non-selective CCK receptor
      antagonist), CR-1409 (selective CCK-A receptor antagonist), and CR-2945
      (selective CCK-B receptor antagonist) in a concentration-dependent manner (P<
      0.01). CONCLUSION: CCK-8 was a negative modulator of the DAG-PKC signaling
      pathway in rat resting PIM, which is very important for maintaining body
      homeostasis. It significantly inhibited LPS-induced DAG content, PKC activity and
      PKCzeta translocation in a concentration-dependent manner. The CCK receptor,
      especially the CCK-A receptor, might play a major role in this process.

PMID- 16297351
TI  - Evaluation of 2 celecoxib derivatives: analgesic effect and selectivity to
      cyclooxygenase-2/1.
AB  - AIM: To evaluate the analgesic effects of 2 celecoxib derivatives and their
      inhibitory effects on cyclooxygenase (COX). METHODS: Four antinociceptive assays
      were used: the acetic acid-induced writhing test, hot plate test, hot tail-flick
      test and formalin test. Three doses were used in the analgesic assays and ED50
      values were calculated. For the selectivity assay, macrophages were incubated
      with test compounds at various concentrations and then stimulated with calcimycin
      or lipopolysaccharide (LPS). The amounts of 6-keto-prostaglandin F1alpha(6-keto
      PGF1alpha) and prostaglandin E2 (PGE2) in the supernatant were examined by
      radioimmunoassay (RIA). The selectivity of the test compounds was expressed as
      the IC(50,COX-1)/IC(50,COX-2) value. RESULTS: Celecoxib and its 2 derivatives had
      a significant analgesic effect. The ED50 values of celecoxib, PC-406 and PC-407
      were 94.2, 67.9, and 63.3 mg/kg, respectively, for the acetic acid-induced
      writhing test; 104.7, 89.1, and 30.0 mg/kg, respectively, for the hot tail-flick
      response test; 60.7, 56.7, and 86.2 mg/kg, respectively, for the hot plate
      response test; 67.1, 55.8, and 68.8 mg/kg, respectively, for the formalin-induced
      response. That is, the ED50 of PC-406 was the lowest for the formalin and hot
      plate tests, which focus on changes above the spinal cord level; however, the
      ED50 of PC-407 was lowest for the tail-flick and writhing tests, which focus on
      changes at the spinal cord level. Celecoxib and PC-407 inhibited COX-1 with IC50
      values of 39.8 and 27.5 nmol/L, respectively. PC-406 inhibited COX-1 with an IC50
      value of more than 1000 nmol/L. The IC50 values for the effect of celecoxib, PC
      406 and PC-407 on COX-2 were 4.8, 8.9, and 1.9 nmol/L respectively. The IC(50,
      COX-1)/IC(50,COX-2) ratios for celecoxib and PC-407 were 8.3 and 14.4, respec
      tively. For PC-406, the ratio was greater than 112.2. CONCLUSION: Derivatives of
      celecoxib via substitution with an isopropyl or naphthyl group at the 5 position
      in the pyrazole ring still have analgesic effects and the ability to selectively
      inhibit COX-2. Substitution with a naphthyl group may have more effect on the
      peripheral pain pathway, whereas substitution with an isopropyl group may have
      more effect on the central pain pathway. This phenomenon occurs partly because
      substitution with an isopropyl group is more beneficial for COX-2 selectivity
      than is substitution with a naphthyl group.

PMID- 16297352
TI  - Body distribution and in situ evading of phagocytic uptake by macrophages of long
      circulating poly (ethylene glycol) cyanoacrylate-co-n-hexadecyl cyanoacrylate
      nanoparticles.
AB  - AIM: To investigate the body distribution in mice of [14C]-labeled poly
      methoxyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate (PEG-PHDCA)
      nanoparticles and in situ evading of phagocytic uptake by mouse peritoneal
      macrophages. METHODS: PEG-PHDCA copolymers were synthesized by condensation of
      methoxypolyethylene glycol cyanoacetate with [14C]-hexadecyl-cyanoacetate. [14C]
      nanoparticles were prepared using the nanoprecipitation/solvent diffusion method,
      while fluorescent nanoparticles were prepared by incorporating rhodamine B. In
      situ phagocytic uptake was evaluated by flow cytometry. Body distribution in mice
      was evaluated by determining radioactivity in tissues using a scintillation
      method. RESULTS: Phagocytic uptake by macrophages can be efficiently evaded by
      fluorescent PEG-PHDCA nanoparticles. After 48 h, 31% of the radioactivity of the
      stealth [14C]-PEG-PHDCA nanoparticles after iv injection was still found in
      blood, whereas non-stealth PHDCA nanoparticles were cleaned up from the
      bloodstream in a short time. The distribution of stealth PEG-PHDCA nanoparticles
      and non-stealth PHDCA nanoparticals in mice was poor in lung, kidney, and brain,
      and a little higher in hearts. Lymphatic accumulation was unusually high for both
      stealth and non-stealth nanoparticles, typical of lymphatic capture. The
      accumulation of stealth PEG-PHDCA nanoparticles in the spleen was 1.7 times as
      much as that of non-stealth PHDCA (P< 0.01). But the accumulation of stealth PEG
      PHDCA nanoparticles in the liver was 0.8 times as much as that of non-stealth
      PHDCA (P< 0.05). CONCLUSION: PEGylation leads to long-circulation of
      nanoparticles in the bloodstream, and splenotropic accumulation opens up the
      potential for further development of spleen-targeted drug delivery.

PMID- 16297353
TI  - Identification of some benproperine metabolites in humans and investigation of
      their antitussive effect.
AB  - AIM: To identify 4 unknown metabolites of benproperine (BPP, 1) in human urine
      after a po dose, and to investigate the antitussive effect of monohydroxylate
      metabolites. METHODS: The putative metabolite references were prepared using
      chemical synthesis. Their structures were identified using 1H and 13C nuclear
      magnetic resonance, and mass spectrometry. The metabolites in human urine were
      separated and assayed using liquid chromatography-ion trap mass spectrometry
      (LC/MS/MS), and further confirmed by comparison of their mass spectra and
      chromatographic retention times with those of synthesized reference substances.
      The antitussive effects of metabolites were evaluated on coughs induced by 7.5%
      citric acid in conscious guinea pigs. RESULTS: 1-[1-Methyl-2-[2
      (phenylmethyl)phenoxy]-ethyl]-4-piperidinol (2), 1-[1-methyl-2-[2
      (phenylmethyl)phenoxy] ethyl]-3-piperidinol (3) and their glucuronides 4 and 5
      were obtained from chemical synthesis. Four urinary metabolites in human urine
      showed peaks with the same chromatographic retention times and mass spectra in
      LC/MS/MS as synthetic substances 2, 3, 4 and 5. Phosphates of compounds 2 and 3
      prolonged the latency of cough and reduced the number of coughs during the 3 min
      test using citric acid, but did not reduce the number of coughs during the 5 min
      immediately after the test in conscious guinea pigs. CONCLUSION: Compounds 2, 3,
      4, and 5 were identified as the metabolites of BPP in human urine. Among them,
      compounds 2 and 3 are inactive in the antitussive effect.

PMID- 16297354
TI  - Stereoselectivity in metabolic 3-reduction of tibolone in healthy Chinese female
      volunteers.
AB  - AIM: To investigate the stereoselectivity in human metabolic 3-reduction of
      tibolone. METHODS: Twenty healthy Chinese female volunteers were given a single
      oral dose of tibolone (2.5 mg), and serial blood samples were collected after
      treatment. The plasma concentrations of the two pharmacologically active 3
      hydroxyl metabolites of tibolone, 3alpha-hydroxyl-7-methyl- norethynodrel (3alpha
      HMN) and 3beta-hydroxyl-7-methyl- norethynodrel (3beta-HMN) in plasma were
      determined by using a validated liquid chromatography-mass spectrometry (LC-MS)
      method. RESULTS: The apparent elimination half-life (T(1/2) of 3alpha-HMN was
      1.43+/-0.52 h, and that of 3beta-HMN was 1.53+/-0.60 h. Maximum plasma
      concentrations (C(max)) were found to be 8.75+/-4.36 microg/L for 3alpha-HMN and
      3.59+/-1.81 microg/L for 3beta-HMN. Areas under the plasma concentration versus
      time curve (AUC(0-t)) were 26.30+/-12.14 microg.h(-1).L(-1) for 3alpha-HMN and
      9.89+/-4.93 microg.h(-1).L(-1) for 3beta-HMN. CONCLUSION: Stereo-selective
      differences exist in the pharmacokinetics of tibolone metabolism in humans.

PMID- 16297355
TI  - Newborn screening for congenital heart defects: a systematic review and cost
      effectiveness analysis.
AB  - OBJECTIVES: To provide evidence to inform policy decisions about the most
      appropriate newborn screening strategy for congenital heart defects, identifying
      priorities for future research that might reduce important uncertainties in the
      evidence base for such decisions. DATA SOURCES: Electronic databases. Groups of
      parents and health professionals. REVIEW METHODS: A systematic review of the
      published medical literature concerning outcomes for children with congenital
      heart defects was carried out. A decision analytic model was developed to assess
      the cost-effectiveness of alternative screening strategies for congenital heart
      defects relevant to the UK. A further study was then carried out using a self
      administered anonymous questionnaire to explore the perspectives of parents and
      health professionals towards the quality of life of children with congenital
      heart defects. The findings from a structured review of the medical literature
      regarding parental experiences were linked with those from a focus group of
      parents of children with congenital heart defects. RESULTS: Current newborn
      screening policy comprises a clinical examination at birth and 6 weeks, with
      specific cardiac investigations for specified high-risk children. Routine data
      are lacking, but under half of affected babies, not previously identified
      antenatally or because of symptoms, are identified by current newborn screening.
      There is evidence that screen-positive infants do not receive timely management.
      Pulse oximetry and echocardiography, in addition to clinical examination, are
      alternative newborn screening strategies but their cost-effectiveness has not
      been adequately evaluated in a UK setting. In a population of 100,000 live-born
      infants, the model predicts 121 infants with life-threatening congenital heart
      defects undiagnosed at screening, of whom 82 (68%) and 83 (69%) are detected by
      pulse oximetry and screening echocardiography, respectively, but only 39 (32%) by
      clinical examination alone. Of these, 71, 71 and 34, respectively, receive a
      timely diagnosis. The model predicts 46 (0.5%) false-positive screening diagnoses
      per 100,000 infants with clinical examination, 1168 (1.3%) with pulse oximetry
      and 4857 (5.4%) with screening echocardiography. The latter includes infants with
      clinically non-significant defects. Total programme costs are predicted of pound
      300,000 for clinical examination, pound 480,000 for pulse oximetry and pound 3.54
      million for screening echocardiography. The additional cost per additional timely
      diagnosis of life-threatening congenital heart defects ranges from pound 4900 for
      pulse oximetry to pound 4.5 million for screening echocardiography. Including
      clinically significant congenital heart defects gives an additional cost per
      additional diagnosis of pound 1500 for pulse oximetry and pound 36,000 for
      screening echocardiography. Key determinants for cost-effectiveness are detection
      rates for pulse oximetry and screening echocardiography. Parents and health
      professionals place similar values on the quality of life outcomes of children
      with congenital heart defects and both are more averse to neurological than to
      cardiac disability. Adverse psychosocial effects for parents are focused around
      poor management and/or false test results. CONCLUSIONS: Early detection through
      newborn screening potentially can improve the outcome of congenital heart
      defects; however the current programme performs poorly, and lacks monitoring of
      quality assurance, performance management and longer term outcomes. Pulse
      oximetry is a promising alternative newborn screening strategy but further
      evaluation is needed to obtain more precise estimates of test performance and to
      inform optimal timing, diagnostic and management strategies. Although screening
      echocardiography is associated with the highest detection rate, it is the most
      costly strategy and has a 5% false-positive rate. Improving antenatal detection
      of congenital heart defects increases the cost per timely postnatal diagnosis
      afforded by any newborn screening strategy but does not alter the relative
      effects of the strategies. An improvement of timely management of screen positive
      infants is essential. Further research is required to refine the detection rate
      and other aspects of pulse oximetry, to evaluate antenatal screening strategies
      more directly, and to investigate the psychosocial effects of newborn screening
      for congenital heart defects.

PMID- 16297356
TI  - Barbara Alving, MD.

PMID- 16297361
TI  - Peroxisome proliferator-activated receptor alpha L162V polymorphism in
      nonalcoholic steatohepatitis and genotype 1 hepatitis C virus-related liver
      steatosis.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor alpha (PPARalpha) plays
      important roles in lipid metabolism. A recently discovered L162V polymorphism of
      the PPARalpha gene is associated with enhanced transcriptional activity. In this
      study, the frequency of L162V was investigated in nonalcoholic steatohepatitis
      (NASH) and genotype 1 hepatitis C virus (HCV)-related liver steatosis. METHODS:
      Seventy-two NASH and 141 HCV-infected patients (54 with steatosis, 87 without
      steatosis) and 119 healthy controls were included. L162V polymorphism of the
      PPARalpha gene was analyzed by polymerase chain reaction (PCR) and restriction
      fragment length polymorphism (RFLP). RESULTS: PCR and RFLP analysis of the
      related gene segment was successful in 93%, 96%, and 100% of NASH and HCV
      infected patients and controls, respectively. The frequency of the L162V
      polymorphism was similar in the NASH and HCV-infected patients and controls
      (5.9%, 3.6%, and 2.5%, respectively). No difference in the frequency of this
      polymorphism was observed in HCV-infected patients with or without significant
      liver steatosis. L162V was not associated with obesity, type 2 diabetes mellitus,
      hypercholesterolemia, or hypertriglyceridemia. CONCLUSIONS: Neither NASH nor
      genotype 1 HCV-related liver steatosis seems to be associated with the PPARalpha
      L162V polymorphism. This polymorphism may have no association with the presence
      of type 2 diabetes mellitus, obesity, or various blood lipid alterations in NASH
      and HCV-infected patients.

PMID- 16297362
TI  - Atrial natriuretic peptides: anticancer agents.
AB  - Atrial natriuretic peptides (ANPs) consist of a family of six peptide hormones
      that are synthesized by three different genes and then stored as three different
      prohormones. Within the 126-amino acid ANP prohormone are four peptide hormones:
      long-acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide, and
      ANP, whose main known biologic properties are blood pressure regulation and
      maintenance of plasma volume. The newest discovered property of these peptide
      hormones is their anticancer effects. Vessel dilator, LANP, kaliuretic peptide,
      and ANP decrease the number of human pancreatic adenocarcinoma cells in culture
      by 65%, 47%, 37%, and 34%, respectively, within 24 hours at their 1 microM
      concentrations. Similar results have been found with breast adenocarcinomas,
      squamous cell lung cancer, and small cell lung cancer cells, each associated with
      an 83% or greater inhibition of deoxyribonucleic acid (DNA) synthesis by these
      four peptide hormones. Brain natriuretic peptide has no effects even when
      increased 100-fold (ie, 100 microM). C-type natriuretic peptide has no effects
      when increased 10-fold, but when increased 100-fold, it decreases 39% of the
      cancer cells. At this higher 100 microM concentration, vessel dilator kills 92%
      of the cancer cells within 24 hours. The four peptide hormones synthesized by the
      ANP gene given subcutaneously via osmotic pumps in athymic mice with human
      pancreatic adenocarcinomas completely stop the growth of these adenocarcinomas at
      1 week. Vessel dilator, LANP, and kaliuretic peptide within 1 week decrease the
      volume by 49%, 28%, and 11% of the human pancreatic adenocarcinomas, which, with
      current anticancer treatment, have a mean survival of only 4 months.

PMID- 16297360
TI  - Inducible nitric oxide synthase inhibitors reduce urinary markers of systemic
      oxidant stress in murine proliferative lupus nephritis.
AB  - BACKGROUND: Proliferative lupus nephritis (PLN) is characterized by increased
      expression of inducible nitric oxide (NO) synthase (iNOS). Inhibition of iNOS
      with NG-monomethyl L-arginine (L-NMMA) abrogates renal disease in two models of
      murine PLN, but the mechanism of this effect is unknown. Reactive oxygen species
      have both direct and indirect pathogenic effects in inflammatory lesions and are
      therefore potentially an important therapeutic target in PLN. We hypothesized
      that inhibition of iNOS activity would reduce ROS production in murine PLN.
      METHODS: A dose escalation of L-NMMA (0, 20, 100, and 500 mg/kg/day) was
      performed in New Zealand Black x New Zealand White F1 (NZB/W) mice with active
      renal disease. Twenty-four-hour urine nitrate + nitrite (NOX) was measured with a
      chemiluminescence NO analyzer. Twenty-four-hour urine 8-isoprostane F2alpha (8
      iso-PGF2alpha) was measured by gas chromatography-negative ion chemical
      ionization mass spectrometry. MRL-MpJFASlpr (MRL/lpr) and NZB/W mice were divided
      into three groups and given either L-NMMA, L-N6-iminoethyl-lysine (L-NIL), or
      distilled water for 2 weeks. Urine NOX and 8-iso-PGF2alpha were determined after
      2 weeks. RESULTS: L-NMMA reduced both urine NOX and 8-iso-PGF2alpha levels in a
      dose-dependent fashion in NZB/W and MRL/lpr mice. Urine NOX and 8-iso-PGF2alpha
      levels were highly correlated. Both specific (L-NIL) and nonspecific (L-NMMA)
      iNOS inhibition reduced urine NOX and 8-iso-PGF2alpha levels in both models of
      murine PLN. CONCLUSION: These findings suggest that iNOS activity is a major
      source of reactive oxidant stress in these models of murine PLN. Future studies
      will address the pathogenic role of reactive oxygen stress in PLN.

PMID- 16297364
TI  - Natriuretic peptides in acute and chronic kidney disease and during renal
      replacement therapy.
AB  - Plasma levels of natriuretic peptides are elevated in patients with chronic
      kidney disease owing to impairment of renal function, hypertension, hypervolemia,
      and/or concomitant heart disease. Proteinuria and/or immunosuppression also
      contribute to enhanced plasma levels and increased urinary excretion of
      natriuretic peptides. Atrial natriuretic peptide (ANP) and particularly brain
      natriuretic peptide (BNP) levels are linked independently to left ventricular
      mass and function and predict total and cardiovascular mortality. ANP and BNP
      decrease significantly during hemodialysis treatment but increase again during
      the interdialytic interval. Intraperitoneal administration of ANP decreases
      peritoneal fluid and glucose absorption, as well as lymphatic flow rate.
      Successful kidney transplant normalizes the plasma levels of natriuretic peptides
      in the majority of patients. In experimental animals but not in humans, ANP
      administration protects against ischemic acute renal failure. Since proANP31-67
      peptide does not cause hypotension, this vessel dilator may protect the kidney
      during acute renal failure by intrarenal vasodilation and stimulation of
      endogenous prostaglandin E2 synthesis.

PMID- 16297365
TI  - Determinants of natriuretic peptide production by the heart: basic and clinical
      implications.
AB  - The cardiac natriuretic peptides (NPs) atrial natriuretic factor (ANF) and brain
      natriuretic peptide (BNP) are polypeptide hormones synthesized, stored, and
      secreted by cardiac muscle cells (cardiocytes). The NPs modulate extracellular
      fluid volume and blood pressure and have potent growth-regulating properties,
      which make them of great interest for cardiac remodeling in acute myocardial
      infarction and congestive heart failure. We have observed that the production of
      NP can be coordinately or discoordinately regulated. In the former type, muscle
      stretch-elicited secretion triggers signals mediated by Gi/o protein, whereas
      agonists such as endothelin 1 independently signal through Gq. Discoordinated
      regulation is observed following stimulations by some cytokines, which
      selectively up-regulate BNP. This regulation takes place at the translational and
      transcriptional levels and is dependent on a p38 signaling pathway. Further
      details of processes regulating NP secretion need to be defined to develop a
      comprehensive view of the endocrine function of the heart. Nevertheless,
      translational research in the area of NPs has demonstrated the usefulness of
      these hormones as a marker of disease and as potential therapeutic agents. The
      latter application of NP is particularly attractive given that ANF and BNP
      possess pharmacologic actions that require polypharmacy in the treatment of acute
      myocardial infarction and congestive heart failure.

PMID- 16297366
TI  - Natriuretic peptides: novel therapeutic targets in heart failure.
AB  - Since the discovery of the cardiac hormone atrial natriuretic peptide by de Bold
      and colleagues in 1981, the field of natriuretic peptides has significantly
      advanced with translation of new knowledge to the clinical practice of heart
      failure. This new knowledge builds on the importance of cardiorenal mechanisms
      that contribute to optimal cardiovascular regulation. Recent investigations by
      our group and others have also established the direct myocardial actions of the
      natriuretic peptides, broadening their therapeutic potential beyond renal
      mechanisms. Indeed, a potential therapeutic target is cardiac remodeling and
      fibrosis based on the unique cardiorenal and humoral protective properties that
      natriuretic peptides possess. We review new insights into the natriuretic peptide
      system and specifically focus on the possible role of natriuretic peptides as a
      new therapeutic strategy to limit cardiac remodeling and fibrosis to delay
      worsening of cardiac function and the progression of heart failure.

PMID- 16297368
TI  - [Management of iatrogenic ureteral lesions].

PMID- 16297369
TI  - p38 MAP kinase regulates benzo(a)pyrene-induced apoptosis through the regulation
      of p53 activation.
AB  - Polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP), are widespread in
      the environment and cause untoward effects, including carcinogenesis, in
      mammalian cells. However, the molecular mechanism of apoptosis by BaP is remained
      to be elusive. Pharmacological inhibition of p38 kinase markedly inhibited the
      BaP-induced cytotoxicity, which was proven as apoptosis characterized by an
      increase in sub-G(0)/G(1) fraction of DNA content, ladder-pattern fragmentation
      of genomic DNA, and catalytic activation of caspase-3 with PARP cleavage. Our
      data also demonstrated that activation of caspase-3 was accompanied with
      activation of caspase-9 and mitochondrial dysfunction, which was also apparently
      suppressed by pretreatment with p38 kinase inhibitors. Also, pharmacological
      inhibition of p38 markedly inhibited the phosphorylation, accumulated expression,
      and transactivation activity of p53 in BaP-treated cells. Adenoviral
      overexpression of human p53 (wild-type) further augmented in increase of PARP
      cleavage and the sub-G(0)/G(1) fraction of DNA content. Furthermore, p53 mediated
      apoptotic activity in BaP-treated cells was inhibited by p38 kinase inhibitor.
      The current data collectively indicate that BaP induces apoptosis of Hepa1c1c7
      cells via activation of p53-related signaling, which was, in part, regulated by
      p38 kinase.

PMID- 16297370
TI  - Nucleoside triphosphate synthesis catalysed by adenylate kinase is ADP dependent.
AB  - Adenylate kinase (Adk) that catalyses the synthesis of ADP from ATP and AMP has
      also been shown to perform an ATP dependent phosphorylation of ribo- and
      deoxynucleoside diphosphates to their corresponding nucleoside triphosphate;
      ATP+(d)NDP<-->ADP+(d)NTP. This reaction, suggested to occur by the transfer of
      the gamma-phosphoryl from ATP to the nucleoside diphosphate, is overall similar
      to that normally carried out by nucleoside diphosphate kinase (Ndk). Accordingly,
      Adk was proposed to be responsible for residual Ndk-like activity measured in a
      mutant strain of Escherichia coli, where the ndk gene was disrupted. We present
      data supporting a mechanism for the synthesis of nucleoside triphosphates by Adk
      that unlike the previously suggested mechanism mentioned above are in complete
      agreement with the current knowledge about the Adk enzyme and its various
      catalytic properties. We propose that nucleoside triphosphate synthesis occurs by
      beta-phosphoryl transfer from ADP to any bound nucleoside diphosphate. Our
      results point to the fact that the proposed Ndk-like mechanism of Adk originated
      from an erroneous interpretation of data, in that contamination of ATP
      preparations with AMP and ADP was not taken into account. Our results also
      address the proposed role of Adk in restoring a normal growth rate of mutant
      strains of E. coli lacking Ndk. These mutant strains apparently, in spite of a
      mutator phenotype, are able to synthesise nucleoside triphosphates by alternative
      pathways to maintain the same growth rate as the wildtype.

PMID- 16297371
TI  - Identification of two distinct intracellular localization signals in STT3-B.
AB  - The STT3 subunit of the oligosaccharyltransferase complex plays a critical role
      in the N-glycosylation process. From Arabidopsis thaliana to Homo sapiens, two
      functional STT3 isoforms have been identified, STT3-A and STT3-B. We report that
      the last transmembrane (TM) segment of STT3-B corresponds to a topogenic
      determinant that is sufficient for proper integration and orientation of STT3-B C
      terminal domain. Notably, the last TM segment of STT3-A and -B isoforms present
      major differences in amino acid sequence and predicted 3D structure. We also
      identified a bipartite nuclear targeting sequence in the C-terminal tail of STT3
      B that is absent in STT3-A. The latter sequence is sufficient to induce nucleolar
      localization of a reporter protein. Our results show that STT3-A and -B display
      two structural differences that may have a drastic influence on their function
      and might account for the remarkable evolutionary conservation of the two STT3
      paralogs.

PMID- 16297372
TI  - Mapping the tropomyosin isoform 5 binding site on human erythrocyte tropomodulin:
      further insights into E-Tmod/TM5 interaction.
AB  - Actin protofilaments in the erythrocyte membrane skeleton are uniformly
      approximately 37nm. This length may be in part attributed to a "molecular ruler"
      made of erythrocyte tropomodulin (E-Tmod) and tropomyosin (TM) isoforms 5 or 5b.
      We previously mapped the E-Tmod binding site to TM5 N-terminal heptad repeat
      residues "a" (I(7), I(14)), "d" (V(10)) and "f" (R(12)). We now map the TM5
      binding site to E-Tmod residues at L(116), E(117) and/or E(118) by identifying
      among 35 deletion clones and a series of point mutations that no longer bind to
      human TM5 and rat TM5b. Upstream residues 71-104 contain an actin binding site.
      The N-terminal "KRK ring" may participate in balancing electrostatic force with
      hydrophobic interaction in dimerization of TM and its binding to E-Tmod.

PMID- 16297373
TI  - Inhibition by calyculin A and okadaic acid of the Ca(2+) release-activated Ca(2+)
      entry pathway in rat basophilic leukemia cells: evidence for regulation by type
      1/2A serine/threonine phosphatase activity.
AB  - Using a combination of fluorescence measurements of intracellular Ca(2+) ion
      concentration ([Ca(2+)](i)) and membrane potential we have investigated the
      sensitivity to serine/threonine phosphatase inhibition of Ca(2+) entry stimulated
      by activation of the Ca(2+) release-activated Ca(2+) (CRAC) entry pathway in rat
      basophilic leukemia cells. In both suspension and adherent cells, addition of the
      type 1/2A phosphatase inhibitor calyculin A, during activation of CRAC uptake,
      resulted in a fall in [Ca(2+)](i) to near preactivation levels. Pre-treatment
      with calyculin A abolished the component of the Ca(2+) rise associated with
      activation of CRAC uptake and inhibited Mn(2+) entry, consistent with a
      requirement of phosphatase activity for activation of the pathway. Depletion of
      intracellular Ca(2+) stores is accompanied by a large depolarisation which is
      absolutely dependent upon Ca(2+) entry via the CRAC uptake pathway. Application
      of calyculin A or okadaic acid, a structurally unrelated phosphatase antagonist
      inhibits this depolarisation. Taken in concert, these data demonstrate a marked
      sensitivity of the CRAC entry pathway to inhibition by calyculin A and okadaic
      acid.

PMID- 16297374
TI  - Differential response of normal, dedifferentiated and transformed thyroid cell
      lines to cisplatin treatment.
AB  - The effects of cisplatin (cisPt) on the extra cellular signal-regulated kinase
      (ERK) and the protein kinase B (PKB/Akt), known to play important roles in
      promoting cell survival and in down regulating apoptosis, were investigated in
      thyroid cell lines. The cytotoxic effect of cisPt was highest in normal PC-Cl3
      cells, intermediate in dedifferentiated PC-E1A and PC-raf cells and lowest in
      fully transformed and tumorigenic PC-E1Araf cells. CisPt provoked ERK
      phosphorylation; such phosphorylation was unaltered by Go6976, a conventional PKC
      inhibitor, whilst blocked by low doses (0.1 microM) or high doses (10 microM) of
      GF109203X, an inhibitor of all PKC isozymes, in PC-Cl3 and in PC-E1Araf cells,
      respectively. In PC-E1Araf, but not in PC-Cl3 cells, the cisPt-provoked ERK
      phosphorylation was also blocked by a myristoylated PKC-zeta pseudo substrate
      peptide (PS-zeta). The cytotoxic effects of cisPt increased when cells were pre
      incubated with the mitogen-activated protein kinase (MEK) inhibitor PD98059.
      CisPt provoked the phosphorylation of PKB/Akt and this effect was blocked by
      LY294002, a PI3K inhibitor. In PC-Cl3 cells pre-incubated with LY294002 the
      effects of cisPt on ERK phosphorylation and cell mortality resulted unaffected;
      conversely, LY294002 reduced the ERK phosphorylation and increased cisPt
      cytotoxity of in PC-E1Araf cells. Furthermore, in PC-E1Araf cells pre-incubated
      with LY294002 and PS-zeta ERK phosphorylation was abolished and cisPt
      cytotoxicity was highest. Altogether results highlight a role for PKCs in the
      upstream regulation of ERK pathway facing the cell response to cisPt treatments.
      Understanding the mechanisms by which cells process cisPt provides important
      insights for designing more efficient platinum-based drugs.

PMID- 16297376
TI  - Phase response characteristics of sinoatrial node cells.
AB  - In this work, the dynamic response of the sinoatrial node (SAN), the natural
      pacemaker of the heart, to short external stimuli is investigated using the Zhang
      et al. model. The model equations are solved twice for the central cell and for
      the peripheral cell. A short current pulse is applied to reset the spontaneous
      rhythmic activity of the single sinoatrial node cell. Depending on the stimulus
      timing either a delay or an advance in the occurrence of next action potential is
      produced. This resetting behavior is quantified in terms of phase transition
      curves (PTCs) for short electrical current pulses of varying amplitude which span
      the whole period. For low stimulus amplitudes the transition from advance to
      delay is smooth, while at higher amplitudes abrupt changes and discontinuities
      are observed in PTCs. Such discontinuities reveal critical stimuli, the
      application of which can result in annihilation of activity in central SAN cells.
      The detailed analysis of the ionic mechanisms involved in its resetting behavior
      of sinoatrial node cell models provides new insight into the dynamics and
      physiology of excitation of the sinoatrial node of the heart.

PMID- 16297375
TI  - Evaluation of a new enzymatic method for homocysteine measurement.
AB  - BACKGROUND AND OBJECTIVES: The increased need in clinical chemistry laboratories
      for methods of homocysteine determination, in correlation with cardiovascular
      diseases and nutritional deficient status, has led to the development of
      different analytical methods; fluorescent immunoenzymatic assays and, recently,
      new fully automated spectrophotometric methods are commercially available. In
      this paper, we compared data obtained from a new enzymatic method for
      homocysteine assay (Carolina Liquid Chemistries), with data obtained from a HPLC
      reference method and an immunoenzymatic method (Abbott AxSYM immunoassay).
      RESULTS: The enzymatic method shows a good correlation with both the HPLC (Y = 
      1.3 + 1.02X; R2 = 0.93) and the immunoenzymatic method (Y = 0.7 + 1.02X; R2 =
      0.92), although a bias enhancement was present in some samples. However, the
      enzymatic method shows a superior analytical feasibility because it needs only
      common laboratory instruments (UV-visible spectrophotometer) and can be easily
      adapted to large automatic clinical chemistry analyzers. Moreover, it lowers the
      laboratory cost of the analysis in comparison to both HPLC and immunoenzymatic
      methods. CONCLUSIONS: The enzymatic Carolina Liquid Chemistries method for
      homocysteine assay shows acceptable analytical performance and undoubtedly
      possesses technical and cost advantages.

PMID- 16297377
TI  - Cryopreservation of human teeth for future organization of a tooth bank--a
      preliminary study.
AB  - This study was aimed at evaluating whether cryopreserved teeth can be used for
      future transplantation by examining the viability and differentiation capability
      of periodontal ligament (PDL) cells and measuring the hardness of dental hard
      tissue. Fifty-four teeth were divided into two groups, control and frozen teeth.
      A MTT assay and a TUNEL assay were performed for the examination of the viability
      and apoptotic death of PDL cells. Immunohistochemical staining for alkaline
      phosphatase was performed to observe whether the differentiation capability of
      PDL cells was maintained by the freezing and thawing procedure. Hardness was
      measured to detect whether dental hard tissue was affected by the freezing
      conditions. The MTT and TUNEL assays showed no significant difference in the
      viability of PDL cells between the two groups. The differentiation capability of
      PDL cells was maintained in frozen teeth as evidenced by alkaline phosphatase
      staining. The hardness of frozen teeth was not changed, but a longitudinal
      fracture was found in 25% of the frozen group. The viability and differentiation
      capability of PDL cells were maintained in a frozen environment; however, it is
      thought that a new cryopreservation method preventing fracture of dental hard
      tissue should be developed for clinical application.

PMID- 16297378
TI  - Cryopreservation and biophysical properties of articular cartilage chondrocytes.
AB  - In order to successfully cryopreserve articular cartilage chondrocytes, it is
      important to characterize their osmotic response during the cryopreservation
      process, as the ice forms and the solutes concentrate. In this study,
      experimental work was undertaken to determine the osmotic parameters of articular
      cartilage chondrocytes. The osmotically inactive volume of articular cartilage
      chondrocytes was determined to be 44% of the isotonic volume. The membrane
      hydraulic conductivity parameters for water were determined by fitting a
      theoretical water transport model to the experimentally obtained volumetric
      shrinkage data; the membrane hydraulic conductivity parameter L(Pg) was found to
      be 0.0633 microm/min/atm, and the activation energy E, 8.23 kcal/mol. The
      simulated cooling process, using the osmotic parameters obtained in this study,
      suggests a cooling rate of 80 degrees C/min for the cryopreservation of the
      articular cartilage chondrocytes of hogs. The data obtained in this study could
      serve as a starting point for those interested in cryopreservation of
      chondrocytes from articular cartilage in other species in which there is clinical
      interest and there are no parameters for prediction of responses.

PMID- 16297379
TI  - Endodermal expression of Nkx6 genes depends differentially on Pdx1.
AB  - Nkx family members are essential for normal development of many different tissues
      such as the heart, lungs, thyroid, prostate, and CNS. Here, we describe the
      endodermal expression pattern of three Nkx6 family genes of which two shows
      conserved expression in the early pancreatic epithelium. In chicken, Nkx6.1
      expression is not restricted to the presumptive pancreatic area but is more
      broadly expressed in the endoderm. In mice, expression of Nkx6.1 is restricted to
      the pancreatic epithelium. In both mice and chicken, Nkx6.2 and Pdx1 are
      expressed in very similar domains, identifying Nkx6.2 as a novel marker of
      pancreas endoderm. Additionally, our results show that Nkx6.3 is expressed
      transiently in pancreatic endoderm in chicken but not mouse embryos. At later
      stages, Nkx6.3 is found in the caudal stomach and rostral duodenum in both
      species. Finally, we demonstrate that Pdx1 is required for Nkx6.1 but not Nkx6.2
      expression in mice and that ectopic Pdx1 can induce Nkx6.1 but not Nkx6.2 or
      Nkx6.3 expression in anterior chicken endoderm. These results demonstrate that
      Nkx6.1 lies downstream of Pdx1 in a genetic pathway and that Pdx1 is required and
      sufficient for Nkx6.1 expression in the early foregut endoderm.

PMID- 16297380
TI  - Involvement of spinal GABA receptors in the regulation of intraspinal
      acetylcholine release.
AB  - It has been shown that analgesics such as morphine, lidocaine and clonidine
      increase the release of spinal acetylcholine. Acetylcholine may therefore play an
      important role in the regulation of spinal pain threshold. Since behavioral as
      well as in vitro studies have shown a clear involvement of GABA (gamma-amino
      butyric acid) receptors in the regulation of spinal nociceptive mechanisms, the
      present study focused on the role of GABA receptors for spinal acetylcholine
      release control. GABA receptor agonists and antagonists were infused via a spinal
      microdialysis probe and acetylcholine release was measured. The GABA(A) receptor
      agonist muscimol decreased acetylcholine release and the antagonist bicuculline
      increased acetylcholine release. The GABA(B) receptor agonist baclofen decreased
      acetylcholine release whereas the antagonist saclofen did not change
      acetylcholine release. The results suggest that both GABA receptor subtypes have
      an inhibitory role on spinal dorsal horn acetylcholine release and that the
      GABA(A) receptors are tonically regulating acetylcholine release.

PMID- 16297382
TI  - Melatonin modulates rat myotube-acetylcholine receptors by inhibiting calmodulin.
AB  - Melatonin, the pineal gland hormone, modulates alpha-bungarotoxin sensitive
      nicotinic acetylcholine receptors in sympathetic nerve terminals, cerebellum and
      chick retina imposing a diurnal variation in functional responses [Markus, R.P.,
      Zago, W.M., Carneiro, R.C., 1996. Melatonin modulation of presynaptic nicotinic
      acetylcholine receptors in the rat vas deferens. J. Pharmacol. Exp. Ther. 279, 18
      22; Markus, R.P., Santos, J.M., Zago, W., Reno, L.A., 2003. Melatonin nocturnal
      surge modulates nicotinic receptors and nicotine-induced [3HI] glutamate release
      in rat cerebellum slices. J. Pharmacol. Exp. Ther. 305, 525-530; Sampaio, L.F.S.,
      Hamassaki-Britto, D.E., Markus, R.P., 2005. Influence of melatonin on the
      development of functional nicotinic acetylcholine receptors in cultured chick
      retinal cells. Braz. J. Med. Biol. Res. 38, 603-613]. Here we show that in rat
      myotubes forskolin and melatonin reduced the number of nicotinic acetylcholine
      receptors expressed in plasma membrane. In addition, these cells expressed
      melatonin MT1 receptors, which are known to be coupled to G(i)-protein. However,
      the pharmacological profile of melatonin analogs regarding the reduction in
      cyclic AMP accumulation and number of nicotinic acetylcholine receptors did not
      point to a mechanism mediated by activation of G(i)-protein coupled receptors. On
      the other hand, calmidazolium, a classical inhibitor of calmodulin, reduced in a
      similar manner both effects. Considering that one isoform of adenylyl cyclase
      present in rat myotubes is regulated by Ca2+/calmodulin, we propose that
      melatonin modulates the number of nicotinic acetylcholine receptors via reduction
      in cyclic AMP accumulation.

PMID- 16297381
TI  - Astrapterocarpan isolated from Astragalus membranaceus inhibits proliferation of
      vascular smooth muscle cells.
AB  - The inhibitory effects of astrapterocarpan, formononetin, and calycosin isolated
      from Astragalus membraneceus on platelet-derived growth factor (PDGF)-BB-induced
      proliferative response in rat vascular smooth muscle cells (A10 cells) were
      investigated. Astrapterocarpan significantly inhibited PDGF-BB-induced cell
      proliferation and DNA synthesis in a concentration-dependent manner. This
      inhibition was not attributed to toxicity. In contrast, formononetin and
      calycosin had no effect. We next examined the effect of astrapterocarpan on PDGF
      BB signal transduction. Astrapterocarpan inhibited PDGF-BB-induced
      phosphorylation of extracellular signal-regulated kinase 1/2 (ERIC1/2) mitogen
      activated protein (MAP) kinase. However, this compound had no effect on
      phosphorylation of PDGF-beta-receptor, Akt kinase and p38 MAP kinase. These
      results indicated that astrapterocarpan inhibits PDGF-BB-induced vascular smooth
      muscle cell proliferation and that this effect may be mediated, at least in part,
      by inhibition of the ERK1/2 MAP kinase cascade.

PMID- 16297383
TI  - Does insulin release kinins in rats?
AB  - Rat uterus maintained in situ was used as a bioassay of kinins possibly released
      in vivo by hyperglycaemia or insulin. Intravenous injections of bradykinin
      induced contractions of rat uterus which were suppressed by HOE 140, a bradykinin
      B2 receptor antagonist. Des-Arg9-bradykinin, a kinin B1 receptor agonist, did not
      elicit any response. After propranolol, the effects of bradykinin were enhanced
      and dose-dependent. This potentiation did not appear in adrenalectomized rats.
      Captopril, an angiotensin-converting enzyme (ACE) inhibitor, largely increased
      the effects of bradykinin. In animals pretreated with propranolol, captopril and
      atosiban, an oxytocin antagonist, intravenous infusion of glucose induced
      hyperglycaemia and after a delay increased the uterine contractile activity. This
      contractile effect of glucose was abolished by HOE 140. Infusion of insulin with
      glucose induced contractions of the uterus. These responses did not appear or
      were suppressed by HOE 140 or by soya bean trypsin inhibitor (SBTI), a plasma
      kallikrein inhibitor. These results are direct evidence that insulin induces a
      release of kinins.

PMID- 16297384
TI  - Rat limbal epithelial side population cells exhibit a distinct expression of stem
      cell markers that are lacking in side population cells from the central cornea.
AB  - The side population (SP) phenotype is shared by stem cells in various tissues and
      species. Here we demonstrate SP cells with Hoechst dye efflux were surprisingly
      collected from the epithelia of both the rat limbus and central cornea, unlike in
      human and rabbit eyes. Our results show that rat limbal SP cells have a
      significantly higher expression of the stem cell markers ABCG2, nestin, and notch
      1, compared to central corneal SP cells. Immunohistochemistry also revealed that
      ABCG2 and the epithelial stem/progenitor cell marker p63 were expressed only in
      basal limbal epithelial cells. These results demonstrate that ABCG2 expression is
      closely linked to the stem cell phenotype of SP cells.

PMID- 16297385
TI  - Characterization of centrosomal association of nucleophosmin/B23 linked to Crm1
      activity.
AB  - Nucleophosmin (NPM)/B23 is a multifunctional protein, involving in a wide variety
      of basic cellular processes, including ribosome assembly, DNA duplication,
      nucleocytoplasmic trafficking, and centrosome duplication. It has previously been
      shown that NPM/B23 localizes to centrosomes, and dissociate from centrosomes upon
      phosphorylation by Cdk2/cyclin E. However, detail characterization of centrosomal
      association of NPM/B23 has been hampered by the lack of appropriate antibodies
      that efficiently detects centrosomally localized NPM/B23, as well as by apparent
      loss of natural behavior of NPM/B23 when tagged with fluorescent proteins. Here,
      by the use of newly generated anti-NPM/B23 antibody, we conducted a careful
      analysis of centrosomal localization of NPM/B23. We found that NPM/B23 localizes
      between the paired centrioles of unduplicated centrosomes, suggesting the role of
      NPM/B23 in the centriole pairing. Upon initiation of centrosome duplication, some
      NPM/B23 proteins remain at mother centrioles of the parental centriole pairs. We
      further found that inhibition of Crm1 nuclear export receptor results in both
      accumulation of cyclin E at centrosomes and efficient dissociation of NPM/B23
      from centrosomes.

PMID- 16297387
TI  - Catalytic properties of the bifunctional soybean beta-glucan-binding protein, a
      member of family 81 glycoside hydrolases.
AB  - The beta-glucan-binding protein (GBP) of soybean (Glycine max L.) has been shown
      to contain two different activities. As part of the plasma membrane-localized
      pathogen receptor complex, it binds a microbial cell wall elicitor, triggering
      the activation of defence responses. Additionally, the GBP is able to hydrolyze
      beta-1,3-glucans, as present in the cell walls of potential pathogens. The
      substrate specificity, the mode of action, and the stereochemistry of the
      catalysis have been elucidated. This defines for the first time the inverting
      mode of the catalytic mechanism of glycoside hydrolases belonging to family 81.

PMID- 16297388
TI  - Yeast oligosaccharyltransferase consists of two functionally distinct sub
      complexes, specified by either the Ost3p or Ost6p subunit.
AB  - The key step of N-glycosylation of proteins in the endoplasmic reticulum is
      catalyzed by the hetero-oligomeric protein complex oligosaccharyltransferase
      (OST). It transfers the lipid-linked core-oligosaccharide to selected Asn-X
      Ser/Thr-sequences of nascent polypeptide chains. Biochemical and genetic
      approaches have revealed that OST from Saccharomyces cerevisiae consists of nine
      subunits: Wbp1p, Swp1p, Stt3p, Ost1p, Ost2p, Ost4p, Ost5p, Ostp3 and Ost6p. By
      blue native polyacrylamide electrophoresis we show that yeast OST consists of two
      isoforms with distinct functions differing only in the presence of the two
      related Ost3 and Ost6p proteins. The OST6-complex was found to be important for
      cell wall integrity and temperature stress. Ost3p and Ost6p are not essential for
      OST activity, and can in part displace each other in the complex when
      overexpressed, suggesting a dynamic regulation of the complex formation.

PMID- 16297389
TI  - A new method for the determination of arylesterase activity in human serum using
      simulated body fluid.
AB  - Arylesterase activity (EC 3.1.1.2), one of the three functions of the paraoxonase
      enzyme (PON1), is thought to protect low-density lipoproteins (LDL) and high
      density lipoprotein (HDL) from oxidation and to facilitate reverse cholesterol
      transport. The Eckerson et al. method, which employs Tris/HCl buffer, has been
      extensively used and could be considered as the reference method, although it
      shows relatively low precision and reproducibility. Using simulated body fluid
      (SBF), which simulates blood electrolyte composition, a significant improvement
      in arylesterase activity determination was achieved. Modifications of SBF
      bicarbonate and chloride concentrations did not result in further improvements.
      To validate this method arylesterase activity was measured using SBF and Tris/HCl
      in 23 subjects with increased cardiovascular disease risk. Precision was
      significantly higher using SBF than with Tris/HCl. Data from both methods do not
      significantly differ in samples with arylesterase activity > or = 30.6 U/L using
      SBF, but do differ significantly when very low activity samples (< 30.6 U/L) were
      included. Differences suggest that the Tris/HCl buffer gives misleading activity
      results, especially in very low activity samples. For the first time, results
      suggest that SBF can successfully be used instead of Tris/HCl in arylesterase
      activity determination.

PMID- 16297386
TI  - Endotoxin recognition: in fish or not in fish?
AB  - The interaction between pathogens and their multicellular hosts is initiated by
      activation of pathogen recognition receptors (PRRs). These receptors, that
      include most notably members of the toll-like receptor (TLR) family, recognize
      specific pathogen-associated molecular patterns (PAMPs). TLR4 is a central part
      of the receptor complex that is involved in the activation of the immune system
      by lipopolysaccharide (LPS) through the specific recognition of its endotoxic
      moiety (Lipid A). This is a critical event that is essential for the immune
      response to Gram-negative bacteria as well as the etiology of endotoxic shock.
      Interestingly, compared to mammals, fish are resistant to endotoxic shock. This
      in vivo resistance concurs with in vitro studies demonstrating significantly
      lowered sensitivity of fish leukocytes to LPS activation. Further, our in vitro
      analyses demonstrate that in trout mononuclear phagocytes, LPS fails to induce
      antiviral genes, an event that occurs downstream of TLR4 and is required for the
      development of endotoxic shock. Finally, an in silico approach that includes
      mining of different piscine genomic and EST databases, reveals the presence in
      fish of all of the major TLR signaling elements except for the molecules
      specifically involved in TLR4-mediated endotoxin recognition and signaling in
      mammals. Collectively, our analysis questions the existence of TLR4-mediated
      cellular responses to LPS in fish. We further speculate that other receptors, in
      particular beta-2 integrins, may play a primary role in the activation of piscine
      leukocytes by LPS.

PMID- 16297390
TI  - Impact of HIV and highly active antiretroviral therapy on leukocyte adhesion
      molecules, arterial inflammation, dyslipidemia, and atherosclerosis.
AB  - Highly active antiretroviral therapy (HAART) has greatly extended the lives of
      people infected with the human immunodeficiency virus (HIV). This reduced risk of
      early death from opportunistic infections or other sequelae of HIV infection,
      however, means that other possible causes of death emerge. Myocardial infarction
      has become a matter of particular concern. Two of the main sources of
      cardiovascular disease in this population are believed to be vascular
      inflammation and dyslipidemia. We review the evidence for this hypothesis and
      discuss the relationship of HIV to vascular inflammation. Current treatment
      guidelines do not recommend the immediate initiation of HAART unless warranted,
      potentially allowing long-term, unchecked viral impact on the development of
      atherosclerosis. Finally, we consider the protease inhibitors traditionally
      included in HAART regimens and their relationship to the development of
      dyslipidemia, as well as other classes of antiretrovirals, such as the non
      nucleoside reverse transcriptase inhibitors, which might be a better choice for
      patients with cardiovascular risks. Other strategies, such as pharmacologic,
      nutritional, and physical activity interventions are discussed. The patients who
      might benefit most are those in whom the precursors of vascular plaques, such as
      fatty streak, smooth muscle cell, macrophage, and T-lymphocyte aggregation not
      yet identified by echocardiographic and biopsy findings have already developed as
      a result of unchecked viral inflammation and replication.

PMID- 16297391
TI  - Cytomegalovirus in coronary heart disease.

PMID- 16297392
TI  - Inverse correlation between coronary blood flow velocity and sICAM-1 level
      observed in ischemic heart disease patients.
AB  - Systemic factors and blood flow velocity related to atherosclerosis have been
      examined mainly separately or by in vitro studies. The aim of our study was to
      investigate the association between local coronary blood flow (corrected TIMI
      frame count, CTFC) and systemic atherosclerosis-related inflammatory parameters
      such as soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (Il
      6), high sensitivity C-reactive protein (hsCRP) and von Willebrand factor (vWF)
      in humans. We enrolled the following groups of ischemic heart disease (IHD)
      patients: patients with coronary stenosis and stable (CAD, n = 96) or unstable
      angina (ACS, n = 27), patients with documented myocardial ischemia and normal
      coronary angiogram (NEG, n = 68). Patient groups showed only marginal differences
      in CTFC or sICAM-1 levels. In contrast, when IHD patients were studied
      individually, general positive correlation was found between CTFC and sICAM-1
      level (r = 0.33; in NEG r = 0.25; in CAD r = 0.37; in ACS r = 0.61), being the
      strongest in ACS. The relation was independent from age, gender, BMI, smoking,
      hypertension, diabetes, previous myocardial infarction, family history of IHD,
      medication, hsCRP, IL-6 and vWF levels. (odds ratio, OR = 6.4; CI 95%: 2.43
      16.84; p < 0.05). Nevertheless, correlation between CTFC and IL-6, hsCRP, vWF
      levels was not found. These results indicate inverse correlation between coronary
      blood flow and adhesion molecule production independently from conventional
      cardiovascular risk factors and inflammatory markers.

PMID- 16297393
TI  - Development of a quantitative method for determination of acrylamide in infant
      powdered milk and baby foods in jars using isotope dilution liquid
      chromatography/electrospray ionization tandem mass spectrometry.
AB  - An improved method has been developed for the determination of acrylamide in
      infant powdered milk and baby foods in jars, a particular class of foodstuffs
      which represent an important source of nutrition for young infants and babies.
      This method uses isotope dilution liquid chromatography coupled to a tandem mass
      spectrometer with electrospray ionization and is significantly more sensitive
      than previous published methods with a limit of quantification estimated at 1
      microg kg(-1). The new method offers effective sample preparation procedures
      including defatting with petroleum ether, extraction with aqueous solution of
      sodium chloride, further liquid-liquid extraction with ethyl acetate and clean-up
      by solid-phase extraction (SPE) with HLB 200 mg cartridges. The analytical method
      was well validated and good results were obtained with respect to repeatability
      (RSD < 5%) and recovery (86-97%) which fulfilled the requirements defined by
      European Union (EU) legislation. The acrylamide level in infant powdered milk and
      baby foods in jars were 3.01-9.06 microg kg(-1) and 6.80-124.93 microg kg(-1),
      respectively. Especially, this new method is successfully applied to the trace
      quantification of acrylamide in infant/baby foods, the content of which is less
      than 10 microg kg(-1).

PMID- 16297394
TI  - Rapid and ultrasensitive determination of ephedrine and pseudoephedrine
      derivatizated with 5-(4,6-dichloro-s-triazin-2-ylamino) fluorescein by micellar
      electrokinetic chromatography with laser-induced fluorescence detection.
AB  - This paper presents a micellar electrokinetic chromatography method with laser
      induced fluorescence detection to analyze ephedrine (E) and pseudoephedrine (PE)
      after derivatizated with 5-(4,6-dichloro-s-triazin-2-ylamino) fluorescein. The
      optimum derivatization conditions were: 0.05 M Na2CO(3/NaHCO3 (pH 9.5), reaction
      time 30 min at 45 degrees C, molar ratio of DTAF to E and PE mixture 20:1. The
      baseline separation was achieved within 8 min with running buffer composed of 20
      mM borate+20 mM SDS+15% acetonitrile (v/v) (adjusted pH 9.8), and applied voltage
      of 20 kV. Good linearity relationships (correlation coefficients: 0.9906 for E
      and 0.9941 for PE) between the peak heights and concentration of the analytes
      were obtained (2.5-50 ngmL(-1)). The detection limits for E and PE were 3.85 x
      10(-4) and 1.41 x 10(-4)ngmL(-1), respectively, which indicated that the proposed
      method surpassed other chromatographic alternatives in terms of limit of
      detection by at least 10(3) folds. The method was applied to the analysis of the
      two alkaloids in ephedra herb plants and its preparations with recoveries in the
      range of 89.6-107.0%.

PMID- 16297395
TI  - Determination of ammonium in river water and sewage samples by capillary zone
      electrophoresis with direct UV detection.
AB  - We developed capillary zone electrophoresis (CZE) with direct UV detection for
      determination of ammonium in environmental water samples. Ammonium in the samples
      was partly converted into ammonia in the alkaline background electrolyte (BGE)
      during migration and was detected by molecular absorption of ammonia at 190 nm in
      approximately 7 min. The limit of detection (LOD) for ammonium was 0.24 mg/l (as
      nitrogen) at a signal-to-noise ratio of three. The respective values of the
      relative standard deviation (RSD) of peak area, peak height, and migration time
      for ammonium were 2.1, 1.8, and 0.46%. Major alkali and alkaline earth metal ions
      coexisting in the samples did not interfere with ammonium determination by the
      proposed method. The proposed method determined ammonium in surface water and
      sewage samples. The results were compared to those obtained using ion
      chromatography (IC).

PMID- 16297396
TI  - Chemical variance, a useful tool for the interpretation and analysis of two
      dimensional chromatograms.
AB  - A new method is presented for the analysis of comprehensive two-dimensional data.
      The approach complements existing chemometric methods for analysing these kinds
      of data (e.g. multivariate-curve-resolution methods, MCR), and is especially
      suited for the analysis of families of compounds. The method is based on finding
      a new pair of axes (replacing the retention time axes) to represent the data. A
      drop in the matrix rank is observed when one of the axes collects all the
      variance for a certain family of compounds. This is achieved by introducing
      retention models (in both chromatographic dimensions) that describe the behaviour
      of a family of compounds as a function of the property that varies between the
      members. After this transformation, a single family of compounds gives rise to a
      single source of variance. This suggests the application of MCR techniques in a
      second step to separate the contributions of different (overlapped) families of
      compounds. For the latter application, more research has to be performed. The
      approach is illustrated using the separation of families of functional
      poly(methyl-methacrylate) polymers with different numbers of hydroxyl end groups
      and degrees of polymerisation or, equivalently, with the molecular weight as the
      key descriptive property within one family.

PMID- 16297397
TI  - Bubble vortex at surfaces of evaporating liquids.
AB  - Air bubble in volatile liquid on exiting to the surface spins a vortex
      maintaining integrity of the film over an indefinite period of time. The shear
      stress associated with the surface tension increase in the adiabatic evaporation
      cooling drags the warmer liquid inwards into the film counteracting its capillary
      drainage out under gravity. The chaotic patterns, visualized with the aid of
      light interferometry, depend on liquid volatility, degree of vapor saturation,
      and air convection. The circulation intensifies and the frequency of hydrodynamic
      instabilities in the multiphase flow increases on the transition to strong
      turbulent regimes with increasing evaporation rate. Self-consistency of the
      physical mechanisms of solute and evaporation inhibition of bubble coalescence is
      verified through dimensional parametric analysis.

PMID- 16297398
TI  - The geometry of primary drainage.
AB  - We show that arc menisci configuration under primary drainage in capillary tube
      cross sections and, by extension, in throats in the void structure of rock and
      soil, can be understood in terms of the computational geometry theory of medial
      axis analysis. The solution for arc meniscus configuration is developed for cross
      sections of arbitrary, simply connected polygonal shape at both entry- and over
      pressure values during primary drainage for arbitrary values of wetting angle.
      Using this solution technique, we have obtained highly accurate solutions of
      entry pressure arc meniscus radius for over 21,500 throats obtained from analysis
      of computed tomography images in a suite of 4 Fontainebleau core samples ranging
      from 7.5 to 22% porosity. We show that the ratio A/P, of throat area to throat
      perimeter, is an excellent predictor of entry pressure meniscus radius (and hence
      entry pressure) for primary drainage for real pores, while inscribed radius and
      area equivalent radius over-predict entry pressure meniscus radius by factors of
      1.5-3, and are consequently poor predictors.

PMID- 16297399
TI  - Synthesis of silica hollow spheres assisted by ultrasound.
AB  - A simple and effective method for synthesizing silica hollow spheres is
      presented. The synthesis utilizes vesicles from oppositely charged surfactants
      sodium dodecyl sulfate (SDS) and tetrapropylammonium bromide (TPAB) aqueous
      solution as template for the silica growth. Tetraethyl orthosilicate (TEOS) is
      added to the vesicular template as a precursor for the silica formation.
      Ultrasound was employed to accelerate the formation of vesicles template. The
      morphology of the silica spheres is uniform and well-defined (diameter: 200 nm-5
      microm, wall thickness: 50 nm). The product was also characterized by FTIR, TG
      DTA, N2 adsorption. TEM images reveal that the spheres have structure stability
      after calcinations at 550 degrees C.

PMID- 16297400
TI  - The effects of energy sites on adsorption of Lennard-Jones fluids and phase
      transition in carbon slit pore of finite length a computer simulation study.
AB  - A Monte Carlo simulation method is used to study the effects of adsorption
      strength and topology of sites on adsorption of simple Lennard-Jones fluids in a
      carbon slit pore of finite length. Argon is used as a model adsorbate, while the
      adsorbent is modeled as a finite carbon slit pore whose two walls composed of
      three graphene layers with carbon atoms arranged in a hexagonal pattern.
      Impurities having well depth of interaction greater than that of carbon atom are
      assumed to be grafted onto the surface. Different topologies of the impurities;
      corner, centre, shell and random topologies are studied. Adsorption isotherms of
      argon at 87.3 K are obtained for pore having widths of 1, 1.5 and 3 nm using a
      Grand Canonical Monte Carlo simulation (GCMC). These results are compared with
      isotherms obtained for infinite pores. It is shown that the surface heterogeneity
      affects significantly the overall adsorption isotherm, particularly the phase
      transition. Basically it shifts the onset of adsorption to lower pressure and the
      adsorption isotherms for these four impurity models are generally greater than
      that for finite pore. The positions of impurities on solid surface also affect
      the shape of the adsorption isotherm and the phase transition. We have found that
      the impurities allocated at the centre of pore walls provide the greatest
      isotherm at low pressures. However when the pressure increases the impurities
      allocated along the edges of the graphene layers show the most significant effect
      on the adsorption isotherm. We have investigated the effect of surface
      heterogeneity on adsorption hysteresis loops of three models of impurity
      topology, it shows that the adsorption branches of these isotherms are different,
      while the desorption branches are quite close to each other. This suggests that
      the desorption branch is either the thermodynamic equilibrium branch or closer to
      it than the adsorption branch.

PMID- 16297401
TI  - Growth mechanism of soap-free polymerization of styrene investigated by AFM.
AB  - To clarify the growth mechanism of polystyrene (PSL) particles in the soap-free
      polymerization, characteristics of not only particles but also polymeric
      materials floating in the bulk were investigated on the molecular scale by using
      atomic force microscope (AFM), where a cationic initiator V-50 is used to make
      the formed polymeric materials transfer on the mica plate in sampling. Our main
      attention here is to know the reason why the particle size increases with
      increasing initiator concentration in the production of PSL particles. The
      following are found. (1) As far as the initiators and monomers remain in the bulk
      solution, the polymeric materials are born in the bulk continuously, because of
      the slow decomposition rate of initiators. (2) The growth of particles at the
      early stage of t(r) > or = 0.75 h is considered to be attributable mainly to the
      particle swelling by absorbing monomers from the bulk. The rapid growth at the
      intermediate stage is due to the deposition of polymeric materials in the bulk on
      the particle surface and their simultaneous swelling by monomers in the bulk. (3)
      The reason why the particle size increases with increasing concentration of
      initiator is that the growth process is controlled by the deposition rate of
      polymeric materials in the bulk whose amount increases with the initiator
      concentration. (4) The particle size and the smoothness of particle surface
      depend on the relative concentration of initiators and monomers remained.

PMID- 16297402
TI  - Safety conscious planning in small and medium-sized MPOs and rural planning
      agencies: results of a domestic scan.

PMID- 16297403
TI  - Applying user feedback to improve data access and usability: Massachusetts beta
      test results.

PMID- 16297404
TI  - A new model for outcome prediction in intra-abdominal sepsis by the linear
      discriminant function analysis of IL-6 and IL-10 at different heart rates.
AB  - BACKGROUND: The inflammatory response plays an important role in the pathogenesis
      of sepsis, and the prognosis is known to be affected by the pro-inflammatory and
      anti-inflammatory cytokines. Therefore, a simple and reliable outcome prediction
      function that derived from IL-6 and IL-10 was hypothesized. MATERIAL AND METHODS:
      We used 27 Sprague-Dawley rats, weighing 250 to 300 g, underwent cecal ligation
      and puncture (CLP) procedures and femoral arterial catheterization. When the
      heart rates reached 1.15, 1.25, and 1.35 times that of the baseline heart rate,
      blood sampling was done for IL-6 and IL-10. The prognosis was followed up for 3
      days after CLP, and all rats were then divided into survival or non-survival
      groups. Finally, the relationships among survival condition, heart rate, IL-6,
      and IL-10 were analyzed by two-way ANOVA and multiple comparison. A linear
      discriminant function for the prognosis of sepsis was developed by IL-6 and IL-10
      at different heart rates. RESULTS: IL-6 elevated continuously with the increment
      of the heart rate in the non-survival group, but in the survival group, the IL-6
      elevation started to fall when the heart rate reached 1.25 times; a similar trend
      was found in the change of IL-10. The prediction rate was 68.33% when the heart
      rate reached 1.15 times, and increased to 93.33% and 95.45% when heart rates
      reached 1.25 and 1.35 times, respectively. CONCLUSION: This linear discriminant
      function developed on the basis of IL-6 and IL-10 might be adopted as a simple
      and reliable indicator and further become a critical tool for the outcome
      prediction of sepsis.

PMID- 16297405
TI  - Knocking out answers to diabetes: role of SSTR5.

PMID- 16297407
TI  - Effect of the combination of fibrin glue and growth hormone on incomplete
      intestinal anastomoses in a rat model of intra-abdominal sepsis.
AB  - BACKGROUND: The presence of established intra-abdominal sepsis has been
      considered a contraindication to primary anastomoses. Our hypothesis was that
      fibrin glue (FG), growth hormone (rhGH), and combination of them synergistically
      improve intestinal primary anastomotic healing in a rat model of intestinal
      fistulae with peritonitis. MATERIALS AND METHODS: Male Wistar rats, induced
      intestinal fistulae with peritonitis after 24 h, were performed an enterectomy
      and intestinal anastomoses. Group A, rats (n = 60) had a complete anastomoses
      (end-to-end single layer anastomoses using 12 inverted interrupted 6-0 sutures)
      without peritonitis, group B, rats (n = 60) had a complete anastomoses after 24 h
      of peritonitis, group C rats had an incomplete anastomoses (four inverted
      interrupted sutures), groups D, E, F rats (n = 60) received FG, rhGH, or both of
      them, respectively. rhGH was given daily for 5 days. Anastomoses indicated the
      anastomotic bursting pressure (ABP), tensile strength, and hydroxyproline
      content, were determined. RESULTS: On POD 1, ABP of group C and group D was
      significantly lower than that of other groups (P < 0.01); On POD 3, ABP could not
      be determined because of intestinal dehiscence in groups C and E, ABP was
      significantly higher in groups D and F than that of groups A and B (P < 0.01);
      the ABP increased after 5 days of operation in groups A, B, and F. At the same
      time, that of group D decreased (P < 0.01). On POD 5, the tensile strength was
      significantly higher in groups A, D, and F than that in groups C, and E. On POD
      5, hydroxyproline content was higher in groups D and F compared to that in group
      C (P < 0.05). CONCLUSIONS: These data suggested that FG improve intestinal
      primary anastomotic healing within post-operative 5 days in a rat model of
      intestinal fistulae with peritonitis. RhGH alone fails to improve intestinal
      anastomotic healing, and the combination of FG and rhGH have no synergistic
      effect to improves intestinal anastomotic healing.

PMID- 16297406
TI  - Age effect on HSP70: decreased resistance to ischemic and oxidative stress in
      HDF.
AB  - BACKGROUND: Heat pre-conditioning results in induction of heat shock proteins
      including HSP70 that gives a cytoprotective effect against further stress.
      However, HSP70 induction is attenuated in aged cells. The lower HSP70-levels may
      contribute to the impaired stress response seen in the aged, and to the higher
      rates of chronic wounds in aged, which arise from repeated ischemia-reperfusion
      injury. The aim of this study was to investigate a possible connection by
      comparing the viability of heat pre-conditioned aged versus young human dermal
      fibroblasts (HDF) after exposure to stress. MATERIALS AND METHODS: Young (15-28)
      and aged (61-77) HDF were heat pre-conditioned (42 degrees C, 1 h) and after
      recovery (1, 2, or 20 h) treated with carbonyl-cyanide-m-chlorophenylhydrazone
      (hypoxic stress) or with hydrogen peroxide (oxidative stress) for 1 h. HSP70
      levels were determined by Western blot. Cell damage was assessed by quantifying
      lactic dehydrogenase (LDH) in conditioned media. Aged HDF were transfected with
      HSP70-plasmid, consecutively heat pre-conditioned and exposed to oxidative
      stress. RESULTS: HSP70 increased in heat pre-conditioned young HDF by 96, 189,
      and 237% after 1, 2, and 20-h recovery, respectively, and in aged HDF by 27, 61,
      and 26%. LDH-release was only decreased in young HDF 20-h after heat-treatment
      compared with non-heat treated cells (P < 0.001). HSP70-transfection of aged HDF
      with plasmid reduced LDH-release by 29%. CONCLUSIONS: Heat pre-conditioning fails
      to protect aged HDF to oxidative or hypoxic stress due in part to impaired HSP70
      induction compared to young.

PMID- 16297409
TI  - A case of hearing loss and quadriplegia after a pontine hemorrhage.
AB  - We herein describe the case of a 50-year-old female who developed a pontine
      hemorrhage with consciousness disturbance and quadriplegia. Her respiratory
      condition was so bad that she needed to be intubated and put on artificial
      respiration. After her consciousness and respiratory condition gradually
      recovered, we noticed that she had developed a bilateral hearing loss. The
      auditory brain stem response test revealed only I waves on both sides, thus
      suggesting that her hearing loss had been caused by an injury to the hearing
      conducting pathway including the cochlear nuclei. In this case, the hematoma
      extended from the lower to the upper part of pons and, furthermore, it was also
      located broadly in the dorsal part of the pons. As a result, the cochlear nuclei
      and corpus trapezoideum appeared to have been destroyed by the hematoma. However,
      since most cases with a brain stem hemorrhage showing bilateral hearing loss tend
      to be in a severe condition, this condition is often easy to overlook. We should
      therefore carefully evaluate patients' reaction to hearing stimulation to avoid
      overlooking any hearing loss in such patients.

PMID- 16297408
TI  - Engraftment of mucosal stem cells into murine jejunum is dependent on optimal
      dose of cells.
AB  - BACKGROUND: Transplantation of intestinal mucosal stem cells is an important step
      in the development of intestinal gene therapy and treatment of intestinal mucosal
      diseases. We hypothesized that engraftment rates increase proportionally with
      increasing doses of seeded stem cells and increasing jejunal debridment.
      MATERIALS AND METHODS: Intestinal mucosal organoids were harvested from neonatal
      mice carrying a green-fluorescent protein (GFP) transgene and transplanted into
      adult GFP(-) mice (n = 66). In recipients, two jejunal segments (1.5 cm) were
      isolated with their blood circulation left intact with anastomosis of the distal
      and proximal segments to restore continuity. Debridement of native enterocytes
      was performed by perfusing luminally with ethylene diamine tetraacetc acid
      solutions for 20 min. A total of 5,000, 10,000, or 25,000 organoids were then
      seeded. Three weeks later, cross sections (n = 398) of the segments were
      evaluated for the presence of GFP(+) neomucosa using fluorescence microscopy.
      Additional segments were debrided for 30 and 40 min (n = 83). Other conditions
      were not tested because of the rate of high mortality in these experiments.
      RESULTS: The group seeded with 10,000 organoid units at 20 min showed the highest
      engraftment of GFP(+) epithelium. Engraftment was improved by increasing
      debridment times at this seeding density. Overall mortality was 70%. CONCLUSIONS:
      These findings suggest that there is an optimal seeding density of stem cell
      clusters for enhanced engraftment in this model. Mortality prohibited complete
      testing of all combinations of seeding density and debridement times.

PMID- 16297411
TI  - Phosphodiesterase type 5 inhibitor sildenafil citrate does not potentiate the
      vasodilative properties of nebivolol in rat aorta.
AB  - BACKGROUND: Sildenafil citrate (SIL) is contraindicated in patients with coronary
      heart disease who are treated with nitric oxide (NO) donators such as organic
      nitrates, as it potentiates NO-mediated vasodilation. The present study
      investigated whether SIL also affects the vasodilatory effects of nebivolol
      (NEB), a selective beta1-adrenoceptor blocker with an additional, endothelium
      dependent NO-liberating property, in comparison to the combination SIL/glycerol
      trinitrate (GTN). METHODS AND RESULTS: Experiments were performed in isolated
      vessel rings of rat aorta (Wistar rats, 8-12 weeks), which had been pre
      contracted with phenylephrine (10(-5) M). Isometric tension was measured by a
      force transducer, and cumulative concentration-response curves were obtained for
      each drug. The rank order of vasodilatory potency as measured by the
      concentration needed to achieve 50% relaxation (EC50) was GTN (0.08 microM) > SIL
      (1.25 microM) > or = NEB (3.5 microM). In the presence of both therapeutic (1 nM)
      and high (1 microM) concentrations of SIL, vasodilation of GTN was potentiated as
      indicated by a significant increase in vasodilatory potency (EC50 GTN + low SIL:
      0.019 microM, EC50 GTN + high SIL: 0.002 microM; both P < 0.01 vs. GTN). In
      contrast, SIL did not potentiate the vasodilatory effect of NEB (EC50 NEB + low
      SIL: 5.01 microM, EC50 NEB + high SIL: 3.2 microM; n.s. vs. NEB). CONCLUSIONS:
      These data demonstrate that SIL does not potentiate NEB-induced vasodilation in
      vitro. These findings indicate that the interaction between SIL and NO
      donators/organic nitrates does not apply to the NO-liberating properties of NEB.
      Our findings suggest that SIL may safely be used in hypertensive patients treated
      with NEB.

PMID- 16297410
TI  - Metoprolol reduces 'compensatory' coronary blood flow following occlusion of an
      adjacent branch without altering post-occlusion hyperaemia.
AB  - In pentobarbitone anaesthetised, thoracotomised dogs, blood flow in one
      (circumflex; LCX) branch of the left coronary artery increases when an adjacent
      (anterior descending; LAD) branch is occluded. We show that this 'compensatory
      blood flow' increase results from an enhanced regional myocardial contractility,
      as assessed using piezoelectric crystals, and that this is to compensate for a
      marked decrease in segmental shortening (SS) in the region supplied by the
      occluded vessel. These changes in regional contractility are relatively
      unaffected by the intravenous administration of metoprolol whereas the LCX flow
      change is markedly reduced, suggesting a major contribution of coronary vascular
      beta(1)-adrenoceptors to such 'compensatory' flow changes.

PMID- 16297413
TI  - Inhibition of male chick phenotypes and spermatogenesis by Bisphenol-A.
AB  - Bisphenol-A (BPA) has been reported to bind to the estrogen receptor (ER) and
      also to act as a xenoestrogen on the reproductive system of many species. In our
      previous study, a high dose of BPA disturbed the growth of the comb and testes of
      male chickens. In this study, the exposure of relatively low doses of BPA on the
      growth of the male chicken phenotypes was investigated. White Leghorn male chicks
      were orally administered various doses of BPA (2 microg to 200 mg/kg) from 2
      weeks of age, and thereafter the comb, wattle and testes were examined at 5, 10,
      15, 20 and 25 weeks of age. Although the body weight showed no significant
      difference among the birds of all ages, the growth of above organs was
      significantly affected in the chicks even with a minimal dose of 2-microg BPA.
      These inhibitory effects appeared in a dose-dependent manner. Histologically, the
      growth of the testes was negatively affected by exposure to over 20-microg/kg
      BPA: namely, the development of seminiferous tubuli and spermatogenesis were
      severely inhibited. The mRNA expressions of ERalpha and the aromatase gene
      (p450arom) increased in the testes in a dose-dependent manner after BPA
      administration. Accordingly, even low doses of BPA delayed the growth of the male
      chicken phenotype either by a direct effect or by an indirect response resulting
      in an increase in both of the endogenous estrogen levels and hyper-sensitivity to
      estrogen.

PMID- 16297412
TI  - Curcumin modulates drug metabolizing enzymes in the female Swiss Webster mouse.
AB  - Curcumin, the yellow pigment found in turmeric, exhibits potent chemopreventative
      properties in both in vivo and in vitro cancer models. We hypothesized that this
      effect may occur via curcumin-mediated changes in enzymes involved in both
      carcinogen bioactivation and estrogen metabolism. Female Swiss Webster mice were
      treated with either curcumin (200 mg/kg or 400 mg/kg, p.o.) or vehicle control
      for 1 or 2 weeks. The results demonstrated that curcumin had no effect on the
      catalytic activities of ovarian aromatase, hepatic catechol-O-methyltransferase
      or hepatic UDP-glucuronosyltransferase. However, both doses of curcumin caused a
      25% decrease in CYP1A catalytic activity, but not polypeptide levels, following 2
      weeks of treatment. Additionally, following 2 weeks of curcumin at 400 mg/kg,
      there was a 20% decrease in the catalytic activity and a 28% decrease in
      polypeptide levels of CYP3A. While 2 weeks of curcumin treatment (400 mg/kg)
      caused a 20% increase in glutathione S-transferase activity, there was no
      parallel increase in hepatic stores of the co-factor glutathione. In conclusion
      small changes in CYP1A, CYP3A and GST following long term treatment (2 weeks)
      suggest that the combination of all three metabolic pathways may play a small
      role in curcumin's chemopreventative action.

PMID- 16297415
TI  - The 2003 SARS outbreak and its impact on infection control practices.
AB  - Severe Acute Respiratory Syndrome (SARS) emerged recently as a new infectious
      disease that was transmitted efficiently in the healthcare setting and
      particularly affected healthcare workers (HCWs), patients and visitors. The
      efficiency of transmission within healthcare facilities was recognised following
      significant hospital outbreaks of SARS in Canada, China, Hong Kong, Singapore,
      Taiwan and Vietnam. The causative agent of SARS was identified as a novel
      coronavirus, the SARS coronavirus. This was largely spread by direct or indirect
      contact with large respiratory droplets, although airborne transmission has also
      been reported. High infection rates among HCWs led initially to the theory that
      SARS was highly contagious and the concept of 'super-spreading events'. Such
      events illustrated that lack of infection control (IC) measures or failure to
      comply with IC precautions could lead to large-scale hospital outbreaks. SARS was
      eventually contained by the stringent application of IC measures that limited
      exposure of HCWs to potentially infectious individuals. As the 'global village'
      becomes smaller and other microbial threats to health emerge, or re-emerge, there
      is an urgent need to develop a global strategy for infection control in
      hospitals. This paper provides an overview of the main IC practices employed
      during the 2003 SARS outbreak, including management measures, dedicated SARS
      hospitals, personal protective equipment, isolation, handwashing, environmental
      decontamination, education and training. The psychological and psychosocial
      impact on HCWs during the outbreak are also discussed. Requirements for IC
      programmes in the post-SARS period are proposed based on the major lessons learnt
      from the SARS outbreak.

PMID- 16297414
TI  - Flavonoids in flowers of 16 Kalanchoe blossfeldiana varieties.
AB  - Kalanchoe blossfeldiana varieties with orange, pink, red and magenta flowers were
      found to contain 3,5-O-beta-D-diglucosides of pelargonidin, cyanidin, peonidin,
      delphinidin, petunidin and malvidin. Pink, red and magenta varieties contained
      relatively high amounts of quercetin based flavonols. Four distinct quercetin
      flavonols were identified, namely quercetin 3-O-beta-D-glucoside and three that
      were quercetin 3-O-alpha-L-rhamnoside based, with either glucose, xylose or
      arabinose attached to position 2 of the rhamnose. In addition, the presence of at
      least three kaempferol based diglycosides was suggested from LC-MS analyses.
      Orange varieties contained very low amounts of flavonol co-pigments and of
      delphinidin derivatives. The flower extracts of the varieties 'Diva' (magenta)
      and 'Molly' (red) had identical anthocyanin ratios but differed significantly in
      flavonol content. The magenta variety contained four times as much quercetin
      relative to anthocyanidin as the red variety. This difference was mainly due to a
      larger content of quercetin 3-O-(2''-O-beta-D-glucopyranosyl-alpha-L
      rhamnopyranoside). Based on pigment and co-pigment analyses, approaches for
      molecular breeding towards blue flower colour are discussed.

PMID- 16297416
TI  - Public health measures implemented during the SARS outbreak in Singapore, 2003.
AB  - The SARS outbreak hit Singapore between March and May 2003. Public health control
      measures were applied along three fronts; prevention and control within
      healthcare settings, community and at the borders. Nosocomial spread composed
      majority of SARS cases in Singapore. To prevent infection within healthcare
      facilities, cases were centralized in a SARS-designated hospital, a no-visitors
      rule was applied and movement of patients and healthcare staff were restricted.
      For triaging purposes, fever clinics were established. A dedicated ambulance
      service was used to transport possible cases to the SARS-designated hospital.
      Hospitals were surveyed for fever clusters. The challenge was to identify cases
      with atypical presentation. Effective and safe discharge criteria were
      established from the lessons learnt. To prevent community spread, contacts of
      cases were stringently traced, quarantined in their homes and monitored daily.
      For prompt identification of a case and to reduce the time between onset of
      symptoms and isolation, the Infectious Diseases Act was amended. A large
      wholesale market closure resulted in massive quarantine thereby limiting the
      spread of infection. A mass education campaign was implemented in order to
      educate and raise awareness of the public. At all air, sea and land points-of
      entry, exit and entry screening took place that resulted in zero importation and
      exportation of SARS cases after implementation of screening. Coordinated effort
      of the cross sectional inter-ministerial collaboration and strong coordination by
      the Task Force and commitment from different professionals made it possible to
      conquer the disease.

PMID- 16297417
TI  - Lessons learned from SARS: the experience of the Health Protection Agency,
      England.
AB  - The United Kingdom was assessed as a low risk country throughout the 2003 global
      SARS outbreaks. Despite this, 368 reports of potential SARS cases were made to
      the Health Protection Agency (HPA) between March and July 2003. The public health
      actions undertaken in response to these reports, the establishment of reporting
      mechanisms and the development of guidance documents were substantial. Lessons
      learned from mounting a UK response to SARS included: the importance of
      international collaboration; formation of a UK-wide, multidisciplinary Task
      Force; flexible case reporting mechanisms; integration of surveillance and
      laboratory data; generation of prompt and web-accessible guidance and advice;
      availability of surge capacity; and contingency planning. Lessons learned are
      being incorporated into the HPA's preparedness to prevent and control future
      newly emerging infectious disease threats.

PMID- 16297418
TI  - Alterations in plasma antioxidants during reperfusion of the ischemic small
      intestine in rats.
AB  - The aim of this study was to evaluate the contribution of three plasma
      antioxidants (albumin, uric acid, SH groups) to the plasma total peroxyl radical
      trapping antioxidant capacity (TRAP) in 2 and 4 h of intestinal reperfusion in
      rats. TRAP increased significantly both after 2 and 4 h of reperfusion. Neither
      albumin nor SH groups contributed significantly to this increase. TRAP was
      strongly influenced by the increase in uric acid concentration and also probably
      by the cell destruction caused by oxidative stress. Since the TRAP increase was
      accompanied by an increase in the level of thiobarbituric acid reactive
      substances (TBARS, a marker of lipid peroxidation), we can conclude that even
      such a large increase in TRAP is not sufficient to prevent the progression of
      lipid peroxidation and oxidative stress.

PMID- 16297419
TI  - Efficacy of chloroquine, sulfadoxine-pyrimethamine and amodiaquine for treatment
      of uncomplicated Plasmodium falciparum malaria among children under five in
      Bongor and Koumra, Chad.
AB  - We report two 28-day in-vivo antimalarial efficacy studies carried out in the
      urban centres of Bongor and Koumra, southern Chad. We assess chloroquine (CQ),
      sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) to treat Plasmodium
      falciparum uncomplicated malaria. Methods and outcome classification complied
      with latest WHO guidelines. Out of the 301 and 318 children aged 6-59 months
      included in Bongor and Koumra, respectively, 246 (81.7%) and 257 (80.8%) were
      eligible for analysis. In Bongor and Koumra, the 28-day PCR-adjusted failure
      rates for CQ were 23.7% (95% CI 14.7-34.8%) and 32.9% (95% CI 22.1-45.1%),
      respectively, and those for SP were 16.3% (95% CI 9.4-25.5%) and 4.3% (95% CI 1.2
      10.5%). AQ failure rates were 6.4% (95% CI 2.1-14.3%) and 2.2% (95% CI 0.3-7.6%).
      The current use of CQ in Bongor and Koumra is questionable, and a more
      efficacious treatment is needed. Considering the reduced efficacy of SP in
      Bongor, AQ seems to be the best option for the time being. Following WHO
      recommendations that prioritize the use of artemisinin-based combinations,
      artesunate plus amodiaquine could be a potential first-line treatment.
      Nevertheless, the efficacy of this combination should be evaluated and the change
      carefully prepared, implemented and monitored.

PMID- 16297420
TI  - Rapid inhibitory effect of glucocorticoids on airway smooth muscle contractions
      in guinea pigs.
AB  - The common disease asthma is characterized by the obstruction, inflammation and
      increased sensitivity of the airways. Glucocorticoids (GCs) are one of the most
      potent anti-inflammatory agents available for treating allergic disease. In this
      study, we report that the GC budesonide (BUD) can rapidly inhibit the histamine
      induced contractions of airway smooth muscle in a process mediated by non-genomic
      mechanisms. The tracheas of albino Hartley guinea pigs were used. We measured the
      effects of BUD on the increased isometric tension of trachea segment rings and
      the shrinking of single airway smooth muscle cells (ASMCs) induced by histamine.
      With the application of each reagent, the changes in the isometric tension of the
      segment rings upon maximum contraction and at four time points were recorded. We
      found that BUD significantly suppressed the increase in isometric tension induced
      by histamine in guinea pigs within 15 min. We also observed that BUD can reduce
      the histamine-induced shrinking of single ASMCs in an even shorter time.
      Mifepristone (RU486) and actidione did not depress the inhibitory effect of BUD.
      The results preclude action via genomic-mediated responses that usually take
      several hours to occur. We conclude therefore that GCs have a rapid non-genomic
      inhibitory effect on guinea pig airway smooth muscle contractions, and provide a
      new way to investigate this non-genomic mechanism. Further study can provide
      theoretical evidence for the clinical application of GCs in asthma and other
      allergic diseases.

PMID- 16297421
TI  - Characterization of MNAR expression.
AB  - We have previously demonstrated that modulator of nongenomic action of estrogen
      receptor (MNAR) integrates action of estrogen receptor alpha (ERalpha), and
      potentially some other nuclear receptors (NRs), in regulation of
      Src/Ras/Raf/mitogen-activated protein kinase (MAPK) signaling pathway. MNAR is a
      scaffolding protein that contains 10 LXXLL type motifs that can interact with NRs
      and 3 PXXP type motifs that can bind to SH3 domains present in kinases and other
      signaling molecules. Formation of ER-MNAR-cSrc complex leads to activation of Src
      and downstream Ras/Raf/MAPK pathway. The goal for this study was to compare MNAR
      expression in various cell lines, to optimize methods that can be used to
      manipulate its expression and to evaluate MNAR cellular distribution. We found
      that MNAR is differentially expressed. The highest levels of its expression were
      found in fast proliferating cells, such as breast adenocarcinoma (MCF-7)-, T cell
      lymphoma (Jurkat)-, prostate carcinoma (LNCaP)- and osteosarcoma (SaOS2)-derived
      cell lines. MNAR was undetectable in African green monkey kidney cells (COS-7)
      and Chinese hamster ovary cells (CHO-K1). We established and optimized a protocol
      to knockdown MNAR using siRNA and to overexpress it in MCF-7 cells. Exogenously
      expressed MNAR was found in both cytoplasmic and nuclear fractions, the majority
      of MNAR, however, was found in the cytoplasmic fraction. Presence of MNAR in the
      cell nucleus indicates that it may play a role in regulation of gene expression.

PMID- 16297422
TI  - Antibodies against Gag are diagnostic markers for feline foamy virus infections
      while Env and Bet reactivity is undetectable in a substantial fraction of
      infected cats.
AB  - Spumaretroviruses or foamy viruses constitute a distinct subfamily of
      retroviruses. The biology of foamy viruses within the authentic host, their mode
      of transmission, and disease potential in the authentic host or after zoonotic
      transmission into human or other species are almost unknown. Using feline foamy
      virus (FFV) as model system, we established modular enzyme-linked immunosorbent
      assays (ELISA) suited to determine feline IgG and IgM antibody responses against
      structural and non-structural FFV proteins. We validated the ELISAs with standard
      reference sera. In 99 cats admitted to a Swiss veterinary hospital, overall FFV
      Gag antibody prevalence was 36%, reactivity against Env and the non-structural
      protein Bet each was about 25%, and 19% of the sera were directed against all
      three FFV antigens. With one exception, all Bet- and/or Env-positive sera were
      also positive for Gag. In this small epidemiological pilot study, FFV antibodies
      were not significantly associated with clinical disease.

PMID- 16297423
TI  - Rescue of internal scaffold-deleted Mason-Pfizer monkey virus particle production
      by plasma membrane targeting.
AB  - The Mason-Pfizer monkey virus (M-PMV) Gag protein follows a morphogenesis pathway
      in which immature capsids are preassembled within the cytoplasm before
      interaction with and budding through the plasma membrane. Intracytoplasmic
      assembly is facilitated by sequences within the p12 domain of Gag that we have
      termed the Internal Scaffold Domain (ISD). If M-PMV utilizes an ISD then what
      provides the equivalent function for most other retroviruses that assemble at the
      plasma membrane? To investigate the possibility that the membrane itself fulfills
      this role, we have combined functional deletion of the ISD with a mutation that
      disrupts intracellular targeting or with a plasma membrane targeting signal. By
      either modification, targeting of ISD-deleted Gag to the plasma membrane restores
      particle production. These results provide support for a model in which the
      plasma membrane and the D-type ISD provide an interchangeable scaffold-like
      function in retrovirus assembly.

PMID- 16297425
TI  - Relationship between poliovirus negative-strand RNA synthesis and the length of
      the 3' poly(A) tail.
AB  - The precise relationship between the length of the 3' poly(A) tail and the
      replication and infectivity of poliovirus RNA was examined in this study. With
      both poly(A)(11) and poly(A)(12) RNAs, negative-strand synthesis was 1-3% of the
      level observed with poly(A)(80) RNA. In contrast, increasing the length of the
      poly(A) tail from (A)(12) to (A)(13) resulted in about a ten-fold increase in
      negative-strand synthesis. This increase continued with each successive increase
      in poly(A) tail length. With poly(A)(20) RNA, RNA synthesis approached the level
      observed with poly(A)(80) RNA. A similar relationship was observed between
      poly(A) tail length and the infectivity of the viral RNA. A replication model is
      described which suggests that viral RNA replication is dependent on a poly(A)
      tail that is long enough to bind poly(A) binding protein and to act as a template
      for VPg uridylylation and negative-strand initiation.

PMID- 16297424
TI  - Interaction between a 1998 human influenza virus N2 neuraminidase and monoclonal
      antibody Mem5.
AB  - Influenza virus constantly escapes antibody inhibition by introducing mutations
      that disrupt protein-protein interactions. Based on the structure of the complex
      between neuraminidase (NA) of influenza A/Memphis/31/98 (H3N2) and the Fab of a
      monoclonal antibody (Mem5) that binds and inhibits the Memphis/98 NA, we
      investigated the contribution made by individual amino acids of NA to the
      stability of the complex. We made mutations D147A, D147N, H150A, H197A, D198A,
      D198N, E199A, E199Q, K221R, A246K, D251N, and D251A. Binding of each mutant to NA
      was quantitated by NA inhibition assays and ELISA. Most of the mutant NAs were
      inhibited by Mem5 to the same extent as wild-type, but with lower affinity. The
      exceptions were E199A, E199Q, and K221R, in which binding was abrogated. The
      ELISA results confirmed a correlation between NA inhibition and binding. The Mem5
      epitope is dominated by a few high-energy interactions as was found in the
      epitope on an avian subtype N9 NA that binds antibody NC41 and different to the
      more diffuse energy distribution in the NC10 epitope on N9 NA. Energetic
      dominance of a particular interaction, which is associated with potential for
      antibody escape mutations, may be associated with the absence of water molecules
      in the vicinity. Critical contacts in a dominant antigenic site are likely to
      mutate, allowing some predictions of antigenic drift.

PMID- 16297426
TI  - The role of the 3' terminus of the Sindbis virus genome in minus-strand
      initiation site selection.
AB  - Genome replication of plus-strand RNA viruses begins with the generation of a
      minus-strand copy of the genome. Minus-strand synthesis must initiate at or close
      to the 3' end of the genome and progress to processive elongation to yield the
      appropriate template for genomic RNA synthesis. The Sindbis virus genome
      possesses a 3' polyadenylate tail preceded by a 19 nucleotide conserved sequence
      element (3' CSE). Analyses of in vitro and in vivo synthesized minus-strand RNA
      presented in this manuscript identify the cytidylate residue immediately
      preceding the poly (A) tail as the predominant wild-type initiation site.
      Mutations in the poly (A) tail and the 3' CSE caused the initiation site to shift
      to the poly (A) tail. Analysis of the products of non-wild-type initiation events
      demonstrated that they are not productively elongated. This study indicates that
      full-length minus-strand RNA synthesis is dependent upon initiation occurring at
      the appropriate site and suggests a mechanism for selection and maintenance of
      the wt 3' CSE and poly (A) tail.

PMID- 16297427
TI  - Estimating biodegradation half-lives for use in chemical screening.
AB  - Biodegradation half-lives are needed for many applications in chemical screening,
      but these data are not available for most chemicals. To address this, in phase
      one of this work we correlated the much more abundant ready and inherent
      biodegradation test data with measured half-lives for water and soil. In phase
      two, we explored the utility of the BIOWIN models (in EPI Suite) and molecular
      fragments for predicting half-lives. BIOWIN model output was correlated directly
      with measured half-lives, and new models were developed by re-regressing the
      BIOWIN fragments against the half-lives. All of these approaches gave the best
      results when used for binary (fast/slow) classification of half-lives, with
      accuracy generally in the 70-80% range. In the last phase, we used the collected
      half-life data to examine the default half-lives assigned by EPI Suite and the
      PBT Profiler for use as input to their level III multimedia models. It is
      concluded that estimated half-lives should not be used for purposes other than
      binning or prioritizing chemicals unless accuracy improves significantly.

PMID- 16297428
TI  - Comparative use of bacterial, algal and protozoan tests to study toxicity of azo-
      and anthraquinone dyes.
AB  - Toxicity of two azo dyes (Reactive Orange 16 (RO16); Congo Red (CR)) and two
      anthraquinone dyes (Remazol Brilliant Blue R (RBBR); Disperse Blue 3 (DB3)) were
      compared using bacterium Vibrio fischeri, microalga Selenastrum capricornutum and
      ciliate Tetrahymena pyriformis. The following respective endpoints were involved:
      acute toxicity measured as bacterial luminescence inhibition, algal growth
      inhibition, and the effects on the protozoa including viability, growth
      inhibition, grazing effect and morphometric effects. In addition, mutagenicity of
      the dyes was determined using Ames test with bacterium Salmonella typhimurium
      His(-). DB3 dye was the most toxic of all dyes in the bacterial, algal and
      protozoan tests. In contrast to other dyes, DB3 exhibited mutagenic effects after
      metabolic activation in vitro in all S. typhimurium strains used. Of the methods
      applied, the algal test was the most sensitive to evaluate toxicity of the dyes
      tested.

PMID- 16297429
TI  - Residues of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls
      (PCBs) and organochlorine pesticides in organically-farmed vegetables.
AB  - The residues of polyaromatic hydrocarbons (PAHs), polychlorinated biphenyls
      (PCBs) and organochlorine pesticides (OCPs) in soils from organic farms and their
      uptake by four varieties of organic-produced potatoes and three varieties of
      organic carrots from England were investigated. Samples of the soils, crop peels
      and cores were all Soxhlet-extracted in triplicate, cleaned up by open-column
      chromatography and analysed by a multi-residue analytical method using gas
      chromatography with mass selective detection. The concentrations of PAHs, PCBs
      and OCPs in soils from organic farms ranged from 590+/-43 to 2301+/-146
      microg/kg, 3.56+/-0.73 to 9.61+/-1.98 microg/kg and 52.2+/-4.9 to 478+/-111
      microg/kg, respectively. Uptake by different crop varieties were 8.42+/-0.93 to
      40.1+/-4.9 microg/kg sigmaPAHs, 0.83+/-0.19 to 2.68+/-0.94 microg/kg sigmaPCBs
      and 8.09+/-0.83 to 133+/-27 microg/kg sigmaOCPs. Residue uptake from soils
      depended on plant variety; Desiree potato and Nairobi carrot varieties were more
      susceptible to PAH contamination. Likewise, uptake of PCBs and OCPs depended on
      potato variety. There were significant positive correlations between the PCB and
      OCP concentrations (P<0.05) in soils and carrots but no significant correlation
      was found between the concentrations of any contaminants in soils and potatoes.
      Peeling carrots and potatoes was found to remove 52-100% of the contaminant
      residues depending on crop variety and the properties of the contaminants. Soil
      crop bioconcentration factors (BCFs) decreased with increasing logK(ow) for PAHs
      up to about 4.5 and for PCBs up to about 6.5, above which no changes were
      discernible for either class of contaminants. No relationship was observed
      between soil-crop BCFs and logK(ow) for OCPs, most likely because their
      concentrations were low and variable.

PMID- 16297430
TI  - Simultaneous photocatalytic reduction of Cr(VI) and oxidation of phenol over
      monoclinic BiVO4 under visible light irradiation.
AB  - BiVO4 powder with monoclinic structure was prepared and used as a visible-light
      catalyst simultaneously for the photooxidation of phenol and the photoreduction
      of Cr(VI). The photocatalytic efficiency was found to be rather low for either
      single phenol solution or single Cr(VI) solution. However, the photocatalytic
      reduction of Cr(VI) and photocatalytic oxidation of phenol proceed more rapidly
      for the coexistence system of phenol and Cr(VI) than for the single process,
      showing synergetic effect between the oxidation and reduction reactions. For the
      simultaneous photocatalytic reduction-oxidation process, the first-order kinetic
      constant of phenol degradation was 0.0314 min-1, being about six times higher
      than that for the photocatalytic process of single phenol. This result reveals
      the feasibility of using Cr(VI) as the electron scavenger of mBiVO4-mediated
      photocatalytic process of phenol degradation, and gives us an enlightenment to
      employ other semiconductor with a better visible light response but with a more
      positive band edge to efficiently degrade organic pollutants. This is the first
      report for simultaneous photocatalytic reduction of Cr(VI) and removal of phenol
      under visible light irradiation using photocatalyst mBiVO4.

PMID- 16297431
TI  - Spectrophotometric determination of uranium with arsenazo-III in perchloric acid.
AB  - A short, sensitive and reliable spectrophotometric method, which has advantages
      over all known "wet chemistry" methods for uranium determination with regard to
      tolerance to common interferences, has been developed for the determination of
      uranium. Selectivity, molar absorptivity and the determination range of uranium
      have been enhanced by using 0.07% arsenazo-III as a chromogenic reagent. The use
      of 3 mol dm(-3) perchloric acid as a medium of determination was found to be
      excellent in terms of good solvent compatibility on dilution, destruction of
      organic contamination and simplicity of operation. The uranium-arsenazo-III
      complex formed instantly, and was found to be stable for more than 3 weeks with
      constant absorbance. Beer's law was obeyed up to a uranium concentration of 16
      microg g(-1), with a molar absorptivity at 651 nm of 1.45x10(5) mol(-1) dm(3) cm(
      1) at 24+/-2 degrees C. Only phosphate and citrate at 70-fold excess over uranium
      interfere seriously, whereas other anions studied could be tolerated up to a 70
      fold excess over uranium. Of the cations studied, only Mn(II), Co(II), Ni(II),
      Cu(II) and Cr(III) decreased the normal absorbance of the complex. Iron(III),
      Ce(III) and Y(III) enhanced the absorbance. Other cations studied did not affect
      the absorbance up to a 50-fold excess. The accuracy was checked by determining
      uranium from standard solutions in the range 10-50 microg g(-1). It was found to
      be accurate with a 96.0-98.6% recovery rate. The method has been successfully
      applied to standard reference materials and ore samples at microg g(-1) levels.

PMID- 16297432
TI  - Formation of hazardous by-products resulting from the irradiation of natural
      organic matter: comparison between UV and VUV irradiation.
AB  - The use of ultraviolet (UV) or vacuum ultraviolet (VUV) photo-oxidation followed
      by biological treatment for the removal of natural organic matter (NOM) in
      drinking water is a potential water treatment technique under investigation. This
      paper reports on the trihalomethane formation potential (THMFP), the haloacetic
      acid formation potential (HAAFP), and formation of nitrite and peroxide following
      both UV and VUV irradiation of NOM prior to biological treatment. The total THMFP
      was found to decrease with increasing UV and VUV irradiation dose, although there
      was a linear increase in bromoform formation. Determination of the THMFP of NOM
      fractions obtained after irradiation, showed that the hydrophobic fraction was
      dominated by chlorinated species which accounted for the majority of the total
      THMFP, while bromoform was observed only in the hydrophilic fraction of NOM. VUV
      irradiation reduced the HAAFP with increasing dose, in contrast, UV irradiation
      had a limited effect on the overall HAAFP. Following UV or VUV irradiation, the
      chlorinated species accounted for the majority of HAAFP; however, significant
      formation of brominated haloacetic acid (HAA) was observed. The nitrate
      concentration of the untreated water directly influenced the concentration of
      nitrite produced as a consequence of UV and VUV irradiation. Hydrogen peroxide
      formation was greater during VUV irradiation than during UV irradiation. Samples
      exposed to various doses of UV or VUV irradiation (up to 138 J cm(-2)) were
      deemed non-cytotoxic (African green monkey kidney cells) and non-mutagenic (Ames
      test).

PMID- 16297433
TI  - Transplacental transfer of butyltins to fetus of Dall's porpoises (Phocoenoides
      dalli).
AB  - Here we provided evidence, for the first time, on the placental transfer of
      butyltin species in Dall's porpoise (Phocoenoides dalli). The maternal to fetal
      transfer of butyltins including monobutyltin (MBT), dibutyltin (DBT) and
      tributyltin (TBT) was investigated in a mother-fetus pair collected off the
      Sanriku coast of Japan. The maternal individual was found contaminated as its
      liver accumulated the highest concentrations of all MBT, DBT and TBT. This study
      revealed that the transfer rate was about 0.3% for total butyltins to a fetus of
      about 6 months old. Unlike in the mother, the fetal liver does not appear to be a
      preferential organ for accumulation of all the butyltins. In a approximately 100
      kg-weight mother Dall's porpoise and its fetus of 2.21 kg-weight about 1,269
      microg (TBT, 578 microg; DBT, 480 microg; MBT, 211 microg) and 4.2 microg of
      total butyltins (TBT, 1.1 microg; DBT, 2.1 microg; MBT, 0.96 microg) were found,
      respectively.

PMID- 16297434
TI  - Neurotransmitter deficits in behavioural and psychological symptoms of
      Alzheimer's disease.
AB  - Behavioural and psychological symptoms of dementia (BPSD) occur in 50-90% of
      Alzheimer's disease (AD) patients. Imbalance of different neurotransmitters
      (acetylcholine, dopamine, noradrenaline and serotonin), involvement of specific
      brain regions responsible for emotional activities (parahippocampal gyrus, dorsal
      raphe and locus coeruleus) and cortical hypometabolism have been proposed as
      neurobiological substrate of BPSD. Compared to with respect to the neurochemical
      component, the cholinergic dysfunction seems to play a major role in contributing
      to BPSD occurrence. This view is also supported by the findings of recent trials
      with cholinesterase inhibitors, showing that these drugs are effective in
      controlling and/or improving BPSD, independent on effects on cognitive
      dysfunction. On the site of psychotropic drugs, atypical or novel antipsychotics
      represent the reference drugs for treating BPSD, whereas classic antipsychotic
      drugs for their profile and the potential side effects should be avoided.

PMID- 16297435
TI  - Association with the cholinergic precursor choline alphoscerate and the
      cholinesterase inhibitor rivastigmine: an approach for enhancing cholinergic
      neurotransmission.
AB  - The effects of association of cholinergic precursors choline or choline
      alphoscerate with the cholinesterase inhibitor rivastigmine on acetylcholine
      levels and [(3)H]hemicholinium-3 binding were assessed in rat frontal cortex,
      hippocampus and striatum. Acetylcholine immunoreactivity was also evaluated in
      cerebrocortical cholinergic fibers by immunohistochemistry. Choline alphoscerate
      or rivastigmine, but not choline increased acetylcholine levels as well as
      [(3)H]hemicholinium-3 binding used as a marker of high affinity cholinergic
      transporter. The association of choline alphoscerate with rivastigmine dose
      dependently increased both acetylcholine levels and [(3)H]hemicholinium-3
      binding. Rivastigmine alone or in association with either choline or choline
      alphoscerate decreased acetylcholinesterase (AChE), whereas choline or choline
      alphoscerate alone did not affect AChE activity. Choline alphoscerate or
      rivastigmine alone or in association, but not choline increased acetylcholine
      immunoreactivity in nerve fibers supplying cerebral cortex. These data suggest
      that combination of a suitable precursor of brain acetylcholine such as choline
      alphoscerate and of a cholinesterase inhibitor may represent an association
      worthwhile of being further investigated as a cholinergic replacement therapy in
      pathologies characterized by altered cholinergic neurotransmission.

PMID- 16297436
TI  - Pathophysiology of synuclein aggregation in Lewy body disease.
AB  - We provide an overview of synaptic pathology in dementia with Lewy bodies (DLB)
      and related neurodegenerative disorders that are characterised by intraneuronal
      accumulation of alpha-synuclein aggregates. The review addresses the clinico
      neuropathological correlates of synaptic pathology in Lewy body disease, and
      concentrates on: altered alpha-synuclein metabolism, mechanisms leading to alpha
      synuclein fibril formation (self-polymerisation, alpha-synuclein mutations and
      post-translational modifications) and how these influence the axonal transport
      and synaptic network in ageing and disease process. Understanding the mechanisms
      leading to intraneuronal alpha-synuclein accumulation are crucial for the
      development of novel therapies for treatment of Lewy body disease.

PMID- 16297437
TI  - Manganese concentrations in the air of the Montreal (Canada) subway in relation
      to surface automobile traffic density.
AB  - Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic derivative of
      manganese (Mn), used since 1976 in Canadian gasoline as an octane enhancer. Its
      combustion leads to the emission of Mn particles. Several studies carried out by
      our research group have established a correlation between atmospheric Mn
      concentrations and automobile traffic density, suggesting that MMT in gasoline
      could play a significant role. This study aims to measure Mn concentrations in
      the air of the underground subway in Montreal (Canada) and to examine the
      relation with nearby surface automobile traffic density and, by extension, with
      the use of MMT in gasoline. Three subway stations were chosen for their location
      in different microenvironments with different traffic densities. Respirable
      (MnR<5 microm) and total Mn (MnT) were sampled over two weeks, 5 days/week, 12
      h/day. For the station located in the lower traffic density area, relatively low
      levels of MnR and MnT were found, with averages of 0.018 and 0.032 microg/m(3),
      respectively. These concentrations are within the range of the background levels
      in Montreal. For the other two stations, the average concentrations of MnR were
      twice as high and exceeded the US EPA reference concentration of 0.05
      microg/m(3). Although there may be several sources of Mn from different
      components of the subway structure and vehicles, no correlation was found between
      subway traffic and atmospheric Mn in the subway. Since the air in the underground
      subway is pumped directly from outside without filtration, our findings strongly
      suggest that the combustion of MMT in automobiles is an important factor.

PMID- 16297438
TI  - Human health implications of environmental contaminants in Arctic Canada: A
      review.
AB  - The objectives of this paper are to: assess the impact of exposure to current
      levels of environmental contaminants in the Canadian Arctic on human health;
      identify the data and knowledge gaps that need to be filled by future human
      health research and monitoring; examine how these issues have changed since our
      first assessment [Van Oostdam, J., Gilman, A., Dewailly, E., Usher, P., Wheatley,
      B., Kuhnlein, H. et al., 1999. Human health implications of environmental
      contaminants in Arctic Canada: a review. Sci Total Environ 230, 1-82]. The
      primary exposure pathway for contaminants for various organochlorines (OCs) and
      toxic metals is through the traditional northern diet. Exposures tend to be
      higher in the eastern than the western Canadian Arctic. In recent dietary surveys
      among five Inuit regions, mean intakes by 20- to 40-year-old adults in Baffin,
      Kivalliq and Inuvialuit communities exceeded the provisional tolerable daily
      intakes (pTDIs) for the OCs, chlordane and toxaphene. The most recent findings in
      NWT and Nunavut indicate that almost half of the blood samples from Inuit mothers
      exceeded the level of concern value of 5 microg/L for PCBs, but none exceeded the
      action level of 100 microg/L. For Dene/Metis and Caucasians of the Northwest
      Territories exposure to OCs are mostly below this level of concern. Based on the
      exceedances of the pTDI and of various blood guidelines, mercury and to a lesser
      extent lead (from the use of lead shot in hunting game) are also concerns among
      Arctic peoples. The developing foetus is likely to be more sensitive to the
      effects of OCs and metals than adults, and is the age groups of greatest risk in
      the Arctic. Studies of infant development in Nunavik have linked deficits in
      immune function, an increase in childhood respiratory infections and birth weight
      to prenatal exposure to OCs. Balancing the risks and benefits of a diet of
      country foods is very difficult. The nutritional benefits of country food and its
      contribution to the total diet are substantial. Country food contributes
      significantly more protein, iron and zinc to the diets of consumers than
      southern/market foods. The increase in obesity, diabetes and cardiovascular
      disease has been linked to a shift away from a country food diet and a less
      active lifestyle. These foods are an integral component of good health among
      Aboriginal peoples. The social, cultural, spiritual, nutritional and economic
      benefits of these foods must be considered in concert with the risks of exposure
      to environmental contaminants through their exposure. Consequently, the
      contamination of country food raises problems which go far beyond the usual
      confines of public health and cannot be resolved simply by risk-based health
      advisories or food substitutions alone. All decisions should involve the
      community and consider many aspects of socio-cultural stability to arrive at a
      decision that will be the most protective and least detrimental to the
      communities.

PMID- 16297439
TI  - Calculation and mapping of critical loads of sulphur and nitrogen for forest
      soils in Galicia (NW Spain).
AB  - Calculations of critical loads of acidity within Europe have shown Galicia to be
      one of the regions in Spain with the highest risk of soil acidification by
      deposition of atmospheric pollutants. We used the simple mass balance method
      (SMB) to derive critical loads of sulphur and nitrogen for forest soils in
      Galicia using available site-specific information. Exceedance of acidic
      deposition was calculated using the deposition levels of N and S registered in
      2001. Most forest ecosystems analysed can support acid loads of more than 2000 eq
      N ha(-1) year(-1). The lowest critical loads of acidity (1483 eq ha(-1) year(-1))
      occurred in coniferous forest stands growing on shallow soils developed on
      slates, in the interior zone. The highest critical load values (9386 eq ha(-1)
      year(-1)) were observed in coniferous stands in zones with elevated precipitation
      rates, in the littoral area. The critical load for acidity was exceeded in 5% of
      the forest soils. Such exceedances were mainly caused by deposition of nitrogen
      compounds. The contribution of sulphur deposition to acid exceedance was
      important in the surroundings of the city of A Coruna. Analysis of rainfall bulk
      composition revealed that N deposition in Galicia was mainly due to ammonium
      emissions, probably derived from agricultural and cattle breeding activities.

PMID- 16297440
TI  - Biodiversity in urban habitat patches.
AB  - We examined the biodiversity of urban habitats in Birmingham (England) using a
      combination of field surveys of plants and carabid beetles, genetic studies of
      four species of butterflies, modelling the anthropochorous nature of the floral
      communities and spatially explicit modelling of selected mammal species. The aim
      of the project was to: (i) understand the ecological characteristics of the biota
      of cities model, (ii) examine the effects of habitat fragment size and
      connectivity upon the ecological diversity and individual species distributions,
      (iii) predict biodiversity in cities, and (iv) analyse the extent to which the
      flora and fauna utilise the 'urban greenways' both as wildlife corridors and as
      habitats in their own right. The results suggest that cities provide habitats for
      rich and diverse range of plants and animals, which occur sometimes in unlikely
      recombinant communities. The studies on carabids and butterflies illustrated the
      relative importance of habitat quality on individual sites as opposed to site
      location within the conurbation. This suggests that dispersal for most of our
      urban species is not a limiting factor in population persistence, although
      elements of the woodland carabid fauna did appear to have some geographical
      structuring. Theoretical models suggested that dormice and water voles may depend
      on linear habitats for dispersal. The models also indicated that other groups,
      such as small and medium sized mammals, may use corridors, although field-based
      research did not provide any evidence to suggest that plants or invertebrates use
      urban greenways for dispersal. This finding indicates the importance of
      identifying a target species or group of species for urban greenways intended as
      dispersal routeways rather than as habitat in their own right. Their importance
      for most groups is rather that greenways provide a chain of different habitats
      permeating the urban environment. We suggest that planners can have a positive
      impact on urban biodiversity by slowing the pace of redevelopment and by not
      hurrying to tidy up and redevelop brownfield sites.

PMID- 16297441
TI  - Behavioral differences between subgroups of rats with high and low threshold to
      clonic convulsions induced by DMCM, a benzodiazepine inverse agonist.
AB  - In epileptic patients, there is a high incidence of psychiatric comorbidities,
      such as anxiety. Gamma-aminobutyric acid (GABA) ionotropic receptor
      GABA(A)/benzodiazepine allosteric site is involved in both epilepsy and anxiety.
      This involvement is based on the fact that benzodiazepine allosteric site
      agonists are anticonvulsant and anxiolytic drugs; on the other hand,
      benzodiazepine inverse agonists are potent convulsant and anxiogenic drugs. The
      aim of this work was to determine if subgroups of rats selected according to
      their susceptibility to clonic convulsions induced by a convulsant dose 50%
      (CD50) of DMCM, a benzodiazepine inverse agonist, would differ in behavioral
      tests commonly used to measure anxiety (elevated plus-maze, open field) and
      depression (forced swimming test). In the first experiment, subgroups of adult
      male Wistar rats were selected after a single dose of DMCM and in the second
      experiment they were selected after two injections of DMCM given after an
      interval of 1 week. Those rats presenting full clonic convulsions were termed Low
      Threshold rats to DMCM-induced clonic convulsions (LTR) and those not having
      clonic convulsions High Threshold rats to DMCM-induced clonic convulsions (HTR).
      In both experiments, only those rats presenting full clonic convulsions induced
      by DMCM and those not showing any signs of motor disturbances were used in the
      behavioral tests. The results showed that the LTR subgroup selected after two
      injections of a CD50 of DMCM spent a significantly lower time in the open arms of
      the elevated plus-maze and in the off the walls area of the open field; moreover,
      this group also presented a higher number of rearings in the open field. There
      were no significant differences between HTR and LTR subgroups in the forced
      swimming test. LTR and HTR subgroups selected after only one injection of DMCM
      did not differ in the three behavioral tests. To verify if the behavioral
      differences between HTR and LTR subgroups of rats selected after two injections
      of DMCM were due to the clonic convulsion, another experiment was carried out in
      which subgroups of rats susceptible and nonsusceptible to clonic convulsions
      induced by a CD50 of picrotoxin, a GABA(A) receptor channel blocker, were
      selected and submitted to the elevated plus-maze and open field tests. The
      results obtained did not show any significant differences between these two
      subgroups in the elevated plus-maze and open field tests. In another approach to
      determine the relation between fear/anxiety and susceptibility to clonic
      convulsions, subgroups of rats were selected in the elevated plus-maze as more or
      less fearful/anxious. The CD50 for clonic convulsions induced by DMCM was
      determined for each of these two subgroups. The results showed a significantly
      lower CD50 for the more fearful/anxious subgroup, which means a higher
      susceptibility to clonic convulsions induced by DMCM. The present findings show a
      relation between susceptibility to clonic convulsions and fear/anxiety and vice
      versa which may be due to differences in the assembly of GABA(A)/allosteric
      benzodiazepine site receptors in regions of the brain.

PMID- 16297442
TI  - A randomized intervention of physical activity promotion and patient self
      monitoring in primary health care.
AB  - OBJECTIVES: To examine the effectiveness of prescription-based counseling and
      self-monitoring in the promotion of physical activity in primary health care.
      METHODS: The study was conducted in Finland during 2003-2004. Physicians from 24
      health care units (N = 67) were randomized to a prescription or a non
      prescription group. The patients (N = 265) were assigned to the groups according
      to their physician. Every other patient of the non-prescription physicians
      received a pedometer and a physical activity log (MON) and feedback about their 5
      day-recordings, the rest served as controls (CON). PA was assessed prior and 2
      and 6 months after the physician's appointment with a questionnaire. RESULTS: The
      mean increase in weekly overall physical activity at 2 months was 1.0 (95% CI 0.0
      to 2.0) session more in the prescription group than in controls. In at least
      moderate-intensity physical activity, the mean difference in changes was 0.8 (95%
      CI 0.1 to 1.5) sessions at 2 months and 0.9 (95% CI 0.2 to 1.5) sessions at 6
      months for the favor of the prescription group. Compared to controls, self
      monitoring increased the weekly duration of overall PA at 2 months on average by
      217 min (95% CI 23 to 411). CONCLUSIONS: Prescription can be recommended as a
      tool for primary health care physicians to promote physical activity. Self
      monitoring with an expert feedback can be useful in increasing especially the
      weekly duration of overall physical activity in the short term.

PMID- 16297443
TI  - Independent effect and population impact of obesity on fatal coronary heart
      disease in adults.
AB  - BACKGROUND: It is unclear whether the coronary heart disease (CHD) mortality risk
      associated with obesity is mediated only through traditional CHD risk factors.
      This analysis evaluated the independent CHD mortality risk due to obesity and
      determined its population attributable risk (PAR). METHODS: Using the NHANES I
      Epidemiologic Follow-up Study (1971-1992, n = 10,582), a diabetes-body mass index
      (BMI) variable was constructed. The hazard ratios (HR) for fatal CHD in the
      diabetes-BMI categories (adjusting for age, sex, race, exercise, education level,
      smoking, hypertension, cholesterol, and alcohol use) were determined and the PARs
      subsequently estimated. RESULTS: Compared to lean non-diabetics, the HR (95% CI)
      for fatal CHD is 0.8 (0.7, 1.1) in overweight non-diabetics, 1.4 (1.3, 2.0) in
      obese non-diabetics, 2.2 (1.2, 4.0) in lean diabetics, 2.3 (1.4, 3.9) in
      overweight diabetics, and 3.3 (1.9, 8.9) in obese diabetics. The PAR% is -6.8 (
      15.7, 1.8) in overweight non-diabetics, 6.1 (1.7, 11.1) in obese non-diabetics,
      2.0 (0.3, 4.0) in lean diabetics, 2.2 (0.6, 4.3) in overweight diabetics, and 2.2
      (0.8, 3.8) in obese diabetics. CONCLUSIONS: Obesity is an independent risk factor
      for CHD mortality even after controlling for traditional CHD risk factors. The
      PAR for CHD death in obese non-diabetics is significant. Obesity should be
      aggressively treated in those without traditional CHD risk factors.

PMID- 16297444
TI  - Hispanic acculturation and utilization of cervical cancer screening in the US.
AB  - BACKGROUND: Hispanic women have an incidence rate of invasive cervical cancer
      that is twice as high as that of non-Hispanic White women. Previous
      investigations have reported that Hispanics are less likely to utilize cancer
      screening services. Using data from the 2000 National Health Interview Survey,
      this study examined whether acculturation of Hispanic women was associated with
      cervical cancer screening. METHODS: The subjects included 2307 Hispanic women
      aged 21-70 who did not have a history of cervical cancer or a hysterectomy. Women
      were analyzed by acculturation level according to whether or not they ever had a
      Pap smear and had one in the previous year and previous 3 years. RESULTS:
      Acculturation levels tended to be inversely correlated with no Pap smear.
      Compared to lower acculturated women, women who were more acculturated were less
      likely to never had a Pap smear (OR = 0.86; 95% CI = 0.58-1.27 for moderate
      acculturated women and OR = 0.51; 95% CI = 0.29-0.89 for higher acculturated
      women). Similar results were found for having no Pap smear within the past 3
      years (OR = 0.83; 95% CI = 0.61-1.13 for moderate acculturated women and OR =
      0.73; 95% CI = 0.49-1.08 for higher acculturated women). CONCLUSION: The findings
      show that lower acculturation was associated with the under use of cervical
      cancer screening and suggest that these women might have barriers in accessing
      and utilizing Pap smears.

PMID- 16297445
TI  - Effect of roscovitine on nuclear maturation, MPF and MAP kinase activity and
      embryo development of prepubertal goat oocytes.
AB  - The low number of embryos obtained from IVM-IVF-IVC of prepubertal goat oocytes
      could be due to an incomplete cytoplasmic maturation. Roscovitine (ROS) inhibits
      MPF and MAP kinase activity and maintains the oocyte at Germinal Vesicle (GV)
      stage. The aim of this study was to determine if meiotic activity is arrested in
      prepubertal goat oocytes cultured with 0, 12.5, 25, 50 and 100 microM of ROS for
      24 h. A group of oocytes from adult goats was cultured with 25 microM of ROS to
      compare the effect of ROS on prepubertal and adult goat oocytes. A sample of
      oocytes was stained to evaluate the nuclear stage at oocyte collection time and
      after ROS incubation. IVM-oocytes not exposed to ROS formed the control group.
      Prepubertal goat IVM-oocytes were inseminated and cultured for 8 days. The
      percentage of oocytes at GV stage, after exposition to ROS was significantly
      higher in adult goat oocytes (64.5%) than in prepubertal goat oocytes. No
      differences were found among 25, 50 and 100 microM ROS concentrations (29, 23 and
      26%, oocytes at GV stage, respectively). After 8 days of culture, no differences
      in total embryos were observed between control oocytes and oocytes treated with
      12.5 and 25 microM (45.2, 36.1 and 39.4%, respectively), however the percentage
      of blastocysts was higher in the control group. Western blot for the MAPK and
      p34(cdc2) showed that both enzymes were active in prepubertal goat oocytes after
      24h of ROS exposition. In conclusion, a low percentage of prepubertal goat
      oocytes reached GV stage after ROS incubation; possibly because most of them had
      reinitiated the meiosis inside the follicle. ROS did not affect fertilization or
      total embryos but ROS showed a negative effect on blastocyst development.

PMID- 16297446
TI  - Localisation, function and composition of primary Ca(2+) spark discharge region
      in isolated smooth muscle cells from guinea-pig mesenteric arteries.
AB  - Smooth muscle cells (SMCs) contain numerous calcium release domains, grouped into
      regions discharging as a single unit. Laser scanning confocal microscopy, voltage
      clamp and immunocytochemistry of single SMCs from small mesenteric arteries of
      guinea-pig were used to study the localisation, function and macromolecular
      composition of such calcium discharge regions (CDRs). Use of the Ca(2+)-sensitive
      fluorescent dye fluo-3 or fluo-4 with BODIPY TR-X ryanodine (BTR), a fluorescent
      derivative of ryanodine, showed spontaneous Ca(2+) sparks originating from
      regions stained by BTR, located immediately under the plasma membrane, in the
      arch formed by the sarcoplasmic reticulum surrounding the nucleus. Membrane
      depolarisation or application of noradrenaline or alpha,beta-methylene ATP, a P2X
      purinoceptor agonist, elicited Ca(2+) sparks from the same, spontaneous Ca(2+)
      spark-discharging region. The most active (primary) CDR accounted for nearly 60%
      of spontaneous transient outward currents at -40 mV and these were of
      significantly higher amplitude than the ones discharged by secondary CDRs.
      Immunocytochemical staining for type 1 IP(3) receptors, BK(Ca) channels, P2X(1)
      purinoceptors or alpha(1) adrenoceptors revealed their juxtaposition with BTR
      staining at the location typical of the primary CDR. These data suggest the
      existence of a primary calcium discharge region in SMCs; its position can be
      predicted from the cell's structure, it acts as a key region for the regulation
      of membrane potential via Ca(2+) sparks and is a potential link between the
      external, neurohumoral and the cell's internal, calcium signalling system.

PMID- 16297447
TI  - Multiple interaction sites of galnon trigger its biological effects.
AB  - Galnon was first reported as a low molecular weight non-peptide agonist at
      galanin receptors [Saar et al. (2002) Proc. Natl. Acad. Sci. USA 99, 7136-7141].
      Following its systemic administration, this synthetic ligand affected a range of
      important physiological processes including appetite, seizures and pain.
      Physiological activity of galnon could not be explained solely by the activation
      of the three known galanin receptors, GalR1, GalR2 and GalR3. Consequently, it
      was possible that galnon generates its manifold effects by interacting with other
      signaling pathway components, in addition to via GalR1-3. In this report, we
      establish that galnon: (i) can penetrate across the plasma membrane of cells,
      (ii) can activate intracellular G-proteins directly independent of receptor
      activation thereby triggering downstream signaling, (iii) demonstrates
      selectivity for different G-proteins, and (iiii) is a ligand to other G-protein
      coupled receptors (GPCRs) in addition to via GalR1-3. We conclude that galnon has
      multiple sites of interaction within the GPCR signaling cascade which mediate its
      physiological effects.

PMID- 16297448
TI  - The bcl-2/IgH rearrangement in a population of 204 healthy individuals:
      occurrence, age and gender distribution, breakpoints, and detection method
      validity.
AB  - This study assessed prevalence, frequency, age and gender distribution and
      breakpoint locations, and detection method validity for the bcl-2/IgH
      rearrangement in 204 healthy individuals. For this purpose, both classic two
      step, nested, semi-quantitative PCR as well as a newly established sequence
      specific, hybridization probe-based real-time quantitative PCR (RQ-PCR) were
      employed and tested for their sensitivity and specificity for detecting t(14;18)
      positive cells in healthy blood donors. Interestingly, almost a quarter (24%;
      39/204) of all healthy individuals carried the translocation, confirming data of
      one large prior report [Summers KE, Goff LK, Wilson AG, Gupta RK, Lister TA,
      Fitzgibbon J. Frequency of the Bcl-2/IgH rearrangement in normal individuals:
      implications for the monitoring of disease in patients with follicular lymphoma.
      J Clin Oncol 2001;19(2):420-4]. Regarding presence as well as frequency of the
      translocation, no correlation to age (mean frequency 2.0:10(4), with a median of
      <l:10(4), for <40 years, and mean frequency 1.9:10(4), with a median of <l:10(4)
      for individuals>or=40 years) nor gender was detected. Comparing the two PCR
      approaches, a 95.1% concordance (194/204) regarding t(14;18) detection was
      determined for nested and RQ-PCR, with nested PCR being slightly more sensitive
      (reproducible detection limit l:10(5) cells versus 1:10(4); maximum detection
      limit l:10(6) versus 1:10(5)). Sequence analysis confirmed individual breakpoints
      for all samples analyzed (29/29), indicating detection validity for both PCR
      approaches and ruling out contamination. The breakpoint location distribution
      pattern appeared to be comparable to the pattern seen with follicular lymphoma
      (FL) patient collectives. In conclusion, clonal bcl-2/IgH rearrangements are
      indeed a very frequent observation in healthy individuals, and appear to be
      independent of age and gender in regard to presence and frequency. This
      represents a conflicting finding in context of potential biological significance,
      and presents a potential disruptive factor for minimal residual disease (MRD)
      monitoring in FL patients. Prospective future trials will have to clarify the
      biological significance of this important observation.

PMID- 16297449
TI  - Induction of high levels of protective immunity in mice after vaccination using
      dendritic cells infected with auxotrophic mutants of Mycobacterium tuberculosis.
AB  - Adoptively transferred dendritic cells presenting antigens derived from different
      pathogens have been shown to elicit specific T cell responses and to induce
      protective antibacterial immunity. We describe here the induction of high levels
      of protective immunity in mice using dendritic cells infected with auxotrophic
      mutants of Mycobacterium tuberculosis. We provide evidence that protection is
      superior to BCG and that it is associated with increased priming of CD4+ and CD8+
      T cells specific for mycobacterial antigens. This method for generating high
      levels of anti-bacterial protective immunity could be helpful in the design of
      novel vaccines against tuberculosis and other intracellular pathogens.

PMID- 16297450
TI  - Expression of gamma-aminobutyric acid B receptor subunits in hypothalamus of male
      and female developing rats.
AB  - GABA and its receptors show particular ontogenic distributions in different rat
      brain areas. Recently, GABAB receptors (GBR) have been described to assemble as
      heterodimers formed by a GBR1a/b and a GBR2 subunit. Here, the ontogeny of rat
      GBRs and the pattern of subunit expression in both sexes were determined in the
      hypothalamus, a critical area for homeostatic regulation. Male and female rats
      were sacrificed at 1, 4, 12, 20, 28, 38 days of life and at adulthood and
      hypothalami were removed and frozen. Western blots analysis for GBR1 and GBR2
      subunits showed that both were expressed in male and female hypothalamic
      membranes from day 1 to adulthood. In females, both GBR1a and GBR1b were
      maximally expressed in newborns and decreased towards adulthood. At birth,
      expression of GBR1a was significantly higher than GBR1b, while at 38 days, GBR1b
      was more abundant. In males, GBR1a and GBR1b expression was higher in young
      animals and decreased gradually showing adult levels between the second and third
      weeks of age without differences between isoforms. Comparing GBR1 variants levels
      in hypothalamus between sexes, GBR1a was significantly more abundant in females
      at birth while at 38 days its expression was higher in males; GBR1b showed no sex
      differences along development. GBR2 was detected in hypothalami of females and
      males at all ages; maximum levels were observed at 12 days and adult levels were
      attained at 38 days, without sex differences. This is the first report on the
      ontogeny of hypothalamic GABAB receptors in male and female rats, with a
      particular developmental pattern of subunit and isoform expression and presenting
      some sex differences.

PMID- 16297451
TI  - Hearing ability according to screening at conscription; comparison with earlier
      reports and with previous screening results for individuals without known ear
      disease.
AB  - OBJECTIVE: (1) To study if young, Swedish men have poorer or better hearing
      according to screening at conscription in 1988 compared to 1969-1977. (2) To
      study how the results of screening and audiometry vary across the teenage years
      for a group of boys without middle ear disease. METHOD: A birth cohort has
      earlier been well documented regarding results in four general screenings with
      follow-up and examinations and treatment for middle ear disease at the ENT
      departments in the area. Their results when screened at conscription have been
      compared with those in earlier reports on screening of Swedish conscripts. We
      have also studied results in screenings and follow-up at 11 and 14 years of age
      with special focus on small losses at the frequencies of 3, 4, 6 and 8 kHz and
      describe how 611 boys without known ear disease performed in these examinations
      and in screening at the age of 18. RESULTS: There is no obvious trend in the
      prevalence of hearing loss in Swedish conscripts. At 11 years of age 80.4% and at
      14 years of age 64.6% of small high tone losses diagnosed by screening were not
      confirmed by audiometry. Approximately half of those who had confirmed losses had
      normal screening at conscription. CONCLUSIONS: 18-year-old Swedish boys did not
      have poorer hearing in 1998 than 29 years earlier. Information drawn from
      screenings must be interpreted with caution.

PMID- 16297452
TI  - Major aorto-pulmonary collateral arteries (MAPCAs)--Bronchial fistula presenting
      as tracheotomy bleed.
AB  - Tracheal hemorrhage is a common occurrence in pediatric patients with long-term
      tracheotomies. The majority of these events are related to self-limited
      etiologies, such as granulation tissue or suction trauma. Tracheo-arterial
      fistula, however, represents a frequently fatal form of tracheal hemorrhage that
      may initially be difficult to distinguish from other causes. Previous reports
      have described the pathophysiology, presentation and management of tracheo
      arterial fistula involving the innominate artery. We describe a case of a 21
      month-old male with a history of significant congenital cardiac malformations and
      chronic tracheotomy tube dependence who presented with intermittent, brisk
      bleeding from the tracheotomy tube. He was ultimately diagnosed with and treated
      for an arterio-bronchial fistula from a major aorto-pulmonary collateral artery.
      We review the etiology and management of this disorder.

PMID- 16297453
TI  - Particularities of bacterial ecology of acute otitis media in an African
      subtropical country (Cote d'Ivoire).
AB  - BACKGROUND: Acute otitis media (AOM) is the commonest infectious disease of
      childhood. Its treatment is based on a probabilistic antibiotic therapy.
      OBJECTIVE: To determine the prevalence of different bacteria responsible for AOM
      in children in Abidjan (Cote d'Ivoire). MATERIALS AND METHODS: This is a
      prospective study, between November 2002 and August 2003. To identify bacterial
      isolates, 60 children under 15 years old with AOM were enrolled. In 52 cases, the
      sample was recovered by aspiration of a spontaneous otorrhea and in eight cases,
      it was taken by paracentesis. Nasopharyngeal swabs were cultured. Antibiotic
      susceptibility tests were performed on isolates. RESULTS: 75% of children were
      under 24 months of age. Pseudomonas aeruginosa was recovered in 31.8% of cases
      followed by Streptococcus pneumoniae (21%), Proteus (7.4%) and Staphylococcus
      (6.2%). The rate of penicillin-nonsusceptible S. pneumoniae (NSSP) was 11.8%.
      Resistance to erythromycin was 6%. For Pseudomonas, resistances to antibiotics
      were 35.5% to ceftazidim and 16% to pefloxacin, respectively, but all the strains
      were sensible to colistin, iminepem and ciprofloxacin. CONCLUSION: These data can
      modify therapeutic approaches for treatment of AOM in our country. This study
      should encourage surveillance of AOM microbiology.

PMID- 16297454
TI  - Tonsillectomy and the immune system.

PMID- 16297455
TI  - An alkaline solution simplifies nucleic acid preparation for RT-PCR and
      infectivity assays of viroids from crude sap and spotted membrane.
AB  - Formats of a simple protocol for the preparation of nucleic acids for infectivity
      and RT-PCR detection of viroids from minute amounts of plant material are
      described. The method consists of preparing crude extracts in a NaOH-EDTA
      solution and then testing the supernatant. The NaOH-EDTA extract can be used at
      four distinct stages of preparation depending upon the accuracy desired, namely:
      (1) incubation of extract for 15 min at room temperature and the use of the
      supernatant for RT-PCR; (2) the supernatant can be spotted onto a nitrocellulose
      membrane (NCM) without vacuum, and the water-eluted liquid is used for RT-PCR;
      (3) centrifugation of the extract and use of supernatant in RT-PCR; (4) for
      quantitative accuracy, spotting the centrifuged supernatant on NCM using a vacuum
      device and then using the water-eluted liquid for RT-PCR. The protocols are
      rapid, inexpensive and applicable to large-scale epidemiological survey of
      ornamental plants or crops. The membranes are easily transported long distances
      and can be stored at room temperature for several months while retaining the
      ability to detect viroids by RT-PCR and by infectivity assays.

PMID- 16297456
TI  - Recovery of Swedish Equine arteritis viruses from semen by cell culture isolation
      and RNA transfection.
AB  - Recovery of infectious Equine arteritis virus (EAV) from the semen of
      persistently infected Swedish stallions was attempted by classical cell culture
      isolation and by transfection of extracted total RNA. Whereas virus from semen
      samples stored for several months at -20 degrees C or from extended semen could
      only be recovered by transfection of extracted RNA, isolation in cell culture was
      achieved readily with fresh, unextended semen stored at -70 degrees C or directly
      used after sampling. In parallel, the viruses were examined in the variable
      region of the large glycoprotein GP5 by nested RT-PCR and direct nucleotide
      sequencing. The resulting sequences were placed into a large phylogenetic tree
      from this region, demonstrating that Swedish strains belonged to very diverse
      phylogenetic groups. This represents the first report of recovery of infectious
      EAV from archived semen samples by RNA transfection.

PMID- 16297457
TI  - A genotype 2b NS5B polymerase with novel substitutions supports replication of a
      chimeric HCV 1b:2b replicon containing a genotype 1b NS3-5A background.
AB  - HCV diversity suggests that evaluation of HCV inhibitors for broad genotypic
      efficacy is warranted. The replicon system enables cell-culture compound efficacy
      evaluation against an active replication complex, and a functional replicon
      dependent upon a genotype 2b polymerase would augment existing cell-culture
      efficacy studies that are presently limited to genotype 1a, 1b, and 2a replicons.
      We made a chimeric Neo(r) 1b:2b replicon where genotype 2b NS5B was inserted into
      a genotype 1b NS3-5A background and transfected replicon RNA to generate Neo(r)
      cell lines. All cell lines contained novel substitutions within NS5B which were
      subsequently engineered into the parental 1b:2b replicon and shown to enhance
      replication to various degrees. A single NS5B M31I substitution enhanced
      replication to levels sufficiently robust to quantify sensitivity to HCV
      inhibitors in a transient replication assay. The M31I 1b:2b replicon was
      similarly sensitive to an active-site nucleoside inhibitor of NS5B as genotype 1b
      replicons, but was insensitive to two non-nucleoside inhibitors which were
      otherwise efficacious against the genotype 1b replicons. This work describes a
      novel HCV replicon sustained by a genotype 2b polymerase that is sufficiently
      robust for quantifiable analysis in a transient replication assay, and
      demonstrates its utility in characterizing anti-HCV compounds for cross-genotypic
      efficacy.

PMID- 16297458
TI  - Call type-specific differences in vocalization-related afferents to the
      periaqueductal gray of squirrel monkeys (Saimiri sciureus).
AB  - In a recent retrograde tracing study in the squirrel monkey, we found that
      regions in the midbrain periaqueductal gray (PAG) producing different call types
      when pharmacologically stimulated, receive their input largely from the same
      structures. The aim of the present study was to find out, whether there are
      quantitative differences in this input. For this reason, we counted retrogradely
      labeled neurons in various brain regions after injections of wheatgerm agglutinin
      conjugated horseradish peroxidase (WGA-HRP) into three different vocalization
      eliciting PAG sites: one site producing non-aversive contact calls (clucking); a
      second site producing slightly aversive social mobbing calls (cackling); and a
      third site producing highly aversive defensive threat calls (shrieking). Cell
      counting was carried out by the help of the optical fractionator technique. Six
      squirrel monkeys were used, two for each call type. In some regions, marked
      differences in the number of retrogradely labeled cells between the three call
      type groups occured. Such regions are the nucl. accumbens, preoptic area,
      posterior hypothalamus, anterior cingulate cortex, subcallosal gyrus and the
      nucl. striae terminalis. In some of these regions, the number of retrogradely
      labeled cells correlated positively (posterior hypothalamus) or negatively
      (preoptic area, nucl. striae terminalis) with the "aversiveness" of the elicited
      call type. Other regions of interest, e.g., the dorsomedial prefrontal and
      precallosal cortex, amygdala and hypothalamic regions surrounding the fornix,
      revealed no clear differences in their afferent projections to the different
      vocalization-eliciting PAG sites. The results make clear that distinct
      vocalization-controlling regions in the PAG receive a qualitatively similar but
      quantitatively differentiated input.

PMID- 16297460
TI  - Cholinesterase inhibition and impacts on behavior of the Asian clam, Corbicula
      fluminea, after exposure to an organophosphate insecticide.
AB  - This study assessed the effects of exposure to an insecticide formulation
      containing the organophosphate, chlorpyrifos on cholinesterase activity,
      siphoning and burrowing ability in the Asian clam, Corbicula fluminea. Clams were
      exposed to concentrations of the pesticide ranging from 0.05 to 50 mg/L (as
      chlorpyrifos) in a series of 96-h static bioassays. Those organisms exposed to
      pesticide concentrations at or above 3.13 mg/L avoided exposure through valve
      closure during the 96-h test period, with no resultant effects on cholinesterase
      activity or behavior. Similarly, no effect was observed at low-test
      concentrations ranging from 0.05 to 0.1 mg/L, even though clams actively siphoned
      in these treatments. Asian clams exposed to the mid-range of concentrations, 0.5
      1.0 mg/L, experienced a significant reduction in cholinesterase activity and a
      reduced capacity to burrow into the substrate. While these data indicate that
      cholinesterase activity in C. fluminea could be used as a biomarker of
      organophosphorous pesticide exposure, valve closure can clearly influence
      exposure profiles and biomarker response.

PMID- 16297459
TI  - Influence of dissolved organic matter on nickel bioavailability and toxicity to
      Hyalella azteca in water-only exposures.
AB  - Dissolved organic matter (DOM) is known to reduce the bioavailability of metals
      in aquatic systems. This study evaluated the effects of DOM from various sources
      (e.g., Little Bear Lake sediment, Suwannee River, peat moss) and various DOM
      fractions (humic acids, HA; fulvic acids, FA) on the bioavailability of nickel
      (Ni) to Hyalella azteca, a common freshwater benthic invertebrate. In particular,
      this study was conducted to evaluate the effect of surficial sediment DOM on Ni
      bioavailability. Short-term (48 h) acute toxicity tests with H. azteca conducted
      in synthetic water demonstrated that the aqueous Ni concentrations required for
      lethality were greater than what could be significantly complexed by
      environmentally relevant concentrations of dissolved organic carbon (DOC: 0.6
      30.4 mg/L). At Ni concentrations sublethal to H. azteca (500 microg/L), the
      bioavailability of Ni was significantly reduced in the presence of representative
      surface water DOC concentrations regardless of DOC source or fraction. DOC
      fraction (i.e., FA and HA) differentially affected Ni speciation, but had little
      or no effect on Ni accumulation by H. azteca. Tissue Ni was found to be strongly
      dependent upon the Ni(2+) concentration in the exposure solutions and the Ni:DOC
      ratio. Overall, the concentration of DOC played a greater role than either DOC
      source or fraction in determining Ni speciation and hence bioavailability and
      toxicity to H. azteca.

PMID- 16297461
TI  - An analysis of the calcium-binding protein 1 of Fasciola gigantica with a
      comparison to its homologs in the phylum Platyhelminthes.
AB  - A full-length cDNA encoding the Fasciola gigantica calcium-binding protein 1
      (FgCaBP1) was cloned from an adult stage cDNA expression library in an
      immunoscreen using rabbit immune serum against the parasite's excretion/secretion
      antigens. The deduced amino acid sequence showed 96.3% identity to Fh22CBP of
      Fasciola hepatica. During development in the mammalian host FgCaBP1 RNA was
      detected in metacercariae, juveniles and adults and was exclusively localized to
      the tegumental cell bodies. Immune serum of a rabbit infected with F. gigantica
      detected recombinant FgCaBP1 starting from the sixth week of infection. Immune
      sera of mice infected with Schistosoma mansoni and Schistosoma mekongi cross
      reacted with recombinant FgCaBP1 in immunoblots. Recombinant FgCaBP1 showed
      calcium and magnesium-binding activity by a mobility shift during non-denaturing
      PAGE in the presence of Ca2+ or Mg2+, respectively. A polyclonal mouse anti
      rFgCaBP1 antiserum detected the native protein as a major component of the
      parasite's tegumental antigens in immunoblots and as a strictly tegumental
      antigen in tissue cross-sections of adult and juvenile parasites. Comparative
      sequence analysis of homologs from Fasciola and Schistosoma present in the
      GenBank database revealed sequence signatures specific to these trematode
      proteins and thereby indicates their origin from a single ancestor. FgCaBP1
      contains two adjacent, N-terminal located EF-hands and a C-terminal located
      domain similar to dynein light chain type 1. Independent structure predictions of
      the two domains suggest that they will fold according to the already determined
      structures of the EF-hand motif and the dynein light chain type 1 proteins.

PMID- 16297462
TI  - The VIPER elements of trypanosomes constitute a novel group of tyrosine
      recombinase-enconding retrotransposons.
AB  - VIPER was initially characterized as a 2326bp LTR-like retroelement associated to
      SIRE, a short interspersed repetitive element specific of Trypanosoma cruzi. It
      carried a single ORF that coded for a putative reverse transcriptase-RNAse H
      protein, suggesting that it could be a truncated copy of a longer retroelement.
      Herein we report the identification and characterization of a complete 4480bp
      long VIPER in the T. cruzi genome. The complete VIPER harbored three non
      overlapped domains encoding for a GAG-like, a tyrosine recombinase and a reverse
      transcriptase-RNAse H proteins. VIPER elements were also found in the genomes of
      Trypanosoma brucei and Trypanosoma vivax, but not in Leishmania sp. On the basis
      of its reverse transcriptase phylogeny, VIPER was classified as an LTR
      retroelement. However, VIPER was structurally related to the tyrosine recombinase
      encoding retroelements, DIRS and Ngaro. Phylogenetic analysis showed that VIPER's
      tyrosine recombinase grouped with the transposases RCI1 of Escherichia coli and
      Ye24 and Ye72 of Haemophilus influenzae within a major branch of prokaryotic
      recombinases. Taken together, VIPER's structure, the nature of its tyrosine
      recombinase, the unique features of its reverse transcriptase catalytic consensus
      motif and the fact that it was found in Trypanosomes, an early branching
      eukaryote, suggest that VIPER may be the closest relative of the founder element
      of the tyrosine recombinase encoding retrotransposons known up to date. Our
      analysis revealed that tyrosine recombinase-encoding retroelements were
      originated as early in evolution as non-LTR retroelements and suggests that
      VIPER, Ngaro and DIRS elements may constitute a third group of retrotransposons,
      distinct from both LTR and non-LTR retroelements.

PMID- 16297463
TI  - Mitogenic effects of both amidated and glycine-extended gastrin-releasing peptide
      in defunctioned and azoxymethane-treated rat colon in vivo.
AB  - Although there is abundant evidence that gastrin-releasing peptide acts as a
      mitogen in various carcinoma cell lines, the effect of administration of gastrin
      releasing peptide on the colorectal mucosa in vivo has not been reported. The
      aims of this study were to determine whether continuous infusion of gastrin
      releasing peptide stimulated proliferation or accelerated carcinogenesis in the
      rat gastrointestinal tract and other organs. The possible requirement for C
      terminal amidation for mitogenic activity in vivo was also investigated.
      Proliferation was measured in the colon by metaphase index and by immunostaining
      for the proliferation marker Ki-67, and in other tissues by immunostaining alone.
      Acceleration of colorectal carcinogenesis was assessed by counting aberrant crypt
      foci after treatment with the carcinogen azoxymethane. Defunctioning of the
      rectum reduced both the proliferative index and the crypt height of the rectal
      mucosa of untreated rats. Treatment with amidated or glycine-extended gastrin
      releasing peptide for 4 weeks using implanted mini-osmotic pumps resulted in a
      two- to three-fold increase in proliferation, and an increase in crypt height, in
      the defunctioned rectal mucosa (p<0.001), with smaller but significant increases
      in the caecum and distal colon. No changes in proliferation were detected in
      lung, pancreas or gastric mucosa. The numbers of aberrant crypt foci in the mid
      colon, distal colon and rectum following treatment with azoxymethane were also
      significantly increased by infusion with amidated or glycine-extended gastrin
      releasing peptide. We conclude that administration of gastrin-releasing peptide
      to mature rats stimulates proliferation and accelerates carcinogenesis in the
      colorectal mucosa, and that C-terminal amidation is not essential for either
      effect. Gastrin-releasing peptides could thus potentially act as promoters of
      colorectal carcinogenesis.

PMID- 16297464
TI  - Involvement of upstream stimulatory factor in regulation of the mouse Prnd gene
      coding for Doppel protein.
AB  - Promoter of the Prnd gene coding for the Prion-like protein Doppel contains two
      critical cis-regulatory elements, NF-Y consensus motif and canonical E-box. Here,
      we studied a role of the upstream stimulatory factor (USF) in the E-box-mediated
      activation of Prnd transcription. Co-expression of USF-1 with the luciferase
      reporter gene driven by the -185/+27 Prnd promoter fragment resulted in several
      fold increase of the luciferase activity. Conversely, mutations within the E-box
      led to a significantly reduced Prnd promoter activation. USF-1 binding was
      supported by the gel shift assay, supershift with USF-1 antibody and UV cross
      linking. The activation capacity of the related USF-2, c-Myc and HIF-2alpha
      proteins was lower compared to USF-1 suggesting that USF-1 is the major E-box
      binding transcription factor regulating the Prnd promoter.

PMID- 16297465
TI  - Identification and characterization of Spinocerebellar Ataxia Type 7 (SCA7)
      isoform SCA7b in mice.
AB  - Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease primarily
      affecting the cerebellum, brainstem and retina. The disease is caused by a
      polyglutamine expansion in ataxin-7, a protein with largely unknown function. To
      improve our knowledge of the expression and function of wild-type and expanded
      ataxin-7, we looked for alternative SCA7 transcripts in mice. We identified a
      murine SCA7 isoform (SCA7b) containing an uncharacterized exon homologous to the
      newly identified human exon 12b. Northern blot analysis revealed three exon 12b
      containing transcripts with molecular sizes of 7.5, 4.4 and 3.0 kb in mice. This
      contrasted with the situation in humans, where only one exon 12b-containing
      transcript was observed. Furthermore, Northern blot of the human 4.4 kb SCA7b
      isoform predominantly showed expression in the brain, while expression of both
      the murine 7.5-kb and the 4.4-kb transcripts were observed in several tissues
      including brain, heart, liver, kidney and testis. Quantitative real-time RT-PCR
      analysis revealed that in muscle and heart SCA7b is the predominant SCA7 isoform,
      while in brain equal levels of SCA7a and SCA7b was observed. Insertion of exon
      12b into the murine SCA7 ORF resulted in a frame-shift that gave rise to an
      alternative ataxin-7 protein (ataxin-7b). The novel 58-amino acid C-terminus in
      ataxin-7b directed the protein to a more cytoplasmic location.

PMID- 16297466
TI  - Pregnane and Xenobiotic Receptor (PXR/SXR) resides predominantly in the nuclear
      compartment of the interphase cell and associates with the condensed chromosomes
      during mitosis.
AB  - Pregnane and Xenobiotic Receptor (PXR) is a transcription factor that is
      activated by a diverse range of xenobiotics and endogenous metabolites including
      steroids, bile acids and about 50% of the prescription drugs. In specific cell
      types (e.g. liver and intestine) it serves as a 'xenosensor' by regulating
      expression of a network of genes involved in xenobiotic clearance from the body.
      PXR expression in several cancerous tissues and its regulated expression of multi
      drug resistance proteins highlight its significance in prognosis of malignancies.
      The view that subcellular localization and ligand induced movements of
      transcription factors is one of the major phenomena in regulating transcriptional
      activity, we used a green fluorescent protein tagged PXR chimera to study its
      dynamic behaviour in living cells. Under all experimental conditions, PXR was
      observed to be a predominantly nuclear protein maintaining a dynamic equilibrium
      between the nuclear and cytoplasmic compartments of the interphase cells.
      Interestingly, for the first time, a member of the nuclear receptor superfamily,
      PXR, has been observed to be associated with condensed chromosomes during all the
      mitotic stages of cell division. The significance of PXR association with mitotic
      chromosomes is discussed.

PMID- 16297467
TI  - Atrial fibrillation in patients hospitalized for congestive heart failure: the
      same prognostic influence independently of left ventricular systolic function?
AB  - Atrial fibrillation (AF) was described to be associated with an adverse prognosis
      in several studies of heart failure (HF). However, it is not clear whether it
      directly increased mortality or is only a marker for severity of HF. AIMS: To
      determine the influence of AF on mortality of HF patients distinguishing between
      patients with preserved and deteriorated systolic function (SF). METHOD AND
      RESULTS: 1636 patients who, between 1991 and 2002 had been hospitalized in a
      Cardiology Service for HF, were studied. Survival (SV) data (mean follow-up time:
      3.14 years) has shown that there was no difference in SV between patients with
      (540 patients of the whole group) and without AF in the group with preserved SF
      (presented in 38.7% of cases), however, in the group of patients with
      deteriorated SF (AF presented in 31.0% of cases), SV time was significantly
      (p=0.01) shorter among patients with AF, this association being independent of
      age, sex, aetiology, risk factors, clinical signs and pharmacological treatment;
      relative risk: 1.831(1.120-2.994). CONCLUSION: AF is more prevalent among HF
      patients with preserved SF than among those with deteriorated SF, but only
      increases the risk of death among the latter.

PMID- 16297468
TI  - An unusual combination: aortic arch coarctation associated with Dandy-Walker
      variant.
AB  - We report on a 29-year-old woman with aortic arch coarctation with cerebral
      anomalies including posterior fossa cyst, hydrocephalus, cerebellar vermis
      hypoplasia and multiple congenital anomalies including hirsutism, hipotelorism,
      shortened philtrum, unregulated teeth and short alveolar crest, rotated auricles,
      short and webbed neck, hypopigmentation on the scalp, bilateral clinodactyly,
      bilateral hallux valgus, brachydactyly on the left foot 3rd finger, hemangioma on
      the sacrum. An extra-anatomical bypass was made by grafting from the ascending to
      the distal descending aorta. Some of these features are consistent with the
      diagnosis of the other clinical syndromes except genetical expression, no
      chromosomal deletions in our patient with normal familial pedigree, however,
      cerebral anomalies are consistent with the Dandy-Walker variant. To the best of
      our knowledge, literature contains no other report of the association of aortic
      coarctation, Dandy-Walker variant with these clinical features. These previously
      undescribed combinations, however, raise the possibility of a newly recognized
      disorder.

PMID- 16297469
TI  - Treatment and outcome of biopsy-proven fulminant myocarditis in adults.
AB  - Fulminant myocarditis may be rapidly fatal with severe haemodynamic compromise in
      previously healthy patients. We reviewed our experience with eight cases of
      biopsy-proven fulminant myocarditis (seven cases with lymphocytic myocarditis and
      one with eosinophilic myocarditis). Immunosuppression was given in seven out of
      eight cases. Mechanical circulatory support was required in 50% of the patients.
      Time from onset of illness to recovery of ventricular function varied from 12 to
      17 days. All except one patient were alive at a mean follow-up of 4.4 years after
      the acute illness. Patients with acute fulminant myocarditis should be treated
      aggressively with immunosuppression and, if necessary, mechanical circulatory
      support during the first 2 to 3 weeks of the illness because of the reversible
      nature of this illness and good long-term prognosis.

PMID- 16297470
TI  - Serological evidence of altered collagen homeostasis reflects early ventricular
      remodeling following acute myocardial infarction.
AB  - BACKGROUND: Infarct expansion characterises early ventricular remodeling
      following myocardial infarction (AMI) and is a product of the balance between
      collagen degradation and synthesis. Serological markers of collagen turnover may
      help in predicting those at risk of remodeling. C-propeptide for type-I collagen
      (PICP) and C-telopeptide for type-I collagen (CITP) are markers of collagen
      synthesis and degradation, respectively. METHODS: Fifty-one patients with AMI
      were recruited and dichotomised by echocardiographic wall motion index (WMI).
      Sequential measurements of plasma PICP and CITP were correlated to this and other
      echocardiographic variables of remodeling. RESULTS: Twenty-three normal WMI, 28
      abnormal WMI. Both groups showed increases in PICP and CITP over time. However,
      mean admission CITP higher in abnormal WMI group, 4.5 vs. 3.1 ng/ml (p<0.05) as
      was peak, 6.3 vs. 4.8 ng/ml (p<0.05). Conversely, admission PICP was lower in
      abnormal WMI group 114 vs. 143 ng/ml (p<0.05). Admission CITP correlated with
      WMI, r=0.53, p<0.001. CITP>3.2 ng/ml (normal mean+2S.D.) had 74% positive
      predictive value for abnormal WMI, negative predictive value 65%. Admission CITP
      negatively correlated with mitral deceleration time (Dt), r=-0.38, p=0.01.
      CITP>3.2 was associated with lower Dt-183 vs. 221 ms, p<0.05. CONCLUSION: There
      is serological evidence of sequential increases in both collagen synthesis and
      degradation following AMI. However, the balance between these differs in patients
      who undergo remodeling, manifested by abnormal WMI and reduced Dt, compared to
      those with no evidence. They have relatively increased degradation and reduced
      synthesis, favouring net collagen breakdown. These changes occur early with
      evidence of increased breakdown on admission predicting early remodeling and
      support the role of serological markers to identify patients at risk of this.

PMID- 16297471
TI  - Progression of heart failure in right univentricular pacing compared to
      biventricular pacing.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) improves hemodynamics and
      symptoms of heart failure by reducing ventricular dyssynchronity. Conversely,
      recent studies have demonstrated that right univentricular pacing in patients
      with an ejection fraction below 40% aggravates heart failure. In this
      retrospective study, we compared progression of disease in patients with mild to
      moderate heart failure that were treated with a right univentricular pacing
      device and patients with congestive heart failure that were treated with a
      biventricular system. METHODS: 107 patients were included. 59 received a right
      ventricular pacing device and 48 a biventricular system. Patients were assessed
      after 1 and 6 months by NYHA class, echocardiographic parameters (EF, LVEDD) and
      hospitalization for heart failure. RESULTS: Hospitalization for heart failure
      after implantation of the devices was more frequent in patients that received a
      conventional pacemaker with a single lead in the right ventricle than in patients
      that were treated with a CRT system (12% vs. 6%, p<0.05), although heart failure
      was more advanced in the CRT group at baseline. Ejection fraction in the right
      ventricular pacing group further decreased from 43%+/-4 at baseline to 38%+/-4
      after 6 months (p<0.05). Left ventricular enddiastolic diameter (LVEDD) was 51+/
      7 mm and 58+/-6 mm (p<0.05) at 6 months. In the CRT group, EF was 23%+/-4 at
      baseline and 31%+/-7 after 6 months (p<0.05.). LVEDD improved from 56+/-4 mm
      before implantation to 52+/-7 mm and 6 months (p<0.05). CONCLUSION: Progression
      of heart failure symptoms in the right univentricular pacing group was more
      pronounced compared to the CRT group, despite the fact that patients assigned to
      the CRT group had more severe symptoms of heart failure at baseline.
      Biventricular pacing relieved symptoms of heart failure, whereas right
      univentricular pacing with subsequent conduction delay of the left ventricle
      further deteriorated pre-existing heart failure. Therefore, patients with an
      indication for pacemaker therapy because of bradycardia and co-existing mild to
      moderate heart failure might benefit from early implantation of a CRT system.

PMID- 16297472
TI  - Effect of a low-carbohydrate, ketogenic diet program compared to a low-fat diet
      on fasting lipoprotein subclasses.
AB  - BACKGROUND: Low-carbohydrate, ketogenic diets (LCKD) are effective for weight
      loss, but concerns remain regarding cardiovascular risk. The purpose of this
      study was to determine the effect of an LCKD program on serum lipoprotein
      subclasses. METHODS: This was a randomized, two-arm clinical trial in an
      outpatient research clinic involving overweight, hyperlipidemic community
      volunteers motivated to lose weight. Subjects were randomized to either an LCKD
      (n = 59) and nutritional supplementation (including fish, borage and flaxseed
      oil), or a low-fat, reduced-calorie diet (LFD, n = 60). The main outcomes were
      fasting serum lipoprotein subclasses determined by nuclear magnetic resonance
      analysis. RESULTS: The mean age of subjects was 44.9 years, the mean BMI was 34.4
      kg/m(2), and 76% were women. Comparing baseline to 6 months, the LCKD group had
      significant changes in large VLDL (-78%), medium VLDL (-60%), small VLDL (-57%),
      LDL particle size (+2%), large LDL (+54%), medium LDL (-42%), small LDL (-78%),
      HDL particle size (+5%), large HDL (+21%), and LDL particle concentration (-11%).
      Compared with the LFD group, the LCKD group had greater reductions in medium VLDL
      (p = 0.01), small VLDL (p = 0.01) and medium LDL (p = 0.02), and greater
      increases in VLDL particle size (p = 0.01), large LDL (p = 0.004), and HDL
      particle size (p = 0.05). CONCLUSIONS: The LCKD with nutritional supplementation
      led to beneficial changes in serum lipid subclasses during weight loss. While the
      LCKD did not lower total LDL cholesterol, it did result in a shift from small,
      dense LDL to large, buoyant LDL, which could lower cardiovascular disease risk.

PMID- 16297473
TI  - Angiotensin-II activates apoptosis, proliferation and protein synthesis in the
      left heart ventricle of newborn albino rats.
AB  - Angiotensin II (ANG-II) is a critical regulator of various signaling pathways
      involved in growth and remodeling of the vascular, cardiac, and renal cells and
      tissues. Although it contributes to several physiologic and pathologic events in
      the cardiovascular system, its role in growth and differentiation of the newborn
      heart is still unclear. We analyzed the effect of ANG-II treatment on apoptosis,
      DNA synthesis, and nucleolar organizer regions (AgNORs) activity in newborn rat
      myocardium. Injections of ANG-II for 5-days caused significant increase of the 3H
      thymidine labeling index (M+/-m) in the myocardium of 7-day-old rats (from 6.95+/
      0.32% to 8.53+/-0.22%, p<0.05). There was also significant increase in the cross
      sectional surface area of cardiomyocytes (from 686+/-57 to 872+/-54 microm2,
      p<0.05), number of nucleoli (from 2.5+/-0.05 to 2.8+/-0.1, p<0.05), and nucleolar
      surface area (from 2.6+/-0.09 to 3.2+/-0.22 microm2, p<0.05). These changes were
      accompanied by significant increase in the apoptotic indices analyzed by TDT
      mediated dUTP-biotin nick end-labeling (TUNEL) (from 0.044+/-0.01% to 0.093+/
      0.01%, p<0.05). Interestingly, we found no differences in cell proliferation
      between the test and control animals after 21-45 days of age, which were injected
      with ANG-II in the first postnatal week. However, the area of cardiomyocytes and
      the number of nucleoli in 21-day-old rats continued to increase significantly.
      Our results indicate that ANG-II modulates cardiac growth during the neonatal
      period via stimulation of apoptosis, cell cycle events and cellular growth of
      cardiomyocytes and that these effects can persist up to 15 days after injection
      of ANG-II has been completed.

PMID- 16297474
TI  - The relation between impaired glucose tolerance and slow coronary flow.
AB  - BACKGROUND: Impaired glucose tolerance is a preliminary stage in the development
      of type 2 diabetes mellitus and has been shown to increase the risk of
      cardiovascular morbidity and mortality in addition to causing endothelial
      dysfunction. In this study, we sought to determine if impaired glucose tolerance
      is related to slow coronary flow, an angiographic phenomenon caused by coronary
      micro and macrovascular endothelial dysfunction. METHODS: The population of this
      prospective study consisted of 28 patients with documented slow coronary flow,
      defined according to TIMI frame count method, [20 (71.4%) males; 51+/-9 years]
      and 30 patients with normal coronary flow [17 (56.6%) males; 47+/-6 years]. All
      study patients underwent an oral glucose tolerance test after 12 h of fasting.
      Lipid profile, hemoglobin A1c and systemic blood pressure were measured in all
      patients. RESULTS: There was no difference between two groups with respect to
      age, fasting plasma glucose, triglyceride, total cholesterol, high density
      lipoprotein, low density lipoprotein, hemoglobin A1c, systolic-diastolic blood
      pressure levels, history of smoking and alcohol consumption. Plasma glucose at 2
      h of oral glucose tolerance test was significantly higher in slow coronary flow
      patients compared to control group (145+/-44 vs. 112+/-38 mg/dl, P = 0.001,
      respectively). In addition, the number of patients who met the criteria of
      impaired glucose tolerance was significantly higher in slow coronary flow patient
      group [16 (57%) vs. 7 (23%), P = 0.002, respectively). CONCLUSIONS: Our results
      suggest that impaired glucose tolerance may be an independent etiological factor
      for slow coronary flow phenomenon.

PMID- 16297475
TI  - Bovine tuberculosis in wild boar (Sus scrofa), red deer (Cervus elaphus) and
      cattle (Bos taurus) in a Mediterranean ecosystem (1992-2004).
AB  - During the last 12 years, an increasing frequency in condemnation of hunted red
      deer and wild boar carcasses due to the presence of tubercle-like lesions has
      been observed in Extremadura (Western Spain). Before 1993, tuberculosis was a
      very rare finding in hunted animals. The current tuberculosis regional prevalence
      in cattle approaches 0.4% after years of expensive test and slaughter campaigns.
      It is imperative to investigate the epidemiology of Mycobacterium bovis infection
      in red deer and wild boar in order to keep a good health status and to maintain
      the effectiveness of domestic species TB eradication programs. The present paper
      evaluates the problem in Sierra de San Pedro, estimating the prevalence of TB in
      wild boar and red deer, the main wild artiodactyls in the area, and domestic
      cattle since 1992-2004, by the use of a low-cost surveillance method based on
      detailed pathological inspection of hunted animal carcasses. Microbiology and
      molecular epidemiology studies on several M. bovis isolates from domestic and
      wild animals helped to define the interspecies contacts. These findings, as well
      as recent history of game estates management and descriptive epidemiology field
      work, throw light on the rise and maintenance of these epizootics.

PMID- 16297476
TI  - A controlled intervention study on the effects of a very rapidly forward rotating
      shift system on sleep-wakefulness and well-being among young and elderly shift
      workers.
AB  - Shift work is related to problems in sleep/wakefulness and social life. The
      effects of a very rapidly forward rotating shift system on sleep, health and well
      being of young (-45) and elderly (45+) maintenance workers were studied by a
      controlled intervention study. In the beginning, all the workers had a continuous
      backward rotating three-shift system. A very quickly forward rotating shift
      system was developed, avoiding consecutive night shifts and with more free-time
      between the individual shifts. The effect of the new shift system on
      sleep/wakefulness and general well-being was studied by questionnaire and field
      studies including on-site registration of sleep (actigraphy), subjective
      sleepiness (KSS) and psychomotor performance (PVT). Based on a linear mixed model
      for repeated measurements, the new shift system increased the main sleep length
      after the night shift and improved alertness and PVT performance during the night
      shift among the older workers. Alertness also improved during free-time after the
      night shift and sleep complaints decreased after all shifts. The workers on the
      new shift schedule perceived the effects of the new shift system on sleep,
      alertness, general health, well-being at work, social and family life more
      positively than the workers in the old shift system. At the end of the study, all
      subjects voted for the new shift system. It is concluded that although the new
      shift system increased the operating hours at night, the very rapidly forward
      rotating shift system had positive effects on the sleep, alertness and well-being
      of especially the older shift workers.

PMID- 16297477
TI  - Down-regulation of delta-opioid receptors in Na+/H+ exchanger 1 null mutant mouse
      brain with epilepsy.
AB  - Mice lacking Na+/H+ exchanger 1 (NHE1) show a unique epilepsy phenotype although
      the underlying mechanisms remain unclear. Since expression of delta-opioid
      receptor (DOR) may be involved in control of epileptic activity, we conducted
      immunohistochemistry and autoradiography to investigate whether DOR expression is
      dys-regulated in the brain of NHE1 null mouse. Immunohistochemistry showed a
      decline in DOR expression in hippocampus and cortex. Autoradiographic results
      confirmed that the density of DOR was decreased in most cortical and hippocampal
      regions such as striate and temporal cortex, hippocampal CA1 and CA3 regions
      (reduced by 27.7 +/- 6.4%, 29.4 +/- 5.1%, 40.7 +/- 4.4% and 20.6 +/- 5.7%,
      respectively, P < 0.05). These data demonstrate that NHE1 null mutation leads to
      a reduction of DOR expression in the cortical and hippocampal regions, which
      provides a new clue for the genesis of epilepsy.

PMID- 16297478
TI  - Molecular, technological and safety characterization of Gram-positive catalase
      positive cocci from slightly fermented sausages.
AB  - The population of Gram-positive catalase-positive cocci from slightly fermented
      sausages was characterized at species and strain level by molecular techniques
      and some technological and hygienic aspects were also considered. Staphylococcus
      xylosus was the predominant species (80.8%) followed by Staphylococcus warneri
      (8.3%), Staphylococcus epidermidis (5.8%) Staphylococcus carnosus (4.6%), and
      Kocuria varians (0.4%). Proteolytic activity was observed in 23% of the isolates.
      The species with the highest percentage of proteolytic strains was S. warneri.
      Lipolytic activity was found in 45.8% of the isolates and S. xylosus was the
      species with the highest percentage of lipolytic isolates. Biogenic amine
      production was not widely distributed (only 14.6% of the isolates). Tyramine was
      the most intense amine produced, although by only 4.6% of the isolates.
      Phenylethylamine was more frequently detected (10.8% of isolates) but at lower
      levels. Some strains also produced putrescine (3.3%), cadaverine (2.9%),
      histamine (1.3%) and tryptamine (0.4%). All isolates were susceptible to
      linezolid and vancomicin and over 70% were resistant to penicillin G, ampicillin
      and sulphonamides. Most of the mecA+ strains (only 4.6% of isolates) also
      displayed resistance to multiple antibiotics. A reduced enterotoxigenic potential
      was found. Only 3.3% of isolates showed staphylococcal enterotoxins genes, all
      identified as entC gene. The combination of RAPD-PCR and plasmid profiling
      allowed the discrimination of 208 different profiles among the 240 Gram-positive
      catalase-positive cocci characterized, indicating a great genetic variability.

PMID- 16297479
TI  - Amino acid profiles of lactic acid bacteria, isolated from kefir grains and kefir
      starter made from them.
AB  - The characteristics of cell growth, lactic acid production, amino acid release
      and consumption by single-strain cultures of lactic acid bacteria (isolated from
      kefir grains), and by a multiple-strain kefir starter prepared from them, were
      studied. The change in the levels of free amino acids was followed throughout the
      kefir process: single-strain kefir bacteria and the kefir starter (Lactococcus
      lactis C15-1%+Lactobacillus helveticus MP12-3%+(Streptococcus thermophilus
      T15+Lactobacillus bulgaricus HP1 = 1:1)-3%) were cultivated in pasteurized (92
      degrees C for 20 min) cow's milk (3% fat content) at 28 degrees C for 5 h (the
      kefir starter reached pH 4.7) and subsequently grown at 20 degrees C for 16 h;
      storage was at 4 degrees C for 168 h. The strain L. helveticus MP12 was unrivaled
      with respect to free amino acid production (53.38 mg (100 g)(-1)) and cell growth
      (17.8 x 10(8) CFU ml(-1)); however, it manifested the lowest acidification
      activity. L. bulgaricus HP1 released approximately 3.7 times less amino acids,
      nearly 5 times lower cell growth, and produced about 1.2 times more lactic acid.
      S. thermophilus T15 demonstrated dramatically complex amino acid necessities for
      growth and metabolism. With L. lactis C15, the highest levels of growth and
      lactic acid synthesis were recorded (18.3 x 10(8) CFU ml(-1) and 7.8 g l(-1)
      lactic acid at the 21st hour), and as for free amino acid production, it
      approximated L. bulgaricus HP1 (17.03 mg (100 g)(-1) maximum concentration). In
      the L. lactis C15 culture, the amino acids were used more actively throughout the
      first exponential growth phase (by the 10th hour) than during the second growth
      phase. The unique properties of the L. helveticus MP12 strain to produce amino
      acids were employed to create a symbiotic bioconsortium kefir culture, which,
      under conditions of kefir formation, enhanced lactic acid production and
      shortened the time required to reach pH 4.7; intensified cell growth activity,
      resulting in a respective 90- and 60-fold increase in the concentration of
      lactobacilli and cocci in the mixed culture compared to individual cultures; and
      accumulated free amino acids in the final kefir with higher total concentrations
      (56.88 mg (100 g)(-1)) and an individual concentration of essential amino acids
      (1.5 times) greater than that of yogurt.

PMID- 16297480
TI  - A novel approach for calculating shelf life of minimally processed vegetables.
AB  - Shelf life of minimally processed vegetables is often calculated by using the
      kinetic parameters of Gompertz equation as modified by Zwietering et al.
      [Zwietering, M.H., Jongenburger, F.M., Roumbouts, M., van't Riet, K., 1990.
      Modelling of the bacterial growth curve. Applied and Environmental Microbiology
      56, 1875-1881.] taking 5x10(7) CFU/g as the maximum acceptable contamination
      value consistent with acceptable quality of these products. As this method does
      not allow estimation of the standard errors of the shelf life, in this paper the
      modified Gompertz equation was re-parameterized to directly include the shelf
      life as a fitting parameter among the Gompertz parameters. Being the shelf life a
      fitting parameter is possible to determine its confidence interval by fitting the
      proposed equation to the experimental data. The goodness-of-fit of this new
      equation was tested by using mesophilic bacteria cell loads from different
      minimally processed vegetables (packaged fresh-cut lettuce, fennel and shredded
      carrots) that differed for some process operations or for package atmosphere. The
      new equation was able to describe the data well and to estimate the shelf life.
      The results obtained emphasize the importance of using the standard errors for
      the shelf life value to show significant differences among the samples.

PMID- 16297482
TI  - Paclitaxel poliglumex (XYOTAX, CT-2103): a macromolecular taxane.
AB  - Paclitaxel poliglumex (PPX) is an innovative macromolecular taxane designed to
      increase the therapeutic index of paclitaxel. This large macromolecular conjugate
      of paclitaxel and poly-L-glutamic acid accumulates in tumor tissues by taking
      advantage of the enhanced permeability of tumor vasculature and lack of lymphatic
      drainage. Preclinical studies in animal tumor models demonstrate that PPX is more
      effective than standard paclitaxel and is associated with prolonged tumor
      exposure to active drug while minimizing systemic exposure. Phase 1 and 2
      clinical studies with PPX showed encouraging outcomes compared to standard
      taxanes with reduced neutropenia and alopecia and allowed a more convenient
      administration schedule without the need for routine premedications. Human
      pharmacokinetic data are consistent with prolonged tumor exposure to active drug
      and a limited systemic exposure. Three phase 3 trials in nonsmall cell lung
      cancer (STELLAR 2, 3, and 4) have completed enrollment and results are expected
      in 2005.

PMID- 16297483
TI  - A new self-emulsifying formulation of itraconazole with improved dissolution and
      oral absorption.
AB  - To enhance the dissolution and oral absorption of poorly water-soluble
      itraconazole, self-emulsifying drug delivery system (SEDDS) composed of oil,
      surfactant and cosurfactant for oral administration of itraconazole was
      formulated, and its physicochemical properties and pharmacokinetic parameters of
      itraconazole were evaluated. Among the surfactants and oils studied, Transcutol,
      Pluronic L64 and tocopherol acetate were chosen that showed the maximal
      solubility to itraconazole. The solubility of itraconazole was further improved
      by the addition of hydrochloric acid. Droplet size of itraconazole emulsion was
      kept constant both in simulated gastric fluid without pepsin (pH 1.2) and
      simulated intestinal fluid (pH 6.8) throughout 120-min incubation period.
      Itraconazole in the SEDDS rapidly dissolved in every dissolution medium whereas
      the Sporanox showed different dissolution patterns during the 120-min incubation
      according to the dissolution media. In fasted and fed normal diet group, AUC(0-
      >24 h) and the mean maximum plasma level (Cmax) of itraconazole after oral
      administration of SEDDS in rats were comparable to those of itraconazole after
      oral dose of Sporanox. However, in fed lipidic diet group, AUC and Cmax after
      oral administration of SEDDS in rats were 3.7- and 2.8-fold higher, respectively,
      compared with those of Sporanox. These results demonstrate that the SEDDS of
      itraconazole composed of Transcutol, Pluronic L64 and tocopherol acetate greatly
      enhanced the bioavailability of itraconazole after the dose, particularly not
      influenced by food intake or not. Thus, this system may provide a useful dosage
      form for oral water-insoluble drug without food effect.

PMID- 16297484
TI  - Structural variation of cationic lipids: minimum requirement for improved
      oligonucleotide delivery into cells.
AB  - In vivo transfection efficiency (TE) using cationic liposome/oligonucleotide
      (ODN) complexes is often hampered by interactions with serum components. Novel
      cationic lipids with different hydroxyethyl or dihydroxypropyl ammonium
      backbones, esterified hydrocarbon chains and hydroxy substituents have been
      synthesized and applied in cationic liposome formulations with and without the
      helper lipid DOPE (1:1, m/m). Their properties for cellular ODN delivery were
      determined using fluorescently labeled ODNs (F-ODNs). Cationic lipids with
      hydrocarbon chains esterified to non-glycerol backbones in non-vicinal
      configuration were completely ineffective in nuclear ODN-delivery. Instead, an
      increased cytoplasmic localization of F-ODNs was observed. Cationic lipids
      equipped with only one hydrocarbon were completely incompetent for cellular ODN
      delivery. In the absence of serum, all cationic lipids tested with hydrocarbon
      chains in vicinal configuration esterified to a glycerol backbone (the respective
      N-(1,2-diacyl-dihydroxypropyl)-N,N,N-trimethyl-ammoniumchlorides or N-(1,2-diacyl
      dihydroxypropyl)-N(hydroxyethyl)-N,N-dimethyl-ammoniumchlorides as well as N-(1,2
      diacyl-dihydroxypropyl)-N(1,2-dihydroxypropyl)-N,N-dimethyl-ammoniumchlorides
      with lauroyl, myristoyl, palmitoyl, stearoyl and erucoyl chains) were able to
      transfect cells when combined with DOPE (20-80% nuclear fluorescence).
      Remarkably, only the analog esterified with two myristoyl chains was equally
      effective even in the absence of DOPE. By adding hydroxy groups to the N-alkyl
      residue, TE under serum conditions was improved yielding transfection rates of
      55%, 75% and 90% for 0, 1 or 2 substituted hydroxy groups, respectively. For
      plasmid DNA, different requirements were identified. Again, the analog with two
      myristoyl chains was most effective but only in the presence of DOPE. However,
      the addition of hydroxy groups had no influence on the TE in the presence of
      serum.

PMID- 16297481
TI  - Sequences of avian reovirus M1, M2 and M3 genes and predicted structure/function
      of the encoded mu proteins.
AB  - We report the first sequence analysis of the entire complement of M-class genome
      segments of an avian reovirus (ARV). We analyzed the M1, M2 and M3 genome segment
      sequences, and sequences of the corresponding muA, muB and muNS proteins, of two
      virus strains, ARV138 and ARV176. The ARV M1 genes were 2,283 nucleotides in
      length and predicted to encode muA proteins of 732 residues. Alignment of the
      homologous mammalian reovirus (MRV) mu2 and ARV muA proteins revealed a
      relatively low overall amino acid identity ( approximately 30%), although several
      highly conserved regions were identified that may contribute to conserved
      structural and/or functional properties of this minor core protein (i.e. the MRV
      mu2 protein is an NTPase and a putative RNA-dependent RNA polymerase cofactor).
      The ARV M2 genes were 2158 nucleotides in length, encoding predicted muB major
      outer capsid proteins of 676 amino acids, more than 30 amino acids shorter than
      the homologous MRV mu1 proteins. In spite of the difference in size, the ARV/MRV
      muB/mu1 proteins were more conserved than any of the homologous proteins encoded
      by other M- or S-class genome segments, exhibiting percent amino acid identities
      of approximately 45%. The conserved regions included the residues involved in the
      maturation- and entry- specific proteolytic cleavages that occur in the MRV mu1
      protein. Notably missing was a region recently implicated in MRV mu1
      stabilization and in forming "hub and spokes" complexes in the MRV outer capsid.
      The ARV M3 genes were 1996 nucleotides in length and predicted to encode a muNS
      non-structural protein of 635 amino acids, significantly shorter than the
      homologous MRV muNS protein, which is attributed to several substantial deletions
      in the aligned ARV muNS proteins. Alignments of the ARV and MRV muNS proteins
      revealed a low overall amino acid identity ( approximately 25%), although several
      regions were relatively conserved.

PMID- 16297485
TI  - Freeze-drying of cationic polymer DNA complexes enables their long-term storage
      and reverse transfection of post-mitotic cells.
AB  - WERI-Rb1 retinoblastoma (Rb) cell line, a human photoreceptor model, is
      notoriously difficult to transfect. Culturing of the WERI-Rb1 cells as a
      monolayer is complicated and cells are easily detached during transfection.
      Furthermore, transfection efficiencies in monolayer and in suspension are
      moderate at best which has limited the analysis of photoreceptor-specific
      promoters with low activity. To overcome these limitations, we developed a
      straightforward reverse transfection method for WERI-Rb1 cells wherein snap
      frozen DNA/polyethylenimine complexes are freeze-dried on the surface of 48-well
      plates and stored in desiccator until cells are seeded for transfection.
      Comparing to conventional transfection, reverse transfection turned out to have
      equal or better transfection efficiency. In addition, while conventional
      transfection with cationic polymers requires serum-free conditions, reverse
      transfection can be performed in the presence of serum. Importantly,
      DNA/polyethylenimine complexes promote cell adhesion to the plates. This enables
      cell culturing as monolayers with concurrent complex uptake. Also, long-term
      storage of the plates did not reduce the transfection efficiency nor it had any
      effects on the cell toxicity. Because of the stability of complexes, reverse
      transfection enables large-scale transfection of hard-to-transfect retinoblastoma
      cells thus providing a reproducible, cost-effective and versatile tool for
      parallel screening of proteins and gene regulatory elements used in diverse
      applications.

PMID- 16297486
TI  - Triggered release of proteins from emulsan-alginate beads.
AB  - Emulsan/alginate beads were studied for protein adsorption and stability in the
      context of controlled release. The beads, 400 +/- 80 microm diameter with
      approximately 10% emulsan content, offer unusual opportunities for delivery of
      proteins due to the natural ability of emulsan to bind proteins, coupled with the
      selective biological activation features of this complex
      lipoheteropolysaccharide. The binding capacity of azo-bovine serum albumin by the
      emulsan/alginate beads was 0.637 +/- 0.004 vs. 0.170 +/- 0.007 microg/mg for
      beads formed from alginate alone. In additional protein adsorption experiments,
      the lipase and subtilisin maintained activity when adsorbed to the
      emulsan/alginate beads albeit with lower specific activity when compared to the
      enzyme free in solution. However, the half life of the adsorbed enzyme was
      significantly higher than the free forms. To explore functional utility of this
      system, two types of triggered release were studied in the context of these bead
      systems. First, azo-BSA as a model protein was physically bound to
      emulsan/alginate beads and then selectively released by triggering with
      subtilisin, a serine protease, which cleaves the azo dye, sulfanilic acid, from
      the bound protein. In absence of subtilisin no triggered release was observed.
      Second, azo-BSA as a prodrug model, was adsorbed to the emulsan/alginate beads
      and then release of the dye was demonstrated by lipase treatment which cleaves
      the fatty acid esters from the emulsan structure to release the bound protein.
      The results establish the versatility and utility of emulsan-based beads for
      protein binding and triggered release.

PMID- 16297488
TI  - Randomised controlled trial evaluating lifestyle interventions in people with
      impaired glucose tolerance.
AB  - AIM: To evaluate the effectiveness of lifestyle interventions in people with
      impaired glucose tolerance (IGT). METHODS: Participants with IGT (n=78),
      diagnosed on two consecutive oral glucose tolerance tests (OGTTs), were randomly
      assigned to a 2-year lifestyle intervention or to a control group. Main outcome
      measures were changes from baseline in: nutrient intake; physical activity;
      anthropometry, glucose tolerance and insulin sensitivity. Measurements were
      repeated at 6, 12 and 24 months follow-up. RESULTS: After 24 months follow-up,
      there was a significant fall in total fat consumption (difference in change
      between groups (Delta intervention-Delta control)= -17.9, 95% confidence interval
      (CI) -33.6 to -2.1g/day) as a result of the intervention. Body mass was
      significantly lower in the intervention group compared with controls after 6
      months (-1.6, 95% CI -2.9 to -0.4 kg) and 24 months (-3.3, 95% CI -5.7 to -0.89
      kg). Whole body insulin sensitivity, assessed by the short insulin tolerance test
      (ITT), improved after 12 months in the intervention group (0.52, 95% CI 0.15
      0.89%/min). CONCLUSIONS: These findings complement the findings of the Finnish
      Diabetes Prevention Study and the American Diabetes Prevention Study, both of
      which tested intensive interventions, by showing that pragmatic lifestyle
      interventions result in improvements in obesity and whole body insulin
      sensitivity in individuals with IGT, without change in other cardiovascular risk
      factors.

PMID- 16297487
TI  - Lipid nanoparticles for skin penetration enhancement-correlation to drug
      localization within the particle matrix as determined by fluorescence and
      parelectric spectroscopy.
AB  - With topical treatment of skin diseases, the requirement of a high and
      reproducible drug uptake often still is not met. Moreover, drug targeting to
      specific skin strata may improve the use of agents which are prone to cause local
      unwanted effects. Recent investigations have indicated that improved uptake and
      skin targeting may become feasible by means of nanoparticular systems such as
      solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and
      nanoemulsions (NE). Here we describe techniques to characterize drug loading to
      carrier systems and skin penetration profiles by using the lipophilic dye nile
      red as a model agent. Since the mode of drug association with the particle matrix
      may strongly influence the efficiency of skin targeting, parelectric spectroscopy
      (PS) was used to differentiate between matrix incorporation and attachment to the
      particle surface and fluorescence spectroscopy (FS) to solve dye distribution
      within NLC particles. Nile red was incorporated into the lipid matrix or the
      covering tensed shell, respectively, of SLN and NLC with all the lipids studied
      (Compritol, Precirol, oleic acid, Miglyol). In NLC, the dye was enriched in the
      liquid phase. Next, nile red concentrations were followed by image analysis of
      vertical sections of pigskin treated with dye-loaded nanoparticular dispersions
      and an oil-in-water cream for 4 and 8 h in vitro. Following the SLN dispersions,
      dye penetration increased about fourfold over the uptake obtained following the
      cream. NLC turned out less potent (<threefold increase) and penetration appeared
      even reduced when applying a NE. In contrast to previous studies with
      glucocorticoids attached to the surface of SLN, a targeting effect was not
      detected here. Therefore, drug targeting appears to be more strictly related to
      the mode of interaction of drug and particle than penetration enhancement.

PMID- 16297489
TI  - Detection of ketonemia and its relationship with hyperglycemia in type 1 diabetic
      patients.
AB  - The aims of this study were to assess the prevalence of ketosis in type 1
      diabetic patients with casual hyperglycemia (>250 mg/dl), to establish the
      relationship between glycemia and ketonemia during daily life, and to determine
      the utility of ketonemia. Capillary glycemia levels from 562 type 1 diabetic
      patients were recorded. Prevalence of casual hyperglycemia was 27.58%, and
      prevalence of asymptomatic ketonemia was 8.39%. Regarding blood ketone levels,
      110 out of 155 patients (70.96%) had blood ketone levels of between 0 and 0.1
      mmol/l and 32 out of 155 patients (20.63%) had blood ketone levels of between 0.2
      and 0.4 mmol/l. Surprisingly, the mean glycemia levels in these subgroups did not
      differ and was consistently high (around 300 mg/dl), leading to the observation
      that even ketone levels considered as non-pathologic should probably be taken
      into account for a proper diabetes control. Some discrepancies between
      quantitative determination of ketonuria and qualitative determination of
      ketonemia were observed. That is in 20 patients with positive ketonuria,
      ketonemia was not detected, probably because ketosis was already resolved.
      Asymptomatic ketosis was observed in the hyperglycemic type 1 diabetic
      population, and metabolic control of these patients with a point of care device
      is recommended, together with a subsequent revision of insulin treatment.
      Furthermore, this study supports the opinion that the presence of ketosis,
      detected by beta-OHB levels, even below levels considered as pathologic, together
      with hyperglycemia, must be taken into account for proper monitoring and
      therapeutic control of diabetic patients.

PMID- 16297490
TI  - "Will all liver transplantation patients eventually die from cancer?".

PMID- 16297492
TI  - Hepatocellular carcinoma in the United States. Lessons from a population-based
      study in Medicare recipients.

PMID- 16297493
TI  - Nitric oxide and portal hypertension: interface of vasoreactivity and
      angiogenesis.

PMID- 16297494
TI  - Why are some medical specialists working part-time, while others work full-time?
AB  - Although medical specialists primarily work full-time, part-time work is on the
      increase, a trend that can be found worldwide. This article seeks to answer the
      question why some medical specialists work part-time, while others do not
      although they are willing to work part-time. Two approaches are used. First, we
      studied reported reasons and as a second approach we used a theoretical model,
      based on goal-directed behavior and restrictions. A questionnaire was sent to all
      internists (N=817), surgeons (N=693) and radiologists (N=621) working in general
      hospitals in The Netherlands. Questions were asked about personal traits,
      characteristics of the work situation, and motives for working full-time or part
      time. Frequencies were reported for the reasons given, and multilevel analysis
      was used to test the theoretical model. The results show that the reported
      reasons for working part-time and being willing to work part-time are the same:
      the importance of family and leisure pursuits. The second approach showed that
      medical specialists working part-time tend to be female, older, and have children
      below the age of five. Surgeons are least likely to work part-time. A willingness
      to work part-time is purely individual and not related to any of the explanatory
      variables. We conclude that working part-time is related to both professional and
      personal circumstances. Policy should be aimed at removing the organizational
      difficulties that obstruct the realization of part-time work. Alternatively,
      perhaps there should be a change in working hours for all medical specialists. As
      the majority of all full-time working medical specialists are willing to work
      part-time, this might indicate that most medical specialists actually prefer
      "normal" working hours.

PMID- 16297495
TI  - Response to "Use of cervical cancer screening among insured women: the extent of
      missed opportunities" [Health Policy 73 (2005) 194-201].

PMID- 16297496
TI  - Adenoviral interneuronal transportation after retrograde gene transfer in mice.
AB  - Although retrograde gene transfer from infected muscles to neurons by viral
      vectors has been known for years, it is still unknown whether interneuronal gene
      transportation of viral vectors occurs after retrograde gene transfer. To
      determine this, we injected adenoviral vectors carrying eGFP gene with or without
      a neural tracer into the right gastrocnemius muscles of mice. After 7 days, some
      spinal motor neurons were detected with green fluorescence but without the signal
      of neural tracer. In addition, nerves with green fluorescence could be noted in
      the right lumbosacral paraspinal muscles of viral-injected mice. The green
      fluorescence in the right lumbosacral paraspinal muscles might have resulted from
      retrograde gene transportation from the viral-injected gastrocnemius muscles to
      the spinal neurons, followed by interneuronal transfer and anterograde expression
      of eGFP in the axons belonging to neurons innervating the paraspinal muscles.
      This phenomenon of interneuronal transportation raises the possibility that we
      could treat motoneuron diseases by injection of viral vectors containing
      therapeutic genes into a few muscles resulting in widespread beneficial effects.

PMID- 16297497
TI  - Dendrimer biocompatibility and toxicity.
AB  - The field of biomedical dendrimers is still in its infancy, but the explosion of
      interest in dendrimers and dendronised polymers as inherently active therapeutic
      agents, as vectors for targeted delivery of drugs, peptides and oligonucleotides,
      and as permeability enhancers able to promote oral and transdermal drug delivery
      makes it timely to review current knowledge regarding the toxicology of these
      dendrimer chemistries (currently under development for biomedical applications).
      Clinical experience with polymeric excipients, plasma expanders, and most
      recently the development of more 'classical polymer'-derived therapeutics can be
      used to guide development of "safe" dendritic polymers. Moreover, in future it
      will only ever be possible to designate a dendrimer as "safe" when related to a
      specific application. The so far limited clinical experience using dendrimers
      make it impossible to designate any particular chemistry intrinsically "safe" or
      "toxic". Although there is widespread concern as to the safety of nano-sized
      particles, preclinical and clinical experience gained during the development of
      polymeric excipients, biomedical polymers and polymer therapeutics shows that
      judicious development of dendrimer chemistry for each specific application will
      ensure development of safe and important materials for biomedical and
      pharmaceutical use.

PMID- 16297498
TI  - Legal and ethical status of stem cells as medicinal products.
AB  - The realisation of the full potential of products based on stem cells in a
      clinical setting demands robust scientific evidence, underpinned by legitimate
      regulatory requirements to ensure their safety and efficacy. This review examines
      the legal aspects of the use of stem cells in the laboratory and in the
      development of new therapies and pharmaceutical products. UK and European legal
      and regulatory documents and directives are used as the framework for discussion
      of the current status and future prospects.

PMID- 16297499
TI  - Estimation of prognostic value of Bcl-xL gene expression in non-small cell lung
      cancer.
AB  - The aim of our study was to estimate the expression of the Bcl-xL gene, a member
      of Bcl-2 family, in NSCLC patients. A total of 60 consecutive patients diagnosed
      with NSCLC that underwent chemotherapy prior to surgery were reviewed. Bcl-xL
      expression was assessed on paraffin sections by in situ hybridization (ISH) and
      immunohistochemistry (IMH). We observed the presence of mRNA of Bcl-xL gene and
      its protein product overexpression in most patients (60 and 81.7%, respectively).
      In material examined no significant correlation was observed between the pattern
      of Bcl-xL or protein expression and any clinicopathological factors evaluated.
      The expression of Bcl-xL protein was low (less than 10% positive cells) in 11
      patients (median survival time 29 months) as compared to 49 patients with
      overexpression (median survival time 21.0 months). The difference was not of
      statistic significance (p=0.27). In examined group the Bcl-xL mRNA was found in
      36 patients, while it was absent in 24 cases. Median survival time was 14.5 and
      86.5 months, respectively (p=0.001). In addition, 19.4% of 5-year survivals were
      achieved in patients with overexpression and 54.2% in patients with no mRNA
      present (p=0.002). The percentage of 5-year survival in patients with protein
      expression assessed by IMH was 30.6% (p=0.31). The estimation of Bcl-xL
      expression on mRNA and protein level was compared by the means of sign test and
      the significant difference was found (p=0.009). The inconsistency was related to
      35% of cases. In comparison with IMH, ISH technique appeared to be more specific
      and accurate in assessment of 5-year survival (25 and 65%; 65 and 70%,
      respectively). The results of our study indicate that Bcl-xL mRNA overexpression
      may suggest poor prognosis in NSCLC.

PMID- 16297500
TI  - Effects on hunger and satiety, perceived portion size and pleasantness of taste
      of varying the portion size of foods: a brief review of selected studies.
AB  - The portion size of foods has been identified as an important environmental
      factor known to affect short-term energy intake. Experiments that were conducted
      both in the free-living environment and in laboratory-based settings to
      investigate the effects of portion size on energy intake unanimously showed that
      as the portion size of food increased, so did subjects' energy intake. Despite
      the fact that the profound effects of portion size on energy intake are well
      documented, the mechanisms by which portion size affects energy intake are poorly
      understood. There is some evidence that sensory influences (e.g. visual and
      olfactory cues), cognitive factors (e.g. learning, social norms, monetary
      considerations), and post-ingestive consequences (e.g. sensations of hunger and
      fullness) related to the portion size of foods may interact to affect the amount
      of food that is consumed during a meal.

PMID- 16297501
TI  - Stimulatory effect of n-octanoylated ghrelin on locomotor activity in the
      goldfish, Carassius auratus.
AB  - Ghrelin is implicated in growth and feeding regulation in fish. The influence of
      ghrelin on behavior has not been well studied and the physiological role of des
      fatty acid modification of this peptide is unclear. Therefore, the effects of
      intracerebroventricular (ICV) and intraperitoneal (IP) administration of
      synthetic n-octanoylated (acyl) goldfish ghrelin and des-n-octanoylated (des
      acyl) ghrelin on locomotor and orexigenic activity in the goldfish were examined.
      ICV administration of acyl ghrelin at doses of 1 and 2 pmol/g body weight (BW)
      and IP administration at 16 pmol/g BW both induced significant increases in
      locomotor activity during for 45-60 min after treatment. Cumulative food intake
      was significantly increased by ICV injection of acyl ghrelin at doses of 1 and 2
      pmol/g BW and IP injection at 8 and 16 pmol/g BW during the 60-min post-treatment
      observation period. In contrast, ICV and IP administration of des-acyl ghrelin
      produced no changes in locomotor and orexigenic activity. We also analyzed
      fasting-induced changes in the expression of ghrelin mRNA in the brain and
      intestine using a real-time PCR method. The level of ghrelin mRNA in the
      intestine, but not in the brain, obtained from fish fasted for 7 days was
      significantly higher than that in fish that had been fed normally. These results
      suggest that, in the goldfish, acyl ghrelin, but not des-acyl ghrelin, stimulates
      locomotor activity and enhances food intake via central and peripheral pathways.

PMID- 16297503
TI  - [A rare diagnosis: a case report of an isolated pulmonary valve endocarditis].

PMID- 16297502
TI  - A biologically active hydrophobic T-1-conotoxin from the venom of Conus spurius.
AB  - A major, very hydrophobic peptide, sr5a, was purified from the venom duct of
      Conus spurius specimens collected in the Yucatan Channel, Mexico. Its amino acid
      sequence (IINWCCLIFYQCC; calculated monoisotopic mass assuming two disulfide
      bridges 1616.68 Da) was determined by automatic Edman degradation after reduction
      and alkylation, and confirmed by mass spectrometry (ESI monoisotopic mass,
      1616.60; MALDI monoisotopic mass 1616.42 Da). The primary structure of sr5a
      showed the pattern that characterizes the family of the T-1-conotoxins, which
      belong to the T-superfamily of conotoxins. The disulfide bonds were determined by
      partial reduction and alkylation with N-ethylmaleimide, followed by total
      reduction and alkylation with 4-vinylpyridine, and automatic Edman sequencing.
      The connectivity of the Cys residues (I-III, II-IV) is the same as that found in
      the T-1-conotoxin family. When injected intracranially (2.0 nmol) into mice,
      peptide sr5a caused depressed behavioral activity.

PMID- 16297504
TI  - Hormone levels in children during the first week of ICU-admission: is there an
      effect of adequate feeding?
AB  - BACKGROUND & AIMS: To evaluate the course of hormonal parameters in relation to
      clinical parameters, illness severity and nutritional intake in children admitted
      to the pediatric ICU during the first week of admission. METHODS: Prospective,
      observational study. Levels of triiodothyronine (T3), reverse T3 (rT3), ratio
      T3/rT3 and insulin-like growth factor I (IGF-1) were evaluated in 84 critically
      ill children (50 term neonates and 34 children aged 32 d-15 yr) admitted to our
      multidisciplinary tertiary pediatric intensive care unit within 24 h after
      admission, on days 4 and 6 after admission. Changes in hormones levels over time
      were related to illness severity, C-reactive protein-levels and the adequacy of
      feeding. RESULTS: For both age groups IGF-1 levels remained low until day 4, but
      at day 6 IGF-1 levels were significantly higher than admission level. In 88% and
      89% of the older children, T3 levels remained below normal at days 4 and 6,
      respectively. In both age groups, rT3 levels declined significantly over time,
      whereas the ratio T3/rT3 increased. The increases in IGF-1, T3 and ratio T3/rT3
      and decrease in rT3 were significantly associated with decreases in CRP-levels.
      No significant relations were found between changes in IGF-1 and thyroid hormone
      levels during admission and the adequacy of energy and protein intake.
      CONCLUSIONS: During the first week of ICU-admission, abnormalities in levels of
      IGF-1, T3 and rT3 were frequently observed in critically ill children, especially
      in the children aged >1 month. The adequacy of feeding did not seem to affect the
      normalization of IGF-1 and thyroid hormone levels.

PMID- 16297505
TI  - Protective effect of red wine on oxidative stress and antioxidant enzyme
      activities in the brain and kidney induced by feeding high cholesterol in rats.
AB  - The effect of red wine (400 ml/70 kg) on brain and kidney oxidative stress and
      antioxidative enzymes activities induced by cholesterol-enriched diet
      (supplemented with 1.65% of cholesterol (w/w) for 4 weeks) was studied in rats.
      When red wine (Montilla-Moriles, Cordoba, Spain) was simultaneously supplemented
      to high-cholesterol diet for 4 weeks, total cholesterol and lipid peroxidation
      products in the brain, kidney and erythrocytes significantly decreased compared
      with the high-cholesterol, while GSH content and antioxidative enzymes activities
      enhanced. On the other hand, the urinary excretion of urea, creatinine and
      albumin decreased significantly. These results suggest that red wine may have a
      neuro-nephroprotective effect against oxidative stress and hypercholesterolemia.

PMID- 16297506
TI  - Treatment with supplementary arginine, vitamin C and zinc in patients with
      pressure ulcers: a randomised controlled trial.
AB  - BACKGROUND & AIMS: Nutrients putatively implicated in pressure ulcer healing were
      evaluated in a clinical setting. METHODS: Sixteen inpatients with a stage 2, 3 or
      4 pressure ulcer randomised to receive daily a standard hospital diet; a standard
      diet plus two high-protein/energy supplements; or a standard diet plus two high
      protein/energy supplements containing additional arginine (9 g), vitamin C (500
      mg) and zinc (30 mg). Nutritional status measurements (dietary, anthropometric
      and biochemical) and pressure ulcer size and severity (by PUSH tool; Pressure
      Ulcer Scale for Healing; 0=completely healed, 17=greatest severity) were measured
      weekly for 3 weeks. RESULTS: Patients' age and BMI ranges were 37-92 years and
      16.4-28.1 k g/m2) respectively. Baseline PUSH scores were similar between groups
      (8.7+/-0.5). Only patients receiving additional arginine, vitamin C and zinc
      demonstrated a clinically significant improvement in pressure ulcer healing
      (9.4+/-1.2 vs. 2.6+/-0.6; baseline and week 3, respectively; P<0.01). All patient
      groups presented with low serum albumin and zinc and elevated C-reactive protein.
      There were no significant changes in biochemical markers, oral dietary intake or
      weight in any group. CONCLUSIONS: In this small set of patients, supplementary
      arginine, vitamin C and zinc significantly improved the rate of pressure ulcer
      healing. The results need to be confirmed in a larger study.

PMID- 16297507
TI  - Response to pneumococcal vaccine in chronic obstructive lung disease--the effect
      of ongoing, systemic steroid treatment.
AB  - Forty-nine patients with chronic obstructive lung disease (COPD) were block
      randomized in four groups to investigate, if different degrees of steroid-load
      influenced the effect of pneumococcal-vaccination on antibody level and clinical
      variables during 6 months of follow-up. The groups included 13 patients without
      systemic steroids for the previous 3 months, all vaccinated at entrance in the
      study and treated with steroids for 4 weeks. Nine patients had chronic steroid
      treatment both before and during the investigation; they were vaccinated at the
      entrance in the study. Fifteen patients without systemic steroids for the
      previous 3 months were vaccinated after the end of a 4-week steroid treatment.
      Twelve patients served as controls, and were not vaccinated. Totally, 60%-78% of
      vaccinated patients in the three groups had a rise in antibody level, and a later
      decrease compared to two of the 12 control patients (p<0.01). This difference was
      also significant (p<0.05) for the patients vaccinated at entrance in the
      hospital. No differences were observed among the clinical variables: pneumonia,
      exacerbations, admittance to hospital, increase in the use of steroids or beta
      agonists, and the use of antibiotics. We conclude that a rise in antibody level
      after pneumococcal vaccination can be expected in patients with COPD despite of
      the use of systemic steroids. The clinical effect of vaccination is debatable.

PMID- 16297511
TI  - A key factor in the identification of metallic foreign bodies in head and neck
      trauma.

PMID- 16297510
TI  - Two community hepatitis B outbreaks: an argument for vaccinating incarcerated
      persons.
AB  - Current recommendations have not resulted in routine vaccination of correctional
      facility inmates for hepatitis B. We investigated two hepatitis B outbreaks.
      Outbreak 1 involved 4 cases epidemiologically linked to persons who had been in
      jail. Outbreak 2 involved 48 community cases; 69% had a history of incarceration.
      Two-thirds of the cases in these outbreaks might have been prevented by a program
      of routine vaccination of local jail inmates. Priority should be given to
      developing and supporting practical programs to vaccinate the high-risk
      populations in correctional facilities against hepatitis B.

PMID- 16297512
TI  - An exploratory study of loading and morphometric factors associated with specific
      failure modes in fatigue testing of lumbar motion segments.
AB  - BACKGROUND: There is currently little information regarding factors associated
      with specific modes of motion segment failure using a fatigue failure model.
      METHODS: Thirty-six human lumbar motion segments were fatigue tested using spinal
      compressive and shear loads that simulated lifting a 9 kg weight in three torso
      flexion angles (0 degrees, 22.5 degrees, and 45 degrees). Twenty-five segments
      failed via fatigue prior to the 10,000 cycle maximum. These specimens were
      visually inspected and dissected so that the mode(s) of failure could be
      determined. Failure modes included endplate fractures (classified into nine
      varieties), vertebral body fractures, and/or zygapophysial joint disruption.
      Logistic regression analyses were performed to determine whether certain
      morphometric variables, amount of motion segment flexion, disk degeneration
      scores, and/or loading characteristics were associated with the occurrence of
      specific failure modes. FINDINGS: Results indicated that stellate endplate
      fractures were associated with increased posterior shear forces (P < 0.05) and
      less degenerated discs (P < 0.01). Fractures running laterally across the
      endplate were associated with motion segments having larger volumes (P < 0.01).
      Endplate depression was more common in smaller specimens (P < 0.01), as well as
      those experiencing increased posterior shear force (P < 0.05). Zygapophysial
      joint damage was more likely to occur in a neutral posture (P < 0.01).
      INTERPRETATION: These results suggest that prediction of failure modes (e.g.,
      specific endplate fracture patterns) may be possible (at least for older
      specimens) given knowledge of the spinal loads along with certain characteristics
      of the lumbar spine.

PMID- 16297513
TI  - Effects of metals on condition and reproductive output of the smooth toadfish in
      Sydney estuaries, south-eastern Australia.
AB  - This study determined the condition and reproductive output of a common estuarine
      toadfish, Tetractenos glaber, in two metal contaminated and two reference
      estuaries near Sydney, Australia. Female toadfish from metal contaminated
      estuaries were smaller and younger than in reference estuaries; however, it could
      not be resolved whether these differences were due to direct effects of metal
      contamination or differences in nutritional value of prey. Lipid content in liver
      and gonad tissues was inversely related with levels of As, Pb, Cd and Co in
      sediment. In contrast, protein content in liver, gonad and muscle tissues was
      positively related to sediment levels of Ni and Co. Increased levels of Pb in
      gonads were associated with decreased oocyte diameter and density. This suggests
      a reduction in egg size and fecundity, which ultimately may lead to a decline in
      female reproductive output. Changes in fish health and reproduction caused by
      chemical pollutants may alter fish population and community structure.

PMID- 16297509
TI  - Long-term egg-yolk adaptation of the Orientia tsutsugamushi for preparation of a
      formalinized immunogen.
AB  - To assess the feasibility of preparing a killed rickettsial vaccine against the
      scrub typhus, the Karp and Gilliam strains of the Orientia tsutsugamushi were
      adapted through sequential passages in eggs for more than 100 times over 9 years
      to produce approximately five times more antigen than the unadapted rickettsia.
      The egg-grown rickettsia was purified by differential centrifugation and batch
      type ion-exchange chromatography, and inactivated by formalin treatment. Strong
      protective immunity was acquired against lethal challenges of the homologous
      strains and lasted fully for longer than 8 months in the C3H/He mice immunized
      with either of the single-strain immunogen or in combination of the two strain
      immuinogens. However, neither immunogen protected animals from the challenges
      with the two heterologous strains or Boryong, the prevalent strain in Korea,
      despite that three antigenic proteins of 47, 56, and 110 kDa were eminent in both
      preparations. IgM, IgG, and neutralizing antibody were induced in the immunized
      mice in a level and pattern comparable to that in animals infected with live
      rickettsiae.

PMID- 16297515
TI  - Effects of oil sands tailings compounds and harsh weather on mortality rates,
      growth and detoxification efforts in nestling tree swallows (Tachycineta
      bicolor).
AB  - Oil sands mining companies in Alberta, Canada, are evaluating the feasibility of
      using wetlands to detoxify oil sands process material (OSPM) as a reclamation
      strategy. Reproductive success, nestling growth, survival and ethoxyresorufin-o
      deethylase (EROD) activity were measured in tree swallows (Tachycineta bicolor)
      on experimental wetlands. In 2003, harsh weather triggered a widespread nestling
      die-off. Mortality rates on the control site reached 48% while they ranged from
      59% to 100% on reclaimed wetlands. The odds of dying on the most process-affected
      sites were more than ten times higher than those on the control site. In 2004,
      weather was less challenging. Mortality rates were low, but nestlings on
      reclaimed wetlands weighed less than those on the control site, and had higher
      EROD activity. These results indicate that compared with reference birds,
      nestlings from OSPM-impacted wetlands may be less able to withstand additional
      stressors, which could decrease their chances of survival after fledging.

PMID- 16297514
TI  - Sorption and bioreduction of hexavalent uranium at a military facility by the
      Chesapeake Bay.
AB  - Directly adjacent to the Chesapeake Bay lies the Aberdeen Proving Ground, a U.S.
      Army facility where testing of armor-piercing ammunitions has resulted in the
      deposition of >70,000 kg of depleted uranium (DU) to local soils and sediments.
      Results of previous environmental monitoring suggested limited mobilization in
      the impact area and no transport of DU into the nation's largest estuary. To
      determine if physical and biological reactions constitute mechanisms involved in
      limiting contaminant transport, the sorption and biotransformation behavior of
      the radionuclide was studied using geochemical modeling and laboratory microcosms
      (500 ppb U(VI) initially). An immediate decline in dissolved U(VI) concentrations
      was observed under both sterile and non-sterile conditions due to rapid
      association of U(VI) with natural organic matter in the sediment. Reduction of
      U(VI) to U(IV) occurred only in non-sterile microcosms. In the non-sterile
      samples, intrinsic bioreduction of uranium involved bacteria of the order
      Clostridiales and was only moderately enhanced by the addition of acetate (41%
      vs. 56% in 121 days). Overall, this study demonstrates that the migration of
      depleted uranium from the APG site into the Chesapeake Bay may be limited by a
      combination of processes that include rapid sorption of U(VI) species to natural
      organic matter, followed by slow, intrinsic bioreduction to U(IV).

PMID- 16297517
TI  - Urban environmental geochemistry of trace metals.
AB  - As the world's urban population continues to grow, it becomes increasingly
      imperative to understand the dynamic interactions between human activities and
      the urban environment. The development of urban environmental geochemistry has
      yielded a significant volume of scientific information about geochemical
      phenomena found uniquely in the urban environment, such as the distribution,
      dispersion, and geochemical characteristics of some toxic and potentially toxic
      trace metals. The aim of this paper is to provide an overview of the development
      of urban environmental geochemistry as a field of scientific study and highlight
      major transitions during the course of its development from its establishment to
      the major scientific interests in the field today. An extensive literature review
      is also conducted of trace metal contamination of the urban terrestrial
      environment, in particular of urban soils, in which the uniqueness of the urban
      environment and its influences on trace metal contamination are elaborated.
      Potential areas of future development in urban environmental geochemistry are
      identified and discussed.

PMID- 16297516
TI  - California sea lions (Zalophus californianus californianus) have lower
      chlorinated hydrocarbon contents in northern Baja California, Mexico, than in
      California, USA.
AB  - Chlorinated hydrocarbons (CHs) were determined in blubber samples of 18
      California sea lions (Zalophus californianus californianus) that stranded dead
      along Todos Santos Bay, Ensenada, Baja California, Mexico, January 2000-November
      2001. Summation operatorDDTs were the dominant group (geometric mean 3.8 microg/g
      lipid weight), followed by polychlorinated biphenyls ( summation operatorPCBs,
      2.96 microg/g), chlordanes (0.12 microg/g) and hexachlorocyclohexanes (0.06
      microg/g). The summation operatorDDTs/ summation operatorPCBs ratio was 1.3. We
      found CH levels more than one order of magnitude lower than those reported for
      California sea lion samples collected along the California coast, USA, during the
      same period as our study. This sharp north-south gradient suggests that Z.
      californianus stranded in Ensenada (most of them males) would probably have
      foraged during the summer near rookeries 500-1000 km south of Ensenada and the
      rest of the year migrate northwards, foraging along the Baja California
      peninsula, including Ensenada, and probably farther north.

PMID- 16297518
TI  - Price elasticity of demand for malt liquor beer: findings from a US pilot study.
AB  - Our objective is to estimate the relative price elasticity of demand for malt
      liquor beer (MLB), regular beer, hard liquor, and a combined group of all other
      alcoholic beverages. Three hundred and twenty-nine alcohol consumers (mostly
      male) in South-Central Los Angeles answered a series of questions pertaining to
      expected consumption responses to hypothetical price increases. We found that
      based on a 10% price increase, the mean price elasticity of demand (% change in
      quantity demanded / % change in price) was -0.79 for MLB drinkers, -1.14 for
      regular beer drinkers, -1.11 for hard liquor drinkers, and -1.69 for the combined
      group of all other drinkers. Logistic regression analysis revealed that the
      personal characteristics significantly related to being a MLB drinker were older
      age, not working, being homeless, and a daily drinker. Daily (or nearly daily)
      drinkers were more likely to be married, earning lower incomes, and hard liquor
      drinkers. This study is the first to investigate the price elasticity of demand
      for MLB drinkers and other heavy alcohol consumers in poor urban neighborhoods of
      the US. Future research can use the methods from this pilot study to more
      rigorously examine and compare the price sensitivity among heavy drinking groups.

PMID- 16297519
TI  - Effects of polysaccharide peptide (PSP) from Coriolus versicolor on the
      pharmacokinetics of cyclophosphamide in the rat and cytotoxicity in HepG2 cells.
AB  - Polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, has been
      shown to restore the immunological effects against cyclophosphamide-induced
      immuno-suppression, although the mechanism(s) involved remain uncertain. This
      study investigated the PSP-cyclophosphamide interaction by studying the effects
      of PSP on the pharmacokinetic of cyclophosphamide in the rat and the effect of
      PSP on the cytotoxic effects of cyclophosphamide on a cancer cell line (HepG2
      cells). In the pharmacokinetic studies in the rat, acute pre-treatment of PSP (4
      micromol/kg/day, i.p.) decreased the clearance (CL) of cyclophosphamide by 31%,
      with a concomitant increase in the area under concentration-time curve (AUC) by
      44%, and prolongation of the plasma half-life (T(1/2)) by 43%. Sub-chronic pre
      treatment of PSP (2 micromol/kg/day, i.p., 3 days) decreased the CL of
      cyclophosphamide by 33%, with a concomitant increase in the AUC by 50%, and
      prolongation of the plasma T(1/2) by 34%. In cytotoxicity studies using HepG2
      cells, non-toxic dose of PSP (1-10 microM) enhanced the cytotoxicity of
      cyclophosphamide. PSP at 10 microM further decreased HepG2 cell viability by 22%
      compared to when cyclophosphamide was present alone. In summary, PSP enhanced the
      cytotoxic effect of cyclophosphamide on a cancer cell line in vitro and altered
      the pharmacokinetics of cyclophosphamide in vivo in the rat. Both of these
      effects may be beneficial in the use of PSP as an adjunct to cyclophosphamide
      treatment.

PMID- 16297520
TI  - The in vitro effects of quinupristin/dalfopristin, erythromycin and levofloxacin
      at low concentrations on the expression of different cell adhesion molecules on
      the surface of endothelial cells (Eahy926).
AB  - OBJECTIVES: Infusion phlebitis is a common clinical problem associated with some
      antimicrobial agents. The pathomechanism of infusion phlebitis has not yet been
      elucidated, however, it has been proposed that chemical irritation of the
      endothelium leads to subsequent sterile inflammation with recruitment and
      migration of leukocytes. In the present study, cultured endothelial cells were
      exposed to antibiotics at clinically relevant concentrations to detect changes in
      various cell surface markers. METHODS: Cells from the endothelial hybrid cell
      line Eahy926 were exposed to quinupristin/dalfopristin, erythromycin and
      levofloxacin at increasing concentrations (3, 10, 30 and 100 mg/l) for 24 h.
      After washing, the cells were marked with monoclonal antibodies against different
      cell surface antigens (intercellular cell adhesion molecule-1 [ICAM-1], platelet
      endothelial cell adhesion molecule-1 [PECAM-1], vascular cell adhesion molecule-1
      [VCAM-1], E-selectin, L-selectin, CD34, alpha(2), alpha(5), beta(1) and beta(4)
      integrin chains and analysed by flow cytometry. For comparison, cells were either
      untreated or incubated with tumor necrosis factor alpha (TNF-alpha) at a
      concentration of 10 ng/ml and analysed for ICAM-1, VCAM-1 and E-selectin
      expression. RESULTS: There was an increase in ICAM-1 expression on endothelial
      cells with increasing concentrations of quinupristin/dalfopristin. VCAM-1, E
      selectin, L-selectin and CD34 showed an excursive upregulation at the
      concentration of 100 mg/l only, while no consistent changes were observed for
      PECAM-1 and the integrins. Markedly less prominent changes in the expression of
      these adhesion molecules were seen with erythromycin while no relevant changes at
      all occurred with levofloxacin. The absolute change in ICAM-1 activation with
      quinupristin/dalfopristin at 100 mg/l (34.4%) was less pronounced than that
      observed after stimulation with TNF-alpha (>80%). CONCLUSIONS: The results of
      this study indicate that antibiotics with a high potential for local cytotoxicity
      may cause an inflammatory response by endothelial cells even at rather low
      concentrations. The increase in expression of cell surface markers involved in
      cell-cell interaction could be an important mechanism in the development of
      infusion phlebitis.

PMID- 16297521
TI  - Acute cadmium intoxication induces alpha-class glutathione S-transferase protein
      synthesis and enzyme activity in rat liver.
AB  - Acute cadmium intoxication affects glutathione S-transferase (GST) in rat liver.
      It has been found that 24h after i.p. cadmium administration to rats, at a dose
      of 2.5 mg CdCl(2)kg(-1) body weight, the activity of this enzyme in liver cytosol
      increased by 40%. A less stimulatory effect persisted till 48 h and thereafter
      the enzyme activity normalized. Since, GST isoenzymes belong to different classes
      in mammalian tissues, we used quantitative immunoassays to verify which family of
      GST isoenzymes is influenced by this intoxication. Only alpha-class glutathione S
      transferase (alpha-GST) proteins were detected in rat liver cytosol and their
      level increased by about 25%, 24h after cadmium treatment. No pi-GST isoforms
      were found in liver cytosol from either normal or cadmium-treated rats. Co
      administration of actinomycin D with cadmium normalized both the protein level
      and the activity of alpha-GST, suggesting that some effect occurs on enzyme
      transcription of these isoenzymes by this metal. On the other hand, it seems
      unlikely that the stimulatory effect is due to the high level of peroxides caused
      by lipid peroxidation, since Vitamin E administration strongly reduced the TBARS
      level, but did not cause any GST activity decrease.

PMID- 16297508
TI  - Development of nonhuman adenoviruses as vaccine vectors.
AB  - Human adenoviral (HAd) vectors have demonstrated great potential as vaccine
      vectors. Preclinical and clinical studies have demonstrated the feasibility of
      vector design, robust antigen expression and protective immunity using this
      system. However, clinical use of adenoviral vectors for vaccine purposes is
      anticipated to be limited by vector immunity that is either preexisting or
      develops rapidly following the first inoculation with adenoviral vectors. Vector
      immunity inactivates the vector particles and rapidly removes the transduced
      cells, thereby limiting the duration of transgene expression. Due to strong
      vector immunity, subsequent use of the same vector is usually less efficient. In
      order to circumvent this limitation, nonhuman adenoviral vectors have been
      proposed as alternative vectors. In addition to eluding HAd immunity, these
      vectors possess most of the attractive features of HAd vectors. Several
      replication-competent or replication-defective nonhuman adenoviral vectors have
      been developed and investigated for their potential as vaccine-delivery vectors.
      Here, we review recent advances in the design and characterization of various
      nonhuman adenoviral vectors, and discuss their potential applications for human
      and animal vaccination.

PMID- 16297522
TI  - Studies on the goitrogenic mechanism of action of N,N,N',N'-tetramethylthiourea.
AB  - N,N,N',N'-Tetramethylthiourea (TMTU) is a rat goitrogen inducing thyroid
      hyperplasia, hypertrophy, and tumor formation. Little is known about the exact
      underlying mechanism of action. As thyroid peroxidase (TPO) and type I
      iodothyronine deiodinase (ID-I) have been established as targets of goitrogenic
      thiourea derivatives, we investigated interactions of TMTU with target enzymes
      using a partially purified fraction from hog thyroids or solubilized hog thyroid
      microsomes and 10,000g supernatant from rat liver homogenate, respectively, as
      enzyme sources. For comparison, comprehensively characterized goitrogenic
      thiourea derivatives were studied as well. In contrast to propylthiouracil (PTU),
      and like ethylenethiourea (ETU), TMTU only marginally affected TPO-catalyzed
      oxidation of guaiacol. TMTU, like ETU, concentration-dependently suppressed TPO
      catalyzed iodine formation with concomitant oxidative metabolism. Suppression
      ceased upon consumption of thiourea derivatives, the rate of the reappearing
      iodine formation was similar to that of controls. TMTU, like ETU, also suppressed
      non-enzymatic and TPO-catalyzed monoiodination of l-tyrosine with a stoichiometry
      of 2:1, i.e., one molecule of thiourea derivative suppressed two times
      monoiodination. TMTU and ETU were unable to irreversibly inhibit TPO. In contrast
      to PTU, TMTU did not inhibit ID-I. These findings provide evidence that TMTU
      interferes with thyroid hormone synthesis at the level of iodination and
      demonstrate a metabolic route for the oxidative detoxification of TMTU in the
      thyroid suggesting that low-level or intermittent exposure to TMTU would have
      only minimal effects on thyroid hormone synthesis. Finally, it can be concluded
      that meaningful toxicological studies on TPO inhibition can be performed without
      a need for highly purified TPO.

PMID- 16297523
TI  - Active compression-decompression CPR necessitates follow-up post mortem.

PMID- 16297524
TI  - The p75 neurotrophin receptor in human development and disease.
AB  - The functional effects of nerve growth factor (NGF) and its precursor, pro-NGF,
      are thought to be mediated through binding of these ligands to one or both of
      their receptors, TrkA and p75NTR. While the signaling pathways and downstream
      effects of NGF binding to TrkA are reasonably well known, those related to the
      binding of NGF and pro-NGF to p75NTR are less well understood. Furthermore,
      p75NTR appears to play functional roles that are unrelated to its ability to bind
      NGF and pro-NGF, some of which are ligand-independent and others of which are
      dependent upon binding to other neurotrophins. As these functional roles and
      their biochemical mechanisms become better known, the importance of p75NTR,
      related receptors, and both extracellular ligands and intracellular interactors
      and effectors for human development and health has become increasingly apparent.
      A complete understanding of p75NTR and its cellular partners is best served by
      approaching the remaining questions from both sides, with studies of function in
      normal states and studies of dysfunction in aberrant states mutually informing
      one another.

PMID- 16297525
TI  - The relationship between headache and preeclampsia.

PMID- 16297526
TI  - Use of fluorescence to monitor the incorporation of horseradish peroxidase into a
      sol-gel derived medium.
AB  - The solvatochromic dye nile red has been employed to monitor the incorporation of
      an enzyme (horseradish peroxidase) into a sol-gel derived medium. The
      fluorescence spectrum of the dye, when incorporated into the enzyme, was analysed
      as the sum of Gaussian component spectra and relative changes between these
      component spectra were monitored upon encapsulation of the dye-enzyme system
      within the host matrix. Activity of the confined enzyme was verified and the
      effect of temperature was also investigated, through the examination of nile red
      fluorescence in the sol-gel derived matrix, where a stabilising effect was noted.

PMID- 16297527
TI  - Functions of alpha 2 macroglobulins in pregnancy.
AB  - The alpha 2 macroglobulins (A2M) are a family of abundant plasma proteins
      produced predominantly by the mammalian liver. Pregnancy zone proteins (PZP) of
      humans and rats are A2M family members that bind a wide variety of macromolecules
      including the important pregnancy-associated molecules such as vascular
      endothelial growth factor, placenta growth factor and glycodelin (also called
      PP14). Recently, a mouse gene analogous to PZP (A2M of pregnancy or A2Mp) was
      cloned. A2Mp has a unique pattern of expression in reproductive and
      cardiovascular tissues and, unexpectedly, is not expressed by liver. Since
      changes in heart function and remodeling of renal and uterine vasculature are
      amongst the earliest maternal responses to pregnancy, the product of the A2Mp
      gene has been postulated to systemically regulate these changes. A2Ms with and
      without non-covalently bound ligands also down regulate immune cell activation
      but promote immune cell migration, additional features associated with
      gestational success. Here, we review the A2M gene families of mice and humans,
      the predicted structural relationships between A2M and its pregnancy induced
      forms and the postulated roles for this gene family in normal pregnancy.

PMID- 16297528
TI  - Incessant ovulation, inflammation and epithelial ovarian carcinogenesis:
      revisiting old hypotheses.
AB  - Epithelial ovarian cancer (EOC) is often a lethal disease because in many cases
      early symptoms go undetected. Although research proceeds apace, as yet there are
      few reliable and specific biomarkers for the early stages of the disease. EOC is
      an umbrella label for a highly heterogeneous collection of cancers, which
      includes tumours of low malignant potential, serous cystadenomas, mucinous and
      clear cell carcinomas, all of which are likely to arise from a number of
      epithelial cell types and a variety of progenitor lesions. Many, but not all
      types of EOC are thought to arise from the cells lining ovarian inclusion cysts.
      In this review, we discuss the hypotheses that have driven our ideas on
      epithelial ovarian carcinogenesis and examine the morphological and genetic
      evidence for pathways to EOC. The emergence of laser-capture microdissection and
      expression profiling by microarray technologies offers the promise of defining
      these pathways more accurately, as well as providing us with the tools for
      earlier diagnosis.

PMID- 16297529
TI  - Estrogen regulation of the scavenger receptor class B gene: Anti-atherogenic or
      steroidogenic, is there a priority?
AB  - High density lipoprotein (HDL) participates in reverse cholesterol transport and
      in the delivery of cholesterol to the liver and steroidogenic tissues by a
      mechanism called "selective lipid uptake" which is mediated by the HDL receptor,
      scavenger receptor B type I (SR-BI). Overexpression of SR-BI suppresses
      atherosclerosis by increasing reverse cholesterol transport. In contrast, genetic
      ablation of SR-BI has a negative effect on cardiovascular physiology in both
      males and females and a gender specific negative impact on female fertility.
      Cholesterol is essential for mammalian embryonic development as a necessary
      component of cell membranes and as a substrate for steroidogenesis. The SR-BI
      receptor is highly expressed in the human placenta allowing the growing fetus to
      obtain a considerable portion of cholesterol from maternal lipoproteins.
      Estrogen, which plays an important role in maintaining pregnancy, has been shown
      to enhance plasma HDL levels and promote reverse cholesterol transport. Since SR
      BI is the major determinant of serum HDL levels, direct regulation of the SR-BI
      gene by estrogen is theorized. The objective of this manuscript is to summarize
      the current information related to estrogen regulation of the gene that codes for
      the SR-BI receptor.

PMID- 16297530
TI  - Laterality does not influence early mortality in MCA ischemic stroke.
AB  - OBJECTIVES: There is clinical and experimental evidence involving the insula in
      the control of the autonomic system and cardiac function, with differential
      participation of right and left brain hemispheres, and these differences could
      influence mortality in the acute phase of brain hemisphere ischemic infarcts.
      METHODS: We have analyzed retrospectively the mortality during initial
      hospitalization in a series of 504 consecutive, unselected patients with middle
      cerebral artery (MCA) ischemic infarcts to detect potential differences between
      right (220 patients) and left (284 patients) lesions. RESULTS: Factors associated
      with a higher mortality were the infarct size, the occurrence of nosocomial
      respiratory infection, age and a history of diabetes mellitus or chronic
      obstructive pulmonary disease. CONCLUSIONS: The laterality of the infarct did not
      have a significant influence on stroke mortality during the admission period for
      the acute stage.

PMID- 16297532
TI  - Role of copper transporters in the uptake and efflux of platinum containing
      drugs.
AB  - Cellular mechanisms for the uptake, intracellular distribution and efflux of the
      platinum (Pt) containing compounds cisplatin (DDP), carboplatin (CBDCA) and
      oxaliplatin (LOHP) are unknown. Current data suggest that specialized
      transporters/carriers mediate the transport of Pt drugs across the cellular
      membranes. Specific roles for the copper (Cu) transporters CTR1, ATP7A and ATP7B
      have been demonstrated during recent years. The finding that in cultured cells
      and tumor samples a correlation can be found between the expression of Cu
      transporters and the degree of the acquired resistance to Pt drug suggests that
      the Cu transporters are important constituents of the program that regulates
      sensitivity to Pt drugs. A model is presented that describes the function of Cu
      transporters in the regulation of Pt drug uptake and efflux.

PMID- 16297533
TI  - A simple method to assess detonation temperature without using any experimental
      data and computer code.
AB  - Detonation temperature of C(a)H(b)N(c)O(d) explosives can be predicted from a, b,
      c, d and calculated gas phase heat of formation of explosives without using any
      assumed detonation products and experimental data. Two new correlations are
      introduced for calculation of detonation temperature of aromatic and non-aromatic
      explosive compounds so that it is shown here how simply calculated heat of
      formation by additivity rule and atomic composition are only necessary data for
      this simple prediction. Calculated detonation temperatures by the introduced
      correlations for both pure and explosive formulations show good agreement with
      respect to measured detonation temperatures and complicated computer codes. The
      average mean absolute error in detonation temperature is within about 7.0%.

PMID- 16297535
TI  - Carbonyl compounds in the roadside environment of Hong Kong.
AB  - The levels of carbonyl compounds were determined at the roadside urban station at
      the Hong Kong Polytechnic University (HKPU) campus during January 2002 to
      February 2002. Nine carbonyl compounds were quantified in this study. Temperature
      and solar radiation were found to affect the photochemical reactions of the
      carbonyls. Formaldehyde/acetaldehyde ratio ranged from 1.27 to 1.35. Strong
      correlations between formaldehyde and acetaldehyde were found, in the time period
      1800-2100, which indicated that they were originated from the same sources during
      this time period. Roadside carbonyl samples were also collected at four other
      roadside environments during 2001. Kwai Chung (KC) station showed the highest
      average formaldehyde and acetaldehyde concentrations due to its highest traffic
      flow, especially for diesel vehicles. High concentration of toluene emitted from
      gasoline-fueled vehicles was believed to be the cause of high benzaldehyde level
      at the Central (CT) station through the photochemical oxidation of toluene. The
      average concentrations of formaldehyde and acetaldehyde in Hong Kong are well
      within the ranges reported in roadside environments of other urban cities.
      However, Mexico City in Mexico and Cairo in Egypt had much higher concentration
      levels of formaldehyde and acetaldehyde than in Hong Kong roadside environment
      due to the incomplete combustion of different fuel compositions.

PMID- 16297534
TI  - Effects of road runoff on biomass and metabolic activity of periphyton in
      experimental streams.
AB  - Aquatic ecosystems could be enriched with inorganic and organic matters after
      road runoff discharge. In this context, we studied the effects of road runoff on
      river biofilms (periphyton). To operate under controlled conditions the
      experiments were carried out in two indoor experimental streams. Glass slides
      were used as artificial substrates for the periphyton colonisation in the
      experimental streams. Current velocity was maintained at 12 cms(-1) (slow) in the
      first experimental stream and at 50 cms(-1) (fast) in the second one. The
      periphyton communities were periodically exposed to road runoff over 30 days. For
      this experiment, the road runoff was collected in settling basins of a motorway
      during rainfall events. The runoff was then characterised according to physical
      and chemical parameters. We tested two exposure durations (1 and 4 h) and two
      runoff dilutions (10% and 50%). Two laboratory experiments carried out during
      this study revealed that the biomass (AFDW: 0.92-2.83 g m(-2)), the chlorophyll a
      content (6.8-78.9 mg m(-2)) and the metabolic activity (net primary production:
      61-334 m gO(2) m(-2)h(-1) and respiration: 17.2-68.3 mg O(2) m(-2) h(-1)) of the
      biofilms increased (p < 0.05). However, this was a function of current velocity,
      the runoff exposure duration, and the content in organic and inorganic elements
      present in the tested rainwater. Experimental streams constituted a simplified
      natural system, which did not allow the reproduction of all the environmental
      conditions. Thus, these experiments should be performed on natural sites.

PMID- 16297536
TI  - Photocatalytic degradation of methylene blue in TiO2 aqueous suspensions using
      microwave powered electrodeless discharge lamps.
AB  - Photocatalytic degradation of methylene blue (MB) in TiO(2) aqueous suspensions
      using microwave (MW) powered electrodeless discharge lamps (EDLs) was studied. MB
      of initial concentration 100 mg/l was mainly decomposed in the process of
      photocatalytic degradation using EDLs (PCD/EDLs) after 15 min of irradiation. The
      corresponding mineralization efficiency was 45%. The influence of factors as
      EDLs, solution volume and TiO(2) catalyst dosage on the decomposition of MB in
      the PCD/EDLs process was also investigated. The optimal decomposition efficiency
      was observed when EDLs-4 (four 10 mm x 50 mm EDLs), solution volume of 50 ml and
      TiO(2) catalyst dosage of 1-4 g/l were used in the study. The PCD/EDLs process
      was promising in treating MB polluted water.

PMID- 16297537
TI  - Toxicity assessment of pesticides to Pseudokirchneriella subcapitata under air
      tight test environment.
AB  - This paper presents the toxicity data of seven pesticides including atrazine,
      parathion, dichlorvos, malathion, fenthion, 2-methyl-4-chlorophenoxyacetic acid,
      and pentachlorophenol on Pseudokirchneriella subcapitata based on a new algal
      toxicity testing technique conducted under air-tight environment. The dissolved
      oxygen production and the cell density were adopted as the response endpoints.
      Median effective concentrations (EC50) range from 0.0035 to 3.40 mg/L (DO
      production) and from 0.0067 to 3.12 mg/L (cell density). No-observed-effect
      concentration (NOEC) was determined using the Dunnett's test. NOEC values are
      with in the range of 0.001-1.20 mg/L. In general, the two test endpoints revealed
      similar sensitivities. From comparisons of literature data also based on
      Pseudokirchneriella subcapitata, it is clear that conventional batch tests tend
      to underestimate the toxicity of pesticides due to their open test environment.
      Closed-system tests, i.e., microplate test, respirometer test, and our BOD-bottle
      test, generally provide better assessment to the effects of pesticides. Data
      based on our test method reveals much higher toxicity (3-100 times) than that
      from the conventional batch tests. Furthermore, for organophosphorus
      insecticides, results from the present study show that Pseudokirchneriella
      subcapitata is less sensitive than Daphnia magna and rainbow trout, but is more
      susceptible than fathead minnow. The closed-system test applied in this study
      provides more adequate assessment for the toxicity of pesticides than the
      conventional batch tests.

PMID- 16297538
TI  - Distribution of polychlorinated dibenzo-p-dioxins and dibenzofurans in the
      landfill site for solidified monoliths of fly ash.
AB  - One landfill site, which co-treated solidified monoliths of fly ash and bottom
      ash, was investigated comprehensively to characterize its PCDD/F distribution.
      The solidified monoliths, soil, banyan leaves, groundwater in the monitoring
      wells and the treated landfill leachates in this landfill site for solidified
      monoliths of fly ash were all sampled to clarify their PCDD/F characteristics.
      Although the PCDD/F leaching concentrations were extremely lower than the Taiwan
      PCDD/F TCLP regulation of solidified monoliths, the PCDD/F contents in the
      surface soils of the landfill site are 460 times higher than that of urban soils
      and the highest value is 2.8 times higher than the Taiwan soil regulation (1000
      ngI-TEQkg(-1)). The elevated PCDD/F contents in the soil reveal their potential
      for causing adverse health risk for humans, including the pathway of resuspension
      of soil particles and volatilization of PCDD/Fs from soil. The PCDD/F
      concentrations in the groundwater and the treated landfill leachates of the
      landfill site for solidified monoliths were both higher than that in the control
      samples, suggesting its potential to be a PCDD/F source of nearby water
      environment. Without proper control and management, landfill sites for solidified
      monoliths of fly ash can seriously hazard the surrounding environment, therefore,
      are important to consider.

PMID- 16297539
TI  - Galvanic sludge metals recovery by pyrometallurgical and hydrometallurgical
      treatment.
AB  - This paper reports a study, on laboratory scale, of sulphating roasting to
      perform a treatment for a selective recovery of valuable metals from galvanic
      sludge. The target metals were copper, zinc and nickel and the sulphating agent
      used was pyrite, from coal wastes. The particularity of this treatment is the use
      of two hazardous wastes as raw material. They are generated in large quantities
      at coal extraction sites (coal wastes) and at plating shops (galvanic sludge).
      The wastes were characterized by X-ray fluorescence (XRF), particle size
      distribution and water contents. The chemical characterization showed sludges
      with high copper concentration, with more than 14% (dry base). In the roasting
      step, the galvanic sludge was mixed with pyritic waste and the parameters
      evaluated were galvanic sludge/pyrite ratio, roasting temperature and roasting
      time. After roasting, the product of reaction was leached with water in room
      temperature for 15 min. Considering that other studies have already demonstrated
      that the pyrometallurgical step determines the process efficiency, this paper
      only reports the influence of pyrometallurgical parameters. Hydrometallurgical
      processes will be better evaluated in further studies. The conditions that best
      reflect a compromise between the valuable metal recover and the economical
      viability of the process were achieved for 1:0.4 galvanic sludge/pyrite ratio, 90
      min of roasting time and 550 degrees C of roasting temperature. These conditions
      lead to a recovery of 60% zinc, 43% nickel and 50% copper.

PMID- 16297540
TI  - Biosorption of nickel(II) ions onto Sargassum wightii: application of two
      parameter and three-parameter isotherm models.
AB  - Biosorption of nickel(II) ions from aqueous solution onto Sargassum wightii has
      been studied and the equilibrium isotherms were determined. The experimental data
      obtained at different pH conditions (pH 3.0-4.5) have been analyzed using five
      two-parameter models (Langmuir, Freundlich, Temkin, Dubinin-Radushkevich and
      Flory-Huggins) and five three-parameter models (Redlich-Peterson, Sips, Khan,
      Radke-Prausnitz and Toth). In order to determine the best fit isotherm, three
      error analysis methods were used to evaluate the data: correlation coefficient,
      residual root mean square error and chi-square test. The error analysis
      demonstrated that the three-parameter models better described the nickel
      biosorption data compared to two-parameter models. In particular, Toth equation
      provided the best model for nickel biosorption data at all pH conditions
      examined.

PMID- 16297541
TI  - In-situ degradation of sulphur mustard and its simulants on the surface of
      impregnated carbon systems.
AB  - Bis-2-chloroethyl sulphide (sulphur mustard or HD) is an extremely toxic and
      persistent chemical warfare agent. For in situ degradation of HD and its
      analogues (simulants), i.e., dibutyl sulphide (DBS) and ethyl 2-hydroxyethyl
      sulphide (HEES), different carbon systems such as 11-molybdo-1-vanadophosphoric
      acid impregnated carbon (V(1)/C), ruthenium chloride impregnated carbon (Ru/C)
      and combination of these two (V(1)/Ru/C) were prepared. These carbons were
      characterized for cumulative micropore volume and surface area by N(2) BET. The
      kinetics of the in situ degradation of HD and its simulants were studied and
      found to be following the first order kinetics. Kinetic rate constants and t(1/2)
      values were determined. Products were characterized using NMR, IR and GC-MS.
      Reaction products were found to be sulphoxide and sulphone. The combined system,
      i.e., 11-molybdo-1-vanadophosphoric acid plus ruthenium chloride (V(1)/Ru/C) was
      found to be best for in-situ degradation of HD and its simulants. In-situ
      degradation by polyoxometalate based system was found to be stoichiometry based
      while Ru/C oxidized HD in presence of chemisorbed oxygen. In combined system of
      V(1)/Ru/C ruthenium worked as a catalyst and polyoxometalate acted as a source of
      oxygen. Effect of moisture was also studied in combined system. Rate of
      degradation of HD was found to be increasing with increased percentage of
      moisture content.

PMID- 16297542
TI  - Treatment of levafix orange textile dye solution by electrocoagulation.
AB  - The decolorization of the levafix orange textile dye in aqueous solution by
      electrocoagulation using aluminum sacrificial anode has been investigated. The
      process performance is analyzed in terms of decolorization efficiency and the
      important cost-related parameters such as electrode and energy consumptions, as a
      function of initial pH, conductivity, current density, initial dye concentration
      and electrolysis time. The present study proves the effectiveness of
      electrochemical treatment for the textile dye solution. 95% decolorization
      efficiency may be obtained at suitable operating conditions such as; current
      density 100 A/m(2), operating time 12 min and initial pH 6.4. The corresponding
      electrode and energy consumptions during the electrolysis were found to be 1.8 kg
      Al/kg dye and 35 k Wh/kg dye.

PMID- 16297544
TI  - Real time monitoring of hazardous airborne chemicals: a styrene investigation.
AB  - The low level detection of air pollutants requires reliable sampling and
      calibration techniques, as well as using sophisticated analytical
      instrumentation. Incorporating these requirements into a mobile platform allows
      for accurate, curb side measurement of airborne ambient chemicals in real time.
      In this case study, air emissions from two manufacturing facilities in close
      proximity to each other were monitored with a mobile unit to chemically
      characterize and differentiate the emissions from each facility. Based upon the
      downwind fingerprinting and concentration levels, the mobile unit was able to
      isolate the source of the emissions to the responsible facility. A few chemicals
      which were detected by the TAGA had never been reported by the companies. Real
      time proximity monitoring was accomplished by using a triple quadrupole mass
      spectrometer (TAGA IIe). The TAGA IIe interfaces with a low pressure chemical
      ionization source that operates at 3 Torr and 100 microA. By monitoring the
      response of specific parent/daughter ion pairs, the TAGA IIe unit was able to
      determine the point-of-impingement concentrations of styrene and other ambient
      airborne chemicals. Positive identification and quantitation of styrene was
      accomplished by multiple measurements of the following ion pairs: 104/78, 104/77,
      104/65 and 104/52. By optimizing various parameters of the TAGA IIe a method
      detection limit of 1.1 microg/m(3) was achieved for styrene. A daily multi-point
      calibration was performed using a liquid standard. The maximum half-hour average
      concentration of styrene measured downwind of the two facilities was 2300
      microg/m(3) and the maximum instantaneous level was measured at 15,000
      microg/m(3). The mobile capability of the unit was also utilized in determining
      the ambient airborne concentration of styrene at various distances from the
      companies with the maximum levels measured at close proximity to the emission
      sources.

PMID- 16297543
TI  - Statistical design of experiments as a tool for optimizing the batch conditions
      to Cr(VI) biosorption on Araucaria angustifolia wastes.
AB  - In order to reduce the total number of experiments for achieving the best
      conditions for Cr(VI) uptake using Araucaria angustifolia (named pinhao) wastes
      as a biosorbent, three statistical design of experiments were carried out. A full
      2(4) factorial design with two blocks and two central points (20 experiments) was
      experimented (pH, initial metallic ion concentration-C(o), biosorbent
      concentration-X and time of contact-t), showing that all the factors were
      significant; besides, several interactions among the factors were also
      significant. These results led to the performance of a Box-Behnken surface
      analysis design with three factors (X, C(o) and t) and three central points and
      just one block (15 experiments). The performance of these two statistical designs
      of experiments led to the best conditions for Cr(VI) biosorption on the pinhao
      wastes using a batch system, where: pH 2.0; C(o) = 1200 mg l(-1) Cr(VI); X = 1.5
      g l(-1) of biosorbent; t = 8 h. The maximum Cr(VI) uptake in these conditions was
      125 mg g(-1). After evaluating the best Cr(VI) biosorption conditions on pinhao
      wastes, a new Box-Behnken surface analysis design was employed in order to verify
      the effects of three concomitant ions (Cl(-), NO(3)(-) and PO(4)(3-)) on the
      biosorption of Cr(VI) as a dichromate on the biosorbent (15 experiments). These
      results showed that the tested anions did not show any significant effect on the
      Cr(VI) uptake by pinhao wastes. In order to evaluate the pinhao wastes as a
      biosorbent in dynamic system, a glass column was fulfilled with pinhao wastes
      (4.00 g) as biosorbent, and it was fed with 25.0 mg l(-1) Cr(VI) at pH 2.0 and
      2.5 ml min(-1). The breakpoint was attained when concentrations of effluent of
      the column attained the value of 0.05 mg l(-1) Cr(VI) using 5550 ml of the
      metallic ion solution. In these conditions, the biosorbent was able to remove
      completely Cr(VI) from aqueous solution with a ratio of Cr(VI) effluent
      volume/biosorbent volume of 252.3.

PMID- 16297545
TI  - Overall characterization of cork dust explosion.
AB  - Explosibility and ignitability studies of air/cork dust mixtures were conducted
      in a near-spherical 22.7 L explosibility test chamber using pyrotechnic ignitors
      and in a furnace of 1.23 L. The suspension dust burned as air-dispersed dust
      clouds and the uniformity of the dispersion inside the chamber was evaluated
      through optical dust probes. The range of tested particle sizes went from a mass
      median diameter of 47.4 to 438.3 microm and the covered dust cloud concentration
      was up to 700-800 g/m(3). Measured explosion parameters included minimum
      explosible concentration, maximum explosion pressure, maximum rate of pressure
      rise and minimum autoignition temperature. The effect of dust particle size on
      flammability was evaluated and it was found that the minimum explosible
      concentration is around 40 g/m(3) and it is relatively independent of particle
      size below 180 microm. Maximum explosion pressure of 7.2 bar and maximum rate of
      pressure rise of 179 bar/s were detected for the smallest tested sizes. The
      limitations on the rates of devolatilization of the solid particles became rate
      controlling at high burning velocities, at high dust loadings and for large
      particle sizes. The effect of initial pressure on the characteristic parameters
      of the explosion was studied by varying the initial absolute pressure from 0.9
      bar to 2.2 bar, and it was found that as initial pressure increases, there is a
      proportional increase of minimum explosion limit, maximum explosion pressure, and
      maximum rate of pressure rise. The influence of the intensity of the ignition
      energy on the development of the explosion was evaluated using ignition energies
      of 1000 J, 2500 J and 5000 J, and the experimental data showed that the value of
      2500 J is the most convenient to use in the determination of minimum explosion
      concentration. The behavior of the cork dust explosion in hybrid methane air
      mixtures was studied for atmospheres with 2% and 3.5% (v/v) of methane. The
      effect of methane content on the characteristic parameters of the explosions was
      evaluated. The conclusion is that, the hazard and explosion danger rise with the
      increase of methane concentration, characterized by the reduction of the minimum
      dust explosion concentration. The minimum autoignition temperature obtained with
      the thermal ignition tests was 540 degrees C and the results have shown that this
      value is independent of particle size, for particles with mass median diameters
      below 80 microm.

PMID- 16297546
TI  - Extent of oxidation of Cr(III) to Cr(VI) under various conditions pertaining to
      natural environment.
AB  - Calculations show that oxidation of chromium oxide (Cr2O3) by oxygen and
      oxidation of chromium hydroxide (Cr(OH)3) by manganese dioxide (MnO2) are
      thermodynamically feasible in both aerobic and mildly anoxic environments.
      Experiments were carried out to determine the rate and extent of chromium
      oxidation under various conditions, i.e., when Cr2O3 was heated in the presence
      of oxygen, when Cr(OH)3 and MnO2 mixtures were suspended in aerobic or anoxic
      aqueous media at various pH values, when Cr(OH)3 and MnO2 mixtures interacted in
      moist aerobic conditions and when chromium assumed to be Cr(OH)3 and manganese
      assumed to be MnO2 interacted in the presence of competing electron
      donors/acceptors, as is the case in chromium-contaminated sludge. Results
      indicate that trivalent chromium in Cr2O3 could be readily converted to
      hexavalent chromium at a temperature range of 200-300 degrees C, with conversion
      rates of up to 50% in 12 h. In aqueous media, Cr(OH)3 was slowly converted to
      dissolved Cr(VI) in the presence of MnO2, both in aerobic and anoxic conditions,
      with conversion rates of up to 1% in 60 days. In moist aerobic conditions and in
      the presence of MnO2, Cr(OH)(3) slowly converted to hexavalent chromium, with up
      to 0.05% conversion observed in 90 days. Chromium oxidation also occurred in
      sludge samples, especially under aerobic conditions. However, such transformation
      was found to be transitory, with the Cr(VI) formed being ultimately reduced back
      to Cr(III) due to the presence of various reducing agents in the sludge.
      Nevertheless since up to 17% conversion of Cr(III) to Cr(VI) occurred in sludge
      under aerobic conditions by 30 days, there is real danger under field conditions
      of spreading Cr(VI) pollution due to possible intervening rainfall, runoff and
      percolation.

PMID- 16297547
TI  - Lead recovery from PbZrO3 using wet ball-mill technique and hydrothermal
      synthesis of alpha-zirconium phosphate from wastewater for resource recovery.
AB  - Lead recovery from lead zirconate (PbZrO(3)) ceramics was investigated using a
      wet ball-mill treatment in H(2)SO(4) aqueous solution. Subsequently crystalline
      alpha-zirconium phosphate (alpha-Zr(HPO(4))(2).H(2)O) was synthesized using a
      hydrothermal technique in order for the resource recovery of zirconium in the
      wastewater after the wet ball-mill treatment. A wet ball-mill treatment in 4.5M
      H(2)SO(4) aqueous solution for 24h was capable of converting more than 99.9% of
      the Pb initially included in the PbZrO(3) to solid state PbSO(4) with a purity of
      98%. On the other hand, the Zr in the PbZrO(3) was dissolved into the acidic
      solution during the treatment. The Pb and Zr metal elements coexisting in
      PbZrO(3) were successfully separated by the wet ball-mill technique. Then,
      resource recovery of zirconium in the wastewater was examined. Crystalline alpha
      Zr(HPO(4))(2).H(2)O was synthesized by hydrothermal treatments in 3.1-12.5M
      H(3)PO(4) aqueous solutions at temperatures of 120-240 degrees C for a duration
      of 70h. The hydrothermally prepared powders were characterized by X-ray
      diffraction (XRD) and scanning electron microscopy (SEM), and then they were also
      evaluated in terms of cation exchange capacity (CEC) measurement and
      thermogravimetric (TG) analysis.

PMID- 16297548
TI  - Anaerobic stabilisation of sludge produced during municipal wastewater treatment
      by electrocoagulation.
AB  - Anaerobic digestion of sludge from small electrocoagulation wastewater treatment
      plant (SEWWTP) is described. The sludge for digestion (SEWWTP sludge) was taken
      from pilot-scale SEWWTP with the capacity of about 200-population equivalent (25
      m3 of municipal wastewater per day). Due to the technology of wastewater
      treatment, the characteristics of SEWWTP sludge was different from sludge
      produced in conventional mechanical-biological wastewater treatment plant.
      Therefore, experiments were focused on possibilities of anaerobic sludge
      digestion and determination of conditions and parameters (amount and quality of
      the sludge, biogas production, etc.). Average COD removal efficiency in the pilot
      scale SEWWTP exceeded 80%. Organic content of excess sludge (volatile suspended
      solids (VSS)) was in the range of 52.1-59.2% (these values are much lower
      compared to VSS content in raw sludge from conventional municipal wastewater
      treatment plant, where VSS is about 75%). Biogas production from anaerobic
      digestion of SEWWTP sludge was approximately three times lower compared to
      standard production in conventional municipal wastewater treatment plant. Low pH
      (6.5-6.7), high concentration of iron (up to 1400 mg/L) and aluminium (up to 1300
      mg/L) and very low (almost zero) concentration of dissolved phosphorus in sludge
      water were the main factors limiting the rate of anaerobic processes. Based on
      these results, anaerobic digestion of SEWWTP sludge was not recommended as an
      appropriate stabilisation method.

PMID- 16297549
TI  - Melatonin enhances NADPH-diaphorase activities in the hypothalamus of maternally
      separated rats.
AB  - Maternal separation or social isolation is a risk factor in the development of
      mammalian species affecting both physical and mental growth, and food intake
      regulation. Melatonin has been known to regulate body weight on various species
      including rodents. We investigated the effect of melatonin treatment on the
      expression of nitric oxide synthase, which may involved in food intake
      regulation, in the brain of maternally separated-rats using nicotinamide adenine
      dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Melatonin (10 mg/kg
      i.p.) was injected to 14-day-old maternally-separated rats for 7 days. Maternally
      separated rats with melatonin administration showed significantly higher staining
      intensities of NADPH-d-positive neurons in the paraventricular nucleus (PVN) and
      in lateral hypothalamic area (LHA) than maternally-separated without melatonin
      administration (P < 0.05). Body weight of melatonin treated rats significantly
      increased at the 6th and 7th day compared to that of rats without melatonin
      treatment (P < 0.05). These results indicate that melatonin may be associated
      with increase body weight via NOS in the hypothalamic areas in maternally
      separated or socially isolated rats.

PMID- 16297550
TI  - Autophagy of amyloid beta-protein in differentiated neuroblastoma cells exposed
      to oxidative stress.
AB  - Oxidative stress is considered important for the pathogenesis of Alzheimer
      disease (AD), which is characterized by the formation of senile plaques rich in
      amyloid beta-protein (Abeta). Abeta cytotoxicity has been found dependent on
      lysosomes, which are abundant in AD neurons and are shown to partially co
      localize with Abeta. To determine whether oxidative stress has any influence on
      the relationship between lysosomes and Abeta1-42 (the most toxic form of Abeta),
      we studied the effect of hyperoxia (40% versus 8% ambient oxygen) on the
      intracellular localization of Abeta1-42 (assessed by immunocytochemistry) in
      retinoic acid differentiated SH-SY5Y neuroblastoma cells maintained in serum-free
      OptiMEM medium. In control cells, Abeta1-42 was mainly localized to small non
      lysosomal cytoplasmic granules. Only occasionally Abeta1-42 was found in large
      (over 1 microm) lysosomal-associated membrane protein 2 positive vacuoles, devoid
      of the early endosomal marker rab5. These large Abeta1-42 -containing lysosomes
      were not detectable in the presence of serum (known to suppress autophagy), while
      their number increased dramatically (up to 24-fold) after exposure of cells to
      hyperoxia during 5 days. Activation of autophagy by hyperoxia was confirmed by
      transmission electron microscopy. Furthermore, an inhibitor of autophagic
      sequestration 3-methyladenine prevented the accumulation of Abeta1-42 -positive
      lysosomes due to hyperoxia. In parallel experiments, intralysosomal accumulation
      of Abeta1-40 following oxidative stress has been found as well. The results
      suggest that Abeta can be autophagocytosed and its accumulation within neuronal
      lysosomes is enhanced by oxidative stress.

PMID- 16297551
TI  - Neonatal immune challenge alters nociception in the adult rat.
AB  - Intense pain or intense peripheral inflammation experienced during development
      can have pronounced effects upon adult pain sensation. However, little is known
      about the more commonly encountered mild systemic inflammation, such as that
      experienced with mild illness. Neonatal exposure to lipopolysaccharide (LPS), an
      established model of immune system activation, has been shown to affect febrile
      and cyclooxygenase-2 (COX-2) responses to a similar exposure in adulthood. Adult
      LPS also elicits a range of sickness behaviours, including enhanced responses to
      painful stimuli. We, therefore, hypothesized that adult sensation and pain
      responses could be affected by a neonatal LPS challenge. Male and female Sprague
      Dawley rats were administered LPS at postnatal day 14 and were tested in
      adulthood for nociceptive responses to thermal and mechanical stimuli using,
      respectively, a plantar test apparatus and von Frey filaments, before and after
      adult LPS. Expression of dorsal root ganglion and lumbar spinal cord COX-2 was
      also examined. Animals treated as neonates with saline showed the expected
      hypersensitivity to painful stimuli after adult LPS as well as enhanced spinal
      cord COX-2. Neonatally LPS-treated rats, however, showed a significantly
      different profile. They displayed enhanced baseline nociception and elevated
      basal spinal cord COX-2 compared with neonatally saline-treated rats. Also,
      rather than the expected hyperalgesia after adult LPS, no changes in nociceptive
      responses and a reduction in spinal cord COX-2 expression were observed. These
      findings have important implications for the understanding of pain and its
      management and highlight the importance of the neonatal period in the development
      of pain pathways.

PMID- 16297552
TI  - The economic impact of chronic pain in adolescence: methodological considerations
      and a preliminary costs-of-illness study.
AB  - Chronic pain in adulthood is one of the most costly conditions in modern western
      society. However, very little is known about the costs of chronic pain in
      adolescence. This preliminary study explored methods for collecting economic
      related data for this population and estimated the cost-of-illness of adolescent
      chronic pain in the United Kingdom. The client service receipt inventory was
      specifically adapted for use with parents of adolescent chronic pain patients to
      collect economic-related data (CSRI-Pain). This method was compared and discussed
      in relation to other widely used methods. The CSRI-Pain was sent to 52 families
      of adolescents with chronic pain to complete as a self-report retrospective
      questionnaire. These data were linked with unit costs to estimate the total care
      cost package for each family. The economic impact of adolescent chronic pain was
      found to be high. The mean cost per adolescent experiencing chronic pain was
      approximately 8,000 pounds per year, including direct and indirect costs. The
      adolescents attending a specialised pain management unit, who had predominantly
      non-inflammatory pain, accrued significantly higher costs, than those attending
      rheumatology outpatient clinics, who had mostly inflammatory diagnoses.
      Extrapolating the mean total cost to estimated UK prevalence data of adolescent
      chronic pain demonstrates a cost-of-illness to UK society of approximately 3,840
      million pounds in one year. The implications of the study are discussed.

PMID- 16297553
TI  - Increased levels of interstitial potassium but normal levels of muscle IL-6 and
      LDH in patients with trapezius myalgia.
AB  - The mechanisms behind the development of work-related trapezius pain are
      suggested to involve both peripheral and central components, but the specific
      contribution of alterations in muscle nociceptive and other substances is not
      clear. Female patients with chronic trapezius myalgia (N=19; TM) and female
      controls (N=20; CON) were studied at rest, during 20 min repetitive low-force
      exercise and recovery, and had their interstitial concentrations of potassium
      (K(+)), lactate dehydrogenase (LDH), interleukin-6 (IL-6) and collagen turnover
      determined in the trapezius muscle by the microdialysis technique. K(+) levels
      were at all time points higher in TM than in CON (P<0.0001). Baseline levels of
      LDH and IL-6 were similar in both groups. In response to exercise pain intensity,
      rated perceived exertion, and the concentrations of K(+), LDH and IL-6 increased
      significantly in both groups. [K(+)] immediately decreased to baseline levels in
      CON but remained elevated during the first 20 min of recovery in TM (P<0.01)
      whereafter it returned to baseline level. In all subjects taken together mean
      [K(+)] correlated negatively with pressure pain threshold of trapezius (P<0.001),
      positively with mean pain intensity VAS (P<0.001) and mean perceived exertion
      (P<0.001). Rises in muscle LDH and IL-6 as well as the anabolic ratio for
      collagen type I was not significantly different between groups. In conclusion,
      patients with chronic pain in the trapezius muscle had increased levels of
      interstitial potassium. This finding could be causally related to myalgia or
      secondary to pain due to deconditioned muscle or altered muscle activity pattern.

PMID- 16297554
TI  - Sustained sleep restriction reduces emotional and physical well-being.
AB  - BACKGROUND: Chronic insufficient sleep is a common finding in many pain-related
      and other medical diseases and is frequently experienced in the general
      population. Prolonged curtailment of nocturnal sleep has been studied for its
      adverse effect on cognitive functioning and subjective tiredness, but relatively
      little is known about its effect on mood and physical symptoms. OBJECTIVE: In
      order to test whether sleep restriction to 50% of the habitual time over 12 days
      affects diurnal and day-to-day variation of subjective ratings of mood and
      physical symptoms, 108 adjectives and statements were self-rated using visual
      analog scales every 2h during the waking period. DESIGN: Randomized, 16-day
      controlled in-laboratory study. SETTING: General Clinical Research Center (GCRC).
      PARTICIPANTS: Forty healthy subjects aged 21-40 years (14 females, 26 males).
      INTERVENTION: Subjects were randomized to either 4h of sleep per night (11 pm-3
      am, N=22) or 8h of sleep per night (11 pm-7 am, N=18) for 12 consecutive days.
      MAIN OUTCOME MEASURE: Changes in the factor-derived variables optimism
      sociability, tiredness-fatigue, anger-aggression, bodily discomfort, and items
      constituting bodily discomfort were compared between groups. RESULTS: Optimism
      sociability progressively declined over consecutive days of sleep restriction by
      15%. Bodily discomfort showed a slight, but significant interindividual increase
      of 3% across days of sleep restriction due to significant increases of
      generalized body pain, back pain, and stomach pain. Optimism-sociability and
      tiredness-fatigue showed diurnal variations with a quadratic function period
      within each day in both conditions. CONCLUSION: The data suggest that chronic
      insufficient sleep may contribute to the onset and amplification of pain and
      affect health by compromising optimistic outlook and psychosocial functioning.

PMID- 16297555
TI  - An experimental study of viscero-visceral hyperalgesia using an ultrasound-based
      multimodal sensory testing approach.
AB  - Widespread visceral hypersensitivity and the overlap of symptom complexes
      observed in functional gastrointestinal disorders may be related to central
      sensitization and neuroplastic changes. A multimodal and multi-segmental model
      was developed to evaluate viscero-visceral hyperalgesia induced by experimental
      esophageal sensitization in healthy volunteers. Twelve healthy subjects were
      studied using a double-blinded, placebo-controlled design. The sensitivity to
      mechanical and heat stimulations was assessed in the proximal esophagus, duodenum
      and rectum before and after perfusion of the distal esophagus with acid or
      saline. A special-designed probe was used allowing cross-sectional ultrasound
      imaging during mechanical and heat stimulation of the esophagus and duodenum.
      Another probe was used for mechanical stimulation of the rectum. The referred
      somatic pain areas to gut pain stimulations were also assessed. Following acid
      perfusion 11 of 12 volunteers showed increased sensitivity to one or more
      stimulation modalities. An overall increased sensitivity to mechanical stretch in
      the three gut segments was seen (P=0.0001). Posthoc analysis showed that this was
      mainly due to increased sensitivity in the rectum (P<0.001). No changes were seen
      to thermal stimulations (all P-values>0.4). The somatic referred pain area to
      duodenal stimulations increased (P=0.04), while it was unaffected to esophageal
      and rectal stimulations (P>0.3). The present method demonstrated a new approach
      to assess multimodal sensitivity to experimental sensitization of the esophagus
      and related viscero-visceral hyperalgesia. Central mechanisms can explain the
      remote hyperalgesia to mechanical visceral stimulation and the increase in
      referred pain areas. The present method may be used to explore pathophysiology
      and pharmacological interventions in patients with visceral hypersensitivity.

PMID- 16297556
TI  - Excitatory amino acid concentrations increase in the spinal cord dorsal horn
      after repeated intramuscular injection of acidic saline.
AB  - Chronic muscle pain is common and often difficult to treat. In this study, we
      further characterize a model of chronic muscle pain induced by repeated
      intramuscular injection of acidic saline. Two injections of acid into muscle
      separated by 5 days result in secondary mechanical hyperalgesia that lasts for up
      to 4 weeks. Blockade of spinal NMDA receptors prior to the second injection
      intramuscular acid injection delays the onset of hyperalgesia, where as the
      maintenance phase of hyperalgesia, evaluated 1 week after the second
      intramuscular injection, is dependent on activation of spinal AMPA/kainate and
      NMDA receptors. In order to determine if behavioral hyperalgesia and glutamate
      receptor involvement are associated with increased concentrations of excitatory
      amino acids (EAA), we utilized microdialysis to evaluate extracellular glutamate
      and aspartate concentrations in the spinal dorsal horn during the first and
      second intramuscular acid injections, and 1 week after the development of
      mechanical hyperalgesia. The second intramuscular injection evoked a calcium
      dependent increase in both spinal glutamate and aspartate concentrations.
      Glutamate concentrations within the dorsal horn were also increased 1 week after
      the second acid injection. Our data suggest increased release of spinal EAAs in
      the dorsal horn contributes to the development and maintenance of hyperalgesia.

PMID- 16297558
TI  - Behavioral changes and trigeminal ganglion sodium channel regulation in an
      orofacial neuropathic pain model.
AB  - We used a photochemical method to generate a partial ischemic injury to the
      infraorbital branch of the trigeminal nerve in rats. Following injury, rats
      developed a bilateral persistent hypersensitivity to mechanical stimulation in
      the territory innervated by the infraorbital nerve. In addition, spread of
      mechanical hypersensitivity beyond the facial region was noted. Heat
      hypersensitivity was also present, although to a lesser extent and of a shorter
      duration. In some rats, excessive facial grooming/scratching were observed.
      Morphological examination revealed a graded damage to the irradiated portion of
      the infraorbital nerve that was related to the duration of laser irradiation.
      Investigations of gene expression changes in injured trigeminal ganglion neurons
      of animals with behavioral signs of neuropathic pain demonstrated that the sodium
      channel alpha-subunit Na(v)1.3-absent in sham-operated animals-was expressed to a
      limited extent. mRNAs for Na(v)1.8 and Na(v)1.9 were reduced both with respect to
      proportions of expressing neurons and to intensities, whereas the beta 3 subunit
      was markedly upregulated. mRNA levels of p11, a regulatory factor that
      facilitates the surface expression of Na(v)1.8, were unchanged. Previous findings
      have shown that injury to the trigeminal nerve branches may elicit responses that
      differ from those of segmental spinal nerves. Despite this we conclude that the
      key sodium channel regulations that are reported as consequences of nerve damage
      in the dorsal root ganglia seem to appear also in the trigeminal ganglion. Thus,
      novel analgesic drugs designed to target the sodium channel subtypes involved
      could be of use for the treatment of orofacial pain.

PMID- 16297557
TI  - Development and validation of a dental pain-screening questionnaire.
AB  - Dental pain, estimated to affect 12-40% of community-dwelling adults, is a
      symptom of a wide range of clinical conditions. A population screening instrument
      is needed to study their prevalence. This project aimed to develop a
      questionnaire for classifying a sample of dental pain patients into three groups
      of common dental pain conditions, i.e. Group 1 (Acute periapical periodontitis
      and Irreversible pulpitis), Group 2 (Reversible pulpitis and Dentine
      hypersensitivity) and Group 3 (Pericoronitis). Initial items were generated
      through a literature review, individual unstructured patient interviews and
      consultation with experts. Items generated were administered to a sample of
      dental pain patients for self-completion. Responses were subjected to a series of
      factor and discriminant analyses to identify questions capable of differentiating
      the sample into three groups, originally categorized by clinical diagnosis, with
      high classification rates. The selected items were administered to a further
      sample of dental pain patients to test for its sensitivity and specificity in
      classifying the sample into three groups against the gold standard of clinical
      diagnosis. The final 16-item Dental Pain Questionnaire (DePaQ) was capable of
      correctly classifying 89.7% of dental pain cases initially categorized by
      clinical diagnoses. The sensitivity of the questionnaire was 0.80-Group z1, 0.85
      Group 2 and 0.59-Group 3. Specificity was 0.83-Group A1, 0.89-Group A2 and 0.90
      Group 3. The DePaQ, which can easily be administered by non-clinical personnel,
      may be used to collect epidemiological data on common dental pain conditions,
      assess dental needs for a specified population, and triage of patients seeking
      treatment for dental pain.

PMID- 16297559
TI  - Effects of pre-treatment with amantadine on morphine induced antinociception
      during second phase formalin responses in rats.
AB  - The clinically available NMDA-receptor antagonist drug, amantadine, has been
      shown to result in morphine sparing effects in humans after surgery. However, no
      data are available to describe the exact form of interaction. The present study
      aims to profile the possible effects of amantadine (0, 12.5, 25 or 50 mgkg(-1)
      i.p.) pre-treatment on morphine (0, 0.63, 1.25, 2.5 or 5 mgkg(-1) s.c.) induced
      antinociception in rats. The (automated) formalin test (5% formalin, 50 microl)
      was used to assess if amantadine enhances the antinociceptive activity of
      morphine. Possible motor impairment was assessed with a rotarod test. Morphine
      was measured in serum of amantadine or vehicle treated rats to search for
      possible pharmacokinetic interactions between amantadine and morphine.
      Isobolographic analysis provided evidence for a synergistic interaction between
      amantadine and morphine in the second phase of the formalin test. No evidence was
      found to indicate that amantadine induced motor impairment at the doses
      potentiating morphine during the second phase of the formalin test. There was no
      evidence for a pharmacokinetic interaction between amantadine and morphine.
      Since, the second phase of the formalin test is dependent on activation of the
      NMDA receptor system it is concluded that an antagonistic activity of amantadine
      at the NMDA receptor most likely contributes to the synergistic interaction
      observed between amantadine and morphine in rats.

PMID- 16297560
TI  - Effect of genetic knockout or pharmacologic inhibition of neuronal nitric oxide
      synthase on complete Freund's adjuvant-induced persistent pain.
AB  - Nitric oxide (NO) acts as a neurotransmitter or neuromodulator involving in the
      modulation of thermal and/or inflammatory hyperalgesia. The neuronal nitric oxide
      synthase (nNOS) is a key enzyme for NO production in normal neuronal tissues, but
      its functional role in chronic pain remains unclear. The present study combined a
      genetic strategy with a pharmacologic approach to address the role of nNOS in the
      central mechanism of complete Freund's adjuvant (CFA)-induced chronic
      inflammatory pain. Targeted disruption of the nNOS gene significantly reduced CFA
      induced mechanical pain hypersensitivity during the maintenance (but not the
      development) of inflammatory pain, while it failed to attenuate either
      development or maintenance of CFA-induced thermal pain hypersensitivity.
      Intraperitoneal administration of L-N(G)-nitro-arginine methyl ester (L-NAME), a
      non-specific NOS inhibitor, blocked CFA-evoked thermal and mechanical pain
      hypersensitivity at both development (2h) and maintenance (24h) phase in wild
      type mice, but had no effect in the knockout mice. Furthermore, intrathecal
      injection of either L-NAME or 7-nitroindazole, a selective nNOS inhibitor,
      markedly attenuated mechanical pain hypersensitivity at both 2 and 24h after CFA
      injection. Finally, spinal cord nNOS (but not endothelial NOS or inducible NOS)
      expression was up-regulated at 24h after CFA injection, occurring mainly in the
      ipsilateral superficial dorsal horn. Together, these data indicate that spinal
      cord nNOS may be essential for the maintenance of mechanical pain
      hypersensitivity and that it may also be sufficient for the development of
      mechanical pain hypersensitivity and for the development and maintenance of
      thermal pain hypersensitivity after chronic inflammation. Our findings suggest
      that spinal cord nNOS might play a critical role in central mechanisms of the
      development and/or maintenance of chronic inflammatory pain.

PMID- 16297561
TI  - Comment on Hendriks et al.: prognostic factors for poor recovery in acute
      whiplash patients. Pain 2005;114:408-416.

PMID- 16297562
TI  - Illness burden mediates the relationship between pain and illicit drug use in
      persons living with HIV.
AB  - We investigated predictive and concurrent relationships among reported pain,
      HIV/AIDS illness burden, and substance use history in 2,267 participants in the
      longitudinal HIV Cost and Services Utilization Study (HCSUS). Substance use
      history was classified as screening positive for current illicit drug use
      (N=253), past drug use (N=617), and non-user (N=1,397) at baseline. To control
      for demographic correlates, age, sex and socioeconomic status (SES) were included
      as predictors. Covariance structure models indicated greater pain at baseline
      among participants acknowledging current substance use. Pain at baseline was also
      directly predicted by greater HIV/AIDS illness burden, lower SES, and older age.
      At 6 months, pain was directly predicted by prior pain, worse concurrent HIV/AIDS
      illness burden and female sex. At 12 months, pain was predicted by older age,
      prior pain, and concurrent HIV/AIDS illness. It was also modestly but
      significantly predicted by current substance use at baseline. In addition to the
      direct effects on pain, there were significant indirect effects of demographic
      and drug use variables on pain mediated through HIV/AIDS illness burden and prior
      pain. There were significant and positive indirect effects of current and past
      drug use, greater age, and lower SES on pain at all three time periods. Pain at 6
      months and pain at 12 months were also indirectly impacted by previous illness
      burden. Our results indicate that HIV+persons who screened positive for current
      use of a range of illicit substances experienced greater HIV/AIDS illness burden
      which in turn predicted increased pain.

PMID- 16297563
TI  - The pH-dependent conformational transition of beta-lactoglobulin modulates the
      binding of protoporphyrin IX.
AB  - We have investigated the interaction between PPIX and beta-lactoglobulin (beta
      lg) as a function of the pH of the solution. beta-lg is a small globular protein
      (MW approximately 18 kDa) with a very well characterized structure that reveals
      several possible binding sites for ligands. The interaction with beta-lg affects
      the photophysical properties of PPIX. The shift of PPIX emission maximum,
      excitation maximum and the increase of the fluorescence intensity is an indicator
      that binding between the porphyrin and beta-lg occurs. The binding constant
      appears to be modulated by the pH of the solution. Spectroscopic measurements do
      not reveal any significant energy transfer between the Trp residues of beta-lg
      and PPIX, however, fluorescence anisotropy decay measurements confirm the binding
      and the modulation introduced by the pH of the solution. Since beta-lg has been
      shown to be stable within the range of pH adopted in our experiments (5.0-9.0),
      the results suggest that PPIX binds a site affected by the pH of the solution.
      Because of the crystallographic evidence an obvious site is near the aperture of
      the interior beta-barrel however an alternative (or concurrent) binding site may
      still be present.

PMID- 16297564
TI  - Unambiguous representation of overlapping serial events in the rat hippocampal
      formation.
AB  - The hippocampal formation is suggested to be crucial in unambiguous
      representation of overlapping temporal sequences in episodic memory. We
      hypothesized that, if this was true, the hippocampal formation neurons would
      differentially respond to the same elements even in different temporal sequences.
      The present study was designed to investigate hippocampal formation CA1 neuronal
      activity of rats during performance of a conditional delayed stimulus-response
      association task in which three stimuli were conditionally and serially presented
      with a delay. In the task, the pairs of the second and third stimuli were
      overlapped across the trials, but separated by the preceding first stimuli.
      Conditioned tones coming from one of three possible directions were followed,
      after a short delay, by one of three pairs of reinforcement series. The pairs
      consisted of air puff (aversive sensory stimuli) and tube protrusion (which
      allowed licking sucrose behavior) in the following combinations: air puff-tube
      protrusion, tube protrusion-tube protrusion and tube protrusion-air puff. The
      pairs were interposed by a 2 s delay. The three conditioned tone directions were
      associated with these three pairs in a one-to-one correspondence, and its
      association was conditional to three possible conditioned tone frequencies (300,
      530, and 1,200 Hz). The responses of 107 neurons to the air puff and tube
      protrusion were analyzed by two-way ANOVA (task condition x reinforcement
      situation). Of 42 air puff-responsive and 64 tube protrusion-responsive neurons,
      36 and 53 displayed significant main effects and/or significant interaction,
      respectively. Furthermore, neural responses during the delay periods were
      dependent on the task conditions. The results indicated that the majority of the
      hippocampal formation neurons showed task condition- and/or reinforcement
      situation-dependent responses, suggesting a crucial role of the hippocampal
      formation in representation of overlapping serial events in episodic memory.

PMID- 16297565
TI  - Low-dose ouabain protects against excitotoxic apoptosis and up-regulates nuclear
      Bcl-2 in vivo.
AB  - Sodium-potassium ATPase (Na+,K+-ATPase) regulates the electrochemical gradient in
      cells, thereby providing fluid and ionic homeostasis. Additionally, interaction
      of the Na+,K+ pump with cardiac glycosides can activate intracellular signaling
      cascades (resulting in cell growth) and up-regulate transcription factors that
      promote cell survival. We used an in vivo excitotoxicity model to assess if
      Na+,K+-ATPase plays a role in neuronal apoptosis. After unilateral, intrastriatal
      injection of the glutamate receptor agonist kainic acid into postnatal day 7
      rats, Na+,K+ pump function was increased at 12 h after excitotoxic challenge, and
      levels of neuron-specific enzyme subunits were preserved (up to 24 h after
      injection) in membrane-enriched striatal fractions. In addition, co-injection of
      kainic acid with a low-dose (0.01 nmol) of the cardiac glycoside ouabain
      significantly (P<0.05) reduced striatal apoptosis (at 24 h post-injection)
      without diminishing Na+,K+-ATPase activity. To evaluate the possible mechanisms
      for this neuroprotection, we examined the levels of nuclear factor kappa B and
      Bcl-2 after cardiac glycoside exposure. Low-dose ouabain increased nuclear Bcl-2
      (but not nuclear factor kappa B) protein levels at 6 h post injection. Our
      results suggest that Na+,K+-ATPase allows for progression of apoptosis in
      excitotoxically-injured neurons, and that sublethal concentrations of ouabain
      provide neuroprotection against excitotoxicity. The mechanism for this ouabain
      neuroprotection could be intracellular cascades linked to the Na+,K+-ATPase
      ouabain interaction that modulate subcellular Bcl-2 levels. Targeted, therapeutic
      inhibition of apoptosis through cardiac glycosides may represent an effective
      strategy against excitotoxicity-mediated neuronal injury.

PMID- 16297566
TI  - Quantitative analysis of glutamate transporter mRNA expression in prefrontal and
      primary visual cortex in normal and schizophrenic brain.
AB  - Abnormalities of the glutamatergic system in schizophrenia have been identified
      in numerous studies, but little is known about the role of glutamate transporters
      and their messenger RNA (mRNA) expression. In addition, the abundances of the two
      major isoforms of human excitatory amino acid transporter 2 (EAAT2) or its rat
      ortholog, glutamate transporter 1, have never been compared in a quantitative
      manner. Using quantitative reverse transcription-polymerase chain reaction, we
      established that the expression of the EAAT1, EAAT2a, EAAT2b, and EAAT3
      transcripts was not different in the dorsolateral prefrontal and primary visual
      cortices of persons with schizophrenia relative to matched controls. EAAT2a
      expression was about 25-fold and 10-fold higher than EAAT2b in human and rat
      brain, respectively. The data provided no evidence of an effect of antipsychotic
      medications on the mRNA expression of the glutamate transporters. However,
      because most of the schizophrenic subjects in the cohort had been treated with
      antipsychotics for many years, it is still possible that changes in transporter
      expression were masked by medication effects.

PMID- 16297567
TI  - Rectal toxicity profile after transperineal interstitial permanent prostate
      brachytherapy: use of a comprehensive toxicity scoring system and identification
      of rectal dosimetric toxicity predictors.
AB  - PURPOSE: To better understand rectal toxicity after prostate brachytherapy, we
      employed the National Cancer Institute Common Terminology Criteria for Adverse
      Events (CTCAE version 3.0), a comprehensive system with distinct and separately
      reported gastrointestinal adverse event items (unlike Radiation Therapy Oncology
      Group morbidity scoring), to evaluate item-specific postimplant rectal
      toxicities. METHODS AND MATERIALS: We analyzed 135 patients treated with
      brachytherapy +/- hormonal therapy, using CTCAE v3.0 to score acute/late rectal
      toxicities (median follow-up, 41 months). Dosimetric parameters were evaluated
      for ability to predict toxicities. RESULTS: Use of CTCAE yielded a novel rectal
      toxicity profile consisting of diarrhea, incontinence, urgency, proctitis, pain,
      spasms, and hemorrhage event rates. No item had a < 5% Grade 1-2 acute toxicity
      rate (except spasms). Rectal dosimetry predicted late toxicities: for diarrhea,
      5% Grade 1 toxicity rate for %V25 (percent of rectal volume receiving 25% of
      prescribed prostate dose) < or = 25% vs. 60% for %V25 > 25% (p < 0.001); for
      maximum toxicity, 10% Grade 1 toxicity rate for %V10 < or = 40% vs. 44% for %V10
      > 40% (p = 0.007). CONCLUSIONS: A comprehensive understanding of item-specific
      postimplant rectal toxicities was obtained using CTCAE. Rectal %V25 > 25% and
      %V10 > 40% predicted worse late diarrhea and maximum toxicity, respectively.

PMID- 16297569
TI  - Overexpression of endoplasmic reticulum molecular chaperone GRP94 and GRP78 in
      human lung cancer tissues and its significance.
AB  - BACKGROUND: To investigate the relationship between the expression of glucose
      regulated protein94 (GRP94) and GRP78 at the level of mRNA and protein in vivo
      and in human lung cancer. METHODS: RT-PCR, real-time PCR, immunohistochemistry
      and/or Western blot were used in 54 cases of lung cancer and corresponding normal
      lung tissue. RESULTS: The expression pattern of GRP94 and GRP78 was similar.
      There was a significant overexpression of GRP94 and GRP78 at both mRNA and
      protein levels in cancer tissues as compared to normal tissues. The relative
      levels of GRP94 and GRP78 mRNA evaluated by RT-PCR in cancer and normal lung
      tissue were: GRP94: 3.48+/-2.06 versus 2.01+/-1.83; GRP78: 3.64+/-1.87 versus
      2.21+/-1.54; by real-time PCR were: GRP94: 2.89+/-0.64 versus 1.12+/-0.54; GRP78:
      2.56+/-0.82 versus 0.96+/-0.42. The relative level of GRP94 and GRP78 protein by
      Western blot in cancer and normal lung tissue were: GRP94: 3.46+/-1.72 versus
      1.81+/-0.92; GRP78: 4.84+/-2.55 versus 1.91+/-1.15, indicating an approximate 2
      fold and a 3-fold increase in GRP94 and GRP78 protein in cancer tissue as
      compared with normal tissue. Immunohistochemistry result for GRP94 and GRP78 in
      cancer and normal tissue was similar, that is: a stronger stain was observed in
      cancer tissue (main intensity of staining ++ to +++) compared to normal tissue
      (main intensity of staining + to ++). All the difference for GRP94 and GRP78
      between the two tissues were significant (p<0.05). Furthermore, the
      overexpression of GRP94 and GRP78 in the cancer tissue correlated with grade of
      differentiation and stage of tumors. There was stronger expression in poorly
      differentiated tumors than in well-moderately differentiated tumors (p<0.05).
      There was also stronger expression in stage III than in stages I and II tumors
      (p<0.05). No statistically significant differences were found among various
      pathologic types of tumors. Correlation analysis showed that there is a positive
      correlation between GRP94 and GRP78. CONCLUSION: The expression pattern of GRP94
      and GRP78 was similar in human lung cancer. They both were related with the
      differentiation and progression of the cancer. The expression at mRNA and protein
      level may be valuable in evaluating the grade of differentiation and clinical
      stage of human lung cancer.

PMID- 16297568
TI  - External audit of clinical practice and medical decision making in a new Asian
      oncology center: results and implications for both developing and developed
      nations.
AB  - PURPOSE: The external audit of oncologist clinical practice is increasingly
      important because of the incorporation of audits into national maintenance of
      certification (MOC) programs. However, there are few reports of external audits
      of oncology practice or decision making. Our institution (The Cancer Institute,
      Singapore) was asked to externally audit an oncology department in a developing
      Asian nation, providing a unique opportunity to explore the feasibility of such a
      process. METHODS AND MATERIALS: We audited 100 randomly selected patients
      simulated for radiotherapy in 2003, using a previously reported audit instrument
      assessing clinical documentation/quality assurance and medical decision making.
      RESULTS: Clinical documentation/quality assurance, decision making, and overall
      performance criteria were adequate 74.4%, 88.3%, and 80.2% of the time,
      respectively. Overall 52.0% of cases received suboptimal management. Multivariate
      analysis revealed palliative intent was associated with improved
      documentation/clinical quality assurance (p = 0.07), decision making (p = 0.007),
      overall performance (p = 0.003), and optimal treatment rates (p = 0.07); non
      small-cell lung cancer or central nervous system primary sites were associated
      with better decision making (p = 0.001), overall performance (p = 0.03), and
      optimal treatment rates (p = 0.002). CONCLUSIONS: Despite the poor results, the
      external audit had several benefits. It identified learning needs for future
      targeting, and the auditor provided facilitating feedback to address systematic
      errors identified. Our experience was also helpful in refining our national
      revalidation audit instrument. The feasibility of the external audit supports the
      consideration of including audit in national MOC programs.

PMID- 16297570
TI  - Characterisation of a new splice variant of MASK-BP3(ARF) and MASK human genes,
      and their expression patterns during haematopoietic cell differentiation.
AB  - In this study we report the characterisation of a new splice variant, here
      denominated splice variant 4 (accession number AF258557) of the human Multiple
      Ankyrin repeats Single KH domain (hMASK) (accession number AF521882) and the
      hMASK-4E-Binding Protein 3 Alternative Reading Frame (hMASK-BP3(ARF)) (accession
      number AF521883), containing a number of ANK-repeat motifs. Ankyrin (ANK) repeat
      containing proteins carry out a wide variety of biological activities and are
      involved in processes, such as cell differentiation and transcriptional
      regulation. The present study reports the computer analysis of these splice
      variant cDNAs and their broad mRNA expression in different normal human tissues
      and cancer cell lines. An upregulation of the splice variant mRNAs expression was
      observed after HL-60 and erythroblast differentiation. The upregulation of splice
      variant 4 mRNA was considerably higher than those of the other variants, during
      erythroid differentiation.

PMID- 16297571
TI  - Molecular and evolutionary characterization of the GnRH-II gene in the chicken:
      distinctive genomic organization, expression pattern, and precursor sequence.
AB  - Of all the structural variants of GnRH (gonadotropin-releasing hormone), GnRH-II
      has been found to be universally present in and uniquely conserved among jawed
      vertebrates without any sequence substitutions. Our previous study found that the
      GnRH-II precursor sequences have become divergent in the lineage of eutherian
      mammals, based on a comparison between reptilian and mammalian GnRH-II. To
      elucidate the molecular evolution of GnRH-II throughout amniotes, we have
      performed the first identification of the avian GnRH-II cDNA/gene from the
      chicken, the species used for the initial discovery of GnRH-II peptide. Gene
      arrangement around the GnRH-II in the chicken was similar to that in mammals;
      however, a gene MRPS26 was partly overlapped with the downstream part of the GnRH
      II in the chicken. It was identified that the GnRH-II/MRPS26 locus generated at
      least five distinct types of transcripts with different expression patterns and
      three of them may produce functional GnRH-II decapeptide. Sequence comparison
      revealed that the prepro-GnRH-II polypeptide of the chicken was substantially
      different from those of other species regarding the length and similarity. The
      present results strongly indicated that considerable variations were generated in
      the precursor sequence of the evolutionarily conserved GnRH-II during amniote
      evolution. It was also suggested that the sequence divergence seen in the chicken
      may have occurred independently of that in the mammalian lineage.

PMID- 16297572
TI  - Novel splice variants of human ADAR2 mRNA: skipping of the exon encoding the
      dsRNA-binding domains, and multiple C-terminal splice sites.
AB  - We report here two previously unknown alternative splice sites in the mRNA of
      human adenosine deaminase acting on RNA type 2 (ADAR2), an RNA editing enzyme.
      One splices out the whole of exon 2, which encodes two double-stranded RNA
      binding domains (dsRBDs), resulting in a frameshift that introduces a stop codon
      in the downstream exon. This variant accounts for between 13% and 20% of the
      total ADAR2 mRNA in each developmental stage and brain region examined, even
      though its translated product is not expressed at levels that are detectable by
      Western blot analysis. The other new splice site is located in exon 9, 83
      nucleotides downstream of the stop codon for the long C-terminus, resulting in a
      new 3' untranslated region (UTR) that is about 80 bp longer than the previously
      reported short C-terminus. The variant produced by this splice site has a stop
      codon at the same site as that in ADAR2 mRNA containing canonical exons 9 and 10,
      and is predicted to be translated as an enzymatically active ADAR2 protein. With
      these two additional splice sites, a total of 48 mRNA variants are theoretically
      possible, because each splicing event occurs independently. Among them, variants
      containing the long C-terminus are translated in human brains in situ, implying
      that alternative splicing in the 3' UTR of ADAR2 might regulate translational
      efficiency and mRNA stability in vivo.

PMID- 16297573
TI  - Molecular cloning, characterization and localization of chicken type II
      procollagen gene.
AB  - Chicken type II procollagen (ccol2a1) has become as an important oral tolerance
      protein for effective treatment of rheumatoid arthritis. However, its molecular
      identity remains unclear. Here, we reported the full-length cDNA and nearly
      complete genomic DNA encoding ccol2a1. We have determined the structural
      organization, evolutional characters, developmental expression and chromosomal
      mapping of the gene. The full-length cDNA sequence spans 4837 bp containing all
      the coding region of the ccol2a1 including 3' and 5' untranslation region. The
      deduced peptide of ccol2a1, composed of 1420 amino acids, can be divided into
      signal peptide, N-propeptide, N-telopeptide, triple helix, C-telopeptide and C
      propeptide. The ccol2a1 genomic DNA sequence was determined to be 12,523 bp long
      containing 54 exons interrupted by 53 introns. Comparison of the ccol2a1 with its
      counterparts in human, mouse, canine, horse, rat, frog and newt revealed highly
      conserved sequence in the triple helix domain. Chromosomal mapping of ccol2a1
      locates it on 4P2. While the ccol2a1 mRNA was expressed in multiple tissues, the
      protein was only detected in chondrogenic cartilage, vitreous body and cornea.
      The ccol2a1 was found to contain two isoforms detected by RT-PCR. The
      distribution of the ccol2a1 lacking exon 2wasfrequently detected in chondrogenic
      tissues, whereas the exon 2-containing isoform was more abundant in non
      chondrogenic tissues. These results provide useful information for preparing
      recombinant chicken type II collagen and for a better understanding of normal
      cartilage development.

PMID- 16297574
TI  - Independent expansion of the keratin gene family in teleostean fish and mammals:
      an insight from phylogenetic analysis and radiation hybrid mapping of keratin
      genes in zebrafish.
AB  - The sequence and chromosomal distribution of keratin genes of zebrafish were
      compared with that of other fishes and mammals to provide an insight into the
      evolution of this gene family in vertebrates. By comparative sequence analysis
      and radiation hybrid mapping, we identified 16 type I and 7 type II keratin genes
      in the zebrafish genome. This contrasts with mammals, where type I and type II
      keratin genes are similar in number. The keratin genes are scattered in the fish
      genome, contrasting with the two clusters of keratin genes in mammalian genomes.
      Compared to genes from two species of pufferfish, the zebrafish type I keratin
      genes underwent an expansion by independent tandem duplications. Expression
      profiles based on EST counts suggest that some of the tandemly duplicated type I
      keratin genes from zebrafish either underwent sub-functionalization or acquired
      new expression domains. The chromosomal arrangement of keratins 8, keratin18, and
      a second type II keratin, as a cluster of three genes, has remained conserved in
      vertebrate evolution, except for duplication of the three-gene cluster in some
      teleosts. This contrasts with other members of the keratin gene family, which
      diverged independently between fish and mammals.

PMID- 16297575
TI  - Analysis of the matrix protein gene sequence of the Asian lineage of peste-des
      petits ruminants vaccine virus.
AB  - The M gene nucleotide sequence of an Indian peste-des-petits ruminants (PPRV)
      vaccine virus ("PPRV Sungri/96") belonging to Asian lineage was determined. The
      gene is 1476 nucleotides long with a single open reading frame (ORF). The
      nucleotide and predicted amino acid sequence was compared with the homologous
      region of the African Lineage Vaccine virus "PPRV/Nigeria/75/1". The nucleotide
      sequence of the "PPRV Sungri/96" was 86% identical to that of
      "PPRV/Nigeria/75/1", while a homology of 93% and 95% could be observed in the ORF
      and amino acids level, respectively. The M gene encodes a protein of 335 amino
      acids, with a predicted molecular weight (MW) of 37.8 kDa. The ORF is flanked by
      a 3' untranslated region of 436 nucleotides and a high level of sequence
      divergence (approximately 30%) could be observed in this region between the
      vaccine viruses of Asian and African lineages. A high degree of conservation of
      several amino acids of this protein observed previously was also confirmed in
      this study.

PMID- 16297576
TI  - The effect of a soy-rich diet on urogenital atrophy: a randomized, cross-over
      trial.
AB  - OBJECTIVE: To evaluate the effect of a soy-rich diet on urogenital symptoms,
      vaginal health index, and vaginal cytology in perimenopausal and postmenopausal
      women. MATERIALS AND METHODS: Thirty-six perimenopausal and postmenopausal women
      (mean age 52.5+/-5.1 years) participated in a randomized, cross-over trial with
      two 12-week diet periods and two 4-week washout periods before and between
      treatments. The study diet consisted of a control diet (soy-free diet) and an
      isocaloric soy-rich diet (25 g soy protein in various forms of soy food
      containing more than 50 mg/day of isoflavones substituted for an equivalent
      amount of animal protein). Subjects were assessed for urogenital symptoms,
      vaginal health index, vaginal pH and vaginal cytology. The single physician and
      the single cytopathologist were blinded with regard to onset, period and
      randomization number. Statistical analyses were performed using paired t-test or
      Wilcoxon Signed Ranks Test, significance was set as P<0.05. RESULTS: Good
      compliance to the diet was shown by the significant elevation of serum levels of
      daidzein and genistein during the soy-rich diet period. The symptoms of urge
      incontinence and vaginal dryness had significantly increased after 12-week of soy
      free diet. All other urogenital symptoms did not change in both periods. The
      vaginal health index, the vaginal pH, the karyopyknotic index, and the maturation
      value were not significantly changed in both periods. CONCLUSION: A soy-rich diet
      did not relieve the urogenital symptoms or restore the vaginal epithelium or
      improve the vaginal health in perimenopausal and postmenopausal Thai women.

PMID- 16297577
TI  - Medical resource utilisation and cost of care for women seeking treatment for
      urinary incontinence in an outpatient setting. Examples from three countries
      participating in the PURE study.
AB  - OBJECTIVE: To describe the medical resource use and direct costs of treatment for
      women with urinary incontinence (UI) in European countries. DESIGN: PURE is a non
      interventional, observational study of patients seeking treatment for UI in an
      outpatient setting. SETTING: Investigators being either general practitioners
      (GPs) and/or specialists, i.e. urologists and gynaecologists, in 14 European
      countries participated in PURE. The results for medical resource use and cost of
      treatment in Germany, Spain and the UK/Ireland recorded retrospectively at the
      enrolment visit for the preceding 12 months are presented here. SUBJECTS:
      Treatment-seeking women aged over 18 years who were under treatment or seeking
      treatment for UI, and who presented within the normal course of care for UI were
      enrolled in the 6 months study. MEASUREMENTS: Information on the incontinence
      resource use was gathered on standard data collection forms. The direct medical
      costs were calculated by attaching the unit costs from the perspective of the
      relevant health insurance in each country to the country-specific resource use.
      Furthermore, the contribution of patients to the costs of pads, or any treatment
      for UI was assessed. RESULTS: Variation in medical resource use and cost of
      treatment between the three countries was observed, reflective of the differences
      in the healthcare systems and whether specialists and/or GPs provided the care.
      We found that women in Spain and Germany are more likely to have consulted a
      specialist for their UI symptoms, which had implications for utilisation of
      diagnostic procedures. Conservative treatment, particularly pelvis floor muscle
      exercises, was more common in patients in the UK/Ireland treated in primary care
      by GPs. In all three countries most of the women had used protective pads, which
      more than half the patients paying for them out-of-pocket, despite potential
      healthcare reimbursement schemes. Mean total UI-related costs per year ranged
      from 359 in the UK/Ireland for patients predominantly treated in the GP setting
      to 515 in Germany and 655 in Spain for patients treated by specialists and GPs.
      CONCLUSIONS: Our study provides an estimation of resource use and costs
      associated with UI in treatment-seeking European women, exemplified here in three
      countries.

PMID- 16297578
TI  - A description of health care provision and access to treatment for women with
      urinary incontinence in Europe -- a five-country comparison.
AB  - BACKGROUND: Female urinary incontinence is a prevalent condition, but only about
      one-third of women seek treatment. OBJECTIVES: To describe the health care
      provision for women with urinary incontinence from a European perspective,
      selecting France, Germany, Spain, Sweden, and the United Kingdom as examples, and
      to investigate whether specific barriers for treatment exist. METHODS: Available
      health care system information, a literature review and clinical expert
      information identified patterns of treatment provision. RESULTS: In Spain,
      Sweden, and the UK, access to medical care in general is primarily through the
      general practitioners. However, in Spain and Sweden, women with urinary
      incontinence can directly visit specialists. In France and Germany, women have
      equal access to either general practitioners or specialists. Aside from general
      practitioners, gynaecologists play a major role in urinary incontinence care in
      all countries except the UK. In Germany, urologists are also involved in initial
      female urinary incontinence care; however, only in about 16% of women. There are
      no waiting lists in France and Germany for appointments with physicians or
      procedures, contrary to Spain, which has long waiting lists. Access to general
      practitioners in the UK is unrestricted whereas advanced diagnosis and treatment
      in secondary care requires long waits. A specific Swedish policy mandates that no
      woman is required to wait longer than 3 months for incontinence visits and
      related surgery. In Sweden and the UK, specialist nurses and other health care
      workers provide incontinence services. Almost all treatment options for urinary
      incontinence are at least in part reimbursed. However, various co-payments and
      fees in France, Germany, Spain and Sweden exist and constitute out-of-pocket
      expenses for women if no complementary additional private health insurance is
      available. In some countries, financial incentives for physicians to provide
      incontinence services are low, raising concerns about their interest to engage in
      continued patient care. CONCLUSIONS: Information about service provision in
      Europe for women with urinary incontinence is limited and makes it difficult to
      understand barriers to treatment seeking. A broad European perspective may
      promote optimised treatment access in the future for this widespread and under
      recognised condition.

PMID- 16297579
TI  - Patient-reported impact of urinary incontinence--results from treatment seeking
      women in 14 European countries.
AB  - OBJECTIVES: To describe the patient-reported impact of urinary incontinence (UI)
      in treatment-seeking women in Europe. DESIGN: PURE was a non-interventional,
      observational study, which aimed to describe the direct costs of treatment for
      European women seeking treatment for UI. A secondary study objective was to
      describe the impact of UI on health-related quality of life (HRQoL) by UI subtype
      and severity of disease. This paper presents the results from quality of life
      assessments as well as bothersomeness and interference with daily activities from
      the first study observation. SUBJECTS: Nine thousand four hundred and eighty
      seven European women who had UI symptoms in the last 12 months were enrolled.
      Their UI symptoms were frequently those defined as mixed urinary incontinence
      (MUI) and were moderate to severe in nature. MEASUREMENTS: HRQoL was assessed at
      the first observation using the urinary Incontinence-specific Quality of Life
      Questionnaire (I-QOL) and the EQ-5D, a generic quality of life questionnaire.
      Data collected from EQ-5D provided insight into the patients' general health
      perception, while the I-QOL data indicated how affected the women were about
      their UI symptoms. Higher EQ-5D and I-QOL scores represent better quality of
      life. Patients were asked to indicate how much UI symptoms limited selected
      activities and to indicate the degree to which they found their symptoms to be
      bothersome. RESULTS: Overall, the median self-rated health status on the EQ-5D
      visual analogue scale (VAS) was 70.0 and the median EQ-5D health state index was
      0.85, with small but noticeable differences observed between countries. Of the
      five health dimensions of the EQ-5D, patients' self-care appeared to be the least
      affected by UI, with fewer than 10% of the women reporting that they had some
      problems. Between 20 and 40% of patients had some problems with their mobility
      and usual activities, or had pain/discomfort or anxiety/depression. However, the
      impact of existing co-morbidity was not assessed and may have affected some
      women's scoring of the EQ-5D domains. The mean total I-QOL score overall was 57.7
      and of the three subscales of the I-QOL, psychosocial impact had the highest
      overall scores, representing fewer problems, with lower scores observed for the
      avoidance and limiting behaviour subscale, and even lower scores for the social
      embarrassment subscale. The greatest patient-reported impact of UI symptoms on
      activities was on exercise, with more than 45% of patients moderately to totally
      limited in this activity. In most of the countries, more than 60% of the women
      reported that they were moderately to extremely bothered by their UI symptoms.
      CONCLUSIONS: There was considerable impact of UI on HRQoL in a treatment seeking
      population, as demonstrated by the disease-specific quality of life scale and by
      the high percentage of patients who were bothered by their symptoms.

PMID- 16297580
TI  - Characteristics of female outpatients with urinary incontinence participating in
      a 6-month observational study in 14 European countries.
AB  - OBJECTIVE: To describe the characteristics of women seeking treatment for
      symptoms of urinary incontinence (UI) in European countries. DESIGN: Prospective
      urinary incontinence research (PURE) was a 6-month, observational, pan-European
      study, primarily aimed at determining the direct costs of urinary incontinence
      treatment. The secondary objectives of PURE were to describe the impact of UI on
      health-related quality of life (HRQoL) in treatment seeking patients and to
      illustrate the treatment patterns for UI in Europe. SETTING: One thousand and
      Fifty-five physicians from 14 European countries, including general practitioners
      (GPs), gynaecologists, urologists and geriatricians, observed women seeking
      treatment for their UI and recorded data at the first observation and then
      prospectively at 3 and 6 months after the first observation during the normal
      course of therapy. SUBJECTS: Women of at least 18 years of age who had
      experienced urinary leakage in the 12 months prior to enrolment in the study, who
      were seeking treatment or under treatment for UI and who presented within the
      normal course of UI care were included in the 6 months study. The first
      observation characteristics of the patients are described here. METHODS:
      Demographic characteristics, as well as disease and treatment status at first
      observation were explored using descriptive summary statistics to gain an
      understanding of the population studied. RESULTS: In total, 9487 women took part
      in PURE, with the largest patient groups from Germany, Spain and the UK/Ireland.
      The majority of women were post-menopausal and had a mean age of 60.7 years, were
      not current smokers and tended to be overweight (BMI > 25.0). Overall, mixed UI
      symptoms were more common than SUI and UUI, as defined by clinical opinion (SUI
      38%, MUI 42% and UUI 18%), and by a two-item questionnaire, the S/UIQ (SUI 29%,
      MUI 58% and UUI 13%). Around half of the patients (48%) suffered from their
      symptoms for less than 2 years before consulting a physician; 28% delayed seeking
      treatment for 3-5 years, with 13% waiting for 6-10 years and the remaining 11%
      waiting for 11 or more years. CONCLUSIONS: Some of the described patients'
      characteristics may provide important information to clinicians to enable them to
      take a more active approach to case-finding, which will ultimately benefit the
      incontinent patient.

PMID- 16297582
TI  - Epidermal cell culture model with tight stratum corneum as a tool for dermal gene
      delivery studies.
AB  - The purpose of this study was to evaluate the feasibility of organotypic cultures
      of rat epidermal cells as a tool to study non-invasive dermal gene delivery.
      Also, a novel transfection method employing liposomal pre-treatment of stratum
      corneum (SC) was evaluated. Rat epidermal cells were cultured on Transwell tissue
      culture inserts and formation of stratum corneum barrier was evaluated in
      permeability studies with two model compounds. Transfections were performed with
      naked pCMV-SEAP2 plasmid and 1,2-dioleoyl-3-trimethylammonium-propane
      (DOTAP)/dioleyl-phosphatidylethanolamine (DOPE)/DNA lipoplexes. Naked DNA was
      administered on the stratum corneum of the cell culture model with or without
      prior treatment of the stratum corneum with DOTAP/DOPE liposomes. Transfection
      was evaluated non-invasively by monitoring concentrations of secreted alkaline
      phosphatase (SEAP) in the culture medium of the basolateral compartment at 24-h
      intervals. Transfection with lipoplexes produced significant gene expression in
      rat epidermal keratinocyte (REK) epidermal culture model. Likewise, delivery of
      naked DNA on stratum corneum after DOTAP/DOPE liposome pre-treatment produced
      gene expression. Naked DNA alone did not result in detectable gene expression. In
      dermal gene delivery studies REK epidermal culture model is a suitable tool that
      includes tight stratum corneum and allows transgene expression in viable
      epidermis and non-invasive sampling of secreted gene product in the basolateral
      compartment. Liposomal pre-treatment of the stratum corneum augments transfection
      of viable epidermis.

PMID- 16297581
TI  - Rheological, adhesive and release characterisation of semisolid
      Carbopol/tetraglycol systems.
AB  - Gels dosage forms are successfully used as drug delivery systems considering
      their ability to control drug release and to protect medicaments from an hostile
      environment. This study deals with the gelation properties of Carbopol 971 e 974
      polymeric systems in tetraglycol, a water-miscible cosolvent. In this paper, the
      attention was noted of the thickening properties of the different Carbopol in
      tetraglycol solvent at increasing temperatures, in order to obtain gels avoiding
      neutralisation and, at the same time, to make possible the dissolution in these
      gels of insoluble or poorly soluble water drugs. Samples were prepared by simply
      dispersing different Carbopols amount (0.5-4%) were added to tetraglycol and
      different systems were prepared at room temperature and by heating at 70 degrees
      C. All these systems were then characterised rheologically. Frequency sweep,
      creep-recovery, temperature sweep and time sweep analyses outlined that Carbopol
      971 and 974 in tetraglycol gave rise after heating to gels with satisfactory
      rheological behaviour: the elastic modulus was greater than the viscous one and a
      remarkable elastic character was found to be present. Systems obtained by heating
      procedure were examined also from a mechanical point of view using a texture
      profile analysis. Besides, being Carbopols well known mucoadhesive polymers, gels
      adhesive properties were also studied using the ex vivo method. Texture and
      adhesion characterisation confirmed rheological results pointing out a certain
      greater elasticity and adhesiveness of Carbopol 974 systems. Then, the possible
      cutaneous irritation was also tested using the in vivo method (Draize test). No
      signs of cutaneous irritation were obtained for all the samples that were
      analysed. After rheological and mucoadhesive properties were set, paracetamol as
      a model drug was inserted in the composition of the gels and the release
      characteristics were defined. Dissolution tests pointed out the greater release
      control properties of tetraglycol/Carbopol 971 samples. These studies showed
      tetraglycol/Carbopol systems as a first-rate alternative to traditional water
      gels when low water-soluble drugs have to be added.

PMID- 16297583
TI  - Morphine, haloperidol and hyoscine N-butyl bromide combined in s.c. infusion
      solutions: compatibility and stability. Evaluation in terminal oncology patients.
AB  - The administration of drugs by subcutaneous infusion is routinely practiced in
      palliative medicine for the management of patients who are no longer able to take
      oral medication. It is common for two or more drugs to be combined in
      subcutaneous solutions. The combination of an opioid with other drugs (haloperiol
      lactate and hyoscine N-butyl bromide) can be very valuable. Unfortunately, the
      compatibility and stability of morphine hydrochloride, haloperidol lactate and
      hyoscine N-butyl bromide combined in the same solution has not yet been
      determined. Therefore, this study examined the stability of ternary solutions
      containing morphine HCl, haloperidol lactate and hyoscine N-butyl bromide at
      different dose ranges. Twelve different solutions were assessed for 15 days after
      preparation in polypropylene syringes using 0.9% saline as diluent. Triplicate
      syringes were stored at 25 degrees C. HPLC was the analytical technique used to
      measure morphine HCl, haloperidol lactate and hyoscine N-butyl bromide. Initial
      concentration ranges were 1.67-10.0 mg/ml for morphine HCl, 0.417-0.625 mg/ml for
      haloperidol lactate and, 5.0-6.67 mg/ml for hyoscine N-butyl bromide. All three
      drugs were very stable (>92.5%) when stored at 25 degrees C. The clinical
      performance of the admixture was retrospectively assessed in 21 terminal oncology
      patients. Total symptom control was achieved in 17 out of 21 patients with very
      good local tolerance.

PMID- 16297584
TI  - Plants used by the Cree Nation of Eeyou Istchee (Quebec, Canada) for the
      treatment of diabetes: A novel approach in quantitative ethnobotany.
AB  - In the last decade, the Cree Nation of Eeyou Istchee has witnessed a 150%
      increase in the prevalence of Type II Diabetes (T2D) for people aged over 20
      years. Clinical intervention using conventional therapeutic methods has yielded
      only a limited success within this population. An ethnobotanical survey was
      carried out to identify potentially antidiabetic plant species used within the
      traditional pharmacopoeia of the Cree. Interviews were held with 34 Cree Elders
      using a list of 15 symptoms ranked according to their association to T2D. A total
      of 18 species were cited during the survey, spanning 9 plant families. Species
      were prioritized for pharmacological analysis according to a Syndromic Importance
      Value, based on their frequency of citation by informants and the number and
      specificity of symptoms for which they were used. Correspondence and clustering
      analyses were also performed to determine the specificity of association between
      species and symptoms and the symptom-based correlation between species. A data
      matrix and species ranking order generated from Cree-specific literature
      demonstrates significant similarity and correlation to our original matrix and
      ranking, respectively. This article demonstrates the applicability of various
      underutilized quantitative tools in ethnobotany, while taking a convincing
      preliminary step towards a therapy more in harmony with Cree culture and
      lifestyle.

PMID- 16297585
TI  - [Linezolid, the first oxazolidinone antibiotic].
AB  - The spread of multiresistant Staphylococcus and Enterococcus strains required the
      development of new drugs. Linezolid is the first molecule of a new antibiotic
      family, oxazolidinones, with an original mechanism of action. In this general
      review, the authors first present its antibacterial activity, its pharmacokinetic
      properties, its therapeutic uses in serious Gram-positive infections, pneumonia,
      skin and soft tissue infections, and also in other indications. They then explain
      the rules for administration and tolerability.

PMID- 16297586
TI  - Age-specific and lifetime behavior patterns in Drosophila melanogaster and the
      Mediterranean fruit fly, Ceratitis capitata.
AB  - Patterns of behavior were recorded every 10 min during a 2-h period each day from
      eclosion to death for individual Drosophila melanogaster (both sexes) and
      Ceratitis capitata (males-only) including walking, preening, feeding, flying, and
      resting for the former species, and walking, calling (signaling), supine (upside
      down), and resting in the latter. Results reveal that, with the exception of
      preening in D. melanogaster, behavioral patterns are age-specific and the
      frequency of several behaviors (e.g. supine in medfly; walking and resting in D.
      melanogaster) are correlated with time-to-death. This is the first set of studies
      to report the age patterns over a range of behavioral categories throughout the
      lives of individuals and thus the first that systematically documents the
      behavior of individuals at advanced ages. We suggest that the new and unique
      behaviors (e.g. supine) that emerge from the aging process be referred to as
      degenerative behaviors, not only to distinguish them from the conventional
      behavioral classifications (innate, learned), but also to reflect their emergent
      nature.

PMID- 16297587
TI  - Interleukin-1beta and interleukin-6 gene polymorphisms as risk factors for AD: a
      prospective study.
AB  - Risk of incident dementia from any cause and Alzheimer's disease (AD) in relation
      to the IL-1beta-511 (C-->T) and IL-6-174 (G-->C) polymorphisms was investigated
      in an Italian elderly cohort (n=791) with 4 years of follow-up. Analyses were
      adjusted for socio-demographic confounders (age, gender, education), presence of
      the Apolipoprotein E-epsilon4 allele, and plasma total homocysteine (tHcy), a
      newly proposed AD risk factor. No significant association was found for the IL
      1beta-511 and IL-6-174 polymorphisms with either dementia or AD. However, in the
      baseline dementia-free cohort considered as a whole, independently of other
      confounders, IL-1beta-511 T/T homozygotes had lower plasma tHcy than both
      heterozygotes (P=0.036) and wild-types (P=0.004). These data do not support the
      hypothesis that the IL-1-beta-511 and IL-6-174 polymorphisms affect dementia or
      AD risk. The relationship between the AD risk factor plasma tHcy and the IL-1beta
      511 polymorphism was never reported before and might explain previous cross
      sectional reports of an association between this polymorphism and AD.

PMID- 16297588
TI  - Micellar electrokinetic chromatography for separation of a mixture of coptis
      alkaloids, scute flavonoids, and rhubarb anthraquinones and bianthrones.
AB  - Coptidis Rhizoma, Scutellariae Radix, and Rhei Rhizoma are three common Chinese
      herbs. There are many herbal formulas which contain either two or all three of
      the herbs mentioned above. Their bioactive components have already been
      identified, respectively. However, there is no report about separation of the 13
      bioactive constituents of the three herbs at the same time. In order to assess
      these constituents of related Chinese herbal preparations, a micellar
      electrokinetic chromatography method was developed. While buffer pH and
      surfactant concentration affected the resolution of separation, acetonitrile
      percentage was found to significantly influence the resolution, peak shape, and
      elution window. Optimum separation of 13 compounds was achieved at pH 7.3 using a
      buffer mixture of 70% (v/v) 3 mM di-sodium tetraborate, 10 mM sodium dihydrogen
      phosphate, and 50 mM sodium deoxycholate with 30% (v/v) acetonitrile. When
      applying the developed method to analyze a model preparation, San-huang-xie-xin
      tang, which contains all three herbs, 8 of the 13 bioactive constituents, could
      be determined. The present study proposed a method to assess San-huang-xie-xin
      tang within short analysis time and also provided a possible starting point to
      evaluate related herbal preparations containing Coptidis Rhizoma, Scutellariae
      Radix, and Rhei Rhizoma.

PMID- 16297589
TI  - Simultaneous determination of triamcinolone acetonide and oxymetazoline
      hydrochloride in nasal spray formulations by HPLC.
AB  - A high-performance liquid chromatography (HPLC) method with UV detection at 232
      nm was developed and validated for the simultaneous determination of
      triamcinolone acetonide (TAA) and oxymetazoline hydrochloride (OXY) in nasal
      spray formulations. The chromatographic system consisted of a micro Bondapak CN
      column (150 mm x 3.9 mm), 5 microm particle size with a mobile phase composition
      of acetonitrile:ammonium acetate (pH 5.0, 20mM) (10:90, v/v) at a flow rate of
      1.0 mL/min. Calibration curves were linear for both TAA and OXY in the
      concentration range of 2.5-25.0 microg/mL. The limit of detection and
      quantitation were 0.29 and 0.88 microg/mL for OXY and 0.24 and 0.73 microg/mL for
      TAA. The described method was further applied to the analysis and stability
      studies of two nasal spray formulations I and II prepared from TAA and OXY
      commercial nasal spray products. The stability of OXY and TAA in the commercial
      products and the nasal formulations I and II were analyzed after 30 days at room
      temperature and 30 days at 40 degrees C/60% relative humidity. The results of the
      stability study showed that OXY and TAA in the commercial nasal spray products
      and the nasal formulations I and II were stable at 20-25 degrees C (room
      temperature) but TAA was unstable at 40 degrees C/60% relative humidity. TAA
      exhibited more than 10% loss at 14 days in both the nasal formulations and in the
      commercial products. OXY showed increased degradation at 40 degrees C/60%
      relative humidity but <10%.

PMID- 16297590
TI  - Determination of DPPH free radical scavenging activity by reversed-phase HPLC: a
      sensitive screening method for polyherbal formulations.
AB  - The colorimetric method of evaluation of antioxidant activity by scavenging 1,1
      diphenyl-2-picrylhydrazyl (DPPH) free radical is with certain shortcomings like
      failure to indicate antioxidant activity of certain drugs and interference from
      color pigments of natural products. A specific HPLC method was developed for
      evaluating the DPPH free radical scavenging activity of commercial polyherbal
      formulations using a LiChrospher 100 RP-18e column (250 mm x 4 mm, 5 microM). The
      mobile phase was a mixture of methanol and water (80:20, v/v) pumped at a flow
      rate of 1 mL/min. The DPPH peaks were monitored at 517 nm. The method was
      standardized using known antioxidants such as ascorbic acid, 6-hydroxy-2,5,7,8
      tetramethylchroman-2-carboxylic acid (trolox), probucol and alpha-tocopherol. The
      50% radical scavenging activity (IC50) determined by the HPLC method correlated
      well with that of colorimetry. This HPLC method was applied for the estimation of
      free radical scavenging activity of Silymarin and a few commercial
      hepatoprotective polyherbal formulations. While the colorimetric method failed to
      estimate the free radical scavenging activity of polyherbal formulations, HPLC
      method was free from interferences and was specific. The HPLC method is sensitive
      and can be used as a quality control tool for the rapid determination of free
      radical scavenging activity of variety of products including plant extracts,
      foods, drugs and polyherbal formulations.

PMID- 16297591
TI  - Prognostic factors in non-small cell lung cancer surgery.
AB  - AIMS: Complete surgical resection of primary tumours remains the treatment with
      the greatest likelihood for survival in early-stage non-small cell lung cancer
      (NSCLC). Although TNM stage is the most important prognostic parameter in NSCLC,
      additional parameters are required to explain the large variability in
      postoperative outcome. The present review aims at providing an overview of the
      currently known prognostic markers for postoperative outcome. METHODS: We
      performed an electronic literature search on the MEDLINE database to identify
      relevant studies describing the risk factors in NSCLC surgery. The references
      reported in all the identified studies were used for completion of the literature
      search. RESULTS: Poor pulmonary function, cardiovascular disease, male gender,
      advanced age, TNM stage, non-squamous cell histology, pneumonectomy, low hospital
      volume and little experience of the surgeon were identified as risk factors for
      postoperative outcome. However, with the exception of TNM stage and extent of
      resection, the literature demonstrates conflicting results on the prognostic
      power of most factors. The role of molecular biological factors, neoadjuvant
      treatment and adjuvant treatment is not well investigated yet. CONCLUSIONS: The
      advantage of knowing about the existence of comorbidity and prognostic risk
      factors may provide the clinician with the ability to identify poor prognostic
      patients and establish the most appropriate treatment strategy. The assessment of
      prognostic factors remains an area of active investigation and a promising field
      of research in optimising therapy of NSCLC patients.

PMID- 16297592
TI  - [Paravertebral block].

PMID- 16297593
TI  - Cu-Zn super oxide dismutase as a potential antifibrotic drug for hepatitis C
      related fibrosis.
AB  - Liver fibrosis plays a pivotal role in liver function impairment and is a feature
      of chronic infection by hepatitis C virus (HCV). Ten to 20% of patients progress
      to cirrhosis leading to an increased risk of liver failure or hepatocellular
      carcinoma (HCC). Recent advances have culminated in clear evidence that fibrosis
      can be reversible, and in expectation that effective anti-fibrotic therapy will
      improve the prognosis. Among the different cellular pathways involved in
      fibrosis, the transforming growth factor-beta1 (TGF-beta1) signaling plays a
      major role. Increases of TGF-beta1 expression is associated with fibrotic
      diseases and this cytokine could be a target for an antifibrotic drug. Clinical
      results on radiation-induced fibrosis have brought some evidences that Cu-Zn SOD
      (SOD1) could be an anti-fibrotic drug. Its therapeutic effect could be related to
      a down-regulation of TGF-beta1 as proved in a well characterized pig model of
      radiation induced fibrosis, where the efficacy of Cu-Zn SOD has been shown in
      reversing fibrosis. Using 3-D skin co-culture of fibroblasts from this pig model,
      it was showed that SOD significantly reduces the expression of the TGFbeta1, both
      at the mRNA and protein level. An experimental work could be undertaken to
      validate the Cu-Zn SOD as an anti-fibrotic drug, using HCV core protein
      expressing transgenic mice. As the current anti-HCV therapy with pegylated
      interferon combined with ribavirin can eradicate virus and stop the progression
      of fibrosis, but near 50% of HCV infected patients are non responders, a
      controlled trial is planned for HCV infected patients non responders to this
      therapy with a Metavir fibrosis score reaching F = 2 or >2.

PMID- 16297594
TI  - In vitro cytotoxicity of a theaflavin mixture from black tea to malignant,
      immortalized, and normal cells from the human oral cavity.
AB  - The growth inhibitory effects of a theaflavin mixture from black tea were more
      pronounced to malignant (CAL27; HSC-2; HSG1) and immortalized (S-G; GT1) cells
      than to normal (HGF-2) cells from the human oral cavity. Studies with malignant
      carcinoma CAL27 cells and immortalized GT1 fibroblasts showed that cytotoxicity
      of the theaflavin mixture was enhanced as the exposure time was increased, with
      the tumor CAL27 cells more sensitive than the GT1 cells. Hydrogen peroxide
      (H(2)O(2)) was detected in cell culture medium amended with the theaflavin
      mixture. The level of H(2)O(2) in cell culture medium amended with the theaflavin
      mixture was lessened in the presence of catalase and CoCl(2); the level of
      authentic H(2)O(2) was also lessened in the presence of CoCl(2), suggesting that
      Co(2+) led to the rapid catalytic decomposition of H(2)O(2). The cytotoxicity of
      the theaflavin mixture was due, in part, to the generation in the cell culture
      medium of H(2)O(2), which lessened the intracellular levels of glutathione in the
      CAL27 cells and, to a lesser extent, in the GT1 cells. For both cell types,
      coexposures of the theaflavin mixture with catalase or CoCl(2) afforded
      protection.

PMID- 16297595
TI  - The effect of conation in determining the differential variance among brain
      damaged and nonbrain-damaged persons across a broad range of neuropsychological
      tests.
AB  - Conation, or the ability to apply one's abilities purposefully, persistently and
      effectively as required by the task at hand, has been considered historically to
      be an important element of psychology, but has been relatively neglected in
      clinical neuropsychology. Nevertheless, conation may well be a significant
      missing variable in predicting a person's success in practical situations based
      on neuropsychological test scores. This study listed 19 tests from the Halstead
      Reitan battery in order of their predicted dependence on conation. Differences
      between a brain-damaged group and a control group were determined through
      computation of t-ratios. The rank-ordering of the 19 tests according to their
      requirement of conation and the magnitude of the t-ratios were closely
      correlated, yielding a rank-difference coefficient of 0.84. These results suggest
      that conation is a strong factor in determining differential performances on
      neuropsychological tests. Further research is required to identify the role of
      conation in determining the ecological validity of neuropsychological test
      results.

PMID- 16297596
TI  - Sequence variation in NPC1L1 and association with improved LDL-cholesterol
      lowering in response to ezetimibe treatment.
AB  - Niemann-Pick C1-like 1 (NPC1L1) is an intestinal cholesterol transporter and the
      molecular target of ezetimibe, a cholesterol absorption inhibitor demonstrated to
      reduce LDL-cholesterol (LDL-C) both as monotherapy and when co-administered with
      3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins).
      Interestingly, significant interindividual variability has been observed for
      rates of intestinal cholesterol absorption and LDL-C reductions at both baseline
      and post ezetimibe treatment. To test the hypothesis that genetic variation in
      NPC1L1 could influence the LDL-C response to ezetimibe, we performed extensive
      resequencing of the gene in 375 apparently healthy individuals and genotyped
      hypercholesterolemic patients from clinical trial cohorts. No association was
      observed between NPC1L1 single-nucleotide polymorphism and baseline cholesterol.
      However, significant associations to LDL-C response to treatment with ezetimibe
      were observed in patients treated with ezetimibe in two large clinical trials.
      Our data demonstrate that DNA sequence variants in NPC1L1 are associated with an
      improvement in response to ezetimibe pharmacotherapy and suggest that detailed
      analysis of genetic variability in clinical trial cohorts can lead to improved
      understanding of factors contributing to variable drug response.

PMID- 16297597
TI  - Functional interactions between the alpha1b-adrenoceptor and Galpha11 are
      compromised by de-palmitoylation of the G protein but not of the receptor.
AB  - Both the alpha1b-adrenoceptor and Galpha11 are targets for post-translational
      thio-acylation that is regulated by agonist occupancy of the receptor [P.A.
      Stevens, J. Pediani, J.J. Carrillo, G. Milligan, J. Biol. Chem. 276 (2001)
      35883]. In co-expression studies mutation of the sites of thio-acylation in the G
      protein or treatment of cell membranes with hydroxylamine greatly reduced agonist
      stimulation of guanosine 5'-[gamma-[35S]thio]triphosphate ([35S]GTPgammaS)
      binding. In alpha1b-adrenoceptor-Galpha11 fusion proteins mutation of thio
      acylation sites in receptor or G protein did not alter the binding affinity of
      the antagonist [3H]prazosin or the agonist phenylephrine. Although the potency of
      phenylephrine to stimulate binding of [35S]GTPgammaS to alpha1b-adrenoceptor
      Galpha11 fusion proteins was unaffected by the thio-acylation potential of either
      element, the maximal effect was reduced by some 50% when the G protein but not
      the receptor was mutated to prevent thio-acylation. This reflected lack of thio
      acylation of the G protein rather than mutation of Cys9 and Cys10 to Ser because
      treatment with hydroxylamine mimicked this in fusions containing the wild type G
      protein but was without effect in those mutated to prevent thio-acylation.
      Mutation to reduce binding of beta/gamma to Galpha11 markedly reduced
      phenylephrine stimulation of [35S]GTPgammaS binding. Combination of mutations to
      prevent thio-acylation and beta/gamma binding did not, however, have an additive
      effect on [35S]GTPgammaS binding. These results indicate that the thio-acylation
      status of the alpha1b-adrenoceptor does not regulate G protein activation whereas
      thio-acylation of Galpha11 plays a key role in activation by the receptor beyond
      providing membrane association and proximity.

PMID- 16297598
TI  - Neural anomalies during visual search in schizophrenia patients and unaffected
      siblings of schizophrenia patients.
AB  - Schizophrenia patients and their unaffected first-degree relatives exhibit
      performance deficits on attention tasks, perhaps indicating genetic influence
      over attentional abnormalities in schizophrenia. To identify anomalous brain
      function associated with attention in individuals who likely have unexpressed
      genetic liability for schizophrenia, we studied electrophysiological
      characteristics of unaffected siblings of schizophrenia patients during a visual
      serial search task. We gathered behavioral and electrophysiological data from 19
      schizophrenia patients, 18 unaffected biological siblings of schizophrenia
      patients, and 19 nonpsychiatric control participants during performance of the
      Span of Apprehension (Span) task and a control task. Schizophrenia patients had
      lower Span task accuracy than the other two groups. Schizophrenia and sibling
      groups exhibited diminished late positive potentials (P300) over parietal brain
      regions during Span trials. Compared to control task stimuli, attentional demands
      of Span stimuli elicited augmented early negative potentials (N1, P2) over
      posterior brain regions. The degree of augmentation was reduced in schizophrenia
      patients but not in siblings compared to control subjects. Unaffected siblings of
      schizophrenia patients appear to modulate early attentional functions of
      posterior brain regions more effectively than schizophrenia patients but show
      later electrophysiological anomalies suggestive of abnormal updating of task
      relevant information. While the latter may reflect neural mechanisms predisposing
      performance deficits on attentional tasks, the former may reflect compensatory
      processes present in unaffected relatives of schizophrenia patients.

PMID- 16297599
TI  - Defining subjects at risk for psychosis: a comparison of two approaches.
AB  - The ability to detect individuals at high risk for developing schizophrenia
      before they express the disease will lead to targeted early intervention. It has
      been proposed that subjects at risk share a core deficit with people who already
      have schizophrenia. This includes cognitive impairment, affective symptoms,
      social isolation and decline in social functioning. In a sample of 104 help
      seeking patients from a specialised outpatient clinic we investigated how well
      two different sets of criteria define the at-risk group and capture this core
      deficit. One set of criteria is the well-established ultra high-risk model of
      McGlashan et al. [McGlashan 2001 (SIPS) McGlashan, T. H., Miller, T. J., Woods,
      S. W., et al. (2001) Structured Interview for Prodromal Syndromes (Version 3.0,
      unpublished manuscript). New Haven, Connecticut: PRIME Research Clinic, Yale
      School of Medicine.]; the other criteria were those defined by Cornblatt et al.
      [Cornblatt, B., Lencz, T., Smith, C.W., Correll, C.U., Auther, A., Nakayama, E.,
      2003. The schizophrenia prodrome revisited: a neurodevelopmental perspective.
      Schizophr. Bull. 29, 633-651.]. There was considerable overlap in the two sets of
      criteria. However, when the basic symptoms of Klosterkotter [Klosterkotter, J.,
      Hellmich, M., Steinmeyer, E.M., Schultze-Lutter, F., 2001a. Diagnosing
      schizophrenia in the initial prodromal phase. Arch. Gen. Psychiatry, 58, 158
      164.] were included in the McGlashan et al. model, a more narrow and homogeneous
      group was defined.

PMID- 16297600
TI  - Suicidality in schizophrenia as a separate symptom domain that may be independent
      of depression or psychosis.

PMID- 16297602
TI  - The importance and identification of regulatory polymorphisms and their
      mechanisms of action.
AB  - The search for the genetic variations underlying all human phenotypes is in its
      infancy but must be one of the long term goals of the scientific community. There
      is evidence that most, if not all human phenotypes, including illnesses are
      influenced by the genetic makeup of the individual. There are an estimated 11
      million human genetic polymorphisms with a minor allele frequency >1% and
      possibly many times that number of rare sequence variants. The proportion of
      these sequence variants which have any functional effect is unknown but it is
      likely that the majority of those which influence illness lie outside of the
      amino acid coding regions of genes, and affect the regulation of gene expression-
      these are called rSNPs. Recent research suggests that about 50% of genes have one
      or more common rSNPs associated with them and probably most if not all genes have
      an rSNP within the human population. In the long term, determining which
      polymorphisms are potentially functional must be done bio-informatically using
      algorithms based upon experimental data. However, at the current time, the
      limited data that has been obtained does not allow the creation of such an
      algorithm. In vitro studies suggest that a large proportion of rSNPs lie within
      the core and proximal promoter regions of genes but it is not clear how the
      majority of these influence transcription, as they do not appear to be within any
      known transcription factor binding sites. However, promoter regions possess a
      number of sequence-dependent characteristics which make them distinct from the
      rest of the genome, namely stability, curvature and flexibility. Subtle changes
      to these features may underlie the mechanisms by which many polymorphisms exert
      their function.

PMID- 16297601
TI  - Does negative symptom change relate to neurocognitive change in schizophrenia?
      Implications for targeted treatments.
AB  - Negative symptoms and cognitive dysfunction are among the most challenging
      obstacles in the treatment of schizophrenia. It is unknown to what extent they
      are overlapping or independent disease processes. In the search for targeted
      treatments of negative symptoms and cognitive impairments, it is imperative to
      determine their longitudinal relationship. 267 stable outpatients with
      schizophrenia in a work and cognitive rehabilitation program were evaluated using
      symptom measures and a comprehensive neuropsychological test battery at baseline
      and at the conclusion of rehabilitation, 6 months later. Baseline negative
      symptom, neuropsychological variables and change scores from intake to follow-up
      on these variables were correlated. These analyses were repeated with a subsample
      (n = 161) who had clinically significant negative symptoms at baseline. ANCOVA's
      were performed to compare patients whose negative symptoms improved by 5 points
      or more (n = 69) with those whose negative symptoms got worse by 5 points or more
      (n = 26) on their neurocognitive performance at follow-up. Intake negative
      symptoms were significantly associated with theory of mind and visuomotor
      processing. Results failed to support a lawful relationship between change in
      negative symptoms and neurocognition. These findings suggest that negative
      symptoms and neurocognition should be viewed as relatively independent targets
      for intervention.

PMID- 16297603
TI  - Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non
      geriatric outpatients with major depressive disorder (Part II).
AB  - The objective of this study was to investigate the relative impact of brain white
      matter hyperintensities (WMHs), cardiovascular risk factors and elements of the
      one-carbon cycle metabolism (including serum folate, vitamin B12 and homocysteine
      levels) on the outcome of antidepressant treatment in non-elderly subjects with
      major depressive disorder (MDD). Fifty MDD subjects were administered brain
      magnetic resonance imaging (MRI) scans at 1.5 T to detect T2 WMHs. The severity
      of brain WMHs was classified with the Fazekas scale (range=0-3). We assessed
      cardiovascular risk factors in all MDD subjects (age, gender, smoking, diabetes,
      family history, hypertension, cholesterol). MDD patients also had serum folate,
      vitamin B12 and homocysteine levels measured. All MDD subjects received treatment
      with fluoxetine 20 mg/day for 8 weeks. In a logistic regression, the severity of
      subcortical WMHs and the presence of hypofolatemia were independent predictors of
      lack of clinical response to antidepressant treatment. Separately, hypofolatemia
      also predicted lack of remission to antidepressant treatment. These associations
      were independent of the presence of smoking, diabetes, family history,
      hypercholesterolemia, hyperhomocysteinemia and low B12 levels. Although
      preliminary, the results of the present work suggest that subcortical brain WMHs
      and hypofolatemia may have an independent negative impact on the likelihood of
      responding to antidepressant treatment in non-geriatric subjects with MDD.

PMID- 16297605
TI  - Effect of worry on regional cerebral blood flow in nonanxious subjects.
AB  - Several studies suggest that cognitive tasks attenuate activation of the limbic
      system by emotional stimuli. We investigated the possibility that worry would
      similarly inhibit the limbic system by examining its effects on regional cerebral
      blood flow (rCBF). Ten nonanxious volunteers underwent four scans within one
      session, using positron emission tomography (PET) with H(2)(15)O as tracer. The
      first two scans recorded emotionally neutral thinking induced after listening to
      tapes describing neutral statements. Preceding the third and fourth scans,
      subjects listened to the self-recorded tape describing their individual worries,
      were instructed to continue to worry, and were scanned 5 min later. Subjects
      rated themselves as more anxious during the worry scans but showed no significant
      heart interbeat or skin conductance changes. During worry, rCBF increases were
      found bilaterally in the medial fronto-orbital gyri and the right thalamus; rCBF
      decreases were found bilaterally in the hippocampi and amygdalae, in the right
      insula, the left and right inferior, middle and superior temporal gyri and the
      occipito-temporal gyri, the right inferior occipital gyrus and the left
      supramarginal gyrus. Activity of the left orbito-frontal gyrus was negatively
      correlated with activity of the amygdalae. The results support the hypothesis
      that worry-induced prefrontal activity suppresses affect-related subcortical
      regions.

PMID- 16297604
TI  - Volume and neuron number of the mediodorsal thalamic nucleus in schizophrenia: a
      replication study.
AB  - Previous neuropathological studies on the mediodorsal thalamic nucleus (MD) in
      schizophrenia have yielded conflicting results. While some studies suggested that
      patients with schizophrenia have a pronounced reduction of the volume and neuron
      number in the MD, more recent data have not found anatomical alterations in this
      thalamic nucleus. However, most studies have considerable methodological
      shortcomings. In the present study, we investigated the volume, neuron density
      and neuron number in the left and right MD in patients with schizophrenia (n=20)
      and normal control subjects without neuropsychiatric disorders (n=18). Patients
      with schizophrenia showed no significant difference in neuron density and total
      neuron number in the MD. Compared with the control group, patients with
      schizophrenia had a smaller MD volume in both hemispheres, a difference that
      approached significance in the left MD (-7.3%) when the whole brain volume was
      included as a covariate. No significant main group effect of diagnosis was found
      for the right MD volume. There were no significant correlations between MD
      volume, neuron density, total neuron number and the duration of illness or the
      age of the patients. Taken together, the present results suggest that
      schizophrenia is associated with a moderate volume reduction in the left
      mediodorsal thalamic nucleus, while the neuron density and the total neuron
      number are unchanged.

PMID- 16297606
TI  - Brain processes associated with target finding.
AB  - The response execution stage of cognitive skill consists of several substages,
      including finding the proper response location among available alternatives and
      moving the effector to the target location. In order to unravel the brain
      dynamics associated with the finding process, the present experiments used two
      experimental conditions. In the number condition, which requires both finding and
      moving, subjects are presented on each trial with a digit, 0-9, are required to
      find that digit on a circular clock face, and then to move a cursor to that
      target's location. In the arrow condition, an arrow pointing to the location of
      the target on the clock face circumference appears simultaneously with the target
      digit; no target finding is required because subjects need only to move the
      cursor along the path marked by the arrow. A pilot and the main experiment
      revealed that response initiation times but not movement times were affected by
      these experimental manipulations. Analysis of magnetoencephalographic (MEG)
      activity revealed an early occipital activity which was not affected by
      experimental manipulations. Later activity with central-parietal and parieto
      temporal loci presumably reflected changes in the dorsal and ventral pathways,
      respectively, and these were affected by experimental conditions. Finally,
      finding processes seem to be associated with a second late activation of the
      ventral pathway presumably reflecting ongoing recognition processes.

PMID- 16297607
TI  - Dose responses of three 4-aminopyridine derivatives on axonal conduction in
      spinal cord trauma.
AB  - To explore novel treatments for enhancing conduction through traumatically
      injured spinal cord we have synthesized structurally distinct pyridine based
      compounds; N-(4-pyridyl) methyl carbamate, N-(4-pyridyl) ethyl carbamate, and N
      (4-pyridyl) t-butyl carbamate. With the use of a double sucrose gap-recording
      chamber we perform a dose-response assay to examine the effects of these
      compounds on axonal conduction following an in vitro stretch injury. The tested
      compounds significantly enhanced axonal conduction to the stretch injured cord at
      1 microM, a dose that coincides with the clinically relevant dose of potassium
      channel blocker 4-aminopyridine (4-AP). Methyl carbamate enhanced conduction
      maximally at 100 microM. This is also the most effective concentration of 4-AP in
      vitro. The other compounds ethyl carbamate and t-butyl carbamate enhanced
      conduction maximally at lower concentrations of 10 and 1 microM. At higher
      concentrations each of these compounds continued to increased CAP amplitude,
      however not significantly. Additionally, two of the compounds ethyl and t-butyl
      carbamate appear to have negative effects on CAP amplitude when administered at
      or beyond 100 microM. These compounds demonstrate the possibility that
      derivatives of 4-AP can retain the ability to increase axonal conduction in the
      injured spinal cord.

PMID- 16297609
TI  - Clinical benchmarking for the validation of AI medical diagnostic classifiers.

PMID- 16297608
TI  - [Which sedation scale should be used in the paediatric intensive care unit? A
      comparative prospective study].
AB  - OBJECTIVES: To compare pain and sedation assessments by nurses undertaken with
      the Objective Pain Scale (OPS) and a Visual Analogue Scale (VAS) to the current
      reference scale for paediatric intensive care that is the COMFORT scale. To
      compare the unmodified COMFORT scale to a COMFORT "behaviour" scale which does
      not include physiologic items. To evaluate the ease of use of these scales.
      METHODS: This prospective observational comparative study was carried out in
      children aged 1 year or older who were admitted in an intensive care unit. At 2
      to 3 time points within 24 hours, a pain sedation assessment was carried out by
      the nurse in charge of the child with COMFORT scale, OPS and VAS. Correlation
      tests were used to compare the scores of each scale. RESULTS: Nurses recorded 55
      assessments in 20 children. Correlation studies showed a poor correlation between
      OPS, VAS and the COMFORT scale (Spearman's r=0.54 and 0.53 respectively) and a
      strong correlation between the COMFORT scale and the COMFORT "behaviour" scale
      (Spearman's r=0.96). The COMFORT behaviour scale was the most frequently fully
      completed scale. CONCLUSION: Among the 3 scales compared to the COMFORT scale in
      this study, the COMFORT "behaviour" scale was the only one to show a strong
      correlation and it also seemed to be the easiest to use.

PMID- 16297611
TI  - The potential of recycling and reusing municipal solid waste incinerator ash in
      Taiwan.
AB  - By 2004, there were 19 municipal solid waste incinerators (MSWI) with a total
      yearly treatment capacity of 7.72 million tons in service in Taiwan. All 19
      incinerators operated daily to generate about 1.05 million tons of incinerator
      ash, including bottom ash and stabilized fly ash in 2003, and the average ash
      yield is 18.67%. The total number of incinerators is expected to increase to 27,
      serving almost all cities in Taiwan by 2007. The authors have suggested a set of
      criteria based on the yield of incinerator ash (Phi) to study the ash recycle and
      reuse potential. The Taiwan Environmental Protection Administration has studied
      the treatment and reuse of MSWI ashes for many years and collected references on
      international experience accumulated by developed nations for establishing
      policies on treatment and reuse of MSWI ashes. These citations were analyzed as
      the basis for current governmental decision making on policies and factors to be
      considered for establishing policies on recycle and reuse of MSWI ashes. Feasible
      applications include utilization of ashes, which after sieving and separation of
      metal particles, produce granular materials. When granular materials comply with
      TCLP limitations, they can be utilized as cement additives or road base. The
      procedures of evaluation have been proposed in the performance criteria to be
      included in the proposed decision-making process of ash utilization.

PMID- 16297610
TI  - Effect of prostaglandins against alloxan-induced diabetes mellitus.
AB  - Previously, we observed that alloxan-induced in vitro cytotoxicity and apoptosis
      in an insulin secreting rat insulinoma, RIN, cells was prevented by prior
      exposure to prostaglandin (PG) E(1), PGE(2), PGI(2), PGF(1)(alpha), and
      PGF(3)(alpha) (P<0.05 compared to alloxan), whereas thromboxane B(2) (TXB(2)) and
      6-keto-PGF(1)(alpha) were ineffective. In an extension of these studies, we now
      report that prior intraperitoneal administration of PGE(1), PGE(2),
      PGF(1)(alpha), and PGF(3)(alpha) prevented alloxan-induced diabetes mellitus in
      male Wistar rats, whereas PGI(2), TXB(2), and 6-keto PGF(1)(alpha) were not that
      effective. PGE(1), PGE(2), PGF(1)(alpha), and PGF(3)(alpha) not only attenuated
      chemical-induced diabetes mellitus but also restored the antioxidant status to
      normal range in red blood cells and pancreas. These results suggest that PGE(1),
      PGE(2), PGF(1)(alpha), and PGF(3)(alpha) can abrogate chemically induced diabetes
      mellitus in experimental animals and attenuate the oxidant stress that occurs in
      diabetes mellitus.

PMID- 16297612
TI  - Piezoelectric biosensor using olfactory receptor protein expressed in Escherichia
      coli.
AB  - An olfactory receptor protein of C. elegans, ODR-10, was expressed in Escherichia
      coli as a fusion protein, with GST and 6x His-tag. The expression of the target
      protein was analyzed by SDS-PAGE and Western blot, and was confirmed to be
      expressed at the membrane fraction of the host E. coli. The surface of a quartz
      crystal microbalance (QCM) was coated with crude membrane extracts, containing
      the expressed receptor protein, and the interaction between the olfactory
      receptor and various odorant molecules examined. Compared with other odorants,
      diacetyl (2,3-butanedione), known as a natural ligand for the ODR-10 receptor,
      interacted most strongly with the expressed protein. Various concentrations of
      diacetyl were applied to the expressed ODR-10 receptor, and the response of the
      QCM showed a linear relationship to the logarithmic value of the odorant
      concentration. This piezoelectric biosensor system, using olfactory receptor
      proteins expressed in E. coli, can be used in diagnostics, toxic chemical
      detection and the quality control of food.

PMID- 16297613
TI  - DNA-Cu(II) poly(amine) complex membrane as novel catalytic layer for highly
      sensitive amperometric determination of hydrogen peroxide.
AB  - A novel hydrogen peroxide biosensor was fabricated by using a DNA-Cu(II) complex
      as a novel electrocatalyst for the reduction of hydrogen peroxide (H2O2). A
      polyion complex (PIC) membrane composed of DNA and poly(allylamine) (PAA)
      functioned as a support matrix for immobilization of electrocatalytic element
      copper ion. The circular dichroism (CD) spectrum of the DNA-Cu(II)/PAA membrane
      in wet state showed that the DNA exists in B-like form within the membrane.
      Electrochemical measurements of the DNA-Cu(II)/PAA membrane-modified glassy
      carbon (GC) electrode revealed that the copper ion embedded in the DNA/PAA layer
      exhibits good electrochemical behaviors, and the electrochemical rate constant
      between the immobilized copper ion and the GC electrode surface was estimated to
      be 26.4 s(-1). The resulting DNA-Cu(II)/PAA/GC electrode showed an excellent
      electrocatalytic activity for the H2O2 reduction. The sensitivity of the sensor
      for the determination of H2O2 was affected by the amount of each component, such
      as copper ion, DNA and PAA in the DNA-Cu(II)/PAA membrane. Effects of applied
      potential, pH, temperature, ionic strength and buffer concentrations upon the
      response currents of the sensor were also investigated for an optimum analytical
      performance. Even in the presence of dissolved oxygen, the sensor exhibited
      highly sensitive and rapid (response time, less than 5 s) response to H2O2. The
      steady-state cathodic current responses of the sensor obtained at -0.2 V versus
      Ag/AgCl in air-saturated 50 mM phosphate buffer (pH 5.0) increased linearly up to
      135 microM with the detection limit of 50 nM. Interference by ascorbic acid and
      uric acid due to the reduction of Cu(II) was effectively cancelled by further
      modification of outermost layer of polyion complex film. In addition, the sensor
      exhibited good reproducibility and stability.

PMID- 16297614
TI  - Combined radiotherapy, 5-fluorouracil continuous infusion and weekly oxaliplatin
      in advanced rectal cancer: a phase I study.
AB  - The aim of this study was to determine the maximum-tolerated dose (MTD) of weekly
      oxaliplatin combined with 5-fluorouracil (5FU) continuous infusion administered
      concomitantly with fractionated radiotherapy in patients presenting advanced
      rectal cancer. Forty-three patients with rectal cancer (stage T3/T4 (n = 24),
      metastatic (n = 17) and 2 with local recurrence), were included. The radiotherapy
      dose delivered was 45 Gy over 5 weeks (1.8 Gy/fraction/day, 5 days per week). The
      initial weekly oxaliplatin dosage was 30 mg/m2 and the 5FU dosage 150 mg/m2/d.
      The oxaliplatin and 5FU doses were escalated. Eight dose levels were tested. At
      dose level 8 (oxaliplatin 80 mg/m2, 5FU 225 mg/m2/d), 2 patients out of 4
      presented dose-limiting toxicity (severe diarrhoea with dehydration and fatal
      shock, rectovesical fistula). At dose level 7, 2 further patients presented with
      grade 3 diarrhoea. The main toxicity of the combination was diarrhoea. The
      hematological and neurological toxicities were not severe and were not dose
      limiting. Out of the 30 patients undergoing surgery, 4 (13.3%) presented with
      pathological complete response and 4 (13.3%) only presented with microscopic
      residual disease. The results from this study enabled determination of the
      recommended weekly oxaliplatin dose (60 mg/m2) combined with 5FU continuous
      infusion (225 mg/m2) and fractionated radiotherapy (45 Gy) in the pre-operative
      treatment of advanced rectal cancer. The good safety profile of the regimen,
      associated with promising results in terms of histological response, suggest that
      the regimen could be developed in future phase II/III studies.

PMID- 16297615
TI  - Isolation, structure elucidation, antioxidative and immunomodulatory properties
      of two novel dihydrocoumarins from Aloe vera.
AB  - Two new dihydrocoumarin derivatives, compounds 1 and 2, were isolated from Aloe
      vera. Their structures were determined by X-ray crystallographic diffraction
      analysis and extensive 1D, 2D NMR spectroscopic data. Both of them evidently
      showed antioxidant activity against superoxide and hydroxyl radicals. Only 1
      obviously exhibited immunomodulatory activity in relation to increasing the
      phagocytic activity and stimulating the production of superoxide anions in the
      oxygen respiratory burst of rat peritoneal macrophages.

PMID- 16297616
TI  - Inactivation of medium-chain acyl-CoA dehydrogenase by oct-4-en-2-ynoyl-CoA.
AB  - Mitochondrial medium-chain acyl-CoA dehydrogenase is a key enzyme for the beta
      oxidation of fatty acids, which catalyzes the FAD-dependent oxidation of a
      variety of acyl-CoA substrates to the corresponding trans-2-enoyl-CoA thioesters.
      Oct-4-en-2-ynoyl-CoA was identified as a new irreversible inhibitor of acyl-CoA
      dehydrogenase, and kinetic parameters K(I) and k(inact) were determined to be 11
      microM and 0.025 min(-1), respectively. Triple bond between C2 and C3 of the
      inhibitor was identified as the functional group responsible for enzyme
      inactivation, and Michael addition is proposed as the mechanism for this
      inactivation, which is a new pathway for inactivation of MCAD by inhibitors. The
      inhibitor may become a lead for further development for treating non-insulin
      dependent diabetes mellitus.

PMID- 16297617
TI  - Reduction of CYP450 inhibition in the 4-[(1H-imidazol-4-yl)methyl]piperidine
      series of histamine H3 receptor antagonists.
AB  - A novel series of histamine H3 receptor antagonists based on the 4-[(1H-imidazol
      4-yl)methyl]piperidine template displaying low CYP2D6 and CYP3A4 inhibitory
      profiles has been identified. Structural features responsible for the reduction
      of P450 activity, a typical liability of 4-substituted imidazoles, have been
      established.

PMID- 16297618
TI  - Synthesis and structure-activity relationships of novel dipeptides and reduced
      dipeptides as ligands for melanocortin subtype-4 receptor.
AB  - A series of benzylic piperazines (e.g., 4 and 5) attached to an 'address
      element', the dipeptide H-D-Tic-D-p-Cl-Phe-OH, 3 has been identified as ligands
      for the melanocortin subtype-4 receptor (MC4R). We describe herein the structure
      activity relationship (SAR) studies on the N-terminal residue of the 'address
      element'. Several novel dipeptides and reduced dipeptides with high MC4R binding
      affinities and selectivity emerged from this SAR study.

PMID- 16297619
TI  - Synthesis and evaluation of 2-anilino-3-phenylsulfonyl-6-methylpyridines as
      corticotropin-releasing factor1 receptor ligands.
AB  - A novel series of 2-anilino-3-phenylsulfonyl-6-methylpyridines was synthesized
      and evaluated as corticotropin-releasing factor receptor ligands. Structure
      activity relationship studies focused primarily on optimization of the 3
      phenylsulfonyl group. Compounds within this series were identified which showed
      potent binding affinity for the CRF1 receptor. Selected compounds were examined
      in a rat pharmacokinetic study and were found to have oral bioavailabilities
      ranging from 16 to 35%.

PMID- 16297620
TI  - Novel endoperoxides: synthesis and activity against Candida species.
AB  - Fifteen new endoperoxides have been synthesised and tested for activity against
      pathogenic Candida species. These endoperoxides can be prepared in high yields,
      in one to three steps, from inexpensive starting materials. Despite chemical and
      structural similarities, their inhibitory activity against Candida growth varied
      greatly from one endoperoxide to another, and one species to another. This study
      of susceptibility to endoperoxide compounds presented here may lead to the
      development of potent new antifungal agents.

PMID- 16297621
TI  - Pyridobenzodiazepines: a novel class of orally active, vasopressin V2 receptor
      selective agonists.
AB  - Our efforts in seeking low molecular weight agonists of the antidiuretic peptide
      hormone arginine vasopressin (AVP) have led to the identification of the clinical
      candidate WAY-151932 (VNA-932). Further exploration of the structural
      requirements for agonist activity has provided another class of potent, orally
      active, non-peptidic vasopressin V2 receptor selective agonists exemplified by
      the 5,11-dihydro-pyrido[2,3-b][1,5]benzodiazepine as a candidate for further
      development.

PMID- 16297622
TI  - Synthesis of 1-(3',4',5'-trimethoxy) phenyl naphtho[2,1b]furan as a novel
      anticancer agent.
AB  - 3',4',5'-Trimethoxy benzoyl-naphthalene 2-O-acetic acid (5) underwent base
      catalysed intramolecular condensation to yield exclusively 1-(3',4',5'
      trimethoxy) phenyl naphtho[2,1-b]furan 8. The cyclised product 8 has been
      characterised by spectroscopy. The product 8 showed significant anticancer
      activity against human cancer cell lines COLO320DM (colon), CaCO2 (colon) and
      WRL68 (liver) at 0.7, 0.65 and 0.50 microg/ml concentrations, respectively, in
      the in vitro MTT assay.

PMID- 16297623
TI  - Synthesis of complex-type glycans derived from parasitic helminths.
AB  - Chemical synthesis of complex-type glycans 1 and 2 derived from eggs of parasitic
      helminths, Schistosoma mansoni and Schistosoma japonicum, is described. These
      branched sugar chains were synthesized regio- and stereoselectively by using beta
      mannosylation, desilylation under high pressure, and glycosylation in frozen
      solvent as key transformations.

PMID- 16297624
TI  - Novel fluorescent labelled affinity probes for diadenosine-5',5'''-P1,P4
      tetraphosphate (Ap4A)-binding studies.
AB  - Tandem synthetic-biosynthetic procedures were used to prepare two novel
      fluorescent labelled affinity probes for diadenosine-5',5'''-P1,P4-tetraphosphate
      (Ap4A)-binding studies. These compounds (dial-mant-Ap4A and azido-mant-Ap4A) are
      shown to clearly distinguish known Ap4A-binding proteins from Escherichia coli
      (LysU and GroEL) and a variety of other control proteins. Successful labelling of
      chaperonin GroEL appears to be allosteric with respect to the well-characterized
      adenosine 5'-triphosphate (ATP)-binding site, suggesting that GroEL possesses a
      distinct Ap4A-binding site.

PMID- 16297625
TI  - Quantitative structure-activity analysis of 5-arylidene-2,4-thiazolidinediones as
      aldose reductase inhibitors.
AB  - Design of aldose reductase (ALR2) inhibitors has received considerable attention.
      Aldose reductase inhibitors, when administered from the onset of hyperglycemia,
      prevent the progression of polyol accumulation-linked complications. The
      feasibility that inhibition of aldose reductase provides a pharmacologically
      direct treatment for diabetic complications that is independent of the control of
      blood sugar levels has spurred the development of structurally diverse aldose
      reductase inhibitors. In this work, we report quantitative structure-activity
      relationship (QSAR) analysis performed by 3D-QSAR analysis, Hansch analysis, and
      Fujita-Ban analysis on a series of 5-arylidene-2,4-thiazolidinediones as aldose
      reductase inhibitors. The 2D & 3D-QSAR models were generated using 18 compounds
      and Fujita-Ban analysis models were obtained using 23 compounds. The predictive
      ability of the resulting 2D and 3D models was evaluated against a test set of 5
      compounds. Analyses of results from the present QSAR study inferred that 3rd
      position of the phenyl ring and acetic acid substitution at N-position of
      thiazolidinediones play a key role in the aldose reductase inhibitory activity.

PMID- 16297626
TI  - Hit-to-Lead studies: the discovery of potent, orally bioavailable
      thiazolopyrimidine CXCR2 receptor antagonists.
AB  - A Hit-to-Lead optimisation programme was carried out on a high throughput
      screening hit, the thiazolopyrimidine 1, resulting in the discovery of the
      potent, orally bioavailable CXCR2 antagonist 29.

PMID- 16297627
TI  - The PHD finger, a nuclear protein-interaction domain.
AB  - The PHD finger is a common structural motif found in all eukaryotic genomes. It
      is a Zn(2+)-binding domain and its closest structural relative is the RING
      domain. Many RING fingers bind to E2 ligases to mediate the ubiquitination of
      proteins. Whether PHD fingers share a common function is unclear. Notably, many
      if not all PHD fingers are found in nuclear proteins whose substrate tends to be
      chromatin. Some PHD fingers bind to specific nuclear protein partners, apparently
      through the same surface that is used by RING domains to bind their cognate E2
      ligases. New evidence also suggests that some PHD fingers bind to nucleosomes,
      raising the possibility that chromatin might be a common nuclear ligand of PHD
      fingers.

PMID- 16297628
TI  - Inhibition of tumor angiogenesis by a natural fragment of a tRNA synthetase.
AB  - Human tyrosyl- and tryptophanyl-tRNA synthetases (TyrRS and TrpRS, respectively)
      link protein synthesis to signal-transduction pathways, including angiogenesis.
      Fragments of TyrRS stimulate angiogenesis, whereas those of TrpRS (T2-TrpRS)
      inhibit angiogenesis. Thus, these two synthetases acquired opposing activities
      during evolution, possibly as a coordinated mechanism for regulating
      angiogenesis. The recent identification of the cellular target of T2-TrpRS sheds
      light into the mechanism of angiogenesis inhibition. This mechanism provides a
      molecular basis for the lack of effect of T2-TrpRS on the normal vasculature.
      With these features, we suggest that this fragment of a tRNA synthetase might
      safely be used to arrest neovascularization of tumors. In particular, an anti
      angiogenesis agent that stops the growth of tumor vessels without affecting
      normal vessels might serve as an adjunct to cytotoxic therapy.

PMID- 16297629
TI  - 2-Benzyl and 2-phenyl-3-hydroxypropyl pivalates as protein kinase C ligands.
AB  - A series of 2-benzyl and 2-phenyl-3-hydroxypropyl pivalates designed to
      incorporate the principal pharmacophores of phorbol esters have been synthesized
      and tested as PKC-alpha ligands. Among the analogues, 13c exhibited the most
      potent binding affinity with a Ki = 0.7 microM. The synthesized analogues were
      subjected to molecular modeling analysis based on two alternative models of the
      phorbol pharmacophore and a docking study of 13c was carried out.

PMID- 16297630
TI  - An evaluation of automated in silico ligand docking of amino acid ligands to
      Family C G-protein coupled receptors.
AB  - Family C G-protein coupled receptors (GPCRs) consist of the metabotropic
      glutamate receptors (mGluRs), the calcium-sensing receptor (CaSR), the T1R taste
      receptors, the GABA(B) receptor, the V2R pheromone receptors, and several
      chemosensory receptors. A common feature of Family C receptors is the presence of
      an amino acid binding pocket. The objective of this study was to evaluate the
      ability of the automatic docking program FlexX to predict the favored amino acid
      ligand at several Family C GPCRs. The docking process was optimized using the
      crystal structure of mGluR1 and the 20 amino acids were docked into homology
      models of the CaSR, the 5.24 chemosensory receptor, and the GPRC6A amino acid
      receptor. Under optimized docking conditions, glutamate was docked in the binding
      pocket of mGluR1 with a root mean square deviation of 1.56 angstroms from the co
      crystallized glutamate structure and was ranked as the best ligand with a
      significantly better FlexX score compared to all other amino acids. Ligand
      docking to a homology model of the 5.24 receptor gave generally correct
      predictions of the favored amino acids, while the results obtained with models of
      GPRC6A and the CaSR showed that some of the favored amino acids at these
      receptors were correctly predicted, while a few other top scoring amino acids
      appeared to be false positives. We conclude that with certain caveats, FlexX can
      be successfully used to predict preferred ligands at Family C GPCRs.

PMID- 16297631
TI  - Quaternary ammonium substituted thieno[3,2-e]-1,2-thiazine-6-sulfonamide 1,1
      dioxides: Potential membrane-impermeable inhibitors of carbonic anhydrase.
AB  - Thieno[3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxides, which have a quaternary
      ammonium moiety incorporated into their structures, were synthesized. All of the
      quaternary ammonium salts prepared in the present study are potent inhibitors of
      both human carbonic anhydrase-II and recombinant human carbonic anhydrase-IV;
      they are significantly more potent as inhibitors of these carbonic anhydrase
      isozymes than the previously reported inhibitor quaternary ammonium
      homosulfanilamide. By virtue of the permanent cationic charge on these compounds
      they are anticipated to be membrane-impermeable inhibitors of carbonic anhydrase.
      Spiro quaternary ammonium compounds, such as 15 and 16, when formed by
      intracellular cyclization following transport of a suitable precursor molecule,
      such as 14, may be selective prolonged inhibitors of cytosolic carbonic anhydrase
      due to intracellular entrapment.

PMID- 16297632
TI  - Development of 3,4-dihydro-2H-benzo[1,4]oxazine derivatives as dual thromboxane
      A2 receptor antagonists and prostacyclin receptor agonists.
AB  - We discovered a novel series of 3,4-dihydro-2H-benzo[1,4]oxazin-8-yloxyacetic
      acid derivatives as potent dual-acting agents to block the TXA2 receptor and to
      activate the PGI2 receptor. We report the synthesis, structure-activity
      relationship, and in vitro, ex vivo, and in vivo pharmacology of this series of
      compounds. 4-[2-(1,1-Diphenylethylsulfanyl)ethyl]-3,4-dihydro-2H-benzo[1,4]oxazin
      8-yloxyacetic acid N-methyl-D-glucamine salt (7) is a promising candidate for a
      novel treatment in the anti-thrombotic and the cardiovascular fields avoiding
      hypotensive side effects.

PMID- 16297633
TI  - Multiple-component radiation-measurement error models.
AB  - Measurement error modeling and assessment are crucial to any assay method.
      Realistic error models prioritize future efforts to reduce key error components
      and provide a way to estimate total ("random" and "systematic") measurement
      error. This paper describes multiple-component error models for radiation-based
      assay, gives example applications, and describes strategies for choosing and then
      fitting error models.

PMID- 16297634
TI  - Polyamines modify the components of phospholipids-based signal transduction
      pathway in Coffea arabica L. cells.
AB  - Recent results, fundamentally obtained from animal tissues, suggest that
      polyamines (Pas), essential compounds for the growth and development of all life
      organisms, may interact with a signal transduction cascade. Because Pas are
      highly positive charged compounds, their binding with phospholipids involved in
      signal transduction is likely to be the case. In this work, the in vivo effect of
      Pas on some important components of phospholipid signal transduction pathway was
      studied, by the first time, in plant tissue. Endogenous Pas content varied during
      the culture cycle of Coffea arabica cells: putrescine (Put) levels increased at
      the end of the stationary phase, both spermidine (Spd) and spermine (Spm)
      accumulated at the beginning of the linear growth phase. Cells that were
      incubated with Put presented a significant increase in phospholipase D (PLD) (EC:
      3.1.4.4) activity, phospholipase C (PLC) (EC: 3.1.4.3) activity decreased, and
      the effect on lipid kinases was less marked. However, the incubation of the cells
      with Spd and Spm significantly stimulated the lipid kinases activities,
      fundamentally increased the formation of phosphatidyl inositol 4-phosphate (PIP)
      and phosphatidylinositol 4,5-bisphosphate (PIP2), while the effect on PLC and PLD
      activities was minor when compared with the cells treated with Put. The results
      presented here suggest that Pas may modulate the cellular signal of C. arabica
      cells by differentially affecting components of the phospholipid cascade.

PMID- 16297635
TI  - Isolation and characterization of an alpha-amylase gene in cassava (Manihot
      esculenta).
AB  - The roots of cassava plants (Manihot esculenta Crantz) accumulate starch as their
      major form of carbohydrate reserve. Starch accumulation and properties are
      determined by a balance between starch biosynthesis and degradation processes.
      Alpha-amylases (EC 3.2.1.1) are alpha-1,4 endoglycolytic enzymes, responsible for
      the mobilization of stored carbohydrate reserves by initiating the degradation
      process. Alpha-amylase genes have been shown to be differentially expressed at
      various developmental stages and environmental conditions through the action of
      plant hormones such as abscisic acid (ABA) and gibberellic acid (GA). In this
      study, we isolated an alpha-amylase gene from cassava tuberous roots (designated
      as MEamy2, GenBank accession number DQ011041). The deduced product of MEamy2 is
      407 amino acid residues in length, with a calculated molecular mass of 46.7 kDa
      and an isoelectric point of 8.66. Southern blot analysis showed that the MEamy2
      is present as a single copy in cassava genome. It shares the highest homology
      with AMY8 from apple fruit. The predicted structural model of MEamy2 contains
      three domains, active sites and starch-binding domain that are common with other
      plant alpha-amylases. RT-PCR analysis showed that the MEamy2 gene expression was
      induced in cassava roots within 2 hours after treatment with GA, but not ABA.

PMID- 16297637
TI  - Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and
      oligodendrogenesis from adult stem/progenitor cells.
AB  - Cell renewal in the adult central nervous system (CNS) is limited, and is blocked
      in inflammatory brain conditions. We show that both neurogenesis and
      oligodendrogenesis of adult neural progenitor cells in mice are blocked by
      inflammation-associated (endotoxin-activated) microglia, but induced by microglia
      activated by cytokines (IL-4 or low level of IFN-gamma) associated with T-helper
      cells. Blockage was correlated with up-regulation of microglial production of
      tumor necrosis factor-alpha. The effect induced by IL-4-activated microglia was
      mediated, at least in part, by insulin-like growth factor-I. The IL-4-activated
      microglia showed a bias towards oligodendrogenesis whereas the IFN-gamma
      activated microglia showed a bias towards neurogenesis. It thus appears that
      microglial phenotype critically affects their ability to support or impair cell
      renewal from adult stem cell.

PMID- 16297636
TI  - TNFalpha-induced MMP-9 promotes macrophage recruitment into injured peripheral
      nerve.
AB  - Matrix metalloproteinase-9 (MMP-9) is an extracellular protease that is induced
      hours after injury to peripheral nerve. This study shows that MMP-9 gene deletion
      and neutralization with MMP-9 antibody reduce macrophage content in injured wild
      type nerves. In mice with delayed Wallerian degeneration (WldS), MMP-9 and tumor
      necrosis factor alpha (TNFalpha) decline in association with the reduced
      macrophage recruitment to injured nerve that characterizes this strain of mice.
      We further determined that TNFalpha acts as an MMP-9 inducer by establishing
      increased MMP-9 levels after TNFalpha injection in rat sciatic nerve in vivo and
      primary Schwann cells in vitro. We found reduced MMP-9 expression in crushed
      TNFalpha knockout nerves that was rescued with exogenous TNFalpha. Finally, local
      application of MMP-9 on TNFalpha-/- nerves increased macrophage recruitment to
      the lesion. These data suggest that TNFalpha lies upstream of MMP-9 in the
      pathway of macrophage recruitment to injured peripheral nerve.

PMID- 16297638
TI  - Expression, purification, and characterization of Clostridium botulinum type B
      light chain.
AB  - A full-length synthetic gene encoding the light chain of botulinum neurotoxin
      serotype B, approximately 50 kDa (BoNT/B LC), has been cloned into a bacterial
      expression vector pET24a+. BoNT/B LC was expressed in Escherichia coli
      BL21.DE3.pLysS and isolated from the soluble fraction. The resultant protein was
      purified to homogeneity by cation chromatography and was determined to be >98%
      pure as assessed by SDS-polyacrylamide gel stained with SilverXpress and analyzed
      by densitometry. Mass spectroscopic analysis indicated the protein to be 50.8
      kDa, which equaled the theoretically expected mass. N-terminal sequencing of the
      purified protein showed the sequence corresponded to the known reported sequence.
      The recombinant BoNT/B light chain was found to be highly stable, catalytically
      active, and has been used to prepare antisera that neutralizes against BoNT/B
      challenge. Characterization of the protein including pH, temperature, and the
      stability of the protein in the presence or absence of zinc is described within.
      The influence of pH differences, buffer, and added zinc on secondary and tertiary
      structure of BoNT/B light chain was analyzed by circular dichroism and tryptophan
      fluorescence measurements. Optimal conditions for obtaining maximum
      metalloprotease activity and stabilizing the protein for long term storage were
      determined. We further analyzed the thermal denaturation of BoNT/B LC as a
      function of temperature to probe the pH and added zinc effects on light chain
      stability. The synthetic BoNT/B LC has been found to be highly active on its
      substrate (vesicle associated membrane protein-2) and, therefore, can serve as a
      useful reagent for BoNT/B research.

PMID- 16297639
TI  - Conformation-specific antibodies reveal distinct actin structures in the nucleus
      and the cytoplasm.
AB  - For many years the existence of actin in the nucleus has been doubted because of
      the lack of phalloidin staining as well as the failure to document nuclear actin
      filaments by electron microscopy. More recent findings reveal actin to be a
      component of chromatin remodeling complexes and of the machinery involved in RNA
      synthesis and transport. With distinct functions for nuclear actin emerging, the
      quest for its conformation and oligomeric/polymeric structure in the nucleus has
      resumed importance. We used chemically cross-linked 'lower dimer' (LD) to
      generate mouse monoclonal antibodies specific for different actin conformations.
      One of the resulting antibodies, termed 1C7, recognizes an epitope that is buried
      in the F-actin filament, but is surface-exposed in G-actin as well as in the LD.
      In immunofluorescence studies with different cell lines, 1C7 selectively reacts
      with non-filamentous actin in the cytoplasm. In addition, it detects a discrete
      form of actin in the nucleus, which is different from the nuclear actin revealed
      by the previously described 2G2 [Gonsior, S.M., Platz, S., Buchmeier, S., Scheer,
      U., Jockusch, B.M., Hinssen, H., 1999. J. Cell Sci. 112, 797]. Upon latrunculin
      induced disassembly of the filamentous cytoskeleton in Rat2 fibroblasts, we
      observed a perinuclear accumulation of the 1C7-reactive actin conformation. In
      addition, latrunculin treatment led to the assembly of phalloidin-staining actin
      structures in chromatin-free regions of the nucleus in these cells. Our results
      indicate that distinct actin conformations and/or structures are present in the
      nucleus and the cytoplasm of different cell types and that their distribution
      varies in response to external signals.

PMID- 16297640
TI  - Structure of the cytochrome complex SoxXA of Paracoccus pantotrophus, a heme
      enzyme initiating chemotrophic sulfur oxidation.
AB  - The sulfur-oxidizing enzyme system (Sox) of the chemotroph Paracoccus
      pantotrophus is composed of several proteins, which together oxidize hydrogen
      sulfide, sulfur, thiosulfate or sulfite and transfers the gained electrons to the
      respiratory chain. The hetero-dimeric cytochrome c complex SoxXA functions as
      heme enzyme and links covalently the sulfur substrate to the thiol of the
      cysteine-138 residue of the SoxY protein of the SoxYZ complex. Here, we report
      the crystal structure of the c-type cytochrome complex SoxXA. The structure could
      be solved by molecular replacement and refined to a resolution of 1.9A
      identifying the axial heme-iron coordination involving an unusual Cys-251
      thiolate of heme2. Distance measurements between the three heme groups provide
      deeper insight into the electron transport inside SoxXA and merge in a better
      understanding of the initial step of the aerobic sulfur oxidation process in
      chemotrophic bacteria.

PMID- 16297641
TI  - A new approach to correct the QT interval for changes in heart rate using a
      nonparametric regression model in beagle dogs.
AB  - INTRODUCTION: Over- and/or under-correction of QT intervals for changes in heart
      rate may lead to misleading conclusions and/or masking the potential of a drug to
      prolong the QT interval. This study examines a nonparametric regression model
      (Loess Smoother) to adjust the QT interval for differences in heart rate, with an
      improved fitness over a wide range of heart rates. METHODS: 240 sets of (QT, RR)
      observations collected from each of 8 conscious and non-treated beagle dogs were
      used as the materials for investigation. The fitness of the nonparametric
      regression model to the QT-RR relationship was compared with four models
      (individual linear regression, common linear regression, and Bazett's and
      Fridericia's correlation models) with reference to Akaike's Information Criterion
      (AIC). Residuals were visually assessed. RESULTS: The bias-corrected AIC of the
      nonparametric regression model was the best of the models examined in this study.
      Although the parametric models did not fit, the nonparametric regression model
      improved the fitting at both fast and slow heart rates. DISCUSSION: The
      nonparametric regression model is the more flexible method compared with the
      parametric method. The mathematical fit for linear regression models was
      unsatisfactory at both fast and slow heart rates, while the nonparametric
      regression model showed significant improvement at all heart rates in beagle
      dogs.

PMID- 16297643
TI  - Autogenous options in secondary and tertiary access for haemodialysis.
AB  - OBJECTIVES: The world's haemodialysis population is growing rapidly so that in
      2006, some 1.5 million interventions will be needed for access placement,
      revision and maintainance. Secondary and tertiary arteriovenous fistulas are
      becoming an integral part of vascular access especially in the elderly, comorbid
      population. METHODS: Venous conduits may have a more favourable outcome with
      fewer complications and revisions in comparison with accesses using prosthetic
      implants. Innovative surgical techniques, including vein transposition,
      translocation and elevation may add to this philosophy of creating exclusively
      autogenous vascular access.

PMID- 16297642
TI  - The in vitro effects of dehydroepiandrosterone on chondrocyte metabolism.
AB  - OBJECTIVE: To investigate the in vitro effects of dehydroepiandrosterone (DHEA)
      on neonatal rat chondrocytes. DESIGN: Chondrocytes isolated from neonatal rat
      cartilage were cultured in three-dimensionally agarose beads and were treated
      with DHEA. METHODS: Primary culture of chondrocytes was harvested from newborn
      Wistar rats. The DHEA effects on chondrocyte activities were evaluated by
      analyzing chondrocyte proliferation, matrix protein synthesis, gene expressions
      of collagen, matrix metalloproteinase-1, -3 and -13 (MMP-1, -3 and -13), and
      cyclooxygenase-2 (COX-II), and protein synthesis of interleukin-6 (IL-6),
      prostaglandin E2 (PGE2) and tissue inhibitor of metalloproteinase-1 (TIMP-1).
      RESULTS: The DHEA treatment did affect chondrocyte proliferation and
      glycosaminoglycan (GAG) synthesis. DHEA suppressed the expression of MMP-1, -3
      and -13 genes and PGE2 protein synthesis enhanced by lipopolysaccharide (LPS)
      while the COX-II and inducible nitric oxide synthase (iNOS) gene expressions were
      down-regulated by DHEA. CONCLUSIONS: Our study demonstrates that DHEA has an
      ability to modulate the imbalance between MMPs and PGE2 in the neonatal
      chondrocytes which suggest that it has a potential protective role against
      articular cartilage damage.

PMID- 16297644
TI  - Radiological intervention to maintain vascular access.
AB  - Stenoses and thromboses of dialysis grafts and fistulae are common problems in
      patients with end stage renal disease (ESRD). Timely recognition and treatment of
      access-related complications are essential to achieve long-term access function.
      Minimally invasive percutaneous interventions are techniques of growing
      importance for the interventional community. While stenoses can typically be
      treated by balloon angioplasty (PTA), thrombotic lesions may necessitate the
      combination of mechanical devices and/or thrombolytic agents with ancillary PTA.
      In this article, interventional treatments for the failing arteriovenous (AV)
      access are presented and reviewed.

PMID- 16297645
TI  - 'Pole test' measurements in critical leg ischaemia.
AB  - BACKGROUND: For the quantification of critical limb ischaemia (CLI) most vascular
      surgery units use sphygmo-manometric and transcutaneous oxygen pressure (TcPO2)
      measurements. However, measurements obtained by cuff-manometry can be
      overestimated especially in diabetic patients because of medial calcification
      that makes leg arteries less compressible. TcPO2 measurements present a
      considerable overlap in the values obtained for patients with different degrees
      of ischaemia and its reproducibility has been questioned. Arterial wall stiffness
      has less influence on the pole test, based on hydrostatic pressure derived by leg
      elevation, and this test seems to provide a reliable index of CLI. OBJECTIVE: The
      objective of this study was to evaluate the pole pressure test for detection of
      critical lower limb ischaemia, correlating results with cuff-manometry and
      transcutaneous oxygen pressure. DESIGN: University hospital-prospective study.
      MATERIALS AND METHODS: Seventy-four patients (83 legs) with rest pain or gangrene
      were evaluated by four methods: pole test, cuff-manometry, TcPO2 and
      arteriography. CLI was present if the following criteria were met: (a) important
      arteriographic lesions+rest pain with an ankle systolic pressure (ASP) < or = 40
      mmHg and/or a TcPO2 < or = 30 mmHg, or (b) important arteriographic
      lesions+tissue loss with an ASP < or = 60 mmHg and/or a TcPO2 < or = 40 mmHg.
      Fifty-seven lower limbs met the criteria for CLI. RESULTS: Measurements obtained
      by cuff-manometry were significantly higher to those obtained by pole test (mean
      pressure difference: 40 mmHg, p<0.001). The difference between the two methods
      remained statistically significant for both diabetics (50.73, p<0.001) and non
      diabetics (31.46, p<0.001). Mean TcPO2 value was 15.51 mmHg and there was no
      important difference between patients with and without diabetes. Overall, there
      was a correlation between sphygmomanometry and pole test (r = 0.481). The
      correlation persisted for patients without diabetes (r = 0.581), but was not
      evident in patients with diabetes. Correlation between pole test and TcPO2 was
      observed only for patients with diabetes (r = 0.444). There was no correlation
      between cuff-manometry and TcPO2. The pole test offered an accuracy of 88% for
      the detection of CLI. The sensitivity of this test was 95% and the specificity
      73%.

PMID- 16297646
TI  - Allometric estimation of metabolic rate from heart rate in penguins.
AB  - Studies of the relationship between heart rate (f(H)) and rate of oxygen
      consumption (V(.) (O(2))), which are then used to predict field metabolic rate,
      frequently fail to incorporate body mass as a predictive variable. This is a
      potentially important omission in the study of animals whose body mass fluctuates
      substantially during their annual cycle. In an attempt further to improve
      estimates of field metabolic rate from f(H), we re-evaluated data on M(b), f(H)
      and V(.) (O(2)) from previous studies of macaroni penguins (Eudyptes
      chrysolophus) and king penguins (Aptenodytes patagonicus) and derived a new
      relationship to integrate these three quantities. This relationship is at least
      as accurate and precise as previously determined relationships. We applied this
      same principle to published data on 11 of the 20 recognised penguin taxa to
      derive a relationship to predict V(.) (O(2)) from f(H) and M(b) in penguins of
      any species. This result has interesting implications in terms of reducing the
      logistical burden in studies of field metabolic rate.

PMID- 16297648
TI  - [Quality control: sensitivity of the indirect antiglobulin test by filtration].
AB  - For ten years, the working party of immunohaematology of the French Society of
      Blood Transfusion organizes a quality control. After the modification of the law
      about the realization of erythrocyte typing and detection of unexpected red cell
      allo-antibodies, the quality control was performed in order to determine the
      sensitivity of the indirect antiglobulin test by filtration with a standard anti
      RH1(D) produces by the National Reference Center of Blood Groups.

PMID- 16297647
TI  - Differentiation of long-chain fatty acid oxidation disorders using alternative
      precursors and acylcarnitine profiling in fibroblasts.
AB  - The differentiation of carnitine-acylcarnitine translocase deficiency (CACT) from
      carnitine palmitoyltransferase type II deficiency (CPT-II) and long-chain 3
      hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency from mitochondrial trifunctional
      protein deficiency (MTP) continues to be ambiguous using current acylcarnitine
      profiling techniques either from plasma or blood spots, or in the intact cell
      system (fibroblasts/amniocytes). Currently, enzyme assays are required to
      unequivocally differentiate CACT from CPT-II, and LCHAD from MTP. Over the years
      we have studied the responses of numerous FOD deficient cell lines to both even
      and odd numbered fatty acids of various chain lengths as well as branched-chain
      amino acids. In doing so, we discovered diagnostic elevations of unlabeled
      butyrylcarnitine detected only in CACT deficient cell lines when incubated with a
      shorter chain fatty acid, [7-2H3]heptanoate plus l-carnitine compared to the
      routinely used long-chain fatty acid, [16-2H3]palmitate. In monitoring the
      unlabeled C4/C5 acylcarnitine ratio, further differentiation from ETF/ETF-DH is
      also achieved. Similarly, incubating LCHAD and MTP deficient cell lines with the
      long-chain branched fatty acid, pristanic acid, and monitoring the C11/C9
      acylcarnitine ratio has allowed differentiation between these disorders. These
      methods may be considered useful alternatives to specific enzyme assays for
      differentiation between these long-chain fatty acid oxidation disorders, as well
      as provide insight into new treatment strategies.

PMID- 16297649
TI  - Surface-associated material from Porphyromonas gingivalis stimulates the release
      of nitric oxide by inducing expression of inducible nitric oxide synthase.
AB  - The purpose of this study was to examine the effects of surface-associated
      material (SAM) from Porphyromonas gingivalis, a major cause of inflammatory
      periodontal disease, on the production of nitric oxide (NO) and expression of
      inducible nitric oxide synthase (iNOS) in the murine macrophage cell line
      RAW264.7. We also attempted to throw light on the signaling mechanisms involved
      in P. gingivalis SAM-induced NO production. SAM from P. gingivalis 381 was
      obtained by saline extraction. NO production was assayed by measuring the
      accumulation of nitrite in culture supernatants. Western blot analysis of iNOS
      and analysis of reverse transcription-polymerase chain reaction (RT-PCR) products
      were carried out. We found that P. gingivalis SAM can induce iNOS expression and
      stimulate the release of NO without additional stimuli and demonstrated an
      important role of the transcription factor NF-kappaB and microtubule
      polymerization in NO production. The production of NO required L-arginine,
      protein tyrosine kinase, and protein kinase C. The ability of P. gingivalis SAM
      to promote the production of NO may be important in the pathogenesis of
      inflammatory periodontal disease.

PMID- 16297650
TI  - Shigella and Salmonella: death as a means of survival.
AB  - Shigella and Salmonella kill host cells and trigger inflammatory responses by
      mechanisms that are not fully understood. The goal of this review is to
      reevaluate key observations reported over the past 15 years and, whenever
      possible, to provide a chronological perspective as to how our understanding of
      the pathways by which Shigella and Salmonella kill host cells has evolved.

PMID- 16297651
TI  - COX-2 inhibition affects growth rate of Chlamydia muridarum within epithelial
      cells.
AB  - Chlamydiae alter apoptosis of host target cells, which regulates their growth.
      Cyclooxygenase-2 (COX-2), the rate-limiting enzyme for prostaglandin E2 (PGE2)
      production, modulates epithelial cell survival. We addressed whether endogenous
      PGE2 alters chlamydial growth or apoptosis of epithelial cells infected with
      Chlamydia muridarum. PGE2 is secreted by infected host cells in the genital tract
      (GT). Using immunohistochemical techniques, we found that COX-2 enzyme was
      localized to epithelial cells in the GT in vivo. Pellets of the COX-2 enzyme
      inhibitor, NS-398, and placebo were implanted in mice subcutaneously and released
      a constant amount of these chemicals throughout the infection. NS-398-treated
      mice were found to exhibit 10-fold lower bacterial load than the placebo group on
      day 3 post infection, suggesting disruption of the chlamydial developmental
      cycle. To prove this, the human lung adenocarcinoma cell line A549 was then
      infected with different MOIs of C. muridarum in the presence of multiple
      concentrations of NS-398 in vitro. There was no difference in inclusion forming
      units (IFUs) between NS-389-treated and untreated cells. We also found no
      alterations in C. muridarum IFUs in A549 cells transfected with a 2.0 kb cDNA
      fragment of human COX-2 cloned in the sense (S) or anti-sense (AS) orientation.
      However, the inclusion size was reduced and the number of EB was significantly
      diminished during reinfection in AS-transfected cells. In addition, the absence
      of COX-2 did not significantly modify apoptosis in infected cells. In total, COX
      2 deficiency reduces the infectious burden in vivo and may modulate transmission
      of the organism.

PMID- 16297652
TI  - Calpain 1-gamma filamin interaction in muscle cells: a possible in situ
      regulation by PKC-alpha.
AB  - Calpains are a family of calcium-dependent cysteine-proteases involved in
      cytoskeleton remodelling and muscle differentiation. In a recent study, we
      observed the presence of calpain 1 in the muscle contractile apparatus and
      specifically in the N1- and N2-lines. This calpain isoform was found to be
      involved in the degradation of muscle fibres via proteolysis of key proteins in Z
      disk and costameric junctions. The goal of this study was to determine whether
      gamma-filamin--a specific muscle isoform of the filamin family--is a calpain 1
      substrate and to characterise this interaction. Gamma-filamin is a major muscle
      architectural protein located in the Z-line and under the sarcolemmal membrane.
      This protein is a component of the chain binding the sarcolemma to the sarcomeric
      structure. In this study, we found that gamma-filamin formed a stable complex in
      vitro and in cells with calpain 1 in the absence of calcium stimulation. We also
      located the binding domains in the C-terminus of gamma-filamin with a cleavage
      site between serine 2626 and serine 2627 in the hinge 2 region. The catalytic (80
      kDa) and regulatory (28 kDa) subunits of calpain 1 are both involved in high
      affinity binding at gamma-filamin. Moreover, we showed that phosphorylation of
      the filamin C-terminus domain by PKC alpha protected gamma-filamin against
      proteolysis by calpain 1 in COS cells. Stimulation of PKC activity in myotubes,
      prevented gamma-filamin proteolysis by calpain and resulted in an increase in
      myotube adhesion.

PMID- 16297654
TI  - Cross-talk between IGF-I and TGF-beta signaling pathways.
AB  - Insulin-like growth factor-I (IGF-I) has gained broad recognition as an important
      survival factor for epithelial cells in numerous tissues. The IGF-I receptor
      signaling pathway is deregulated in the majority of carcinomas, and such
      deregulation has also been reported to be tightly associated with enhanced tumor
      progression and metastasis. One of the key proteins that transduces IGF-I signals
      and is phospho-activated downstream of the IGF-I receptor, is the non-receptor
      serine/threonine kinase proto-oncogene protein kinase B (PKB, also known as Akt).
      This kinase serves as a major molecular node to control the function of many cell
      survival and death proteins through phosphorylation-mediated protein
      modification. The end result of the activation of Akt is enhanced cell survival
      and proliferation, pre-requisites for malignant transformation. Recent studies
      show that IGF-I signals cross-talk at multiple levels with various components of
      the TGF-beta signaling pathway, which depending on context may function either as
      tumor suppressor or as tumor promoter. Thus, a better understanding of how the
      IGF-I and TGF-beta signaling pathways are mutually interconnected is likely to
      unveil novel targets for the therapeutic intervention of many cancers.

PMID- 16297655
TI  - Agrobacterium is not alone: gene transfer to plants by viruses and other
      bacteria.
AB  - Agrobacterium-mediated genetic transformation is the most widely used technology
      for obtaining the overexpression of recombinant proteins in plants. However,
      complex patent issues related to the use of Agrobacterium as a tool for plant
      genetic engineering and the general requirement of establishing transgenic plants
      can create obstacles in using this technology for speedy research and development
      and for agricultural improvements in many plant species. Recent studies
      addressing these issues have shown that virus-based vectors can be efficiently
      used for high transient expression of foreign proteins in transfected plants and
      that non-Agrobacterium bacterial species can be used for the production of
      transgenic plants, laying the foundation for alternative tools for future plant
      biotechnology.

PMID- 16297653
TI  - In Saccharomyces cerevisiae an unbalanced level of tyrosine phosphorylation down
      regulates the Ras/PKA pathway.
AB  - The role of tyrosyl phosphorylation/dephosphorylation in the budding yeast
      Saccharomyces cerevisiae, whose genome does not encode typical tyrosine kinases,
      has long remained elusive. Nevertheless, several protein kinases phosphorylating
      poly(TyrGlu) substrates have been identified. In this work, we use the expression
      of the low molecular weight tyrosine phosphatase Stp1 from the distantly related
      yeast Schizosaccharomyces pombe, as a tool to investigate whether an unbalanced
      level of protein tyrosine phosphorylation affects S. cerevisiae growth and
      metabolism. We correlate the previously reported down-regulation of the
      phosphotyrosine level brought about by overexpression of Stp1 with a large number
      of phenotypes indicative of down-regulation of the Ras pathway. These phenotypes
      include reduction in both glucose- and acidification-induced GTP loading of the
      Ras2 protein and cAMP signaling, impaired growth on a non-fermentable carbon
      source, alteration of cell cycle parameters, delayed recovery from nitrogen
      starvation, increased heat-shock resistance, attenuated pseudohyphal and invasive
      growth. Genetic data suggest that Stp1 acts either at, or above, the level of
      Ras2, possibly on the Ira proteins. Consistently, Stp1 was found to bind to
      immunoprecipitated Ira2. Since a catalytically inactive mutant form of Stp1
      (Stp1(C11S)) effectively binds to Ira2 without producing any effect on yeast
      physiology, we conclude that down-regulation of the Ras pathway by Stp1 requires
      its phosphatase activity. In conclusion, our data suggest a possible cross-talk
      between tyrosine phosphorylation and the Ras pathway in yeast.

PMID- 16297656
TI  - Golden Rice--five years on the road--five years to go?
AB  - Provitamin A accumulates in the grain of Golden Rice as a result of genetic
      transformation. In developing countries, where vitamin A deficiency prevails,
      grain from Golden Rice is expected to provide this important micronutrient
      sustainably through agriculture. Since its original production, the prototype
      Golden Rice has undergone intense research to increase the provitamin A content,
      to establish the scientific basis for its carotenoid complement, and to better
      comply with regulatory requirements. Today, the current focus is on how to get
      Golden Rice effectively into the hands of farmers, which is a novel avenue for
      public sector research, carried out with the aid of international research
      consortia. Additional new research is underway to further increase the
      nutritional value of Golden Rice.

PMID- 16297657
TI  - Electron spin resonance assay of ascorbyl radical generation in mouse hippocampal
      slices during and after kainate-induced seizures.
AB  - As an index of oxidative status, we analyzed ascorbyl radical generation during
      and after kainate-induced seizures in mouse hippocampus, using an ESR
      spectrometer equipped with a special tissue-type quartz cell. A specific doublet
      ESR spectrum was observed after seizures, and the g value and the hyperfine
      coupling constant (hfcc) of the spectrum were identical with those of ascorbyl
      radical itself. Antiepileptic zonisamide inhibited the generation of ascorbyl
      radical accompanying the seizures.

PMID- 16297658
TI  - Molecular structure of 2-(hydroxyimino)propanohydroxamic acid in solid state and
      DMSO solution.
AB  - The 1H and 13C NMR spectra of 2-(hydroxyimino)propanohydroxamic acid (hpha) were
      measured in DMSO-d6 solution. The set of several monomeric structures along with
      the cluster of H-bonded hpha with three DMSO molecules were proposed to fit the
      experimental data. The calculated chemical shifts [B3LYP/6-311++G(d,p)] strongly
      suggested the formation of the cluster in which all the labile protons were H
      bonded to the solvent molecules. The comparison between experimental and
      calculated Raman spectra of hpha in DMSO also suggested that in these conditions
      the investigated compound forms the proposed cluster rather than dimers.
      According to our calculations [B3LYP/6-31+G(d)] this cluster was energetically
      stabilized (84-106 kJ mol-1) compared to postulated dimeric structures. On the
      other hand, formation of dimers was proposed to be present for hpha in solid
      state. The comparison of the vibrational data (IR, RS) with the computed harmonic
      frequencies of three most probable dimers [B3LYP/6-31+G(d)] suggested that the
      dimer in which molecules adopted the zEe-keto form and were linked by two
      symmetric, almost linear H-bonds between the carbonyl oxygen atoms and the
      hydroxamic O-H protons was the predominant species of hpha in the solid state.
      Thus, the structures of hpha in solid state and DMSO solution appeared to be
      different.

PMID- 16297659
TI  - Complete response by a combination of 5-fluorouracil and interferon-alpha
      chemotherapy for lung metastasis of hepatocellular carcinoma after hepatic
      resection with portal and hepatic vein tumor thrombectomy.
AB  - A 75-year-old female was admitted to our hospital and diagnosed with
      hepatocellular carcinoma (HCC). Computed tomography (CT) revealed a liver tumor
      with tumor thrombi in the portal trunk and main hepatic vein, as well as small
      lung metastases. The patient had good liver function with no sign of hepatitis B
      or C infection. She underwent right trisectionectomy of the liver with tumor
      thrombectomy. Intrahepatic recurrence and progression of lung metastases were
      observed 4 months later. Intrahepatic recurrent tumors were treated with
      transcatheter arterial chemoembolization (TACE), and lung metastases were treated
      with systemic combination chemotherapy of 5-fluorouracil (5FU) and interferon
      alpha (IFN-alpha). Computed tomography showed no viable lesions in the liver and
      lung 6 months after these treatments. The patient has been disease free for 18
      months. Prognosis is poor for patients with hepatocellular carcinoma with portal
      vein tumor thrombus (PVVT) or extrahepatic metastasis. This systemic combination
      chemotherapy with 5-fluorouracil and interferon-alpha might be effective for
      patients with good liver function when intrahepatic lesions are well controlled
      by multidisciplinary treatments, including hepatic resection with tumor
      thrombectomy.

PMID- 16297660
TI  - Genipin prevents fulminant hepatic failure resulting in reduction of lethality
      through the suppression of TNF-alpha production.
AB  - Genipin is a metabolite derived from the herbal medicine Inchinko-to. Little is
      known about the mechanism of genipin action on acute liver injury through
      inflammatory cytokines. We examined the effects of genipin on production of TNF
      alpha in vivo and in vitro. Mice were given GalN/LPS with or without genipin
      treatment. All mice not given genipin died within 12h. But in mice given genipin,
      8 of 15 mice survived for 24h after GalN/LPS administration. Histologically,
      hepatic necrosis and inflammatory cells infiltration were significantly slight in
      mice given genipin. Serum AST and ALT activity were significantly lower in mice
      given genipin. Serum and liver homogenate TNF-alpha levels were significantly
      lower in mice given genipin. However, in IL-6 and IL-1beta, there were no
      significant differences in mice given and not given genipin. TNF-alpha, NF-kappaB
      activation and TNF-alpha mRNA expression in a cultured mouse macrophage-like cell
      line J774.1 were significantly suppressed by genipin administration. In
      conclusion, the present findings suggest that genipin, a metabolite derived form
      the herbal medicine Inchinko-to improved acute liver dysfunction by suppressive
      effect of TNF-alpha production.

PMID- 16297661
TI  - Have we cut ourselves too short in mapping CTL epitopes?
AB  - MHC class I molecules generally present peptides of eight to ten amino acids;
      however, peptides of 11-14 residues can also elicit dominant cytotoxic T
      lymphocyte responses, sometimes at the expense of overlapping shorter peptides.
      Although long-bulged epitopes are considered to represent a barrier for T cell
      receptor recognition, recent structural data reveal how these super-bulged
      peptides are engaged while simultaneously maintaining MHC restriction. We propose
      that algorithms widely used to predict class I-binding peptides should now be
      broadened to include peptides of over ten residues in length.

PMID- 16297662
TI  - Family functioning assessed by family members in Finnish families of heart
      patients.
AB  - BACKGROUND: The role of family is central to the wellbeing and health of
      individuals. Family attitudes, habits and routines affect the way individuals
      promote their health. Family functioning and family health are threatened when
      one family member develops heart disease. AIMS: The aim of the study was to
      describe family functioning and to ascertain factors related to family
      functioning of families with heart patient as assessed by family members.
      METHODS: Data collection was done using a questionnaire (FAFHES) in 2000. The
      sample consisted of 161 family members of patients receiving treatment on two
      medical wards. The data were analysed by means and tested by parametric and non
      parametric tests. The multivariate method used was stepwise regression analysis.
      RESULTS: The better the family values were materialized and the greater the
      family's contribution to family health, the better the family's functioning is.
      Concrete aid was also related to family health. The more concrete aid the family
      received from nurses, the better family functioning is. When the background
      variables were included, values and activities remained in the model, but two new
      variables explained family functioning: family member's age and knowledge of
      health issues. The older the family member is and the better the knowledge in the
      family is, the better is family functioning. CONCLUSION: Family functioning of
      families with heart patients can be supported and developed by family nursing,
      e.g. concrete aid from nurses. Other aspects of support, e.g. consideration of
      family member's age and knowledge of health issues also need to be further
      considered and studied as the basis of care.

PMID- 16297663
TI  - Restenosis after percutaneous coronary intervention (PCI): experiences from the
      patients' perspective.
AB  - BACKGROUND: PCI has been established as an effective treatment for coronary
      artery disease. Restenosis is a recurrence of a significant narrowing in the
      treated vessel. Although a part of the investigative and research funding is
      invested in the prevention and resolving the restenosis problem, little is known
      about its clinical significance apart from further revascularisation. AIM: The
      intention of this study was to clarify the patients perspective of what it means
      to suffer from documented restenosis after PCI. METHOD: Patients interviewed had
      undergone PCI. Data collection and analysis was done simultaneously according to
      Grounded Theory methodology and continued until new interviews provided no
      additional information. RESULTS: "Living with uncertainty" was identified as the
      core category, and the central focus in the data explains what it means to
      patients' to suffer from restenosis. The core category was further illuminated in
      four additional categories labelled "fighting for access to care", "moderating
      health threats", "trying to understand" and "controlling relatives anxiety".
      CONCLUSION: Patients' perceptions of illness and illness-related events, such as
      symptoms, diagnosis, treatment and prognosis, are considerably affected by
      uncertainty. This infiltrates their struggle to acquire the care needed, their
      endeavour to comprehend and moderate health threats, and caring for their family.

PMID- 16297664
TI  - Genotype/phenotype correlations in X-linked agammaglobulinemia.
AB  - No clear genotype/phenotype correlations have been established in patients with X
      linked agammaglobulinemia (XLA). To determine if the specific mutation in Btk
      might be one of the factors that influences the severity of disease or if
      polymorphic variants in Tec, a cytoplasmic tyrosine kinase that might substitute
      for Btk, could contribute to the clinical phenotype, we examined the age at
      diagnosis, the percentage of peripheral blood B cells and the plasma IgM in a
      large group of patients with XLA. The results demonstrated that polymorphic
      variants in Tec were not correlated with phenotypic markers; however, the
      specific mutation in Btk did influence disease severity. Mutations that
      conceivably allow the production of some Btk, amino acid substitutions or splice
      defects that occur at conserved but not invariant sites in the splice consensus
      sequence were associated with older age at diagnosis, a higher percentage of B
      cells in the peripheral circulation and higher concentrations of plasma IgM.

PMID- 16297665
TI  - Genetic analysis and functional evaluation of the C/T(-318) and A/G(-1661)
      polymorphisms of the CTLA-4 gene in patients affected with Graves' disease.
AB  - In this study, we evaluated the A/G(-1661), C/T(-318), A/G49 and A/G6230 single
      nucleotide polymorphisms (SNPs) of the cytotoxic T lymphocyte antigen 4 (CTLA-4)
      gene for association with Graves' disease (GD) in 126 Russian simplex families.
      The conditional TDT analysis revealed significant overtransmission of the A(
      1661)G(-318) haplotype (P = 0.033) and undertransmission of the GT haplotype (P =
      0.0043) from parents homozygous for both +49 and +6230 polymorphisms. Parents
      homozygous for both (-1661) and (-318) markers significantly overtransmitted the
      G49G6230 haplotype (P = 0.0013) and undertransmitted the AG haplotype (P = 0.035)
      to affected offspring. This suggests in favor of the independent genetic effects
      of the 3' and 5'ends of CTLA-4 in conferring the susceptibility to GD. Both SNPs
      located at the 5' untranslated region of CTLA-4 were functionally analyzed using
      the luciferase reporter assay. We observed differential activation of the C/T(
      318) promoter variant when Jurkat T cells and HeLa cells were cotransfected with
      a plasmid expressing lymphoid enhancing factor 1 (LEF1) and various CTLA-4
      promoter constructs. The (-318) SNP modifies a putative binding site for LEF1 so
      that it alters the stimulating effect of LEF1 on the expression ability of the
      CTLA-4 promoter. The (-1661) dimorphism modifies a potential binding site for
      myocyte enhancer factor 2 (MEF2). No significant correlation between the (-1661)
      SNP and MEF2 activity in cotransfection experiments was found. Observed data help
      for further understanding a functional role of CTLA-4 promoter polymorphisms in
      the pathogenic mechanism of GD.

PMID- 16297666
TI  - Recombinant adenovirus vaccines can successfully elicit CD8+ T cell immunity
      under conditions of extreme leukopenia.
AB  - We have examined the efficacy of vaccination with recombinant adenovirus under
      conditions of extreme leukopenia in lethally irradiated mice reconstituted with
      autologous bone marrow. The expansion of antigen-specific CD8(+) T cells
      following immunization of lethally irradiated hosts paralleled the recovery of
      total CD8(+) T cells. Surprisingly, the numbers of antigen-specific CD8(+) T
      cells in lethally irradiated mice beyond 6 weeks postimmunization were comparable
      to the numbers found in nonirradiated controls. CD8(+) T cells elicited in the
      lethally irradiated hosts were functionally indistinguishable from those elicited
      in normal hosts. Antigen expression and presentation persisted for a longer
      period of time in the draining lymph nodes of irradiated mice compared to those
      of nonirradiated animals, suggesting that antigen presentation mechanisms were
      intact during the reconstitution period. Experiments employing allogeneic bone
      marrow demonstrated that radioresistant host antigen-presenting cells were
      responsible for antigen presentation during the process of immune reconstitution.
      These results demonstrate clear compatibility of adenovirus vaccines and
      cytotoxic therapy. Furthermore, these observations provide novel insights into
      the mechanisms of CD8(+) T cell activation following adenovirus immunization.

PMID- 16297669
TI  - Determination of celecoxib in human plasma and breast milk by high-performance
      liquid chromatographic assay.
AB  - A rapid and simple HPLC assay was developed for the determination of celecoxib in
      human plasma and breast milk. After proteins were precipitated with acetonitrile,
      celecoxib was resolved on a C18 column and detected by UV detection at 254 nm.
      Standard curves were linear over the concentration range 10-2000 microg/L
      (r(2)>0.99). Bias was </=+/-15% from 20 to 2000 microg/L in both matrices, intra-
      and inter-day coefficients of variation (imprecision) were <10%, and the limit of
      quantification was 10 microg/L.

PMID- 16297667
TI  - BCR/ABL modifies the kinetics and fidelity of DNA double-strand breaks repair in
      hematopoietic cells.
AB  - The oncogenic BCR/ABL tyrosine kinase facilitates the repair of DNA double-strand
      breaks (DSBs). We find that after gamma-irradiation BCR/ABL-positive leukemia
      cells accumulate more DSBs in comparison to normal cells. These lesions are
      efficiently repaired in a time-dependent fashion by BCR/ABL-stimulated non
      homologous end-joining (NHEJ) followed by homologous recombination repair (HRR)
      mechanisms. However, mutations and large deletions were detected in HRR and NHEJ
      products, respectively, in BCR/ABL-positive leukemia cells. We propose that
      unfaithful repair of DSBs may contribute to genomic instability in the
      Philadelphia chromosome-positive leukemias.

PMID- 16297668
TI  - Quantification of six herbicide metabolites in human urine.
AB  - We developed a sensitive, selective and precise method for measuring herbicide
      metabolites in human urine. Our method uses automated liquid delivery of internal
      standards and acetate buffer and a mixed polarity polymeric phase solid phase
      extraction of a 2 mL urine sample. The concentrated eluate is analyzed using high
      performance liquid chromatography-tandem mass spectrometry. Isotope dilution
      calibration is used for quantification of all analytes. The limits of detection
      of our method range from 0.036 to 0.075 ng/mL. The within- and between-day
      variation in pooled quality control samples range from 2.5 to 9.0% and from 3.2
      to 16%, respectively, for all analytes at concentrations ranging from 0.6 to 12
      ng/mL. Precision was similar with samples fortified with 0.1 and 0.25 ng/mL that
      were analyzed in each run. We validated our selective method against a less
      selective method used previously in our laboratory by analyzing human specimens
      using both methods. The methods produced results that were in agreement, with no
      significant bias observed.

PMID- 16297670
TI  - Biochemical characterization of the class B acid phosphatase (AphA) of
      Escherichia coli MG1655.
AB  - The AphA enzyme of Escherichia coli, a molecular class B periplasmic phosphatase
      that belongs to the DDDD superfamily of phosphohydrolases, was purified and
      subjected to biochemical characterization. Kinetic analysis with several
      substrates revealed that the enzyme essentially behaves as a broad-spectrum
      nucleotidase highly active on 3'- and 5'-mononucleotides and
      monodeoxynucleotides, but not active on cyclic nucleotides, or nucleotides di-
      and triphosphate. Mononucleotides are degraded to nucleosides, and AphA
      apparently does not exhibit any nucleotide phosphomutase activity. However, it
      can transphosphorylate nucleosides in the presence of phosphate donors. Kinetic
      properties of AphA are consistent with structural data, and suggest a role for
      the hydrophobic pocket present in the active site crevice, made by residues Phe
      56, Leu71, Trp77 and Tyr193, in conferring preferential substrate specificity by
      accommodating compounds with aromatic rings. AphA was inhibited by several
      chelating agents, including EDTA, EGTA, 1,10-phenanthroline and dipicolinic acid,
      with EDTA being apparently the most powerful inhibitor.

PMID- 16297671
TI  - Reflux rising! An essay on witnessing a disease in evolution.
AB  - BACKGROUND AND AIM: The prevalence of gastro-oesophageal reflux disease is
      thought to be rising but supporting evidence is sparse. We assessed trends from
      data prospectively collected over 25 years at our centre which serves Rotherham's
      250000 population. PATIENTS AND METHODS: Detailed computerised records have been
      kept of all patients investigated for upper gastrointestinal symptoms.
      DEFINITION: Erosive oesophagitis=endoscopy-verified erosive changes. Non-erosive
      reflux=heartburn+/-regurgitation but normal endoscopy. Gastro-oesophageal reflux
      disease=erosive oesophagitis+non-erosive reflux, i.e. total. RESULTS: The data,
      presented in 5-year time periods spanning 1977-2001, showed four major changing
      trends. (1) The numbers with newly diagnosed gastro-oesophageal reflux disease
      rose markedly, affecting both erosive oesophagitis and non-erosive reflux. Gastro
      oesophageal reflux disease: n=714; 1587; 2381; 3812; 3880. (2) The proportion of
      women affected rose from 0.36 to 0.82. (3) Gastro-oesophageal reflux disease
      patients were older than the general population; the mean age at presentation
      rose from 48.0 to 53.5 years. (4) Presentation with haemorrhage (percentage of
      erosive oesophagitis) rose from 5.2% to 10.9% but, as with stricture (around 4%),
      remained uncommon. Throughout, few (4.4%) changed from non-erosive reflux to
      erosive oesophagitis. CONCLUSION: The marked increase in gastro-oesophageal
      reflux disease cannot be accounted for by greater awareness alone for the
      demographic profile has changed, or by misclassification as erosive oesophagitis
      was diagnosed on endoscopic appearances. The dramatic five-fold increase in
      gastro-oesophageal reflux disease is a new phenomenon, perhaps an example of a
      disease in evolution.

PMID- 16297672
TI  - Does depression symptomatology affect medication compliance during the first
      weeks of anti-HCV therapy in intravenous drug users?
AB  - BACKGROUND: Psychological adverse effects in intravenous drug users represent a
      challenge in the management of anti-HCV therapy. AIMS: To evaluate the depressive
      symptoms during the first weeks of anti-HCV therapy and to assess their impact on
      the early virological response and discontinuation of therapy. SUBJECTS: A
      prospective cohort study of HCV-infected drug addicts on a detoxification program
      at the onset of therapy with peg-interferon and ribavirin. METHODS: A self-report
      screening of depression (Center for Epidemiological Studies-Depression Scale) and
      a questionnaire investigating treatment adherence and the presence of side
      effects were prospectively administered. RESULTS: The mean baseline Center for
      Epidemiological Studies-Depression Scale score of the 43 subjects studied was
      17.3. This value did not worsen significantly after 4 and 12 weeks of therapy. A
      higher depressive score at baseline neither significantly affected the early
      virological response, nor the early treatment discontinuation. Conversely, a
      higher symptoms score (HR 1.33; 95% CI, 1.02-1.71) was associated with a greater
      probability of early treatment discontinuation. CONCLUSIONS: A depressive
      attitude should not be considered a contraindication to the treatment of HCV
      infected drug addicts on the detoxification program in which they are monitored
      by a multidisciplinary team. Effective management of side effects could increase
      the treatment adherence during the first weeks of therapy and increase the
      possibility of an early virological response.

PMID- 16297673
TI  - Memory for melody: infants use a relative pitch code.
AB  - Pitch perception is fundamental to melody in music and prosody in speech. Unlike
      many animals, the vast majority of human adults store melodic information
      primarily in terms of relative not absolute pitch, and readily recognize a melody
      whether rendered in a high or a low pitch range. We show that at 6 months infants
      are also primarily relative pitch processors. Infants familiarized with a melody
      for 7 days preferred, on the eighth day, to listen to a novel melody in
      comparison to the familiarized one, regardless of whether the melodies at test
      were presented at the same pitch as during familiarization or transposed up or
      down by a perfect fifth (7/12th of an octave) or a tritone (1/2 octave). On the
      other hand, infants showed no preference for a transposed over original-pitch
      version of the familiarized melody, indicating that either they did not remember
      the absolute pitch, or it was not as salient to them as the relative pitch.

PMID- 16297674
TI  - Use of phonetic specificity during the acquisition of new words: differences
      between consonants and vowels.
AB  - The present study explores the issue of the use of phonetic specificity in the
      process of learning new words at 20 months of age. The procedure used follows
      Nazzi and Gopnik [Nazzi, T., & Gopnik, A. (2001). Linguistic and cognitive
      abilities in infancy: When does language become a tool for categorization?
      Cognition, 80, B11-B20]. Infants were first presented with triads of perceptually
      dissimilar objects, which were given made-up names, two of the objects receiving
      the same name. Then, word learning was evaluated through object
      selection/categorization. Tests involved phonetically different words (e.g.
      [pize] vs. [mora], Experiment 1), words differing minimally on their onset
      consonant (e.g. [pize] vs. [tize], Experiment 2a), and conditions which had never
      been tested before: non-initial consonantal contrasts (e.g. [pide] vs. [pige],
      Experiment 2b), and vocalic contrasts (e.g. [pize] vs. [pyze]; [pize] vs. [paze];
      [pize] vs. [pizu], Experiments 3a-c). Results differed across conditions: words
      could be easily learnt in the phonetically different condition, and were learnt,
      though to a lesser degree, in both the initial and non-initial minimal consonant
      contrast; however, infants' global performance on all three vocalic contrasts was
      at chance level. The present results shed new light regarding the specificity of
      early words, and raise the possibility of different contributions for vowels and
      consonants in early word learning.

PMID- 16297676
TI  - A systematic, large-scale study of synaesthesia: implications for the role of
      early experience in lexical-colour associations.
AB  - For individuals with synaesthesia, stimuli in one sensory modality elicit
      anomalous experiences in another modality. For example, the sound of a particular
      piano note may be 'seen' as a unique colour, or the taste of a familiar food may
      be 'felt' as a distinct bodily sensation. We report a study of 192 adult
      synaesthetes, in which we administered a structured questionnaire to determine
      the relative frequency and characteristics of different types of synaesthetic
      experience. Our data suggest the prevalence of synaesthesia in the adult
      population is approximately 1 in 1150 females and 1 in 7150 males. The incidence
      of left-handedness in our sample was within the normal range, contrary to
      previous claims. We did, however, find that synaesthetes are more likely to be
      involved in artistic pursuits, consistent with anecdotal reports. We also
      examined responses from a subset of 150 synaesthetes for whom letters, digits and
      words induce colour experiences ('lexical-colour' synaesthesia). There was a
      striking consistency in the colours induced by certain letters and digits in
      these individuals. For example, 'R' elicited red for 36% of the sample, 'Y'
      elicited yellow for 45%, and 'D' elicited brown for 47%. Similar trends were
      apparent for a group of non-synaesthetic controls who were asked to associate
      colours with letters and digits. Based on these findings, we suggest that the
      development of lexical-colour synaesthesia in many cases incorporates early
      learning experiences common to all individuals. Moreover, many of our
      synaesthetes experienced colours only for days of the week, letters or digits,
      suggesting that inducers that are part of a conventional sequence (e.g. Monday,
      Tuesday, Wednesday...; A, B, C...; 1, 2, 3...) may be particularly important in
      the development of synaesthetic inducer-colour pairs. We speculate that the
      learning of such sequences during an early critical period determines the
      particular pattern of lexical-colour links, and that this pattern then
      generalises to other words.

PMID- 16297677
TI  - On what people know about images on mirrors.
AB  - As observed by Gombrich [Gombrich, E. H. (1960). Art and illusion. Oxford:
      Phaidon Press], we confirm that most people are unaware of the size of their own
      image on mirrors. Specifically we have documented the knowledge that people have
      of the size of their own head and of the size of the mirror image of their own
      head. In addition we have explored naive beliefs about how the size of mirror
      images changes with distance. The main pattern of findings is consistent with a
      focus on target distance and a difficulty in factoring the observer's vantage
      point correctly when people reason about the problem. The issue of information
      about vantage point is discussed in relation to other literatures.

PMID- 16297679
TI  - Imaging of spinal trauma.
AB  - Approximately 2% to 3% of blunt trauma victims suffer injury to the spinal column
      each year, often with devastating consequences. This article discusses clinical
      criteria for screening for spinal injury and the increasing roles of
      multidetector CT and MR imaging in the evaluation of spinal trauma. Both CT and
      MR imaging safety issues also are addressed. Lastly, the role of imaging in the
      evaluation of whiplash injury, instability, vascular injury, and delayed
      traumatic sequelae is discussed.

PMID- 16297675
TI  - Auditory attention to frequency and time: an analogy to visual local-global
      stimuli.
AB  - Two priming experiments demonstrated exogenous attentional persistence to the
      fundamental auditory dimensions of frequency (Experiment 1) and time (Experiment
      2). In a divided-attention task, participants responded to an independent
      dimension, the identification of three-tone sequence patterns, for both prime and
      probe stimuli. The stimuli were specifically designed to parallel the local
      global hierarchical letter stimuli of [Navon D. (1977). Forest before trees: The
      precedence of global features in visual perception. Cognitive Psychology, 9, 353
      383] and the task was designed to parallel subsequent work in visual attention
      using Navon stimuli [Robertson, L. C. (1996). Attentional persistence for
      features of hierarchical patterns. Journal of Experimental Psychology: General,
      125, 227-249; Ward, L. M. (1982). Determinants of attention to local and global
      features of visual forms. Journal of Experimental Psychology: Human Perception
      and Performance, 8, 562-581]. The results are discussed in terms of previous work
      in auditory attention and previous approaches to auditory local-global
      processing.

PMID- 16297680
TI  - Imaging of traumatic neurovascular injury.
AB  - Traumatic injury to the major vessels of the head and neck can result in
      potentially devastating neurologic sequelae. Until recently, conventional
      angiography was the primary imaging modality used to evaluate these often
      challenging patients. Advances in cross-sectional imaging have improved the
      ability to screen for these lesions, which have been found to be more common than
      previously thought; however, accepted protocols of imaging evaluation have not
      yet been fully established. This article presents a general approach to the
      patient with suspected neurovascular injury. This includes a discussion of the
      histopathologic spectrum, clinical presentation, mechanisms, radiologic work-up,
      pertinent issues of the most common lesions, and some of the endovascular
      techniques used in their management.

PMID- 16297681
TI  - Modern emergent stroke imaging: pearls, protocols, and pitfalls.
AB  - Stroke remains one of the most important clinical diagnoses for which patients
      are referred to the radiologist for emergent imaging. Timely and accurate imaging
      guides admission from the emergency department or transfer to a hospital with a
      dedicated stroke service, triage to the intensive care unit, anticoagulation,
      thrombolysis, and many other forms of treatment and management. It is important
      to approach each patient's imaging needs logically and tailor each work-up, and
      constantly to review the entire process for potential improvements. Time saved in
      getting an accurate diagnosis of stroke may indeed decrease morbidity and
      mortality. This article discusses the current management of stroke imaging and
      reviews the relevant literature.

PMID- 16297682
TI  - Acute injury to the immature brain with hypoxia with or without hypoperfusion.
AB  - This article reviews the imaging features and evolution of immature brain injury
      caused by hypoxia with or without hypoperfusion in the neonate and young child.
      Clinical presentations and available literature on mechanisms and clinical
      outcomes are discussed. In many of these cases, diffusion-weighted imaging does
      not show the full extent of the injury but detects a pattern of injury that is
      important in guiding clinical care. Awareness of the delayed cell death
      mechanisms is essential to understand diffusion-weighted imaging sensitivity and
      evolution and to provide the most accurate clinical interpretation, especially in
      cases of hypoxia with or without hypoperfusion.

PMID- 16297683
TI  - Update on multiple sclerosis.
AB  - In this article the basic features of the focal MR imaging lesions and the
      underlying pathology are reviewed. Next, the diffuse pathology in the normal
      appearing white and gray matter as revealed by conventional and quantitative MR
      imaging techniques is discussed, including reference to how the focal and diffuse
      pathology may be in part linked through axonal-neuronal degeneration. The MR
      imaging criteria incorporated for the first time into formal clinical diagnostic
      criteria for multiple sclerosis are next discussed. Finally, a discussion is
      provided as to how MR imaging is used in monitoring subclinical disease either
      before or subsequent to initiation of treatment, in identifying aggressive
      subclinical disease, and treatment of nonresponders.

PMID- 16297684
TI  - Imaging of cervical lymph nodes in head and neck cancer: the basics.
AB  - Imaging can identify pathologic cervical adenopathy in a significant number of
      patients with head and neck cancer who have no palpable adenopathy on physical
      examination. This article reviews nodal classification, drainage patterns of
      different head and neck cancers, various cross-sectional imaging features of
      metastatic lymph nodes from head and neck cancer, nodal staging, and certain
      features like extracapsular spread and carotid and vertebral invasion that the
      clinician should know because they have therapeutic and prognostic implications.
      New imaging techniques and the role of fluorodeoxyglucose positron emission
      tomography imaging in recurrent disease are discussed.

PMID- 16297688
TI  - Indications for elective therapeutic third molar removal: the evidence is in.

PMID- 16297689
TI  - De novo bone induction by recombinant human bone morphogenetic protein-2 (rhBMP
      2) in maxillary sinus floor augmentation.
AB  - PURPOSE: This phase II study was designed to evaluate 2 concentrations of
      recombinant human bone morphogenetic protein-2 (rhBMP-2) for safety and efficacy
      in inducing adequate bone for endosseous dental implant in patients requiring
      staged maxillary sinus floor augmentation. MATERIALS AND METHODS: Patients were
      treated with rhBMP-2 (via an absorbable collagen sponge [ACS]), at concentrations
      of 0.75 mg/mL (n = 18), 1.50 mg/mL (n = 17), or with bone graft (n = 13). Bone
      induction was assessed by alveolar ridge height, width, and density measurements
      from computed tomography scans obtained before and 4 months after treatment and 6
      months post-functional loading of dental implants (density only). RESULTS: Mean
      increases in alveolar ridge height at 4 months after treatment were similar among
      the groups; 11.3 mm, 9.5 mm, and 10.2 mm, respectively, in the bone graft, 0.75
      mg/mL, and 1.50 mg/mL rhBMP-2/ACS treatment groups. Mean increases in alveolar
      ridge width (buccal to lingual) at the crest of the ridge were statistically
      different among the treatment groups; 4.7 mm, 2.0 mm, and 2.0 mm, respectively,
      in the bone graft, 0.75 mg/mL, and 1.50 mg/mL treatment groups (P <or= .01 vs
      0.75 mg/mL; P < .01 vs 1.50 mg/mL). At 4 months postoperative new bone density
      was statistically different among the treatment groups; 350 mg/cc, 84 mg/cc, and
      134 mg/cc for the bone graft, 0.75 mg/mL, and 1.50 mg/mL rhBMP-2/ACS treatment
      groups, respectively (P = .003 vs 0.75 mg/mL, P = .0137 vs 1.50 mg/mL, P = .0188;
      1.50 mg/mL vs 0.75 mg/mL). Core bone biopsies obtained at the time of dental
      implant placement confirmed normal bone formation. The proportion of patients who
      received dental implants that were functionally loaded and remained functional at
      36 months post-functional loading was 62%, 67%, and 76% in the bone graft, 0.75
      mg/mL, and 1.50 mg/mL rhBMP-2/ACS treatment groups, respectively. CONCLUSION:
      This study is the first randomized controlled trial demonstrating de novo organ
      tissue growth in humans from a recombinant human protein. rhBMP-2/ACS safely
      induced adequate bone for the placement and functional loading of endosseous
      dental implants in patients requiring staged maxillary sinus floor augmentation.

PMID- 16297690
TI  - Radiographic evaluation of alveolar distraction osteogenesis: analysis of 60
      cases.
AB  - PURPOSE: The aim of this study was to evaluate radiographically the effectiveness
      of alveolar distraction osteogenesis (ADO) technique for vertical reconstruction
      of atrophy alveolar ridges in partially edentulous patients. MATERIALS AND
      METHODS: A total of 60 vertical distraction osteogenesis procedures were
      performed in 55 patients. Two panoramic radiographies were performed in all
      patients, one the day before the beginning of distraction, and one after
      consolidation period, 12 weeks postoperatively. The radiographic analysis
      consisted of obtaining the amount of the vertical bone gain (VBG) in each
      radiography. For this, we obtained initially the magnification factor (MF) of
      each panoramic radiography by dividing the real size (RS) of the activation rod
      among the image size (IS) of the activation rod. After this, to obtain the VGB,
      we measured initially the length of the distracton preactivation (LD1), which
      consisted of the distance between the superior portion of the basal plate and the
      superior portion of the transport plate, multiplying by the MF. Then, we measured
      the length of the distraction postactivation (LD2), using the same method
      described before, in radiographies performed 12 weeks postoperatively. The VBG
      was obtained using the following formula: VBG = LD2 - LD1. The results were
      applied to descriptive statistical analysis. Complications were also investigated
      during all of the treatments. RESULTS: The mean alveolar distraction achieved in
      60 cases was 6.27 mm (range, 0 to 10.83 mm). According to the region treated,
      51.6% were in the posterior mandible (mean VBG, 4.60 mm), 36.66% were in the
      anterior maxilla (mean VBG, 7.46 mm), 8.33% were in the anterior mandible (mean
      VBG, 6.73 mm), and 3.33% were in the posterior maxilla (mean VBG, 6.32 mm). The
      overall rate of complications that compromised the success of the technique was
      8.44%. The increased radiopacity of the distracted region could be observed in
      the 12-week period after surgery. CONCLUSIONS: The ADO technique was demonstrated
      to be an effective tool to treat vertical defects of the alveolar ridge with a
      success rate of 91.66%. Our radiographic analysis seems to be an important tool
      in verifying the technique as well as planning implant placement after ADO.

PMID- 16297691
TI  - Maxilla sinus grafting with marine algae derived bone forming material: a
      clinical report of long-term results.
AB  - PURPOSE: Autogenous bone grafting continues to be considered the gold standard
      for sinus grafting. For the past 15 years the author has used an alternative
      graft material and followed-up the input/output statistic of implants to evaluate
      if this material results similar to the autogenous bone graft. Histomorphometric
      evaluations of graft materials show how much new bone is formed and if the graft
      material is resorbed. MATERIALS AND METHODS: In our study we used a marine
      derived carbonated red algae that is chemically converted into hydroxyapatite
      (HA). This material is distributed worldwide as the Communaute Europeenne
      approved material AlgiPore (Dentsply Friadent, Mannheim, Germany), as the US Food
      and Drug Administration approved material C GRAFT (The Clinician Preference LLC,
      Golden, CO), and the Russian approved material AlgOss (Unexim Co, Moscow,
      Russia). A total of 209 sinus grafts were performed on 118 patients who presented
      with a severely resorbed maxillary alveolar process with 1 to 5 mm (mean, 3.6 mm)
      of remaining bone. The available bone was comparable to Class D bone as described
      by Simion et al. After 6 months implants were placed and 6 months later the
      implants were loaded. RESULTS: From September 5, 1990, to September 1, 2004, the
      author performed 209 sinus grafts on 118 patients. The longest observation period
      of loaded implants in this study is 156 months (13 years). Implant loss was 27
      out of 614 loaded implants (4.4%), showing a survival rate of 95.6%. Smokers and
      women over 50 are included. Although AlgiPore/C GRAFT/AlgOss (ACA) undergoes a
      resorption process, we found only 14% volume loss after 6.4 months compared with
      49.5% after 6 months when autogenous bone was used. CONCLUSION: This
      retrospective study of over 14 years shows once again that the sinus lift
      procedure with grafting of the sinus floor and subsequent implant placement is a
      proven method. This 14-year longitudinal study shows that the marine derived HA
      material ACA in a mixture with approximately 10% autogenous collector bone and
      blood or platelet rich plasma is able to enhance enough new bone in 6 months to
      allow implant osseointegration after 6 more months with a high implant survival
      rate.

PMID- 16297692
TI  - Alveolar width distraction osteogenesis for early implant placement.
AB  - Distraction osteogenesis for correction of horizontal alveolar width deficiency
      was performed for 9 patients by using an alveolar crest widening device. Four
      prototypes were used during the course of the study until a final protocol was
      achieved. Under local anesthesia, a blind crestal osteotomy was carried out with
      minimal periosteal reflection. The horizontal distraction device was placed
      percutaneously. Distraction proceeded from the seventh postoperative day at a
      rate of 0.4 mm/day for 14 to 18 days. Seven to 10 days later, dental implants
      were placed. Distraction osteogenesis occurred in all 9 patients and increased
      alveolar width from 4 to 6 mm. Twenty implants successfully osteointegrated of 21
      placed. Marginal bone resorption was not observed after 12 months' follow-up. The
      advantages of horizontal distraction over block grafting include simultaneous
      expansion of soft tissue, high degree of dimensional stability, abbreviated
      overall treatment time, and no graft requirement.

PMID- 16297693
TI  - Postoperative morbidities following dental care under day-stay general anesthesia
      in intellectually disabled children.
AB  - PURPOSE: The objective of this study was to compare the postoperative morbidities
      for 24 hours following dental care under day-stay general anesthesia using
      sevoflurane or halothane in intellectually disabled children. MATERIALS AND
      METHODS: Eighty-six premedicated patients with intellectual disabilities
      underwent general anesthesia for their dental treatment. They were randomly given
      anesthesia maintained with sevoflurane (2% to 3%) or halothane (1% to 1.5%) after
      receiving inhalation induction either with sevoflurane (8%) or halothane (5%) and
      nitrous oxide in oxygen (50:50). The patients' age, gender, weight, ASA Class,
      type of dental treatment, and duration of anesthesia and operation were recorded
      as well as the time required for recovery (Aldrete Scale) and the length of time
      taken before they were discharged (postanesthetic discharge scoring system) from
      the hospital. Pain and agitation were recorded using a visual analog scale (0 to
      10). Other postoperative morbidities, which include crying, nausea and vomiting,
      bleeding, and drowsiness, were also noted for 24 hours after the operation.
      RESULTS: The most common morbidities during the postoperative 24 hours were
      agitation and pain, and their occurrence was significantly more common in the
      sevoflurane group than in the halothane group (P < .05). The recovery time was
      shorter in the sevoflurane group, but it was not statistically significant. There
      was no difference between the groups in the discharge time. CONCLUSIONS: Apart
      from more postoperative agitation and pain after awakening from sevoflurane, the
      quality of recovery was similar for both sevoflurane and halothane.

PMID- 16297694
TI  - Transoral 2.0-mm locking miniplate fixation of mandibular fractures plus 1 week
      of maxillomandibular fixation: a prospective study.
AB  - PURPOSE: In this study, a 2.0-mm locking miniplate (LMP)/screw system was
      assessed in the treatment of mandibular fractures with a 1-week period of
      maxillomandibular fixation (MMF). PATIENTS AND METHODS: Fifty mandibular
      fractures in 34 patients with a mean of 6.97 days of MMF were included in the
      study. The 2.0-mm LMPs were adapted along Champy's line of ideal osteosynthesis
      and secured with four 8.0-mm locking monocortical screws. All patients were
      followed for a minimum of 6 weeks. The incidence of soft tissue infections,
      nonunion, malunion, malocclusion, osteomyelitis, nerve injury, and tooth damage
      was prospectively assessed. RESULTS: Primary bone healing was achieved in 98% of
      cases. Three complications (6%) were observed. Two minor complications of
      intraoral wound dehiscence and malocclusion were noted. A fibrous nonunion
      requiring 3 additional weeks of MMF was noted. No evidence of malunion,
      osteomyelitis, plate fracture, iatrogenic nerve injuries, or dental injuries was
      noted. CONCLUSIONS: A single 2.0-mm LMP placed along Champy's line of ideal
      osteosynthesis with four 8-mm monocortical locking screws plus 1 week of MMF
      fixation is a reliable and effective treatment modality for mandibular fractures.

PMID- 16297695
TI  - Current diagnosis and transoral surgical treatment of Eagle's syndrome.
AB  - PURPOSE: The purpose of this study was to discuss the current diagnosis of
      Eagle's syndrome and to present our experience in transoral surgical treatment of
      the syndrome. MATERIALS AND METHODS: Nineteen patients with Eagle's syndrome due
      to elongated styloid process were included in this clinical trial. Diagnostic
      work-up also consists of 3-dimensional computed tomography scanning in recent
      cases. Elongated styloid processes were resected via transoral approach under
      general anesthesia. RESULTS: Three-dimensional computed tomography scanning
      depicted how the preoperative estimation of the styloid length correlated with
      the true styloid length measure intraoperatively. No postoperative complications
      were encountered, while the chief symptoms of all patients regressed after
      surgery. CONCLUSIONS: Three-dimensional computed tomography scanning is an
      advanced technique that can measure the definitive length of styloid process and
      takes the physician straightforward to the exact diagnosis. The transoral
      approach is a safe surgical alternative that achieves adequate treatment of
      Eagle's syndrome.

PMID- 16297696
TI  - The role of imaging and surgery in the management of vascular tumors of the
      masseter muscle.
AB  - PURPOSE: Intramuscular vascular malformations are uncommon lesions in the head
      and neck that may mimic salivary gland disease. This study reports on the use of
      various imaging modalities and recommends a surgical approach in the management
      of vascular malformations of the masseter muscle. PATIENTS AND METHODS: This is a
      retrospective study of 7 consecutive patients with vascular tumors of the
      masseter muscle treated in one unit between 1995 and 2004. The age, gender, signs
      and symptoms, imaging methods, and surgical outcome are reported. A previously
      unreported surgical approach is described. RESULTS: All patients had atypical
      swellings in and around the parotid region that were difficult to diagnose on
      plain radiography and computed tomography. Magnetic resonance imaging provides
      accurate three-dimensional images and provisional diagnosis of lesions within the
      masseter muscle. Six of the 7 patients underwent surgery by the recommended
      approach. No patients developed permanent facial weakness following modified
      parotidectomy. No recurrence of the vascular tumors occurred when the recommended
      approach is used. CONCLUSIONS: Magnetic resonance imaging remains the imaging
      modality of choice for the management of tumors of the masseter muscle. The
      extended parotidectomy approach gives good and safe surgical access in the
      management of these uncommon lesions.

PMID- 16297698
TI  - Primary reconstruction of the maxilla following maxillectomy with or without
      sacrifice of the orbit.

PMID- 16297697
TI  - The effect of chitosan bead encapsulating calcium sulfate as an injectable bone
      substitute on consolidation in the mandibular distraction osteogenesis of a dog
      model.
AB  - PURPOSE: The purpose of this project was to study the effect of chitosan bead
      encapsulating calcium sulfate, which provides a sustained release of chitosan and
      calcium sulfate after implantation, on early bony consolidation in distraction
      osteogenesis of a dog model. MATERIALS AND METHODS: Forty-five dogs were used for
      this study. An external distraction device was applied to the mandibular body
      after a vertical osteotomy and mandibular distraction was initiated 5 days after
      the operation at a rate of 1 mm/day up to a 10-mm distraction. The experimental
      group was divided into a control group (I), hyaluronic acid group (II), chitosan
      group (III), calcium sulfate group (IV), and chitosan bead encapsulating calcium
      sulfate group (V). Normal saline was injected in group I. In group II, 1 mL of
      hyaluronic acid solution was injected into the distracted region. In group III, 1
      mL of injectable solution of chitosan mixed with hyaluronic acid was implanted.
      In group IV, 1 mL of injectable solution of calcium sulfate mixed with hyaluronic
      acid was implanted. In group V, an injectable form of powdered chitosan bead
      encapsulating calcium sulfate mixed with 1 mL volume of hyaluronic acid was
      implanted. RESULTS: Bone mineral density was 12% of the contralateral normal
      mandible at 3 weeks, 23.4% at 6 weeks in group I, 15% at 3 weeks, 29.1% at 6
      weeks in group II, 16% at 3 weeks and 32% at 6 weeks in group III, 30.4% at 3
      weeks and 52.8% at 6 weeks in group IV, and 33.6% at 3 weeks and 55% at 6 weeks
      in group V with statistical significance (P < .005). The mean 3-point failure
      load was compared with the intact contralateral mandible and noted to be 12% in
      the control group, 16% in group II, 18% in group III, 34.3% in group IV, and
      31.7% in group V. Difference of mean percentages between one group and another
      was statistically significant (P < .005). In the histologic findings, new bone
      was generated in all groups. In groups IV and V, the formation of active woven
      bone was observed throughout the distracted region at 6 weeks. The amount of new
      bone formation in the distracted zone was in the order of group IV and V, III and
      II, and the control group. CONCLUSIONS: These findings suggest that chitosan bead
      encapsulating calcium sulfate appears to facilitate early bony consolidation in
      distraction osteogenesis.

PMID- 16297699
TI  - Reconstruction of maxillary defects: the case for prosthetic rehabilitation.

PMID- 16297700
TI  - Brown recluse spider bite to the face.

PMID- 16297701
TI  - Temporomandibular joint ankylosis after condylar fracture with penetration of the
      condyle in the medium cranial fossa.

PMID- 16297703
TI  - Frequency of trigeminal nerve injuries following third molar removal.

PMID- 16297704
TI  - Cutaneous melanoma susceptibility and progression genes.
AB  - This review aims to provide an up-to-date view on our understanding of the
      molecular genetics of melanoma development. It gives an overview of genes (and
      loci) currently known to be substantially involved in melanoma predisposition and
      progression. Broadly, the review falls into 3 sections: genes/loci involved in
      melanoma susceptibility through germline mutation, tumor suppressor genes
      somatically mutated or deleted in melanoma, and oncogenes mutated somatically in
      melanoma. The main cellular pathways in which these genes are involved are
      summarized and discussed. From this it is evident that abberations of cell cycle
      regulation, DNA repair and receptor-mediated signal transduction are important
      for melanocytic neoplasia.

PMID- 16297705
TI  - Autoantibodies in breast cancer sera: candidate biomarkers and reporters of
      tumorigenesis.
AB  - A plethora of promising breast cancer-associated autoantigens have been cloned by
      immunoscreening cDNA expression libraries with breast cancer sera or identified
      using proteomics, yet no biomarkers, whether individual autoantigens or panels of
      antigens developed using antibody-based methods have been validated and
      incorporated to routine oncologic practice for the early diagnosis of breast
      cancer. Recently, the addition of genomics, proteomics and high throughput
      technology to traditional immunological techniques has revived the interest in
      this field, and some of the most promising breast cancer autoantigens are in the
      process of being validated prospectively in large cohorts of patients with breast
      cancer. In addition, some of the identified breast cancer-associated autoantigens
      are recognized by T-cells and may prove to have a role in the treatment of breast
      cancer in the future. Autoantibodies found in breast cancer patient sera provide
      important clues about their significance. The discovery of breast cancer
      associated antigens has provocative implications beyond the quest for novel
      diagnostic biomarkers, because autoantibodies target molecules involved in signal
      transduction, cell cycle regulation, cell proliferation and apoptosis, all of
      them key processes in carcinogenesis. Molecular components of the DNA double
      strand break repair machinery as well as several members of the rapamycin
      sensitive pathway elicit an autoantibody response in breast cancer. Data obtained
      by screening cDNA expression libraries of breast cancer antigens with
      autoantibodies present in breast cancer sera suggest that autoantibodies in
      cancer sera may be linked to the process of apoptosis. The studies reviewed here,
      clearly demonstrate the participation of autoimmunity in breast cancer to an
      extent previously unsuspected, which may have broad implications for the
      discovery of molecular targets for drug therapy and cancer biomarkers in general.

PMID- 16297706
TI  - Frequent c-Kit gene mutations not only in gastrointestinal stromal tumors but
      also in interstitial cells of Cajal in surrounding normal mucosa.
AB  - Gastrointestinal stromal tumors (GISTs) are thought to originate from mesenchymal
      stem cells that differentiate toward the interstitial cells of Cajal (ICCs). The
      frequent occurrence of activating mutations involving exon 11 of c-Kit gene in
      sporadic GISTs indicates an important role in genesis of this tumor type. In the
      present study we examined c-Kit gene mutations in a series of GISTs and also in
      ICCs of surrounding normal tissues. Samples from 18 patients were monitored
      immunohistochemically for c-Kit expression and microdissected for sequencing
      analysis of exons 9, 11, 13, and 17 of the c-Kit gene. It was revealed to be
      mutated in exon 11 or adjacent introns in 9 out of the total of 18 (50.0%) GISTs.
      In 6 (33.3%) cases, mutations in ICCs were also detected in the same exon. With
      stomach GISTs, 8 of 16 (50.0%) cases harbored mutations and 4 had mutations in
      background ICCs (25.0%). In contrast counterpart ICCs in gastric cancer cases
      harbored no c-Kit gene mutations (0 out of 24=0%) (P<0.02). ICCs undergoing c-Kit
      mutation as a possible early initiation step in GIST tumorigenesis may thus have
      pre-neoplastic potential.

PMID- 16297707
TI  - S100A4 regulates E-cadherin expression in oral squamous cell carcinoma.
AB  - S100A4 has multiple functions in cell cycle progression and cell motility, and
      has been implicated in cancer invasion. In this study, we examined the expression
      of S100A4, E-cadherin and its related proteins in oral squamous cell carcinoma
      (SCC) cell lines with different invasive phenotypes, grade 4C and 4D.
      Furthermore, grade 4C OSC-19 cells expressing E-cadherin were transfected with
      S100A4-expression vector and the expression of E-cadherin-related proteins in the
      stable clone was examined to elucidate the relationship between S100A4 and E
      cadherin. Constitutive over-expression of S100A4 in stable transformant of OSC-19
      (OSC-19/S100A4) cells led to down-regulation of E-cadherin and beta-catenin.
      Furthermore, grade 4D invasive cell lines (HOC313 and TSU) expressing S100A4 mRNA
      did not express E-cadherin, P-cadherin, and beta-catenin, while gamma-catenin
      protein was only weakly expressed. Thus, the mRNA expression of E-cadherin was
      reversely correlated with S100A4 expression in oral SCCs. Interestingly, vascular
      endothelial growth factor-C was up-regulated in OSC-19/S100A4 cells. In summary,
      S100A4-mediated regulation of E-cadherin expression may play an important
      mechanism in invasion and metastasis of oral SCC.

PMID- 16297708
TI  - Soybean saponins suppress the release of proinflammatory mediators by LPS
      stimulated peritoneal macrophages.
AB  - Proinflammatory mediators such as prostaglandins (PGs), nitric oxide (NO),
      certain inflammatory cytokines and chemokines play a pivotal role in tumor
      development. The anti-inflammatory properties of naturally occurring
      phytochemicals are associated with significant reduction in the risk of certain
      cancers in vitro and in vivo. In the present study, we investigated the effects
      of soybean saponins on the production of proinflammatory mediators in LPS
      stimulated peritoneal macrophages. Soybean saponins significantly inhibited the
      release of PGE(2), NO, TNFalpha and monocyte chemotactic protein-1 (MCP-1) in a
      dose-dependent manner. Soybean saponins also down-regulated the expression of COX
      2 and iNOS at mRNA/protein levels. Moreover, soybean saponins suppressed NF
      kappaB activation by blocking IkappaB-alpha degradation. Our data indicate that
      soybean saponins exhibit anti-inflammatory properties by suppressing the
      transcription of inflammatory cytokine genes through the NF-kappaB signaling
      pathway. The anti-inflammatory properties of soybean saponins may be useful for
      ameliorating inflammatory diseases as well as suppressing tumor progression.

PMID- 16297709
TI  - Caspase-3-dependent protein kinase C delta activity is required for the
      progression of Ginsenoside-Rh2-induced apoptosis in SK-HEP-1 cells.
AB  - Ginsenoside-Rh2 (G-Rh2) has been shown to induce apoptosis in a variety of cell
      types. In this study, we show that G-Rh2-induced apoptosis is accompanied by the
      mitochondrial release of cytochrome c and activation of caspase-3 in the human
      hepatoma cell line, SK-HEP-1. Furthermore, protein kinase C delta (PKCdelta)
      activity was markedly up-regulated in a lipid activator-independent manner with
      kinetics similar to those of PKCdelta and PARP cleavages during the apoptotic
      progression. Pre-treatment of cells with the caspase-3 specific inhibitor (z-DEVD
      fmk) effectively prevented the G-Rh2-induced proteolytic activation of PKCdelta.
      Moreover, rottlerin, a specific PKCdelta inhibitor blocked G-Rh2-induced
      proapoptotic effects on the cells including the release of cytochrome c,
      activation of caspase-3 activity, and proteolytic cleavage and activation of
      PKCdelta. These results suggest that G-Rh2-induced apoptosis is functionally
      linked to mitochondrial dysfunction and caspase-3 activity is regulated by
      positive feedback with PKCdelta via the mitochondrial pathway.

PMID- 16297710
TI  - Chemopreventive properties of the ethanol extract of chinese licorice
      (Glycyrrhiza uralensis) root: induction of apoptosis and G1 cell cycle arrest in
      MCF-7 human breast cancer cells.
AB  - Much of the interest on the chemopreventive properties of licorice has been
      focused on the plant genius Glycyrrhiza glabra. In this study the ethanol extract
      of Chinese licorice root, Glycyrrhiza uralensis (G. uralensis) was investigated
      for its estrogenic effect and the ability to inhibit cell proliferation in the
      MCF-7 human breast cancer cell line. The extract of the root of G. uralensis was
      fractionated in EtOH:H(2)O (80:20) (80% ethanol). The extract exhibited
      estrogenic effects similar to 17beta- estradiol (E2) and induced apoptosis at the
      same dose level (100 microg/ml) in MCF-7 breast cancer cells, results were
      associated with up-regulation of tumor suppressor gene p53 and pro-apoptotic
      protein Bax. G. uralensis extract caused the up-regulation of p21(waf1/cip1) and
      down-regulation of cdk 2 and cyclin E and most significantly, induced G1 cell
      cycle arrest. This is the first study to show that the ethanolic extract of the
      root of G. uralensis has an estrogen-like activity and anti-cancer effects
      against MCF-7 human breast cancer cells. Whilst the use of phytoestrogens to
      protect against hormone-dependent cancers or as a 'natural' alternative to
      hormone replacement therapy remains controversial, the data in this paper support
      the suggestion that extracts of root of the Chinese licorice G. uralensis might
      be of importance in this debate.

PMID- 16297711
TI  - Involvement of Bcl-2 family, cytochrome c and caspase 3 in induction of apoptosis
      by beauvericin in human non-small cell lung cancer cells.
AB  - Beauvericin (BEA), a cyclic hexadepsipeptide from Codyceps cicadae, possesses
      anti-convulsion, anti-arrhythmia, sedation, and anti-tumor activities. It has
      been reported that BEA induces apoptosis in several cancer cell lines. However,
      the molecular mechanism underlying the BEA-induced apoptotic process is not yet
      clearly understood. In the present study, the intracellular signaling pathways of
      BEA-induced apoptosis in human non-small cell lung cancer (NSCLC) A549 cells were
      investigated using morphological analysis and terminal deoxynucleotidyl
      transferase dUTP nick-end labeling (TUNEL) technique. In this study, BEA-induced
      apoptosis in human NSCLC A549 cells demonstrated a BEA concentration- and
      treatment time-dependent manner. This BEA-induced apoptosis in human NSCLC A549
      cells was also accompanied by the up-regulation of Bax, Bak, and p-Bad and down
      regulation of p-Bcl-2, but no effect on the levels of Bcl-X(L) or Bad proteins.
      Moreover, the BEA treatment resulted in a significant reduction of mitochondrial
      membrane potential, increase in the release of mitochondrial cytochrome c (cyt
      c), and activation of caspase 3. Furthermore, treatment with caspase 3 inhibitor
      (z-DEVD-fmk) was capable to prevent the BEA-induced caspase 3 activity and cell
      death. These results clearly demonstrate that the induction of apoptosis by BEA
      involves multiple cellular/molecular pathways and strongly suggest that pro- and
      anti-apoptotic Bcl-2 family proteins, mitochondrial membrane potential,
      mitochondrial cyt c, and caspase 3, they all participate in BEA-induced apoptotic
      process in human NSCLC A549 cells.

PMID- 16297712
TI  - DNA damage and G2/M arrest in Syrian hamster embryo cells during Malachite green
      exposure are associated with elevated phosphorylation of ERK1 and JNK1.
AB  - Malachite Green (MG), consisting of green crystals with a metallic luster, is
      highly soluble in water, cytotoxic to various mammalian cells and also acts as a
      liver tumor promoter. In view of its industrial importance and possible exposure
      to human beings, MG poses a potential environmental health hazard. We have
      earlier reported the malignant transformation of Syrian hamster embryo (SHE)
      cells in primary culture by MG. In this study, we have studied the ability of MG
      to cause DNA damage, cell cycle arrest, apoptosis and possible roles of ERK, JNK
      and p38 MAP kinases. Exposure of SHE cells to MG causes DNA damage. Flow
      cytometric analysis showed an increase of G2/M phase and apoptotic cells in MG
      treated cells compared to control SHE cells. Western blots of MG treated cells
      with phosphoactive antibodies showed elevated phosphorylation of ERK1 and JNK1
      and no change in p38 kinase. However, total forms of ERKs, JNKs and p38 kinases
      showed similar levels of expression in control and MG treated SHE cells. The
      present study indicates that elevated phosphorylation of ERK1 and JNK1 and an
      increase in G2/M phase and apoptotic cells seems to be the changes associated
      with MG exposure to SHE cells in primary culture.

PMID- 16297713
TI  - 5-Aza-2'-deoxycytidine induces retinoic acid receptor-beta(2) demethylation and
      growth inhibition in esophageal squamous carcinoma cells.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most common tumors in
      human. Previous studies showed that multiple genetic and epigenetic alterations
      involved in carcinogenesis of esophagus, whereas the molecular mechanisms are
      poorly understood. So far, more and more ESCC-related genes have been found and
      retinoic acid receptor beta(2) (RARbeta(2)) is such a gene which was recognized
      as a putative tumor suppressor gene since reduced RARbeta(2) mRNA expression has
      been observed in several solid tumors, including ESCC. A growing evidence
      indicated that RARbeta(2) was required for the growth inhibitory effect of
      retinoic acid (RA). However, the molecular mechanism of its inactivation remained
      obscure in ESCC. The RARbeta2 methylation status was assessed by methylation
      specific PCR (MSP) in 12 ESCC cell lines and compared with their mRNA and protein
      expression level. Bisulfite sequencing of RARbeta(2) promoter region was
      performed to confirm the MSP results. After 5-aza-2'-deoxycytidine (5-aza-dc)
      treatment the expression of RARbeta(2) was reversed in two RARbeta(2)
      downregulated cell lines. Therefore, hypermethylation of the promoter regions of
      RARbeta2 gene is a major mechanism of transcriptional inactivation and might be
      involved in tumor development of esophagus in some ESCC cell lines suggesting
      that multiple mechanisms contribute to the loss of RARbeta(2) expression in ESCC
      cell lines. Furthermore, the methylation status of RARbeta(2) promoter region and
      its expression was analyzed in 51 ESCC tissue samples with their adjacent normal
      epithelia and two normal esophageal epithelia. The results showed that there was
      a statistically significant correlation between methylation status of RARbeta(2)
      and tumor grade; Moreover, a relationship between methylation status and
      decreased RARbeta(2) expression was found only in G(2) stage tumors. After 5-aza
      dc treatment, RARbeta(2) restoration was accompanied by growth inhibition and
      this might be one of the mechanisms but not the only mechanism for the tumor cell
      growth inhibition by 5-aza-dc. This study may have clinical applications for ESCC
      therapy and prevention.

PMID- 16297714
TI  - Cytogenetic effects in children treated with methylphenidate.
AB  - In recent years there has been a surge in methylphenidate (Ritalin) use for
      treatment of attention deficit/hyperactivity disorder (ADHD) in children.
      However, there is a paucity of information on whether this drug poses any
      potential health risks, such as mutagenicity or carcinogenicity, for humans. To
      address this issue, we investigated whether this central nervous system stimulant
      produces cytogenetic abnormalities in pediatric patients at therapeutic levels.
      In a population composed of twelve children treated with therapeutic doses of
      methylphenidate, we analyzed three cytogenetic endpoints in peripheral blood
      lymphocytes obtained before and three months after initiation of treatment with
      this drug. In all participants, treatment induced a significant 3, 4.3 and 2.4
      fold increase in chromosome aberrations, sister chromatid exchanges and
      micronuclei frequencies, respectively (P=0.000 in all cases). These findings
      warrant further investigations of the possible health effects of methylphenidate
      in humans, especially in view of the well-documented relationship between
      elevated frequencies of chromosome aberrations and increased cancer risk.

PMID- 16297715
TI  - Comment on "Interleukin-1 beta gene promoter variants are associated with an
      increased risk of gastric cancer in a Chinese population" by Yang et al.

PMID- 16297716
TI  - Nasopharyngeal carcinoma with cranial nerve palsy: the importance of MRI for
      radiotherapy.
AB  - PURPOSE: To evaluate various prognostic factors and the impact of imaging
      modalities on tumor control in patients with nasopharyngeal cancer (NPC) with
      cranial nerve (CN) palsy. MATERIAL AND METHODS: Between September 1979 and
      December 2000, 330 NPC patients with CN palsy received radical radiotherapy (RT)
      by the conventional opposing technique at Chang Gung Memorial Hospital-Linkou.
      Imaging methods used varied over that period, and included conventional
      tomography (Tm) for 47 patients, computerized tomography (CT) for 195 patients,
      and magnetic resonance image (MRI) for 88 patients. Upper CN (II-VI) palsy was
      found in 268 patients, lower CN (IX-XII) in 13, and 49 patients had both. The
      most commonly involved CN were V or VI or both (23%, 12%, and 16%, respectively).
      All patients had good performance status (World Health Organization <2). The
      median external RT dose was 70.2 Gy (range, 63-77.5 Gy). Brachytherapy was also
      given to 156 patients in addition to external RT, delivered by the remote after
      loading, high-dose-rate technique. A total of 139 patients received cisplatin
      based chemotherapy, in 115 received as neoadjuvant or adjuvant chemotherapy and
      in 24 concomitant with RT. Recovery from CN palsy occurred in 171 patients during
      or after radiotherapy. Patients who died without a specific cause identified were
      regarded as having died with persistent disease. RESULTS: The 3-year, 5-year, and
      10-year overall survival was 47.1%, 34.4%, and 22.2%. The 3-year, 5-year, and 10
      year disease-specific survival (DSS) rates were 50.4%, 37.8%, and 25.9%. The 5
      year DSS for patients staged with MRI, CT, and Tm were 46.9%, 36.7%, and 21.9%,
      respectively (p = 0.016). The difference between MRI and CT was significant (p =
      0.015). The 3-year and 5-year local control rates were 62% and 53%, respectively.
      The 5-year local control was 68.2% if excluding patients who died without a
      specific cause. Patients who had an MRI had a significantly better tumor control
      rate than those evaluated with CT or Tm, with a 15-30% improvement in local tumor
      control and survival. Patients with extensive CN palsy had worse survival than
      those with only lower CN or upper CN involvement (5-year DSS 20.4% vs. 43.2% and
      40.4%, respectively; p < 0.001). Patients who recovered from CN palsy had better
      survival than those who did not (47% vs. 26%, p < 0.001). Brachytherapy was
      associated with poorer local control, whereas a total external dose of more than
      70 Gy improved local tumor control and marginally improved DSS. Subgroup analysis
      in CT and MRI patients group, either DSS or OS was significantly associated with
      imaging modality, N stage, or location of or remission of CN palsy. CONCLUSION:
      The use of MRI was associated with improved tumor control and survival of
      patients with NPC causing CN palsy. Patients recovering from CN palsy had better
      survival. A higher radiation dose delivered by external beam may achieve better
      tumor control than brachytherapy.

PMID- 16297717
TI  - Radioprotective effect of amifostine on parotid gland functioning is region
      dependent.
AB  - PURPOSE: To investigation the protective ability of amifostine during partial
      irradiation of the rat parotid gland. METHODS AND MATERIALS: Single-dose X-ray
      irradiation was performed by use of collimators with conformal radiation portals
      for either the 100% volume (15 Gy) or the 50% cranial/caudal partial parotid
      gland volumes (30 Gy). Amifostine was administered intraperitoneally at a dose of
      250 mg per kg body weight, 25 minutes before irradiation. Saliva flow rates,
      gland weights, and the tissues of the individual lobes were investigated up to 1
      year after treatment. RESULTS: A clear protective effect of amifostine was found
      against loss of saliva flow, the altered appearance of gross morphology, loss of
      gland weight, and histopathologic changes for the 100% volume gland irradiations
      and for the 50% volume cranial irradiations but not for the 50% volume caudal
      irradiations. CONCLUSIONS: The protective ability of amifostine is strongly
      dependent on the irradiated glandular region and observed for later damage only.
      The major effect of the drug seems to be the prevention of volume effects caused
      by secondary damage that occurs in shielded parts of the gland. The results of
      the present study show that understanding of the anatomy and physiology of organs
      that are to be spared is necessary to ensure optimal preservation of function.

PMID- 16297718
TI  - The need for rotational margins in intensity-modulated radiotherapy and a new
      method for planning target volume design.
AB  - PURPOSE: The effect of rotational errors on the coverage of clinical target
      volumes (CTVs) is examined. A new planning target volume (PTV) construction that
      considers the individual paths traced by movements of the target boundary points
      is developed. METHODS AND MATERIALS: A standard uniform margin expansion was
      compared with a PTV constructed from the space swept out by a concave moving
      target. A new method formed the PTV by aggregating the separate convex hulls
      taken of the positions of the individual target boundary points in a sampling of
      CTV displacements. RESULTS: A 0.5-cm uniform margin adequate for translations was
      inadequate given CTV rotation about a fixed off-center axis. A PTV formed of the
      target's swept-out area was 22% smaller than needed for coverage by a uniform
      margin, but computationally is not readily extended to translations combined with
      rotations about a shifting axis. Forming instead the union of convex hulls of the
      boundary points in a sampling of CTV displacements represented these movements in
      the PTV design and retained the target's concave shape. CONCLUSIONS: Planning
      target volumes should accommodate target rotation. The union of convex hulls of
      the boundary point positions in a sampling of displacements can effectively
      represent multiple sources of deviations while preserving target concavities.

PMID- 16297720
TI  - Systemic therapies for joint disease in horses.
AB  - Systemic therapies for joint disease may be prescribed when a single joint is
      involved or when multiple sites are affected. The precise therapeutic regimen
      recommended depends on the duration,cause, and site(s) of injury and is often an
      adjunct to intra-articular or supportive therapies. If the clinical signs of
      joint disease are acute and moderate in severity, nonsteroidal anti-inflammatory
      drugs are often administered to alleviate pain and inflammation. When aiming for
      more of a generalized maintenance or chondro-protective regimen, an alternative
      medication, such as hyaluronan,polysulfated glycosaminoglycan, or a nutraceutical
      will commonly be prescribed.

PMID- 16297721
TI  - Intra-articular injections for joint disease in horses.
AB  - Lameness remains an important source of reduced performance in many types of
      horses. Pain referable to joints is among the most common causes, and intra
      articular injections remain a common and important means of addressing lameness
      referable to joints in horses.

PMID- 16297722
TI  - The use of nutraceuticals for osteoarthritis in horses.
AB  - In horses, lameness is often attributable to some degree of osteoarthritis (OA),
      a complex disease process that is highlighted by eventual degradation of
      articular cartilage. Conventional therapies for OA in horses are designed to
      relieve pain and discomfort and often include pharmacologic intervention with
      nonsteroidal anti-inflammatory drugs or intra-articular steroids. Oral
      administration of nutraceutical products to the horse is common and easy and is
      perceived to be a benign treatment for OA in horses. The main goal for use of
      nutraceuticals is to use them in OA cases to attempt to lower the dose of other
      drugs that are more problematic while potentially preventing further degradation
      (disease or structure modifying). This article attempts to define a
      nutraceutical, identifies areas that need to be considered when these products
      are used, and describes the known scientific effects of the most common compounds
      contained in currently available equine nutraceuticals.

PMID- 16297723
TI  - Equine rehabilitation therapy for joint disease.
AB  - The principles of physical rehabilitation therapy can be applied to the horse to
      provide a reduction in discomfort and dysfunction associated with the various
      forms of joint disease. Physical agents,such as ice, heat, electricity, sound,
      light, magnetic fields, compression, and movement, can be used by the
      rehabilitation therapist to attempt to control pain, reduce swelling, and restore
      optimal movement and function in the affected joint. The equine therapist's
      attention is focused not only on the affected joint but on the body as a whole to
      manage secondary or compensatory problems.

PMID- 16297724
TI  - Extracorporeal shock wave therapy for treatment of osteoarthritis in the horse:
      clinical applications.
AB  - Veterinarians have begun using extracorporeal shock wave therapy (ESWT) for
      treatment of osteoarthritis (OA) in horses, although relatively little
      information has been published about its efficacy or mechanism of action. As a
      clinician, it can be difficult to know if and when ESWT should be recommended.
      Case studies in which ESWT is used to treat advanced OA in horses are discussed.
      ESWTseems to be a valuable adjunct for management of equine OA. It is the purpose
      of this article to discuss indications and techniques as well as to share
      clinical experiences using ESWT in the treatment of OA in the horse.

PMID- 16297725
TI  - Diagnosis and treatment of septic arthritis.
AB  - Septic arthritis (SA) is a common orthopedic condition encountered in horses that
      are presented to equine veterinarians. Successful out-come is dependent on prompt
      and thorough evaluation and treatment. This article briefly reviews the
      pathophysiology, outlines diagnostics, describes treatment options and
      prognostics, and discusses current research in diagnosis and treatment of SA.

PMID- 16297726
TI  - Diagnosis and treatment of ligamentous and meniscal injuries in the equine
      stifle.
AB  - The accuracy of the diagnosis of ligamentous and meniscal injuries in the equine
      stifle has improved significantly in the last 20 years. There are, however,
      significant limitations in the diagnosis of stifle injuries because of the size
      and anatomy of the equine stifle. Treatment of soft tissue injuries to the equine
      stifle has been empirical,with only a few large case studies for specific
      conditions of stifle ligaments and menisci and only retrospective case studies of
      the outcome of treatment. This article describes the diagnosis and treatment of
      ligamentous and meniscal injuries in the equine stifle using information from the
      author's own experience and from reports in the scientific literature.

PMID- 16297727
TI  - New surgical treatments for osteochondritis dissecans and subchondral bone cysts.
AB  - Osteochondritis dissecans (OCD) and subchondral bone cysts (SBCs) occur commonly
      and at many different locations in equine limbs and can lead to secondary
      osteoarthritis when left untreated. Depending on the location and extent of the
      lesion, arthroscopic surgical debridement may be an effective treatment for
      returning a horse to athletic soundness. In many cases, however, additional
      techniques to improve the healing response in bone and cartilage are needed so as
      to preserve articular function. Methods for improving cartilage repair (ie,
      restoration of damaged cartilage)or regeneration (ie, reformation or recreation
      of new articular cartilage) in select cases of OCD and SBCs are discussed.

PMID- 16297728
TI  - Arthrodesis techniques in horses.
AB  - When medical therapy and surgical treatments of an injured joint fail to return
      the animal to athletic performance or comfortable use of the limb, arthrodes is
      is a final option for some joints. Arthrodesis refers to the surgical fusion of a
      joint, resulting in bony ankylosis. Successful arthrodesis requires debridement
      of the articular cartilage through the calcified cartilage layer, exposing the
      subchondral bone; alignment of the joint into a weight-bearing position; and
      stabilization. The methods by which these steps are accomplished are variable,
      depending on the individual joint. There are currently accepted methods for
      arthrodesis of several joints in the horse; however, not all joints are amenable
      to arthrodesis. Case selection is an important aspect of performing arthrodesis
      procedures in horses.

PMID- 16297729
TI  - Future directions in treatment of joint disease in horses.
AB  - Osteoarthritis is one of the most economically important diseases facing equine
      practitioners. The loss of use associated with joint disease is a leading problem
      in the equine industry. Although osteoarthritis in all species is believed to be
      a multifactorial disease that is not well understood, significant advances are
      being made. This article presents areas of research that are relatively well
      developed but have not made it to commercialization or routine clinical practice
      and looks at new applications being investigated for peo-ple that may have an
      equine application.

PMID- 16297731
TI  - Adult osteomyelitis.
AB  - Adult osteomyelitis remains difficult to treat, with considerable morbidity and
      costs to the health care system. Bacteria reach bone through the bloodstream,
      from a contiguous focus of infection, from penetrating trauma, or from operative
      intervention. Bone necrosis begins early, limiting the possibility of eradicating
      the pathogens, and leading to a chronic condition. Appropriate treatment includes
      culture-directed antibiotic therapy and operative debridement of all necrotic
      bone and soft tissue. Treatment often involves a combination of antibiotics.
      Operative treatment is often staged and includes debridement, dead space
      management, soft tissue coverage, restoration of blood supply, and stabilization.
      Clinicians and patients must share a clear understanding of the goals of
      treatment and the difficulties that may persist after the initial course of
      therapy or surgical intervention. Chronic pain and recurrence of infection still
      remain possible even when the acute symptoms of adult osteomyelitis have
      resolved.

PMID- 16297732
TI  - Osteomyelitis in children.
AB  - Osteomyelitis is one of the more common invasive bacterial infections in children
      leading to hospitalization and prolonged antibiotic administration. Over the past
      decade, increasing microbial virulence, diminishing antibiotic susceptibility,
      and advances in diagnostic molecular microbiology and imaging techniques have led
      to changes in the clinical management of children with suspected osteomyelitis,
      which are reviewed in this article.

PMID- 16297733
TI  - Septic arthritis.
AB  - Septic arthritis has increased in incidence in the United States in the past two
      decades, and increasingly affects an older population with a greater burden of
      chronic illness and a higher risk for drug-resistant organisms. Successful
      management depends on a high diagnostic suspicion, empiric antibiotic treatment,
      and joint drainage. A bacteriologic diagnosis is more likely with inoculation
      into blood culture bottles than plating on solid media. As MRSA increases in
      prevalence in the community, empiric anti-biotic regimens increasingly need to be
      active against MRSA.

PMID- 16297734
TI  - Mycobacterial osteomyelitis and arthritis.
AB  - Physicians can expect to see more mycobacterial bone and joint disease in North
      America as a result of increased travel, immigration, and use of
      immunosuppressive medications. The first step in treating infections caused by
      these organisms is to consider the diagnosis early in the course of illness. Long
      standing untreated mycobacterial infections typically cause significant bone
      destruction and loss of function. The treatment of mycobacterial bone and joint
      infection requires prolonged antibiotic therapy, often in conjunction with
      surgical intervention, particularly for spinal tuberculosis.

PMID- 16297735
TI  - Fungal arthritis and osteomyelitis.
AB  - Fungal arthritis and osteomyelitis are uncommon diseases and generally present in
      an indolent fashion. The incidence of fungal bone and joint dis-ease is
      increasing with an increase in the prevalence of factors predisposing to invasive
      fungal disease, such as the use of central venous catheters, broad spectrum
      antibiotics, immunosuppression, and abdominal surgery. Definitive diagnosis
      relies on bone or synovial culture or biopsy. Successful management has
      traditionally consisted of amphotericin B in combination with surgical
      debridement. Given the rarity of this disease, treatment is not well defined, but
      reports of success with the use of azole antifungal agents, including
      itraconazole, fluconazole, voriconazole, and posaconazole, are promising.

PMID- 16297736
TI  - Gonococcal arthritis (disseminated gonococcal infection).
AB  - Septic arthritis caused by N gonorrhoeae is monoarticular or pauciarticular, and
      is more commonly associated with positive synovial fluid cultures and negative
      blood cultures. Gonococcal bacteremia is more likely to be associated with
      polyarthralgias and skin lesions. The diagnosis of gonococcal arthritis or DGI is
      also secure if a mucosal gonococcal infection is documented in the presence of a
      typical clinical syndrome that responds promptly to appropriate antimicrobial
      therapy. Hospitalization is indicated in patients with suppurative arthritis or
      when the diagnosis is in doubt. Initial treatment with ceftriaxone or another
      advanced-generation cephalosporin is warranted until signs and symptoms have
      improved; continuation of treatment for a total period of therapy of 1 week can
      be accomplished with a fluoroquinolone.

PMID- 16297737
TI  - Reactive arthritis.
AB  - ReA consists of sterile axial or peripheral articular inflammation,enthesitis,
      and extra-articular manifestations. Most patients are HLA-B27 positive, although
      determining the B27 status of an individual patient is irrelevant. Exposure to
      specific bacterial antigens is usually the inciting factor. Diagnosis usually can
      be made by clinical examination and history. The current standard therapy is
      NSAIDs and physiotherapy, but molecular biologic treatment may ultimately become
      the mainstay in recalcitrant and severe ReA.

PMID- 16297738
TI  - Prosthetic joint infections.
AB  - Success in the treatment of infected orthopedic prosthesis requires the best
      surgical approach in combination with prolonged optimum targeted antimicrobial
      therapy. In choosing the surgical option, one must consider the type of
      infection, condition of the bone stock and soft tissue, the virulence and
      antimicrobial susceptibility of the pathogen, the general health and projected
      longevity of the patient, and the experience of the surgeon. If surgery is not
      possible, an alternative is long-term oral antimicrobial suppression to maintain
      a functioning prosthesis. Treatment must be individualized for a specific
      infection in a specific patient.

PMID- 16297739
TI  - Management of open fractures.
AB  - Open fractures are high-energy injuries that require a principle-based approach,
      starting with detailed evaluation of patient status and injury severity. Early,
      systemic, wide-spectrum antibiotic therapy should cover gram-positive and gram
      negative organisms, and a common regimen is a 3-day administration of a first
      generation cephalosporin and an aminoglycoside, supplemented with ampicillin or
      penicillin to cover anaerobes in farm or vascular injuries. Local antibiotic
      delivery with the bead pouch technique increases the local concentration of
      antibiotics, minimizes systemic toxicity, and prevents secondary wound
      contamination. Thorough irrigation and surgical debridement is critical for
      prevention of infection. Primary wound closure remains controversial because of
      concerns for gas gangrene. Partial wound closure is an alternative, with delayed
      wound closure within 3 to 7 days. In the presence of extensive soft tissue
      damage, local or free muscle flaps should be transferred to achieve coverage.
      Stable fracture fixation should be achieved with a method suitable for the bone
      and soft tissue characteristics. Early bone grafting is indicated for bone
      defects, unstable fractures treated with external fixation, and delayed union. A
      management plan guided by the above principles will achieve the goals of
      prevention of infection, fracture healing, and restoration of function in most of
      these challenging injuries.

PMID- 16297740
TI  - Antibiotic prophylaxis in orthopedic prosthetic surgery.
AB  - The problem of prophylaxis in orthopedic implant surgery will become increasingly
      important and complex as the population ages and requires more arthroplasty
      procedures, and the prevalence of antimicrobial-resistant bacteria meanwhile also
      continues to rise. Energy spent preventing prosthetic joint infection is more
      effective than that expended in treating the infection of a prosthetic joint,
      once established. Preventive measures encompass a wide array of variables related
      to host response, wound environment, and microorganisms. Prophylaxis should
      address these areas in the preoperative, intraoperative, and postoperative
      periods. Antimicrobial prophylaxis remains the single most effective method of
      reducing the prevalence of infection after total joint arthroplasty. In the
      postoperative period, prophylaxis aims to protect the prosthetic joint against
      hematogenous seeding from oral, urologic, skin, or gastrointestinal sources.
      Currently, dental and urologic advisory statements provide recommendations for
      antimicrobial prophylaxis for high-risk patients with total joint arthroplasty
      undergoing high-risk procedures. Close collaboration between the orthopedic
      surgeon, urologist, or dentist and the infectious disease specialist is crucial
      for providing recommendations regarding prophylaxis in special circumstances. In
      these particular circumstances, individual decisions should be made based on
      clinical judgment.

PMID- 16297741
TI  - Lyme arthritis.
AB  - Lyme borreliosis continues to be a significant public health problem. Because of
      good public education, the incidence of Lyme arthritis and other late-stage
      symptoms has not increased in tandem with the increases in early infection. There
      have been major advances in the understanding of the pathogenesis of Lyme
      arthritis. The understanding of mechanisms of arthritis in Lyme borreliosis may
      also shed light on the mechanisms of disease in other infectious and
      noninfectious arthritides.

PMID- 16297742
TI  - Viral arthritis.
AB  - The role of viruses in the development of acute and chronic arthritis is complex,
      because viruses are ubiquitous, and all human beings are occasionally afflicted
      by viral infections. In general, most viral infections are acute and self
      limiting and survive by infecting one susceptible host, then moving on to
      another. Some viruses establish prolonged latency in the host after acute
      infection, whereas other agents produce chronic infections following the primary
      stage. The mechanisms whereby these infections produce arthritis are diverse and
      still poorly understood, but are clearly influenced by both host and viral
      factors. This review addresses these and other common forms of viral arthritis,
      such as that caused by parvovirus B19.

PMID- 16297743
TI  - Tropical and temperate pyomyositis.
AB  - Pyomyositis is a primary infection of skeletal muscle not arising from contiguous
      infection, presumably hematogenous in origin, and often, but not invariably,
      associated with abscess formation. Classically, pyomyositis is an infection of
      the tropics, occurring in previously active and healthy young men. Pyomyositis in
      temperate countries is often regarded as an infection that occurs in hosts who
      are immunocompromised or otherwise debilitated. However,this distinction may be
      somewhat artificial, as tropical pyomyositis may be partly related to underlying
      infection with HIV or parasites, and temperate pyomyositis has been reported in
      healthy and athletic persons. This article discusses the pathogenesis, clinical
      presentation, diagnosis, and management of pyomyositis in the tropical and
      temperate settings.

PMID- 16297744
TI  - Suppurative tenosynovitis and septic bursitis.
AB  - Suppurative tenosynovitis and septic bursitis are closed space infections of the
      musculoskeletal system. Appropriate antibiotics in combination with incision and
      drainage are generally recommended. Aggressive surgical management is
      particularly important in tenosynovitis to prevent tendon necrosis. Empiric
      antibiotic coverage should be directed toward staphylococci and streptococci.
      Patient characteristics and epidemiologic exposures may provide clues to unusual
      causative organisms that are occasionally encountered, such as Neisseria
      gonorrhoeae, Pasteurella multocida, atypical mycobacteria, fungi, and
      protothecosis.

PMID- 16297745
TI  - Musculoskeletal gene therapy and its potential use in the treatment of
      complicated musculoskeletal infection.
AB  - Tissue repair is a major issue in orthopedics. Many musculoskeletal tissues,
      including cartilage, meniscus, and the anterior cruciate ligament, heal poorly
      after injury. Recent studies have led to the identification of numerous growth
      factors and other gene products that can promote the regeneration of damaged
      musculoskeletal tissues. In the last century, the discovery and evolving use of
      antibiotics has significantly decreased the prevalence and severity of infectious
      diseases. In many orthopedic scenarios, however, treatment of infections can be
      difficult, and often involves a prolonged course of antibiotics with concomitant
      surgical interventions and loss of tissue. Although studies have demonstrated the
      successful transfer of target genes and the associated manipulation of the
      musculoskeletal tissue environment, researchers have made few attempts designed
      to use gene therapy to treat infectious musculoskeletal diseases in animal
      models. Before it is possible to use gene-based approaches to treat such diseases
      effectively, researchers must perform more studies to investigate the potential
      problems that may arise when using gene therapy in an infectious environment.

PMID- 16297746
TI  - Emergence agitation: time for heavy lifting.

PMID- 16297747
TI  - The effects of low-dose fentanyl on emergence agitation and quality of life in
      patients with moderate developmental disabilities.
AB  - STUDY OBJECTIVE: To analyze whether emergence agitation could be reduced by using
      a low dosage of fentanyl without causing an increase in postoperative adverse
      effects and/or affecting the patient's quality of life after discharge. DESIGN:
      Randomized, controlled crossover trial. SETTING: University medical center.
      PATIENTS: One hundred ten ASA physical status I and II ambulatory patients with
      moderate developmental disabilities who received anesthesia for dental care.
      INTERVENTIONS: During their first visit, patients were randomly treated either
      with a placebo or a 1- to 1.5-microg/kg dose of fentanyl before inserting a
      reinforced laryngeal mask airway and treated with the remaining method during
      their second visit 6 to 12 months later. MEASUREMENTS: Measured variables
      included anesthetic and emergence period, the occurrence of emergence agitation,
      and postanesthetic adverse effects such as nausea and vomiting. After discharge,
      the patient's quality of life was evaluated based on disturbances in daily
      activity, eating habit, and sleeping behavior. Results were analyzed by Student t
      test and McNemar test (P < 0.05). MAIN RESULTS: Between the two treatments, there
      was a significant difference in the frequency of emergence agitation (P = 0.04)
      but no postoperative adverse effects such as postoperative nausea and vomiting.
      We also found no significant disturbances in the patient's quality of life
      according to daily activity, eating habits, or sleeping behavior. CONCLUSION:
      Emergence agitation may be reduced by using 1 to 1.5 microg/kg of fentanyl during
      induction while maintaining anesthesia by sevoflurane in patients with moderate
      developmental disabilities undergoing dental care, without causing an increase in
      postoperative adverse effects and affecting the patient's life quality after
      discharge.

PMID- 16297748
TI  - Intraoperative myocardial ischemia in peripheral vascular surgery: general
      anesthesia vs combined sciatic and femoral nerve blocks.
AB  - STUDY OBJECTIVE: The aim of this study was to compare the frequency of
      intraoperative myocardial ischemia in lower extremity vascular surgery with
      general anesthesia vs regional anesthesia via combined sciatic and femoral nerve
      blocks. DESIGN: This is a prospective, randomized study. SETTING: This study was
      set at an academic medical center. PATIENTS: The study included 50 patients
      scheduled for elective lower extremity vascular surgery. INTERVENTIONS: Patients
      in group 1 received balanced general anesthesia, whereas patients in group 2
      received combined sciatic and femoral nerve blocks with 40 mL of 0.375%
      bupivacaine. Monitoring included a radial artery catheter and multilead, dual
      channel electrocardiogram with computerized ST-segment analysis. Blood pressure
      and heart rate variations were maintained within 10% of preoperative values by
      adjusting anesthetic depth, fluid replacement, and vasoactive drug dosages.
      MEASUREMENTS AND MAIN RESULTS: An ST-segment depression of at least 1 mm or
      elevation of at least 2 mm lasting for more than 1 minute was considered a
      significant episode of myocardial ischemia. Intraoperative hemodynamic data and
      the frequency of significant ST-segment change episodes were recorded. The number
      of patients with ischemic episodes and the total number of these episodes were
      lower in group 2 than in group 1 (1 patient vs 7 patients, P = 0.02; and 2 vs 14
      episodes, P = 0.04). No significant difference was found between groups 1 and 2
      regarding systolic or diastolic arterial pressures, or heart rate. CONCLUSION:
      Compared with general anesthesia, combined sciatic and femoral nerve blocks
      reduce the frequency of intraoperative myocardial ischemia in patients undergoing
      lower extremity vascular surgery.

PMID- 16297749
TI  - Nitrogen accumulation during closed circuit anesthesia depends on the type of
      surgery.
AB  - STUDY OBJECTIVE: The aim of this study is to test the hypothesis that the amount
      of nitrogen that accumulates within the closed breathing system would be greater
      during open abdominal surgery than during superficial surgery with small wounds.
      DESIGN: Prospective, comparative study. SETTING: Operating rooms of a university
      hospital. PATIENTS: Fourteen American Society of Anesthesiologists physical
      status I and II adult patients scheduled for abdominal surgery (n = 7) or
      tympanoplasty (n = 7). INTERVENTIONS: After induction of anesthesia and
      endotracheal intubation, the patients were denitrogenated for 30 minutes using
      100% oxygen at a fresh gas flow of 10 L/min. The breathing system was then closed
      and patients were anesthetized using 60% xenon in oxygen, supplemented with
      epidural anesthesia in the abdominal surgery group and sevoflurane in the
      tympanoplasty group. MEASUREMENTS: Nitrogen concentration in the breathing system
      was determined by gas chromatography immediately before and 2 hours after the
      breathing system was closed. MAIN RESULTS: The median (range) increase in
      nitrogen concentration during the 2-hour period of closed circuit anesthesia was
      greater in the abdominal surgery patients than in the tympanoplasty patients
      (6.5% [4.0%-10.2%] vs 2.5% [1.4%-8.4%], P = 0.035, Mann-Whitney U test).
      CONCLUSIONS: The amount of nitrogen accumulation during closed circuit anesthesia
      is greater during open abdominal surgery than in superficial surgery such as
      tympanoplasty. We postulate that during open abdominal surgery, nitrogen in the
      ambient air enters the body across the peritoneum and then diffuses into the
      alveoli to be exhaled.

PMID- 16297750
TI  - Influence of bispectral index monitoring on decision making during cardiac
      anesthesia.
AB  - STUDY OBJECTIVE: To assess bispectral index (BIS) monitoring on decision making
      during cardiac surgery with cardiopulmonary bypass (CPB) by measuring the number
      of preset standardized comments with and without knowing the BIS value and by
      classifying the interventions following the BIS data. DESIGN: Prospective,
      randomized study. SETTING: University Hospital. PATIENTS: One hundred twenty-one
      patients scheduled for elective cardiac surgery (89 coronary patients, 24 valve
      replacement patients, and 8 valve replacement and coronary surgery).
      INTERVENTIONS: Patients were divided into 3 groups. An observing anesthesiologist
      recorded on a special form ("parallel" anesthesia record) data from the devices
      of the workstation and the BIS monitor. Conditions in which BIS monitoring was
      subjectively considered that might have been useful in anesthetic decision making
      were recorded as "events." In group A (36 patients), the responsible
      anesthesiologist had continuous access to BIS information. In group B (44
      patients), intraoperative anesthetic management was "blinded" to BIS values,
      whereas in group C (41 patients), the anesthesiologist observing the BIS monitor
      was free to inform the attending anesthesiologist about the BIS score. The number
      of events was considered as negatively reflecting the quality of the clinical
      course of a patient. The reduction of events was considered as improvement in
      decision making. All patients received the same anesthetic regimen (propofol +
      remifentanil). Monitoring was equal in all cases. Mild hypothermic CPB was
      applied in 73 patients. Statistical analysis used 1-way analysis of variance,
      Student 2-tailed t test, and chi2 analysis. MAIN RESULTS: Patient demographic
      data, underlying pathology, operation performed, hypothermia application, times
      of anesthesia, duration of operation, and CPB were similar in the 3 groups. In
      group B, the BIS value was considered by the observer as useful to know in 220
      events (5.00 +/- 1.58 per patient). In group C, the BIS value was considered by
      the observer as useful to know in 143 events (3.49 +/- 1.31 per patient, P <
      0.001) and, at the same time, the attending anesthesiologist was informed about
      BIS. In 112 (78.3%) cases, measures were taken. Titration of anesthetic drugs was
      done in 79 (70.5%) patients, whereas titration of vasoactive drugs was done in 9
      (8.0%) patients, titration of both in 13 (11.6%) patients, and other diagnostic
      or corrective actions in 11 (9.8%) patients. Distributions of BIS values did not
      differ statistically (39.19 +/- 10.32, 37.38 +/- 10.21, and 38.29 +/- 10.01 in
      group A, group B, and group C, respectively). "Zenith" and "nadir" BIS values
      after induction also did not differ statistically. Awakening and extubation times
      were similar in both groups. CONCLUSIONS: Subjectivity, although reduced as much
      as possible, can play a confining role in the value of our results. The
      usefulness of BIS monitoring is shown by the fact that BIS data resulted in
      corrective measures. Attending anesthesiologist's actions, based on BIS
      information, reduced the events in group C.

PMID- 16297751
TI  - Effect of 2 anesthetic techniques on the postoperative proinflammatory and anti
      inflammatory cytokine response and cellular immune function to minor surgery.
AB  - STUDY OBJECTIVE: The aim of this study was to investigate the influence of 2
      established anesthetic techniques: total intravenous anesthesia and balanced
      inhalation anesthesia (BAL) on the perioperative-induced changes of peripheral
      blood mononuclear cells (PBMCs), changes in lymphocyte subsets, and the balance
      of proinflammatory and anti-inflammatory cytokines. DESIGN: This is a
      prospective, randomized, clinical comparison study. SETTINGS: This study was set
      at a university hospital. PATIENTS: This study involved 50 patients with American
      Society of Anesthesiologists physical status I who were scheduled for elective
      minimal invasive partial diskectomy. INTERVENTIONS: There was no intervention
      involved in this study. MEASUREMENTS: Changes in differential counts, lymphocyte
      subsets, and proliferation rates were determined before surgery and in the early
      postoperative period. Plasma concentrations of proinflammatory cytokines (IL-2,
      IL-6, IL-12, interferon gamma) and anti-inflammatory cytokines (IL-10, IL-1RA,
      transforming growth factor beta), and plasma concentrations of cortisol,
      epinephrine, and norepinephrine were measured before, during, and after surgery.
      MAIN RESULTS: Absolute number of CD3+, CD4+, and CD8+, and expression of HLA-DR
      and activation marker CD25+, CD26+, and CD69+ decreased more in response to
      surgery after BAL. Changes in distribution of T-lymphocyte cells seem to be in
      part related to severe postoperative pain. Plasma concentration of IL-6
      significantly increased during and after surgery with BAL without relation to
      pain. CONCLUSION: Anesthetic management may have varying influences on the
      postoperative immune response. Surgery-induced inflammatory response and
      alteration in cell-mediated immunity seem to be more pronounced after BAL. These
      effects were attributed to the enhanced stress response after BAL.

PMID- 16297752
TI  - Advancing an epidural catheter 10 cm then retracting it 5 cm is no more effective
      than advancing it 5 cm.
AB  - STUDY OBJECTIVE: To determine whether threading an epidural catheter 10 cm then
      retracting it 5 cm affects its intravascular placement and paresthesias. DESIGN:
      Prospective randomized study. SETTING: Labor and Delivery Unit, University
      Medical Center. PATIENTS: Eighty parturients. INTERVENTIONS: All patients
      received epidural anesthesia. Patients were randomized to 1 of 2 groups:
      threading the epidural catheter 5 cm (5-cm group) or threading the epidural
      catheter 10 cm and retracting 5 cm (10-cm group). In the 10-cm group, the
      epidural catheter was threaded 10 cm and pulled back 5 cm. In the 5-cm group, the
      epidural catheter was threaded 5 cm. MEASUREMENTS AND MAIN RESULTS: Placement of
      the epidural catheter intravascularly, the presence of a paresthesia, and
      bilateral sensory levels were measured. There was no difference in the frequency
      of intravascular placement between 10- and 5-cm groups, 10.2% vs 7.5%,
      respectively. Although not statistically significant, there was a trend toward a
      higher frequency of paresthesia in the 10-cm group, 15.4% vs 7.5%, and a lower
      frequency of uneven sensory levels in the 10-cm group, 15% vs 2.6%. CONCLUSIONS:
      There is no clear clinical benefit or disadvantage to threading an epidural
      catheter 10 cm into the epidural space then withdrawing it 5 cm. Further study is
      warranted.

PMID- 16297753
TI  - Comparison of 2 concentrations of levobupivacaine in postoperative patient
      controlled epidural analgesia.
AB  - STUDY OBJECTIVES: To evaluate the quality of analgesia and the incidence of side
      effects of 2 different concentrations of levobupivacaine given as an equal
      milligram-bolus dose (5 mg) via patient-controlled epidural analgesia after
      abdominal surgery. DESIGN: Prospective, randomized, blinded study. SETTING:
      Postanesthesia care unit and surgical wards of a university hospital. PATIENTS:
      Forty-nine patients (41 with complete file) undergoing major lower abdominal
      surgery. INTERVENTIONS: The patients were randomly assigned to 2 groups: 1.5
      mg/mL (bolus 3.3 mL, lockout 20 minutes, n = 26) and 5 mg/mL (bolus 1 mL, lockout
      20 minutes, n = 23). The epidural catheter was inserted in the low thoracic level
      (T9-T12) before induction of a standardized general anesthesia technique.
      MEASUREMENTS: Demography, upper sensory block, visual analog scale scores at rest
      and after coughing, levobupivacaine and rescue morphine consumption, motor
      blockade, hemodynamics, postoperative nausea and vomiting, sedation, and patient
      satisfaction were recorded within the first 48 hours. MAIN RESULTS: Both groups
      were similar with regard to demographics, upper level of sensory blockade (T8),
      and visual analog scale pain scores at rest and after coughing, as well as
      levobupivacaine and subcutaneous rescue morphine consumption. Motor blockade in
      the lower limbs was very low in both groups. Arterial blood pressure was slightly
      lower in the 5 mg/mL group during the first 24 hours (P = 0.052). Five patients
      in the 1.5 mg/mL and 7 in the 5 mg/mL group had postoperative nausea and vomiting
      (P = 0.43). No other side effects were recorded, and all of the patients were
      satisfied. CONCLUSIONS: Administering the same dose of levobupivacaine in either
      a low or high concentration via patient-controlled epidural analgesia mode
      provides an equal quality of analgesia with no difference in the incidence of
      side effects.

PMID- 16297754
TI  - The frequency and timing of respiratory depression in 1524 postoperative patients
      treated with systemic or neuraxial morphine.
AB  - STUDY OBJECTIVE: To describe the frequency and timing of intravenous patient
      controlled analgesia (IV-PCA) or neuraxial morphine-induced postoperative
      respiratory depression. DESIGN: Audit of data captured by routine quality
      assurance of the acute pain protocols that were implemented by nurses performing
      routine postoperative care. SETTING: The surgical wards of a university
      affiliated, 700-bed, tertiary hospital. PATIENTS AND INTERVENTIONS: In real time,
      the data of all patients enrolled into our Acute Pain Service (APS) were entered
      and stored in the APS database. Thereafter, patients who had received IV morphine
      via a PCA device or neuraxial morphine between January 1999 and December 2002
      were isolated. From this subset, all patients in whom a respiratory rate (RR)
      less than 10 breaths per minute was recorded were retrieved. MEASUREMENTS AND
      MAIN RESULTS: From a total of 4500 patients, IV or neuraxial morphine was
      administered to 1524 patients. Eighteen (1.2%) cases of an RR less than 10
      breaths per minute were recorded (13 patients, 4 patients, and 1 patient in the
      IV-PCA, daily epidural morphine, and single-dose intrathecal morphine groups,
      respectively). A direct correlation between intraoperative fentanyl
      administration and postoperative respiratory depression was demonstrated between
      the IV-PCA (P = 0.03) and epidural groups (P = 0.05). The time from IV-PCA
      initiation or last neuraxial morphine administration until the diagnosis of
      respiratory depression ranged between 2 hours and 31.26 hours and 2 hours and
      12.15 hours, respectively. Ten (55.6%) patients received naloxone. CONCLUSION:
      Morphine-induced respiratory depression may occur at any time during the APS
      admission. However, the optimal frequency of intermittent RR monitoring is
      unknown. Furthermore, because multiple variables (age, sex, prior opioid
      administration, site of operation) may affect morphine-induced respiratory
      depression, further investigation must be performed to determine the ideal
      monitoring protocol.

PMID- 16297755
TI  - Nitrous oxide anxiolysis for elective cesarean section.
AB  - STUDY OBJECTIVE: To determine if inhaled 40% nitrous oxide (N(2)O) via facemask
      is an effective anxiolytic in women undergoing elective cesarean section under
      spinal anesthesia. STUDY DESIGN: Prospective, randomized, double-blinded study.
      SETTING: Tertiary-care women's hospital. PATIENTS: Sixty American Society of
      Anesthesiologists physical status I and II patients scheduled for elective
      cesarean section under spinal anesthesia. INTERVENTIONS: Patients were randomized
      to 2 groups to receive either 100% O2 via facemask or 40% N2O in O2 via facemask.
      MEASUREMENTS: Vital signs (blood pressure, heart rate, and oxygen saturation) and
      measured variables (visual analog scale [VAS] anxiety, VAS pain, and sedation
      scores) were obtained at specific periods during the procedure (preoperatively,
      entering the operating room, spinal injection, skin incision, uterine incision,
      delivery, and at the conclusion of the surgical procedure). In addition, surgical
      time and delivery time, mean dose and percentage of patients requiring ephedrine
      or phenylephrine boluses, the emesis rate, and Apgar scores were measured. MAIN
      RESULTS: No differences were noted with respect to maternal mean blood pressure,
      heart rate, pulse-oximeter oxygen saturation, and sedation or VAS pain scores
      during the measured periods. No differences were noted in surgical and delivery
      times, mean dose, or percentage of patients who required ephedrine or
      phenylephrine to maintain maternal blood pressure, the emesis rate, or 1- and 5
      minute Apgar scores. Mean anxiety scores for the N2O group were significantly
      lower at the time of spinal injection, skin incision, and uterine incision.
      Multivariate analysis of variance for high-anxiety patients (> or =50 VAS)
      revealed significantly lower VAS scores in the N2O group, compared with the O2
      group again at spinal injection, skin incision, and uterine incision.
      CONCLUSIONS: Inhaled 40% N2O via facemask provides effective anxiolysis in women
      undergoing elective cesarean section under spinal anesthesia in patients with
      high anxiety (> or =50 VAS) at the time of spinal injection, skin incision, and
      uterine incision.

PMID- 16297756
TI  - Comparison of conscious sedation for oocyte retrieval between low-anxiety and
      high-anxiety patients.
AB  - STUDY OBJECTIVE: To investigate the correlation among the level of anxiety, the
      intravenous propofol requirement for conscious sedation, and recovery profile in
      in vitro fertilization patients. DESIGN: Prospective, randomized, double-blinded
      study. SETTING: Operating room of tertiary-care university hospital. PATIENTS:
      One hundred fifty consecutive women scheduled for oocyte retrieval under
      conscious sedation. INTERVENTIONS: Anxiety scores were separately measured by an
      anesthesiologist who was not involved in sedation. The patients were divided into
      2 groups, high-anxiety and low-anxiety, as determined by using the median of
      anxiety VAS scoring for assessment of preoperative anxiety (4.0 cm). The subjects
      were collected, 76 in high-anxiety group and 74 in low-anxiety group.
      MEASUREMENTS: An infusion of propofol with a preset target concentration of 2.5
      microg/mL(-1) was started until the patient had reached and maintained a sedation
      level of 3 on a 5-point sedation scale. Hemodynamic variables were recorded by
      using standard monitors. The scorings of sedation, operability, and satisfaction
      were assessed by one of the investigator-anesthesiologists. Data of induction
      quality and concentration of propofol were obtained from Target-Controlled
      Infusion system that runs on a microcomputer connected to an infusion pump
      (Becton-Dickinson infusion system, Le Grande chemin, France). Recovery data were
      measured in the recovery room. MAIN RESULTS: The high-anxiety group required more
      for the induction of sedation and a larger amount of total dosage of propofol for
      sedation, as compared with the low-anxiety group. The concentrations of propofol
      on the Target-Controlled Infusion at sedation level 3 of the high-anxiety group
      were significantly higher than those of the low-anxiety group. Context-sensitive
      half time of high-anxiety group was also longer than that of the low-anxiety
      group. The postoperative pain score of the high-anxiety group was higher than
      that of the low-anxiety group. Increased preoperative anxiety was significantly
      correlated with postoperative wound pain (r = 0.240, P = 0.009) and previously
      experienced pain on same procedure (r = 0.252, P = 0.031), but not with pain on
      propofol injection (r = -0.05, P = 0.58). CONCLUSIONS: The high-anxiety group
      needs more sedative requirement of propofol for conscious sedation than the low
      anxiety group. Thus, we suggest that propofol dose for such sedation must take
      into account the individual patient's anxiety level when propofol is administered
      by an anesthesiologist for oocyte retrieval.

PMID- 16297757
TI  - Assessment of psychological tension after premedication by measurement of
      salivary chromogranin A.
AB  - STUDY OBJECTIVE: Although some sedatives or analgesics are commonly used for
      premedication to reduce psychological tension before surgery or anesthesia, it
      remains unclear which drug is more suitable. Because salivary chromogranin A is a
      reliable index for estimating psychological tension, this variable was measured
      during the perioperative period after premedication. DESIGN: Prospective,
      randomized control study. SETTING: Operating room at a general hospital.
      PATIENTS: Thirty adult female patients undergoing abdominal total hysterectomy
      were randomly assigned to 3 groups of 10 patients each. INTERVENTIONS: On the day
      before surgery, saliva was collected, and 0.1 mg/kg of midazolam (midazolam
      group) or 0.02 mg/kg of butorphanol (butorphanol group) was injected
      intramuscularly 30 minutes before entering the operating rooms. For the control
      group, no premedication was performed. Saliva was collected as the patient
      entered the operating room and then the patient received an epidural catheter
      insertion followed 5 minutes later by collection of the saliva. MEASUREMENTS AND
      MAIN RESULTS: Salivary chromogranin A was assayed using a radioimmunoassay, and
      revised values calculated from the protein concentration of the saliva were
      regarded as data. Revised salivary chromogranin A levels increased in the control
      and butorphanol groups at the time of entrance to the operating room and after
      epidural treatment compared with the value of the day before surgery, whereas it
      did not change statistically in the midazolam group. CONCLUSIONS: From the
      standpoint of reducing psychological tension before surgery or anesthesia,
      midazolam as a sedative may be more suitable for premedication.

PMID- 16297758
TI  - Orthotopic liver transplantation in a malignant hyperthermia susceptible patient.
AB  - We present a patient with hepatitis C and D and hepatocellular carcinoma who
      underwent preoperative evaluation for orthotopic liver transplantation. In his
      past medical history, he reported a life-threatening event during tonsillectomy
      in 1975. Intubation was impossible due to extreme jaw muscle tension, followed by
      excessive elevation in body temperature, tachycardia, and coma for a few days. We
      evaluated him for malignant hyperthermia, according to the European Malignant
      Hyperthermia Group Protocol, and found him highly positive in both the halothane
      and caffeine test, respectively. Three months later, we performed an orthotopic
      liver transplantation. During retransplantation 4 years later, due to ischemic
      type biliary lesions, he suffered massive intraoperative bleeding. Blood
      products, as well as coagulation factors and aprotinin, were well tolerated.
      Anesthesia was performed in a trigger-free total intravenous technique without
      dantrolene prophylaxis, but dantrolene was readily available in sufficient
      quantities in the operating room. The patient did not encounter a malignant
      hyperthermia crisis in either perioperative period.

PMID- 16297759
TI  - The human error: delayed diagnosis of intravascular loss of guidewires for
      central venous catheterization.
AB  - We report three recent cases in which there was intravascular loss of the entire
      guide wire. In one case, this loss was discovered more than three months after
      the patient's procedure. In another case, the loss was detected one month later,
      and in the third case, four days was the interval of the loss. We discuss the
      problems of human error and failure of diagnosis, both of which were responsible
      for serious sequelae.

PMID- 16297760
TI  - General anesthesia for patient with type III homocystinuria (tetrahydrofolate
      reductase deficiency).
AB  - Homocystinuria, a rare autosomal recessive genetic disease, is generally
      classified into 3 types (types I-III). Extremely rare type III is from a defect
      of the enzyme tetrahydrofolate reductase which converts homocysteine to
      methionine. The anesthetic problem of type III homocystinuria is the elevation of
      serum homocysteine and the deficiency of essential amino acid methionine, which
      result in the perioperative thromboembolic events and nitrous oxide-induced
      neurological impairment. We provided successful anesthetic management for a
      patient with type III homocystinuria, during which we were careful to take
      measures against perioperative thromboembolism and did not use nitrous oxide.

PMID- 16297761
TI  - Presentation of dapsone-induced methemoglobinemia in a patient status post small
      bowel transplant.
AB  - Methemoglobinemia, an uncommon hemoglobinopathy, affects oxygen transport,
      causing tissue hypoxia. In the perioperative period, methemoglobinemia is often
      overlooked as a cause of low oxygen saturation, often mistaken for the more
      common causes of hypoxia, such as atelectasis, pulmonary edema, or pulmonary
      embolus, among other causes of respiratory failure. Most cases of
      methemoglobinemia in the perioperative period are precipitated by local
      anesthetics, especially benzocaine. Dapsone, a sulfone antibiotic, is used for
      prophylaxis against Pneumocystis carinii pneumonia in immunosuppressed patients.
      It is commonly used in organ transplant patients, especially those intolerant to
      sulfa. With the expansion of organ transplantation and improved long-term
      survival of these patients, presentation of status post organ transplant patients
      for surgery will inevitably increase. We report a case of dapsone-induced
      methemoglobinemia observed in a status post small bowel transplant patient in the
      postanesthesia care unit.

PMID- 16297762
TI  - Communion wafer impeding transesophageal echocardiographic imaging.

PMID- 16297763
TI  - Salt-sensitive hypertension, Na+/Ca2+ exchanger, and vascular smooth muscle.
AB  - Hypertension is the most common chronic disease and is the leading risk factor
      for death caused by stroke, myocardial infarction, and end-stage renal failure.
      The critical importance of excess salt intake in the pathogenesis of hypertension
      is widely recognized. However, the molecular mechanisms underlying salt-sensitive
      hypertension remain obscure. Recent studies using selective Na(+)/Ca(2+)
      exchanger (NCX) inhibitors and genetically engineered mice provide compelling
      evidence that salt-sensitive hypertension is triggered by Ca(2+) entry through
      NCX type 1 (NCX1) in arterial smooth muscle. Cardiotonic steroids, such as
      endogenous ouabain, which may contribute to the pathogenesis of salt-sensitive
      hypertension, seem to be necessary for NCX1-mediated hypertension. These findings
      have enabled us to explain how high salt intake leads to hypertension and further
      to describe the potential of vascular NCX1 as a new therapeutic or diagnostic
      target for salt-sensitive hypertension.

PMID- 16297764
TI  - Nicotinamide adenine dinucleotide phosphate oxidase: a promiscuous therapeutic
      target for cardiovascular drugs?
AB  - The increased expression and activity of the nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase complex has emerged as a major common factor in the
      etiology of all forms of cardiovascular diseases since the upregulation of
      intravascular NADPH oxidase results in the formation of superoxide (O(2)(-)),
      which in turn promotes vasculopathy. An ever-increasing number of drugs commonly
      used in cardiovascular medicine have been shown to influence NADPH oxidase
      expression and activity. These include nitric oxide donors, nitroaspirin,
      eicosanoids, phosphodiesterase inhibitors, corticosteroids, antioxidants, and
      specific inhibitors. The objective of this review is to discuss these drugs in
      relation to the mechanisms underlying their effects on NADPH oxidase activity and
      the expression and therapeutic implications of these effects.

PMID- 16297765
TI  - Bcl-2 regulation of mitochondrial energetics.
AB  - Recent data suggest that in addition to regulating apoptosis, Bcl-2 (an anti
      apoptotic protein overexpressed in B-cell lymphoma) and Bcl-2 family members also
      regulate mitochondrial and cell physiology. t-Bid, a Bcl-2 family member, has
      been shown to modulate reorganization of mitochondrial cristae. Bcl-2 appears to
      regulate voltage-dependent anion channel permeability, which has important
      consequences for mitochondrial transport of adenine nucleotides, Ca(2+), and
      other metabolites. BAD, a pro-apoptotic Bcl-2 family member, is required for the
      binding of glucokinase to a mitochondrial complex, and BAD null mice have altered
      glucose homeostasis. It has been suggested that Bcl-2 family members may regulate
      important mitochondrial/cell functions and serve as sentinels to detect
      abnormalities in these pathways and, when the abnormalities are severe enough, to
      initiate or facilitate cell death. Understanding the physiologic processes
      controlled by Bcl-2 will be important in understanding cell regulation, and it
      may also provide new insights into the regulation of apoptosis.

PMID- 16297766
TI  - Apolipoprotein A-I mimetic peptides: potential role in atherosclerosis
      management.
AB  - Atherothrombotic vascular disease continues to be a leading cause of morbidity
      and mortality in much of the world. Although a healthy lifestyle and low-density
      lipoprotein cholesterol lowering significantly reduce cardiovascular morbidity
      and mortality, substantial number of adverse vasoocclusive events continue to
      occur. These realities have brought attention to additional therapies that could
      further reduce cardiovascular events. High-density lipoprotein
      (HDL)/apolipoprotein A-I (apo A-I)-based therapies are a potential therapeutic
      strategy against atherothrombotic vascular disease because of the known inverse
      relationship between HDL cholesterol and coronary heart disease, favorable and
      pleotrophic biologic effects of HDL/apo A-I, results of preclinical experimental
      studies, and emerging proof of concept in clinical studies. A variety of HDL/apo
      A-I-based therapies are currently under investigation, including synthetic
      peptides that mimic the function of HDL. Such apo A-I mimetic peptides are the
      focus of this review.

PMID- 16297767
TI  - Tracking stem cells in the cardiovascular system.
AB  - Stem cells are a promising approach to cardiovascular therapeutics. Animal
      experiments have assessed the fate of injected stem cells through ex vivo methods
      on sacrificed animals. Approaches are needed for in vivo tracking of stem cells.
      Various imaging techniques and contrast agents for stem cell tracking will be
      reviewed.

PMID- 16297768
TI  - Regulation of Weibel-Palade body exocytosis.
AB  - Weibel-Palade bodies (WPBs) are endothelial granules that store von Willebrand
      factor (VWF), P-selectin, and other vascular modulators. Endothelial cells
      secrete WPBs in response to vascular injury, releasing VWF, which triggers
      platelet rolling, and externalizing P-selectin, which activates leukocyte
      trafficking. Endothelial exocytosis is one of the earliest responses to vascular
      damage and plays a pivotal role in thrombosis and inflammation. This review
      examines the regulation of WPB exocytosis-the exocytic machinery, activators, and
      inhibitors of exocytosis-and speculates about the development of novel anti
      exocytic drugs.

PMID- 16297769
TI  - The revised ISHLT heart biopsy grading scale.

PMID- 16297770
TI  - Revision of the 1990 working formulation for the standardization of nomenclature
      in the diagnosis of heart rejection.
AB  - In 1990, an international grading system for cardiac allograft biopsies was
      adopted by the International Society for Heart Transplantation. This system has
      served the heart transplant community well, facilitating communication between
      transplant centers, especially with regard to patient management and research. In
      2004, under the direction of the International Society for Heart and Lung
      Transplantation (ISHLT), a multidisciplinary review of the cardiac biopsy grading
      system was undertaken to address challenges and inconsistencies in its use and to
      address recent advances in the knowledge of antibody-mediated rejection. This
      article summarizes the revised consensus classification for cardiac allograft
      rejection. In brief, the revised (R) categories of cellular rejection are as
      follows: Grade 0 R--no rejection (no change from 1990); Grade 1 R--mild rejection
      (1990 Grades 1A, 1B and 2); Grade 2 R--moderate rejection (1990 Grade 3A); and
      Grade 3 R--severe rejection (1990 Grades 3B and 4). Because the histologic sub
      types of Quilty A and Quilty B have never been shown to have clinical
      significance, the "A" and "B" designations have been eliminated. Recommendations
      are also made for the histologic recognition and immunohistologic investigation
      of acute antibody-mediated rejection (AMR) with the expectation that greater
      standardization of the assessment of this controversial entity will clarify its
      clinical significance. Technical considerations in biopsy processing are also
      addressed. This consensus revision of the Working Formulation was approved by the
      ISHLT Board of Directors in December 2004.

PMID- 16297771
TI  - Role of Toll-like receptor-driven innate immunity in thoracic organ
      transplantation.
AB  - Innate immunity represents the first line of defense against microbial invasion.
      Recent studies have determined that a group of germline-encoded receptors, termed
      Toll-like receptors (TLRs), are critical for recognizing foreign motifs on
      microbial organisms and initiating innate responses. An exciting area of research
      has recently linked activation of TLRs on antigen-presenting cells (APCs) to
      effective antigen presentation and activation of naive T cells. Most studies have
      shown that TLR-dependent immune function leads to T-helper 1 (TH1) immunity,
      although evidence also supports that TH2 immune responses may be initiated by TLR
      signaling in certain contexts. In either case, innate immune signaling via TLRs
      leads to a productive adaptive immune response. In contrast to studies in purely
      infectious models, emerging data from experimental and clinical studies have
      provided evidence that TLR immune function is important in acute allograft
      rejection. Specifically, MyD88, an important TLR signal adaptor, was found to be
      critical for the rejection of minor-mismatched skin allografts, and important for
      alloimmune priming and TH1 immunity against fully allogeneic skin grafts.
      Furthermore, a clinical study has shown that recipients with TLR 4 polymorphisms
      associated with endotoxin hyporesponsiveness manifest reduce acute lung allograft
      rejection. Collectively, these studies demonstrate that innate immunity is
      important for alloimmunity. Future therapeutic modalities that target innate
      rather than adaptive immune mechanisms represent a promising avenue for future
      studies in thoracic organ transplantation.

PMID- 16297772
TI  - The prognostic validity of the ventricular evoked response (VER) signals in
      cardiac transplantation.
AB  - INTRODUCTION: Computerized heart allograft rejection monitoring (CHARM) used for
      non-invasive rejection monitoring in heart transplant recipients is based on the
      analysis of ventricular evoked response (VER) signals. The aim of this study was
      to evaluate the prognostic validity of the Tslew(C), a parameter calculated from
      the VER. METHODS: During orthotopic heart transplantation, 2 unipolar fractally
      coated screw-in leads were implanted epimyocardially, one to the left and one to
      the right ventricle, and connected to a telemetric pacemaker. Recordings of
      intramyocardial electrograms were performed routinely at the hospital. Data
      processing was done, artifacts were eliminated, and trend curves of the patients
      were displayed. Tslew(C) was calculated from the tangent of VER and evaluated
      from 105 patients. The patients were divided into survivor and non-survivor
      groups. For statistical analysis, the 2-tailed t-test was performed. RESULTS:
      Patients in the non-survivors group compared with the control group showed a
      significantly lower Tslew(C) in the final follow-up (p < 0.001). The differences
      were even more impressive in patients with recorded intramyocardial electrograms
      30 days before death or with a cardiac reason for death. Tests were performed to
      find an optimal prognostic threshold of the Tslew(C), and the value of 26 mV was
      finally found. CONCLUSION: Tslew(C) can function as prognostic factor after
      orthotopic heart transplantation. Further studies should be initiated to provide
      the prognostic threshold so that patients would not be forced to show up
      routinely every 4 weeks for follow-up visits. Patients would only have to be
      admitted to the hospital if the Tslew(C) were less than this prognostic
      threshold.

PMID- 16297773
TI  - Ten-year follow-up of a randomized trial of pravastatin in heart transplant
      patients.
AB  - BACKGROUND: Outcomes from this trial's first year data demonstrated significant
      benefit in heart transplant patients treated with pravastatin in cholesterol
      levels, survival, rejection with hemodynamic compromise, the development of
      cardiac allograft vasculopathy, and decreased natural killer cell cytotoxicity.
      Other heart transplant studies have shown similar benefit. We now report the 10
      year follow-up of this study. METHODS: Ninety-seven heart transplant recipients
      were randomized to pravastatin (n = 47) or no pravastatin (n = 50) within 2 weeks
      after surgery both in combination with cyclosporine and corticosteroids. Ten-year
      outcomes include survival, cholesterol levels, and development of cardiac
      allograft vasculopathy documented by coronary angiography. RESULTS: Forty-two
      percent of the control patients crossed over to pravastatin treatment during the
      second year of the study, and 81% of the control patients were eventually placed
      on statin therapy by the 10-year follow-up. The control group had subsequent low
      and comparable cholesterol levels in Years 2 to 10 of the study compared with the
      patients originally randomized to pravastatin. Intent-to-treat analysis
      demonstrated that the pravastatin group compared with control had increased 10
      year survival (68% vs 48%, p = 0.026). The 10-year freedom from angiographic
      cardiac allograft vasculopathy and/or death in the pravastatin group was
      significantly greater compared with the control group (43% vs 20%, p = 0.009).
      CONCLUSION: The 10-year follow-up of this study suggests that the use of
      pravastatin in heart transplant patients maintains survival benefit and appears
      to reduce the development of cardiac allograft vasculopathy.

PMID- 16297774
TI  - The impact of donor gender on cardiac peri-transplantation ischemia injury.
AB  - BACKGROUND: Cardiac allografts from female donors have been shown to be
      associated with increased risk of transplant vasculopathy. However, the influence
      of donor gender on peri-transplantation ischemic injury has not been evaluated.
      METHODS: A total of 361 patients (mean age, 52 +/- 10 years) underwent cardiac
      transplantation between January 1998 and December 2002. Patients were divided
      into 4 groups according to their donor-recipient gender status: Group A, male
      male, 156; Group B, male-female, 37; Group C, female-male, 114; and Group D,
      female-female, 54. Serial right ventricular endomyocardial biopsy specimens were
      evaluated for ischemic injury during the first 4 weeks after transplantation.
      RESULTS: Patients were similar in baseline characteristics. An increased
      incidence of ischemic injury complicated by fibrosis (12.9%, p = 0.03) and
      subsequent development of transplant vasculopathy (Kaplan-Meier 6-year freedom
      from vasculopathy, 53.4%; p = 0.012) was noted in Group D. No survival difference
      was observed among the 4 groups, however. In Group D (F-F), 2 patients underwent
      retransplantation and 2 patients underwent revascularization. CONCLUSIONS: The
      transplantation of a female cardiac allograft into a female recipient is
      associated with increased risk of ischemic injury complicated by fibrosis and
      subsequent transplant vasculopathy.

PMID- 16297775
TI  - A decade experience of cardiac retransplantation in adult recipients.
AB  - BACKGROUND: Cardiac retransplantation is considered to be the best therapeutic
      option for a failing cardiac allograft. However, poor outcomes with
      retransplantation have previously been reported, a factor that raises important
      ethical, logistic and financial issues given the limited organ donor supply.
      METHODS: Seven hundred sixty-six adult patients underwent cardiac transplantation
      for end-stage heart failure at our institution from 1992 to 2002. Of these, 41
      (5.4%) were retransplants. Variables examined included recipient and donor
      demographics, indications for retransplant, comorbidities, cytomegalovirus (CMV)
      serology status, left ventricular assist device use before transplant, donor
      ischemic time, rate of early mortality (within 30 days), and post-transplantation
      survival rate. RESULTS: Indications for cardiac retransplant were transplant
      related coronary artery disease in 37, acute rejection in 3, and other causes in
      1. The mean interval between transplantation and retransplantation was 5.9 +/-
      3.4 years. Baseline characteristics such as recipient age, gender, CMV serology
      status, and donor age were similar in the primary transplant and retransplant
      groups. Early mortality after transplantation was comparable between the 2
      groups, but post-transplant survival was significantly lower in retransplant
      patients compared with primary transplants with 1-, 3-, 5-, and 7-year actuarial
      survival rates of 72.2%, 66.3%, 47.5%, and 40.7% vs. 85.1%, 79.2%, 72.9%, and
      66.8%, respectively (p < 0.001). CONCLUSIONS: Cardiac retransplantation offers
      short-term outcomes similar to primary transplantation but lower long-term
      survival rates. Non-retransplant surgical options should also be considered in
      these patients. Careful patient selection and risk-assessment is necessary to
      govern appropriate allocation of limited donor organs.

PMID- 16297777
TI  - Reversibility of cardiac cachexia after heart transplantation.
AB  - BACKGROUND: Cachexia is an independent risk factor for mortality in patients with
      chronic heart failure and increases mortality even after heart transplantation
      (HTx). We aimed to determine whether cardiac cachexia is reversible after HTx,
      and investigated differences specific to gender. METHODS: We prospectively
      examined 106 patients before and serially 3, 6, 12 and 24 months after HTx (18
      women, 88 men; median age at transplantation 53.7 +/- 9.7 years; n = 68 dilative
      cardiomyopathy, n = 33 coronary heart disease, n = 5 other origin of heart
      failure). Patients were sub-grouped as underweight (body mass index [BMI] < or
      =21 kg/m2, n = 15), normal weight (BMI 21 to 27 kg/m2, n = 64) and obese (BMI >
      or =27 kg/m2, n = 27). RESULTS: Body weight increase was restricted to
      underweight patients: at 3 months (+6.8% vs pre-transplant weight); at 6 months
      (+11.3%), at 12 months (+15.6%); and at 24 months (+17.7%, all p < or = 0.03).
      The entire population had weight loss at 3 months (-2.9%), but had weight gain at
      6 (+2.5%), 12 (+6.1%, all p < or = 0.02) and 24 months (+1.3%, p = 0.44). A lower
      BMI before HTx correlated significantly with greater weight increase after HTx at
      every follow-up time-point (r = 0.55; p < 0.001). There were no gender-specific
      differences for BMI or weight change. Weight loss within 3 months after HTx was
      associated with higher mortality during 4 years of follow-up. CONCLUSIONS: Weight
      gain after HTx is particularly strong in underweight patients, and the increased
      cardiac function causes the cessation of cachexia. The weight increase of the
      entire heart transplant population is partially an effect of reversibility of
      cachexia and not affected by gender.

PMID- 16297776
TI  - Influence of the exercise protocol on peak VO2 in patients after heart
      transplantation.
AB  - BACKGROUND: The protocol and the duration of an exercise test have considerable
      influence on peak oxygen consumption (VO2). On a bicycle ergometer, the use of a
      ramp protocol with a target exercise duration of 8 to 12 minutes is recommended
      to reliably measure maximal oxygen uptake. Because of cardiac denervation, heart
      transplant recipients have a delayed heart rate adaptation to exercise, and
      oxygen uptake kinetics are altered. METHODS: We investigated whether the rate of
      workload increase during exercise testing would influence peak VO2 after heart
      transplantation. Two symptom-limited exercise tests, applying a ramp and a 3
      minute step protocol were effectuated on a bicycle ergometer. RESULTS: Seventeen
      patients (14 men, 3 women), mean age 58.4 +/- 12.7 years, at 64.5 +/- 26.7 months
      post-transplant participated in the study. No statistically significant
      differences between the 2 protocols were found regarding total exercise duration
      until exhaustion (8:42 +/- 2:09 vs 8:48 +/- 2:27 minutes, p = 0.705), maximal
      workload reached (117.9 +/- 42.6 vs 106.4 +/- 40.5 W; p = 0.055), peak heart rate
      (135.8 +/- 11.6 vs 131.2 +/- 14.8 beats/min.; p = 0.061), and peak VO2 (20.9 +/-
      5.2 vs 20.5 +/- 5.9 ml/kg/min; p = 0.538). CONCLUSIONS: Peak VO2 seems
      insensitive to a stepwise or ramping exercise protocol in heart transplant
      patients when the workload increments are chosen in a way that a total exercise
      time of 8 to 12 minutes is achieved. Both protocols can therefore be applied to
      evaluate peak VO2.

PMID- 16297778
TI  - Outcome of heart transplantation in patients with amyloid cardiomyopathy.
AB  - BACKGROUND: We retrospectively reviewed the United Network for Organ Sharing
      (UNOS) database to assess the survival of patients with amyloidosis who were
      treated by heart transplantation. METHODS: Over a 15-year period, 69 patients had
      received orthotopic heart transplants and were entered into the database with the
      diagnosis of amyloidosis. The cohort consisted of 38 men and 31 women. Mean age
      was 51 years. RESULTS: There were 5 operative deaths and 29 late deaths at a mean
      follow-up of 40 months. Nine patients died of amyloid-related complications, and
      one developed graft vasculopathy and was retransplanted. CONCLUSIONS: Survival
      was influenced by recipient's sex (1-year survival 84% for men vs 64% for women,
      p = 0.003) but not by transplant era, ischemia time, or UNOS status.

PMID- 16297779
TI  - The impact of CytoGam on cardiac transplant recipients with moderate
      hypogammaglobulinemia: a randomized single-center study.
AB  - BACKGROUND: We have previously shown that the preemptive use of cytomegalovirus
      (CMV) immunoglobulin (Ig) replacement (CytoGam) decreases the incidence of
      opportunistic infections in cardiac transplant recipients with severe
      hypogammaglobulinemia. However, the impact of Ig replacement in moderately
      hypogammaglobulinemic patients is unknown. METHODS: Periodic monitoring of the
      IgG levels was done in 300 heart transplant recipients. Moderate
      hypogammaglobulinemia (IgG, 350-500 mg/dl) developed in 56 patients (18.6%).
      Thirty-three patients declined randomization but agreed to have their IgG levels
      monitored. Twenty-three patients were randomized to placebo (n = 10) or CytoGam
      (n = 13) at 105 +/- 63 days after transplantation. RESULTS: The baseline
      characteristics were similar. A significant reduction in CMV infection was noted
      in the CytoGam Group compared with the Placebo Group (15.4% [2/13] vs 60% [6/10],
      p = .039). Among patients who declined randomization, CMV infection developed in
      13 (39.4%) of 33, and 6 (46.1%) of the 13 progressed to severe
      hypogammaglobulinemia. A trend for reduction in the average episodes of > or
      =grade 2 rejection during the 6-month period after randomization was noted in the
      CytoGam group (0.4 +/- 0.6 vs 1.4 +/- 1.3, p = 0.065). CONCLUSIONS: The
      preemptive use of CytoGam decreases the incidence of CMV infection in patients
      with moderate hypogammaglobulinemia. A larger randomized study is needed to
      substantiate these results.

PMID- 16297780
TI  - The importance of 24 hour ambulatory blood pressure monitoring after thoracic
      organ transplantation.
AB  - BACKGROUND: Hypertension is a significant complication after thoracic organ
      transplantation. In the non-transplant population, 24-hour ambulatory blood
      pressure monitoring (24ABPM) is useful in the diagnosis of white-coat
      hypertension, the assessment of resistant hypertension, and the monitoring of
      anti-hypertensive therapy. The loss of nocturnal reductions in blood pressure is
      associated with hypertensive end-organ damage. This study investigated the role
      of 24ABPM after orthotopic cardiac transplantation. METHODS: Thirty-three
      transplant recipients underwent 24ABPM. Clinical blood pressure (CPB) was
      measured by using a sphygmomanometer before 24ABPM. Clinical data were collected
      and analyzed by a single observer with p values of less than 0.05 being taken as
      significant. RESULTS: The incidence of hypertension (diastolic pressure > 90 mm
      Hg) in the CPB and 24ABPM groups was 33% and 52% (p =0.002). Thirty-two percent
      of recipients who were normotensive by clinical measurement were found to be
      hypertensive after 24ABPM. The converse was true in 1 case. We identified no
      specific risk factors for 24ABPM hypertension. One recipient failed to complete
      the 24-hour monitoring period. CONCLUSION: This study demonstrates that
      conventional blood pressure monitoring underestimates the incidence of post
      transplantation hypertension. Twenty-four hour ambulatory blood pressure
      monitoring is well tolerated and may improve the management of post
      transplantation hypertension. White-coat hypertension is an uncommon diagnosis
      after cardiac transplantation, and those recipients who are hypertensive in the
      clinic setting should be considered true hypertensives.

PMID- 16297781
TI  - Exercise limitation in trained heart and kidney transplant recipients: central
      and peripheral limitations.
AB  - BACKGROUND: To evaluate the role of central and peripheral contributions to
      exercise limitation after transplantation, we compared, during exercise, 2 groups
      of very well-trained heart transplants recipients (HTRs) and kidney transplant
      recipients (KTRs) with a group of control subjects (CSs), matched for physical
      level. METHODS: Nineteen male subjects, 7 HTRs, 6 KTRs and 6 CSs, participated in
      the study. All transplant patients were in sinus rhythm and were matched for
      immunosuppressive therapy, none of whom had therapy with chronotropic effects.
      Exercise capacities were evaluated using a symptom-limited treadmill test. Oxygen
      consumption (VO2) and heart rate (HR) were measured continuously. Heart rate
      reserve (HRR) was defined as peak HR minus resting HR; resting HR was the
      stabilized HR measured in the supine position before the treadmill test. RESULTS:
      Functional capacities were evaluated for all HTRs, KTRs and CSs, according to
      maximal VO2 (41.5 +/- 4.0, 52.0 +/- 8.7 and 50.6 +/- 9.0 ml/kg per min,
      respectively), maximal treadmill speed (9.9 +/- 1.2, 12.7 +/- 1.9 and 15.5 +/-
      1.5 km/h) and HRR (65 +/- 17, 101 +/- 12 and 110 +/- 11 beats per minute [bpm]),
      which were significantly lower in the HTR group (p < 0.05). Regardless of type of
      organ transplant, both HTR and KTR patients had a similar VO2/treadmill speed
      relationship, significantly higher than in the CS group. HRR correlated with
      maximal VO2 for HTRs (r = 0.72, p < 0.05). CONCLUSIONS: Despite regular training,
      the decreased mechanical efficiency reflected by an increased VO2/treadmill speed
      relationship suggests a peripheral limitation in both heart and kidney transplant
      patients. Furthermore, exercise limitations in HTRs likely arose from both
      central and peripheral factors, in view of their specific HRR reduction. These
      factors probably contributed to the decreased speed and VO2 observed in the HTR
      group.

PMID- 16297782
TI  - Outcomes with an alternate list strategy for heart transplantation.
AB  - BACKGROUND: Heart transplantation (HT) is an effective therapy for end-stage
      heart failure, but its impact is limited by the scarcity of donor organs and
      stringent selection criteria for both donors and recipients. The creation of an
      alternate list to match recipients with contraindications to traditional HT with
      sub-optimal donor organs has been implemented at some centers, but outcomes using
      this approach are uncertain. METHODS: We created an alternate list that matched
      recipients in whom standard HT was contraindicated with donor organs that had
      been rejected for use in standard transplantation. Data on patient
      characteristics and outcomes were compared with a control group of patients
      transplanted on the standard list over the same time period. RESULTS: Fifty
      patients received HT on the alternate list, compared with 195 on the standard
      list. The most common reasons for recipient listing on the alternate list were
      age >65 years (n = 28) and diabetes with end-organ dysfunction (n = 9). Alternate
      list patients were older and more likely to have an ischemic etiology and
      diabetes mellitus. The most common reasons for allocation of donor organs to
      alternate-list patients were coronary artery disease (n = 12), positive hepatitis
      serology (n = 12) or left ventricular (LV) dysfunction (n = 8). Two-year survival
      was 70% for alternate-list patients compared with 88% for standard-list patients
      (p = 0.02). Post-transplant morbidity did not differ significantly between the 2
      groups except that alternate-list patients were hospitalized more frequently.
      CONCLUSIONS: The use of an alternate list can expand the applicability of HT to
      patients who would otherwise be denied this therapy. Although associated with
      greater morbidity and mortality than standard-list HT, alternate-list HT resulted
      in clinical outcomes that were significantly better than the natural history of
      end-stage heart failure.

PMID- 16297783
TI  - Freedom from graft vessel disease in heart and combined heart- and kidney
      transplanted patients treated with tacrolimus-based immunosuppression.
AB  - BACKGROUND: In end-stage cardiomyopathy where concomitant chronic renal failure
      is a contraindication for cardiac transplantation (HTx), simultaneous heart and
      kidney transplantation (HKTx) may be the only feasible therapeutic option. Due to
      the increased donor shortage, the clinical outcome of combined HKTx patients on
      tacrolimus-based immunosuppression was assessed and compared with a group of HTx
      patients. METHODS: Three hundred forty-nine HTxs, including 13 (4%) combined
      HKTxs, were performed since 1995. Two hundred twenty-one HTx and all HKTx
      recipients received tacrolimus-based immunosuppression. Acute rejection episodes
      (AREs), infections, renal function and clinical outcome were evaluated. Pre
      operative renal diagnoses for HKTx patients included cystic nephropathy (n = 4),
      glomerulonephritis (n = 4), cytostatica-induced nephropathy (n = 1), chronic
      rejection after renal transplant (n = 1), reflux nephropathy (n = 2) and chronic
      calcineurin-inhibitor -induced nephropathy after HTx (n = 1). Twelve patients
      (92%) were on hemodialysis pre-operatively, 1 underwent implantation of a left
      ventricular assist device (LVAD) before HKTx. RESULTS: After 4.7 +/- 2 years, 92%
      of HKTx compared with 85% of HTx patients had survived (p = 0.42). Acute cardiac
      rejection episodes were more frequent in HTx than in HKTx patients (0.04 +/- 0.09
      vs 0.02 +/- 0.04 ARE/100 patient-days; p = 0.07). Incidence of infection was
      comparable (0.3 +/- 0.2 vs 0.5 +/- 0.4 infection/100 patient-days). Freedom from
      transplant vasculopathy was 100% in the HKTx group compared with 71% in the HTx
      group after 4 years (p = 0.04). CONCLUSIONS: Tacrolimus-based immunosuppression
      yields promising long-term results in HKTx and HTx. The incidence of transplant
      vasculopathy seems to be lower after HKTx than after HTx. If these results are
      secondary to a protective effect of tacrolimus-induced tolerance or of tolerance
      associated co-transplantation they will need to be investigated in prospective
      multicenter trials.

PMID- 16297784
TI  - OKT3 treatment in refractory pediatric heart transplant rejection.
AB  - BACKGROUND: The anti-lymphocyte monoclonal antibody OKT3 has been shown to be
      effective in the management of steroid-resistant and/or fulminant heart
      transplant rejection in adults. In addition, some studies suggest that OKT3 may
      have a role in the management of transplant coronary artery disease (TxCAD). To
      date, there are limited data regarding the use of OKT3 treatment of refractory
      rejection or graft failure in children. Our study examines OKT3 treatment in
      steroid-resistant rejection, rejection with hemodynamic compromise, and TxCAD in
      children. METHODS: Thirty-eight patients received 53 courses of OKT3 for
      treatment of rejection and/or graft dysfunction. Primary indications for OKT3
      were steroid-resistant rejection (n = 27), rejection with hemodynamic compromise
      (n = 22), and TxCAD (n = 4). Resolution of rejection was considered absence of
      biopsy-proven rejection (< grade 2) or resolved TxCAD. RESULTS: OKT3 use in
      steroid-resistant rejection was associated with a lower incidence of rejection in
      the 3 months after OKT3 than 3 months before OKT3, median rejection episodes of
      2.5 vs 0, p < 0.0001. In rejection with hemodynamic compromise, 20 subjects (91%)
      demonstrated improved hemodynamics after OKT3 and survived to hospital discharge.
      The use of OKT3 treatment for TxCAD failed to demonstrate resolution or
      improvement in angiographic TxCAD in any subject. Only 5 OKT3 treatment courses
      were stopped secondary to severe adverse side effects. CONCLUSIONS: OKT3
      treatment in refractory pediatric heart transplant rejection is efficacious in
      acute rejection. OKT3 management in pediatric TxCAD is less clear, with no proven
      benefit identified in this study. OKT3 use in pediatric refractory heart
      rejection has significant side effects, but is tolerable and safe with close
      monitoring.

PMID- 16297785
TI  - Symptom complex is associated with transplant coronary artery disease and sudden
      death/resuscitated sudden death in pediatric heart transplant recipients.
AB  - BACKGROUND: Transplant coronary artery disease (TCAD) is a common sequela of
      heart transplantation. Symptom complexes associated with TCAD have not been well
      described. The purpose of this study was to determine if somatic complaints are
      associated with TCAD in pediatric heart transplant recipients. METHODS: We
      reviewed the medical records of all patients who underwent heart transplantation
      at our institution from November 1984 to December 2000. TCAD was defined as any
      interval narrowing of coronary arteries by angiography since the previous study
      or at least 50% luminal obstruction of 1 or more coronary arteries by histologic
      examination of explanted or autopsied hearts. RESULTS: Ninety-nine patients
      received heart transplants, and follow-up data were available in 80. Sixty-six
      patients met study criteria. Complaints of abdominal (82%), chest (45%),
      abdominal and chest (27%), and arm (9%) pain were made by 22 (33%) of 66
      patients, and TCAD was present in 27 (41%). Of the 22 patients with pain, TCAD
      was present in 18, for a positive predictive value of 82% (95% confidence
      interval [CI] 60%-95%). The relative risk of TCAD being present in patients with
      a history of pain was 4 times that of patients without pain (p < 0.001). Sudden
      death or resuscitated sudden death occurred in 15 (68%) of 22 patients with pain
      vs 4 (9%) of 44 without pain (p < 0.001). CONCLUSIONS: The symptom complex of
      abdominal, chest and/or arm pain is strongly associated with the presence of TCAD
      and sudden death or resuscitated sudden death in pediatric heart transplant
      recipients.

PMID- 16297786
TI  - Altered ventricular mechanics in cardiac allografts: a tissue Doppler study in 30
      children without prior rejection events.
AB  - BACKGROUND: Tissue Doppler imaging (TDI), a non-invasive echocardiography
      technique, permits quantitative analysis of the regional distribution pattern of
      myocardial velocities. During normal childhood development, regional function
      changes markedly, including an increasing predominance of longitudinal
      velocities. This study analyzed the impact of heart transplantation on
      ventricular mechanics in growing children. METHODS: TDI was performed in 30
      pediatric heart transplant recipients (7.1 +/- 6.2 years) and 32 age-matched
      healthy children (6.8 +/- 5.4 years). Patients had no rejection history and were
      3.1 years (median) post-transplant. Color TDI images from apical and parasternal
      views were stored as echocardiographic raw data. Off-line analysis was used to
      measure peak systolic and diastolic myocardial velocities in 6 basal cardiac
      segments for longitudinal (anterior, inferior, lateral, septal, right ventricle)
      and radial velocities (posterior). Isovolumic acceleration, a load-insensitive
      function marker, was determined as slope of the upstroke of the isovolumic
      contraction wave. Multiple regression modeling was used for statistics. RESULTS:
      Systolic myocardial velocities still increased with age after transplantation,
      but the velocity distribution pattern was changed. In transplanted hearts, left
      ventricular longitudinal velocities were lower and radial velocities were higher
      than in the controls, but isovolumic acceleration was similar. In the right
      ventricle, longitudinal velocities and isovolumic acceleration were significantly
      decreased after transplantation. Wall motion abnormalities were present in 50% of
      patients. CONCLUSIONS: Regional wall motion analysis shows significant
      alterations of the fundamental biomechanical pump function of the left ventricle
      after heart transplantation in children, with a shift from longitudinal to radial
      fibers and depressed right ventricular wall motion. This may have important
      implications for the long-term graft function required in children.

PMID- 16297788
TI  - Disruption of iron homeostasis in the lungs of transplant patients.
AB  - BACKGROUND: Oxidative stress has been proposed as a mechanism of injury
      underlying obliterative bronchiolitis. Catalytically reactive iron is a potential
      source of reactive oxygen species in transplanted tissue. Using samples acquired
      from surveillance bronchoalveolar lavage (BAL), we tested the postulate that
      there is a disruption of iron equilibrium in transplanted lung, which can worsen
      with time. METHODS: A control group of 5 healthy, non-smoking volunteers
      underwent BAL. Five bilateral lung transplant patients underwent surveillance BAL
      with transbronchial lung biopsies. The BAL fluid concentrations of protein,
      albumin, total iron, lactoferrin, ferritin, transferrin receptor and total iron
      binding capacity were measured. RESULTS: The mean ages in the control and
      transplant groups were 25.0 +/- 2.4 and 34.6 +/- 5.0 years, respectively.
      Patients were transplanted for cystic fibrosis (n = 3), primary ciliary
      dyskinesia (n = 1) and bronchiolitis obliterans (n = 1). Surveillance
      bronchoscopies were performed at 100.6 +/- 63.3, 175.0 +/- 87.7 and 259.2 +/- 82
      days post-transplant. No significant differences were noted in BAL protein,
      albumin and total iron binding capacity (TIBC) levels between the 2 groups. The
      BAL iron, transferrin, transferrin receptor, lactoferrin and ferritin levels were
      significantly elevated in transplant patients relative to controls. With time
      after transplantation, there were increases in lavage iron, transferrin receptor,
      lactoferrin and ferritin concentrations. CONCLUSIONS: Abnormally high levels of
      iron and its homeostatic proteins were found in the lung allografts, and levels
      appeared to increase with time. This supports a disruption in the normal
      homeostasis of this metal after transplantation and a potential role for a
      catalyzed oxidative stress in bronchiolitis obliterans. The use of iron-depleting
      therapy is a possible means for preventing injury in the lung allograft.

PMID- 16297787
TI  - High donor age, low donor oxygenation, and high recipient inotrope requirements
      predict early graft dysfunction in lung transplant recipients.
AB  - BACKGROUND: Early dysfunction in lung transplants is characterized by poor
      oxygenation, which may then lead to prolonged mechanical ventilation. This may be
      due to a combination of donor, recipient, and management factors. Our aim was to
      determine the incidence and severity of hypoxia and graft dysfunction and which
      factors were directly associated with poor oxygenation within the first 24 hours
      after lung transplantation. METHODS: A retrospective study of all 128 lung
      transplants between 1999 and 2002 was undertaken. Multiple linear regression
      analysis was performed to determine which donor, recipient, operative, and
      intensive care unit (ICU) parameters were associated with the worst recorded
      arterial blood gas partial pressure of oxygen (PAO2)/fraction of inspired oxygen
      (FIO2) ratio in the initial 24 hours after operation. RESULTS: Eighty-three
      percent of the patients (104 of 128) had a PAO2/FIO2 ratio below 300 within the
      first 24 hours post-transplantation, and 60% (77 of 128) had a PAO2/FIO2 ratio
      below 200. A high donor age (p = 0.004), low donor PAO2 (p = 0.007), and high
      post-operative inotrope requirements (p = 0.02) were correlated with a low
      PAO2/FIO2 ratio. Recipient diagnosis, ischemic time, use of cardiopulmonary
      bypass, fluid balance in the ICU, and cardiac index were not related. There was
      no difference in the long-term outcomes of patients with high or low PAO2/FIO2
      ratios. CONCLUSIONS: A low PAO2/FIO2 ratio is a common finding in the first 24
      hours after lung transplantation. Donor factors such as age and PAO2, and the
      need for increasing inotrope requirements in ICU predict early graft dysfunction
      and hypoxia.

PMID- 16297789
TI  - Multi-organ transplantation: is there a protective effect against acute and
      chronic rejection?
AB  - BACKGROUND: Heart-lung transplantation (Tx) is known to offer a protective effect
      against acute cardiac rejection. This study was undertaken to evaluate acute and
      chronic heart and/or lung rejection in the setting of multiple-transplanted
      organs from the same donor compared with single-organ transplantation. METHODS:
      Acute (treated rejection episodes of heart or lungs) and chronic (allograft
      vasculopathy in hearts and bronchiolitis obliterans syndrome [BOS] in lungs)
      rejection events were analyzed in 348 heart transplant (H) recipients, 24 heart
      lung (HL) recipients, 82 double-lung (L) recipients and 8 heart-kidney (HK)
      recipients >18 years of age, who were transplanted between 1990 and 2002.
      RESULTS: Survival at 3 years differed among groups as follows: HK, 100%; H, 82%;
      HL, 74%; and L, 70%. The probability of acute rejection within the first 3 months
      was higher in H recipients than in HL (81% vs 22%; p < 0.0001) or HK (81% vs 12%;
      p = 0.00009) recipients. Acute cardiac rejection occurred more frequently during
      the first 2 years in isolated H recipients compared with HL (2.8 vs 0.27
      episodes; p < 0.0001) and HK (2.8 vs 0.54; p < 0.001) recipients. Acute lung
      rejection occurred more frequently in the first 2 years in L than HL (2.4 vs 1.0
      episodes; p = 0.02) recipients. Chronic cardiac rejection (allograft
      vasculopathy) was more likely within 3 years after H compared with HL (32% vs
      16%; p = 0.04) or HK (32% vs 0%; p = 0.14). The onset of chronic lung rejection
      (BOS) within 3 years was similar in HL and L recipients (39% vs 40%; p = 0.9).
      CONCLUSIONS: Recipients of multiple organs from a single donor undergo less acute
      rejection of the heart or lungs compared with isolated heart or lung transplant
      recipients. Cardiac allograft vasculopathy is decreased significantly when
      cardiac transplantation is combined with a lung allograft. A lower incidence of
      cardiac allograft vasculopathy is observed when cardiac transplantation is
      combined with a renal allograft, and may prove statistically significant when
      more cases have been accumulated. These phenomena may result from immune
      modulation of the recipient by simultaneous transplant of disparate tissues or
      introduction of immune-modulating hematopoietic elements.

PMID- 16297790
TI  - The Copenhagen National Lung Transplant Group: survival after single lung, double
      lung, and heart-lung transplantation.
AB  - OBJECTIVE: To review the 13-year clinical experience of a single center's adult
      lung transplantation program. METHODS: From January 1992 to December 2003, 369
      lung transplantations were performed on 362 patients. Single lung transplantation
      was performed in 234 cases, double lung transplantation in 113 cases (comprising
      en-bloc double lung transplantation in 44 cases and bilateral sequential lung
      transplantation in 69 cases), heart-lung transplantation in 21 cases, and lobe of
      lung transplantation in 1 case. Recipient diagnoses included chronic obstructive
      pulmonary disease (COPD) (n = 175), alpha1 antitrypsin (alpha1AT) deficiency (n =
      86), cystic fibrosis (n = 36), pulmonary fibrosis (n = 20), Eisenmenger syndrome
      and secondary pulmonary hypertension (n = 24), primary pulmonary hypertension (n
      = 8), sarcoidosis (n = 7), silicosis (n = 4), bronchiectasis (n = 1), and graft
      vs-host disease (n = 1). RESULTS: For patients surviving to discharge, the median
      duration of the intensive care unit stay was 3 days (1-67), and the median
      duration of the post-operative hospital stay was 37 days (16-144). Mortality for
      the entire series was 6% at 30 days and 10% at 90 days. The main causes of post
      operative inpatient death were primary graft failure (41%), sepsis (29%), cardiac
      (15%), and hemorrhage (9%). The 1-, 3-, 5-, and 10-year actuarial survival rates
      for the entire series was 81%, 68%, 63%, and 36%, respectively. There were no
      significant differences in survival between types of transplant. No significant
      differences in survival were seen between alpha(1)AT deficiency and COPD patients
      after stratifying for age. Cox regression analysis demonstrated that age 60 years
      or older, donor age 50 years or older, and a recipient pre-operative body mass
      index of 25 or higher were independent predictors of poor survival. CONCLUSIONS:
      This center has 1-, 3-, and 5-year survival rates comparable to other high volume
      centers. Recipient age, pre-operative body mass index, and donor age
      significantly influence outcome after lung transplantation.

PMID- 16297791
TI  - FK778 and tacrolimus prevent the development of obliterative airway disease after
      heterotopic rat tracheal transplantation.
AB  - BACKGROUND: The effectiveness of the novel immunosuppressive agent FK778 and of
      tacrolimus to prevent the development of obliterative airway disease (OAD) was
      investigated in an animal model. METHODS: Tracheae from Brown-Norway donors were
      heterotopically transplanted in the greater omentum of Lewis rats. Recipients
      were treated for 28 days with FK778 (5 or 20 mg/kg), tacrolimus (1 or 4 mg/kg) or
      combination regimens at varying doses (5 + 1 mg/kg, 10 + 2 mg/kg or 20 + 4
      mg/kg). Grafts were harvested and processed for histologic and
      immunohistochemical evaluation. Lymphocyte surface antigen expression was
      quantified and in vitro smooth muscle cell (SMC) proliferation assays were
      performed. RESULTS: In untreated recipients, very large amounts of infiltrating
      CD4+, CD8+ and ED1+ mononuclear cells were observed in the peritracheal region
      with epithelial loss and complete luminal obliteration. Granulation tissue
      consisted of alpha-actin-positive cells and collagen-rich fibrosis. FK778 and
      tacrolimus as well as combination regimens of both agents dose-dependently
      inhibited peritracheal infiltration and luminal obliteration. Only tacrolimus
      treated recipients showed preserved luminal epithelial coverage with airway
      goblet cells, whereas, in animals that received FK778, no epithelium was found.
      Both agents equally suppressed in vivo lymphocyte CD25 expression. Only FK778
      treated animals were completely free of adverse drug side effects. FK778 but not
      tacrolimus showed potent anti-proliferative effects on SMC in vitro. CONCLUSIONS:
      Although both agents proved effective to prevent OAD development, histology
      revealed major differences. The anti-proliferative potency of FK778 on SMC may be
      an important mechanism of action. Combination regimens showed favorable drug
      interaction and allowed dose reduction of both agents to achieve maximal
      immunosuppressive efficacy.

PMID- 16297792
TI  - Prediction of cyclosporine blood levels in heart transplantation patients using a
      pharmacokinetic model identified by evolutionary algorithms.
AB  - BACKGROUND: Artificial intelligence (AI)-based computation methods have been
      recently shown to be applicable in several clinical diagnostic fields. The
      purpose of this study was to introduce a novel AI method called evolutionary
      algorithms (EAs) to clinical predictions. The technique was used to create a
      pharmacokinetic model for the prediction of whole blood levels of cyclosporine
      (CyA). METHODS: One hundred one adult cardiac transplant recipients were randomly
      selected and included in this study. All patients had been receiving oral
      cyclosporine twice daily, and the trough levels in whole blood were measured by
      monoclonal-specific radioimmunoassay. An evolutionary algorithm (EA)-based
      software tool was trained with pre- and post-operative variables from 64
      patients. The results of this process were then tested on data sets from 37
      patients. RESULTS: The mean value of the predicted CyA level throughout the
      measurement period for the test data was 175 +/- 27 ng/ml, which compared well
      with the mean observed CyA level of 180 +/- 31 ng/ml. The system bias expressed
      as the mean percent error (MPE) for the training and test data sets were 7.1 +/-
      5.4% (0.1% to 26.7%) and 8.0 +/- 6.7% (0.8% to 28.8%), respectively. The
      prediction accuracy ranged from 80% to 90%. The correlation coefficient between
      predicted and observed CyA concentration for the training data were 0.93 (p <
      0.001) and for the test data were 0.85 (p < 0.001), respectively. CONCLUSIONS:
      The results of this study suggest that the use of evolutionary algorithms to
      identify pharmacokinetic models yields accurate prediction of cyclosporine whole
      blood levels in heart transplant recipients. This and other similar technologies
      should be considered as future clinical tools to reduce costs in our health
      systems.

PMID- 16297793
TI  - Improvement of renal dysfunction by conversion from calcineurin inhibitors to
      sirolimus after heart transplantation.
AB  - BACKGROUND: Chronic renal dysfunction is a common occurrence after heart
      transplantation in patients treated with calcineurin inhibitors (CIs). We
      evaluated the renal-sparing effects of converting stable heart transplant
      patients with renal dysfunction from a CI to sirolimus. METHODS: Beginning in
      2000, heart transplant patients with renal dysfunction were converted from a CI
      to sirolimus. CI was abruptly discontinued and sirolimus added at 5 mg twice a
      day for 2 days and then 2 mg daily. The treatment goal was a 24-hour level of 6
      to 12 ng/ml. All patients were also managed with mycophenolate mofetil (MMF) at
      1,000 mg twice daily. RESULTS: Eighty from a total of 235 cardiac transplant
      patients were converted to sirolimus. The average time post-transplant for
      conversion was 4.78 years (range 3 days to 16 years). The average age at
      transplant was 55.43 years (range 15 to 70). At a mean of 304 days post
      conversion, the mean serum creatinine (sCr) decreased from 2.04 +/- 0.57 mg/dl
      pre-conversion to 1.64 +/- 0.48 mg/dl (p < 0.001). In patients whose sCr was <2.5
      mg/dl before conversion, the mean SCr level decreased from 1.81 +/- 0.39 to 1.62
      +/- 0.5 mg/dl post-conversion (p = 0.01), with no patient developing end-stage
      renal disease (ESRD). Four patients with sCr > or =2.5 developed ESRD requiring
      dialysis despite conversion. In the remaining 15 patients with sCr > or =2.5
      mg/dl, the sCr decreased from 2.85 +/- 0.29 to 1.73 +/- 0.43 mg/dl (p = 0.001).
      CONCLUSIONS: Conversion to sirolimus from CI is safe and has a renal-sparing
      effect in the management of heart transplant patients with chronic renal
      dysfunction. Based on these results, sirolimus has a role as a first-line
      immunosuppressive agent in heart transplant patients with renal dysfunction.

PMID- 16297794
TI  - Cyclosporine decreases vascular progenitor cell numbers after cardiac
      transplantation and attenuates progenitor cell growth in vitro.
AB  - OBJECTIVE: Recent experimental evidence suggests that the neointimal
      proliferation seen in cardiac allograft vasculopathy may in part derive from
      recipient progenitor cells. The effect of cyclosporine on these circulating
      progenitors in the setting of cardiac transplantation is currently unknown.
      METHODS: Three surgical series were performed: sham operation alone, sham
      operation with immunosuppression, and heterotopic porcine cardiac transplantation
      with immunosuppression. The sham operation involved laparotomy and consecutive
      clamping of the abdominal aorta and inferior vena cava. Post-operative
      immunosuppression consisted of cyclosporine at therapeutic levels (100-300 ng/ml)
      and 0.5 mg/kg methylprednisolone. Endothelial outgrowth colony numbers (EOC(CFU))
      and smooth muscle outgrowth colony numbers (SOC(CFU)) were quantified weekly for
      4 weeks post-operatively. A series of in vitro experiments were performed to
      determine the effect of cyclosporine on the differentiation, migration, and
      proliferation of EOCs and SOCs. RESULTS: In the sham alone series there were no
      changes to either EOC(CFU) or SOC(CFU). In the sham with immunosuppression and
      the transplant series, both EOC(CFU) and SOC(CFU) fell in the first 2 weeks (p <
      0.05) compared with baseline (EOC(CFU), 3.4 +/- 0.6; SOC(CFU), 11.1 +/- 2.8).
      EOC(CFU) recovered at 4 weeks to above baseline levels in the sham
      immunosuppression group only (15.2 +/- 3.9; p = 0.01). SOC(CFU) showed no
      recovery in the immunosuppression groups. Cyclosporine, even at a low dose,
      prevented differentiation, inhibited proliferation, and attenuated migration of
      both EOCs and SOCs. CONCLUSION: Immunosuppression in the setting of cardiac
      transplantation causes a profound reduction in circulating progenitor cells
      capable of differentiating into endothelial and smooth muscle cells. This effect
      can in part be explained by the inhibitory effects of cyclosporine on progenitor
      growth and differentiation seen in this study.

PMID- 16297795
TI  - Development of a reliable automatic speed control system for rotary blood pumps.
AB  - BACKGROUND: Axial blood pumps have been very successfully introduced into the
      arena of prolonged clinical support. However, they do not offer inherent load
      responsive mechanisms for adjusting pumping performance to venous return and
      changes in physiologic requirements of the patient. To provide for these
      adjustments we developed an algorithm for demand-responsive pump control based on
      a reliable suction detection system. METHODS: A PC-based system that analyzes
      pump performance based on available flow, heart rate and short-term performance
      history was developed. The physician defines levels of "desired flow" at rest and
      during exercise, depending on heart rate. In case this desired flow cannot be
      maintained due to limited venous return, the maximal available flow level is
      determined from an analysis of the actual pump data (flow, speed and power
      consumption). An expert system continuously checks the flow signal for any
      indication of suction. Periodic speed variations then adapt pump performance to
      the patient's condition. RESULTS: First, stability and functionality were proven
      under various settings in vitro. The algorithms were then tested in 15 patients
      in intensive care, in the standard ward, and during bicycle exercise. The system
      reacted properly to demand changes, at exercise level, in response to coughing
      and at various Valsalva maneuvers. Suction could also be successfully prevented
      during severe arrhythmia and in patients with critical cardiac geometry. Exercise
      tests showed decreases in pulmonary arterial pressure (-22 +/- 9.9%) and
      pulmonary capillary wedge pressure (-42 +/- 18.54%), and an increase in pump flow
      (19 +/- 9.5%) and workload (8 +/- 6.1%), all when compared with constant-speed
      pumping. CONCLUSIONS: A closed-loop control system equipped with an expert system
      for reliable suction detection was developed that improves response to change in
      venous return for rotary pump recipients. The system was robust, stable and safe
      under a wide range of everyday living conditions.

PMID- 16297796
TI  - Lack of sensitization and equivalent post-transplant outcomes with the Novacor
      left ventricular assist device.
AB  - BACKGROUND: Ventricular assist devices (VADs) are increasingly used to support
      critically ill heart failure patients awaiting transplantation. Previous work has
      focused on the Thoratec Heartmate VE device, use of which is associated with pre
      formed antibody production. We reviewed our cumulative experience with the
      Worldheart Novacor VAD as a bridge to transplantation (BTT). METHODS: From
      January 1989 through October 2002, 39 patients required a VAD bridge, with 26 of
      39 surviving to transplantation. Antibody levels were assessed by complement
      dependent cytotoxicity assay at routine intervals and expressed as panel reactive
      antibody (PRA) levels. Post-transplant allograft rejection, coronary
      vasculopathy, and survival were compared between Novacor-supported patients and
      non-VAD transplant recipients. RESULTS: PRA values did not significantly change
      after VAD implantation (12.4% +/- 11.2% vs 14.8% +/- 12.3%, p = 0.28). Survival
      for the BTT patients was 80.4%, 75.7%, 64.0%, 64.0%, and 64.0%, respectively, for
      1, 3, 5, 7, and 10 years post-transplant, with similar results for non-BTT
      patients. The freedom from coronary vasculopathy was 90.2%, 90.2%, 72.2%, and
      72.2%, respectively, at 1, 3, 5, and 7 years post-transplant. CONCLUSIONS: First,
      to our knowledge, this study is the first to examine the incidence of
      allosensitization after Novacor implant in detail. In contrast with previous
      results of work with other VAD systems, as assessed by PRA levels, Novacor
      patients did not become sensitized. Second, compared with 220 non-BTT patients
      who received transplants during a similar time frame, Novacor BTT patients had
      equivalent rejection profiles and survival. Finally, the incidence of transplant
      associated coronary artery disease was lower than in previous reports.

PMID- 16297797
TI  - Human metapneumovirus infection in lung transplant recipients: clinical
      presentation and epidemiology.
AB  - BACKGROUND: In immunocompromised patients, respiratory viruses are likely to lead
      to lower respiratory tract infections that cause severe morbidity and mortality.
      We conducted a prospective study from September 2003 to March 2004 to investigate
      the epidemiology and impact of human metapneumovirus (hMPV) on lung transplant
      recipients. METHODS: We collected 265 nasopharyngeal aspirates and
      bronchoalveolar lavages: 51 samples originated from immunocompromised adults, 49
      from lung transplant recipients, and 2 from a bone marrow recipient.
      Additionally, 209 samples from hospitalized non-immunocompromised children and 5
      samples from immunocompromised children were analyzed for replicating hMPV by a
      combined cell culture and reverse transcriptase polymerase chain reaction method
      that includes DNA sequencing of selected isolates. RESULTS: Twelve samples from
      lung transplant recipients (25%), 29 from non-immunocompromised children (14%),
      and 2 from a child with a renal transplant were positive for hMPV. Most of the
      cases clustered within 2 outbreaks in October/November and March. In
      immunocompromised patients, hMPV was isolated throughout the entire observation
      period. The same viral strains circulated in hospitalized children and in lung
      transplant recipients. A different strain was isolated during the interepidemic
      period, suggesting that hMPV infections may be transmitted among lung transplant
      recipients independently from the community outbreak situation. Clinical signs
      and symptoms varied from no symptoms to severe pneumonia or acute graft
      rejection. Significantly, the only deaths occurred in the hMPV-positive group. Of
      interest, identification of replicating hMPV significantly correlated with
      rejection symptoms present at the time point of sample collection. CONCLUSIONS:
      Results of the study suggest that hMPV may be added to the list of pathogens that
      are possibly associated with episodes of allograft rejection.

PMID- 16297798
TI  - The intensive care unit oxygen challenge should not be used for donor lung
      function decision-making.
AB  - BACKGROUND: The intensive care unit oxygen challenge is a routine screening test
      for donor lung function. An arterial PO2 of <300 mm Hg is generally considered
      evidence of inadequate pulmonary function that contraindicates the use of the
      lungs for transplantation. METHODS: Between December 1, 2001 and January 24,
      2004, the intensive care unit oxygen challenge was compared with the PO2 in
      samples drawn from each pulmonary vein confluence in the operating room in 91
      donors (182 donor lungs) after the lungs were fully inflated (FIO2 1.0). There
      were 62 males and 29 females, with a median age of 27.5 years (13.6 to 55.4
      years). RESULTS: In 40 lungs, the pulmonary vein PO2 was >300 mm Hg, whereas the
      PO2 was <300 mm Hg on the last intensive care unit O2 challenge. The difference
      between the intensive care unit PO2 and the operating room pulmonary vein PO2 was
      greatest for donors with the lowest intensive care unit PO2. Of these 40 lungs, 8
      were transplanted, all of whom had excellent graft function with a median
      intubation of 14.2 hours (6.1 to 23.8 hours). No patient sustained primary graft
      failure or an airway complication. CONCLUSIONS: The intensive care unit PO2 is an
      unreliable screening test for donor lung function, particularly when one lung is
      clear and the other is unclear radiographically. In this setting, intraoperative
      surgical assessment and pulmonary venous PO2 should be the basis for determining
      donor lung suitability. This strategy may provide an opportunity to increase
      donor lung availability.

PMID- 16297799
TI  - Prolonged cold ischemia in rat cardiac allografts promotes ischemia-reperfusion
      injury and the development of graft coronary artery disease in a linear fashion.
AB  - BACKGROUND: Prolonged cold ischemia is thought to exacerbate ischemia-reperfusion
      injury and graft coronary artery disease (GCAD). We investigated the effect of
      varying lengths of cold ischemia on inflammation and apoptosis during ischemia
      reperfusion injury and correlated this with the degree of GCAD in rat cardiac
      allografts. METHODS: PVG rat (RT1c) hearts subjected to 30, 60, 90, 120, or 150
      minutes of cold ischemia were heterotopically transplanted into ACI rats (RT1a).
      Grafts were procured after 4 hours of reperfusion and analyzed for superoxide
      generation, myeloperoxidase activity, tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), and monocyte chemoattractant protein-1/chemokine (C
      C motif) ligand 2 (MCP-1/CCL2) production, cardiomyocyte apoptosis, and caspase
      2, -3, -8, -9 activities. Additional transplanted animals received cyclosporine A
      (7.5 mg/kg/day) for 10 days as chronic rejection models. Indices of GCAD were
      determined at 90 days. RESULTS: A direct linear correlation was found between
      cold ischemic time, ischemia-reperfusion injury, and GCAD. Superoxide generation,
      myeloperoxidase activity, TNF-alpha, IL-1beta, MCP-1/CCL2 production,
      cardiomyocyte apoptosis, and caspase-2, -3, -8, and -9 activities increased with
      ischemic time, peaking at 120 minutes and plateauing at 150 minutes. GCAD,
      assessed by the percentage of luminal narrowing, the intima/media ratio, and the
      percentage of diseased vessels, worsened with increased ischemic time, peaking at
      120 minutes and plateauing at 150 minutes. All tested variables in both the acute
      and chronic phases were significantly increased with 120-minute ischemia compared
      with 30-minute ischemia. CONCLUSIONS: These data indicate that the degree of
      cardiomyocyte apoptosis and inflammatory response in cardiac allografts during
      ischemia-reperfusion injury depends on the duration of cold ischemia. More
      important, that prolonged cold ischemia correlates with increased GCAD.

PMID- 16297800
TI  - Improved viability and reduced apoptosis in sub-zero 21-hour preservation of
      transplanted rat hearts using anti-freeze proteins.
AB  - BACKGROUND: Freeze-tolerant fish survive sub-zero temperatures by non
      colligatively lowering the freezing temperature of their body fluids using anti
      freeze proteins (AFPs). We sought to evaluate and compare the effects of
      prolonged sub-zero cryopreservation of transplanted rat hearts using AFP I or AFP
      III. METHODS: Two heterotopic rat heart transplantation protocols were used. In
      Protocol 1 (n = 104), hearts (n = 8/group) were preserved for 12, 18 and 24 hours
      in University of Wisconsin solution (UW) at 4 degrees C, UW at -1.3 degrees C,
      UW/AFP I at -1.3 degrees C and UW/AFP III at -1.3 degrees C, with and without
      nucleation. Post-operative evaluation consisted of visual viability scoring of
      the hearts after 60 minutes. Protocol 2 (n = 58) involved evaluation of 24-hour
      post-transplant viability, echocardiography (fractional shortening [FS], left
      ventricular end-systolic and -diastolic diameter [ESD, EDD] and anterior and
      posterior wall systolic and diastolic thickness [AWT-S, AWT-D, PWT-S, PWT-D]),
      TUNEL staining and electron microscopy (EM) findings for hearts preserved for 18,
      21 and 24 hours in UW at 4 degrees C or UW/AFP III at -1.3 degrees C. RESULTS:
      Hearts preserved in UW at -1.3 degrees C with nucleation froze and died. Three of
      8 hearts preserved in UW at 4 degrees C for 24 hours died, whereas all hearts
      preserved at -1.3 degrees C survived. Hearts preserved in UW/AFP for 18 and 24
      hours at -1.3 degrees C had superior viability scores compared with those in UW
      at 4 degrees C. Hearts in AFP III at -1.3 degrees C displayed greater AWT-S and
      AWT-D (3.5 +/- 0.2 vs 2.4 +/- 0.2, p < 0.05, and 3.5 +/- 0.2 vs 2.2 +/- 0.2, p <
      0.05, respectively) after 18-hour preservation. In the 21-hour preservation
      group, AFP-treated hearts displayed improved echocardiographic systolic
      contraction indices, including: improved FS (27 +/- 3.7 vs 15 +/- 4, p = 0.04);
      diminished ESD (0.28 +/- 0.57 vs 0.47 +/- 0.6, p < 0.05); greater AWT-S (3.4 +/-
      0.18 vs 2.8 +/- 0.2, p < 0.05); and fewer positively TUNEL-stained nuclei per
      specimen (35 +/- 14 vs 5.3 +/- 2.7, p = 0.04). Also, improved EM scores were
      noted compared with UW at 4 degrees C. CONCLUSIONS: In prolonged sub-zero
      cryopreservation, AFPs protect the heart from freezing, improve survival and
      hemodynamics, and reduce apoptotic cell death.

PMID- 16297801
TI  - Stem-like cells traffic from heart ex vivo, expand in vitro, and can be
      transplanted in vivo.
AB  - BACKGROUND: Cells with stem cell surface markers have been identified in heart
      tissue. Early indications suggest that these are cardiac progenitor cells that
      could contribute to cardiac repair/regeneration. Clinically relevant therapeutic
      strategies based on these cells will require improved methods for their isolation
      and characterization of determinants of their mobilization, proliferation and
      differentiation. METHODS: An ex vivo culture system was developed that promotes
      trafficking of progenitor-like cells from mouse ventricles to a culture surface.
      Cells that "trafficked" from cardiac tissue were phenotyped by flow cytometry and
      immunohistochemistry. RESULTS: Morphologically distinct cells spontaneously
      trafficked from mouse ventricular tissue, adhered in culture, and proliferated
      for up to 4 weeks in Dulbecco's minimal essential media supplemented with fetal
      calf serum. After 4 weeks in culture, cell number declined. Co-culture with
      unfractionated bone marrow restored the proliferation of these trafficked cells.
      A significant population of the trafficked cells expressed a phenotype consistent
      with that of a myogenic progenitor such as: c-kit+, Sca-1+, CD45-, CD34-, CD90.2
      , MyoD1-, desmin-, muscle-specific actin-, and, infrequently, myogenin+. An
      expanded population of trafficked cells from ventricles of mice expressing green
      fluorescent protein (GFP+) and containing cardiac-derived progenitor cells were
      injected into the pericardial space of GFP- mice. GFP+ cells trafficked
      throughout the heart but retained a primitive undifferentiated morphology.
      However, when injected into the pericardial space of Apo-E-deficient mice with
      coronary vasculopathy, progenitor-like cells trafficked into myocardium, and GFP+
      cells differentiated into vessel-lining endothelial cells and, rarely, smooth
      muscle and cardiomyocytes. CONCLUSIONS: Progenitor-like cells in the heart can be
      mobilized by tissue injury to spontaneously traffic from cardiac tissue and can
      expand in culture by co-culture with bone marrow. When re-infused by
      pericardiocentesis, these primitive cells traffic into heart, retain immature
      morphology, but are capable of undergoing injury-induced differentiation. The
      novel method described herein permits further characterization of cardiac-derived
      progenitor cells, which are a candidate for cardiac regeneration strategies.

PMID- 16297802
TI  - Autologous skeletal myoblast transplantation improved hemodynamics and left
      ventricular function in chronic heart failure dogs.
AB  - BACKGROUND: Previous studies have suggested that autologous skeletal myoblast
      transplantation (ASMT) improves left ventricular (LV) function in small animals
      after myocardial infarction. We tested the effects of ASMT on hemodynamics, LV
      function and remodeling in coronary microembolization-induced chronic heart
      failure (CHF) in conscious dogs. METHODS: Nineteen dogs were continuously
      instrumented with LV pressure sensors and mid-myocardial sonomicrometry crystals
      for dP/dt(max) and LV volume determination. Each dog underwent baseline
      assessment in a conscious state. CHF (20% to 30% reduction in dP/dt(max) and LV
      end-diastolic pressure >16 mm Hg) was created by daily coronary
      microembolizations via a continuously implanted coronary catheter. Skeletal
      muscle biopsy was performed and myoblasts were isolated and expanded. Then 2.7 x
      10(8) to 8.3 x 10(8) myoblasts were injected into the infarcted region of 11 dogs
      after establishment of CHF. Saline injection (sham) was performed in 8 control
      dogs. Animals were evaluated every 2 weeks for up to 10 weeks. Global ejection
      fraction was determined by echocardiography. The end-systolic pressure-end
      systolic volume relationship (ESPVR) was analyzed by the Sonomicrometic system.
      RESULTS: Compared with saline injection, ASMT significantly increased dP/dt(max)
      (105 +/- 9% vs 97 +/- 7%, values were expressed as percentage change from
      baseline CHF, p = 0.013) and ejection fraction (46 +/- 3% vs 40 +/- 2%, p =
      0.034) at 10 weeks after myoblast transplantation. There was a significant
      leftward and upward shift of the ESPVR back toward normal at 10 weeks after
      myoblast transplantation (p = 0.034). Three animals labeled with BrdU myoblasts
      showed no histologic evidence of viable engraftment. CONCLUSIONS: ASMT provided
      mild improvements in hemodynamics and LV function and reduced LV remodeling in
      conscious dogs with CHF.

PMID- 16297803
TI  - Combined administration of intravenous dipyridamole and inhaled nitric oxide to
      assess reversibility of pulmonary arterial hypertension in potential cardiac
      transplant recipients.
AB  - BACKGROUND: Irreversible, severe pulmonary hypertension (PH) can produce right
      heart failure and early mortality after cardiac transplantation. We hypothesized
      that dipyridamole, an inhibitor of Type 5 phosphodiesterase, would augment the
      ability of inhaled nitric oxide (NO) to identify reversibility of PH. METHODS: In
      9 patients with congestive heart failure (CHF) and severe PH who were breathing
      100% oxygen during right heart catheterization, we administered inhaled NO (80
      ppm) alone and in combination with intravenous dipyridamole (0.2-mg/kg bolus,
      with an infusion of 0.0375 mg/kg/min). RESULTS: Compared with breathing oxygen
      alone, NO inhalation decreased pulmonary artery pressure and pulmonary vascular
      resistance (PVR) (by 10 +/- 4% and 26 +/- 12% [mean +/- SEM], respectively; both
      p < 0.05). The combination of NO and dipyridamole reduced PVR (43 +/- 7%; p <
      0.05) to a greater extent than did administration of NO alone, and increased the
      duration of pulmonary vasodilation produced by NO inhalation. Combined
      administration of inhaled NO and intravenous dipyridamole increased cardiac index
      (by 23 +/- 10%) and reduced SVR (by 19 +/- 6%, both p < 0.05) without changing
      systemic arterial pressure. NO inhalation reduced PVR to <200 dyne x s/cm5 in 3
      of 7 patients who had a PVR of >200 dyne x s/cm5 when breathing oxygen alone,
      whereas the combination of NO and dipyridamole decreased PVR to <200 dyne.s/cm(5)
      in 2 additional patients. CONCLUSIONS: Intravenous dipyridamole augments and
      prolongs the pulmonary vasodilator effects of inhaled NO in CHF patients with
      severe PH and, when administered in combination with NO inhalation, can identify
      PH reversibility in potential cardiac transplant recipients in whom a pulmonary
      vasodilator response to inhalation of NO alone is not observed.

PMID- 16297804
TI  - Partial left ventriculectomy and mitral valve repair: favorable short-term
      results in carefully selected patients with advanced heart failure due to dilated
      cardiomyopathy.
AB  - BACKGROUND: Because of the scarcity of donor hearts, surgical alternatives to
      heart transplantation, such as partial left ventriculectomy (PLV), were
      introduced for treatment of advanced heart failure. Here, we report our
      experience with this procedure performed in combination with mitral valve repair.
      METHODS: Twelve patients with dilated cardiomyopathy (DCM), New York Heart
      Association (NYHA) class exceeding III on maximal medical therapy, cardiac index
      of 2.5 liter/min/m2 or less, VO2max of 14 ml/kg/min or less, left ventricular end
      diastolic diameter (LVEDD) of 7.0 cm or more, and grade II or greater mitral
      incompetence, were selected for PLV and mitral valve reconstruction (MVR).
      Echocardiography, hemodynamics, spiroergometry, and clinical assessment were
      performed before and 1 year after the operation. RESULTS: One-year survival was
      83.3%. All 10 surviving patients were free from failure of the procedure 1 year
      post-operatively. From pre-operatively to 1 year post-operatively, NYHA
      functional class improved from 3.3 +/- 0.3 to 1.9 +/- 0.2 (p < 0.001), cardiac
      index increased from 2.0 +/- 0.2 liter/min/m2 to 2.9 +/- 0.2 liter/min/m2 (p <
      0.001), stroke volume index from 25.9 +/- 4.8 ml/m2 to 40.3 +/- 7.3 ml/m2 (p =
      0.008), and VO2max from 10.9 +/- 2.4 ml/kg/min to 16.0 +/- 3.6 ml/kg/min (p =
      0.016), whereas LVEDD decreased from 8.4 +/- 0.6 cm to 6.6 +/- 0.3 cm (p <
      0.001), left ventricular end-systolic diameter from 6.8 +/- 0.8 cm to 5.3 +/- 0.5
      cm (p < 0.001), and mitral incompetence from 2.4 +/- 0.6 to 0.9 +/- 0.6 (p <
      0.001). Pulmonary pressures and fractional shortening did not change
      significantly (p > 0.05). Four patients received an implantable
      cardioverter/defibrillator as a result of their pathologic electrophysiologic
      examination. CONCLUSIONS: In carefully selected patients, PLV combined with MVR
      achieves short-term results comparable to that after heart transplantation.
      However, long-term results and multicenter evaluation will be needed to define
      its place in the treatment of advanced heart failure.

PMID- 16297805
TI  - The need for a tailored immunosuppression in older heart transplant recipients.
AB  - Advanced recipient age is considered a relative contraindication for heart
      transplantation because it might be associated with increased morbidity and
      mortality. We analyzed 349 consecutive heart transplantations performed at our
      institution from 1995 to 2002 (n = 349, mean follow-up 3.5 +/- 2.5 years). The
      survival rate was lower in older recipients. Less chronic rejection but increased
      risk for infectious complications, renal failure and neoplasms indicate the need
      for decreased immunosuppression and effective infection prophylaxis in older
      recipients.

PMID- 16297806
TI  - Effects of conversion from cyclosporine to tacrolimus on left ventricular
      structure in cardiac allograft recipients.
AB  - Twelve heart transplant recipients selected for conversion from cyclosporine to
      tacrolimus because of adverse effects of cyclosporine therapy underwent
      echocardiography at baseline and 6 months after conversion. Left ventricular mass
      decreased by 24% and left ventricular geometry returned toward normal at 6 months
      after conversion, without significant changes in blood pressure.

PMID- 16297807
TI  - Comparison of Novacor and HeartMate vented electric left ventricular assist
      devices in a single institution.
AB  - We compared the survival outcomes, left ventricular assist device (LVAD)-related
      hospitalization, stroke, infection, panel reactive antibody, and blood product
      use data among 13 Novacor and 51 HeartMate system recipients. Stroke was
      significantly higher in Novacor patients, as was blood product use at the time of
      heart transplantation, likely due to long-term anti-coagulation, while the LVAD
      related hospitalization and infections did not differ between the 2 groups. A
      positive panel reactive antibody was seen more among the HeartMate patients, but
      did not have a significant clinical impact and may not represent a true
      allosensitization.

PMID- 16297808
TI  - Reduced myocardial blood flow during left ventricular assist device support: a
      possible cause of premature bypass graft closure.
AB  - Our aim was to determine the effect of left ventricular assist device (LVAD)
      implantation on bypass graft patency and to measure myocardial oxygen consumption
      (MVO2) and blood flow during LVAD support. Five patients who underwent coronary
      artery bypass grafting and required LVAD implantation for post-cardiotomy
      cardiogenic shock had coronary angiography during device support to assess graft
      patency. Positron emission tomography measurements were made in a separate cohort
      of LVAD patients with dilated cardiomyopathy to assess the effects of LVAD
      support on MVO2 and myocardial blood flow. In this small series, LVAD unloading
      led to a high rate of premature graft occlusion in post-cardiotomy cardiogenic
      shock patients supported with a device; whereas, positron emission tomography
      measurements showed significantly reduced MVO2 and myocardial flood flow in
      dilated cardiomyopathy patients supported with an LVAD, compared with healthy
      subjects. Reduced myocardial blood flow may be implicated in the premature graft
      failure observed in post-cardiotomy cardiogenic shock patients and may negatively
      impact the potential for myocardial recovery and device weaning in this
      population.

PMID- 16297809
TI  - Fatal stongyloides hyperinfection in heart transplantation.
AB  - S stercoralis is an intestinal parasite that normally causes a chronic, low
      grade, mostly asymptomatic infection. Hyperinfection syndrome and dissemination,
      with secondary sepsis, may occur in immunosuppressed patients, especially those
      on corticosteroid therapy. We present a case of fatal strongyloidiasis occurring
      in a patient 1 month after orthotopic heart transplantation (OHT). We assess the
      diagnostic challenges in these patients where pulmonary and gastrointestinal
      symptoms predominate as presenting clinical manifestations. We also investigate
      the role of screening and prophylactic anti-helmintic therapy in patients at high
      risk of harboring the occult intestinal infection.

PMID- 16297810
TI  - Multiple peripheral pulmonary artery stenoses in adults: a rare cause of severe
      pulmonary hypertension necessitating lung transplantation.
AB  - Stenoses of multiple peripheral pulmonary artery branches represent a rare cause
      of pulmonary hypertension in children, but the prognosis is very poor for such
      patients. Herein we describe 2 patients with multiple peripheral pulmonary artery
      stenoses (MPPAS) presenting with severe pulmonary arterial hypertension in
      adulthood, which has only once been described previously. Both patients lived
      without significant health problems for decades; however, after onset of
      symptoms, their medical condition declined rapidly, necessitating lung
      transplantation several months after the diagnosis despite vasodilator therapy.
      Because MPPAS mimics chronic thromboembolic pulmonary hypertension, this entity
      may being underdiagnosed, decreasing the possibility of adequate therapy.

PMID- 16297811
TI  - Recurrence of cardiac sarcoidosis in a heart transplant recipient.
AB  - We present the case of a young man who received a left ventricular assist device
      (LVAD) as a bridge to transplantation for end-stage heart failure, in whom the
      diagnosis of sarcoid cardiomyopathy was made at the time of LVAD implantation. He
      subsequently underwent uncomplicated heart transplantation. Nineteen months
      later, a routine surveillance endomyocardial biopsy specimen demonstrated
      recurrence of sarcoidosis in the transplanted heart.

PMID- 16297812
TI  - Mediastinal mass due to Aspergillus fumigatus after lung transplantation: a case
      report.
AB  - We report a rare case of mediastinal mass caused by Aspergillus fumigatus in a
      lung transplant recipient. The patient presented 9 months after bilateral lung
      transplantation for cystic fibrosis with intermittent fevers and new onset atrial
      fibrillation/flutter caused by a 7-cm mediastinal mass invading the left atrium.
      The mass was resected, and a prolonged course of voriconazole and caspofungin was
      given, which resulted in a complete clinical response. Despite long-term
      suppressive therapy with voriconazole, a relapse occurred 16 months after the
      initial diagnosis. This case highlights the challenges in the prevention and
      treatment of invasive aspergillosis in lung transplant recipients.

PMID- 16297813
TI  - Myocardial protection of the donor heart and the avoidance of oxidative stress.

PMID- 16297814
TI  - Role of pharmacologically mobilized endogenous bone marrow stem cells for cardiac
      repair.

PMID- 16297815
TI  - Heart transplant and left ventricular assist device costs.

PMID- 16297816
TI  - Reversible pulmonary hypertension in heart transplant candidates does not
      obligatorily predict worse outcome post-transplantation.

PMID- 16297817
TI  - Heart allograft lymphatic system changes and Quilty lesion.

PMID- 16297818
TI  - Donor-recipient gender mismatch in lung transplantation: Impact on obliterative
      bronchiolitis and survival.

PMID- 16297821
TI  - Pulsed low-intensity ultrasound for fracture healing.
AB  - A large body of evidence confirms the stimulatory effect of pulsed low-intensity
      ultrasound on fresh fractures, nonunions, and other osseous defects such as
      osteotomies. This article presents the findings of some of these studies and
      briefly discusses our current understanding of its molecular mechanisms.

PMID- 16297822
TI  - Electrical bone stimulation: an overview and its use in high risk and Charcot
      foot and ankle reconstructions.
AB  - Since early work done in the 1950s on the "piezoelectricity of bone," a growing
      body of basic science and clinical evidence suggests the use of electrical bone
      stimulation as an adjunct in the treatment of foot and ankle nonunions, fusions,
      and Charcot arthropathy. Both implantable designs (that allow for direct constant
      stimulation of bone) and nonimplantable (such as pulsed and combined
      electromagnetic fields) devices have been studied. Ongoing research continues to
      support the potential usefulness of these modalities.

PMID- 16297820
TI  - The role of electrical stimulation in bone repair.
AB  - Electric and electromagnetic fields regulate extra-cellular matrix synthesis and
      stimulate repair of fractures and nonunions. Studies of electric and
      electromagnetic fields suggest they (1) regulate proteoglycan and collagen
      synthesis and increase bone formation in models of endochondral ossification, (2)
      accelerate bone formation and repair, (3) increase union rates in fractures
      previously refractory to healing, and (4) produce results equivalent to bone
      grafts. Electric and electromagnetic fields regulate the expression of genes in
      connective tissue cells for extra-cellular matrix proteins, which results in an
      increase in cartilage and bone. They also increase gene expression for and
      synthesis of growth factors, which may be an intermediary mechanism of activity
      and may amplify field effects through autocrine and paracrine signaling.

PMID- 16297823
TI  - The role of platelet-rich plasma in foot and ankle surgery.
AB  - Platelet-rich plasma (PRP), derived from autologous blood, is defined as a volume
      of plasma that has a platelet concentration that typically is five times greater
      (approximately 1,000,000/microl) than physiologic levels. PRP serves as a
      reservoir of critical growth factors, including platelet-derived growth factor,
      transforming growth factor-beta, and insulin-like growth factor-I. Although there
      is an abundance of literature pertaining to dental applications, this article
      highlights the use of PRP in orthopedic applications, ranging from PRP
      preparation to in vitro and in vivo studies to clinical research.

PMID- 16297824
TI  - Recombinant human bone morphogenetic proteins in the treatment of fractures.
AB  - Recently, several prospective randomized clinical trials have resulted in the
      publication of critical studies on the efficacy of recombinant human
      morphogenetic proteins BMP-2 (rhBMP-2) and BMP-7 (OP-1) in spinal fusion and
      fracture healing. The clinical use of BMPs is now in its infancy and
      understanding the mechanism and the appropriate application of these proteins is
      necessary for all practicing orthopedic surgeons. This article will revisit some
      of the early studies using rhBMPs and review the current literature on their role
      in fracture healing.

PMID- 16297825
TI  - Mesenchymal stem cells for bone repair: preclinical studies and potential
      orthopedic applications.
AB  - Mesenchymal stem cells (MSCs), derived from adult bone marrow, are multi-potent
      stem cells capable of differentiating along several lineage pathways. From a
      small bone marrow aspirate, MSCs can be readily isolated and easily expanded.
      Therefore, MSCs are thought to be a readily available source of cells for many
      tissue engineering and regenerative medicine applications. This review covers
      preclinical models that evaluate the efficacy of MSC-loaded scaffolds in large
      bone defects as a potential substitute for autologous and allogeneic bone grafts.
      This review also covers new approaches to clinical use of MSC technology.

PMID- 16297826
TI  - Bioabsorbable fixation in foot and ankle.
AB  - Bioabsorbable implants are playing an increasing role in the surgical management
      of foot and ankle pathologies. Current technology allows implants to have
      acceptably comparable strength and pull-out characteristics to metallic implants.
      The advantages include elimination of secondary surgeries, biodegradability of
      implants placed across mobile articular surfaces, as well as acceptable
      biocompatibility and resorption properties to limit historical complication
      concerns.

PMID- 16297827
TI  - Ankle joint distraction.
AB  - Ankle joint distraction is a viable alternative to ankle arthrodesis or ankle
      replacement. A congruent, painful, mobile, and arthritic ankle joint that is
      treated with this technique can achieve good to excellent results. Attention to
      the principles (anterior osteophyte resection, equinus contracture release, and
      ankle joint realignment procedures) is as important for a successful outcome as
      the accurate application of the hinged ankle joint distraction technique itself.

PMID- 16297828
TI  - The role of extracorporeal shock wave on plantar fasciitis.
AB  - Extracorporeal shock wave therapy for chronic plantar fasciitis has been under
      investigation since its advent in the early 1990s. Its use has been approved by
      the U.S. Food and Drug Administration; however, much controversy exists
      surrounding its mechanism of action, treatment protocols, and clinical efficacy.
      This article reviews some of the existing theories, opinions, and data in an
      attempt to summarize the current role that shock wave therapy plays in the
      treatment of plantar fasciitis.

PMID- 16297829
TI  - Contemporary approaches to stage II and III hallux rigidus: the role of metallic
      hemiarthroplasty of the proximal phalanx.
AB  - Metallic proximal phalangeal hemiarthroplasty has been described for the surgical
      treatment of moderate to severe hallux rigidus. This long-term follow-up of an
      extended case series of 37 patients who underwent the index operation
      demonstrated a high rate (93%) of patient satisfaction, and significant
      improvement in Foot Function Index scores.

PMID- 16297830
TI  - The role of cyclooxygenase-2 inhibition in foot and ankle arthrodesis.
AB  - Cyclooxygenase-2 (COX-2) inhibitors are an important adjunct in controlling
      postoperative pain. Concerns exist regarding the use of NSAIDs for postoperative
      pain management because of the possible deleterious impact on bone healing in
      patients undergoing hindfoot arthrodesis. Orthopedic surgeons are concerned with:
      (1) a multimodal approach for postoperative pain control, and (2) bone healing
      following arthrodesis, fracture repair with rigid internal fixation, and
      cementless implants. The use of COX-2 inhibitors has been shown to be an
      important component of a pain control strategy but questions about their effects
      on bone healing have inhibited their use. This article discusses the laboratory
      and clinical data available on the use of COX-2 inhibitors on bone healing and
      their effects on foot and ankle arthrodesis procedures.

PMID- 16297831
TI  - The hard way to a Bill of Rights.

PMID- 16297832
TI  - Study of prion types questions classification system.

PMID- 16297833
TI  - Quantifying consciousness.

PMID- 16297834
TI  - ISAT: coiling or clipping for ruptured intracranial aneurysms?

PMID- 16297835
TI  - The hippocampus and remote autobiographical memory.

PMID- 16297836
TI  - Birth order, infection in early life, and multiple sclerosis.

PMID- 16297838
TI  - Coexistence of multiple PrPSc types in individuals with Creutzfeldt-Jakob
      disease.
AB  - BACKGROUND: The molecular typing of sporadic Creutzfeldt-Jakob disease (CJD) is
      based on the size and glycoform ratio of protease-resistant prion protein
      (PrP(Sc)), and on PRNP haplotype. On digestion with proteinase K, type 1 and type
      2 PrP(Sc) display unglycosylated core fragments of 21 kDa and 19 kDa, resulting
      from cleavage around amino acids 82 and 97, respectively. METHODS: We generated
      anti-PrP monoclonal antibodies to epitopes immediately preceding the differential
      proteinase K cleavage sites. These antibodies, which were designated POM2 and
      POM12, recognise type 1, but not type 2, PrP(Sc). FINDINGS: We studied 114 brain
      samples from 70 patients with sporadic CJD and three patients with variant CJD.
      Every patient classified as CJD type 2, and all variant CJD patients, showed
      POM2/POM12 reactivity in the cerebellum and other PrP(Sc)-rich brain areas, with
      a typical PrP(Sc) type 1 migration pattern. INTERPRETATION: The regular
      coexistence of multiple PrP(Sc) types in patients with CJD casts doubts on the
      validity of electrophoretic PrP(Sc) mobilities as surrogates for prion strains,
      and questions the rational basis of current CJD classifications.

PMID- 16297839
TI  - Prevalence of movement disorders in men and women aged 50-89 years (Bruneck Study
      cohort): a population-based study.
AB  - BACKGROUND: There is emerging awareness that movement disorders rank among the
      most common neurological diseases. However, the overall burden of these disorders
      in the general community is not well defined. We sought to assess the prevalence
      of all common categories of movement disorders in a population, accounting for
      sex differences and age trends. METHODS: As part of an ongoing prospective
      population-based study of carotid atherosclerosis and stroke risk (the Bruneck
      Study), a total of 706 men and women aged 50-89 years underwent a thorough
      neurological assessment. The diagnosis of movement disorders and ratings for
      disease severity were based on standard criteria and scales. Prevalences were
      estimated from logistic regression models (regression-smoothed rates) and
      standardised to the age and sex structure of the general community. FINDINGS: The
      prevalence of all common categories of movement disorders was 28.0% (95% CI 25.9
      30.1). Proportions in men (27.6% [95% CI 24.5-30.7]) and women (28.3% [25.5
      31.2]) were closely similar and sharply increased with age (from 18.5% [15.0
      22.0] in 50-59-year olds to 51.3% [44.9-57.7] in 80-89-year olds). Almost half of
      all patients (90/214) had moderate-to-severe disease expression, but only 7.0%
      (15/214) received standard drug treatment. Prevalence of tremor was 14.5%,
      followed by restless legs syndrome (10.8%), parkinsonism (7%), primary dystonia
      and secondary dystonia (1.8%), and chorea and tics (<1% each). A fifth of all
      movement disorders were diagnosed to be probably drug-induced. INTERPRETATION:
      There is a high prevalence of and substantial under-recognition and under
      treatment of movement disorders in the general community.

PMID- 16297840
TI  - Glycaemia (haemoglobin A1c) and incident ischaemic stroke: the Atherosclerosis
      Risk in Communities (ARIC) Study.
AB  - BACKGROUND: Individuals with diabetes have a raised risk of stroke, but it is
      unclear whether sustained hyperglycaemia contributes to the development of
      cerebrovascular disease. Haemoglobin A1c (HbA(1c)), a measure of long-term
      glycaemia, is strongly related to retinopathy, nephropathy, and neuropathy in
      diabetes. We sought to assess the association between HbA(1c) and stroke in
      people with and without diabetes. METHODS: 10,886 participants without diabetes
      and 1635 participants with diabetes in the ARIC study, who did not have
      cardiovascular disease, were followed up for incident ischaemic stroke over 8-10
      years. We assayed HbA(1c) for all 167 stroke cases and a sample of 680 non-cases
      in the adults without diabetes and for the full cohort of 1635 adults with
      diabetes (including 89 stroke cases). We assessed the relation between HbA(1c)
      concentrations (in tertiles specific for individuals with and without diabetes)
      and incident ischaemic stroke during follow-up using Cox proportional hazards
      models, controlling for risk factors for stroke. FINDINGS: The adjusted relative
      risks of stroke increased with increasing tertile of HbA1c in both adults without
      diabetes (p=0.02) and with diabetes (p<0.0001). Compared with adults without
      diabetes in the lowest tertile of HbA1c, the adjusted relative risks of stroke by
      HbA(1c) tertile were 1.18 (0.70-2.00) and 1.58 (0.94-2.66) in adults without
      diabetes and 1.75 (0.90-3.42), 2.29 (1.24-4.21), and 4.71 (2.69-8.25) in adults
      with diabetes. INTERPRETATION: Raised HbA(1c) could be an independent risk factor
      for stroke in people with and without diabetes, with relative risks similar to
      those previously reported for coronary heart disease.

PMID- 16297841
TI  - Pathogenesis, clinical features, and neurological outcome of cerebral malaria.
AB  - Cerebral malaria is the most severe neurological complication of Plasmodium
      falciparum malaria. Even though this type of malaria is most common in children
      living in sub-Saharan Africa, it should be considered in anybody with impaired
      consciousness that has recently travelled in a malaria-endemic area. Cerebral
      malaria has few specific features, but there are differences in clinical
      presentation between African children and non-immune adults. Subsequent
      neurological impairments are also most common and severe in children.
      Sequestration of infected erythrocytes within cerebral blood vessels seems to be
      an essential component of the pathogenesis. However, other factors such as
      convulsions, acidosis, or hypoglycaemia can impair consciousness. In this review,
      we describe the clinical features and epidemiology of cerebral malaria. We
      highlight recent insights provided by ex-vivo work on sequestration and
      examination of pathological specimens. We also summarise recent studies of
      persisting neurocognitive impairments in children who survive cerebral malaria
      and suggest areas for further research.

PMID- 16297842
TI  - Cholesterol in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common form of neurodegenerative dementia
      and affects up to 15 million people worldwide. Although no single cause of AD has
      been identified, recent research has suggested that several pathogenetic factors
      influence risk and expression. A growing amount of evidence underscores a
      mechanistic link between cholesterol metabolism in the brain and the formation of
      amyloid plaques. Excess brain cholesterol has been associated with increased
      formation and deposition of amyloid-beta peptide from amyloid precursor protein.
      Cholesterol-lowering statins have become a focus of research in AD. Genetic
      polymorphisms associated with pivotal points in cholesterol metabolism in brain
      tissues may contribute to the risk and pathogenesis of AD. In this review, we
      summarise current knowledge of the role of cholesterol metabolism in the
      pathogenesis of AD and examine the potential of statins in the prevention and
      treatment of AD.

PMID- 16297843
TI  - An update on the classification and treatment of vasculitic neuropathy.
AB  - Vasculitic neuropathy usually presents with painful mononeuropathies or an
      asymmetric polyneuropathy of acute or subacute onset. The disorder should be
      classified as being systemic or non-systemic. Systemic vasculitis should be
      further classified into one of the primary and secondary forms. Although specific
      treatment regimens vary among neurologists, basic principles can be applied.
      Corticosteroids and cytotoxic drugs have been the mainstay of treatment for most
      forms of vasculitic neuropathy. Here we discuss dosing, potential side-effects,
      and management recommendations of conventional treatments. New treatments showing
      promise include intravenous immunoglobulin and biological agents and trials of
      the newest treatments are being reviewed. Future trials should compare commonly
      used treatment regimens and better establish the efficacy of newer, potentially
      safer, treatments.

PMID- 16297844
TI  - Drug-induced tremors.
AB  - Tremor is a common complaint for many patients. Caffeine and beta-adrenergic
      agonists are well-recognised drugs that cause or exacerbate tremors. Other
      tremorogenic drugs, such as selective serotonin reuptake inhibitors and tricyclic
      antidepressants, are less well recognised. Recognition of the drugs that can
      cause or exacerbate tremors can help prompt diagnosis, avoids unnecessary tests,
      and allows clinicians to quickly take corrective action (usually by discontinuing
      the tremor-inducing drugs). The aim of this review is to provide clinicians with
      current information on drugs that are associated with tremor and the correct
      treatment of these drug-induced tremors.

PMID- 16297845
TI  - Cerebral hyperperfusion syndrome.
AB  - Cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy is
      characterised by ipsilateral headache, hypertension, seizures, and focal
      neurological deficits. If not treated properly it can result in severe brain
      oedema, intracerebral or subarachnoid haemorrhage, and death. Knowledge of CHS
      among physicians is limited. Most studies report incidences of CHS of 0-3% after
      carotid endarterectomy. CHS is most common in patients with increases of more
      than 100% in perfusion compared with baseline after carotid endarterectomy and is
      rare in patients with increases in perfusion less than 100% compared with
      baseline. The most important risk factors in CHS are diminished cerebrovascular
      reserve, postoperative hypertension, and hyperperfusion lasting more than several
      hours after carotid endarterectomy. Impaired autoregulation as a result of
      endothelial dysfunction mediated by generation of free oxygen radicals is
      implicated in the pathogenesis of CHS. Treatment strategies are directed towards
      regulation of blood pressure and limitation of rises in cerebral perfusion.
      Complete recovery happens in mild cases, but disability and death can occur in
      more severe cases. More information about CHS and early institution of adequate
      treatment are of paramount importance in order to prevent these potentially
      severe complications.

PMID- 16297846
TI  - Accident prediction model for railway-highway interfaces.
AB  - Considerable past research has explored relationships between vehicle accidents
      and geometric design and operation of road sections, but relatively little
      research has examined factors that contribute to accidents at railway-highway
      crossings. Between 1998 and 2002 in Korea, about 95% of railway accidents
      occurred at highway-rail grade crossings, resulting in 402 accidents, of which
      about 20% resulted in fatalities. These statistics suggest that efforts to reduce
      crashes at these locations may significantly reduce crash costs. The objective of
      this paper is to examine factors associated with railroad crossing crashes.
      Various statistical models are used to examine the relationships between crossing
      accidents and features of crossings. The paper also compares accident models
      developed in the United States and the safety effects of crossing elements
      obtained using Korea data. Crashes were observed to increase with total traffic
      volume and average daily train volumes. The proximity of crossings to commercial
      areas and the distance of the train detector from crossings are associated with
      larger numbers of accidents, as is the time duration between the activation of
      warning signals and gates. The unique contributions of the paper are the
      application of the gamma probability model to deal with underdispersion and the
      insights obtained regarding railroad crossing related vehicle crashes.

PMID- 16297847
TI  - [Thoracic kidney: congenital or traumatic origin?].
AB  - The discovery of a thoracic kidney in adult patients can lead to three diagnoses,
      yielding different prognoses and treatment. It can either mean traumatic or
      congenital diaphragmatic hernia, or a congenital ectopic kidney. Intrathoracic
      herniation of the left kidney trough a left diaphragmatic rupture is an
      exceptional discovery. We report the case of a 44 year-old man who met with a car
      accident 20 years ago, and presented abdominal pain. CT-scan showed an
      intrathoracic herniation of the left kidney trough a left posterior diaphragmatic
      rupture. Laparoscopic approach in lateral position showed a traumatic hernia of
      the left costo-diaphragmatic hiatus only containing the left kidney and its
      pedicle. After reduction of herniated left kidney into the abdomen, the hiatus
      was closed by non-resorbable prosthetic mesh. Postoperative course was
      uneventful.

PMID- 16297848
TI  - S-thiolation mimicry: quantitative and kinetic analysis of redox status of
      protein cysteines by glutathione-affinity chromatography.
AB  - S-Glutathionylation is emerging as a novel regulatory and adoptive mechanism by
      which glutathione (GSH or GSSG) conjugation can modify functionally important
      reactive cysteines in redox-sensitive proteins. The dynamics of generation and
      reversal of this modification in cells is poorly understood. This study describes
      the ability and applicability of GSH- and GSSG-affinity matrices to
      quantitatively bind proteins which harbor reactive cysteines and undergo
      glutathionylation. We showed that purified proteins, known to be modified by S
      thiolation, bind to these matrices, are selectively eluted by dithiothreitol and
      rapidly incorporate biotin-labeled GSH or GSSG in vitro. Chromatography of
      extracts from tumor cells that had been treated with oxidants (diamide, H(2)O(2),
      tert-butyl hydroperoxide) on GSH-Sepharose showed the specific binding of many
      proteins, whose levels increased transiently (2- to 6-fold) soon after
      treatments. However, when these cells were post-incubated in drug/oxidant-free
      media, protein binding decreased gradually to control levels over 3-12h, thereby
      demonstrating the central role of cysteine redox status in the binding.
      Immunoblotting of eluates from GSH-Sepharose showed the presence of known (actin,
      ubiquitin-activating enzyme E1, NF-kappaB, and proteasome) and putative (p53,
      glutathione-S-transferase P1) targets for glutathionation. After oxidant
      withdrawal, many of these proteins displayed unique kinetics in their loss of
      binding to GSH-matrix, reflecting their differential abilities to recover from
      cysteine redox changes in cellular milieu. Further, we correlated the kinetics of
      S-thiolation susceptibility of the proteasome and ubiquitin-E1 proteins with
      altered levels of protein ubiquitination in H(2)O(2)-treated cells. Our study
      reveals the hitherto underutilized ability of glutathione matrices for analyzing
      the kinetics of cysteine redox in cellular proteins and allows easy
      identification of S-thiolatable proteins.

PMID- 16297849
TI  - Two pockets in the active site of maize sesquiterpene synthase TPS4 carry out
      sequential parts of the reaction scheme resulting in multiple products.
AB  - One of the most interesting features of terpene synthases is their ability to
      form multiple products with different carbon skeletons from a single prenyl
      diphosphate substrate. The maize sesquiterpene synthase TPS4, for example,
      produces a mixture of 14 different olefinic sesquiterpenes. To understand the
      complex TPS4 reaction mechanism, we modeled the active site cavity and conducted
      docking simulations with the substrate farnesyl diphosphate, several predicted
      carbocation intermediates, and the final reaction products. The model suggests
      that discrete steps of the reaction sequence are controlled by two different
      active site pockets, with the conformational change of the bisabolyl cation
      intermediate causing a shift from one pocket to the other. Site-directed
      mutagenesis and measurements of mutant activity in the presence of (E,E)- and
      (Z,E)-farnesyl diphosphate as substrates were employed to test this model. Amino
      acid alterations in pocket I indicated that early steps of the catalytic process
      up to the formation of the monocyclic bisabolyl cation are probably localized in
      this compartment. Mutations in pocket II primarily inhibited the formation of
      bicylic compounds, suggesting that secondary cyclizations of the bisabolyl cation
      are catalyzed in pocket II.

PMID- 16297850
TI  - Microarray expression profiling and functional characterization of AtTPS genes:
      duplicated Arabidopsis thaliana sesquiterpene synthase genes At4g13280 and
      At4g13300 encode root-specific and wound-inducible (Z)-gamma-bisabolene
      synthases.
AB  - The Arabidopsis thaliana genome contains at least 32 terpenoid synthase (AtTPS)
      genes [Aubourg et al., Mol. Genet. Genom. 267 (2002) 730] a few of which have
      recently been characterized. Based on hierarchical cluster analysis of AtTPS gene
      expression, measured by microarray profiling and validated with published
      expression data, we identified two groups of predominantly root expressed AtTPS
      genes containing five members with previously unknown biochemical functions
      (At4g13280, At4g13300, At5g48110, At1g33750, and At3g29410). Among the root
      expressed AtTPS genes, a pair of tandem-organized genes, At4g13280 (AtTPS12) and
      At4g13300 (AtTPS13), shares 91% predicted amino acid identity indicating recent
      gene duplication. Bacterial expression of cDNAs and enzyme assays showed that
      both At4g13280 and At4g13300 encode sesquiterpene synthases catalyzing the
      conversion of farnesyl diphosphate to (Z)-gamma-bisabolene and the additional
      minor products E-nerolidol and alpha-bisabolol. Expression of beta-glucuronidase
      (GUS) reporter gene fused to upstream genomic regions of At4g13280 or At4g13300
      showed constitutive promoter activities in the cortex and sub-epidermal layers of
      Arabidopsis roots. In addition, highly localized promoter activities were found
      in leaf hydathodes and flower stigmata. Mechanical wounding of Arabidopsis leaves
      induced local expression of At4g13280 and At4g13300. The functional
      characterization of At4g13280 gene product AtTPS12 and At4g13230 gene product
      AtTPS13 as (Z)-gamma-bisabolene synthases, together with the recent
      characterization of two flower-specific AtTPS [At5g23960 and At5g44630; Tholl et
      al., Plant J. 42 (2005) 757], concludes the biochemical functional annotation of
      all four predicted Arabidopsis sesquiterpene synthase genes. Our data suggest
      biological functions for At4g13280 and At4g13300 in the rhizosphere with
      additional roles in aerial plant tissues.

PMID- 16297851
TI  - Solution structure of a common substrate mimetic of cyclooxygenase-downstream
      synthases bound to an engineered thromboxane A2 synthase using a high-resolution
      NMR technique.
AB  - Understanding the docking mechanism of the common substrate, prostaglandin H(2)
      (PGH(2)), into the active sites of different cyclooxygenase(COX)-downstream
      synthases is a key step toward uncovering the molecular basis of the
      isomerization of PGH(2) to different prostanoids. A high-resolution NMR
      spectroscopy was used to determine the conformational changes and solution 3D
      structure of U44069, a PGH(2) analogue, bound to one of the COX-downstream
      synthases-an engineered thromboxane A(2) synthase (TXAS). The dynamic binding was
      clearly observed by (1)D NMR titration. The detailed conformational change and 3D
      structure of U44069 bound to the TXAS were demonstrated by 2D (1)H NMR
      experiments using transferred NOEs. Through the assignments for the 2D (1)H NMR
      spectra, TOCSY, DQF-COSY, NOESY, and the structural calculations based on the NOE
      constraints, they demonstrated that the widely open conformation with a triangle
      shape of the free U44069 changed to a compact structure with an oval shape when
      bound to the TXAS. The putative substrate-binding pocket of the TXAS model fits
      the conformation of the TXAS-bound U44069 appropriately, but could not fit the
      free form of U44069. It was the first to provide structural information for the
      dynamic docking of the PGH(2) mimic of the TXAS in solution, and to imply that
      PGH(2) undergoes conformational changes when bound to different COX-downstream
      synthases, which may play important roles in the isomerization of PGH(2) to
      different prostanoids. The NMR technique can be used as a powerful tool to
      determine the conformations of PGH(2) bound to other COX-downstream synthases.

PMID- 16297852
TI  - Bcl-2 but not clusterin/apolipoprotein J protected human diploid fibroblasts and
      immortalized keratinocytes from ceramide-induced apoptosis: role of p53 in the
      ceramide response.
AB  - The role of clusterin/apolipoprotein J (Clu/ApoJ) and Bcl-2 on C(2)-ceramide
      induced apoptosis of embryonic human diploid fibroblasts, MRC-5 and immortalized
      adult skin keratinocytes, HaCaT was investigated. C(2)-ceramide-induced apoptosis
      of HaCaT in a time- and dose-dependent manner, while in MRC-5 only at higher
      concentrations. There was a dose-dependent accumulation of Clu/ApoJ and
      downregulation of Bcl-2 which correlated with C(2)-ceramide-induced apoptosis of
      MRC-5. While overexpression of Bcl-2 suppressed C(2)-ceramide-mediated apoptosis
      in both cell types, Clu/ApoJ failed to do so, accessed by morphological changes,
      DNA fragmentation and PARP cleavage. There was no change in the expression of
      endogenous p53 or p21(Waf1/Cip1) upon C(2)-ceramide treatment of MRC-5. However,
      mutant p53(143ala) increased the sensitivity of MRC-5 to C(2)-ceramide-induced
      apoptosis by markedly downregulating Bcl-2, pointing to a role for p53. These
      results suggested that whereas downregulation of Bcl-2 may be a crucial factor
      involved in C(2)-ceramide-induced apoptosis, accumulation of Clu/ApoJ may be a
      signal of stress response. Moreover, the ceramide-activated apoptotic pathway may
      be regulated by p53.

PMID- 16297853
TI  - Role of eosinophil peroxidase in host defense and disease pathology.
AB  - Three unusual substrates-bromide (Br(-)), nitrite (NO(2)(-)), and thiocyanate
      (SCN(-))-compete for oxidation by eosinophil peroxidase (EPO) in physiologic
      fluids in the presence of H(2)O(2) to yield, respectively, hypobromous acid
      (HOBr), nitrogen dioxide (NO(2)()), or hypothiocyanous acid (HOSCN). These
      oxidant products have strikingly different reactivities: HOBr and NO(2)() are
      potent, widely reactive, membrane-lytic oxidants whereas HOSCN is a weak, SH
      specific oxidant that penetrates into cells and imposes an intracellular oxidant
      stress that can activate kinase pathways and transcription factors that
      profoundly influence gene expression in host cells. All three oxidants are lethal
      for pathogens. SCN(-) is the strongly preferred substrate for the EPO/H(2)O(2).
      Specific biomarkers document that EPO-dependent oxidants are generated at sites
      of inflammation, but direct evidence that these oxidants cause disease is
      confined to the observation that an EPO knockout mouse line has dramatically less
      pathologic damage than do wild type animals in a murine model of ulcerative
      colitis.

PMID- 16297855
TI  - Chemistry and biology of human peroxidases.

PMID- 16297854
TI  - A region C-terminal to the proline-rich core of p47phox regulates activation of
      the phagocyte NADPH oxidase by interacting with the C-terminal SH3 domain of
      p67phox.
AB  - Activation of the phagocyte NADPH oxidase requires the regulatory proteins
      p47(phox) and p67(phox), each harboring two SH3 domains. p67(phox) interacts with
      p47(phox) via simultaneous binding of the p67(phox) C-terminal SH3 domain to both
      the proline-rich region (PRR) of amino acid residues 360-369 and its C-terminally
      flanking region of p47(phox); the role of the interaction in oxidase regulation
      has not been fully understood. Here we show that the p47(phox)-p67(phox)
      interaction is disrupted not only by deletion of the PRR but also by substitution
      for basic residues in the extra-PRR (K383E/K385E). The substitution impaired
      oxidase activation partially in vitro and much more profoundly in vivo,
      indicating the significance of the p47(phox) extra-PRR. Replacement of Ser-379 in
      the extra-PRR, a residue known to undergo phosphorylation in stimulated cells, by
      aspartate attenuates the interaction and thus results in a defective superoxide
      production, suggesting that phosphorylation of Ser-379 is involved in oxidase
      regulation.

PMID- 16297856
TI  - The relationship between phenylthiocarbamide (PTC) and 6-n-propylthiouracil
      (PROP) taster status and taste thresholds for sucrose and quinine.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship of taster
      status with taste detection and recognition thresholds for sucrose and quinine.
      DESIGN: Sixty-nine subjects (35 men and 34 women; mean age, 23.9+/-1.2 years)
      were included. Stimulus fluids were prepared, one each for phenylthiocarbamide
      (PTC), 6-n-propylthiouracil (PROP), sucrose and quinine HCl. In each series,
      successive solutions, which comprised a total of 15 grades, differed by 0.25log
      units of the molar concentration. Two concentrations of NaCl (0.32 and 1.0 M)
      were prepared. The subjects were classified as nontasters and tasters using their
      PTC and PROP perceptions. Tasters were classified as medium-tasters and
      supertasters by the ratio of perceived bitterness of above-threshold PROP
      relative to the perceived saltiness of NaCl (PROP ratio). Taste detection and
      recognition thresholds for sucrose and quinine were determined by standard two
      alternative forced choice trials. A Student's t-test, a Pearson's correlation
      analysis and linear contrasts in a one-way analysis of variance (ANOVA) were
      used. RESULTS: The percentages of nontaster, medium-taster and supertaster were
      13, 70 and 17%, respectively. There were no significant gender differences in the
      taste detection and recognition thresholds for sucrose and quinine. The threshold
      for PTC and PROP showed significant correlations with taste threshold for
      quinine. Linear contrast in one-way ANOVA showed that the greater the value of
      PROP ratio, the more sensitive to sweet and bitter tastes (p<0.001). CONCLUSION:
      The PTC and PROP taster status is closely related with taste detection and
      recognition thresholds for sucrose and quinine.

PMID- 16297857
TI  - EPR study of lipid phase in renal cortical membrane organelles from intact and
      cadmium-intoxicated rats.
AB  - Numerous studies have demonstrated various structure/function correlations at the
      level of transport proteins in the kidney cell membranes and various
      intracellular organelles. However, characterization of the lipid phase of these
      membranes is rare. Here, we report the differences in lipid organization and
      dynamics of the brush-border membranes (BBM), basolateral membranes (BLM) and
      endocytotic vesicles (EV), isolated from the kidney cortex of intact rats,
      studied with the EPR spectroscopy of the spin-labeled membrane lipids. The EPR
      spectra were analyzed by comparing experimentally observed line shapes with the
      line shapes calculated according to the theoretical model developed for liquid
      crystals. In the fitting procedure, three different lipid domains were assumed,
      which revealed clear differences in the lipid ordering and rotational correlation
      times, as well as in the lipid partition of these domains in each of the three
      types of membranes. A similar approach, used to compare the spectroscopic
      characteristics of BBM from control and cadmium-intoxicated rats, showed
      significantly changed ordering and increased molecular mobility in the lipid
      phase of BBM from Cd-treated animals. As tested by an established fluorescence
      assay, the Cd-induced changes in the lipid mobility co localized with
      approximately 5-fold higher conductance of BBM for potassium, with unchanged
      conductance for protons.

PMID- 16297858
TI  - Downregulation of MDM2 expression by RNAi inhibits LoVo human colorectal
      adenocarcinoma cells growth and the treatment of LoVo cells with mdm2siRNA3
      enhances the sensitivity to cisplatin.
AB  - To investigate the biological effect of mdm2 in human colorectal adenocarcinoma
      LoVo cells, three mdm2siRNA constructions were recombined and transient
      transfected into human colorectal adenocarcinoma LoVo cells with low
      differentiation character in vitro. The results showed that mdm2siRNA3 reduced
      mRNA level of mdm2 and protein level of mdm2, leading to proliferation inhibition
      on LoVo cells, and reduced tumor growth in nude mice. It was found that depletion
      of MDM2 in this pattern promoted apoptosis of LoVo cells and Cisplatin (DDP)
      treated in the mdm2siRNA3 transfected cell population would result in a
      substantial decrease by MTT colorimetry. Decreasing the MDM2 protein level in
      LoVo cells by RNAi could significantly inhibit tumor growth both in vitro and in
      vivo, which indicated that mdm2 gene played a definite role in the development
      and aggressiveness of human colon carcinoma. It also could be a therapeutic
      target in colorectal carcinoma. The synergistic activation of RNAi and cell
      toxicity agents indicated that the combination of chemotherapy and gene therapy
      will be a promising approach in the future.

PMID- 16297859
TI  - Association between endothelin-1 and collagen deposition in db/db diabetic mouse
      kidneys.
AB  - Endothelin-1 has been implicated in diabetic kidney injury, but there are few
      firm data establishing the temporal and spatial expression of kidney endothelin-1
      in diabetes. We performed an immunohistochemical and histopathological analysis
      to determine endothelin-1 peptide expression in the kidneys of diabetic db/db
      mice and non-diabetic db/m controls. Diabetic mice were studied at 8 weeks,
      before histological damage is evident, and again at 16 weeks, when significant
      glomerular injury has occurred. Urinary endothelin-1 was 6.2- and 3.6-fold higher
      in 8- and 16-week diabetic mice compared to age-matched controls (P<0.01 db/db
      vs. db/m). Compared to non-diabetic kidneys, immunoreactive endothelin-1 was
      first elevated 2.5-fold (P=0.02) in the tubulointerstitial compartment at 8-week
      and remained high (3.8-fold, P<0.01) at 16 weeks. In contrast, glomerular
      endothelin-1 was elevated 3.2-fold (P=0.03) only in 16-week diabetic mice.
      Glomerular and tubulointerstitial endothelin-1 were unchanged in 8- and 16-week
      non-diabetic mice. Elevated endothelin-1 in diabetic mice associated temporally
      and spatially with collagen deposition, especially in the tubulointerstitial
      compartment. The localization of kidney endothelin-1 is consistent with a role
      for this peptide in renal fibrogenesis. These results also highlight the
      potential role of ET-1 in the pathogenesis of early tubulointerstitial changes in
      diabetes.

PMID- 16297860
TI  - Simvastatin enhances bone morphogenetic protein receptor type II expression.
AB  - Statins confer therapeutic benefits in systemic and pulmonary vascular diseases.
      Bone morphogenetic protein (BMP) receptors serve essential signaling functions in
      cardiovascular development and skeletal morphogenesis. Mutations in BMP receptor
      type II (BMPR2) are associated with human familial and idiopathic pulmonary
      arterial hypertension, and pathologic neointimal proliferation of vascular
      endothelial and smooth muscle cells within small pulmonary arteries. In severe
      experimental pulmonary hypertension, simvastatin reversed disease and conferred a
      100% survival advantage. Here, modulation of BMPR2 gene expression by simvastatin
      is characterized in human embryonic kidney (HEK) 293T, pulmonary artery smooth
      muscle, and lung microvascular endothelial cells (HLMVECs). A 1.4kb BMPR2
      promoter containing Egr-1 binding sites confers reporter gene activation in 293T
      cells which is partially inhibited by simvastatin. Simvastatin enhances steady
      state BMPR2 mRNA and protein expression in HLMVEC, through posttranscriptional
      mRNA stabilization. Simvastatin induction of BMPR2 expression may improve BMP
      BMPR2 signaling thereby enhancing endothelial differentiation and function.

PMID- 16297861
TI  - Cloning of a sea urchin sarco/endoplasmic reticulum Ca2+ ATPase.
AB  - Sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), a vesicular integral membrane
      protein, is the best-characterized member of the P-type ion translocating ATPase
      superfamily. Here we describe the cloning and structural analysis of a sea urchin
      SERCA (suSERCA) cloned from testis cDNA. The approximately 112 kDa suSERCA is
      1022 amino acids with approximately 70% identity and 80% similarity to all known
      mammalian SERCA isoforms. suSERCA shares all the structural features of mammalian
      SERCAs, including domains: A, actuator; N, nucleotide-binding; and P,
      phosphorylation, and also 10 transmembrane helices. Like human SERCA2, the
      suSERCA has a possible 11th transmembrane segment in its extreme C-terminus. The
      alignment of three sequences (suSERCA, human SERCA2, and rabbit SERCA1a) shows
      that the Ca2+ binding residues and kinks (required to form the ion-binding
      pocket) are 100% conserved. The annotated suSERCA gene consists of 24 exons
      separated by 23 introns and is approximately 30 kb. Western blots show that
      suSERCA is present in sea urchin eggs and testis, but not in mature spermatozoa.
      Treatment of live sperm with SERCA inhibitors has no effect on intracellular
      calcium, suggesting the absence of SERCA in sea urchin spermatozoa.

PMID- 16297862
TI  - Autoantigen Ro52 is an E3 ubiquitin ligase.
AB  - Anti-Ro/SSA antibodies are classic autoantibodies commonly found in patients with
      Sjogren's syndrome, a chronic autoimmune disease characterized by dryness of the
      eyes and mouth. The autoantibodies recognize a RING-finger protein, Ro52, whose
      function is still unknown. Since many RING-finger proteins have been identified
      as E3 ubiquitin ligases, this study was designed to determine whether Ro52
      functions as an E3 ubiquitin ligase. For this purpose, recombinant Ro52 was
      purified from bacterial lysate and used to investigate its activity of E3
      ubiquitin ligase in vitro. Its enzymatic activity was also tested in HEK293T
      cells using wild-type Ro52 and its RING-finger mutant. Our results indicated that
      Ro52 ubiquitinates itself in cooperation with E2 ubiquitin-conjugating enzyme
      UbcH5B, thereby validating that Ro52 is a RING-finger-type E3 ubiquitin ligase.
      Importantly, this ubiquitin modification is predominantly monoubiquitination,
      which does not target Ro52 to the proteasome for degradation.

PMID- 16297863
TI  - NK sensitivity of neuroblastoma cells determined by a highly sensitive coupled
      luminescent method.
AB  - The measurement of natural killer (NK) cells toxicity against tumor or virus
      infected cells especially in cases with small blood samples requires highly
      sensitive methods. Here, a coupled luminescent method (CLM) based on
      glyceraldehyde-3-phosphate dehydrogenase release from injured target cells was
      used to evaluate the cytotoxicity of interleukin-2 activated NK cells against
      neuroblastoma cell lines. In contrast to most other methods, CLM does not require
      the pretreatment of target cells with labeling substances which could be toxic or
      radioactive. The effective killing of tumor cells was achieved by low
      effector/target ratios ranging from 0.5:1 to 4:1. CLM provides highly sensitive,
      safe, and fast procedure for measurement of NK cell activity with small blood
      samples such as those obtained from pediatric patients.

PMID- 16297864
TI  - Reconstitution of beta-carotene hydroxylase activity of thermostable CYP175A1
      monooxygenase.
AB  - CYP175A1 is a thermostable P450 Monooxygenase from Thermus thermophilus HB27,
      demonstrating in vivo activity towards beta-carotene. Activity of CYP175A1 was
      reconstituted in vitro using artificial electron transport proteins. First
      results were obtained in the mixture with a crude Escherichia coli cell extract
      at 37 degrees C. In this system, beta-carotene was hydroxylated to beta
      cryptoxanthin. The result indicated the presence of electron transport enzymes
      among the E. coli proteins, which are suitable for CYP175A1. However, upon in
      vitro reconstitution of CYP175A1 activity with purified recombinant flavodoxin
      and flavodoxin reductase from E. coli, only very low beta-cryptoxanthin
      production was observed. Remarkably, with another artificial electron transport
      system, putidaredoxin and putidaredoxin reductase from Pseudomonas putida,
      purified CYP175A1 enzyme hydroxylated beta-carotene at 3- and also 3'-positions,
      resulting in beta-cryptoxanthin and zeaxanthin. Under the optimal reaction
      conditions, the turnover rate of the enzyme reached 0.23 nmol beta-cryptoxanthin
      produced per nmol P450 per min.

PMID- 16297865
TI  - Genomic structure and promoter activity of the E1AF gene, a member of the ETS
      oncogene family.
AB  - E1AF is a member of the ETS oncogene family and is thought to be a human
      homologue of mouse PEA3. We have isolated a genomic clone of E1AF and analyzed
      the promoter activity of its 5'-flanking region. We identified a variation in
      exon 1, which depends on the cell type. There was no typical TATA box in the 5'
      flanking region, but putative binding sites of a number of transcription factors
      including PEA3 as well as CAAT boxes were seen. A luciferase reporter assay
      indicated that the 5'-flanking region possesses promoter activity. Northern blot
      studies demonstrated significant expression of the E1AF gene in restricted
      tissues such as the pituitary gland, placenta, and fetal kidney. Moreover, the
      E1AF promoter was activated by E1AF itself and estrogen receptor. These findings
      suggest that E1AF is a housekeeping gene, whose expression is controlled in
      specific tissues.

PMID- 16297866
TI  - A modified, dual reporter TOXCAT system for monitoring homodimerization of
      transmembrane segments of proteins.
AB  - The TOXCAT assay system developed by Russ and Engelman [TOXCAT: a measure of
      transmembrane helix association in a biological membrane, Proc. Natl. Acad. Sci.
      USA 96 (1999) 863-868] provides an in vivo means of selecting for and evaluating
      the strength of interaction between identical transmembrane alpha-helices. In the
      course of utilizing TOXCAT to study the architecture of a sodium channel
      hNa(V)1.5, an apparently strong dimerization of two of its putative transmembrane
      segments was revealed. Following random mutagenesis of these regions, several
      amino acids critical for the observed dimerizations were identified. In order to
      develop a more efficient means of isolating mutations which specifically disrupt
      dimerization of these transmembrane segments without affecting their membrane
      targeting properties, we developed a modification to the original TOXCAT design
      in which the C-terminal maltose binding protein moiety is replaced by the beta
      lactamase. We show that this assay system is capable of simultaneously monitoring
      the integrity of the chimeric protein, its membrane insertion activity, and the
      ability of the transmembrane segment under study to dimerize.

PMID- 16297867
TI  - Functional expression of the maize mitochondrial URF13 down-regulates galactose
      induced GAL1 gene expression in Saccharomyces cerevisiae.
AB  - Genes for the enzymes that metabolize galactose in Saccharomyces cerevisiae are
      strongly induced by galactose and tightly repressed by glucose. Because glucose
      also represses mitochondrial activity, we examined if derepression of the GAL1
      galactokinase gene requires physiologically active mitochondria. The effect of
      mitochondria on the expression of GAL1 was analyzed by a novel approach in which
      the activity of the organelles was altered by functional expression of URF13, a
      mitochondrial protein unique to the Texas-type cytoplasmic male sterility
      phenotype in maize. Mitochondrial targeting and functional expression of the
      URF13 protein in yeast result in a decrease of the mitochondrial membrane
      potential similar to those observed in cells treated with mitochondrial
      inhibitors such as antimycin A or sodium azide. Activation of URF13 in galactose
      induced cells results in the inhibition of GAL1 expression in the absence of
      repressing concentrations of glucose. Our data reveal the existence of a
      regulatory pathway that connects the derepression of the GAL1 gene with
      mitochondrial activity.

PMID- 16297868
TI  - Functional insights from the structural modelling of a small Fe-hydrogenase.
AB  - Recently, a novel Fe-hydrogenase from a high rate of hydrogen producing
      Enterobacter cloacae strain IIT-BT08 was identified and partially characterized.
      This 147 residue protein was found to be much smaller than previously known Fe
      hydrogenases, yet retaining a high catalytic activity. We predicted the structure
      of this protein and found it to be structurally similar to one of the two sub
      domains containing the catalytic H-cluster so far jointly present in all other Fe
      hydrogenases. This novel architecture allows a tentative explanation of protein
      function with the high rate of catalytic activity being due to a missing
      regulatory sub-domain, presumably allowing higher enzymatic activity at the cost
      of greater exposure to oxygen inactivation. This new insight may improve our
      understanding of the molecular and functional organization of other, more complex
      Fe-hydrogenases.

PMID- 16297869
TI  - Cholecystokinin stimulates the recruitment of the Src-RhoA-phosphoinositide 3
      kinase pathway by Vav-2 downstream of G(alpha13) in pancreatic acini.
AB  - In isolated rat pancreatic acini, Src, RhoA, PI3-K, Vav-2, G(alpha12), and
      G(alpha13) were detected by immunoblotting. CCK enhanced the levels of these
      proteins, and the levels of Src and RhoA were reduced by the Src inhibitor
      herbimycin A and the Rho inhibitor pravastatin. The PI3-K inhibitor wortmannin
      reduced the level of PI3-K. These inhibitors also decreased amylase secretion in
      CCK-treated pancreatic acini without altering basal secretion.
      Immunoprecipitation studies indicated that CCK caused Src to associate with Vav
      2, RhoA, and PI3-K and RhoA and Src to associate with Vav-2. Ras, RasGAP, and SOS
      did not coimmunoprecipitate with Vav-2, and RasGAP and SOS did not
      coimmunoprecipitate with RhoA. CCK also enhanced Vav-2 and RhoA to
      coimmunoprecipitate with G(alpha13). We conclude that CCK stimulates the
      recruitment of the Src-RhoA-PI3-K signaling pathway by Vav-2 downstream of
      G(alpha13) in pancreatic acini.

PMID- 16297871
TI  - Nitric oxide protects against mitochondrial permeabilization induced by
      glutathione depletion: role of S-nitrosylation?
AB  - Nitric oxide (NO) is known to mediate a multitude of biological effects including
      inhibition of respiration at cytochrome c oxidase (COX), formation of
      peroxynitrite (ONOO-) by reaction with mitochondrial superoxide (O2*-), and S
      nitrosylation of proteins. In this study, we investigated pathways of NO
      metabolism in lymphoblastic leukemic CEM cells in response to glutathione (GSH)
      depletion. We found that NO blocked mitochondrial protein thiol oxidation,
      membrane permeabilization, and cell death. The effects of NO were: (1)
      independent of respiratory chain inhibition since protection was also observed in
      CEM cells lacking mitochondrial DNA (rho0) which do not possess a functional
      respiratory chain and (2) independent of ONOO- formation since nitrotyrosine (a
      marker for ONOO- formation) was not detected in extracts from cells treated with
      NO after GSH depletion. However, NO increased the level of mitochondrial protein
      S-nitrosylation (SNO) determined by the Biotin Switch assay and by the release of
      NO from mitochondrial fractions treated with mercuric chloride (which cleaves SNO
      bonds to release NO). In conclusion, these results indicate that NO blocks cell
      death after GSH depletion by preserving the redox status of mitochondrial protein
      thiols probably by a mechanism that involves S-nitrosylation of mitochondrial
      protein thiols.

PMID- 16297870
TI  - Effects of different zinc finger transcription factors on genomic targets.
AB  - We have developed a novel vector system for the efficient assembly of polydactyl
      zinc fingers. Next to proteins that possess short canonical TGEKP linkers between
      all constituting zinc fingers we constructed proteins with longer, 12 amino acid
      linkers between two three-finger (3F) units and between three two-finger (2F)
      units. Fusions of these zinc finger domains with the VP16 activation domain were
      tested for their ability to regulate a repressed genomic locus containing
      contiguous or noncontiguous zinc finger binding sites in yeast. In contrast to
      other studies, which were mostly confined to in vitro tests, we did not obtain
      evidence that superior artificial zinc finger transcription factors need to
      contain longer linkers between individual fingers. For the regulation of genomic
      loci, canonical linkers within a highly regular backbone in combination with a
      contiguous 18 base pair DNA target site were found to provide a sound base for
      polydactyl zinc finger design.

PMID- 16297872
TI  - Intestinal-fatty acid binding protein and lipid transport in human intestinal
      epithelial cells.
AB  - Intestinal-fatty acid binding protein (I-FABP) is a 14-15 kDa cytoplasmic
      molecule highly expressed in the enterocyte. Although different functions have
      been proposed for various FABP family members, the specific function of I-FABP in
      human intestine remains unclear. Here, we studied the role of I-FABP in
      molecularly modified normal human intestinal epithelial cells (HIEC-6). cDNA
      transfection resulted in 90-fold I-FABP overexpression compared to cells treated
      with empty pQCXIP vector. The high-resolution immunogold technique revealed
      labeling mainly in the cytosol and confirmed the marked phenotype abundance of I
      FABP in cDNA transfected cells. I-FABP overexpression was not associated with
      alterations in cell proliferation and viability. Studies using these transfected
      cells cultured with [14C]oleic acid did not reveal higher efficiency in de novo
      synthesis or secretion of triglycerides, phospholipids, and cholesteryl esters
      compared to cells treated with empty pQCXIP vector only. Similarly, the
      incubation with [35S]methionine did not disclose a superiority in the biogenesis
      of apolipoproteins (apo) A-I, A-IV, B-48, and B-100. Finally, cells transfected
      with I-FABP did not exhibit an increased production of chylomicrons, VLDL, LDL,
      and HDL. Our observations establish that I-FABP overexpression in normal HIEC-6
      is not related to cell proliferation, lipid esterification, apo synthesis, and
      lipoprotein assembly, and, therefore, exclude its role in intestinal fat
      transport.

PMID- 16297873
TI  - Anti-inflammatory effects of IL-4 and dynamic compression in IL-1beta stimulated
      chondrocytes.
AB  - Mechanical loading can counteract inflammatory pathways induced by IL-1beta by
      inhibiting *NO and PGE2, catabolic mediators known to be involved in cartilage
      degradation. The current study investigates the potential of dynamic compression,
      in combination with the anti-inflammatory cytokine, IL-4, to further abrogate the
      IL-1beta induced effects. The data presented demonstrate that IL-4 alone can
      inhibit nitrite release in the presence and absence of IL-1beta and partially
      reverse the IL-1beta induced PGE2 release. When provided in combination, IL-4 and
      dynamic compression could further abrogate the IL-1beta induced nitrite and PGE2
      release. IL-1beta inhibited [3H]thymidine incorporation and this effect could be
      reversed by IL-4 or dynamic strain alone or both in combination. By contrast,
      35SO4 incorporation was not influenced by IL-4 and/or dynamic strain in IL-1beta
      stimulated constructs. IL-4 and mechanical loading may therefore provide a
      potential protective mechanism for cartilage destruction as observed in OA.

PMID- 16297874
TI  - Vdelta1 T cell receptor binds specifically to MHC I chain related A: molecular
      and biochemical evidences.
AB  - Human MHC class I chain-related A (MICA) is a tumor-associated antigen that can
      be recognized by Vdelta1 subset of tumor-infiltrating gammadelta T cells. We
      previously reported that immobilized recombinant MICA protein could induce the
      proliferation of tumor-infiltrating Vdelta1 gammadelta T cells in vitro. But
      there has been no direct evidence showing the engagement of gammadelta T cell
      receptors (TCR) of the induced cells with MICA. In the current investigation, we
      show that MICA induces specific cytolytic activity of the expanded gammadelta T
      cells. We expressed the coupled V domains from the MICA-induced T cells as a
      single polypeptide chain Vdelta Vgamma TCR (gammadelta scTCR). Such scTCR can
      specifically bind MICA of HeLa cells. Direct interaction of gammadelta scTCRs
      with in vitro expressed MICA was monitored using an IAsys biosensor. We found
      that the Vdelta1 scTCR can specifically bind to immobilized MICA molecule and
      MICA alpha1alpha2 domains are responsible for the binding reaction.

PMID- 16297876
TI  - PKCalpha expression regulated by Elk-1 and MZF-1 in human HCC cells.
AB  - Our previous study found that PKCalpha was highly expressed in the poor
      differentiated human HCC cells and associated with cell migration and invasion.
      In this study, we further investigated the gene regulation of this enzyme. We
      showed that PKCalpha expression enhancement in the poor-differentiated human HCC
      cells was found neither by DNA amplification nor by increasing mRNA stability
      using differential PCR and mRNA decay assays. After screening seven transcription
      factors in the putative cis-acting regulatory elements of human PKCalpha
      promoters, only Elk-1 and MZF-1 antisense oligonucleotide showed a significant
      reduction in the PKCalpha mRNA level. They also reduced cell proliferation, cell
      migratory and invasive capabilities, and DNA binding activities in the PKCalpha
      promoter region. Over-expression assay confirmed that the PKCalpha expression may
      be modulated by these two factors at the transcriptional level. Therefore, these
      results may provide a novel mechanism for PKCalpha expression regulation in human
      HCC cells.

PMID- 16297875
TI  - Tissue Prx I in the protection against Fe-NTA and the reduction of nitroxyl
      radicals.
AB  - Peroxiredoxin I (Prx I) is a key cytoplasmic peroxidase that reduces
      intracellular hydroperoxides in concert with thioredoxin. To study the role of
      tissue Prx I in protection from oxidative stress, we generated Prx I-/- mice by
      gene trapping. We then evaluated the acute-phase tissue damage caused by ferric
      nitrilotriacetate (Fe-NTA). Increases in serum aspartate aminotransferase and
      alanine aminotransferase levels were significantly greater in Prx I-/- than wild
      type mice, 4 and 12 h after the injection of Fe-NTA. Using real-time EPR imaging,
      we examined the reduction of the stable paramagnetic nitroxyl radical 3-carbamoyl
      2,2,5,5-tetramethylpyrrolidine-1-oxyl in vivo, and found that the half-life of
      this spin probe in the liver and kidney was significantly prolonged in the Prx I
      /- mice. These results demonstrate that Prx I-/- mice have less reducing activity
      and are more susceptible to the damage mediated by reactive oxygen species in
      vivo than wild-type mice.

PMID- 16297877
TI  - Ginsenoside Rf, a component of ginseng, regulates lipoprotein metabolism through
      peroxisome proliferator-activated receptor alpha.
AB  - We investigated whether ginseng regulates lipoprotein metabolism by altering
      peroxisome proliferator-activated receptor alpha (PPARalpha)-mediated pathways,
      using a PPARalpha-null mouse model. Administration of ginseng extract,
      ginsenosides, and ginsenoside Rf (Rf) to wild-type mice not only significantly
      increased basal levels of hepatic apolipoprotein (apo) A-I and C-III mRNA
      compared with wild-type controls, but also substantially reversed the reductions
      in mRNA levels of apo A-I and C-III expected following treatment with the potent
      PPARalpha ligand Wy14,643. In contrast, no effect was detected in the PPARalpha
      null mice. Testing of eight main ginsenosides on PPARalpha reporter gene
      expression indicated that Rf was responsible for the effects of ginseng on
      lipoprotein metabolism. Furthermore, the inhibition of PPARalpha-dependent
      transactivation by Rf seems to occur at the level of DNA binding. These results
      demonstrate that ginseng component Rf regulates apo A-I and C-III mRNA and the
      actions of Rf on lipoprotein metabolism are mediated via interactions with
      PPARalpha.

PMID- 16297878
TI  - Quaternary assembly and crystal structure of GDP-D-mannose 4,6 dehydratase from
      Paramecium bursaria Chlorella virus.
AB  - GDP-D-mannose 4,6 dehydratase is the first enzyme in the de novo biosynthetic
      pathway of GDP-L-fucose, the activated form of L-fucose, a monosaccharide found
      in organisms ranging from bacteria to mammals. We determined the three
      dimensional structure of GDP-D-mannose 4,6 dehydratase from the Paramecium
      bursaria Chlorella virus at 3.8A resolution. Unlike other viruses that use the
      host protein machinery to glycosylate their proteins, P. bursaria Chlorella virus
      modifies its structural proteins using many glycosyltransferases, being the first
      virus known to encode enzymes involved in sugar metabolism. P. bursaria Chlorella
      virus GDP-D-mannose 4,6 dehydratase belongs to the short-chain
      dehydrogenase/reductase protein superfamily. Accordingly, the family fold and the
      specific Thr, Tyr, and Lys catalytic triad are well conserved in the viral
      enzyme.

PMID- 16297879
TI  - eNOS, COX-2, and prostacyclin production are impaired in endothelial cells from
      diabetics.
AB  - The vascular endothelium is a well-recognized target of damage for factors
      leading to increased cardiovascular risk. Among the agents playing an important
      role in cardiovascular homeostasis, nitric oxide and prostacyclin represent key
      markers of endothelial integrity. In the present work, we report for the first
      time the reduced expression of both endothelial nitric oxide synthase and
      cyclooxygenase-2 (COX-2) proteins, as well as decreased prostacyclin production,
      in unstimulated human endothelial cells from insulin-dependent diabetic mothers
      when compared to cells from non-diabetic, control subjects. According to a major
      role of COX-2 as a source of prostacyclin production even in unstimulated
      endothelial cells, prostacyclin production was concentration-dependently
      inhibited by the selective COX-2 inhibitor SC236. Overall, our results suggest a
      possible link between reduced endothelial COX-2 and NO-synthase expression and
      the increased risk of cardiovascular diseases affecting diabetic patients, and
      point to the use of endothelial cells from diabetic patients as a tool for
      investigating early dysfunction in pathological endothelium.

PMID- 16297880
TI  - Activated nuclear transcription factor kappaB in patients with myocarditis and
      dilated cardiomyopathy--relation to inflammation and cardiac function.
AB  - OBJECTIVES AND BACKGROUND: Myocarditis is caused by various agents and autoimmune
      processes. It is unknown whether viral genome persistence represents inactive
      remnants of previous infections or whether it is attributed to ongoing adverse
      processes. The latter also applies to the course of autoimmune myocarditis. One
      principal candidate for an adverse remodeling is nuclear factor-kappaB
      (NFkappaB). METHODS: A total of 93 patients with suspected
      myocarditis/cardiomyopathy was examined. Hemodynamics were assessed by
      echocardiography as well as right and left heart catheterization. Endomyocardial
      biopsies were taken from the left ventricle. Biopsies were examined by
      immunohistochemistry and PCR for viral genomes. Selective immunostaining of
      activated NFkappaB was performed. RESULTS: NFkappaB was increased in patients
      with myocarditis when compared with controls (11.1+/-7.1% vs. 5.0+/-5.3%,
      P<0.005) whereas dilated cardiomyopathy showed no significant increase. Patients
      with myocarditis and preserved left ventricular function exhibited increased
      activated NFkappaB when compared with reduced function (r2=0.72, P<0.001). In
      parallel, inverse correlation of NFkappaB and left ventricular enddiasstolic
      volume was found (r2=0.43, P<0.02). Increased activated NFkappaB was found in
      adenovirus persistence when compared with controls (P=0.001). Only a trend of
      increased NFkappaB activation was seen in cytomegalovirus persistence. Parvovirus
      B19 persistence did not affect NFkappaB activation. CONCLUSIONS: Increased
      activation of NFkappaB is related to inflammatory processes in myocarditis. Since
      activated NFkappaB correlates with left ventricular function, it could be assumed
      that NFkappaB activation occurs at early stages of inflammation. Potentially,
      NFkappaB could inhibit loss of cardiomyocytes by apoptosis and protect from
      cardiac dilation. Since NFkappaB is a crucial key transcription factor of
      inflammation, its prognostic and future therapeutic relevance should be
      addressed.

PMID- 16297881
TI  - Microtubule-associated protein 8 contains two microtubule binding sites.
AB  - Microtubule-associated proteins (MAPs) are critical regulators of microtubule
      dynamics and functions, and have long been proposed to be essential for many
      cellular events including neuronal morphogenesis and functional maintenance. In
      this study, we report the characterization of a new microtubule-associated
      protein, we named MAP8. The protein of MAP8 is mainly restricted to the nervous
      system postnatally in mouse. Its expression could first be detected as early as
      at embryonic day 10, levels plateau during late embryonic and neonatal periods,
      and subsequently decrease moderately to remain constant into adulthood. In
      addition to its carboxyl terminal binding site, the MAP8 polyprotein also
      contains a functional microtubule-binding domain at its N-terminal segment. The
      association of the carboxyl terminal of the light chain with actin microfilaments
      could also be detected. Our findings define MAP8 as a novel microtubule
      associated protein containing two microtubule binding domains.

PMID- 16297882
TI  - Multiplex real-time PCR for detection of deletions and duplications in dystrophin
      gene.
AB  - Genetic testing of Duchenne and Becker muscular dystrophies (DMD/BMD) is a
      difficult task due to the occurrence of deletions or duplications within
      dystrophin (DMD) gene that requires dose sensitive tests. We developed three
      multiplex quantitative real-time PCR assays for dystrophin exon 5, 45, and 51
      within two major hotspots of deletion/duplication. Each exon was co-amplified
      with a reference X-linked gene and the copy number of the target fragment was
      calculated by comparative threshold cycle method (delta deltaC(t)). We compared
      the performance of this method with previously described end-point PCR
      fluorescent analysis (EPFA) by studying 24 subjects carrying DMD deletions or
      duplications. We showed that Q-PCR is an accurate and sensitive technique for the
      identification of deletions and duplications in DMD/BMD. Q-PCR is a valuable tool
      for independent confirmation of EPFA screening, particularly when
      deletions/duplications of single exons occur or for rapid identification of known
      mutations in at risk carriers.

PMID- 16297883
TI  - Dioscorin isolated from Dioscorea alata activates TLR4-signaling pathways and
      induces cytokine expression in macrophages.
AB  - The Toll-like receptor 4 (TLR4)-signaling pathway is crucial for activating both
      innate and adaptive immunity. TLR4 is a promising molecular target for immune
      modulating drugs, and TLR4 agonists are of therapeutic potential for treating
      immune diseases and cancers. Several medicinal herb-derived components have
      recently been reported to act via TLR4-dependent pathways, suggesting that
      medicinal plants are potential resources for identifying TLR4 activators. We have
      applied a screening procedure to systematically identify herbal constituents that
      activate TLR4. To exclude possible LPS contamination in these plant-derived
      components, a LPS inhibitor, polymyxin B, was added during screening. One of the
      plant components we identified from the screening was dioscorin, the glycoprotein
      isolated from Dioscorea alata. It induced TLR4-downstream cytokine expression in
      bone marrow cells isolated from TLR4-functional C3H/HeN mice but not from TLR4
      defective C3H/HeJ mice. Dioscorin also stimulated multiple signaling molecules
      (NF-kappaB, ERK, JNK, and p38) and induced the expression of cytokines (TNF
      alpha, IL-1beta, and IL-6) in murine RAW 264.7 macrophages. Furthermore, the ERK,
      p38, JNK, and NF-kappaB-mediated pathways are all involved in dioscorin-mediated
      TNF-alpha production. In summary, our results demonstrate that dioscorin is a
      novel TLR4 activator and induces macrophage activation via typical TLR4-signaling
      pathways.

PMID- 16297884
TI  - PKCalpha reduces the lipid kinase activity of the p110alpha/p85alpha PI3K through
      the phosphorylation of the catalytic subunit.
AB  - The modulation of phosphoinositide 3-kinase (PI3K) activity influences the
      quality of cellular responses triggered by various receptor tyrosine kinases.
      Protein kinase C (PKC) has been reported to phosphorylate signalling molecules
      upstream of PI3K and thereby it may affect the activation of PI3K. Here, we
      provide the first evidence for a direct effect of a PKC isoenzyme on the activity
      of PI3K. PKCalpha but not PKCepsilon phosphorylated the catalytic subunit of the
      p110alpha/p85alpha PI3K in vitro in a manner inhibited by the PKC inhibitor
      bisindolylmaleimide I (BIM I). The incubation of PI3K with active PKCalpha
      resulted in a significant decrease in its lipid kinase activity and this effect
      was also attenuated by BIM I. We conclude that PKCalpha is able to modulate
      negatively the lipid kinase activity of the p110alpha/p85alpha PI3K through the
      phosphorylation of the catalytic subunit.

PMID- 16297885
TI  - Purification of a novel arthropod defensin from the American oyster, Crassostrea
      virginica.
AB  - An antimicrobial peptide was purified from acidified gill extract of a bivalve
      mollusk, the American oyster (Crassostrea virginica), by preparative acid-urea-
      polyacrylamide gel electrophoresis and reversed-phase high performance liquid
      chromatography. The 4265.0 Da peptide had 38 amino acids, including 6 cysteines.
      It showed strongest activity against Gram-positive bacteria (Lactococcus lactis
      subsp. lactis and Staphylococcus aureus; minimum effective concentrations [MECs]
      2.4 and 3.0 microg/ml, respectively) but also had significant activity against
      Gram-negative bacteria (Escherichia coli D31 and Vibrio parahemolyticus; MECs 7.6
      and 15.0 microg/ml, respectively). Comparison of the amino acid sequence with
      those of other known antimicrobial peptides revealed that the novel peptide had
      high sequence homology to arthropod defensins, including those from other
      bivalves, the mussels Mytilus edulis and Mytilus galloprovincialis. This is the
      first antimicrobial peptide to be isolated from any oyster species and we have
      named it American oyster defensin (AOD).

PMID- 16297886
TI  - Immunohistochemical localization of gamma and beta subunits of epithelial Na+
      channel in the rat molar tooth pulp.
AB  - The distribution of gamma and beta subunits of epithelial Na(+) channel (ENaC),
      markers for low-threshold mechanoreceptors in peripheral tissues, was examined in
      the tooth pulp. In the root pulp, gammaENaC- and betaENaC-immunoreactive (IR)
      nerve fibers showed a thick smooth appearance. These nerve fibers ascended toward
      the pulp horn and formed subodontoblastic nerve plexuses. Immunoelectron
      microscopic method revealed that 63% of axons were immunoreactive for gammaENaC
      in the root pulp. Virtually all myelinated axons showed gammaENaC-IR (97%),
      whereas unmyelinated axons were mostly devoid of it (12%). These findings suggest
      that myelinated tooth pulp nociceptors respond to mechanical stimuli.

PMID- 16297887
TI  - Cyclic time course of motor excitability modulation during the observation of a
      cyclic hand movement.
AB  - The observation of a sinusoidal flexion-extension of the wrist was utilized to
      determine the continuous time course and phase relation between observed movement
      and its effects on the observer's motor pathways. While observing movements
      performed by others, the observers' cortical motor areas and spinal circuits were
      activated, reflecting the specific temporal and muscular pattern of the actual
      movement (motor resonance). H-reflexes and motor-evoked potentials (MEPs) were
      elicited, respectively, by electrical stimulation of the median nerve and
      magnetic stimulation of the appropriate cortical area, in the right forearm
      muscle Flexor Carpi Radialis (FCR) of subjects who were observing a 1-Hz cyclic
      oscillation of the right prone hand executed by a different person. Observation
      elicited a parallel cyclic excitability modulation of the observer's H-reflex and
      MEP responses with identical period as the observed movement. Modulation was
      phase advanced, as is muscle activation with respect to the real movement. The
      same results were obtained when the observed hand oscillation was executed with
      different frequency (1.6 Hz) and when the hands of mover and observer were
      supine. No motor resonance was elicited by observing the oscillation of a metal
      platform. The excitability modulation of MEPs simultaneously monitored in both
      antagonists of the observer's forearm (FCR and Extensor Carpi Radialis, ECR) was
      in almost perfect phase opposition, reflecting their natural reciprocal
      activation during the execution of a hand oscillation. These findings suggest
      that during observation, motor pathways are modulated subliminally reproducing
      with high temporal fidelity the motor commands needed to execute the observed
      movement.

PMID- 16297888
TI  - Angiotensin II receptors are upregulated by estradiol and progesterone in the
      locus coeruleus, median preoptic nucleus and subfornical organ of ovariectomized
      rats.
AB  - Angiotensin II (Ang II) receptors in specific brain areas and in the anterior
      pituitary are controlled by reproductive hormones. Since Ang II also plays a role
      in controlling reproductive functions, such as luteinizing hormone and prolactin
      secretion, the objective of the present study was to evaluate the regulation of
      Ang II receptors by estradiol (E(2)) and progesterone (P) in areas of the brain
      involved in homeostatic and reproductive functions, such as the locus coeruleus
      (LC), median preoptic nucleus (MnPO) and subfornical organ (SFO). Adult female
      rats were ovariectomized under anesthesia and divided into 2 groups after 2
      weeks: OVX plus E(2)/P replacement (OVXE(2)P) and OVX plus oil vehicle (OVX).
      E(2) was injected for 3 consecutive days followed by an injection of P on the 4th
      day. Animals were killed by decapitation and the brains were removed and frozen.
      Consecutive coronal brain sections were cut in a cryostat and Ang II receptors
      were quantified by autoradiography in the MnPO, LC and SFO. Treatment of OVX rats
      with E(2) and P induced a significant increase in the Ang II receptor binding
      (fmol/mg protein) in the MnPO (OVX: 4.48 +/- 0.58 and OVXE(2)P: 9.89 +/- 1.65),
      LC (OVX: 2.72 +/- 0.37 and OVXE(2)P: 8.03 +/- 0.9) and SFO (OVX: 5.45 +/- 0.66
      and OVXE(2)P: 10.73 +/- 1.79) compared to OVX animals treated with the vehicle, P
      < 0.05. In conclusion, these results show that Ang II receptors are upregulated
      by E(2) and P in the LC, MnPO and SFO of ovariectomized rats.

PMID- 16297889
TI  - Synthesis of C8 alkyl glycosides via palladium-catalyzed telomerization of
      butadiene with O-benzylated aldoses.
AB  - Conditions of the butadiene telomerization with benzylated aldoses with a free
      anomeric hydroxyl, which efficiently furnish the corresponding octadienyl
      compounds have been determined. Deprotection and hydrogenation of the telomers
      over Pd/C led to the octyl glycosides.

PMID- 16297890
TI  - Fractionation, solid-phase immobilization and chemical degradation of long pectin
      oligogalacturonides. Initial steps towards sequencing of oligosaccharides.
AB  - This work presents the optimized separation of pectin oligomers, their analysis
      by matrix-assisted laser desorption/ionization-time of flight mass spectrometry
      (MALDI-TOF MS), their subsequent immobilization to supports, and our initial
      steps towards solid-support assisted sequencing. The ambient pressure strong
      anion-exchange resin Source 15Q combined with ammonium formate buffer (AF) was
      used for the separation of unsaturated and saturated pectic oligogalacturonides
      (OGAs) derived from enzymatic digestion of pectin. Routinely, multi-milligram
      quantities of defined sizes OGAs with DPs from 5 to 19 were produced in excellent
      purity (>95%). Elution of OGAs followed by direct analysis of the peak fractions
      by MALDI-TOF MS. Purified OGAs (DP 5-7) were chemoselectively immobilized onto
      aminooxy-terminated polyethylene glycol polyacrylamide (PEGA) supports. Solid
      phase anchoring took place at the reducing end of the oligosaccharide and
      resulted in the formation of an oxime linkage. The very high coupling yields
      confirmed the general suitability of aminooxy-PEGA resins for the immobilization
      of OGAs of different lengths. The OGA-functionalized PEGA supports were
      subsequently treated with aq TFA at 40 or 60 degrees C, and the chemical
      degradation products released from the support were analyzed by ESIMS. In all
      cases, the original OGA was degraded into smaller oligomers of various sizes down
      to the monomer. This work illustrates some of the basic principles underlying a
      strategy ultimately aimed at solid-support assisted sequencing of
      oligosaccharides.

PMID- 16297891
TI  - Damaged starch characterisation by ultracentrifugation.
AB  - The relative molecular size distributions of a selection of starches (waxy maize,
      pea and maize) that had received differing amounts of damage from ball milling
      (as quantified by susceptibility to alpha-amylase) were compared using analytical
      ultracentrifugation. Starch samples were solubilised in 90% dimethyl sulfoxide,
      and relative size distributions were determined in terms of the apparent
      distribution of sedimentation coefficients g*(s) versus s(20,w). For comparison
      purposes, the sedimentation coefficients were normalised to standard conditions
      of density and viscosity of water at 20 degrees C, and measurements were made
      with a standard starch loading concentration of 8 mg/mL. The modal molecular size
      of the native unmilled alpha-glucans were found to be approximately 50S, 51S and
      79S for the waxy maize, pea and maize amylopectin molecules, respectively, whilst
      the pea and maize amylose modal molecular sizes were approximately 14S and
      approximately 12S, respectively. As the amount of damaged starch increased, the
      amylopectin molecules were eventually fragmented, and several components
      appeared, with the smallest fractions approaching the sedimentation coefficient
      values of amylose. For the waxy maize starch, the 50S material (amylopectin) was
      gradually converted to 14S, and the degradation process included the appearance
      of 24S material. For the pea starch, the situation was more complicated than the
      waxy maize due to the presence of amylose. As the amylopectin molecules (51S)
      were depolymerised by damage within this starch, low-molecular-weight fragments
      added to the proportion of the amylose fraction (14S)--although tending towards
      the high-molecular-weight region of this fraction. As normal maize starch was
      progressively damaged, a greater number of fragments appeared to be generated
      compared to the other two starches. Here, the 79S amylopectin peak (native
      starch) was gradually converted into 61 and 46S material and eventually to 11S
      material with a molecular size comparable to amylose. Amylose did not appear to
      be degraded, implying that all the damage was focused on the amylopectin fraction
      in all three cases. Specific differences in the damage profiles for the pea and
      maize starches may reflect the effect of lipid-complexed amylose in the maize
      starch.

PMID- 16297892
TI  - Flavonoid triglycosides from the seeds of Syzygium aromaticum.
AB  - Two new apigenin triglycosides, apigenin 6-C-[beta-D-xylopyranosyl-(1'''-->2'')
      beta-D-galactopyranoside]-7-O-beta-D-glucopyranoside and apigenin 6-C-[beta-D
      xylopyranosyl-(1'''-->2'')-beta-D-galactopyranoside]-7-O-beta-D-(6-O-p
      coumarylglucopyranoside) were isolated from the ethanol extract of the seeds of
      Syzygium aromaticum. Their structures were elucidated by chemical and spectral
      analysis (UV, FABMS, 1H, 13C NMR, HMQC, HMBC, NOESY and DEPT).

PMID- 16297893
TI  - Computer simulation studies of microcrystalline cellulose Ibeta.
AB  - Molecular mechanics (MM) simulations have been used to model two small crystals
      of cellulose Ibeta surrounded by water. These small crystals contained six
      different extended surfaces: (110), (11 0), two types of (100), and two types of
      (010). Significant changes took place in the crystal structures. In both crystals
      there was an expansion of the unit cell, and a change in the gamma angle to
      almost orthogonal. Both microcrystals developed a right-hand twist of about 1.5
      degrees per cellobiose unit, similar to the twisting of beta-sheets in proteins.
      In addition, in every other layer, made up of the unit cell center chains, a tilt
      of the sugar rings of 14.8 degrees developed relative to the crystal plane as a
      result of a transition of the primary alcohol groups in these layers away from
      the starting TG conformation to GG. In this conformation, these groups made
      interlayer hydrogen bonds to the origin chains above and below. No change in the
      primary alcohol conformations or hydrogen-bonding patterns in the origin chain
      layers was observed. Strong localization of the adjacent water was found for
      molecules in the first hydration layer of the surfaces, due to both hydrogen
      bonding to the hydroxyl groups of the sugar molecules and also due to hydrophobic
      hydration of the extensive regions of nonpolar surface resulting from the axial
      aliphatic hydrogen atoms of the 'tops' of the glucose monomers. Significant
      structuring of the water was found to extend far out into the solution. It is
      hypothesized that the structured layers of water might present a barrier to the
      approach of cellulase enzymes toward the cellulose surfaces in enzyme-catalyzed
      hydrolysis, and might inhibit the escape of soluble products, contributing to the
      slow rates of hydrolysis observed experimentally. Since the water structuring is
      different for the different surfaces, this might result in slower hydrolysis
      rates for some surfaces compared to others.

PMID- 16297894
TI  - Structural studies of the core region of Aeromonas salmonicida subsp. salmonicida
      lipopolysaccharide.
AB  - The core oligosaccharide structure of the in vivo derived rough phenotype of
      Aeromonas salmonicida subsp. salmonicida was investigated by a combination of
      compositional, methylation, CE-MS and one- and two-dimensional NMR analyses and
      established as the following: [carbohydrate: see text] where R=alpha-D-Galp-(1-
      >4)-beta-D-GalpNAc-(1--> or alpha-D-Galp-(1--> (approx. ratio 4:3). Comparative
      CE-MS analysis of A. salmonicida subsp. salmonicida core oligosaccharides from
      strains A449, 80204-1 and an in vivo rough isolate confirmed that the structure
      of the core oligosaccharide was conserved among different isolates of A.
      salmonicida.

PMID- 16297895
TI  - Full assignment of the 1H and 13C spectra and revision of the O-acetylation site
      of the capsular polysaccharide of Streptococcus pneumoniae Type 33F, a component
      of the current pneumococcal polysaccharide vaccine.
AB  - The structure of the capsular polysaccharide from Streptococcus pneumoniae Type
      33F was originally determined by a combination of chemical methods and limited
      use of NMR spectroscopy [Can. J. Biochem. Cell Biol.1984, 62, 666-677]. We report
      full 1H and 13C assignments and confirm the structure of the saccharide repeat
      unit, but find that the site of O-acetylation is O-2 of the -->5)-beta-D-Galf,
      rather than the -->3)-beta-D-Galf residue. We find that a slightly higher
      percentage of the repeat units are O-acetylated: [carbohydrate: see text].

PMID- 16297896
TI  - Crosslinked chitosan--preparation and characterization.
AB  - Chitosan undergoes radical-induced depolymerization in the presence of potassium
      persulfate at 60 degrees C, leading to extensive crosslinking of the fragmented
      chains on subsequent cooling at 4 degrees C. As a result, a possible
      conformational change leading to higher crystallinity, as evidenced by IR, X-ray
      and 13C NMR was observed.

PMID- 16297897
TI  - Synthesis of beta-hederin and Hederacolchiside A1: triterpenoid saponins bearing
      a unique cytotoxicity-inducing disaccharide moiety.
AB  - A facile synthetic approach toward oleanolic acid glycoside bearing alpha-L
      rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl moiety, a unique oligosaccharide
      that strongly induces antitumor activity of oleanane-type triterpenoid saponins,
      was developed. Based on this approach beta-hederin (oleanolic acid 3-O-alpha-L
      rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside) was efficiently prepared from
      oleanolic acid through stepwise glycosylation in linear eight steps with 52%
      overall yield, while Hederacolchiside A1 (oleanolic acid 3-O-alpha-L
      rhamnopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->4)]-alpha-L
      arabinopyranoside) in linear 13 steps with 20% overall yield.

PMID- 16297898
TI  - Crystal structures and spectroscopic characterization of galactitol complexes of
      trivalent lanthanide and divalent alkaline earth chlorides.
AB  - Crystal structures and FT-IR spectra of metal ion-galactitol (C6H14O6, the ligand
      here abbreviated as L) complexes: 2LaCl3*C6H14O6*10H2O and SrCl2*C6H14O6
      complexes are reported. Crystal data of lanthanide chlorides (La3+, Nd3+, Sm3+,
      Eu3+, Tb3+)-galactitol complexes and alkaline earth chlorides (Ca2+, Sr2+)
      galactitol complexes published earlier are summarized. Unlike other lanthanide
      ion-galactitol complexes (2MCl3*C6H14O6*14H2O), lanthanum ions give rise to two
      different structures: LaCl3*C6H14O6*6H2O (LaL1) and 2LaCl3*C6H14O6*10H2O (LaL2).
      Sr2+-galactitol complexes also crystallized with two structures:
      SrCl2*C6H14O6*4H2O (SrL1) and SrCl2*C6H14O6 (SrL2). These metal ions thus give
      different coordination structures with galactitol. The crystal structures and FT
      IR spectra of lanthanide ion and alkaline earth ion-galactitol complexes were
      integrated to interpret the coordination modes of different metal ions. Similar
      IR spectra demonstrate the same coordination modes of the complexes.

PMID- 16297899
TI  - Role of acetylcholinesterase inhibitors in the regulation of amyloid beta
      precursor protein (AbetaPP) metabolism.
AB  - The events that lead to neurodegeneration in Alzheimer's brains are largely
      unknown and this fact creates a great challenge for the definition of treatments
      that may be resolutive for Alzheimer's disease (AD). The current therapeutic
      option for AD patients is the use of acetylcholinesterase inhibitors (AChEIs),
      which gives a symptomatic relief to some of the clinical manifestations of the
      disease. In addition, several authors investigated whether these drugs can also
      affect one of the major pathogenetic pathway postulated for the disease, that is
      the expression and metabolism of the amyloid precursor protein (AbetaPP). The
      literature suggests that cholinergic activities may be significantly involved in
      the regulation of AbetaPP metabolism, thus the characterisation of these aspects
      of AD pharmacology may allow testing cholinergic drugs in their ability to
      intervene at different levels of the pathogenetic chain, other than to provide a
      replacement therapy for lost neurotransmitters. In this paper we review the
      evidence that these drugs, albeit with different quantitative and qualitative
      effects, can modulate the metabolism and expression of AbetaPP, through mechanism
      that involve either an indirect cholinergic mechanism or effects that do not
      involve the canonical pharmacological activity of AChE inhibitors. We also
      provide preliminary evidence that these molecules may affect a gene expression
      program beyond the classical pharmacological pattern suggesting an insight on
      possible unexplored pathways of intervention in AD.

PMID- 16297900
TI  - A peptide derived from acetylcholinesterase is a pivotal signalling molecule in
      neurodegeneration.
AB  - It is now widely accepted that acetylcholinesterase (AChE) also displays non
      cholinergic functions, completely independent of cholinergic transmission.
      Indeed, AChE has been implicated in a variety of trophic and toxic actions in a
      range of different systems. However, it is still uncertain what part of the AChE
      molecule may be responsible for these actions, and indeed via what receptor.
      Recent work has identified a peptide towards the C-terminus of the AChE molecule
      that appears to have very similar effects to non-cholinergic AChE itself. This
      action is to enhance calcium entry, in acute and chronic preparations across a
      trophic-toxic spectrum, depending on concentration applied and/or duration of
      exposure.

PMID- 16297901
TI  - New friendly tools for users of ESTHER, the database of the alpha/beta-hydrolase
      fold superfamily of proteins.
AB  - The structural alpha/beta-hydrolase fold is characterized by a beta-sheet core of
      five to eight strands connected by alpha-helices to form a alpha/beta/alpha
      sandwich. The superfamily members, exemplified by the cholinesterases, diverged
      from a common ancestor into a number of hydrolytic enzymes displaying a wide
      range of substrate specificities, along with proteins with no recognized
      hydrolytic activity. In the enzymes, the catalytic triad residues are presented
      on loops of which one, the nucleophile elbow, is the most conserved feature of
      the fold. Of the other proteins, which all lack from one to all of the catalytic
      residues, some may simply be 'inactive' enzymes while others have been shown to
      be involved in heterologous surface recognition functions. The ESTHER (for
      esterases, alpha/beta-hydrolase enzymes and relatives) database
      (http://bioweb.ensam.inra.fr.esther) gathers and annotates all the published
      pieces of information (gene and protein sequences; biochemical, pharmacological,
      and structural data) related to the superfamily, and connects them together to
      provide the bases for studying structure-function relationships within the
      superfamily. The most recent developments of the database are presented.

PMID- 16297902
TI  - Goniothalamin induces apoptosis in vascular smooth muscle cells.
AB  - Restenosis represents a major impediment to the success of coronary angioplasty.
      Abnormal proliferation of vascular smooth muscle cells (VSMCs) has been shown to
      be an important process in the pathogenesis of restenosis. A number of agents,
      particularly rapamycin and paclitaxel, have been shown to impact on this process.
      This study was carried out to determine the mechanisms of cytotoxicity of
      goniothalamin (GN) on VSMCs. Results from MTT cytotoxicity assay showed that the
      IC(50) for GN was 4.4 microg/ml (22 microM), which was lower compared to the
      clinically used rapamycin (IC(50) of 25 microg/ml [27.346 microM]). This was
      achieved primarily via apoptosis where up to 25.83 +/- 0.44% of apoptotic cells
      were detected after 72 h treatment with GN. In addition, GN demonstrated similar
      effects as rapamycin in inhibiting VSMCs proliferation using bromodeoxyuridine
      (BrdU) cell proliferation assay after 72 h treatment at IC(50) concentration (p >
      0.05). In order to understand the mechanisms of GN, DNA damage detection using
      comet assay was determined at 2h post-treatment with GN. Our results showed that
      there was a concentration-dependent increase in DNA damage in VSMCs prior to
      cytotoxicity. Moreover, GN effects were comparable to rapamycin. In conclusion,
      our data show that GN initially induces DNA damage which subsequently leads to
      cytotoxicity primarily via apoptosis in VSMCs.

PMID- 16297903
TI  - A proposed stoichiometrical calibration procedure to achieve transferability of D
      dimer measurements and to characterize the performance of different methods.
AB  - BACKGROUND: There is little transferability between D-dimer levels obtained by
      different reagents today. This makes it difficult to compare results from
      different clinical studies. OBJECTIVES: We give a comprehensive proposal for
      calibration of D-dimer assays. All crucial steps and underlying assumptions are
      made explicit. METHODS: The new approach is based on using a set of
      fibrinolysates of patient samples clotted and treated with tPA to obtain maximal
      conversion to D-dimers. Their expected maximal D-dimer concentrations are
      calculated stoichiometrically from their different fibrinogen values and the
      published molecular masses of fibrinogen and average D-dimer. The characteristics
      of five latex enhanced D-dimer immunoassays were also tested against early and
      late fibrin fragments using this procedure. These were produced by prolonged
      fibrinolysis of a set of patient samples of varying fibrinogen concentrations.
      RESULTS: These varied typically between methods and lysis times. One of the
      methods showing the highest yield irrespective of lysis time was used for
      calibration. A linear standard curve with zero intercept and R2 = 0.95 was
      obtained. CONCLUSION: Following this procedure will allow better transferability
      of D-dimer in future clinical trails.

PMID- 16297904
TI  - Calcineurin function is required for myofilament formation and troponin I isoform
      transition in Drosophila indirect flight muscle.
AB  - Mutations in the Drosophila calcineurin B2 gene cause the collapse of indirect
      flight muscles during mid stages of pupal development. Examination of cell fate
      specific markers indicates that unlike mutations in genes such as vestigial,
      calcineurin B2 does not cause a shift in cell fate from indirect flight muscle to
      direct flight muscle. Genetic and molecular analyses indicate a severe reduction
      of myosin heavy chain gene expression in calcineurin B2 mutants, which accounts
      at least in part for the muscle collapse. Myofibrils in calcineurin B2 mutants
      display a variety of phenotypes, ranging from normal to a lack of sarcomeric
      structure. Calcineurin B2 also plays a role in the transition to an adult
      specific isoform of troponin I during the late pupal stages, although the
      incompleteness of this transition in calcineurin B2 mutants does not contribute
      to the phenotype of muscle collapse. Together, these findings suggest a molecular
      basis for the indirect flight muscle hypercontractility phenotype observed in
      flies mutant for Drosophila calcineurin B2.

PMID- 16297905
TI  - Analgesic effects of morphine and loperamide in the rat formalin test:
      interactions with NMDA receptor antagonists.
AB  - To reveal peripheral components of opiate analgesia, effects of loperamide,
      opioid agonist which does not penetrate the blood-brain barrier, were examined in
      formalin and acute thermal pain tests in comparison with morphine. Formalin
      administration induces pain behaviour such licking/biting of injected paw
      expressed as two phases. The first phase is caused by C-fibre activation due to
      peripheral stimulation, the second phase attributed to ongoing input from
      peripheral site, leading to spinal hyperexcitability, which is dependent on N
      methyl-D-aspartate (NMDA) receptor activation. Loperamide (3-10 mg/kg) and
      morphine (6 mg/kg) reduced formalin-induced nociceptive behaviours and these
      effects were reversed by naloxone methiodide (0.03-10 mg/kg), opioid receptor
      antagonist which poorly penetrates the blood-brain barrier. Loperamide action was
      enhanced only by centrally active NMDA receptor antagonists memantine (3 mg/kg)
      and CGP 37849 (3 mg/kg), but not by NMDA/glycineB receptor antagonists showing
      weak or no central nervous system (CNS) activity. Present results suggest that
      central NMDA receptor blockade may be necessary to enhance analgesia induced
      through peripheral opioid mechanisms in formalin-evoked nociception.

PMID- 16297906
TI  - Okadaic acid increases the phosphorylation state of alpha1A-adrenoceptors and
      induces receptor desensitization.
AB  - Okadaic acid, a protein phosphatase inhibitor, and phorbol myristate acetate, an
      activator of protein kinase C, increased the phosphorylation state of alpha1A
      adrenergic receptors. The effects of these agents were of similar magnitude but
      that of okadaic acid developed more slowly. Wortmannin (inhibitor of
      phosphoinositide 3-kinase), but not staurosporine (inhibitor of protein kinase
      C), abolished the effect of okadaic acid on the alpha1A-adrenoceptor
      phosphorylation state. The effect of phorbol myristate acetate on this parameter
      was blocked by staurosporine and only partially inhibited by wortmannin. Okadaic
      acid markedly increased the co-immunoprecipitation of both the catalytic and
      regulatory subunits of phosphatidylinositol 3-kinase and of Akt/protein kinase B
      with the adrenoceptor and only marginally increases receptor association with
      protein kinase C epsilon. Okadaic acid induced desensitization of alpha1A
      adrenoceptors as evidenced by a decreased ability of noradrenaline to increase
      intracellular calcium. Such desensitization was fully reverted by wortmannin. Our
      data indicate that inhibition of serine/threonine protein phosphatases increases
      the phosphorylation state of alpha1A-adrenergic receptor and alters the
      adrenoceptor function.

PMID- 16297907
TI  - S100A8 and S100A9 activate MAP kinase and NF-kappaB signaling pathways and
      trigger translocation of RAGE in human prostate cancer cells.
AB  - S100 proteins, a multigenic family of calcium-binding proteins, have been linked
      to human pathologies in recent years. Deregulated expression of S100 proteins,
      including S100A8 and S100A9, was reported in association with neoplastic
      disorders. In a previous study, we identified enhanced expression of S100A8 and
      S100A9 in human prostate cancer. To investigate potential functional implications
      of S100A8 and S100A9 in prostate cancer, we examined the influence of over
      expressed and of purified recombinant S100A8 and S100A9 proteins in different
      prostate epithelial cell lines. S100A8 and S100A9 were secreted by prostate
      cancer cells, a finding which prompted us to analyze a possible function as
      extracellular ligands. S100A8/A9 induced the activation of NF-kappaB and an
      increased phosphorylation of p38 and p44/42 MAP kinases. In addition,
      extracellular S100A8/A9 stimulated migration of benign prostatic cells in vitro.
      Furthermore, in immunofluorescence experiments, we found a strong speckled co
      localization of intracellular S100A8/A9 with RAGE after stimulating cells with
      recombinant S100A8/A9 protein or by increasing cytosolic Ca2+ levels. In summary,
      our findings show that S100A8 and S100A9 are linked to the activation of
      important features of prostate cancer cells.

PMID- 16297908
TI  - Dopamine-related and caspase-independent apoptosis in dopaminergic neurons
      induced by overexpression of human wild type or mutant alpha-synuclein.
AB  - Human wild type (WT) and mutant alpha-synuclein (alpha-syn) genes were
      overexpressed using a Tet-on expression system in stably transfected dopaminergic
      MN9D cells. Their overexpression induced caspase-independent and dopamine-related
      apoptosis not rescued by general caspase inhibitor Z-VAD-FMK. While apoptosis due
      to overexpression of WT alpha-syn was completely abrogated by a specific tyrosine
      hydroxylase (TH) inhibitor, alpha-methyl-p-tyrosine (alpha-MT), the inhibitor
      only partially rescued apoptosis caused by overexpression of alpha-syn mutants.
      In addition, overexpression of mutants enhanced the toxicity of 1-methyl-4
      phenylpyridinium (MPP+) and 6-hydroxyldopamine (6-OHDA) to MN9D cells, whereas
      overexpression of WT protected MN9D cells against MPP+ toxicity, but not against
      6-OHDA. We conclude that WT alpha-syn is beneficial to dopaminergic neurons but
      its overexpression in the presence of endogenous dopamine makes it a potential
      threat to the cells. In contrast, mutant alpha-syn not only caused the loss of WT
      protective function but also the gain-of-toxicity which becomes more serious in
      the presence of dopamine and neurotoxins.

PMID- 16297909
TI  - UV filters in the lens of the thirteen lined ground squirrel (Spermophilus
      tridecemlineatus).
AB  - Major UV filters have been identified in the lens of the 13 lined ground squirrel
      (Spermophilus tridecemlineatus). These were found to be N-acetyl-3
      hydroxykynurenine and N-acetyl-kynurenine, in addition to a small quantity of 3
      hydroxykynurenine. The level of N-acetyl-3-hydroxykynurenine measured in the
      ground squirrel lens, 8.2mM, is approximately 11 times the concentration of 3
      hyroxykynurenine glucoside reported previously for the human lens. Two additional
      UV filters of related structure were also present; however, their structures are
      still under investigation. HPLC elution profiles indicated that the ground
      squirrel lens cortex and nucleus contained comparable amounts of alpha-, beta(H)
      , beta(L)-, and gamma-crystallins. Levels of GSH in the cortex and nucleus were
      12.4 and 7.4mM, respectively. Such high concentrations of GSH may act to inhibit
      oxidation of the 3-hydroxykynurenine and N-acetyl-3-hydroxykynurenine. N
      Acetylated kynurenines are less labile than those with free alpha-amino groups
      since N-acetyl-alpha-amino groups do not undergo spontaneous deamination. This
      modification thus stabilises the squirrel UV filters. In addition, because
      deamination is prevented, the decomposition products will not be involved in
      binding to lens proteins. Because of the similarity of the UV filters present in
      the ground squirrel to those in man, this species may be a suitable animal model
      for investigating the effects of UV radiation on cataract, and other ocular
      diseases, thought to involve exposure to light.

PMID- 16297910
TI  - Melanin in the trabecular meshwork is associated with age, POAG but not
      Latanoprost treatment. A masked morphometric study.
AB  - We wished to conduct a light and electron microscopic investigation of
      pigmentation within the trabecular meshwork of normals and primary open angle
      glaucoma (POAG) patients. In particular we wished to get a precise determination
      of whether there was a relationship between pigmentation and age. In addition we
      wanted to know if there was a difference between normals and POAGs and whether
      trabecular meshwork hyperpigmentation was associated with topical latanoprost
      medication. A total of 25 sham trabeculectomies conducted on post mortem donor
      eyes provided the age-matched normals and there were 62 trabeculectomy specimens
      from POAG patients. These were masked and the meshwork subjected to qualitative
      and quantitative morphological investigation. Light and electron microscopy
      confirmed that most of the trabecular meshwork melanin was phagocytosed and
      within meshwork cells. The granules were measured and found to be of the large
      iris epithelial type. Light microscopic morphometric analysis showed that the
      number of meshwork cell profiles that contained melanin increased both in normals
      and POAGs with age. However there was nearly three times more pigmented meshwork
      cells in the POAGs than the normals. The POAGs were divided into three groups of
      (1) minimal or no medication prior to surgery, (2) maximal medical therapy and
      (3) maximum medical therapy including latanoprost (12 specimens). All groups were
      significantly greater that the normals but of the three it was the maximal
      medical therapy group (without latanoprost) that had the highest pigmentation. We
      concluded that pigmentation of the meshwork is age-related and it is elevated in
      POAG by mechanisms unknown. The melanin accumulation seems to be partly due to
      the disease process, partly as a consequence of chronic antiglaucoma medication
      but interestingly not due to latanoprost even in patients where there is iris
      darkening (four specimens).

PMID- 16297911
TI  - Temperature sensitive secretion of mutant myocilins.
AB  - Recent studies have demonstrated that glaucoma-causing mutant myocilin proteins
      are misfolded and retained in the endoplasmic reticulum of cells. We showed
      previously that P370L mutant myocilin is poorly secreted at 37 degrees C and
      prolonged expression of the protein in differentiated human trabecular meshwork
      cells results in abnormal morphology and cell killing. Culturing cells at a lower
      temperature, a condition known to facilitate protein folding, enhances secretion
      and reverses the cytotoxic effects. We wanted to determine if temperature
      sensitive secretion is a general property of myocilin missense mutants. Wild-type
      or mutant forms of myocilin were transiently expressed in HEK 293 cells cultured
      at either 37 or 30 degrees C and protein secretion was assessed by
      immunoblotting. Of 15 myocilin missense mutants tested, representing a range in
      severity of associated glaucoma phenotypes, 14 displayed increased secretion at
      30 degrees C. The sole exception was K423E, which is associated with an unusual
      mode of glaucoma inheritance. Generally, there is an inverse relationship between
      the degree of mutant myocilin secretion at 30 degrees C and the severity of the
      associated glaucoma phenotype. Mutants that show abundant secretion at 30 degrees
      C such as T377M, G364V, I499F and D380A are associated with less virulent
      glaucoma phenotypes, while mutants such as P370L, I477N, and Y437H display little
      secretion at 30 degrees C and are associated with more virulent glaucoma
      phenotypes. We conclude that temperature sensitive secretion is a property of
      most olfactomedin-domain myocilin mutants. The correlation between temperature
      sensitive secretion and glaucoma phenotype likely reflects the intrinsic
      susceptibility to misfolding of individual mutant proteins. These results support
      the hypothesis that myocilin-induced glaucoma is a protein conformational
      disease. Facilitating mutant protein folding could be a new approach to
      development of therapies for this disease.

PMID- 16297912
TI  - Focus on molecules: cochlin.

PMID- 16297913
TI  - Administration of the immunophilin ligand FK506 differentially attenuates
      neurofilament compaction and impaired axonal transport in injured axons following
      diffuse traumatic brain injury.
AB  - Traumatic axonal injury (TAI) following traumatic brain injury (TBI) remains a
      clinical problem for which no effective treatment exists. TAI was thought to
      involve intraaxonal changes that universally led to impaired axonal transport
      (IAT), disconnection and axonal bulb formation. However, recent,
      immunocytochemical studies employing antibodies to amyloid precursor protein
      (APP), a marker of IAT and antibodies to neurofilament compaction (NFC), RM014,
      demonstrated that NFC typically occurs independent of IAT, indicating the
      existence of different populations of damaged axons. FK506 administration has
      been shown to attenuate IAT. However, in light of the above, the ability of FK506
      to attenuate axonal damage demonstrating NFC requires evaluation. The current
      study explored the potential of FK506 to attenuate both populations of damaged
      axons. Rats were administered FK506 (3 mg/kg) or vehicle 30 min preinjury. Three
      hours post-TBI, tissue was prepared for the visualization of TAI using antibodies
      targeting IAT (APP) or NFC (RMO14) or a combined labeling strategy. Confirming
      previous reports, FK506 treatment reduced the number of axons demonstrating IAT
      in the CSpT, from 411 +/- 54.70 to 91.00 +/- 33.87 (P <or= 0.05) and in the ML
      from 78.62 +/- 16.87 to 41.00 +/- 5.80 (P <or= 0.05). FK506 treatment failed to
      reduce the number of axons demonstrating NFC in either the CSpT or ML. FK506's
      failure to attenuate NFC suggests that additional therapeutic agents may be
      necessary to blunt the full burden of TAI. Because FK506 targets IAT, calcineurin
      appears to be a major target for neuroprotection in damaged axons demonstrating
      IAT.

PMID- 16297914
TI  - Assessment of pain as an emotion in animals and in humans.

PMID- 16297915
TI  - Transplantation of glial-committed progenitor cells into a viral model of
      multiple sclerosis induces remyelination in the absence of an attenuated
      inflammatory response.
AB  - Transplantation of remyelination-competent cells represents a promising strategy
      for the treatment of demyelinating diseases. As the environment dictates the
      success or failure of remyelination, it is critical to understand the role that
      the immune system plays in transplant-mediated remyelination. In this study, we
      evaluated the severity of neuroinflammation following transplantation of glial
      committed progenitor cells into the spinal cords of mice chronically infected
      with mouse hepatitis virus (MHV), a model in which T cells and macrophages are
      critical in amplifying the severity of demyelination. Transplantation was
      performed following viral persistence in which inflammation and demyelination are
      established and clinical disease is evident. Mice were sacrificed 10 and 21 days
      following progenitor cell transplantation and the effect on neuroinflammation
      evaluated. Treatment did not alter accumulation of T cells or macrophages within
      the CNS as compared to control mice. Moreover, progenitor cell implantation did
      not affect local cytokine/chemokine gene expression in the CNS. Finally,
      remyelination associated with transplantation did not result in an imbalance of
      T(H)1-associated cytokine production by virus-specific T cells. These studies
      demonstrate that progenitor cell-mediated remyelination is not the result of
      modulating the composition of the cellular infiltrate nor cytokine expression by
      virus-specific T cells and suggest that remyelination may not depend on
      amelioration of the inflammatory response or alteration of cytokine secretion by
      virus-specific T cells.

PMID- 16297916
TI  - Escherichia coli verotoxin 1 mediates apoptosis in human HCT116 colon cancer
      cells by inducing overexpression of the GADD family of genes and S phase arrest.
AB  - The Escherichia coli verotoxin 1 (VT1) inhibits protein synthesis, cell
      proliferation, and damages endothelial cell in the hemolytic uremic syndrome. VT1
      can specifically bind and act on endothelial cells as well as on many tumor cells
      because these cells express its high affinity receptor, globotriaosylceramide.
      This indicates that VT1 may have both antiangiogenic and antineoplastic
      activities. We investigated this potential of VT1 by incubating several colon
      cancer cell lines with VT1 for different time periods and found that HCT116 cells
      were especially sensitive to VT1. A combination of morphological studies, flow
      cytometry, DNA laddering and annexin V staining confirmed that VT1 irreversibly
      arrests these cells in S phase within 24 h and prolonged incubation triggers DNA
      fragmentation. Concomitant to the activation of the S phase checkpoint, increased
      levels of mRNA and proteins of growth arrest and DNA damage-inducible gene family
      that include GADD34, GADD45alpha, and GADD45beta was observed. Interestingly, no
      significant changes in expression of key cell cycle related proteins such as
      cdk2, cdk4, p21, p27, and p53 was found during the S phase arrest and apoptosis.
      We therefore suggest that GADD proteins might play an important role in VT1
      induced S phase arrest and programmed cell death in HCT116 cells.

PMID- 16297917
TI  - Phosphorylation of Thr695 and Thr850 on the myosin phosphatase target subunit:
      inhibitory effects and occurrence in A7r5 cells.
AB  - Major sites for Rho-kinase on the myosin phosphatase target subunit (MYPT1) are
      Thr695 and Thr850. Phosphorylation of Thr695 inhibits phosphatase activity but
      the role of phosphorylation at Thr850 is not clear and is evaluated here.
      Phosphorylation of both Thr695 and Thr850 by Rho-kinase inhibited activity of the
      type 1 phosphatase catalytic subunit. Rates of phosphorylation of the two sites
      were similar and efficacy of inhibition following phosphorylation was equivalent
      for each site. Phosphorylation of each site on MYPT1 was detected in A7r5 cells,
      but Thr850 was preferred by Rho-kinase and Thr695 was phosphorylated by an
      unidentified kinase(s).

PMID- 16297918
TI  - Steroidogenic activities of follicle-stimulating hormone in the ovary of Japanese
      eel, Anguilla japonica.
AB  - To clarify the physiological functions of follicle-stimulating hormone (FSH)
      during oogenesis in Japanese eel, Anguilla japonica, the steroidogenic activities
      of recombinant Japanese eel FSH (rjeFSH) were assessed in the eel ovary. Female
      eel were injected with salmon pituitary homogenate to enhance the ovarian
      development, and the ovaries at different developmental stages were subjected to
      steroidogenic bioassay. These ovaries could be classified into three types
      according to oocyte growth and development of ovarian follicular cells. The type
      A ovary possessed poorly developed follicular cells around pre- or early
      vitellogenic oocytes, and rjeFSH did not induce sex steroid secretion.
      Testosterone (T) secretion was stimulated by rjeFSH in the type-B ovary with
      developed theca cells and undeveloped granulosa cells around early to mid
      vitellogenic oocytes, whereas estradiol-17beta (E2) secretion was not enhanced.
      The rjeFSH stimulated both T and E2 secretion in a dose-dependent manner from the
      type-C ovary with fully developed theca and granulosa cells around mid
      vitellogenic oocytes. Salmon GTH fraction (sGTH) and a membrane permeable cAMP
      analogue, 8-bromo-cAMP (8-Br-cAMP) also enhanced T and E2 secretion from the type
      C ovary. Human chorionic gonadotropin (hCG) similarly enhanced T secretion, but
      failed to stimulate E2 secretion from the type-C ovary, suggesting different
      effects on steroidogenic activities between eel FSH and hCG in eel ovary. There
      was a positive correlation between the oocyte diameter and E2 secretion from eel
      ovaries stimulated by rjeFSH. These results suggest that aromatase activity is
      accelerated by eel FSH in the granulosa cells, which develop following theca cell
      development in this species.

PMID- 16297919
TI  - The effects of adrenalectomy and corticosterone replacement on induction of
      maternal behavior in the virgin female rat.
AB  - Maternal behavior of the sensitized virgin rat is affected by approach-avoidance
      systems as well as by hypothalamic-pituitary-adrenal (HPA) axis, which is also
      activated during stress. The present experiments investigated the effects of
      adrenalectomy and of varying corticosterone concentrations on the onset and
      expression of maternal behavior in sensitized virgin rats. In the first
      experiment, latency to onset of maternal behavior and time spent licking once
      maternal were positively related to endogenous levels of corticosterone. However,
      few rats showed licking. In the second experiment, virgin rats were
      adrenalectomized or given sham surgeries before being sensitized and being given
      0, 25, 100, 300, or 500 microg/mL of corticosterone in their drinking water. In
      the third experiment, virgin rats were adrenalectomized or given sham surgeries
      and given either control or corticosterone time-release pellets after being
      sensitized. Maternal behavior was then tested. Adrenalectomy increased licking in
      the second experiment and time over pups in the third experiment. Corticosterone
      replacement reduced licking in the second experiment and both licking and time
      over pups in the third experiment. In conclusion, exogenous corticosterone had an
      inhibitory effect on the expression of maternal behavior in the sensitized virgin
      rat, unlike the facilitatory effect previously found in the postpartum rat.

PMID- 16297920
TI  - Simultaneous shear and pressure sensor array for assessing pressure and shear at
      foot/ground interface.
AB  - Foot ulceration is a diabetic complication estimated to result in over $1 billion
      worth of medical expenses per year in the United States alone. This multifaceted
      problem involves the response of plantar soft tissue to both external forces
      applied to the epidermis and internal changes such as vascular supply and
      neuropathy. Increasing evidence indicates that a combination of elevated external
      forces (pressure and shear) and altered tissue properties is key to the etiology
      of foot ulcers. The overall goal of this research is to develop a platform-type
      hardware system that will allow a clinician to measure three-dimensional stress
      tensors (i.e. pressure and shear patterns) on the plantar surface and identify
      areas of concern. Experimental results have demonstrated that an optical approach
      can provide clear indication of both shear and pressure from 50 to 400 kPa with a
      frequency response of 100 Hz, a stress measurement accuracy of 100 Pa and a
      spatial resolution of 8.0mm. Initial evaluation of the system shows strong
      correlation between (i) applied shear and normal stress loads and (ii) the
      optical phase retardance computed for each stress axis of the polymer-based
      stress-sensing elements. These special sensing elements are designed to minimize
      the need for repeated calibration procedures-an issue that has plagued other
      attempts to develop multisensor shear and pressure systems.

PMID- 16297921
TI  - Analysis of phenolic glycosides and saponins in Primula elatior and Primula veris
      (primula root) by liquid chromatography, evaporative light scattering detection
      and mass spectrometry.
AB  - This paper describes the first liquid chromatographic method suitable for the
      simultaneous determination of bioactive compounds, saponins and phenolic
      glycosides, present in Primula elatior and Primula veris, including the NMR data
      of primulaverin and primeverin. Optimum separations were obtained with a Synergi
      4mum Fusion RP 80A column, using 0.025% TFA in water and 5% acetonitrile in
      methanol as mobile phase. Saponins were detected by evaporative light scattering
      detection (ELSD), whereas the phenolic glycosides were monitored by UV at 210 nm.
      The method was validated for repeatability (sigma(rel) <or=4.5%), precision
      (intra- and inter-day variation <or=5.0%), accuracy (recovery >or=97.1%) and
      sensitivity (LOD <or=22 ng (UV) and <or=38 ng (ELSD) on-column, respectively). LC
      MS experiments in negative APCI mode allowed a final peak assignment. Both
      Primula species could easily be differentiated by their saponin pattern. The
      total saponin content was highest in P. veris roots (max. 14.9%), the aerial
      parts or P. elatior contained significantly less amounts; primeverin (0.64-1.42%)
      showed to be the most dominant phenolic glycoside.

PMID- 16297922
TI  - Characterization of volatile organic compounds and odorants associated with swine
      barn particulate matter using solid-phase microextraction and gas chromatography
      mass spectrometry-olfactometry.
AB  - Swine operations can affect air quality by emissions of odor, volatile organic
      compounds (VOCs) and other gases, and particulate matter (PM). Particulate matter
      has been proposed to be an important pathway for carrying odor. However, little
      is known about the odor-VOCs-PM interactions. In this research, continuous PM
      sampling was conducted simultaneously with three collocated TEOM 1400a analyzers
      inside a 1000-head swine finish barn located in central Iowa. Each TEOM was
      fitted with total suspended particulate (TSP), PM-10, PM-2.5 and PM-1
      preseparators. Used filters were stored in 40 mL vials and transported to the
      laboratory. VOCs adsorbed/absorbed to dust were allowed to equilibrate with vial
      headspace. Solid-phase microextraction (SPME) Carboxen/polydimethylsiloxane
      (PDMS) 85 microm fibers were used to extract VOCs. Simultaneous chemical and
      olfactometry analyses of VOCs and odor associated with swine PM were completed
      using a gas chromatography-mass spectrometry-olfactometry (GC-MS-O) system. Fifty
      VOCs categorized into nine chemical function groups were identified and confirmed
      with standards. Five of them are classified as hazardous air pollutants. VOCs
      were characterized with a wide range of molecular weight, boiling points, vapor
      pressures, water solubilities, odor detection thresholds, and atmospheric
      reactivities. All characteristic swine VOCs and odorants were present in PM and
      their abundance was proportional to PM size. However, the majority of VOCs and
      characteristic swine odorants were preferentially bound to smaller-size PM. The
      findings indicate that a significant fraction of swine odor can be carried by PM.
      Research of the effects of PM control on swine odor mitigation is warranted.

PMID- 16297923
TI  - Accurate and rapid estimation of adsorption isotherms in liquid chromatography
      using the inverse method on plateaus.
AB  - The inverse method (IM) is an attractive approach for estimating adsorption
      isotherm parameters in liquid chromatography (LC), mainly due to its experimental
      simplicity and low sample consumption. This article presents a new experimental
      approach, the inverse method on plateaus (IMP), which uses elution profiles on
      concentration plateaus together with IM. This approach enabled us to obtain very
      accurate adsorption isotherms that agreed well with those estimated by means of
      frontal analysis over the entire concentration range under consideration. IMP is
      recommended when accurate adsorption isotherm estimates are required, and
      standard IM is insufficient.

PMID- 16297924
TI  - Development and validation of a solid phase micro-extraction-gas chromatography
      mass spectrometry method for the determination of furan in baby-food.
AB  - An efficient and simple method for the determination of furan in baby-food
      (vegetables and fruits) by solid phase micro-extraction-gas chromatography-mass
      spectrometry (SPME-GC-MS) was developed and validated. Experimental design was
      used to investigate the effects of temperature and time of extraction. The
      calculated regression model was used to find the experimental conditions
      providing the optimal SPME extraction yield. Validation was carried out in terms
      of limit of detection (LOD), limit of quantitation (LOQ), linearity, precision
      and trueness. LOD and LOQ values in the low ngkg(-1) were achieved, whereas
      linearity was established over two order of magnitude. Good precision was
      obtained both in terms of intra-day repeatability and between-day precision on
      two concentration levels (RSD% lower than 3.6%). Recovery values of 91.5+/-6.2%
      and of 96.1+/-1.3% (n=3) were calculated at 75 ngkg(-1) and 75 microgkg(-1)
      level. Finally, the applicability of the method to the determination of furan in
      a number of commercial and home-made baby-food samples was demonstrated.

PMID- 16297925
TI  - Development and characterization of an immobilized enzyme reactor (IMER) based on
      human glyceraldehyde-3-phosphate dehydrogenase for on-line enzymatic studies.
AB  - Immobilized enzyme reactors (IMERs) for on-line enzymatic studies are useful tool
      to select specific inhibitors and may be used for direct determination of drug
      receptor binding interactions and for the rapid on-line screening to identify
      specific inhibitors. This technique has been shown to increase the stability of
      enzymes. The enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an
      important role in the life cycle of the Trypanosoma cruzi and it has become a key
      target in the drug discovery program for Chagas' disease. Crystallographic
      studies have indicated that there are significant inter-species differences in
      GAPDH activity and sensitivity. For example the active sites of GAPDH in T. cruzi
      and humans differ by a substitution of ASP(210) (T. cruzi) by Leu(194) in human.
      Based on this information we initiated the study to develop optimal conditions
      for the covalent immobilization of the human GAPDH enzyme on a modified capillary
      support (400 mm x 0.10 mm). The chromatographic separation of NAD from NADH was
      achieved using a RP-Spherex-diol-OH (10 cm x 0.46 cm, 10 microm, 100 A) column.
      By using multidimensional HPLC chromatography system it was possible to
      investigate the activity and kinetic parameters of the GAPDH-IMER. The values
      obtained for D-GA3P and NAD were K(m)=3.5+/-0.2 mM and 0.75+/-0.04 mM,
      respectively, and were compared with values obtained with the free enzyme. The
      activity of the immobilized GAPDH has been preserved for over 120 days.

PMID- 16297926
TI  - Reversed-phase liquid chromatography/mass spectrometry analysis of reduced
      monoclonal antibodies in pharmaceutics.
AB  - A reversed-phase LC/MS method was developed for reduced antibodies that provides
      efficient separation of light chain and two variants of heavy chain containing N
      terminal glutamine and pyroglutamic acid. The best separation was achieved on
      Zorbax CN and Varian Pursuit DiPhenyl columns eluted with increasing percentage
      of n-propanol and acetonitrile in 0.1% trifluoroacetic acid. Although glutamine
      was genetically coded for the N-terminal residue of heavy chain of a monoclonal
      antibody used in this study, we found that most of it (70%) was converted to
      pyroglutamate during production. The conversion process continued in vitro and
      was monitored by the method. Deconvoluted electrospray ionization mass spectrum
      of the heavy chain revealed the glycosylation profile of a single N-linked sugar
      including a-, mono-, and di-galactosylated biantennary glycans and a 5-mannose
      sugar form.

PMID- 16297928
TI  - Modification of active and porous sublayers of aged polyamide/polysulfone
      composite membranes due to HNO3 treatment: effect of treatment time.
AB  - Changes in electrical and transport parameters for aged composite
      polyamide/polysulfone membrane samples (PAC) and their porous support layers
      (PSU) as a result of chemical treatment (immersion in 1 M HNO3 solution) at four
      different times (12 h < or = t < or = 72 h) have been obtained. Salt
      permeability, ion transport number, and membrane electrical resistance for the
      treated samples were determined from salt diffusion, membrane potential, and
      impedance spectroscopy measurements, which were carried out with the membranes in
      contact with NaCl solutions at different concentrations and compared with those
      determined for fresh and aged nontreated samples. Results show the strong effect
      of aging on membrane parameters, particularly the decrease in salt permeability
      (P(s)) and the increase in membrane electrical resistance (R(m)), while ion
      transport number is hardly affected by aging, chemical treatment, or treatment
      time. Results show how the compaction of the porous structure causes by aging
      (dried membrane matrix structure) can be partially reduced by HNO3 treatment, and
      they also allow the estimation of 24-h treatment as the optimum time (higher salt
      permeability and lower membrane electrical resistance), mainly for the
      polysulfone support layer. The use of equivalent circuits in the analysis of
      impedance spectroscopy data allows separate estimation of the electrical
      resistance associated with each sublayer of the composite PAC membrane samples.
      On the other hand, chemical changes in the active top layer of the PAC membrane
      (polyamide active layer) were obtained from XPS analysis, which show some
      modifications in the atomic concentration percentages of the polyamide
      characteristic elements as a result of acidic treatment time, which are more
      significant after 72-h acidic immersion.

PMID- 16297927
TI  - Simple fluorimetric liquid chromatographic method for the analysis of undecylenic
      acid and zinc undecylenate in pharmaceutical preparations.
AB  - A simple and selective liquid chromatographic method is described for the
      analysis of undecylenic acid (UA) and zinc undecylenate (ZnUA) in pharmaceutical
      preparations. The method is based on the derivatization of the analytes extracted
      from various samples with 2-(2-naphthoxy)ethyl 2-(piperidino)ethanesulfonate. The
      resulting derivative was analyzed by liquid chromatography with fluorimetric
      detection. The quantitation of the method is in the range of 3.0-50.0 microM UA
      with a detection limit of about 0.3 microM (S/N = 3 with 10 microl injection). We
      found that acetonitrile is a selective solvent for differentially dissolving UA
      from coexisted ZnUA in compound formulation. This results in the specific
      analysis of UA in the presence of ZnUA and simply analyzing the coexisted ZnUA by
      the value of total UA (UA+ZnUA) minus that of UA. Application of the method to
      the analysis of undecylenic acid and zinc undecylenate in ointment, powder and
      solution preparations proved feasible.

PMID- 16297929
TI  - Effect of polyethyleneimine ion on the sorption of a reactive dye onto Leacril
      fabric: electrokinetic properties and surface free energy of the system.
AB  - Data are presented on the kinetics, electrokinetics, and surface free energy in
      the process of adsorption of polyethyleneimine (PEI) as a pretreatment of
      Leacril, later dyed with the reactive dye Remazol Brilliant Blue R (RBBR). The
      electrokinetic potential of Leacril is negative, due probably to the presence of
      sulfonate and sulfate end-group onto Leacril fibers. The zeta potential of
      Leacril decreases in absolute value as a function of NaCl concentration in
      solution, probably because of compression of the electrical double layer. The
      zeta potential of Leacril as a function of the concentration of PEI in solution
      increases because of the adsorption of PEI ions through chemical reaction between
      the sulfonate end-groups of Leacril and the amine groups of PEI. The adsorption
      kinetics shows that an increase in the concentration of PEI, brings about an
      increase in the amount of RBBR adsorbed onto the fiber. This may be an indication
      of the chemical reaction between the reactive groups of the polyelectrolyte and
      dye molecules. The behavior of the surface free energy of the systems involved
      confirms these conclusions.

PMID- 16297930
TI  - Pathogenesis of Helicosporidium sp. (Chlorophyta: Trebouxiophyceae) in
      susceptible noctuid larvae.
AB  - Helicosporidium sp. is a unique, achlorophyllous green alga that has been
      reported to infect various insect orders, including Lepidoptera, Diptera, and
      Coleoptera. The infectious cyst stage is ingested by the host, ruptures in the
      midgut lumen, and releases a filamentous cell. Histopathological examinations
      using larvae of a susceptible noctuid host, Spodoptera exigua, showed both cysts
      and filamentous cells affiliated with the microvillar lining of the midgut
      epithelium. A considerable proportion of the ingested cysts (22-39%) were
      recovered in feces collected 24 h after ingestion. A small number of filamentous
      cells passed the midgut epithelium and entered the hemocoel within 4-24 h after
      cyst ingestion. After 48 h, vegetative cell stages were detected in the
      hemolymph, followed by a 4- to 5-day period of increasing multiplication. Cyst
      differentiation in the colonized hemolymph began 6-7 days after the treatment.

PMID- 16297932
TI  - Fragmentation of replicating chromosomes triggered by uracil in DNA.
AB  - The dut mutants of Escherichia coli fail to hydrolyze dUTP and thus incorporate
      uracil into their DNA, suffering from chromosomal fragmentation. The postulated
      mechanism for the double-strand DNA breaks is clustered uracil excision, which
      requires high density of DNA-uracils. However, we did not find enough uracil
      residues or excision nicks in the DNA of dut mutants to account for clustered
      uracil excision. Using a dut recBC(Ts) mutant of E.coli to inquire into the
      mechanism of uracil-triggered chromosomal fragmentation, we show that this
      fragmentation requires DNA replication and, in turn, inhibits replication of the
      chromosomal terminus. As a result, origin-containing sub-chromosomal fragments
      accumulate in dut recBC conditions, indicating preferential demise of replication
      bubbles. We propose that the basic mechanism of the uracil-triggered chromosomal
      fragmentation is replication fork collapse at uracil-excision nicks. Possible
      explanations for the low level terminus fragmentation are also considered.

PMID- 16297933
TI  - Development of a statewide highway safety data warehouse: Massachusetts data
      warehouse and web-based access.

PMID- 16297931
TI  - Molecular dynamics simulations of the influenza hemagglutinin fusion peptide in
      micelles and bilayers: conformational analysis of peptide and lipids.
AB  - Molecular dynamics simulations of the influenza hemagglutinin fusion peptide in
      two differently sized dodecylphosphocholine micelles and a palmitoyl oleoyl
      phosphatidylcholine bilayer were generated to analyze the influence of the
      environment. Four independent trajectories (5 ns each for the bilayer, and 2 ns
      each for the micelles) were generated for each system. The peptide lies at the
      surface of the micelles, while its N-terminal region inserts deeply in the
      bilayer. This leads to a substantial increase of the solvation and rigidity of
      the peptide in micelles as compared to the bilayer. The average structures,
      nevertheless, are similar in all three systems and agree reasonably with micelle
      based NMR structures. When in the bilayer, the peptide increases the chain gauche
      population and area of adjacent lipids in the same binding leaflet, while it has
      the opposite effect for the nearby lipids of the other leaflet. These changes,
      which occur spontaneously to fill voids and defects, cause a decrease in the
      thickness of the membrane in the neighborhood of the peptide. They would be
      expected to promote positive curvature, as consistent with the formation of the
      convex bulge, or "nipple", in the initial stage of membrane fusion. An extension
      of the classical surfactant theory of Israelachvili based on shapes is proposed
      to introduce the concept of a "dynamically induced shape" of the membrane lipids
      by the peptide.

PMID- 16297934
TI  - Using GIS for law enforcement.

PMID- 16297935
TI  - Approaches to understanding young driver risk taking.

PMID- 16297937
TI  - High levels of homocysteine and low serum paraoxonase 1 arylesterase activity in
      children with autism.
AB  - Autism is a behaviorally defined disorder of unknown etiology that is thought to
      be influenced by genetic and environmental factors. High levels of homocysteine
      and oxidative stress are generally associated with neuropsychiatric disorders.
      The purpose of this study was to compare the level of homocysteine and other
      biomarkers in children with autism to corresponding values in age-matched healthy
      children. We measured total homocysteine (tHcy), vitamin B(12), paraoxonase and
      arylesterase activities of human paraoxonase 1 (PON1) in plasma and glutathione
      peroxidase (GPx) activity in erythrocytes from 21 children: 12 with autism (age:
      8.29 +/- 2.76 years) and 9 controls (age: 8.33 +/- 1.82 years). We found
      statistically significant differences in tHcy levels and in arylesterase activity
      of PON1 in children with autism compared to the control group: 9.83 +/- 2.75 vs.
      7.51 +/- 0.93 micromol/L (P < or =0.01) and 72.57 +/- 11.73 vs. 81.83 +/- 7.39
      kU/L (P < or =0.005). In the autistic group there was a strong negative
      correlation between tHcy and GPx activity and the vitamin B(12) level was low or
      suboptimal. In conclusion, our study shows that in children with autism there are
      higher levels of tHcy, which is negatively correlated with GPx activity, low PON1
      arylesterase activity and suboptimal levels of vitamin B(12).

PMID- 16297936
TI  - The immunoreactivity and activity of adenylate cyclase type I are changed in the
      hippocampal CA1 region after transient forebrain ischemia in gerbils.
AB  - Adenylate cyclase (AC) has a specific sensitivity to Ca2+/calmodulin. AC-I, one
      of the mediator of learning and memory, plays an important role in signal
      transduction underlying learning and memory function. In the present study, we
      found ischemia-related changes of AC-I in the hippocampal CA1 region, but not in
      the CA2/3 region, after 5 min of transient forebrain ischemia in gerbils. In the
      sham-operated group, AC-I immunoreactive neurons were detected in pyramidal and
      non-pyramidal cells in the hippocampus proper. AC-I immunoreactivity was
      significantly increased at 3 h in the CA1 region after ischemic insult.
      Thereafter, AC-I immunoreactivity was gradually decreased. Four days after
      ischemic insult, AC-I-immunoreactive CA1 pyramidal cells in the stratum
      pyramidale were very few due to delayed neuronal death. The results of Western
      blot analysis showed that changes of AC-I protein contents were similar to
      immunohistochemical data after ischemic insult. Gpp(NH)p-dependent AC-I activity
      in hippocampal CA1 region was not changed in all groups, while Ca2+/calmodulin
      dependent AC-I activity in hippocampal CA1 region was significantly decreased 24
      h after ischemia-reperfusion. These results suggest that the decrease of AC-I
      activity may be associated with impairment of neurodevelopment and
      neuroplasticity including learning and memory although the AC-I immunoreactivity
      was maintained 24 h postischemic group compared to that of the sham-operated
      group.

PMID- 16297938
TI  - Rosiglitazone inhibits endothelial proliferation and angiogenesis.
AB  - Rosiglitazone, an insulin sensitizer, is known to offer beneficial effects in
      retarding atherosclerotic vascular diseases. Since proliferation and angiogenesis
      are involved in initiation and plaque instability, two critical steps in the
      cardiovascular events, this study was designed to evaluate the mechanisms of
      rosiglitazone on endothelial proliferation and angiogenesis. Rosiglitazone
      treated human umbilical vein endothelial cells were analyzed for growth rate by
      use of cell number counting, 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium
      bromide assay as well as 3H-thymidine incorporation. Cell cycle analysis was
      detected by flow cytometry and cell cycle-related proteins were measured by
      Western blot. Effects of rosiglitazone on angiogenesis were assessed by vascular
      endothelial growth factor (VEGF)-induced tube formation and wound-healing
      migration. Furthermore, effects of rosiglitazone on actin stress fiber were
      observed under confocal microscopy. Our data showed that rosiglitazone inhibits
      endothelial proliferation in a dose-dependent manner. Rosiglitazone caused
      endothelial arrest at G1 phase via affecting several cell cycle-related proteins
      that led to attenuate phosphorylation of retinoblastoma protein. Rosiglitazone
      markedly decreased VEGF-induced tube formation and endothelial cell migration,
      which might be explained by a disorganization of the actin cytoskeleton. Our data
      suggest that both anti-proliferative and anti-angiogenic activities in
      endothelial cells might account for the greater than expected beneficial effects
      of rosiglitazone for the treatment and prevention of atherosclerosis.

PMID- 16297939
TI  - Benthic primary production during emersion: In situ measurements and potential
      primary production in the Seine Estuary (English Channel, France).
AB  - A two year survey of benthic primary production during periods of emersion was
      performed on two stations of an intertidal mudflat (a muddy-sand station and a
      muddy station) in the Seine Estuary (English Channel, France). The goals of this
      study were to investigate the seasonal variations of metabolism, to estimate
      daily potential primary production variation at the annual scale and to estimate
      the annual potential primary production of the mudflat. Primary production and
      respiration were estimated by in situ measurements of carbon dioxide fluxes.
      Chlorophyll a concentration exhibited a great variability on both locations.
      Gross community production ranged from ca. 0 to 77 mg C m(-2) h(-1) at the muddy
      sand location and from ca. 0 to 122 mg C m(-2) h(-1) at the muddy location.
      Community respiration showed a seasonal trend following temperature variations
      (up to 28.51 mg C m(-2) h(-1) in the muddy-sand and up to 23.40 mg C m(-2) h(-1)
      in the mud). Daily potential primary production was calculated, according to
      seasonal variations of photosynthetic parameters calculated using three
      photosynthesis versus irradiance curves obtained for the muddy location. The
      annual gross community primary production was 135 g C m(-2) yr(-1), leading to a
      low autotrophic annual budget, considering an annual community respiration of 110
      g C m(-2) yr(-1).

PMID- 16297940
TI  - GABA receptor agonists in the medial preoptic area and maternal behavior in
      lactating rats.
AB  - We studied the effects of injecting agonists of the inhibitory neurotransmitter
      gamma-aminobutyric acid (GABA) muscimol (GABA-A receptor agonist) and baclofen
      (GABA-B receptor agonist) in the medial preoptic area (MPOA) and neighboring
      brain regions, the bed nucleus of the stria terminalis (BNST), and lateral
      preoptic area (LPO) on maternal behavior. Lactating female rats were implanted
      with bilateral cannulae in the MPOA/BNST on day 1 postpartum. On day 5, a
      maternal behavior test was conducted in the home cage after females received
      injections of muscimol or baclofen (0, 12.5, 50 or 200 ng per side). On day 7,
      after MPOA/BNST injections, a second maternal behavior test was conducted with
      pups placed at the end of a T-runway projecting from the home cage. Finally,
      after injections on day 9 maternal aggression, olfaction, and locomotor behavior
      were tested. The GABA receptor agonists injected in the MPOA/BNST produced dose
      dependent deficits in all components of maternal behavior, including maternal
      aggression, except licking. Muscimol produced deficits in the active component,
      nest building at lower doses than baclofen, both agonists produced deficits in
      retrieving, while baclofen produced deficits in passive components (hovering and
      crouching over pups) at lower doses than muscimol. Both GABA receptor agonists
      increased locomotor activity and reduced olfactory responsiveness but these were
      only correlated with deficits in retrieving and crouching in baclofen-treated
      females.

PMID- 16297941
TI  - Flavones and isoflavones from the west African Fabaceae Erythrina vogelii.
AB  - The CH(2)Cl(2)/MeOH extract of the stem bark of Erythrina vogelii (Fabaceae) from
      Nigeria has yielded two novel isoflavones, 7,4'-dihydroxy-8-(gamma,gamma
      dimethylallyl)-2''zeta-(4''-hydroxyisopropyl)dihydrofurano[1'',3'':5,6]isoflavone
      (vogelin H) (1) and 7,4'-dihydroxy-8-[(2'''zeta,3'''-dihydroxy-3'''-methyl)butyl]
      2'',2''-dimethyl-3'',4''-dehydropyrano[1'',4'':5,6]isoflavone (vogelin I) (2), a
      novel flavone, 7,4'-dihydroxy-2'',2''-dimethyl-3'',4''
      dehydropyrano[1'',4'':5,6]flavone (vogelin J) (3), and eight known flavonoids.

PMID- 16297942
TI  - Sugar beet (Beta vulgaris) pectins are covalently cross-linked through diferulic
      bridges in the cell wall.
AB  - Arabinan and galactan side chains of sugar beet pectins are esterified by ferulic
      acid residues that can undergo in vivo oxidative reactions to form
      dehydrodiferulates. After acid and enzymatic degradation of sugar beet cell walls
      and fractionation of the solubilized products by hydrophobic interaction
      chromatography, three dehydrodiferulate-rich fractions were isolated. The
      structural identification of the different compounds present in these fractions
      was performed by electrospray-ion trap-mass spectrometry (before and after (18)O
      labeling) and high-performance anion-exchange chromatography. Several compounds
      contained solely Ara (terminal or alpha-1-->5-linked-dimer) and
      dehydrodiferulate. The location of the dehydrodiferulate was assigned in some
      cases to the O-2 and in others to the O-5 of non-reducing Ara residues. One
      compound contained Gal (beta-1-->4-linked-dimer), Ara (alpha-1-->5-linked-dimer)
      and dehydrodiferulate. The location of the dehydrodiferulate was unambiguously
      assigned to the O-2 of the non-reducing Ara residue and O-6 of the non-reducing
      Gal residue. These results provide direct evidence that pectic arabinans and
      galactans are covalently cross-linked (intra- or inter-molecularly) through
      dehydrodiferulates in sugar beet cell walls. Molecular modeling was used to
      compute and structurally characterize the low energy conformations of the
      isolated compounds. Interestingly, the conformations of the dehydrodiferulate
      bridged arabinan and galactan fragments selected from an energetic criterion,
      evidenced very nice agreement with the experimental occurrence of the
      dehydrodiferulated pectins. The present work combines for the first time
      intensive mass spectrometry data and molecular modeling to give structural
      relevance of a molecular cohesion between rhamnogalacturonan fragments.

PMID- 16297943
TI  - The angel of death: reshaping global public health.

PMID- 16297944
TI  - I think I got "That Disease": an interview with a medical student who had
      recovered from SARS in Guangzhou, China.

PMID- 16297945
TI  - Severe acute respiratory syndrome (SARS): reshaping global public health.

PMID- 16297946
TI  - Identifying risk factors for tungiasis and heavy infestation in a resource-poor
      community in northeast Brazil.
AB  - Tungiasis is a neglected parasitic skin disease caused by penetration of female
      sand fleas into the epidermis. The ectoparasitosis is widespread in resource-poor
      communities in South America, the Caribbean and sub-Saharan Africa. To identify
      risk factors for the presence of sand fleas and severe infestation in an endemic
      community, we examined the entire population of a traditional fishing village for
      the presence of embedded sand fleas and determined the number and type of
      lesions. Demographic, behavioural and environmental characteristics of the
      population were assessed using a structured questionnaire. Multivariable analysis
      showed that both occurrence of tungiasis and heavy infestation were significantly
      related to poor housing conditions (odds ratio [OR]=4.7, 95% CI 1.4-15.8), lack
      of health education (OR=4.1, 95% CI 2.0-8.6) and presence of animals on the
      compound (OR=1.9, 95% CI 1.1-3.4). Contrary to common belief, a protective effect
      of frequent use of closed footwear could not be demonstrated. Based on the
      population attributable fractions calculated for the major risk factors
      identified, we conclude that several low-cost interventions would have a
      considerable impact on the occurrence of tungiasis and heavy infestation.

PMID- 16297947
TI  - Neighboring group participation. Part 16. Stereoselective synthesis and receptor
      binding examination of the four stereoisomers of 16-bromomethyl-3,17-estradiols.
AB  - The four possible isomers of 3-benzyloxy-16-hydroxymethylestra-1,3,5(10)-trien-17
      ol (1a-4a) with proven configurations were converted into the corresponding 3
      benzyloxy-16-bromomethylestra-1,3,5(10)-triene-3,17-diols (5e-8e). Depending on
      the reaction conditions the cis isomers of 3-benzyloxy-16-hydroxymethylestra
      1,3,5(10)-trien-17-ol (1a and 2a) were transformed into 3-benzyloxy-16
      bromomethylestra-1,3,5(10)-trien-17-yl acetate (5b and 6b) or 16-bromomethyl-3
      hydroxyestra-1,3,5(10)-trien-17-yl acetate (5c and 6c) on treatment with HBr and
      acetic acid. The mechanism of the process can be interpreted as involving front
      side neighboring group participation. Under similar experimental conditions, the
      trans isomers (3a and 4a) yielded only 3-benzyloxy-16-acetoxymethylestra
      1,3,5(10)-trien-17-yl acetates (3b and 4b) or 16-acetoxymethylestra-1,3,5(10)
      triene-3,17-diyl diacetates (3d and 4d). Both the cis (1a and 2a) and the trans
      (3a, and 4a) isomers were transformed into 16-bromomethylestra-1,3,5(10)-trien-17
      ol (5a-8a) by the Appel reaction on treatment with CBr4/Ph3P. Debenzylation of 5a
      8a was carried out with HBr and acetic acid to yield 5e-8e. The debenzylation
      process in the presence of acetic anhydride produces the diacetates 5d-8d. The
      structures of the compounds were determined by means of MS, 1H NMR and 13C NMR
      spectroscopic methods. Compounds 5c-8c and 5e-8e were tested in a radioligand
      binding assay. Except for the affinity of 7e for the estrogen receptor (Ki=2.55
      nM), the affinities of the eight compounds (5c-8c and 5e-8e) for the estrogen,
      androgen and progesterone receptors are low (Ki > 0.55, 0.52 and 0.21 microM,
      respectively).

PMID- 16297948
TI  - Microarray analysis of thioacetamide-treated type 1 diabetic rats.
AB  - It is well known that diabetes imparts high sensitivity to numerous
      hepatotoxicants. Previously, we have shown that a normally non-lethal dose of
      thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats
      due to inhibited tissue repair allowing progression of liver injury. On the other
      hand, DB rats exposed to 30 mg TA/kg exhibit delayed tissue repair and delayed
      recovery from injury. The objective of this study was to investigate the
      mechanism of impaired tissue repair and progression of liver injury in TA-treated
      DB rats by using cDNA microarray. Gene expression pattern was examined at 0, 6,
      and 12 h after TA challenge, and selected mechanistic leads from microarray
      experiments were confirmed by real-time RT-PCR and further investigated at
      protein level over the time course of 0 to 36 h after TA treatment. Diabetic
      condition itself increased gene expression of proteases and decreased gene
      expression of protease inhibitors. Administration of 300 mg TA/kg to DB rats
      further elevated gene expression of proteases and suppressed gene expression of
      protease inhibitors, explaining progression of liver injury in DB rats after TA
      treatment. Inhibited expression of genes involved in cell division cycle (cyclin
      D1, IGFBP-1, ras, E2F) was observed after exposure of DB rats to 300 mg TA/kg,
      explaining inhibited tissue repair in these rats. On the other hand, DB rats
      receiving 30 mg TA/kg exhibit delayed expression of genes involved in cell
      division cycle, explaining delayed tissue repair in these rats. In conclusion,
      impaired cyclin D1 signaling along with increased proteases and decreased
      protease inhibitors may explain impaired tissue repair that leads to progression
      of liver injury initiated by TA in DB rats.

PMID- 16297949
TI  - Evidence that multiple defects in murine DC-SIGN inhibit a functional interaction
      with pathogens.
AB  - Certain viruses, bacteria, fungi and parasites target dendritic cells through the
      interaction with the cellular attachment factor DC-SIGN, making this C-type
      lectin an attractive target for therapeutic intervention. Studies on DC-SIGN
      function would be greatly aided by the establishment of a mouse model, however,
      it is unclear if the murine (m) homologue of human (h) DC-SIGN also binds to
      pathogens. Here, we investigated the interaction of mDC-SIGN, also termed CIRE,
      with the Ebolavirus glycoprotein (EBOV-GP), a ligand of hDC-SIGN. We found that
      mDC-SIGN neither binds EBOV-GP nor enhances infection by reporterviruses
      pseudotyped with EBOV-GP. Analysis of chimeras between mDC-SIGN and hDC-SIGN
      provided evidence that determinants in the carbohydrate recognition domain and in
      the neck domain of mDC-SIGN inhibit a functional interaction with EBOV-GP.
      Moreover, mDC-SIGN was found be monomeric, suggesting that lack of
      multimerization, which is believed to be required for efficient pathogen
      recognition by hDC-SIGN, might be one factor that prevents binding of mDC-SIGN to
      EBOV-GP. Our results suggest that mDC-SIGN on murine dendritic cells is not an
      adequate model for pathogen interactions with hDC-SIGN.

PMID- 16297950
TI  - Down-regulation of the internal ribosome entry site (IRES)-mediated translation
      of the hepatitis C virus: critical role of binding of the stem-loop IIId domain
      of IRES and the viral core protein.
AB  - In a previous study, we observed that hepatitis C virus (HCV) core protein
      specifically inhibits translation initiated by an HCV internal ribosome entry
      site (IRES). To investigate the mechanism by which down-regulation of HCV
      translation occurs, a series of mutations were introduced into the IRES element,
      as well as the core protein, and their effect on IRES activity examined in this
      study. We found that expression of the core protein inhibits HCV translation
      possibly by binding to a stem-loop IIId domain, particularly a GGG triplet within
      the hairpin loop structure of the domain, within the IRES. Basic-residue clusters
      located at the N-terminus of the core protein have an inhibitory effect on HCV
      translation, and at least one of three known clusters is required for inhibition.
      We propose a model in which competitive binding of the core protein for the IRES
      and 40S ribosomal subunit regulates HCV translation.

PMID- 16297951
TI  - JC virus induces altered patterns of cellular gene expression: interferon
      inducible genes as major transcriptional targets.
AB  - Human polyomavirus JC (JCV) infects 80% of the population worldwide. Primary
      infection, typically occurring during childhood, is asymptomatic in
      immunocompetent individuals and results in lifelong latency and persistent
      infection. However, among the severely immunocompromised, JCV may cause a fatal
      demyelinating disease, progressive multifocal leukoencephalopathy (PML). Virus
      host interactions influencing persistence and pathogenicity are not well
      understood, although significant regulation of JCV activity is thought to occur
      at the level of transcription. Regulation of the JCV early and late promoters
      during the lytic cycle is a complex event that requires participation of both
      viral and cellular factors. We have used cDNA microarray technology to analyze
      global alterations in gene expression in JCV-permissive primary human fetal glial
      cells (PHFG). Expression of more than 400 cellular genes was altered, including
      many that influence cell proliferation, cell communication and interferon (IFN)
      mediated host defense responses. Genes in the latter category included signal
      transducer and activator of transcription 1 (STAT1), interferon stimulating gene
      56 (ISG56), myxovirus resistance 1 (MxA), 2'5'-oligoadenylate synthetase (OAS),
      and cig5. The expression of these genes was further confirmed in JCV-infected
      PHFG cells and the human glioblastoma cell line U87MG to ensure the specificity
      of JCV in inducing this strong antiviral response. Results obtained by real-time
      RT-PCR and Western blot analyses supported the microarray data and provide
      temporal information related to virus-induced changes in the IFN response
      pathway. Our data indicate that the induction of an antiviral response may be one
      of the cellular factors regulating/controlling JCV replication in immunocompetent
      hosts and therefore constraining the development of PML.

PMID- 16297952
TI  - 2Apro is a multifunctional protein that regulates the stability, translation and
      replication of poliovirus RNA.
AB  - Poliovirus 2A(pro) is required for the inhibition of host cell protein synthesis
      and efficient viral replication. We investigated the role of 2A(pro) in
      regulating viral RNA stability, translation and replication in HeLa S10
      reactions. The protease activity of 2A(pro) or its polyprotein precursors, 2AB or
      P2, was required to increase the stability of viral RNA and prolong translation.
      Since other viral proteins were not required for the observed effects of 2A(pro),
      it is likely that a cellular protein(s) modified by 2A(pro) mediated these
      effects on stability and translation. In addition, the protease activity of
      2A(pro) stimulated negative-strand initiation by approximately five-fold but had
      no effect on positive-strand initiation. The 2A(pro) stimulation of negative
      strand synthesis was independent of its effect on stability and translation.
      These findings further extend the previously known functions of protein 2A(pro)
      to include its role in increasing RNA stability, prolonging translation and
      stimulating negative-strand synthesis.

PMID- 16297953
TI  - Identification of DNA-binding sites for the activator involved in late
      transcription of the temperate lactococcal phage TP901-1.
AB  - Alt, encoded by the lactococcal phage TP901-1, is needed for late transcription.
      We identify Alt as a DNA-binding protein, and footprint analysis shows that Alt
      binds to a region containing four imperfect direct repeats (ALT boxes) located 
      76 to -32 relative to the P(late) transcriptional start site. The importance of
      the ALT boxes was confirmed by deletion of one or two ALT boxes and by
      introducing mutations in ALT boxes 1 and 4. Alt is proposed to act as a tetramer
      or higher multimer activating transcription of TP901-1 late genes by binding to
      the four ALT boxes, and bending of the DNA may be important for transcriptional
      activation of P(late). Furthermore, our results suggest that DNA replication may
      be required for late transcription in TP901-1. Additionally, we identify gp28 of
      the related lactococcal phage Tuc2009 as an activator and show that the
      activators required for late transcription in TP901-1 and Tuc2009 are
      interchangeable.

PMID- 16297955
TI  - The genomic RNA packaging scheme of Red clover necrotic mosaic virus.
AB  - Red clover necrotic mosaic virus (RCNMV) is a small icosahedral plant virus with
      a bipartite RNA genome. While the RCNMV genome consists of two RNAs, it has not
      been definitively established whether these RNAs are co-packaged into a single
      virion or packaged individually into separate virions. Biochemical evidence
      exists to support both hypotheses. To determine the genomic RNA complement within
      RCNMV, virions were subjected to heat treatments and UV crosslinking. A stable
      RNA-1:RNA-2 heterodimer was formed with both treatments establishing that RCNMV
      genomic RNAs are co-packaged into a single virion. Furthermore, RNA-2 homodimer
      and homotrimers were also observed indicating that some virions contain multiple
      copies of RNA-2 exclusively. These results indicate that RCNMV virions consist of
      two distinct populations: (i) virions containing both genomic RNAs; and (ii)
      virions with multiple copies of RNA-2. This type of hybrid packaging arrangement
      was unexpected and appears to be unique among the multipartite RNA viruses.

PMID- 16297957
TI  - The effect of hygienic treatment on the microbial flora of biowaste at biogas
      plants.
AB  - In Sweden, full-scale, commercial biogas plants (BGP), which process low-risk
      animal waste, operate a separate pre-pasteurisation at 70 degrees C for 60 min as
      required by EEC regulation 1774/2002. The purpose of this study was to establish
      if, during pasteurisation and further processing and handling in full-scale BGPs,
      pathogens in biowaste could be sufficiently reduced to allow its use on arable
      land. Four BGPs were sampled on six occasions during 1 year. Sampling was
      performed from six locations during biogas production. The samples being analysed
      quantitatively to detect indicator bacteria (Escherichia coli, Enterococcus spp.
      and coliforms) and spore-forming bacteria (Clostridium spp. and Bacillus spp.)
      and qualitatively for bacterial pathogens (salmonella, listeria, campylobacter
      and VTEC O157). Salmonella was the most frequently isolated pathogen before
      pasteurisation In general, the treatment adequatly reduced both indicator and
      pathogenic bacteria. Spore-forming bacteria were not reduced. However,
      recontamination and regrowth of bacteria in biowaste was frequently noted after
      pasteurisation and digestion.

PMID- 16297956
TI  - Numerical study of short-term afterimages and associate properties in foveal
      vision.
AB  - A cellular model of the primate retina has been developed. Unlike existing
      models, it incorporates spatial non-uniformities, such as the random arrangement
      of L and M cones, and the radial dilation with eccentricity. Based on a
      population of ganglion cell activities, colour-image representation is modelled
      with the luminance and the R-G opponent channels. The developed model reproduces
      experimentally known properties in temporal and spatial vision. Furthermore,
      spatio-temporally coupled properties such as transition from positive to negative
      phases in an afterimage, are recapped. In colour vision, the model can explain
      the insensitivity in our colour perception to the L/M cone ratio.

PMID- 16297954
TI  - Phosphorylation of the VP16 transcriptional activator protein during herpes
      simplex virus infection and mutational analysis of putative phosphorylation
      sites.
AB  - VP16 is a virion phosphoprotein of herpes simplex virus and a transcriptional
      activator of the viral immediate-early (IE) genes. We identified four novel VP16
      phosphorylation sites (Ser18, Ser353, Ser411, and Ser452) at late times in
      infection but found no evidence of phosphorylation of Ser375, a residue
      reportedly phosphorylated when VP16 is expressed from a transfected plasmid. A
      virus carrying a Ser375Ala mutation of VP16 was viable in cell culture but with a
      slow growth rate. The association of the mutant VP16 protein with IE gene
      promoters and subsequent IE gene expression was markedly reduced during
      infection, consistent with prior transfection and in vitro results. Surprisingly,
      the association of Oct-1 with IE promoters was also diminished during infection
      by the mutant strain. We propose that Ser375 is important for the interaction of
      VP16 with Oct-1, and that the interaction is required to enable both proteins to
      bind to IE promoters.

PMID- 16297958
TI  - Adsorption of anionic and nonionic surfactant mixtures from synthetic detergents
      on soils.
AB  - Adsorption of anionic surfactant (sodium dodecylbenzenesulfonate, SDBS) and
      nonionic surfactant (an alcohol ethoxylates with 12 carbons and 9 oxyethyl
      groups, A12E9) mixtures, widely used as the major constituents of synthetic
      detergents in China and become the most common pollutants in the environment, on
      soils was conducted to investigate the behavior of mixed surfactants in soils.
      The effects of addition order and mixing ratios of two surfactants, associated
      with pH and ion strength in solutions, on adsorptions were considered. The
      results show that saturated adsorption amount of SDBS and A12E9 on soils
      decreased respectively when A12E9 was added into soils firstly compared with that
      secondly, possibly resulting from the screening of A12E9 to part adsorption sites
      on soils and the hydrocarbon chain-chain interactions between SDBS and A12E9. The
      adsorption of SDBS and A12E9 on soils was enhanced each other at pre-plateau
      region of isotherms. At plateau region of isotherms, the adsorption of SDBS on
      soils decreased with the increase of molar fraction of A12E9 in mixed surfactant
      solutions, while that of A12E9 increased except the molar ratio of SDBS to A12E9
      0.0:1.0. With the increase of pH in mixed surfactant solutions, adsorption amount
      of SDBS and A12E9 on soils decreased, respectively. The reduction of ion strength
      in soils resulted in the decrease of adsorption amount of SDBS and A12E9 on
      soils, respectively.

PMID- 16297959
TI  - Surface-mediated formation of PBDD/Fs from the high-temperature oxidation of 2
      bromophenol on a CuO/silica surface.
AB  - As a model brominated hydrocarbon that may form brominated dioxins, we studied
      the surface-mediated, oxidative thermal degradation of 2-bromophenol on a
      supported copper oxide catalyst in a 1 mm i.d., fused silica flow reactor at a
      constant concentration of 90 ppm over a temperature range from 250 to 550 degrees
      C. Observed products included: dibenzo-p-dioxin (DD), 1-monobromodibenzo-p-dioxin
      (1-MBDD), dibromodibenzo-p-dioxin (DBDD), tribromodibenzo-p-dioxin (TrBDD), 4
      monobromodibenzofuran (4-MBDF), 2,4,6-tribromophenol, 2,4- and 2,6-dibromophenol,
      and polybrominated benzenes. The results are compared and contrasted with
      previous work on surface catalyzed oxidative thermal degradation of 2
      chlorophenol as well as our own work with the surface-catalyzed pyrolytic thermal
      degradation of 2-bromophenol. Typically 20 to 200x higher yields of PBDDs are
      observed for 2-bromophenol than for the analogous PCDDs for 2-chlorophenol.
      However the anticipated PBDF, 4,6-DBDF, was not observed and 4-MBDF was observed
      at very low yields. Surprisingly, the maximum yields of PBDDs were observed at
      higher temperatures than under pyrolytic conditions. This is attributed to
      regeneration of the catalytic surface due to the presence of oxygen. Higher
      yields of polybrominated phenols and polybrominated benzenes were also observed
      than for the analogous chlorinated phenols and benzenes from the oxidation of 2
      chlorophenol. This can be attributed to the ease of bromination over chlorination
      based on the higher abundance of bromine atoms present for 2-bromophenol than
      chlorine atoms present for 2-chlorophenol.

PMID- 16297960
TI  - Enhanced phytoextraction of Pb and other metals from artificially contaminated
      soils through the combined application of EDTA and EDDS.
AB  - Chemically enhanced phytoextraction is achieved by the application of chelates to
      soils. Using pot experiments, the effect of the combined application of EDTA and
      EDDS on the uptake of Cu, Pb, Zn and Cd by Zea mays L. was studied. Among the
      tested application ratios of 1:1, 1:2, and 2:1 (EDTA/EDDS), 2:1 of EDTA:EDDS was
      the most efficient ratio for increasing the concentrations of Cu, Pb, Zn and Cd
      in the shoots. The combined application of 3.33 mmol kg(-1) soil of EDTA+1.67
      mmol kg(-1) soil of EDDS produced 650 mg kg(-1) of Pb in the shoots, which was
      2.4 and 5.9 times the concentration of Pb in the shoots treated with 5 mmol kg(
      1) of EDTA and EDDS alone, respectively. The total phytoextraction of Pb reached
      1710 microg kg(-1) soil, which was 2.1 and 6.1 times the total Pb from 5 mmol kg(
      1) EDTA and EDDS alone, respectively. The combined application of EDTA and EDDS
      also significantly increased the translocation of Pb from the roots to the
      shoots. The mechanism of enhancing the phytoextraction of Pb by the combined
      application of EDTA+EDDS did not involve a change in the pH of the soil. The
      increase in the phytoextraction of Pb by the shoots of Z. mays L. was more
      pronounced than the increase of Pb in the soil solution with the combined
      application of EDTA and EDDS. It was thought that the major role of EDDS might be
      to increase the uptake and translocation of Pb from the roots to the shoots of
      plants.

PMID- 16297961
TI  - Phytochelatins do not correlate with the level of Cd accumulation in
      Chlamydomonas spp.
AB  - Chlamydomonas acidophila KT-1 and Chlamydomonas acidophila DVB238 exhibit a
      strong heavy metal tolerance, but C. acidophila DVB238 can accumulate a much
      higher amount of Cadmium (Cd) than C. acidophila KT-1. Phytochelatins (PCs) are
      known to play an important role in the detoxification of several toxic heavy
      metals, but the relationship between PCs and Cd accumulation is not clear. PC
      metabolism and Cd accumulation were investigated by using three Chlamydomonas
      strains including Chlamydomonas reinhardtii C-9 as a standard alga. The results
      showed that the PC content did not correlate closely with the level of Cd
      accumulation, maintenance of a high GSH level seeming to be more important for Cd
      accumulation. The ultrastructure of C. acidophila KT-1 was extremely disrupted by
      a great increase in starch granules, which resulted in a moribund state, but
      hyper-accumulator C. acidophila DVB238 did not exhibit an increase in starch
      granules in its cells, in spite of Cd accumulation in its chloroplasts, cytosol
      and vacuoles. These results indicated that C. acidophila DVB238 probably has a
      developed detoxification system preventing such as destruction of the cells due
      to Cd toxicity.

PMID- 16297962
TI  - Methods for synthesis of nonabromodiphenyl ethers and a chloro-nonabromodiphenyl
      ether.
AB  - Polybrominated diphenyl ethers (PBDEs) have been used extensively as brominated
      flame retardants (BFRs) in textiles, upholstery and electronics. They are
      ubiquitous contaminants in wildlife and humans. A low concentration of
      nonabrominated diphenyl ethers (nonaBDEs) is present in commercial DecaBDE and
      they are also abiotic and biotic debromination products of decabromodiphenyl
      ether (BDE-209). The objective of the present work was to develop methods for
      synthesis of the three nonaBDEs, 2,2',3,3',4,4',5,5',6-nonabromodiphenyl ether
      (BDE-206), 2,2',3,3',4,4',5,6,6'-nonabromodiphenyl ether (BDE-207) and
      2,2',3,3',4,5,5',6,6'-nonabromodiphenyl ether (BDE-208), with the intention of
      making them available as authentic standards for analytical, toxicological and
      stability studies, as well as studies regarding physical-chemical properties. Two
      methods were developed, one based on perbromination of phenoxyanilines and the
      other via reductive debromination of BDE-209 by sodium borohydride followed by
      chromatographic separation of the three nonaBDE isomers formed. An additional
      nonabrominated compound, 4'-chloro-2,2',3,3',4,5,5',6,6'-nonabromodiphenyl ether
      (Cl-BDE-208), was also synthesized in the present work. Cl-BDE-208, prepared by
      the perbromination of 4-chlorodiphenyl ether, may be used as an internal standard
      in analysis of highly brominated diphenyl ethers. BDE-206, BDE-207, BDE-208 and
      Cl-BDE-208 were characterized by 1H NMR, 13C NMR, electron ionization mass
      spectra and by their melting points. The structures of all three nonaBDEs have
      been characterized previously by X-ray crystallography.

PMID- 16297963
TI  - Removal of insoluble heavy metal sulfides from water.
AB  - The necessity of heavy metal removal from wastewater has led to increasing
      interest in absorbents. We have developed a new approach to obtain high metal
      adsorption capacity by precipitating metal sulfides with sodium sulfide on the
      surface of bentonite and adhere them to the absorbent. This method allowed to
      remove approximately 90% of cadmium as CdS from 10(-4)-10(-6) M CdCl2 solutions.
      Additional reactions are related to the removal of excess sodium sulfide by the
      release of hydrogen sulfide and oxidation to sulfur using carbogen gas (5% CO2,
      95% O2) followed by aeration.

PMID- 16297964
TI  - An experiment in the electrokinetic removal of copper from soil contaminated by
      the brass industry.
AB  - The feasibility of electrokinetic remediation of copper-contaminated soil was
      evaluated following eight days of electroreclamation. The results indicate that
      electrokinetic reclamation of Cu is totally ineffective in soil composed
      primarily of clay minerals and organic matter. The strong absorption of copper by
      this kind of soil, in our view mainly a result of retention by the clay
      component, makes it resistant to mobilization by the electrogenerated acidic
      front as well as by citrates (the competitors of natural chelating agents, i.e.,
      humates). Such conditions, while adverse for the electroremediation process, may
      cause this kind of soil to act as a natural barrier to the leaching of copper
      ions.

PMID- 16297965
TI  - Cadmium exposure from the cement dust emissions: a field study in a rural
      residence.
AB  - The cement dust is one of the causes of pollution in the environment. In the
      present study, the cadmium concentrations of soil and plant specimens taken from
      a rural area exposed to cement factory emissions were determined and also the
      blood concentrations and sensitivity conditions in humans residing in this rural
      area were investigated. The 108 soil (36 for control) and plant specimens were
      collected from eight different directions of the cement plant located in
      Cukurhisar town in Eskisehir city. Blood samples of the individuals residing in
      this area were taken from 258 subjects (258 for control) following a physical
      examination, and patch tests were also applied. The results show that the cadmium
      concentrations of the soil and plant specimens taken from different places in
      different directions of the factory were higher than in the control areas. The
      physical examination of subjects did not reveal results different from those of
      the control group except for the diagnosis of contact dermatitis. The analysis of
      venous blood samples showed that cadmium concentrations were found to be within
      the reference values given for both groups, but higher in the subjects (p<0.001).
      According to the results of patch tests, sensitivity to cadmium was found to be
      more frequent for the subject group than the control group (p<0.05). Those
      results show that, although clinical tools revealed no toxic effects for the
      subject, except contact dermatitis, the cement plant increases cadmium pollution
      on the surrounding environment.

PMID- 16297966
TI  - Arsenic accumulation by two brake ferns growing on an arsenic mine and their
      potential in phytoremediation.
AB  - In an area near an arsenic mine in Hunan Province of south China, soils were
      often found with elevated arsenic levels. A field survey was conducted to
      determine arsenic accumulation in 8 Cretan brake ferns (Pteris cretica) and 16
      Chinese brake ferns (Pteris vittata) growing on these soils. Three factors were
      evaluated: arsenic concentration in above ground parts (fronds), arsenic
      bioaccumulation factor (BF; ratio of arsenic in fronds to soil) and arsenic
      translocation factor (TF; ratio of arsenic in fronds to roots). Arsenic
      concentrations in the fronds of Chinese brake fern were 3-704 mg kg-1, the BFs
      were 0.06-7.43 and the TFs were 0.17-3.98, while those in Cretan brake fern were
      149-694 mg kg-1, 1.34-6.62 and 1.00-2.61, respectively. Our survey showed that
      both ferns were capable of arsenic accumulation under field conditions. With most
      of the arsenic being accumulated in the fronds, these ferns have potential for
      use in phytoremediation of arsenic contaminated soils.

PMID- 16297967
TI  - A 2,000-year record of mercury and ancient civilizations in seal hairs from King
      George Island, West Antarctica.
AB  - The concentrations of total mercury (Hg(T)) and three bio-essential elements
      (phosphor, potassium, sodium) were analyzed in Antarctic seal hairs from a lake
      core spanning the past 2,000 years and collected from King George Island (63
      degrees 23'S, 57 degrees 00'W), West Antarctica. The Hg(T) concentration shows a
      significant fluctuation while the levels of the three bio-essential elements
      remain almost constant. The rise and fall of the Hg(T) concentration in the seal
      hairs are found to be closely coincided with ancient activities of gold and
      silver mining using Hg-amalgamation process around the world, especially in the
      Southern Hemisphere. Briefly, Hg(T) levels are high during five episodes of
      extensive gold and silver mining activities--Rome Empire and China Han Dynasty
      (approximately 18-300 A.D.), Maya period and China Tang (750-900 A.D.), Incas
      civilization and Christian Kingdom (1200-1500 A.D.), New world (1650-1800 A.D.),
      and modern industry period (1840 A.D.-present); they are low during four time
      periods of reduced gold and silver mining activities--the China Han and Rome fall
      (since 300 A.D.), Maya fall and Wartime period in China (1050-1250 A.D.), Pizarro
      coming (ca. 1532 A.D.) and Independence War of South America (1800-1830 A.D.).
      Two profiles of Hg(T) in other two lake cores, one affected by seal excrements
      and the other by penguin droppings, from the same region are similar to the one
      in seal hairs. The Hg concentration profile in the seal hairs is significantly
      correlated with the one in a peat bog of Southern Chile near King George Island.
      Since Hg is existent mainly at the form of methyl-mercury in seal hairs, this
      correlation supports a relationship and link between atmospheric mercury
      concentration and methyl-mercury production. Comparing with samples from American
      and European continents, the Antarctic seal hairs provide an archive of total
      mercury concentration in surface seawater of the South Ocean less affected by
      regional human activities, and this archive may provide a good reference for
      assessing the global Hg emissions, depositions and recycling in the past thousand
      years.

PMID- 16297969
TI  - Proceedings of the 45th International Symposium on Regulation of Enzyme Activity
      and Synthesis in Normal and Neoplastic Tissues. September 27-28, 2004.
      Indianapolis, Indiana, USA.

PMID- 16297970
TI  - Histopathologic behavior of endometrial hyperplasia during tamoxifen therapy for
      breast cancer.
AB  - OBJECTIVE: The purpose of the present study is to prospectively evaluate the
      effects of tamoxifen on the pathological behavior of endometrial hyperplasias
      without atypia, diagnosed before the start of adjuvant endocrine therapy, in
      menopausal patients suffering from breast cancer. METHODS: Twenty-six patients
      suffering from estrogen-receptor positive breast cancer and candidate to receive
      adjuvant tamoxifen, were found to be affected by endometrial hyperplasias before
      the start of endocrine therapy. All women showed a baseline endometrial stripe,
      measured by transvaginal ultrasonography, thicker than 4 mm and the diagnosis of
      endometrial hyperplasia was made by hysteroscopy and endometrial biopsy. Two
      patients showing complex atypical hyperplasia underwent vaginal hysterectomy,
      whereas the remaining 24 patients, suffering from endometrial hyperplasia without
      atypia, were followed on a yearly basis during the period of tamoxifen intake, by
      hysteroscopy and endometrial biopsy. RESULTS: Baseline histopathology showed
      simple and complex hyperplasia in 20 and in 4 patients, respectively. The median
      follow-up period was 38 months; in particular, all patients underwent endometrial
      assessment after 12 months, while 22, 16, 10 and 4 patients were followed-up
      after 24, 36, 48 and 60 months of tamoxifen therapy, respectively. Progression
      from complex hyperplasia to complex atypical hyperplasia (1 patient) and from
      complex and simple hyperplasia to adenocarcinomas (2 patients) was found within
      24 months of tamoxifen intake in 3 patients (12.5%). In 2 patients (8.3%), a
      progression from simple to complex hyperplasia was detected within 36 months of
      tamoxifen treatment. In 13 patients (54.1%), stable histology of simple or
      complex hyperplasia was found, whereas 6 patients (25.0%), with focal hyperplasia
      harbored in an endometrial polyp, showed a normalization of endometrial histology
      after polyp resection. CONCLUSIONS: Endometrial hyperplasias without atypia
      diagnosed before endocrine therapy for breast cancer in menopausal patients show
      an early and high progression-rate to atypical lesions under tamoxifen influence.

PMID- 16297968
TI  - Meteorological and oceanographic conditions in the northern Adriatic Sea during
      the period June 1999-July 2002: influence on the mucilage phenomenon.
AB  - Mucilage events (formation of very large organic aggregates and gelatinous
      surface layers) have been documented several times during the past two centuries
      in the northern Adriatic Sea (NA), while their frequency has significantly
      increased since 1988. In this work, meteorological and oceanographic conditions
      in the NA during the period June 1999-July 2002 are described and their relation
      to the outbreak and fate of the mucilage phenomenon was investigated. Salinity
      and temperature data were collected during approximately monthly cruises along
      three transects in the NA. Relevant meteorological situations (air temperature,
      rainfall, wind) were selected from large-scale ECMWF analyses and from the Local
      Analysis and Prediction System (LAPS; Emilia Romagna Meteorological Service),
      while sea conditions (waves) were analysed by means of the Wave Adriatic Model
      (WAM). Data for air temperature, rainfall, and wind from several meteorological
      stations in the region were used. Average seasonal cycles of sea temperature and
      salinity simulated with statistical models, based on historical data collected in
      the NA since 1972, were used to determine thermal and haline anomalies. The
      monthly anomaly variability of maximum and minimum air temperatures, rainfall
      amount and number of rainy days did not appear to be relevant for the mucilage
      phenomenon outbreak. In contrast, both vertical and horizontal thermohaline
      gradients in the region were more developed during late spring and summer of 2000
      and particularly of 2002, when the mucilage events were of greatest extent in
      space and time, compared to 2001 (short-lived event) and 1999 (no event). These
      more pronounced gradients were due to a combination of several unusual
      conditions: sharp heating of the sea surface in May-June, domination of eastwards
      transport of freshened waters formed in the Po Delta area, and intrusion of very
      high salinity intermediate waters originating in the eastern Mediterranean.
      Moreover, in winter of both 2000 and 2002 very dense and cold water formed and
      remained in the bottom layer until spring, contributing to increase the
      stratification degree of the water column. The duration of the mucilage events
      and their spatial distribution in the region depend strongly on meteorological
      changes. Recurrent anticyclonic conditions, characterized by low wind and calm
      sea, favour extended events in time (up 2 months in 2002). In contrast, highly
      perturbed weather, particularly due to strong "bora" wind, can be determined in
      sharp decay of the event (e.g. in July 2000).

PMID- 16297971
TI  - Influence of oral contraceptives in the development of post-molar trophoblastic
      neoplasia--a systematic review.
AB  - OBJECTIVE: Controversy exists regarding the use of oral contraceptives following
      hydatidiform mole and possible increased risk of persistent trophoblastic
      neoplasia. The purpose of this study is to perform a systematic review of the
      literature to assess the evidence for and against a possible link between oral
      contraceptive use and the need for chemotherapy after molar evacuation. METHODS:
      We searched the computerized databases MEDLINE, EMBASE, Popline, Web of Sciences,
      LILACS and the Cochrane Controlled Trials Register, ISI Proceedings, performed a
      hand search of references and wrote to experts to identify randomized controlled
      trials and observational studies comparing oral contraceptives with other methods
      of contraception. Quality assessment included: concealment of allocation;
      intention to treat analysis; plus attrition bias for trials; confounding factors
      and selection bias for observational studies. We collected or calculated risk
      ratios for the incidence of gestational trophoblastic neoplasia and hCG
      regression time associated with oral contraceptive use. RESULTS: Two randomized
      controlled trials were included for analysis. The risk ratios for OC use were
      similar in both studies: 0.69 (0.12-3.98) and 0.71 (0.46-1.10) respectively. No
      attempt to summarize these results was made because the studies observed
      different disease stages. In five of the seven observational studies, the risk
      ratio ranged from 0.57 (CI = 0.14-2.37) to 1.46 (CI = 0.56-3.79). CONCLUSION: No
      clear evidence for an association between oral contraceptive use during post
      molar follow-up period and the incidence of gestational trophoblastic neoplasia
      was found. Practitioners should no longer avoid their use because of a supposed
      effect which we have shown here to be unsupported by evidence in the literature.

PMID- 16297972
TI  - A case-control study of methylenetetrahydrofolate reductase polymorphisms in
      cervical carcinogenesis.
AB  - OBJECTIVES: Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene
      are thought to be associated with a varying risk of cervical dysplasia. The
      purpose of this trial was to study the role of the two common functional MHTFR
      polymorphisms in a large multiracial population at risk for cervical dysplasia
      and cancer. METHODS: This is a nested case-control study of 376 subjects obtained
      from cohorts enrolled in an ongoing prospective cervical carcinogenesis protocol.
      Cases included invasive cancers (n = 51), and high (n = 50) and low (n = 50)
      grade dysplasia. There were 225 normal controls. Functional MTHFR 677C-->T and
      1298A-->C genotypes were identified. Follow-up cytology data were reviewed for
      the control subjects from the time of study entry until August 2004. RESULTS:
      There is a significant racial difference in allele frequency of the 677C-->T
      polymorphism (P < 0.005). African-American women had an extremely low prevalence
      of the 677T allele (8%). There was no significant difference in the frequency of
      the 677T allele between cases and controls. There is no racial difference in
      allele frequency of the 1298A-->C polymorphism. Also, no significant difference
      was found between cases and controls. Of the 51 cancers, no case was homozygous
      for both aberrant polymorphisms (677T, 1298C), and only 3 cases were heterozygous
      for both. Follow-up data were available for 129 of 225 control subjects (57%).
      Only 15 (12%) have had a subsequent abnormal pap, and there was no association
      with the 677C-->T polymorphism. CONCLUSIONS: We confirm a significant difference
      in the 677T allele frequencies among racial groups. However, there is no
      association of either the 677C-->T or 1298A-->C polymorphisms in cervical
      carcinogenesis. There is no role of the combined polymorphism effect in cervical
      cancer or evidence of prediction for future Pap abnormalities.

PMID- 16297973
TI  - Intra-ventral tegmental area heroin-induced place preferences in rats are
      potentiated by peripherally administered alprazolam.
AB  - The present experiment was designed to replicate and extend previous results of
      an opiate+benzodiazepine interaction in which peripherally administered
      alprazolam was observed to modulate behavior resulting from intravenous
      injections of heroin. As a first step in determining the role of central sites in
      this drug interaction, changes in drug reward (measured by conditioned place
      preference; CPP) were assessed in rats given systemic administration of
      alprazolam coupled with intracranially infused heroin (into the ventral tegmental
      area; VTA). Sprague-Dawley rats were implanted with guide cannula targeting the
      VTA, after which a heroin-induced CPP dose-response curve was determined (2.5-40
      ng administered bilaterally in 0.5 microl/side). In other animals, intra-VTA
      heroin-induced place preferences were challenged with systemically applied
      alprazolam (0.125 mg/kg i.p.). The data confirm that rats dose-dependently
      develop reliable place preferences for a distinct environment paired with
      bilateral VTA-infusions of heroin. Additionally, when a non-rewarding dose of
      alprazolam was combined with a non-rewarding bilateral intra-VTA heroin dose (5
      ng), a significant CPP was produced. These data extend earlier results by
      demonstrating that a systemically applied benzodiazepine can enhance the
      rewarding effects produced by central opiate administration. The results suggest
      that the VTA might be a site where this opiate+benzodiazepine interaction occurs.

PMID- 16297974
TI  - Genetic testing for colon cancer among African-Americans in North Carolina.
AB  - OBJECTIVE: To describe attitudes and correlates of intention to take a genetic
      test for colon cancer in a population-based sample of African-Americans. METHODS:
      African-Americans (n = 658), age 18-70, in North Carolina completed an 11-page
      questionnaire between June-October 2003 that assessed attitudes (familiarity,
      perceived benefits and risks, anxiety, and confidentiality) and intention to take
      a genetic test for colon cancer and various participant characteristics. RESULTS:
      Respondents expressed favorable attitudes and high intention regarding genetic
      testing for colon cancer: 87% would definitely/probably take a genetic test,
      although only 42% had read/heard a lot or some about genetic testing. Most agreed
      that genetic test results should be available to healthcare providers (79%) but
      not to health insurers (62%) or employers (82%). About a third were concerned
      that genetic testing could lead to discrimination. Correlates of intention
      differed by sex. Perceived benefits were significantly positively associated with
      intention among all respondents. However, being married (OR = 2.1, 95% CI: 1.2,
      3.7), doctor as the main source of health information (OR = 2.4, 95% CI: 1.4,
      3.9), and colon cancer family history (OR = 4.3, 95% CI: 1.6, 11.6) were
      significant only for women; some college education (OR = 4.1, 95% CI: 1.7, 9.7),
      importance of sharing test results with relatives (OR = 5.5, 95% CI: 1.6, 18.7),
      and colon cancer screening history (OR = 3.4, 95% CI: 1.6, 7.5) were only
      significant for men. CONCLUSIONS: Respondents expressed high interest in genetic
      testing for colon cancer risk, although confidentiality of test results is a
      concern. Guidelines and policies for genetic testing specific to African
      Americans should be established and future research should examine the prevalence
      of genetic testing.

PMID- 16297975
TI  - Validity of the STRATIFY risk score of falls in nursing homes.
AB  - OBJECTIVE: We investigated the performance of the STRATIFY risk assessment for
      fall risk in nursing home patients. METHODS: This prospective study was conducted
      at the nursing home Antonius Binnenweg in Rotterdam from June 1 to December 31,
      2000. Subjects included newly admitted patients of whom a STRATIFY score was
      obtained. Patients were followed for falls during a person-week observation
      period of 13 weeks. Measurements were age, sex, admission category, STRATIFY
      score, length of stay and number of falls. RESULTS: Of 120 patients (75 women, 45
      men, average age 74.5 years), a STRATIFY score was available. Three months after
      admission 24 of these patients (20%) had died, 56 patients (47%) had been
      discharged and 40 (33%) still resided in the nursing home. Of the 120 patients
      included, 36 patients (30%) had fallen during the observation period. The risk of
      falling in the patient group with a STRATIFY score of 2 or more was 2.35 (95%
      confidence interval: 1.22, 4.52) times that of patients with a lower score. The
      sensitivity of the STRATIFY score was 50% (95% CI: 32, 67), specificity was 76.2%
      (95% CI: 65, 87.5). CONCLUSION: The STRATIFY risk score of falls gave
      disappointing results in our setting.

PMID- 16297976
TI  - Parenting processes and dating violence: the mediating role of self-esteem in low
      and high-SES adolescents.
AB  - The current investigation tested a model in which low self-esteem mediated the
      effects by parenting processes (monitoring, closeness, and support) on measures
      of dating violence (victimization, perpetration, attitudes, and perceptions) in a
      sample of adolescents (n=809; mean age=16.4 years) from both low- and high
      socioeconomic (SES) backgrounds. Hierarchical regression analyses provided
      evidence that low self-esteem partially mediated the link between parenting
      processes and dating violence, with unique differences observed between low- and
      high-SES youth. Specifically, in low-SES youth, low self-esteem mediated the
      relationship between closeness as well as support and dating violence behaviours,
      while in high-SES youth, it only mediated the relationship between maternal
      support and dating violence attitudes.

PMID- 16297977
TI  - Korean patients with chronic lymphocytic leukemia show the similar types of
      chromosomal aberrations as those in Europe and North America.
AB  - Chronic lymphocytic leukemia (CLL) is frequent in the West, but rare in Korea. In
      this study, the frequency of chromosome aberration in Korean CLL patients was
      examined by applying interphase fluorescence in situ hybridization (FISH).
      Conventional cytogenetic test and FISH were performed on bone marrow aspirates
      obtained from 16 CLL patients. By applying DNA probes (Vysis, Downers Grove, IL,
      USA), the deletion in 11q22-23, 13q14, 13q34, and 17p13, and trisomy 12 were
      examined. With FISH, molecular cytogenetic aberration was detected in 10 of 16
      patients [63%, 95% confidence interval (CI) 39-86], whereas with conventional
      cytogenetic test, chromosomal aberration was detected only in 2 out of 13 cases
      (15%, 95% CI 0-35). In total, the cases with one or more chromosomal aberrations
      were 11 out of 16 cases (69%, 95% CI 46-92). The most frequently detected
      aberration was the 13q14 deletion (69%, 95% CI 44-94), followed by trisomy 12
      (19%, 95% CI 0-38) and 11q22 deletion (14%, 95% CI 0-33). No deletion in 17p13
      was observed. In conclusion, CLL in Korean is a heterogeneous genetic disorder,
      showing similar genetic changes in Europe and North America.

PMID- 16297978
TI  - The chemosensitivity to therapy of childhood early B acute lymphoblastic leukemia
      could be determined by the combined expression of CD34, SPI-B and BCR genes.
AB  - We have identified genes differentially expressed in childhood early B acute
      lymphoblastic leukemia at diagnosis, according to chemosensitivity.
      Chemosensitive (M1) and chemoresistant (M3) patients present <5% and >25% of
      residual leukemic blasts at 21 days of treatment, respectively. The expression
      profiles of 4205 genes for 32 patients included in the FRALLE93 protocol have
      been determined using microarray. From differential analysis, CD34, SPI-B and BCR
      distinguished M1 from M3 patients using microarray and RT-PCR data. Linear
      discriminant analysis (LDA) and cross-validation show that the combined
      expression of these three genes classify and predict correctly around 90% and 80%
      of patients, respectively.

PMID- 16297979
TI  - Obesity and asthma.
AB  - Obesity is an important public health problem. An increasing body of data
      supports the hypothesis that obesity is a risk factor for asthma. These data
      include numerous large cross-sectional and prospective studies performed in
      adults, adolescents, and children throughout the world. With few exceptions,
      these studies indicate an increased relative risk of asthma in the obese and
      overweight and demonstrate that obesity antedates asthma. Obesity appears to be a
      particularly important issue for severe asthma. Studies showing improvements in
      asthma in subjects who lose weight, as well as studies showing that obese mice
      have innate airway hyperresponsiveness (AHR) as well as increased responses to
      certain asthma triggers also suggest a causal relationship between obesity and
      asthma. The mechanistic basis for this relationship has not been established. It
      may be that obesity and asthma share some common etiology, such as a common
      genetic predisposition, common effects of in utero conditions, or that obesity
      and asthma are both the result of some other predisposing factor such as physical
      activity or diet. However, there are also plausible biological mechanisms whereby
      obesity could be expected to either cause or worsen asthma. These include co
      morbidities such as gastroesophageal reflux, complications from sleep-disordered
      breathing (SDB), breathing at low lung volume, chronic systemic inflammation, and
      endocrine factors, including adipokines and reproductive hormones. Understanding
      the mechanistic basis for the relationship between obesity and asthma may lead to
      new therapeutic strategies for treatment of this susceptible population.

PMID- 16297980
TI  - Fluorescence probes used for detection of reactive oxygen species.
AB  - Endogenously produced pro-oxidant reactive species are essential to life, being
      involved in several biological functions. However, when overproduced (e.g. due to
      exogenous stimulation), or when the levels of antioxidants become severely
      depleted, these reactive species become highly harmful, causing oxidative stress
      through the oxidation of biomolecules, leading to cellular damage that may become
      irreversible and cause cell death. The scientific research in the field of
      reactive oxygen species (ROS) associated biological functions and/or deleterious
      effects is continuously requiring new sensitive and specific tools in order to
      enable a deeper insight on its action mechanisms. However, reactive species
      present some characteristics that make them difficult to detect, namely their
      very short lifetime and the variety of antioxidants existing in vivo, capable of
      capturing these reactive species. It is, therefore, essential to develop
      methodologies capable of overcoming this type of obstacles. Fluorescent probes
      are excellent sensors of ROS due to their high sensitivity, simplicity in data
      collection, and high spatial resolution in microscopic imaging techniques. Hence,
      the main goal of the present paper is to review the fluorescence methodologies
      that have been used for detecting ROS in biological and non-biological media.

PMID- 16297981
TI  - The Modified Rush Sexual Inventory: preliminary psychometric findings.
AB  - Sexual dysfunction associated with psychiatric disorders and the treatment of
      these disorders can impede a patient's optimal recovery and quality of life.
      Patients are typically reluctant to report their sexual difficulties. Therefore,
      self-report measures that comprehensively and concisely assess sexual
      difficulties are a beneficial contribution to clinical research and practice. The
      Modified Rush Sexual Inventory (MRSI) not only assesses sexual functioning and
      satisfaction using a multiple-choice format, but it also includes an introductory
      section for patients' medical histories and free responses. Though the MRSI has
      been used in clinical trial research, the reliability and validity of the measure
      is unknown. This study presents the initial reliability and validity findings of
      the MRSI.

PMID- 16297982
TI  - Dermatoglyphic anomalies and neurocognitive deficits in sibling pairs discordant
      for schizophrenia spectrum disorders.
AB  - The neurodevelopmental hypothesis of schizophrenia suggests that adverse genetic
      loading in conjunction with environmental factors early in fetal life causes a
      disruption of neural development, decades before the symptomatic manifestation of
      the disease. Neurocognitive deficits have been observed early on the course of
      schizophrenia, and their association with an early developmental brain lesion has
      been postulated. Dermatoglyphics have been analyzed in schizophrenia as markers
      of prenatal brain injury because of their early fetal ontogenesis and
      susceptibility to the same environmental factors that can also affect cerebral
      development. The aim of our study was to conduct a comparative examination of
      neurocognitive functions and dermatoglyphic variables in 89 sibling pairs
      discordant for schizophrenia spectrum disorders. Therefore, we investigated the
      association between these two markers to explore the prenatal origin of cognitive
      deficits in schizophrenia. The affected siblings were significantly impaired on
      all the cognitive variables assessed (Wisconsin Card Sorting Test, Trail Making
      Test and Continuous Performance Test) and had a greater number of dermatoglyphic
      anomalies. These results suggest the influence of intrauterine environmental
      factors in the siblings affected with schizophrenia. However, we did not detect a
      significant association between these two vulnerability markers in the
      schizophrenic patients, suggesting the role of genetic or late environmental
      factors in the origin of the neurocognitive deficits found in these patients.

PMID- 16297983
TI  - Changes in plasma amino acids after electroconvulsive therapy of depressed
      patients.
AB  - There are indications that mood disorders may be related to perturbations in the
      amino acid transmitters. The amino acids may thus be targets of treatment of
      depression. The purpose of this pilot study was to measure the acute effects of a
      single administration of electroconvulsive therapy (ECT) on the plasma levels of
      amino acids in depressed patients. ECT was administered to 10 patients with major
      depressive disorder. Altogether 23 plasma amino acids were analyzed before and at
      2, 6, 24 and 48 h after ECT. The levels of glutamate and aspartate increased at 6
      h after ECT compared with the baseline. Also the levels of total tryptophan
      increased 2-24 h after ECT. There were also elevations in other amino acids at 6
      and 24 h. The levels of gamma-aminobutyric acid (GABA) decreased at 2 h. In this
      study the acute effects of single ECT were associated with changes in the levels
      of glutamate, aspartate, GABA, tryptophan and some other amino acids. The
      preliminary data suggest that the therapeutic effects of ECT in depression may be
      due to mechanisms involving these amino acid transmitters.

PMID- 16297984
TI  - Cross-sex hormone treatment does not change sex-sensitive cognitive performance
      in gender identity disorder patients.
AB  - Cognitive performance in untreated early onset gender identity disorder (GID)
      patients might correspond to their born sex and not to their perceived gender. As
      a current mode of intervention, cross-sex hormone treatment causes considerable
      physical changes in GID patients. We asked, as has been suggested, whether this
      treatment skews cognitive performance towards that of the acquired sex.
      Somatically healthy male and female early onset GID patients were
      neuropsychologically tested before, 3 and 12 months after initiating cross-sex
      hormone treatment, whereas untreated healthy subjects without GID served as
      controls (C). Performance was assessed by testing six cognitive abilities
      (perception, arithmetic, rotation, visualization, logic, and verbalization), and
      controlled for age, education, born sex, endocrine differences and treatment by
      means of repeated measures analysis of variance. GID patients and controls showed
      an identical time-dependent improvement in cognitive performance. The slopes were
      essentially parallel for males and females. There was no significant three-way
      interaction of born sex by group by time for the six investigated cognitive
      abilities. Only education and age significantly influenced this improvement.
      Despite the substantial somatic cross-sex changes in GID patients, no
      differential effect on cognition over time was found between C and GID
      participants. The cognitive performance of cross-sex hormone-treated GID patients
      was virtually identical to that of the control group. The documented test-retest
      effect should be taken into consideration when evaluating treatment effects
      generally in psychiatry.

PMID- 16297985
TI  - The neuropsychology of borderline personality disorder: a meta-analysis and
      review.
AB  - The neuropsychological profile of borderline personality disorder (BPD) is
      unclear. Past investigations have produced seemingly inconsistent results
      concerning precisely what neuropsychological deficits characterize the patient
      with BPD. A meta-analysis of 10 studies was conducted comparing BPD and healthy
      comparison groups on selected neuropsychological measures comprising six domains
      of functioning: attention, cognitive flexibility, learning and memory, planning,
      speeded processing, and visuospatial abilities. BPD participants performed more
      poorly than controls across all neuropsychological domains, with mean effect
      sizes (Cohen's d) ranging from -0.29 for cognitive flexibility to -1.43 for
      planning. The results suggest that persons with BPD perform more poorly than
      healthy comparison groups in multiple neurocognitive domains and that these
      deficits may be more strongly lateralized to the right hemisphere. Although
      neuropsychological testing appears to be sensitive to the neurocognitive deficits
      of BPD, the clinical utility of these results is limited. Implications of these
      findings for future neurocognitive investigations of BPD are discussed.

PMID- 16297986
TI  - Catalytic activity of autoantibodies toward myelin basic protein correlates with
      the scores on the multiple sclerosis expanded disability status scale.
AB  - Autoantibodies toward myelin basic protein (MBP) evidently emerge in sera and
      cerebrospinal fluid of the patients with multiple sclerosis (MS), as well as in a
      MS rodent model, i.e., experimental autoimmune encephalomyelitis (EAE). The
      studies of the last two decades have unveiled somewhat controversial data on the
      diagnostic applicability of anti-MBP autoantibodies as a disease' marker. Here,
      we present the results of new functional analysis of the anti-MBP autoantibodies
      isolated from MS (in patients) and EAE (in mice) sera, based on their proteolytic
      activity against the targeted autoantigen. The activity was shown to be the
      intrinsic property of the IgG molecule. No activity was found in the sera-derived
      antibody fraction of healthy donors and control mice. Sera of 24 patients with
      clinically proven MS at different stages of the disease, and 20 healthy controls
      were screened for the anti-MBP antibody-mediated proteolytic activity. The
      activity correlated with the scores on the MS expanded disability status scale
      (EDSS) (r(2)=0.85, P<0.001). Thus, the anti-MBP autoantibody-mediated proteolysis
      may be regarded as an additional marker of the disease progression.

PMID- 16297987
TI  - Induction of covalent binding antibodies.
AB  - Covalent interactions between antibody combining site residues and substrates
      have been implicated in the catalytic activity of abzymes elicited by design or
      occurring naturally in autoimmune disease. In this study, the potential for
      covalent binding by antibodies (Abs) was investigated by the induction of immune
      responses against molecules presenting chemically reactive haptenic groups.
      Immunogenic conjugates containing a phosphonate diester or a pyruvate carbonyl
      group were used to elicit antibodies that could specifically react with the
      electrophilic moieties. Products formed by covalent binding were detected by a
      western blot technique or by differential ELISA on reduced or unreduced carbonyl
      haptens. Antisera to the diphenylphosphonate contained antibodies with covalent
      reactivity, which increased with immunization. The reactivity was specific to the
      anti-phosphonate response and not to control immune sera induced against the
      unmodified carrier protein. Reactivity was focused on the antibody light (L)
      chain. Antisera to the phenylpyruvate hapten appeared to bind strongly to
      proteins modified by the carbonyl group hapten. However, anti-carrier antisera
      and non-immune sera had similar reactivity, indicating that the pyruvate moiety
      reacts nonspecifically with immunoglobulins. This suggested that affinity
      maturation of antibodies for reversible binding through hemiacetal or Schiff base
      adducts with antigens requires a less reactive carbonyl in the antigen. On the
      other hand, the induction of antibodies with enhanced nucleophilic reactivity
      toward phosphonate esters implies that irreversible binding to the B cell
      receptor can drive clonal expansion and antibody selection. These results support
      a designer strategy for generating nucleophilic abzymes and could also account
      for the occurrence of chemically reactive or catalytic antibodies in natural
      immunity or autoimmunity.

PMID- 16297989
TI  - Increased substance P content in nerve fibers associated with mesenteric veins
      from deoxycorticosterone acetate (DOCA)-salt hypertensive rats.
AB  - This study examined sensory nerves associated with mesenteric arteries and veins
      in sham and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Reactivity
      of arteries and veins to substances released from sensory nerves was also studied
      in vitro using computer-assisted video microscopy. Co-localization of substance P
      (SP) and calcitonin gene-related peptide (CGRP) immunoreactivity (ir) was used to
      evaluate perivascular sensory nerves. Radioimmunoassay was used to quantify SP-
      and CGRP-ir content. Immunohistochemical studies revealed a plexus of SP/CGRP-ir
      nerves associated with arteries and veins. The intensity of SP-ir, but not CGRP
      ir labeling was greater in arteries and veins from DOCA-salt compared to sham
      rats. RIA measurements revealed that the CGRP-ir content of arteries and veins
      was higher than the SP-ir content but there was a significant increase in SP-ir,
      but not CGRP-ir, content in arteries and veins from DOCA-salt rats. SP (0.03-1
      microM) contracted veins and the NK-3 receptor agonist, senktide, mimicked this
      effect. There were no differences in SP or senktide reactivity of veins from sham
      or DOCA-salt rats. SP, but not senktide, relaxed KCl (40 mM) preconstricted
      arteries. CGRP (0.3 microM), acetylcholine (10 microM) and capsaicin (1 microM)
      relaxed KCl-preconstricted arteries and veins. The NK-1 receptor agonist,
      substance P methyl ester relaxed arteries but not veins. These data indicate that
      DOCA-salt hypertension is associated with upregulation of SP content in
      perivascular nerves. NK-3 receptors mediate venoconstriction which is unchanged
      in DOCA-salt hypertension. Increased release of SP from perivenous nerves might
      contribute to the increased venomotor tone in DOCA-salt hypertension.

PMID- 16297988
TI  - Postnatal development of GFAP, connexin43 and connexin30 in cat visual cortex.
AB  - In cat visual cortex, neurons acquire progressively mature functional properties
      during the first postnatal months. The aim of this study was to analyze the
      development of astrocytes during this period. The patterns of expression of the
      glial fibrillary acidic protein (GFAP) as well as of two gap junction proteins
      expressed in astrocytes, connexin43 (Cx43) and connexin30 (Cx30), were
      investigated by immunohistochemistry and optical density measurements, in visual
      cortical areas 17 and 18 at four different ages: 2 weeks (postnatal days 12 to
      15, P12-15), 1 month (P27-31), 2 months (P60-62) and beyond 1 year. Since visual
      experience is a key factor for neural development, the patterns of expression of
      these three proteins were studied both in normally-reared and monocularly
      deprived animals. Interestingly, the distribution of GFAP, Cx43 and Cx30 was
      found to change dramatically but independently of visual experience, during
      postnatal development, even beyond P60. During the first postnatal month, GFAP
      and Cx43 were mainly localized in the white matter underlying the visual cortical
      areas 17 and 18. Then, their distributions evolved similarly with a progressive
      decrease of their density in the white matter associated with an increase in the
      cortex. Connexin30 expression appeared only from the second postnatal month,
      strictly in the cortex and with a laminar distribution which was similar to that
      of Cx43 at the same age. In adults, a specific laminar distribution was observed,
      that was identical for GFAP, Cx43 and Cx30: their density was higher in layers
      II/III and V than in the other cortical layers.

PMID- 16297990
TI  - Adrenomedullin prevents apoptosis in prostate cancer cells.
AB  - The 52-aminoacid peptide adrenomedullin (AM) is expressed in the normal and
      malignant prostate. We have previously shown that prostate cancer cells produce
      and secrete AM, which acts as an autocrine growth inhibitory factor. We have
      evaluated in the present study the role of AM in prostate cancer cell apoptosis,
      induced either by serum deprivation or treatment with the chemotherapeutic agent
      etoposide (which acts as an inhibitor of topoisomerase II). For this purpose we
      over-expressed AM in PC-3, DU 145 and LNCaP cells, which were transfected with an
      expression vector carrying AM. We also treated the parental cell lines with
      synthetic AM in normal culture conditions and in conditions of induced-apoptosis.
      After serum removal, AM prevented apoptosis in DU 145 and PC-3 cells, but not in
      LNCaP cells. When treated with etoposide, AM prevented apoptosis in PC-3 and
      LNCaP cells, but not in DU 145 cells. Cell cycle analysis demonstrated a
      significant decrease in the percentage of AM-overexpressing PC-3 cells in the
      subG0/G1 phase after treatment with etoposide, as compared to the percentage of
      mock-transfected PC-3 treated cells. Western blot showed that protein levels of
      phosphorylated ERK1/2 increased in parental PC-3 cells after treatment with
      etoposide. In PC-3 cells overexpressing AM, phosphorylated ERK1/2 basal levels
      were lower than basal levels of parental PC-3 cells, and treatment with etoposide
      did not result in such an increase. Etoposide produced a significant increase in
      cleaved PARP in parental PC-3 cells. However, PC-3 clones overexpressing AM that
      were treated with etoposide only showed a mild increase in fragmented PARP. The
      ratio Bcl-2/Bax was reduced in parental or mock-transfected PC-3 cells after
      treatment with etoposide. On the contrary, this ratio was not reduced in PC-3
      clones with AM overexpression that were treated with etoposide. All these data
      demonstrate that AM plays a protective role against induced apoptosis in prostate
      cancer cells. These results may have important implications in prostate cancer
      resistance to chemotherapeutic agents.

PMID- 16297991
TI  - Identification of target genes of the transcription factor HNF1beta and HNF1alpha
      in a human embryonic kidney cell line.
AB  - Hepatocyte nuclear factor 1beta (HNF1beta, TCF2) is a tissue-specific
      transcription factor whose mutation in humans leads to renal cysts, genital
      malformations, pancreas atrophy and maturity onset diabetes of the young (MODY5).
      Furthermore, HNF1beta overexpression has been observed in clear cell cancer of
      the ovary. To identify potential HNF1beta target genes whose activity may be
      deregulated in human patients, we established a human embryonic kidney cell line
      (HEK293) expressing HNF1beta conditionally. Using Flp recombinase, we introduced
      wild type or mutated HNF1beta at a defined chromosomal position allowing a most
      reproducible induction of the HNF1beta derivatives upon tetracycline addition. By
      oligonucleotide microarrays we identified 25 HNF1beta-regulated genes. By an
      identical approach, we identified that the related transcription factor HNF1alpha
      (TCF1) affects only nine genes in HEK293 cells and thus is a less efficient
      factor in these kidney cells. The HNF1beta target genes dipeptidyl peptidase 4
      (DPP4), angiotensin converting enzyme 2 (ACE2) and osteopontin (SPP1) are most
      likely direct target genes, as they contain functional HNF1 binding sites in
      their promoter region. Since nine of the potential HNF1beta target genes are
      deregulated in clear cell carcinoma of the ovary, we propose that HNF1beta
      overexpression in the ovarian cancer participates in the altered expression
      pattern.

PMID- 16297992
TI  - Placental cathepsin M is alternatively spliced and exclusively expressed in the
      spongiotrophoblast layer.
AB  - Cathepsin M and cathepsin-3 are cysteine peptidases expressed exclusively in the
      murine placenta. Their expression increases continuously from 11.5 dpc until the
      end of gestation. The cathepsin M gene consists of 8 exons and 7 introns covering
      6 kb of genomic DNA on mouse chromosome 13. Multiple variants of CTSM were
      identified which display alternative splicing of exon 2 or exon 7. Alternative
      splicing of exon 2 does not affect the translated region of CTSM whereas aberrant
      splicing of exon 7 will results in enzymatically inactive versions of CTSM which
      still might retain inhibitory activity towards cysteine peptidases. Besides two
      defined major transcription start sites the putative promoter region comprises of
      a TATA-box and a relatively low (41%) G+C content reflecting its highly specific
      spatial and temporal expression pattern. Similar features are found within the
      promoter region of CTS3 which is highly homologous to CTSM. Both cathepsin M and 
      3 expression are confined to the spongiotrophoblast layer of the mouse placenta
      an expression pattern which is unique among cysteine peptidases located within
      the cluster of cathepsin J-like peptidases on mouse chromosome 13.

PMID- 16297993
TI  - Impact of modeled microgravity on microvascular endothelial cells.
AB  - Microvascular endothelial cells are protagonists in inflammation and
      angiogenesis. They contribute to the integrity of microvasculature by
      synthesizing a large array of cytokines, growth factors and mediators active on
      the endothelium itself, on smooth muscle cells and circulating leukocytes.
      Because space flight (i) associates with vascular impairment and (ii) modulates
      the cytokine network, we evaluated the effect of modeled microgravity on
      microvascular 1G11 cells. We found that modeled microgravity reversibly inhibits
      endothelial growth and this correlates with an upregulation of p21, a cyclin
      dependent kinases inhibitor. By protein array, we found that microgravity
      inhibits the synthesis of interleukin 6, an event that may contribute to growth
      retardation. We also detected increased amounts of nitric oxide, a mediator of
      inflammatory responses, a potent vasodilator and a player in angiogenesis. The
      increased synthesis of nitric oxide is due, at least in part, to an upregulation
      of endothelial nitric oxide synthase. Because low levels of IL-6 might contribute
      to endothelial growth retardation as well as to the enhancement of nitric oxide
      synthesis, we hypothesize a central role of IL-6 in modulating microvascular
      endothelial cell behaviour in modeled microgravity.

PMID- 16297994
TI  - Fission yeast homologue of Tip41-like proteins regulates type 2A phosphatases and
      responses to nitrogen sources.
AB  - A fission yeast (Schizosaccharomyces pombe) gene encoding a member of the TIP41
      like protein family was identified and characterized. Deletion of the fission
      yeast tip41 gene leads to slower growth when ammonium chloride is the nitrogen
      source, but the growth rate is not affected when adenine is the nitrogen source.
      The tip41 mutant cells also enter the G1 phase of the cell cycle earlier than
      wild-type cells in response to nitrogen starvation. Overexpression of tip41(+)
      causes cell death, spherical cell morphology and blocks the shift to G1 phase
      upon nitrogen starvation. Overexpression of tip41(+) increases the activity of
      type 2A phosphatase. In a ppa2 deletion strain with reduced PP2A activity,
      overexpression of tip41(+) no longer blocks the shift to G1 upon nitrogen
      starvation. These results suggest that fission yeast Tip41 plays a role in
      cellular responses to nitrogen nutrient conditions at least partly through
      regulation of type 2A phosphatase activity.

PMID- 16297995
TI  - Influence of heart rate on the detectability and reproducibility of multislice
      computed tomography for measuring coronary calcium score using a pulsating
      calcified mock-vessel in comparison with electron beam tomography.
AB  - BACKGROUND: The influence of heart rate on detectability and reproducibility of
      multislice computed tomography (MSCT) for measuring coronary calcium score was
      evaluated using pulsating calcified mock-vessels and compared with electron beam
      tomography (EBT). MATERIALS AND METHODS: Four calcified mock-vessels with 200-350
      HU were made to pulsate at a rate of 40-80 beat/min. Retrospective ECG-gating
      MSCT (Light Speed Ultra 16) scanning with 0.625 mm slice-thickness was performed
      twice at each pulsation rate. For comparison, EBT (Imatron C150 XP) was performed
      with 3 and 1.5 mm beam collimation with prospective ECG-gating and calcium scores
      were measured. RESULTS: The comparison revealed that MSCT did not have better
      reproducibility than EBT, but the calcium scores with MSCT were less influenced
      by pulsation rates than those with EBT. Especially in mild calcification, the
      calcium scores decreased with EBT with 3 mm beam collimation with increasing
      pulsation rate, but the scores were stable in any rate with MSCT. CONCLUSION:
      MSCT effectively detects coronary calcification, especially mild calcification,
      without being influenced by heart rate. This is accomplished by reducing the
      partial volume effect in the through plane using sub millimeter slice thickness,
      and using appropriate reconstruction methods, which improve temporal resolution.

PMID- 16297997
TI  - Relationship between insulin resistance and left ventricular diastolic
      dysfunction in patients with impaired glucose tolerance and type 2 diabetes.
AB  - AIM: The aim of this study was to explore the relationship between insulin
      resistance (IR) and the left ventricular diastolic function in patients with type
      2 diabetes and subjects with impaired glucose tolerance (IGT). METHODS: The study
      included 119 subjects who underwent oral glucose tolerance test (OGTT). IR was
      assessed using Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and
      Quantitative Insulin Sensitivity Check Index (QUICKI). Left ventricular diastolic
      function was assessed using trans-thoracic Doppler echocardiography. RESULTS:
      Based on the OGTT results, 29 subjects had normal glucose tolerance (NGT), 20
      subjects had impaired glucose tolerance (IGT), and 70 patients had type 2
      diabetes. There were significant differences among the patients in groups with
      NGT, IGT and diabetes regarding HOMA-IR (4.20 +/- 1.20 vs. 6.45 +/- 3.83 vs. 8.70
      +/- 6.26; P < 0.001) and QUICKI (0.54 +/- 0.11 vs. 0.49 +/- 0.08 vs. 0.47 +/-
      0.08; P < 0.001). In subjects with NGT, IGT and patients with diabetes, the
      pulsed Doppler transmitral variables were: E-wave (0.72 +/- 0.16 cm/s vs. 0.62 +/
      0.13 cm/s vs. 0.58 +/- 0.17 cm/s; P < 0.001), A-wave (0.61 +/- 0.13 cm/s vs.
      0.62 +/- 0.11 cm/s vs. 0.71+/- 0.14 cm/s; P = 0.006) and E/A ratio (1.22 +/- 0.33
      vs. 1.02 +/- 0.24 vs. 0.85 +/- 0.26; p < 0.001). The proportion of subjects with
      an E/A ratio <1 was 27.6% in the group with NGT, 55% in the group with IGT and
      75.7% in the group with diabetes (P < 0.001). The E/A ratio correlated with HOMA
      IR (r = -0.30, p = 0.001) and QUICKI (r = 0.37, p < 0.0001). Multiple linear
      regression model showed that IR (assessed by QUICKI) was an independent correlate
      of diastolic dysfunction (P = 0.034). CONCLUSIONS: In subjects with impaired
      glucose tolerance and patients with type 2 diabetes, insulin resistance is
      associated with impaired diastolic function of the left ventricle.

PMID- 16297996
TI  - The relationship between inflammation and arterial stiffness in patients with
      essential hypertension.
AB  - BACKGROUND: Data about the correlation between augmentation index (AIx), timing
      of the reflected waveform (T(r)) and inflammatory markers in patients with
      essential hypertension are not yet well established. The aim of this study was to
      compare plasma high-sensitivity C-reactive protein (hsCRP), white blood cell
      count and fibrinogen in hypertensive patients and in normotensive controls and to
      assess the relationship between inflammatory markers and arterial stiffness.
      METHODS: Forty-two healthy middle-aged patients with untreated stage I-II
      essential hypertension and 42 sex- and age-matched controls were recruited in the
      study. Pulse wave analysis was used to assess AIx and T(r). RESULTS: Plasma
      hsCRP, white blood cell count, AIx and T(r) were significantly higher in the
      patients with essential hypertension. In multiple regression analysis, AIx
      correlated positively with age, female gender, mean arterial pressure and
      log(hsCRP), and negatively with heart rate and height (R(2)=0.75, p<0.001). T(r)
      correlated negatively with log(hsCRP) (r=-0.34, p=0.002) for the whole study
      group. However, after adjusting for mean arterial pressure, age, height, heart
      rate and sex to the regression model, no correlation was revealed between
      log(hsCRP) and T(r) (p=0.35) as the dependent variable (R(2)=0.48, p<0.001).
      CONCLUSIONS: Untreated hypertensive patients with low or moderate total
      cardiovascular risk had significantly increased blood hsCRP and white blood cell
      count and arterial stiffness, expressed as AIx and T(r). AIx correlated
      independently with hsCRP in multiple regression analysis. Measurement of arterial
      stiffness and inflammation can be suggested as an additional tool to assess
      cardiovascular risk in hypertensive patients with low or moderate total
      cardiovascular risk as estimated by traditional risk factors.

PMID- 16297998
TI  - Overview of issues pertaining to the manufacture, distribution, and use of
      antimicrobials in animals and other information relevant to animal antimicrobial
      use data collection in the United States.
AB  - This paper provides condensed literature review and contextual information
      concerning antimicrobial use in animals and antimicrobial use data collection
      techniques. Information is summarized into the following topics: (I)
      antimicrobial use for animal growth promotion; (II) regulatory framework for
      approval of veterinary antimicrobials and feed additives in the United States;
      (III) animal health product manufacturing and distribution networks; (IV)
      existing estimates of animal antimicrobial use in the United States; (V)
      additional sources for animal use data in the United States; (VI) recommendations
      from international expert groups; (VII) animal antimicrobial use surveillance
      systems in other nations and (VIII) human use data collection systems in the
      United States.

PMID- 16297999
TI  - Microarray analysis of the transcriptional response to single or multiple doses
      of ionizing radiation in human subcutaneous fibroblasts.
AB  - BACKGROUND AND PURPOSE: Transcriptional profiling of fibroblasts derived from
      breast cancer patients might improve our understanding of subcutaneous radiation
      induced fibrosis. The aim of this study was to get a comprehensive overview of
      the changes in gene expression in subcutaneous fibroblast cell lines after
      various ionizing radiation (IR) schemes in order to provide information on
      potential targets for prevention and to suggest candidate genes for SNP
      association studies aimed at predicting individual risk of radiation-induced
      morbidity. PATIENTS AND METHODS: Thirty different human fibroblast cell lines
      were included in the study, and two different radiation schemes; single dose
      experiments with 3.5 Gy or fractionated with 3 x 3.5 Gy. Expression analyses were
      performed on unexposed and exposed cells after different time points. The IR
      response was analyzed using the statistical method Significance Analysis of
      Microarrays (SAM). RESULTS: While many of the identified genes were involved in
      known IR response pathways like cell cycle arrest, proliferation and
      detoxification, a substantial fraction of the genes were involved in processes
      not previously associated with IR response. Of particular interest is genes
      involved in ECM remodelling, Wnt signalling and IGF signalling. Many of the genes
      were identified after a single dose, but transcriptional changes in genes related
      to ROS scavenging and ECM remodelling were most profound after a fractionated
      scheme. CONCLUSIONS: We have identified a number of IR response pathways in
      fibroblasts derived from breast cancer patients. Besides previously identified
      pathways, we have identified new pathways and genes that could be relevant for
      prevention and intervention studies of subcutaneous radiation-induced fibrosis as
      well as being candidates for SNP association studies.

PMID- 16298000
TI  - The effects of tangential radiotherapy on lung clearance in breast cancer
      patients.
AB  - PURPOSE: The aim of this study was to investigate the effects of tangential
      radiotherapy (RT) on lung clearance in the patients with breast cancer by using
      (99m)Tc-DTPA aerosol scintigraphy. MATERIAL AND METHODS: Thirty-three female
      patients [non-smoker: 20, ex-smoker: 13] performed surgery and systemic
      chemotherapy for breast carcinoma [47+/-13 years] were included in the study. All
      patients underwent (99m)Tc-DTPA aerosol scintigraphy prior to RT (pre RT), midway
      through RT (mid RT) and after RT (post RT). Total dose was 50 Gy in modified
      radical mastectomy and 60 Gy in lumpectomy (2 Gy/fraction). Posterior dynamic
      images of lungs were obtained immediately after the inhalation of (99m)Tc-DTPA
      aerosol. RESULTS: Pulmonary function tests were normal in three measurements for
      all cases. In the ex-smokers, there was no significant difference among pre RT,
      mid RT and post RT clearance values in both lungs. Pre RT lung clearance in non
      smoker group did not differ from that in ex-smokers. However, the lung clearance
      for non-smoker group showed significantly increase following RT. CONCLUSION: In
      this study, we observed that tangential radiotherapy caused an increase in the
      lung clearance in the cases of non-smokers even in non-irradiated lung, and that
      the effect of RT on lung clearance was closely depended on smoking habit before
      RT.

PMID- 16298003
TI  - Synchronized brain activity during rehearsal and short-term memory disruption by
      irrelevant speech is affected by recall mode.
AB  - EEG coherence as a measure of synchronization of brain activity was used to
      investigate effects of irrelevant speech. In a delayed serial recall paradigm 21
      healthy participants retained verbal items over a 10-s delay with and without
      interfering irrelevant speech. Recall after the delay was varied in two modes
      (spoken vs. written). Behavioral data showed the classic irrelevant speech effect
      and a superiority of written over spoken recall mode. Coherence, however, was
      more sensitive to processing characteristics and showed interactions between the
      irrelevant speech effect and recall mode during the rehearsal delay in theta (4
      7.5 Hz), alpha (8-12 Hz), beta (13-20 Hz), and gamma (35-47 Hz) frequency bands.
      For gamma, a rehearsal-related decrease of the duration of high coherence due to
      presentation of irrelevant speech was found in a left-lateralized fronto-central
      and centro-temporal network only in spoken but not in written recall. In theta,
      coherence at predominantly fronto-parietal electrode combinations was indicative
      for memory demands and varied with individual working memory capacity assessed by
      digit span. Alpha coherence revealed similar results and patterns as theta
      coherence. In beta, a left-hemispheric network showed longer high
      synchronizations due to irrelevant speech only in written recall mode. EEG
      results suggest that mode of recall is critical for processing already during the
      retention period of a delayed serial recall task. Moreover, the finding that
      different networks are engaged with different recall modes shows that the
      disrupting effect of irrelevant speech is not a unitary mechanism.

PMID- 16298001
TI  - Feasibility of using intensity-modulated radiotherapy to improve lung sparing in
      treatment planning for distal esophageal cancer.
AB  - BACKGROUND AND PURPOSE: To evaluate the feasibility whether intensity-modulated
      radiotherapy (IMRT) can be used to reduce doses to normal lung than three
      dimensional conformal radiotherapy (3 DCRT) in treating distal esophageal
      malignancies. PATIENTS AND METHODS: Ten patient cases with cancer of the distal
      esophagus were selected for a retrospective treatment-planning study. IMRT plans
      using four, seven, and nine beams (4B, 7B, and 9B) were developed for each
      patient and compared with the 3 DCRT plan used clinically. IMRT and 3 DCRT plans
      were evaluated with respect to PTV coverage and dose-volumes to irradiated normal
      structures, with statistical comparison made between the two types of plans using
      the Wilcoxon matched-pair signed-rank test. RESULTS: IMRT plans (4B, 7B, 9B)
      reduced total lung volume treated above 10 Gy (V(10)), 20 Gy (V(20)), mean lung
      dose (MLD), biological effective volume (V(eff)), and lung integral dose
      (P<0.05). The median absolute improvement with IMRT over 3DCRT was approximately
      10% for V(10), 5% for V(20), and 2.5 Gy for MLD. IMRT improved the PTV
      heterogeneity (P<0.05), yet conformity was better with 7B-9B IMRT plans. No
      clinically meaningful differences were observed with respect to the irradiated
      volumes of spinal cord, heart, liver, or total body integral doses. CONCLUSIONS:
      Dose-volume of exposed normal lung can be reduced with IMRT, though clinical
      investigations are warranted to assess IMRT treatment outcome of esophagus
      cancers.

PMID- 16298002
TI  - The impact of introducing intensity modulated radiotherapy into routine clinical
      practice.
AB  - BACKGROUND AND PURPOSE: Intensity modulated radiotherapy (IMRT) at the Royal
      Marsden Hospital London was introduced in July 2001. Treatment delivery was
      dynamic using a single-phase technique. Concerns were raised regarding increased
      clinical workload due to introduction of new technology. The potential increased
      use of resources was assessed. PATIENTS AND METHODS: IMRT patient selection was
      within guidelines of clinical trials and included patients undergoing prostate
      plus pelvic lymph node (PPN) irradiation and head and neck cancer (HNC)
      treatment. Patient planning, quality assurance and treatment times were collected
      for an initial IMRT patient group. A comparative group of patients with advanced
      HNC undergoing two- or three-phase conventional radiotherapy, requiring matched
      photon and electron fields, were also timed. RESULTS: The median overall total
      planning time for IMRT was greater for HNC patients compared to the PPN cohort.
      For HNC the overall IMRT planning time was significantly longer than for
      conventional. The median treatment time for conventional two- or three-phase HNC
      treatments, encompassing similar volumes to those treated with IMRT, was greater
      than that for the IMRT HNC patient cohort. A reduction in radiographer man hours
      per patient of 4.8h was recorded whereas physics time was increased by 4.9h per
      patient. CONCLUSIONS: IMRT currently increases overall planning time. Additional
      clinician input is required for target volume localisation. Physics time is
      increased, a significant component of this being patient specific QA.
      Radiographer time is decreased. For HNC a single phase IMRT treatment has proven
      to be more efficient than a multiple phase conventional treatment. IMRT has been
      integrated smoothly and efficiently into the existing treatment working day. This
      preliminary study suggests that IMRT could be a routine treatment with efficient
      use of current radiotherapy resources.

PMID- 16298004
TI  - N2 event-related potential correlates of response inhibition in an auditory
      Go/Nogo task.
AB  - The aim of this study was to investigate the event-related potential correlates
      of response inhibition in the N2 time window, specifically in the auditory
      modality. A paired tone Go/Nogo paradigm elicited an enhanced fronto-central
      negativity in the Nogo condition, which was accompanied by a concurring inferior
      fronto-temporal positivity. In contrast to most previous studies our data provide
      evidence for a fronto-central Nogo-N2 component in the auditory modality.

PMID- 16298005
TI  - Kinetic evaluation of photosensitivity in genetically engineered neurons
      expressing green algae light-gated channels.
AB  - Neurons become photosensitive by genetically introducing one of green algae
      derived protein, channelrhodopsin-2 (ChR2). Here, we quantitatively investigated
      the rapidness of the light-gated current of ChR2 expressed in PC12 cells using
      blue light-emitting diode (LED) light. The light-gated current consists of two
      components, inactivating and non-inactivating. The magnitude of inactivating
      component was almost linearly related to the light intensity. The non
      inactivating component showed a tendency to saturate at high illumination. Both
      the activation and inactivation rates of the light-gated current were linearly
      dependent on the light intensity. However, the activation rate (turning-on rate)
      is about 10-fold faster than the inactivation rate. Although the turning-off time
      constant was little dependent on the light intensity, that at the end of 1s light
      pulse was about two-fold larger than that at 20 ms. Neurons are also made
      photosensitive by the expression of ChR2 in the living animal. Since both the
      turning-on and turning-off time constants of light-gated current was smaller than
      the membrane time constant of neurons, the LED light illumination of the
      photosensitive neurons was enough to evoke action potentials in a pulse-to-pulse
      manner in an acute slice of hippocampus.

PMID- 16298007
TI  - P1- and VPg-transgenic plants show similar resistance to Potato virus A and may
      compromise long distance movement of the virus in plant sections expressing RNA
      silencing-based resistance.
AB  - Nicotiana benthamiana was transformed with P1 or VPg cistron of Potato virus A
      (PVA, genus Potyvirus). For both transgenes, T1 progeny displayed (i) resistance
      to PVA infection, (ii) susceptibility, or (iii) systemic infection followed by
      recovery of new leaves from PVA infection (RC), regardless of the transgene. In
      RC plants, fully recovered leaves contained no detectable PVA RNA, were highly
      resistant to challenge inoculation with PVA, and had barely detectable steady
      state levels of transgene mRNA; transgene-homologous siRNA was not detected, in
      contrast to leaves undergoing recovery. Tops in RC plants and PVA-susceptible
      transgenic plants were replaced with scions from wild-type plants; only scions on
      the latter became PVA-infected. These findings suggest that vascular movement of
      PVA from lower, infected parts of RC plants was compromised in the recovered
      section expressing RNA silencing-based resistance, which adds a novel dimension
      to the current models for potyvirus movement.

PMID- 16298006
TI  - Experimental and modelling study of different process modes for retroviral
      production in a fixed bed reactor.
AB  - Pseudotype vectors are promising for gene transfer in many gene therapy
      approaches, however, low-vector concentration in batch cultures and high
      temperature-dependent decay do limit sufficiently large-scale production. To
      overcome these obstacles, the kinetic relations of cell growth and vector
      formation in different culture modes need to be understood. Effective
      optimisation of process modes is needed to achieve sufficient yields.
      Experimental and modelling studies were carried out in order to analyse the
      impact of different process modes such as perfusion, perfused fed-batch or
      repeated-batch on vector titer and productivity. Retroviral pseudotype vector,
      derived from the murine leukaemia virus carrying the HIV-1 envelop protein MLV
      (HIV-1) were produced using a 200 ml fixed bed reactor for high cell density
      cultivation on macroporous carriers. After starting the cultivation in batch
      mode, the reactor was either run in perfusion, perfused fed-batch or repeated
      batch. A mathematical model of the bioreaction was developed on the basis of
      experimental data measured in culture dishes. The ability of the model to
      describe all different process modes of fixed-bed cultivation without additional
      fitting of the parameters was proven by three long-term cultivations for more
      than 400 h. The results of optimisation with the aid of the model, leads to the
      conclusion that perfusion with optimised harvest cycles and fed flows, result in
      a higher yield in comparison to batch or fed batch culture.

PMID- 16298008
TI  - Protection of oligonucleotides against nucleases by pegylated and non-pegylated
      liposomes as studied by fluorescence correlation spectroscopy.
AB  - Antisense phosphodiester oligonucleotides (ONs), complexed to carriers such as
      cationic liposomes, inhibit the production of proteins. The biochemical and
      biophysical phenomena that govern the extent of this inhibition are still not
      fully understood. Major biological barriers limiting a pronounced antisense
      effect are the cellular entry and endosomal escape of the ONs containing
      liposomes, the release of the ONs from the liposomes and the extra- and
      intracellular degradation of the ONs. In this paper we focus on the latter
      barrier and evaluate, by fluorescence correlation spectroscopy (FCS), to what
      extent phosphodiester ONs complexed to DOTAP/DOPE liposomes, are protected
      against degradation by nucleases. Liposomes studied were either with or without a
      polyethyleneglycol (PEG) moiety at the surface. Using non-pegylated liposomes the
      phosphodiester ONs were initially adequately protected when exposed to DNase I.
      Indeed, in the mechanism for lipoplex formation as suggested by others, the ONs
      become trapped between lipid bilayers and are therefore shielded from the
      environment. However, after a few hours the phosphodiester ONs no longer stayed
      intact. This was explained by a gradual fusion of the lipoplexes in time thereby
      spontaneously releasing phosphodiester ONs. Using pegylated liposomes, a
      substantial fraction of the phosphodiester ONs degraded immediately after
      exposing the complexes to DNase I. Based on experimental evidence we suggest that
      the presence of the PEG-chains influences lipoplex formation so that the ONs are
      not trapped between lipid bilayers and therefore remain accessible by the DNase I
      enzyme.

PMID- 16298009
TI  - Nano-carriers for DNA delivery to the lung based upon a TAT-derived peptide
      covalently coupled to PEG-PEI.
AB  - Gene therapy aimed at the respiratory epithelium holds therapeutic potential for
      diseases such as cystic fibrosis and lung cancer. Polyethylenimine (PEI) has been
      utilized for gene delivery to the airways. In this study, we describe a new
      modification of PEI, in which an oligopeptide related to the protein transduction
      domain of HIV-1 TAT was covalently coupled to 25 kDa PEI (PEI) through a
      heterobifunctional polyethylenglycol (PEG) spacer resulting in a TAT-PEG-PEI
      conjugate. Improved DNA reporter gene complexation and protection was observed
      for small (approximately 90 nm) polyplexes as well as significantly improved
      stability against polyanions, Alveofact, bronchial alveolar lining fluid and
      DNase. To determine polyplex toxicity in vitro, MTT assays were performed and,
      for in vivo testing, the mice bronchial alveolar lavage was investigated for
      total cell counts, quantity of neutrophils, total protein and TNF-alpha
      concentration. All parameters suggest significantly lower toxicity for TAT-PEG
      PEI. Transfection efficiencies of both PEI and TAT-PEG-PEI polyplexes with DNA
      were studied under in vitro conditions (A549) and in mice after intratracheal
      instillation. While luciferase expression in A549 cells was much lower for TAT
      PEG-PEI (0.2 ng/mg protein) than for PEI (2 ng/mg), significantly higher
      transfection efficiencies for TAT-PEG-PEI were detected in mice. Reporter gene
      expression was distributed through bronchial and alveolar tissue. Thus, TAT-PEG
      PEI represents a new approach to non-viral gene carriers for lung therapy,
      comprising protection for plasmid DNA, low toxicity and significantly enhanced
      transfection efficiency under in vivo conditions.

PMID- 16298010
TI  - Site specific gene delivery in the cardiovascular system.
AB  - Gene therapy holds great promise for treating both genetic and acquired
      disorders. However, progress toward effective human gene therapy has been
      thwarted by a number of problems including vector toxicity, poor targeting of
      diseased tissues, and host immune and inflammatory activity to name but a few of
      the challenges. Gene therapy for cardiovascular disease has been the subject of
      many fewer clinical trials than other disorders such as cancer or cystic
      fibrosis. Nevertheless, the challenges are comparable. The present paper reports
      a review of investigations related to our hypothesis that site specific
      cardiovascular gene therapy represents an approach that can lead to both
      optimizing efficacy and reducing the impact of gene vector-related systemic
      adverse effects. We report experimental studies demonstrating proof of principle
      in three areas: gene therapy for heart valve disease, gene delivery stents, and
      gene therapy to treat cardiac arrhythmias. Heart valve disease is the second most
      common indication for open heart surgery and is now only treatable by surgical
      removal or repair of the diseased heart valve. Our investigations demonstrate
      that gene vectors can be immobilized on the surface of prosthetic heart valve
      leaflets thereby enabling a therapeutic genetic modification of host cells around
      the valve annulus and on the leaflet. Other animal studies have shown that
      vascular stents used to relieve arterial obstruction can also be used as gene
      delivery systems to provide therapeutic vector constructs that can both locally
      prevent post stenting reobstruction, known as in-stent restenosis, and treat the
      underlying vascular disease. Cardiac arrhythmias are the cause of sudden death
      due to heart disease and affect millions of others on a chronic basis. Our group
      has successfully investigated in animal studies localized gene therapy using an
      ion channel mutation to treat atrial arrhythmias.

PMID- 16298011
TI  - Freeze-dried formulations for in vivo gene delivery of PEGylated polyplex
      micelles with disulfide crosslinked cores to the liver.
AB  - A stable, freeze-dried formulation consisting of a core-shell-type polyplex with
      a poly(ethylene glycol) (PEG) shell (polyplex micelles) was prepared from a
      polyion complex of plasmid DNA (pDNA) and thiolated PEG-poly(L-lysine) block
      copolymers. The use of lyoprotectants was avoided by crosslinking the core with
      disulfide bonds. The crosslinked polyplex micelles (CPMs) showed excellent
      stability during freeze-drying and reconstitution processes, which is in sharp
      contrast with the formation of visible agglomerates from the non-crosslinked
      polyplex micelles (NCPMs) after a similar process. A thiolation degree higher
      than 13% of the lysine residues was required to achieve sufficient tolerability
      of the CPMs during the freeze-drying/reconstitution cycle. Dynamic light
      scattering measurements and atomic force microscopy observations demonstrated
      that the original size and shape of the CPMs with a thiolation degree of higher
      than 13% were maintained even after the freeze-drying. Furthermore, the CPMs
      reconstituted from the freeze-dried state achieved a transfection efficiency as
      high as that of the original samples. The intravenous injection of the CPM with a
      thiolation degree of 37% into mice via the orbital vein led to an appreciably
      uniform gene expression of a yellow fluorescence protein variant (Venus) in the
      liver, while no gene expression was observed in the case of the free pDNA
      injection. The procedure of disulfide crosslinking of the polyplex micell core
      allows the preparation of non-viral gene vectors as a powder formulation without
      the use of any lyoprotectants. This achievement is certainly useful for
      pharmaceutical applications and exhibits many advantages, including easy
      concentration adjustments of dosing samples, long-term storage stability, and
      large-scale production reproducibility.

PMID- 16298012
TI  - Comparison of the obesity risk and related factors in employed and unemployed
      (housewife) premenopausal urban women.
AB  - The aim of the study was to assess the interaction between occupational and
      leisure time physical activities (LTPA) as well as socioeconomical status (SES),
      lifestyles and dietary habits on the prevalences of overweight and obesity in
      employed and unemployed (housewife) urban premenopausal Turkish women. Among 1209
      women surveyed 508 premenopausal ones between 20 and 45 years of age were
      included in the study. Overweight prevalence in the employed (47.3% versus 36.2%)
      and obesity prevalence in the unemployed women (housewives) were higher (42.2%
      versus 11.6%). The ratio of family history for obesity, co-morbid diseases, habit
      of <30 min of walking/day, consuming meals twice/day, preference of vegetables
      were higher in the housewives. Employed women had a higher SES scoring, education
      level, percentage of no habit of walking, consuming meals thrice per day,
      preference for protein, smoking and alcohol consumption. Housewife group had a
      higher glucose level measured while employed group higher total cholesterol. Age,
      waist circumference (WaC), having one or two meals/day versus three or four
      meals/day, having lunch at home versus outdoor lunch, having one parity versus
      none were the main predictors of obesity. Our results indicated that lifestyle
      interventions should be afforded for increasing LTPA for both employed and
      unemployed women since overweight and obesity prevalences are high in both.

PMID- 16298014
TI  - Natural history and prognostic indicators of survival in cirrhosis: a systematic
      review of 118 studies.

PMID- 16298013
TI  - Comparison of sequence changes of precore and core promoter regions in HBeAg
      positive chronic hepatitis B patients with and without HBeAg clearance in
      lamivudine therapy.
AB  - BACKGROUND/AIMS: The aim of this study was to compare the serial sequence changes
      of precore and core promoter regions in hepatitis B e antigen (HBeAg)-positive
      chronic hepatitis B (CHB) patients with and without HBeAg clearance in lamivudine
      treatment. METHODS: Precore and core promoter genes of the hepatitis B virus
      (HBV) were sequenced from five serial serum samples of 74 HBeAg-positive CHB
      patients received lamivudine for 9-12 months (34 complete responders and 40 non
      responders). RESULTS: Before lamivudine therapy, stepwise logistic regression
      analysis disclosed that ALT level > or =300 U/L, A1896 mutant, and log HBV DNA
      levels were the major determinants for complete response. In addition, Cox
      regression showed that age < 35 years and G1752 mutant were independent factors
      for sustained response. Compared with complete responders, a higher frequency of
      mutation in nucleotides 1773, 1802, 1803, 1845, 1850, and 1858 was found in the
      non-responders during therapy. Lamivudine therapy resulted in a further increase
      in T1762/1764 mutants and a further decrease in A1896 mutant during treatment and
      after HBeAg clearance in complete responders. CONCLUSIONS: T1762/A1764 mutation
      (not A1896) played an important role in lamivudine-induced HBeAg clearance.
      Moreover, T1773, C1802, G1803, T1846, A1850, and C1858 mutations might have
      significant correlation with HBeAg nonseroconversion.

PMID- 16298015
TI  - Push-pull tests evaluating in situ aerobic cometabolism of ethylene, propylene,
      and cis-1,2-dichloroethylene.
AB  - In situ aerobic cometabolic transformations of ethylene, propylene, and cis-1,2
      dichloroethylene (c-DCE), by microorganisms stimulated on propane, were examined
      in groundwater contaminated with c-DCE and trichloroethylene (TCE). In situ
      measurements were performed by conducting field push-pull tests, which consisted
      of injecting site groundwater amended with a bromide tracer and combinations of
      propane, dissolved oxygen (DO), nitrate, ethylene, propylene, c-DCE, and TCE into
      existing monitoring wells and sampling the same wells over time. Mass balance and
      transformation rate calculations were performed after adjusting for dilution
      losses using measured tracer concentrations. Initial rates of propane utilization
      were very low; rates increased substantially following sequential additions of
      propane and DO. Evidence that propane and DO additions had stimulated organisms
      expressing a propane monoxygenase enzyme system and that had the capability to
      transform chlorinated aliphatic hydrocarbons (CAHs) included: (1) the
      transformation of injected ethylene and propylene to the cometabolic byproducts
      ethylene oxide and propylene oxide, (2) the transformation of c-DCE, and (3) the
      inhibition of these transformations in the presence of coinjected acetylene, a
      known monoxygenase mechanism-based inactivator. These results suggest that a
      series of push-pull tests performed with nontoxic chemical probes can be useful
      for detecting and monitoring in situ aerobic cometabolism of CAHs.

PMID- 16298017
TI  - Relationship between taste thresholds and hunger under debate.
AB  - We determined taste recognition thresholds for six compounds (sucrose, fructose,
      sodium chloride, quinine sulphate, PROP and liquorice) in fasting students and,
      in the same subjects, after a meal. The testing procedure was the staircase
      method in blind conditions. Although taste sensitivity may vary with hormonal
      status, our results did not show any significant difference in taste recognition
      thresholds between hunger and satiety. Our Bayesian analysis did not corroborate
      the hypothesis of increased sensitivity to nutrition-related tastants in the
      fasting state that was recently supported by data obtained with the two
      alternative forced-choice method.

PMID- 16298016
TI  - Superposition of borehole-to-surface voltage residuals for Vadose Zone plume
      delineation.
AB  - An injected tracer field experiment was conducted at the University of Idaho
      Ground Water Field Laboratory to evaluate the application of borehole-to-surface
      voltage measurements for delineation of the tracer distribution in partially
      saturated, fractured basalt. A tap water tracer was injected into a fracture
      dominated, salt-water plume formed during a previous salt-water injection
      experiment. The tap water tracer was injected into a central injection well under
      constant hydraulic head for 34 days. The injection well was surrounded by seven
      test boreholes. Each borehole contained several copper wire electrodes for
      borehole-to-surface potential measurements between a surface grid of 224 copper
      sulfate, porous pot electrodes. Eight pole-pole, borehole-to-surface voltage data
      sets were acquired during each measurement period by energization of a selected
      electrode in each of the eight boreholes. Predicted voltages for a uniform earth
      (homogeneous and isotropic) potential model (finite difference) were subtracted
      from each data set (for its respective current source location), and the voltage
      residuals superposed to create new data sets with greater measurement sensitivity
      and coverage, to aid in interpretation. These data sets were collected over four
      measurement periods during tap water injection and four measurement periods
      during the subsequent 64-day drainage phase. The data were interpreted with the
      use of three-dimensional models and by comparisons with other electrical and
      hydrological observations. Results indicate that superposition of multiple data
      sets of voltage residuals significantly improved the lateral resolution of
      subsurface bulk resistivity changes that occurred over time.

PMID- 16298018
TI  - Implicit attitudes towards genetically modified (GM) foods: a comparison of
      context-free and context-dependent evaluations.
AB  - Past research on attitudes towards GM food has focused on measuring explicit
      attitudes. Here we compared implicit attitudes towards GM foods with explicit
      attitudes towards GM foods. We used the Go No-Go task to investigate context-free
      implicit evaluations of GM foods and compared these with evaluations made in the
      context of ordinary and organic foods. Semantic differential scales were used to
      evaluate explicit attitudes towards GM foods. As expected, explicit attitudes
      towards GM foods were found to be neutral. However, contrary to our hypotheses,
      participants were found to hold positive, rather than neutral, implicit attitudes
      towards GM foods when these were assessed in a context free manner. In addition,
      neutral implicit attitudes were found when attitudes were assessed in the context
      of ordinary or organic foods, again contrasting with our hypotheses. These
      results imply that implicit attitudes towards GM food are more positive than
      anticipated and may lead to approach behaviour towards such products. Thus, given
      the choice, consumers are likely to accept GM food although other incentives may
      be needed if alternative foods are available.

PMID- 16298019
TI  - Correlates of daily caffeine consumption.
AB  - A study of 376 young British adults showed that estimated daily caffeine
      consumption increased with age, and was associated with smoking and greater
      alcohol consumption. Non-consumers of caffeine avoided tea and coffee (even the
      de-caffeinated form). Level of caffeine consumption was not associated with
      impulsivity, sociability, extraversion or trait anxiety.

PMID- 16298020
TI  - 15,16-dihydrotanshinone I suppresses the activation of BV-2 cell, a murine
      microglia cell line, by lipopolysaccharide.
AB  - Microglial activation has been implicated in neurodegenerative diseases.
      Therefore, inhibition of inflammation mediated by microglia is a strategy in
      neurodegenerative disease therapy. In this study, we isolated cryptotanshinone
      and 15,16-dihydrotanshinone I from Salvia miltiorrhiza, a traditional Korean herb
      medicine, by bioactivity-guided fractionation based on inhibitory effect on
      nitric oxide in a lipopolysaccharide-stimulated BV-2 cells, a murine microglial
      cell line. 15,16-Dihydotanshinoe I suppressed the expression of not only
      inducible nitric oxide synthase but also of interleukin-1beta, tumor necrosis
      factor-alpha, and of TNF-alpha converting enzyme.

PMID- 16298021
TI  - [Use of low molecular weight heparin for medical prophylaxis by European
      geriatricians].
AB  - PURPOSE: Many hospitalised elderly patients are at increased risk of venous
      thromboembolism (VTE). The aim of this study was to assess the rate and duration
      of medical utilization of low molecular weight heparin (LMWH) for VTE prevention
      by European geriatricians. METHOD: A questionnaire was sent to 94 geriatricians
      of the European Academy for Medicine of Ageing (EAMA), to be filled out for each
      patient older than 65 years of their institutions who received LMWH during 1 day
      of December 2000. RESULTS: In the 37 centers that participated (representing 11
      different European countries) 2912 patients were present on the day of the study:
      857 patients in acute care, 367 in rehabilitation care, 1568 in long-term care
      and 141 in day hospital. Prophylaxis by LMWH was given to 284 medical patients
      (9.75%, mean age 82.2 years). Use of LMWH was more frequent in acute and
      rehabilitation care (22.4% and 9.8%) than in long-term care (3.1%). The main risk
      factors in patients with LMWH prophylaxis were: bedridden (53%), infectious
      disease (18%), heart failure (17.6%), venous insufficiency (17.6%), paralysis of
      lower limbs (16.6%), recent stroke (15%) and malignancy (10%). The duration of
      the treatment for VTE prophylaxis exceeded 30 days in 51 patients (12%) and one
      year in 15 patients (3.3%). CONCLUSION: In Europe, VTE prophylaxis by LMWH is
      widely used in elderly medical patients without specific guidelines in this
      population. Further studies are necessary to evaluate the appropriate duration of
      prophylaxis in very prolonged immobilization.

PMID- 16298022
TI  - [Severe hyperhomocysteinemia revealing homocystinuria in two young adults with
      mild phenotype].
AB  - INTRODUCTION: To the request of total plasma homocysteine determination in the
      investigation of vascular disease, diagnosis of homocystinuria in young adult
      patients with mild phenotype is not so rare. EXEGESIS: A 26-year-old man
      developed embolic cerebral infarction and a 22-year-old woman presented a right
      renal venous thrombosis one week after delivery. In each case, high concentration
      of total plasma homocysteine was first found and plasma and urinary amino acids
      analysis later on directed the diagnosis towards homocystinuria. Finally, reduced
      skin fibroblast cystathionine beta-synthase activity confirmed the diagnosis of
      homocystinuria. CONCLUSION: Total plasma homocysteine determination must be
      determined for screening for hyperhomocysteinemia in young adults with venous
      thromboembolism without characteristic phenotypic features of homocystinuria.

PMID- 16298023
TI  - Small bowel bacterial overgrowth may not affect bone mineral density in older
      people.
AB  - BACKGROUND & AIMS: Small bowel bacterial overgrowth (SBBO) may be associated with
      malnutrition, diarrhea, and weight loss. Recently, bone mineral density (BMD) in
      patients with SBBO was reported to be lower, and SBBO may be an important factor
      in the development of metabolic bone disease. However, the subjects in these
      studies were relatively young patients with intestinal diseases. There is no
      information on the effect of SBBO on BMD in older people. METHOD: Seventeen
      relatively active and 33 disabled older people participated in this study. SBBO
      was determined by a breath hydrogen (H2) test after ingestion of a glucose
      solution. BMD of the lumbar spine and femur were measured using a dual energy X
      ray absorptiometry scan (DEXA). RESULTS: One healthy control and 11 disabled
      subjects were SBBO-positive. The Z-scores of the lumbar spine were not
      statistically different between groups, and a high incidence of disorders, >70%,
      was seen in all groups. On the other hand, there were significant differences in
      the femoral BMD between the healthy controls and the SBBO-negative (P<0.001) and
      SBBO-positive (P<0.05) groups. No significant difference was seen in femoral BMD
      between SBBO-positive and SBBO-negative institutionalized people. CONCLUSION:
      SBBO seems to have little effect on BMD in people approximately 80 years old.

PMID- 16298024
TI  - Vaxfectin enhances immunogenicity and protective efficacy of P. yoelii
      circumsporozoite DNA vaccines.
AB  - We evaluated the capacity of the cationic lipid based formulation, Vaxfectin, to
      enhance the immunogenicity and protective efficacy of DNA-based vaccine regimens
      in the Plasmodium yoelii murine malaria model. We immunized Balb/c mice with
      varying doses (0.4-50 microg) of plasmid DNA (pDNA) encoding the P. yoelii
      circumsporozoite protein (PyCSP), either in a homologous DNA/DNA regimen (D-D) or
      a heterologous prime-boost DNA-poxvirus regimen (D-V). At the lowest pDNA doses,
      Vaxfectin substantially enhanced IFA titers, ELISPOT frequencies, and protective
      efficacy. Clinical trials of pDNA vaccines have often used low pDNA doses based
      on a per kilogram weight basis. Formulation of pDNA vaccines in Vaxfectin may
      improve their potency in human clinical trials.

PMID- 16298025
TI  - Feasibility of a mass vaccination campaign using a two-dose oral cholera vaccine
      in an urban cholera-endemic setting in Mozambique.
AB  - We conducted a study to assess the feasibility and the potential vaccine coverage
      of a mass vaccination campaign using a two-dose oral cholera vaccine in an urban
      endemic neighbourhood of Beira, Mozambique. The campaign was conducted from
      December 2003 to January 2004. Overall 98,152 doses were administered, and
      vaccine coverage of the target population was 58.6% and 53.6% for the first and
      second rounds, respectively. The direct cost of the campaign, which excludes the
      price of the vaccine, amounted to slightly over 90,000 dollars, resulting in the
      cost per fully vaccinated person of 2.09 dollars, which is relatively high.
      However, in endemic settings where outbreaks are likely to occur, integrating
      cholera vaccination into the routine activities of the public health system could
      reduce such costs.

PMID- 16298026
TI  - Universal vaccination of children against influenza: are there indirect benefits
      to the community? A systematic review of the evidence.
AB  - We present a systematic review of the effectiveness of vaccinating healthy
      children to protect others. Primary studies were identified by searching standard
      electronic databases, internet sites, trials registers and citation lists to
      January 2004 and subjected to critical appraisal. Eight randomised controlled
      trials, three community studies and three economic evaluations met the inclusion
      criteria. The evidence suggests that vaccinating healthy children against
      influenza has the potential for reducing the impact of influenza epidemics.
      However, further evidence is needed as limitations of study design or execution
      mean that the community benefits are difficult to quantify.

PMID- 16298027
TI  - Strategies for mapping neutralizing epitopes: one way and two sides.

PMID- 16298029
TI  - Heterologous prime-boost strategy to overcome weak immunogenicity of two
      serosubtypes in hexavalent Neisseria meningitidis outer membrane vesicle vaccine.
AB  - In the hexavalent meningococcal B OMV vaccine (HexaMen), two of the six Porin A
      proteins present are weakly immunogenic in mice and humans. We investigated the
      possibility that the lower immunogenicity of these serosubtypes (P1.7-2,4 and
      P1.19,15-1) could be overcome by using HexaMen and monovalent OMVs in
      heterologous immunisation protocols. Whereas HexaMen priming on day 0 followed by
      a monovalent P1.7-2,4 OMV boosting on day 28 (specific boost) did not result in
      higher titres against P1.7-2,4 (on day 42), the reverse order of immunisations
      (specific priming) resulted in significantly higher ELISA and SBA titres, but
      with lower avidity. For the strongly immunogenic PorA P1.5-1,2-2, all strategies
      gave high antibody responses, while avidity was highest after two monovalent P1.5
      1,2-2 OMV immunisations. Based on the improved antibody titres obtained by
      specific priming with the weakly immunogenic PorA, we extended our study with
      combined P1.7-2,4 and P1.19,15-1 priming followed by two HexaMen booster
      immunisations. This resulted in higher ELISA and SBA titres against these weakly
      immunogenic PorAs, while the response against the other four PorAs was
      unaffected. Also, we observed an increase in antibody avidity using this
      schedule, indicating that affinity maturation has occurred. In conclusion, we
      found that specific priming, rather than specific boosting with monovalent OMVs,
      gave a significant rise in the serosubtype-specific immune response against a
      weakly immunogenic PorA, with high avidity antibodies in an extended immunisation
      schedule.

PMID- 16298028
TI  - Highly pathogenic avian influenza (H7N7): vaccination of zoo birds and
      transmission to non-poultry species.
AB  - In 2003 an outbreak of highly pathogenic avian influenza virus (H7N7) struck
      poultry in The Netherlands. A European Commission directive made vaccination of
      valuable species in zoo collections possible under strict conditions. We
      determined pre- and post-vaccination antibody titres in 211 birds by
      haemagglutination inhibition test as a measure of vaccine efficacy. After booster
      vaccination, 81.5% of vaccinated birds developed a titre of > or =40, while
      overall geometric mean titre (GMT) was 190 (95% CI: 144-251). Birds of the orders
      Anseriformes, Galliformes and Phoenicopteriformes showed higher GMT, and larger
      percentages developed titres > or =40 than those of the other orders. Antibody
      response decreased with increasing mean body weight in birds > or =1.5 kg body
      weight. In the vicinity of the outbreak, H7N7 was detected by RT-PCR in wild
      species (mallards and mute swans) kept in captivity together with infected
      poultry, illustrating the potential threat of transmission from poultry into
      other avian species, and the importance of protecting valuable avian species by
      means of vaccination.

PMID- 16298030
TI  - Toe-to-hand transfers: more than 20 years follow-up of five post-traumatic cases.
AB  - In post-traumatic losses of the thumb and fingers, reconstruction can be
      performed with success using various combinations of toe transfers. In this
      study, we have presented second toe and combined toe transfers which have been
      followed up for more than 20 years. Second toe transfer was used in four patients
      for reconstruction of the thumb. Combined second and third toe transfer was
      performed in two patients with a metacarpal hand for finger reconstruction. Long
      term follow-up results show that patients with toe-to-hand transfers have
      acceptable adaptation to the reconstructed hand and good hand function. Toe
      transfer should be individually planned and carefully executed to obtain optimal
      results and minimal disability in the donor foot.

PMID- 16298031
TI  - Assessment of heavy metal bioavailability in contaminated sediments and soils
      using green fluorescent protein-based bacterial biosensors.
AB  - A green fluorescent protein (GFP)-based bacterial biosensor Escherichia coli
      DH5alpha (pVLCD1) was developed based on the expression of gfp under the control
      of the cad promoter and the cadC gene of Staphylococcus aureus plasmid pI258.
      DH5alpha (pVLCD1) mainly responded to Cd(II), Pb(II), and Sb(III), the lowest
      detectable concentrations being 0.1 nmol L(-1), 10 nmol L(-1), and 0.1 nmol L(
      1), respectively, with 2h exposure. The biosensor was field-tested to measure the
      relative bioavailability of the heavy metals in contaminated sediments and soil
      samples. The results showed that the majority of heavy metals remained adsorbed
      to soil particles: Cd(II)/Pb(II) was only partially available to the biosensor in
      soil-water extracts. Our results demonstrate that the GFP-based bacterial
      biosensor is useful and applicable in determining the bioavailability of heavy
      metals with high sensitivity in contaminated sediment and soil samples and
      suggests a potential for its inexpensive application in environmentally relevant
      sample tests.

PMID- 16298032
TI  - Life-course influences on mortality at older ages: evidence from the Oslo
      Mortality Study.
AB  - Several studies have investigated the cumulative influence of disadvantage acting
      from early to adult life. And they suggest that risk of death increases in a
      cumulative fashion. Few studies have investigated the life-course influences on
      social inequality in mortality in early old age. In this study we wanted to
      follow a cohort through their adult working age into retirement and investigate
      pathways that may give increased risk of mortality. A cohort of all inhabitants
      in the age range 68-72 who lived in the municipality of Oslo on 1st January 1990
      was selected. Data were obtained by linking censuses from 1960, 1970 and 1980
      with tax registry in 1990 and death registry 1990-1998. Independent variables
      were occupational class in 1960, 1970 and 1980 and household income in 1990.
      Occupational class was coded as manual and non-manual and household income as
      above or below median household income. A cumulative model was developed by
      adding times of disadvantage. Then a pathway model was developed which
      investigated the specific trajectories individuals followed. Most of the
      increased risk of death was explained by individuals' social conditions in 1990.
      In the cumulative model, there was no clear gradient in the groups between the
      bottom and top categories. This suggests that the cumulative model is not
      important in the high mortality age and that the relative importance of a
      cumulative effect varies by stages of the life course.

PMID- 16298033
TI  - Skin tumorigenic potential of aflatoxin B1 in mice.
AB  - Aflatoxin B1 (AFB1) has been classified as a category I human carcinogen, which
      is responsible for a high incidence of hepatocellular carcinoma. Since exposure
      to AFB1 can occur through skin contact in addition to ingestion and inhalation,
      the carcinogenic potential of topically applied AFB1 on mouse skin was
      investigated. Our results show that single topical application of AFB1 (80 nmol)
      as a tumor initiator, followed by twice weekly application of 12-tetradecanoyl
      phorbol myristate acetate (TPA, 4 nmol), resulted in tumor formation after 13
      weeks. However, no tumorigenic potential was observed when AFB1 (16 nmol) was
      used either as a complete carcinogen or as a tumor promoter (4 nmol).
      Histological analysis of skin showed squamous cell carcinoma in the AFB1/TPA
      treated group. The application of AFB1 as a complete carcinogen, an initiator or
      a promoter after 24 weeks demonstrated widespread degenerative and necrotic
      changes in hepatic tissue as well, suggesting liver to be the target organ
      following percutaneous absorption. Additionally, twice weekly topical application
      of AFB1 caused significant induction of cutaneous CYP IA monoxygenases without
      any effect on hepatic levels while glutathione-S-transferase activity was induced
      more in the liver than skin. The topical application of AFB1 also resulted in
      increased hepatic and cutaneous lipid peroxidation with concomitant depletion of
      glutathione content. It is likely that due to higher induction of hepatic GST
      activity, products of lipid peroxidation may be detoxified and therefore unable
      to cause DNA damage making mice resistant to hepatic tumor formation. The overall
      results indicate a tumor initiating potential of AFB1 in mice and suggest that
      continued dermal exposure of AFB1, even at low doses, might lead to degenerative
      changes in hepatocytes.

PMID- 16298034
TI  - Research strategy for developing key information on bromate's mode of action.
AB  - Bromate is produced when ozone is used to treat waters that contain trace amounts
      of bromide ion. It is also a contaminant of hypochlorite solutions produced by
      electrolysis of salt that contains bromide. Both ozone and hypochlorite are
      extensively used to disinfect drinking water, a process that is credited with
      reducing the incidence of waterborne infections diseases around the world. In
      studies on experimental animals, bromate has been consistently demonstrated to
      induce cancer, although there is evidence of substantial species differences in
      sensitivity (rat>mouse>hamster). There are no data to indicate bromate is
      carcinogenic in humans. An issue that is critical to the continued use of ozone
      as a disinfectant for drinking water in bromide-containing waters depends heavily
      on whether current predictions of carcinogenic risk based on carcinogenic
      responses in male rats treated with bromate are accurate at the much lower
      exposure levels of humans. Thiol-dependent oxidative damage to guanine in DNA is
      a plausible mode of action for bromate-induced cancer. However, other mechanisms
      may contribute to the response, including the accumulation of alpha2u-globulin in
      the kidney of the male rat. To provide direction to institutions that have an
      interest in clarifying the toxicological risks that bromate in drinking water
      might pose, a workshop funded by the Awwa Research Foundation was convened to lay
      out a research strategy that, if implemented, could clarify this important public
      health issue. The technical issues that underlie the deliberations of the
      workshop are provided in a series of technical papers. The present manuscript
      summarizes the conclusions of the workgroup with respect to the type and timing
      of research that should be conducted. The research approach is outlined in four
      distinct phases that lay out alternative directions as the research plan is
      implemented. Phase I is designed to quantify pre-systemic degradation,
      absorption, distribution, and metabolism of bromate and to associate these with
      key events for the induction of cancer and develop an initial pharmacokinetic
      (PK) model based on preliminary studies. Phase II will be implemented if it
      appears that there is a linear relationship between external dose and key event
      responses and is designed to gather carcinogenesis data in female rats in the
      absence of alpha2u-globulin-induced nephropathy which the workgroup concluded was
      a probable contributor to the responses observed in the male rats for which
      detailed dose-response data were collected. If the key events and external
      dosimetry are found not to be linear in Phase I, Phase III is initiated with a
      screening study of the auditory toxicity of bromate to determine if it is likely
      to be exacerbated by chronic exposure. If this occurs, auditory toxicity will be
      further evaluated in Phase IV. If auditory toxicity is determined unlikely to
      occur, an alternative chronic study in female rats to the one identified in Phase
      II will be implemented to include exposure in utero. This was recommended to
      address the possibility that the fetus may be more susceptible. One of the three
      options are to be implemented in Phase IV depending upon whether preliminary data
      indicated that chronic auditory toxicity, reproductive and/or developmental
      toxicities, or a combination of these outcomes is necessary to characterize the
      toxicology of low dose exposures to bromate. Each phase of the research will be
      accompanied by further development of pharmacokinetic models to guide collection
      of appropriate data to meet the needs of the more sophisticated studies. It is
      suggested that a Bayesian approach be utilized to develop a final risk model
      based upon measurement of prior observations from the Phase I studies and the set
      of posterior observations that would be obtained from whichever chronic study is
      conducted.

PMID- 16298035
TI  - MRI morphology of the levator ani muscle, endopelvic fascia, and urethra in women
      with stress urinary incontinence.
AB  - OBJECTIVE: To evaluate pathomorphologic changes of the levator ani muscle,
      endopelvic fascia, and urethra in women with stress urinary incontinence (SUI) by
      MRI. STUDY DESIGN: Fifty-four women with SUI were examined by MRI (1.5T): body
      phased-array coil, axial and coronal proton-density-weighted sequences. RESULTS:
      The urethral sphincter muscle showed a reduced thickness of its posterior portion
      (37%), an omega shape (13%) or higher signal intensity (50%); its abnormal
      configuration was associated with an increased signal intensity in 70% (p=0.001).
      The levator ani muscle comprised an unilateral loss of substance in 30%, a higher
      signal intensity in 28%, and altered origin in 19%. Central defects of the
      endopelvic fascia were present in 39% (n=21), lateral defects in 46%. There was a
      significant association between loss of the symphyseal concavity of the anterior
      vaginal wall and lateral fascial defects (p=0.001) and levator ani changes
      (p=0.016). CONCLUSION: MRI yields findings supporting current theories on the
      pathogenesis of SUI.

PMID- 16298036
TI  - A statistical approach for analyzing structural and regulative information in
      prokaryotic genomes.
AB  - Although DNA is iconized as a straight double helix, it does not exist in this
      canonical form in biological systems. Instead, it is characterized by sequence
      dependent structural and dynamic deviations from the monotonous regularity of the
      canonical B-DNA. Despite the complexity of the system, we showed that DNA
      structural and dynamics large-scale properties can be predicted starting from the
      simple knowledge of nucleotide sequence by adopting a statistical approach. The
      paper reports the statistical analysis of large pools of different prokaryotic
      genes in terms of the sequence-dependent curvature and flexibility. Conserved
      features characterize the regions close to the Start Translation Site, which are
      related to their function in the regulation system. In addition, regular patterns
      with three-fold periodicity were found in the coding regions. They were
      reproduced in terms of the nucleotide frequency expected on the basis of the
      genetic code and the pertinent occurrence of the aminoacid residues.

PMID- 16298038
TI  - Subcellular localization of beta-catenin and APC proteins in colorectal
      preneoplastic and neoplastic lesions.
AB  - Adenomatous polyposis coli (APC) is a tumor suppressor gene whose main function
      is the destabilization of beta-catenin, a key effector of the Wnt signaling
      pathway. This gene is defective in familial adenomatous polyposis (FAP), a
      dominantly inherited disease, but inactivation of APC has been reported also in
      most sporadic colorectal tumors and it is considered an early event in colorectal
      tumorigenesis. The aim of the present study was to evaluate the intracellular
      ultrastructural distribution of beta-catenin and APC proteins in epithelial cells
      of normal colorectal mucosa, aberrant crypt foci (ACF, an early premalignant
      lesion) and cancer. We used the immunogold electron microscopic method to
      identify both proteins. Normal colonic epithelial cells showed a strong
      membranous expression of beta-catenin and lacked cytoplasmic and nuclear
      expression. Normal cells showed APC localization pattern characterized by diffuse
      nuclear expression and along the plasma membrane. In ACF and in carcinoma an
      absent or reduced membranous expression of beta-catenin was associated with an
      increased nuclear and cytoplasmatic expression. In aberrant crypt foci and
      carcinoma, APC was evident inside the nucleus and at the level of cell-cell
      junctions, but it was decreased in the cytoplasm. This method allowed the
      accurate localization of proteins of the Wnt signaling pathway in the early steps
      of colorectal carcinogenesis. The similar pattern of subcellular distribution of
      APC and beta-catenin in dysplastic ACF and colorectal cancer suggests that ACF
      are precursor lesions of sporadic and FAP-associated colorectal carcinoma.

PMID- 16298037
TI  - ERE-independent ERalpha target genes differentially expressed in human breast
      tumors.
AB  - The classical pathway for estrogen receptor (ER) signaling is mediated by ER
      binding to an estrogen response element (ERE) in DNA. ERalpha can also act via a
      nonclassical pathway by altering the activities of other transcription factors
      (e.g., Sp1, AP-1, or NF-kappaB) at their cognate sites on DNA. We previously
      generated a mutant form of ERalpha (E207A/G208A) that does not bind to EREs, and
      therefore lacks signaling via the classical pathway but retains signaling via the
      nonclassical pathway. In the current study, we introduce this mutant ERalpha into
      MDA-MB231 ERalpha-negative breast carcinoma cells to identify nonclassical
      pathway genes that respond to 17beta-estradiol (E2), selective estrogen receptor
      modulators (SERMs) tamoxifen (TAM) or raloxifene (RAL), or the estrogen
      antagonist ICI 182,780 (ICI). Consistent with a role for nonclassical signaling
      in SERM action, microarray analyses identify 268 responsive nonclassical ERalpha
      pathway target genes. ICI elicits the largest number of nonclassical genes,
      followed by RAL, TAM, and E2. Custom microarrays containing identified
      nonclassical ERalpha responsive genes are used to compare gene expression in
      human breast tumor (n = 34) and normal mammary epithelial cell (n = 9) samples. A
      subset of nonclassical genes (n = 32) are differentially expressed in breast
      tumors. In summary, we show that nonclassical ERalpha pathway target genes
      exhibit a range of transcriptional responses to SERMs and identify targets of
      this pathway as potentially relevant to breast cancer. The identification of
      nonclassical ERalpha target genes offers new insight into estrogen receptor
      signaling and cross talk with pathways that mediate breast tumor response to SERM
      therapy.

PMID- 16298039
TI  - Secretome analysis of microarray data reveals extracellular events associated
      with proliferative potential in a cell line model of breast disease.
AB  - It is widely believed that breast cancer develops in a multistep process with
      premalignant lesions preceding invasive carcinoma. The characterization of
      molecular events associated with premalignant progression would improve our
      understanding of carcinogenesis and greatly benefit the development of early
      detection methods and chemoprevention strategies. However, the molecular biology
      of precancerous breast disease is poorly understood. To better characterize
      extracellular events associated with disease progression, such as cell-cell and
      cell-extracellular matrix (ECM) signaling, we analyzed gene expression profiles
      for the set of genes coding for secreted proteins (the secretome) in a cell line
      model of human proliferative breast disease (PBD). PBD describes a series of
      preneoplastic changes in the inner lining of milk glands associated with a
      dramatic increase in the risk of breast cancer. We used a series of cell lines
      with increasing proliferative propensity, and cell cultures were grown on
      matrigel to emulate in vivo growth and ECM interactions. Microarray analysis
      identified two clusters of secretome genes with expression profiles correlating
      to PBD progression. Some of the identified genes have previously been associated
      with breast malignancies, and our results suggest that changes in expression for
      these genes begin in the premalignant stage, offering potential use for early
      detection and as chemotherapeutic targets. RT-PCR validation demonstrates the
      reliability of the microarray results.

PMID- 16298040
TI  - Endocrine disrupting compounds and prostate cancer.
AB  - Prostate cancer is a major health concern and is treated based on its hormone
      dependence. Agents that alter hormone action can have substantial biological
      effects on prostate cancer development and progression. As such, there is
      significant interest in uncovering the potential effects of endocrine disrupting
      compound (EDC) exposure on prostate cancer. The present review is focused on
      agents that alter hormone action in the prostate and how they may impact cancer
      growth or treatment.

PMID- 16298041
TI  - Low-frequency common fragile sites: link to neuropsychiatric disorders?
AB  - Common fragile sites are unstable chromosomal regions that predispose chromosomes
      to breakage and rearrangements. Recombinogenic DNA sequences encompassing these
      sites may contribute to both germinal and somatic genomic mutations, and the
      genomic instability at these regions might cause severe inherited disorders or
      predispose to cancer. In this review, we discuss the characterization of common
      fragile site FRA13A within the neurobeachin gene, which is involved in
      development and function of the central nervous system. We raise the possibility
      of an implication of common fragile sites in neuropsychiatric disorders and
      overview previous and recent reports concerning individual variability of
      expression of common fragile sites in human populations.

PMID- 16298042
TI  - Degradation of dyehouse effluent containing C.I. Direct Blue 199 by processes of
      ozonation, UV/H2O2 and in sequence of ozonation with UV/H2O2.
AB  - The decolorization and mineralization of cotton dyeing effluent containing C.I.
      Direct Blue 199 (DB 199) by advanced oxidation processes (AOPs) such as
      ozonation, UV/H(2)O(2), and in sequence of ozonation with UV/H(2)O(2) processes
      were evaluated in this study. By ozonation alone, the color removal was almost
      100% for DB 199 and greater than 80% for dye bath effluent rapidly within 5 and
      15 min, respectively. Meanwhile, the reduction of total organic carbon (TOC) was
      about 60% for DB 199 and almost no change for dye bath effluent, respectively due
      to incomplete mineralization. On the other hand, by UV/H(2)O(2) alone, the color
      removing not only took longer time but obtained lower removal efficiencies for DB
      199 and dye bath effluent about 80% and 95% in 30 and 120 min, respectively.
      Nevertheless, it was more effective than ozonation for TOC removal while about
      75% and 80% in 30 and 120 min, respectively. As a result, this study conducted
      the combination with the above two processes in order to shorten time demand as
      well as the higher removal efficiencies of both color and TOC simultaneously.
      Thus, the sequence process was designed to begin with ozonation to rapidly remove
      color proficiently, following by UV/H(2)O(2) in order to promptly remove
      remaining TOC efficiently. The successful process design by sequence of ozonation
      with UV/H(2)O(2) has proved the significant improvement for the removal of both
      color and TOC in dye bath effluent shortly. Besides, the lab prepared dye
      solution was substantially much easier to be decolorized than field dye bath
      effluent so that the lab results were utilized to design the further applications
      of pilot or full scale.

PMID- 16298044
TI  - Effects of gap size and UV dosage on decolorization of C.I. Acid Orange 7 by
      UV/H2O2 process.
AB  - Wastewater from textile processing plants can be highly colored and difficult to
      decolorize. During the past few years attention has been drawn to chemical
      techniques that could be used to textile wastewater decolorization. A crucial
      feature in designing such systems is the optimization of operating conditions. In
      the present study, advanced oxidation treatment, the UV/H(2)O(2) process has been
      applied to decolorization of the azo dye C.I. Acid Orange 7 (AO7) in aqueous
      solution in a batch photo reactor. The effects of the reactor gap size and UV
      dosage on decolorization of dye have been investigated. The method of study
      involved monitoring the rate of dye solution decolorization during irradiation by
      a low-pressure mercury lamp and varying gap size and volume of the reactor. The
      rate of color removal was studied by measuring of the absorbance at
      characteristic wavelength. The gap size of the reactor was adjusted by different
      depths of the reactor. The results of this study showed that the removal
      efficiency of AO7 is optimal with 0.3 cm gap size and 83.33 Wl(-1) of UV dosage.

PMID- 16298043
TI  - Sand sorption process for the removal of sodium dodecyl sulfate (anionic
      surfactant) from water.
AB  - Granite sand was used to adsorb anionic surfactant, sodium dodecyl sulfate (SDS)
      from water at natural pH 6.25. The effect of adsorbent size, pH, temperature and
      amount of adsorbent has been examined. The results indicate that the Langmuir
      model provides the best correlation of experimental data. Thermodynamic
      parameters like entropy, enthalpy and free energy of adsorption were evaluated.
      Decreasing the temperature accelerates the adsorption of SDS onto sand surface.
      The kinetic data were analyzed by using pseudo-first order Lagergren equation.
      Adsorption of SDS was exothermic and dominated by physisorption with activation
      energy (Ea) 33.65 kJ mol(-1). In addition, regeneration of granite sand by
      washing with Fenton likes reagent was examined. The results suggested that
      granite sand is suitable as a sorbent material for recovery and adsorption of SDS
      from aqueous solutions in view of its effectiveness and cheaper cost.

PMID- 16298045
TI  - A survey of accidents occurring during the transport of hazardous substances by
      road and rail.
AB  - A study of 1932 accidents that occurred during the transport of hazardous
      substances by road and rail from the beginning of the 20th century to July 2004
      was carried out. The results obtained show an increase in the frequency of
      accidents over time. More than half of the accidents happened on roads (63%). The
      most frequent accidents were releases (78%), followed by fires (28%), explosions
      (14%) and gas clouds (6%). The various causes of the accidents, the type of
      substance involved and the consequences for the population (number of people
      killed, injured or evacuated) were also analysed. Among the diverse measures
      taken to improve this situation, the training of professional people involved in
      transportation seems to be of major importance.

PMID- 16298046
TI  - Determination of lead in human saliva by combined cloud point extraction
      capillary zone electrophoresis with indirect UV detection.
AB  - A micelle-mediated phase separation without added chelating agents to
      preconcentrate trace levels of lead in human saliva as a prior step to its
      determination by capillary electrophoresis has been developed. The enrichment
      step is based on the cloud point extraction of lead with the non-ionic surfactant
      PONPE 7.5 in the absence of chelating agent. The surfactant-rich phase was
      diluted with acetonitrile and the resultant solution was injected directly into
      the CE instrument. Factors affecting the combined methodology such as surfactant
      rich phase diluting agent, buffer pH and concentration, applied voltage, sample
      preparation and presence of additives were studied in detail. A BGE of 20 mM
      imidazole containing 30% acetonitrile, pH 6.20 was found to be optimal for the
      separation of lead from other saliva constituents. Indirect detection was
      performed at 205 nm. The detection limit value of lead for the preconcentration
      of 8 ml of saliva was 11.4 microg l(-1). The calibration graph using the
      preconcentration system was linear with a correlation coefficient of 0.997 at
      levels near the detection limits up to at least 400 microg l(-1). The
      reproducibility (R.S.D.) on the basis of migration time and peak area were better
      than 0.68 and 3.6%, respectively. The method was successfully applied to the
      determination of lead in human saliva.

PMID- 16298047
TI  - Photocatalytic degradation of triazinic ring-containing azo dye (Reactive Red
      198) by using immobilized TiO2 photoreactor: bench scale study.
AB  - The decolorization and degradation of triazinic ring-containing azo dye by using
      TiO(2)-immobilized photoreactor is reported. A simple and easy method was used
      for the immobilization of photocatalyst. Reactive Red 198 (RR 198) was used as
      model compound. Photocatalytic degradation processes were performed using a 5 L
      (bench scale) solution containing dye. Batch mode immersion type method was used
      for the treatment of dye solution. UV-vis, ion chromatography (IC) and chemical
      oxygen demand (COD) analyses were employed to evaluate the results of the
      photocatalytic degradation of RR 198. Dye solution was completely decolorized in
      relatively short time (35 min) after UV irradiation in combination with hydrogen
      peroxide. The results verified that all of the dye molecules were destructed.
      Kinetics analysis indicates that the dye photocatalytic decolorization rates
      followed first order model (R(2) = 0.99). Ion chromatography analysis was used to
      investigate the formation and destruction of aliphatic carboxylic acids and
      formation of inorganic anions during the process. Formate and oxalate anions were
      detected as main aliphatic carboxylic intermediates, which were further oxidized
      slowly to CO(2). UV/TiO(2)/H(2)O(2) process proved to be capable of successful
      decolorization and degradation of the RR 198.

PMID- 16298048
TI  - Potential use of advanced process control for safety purposes during attack of a
      process plant.
AB  - Many refineries and commodity chemical plants employ advanced process control
      (APC) systems to improve throughputs and yields. These APC systems utilize
      empirical process models for control purposes and enable operation closer to
      constraints than can be achieved with traditional PID regulatory feedback
      control. Substantial economic benefits are typically realized from the addition
      of APC systems. This paper considers leveraging the control capabilities of
      existing APC systems to minimize the potential impact of a terrorist attack on a
      process plant (e.g., petroleum refinery). Two potential uses of APC are
      described. The first is a conventional application of APC and involves
      automatically moving the process to a reduced operating rate when an attack first
      begins. The second is a non-conventional application and involves reconfiguring
      the APC system to optimize safety rather than economics. The underlying intent in
      both cases is to reduce the demands on the operator to allow focus on situation
      assessment and optimal response planning. An overview of APC is provided along
      with a brief description of the modifications required for the proposed new
      applications of the technology.

PMID- 16298050
TI  - Uptake of phenol from aqueous solutions by adsorption in a Pinus pinaster bark
      packed bed.
AB  - The adsorption of phenol from aqueous solutions using a column packed with pre
      treated Pinus pinaster bark was studied. The influence of the inlet phenol
      concentration (0.01 or 0.1 g/L) and the flow rate (6, 15.6 or 30 mL/min) on the
      breakthrough curves was analysed. An increase in the flow rate, decreased the
      time necessary to reach the breakthrough point and, for the highest inlet
      concentration, the dynamic capacity of the bed, from 7.5 to 0.4 min and from 0.38
      to 0.15 mg phenol/go.d. bark, respectively, at 0.1 g/L. The LUB Design Approach
      was used to determine the equivalent length of unused bed. The lower LUB values,
      which imply a better utilization of the bark bed, were obtained at the higher
      flow rate. A model which considered the effect of axial dispersion was
      successfully used to describe the fixed-bed operation behaviour for the lower
      flow rates. For the lowest inlet phenol concentration, the axial dispersion
      coefficient increased significantly when the flow rate increased.

PMID- 16298049
TI  - Molecular size distribution of dissolved organic matter in water of the Pearl
      River and trihalomethane formation characteristics with chlorine and chlorine
      dioxide treatments.
AB  - River water sample was collected from Guangzhou section of the Pearl River to
      investigate soluble organic fractions and formation of trihalomethane (THMs)
      after chlorine and chlorine dioxide treatments. The water sample was passed
      through Amicon YC-05, YM-1, YM-3, YM-10, YM-30, YM-100 and ZM-500 series
      membranes after a pre-treatment. The molecular weight distribution and the
      specific ultra-violet absorbance (SUVA(254)) of each fraction obtained from
      membrane were analyzed, and these fractions were further disinfected with
      chlorine and chlorine dioxide. The results showed that reverse osmosis (RO)
      fraction contained mainly dissolved organic matter (DOM) from the water sample,
      suggesting that the water has been highly contaminated by anthropogenic
      activities. Meanwhile, the THMs concentration and SUVA(254) increased gradually
      as the molecular weight of the obtained fractions reduced, indicating that the
      low molecular weight DOM was the major THMs precursor in the disinfection process
      with chlorine and chlorine dioxide. The results suggest that THMs in source water
      of Pearl River could be effectively reduced when pollution of human activity is
      greatly controlled. Between the two disinfection processes tested, chlorine
      dioxide produced less THMs than chlorine in this study.

PMID- 16298051
TI  - Adsorption of trace elements from poultry litter by montmorillonite clay.
AB  - Poultry litter (PL) is used as fertilizer on agricultural lands because of its
      high nutrient content. However, the litter also contains trace elements such as
      As, Cd, Cu, Pb, and Zn. On land application of PL, these trace elements may be
      absorbed by crops, leach into groundwater, or enter the aquatic system as run
      off. The objective of this research was to study the effect of the addition of
      montmorillonite clay-mineral (CM) in reducing the release of trace elements from
      PL. Cd, Cu, and Zn showed significant decreases of 29, 34, and 22%, respectively,
      in PL aqueous leachate (compared with the control-PL without CM) on mixing with
      0.05 g CM but no change in As, Co, and Cr concentrations was observed. Lead
      showed a significant increase in PL aqueous leachate on mixing with 0.2 g CM but
      Pb concentration was two orders of magnitude less than in CM aqueous leachate
      alone. On washing, the settled precipitate (PL+CM) in the centrifuge tubes with
      water (desorption study) most of the adsorbed metals (Cd 85%, Cu 61%, and Zn
      100%) were released. The results of this study show that the addition of CM
      resulted in significant adsorption of Cd and Cu from PL.

PMID- 16298052
TI  - Immobilization and encapsulation during vitrification of incineration ashes in a
      coke bed furnace.
AB  - A real-scale coke bed furnace system has been successfully applied to vitrify the
      incineration ashes into glassy slags. The object of this research was to evaluate
      the effect of the system on the immobilization of metal species in the slag.
      Ashes and slag specimens were tested to identify their metal phase distribution
      following a sequential extraction procedure. The mobility of Al, Ca, Cd, Cr, Mg,
      Mn and Pb was noticeably reduced by vitrification. An important implication is
      the reduction of Cr(6+) to Cr(3+) along with its immobilization with this coke
      bed furnace. The Ni and Zn contents were relatively low in slag, indicating that
      their availability of mobile phases in ashes was reduced during vitrification.
      The XRD analyses identified the major crystalline phase in slag as akermanite,
      which is inert and helpful in metal immobilization. The phase distribution
      analysis also contributed to verify that the incorporation of Ca and Mg enhanced
      the encapsulation in the slag matrix. The low oxygen content in slag made the
      structure of silicate resistant to the proton-promoted attack and also enhanced
      the mobility reduction of matrix elements (Ca, Mg and Al) in the moderately
      reducible phase and also contributed to the immobilization of other metal
      species. However, the properties of slag also deserve further studies to ensure
      its long-term stability and safety.

PMID- 16298053
TI  - Managing industrial risk--having a tested and proven system to prevent and assess
      risk.
AB  - Some relatively easy techniques exist to improve the risk picture/profile to aid
      in preventing losses. Today with the advent of computer system resources,
      focusing on specific aspects of risk through systematic scoring and comparison,
      the risk analysis can be relatively easy to achieve. Techniques like these
      demonstrate how working experience and common sense can be combined
      mathematically into a flexible risk management tool or risk model for analyzing
      risk. The risk assessment methodology provided by companies today is no longer
      the ideas and practices of one group or even one company. It is reflective of the
      practice of many companies, as well as the ideas and expertise of academia and
      government regulators. The use of multi-criteria decision making (MCDM)
      techniques for making critical decisions has been recognized for many years for a
      variety of purposes. In today's computer age, the easy accessing and user
      friendly nature for using these techniques, makes them a favorable choice for use
      in the risk assessment environment. The new user of these methodologies should
      find many ideas directly applicable to his or her needs when approaching risk
      decision making. The user should find their ideas readily adapted, with slight
      modification, to accurately reflect a specific situation using MCDM techniques.
      This makes them an attractive feature for use in assessment and risk modeling.
      The main advantage of decision making techniques, such as MCDM, is that in the
      early stages of a risk assessment, accurate data on industrial risk, and failures
      are lacking. In most cases, it is still insufficient to perform a thorough risk
      assessment using purely statistical concepts. The practical advantages towards
      deviating from strict data-driven protocol seem to outweigh the drawbacks.
      Industry failure data often comes at a high cost when a loss occurs. We can
      benefit from this unfortunate acquisition of data through the continuous refining
      of our decisions by incorporating this new information into our assessments. MCDM
      techniques offer flexibility in accessing comparison within broad data sets to
      reflect our best estimation of their importance towards contribution to the risk
      picture. This allows for the accurate determination of the more probable and more
      consequential issues. This can later be refined using more intensive risk
      techniques and the avoidance of less critical issues.

PMID- 16298054
TI  - An empirical model for defluoridation by batch monopolar
      electrocoagulation/flotation (ECF) process.
AB  - Excessive presence of fluoride concentration in community water supplies can
      cause fluorosis that affects the teeth and bones. Batch experiments with
      monopolar aluminium electrodes for fluoride removal were conducted and an
      empirical model is developed using critical parameters such as current
      concentration, electrode distance, and initial fluoride concentration. Fluoride
      ions were removed electrochemically from solution by electrocoagulation/flotation
      (ECF) process. The electrolytic dissolution of aluminium anodes in water produced
      aqueous Al3+ species and hydrogen bubbles at the aluminium cathodes. The fluoride
      removal efficiency increases steadily with increasing current values from 1 to
      2.5 A. In the batch monopolar ECF process, the optimal detention time (dto) was
      found to be 55 min when the operational parameters including initial F-
      concentration, current value, and inter electrode distance were respectively kept
      at 10 mg/l, 1.5 A, and 5 mm. The experimental results showed that the rate
      constant (K) for defluoridation by monopolar ECF process depends on the current
      concentration (I/V), electrode distance (d) and initial fluoride concentration
      (C0). The Al3+/F- mass ratio is found to be not significantly different between
      monopolar and bipolar ECF systems. Overall, the results showed that the
      electrocoagulation technology is an effective process for defluoridation of
      water.

PMID- 16298055
TI  - Biosorption of copper(II) and lead(II) from aqueous solution by chaff in a fixed
      bed column.
AB  - In this article, the ability of chaff to adsorb heavy metal ions from aqueous
      solution was investigated in a fixed-bed column. The effect of important
      parameters, such as the value of pH, the flow rate, the influent concentration of
      solution and the effect of coexistence ions, was studied. Also the
      adsorption/desorption recycles of chaff were shown, and the results indicated
      that chaff could be recycled to remove heavy metal ions. The Thomas model was
      applied to adsorption of copper and lead at different flow rate and different
      influent concentration to predict the breakthrough curves and to determine the
      characteristic parameters of the column useful for process design. The model was
      found suitable for describing the biosorption process of the dynamic behavior of
      the chaff column. All the results suggested that chaff as adsorbent to removal
      heavy metal ions from solution prove efficient, and the rate of biosorption
      process is speedy. Furthermore, the efficiency of adsorption is high. When the
      flow rate was 3.6 ml min(-1) and the influent concentration of copper and lead
      was 14.82 mg l(-1) and 50.12 mg l(-1) respectively, the equilibrium adsorption
      biomass reached 1.98 mg g(-1) and 6.72 mg g(-1), respectively. The competitive
      adsorption for lead and copper was studied. Moreover the total adsorbing
      capability of chaff did not decrease when there were both copper(II) and lead(II)
      in solution.

PMID- 16298056
TI  - Isotherm parameters for basic dyes onto activated carbon: comparison of linear
      and non-linear method.
AB  - Equilibrium sorption experiments were carried out at 305 K with four different
      basic dyes basic red 9 (BR9), basic violet 3 (BV3), basic brown 1 (BB1) and basic
      violet 10 (BV10) onto activated carbon. The isotherm parameters were estimated
      linear and non-linear regression analysis. Non-linear method was found to be more
      appropriate method for estimating the isotherm parameters. The sorption capacity
      of activated carbon to uptake cationic dye ions in the increasing order was given
      by: BR9 (131 mg/g)< BV3 (247 mg/)< BV10 (259 mg/)< BB1 (404 mg/g).

PMID- 16298057
TI  - External inferior colliculus integrates trigeminal and acoustic information: unit
      responses to trigeminal nucleus and acoustic stimulation in the guinea pig.
AB  - The external nucleus of the inferior colliculus (ICx) receives ascending
      projections from both auditory and somatosensory nuclei. In the guinea pig, both
      the spinal trigeminal nucleus (TN) and the cochlear nucleus converge in the
      ventrolateral region of ICx. We investigated the function of trigeminal
      collicular pathways by electrically stimulating the TN while recording unit
      responses from ICx. Pairing electrical stimulation with acoustic stimuli allowed
      us to investigate the function of converging auditory and somatosensory inputs,
      i.e. multisensory integration. Unit responses were recorded from ICx using a
      multi channel, single shank electrode. Electrical stimulation of the TN produced
      small changes above or below spontaneous rate, but resulted in significant
      suppression or enhancement of sound-evoked responses. Multisensory integration
      has been demonstrated in the dorsal cochlear nucleus (DCN), superior colliculus
      and sensory cortices and may play a role in plasticity that occurs after sensory
      deprivation.

PMID- 16298058
TI  - Efferent connections of the main olfactory bulb in the opossum (Monodelphis
      domestica): a characterization of the olfactory entorhinal cortex in a marsupial.
AB  - Olfactory projections have been investigated for decades, but few reports using
      modern, sensitive neural tracers are available. In marsupials, only lesion
      degeneration studies exist and they are restricted to the genera Didelphis and
      Trichosurus. Some of the territories described as olfactory-recipient such as the
      upper portion of the rhinal fissure and the vomeronasal amygdala are, however,
      controversial. Also, the characterization of the olfactory portion of the
      entorhinal cortex is far from clear in acallosal mammals. The present report
      investigates, using biotinylated dextran-amine, the olfactory connections in the
      short-tailed opossum (Monodelphis domestica) and characterizes the olfactory
      portion of the entorhinal cortex in non-placental mammals. The data indicate that
      olfactory projections do not reach the upper portion of the rhinal fissure, but
      partially end in the vomeronasal amygdala, i.e., the medial and posteromedial
      cortical amygdaloid nuclei; thus, although olfactory and vomeronasal system have
      largely segregated outputs, areas of overlap should be restudied. The olfactory
      portion of the entorhinal cortex is much larger than previously described,
      extending up to the occipital pole of the cerebral hemisphere. Collectively,
      these data contribute to our understanding of the organization of the hippocampal
      formation in marsupials.

PMID- 16298059
TI  - Categorising the severity of neck pain: establishment of cut-points for use in
      clinical and epidemiological research.
AB  - Grading pain intensity scales into simple categories provides useful information
      for both clinicians and epidemiologists and methods to classify pain severity for
      numerical rating scales have been recommended. However, the establishment of cut
      points is still in its infancy and little is known as to whether cut-points are
      affected by age or gender. The objectives of this paper were to establish optimal
      cut-points in pain severity in individuals with neck pain (NP) and to investigate
      if the cut-points were influenced by gender, age, and NP duration. Data from the
      population-based ;Funen Neck and Chest Pain Study' was used. Univariate and
      multivariate analyses of variance were performed to calculate optimal single and
      double cut-points for three different pain intensity scores within the past 2
      weeks relative to two neck disability scales (;global assessment of NP' and the
      ;Copenhagen Neck Functional Disability Scale'). The two disability scales showed
      small differences in optimal cut-points. Furthermore, cut-points changed for each
      of the three pain intensity scales. Only small gender differences in cut-points
      were seen and no specific trend was noted in either single or double cut-points
      in different age groups. The cut-points were almost identical for acute,
      subacute, and chronic NP. This paper has implications for understanding the
      impact of using different pain intensity scales and provides reference cut-points
      in NP for use in future clinical and epidemiological research.

PMID- 16298061
TI  - A randomized, double-blind, placebo-controlled trial of duloxetine in the
      treatment of women with fibromyalgia with or without major depressive disorder.
AB  - This was a 12-week, randomized, double-blind, placebo-controlled trial to assess
      the efficacy and safety of duloxetine, a selective serotonin and norepinephrine
      reuptake inhibitor, in 354 female patients with primary fibromyalgia, with or
      without current major depressive disorder. Patients (90% Caucasian; mean age,
      49.6 years; 26% with current major depressive disorder) received duloxetine 60 mg
      once daily (QD) (N=118), duloxetine 60 mg twice daily (BID) (N=116), or placebo
      (N=120). The primary outcome was the Brief Pain Inventory average pain severity
      score. Response to treatment was defined as >or=30% reduction in this score.
      Compared with placebo, both duloxetine-treated groups improved significantly more
      (P<0.001) on the Brief Pain Inventory average pain severity score. A
      significantly higher percentage of duloxetine-treated patients had a decrease of
      >or=30% in this score (duloxetine 60 mg QD (55%; P<0.001); duloxetine 60 mg BID
      (54%; P=0.002); placebo (33%)). The treatment effect of duloxetine on pain
      reduction was independent of the effect on mood and the presence of major
      depressive disorder. Compared with patients on placebo, patients treated with
      duloxetine 60 mg QD or duloxetine 60 mg BID had significantly greater improvement
      in remaining Brief Pain Inventory pain severity and interference scores,
      Fibromyalgia Impact Questionnaire, Clinical Global Impression of Severity,
      Patient Global Impression of Improvement, and several quality-of-life measures.
      Both doses of duloxetine were safely administered and well tolerated. In
      conclusion, both duloxetine 60 mg QD and duloxetine 60 mg BID were effective and
      safe in the treatment of fibromyalgia in female patients with or without major
      depressive disorder.

PMID- 16298062
TI  - The significant other version of the Pain Catastrophizing Scale (PCS-S):
      preliminary validation.
AB  - Researchers have hypothesized that pain catastrophizing has a social function.
      Although work has focused on the catastrophizing of individuals with chronic pain
      (ICPs), little is known about the pain catastrophizing of their significant
      others. The purpose of this study was to test the validity of a revised version
      of the original PCS [Sullivan MJL, Bishop S, Pivik J. The pain catastrophizing
      scale: development and validation. Psychol Assess 1995; 7: 432-524.] in which
      individuals were instructed to report on their own catastrophizing about their
      significant other's pain. In Study 1, a confirmatory factor analysis was
      conducted to determine the factor structure of the PCS-Significant Other (PCS-S)
      in a diverse sample of university undergraduates (n=264). An oblique second-order
      3-factor model with two cross-loadings provided the best fit and this model was
      invariant across gender and racial groups. This factor structure was cross
      validated in Study 2 with a second sample of university undergraduates (n=213).
      Results indicated that the 3-factor structure with two cross-loadings was a
      viable model of significant others' pain catastrophizing across gender and racial
      groups. In Study 3, this factor structure was replicated and the content validity
      of the PCS-S was examined in a sample of adult ICPs and their spouses (n=111).
      Spouse catastrophizing was related to ICP pain severity and interference as well
      as both spouses' depressive symptoms. In addition, ICPs were at a greater risk
      for psychological distress when both spouses had higher levels of
      catastrophizing. The PCS-S has the potential to be a useful and valid measure of
      pain catastrophizing in the significant others of ICPs.

PMID- 16298063
TI  - Risk factors for acute pain and its persistence following breast cancer surgery.
AB  - Although more severe acute postoperative pain increases the risk of chronic pain
      following breast cancer surgery, few studies have examined the characteristics of
      patients who develop greater acute pain. To identify risk factors for acute pain
      and its persistence one month following breast cancer surgery, a sample of 114
      women scheduled for breast cancer surgery was assessed preoperatively for
      demographic, clinical, and emotional functioning variables that were hypothesized
      to be associated with acute pain severity. Clinically meaningful postoperative
      pain was assessed at follow-up interviews 2, 10, and 30 days after surgery. In
      univariate analyses, the risk of clinically meaningful acute pain was increased
      among women who were younger, unmarried, had more invasive surgeries, and had
      greater preoperative emotional distress. In multiple logistic regression
      analyses, greater preoperative anxiety was the only variable that made an
      independent contribution to predicting clinically meaningful acute pain at 2 days
      after surgery whereas younger age, being unmarried, and preoperative anxiety each
      made an independent contribution to predicting clinically meaningful acute pain
      that persisted from 2 to 30 days after surgery. These results increase
      understanding of neurobiologic mechanisms and psychosocial processes that
      contribute to the development of acute pain following breast cancer surgery and
      have implications for the development of interventions to prevent it.

PMID- 16298064
TI  - Headache in schoolchildren: association with other pain, family history and
      psychosocial factors.
AB  - Limited information exist about associations between different headache types and
      other pains, family history of pain, and psychosocial factors among children from
      the general population suffering from less severe headache. We interviewed 130
      schoolchildren together with a parent to find out whether such factors differ
      between children with mainly infrequent and moderate migraine or tension-type
      headache as compared to those without primary headache. Children with headache,
      especially those with migraine reported other pains and physical symptoms more
      frequently than children without primary headache. Coherently, parents of
      children suffering from migraine reported their children to have significantly
      more somatic symptoms than parents of children without primary headache. In
      addition, first-degree relatives of children with headache suffered from more
      migraine, other pains, and physical symptoms compared with first-degree relatives
      of children without primary headache. Children with migraine visited the school
      nurse, used medication and were absent from school because of headache more often
      than those with tension-type headache. Few other differences in psychosocial
      factors were found between the three groups. Migraine among first-degree
      relatives and the total sum of physical symptoms in children were the strongest
      predictors of headache in logistic regression analysis. It is concluded that in
      schoolchildren with mainly infrequent and moderate headache, pain and physical
      symptoms cluster within individuals as well as their families, however,
      psychological and social problems are uncommon.

PMID- 16298065
TI  - Characterizing individual differences in heat-pain sensitivity.
AB  - Heat induced pain has been shown to follow a positively accelerating power
      function for groups of subjects, yet the extent to which this applies to
      individual subjects is unknown. Statistical methods were developed for assessing
      the goodness of fit and reliability of the power function for data from
      individual subjects with the aim of using such functions for characterizing
      individual differences in heat-pain sensitivity. 175 subjects rated ascending and
      random series of contact heat stimuli with visual analogue scales for pain
      intensity (VAS-I) and unpleasantness (VAS-A). Curve fitting showed excellent
      model fit. Substitution of model estimates in place of observed VAS scores
      produced minimal bias in group means, about 0.3 VAS units in the ascending series
      and 1.0 in the random series, on a 0-100 scale. Individual power function
      exponents were considerably higher for the ascending than for the random series
      and somewhat higher for VAS-A than for VAS-I (means: ascending VAS-I=9.04, VAS
      A=9.80; random VAS-I=4.95, VAS-A=5.67). The reliability of VAS estimates was high
      (>==.93), and for the ascending series it remained so when extrapolating 4
      degrees C beyond the empirical range. Exponent reliability was high for the
      ascending series (VAS-I=.92; VAS-A=.91), but considerably lower for the random
      series (VAS-I=.69; VAS-A=.71). Individual differences constituted 60% of the
      total variance in pain ratings, whereas stimulus temperature accounted for only
      40%. This finding underscores the importance of taking individual differences
      into account when performing pain studies.

PMID- 16298066
TI  - Regular use of prescribed opioids: association with common psychiatric disorders.
AB  - Use of opioids for chronic non-cancer pain is increasing, but the clinical
      epidemiology and standards of care for this practice are poorly defined.
      Psychiatric disorders are associated with increased physical symptoms and may be
      associated with opioid use. We performed a secondary analysis of cross-sectional
      data from the Health Care for Communities (HCC) survey conducted in 1997-1998
      (N=9279) to determine the association of psychiatric disorders and self-reported
      regular use of prescribed opioids within the past year. Regular prescription
      opioid use was reported by 282 (3%) respondents. In unadjusted logistic
      regression models, respondents with common mental disorders in the past year
      (major depression, dysthymia, generalized anxiety disorder, or panic disorder)
      were more likely to report regular prescription opioid use than those without any
      of these disorders (OR=6.15, 95% CI=4.13, 9.14, P< 0.001). Respondents reporting
      problem drug use (OR=4.75, 95% CI=2.52, 8.94, P<0.001), or problem alcohol use
      (OR=1.89, 95% CI=1.03, 3.40, P=.041) reported higher rates of prescribed opioid
      use than those without problem use. In multivariate logistic regression models
      controlling for demographic and clinical variables, the presence of a common
      mental disorder remained a significant predictor of prescription opioid use
      (OR=3.15, 95% CI=1.69, 5.88, P<0.001), among individuals reporting low pain
      interference (N=8307); but not (OR=1.27, n.s.) among those reporting high pain
      interference (N=972). Depressive, anxiety and drug abuse disorders are associated
      with increased use of regular opioids in the general population. Depressive and
      anxiety disorders are more common and more strongly associated with prescribed
      opioid use than drug abuse disorders.

PMID- 16298068
TI  - Reduced reactivity and enhanced negative feedback sensitivity of the hypothalamus
      pituitary-adrenal axis in chronic whiplash-associated disorder.
AB  - Dysregulations of the hypothalamus-pituitary-adrenal (HPA) axis have been
      discussed as a physiological substrate of chronic pain and fatigue. The aim of
      the study was to investigate possible dysregulations of the HPA axis in chronic
      whiplash-associated disorder (WAD). In 20 patients with chronic WAD and 20
      healthy controls, awakening cortisol responses as well as a short circadian free
      cortisol profile were assessed before and after administration of 0.5mg
      dexamethasone. In comparison to the controls, chronic WAD patients had attenuated
      cortisol responses to awakening, normal cortisol levels during the day, and
      showed enhanced and prolonged suppression of cortisol after the administration of
      0.5mg dexamethasone. Dysregulations of the HPA axis in terms of reduced
      reactivity and enhanced negative feedback suppression exist in chronic WAD. The
      observed endocrine abnormalities could serve as a systemic mechanism of symptoms
      experienced by chronic WAD patients.

PMID- 16298067
TI  - Mechanisms underlying enhanced P2X receptor-mediated responses in the neuropathic
      pain state.
AB  - P2X3 and P2X2/3 receptors in dorsal root ganglia (DRG) appear to participate in
      producing nociceptive responses after nerve injury. However, the mechanisms
      underlying the receptor-mediated nociception in the neuropathic state remain
      unclear. Using spared nerve injury (SNI) rats, we found that allodynic and
      nocifensive (flinch) behavioral responses developed after injury can be reversed
      by P2X receptor antagonists, indicating an involvement of P2X receptors.
      Immunocytochemical studies revealed that P2X3 receptors are expressed in small
      and medium but rarely in large DRG neurons of both normal and SNI rats. Thus,
      contrary to the conventional view that only large A beta cells mediate allodynia,
      small and medium cells are intimately involved in P2X3 receptor-mediated
      allodynia. Measuring ATP levels in the subcutaneous space of the rat paw, we
      showed that ATP release does not change after SNI. On the other hand, the P2X
      receptor agonist, alpha beta-methylene ATP produces 3.5-fold larger flinch
      responses at a 8.0-fold lower dose. Thus, sensitization of P2X3 receptors rather
      than a change in ATP release is responsible for the neuropathic pain behaviors.
      We further demonstrated that sensitization of P2X3 receptors arises from an
      increase in receptor function. ATP-induced P2X3 receptor-mediated currents in DRG
      neurons is 2.5-fold larger after SNI. The expression of P2X3 receptors on the
      cell membrane is significantly enhanced while the total expression of P2X3
      receptors remained unchanged. Thus, the enhancement of trafficking of P2X3
      receptors is likely an important mechanism contributing to the increase in
      receptor function after nerve injury.

PMID- 16298070
TI  - Assessment of nociception in acrylamide-induced neuropathy in rats.
AB  - Acrylamide was intraperitoneally administered to male Sprague-Dawley rats at four
      different doses (5, 10, 20 and 30 mg/kg) three times a week for 5 consecutive
      weeks. Because of motor dysfunction, the 30 mg/kg dose was not used for
      behavioral pain tests. Clinical status remained good throughout the experiment
      and no motor deficit was observed at the other doses. We showed that acrylamide
      administration at low doses and cumulative dose (CD) range of 35-140 mg/kg
      produced mechanical allodynia and rapid, marked heat (42 degrees C) and cold (10
      degrees C) allodynia after tail immersion test. Mechanical and thermal
      hyperalgesia appeared after higher cumulative doses (70-280 mg/kg), except for
      cold (4 degrees C) hyperalgesia (20-80 mg/kg). All the modifications persisted
      throughout all study, except the mechanical hyperalgia. All the cumulative doses
      tested were lower than those generally reported to induce motor dysfunction
      (CD>250 mg/kg), confirming that CD may be considered to be a suitable index in
      assessing neurological signs and suggesting that early detection of acrylamide
      neurotoxicity would be possible using the sensory tests, especially those for
      detecting allodynia thresholds.

PMID- 16298069
TI  - Does medication overuse headache represent a behavior of dependence?
AB  - Medication overuse is relatively common in patients with frequent headache. To
      explore the prevalence of patients who meet the criteria for substance dependence
      in Diagnostic and Statistical Manual of Mental Disorders, Edition IV (DSM-IV),
      and to identify variables of substance dependence among patients with chronic
      daily headache, we recruited consecutive patients with chronic daily headache at
      a headache clinic from November 1999 to June 2004. Each patient completed a
      headache intake form, a dependence questionnaire modified from DSM-IV, and the
      Hospital Anxiety and Depression Scale (HADS). The presence of probable medication
      overuse headache (pMOH) was defined on the basis of the International
      Classification of Headache Disorders, 2nd edition, 2004. A total of 1,861
      patients with chronic daily headache (1,369 women, 492 men; mean age, 49.6+/-15.4
      years) were recruited. Almost half (895/1,861, 48%) met criteria of pMOH, and 606
      of these patients (606/895, 68%) met three of five DSM-IV substance dependence
      criteria. In contrast, only 191 of 968 patients without pMOH (20%) met the DSM-IV
      criteria (OR=8.6, [7.0-10.6], chi-square test, P<0.001). Patients who fulfilled
      DSM-IV criteria of dependence had higher numbers of physician appointments in the
      past year. Multivariate logistic regression analyses revealed that migraine
      headache, frequent physician consultation, intensity of headache, and presence of
      a higher anxiety score were significant independent variables for substance
      dependence. Among patients with chronic daily headache, pMOH was associated with
      behaviors of substance dependence.

PMID- 16298071
TI  - Peripheral inflammation induces up-regulation of TRPV2 expression in rat DRG.
AB  - The transient receptor potential vanilloid subfamily member 2 (TRPV2) is a cation
      channel activated by temperatures above 52 degrees C. To analyze the contribution
      of TRPV2 to the development of inflammation-induced hyperalgesia, the expression
      of TRPV2 in primary sensory neurons was analyzed after intraplantar injection of
      complete Freund's adjuvant (CFA). Using specific antibodies, an increase in TRPV2
      expressing neurons was identified after inflammation. TRPV2 expression is
      concentrated in a subset of medium-sized dorsal root ganglion neurons,
      independent of transient receptor potential vanilloid subfamily member 1 (TRPV1)
      expression. A similar distribution of TRPV2 was observed after inflammation.
      Intraplantar injection of nerve growth factor increased TRPV1 expression but not
      TRPV2, suggesting that induction of TRPV2 expression is driven by a mechanism
      distinct from that for TRPV1. Heat hyperalgesia assessment after chemical
      desensitization of TRPV1 by resiniferatoxin demonstrates a possible role for
      TRPV2 in inflammation at high temperatures (>56 degrees C). These results suggest
      that TRPV2 upregulation contributes to peripheral sensitization during
      inflammation and is responsible for pain hypersensitivity to noxious high
      temperature stimuli.

PMID- 16298072
TI  - High-quality evidence in oncology from 19 May to 9 June 2005: a summary.

PMID- 16298073
TI  - The emerging role of DNA repair proteins as predictive, prognostic and
      therapeutic targets in cancer.
AB  - Advanced cancer is the second leading cause of death in the western world.
      Chemotherapy and radiation are the two main treatment modalities currently
      available to improve patient outcomes, but treatment related toxicity and the
      emergence of resistance limit their effectiveness. Hence there is an urgent need
      to develop novel treatment strategies. Rapid advances in cancer biology have
      identified key pathways involved in the repair of DNA damage induced by
      chemotherapeutic agents and irradiation. Efficient DNA repair in the cancer cell
      is an important mechanism for therapeutic resistance. Up to 130 genes have been
      identified that are associated with human DNA repair. Several of these proteins
      are emerging as important predictive and prognostic factors in solid tumours.
      Inhibition of DNA repair has the potential to enhance the efficacy of currently
      available DNA damaging agents. In recent years, several promising drug targets
      have been identified and novel drugs synthesised that target specific DNA repair
      proteins. These agents have shown impressive anti-cancer effects in preclinical
      studies in combination with chemotherapy or irradiation. Their role in human
      cancer is now being investigated in early phase clinical trials in combination
      with chemotherapy. MGMT inhibitors, PARP inhibitors and methoxyamine are
      currently in early stages of clinical development. Innovative clinical trial
      designs are essential to evaluate the potential of DNA repair inhibitor in cancer
      therapy.

PMID- 16298074
TI  - Bortezomib, a novel proteasome inhibitor, in the treatment of hematologic
      malignancies.
AB  - Proteasome inhibition is a novel approach to treating malignancy, and bortezomib
      is the first proteasome inhibitor in this class to be approved for clinical use.
      In preclinical studies, bortezomib caused cell cycle arrest and apoptosis in
      myeloma and lymphoma cell lines as well as in other neoplastic cell types. Phase
      I clinical trials established an optimal dosing strategy and demonstrated a
      manageable toxicity profile. Cyclical thrombocytopenia and peripheral neuropathy,
      which generally abate after cessation of treatment, are the most clinically
      significant toxicities. Two phase II trials, SUMMIT and CREST, demonstrated
      impressive activity with bortezomib 1.3 mg/m2 monotherapy in relapsed and
      refractory myeloma, with an impressive 35% response rate
      (complete+partial+minimal responses) in SUMMIT and a 50% response rate in CREST,
      using the rigorous European Group for Blood and Marrow Transplantation criteria.
      A recently completed phase III trial showed the significant clinical benefits of
      bortezomib over high-dose dexamethasone in patients with relapsed myeloma.
      Results of ongoing trials with bortezomib in the first-line treatment of myeloma
      have been extremely encouraging and have demonstrated the benefit of using
      bortezomib as part of an induction regimen prior to stem cell transplantation.
      Importantly, two clinical trials with bortezomib as monotherapy in refractory non
      Hodgkin's lymphoma have shown impressive response rates, particularly in
      aggressive mantle cell lymphoma.

PMID- 16298075
TI  - Eye movements evoked by electrical microstimulation of the mesencephalic
      reticular formation in goldfish.
AB  - Anatomical studies in goldfish show that the tectofugal axons provide a large
      number of boutons within the mesencephalic reticular formation. Electrical
      stimulation, reversible inactivation and cell recording in the primate central
      mesencephalic reticular formation have suggested that it participates in the
      control of rapid eye movements (saccades). Moreover, the role of this tecto
      recipient area in the generation of saccadic eye movements in fish is unknown. In
      this study we show that the electrical microstimulation of the mesencephalic
      reticular formation of goldfish evoked short latency saccadic eye movements in
      any direction (contraversive or ipsiversive, upward or downward). Movements of
      the eyes were usually disjunctive. Based on the location of the sites from which
      eye movements were evoked and the preferred saccade direction, eye movements were
      divided into different groups: pure vertical saccades were mainly elicited from
      the rostral mesencephalic reticular formation, while oblique and pure horizontal
      were largely evoked from middle and caudal mesencephalic reticular formation
      zones. The direction and amplitude of pure vertical and horizontal saccades were
      unaffected by initial eye position. However the amplitude, but not the direction
      of most oblique saccades was systematically modified by initial eye position. At
      the same time, the amplitude of elicited saccades did not vary in any consistent
      manner along either the anteroposterior, dorsoventral or mediolateral axes (i.e.
      there was no topographic organization of the mesencephalic reticular formation
      with respect to amplitude). In addition to these groups of movements, we found
      convergent and goal-directed saccades evoked primarily from the anterior and
      posterior mesencephalic reticular formation, respectively. Finally, the metric
      and kinetic characteristics of saccades could be manipulated by changes in the
      stimulation parameters. We conclude that the mesencephalic reticular formation in
      goldfish shares physiological functions that correspond closely with those found
      in mammals.

PMID- 16298076
TI  - Intracarotid transplantation of bone marrow stromal cells increases axon-myelin
      remodeling after stroke.
AB  - The present study investigates the induction of axon and myelin remodeling as a
      possible mechanism by which treatment of stroke with bone marrow stromal cells
      improves neurological functional recovery. Adult male Wistar rats were subjected
      to 2 h of middle cerebral artery occlusion, followed by an injection of 2 x 10(6)
      rat bone marrow stromal cells or phosphate-buffered saline into the internal
      carotid artery 24 h later. Animals were killed at 28 days after stroke.
      Functional tests, histo- and immunohistochemical staining were performed.
      Significant functional recovery was found after bone marrow stromal cell
      administration in all the three tests performed (modified neurological severity
      score, adhesive-removal and corner tests). Bone marrow stromal cell treatment
      markedly increased vessel sprouting, synaptophysin expression and NG2 positive
      cell numbers and density in the cortical peri-infarct area. In bone marrow
      stromal cell-treated rats, the number of Ki-67 positive proliferating cells and
      oligodendrocyte precursor cells in the corpus callosum increased significantly in
      concert with the enhancement of the areas of the corpus callosum in both
      hemispheres. These results suggest that bone marrow stromal cells facilitate
      axonal sprouting and remyelination in the cortical ischemic boundary zone and
      corpus callosum, which may underlie neurological functional improvement caused by
      bone marrow stromal cell treatment.

PMID- 16298078
TI  - Adult and in utero exposure to cocaine alters sensitivity to the Parkinsonian
      toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
AB  - Cocaine abuse is a significant problem in the United States, including its use by
      approximately 1% of pregnant women. Cocaine acts as an indirect agonist of
      dopamine at the dopamine transporter, resulting in the presence of excess
      dopamine in the synapse. Since synaptic dopamine can rapidly oxidize to form free
      radicals, it was hypothesized that exposure to this drug might produce damage in
      dopaminergic systems such as the substantia nigra pars compacta, damage to which
      is a hallmark of Parkinson's disease. To test this hypothesis we exposed mice
      both in utero and as adults to cocaine and examined its effects on the
      nigrostriatal system. We found that exposure to cocaine both in utero or as
      adults did not affect substantia nigra cell number, but did make these neurons
      more susceptible to the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine. We also found long-lasting changes in D2 receptor mRNA levels
      as well as changes in the monoamine transport system and several growth factors.
      This work suggests that use of cocaine might be a predisposing factor for
      development of Parkinson's disease in both adults exposed chronically as well as
      in individuals exposed prenatally.

PMID- 16298077
TI  - Oxygen-induced mitochondrial biogenesis in the rat hippocampus.
AB  - The hypothesis that damage to mitochondrial DNA by reactive oxygen species
      increases the activity of nuclear and mitochondrial transcription factors for
      mitochondrial DNA replication was tested in the in vivo rat brain. Mitochondrial
      reactive oxygen species generation was stimulated using pre-convulsive doses of
      hyperbaric oxygen and hippocampal mitochondrial DNA content and neuronal and
      mitochondrial morphology and cell proliferation were evaluated at 1, 5 and 10
      days. Gene expression was subsequently evaluated to assess nuclear and
      mitochondrial-encoded respiratory genes, mitochondrial transcription factor A,
      and nuclear respiratory transcription factors-1 and -2. After 1 day, a
      mitochondrial DNA deletion emerged involving Complex I and IV subunit-encoding
      regions that was independent of overt neurological or cytological O(2) toxicity,
      and resolved before the onset of cell proliferation. This damage was attenuated
      by blockade of neuronal nitric oxide synthase. Compensatory responses were found
      in nuclear gene expression for manganese superoxide dismutase, mitochondrial
      transcription factor A, and nuclear respiratory transcription factor-2. Enhanced
      nuclear respiratory transcription factor-2 binding activity in hippocampus was
      accompanied by a nearly three-fold boost in mitochondrial DNA content over 5
      days. The finding that O(2) activates regional mitochondrial DNA transcription,
      replication, and mitochondrial biogenesis in the hippocampus may have important
      implications for maintaining neuronal viability after brain injury.

PMID- 16298079
TI  - Changes in immediate early gene expression in the rat brain after unilateral
      lesions of the hippocampus.
AB  - Activity of the immediate early genes c-fos and zif268 was compared across
      hemispheres in rats with unilateral, excitotoxic lesions of the hippocampus
      (dentate gyrus and CA fields 1-4). Counts of the protein products of these genes
      were made shortly after rats performed a test of spatial working memory in the
      radial-arm maze, a task that is sensitive to bilateral lesions of the
      hippocampus. Unilateral hippocampal lesions produced evidence of widespread
      hypoactivity. Significant reductions in immediate early gene counts were observed
      within all three anterior thalamic nuclei, as well as the entorhinal, perirhinal,
      and postrhinal cortices, and much of the subicular complex. In contrast, no
      observable changes were detected in the anterior cingulate, infralimbic or
      prelimbic cortices, as well as several amygdala nuclei, even though many of these
      regions receive projections from the subiculum. Instead, the immediate early gene
      changes were closely linked to sites that are thought to be required for
      successful task performance, with both immediate early genes giving similar
      patterns of results. The findings support the notion that the anterior thalamic
      nuclei, hippocampus, and parahippocampal cortices form the key components of an
      interdependent neuronal network involved in spatial mnemonic processing.

PMID- 16298080
TI  - Endothelin-1 enhances capsaicin-evoked intracellular Ca2+ response via activation
      of endothelin a receptor in a protein kinase Cepsilon-dependent manner in dorsal
      root ganglion neurons.
AB  - Increasing evidence indicates that endothelin-1 has a role for peripheral
      nociceptive signaling in animals and humans. However, the mechanisms of the
      nociceptive effects of endothelin-1 have not been fully understood. The current
      study investigated the effects of endothelin-1 on the capsaicin-evoked
      intracellular Ca2+ response of cultured adult mice dorsal root ganglion neurons.
      Dorsal root ganglia were harvested from adult male C57B6N mice and were cultured.
      With a digital image analysis system, we detected the [Ca2+]i image of cultured
      dorsal root ganglion cells after loading with Fura-2 acetoxymethyl. In addition,
      co-localization of protein kinase Cepsilon with transient receptor potential V1
      and the translocation of protein kinase Cepsilon were investigated using
      immunohistochemical methods. Endothelin-1 (10 nM) enhanced an increase in [Ca2+]i
      by capsaicin (10 nM) from 87.6+/-11.6 nM to 414.8+/-62.3 nM (71 of 156 neurons).
      The inhibition of endothelin A receptor (BQ-123) significantly suppressed the
      enhancing effect of endothelin-1. In addition, a nonselective protein kinase C
      inhibitor (bisindolylmaleimide I) significantly suppressed the enhancing effect
      of endothelin-1. A myristoyl-tagged membrane-permeant-protein kinase Cepsilon V1
      2 inhibitory peptide also significantly suppressed the enhancing effect of
      endothelin-1. In the immunocytochemical study, protein kinase Cepsilon
      immunoreactivity was found in most of transient receptor potential V1-positive
      neurons. After endothelin-1 application, protein kinase Cepsilon immunoreactivity
      was observed to be translocated from the cytosol to the cell membrane in
      transient receptor potential V1-positive neurons. Our results indicate that
      endothelin-1 enhances the response of dorsal root ganglion neurons to capsaicin
      in a protein kinase Cepsilon-dependent manner. Our findings may lead to a new
      strategy to treat pain associated with endothelin-1.

PMID- 16298081
TI  - Noradrenergic modulation of cognitive function in rat medial prefrontal cortex as
      measured by attentional set shifting capability.
AB  - The brain noradrenergic system is thought to facilitate neuronal processes that
      promote behavioral activation, alertness, and attention. One region in which
      norepinephrine may exert such effects is the medial prefrontal cortex, which has
      been implicated in many cognitive functions including arousal, attention,
      motivation, working memory, response inhibition, and behavioral flexibility. The
      present study addressed the modulatory influence of noradrenergic
      neurotransmission in medial prefrontal cortex on cognitive function in rats, as
      measured by performance in an attentional set shifting task. In experiment 1, we
      tested effects of increasing and decreasing brain noradrenergic neurotransmission
      by systemic administration of the alpha2-adrenergic autoreceptor antagonist and
      agonist drugs, atipamezole and clonidine, respectively. Atipamezole pretreatment
      significantly improved performance on the stages of the attentional task
      requiring an extradimensional shift in attention, and those involving stimulus
      reversals, whereas clonidine had no effect at any stage. In experiment 2, we then
      tested effects of microinjecting alpha1- or beta-adrenergic receptor antagonists
      into medial prefrontal cortex on the enhancement of performance on the
      extradimensional task produced by atipamezole. The atipamezole-induced
      enhancement of performance on the extradimensional set shifting task was blocked
      by alpha1-, but not beta-adrenergic receptor antagonists in medial prefrontal
      cortex. Neither antagonist alone had any effect on extradimensional set shift
      performance in the absence of atipamezole-induced enhancement. These results
      indicate that elevating noradrenergic activity at alpha1-receptors in medial
      prefrontal cortex facilitates cognitive performance of rats in an attentional set
      shifting task, which may contribute to the role of norepinephrine in behavioral
      state changes such as arousal, or to the beneficial cognitive effects of
      psychotherapeutic drugs that target noradrenergic neurotransmission.

PMID- 16298082
TI  - Stimulus-evoked release of neuropeptides is enhanced in sensory neurons from mice
      with a heterozygous mutation of the Nf1 gene.
AB  - Neurofibromatosis type I is a common autosomal dominant disease characterized by
      formation of multiple benign and malignant tumors. People with this disorder also
      experience chronic pain, which can be disabling. Neurofibrinomin, the protein
      product of the NF1 gene (neurofibromin gene (human)), is a guanosine triphosphate
      activating protein for p21(ras). Loss of NF1 results in an increase in activity
      of the p21(ras) transduction cascade. Because of the growing evidence suggesting
      involvement of downstream components of the p21(ras) transduction cascade in the
      sensitization of nociceptive sensory neurons, we examined the stimulus-evoked
      release of the neuropeptides, substance P and calcitonin gene-related peptide,
      from primary sensory neurons of mice with a mutation of the Nf1 gene
      (neurofibromin gene (mouse)) (Nf1+/-). Measuring immunoreactive substance P and
      immunoreactive calcitonin gene-related peptide by radioimmunoassay, we
      demonstrated that capsaicin-stimulated release of neuropeptides is three to five
      fold higher in spinal cord slices from Nf1+/- mice than from wildtype mouse
      tissue. In addition, the potassium and capsaicin-stimulated release of
      immunoreactive calcitonin gene-related peptide from cultures of sensory neurons
      isolated from Nf1+/- mice was more than double that from cultures of wildtype
      neurons. Treatment of wildtype sensory neurons with nerve growth factor for 5-7
      days mimicked the enhanced stimulus-evoked release observed from the Nf1+/-
      neurons. When nerve growth factor was removed 48 h before conducting release
      experiments, nerve growth factor-induced augmentation of immunoreactive
      calcitonin gene-related peptide release from Nf1+/- neurons was more pronounced
      than in Nf1+/- sensory neurons that were treated with nerve growth factor
      continuously for 5-7 days. Thus, sensory neurons from mice with a heterozygous
      mutation of the Nf1 gene that is analogous to the human disease neurofibromatosis
      type I, exhibit increased sensitivity to chemical stimulation. This augmented
      responsiveness may explain the abnormal pain sensations experienced by people
      with neurofibromatosis type I and suggests an important role for guanosine
      triphosphate activating proteins, in the regulation of nociceptive sensory neuron
      sensitization.

PMID- 16298083
TI  - GABA(B) receptor-mediated modulation of cutaneous input at the cuneate nucleus in
      anesthetized cats.
AB  - This study examined the modulatory influence exerted by GABA(B) receptors on the
      transmission of cutaneous afferent input to cuneate nucleus neurons in
      anesthetized cats. Electrical stimulation at the center of a receptive field
      activated cuneate nucleus cells at latencies of < or = 7 ms whereas stimulation
      at neighboring sites (receptive field edge) increased the response latency.
      Extracellular recording combined with microiontophoresis demonstrated that
      GABA(B) receptors are tonically active. Blockade of GABA(B) receptors prolonged
      sensory-evoked response durations and decreased times of occurrence of successive
      bursts whereas the agonist baclofen suppressed both these effects. Ejection of
      baclofen delayed the evoked response from the receptive field edge with respect
      to the receptive field center response and inhibited responses from the receptive
      field edge more effectively than responses from the receptive field center. From
      these results it is concluded that activation of GABA(B) receptors precludes
      cuneate cells from reaching firing threshold when afferent inputs are weak,
      spatially modulate cuneate nucleus excitability, play a major role in temporal
      pattern of discharges, and shape cutaneous receptive fields.

PMID- 16298084
TI  - The enhancement of cell adherence and inducement of neurite outgrowth of dorsal
      root ganglia co-cultured with hyaluronic acid hydrogels modified with Nogo-66
      receptor antagonist in vitro.
AB  - Hyaluronic acid hydrogels modified with polyclonal anti-Nogo-66 receptor antibody
      were developed in order to promote regeneration in the injured CNS. These
      modified hydrogels were intended not only to deliver antibodies, but also to
      serve as a scaffold for neural regeneration following their implantation into
      injured tissue. Since unmodified hyaluronic acid-hydrogels do not support cell
      attachment, the gels were modified with polyclonal anti-Nogo-66 receptor with the
      aim of altering the surface properties of the gels in such a way as to improve
      neuronal adherence and survival. After evaluating the immobilization efficiency
      of the system, chicken dorsal root ganglia and dorsal root ganglia cells were
      planted on the surface of the modified gels to determine cell viability. Dorsal
      root ganglia were also cultured close to the gels in order to assay the
      inducement of neurite outgrowth. In dorsal root ganglia and cell viability assay,
      dorsal root ganglia and neuron cells could adhere to the modified hydrogels and
      survive well, but it did not happen to unmodified hydrogels. After 72 h, these
      attached cells were stained positively with immuno-staining for neurofilament.
      Neurite outgrowth inducement assay showed that the number and length of dorsal
      root ganglia neurites on the side toward modified hydrogels were significantly
      more than that on the opposite side (both P<0.01). The results reveal that
      hyaluronic acid-hydrogels modified with anti-Nogo-66 receptor can support neural
      cell attachment and survival in vitro. Furthermore, this system can greatly
      induce neurite outgrowth. The results also indicate that this modified hydrogels
      have potential to repair injury in the CNS.

PMID- 16298085
TI  - Cell aging in relation to stress arousal and cardiovascular disease risk factors.
AB  - We previously reported that psychological stress is linked to and possibly
      accelerates cellular aging, as reflected by lower PBMC telomerase and shortened
      telomeres. Psychological stress is a major risk factor for cardiovascular disease
      (CVD), with multiple behavioral and physiological mediators. Telomere shortness
      has been associated with CVD, but the relationship between low telomerase
      activity, a potential precursor to telomere shortening, and CVD risk factors has
      not been examined in humans. Here we examine whether telomere length and
      telomerase in leukocytes are associated with physiological signs of stress
      arousal and CVD risk factors in 62 healthy women. Low telomerase activity in
      leukocytes was associated with exaggerated autonomic reactivity to acute mental
      stress and elevated nocturnal epinephrine. Further, low telomerase activity was
      associated with the major risk factors for CVD -smoking, poor lipid profile, high
      systolic blood pressure, high fasting glucose, greater abdominal adiposity-as
      well as to a composite Metabolic Syndrome variable. Telomere length was related
      only to elevated stress hormones (catecholamines and cortisol). Thus, we propose
      that low leukocyte telomerase constitutes an early marker of CVD risk, possibly
      preceding shortened telomeres, that results in part from chronic stress arousal.
      Possible cellular mechanisms by which low telomerase may link stress and
      traditional risk factors to CVD are discussed. These findings may implicate
      telomerase as a novel and important mediator of the effects of psychological
      stress on physical health and disease.

PMID- 16298086
TI  - [Systematic screening tests for Chlamydia trachomatis, Mycoplasma hominis and
      Ureaplasma urealyticum in urogenital specimens of infertile couples].
AB  - We conducted a prospective study on 100 couples consulting for infertility at the
      teaching Hospital of Tours, with the scope to determine if there is a benefit for
      systematic screening of Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma
      urealyticum among genito-urinary specimen when exploring couples infertility. C.
      trachomatis was detected by PCR on sperm, endocervix and urine specimen. M.
      hominis and U. urealyticum were detected by culture on A7 agar medium and with
      minigaleries on sperm and endocervix specimen. Standard cultures were also
      performed on sperm, endocervix, vaginal and urine specimen. Only one specimen
      (sperm) was positive for C. trachomatis. Three percent of the specimen were
      positive for U. urealyticum (from which 2,5% of the sperm specimen). No specimen
      was positive for M. hominis. Our results show that screening of C. trachomatis,
      M. hominis and U. urealyticum is not systematically required for among check up
      of infertile couples, given the prevalence of chlamydiosis among the population
      studied. However, it would be interesting to perform it on a targeted population,
      according to anamnestic or clinical criteria. In addition, an important
      modification of vaginal flora was observed in 12% of cases, and 2 vaginosis were
      diagnosed; the putative consequences of this disequilibrium has to be further
      investigated.

PMID- 16298087
TI  - The acute effects of gabapentin in combination with alcohol in heavy drinkers.
AB  - BACKGROUND: Alcohol effects in humans involve gamma-amino butyric acid (GABA)
      neurotransmission. It has been proposed that GABAergic medications may be
      effective in the treatment of alcohol dependence. This study evaluated the acute
      effects of gabapentin, an anticonvulsant that increases extracellular GABA, on
      the subjective, physiological, and performance effects of alcohol in heavy (mean
      34 drinks per week) alcohol drinkers. METHODS: Seventeen volunteers without
      alcohol dependence were tested using a double-blind design with three 3-day long
      inpatient phases, each separated by at least a 1-week wash-out period. Each
      phase, gabapentin (0, 1000, or 2000mg) was administered 4h before alcohol
      (0.75g/kg), which was given in four divided doses every 20min. RESULTS:
      Gabapentin impaired the ability to balance without producing changes in
      subjective, physiological or other performance measures. Pretreatment with
      gabapentin did not significantly alter subjective and performance effects of
      alcohol and did not alter alcohol craving. Gabapentin, dose-dependently enhanced
      alcohol-induced tachycardia. CONCLUSIONS: Acute gabapentin administration was
      well tolerated in combination with alcohol, but did not alter the effects of
      alcohol.

PMID- 16298088
TI  - The role of the early therapeutic alliance in predicting drug treatment dropout.
AB  - BACKGROUND: To investigate the role of the therapeutic alliance in predicting
      length of retention in residential drug treatment. METHODS: The study recruited
      187 clients starting residential rehabilitation treatment for drug misuse in
      three UK services. Counsellor and client information was assessed at intake, and
      the average total scores of client and counsellor ratings on the WAI-S (obtained
      during weeks 1-3) were use as the alliance measure. Length of retention and
      treatment completion (stay beyond 90 days) were used as measures of retention.
      RESULTS: Clients with weak counsellor rated alliances dropped out of treatment
      significantly sooner than clients with strong counsellor rated therapeutic
      alliances, whether or not the model adjusted for individual counsellor effects
      and potential confounders including psychological well-being, treatment
      motivation and readiness, coping strategies, and attachment style. The client
      rated alliance did not predict length of retention. Apart from the alliance, pre
      treatment crack use, secure attachment style and better coping strategies were
      associated with shorter retention, whereas greater confidence in treatment, older
      client age and better education predicted treatment completion. Counsellors with
      greater experience of delivering drug counselling retained clients longer.
      CONCLUSIONS: The findings of this study stress the importance of treatment
      professionals attending to the therapeutic alliance in drug treatment, as
      counsellors' alliance ratings were found to be amongst the strongest predictors
      of dropout. Using alliance measures as clinical tools may help treatment
      practitioners to become aware of the risk of disengagement early on. Prospective
      studies are needed to evaluate whether strategies of reallocating clients with
      poor alliances to different counsellors lead to improvements in retention.

PMID- 16298089
TI  - Designer zinc-finger proteins and their applications.
AB  - The Cys(2)His(2) zinc finger is one of the most common DNA-binding motifs in
      Eukaryota. A simple mode of DNA recognition by the Cys(2)His(2) zinc finger
      domain provides an ideal scaffold for designing proteins with novel sequence
      specificities. The ability to bind specifically to virtually any DNA sequence
      combined with the potential of fusing them with effector domains has led to the
      technology of engineering of chimeric DNA-modifying enzymes and transcription
      factors. This in turn has opened the possibility of using the engineered zinc
      finger-based factors as novel human therapeutics. One such synthetic factor
      designer zinc finger transcription activator of the vascular endothelial growth
      factor A gene-has recently entered clinical trials to evaluate the ability of
      stimulating the growth of blood vessels in treating the peripheral arterial
      obstructive disease. This review concentrates on the aspects of natural
      Cys(2)His(2) zinc fingers evolution and fundamental steps in design of engineered
      zinc finger proteins. The applications of engineered zinc finger proteins are
      discussed in a context of the mechanism mediating their effect on the targeted
      DNA. Furthermore, the regulation of the expression of zinc finger proteins and
      their targeting to various cellular compartments and to chromatin and non
      chromatin target templates are described. Also possible future applications of
      designer zinc finger proteins are discussed.

PMID- 16298090
TI  - Effect of presence of clinical and subclinical endometritis at the initiation of
      Presynch-Ovsynch program on the first service pregnancy in dairy cows.
AB  - The present study examined the effect of presence of clinical or subclinical
      endometritis at the initiation of Presynch-Ovsynch estrous synchronization
      program on the first service pregnancy rate in dairy cows. Lactating Holstein
      cows (N=275) were given a thorough reproductive examination at 32-38 days in
      milk, 3 days prior to the scheduled start of Presynch-Ovsynch program. Based on
      the reproductive exam findings the cows were diagnosed and classified into three
      groups as clinical endometritis, subclinical endometritis and normal. All cows
      received two set-up injections of 25mg PGF(2alpha) (Lutalyse((R)), Pfizer Animal
      Health, New York, NY, USA) i.m., 14 days apart starting at 35-42 days in milk
      (DIM). All cows received 75microg of GnRH (Cystorelin, Merial, Iselin, NJ, USA)
      i.m. 14 days after the second pre-synchronization injection of PGF(2alpha),
      followed by a third injection of 25mg PGF(2alpha) i.m. 7 days later. Cows
      received a second injection of 75microg of GnRH i.m. 54h after the third
      PGF(2alpha), and received timed artificial insemination at the time of the second
      GnRH injection or 24h later. Multivariate logistic regression was used to analyze
      the odds of pregnancy at the first service. Variables included in the model were
      endometritis status (clinical endometritis, subclinical endometritis and normal),
      farm (two), presence of corpus luteum (CL, yes or no), timing of second GnRH in
      relation to AI (0 or 24h), sire fertility (bulls with greater compared with
      lesser estimated relative conception rates), parity (primiparous and multiparous)
      and their interactions. Of all variable included in the model, cows with corpus
      letuem (OR=1.83 versus OR=1.00; P=0.05) 3 days prior to the scheduled start of
      Presynch-Ovsynch program and primiparous cows (OR=1.00 versus OR=0.55; P=0.04)
      had increased odds of becoming pregnant at the first service. No differences were
      found in the odds of first service pregnancy among clinical, subclinical
      endometritis and normal cows (P>0.1). In summary, presence of clinical or
      subclinical endometritis at the initiation of Presynch-Ovsynch estrous
      synchronization program does not harm the first service pregnancy rate in dairy
      cows.

PMID- 16298091
TI  - Folate-mediated targeting of polymeric conjugates of gemcitabine.
AB  - The synthesis of two new macromolecular prodrugs for active tumor targeting was
      set up. Gemcitabine (2'-deoxy-2',2'-difluorocytidine) was conjugated to
      alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) through succinyl or
      diglycolyl hydrolysable spacers. The targeting agent folic acid was attached to
      the macromolecular backbone through the aminocaproic spacer. The two conjugates
      [PHEA-(5'-succinylgemcitabine)-1'-carboxypentyl-folamide and PHEA-(5'-diglycolyl
      gemcitabine)-1'-carboxypentyl-folamide], were purified and extensively
      characterised by spectroscopic (UV, IR and NMR) and chromatographic analyses to
      determine the correct chemical structure, the purity degree and the reaction
      yield. In vitro studies demonstrated that the drug release depends on the spacer
      arm (diglycolyil or succinyl) and incubation pH. After 30 h incubation at pH 7.4,
      mimicking the plasma and extracellular compartments, the gemcitabine release from
      the succinyl and diglycolyl derivatives was 28 and 31%, respectively. After 30 h
      incubation at pH 5.5, mimicking the lisosomial compartment, the drug released
      from both bioconjugates was lower than 13%. In plasma, the polymer conjugation
      increased the drug stability and provided for a sustained drug release. In vitro
      citotoxicity studies performed using human nasopharyngeal epidermal carcinoma KB
      cells demonstrated that PHEA-(5'-succinylgemcitabine)-1'-carboxypentyl-folamide
      displays an higher dose dependent cytotoxic effect with respect to PHEA-(5'
      diglycolyl-gemcitabine)-1'-carboxypentyl-folamide.

PMID- 16298092
TI  - Probable role of spinal purinoceptors in the analgesic effect of Trigonella
      foenum (TFG) leaves extract.
AB  - In our previous work, we demonstrated that Trigonella foenum (TFG) leaves extract
      can exert analgesic effects in both formalin (F.T.) and tail flick (T.F.) tests.
      Spinal serotonergic system, but not endogenous opioid system, was involved in TFG
      induced analgesia (in the second phase of formalin test). Some reports concern
      the similarity between NSAIDs and TFG extract in many pharmacological effects or
      the interaction between NSAIDs and purinergic system; so the present study was
      designed to investigate the relationship between TFG extract and purinergic
      system or the inhibition of cyclo-oxygenase (COX). We examined the effect of TFG
      extract on: (1) the response of rabbit platelets to ADP induced aggregation, (2)
      the contraction of mouse vas deferens induced by alpha,beta-Me-ATP (a P(2)
      receptor agonist; this receptor mediates the rapid phase of ADP- and ATP-evoked
      influx of Ca(2+) through a non-specific cation channel in platelets), (3)
      alpha,beta-Me-ATP induced hyperalgesia in tail flick test in male rats and (4)
      the specific inhibition of COX-1 and COX-2. Our results showed that TFG extract
      (0.5, 1, 1.5, 3 mg/ml) inhibited ADP (10(-5) mol) induced platelet aggregation
      (IC(50)=1.28 mg/ml). alpha,beta-Me-ATP (30 microM) induced isometric contraction
      in vas deferens while suramin (a P(2) receptor antagonist, 50, 150, 300 microM)
      or TFG extract (0.5, 1, 2, 3 mg/ml) inhibited this effect significantly (IC(50)
      were 91.07 microM and 1.57 mg/ml, respectively). Moreover, alpha,beta-Me-ATP (3
      microg/rat, i.t.) induced hyperalgesia in tail flick test, but it was prevented
      by co-injection of alpha,beta-Me-ATP with suramin (120 microg/rat, i.t.) or TFG
      extract (1mg/rat, i.t.). Effective concentrations of TFG extract in the above
      mentioned experiments did not inhibit COX enzymes in EIA tests. In conclusion,
      these results indicate that the blocking of spinal purinoceptors may contribute
      in the analgesic effect of TFG leaves extract.

PMID- 16298093
TI  - Gastroprotective effect of cardamom, Elettaria cardamomum Maton. fruits in rats.
AB  - Cardamom, the fruits of Elettaria cardamomum Maton. (Zingiberaceae) commonly
      known as "Heel khurd" is used in Unani system of medicine to treat
      gastrointestinal disorders. A crude methanolic extract (TM), essential oil (EO),
      petroleum ether soluble (PS) and insoluble (PI) fractions of methanolic extract,
      were studied in rats at doses of 100-500, 12.5-50, 12.5-150 and 450 mg/kg,
      respectively for their ability to inhibit the gastric lesions induced by aspirin,
      ethanol and pylorous ligature. In addition their effects on wall mucus and
      gastric acid output were recorded. All fractions (TM, EO, PS, PI) significantly
      inhibited gastric lesions induced by ethanol and aspirin but not those induced by
      pylorus ligation. TM proved to be active reducing lesions by about 70% in the
      EtOH-induced ulcer model at 500 mg/kg. The PS fraction reduced the lesions by 50%
      at 50 and 100mg/kg (no dose response was observed) with similar effect than the
      PI fraction at 450 mg/kg. In the aspirin-induced gastric ulcer, the best
      gastroprotective effect was found in the PS fraction, which inhibited lesions by
      nearly 100% at 12.5mg/kg. In our experimental conditions, the PS extract at doses
      >or=12.5mg/kg proved to be more active than ranitidine at 50mg/kg.

PMID- 16298094
TI  - Antidiarrhoeal activity of the ethanol extract of Paederia foetida Linn.
      (Rubiaceae).
AB  - Paederia foetida L. is used as a remedy for diarrhoea and dysentery in Asia, but
      has not been investigated for its antidiarrhoeal properties. Antidiarrhoeal
      activity of 90% ethanol extract of Paederia foetida was investigated in this
      study using castor oil and magnesium sulphate-induced diarrhoea models in mice.
      The extract significantly increased the latent period of diarrhoea in both the
      models. In the castor oil study, the purging index (PI) value lowered in 1 h of
      the study at (100, 250 and 500 mg/kg) doses. The effect continued up to 6-h
      period only at 500 mg/kg dose. The plant notably reduced the purging index value
      in a dose-dependent manner in magnesium sulphate-induced diarrhoea. Paederia
      foetida, in general, reduced the gastrointestinal motility with barium sulphate
      milk both in 15- and 30-min time intervals. The extract significantly decreased
      the cisplatin-induced gastrointestinal motility at all doses at both time
      intervals. The extract also enhanced the morphine-induced reduction of motility
      at 500 mg/kg dose level at both time intervals. The results suggest that Paederia
      foetida showed antidiarrhoeal activity by inhibiting intestinal motility and
      justify its use in traditional medicine.

PMID- 16298095
TI  - Anti-herpes virus activity of Dunbaria bella Prain.
AB  - The herpes inhibitory effect of Dunbaria bella Prain (Fabaceae), a Thai medicinal
      plant traditionally used to treat viral infections was investigated. Using a
      bioassay-guided fractionation procedure, tertiary fractionation of a
      dichloromethane-methanol plant extract afforded a partially purified fraction
      (Fr.372) equally active against replication of herpes simplex virus (HSV) types 1
      and 2. The 50% inhibitory concentration determined by a viral yield-inhibition
      assay was 1.21-1.25 microg/ml and the antiviral selectivity was about 17-fold.
      Treatment of HSV with high concentrations of Fr.372 followed by removal before
      infection had little effect on subsequent viral yield indicating the active
      principle(s) were not inactivating the virus. Concentrations greater than 0.5
      microg/ml significantly inhibited viral release more than cell-associated virus
      suggesting that one or more active ingredients may inhibit viral release.
      Furthermore, the antiviral activity was dependent on multiplicity of infection
      and the type of host cell. Preliminary chemical analysis showed that Fr.372
      contained neither phenolic compounds nor alkaloids.

PMID- 16298096
TI  - Toxicological evaluation of an ethanolic extract from Chiococca alba roots.
AB  - The roots of Chiococca alba have been employed to treat rheumatic disorders and
      for other therapeutic purposes in Brazil and elsewhere. This study was undertaken
      to evaluate the toxicological properties of an ethanolic extract from Chiococca
      alba roots (EE), including mutagenicity in the Salmonella assay and acute and
      subacute toxicity to mice. Single oral doses of EE caused hypoactivity, but no
      deaths were noted up to the highest dose tested (2000 mg/kg). EE (500 mg/kg p.o.)
      reduced mouse locomotion in the open field test. EE was markedly more toxic when
      given by intraperitoneal (i.p.) and subcutaneous (s.c.) routes. Acute approximate
      lethal doses (ALD) were 125 mg/kg (males) and 250 mg/kg (females) and 250 mg/kg
      (both sexes) by i.p. and s.c. routes, respectively. Deaths after single doses
      were preceded by hypoactivity, ataxia and lethargy. Repeated administration of EE
      by gavage for 14 days caused no deaths. Activity of liver monooxygenases (pentoxy
      and ethoxyresorufin-O-dealkylases) was not altered by repeated treatment with EE
      (2000 mg/kg/day p.o.). Administration of EE by the i.p. route for 14 days
      decreased weight gain and caused anemia, neutrophilia and deaths. The no-observed
      adverse-effect level (NOAEL) for subacute treatment by the i.p. route was as low
      as 15.6 mg of EE/kg body weight (wt)/day. EE was not mutagenic in the
      Salmonella/microsome assay with TA100, TA98, TA97a and TA1535 strains. In
      summary, EE was not mutagenic and presented a low acute and subacute toxicity by
      the oral route. Toxicities by parenteral routes, however, were more pronounced.

PMID- 16298097
TI  - Allele distribution of 15 STR loci used for human identity purposes in the Greek
      Cypriot population of the island of Cyprus.
AB  - Allele frequencies for 15 STRs (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51,
      D5S818, D13S317, D7S820, THO1, Penta E, D16S539, CSF1PO, Penta D and TPOX) in the
      PowerPlex-16 System (Promega Corporation) were derived from a sample of 1475
      unrelated Greek Cypriot individuals from the island of Cyprus.

PMID- 16298098
TI  - Discrepancies between forensic identification kits explained by a laser power
      supply shutdown.
AB  - The occurrence of two null alleles for the same individual was suspected because
      of the discrepancy at two loci (vWA and THO1) between genotypes characterized by
      the mean of two different commercial kits. Reanalysis of the samples indicated
      there was no null allele, and that this abnormality was indeed related to an
      automatic laser power shutdown. The laser power supply was set to a value (6.4V)
      too close to the automatic shutdown threshold (6.0V). The alleles were undetected
      because of the absence of emission at the time of migration of the two alleles
      through the detection device. However, since no alarm is triggered in such an
      event, the users should monitor their laser power supply values.

PMID- 16298099
TI  - Determination of methenamine, methenamine mandelate and methenamine hippurate in
      pharmaceutical preparations using ion-exchange HPLC.
AB  - An ion-exchange column high-performance liquid chromatography (HPLC) method has
      been developed for the determination of methenamine in methenamine and
      methenamine hippurate pharmaceutical preparations. The HPLC method uses a Zorbax
      SCX-300 column with acetonitrile-0.1M sodium perchlorate monohydrate (pH 5.8)
      (70:30, v/v) as the mobile phase at the flow rate of 1 mL/min. UV-detection was
      at 212 nm. The linear concentration plots for methenamine were linear over the
      concentration range of 0.25-50mM for methenamine and methenamine mandelate
      standards. The intra-day RSD precision was <1.25%, and for inter-day, <1.85%. The
      peaks for mandelic acid, hippuric acid and the other ingredients from placebo
      tablets do not interfere with the analysis for methenamine. The accuracy of this
      method was shown to be 99-101% by measuring the recovery of methenamine from
      spiked placebo tablets. The assay of methenamine from methenamine hippurate
      tablets and from a urinary antiseptic tablet containing methenamine were in the
      range of 98-102%. This HPLC method is a fast, simple and straightforward method
      for the analysis of methenamine in pharmaceutical preparations.

PMID- 16298101
TI  - [Septic shock: blood glucose regulation].
AB  - Blood glucose regulation is controlled by several hormones, neurological
      mechanisms and the hepatic autoregulation. Glucose uptake necessitates glucose
      transporters which are called GLUT. In physiological situation, 80% of glucose
      uptake of the whole body is produced by the non-insulin dependant tissues, via
      the GLUT 1 to 3 transporters. Glucose uptake by insulin dependant tissues is
      mediated by insuline, which activates GLUT-4 transporters. Because of the
      production of pro-inflammatory mediators (TNF-alpha), sepsis induces
      hyperglycemia, which results essentially from an hepatic insulinoresistance. This
      phenomenon leads to an acute load and uptake of glucose by the non-insulin
      dependant tissues. Hyperglycemia modifies inflammatory and immune reactions and
      enhances the production of reactive oxygen species. Thus, sepsis has an impact on
      blood glucose control and conversely. Blood glucose control has been found to
      decrease mortality and morbidity in critically ill patients. The exact mechanism,
      by which these beneficial effects are produced, remains controversial, due to
      euglycemia or to insulin infusion. Probably both mechanisms are implicated. In
      all cases the beneficial effects seem to be multifactorial: a decrease in
      oxydative stress, a protective effect in front of the burst suppression, multiple
      anti-inflammatory effects. The optimum level of blood glucose is still discussed
      and must be evaluated in further studies. In all cases, blood glucose level must
      be under or equal to 1,4 g/l. Even no clinical study evaluates precisely the
      impact of hyperglycemia during sepsis, a lot of arguments supports that blood
      glucose level must be a therapeutic goal in these situations.

PMID- 16298100
TI  - Total antioxidant capacity is impaired in different structures from aged rat
      brain.
AB  - Our data support a disproportion between free radicals levels and scavenging
      systems activity in different cerebral regions of the aging rat. We investigated
      the total reactive antioxidant potential and reactivity levels, which represent
      the total antioxidant capacity, in different cerebral regions of the aging rat
      (cortex, striatum, hippocampus and the cerebellum). In addition, we have
      determined several oxidative stress parameters, specifically the free radicals
      levels, the macromolecules damage (lipid peroxidation and carbonyl content), as
      well as the antioxidant enzymes activities in different cerebral areas from young
      (2 months-old), mature adult (6 months-old) and old (24 months-old) male Wistar
      rats. Free radicals levels, determined by 2',7'-dichlorofluorescein diacetate
      probe, were higher in striatum, cerebellum and hippocampus from aged rats. There
      was an age-related increase in lipoperoxidation in hippocampus and cerebral
      cortex. In the cerebellum, a high activity of superoxide dismutase and a decrease
      of catalase activity were observed. The striatum exhibited a significant catalase
      activity decrease; and glutathione peroxidase activity was diminished in the
      hippocampus of mature and aged rats. There was a marked decrease of total
      antioxidant capacity in hippocampus in both reactivity and potential levels,
      whereas striatum and cerebral cortex displayed a reduction on reactivity assay.
      We suggest that age-related variations of total antioxidant defenses in brain may
      predispose structures to oxidative stress-related neurodegenerative disorders.

PMID- 16298102
TI  - Dunkerque City air pollution particulate matter-induced cytotoxicity, oxidative
      stress and inflammation in human epithelial lung cells (L132) in culture.
AB  - Exposure to urban airborne particulate matter (PM) has been associated with
      adverse health effects. In this work, we focused our attention on the capacity of
      air pollution PM to induce cytotoxic, oxidative stress, and inflammatory
      responses in human epithelial lung cells (L132) in culture. PM were collected in
      Dunkerque, a French seaside city, and their physical and chemical characteristics
      were carried out. Their size distribution showed that 92.15% of the PM were equal
      or smaller than 2.5 and their specific surface area was 1 m2/g. Inorganic (i.e.
      Fe, Al, Ca, Na, K, Mg, Pb, etc.) and organic (i.e. VOC, PAH, etc.) chemicals were
      found in PM. Physical and chemical properties of Dunkerque City's PM suggested
      that much of the collected PM derived from wind-borne dust from the industrial
      complex and the heavy motor vehicle traffic. Their cytotoxicity, as evaluated by
      survival rate determination, lactate dehydrogenase activity, and mitochondrial
      dehydrogenase activity showed concentration and time-dependent effects in L132
      cells (LC10 = 18.84 microg PM/ml; LC50 = 75.36 microg PM/ml). Moreover, in PM
      exposed L132 cells, there were concentration- and time-dependent changes in lipid
      peroxidation, superoxide dismutase activity, 8-hydroxy-2'-deoxyguanosine
      formation, and poly(ADP-ribosyl)ation, on the one hand, and in tumor necrosis
      factor-alpha secretion, inducible nitric oxide synthase activity, and nitric
      oxide release, on the other hand. Taken together, these findings suggested that
      oxidative stress and inflammatory responses proceeded cytotoxicity in PM-exposed
      L132 cells.

PMID- 16298103
TI  - An evaluation of strategies to maintain mands at practical levels.
AB  - In order to teach individuals with developmental disabilities to request stimuli
      they are motivated to obtain (mand), it is often necessary to initially deliver
      the item requested immediately and frequently. This may result in an undesirably
      high rate of mands that is impractical to maintain. The purpose of the current
      investigation was to extend the findings of previous research on the maintenance
      of low-rate mands within a communication-training context for children diagnosed
      with autism by evaluating the efficacy of two procedures: (1) signaled delay-to
      reinforcement and (2) multiple schedules. The results of our evaluation of
      multiple schedules replicated those of previous research; this arrangement was
      found for all participants to be effective in maintaining mands at low rates
      under multiple schedules with a 270-s extinction component and 30-s reinforcement
      component. For all participants, signaled delay-to-reinforcement was ineffective
      in maintaining mands at the terminal criterion, a 270-s delay.

PMID- 16298104
TI  - G-protein alpha subunit interaction and guanine nucleotide dissociation inhibitor
      activity of the dual GoLoco motif protein PCP-2 (Purkinje cell protein-2).
AB  - Purkinje cell protein-2 (PCP-2; L7/GPSM4) is a GoLoco motif-containing protein
      that is specifically expressed in Purkinje and retinal ON bipolar cells. An
      alternative splice variant of PCP-2 has recently been isolated which contains two
      GoLoco motifs. Although the second GoLoco motif (GL2) of PCP-2 has been reported
      to interact with Galpha-subunits, a complete biochemical analysis of each
      individual motif of PCP-2 has not been performed. We demonstrate that the first
      GoLoco motif (GL1) of PCP-2 is equipotent as a guanine nucleotide dissociation
      inhibitor (GDI) towards Galphai1 and Galphai2, while it has sevenfold lower GDI
      activity for Galphai3 and greater than 20-fold lower GDI activity against
      Galphao. In contrast we found PCP-2 GL2 to be essentially equipotent as a GDI for
      all Galphai subunits, but it had negligible activity toward Galphao. Using co
      immunoprecipitation from COS-7 cells, we found that PCP-2 was only able to
      interact with Galphai1 but not Galphao nor Galpha-subunits from other families
      (Galphas, Galphaq, or Galpha12). Mutational analysis of a non-canonical residue
      (glycine 24) in human PCP-2 GL1 provided evidence for heterogeneity in mechanisms
      of Galphai interactions with GoLoco motifs. Collectively, the data demonstrate
      that PCP-2 is a comparatively weak GoLoco motif protein that exhibits highest
      affinity interactions and GDI activity toward Galphai1, Galphai2, and Galphai3
      subunits.

PMID- 16298105
TI  - Schizotypy is increased in mixed-handers, especially right-handed writers who use
      the left hand for primary actions.
AB  - Associations between schizotypy and handedness were examined in 733
      undergraduates for the Sta and Unex scales of the O-LIFE inventory and several
      measures derived from the Annett hand preference questionnaire. Higher schizotypy
      scores were found for mixed-handers defined in various ways, including
      inconsistent preference for any item of the questionnaire and also the presence
      of either hand responses. There was a marked elevation of schizotypy scores
      (p<.001) for right-handed writers who prefer the left hand for other 'primary'
      actions (throwing, racket, match, hammer, toothbrush and scissors). This
      observation was replicated in 182 students assessed on the Rust Scale of
      Schizotypal Cognitions. Several findings agree that inconsistent hand preference
      is associated with a raised probability of schizotypal thinking.

PMID- 16298106
TI  - An empirical evaluation of the Arizona sexual experience scale and a simple one
      item screening test for assessing antipsychotic-related sexual dysfunction in
      outpatients with schizophrenia and schizoaffective disorder.
AB  - We examined the reliability and construct validity of the 5-Item Arizona Sexual
      Experience Scale (ASEX) in patients with schizophrenia or schizoaffective
      disorder. In addition, we assessed the performance of two 1-item screening
      questions to detect sexual dysfunction as defined by a cut-off scoring criteria
      of sexual dysfunction for the ASEX. One question was a general question about any
      side effects. The second question asked specifically about sexual dysfunction.
      Altogether 247 participants with a DSM-IV diagnosis of schizophrenia or
      schizoaffective disorder provided data at a single interview. Results indicated
      that the ASEX has good internal consistency and construct validity for the
      patients with schizophrenia and schizoaffective disorder. The point-biserial
      correlations and logistic regression found a high degree of agreement between the
      one-item specific screening question for sexual dysfunction and the ASEX.
      Overall, sensitivity (85%), specificity (63.7%), and positive (83%) and negative
      (67.1%) predictive values for the specific one-item screening question were
      satisfactory. The single general side effect question performed poorly
      (sensitivity=11.3%; specificity=92.5%; positive predictive value=76%; negative
      predictive value=33%). The current findings demonstrate the highly acceptable
      psychometric properties of the ASEX in patients with schizophrenia or
      schizoaffective disorder. In addition, a specific one-item screening question is
      of clinical utility in patients with schizophrenia or schizoaffective disorder.

PMID- 16298107
TI  - Course of substance misuse and daily tobacco use in first-episode psychosis.
AB  - BACKGROUND: Study of the course of substance misuse and daily tobacco use in
      first-episode psychosis may enhance detection and treatment of these substance
      related problems. METHODS: This 15-month follow-up study examined the course of
      substance misuse and daily tobacco use in 103 individuals treated for first
      episode psychosis. RESULTS: Three-quarters (72.6%) of patients with lifetime
      substance misuse, or half (51.5%) of all patients, continued substance misuse
      (primarily cannabis) during the 15-month follow-up period. There was a
      significant reduction in the rate of any substance misuse (70.9% versus 53.4%)
      but not daily tobacco use (76.7% versus 75.7%) between baseline and 15-month
      follow-up. Patients who continued substance misuse showed a significant reduction
      in the severity and frequency of substance use between baseline and follow-up.
      Patients who continued substance misuse were more likely to be younger, male and
      single, less likely to have completed secondary school, and more likely to have
      had more severe cannabis use prior to entry to treatment compared to patients who
      ceased substance misuse. DISCUSSION: A significant proportion of young patients
      treated for first-episode psychosis are at risk of mental and physical health
      problems associated with substance misuse and/or regular tobacco use.

PMID- 16298108
TI  - Comment on "N-acetylaspartate reductions in the mediodorsal and anterior thalamus
      in men with schizophrenia verified by tissue volume corrected proton MRSI"
      (Schizophr Res 76, 173-185, 2005).

PMID- 16298109
TI  - Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non
      geriatric outpatients with major depressive disorder (Part I).
AB  - The objective of the present work was to study the interrelationship between
      white matter hyperintensities (WMHs), cardiovascular risk factors and elements of
      the one-carbon cycle including serum folate, vitamin B12, and homocysteine levels
      in a relatively young sample of outpatients with major depressive disorder (MDD),
      and to compare the severity of white matter hyperintensities in MDD patients and
      healthy volunteers. Fifty MDD outpatients (34% women, age 40.6+/-10.3 years),
      free of psychotropic medications for at least 2 weeks before enrollment,
      underwent magnetic resonance imaging (MRI) scans of the brain to detect T2 WMHs
      and also had (1) serum folate, vitamin B12, homocysteine and cholesterol levels
      measured, and (2) cardiovascular risk factors assessed during the same study
      visit. Thirty-five healthy comparison subjects (40% women, age 39.2+/-9.8 years)
      also underwent brain MRI scans. Hypofolatemia, hypertension and age independently
      predicted a greater severity of total brain WMHs. Separately, the same factors
      also predicted a greater severity of subcortical WMHs. Hypofolatemic and
      hypertensive patients had more severe WMHs than normal controls. In light of the
      adverse impact of WMHs on a number of health-related outcomes later in life,
      hypofolatemia and hypertension may represent modifiable risk factors to prevent
      the occurrence of such adverse outcomes.

PMID- 16298111
TI  - On the relationship between interoceptive awareness, emotional experience, and
      brain processes.
AB  - The perception of visceral signals plays a crucial role in many theories of
      emotions. The present study was designed to investigate the relationship between
      interoceptive awareness and emotion-related brain activity. 44 participants (16
      male, 28 female) first underwent a heartbeat perception task and then were
      categorised either as good (n = 22) or poor heartbeat perceivers (n = 22). A
      total of 60 different pictures (pleasant, unpleasant, neutral) from the
      International Affective Picture System served as emotional stimuli. EEG (61
      electrodes) and EOG were recorded during slide presentation. After each slide,
      the subjects had to rate emotional valence and arousal on a 9-point self-report
      scale. Good heartbeat perceivers scored the emotional slides significantly more
      arousing than poor heartbeat perceivers; no differences were found in the
      emotional valence ratings. The visually evoked potentials of good and poor
      heartbeat perceivers showed significant differences in the P300 and in the slow
      wave latency ranges. Statistical analyses revealed significantly higher P300 mean
      amplitudes for good heartbeat perceivers (averaged across all 60 slides) than for
      poor heartbeat perceivers. In the slow-wave range, this effect was found for
      affective slides only. Heartbeat perception scores correlated significantly and
      positively with both the mean arousal rating as well as with the mean amplitudes
      in the P300 time window and the slow-wave window. Our results demonstrate a
      strong relationship between the perception of cardiac signals and the cortical
      processing of emotional stimuli, as would be postulated for example by the James
      Lange theory of emotions.

PMID- 16298110
TI  - Modeling of 31P-NMR spectra of magnetically oriented phospholipid liposomes: A
      new analytical solution.
AB  - 31P-NMR spectroscopy is widely used for studies of phospholipid liposomes, a
      commonly used model of a biological membrane. For the correct analysis of 31P-NMR
      spectra of the liposomes it is necessary to take into account that they are
      deformed by the magnetic field of the spectrometer. The liposomes become
      ellipsoidal and this affects the lineshape of the spectrum. In the present
      communication we suggest a new analytical formula for modeling of 31P-NMR spectra
      of the prolate phospholipid liposomes. The formula assumes a Lorentzian
      broadening function and exactly ellipsoidal shape of the liposomes. Based on the
      formula a program called P-FIT is designed for the practical analysis of the
      experimental multicomponent spectra of the prolate liposomes. The versatility of
      the program developed in a Mathematica environment is demonstrated by simulations
      of a number of 31P-NMR spectra with different complexity.

PMID- 16298112
TI  - Specific activation of the V5 brain area by auditory motion processing: an fMRI
      study.
AB  - Previous neuroimaging studies devoted to auditory motion processing have shown
      the involvement of a cerebral network encompassing the temporoparietal and
      premotor areas. Most of these studies were based on a comparison between moving
      stimuli and static stimuli placed at a single location. However, moving stimuli
      vary in spatial location, and therefore motion detection can include both spatial
      localisation and motion processing. In this study, we used fMRI to compare neural
      processing of moving sounds and static sounds in various spatial locations in
      blindfolded sighted subjects. The task consisted of simultaneously determining
      both the nature of a sound stimulus (pure tone or complex sound) and the presence
      or absence of its movement. When movement was present, subjects had to identify
      its direction. This comparison of how moving and static stimuli are processed
      showed the involvement of the parietal lobules, the dorsal and ventral premotor
      cortex and the planum temporale during auditory motion processing. It also showed
      the specific recruitment of V5, the visual motion area. These results suggest
      that the previously proposed network of auditory motion processing is distinct
      from the network of auditory localisation. In addition, they suggest that the
      occipital cortex can process non-visual stimuli and that V5 is not restricted to
      visual processing.

PMID- 16298113
TI  - Structural investigations on lipid nanoparticles containing high amounts of
      lecithin.
AB  - Solid lipid nanoparticles (SLN), an alternative colloidal drug delivery system to
      polymer nanoparticles, emulsions and liposomes, possess inherent low
      incorporation rates resulting from the crystalline structure of the solid lipid.
      To increase the drug loading capacity of SLN, matrix modification by
      incorporation of the amphiphilic lipid lecithin within the lipid matrices has
      been proposed as a promising alternative. The objective of this work is to
      investigate the effects of the lecithin on the microstructure of matrix modified
      SLN. In addition, these systems were checked for the existence of aggregates like
      mixed micelles, liposomes, etc., which could possibly be formed by lecithin
      leakage into the aqueous phase during the preparation process. For this purpose,
      laser diffraction, photon correlation spectroscopy (PCS), small angle X-ray
      scattering (SAXS), nuclear magnetic resonance (NMR) and transmission electron
      microscopy (TEM) were performed to investigate the structure, mobility, and
      molecular environment of the compounds. Lecithin incorporation within the lipid
      matrices resulted in a concentration dependent decrease in particle size up to a
      critical concentration of 30%. Lecithin incorporation up to 50% was investigated
      but caused no further particle size decrease. TEM revealed anisometrical and
      crystalline platelets of ellipsoidal to disc-like shape. Furthermore, SAXS and
      TEM showed no signs of lecithin and nonionic emulsifier derived aggregates in the
      aqueous phase. This points in agreement with NMR measurements to a strong
      attachment of both substances to the SLN surfaces. The proposed structure of the
      particles after melt emulsification consists of two different layers: a
      crystalline triglyceride-rich core is covered in dependence of the lecithin
      content either by a monomolecular or multimolecular lecithin/Solutol HS15 (SOL)
      layer.

PMID- 16298115
TI  - [Mosquito bites allergy, which prevention?].
AB  - Mosquito bites may induce allergic reactions in children. Usually underestimated,
      these reactions are often cutaneous and difficult to distinguish from non
      specific histaminic phenomena. Recently, the identification of major allergens in
      mosquito saliva has allowed the achievement of recombinant allergens, which
      should facilitate the diagnosis and treatment of allergic reactions. Preventive
      cares must be performed in all children with large reactions, allergic or even
      non-allergic. Prevention consists in cutaneous protection, the use of repellents
      (with special attention to their toxicity), and antihistamines. A practical sheet
      for patient is provided.

PMID- 16298116
TI  - [Antenatal closure of ductus arteriosus following maternal intoxication by
      niflumic acid].
AB  - Antenatal closure of the ductus arteriosus is an uncommon event that has been
      considered as a risk factor for development of congestive heart failure and
      persistent pulmonary hypertension of the newborn. We report here on a case of
      antenatal ductus arteriosus closure due to niflumic acid maternal intoxication at
      32 weeks of gestation. Fetal extraction was performed few days later because of
      echographic signs of congestive heart failure. The child survived after 3 days of
      severe persistent pulmonary hypertension. This case emphasizes the potential risk
      of niflumic acid during pregnancy and the need of antenatal echographic
      monitoring for optimal management.

PMID- 16298117
TI  - [Preventing post lumbar puncture complaints by using thin needles (25-G)].

PMID- 16298118
TI  - [Three-dimensional echocardiography in congenital heart disease].
AB  - The introduction of real time three-dimensional (3D) echocardiography has led to
      its use in everyday clinical practice. The 3D matrix probe enables the
      instantaneous acquisition of transthoracic volumes. Several modes of 3D are
      available: 3D volume, biplan and 3D color Doppler. Real time 3D echocardiography
      gave more accurate description of various congenital heart diseases as well as
      valvulopathy, shunt and aorta pathology. Fetal 3D echocardiography is available.
      Quantitative measurement of ventricular volumes could be obtain by 3D
      echocardiography. The facility of utilisation of the matrix probe should lead to
      routine usage of 3D echocardiography as with 2D and Doppler method. Its values
      should be decisive in many congenital cardiac lesions requiring surgery or
      interventional catheterisation.

PMID- 16298119
TI  - [Shaken baby syndrome: investigation beside mothers of newborns].

PMID- 16298120
TI  - [Antimitochondrial agents: a new class of anticancer agents].
AB  - Over the last 2 decades, the role of apoptosis in anticancer agent cytotoxicity
      has become clear. Defects in the regulation of apoptosis (programmed cell death)
      make important contributions to the pathogenesis and progression of most cancers
      and leukemias. Apoptosis defects also have a key role in cell resistance to
      chemotherapy. Mitochondria play a central part in cell death in response to
      anticancer agents. Most of these agents target mitochondria via caspases or other
      regulator elements of the apoptotic machinery. Nevertheless, some anticancer
      agents, already in clinical use (paclitaxel, vinblastine, lonidamine, etoposide,
      arsenic trioxide) or in pre-clinical development (betulinic acid, MT21), directly
      target and permeabilize mitochondria. The acknowledgement of mitochondria as a
      new target for anticancer agents provides a new way to bypass cancer cell
      chemoresistance.

PMID- 16298121
TI  - Heavy metal removal from contaminated sludge for land application: a review.
AB  - In recent years, various methods for heavy metal removal from sewage sludge have
      been extensively studied in order to minimize the prospective health risks of
      sludge during land application. In this paper, a comparative review and critical
      analysis of the application of chemical extraction, bioleaching,
      electroreclamation, and supercritical fluid extraction (SFE), in removing heavy
      metals from contaminated sludges is presented. Moreover, speciation studies,
      which can indicate ease of leachability of the different forms of heavy metals in
      sludge, are also presented. Experimental studies revealed a broad range in metal
      extraction efficiencies of the different extraction technologies. Acid treatment
      seemed to effectively remove Cd, attaining as much as 100% removal for some
      studies, as compared to bioleaching. SFE also gave higher removal efficiency than
      bioleaching. Cr, Pb and Ni seemed to be also effectively removed by the acid
      treatment. For the removal of Cu, Mn and Zn, the bioleaching process seemed to be
      appropriate with maximum removal efficiencies of 91%, 93% and 96% for the three
      metals, respectively, and as high as 64% minimum removal efficiency for Zn. The
      SFE process also gave good results for Cu, Mn and Zn removal. Electroreclamation
      exhibited better removal efficiency for Mn, but is still inferior to acid
      treatment and bioleaching processes. For chemical extraction, because of the
      adverse impacts that can result from the use of inorganic acids and complexing
      agents, interest can be directed more toward utilizing organic acids as
      extracting agents because of their biodegradability and capability to remove
      metals at mildly acidic condition, hence requiring less acid. The bioleaching
      process, although it seems to give a higher yield of metal extraction with lower
      chemical cost than chemical extraction, may be limited by the inability of the
      system to cope with the natural environmental conditions, requires strict
      monitoring of aeration rate and temperature and has applicability to only low
      sludge solids concentration. A full-scale study would be useful to better assess
      the efficiency of the process. The electroreclamation technology is limited by
      its relatively higher energy consumption and limited applicability to sludge. The
      SFE method, on the other hand, is limited by the complexity of the process and
      the cost of ligands suitable for effective metal extraction. Both of these
      technologies are still in their early stage of application and hence there is a
      need for further basic and applied studies. Finally, the common advantage for
      almost all treatment technologies studied is that the extraction efficiencies for
      some metals are high enough to remove metals from sludge to levels suitable for
      land application.

PMID- 16298122
TI  - Municipal solid waste management in the Southern Province of Sri Lanka: problems,
      issues and challenges.
AB  - This paper describes the problems, issues and challenges faced by Sri Lanka based
      on the outcome of a recent study conducted in the country's Southern Province.
      The study consists of a public survey, discussions with local authority staff
      involved in waste management, discussions with Provincial Council and Government
      officials, dialogue with local politicians, review of documents and field
      observations. The study revealed that only 24% of the households have access to
      waste collection and that in rural areas it was less than 2%. A substantial
      number of households in areas without waste collection expect local authorities
      to collect their waste. The study also showed that most sites in the province are
      under capacity to handle any increased demand. Urgent and immediate improvement
      of the waste disposal sites is necessary to meet the current demand for improved
      waste collection. The study also revealed that there is a high willingness of
      people for home composting.

PMID- 16298123
TI  - Fabrication and optimal design of differential electromagnetic transducer for
      implantable middle ear hearing device.
AB  - A differential electromagnetic transducer (DET), with similar frequency
      characteristics to those of a normal middle ear, is designed and implemented for
      use in an implantable middle ear hearing device (IMEHD). To optimize the
      characteristics of the DET that depend on the electromagnetically forced
      vibration, a theoretical analysis is conducted to design the vibrating part. The
      electromagnetic force of the DET is simulated according to the design parameters
      of the coil size using a finite element analysis (FEA). As a result, the maximal
      vibration force is achieved when the optimal length and thickness of the
      cylindrical coil is 70% of the length of the magnets and 56% of their radius. The
      vibration characteristics of the DET are then simulated when applying the maximal
      force. The optimally designed DET is implemented using MEMS technology and
      vibration experiments carried out with the fabricated DET in an unloaded state.
      The vibrating displacement of the DET is about 200 nm within a range between 0.1
      and 1.5 kHz when a current of 1 mA(rms) is applied to the coil. To investigate
      the usefulness of the DET, in vitro and in vivo experiments are conducted using
      the ossicular chain of a cadaver and guinea pig, and the results verify that the
      implemented DET performs well as a transducer for an IMEHD.

PMID- 16298124
TI  - Expression of endothelin-1 is related to poor prognosis in non-small cell lung
      carcinoma.
AB  - The endothelin (ET) system influences tumourigenesis and tumour progression by
      various mechanisms, including angiogenesis. The aim of this study was to
      determine whether the expression of endothelin-1 (ET-1) is related to the
      angiogenic phenomenon in lung cancer and whether it could be involved in its
      clinical behaviour. Expression of ET-1, endothelin-converting enzyme-1 (ECE-1)
      and endothelin-receptors ETA and ETB was examined in 201 non-small cell lung
      carcinoma (NSCLC) and corresponding normal tissues using real-time polymerase
      chain reaction (RT-PCR). Forty NSCLC were also analysed for vascular endothelial
      growth factor (VEGF) expression by a competitive-PCR approach to assess whether
      ET-1 expression was related to this angiogenic factor. A higher number of cases
      with ET-1, ECE-1 and ETA mRNA expression was observed in malignant lung tumours
      compared with normal lung tissues (45.7% versus 33% for ET-1 (P < 0.0001); 38.3%
      versus 16.5% for ECE-1 (P = 0.004); and 42.8% versus 28.5% for ETA (P < 0.0001)).
      On the other hand, ETB mRNA was higher in normal lung tissues than in tumour
      samples (58.5% versus 52.8% (P < 0.0001)). Immunohistochemical analysis was also
      performed in 78 cases, selected from among those with high ET-1 mRNA, to confirm
      the presence of ET-1 protein and to determine its distribution and localisation.
      Moreover, an interesting relationship was observed between ET-1 and VEGF mRNA
      levels (P = 0.02). At univariate analysis, clinical-pathological parameters, such
      as sex, nodal metastatic involvement and stage, and ET-1 expression were seen to
      be significant predictors of worse prognosis regarding both overall survival (P =
      0.001, P = 0.0003, P = 0.001 and P = 0.03, respectively) and disease-free
      interval (P = 0.0005, P = 0.0007, P = 0.001 and P = 0.04, respectively). We
      conclude that ET-1 could be involved in angiogenic phenomena in NSCLC and may
      represent a further indicator of progression and poor prognosis in this type of
      cancer, with interesting therapeutic implications.

PMID- 16298125
TI  - Adjuvant and neoadjuvant chemotherapy for osteosarcoma of the extremities: 27
      year experience at Rizzoli Institute, Italy.
AB  - Around 1148 patients with non-metastatic osteosarcoma of the extremity were
      treated in a single institution between 1972 and 1999 with 4 different protocol
      of adjuvant and 7 different protocols of neoadjuvant chemotherapy. The rate of
      limb salvage increased from 20% to 71%. The 5-year event-free survival (EFS) and
      overall survival (OS) were 57% and 66%, respectively. The 10-year EFS and OS were
      52% and 57%, respectively, and the results significantly correlated with serum
      alkaline phosphatase levels; the type of chemotherapy (adjuvant vs neoadjuvant);
      and with histologic response to pre-operative treatment. Aggressive chemotherapy
      and surgery could cure about the 60% of patients with osteosarcoma of the
      extremity. However, since local or systemic relapses, myocardiopathies and a
      second malignancy are possible even 5 or more years since the beginning of
      treatment, a long-term follow-up is recommended.

PMID- 16298126
TI  - Physical and thermochemical characterization of rice husk char as a potential
      biomass energy source.
AB  - The fixed bed pyrolysis of rice husk was studied under conventional conditions
      with the aim of determining the characteristics of the charcoal formed for its
      applicability as a solid fuel. Thermoanalytic methods were used to determine the
      kinetic parameters of its combustion. Palletisation using different binders and
      techniques to improve the time of sustained combustion of the char pallets were
      investigated. The optimum temperature for carbonization to obtain a char having
      moderately high heating value was found as 400 degrees C. For the active char
      combustion zone, the order of reaction was nearly 1, the activation energy 73.403
      kJ/mol and the pre-exponential factor 4.97 x 10(4)min(-1). Addition of starch as
      a binder and 10% ferrous sulphate heptahydrate or sodium hypophosphite as an
      additive enhanced the ignitibility of the char pallets.

PMID- 16298127
TI  - Convergent, parallel synthesis of a series of beta-substituted 1,2,4-oxadiazole
      butanoic acids as potent and selective alpha(v)beta3 receptor antagonists.
AB  - We describe a series of 1,2,4-oxadiazoles, which are potent antagonists of the
      integrin alpha(v)beta3 and, in addition, show selectivity relative to the other
      beta3 integrin alpha(IIb)beta3. In whole cells, the majority of these analogs
      also demonstrated modest selectivity against other alpha(v) integrins such as
      alpha(v)beta1 and alpha(v)beta6.

PMID- 16298128
TI  - Enhanced FTase activity achieved via piperazine interaction with catalytic zinc.
AB  - Benzocycloheptapyridine tricyclic compounds with piperazine or substituted
      piperidine moieties extending either from the 5- or 6-position of the tricyclic
      bridgehead exhibited enhanced FTase activity: this resulted from favorable
      binding of the ligand nitrogen with the catalytic zinc found in the FTase. A
      single isomer at C-11 with piperazine adduct extending from the 6-position,
      compound 24, exhibited excellent FTase activity with IC50 = 0.007 microM, soft
      agar IC50 = 72 nM, and Rat AUC(PO, 10 mpk) = 4.0 microM x h. X-ray of (-)-[8
      chloro-6-(1-piperazinyl)-1H-benzo[5,6]]cyclohepta[1,2-b]pyridine-11-yl]-1
      (methylsulfonyl)piperidine 24 bound to Ftase revealed favorable interaction
      between piperazine nitrogen and catalytic zinc atom.

PMID- 16298129
TI  - Novel non-nucleobase inhibitors of Staphylococcus aureus DNA polymerase IIIC.
AB  - The preparation and biological evaluation of 5-substituted-6-hydroxy-2
      (anilino)pyrimidinones as a new class of DNA polymerase IIIC inhibitors, required
      for the replication of chromosomal DNA in Gram-positive bacteria, are described.
      These new dGTP competitive inhibitors displayed good levels of in vitro
      inhibition and antibacterial activity against Staphylococcus aureus. A new class
      of dATP competitive inhibitors, 6-substituted-2-amino-5-alkyl-pyrimidin-4-ones,
      whose antibacterial activity was unaffected by serum, were identified.

PMID- 16298130
TI  - Advances toward new antidepressants beyond SSRIs: 1-aryloxy-3-piperidinylpropan-2
      ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 5.
AB  - A series of 1-aryloxy-3-piperidinylpropan-2-ols possessing potent dual 5-HT1A
      receptor antagonism and serotonin reuptake inhibition was discovered. 1-(1H-Indol
      4-yloxy)-3-(4-benzo[b]thiophen-2-ylpiperidinyl)propan-2-ols exhibited selective
      and high affinities at the 5-HT1A receptor and serotonin reuptake site in vitro.
      In vivo evaluation of this series of compounds demonstrated elevated
      extracellular serotonin levels from the basal and quick recovery of neuron firing
      that was presumably suppressed by the initial acute activation of 5-HT1A
      somatodendritic autoreceptors.

PMID- 16298131
TI  - Optimization of diarylamines as non-nucleoside inhibitors of HIV-1 reverse
      transcriptase.
AB  - Following computational analyses, potential non-nucleoside inhibitors of HIV-1
      reverse transcriptase have been pursued through synthesis and assaying for anti
      viral activity. The general class Het-NH-Ph-U has been considered, where Het is
      an aromatic heterocycle and U is an unsaturated, hydrophobic group. Results for
      compounds with Het=2-thiazoyl and 2-pyrimidinyl are the focus of this report.

PMID- 16298133
TI  - Synthesis and testing of a triaza-cyclopenta[b]phenanthrene scaffold as a DNA
      binding agent.
AB  - A novel DNA binding agent based upon a triaza-cyclopenta[b]phenanthrene scaffold,
      compound 1, has been synthesized. dsDNA binding analysis of this compound using
      the ethidium bromide displacement assay indicated a preference for GC-rich
      sequences. However, equilibrium dialysis experiments against a variety of nucleic
      acids showed that the target compound bound about 20-fold tighter to G-quartet
      DNA than to dsDNA under physiological salt concentrations. The binding of 1 to G
      quartet DNA was verified by the ability of the compound to promote the formation
      of the quartet and to compete with TmPyP4 for binding to the quadruplex. Given
      the importance of G-quartet binding agents in the treatment of cancer and in the
      understanding of drug-DNA interactions, 1 and its related analogs should find
      utility as a new class of G-quartet specific agents.

PMID- 16298132
TI  - Communication interaction in ICU--Patient and staff experiences and perceptions.
AB  - Patients on intensive care units (ICU) have difficulty with communication [Menzel
      LK. Factors related to the emotional responses of intubated patients to being
      unable to speak. Heart Lung 1998; 27(4):245-52]. Feelings of anger and low mood
      have been reported, which can lead to reduced participation in rehabilitation.
      For members of the multidisciplinary team breakdown in communication with
      patients may be frustrating and related to a limited knowledge of strategies and
      resources to facilitate communication. The NHS Modernisation Agency Critical Care
      Programme (2002) identified speech and language therapists (SLTs) as having a
      role in the assessment and management of patients with communication difficulties
      on ICU. This multi-centre pilot study aimed to investigate staff and patient
      perceptions and experiences of communication within ICUs. A short questionnaire
      was devised using semi-structured interviews to collect quantitative and
      qualitative information. Patterns were identified including insights into SLT
      service delivery and possible directions for future research and development.

PMID- 16298134
TI  - Synthesis, cellular uptake and animal toxicity of a tetra(carboranylphenyl)
      tetrabenzoporphyrin.
AB  - A water-soluble nido-carboranyl-tetrabenzoporphyrin has been synthesized in 43%
      overall yield, by condensation of butanopyrrole with a carboranylbenzaldehyde,
      followed by metal insertion, oxidation, demetallation and deboronation reactions.
      This compound accumulated within human glioblastoma T98G cells to a significant
      higher extent than a structurally related nido-carboranylporphyrin, and localized
      preferentially in the cell lysosomes. Animal toxicity studies using male and
      female BALB/c mice revealed that both compounds are non-toxic even at a dose of
      160 mg/kg, administered intraperitoneally as a single injection at a
      concentration of 4 mg/mL. It is concluded that the tetra(carboranylphenyl)
      tetrabenzoporphyrin is a promising new sensitizer for the treatment of malignant
      tumors.

PMID- 16298135
TI  - Detecting axon damage in spinal cord from a mouse model of multiple sclerosis.
AB  - In the current study, the feasibility and reproducibility of in vivo diffusion
      tensor imaging (DTI) of the spinal cord in normal mice are illustrated followed
      by its application to mice with experimental allergic encephalomyelitis (EAE) to
      detect and differentiate axon and myelin damage. Axial diffusivity, describing
      water movement along the axonal fiber tract, in all regions of spinal cord white
      matter from EAE-affected C57BL/6 mice was significantly decreased compared to
      normal mice, whereas there was no statistically significant change in radial
      diffusivity, describing water movement across the fiber tract. Furthermore, a
      direct comparison between DTI and histology from a single mouse demonstrated a
      decrease in axial diffusivity that was supported by widespread staining of
      antibody against beta-amyloid precursor protein. Regionally elevated radial
      diffusivity corresponded with locally diminished Luxol fast blue staining in the
      same tissue from the EAE mouse cord. Our findings suggest that axonal damage is
      more widespread than myelin damage in the spinal cord white matter of mice with
      EAE and that in vivo DTI may provide a sensitive and specific measure of white
      matter injury.

PMID- 16298136
TI  - Regulation of neural cell survival by HIV-1 infection.
AB  - Infection by the lentivirus, human immunodeficiency virus type 1 (HIV-1), results
      in a variety of syndromes involving both the central (CNS) and the peripheral
      (PNS) nervous systems. Productive HIV-1 infection of the CNS is chiefly
      detectable in perivascular macrophages and microglia. HIV-1 encoded transcripts
      and proteins have also been detected in the PNS; however, productive viral
      replication appears to be sparse and restricted to the macrophage cell
      population. Despite the absence of productive infection of neurons, HIV-1
      infection has been associated with neuronal loss in distinct regions of the
      brain. Neuronal cell loss may occur through both necrosis and apoptosis, although
      neuronal apoptosis appears to be a feature of AIDS, as only rare apoptotic
      neurons have been demonstrated in a few pre-AIDS cases. Although there is no
      clear consensus as to the underlying mechanism of HIV-induced neuropathogenesis,
      two complementary concepts predominate. Firstly, HIV-1 encoded proteins injure
      neurons directly without requiring the intermediary functions of nonneuronal
      cells. Alternatively, neuronal apoptosis may result indirectly from the secretion
      of neurotoxic host molecules by resident brain macrophages or microglia in
      response to HIV-1 infection, stimulation by viral proteins or immune activation.
      Herein, we review the neurological disorders and their underlying mechanisms
      associated with HIV infection, focusing on HIV-associated dementia (HAD) and HIV
      sensory neuropathy (HIV-SN). The evidence that neuronal loss in HIV-1-infected
      individuals may be due to neuronal apoptosis is then discussed. This review also
      summarizes the current data supporting both the direct and indirect mechanisms by
      which neuronal death may occur during infection with HIV-1 or the closely related
      lentiviruses SIV and FIV. Lastly, strategies are examined for treating or
      preventing HAD by targeting specific neurotoxic mechanisms.

PMID- 16298137
TI  - Interaction between tumor necrosis factor-alpha and leptin-induced inhibition of
      cardiac contractile function in isolated ventricular myocytes.
AB  - Pro-inflammatory factors such as the adipokine leptin and cytokine tumor necrosis
      factor-alpha (TNFalpha) have been implicated in the onset of myocardial
      dysfunction in ischemia-reperfusion injury, sepsis, heart failure, viral
      myocarditis and cardiac allograft rejection. Although circulating TNFalpha and
      leptin levels are both elevated under a variety of inflammatory conditions, it
      remains unknown whether TNFalpha and leptin depress cardiac contractile function
      independently or synergistically. We examined the effect of acute (30 min) and
      short-term (24h) exposure of TNFalpha, leptin or both on cardiac contractile
      function in adult rat ventricular myocytes. Contractile properties were evaluated
      using an Ionoptix Softedge system including peak shortening (PS), maximal
      velocity of shortening/relengthening (+/-L/t), time-to-PS (TPS) and time-to-90%
      relengthening (TR(90)). Both TNFalpha (0.5-500 pg/ml) and leptin (1-100 nm)
      exerted concentration-dependent inhibitions in PS and +/-L/t following a 30-min
      exposure. TNFalpha but not leptin prolonged TR(90). Interestingly, TNFalpha
      induced depression of cell shortening was masked by leptin and vice versa.
      Following a 24-h incubation, both TNFalpha and leptin significantly inhibited PS
      and +/-L/t without affecting TPS and TR(90). There was no additive or synergistic
      response by the two pro-inflammatory factors. The nitric oxide synthase inhibitor
      l-NMMA abolished depression of myocyte shortening elicited by TNFalpha, leptin or
      both. In summary, this study demonstrated that the inhibitory effect on cardiac
      contraction by TNFalpha and leptin may mask each other and share a common
      mechanism(s), probably dependent on NO.

PMID- 16298138
TI  - T cell dysfunction in cancer: role of myeloid cells and tumor cells regulating
      amino acid availability and oxidative stress.

PMID- 16298140
TI  - Gliopodia extend the range of direct glia-neuron communication during the CNS
      development in Drosophila.
AB  - Midline glia are a source of cues for neuronal navigation and differentiation in
      the Drosophila CNS. Despite their importance, how glia and neurons communicate
      during the development is not fully understood. Here, we examined dynamic
      morphology of midline glia and assessed their direct cellular interactions with
      neurons within the embryonic CNS. Midline glia extend filopodia-like "gliopodia"
      from the onset of axogenesis through the near completion of embryonic neural
      development. The most abundant and stable within the commissures, gliopodia
      frequently contact neurites extending from the neuropil on either side of the
      midline. Misexpression of Rac1N17 in midline glia not only reduces the number of
      gliopodia but also shifts the position of neuropils towards the midline. Midline
      secreted signaling protein Slit accumulates along the surface of gliopodia.
      Mutant analysis supports the idea that gliopodia contribute to its presentation
      on neuronal surfaces at both the commissures and neuropils. We propose that
      gliopodia extend the range of direct glia-neuron communication during CNS
      development.

PMID- 16298139
TI  - Impaired cerebellar functions in mutant mice lacking DNER.
AB  - DNER is a transmembrane protein carrying extracellular EGF repeats and is
      strongly expressed in Purkinje cells (PCs) in the cerebellum. Current study
      indicated that DNER functions as a new Notch ligand and mediates the functional
      communication via cell-cell interaction. By producing and analyzing knockout mice
      lacking DNER, we demonstrate its essential roles in functional and morphological
      maturation of the cerebellum. The knockout mice exhibited motor discoordination
      in the fixed bar and rota-rod tests. The cerebellum from the knockout mice showed
      significant retardation in morphogenesis and persistent abnormality in fissure
      organization. Histochemical and electrophysiological analyses detected that PCs
      retained multiple innervations from climbing fibers (CFs) in the mutant
      cerebellum. Synaptic transmission from parallel fibers (PFs) or CFs to PCs was
      apparently normal, while glutamate clearance at the PF-PC synapses was
      significantly impaired in the mutant mice. Moreover, the protein level of GLAST,
      the glutamate transporter predominantly expressed in Bergmann glia (BG), was
      reduced in the mutant cerebellum. Our results indicate that DNER takes part in
      stimulation of BG maturation via intercellular communication and is essential for
      precise cerebellar development.

PMID- 16298141
TI  - Expression, purification, and renaturation of bone morphogenetic protein-2 from
      Escherichia coli.
AB  - Homodimeric bone morphogenetic protein-2 (BMP-2) is a member of the transforming
      growth factor beta superfamily that has been used for bone grafting. We were
      interested in exploring the functions of BMP-2 in other disease areas and focused
      on expressing and purifying active BMP-2 proteins. We have developed a new
      approach which involves using FoldIt refolding buffer to refold BMP-2 followed by
      a heparin affinity column to separate correctly folded dimer from monomer. A high
      yield of 29.4 mg BMP-2 dimer per gram cell wet weight was achieved. The purified
      BMP-2 dimer was shown to possess the same level of activity as BMP-2 from CHO
      cells as tested by the induction of alkaline phosphatase activity in C2C12 cells.
      This approach has potential application in refolding and purifying other
      homodimeric proteins.

PMID- 16298142
TI  - Functional shikimate dehydrogenase from Mycobacterium tuberculosis H37Rv:
      purification and characterization.
AB  - Tuberculosis (TB) poses a major worldwide public health problem. The increasing
      prevalence of TB, the emergence of multi-drug-resistant strains of Mycobacterium
      tuberculosis, the causative agent of TB, and the devastating effect of co
      infection with HIV have highlighted the urgent need for the development of new
      antimycobacterial agents. Analysis of the complete genome sequence of M.
      tuberculosis shows the presence of genes involved in the aromatic amino acid
      biosynthetic pathway. Experimental evidence that this pathway is essential for M.
      tuberculosis has been reported. The genes and pathways that are essential for the
      growth of the microorganisms make them attractive drug targets since inhibiting
      their function may kill the bacilli. We have previously cloned and expressed in
      the soluble form the fourth shikimate pathway enzyme of the M. tuberculosis, the
      aroE-encoded shikimate dehydrogenase (mtSD). Here, we present the purification of
      active recombinant aroE-encoded M. tuberculosis shikimate dehydrogenase (mtSD) to
      homogeneity, N-terminal sequencing, mass spectrometry, assessment of the
      oligomeric state by gel filtration chromatography, determination of apparent
      steady-state kinetic parameters for both the forward and reverse directions,
      apparent equilibrium constant, thermal stability, and energy of activation for
      the enzyme-catalyzed chemical reaction. These results pave the way for structural
      and kinetic studies, which should aid in the rational design of mtSD inhibitors
      to be tested as antimycobacterial agents.

PMID- 16298143
TI  - Production of bioactive human granulocyte-colony stimulating factor in transgenic
      rice cell suspension cultures.
AB  - Human granulocyte-colony stimulating factor (hG-CSF), a human cytokine, was
      expressed in transgenic rice cell suspension culture. The hG-CSF gene was cloned
      into the rice expression vector containing the promoter, signal peptide, and
      terminator derived from a rice alpha-amylase gene Amy3D. Using particle
      bombardment-mediated transformation, hG-CSF gene was introduced into the calli of
      rice (Oryza sativa) cultivar Dong-jin. Expression of the hG-CSF gene was
      confirmed by ELISA and Northern blot analysis. The amount of recombinant hG-CSF
      accumulated in culture medium from transgenic rice cell suspension culture on the
      sugar starvation was determined by time series ELISA. Biological activity of the
      plant derived hG-CSF was confirmed by measuring the proliferation of the AML-193
      cells, and was similar to that of the commercial Escherichia coli-derived hG-CSF.
      In this paper, we discuss the attractive attributes of using rice cell suspension
      system for the expression of therapeutic recombinant hG-CSF.

PMID- 16298144
TI  - Reliable method to estimate characteristics of sleep and physical inactivity in
      free-living conditions using accelerometry.
AB  - PURPOSE: The purpose of this study is to use a new method to assess the
      characteristics of sleep and diurnal physical inactivity in human beings by means
      of accelerometry, noninvasively and in free-living conditions. METHODS: Forty
      girls and 40 boys aged 13 to 15 years, randomly selected from rural Senegal, wore
      an accelerometer for a 72-hour period during the dry season in 1998 and 2000. An
      algorithm already tested in another study was used to objectively calculate the
      characteristics of sleep and physical inactivity from movement registration
      provided by accelerometry. RESULTS: Adolescent girls slept for a longer time and
      more quietly than adolescent boys (8 hours 45 minutes versus 8 hours 9 minutes).
      Girls were more inactive than boys (4 hours 23 minutes versus 2 hours 49
      minutes). Reliability estimates of physical inactivity period measures were
      excellent (0.74 to 0.78), and those of sleep period and length measures were
      acceptable (0.45 to 0.61). Girls and boys had the same levels of reliability,
      except for sleep efficiency measures. CONCLUSIONS: These findings could be
      explained by the nature and sex division of habitual tasks within the community.
      The accelerometer is a valid and useful epidemiologic tool for measuring
      characteristics of sleep and physical inactivity in free-living conditions. This
      innovative tool opens new prospects in epidemiology and public health, especially
      in the worldwide epidemic of chronic diseases associated with physical inactivity
      and sleep disorders.

PMID- 16298145
TI  - Phylogeny of Ensifera (Hexapoda: Orthoptera) using three ribosomal loci, with
      implications for the evolution of acoustic communication.
AB  - Representatives of the Orthopteran suborder Ensifera (crickets, katydids, and
      related insects) are well known for acoustic signals produced in the contexts of
      courtship and mate recognition. We present a phylogenetic estimate of Ensifera
      for a sample of 51 taxonomically diverse exemplars, using sequences from 18S,
      28S, and 16S rRNA. The results support a monophyletic Ensifera, monophyly of most
      ensiferan families, and the superfamily Gryllacridoidea which would include
      Stenopelmatidae, Anostostomatidae, Gryllacrididae, and Lezina. Schizodactylidae
      was recovered as the sister lineage to Grylloidea, and both Rhaphidophoridae and
      Tettigoniidae were found to be more closely related to Grylloidea than has been
      suggested by prior studies. The ambidextrously stridulating haglid Cyphoderris
      was found to be basal (or sister) to a clade that contains both Grylloidea and
      Tettigoniidae. Tree comparison tests with the concatenated molecular data found
      our phylogeny to be significantly better at explaining our data than three recent
      phylogenetic hypotheses based on morphological characters. A high degree of
      conflict exists between the molecular and morphological data, possibly indicating
      that much homoplasy is present in Ensifera, particularly in acoustic structures.
      In contrast to prior evolutionary hypotheses based on most parsimonious ancestral
      state reconstructions, we propose that tegminal stridulation and tibial tympana
      are ancestral to Ensifera and were lost multiple times, especially within the
      Gryllidae.

PMID- 16298146
TI  - Comparing two evolutionary mechanisms of modern tRNAs.
AB  - All modern tRNA gene families have a high similarity in their primary structure,
      and share the same cloverleaf secondary structure and an inverted L tertiary
      structure, which provide the clues for the study of their origin and evolution.
      There are two important mechanisms of the tRNA sequences evolution. One is point
      mutation, another is complementary duplication method. Both of them are supported
      by some specific examples. To find out the superior one of the two mechanisms or
      find out the most suitable mechanism for modern tRNAs evolution, we constructed
      two types of networks, parallel and antiparallel networks, based on the two
      mechanisms respectively, and then compared the degree distribution and clustering
      coefficient of networks constructed by the tRNA sequences of the single anticodon
      group, single isoaccepting group, and the whole tRNAs group of the two types of
      networks. The result of the comparison seems consistent with the idea that modern
      tRNA sequences evolved primarily by the mechanism of complementary method, and
      point mutation is an important and indispensable auxiliary mechanism during the
      evolutionary event.

PMID- 16298147
TI  - Seasonality of birth in epilepsy: a Southern Hemisphere study.
AB  - A consistent pattern has emerged from research in Northern Hemisphere populations
      indicating differences in the seasonality of birth between patients with epilepsy
      and the general population. This is the first study using similar methodology to
      look at Southern Hemisphere data. The population studied is composed of patients
      discharged from Australian hospitals with a diagnosis of epilepsy, in the period
      1998-1999. The results show a significantly higher incidence of epilepsy in the
      patients born during the Australian winter and summer and a deficit of patients
      born during the spring and fall. This pattern is consistent with the Northern
      Hemisphere findings. This study provides further evidence of the existence of a
      seasonal aetiological agent(s) for epilepsy acting in the perinatal period.

PMID- 16298148
TI  - Primary vascular access.
AB  - Primary vascular access is usually achievable by a distal autogenous arterio
      venous fistula (AVF). This article describes the approach to vascular access
      planning, the usual surgical options and the factors affecting patency.

PMID- 16298149
TI  - The time-dependence of exchange-induced relaxation during modulated radio
      frequency pulses.
AB  - The problem of the relaxation of identical spins 1/2 induced by chemical exchange
      between spins with different chemical shifts in the presence of time-dependent RF
      irradiation (in the first rotating frame) is considered for the fast exchange
      regime. The solution for the time evolution under the chemical exchange
      Hamiltonian in the tilted doubly rotating frame (TDRF) is presented. Detailed
      derivation is specified to the case of a two-site chemical exchange system with
      complete randomization between jumps of the exchanging spins. The derived theory
      can be applied to describe the modulation of the chemical exchange relaxation
      rate constants when using a train of adiabatic pulses, such as the hyperbolic
      secant pulse. Theory presented is valid for quantification of the exchange
      induced time-dependent rotating frame longitudinal T1rho,ex and transverse
      T2rho,ex relaxations in the fast chemical exchange regime.

PMID- 16298151
TI  - Serum amyloid P-component in murine tuberculosis: induction kinetics and
      intramacrophage Mycobacterium tuberculosis growth inhibition in vitro.
AB  - Serum amyloid P-component (SAP), a pentraxin, is known to play an important role
      in innate immunity to microbial infections; however, nothing is known about it
      during tuberculosis (TB). Mice intratracheally infected with Mycobacterium
      tuberculosis Erdman, showed peak SAP levels (442+/-58.2 microg/ml) on day 21,
      which declined to background levels by day 60. Their serum interleukin-6 levels
      paralleled SAP levels, whereas, their serum transforming growth factor-beta
      levels were paradoxical. During the acute phase of infection, the SAP levels
      positively correlated with the lung mycobacterial load. Purified mouse SAP (1-50
      microg/ml) treatment of M. tuberculosis-infected alveolar macrophages (AMs), in
      vitro, inhibited their intracellular mycobacterial growth; maximum inhibition
      (1.1 log10 CFU reduction) occurred at 10 microg/ml, and a 4-day treatment
      appeared optimal. Treatment of AMs with both rabbit anti-mouse SAP polyclonal
      antibody and mannose-derived simple sugars, separately, blocked the SAP-induced
      inhibition of mycobacterial growth. The mycobacterial growth inhibition appeared
      to be nitric oxide (NO)-dependent as NO synthase inhibitors, both aminoguanidine
      and N(G)-monomethyl-L-arginine, annulled it. Further, SAP treatment of infected
      AMs induced significant (P<0.05) elaboration of nitrite (72.1+/-8.3 nM/ml),
      compared to the controls, and these AMs showed augmented expression of inducible
      NO synthase. This first study demonstrates that during murine TB the SAP levels
      were increased, and purified mouse SAP inhibited the intra-AM M. tuberculosis
      growth, in vitro, apparently via NO-dependent mechanism(s). SAP may thus
      contribute both to the pathogenesis and pulmonary innate immunity in TB.

PMID- 16298150
TI  - Dromedary glycosaminoglycans: molecular characterization of camel lung and liver
      heparan sulfate.
AB  - Glycosaminoglycans (GAGs) are the portion of a proteoglycan that determine its
      final shape and function. The molecular structure of predominant GAG species in
      camel liver and lung is reported for the first time. The one-humped camel
      survives in an extreme, arid habitat and, thus, offers a good model to study the
      role of glycomics on homeostasis. Heparan sulfate (HS) from the lung and liver of
      the one-humped camel were isolated. Characterization of these newly isolated
      glycosaminoglycans included (1)H NMR spectroscopy and disaccharide compositional
      analysis. The relative molecular weight of these GAGs was estimated by gradient
      polyacrylamide gel electrophoresis and their degree of sulfation was also
      assessed. Anticoagulant activity was determined using an anti-factor Xa assay and
      the HS from camel lung shows approximately 50% of heparin's activity. The
      structural differences of camel liver GAGs compared to human and porcine liver
      heparin and HS is discussed. Camel lung heparan sulfate resembles both heparin
      and HS in its structure and properties suggesting that it is either a highly
      sulfated form of HS, a mixture of heparin and HS or an undersulfated heparin.

PMID- 16298152
TI  - Influence of culture medium on the resistance and response of Mycobacterium bovis
      BCG to reactive nitrogen intermediates.
AB  - The aim of the present work was to evaluate the influence of the culture medium
      on the resistance and response of Mycobacterium bovis BCG to reactive nitrogen
      intermediates, in vitro. BCG was grown in Sauton, Dubos or Middlebrook 7H9 medium
      and exposed to sodium nitroprusside (SNP) for up to 7 days. The percentage of
      bacilli that survived was significantly lower in Middlebrook 7H9 than in Sauton
      or Dubos medium. Addition of SNP to Middlebrook 7H9 caused an increase in the
      RedOx potential in either the absence or the presence of BCG, while addition of
      the compound to Sauton medium gave rise to an increase in the RedOx potential
      only in the absence of bacteria, whereas a decrease in the RedOx potential was
      observed in the presence of BCG. The resistance of BCG to SNP in the different
      media did not correlate with the concentration of peroxynitrite in culture
      supernatants. BCG grown in different media showed a differential protein
      expression pattern, as assessed by two-dimensional gel electrophoresis. Exposure
      of BCG to sub-lethal concentrations of SNP in Middlebrook 7H9, but not in Sauton
      medium, revealed a differential expression of at least 38 protein species.
      Altogether these results demonstrate that the growth medium may have a remarkable
      influence on the resistance and the response of BCG to SNP and suggest that the
      different resistance of BCG in the two media is unlikely to be due to a
      differential antioxidant effect of the medium itself.

PMID- 16298153
TI  - Two clones obtained from Urabe AM9 mumps virus vaccine differ in their
      replicative efficiency in neuroblastoma cells.
AB  - A high rate of post-vaccinal aseptic meningitis for Urabe AM9 mumps virus strain
      is well documented. This strain is composed of two virus variants differing at
      the nt 1081 (A/G) region in the hemagglutinin-neuraminidase (HN) gene. An
      association of HN-A(1081) variant with neurovirulence has been proposed. In order
      to test for neurotropism we isolated the HN-A(1081) and HN-G(1081) virus variants
      from Urabe AM9 mumps virus vaccine. Sequential passages were performed in monkey
      kidney Vero cells and human neuroblastoma SH-SY5Y cells. Viral replication was
      determined by conventional and real-time RT-PCR. The results show that clone HN
      A(1081) can replicate efficiently in both cell types. However, a defective
      replication of clone HN-G(1081), lacking its genetic marker, was observed after
      the third passage in neuroblastoma cells. Kinetics assays showed that clone HN
      A(1081) replicates faster than clone HN-G(1081). Viral clones were also
      inoculated into the brains of newborn rats. Clone HN-A(1081) replicated 14 times,
      while clone HN-G(1081) merely duplicated its level over the initial inoculum.
      These results suggest that there is a selective replication of HN-A(1081) mumps
      virus variants in cells of nervous origin.

PMID- 16298154
TI  - Recombinant anti-EspA antibodies block Escherichia coli O157:H7-induced attaching
      and effacing lesions in vitro.
AB  - Intimin and EspA proteins are virulence factors expressed by attaching and
      effacing Escherichia coli (AEEC) such as enteropathogenic and enterohaemorrhagic
      E. coli. The EspA protein makes up a filament structure forming part of the type
      III secretion system (TTSS) that delivers effector proteins to the host
      epithelial cell. Bacterial surface displayed intimin interacts with translocated
      intimin receptor in the host cell membrane leading to intimate attachment of the
      bacterium and subsequent attaching and effacing lesions. Here, we have assessed
      the use of recombinant monoclonal antibodies against E. coli O157:H7 EspA and
      intimin for the disruption of AEEC interaction with the host cell. Anti-gamma
      intimin antibodies did not reduce either adhesion of E. coli O157:H7 to host cell
      mono-layers or subsequent host cell actin rearrangement. Anti-EspA antibodies
      similarly had no effect on bacterial adhesion however they had a marked effect
      upon E. coli O157:H7-induced host cell actin rearrangement, where both monoclonal
      and polyclonal antibodies completely blocked cytoskeletal changes within the host
      cell. Furthermore, these anti-EspA antibodies were shown to reduce actin
      rearrangement induced by some but not all other AEEC serotypes tested. Both
      polyclonal and monoclonal antibodies could be used to label E. coli O157 EspA
      filaments and these immunoreagents did not inhibit the formation of such
      filaments. This is the first report of monoclonal antibodies to EspA capable of
      disrupting the TTSS function of E. coli O157:H7.

PMID- 16298155
TI  - Bacterial-protozoa interactions; an update on the role these phenomena play
      towards human illness.
AB  - The usage of water with poor microbiological quality increases the risk of human
      illness. This review discusses and updates current thinking on the nature of the
      interaction between a range of human bacterial pathogens and waterborne protozoa.
      The importance of protozoa acting as protective environments for pathogenic
      bacteria from disinfection and of promoting extended survival in otherwise
      hostile environments is highlighted. The significance of biofilms in water
      systems, and new relationships between Salmonella and Campylobacter and water
      borne protozoa are also discussed. The protection of pathogenic bacteria from
      disinfection within protozoa and/or biofilms has important implications for water
      safety.

PMID- 16298156
TI  - Treating the metabolic syndrome using angiotensin receptor antagonists that
      selectively modulate peroxisome proliferator-activated receptor-gamma.
AB  - The metabolic syndrome, defined as a cluster of visceral obesity, insulin
      resistance, dyslipidemia and elevated blood pressure, is associated with pro
      thrombotic, pro-atherogenic and inflammatory risk factors that predispose to
      cardiovascular disease. Although activators of the peroxisome proliferator
      activated receptors (PPARalpha,gamma,delta) in various combinations are under
      development for treating the metabolic syndrome, they are hampered by adverse
      effects related to increased adipogenesis, weight gain, fluid overload and
      carcinogenesis. The recent discovery that telmisartan and irbesartan,
      antihypertensive angiotensin II type 1 receptor (AT1-R) blockers (ARBs), were
      uniquely capable of activating PPARgamma, has provided a novel approach to
      addressing the multifactorial components of the metabolic syndrome. Both drugs
      have established favorable safety profiles and can activate PPARgamma at
      concentrations potentially achievable at therapeutic doses. Emerging studies have
      revealed that both these drugs have beneficial metabolic profiles. This
      information provides a strategic rationale and pharmacological platform for the
      development of novel dual ARB/PPARgamma agonists to target the metabolic syndrome
      and its cardiovascular sequelae, for which therapy is presently insufficient or
      non-existent. Beneficial effects of these agents include increased energy
      expenditure, improved lipid profile, increased insulin sensitivity, blood
      pressure reduction, and amelioration of the associated pro-inflammatory and pro
      atherogenic risk profiles. The potential benefit for treatment of the metabolic
      syndrome, cardiovascular protection, and prevention of related end-organ
      complications could be of immense clinical value.

PMID- 16298158
TI  - Avoiding errors in the molecular epidemiological analysis of hepatitis B virus
      transmission incidents.

PMID- 16298157
TI  - Improved measurement of dibenzo[a,l]pyrene-induced abasic sites by the aldehyde
      reactive probe assay.
AB  - Dibenzo[a,l]pyrene (DB[a,l]P) induces abundant amounts of depurinating adducts
      that spontaneously dissociate to form abasic sites in DNA. However, several
      previous studies that used the aldehyde-reactive probe (ARP) assay, could not
      verify abasic site formation by DB[a,l]P. Therefore, we examined whether a
      modification of the ARP assay would allow greater quantification of abasic sites.
      A previous study indicated that the abasic site quantification is improved by
      letting ARP trap the nascent abasic sites in cells, before extracting DNA for the
      assay. To test whether the addition of ARP to the DB[a,l]P-DNA adduct-forming
      reaction would improve abasic site quantification, we treated calf thymus DNA
      (0.625 mg/mL) with DB[a,l]P (80 microM) and 3-methylcholanthrene-treated rat
      liver microsomes with or without ARP (3 mM). The inclusion of ARP in the adduct
      forming reaction resulted in significantly greater detection of abasic sites (62
      lesions/10(6) bp versus 3.7 lesions/10(6) bp). DB[a,l]P also induces DNA strand
      breaks. The strand breaks may occur at abasic sites and by other mechanisms, such
      as oxidative damage. ARP/O-methoxyamine-abasic site conjugates are refractory to
      strand breakage, however, ARP or O-methoxyamine (3-10 mM) could only partially
      protect DB[a,l]P-induced DNA degradation, presumably by protecting the abasic
      sites, but not the other strand breaks. These results suggest that if DNA strand
      breakages occur at the abasic sites or at bases flanking them, and the fragments
      are lost during DNA extraction, abasic site estimation could be compromised. To
      obtain an independent line of evidence for abasic site formation in DB[a,l]P
      treated cells, mouse Mbeta16 fibroblasts were treated with DB[a,l]P and O
      methoxyamine. O-Methoxyamine is known to potentiate cytotoxicity of abasic site
      inducing chemicals by forming abasic site conjugates, which partially inhibits
      their repair. O-Methoxyamine was found to increase DB[a,l]P cytotoxicity in these
      cells, supporting the idea that DB[a,l]P formed abasic sites. In summary, the
      inclusion of ARP in the DB[a,l]P-DNA adduct-forming reaction traps and protects
      the nascent abasic sites, allowing an improved quantification of abasic sites.

PMID- 16298159
TI  - Fenofibrate reverses the decline in HDL cholesterol in mice overexpressing human
      phospholipid transfer protein.
AB  - In humans, fibrates are used to treat dyslipidemia, because these drugs lower
      plasma triglycerides and raise HDL cholesterol. Treatment with fibrates lowers
      plasma phospholipid transfer protein (PLTP) activity in humans, but increases
      PLTP activity in mice, without a consistent effect on HDL-cholesterol
      concentration. Earlier, we found that PLTP overexpression in transgenic mice
      results in decreased plasma HDL levels and increased diet-induced
      atherosclerosis. So it seems that the interplay between fibrates, PLTP and HDL is
      different in mice and man, which may be important for atherosclerosis
      development. In the present study, we measured the effects of fibrates on PLTP
      expression in cultured human hepatocytes and effects of fibrate treatment on
      human PLTP expression, plasma PLTP activity and HDL levels in human PLTP
      transgenic mice. Fibrate treatment did not influence PLTP mRNA levels in human
      hepatocytes. Hepatic human PLTP mRNA levels and PLTP activity were both
      moderately elevated by fenofibrate treatment in human PLTP transgenic mice. In
      wild-type mice, however, feeding fenofibrate resulted in a strong induction of
      PLTP mRNA in the liver and a more than 4-fold increase of plasma PLTP activity.
      Plasma triglycerides were reduced in all mice by 48% or more by fenofibrate
      treatment. HDL-cholesterol concentrations were substantially increased by
      fenofibrate in PLTP overexpressing mice (+72%), but unaffected in wild-type mice.
      We conclude that fenofibrate treatment reverses the HDL-lowering effect of PLTP
      overexpression in human PLTP transgenic mice.

PMID- 16298161
TI  - Friend or foe? Antimicrobial peptides trigger pathogen virulence.
AB  - In an age of antibiotic-resistant pathogens, antimicrobial peptides have emerged
      as novel therapeutics hailed for their bactericidal and immunomodulatory
      properties. However, a recent paper by Bader et al. demonstrates that these
      molecules also trigger bacteria to arm themselves against host immune responses.
      The authors show that the two-component regulatory system PhoP-PhoQ of Salmonella
      is activated not only in cation-deficient environments as previously thought, but
      also by binding to antimicrobial peptides, thus promoting gene transcription
      necessary for Salmonella survival within the host. Thus, the antimicrobial
      peptide might be a double-edged sword, promoting antibacterial immunity while
      simultaneously triggering pathogen virulence.

PMID- 16298160
TI  - Injection systems for two luteinising hormone-releasing hormone agonists: a
      comparative assessment of administration times and nurses' perceptions.
AB  - The aim of this study was to compare the speed of administration (preparation and
      delivery) and nurses' perceived ease of use and relative safety of two injection
      systems used to administer luteinising hormone-releasing hormone agonists: a
      depot system used to administer goserelin acetate ('Zoladex', AstraZeneca) and a
      vial system used to administer leuprorelin acetate ('Prostap', Wyeth). This was a
      randomised, crossover study with 82 volunteer nurses (50 pre-registration and 32
      post-registration). All nurses were timed in the administration of both systems
      and all were required to assess the two systems by completing a questionnaire.
      Results indicate that both pre- and post-registration nurses administered the
      depot system in less time than the vial system. Overall mean times for
      administration of the depot system and the vial system were 1.70 and 3.34min,
      respectively. In questionnaire responses, significantly more nurses thought that
      the depot system had 'good safety precautions' compared with the vial system (85%
      versus 40%; P<0.001) and significantly more nurses also expressed a preference
      for the depot system (58% versus 42%; P=0.036). In conclusion, this study
      demonstrates that nurses prefer the one-step depot system used to administer
      goserelin acetate over the vial system used to administer leuprorelin acetate.

PMID- 16298162
TI  - Can symptom presentation predict unstable angina/non-ST-segment elevation
      myocardial infarction in a moderate-risk cohort?
AB  - BACKGROUND: Accurate recognition of acute coronary syndromes (ACS) on initial
      presentation is key to minimizing morbidity and mortality. The wide spectrum of
      symptom presentation in ACS complicates recognition. Unstable angina/non-ST
      elevation myocardial infarction (UA/NSTEMI) may be particularly difficult to
      diagnose as patients often do not exhibit initial high-risk features, leaving the
      clinician with symptom presentation alone, on which to base decisions regarding
      further investigation and treatment. PURPOSE: The aim of this study was to
      compare typical symptom presentation (classic description of angina) and atypical
      presentation in a cohort presenting with symptoms suggestive of UA/NSTEMI.
      METHOD: A prospective cohort design was used to evaluate 100 patients enrolled in
      an Emergency Department Chest Pain Program. RESULTS: Although patients with
      typical presentation were more likely to have UA/NSTEMI, atypical presentation
      did not rule out this diagnosis. Of the 31 patients with UA/NSTEMI, most (n=23,
      74.2%) had atypical symptoms. Male gender, symptom location, and history of
      ischemic heart disease were significantly associated with UA/NSTEMI. Of those
      with a final diagnosis of UA/NSTEMI, there was no difference in symptom
      presentation based on age or gender. CONCLUSION: Clinicians should not rely on
      classic descriptions of angina when evaluating patients suspected of UA/NSTEMI.

PMID- 16298163
TI  - Detecting and aligning peaks in mass spectrometry data with applications to
      MALDI.
AB  - In this paper, we address the peak detection and alignment problem in the
      analysis of mass spectrometry data. To deal with the peak redundancy problem
      existing in the MALDI data acquired in the reflectron mode, we propose to use the
      amplitude modulation technique in peak detection. The alignment of two peak sets
      is formulated as a non-rigid registration problem and is solved using a robust
      point matching (RPM) approach. To align multiple peak sets, we first use a super
      set method to find a common peak set among all peak sets as a standard and then
      align all peak sets to the standard using the robust point matching approach in a
      sequential manner (i.e. We align only one peak set to the standard each time,
      thus reducing the multiple peak set alignment problem to a simpler two peak set
      alignment problem). Experimental results from a study of ovarian cancer data set
      show that the quantitative cross-correlation coefficients among technical
      replicates are increased after peak alignment. Additional comparisons also
      demonstrate that our method has a similar performance as the hierarchical
      clustering method, although the implementations of these methods are different.

PMID- 16298164
TI  - Frequency of diabetes and thyroid autoantibodies in patients with autoimmune
      endocrine disease from Cameroon.
AB  - BACKGROUND: Diabetes is a major cause of morbidity and mortality in both
      industrialized and developing countries. In Africa, there are little data on the
      prevalence and immunological features of patients with autoimmune endocrine
      diseases. AIM OF THE STUDY: The present hospital-based study was carried out to
      evaluate disease-associated autoantibodies in both type 1 diabetes and
      thyrotoxicosis attending the Central Hospital of Yaoundee in Cameroon. PATIENTS
      AND METHODS: Samples were collected from a total of 101 subjects, 47 of whom
      clinically had established type 1 diabetes (mean age 30.1 years +/- 7.6, mean
      disease duration 3.3 years), 18 had thyrotoxicosis (mean age 32.7 years +/- 7.6,
      mean disease duration 6.3 years +/- 2.8) and 36 normal subjects (mean age 26
      years +/- 4.5). All subjects were tested for diabetes-associated glutamic acid
      decarboxylase (GAD) and tyrosine phosphatase (IA2) autoantibodies using antigen
      specific radioimmunoassay as well as thyroiditis-associated thyroglobulin (Tg)
      and thyroid peroxidase (TPO) autoantibodies using commercially available kits.
      RESULTS: Of 47 patients with type 1 diabetes, 16 (34%) had GAD autoantibodies
      (Abs), 3 (6.4%) had IA2 Abs, and 2 (4.3%) had TPO Abs. Of 18 patients with
      thyrotoxicosis 4 (22.2%) had GAD Abs, 5 (27.8%) showed IA2 Abs, while 8 patients
      (44.4%) were TPO Abs positive. No patients in either group had Tg Abs. Among
      normal subjects, 2 (5.6%) showed GAD Abs, and one of these was also IA2 Abs
      positive, but none had thyroid autoantibodies. CONCLUSION: Adult-onset type 1
      diabetic patients some years post-diagnosis from central Africa show GAD, IA2 or
      TPO Abs; and surprisingly, patients with thyrotoxicosis had a similar frequency
      of diabetes-associated autoantibodies. We conclude that, despite a different
      genetic and environmental background to European populations, islet cell
      autoimmunity is common in autoimmune endocrine patients in central Africa.

PMID- 16298165
TI  - Anti-SARS-CoV immunity induced by a novel CpG oligodeoxynucleotide.
AB  - To develop CpG oligodeoxynucleotides (CpG ODNs) based therapy for prevention and
      treatment of severe acute respiratory syndrome (SARS), we selected a novel CpG
      ODN (BW001), which displays B-type CpG ODN structure feature at the 5' and A-type
      CpG ODN structure feature at the 3', and tested for its anti-SARS-CoV activity.
      We found that the supernatants of human PBMCs stimulated by BW001 significantly
      protected Vero cells from SARS-CoV infection. BW001 could stimulate human PBMCs
      and pDCs to secrete high level of IFN-alpha and promote human PBMCs and B cells
      to proliferate. Furthermore, we demonstrated that BW001 could activate CD19+ B
      cells and CD56+ NK cells in human PBMCs. In addition, BW001 could enhance NK
      cytotoxicity and IFN-gamma secretion in human PBMCs. Together, BW001 represents a
      novel type of CpG ODN and may have potential for the development of treatment and
      prevention for SARS as well as other viral associated diseases.

PMID- 16298166
TI  - Recurrent urinary tract infections.
AB  - Urinary tract infection (UTI) is one of the most common bacterial infections in
      women, and one in four of these women will develop a recurrence. Various risk
      factors predispose women of different age groups to recurrence. These factors
      include sexual intercourse, use of contraception, antimicrobials, oestrogen,
      genetics, and the distance of the urethra from the anus. Of the different
      pathogens, Escherichia coli is the organism most commonly isolated. A variety of
      treatment options has been proposed, including long-term or post-intercourse
      prophylaxis and patient-initiated therapy. Oestrogen and cranberry juice have
      also been used as prophylactic treatment adjuncts. At present, other therapeutic
      and preventive modalities are being investigated, including the development of
      vaccines to treat those most severely affected.

PMID- 16298167
TI  - Metabolic biotinylation of lentiviral pseudotypes for scalable paramagnetic
      microparticle-dependent manipulation.
AB  - Nonviral, host-derived proteins on lentiviral vector surfaces can have a profound
      effect on the vector's biology as they can both promote infection and provide
      resistance to complement inactivation. We have exploited this to engineer a
      specific posttranslational modification of a "nonenvelope," virally associated
      protein. The bacterial biotin ligase (BirA) and a modified human DeltaLNGFR have
      been introduced into HEK293T cells and their protein products directed to the
      lumen of the endoplasmic reticulum. The BirA then couples biotin to an acceptor
      peptide that has been fused to the DeltaLNGFR. This results in the covalent
      linkage of biotin to the extracellular domain of the DeltaLNGFR expressed on the
      cell surface. Lentiviral vectors from these cells are metabolically labeled with
      biotin in the presence of free biotin. These biotinylated lentiviral vectors have
      a high affinity for streptavidin paramagnetic particles and, once captured, are
      easily manipulated in vitro. This is illustrated by the concentration of
      lentiviral vectors pseudotyped with either the VSV-G or an amphotropic envelope
      in excess of 4500-fold. This new cell line has the potential for widespread
      application to envelope pseudotypes compatible with lentiviral vector production.

PMID- 16298169
TI  - Thyroid hormone-induced oxidative stress in rodents and humans: a comparative
      view and relation to redox regulation of gene expression.
AB  - Thyroid hormone (3,3',5-triiodothyronine, T(3)) exerts significant actions on
      energy metabolism, with mitochondria being the major target for its calorigenic
      effects. Acceleration of O(2) consumption by T(3) leads to an enhanced generation
      of reactive oxygen and nitrogen species in target tissues, with a higher
      consumption of cellular antioxidants and inactivation of antioxidant enzymes,
      thus inducing oxidative stress. This redox imbalance occurring in rodent liver
      and extrahepatic tissues with a calorigenic response, as well as in hyperthyroid
      patients, is further enhanced by an increased respiratory burst activity in
      Kupffer cells, which may activate redox-sensitive transcription factors such as
      NF-kappaB thus up-regulating gene expression. T(3) elicits an 80-fold increase in
      the serum levels of tumor necrosis factor-alpha (TNF-alpha), which is abolished
      by pretreatment with the antioxidants alpha-tocopherol and N-acetylcysteine, the
      Kupffer-cell inactivator GdCl(3), or an antisense oligonucleotide against TNF
      alpha. In addition, T(3) treatment activates hepatic NF-kappaB, a response that
      is (i) inhibited by antioxidants and GdCl(3) and (ii) accompanied by induced mRNA
      expression of the NF-kappaB-responsive genes for TNF-alpha and interleukin (IL)
      10. T(3) also increases the hepatic levels of mRNA for IL-1alpha and those of IL
      1alpha in serum. Up-regulation of liver iNOS expression is also achieved by T(3),
      through a cascade initiated by TNF-alpha and involving IkappaB-alpha
      phosphorylation and NF-kappaB activation. In conclusion, T(3)-induced oxidative
      stress in the liver enhances the DNA-binding of NF-kappaB and the NF-kappaB
      dependent expression of cytokines and iNOS by actions primarily exerted at the
      Kupffer cell level.

PMID- 16298168
TI  - Serotonin modulation of caudal photoreceptor in crayfish.
AB  - The sixth abdominal ganglion (6th AG) of the crayfish contains two photosensitive
      neurons. This caudal photoreceptor (CPR) displays spontaneous electrical activity
      and phasic-tonic responses to light pulses. In this paper, we analyzed the
      presence of serotonin in the 6th AG and its effects in the modulation of the
      activity of CPR. In the first part of our study, we identified serotonergic
      neurons in the 6th AG by immunostaining using an antibody against serotonin.
      Next, we quantified the serotonin contents in the 6th AG by using liquid
      chromatography. Finally, we searched for serotonergic modulation of the CPR
      electrical activity by using conventional extracellular recordings. We found 13
      immunopositive neurons located in the ventral side of the 6th AG. The mean
      diameter of their somata was 23+/-9 microm. In addition, there was immunopositive
      staining in neuropilar fibers and varicosities. The contents of serotonin and its
      precursors in the 6th AG varied along the 24-h cycle. Its maximum value was
      reached by midday. Topic application of serotonin to ganglia kept in darkness
      increased the CPR spontaneous firing rate and reduced its light responsiveness.
      Both effects were dose-dependent within ED(50) approximately 1 microM and were
      blocked by the 5-HT antagonist methysergide. These observations support the role
      of serotonin as a neurotransmitter or neuromodulator in the CPR of the two
      species of crayfish Procambarus clarkii and Cherax quadricarinatus.

PMID- 16298170
TI  - Potassium transmembrane fluxes in anoxic hepatocytes from goldfish (Carassius
      auratus L.).
AB  - Despite the fact that anoxic goldfish hepatocytes can maintain the transmembrane
      gradients of Na(+), H(+) and Ca(2+), cyanide (CN) intoxication leads to a rapid
      breakdown of K(+) homeostasis. In this study, [(86)Rb(+)] K(+) fluxes across the
      plasma membrane of goldfish hepatocytes were studied in order to identify the
      possible causes of this imbalance. Four minutes of cyanide incubation induced an
      acute and stable 61% decrease of K(+) influx (mostly driven by Na,K-ATPase
      activity), whereas K(+) efflux increased by 24.3%, this imbalance yielding a net
      K(+) efflux of 0.279+/-0.024 nmol 10(-6) cells(-1) min(-1). This uncoupling was
      not observed when glycolytic ATP production was inhibited with iodoacetic acid.
      Although the CN-induced decrease of K(+) influx was fully reversible upon washout
      of the inhibitor, it could not be prevented by any of the following treatments:
      (1) addition of 2% bovine serum albumin, which binds extracellular fatty acids
      known to activate specific K(+) channels; (2) addition of ascorbate, which acts
      as a radical scavenger; (3) inclusion of 5 mM glucose as an extracellular carbon
      source; and (4) removal of medium oxygen (obtained by nitrogen bubbling).
      Regarding the elevation of K(+) efflux in the presence of CN, neither ATP
      dependent K(+) channels nor the KCl cotransporter appeared to be activated,
      whereas BaCl(2), an inhibitor of voltage-gated K(+) channels, decreased K(+)
      efflux of CN-intoxicated cells to control levels. In summary, these results
      indicate that, in goldfish hepatocytes, the CN-induced K(+) imbalance results
      from acute Na,K-ATPase inhibition together with the activation of voltage
      dependent K(+) channels, the latter probably resulting from transient membrane
      depolarization.

PMID- 16298171
TI  - Towards new information resources for public health--from WordNet to
      MedicalWordNet.
AB  - In the last two decades, WordNet has evolved as the most comprehensive
      computational lexicon of general English. In this article, we discuss its
      potential for supporting the creation of an entirely new kind of information
      resource for public health, viz. MedicalWordNet. This resource is not to be
      conceived merely as a lexical extension of the original WordNet to medical
      terminology; indeed, there is already a considerable degree of overlap between
      WordNet and the vocabulary of medicine. Instead, we propose a new type of
      repository, consisting of three large collections of (1) medically relevant word
      forms, structured along the lines of the existing Princeton WordNet; (2)
      medically validated propositions, referred to here as medical facts, which will
      constitute what we shall call MedicalFactNet; and (3) propositions reflecting
      laypersons' medical beliefs, which will constitute what we shall call the
      MedicalBeliefNet. We introduce a methodology for setting up the MedicalWordNet.
      We then turn to the discussion of research challenges that have to be met to
      build this new type of information resource. We build a database of sentences
      relevant to the medical domain. The sentences are generated from WordNet via its
      relations as well as from medical statements broken down into elementary
      propositions. Two subcorpora of sentences are distinguished, MedicalBeliefNet and
      MedicalFactNet. The former is rated for assent by laypersons; the latter for
      correctness by medical experts. The sentence corpora will be valuable for a
      variety of applications in information retrieval as well as in research in
      linguistics and psychology with respect to the study of expert and non-expert
      beliefs and their linguistic expressions. Our work has to meet several
      considerable challenges. These include accounting for the distinction between
      medical experts and laypersons, the social issues of expert-layperson
      communication in different media, the linguistic aspects of encoding medical
      knowledge, and the reliability, volume, and emergence of medical knowledge. The
      work described here has been tested in a small pilot experiment and awaits large
      scale implementation.

PMID- 16298172
TI  - Characterisation of c-Fos expression in the central nervous system of mice
      following right atrial injections of the 5-HT3 receptor agonist phenylbiguanide.
AB  - Cardiopulmonary receptors relay signals to the central nervous system via vagal
      and spinal visceral afferents. To date there are no detailed topographical
      studies in mice indicating the distribution of central neurones activated
      following stimulation of cardiopulmonary afferents. In anaesthetised mice, we
      injected the 5-HT(3) receptor agonist phenylbiguanide (PBG), a drug that is known
      to stimulate cardiopulmonary afferent C-fibres, into the right atrium of the
      heart and mapped c-Fos expression within specific regions of the central nervous
      system. Intra-atrial injection of PBG produced a reflex cardiorespiratory
      response including a pronounced bradycardia and a respiratory depression. Using
      immunohistochemical detection of the protein product of the immediate-early gene
      c-fos, we mapped the brain regions affected by cardiopulmonary 5-HT(3) receptor
      stimulation. Within the nucleus of the solitary tract (nTS) of PBG-injected mice,
      we detected an increased number of c-Fos-positive nuclei in the dorsolateral and
      gelatinous parts at the level of the area postrema (-7.48 mm bregma) but not at
      more rostral or caudal levels (-7.76, -7.20, -6.84 and -6.36 mm bregma) relative
      to vehicle-injected control mice. In addition, c-Fos expression in the crescent
      part of the lateral parabrachial nucleus was decreased in PBG-injected mice
      whereas no significant differences were detected between PBG-injected and control
      mice in the number of c-Fos-positive nuclei in the dorsal part of the lateral
      parabrachial nucleus. PBG injections had no significant effects on the number of
      c-Fos-positive catecholaminergic neurones within the C1/A1, C2/A2, A5, A6 and A7
      cell groups. Likewise, PBG injections had no significant effects on c-Fos
      expression in other central regions involved in cardiorespiratory control or
      cardiorespiratory reflexes (selected non-catecholaminergic nuclei in the medulla
      and midbrain periaqueductal gray, the paraventricular nucleus of the hypothalamus
      and the central nucleus of the amygdala). Identification of specific regions of
      the nTS complex involved in relaying signals from afferent cardiopulmonary C
      fibres to the central nervous system will be useful for future studies aimed at
      understanding neural mechanisms underlying cardiopulmonary reflexes and
      physiological responses to cardiopulmonary disease.

PMID- 16298173
TI  - Application of solid-phase microextraction in the investigation of protein
      binding of pharmaceuticals.
AB  - Protein-drug interactions of seven common pharmaceuticals were studied using
      solid-phase microextraction (SPME). SPME can be used in such investigations on
      the condition that no analyte depletion occurs. In multi-compartment systems
      (e.g. a proteinaceous matrix) only the free portion of the analyte is able to
      partition into the SPME fiber. In addition if no sample depletion occurs, the
      bound drug-free drug equilibria are not disturbed. In the present study seven
      pharmaceuticals (quinine, quinidine, naproxen, ciprofloxacin, haloperidol,
      paclitaxel and nortriptyline) were assayed by SPME. For quantitative purposes
      SPME was validated first in the absence of proteins. Calibration curves were
      constructed for each drug by HPLC-fluorescence and HPLC-UV analysis. SPME was
      combined to HPLC off-line, desorption occurring in HPLC inserts filled with 200
      microL methanol. Binding of each drug to human serum albumin was studied
      independently. Experimental results were in agreement with literature data and
      ultrafiltration experiments, indicating the feasibility of the method for such
      bioanalytical purposes.

PMID- 16298174
TI  - Simultaneous determination of O6-methyl-2'-deoxyguanosine, 8-oxo-7,8-dihydro-2'
      deoxyguanosine, and 1,N6-etheno-2'-deoxyadenosine in DNA using on-line sample
      preparation by HPLC column switching coupled to ESI-MS/MS.
AB  - O(6)-Methyl-2'-deoxyguanosine (O(6)-mdGuo), 8-oxo-7,8-dihydro-2'-deoxyguanosine
      (8-oxodGuo), and 1,N(6)-etheno-2'-deoxyadenosine (epsilondAdo) are promutagenic
      DNA lesions originating from both endogenous and exogenous agents and actions
      (methylation, hydroxylation, lipid peroxidation products). A highly sensitive
      quantitative method was developed to measure these DNA adducts simultaneously,
      using liquid chromatography tandem mass spectrometry with column switching.
      Deuterated O(6)-[(2)H(3)]mdGuo was synthesized and used as internal standard. The
      limits of quantification for O(6)-mdGuo, 8-oxodGuo, and epsilondAdo were 24, 98,
      and 48 fmol on column, respectively. The method showed linearity in the range
      0.24-125 pmol/ml, 0.98-125 pmol/ml, and 0.49-62.5 pmol/ml for the three adducts,
      respectively. The inter-day precision in the linear concentration range was
      between 1.7 and 9.3% for O(6)-mdGuo, 10.6 and 28.7% for 8-oxodGuo, and 6.2 and
      10.4%, for epsilondAdo. In DNA isolated from liver of untreated 12-week-old
      female F344 rats, O(6)-mdGuo was above the limit of detection (37 adducts per
      10(9) normal nucleosides) but could not be quantified. 8-oxodGuo and epsilondAdo
      showed background levels of 500 and 130 adducts per 10(9) normal nucleosides,
      respectively. DNA analyzed 1h after treatment of rats with dimethylnitrosamine by
      oral gavage of 50 microg/kg b.wt. did not affect the levels of 8-oxodGuo and
      epsilondAdo but resulted in 200 O(6)-mdGuo adducts per 10(9) normal nucleosides.
      The method developed will be of use to study the biological significance of
      exogenous DNA adducts as an increment to background DNA damage and the role of
      modulating factors, such as DNA repair.

PMID- 16298175
TI  - Analysis of omeprazole and 5-OH omeprazole in human plasma using hydrophilic
      interaction chromatography with tandem mass spectrometry (HILIC-MS/MS)-
      eliminating evaporation and reconstitution steps in 96-well liquid/liquid
      extraction.
AB  - Bioanalytical methods using liquid/liquid extraction (LLE) and liquid
      chromatography with electrospray tandem mass spectrometry (LC-MS/MS) are widely
      used. The organic extracts need to be evaporated and reconstituted, hampering
      further improvement of throughput and automation. In this study, we demonstrated
      a novel approach of eliminating these two steps in 96-well LLE by using
      hydrophilic interaction chromatography with MS/MS (HILIC-MS/MS) on silica column
      with high organic/low aqueous mobile phase. Omeprazole, its metabolite 5-OH
      omeprazole, and internal standard desoxyomeprazole, were extracted from 0.05 ml
      of human plasma using 0.5 ml of ethyl acetate in a 96-well plate. A portion (0.1
      ml) of the ethyl acetate extract was diluted with 0.4 ml of acetonitrile and 10
      microl was injected onto a Betasil silica column (50 mm x 3.0 mm, 5 microm) and
      detected by API 3000 and 4000 with (+) ESI. Mobile phase with linear gradient
      elution consists of acetonitrile, water, and formic acid (from 95:5:0.1 to
      73.5:26.5:0.1 in 2 min). The flow rate was 1.5 ml/min with total run time of 2.75
      min. The method was validated for a low limit of quantitation at 2.5 ng/ml for
      both analytes. The method was also validated for specificity, reproducibility,
      stability and recovery. Lack of adverse matrix effect and carry-over was also
      demonstrated. The inter-day precision and accuracy of the quality control samples
      at low, medium and high concentration levels were <4.4% relative standard
      deviation (R.S.D.) and 4.1% relative error (R.E.) for omeprazole, and 4.5% R.S.D.
      and 5.6% R.E. for 5-OH omeprazole, respectively.

PMID- 16298176
TI  - Quantitative and qualitative analysis of flavonoid markers in Frucus aurantii of
      different geographical origin by capillary electrophoresis with electrochemical
      detection.
AB  - A capillary electrophoresis with electrochemical detection (CE-ED) method was
      developed for the simultaneous determination of four major flavonoid markers
      (synephrine, naringin, hesperidin and naringenin) in Frucus aurantii of different
      geographical origin. Operated in a wall-jet configuration, a 300 microm diameter
      carbon disc electrode was used as the working electrode, which exhibits a good
      response at +0.85 V (versus saturated calomel electrode) for the analytes. Under
      the optimum conditions, the analytes were baseline separated within 20 min in a
      80 mmol/L borax buffer (pH 8.45). The intra-day relative standard deviations
      (R.S.D.) and inter-day R.S.D.s were based on the analysis of the standard
      solution on the same day and on the following 6 consecutive days. The intra-day
      R.S.D.s ranged from 0.8% (naringin) to 3.6% (hesperidin). The inter-day R.S.D.s
      ranged from 1.2% (hesperidin) to 4.6% (naringenin). Calibration curves were
      linear in ranges between 0.05 and 1000 microg/mL for the markers. Limits of
      detection ranged from a low of 1 x 10(-8)g/mL (hesperidin) to a high of 5 x 10(
      7)g/mL (naringin). The method was successfully used in the analysis of F.
      aurantii of different geographical origin with relatively simple extraction
      procedures, and the assay results were satisfactory.

PMID- 16298177
TI  - Modulation of prion protein structure by pressure and temperature.
AB  - High pressure and temperature have been used efficiently to shed light on prion
      protein structure and folding. These physical parameters induce different
      conformational states of the prion protein, suggesting that prion structural
      changes occur within a complex energy landscape. Pressure has been used to
      prevent and even reverse prion protein aggregation. Alternatively, depending on
      experimental conditions, pressure also promotes prion protein aggregation leading
      to the formation of amorphous aggregates and amyloid fibrils. The latter ones
      show all characteristics of the pathogenic scrapie form. Furthermore, the
      pressure effects on prion protein structure appear to be strongly dependent on
      the integrity of the disulfide bond. In this paper, we discuss the mechanism and
      the origin of these opposing effects of pressure, taking the truncated form of
      hamster prion protein (SHaPrP(90-231)) as a model.

PMID- 16298178
TI  - Prevalence of fractures among the Thalassemia syndromes in North America.
AB  - Historically, fractures are cited as a frequent problem in patients with
      Thalassemia prior to optimization of transfusion and chelation regimens. The aim
      of this study was to determine the prevalence of fractures in a contemporary
      sample of North American patients with Thalassemia. The North American
      Thalassemia Clinical Research Network (TCRN) database registry was used to gather
      historical data on 702 patients with common alpha and beta-Thalassemia diagnoses
      including Thalassemia Major (TM), Intermedia (TI), E/Beta, homozygous alpha
      Thalassemia (AT), Hemoglobin H disease (HbH) and HbH with Constant Spring
      (HbH/CS), who consented to a medical record chart review. Bone mineral density
      (BMD) measurements by DXA were available for review in a subgroup of patients (n
      = 312). The overall fracture prevalence among all Thalassemia syndromes was
      12.1%, equally distributed between females (11.5%) and males (12.7%). Fractures
      occurred more frequently in TM (16.6%) and TI (12.2%) compared to E/Beta (7.4%)
      and alpha (2.3%). Prevalence increased with age (2.5% ages 0-10 years, 7.4% ages
      11-19 years, 23.2% ages >20 years) and with use of sex hormone replacement
      therapy (SHRT) (P < 0.01). On average, BMD Z and T scores were 0.85 SD lower
      among patients with a history of fractures (mean Z/T score -2.78 vs. -1.93, 95%
      CI for the difference -0.49 to -1.22 SD, P = 0.02). Presence of other
      endocrinopathies (i.e. hypothyroidism, hypoparathyroidism and diabetes mellitus),
      anthropometric parameters, heart disease or hepatitis C were not significant
      independent predictors of fractures. These data indicate that fractures remain a
      frequent complication among the aging patients with both TM and TI beta
      Thalassemia. However, the fracture prevalence has improved compared to published
      reports from the 1960s to 1970s. In addition, children with Thalassemia appear to
      have low fracture rates compared to the general population.

PMID- 16298179
TI  - Evaluation of a focused sonication probe for arsenic speciation in environmental
      and biological samples.
AB  - Arsenic speciation analysis suffers in general from high sample handling time
      required by sample preparation. In a previous work, ultrasonic probe has been
      proved to reduce sample treatment time for arsenic extraction in rice to only a
      few minutes. Base upon the obtained results, here several extraction media for
      chicken, fish and soil samples (SEAS G6RD-CT2001-00473) have been studied and
      evaluated employing the same technique. Chicken sample needed an enzymatic
      treatment in order to liberate the species linked to the protein matrix.
      Extraction of the major species in fish, AsB, was quantitatively achieved in
      water in 1 min. Also 1 min was enough to leach about 85% of species present in
      soils and sediments, mainly the inorganic ones, using H(3)PO(4). In all cases, no
      inter-conversion among As species was observed. The five species found in those
      samples were separated using an improved HPLC-ICP-MS method in only 11 min, with
      detection limits at the ng l(-1) level. The proposed methods were validated by
      analysing several Certified Reference Materials: SRM 1,568 a rice flour, CRM-627
      tuna fish tissue, SOIL-7 soil and MURST-ISS-A1 Antarctic sediment.

PMID- 16298180
TI  - Calibration of solid-phase micro-extraction for quantitative analysis by gas
      chromatography.
AB  - Calibration of SPME by the injection of liquid standard solution is a common
      method for SPME quantitative analysis by gas chromatography. The feasibility of
      this calibration method relies on the assumption that sample transfer
      efficiencies are the same for both the liquid injection and the SPME fiber
      injection. Sample transfer efficiencies for liquid injection and SPME fiber
      injection were studied in this paper. The results showed that the sample transfer
      efficiency for liquid injection was affected by several factors, such as the
      dimensions of the liner, the presence of the wool, and the temperature of the
      injector. The sample transfer efficiency for SPME fiber injection was affected by
      the cross-sectional area of the space between the column and the liner, the
      carrier gas flow rate, and the length of the column inside the liner. An equation
      was proposed to estimate the sample loss rate for SPME injection. It was found
      that the use of a direct injection (DI) liner and program temperature vaporizing
      provides high sample transfer efficiencies, for both liquid injection and SPME
      fiber injection. When a common SPME straight liner is used, large outer diameter
      (o.d.) pre-column will help to achieve high sample transfer efficiency.

PMID- 16298181
TI  - Concentration of organic compounds in natural waters with solid-phase dispersion
      based on advesicle modified silica prior to liquid chromatography.
AB  - The ability of vesicle-coated silica to aid the extraction of organic compounds
      from water prior to liquid chromatographic analysis is presented for the first
      time. The method is based on the formation of silica supported cationic multi
      lamellar vesicles of gemini surfactants inherently ensuring the presence of
      hydrophilic and hydrophobic sites for the partitioning of analytes bearing
      different properties. Method development is illustrated by studying the
      adsolubilization of UV absorbing chemicals from swimming pool water. Due to the
      requirement for external energy input (intense shearing) a method based on solid
      phase dispersion (SPD) was applied producing better results than off-line solid
      phase extraction (SPE). Meticulous investigation of the experimental parameters
      was conducted in order to elucidate the mechanisms behind the proposed extraction
      pattern. Analyte recoveries were quantitative under the optimum experimental
      conditions offering recoveries higher than 96% with RSD values below 5%.

PMID- 16298182
TI  - Simultaneous determination of tetrabromobisphenol A, tetrachlorobisphenol A,
      bisphenol A and other halogenated analogues in sediment and sludge by high
      performance liquid chromatography-electrospray tandem mass spectrometry.
AB  - A high performance liquid chromatography-electrospray (negative) ionization
      tandem mass spectrometry (HPLC-ESI(-)-MS-MS) based method has been developed for
      simultaneous determination of bisphenol A (BPA), tetrachlorobisphenol A (TCBPA),
      and tetrabromobisphenol A (TBBPA), as well as lower brominated BPA analogues in
      sediment and sludge samples. Samples were extracted with MTBE, target compounds
      were partitioned by aqueous solution of sodium hydroxide. The solution was
      subsequently acidified, and the enrichment and desalting were performed via solid
      phase extraction (SPE). After cleanup the target compounds were determined by
      HPLC-ESI(-)-MS-MS. The method limits of quantification (MLOQs) from sediment and
      sludge for BPA, monobromo-bisphenol A (mono-BBPA), dibromo-bisphenol A (di-BBPA),
      tribromo-bisphenol A (tri-BBPA), TBBPA and TCBPA were 0.15, 0.02, 0.02, 0.04,
      0.05, and 0.03 ng/g (dry weight), respectively. Mean recovery of the analytes
      from spiked samples ranged from 70 to 105%, and the relative standard deviation
      ranged from 4.9 to 13.1%. The method was successfully applied to sediment and
      sludge samples analysis.

PMID- 16298183
TI  - Preparative isolation and purification of five compounds from the Chinese
      medicinal herb Polygonum cuspidatum Sieb. et Zucc by high-speed counter-current
      chromatography.
AB  - High-speed counter-current chromatography (HSCCC) was applied to the separation
      and purification of five compounds from the Chinese medicinal herb Polygonum
      cuspidatum Sieb. et Zucc. The crude extracts from P. cuspidatum Sieb. et Zucc
      were treated with light petroleum-ethyl acetate-methanol-water (2:5:4:6, v/v).
      Sample 1 was obtained from the lower phase and sample 2 from the upper phase. The
      sample 1 was separated with light petroleum-ethyl acetate-water (1:5:5, v/v) and
      yielded 19.3mg of piceid, 17.6 mg of anthraglycoside B from 200mg of sample 1.
      The sample 2 was separated with light petroleum-ethyl acetate-methanol-water
      (3:5:4:6, v/v) and light petroleum-ethyl acetate-methanol-water (3:5:7:3, v/v) in
      a gradient elution and yielded 18.5mg of resveratrol, 35.3mg of emodin and 8.2mg
      of physcion from 220 mg of sample 2. The purity of each compound is over 95% as
      determined by HPLC. The chemical structures of these components were identified
      by (1)H NMR and (13)C NMR.

PMID- 16298184
TI  - Simultaneous extraction and analysis of 11 tetracycline and sulfonamide
      antibiotics in influent and effluent domestic wastewater by solid-phase
      extraction and liquid chromatography-electrospray ionization tandem mass
      spectrometry.
AB  - Wastewater treatment plants (WWTPs) in which antibiotic compounds are not totally
      eliminated are considered to be point sources of antibiotic contamination in
      surface and ground waters. Therefore, there is a need for sensitive and reliable
      analytical methods for measuring these compounds in WWTP water matrices. This
      paper describes a simultaneous method for the determination of six tetracyclines
      (TCs) (oxytetracycline (OTC), tetracycline (TC), demeclocycline (DMC),
      chlortetracycline (CTC), doxycycline (DXC), meclocycline (MCC)) and five
      sulfonamides (SAs) (sulfathiazole (STZ), sulfamethazine (SMT),
      sulfachloropyridazine (SCP), sulfamethoxazole (SMX) and sulfadimethoxine (SDM))
      using solid-phase extraction followed by liquid chromatography-ion trap tandem
      mass spectrometry. The average recovery of 11 antibiotics for simultaneous
      extraction was 83.3+/-12.6 and 89.8+/-11.5% for six TCs, and 95.2+/-11.4 and
      97.7+/-10.6% for five SAs in the influent and effluent water, respectively.
      Matrix effects were found to be significant when measuring TCs but not SAs. The
      accuracy and day-to-day variation of the method fell within an acceptable range
      of 15% absolute. Method detection limits in wastewater matrices were between 0.03
      and 0.07 microg/L. For the investigated 11 antibiotic compounds TC, DMC, CTC,
      DXC, SMT, SMX and SDM were found in the influents with a concentration range of
      0.05-1.09 microg/L. CTC, DXC and SMX were also detected in the effluents with a
      concentration range of 0.06-0.21 microg/L. These results were compared with those
      in WWTP effluents of Canada, Germany and Switzerland.

PMID- 16298185
TI  - Reversed-phase high-performance liquid chromatography purification of methyl
      esters of C(16)-C(28) polyunsaturated fatty acids in microalgae, including
      octacosaoctaenoic acid [28:8(n-3)].
AB  - A preparative reversed-phase (RP; C(18)) high-performance liquid chromatography
      (HPLC) method with gradient elution using acetonitrile (MeCN)-chloroform
      (CHCl(3)) (or dichloromethane (DCM)) and evaporative light-scattering detection
      (ELSD) with automatic multiple injection and fraction collection was used to
      purify milligram quantities of microalgal polyunsaturated fatty acids (PUFA),
      separated as methyl esters (ME). PUFA-ME purified included methyl esters of
      docosahexaenoic acid (DHA; 22:6(n-3)), eicosapentaenoic acid (EPA; 20:5(n-3)) and
      the unusual very long-chain (C(28)) highly unsaturated fatty acid (VLC-HUFA),
      octacosaoctaenoic acid [28:8(n-3)(4, 7, 10, 13, 16, 19, 22, 25)] from the marine
      dinoflagellate Scrippsiella sp. CS-295/c. Other PUFA purified from various
      microalgae using this RP-HPLC method to greater than 95% purity included 16:3(n
      4), 16:4(n-3), 16:4(n-1) and 18:5(n-3). The number of injections required was
      variable and depended on the abundance of the desired PUFA-ME, and resolution
      from closely eluting PUFA-ME, which determined the maximum loading. The purity of
      these fatty acids was determined by electron impact (EI) GC-MS and the chain
      length and location of double bonds was determined by EI GC-MS of 4,4-dimethyl
      oxazoline (DMOX) derivatives formed using a low temperature method. Advantages
      over silver-ion HPLC for purifying PUFA-ME is that separation occurs according to
      chain length as well as degree of unsaturation enabling separation of PUFA-ME
      with the same degree of unsaturation but different chain length (i.e. between
      18:5(n-3) and 20:5(n-3)). In addition, PUFA-ME are not strongly adsorbed, but
      elute earlier than their more saturated corresponding FAME of the same chain
      length. This method is robust, simple, and requires only a short re-equilibration
      time. It is a useful tool for preparing milligram quantities of pure PUFA-ME for
      bioactive screening (as free fatty acids), although many multiple injections may
      be required for minor PUFA-ME. It also enabled dose-response and structure
      activity studies to be carried out. It can be used for the enrichment of low
      levels of VLC-HUFA-ME to facilitate elucidation of their chemical structure and
      so is a useful adjunct to EI GC-MS of DMOX derivatives and other techniques such
      as NMR, which requires milligram quantities of purified compounds.

PMID- 16298186
TI  - High performance liquid chromatography-tandem mass spectrometry of phospholipid
      molecular species in eggs from hens fed diets enriched in seal blubber oil.
AB  - The total lipid fraction of eggs from hens fed diets enriched in seal blubber oil
      (1.25-5.0% SBO) was directly analysed with normal-phase high performance liquid
      chromatography coupled on-line with electrospray ionization ion-trap tandem mass
      spectrometry (HPLC-ESI-MS-MS) for the identification of the molecular species of
      phospholipids (PLs). The species of phosphatidylethanolamine (PE) and
      phosphatidylinositol (PI) were all detected as the [M-H](-) ions. The
      phosphatidylcholine (PC), sphingomyelin (Sph) and lysophosphatidylcholine (LPC)
      classes, were detected as formate adducts [M+HCOO](-). Tandem MS of PE and PI
      showed the loss of the carboxylate anions, and, for PI, also the loss of water
      and inositol. Product ion spectrum of PC, LPC and Sph contained only the [M
      CH(3)](-) ion fragment. Feeding different levels of SBO for 5 weeks resulted in a
      significant increase of PE, PC and PI molecular species carrying eicosapentaenoic
      acid (C(20:5 omega3), EPA), docosapentaenoic acid (C(22:5 omega3), DPA) and
      docosahexaenoic acid (C(22:6 omega3), DHA), but not Sph nor LPC. The highest
      increase of the omega3/omega6 ratio occurred for PE and PC. On the contrary, PI
      was less affected by the increase of SBO in the diet.

PMID- 16298187
TI  - Solid-phase extraction coupled with liquid chromatography-tandem mass
      spectrometry for determination of trace rosiglitazone in urine.
AB  - This project evaluated solid-phase extraction (SPE) combined with liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) to determine the trace amount
      of rosiglitazone in human urine. The analytical performance of four modes of LC
      MS and tandem MS operation (atmospheric pressure chemical ionization (APCI),
      electrospray ionization (ESI), positive and negative ionization) was compared for
      two mass spectrometers, a triple-quadrupole and a quadrupole ion trap instrument.
      Rosiglitazone was extracted from urine using a SPE cartridge of 50mg C8 sorbent
      and acetonitrile used as the eluting solvent. Samples were then separated on a
      RP18 column interfaced with a tandem mass spectrometer. The recovery of
      rosiglitazone was greater than 91.2%. The urine assay combining SPE and LC-APCI
      MS/MS of triple-quadrupole was proved a very selective and sensitive method for
      determination of trace rosiglitazone. The assay was linear over a wide range,
      with a lower limit of quantification of 0.1 ng/mL using 1 mL of urine. The intra-
      and inter-day precisions were <9.8% and <7.9%, respectively, and the accuracies
      were in the range 91.0-103.6%. The rosiglitazone concentration profile in human
      urine was also determined. The results of this study reveal the adequacy of SPE
      LC-APCI-MS/MS method for analyzing rosiglitazone from diabetic patients' urines.
      The concentrations of rosiglitazone were detected to range from 760 to 164 pg/mL.

PMID- 16298188
TI  - Thermodynamic functions and intra-particle mass transfer kinetics of structural
      analogues of a template on molecularly imprinted polymers in liquid
      chromatography.
AB  - The parameters of the thermodynamics and mass transfer kinetics of the structural
      analogues (L-enantiomers) of the template were measured on an Fmoc-L-tryptophan
      (Fmoc-L-Trp) imprinted polymer, at different temperatures. The equilibrium
      isotherm data and the overloaded band profiles of these compounds were measured
      at temperatures of 298, 313, 323, and 333 K. The isotherm data were modeled. The
      thermodynamic functions of the different adsorption sites were derived from the
      isotherm parameters, using van't Hoff plots. The mass transfer parameters were
      derived by comparing the experimental peak profiles and profiles calculated using
      the lumped pore diffusion (POR) model for chromatography. These data show that
      (1) the strength between the substrate molecules and the MIP increases with
      increasing number of functional groups on the substrates; (2) enthalpy is the
      driving force for the affinity of the substrates for the MIP; (3) surface
      diffusion is the dominant mass transfer mechanism of the substrates through the
      porous MIP. For those substrate molecules that have the same stereochemistry as
      the template, the energetic surface heterogeneity needs to be incorporated into
      the surface diffusion coefficients. Heterogeneous surface diffusivities decrease
      with increasing affinity of the substrates for the MIP.

PMID- 16298189
TI  - Systematic errors in the measurement of adsorption isotherms by frontal analysis
      Impact of the choice of column hold-up volume, range and density of the data
      points.
AB  - Besides the accuracy and the precision of the measurements of the data points,
      several important parameters affect the accuracy of the adsorption isotherms that
      are derived from the data acquired by frontal analysis (FA). The influence of
      these parameters is discussed. First, the effects of the width of the
      concentration range within which the adsorption data are measured and of the
      distribution of the data points in this range are investigated. Systematic
      elimination of parts of the data points before the calculation of the nonlinear
      regression of the data to the model illustrates the importance of the numbers of
      data points (1) within the linear range and (2) at high concentrations. The
      influence of the inaccuracy of the estimate of the column hold-up volume on each
      adsorption data point, on the selection of the isotherm model, and on the best
      estimates of the adsorption isotherm parameters is also stressed. Depending on
      the method used to measure it, the hold-up time can vary by more than 10%. The
      high concentration part of the adsorption isotherm is particularly sensitive to
      errors made on t(0,exp) and as a result, when the isotherm follows bi-Langmuir
      isotherm behavior, the equilibrium constant of the low-energy sites may change by
      a factor 2. This study shows that the agreement between calculated and
      experimental overloaded band profiles is a necessary condition to validate the
      choice of an adsorption model and the calculation of its numerical parameters but
      that this condition is not sufficient.

PMID- 16298190
TI  - Characterization of the mechanical properties of polymeric chromatographic
      particles by micromanipulation.
AB  - Chromatographic particles should not possess only desirable surface chemical
      properties but also mechanical properties. The latter determine the deformation
      of the particles under hydrodynamic conditions of packed beds and further the
      pressure drop. Understanding the mechanical properties of chromatographic
      particles is essential to successful design and operation of such processing
      equipment. The mechanical properties of single chromatographic particles made of
      different formulations and with different surface modifications were
      characterized by a novel micromanipulation technique. The principle of this
      technique is to compress single particles between two parallel surfaces. The
      force being imposed on the particles and their deformation under compression are
      measured simultaneously. The particles range from 30 to 300 microm, depending on
      their formulation. 10-30 particles from each sample were compressed up to a
      particle deformation of 70% in order to get statistically representative data.
      Particles for hydrophobic interaction chromatography were proved more stable than
      resins for ion exchange or gel filtration. The difference is remarkable in dry
      state and is less in wet state. Water seems to "level out" the differences in
      mechanical stability of resins. The stability seems to be also dependent on the
      speed of water release out of the resins.

PMID- 16298191
TI  - Impact of methanol and acetonitrile on separations based on pi-pi interactions
      with a reversed-phase phenyl column.
AB  - Studies were performed to investigate the roles of methanol and acetonitrile on
      the retention mechanism of an active pharmaceutical ingredient (API) and related
      compounds with a reversed phase phenyl column. Different retention orders were
      observed depending upon whether acetonitrile or methanol was used as the organic
      modifier. We propose that acetonitrile impedes the selective pi-pi interactions
      between the analyte molecules and the phenyl groups in the stationary phase.
      Further study with 1-naphthoic acid and 1-naphthol as test compounds in the HPLC
      separation provides additional support for the influence of acetonitrile on pi-pi
      interactions between analyte molecules and a phenyl stationary phase. This study
      suggests that methanol be used as the preferred organic modifier with phenyl
      columns to achieve selectivity based upon pi-pi interactions.

PMID- 16298192
TI  - Identification of oligomers in polyethyleneterephthalate bottles for mineral
      water and fruit juice. Development and validation of a high-performance liquid
      chromatographic method for the determination of first series cyclic trimer.
AB  - Cyclic oligomers were identified in PET bottles used for mineral water and fruit
      juice using MS and (1)H and (13)C NMR: a first series cyclic trimer, a first
      series cyclic tetramer, a first series cyclic dimmer and a second series cyclic
      trimer. An analytical method to determine first series cyclic trimer in these
      bottles was developed and validated, using HPLC. The first series cyclic trimer
      levels were 316-462 mg/100g of PET bottle.

PMID- 16298193
TI  - Fully automated online solid phase extraction coupled directly to liquid
      chromatography-tandem mass spectrometry. Quantification of sulfonamide
      antibiotics, neutral and acidic pesticides at low concentrations in surface
      waters.
AB  - A fully automated online solid phase extraction-liquid chromatography-tandem mass
      spectrometry (SPE-LC-MS/MS) instrumental setup has been developed for the
      quantification of sulfonamide antibiotics and pesticides in natural water. The
      direct coupling of an online solid phase extraction cartridge (Oasis HLB) to LC
      MS/MS was accomplished using column switching techniques. High sensitivity in the
      low ng/L range was achieved by large volume injections of 18 mL with a
      combination of a tri-directional auto-sampler and a dispenser system. This setup
      allowed high sample throughput with a minimum of investment costs. Special
      emphasis was placed on low cross contamination. The chosen approach is suitable
      for research as well as for monitoring applications. The flexible instrumental
      setup was successfully optimised for different important groups of bioactive
      chemicals resulting in three trace analytical methods for quantification of (i)
      sulfonamide antibiotics and their acetyl metabolites; (ii) neutral pesticides
      (triazines, phenylureas, amides, chloracetanilides) and (iii) acidic pesticides
      (phenoxyacetic acids and triketones). Absolute extraction recoveries from 85 to
      112% were obtained for the different analytes. More than 500 samples could be
      analyzed with one extraction cartridge. The inter-day precision of the method was
      excellent indicated by relative standard deviations between 1 and 6%. High
      accuracy was achieved by the developed methods resulting in maximum deviation
      relative to the spiked amount of 8-15% for the different analytes. Detection
      limits for various environmental samples were between 0.5 and 5 ng/L. Matrix
      induced ion suppression was in general smaller than 25%. The performance of the
      online methods was demonstrated with measurements of concentration dynamics of
      sulfonamide antibiotics and pesticides concentrations in a little creek during
      rain fall events.

PMID- 16298194
TI  - Study of the selectivity of reversed-phase columns for the separation of
      polycarboxylic acids and polyphenol compounds.
AB  - A systematic investigation was undertaken into the relative separation
      performance of five reversed-phase chromatography columns including some
      commercially new hybrid packed columns for a series of polycarboxylic acids and
      polyphenol compounds. Information theory (IT) and factor analysis (FA), together
      with a basic evaluation of retention information (band shape, retention factor
      and elution order) were used to compare four columns to a conventional C18
      column. The results revealed very little difference in retention behaviour
      between the Phenomenex Aqua C18 column, the Waters XTerra RP C18 column, and the
      conventional Phenomenex Luna C18 column. However, there were notable differences
      in the retention processes between the Phenomenex Synergi polar-RP column, which
      is an ether-linked phenyl base with polar endcapping, and the Luna C18 column.
      The most significant differences were observed between the Luna C18 column and a
      Phenomenex Luna Cyano column. However, the limited degree of retention of the
      polycarboxylic acids and polyphenol compounds on the Luna Cyano column permits
      only limited use for the separation of these types of compounds. Overall, the
      Phenomenex Synergi polar-RP column exhibited the best performance for the
      separation of the test solutes compared to that of the conventional C18 column,
      with IT yielding an Informational Similarity of 0.99 and FA a moderate
      correlation coefficient of 0.70. The Phenomenex Synergi polar-RP column gave the
      best peak shape and offered substantial selectivity differences thereby providing
      a good alternative over the conventional C18 column for separating polycarboxylic
      acids and polyphenols.

PMID- 16298195
TI  - Refined non-steady-state gas-liquid chromatography for accurate determination of
      limiting activity coefficients of volatile organic compounds in water:
      application to C(1)-C(5) alkanols.
AB  - This work presents a new refined method of non-steady-state gas-liquid
      chromatography (NSGLC) suitable for determination of limiting activity
      coefficients of VOCs in water. The modifications done to the original NSGLC
      theory address its elements (as the solvent elution rate from the column) as well
      as other new aspects. The experimental procedure is modified accordingly, taking
      advantage of current technical innovations. The refined method is used
      systematically to determine limiting activity coefficients (Henry's law
      constants, limiting relative volatilities) of isomeric C(1)-C(5) alkanols in
      water at 328.15K. Applied to retention data measured in this work the refined
      NSGLC theory gives values 15-20% higher than those from the original approach.
      The values obtained by the refined NSGLC method agree very well (typically within
      3%) with the most reliable literature data determined by other experimental
      techniques, this result verifying thus the correct performance of the refined
      method and demonstrating an improved accuracy of the new results.

PMID- 16298196
TI  - Gas chromatographic ion trap mass spectrometry determination of zoxamide residues
      in grape, grape processing, and in the fermentation process.
AB  - A gas chromatographic ion-trap mass spectrometry (GC-ITMS) method was developed
      for the determination of the fungicide zoxamide in grape, must, wine, and
      spirits. Samples were extracted with hexane and analyzed without any clean up.
      The gas chromatograph was fitted with a carbofrit inserted into the glass liner
      to allow large volume injections. Analyses were carried out both in EI and CI
      mode. Recoveries from fortified samples ranged between 86 and 114% at four
      different fortification levels (n=6 each), ranging between 0.05 and 2.00 mg/kg.
      The relative standard deviation was below 19%. Both in EI and CI mode the
      calculated limit of detection (LOD) and quantification (LOQ) were 0.01 and 0.05
      mg/kg (0.08 mg/kg in CI), respectively. Moreover the influence of yeasts and
      bacteria fermentation was evaluated.

PMID- 16298198
TI  - Fear of avian influenza is a double-edged sword.

PMID- 16298199
TI  - Reducing the burden of stroke.

PMID- 16298197
TI  - Design and evaluation of a coupled monolithic pre-concentrator-capillary zone
      electrophoresis system for the extraction of immunoglobulin G from human serum.
AB  - The analysis of proteins in biological fluids by capillary electrophoresis (CE)
      is of interest in clinical chemistry. However, due to low analyte concentrations
      and poor concentration limits of detection (CLOD), protein analysis by this
      technique is frequently challenging. Coupling preconcentration techniques with CE
      greatly improves the CLOD. An on-line preconcentration-CE method that can
      selectively pre-concentrate any protein for which an antibody is available would
      be very useful for the analysis of low abundance proteins and would establish CE
      as a major tool in biomarker discovery. To accomplish this, the development of an
      on-line protein G monolithic pre-concentrator-CE device is proposed. To generate
      active groups for protein immobilization, glycidyl methacrylate (GMA) was used to
      prepare polymer monoliths. A 1.5-2 cm monolith was cast inside a 75 microm I.D.
      fused silica capillary that had previously been coated with alternating layers of
      negatively (dextran) and positively (polybrene) charged polymers. Protein G was
      covalently bound to GMA. Monoliths from different formulations were prepared and
      evaluated for binding capacity to optimize the monolith formulation for protein
      preconcentration. The physical properties of the column considered best for
      preconcentration were determined by mercury intrusion porosimetry. The total pore
      area was 4.8m(2)/g, the average pore diameter was 3.3 microm and the porosity was
      82%. The monolith had a low flow resistance and was macroscopically homogeneous.
      The effectiveness of the monolith to rapidly pre-concentrate proteins at flow
      rates as high as 10 microL/min was demonstrated using a 1.8 microM IgG solution.
      This system proved effective for on-line sample extraction, clean-up,
      preconcentration, and CE of IgG in human serum. IgG from diluted (500 and 65,000
      times) human serum samples was successfully analyzed using this system. The
      approach can be applied to the on-line preconcentration and analysis of any
      protein for which an antibody is available.

PMID- 16298200
TI  - Public-private partnerships for neglected diseases.

PMID- 16298201
TI  - Vascular disease of the heart, brain and limbs: new insights into a looming
      epidemic.

PMID- 16298202
TI  - Fabry's disease--an important risk factor for stroke.

PMID- 16298203
TI  - Supplement and stimulation for stunted children.

PMID- 16298204
TI  - EVIPNet: translating the spirit of Mexico.

PMID- 16298205
TI  - Cochrane Collaboration and the evolution of evidence.

PMID- 16298206
TI  - Autopsy.

PMID- 16298207
TI  - Robert Lanza. Interview.

PMID- 16298208
TI  - The MANTRA II study.

PMID- 16298209
TI  - The MANTRA II study.

PMID- 16298211
TI  - Lyme disease: scratching the surface.

PMID- 16298212
TI  - Risks and benefits of DDT.

PMID- 16298214
TI  - Population-based study of event-rate, incidence, case fatality, and mortality for
      all acute vascular events in all arterial territories (Oxford Vascular Study).
AB  - BACKGROUND: Acute coronary, cerebrovascular, and peripheral vascular events have
      common underlying arterial pathology, risk factors, and preventive treatments,
      but they are rarely studied concurrently. In the Oxford Vascular Study, we
      determined the comparative epidemiology of different acute vascular syndromes,
      their current burdens, and the potential effect of the ageing population on
      future rates. METHODS: We prospectively assessed all individuals presenting with
      an acute vascular event of any type in any arterial territory irrespective of age
      in a population of 91 106 in Oxfordshire, UK, in 2002-05. FINDINGS: 2024 acute
      vascular events occurred in 1657 individuals: 918 (45%) cerebrovascular (618
      stroke, 300 transient ischaemic attacks [TIA]); 856 (42%) coronary vascular (159
      ST-elevation myocardial infarction, 316 non-ST-elevation myocardial infarction,
      218 unstable angina, 163 sudden cardiac death); 188 (9%) peripheral vascular (43
      aortic, 53 embolic visceral or limb ischaemia, 92 critical limb ischaemia); and
      62 unclassifiable deaths. Relative incidence of cerebrovascular events compared
      with coronary events was 1.19 (95% CI 1.06-1.33) overall; 1.40 (1.23-1.59) for
      non-fatal events; and 1.21 (1.04-1.41) if TIA and unstable angina were further
      excluded. Event and incidence rates rose steeply with age in all arterial
      territories, with 735 (80%) cerebrovascular, 623 (73%) coronary, and 147 (78%)
      peripheral vascular events in 12 886 (14%) individuals aged 65 years or older;
      and 503 (54%), 402 (47%), and 105 (56%), respectively, in the 5919 (6%) aged 75
      years or older. Although case-fatality rates increased with age, 736 (47%) of
      1561 non-fatal events occurred at age 75 years or older. INTERPRETATION: The high
      rates of acute vascular events outside the coronary arterial territory and the
      steep rise in event rates with age in all territories have implications for
      prevention strategies, clinical trial design, and the targeting of funds for
      service provision and research.

PMID- 16298215
TI  - Causes of cancer in the world: comparative risk assessment of nine behavioural
      and environmental risk factors.
AB  - INTRODUCTION: With respect to reducing mortality, advances in cancer treatment
      have not been as effective as those for other chronic diseases; effective
      screening methods are available for only a few cancers. Primary prevention
      through lifestyle and environmental interventions remains the main way to reduce
      the burden of cancers. In this report, we estimate mortality from 12 types of
      cancer attributable to nine risk factors in seven World Bank regions for 2001.
      METHODS: We analysed data from the Comparative Risk Assessment project and from
      new sources to assess exposure to risk factors and relative risk by age, sex, and
      region. We applied population attributable fractions for individual and multiple
      risk factors to site-specific cancer mortality from WHO. FINDINGS: Of the 7
      million deaths from cancer worldwide in 2001, an estimated 2.43 million (35%)
      were attributable to nine potentially modifiable risk factors. Of these, 0.76
      million deaths were in high-income countries and 1.67 million in low-and-middle
      income nations. Among low-and-middle-income regions, Europe and Central Asia had
      the highest proportion (39%) of deaths from cancer attributable to the risk
      factors studied. 1.6 million of the deaths attributable to these risk factors
      were in men and 0.83 million in women. Smoking, alcohol use, and low fruit and
      vegetable intake were the leading risk factors for death from cancer worldwide
      and in low-and-middle-income countries. In high-income countries, smoking,
      alcohol use, and overweight and obesity were the most important causes of cancer.
      Sexual transmission of human papilloma virus is a leading risk factor for
      cervical cancer in women in low-and-middle-income countries. INTERPRETATION:
      Reduction of exposure to key behavioural and environmental risk factors would
      prevent a substantial proportion of deaths from cancer.

PMID- 16298216
TI  - Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective
      study.
AB  - BACKGROUND: Strokes are an important cause of morbidity and mortality in young
      adults. However, in most cases the cause of the stroke remains unclear. Anderson
      Fabry disease is an X-linked recessive lysosomal storage disease resulting from
      deficient alpha-galactosidase and causes an endothelial vasculopathy followed by
      cerebral ischaemia. To determine the importance of Fabry disease in young people
      with stroke, we measured the frequency of unrecognised Fabry disease in a cohort
      of acute stroke patients. METHODS: Between February, 2001, and December, 2004,
      721 German adults aged 18 to 55 years suffering from acute cryptogenic stroke
      were screened for Fabry disease. The plasma alpha-galactosidase activity in men
      was measured followed by sequencing of the entire alpha-GAL gene in those with
      low enzyme activity. By contrast, the entire alpha-GAL gene was genetically
      screened for mutations in women even if enzyme activity was normal. FINDINGS: 21
      of 432 (4.9%) male stroke patients and seven of 289 (2.4%) women had a
      biologically significant mutation within the alpha-GAL gene. The mean age at
      onset of symptomatic cerebrovascular disease was 38.4 years (SD 13.0) in the male
      stroke patients and 40.3 years (13.1) in the female group. The higher frequency
      of infarctions in the vertebrobasilar area correlated with more pronounced
      changes in the vertebrobasilar vessels like dolichoectatic pathology (42.9%vs
      6.8%). INTERPRETATION: We have shown a high frequency of Fabry disease in a
      cohort of patients with cryptogenic stroke, which corresponds to about 1.2% in
      young stroke patients. Fabry disease must be considered in all cases of
      unexplained stroke in young patients, especially in those with the combination of
      infarction in the vertebrobasilar artery system and proteinuria.

PMID- 16298217
TI  - Cardiovascular health after maternal placental syndromes (CHAMPS): population
      based retrospective cohort study.
AB  - BACKGROUND: Maternal placental syndromes, including the hypertensive disorders of
      pregnancy and abruption or infarction of the placenta, probably originate from
      diseased placental vessels. The syndromes arise most often in women who have
      metabolic risk factors for cardiovascular disease, including obesity, pre
      pregnancy hypertension, diabetes mellitus, and dyslipidaemia. Our aim was to
      assess the risk of premature vascular disease in women who had had a pregnancy
      affected by maternal placental syndromes. METHODS: We did a population-based
      retrospective cohort study in Ontario, Canada, of 1.03 million women who were
      free from cardiovascular disease before their first documented delivery. We
      defined the following as maternal placental syndromes: pre-eclampsia, gestational
      hypertension, placental abruption, and placental infarction. Our primary endpoint
      was a composite of cardiovascular disease, defined as hospital admission or
      revascularisation for coronary artery, cerebrovascular, or peripheral artery
      disease at least 90 days after the delivery discharge date. FINDINGS: The mean
      (SD) age of participants was 28.2 (5.5) years at the index delivery, and 75 380
      (7%) women were diagnosed with a maternal placental syndrome. The incidence of
      cardiovascular disease was 500 per million person-years in women who had had a
      maternal placental syndrome compared with 200 per million in women who had not
      (adjusted hazard ratio [HR] 2.0, 95 CI 1.7-2.2). This risk was higher in the
      combined presence of a maternal placental syndrome and poor fetal growth (3.1,
      2.2-4.5) or a maternal placental syndrome and intrauterine fetal death (4.4, 2.4
      7.9), relative to neither. INTERPRETATION: The risk of premature cardiovascular
      disease is higher after a maternal placental syndrome, especially in the presence
      of fetal compromise. Affected women should have their blood pressure and weight
      assessed about 6 months postpartum, and a healthy lifestyle should be emphasised.

PMID- 16298218
TI  - Effects of early childhood psychosocial stimulation and nutritional
      supplementation on cognition and education in growth-stunted Jamaican children:
      prospective cohort study.
AB  - Growth retardation affects about a third of children younger than age 5 years in
      developing countries and is associated with poor development. Previously, we did
      a trial of nutritional supplementation and psychosocial stimulation in stunted
      children aged 9-24 months. Non-stunted children were also assessed. Both types of
      intervention improved development. We now present the effects of early
      interventions on cognition and education in 103 of the 129 stunted children and
      compare them with 64 of the 84 non-stunted children now aged 17-18 years. We
      recorded no significant effects of nutritional supplementation. Compared with no
      intervention, stimulation resulted in higher full scale IQ scores (coefficient
      0.38, 95% CI 0.06-0.71, p=0.02) and higher scores on the verbal subscale (0.37,
      0.07-0.68, p=0.02), Peabody picture vocabulary test (7.84, 0.73-14.95, p=0.03),
      verbal analogies (0.26, 0.03-0.49, p=0.03), and reading tests (4.73, 1.31-8.14,
      p=0.007, and 2.7, 1.12-4.37, p=0.001). Overall, stunted non-stimulated
      participants had significantly poorer scores than the non-stunted group on 11 of
      12 cognitive and educational tests. Stunting in early childhood is associated
      with cognitive and educational deficits in late adolescence, which are reduced by
      stimulation at a young age.

PMID- 16298219
TI  - Gastric pneumatosis in a preterm infant.

PMID- 16298220
TI  - Periodontal diseases.
AB  - The periodontal diseases are highly prevalent and can affect up to 90% of the
      worldwide population. Gingivitis, the mildest form of periodontal disease, is
      caused by the bacterial biofilm (dental plaque) that accumulates on teeth
      adjacent to the gingiva (gums). However, gingivitis does not affect the
      underlying supporting structures of the teeth and is reversible. Periodontitis
      results in loss of connective tissue and bone support and is a major cause of
      tooth loss in adults. In addition to pathogenic microorganisms in the biofilm,
      genetic and environmental factors, especially tobacco use, contribute to the
      cause of these diseases. Genetic, dermatological, haematological, granulomatous,
      immunosuppressive, and neoplastic disorders can also have periodontal
      manifestations. Common forms of periodontal disease have been associated with
      adverse pregnancy outcomes, cardiovascular disease, stroke, pulmonary disease,
      and diabetes, but the causal relations have not been established. Prevention and
      treatment are aimed at controlling the bacterial biofilm and other risk factors,
      arresting progressive disease, and restoring lost tooth support.

PMID- 16298221
TI  - Preventing chronic diseases in China.
AB  - Chronic diseases now account for an estimated 80% of deaths and 70% of disability
      adjusted life-years lost in China. Cardiovascular diseases and cancer are the
      leading causes of both death and the burden of disease, and exposure to risk
      factors is high: more than 300 million men smoke cigarettes and 160 million
      adults are hypertensive, most of whom are not being treated. An obesity epidemic
      is imminent, with more than 20% of children aged 7-17 years in big cities now
      overweight or obese. The government of the People's Republic of China must
      confront these major challenges. The national cancer prevention and control plan
      (2004-10) is being implemented, and a national chronic disease prevention and
      control plan is due to be completed this year. Encouraging progress has been made
      in some areas, with current smoking prevalence in men declining at about 1% per
      year for a decade, and even better results in large demonstration programmes.
      Much remains to be done, and resources and sustainability are major issues.
      However, the surveillance and intervention mechanisms needed to ameliorate the
      increasing burden of chronic diseases are developing rapidly, taking account of
      the lessons learned over the past two decades.

PMID- 16298222
TI  - Risks of coronary angiography.

PMID- 16298223
TI  - Delayed motor and visual complications after attempted suicide.

PMID- 16298224
TI  - Healthcare reform involving the introduction of user fees and drug revolving
      funds: influence on health workers' behavior in southeast Nigeria.
AB  - OBJECTIVES: To assess the perceptions of health workers towards the drug
      revolving fund (DRF) scheme and the perceptions of the community members about
      health workers since the introduction of the DRF. METHODS: The study was
      conducted in four purposively selected local government areas (LGAs) in southeast
      Nigeria where the Bamako initiative DRF was operational. Data was collected using
      in-depth interviews with randomly selected health workers and exit interviews
      with patients who attended the health centers. RESULTS: There were differences
      between the ways the DRF affected health workers in the different LGAs. In
      general, the motivation of the health workers to deliver health services improved
      significantly largely because they had basic drugs to work with and they
      benefited from the drug gains accruing through the operations of the DRF.
      However, as time went on, some got de-motivated and their attentions became more
      focused on revenue generation and profit making through sale of own drugs at the
      expense of health of the people as no incentives were paid and salaries were
      delayed. Curative services were provided more than promotive and preventive
      services and drugs are prescribed irrationally. Patients showed wide spread
      dissatisfaction with fees charged, waiting time before being seen, and treatment
      instructions given to them. CONCLUSION: Governments need to focus not only on the
      provision of drugs and revenue generation but also on providing strong support
      for in-service training, monitoring and supervisory activities to improve health
      workers' attitude to work. The governments also need to explore incentives such
      as working condition and monetary incentives to motivate health workers to
      improve their performance so as to serve the consumers better.

PMID- 16298225
TI  - Deregulating the pharmacy market: the case of Iceland and Norway.
AB  - The pharmacy market in many European countries is characterised by individually
      owned pharmacies that operate under tight government control regarding barriers
      to entry, scope of activities and profit margins. Many countries are, however, in
      the process of introducing pro-competitive policies, including possibilities to
      own several pharmacies and competition based on price. In Iceland and Norway,
      restrictions to ownership and competition were relaxed in 1996 and 2001,
      respectively. In both countries, the new policies quickly led to horizontal
      integration and concentration of the market, and in Norway the merging pharmacy
      groups integrated vertically with wholesalers. By 2004, two pharmacy groups in
      Iceland and three pharmacy groups in Norway controlled 85 and 97% of the markets,
      respectively. In combination with remaining barriers to entry, this market
      concentration may call for additional pro-competitive interventions to prevent
      unfavourable developments. Such policies will simultaneously make it more
      difficult to uphold traditional social objectives related to pharmacy services.
      Experiences in both Iceland and Norway highlight the complexity of managing
      reforms that fundamentally influence competitive behaviour.

PMID- 16298226
TI  - Out-of-pocket payments and utilization of health care services in Albania:
      evidence from three districts.
AB  - Like most countries in Central and Southeastern Europe, Albania is currently
      considering a number of alternative health sector reform strategies to improve
      the availability, quality and use of primary health care services. However, in
      order to assess the likely success of such reforms, more needs to be known about
      the current levels, distribution and determinants of household out-of-pocket
      spending on health. The purpose of this paper is to use the 2002 Albania Baseline
      Health Survey, a survey of 2,000 households in Berat, Kucova, and Fier, to
      understand the magnitude and distribution of out-of-pocket payments for health
      care services and to identify the factors that operate at the household- and
      provider-levels that determine whether individuals pay for health care and how
      much is paid within the month prior to the survey. Of particular interest in the
      study is examining the extent to which households incur out-of-pocket payments
      across a number of dimensions-including health insurance status, socio-economic
      status (SES), type of service, and type of facility. The findings suggest that
      out-of-pocket payments for care provided in government facilities are widespread,
      with marked differences in payment practices between inpatient and outpatient
      care. For outpatients using Primary Health Centers (PHCs), the type of facility
      that is the focus of the government's primary health care program, average
      payments appear to be nominal (0.6% of estimated total monthly household
      expenditure per capita). The multivariate findings indicate that insurance
      coverage significantly reduces the likelihood of paying for medicines to treat
      acute and chronic health problems, but not of paying for consultations. The
      policy implications of the findings on alternative health care financing reforms
      are briefly discussed.

PMID- 16298228
TI  - Effective financing of maternal health services: a review of the literature.
AB  - Health care can be funded in a number of ways ranging from direct user charges
      (out of pocket) payments to indirect methods that pool across time (prepayment)
      and across different risk and wealth groups (insurance and general taxation). All
      these methods can be used to finance maternal health services. When assessing the
      impact of financing mechanisms it is important to be aware of the different ways
      they effect service delivery patterns and utilisation. Specifically most systems
      have both equity and efficiency aspects that combine to impact on health service
      utilisation and health status. In general indirect methods that help families to
      pool the costs of maternal health services are preferable to direct methods of
      payment. It is also clear, however, that user charges may sometimes help to
      mitigate deficiencies in systems of pooled funding. Available literature suggests
      that financing mechanisms for maternal health services could be improved by
      systems that increase transparency, help to mitigate demand-side costs of
      services and provide funding for that promote transparent charging for services.
      While the limited experience of demand-side mechanisms for improving access to
      maternal health services more evaluation is required.

PMID- 16298227
TI  - Medical decision-making for seriously ill non-elderly and elderly patients.
AB  - OBJECTIVES: Age of patients by itself is no longer a contra-indication for most
      medical interventions. The increase of possible interventions for elderly
      patients has contributed to a sharp age-specific increase of health care costs.
      Our study aimed to increase the insight in medical decision-making about life
      prolonging interventions for patients from non-elderly and elderly age groups.
      DESIGN: Case-control study. SETTING: Clinical practices in three settings:
      oncology, nursing home and cardiology. SUBJECTS: Eighty-one physicians,
      representing a response of 60%. METHODS: Face-to-face interviews using a
      structured questionnaire addressing decision-making about the application of
      taxoid treatment for breast cancer patients, the application of bypass surgery
      for patients with angina pectoris under or over 70 years of age, and referral to
      specialist treatment because of a suspected malignancy of nursing home patients
      under or over 75 years of age. RESULTS: The chance of having been treated was in
      all settings lower for patients with a relatively poor quality of life and for
      patients who had no (known) preference to be treated. No differences were found
      for chance of having been treated between non-elderly and elderly patients with
      similar patient characteristics. The only exception to this is the patient
      preference concerning treatment: elderly patients were more likely to have been
      treated against their will than non-elderly patients were. CONCLUSIONS: A
      relatively high frequency of non-treatment decisions for elderly patients may be
      predominantly explained by the fact that patient characteristics that determine
      non-treatment decision-making are more prevalent in elderly age groups, and not
      by the effect of age per se.

PMID- 16298229
TI  - Feasibility first: developing public performance indicators on patient safety and
      clinical effectiveness for Dutch hospitals.
AB  - This paper describes the development and implementation of the first national,
      public and obligatory set of hospital performance indicators in the Netherlands.
      Focusing on effectiveness and safety, the set was developed by the Dutch Health
      Care Inspectorate to improve the effectiveness and efficiency of their task:
      monitoring the quality of the care delivered by providers. In addition, the set
      would enhance the transparency of the hospital sector, and stimulate individual
      hospitals to improve their scores. Bridging some of the classic distinctions
      between 'internal' and 'external' indicators, the Inspectorate's vision was to
      rapidly produce a feasible set of indicators that would fulfill these aims, while
      maximally preventing 'side effects' such as misinterpretations, defensive or
      perverse reactions. Explicitly avoiding the trap of searching for exhaustive
      validity of the indicators, the inspectorate's motto was 'feasability first'.
      This paper describes how this simultaneously philosophical, political and
      pragmatic strategy played out successfully, and how the indicator set was
      ultimately embraced by all parties involved.

PMID- 16298230
TI  - Closing the youth access gap: the projected health benefits and cost savings of a
      national policy to raise the legal smoking age to 21 in the United States.
AB  - Current youth access laws, even if strictly enforced, do not prevent teenagers
      from obtaining cigarettes through social sources. To reduce the number of legal
      buyers a typical teenager routinely encounters, and to lessen ambiguity for
      vendors determining if a teen is of legal purchasing age, legislation raising the
      minimum legal purchase age (MLPA) for cigarettes to 21 has been discussed in
      several states. To estimate how a national law raising the smoking age to 21
      would impact smoking prevalence, net costs (in terms of compliance enforcement,
      ID checking, and medical care) and health benefits (in terms of life years and
      QALYs) to the population over time, a dynamic computer simulation model was
      developed using publicly available secondary data. The model simulations were
      carried out for several scenarios assuming varying impacts of the policy change
      on smoking initiation probability over a 50-year period. One scenario assumes
      that smoking initiation probabilities for individuals under 21 shift by 3 years
      so a 18-year old in the simulation, for example, is as likely to initiate smoking
      as an 15-year old in the status quo. Under this assumption, raising the smoking
      age would reduce smoking prevalence for adults (age 18+) from the status quo
      level of 22.1-15.4% after 50 years. Prevalence would drop from 20 to 6.6% for 14
      17-year olds, from 26.9 to 12.2% for 18-20-year olds, and from 21.8 to 15.5% for
      the 21+ group. The policy would produce a net cumulative savings to society of
      212 billion US dollars (driven by reduced medical costs), and the accumulation of
      nearly 13 million additional QALYs over the period.

PMID- 16298231
TI  - Cost-effectiveness of an active implementation strategy for the Dutch
      physiotherapy guideline for low back pain.
AB  - BACKGROUND AND PURPOSE: The treatment for patients with low back pain varies
      considerably. The Dutch Physiotherapy Association issued an evidence-based
      physiotherapy guideline for non-specific low back pain. To establish changes in
      daily practice an active implementation strategy was developed. We evaluated the
      cost-effectiveness of this implementation strategy. SUBJECTS: 113
      physiotherapists included 500 patients with low back pain. METHODS: In the
      intervention group the guideline was implemented actively, in the control group
      the standard method of dissemination was used. The patients filled in
      questionnaires at baseline and 6, 12, 26 and 52 weeks later. Direct medical
      costs, productivity costs (due to absenteeism) and quality of life (EQ-5D) were
      calculated. RESULTS: During the 1-year follow up, no differences were found in
      the quality of life, direct medical costs and productivity costs. CONCLUSION: The
      active implementation strategy appears not to be cost effective as compared to
      the standard strategy.

PMID- 16298232
TI  - Income in large residential areas and premature mortality in six countries of the
      European Union.
AB  - We study the relation between per capita income and mortality within six
      countries of the European Union - Finland, the Netherlands, Belgium, France,
      Italy and Spain - in 1981-1985 and 1996-2000. We obtained information on gross
      domestic product per capita (GDPpc) and mortality in large residential areas. The
      areas in each country were grouped in quintiles as a function of GDPpc. In 1996
      2000, a negative gradient was seen in premature mortality from all causes in men
      and women in accordance with the GDPpc quintile, except in the Netherlands and in
      women in Finland. In Belgium, France, Italy and Spain, the impact of GDPpc on
      premature mortality was stronger in 1996-2000 than in 1981-1985. All six
      countries showed a negative gradient in premature mortality from cardiovascular
      disease by GDPpc. The pathways by which residential area with lower wealth is
      associated with higher mortality are probably related with investment in economic
      and social resources over time, although for some causes of death, this
      association is not seen in some countries due to specific historic and cultural
      circumstances.

PMID- 16298233
TI  - Strategic opportunities in the oversight of the U.S. hospital accreditation
      system.
AB  - Hospital accreditation and state certification are the means that the Centers for
      Medicare & Medicaid Services (CMS) employs to meet quality of care requirements
      for medical care reimbursement. Hospitals can choose to use either a national
      accrediting agency or a state certification inspection in order to receive
      Medicare payments. Approximately, 80% of hospitals choose the Joint Commission on
      Accreditation of Healthcare Organizations (JCAHO). The purpose of this paper is
      to analyze and discuss improvements on the structure of the accreditation process
      in a Principal-Agent-Supervisor framework with a special emphasis on the
      oversight by the principal (CMS) of the supervisor (JCAHO).

PMID- 16298234
TI  - Elevated levels of neural recognition molecule L1 in the cerebrospinal fluid of
      patients with Alzheimer disease and other dementia syndromes.
AB  - In this study we surveyed a total of 218 cerebrospinal fluid (CSF) samples from
      patients with different neurological diseases including Alzheimer disease, non
      Alzheimer forms of dementia, other neurodegenerative diseases without dementia
      and normal controls to quantitate by capture ELISA the concentrations of the
      immunoglobulin superfamily adhesion molecules L1 and NCAM, and characterized by
      immunoblot analysis the molecular forms of L1 and NCAM. We found a significant
      increase of L1 and a strong tendency for increase of the soluble fragments of
      NCAM in the CSF of Alzheimer patients compared to the normal control group. The
      proteolytic fragments of L1, but not NCAM were also elevated in patients with
      vascular dementia and dementia of mixed type. Higher L1 concentrations were
      observed irrespective of age and gender. NCAM concentrations were independent of
      gender, but positively correlated with age and, surprisingly, also with incidence
      of multiple sclerosis. Thus, there was an influence of Alzheimer and non
      Alzheimer dementias and neurodegeneration on L1, whereas age and
      neurodegeneration influenced NCAM concentrations. These observations point to an
      abnormal processing and/or shedding of L1 and NCAM in dementia-related
      neurodegeneration and age, respectively, reflecting changes in adhesion molecule
      related cell interactions.

PMID- 16298236
TI  - Cerebral changes on MRI and cognitive function: the CASCADE study.
AB  - The aging, non-demented brain undergoes several physiological changes, some of
      which may affect cognitive function. The goal of the present study was to examine
      the associations between subcortical and periventricular white matter
      hyperintensities (WMHs), cortical and subcortical atrophy, and cognitive function
      (episodic memory, word fluency, attention, and perceptual, cognitive, and motor
      speed). This was done within a European collaborative study, Cardiovascular
      Determinants of Dementia (CASCADE), in which magnetic resonance imaging (MRI) was
      performed on community-dwelling individuals. The study includes 1254 persons from
      eight European study centers, ranging between 64 and 76 years of age (M 69.4+/
      3.3; 55% men). When demographics (age, education, and sex), study center, and
      concurrent brain changes had been adjusted for, periventricular WMHS predicted
      lower performance in word fluency and the Stroop test (time), and subcortical
      atrophy predicted lower performance in motor speed and the Stroop test (errors).
      The findings are consistent with findings from lesion and functional neuroimaging
      studies.

PMID- 16298235
TI  - Dissociation between CSF total tau and tau protein phosphorylated at threonine
      231 in Creutzfeldt-Jakob disease.
AB  - To study the potential diagnostic value of abnormally phosphorylated tau protein
      in Creutzfeldt-Jakob disease (CJD) compared to Alzheimer's disease (AD), we
      determined levels of tau phosphorylated at threonine 231 (p-tau231) and of total
      tau (t-tau) in cerebrospinal fluid (CSF) of CJD patients, AD patients, and
      healthy controls (HC). CJD patients showed excessively high t-tau levels but
      relatively low p-tau(231) concentrations compared to the AD group. t-tau alone
      yielded the best diagnostic accuracy to differentiate between CJD and AD
      patients, when compared to p-tau231 and the p-tau231/t-tau ratio (97, 78, and 95%
      correctly allocated cases, respectively). Our findings indicate a dissociation in
      the direction of change in CSF levels of t-tau and p-tau231 in CJD when compared
      to AD.

PMID- 16298237
TI  - Combined 99mTc-ECD SPECT and neuropsychological studies in MCI for the assessment
      of conversion to AD.
AB  - Identifying pre-clinical Alzheimer's disease (AD) in subjects with mild cognitive
      impairment (MCI) is a major issue in clinical diagnosis. Establishing a
      combination of predictive markers from different fields of research might help in
      increasing the diagnostic accuracy. Aim of this study was to evaluate the
      potential role of 99mTc-ECD single photon emission computed tomography (SPECT)
      and memory scores in predicting conversion to AD in MCI subjects. Thirty-one MCI
      subjects underwent a clinical and neuropsychological examination, and a regional
      cerebral blood flow (rCBF) SPECT scan at baseline. Subjects had been followed
      periodically through 2 years in order to monitor the progression of cognitive
      symptoms. Canonical variate analysis of principal components was able to separate
      all subjects who converted to AD from those who remained stable, the former being
      characterized by a specific hypometabolic pattern, involving the parietal and
      temporal lobes, precuneus, and posterior cingulate cortex. Canonical correlation
      analysis of combined baseline memory deficits and rCBF SPECT images identified
      pre-clinical AD with a sensitivity and specificity of 77.8%. The pattern of
      hypoperfusion 99mTc-ECD SPECT and the severity of memory deficits predict the
      risk of progression to probable AD dementia in MCI subjects.

PMID- 16298238
TI  - Medial temporal lobe neuromagnetic hypoactivation and risk for developing
      cognitive decline in elderly population: a 2-year follow-up study.
AB  - Cognition declines as a function of age. However, some elders could develop more
      severe status such as mild cognitive impairment (MCI). The aim of this study was
      the early detection of neurophysiological patterns of brain activity that may
      predict the possibility of certain subjects to develop MCI. Brain magnetic
      activity was recorded from 15 healthy subjects during a memory task by means of
      magnetoencephalography. None of the participants could be considered as MCI at
      the time of the first clinical evaluation. After 2-year follow-up, five subjects
      developed MCI and 10 maintained their cognitive status across time. The subjects
      who developed cognitive decline showed a lower number of activity sources in the
      left medial temporal lobe between 400 and 800 ms after stimulus onset, as
      compared to the non-cognitive decline group. These findings may help with the
      early identification of elderly subjects at high risk of cognitive decline,
      allowing the possibility of neuropsychological or pharmaceutical treatment that
      delay or prevent the progression of the cognitive impairment.

PMID- 16298239
TI  - Insulin effects on CSF norepinephrine and cognition in Alzheimer's disease.
AB  - We assessed the effects of induced hyperinsulinemia on plasma and cerebrospinal
      fluid (CSF) levels of norepinephrine (NE) and on cognition for patients with
      Alzheimer's disease (AD) and normal older adults. For normal adults, insulin
      increased plasma and CSF NE levels; also, recall for paraphrased details of a
      story improved as CSF NE levels increased. Mental control was positively
      correlated with CSF levels of NE for patients. These findings demonstrate that
      raising peripheral insulin levels can modulate CNS NE levels and suggest that
      insulin-stimulated increases in NE may modulate cognitive functions.

PMID- 16298240
TI  - Oxidative modification of proteins in the frontal cortex of Alzheimer's disease
      brain.
AB  - There is a large body of evidence highlighting the importance of oxidative stress
      in the pathogenesis of Alzheimer's disease (AD). We have previously standardised
      a method that can be applied to study oxidative changes in individual brain
      proteins by using two-dimensional oxyblots (Korolainen MA, Goldsteins G,
      Alafuzoff I, Koistinaho J, Pirttila T. Proteomic analysis of protein oxidation in
      Alzheimer's disease brain. Electrophoresis 2002;23(19):3428-33). Here we have
      identified proteins that exhibited oxidative changes in AD when compared to age
      matched controls and these protein changes have been further examined in relation
      to the neuropathological data. Indeed, several Tris-HCl soluble proteins tended
      to be less oxidised in AD when compared to controls. Two enzymes, mitochondrial
      glutamate dehydrogenase and cytosolic malate dehydrogenase, were increased in
      amount but showed significantly decreased degree of oxidation in AD brains when
      compared to controls. Furthermore, some changes related to the amounts or
      oxidation statuses of proteins were associated with the duration of the clinical
      impairment and also with the neuropathology. These results do not contradict the
      hypothesis of increased oxidative stress in AD but may represent co-existing
      compensatory changes in response to oxidative stress.

PMID- 16298241
TI  - Immunoproteasome and LMP2 polymorphism in aged and Alzheimer's disease brains.
AB  - In this study, we investigated the presence and role of immunoproteasome and its
      LMP2 subunit polymorphism at codon 60 in Alzheimer's disease (AD).
      Immunoproteasome was present in brain areas such as hippocampus and cerebellum
      and localized in neurons, astrocytes and endothelial cells. A higher expression
      of immunoproteasome was found in brain of AD patients than in brain of non
      demented elderly, being its expression in young brain negligible or absent.
      Furthermore, AD affected regions showed a partial decrease in proteasome trypsin
      like activity. The study of LMP2 polymorphism (R/H) showed that it does not
      influence LMP2 expression (neither the mRNA nor mature protein) in brain tissue.
      However, control brain areas of AD patients carrying the RR genotype showed an
      increased proteasome activity in comparison with RH carriers. To test whether
      this effect of the genotype might be related to AD onset we performed a genetic
      study, which allowed us to exclude an association of LMP2 codon 60 polymorphism
      with AD onset, despite its influence on the proteasome activity in human brain.

PMID- 16298242
TI  - The Arctic Alzheimer mutation facilitates early intraneuronal Abeta aggregation
      and senile plaque formation in transgenic mice.
AB  - The Arctic mutation (APP E693G) is unique, since it is located within the amyloid
      beta (Abeta) sequence and leads to Alzheimer's disease (AD). Arctic Abeta
      peptides more easily form Abeta protofibrils in vitro, but little is known about
      the pathogenic mechanism of the Arctic mutation in vivo. Here, we analyzed APP
      transgenic mice with both the Swedish and Arctic mutations (tg-APPArcSwe) and
      transgenic mice with the Swedish mutation alone (tg-APPSwe). Intense
      intraneuronal Abeta-immunoreactive staining was present in young tg-APPArcSwe
      mice, but not in tg-APPSwe mice. Intracellular Abeta aggregates in tg-APPArcSwe
      were strongly stained by antibodies recognizing the N-terminus of Abeta, while
      those recognizing the C-terminus of Abeta stained weakly. The Abeta aggregates
      inside neurons increased with age and predated extracellular Abeta deposition in
      both tg-APPArcSwe and tg-APPSwe mice. Senile plaque deposition was markedly
      accelerated in tg-APPArcSwe mice, as compared to tg-APPSwe mice. We conclude that
      the Arctic mutation causes AD by facilitating amyloidosis through early
      accumulation of intracellular Abeta aggregates in association with a rapid onset
      of senile plaque deposition.

PMID- 16298243
TI  - Inhibition of hippocampal function in mild cognitive impairment: targeting the
      cholinergic hypothesis.
AB  - Mild cognitive impairment (MCI) is a condition with an increased risk of
      developing Alzheimer's disease. Chief complaint and diagnostic criterion in
      subjects with mild cognitive impairment is memory failure. We hypothesized that
      cholinergic malfunction may underlie memory impairment in these subjects and
      applied a low dosage of an acetylcholinesterase inhibitor and modulator of
      nicotinic acetylcholine receptors, galantamine (4 mg bid), for 7 days. We used
      neuropsychological tests to investigate attention, cognitive flexibility, verbal
      and visual short-term and working memory, susceptibility to interference and
      episodic memory and functional magnetic resonance imaging to assess spatial
      navigation both prior to and after treatment. Late episodic learning and delayed
      recall improved on treatment as did recruitment of the hippocampal region during
      spatial navigation. Performance in all other neuropsychological measures remained
      unchanged. We show that an increase of cholinergic neurotransmission in subjects
      with MCI specifically improves hippocampal function and thus that a cholinergic
      deficit is functionally relevant in subjects with MCI. Malfunction of the
      cholinergic system may be tackled pharmacologically via the inhibition of
      acetylcholinesterase even when the impairment is slight.

PMID- 16298244
TI  - Transient abundance of presenilin 1 fragments/nicastrin complex associated with
      synaptogenesis during development in rat cerebellum.
AB  - Immunolocalization and expression of endogenous nicastrin (NCT) and presenilin 1
      (PS1) fragments during postnatal development of rat cerebellum were investigated
      with fragment-specific antibodies. Immunoblotting for NCT revealed the expected
      mature and immature species, which gradually declined during development. In
      contrast, the expression of PS1 N-terminal fragment exhibited a peak at postnatal
      day 14 (P14) and declined thereafter. This chronological change was similarly
      observed with PS1 C-terminal fragment. Immunoprecipitation of NCT indicated its
      physical association with PS1 fragments. Colocalization of these molecules to the
      endoplasmic reticulum in cerebellar Purkinje cells indicates that they are
      organized into a complex in developing neurons. In addition, active sites of
      synaptogenesis, the base of the external granular layer and glomeruli, contained
      PS1 fragments and smaller amount of NCT. Isolated synaptic fraction contained
      both PS1 and NCT, suggesting their functional association within synapses.
      Transient abundance of NCT and PS1 fragments as a complex, when (P14) and where
      synaptogenesis is active, is consistent with intracellular trafficking of this
      complex in developing neurons and suggests its role as gamma-secretase in
      synaptogenesis.

PMID- 16298245
TI  - Regional changes in the metabolite profile after long-term hypoxia-ischemia in
      brains of young and aged rats: a quantitative proton MRS study.
AB  - Quantitative proton magnetic resonance spectroscopy (MRS) was used to determine
      region-specific metabolic changes in young and aged animals subjected to a long
      term hypoxic-ischemic injury. Focal ischemia, which was studied as an
      experimental stroke model, was induced in 3- and 24-month-old rats by unilateral
      common carotid artery occlusion associated with 24 h of hypoxia. Eight
      metabolites were quantified from extracts in three different brain regions
      (hippocampus, frontoparietal and occipital cortices) from both the ipsilateral
      and contralateral sides. Our findings showed significant differences in lactate
      and myo-inositol concentration values in the hippocampus of the aged rats as
      compared to the same area of the young adult group under normoxic conditions.
      After hypoxia-ischemia (HI), the most relevant changes in metabolite
      concentrations were found in the hippocampal region of both young and aged groups
      as compared to their age-matched controls. Of the three brain areas under
      investigation, the hippocampus proved to be particularly susceptible to the
      prolonged hypoxia-ischemia perturbation. The effects were more evident in the
      aged animals.

PMID- 16298246
TI  - Molecular mechanism of the neurotrophic effect of GDNF on DA neurons: role of
      protein kinase CK2.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is suggested as a specific
      neurotrophic factor for midbrain dopamine (DA) neurons, but the molecular
      mechanism underlying the neuroprotective action of GDNF is not well known. In the
      present study, we have shown that GDNF increased protein kinase CK2 activity in
      rat substantia nigra (SN) in a dose-dependent and time-dependent manner. This
      effect is prevented by prior treatment of the receptor Ret blocker K-252b.
      Immunostaining results also revealed that CK2 is expressed in TH-positive neurons
      in mesencephalon culture. Transfection of the wildtype CK2alpha DNA increased,
      whereas transfection of the catalytically inactive CK2alphaA156 mutant DNA
      decreased CK2 activity in the SN. CK2alphaA156 mutant DNA also antagonized the
      enhancing effect of GDNF on CK2 activity. It also antagonized the enhancing
      effects of GDNF on tyrosine hydroxylase (TH) protein level in the SN, DA turnover
      in the striatum and rotarod performance in rats. Further, CK2alpha wildtype DNA
      increased, whereas CK2alphaA156 mutant DNA decreased TH activity in the SN
      without altering the TH protein level. On the other hand, the DA neuron toxin 1
      methyl-4-phenylpyridinium iodide (MPP+) markedly decreased the number of TH
      positive neurons and TH protein level in the SN, decreased DA level in the
      striatum and impaired rotarod performance in rats. Over-expression of the
      CK2alpha wildtype DNA partially, but significantly, prevented the deteriorating
      effect of MPP+ on these measures. Prior administration of MPP+ also antagonized
      the enhancing effect of GDNF on CK2 activity. These results together suggest that
      the CK2 signaling pathway contributes to the neuroprotective action of GDNF on DA
      neurons.

PMID- 16298247
TI  - Insulin-like growth factor 1 reduces age-related disorders induced by prenatal
      stress in female rats.
AB  - Stress during the prenatal period can induce permanent abnormalities in adult
      life such as increased anxiety-like behavior and hyperactivity of hypothalamo
      pituitary-adrenal (HPA) axis system. The present study was designed to
      investigate whether prenatal stress could induce spatial learning impairment in
      aged female rats. Furthermore, since it has been recently reported that insulin
      like growth factor 1 (IGF-1) attenuates spatial learning deficits in aged rats
      and promotes neurogenesis in the hippocampus, we assessed the impact of a chronic
      infusion of IGF-1 on age-related disorders. Our results show that females
      stressed during prenatal life exhibit learning impairments in the water maze
      task. Chronic IGF-1 treatment restores their spatial abilities, reduces their HPA
      axis dysfunction and increases plasma estradiol levels. Parallel to these
      effects, chronic IGF-1 up-regulates neural proliferation in the dentate gyrus of
      the hippocampus. These findings support the hypothesis of an early programming of
      the vulnerability to some neurological diseases during senescence and reinforce
      the potential therapeutic interest of IGF-1 during brain aging.

PMID- 16298248
TI  - Mid-life stress and cognitive deficits during early aging in rats: individual
      differences and hippocampal correlates.
AB  - We explored here the possibility that mid-life stress in rats could have
      deleterious effects on cognitive abilities during early aging, as well as the
      potential role of inter-individual differences on the development of such
      effects. Male Wistar rats were classified according to their reactivity to
      novelty (4 months old) as highly (HR) or low (LR) reactive and, at mid-life (12
      months old), either submitted to chronic stress (28 days) or left undisturbed. At
      early aging (18 months old), their learning abilities were tested in the water
      maze, and a number of neuroendocrine (plasma corticosterone; hippocampal
      corticosteroid receptors) and neurobiological (hippocampal expression of neuronal
      cell adhesion molecules) parameters were evaluated. Impaired performance was
      observed in stressed HR rats, as compared to unstressed HR and stressed LR rats.
      Increased hippocampal mineralocorticoid receptors were found in stressed LR rats
      when compared with stressed HR and control LR groups. In addition, mid-life
      stress-induced an increased corticosterone response and a reduction in NCAM-180
      isoform and L1 regardless of the behavioral trait of novelty reactivity. These
      findings highlight a role of stress experienced throughout life on cognitive
      impairment occurring during the early aging period, as well as the importance of
      taking into account individual differences to understand variability in such
      cognitive decline.

PMID- 16298249
TI  - A 20-week randomized controlled trial of estradiol replacement therapy for women
      aged 70 years and older: effect on mood, cognition and quality of life.
AB  - The results of several observational studies suggest that the use of estrogen
      replacement is associated with better mood, cognitive function and quality of
      life. Such findings are consistent with those of laboratory-based research
      showing that estrogen promotes neuronal sprouting, enhances cholinergic activity
      in the brain, decreases brain and plasma levels of beta-amyloid, increases
      serotonin postsynaptic responsivity and the turnover of noradrenaline, and
      inhibits monoamine oxidase activity. However, the findings from the Women's
      Health Initiative controlled trial showed that hormone replacement (estrogen plus
      progestin) not only failed to improve mood, cognition and quality of life but
      also increased the risk of dementia. At present, there is limited information
      about the effect of unopposed estradiol replacement therapy (ERT) on the mental
      health outcomes of women at increased risk of cognitive decline (aged 70 years
      and over). We designed the present randomized, double-blind, placebo-controlled
      trial to clarify this issue. One hundred and fifteen women were randomized to
      treatment with estradiol (n=58; 2mg per day) or placebo for a total period of 20
      weeks. The outcomes of interest in this study included changes in the Beck
      Depression Inventory (BDI) scores between baseline and week 20, as well as
      changes in quality of life scores (as measured by the SF-36) and cognitive
      function (CAMCOG, Block Design, Memory for Faces, California Verbal Learning Test
      (CVLT) and verbal fluency (VF)). Nineteen women treated with estradiol and 10 of
      those treated with placebo discontinued the use of the medication during trial,
      most frequently due to adverse reactions (OR=4.11, 95% CI=1.29-15.37). Intention
      to-treat analysis showed that the active and placebo groups did not differ in
      their response to treatment in any of the outcome measures (p>0.05). A separate
      analysis restricted to women who completed the 20-week-trial produced similar
      negative results. The results of this trial indicate that the use of a relatively
      high dosage of unopposed estrogen replacement for 20 weeks is not associated with
      significant changes in cognitive function, mood and quality of life. Other more
      efficacious and safer interventions need to be devised with the aim of improving
      the mental state and quality of life of older women.

PMID- 16298250
TI  - Longitudinal change in memory performance associated with HTR2A polymorphism.
AB  - We present a fresh approach to evaluating association with candidate genes and
      cognitive change by testing association for parameters describing individual
      growth curves from twins. Moderate genetic influences on memory in aging adults
      has been shown in quantitative genetic studies. A recently reported, association
      of a HTR2A polymorphism with episodic memory in young unrelated adults led us to
      investigate the association between a nearby polymorphism and longitudinal memory
      performance in the Swedish Adoption/Twin Study of Aging (SATSA). Analysis of
      growth curve parameters suggests that both how well individuals perform on
      figural memory at age 65 years and nonlinear change in figural memory performance
      across age are associated with HTR2A. Individuals with two copies of the common G
      allele demonstrated higher figural memory performance longitudinally than those
      with the less frequent A allele, with performance trajectories differing by 2-6%
      per year. These findings imply a role for the 5-HT2A serotonin receptor on the
      formation of episodic memories in older adults.

PMID- 16298251
TI  - Functional degradation of visual cortical cells in old cats.
AB  - Visual function declines with age. Using extracellular single-unit in vivo
      recordings, we compared the function of primary visual cortical (area 17) cells
      in young and old paralyzed, anesthetized cats. The results reveal that cortical
      neurons in old cats exhibit higher visually evoked responses, higher spontaneous
      activities, lower signal-to-noise ratios, and weaker orientation and direction
      selectivity than do cells in young adult cats. These findings are consistent with
      previously reported age related declines in cortical function in senescent
      macaque monkeys. Thus, similar declines in cortical function accompany old age in
      different mammalian species with well developed cortices.

PMID- 16298252
TI  - Hippocampal and neocortical activation during repetitive encoding in older
      persons.
AB  - Episodic memory function is known to decline in the course of normal aging;
      however, compensatory techniques can improve performance significantly in older
      persons. We investigated the effects of the memory enhancing technique of
      repetition encoding on brain activation using event-related functional magnetic
      resonance imaging (fMRI). Twelve healthy older adults without cognitive
      impairment were studied with fMRI during repetitive encoding of face-name pairs.
      During the first encoding trials of face-name pairs that were subsequently
      remembered correctly, activation of the hippocampus and multiple neocortical
      regions, including prefrontal, parietal and fusiform cortices, was observed. The
      second and third encoding trials resulted in continued activation in neocortical
      regions, but no task-related response within the hippocampus. Functional imaging
      of successful memory processes thus permits us to detect regionally specific
      responses in the aging brain. Our findings suggest that hippocampal function is
      preserved in normal aging and that repetition-based memory enhancing techniques
      may engage primarily neocortical attentional networks.

PMID- 16298253
TI  - [Glomangiomatosis].

PMID- 16298254
TI  - Classic risk factors for cardiovascular disease in chronic kidney disease.

PMID- 16298256
TI  - Sudden cardiac death and acute myocardial infarction in dialysis patients:
      perspectives of a cardiologist.
AB  - Chronic renal failure is characterized by an increased risk for cardiovascular
      morbidity and mortality, including acute myocardial infarction (AMI). AMI is
      associated with poor long-term survival in dialysis patients; the 2-year survival
      rate of 25% has remained unchanged over the past 2 decades. Although underuse of
      appropriate therapies likely contributes to adverse outcomes, recent data suggest
      that dialysis patients with AMI are more likely to have clinical presentations
      atypical for acute coronary syndrome. The risk for cardiac arrest and in-hospital
      death are increased in dialysis patients with AMI compared with a nondialysis
      cohort. The phenomenon of increased AMI mortality in patients with chronic kidney
      disease is not restricted to end-stage renal disease because there is a gradient
      of mortality risk related to decreased renal function. Sudden cardiac death is
      the single largest cause of mortality in dialysis patients. Dialysis patients are
      vulnerable to sudden cardiac death, and myocardial ischemia likely plays a major
      role. Nevertheless, after percutaneous and surgical coronary revascularization
      dialysis patients remain at high risk for sudden cardiac death, implying that
      other factors besides myocardial ischemia are important. A randomized trial
      testing the efficacy of implantable cardioverter-defibrillators for the
      prevention of sudden cardiac death in dialysis patients is warranted.

PMID- 16298255
TI  - Predictors of cardiovascular death in ESRD.
AB  - End stage renal disease (ESRD) is a situation with a cardiovascular risk profile
      of almost unique severity. While traditional risk factors dominate the scene in
      the general population, non traditional risk factors like inflammation (high C
      Reactive Protein, CRP), high brain natriuretic peptide, as an expression of left
      ventricular hypertrophy and left ventricular dysfunction, and accumulation of the
      endogenous inhibitor of the NO synthase, asymmetric dimethyl arginine are all
      markers of high CV risk of ESRD patients. To obtain a quantitative insight on the
      predictive power of traditional and emerging risk factors in ESRD, we performed a
      detailed multivariate survival analysis in the cardiovascular risk extended
      evaluation (CREED) cohort database. As expected, traditional risk factors (ie,
      age, sex, smoking, diabetes, and risk factors peculiar to the uremic state such
      as low serum albumin level) and treatment modality contributed to explain the all
      cause mortality (37%) and cardiovascular variation mortality (24%) variation as
      well. When cardiovascular comorbidities were considered in this analysis, the
      explained variation in mortality increased to 45.4% and 36.4%, respectively.
      Furthermore, a combined score based on 2 biomarkers (brain natriuretic peptide
      and C-reactive protein levels) increased the explanatory power of these models by
      about 10%. In conclusion, traditional risk factors explain about half of all
      cause and cardiovascular mortality variation in the ESRD population. The combined
      use of 2 biomarkers reflecting inflammation and left ventricular mass and
      function increases by about one fifth the explained mortality variation in this
      population. Biomarkers give information beyond that provided by traditional risk
      factors and therefore represent an useful adjunct for the definition of the risk
      profile of ESRD patients.

PMID- 16298257
TI  - Urinary albumin and cardiovascular profile in the middle-aged population.
AB  - The moderate increase in urinary albumin excretion defined as microalbuminuria is
      not rare and is associated with cardiovascular risk factors. Microalbuminuria
      prevalence is low in the absence of cardiovascular risk factors and progressively
      increases with the number cardiovascular risk factors. The main correlate of
      microalbuminuria is blood pressure, either systolic or diastolic pressure. The
      relation between blood pressure and microalbuminuria is continuous and graded
      because the microalbuminuria prevalence increases with the severity of
      hypertension. Among hypertensive patients on drug treatment, blood pressure
      control is associated with a low prevalence of microalbuminuria. Thus, blood
      pressure appears as a determinant of microalbuminuria rather than a mere
      correlate. For hypercholesterolemia, smoking, and diabetes, data are less strong
      but point to an independent positive association with microalbuminuria.
      Altogether, data indicate that microalbuminuria in the population reflects the
      presence of cardiovascular risk factors. Data on microalbuminuria and coronary
      heart disease support this idea. There is a continuous and graded relation
      between urinary albumin excretion and coronary heart disease prevalence. High
      urinary albumin excretion is likely a sign of vascular damage existing both at
      the renal and cardiac levels and induced by 1 or more uncontrolled cardiovascular
      risk factors.

PMID- 16298258
TI  - Heart disease in diabetic patients.
AB  - Cardiac artery disease and heart failure are major causes for morbidity and
      mortality in diabetes in general and in those with chronic kidney disease (CKD)
      in particular. Hypertension and dyslipidemia are more common in diabetes and the
      prevalence of coronary artery disease in diabetics is two-fold to four-fold
      higher than in nondiabetics. In those with CKD the incidence of cardiovascular
      complications is nearly two-fold higher than those without CKD. Recent studies
      suggest that the pathophysiology of cardiac disease is complex process involving
      both microvascular and macrovascular disease. In addition, myocardial
      lipotoxicity may be a novel contributing factor particularly in type 2 diabetics.
      Compelling evidence from cardiovascular outcomes trials indicates that treatment
      with drugs that block the renin-angiotensin system are cardioprotective in
      diabetics with microalbuminuria and early stages of kidney disease. Multiple risk
      factor intervention aimed at optimal blood pressure control (BP <130/<80 mmHG),
      lowering LDL cholesterol below 100 mg/dl, lowering triglyceride level to 150
      mg/dl, A1C <6.5%, treatment with an ACE inhibitor or an angiotensin II receptor
      blocker, administration of once daily low-dose aspirin and smoking cessation
      together reduce cardiovascular morbidity and mortality in type 2 diabetics. Novel
      studies including diabetics with nephropathy aimed at improving outcomes in
      diabetics by treatment of anemia and optimal control of dyslipidemia are now
      underway. These and other clinical trials should provide important new insights
      into improving the quality of life in diabetics and ultimately preventing cardiac
      disease.

PMID- 16298259
TI  - Anemia and erythropoietin in space flights.
AB  - Since the very early manned missions in space, a state of anemia associated with
      reduced erythropoietin levels and reduced plasma volume was disclosed. The
      reduction in red blood cell mass is driven by a process of selective hemolysis,
      which has been named neocytolysis. This phenomenon also occurs in people living
      at a high altitude who descend rapidly to sea level. The origin of the signal
      leading to destruction of newly produced red blood cells probably is located in
      central circulation, but the operating mechanism is unknown. The importance of
      plasma cell volume reduction in the genesis of a lower red cell mass also is
      supported by the inverse correlation seen at moderate altitude. People arriving
      at moderate altitude have increased erythropoietin concentration that decreases
      after a few days and is in inverse correlation with central venous pressure.
      Studies under simulated microgravity conditions in human beings (bed rest, head
      down tilt at -6 degrees , water immersion) and in rats provide further insight in
      unraveling the mechanism of astronauts' anemia, a problem difficult to study in
      space because of the limited availability of spaceflights.

PMID- 16298260
TI  - Erythropoietin as a volume-regulating hormone: an integrated view.
AB  - The intravascular volume consists of 40% to 45% red cells. Their production is
      controlled predominantly by erythropoietin (EPO), a hormone that is secreted
      particularly when tissue hypoxia is present. Because of this high percentage of
      the total intravascular volume the question comes to mind that, in addition to
      hypoxia, can volume-regulation mechanisms, known to be responsible for the
      maintenance of plasma volume, modulate EPO secretion when the total vascular
      volume changes? Indeed, there is evidence that in situations in which the
      intravascular volume or specifically the intrathoracic volume is altered, EPO
      secretion is affected. EPO secretion increases when the intrathoracic volume
      decreases 24 hours after water immersion or after endurance exercise when a
      negative water balance prevails. A head-down tilt on the other side induces
      central engorgement leading to a decrease of EPO concentrations. Under these
      experimental conditions no hypoxia was seen, supporting the idea that a volume
      stimulus outgoing from intrathoracic parts of the circulation modulated EPO
      secretion. Further observations from the clinical side are needed to support
      these ideas and the consequences need to be implemented into clinical practice.

PMID- 16298261
TI  - Anemia and heart failure in chronic kidney disease.
AB  - Cardiovascular disease is mainly responsible for the poor long-term survival
      observed in chronic kidney disease (CKD) patients on dialytic treatment. Anemia
      is an early complication of CKD and, by inducing important cardiovascular
      alterations, first of all left ventricular hypertrophy, it does not only impair
      quality of life, but has also been shown to be an independent risk factor for
      adverse cardiovascular outcomes in CKD patients. Clinical studies, although with
      discordant results, have shown that cardiovascular benefits, mainly in terms of
      left ventricular hypertrophy regression, may be achieved by a partial correction
      of hemoglobin levels, however, it still is unclear whether starting anemia
      correction in a very early phase of CKD or aiming for complete normalization of
      hemoglobin levels higher than the targets recommended by current guidelines may
      provide further cardiovascular advantages. Results of ongoing, large-scale,
      prospective, randomized, clinical trials therefore are awaited with much interest
      to clarify better which practices of anemia correction may provide the best
      results on the improvement of cardiovascular status and thus of long-term
      survival of patients with renal disease.

PMID- 16298262
TI  - Erythropoietin in heart failure.
AB  - The incidence of both congestive heart failure (CHF) and end-stage renal disease
      both are increasing. Anemia is common in both conditions and is associated with a
      marked increase in mortality and morbidity in both CHF and chronic kidney
      insufficiency (CKI). Each of these 3 conditions can cause or worsen the other 2.
      In other words, a vicious circle frequently is present in which CHF can cause or
      worsen both anemia and CKI, in which CKI can cause or worsen both anemia and CHF,
      and in which anemia can cause or worsen both CHF and CKI. We have called this
      vicious circle the cardio renal anemia syndrome. Optimal treatment of CHF with
      all the recommended CHF medications at their recommended doses will, in our
      experience, frequently fail to improve the CHF and CKI if anemia is present and
      is not corrected. On the other hand, correction of the anemia with subcutaneous
      erythropoietin and intravenous iron has caused a great improvement in the CHF
      including a marked improvement in patient and cardiac function and a marked
      reduction in the need for hospitalization and for high-dose diuretics. It also
      frequently has caused renal function to improve or at least stabilize. In
      addition, patients' quality of life and exercise capacity also have improved with
      the correction of the anemia. In CKI patients, anemia also may play an important
      role in increasing the risk for death, coronary heart disease, stroke, and
      progression to end-stage renal disease. Erythropoietin may have a direct positive
      effect on the heart and brain unrelated to correction of the anemia by reducing
      cell apoptosis and by increasing neovascularization, both of which could prevent
      tissue damage. This could have profound therapeutic implications not only in CHF
      but in the future treatment of myocardial infarction, coronary heart disease,
      strokes, and renal failure.

PMID- 16298263
TI  - The kidney in heart failure.
AB  - Renal dysfunction is a constant feature of congestive heart failure and is a
      stronger predictor of mortality than left ventricular ejection fraction or New
      York Heart Association classification. In heart failure, a reduction of
      glomerular filtration rate and renal plasma flow occurs, although the filtration
      fraction increases. There are many reason for this pattern. A reduction in
      effective circulating volume stimulates sympathetic activity and the renin
      angiotensin-aldosterone system, and it is associated with increased
      concentrations of atrial natriuretic peptide, brain natriuretic peptide, and
      tumor necrosis factor alpha. Because in chronic kidney disease heart dysfunction
      commonly is present, an efficient cardiologist-nephrologist interaction should be
      promoted.

PMID- 16298264
TI  - Temporary dialysis treatments for heart failure in chronic kidney disease.
AB  - Patients with cardiac disease and chronic kidney disease are admitted to our
      emergency unit with signs and symptoms of severe heart failure more and more
      frequently. Resistance to high-dose loop diuretics imposes the use of renal
      replacement therapy. We treated a group of these patients with personalized
      bicarbonate dialysis, deciding the number and frequency of treatment sessions
      according to the patient's clinical conditions. Heart failure can be classified
      as mainly diastolic or systolic. Results show that bicarbonate dialysis is
      effective and well tolerated, primarily in the treatment of patients with
      prevalently diastolic heart failure. Patients with prevalently systolic heart
      failure have a worse prognosis.

PMID- 16298265
TI  - Creatinine clearance and hemoglobin concentration before and after heart
      transplantation.
AB  - Clinical studies indicate that indices of glomerular filtration rate (GFR) as
      serum creatinine or creatinine clearance can predict the risk of death in
      congestive heart failure (CHF) and in heart transplantation. The study reports
      data on creatinine clearance before and after heart transplantation in 160
      patients followed-up for 5 years at our Unit. Pre-transplant creatinine clearance
      averaged 83.5+/-32 mL/min x 1.73 m(2) and was not significantly associated with 5
      year mortality. Creatinine clearance significantly decreased after heart
      transplantation with a linear trend up to 3 years for patients with complete
      follow-up. Data suggest that the relation between kidney function and mortality
      after heart transplantation is affected by several confounders with inclusion of
      cause of heart disease, co-morbidity, anemia, and post-transplant decrease in
      kidney function.

PMID- 16298266
TI  - Channels, carriers, and pumps in the pathogenesis of sodium-sensitive
      hypertension.
AB  - Sodium-sensitive hypertension is thought to be dependent on primary alterations
      in renal tubular sodium reabsorption. The major apical plasma membrane Na(+)
      transporters include the proximal tubular Na(+)-H(+) exchanger, the thick
      ascending limb Na(+)-K(+)-2Cl(-) cotransport system, the distal tubular Na(+)-Cl(
      ) cotransporter, and the collecting duct epithelial sodium channel (ENaC). This
      article explores the role of each transporter in the pathogenesis of
      hypertension. Although the contribution of the proximal tubule Na(+)-H(+)
      exchanger is not yet defined completely, more convincing data have been generated
      about the importance of the Na(+)-K(+)-2Cl(-). Indeed at least 2 forms of
      hypertension appear to be related to the up-regulation of the transporter: the so
      called programmed hypertension induced by low-protein diet during pregnancy and
      the early phase of hypertension in the Milan strain of rats. With respect to the
      Na(+)-Cl(-) cotransporter this may be overactive caused by inactivating mutation
      of WNK4 as in the Gordon syndrome, although it is the main actor for the
      maintenance phase of the hypertension found in the Milan strain of rats. Finally,
      the contribution of the ENaC has been established clearly; indeed, in the Liddle
      syndrome the mutation of the ENaC gene leads to a longer retention of the channel
      on the cell surface of collecting duct principal cells, thus inducing stronger
      sodium reabsorption along this segment. All these examples clearly indicate that
      renal sodium transporters may be responsible for various types of sodium
      sensitive hypertension.

PMID- 16298267
TI  - Italian audit on therapy of hypertension in chronic kidney disease: the TABLE-CKD
      study.
AB  - A large body of evidence supports the validity of decreasing blood pressure to
      target levels in patients with essential hypertension to prevent cardiovascular
      disease. This issue becomes even more critical in chronic kidney disease because
      of the remarkably greater risk for cardiovascular fatal and nonfatal events.
      Indeed, renal patients should maintain blood pressure levels less than those
      suggested for the general population. Paradoxically, management of hypertension
      in this high-risk patient population is far from optimal and certainly worse with
      respect to essential hypertension. The Target Blood Pressure Levels in Chronic
      Kidney Disease (TABLE-CKD) study, performed in Italian patients with mild to
      advanced chronic kidney disease regularly followed-up by nephrologists, has shown
      that the prevalence of patients at target blood pressure is less than 20%. The
      assessment of antihypertensive strategy in these patients, however, suggests that
      there is room for improvement; in particular, a more aggressive treatment of
      volume expansion may ameliorate hypertension control in this population
      characterized by a high salt sensitivity of blood pressure.

PMID- 16298269
TI  - Treatment of hypertension in chronic kidney disease.
AB  - Chronic kidney disease (CKD) is a major public health problem in the United
      States. It is estimated that nearly 20 million Americans have some degree of
      chronic kidney disease defined as an estimated glomerular filtration rate of less
      than sixty milliliters per minute or evidence of kidney damage by imaging study,
      biopsy, biochemical testing or urine tests with an estimated glomerular
      filtration rate more than sixty milliliters per minute. Hypertension is present
      in more than 80% of patients with CKD and contributes to progression of kidney
      disease toward end stage (ESRD) as well as to cardiovascular events such as heart
      attack and stroke. In fact the risk for cardiovascular death in this patient
      population is greater than the risk for progression to ESRD. Proteinuria is an
      important co-morbidity in hypertensives with CKD and increase risk of disease
      progression and cardiovascular events. Treatment of hypertension is therefore
      imperative. The National Kidney Foundation clinical practice guidelines recommend
      a blood pressure goal of <130 mmHg systolic and <80 mmHg diastolic for all CKD
      patients. Recent post-hoc analyses of the Modification of Diet in Renal Disease
      study indicate that lower blood pressure may provide long-term kidney protection
      in patients with nondiabetic kidney disease. Specifically a mean arterial
      pressure <92 mmHg (e.g. 120/80 mmHg) as compared to 102-107 mmHg (e.g. 140/90
      mmHg) is associated with reduced risk for ESRD. In most cases achieving this goal
      requires both non-pharmacologic and pharmacologic intervention. Dietary sodium
      restriction to no more than 2 grams daily is important. In addition, moderate
      alcohol intake, regular exercise, weight loss in those with a body mass index
      greater than 25 kg/M(2) and reduced amount of saturated fat help to reduce blood
      pressure. The first line pharmacologic intervention should be an angiotensin
      converting enzyme inhibitor or angiotensin II type 1 receptor blocker in those
      with diabetes or non-diabetics with more than 200 mg protein/gram creatinine on a
      random urine sample. For non-diabetics with less than 200 mg protein/gram
      creatinine on a random urine sample, no specific first-line drug class is
      recommended. After initial dosing with an ACEi, ARB or other drug, a diuretic
      should be added to the regimen. Thereafter, beta-blockers, calcium channel
      blockers, apha blockers and alpha 2 agonists (e.g. clonidine) and finally
      vasodilators (e.g. minoxidil) should be added to achieve blood pressure goal.
      Combinations of ACEi and ARB are helpful in reducing proteinuria and may also
      lower blood pressure further in some some cases. Blood pressure should be
      monitored closely in hypertensive patients with CKD and both clinic and home
      blood pressure measurements may help the clinician adjust treatment.

PMID- 16298268
TI  - Treatment of hypertension in Italian nephrology out-patient clinics: the THIN
      Study.
AB  - Optimal pressure control is crucial to prevent cardiovascular events in
      hypertensive patients. However, well-controlled blood pressure is encountered
      only in a small percentage of hypertensive patients managed by general
      practitioners, cardiologists, diabetologists, and hypertension specialists. This
      study aimed to evaluate the target of blood pressure obtained in Italian
      nephrology out-patient clinics. Data were collected by questionnaire sent to
      nephrology out-clinics. Questions were pertinent to patient's clinical
      characteristics, lifestyle, biochemistry, blood pressure at the first and last
      visit, and antihypertensive medications. Data pertinent to 1,632 patients were
      collected. More frequent causes of hypertension were essential hypertension
      (26%), hypertension secondary to renal insufficiency (16%), and diabetes (10%).
      At admission the systolic blood pressure was more than 140 mm Hg in 98% and
      diastolic blood pressure was more than 90 mm Hg in 95% of patients; at the last
      visit a normalized systolic and diastolic blood pressure was found in 38% and in
      75% of patients. A higher normalization rate was achieved in essential
      hypertensive patients compared with patients with hypertension secondary to
      chronic renal insufficiency and diabetes. These data indicate that improvement is
      obtained by nephrologists in controlling essential hypertension although more
      effective strategies in the management of hypertension in patients with reduced
      renal function and in diabetic patients still are required.

PMID- 16298270
TI  - Laparoscopic ovariectomy in standing cows.
AB  - The main objective of this study was to evaluate laparoscopic ovariectomy and to
      develop an optimal surgical technique for this procedure in standing cattle.
      Eight cows underwent laparoscopic ovariectomy. In two cows, a bilateral flank
      approach was used and in six cows, both ovaries were removed via a left flank
      approach. An important prerequisite for ensuring sufficient intrabdominal space
      for instrumentation, optimal endoscopic orientation and easy access to the
      ovaries and uterus was withholding feed for at least 36 h prior to surgery. The
      cows were sedated with xylazine and the portal sites infiltrated with lidocaine.
      The portal for the laparoscope was at the ventral angle of the left paralumbar
      fossa, approximately 10 cm cranioventral to the tuber coxae. The instruments were
      inserted through two portals approximately 20 cm and 30 cm ventral to the tuber
      coxae. After abdominal insufflation with carbon dioxide, the left ovary was
      grasped and local anesthetic was injected into the mesovarium and mesosalpinx.
      The mesovarium was transected using bipolar cauterization and the ovary removed
      through an extended instrument portal. The right ovary was removed in the same
      way. The incisions were closed with single interrupted absorbable sutures in the
      musculature and single interrupted non-absorbable sutures in the skin. The
      procedure lasted 120-150 min. Bilateral laparoscopic ovariectomy via left flank
      approach in standing cows is feasible. This procedure involves special
      instrumentation, but is minimally invasive and allows optimal visualization of
      the ovaries and uterus.

PMID- 16298271
TI  - Postpartum resumption of ovarian cycling activity in first-calf suckled beef cows
      exposed to familiar or unfamiliar bulls.
AB  - The objective of this experiment was to determine if the proportion of first-calf
      suckled beef cows that resumed ovulatory cycles and the interval to resumption of
      ovarian cycling activity differ after exposure to either "unfamiliar" bulls or
      cows on d 35 postpartum, after exposure to either "familiar" bulls or cows for
      the first 30-32 d after calving. Fifty AngusxHereford cows were stratified by
      calving date, calf BW, and calf sex by d 3 postpartum, and assigned to be exposed
      to familiar epididectomized bulls (BEF; n=25) or familiar mature ovariectomized
      (OVX) cows (CEF; n=25). On d 35 after calving, 12 BEF cows were assigned to be
      exposed to unfamiliar bulls (BEU); likewise, 12 CEF cows were assigned to be
      exposed to unfamiliar OVX cows (CEU). Cows were in their treatments for either 95
      d (BEF and CEF) or 60 d (BEU and CEU) during the experiment. Blood samples were
      collected every third d from the beginning to the end of the experiment. A rise
      in progesterone concentration of >0.5ng/mL in consecutive samples was used as the
      criterion for resumption of ovulatory cycles. Exposing cows to bulls on d 5 after
      calving and then switching a subset of these cows to be exposed to unfamiliar
      bulls 30-32 d later did not (P>0.10) alter: (1) the proportion of cows that
      resumed cycling activity; and (2) postpartum interval to resumption of ovarian
      cycling activity compared to cows exposed to familiar bulls. However, 32% more
      (P<0.05) cows exposed to bulls (BEF and BEU) resumed cycling activity by
      approximately 14.8 d before cows that were exposed to OVX cows (CEF and CEU). We
      conclude that the familiarity of first-calf cows to either bulls or
      ovariectomized cows, did not affect the postpartum occurrence of cycling activity
      or the interval from calving to resumption of ovulatory cycles. However, bull
      exposure, whether familiar or unfamiliar, stimulates first-calf cows to resume
      ovulatory cycles sooner after calving than if they are not exposed to bulls.

PMID- 16298272
TI  - Pregnancy diagnosis based on the fecal progesterone concentration in beef and
      dairy heifers and beef cows.
AB  - The present study was undertaken to examine whether pregnancy diagnosis was
      possible by measuring fecal progesterone concentrations in beef and dairy heifers
      and beef cows. Rectal fecal samples collected on days 18-24 after insemination or
      days 11-17 after embryo transfer were mixed with methanol and shaken for
      preparation of a fecal solution. After centrifugation, the supernatant was
      extracted with petroleum ether followed by an enzyme immunoassay for
      progesterone. All pregnant animals showed fecal progesterone concentrations
      greater than 50 ng/g of fecal material on days 18-24 after AI or estrus. In non
      pregnant animals, however, the fecal progesterone concentrations ranged widely
      from 5 to 180 ng/g of fecal material. In non-pregnant cattle, the percentage of
      cattle with <50 ng progesterone/g of fecal material compared with the total
      number was 37-60% on days 18-20, whereas the percentages increased more than 70%
      to a maximum of 78.1% on day 23. When 50 ng/g was considered as the cut-off
      value, the sensitivity and specificity of positive pregnancy tests were less than
      70% on days 21-24, and 100% for negative pregnancy tests on days 18-24. There
      were significant differences in the mean fecal progesterone concentrations
      between pregnant and non-pregnant cattle on days 19-24. These results suggest
      that feces can be utilized to substitute for plasma and milk to measure
      progesterone for the purpose of pregnancy diagnosis in heifers and cows.

PMID- 16298273
TI  - Short term effects of dexamethasone on hyaluronidase activity and sperm
      characteristics in rams.
AB  - The aim of this study was to determine the effects of dexamethasone on sperm
      characteristics and hyaluronidase activity of serum and semen. In this
      investigation, 14 healthy Akkaraman rams, at the age of 2 years and weighing
      between 50-60 kg, were used. The rams were randomly divided into two groups.
      After the last administration of dexamethasone intramuscularly at a dose of 0.25
      mg/kg, semen and blood samples were taken at different times. The results showed
      that the serum hyaluronidase activity was increased significantly (p<0.001) in
      the treatment group when compared with the control group except for the 1st hour.
      There was a significant difference (p<0.001, 0.01, 0.05) in the hyaluronidase
      activity of semen between the treatment group and the control group. Furthermore,
      there was a significant difference (p<0.01) in sperm concentration between both
      groups at all the times except the 96th hour. There were statistically
      significant (p<0.05) differences in semen volume between the treatment and
      control groups. There were also significant differences (p<0.05) in sperm
      motility between the treatment and control groups except for the 72 and 96th
      hours. These findings indicate that dexamethasone increases hyaluronidase
      activity of serum and semen, but it decreases sperm concentration, semen volume
      and sperm motility in rams. Therefore the use of these drugs in breeding rams
      during breeding season is not suitable.

PMID- 16298274
TI  - Effect of growth factors on in vitro development of caprine preantral follicle
      oocytes.
AB  - The objective of this work was to examine the effect of various growth factors
      including epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I),
      either individually or in association, in the presence of follicle stimulating
      hormone (FSH) on the in vitro growth and viability of caprine preantral follicle
      oocytes. Preantral follicles were disassociated enzymatically and mechanically
      from prepuberal caprine ovaries after the animals were anesthetically
      ovariectomized. In experiment, caprine preantral follicles in groups 1-4 were
      cultured in growth culture medium, growth culture medium+EGF, growth culture
      medium+IGF-I and growth culture medium+IGF-I+EGF, respectively, for 9 days. The
      results indicated that EGF (50 mg/l) increased the survival rate of oocytes, but
      decreased the growth rate of oocytes; IGF-I (100 mg/l) effectively maintained the
      survival of oocytes and stimulated their growth; IGF-I (100 mg/l) and EGF
      (50mg/l) in combination produced a higher effect on both of the survival and the
      growth rate of oocytes than IGF-I or EGF alone. Conclusively, the growth factors
      can effectively maintain the survival of caprine preantral follicle oocytes and
      regulated their growth in culture. EGF and IGF-I in association could
      synergically meliorate the culture system of caprine preantral follicle oocytes.

PMID- 16298275
TI  - Changes in steady-state concentrations of messenger ribonucleic acids in luteal
      tissue during prostaglandin F2alpha induced luteolysis in mares.
AB  - Transvaginal ultrasound-guided luteal biopsy was used to evaluate the effects of
      prostaglandin (PG)F2alpha on steady-state concentrations of mRNA for specific
      genes that may be involved in regression of the corpus luteum (CL). Eight days
      after ovulation (Hour 0), mares (n=8/group) were randomized into three groups:
      control (no treatment or biopsy), saline+biopsy (saline treatment at Hour 0 and
      luteal biopsy at Hour 12), or PGF2alpha+biopsy (5mg PGF2alpha at Hour 0 and
      luteal biopsy at Hour 12). The effects of biopsy on CL were compared between the
      controls (no biopsy) and saline+biopsy group. At Hour 24 (12h after biopsy) there
      was a decrease in circulating progesterone in saline group to 56% of pre-biopsy
      values, indicating an effect of biopsy on luteal function. Mean plasma
      progesterone concentrations were lower (P<0.001) at Hour 12 in the PG group
      compared to the other two groups. The relative concentrations of mRNA for
      different genes in luteal tissue at Hour 12 was quantified by real time PCR.
      Compared to saline-treated mares, treatment with PGF2alpha increased mRNA for
      cyclooxygenase-2 (Cox-2, 310%, P<0.006), but decreased mRNA for LH receptor to
      44% (P<0.05), steroidogenic acute regulatory protein to 22% (P<0.001), and
      aromatase to 43% (P<0.1) of controls. There was no difference in mRNA levels for
      PGF2alpha receptor between PG and saline-treated groups. Results indicated that
      luteal biopsy alters subsequent luteal function. However, the biopsy approach was
      effective for collecting CL tissue for demonstrating dynamic changes in steady
      state levels of mRNAs during PGF2alpha-induced luteolysis. Increased Cox-2 mRNA
      concentrations suggested that exogenous PGF2alpha induced the synthesis of
      intraluteal PGF2alpha. Thus, the findings are consistent with the concept that an
      intraluteal autocrine loop augments the luteolytic effect of uterine PGF2alpha in
      mares.

PMID- 16298276
TI  - Reproductive performance of pubertal red deer (Cervus elaphus) hinds: effects of
      genetic introgression of wapiti subspecies on pregnancy rates at 18 months of
      age.
AB  - Low reproductive productivity of young red deer (Cervus elaphus) hinds on New
      Zealand deer farms appears to reflect high incidences of puberty failure at 16
      months of age. This is despite the general attainment of average liveweights 15
      25 kg in excess of the accepted minimum threshold for puberty in subspecies of
      western European origin (scoticus, elaphus and hippelaphus) that form the basis
      of the national herd. The present study tests the hypotheses that introgression
      of the larger North American wapiti subspecies (nelsoni, manitobensis and
      roosevelti) into breeding herds (1) can be assessed from morphological features
      of individuals, (2) that there is a relationship between the level of wapiti
      parentage and non-pregnancy rate at 18 months of age (a proxy for puberty
      failure) and (3) that minimum liveweight thresholds for puberty increase with
      increasing levels of wapiti parentage. A total of 4329 18-month-old hinds across
      four "red" deer farms in southern New Zealand were scanned for pregnancy status.
      Each hind was assigned a wapiti score (WS) as a subjective assessment of the
      obviousness of wapiti features. Various body measurements were additionally
      recorded for each hind. A hair sample was collected for DNA analysis (14 markers)
      to objectively assign subspecies pedigree (i.e. "Elkmeter") on a subset of 1258
      individuals. A total of 506 (11.7%) hinds were not pregnant at 18 months of age
      with rates varying between 4.1 and 37.3% between farms and years. Mean WS
      differed significantly between farms and reflected the genetic management policy
      of each farm. WS was positively correlated to Elkmeter for each farm/year (<0.05)
      although regression slopes varied significantly. WS was able to be adjusted for
      these differences to assign a corrected WS (CWS) for all 4329 individuals that
      estimated the proportion wapiti parentage. Discriminant analysis of morphological
      variables relative to Elkmeter supported the first hypothesis and showed that
      shoulder height and body length were good indicators of the degree of wapiti
      parentage within individuals. This enabled the development of an objective
      estimate of wapiti parentage (EWP). The actual level of such parentage within
      herds ranged from <5 to >55%. There was a significant negative association
      between wapiti parentage and pregnancy, which was strongly influenced by
      liveweight, supporting the second and third hypotheses. This was manifest as
      marked displacement of pregnancy probability curves in relation to liveweight
      between genotype groups, particularly for those groups with >20% wapiti
      parentage. For example, predicted threshold liveweights required to achieve a 90%
      pregnancy rate for EWP values that represent 0, 10, 20, 30, 40 and 50% wapiti
      parentage were 81, 81, 85, 106, 127 and approximately 137 kg, respectively.
      Within the study herds, the majority of hinds of 0-20% wapiti parentage exceeded
      the predicted 90% threshold liveweights for their genotype cohort. However, hinds
      with higher levels of wapiti parentage generally fell below the predicted
      threshold for their genotype group. The data strongly suggest that under
      liveweight performance levels measured for red deer, hinds with >20% wapiti
      parentage are at high risk of puberty failure.

PMID- 16298277
TI  - Alpaca semen characteristics under free and directed mounts during a mating
      period.
AB  - Most studies in alpaca reproductive biology have been focused on female
      physiology. Only recent research is being conducted in order to increase the
      knowledge on males. Semen characteristics during breeding periods will contribute
      to understanding the poor fertility rates in alpaca. Ten adult male alpacas were
      distributed randomly into two groups and submitted alternatively to two regimens
      of semen collection of 12 days duration (day 1, initial day of semen collection).
      Semen samples were collected using an artificial vagina and a receptive, non
      pregnant female. With regimen 1, males were maintained with females except for
      the days of sexual rest (6 and 7). Semen was collected on days 1, 5, 8 and 12.
      With regimen 2, males were exposed to females for daily semen collection only,
      before and after sexual rest. Mating duration, color and volume of ejaculates,
      spermatozoa concentration and morphology were evaluated. No statistical
      differences for the variables were found between regimens that were used for
      semen collection. With respect to influence of day, however, the total numbers of
      spermatozoa ejaculated on days 1 and 5 of semen collection were statistically
      different (p<0.05). Azoospermic samples increased on days 5 and 12 of semen
      collection. Partial recovery in spermatozoa concentration and number of
      spermatozoa ejaculated were observed after sexual rest. Although normal
      spermatozoa percentage was less on day 1 (p<0.05) as compared with values found
      in the following ejaculates (days 5 and 12), the total number of normal
      spermatozoa was greater. These results support the conclusion that when male
      alpaca have a daily ejaculation during five consecutive days, they might copulate
      without having enough spermatozoa for fertilization towards the end of the mating
      period.

PMID- 16298278
TI  - Effects of extender, incubation temperature, and added seminal plasma on
      capacitation of cryopreserved, thawed boar sperm as determined by
      chlortetracycline staining.
AB  - The effect on apparent capacitation status of frozen-thawed (FT), washed boar
      sperm was examined in capacitation-supporting medium at 39 degrees C without
      added seminal plasma (SP) or supplemented with either 10 or 20% (v/v) boar SP.
      The thawed sperm from three boars were washed to remove the egg yolk-based
      freezing medium (EY) and then incubated for 1-8h after addition of SP.
      Capacitation status of the sperm was determined microscopically using
      chlortetracycline staining patterns. At 1h after the addition of 10 or 20% (v/v)
      SP, capacitated sperm decreased from 59.7 to 30.3% and from 59.5 to 26.8%,
      respectively (P<0.001). Subsequent studies examined the effect of 10% SP on
      capacitation status of FT sperm extended in either phosphate buffered saline or
      commercial thawing extender with or without prior washing of sperm to remove EY
      and incubated at 17 or 39 degrees C. No effect of SP resulted from addition to
      sperm when EY remained or when the temperature was maintained at 17 degrees C
      (P>0.1). These results indicate that SP appears able to reverse capacitation of
      FT boar sperm, but that this effect is dependent on both temperature and
      composition of the thawing extender.

PMID- 16298279
TI  - Health care disparities of children and youth: a pediatric nursing concern.

PMID- 16298282
TI  - Children's drawings as facilitators of communication: a meta-analysis.
AB  - In an attempt to explore new methods for accessing children's voices, this meta
      analysis explores the facilitative effects of offering children the opportunity
      to draw as an interview strategy as compared with a traditional directed
      interview. Based on this analysis, introducing the opportunity to draw appears to
      be a relatively robust interview strategy with a large overall effect size (d =
      .95). Both research and clinical implications are discussed.

PMID- 16298281
TI  - Adolescents' perceptions of parental roles and involvement in diabetes
      management.
AB  - This descriptive qualitative study compared how 18 teens (aged 14-16 years) with
      higher (n = 11; HiA(1c)) versus those with lower (n = 7; LoA(1c)) hemoglobin (Hb)
      A(1c) levels who met the standard of care viewed parental roles and involvement
      in diabetes management. Content analysis of the verbatim interview transcripts
      yielded five major themes. Teens in the LoA(1c) group (average HbA(1c) levels <
      or =8%) described their parents' monitoring roles more positively, whereas teens
      in the HiA(1c) group (average HbA(1c) levels >8%) were annoyed with reminders and
      described more conflict with their parents related to lack of adherence to their
      diabetes protocol. Clinicians need to assess the quality of parent-teen
      relationships and provide developmentally appropriate interventions to help teens
      and their parents effectively negotiate role transitions related to diabetes
      management during middle adolescence.

PMID- 16298283
TI  - Nursing telephone triage and its influence on parents' choice of care for febrile
      children.
AB  - Nursing telephone triage is a mechanism whereby parents call for advice and
      referrals. One common call in pediatrics concerns children's fever, which may be
      managed at home. Giving parents proper advice may avoid unnecessary visits. This
      study investigated whether home-care advice given by nurses changed parents'
      original preference for care. Data were collected using an existing database to
      determine parents' preference for location of care before and actual location of
      care after a call. Of the 110 calls, 73 parents wanted a physician or emergency
      department visit but 53 followed nursing advice for home care. Findings suggest
      that although most parents wanted to have their child seen, a majority followed
      nursing advice for home care.

PMID- 16298284
TI  - Infants who have undergone cardiac surgery: what can we learn about lengths of
      stay in the hospital and presence of complications?
AB  - The purpose of this study was to describe a population of infants undergoing
      cardiac surgery at a regional tertiary medical center and the relationship
      between age, weight, number of other diagnoses, and length of stay in the
      hospital and presence of complications. Nearly two thirds of the infants in the
      sample (n = 551; age, birth to 365 days) were younger than 28 days with a modal
      weight of 3.2 kg. There were 56 defects in the infants and 152 operative
      procedures studied. Fifty percent of the infants had one primary defect and were
      discharged in 2 to 10 days; 63.7% had no complications after surgery and were
      discharged in 4 to 15 days after surgery. Operative weight significantly
      predicted length of stay (p = .046; R(2) = .046). Operative age (p = .0011) and
      number of other diagnoses other than a child's primary defect (p = .0099)
      significantly predicted presence of fatal and nonfatal complications. As the
      number of other diagnoses increased by one, the odds of complications increased
      by 28%. As operative age increased by 1 day, the odds of complications decreased
      by 0.63%. The findings from this study can be used as evidence to support care
      that nurses give to neonates and infants undergoing cardiac surgery. These
      findings provide support for integration of this information into the informed
      consent process.

PMID- 16298285
TI  - Contributing factors to preschool unintentional injury.
AB  - Injury is the leading cause of death and disability for preschoolers in the
      United States. Young children suffer disproportionate morbidity and mortality
      when injured. Pediatric nurses modify injury risk through injury prevention
      strategies and child and family education. Effective injury prevention programs
      cannot be designed, implemented, or evaluated without a fundamental understanding
      of the factors that contribute to the phenomenon of preschool unintentional
      injury. This article includes a discussion of the factors that contribute to
      preschool unintentional injury occurrence and is based on a combination of
      epidemiology theory and the health belief model. Evidence-based suggestions for
      modification of nursing practice are provided.

PMID- 16298286
TI  - Child-to-child unintentional injury and death from firearms in the United States:
      what can be done?
AB  - Children are unintentionally killing and injuring other children at an alarming
      rate in the United States owing to the accessibility of firearms. Firearms are
      found in 33-40% of American households with children. Many of those firearms are
      stored in an unsafe manner, loaded and unlocked, leaving children vulnerable to
      injury. Health care professionals dedicated to the well-being of the pediatric
      population must take an active role in protecting our nation's children from
      unnecessary injury and death owing to the unsafe storage of firearms.

PMID- 16298287
TI  - The process of decision making about care practices for children by caregivers
      who are Taiwanese temporary residents in the United States.
AB  - People from diverse ethnic groups carry different cultural beliefs, values, and
      practices. The purpose of this study was to describe the process of decision
      making about care practices for children by caregivers who are Taiwanese
      temporary residents in the United States. Twenty-one caregivers were enrolled in
      this study. The grounded theory method was applied during data collection and
      analysis. This research revealed that physical context and environmental context
      influence the process of decision making. Five main phases of the decision-making
      process were found and described in this study.

PMID- 16298288
TI  - The impacts of the "Immune of Life" for teens module application on the coping
      behaviors and mental health of early adolescents.
AB  - This quasi-experimental research is the subsequent part of the Health Promotion
      for Early Adolescents Project, which focuses on the training of schoolteachers in
      using the module Immune of Life for Teens, which was developed in 1999, for
      evaluating its impact. The module consists of a manual and a VDO cassette display
      of a story of a teenager who has difficulty adjusting to life changes. The
      program aimed at improving the coping skills and psychological health or mental
      health of junior high school students. Schoolteachers from 13 schools
      participated nationwide as part of an experimental group and received training in
      the use of the module in their schools with students in Grades 7-9. The control
      group was composed of 3 schools that did not apply the module. Each school
      performed the pretest and posttest 1 month after the module's application. The
      total number of the students in the study was 1,580. There were 445 students in
      the control group, 474 in the experimental I group (intensive training) group,
      and 661 in the experimental II group (nonintensive group). The instruments used
      to evaluate impact were the following: (1) Young Adult Coping Orientation for
      Problem Experiences, which was developed by Patterson, McCubbin, and Grochowski
      in 1983, and the (2) Thai Mental Health Questionnaire, a 70-item self
      administered questionnaire developed by Pattrayuwat in 1999 to assess mental
      health status. The findings reveal that both experimental groups had better
      coping behaviors than the control group when using pretest scores as covariates
      (experimental I group: F = 9.425, p < .01; experimental II group: F = 22.446, p <
      .001) 1 month after the module was implemented. They also show that both
      experimental groups had better mental health than the control group when using
      pretest scores as covariates (experimental I group: F = 6.034, p < .05;
      experimental II group: F = 6.596, p < .001) 1 month after the module was
      implemented. The study confirmed the impact of the Immune of Life for Teens
      module on better coping behaviors and better mental health status among the
      subjects after it was implemented by their teachers. Thus, for further use of the
      module, intensive training for schoolteachers is recommended for the health
      promotion of early adolescents.

PMID- 16298289
TI  - Time-efficient strategies to ensure vaccine risk/benefit communication.
AB  - Vaccine risk/benefit communication is a mandatory requirement set forth by the
      National Childhood Vaccine Injury Act and is essential in enabling parents to
      make an informed decision about having their children vaccinated. This article is
      designed to improve vaccine risk/benefit communication in pediatric primary care.
      Current research related to previous efforts used to educate parents about
      vaccine safety are reviewed. Time-efficient strategies to improve vaccine
      risk/benefit communication are recommended. An example of an open communication
      letter and a list of reputable vaccine information resources are also provided.

PMID- 16298290
TI  - Atropine use in children after nerve gas exposure.

PMID- 16298291
TI  - An analysis of the concept dignity.
AB  - Dignity is a highly abstract, vague concept that is difficult to measure within
      the context of general nursing. Despite this, it is a central phenomenon to
      nursing and so it is crucial that health care workers have a clear depiction of
      dignity. This concept analysis uses the framework established by Walker and Avant
      [Walker, L.O., Avant, K.C., 1995. Strategies for Theory Construction in Nursing,
      third ed., Appleton and Lange, Connecticut] in order to heighten knowledge and
      awareness of the concept dignity. This approach also ensures that the concept is
      not being used erroneously. Respect, autonomy, empowerment and communication have
      been identified within the literature as being the defining attributes of
      dignity. Within these, further attributes are defined, which explain the complex,
      ambiguous concept that it is. This concept analysis is important for areas where
      the maintenance of dignity may be unintentionally overlooked. This can be related
      to many Emergency Departments in various parts of the world, where patients are
      awaiting beds. This is prevalent and has been slowly worsening for more than a
      decade [Derlet, R.W., Richards, J.R., 2000. Overcrowding in the Nation's
      emergency departments: complex causes and disturbing effects. Annals of Emergency
      Medicine 35 (1), 63-68; Schneider, S., Zwemer, F., Doniger, A., Dick, R.,
      Czapranski, T., Davis, E., 2001. Rochester, New York: A decade of emergency
      department overcrowding. Academic Emergency Medicine 8, 1044-1050; Nairn, S.,
      2003. The politics of beds. Accident and Emergency Nursing 11, 68-74]. Commonly
      patients are nursed in a corridor, which does not lend itself to upholding the
      dignity, privacy and confidentiality of those patients [Ball, J., Dixon, M.,
      Dolan, B., Holt, L., Wilkinson, R., 2000. Why are we waiting? Emergency Nurse 8
      (1), 173-180]. However, patients' dignity should be maintained at all times and
      health care workers need to recognise that they themselves need dignity in order
      to promote dignity in others.

PMID- 16298292
TI  - Resurrection men dig through the drug graveyard: ARYx revives problem blockbuster
      drugs.

PMID- 16298293
TI  - Design of on-target FAAH inhibitors.
AB  - In this issue of Chemistry & Biology, Alexander and Cravatt propose a model for
      the binding of carbamate inhibitors to fatty acid amide hydrolase (FAAH), the
      enzyme that breaks down signaling lipids. Using competitive activity-based
      protein profiling and click chemistry, they designed potent and selective FAAH
      inhibitors and characterized their off-target reactions.

PMID- 16298294
TI  - New light on quantum dot cytotoxicity.
AB  - As quantum dots are beginning to be used for in vivo imaging, the question of
      their long-term effect on cell viability is becoming critical. In this issue of
      Chemistry & Biology, Lovric and colleagues examine the likely role of reactive
      oxygen species in quantum dot cytotoxicity .

PMID- 16298295
TI  - Investigating beta-hydroxyenduracididine formation in the biosynthesis of the
      mannopeptimycins.
AB  - The mannopeptimycins (MPPs) are potent glycopeptide antibiotics that contain both
      D and L forms of the unique, arginine-derived amino acid beta
      hydroxyenduracididine (betahEnd). The product of the mppO gene in the MPP
      biosynthetic cluster resembles several non-heme iron, alpha-ketoglutarate
      dependent oxygenases, such as VioC and clavaminate synthase. The role of MppO in
      betahEnd biosynthesis was confirmed through inactivation of mppO, which yielded a
      strain that produced dideoxy-MPPs, indicating that mppO is essential for
      generating the beta-hydroxy functionality for both betahEnd residues.
      Characterization in vitro of recombinant His6-MppO expressed in E. coli revealed
      that MppO selectively hydroxylates the beta carbon of free L-enduracididine.

PMID- 16298296
TI  - A photoactivable probe for calcium binding proteins.
AB  - Ca2+ as a signaling molecule carries information pivotal to cell life and death
      via its reversible interaction with a specific site in a protein. Although
      numerous Ca2+-dependent activities are known, the proteins responsible for some
      of these activities remain unidentified. We synthesized and characterized a
      photoreactive reagent, azido ruthenium (AzRu), which interacts specifically with
      Ca2+ binding proteins and strongly inhibits their Ca2+-dependent activities,
      regardless of their catalytic mechanisms or functional state as purified
      proteins, embedded in the membrane or in intact cells. As expected from a Ca2+
      binding protein-specific reagent, AzRu had no effect on Ca2+-independent and Mg2+
      dependent activities. Az103Ru covalently bound, and specifically labeled, known
      Ca2+ binding proteins. AzRu is a photoreactive reagent that provides an approach
      for identification of Ca2+ binding proteins, characterization of their binding
      sites, and exploration of new Ca2+-dependent processes.

PMID- 16298298
TI  - Generation of D amino acid residues in assembly of arthrofactin by dual
      condensation/epimerization domains.
AB  - The first 6 residues of the biosurfactant lipopeptidolactone arthrofactin have
      the D configuration, yet none of the 11 modules of the nonribosomal peptide
      synthetase assembly line have epimerization domains. We show that the two-module
      ArfA subunit and the first module of the ArfB subunit, which act in tandem to
      produce the N-acyl-D-Leu1-D-Asp2-D-Thr3-S-protein intermediate, activate the L
      amino acids and epimerize them as the aminoacyl-S-pantetheinyl T domain
      intermediates before the next downstream condensation. The condensation (C)
      domains are shown to have (D)C(L) chirality in peptide bond formation. The
      upstream aminoacyl/peptidyl moiety is epimerized before condensation only when
      the condensation domains are simultaneously presented with the L-aminoacyl-S
      pantetheinyl acceptor. These (D)C(L) catalysts are dual function
      condensation/epimerization domains that can be predicted by bioinformatics
      analysis to be responsible for incorporation of all D residues in arthrofactin
      and of D residues in syringomycin, syringopeptin, and ramoplanin synthetases.

PMID- 16298299
TI  - DNA and non-DNA targets in the mechanism of action of the antitumor drug
      trabectedin.
AB  - We have analyzed the DNA binding properties of the antitumor agent trabectedin
      (ET-743, Yondelis) and different analogs, namely, ET-745, lacking the C21
      hydroxyl group, and ET-637, ET-594, ET-637-OBu, with modifications at the
      trabectedin C domain, versus their effects on cell cycle, apoptosis, and gene
      expression. ET-745 failed to bind DNA, highlighting the importance of the C21
      hydroxyl group for DNA binding. Analogs ranked trabectedin >> ET-637
      approximately ET-594 > ET-637-OBu >> ET-745 for their DNA binding capacity; ET
      637 and ET-594 display very different biological activities. Drugs were clustered
      in three major groups showing high (trabectedin, ET-637), intermediate (ET-637
      OBu), and low (ET-594, ET-745) cytotoxic activity and similar transcriptional
      profiling responses. C21-hydroxyl-deficient analogs of the above-mentioned
      compounds showed a dramatic decrease in biological activity. Our data suggest
      that trabectedin interacts with an additional non-DNA target to raise an
      effective antitumor response, and that this interaction is favored through
      trabectedin-DNA complexes.

PMID- 16298297
TI  - Mechanism of carbamate inactivation of FAAH: implications for the design of
      covalent inhibitors and in vivo functional probes for enzymes.
AB  - Fatty acid amide hydrolase (FAAH) regulates a large class of signaling lipids,
      including the endocannabinoid anandamide. Carbamate inhibitors of FAAH display
      analgesic and anxiolytic properties in rodents. However, the mechanism by which
      carbamates inhibit FAAH remains obscure. Here, we provide biochemical evidence
      that carbamates covalently modify the active site of FAAH by adopting an
      orientation opposite of that originally predicted from modeling. Based on these
      results, a series of carbamates was designed that display enhanced potency. One
      agent was converted into a "click chemistry" probe to comprehensively evaluate
      the proteome reactivity of FAAH-directed carbamates in vivo. These inhibitors
      were selective for FAAH in the nervous system, but they reacted with several
      enzymes in peripheral tissues. The experimental strategy described herein can be
      used to create in vivo probes for any enzyme susceptible to covalent inhibition.

PMID- 16298300
TI  - Inspecting the structure-activity relationship of protein kinase CK2 inhibitors
      derived from tetrabromo-benzimidazole.
AB  - CK2 is a very pleiotropic protein kinase whose high constitutive activity is
      suspected to cooperate to neoplasia. Here, the crystal structure of the complexes
      between CK2 and three selective tetrabromo-benzimidazole derivatives inhibiting
      CK2 with Ki values between 40 and 400 nM are presented. The ligands bind to the
      CK2 active site in a different way with respect to the parent compound TBB. They
      enter more deeply into the cavity, establishing halogen bonds with the backbone
      of Glu114 and Val116 in the hinge region. A detailed analysis of the interactions
      highlights a major role of the hydrophobic effect in establishing the rank of
      potency within this class of inhibitors and shows that polar interactions are
      responsible for the different orientation of the molecules in the active site.

PMID- 16298301
TI  - Ligand requirements for glmS ribozyme self-cleavage.
AB  - Natural RNA catalysts (ribozymes) perform essential reactions in biological RNA
      processing and protein synthesis, whereby catalysis is intrinsic to RNA structure
      alone or in combination with metal ion cofactors. The recently discovered glmS
      ribozyme is unique in that it functions as a glucosamine-6-phosphate (GlcN6P)
      dependent catalyst believed to enable "riboswitch" regulation of amino-sugar
      biosynthesis in certain prokaryotes. However, it is unclear whether GlcN6P
      functions as an effector or coenzyme to promote ribozyme self-cleavage. Herein,
      we demonstrate that ligand is absolutely requisite for glmS ribozyme self
      cleavage activity. Furthermore, catalysis both requires and is dependent upon the
      acid dissociation constant (pKa) of the amine functionality of GlcN6P and related
      compounds. The data demonstrate that ligand is integral to catalysis, consistent
      with a coenzyme role for GlcN6P and illustrating an expanded capacity for
      biological RNA catalysis.

PMID- 16298303
TI  - Gaucher disease-associated glucocerebrosidases show mutation-dependent chemical
      chaperoning profiles.
AB  - Gaucher disease is a lysosomal storage disorder caused by deficient
      glucocerebrosidase activity. We have previously shown that the cellular activity
      of the most common Gaucher disease-associated glucocerebrosidase variant, N370S,
      is increased when patient-derived cells are cultured with the chemical chaperone
      N-nonyl-deoxynojirimycin. Chemical chaperones stabilize proteins against
      misfolding, enabling their trafficking from the endoplasmic reticulum. Herein,
      the generality of this therapeutic strategy is evaluated with other
      glucocerebrosidase variants and with additional candidate chemical chaperones.
      Improved chemical chaperones are identified for N370S glucocerebrosidase.
      Moreover, we demonstrate that G202R, a glucocerebrosidase variant that is known
      to be retained in the endoplasmic reticulum, is also amenable to chemical
      chaperoning. The L444P variant is not chaperoned by any of the active site
      directed molecules tested, likely because this mutation destabilizes a domain
      distinct from the catalytic domain.

PMID- 16298302
TI  - Unmodified cadmium telluride quantum dots induce reactive oxygen species
      formation leading to multiple organelle damage and cell death.
AB  - Quantum dots (QDs) are luminescent nanoparticles with unique optical properties
      that have been exploited for single-cell and whole-animal imaging. When coated
      with proteins or biocompatible polymers, QDs are not deleterious to cells and
      organisms. However, when QDs are retained in cells or accumulated in the body for
      a long period of time, their coatings may be degraded, yielding "naked" QDs.
      Here, we show that "naked" QDs induce damage to the plasma membrane,
      mitochondrion, and nucleus, leading to cell death. Reactive oxygen species (ROS)
      are important players in mediating QD-induced cellular damage. QD-induced
      cytotoxicity can be reduced or even eliminated without covalent binding of
      protective agents to the QD surface. Results from these studies suggest the
      critical role of several subcellular compartments in QD-induced cytotoxicity and
      point toward multiple molecular targets in nonclassical apoptosis.

PMID- 16298304
TI  - The binding of human carbonic anhydrase II by functionalized folded polypeptide
      receptors.
AB  - Several receptors for human carbonic anhydrase II (HCAII) have been prepared by
      covalently attaching benzenesulfonamide carboxylates via aliphatic
      aminocarboxylic acid spacers of variable length to the side chain of a lysine
      residue in a designed 42 residue helix-loop-helix motif. The sulfonamide group
      binds to the active site zinc ion of human carbonic anhydrase II located in a 15
      A deep cleft. The dissociation constants of the receptor-HCAII complexes were
      found to be in the range from low micromolar to better than 20 nM, with the
      lowest affinities found for spacers with less than five methylene groups and the
      highest affinity found for the spacer with seven methylene groups. The results
      suggest that the binding is a cooperative event in which both the sulfonamide
      residue and the helix-loop-helix motif contribute to the overall affinity.

PMID- 16298305
TI  - Editorial: preschool lung function testing- the missing link.

PMID- 16298306
TI  - Inert gas washout in preschool children.
AB  - The multiple-breath inert gas washout (MBW) method is used to measure the
      efficiency of ventilation distribution in the lungs and to measure the functional
      residual capacity (FRC). It involves recordings of the concentration of an inert
      marker gas and respiratory flow at the airway opening when a subject breathes
      through a sealed facemask or a mouthpiece. The MBW method is particularly useful
      for lung function testing in preschool children (2-6 years) because it requires
      only passive cooperation and tidal breathing. The lung clearance index (LCI) is
      the cumulative expired volume required to clear an inert gas from the lungs,
      divided by the FRC. The LCI has been shown to be more sensitive than spirometry
      or airway resistance measurements in detecting lung function abnormalities in
      young children with cystic fibrosis (CF). The MBW method may be useful also for
      screening for several other disorders that affect the peripheral airways in
      children.

PMID- 16298307
TI  - Forced oscillation technique in infants and young children.
AB  - Due to its non-invasive character, the forced oscillation technique has gained
      importance in clinical research in infants and young children. Standardisation
      has enabled systematic and comparable measurements to be made in different
      laboratories throughout the world. The theoretical conditions are now fulfilled
      for use of these techniques in the clinical environment. This review discusses
      the principles, usefulness and pitfalls of various forced oscillation techniques
      in a research and clinical environment and the present and future clinical
      applications in children. It will focus particularly on the role of infant and
      preschool lung function as forced oscillation only requires minimal cooperation.

PMID- 16298308
TI  - Cold air challenge and specific airway resistance in preschool children.
AB  - Important asthma outcomes such as lung function and bronchial hyperresponsiveness
      are probably determined in early childhood. Early and longitudinal objective
      assessment of lung function and bronchial hyperresponsiveness is necessary to
      enable early diagnosis, monitor intervention and improve prognosis in preschool
      children. Cold air challenge and plethysmographic measurement of specific airway
      resistance (sRaw) are feasible candidate methods for diagnosis, clinical
      monitoring and research during this critical period of lung growth and
      development. Methodology and practical aspects of cold air challenge and
      assessment of sRaw in preschool children are reviewed. Reference values are
      provided for sRaw and have allowed discrimination between health and respiratory
      disease, both in cross-sectional and longitudinal studies. Bronchial
      hyperresponsiveness can be determined with acceptable repeatability and provides
      good discrimination between asthmatics and healthy. The effects of classic anti
      asthmatic therapies have also been documented with these techniques. The need for
      further standardisation and improvement of these methods and future perspectives
      are outlined.

PMID- 16298309
TI  - Spirometry in the pre-school age group.
AB  - Spirometry is a widely used lung-function test in school-aged children and
      adults. It can also be used to test lung function in the pre-school population,
      provided that they are tested in a child-friendly setting, by experienced
      paediatric-orientated personnel and in a way that is congruent with their
      development. Accurate results can be obtained provided care and attention are
      paid to applying quality-control criteria suitable for this age group. The
      biggest challenge is to make the testing fun.

PMID- 16298310
TI  - The measurement of airways resistance using the interrupter technique (Rint).
AB  - The interrupter technique (Rint) is a quick, easy and effort-independent way to
      obtain indirect measurements of airways resistance in the preschool child.
      Results may be obtained using a portable Rint machine or a whole-body
      plethysmograph. Normative data are available and recent studies have improved
      standardisation of the methodology. Despite this, between-occasion results can be
      variable, particularly in children with wheeze. This limits the usefulness of the
      test in the assessment of long-term interventions such as the administration of
      inhaled steroids. The most useful role for Rint, therefore, appears to be in the
      assessment of bronchodilator responsiveness where it is as sensitive as
      spirometry in separating children with reversible airways disease from healthy
      controls. This paper describes the physiology of the interrupter technique and
      the methodology needed to obtain reliable results. Normal ranges are provided.
      The clinical applicability, repeatability, strengths and limitations of the
      technique are also discussed.

PMID- 16298311
TI  - Forced oscillations, interrupter technique and body plethysmography in the
      preschool child.
AB  - The interrupter technique, forced oscillation and plethysmography have been
      increasingly used to monitor early childhood respiratory diseases over the past
      30 years. The techniques are based on different principles but generally yield
      concordant information. Data from all three techniques indicate significant
      airway response to bronchodilators in healthy and asthmatic preschool children.
      The interrupter technique is useful but yields little more than a single value of
      respiratory resistance. Forced oscillation and plethysmography may provide
      additional information relevant to the mechanisms of airway obstruction, provided
      the methodological artefacts are accounted for and corrected.

PMID- 16298312
TI  - New therapeutic agents for pulmonary vascular disease.
AB  - The improved understanding of the pathophysiology of pulmonary vascular diseases
      over the last decade has brought with it significant changes in disease
      management. Newer therapies have targeted the cardinal features of pulmonary
      hypertension, which include pulmonary vasoconstriction and vascular remodelling.
      In addition to prostacyclin, which had been the mainstay of therapy until
      recently, other available drugs include other prostacyclin analogues, endothelin
      receptor antagonists and phosphodiesterase inhibitors. This review will discuss
      some of the evidence for their use and will look towards the future in the search
      of treatments that may ultimately modify and even reverse the disease process.

PMID- 16298313
TI  - Plastic bronchitis: new insights and a classification scheme.
AB  - Plastic bronchitis is a rare disease in which there is the formation of large
      gelatinous or rigid branching airway casts. The history of the disease is
      reviewed and a classification system is proposed based on our current
      understanding. This system classifies plastic bronchitis by clinical disease
      association and cast histology. A summary of the medical literature is included
      together with guidelines for treatment. The evidence for these treatment
      decisions is reviewed.

PMID- 16298315
TI  - The evolution of diabetes diagnosis and care: a vital role for optometry.

PMID- 16298314
TI  - Food for thought.

PMID- 16298316
TI  - Retinopathy screening in individuals with type 2 diabetes: who, how, how often,
      and at what cost--an epidemiologic review.
AB  - BACKGROUND: Despite treatment regimens, which can reduce blindness, diabetic
      retinopathy remains the leading cause of irreversible blindness for persons less
      than 75 years. Screening for diabetic retinopathy in type 1 diabetes mellitus has
      proven to be both efficacious and cost effective. Although treatment has been
      shown to be equally efficacious for type 2 diabetes, the effectiveness and cost
      benefit of screening are less clear. METHODS: A systematic review of the recent
      literature on the epidemiology of retinopathy in type 2 diabetics was carried
      out. Specific issues related to the changing epidemiology of diabetes and
      diabetic retinopathy, as well as the effectiveness, and cost benefit of screening
      were evaluated. CONCLUSIONS: Diabetic retinopathy is at the convergence of
      several epidemiologic trends. Although the prevalence of diabetic retinopathy
      within the population of diagnosed diabetics may be decreasing because of
      aggressive risk factor reduction, any gains achieved are likely to be negated by
      the large increase in the prevalence of type 2 diabetes in the population owing
      to obesity. The epidemiology findings suggest that certain persons with well
      controlled type 2 diabetes may not warrant yearly examination for diabetic
      retinopathy; however, given the low percentage of diabetics who are currently
      screened for retinopathy, it would seem unwise to recommend changes in the timing
      of examination. Evidence appears to suggest that photoscreening is a viable
      alternative to a screening examination.

PMID- 16298317
TI  - The effect of laser refractive surgery on the on-field performance of
      professional baseball players.
AB  - BACKGROUND: The aim of this study was to determine the effect of laser refractive
      surgery on the offensive performance of professional baseball players. METHODS:
      Extensive search of the public media was conducted to determine which major
      league baseball players had undergone laser refractive surgery and when the
      procedure was performed. Baseball performance data were then used to determine
      presurgery and postsurgery baseball performance averages. A total of 17 position
      players were identified; however, 5 of these players were not considered in the
      analysis owing to insufficient playing experience either before or after the
      laser procedure. RESULTS: No statistically significant or practically significant
      difference was found between the presurgery and postsurgery means on either on
      base percentage (P = 0.31), batting average (P = 0.39), slugging percentage (P =
      0.66) or on-base plus slugging (OPS; P = 0.997) of major league baseball players.
      CONCLUSIONS: These preliminary findings suggest that professional baseball
      players should not expect a laser refractive surgical procedure to significantly
      improve their offensive baseball performance, despite the elimination of glasses
      or contact lens wear.

PMID- 16298318
TI  - Blood pressure control in an African American sample with diabetes mellitus in an
      urban eye clinic.
AB  - BACKGROUND: The adequate control of blood pressure in patients with diabetes
      mellitus (DM) is important to limit the ocular and systemic complications of the
      disease. Hypertension in African Americans is among the highest in the world.
      This cross-sectional study reports the level of blood pressure control in a small
      sample of African American patients with DM at an urban eye care facility using
      the criteria defined by the Joint National Committee on Prevention, Detection,
      Evaluation and Treatment of High Blood Pressure (JNC VII). METHODS: Five
      attending faculty members of the Illinois College of Optometry identified 234
      African American patients with a diagnosis of DM over a period of 16 months.
      Blood pressure readings were recorded once at the time of their visit and were
      classified as controlled or uncontrolled based on the JNC VII cutoff of blood
      pressure less than 130/80 mmHg. RESULTS: Among the 234 African American patients
      in this study, 174 (74.4%) reported having DM and hypertension, and 60 (25.6%)
      reported having DM without hypertension. Of the patients with DM and a self
      reported diagnosis of hypertension, 13.2% were controlled. Of the patients with
      diabetes without a self-reported diagnosis of hypertension, 26.7% were found to
      be adequately controlled. For the pooled data of 234 patients with diabetes,
      16.7% met the JNC VII guidelines. CONCLUSION: The inadequate control of blood
      pressure in the African American population with DM is associated with increased
      disability and death from cardiovascular and renal disease. The results of this
      small cross-sectional study are consistent with those of other studies that show
      poor control of blood pressure in African American patients who have DM.
      Preventable blindness secondary to accelerated diabetic retinopathy from
      uncontrolled hypertension is a concern to all eye care practitioners.

PMID- 16298319
TI  - Optometry within hospitals at the Veterans Administration.
AB  - BACKGROUND: This study was designed to determine the use of optometrists with the
      Veterans Health Administration hospital system and to develop accurate statistics
      regarding the number and type of services these doctors provide. The findings
      help describe their responsibilities in the treatment and management of ocular
      diseases and their use of diagnostic and therapeutic drugs. The study also
      investigated what, if any, role optometrists play beyond care in the education
      and research practices of the hospital. METHODS: A descriptive analysis was
      conducted through the use of surveys and interviews of department chiefs or
      medical directors. A survey was sent out to 149 Veterans Affairs (VA) Hospitals,
      located using the VA facility locator Web site. Data were tabulated, aggregated,
      and analyzed. RESULTS: A response rate of 81% was achieved (122 surveys
      returned), 98% of which (120 facilities) provide eye services to their patients
      in either an outpatient or inpatient capacity. One hundred seventeen (98%) of
      these had optometrists affiliated with their facility. These optometrists were
      responsible for providing a range of services, prescribing the use of diagnostic
      or therapeutic drugs, and participating in educational training of other health
      personnel. CONCLUSION: Optometry has developed a strong partnership with the
      Veterans Health Administration, and act as an integral part of its hospital
      services. The VA has developed a workforce mix that should serve as a model for
      managed care organizations.

PMID- 16298320
TI  - Five rules to evaluate the optic disc and retinal nerve fiber layer for glaucoma.
AB  - A systematic approach for the examination of the optic disc and retinal nerve
      fiber layer is described that will aid in the detection of glaucoma. This
      approach encompasses 5 rules: evaluation of optic disc size, neuroretinal rim
      size and shape, retinal nerve fiber layer, presence of parapapillary atrophy, and
      presence of retinal or optic disc hemorrhages. A systematic process enhances the
      ability to detect glaucomatous damage as well as the detection of progression,
      and facilitates appropriate management.

PMID- 16298321
TI  - Significant enhancement of fluorescence on hybridization of a molecular beacon to
      a target DNA in the presence of a site-specific DNA nickase.
AB  - We have developed a simple isothermal (55 degrees C) reaction that permits
      detection of DNA targets using only two components: a molecular beacon and a site
      specific DNA nickase without deoxyribonucleotide triphosphates and primers. The
      loop sequence of the molecular beacon should contain a DNA nickase recognition
      site. The nickase-molecular beacon (NMB) combination permits a 100-fold increase
      in fluorescent signal. The applications of the NMB assay for enhancement of
      fluorescent signal in some isothermal methods are discussed.

PMID- 16298322
TI  - Lifetime fluorescence method for determining membrane topology of proteins.
AB  - Recently, we introduced a sensitive method for determining the bilayer topology
      (cis- or trans-leaflet location) of single-site cysteine-linked 7-nitrobenz-2-oxa
      1,3-diazol-4-yl (NBD) fluorescent labels on membrane proteins. It uses a novel
      quencher, LysoUB, composed of a single acyl chain attached to a UniBlue
      chromophore. In its original version, the method relied on the comparison of
      steady-state fluorescence measurements of membrane-inserted proteins in samples
      with different distributions of the LysoUB in cis- and trans-leaflets of the
      lipid bilayer. Here we modify the method to take advantage of the fluorescence
      lifetime methodology, which allows us to simplify sample manipulation and, as a
      result, increase the reliability of topology determination. We tested the method
      using three model systems with artificially created all-cis, all-trans, and
      isotropic distribution of NBD. Because the quenching efficiency is higher when
      LysoUB and NBD are in the same leaflet, introduction of the quencher into the cis
      leaflet results in a predictably different amount of quenching for these three
      model systems. Indeed, the addition of 2% LysoUB into the all-cis NBD model
      system causes strong reduction of the longest lifetime (from 8.1 to 4.9 ns),
      whereas the same addition of LysoUB results in marginal quenching (from 8.7 to
      8.5 ns) in the case of all-trans NBD. This difference provides a good basis for
      topology determination using time-resolved fluorescence quenching.

PMID- 16298323
TI  - Development of surface-based assays for transmembrane proteins: selective
      immobilization of functional CCR5, a G protein-coupled receptor.
AB  - A general method to develop surface-based assays for transmembrane (TM) receptor
      function(s) without the need to isolate, purify, and reconstitute the proteins is
      presented. Based on the formation of an active surface that selectively
      immobilizes membrane vesicles, the method is illustrated using the chemokine
      receptor CCR5, a member of the largest family of cell surface eukaryotic TM
      proteins, the G protein-coupled receptors (GPCRs). The method begins with a
      protein-resistant surface containing a low percentage (1-5%) of surface-bound
      biotin on gold as the initial template. Surface plasmon resonance (SPR) data show
      specific immobilization of functional CCR5 after the initial template is
      activated by immobilization of rho 1D4 antibody, an anti-rhodopsin monoclonal
      antibody specific for the carboxyl terminal nine amino acids on bovine rhodopsin
      that had been engineered into the carboxyl terminus of CCR5, and exposure to
      vesicles obtained from mammalian cells transfected with a synthetic human CCR5
      gene. Activation of the initial template is effected by sequential immobilization
      of avidin, which binds to the biotin in the initial template, a biotinylated goat
      anti-mouse immunoglobulin G (Bt-IgG), which binds to the avidin binding sites
      distal to the surface and the F(c) portion of the rho 1D4 antibody through its
      F(ab) region(s) and finally rho 1D4. This approach establishes a broad outline
      for the development and application of various assays for CCR5 functions. SPR
      data also showed that vesicle immobilization could be achieved through an
      integrin-integrin antibody interaction after activation of the initial template
      with a goat anti-human integrin beta1 antibody. These results suggest that the
      generic nature of the initial platform and flexibility of the subsequent surface
      activation for specific immobilization of membrane vesicles can be applied to the
      development of assays for other GPCRs or TM receptors for which antibodies are
      available or can be engineered to contain a particular antibody epitope.

PMID- 16298324
TI  - Resonance light scattering profiles must be corrected for instrument performance.

PMID- 16298325
TI  - Imaging membrane processes in erythrocyte ghosts by surface fusion of a chromatic
      polymer.

PMID- 16298326
TI  - Prolidase deficiency and the biochemical assays used in its diagnosis.

PMID- 16298327
TI  - Effective novel dissociation methods for intact protein: heat-assisted nozzle
      skimmer collisionally induced dissociation and infrared multiphoton dissociation
      using a Fourier transform ion cyclotron resonance mass spectrometer equipped with
      a micrometal electrospray ionization emitter.
AB  - Heating of a nano-electrospray ionization (nanoESI) source can improve the
      dissociation efficiency of collisionally induced dissociation (CID) methods, such
      as nozzle-skimmer CID (NS-CID) and infrared multiphoton dissociation (IRMPD), for
      large biomolecule fragmentation. A metal nanoESI emitter was used due to its
      resistance to heating above 250 degrees C. This novel method for the dissociation
      of large biomolecular ions is termed "heat-assisted NS-CID" (HANS-CID) or "heat
      assisted IRMPD" (HA-IRMPD). Multiple charged nonreduced protein ions (8.6 Da
      ubiquitin, 14 kDa lysozyme, and 67 kDa bovine serum albumin) were directly
      dissociated by HANS-CID and HA-IRMPD to effectively yield fragment ions that
      could be assigned. The fragment ions of ubiquitin by HANS-CID can be analyzed by
      tandem mass spectrometry (MS/MS) using sustained off-resonance irradiation CID
      (SORI-CID) and IRMPD. In addition, a native large protein, immunoglobulin G (IgG,
      150 kDa), was efficiently dissociated by HA-IRMPD. The product ions that were
      obtained reflected the domain structure of IgG. However, these product ions of
      IgG and lysozyme were not dissociated by MS/MS using the same heating energetic
      methods such as IRMPD and SORI-CID.

PMID- 16298328
TI  - Adenovirus type 5 intrinsic adsorption rates measured by surface plasmon
      resonance.
AB  - Intrinsic adsorption rates of whole adenovirus type 5 (Ad5) onto a
      diethylaminoethyl (DEAE) anion exchange surface are measured for the first time
      by surface plasmon resonance (SPR). Fitting SPR sensorgrams to a two-compartment
      mass transport reaction model distinguishes intrinsic adsorption rates from slow
      diffusive Ad5 mass transport. Ad5 is a widely used viral vector for gene therapy
      that binds electrostatically to surfaces of cells and synthetics such as
      membranes, chromatographic resins, and glass. Increasing NaCl concentration from
      4.8 to 14.4mM shifts binding of whole Ad5 from diffusion control to a regime
      where both sorption and diffusion affect binding. Intrinsic adsorption rates for
      Ad5-DEAE interaction are 16 times faster than intrinsic adsorption rates for Ad5
      fiber knob interacting with soluble extracellular domain of coxsackievirus
      adenovirus receptors (s-CAR).

PMID- 16298330
TI  - Determination of molybdenum and/or ruthenium in urine using electrospray
      ionization mass spectrometry.

PMID- 16298329
TI  - Infrared spectroscopy used to evaluate glycosylation of proteins.
AB  - Infrared (IR) spectroscopy is used for studying the carbohydrate moieties of
      glycosylated proteins. IR spectra of mono- and disaccharides in the fingerprint
      region are specific to each sugar and to the environment of the sugar molecules
      (i.e., aqueous solution or anhydrous glass phase). The IR spectra of glycosylated
      proteins (mucin, soybean peroxidase, collagen IV, and avidin) were compared with
      those of the constituent sugars and cytochrome c (a protein with no
      glycosylation). Our results demonstrate that the IR absorption spectra of
      glycosylated proteins show distinct absorption bands for the sugar moiety, the
      protein amide group, and water. Therefore, IR can be used to detect
      glycosylation.

PMID- 16298331
TI  - Study of the interaction of sulfur dioxide derivative with cardiac sodium
      channel.
AB  - The effects of sulfur dioxide (SO(2)) derivatives (bisulfite and sulfite, 1:3
      M/M) on voltage-dependent sodium channel in isolated rat ventricular myocyte were
      studied using the whole cell patch-clamp technique. SO(2) derivatives increased
      sodium current (I(Na)) in a concentration-dependent manner. SO(2) derivatives at
      10 microM significantly shifted steady-state inactivation curve of I(Na) to more
      positive potentials, but did not affect the activation curve. SO(2) derivatives
      markedly shifted the curve of time-dependent recovery of I(Na) from inactivation
      to the left, and accelerated the recovery of I(Na). SO(2) derivatives also
      significantly shortened the activation and inactivation time constants of I(Na).
      These results indicated that SO(2) derivatives produced concentration-dependent
      stimulation of cardiac sodium channels, which due mainly to the interaction of
      the drug with sodium channels in the inactivated state.

PMID- 16298332
TI  - In vivo and in vitro comparison of the effects of FGF-2 null and haplo
      insufficiency on bone formation in mice.
AB  - We previously reported that deletion of the Fgf2 gene (Fgf2-/-) resulted in
      decreased bone mass in adult mice. This study examines the effect of haplo
      insuffiency (Fgf2+/-) on bone loss in vertebrae from these mutant mice. Fgf2+/+
      mice attained peak bone mass at 8-9 months of age. In contrast BMD was
      significantly reduced in vertebrae from adult (8-9) Fgf2+/- mice. Exogenous FGF-2
      rescued reduced bone nodule formation in Fgf2+/- and Fgf2-/- cultures. Runx2 mRNA
      was reduced in cultures from Fgf2+/- and Fgf2-/- mice. FGF receptor2 mRNA and
      protein were markedly reduced in Fgf2+/- and Fgf2-/- mice. Decreased bone
      formation in Fgf2 mutant mice may correlate with impaired FGFR signaling,
      decreased Runx2 gene expression.

PMID- 16298333
TI  - Doxorubicin prevents endoplasmic reticulum stress-induced apoptosis.
AB  - Several cellular stress signaling pathways initiate apoptosis in eukaryotic
      cells, but the interactions and coordination between the pathways have not been
      elucidated. In this study, apoptosis was triggered in MCF7 human breast carcinoma
      cells using doxorubicin, a topoisomerase inhibitor, and an endoplasmic reticulum
      (ER) stress inducer, thapsigargin, the latter causing the unfolded protein
      response (UPR). Interestingly, compared to treatment with doxorubicin or
      thapsigargin alone, cell death was reduced by treatment with both stress
      inducers. In contrast to another topoisomerase inhibitor, etoposide, doxorubicin
      markedly decreased apoptosis induced by thapsigargin; this doxorubicin effect was
      accompanied by reduced expression of the UPR-specific proapoptotic protein, C/EBP
      homologous protein, and its upstream transcription factor, ATF4. We further found
      that doxorubicin downregulates the expression of ATF4 mRNA, indicating that
      doxorubicin interferes with the UPR at the level of ATF4 transcription. Taken
      together, the data suggest that ER stress-initiated cell death might be regulated
      by doxorubicin.

PMID- 16298334
TI  - Role of Per1-interacting protein of the suprachiasmatic nucleus in NGF mediated
      neuronal survival.
AB  - We previously identified Per1-interacting protein of the suprachiasmatic nucleus
      (PIPS) in rats. To reveal its role, its tissue distribution was examined by
      immunoblotting. PIPS-like immunoreactive substance (PIPSLS) was observed in the
      brain, adrenal gland, and PC12 cells. Since PIPS, which has no nuclear
      localization signal (NLS), is translocated into nuclei of COS-7 cells in the
      presence of mPer1, the effect of NGF on nuclear localization of PIPS was examined
      using PC12 cells. NGF caused nuclear translocation of either PIPSLS or GFP-PIPS.
      NGF mediated nuclear translocation of PIPSLS was blocked by K252a, a TrkA
      inhibitor, or wortmannin, a PI3K-inhibitor. Gab1, which is implicated in TrkA
      signaling and has NLS, co-immunoprecipitated with PIPSLS from PC12 cells using an
      anti-PIPS antibody. Inhibition of PIPS expression by RNAi increased levels of
      apoptosis in PC12 cells. These findings suggest that nuclear translocation of
      PIPS is involved in NGF mediated neuronal survival via TrkA, PI3K, and Gab1
      signaling pathway.

PMID- 16298336
TI  - BnNHL18A shows a localization change by stress-inducing chemical treatments.
AB  - The two genes, named BnNHL18A and BnNHL18B, showing sequence homology with
      Arabidopsis NDR1/HIN1-like (NHL) genes, were isolated from cDNA library prepared
      with oilseed rape (Brassica napus) seedlings treated with NaCl. The transcript
      level of BnNHL18A was increased by sodium chloride, ethephon, hydrogen peroxide,
      methyl jasmonate, or salicylic acid treatment. The coding regions of BnNHL18A and
      BnNHL18B contain a sarcolipin (SLN)-like sequence. Analysis of the localization
      of smGFP fusion proteins showed that BnNHL18A is mainly localized to endoplasmic
      reticulum (ER). This result suggests that the SLN-like sequence plays a role in
      retaining proteins in ER membrane in plants. In response to NaCl, hydrogen
      peroxide, ethephon, and salicylic acid treatments, the protein localization of
      BnNHL18A was changed. Our findings suggest a common function of BnNHL18A in
      biotic and abiotic stresses, and demonstrate the presence of the shared mechanism
      of protein translocalization between the responses to plant pathogen and to
      osmotic stress.

PMID- 16298335
TI  - Vaspin gene expression in human adipose tissue: association with obesity and type
      2 diabetes.
AB  - Recently, vaspin was identified as an adipokine with insulin-sensitizing effects,
      which is predominantly secreted from visceral adipose tissue in a rat model of
      type 2 diabetes. In this study, we examined whether vaspin mRNA expression is a
      marker of visceral obesity and correlates with anthropometric and metabolic
      parameters in paired samples of visceral and subcutaneous adipose tissue from 196
      subjects with a wide range of obesity, body fat distribution, insulin
      sensitivity, and glucose tolerance. Vaspin mRNA expression was only detectable in
      23% of the visceral and in 15% of the subcutaneous (SC) adipose tissue samples.
      Vaspin mRNA expression was not detectable in lean subjects (BMI<25) and was more
      frequently detected in patients with type 2 diabetes. No significant correlations
      were found between visceral vaspin gene expression and visceral fat area or SC
      vaspin expression. However, visceral vaspin expression significantly correlates
      with BMI, % body fat, and 2 h OGTT plasma glucose. Subcutaneous vaspin mRNA
      expression is significantly correlated with WHR, fasting plasma insulin
      concentration, and glucose infusion rate during steady state of an euglycemic
      hyperinsulinemic clamp. Multivariate linear regression analysis revealed % body
      fat as strongest predictor of visceral vaspin and insulin sensitivity as
      strongest determinant of SC vaspin mRNA expression. In conclusion, our data
      indicate that induction of human vaspin mRNA expression in adipose tissue is
      regulated in a fat depot-specific manner and could be associated with parameters
      of obesity, insulin resistance, and glucose metabolism.

PMID- 16298337
TI  - RshA mimetic peptides inhibiting the transcription driven by a Mycobacterium
      tuberculosis sigma factor SigH.
AB  - SigH, an alternative sigma factor in Mycobacterium tuberculosis, is a central
      regulator in responses to the oxidative and heat stress. This SigH activity is
      specifically controlled by an anti-sigma factor RshA during expression of stress
      related genes. Thus, the specific interaction (k(on)=1.15x10(5) (M(-1) s(-1)),
      k(off)=1.7x10(-3) (s(-1)), KD=15 nM, determined in this study) between SigH and
      RshA is crucial for the survival and pathogenesis of M. tuberculosis. Using phage
      display peptide library, we defined three specific regions on RshA responsible
      for SigH binding. Three RshA mimetic peptides (DAHADHD, AEVWTLL, and CTPETRE)
      specifically inhibited the transcription initiated by SigH in vitro. One of them
      (DAHADHD) diminished the extent of binding of RshA to SigH in a dose-dependent
      manner. The binding affinity (KD) of this peptide to SigH was about 1.2 microM.
      These findings might provide some insights into the development of new peptide
      based drugs for TB.

PMID- 16298339
TI  - NAD(P)H oxidase-derived reactive oxygen species regulate angiotensin-II induced
      adventitial fibroblast phenotypic differentiation.
AB  - Phenotypic differentiation of adventitial fibroblasts into myofibroblasts is an
      essential feature of vascular remodeling. The present study was undertaken to
      test the hypothesis that reactive oxygen species (ROS) are involved in rat
      adventitial fibroblast differentiation to myofibroblast. Activation of alpha
      smooth muscle actin (alpha-SMA) was used as a marker of myofibroblast.
      Angiotensin II increased intracellular ROS in adventitial fibroblasts that was
      completely inhibited by the free radical scavenger NAC, the NAD(P)H oxidase
      inhibitor DPI, and transfection of antisense gp91phox oligonucleotides.
      Myofibroblast differentiation was prevented by inhibition of ROS generation with
      DPI, NAC, and antisense gp91phox as shown by decreased expression of alpha-SMA.
      Angiotensin II rapidly induced phosphorylation of p38 MAPK and JNK, both of which
      were inhibited by DPI, NAC, antisense gp91phox, and the selective AT1 receptor
      antagonist, losartan. Inhibiting p38MAPK with SB202190 or JNK with SP600125 also
      reduced angiotensin II-induced alpha-SMA expression. These findings demonstrate
      that angiotensin II induces adventitial fibroblast differentiation to
      myofibroblast via a pathway that involves NADPH oxidase generation of ROS and
      activation of p38MAPK and JNK pathways.

PMID- 16298338
TI  - Capacity of human beta-defensin expression in gene-transduced and cytokine
      induced cells.
AB  - The purpose of this study was to determine the capacity of cells transduced with
      human beta-defensins (HBDs) to express antimicrobial peptides, since sufficient
      expression level is required for effective antimicrobial activity. Retroviral
      vector pBabeNeo and lentiviral vector SIN18cPPTRhMLV (SIN18) carrying HBDs were
      utilized to transduce non-HBD-expressing cells such as fibroblasts or HBD
      producing oral epithelial cells. We found that HBD-3 gene transfer to fibroblasts
      was possible not via retrovirus but by direct vector transfection. SIN18 had high
      transduction efficiencies (80.9-99.9%) and transduced cells expressed higher
      amounts of HBD-2 than those by pBabeNeo. Primary human gingival epithelial cells
      (HGECs) expressed greater amounts of HBD-2 than primary fibroblasts after
      lentiviral transduction. Additionally, HBD-2 secretion from transduced HGECs
      cells was further increased when stimulated with IL-1 or TNFalpha. Our data
      indicate that while HBD-2 expression is limited in primary fibroblasts, its
      expression in HGECs may be maximized by gene transduction plus cytokine
      induction.

PMID- 16298340
TI  - Characterization of a human SWI2/SNF2 like protein hINO80: demonstration of
      catalytic and DNA binding activity.
AB  - The proteins belonging to SWI2/SNF2 family of DNA dependent ATPases are important
      members of the chromatin remodeling complexes that are implicated in epigenetic
      control of gene expression. We have identified a human gene with a putative DNA
      binding domain, which belongs to the INO80 subfamily of SWI2/SNF2 proteins. Here
      we report the cloning, expression, and functional activity of the domains from
      hINO80 gene both in terms of the DNA dependent ATPase as well as DNA binding
      activity. A differential expression of the various domains within this gene is
      detected in human tissues while a ubiquitous expression is detected in mice. The
      intranuclear localization is demonstrated using antibodies directed against the
      DBINO domain of hINO80.

PMID- 16298341
TI  - Generation of a rabbit V(H) domain antibody polyspecific to c-Met and adenoviral
      knob protein.
AB  - Several types of bispecific antibodies with affinity to both adenoviral coat
      proteins and a targeted antigen have been developed with the aim of providing the
      specific delivery of adenoviral gene therapy vehicle. From a phage display
      library of combinatorial dAb2s (each with an anti-adenoviral knob protein V(H)
      fragment linked with an anti-c-Met V(H)), we serendipitously enriched and
      isolated a clone, JS5, that has polyspecificity such that it binds both the
      adenoviral knob protein and c-Met, despite having only one V(H) domain. Our
      indirect observations suggest that the polyspecificity of JS5 is developed
      through accumulation of antibody specificity. The method of sequential
      immunization of a rabbit, first with the adenoviral knob protein and then with
      target antigens, may provide a method by which monoclonal antibodies with stand
      alone polyspecificity may be developed. Such targeted polyspecific antibodies
      could readily be used for re-directing adenoviral vectors to target cells.

PMID- 16298342
TI  - Smad3 mediates TGF-beta1-induced collagen gel contraction by human lung
      fibroblasts.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a key mediator in tissue repair
      and fibrosis. Using small interference RNA (siRNA), the role of Smad2 and Smad3
      in TGF-beta stimulation of human lung fibroblast contraction of collagenous
      matrix and induction of alpha-SMA and the role of alpha-SMA in contraction were
      assessed. HFL-1 cells were transfected with Smad2, Smad3 or control-siRNA, and
      cultured in floating Type I collagen gels +/- -TGF-beta1. TGF-beta1 augmented gel
      contraction in Smad2-siRNA- and control-siRNA-treated cells, but had no effect in
      Smad3-siRNA-treated cells. Similarly, TGF-beta1 upregulated alpha-SMA in Smad2
      siRNA- and control-siRNA-treated cells, but had no effect on Smad3-siRNA-treated
      cells. Alpha-SMA-siRNA-treated cells did not contact the collagen gels with or
      without TGF-beta1, suggesting alpha-SMA is required for gel contraction. Thus,
      Smad3 mediates TGF-beta1-induced contraction and alpha-SMA induction in human
      lung fibroblasts. Smad3, therefore, could be a target for blocking contraction of
      human fibrotic tissue induced by TGF-beta1.

PMID- 16298343
TI  - Histone deacetylase 3 represses p15(INK4b) and p21(WAF1/cip1) transcription by
      interacting with Sp1.
AB  - Histone deacetylase 3 (HDAC3) has been implicated to play roles in governing cell
      proliferation. Here we demonstrated that the overexpression of HDAC3 repressed
      transcription of p15(INK4b) and p21(WAF1/cip1) genes in 293T cells, and that the
      recruitment of HDAC3 to the promoter regions of these genes was critical to this
      repression. We also showed that HDAC3 repressed GAL4-Sp1 transcriptional
      activity, and that Sp1 was co-immunoprecipitated with FLAG-tagged HDAC3. We
      conclude that HDAC3 can repress p15(INK4b) and p21(WAF1/cip1) transcription by
      interacting with Sp1. Furthermore, knockdown of HDAC3 by RNAi up-regulated the
      transcriptional expression of p15(INK4b), but not that of p21(WAF1/cip1),
      implicating the different roles of HDAC3 in repression of p15(INK4b) and
      p21(WAF1/cip1) transcription. Data from this study indicate that the inhibition
      of p15(INK4b) and p21(WAF1/cip1) may be one of the mechanisms by which HDAC3
      participates in cell cycle regulation and oncogenesis.

PMID- 16298344
TI  - Structural and biochemical characterization of DSL ribozyme.
AB  - We recently reported on the molecular design and synthesis of a new RNA ligase
      ribozyme (DSL), whose active site was selected from a sequence library consisting
      of 30 random nucleotides set on a defined 3D structure of a designed RNA
      scaffold. In this study, we report on the structural and biochemical analyses of
      DSL. Structural analysis indicates that the active site, which consists of the
      selected sequence, attaches to the folded scaffold as designed. To see whether
      DSL resembles known ribozymes, a biochemical assay was performed. Metal-dependent
      kinetic studies suggest that the ligase requires Mg2+ ions. The replacement of
      Mg2+ with Co(NH3)6(3+) prohibits the reaction, indicating that DSL requires
      innersphere coordination of Mg2+ for a ligation reaction. The results show that
      DSL has requirements similar to those of previously reported catalytic RNAs.

PMID- 16298345
TI  - Molecular cloning and radioligand binding characterization of the chemokine
      receptor CCR5 from rhesus macaque and human.
AB  - The aim of this study was to determine if macaque represents a suitable species
      for the pre-clinical evaluation of novel CCR5 antagonists, such as maraviroc (UK
      427,857). To do this we cloned and expressed CCR5 from rhesus macaque and
      compared the binding properties of [125I]-MIP-1beta and [3H]-maraviroc with human
      recombinant CCR5. [125I]-MIP-1beta bound with similar high affinity to CCR5 from
      macaque (K(d) = 0.24 +/- 0.05 nM) and human (K(d) = 0.23 +/- 0.05 nM) and with
      similar kinetic properties. In competition binding studies the affinity of a
      range of human chemokines for macaque CCR5 was also similar to human CCR5.
      Maraviroc inhibited binding of [125I]-MIP-1beta to CCR5 from macaque and human
      with similar potency (IC50 = 17.50 +/- 1.24 nM and 7.18 +/- 0.93 nM,
      respectively) and antagonised MIP-1beta induced intracellular calcium release
      mediated through CCR5 from macaque and human with similar potency (IC50 = 17.50
      +/- 3.30 nM and 12.07 +/- 1.89, respectively). [3H]-maraviroc bound with high
      affinity to CCR5 from macaque (K(d) = 1.36+/-0.07 nM) and human (K(d) = 0.86 +/-
      0.08 nM), but was found to dissociate approximately 10-fold more quickly from
      macaque CCR5. However, as with the human receptor, maraviroc was shown to be a
      high affinity, potent functional antagonist of macaque CCR5 thereby indicating
      that the macaque should be a suitable species in which to evaluate the
      pharmacology, safety and potential mechanism-related toxicology of novel CCR5
      antagonists.

PMID- 16298347
TI  - Targeting the forgotten transglycosylases.
AB  - Forty years ago, moenomycin was reported as a representative of a novel natural
      product class with strong antibacterial activity against Gram-positive organisms.
      Moenomycin was developed as an antimicrobial growth promoter in animal feeds.
      Mechanistically, moenomycin acts via inhibition of the transglycosylation process
      at the final stage of the peptidoglycan biosynthesis, in particular through
      binding directly to the transglycosylase enzymes, thereby preventing
      polymerisation of lipid II into linear peptidoglycan. Despite moenomycin's
      success, no developments of direct transglycosylase enzyme inhibitors were
      reported for over 30 years, probably due to the complexities and uncertainties
      surrounding the transglycosylation process, in particular the number of enzymes
      involved in the process and their specific roles. The development of better
      research tools and an improved understanding of the transglycosylation process,
      together with the increasing threat presented by multidrug-resistant bacteria,
      have led to a resurfacing of interest in targeting the forgotten
      transglycosylases. In addition, several new generation glycopeptides in clinical
      development inhibit the transglycosylation process, adding further value to the
      approach. In this paper, we summarise some of the developments in the area of
      transglycosylase inhibitors over the last 10 years.

PMID- 16298346
TI  - Cell cycle arrest and proapoptotic effects of the anticancer cyclodepsipeptide
      serratamolide (AT514) are independent of p53 status in breast cancer cells.
AB  - In a search for new anticancer agents, we have identified serratamolide (AT514),
      a cyclodepsipeptide from Serratia marcescens 2170 that induces cell cycle arrest
      and apoptosis in various cancer cell lines. A cell viability assay showed that
      the concentrations that cause 50% inhibition (IC50) in human cancer cell lines
      range from 5.6 to 11.5 microM depending on the cell line. Flow cytometry analysis
      revealed that AT514 caused cell cycle arrest in G0/G1 or cell death, depending on
      the cell type and the length of time for which the cells were exposed to the
      drug. Subsequent studies revealed that AT514-induced cell death is caused by
      apoptosis, as indicated by caspases activation (8, 9, 2 and 3) and cleavage of
      poly (ADP-ribose) polymerase (PARP), release of cytochrome c and apoptosis
      inducing factor (AIF) from mitochondria, and the appearance of apoptotic bodies
      and DNA laddering. Alterations in protein levels of Bcl-2 family members might be
      involved in the mitochondrial disruption observed. AT514 induced p53 accumulation
      in wild-type p53 cells but cell death was observed in both deficient and wild
      type p53 cells. Our results indicate that AT514 induces cell cycle arrest and
      apoptosis in breast cancer cells irrespectively of p53 status, suggesting that it
      might represent a potential new chemotherapeutic agent.

PMID- 16298348
TI  - Arylpiperazines displaying preferential potency against chloroquine-resistant
      strains of the malaria parasite Plasmodium falciparum.
AB  - Arylpiperazines in which the terminal secondary amino group is unsubstituted were
      found to display a mefloquine-type antimalarial behavior in being significantly
      more potent against the chloroquine-resistant (W2 and FCR3) strains of Plasmodium
      falciparum than against the chloroquine-sensitive (D10 and NF54) strains.
      Substitution of the aforementioned amino group led to a dramatic drop in activity
      across all strains as well as abolition of the preferential potency against
      resistant strains that was observed for the unsubstituted counterparts. The data
      suggest that unsubstituted arylpiperazines are not well-recognized by the
      chloroquine resistance mechanism and may imply that they act mechanistically
      differently from chloroquine. On the other hand, 4-aminoquinoline-based
      heteroarylpiperazines in which the terminal secondary amino group is also
      unsubstituted, were found to be equally active against the chloroquine-resistant
      and chloroquine-sensitive strains, suggesting that chloroquine cross-resistance
      is not observed with these two 4-aminoquinolines. In contrast, two 4
      aminoquinoline-based heteroarylpiperazines are positively recognized by the
      chloroquine resistance mechanism. These studies provide structural features that
      determine the antimalarial activity of arylpiperazines for further development,
      particularly against chloroquine-resistant strains.

PMID- 16298350
TI  - Exercise affects glutamate receptors in postsynaptic densities from cortical mice
      brain.
AB  - Physical activity has been proposed as a behavior intervention that promotes
      mental health and some of the benefits induced by exercise have been related to
      the glutamatergic system. Indeed, glutamate is the most abundant excitatory
      neurotransmitter in brain. Thus, we evaluated if voluntary exercise in mice could
      modulate glutamatergic synapses at level of postsynaptic density (PSD). Through
      Western blot, we found that exercise during 1 month increased glutamatergic
      related protein content in PSD from cortex of mice. Exercise increased the
      immunocontent of GluR1 (129%), SAP-97 (179%), GRIP-1 (129%), and in less extent,
      GluR2/3 (118%) and PSD-95 (112%) proteins. The overall content of NMDA subunits
      R1, R2A and R2B were not altered in mice that had exercised, however, the
      phosphorylated NMDA subunits, phospho-NMDAR1 (150%), and phospho-NMDAR2B (183%)
      showed a strong increase. Because exercise increased the content of
      phosphorylated forms of NMDA receptors, we evaluated the binding of MK-801, a
      specific ligand that binds to open NMDA channel. Exercise increased the binding
      of MK-801 in cortical cellular membranes in 51%. Altogether, our results point to
      a modulation of glutamatergic synapses by exercise with likely implications in
      the exercise-induced mental health.

PMID- 16298349
TI  - The effect of low estrogen state on serotonin transporter function in mouse
      hippocampus: a behavioral and electrochemical study.
AB  - Defects in serotonergic transmission, including serotonin transporter (SERT)
      function, have been implicated in depression, anxiety disorders and some aspects
      of schizophrenia. The sex steroid hormone estrogen is known to modulate
      functional SERT activity, but whether it is up- or down-regulated is unclear. The
      aim of the present study was to examine the effect of a low estrogen state in
      mice on the behavioral effect of drugs acting through the SERT, serotonin uptake
      kinetics and SERT density in the hippocampus. We compared control mice,
      ovariectomized (OVX) C57BL/6J mice and aromatase knockout (ArKO) mice that are
      unable to produce estrogen. Fluoxetine treatment, but not fenfluramine treatment,
      significantly increased prepulse inhibition (PPI), a measure of sensorimotor
      gating, in C57BL/6J mice. The effect of fluoxetine was greater in OVX compared to
      sham-operated mice. In ArKO and J129 wild-type mice, fluoxetine increased PPI to
      the same extent while fenfluramine increased PPI more in ArKO mice compared to
      controls. Measurement of the time-course for diffusion and reuptake of exogenous
      serotonin in the CA3 region of the hippocampus showed that, in OVX mice, the
      fluoxetine-induced slowing of signal decay after application of serotonin was
      enhanced when compared to sham-operated controls. Similarly, in ArKO mice, the
      effect of fluoxetine was enhanced, suggesting that SERT function was greater than
      in J129 wild-type controls. Measurement of SERT density by [3H]-citalopram
      autoradiography, revealed an 18% decrease in hippocampus of OVX mice compared to
      intact controls. SERT density was also significantly reduced in nucleus accumbens
      (26%) but not in other regions, such as the raphe nuclei. Together, these results
      suggest that a low estrogen state increases SERT activity in the hippocampus
      despite an apparent reduction in SERT density. The behavioral consequences of
      these changes depend on the model of estrogen state used.

PMID- 16298351
TI  - Chemical sympathectomy attenuates myenteric but not dorsal vagal complex Fos-like
      immunoreactivity induced by cholecystokinin-8 in the rat.
AB  - Vagotomy and capsaicin treatment attenuate dorsal vagal complex (DVC) but not
      myenteric Fos-like immunoreactivity (Fos-LI) induced by cholecystokinin-8 (CCK
      8). The goal of this experiment is to test the role of the sympathetic nervous
      system in the pathway by which CCK-8 increases myenteric Fos-LI. Adult male
      Sprague-Dawley rats were pretreated with guanethidine sulfate (40 mg/kg daily for
      5 weeks) or vehicle intraperitoneally (IP), and injected with CCK-8 (40
      microg/kg) or saline IP. Fos-LI was then quantified in the DVC and the myenteric
      neurons of the duodenum and jejunum using a diaminobenzidine reaction.
      Guanethidine pretreatment attenuated myenteric but not DVC Fos-LI induced by CCK
      8. These findings demonstrate that sympathetic neurons play a role in mediating
      the myenteric Fos-LI response to CCK. They also suggest differential mediation of
      myenteric and DVC responses to CCK.

PMID- 16298352
TI  - Correlation between quantitative imaging and behavior in unilaterally 6-OHDA
      lesioned rats.
AB  - We evaluated correlation between neurochemical and functional alterations of the
      nigrostriatal dopaminergic system in rat brains lesioned with 6-hydroxydopamine
      (6-OHDA), that model hemi-Parkinson's disease (PD), by using three different
      quantitative in vivo and in vitro methods. Rats unilaterally lesioned with
      different doses of 6-OHDA underwent two types of in vivo experiments: (1) a
      rotational behavioral study with methamphetamine (MAP) or apomorphine (APO); and
      (2) a positron emission tomography (PET) study with [11C]PE2I (radioligand for
      dopamine transporters) or [11C]raclopride (radioligand for dopamine D2
      receptors). An in vitro autoradiographic study with the same radioligands was
      also conducted. The number of rotations after the MAP or APO injection increased
      with increased doses of 6-OHDA. The in vitro and in vivo binding of [11C]PE2I
      dose-dependently decreased in response to the 6-OHDA injections, while that of
      [11C]raclopride dose-dependently increased. There was a significant negative
      hyperbolic correlation between the number of rotations after MAP injection and
      the binding of [11C]PE2I. In contrast, there was a significant positive linear
      correlation between the number of rotations after APO injections and the binding
      of [11C]raclopride. These results robustly reveal a molecular pharmacological
      basis of parkinsonian symptoms in animal models of PD, and indicate the utility
      and validity of in vivo PET measurements in assessing pre- and post-synaptic
      dopaminergic functions.

PMID- 16298353
TI  - Monitoring cholinesterases to detect pesticide exposure.
AB  - Progress toward a standard blood cholinesterase assay to assess pesticide
      exposures in the agricultural workplace and to identify possible victims of
      chemical warfare agents is discussed. Examples given are drawn from
      collaborations with clinical laboratories in California and the Department of
      Defense Cholinesterase Reference Laboratory (CRL).

PMID- 16298354
TI  - Inherited disorders of neurotransmitters in children and adults.
AB  - Inherited disorders of neurotransmitters are a group of neurometabolic syndromes
      attributable to a primary disturbance of neurotransmitter metabolism or
      transport. This is an enlarging group of recognized disorders requiring
      specialized diagnostic procedures for detection. This review considers clinical
      disorders of biopterin, catecholamines, serotonin, glycine, pyridoxine, and GABA
      metabolism. Newly described syndromes such as cerebral folate deficiency and
      pyridoxal-5-phosphate dependency are included. The disorders of the metabolic
      pathways of biopterin, catecholamines, and serotonin are linked due to their
      common synthetic components. Glycine encephalopathy represents an enlarging
      phenotype related to abnormalities of the glycine degradative cleavage system.
      Both pyridoxine and pyridoxal-5-phosphate dependency need to be considered in
      refractory neonatal seizures. The most common disorder of GABA metabolism is
      SSADH deficiency, which has a broad phenotype of mental retardation, epilepsy,
      ataxia, and hyporeflexia and which invokes the combined problems of elevated
      brain GABA and GHB.

PMID- 16298355
TI  - Improved prediction of early-onset coronary artery disease using APOE epsilon4,
      BChE-K, PPARgamma2 Pro12 and ENOS T-786C in a polygenic model.
AB  - OBJECTIVES: Coronary artery disease (CAD) is often polygenic due to multiple
      mutations that contribute small effects to susceptibility. Since most prior
      studies only evaluated the contribution of single candidate genes, we therefore
      looked at a combination of genes in predicting early-onset CAD [apolipoprotein E
      (APOE) epsilon4, butyrylcholinesterase (BChE) K, peroxisome proliferator
      activated receptor gamma2 (PPARgamma2) Pro12Ala and endothelial nitric oxide
      synthase (ENOS) T-786C]. DESIGN AND METHODS: We examined the frequencies,
      individually and in combination, of all four alleles among patients with early
      onset CAD (n = 150; <50 years), late-onset CAD (n = 150; >65 years) and healthy
      controls (n = 150, age range 47-93 years). Differences in the proportion of
      subjects in each group with the given gene combination were assessed and
      likelihood ratios (LR) were calculated using logistic regression to combine the
      results of multiple genes. RESULTS: Early-onset CAD patients had increased, but
      non-significant, frequencies of PPARgamma2 Pro12/Pro12 (P = 0.39) and ENOS T-786C
      (P = 0.72), while BChE-K was only significantly higher in early-onset CAD
      patients compared to controls (P = 0.03). There were significantly more APOE
      epsilon4 alleles alone (P = 0.02) or in combination with BChE-K (P = 0.02) among
      early-onset CAD patients compared to late-onset CAD ones or controls. When
      combined, there was a higher prevalence of all four alleles in early-onset CAD
      (early-onset CAD patients: 10.7%, late-onset CAD patients: 3.3% and controls:
      2.7%, P = 0.01). LR for early-onset CAD for a single allele was relatively small
      (1.08 for PPARgamma2 to 1.70 for APOE epsilon4). This increased to 2.78 (1.44
      5.37) when combining all four alleles, therefore increasing the pre-test
      probability of CAD from 5% to a post-test probability of 12.7%. CONCLUSIONS:
      While any single mutation causes only a mildly increased LR (none > 1.7), in
      combination, the likelihood of early-onset CAD increased to 2.78 with four
      mutations. The genetics of early-onset CAD appear to be multifactorial, requiring
      polygenic models to elucidate risk.

PMID- 16298356
TI  - Determination of free and protein-bound methadone and its major metabolite EDDP:
      enantiomeric separation and quantitation by LC/MS/MS.
AB  - OBJECTIVE: To measure free and protein-bound R- and S-enantiomers of methadone
      and its major metabolite, 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine
      (EDDP) in serum. METHODS: To determine free fraction, samples were filtered using
      ultrafiltration membranes with a molecular weight cut-off of 10,000 Da and
      extracted using liquid-liquid extraction. The solvent extract was evaporated and
      reconstituted in mobile phase for analysis by LC/MS/MS. Total analyte was
      determined by extracting unfiltered samples. Enantiomeric separation was by
      chiral chromatography. RESULTS: LC conditions resulted in baseline separation of
      R- and S-EDDP, and 85% resolution of methadone enantiomers. Precision of spiked
      specimens for both R- and S-methadone and R- and S-EDDP was less than 10% at 100
      nM, and did not exceed 20% at 10 nM. CONCLUSIONS: Using minimal sample clean-up
      and a total instrument run-time of 10 min, a rapid, sensitive and highly specific
      method was developed for quantitation of free and total R- and S-enantiomers of
      methadone and EDDP.

PMID- 16298357
TI  - Advances in classification of EEG signals via evolving fuzzy classifiers and
      dependant multiple HMMs.
AB  - Two novel approaches to the problem of brain signals (electroencephalogram (EEG))
      classification are introduced in the paper. The first method is based on a
      modular probabilistic network architecture that employs multiple dependant hidden
      Markov models (DM-HMM-D) on the input features (channels). The second method,
      eClass, is based on an on-line evolvable fuzzy rule base of EEG signal prototypes
      that represent each class and take into consideration the spatial proximity
      between input signals. Both approaches use supervised learning but differ in
      their mode of operation. eClass is designed recursively, on-line, and has an
      evolvable structure, while DM-HMM-D is trained off-line, in a block-based mode,
      and has a fixed architecture. Both methods have been extensively tested on real
      EEG data that is recorded during several experimental sessions involving a single
      female subject who is exposed to mild pain induced by a laser beam. Experimental
      results illustrate the viability of the proposed approaches and their potential
      in solving similar classification problems.

PMID- 16298358
TI  - Osteoblast viability and differentiation with Me2SO as cryoprotectant compared to
      osteoblasts from fresh human iliac cancellous bone.
AB  - The aim of this study was to compare the viability of human osteoblasts
      cryopreserved with Me2SO to that of fresh human iliac cancellous bone using cell
      culture techniques. Osteoblasts were obtained by spontaneous outgrowth of human
      iliac cancellous bone specimens in experiment I. In experiment II, human iliac
      cancellous bone was frozen with 10% Me2SO at -80 degrees C for 2 weeks and
      osteoblasts grew spontaneously after thawing at 37 degrees C by removing Me2SO
      with sucrose. The cells were grown in culture flasks containing DMEM as a culture
      medium, supplemented with 10% fetal calf serum. They were kept at 37 degrees C in
      a humidified atmosphere of 95% air and 5% CO2. Cells from the second passage were
      plated at a density of 5 times 10(3) cells/cm2 in 24-well plates. For detection
      of viability and differentiation, WST-1 assay, determination of alkaline
      phosphatase activity, concentration of procollagen I peptide, concentration of
      osteocalcin, and indirect immunofluorescence for osteopontin, collagen type I,
      integrin beta1, and fibronectin were applied. Experiments were conducted at four
      stages of confluence (days 4, 7, 14, and 21 after plating the cells). Based on
      the results of this study, we conclude that osteoblast-like cells survived
      cryopreservation and synthesized a range of markers that were consistent with
      this cell type.

PMID- 16298359
TI  - Meta-analysis for deriving age- and gender-specific dose-response relationships
      between urinary cadmium concentration and beta2-microglobulinuria under
      environmental exposure.
AB  - A meta-analysis was conducted to derive age- and gender-specific dose-response
      relationships between urinary cadmium (Cd) concentration and beta2
      microglobulinuria (beta2MG-uria) under environmental exposure. beta2MG-uria was
      defined by a cutoff point of 1000 microg beta2-microglobulin/g creatinine. We
      proposed a model for describing the relationships among the interindividual
      variabilities in urinary Cd concentration, the ratio of Cd concentrations in the
      target organ and in urine, and the threshold Cd concentration in the target
      organ. The parameters in the model were determined so that good agreement might
      be achieved between the prevalence rates of beta2MG-uria reported in the
      literature and those estimated by the model. In this analysis, only the data from
      the literature on populations environmentally exposed to Cd were used. Using the
      model and estimated parameters, the prevalence rate of beta2MG-uria can be
      estimated for an age- and gender-specific subpopulation for which the
      distribution of urinary Cd concentrations is known. The maximum permissible level
      of urinary Cd concentration was defined as the maximum geometric mean of the
      urinary Cd concentration in an age- and gender-specific subpopulation that would
      not result in a statistically significant increase in the prevalence rate of
      beta2MG-uria. This was estimated to be approximately 3 microg/g creatinine for a
      population in a small geographical area and approximately 2 microg/g creatinine
      for a nationwide population.

PMID- 16298360
TI  - Hydroxyl-radical-dependent DNA damage by ambient particulate matter from
      contrasting sampling locations.
AB  - Exposure to ambient particulate matter (PM) has been reported to be associated
      with increased respiratory, cardiovascular, and malignant lung disease.
      Previously we have shown that PM can induce oxidative DNA damage in A549 human
      lung epithelial cells. The aims of the present study were to investigate the
      variability of the DNA-damaging properties of PM sampled at different locations
      and times and to relate the observed effects to the hydroxyl-radical (OH)
      generating activities of these samples. Weekly samples of coarse (10-2.5 microm)
      and fine (<2.5 microm) PM from four sites (Nordrheim Westfalen, Germany) were
      analyzed for hydrogen-peroxide-dependent OH formation using electron paramagnetic
      resonance and formation of 8-hydroxydeoxyguanosine (8-OHdG) in calf thymus DNA
      using an immuno-dot-blot assay. DNA strand breakage by fine PM in A549 human lung
      epithelial cells was quantified using the alkaline comet assay. Both PM size
      distribution fractions elicited OH generation and 8-OHdG formations in calf
      thymus DNA. Significantly higher OH generation was observed for PM sampled at
      urban/industrial locations and for coarse PM. Samples of fine PM also caused DNA
      strand breakage in A549 cells and this damage could be prevented using the
      hydroxyl-radical scavengers 5,5-dimethyl-1-pyrroline-N-oxide and dimethyl
      sulfoxide. The observed DNA strand breakage appeared to correlate with the
      hydroxyl-radical-generating capacities of the PM samples but with different
      profiles for rural versus urban/industrial samples. In conclusion, when
      considered at equal mass, OH formation of PM shows considerable variability with
      regard to the sampling location and time and is correlated with its ability to
      cause DNA damage.

PMID- 16298361
TI  - Glucocorticoid interaction with aggression in non-mammalian vertebrates:
      reciprocal action.
AB  - Socially aggressive interaction is stressful, and as such, glucocorticoids are
      typically secreted during aggressive interaction in a variety of vertebrates,
      which may both potentiate and inhibit aggression. The behavioral relationship
      between corticosterone and/or cortisol in non-mammalian (as well as mammalian)
      vertebrates is dependent on timing, magnitude, context, and coordination of
      physiological and behavioral responses. Chronically elevated plasma
      glucocorticoids reliably inhibit aggressive behavior, consistent with an
      evolutionarily adaptive behavioral strategy among subordinate and submissive
      individuals. Acute elevation of plasma glucocorticoids may either promote an
      actively aggressive response via action in specialized local regions of the brain
      such as the anterior hypothalamus, or is permissive to escalated aggression
      and/or activity. Although the permissive effect of glucocorticoids on aggression
      does not suggest an active role for the hormone, the corticosteroids may be
      necessary for full expression of aggressive behavior, as in the lizard Anolis
      carolinensis. These effects suggest that short-term stress may generally be best
      counteracted by an actively aggressive response, at least for socially dominant
      proactive individuals. An acute and active response may be evolutionarily
      maladaptive under chronic, uncontrollable and unpredictable circumstances. It
      appears that subordinate reactive individuals often produce compulsorily chronic
      responses that inhibit aggression and promote submissive behavior.

PMID- 16298362
TI  - Multiplex PCR-based DNA array for simultaneous detection of three human
      herpesviruses, EVB, CMV and KSHV.
AB  - Human lymphotropic herpesviruses, Epstein-Barr virus (EBV), cytomegalovirus (CMV)
      and Kaposi's sarcoma-associated herpesvirus (KSHV) are responsible for a wide
      variety of human diseases. Due to an increase in diseased states associated with
      immunosuppression, more instances of co-morbid infections with these
      herpesviruses have resulted in viral reactivations that have caused numerous
      fatalities. Therefore, the development of rapid and accurate method to detect
      these viruses in immunocompromised patients is vital for immediate treatment with
      antiviral prophylactic drugs. In this study, we developed a new multiplex PCR
      method coupled to DNA array hybridization, which can simultaneously detect all
      three human herpesviruses in one single cell sample. Multiplex PCR primers were
      designed to amplify specific regions of the EBV (EBER1), CMV (IE) and KSHV (LANA)
      viral genomes. Pre-clinical application of this method revealed that this
      approach is capable of detecting as few as 1 copy of the viral genomes for KSHV
      and CMV and 100 copies of the genome for EBV. Furthermore, this highly sensitive
      test showed no cross-reactivity among the three viruses and is capable of
      detecting both KSHV and EBV viral genomes simultaneously in the lymphoblastoid
      cells that have been double infected with both viruses. Thus, this array-based
      approach serves as a rapid and reliable diagnostic tool for clinical
      applications.

PMID- 16298363
TI  - Ordered subset analysis supports a glaucoma locus at GLC1I on chromosome 15 in
      families with earlier adult age at diagnosis.
AB  - Open angle glaucoma (OAG) is a complex disorder with varying etiologies due to
      multiple genes and environmental effects. This genetic heterogeneity can confound
      efforts to map loci. Increased homogeneity in a sample can be achieved using
      either ordered subset analysis (OSA) which groups families, or individual OSA
      (IOSA), which groups individuals based on disease related covariates. Recently,
      GLC1I was mapped to 15q11-13 in families with early adult onset of OAG. We tested
      for linkage to GLC1I in an independent sample of 167 individuals in 25 multiplex
      OAG families of European descent. We carried out nonparametric linkage analysis
      on the complete set of 25 families and obtained a maximum LOD score of 1.00 at
      9.0 cM. Using mean age at diagnosis (AAD) across the affected individuals within
      each family to order the families as a proxy for age at onset, we found a maximum
      OSA LOD score of 2.09 (p=0.021) at 26.1 cM. The mean (+/-s.d.) AAD across the 14
      earlier AAD families that contributed to the OSA LOD score was 50.6 years (+/
      5.38); the mean AAD for the other 1210 later AAD families that did not contribute
      to the OSA LOD score (the high-AAD) was 61.7 years (+/-3.50). We also ran IOSA on
      our families using AAD as our covariate on which to subset affected individuals.
      The maximum LOD score was 1.01 at 14.3 cM when ordering subjects from early to
      late AAD. Ordered subset analysis of this sample has provided evidence of linkage
      close to the previously identified GLC1I glaucoma locus on 15q11-13 in families
      with middle-aged mean age at diagnosis.

PMID- 16298364
TI  - Differentiation of human adult CD34+ stem cells into cells with a neural
      phenotype: role of astrocytes.
AB  - It has recently been reported that adult hematopoietic stem cells can
      differentiate into neural cells, opening new frontiers in therapy for
      neurodegenerative diseases. In this study, adult human hematopoietic stem cells
      (HSCs) were isolated via magnetic bead sorting, using a specific CD34 antibody
      and cultured with human astrocyte culture conditioned medium (ACM). In order to
      evaluate their differentiation into neurons and/or astrocytes, ACM-treated
      cultures were probed for the expression of several neural markers. We observed
      morphological modifications and, after 20 days of treatment, cell morphology
      displayed extending processes. Immunocytochemistry, Western blotting and RT-PCR
      showed the expression of neuronal markers such as neurofilaments, neuron specific
      enolase (NSE) and NeuN in ACM-treated HSCs cultured in poly-L-lysine-coated
      dishes. On the contrary, when the same ACM-treated cells were grown on a plastic
      substrate, they expressed high levels of glial fibrillary acidic protein (GFAP),
      with only weak expression of neuronal markers. Nestin, a neural progenitor cell
      marker, was present in treated cells, regardless of the substrate. These results
      demonstrate that astrocytes can generate a suitable microenvironment for inducing
      HSCs to differentiate into neural cells. Therefore, adult bone marrow may
      represent a readily accessible source of cells for treating neurodegenerative
      diseases.

PMID- 16298365
TI  - IL-4 modulates the histamine content of mast cells in a mast cell/fibroblast co
      culture through a Stat6 signaling pathway in fibroblasts.
AB  - IL-4 plays a crucial role in the pathogenesis of allergic diseases, such as the
      induction of IgE synthesis and the development of mast cells. To further
      understand the effect of IL-4 on mast cells in skin, we utilized a mast
      cell/fibroblast co-culture system as an in vitro model of dermal mast cells. IL-4
      induced mast cell growth in the culture with fibroblasts. Immunoblot analysis
      revealed that IL-4 activated Stat6 in both mast cells and fibroblasts. The over
      expression of dominant-negative Stat6 in fibroblasts in the presence of IL-4
      decreased the histamine content per mast cell, but not the number of mast cells.
      In contrast, the over-expression of constitutively-active Stat6 in fibroblasts
      increased the histamine content per mast cell, indicating that the activation of
      Stat6 in fibroblasts supports the maturation of mast cells co-cultured with
      fibroblasts.

PMID- 16298366
TI  - Crystal structure of Escherichia coli SufA involved in biosynthesis of iron
      sulfur clusters: implications for a functional dimer.
AB  - IscA and SufA are paralogous proteins that play crucial roles in the biosynthesis
      of Fe-S clusters, perhaps through a mechanism involving transient Fe-S cluster
      formation. We have determined the crystal structure of E. coli SufA at 2.7A
      resolution. SufA exists as a homodimer, in contrast to the tetrameric
      organization of IscA. Furthermore, a C-terminal segment containing two essential
      cysteine residues (Cys-Gly-Cys), which is disordered in the IscA structure, is
      clearly visible in one molecule (the alpha1 subunit) of the SufA homodimer.
      Although this segment is disordered in the other molecule (the alpha2 subunit),
      computer modeling of this segment based on the well-defined conformation of
      alpha1 subunit suggests that the four cysteine residues (Cys114 and Cys116 in
      each subunit) in the Cys-Gly-Cys motif are positioned in close proximity at the
      dimer interface. The arrangement of these cysteines together with the nearby
      Glu118 in SufA dimer may allow coordination of an Fe-S cluster and/or an Fe atom.

PMID- 16298367
TI  - Polyomavirus EGFP-pseudocapsids: analysis of model particles for introduction of
      proteins and peptides into mammalian cells.
AB  - A vector for preparation of mouse polyomavirus capsid-like particles for transfer
      of foreign peptides or proteins into cells was constructed. Model pseudocapsids
      carrying EGFP fused with the C-terminal part of the VP3 minor protein (EGFP-VLPs)
      have been prepared and analysed for their ability to be internalised and
      processed by mouse cells and to activate mouse and human dendritic cells (DC) in
      vitro. EGFP-VLPs entered mouse epithelial cells, fibroblasts and human and mouse
      DC efficiently and were processed by both, lysosomes and proteasomes.
      Surprisingly, they did not induce upregulation of DC co-stimulation molecules or
      maturation markers in vitro; however, they did induce interleukin 12 secretion.

PMID- 16298368
TI  - The Arg473Cys-neuroligin-1 mutation modulates NMDA mediated synaptic transmission
      and receptor distribution in hippocampal neurons.
AB  - Synapses mediate communication between neurons, thus playing a fundamental role
      in information processing in the CNS. Neuroligins form a family of heterophilic
      synaptic cell adhesion molecules, and neuroligin 1 (NL1) has been shown to be
      involved in the formation of excitatory synapses and have been suggested to
      associate indirectly with NMDA receptors by common binding to PSD95. A mutation
      in neuroligin 3 (Arg451Cys-NL3, human sequence numbering) identified in autistic
      patients is associated with altered spine density and has reduced binding
      capacity for its presynaptic partner beta-neurexin. Here, we investigated the
      role of NL1 and the homologous NL1 mutation Arg473Cys-NL1 (R473C-NL1) in
      excitatory synaptic transmission and NMDA receptor distribution. We demonstrate
      that R473C-NL1, when expressed in cultured hippocampal neurons, can induce a
      dramatic increase in NMDA current amplitude and that this change is accompanied
      by NMDA receptor clustering in the postsynaptic cell.

PMID- 16298370
TI  - Chlamydia pneumoniae seropositivity in women with pre-eclampsia.

PMID- 16298369
TI  - Malonyl-CoA decarboxylase is present in the cytosolic, mitochondrial and
      peroxisomal compartments of rat hepatocytes.
AB  - A role for cytosolic malonyl-CoA decarboxylase (MCD) as a regulator of fatty acid
      oxidation has been postulated. However, there is no direct evidence that MCD is
      present in the cytosol. To address this issue, we performed cell fractionation
      and electron microscopic colloidal gold studies of rat liver to determine the
      location and activity of MCD. By both methods, substantial amounts of MCD protein
      and activity were found in the cytosol, mitochondria and peroxisomes, the latter
      with the highest specific activity. MCD species with different electrophoretic
      mobility were observed in the three fractions. The data demonstrate that active
      MCD is present in the cytosol, mitochondria and peroxisomes of rat liver,
      consistent with the view that MCD participates in the regulation of cytosolic
      malonyl-CoA levels and of hepatic fatty acid oxidation.

PMID- 16298371
TI  - Increased apolipoprotein C-III levels associated with insulin resistance
      contribute to dyslipidemia in normoglycemic and diabetic subjects from a
      triethnic population.
AB  - Despite the major role of insulin in regulating apolipoprotein C-III (apo C-III)
      production, little is known about the relationship between apo C-III and insulin
      resistance. We examined this relationship, and the association of apo C-III with
      dyslipidemia, in a triethnic sample of 168 subjects with normoglycemia or type 2
      diabetes. African-Americans had lower triglycerides (1.21 +/- 0.11 mmol/l)
      compared with Hispanics (2.01 +/- 0.14 mmol/l) and white non-Hispanics (1.83 +/-
      0.15 mmol/l), regardless of gender and type 2 diabetes status (P < 0.01), but
      this difference was partially accounted for by ethnic difference in apo C-III
      levels. Metabolic syndrome was associated with high apo C-III (> 14 mg/dl) in
      Hispanics (OR = 5.6; 95%CI: 1.3-23.4) and white non-Hispanics (OR = 6.9; 95%CI:
      1.3-36.4), but not in African-Americans. Apo C-III was the best predictor of
      triglycerides (R2 = 0.54, P < 0.001), after accounting for demographic and
      clinical variables. We found an inverse relationship between apo C-III levels and
      low-density lipoprotein (LDL) particle size in the type 2 diabetes subjects with
      (r = -0.36, P = 0.02) and without (r = -0.47, P = 0.02) the metabolic syndrome,
      but in normoglycemic subjects an inverse relationship was evident only in
      metabolic syndrome subjects (r = -0.52, P < 0.01). These results suggest that
      higher apo C-III may contribute to the increased cardiovascular risk in subjects
      with insulin resistance and type 2 diabetes through its effects on triglycerides
      and LDL particle size.

PMID- 16298372
TI  - LpA-I, LpA-I:A-II HDL and CHD-risk: The Framingham Offspring Study and the
      Veterans Affairs HDL Intervention Trial.
AB  - OBJECTIVE: We tested the hypothesis that concentrations of LpA-I and/or LpA-I:A
      II HDL subclasses are significantly associated with CHD prevalence and recurrent
      cardiovascular events. METHODS: LpA-I levels were determined by differential
      electroimmunoassay in male participants with (n = 169) and without CHD (n = 850)
      from the Framingham Offspring Study (FOS) and in male participants with CHD from
      the placebo arm of the Veterans Affairs HDL Intervention Trial (VA-HIT) (n =
      741). Data were analyzed cross-sectionally (FOS) and prospectively (VA-HIT) and
      were adjusted for established lipid and non-lipid CHD risk factors. RESULTS: We
      observed slightly but significantly higher LpA-I levels in CHD cases compared to
      all or to HDL-C-matched controls and slightly but significantly higher LpA-I:A-II
      levels in CHD cases compared to HDL-C-matched controls it the FOS. Neither LpA-I
      nor LpA-I:A-II levels were significantly different between groups with and
      without recurrent cardiovascular events in the VA-HIT. No significant differences
      were observed in LpA-I and LpA-I:A-II levels in low HDL-C (< or = 40 mg/dl)
      subjects with CHD (VA-HIT, n = 711) and without CHD (FOS, n = 373). Plasma LpA-I
      concentration had a positive correlation with the large LpA-I HDL particle (alpha
      1) but no correlation with the small LpA-I HDL particle (prebeta-1). LpA-I:A-II
      concentration had a positive correlation with the large (alpha-2) and an inverse
      correlation with the small (alpha-3) LpA-I:A-II HDL particles. CONCLUSION: Our
      data do not support the hypothesis that CHD prevalence (FOS) or recurrence of
      cardiovascular events (VA-HIT) are associated with significant reductions in the
      concentrations of LpA-I and/or LpA-I:A-II HDL subclasses.

PMID- 16298374
TI  - Influence of the postion of crew members on aerodynamics performance of two-man
      bobsleigh.
AB  - Bobsleigh aerodynamics has long been recognised as one of the crucial performance
      factors. Although the published research in the area is very limited, it is well
      known that the leading nations in the sport devote significant resources in
      research and development of sleds' aerodynamics. However, the rules and
      regulations pose strict design constraints on the shape modifications aiming at
      aerodynamics improvements. The reason for that is two-fold: (i) safety of the
      athletes and (ii) reduction of equipment impact on competition outcome. One
      particular area that has not been looked at and falls outside the current rules
      and regulations is the influence of the crew positioning and internal
      modifications on the aerodynamic performance. The current study presents results
      on numerical simulation of the flow in the cavity underpinned with some
      experimental measurements including flow visualisation of the air circulation
      around the bobsleigh. A simplified computational model was developed to assess
      the trends and its results validated by windtunnel tests. The results show that
      crew members influence the drag level significantly and suggest that purely
      internal modifications can be introduced to reduce the overall resistance drag.

PMID- 16298373
TI  - A comparison of the effects of A1 and A2 beta-casein protein variants on blood
      cholesterol concentrations in New Zealand adults.
AB  - Beta-casein is a cow's milk protein that occurs predominantly in two forms, A1
      and A2. Epidemiological evidence suggests that per capita consumption of beta
      casein A1 is associated with national mortality rates from ischaemic heart
      disease. A biological mechanism was proposed after rabbits fed diets containing
      beta-casein A2 had lower serum cholesterol concentrations and less aortic intimal
      thickening than rabbits fed beta-casein A1. We tested whether beta-casein A1 and
      A2 variants differentially affect plasma cholesterol concentrations in humans. In
      a randomised crossover trial of two four-and-a-half week periods without washout,
      62 participants replaced all dairy products in their diet with 500 mL of low-fat
      milk and 28 g of full-fat cheese that differed in the proportion of beta-casein
      A1 and A2 variants. Duplicate blood samples were taken on non-consecutive days at
      the end of each treatment period from 55 people who completed the study. Mean
      (S.D.) plasma total, low-density and high-density lipoprotein cholesterol
      concentrations were 5.60 (0.77), 3.73 (0.70) and 1.26 (0.34) mmol/L after the A1
      diet and 5.63 (0.81), 3.75 (0.75) and 1.27 (0.37) mmol/L after the A2 diets. We
      found no evidence that dairy products containing beta-casein A1 or A2 exerted
      differential effects (P > 0.05) on plasma cholesterol concentrations in humans.

PMID- 16298375
TI  - Can the growth factors PTHrP, Ihh and VEGF, together regulate the development of
      a long bone?
AB  - Endochondral ossification is the process of differentiation of cartilaginous into
      osseous tissue. Parathyroid hormone related protein (PTHrP), Indian hedgehog
      (Ihh) and vascular endothelial growth factor (VEGF), which are synthesized in
      different zones of the growth plate, were found to have crucial roles in
      regulating endochondral ossification. The aim of this study was to evaluate
      whether the three growth factors PTHrP, Ihh and VEGF, together, could regulate
      longitudinal growth in a normal human, fetal femur. For this purpose, a one
      dimensional finite element (FE) model, incorporating growth factor signaling, was
      developed of the human, distal, femoral growth plate. It included growth factor
      synthesis in the relevant zones, their transport and degradation and their
      effects. Simulations ran from initial hypertrophy in the center of the bone until
      secondary ossification starts at approximately 3.5 months postnatal. For clarity,
      we emphasize that no mechanical stresses were considered. The FE model showed a
      stable growth plate in which the bone growth rate was constant and the number of
      cells per zone oscillated around an equilibrium. Simulations incorporating
      increased and decreased PTHrP and Ihh synthesis rates resulted, respectively, in
      more and less cells per zone and in increased and decreased bone growth rates.
      The FE model correctly reflected the development of a growth plate and the rate
      of bone growth in the femur. Simulations incorporating increased and decreased
      PTHrP and Ihh synthesis rates reflected growth plate pathologies and growth
      plates in PTHrP-/- and Ihh-/- mice. The three growth factors, PTHrP, Ihh and
      VEGF, could potentially together regulate tissue differentiation.

PMID- 16298376
TI  - High performance liquid chromatography/electrospray ionization mass spectrometry
      for simultaneous analysis of alkamides and caffeic acid derivatives from
      Echinacea purpurea extracts.
AB  - Extracts of the plant Echinacea purpurea are widely used for medicinal purposes.
      Effective quality control of these extracts requires rapid methods to determine
      their chemical composition. A new method for analysis of caffeic acid derivatives
      and alkamides from Echinacea extracts has been developed. With this method,
      isomeric isobutylamides and 2-methylbutylamides can be distinguished, a
      capability that previously published methods have lacked. Quantitative analyses
      carried out with this method on E. purpurea extracts that have been stored for 18
      months indicate that they contain caftaric acid, cichoric acid, and undeca-2Z,4E
      diene-8,10-diynoic acid isobutylamide at concentrations of 0.7, 0.71 and
      2.0mg/mL, respectively.

PMID- 16298377
TI  - High-performance liquid chromatography of aromatic compounds with photochemical
      decomposition and tris(2,2'-bipyridine)ruthenium(III) chemiluminescence
      detection.
AB  - A novel high-performance liquid chromatographic method for the determination of
      aromatic compounds based on the on-line photochemical degradation and subsequent
      tris(2,2'-bipyridine)ruthenium(III) chemiluminescence detection has been
      developed. Chemiluminescence intensity depended upon the number of aromatic
      rings, UV irradiation time, and variety of substituted functional groups. One of
      the decomposition products of aromatic compounds by UV irradiation was identified
      as oxalic acid. As one application of this methodology, determination of
      catechins in tea has been shown. Calibration graphs, based on standard (-)
      epicatechin and (-)-epigallocatechin gallate solutions, were linear over the
      range of 0.1-50 microM. The detection limits (signal-to-noise ratio=3) were 0.8
      pmol for (-)-epigallocatechin gallate and 1.2 pmol for (-)-epicatechin. The high
      performance liquid chromatography-chemiluminescence (HPLC-CL) detection method
      with a post-column photochemical reactor can be applied to the sensitive and
      selective determination of catechins in tea.

PMID- 16298378
TI  - Improved high performance liquid chromatographic method for determination of
      carotenoids in the microalga Chlorella pyrenoidosa.
AB  - Microalgae have become an important commercial source of carotenoids and
      microalgae-derived functional foods are consumed by people worldwide. Therefore,
      an HPLC method was developed to discern the variety and content of carotenoids in
      the microalga Chlorella pyrenoidosa. The microalga sample was powdered,
      extracted, saponified and subjected to HPLC analysis. A mobile phase of methanol
      acetonitrile-water (84:14:2, v/v/v) (A) and methylene chloride (100%) (B) with
      the following gradient elution was developed: 100% A and 0% B in the beginning,
      maintained for 14 min, decreased to 95% A in 25 min, 75% A in 30 min, 74% A in 35
      min, 45% A in 50 min and returned to 100% A in 55 min. A total of 32 carotenoids
      were resolved within 49 min by using a C30 column with flow rate at 1 mL/min and
      detection at 450 nm. An internal standard beta-apo-8'-carotenal was used to
      quantify all the carotenoids. All-trans-lutein was present in exceptionally large
      amount (125034.4 microg/g), followed by cis isomers of lutein (27975.3 microg/g),
      all-trans-alpha-carotene (2465.8 microg/g), zeaxanthin (2170.3 microg/g), cis
      isomers of beta-carotene (2159.3 microg/g), all-trans-beta-carotene (2155.0
      microg/g), cis isomers of alpha-carotene (1766.7 microg/g), beta-cryptoxanthin
      (334.9 microg/g), neoxanthin and its cis isomers (199.7 microg/g), neochrome
      (65.2 microg/g), auroxanthin (38.5 microg/g) and violaxanthin and its cis isomers
      (38.1 microg/g).

PMID- 16298379
TI  - Adsorption of a reactive dye on chemically modified activated carbons--influence
      of pH.
AB  - The surface chemistry of a commercial activated carbon with a slightly basic
      nature was modified by appropriate treatments in order to obtain two additional
      samples, respectively with acidic and basic properties, without changing its
      textural parameters significantly. Different techniques (N2 adsorption at 77 K,
      temperature programmed desorption, and determination of acidity, basicity, and pH
      at the point of zero charge) were used to characterize the adsorbents. Kinetic
      and equilibrium adsorption data of a selected textile reactive dye (Rifafix Red
      3BN, C.I. reactive red 241) on the mentioned materials were obtained at the pH
      values of 2, 7, and 12. The kinetic curves are fitted using the second-order
      model. The respective rate constants seem to diminish progressively with the
      initial concentration for the more diluted solutions tested, reaching a constant
      value at higher concentrations, which depends on the experimental system under
      consideration (adsorbent and pH). In general, the Langmuir model provides the
      best fit for the equilibrium data. The different uptakes obtained are discussed
      in relation to the surface chemical properties of the adsorbents. It is shown
      that the adsorption of the reactive (anionic) dye on the basic sample (prepared
      by thermal treatment under H2 flow at 700 degrees C) is favored. This conclusion
      is explained on the basis of the dispersive and electrostatic interactions
      involved. Moreover, it is also shown that the optimal adsorption condition for
      all the activated carbons tested corresponds to solution pH values not higher
      than the pH(pzc) of the adsorbents, which may be interpreted by taking into
      account the electrostatic forces present.

PMID- 16298380
TI  - Adsorption of polyvinylimidazole onto kaolinite.
AB  - The adsorption of polyvinylimidazole (PVI) onto kaolinite from aqueous solutions
      has been investigated systematically as a function of parameters such as
      calcination temperature of kaolinite, pH, ionic strength, and temperature.
      According to the experimental results, the adsorption of PVI increases with pH
      from 8.50 to 11.50, temperature from 25 to 55 degrees C, and ionic strength from
      0 to 0.1 mol L(-1). The kaolinite sample calcined at 600 degrees C has a maximum
      adsorption capacity. Adsorption isotherms of PVI onto kaolinite have been
      determined and correlated with common isotherm equations such as Langmuir and
      Freundlich isotherm models. The Langmuir isotherm model appeared to fit the
      isotherm data better than the Freundlich isotherm model. The physical properties
      of this adsorbent are consistent with the parameters obtained from the isotherm
      equations. Furthermore, the zeta potentials of kaolinite suspensions have been
      measured in aqueous solutions of different PVI concentrations and pH. From the
      experimental results, (i) pH strongly alters the zeta potential of kaolinite;
      (ii) kaolinite has an isoelectric point at about pH 2.35 in water and about pH
      8.75 in 249.9 ppm PVI concentration; (iii) PVI changes the interface charge from
      negative to positive for kaolinite. The study of temperature effect has been
      quantified by calculating various thermodynamic parameters such as Gibbs free
      energy, enthalpy, and entropy changes. The dimensionless separation factor (RL)
      has shown that kaolinite can be used for adsorption of PVI from aqueous
      solutions.

PMID- 16298381
TI  - Water mass transfer in W/O emulsions.
AB  - Water transportation through the oil phase in W/O emulsions and in W1/O/W2
      systems (W/O emulsion in contact with water) was examined. Substance diffusion
      through interfaces led to interface instability and spontaneous emulsification
      which caused nanodispersion formation. The photomicrographs of Pt/C replicas of
      emulsions showed the presence in the continuous oil phase a lot of nanodispersion
      droplets with a diameter in the range 17-25 nm. Diffusion coefficient (D) of
      water calculated on the base of Lifshiz-Slezov-Wagner (LSW) equation was about 15
      times lower than the coefficients of molecular diffusion. Since such emulsions
      were extremely unstable toward coalescence, the growth of water droplets took
      place through as Ostwald ripening as coalescence. In three-phase W1/O/W2 systems
      diffusion of water, Rhodamine C, and ethanol was studied. D calculated on the
      base of the equation of nonstationary diffusion were approximately 1000 times
      lower than molecular ones. It was assumed, that nanodispersion droplets were more
      likely water carriers in investigated W/O emulsions stabilized by sorbitan
      monooleate.

PMID- 16298382
TI  - The influence of temperature on the adsorption of mellitic acid onto goethite.
AB  - The adsorption of mellitic acid (benzene-1,2,3,4,5,6-hexacarboxylic acid) onto
      goethite was investigated at five temperatures between 10 and 70 degrees C.
      Mellitic acid adsorption increased with increasing temperature below pH 7.5, but
      at higher pH the effect of increasing temperature was to reduce the amount
      adsorbed. Potentiometric titrations were conducted and adsorption isotherms were
      measured over the same temperature range, and the data obtained were used in
      conjunction with adsorption edge data to develop an Extended Constant Capacitance
      Surface Complexation Model of mellitic acid adsorption. A single set of reactions
      was used to model the adsorption for the three different experiment types at the
      five temperatures studied. The adsorption reactions proposed for mellitate ion
      (L(6-)) adsorption at the goethite surface (SOH) involved the formation of two
      outer-sphere complexes: SOH + L(6-) + 3H+ <==> [(SOH2)+ (LH2)(4-)]3-, 2SOH + L(6
      ) + 2H+ <==> [(SOH2)2(2+) (L)(6-)]4-. This mechanism is consistent with recent
      ATR-FTIR spectroscopic measurements of the mellitate-goethite system.
      Thermodynamic parameters calculated from the temperature dependence of the
      equilibrium constants for these reactions indicate that the adsorption of
      mellitic acid onto goethite is accompanied by a large entropy increase.

PMID- 16298383
TI  - Unsmooth cuticles of soil animals and theoretical analysis of their
      hydrophobicity and anti-soil-adhesion mechanism.
AB  - Soil adhesion is a natural phenomenon, and it is harmful to terrain machines and
      tillage equipment that have soil as their work medium, such as automobiles,
      tractors, earth-moving machines, spades, hoes, and plows. Soil adhesion increases
      motion resistance and energy consumption, quickens damage to the soil-engaging
      components, and lowers work quality. The biomimetic research has provided a
      promising method to solve the soil adhesion problem. In this work, the cuticles
      of typical soil animals were observed by scanning electron microscopy (SEM) and
      their wettability and mechanism of antiadhesion were analyzed in theory. The
      results of experimental observation have shown that the cuticles of soil animals
      have different unsmooth appearances, such as pimple-shaped, pit-like, and undee
      structures. But for the cross sections of the unsmooth cuticles, their common
      character is undee. Theoretical analysis has indicated that the larger the ratio
      of the amplitude of the wave to the period of the wave, the stronger the
      hydrophobicity, the more easily the composite interface between the liquid and
      the unsmooth cuticles forms, and the function of reducing soil adhesion of the
      unsmooth cuticles will be better.

PMID- 16298384
TI  - Structure modifications of AOT reverse micelles due to protein incorporation.
AB  - Structural modifications of AOT/water/isooctane reverse micelles due to
      incorporation of proteins were studied at various water contents and protein
      concentrations, using small-angle X-ray scattering (SAXS) experiments under
      static conditions, rheometry analysis, and SR-SAXS experiments under induced
      shear flow. Two proteins, lysozyme (pI 11.1, Mw 14,300 Da) and BSA (pI 4.3, Mw
      66,700 Da), were chosen as models. SAXS analysis of protein-containing reverse
      micelles at low water content detected minima in the average micelle size versus
      protein concentration curve, for both proteins, below and above their isoelectric
      point. This minimum was attributed to changes in the size distribution of the
      reverse micelles. SAXS measurements of reverse micelles at high water content
      have shown them to have a cylindrical form. Incorporation of lysozyme at pH 7
      into the cylindrical micelles induced a shape transition to spherical micelles,
      which was associated with a decreased viscosity. SR-SAXS measurements under
      induced shear flow and dynamic conditions revealed alignment of the cylindrical
      micelles in the flow direction. The anisotropy parameter, a measure of the degree
      of the spatial order, was found to increase with increasing shear rate and to
      decrease with increasing lysozyme concentration.

PMID- 16298385
TI  - Sorption of bisphenol A, 17alpha-ethynylestradiol and estrone to mineral
      surfaces.
AB  - Sorption of the endocrine disrupting chemicals (EDCs) bisphenol A (BPA), 17alpha
      ethynylestradiol (EE2) and estrone (E1) from 3 microM aqueous solutions in 10 mM
      KNO3 to goethite, kaolinite and montmorillonite was investigated at 25 degrees C.
      Uptake of the EDCs by goethite and kaolinite suspensions was <20%, and little
      affected by pH. Sorption by montmorillonite was greater, ranging from 20 to 60%,
      and steadily increased from about pH 7. The amount of EDC sorbed to the mineral
      phases generally increased in the order of decreasing solubility (BPA<EE2<E1).
      Sorption to goethite and kaolinite was rapid (<10 min), but much slower for
      montmorillonite, to which sorption continued for 24-48 h. Although the EDCs
      desorbed rapidly and completely from goethite and kaolinite, only small amounts
      desorbed from montmorillonite below pH 7, and no recovery was observed at pH 10.
      The kinetic and desorption experiments indicate that the EDCs intercalate into
      the interlayer spaces of montmorillonite, but for goethite and kaolinite sorption
      probably occurs at external surfaces.

PMID- 16298386
TI  - The effects of added nanoparticles on aqueous kaolinite suspensions. I.
      Structural effects.
AB  - The results of an experimental study focused on the effect of added silica
      nanospheres on the structure of an aqueous suspension of disc-shaped kaolinite
      particles are presented. In the absence of any additives, kaolinite particles
      rapidly aggregate and settle. When only nanoparticles were added to a 14% vol.
      kaolinite suspension, some stabilization was observed, although a thick, fluid
      like sediment still formed. Adding both nanoparticles and salt (NaCl or KCl),
      however, caused the entire suspension to transition into a solid material that
      was strong enough to actually be sliced. A phase diagram was constructed showing
      the concentration of salt and nanoparticles needed to produce this transition.
      With smaller nanoparticles, the transition occurred at much lower nanoparticle
      volume fractions. Scanning electron micrographs of both the sediment and solid
      like material, obtained by cryogenic drying, showed that the latter consisted of
      a porous, 'sponge-like' structure. The characteristic size of the pores decreased
      as the number density of the added nanoparticles increased. Although the
      nanoparticles were not visible in the SEM images, it is believed that they had
      separated into the pores of the solid-like material. While a similar type of
      transition could be produced in suspensions containing only the silica
      nanospheres, the structure and flow behavior of this material were markedly
      different from that obtained with the added clay.

PMID- 16298387
TI  - Insights into the quality of DnaA boxes and their cooperativity.
AB  - Plasmids carrying the mioC promoter region with its two DnaA boxes are as
      efficient in titration of DnaA protein as plasmids carrying a replication
      inactivated oriC region with its five DnaA boxes. The two DnaA boxes upstream of
      the mioC promoter were mutated in various ways to study the cooperativity between
      the DnaA boxes, and to study in vivo the in vitro-defined 9mer DnaA box consensus
      sequence (TT(A)/(T)TNCACA). The quality and cooperativity of the DnaA boxes were
      determined in two complementary ways: as titration of DnaA protein leading to
      derepression of the dnaA promoter, and as repression of the mioC promoter caused
      by the DnaA protein binding to the DnaA boxes. Titration of DnaA protein
      correlated with repression of the mioC promoter. The level of titration and
      repression with the normal promoter-proximal box (TTTTCCACA) depends strongly on
      the presence and the quality of a DnaA box in the promoter-distal position,
      whereas a promoter-proximal DnaA box with the sequence TTATCCACA titrated DnaA
      protein and caused significant repression of the mioC promoter without a promoter
      distal DnaA box. The quality of the eight different consensus DnaA boxes located
      in the promoter-proximal position was determined: TTATCCACA had the highest
      affinity for DnaA protein. In the third position, A was better than T, and the
      four possibilities in the fifth position could be ranked as C >A >or=G >T.
      Parallel in vitro experiments using a purified DNA-binding domain of DnaA protein
      gave the same ranking of the binding affinities of the eight DnaA boxes.

PMID- 16298388
TI  - Structural basis of the suppressed catalytic activity of wild-type human
      glutathione transferase T1-1 compared to its W234R mutant.
AB  - The crystal structures of wild-type human theta class glutathione-S-transferase
      (GST) T1-1 and its W234R mutant, where Trp234 was replaced by Arg, were solved
      both in the presence and absence of S-hexyl-glutathione. The W234R mutant was of
      interest due to its previously observed enhanced catalytic activity compared to
      the wild-type enzyme. GST T1-1 from rat and mouse naturally contain Arg in
      position 234, with correspondingly high catalytic efficiency. The overall
      structure of GST T1-1 is similar to that of GST T2-2, as expected from their 53%
      sequence identity at the protein level. Wild-type GST T1-1 has the side-chain of
      Trp234 occupying a significant portion of the active site. This bulky residue
      prevents efficient binding of both glutathione and hydrophobic substrates through
      steric hindrance. The wild-type GST T1-1 crystal structure, obtained from co
      crystallization experiments with glutathione and its derivatives, showed no
      electron density for the glutathione ligand. However, the structure of GST T1-1
      mutant W234R showed clear electron density for S-hexyl-glutathione after co
      crystallization. In contrast to Trp234 in the wild-type structure, the side-chain
      of Arg234 in the mutant does not occupy any part of the substrate-binding site.
      Instead, Arg234 is pointing in a different direction and, in addition, interacts
      with the carboxylate group of glutathione. These findings explain our earlier
      observation that the W234R mutant has a markedly improved catalytic activity with
      most substrates tested to date compared to the wild-type enzyme. GST T1-1
      catalyzes detoxication reactions as well as reactions that result in toxic
      products, and our findings therefore suggest that humans have gained an
      evolutionary advantage by a partially disabled active site.

PMID- 16298389
TI  - PU.1/Spi-1 binds to the human TAL-1 silencer to mediate its activity.
AB  - The TAL-1/SCL gene encodes a basic helix-loop-helix (bHLH) transcription factor
      essential for primitive hematopoiesis and for adult erythroid and megakaryocytic
      development. Activated transcription of TAL-1 as a consequence of chromosomal
      rearrangements is associated with a high proportion of human T cell acute
      leukemias, showing that appropriate control of TAL-1 is crucial for the formation
      and subsequent fate of hematopoietic cells. Hence, the knowledge of the
      mechanisms, which govern the pattern of TAL-1 expression in hematopoiesis, is of
      great interest. We previously described a silencer in the 3'-untranslated region
      of human TAL-1, the activity of which is mediated through binding of a tissue
      specific 40 kDa nuclear protein to a new DNA recognition motif, named tal-RE.
      Here, we show that tal-RE-binding activity, high in immature human hematopoietic
      progenitors is down regulated upon erythroid and megakaryocytic differentiation.
      This expression profile helped us to identify that PU.1/Spi-1 binds to the tal-RE
      sequences in vitro and occupies the TAL-1 silencer in vivo. By expressing a
      mutant protein containing only the ETS domain of PU.1 in human erythroleukemic
      HEL cells, we demonstrated that PU.1 mediates the transcriptional repression
      activity of the silencer. We found that ectopic PU.1 is not able to induce
      silencing activity in PU.1-negative Jurkat T cells, indicating that PU.1
      activity, although necessary, is not sufficient to confer transcriptional
      repression activity to the TAL-1 silencer. Finally, we showed that the silencer
      is also active in TAL-1-negative myeloid HL60 cells that express PU.1 at high
      levels. In summary, our study shows that PU.1, in addition to its positive role
      in TAL-1 expression in early hematopoietic progenitors, may also act as a
      mediator of TAL-1 silencing in some hematopoietic lineages.

PMID- 16298390
TI  - Observing folding pathways and kinetics of a single sodium-proton antiporter from
      Escherichia coli.
AB  - Mechanisms of folding and misfolding of membrane proteins are of interest in cell
      biology. Recently, we have established single-molecule force spectroscopy to
      observe directly the stepwise folding of the Na+/H+ antiporter NhaA from
      Escherichia coli in vitro. Here, we improved this approach significantly to track
      the folding intermediates of a single NhaA polypeptide forming structural
      segments such as the Na+-binding site, transmembrane alpha-helices, and helical
      pairs. The folding rates of structural segments ranged from 0.31 s(-1) to 47 s(
      1), providing detailed insight into a distinct folding hierarchy of an unfolded
      polypeptide into the native membrane protein structure. In some cases, however,
      the folding chain formed stable and kinetically trapped non-native structures,
      which could be assigned to misfolding events of the antiporter.

PMID- 16298391
TI  - Nuclear sequestration of beta-subunits by Rad and Rem is controlled by 14-3-3 and
      calmodulin and reveals a novel mechanism for Ca2+ channel regulation.
AB  - Voltage-gated Ca2+ channels (VDCCs) are heteromultimeric proteins that mediate
      Ca2+ influx into cells upon membrane depolarization. These channels are involved
      in various cellular events, including gene expression, regulation of hormone
      secretion and synaptic transmission. Kir/Gem, Rad, Rem, and Rem2 belong to the
      RGK family of Ras-related small G proteins. RGK proteins interact with the beta
      subunits and downregulate VDCC activity. Kir/Gem was proposed to prevent surface
      expression of functional Ca2+ channels, while for Rem2 the mechanism remains
      controversial. Here, we have analyzed the mechanism by which Rad and Rem regulate
      VDCC activity. We show that, similar to Kir/Gem and Rem2, 14-3-3 and CaM binding
      regulate the subcellular distribution of Rad and Rem, which both inhibit Ca2+
      channel activity by preventing its expression on the cell surface. This function
      is regulated by calmodulin and 14-3-3 binding only for Rad and not for Rem.
      Interestingly, nuclear targeting of Rad and Rem can relocalize and sequester the
      beta-subunit to the nucleus, thus providing a novel mechanism for Ca2+ channel
      downregulation.

PMID- 16298392
TI  - Crash data and signal coordination: a one-way pair case study.

PMID- 16298393
TI  - Injury severity codes: a comparison of police injury codes and medical outcomes
      as determined by NASS CDS Investigators.

PMID- 16298394
TI  - Advantages and disadvantages of different crash modeling techniques.

PMID- 16298395
TI  - A comparison of aggressive and DUI crashes.

PMID- 16298396
TI  - The risks of driving on roadways with 50 miles per hour posted speed limit.

PMID- 16298397
TI  - Homeland security, car crashes and traffic incident data: killing three birds
      with one IT architecture.

PMID- 16298398
TI  - RNAi-hTERT inhibition hepatocellular carcinoma cell proliferation via decreasing
      telomerase activity.
AB  - BACKGROUND: RNA interference (RNAi), which has been demonstrated as having great
      potentional in the fields of gene function and gene therapy, was applied to
      inhibit the expression of some endogenous genes. Human telomerase reverse
      transcriptase (hTERT) is highly expressed in hepatocellular carcinoma cells.
      MATERIALS AND METHODS: In combination with DNA vector-based RNAi, quantitative
      real-time reverse transcription polymerase chain reaction, telomeric repeat
      amplification protocol-enzyme-linked immunosorbent assay, 3-(4,5
      dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay, and xenograft tumor
      animal techniques, we first constructed three pTZU6 + 1-shRNA-hTERT vectors and
      their corresponding site-mutated vectors, then transfected them into
      hepatocarcinoma HepG2, SMMC-7721 cells, and normal liver L02 cells, respectively,
      injected them into xenograft hepatocarcinoma tumor tissues to induce RNAi, and
      then detected the alteration of cell and tumor proliferation, telomerase
      activity, hTERT, and c-myc expression in each treatment. RESULTS: The cell
      proliferation of hepatocellular carcinoma cells both in vitro and in vivo was
      significantly inhibited by ph1-shRNA, the most effective segment targeted hTERT
      gene. ph1-shRNA could inhibit telomerase activity, hTERT, and c-myc expression in
      hepatocarcinoma cells and xenograft tumor tissues compare with the cells treated
      with empty vector pTZU6 + 1. However, there were no obvious effects on normal
      liver L02 cells. Moreover, even a single base mutation in siRNAs transcription
      template would significantly reduce the ability of siRNAs to induce RNA
      silencing. CONCLUSIONS: RNAi-hTERT could inhibit the proliferation of
      hepatocarcinoma cells specifically via the suppression of telomease activity,
      hTERT, and c-myc expression. Therefore, hTERT and c-myc play key roles in
      hepatocarcinoma tumorgenesis, and an RNAi-targeted hTERT strategy would be a
      potential approach for hepatocarcinoma therapy.

PMID- 16298399
TI  - Evaluation of two different biomarkers for use in the assessment of toxic
      chemical exposure in California sea lions (Zalophus californianus).

PMID- 16298401
TI  - Tapping, grasping and aiming in ideomotor apraxia.
AB  - Very few studies have investigated sensorimotor control in apraxia using tasks
      that differ in movement complexity. Nevertheless, there is some evidence to
      suggest that spontaneous behaviour, although relatively preserved, can be rather
      clumsy or awkward, and that patients with ideomotor apraxia may have subtle
      kinematic abnormalities in movements made in the laboratory. It remains unclear
      whether patients with ideomotor apraxia perform normally on movements such as
      visually guided aiming, that may not depend on higher-order, more cognitive,
      processes and that are relatively unguided by overlearned contexts. In this
      study, three different sensorimotor tasks were given to the same sample of
      patients with quantified apraxic disturbance. Finger tapping, goal-directed
      grasping and aiming with and without visual feedback were examined in these
      patients. A clear dissociation was found between grossly impaired gesture
      imitation and intact motor programming of goal-directed movements with visual
      feedback. Apraxic patients were, however, impaired on aiming movements without
      visual feedback, suggesting that apraxia is associated with an increased reliance
      on integration of online visual information with feedforward/feedback
      somatosensory and motor signals. Furthermore, patients were impaired on single
      finger tapping which was a surprisingly good predictor of apraxia severity.

PMID- 16298400
TI  - BGC20-761, a novel tryptamine analog, enhances memory consolidation and reverses
      scopolamine-induced memory deficit in social and visuospatial memory tasks
      through a 5-HT6 receptor-mediated mechanism.
AB  - Inhibition of 5-HT(6) receptors has been shown to improve memory consolidation,
      thus we tested whether a novel tryptamine analog with high affinity for 5-HT(6)
      receptors, BGC20-761 (5-methoxy-2-phenyl-N,N-dimethyltryptamine, PMDT), can
      enhance long-term memory. BGC20-761 (10 mg/kg i.p.) alone had no effect on social
      recognition in young rats, however, at doses of 5 mg/kg and 10 mg/kg i.p, BGC20
      761 dose-dependently reversed a deficit of social recognition induced by
      scopolamine (0.4 mg/kg i.p.), an anticholinergic drug that impairs memory. BGC20
      761 (10 mg/kg i.p.), scopolamine (0.2 mg/kg i.p.) or BGC20-761 + scopolamine had
      no effects on novel object discrimination in young rats (2 months). In mature
      rats (6 months), recognition of the novel object was improved following
      administration of BGC20-761. Scopolamine had no effect in object recognition.
      However, the addition of scopolamine disrupted the memory-enhancing effect of
      BGC20-761. Based on the high affinity of BGC20-761 for 5-HT(6) receptors, these
      cognitive enhancing effects are most likely mediated by 5-HT(6) receptor
      inhibition. The difference in effects of BGC20-761 in young vs. mature rats may
      reflect the status of memory consolidation in these different age ranges.

PMID- 16298402
TI  - Structures, biogenetic relationships, and cytotoxicity of pimarane-derived
      diterpenes from Petalostigma pubescens.
AB  - Extraction of Petalostigma pubescens heartwood followed by chromatographic
      purifications and crystallizations afforded five tricyclic diterpenes: 5,9-syn
      rosanes petalostigmones A and B (1 and 2), the erythroxylane petalostigmone C
      (3), the norditerpene lactone pubescenone (4), and the known ent-cleistanthane
      diterpene (-)-sonderianol (5). The structures and relative stereochemistry were
      elucidated by means of spectroscopic methods, chemical correlations, and, in the
      cases of 1 and 4, by X-ray crystallographic analyses. The new isolates 1-4 are
      assumed to belong to the same absolute configurational family (9alphaCH3) of ent
      pimarane-derived diterpenes as the known co-occurring (-)-5 (10alphaCH3).
      Biogenetic schemes originating from a common ent-copalyl diphosphate intermediate
      are presented to rationalize the structures of these natural products. A novel
      ring contraction-ring expansion mechanism is suggested to account for the 7
      membered B ring of pubescenone. Compounds 1-5 were evaluated for their
      cytotoxicity; sonderianol (5) showed the highest activity against mouse leukemia
      cell lines L1210, P388 and mouse liver cancer cells HEPA1c1c7.

PMID- 16298404
TI  - Severe acute respiratory syndrome (SARS): knowledge, attitudes, practices and
      sources of information among physicians answering a SARS fever hotline service.
AB  - In June 2003, Taiwan introduced a severe acute respiratory syndrome (SARS)
      telephone hotline service to provide concerned callers with rapid access to
      information, advice and appropriate referral where necessary. This paper reports
      an evaluation of the knowledge, attitude, practices and sources of information
      relating to SARS among physicians who staffed the SARS fever hotline service. A
      retrospective survey was conducted using a self-administered postal
      questionnaire. Participants were physicians who staffed a SARS hotline during the
      SARS epidemic in Taipei, Taiwan from June 1 to 10, 2003. A response rate of 83%
      was obtained. All respondents knew the causative agent of SARS, and knowledge
      regarding SARS features and preventive practices was good. However, only 54% of
      respondents knew the incubation period of SARS. Hospital guidelines and news
      media were the major information sources. In responding to two case scenarios
      most physicians were likely to triage callers at high risk of SARS appropriately,
      but not callers at low risk. Less than half of all respondents answered both
      scenarios correctly. The results obtained suggest that knowledge of SARS was
      generally good although obtained from both medical and non-medical sources.
      Specific knowledge was however lacking in certain areas and this affected the
      ability to appropriately triage callers. Standardized education and assessment of
      prior knowledge of SARS could improve the ability of physicians to triage callers
      in future outbreaks.

PMID- 16298403
TI  - The primary in vivo steroidal alkaloid glucosyltransferase from potato.
AB  - To provide tools for breeders to control the steroidal glycoalkaloid (SGA)
      pathway in potato, we have investigated the steroidal alkaloid
      glycosyltransferase (Sgt) gene family. The committed step in the SGA pathway is
      the glycosylation of solanidine by either UDP-glucose or UDP-galactose leading to
      alpha-chaconine or alpha-solanine, respectively. The Sgt2 gene was identified by
      deduced protein sequence homology to the previously identified Sgt1 gene. SGT1
      has glucosyltransferase activity in vitro, but in vivo serves as the UDP
      galactose:solanidine galactosyltransferase. Two alleles of the Sgt2 gene were
      isolated and its function was established with antisense transgenic lines and in
      vitro assays of recombinant protein. In tubers of transgenic potato (Solanum
      tuberosum) cvs. Lenape and Desiree expressing an antisense Sgt2 gene construct,
      accumulation of alpha-solanine was increased and alpha-chaconine was reduced.
      Studies with recombinant SGT2 protein purified from yeast show that SGT2
      glycosylation activity is highly specific for UDP-glucose as a sugar donor. This
      data establishes the function of the gene product (SGT2), as the primary UDP
      glucose:solanidine glucosyltransferase in vivo.

PMID- 16298405
TI  - Spleen enlargement and genetic diversity of Plasmodium falciparum infection in
      two ethnic groups with different malaria susceptibility in Mali, West Africa.
AB  - The high resistance to malaria in the nomadic Fulani population needs further
      understanding. The ability to cope with multiclonal Plasmodium falciparum
      infections was assessed in a cross-sectional survey in the Fulani and the Dogon,
      their sympatric ethnic group in Mali. The Fulani had lower parasite prevalence
      and densities and more prominent spleen enlargement. Spleen rates in children
      aged 2-9 years were 75% in the Fulani and 44% in the Dogon (P<0.001). There was
      no difference in number of P. falciparum genotypes, defined by merozoite surface
      protein 2 polymorphism, with mean values of 2.25 and 2.11 (P=0.503) in the Dogon
      and Fulani, respectively. Spleen rate increased with parasite prevalence, density
      and number of co-infecting clones in asymptomatic Dogon. Moreover, splenomegaly
      was increased in individuals with clinical malaria in the Dogon, odds ratio 3.67
      (95% CI 1.65-8.15, P=0.003), but not found in the Fulani, 1.36 (95% CI 0.53-3.48,
      P=0.633). The more susceptible Dogon population thus appear to respond with
      pronounced spleen enlargement to asymptomatic multiclonal infections and acute
      disease whereas the Fulani have generally enlarged spleens already functional for
      protection. The results emphasize the importance of spleen function in protective
      immunity to the polymorphic malaria parasite.

PMID- 16298406
TI  - Rapid anti-secretory effects of glucocorticoids in human airway epithelium.
AB  - Glucocorticoids are anti-inflammatory molecules classically described as acting
      through a genomic pathway. Similar to many steroid hormones, glucocorticoids also
      induce rapid non-genomic responses. The present paper provides a general overview
      of the rapid non-genomic effects of glucocorticoids in airway and will be mainly
      focused on a retrospective of the authors work on rapid effects of
      glucocorticoids in airway epithelial cell transport. Using fluorescence
      microscopy, short circuit current measurements in human bronchial epithelial
      (16HBE14o(-)) cells, we reported rapid non-genomic effects of dexamethasone on
      cell signalling and ion transport. Dexamethasone (1 nM) rapidly stimulated
      Na(+)/H(+) exchanger activity and pH(i) regulation in 16HBE14o(-) cells.
      Dexamethasone also produced a rapid decrease of intracellular [Ca(2+)](i) to a
      new steady state concentration and inhibited the large and transient [Ca(2+)](i)
      increase induced by apical adenosine tri-phosphate (ATP). Dexamethasone also
      reduced by 1/3 the Ca(2+)-dependent Cl(-) secretion induced by apical ATP. The
      rapid effects of dexamethasone on intracellular pH and Ca(2+) were not affected
      by inhibitors of transcription, cycloheximide or by the classical glucocorticoid
      and mineralocorticoid receptors antagonists, RU486 and spironolactone,
      respectively. The rapid responses to glucocorticoid were reduced by the
      inhibitors of adenylated cyclase, cAMP-dependent protein kinase (PKA) and mitogen
      activated protein kinase (ERK1/2). Our results demonstrate, that dexamethasone at
      low concentrations, rapidly regulates intracellular pH, Ca(2+) and PKA activity
      and inhibits Cl(-) secretion in human bronchial epithelial cells via a non
      genomic mechanism which neither involve the classical glucocorticoid nor
      mineralocorticoid receptor.

PMID- 16298407
TI  - Effect of dietary calcium propionate on performance, hepatic enzyme activities
      and aflatoxin residues in broilers fed a diet containing low levels of aflatoxin
      B1.
AB  - This study was undertaken to the study toxic effects of aflatoxins and reducing
      toxic effects of calcium propionate on performance, hepatic enzyme activities and
      aflatoxin residues in broilers. Two hundred and seventy 1-day-old hybrid Arbor
      Acor broiler chickens were fed conventional feed for 3 days. Broilers were then
      randomly divided into nine groups of 30 birds each. The nine dietary treatments
      consisted of (1) conventional feed as a negative control diet, (2) 0.25% calcium
      propionate, (3) 0.5% calcium propionate, (4) 50 ppb aflatoxin B1, (5) 50 ppb
      aflatoxin B1 plus 0.25% calcium propionate, (6) 50 ppb aflatoxin B1 plus 0.5%
      calcium propionate, (7) 100 ppb aflatoxin B1, (8) 100 ppb aflatoxin B1 plus 0.25%
      calcium propionate, (9) 100 ppb aflatoxin B1 plus 0.5% calcium propionate. Test
      diets were offered for 6 weeks continuously and the birds were sacrificed.
      Decreased body weight gain, feed consumption and feed conversion ratio were
      observed in aflatoxin treated groups whereas aflatoxin B1-calcium propionate
      supplemented diet groups increased, in comparison to the control group.
      Significant difference was observed after 4 weeks of feeding. Serum samples were
      tested for gamma glutamyl transferase (gamma-GGT), aspartate aminotransferase
      (AST) and alanine aminotransferase (ALT). Gamma-GGT, AST and ALT were
      significantly increased in aflatoxin treated groups, in comparison among the
      dietary treated groups. Muscle and liver tissues were analyzed for aflatoxin
      residues. The residual levels of aflatoxin B1 and aflatoxin M1 were significantly
      higher in liver than in muscle. The levels in the liver and the muscle were
      highest in the aflatoxin B1-supplemented groups and lower in the aflatoxin B1
      calcium propionate supplemented groups. Results of this study indicate that
      addition of calcium propionate to diets containing aflatoxin B1 appears to be
      effective in reducing toxicity. Aflatoxin contamination in broiler feed may cause
      economic losses by lowering body weight gain. Therefore, lower levels of
      aflatoxin B1 in the chicken feeds should be required if all acceptable risk is to
      be avoided. Additionally, the risk of aflatoxins in broiler as a food appears to
      remain very low, although the levels of aflatoxins in human foods should be kept
      as low as possible to reduce the incidence of hepatic cancer.

PMID- 16298408
TI  - Identification and specificity of pilus adsorption proteins of filamentous
      bacteriophages infecting Pseudomonas aeruginosa.
AB  - Filamentous bacteriophages Pf1 and Pf3 infect Pseudomonas aeruginosa strains K
      and O, respectively. We show here that the capsids of these bacteriophages each
      contain a few copies of a minor coat protein (designated g3p) of high molecular
      mass, which serves as a pilus adsorption protein, much like the protein g3p of
      the Ff bacteriophages which infect Escherichia coli. Bacteriophage Pf1 was
      observed to interact with the type IV PAK pilus whereas bacteriophage Pf3
      interacted with the conjugative RP4 pilus and not with the type IV PAO pilus. The
      specificity was found to be mediated by their pilus-binding proteins. This is
      evidence of a conserved pathway of infection among different classes of
      filamentous bacteriophage. However, there are likely to be subtle differences yet
      to be discovered in the way these virions effect entry into their targeted
      bacterial cells.

PMID- 16298409
TI  - Differential localization and turnover of infectious bronchitis virus 3b protein
      in mammalian versus avian cells.
AB  - Infectious bronchitis virus (IBV) 3b protein is highly conserved among group 3
      coronaviruses, suggesting that it is important for infection. A previous report
      (Virology 2003, 311:16-27) indicated that transfected IBV 3b localized to the
      nucleus in mammalian cells using a vaccinia-virus expression system. Although we
      confirmed these findings, we observed cytoplasmic localization of IBV 3b with
      apparent exclusion from the nucleus in avian cells (IBV normally infects
      chickens). IBV 3b was virtually undetectable by microscopy in mammalian cells
      transfected without vaccinia virus and in IBV-infected mammalian cells because of
      a greatly reduced half-life in these cells. A proteasome inhibitor stabilized IBV
      3b in mammalian cells, but had little effect on IBV 3b in avian cells, suggesting
      that rapid turnover of IBV 3b in mammalian cells is proteasome-dependent while
      turnover in avian cells may be proteasome-independent. Our results highlight the
      importance of using cells derived from the natural host when studying coronavirus
      non-structural proteins.

PMID- 16298410
TI  - Genome-wide transcription program and expression of the Rta responsive gene of
      Epstein-Barr virus.
AB  - Infection with Epstein-Barr virus (EBV) usually leads to a latent state in B
      lymphocytes. The virus can be reactivated through two viral transactivators, Zta
      and Rta, leading to a cascade of gene expression. An EBV DNA array was generated
      to analyze the pattern of transcription of the entire EBV genome under various
      conditions. Firstly, a complete set of temporal expression clusters of EBV genes
      was displayed by analyzing the array data of anti-IgG-induced Akata cells. In
      addition to assigning genes of unknown function to the various clusters,
      increasing expression of latent genes, including EBNA2, EBNA3A and EBNA 3C, was
      observed during virus replication. Secondly, gene expression independent of viral
      DNA replication was analyzed in PAA blocked Akata cells and in chemically induced
      Raji cells. Several genes with presumed late functions were found to be expressed
      with early kinetics and independent of viral DNA replication, suggesting possible
      novel functions for these genes. Finally, the EBV array was used to identify Rta
      responsive gene expression in Raji cells, and in the EBV-positive epithelial
      cells NA, using a Zta siRNA strategy. The array data were confirmed by Northern
      blotting, RT-PCR and reporter assays. All the information here thus provides a
      better understanding of the control of EBV lytic gene expression.

PMID- 16298411
TI  - Structure and prevalence of replication silencer-3' terminus RNA interactions in
      Tombusviridae.
AB  - Tombusviridae is a large positive-strand RNA virus family. Tomato bushy stunt
      virus (TBSV), the type virus of this family, has a genome ending with AGCCC(-OH),
      termed the 3'-complementary silencer sequence (3'CSS). The 3'CSS is able to base
      pair with a complementary internally-located sequence, 5'GGGCU, called the
      replication silencer element (RSE). In TBSV, previous compensatory mutational
      analysis of the RSE-3'CSS interaction showed it to be functionally important for
      viral RNA synthesis both in vitro and in vivo. However, these investigations also
      revealed that the RSE and 3'CSS are very sensitive to nucleotide changes, even
      when base pairing potential between the two elements is maintained. Consequently,
      an alternative investigative approach was used in this study where the wild-type
      sequences of these elements were preserved and their surrounding contexts were
      modified. Results from these analyses, using a TBSV DI RNA, revealed important
      new structural requirements necessary for the RSE and 3'CSS to operate in vivo.
      Collectively, the data suggest that accessibility of the elements and their
      proximity to adjoining stem structures are important functional parameters. Based
      on these findings, a working structural model for the TBSV RSE-3'CSS interaction
      is proposed that involves coaxial stacking of adjacent helices at either end of
      the RSE-3'CSS interaction. Components of this structural model are extendable to
      potential RSE-3'CSS interactions that were identified throughout Tombusviridae by
      comparative sequence analysis. This survey also revealed a significant level of
      diversity and modularity with respect to RSEs, 3'CSSs and their structural
      contexts and, moreover, suggests that RSE-3'CSS interactions are prevalent in
      Tombusviridae and related viruses.

PMID- 16298412
TI  - The use of 3D information in face recognition.
AB  - Effects of shading in face recognition have often alluded to 3D shape processing.
      However, research to date has failed to demonstrate any use of important 3D
      information. Stereopsis adds no advantage in face encoding [Liu, C. H., Ward, J.,
      & Young, A. W. (in press). Transfer between 2D and 3D representations of faces.
      Visual Cognition], and perspective transformation impairs rather than assists
      recognition performance [Liu, C. H. (2003). Is face recognition in pictures
      affected by the center of projection? In IEEE international workshop on analysis
      and modeling of faces and gestures (pp. 53-59). Nice, France: IEEE Computer
      Society]. Although evidence tends to rule out involvement of 3D information in
      face processing, it remains possible that the usefulness of this information
      depends on certain combinations of cues. We tested this hypothesis in a
      recognition task, where face stimuli with several levels of perspective
      transformation were either presented in stereo or without stereo. We found that
      even at a moderate level of perspective transformation where training and test
      faces were separated by just 30 cm, the stereo condition produced better
      performance. This provides the first evidence that stereo information can
      facilitate face recognition. We conclude that 3D information plays a role in face
      processing but only when certain types of 3D cues are properly combined.

PMID- 16298413
TI  - Hierarchical integration of individual motions in locally paired-dot stimuli.
AB  - Recent psychophysical studies suggest that there are two types of motion
      integration processes in human visual system, i.e., the local and the global
      integration process. The existence of the local integration process is suggested
      by the vector-average perception in locally paired-dot (LPD) stimuli. Here, we
      investigated the relationship between the two motion integration processes by
      measuring the signal detection thresholds in three corresponding stimuli: (1)
      standard random-dot kinematograms (RDKs), (2) LPD stimuli the individual dot
      motions of which were identical to those of RDKs, and (3) pairwise-averaged
      stimuli the individual dot motions of which corresponded to the vector-averages
      of locally paired motions in LPD stimuli. We found that the thresholds in LPD
      stimuli were similar to those in pairwise-averaged stimuli rather than in RDKs.
      In addition, when dots were paired appropriately, observers could detect coherent
      motions in LPD stimuli even if the proportions of signal dots were less than the
      detection thresholds in corresponding RDKs. These results suggest that the local
      and global integrations of individual motions are carried out hierarchically, and
      that the global motion perception in LPD stimuli does not depend on individual
      dot motions directly, but depends on locally integrated motions.

PMID- 16298414
TI  - Motion-detection thresholds for first- and second-order gratings and plaids.
AB  - The two-stage decomposition-recombination model of 2D motion perception has been
      criticised on the basis that the direction of plaid stimuli can be accurately
      discriminated at speeds so low that the direction of their Fourier components is
      not discriminable. The nature of this gap in performance between gratings and
      plaids was investigated across a range of spatial frequencies and durations for
      first- and second-order stimuli. Motion-detection thresholds were obtained using
      a 2AFC, constant stimuli procedure and it was found that although thresholds for
      detection of plaid motion were often lower than those for gratings, the gap in
      performance between first-order plaids and gratings was unreliable, varying in
      magnitude and occasionally direction with the spatial frequency of the stimulus,
      presentation duration and observer. Curiously, an analogous gap found between
      purely second-order gratings and second-order plaids was more reliable and
      stable. It has been suggested that the gap is the result of 'local motion
      detectors' or broadly tuned V1 cells. The data presented here suggest that second
      order mechanisms are responsible for the gap and that first-order information may
      even disrupt it.

PMID- 16298415
TI  - Non-equilibrium partitioning tracer transport in porous media: 2-D physical
      modelling and imaging using a partitioning fluorescent dye.
AB  - This paper describes an investigation into non-equilibrium partitioning tracer
      transport and interaction with non-aqueous-phase liquid (NAPL) contaminated water
      saturated porous media using a two-dimensional (2-D) physical modelling
      methodology. A fluorescent partitioning tracer is employed within a transparent
      porous model which when imaged by a CCD digital camera can provide full spatial
      tracer concentrations and tracer breakthrough curves. Quasi one-dimensional (1-D)
      benchmarking tests in models packed with various combinations of clean quartz
      sand and NAPL are described. These modelled residual NAPL saturations, S(n), of 0
      15%. Results demonstrated that the fluorescent partitioning tracer was able to
      detect and quantify the presence of NAPL at low flow rates. At larger flow rates
      and/or higher NAPL saturations, the tracer increasingly underpredicted the NAPL
      volume as expected and this is attributed primarily to non-equilibrium
      partitioning. Despite little change in permeability, change in NAPL saturations
      from 4% to 8% resulted in significant NAPL saturation underestimates at the same
      flow rates implying coalescence of NAPL into wider separated but larger ganglia.
      A 2-D investigation of an idealised heterogeneous residual NAPL contaminated flow
      field indicated little permeability change in the NAPL contaminated zone and thus
      little flow bypassing, leading to reduced underpredictions of NAPL saturations
      than for equivalent quasi 1-D cases. This was attributed to increased 'sampling'
      of the NAPL by the tracer. The process is clearly visually identifiable from the
      experimental images. This rapid and relatively inexpensive experimental method is
      of value in laboratory studies of partitioning tracer behaviour in porous media;
      in particular, the ability to observe full field concentrations makes it valuable
      for the study of complex heterogeneous systems.

PMID- 16298416
TI  - Quantifying the uncertainty of on-line sensors at WWTPs during field operation.
AB  - It remains an ongoing task to quantify the uncertainty of continuous measuring
      systems at WWTPs during field operation. The commonly used methods are based on
      lab experiments under standardized conditions and are only suitable for
      characterizing the measuring device itself. For measuring devices under field
      conditions, a knowledge of the response time, trueness and precision is equally
      important. A method is proposed which can be used to characterize newly installed
      on-line sensors or to evaluate monitoring data which may contain systematic
      errors. The concept is based on comparative measurements between the sensor and a
      reference. A linear regression is used to differentiate between trueness and
      precision. Various statistical tests are conducted to validate the preconditions
      of linear regression. The information about the trueness and precision of the
      measuring system under field conditions helps to adapt control strategies more
      effectively to the relevant processes and permits sophisticated control concepts.
      Moreover, the concept can help to define guidelines for evaluating the
      uncertainties of effluent quality monitoring to overcome the concerns about on
      line sensors, improve the trust in these systems and to allow the use of
      continuously measuring systems for legislative purposes. The approach is
      discussed in detail in this paper and all statistical tests and formulas are
      listed in the Appendix.

PMID- 16298417
TI  - Virus removal by iron coagulation-microfiltration.
AB  - This study was undertaken to determine virus removal efficiency by iron
      coagulation followed by microfiltration (MF) in water treatment using the MS2
      bacteriophage (approximately 25 nm diameter) as a tracer virus. Results from
      these bench-scale studies were used to propose a mechanism for virus removal by
      iron coagulation-MF. Ferric chloride was used as coagulant, and the dosages were
      0, 2, 5, and 10 mg/L as Fe(III) with pH adjusted during mixing to 6.3, 7.3 and
      8.3. In the absence of iron-coagulation and with less than 2 mg/L Fe, MF alone
      achieved less than a 0.5 log removal of MS2 virus. However, iron-coagulation
      pretreatment dramatically improved virus removal, especially in the 5-10 mg/L Fe
      dose range, ultimately achieving more than 4-log removal at pH 6.3 with 10-mg/L
      Fe dose. For the 5 and 10 mg/L Fe dosages, decreasing pH in the 8.3-6.3 range
      resulted in significantly greater virus removal. For 0 and 2 mg/L iron dosages,
      decreasing pH in the 8.3-6.3 range also improved virus removal, but to a lesser
      extent. The experimental data indicates negatively charged MS2 viruses first
      adsorbed onto the positively charged iron oxyhydroxide floc particles before
      being removed by MF. MS2 viruses were not inactivated in iron or aluminum
      coagulation as evidenced by the fact that their concentrations before and after
      coagulation, settling, and re-suspension of the coagulated sludge were not
      statistically different.

PMID- 16298418
TI  - Changes in acetylator phenotype over the lifespan in the Wistar rat.
AB  - Acetylation capacity during drug metabolism differs between species, gender and
      age groups. OBJECTIVE: The purpose of this work was to determine variations in
      the acetylating phenotype (AP), in a longitudinal study, as a function of growth
      and development. METHODS: Twenty male Wistar rats were studied. AP was determined
      on days 21, 48, 114, 180, 457 and 780 with oral doses of 30mg/kg of sulphadiazine
      (SDZ) by urine collection. The Schroeder and Vree methods were used to obtain SDZ
      concentrations, both acetylated and not acetylated. Rats were classified as slow
      or fast acetylators in accordance with previously validated metabolic indicators.
      RESULTS: Of the 20 rats phenotyped at 21 and 48 days of age, 18 were slow and 2
      were fast acetylators. As age and consequent growth progressed, changes in the
      expression of AP were registered. At 114 days, 16 rats were slow and 4 were fast
      acetylators; at 180 days, 12 were slow and 8 were fast; at 457 days, 6 were slow
      and 14 were fast; at 780 days, the 20 rats were fast acetylators. Slow
      acetylation predominates at younger ages. CONCLUSIONS: The effect of growth and
      developmental progress on AP is evident and relates to previous reports of
      changes in AP, determined by age in animal and human models. The relevance of
      changes determined by growth and development should be considered in rational
      drug management.

PMID- 16298419
TI  - Organic air pollutants inside and outside residences in Shimizu, Japan: levels,
      sources and risks.
AB  - Concentrations of 38 organic air pollutants including aromatic hydrocarbons
      (AHCs), carbonyl compounds (CCs), volatile organic halogenated compounds (VOHCs),
      and organophosphorus compounds (OPCs) were measured in indoor and outdoor air in
      an industrial city, Shimizu, Shizuoka Prefecture, Japan. Levels of pollutants
      tended to be higher indoors than outdoors in both summer and winter except for
      benzene, carbon tetrachloride, trichloroethylene, tetrachloroethylene, and
      dichlorvos (DDVP). This trend was especially pronounced for CCs such as
      formaldehyde and acetaldehyde. For the organic air pollutants, the concentrations
      of AHCs and VOHCs substantially increased in winter, but not those of CCs and
      OPCs; the trends were similar for both indoors and outdoors. We investigated
      possible indoor sources of pollutants statistically. Multiple regression analysis
      of corresponding indoor and outdoor concentrations and the responses to our
      questionnaire showed that indoor concentrations of certain AHCs were
      significantly affected by their outdoor concentrations and cigarette smoking. For
      formaldehyde, indoor concentrations were significantly affected by house age and
      the presence of carpet or pets. For p-dichlorobenzene (pDCB), the concentrations
      in bedroom trended to be higher than those in other indoors and outdoors,
      suggested that mothballs for clothes present in bedrooms are the principal indoor
      source of pDCB. We compared indoor and outdoor pollutant concentrations to
      acceptable risk limits for 11 organic air pollutants. In indoors without smoking
      samples, the geometric mean concentrations of benzene, formaldehyde,
      acetaldehyde, carbon tetrachloride, pDCB, and DDVP exceeded the equivalent
      concentration representing the upper bound of one-in-one-hundred-thousand (1x10(
      5)) excess risk over a lifetime of exposure.

PMID- 16298420
TI  - Effects of different aspirin formulations on platelet aggregation times and on
      plasma salicylate concentrations.
AB  - BACKGROUND: Early aspirin treatment is widely used to inhibit platelet activity
      and to reduce morbidity and mortality in patients presenting with an acute
      myocardial infarction or a stroke. A number of different aspirin formulations
      have been used for this purpose; however, a comparison of their effectiveness in
      inhibiting early platelet aggregation has not been determined. METHODS: In this
      study, we determined plasma salicylate concentrations and platelet inhibitory
      activities at various times after ingestion of three commonly used aspirin
      formulations: soluble aspirin (Alka-Seltzer), 325 mg, chewed baby aspirin, 324
      mg, and whole compressed non-enteric coated aspirin, 324 mg. Twenty-four healthy
      volunteers, 18-39 years of age, participated in the prospective single-blinded
      triple-crossover study. Plasma salicylate concentrations and inhibition of
      arachidonic acid-induced platelet aggregation were determined on post-dose blood
      samples collected at 2.5, 5.0, 7.5, 10, 15, 20, 25, 30, and 40 min. All subjects
      crossed over to the other two formulations with at least 2 weeks between
      ingestions. RESULTS: The median platelet inhibition times for the chewed,
      soluble, and whole aspirin formulations were 7.5, 7.5, and 10.0 min,
      respectively. Soluble and chewed aspirin were found to inhibit platelet
      aggregation faster than whole aspirin (p<0.001); however, there were no
      significant differences in platelet aggregation times between the soluble and
      chewed formulations (p<0.163). Inhibition of platelet aggregation was found to
      occur at an average plasma salicylate concentration of 2.46 microg/mL, regardless
      of method of ingestion. CONCLUSION: The results indicate that soluble and chewed
      aspirin inhibit platelet aggregation in a shorter period of time than does whole
      aspirin. The results suggest that chewing baby aspirin or taking soluble buffered
      aspirin may be the preferred route of administration for early platelet
      inhibition.

PMID- 16298421
TI  - Primary insular carcinoid of the ovary.
AB  - BACKGROUND: Primary insular carcinoid tumor of the ovary is a rare tumor and
      accounts for fewer than 1% of all cases of carcinoid in the body. With the
      exception of a single reported case, all previously described functioning ovarian
      carcinoid tumors have measured at least 10 cm in diameter. Thus, there appears to
      be a good correlation between the size of the tumor and the presence of the
      carcinoid syndrome. CASE REPORT: We describe a case of a functioning primary
      insular carcinoid tumor of the ovary measuring just 6 cm in maximal diameter.
      CONCLUSION: Although primary ovarian carcinoid tumor is very rare, a high
      clinical index of suspicion must be maintained, especially in a patient
      presenting with carcinoid syndrome and a small adnexal mass.

PMID- 16298422
TI  - The safety and efficacy of the weekly dosing of irinotecan for platinum- and
      taxanes-resistant epithelial ovarian cancer.
AB  - OBJECTIVE: Irinotecan is one of the drugs that might be effective against
      platinum- and taxanes-resistant epithelial ovarian cancer. We investigated
      efficacy and safety of the weekly dosing schedule of irinotecan. METHODS: From
      September 2001 to March 2003, 28 eligible patients who have histologically
      confirmed epithelial ovarian cancer, which was resistant or refractory to both
      platinum and taxanes, were consecutively treated at the National Cancer Center
      Hospital. Irinotecan (100 mg/m(2)) was administered intravenously over 90 min on
      days 1, 8, and 15. The chemotherapy was repeated every 4 weeks, up to 6 cycles.
      RESULTS: A total of 107 treatment cycles of irinotecan were administered to 28
      patients. The median number of prior chemotherapy regimen was 3. Among 28
      patients, 8 (29%) responded to irinotecan (2 complete responses and 6 partial
      responses). The median time to progression was 17 weeks. Three patients
      experienced hematological toxicities of Grade 4. Five patients experienced non
      hematological toxicities Grade 3 or 4. No treatment-related death occurred.
      CONCLUSION: The weekly dosing schedule of irinotecan seems to be effective and
      safe salvage chemotherapy regimen for platinum- and taxanes-resistant or
      refractory epithelial ovarian cancer. Gastrointestinal toxicities, especially
      diarrhea, were moderate and manageable in an outpatient setting.

PMID- 16298425
TI  - Combined effect of DHA and alpha-tocopherol enrichment on sperm quality and
      fertility in the turkey.
AB  - The aim of the present study was to characterize the dietary effects of n-3 LC
      PUFA and alpha-tocopheryl acetate (vE) on the quality, phospholipid fatty acid
      composition, alpha-tocopherol content (alpha-T) and in vitro susceptibility to
      lipid peroxidation in turkey semen. Fertility of fresh semen was also evaluated.
      Male turkeys were randomly divided and fed either a control diet or a fish oil
      and vE rich diet (FO diet) from 40 to 60 weeks of age. The FO diet increased the
      proportion of n-3 fatty acids in spermatozoa and as a consequence the (n-3)/(n-6)
      ratio also increased. These changes did not affect the proportion of n-9 PUFAs,
      particularly of C22:3n-9, in semen. The sperm content of alpha-T was dependent by
      the dietary supplementation of the vitamin and the sperm content was more than
      doubled supplying 120 mg kg(-1) of feed to the males compared to the 60 mg kg(-1)
      of feed in the control diet. In agreement with the major content of alpha-T in
      spermatozoa collected from the FO group were significantly less susceptible to in
      vitro induced oxidation. The reproductive capacity of the male breeders was not
      affected by the diet; however the result is considered of some relevance for
      field conditions where even very small changes have economic interest being
      applied to large bird population.

PMID- 16298423
TI  - 2-Phenylethylamine in combination with l-deprenyl lowers the striatal level of
      dopamine and prolongs the duration of the stereotypy in mice.
AB  - 2-Phenylethylamine (PEA)-induced stereotypy in rodents is suggested to model
      psychotic symptoms of schizophrenia. It is reported that PEA induces dopamine
      release in the striatum in vivo and in vitro. The present study analyzed the PEA
      induced stereotypy and possible associated brain dopamine metabolism in mice.
      Using male ICR mice treated with a combination of PEA (100 mg/kg, i.p.) and
      increasing doses of l-deprenyl (0-10 mg/kg, s.c.), we examined (1) the behavioral
      profile of stereotypy (rating the scores), and (2) the tissue levels of dopamine
      and its metabolites by high-performance liquid chromatography. The stereotypic
      scores reached a plateau level at 10 min which lasted until 30 min after a single
      administration of 100 mg/kg PEA. The stereotyped behavior completely disappeared
      45 min after PEA administration. Pretreatment with l-deprenyl (0.1, 1, and 10
      mg/kg, s.c.) dose-dependently prolonged the duration of PEA-induced stereotypy.
      Notably, pretreatment with l-deprenyl dose-dependently increased the continuous
      sniffing. Treatment with PEA in combination of l-deprenyl (1 and 10 mg/kg)
      significantly reduced the level of dopamine in the region of the striatum and
      nucleus accumbens, compared with control animals. These results suggest that PEA
      in combination with l-deprenyl prolonged the duration of the stereotypy
      (particularly, continuous sniffing) while reducing the striatal level of
      dopamine.

PMID- 16298426
TI  - Functional MRI of conventional and anomalous metaphors in Mandarin Chinese.
AB  - This study looks at whether conventional and anomalous metaphors are processed in
      different locations in the brain while being read when compared with a literal
      condition in Mandarin Chinese. We find that conventional metaphors differ from
      the literal condition with a slight amount of increased activation in the right
      inferior temporal gyrus. In addition, when the anomalous metaphor condition is
      compared with the literal condition, increased activation occurs bilaterally in
      the frontal and temporal gyri. Lastly, the comparison between the anomalous and
      conventional metaphor conditions shows bilateral activation in the middle frontal
      gyrus and the precentral gyrus, and right-hemisphere activation in the superior
      frontal gyrus. Left hemisphere activation is found in the inferior frontal gyrus
      and fusiform gyrus. The left hemisphere activation in the frontal and temporal
      gyri point to the recruitment of traditional language-based areas for anomalous
      metaphor sentences, while the right-hemisphere activation found suggests that
      remote associations are being formed. In short, our study supports the idea that
      metaphors are not a homogenous type of figurative language and that
      distinguishing between different types of metaphors will advance theories of
      language comprehension.

PMID- 16298427
TI  - Brain activation during the course of sentence comprehension.
AB  - The purpose of this study is to determine, by functional magnetic resonance
      imaging, how the activated regions of the brain change as a Japanese sentence is
      presented in a grammatically correct order. In this study, we presented
      constituents of a sentence to Japanese participants one by one at regular
      intervals. The results showed that the left lingual gyrus was significantly
      activated at the beginning of the sentence, then the left inferior frontal gyrus
      and left supplementary motor area, in the middle of the sentence, and the left
      inferior temporal gyrus, at the end of the sentence. We suggest that these brain
      areas are involved in sentence comprehension in this temporal order.

PMID- 16298428
TI  - Socio-demographic and clinical predictors of quality of life in patients with
      schizophrenia or schizo-affective disorder.
AB  - This article discusses the relationships between socio-demographic, clinical
      characteristics and Quality of Life (QOL) of individuals with schizophrenia. The
      client version of the Canadian version of the Wisconsin Quality of Life Index
      (CaW-QLI) was used with a population of 182 individuals with either schizophrenia
      or schizo-affective disorder. Multivariate analyses of variance with Tukey post
      hoc tests were used to assess differences between groups defined according to
      socio-demographic and clinical characteristics on all sub-scale scores in
      addition to the global score on the CaW-QLI. Relationships between socio
      demographic characteristics and QOL were found for gender, age, education,
      employment status and living arrangement. Differences in QOL were found between
      groups with different clinical characteristics, such as diagnosis,
      hospitalization during the last 12 months and age at first hospitalization. Using
      socio-demographic and clinical variables in addition to psychosocial variables
      appears to be promising for understanding QOL in psychotic patients.
      Methodological considerations for future research are discussed.

PMID- 16298430
TI  - Broad spectrum antimicrobial activity of leukocyte extracts from the American
      alligator (Alligator mississippiensis).
AB  - Leukocytes were isolated from whole blood of wild alligators by differential
      sedimentation. The leukocytes were disrupted in 5% AcOH and the crude extracts
      processed by ultrafiltration. The extracts were subjected to solvent exchange
      (0.1% AcOH) and the fraction that contained macromolecules between 1 and 10 kDa
      were subjected to further analyses. The acid extracts of the alligator leukocytes
      exhibited substantial antimycotic activities against six of eight species of
      Candida yeast tested. In addition, the alligator leukocyte extracts were
      effective as antimicrobial agents against 10 of 12 bacterial species, and
      displayed moderate activity against two enveloped viruses (human immunodeficiency
      virus-1 and herpes simplex virus-1(HF)). Kinetic analyses revealed that the
      antimycotic effects of the leukocyte extract occurred rapidly, with 64% fungal
      growth inhibition within 3 min of exposure. The molecule(s) responsible for the
      antimicrobial activities were sensitive to proteases, heat-stable, acid soluble,
      and in the 1-10 kDa range. These data suggest that alligator leukocytes express
      cationic peptides that are responsible for their antimicrobial properties.

PMID- 16298429
TI  - Transsexual subtypes: clinical and theoretical significance.
AB  - The present study was designed to investigate whether transsexuals can be validly
      subdivided into subtypes on the basis of sexual orientation, and whether
      differences between subtypes of transsexuals are similar for male-to-female (MF)
      and female-to-male transsexuals (FMs). Within a large transsexual sample (n=187),
      homosexual and nonhomosexual subjects were compared on a number of
      characteristics before the start of treatment. Differences within MF and FM
      groups were also investigated. Homosexual transsexuals were found to be younger
      when applying for sex reassignment, reported a stronger cross-gender identity in
      childhood, had a more convincing cross-gender appearance, and functioned
      psychologically better than nonhomosexual transsexuals. Moreover, a lower
      percentage of the homosexual transsexuals reported being (or having been) married
      and sexually aroused while cross-dressing. The pattern of findings was different
      for MFs and FMs. No differences between homosexuals and nonhomosexuals were found
      in height, weight, or body mass index. A distinction between subtypes of
      transsexuals on the basis of sexual orientation seems theoretically and
      clinically meaningful. The results support the notion that in the two groups
      different factors influence the decision to apply for sex reassignment. The more
      vulnerable nonhomosexual transsexuals may particularly benefit from additional
      professional guidance before and/or during treatment.

PMID- 16298431
TI  - Immunization of susceptible mice with gp43-pulsed dendritic cells induce an
      increase of pulmonary Paracoccidioidomycosis.
AB  - The development of the appropriate CD4 Th subset is important for disease
      resolution and several studies have shown that different outcomes of a disease
      can be obtained by influencing the commitment of precursors to either, Th1 or Th2
      lineage. Dendritic cells (DCs) are able to initiate response in naive T cells and
      they also participate in Th cell education. In the present study we demonstrated
      that purified gp43 lead to down-regulation of MHC-II and adhesion properties of
      immature DCs and in LPS-induced DCs maturation. It was also shown that purified
      gp43 from Paracoccidioides brasiliensis has the same inhibitory effect on IL-12
      release. Mice infected with Paracoccidioides brasiliensis that received DCs plus
      gp43 plus LPS had a significant increase of the lung colony forming units when
      compared with control (not immunized) or those that received only DCs plus LPS.
      Thus, the granuloma morphology seen in immunized mice was different when compared
      with non-immunized controls. These data suggest that gp43 affects many functions
      of the host cells, indicating that these alterations might be used by
      Paracoccidioides brasiliensis to reduce the effectiveness of the immune response
      thus facilitating the establishment and fate of primary infection in susceptible
      host.

PMID- 16298432
TI  - Clonotypic analysis of cerebrospinal fluid T cells during disease exacerbation
      and remission in a patient with multiple sclerosis.
AB  - Migration of autoreactive T cells into the central nervous system (CNS)
      compartment is thought to be an important step in the pathogenesis of multiple
      sclerosis (MS). To follow the evolution of T cell repertoire in the CNS of a
      patient with relapsing-remitting MS, we analyzed cerebrospinal fluid (CSF) cells
      obtained during an acute clinical exacerbation, and subsequent disease remission
      after 13 months of immunomodulatory therapy. T cell receptor CDR3 region length
      distribution was significantly altered during the relapse, demonstrating the
      presence of clonally expanded T cells in the CSF. CDR3 spectratyping is a
      valuable approach to identify disease-associated T cells in the CNS.

PMID- 16298433
TI  - Overcoming failure to repair demyelination in EAE: an important step towards
      neuroprotection in multiple sclerosis.

PMID- 16298434
TI  - Management of incidental thyroglossal duct cysts during laryngotracheal
      reconstruction.
AB  - Thyroglossal duct cysts originate from trapped elements of the thyroglossal duct
      tract during embryological descent of the thyroid gland. The incidental finding
      of a thyroglossal duct cyst during cervical surgery has not been described
      previously. We present four cases of small asymptomatic thyroglossal duct cysts
      discovered as an incidental finding during laryngotracheal reconstruction. In
      each case, the cyst was removed using a Sistrunk procedure. In all four cases the
      patient was successfully decannulated, and there were no cases of cyst
      recurrence. We also consider the implications that these four cases may have on
      the perceived incidence of the thyroglossal duct cysts and their management.

PMID- 16298436
TI  - Eye use during viewing a reflection: behavioural lateralisation in zebrafish
      larvae.
AB  - Development of visual lateralisation was studied in zebrafish larvae of an
      outbred strain when examining their own reflection in a mirror. There was
      significant left eye preference at all ages studied. A decrease in left eye use
      around 14 days, followed by a later increase at 21 days, parallels similar but
      differently timed shifts in the domestic chick. Age-dependent shifts in the
      likelihood of control by one or other eye system may be responsible. Larvae
      tested at 26 days of age with unfamiliar conspecifics of similar age also used
      the left eye (LE). Larvae of another strain (TupLF) also LE viewing of their
      reflection, although this was confined to the first or first and second minutes
      of the test rather than lasting through 10 min. The reflection differs from prior
      experience of fellows in the timing and character of its movements relative to
      those of the larva. Specialisation of the left eye system for the assessment of
      novelty, which is present in zebrafish, just as in many other vertebrates,
      probably therefore explains left eye use in the mirror test. Reasons why strains
      might differ in the length of time that they devote to assessment of the
      reflection are discussed.

PMID- 16298435
TI  - Engineering the genome of Grapevine virus A into a vector for expression of
      proteins in herbaceous plants.
AB  - Grapevine virus A (GVA), a species of the genus Vitivirus, consists of a
      approximately 7.4 kb single-stranded RNA genome of positive polarity, organized
      into five open reading frames (ORFs). In addition to grape varieties, GVA infects
      Nicotiana benthamiana plants and protoplasts. We engineered the genome of GVA as
      a vector that includes duplication of homologous sequences that contain the
      promoter of the movement protein (MP) sgRNA, supplemented by enzymatic
      restriction sites to be used as a convenient tool for transient expression of
      foreign genes from an individual sgRNA. The resulting vector was able to infect
      and to move in N. benthamiana plants in a manner similar to the wild-type GVA,
      but it was not stable and the inserted sequence was lost from the genome.
      Replacing the duplicated promoter with a GVA-MP promoter derived from a distantly
      related isolate of GVA improved the stability of the inserted sequence. The
      resulting vector was successfully used to express the reporter gene beta
      glucuronidase (GUS) and the coat protein gene of Citrus tristeza virus in
      inoculated N. benthamiana plants. Development of a useful GVA vector is expected
      to find a use as a biotechnological tool for improvement of grapevines and it may
      enable vine breeders to bypass obstacles involved in genetic manipulation of
      perennial and fruiting plants.

PMID- 16298437
TI  - Dietary copper exposure and recovery in Nile tilapia, Oreochromis niloticus.
AB  - There are few reports of dietary copper (Cu) toxicity to warm water species of
      freshwater fish, and little is known about recovery from dietary Cu exposure. In
      this study Nile tilapia (Oreochromis niloticus) were fed to satiation on a Cu
      loaded diet (2000 mg Cu kg(-1)dry weight (dw) feed), or a control diet (3 mg Cu
      kg(-1)dw feed), for 42 days. All fish were then fed the control diet for a
      further 21 days to assess recovery. Nutritional performance, haematology,
      histology, and tissue ion content (Cu, Na(+), and K(+)) were measured. No
      mortalities occurred during the experiment. Dietary copper exposure was confirmed
      by elevated Cu concentrations in the intestine (30-fold), liver (three-fold) and
      gills (2.7-fold) of Cu-exposed fish compared to controls after 42 days (ANOVA, P
      < 0.05). Copper-exposed fish showed a reduction in food intake, and weight gain
      by day 21 of exposure, compared to controls (ANOVA, P < 0.05) and this persisted
      throughout the experiment. There were no treatment-dependent effects on food
      conversion ratio or hepatosomatic index, and all fish showed normal tissue Na(+)
      and K(+), and haematology throughout the experiment. Gill and intestine did not
      show overt pathology, but fatty change was observed in the liver of Cu-fed fish
      during exposure. The recovery phase on normal food was characterised by a
      reduction in intestinal and branchial Cu levels back to control values. However,
      the liver of the Cu-fed fish showed a further 1.7-fold rise in Cu content and
      marked hepatic lipidosis (increased intracellular fat stores) post-exposure,
      suggesting redistribution of Cu to the liver and delayed hepatotoxicity.

PMID- 16298438
TI  - Maternal nutritional state determines the sensitivity of Daphnia magna offspring
      to short-term Fenvalerate exposure.
AB  - Daphnia populations in the field suffer periodic natural stress conditions such
      as low food levels. It is known that at low nutritional supply, Daphnia produces
      fewer but larger offspring, which are acutely less sensitive to chemical stress.
      We hypothesized that the change in the reproductive strategy may also alter the
      chronic sensitivity of offspring to pesticides, which usually occur in the field
      in a pulsed manner. We therefore investigated the influence of maternal food
      quantity of Daphnia magna on (1) offspring size and successive performance and
      (2) sensitivity to a 24-h exposure to the pyrethroid insecticide Fenvalerate.
      Daphnia cultures were maintained at a high and low food level. Produced offspring
      were subsequently used in life-table response experiments, which were performed
      under low food conditions. Results showed that low maternal food conditions
      (compared to high) increased the offspring size at time of birth, reduced age at
      first reproduction and increased reproductive output, which jointly enhanced
      offspring fitness as estimated by the population growth rate (r). Fenvalerate
      exposure in combination with low maternal food levels caused (compared to high) a
      strong decrease in acute sensitivity of neonates, which was generally also
      observed for chronic endpoints. Hence, reduction in population growth rate
      resulting from short-term pesticide exposure appeared to be less strong when
      compared to daphnids originating from high fed mothers. Our findings illustrate
      the importance of considering more environmentally relevant conditions (i.e. low
      maternal food level, short-term exposure) when linking effects observed in
      laboratory tests to potential risks in the field.

PMID- 16298439
TI  - Conservation of the vaccine antigen gene, TSOL18, among genetically variant
      isolates of Taenia solium.

PMID- 16298440
TI  - Molecular characterization of the insulin-like growth factor-I (IGF-I) gene in
      channel catfish (Ictalurus punctatus).
AB  - The insulin-like growth factor I (IGF-I) gene was characterized in channel
      catfish. Partial cDNA sequence, missing exon 1 and part of exon 2, was obtained
      in 5'- and 3'-RACE experiments. Direct sequencing of two bacterial artificial
      chromosome clones revealed gene structure and provided sequence from 640 bp
      upstream of the initiator methionine to 136 bp beyond the polyadenylation site.
      Genomic sequence contained a putative TATA box 506 bp upstream of the initiator
      methionine. The 477-bp reading frame within five exons encoded a 159-amino acid
      (aa) pre-propeptide highly similar to IGF-I in higher vertebrates. The sequence
      encoding the signal peptide was unique in catfish and contained 70% G+C content
      with the potential for a stable stem-loop structure. Full-length cDNA was only
      maintained in recombination-deficient (DH10B) strain E. coli. Levels of IGF-I
      mRNA were highest in liver, followed by brain and muscle, then heart and kidney
      (P<0.05). A CT/GA dinucleotide microsatellite in intron 1 was highly polymorphic
      in commercial channel catfish, and permitted placement of the IGF-I gene on the
      catfish genetic map. However, specific IGF-I alleles were not correlated with
      differences in growth rate from 100 to 130 days post-hatch in USDA103 line
      catfish.

PMID- 16298441
TI  - Hypertension is an independent risk factor for contrast nephropathy after
      percutaneous coronary intervention.
AB  - BACKGROUND: The administration of radiographic contrast agents is an important
      cause of acute renal failure. We hypothesised that hypertension is an independent
      risk factor for the development of contrast nephropathy in patients undergoing
      percutaneous coronary intervention. METHODS: 1383 consecutive patients scheduled
      for elective or emergency percutaneous coronary intervention were randomly
      assigned to receive isotonic or half-isotonic hydration. Contrast nephropathy was
      defined as a rise in serum creatinine of at least 44 micromol/l (0.5 mg/dl)
      within 48 h of the procedure. Hypertension was defined as self-reported history
      of treated or untreated diagnosed high blood pressure. RESULTS: The prevalence of
      hypertension was 63%. Patients with hypertension were significantly older, were
      more often female, smoked less and had a higher incidence of 3-vessel disease
      than patients without hypertension. The estimated glomerular filtration rate was
      slightly lower in hypertensive patients. There was no difference in preventive
      hydration regimen, type and quantity of contrast medium used, or quantity of
      intravenous fluids given. Contrast nephropathy developed in 17 of 874
      hypertensive patients (2%) compared to 2 of 509 patients (0.4%) without
      hypertension (p = 0.016). When contrast nephropathy was defined as a 25% rise in
      baseline creatinine, the disease developed in 103 patients (12%) with and 36
      patients (7%) without hypertension (p = 0.005). After adjustment for confounders,
      arterial hypertension remained an independent predictor of contrast nephropathy
      (odds ratio 4.6, 95% CI 1.0-20.5, p = 0.046). CONCLUSION: Hypertension is an
      independent risk factor for the development of contrast nephropathy. Further
      preventive strategies to lower the incidence of contrast nephropathy in
      hypertensive patients are warranted.

PMID- 16298442
TI  - A successful stenting of the coarctation of aorta in a patient presented with
      acute pulmonary edema.
AB  - A 64-year-old female patient presented with heart failure with acute pulmonary
      edema due to severe aortic coarctation. After endotracheal intubation, aortogram
      was performed and revealed a severe luminal narrowing in the distal thoracic
      aorta with a peak systolic pressure gradient of 100 mm Hg across the lesion.
      Stent implantation was performed with 24*100 mm self-expandable Nitinol-S stent
      after predilation with 10*40 mm balloon. After stenting, the patient's symptom
      and sign of congestive heart failure were remarkably improved and able to remove
      endotracheal intubation tube, with no significant adverse cardiac events observed
      during a 1-year clinical follow-up.

PMID- 16298443
TI  - Positive family history of coronary artery disease is associated with reduced
      myocardial vasoreactivity in healthy men.
AB  - OBJECTIVE: Positive family history as a risk factor for coronary artery disease
      seems to be most important in subjects who otherwise are at low risk. We examined
      the association between family history of coronary artery disease and myocardial
      vasoreactivity in healthy men. METHODS: 35 non-smoking healthy men (age 35+/-7
      years) were studied: 16 had positive family history of coronary artery disease
      and 19 had negative family history. The myocardial blood flow measurements were
      performed basally and during adenosine infusion (140 mug/kg/min) with and without
      simultaneous physiological hyperinsulinemia (insulin infusion at a rate of 1
      mU/kg/min) using positron emission tomography and O-15-water. RESULTS: Basal
      myocardial blood flow was similar between the subjects with positive and negative
      family history of coronary artery disease (0.79+/-0.19 and 0.79+/-0.21 mL g(-1)
      min(-1), NS). Adenosine stimulated flow was significantly reduced in subjects
      with positive family history (3.0+/-0.5 vs 4.0+/-1.2 mL g(-1) min(-1),
      respectively, p=0.003). During physiological hyperinsulinemia adenosine
      stimulated flow was further enhanced in both groups but significantly blunted in
      subjects with positive family history (3.7+/-0.9 vs 5.2+/-1.5 mL g(-1) min(-1),
      respectively, p=0.001). These differences remained significant after simultaneous
      controlling for age, BMI, HbA1c, LDL-cholesterol, HDL-cholesterol and blood
      pressure (p=0.002). CONCLUSIONS: Healthy non-smoking men with positive family
      history of coronary artery disease are characterized by impaired myocardial
      vasoreactivity.

PMID- 16298444
TI  - Retrospective ECG-gated left ventriculography using multislice CT following left
      ventricular bolus injection and evaluation of its utility and motion artifact at
      every cardiac phase.
AB  - Following left ventricular bolus injection of contrast material, multislice CT
      scanning was performed. With retrospective ECG-gated reconstruction, we could
      acquire volume data for the heart at any cardiac phase and selectively depict
      only the left ventricle and aorta with maximum intensity projection. Temporal
      resolution of multislice CT was not sufficient to eliminate motion artifact
      except just before atrial contraction periods.

PMID- 16298445
TI  - Application of hammerhead ribozymes in filamentous fungi.
AB  - Metabolic engineering in filamentous fungi is a emerging field of research as
      many fungi produce high value primary and secondary metabolites. Ribozyme
      technology can be used as a tool for metabolic engineering to influence metabolic
      pathways and to knock down the expression of specific genes of interest.
      Hammerhead ribozymes can target virtually any mRNA sequence of choice and prevent
      gene expression on the post-transcriptional level. They are thus a versatile tool
      for timed and spatial elimination of unwanted gene products. As current research
      has only investigated the application of ribozymes in bacteria, yeast and
      mammalian cells, we decided to carry out a study on whether this technology can
      also function with filamentous fungi. We employed a sensitive, quantitative
      reporter-based model system as a proof of concept, using the Escherichia coli
      beta-glucuronidase transcript (uidA) as the target mRNA and Aspergillus giganteus
      as the host. This system was used to validate the in vivo activities of seven
      different hammerhead ribozymes, which were selected by in silico analysis of the
      uidA mRNA. All ribozymes tested were able to reduce the reporter activity up to a
      maximum of 100%, demonstrating that ribozyme technology is indeed a useful tool
      in fungal metabolic engineering.

PMID- 16298446
TI  - Directed evolution of metabolic pathways.
AB  - The modification of cellular metabolism is of biotechnological and commercial
      significance because naturally occurring metabolic pathways are the source of
      diverse compounds used in fields ranging from medicine to bioremediation.
      Directed evolution is the experimental improvement of biocatalysts or cellular
      properties through iterative genetic diversification and selection procedures.
      The creation of novel metabolic functions without disrupting the balanced
      intracellular pool of metabolites is the primary challenge of pathway
      manipulation. The introduction of coordinated changes across multiple genetic
      elements, in conjunction with functional selection, presents an integrated
      approach for the modification of metabolism with benign physiological
      consequences. Directed evolution formats take advantage of the dynamic structures
      of genomes and genomic sub-structures and their ability to evolve in multiple
      directions in response to external stimuli. The elucidation, design and
      application of genome-restructuring mechanisms are key elements in the directed
      evolution of cellular metabolic pathways.

PMID- 16298447
TI  - Stem cells and their applications in skin-cell therapy.
AB  - Skin stem cell biology is a rapidly advancing field in the life sciences. There
      is increasing evidence that skin represents a larger reservoir for adult stem
      cells (including mesenchymal, hematopoietic and neural stem cells) than the
      epidermis. Given that skin is easily accessible and immune privileged, skin stem
      cells will not only provide hope for the functional repair of the skin itself but
      will also offer a potential source of adult stem cells for the cell-based therapy
      of injuries and diseases throughout the body. This article reviews the current
      status of research in this area and discusses the occurrence, plasticity and
      potential uses of skin stem cells.

PMID- 16298448
TI  - In vitro release of the mTOR inhibitor rapamycin from poly(ethylene glycol)-b
      poly(epsilon-caprolactone) micelles.
AB  - An injectable formulation of rapamycin was prepared using amphiphilic block co
      polymer micelles of poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG-PCL).
      Drug-loaded PEG-PCL micelles were prepared by a co-solvent extraction technique.
      Resulting PEG-PCL micelles were less than 100 nm in diameter and contained
      rapamycin at 7% to 10% weight and >1 mg/mL. PEG-PCL micelles released rapamycin
      over several days, t50% 31 h, with no burst release; however, physiological
      concentrations of serum albumin increased the release rate 3-fold. Alpha
      tocopherol, vitamin E, was co-incorporated into PEG-PCL micelles and increased
      the efficiency of rapamycin encapsulation. The addition of alpha-tocopherol also
      slowed the release of rapamycin from PEG-PCL micelles in the presence of serum
      albumin, t50% 39 h.

PMID- 16298449
TI  - [Feet insoles and knee osteoarthritis: evaluation of biomechanical and clinical
      effects from a literature review].
AB  - OBJECTIVE: To determine the biomechanical and clinical effectiveness of foot
      insoles in patients with knee osteoarthritis. MATERIALS AND METHODS: A systematic
      review of the literature (Medline, Pascal and Embase) using the MESH words knee,
      and insole and plantar orthosis for the biomechanical part and osteoarthritis,
      and insole and plantar orthosis for the clinical part. Clinical studies were
      classified by 2 independent readers using the Jadad scale. RESULTS: Two
      biomechanical theories were found: the adduction moment theory, which explains
      the effect of heel wedging, and articular chain theory, which explains the effect
      of lateral wedged insoles. The clinical effect was explained more by an anti
      algesic effect than an anatomic or functional effect: the treated group consumed
      fewer nonsteroidal anti-inflammatory drugs than the placebo group for up to 2
      years of treatment. Evidence is lacking because of methodological weakness and
      few clinical trials. The information on side effects is limited. DISCUSSION:
      Laterally wedged foot insoles are proposed for the treatment of knee medial
      compartment osteoarthritis. The clinical effect is probably limited, but the
      treatment may reduce the digestive and renal side effects of prolonged use of
      nonsteroidal anti-inflammatory drugs. Foot insoles could be recommended in
      clinical practice despite the lack of evidence in comparing the effectiveness of
      other therapeutics in knee osteoarthritis. CONCLUSION: Use of foot insoles is a
      nonpharmacologic treatment of osteoarthritis of the knee medial compartment.

PMID- 16298450
TI  - [About two big buttocks: an erysipelas with lymphoedema after pelvis surgery].
AB  - We report the case of a 58-year-old man with erysipelas of both buttocks
      secondary to lymphoedema after pelvis surgery for prostatic cancer and multiple
      vascular interventions for iliofemoral thrombosis. The diagnosis was based on
      clinical examination and lymphoscintigraphy. This location of lymphoedema,
      limited to the buttocks, is uncommon; lower limbs are usually affected. This
      location needs a specific curative and preventive treatment, including antibiotic
      therapy, lymphatic drainage and contention to abate the condition and prevent a
      relapse.

PMID- 16298453
TI  - Who is at risk for post-transplant lymphoproliferative disorders (PTLD) after
      liver transplantation?

PMID- 16298451
TI  - Brain natriuretic peptide and cardiac autonomic function in type 2 diabetic
      patients.
AB  - The present study tested the hypothesis that increased plasma brain natriuretic
      peptide (BNP) levels are related to cardiac autonomic dysfunction in type 2
      diabetic patients. A total of 32 consecutive Japanese patients with type 2
      diabetes were assigned to either a high-BNP (>or=18 pg/ml) group (n=12; age 57+/
      13 years, mean+/-S.D.) or a normal-BNP (<18 pg/ml) group (n=20; 59+/-10 years).
      No patient had any overt structural heart disease. Cardiac autonomic function was
      assessed by measurements of baroreflex sensitivity (BRS), heart rate variability
      (HRV) and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphic findings.
      BRS was lower (p<0.005) in the high-BNP group than in the normal-BNP group.
      However, the components of HRV, and the early and delayed myocardial uptake of
      (123)I-MIBG and percentage washout rate of (123)I-MIBG were not significantly
      different between the groups. The plasma level of BNP negatively correlated with
      BRS (r=0.35, p=0.049). These findings suggest that increased plasma BNP levels
      were related to cardiac reflex parasympathetic dysfunction in our Japanese type 2
      diabetic patients.

PMID- 16298452
TI  - Pamidronate induced anti-proliferative, apoptotic, and anti-migratory effects in
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: The small GTPase of Ras and Rho families are widely involved in
      human tumorgenesis and metastasis. It has recently been reported that pamidronate
      inhibits the mevalonate pathway, which is required for the prenylation of the
      small GTPase. We demonstrated a possible beneficial use of pamidronate in the
      treatment of hepatocellular carcinoma (HCC). METHODS: The effect of pamidronate
      on cell proliferation was analyzed with five hepatoma cell lines using MTT assay.
      Apoptosis was evaluated by staining with DAPI and a histon ELISA assay. A cell
      migration assay was performed using the Modified Boyden Chamber. To analyze anti
      proliferation effect of pamidronate in vivo, tumor volumes were monitored with
      the intraperitoneal injection of pamidronate after subcutaneous inoculation of
      PLC/PRF/5 cells into nude mice. RESULTS: Pamidronate inhibited cell growth for
      all hepatoma cell lines. The amount of membrane associated Ras and phosphorylated
      extracellular signal-regulated kinase 2 (ERK 2) were reduced after pamidronate
      treatment. Pamidronate increased apoptosis and cleavage of Caspase-3, and -9.
      Pamidronate suppressed membrane associated RhoA and cell motility. In vivo, tumor
      volumes were significantly suppressed by pamidronate at three weeks (P<0.03).
      CONCLUSIONS: We conclude that pamidronate has therapeutic potential in inducing
      anti-proliferative, apoptotic, and anti-migratory effects in HCC.

PMID- 16298454
TI  - Micro- and nanoparticulates.
AB  - OBJECTIVES: Pharmacotherapeutics has begun to play an increasingly important role
      in the management of patients with neovascular age-related macular degeneration
      (AMD). Because micro- and nano-particulates are currently being evaluated as a
      potential drug-delivery option for AMD patients, the purpose of this analysis was
      to describe how micro- and nano-particulates have been used experimentally and
      what their potential clinical applications may be. FINDINGS: Micro- and nano
      particulates have been used primarily on a pre-clinical basis as new drug
      delivery devices in experimental models of neovascular AMD. CONCLUSIONS: It is
      likely that micro- and nano-particulates will become an important component of
      targeted clinical pharmacotherapeutics in patients with neovascular AMD.

PMID- 16298455
TI  - Misuse of ANOVA with cumulative intakes.
AB  - Cumulative responses are important for the study of ingestive behavior. The total
      amounts consumed at several time points after experimental or control treatments
      are often analyzed using a mixed-model analysis of variance. The method used by
      some investigators to calculate the significance of this difference is invalid
      and may lead to serious errors of inference. Direct analysis of cumulative data
      can lead to grossly erroneous p-values for certain effects because data from
      early time points contribute disproportionately to the outcome. Analysis of
      uncumulated data yields the appropriate levels of significance and all of the
      same hypotheses can be tested.

PMID- 16298456
TI  - "Ugh! That's disgusting!": Identification of the characteristics of foods
      underlying rejections based on disgust.
AB  - Previous research has demonstrated that individuals' beliefs about the disgusting
      properties of foods play a central role in predicting willingness to eat novel
      foods of either animal or non-animal origin (Martins & Pliner, in press). The
      present study aimed to identify what characteristics of foods make individuals
      perceive them as disgusting. In this study, participants read a set of scenarios
      designed to depict potentially disgusting foods; participants in Sample 1 rated
      the perceived disgustingness of the foods while participants in Sample 2 rated
      the foods on a variety of attributes relevant to theoretical conceptions of
      disgust. Multidimensional scaling revealed two dimensions, aversive textural
      properties of the foods and reminders of livingness/animalness, that accounted
      for most of the variability in ratings of perceived disgustingness of the foods
      depicted in the scenarios. Implications for our current conceptualization of
      disgust are examined.

PMID- 16298457
TI  - School lunch menus and 11 to 12 year old children's food choice in three
      secondary schools in England-are the nutritional standards being met?
AB  - OBJECTIVES: To determine if the lunchtime food provided to schoolchildren adheres
      to nutritional standards and to examine the influence of children's food choice
      on nutrient intake at lunchtime. SUBJECTS/SETTING: Seventy-four children aged 11
      12 years were recruited from three secondary schools. The school populations
      spanned a spectrum of socio-economic deprivation. Lunchtime food and nutrient
      intake was assessed over a 5 day period. DESIGN: Cross-sectional study of menu
      composition and children's food choice in relation to nutrient intake. METHODS:
      Dietary recording was by an indirect weighing method of menu composition and
      nutrient intake over a 5 day period. Statistical analysis was carried out using
      general linear modelling techniques including: t-test, one-way ANOVA and ANCOVA.
      RESULTS: One school met the standards on food group provision. Intakes of total
      fat, saturated fatty acids and monounsaturated fatty acids were greater in boys.
      Intake of folate was greater in girls. There were between-school differences
      (independent of gender) for intake of fatty acids, starch, calcium and folate,
      with socio-economic deprivation associated with a lesser nutrient intake.
      Children could have chosen meals higher in calcium, iron, folate and zinc and
      lower in starch and fat, from the extensive cafeteria menu of between 26 and 42
      food. For some nutrients, providing 'healthier' food influences intake of those
      nutrients whilst for other nutrients, children's food choice predominates. The
      majority of children did not meet the recommended targets for lunchtime nutrient
      intake, especially for micronutrients. CONCLUSIONS: Food provision in two out of
      three schools did not meet government guidelines and socio-economic deprivation
      was associated with worse food provision. Children from deprived areas were more
      likely to choose those foods of limited nutritional value than those from more
      privileged backgrounds. The statutory nutritional standards on their own, without
      a pricing policy to encourage healthier food choice or restrictions in food
      choice towards less healthy food are unlikely to catalyse the dietary changes
      that are so needed to ensure improved nutrient intakes amongst schoolchildren in
      England.

PMID- 16298458
TI  - Cloning and characterization of a novel calcium channel toxin-like gene BmCa1
      from Chinese scorpion Mesobuthus martensii Karsch.
AB  - Many studies have been carried on peptides and genes encoding scorpion toxins
      from the venom of Mesobuthus martensii Karsch (synonym: Buthus martensii Karsch,
      BmK), such as Na+, K+ and Cl- channel modulators. In this study, a novel calcium
      channel toxin-like gene BmCa1 was isolated and characterized from the venom of
      Mesobuthus martensii Karsch. First, a partial cDNA sequence of the Ca2+ channel
      toxin-like gene was identified by random sequencing method from a venomous gland
      cDNA library of Mesobuthus martensii Karsch. The full-length sequence of BmCa1
      was then obtained by 5'RACE technique. The peptide deduced from BmCa1 precursor
      nucleotide sequence contains a 27-residue signal peptide and a 37-residue mature
      peptide. Although BmCa1 and other scorpion toxins are different at the gene and
      protein primary structure levels, BmCa1 has the same precursor nucleotide
      organization and cysteine arrangement as that of the first subfamily members of
      calcium channel scorpion toxins. Genomic DNA sequence of BmCa1 was also cloned by
      PCR. Sequence analysis showed that BmCa1 gene consists of three exons separated
      by two introns of 72 bp and 1076 bp in length, respectively. BmCa1 is the first
      calcium channel toxin-like gene cloned from the venom of Mesobuthus martensii
      Karsch and potentially represents a novel class of calcium channel toxins in
      scorpion venoms.

PMID- 16298459
TI  - [Carotid stenosis caused by calcification].

PMID- 16298460
TI  - Orbital fractures: ophthalmic or maxillofacial?

PMID- 16298461
TI  - Craniofacial development in children with unilateral cleft lip and palate.
AB  - Unilateral cleft lip and palate is the most common cleft in humans. We
      investigated the craniofacial morphology of Turkish children with unilateral
      complete cleft lip and palate who had operations to close the cleft lip when they
      were 3 months old and to close the palate at 12 months. They were not given
      orthopaedic or orthodontic treatment. We compared 42 patients with unilateral
      complete cleft lip and palate (UCCLP) with 45 control children without UCCLP at
      mean ages of 13 and 15 years. The children with UCCLP had considerable
      morphological deviations compared with the matched children without clefts. They
      had significantly shorter and more posteriorly positioned maxillas (p<0.01).
      There was also an increase in cranial base angle (p<0.05), mandibular plane and
      gonial angle (p<0.01). There was a reduction in the posterior facial height
      (p<0.05) and an increase in the anterior facial height (p<0.01). The profile of
      the soft tissue was more convex (p<0.001) and the upper lip was thinner than in
      the children in the control group (p<0.01), and their noses were relatively
      further backwards and downwards (p<0.01).

PMID- 16298462
TI  - Intra-articular ramus ostectomy combined with costochondral grafting for the
      treatment of recurrent ankylosis of the mandible.
AB  - PURPOSE: This report seeks to demonstrate a technique for treating recurrent
      ankylosis of the mandible by creating a functional false joint at a level distal
      to the original joint. PATIENTS AND METHODS: This is a retrospective study
      involving patients treated between 1999 and 2003. Under general anaesthesia the
      ramus was exposed via a submandibular approach and a block of bone was removed
      from it inferior to the sigmoid notch. Temporary intermaxillary fixation was
      applied. A costochondral graft was interposed between the resected ends of bone
      and secured with mini-plates. Postoperatively intermaxillary fixation was
      maintained for 3 days after which the jaw was actively mobilized. RESULTS: The
      technique was used in the treatment of six patients with recurrent ankylosis of
      the mandible ranging in age from 9 to 38 years. Follow-up was between 1 and 4
      years. All the patients had a satisfactory interincisal opening ranging from 25
      to 35 mm. CONCLUSION: The technique does not require the exposure of the
      ankylosed joint proper but instead creates a false and functional joint at a
      lower level. It also permits lengthening and advancement of the mandible.

PMID- 16298463
TI  - A survey of the UK maxillofacial laboratory service: profiles of staff and work.
AB  - We sent questionnaires to 98 maxillofacial laboratories in the United Kingdom and
      asked about the composition of their staff, the kind of work that they do, and
      their activities in relation to the treatment of disfigured patients who require
      facial and body prostheses. We received 59 replies about 193 laboratory staff,
      most of whom had 10 or more years experience and held basic and advanced
      qualifications in dental technology. Most laboratories did all sorts of work
      including maxillofacial, orthodontic, dental prosthetic and crown and bridge
      work. Only five confined themselves to maxillofacial work. One hundred and
      eighteen staff (61%) had contact with 4,259 disfigured patients who required
      prostheses. Fifty-three laboratory managers (89%) thought that maxillofacial
      prosthetists and technologists gave psychological support to these patients, but
      only 12 laboratories (21%) had staff with formal training in counselling.

PMID- 16298464
TI  - Effect of daily physical activity on proximal femur.
AB  - BACKGROUND: The incidence of osteoporotic fractures is increasing and has become
      one of the major health problems in developed countries. Physical exercise has
      been found to be effective in the prevention of osteoporosis. However, the
      optimal amount of exercise is not known. The aim of this study was to examine the
      association between the intensity of physical activity and bone mineral density
      at the proximal femur, using long-term quantification of daily physical activity.
      METHODS: The study subjects were 64 women (age 35-40 years), who carried an
      accelerometer-based body movement recorder for 12 months for individual
      quantification of their daily physical activity. The average distribution of
      daily accelerations was defined using 33 acceleration levels. FINDINGS: A
      significant relationship between physical activity data and proximal femur bone
      mineral density was found. Physical activity that induced acceleration levels
      exceeding 3.6g correlated positively with the bone mineral density change at the
      proximal femur, the association being strongest at the femoral neck at 5.7 g (r =
      0.416, P = 0.001). INTERPRETATION: The association between physical activity and
      changes in proximal femur bone mineral density was dependent on the acceleration
      level of exercise. The quantity and quality of exercise can be monitored with the
      accelerometer-based physical activity monitor, and the method might be used for
      optimizing exercise for prevention of osteoporosis.

PMID- 16298465
TI  - Effect of sock on biomechanical responses of foot during walking.
AB  - BACKGROUND: Except the plantar pressure and gross joint motion, we know little
      about the mechanical state of a foot during walking. This study aimed at
      investigating the effect of wearing socks with different frictional properties on
      plantar shear, which is a possible mechanical risk factor of foot lesion
      development. METHOD: A 3-D finite element model for simulating the foot-sock
      insole contact was developed to investigate the biomechanical effects of wearing
      socks with different combinations of frictional properties on the plantar foot
      contact. The dynamic plantar pressure and shear stress during the stance phases
      of gait were studied through finite element computations. Three cases were
      simulated, a barefoot with a high frictional coefficient against the insole
      (0.54) and two socks, one with a high frictional coefficient against the skin
      (0.54) and a low frictional coefficient against the insole (0.04) and another
      with an opposite frictional properties assignment. FINDINGS: Wearing sock of low
      friction against the insole to allow more relative sliding between the plantar
      foot and footwear was found to reduce the shear force significantly: at the
      rearfoot from 3.1 to 0.88 N, and at the forefoot from 10.61 to 1.61 N. The shear
      force can be further reduced to 0.43 N at the rearfoot, and 1.18 N at the
      forefoot, when wearing the sock with low friction against the foot skin and high
      friction set against the insole. INTERPRETATION: Wearing sock with low friction
      against the foot skin was found to be more effective in reducing plantar shear
      force on the skin than the sock with low friction against the insole. The risk of
      barefoot walking in developing plantar shear related blisters and ulcers might be
      reduced by socks wearing especially those with low friction against the foot
      skin.

PMID- 16298466
TI  - Air-vegetation transfer of PCDD/PCDFs: an assessment of field data and
      implications for modeling.
AB  - This study was designed to evaluate soil and air (gas and particle) transfer of
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) to vegetation in
      residential and industrial areas. In a first part, soil-vegetation transfer was
      assessed. The levels of PCDD/Fs in 120 soil and 120 herbage samples collected
      from 1996 to 2002 in an industrial area of Montcada (Barcelona, Spain), near a
      municipal solid waste incinerator (MSWI), were determined. Some additional
      individual samples were also evaluated. It was concluded that high soil
      concentrations, which are not at steady state with the air layer above it, show a
      tendency for PCDD/Fs to escape via volatilization. In a second part of the study,
      air-vegetation transfer was examined. PCDD/F concentrations from 24 herbage
      samples were used, while PCDD/F concentrations were also measured in seven high
      volume air samples and seven passive air-vapor samples. Scavenging coefficients
      (m3 air "sampled"/g grass d.m.) ranged from 1.9 to 11.3 m3/g. A good trend with
      K(OA) was observed for PCDDs (R=0.82), while it was lower for PCDFs (R=0.55). The
      current results corroborate that PCDD/F concentrations in vegetation are
      associated with atmospheric deposition. For the highest substituted PCDD/F
      congeners, the air-particle uptake from plants is the principal pathway. In
      regions impacted by combustion emission sources, PCDD/F gas-particle partitioning
      is influenced by a higher concentration of particles in the air. Particles and
      associated particle-bound PCDD/Fs would sorb to leaf surfaces, and are subject to
      removal via wash off. However, in areas where emissions to air are not very
      notable, vapor absorption would be the principal source of vegetation pollution.
      The results of this investigation can have a potential interest in risk
      assessment studies and environmental fate models.

PMID- 16298467
TI  - Statistical analysis used in the nutritional assessment of novel food using the
      proof of safety.
AB  - The safety assessment of Novel Food, including GM biotechnology-derived crops,
      starts with the comparison of the Novel Food with a traditional counterpart that
      is generally accepted as safe based on a history of human food use. Substantial
      equivalence is established if no meaningful difference from the conventional
      counterpart was found, leading to the conclusion that the Novel Food is as safe
      and nutritious as its traditional counterpart. In general, the non-significance
      of p value is used for the proof of safety. From a statistical perspective, the
      problems connected with such an approach are demonstrated, namely that quite
      different component-specific false negative error rates result. As an
      alternative, the proof of safety is discussed with the inherently related
      definition of safety thresholds. Moreover, parametric and non-parametric
      confidence intervals for the difference and the ratio to control (conventional
      line) are described in detail. Finally, the treatment of multiple components for
      a global proof of safety is explained.

PMID- 16298468
TI  - Liver X receptor preferentially activates de novo lipogenesis in human
      preadipocytes.
AB  - The liver X receptor (LXR) was demonstrated to play a key role in cholesterol
      metabolism in liver, intestine and macrophage. However, its function on the
      regulation of preadipocyte differentiation remains unclear since contradictory
      results were reported. The objective of the present study was to unravel the
      functionality of LXR in human preadipocytes. We show that the LXR agonist
      T0901317 strongly stimulated the expression of SREBP-1c and the lipogenic enzymes
      ACC-1, FAS and SCD-1 in both the human preadipose cell line Chub-S7 as well as
      human primary stromal vascular fraction (SVF) cells. The effects on gene
      expression were associated with the stimulation of de novo lipogenesis in both
      cell models, resulting in the induction of lipid accumulation. In contrast with a
      PPARgamma agonist (BRL49653), T0901317 enhanced only slightly the expression of
      PPARgamma dependent genes (PPARgamma, aP2 and adiponectin) in Chub-S7 cells and
      failed to change their expression in human SVF cells. These results show that LXR
      stimulated preferentially triglyceride accumulation in human preadipocytes via
      the induction of de novo lipogenesis, rather than activating the differentiation
      process through PPARgamma activation.

PMID- 16298469
TI  - Apelin, a novel adipokine over-produced in obesity: friend or foe?

PMID- 16298470
TI  - Steroid receptor coactivator-3, a homolog of Taiman that controls cell migration
      in the Drosophila ovary, regulates migration of human ovarian cancer cells.
AB  - Border cell migration is a process that occurs during Drosophila ovarian
      development in which cells derived from a simple epithelium migrate and invade
      neighboring tissue. This process resembles the behavior of cancerous cells that
      derive from the simple epithelium of the human ovary. One important regulator of
      border cell migration is Taiman, a homolog of steroid receptor coactivator-3 (SRC
      3). Because increasing evidence indicates that similarities exist between the
      molecular control of migration of border cells and of cancer cells, we
      investigated whether SRC-3 controls ovarian cancer cell migration. Little or no
      SRC-3 expression was detected in normal ovarian surface epithelium, ovarian cysts
      and borderline ovarian tumors that lack stromal invasion. In contrast, SRC-3 was
      abundantly expressed in high-grade ovarian carcinomas. Inhibiting SRC-3
      expression in ovarian cancer cells markedly reduced cell spreading and migration,
      and altered intracellular localization of focal adhesion kinase. This inhibitory
      effect on cell migration was independent of the estrogen receptor (ER) status of
      the cells. These studies reveal a novel role for SRC-3 in ovarian cancer
      progression by promoting cell migration, independently of its role in estrogen
      receptor signaling.

PMID- 16298471
TI  - The role of cyclic AMP response element binding protein in transactivation of
      scavenger receptor class B type I promoter in transfected cells and in primary
      cultures of rat theca-interstitial cells.
AB  - In the ovary, lutropin (LH) stimulates the selective uptake and transport of
      cholesterol for steroid biosynthesis from HDL particles via the scavenger
      receptor class B type I (SR-BI). Furthermore the expression of SR-BI mRNA in the
      ovary is stimulated by LH and cyclic AMP (cAMP). Since the promoter of the rat SR
      BI gene is devoid of consensus cyclic AMP response element (CRE) sequences, this
      study examined if cAMP response element binding protein (CREB) plays a role in
      the transactivation of SR-BI promoter (SR-BIpr). The transactivation of SR-BIpr
      was examined in transfected 293T cells and human granulosa SVOG-4o cells, and in
      primary cultures of rat theca-interstitial cells infected with adenoviral
      constructs containing the SR-BIpr and a luciferase reporter gene. Dose-related
      increases in SR-BRpr activity ranging from 2- to 4-fold was induces by 293T cells
      co-transfected with the catalytic subunit of protein kinase A (cPKA). Co
      transfections with CREB and cPKA produced a concentration-dependent increase
      ranging from 6- to 32-fold. The cAMP-mediated transactivation was significantly
      attenuated by co-transfection with CREB M1, a non-phosphorylatable, dominant
      negative form of CREB. An increase in transactivation of SR-BIpr activity was
      also seen in SVOG-4o cells co-transfected with CREB. In primary cultures of rat
      theca-interstitial (T-I) cells infected with an adenoviral construct of SR-BIpr,
      forskolin produced a marked increase in promoter activity. These data indicate
      that stimulation of the cAMP-PKA-CREB pathway enhances rat SR-BIpr activity and
      substantiate the role of CREB as an intermediary in this process. The absence of
      canonical CRE sequences in the rat SR-BIpr suggests that the activation of SR-BI
      by CREB may occur either through non-canonical CRE sequences or through
      additional transcription factors that cooperate with CREB in the activation of SR
      BI promoter activity.

PMID- 16298472
TI  - Spinal cord astrocytoma presenting as "idiopathic" intracranial hypertension.
AB  - Increased intracranial pressure is rarely seen in association with spinal tumors.
      We describe a young, non-obese man who presented with increased intracranial
      pressure, papilledema and visual obscuration. Multiple cerebrospinal fluid (CSF)
      examinations with normal or minimally elevated CSF protein lead to the initial
      diagnosis of idiopathic intracranial hypertension. After a lumboperitoneal shunt
      placement a progressive thoracic myelopathy developed 7 months after onset of
      symptoms. The spinal MRI showed a low cervical-upper thoracic intramedullary
      tumor. Open biopsy confirmed a grade 3 fibrillary astrocytoma. The suspected
      mechanisms of spinal tumors causing increased intracranial pressure are reviewed
      as well as three other cases of spinal astrocytomas previously reported in the
      literature that presented with papilledema and increased intracranial pressure
      without hydrocephalus. This case illustrates that increased intracranial pressure
      may in exceptional cases of spinal tumors precede the more typical myelopathic
      presentation by months and mimic idiopathic intracranial hypertension.

PMID- 16298474
TI  - The in vitro effects of some pesticides on carbonic anhydrase activity of
      Oncorhynchus mykiss and Cyprinus carpio carpio fish.
AB  - Systemic carbonic anhydrase (CA) inhibitors are among the most powerful agents to
      lower intraocular pressure. Unfortunately, their use is frequently accompanied by
      undesired side effects. Some are due to the relatively large amounts of drug that
      have to be systematically administered to inhibit the CA in the ciliary
      processes. The aim of the present work was to study in vitro effects of some
      pesticides on CA enzyme obtained from blood of fish, which play a key role in
      salt- and osmoregulation and acid-base balance in the fish, Oncorhynchus mykiss
      and Cyprinus carpio carpio living in freshwaters, and compared with CA
      inhibitors. CA activities were significantly inhibited by pesticides and
      inhibitors. I(50) values of O. mykiss CA enzyme inhibited by lambda-cyhalothrin,
      deltametrin, diozinon, dorzolamide and brinzolamide were 6.05 x 10(-4), 1.48 x
      10(-5), 6.84 x 10(-3), 3.82 x 10(-5) and 1.80 x 10(-6) mol/l, and that for C. c.
      carpio 6.86 x 10(-4), 4.70 x 10(-4), 3.92 x 10(-3), 8.34 x 10(-6) and 1.42 x 10(
      6) mol/l, respectively. The pesticides used in this study inhibited the CA
      activity from different fish species to various degrees. It was found that the
      most effective inhibitor of CA enzyme within pesticides used was detrametrin.
      These findings observed in vitro could be useful in the understanding of the
      toxic effects that pesticides elicit on aquatic organisms in vivo.

PMID- 16298473
TI  - Xrcc2 deficiency sensitizes cells to apoptosis by MNNG and the alkylating
      anticancer drugs temozolomide, fotemustine and mafosfamide.
AB  - DNA double-strand breaks (DSBs) are potent killing lesions, and inefficient
      repair of DSBs does not only lead to cell death but also to genomic instability
      and tumorigenesis. DSBs are repaired by non-homologous end-joining and homologous
      recombination (HR). A key player in HR is Xrcc2, a Rad51-like protein. Cells
      deficient in Xrcc2 are hypersensitive to X-rays and mitomycin C and display
      increased chromosomal aberration frequencies. In order to elucidate the role of
      Xrcc2 in resistance to anticancer drugs, we compared Xrcc2 knockout (Xrcc2-/-)
      mouse embryonic fibroblasts with the corresponding isogenic wild-type and Xrcc2
      complemented knockout cells. We show that Xrcc2-/- cells are hypersensitive to
      the killing effect of the simple methylating agent N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG). They undergo apoptosis after MNNG treatment while
      necrosis is only marginally enhanced. Complementation of Xrcc2 deficient cells by
      Xrcc2 cDNA transfection conferred resistance to the cytotoxic and apoptosis
      inducing effect of MNNG. The hypersensitivity of Xrcc2-/- cells to MNNG prompted
      us to investigate their killing and apoptotic response to various methylating,
      chloroethylating and crosslinking drugs used in anticancer therapy. Xrcc2
      deficient cells were found to be hypersensitive to temozolomide, fotemustine and
      mafosfamide. They were also hypersensitive to cisplatin but not to taxol. The
      data reveal that Xrcc2 plays a role in the protection against a wide range of
      anticancer drugs and, therefore, suggest Xrcc2 to be a determinant of anticancer
      drug resistance. They also indicate that HR is involved in the processing of DNA
      damage induced by simple alkylating agents.

PMID- 16298475
TI  - Novel active heterogeneous Fenton system based on Fe3-xMxO4 (Fe, Co, Mn, Ni): the
      role of M2+ species on the reactivity towards H2O2 reactions.
AB  - In this work, the effect of incorporation of M2+ species, i.e. Co2+, Mn2+ and
      Ni2+, into the magnetite structure to increase the reactivity towards H2O2
      reactions was investigated. The following magnetites Fe3-xMnxO4, Fe3-xCoxO4 and
      Fe3-xNixO4 and the iron oxides Fe3O4, gamma-Fe2O3 and alpha-Fe2O3 were prepared
      and characterized by Mossbauer spectroscopy, XRD, BET surface area, magnetization
      and chemical analyses. The obtained results showed that the M2+ species at the
      octahedral site in the magnetite strongly affects the reactivity towards H2O2,
      i.e. (i) the peroxide decomposition to O2 and (ii) the oxidation of organic
      molecules, such as the dye methylene blue and chlorobenzene in aqueous medium.
      Experiments with maghemite, gamma-Fe2O3 and hematite, alpha-Fe2O3, showed very
      low activities compared to Fe3O4, suggesting that the presence of Fe2+ in the
      oxide plays an important role for the activation of H2O2. The presence of Co or
      Mn in the magnetite structure produced a remarkable increase in the reactivity,
      whereas Ni inhibited the H2O2 reactions. The obtained results suggest a surface
      initiated reaction involving Msurf2+ (Fe, Co or Mn), producing HO radicals, which
      can lead to two competitive reactions, i.e. the decomposition of H2O2 or the
      oxidation of organics present in the aqueous medium. The unique effect of Co and
      Mn is discussed in terms of the thermodynamically favorable Cosurf3+ and Mnsurf3+
      reduction by Femagnetite2+ regenerating the active species M2+.

PMID- 16298476
TI  - Sensor fault diagnosis for nonlinear processes with parametric uncertainties.
AB  - This paper addresses the problem of detecting, discriminating, and reconstructing
      sensor faults for nonlinear systems with known model structure but uncertainty in
      the parameters of the process. The convenience of the proposed technique lies in
      the fact that historical operational data and/or a priori fault information is
      not required to achieve accurate fault reconstruction except for fixed, short
      intervals. The overall fault diagnosis algorithm is composed of a series of
      nonlinear estimators, which estimates parameter and a fault isolation and
      identification filter. Parameter estimation and fault reconstruction cannot be
      performed accurately since faults and parametric uncertainty interact with each
      other. Therefore, these two tasks are performed at different time scales, where
      the fault diagnosis takes place at a more frequent rate than the parameter
      estimation. It is shown that the fault can be reconstructed under some realistic
      assumptions and the performance of the proposed methodology is evaluated on a
      simulated chemical process exhibiting nonlinear dynamic behavior.

PMID- 16298478
TI  - Crystal structure, thermal decomposition mechanism and explosive properties of
      [Na(H2TNPG)(H2O)2]n.
AB  - The new coordination polymer of sodium trinitrophloroglucinate,
      [Na(H2TNPG)(H2O)2]n, was synthesized by reacting trinitrophloroglucinol (H3TNPG)
      with NaHCO3 in aqueous solution and [Na(H2TNPG)(H2O)2]n was recrystallized to be
      yellow single crystal. The title compound was characterized by using elemental
      analysis and Fourier transform infrared (FT-IR) spectrum. Its crystal structure
      was determined by single crystal X-ray diffraction analysis. The crystalline
      belongs to monoclinic system and C2/c space group. Each Na+ ion is six
      coordinated to one H2TNPG- anion and four water molecules in which the oxygen
      atoms in the water molecules act as bridging atoms. Coordination bonds,
      electrostatic interaction and intermolecular hydrogen bonds assemble the ions
      into network structures. The thermal decomposition mechanism of the complex was
      studied by using differential scanning calorimetry (DSC),
      thermogravimetry/derivative thermogravimetry (TG/DTG) and FT-IR techniques. Under
      nitrogen atmosphere with a heating rate of 10 degrees C/min the thermal
      decomposition of the complex contained one endothermic and five exothermic
      processes. Two intense exothermic decomposition processes were observed in the
      range of 173-228 degrees C suggesting its energetic nature and the solid
      decomposition residue at 500 degrees C was sodium isonitrile. Explosive
      properties revealed that the compound is sensitive to mechanical stimuli. All
      properties data observed show that the title compound has explosive properties
      and can act as components of ecologically clean initiating compositions.

PMID- 16298479
TI  - Effects of tri-valent (Cr(III)) and hexa-valent (Cr(VI)) chromium on the growth
      of activated sludge.
AB  - The effects of Cr(VI) and Cr(III) species on the activated sludge growth rate
      have been assessed for a batch growth system, for a range of chromium
      concentration between 0 and 320 mg l(-1). Cr(VI) was found to stimulate microbial
      growth for concentrations up to about 25 mg l(-1), exhibiting maximum growth
      stimulation at 10 mg l(-1), whilst the lethal dose was found to be between 80 and
      160 mg l(-1). On the other hand, Cr(III) was also found to stimulate microbial
      growth for concentrations up to about 15 mg l(-1), (with a maximum stimulation
      concentration at 10 mg l(-1)), whilst the lethal dose was found to lie between
      160 and 320 mg l(-1). The results indicate that Cr(VI) is more toxic to biomass
      at relatively high concentrations (higher than 70 mg l(-1)) whilst it has a more
      pronounced growth stimulation effect at relatively smaller concentrations (less
      than 25 mg l(-1)), compared with Cr(III).

PMID- 16298477
TI  - Lead adsorption by silica-immobilized humin under flow and batch conditions:
      assessment of flow rate and calcium and magnesium interference.
AB  - Batch and column experiments were performed to determine the Pb(II) binding
      ability of silica-immobilized humin biomass under different conditions. Batch
      experiments were performed to determine the interference of Ca(II) and Mg(II) and
      column experiments were used to determine the effect of flow rate and the
      presence of Ca(II) and Mg(II) on the Pb(II) adsorption by the humin biopolymer.
      The results from the batch experiments showed that Pb binding decreased as the
      concentrations of Ca and Mg increased. At a concentration of 100 mM, the
      interference of Ca alone was 36%, while for Mg it was 26%; however, when both
      cations were present, the interference increased up to 42%. Column experiments
      were performed at flow rates of 1, 1.5, 2, and 3 mL min(-1) using a 0.1 mM Pb(II)
      solution. The results showed that the highest Pb adsorption was obtained at the
      flow rates of 1 and 1.5 mL min(-1). The average Pb binding capacity at these two
      flow rates was 182.3 +/- 0.7 microMPbg(-1). In addition, a recovery of 99.5 +/-
      0.3% was obtained. Immobilized humin exposed under flow conditions to Pb-Ca, Pb
      Mg or Pb-[Ca + Mg] solutions (Pb used at 0.1 mM and Ca and Mg at 1 mM) showed a
      Pb binding capacity of 161+/- 5, 175 +/- 5, and 171+/- 1 microM g(-1),
      respectively. In mixtures containing Pb-Ca, Pb-Mg and Pb-Ca-Mg, the Pb recovery
      was 89.8% +/- 0.35, 90.3% +/- 0.43, and 88.1% +/- 0.5, respectively. Pb recovery
      was performed using 30 bed volumes of 0.1M HCl as stripping agent. The results of
      these experiments demonstrated that silica-immobilized humin biomass has the
      potential for Pb removal from aqueous solution even in the presence of 20 mM of
      calcium and magnesium.

PMID- 16298480
TI  - Magnetic resonance imaging using hemagglutinating virus of Japan-envelope vector
      successfully detects localization of intra-cardially administered microglia in
      normal mouse brain.
AB  - Although the therapeutic use of microglia has received some attention for the
      treatment of brain diseases, few non-invasive techniques exist for monitoring the
      cells after administration. Here, we present a technique using magnetic resonance
      imaging (MRI) to track microglia injected intra-cardially. We labeled microglia
      expressing enhanced green fluorescent protein with superparamagnetic iron oxide
      (Resovist) using the hemagglutinating virus of Japan-envelope vector. We injected
      labeled microglia into the left ventricle of the heart of mice. After monitoring
      exogenously administered microglia in the mouse brain in vivo using T(2)*
      weighted MRI at a magnetic field of 7T, we compared the MR images with
      histochemical localization of exogenous microglia in vitro. MRI revealed clear
      signal changes attributable to Resovist-containing microglia in the mouse brain.
      Histochemistry demonstrated the presence of exogenous microglia in the brain at
      the same locations shown by MRI. This study demonstrates the usefulness of MRI
      for non-invasive monitoring of exogenous microglia, and suggests a promising
      future for microglia/macrophages as therapeutic tools for brain disease.

PMID- 16298482
TI  - LRRK2 G2019S is a common mutation in Spanish patients with late-onset Parkinson's
      disease.
AB  - Mutations in the leucine-rich repat kinase 2 (LRRK2) gene have been shown to
      cause both autosomal dominant and sporadic Parkinson's disease (PD). The common
      G2019S mutation shows wide geographical distribution while R1441G has been only
      reported in Northern Spain. The overall frequency of these mutations remains to
      be established. To determine the prevalence of G2019S and R1441G mutations in our
      population of Cantabria (Northern Spain), we recruited 105 consecutive PD
      patients and 310 controls and conducted genetic analysis of these mutations.
      G2019S was detected in eight late-onset patients (7.6%). Five of them had no
      relevant family history. R1441G was not detected in any of our study subjects.
      The prevalence of G2019S mutation in unselected late-onset PD patients might be
      higher than previously reported: 3/16 (18.7%) of familial PD and 5/82 (6.1%) of
      sporadic PD.

PMID- 16298481
TI  - Amantadine and memantine induce the expression of the glial cell line-derived
      neurotrophic factor in C6 glioma cells.
AB  - Aminoadamantanes are commonly used in the treatment of Parkinson's and
      Alzheimer's diseases. While these drugs are shown to antagonise ionotropic
      glutamate receptors on neuronal cells, additional mechanisms could contribute to
      their neuroprotective properties. The aim of the present study was to investigate
      the effect of aminoadamantanes on the production of the glial cell line-derived
      neurotrophic factor (GDNF) in glial cells. For this purpose, we measured the
      modulation of GDNF release in C6 glioma cell cultures treated for 24 h with
      amantadine and memantine. Both drugs dose-dependently increased GDNF level in the
      culture medium with similar potency (submicromolar range) and efficacy (three to
      four-fold induction). RT-PCR studies revealed that both compounds also increased
      GDNF mRNA levels and their influence on the GDNF gene transcription was further
      evidenced using a rat GDNF promoter luciferase reporter assay. Together, these
      results demonstrate that the neuroprotective effect of amantadine and memantine
      could involve the regulation of GDNF production by glial cells.

PMID- 16298483
TI  - The human prion gene M129V polymorphism is not associated with idiopathic
      Parkinson's disease in three distinct populations.
AB  - Coexistence of prion disease and idiopathic Parkinson's disease (IPD) has been
      previously described. It remains unclear whether this relationship may reflect
      the high incidence of IPD or whether both prion and IPD share common pathogenetic
      mechanisms. For this reason, we investigated the genotype distribution of the
      M129V polymorphism of the human prion gene for association with IPD (controls: n
      = 398, IPD cases: n = 400). No association between genotypes in codon 129 and IPD
      was detected in three distinct populations, suggesting that this PRNP
      polymorphism has no direct influence on the susceptibility to IPD.

PMID- 16298484
TI  - Type-specific evolution of amyloid plaque and angiopathy in APPsw mice.
AB  - To clarify how Abeta deposits start in the brain, we examined the early to late
      stages of senile plaques and amyloid angiopathy in APPsw mice. All types of human
      senile plaques were observed in the mouse brains. The premature forms of cored
      plaques appeared first in the cerebral cortex of mice at 7-8 months old. Then,
      amyloid angiopathy emerged, followed by diffuse plaques consisting of Abeta1-42.
      Modifications of the N-terminus of Abeta were late phase phenomena. The premature
      forms of cored plaques were composed of central Abeta1-40 amyloid cores,
      surrounding amorphous Abeta1-42 deposits, and accumulation of Abeta1-42 in some
      peripheral cells. These cells were incorporated in amyloid cores, and these
      plaques developed to large cored plaques composed of Abeta1-40 and Abeta1-42. The
      size and number of cored plaques were increased with age. These findings indicate
      different evolution paths for cored plaques and diffuse plaques, and suggest the
      presence of a pathway that initiates with the intracellular accumulation of
      Abeta1-42 and leads to the development of classic plaques in human brain tissues.

PMID- 16298485
TI  - The perception of biological motion by infants: an event-related potential study.
AB  - The current study investigates how human infants process and interpret human
      movement. Neural correlates to the perception of biological motion by 8-month-old
      infants were assessed. Analysis of event-related potentials (ERPs) resulting from
      the passive viewing of upright and inverted point-light displays (PLDs) depicting
      human movement indicated a larger positive amplitude in right parietal regions
      between 200 and 300 ms for observing upright PLDs when compared with observing
      inverted PLDs. These results show that infants at 8 months of age process upright
      and inverted PLDs differently from each other. The implications for our
      understanding of infant visual perception are discussed.

PMID- 16298486
TI  - GABA(B) receptor expression and cellular localization in gerbil hippocampus after
      transient global ischemia.
AB  - Using in situ hybridization, the expression of the GABA receptor subtype B
      subunit 1 (GABA(B) R1) and subunit 2 (GABA(B) R2) following transient global
      ischemia in the gerbil hippocampus was investigated. In sham-operated animals,
      mRNAs of both subunits were mainly detected in hippocampal pyramidal cells and
      interneurons with lower expression levels of the GABA(B) R2 in the CA1 field.
      Four days after transient cerebral ischemia, neuronal message decreased in
      conjunction with neuronal death and both receptor subunits disappeared from the
      pyramidal cell layer. However, GABA(B) R1 and GABA(B) R2 were still expressed in
      a few cells. In situ hybridization of the GABA synthesizing enzyme glutamic acid
      decarboxylase 67 (GAD67) remained unchanged after the ischemic insult. Double
      labeling experiments revealed that in the postischemic hippocampus GABA(B) R1 and
      GABA(B) R2 were not present in GFAP-reactive astrocytes, but that the surviving
      parvalbumin-containing interneurons possessed GABA(B) R1 and GABA(B) R2 mRNA.

PMID- 16298487
TI  - Mutual regulation between serine and nitric oxide metabolism in human
      glioblastoma cells.
AB  - D-Serine indirectly caused dose- and time-dependent inhibition of neuronal nitric
      oxide synthase (nNOS) without affecting endothelial nitric oxide synthase (eNOS)
      in human glioblastoma cell line U87. Activity of D-amino acid oxidase (DAAO),
      catalyzing the oxidative deamination of d-amino acid, was enhanced by NO in a
      dose-dependent manner. Recently, we have reported that serine racemase (SR) is
      inhibited by NO and activated by D-serine through nitrosylation and
      denitrosylation, respectively [K. Shoji, S. Mariotto, A.R. Ciampa, H. Suzuki,
      Regulation of serine racemase activity by D-serine and nitric oxide in human
      glioblastoma cells, Neurosci. Lett., in press]. Thus, the metabolism of both d
      serine and NO in U87 cells is functionally correlated in a complex manner.
      Suppression of NO production by d-serine in U87 cells contrasts its known action
      in enhancing nNOS in neurons.

PMID- 16298488
TI  - G-CSF protects human cerebral hybrid neurons against in vitro ischemia.
AB  - Granulocyte colony-stimulating factor (G-CSF) protects neurons against
      experimental focal cerebral ischemia. However, its neuroprotective effect on
      human brain is unknown. We sought to determine whether G-CSF can protect the
      human cerebral neurons in vitro. Human cerebral-neuroblastoma hybrid cell line
      (A1) was exposed to oxygen and glucose deprivation with or without G-CSF. G-CSF
      promoted cell survival and decreased cytotoxicity effectively at 25 ng/ml. G-CSF
      reduced early apoptotic (annexin V+/PI-), and late apoptotic or necrotic (annexin
      V+/PI+) cells, and decreased active caspase-3 immunoreactivity. G-CSF could
      protect human cerebral neurons following in vitro ischemia.

PMID- 16298490
TI  - The role of threat-expectancy in acute pain: effects on attentional bias, coping
      strategy effectiveness and response to pain.
AB  - The aims of this study were threefold. Firstly, to investigate the effect of
      increasing threat-expectancy on attentional biases towards pain-related words.
      Secondly, to determine the interaction between threat-expectancy and the
      effectiveness of two coping strategies on pain threshold and tolerance. Thirdly,
      to investigate the relationship between fear of pain and the experimental
      manipulations. One hundred undergraduate psychology students were randomly
      assigned to receive either threat-increasing or reassuring information about the
      cold pressor task. After reading the information, all participants completed the
      dot-probe task for four categories of pain-related words. Following the dot-probe
      task, participants were randomly allocated to one of two coping strategy
      conditions (focusing on affective vs sensory aspects of pain). Participants then
      completed the cold pressor task while engaging in the relevant coping strategy.
      There was a significant effect of threat on bias towards affective vs sensory
      pain words. Participants in the threat condition showed a stronger bias towards
      affective pain words. In contrast, the no-threat condition displayed a stronger
      bias towards sensory pain words. Significant interaction effects were observed
      between threat and coping strategy for threshold and tolerance. These results
      indicated that focusing on sensory pain sensations was helpful in the absence of
      threat, however, in the presence of threat was relatively unhelpful in comparison
      to focusing on the affective components of pain. The present results provide
      support for the fear-avoidance model of pain [Vlaeyen JWS, Linton SJ. Fear
      avoidance and its consequences in chronic musculoskeletal pain: a state of the
      art. Pain 2000;85:317-332] and confirm the importance of threat-expectancy in
      hypervigilance towards pain and fear avoidance.

PMID- 16298489
TI  - Sucrose-induced analgesia is related to sweet preferences in children but not
      adults.
AB  - The present study tested the hypothesis that the efficacy of sucrose in reducing
      pain during the Cold Pressor Test (CPT) was related to its hedonic value. To this
      aim, we determined the most preferred level of sucrose and the analgesic
      properties of 24% w/v sucrose during the CPT in 242, 5- to 10-year-old children
      and their mothers. Outcome measures included pain thresholds (the time at which
      discomfort was first indicated) and pain tolerance (the length of time the hand
      was kept in the cold water bath). Although children, as a group, preferred
      significantly higher sucrose concentrations than adults, there were individual
      differences that allowed us to group them on the basis of those who preferred
      sucrose concentrations below that used in the CPT (24% w/v) and those who
      preferred levels >or=24% w/v sucrose. Regardless of such groupings, sucrose was
      not an effective analgesic in adult women. Unlike adults, the more children liked
      sucrose, the better its efficacy as an analgesic. That is, children who preferred
      >or=24%w/v sucrose exhibited an increased latency to report pain and tolerated
      pain for significantly longer periods of time when sucrose was held in their
      mouths relative to water. This effect was more pronounced among normal weight
      when compared to overweight/at risk for overweight children. The role that
      dietary habits and individual differences contribute to the preferences for sweet
      taste and its physiological consequences in children is an important area for
      future research.

PMID- 16298491
TI  - Pancreatic cancer pain and its correlation with changes in tumor vasculature,
      macrophage infiltration, neuronal innervation, body weight and disease
      progression.
AB  - To begin to understand the relationship between disease progression and pain in
      pancreatic cancer, transgenic mice that develop pancreatic cancer due to the
      expression of the simian virus 40 large T antigen under control of the rat
      elastase-1 promoter were examined. In these mice precancerous cellular changes
      were evident at 6 weeks and these included an increase in: microvascular density,
      macrophages that express nerve growth factor and the density of sensory and
      sympathetic fibers that innervate the pancreas, with all of these changes
      increasing with tumor growth. In somatic tissue such as skin, the above changes
      would be accompanied by significant pain; however, in mice with pancreatic
      cancer, changes in pain-related behaviors, such as morphine-reversible severe
      hunching and vocalization only became evident at 16 weeks of age, by which time
      the pancreatic cancer was highly advanced. These data suggest that in mice as
      well as humans, there is a stereotypic set of pathological changes that occur as
      pancreatic cancer develops, and while weight loss generally tracks disease
      progression, there is a significant lag between disease progression and behaviors
      indicative of pancreatic cancer pain. Defining the mechanisms that mask this pain
      in early and mid-stage disease and drive the pain in late-stage disease may aid
      in earlier diagnosis, survival, and increased quality of life of patients with
      pancreatic cancer.

PMID- 16298492
TI  - Parent and family factors in pediatric chronic pain and disability: an
      integrative approach.

PMID- 16298493
TI  - A method for extracting muscle information from serum creatine kinase
      measurements--its potential value in the monitoring and management of
      inflammatory muscle disease.
AB  - A major problem in treating inflammatory myopathies is the very limited
      information available about the processes taking place. For instance serum
      creatine kinase levels are often dismissed as a means of gaining an understanding
      of what is happening or a means of monitoring a patient. This paper shall show
      how serum creatine kinase levels may be used to explore the processes taking
      place that create muscle inflammation. This is achieved by a detailed
      longitudinal study. Firstly, considerable laboratory data is gathered such as
      serum creatine kinase levels and blood pressure information. Secondly, the data
      is quantified using a scientific model. We shall illustrate the approach through
      an extensive nine-year study of a particular polymyositis patient. We identify
      three basic processes that may contribute to muscle inflammation and show how
      they may be interpreted from specific patient data. Furthermore, details are
      given for controlling and monitoring the disease to maximise the reduction in the
      muscle attack while reducing significantly the muscle inflammation and keeping
      the drug concentration at a minimum to ensure minimum side-effects and how to
      identify and handle drug-drug, drug-natural product and adverse drug
      interactions. Examples are given for a natural product, azathioprine and
      trandolapril.

PMID- 16298494
TI  - A chronopharmacological preventive treatment for sleep-related migraine headaches
      and chronic morning headaches: Nitric oxide supersensitivity can cause sleep
      related headaches in a subset of patients.
AB  - Frequent and recurrent migraine headaches can, over time, pose the additional
      risks of stroke, brain damage, heart failure and attention deficit. This is why
      prevention should always be a part of the treatment. Nitric oxide
      supersensitivity is the hypothesis upon which this model is based. Its role in
      causing migraine headaches and chronic morning headaches can be triggered by both
      normal and abnormal characteristics of the sleep cycle and more specifically by
      the release of nitric oxide that occurs towards the end of the sleep cycle.
      Stress and the age-related loss of sleep continuity, together with the
      corresponding increase in cortisol levels, potentiate delta rebound. Delta
      rebound results in deeper sleep intensity. It is associated with increased nitric
      oxide production. Increased delta rebound then causes an increase in the amount
      and duration of nitric oxide release at night. Migraineurs are susceptible to
      migraine headaches because they are supersensitive to nitric oxide. The diurnal
      pattern of the incidence of sleep-related headaches in a subset of the general
      population is caused by the effect of nitric oxide supersensitivity during the
      sleep cycle. The proposed treatment is for both sleep-related migraine headaches
      and chronic morning headaches. It consists of melatonin and moclobemide taken
      during the night, close the end of the sleep cycle so as to achieve the maximum
      concentrations. Both melatonin and moclobemide affect three important aspects of
      sleep-related headaches: nitric oxide supersensitivity, stress system dysfunction
      and sleep pathology. Both melatonin and moclobemide have demonstrated
      effectiveness in preventing migraine headaches. Additionally, both melatonin and
      moclobemide are compatible with most of the other therapeutic agents used to
      prevent migraine headaches and with at least 1 therapeutic agent that is used to
      treat migraine headaches.

PMID- 16298495
TI  - Homocysteine and cognition--no longer a hypothesis?

PMID- 16298496
TI  - Metabolic syndrome--neurotrophic hypothesis.
AB  - An increasing number of researchers of the metabolic syndrome assume that many
      mechanisms are involved in its complex pathophysiology such as an increased
      sympathetic activity, disorders of the hypothalamo-pituitary-adrenal axis, the
      action of chronic subclinical infections, proinflammatory cytokines, and the
      effect of adipocytokines or psychoemotional stress. An increasing body of
      scientific research in this field confirms the role of the neurotrophins and
      mastocytes in the pathogenesis of inflammatory and immune diseases. Recently it
      has been proved that neurotrophins and mastocytes have metabotrophic effects and
      take part in the carbohydrate and lipid metabolism. In the early stage of the
      metabolic syndrome we established a statistically significant increase in the
      plasma levels of the nerve growth factor. In the generalized stage the plasma
      levels of the neutrophines were statistically decreased in comparison to those in
      the healthy controls. We consider that the neurotrophin deficit is likely to play
      a significant pathogenic role in the development of the metabolic anthropometric
      and vascular manifestations of the generalized stage of MetSyn. We suggest a
      hypothesis for the etiopathogenesis of the metabolic syndrome based on the neuro
      immuno-endocrine interactions. The specific pathogenic pathways of MetSyn
      development include: (1) increased tissue and plasma levels of proinflammatory
      cytokines Interleukin-1(IL-1), Interleukin-6 (IL-6 ) and tumor necrosis factor -
      alpha (TNF-alpha) caused by inflammatory and/or emotional distress; (2) increased
      plasma levels of neurotrophin - nerve growth factor (NGF) caused by the high IL
      1, IL-6 and TNFalpha levels; (3) high plasma levels of NGF which enhance
      activation of: the autonomous nerve system--vegetodystonia (disbalance of
      neurotransmitters); Neuropeptide Y (NPY)--enhanced feeding, obesity and increased
      leptin plasma levels; hypothalamo-pituitary-adrenal axis--increased corticotropin
      releasing hormone (CRH) and cortisol (hormonal disbalance); immune cells-
      increased number and degranulation of mastocytes (MC)--immunological disbalance;
      (4) as a result of 1-3 insulin resistance is exhibited leading to diabetes
      mellitus. The hypothesis is confirmed by results obtained after 6-month
      nonsteroid anti-inflammatory treatment of patients with MetSyn. These results are
      reported in a separate publication.

PMID- 16298497
TI  - Epilepsy and migraine: The dopamine hypotheses.
AB  - Migraine and epilepsy are both chronic recurrent disorders with paroxysmal
      attacks. They also share some similar risk factors, symptoms, and preventive
      medications. Dopamine has long been postulated to be involved in the
      pathophysiology of migraine and epileptogenesis, by many supporting evidences.
      However, the role of dopamine is still controversial till now. A lack of a
      comprehensive hypothetical model may be one of the reasons. "Dopamine hypothesis"
      is not a new term, but it is proposed to explain the pathophysiology and the
      associated phenomena of these disorders. The hypotheses suggest that, in
      migraine, there is a low dopamine tone, while there is a high state of dopamine
      in generalized epilepsy. But the periodic attacks of headaches and seizures maybe
      both due to a fall in dopamine activity. Dopamine therefore plays a key role in
      the linkage of neuroendocrine, autonomic system and neuronal activity. Dopamine
      agonist is also implied in prophylaxis and neuroprotection in both disorders.

PMID- 16298498
TI  - Renal mobility during uncoached quiet respiration: an analysis of 4DCT scans.
AB  - PURPOSE: Data on organ mobility is required for optimizing radiotherapy. Renal
      mobility was studied in four-dimensional computed tomography (4DCT) scans
      acquired during uncoached respiration. METHODS AND MATERIALS: The 4DCT scans of
      54 patients, in whom at least the upper pole of both kidneys were visualized in
      all 10 respiratory phases, were analyzed. Scans were performed on a 16-slice CT
      scanner (slice index and reconstruction, 2.5 mm) during quiet, uncoached
      respiration. Mobility of the renal apex was evaluated in all patients by use of
      the z-position on CT slices. Reproducibility of mobility was studied in 8
      patients who underwent 1 or 2 repeat 4DCT scans. RESULTS: Mobility was
      predominantly craniocaudal, with a mean of 9.8 mm for the left kidney and 9.0 mm
      for the right kidney. Large interpatient variations were observed that ranged
      from 2.5 to 30 mm (left) and 2.5 to 20 mm (right), and mobility of 1 kidney did
      not predict for mobility of the contralateral organ. Reproducibility of renal
      mobility and position at end-expiration was poor, with positional variations in
      repeat scans appearing to correlate with changes in the amplitude of respiratory
      waveform and total lung volume. CONCLUSIONS: Large interpatient variations in
      renal movement occur during uncoached respiration, which indicates that
      respiratory coaching is useful for 4DCT imaging and treatment delivery.

PMID- 16298499
TI  - Survival prediction in high-grade gliomas by MRI perfusion before and during
      early stage of RT [corrected].
AB  - PURPOSE: To determine whether cerebral blood volume (CBV) and cerebral blood flow
      can predict the response of high-grade gliomas to radiotherapy (RT) by taking
      into account spatial heterogeneity and temporal changes in perfusion. METHODS AND
      MATERIALS: Twenty-three patients with high-grade gliomas underwent conformal RT,
      with magnetic resonance imaging perfusion before and at Weeks 1-2 and 3-4 during
      RT. Tumor perfusion was classified as high, medium, or low. The prognostic values
      of pre-RT perfusion and the changes during RT for early prediction of tumor
      response to RT were evaluated. RESULTS: The fractional high-CBV tumor volume
      before RT and the fluid-attenuated inversion recovery imaging tumor volume were
      identified as predictors for survival (p = 0.01). Changes in tumor CBV during the
      early treatment course also predicted for survival. Better survival was predicted
      by a decrease in the fractional low-CBV tumor volume at Week 1 of RT vs. before
      RT, a decrease in the fractional high-CBV tumor volume at Week 3 vs. Week 1 of
      RT, and a smaller pre-RT fluid-attenuated inversion recovery imaging tumor volume
      (p = 0.01). CONCLUSION: Early temporal changes during RT in heterogeneous regions
      of high and low perfusion in gliomas might predict for different physiologic
      responses to RT. This might also open the opportunity to identify tumor
      subvolumes that are radioresistant and might benefit from intensified RT.

PMID- 16298500
TI  - Detection of lymphocystis disease virus (LCDV) in asymptomatic cultured gilt-head
      seabream (Sparus aurata, L.) using an immunoblot technique.
AB  - An immunoblot technique for the detection of lymphocystis disease virus (LCDV) in
      naturally infected gilt-head seabream (Sparus aurata, L.) has been developed. A
      specific antiserum against a 60 kDa viral protein has been proven to be an
      appropriate tool for LCDV diagnosis either from inoculated cell cultures or from
      fish tissues using the immunoblot assay. The sensitivity of this technique varied
      between 10(-1) and 10(2) TCID50. LCDV has also been detected in fish tissues from
      both, diseased and asymptomatic gilt-head seabream. For the asymptomatic fish
      detection, a viral amplification step in cell culture and a subsequent viral
      concentration using polyethylene glycol (PEG) (600 wt) are required. On the
      contrary, immunoblot allowed the detection of LCDV antigens directly from tissue
      homogenates of diseased fish. The method described in this study shows higher
      sensitivity than classical detection techniques based on cell culture
      inoculation.

PMID- 16298502
TI  - Use patterns and knowledge of medicinal species among two rural communities in
      Brazil's semi-arid northeastern region.
AB  - The present work seeks to quantify the knowledge of two rural communities in the
      semi-arid region of the state of Pernambuco (northeastern Brazil) concerning two
      species of native medicinal plants: "aroeira do sertao", Myracrodruon urundeuva
      (Engl.) Fr. All. (Anacardiaceae) and "angico", Anadenanthera colubrina (Vell.)
      Brenan (Mimosaceae). Semi-structured interviews were carried out, combined with a
      checklist/inventory method, which yielded different indexes for quantifying
      knowledge and use of these species. In addition, the reliability of local
      knowledge was tested using analytical techniques to determine actual tannin
      concentrations. Although both communities possess knowledge concerning these two
      species, one of them stood out in terms of the diversity of information presented
      (P < 0.05), a difference that may be related to its lower degree of
      modernization. In general, older people had a greater variety of information
      about these plants, although both men and women demonstrated similar knowledge.
      Of the 101 people interviewed in Riachao, 85% stated that they knew of uses for
      both species studied; in Ameixas, of the 55 interviewees, 63% responded that they
      knew of uses for Myracrodruon urundeuva, and 45% knew of uses for Anadenanthera
      colubrina. A total of 97 different uses were reported by all informants for the
      two species studied. Of these, 62 were mentioned in only a single community,
      confirming our hypothesis of differences in knowledge between them. Informants
      from both communities knew of a great variety of uses for these plants as well as
      a number of different collection techniques. We expected that knowledge about the
      two species would differ in relation to both gender and age, but this was only
      true for one of the communities. Greater concentrations of tannins were expected
      to be found consistently in the tree bark, but experimental data demonstrated
      that tannin concentrations can vary among plant parts during the year.

PMID- 16298501
TI  - Interactions of water with the surfaces of crystal polymorphs.
AB  - The purpose of this study is to investigate the interactions of water adsorption
      on the surfaces of different crystal forms of the same drug. The energy of
      interaction between water vapor and the surfaces of the two crystal polymorphs
      has been investigated as a function of temperature and water activity. One of the
      adsorbents, the metastable form of the monotropically related pair used here,
      showed greater adsorptive capacity in terms of both the amount of water uptake as
      well the integral heat of adsorption. However, the specific heat of adsorption
      values revealed that even though the surface of the thermodynamically stable
      crystal adsorbs less water, water molecules are actually more strongly bound when
      adsorbed on the surface of the stable crystal form. This means that the
      metastable crystal form adsorbs a greater amount of more weakly bound water.
      Conversely, the thermodynamically stable form, presents on its surface a smaller
      number of stronger adsorption sites for water. This study also shows that the
      crystalline character of the surfaces of the two polymorphs, shown as
      quantifiable differences in their surface interactions, is maintained despite the
      presence of any crystal defects incorporated upon milling.

PMID- 16298503
TI  - Anti-diabetic potentials of Momordica charantia and Andrographis paniculata and
      their effects on estrous cyclicity of alloxan-induced diabetic rats.
AB  - Momordica charantia and Andrographis paniculata are the commonly used herbs by
      the diabetic patients in Pampanga, Philippines. While the anti-diabetic potential
      of Momordica charantia is well established in streptozocin- or alloxan-induced
      diabetic animals, the anti-diabetic potential of Andrographis paniculata in
      alloxan-induced diabetic rat is not known. Neither the effects of these herbs on
      estrous cyclicity of alloxan-induced diabetic rats are elucidated. Thus, in these
      experiments, Momordica charantia fruit juice or Andrographis paniculata decoction
      was orally administered to alloxan-induced diabetic rats. Rats that were treated
      with Momordica charantia and Andrographis paniculata had higher body weight (BW)
      compared with diabetic positive control (P < 0.01) from day 22 to day 27 (D27)
      but exhibited lower BW than the non-diabetic control (P < 0.05). These rats had
      lower feed (P < 0.05) and liquid intakes (P < 0.01) compared with diabetic
      positive control from day 17 to D27, but similar with the non-diabetic control.
      The blood glucose levels in these groups were significantly reduced from day 12
      to D27 compared with diabetic positive control (P < 0.01), however, comparable
      with non-diabetic control. The diabetic positive control had extended mean
      estrous cycles (8 days) compared to Momordica charantia and Andrographis
      paniculata-treated diabetic rats (5 days; P < 0.05). Our results suggest that the
      anti-diabetic potentials of Momordica charantia and Andrographis paniculata could
      restore impaired estrous cycle in alloxan-induced diabetic rats.

PMID- 16298504
TI  - Population genetics for Y-chromosomal STRs haplotypes of Chinese Tibetan ethnic
      minority group in Tibet.
AB  - Y-chromosomal STRs loci were analyzed from a sample of 119 healthy unrelated
      autochthonous male individuals of Chinese Tibetan ethnic minority group using a
      multiplex PCR system. Allele and haplotype frequencies for DYS19, DYS389 I,
      DYS389 II, DYS390, DYS391, DYS392, DYS393, DYS385a,b, DYS438, and DYS439 were
      determined by the Y-PLEXtrade mark 12 kit. The gene diversity values for the Y
      STRs loci ranged from 0.3347 (DYS438) to 0.9547 (DYS385a,b). A total of 110
      haplotypes were identified in the Y-STR loci, among which 104 were unique, while
      six occurred more than once. The overall haplotype diversity for the Y-STRs loci
      was 0.9981, and the discrimination capacity was 0.9897. The results in the
      present study can be used for routine forensic application in the region, and
      enrich Chinese ethnical genetic informational resources.

PMID- 16298505
TI  - Referral guidelines for suspected cancer of the head and neck.
AB  - OBJECTIVE: To identify the impact of referral guidelines for head and neck cancer
      on the economics and effectiveness of the delivery of care. METHODS: A
      retrospective review of the literature was performed to examine the current
      referral guidelines and referral models that have impacted the delivery of care.
      RESULTS: Advances in technology and changes in the diagnostic work up of head and
      neck cancer require that common symptoms and presentations of head and neck
      cancer are made available to primary care physicians to improve the expeditious
      referral of head and neck cancer patients. CONCLUSION: Physician awareness and
      symptom guidelines may prove effective in expediting the care of patients with
      head and neck cancer.

PMID- 16298506
TI  - Development and validation of a gradient HPLC method for the determination of
      clindamycin and related compounds in a novel tablet formulation.
AB  - A gradient reversed-phase HPLC method was developed and validated for potency,
      content uniformity, and impurity determinations for a novel tablet formulation
      containing clindamycin. The assay utilized UV detection at 214 nm and a Waters
      Xterra RP18 column (4.6 mm x 100 mm, 3.5 microm). The mobile phases were
      comprised of pH 10.5, 10 mM carbonate buffer and acetonitrile. Validation
      experiments were performed to demonstrate specificity, linearity, accuracy (i.e.,
      average recovery from the formulation), precision (i.e., repeatability), limit of
      quantitation (LOQ), and robustness (i.e., sample solution stability and buffer pH
      effects on specificity). The assay was shown to be specific for clindamycin,
      several impurities, and triethyl citrate, a retained excipient that was present
      in the dosage form. The assay was proved linear (concentration versus peak area)
      for clindamycin and several select impurities over the ranges of 70-130% and 0.1
      5%, respectively. UV relative response factors were determined for the impurities
      from the linearity data. The accuracy of clindamycin at the targeted assay
      concentration was 99.2% (n = 3; precision = 0.12%, R.S.D.); accuracy for
      lincomycin, a structurally related impurity, was 97.4% (n = 3; precision = 3.5%,
      R.S.D.) at 0.1% of the targeted assay concentration. By demonstrating an
      acceptable degree of precision for lincomycin at this level, the LOQ was shown to
      be no higher than 0.1%. The chromatography was virtually unaffected over a mobile
      phase buffer pH range spanning 0.4 pH units. Sample solutions were stable for 72
      h under ambient conditions.

PMID- 16298507
TI  - Simple, sensitive and rapid LC-ESI-MS method for the quantitation of lafutidine
      in human plasma--application to pharmacokinetic studies.
AB  - A sensitive and specific liquid chromatography electrospray ionization mass
      spectrometry (LC-ESI-MS) method has been developed and validated for the
      identification and quantification of lafutidine in human plasma. Lafutidine and
      internal standard were isolated from plasma samples by liquid-liquid extraction
      with diethyl ether. The chromatographic separation was accomplished on a
      stainless-steel column (C18 Shim-pack 5 microm 150 mm x 2.0 mm i.d. Shimadzu) at
      a flow rate of 0.2 ml/min by a gradient elution. Detection was performed on a
      single quadrupole mass spectrometer by selected ion monitoring (SIM) mode via
      electrospray ionization (ESI) source. The method was proved to be sensitive and
      specific by testing six different plasma batches. Linearity was established for
      the range of concentrations 1.0-400.0 ng/ml with a coefficient of determination
      (r) of 0.9998 and good back-calculated accuracy and precision. The intra- and
      inter-day precision (R.S.D.%) was lower than 10% and accuracy ranged from 85 to
      115%. The lower limit of quantification was identifiable and reproducible at 0.5
      ng/ml with 0.2 ml plasma. The proposed method enables the unambiguous
      identification and quantification of lafutidine for pharmacokinetic,
      bioavailability or bioequivalence studies.

PMID- 16298508
TI  - Biological and biomedical aspects of genetically modified food.
AB  - Genetically modified (GM) foods are the product of one of the most progressive
      fields of science-biotechnology. There are major concerns about GM foods in the
      public; some of them are reasonable, some of them are not. Biomedical risks of GM
      foods include problems regarding the potential allergenicity, horizontal gene
      transfer, but environmental side effects on biodiversity must also be recognized.
      Numerous methods have been developed to assess the potential risk of every GM
      food type. Benefits of the first generation of GM foods were oriented towards the
      production process and companies, the second generation of GM foods offers, on
      contrary, various advantages and added value for the consumer. This includes
      improved nutritional composition or even therapeutic effects. Recombinant
      probiotics and the principle of alternative gene therapy represent the latest
      approach of using GM organisms for biomedical applications. This article tries to
      summarize and to explain the problematic topic of GM food.

PMID- 16298509
TI  - Autoradiographic localization and binding study of benzodiazepines receptor sites
      in carp brain (Cyprinus carpio L.).
AB  - This study demonstrates, for the first time, by both autoradiography and binding
      assay that [3H]Ro 15-1788 binds to carp brain with a high degree of anatomical
      selectivity. Saturation binding of the radioligand was determined in seven
      anatomically defined regions and suggested the presence of one class of binding
      sites (Type I-lke). In general, there was a good correlation between the
      autoradiographic and the binding data. By far, the optic tectum and the vagal,
      facial, and glossopharyngeal lobes showed the majority of [3H]Ro 15-1788 binding
      sites. Low to negative concentration of binding sites was detected in the
      cerebellum. The location of [3H]Ro 15-1788 binding sites in particular brain
      regions, indicates that benzodiazepine receptors could be associated with
      pathways involved in the control of basic central functions as spatial learning
      acquisition and retention, and feeding behaviour.

PMID- 16298511
TI  - Physiopathology and genetics of vitiligo.
AB  - Generalized vitiligo is an acquired disorder in which white patches of skin and
      overlying hair result from autoimmune loss of melanocytes from involved areas.
      The autoimmune pathogenesis of vitiligo has become a rapidly evolving field of
      research. A humoral immune reaction has been implicated through the detection of
      circulating antibodies. However, recent research focuses on a melanocyte-specific
      cytotoxic-T-cell immune reaction in the melanocyte destruction. Several candidate
      genes have been proposed for vitiligo susceptibility. They include genes
      important for melanin biosynthesis, response to oxidative stress and/or
      regulation of autoimmunity. A recent genome-wide scan performed on families with
      numerous members presenting vitiligo has clearly revealed linkage of
      susceptibility loci.

PMID- 16298512
TI  - Regulation of Stat3 nuclear import by importin alpha5 and importin alpha7 via two
      different functional sequence elements.
AB  - Regulated import of STAT proteins into the nucleus through the nuclear pores is a
      vital event. We previously identified Arg214/215 in the coiled-coil domain and
      Arg414/417 in the DNA binding domain involved in the ligand-induced nuclear
      translocation of Stat3. In this study, we investigated the mechanism for Stat3
      nuclear transport. We report here that among five ubiquitously expressed human
      importin alphas, importin alpha5 and alpha7, but not importin alpha1, alpha3, and
      alpha4, bind to Stat3 upon cytokine stimulation. Similar results were observed
      for Stat1, but not for Stat5a and 5b, which were unable to interact with any of
      the importin alphas. The C-terminus of importin alpha5 is necessary but not
      sufficient for Stat3 binding. Truncation mutant of Stat3 (aa1-320) that contains
      Arg214/215 exhibits specific binding to importin alpha5, and an exclusive nuclear
      localization. Point mutations of Arg214/215 in this mutant destroy importin
      alpha5 binding and its nuclear localization. In contrast, the truncation mutant
      (aa320-770) including Arg414/417 fails to interact with importin alpha5 and is
      localized in the cytoplasm. However, both sequence elements are necessary for the
      full-length Stat3's interaction with importin alpha5. These results suggest that
      Arg214/215 is likely the binding site for importin alpha5, whereas Arg414/417 may
      not be involved in the direct binding, but necessary for maintaining the proper
      conformation of Stat3 dimer for importin binding. A model for Stat3 nuclear
      translocation is proposed based on these data.

PMID- 16298513
TI  - Detection of p16 promoter methylation in the serum of oral cancer patients.
AB  - P16 promoter methylation occurs frequently in oral squamous cell carcinoma
      (OSCC). For the early detection of tumour-related aberrant DNA, we examined p16
      methylation using the methylation-specific polymerase chain reaction (MSP) in
      tumour and serum samples of 17 OSCC patients. Aberrant p16 methylation was
      detected in 11 (64.7%) cases of primary OSCC. Of these 11 patients, 6 (54.5%)
      showed the same alteration in their serum. No methylation was found in control
      groups. Interestingly, DNA was detected in the serum of 3 out of 4 patients with
      recurrence. These results suggest that the MSP may be a sensitive and useful
      method for detecting recurrent OSCC.

PMID- 16298510
TI  - Dysmorphic and anthropometric outcomes in 6-year-old prenatally cocaine-exposed
      children.
AB  - Dysmorphologic and anthropometric assessments were performed on 154 6-year-old
      children prenatally exposed to cocaine (PCE) and 131 high-risk controls (NCE) of
      similar race and social class. Adjusted mean height z scores demonstrated a dose
      response with metahydroxybenzoylecgonine above a threshold of 100 ng/g of
      meconium and greater cocaine exposure predicted lower weight for height z score.
      Higher average alcohol exposure throughout pregnancy and 3rd trimester predicted
      lower head circumference and weight z scores, respectively. Severity of marijuana
      use also predicted lower height for age but greater weight for height. There was
      not an increased rate of minor anomalies among the PCE cohort, nor was a
      consistent phenotype identified. After controlling for covariates, higher average
      prenatal cigarette exposure predicted higher incidence of cranial facial
      abnormalities. First trimester alcohol exposure predicted greater rates of ear
      abnormalities and third trimester marijuana exposure predicted greater rates of
      chest and head shape abnormalities. These finding indicate that prenatal cocaine
      exposure has a negative effect on specific growth outcomes including standardized
      height and weight for height, but not a systematic pattern of structural
      abnormalities.

PMID- 16298514
TI  - Antidepressants use in children and adolescents and the risk of suicide.
AB  - OBJECTIVE: Antidepressants use in paediatric patients has been linked with risk
      of suicidal behaviours. The aim of this paper, therefore, is to examine whether
      all antidepressants are associated with such risk. METHOD: All 22 paediatric
      short-term placebo-controlled trials of SSRIs and NSRIs that were submitted to
      European registration authorities by pharmaceutical companies were identified and
      examined for events related to suicidality, which were defined as suicide,
      suicide attempts or suicidal thoughts. Random effect meta-analysis was used to
      combine the information from all trials. RESULTS: No completed suicides were
      reported. However, for each compound there was at least one study with an
      increased risk for events related to suicidality in the active compound group.
      The overall OR for these events in the depression studies was 1.67 (95% CI: 1.05
      2.65) and for anxiety 1.33 (95% CI: 0.33-5.35). CONCLUSIONS: Caution is called
      for in the use of all SSRIs and NSRIs in the paediatric population. Furthermore,
      in the absence of contradictory information, caution in the use of other
      antidepressants in this population should be exercised as well (e.g. tricyclic
      antidepressants).

PMID- 16298515
TI  - Electron-nuclear cross polarization.
AB  - We describe the coherent polarization transfer from an unpaired electron to
      neighboring nuclei via electron-nuclear cross polarization (eNCP) in a doubly,
      tilted rotating frame. Although the experiment superficially resembles the well
      known Hartmann-Hahn cross polarization (CP) process introduced by Pines et al.,
      that is widely used in solid-state nuclear magnetic resonance (SSNMR), it differs
      in significant respects. In particular, eNCP requires an alternative treatment
      due to the very different sizes of the specific terms in the spin Hamiltonian. We
      derive analytical expressions for the matching condition for optimal polarization
      transfer and verify their correctness with experimental results obtained with
      electron detected CP experiments performed on powder samples of BDPA radical
      dispersed in a protonated polystyrene matrix and with numerical simulations. We
      use fully protonated BDPA as an example of polarization transfer to strongly
      coupled nuclei. In contrast, perdeuterated BDPA serves as an example of the
      transfer of polarization from electrons to weakly coupled nuclei. In addition, we
      performed CP on a paramagnetic crystal to determine the influence of resolved
      hyperfine structure on the CP process. It is shown that almost no structure is
      observed in the corresponding electron-(1)H CP matching curve. It appears that
      only a restricted number of hyperfine coupled (1)H's contribute to the observed
      signal intensities in the CP experiment.

PMID- 16298516
TI  - Characterization of latex particles for aqueous polymeric coating by
      electroacoustic method.
AB  - Concentrated dispersions are used as coating dispersions for aqueous polymeric
      coatings, and characterization of the actual concentrated dispersions is an
      important in the pharmaceutical industry. The commonly used aqueous coating
      polymers are acrylic polymers and cellulose derivatives. We conducted a
      characterization study of polymethacrylate-based aqueous polymeric latex for
      aqueous coating, Eudragit L30D-55 (A-latex) and Eudragit RL30D (C-latex), by
      electroacoustic method. Colloidal Vibration Current (CVI) is one of the most
      important parameters relating to dynamic electrophoretic mobility and zeta
      potential, so we evaluated this parameter first. Volume fractions var of the
      latex in concentrated dispersions affect the CVIs according to the theory of
      Dukhin et al. The A-latex and C-latex CVI(*)s which were corrected with regard to
      the effect of volume fraction by the theoretical equation were nearly constant
      independent of phi in the ranges >0.04 and >0.03, respectively. The zeta
      potentials and colloidal stabilities of the concentrated dispersions were
      evaluated using an electroacoustic method by altering the pH and salt
      concentration. A-latex strongly aggregated at and below pH 2.5 and at and beyond
      0.06 mol/L of electrolyte concentration. Regarding C-latex, instable dispersion
      was observed at 0.3 and 1 mol/L of NaCl concentration. The total potential energy
      of interaction between pairs of latex particles was changed by altering the salt
      concentration in this dispersion based on DLVO theory. The experimental results
      of stability in the concentrated latex dispersions can be explained by the total
      interaction energies.

PMID- 16298517
TI  - Specificity of sensorimotor learning and the neural code: neuronal
      representations in the primary motor cortex.
AB  - Human studies show that the learning of a new sensorimotor mapping that requires
      adaptation to directional errors is local and generalizes poorly to untrained
      directions. We trained monkeys to learn new visuomotor rotations for only one
      target in space and recorded neuronal activity in the primary motor cortex
      before, during and after learning. Similar to humans, the monkeys showed poor
      transfer of learning to other directions, as observed by behavioral aftereffects
      for untrained directions. To test for internal representations underlying these
      changes, we compared two features of neuronal activity before and after learning:
      changes in firing rates and changes in information content. Specific elevations
      of firing rate were only observed in a subpopulation of cells in the motor cortex
      with directional properties corresponding to the locally learned rotation; namely
      cells only showed plasticity if their preferred direction was near the training
      one. We applied measures from information theory to probe for learning-related
      changes in the neuronal code. Single cells conveyed more information about the
      direction of movement and this specific improvement in encoding was correlated
      with an increase in the slope of the neurons' tuning curve. Further, the improved
      information after learning enabled a more accurate reconstruction of movement
      direction from neuronal populations. Our findings suggest a neural mechanism for
      the confined generalization of a newly acquired internal model by showing a tight
      relationship between the locality of learning and the properties of neurons. They
      also provide direct evidence for improvement in the neural code as a result of
      learning.

PMID- 16298518
TI  - [Targeted therapies in pediatric oncology: a new therapeutic approach?].
AB  - A multidisciplinary therapeutic approach has led to significant increase in
      survival of children with cancer, however often with a high rate of severe
      sequela. Better understanding in tumor cell biology and transformation process
      allowed to describe active tyrosine kinases (mainly growth factor receptors) as a
      new target for cancer treatment. This review presents 2 approaches to target
      receptor tyrosine kinase activity: on one hand, antibodies that target the
      extracellular domain, the natural ligand binding site, and on the other hand,
      small inhibiting molecules, such as imatinib, targeted against the activated
      intracellular receptor tyrosine kinase. We focus on their clinical development
      and current application in the treatment of childhood cancer. Targeted therapies
      are in full rise and new perspectives are explored, such as their association to
      other treatment modalities and the targeting of microenvironment. This new
      therapeutic approach necessitates well designed clinical trials that include
      relevant biomarkers to evaluate its real therapeutic potential.

PMID- 16298519
TI  - Dyspnoea with activities of daily living versus peak dyspnoea during exercise in
      male patients with COPD.
AB  - Dyspnoea measurements in chronic obstructive pulmonary disease (COPD) can be
      broadly divided into two categories: those that assess breathlessness during
      exercise, and those that assess breathlessness during daily activities. We
      investigated the relationships between dyspnoea at the end of exercise and during
      daily activities with clinical measurements and mortality in COPD patients. We
      examined 143 male outpatients with moderate to very severe COPD. The peak Borg
      score at the end of progressive cycle ergometry was used for the assessment of
      peak dyspnoea rating during exercise, and the Baseline Dyspnea Index (BDI) score
      was used for dyspnoea with activities of daily living. Relationships between
      these dyspnoea ratings with other clinical measurements of pulmonary function,
      exercise indices, health status and psychological status were then investigated.
      In addition, their relationship with the 5-year mortality of COPD patients was
      also analyzed to examine their predictive ability. Although the BDI score was
      significantly correlated with airflow limitation, diffusing capacity, exercise
      indices, health status and psychological status, the Borg score at the end of
      exercise had non-existent or only weak correlations with them. The BDI score was
      strongly significantly correlated with mortality, whereas the Borg score was not.
      Dyspnoea during daily activities was more significantly correlated with objective
      and subjective measurements of COPD than dyspnoea at the end of exercise. In
      addition, the former was more predictive of mortality. Dyspnoea with activities
      of daily living is considered to be a better measurement for evaluating the
      disease severity of COPD than peak dyspnoea during exercise.

PMID- 16298520
TI  - Effect of temperature and organic nutrients on the biodegradation of linear
      alkylbenzene sulfonate (LAS) during the composting of anaerobically digested
      sludge from a wastewater treatment plant.
AB  - Limits on the application of biosolids (anaerobically processed sludges from
      wastewater treatment plants) as fertilizers for the amendment of soil are
      becoming greater because of the accumulation of recalcitrant substances, making
      necessary the use of techniques that bring the concentration of xenobiotics to
      lower concentrations than those permitted. In general, the biosolids composting
      process is sufficient to reduce the usual concentration of linear alkylbenzene
      sulfonates (LAS) to low levels. In this work, an assessment is made on the effect
      of temperature in the capacity of enriched bacterial populations to biodegrade
      LAS, together with the influence that the available nutrients may have in the
      biodegradation of these compounds. The results show that the microbial metabolism
      of LAS was not observed in the thermophilic range. The optimum temperature for
      the biodegradation of LAS appears to be around 40 degrees C, this is, the lowest
      assayed here, and at this temperature the differences in the biodegradation of
      LAS among the nutritionally supplemented cultures are small.

PMID- 16298521
TI  - Optical microbial biosensor for detection of methyl parathion pesticide using
      Flavobacterium sp. whole cells adsorbed on glass fiber filters as disposable
      biocomponent.
AB  - An optical microbial biosensor was described for the detection of methyl
      parathion pesticide. Whole cells of Flavobacterium sp. were immobilized by
      trapping in glass fiber filter and were used as biocomponent along with optic
      fiber system. Flavobacterium sp. has the organophosphorus hydrolase enzyme, which
      hydrolyzes the methyl parathion into detectable product p-nitrophenol. The
      immobilized microbial biocomponent was disposable, cost-effective and showed high
      reproducibility and uniformity. The detection of methyl parathion by the use of
      disposable microbial biocomponent with optical biosensor was simple, single step
      and direct measurement of very low quantity of the sample. The home made reaction
      vessel was small and needed only 75 microl of sample. A lower detection limit 0.3
      microM methyl parathion was estimated from the linear range (4-80 microM) of
      calibration plot of organophosphorus hydrolase enzymatic assay. The applicability
      to synthetic methyl parathion spiked samples was demonstrated.

PMID- 16298522
TI  - Does a patient's self-reported health-related quality of life predict survival
      beyond key biomedical data in advanced colorectal cancer?
AB  - The purpose of this study was to determine whether baseline patients' self
      reported health-related quality of life (HRQOL) parameters could predict survival
      beyond key biomedical prognostic factors in patients with metastatic colorectal
      cancer. The analysis was conducted on 299 patients. HRQOL baseline scores were
      assessed using the European Organisation for Research and Treatment of Cancer,
      Quality of Life Questionnaire-Core30 (EORTC QLQ-C30). The Cox proportional
      hazards regression model was used for both univariate and multivariate analyses
      of survival. In addition, a bootstrap resampling technique was used to assess the
      stability of the outcomes. The final multivariate Cox regression model retained
      four variables as independent prognostic factors for survival: white blood cell
      (WBC) count with a hazard ratio (HR) of 1.961 (95% CI, 1.439-2.672; P<0.001),
      alkaline phosphatase with HR=1.509 (95% CI, 1.126-2.022; P=0.005), number of
      sites involved with HR=1.108 (95% CI, 1.024-1.198; P=0.01) and the patient's
      score on the social functioning scale with HR=0.991 (95% CI, 0.987-0.996;
      P<0.001) which translates into a 9% decrease in the patient's hazard of death for
      any 10 point increase. The independent prognostic importance of social
      functioning and the stability of the final Cox regression model were also
      confirmed by the additional bootstrap model averaging analysis, based on 1000
      bootstrap-generated samples. The results suggest that social functioning, acts as
      a prognostic measure of survival beyond a number of previously known biomedical
      parameters.

PMID- 16298523
TI  - The influence of storage conditions of tuna viscera before fermentation on the
      chemical, physical and microbiological changes in fish sauce during fermentation.
AB  - Effect of storage condition of tuna viscera on chemical, physical and
      microbiological changes of its sauce were monitored. Results based on microbial
      counts, protein degradation products, total volatile base (TVB), and
      trimethylamine (TMA) contents, showed that tuna viscera stored at room
      temperature underwent more deterioration than that kept in ice, especially with
      increasing storage time. As a result, fish sauce obtained from tuna viscera
      stored at room temperature for a longer time rendered the greater amino nitrogen,
      TVB, TMA contents as well as browning intensity. However, storage conditions had
      no marked effect on overall changes in chemical, physical and microbiological
      characteristics of sauce generated during fermentation. Additionally, fish sauce
      produced from tuna viscera kept at room temperature comprised lower histamine
      content than that prepared from fresh or ice-stored viscera. Therefore, tuna
      viscera stored at room temperature for up to 8h could be used for the production
      of fish sauce with no detrimental effect on the quality.

PMID- 16298524
TI  - Role of various parameters in synthesis of insoluble agrobased xanthates for
      removal of copper from wastewater.
AB  - The research identifies and studies the parameters involved in the synthesis of
      two types of insoluble agrobased xanthates, named insoluble baggase xanthate
      (IBX) and insoluble wood xanthate (IWX) and their ability to remove heavy metals
      from wastewater. Copper was selected as the model metal and the metal removal
      capacity of IBX and IWX were expressed by copper loading (mg of copper removed/g
      of IBX or IWX). It was observed that contact times of 3 h and alkali strengths of
      4 mol/L were necessary during alkalization. The maximum base material to alkali
      ratio (w/w) was 1.125 without sacrificing proper mixing of the base material
      alkali mixture. Optimum contact time during xanthation was 4h with a carbon
      disulfide to base material ratio (w/w) of 1.25. Only strong bases like NaOH, KOH
      contributed high copper loadings and the starting liquor was reused twice without
      sacrificing the copper removal capacity of IBX and IWX. Maximum copper loadings
      achieved with IBX and IWX were 26.9+/-0.15 and 27.8+/-0.39 mg/g, respectively.

PMID- 16298525
TI  - Synthesis and structure-activity relationships of a new series of 2alpha
      substituted trans-4,5-dimethyl-4-(3-hydroxyphenyl)piperidine as mu-selective
      opioid antagonists.
AB  - Structure-activity relationships at the 2alpha-position of the piperidine ring of
      the trans-4,5-dimethyl-4-(3-hydroxyphenyl)piperidine mu-opioid antagonist series
      were investigated. This study showed that only small linear alkyl groups (methyl,
      propyl) are tolerated at the 2alpha-position of the piperidine ring of this
      series.

PMID- 16298526
TI  - Syntheses and evaluation of novel fatty acid-second-generation taxoid conjugates
      as promising anticancer agents.
AB  - Polyunsaturated fatty acids such as docosahexaenoic acid (DHA), linolenic acid,
      and linoleic acid were linked to the C-2' position of the second-generation
      taxoids that could overcome MDR caused by overexpressed ABC transporters. The new
      conjugates, tested in vivo, exhibited strong activity against drug-resistant
      colon cancer and drug-sensitive ovarian cancer xenografts in mice. Two of the new
      conjugates, DHA-SB-T-1214 and DHA-SB-T-1213, were found to achieve the total
      regression of drug-resistant and drug-sensitive tumors, respectively, in the
      animal models with substantially reduced systemic toxicity.

PMID- 16298527
TI  - Design, synthesis, and biological evaluation of monopyrrolinone-based HIV-1
      protease inhibitors possessing augmented P2' side chains.
AB  - A series of monopyrrolinone-based HIV-1 protease inhibitors possessing rationally
      designed P2' side chains have been synthesized and evaluated for activity against
      wild-type HIV-1 protease. The most potent inhibitor displays subnanomolar potency
      in vitro for the wild-type HIV-1 protease. Additionally, the monopyrrolinone
      inhibitors retain potency in cellular assays against clinically significant
      mutant forms of the virus. X-ray structures of these inhibitors bound in the wild
      type enzyme reveal important insights into the observed biological activity.

PMID- 16298528
TI  - Discovery of a potent phenolic N1-benzylidene-pyridinecarboxamidrazone selective
      against Gram-positive bacteria.
AB  - As part of a study into antimycobacterial compounds a set of phenolic N1
      benzylidene-pyridinecarboxamidrazones was prepared and evaluated. This report
      describes the unexpected discovery of a potent compound with a pronounced
      selectivity for Gram-positive bacteria over Gram-negative micro-organisms. In
      addition, this compound is active against various drug-resistant Gram-positive
      bacteria.

PMID- 16298529
TI  - Microwave-assisted synthesis of N-alkylated benzotriazole derivatives:
      antimicrobial studies.
AB  - Synthesis and characterization of N-alkylated benzotriazole derivatives 2(a-g)
      bearing pharmaceutically important bioactive substituents and their antimicrobial
      studies in vitro are described. The syntheses of the compounds were achieved by N
      alkylation of the benzotriazole with different bioactive alkyl halides in
      presence of powdered K2CO3 in DMF solution and by microwave irradiation method
      with good yield compared to conventional method. The crystal structure analysis
      shows that compound 4'-benzotriazol-1-yl-methyl-biphenyl-2-carbonitrile 2a
      crystallizes in the space group P1 with cell parameters a = 8.526 (3) A, b =
      12.706 (3) A, c = 7.966 (2) A, alpha = 100.89 (2) degrees , beta = 101.63 (3)
      degrees , gamma = 102.20(2) degrees, Volume = 801.7(4) A degrees , Z = 2 and the
      final R factor is 0.0559 for 6130 reflections with 218 parameters and zero
      restraint. This structure exhibits intermolecular hydrogen bonding. Compounds 2e,
      2a showed significant antimicrobial activity.

PMID- 16298530
TI  - Apoptosis-inducing effect of epolactaene derivatives on BALL-1 cells.
AB  - Epolactaene, a neuritogenic compound in human neuroblastoma SH-SY5Y, induces
      apoptosis in a human leukemia B-cell line, BALL-1. The apoptosis-inducing
      activities of 34 epolactaene derivatives, including those of the newly
      synthesized alpha-alkyl-alpha,beta-epoxy-gamma-lactam derivative and cyclopropane
      derivatives, were also tested. The structure-activity relationships of the
      epolactaene derivatives as an inducer of apoptosis are described. The alpha-acyl
      alpha,beta-epoxy-gamma-lactam moiety as well as the hydrophobicity derived from
      the long alkyl side chain are both important for activity. Compound 1e displayed
      the strongest activity among all the synthesized compounds with an IC50 value of
      0.70 microM.

PMID- 16298531
TI  - Mice lacking alpha-synuclein are resistant to mitochondrial toxins.
AB  - Abnormalities in the function of alpha-synuclein are implicated in the
      pathogenesis of Parkinson's disease (PD). We found that alpha-synuclein-deficient
      mice are resistant to MPTP-induced degeneration of dopaminergic neurons. There
      was dose-dependent protection against loss of both dopamine in the striatum and
      dopamine transporter (DAT) immunoreactive neurons in the substantia nigra. These
      effects were not due to alterations in MPTP processing. We found that alpha
      synuclein-deficient mice are also resistant to both malonate and 3-nitropropionic
      acid (3-NP) neurotoxicity. There was reduced generation of reactive oxygen
      species in alpha-synuclein-deficient mice following administration of 3-NP. These
      findings implicate alpha-synuclein as a modulator of oxidative damage, which has
      been implicated in neuronal death produced by MPTP and other mitochondrial
      toxins.

PMID- 16298532
TI  - Sex differences in cardiac and autonomic response to clinical and experimental
      pain in LBP patients.
AB  - Rehabilitation professionals are currently using heart rate (HR) in order to
      assess the sincerity of effort in certain evaluations. It has been shown that a
      relation exists between HR and pain but no study has measured cardiac response
      during both clinical and experimental pain among a patient population using an
      intra-subject design. Thirty patients with low back pain (LBP) participated in
      this study including 16 men. Clinical pain was induced by applying a postero
      anterior pressure (PA) on a painful lumbar segment for 15 and 30s in order to
      reproduce the patient's typical LBP at an intensity ranging between 50 and
      70/100. Experimental pain was induced with a 15s thermal stimulus at a
      temperature which reproduced the same pain intensity as the 15s PA. For both
      reproduced clinical pain durations, we observed a rise in HR ranging between 8.5%
      and 12.67%. However, unlike men, women's cardiac response failed to show a
      constant rise in HR during the 30s PA. For all subjects, the rise in HR was much
      lower during the experimental pain condition (p<0.001), reaching only 5%. On the
      other hand, galvanic skin responses were significantly higher during the
      experimental pain condition (p<0.001). During this same condition, women also had
      a greater rise in galvanic skin responses than men (p=0.04). Finally, a
      significant correlation was found between both types of pain. These results
      suggest that pain induced during a clinical evaluation will produce a significant
      HR augmentation. However, heart rate variability analysis showed greater
      sympathetic cardiac regulation for men. The sex differences observed in this
      study call for caution when interpreting HR during pain assessment.

PMID- 16298533
TI  - Solid-state 31P CP/MAS and static 65Cu NMR characterization of polycrystalline
      copper(I) dialkyldithiophosphate clusters.
AB  - Polycrystalline tetra-nuclear Cu4[S2P(O-i-C3H7)2]4, hexa-nuclear
      Cu6[S2P(OC2H5)2]6, and octa-nuclear Cu8[S2P(O-i-C4H9)2]6(S) complexes were
      synthesized and analyzed by means of solid-state 31P CP/MAS and 65Cu static NMR
      spectroscopy. The symmetries of the electronic environments around each P-site
      were estimated from the 31P chemical shift anisotropy (CSA) parameters,
      Deltaaniso and eta. The 65Cu chemical shift and quadrupolar splitting parameters
      obtained from the experimental 65Cu NMR spectra of the polycrystalline Cu(I)
      complexes are presented. A solid-state NMR approach for the elucidation of the
      stereochemistry of poly-nuclear Cu(I) dithiophosphate complexes, when the
      structural analysis of the systems by single-crystal X-ray diffraction is not
      readily available, is proposed.

PMID- 16298534
TI  - Cys(x)His(y)-Zn2+ interactions: possibilities and limitations of a simple
      pairwise force field.
AB  - In zinc proteins, the Zn2+ cation frequently binds with a tetrahedral
      coordination to cysteine and histidine side chains. We examine the possibilities
      and limitations of a classical, pairwise force field for molecular dynamics of
      such systems. Hartree Fock and density functional calculations are used to obtain
      geometries, charge distributions, and association energies of side chain
      analogues bound to Zn2+. Both ionized and neutral cysteines are considered. Two
      parameterizations are obtained, then tested and compared through molecular
      dynamics simulations of two small, homologous proteins in explicit solvent:
      Protein Kinase C and the Cysteine Rich Domain (CRD) of Raf, which have two
      Cys3His-Zn2+ groups each. The lack of explicit polarizability and charge transfer
      in the force field leads to poor accuracy for the association energies, and to
      parameters--including the zinc charge, that depend on the number of bound
      cysteines and their protonation state. Nevertheless, the structures sampled with
      the best parameterization are in good overall agreement with experiment, and have
      zinc coordination geometries compatible with related structures in the Cambridge
      Structural Database and the Protein Data Bank. Non-optimized parameters lead to
      poorer structures. This suggests that while a simple force field is not
      appropriate for processes involving exchange between water and amino acids in the
      zinc coordination sphere (e.g. protein unfolding), it can be useful for
      equilibrium simulations of stable Cys3His zinc fingers.

PMID- 16298535
TI  - Clinically masked increases in bronchial inflammation in guideline-treated
      persistent asthma.
AB  - BACKGROUND: Current guidelines generally recommend a combination of inhaled
      corticosteroids and a Beta2-agonist for persistent asthma. The adjustment of anti
      inflammatory therapy in persistent asthma is advised to be guided mainly by the
      presence of symptoms. OBJECTIVE: To investigate whether clinically masked
      increases in bronchial inflammation occur in guideline-treated, persistent asthma
      following allergen exposure. METHODS: After a 4-week steroid-run-in period
      (fluticasone 250 microg twice daily) 48 allergic patients with persistent asthma
      underwent a bronchial challenge with a single dose of allergen, after inhalation
      of salbutamol (400 microg, nebulized dose). FEV1 and sputum markers of bronchial
      inflammation were measured before and after allergen challenge. Furthermore,
      additional rescue-salbutamol usage was recorded following allergen challenge.
      RESULTS: After allergen challenge there was a significant increase in sputum
      eosinophil numbers (geometric mean number x 10(4)/g [95% CI]: 0.5 [0.3; 1.0]
      before, and 2.4 [1.3; 4.2] after challenge, p=0.01). The mean change in FEV1
      between 4 and 8h after challenge relative to baseline was -0.04% [95% CI-2.3;
      2.2], p>0.9. None of the patients took additional rescue salbutamol over 8 h
      after allergen challenge. CONCLUSIONS: Clinically masked increases in bronchial
      inflammation occur in guideline-treated, persistent asthma following allergen
      exposure. This finding underscores the need for additional guides for the
      adjustment of anti-inflammatory therapy in persistent asthma.

PMID- 16298536
TI  - Infectious disease consultations and antibiotic usage in a Turkish university
      hospital.
AB  - OBJECTIVES: The aim of this study was to investigate the various features of
      infectious disease (ID) consultations and the usage of antibiotics in a Turkish
      university hospital. METHODS: A total of 395 consultation requests were recorded
      during a three-year period. RESULTS: The departments most frequently requesting
      the consultation services of the ID department were Orthopedics (29.6%),
      Neurology (18.5%), Cardiology (11.8%) and Internal Medicine (10.4%). The main
      reasons were for diagnosis of unexplained fever (42.3%) and for antibiotic
      modification according to culture results (18%). Diagnoses made by the ID
      consultant were pneumonia (16.7%), urinary tract infections (9.3%), bone and
      joint prosthesis infections (9.1%) and in 15.7% of the investigated patients, no
      infectious focus was determined. It was recognized that the use of antibiotics
      had already been initiated in the great majority of patients (67.1%) before the
      consultation request. While the current therapy was changed in 57.4% of these
      patients, antibiotics were not necessary for 9.8%. CONCLUSIONS: Since the most
      common diagnoses were respiratory and urinary tract or bone and joint prosthesis
      infections, the ID specialists should have detailed knowledge of these problems.
      Usage of antibiotics without ID consultation was prevalent, therefore a
      continuous educational program is a necessity for healthcare workers in the
      hospital.

PMID- 16298537
TI  - Trends in leptospirosis epidemiology in France. Sixty-six years of passive
      serological surveillance from 1920 to 2003.
AB  - OBJECTIVES: The incidence of leptospirosis, a worldwide zoonosis, has
      significantly decreased in Western Europe during the last decades. Our aim was to
      analyse all reliable data collected at the Institut Pasteur from 1920 to 2003 to
      evaluate more precisely the evolution of the incidence of leptospirosis in
      France. METHODS: The passive surveillance system used as early as 1920 allows the
      evaluation of leptospirosis incidence. Serological results inferred from the
      microagglutination procedure were used to evaluate variation in the incidence of
      the disease and the evolution of the Leptospira serogroups involved in the human
      disease. RESULTS: No significant variation either in the number of leptospirosis
      cases or in the incidence of the disease was observed. However, the period of the
      1970s was characterized by a rather low incidence. The weather plays a major role
      by modifying fresh water abundance, rodent populations and human behaviour.
      However the weather's influence is not the sole factor involved in the incidence
      rate. No cyclic variation was evident. CONCLUSION: Although France has the
      highest incidence of leptospirosis in Europe, the analysis of serological data
      collected over 66 years has allowed us to conclude that in France, the incidence
      is slowly decreasing.

PMID- 16298538
TI  - Nosocomial infection rates following cardiothoracic surgery in Iran.

PMID- 16298540
TI  - Ultrasonic pretreatment of liquid NaK metal catalyst for side-chain alkenylation
      of o-xylene with 1,3-butadiene.
AB  - The effects of sonochemical treatment of a NaK eutectic mixture as catalyst on
      the side-chain alkenylation of o-xylene with 1,3-butadiene were studied. The
      parameters studied include ultrasound frequency, insonation time, sonication
      power as well as the reaction temperature. In addition, the effect of N,N,N',N'
      tetramethylethylenediamine (TMEDA) on the reaction was also studied. The results
      showed that sonochemical treatment of this NaK eutectic mixture catalyst resulted
      in excellent conversion (up to 83.16%) under mild conditions. The introduction of
      TMEDA further increased the conversion to 89.4%.

PMID- 16298539
TI  - [Soft tissue sarcoma: role of imaging for initial diagnosis and treatment].
AB  - Soft tissue sarcomas are uncommon heterogeneous group of tumour derived from
      mesenchym. The most common location is the lower extremity, but they can occur in
      the upper extremity, and abdominal and chest walls. The first radiological
      evaluation may include plain films and ultrasonography in viewing to assess the
      probability of soft tissue sarcomas. MRI with contrast is the main modality to
      evaluate these lesions and choose which part of tumour must be biopsied. Computer
      tomography (CT) is secondary used to perform core needle biopsy and detect lung
      metastases. The role of PET begins to be more clear in case of need global
      assessment before radical surgery. A multidisciplinary approach is essential to
      perform rational treatment planning and avoid partial surgery.

PMID- 16298541
TI  - Physiological modelling of agitation-sedation dynamics including endogenous
      agitation reduction.
AB  - Sedation administration and agitation management are fundamental activities in
      any intensive care unit. A lack of objective measures of agitation and sedation,
      as well as poor understanding of the underlying dynamics, contribute to
      inefficient outcomes and expensive healthcare. Recent models of agitation
      sedation pharmacodynamics have enhanced understanding of the underlying dynamics
      and enable development of advanced protocols for semi-automated sedation
      administration. However, these initial models do not capture all observed
      dynamics, particularly periods of low sedative infusion. A physiologically
      representative model that incorporates endogenous agitation reduction (EAR)
      dynamics is presented and validated using data from 37 critical care patients.
      High median relative average normalised density (RAND) values of 0.77 and 0.78
      support and minimum RAND values of 0.51 and 0.55 for models without and with EAR
      dynamics respectively show that both models are valid representations of the
      fundamental agitation-sedation dynamics present in a broad spectrum of intensive
      care unit (ICU) patients. While the addition of the EAR dynamic increases the
      ability of the model to capture the observed dynamics of the agitation-sedation
      system, the improvement is relatively small and the sensitivity of the model to
      the EAR dynamic is low. Although this may represent a limitation of the model,
      the inclusion of EAR is shown to be important for accurately capturing periods of
      low, or no, sedative infusion, such as during weaning prior to extubation.

PMID- 16298542
TI  - Fuzzy logic control for intracranial pressure via continuous propofol sedation in
      a neurosurgical intensive care unit.
AB  - The major goal of this paper is to provide automatically continuous propofol
      sedation for patients with severe head injury, unconsciousness, and mechanical
      ventilation in order to reduce the effect of agitation on intracranial pressure
      (ICP) using fuzzy logic control in a neurosurgical intensive care unit (NICU).
      Seventeen patients were divided into three groups in which control was provided
      with three different controllers. Experimental control periods were of 60min
      duration in all cases. Group A used a conventional rule-based controller (RBC),
      Group B a fuzzy logic controller (FLC), and Group C a self-organizing fuzzy logic
      controller (SOFLC). The performance of the controllers was analyzed by ICP
      pattern of sedation. The ICP pattern of errors was analyzed for mean and root
      mean square deviation (RMSD) for the entire duration of control (i.e., 1h). The
      results indicate that FLC can easily mimic the rule-base of human experts (i.e.,
      neurosurgeons) to achieve stable sedation similar to the RBC group. Furthermore,
      the results also show that a SOFLC can provide more stable sedation of ICP
      pattern because it can modify the fuzzy rule-base to compensate for inter-patient
      variations.

PMID- 16298543
TI  - Comparison of stimulation patterns for FES-cycling using measures of oxygen cost
      and stimulation cost.
AB  - AIM: The energy efficiency of FES-cycling in spinal cord injured subjects is very
      much lower than that of normal cycling, and efficiency is dependent upon the
      parameters of muscle stimulation. We investigated measures which can be used to
      evaluate the effect on cycling performance of changes in stimulation parameters,
      and which might therefore be used to optimise them. We aimed to determine whether
      oxygen cost and stimulation cost measurements are sensitive enough to allow
      discrimination between the efficacy of different activation ranges for
      stimulation of each muscle group during constant-power cycling. METHODS: We
      employed a custom FES-cycling ergometer system, with accurate control of cadence
      and stimulated exercise workrate. Two sets of muscle activation angles
      ("stimulation patterns"), denoted "P1" and "P2", were applied repeatedly (eight
      times each) during constant-power cycling, in a repeated measures design with a
      single paraplegic subject. Pulmonary oxygen uptake was measured in real time and
      used to determine the oxygen cost of the exercise. A new measure of stimulation
      cost of the exercise is proposed, which represents the total rate of stimulation
      charge applied to the stimulated muscle groups during cycling. A number of energy
      efficiency measures were also estimated. RESULTS: Average oxygen cost and
      stimulation cost of P1 were found to be significantly lower than those for P2
      (paired t-test, p<0.05): oxygen costs were 0.56+/-0.03l min-1 and 0.61+/-0.04l
      min-1 (mean+/-S.D.), respectively; stimulation costs were 74.91+/-12.15 mC min-1
      and 100.30+/-14.78 mC min-1 (mean+/-S.D.), respectively. Correspondingly, all
      efficiency estimates for P1 were greater than those for P2. CONCLUSION: Oxygen
      cost and stimulation cost measures both allow discrimination between the efficacy
      of different muscle activation patterns during constant-power FES-cycling.
      However, stimulation cost is more easily determined in real time, and responds
      more rapidly and with greatly improved signal-to-noise properties than the
      ventilatory oxygen uptake measurements required for estimation of oxygen cost.
      These measures may find utility in the adjustment of stimulation patterns for
      achievement of optimal cycling performance.

PMID- 16298544
TI  - TGF-beta as a T cell regulator in colitis and colon cancer.
AB  - TGF-beta is a pleiotropic cytokine with powerful immunosuppressive functions.
      Mice deficient for TGF-beta1 show a dramatic phenotype with severe multiorgan
      inflammation and die shortly after birth. Recent investigations have highlighted
      the role of TGF-beta in suppression of T cell mediated autoimmune inflammation
      and anti-tumor immunity. In addition to its direct anti-inflammatory effects on T
      cells, TGF-beta has been implicated as central regulator of regulatory T cells.
      TGF-beta not only mediates the suppression of effector T cells by Tregs, recent
      evidence also reveals a role for TGF-beta along with TCR stimulation in the
      peripheral induction of regulatory T cells from naive CD4+CD25- cells.

PMID- 16298545
TI  - Home telehealth--current state and future trends.
AB  - OBJECTIVE: The purpose of this paper is to give an overview about the state of
      the art in research on home telehealth in an international perspective. METHOD:
      The study is based on a review of the scientific literature published between
      1990 and 2003 and retrieved via Medline in January/February 2004. All together,
      the abstracts of 578 publications have been analyzed. RESULTS: The majority of
      publications (44%) comes from the United States, followed by UK and Japan. Most
      publications deal with vital sign parameter (VSP) measurement and audio/video
      consultations ("virtual visits"). Publications about IT tools for improved
      information access and communication as well as decision support for staff,
      patients and relatives are relatively sparse. Clinical application domains are
      mainly chronic diseases, the elderly population and paediatrics. CONCLUSIONS:
      Internationally, we observe a trend towards tools and services not only for
      professionals but also for patients and citizens. However, their impact on the
      patient-provider relationship and their design for special user groups, such as
      elderly and/or disabled needs to be further explored. In general, evaluation
      studies are rare and further research is critical to determine the impacts and
      benefits, and limitations, of potential solutions and to overcome a number of
      hinders and restrictions, such as - the lack of standards to combine incompatible
      information systems; - the lack of an evaluation framework considering legal,
      ethical, organisational, clinical, usability and technical aspects; - the lack of
      proper guidelines for practical implementation of home telehealth solutions.

PMID- 16298546
TI  - Prospective study on early virologic response to treatment with interferon alpha
      2b plus ribavirin in patients with chronic hepatitis C genotype 1b.
AB  - To evaluate the predictive value of early virologic response (EVR) of achieving a
      sustained virologic response (SVR), an open, prospective trial including 42
      patients with chronic hepatitis C genotype 1b was performed with directly
      observed 24-week treatment with interferon alpha-2b plus ribavirin. We assessed
      the predictive values of EVR at days 3, 7, 14, and weeks 4, 8, and 12 of the SVR.
      The SVR in an intention-to-treat analysis was 19.0%. Patients who reached SVR
      presented a significantly faster reduction in plasma viral load. Stepwise
      multiple logistic regression analysis of the factors (gender, age, IFN dosage,
      ribavirin dosage, HCV RNA, ISDR, and loss of HCV RNA at week 4) revealed that
      loss of HCV RNA at week 4 was the only independent variable of treatment outcome
      (P=0.0039). A viral load at treatment day 3 above 100kIU/ml, at day 7 above
      50kIU/ml, and at day 14 above 10kIU/ml was 100% predictive for virologic non
      response in all except 1 patient. The cutoff levels for HCV RNA at days 3 and 14
      of treatment were associated with an algorithm of the failure to detect HCV RNA
      after 12 weeks of treatment. In conclusions, a very early virologic response
      assessment could be useful for prediction of later outcome of combination therapy
      in chronic hepatitis C genotype 1b.

PMID- 16298547
TI  - Improvement of cytomegalovirus avidity testing by adjusting the concentration of
      CMV-specific IgG in test samples.
AB  - BACKGROUND: Human cytomegalovirus (CMV) is the most common cause of viral
      intrauterine infection. Primary CMV infection in early pregnancy bears a high
      risk of fetal damage. Accurate measurement of CMV-specific IgG avidity may help
      to improve the serodiagnosis of CMV-infected women by determining the time of
      infection and fetal outcome. OBJECTIVES: To study the performance of the CMV
      avidity assay with the fully automated Vidas analyzer (bioMerieux) as a function
      of the concentration of CMV-specific IgG present in the serum sample. STUDY
      DESIGN: Eighty-two serum samples were investigated from 3 clinical scenarios: 18
      individuals with sera negative for CMV-specific IgG and IgM (control group), 20
      pregnant women (44 samples) containing CMV-specific IgG- and IgM-antibodies
      suggesting acute or recent primary infection and 20 patients with evidence of
      past infection (CMV-IgG positive and CMV-IgM negative). RESULTS: In the group
      with presumed acute or recent primary infection 12 of 44 sera had CMV-specific
      IgG values above 100 arbitrary units (AU, bioMerieux)/ml and in these cases an
      increase in AI was measurable upon dilution of the serum sample. In two cases,
      AI's were shifted towards or above the cut-off value of AI>or=0.8, indicative of
      past infection. Dilution of sera which were CMV-specific IgM positive and had
      specific IgG concentrations of <or=100 AU/ml produced only minor changes in AI.
      In individuals with serology indicative of past infection, dilution effects
      similar to the group of acute or recently infected individuals were observed and
      if CMV-specific IgG was above 100 AU/ml an increase in AI to above or equal to
      the cut-off could only be calculated after serum dilution. CONCLUSIONS: The
      results obtained from undiluted patients' sera with high CMV-IgG concentrations
      indicate that falsely low avidity indices are obtained if these sera are not
      diluted to below an empirically determined CMV-specific IgG concentration. In
      addition, the cut-off value for this commercial CMV-IgG avidity assay should be
      revised.

PMID- 16298548
TI  - Liquid-based hybridization assay with real-time detection in miniaturized array
      platforms.
AB  - An assay for the fluorescent detection of short oligonucleotide probe
      hybridization in miniaturized high-density array platforms is presented. It
      combines hybridization in solution with real-time fluorescent detection, which
      involves measurement of fluorescence increase by means of an induced fluorescence
      resonance energy transfer. The feasibility of this approach using DNA or RNA as a
      target, and short DNA- as well as LNA (locked nucleic acid)-modified
      oligonucleotides as probes is shown. The presented approach could potentially
      contribute to a significant increase in the throughput of large-scale genomic
      applications, such as oligofingerprinting and genotyping, and also reduce
      material consumption.

PMID- 16298549
TI  - A qualitative study of the characteristics and representation of fatigue in a
      French speaking population of cancer patients and healthy subjects.
AB  - The aim of this study was to explore the differences in the representation of
      fatigue between cancer patients and healthy subjects; identify the concepts,
      dimensions and terminology of fatigue specific to patients with cancer-related
      fatigue (CRF) and healthy persons; examine some of the strategies used in illness
      and in health to overcome fatigue. A qualitative research design, using grounded
      theory was used. Twenty-four cancer patients were recruited in outpatients or the
      wards of a cancer institute and 24 healthy subjects among the hospital personnel
      or the investigator's entourage. Data were collected through individual audio
      taped, open-ended interviews. The transcripts of the interviews were reviewed,
      and the participants' responses analysed thematically and grouped into major
      categories and sub-categories. This study demonstrated differences in the
      intensity, variability, duration and temporality of fatigue between patients and
      healthy subjects. Analysis resulted in the categorisation of fatigue into three
      major dimensions, physical, affective and cognitive, common to both patients and
      healthy subjects, although the frequency and occurrence of themes within these
      categories differed slightly in the two groups. A fourth category, distress, was
      identified in the patient group. The linguistic descriptions of fatigue confirmed
      the differing perceptions of fatigue between patients and healthy individuals and
      a heightened concern for the negative aspects of fatigue and suffering among
      patients. A four-step conceptual model for fatigue was developed explaining the
      different stages in individual responses to fatigue.

PMID- 16298550
TI  - A study to assess the existence of the symptom cluster of breathlessness, fatigue
      and anxiety in patients with advanced lung cancer.
AB  - The purpose of this small-scale study was to assess the existence of a symptom
      cluster involving breathlessness, fatigue and anxiety in patients with advanced
      lung cancer undergoing palliative radiation. A convenience sample of 27 patients
      were asked to complete a set of 100mm horizontal visual analogue scales (VAS)
      measuring the intensity of anxiety, breathlessness and fatigue at 3 points in
      time: 1 day prior to palliative radiotherapy (RT) (baseline, T0), and at week 3
      (T1) and week 6 (T2) after the commencement of the RT. The prevalence of the 3
      symptoms ranged from 59% to 96%. At baseline the median intensity of symptoms was
      mild, becoming progressively worse at T1 and T2. The correlations between the 3
      symptoms were moderately strong at T1 and T2 (r=0.49-0.75). The proposed symptom
      cluster had high internal consistency across T0-T2. These data support the notion
      that the symptoms--breathlessness, fatigue, and anxiety--may be viewed as a
      symptom cluster. The high prevalence and moderate intensity of the symptom
      cluster demonstrates a need for an intervention to manage these symptoms
      simultaneously.

PMID- 16298551
TI  - The etiology of sepsis: turned inside out.
AB  - The sepsis syndrome is thought to occur when microbial products activate Toll
      like receptors stimulating widespread inflammation, in turn causing organ
      failure, shock and death. However, recent discoveries reveal that: (i) not only
      microbial substances but also endogenous molecules can trigger Toll-like
      receptors; (ii) Toll-like receptor-4, the endotoxin receptor, is constitutively
      suppressed; and (iii) the first step in sepsis could be the release of Toll-like
      receptor-4 from suppression. These discoveries suggest that endotoxin might not
      always initiate the sepsis syndrome and they explain why anti-endotoxin therapies
      fail. The discoveries also suggest new therapeutic targets - endogenous agonists
      and Toll-like receptor regulators - for treatment of sepsis.

PMID- 16298552
TI  - Is sense of coherence a pathway for improving the quality of life of patients who
      grow up with chronic diseases? A hypothesis.
AB  - A recent study indicated that the quality of life in adult patients with
      congenital heart disease was better than that of their healthy counterparts. A
      possible explanation for this is that these patients have a stronger sense of
      coherence than do their healthy counterparts. This enhanced sense of coherence
      develops in childhood through the successful application of generalized
      resistance resources. Here, we advance the hypothesis that sense of coherence may
      be a potential pathway for improving the quality of life in patients who grow up
      with a chronic health condition. This hypothesis needs to be tested in long-term
      longitudinal studies. If such studies can confirm the hypothesis, SOC can be an
      important target for interventions in childhood to improve patients' quality of
      life during adulthood.

PMID- 16298553
TI  - The binding of sera of patients with SLE to bacterial and mammalian DNA.
AB  - Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease
      characterized by antibodies to DNA (anti-DNA). Although these antibodies have
      features of antigen drive, the source of this DNA is not defined. To assess the
      potential role of foreign and self-DNA as driving antigens, the specificity of
      SLE sera for bacterial and mammalian DNA was evaluated. Micrococcus lysodeikticus
      (MC) and calf thymus (CT) DNA were tested as antigens, with absorption on CT DNA
      columns used to identify antibodies to antigenic sites on the two DNA. Among 9
      sets of longitudinal sera tested, all showed binding to both DNA, and none showed
      exclusive or predominant binding to CT DNA. With absorbed sera, antibodies could
      be distinguished in terms of cross-reactive or selective binding to the DNAs.
      These findings suggest that anti-DNA antibodies vary in specificity and are
      consistent with a role of both foreign and self-DNA in anti-DNA induction.

PMID- 16298554
TI  - Urological surgical techniques.
AB  - Urinary tract injuries during gynaecological surgery are increasing with the
      advent of more complex and laparoscopic techniques; ureteric and bladder injuries
      are the most common. Adequate knowledge of the anatomy will help avoid some
      problems, but prompt recognition during surgery offers the best chance of
      treatment without long-term compromise. When the problems are not recognised
      during surgery, various techniques can be used to effect repair. Surgery for
      stress incontinence has undergone many changes in technique in recent years. Any
      procedure needs to combine a low morbidity with high long-term success rates.
      Colposuspension has been the 'gold standard' for many years, against which other
      techniques are judged. A laparoscopic approach has reduced hospital stay,
      although with increased morbidity. The tension-free vaginal tape technique is now
      widely employed as the first-line procedure. It is a relatively easy technique to
      learn, with a good success rate and low morbidity; long-term results are still
      awaited. This chapter deals with two aspects of urogynaecological surgery. The
      first section reviews urinary tract injuries occurring during gynaecological
      surgery. In the second section we look at recent developments in surgery for
      urinary stress incontinence.

PMID- 16298555
TI  - Response to commentaries on Koppel et al.

PMID- 16298556
TI  - WaveRead: automatic measurement of relative gene expression levels from
      microarrays using wavelet analysis.
AB  - Gene expression microarrays monitor the expression levels of thousands of genes
      in an experiment simultaneously. To utilize the information generated, each of
      the thousands of spots on a microarray image must be properly quantified,
      including background correction. Most present methods require manual alignment of
      grids to the image data, and still often require additional minor adjustments on
      a spot by spot basis to correct for spotting irregularities. Such intervention is
      time consuming and also introduces inconsistency in the handling of data. A fully
      automatic, tested system would increase throughput and reliability in this field.
      In this paper, we describe WaveRead, a fully automated, standalone, open-source
      system for quantifying gene expression array images. Through the use of wavelet
      analysis to identify the spot locations and diameters, the system is able to
      automatically grid the image and quantify signal intensities and background
      corrections without any user intervention. The ability of WaveRead to perform
      proper quantification is demonstrated by analysis of both simulated images
      containing spots with donut shapes, elliptical shapes, and Gaussian intensity
      distributions, as well as of standard images from the National Cancer Institute.

PMID- 16298557
TI  - Improved HPLC method for the simultaneous determination of allantoin, uric acid
      and creatinine in cattle urine.
AB  - An HPLC procedure developed for the rapid and simultaneous determination of
      purine derivatives (PD) in ruminants' urine was investigated, since the adoption
      of a single method for the simultaneous detection of PD and creatinine was not
      carried out due to elution of polar co-extractives and also due to overlapping of
      the peaks of allantoin and creatinine. The experimental conditions chosen in the
      present study avoid the presence of chemically competitive compounds and afford a
      good separation of the peaks of allantoin and creatinine. The recoveries of the
      standard compounds added to urine samples were 94-104%. This method can be
      proposed as a possible reference method for the estimation of allantoin, uric
      acid and creatinine in cattle urine.

PMID- 16298558
TI  - Effects of dissociated glucocorticoids on OPG and RANKL in osteoblastic cells.
AB  - Glucocorticoids are effective anti-inflammatory and immunosuppressive agents, but
      their use is often associated with debilitating side effects such as
      glucocorticoid-induced osteoporosis. Newly developed glucocorticoid analogues
      such as the so-called dissociated glucocorticoids are potent immunosuppressants
      and have the potential for fewer side effects. The effects of these new analogues
      on osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) in
      osteoblastic cells have not been studied. OPG and RANKL are osteoblast-derived
      proteins pivotal to the regulation of bone mass. RANKL stimulates bone resorption
      by increasing osteoclast differentiation, activation and survival. OPG is the
      decoy receptor for RANKL and thus inhibits bone resorption. Here, we show that
      dexamethasone, prednisolone, deflazacort and the dissociated glucocorticoids,
      RU24858, RU40066, RU24782, AL438-F1 and ZK216348 significantly inhibit OPG
      production in two human osteoblastic cell lines (MG63 and hFOB). The potency for
      OPG inhibition was ligand and cell-type specific. In both cell types,
      dexamethasone and prednisolone were the most potent ligands inhibiting OPG
      production with IC(50)s of approximately 0.1 nM and 10 nM respectively. In MG63
      cells, deflazacort and the RU compounds were the next most potent ligands
      followed by AL438-F1 and ZK216348. In hFOB cells, however, the RU compounds were
      the least potent ligands with an IC(50) 74 times higher than in MG63 cells. In
      contrast, the level of maximum inhibition or effectiveness of OPG inhibition did
      not vary between cell types but did vary according to the ligand. Dexamethasone,
      prednisolone, deflazacort and the RU compounds all inhibited OPG production by a
      maximum of approximately 70-80%, whereas AL438-F1 and ZK 216348 inhibited OPG
      production by a maximum of only 40-50% at 1 microM. All of the dissociated
      glucocorticoids and deflazacort were poor stimulators of RANKL gene expression
      stimulating by only approximately 1-3-fold compared to 7-fold by prednisolone.
      These data demonstrate that deflazacort and the dissociated glucocorticoids are
      weak stimulators of the RANKL:OPG ratio compared to prednisolone. Therefore,
      these compounds have the potential to cause less bone loss than that seen with
      prednisolone, though this was not investigated here.

PMID- 16298560
TI  - Selected activities in Scandiatransplant.
AB  - Scandiatransplant is the Nordic organ exchange organization. It has existed for
      35 years and it is owned by all organ transplantation hospital departments in the
      five Nordic countries--Denmark, Finland, Iceland, Norway, and Sweden. The use of
      living organ donors for kidney transplantation has become a more common procedure
      not only in Norway but also in Sweden and Denmark. For the first time, in 2003,
      one transplant center performed relatively more living donor kidney
      transplantations than with deceased donors. The overall organ transplant activity
      reveals a remarkably stable situation in the area covered by Scandiatransplant.
      Scandiatransplant as an organ exchange organization has changed from a solely
      kidney exchange organization to an organization in which the more immediate vital
      organs as liver and heart are exchanged more commonly than kidneys.

PMID- 16298561
TI  - Kidney transplantation from 1119 deceased donors in Finland, 1991 to 2003: impact
      of donor factors.
AB  - We assessed the effect of donor factors on the recovery and quality of cadaveric
      kidney transplant function. During 1991 to 2003, 2006 kidney grafts were derived
      from 1119 heart-beating donors in Finland. The annual mean age of donors
      increased from 33 to 46 years, with a significant decrease in the proportion of
      high-energy trauma and gunshot wounds and with an increased proportion of donors
      with coronary disease, hypertension, or cardiopulmonary resuscitation and
      surgical/radiological interventions before death. The transplant team's share of
      kidney retrievals increased from 50% to nearly 100%. In uni- and multivariate
      analyses all these factors had significant effects on the onset and quality of
      early graft function; however, this effect practically vanished by 1 year
      posttransplant. Of all studied donor factors, only donor cytomegalovirus (CMV)
      status significantly affected long-term survival, with donor CMV-positive grafts
      having 5% worse survival at 5 years. The 1-year graft survival improved from
      90.9% to 96.2% and mean 1-year creatinine decreased from 121 micromol/L to 109
      micromol/L during these 13 years, showing that the worsening trends in donors
      quality were compensated by improvements in other aspects of the process.

PMID- 16298562
TI  - Substantial increase in cadaveric organ donors in hospitals implementing the
      donor action program in Finland.
AB  - The results of solid organ transplantation have improved during the last decade.
      Five-year patient survivals over 80% and graft survivals over 70% are common in
      many transplant centers. Also, quality-of-life assessments show that not only
      adults but even small children have a good quality of life after successful organ
      transplantation. Furthermore, transplantation programs have proved to be cost
      effective. However, the organ shortage is a worldwide problem, which has in many
      countries led to prolonged waiting times, deaths on the waiting list, increased
      living related donations, acceptance of lower-quality organs, and in some
      instances even commercialization of the organ supply. Thus, it is extremely
      important to find strategies that increase the number of cadaveric organs for
      donation. In Finland organ transplantation is concentrated in one center with
      about 250 transplantations of different organs performed annually. The number of
      patients needing a new cadaveric organ is steadily increasing, but the number of
      donors has remained the same during the last decade. To improve cadaveric organ
      procurement the Donor Action (DA) program, which consists of a Hospital Attitude
      Survey and a medical records review performed by the donor hospital, has proved
      to increase the number of cadaveric donors. We introduced the DA program in
      Finland in 2000. Here in we report the results of this program in terms of its
      impact on the availability of cadaveric donors.

PMID- 16298564
TI  - Estimating the organ donor potential in Denmark: a prospective analysis of deaths
      in intensive care units in northern Denmark.
AB  - To estimate the organ donor potential in Denmark we conducted a prospective
      registration of deaths in all intensive care units (ICUs), counting 15 ICUs and
      two neurosurgical ICUs in the four northern Danish counties, which cover a
      population of 1.64 million inhabitants or 30% of the Danish population. From
      September 1, 2000 till August 31, 2002, all deaths in the ICUs in 15 hospitals
      were recorded. Each case was evaluated locally postmortem with respect to medical
      suitability to organ donation. A total of 1655 deaths were recorded,
      corresponding to 504 deaths per million population per year (PMP). Median age was
      70 years (0 to 99 years), 52% were more than 70 years, and 22% more than 80 years
      of age. The cause of death was cerebral lesion in 18% of the cases (neurosurgical
      ICUs: n = 182; ICUs: n = 110). By thorough medical record examination, the number
      of potential donors was estimated to be 169, corresponding to 51 PMP. The cause
      of death was cerebral lesion in 96% of the potential donors. Organ donation was
      performed in 43 cases (32 from neurosurgical ICUs and 11 from ICUs) or 13.1 PMP.
      Thus, 25% of the potential became organ donors. The major reason for nondonation
      was refusal from the relatives. Out of 127 questioned, the relatives refused in
      62 cases (49%). By comparison, 74% of the general Danish population are willing
      to donate organs after death. The rate of nondetection of potential donors by the
      hospital staff could be estimated to 22%. In conclusion, the organ donor
      potential may allow for improvement in donation rates. An increased effort for
      donor hospitals is warranted. The motives for refusal by the relatives need
      elucidation.

PMID- 16298563
TI  - Attitudes, knowledge, and proficiency in relation to organ donation: a
      questionnaire-based analysis in donor hospitals in northern Denmark.
AB  - The aim of this study was to assess knowledge, attitudes, and proficiency in
      relation to organ donation among staff members of intensive care units (ICUs) in
      donor hospitals, and possibly identify areas for improvement. The investigation
      was carried out as a collaboration between the transplant center and appointed
      key persons in all 17 ICUs in 15 hospitals in northern Denmark. A total of 1168
      structured questionnaires were distributed to the health care professionals in
      the ICUs in the region; 689 were returned, giving a response rate of 59%. In
      general, there is a positive attitude among health care professionals toward
      organ donation. However, a considerable fraction of 11% declares to be against
      organ donation. Only 49% of the ICU health care professionals are willing to
      donate their own organs after death. By comparison, 74% of the general Danish
      population are willing to donate organs after death. Doctors are more positive
      toward organ donation than the nursing staff. Thus, 95% of the doctors are
      positive to organ donation compared to 81% of the nurses; 70% of the doctors will
      donate own organs after death compared to 45% of the nurses. Further, the survey
      demonstrates as expected a significant lack of experience in organ donation. Our
      data show a considerable need for more education and training, especially on how
      to inform and support the donor relatives and how to identify potential donors.
      The survey also discloses a substantial need for information regarding the
      results of transplantation.

PMID- 16298565
TI  - Results of a multilateral approach to donation-transplantation process in Hungary
      in the past 2 years.
AB  - Hungarotransplant Public Service Corporation, the national organ exchange
      organization, was established in 2001. The assessment of donation- and
      transplantation-related data allows the evaluation of the current situation and
      future trends. The donor reports show involvement of new hospitals and an
      increase in reported donors. These results are due to a new centralized organ
      referral system implemented by Hungarotransplant, employment of donation links in
      donor hospitals, training for key persons in intensive care units, and
      implementation of a Donor Action program, generating frequent and positive media
      attention. In 2002 the number of realized cadaveric donors increased by 21% and
      remained stable in 2003 despite the further increase in referrals. In 2002 the
      number of heart transplants remained the same, and liver transplant activity
      declined. In contrast, in 2003 the heart transplant activity rose by 33% and
      liver transplant activity by 82%. The multiorgan donation rate and the total
      number of transplanted organs have increased continuously. Our data demonstrate
      that organized multilateral efforts resulted in an immediate improvement in
      donation-transplantation activity in Hungary. However, the role of factors other
      than the shortage of organs, such as capacity problems and limited financial
      resources, are also highlighted.

PMID- 16298566
TI  - Variation in organ donation in northeastern England 1986 to 2003.
AB  - Renal transplantation is established as the best form of renal replacement
      therapy, but demand for kidneys exceeds supply from cadaveric donations. It is
      therefore important to make the best use of the pool of potential cadaveric organ
      donors. Donation rates are to a large extent dependent on public opinions, which
      may be influenced by external events. In northeast England from 1986 to 2003,
      there was a potential pool of 1170 brain stem-dead donors, of whom 190 (16%)
      could not be retrieved due to relatives' objections. From 1998 to 2003 we were
      referred 90 potential non-heart-beating donors, of whom relatives refused
      donation in 10 (11%). A major reason for not retrieving organs from a potential
      donor has been lack of consent from the relatives. Refusals appear to vary year
      by year and are consistently lower for non-heart-beating donors. This therefore
      raises the possibility that negative or positive media publicity plays a role in
      this variation.

PMID- 16298567
TI  - Does donor cardiopulmonary resuscitation time affect outcome in uncontrolled non
      heart-beating donor renal transplants?
AB  - Uncontrolled non-heart-beating donors offer the opportunity to significantly
      expand the potential pool of kidney donors but are associated with a variable
      duration of cardiopulmonary resuscitation (CPR), where cardiac output is only 30%
      to 40% of normal. We were concerned that prolonged CPR would adversely affect the
      function of transplanted kidneys. In our series of 46 uncontrolled donors the
      mean duration of CPR was 60 minutes, which also represents a realistic cutoff
      point for CPR duration. Taking a cutoff point of 60 minutes, we found no
      differences in kidney discard rates following viability assessment, primary
      nonfunction rate, or duration of delayed graft function. We therefore conclude
      that if formal viability assessment is performed, kidneys may be retrieved from
      uncontrolled non-heart-beating donors irrespective of duration of CPR.

PMID- 16298568
TI  - Anti-vimentin antibody detection in recipients of heart-beating and non-heart
      beating donor kidneys.
AB  - Alternative donor sources include non-heart-beating donors (NHBDs). There donors
      have been exposed to significant ischemia, so that it is common to utilize
      machine perfusion to either improve the organs or at least assess their
      viability. Both prolonged warm ischemia and machine perfusion can potentially
      damage the vascular endothelium, thereby exposing vimentin to antigenic
      recognition. The aim of this study was to determine whether anti-vimentin
      antibodies could be detected in the blood of renal transplant recipients at
      specific time points after transplant and whether they could be related to the
      donor source. Fifty-one recipients of NHBD kidneys were compared to 52 recipients
      of heart-beating donor (HBD) kidneys. All recipients had similar anti-vimentin
      levels pretransplant. However, at 1 month those kidneys from Maastricht category
      II NHB donors showed significantly higher levels. At 6 months both Maastricht
      category II and category III NHB donor recipients displayed significantly higher
      levels than recipients of HBD kidneys.

PMID- 16298569
TI  - Do recipients of kidneys from donors treated with streptokinase develop anti
      streptokinase antibodies?
AB  - Streptokinase is used for preflush for non-heart-beating donors (NHBDs) in our
      center. The aim of this study was to evaluate whether the use of thrombolytic
      streptokinase results in the production of anti-streptokinase antibodies in the
      recipients after renal transplantation. Recipient sera taken prior to and at 1
      and 6 months posttransplant were tested for the presence of antibodies to
      streptokinase using an enzyme-linked immunosorbent assay assay. No differences
      were detected between a group of 18 recipients who had kidneys from thrombolytic
      treated NHBDs and a further group of 18 who received NHBD kidneys without such
      treatment.

PMID- 16298570
TI  - Oxygenated machine perfusion preservation of predamaged kidneys with HTK and
      Belzer machine perfusion solution: an experimental study in pigs.
AB  - The objective of the present study was to evaluate the recently proposed aerobic
      machine preservation with the noncolloidal HTK solution by comparison with the
      colloidal Belzer machine perfusion solution (MPS) after procurement of marginal
      kidneys from non-heart-beating donors. Kidneys were harvested 40 minutes after
      cardiac arrest in German Landrace pigs and subjected to 18 hours of oxygenated
      hypothermic machine perfusion with either Belzer MPS or modified HTK via the
      renal artery (Psys < 40 mm Hg). During machine perfusion transrenal flow was
      approximatively twofold higher and calculated oxygen uptake was increased by 30%
      using the colloidal Belzer MPS, but overall enzyme release was comparable in both
      groups. After heterotopic transpantation with bilateral nephrectomy of the
      recipient, there were no differences with respect to initial tissue perfusion in
      vivo (evaluated by laser Doppler flowmetry) as well as urine production and
      median serum levels of urea or creatinine over 1 week of follow-up between grafts
      perfused with HTK or Belzer MPS. In conclusion, provision of oxygen during
      storage is possible by low-flow perfusion with HTK as with Belzer MPS.

PMID- 16298571
TI  - Impact of mycophenolate mofetil intolerance on early results of kidney
      transplantation.
AB  - From 1992 to 2003, 407 kidney transplantations were performed on 403 patients
      using cyclosporine (CyA) or tacrolimus (Tac), mycophenolate (MMF), and steroid
      immunosuppression. Patient records examined for adverse events (AE) and MMF dose
      reductions or discontinuations during 100 days posttransplant were correlated
      with data on rejections, graft function, and survival. AEs occurred in 79.1% of
      transplantations. Gastrointestinal (GI) symptoms, infections, and cytopenias were
      common. Surprisingly, in 50% of all transplantations serum alanine transferase
      (ALAT) was elevated, among 21% the change was over three times the upper limit of
      normal. Patients with delayed graft function showed increased incidences of GI
      symptoms and thrombocytopenias. There were more ALAT increases and
      thrombocytopenias in patients on CyA and more GI symptoms in patients on Tac. In
      34% of transplantations, the MMF dose was reduced or discontinued. In CyA
      patients with MMF reduction by day 21, rejection incidence during the subsequent
      21 days was 10% versus 0.6% in patients with full-dose MMF until day 21 (P <
      .002). Among Tac patients no increased rejection frequency was seen after
      reducing MMF.

PMID- 16298572
TI  - Should kidneys from older cadaveric donors be age-matched to the recipient?
AB  - Persistent shortage of kidneys for transplantation has forced most transplant
      centers to include procurement and use of kidneys from older donors. It is not
      clear whether the optimal use of these kidneys involve age-matching to the
      recipient. The aim of this study was to evaluate the clinical outcome of older
      cadaveric kidneys (>60 years), transplanted to young recipients (<50 years) and
      older recipients (>60 years). From 1989 through 2002, 252 first kidney grafts
      were procured from donors above the age of 60; 149 of the recipients to these
      grafts were above 60 years and 45 recipients were below 50. Minimum follow-up
      time was 12 months. Variables for waiting time to transplantation, DR mismatches,
      PRA, dialysis prior to transplantation, episodes of acute rejection, number of
      steroid-resistant rejections, creatinine levels, cold ischemia time, and causes
      of graft loss did not differ between the two groups. There was no significant
      difference in graft survival for young and older recipients receiving kidney from
      donors above 60 years of age. Graft survival at 1 year for young recipients was
      90% and for older recipients 93% (NS). Five-year graft survival was 72% and 79%,
      respectively (NS). However, there was a significant positive effect on long-term
      graft survival if the donor kidney was less than 50 years. From our data, there
      is no evidence that age-matching of older donors has any beneficial effect on
      graft survival in kidney transplantation.

PMID- 16298573
TI  - Audit of diabetes in a renal transplant population.
AB  - AIMS: To determine the prevalence of diabetes and its glycemic control in the
      renal transplant population of northeast England (Newcastle, Sunderland,
      Middlesborough, and Carlisle). METHODS: All renal transplant notes in northeast
      England were reviewed. Data on patient details, type of diabetes, time of onset
      of diabetes, diabetes medications, time of insulin commencement, date of renal
      transplant, immunosuppressive medications, and HbA(1C) were recorded. RESULTS:
      Living renal transplant patients (n = 1073) transplanted between March 1982 and
      November 5, 2003 were identified. One hundred and nine (10.2%) patients had
      diabetes, of whom 39 were type 1 and 70 were type 2. Median HBA(1C) in patients
      with type 1 diabetes on tacrolimus was 10.1% +/- 1.94% (SD) versus 7.8% +/- 1.98%
      (SD) for patients not on tacrolimus. Among patients with type 2 diabetes, 25 had
      diabetes prior to transplant and 45 (4.5%) developed posttransplant diabetes
      (PTDM). Those who developed PTDM and were taking tacrolimus were more likely to
      require insulin for blood glucose control (0.39 U/kg/24 hours vs 0 U/kg/24 hours;
      P = .05) compared to those not on tacrolimus. Both type 1 and type 2 diabetics on
      tacrolimus showed better preservation of renal function as measured by mean serum
      creatinine (type 1: 145 +/- 53 vs 196 +/- 74, P = .02; type 2 pretransplant: 159
      +/- 73 vs 172 +/- 59, P = .35; type 2 posttransplant: 123 +/- 35 vs 167 +/- 63, P
      = .01). CONCLUSIONS: Tacrolimus use in renal transplant patients with diabetes
      appeared to be associated with more problematic blood glucose control; however,
      it seemed to be better at preserving renal function. Intensive blood glucose
      monitoring is recommended for this group.

PMID- 16298574
TI  - ABO-incompatible kidney transplantation and rituximab.
AB  - We have designed a protocol for ABO-incompatible kidney transplantations based on
      antigen-specific immunoadsorption rather than plasmapheresis to remove anti-A or
      anti-B antibodies and with a Prograf/Cellcept/prednisolone protocol using
      rituximab rather than splenectomy to prevent rebound antibodies. Twelve patients
      have successfully received transplants with this protocol. The ABO-antibodies
      were readily removed by the antigen-specific immunoadsorption and maintained at a
      low-level posttransplantation. There were no side effects. All patients have
      normal renal transplant function with a follow-up of 1 to 34 months.

PMID- 16298576
TI  - Cardiovascular risk assessment scoring system for the determination of
      cardiovascular mortality in renal transplant patients.
AB  - It is well known that the greatest risk for mortality post-renal transplant is
      cardiovascular death. We compared a modified cardiac risk assessment system among
      renal transplant patients who subsequently died versus the group that survived.
      There was a good correlation between the low, medium, and high scores with
      survival. The deceased group had significantly greater cardiovascular scores than
      case controls.

PMID- 16298575
TI  - Refractory acute renal allograft rejection successfully treated with
      photopheresis.
AB  - INTRODUCTION: Acute rejection episodes still occur in spite of modern
      immunosuppressive protocols. We present seven patients with biopsy-proven acute
      rejections after kidney transplantation refractory to repeated pulses of high
      dose steroids and antithymocyte globulin (ATG) or OKT-3, but responsive to
      photopheresis therapy. METHODS: Photopheresis is a nontoxic immunomodulatory,
      apheresis-based treatment with no general immunosuppressive action. Rather, it
      suppresses specific pathogenic T-cell clones. During photopheresis mononuclear
      leukocytes are collected from the patient using centrifugation technique, treated
      with a photosensitizing agent, irradiated, and subsequently retransfused.
      RESULTS: All patients tolerated the treatment well, with no notable side effects.
      At the 12-month follow-up the median creatinine had decreased to 161 mumol/L
      compared to 282 mumol/L at the start of photopheresis and at the last follow-up
      12 to 43 months after transplantation all patients still had functioning grafts.
      In five of the seven cases there had been a significant improvement in renal
      function, whereas in two of the patients the renal function remained stable but
      without a decrease in creatinine. CONCLUSIONS: It is our experience that the
      prognosis for renal allografts with acute rejection unresponsive to conventional
      antirejection treatment (ie, repeated pulses of methylprednisolone and ATG or OKT
      3) is very poor. Therefore, we conclude that the photopheresis treatment
      contributed to the favorable outcome in this small group of patients. We are
      presently designing a prospective randomized study to further evaluate the effect
      of photopheresis after renal transplantation.

PMID- 16298577
TI  - A simple cardiovascular risk score can predict poor outcome in NHBD renal
      transplantation.
AB  - A simple cardiovascular risk score used in our center to plan cardiovascular
      workup for renal transplantation can predict outcome in non-heart-beating donor
      (NHBD) renal transplantation. Patients in the higher risk group, with a score of
      >12 out of a maximum of 36 are likely to have a longer duration of delayed graft
      function, poorer glomerular filtration rate at 6 months, and inferior graft and
      patient survival, together with an relative rate of graft loss within 60 days of
      >4 (P = .053). Although a high cardiovascular risk score should not be regarded
      as a contraindication to NHBD transplantation, the score can be used to
      facilitate recipient selection.

PMID- 16298578
TI  - The granule exocytosis and Fas/FasLigand pathways at the time of transplantation
      and during borderline and acute rejection of human renal allografts.
AB  - Cytotoxic lymphocytes induce target cell death by the granule exocytosis
      mechanism in which perforin and granzyme B induce target cell lysis, and ligation
      of the Fas-FasLigand, which results in apoptosis. The purpose was to detect the
      level of activation of cytolytic pathways at the time of renal transplantation
      and during acute rejection. We investigated 119 biopsies obtained at
      transplantation from 100 deceased donor allografts and 19 living donor allografts
      as well as 45 allograft biopsy specimens collected from recipients because of a
      clinical suspicion of an acute rejection episode. Total RNA was isolated and
      transcribed to cDNA. To measure mRNA encoding perforin, granzyme B, and FasLigand
      by real-time quantitative, polymerase chain reaction we used oligonucleotide
      primers in a LightCycler equipment with cyclophilin B as the housekeeping gene.
      At the time of transplantation, the transcript expression levels of perforin and
      granzyme B were the same in the biopsies from deceased and living donors. During
      acute rejection episodes (n = 10), perforin (P < .01), and granzyme B levels (P <
      .05) were significantly up-regulated. In cases of suspected rejection (n = 12),
      both the clinical picture and the effector gene responses were heterogeneous. The
      FasLigand expression was up-regulated during acute rejection episodes (n = 8)
      compared with the time of transplantation, but the change was not significant. In
      conclusion, brain death did not seem to influence the granule exocytosis pathway
      in the kidney. The cytolytic effector pathways are up-regulated in renal
      allograft tissue in acute rejection episodes.

PMID- 16298579
TI  - Chronic cyclosporine nephrotoxicity: a pig model.
AB  - Cyclosporine A (CsA) is one of the keystones in immunosuppressive treatment after
      solid organ transplantation, despite its major side effects such as
      nephrotoxicity. The chronic nephrotoxic effects of CsA seen in humans have been
      difficult to reproduce in small-animal models. The aim of the present study was
      to examine the chronic nephrotoxicity produced by therapeutic dosages of CsA in a
      pig model. Among 11 Gottingen minipigs included in the study, three died,
      yielding data from five animals given CsA (10 mg/kg/d, orally) for 6 months, and
      three controls. Body weight, blood pressure, glomerular filtration rate (GFR) by
      plasma clearance of (51)Cr-ethylenediamine-tetraacetic acid, CsA concentration,
      serum creatinine, and other values were measured every 5 weeks. Our results
      showed that the whole blood trough CsA levels were lower in pigs than in humans
      treated with similar CsA doses. Renal biopsies, which were obtained successfully,
      except one case of macroscopic hematuria, showed no histological changes in the
      kidney. No significant increase in serum creatinine or blood pressure was
      observed. Surprisingly, there was a significant increase in GFR during CsA
      treatment. We conclude that the pig model displays a hyperfiltration that
      warrants further investigation.

PMID- 16298580
TI  - Intrarenal blood oxygenation and renal function measured by magnetic resonance
      imaging during long-term cyclosporine treatment.
AB  - Treatment with cyclosporine (CsA) markedly affects the renin-angiotensin
      aldosterone system in parallel with an increase in the net tubular reabsorption
      or a decrease in secretion. Since tubular reabsorption is closely linked to
      medullary oxygen consumption, the aim of the present study was to investigate the
      intrarenal oxygenation and renal function in response to CsA. Six mini Gottingen
      pigs were treated with CsA (10 mg/kg/d) for 6 months. The intrarenal oxygenation
      was indirectly measured as R2* obtained with a multiecho gradient-echo magnetic
      resonance imaging (MRI) sequence. Single-kidney renal blood flow (skRBF) was
      measured by a velocity-sensitive gradient-echo MRI sequence. Relative single
      kidney glomerular filtration rate (rskGFR) was derived from the MRI time-activity
      curve in response to an intravenous bolus of Gd-DTPA (0.05 mmol/kg). The present
      study showed that administration of CsA increased the medullary R2* (23.1 Hz vs
      19.0 Hz, P = .002), whereas R2* was slightly increased in the renal cortex (13.3
      Hz vs 12.3 Hz, P = .012). In parallel, rskGFR increased significantly (47.2
      mL/min vs 19.8 mL/min, P = .005) but skRBF was unchanged (197.6 mL/min vs 202.5
      mL/min, P > .05). The increased R2* in the renal medulla indicated that CsA
      augments the tubular reabsorption of water, leading to increased oxygen
      consumption. The supply of oxygen to the kidney was, however, maintained during
      treatment with CsA as suggested by an unchanged renal blood flow. The increased
      tubular reabsorption was compensated for by an elevated glomerular filtration
      rate.

PMID- 16298581
TI  - Does chronic low-dose treatment with cyclosporine influence the brain? A
      histopathological study in pigs.
AB  - Twenty percent of the patients immunosuppressed with cyclosporine A (CsA) develop
      neurological side effects such as tremor, paresthesias, headache, seizures,
      visual disorders, paresis, and coma-CsA encephalopathy. The encephalopathy
      resolves on CsA discharge; autopsies of recovered patients are normal.
      Characteristic lesions are seen on magnetic resonance imaging (MRI) during the
      period of encephalopathy. MRI of asymptomatic patients receiving CsA as well as
      most recovered patients are normal. Several theories of pathogenesis have been
      proposed, but none has been firmly established. The current placebo-controlled
      study, blinded to the investigator, was accordingly initiated to elucidate
      histopathological changes in the brain. Twelve adult Gottingen minipigs were
      randomized into two groups treated with either low-dose CsA (10 mg/kg/d) or no
      treatment for 6 months. Behavior, blood pressure, and blood parameters were
      measured throughout the study. All animals had a cerebral MRI before sacrifice.
      Three control pigs and one CsA-treated pig died during observation and were
      excluded from the study. None of the remaining eight pigs displayed behavioral
      signs or MRI-visible lesions characteristic of CsA encephalopathy. The brains
      appeared all normal on the gross pathological examination, but microscopy
      revealed perivascular, meningeal, and neuronal tissue infiltration with
      granulocytes and mononuclear cells in one CsA-treated pig, while the remaining
      pigs were without histopathological lesions. Pathological changes were noticed in
      one out of five CsA-treated animals, corresponding to the percentage of patients
      treated with CsA who develop CsA encephalopathy. To pursue this finding, two
      studies, one using CsA 20 mg/kg/d for 6 months and one using CsA 10 mg/kg/d for
      12 months, have been initiated.

PMID- 16298582
TI  - Recurrence of hepatitis C after liver transplantation.
AB  - Cirrhosis due to hepatitis C is currently the most common indication for liver
      transplantation in the United States as well as in Europe. The prognosis for
      patients transplanted due to hepatitis C has changed over the years. Today there
      is growing concern as to the prognosis of these patients and how we should treat
      them. This is an overview of the developments in this field concerning treatment
      of recurrence and the role of preemptive treatment.

PMID- 16298583
TI  - Preemptive therapy with pegylated interferon alpha-2b and ribavirin after liver
      transplantation for hepatitis C cirrhosis.
AB  - We present our results of preemptive treatment with pegylated interferon and
      ribavirin after liver transplantation for hepatitis C cirrhosis. PATIENTS:
      Between September 2001 and August 2002, four patients were started on combination
      therapy with pegylated interferon-alpha-2b (1microg/kg weekly) and ribavirin (400
      1000 mg/d) 3 to 4 weeks' posttransplant. Treatment was continued for 6 (genotype
      3a, 2 patients) or 12 (genotype 1b, 2 patients) months. Virologic and biochemical
      responses as well as side effects were evaluated. RESULTS: Two patients (genotype
      3a) became HCV (hepatitis C virus)-RNA negative after 3 months of therapy and are
      persistently negative 20 and 14 months after end of therapy. One patient
      (genotype 1b) became HCV-RNA negative 6 months after start of treatment, but
      therapy had to be withdrawn after 9 months owing to fatigue and suspicion of
      angina pectoris. One patient who was later retransplanted because of hepatic
      artery thrombosis discontinued therapy after 2.5 months owing to anemia,
      leukopenia, and no signs of HCV-RNA reduction. Interestingly, two of the
      responders were nonresponders prior to liver transplant. Median ALT levels at
      start of therapy were 98 U/L (r = 60-126) and 12 months later 40 U/L (r = 24-58)
      (n = 4). No rejection episode was detected. CONCLUSION: In patients liver
      transplanted due to HCV-cirrhosis, combination therapy with pegylated interferon
      and ribavirin can be effective and safe in the early posttransplant period, thus
      preventing recurrent hepatitis C.

PMID- 16298584
TI  - Experience of Mars therapy with and without transplantation in 101 patients with
      liver insufficiency.
AB  - Liver support devices are used to treat life-threatening organ dysfunction until
      a hepatic graft is available or recovery of the native liver. We used a blood
      purification system--molecular adsorbent recycling system (MARS)--that is based
      on removal of both protein-bound and water-soluble substances and toxins. Within
      2.5 years we treated 101 patients, who were stratified to three subgroups: acute
      liver failure (ALF; n = 56), acute decompensation in chronic liver failure
      (AcOCh; n = 35) and liver graft failure (n = 10). MARS seems to be a promising
      therapy for ALF, allowing the patient's own liver to recover or to gain enough
      time to find a liver graft. The most promising results, namely the highest number
      of livers to recovery were observed among acute patients with liver failure due
      to a toxic etiology. However, we did not discover much benefit of MARS for
      patients with AcOCh without liver transplantation.

PMID- 16298585
TI  - Bridge to heart transplantation with the HeartMate device in Gothenburg, Sweden.
AB  - BACKGROUND: Patients rapidly deteriorating while waiting for heart
      transplantation present a major problem. Our strategy for this entity is the
      HeartMate left ventricular assist device (LVAD) VELVAS, an electrically driven
      implantable LVAD. Herein we report our initial experience. METHODS: The medical
      records of all the patients who received HeartMate LVAS at our institution were
      reviewed. RESULTS: From January 1997 through May 2004, 19 patients received a
      HeartMate. The mean age was 39 (15 to 61) years and 84% were men. The diagnoses
      were: dilated cardiomyopathy (n = 8), ischemic heart disease (n = 6), myocarditis
      (n = 3), congenital heart disease (n = 1), and hypertrophic cardiomyopathy (n =
      1). Mean time on LVAD was 113 (10 to 353) days. Ten patients were discharged from
      the hospital to their homes awaiting transplant or recovery. Three patients
      showed recovery of heart function and were subsequently weaned from mechanical
      support. Thirteen patients underwent heart transplantation. Three patients died
      during LVAD treatment. Major adverse events occurred in nine patients, including
      severe right heart failure (n = 3), severe bleeding (n = 3), stroke (n = 1),
      hepatic failure (n = 1), and septicemia (n = 2). Nine of the 13 transplanted
      patients are alive and well today. CONCLUSION: HeartMate LVAS is a valuable
      option for patients rapidly deteriorating while awaiting a heart transplant. Our
      results are comparable with those reported from larger centers.

PMID- 16298586
TI  - Monitoring of the intestinal mucosal perfusion using laser Doppler flowmetry
      after multivisceral transplantation.
AB  - BACKGROUND: Graft endothelium constitutes a prime target during acute rejection.
      Infiltration of T cells, monocytes, and enhanced endothelial-leukocyte
      interactions result in microvascular impairment and altered perfusion. MATERIALS
      AND METHODS: We measured mucosal blood flow using a laser Doppler flowmeter in
      three patients undergoing multivisceral transplantation. Thirty-seven
      measurements were performed through the ileostomy over the first 4 weeks
      posttransplantation. Most measurements were performed within a 24-hour interval
      from endoscopy and biopsy. RESULTS: Mucosal perfusion increased throughout the
      first postoperative week and eventually stabilized around levels specific for
      each patient. Mucosal perfusion remained stable during graft pancreatitis, but
      decreased 35% to 55% from baseline (the average value of the previous
      measurements) during acute rejection and sepsis. During the first week
      posttransplantation there was a gradual increase in mucosal perfusion, which
      might reflect regeneration after reperfusion injury. Increased mucosal perfusion
      did not seem to correlate with rejection or other adverse clinical events. A
      sudden decrease in mucosal perfusion of 30% or more compared to the previous
      measurements was associated with septic episodes and/or rejection.

PMID- 16298587
TI  - Oral feeding with pig peripheral lymphocytes decreases the xenogeneic delayed
      type hypersensitivity reaction in galactosyltransferase knockout mice.
AB  - PURPOSE: Oral tolerance induction has shown promising results in experimental
      allotransplantation models but is not well investigated in xenotransplantation.
      We investigated the possibility to induce tolerance against pig peripheral
      lymphocytes (pPBL) in galactosyltransferase knockout mice (gal -/-), which
      produce antibodies against Galalpha1-3Gal. MATERIAL AND METHODS: Female (gal -/-)
      mice 6 to 8 weeks old weighing 35 to 40 g (n = 10) were fed orally every third
      day five times with 2 x 10(7) isolated, viable pPBL, or with phosphate-buffered
      saline (PBS) only (n = 7). They were then immunized subcutaneously on day 0 with
      a subcellular lysate from 4 x 10(7) isolated, viable pPBL. On day 13, 25 microL
      of a subcellular lysate corresponding to 1 x 10(7) isolated, viable pPBL was
      injected in the right dorsal foot pad, and the delayed type hypersensitivity
      (DTH) reaction was calculated after 24 hours by subtracting the swelling response
      from 25 microL PBS in the left footpad. Anti-Galalpha1-3Gal immunoglobulin IgG
      and IgM antibody titers were measured in the serum before oral feeding and at day
      14. RESULTS: The DTH reaction of the pPBL fed mice was 0.07 +/- 0.05 mm vs 0.57
      +/- 0.23 mm for the controls (P < .001). No significant differences in anti Gal
      alpha1-3 Gal IgG and IgM antibody titers were seen. CONCLUSIONS: This study
      demonstrates for the first time that oral delivery of pPBL can counteract the
      indirect T-cell reaction against xenogeneic subcellular antigens from pPBL. These
      observations warrant further investigation in immunologically modified mice and
      perhaps in primate models of xenotransplantation.

PMID- 16298588
TI  - Ischemic preconditioning can overcome the effect of moderate to severe cold
      ischemia on concordant mouse xeno-heart transplants.
AB  - PURPOSE: Concordant mouse xeno-heart transplants are relatively sensitive to
      ischemia-reperfusion injury. We investigated the effect of an ischemic
      preconditioning (IPC) protocol on the functional and biochemical outcome of mouse
      xenohearts transplanted to the Lewis rat. MATERIAL AND METHODS: NMRI mice (30 to
      40 g) were anesthetized, intubated, and mechanically ventilated. They were
      subjected either to a IPC protocol leading to an SaO(2) of 70% for 5 minutes
      followed by normoxia (defined as SaO(2) >90%) for 10 minutes (n = 9) or normoxia
      only (n = 11). The hearts were then heterotopically transplanted to Lewis rats
      (220 g). The frequencies of immediate onset and early dysfunction and late
      dysfunction were registered. The hearts surviving for 6 hours were explanted and
      the absolute concentrations of phosphocreatine and adenosine triphosphate (ATP)
      were determined in micromole per gram of heart tissue with high-pressure liquid
      chromatography. The phosphorylation ratio, PCr/ATP, a known correlate to
      biochemical and functional outcome, was calculated. RESULTS: Four of 11 (36.4%)
      of control hearts experienced immediate onset and early dysfunction versus 0%
      (0/9) in M hearts subjected to IPC (P = .01). Furthermore, the IPC protocol
      increased the PCr concentration, 15.08 +/- 1.00 versus 9.04 +/- 2.04 micromol/g
      in controls (P = .01), and the PCr/ATP ratio, 1.80 +/- 0.17 versus 1.27 +/- 0.21
      (NS; P = .06). CONCLUSIONS: IPC provides a protective PCr overshoot overcoming
      the short-term effects of moderate to severe ischemic injury on mouse xeno-heart
      transplants.

PMID- 16298589
TI  - Antibodies to liver sinusoidal endothelial cells modulate immune responses in
      liver transplantation.
AB  - AIM: Liver sinusoidal endothelial cells (LSECs) have been implicated to play a
      role in the induction of liver allograft rejections. Here, we studied the
      clinical consequences of preformed LSEC-reactive antibodies and their functional
      capacity in modulating T-cell responses. METHODS: Pre- and posttransplant sera
      and T lymphocytes from 95 liver transplant patients were used in this study.
      LSECs were isolated from a normal healthy liver. Binding of antibodies to LSECs
      was detected using flow cytometric analysis. To study whether LSEC antibodies
      facilitated cell-mediated immunity, a mixed cell culture (MCC) assay was used.
      Cytokines in the supernatant of MCC were also measured by enzyme-linked
      immunosorbent assay. Immunohistochemical staining on liver biopsy sections was
      performed to detect deposition of immunoglobulins in LSEC during rejections.
      RESULTS: Significantly higher numbers of patients with rejections had LSEC
      antibodies (35/50, 70%) compared with 8/45 (18%) without rejections (P < .0001).
      Purified fractions of LSEC antibodies induced the expression of the costimulatory
      marker CD86 on LSECs. Significantly higher numbers of patients with LSEC
      antibodies and rejections had an increased proliferation of T cells and markedly
      decreased levels of transforming growth factor (TGF)-beta in the MCC as compared
      with those without antibodies and rejections (P < .0001, P < .0001,
      respectively). Deposition of antibodies in LSECs during rejection episodes was
      observed in the biopsies of patients with LSEC antibodies but not in those
      without LSEC antibodies. CONCLUSION: Our data suggest that antibodies to LSEC may
      facilitate acute liver allograft rejections by down-regulating the immune
      modulating cytokine TGF-beta and thus up-regulating alloreactive T-cell
      proliferation.

PMID- 16298590
TI  - Nitric oxide-mediated effects on liver blood flow.
AB  - We investigated whether blockade of nitric oxide synthase by the arginine analog
      l- NAME could affect peripheral liver blood flow (PLBF) or hepatocyte integrity
      (serum ALT) in either a control series or in a series subjected to mild reduction
      of liver blood flow by temporary clamping of the hepatic artery (HA).
      Anesthetized rats were arranged for mean arterial pressure (MAP) recordings via a
      carotid artery, drug injections, and blood sampling via a jugular vein, and
      monitoring of PLBF using a laser Doppler flowmeter. In series 1, the rats
      received either l-NAME (30 mg/kg i.v.) or NaCl. l-NAME caused a significant
      decrease in PLBF and an increase in MAP compared to NaCl; ALT did not differ. In
      series 2, l-NAME (30 mg/kg i.v.) or NaCl was administered at the beginning of the
      experiment. After 60 minutes of equilibration, the HA was clamped for 60 minutes
      then unclamped for another 60 minutes. As in series 1, the l-NAME group had
      significantly lower PLBF and higher MAP than the NaCl group. Occlusion of the HA
      resulted in significantly greater reduction in PLBF in the NaCl versus the l-NAME
      group. Upon unclamping, there was no difference in ALT levels, PLBF, or MAP. To
      conclude, NO displayed a positive tonic effect on liver blood flow, reduction of
      which with l-NAME did not aggravate mild ischemia/reperfusion injury in this
      model.

PMID- 16298592
TI  - Laparoscopic nephrectomy: safe and comfortable surgical alternative for living
      donors and for good results of graft function.
AB  - Laparoscopic nephrectomy for kidney donation from living related donors has the
      advantages of a less invasive surgical access, better cosmesis, and a shorter
      hospital stay for the donor. However, some workers have reported up to 10% life
      threatening complications for the donor using this technique. The purpose of our
      study was to evaluate hand-assisted laparoscopic nephrectomy for living donors of
      kidney transplants in terms of graft function. Thirty donors who underwent open
      nephrectomy (ON) were compared with 27 who had hand-assisted nephrectomy (HALN).
      Surgery and ischemia times, hospital stay, bleeding, graft function, remaining
      kidney function, and complications were compared in both groups. Mean surgery
      time was 126.9 minutes for ON and 98 minutes for HALN (P = .0005), warm ischemia
      time was 3 minutes versus 6 for ON vs HALN, respectively (P = .02).
      Hospitalization stay was 6.3 days for ON versus 4.8 days for HALN (P = .0015).
      Differences in change in hematocrit and in serum creatinine levels were not
      significant; graft outcomes were also similar. Complications were minimal. We
      conclude that HALN is a valid, safe technique to obtain kidneys from living
      related donors, significantly reducing the hospital stay and allowing return to
      normal activities sooner, with risks falling within those reported in the
      literature.

PMID- 16298593
TI  - Influence of the kidney histology at the time of donation on long term kidney
      function in living kidney donors.
AB  - Living donation is the best choice for kidney transplantation, obtaining long
      lasting good results for the recipient. Some concern still remains regarding the
      donor's long-term health. Kidney biopsy was routinely performed in our donor
      population at the time of donation many years ago. We found the existence of
      morphological kidney disease in those samples, in spite of normal clinical
      evaluations before donation. We attempted to correlate those abnormalities with
      long-term clinical outcomes. Donors were at least 10 years after surgery. A
      medical interview, including the SF-36 Health Survey, laboratory evaluation, and
      ambulatory blood pressure monitoring was performed on 27 donors meeting the
      inclusion criteria. Two donors had died after donation from unrelated causes with
      no known nephropathy. Histological analysis showed abnormalities in 16 of 29
      donors. We found an increased prevalence of hypertension compared to the general
      population. Interestingly, there was no proteinuria in the donor population, and
      none developed clinical nephropathy. All subjects felt emotionally rewarded with
      donation, stating that their lives had no limitations. Our results suggest that
      kidney biopsy is neither necessary nor useful prior to donation because, although
      many donors had morphological kidney disease, none developed clinical nephropathy
      in the long term.

PMID- 16298594
TI  - Comparison of cyclosporine concentrations 2 hours post-dose determined using 3
      different methods and trough level in pediatric renal transplantation.
AB  - Immunosuppression has been one of the great challenges in pediatric recipients of
      kidney allografts. Cyclosporine (CsA) has evolved during the past 25 years of
      transplantation. It requires frequent blood level monitoring because of its
      narrow therapeutic window and interpatient and intrapatient variability. Neoral
      (Novartis) is no exception. Ideally, monitoring of blood levels should also
      include determination of the area under the time-concentration curve (AUC) to
      better target the therapeutic window, thus avoiding underdosing or overdosing,
      especially in pediatric patients. A single blood concentration measurement 2
      hours after Neoral administration (C2) has been shown to be a more for accurate
      predictor of drug exposure than trough levels (C0). Therefore, its use may lead
      to reduction in the incidence and severity of cellular rejection and of CsA
      toxicity. Some studies have shown that the metabolites/CsA ratio is substantially
      lower using C2 than C0, however, the between-assay differences for C2 monitoring
      have not been considered. The purpose of this study was to evaluate CsA C0 and C2
      levels, determined using monoclonal fluorescence polarization immunoassay
      (FPIA)/TDx and enzyme multiplied immunoassay (EMIT). CsA levels were determined
      using a radioimmunoassay (RIA) in 30 pediatric transplant recipients with stable
      renal function within 42.7 mean months follow-up. Mean age was 13.4 years; 15
      children were girls; 23 patients were recipients of cadaveric kidneys. The mean
      CsA microemulsion dose was 5.7 mg/kg/d. The 3 methods showed a high correlation
      between C0 and C2 (r > or = 0.97). A linear regression slope was significantly
      higher for C0 than C2 (P < .001). The CsA concentrations both at C0 and C2 were
      significantly higher with FPIA than with RIA (P < .009) but no differences were
      found for EMITT (P = .2). The mean C0 level for FPIA was 22% and 26% higher than
      RIA and EMIT, respectively. The mean C2, for FPIA was 7% and 12% higher than RIA
      and EMIT, respectively. In conclusion, CsA levels determined using RIA or EMIT
      are better than using FPIA/Tx; also, C2 CsA levels are more accurate than C0 in
      pediatric transplantation patients.

PMID- 16298595
TI  - Importance of early adequate exposure to cyclosporine in renal transplant
      outcome: study of 1-year creatinine.
AB  - INTRODUCTION: One-year serum creatinine (SCr) level has been used as a surrogate
      marker for graft survival in kidney transplantation. We evaluated the importance
      of different factors on this parameter, emphasizing the importance of adequate
      exposure to Cyclosporine (CyA). METHODS: Ninety-six consecutive renal transplant
      recipients who underwent transplantation between 1996 and 2002 were treated with
      CyA, steroids, and azathioprine. Univariate and multivariate regression analyses
      were performed for 1-year SCr, acute rejection episodes (ARE), and duration of
      delayed graft function (DGF). We considered adequate CyA levels within 1 week to
      be >250 ng/mL trough levels (38%) or 3 hour postdose level (C3) >1100 ng/mL
      (62%). RESULTS: Mean 1-year SCr was 1.52 +/- 0.5, ARE rate was 27%, and DGF rate
      was 31%. Overall, 53% of patients achieved adequate exposure to CyA at 1 week
      (68% on those monitored by C3). Univariate analysis identified female recipient
      gender, decreasing donor age, absence of ARE, and decreased DGF duration to yield
      lower 1-year SCr (P < .05). On multivariate analysis for donor age (lower), ARE
      rate, and duration of DGF (shorter) were the only factors considered to be
      significant for a lower 1-year SCr level. Multivariate analysis for ARE showed
      that adequate CyA exposure and lower HLA mismatch decreased ARE, whereas the
      ability to achieve adequate exposure to CyA and shorter cold ischemia time (CIT)
      correlated with a reduced incidence of DGF. CONCLUSIONS: One-year SCr level is
      affected primarily by the incidence of ARE, by donor age, and by duration of DGF.
      Adequate CyA exposure is related to lower ARE; however, its relation to DGF may
      be influenced by the reluctance to increase exposure on patients with a
      nonfunctioning graft.

PMID- 16298596
TI  - Benefits of early biopsy on the outcome of kidney transplantation.
AB  - INTRODUCTION: Delayed graft function has been associated with worse long-term
      kidney allograft survival. Adequate diagnosis of the etiology of dysfunction is
      crucial, often requiring routine early biopsies. The aim of this article was to
      report the results and safety of early kidney allograft biopsies and how they
      influenced its management. METHOD: Between September 1994 and July 2004, 134
      renal transplant recipients were prescribed cyclosporine (CsA; Neoral, Novartis,
      Chile), steroids, and a third agent (azathioprine in 92% of the graft
      recipients). Thirty-four patients (26%) had a kidney biopsy performed within the
      first week because of allograft dysfunction. RESULTS: The main diagnosis was
      acute tubular necrosis (ATN) in 22 patients (65%), whereas 6 (18%) were diagnosed
      with an acute rejection episode (ARE), allowing prompt initiation of therapy with
      reversal of rejection in 4 of them. Two patients (6%) showed signs of thrombotic
      microangiopathy (TMA) induced by CsA, which subsided following a switch from CsA
      to tacrolimus (Prograf Pharmainvesti, Chile). In 2 patients, the biopsy specimen
      showed signs of CsA nephrotoxicity that reverted following dose reduction.
      Finally, in 2 patients, the biopsy specimen showed chronic nephropathy of donor
      origin, which had not been previously recognized, resulting in graft loss. There
      was only one major complication related to the biopsy, intraperitoneal bleeding
      that required surgical treatment. CONCLUSIONS: Early allograft biopsy is safe
      and, in a significant number of cases (30%), it detects important allograft
      pathology (ARE, TMA, and drug toxicity), which when adequately and promptly
      treated may rescue the graft.

PMID- 16298597
TI  - No gender-associated differences of cyclosporine pharmacokinetics in stable renal
      transplant patients treated with diltiazem.
AB  - Cytochrome-P450 enzymes metabolize cyclosporine both in the liver and in the
      intestinal wall. Diltiazem, by competitive inhibition of these enzymes, may
      increase the absorption and the bioavailability of cyclosporine. Some evidence
      points to a higher activity of some specific enzymes in women, such as CYP3A,
      that may influence differences in cyclosporine pharmacokinetics. We examined
      possible gender-associated differences in pharmacokinetic profiles of
      cyclosporine in 19 stable renal transplant recipients cotreated with diltiazem.
      Ten women and nine men, chronically using diltiazem associated with cyclosporine,
      azathioprine, and prednisone were randomly assigned to an 8-week period of
      continued controlled treatment with diltiazem (10 patients) or a wash-out period
      discontinuing diltiazem (nine patients). At the end of this period, the time
      concentration curves of cyclosporine in the first 4 hours were performed after a
      single dose of cyclosporine. Thereafter, a cross-over between groups was
      performed, and time-concentration curves repeated. A specific RIA was used to
      measure cyclosporine concentrations. Comparisons between male and female patients
      in doses of cyclosporine and other pharmacokinetics parameters (C(0), C(2), AUC(0
      4)), with or without diltiazem, did not show any difference related to gender.
      The association of diltiazem allowed a similar degree of reduction in Neoral
      dosage in male and female patients (21%). No changes in serum creatinine, blood
      urea nitrogen, potassium, uric acid, or blood pressure, or other adverse event
      were observed during the study. In these groups of patients, gender was not an
      important factor to be considered when diltiazem is added to cyclosporine
      therapy.

PMID- 16298598
TI  - Human leukocyte antigens in indigenous (mapuche) people in a regional renal
      transplantation program in chile.
AB  - An active regional transplantation program established in the southern region of
      Chile has allowed the incorporation of ethnic minorities particularly Mapuche
      living in this geographic area in the development of a histocompatibility
      database. To identify possible differences in the human leukocyte (HLA) antigen
      distribution in Chilean Mapuche compared with non-Mapuche, we reviewed 442 HLA
      tissue-typing studies. Seventy-eight of 309 recipients (25%) and 18 of 133 donors
      (13%) were Mapuche. Among recipients, Mapuche people showed a significantly
      higher frequency of the HLA antigens, A28, B16, DR4, and DR8, and a lower one for
      A19, B15, and DR1 (P < .05) compared with non-Mapuche individuals. A particularly
      higher frequency of the haplotype A28, -B16, -DR4 was also evidenced in Mapuche.
      Besides, these recipients showed a higher frequency of the allele -DR4 when
      compared with Mapuche donors. A greater frequency of some histocompatibility
      antigens in patients with chronic renal disease might be attributed to allelic
      concentration due to a high index of endogamy, but a possible association with
      the development of progressive renal disease cannot be ignored, especially when a
      higher prevalence of DR4 was observed among Mapuche recipients.

PMID- 16298599
TI  - Pediatric liver transplantation: ten years of experience in a multicentric
      program in Chile.
AB  - Liver transplantation is the only treatment for patients with terminal acute and
      chronic diseases. Liver transplantation was started in Chile in 1985; our
      pediatric program began in 1993. The aim of this paper work was to present our
      experience from 1993 through 2004. One hundred and thirty two orthotopic liver
      transplants (OLT) were performed in children of mean age 5 years and median age 4
      years (8 months to 15 years). The most frequent indications were biliary atresia,
      (43.1%) and acute liver failure (ALF; 20.4%), whose frequent cause was unknown
      but viral hepatitis A was the second one. A complete liver was transplanted in 59
      patients, reduced in 39, split in one, and as an auxiliary liver in another one.
      Living related liver transplantation was performed in 32 cases (24.2%), of which
      thirty included segments II and III, and two, a right liver. A terminal arterial
      anastomosis was performed in 102 (77.2%) recipients and a graft interposition in
      32 patients (24.2%). In 16 cases, biliary reconstruction was performed through an
      enterobiliary anastomosis. Immunosuppression included cyclosporine (Neoral),
      steroids, and azathioprine with conversion to tacrolimus (Prograf) as indicated.
      Rejection episodes, which were always biopsy-proven, were treated either with
      methylprednisolone or with antibodies. Biliary complications were the most
      frequent (21.4%) and the second cause was vascular complications (13%). Sixty-six
      patients suffered an acute rejection episode. Actuarial graft survival was 81.3%
      at 1 year and 72% at 5 years, while actuarial graft survival for ALF was 75.9% at
      1 year and 67.8% at 5 years. Our results are comparable to those reported by most
      international groups.

PMID- 16298601
TI  - Combined liver and kidney transplantation in a multicenter transplantation
      program in Chile.
AB  - INTRODUCTION: Combined liver and kidney transplantation (CLKT) is an exceptional
      therapeutic procedure limited to a few diseases with advanced compromise of these
      organs. Hyperoxaluria type I and polycystic disease are the most frequent
      indications. The aim of this article was to report our indications and results of
      CLKT in a multicenter transplantation program in Chile. MATERIAL AND METHODS: Our
      Excel database was reviewed to select patients who were treated with CLKT between
      1993 and July 2004. RESULTS: Among 242 liver transplantations (LT) and 48 kidney
      transplantations (KT), 7 were CLKT, representing 2.8% of LT and 14.5% of KT. Four
      patients were women and 3 were male of average age 46.8 years. One patient was a
      child. Most frequent indications were chronic renal failure associated with
      terminal liver disease and polycystic disease. One patient needed liver
      retransplantation due to hepatic vein thrombosis. One patient had a biliary
      fistula and another had a urinary fistula, treated conservatively. Acute liver
      rejection took place in 3 cases, 1 of which required antibodies. Two patients
      died, 1 due to aspergillosis and the other due to vascular complications in the
      transplanted liver. Actuarial survival rates were 71.4% at 1 and 5 years. Chronic
      renal failure is not a contraindication to LT. CONCLUSION: CLKT is an acceptable
      option for these patients.

PMID- 16298600
TI  - Living related liver transplantation. Why this option has been discarded in a
      pediatric liver transplant program in Chile.
AB  - Living related living transplantation (LRLT) has opened new possibilities for
      planning transplantation in better conditions for children with emergency
      situations and chronic liver diseases. Since we began the LRLT program in 1999,
      we have performed 57 pediatric liver transplants, 17 (29.8%) using living related
      donors (LRD). The aim of this study was to analyze the reasons why LRD were
      discarded as a therapeutic option. All pediatric patients were prospectively
      included in our Microsoft Excel database that was reviewed for obtaining
      information about causes why the LRLT could not be done. LRLT was proposed in 28
      cases and performed in 17 (60.7%). The reasons for LRD rejection were: parent's
      fear of surgical complications in four cases; drug abuse in two; a mother without
      family support; medical reasons in two; and only one, due to anatomical reasons
      and in one case, cadaveric graft transplantation was performed while completing
      the father's evaluation. From these eleven cases, the indications for liver
      transplant were acute liver failure (ALF) in seven, biliary atresia in three, and
      Alagille syndrome in one. Nine were transplanted with cadaveric organs, but two
      patients with ALF died awaiting a liver. Efforts should be made to clarify the
      advantages and the disadvantages of LRD in each case, allowing parents to make a
      free, well-informed decision.

PMID- 16298603
TI  - Kyoto islet isolation method: the optimized one for non-heart-beating donors with
      highly efficient islet retrieval.
AB  - The availability of pancreata for clinical cadaveric islet transplantation is
      restricted to non-heart-beating donors (NHBDs) in Japan. This forced us to modify
      the current standard islet isolation protocol that was made up for brain-dead
      donors and make it suitable for NHBDs. The Kyoto islet isolation method is the
      one with induction of several steps based on the ideas both already reported
      literally and invented originally by ourselves. Using this islet isolation
      method, we isolated islets from 13 human pancreata of NHBDs and transplanted 11
      preparations to six type-1 diabetic patients. The rate to meet release criteria
      of Edmonton protocol was 84.6%. Establishment of this method allowed us to begin
      a clinical islet transplantation program in Japan and to continue to perform the
      preparation of islets from NHBDs with high rate to meet the release criteria of
      the Edmonton protocol.

PMID- 16298604
TI  - In situ cooling of pancreata from non-heart-beating donors prior to procurement
      for islet transplantation.
AB  - BACKGROUND: The specific aim of this study was to develop an effective technique
      for pancreas procurement for islet transplantation from a non-heart-beating donor
      (NHBD). METHODS: Between January 2004 and November 2004, 11 human pancreata were
      procured and processed for islet isolation at a cell processing center. After
      confirmation of brain-death status, a double-balloon catheter was inserted to
      prevent warm ischemic damage to the donor pancreas by using an in situ regional
      organ cooling system that was originally developed for kidney procurement.
      RESULTS: Warm ischemic time was controlled with the modified in situ regional
      cooling system at 6.0 +/- 0.9 minutes (mean +/- SE). The operations for
      procurement of the kidneys and pancreata lasted 48.1 +/- 3.6 minutes and 9.9 +/-
      4.8 minutes, respectively. The islet yield per isolation was 396,767 +/- 142,842
      IE (islet equivalents). Ten of the 11 cases met the criteria for pancreatic islet
      transplantation based on the Edmonton protocol. CONCLUSIONS: We developed a novel
      procurement technique in cooperation with our kidney procurement team. This
      protocol for the procurement of pancreas and kidney from an NHBD enabled us to
      transplant islets into a type 1 diabetic patient and kidney into a renal failure
      patient.

PMID- 16298605
TI  - A comparison of cold storage solutions for pancreas preservation prior to islet
      isolation.
AB  - BACKGROUND: Several solutions are used to preserve the pancreas prior to islet
      isolation. This study sought to assess whether the type of solution had an impact
      on the isolation outcome. METHODS: We reviewed data from 125 islet isolation
      procedures performed from January 2002 to January 2005. Pancreata were preserved
      in University of Wisconsin (UW) (n = 101), Celsior (CS) (n = 19), or IGL-1 (n =
      5) solutions. Islet isolation results and transplantation rates were compared
      between groups. RESULTS: UW, CS, and IGL-1 groups were similar according to
      donor's age, weight, and body mass index. Weight of undigested pancreas was 20 +/
      13.1, 21.4 +/- 15.7, and 17.4 +/- 8.7 g for UW, CS, and IGL-1, respectively (P >
      .2). Final total number of IEQ was 267,000 +/- 132,000, 277,000 +/- 155,000, and
      311,000 +/- 163,000, respectively (P > .4). Success rate (defined as >250,000
      IEQ) was 55.5%, 52.9%, and 60% for UW, Celsior, and IGL-1 (P > .9); the
      transplantation rate was 42.2% for UW, 36.8% for Celsior, and 80% for IGL-1
      preservation (P > .2). CONCLUSIONS: In this preliminary study, UW, Celsior, and
      IGL-1 solutions demonstrated similar islet isolation results. The new IGL-1
      solution appears promising.

PMID- 16298606
TI  - Two-layer method in short-term pancreas preservation for successful islet
      isolation.
AB  - BACKGROUND: We sought to determine whether the two-layer method (TLM) offers
      advantages over UW storage solution for locally procured pancreata with cold
      ischemia time of <8 hours for successful islet isolation. METHODS: From October
      2003 through February 2005, 22 human pancreata were procured locally from
      cadaveric donors and preserved using UW solution (n = 11) or TLM (n = 11).
      RESULTS: Donor characteristics were similar in the two groups, with no
      statistical difference. Cold ischemia time was 4.5 +/- 0.6 (2.5 to 8) hours in
      the UW and 5.1 +/- 0.5 (3 to 8) hours in TLM group (P > .05). Organs preserved
      with TLM were exposed to PFC for 4 +/- 0.5 (2 to 7.5) hours. After TLM
      preservation, 8 of 11 (72%) pancreata yielded >300,000 IEQ pancreatic islets,
      which met all criteria for clinical transplantation; after UW cold storage, only
      3 of 11 isolations were equally successful (27%) (P < .05). Mean IEQ was higher
      in the TLM than in the UW group: 349,000 +/- 37,000 vs 277,800 +/- 34,000; IEQ/g
      was also higher at 5100 +/- 760 vs 3000 +/- 570, respectively (P < .05). Islet
      quality, characterized by purity, viability, and insulin SI, did not differ
      statistically in the two groups: 67 +/- 4 vs 74 +/- 4%, 87 +/- 2 vs 83 +/- 4%,
      and 4 +/- 0.7 vs 4.8 +/- 1, respectively (P > .05). CONCLUSIONS: The Two Layer
      Method for locally procured human pancreata with cold ischemia time lower than 8
      hours offers significant advantage over UW cold storage increasing the pancreatic
      islet isolation yield and the isolation success rate.

PMID- 16298607
TI  - Analysis on donor and isolation-related factors of successful isolation of human
      islet of Langerhans from human cadaveric donors.
AB  - We analyzed the preexisting donor factors and isolation variables that affected
      isolation of human islets of Langerhans. Sixty-nine pancreata from cadaveric
      donors were analyzed for donor factors of age, gender, body mass index, cause of
      death as well as graft factors of cold ischemia time, pancreas status,
      distensibility during intraductal collagenase distension and time of collagenase
      expansion and digestion. Islet isolations that recovered >100,000 IEQ (n = 53)
      were compared to those generating less than 100,000 IEQ (n = 16) to analyze the
      factors affecting islet yield during donor harvest and isolation procedures. The
      mean islet recovery was 216.0 x 10(3) (IEQ) or 2840 (IEQ) per gram of pancreas.
      Mean purity was 54%. The success rate of islet isolation was 76%. Mean age was 31
      years, and mean cold ischemia time was 6.9 hours. In univariate analysis, the
      status of the pancreas was the only significant factor for successful isolation,
      and gender, time of collagenase expansion and digestion were marginal factors. In
      stepwise multivariate logistic regression analysis of donor and isolation-related
      factors, donor gender, pancreas status and digestion time were significant
      factors. During the same period we performed three cases of clinical islet
      allotransplantation and one autotransplantation. This study confirmed that the
      same donor factors and variables in the isolation process can affect the ability
      to obtain successful human islet isolation. Enough experience and pertinent
      review of donor and isolation factors can make islet isolation consistent,
      supporting clinical islet transplantation without unnecessary cost.

PMID- 16298608
TI  - Internal assessment of a novel islet isolation facility in Spain.
AB  - Islet transplantation is a promising therapy in the treatment of diabetes
      mellitus. Herein we present the result from the first series of islet isolations
      carried out in our new islet isolation facility. The aims of study were to
      analyze the influence of various donor characteristics on the success of islet
      isolation and compare these outcomes with other European and American groups.
      Data from 22 completed islet isolation were used to compare donor and isolation
      variables among successful (>300,000 IEQs) versus unsuccessful isolations. The
      successful isolation rate from our laboratory was 31.8%. We did not see any
      significant differences between successful and unsuccessful groups according to
      donor characteristics, although age was close to significance (38.57 +/- 10.29
      versus 48.33 +/- 12.39; P = .08). Donor age (1.12 [1.23; 0.99]) and body mass
      index (0.065 [1.32; 3.08]) were associated with isolation success in a logistic
      regression model. We did not find differences among intraprocedure variables with
      the exception of IEQ prepurification (409,073 +/- 115,041 versus 263,776 +/-
      128,988; P < .05). IEQpre and IEQpost were positively correlated (P < .05). In
      comparison with other groups, we observed differences in some cases related to
      islet yield prepurification (P < .05) but not postpurification. Purity from our
      islet preparations was the highest from all considered groups (P < .05). Recovery
      was similar in all groups. CONCLUSIONS: In our experience, donor characteristics
      have no influence on the success rate. The digestion step is a critical factor
      for success. Our results with respect to IE yield were close to that of
      experienced groups.

PMID- 16298609
TI  - Islet isolation and GMP, ISO 9001:2000: what do we need--a 3-year experience.
AB  - Pancreatic islet cell isolation and transplantation has been performed for many
      years at several institutions. Although all institutions aim to produce high
      quality islets, applied standards widely deviate from standards in the
      pharmaceutical industry. The legal situation within the European Union has
      changed requirements for setting up and running such a laboratory. The process is
      now clearly defined as a production of a pharmaceutical and therefore must be
      licensed by federal authorities. Analysis of workload for establishing an islet
      isolation program that fulfil GMP and ISO 9001 criteria including an estimation
      of costs and the impact of such a system on the isolation process. The definition
      of quality parameters and documentation is a central issue of all islet isolation
      laboratories. Therefore, GMP and ISO 9001:2000 do not add additional work per se.
      On the other hand, clear guidelines, a clear policy, working place descriptions,
      forms, checklists, and, particularly standard operating procedures, are
      instrumental for smooth functioning within the department. Collection of data
      such as errors, improvement measures, and preventive measures reduces subsequent
      costs. A clear definition of responsibilities minimizes organizational problems.
      Steering of inspection devices prevents bias errors and validating the processes
      clearly points out incorrect assumptions. Documentation helps to prove the
      correctness of the production at any time and is of use also for scientific
      evaluations. We strongly feel that GMP criteria are mandatory and together with
      an ISO 9001:2000 quality management system offers significant advantages for the
      process of islet isolation and a continuous improvement process.

PMID- 16298610
TI  - "Real-time" assessment of human islet preparations with confocal live cell
      imaging.
AB  - Pancreatic islet cell transplantation is a promising approach to restoring
      normoglycemia in diabetic patients. The outcome of islet transplantation is
      uncertain for two reasons: The quality of isolated islets is still poorly defined
      and the functional potential of transplanted islets is difficult to predict.
      Therefore, one of the primary challenges in islet transplantation is to identify
      and understand the changes taking place in islets after isolation and culture.
      Description of such changes in living islet cells offers insights not achievable
      by use of fixed-cell techniques. Three fluorescent dyes,
      dichlorodihydrofluorescein diacetate, tetramethylrhodamine methyl ester
      perchlorate (TMRM), and fluorescent wheat germ agglutinin, were used to assess
      either overall oxidative stress, time-dependent mitochondrial membrane
      potentials, or localization of oligosaccharides. Confocal microscopy was
      performed with a microlens-enhanced Nipkow disk-based confocal system mounted on
      an inverse microscope. We were able to show differences in the amount of
      oligosaccharides on the cell surface between endocrine and exocrine cells in
      freshly isolated human islet preparations. The study of the mitochondrial
      membrane potential via TMRM proved to be useful to early identification of
      damaged or stressed cells. Thus a combination of fluorescent dyes as subcellular
      markers, with a powerful live confocal imaging system may be of great value to
      isolation and culture.

PMID- 16298611
TI  - High-density culture of human islets on top of silicone rubber membranes.
AB  - Islet culture has emerged as a standard practice prior to clinical
      transplantation. However, culturing large numbers of islets requires low islet
      density (number of islets per unit surface area) and, consequently, 20 to 30
      flasks per pancreas in order to avoid hypoxia-induced death (HID). There is a
      need for a simple, practical, small-footprint culture vessel that will
      accommodate aseptic maintenance of entire human islet isolations while avoiding
      HID. In this communication, we examine the hypothesis that by improving oxygen
      transfer through culture of islets on silicone rubber membranes (SRM), we may
      increase islet surface coverage and reduce the number of flasks required while
      avoiding HID. Our results demonstrate that islets cultured for up to 48 hours in
      vessels with SRM bottoms at 2000 to 4000 islet equivalents (IE)/cm(2), a surface
      coverage 10- to 20-fold higher than the standard culture protocol, displayed no
      significant loss of viability. In contrast, islets cultured for 48 hours at 4000
      IE/cm(2) in flasks with gas-impermeable bottoms suffered a 60% to 70% reduction
      in viability. The data suggest that it is possible to culture all islets isolated
      from a human pancreas on SRM in a single, standard-sized vessel while maintaining
      the same viability as with the current, standard culture protocols that require
      20 to 30 flasks. This approach may lead to substantial improvements in islet
      culture for research and clinical transplantation.

PMID- 16298612
TI  - Assessment of human islet viability using various mouse models.
AB  - To date no in vitro viability test is known to accurately predict in vivo human
      islet function, making transplantation into various nonimmune animal models
      mandatory. The diabetic mouse model has been proposed as a standard method for
      human islet viability assessment. However, the use of streptozotocin for diabetes
      induction is associated with inconsistency with respect to induction protocols
      and the significant mortality rate. The purpose of this study was to compare a
      nondiabetic NOD-scid mouse model to its diabetic counterpart in terms of
      predicting islet viability. Diabetes was induced in NOD-scid mice using
      intraperitoneal injection of streptozotocin at concentrations ranging from 100 to
      200 mg/kg. Blood glucose levels were monitored for 7 to 10 days, and mice that
      had levels of >300 mg/dL were used in the experiment. For nondiabetic mice, blood
      glucose and baseline human C-peptide levels were checked after an overnight fast.
      Transplantation of 2000 human islet equivalent was done in both models using the
      same technique. Islet function was determined in the diabetic mice by return to
      normoglycemia for 2 consecutive days and measurement of fasting human C-peptide
      on days 7 and 14 posttransplant. Viability was tested in nondiabetic mice after
      intraperitoneal injection of glucose (2 g/kg) and the measurement of human C
      peptide levels using radioimmunoassay. Titration of the streptozotocin dose from
      200 to 100 mg/kg showed a significant reduction in mice mortality (40% to 10%)
      and an increase of diabetes induction (55% to 81%). The 23 human islet isolations
      tested in both models showed complete consistency of the viability results.

PMID- 16298613
TI  - Multi-lot analysis of custom collagenase enzyme blend in human islet isolations.
AB  - INTRODUCTION: Variability currently in Liberase HI from lot to lot limits the
      ability to effectively isolate islets with consistency. Roche Diagnostics Inc
      (Indianapolis, Ind, USA) has developed a Custom Collagenase enzyme blend in hopes
      that producing collagenase II and I and thermolysin separately will eliminate
      variability. In this study we examined the variability in Custom Collagenase lots
      in respect to isolation results and isolation success rates and compared those to
      Liberase HI. METHODS: We retrospectively analyzed records from 68 islet
      isolations where either Liberase HI (lot A: n = 23, Lot B: n = 20) or Custom
      Collagenase blend (Lot C: n = 10, Lot D: n = 15) was employed. Human islets were
      isolated from cadaveric pancreata using standardized methods performed in a
      controlled islet isolation facility. RESULTS: Analysis of Liberase HI and Custom
      Collagenase using Student t test showed no difference between the two groups.
      Comparison of the two Custom Collagenase lots using the t test showed a
      statistical difference between undigested pancreas weight and pancreas digestion
      times. Using chi-square test, no statistical significance was found in isolation
      success rates from lot to lot. CONCLUSION: Although the Custom Collagenase blend
      is comparable to Liberase HI in its ability to isolate human islets, variability
      still exists from lot to lot when used conventionally as Liberase HI is. The
      ability to predetermine doses is beneficial, and as techniques to manipulate the
      activity levels prior to isolations improve so to will the enzymes' ability to
      isolate islets on a consistent basis.

PMID- 16298614
TI  - Multipotent progenitor cells isolated from adult human pancreatic tissue.
AB  - The supply of islet cells is a limiting factor for the widespread application of
      islet transplantation of type-1 diabetes. Islets constitute 1% to 2% of
      pancreatic tissue, leaving approximately 98% as discard after islet isolation and
      purification. In this report we present our data on the isolation of multipotent
      progenitor cells from discarded adult human pancreatic tissue. The collected
      cells from discarded nonislet fractions, after enzymatic digestion and gradient
      purification of islets, were dissociated for suspension culture in a serum-free
      medium. The cell clusters grown to a size of 100 to 150 mum contained cells
      staining for stage-specific embryonic antigens, but not insulin or C-peptide. To
      direct cell differentiation toward islets, clusters were recultured in a
      pancreatic differentiation medium. Insulin and C-peptide-positive cells by
      immunocytochemistry appeared within a week, reaching over 10% of the cell
      population. Glucagon and somatostatin-positive cells were also detected. The cell
      clusters were found to secrete insulin in response to glucose stimulation. Cells
      from the same clusters also had the capacity for differentiation into neural
      cells, as documented by staining for neural and glial cell markers when cultured
      as monolayers in media containing neurotrophic factors. These data suggest that
      multipotent pancreatic progenitor cells exist within the human pancreatic tissue
      that is typically discarded during islet isolation procedures. These adult
      progenitor cells can be successfully differentiated into insulin-producing cells,
      and thus they have the potential for treatment of type-1 diabetes mellitus.

PMID- 16298615
TI  - Inhibition of p38 mitogen-activated protein kinase protects human islets from
      cryoinjury and improves the yield, viability, and quality of frozen-thawed
      islets.
AB  - The development of an optimal islet cryopreservation method will permit
      transplantation of islets from multiple donors in a single procedure and
      contribute to alleviation of the islet shortage. In this study, we have improved
      human islet cryopreservation methods under serum-free conditions using an
      intracellular-based islet cryopreservation solution (ICS), especially
      supplemented with a p38 pathway inhibitor (p38IH) to suppress p38 mitogen
      activated protein kinase (MAPK) activation. Three different solutions were
      compared for freezing and thawing of human islets (1) conventional RPMI1640
      medium, (2) ICS, and (3) ICS supplemented with a p38IH, SD-282 (ICS-p38IH). Islet
      cryopreservation with ICS-p38IH significantly improved islet recovery, viability,
      and quality after thawing of cryopreserved islets. This improvement may allow the
      use of cryopreserved islets in clinical islet transplantation.

PMID- 16298616
TI  - The start of an islet transplantation program in Japan.
AB  - In Japan, pancreas donation had become possible from cadaveric donor sources,
      both heart-beating or non-heart-beating (NHB). Pancreas allografts have been
      distributed in the organ allocation system of the Japan Organ Transplant Network.
      Meanwhile, islet transplantation has been categorized as a tissue
      transplantation; it is free from legal restraints. Thus, pancreata for islet
      isolation must be obtained from NHB donors. Herein we report the starting program
      and preliminary results of islet transplantation in Japan. Selection and listing
      criteria for transplantation include regional priority, ABO blood type, previous
      islet transplant status with insulin independence, and a longer waiting time.
      Five institutes in Japan (Fukushima, Chiba, Kyoto, Kobe, and Fukuoka) are
      prepared to start programs. A two-layer cold storage method using
      perfluorocarbons and UW solution is recommended for pancreas preservation. Islet
      isolation and purification procedures are performed according to institute
      specific protocol. Immunosuppression is based on sirolimus/tacrolimus combined
      with basiliximab induction. Two or three consecutive infusions of >5000 IE/kg are
      planned for each recipient until achieving insulin independence. Twenty-seven
      isolations and 14 transplants were performed in eight non-insulin-dependent
      diabetes mellitus (IDDM) recipients. Almost all (26 of 27) were NHB donors. All
      recipients are free from hypoglycemic episode after transplantation. One of these
      recipients is insulin independent; the others are currently on minimal doses of
      exogenous insulin. The feasibility of islet transplantation using NHB donors was
      confirmed using a two-layer cold storage method and a steroid-free
      immunosuppressive protocol, with a high rate of graft function.

PMID- 16298617
TI  - Insulin independence of unstable diabetic patient after single living donor islet
      transplantation.
AB  - BACKGROUND: Current success in islet transplantation will lead to a donor
      shortage. Living donor islet transplantation could be an alternative approach to
      expand the potential donor pool. In this study we describe the first successful
      living donor islet transplantation for unstable diabetes, performed at Kyoto
      University Hospital on January 19, 2005. METHODS: The donor was a healthy 56-year
      old woman and mother of the recipient. The recipient was a 27-year-old woman with
      insulin-dependent diabetes since the age of 15 years. She experienced frequent
      hypoglycemic unawareness episodes. Her blood glucose concentration was difficult
      to control and C-peptide level was negative after glucagon stimulation. She
      needed an average 28 of units of insulin per day. The donor underwent a distal
      pancreatectomy and islets were isolated from the resected pancreas graft. The
      total islet yield was 408,114 islet equivalents and isolated islets were
      immediately transplanted into the recipient's liver. RESULTS: After transplant,
      the blood glucose level of the recipient was tightly controlled without
      hypoglycemic episodes. She was discharged on day 37 with a normal oral glucose
      tolerance test (OGTT). The recipient remained insulin-independent for >3 months,
      since day 22 posttransplant. The donor's postoperative clinical course was
      uneventful. She was discharged on postoperative day 18 and returned to her job
      within 1 month. CONCLUSIONS: We report the first successful living donor islet
      transplantation for the treatment of unstable diabetes. We believe that living
      donor islet transplantation may become an option in the treatment of insulin
      dependent diabetes.

PMID- 16298618
TI  - Successful islet transplantation from a single pancreas harvested from a young,
      low-BMI, non-heart-beating cadaver.
AB  - BACKGROUND: Young donors, donors with low body mass index (BMI), and non-heart
      beating (NHB) donors are considered nonideal for islet transplantation. In this
      report, we successfully used a pancreas from a young, low-BMI, NHB donor for
      islet transplantation. METHODS: The donor was a 15-year-old adolescent boy whose
      cause of death was rupture of a primary brain tumor. According to Japanese
      regulations, his pancreas was procured after cardiac arrest. Warm ischemic time
      was 3 minutes and cold ischemic time was 300 minutes. The pancreas was digested
      by the automated method of Ricordi, followed by purification using continuous
      Euro-Ficoll gradients on a Cobe 2991 device. The recipient was a 35-year-old
      woman with unstable type 1 diabetes mellitus. Her pretransplant C-peptide level
      was null. She suffered frequent hypoglycemic unawareness. Her pretransplant M
      value, which is a good marker for glucose instability, was 125. Islet yield was
      252,816 IEQ. There were no signs of contamination. Viability of islets assessed
      by FDA/PI staining was 83%. Stimulation index was 2.7. RESULTS: The patient
      received 5160 IEQ/kg of islets via the portal vein under local anesthesia. There
      were no transplant-related complications. Although she required minimal exogenous
      insulin, her C-peptide level increased to 0.7 ng/mL at postoperative day (POD)
      14. Her M value at POD 15 to 19 decreased dramatically to 23.6, indicating good
      glycemic control. At 3 months posttransplant, episodes of hypoglycemia
      disappeared. CONCLUSIONS: Although an additional transplant is mandatory to wean
      patients from insulin, this case shows the possibility of using marginal donors,
      such as a young, low-BMI, NHB donor, for pancreas islet transplantation.

PMID- 16298619
TI  - C-peptide and glucose values in the peritransplant period after intraportal islet
      infusions in type 1 diabetes.
AB  - BACKGROUND: Successful islet allograft transplantation has been achieved
      worldwide. This study aimed at evaluating the relationship between peritransplant
      C-peptide (CP) values and long-term allograft function. METHODS: We measured CP
      to-glucose ratio (CPGR) in intraportal samples pre- and postinfusion, and in
      peripheral circulation at baseline pretransplant and at 1, 3, 6, 12, 72 hours, 1
      week, and 15 and 30 days after first and second infusion in 13 islet allograft
      recipients. Peritransplant treatment included intravenous (IV) 5% dextrose in
      saline in all patients. We compared portal CPGR to insulin reduction (%) at 30
      days after each infusion, and at 1 year after second infusion. RESULTS: CPGR
      peaked between the immediate postinfusion and 3 hours and decreased at 12 hours.
      At 1 week, CPGR was 0.76 +/- 0.45 and 1.44 +/- 0.37 after first and second
      infusion, respectively. CPGR at 30 days after second infusion doubled compared to
      first infusion (P < .001). There was no correlation between peak CPGR and insulin
      reduction percent at any time point. One patient experienced hypoglycemia (47
      mg/dL) 1 hour after second infusion. CONCLUSIONS: There was no relationship
      between the CP values in the peritransplant period and long-term graft function
      or success rate. The early peak in the C-peptide levels is indicative of a
      significant insulin release after each islet infusion. For this reason, it is
      important to carefully monitor serum glucose levels in the peritransplant period
      (hourly for the first 6 hours) and to maintain an IV glucose infusion to avoid
      hypoglycemia.

PMID- 16298620
TI  - Simple evaluation of engraftment by secretory unit of islet transplant objects
      for living donor and cadaveric donor fresh or cultured islet transplantation.
AB  - BACKGROUND: Evaluation of engraftment is important to assess the success of islet
      transplantation. Recently we developed secretory unit of islet transplant objects
      (SUITO) index for simple evaluation of engraftment. Assuming that normal subjects
      aged <40 years have 100% pancreatic beta-cell function, SUITO index was
      calculated by the formula: 1500 x fasting C-peptide immunoreactivity
      [ng/dL]/(fasting blood glucose [mg/dL] - 63). In this study, we compared the
      efficacy of islet transplantation from cadaveric and living donors using the
      SUITO index. METHODS: We performed eight islet transplantations with non-heart
      beating donors (NHBDs) into five patients. Two patients received fresh islets
      once, one patient received fresh islets twice, one patient received cultured
      islets once, and one patient received cultured islets twice plus fresh islets
      once. In addition, one patient received fresh islets from a living donor. We
      calculated the SUITO index from postoperative days 3 to 30 for each case.
      RESULTS: Mean SUITO index after one fresh islet transplant was 11.7 +/- 1.0,
      after two fresh islet transplants was 28.5 +/- 3.4, after one cultured islet
      transplant was 2.1 +/- 0.4, after two cultured islet transplant was 12.1 +/- 1.9,
      and after two cultured islet transplant plus one fresh islet transplant was 26.7
      +/- 1.7. The mean SUITO index after single living donor islet transplant was 40.7
      +/- 2.6, which was significantly higher compared with all other groups. Insulin
      independence was obtained when the SUITO index was >26, which might reflect that
      26% beta-cell mass was required for insulin independence. CONCLUSION: SUITO index
      is useful to evaluate islet engraftment and to predict the possibility of insulin
      independence.

PMID- 16298621
TI  - Development of anti-human leukocyte antigen class 1 antibodies following
      allogeneic islet cell transplantation.
AB  - Currently there is minimal concern that islet allograft failure could result from
      the development of anti-human leukocyte antigen (HLA) antibodies reactive to the
      allograft. We report here a case of islet allograft failure where the recipient
      developed immunoglobulin G anti-HLA class I antibodies reactive to HLA antigens
      present in two of the three islet cell donors. The patient had no detectable anti
      HLA antibodies prior to the transplant but these antibodies were detected
      approximately 4 months posttransplant. Of concern, these antibodies developed
      despite induction with anti-IL2R antibodies (Zenapex) prior to intraportal islet
      cell infusion, low-dose tacrolimus (12-hour troughs 3 to 5 ng/mL) and rapammune
      (target troughs 12 to 15 ng/mL). The patient was not presensitized with blood
      products or a previous allograft. Her husband, however, shared antigens present
      in one of the islet donors and the recipient could have been presensitized to her
      husband during her two pregnancies. This case clearly demonstrates that islet
      allografts can lead to development of anti-HLA antibodies, which can cause islet
      allograft failure, as is the case with solid organ transplants, and hence
      emphasizes the need to monitor for such antibodies pre- and posttransplant.
      Additionally it appears that currently recommended immunosuppression may not be
      sufficient to inhibit a humoral response to both alloantigens and autoantigens.

PMID- 16298622
TI  - OP-142 gene expression profile of nonfunctional human pancreatic islets:
      predictors of transplant failure?
AB  - Islet culture has become a standard part of most successful protocols for
      clinical islet transplantation. To date, however, islets are transplanted based
      on crude measures of viability, purity and in vitro insulin production without
      adequate prior assessment of the potential for in vivo function. The purpose of
      this study was to define the gene expression profiles of human islets associated
      with in vivo function using a nonimmune NOD-scid mouse model. Human islets from
      eight isolations were maintained in culture for 7 to 14 days in Memphis serum
      free media until transplanted. The RNA was extracted from 10,000 IEQ using
      RNASTAT-60. The gene expression profiles were analyzed using high-density
      Affymetrix U133A GeneChips and Genespring software. An aliquot of 2000 IEQ from
      each islet preparation was also transplanted into NOD-scid animals (n = 5) for in
      vivo function assessments. Islet function was assessed by measurements of human C
      peptide at days 7 and 14 posttransplant. Human C-peptide levels were determined
      by radioimmunoassay. Gene analysis of nonfunction islets (4 of 8 islet
      preparations) showed high relative levels of expression of proinflammatory genes
      and low relative levels of genes directed toward insulin processing and secretion
      as well as islet integrity. Overexpression of hypoxia and proinflammatory genes
      may result in reduced insulin secretion and lead to islet destruction
      posttransplantation. Identifying and validating those genes could allow the
      development of a potency assay for human transplantation that would be very
      useful for screening human islet preparations before clinical transplant.

PMID- 16298623
TI  - Comparison of the collagen VI content within the islet-exocrine interface of the
      head, body, and tail regions of the human pancreas.
AB  - Efficient islet isolation depends on the use of collagenase to digest the
      extracellular matrix within the islet-exocrine interface, the molecular structure
      of which is poorly understood. Recently it has been reported that transplantable
      yields of islets can be isolated from the tail segment of the pancreas alone.
      This study aimed to quantify and compare the amount of collagenase-resistant
      collagen VI within the islet-exocrine interface of the head, body, and tail of
      the human pancreas. Human adult pancreata (n = 5) were retrieved from heart
      beating donors (age range, 40-62 years; cold ischemia times <10 hours). Tissue
      blocks from the head, body, and tail region of each pancreas were fixed in
      formalin and processed for immuno-labelling of collagen VI, which was quantified
      in the islet-exocrine interface using a Zeiss KS-400 image analysis system. Data
      were expressed as area of collagen at the interface relative to the islet area.
      Statistical analysis was done using paired t test. The mean islet areas in the
      head, body, and tail regions were not significantly different. Collagen VI was
      uniformly present within the islet-exocrine interface of all regions of the
      pancreas and was 0.326 +/- 0.064, 0.324 +/- 0.060, and 0.334 +/- 0.052
      microm(2)/islet area (P = .441) in the head, body, and tail, respectively. The
      content of collagen VI within the islet-exocrine interface was uniform throughout
      all parts of the adult pancreas. Targeting this collagen subtype with novel
      collagenase blends may result in consistently improved islet yields and enable a
      wider number of available donor pancreata to be used.

PMID- 16298624
TI  - Pretransplant islet culture: a comparison of four serum-free media using a murine
      model of islet transplantation.
AB  - INTRODUCTION: Human islet transplant protocols frequently incorporate a brief
      period of islet culture before transplantation. The optimal medium for
      pretransplant islet culture is unknown. METHODS: We compared four serum-free
      media formulated for human islets: Miami (MM1), Memphis (M-SFM), Edmonton (EDM),
      and hCell OCZEM-SF/AF (hCell). Islets isolated from a single human pancreas with
      purity >80% were cultured in 2500-islet-equivalent (IE) fractions using the media
      listed. After 7 days, each 2500-IE fraction was grafted under the kidney capsule
      of a streptozocin-diabetic rag1 mouse (n = 4 per group). Mice were evaluated with
      serum glucose monitoring, stimulated C-peptide release, and glucose tolerance
      tests. Islet fractions transplanted immediately after isolation (n = 4 mice)
      served as controls. In vitro islet function was assessed on days 0 and 3 and
      included insulin release (after static glucose stimulation), total cellular C
      peptide content, cell count, and viability. RESULTS: Glucose control was improved
      in all cohorts of mice after transplant, but only islet grafts cultured in MM1
      were statistically indistinguishable from fresh islets. MM1- and hCell-cultured
      islet grafts showed improved glucose tolerance compared with fresh islets; C
      peptide release was similar among the four cohorts. In vitro, only islets
      cultured in MM1 had similar stimulation index to fresh islets, whereas only hCell
      and MM1-cultured islets demonstrated recovery of C-peptide content and insulin
      release. CONCLUSIONS: Media choice before transplant can influence islet quality,
      even when culture periods are short. Miami MM1 and hCell media may provide better
      islet protection than alternative media.

PMID- 16298625
TI  - Adjustment of the ratio between collagenase class II and I improves islet
      isolation outcome.
AB  - BACKGROUND: Previous studies have clarified the distinct roles of collagenase
      class I (ccI) and class II (ccII) in enzymatic release of islets from pancreatic
      tissue. The present study sought to enhance the limited knowledge about the
      optimal ratio between collagenase classes. METHODS: Rat islets were isolated
      utilizing 0.4 DMC-U of neutral protease and 20 PZ-U of fractionated NB-1
      collagenase recombined to obtain a ccII/I ratio of 0.5, 1.0, and 1.5. Quality
      control included assessment of yield (islet equivalents), trypan-blue exclusion,
      insulin release during static glucose incubation, and transplant function in
      diabetic nude mice. Data are expressed as mean values +/- SEM. RESULTS: Digestion
      time was only minimally influenced by different ccII/I ratios. The highest islet
      yield (P < .05) was obtained using a ccII/I ratio of 1.0. Purity and glucose
      stimulation index were only marginally affected by different ccII/I ratios. A
      significant loss of islet viability after 24-hour culture (P < .05) was observed
      only in islets isolated by means of a ccII/I ratio of 0.5 and 1.5 but not 1.0.
      Transplantation into diabetic nude mice revealed sustained islet graft function
      in all experimental groups. CONCLUSIONS: The present study indicates that the
      ratio between ccII and ccI is of significant relevance for optimizing islet yield
      and viability.

PMID- 16298626
TI  - Protection from ischemic cell death by the induction of cytoglobin.
AB  - Methods to reduce beta-cell loss after islet isolation and transplantation must
      be developed if islet transplantation is to become a preferred treatment for
      diabetes. Most recent research has focused on the reduction of toxicity from
      immunosuppressants and the enhancement of revascularization by growth factors
      such as vascular endothelial growth factor. Cytoglobin is an intracellular oxygen
      binding protein found in islet beta-cells, inducible by hypoxia. It is our
      hypothesis that cytoglobin induction and overexpression may improve survival and
      function of transplanted islets by preventing ischemic cell death. Lewis rat
      islets and MIN6 cells were transfected with the cytoglobin gene. Control and
      transfected cells and islets were held for 4 hours at 20% oxygen before glucose
      challenge. Another group of islets and cells was held for 4 hours at 20% and then
      1% oxygen prior to glucose challenge. Untreated or transfected Lewis rat islets
      (n = 800) were transplanted beneath the renal capsule of streptozotocin diabetic
      Lewis rats. In another study, Sprague-Dawley islets were transfected and
      transplanted into streptozotocin diabetic Lewis rats. Fasting blood glucose was
      used as an indicator of islet function and survival. Cytoglobin transfected
      islets and cells retained the ability to secrete insulin at low oxygen
      concentrations in contrast to controls. Cytoglobin over expression reduced the
      development of central islet necrosis after 5 days in tissue culture. Cytoglobin
      inhibited the onset of immunorejection (14 +/- 2 days) as compared with controls
      islets (5 +/- 2 days). Cytoglobin induction may be a useful adjunct to islet
      transplantation.

PMID- 16298627
TI  - In vitro assessment of pancreatic islet vitality by oxymetry.
AB  - In order to assess the quality of freshly isolated and cultivated pancreatic
      islets designed for experimental transplantation in rats we combined the vitality
      staining test, in vitro measurement of insulin secretion capacity, and assessment
      of islet respiration. Oxygen consumption was measured using the respirometer
      Oxygraph 2K equipped with polarographic oxygen sensors. The results of oxymetry
      demonstrated a linear correlation between islet number and oxygen consumption.
      Respiration per unit of viable islet tissue was constant. Oxygen consumption
      tests were in good correlation with the results of insulin release assays, with a
      correlation coefficient of 0.82. We found no significant differences in all three
      vitality-testing methods performed with fresh and 24-hour cultivated islets (P >
      .05). We conclude that polarographic oxymetry provides a fast and easy evaluation
      test of islet quality. After appropriate standardization, the oxymetric technique
      can be used for routine clinical pretransplant islet quality testing. In
      addition, cell membrane integrity and mitochondrial function could be assessed
      after addition of specific respiration inhibitors or stimulators.

PMID- 16298629
TI  - Sirolimus inhibits platelet-derived growth factor-induced collagen synthesis in
      rat vascular smooth muscle cells.
AB  - Vascular smooth muscle cell (VSMC) proliferation and extracellular matrix (ECM)
      accumulation play key roles in the development and the progression of vascular
      remodeling such as transplant arteriosclerosis and restenosis. The present study
      examined the effects of sirolimus (SRL) on platelet-derived growth factor (PDGF)
      induced fibronectin secretion, collagen synthesis, and the related signaling
      pathways including reactive oxygen species (ROS) and mitogen-activated protein
      kinases (MAPK) in rat VSMCs. Primary rat VSMCs were isolated from male Sprague
      Dawley rats. Growth arrested, synchronized cells were treated with various
      concentrations of SRL before the addition of PDGF at 10 ng/mL. Proliferating cell
      nuclear antigen expression, fibronectin secretion, and the activation of
      extracellular signal-regulated protein kinase (ERK) and p38 MAPK were assessed by
      Western blot analysis, collagen synthesis by [(3)H]-proline incorporation, and
      cellular ROS by flow cytometry. PDGF (10 ng/mL) increased VSMC proliferation by
      1.7-fold, fibronectin secretion by 1.5-fold, collagen synthesis by 2.1-fold,
      cellular ROS by 1.6-fold, and activation of ERK and p38 MAPK by 3.3- and 3.9-fold
      compared to controls. SRL above 1 nmol/L inhibited PDGF-induced VSMC
      proliferation and collagen synthesis but not PDGF-induced fibronectin secretion,
      cellular ROS, and activation of ERK and p38 MAPK. These data demonstrated that
      PDGF increased ECM synthesis as well as proliferation through cellular ROS and
      subsequent MAPK activation and that SRL inhibited PDGF-induced VSMC proliferation
      and collagen synthesis in a cellular ROS- and MAPK activation-independent way.

PMID- 16298628
TI  - Protective effect of a radical scavenger, MCI-186 on islet cell damages induced
      by oxidative stress.
AB  - Oxidative stress generated during islet isolation and transplantation causes
      islet cell damage. These oxidative injuries are mediated by reactive oxygen
      species (ROS) and reactive nitrogen species (RNS). MCI-186 is an antioxidant used
      for clinical treatment of cerebral infarction in Japan. We examined a possible
      protective effect of MCI-186 on islet cells against oxidative stress. Islets
      isolated from Sprague-Dawley rats by collagenase P digestion were purified by
      density gradient centrifugation with Ficoll. Islets were treated with hydrogen
      peroxide (H(2)O(2); 5 to 250 micromol) in the presence or absence of MCI-186.
      Cell death was measured by an LDH release assay. Maximum islet cell death was
      observed at 250 micromol of H(2)O(2). MCI-186 inhibited islet cell death in a
      dose-dependent manner with significant reduction above 30 micromol. From the
      results observed we suggest that the antioxidant effects of MCI-186 may prove
      beneficial to improve the preservation of islet cells.

PMID- 16298630
TI  - Effects of heme oxygenase-1 transgenic islets on transplantation.
AB  - Heme oxygenase-1 (HO-1) has been described as a protein capable of cytoprotection
      via radical scavenging and apoptosis prevention. The aim of this study was to
      analyze whether HO-1 overexpression in freshly isolated murine transgenic islets
      resulted in cell protection and improved in vivo functional performance after
      transplantation. We produced transgenic mice in which the human HO-1 transgene
      driven by chicken beta-actin promoter was expressed in the heart, liver, spleen,
      lung, kidney, muscle, intestine, and pancreas in Balb/c mice. One hundred fifty
      islets isolated from HO-1 transgenic and control Balb/c mice were syngeneically
      transplanted under the left kidney capsule of the streptozotocin-diabetic Balb/c
      mice. The recipients who underwent transplantation with HO-1 transgenic islets
      showed higher blood glucose than those with control islets at 4 weeks (320 +/- 25
      vs 189 +/- 43 mg/dL; P < .05). Body weight was not significantly different
      between the 2 groups. Our data indicate transgenic islets with high HO-1
      expression did not improve transplantation outcome.

PMID- 16298631
TI  - Long-term effects of insulin therapy, islet transplantation, and pancreas
      transplantation in the prevention of glomerular changes in kidneys of alloxan
      induced diabetic rats.
AB  - Groups of inbred alloxan-induced diabetic rats were treated with insulin (I),
      islets (IT), or pancreas transplantation (PT). Nondiabetic (N) and untreated
      diabetic (D) control groups were concurrently included. Each group was divided
      into five subgroups of 10 rats and killed after follow-up of 1, 3, 6, 9, and 12
      months. Clinical and laboratory parameters were recorded, and kidney
      ultrastructural and morphometric analyses performed in each 12-month subgroup,
      namely glomerular basement membrane (GM) thickening, podocyte number, and
      number/extension of slit diaphragms (S). Rats from the I group showed poor
      metabolic control of diabetes compared with N group control rats. However,
      successfully transplanted rats (IT and PT) had complete restoration to normal
      levels for all metabolic parameters. GM thickening was significantly higher in
      diabetic compared with control rats. In contrast, the numbers of podocytes and
      slits as well as slit extensions were significantly decreased. Insulin therapy
      did not prevent any alterations upon comparison of diabetic vs control rats.
      Despite good metabolic control in IT rats, the degree of kidney lesion control
      never compared with that achieved in PT rats. In this group all glomerular
      changes were similar to the age-dependent lesions observed in control rats. We
      conclude that either IT or PT may be a good option for diabetes treatment,
      although pancreas transplantation seems to be the most effective treatment to
      control chronic complications.

PMID- 16298632
TI  - Comparative study on biologic and immunologic characteristics of the pancreas
      islet cell between 24 degrees C and 37 degrees C culture in the rat.
AB  - The aim of this study was to investigate the effect of culture at 24 degrees C on
      cell viability, cellular function, immunogenicity, and cytokine profiles of rat
      pancreatic islets. Pancreatic islets were isolated from Lewis rats and cultured
      at either 24 degrees C or 37 degrees C for 14 days. Islet recovery was counted as
      islet equivalents; islet viability was examined with fluorescent vital staining.
      Islet function was measured with a glucose stimulation test. Annexin V, and MHC
      class I and II expression were measured using flow cytometric assay for apoptosis
      and immunogenicity, respectively. Lymphocyte cell proliferation was examined with
      WST-1 proliferation assay. Cytokine profiles were analyzed with quantitative real
      time RT-PCR. All these parameters were measured on 1, 3, 5, 7 and 14 culture days
      after islet isolation. Islet recovery was higher in islets cultured at 24 degrees
      C than 37 degrees C without a change in viability. Insulin secretion after
      glucose stimulation was more effective in 24 degrees C culture conditions.
      Decreased apoptotic cell death was demonstrated in 24 degrees C cultured islets.
      Both MHC class I and II expression on islets and lymphocyte proliferation upon
      coculture with islets were less prominent in 24 degrees C cultured islets. TNF
      alpha expression was lower in islets cultured at 24 degrees C than in islets
      cultured at 37 degrees C. Both IL-1beta and IL-10 cytokine expressions were
      similar under both culture conditions. This study demonstrated that cell recovery
      and function are increased in islets cultured at 24 degrees C than those at 37
      degrees C with decreased antigenicity and proinflammatory cytokine expression.

PMID- 16298633
TI  - Effects of insulin sensitizers on islet transplantation.
AB  - To solve the problems of islet engraftment, we investigated the effects of
      insulin sensitizers, metformin and rosiglitazone, on the in vitro and in vivo
      function of mouse islets. The in vitro study was done by culturing 30 isolated
      C57BL/6 mouse islets with glucose (100 or 300 mg/dL) or rosiglitazone (4.5
      mumol/L) for 2, 4, 8, or 12 hours. The in vivo study was performed by
      syngeneically transplanting 150 C57BL/6 mouse islets under the kidney capsule of
      streptozotocin-diabetic mice. The metformin group was treated with 200 mg/kg/d in
      water and the control group was pair-fed the same volume of liquid diet. In the
      in vitro study, insulin release stimulated by 300 mg/dL glucose (n = 6) was the
      highest at all time points. That stimulated by rosiglitazone (n = 6) was greater
      than by 100 mg/dL glucose (n = 6) only at 8 hours. In the recipients treated with
      metformin (n = 17) and controls (n = 13), the blood glucose decreased and body
      weight increased gradually after transplantation. However, there was no
      significant difference between the two groups. Their tolerance to intraperitoneal
      glucose challenge at 2 and 4 weeks was also comparable. At 4 weeks, 12/17 (71%)
      in the metformin group and 8/13 (62%) in the control group achieved normoglycemia
      (P = .60). At 4 weeks, the insulin content of the graft was 8.35 +/- 3.42 mg in
      the metformin group and 5.28 +/- 4.28 mg in the control group (P = .59). Our data
      indicate that (1) rosiglitazone stimulated isolated islets to release insulin but
      was less effective than high levels of glucose; and (2) metformin treatment had
      no beneficial effect on islet recipients.

PMID- 16298634
TI  - Islet transplantation at subcutaneous and intramuscular sites.
AB  - The subcutaneous site is ideal for clinical islet transplantation because it has
      the advantage of being accessible and can be biopsied when needed. Sadly, the
      results at subcutaneous sites were disappointing. The reason for this failure is
      not known, but poor vascularization may play a role. We tested the hypothesis
      that islet grafts would do better if more vasculature or oxygen could be
      supplied. Six hundred isolated C57BL/6 mouse islets were syngeneically
      transplanted into inbred streptozotocin-diabetic recipients at a subcutaneous
      site on the back with (Group A, n = 6) or without (Group B, n = 8) postoperative
      hyperbaric oxygen (2.4 ATA, 100% O(2)) therapy, or at a calf muscle (Group C, n =
      9). During 13-week posttransplantation follow-up, recipients' blood glucose
      decreased and body weight increased significantly in all 3 groups (P < .05).
      However, there was no significant difference among the 3 groups. At 13 weeks, the
      insulin contents of the graft was also comparable among the 3 groups. Our data
      indicate the following: (1) postoperative hyperbaric oxygen therapy did not
      improve the outcome of islet transplantation at a subcutaneous site; and (2) a
      muscular site was not superior to a subcutaneous site for islet transplantation.

PMID- 16298635
TI  - Effects of intrahepatic canine islet autotransplantation on the portal vein
      pressure and liver function.
AB  - Currently, the most common method used for human islet transplantation is
      intrahepatic implantation via the portal vein, which may affect portal vein
      pressure and liver function. The aim of this study was to investigate the effects
      of intrahepatic canine islet autotransplantation on portal vein pressure and
      liver function. After total pancreatectomy was performed in 30 mongrel dogs,
      islets were isolated and transplanted back into the portal vein of the same dog.
      In our series, 12 dogs achieved normoglycemia (fasting glucose <200 mg/dL)
      without exogenous insulin after transplantation. The portal vein pressure
      increased from 4.6 +/- 1.5 to 7.7 +/- 2.9 cm H(2)O after islet infusion (P <
      .05). Alanine transferase amino transferase (ALT) levels gradually increased
      after pancreatectomy with the peak at 4 weeks after islet infusion. But the
      changes of portal vein pressure and ALT were not significantly different between
      successful and failed islet transplantation. In summary, elevation of portal vein
      pressure and liver enzymes were noted after intrahepatic canine islet
      autotransplantation. However, they did not influence the transplant outcome.

PMID- 16298636
TI  - The importance of pancreatic embryonic epithelium for mesenchyme-to-epithelial
      transition during islet development.
AB  - Stem or progenitor cells are a promising potential alternative source of
      pancreatic islets for transplantation in the treatment of juvenile-onset
      diabetes. However, to derive islets from such cells, it is important to elucidate
      the mechanisms of normal pancreatic development. Previous work in our laboratory
      has shown that, contrary to previous thinking, pancreatic mesenchyme when
      combined with pancreatic epithelium can contribute cells to islets. However, the
      signals and role of individual tissues involved in this mesenchyme-to-epithelial
      transition (MET) have yet to be elucidated. The aim of this study was to
      investigate whether MET can occur in the absence of pancreatic epithelium. Chick
      and quail eggs were incubated for 4 days and the dorsal pancreatic buds and
      stomach rudiments were microdissected. Mesenchyme and epithelium of the organ
      rudiments were separated after collagenase treatment. Separated pancreatic
      mesenchyme were cultured alone and in combination with stomach (nonpancreatic).
      After 7 days of culture, the specimens were analysed using immunohistochemistry
      for quail-specific nucleolar antigen (QCPN), insulin, and islet precursor cell
      marker (ISL-1). Pancreatic mesenchyme when cultured in the absence of epithelium
      did not differentiate into islets, but differentiated into fibroblast-like cells.
      When pancreatic mesenchyme were cultured in combination with stomach epithelium,
      there was no evidence of mesenchymally derived islets. We have demonstrated that
      pancreatic mesenchyme require pancreatic epithelium to differentiate into islet
      cells. These findings further increase our understanding of normal pancreatic
      islet development and may help to elucidate the molecular mechanisms of MET in
      islet development.

PMID- 16298637
TI  - Glucagon expression shift in a syngeneic single-donor intrahepatic rat islet
      transplantation model.
AB  - In the native rat pancreas glucagon is expressed by alpha cells in the outer
      layer of the spheroid islet, producing a circular immunohistochemical staining
      pattern. We asked whether this pattern would remain unchanged after short-term
      and long-term intrahepatic islet transplantation. Islets of inbred Lewis rats
      were isolated with liberase, purified by discontinuous density gradients,
      handpicked, and cultured for 24 hours. After rats were rendered diabetic with
      streptozotocin, islets were implanted intraportally. Transplanted animals were
      sacrificed at 1 to 2 days (n = 5) or 100 days (n = 6). Islet clusters were
      detected by hematoxylen-and-eosin staining. Serial slides were stained for
      glucagon and insulin with the alkaline phosphatase and alkaline phosphate method
      at 1 to 2 days after transplantation islets with strong insulin expression were
      found within the portal vein branches. However, glucagon staining showed an
      incomplete circular staining pattern. After 100 days insulin expression remained
      strong, whereas only few glucagon-expressing cells were detected. Intrapancreatic
      islets showed inversion of the ratio of insulin- to glucagon-positive cells in
      favor of the glucagon-expressing cells that now composed the major part of the
      islet. Streptozotocin had selectively damaged beta cells in the recipient. In
      transplanted islets glucagon expression faded over time, possibly due to a
      functional involution process or to stress/inflammatory mechanisms during the
      isolation, transplantation, and the posttransplantation periods.

PMID- 16298638
TI  - Beneficial effects of nerve growth factor on islet transplantation.
AB  - OBJECTIVE: Development of the Edmonton protocol was a pivotal contribution to
      clinical islet transplantation (ITx). Persistent limitations to ITx include
      insufficient supply and posttransplant functional failure of islets. In this
      study, nerve growth factor (NGF) was used to enhance both cultured and
      transplanted beta-cell function, thus achieving prolonged graft survival.
      METHODS: Fluorescence microscopy with ethidium bromide and SYTO green staining
      was used to evaluate balb/c mouse islet viability. Islets were syngeneically
      transplanted under the kidney capsule of recipients with streptozotocin-induced
      diabetes. Intraperitoneal glucose tolerance was used to test posttransplant
      function. RESULTS: Improved viability was found in murine islets cultured for 48
      hours in 500 ng/mL NGF (P < .05). A submarginal islet mass (260 islet
      equivalents/recipient) was used for ITx. The NGF-culture resulted in prolonged
      islet survival (24.7 days vs 5.5 days without NFG culture, n = 6). Intravenous
      injection of NGF (6 mug) on the day of transplant and postoperative days (POD) 1
      + 2 prolonged islet survival from 4.1 days (no treatment) to 13.2 days (n = 6).
      Glucose tolerance testing performed at posttransplant day 4 showed improvement at
      60 and 120 minutes in recipients treated intravenously with NGF (blood glucose of
      95 +/- 15 vs 210 +/- 78 and 57 +/- 6 vs 176 +/- 70 mg/dL, respectively).
      CONCLUSION: NGF may improve beta-cell function and result in prolonged survival
      of both cultured and transplanted islets.

PMID- 16298639
TI  - Magnetic resonance imaging of intrahepatically transplanted islets using
      paramagnetic beads.
AB  - Superparamagnetic agents can be reliably used for magnetic resonance imaging
      (MRI) of pancreatic islets located in the liver sinusoids. However, the main
      disadvantages seemed to be the rather long culture time necessary for islet
      labeling and the low specificity of these agents. In the present study we
      investigated a more specific approach with a shorter labeling time using
      immunomagnetic particles. Isolated rat islets were cultivated with immunomagnetic
      beads coated with antibody against rat MHC class I antigen. Labeled islets were
      transplanted into the livers of syngeneic rats. The animals were examined weekly
      by MRI or livers explanted 10 minutes after islet transplantation for in vitro
      experiments. In both in vitro and in vivo studies, labeled transplanted islets
      were imaged as hypointensive spots, diffusely distributed throughout the liver.
      This experiment represents an alternative way of islet imaging by magnetic
      resonance, which is as effective as the use of known superparamagnetic contrast
      agents and more specific owing to targeting to specific donor antigens.

PMID- 16298640
TI  - Vitality of pancreatic islets labeled for magnetic resonance imaging with iron
      particles.
AB  - We previously described an in vivo method for pancreatic islet visualization
      using magnetic resonance imaging with the aid of superparamagnetic nanoparticles
      of iron oxide (Resovist) or by magnetic beads precoated with antibodies
      (Dynabeads). The aim of this study was to investigate the in vitro effect of
      islet labeling on their quality. Isolated rat islets were cultivated for 48 hours
      with a contrast agent or, in the case of magnetic antibody-coated beads, for only
      2 hours. The ability to secrete insulin was tested by a static insulin release
      assay and the results were expressed as a stimulation index. Staining with
      propidium iodide and acridine orange was performed to determine the ratio of live
      to dead cells. Stimulation indices in the Resovist islets (n = 23) vs controls (n
      = 14) were 15.3 and 15.0, respectively, and in the Dynabeads islets (n = 15) vs
      controls (n = 12) 21.3 and 19.9, respectively. The vitality of the Resovist
      islets vs controls determined by live/dead cells ratio was 90.8% and 91.1%,
      respectively (n = 20), and in the Dynabeads islets vs controls was 89.4% and
      91.8%, respectively (n = 11). Islet labeling with the contrast agent as well as
      with specific antibodies with iron beads did not change the vitality and insulin
      secreting capacity assessed in vitro (P > .05). Magnetic resonance using iron
      nanoparticles represents the only method for in-vivo visualization of
      transplanted islets so far. Our data represent an important contribution for its
      clinical use.

PMID- 16298642
TI  - Pancreas oxygenation is limited during preservation with the two-layer method.
AB  - BACKGROUND: The two-layer method (TLM) for pancreas preservation reportedly
      improves islet yield and transplantation outcome relative to previous methods.
      Increased ATP concentrations support the hypothesis that these improvements are
      related to better oxygenation from the perfluorocarbon solution. However, there
      are limited direct measurements of oxygen partial pressure, (pO(2)) in pancreata
      preserved with the TLM. Theory predicts that only a small fraction of a human
      pancreas can be oxygenated externally. In this report we examine pancreas
      oxygenation with the TLM using theory and direct pO(2) measurements. METHODS:
      pO(2) profiles in cylindrical pancreata were calculated at various temperatures
      with a diffusion-reaction model. The pO(2) was measured using fiber optic sensors
      in the core of porcine pancreatic tissue preserved with the TLM in media
      saturated with 100% oxygen. RESULTS: The model predicts that at 8 degrees C, even
      in the absence of an external pO(2) gradient, oxygen penetration depth is about 1
      mm and insensitive to pancreas diameter, while the oxygenated volume fraction is
      about 15% for a 2.5-cm-diameter pancreas. Experimental measurements verified that
      pO(2) is virtually zero in the core of a 1-cm-thick pancreatic piece preserved
      with the TLM. Penetration of solution around the sensor may be responsible for
      the observed lag and for the previously reported nonzero pO(2) measurements.
      Reoxygenation of heat-treated tissue took several hours. CONCLUSIONS: The TLM can
      oxygenate only a small volume fraction of a human pancreas. Pancreas oxygenation
      through the native vasculature should be explored to further improve yield of
      viable islets.

PMID- 16298641
TI  - Evaluation of energy state of islet independent of size using a newly developed
      ATP bioluminescence assay.
AB  - ATP content or energy charge (EC) of islets may be a good parameter to assess
      viability. In this study, we examined adenine nucleotides and EC of freshly
      isolated or 24-hour cultured rat islets of various diameters using a novel
      bioluminescent enzymatic cycling assay system. For freshly isolated islets, ATP
      content and islet diameter showed a high correlation (r = 0.842, P < .001), but a
      significant correlation was not observed for cultured islets (r = 0.284) when all
      islets were included for the analysis. When only the cultured islets with a
      diameter <350 microm were included for analysis, a significant correlation was
      observed (r = 0.719). EC of freshly isolated islets fluctuated widely
      irrespective of diameter, in contrast with results of 24-hour cultured islets,
      which showed a stable, high EC, regardless of diameter. These data suggest that
      the ATP content of islets correlates with the islet size and that EC of islets
      widely fluctuates following isolation, indicating a significant role of
      monitoring ATP and EC of islets before transplantation.

PMID- 16298643
TI  - Intraperitoneal alginate-encapsulated neonatal porcine islets in a placebo
      controlled study with 16 diabetic cynomolgus primates.
AB  - BACKGROUND: A nonhuman primate model of diabetes is valuable for assessing
      porcine pancreatic islet transplants that might have clinical benefits in humans.
      METHODS: Neonatal porcine islets, microencapsulated in alginate-polyornithine
      alginate, were injected intraperitoneally (10,000 IEQs/kg islets) into eight
      adult male cynomolgus monkeys rendered diabetic with streptozotocin. Eight
      diabetic controls were given an equivalent dose of empty placebo capsules. All
      subjects received a repeat transplant 3 months after the first. RESULTS: The
      transplant was well tolerated and no adverse or hypoglycemic events occurred.
      There were two deaths from nontransplant treatment or diabetic complications
      unrelated to the transplants. After transplantation, the average insulin dose was
      reduced in the islet-treated group and increased in the control group. At 12
      weeks after the first transplant there was a mean 36% (95% CI: 6% to 65%, P =
      .02) drop in daily insulin dose compared with the control group. After 24 weeks
      the difference increased to a mean of 43% (95% CI: 12% to 75%, P = .01) without
      significant differences in blood glucose values between the two groups.
      Individual responses after islet transplant varied and one monkey was weaned off
      insulin by 36 weeks. At terminal autopsy, organs appeared normal and there was no
      visible peritoneal reaction. No animal had polymerase chain reaction (PCR)
      amplified signals of porcine endogenous retrovirus or exogenous virus infections
      in blood or tissues. CONCLUSION: Repeated intraperitoneal transplantation of
      microencapsulated neonatal porcine islets is a safe procedure in diabetic
      primates. It was shown to result in a significant reduction in insulin dose
      requirement in the majority of animals studied, whereas insulin requirement
      increased in controls.

PMID- 16298644
TI  - An improved method of fluorescent dual insulin and endothelial staining allows
      visualisation of the revascularisation of intraportally transplanted islets.
AB  - BACKGROUND: Intraportally transplanted islets are avascular at the time of
      transplantation and take up to 14 days to fully revascularize, during which time
      up to 60% of islet mass may be lost. To investigate and improve islet
      revascularization, a robust method for the visualization and quantification of
      this process is required. METHODS: Islets isolated from Lewis rats were
      transplanted intraportally into the liver of diabetic syngeneic Lewis recipients.
      The animals were humanely killed either on the day of transplant or at 3, 5, 7,
      or 14 days posttransplant. The harvested livers were sectioned and stained with
      Bandeiraea simplicifolia lectin (for endothelial cells) and anti-insulin antibody
      and counterstained with DAPI. The slides were visualized with a fluorescent
      microscope. RESULTS: Islets were visualized over the whole time course. Insulin
      and endothelial staining was clearly visualized on the day of transplantation,
      but by day 3 endothelial staining was scarce within the islet. By day 5, early
      vessel formation could be seen within the islet, but insulin staining was patchy
      and associated with apoptotic nuclei. By day 7, vessels could be seen throughout
      the islet and insulin staining had returned. Day 14 sections showed a fully
      revascularized islet. CONCLUSIONS: The staining provided good delineation of
      islet endothelium and beta-cell location, with clear observation of the
      revascularization process. This technique also suggests that days 3 through 5 may
      be a critical period for islet survival and provides a good model for studying
      the effects of manipulating the revascularization process.

PMID- 16298645
TI  - Functional assessment of microencapsulated porcine islets with agarose
      polystyrene sulfonic acid in vitro and in xenotransplantation.
AB  - We evaluated the functional efficacy of microencapsulated porcine islet
      xenografts transplanted into nonobese diabetic (NOD) mice. Islets were isolated
      from the pancreata of CSK miniature swine by manual collagenase digestion and
      Ficoll purification. Purified porcine islets were immediately encapsulated into
      microbeads of agarose polystyrene sulfonic acid (Ag-PSSa). They remained
      morphologically intact by dithizone staining after 7 days in culture. Insulin
      secretion from encapsulated islets was determined in response to glucose
      challenge during perifusion. When encapsulated islets were exposed to 200 mg/dL
      glucose, within 5 minutes, insulin release became 5-fold greater than that at 80
      mg/dL. However, a second phase insulin secretion appeared in response to 250
      mg/dL glucose challenge. In xenotransplantation, microencapsulated porcine islets
      (1000 to 1800 MC islets) were transplanted into the peritoneal cavity of diabetic
      NOD mice (n = 4) without immunosuppression. The survival times after the onset of
      diabetes were observed after both MC islets transplanted NOD mice and
      nontransplanted NOD mice (n = 4). MC islets transplant recipients had
      significantly (P < .05) longer survival (47.5 +/- 18.6; mean +/- SD) than
      nontransplanted NOD mice (21.0 +/- 9.31), although random blood glucose levels
      were not normalized.

PMID- 16298646
TI  - Preformed antibodies to alpha1,3-galactosyltransferase gene-knockout (GT-KO) pig
      cells in humans, baboons, and monkeys: implications for xenotransplantation.
AB  - OBJECTIVE: The aim of our study was to determine the prevalence and cytotoxicity
      of primate antibodies directed to antigens other than Galalpha1,3Gal (Gal),
      termed nonGal antigens. METHODS: Sera from human, baboon, and cynomolgus monkeys
      were tested by flow cytometry for IgM and IgG binding to both wild-type (WT) and
      GT-KO pig peripheral mononuclear cells (PBMC). Also, complement-dependent
      cytotoxicity assays were performed. RESULTS: All species demonstrated
      significantly higher antibody binding and cytotoxicity to WT cells compared to GT
      KO cells (P < .01). Cynomolgus monkeys had significantly higher IgM binding to WT
      and GT-KO cells than did baboons or humans (P < .01). Furthermore, approximately
      50% of both human and baboon sera proved to be lytic to GT-KO cells, compared to
      76% of monkey sera (P < .01). CONCLUSIONS: We confirm the advantage of using GT
      KO pig grafts over WT pig grafts. However, our results suggest that, compared to
      the cynomolgus monkey, the baboon may be a more suitable model to study antibody
      mediated rejection of GT-KO pig grafts.

PMID- 16298647
TI  - Role of chemokine signaling pathways in pancreatic islet rejection during allo-
      and xenotransplantation.
AB  - During transplantation, pancreatic islets release chemokines promoting macrophage
      attraction, hampering engraftment of islets. The aim of this work was to examine
      the mechanism of macrophage-pancreatic islets interaction that mediates islet
      rejection during transplantation. Human macrophages exposed to supernates of
      human and porcine pancreatic islets for the allogeneic and xenogeneic models,
      respectively, were evaluated for chemotaxis and expression of chemokine receptors
      (CCR-5). To modulate migration and identify the signaling pathway of macrophages,
      we tested pertussis toxin (PTX) to block Gi protein, and staurosporin and
      wortmannin to inhibit the protein kinase, and phosphoinositol-3 kinase,
      respectively. The addition of these agents significantly reduced macrophage
      migration induced by human islet supernates from 3.2 +/- 0.5 to 1.5 +/- 0.2, 0.9
      +/- 0.1, and 1 +/- 0.1, respectively (P < .001, n = 3). In a xenotransplantation
      model, the reduction was less decreased, from 4.1 +/- 0.4 to 2.7 +/- 0.3 (P <
      .01), to 2.5 +/- 0.3 (P < .01), or to 1 +/- 0.1 (P < .001). Western blot analysis
      of chemokine receptor expression showed increased CCR-5 expression with human
      pancreatic islet supernates. Moreover, decreased islet purity increased CCR-5
      expression. Pharmacologic study showed that PTX induced an increase in CCR-5
      expression in allogeneic transplantation, whereas only staurosporin induced an
      increased receptor expression in the xenogeneic model, suggesting that chemokines
      participate in islet rejection even though the chemokine signaling pathways
      differ between allo- and xenotransplantation. Understanding the molecular
      mechanisms of islet rejection may improve graft survival.

PMID- 16298648
TI  - Effect of stable glutamine compounds on porcine islet culture.
AB  - BACKGROUND: Pig islets are characterized by significant fragility, preventing
      successful islet culture prior to xenotransplantation. To improve outcome after
      culture, we compared the effects of glutamine supplementation on survival and
      viability of isolated pig islets during culture. METHODS: Pig islets were
      suspended in CMRL 1066 supplemented either with 2.5 mmol/L N-acetyl-L-alanyl-L
      glutamine (NALG), a stable compound of L-glutamine, or with 2.5 or 5.0 mmol/L of
      free L-glutamine (L-Glu). After 24 hours of preincubation, islets were stressed
      for additional 48 hours with H2O2, DETA, or a cytokine mix. RESULTS: Twenty-four
      hour survival of unstressed controls precultured with 2.5 mmol/L NALG was
      significantly decreased compared with islets pretreated with 2.5 or 5.0 mmol/L L
      Glu (P < .01). Fresh islets, viability decreased significantly after NALG
      preincubation, but was maintained after preincubation in 2.5 or 5.0 mmol/L L-Glu
      (not significant vs fresh; P < .05 vs NALG). Compared with NALG pretreatment L
      Glu did not significantly ameliorate the relative survival (related to cultured
      controls) of islets during proinflammatory treatment. Nevertheless, the
      beneficial effect of L-Glu preculture on absolute survival (related to freshly
      isolated islets) of stressed islets was still present in contrast to NALG
      pretreatment (P < .01). Viability of stressed islets was significantly protected
      by L-Glu but not by NALG. CONCLUSIONS: Pig islet culture is significantly
      improved if L-glutamine is administered in an unbound form compared with the
      stable compound NALG. Stress resistance of pig islets seems to be increased by
      free L-glutamine as well.

PMID- 16298649
TI  - Follow-up experience using histidine-tryptophan ketoglutarate solution in
      clinical pancreas transplantation.
AB  - In May 2003, at Indiana University, the standard cold preservation solution
      University of Wisconsin (UW) solution was replaced by histidine-tryptophan
      ketogluatarate (HTK) solution. Earlier, we presented our initial experience with
      HTK in pancreas preservation with an analysis of the first 10 pancreas
      transplants. Here we report updated results with HTK in pancreas transplantation
      over the past 18 months. Between May 2003 and March 2005, a total of 87 pancreas
      transplants were performed with 78 of these organs utilizing HTK. Seventy five
      patients received 78 organ transplants. Surgical procedures performed were:
      simultaneous kidney pancreas transplantation (n = 50, 64%), pancreas after kidney
      transplantation (n = 19, 24%), solitary pancreas transplantation (n = 9, 12%).
      Donor and recipient data were collected with primary outcomes as primary
      nonfunction and 30-day graft and patient survivals, and compared to the UW cohort
      from our original report. Donor and recipient demographics were similar. Mean
      follow-up time is 12 +/- 6 months. The mean cold ischemia time was 9 +/- 3 hours.
      There were no cases of primary graft nonfunction. Thirty-day and 1-year patient
      survivals were 99% and 93%. The 30-day and 1-year graft survivals were 96% and
      93%. There were five grafts lost, including three within the first month (two
      venous and one arterial thrombosis). There was one case of chronic rejection and
      one noncompliance. All other patients were insulin-independent by discharge.
      Serum fasting blood glucose and serial amylase remained comparable at all
      intervals posttransplantation. Within this range of cold ischemia time, HTK
      appears to provide effective pancreas preservation.

PMID- 16298650
TI  - Risk factors and outcomes analyses at 36 months of a prospective, randomized,
      multicenter, trial of daclizumab induction in simultaneous kidney-pancreas
      transplant recipients.
AB  - The purpose of this study was to analyze risk factors for acute rejection (AR)
      and long-term outcomes in simultaneous kidney-pancreas transplant (SKPT) patients
      enrolled in a prospective, multicenter study of daclizumab (DAC) versus no
      antibody induction. METHODS: A total of 298 SKPT patients were randomized into
      three groups and categorized based on an intent to treat analysis, and factors
      associated with AR and survival were identified using logistic regression and Cox
      proportional hazards models. RESULTS: There were no differences in patient or
      allograft survival or rejection rates among the three groups at 36 months follow
      up. Delayed (kidney) graft function (DGF) was a risk factor for subsequent kidney
      AR (odds ratio = 2.79, P = .002). The presence of kidney AR was also a risk
      factor (hazard ratio [HR] = 3.1, P = .003) for kidney graft loss, whereas risk
      factors for pancreas graft loss (censored for graft loss within 30 days or death
      with functioning graft) included pancreas AR (HR = 1.97, P = .012), kidney AR (HR
      = 1.61, P = .042), CMV serostatus donor +/recipient - (HR = 1.62, P = .026), and
      HLA-B mismatch (HR = 1.58, P = .01). Kidney graft loss (HR = 5.5, P = .02) was
      the only predictor of mortality. CONCLUSIONS: At 36 months, no significant
      differences in outcomes were noted in the three study groups. DGF was the major
      risk factor for kidney AR, kidney AR was the major risk factor for kidney graft
      loss, and kidney graft loss was the major determinant of mortality. Prevention of
      kidney DGF and AR in SKPT recipients may play a pivotal role in optimizing long
      term outcomes.

PMID- 16298651
TI  - A prospective, randomized, multicenter study evaluating the safety and efficacy
      of two dosing regimens of daclizumab compared to no antibody induction in
      simultaneous kidney-pancreas transplantation: results at 3 years.
AB  - This is a report of outcomes at 36 months of a prospective, multicenter study
      comparing the safety and efficacy of two dosing regimens of daclizumab with no
      antibody induction in simultaneous kidney-pancreas transplant (SKPT) patients
      receiving tacrolimus, mycophenolate mofetil, and prednisone. A total of 298 SKPT
      patients were randomized into one of three groups: daclizumab 1 mg/kg/dose every
      14 days for 5 doses (group 1, n = 107); daclizumab 2 mg/kg/dose for 2 doses
      (group 2, n = 113); and no antibody induction (group 3, n = 78). There were no
      differences in baseline characteristics among the three groups, and results were
      analyzed by an intent-to-treat analysis. The incidence of composite events (acute
      rejection [AR], any allograft lost, or death) at 3 years was 49%, 43%, and 55% in
      groups 1, 2, and 3, respectively (P = .278). The cumulative incidences of AR were
      not statistically different among the three groups (P = .178). The mean time to
      first AR was delayed in groups 2 (288 days) and 1 (245 days) compared to group 3
      (145 days, P = .07). There were no differences in patient or allograft survival
      rates among the three groups, and the rates of serious adverse events,
      infections, and hospital readmissions were also comparable. Excellent dual graft
      function in patients with surviving grafts was observed in all three groups at 3
      years. CONCLUSIONS: The alternative 2-dose regimen of daclizumab was as safe and
      effective as the conventional 5-dose regimen compared to no antibody induction in
      SKPT patients, but no long-term benefits were noted.

PMID- 16298652
TI  - Successful simultaneous kidney-pancreas transplantation from extreme donors.
AB  - The purpose of this study was to retrospectively review our experience with
      "extreme" pancreas donors compared to conventional (CONV) donors. METHODS:
      "Extreme" (EX) pancreas donors were defined as deceased donors (DDs) age >50
      years, <8 years, donation after cardiac death (DCD), and targeted for organ
      discard. RESULTS: From January 2002 through January 2005, we performed 40
      simultaneous kidney-pancreas transplants (SKPT) with Thymoglobulin induction,
      including 9 (22.5%) from EX and 31 from CONV DDs. Mean DD age was higher in EX DD
      (41.2 years EX vs 26.0 CONV, P < .05), but mean recipient age and cold ischemia
      times did not differ between groups. With a mean follow-up of 16.8 months in the
      EX DD group, patient and kidney graft survival rates are both 100%, and the
      pancreas graft survival rate is 89%. With a mean follow-up of 21.7 months in the
      CONV DD group, patient and kidney graft survival rates are both 93.5% and the
      pancreas graft survival rate is 77.4%. All patients with surviving grafts
      exhibited good initial (1 case of delayed kidney graft function in a CONV DD) and
      stable long-term kidney and pancreas graft function. Mean length of initial
      hospital stay and the incidences of acute rejection, readmissions, operative
      complications, and infections were similar between groups. CONCLUSIONS: The
      results of this study suggest that the limits of donor acceptability continue to
      evolve as excellent outcomes can be achieved in SKPTs from selected EX DDs.

PMID- 16298653
TI  - A pilot study of immunosuppression minimization after pancreas-kidney
      transplantation utilizing thymoglobulin induction and sirolimus maintenance
      therapy.
AB  - AIMS: To determine outcomes utilizing thymoglobulin and sirolimus
      immunosuppression, with early steroid withdrawal in low-immune responder pancreas
      kidney (SPK) recipients, and conversion from cyclosporine (CsA) to mycophenolic
      acid (MPA) in all recipients at 6 months posttransplantation. METHODS: SPK
      recipients received thymoglobulin, sirolimus, and reduced-dose CsA
      immunosuppression. Low immune responders (non-African-Americans with a
      pretransplant PRA < 30%) were withdrawn from prednisone on posttransplant day 5
      and high immune responders were continued on prednisone. All recipients were
      converted from CsA to MPA at 6 months posttransplantation. During conversion,
      recipient immune response was monitored by flow PRA and a T-cell stimulation
      assay (Cylex). RESULTS: With a mean follow-up of 9 +/- 4 months, one pancreas was
      lost to pancreatitis, with no patient or kidney losses and no acute rejection
      episodes. All eight low immune responder patients were steroid-free at 9 +/- 5
      months posttransplantation. Seven patients (five low and two high immune
      responders) with at least 6-month follow-up were converted from CsA to MPA. One
      high immune responder with a pretransplant PRA of 43% remained with a PRA of 53%
      +/- 2% postconversion. The second high immune responder had a pretransplant PRA
      of 34% and a postconversion PRA of 0%. The five low immune responders had a mean
      pretransplant PRA of 16% +/- 15% and a postconversion PRA of 0% (P < .01). The
      Cylex assay resulted in 67% low responsiveness for both high and low immune
      responders. CONCLUSION: Thymoglobulin induction with sirolimus maintenance
      therapy permitted immunosuppression minimization in selected pancreas transplant
      recipients. Posttransplant evaluation revealed a diminished (regulated) immune
      response in six of seven patients.

PMID- 16298654
TI  - Experience with sirolimus for calcineurin minimization/elimination in pancreas
      after-kidney transplantation.
AB  - Pancreas after kidney (PAK) transplantation, associated with a persistent
      elevation in serum creatinine (defined as a >25% increase from baseline), was
      seen in 7 of 11 (64%) cases maintained on immunosuppressive therapy consisting of
      tacrolimus, mycophenolate mofetil, and prednisone. Patients were converted to
      sirolimus as a means of minimizing or eliminating exposure to tacrolimus, the
      presumed nephrotoxic agent. With the use of sirolimus-based immunosuppression,
      and with elimination or minimization of tacrolimus, renal function, as measured
      by serum creatinine, stabilized or improved in all cases.

PMID- 16298655
TI  - Metabolic effect of sirolimus versus mycophenolate mofetil on pancreatic graft
      function in the early posttransplant period.
AB  - Metabolic effects of immunosuppressive agents are of great importance in pancreas
      or islet transplantation. The aim of our study was to compare effects of
      tacrolimus-based immunosuppression in conjunction with sirolimus (RAPA) versus
      mycophenolate mofetil (MMF) on glucose metabolism in type 1 diabetic recipients
      following a simultaneous pancreas and kidney transplantation (SPK). We examined
      30 insulin-independent patients after SPK with venous systemic drainage of the
      pancreatic graft. All recipients had good kidney graft function. Fasting
      glycemia, insulin levels, glycosylated hemoglobin (HbA(lc)), standard intravenous
      glucose tolerance test (IVGTT), and trough RAPA levels were assessed in pancreas
      recipients before elective steroid withdrawal. Insulin sensitivity was evaluated
      using the homeostasis model assessment (HOMA-IR). The groups did not differ in
      age, BMI, posttransplant period, steroid daily dose, HbA(lc), and fasting
      glycemia. We did not find any significant difference in the IVGTT response. Area
      under the curve of insulin levels during IVGTT and HOMA-IR were significantly
      lower in the RAPA group. Trough levels of RAPA had no significant impact on any
      of the examined parameters. Glucose tolerance measured with the use of IVGTT was
      similar in patients treated with RAPA and MMF. However, recipients on sirolimus
      treatment had significantly lower insulinemia during the test and consequently
      more favorable indices of insulin action as assessed by HOMA-IR.

PMID- 16298656
TI  - Experience with alternate-day thymoglobulin induction in pancreas transplantation
      with portal-enteric drainage.
AB  - The purpose of this study was to retrospectively review outcomes in patients
      undergoing pancreas transplantation (PTX) with a novel induction protocol of
      alternate-day thymoglobulin (rATG) in combination with tacrolimus (TAC),
      mycophenolate mofetil (MMF), and steroids. From January 2002 through January
      2005, we performed 55 PTXs in 53 patients. The first dose of rATG (1.5 mg/kg) was
      given intraoperatively, and subsequent doses were given on alternate days until
      therapeutic TAC levels (>8 ng/mL) were achieved. All patients underwent PTX with
      enteric drainage, including 51 with portal and 4 with systemic venous drainage.
      Patients received a minimum of 2 and maximum of 6 doses of rATG induction (median
      3 doses). The patient group had a mean age of 42.8 years and included 40
      simultaneous kidney-PTX, 11 sequential PTX after kidney, and 4 PTX-alone
      transplant recipients. Patient, kidney, and pancreas graft survival rates are
      96%, 96%, and 84%, respectively, with a mean follow-up of 21 months. The
      incidence of acute rejection was 18%; there were no graft losses due to isolated
      acute rejection. The incidence of infection was 60%, but there were no cases of
      polyomavirus or Epstein-Barr virus infection and only 6 cases (11%) of
      cytomegalovirus infection. The composite endpoint of no rejection, graft loss, or
      mortality was attained by 71% of patients. At present, 94% of surviving patients
      are both dialysis and insulin-free, including 5 successful PTX retransplants.
      These findings suggest that PTX with portal-enteric drainage and alternate day
      rATG induction may result in excellent intermediate-term outcomes.

PMID- 16298657
TI  - Impact of the metabolic syndrome on long-term outcomes in simultaneous kidney
      pancreas transplantation.
AB  - The metabolic syndrome (MS) has been implicated as an important nonimmunologic
      risk factor for chronic renal transplant dysfunction. The aim of this study was
      to determine the impact of the MS on outcomes in simultaneous kidney-pancreas
      transplantation (SKPT). Data were available on 241 patients enrolled in a
      prospective, multicenter randomized study of daclizumab compared with no antibody
      induction in SKPT. Presence of MS before and after SKPT was defined using NCEP
      ATP III (National Cholesterol Education Program Adult Treatment Panel III)
      criteria. Body mass index (BMI) was used as a surrogate for waist circumference.
      MS was present in 59% of patients pretransplantation but only in 19% of patients
      1 year after SKPT (P < .0001). Demographic and transplant characteristics were
      well matched for those with MS (MS+) and without MS (MS-) at 1 year. Presence of
      MS at 1 year was associated with the following changes at 3 years: increased
      serum creatinine level (1.65 mg/dL MS- vs 2.05 mg/dL MS+; P = .13); decreased
      modification of diet in renal disease calculated glomerular filtration rate (GFR;
      58 mL/min MS- vs 48 mL/min MS+; P = .02); increased HgbA1C level (5.6% MS- vs
      6.6% MS+; P < .001); and lower pancreas graft (PG) survival rate (88% MS- vs 71%
      MS+; P = .01). Linear regression analysis identified MS+ and the subgroup of MS+
      without functioning PG at 1 year as independent risk factors for renal
      dysfunction, whereas MS+ with functioning PG at 1 year was not a risk factor for
      renal dysfunction. Presence of MS at 1 year is associated with long-term renal
      dysfunction after SKPT. Efforts to decrease early PG failure may help mitigate
      against MS-associated renal dysfunction.

PMID- 16298658
TI  - Inferior late functional and metabolic outcomes in African American simultaneous
      kidney-pancreas recipients.
AB  - The aim of this study was to determine the impact of ethnicity on the major
      endpoints of a prospective, multi-center, randomized trial of 2 dosing regimens
      of daclizumab compared with no antibody induction in simultaneous kidney-pancreas
      transplantation (SKPT). A total of 298 patients were randomized into 3 groups:
      daclizumab 1 mg/kg/dose every 14 days for 5 doses (Group I, n = 107), daclizumab
      2 mg/kg/dose every 14 days for 2 doses (Group II, n = 113), and no antibody
      induction (Group III, n = 78). All patients received tacrolimus (TAC),
      mycophenolate mofetil (MMF), and steroids. Thirty-seven patients (12.4%) were
      African American (AA) and 261 were non-African American (NAA). Demographic and
      transplant characteristics were comparable between AA and NAA patients. At 3
      years, there were no differences in patient, kidney, or pancreas graft survival
      rates. Rejection rate was similar between AA and NAA. Although mean serum
      creatinine (SCr) levels at 1 year were comparable between AA and NAA patients (AA
      1.5 mg/dL vs NAA 1.3 mg/dL; P = .23), by 3 years AA patients had higher mean SCr
      levels (AA 2.1 mg/dL vs NAA 1.5 mg/dL; P < .0001) and lower calculated glomerular
      filtration rate (GFR) (AA 45 mL/min vs NAA 56 mL/min; P = .01). Mean HgbA1C,
      total cholesterol, and diastolic blood pressure (BP) were higher in AA patients
      at 3 years, compared with NAA patients. In conclusion, in this study, AA patients
      had worse late functional and metabolic outcomes after SKPT compared with NAA
      patients. Further longitudinal follow-up is needed to determine the ultimate
      impact of these findings on long-term patient and graft survival.

PMID- 16298659
TI  - Surgical complications of simultaneous pancreas-kidney transplantation: a 16-year
      experience at one center.
AB  - Fifty-one simultaneous pancreas-kidney transplants (SPKT) were performed between
      1988 and 2004 in patients of mean age 34 years and 23 years duration of diabetes
      treatment. All kidney and pancreas recipients were on maintenance hemodialysis
      therapy prior to SPKT. The pancreas with duodenal segment and the kidneys were
      harvested from cadaveric heart-beating donors. Cold ischemia time in UW solution
      varied from 4 to 14 hours (mean, 9 hours 35 minutes). Twenty patients had the
      duodenal segment sutured to the urinary bladder, and the remaining 31 grafts were
      drained to an isolated ileal loop. Quadruple immunosuppression was administered
      as well as an anticoagulant and antibiotic prophylaxis. Forty-nine patients
      (49/51, 96%) regained insulin independence in the immediate postoperative period;
      44 (86%) displayed immediate graft function. The remaining patients experienced
      postoperative ATN, the longest duration was 18 days. Of 51 patients, 38 (14.5%)
      are alive (follow-up, 6 to 180 months), 26 (68.5%) have good pancreatic function,
      and 34 (89%), good kidney function. Nineteen (50%) patients regard their quality
      of life as improved compared to their pretransplant status, which is mainly
      attributed to being dialysis and insulin free. Of 19 patients, 14 (74%) reported
      measuring glycemia regularly due to fear of losing the pancreas graft. Of 19
      persons, seven (37%) returned to work after transplantation. Four (8.3%) lost
      their kidney graft secondary to vascular complications (n = 2) or rejection (n =
      2). Four pancreas grafts with bladder drainage required conversion to enteric
      drainage owing to persistent urinary infections or urinary fistulae. Fifteen
      (29%) patients lost their pancreatic grafts within 1 year of transplantation due
      to the following: vascular complications (n = 12), septic complications (n = 1),
      or rejection (n = 2). Thirteen patients died within 1 year after transplantation,
      5 of septic complications, 5 of neuroinfection, 1 of pulmonary embolism, and 2 of
      myocardial infarction. In conclusion, SPKT is a successful treatment for diabetic
      nephropathy, burdened by the possibility of serious complications.

PMID- 16298660
TI  - Quality of life after simultaneous pancreas-kidney transplantation.
AB  - Even recipients with satisfactory function of transplanted pancreas and kidney
      may show physical and/or social disability due to diabetic complications. Our
      aims were to evaluate diabetic complications influencing recipient quality of
      life and to assess patients' psychosociological status. Nineteen patients with
      functioning grafts who consented to take part in the study, underwent clinical
      evaluation and answered questions regarding their quality of life. Results showed
      excellent endocrine pancreatic function in 17 patients. In most recipients,
      insulin activity and C-peptide levels were elevated owing to systemic venous
      drainage. Opthalmological examination revealed blindness in 7 patients (in 4
      cases with onset following SPKTx) and retinopathy in 13 patients (in 5 cases it
      appeared after SPKTx). Assessment of the cardiovascular system revealed
      satisfactory cardiac function in 16 of 19 patients; 4 patients underwent
      amputation of a lower limb following SPKTx. All 19 recipients admitted to a great
      benefit of transplantation; most patients declared ability to organize their life
      activity and social functions and 4 had regular employment. Conversely, most
      patients were afraid of graft loss, and half were often sad and even depressed.

PMID- 16298661
TI  - Infectious complications after simultaneous pancreas-kidney transplantation.
AB  - Simultaneous pancreas-kidney transplantation (SPKT) improves long-term survival
      of insulin-dependent diabetes mellitus patients with diabetic nephropathy. The
      increasing success of SPKT is a result of improved surgical technique, better
      organ preservation, potent antirejection therapy, and effective use of
      antibiotics to prevent and treat infectious complications. However, morbidity and
      mortality following SPKT remain high mainly owing to infection. From 1988 to
      2004, the 51 patients who underwent SPKT were 32 women and 19 men of mean age 34
      +/- 4 years old with diabetes and end-stage renal disease. The mean duration of
      diabetes mellitus was 23 +/- 4 years. The incidence of HCV and HBV infections
      were 19.6% and 13.7%, respectively. Preoperative work-up included identification
      and elimination prior to surgery of potential sources of infection. All patients
      prior to SPKTx had been treated by dialysis (26 +/- 20 months). The kidneys were
      always placed into the left retroperitoneal space first; at the same time the
      pancreatic grafts were prepared on the back table. The reconstruction of the
      superior mesenteric and the splenic arteries was performed using a Y graft of
      donor iliac artery to the common or external donor's iliac artery. The pancreas
      was transplanted intraperitoneally to the right iliac vessels. The portal vein
      was sutured to the common or external iliac vein and the arterial conduit of
      donor iliac artery. In 20 of the patients, bladder drainage and in 31, enteric
      drainage was used for the pancreatic juice exterioration. Patients received
      immunosuppression with a calcineurin inhibitor (tacrolimus or cyclosporin),
      mycophenolic acid or azathioprine, and steroids. Antibody induction
      (alternatively anti-IL-2 monoclonal antibody or ATG) was used in last 38
      patients. Antibacterial (tazobactam) and antifungal (fluconazole) as well as
      antiviral (gancyclovir) prophylactic treatment was given to all patients for 7 to
      10 days after transplantation. Thirty-eight recipients are alive, 26 with
      function of both grafts; 8 with functioning kidney grafts; and 4 with
      nonfunctioning grafts on dialysis treatment from 1 to 14 years after
      transplantation. Thirteen patients (24.5%) died during the first year after
      transplantation. Infectious complications were the main cause of death. Systemic
      infections accounted for the death of five patients and CNS infection for death
      of another five patients. Three patients died with functioning grafts due to
      cardiopulmonary disorders (myocardial infarction, pulmonary embolus) early in the
      postoperative period. A total of 102 infections were diagnosed in 51 patients
      during the posttransplant course. Twenty-one episodes of CMV infection (systemic
      20, duodenal site 1), 73 bacterial infections (systemic 13, pulmonary 13, urinary
      tract 15, intestinal 8, wound 23), and 8 fungal infections (central nervous
      system 5, gastrointestinal tract 3). Some patients had more than one type of
      infection. Overall mortality in the investigated group was 24.5%. Infectious
      complications were the main cause of death (77%), including systemic infection
      (38.5%) and CNS infection (38.5%). The predominant etiology of the systemic
      infections was bacterial. The etiology of CNS infections was fungal. In
      conclusion, infectious complications are the main cause of morbidity and
      mortality following SPKT. The early diagnosis of infection, particularly fungal
      complications, is necessary. The administration of broad-spectrum prophylactic
      antibiotics, antifungal, and antiviral agents is recommended.

PMID- 16298662
TI  - Obesity predicts increased overall complications following pancreas
      transplantation.
AB  - PURPOSE: We sought to evaluate the role of recipient body mass index (BMI) on
      postoperative complications in patients receiving pancreas transplants. METHODS:
      A single-institution retrospective study of 145 consecutive patients undergoing
      either simultaneous kidney pancreas (SPK) or pancreas after kidney (PAK)
      transplantation from January 1997 through December 2003. Variables analyzed
      included: age, sex, BMI, number of prior transplants, cytomegalovirus status of
      donor and recipient, postoperative insulin resistance, complications, and overall
      patient and graft survival. Differences in continuous variables and dichotomous
      variables were evaluated using two-tailed t test and Fisher exact test,
      respectively. Univariate and multivariate logistic regression analyses were
      employed to identify predictors of overall complications following surgery.
      RESULTS: Obesity was defined by a BMI > or = 30. Of the 145 patients, 33 (23%)
      had a BMI > or = 30 and 112 (77%) had a BMI < 30. There was no significant
      difference in age or sex between obese and nonobese patients (P = .98 and P =
      .56, respectively). The type of transplantation, SPK or PAK, did not affect the
      complication rate (P = .36). Overall complications (infection, dehiscence,
      evisceration, ventral hernia, allograft failure, gangrene, necrotizing fasciitis,
      postoperative bleeding, or death) were significantly higher in the obese group
      (81% vs 40%, P < .001). Obesity was specifically associated with increased
      frequency of dehiscence, ventral hernia, intra-abdominal infection, gangrene,
      necrotizing fasciitis, and repeat laparotomy. Obese patients also had a threefold
      higher rate of graft pancreatitis/enteric leak. Multivariate logistic regression
      analysis identified age > or = 50 and BMI > or = 30 as independent predictors of
      overall complications following surgery (odds ratio 4.0, P = .014 and OR 6.8, P <
      .001, respectively). There was no difference identified between groups with
      regards to allograft failure, posttransplant insulin resistance, and death.
      CONCLUSION: Obese patients are at increased risk of overall complications
      following pancreas transplantation. Specifically, obese patients experience
      higher frequency of dehiscence, ventral hernia, intra-abdominal infection,
      gangrene, and necrotizing fasciitis. This study demonstrates the need for careful
      postoperative monitoring in the obese patient.

PMID- 16298663
TI  - Simultaneous liver and pancreas transplantation in patients with cystic fibrosis.
AB  - BACKGROUND: Improved survival in patients with cystic fibrosis (CF) has led to an
      increased incidence of extrapulmonary complications of this disease. Of these,
      cirrhosis and pancreatic insufficiency, including CF-related diabetes (CFRD) and
      exocrine insufficiency, are significant causes of morbidity and mortality. Liver
      transplantation is the treatment of choice for cirrhosis in this setting, but the
      addition of an isolated simultaneous pancreas transplant in patients with CFRD
      has not been reported. METHODS: Two female patients with CF underwent
      simultaneous pancreas and liver transplantation. Both had pancreatic
      insufficiency, CFRD, cirrhosis, and preserved renal function. In each case, the
      liver and pancreas were procured from a single cadaveric donor. The liver
      transplant was performed first. A lower midline extension was added for improved
      exposure of the iliac vessels. The donor pancreas transplant was performed with
      systemic venous drainage and enteric exocrine drainage. Immunosuppression
      included rabbit anti-thymocyte globulin, tacrolimus, mycophenolate mofetil, and
      early steroid withdrawal. RESULTS: Both patients recovered well with normal liver
      function, resolution of portal hypertension, and normal blood glucoses
      independent of insulin. As a result of the enteric exocrine drainage of the
      pancreas, they are now independent of supplemental pancreatic enzymes.
      CONCLUSIONS: Simultaneous liver and pancreas transplantation in CF patients
      provides the advantages of normalization of glucose and improved nutrition for
      patients requiring liver transplantation and should be considered in CF patients
      with CFRD who require liver transplants.

PMID- 16298664
TI  - Cardiovascular benefits of simultaneous pancreas-kidney transplant versus kidney
      alone transplant in diabetic patients.
AB  - The aim of our study was to demonstrate the cardiovascular benefits of
      simultaneous pancreas-kidney transplantation when compared to kidney-alone
      transplants in diabetic recipients. PATIENTS AND METHODS: A total of 386 renal
      transplants were performed from 1985 to 2004, including 262 (68%) in diabetic
      recipients and 124 (32%) in nondiabetics. Among the former group, 200 kidneys
      were transplanted simultaneously to the pancreatic graft (KP group) and 62 were
      kidney-alone transplants (KA group). The mean time on dialysis was 31 +/- 20
      months (range 0-126 months). The duration of diabetes was 24 +/- 7 years (range 5
      51 years). Ninety-nine percent of the patients were on renal replacement therapy
      (79% on hemodialysis and 20% on peritoneal dialysis). RESULTS: Among 262
      patients, 28 (11%) died due to a cardiovascular event, which was higher among KA
      patients compared with the KP group (P = .004). Overall patient survival was
      significantly higher in the KP group when compared with the KA group (log-rank: P
      = .0004). Patient survivals were 80% and 70% versus 70% and 40% at 5 and 10 years
      in the KP and KA groups, respectively. Kidney graft survivals were 81% and 60%
      versus 63% and 26% at 5 and 10 years in the KP and KA groups, respectively.
      Pancreas graft survival was 70% and 50% at 5 and 10 years, respectively.
      CONCLUSIONS: This clinical evaluation, even if retrospective, confirmed that
      simultaneous pancreas-kidney transplantation has a protective effect against
      cardiovascular mortality in diabetic recipients affected by end-stage renal
      disease.

PMID- 16298665
TI  - Treatment of external iliac artery dissection with endovascular stent placement
      in a patient with simultaneous pancreas and kidney transplantation.
AB  - Dissection of the external iliac artery is a rare but serious complication after
      transplantation, leading to graft loss. Stent angioplasty has been accepted for
      iliac artery dissection, but the safety and benefits of this procedure in
      transplantation are unclear. We report a case of right external iliac artery
      dissection with simultaneous kidney and pancreas transplantation, which was
      noticed during the operation. A self-expandable metallic stent was inserted from
      the right femoral artery to the dissected area and arterial blood flow was
      immediately restored. The postoperative clinical course was uneventful and soon
      after transplantation both the kidney and pancreas graft functioned well.
      Together with a previously reported six cases of stent replacement with
      transplantation and our case, no complication related to this procedure was
      reported, and in six cases the arterial flow was restored and graft function was
      improved. Endovascular stent replacement may be a safe and effective procedure
      for iliac artery dissection in transplantation.

PMID- 16298666
TI  - Severe depletion of intraepidermal nerve fibers in skin biopsies of pancreas
      transplant recipients.
AB  - BACKGROUND: The minimally invasive method of skin biopsy with intraepidermal
      nerve fiber (IENF) counts may be used to analyze nerve regeneration in pancreas
      transplant (PTx) recipients. We assessed IENF counts as a database for long-term
      follow-up of diabetic neuropathy. METHODS: Skin biopsies were performed using a 3
      mm punch from lower thigh and upper calf areas of 16 (13 pancreas/kidney, 3
      pancreas alone) PTx patients (mean +/- SD: age, 45+/-8 years; type 1 diabetes
      duration, 27 +/- 8 years) at 1 month posttransplant. Ten healthy gender- and age
      matched controls (C) were also examined. After fixation and freezing, 40-microm
      sections were stained using rabbit polyclonal antibody to the panaxonal marker
      PGP 9.5 followed by mouse antirabbit IgG antibody conjugated with rhodamine.
      Samples were imaged with a digital camera, mounted on a microscope, and equipped
      for fluorescence. The average number of IENF per millimeter length of epidermis
      was derived. Clinical neuropathy was assessed by foot vibration perception
      thresholds (VPT) with a biothesiometer (normal values < mean + 2 SD of C).
      RESULTS: Significantly lower IENF densities were found in skin biopsies from PTx
      (PTx vs C: thigh, 0.74 +/- 0.88 vs 9.74 +/- 2.41 IENF/mm; calf, 0.34 +/- 0.91 vs
      7.66 +/- 3.16 IENF/mm; P < .001). IENF were totally absent from the thigh and
      calf samples of 7 and 12 PTxs, respectively. Clinical neuropathy (VPT > 21 V) was
      present in all but one PTx. CONCLUSIONS: Severe intraepidermal nerve fiber
      depletion is present in the lower limb area of pancreas transplant recipients
      with neuropathy. Long-term follow-up would probably be necessary to assess the
      possibility of posttransplant nerve fiber regeneration.

PMID- 16298667
TI  - Processing homonymy and polysemy: effects of sentential context and time-course
      following unilateral brain damage.
AB  - The present study investigated the abilities of left-hemisphere-damaged (LHD) non
      fluent aphasic, right-hemisphere-damaged (RHD), and normal control individuals to
      access, in sentential biasing contexts, the multiple meanings of three types of
      ambiguous words, namely homonyms (e.g., "punch"), metonymies (e.g., "rabbit"),
      and metaphors (e.g., "star"). Furthermore, the predictions of the "suppression
      deficit" and "coarse semantic coding" hypotheses, which have been proposed to
      account for RH language function/dysfunction, were tested. Using an auditory
      semantic priming paradigm, ambiguous words were incorporated in dominant- or
      subordinate-biasing sentence-primes followed after a short (100 ms) or long
      (1,000 ms) interstimulus interval (ISI) by dominant-meaning-related, subordinate
      meaning-related or unrelated target words. For all three types of ambiguous
      words, both the effects of context and ISI were obvious in the performance of
      normal control subjects, who showed multiple meaning activation at the short ISI,
      but eventually, at the long ISI, contextually appropriate meaning selection.
      Largely similar performance was exhibited by the LHD non-fluent aphasic patients
      as well. In contrast, RHD patients showed limited effects of context, and no
      effects of the time-course of processing. In addition, although homonymous and
      metonymous words showed similar patterns of activation (i.e., both meanings were
      activated at both ISIs), RHD patients had difficulties activating the subordinate
      meanings of metaphors, suggesting a selective problem with figurative meanings.
      Although the present findings do not provide strong support for either the
      "coarse semantic coding" or the "suppression deficit" hypotheses, they are viewed
      as being more consistent with the latter, according to which RH damage leads to
      deficits suppressing alternative meanings of ambiguous words that become
      incompatible with the context.

PMID- 16298668
TI  - The propositional structure of discourse in the two cerebral hemispheres.
AB  - Readers construct at least two interrelated representations when they comprehend
      a text: (a) a representation of the explicit ideas in a text and the relations
      among them (i.e., a propositional representation) and (b) a representation of the
      context or situation to which a text refers (i.e., a discourse model). In a
      recent study, found evidence that readers' representations were structured
      according to propositional relations, but only in the left hemisphere. Both
      hemispheres, however, appeared to represent contextually relevant semantic
      information. The goal in the current study was to examine further the
      organization of explicit text concepts in the two hemispheres. We used an item
      priming-in-recognition paradigm in combination with a lateralized visual-field
      manipulation. We found evidence for a propositionally structured representation
      in the left hemisphere, that is, priming effects that reflected the linear
      distance between primes and targets in the propositional structure of passages.
      We also found that the right hemisphere represented explicit text concepts, but
      we found no evidence that these concepts were organized structurally. In a second
      experiment, we found our item priming effects reflected the representation of
      text information in memory and did not reflect lexical-semantic priming at test.

PMID- 16298669
TI  - Double-decision lexical tasks in thought-disordered schizophrenic patients: a
      path towards cognitive remediation?
AB  - It has been shown that schizophrenics have certain difficulties in the processing
      of semantic context. These difficulties have usually been evaluated using lexical
      decision tasks with semantic priming. In this study, we chose to examine the idea
      of an abnormality in the early stages of semantic context processing in thought
      disordered schizophrenics using two double lexical decision tasks: one with a
      high (25%) and one with a low (15%) proportion of related words to assess the
      participants' competency in controlled and possibly also more automatic context
      processing. The results obtained in 40 control participants and 40 schizophrenic
      patients revealed no significant differences in the amplitude of semantic priming
      between the two groups. These results suggest that, in the disorganized
      schizophrenic subjects evaluated in this study, the context processing processes
      mobilized by the employed tasks were unimpaired.

PMID- 16298670
TI  - Evidence for dissociable neural mechanisms underlying inference generation in
      familiar and less-familiar scenarios.
AB  - In this study, we investigated whether the left and right hemispheres are
      differentially involved in causal inference generation. Participants read short
      inference-promoting texts that described either familiar or less-familiar
      scenarios. After each text, they performed a lexical decision on a letter string
      (which sometimes constituted an inference-related word) presented directly to the
      left or right hemisphere. Response-time results indicated that hemisphere of
      direct presentation interacted with type of inference scenario. When test stimuli
      were presented directly to the left hemisphere, lexical decisions were
      facilitated following familiar but not following less-familiar inference
      scenarios, whereas when test stimuli were presented directly to the right
      hemisphere, facilitation was observed in both familiar and less-familiar
      conditions. Thus, inferences may be generated in different ways depending on
      which of two dissociable neural subsystems underlies the activation of background
      information.

PMID- 16298671
TI  - Auditory backward masking deficits in children with reading disabilities.
AB  - Studies evaluating temporal auditory processing among individuals with reading
      and other language deficits have yielded inconsistent findings due to
      methodological problems () and sample differences. In the current study, seven
      auditory masking thresholds were measured in fifty-two 7- to 10-year-old children
      (26 diagnosed with reading disability [RD], 26 without reading disability).
      Hierarchic multiple regression analyses indicated that RD status predicted
      performance only in the backward-bandpass noise (p<.05) and backward notched
      noise conditions (p<.05), suggesting both temporal and spectral auditory
      processing deficits. These results suggest that any auditory deficit associated
      with RD may be more complex than previously hypothesized.

PMID- 16298672
TI  - Interesting case: Wegener's granulomatosis--a cause of eyelid swelling.

PMID- 16298673
TI  - Interesting case: kissing molars.

PMID- 16298674
TI  - Variants, pitfalls and asymptomatic findings in wrist and hand imaging.
AB  - Anatomic variants of the bones, ligaments, tendons and muscles are frequent
      findings in imaging of the wrist and hand. Many findings especially changes in
      the triangular fibrocartilage (TFC) and the interosseous ligaments are
      asymptomatic, their incidence is increasing with age, and they are frequently
      found bilaterally. Abnormalities such as increased signal within tendons are
      common in asymptomatic subjects. They may be explained by normal physiology,
      anatomical variability, MR artifacts or true abnormalities without clinical
      importance. Although it is not always possible to differentiate variants and
      artifacts from clinically relevant findings it is important to know their
      potential etiology and clinical importance and not to over report them as
      abnormality requiring additional imaging or treatment.

PMID- 16298676
TI  - Synovial inflammatory processes in the hand.
AB  - The numerous synovial articulations and tendon sheaths of the hand afford it a
      central role in the diagnosis and management of inflammatory arthropathies.
      Inflammation may be idiopathic, infectious, post-traumatic, or secondary to
      deposition diseases. In most cases, synovial inflammation represents the primal
      event in the onset of destructive arthropathies. We review the imaging features
      of acute and chronic synovitis in the hand. Magnetic resonance imaging is very
      sensitive to the earliest changes of synovitis and provides a modality for early
      detection of disease. Additionally, once a diagnosis is established, magnetic
      resonance imaging has an emerging role in rapid assessment of response to
      therapy. Positron emission tomography and ultrasound also show promise in the
      evaluation and treatment of inflammatory arthropathies. Although highly sensitive
      to the presence of inflammation these more advanced imaging techniques often lack
      specificity. Therefore, the radiographic evaluation of the pattern of bone
      destruction remains critical to distinguishing among the different synovial
      inflammatory processes.

PMID- 16298675
TI  - MR imaging of the finger tendons: normal anatomy and commonly encountered
      pathology.
AB  - MR imaging has emerged as a powerful tool in the evaluation of soft tissue
      structures such as the tendons of the hand and finger due to its excellent soft
      tissue contrast and multiplanar imaging capabilities. In the finger and hand,
      perhaps more than in any other location in the body, a detailed and intimate
      understanding of anatomy is crucial for lesion localization, directing clinical
      management and predicting long-term prognosis. These issues are of paramount
      importance to both the clinician and imager, both faced with the challenge of the
      complex anatomy and pathology associated with these delicate structures. The
      anatomy of the finger including intrinsic and extrinsic muscles, retinacular
      structures, and tendons will be discussed. The MR imaging features of common
      lesions of the tendons of the hand and finger will be reviewed.

PMID- 16298677
TI  - Vascular lesions of the hand.
AB  - The vascular malformations are not uncommon on the hand and offer diagnostic and
      therapeutic challenges. Enjolras and Mulliken's classification is exposed. Their
      depiction and pretreatment assessment may benefit from non-invasive imaging as
      color-Doppler ultrasound and MRI combined with magnetic resonance angiography
      (MRA). Some chronic traumatic vascular injuries as the hypothenar hammer syndrome
      may also take advantage of these imaging modalities.

PMID- 16298678
TI  - Efficacy and complications of Angioseal in antegrade puncture.
AB  - AIM: Although arterial closure devices are in use for over a decade, there have
      been no specific study to assess the use of the same in antegrade puncture.
      MATERIAL AND METHOD: Consecutive patients undergoing antegrade puncture for
      peripheral vascular disease in a single centre performed by a single operator
      were included in this study. The notes and the angiograms were reviewed
      retrospectively for possible complications and the severity of disease. RESULT:
      Over a 25-month period, 21 patients with antegrade puncture had Angioseal
      deployed for haemostasis. Post-procedure complications recorded from the case
      notes showed one episode of haematoma formation and one case of worsening
      ischaemia. The severity of the disease at the puncture site did not influence the
      outcome. CONCLUSION: Use of Angioseal is safe and effective in antegrade
      punctures for peripheral vascular disease. The result is independent of the
      severity of disease at the puncture site.

PMID- 16298679
TI  - n-Alkyl glucopyranosides completely inhibit ultrasound-induced cytolysis.
AB  - The mechanism(s) responsible for sudden cytolysis observed when cells are exposed
      to ultrasound could be mechanical and/or free radical in nature. Free radical
      reactions are initiated in the core and in the interfacial regions of collapsing
      acoustic cavitation bubbles. Because cyclic sugars are known to inhibit free
      radical chain reactions, we investigated the effects of n-alkyl-beta-d
      glucopyranosides of varying hydrophobicity on ultrasound (1.057 MHz)-induced
      cytolysis of HL-60 cells in vitro. n-Alkyl glucopyranosides with hexyl- (5 mM),
      heptyl- (3 mM), or octyl- (2 mM) n-alkyl chains protected 100% of the cell
      population from ultrasound-induced cytolysis under a range of conditions that
      resulted in 35 to 100% cytolysis in the absence of glucopyranosides. The
      protected cell populations also possessed long-term reproductive viability.
      However, the hydrophilic methyl-beta-D-glucopyranoside could not protect cells,
      even up to a concentration of 30 mM. Furthermore, none of the glucopyranosides
      could prevent cytolysis of cells from a mechanically induced shear stress. Spin
      trapping and electron spin resonance experiments confirmed the presence of
      inertial cavitation in cell suspensions both in the presence and in the absence
      of the surfactants. It is concluded that surface-active glucopyranosides
      efficiently quench cytotoxic radicals and/or their precursors at the gas/solution
      interface of collapsing cavitation bubbles.

PMID- 16298680
TI  - Thioredoxin-1 suppresses lung injury and apoptosis induced by diesel exhaust
      particles (DEP) by scavenging reactive oxygen species and by inhibiting DEP
      induced downregulation of Akt.
AB  - Diesel exhaust particles (DEP) are reactive oxygen species (ROS)-inducing toxic
      agents that damage lungs. Thioredoxin-1 (Trx-1) is a thiol protein with
      antioxidant and redox-regulating effects. In this study, we demonstrate that Trx
      1 scavenges ROS generated by DEP and attenuates the lung injury. Intratracheal
      instillation of DEP resulted in the generation of more hydroxyl radicals in
      control mice than in human Trx-1 (hTrx-1)-transgenic mice as measured by
      noninvasive L-band in vivo electron spin resonance. DEP caused acute lung damage
      with massive infiltration of inflammatory cells in control mice, but much less
      damage in hTrx-1-transgenic mice. The hTrx-1 transgene protected the mice against
      DEP toxicity. To investigate further the molecular mechanism of the protective
      role of Trx-1 against DEP-induced lung injury, we used hTrx-1-transfected L-929
      cells and recombinant hTrx-1 (rhTrx-1)-pretreated A-549 cells. DEP-induced ROS
      generation was suppressed by hTrx-1 transfection or pretreatment with rhTrx-1.
      Endogenous Trx-1 expression was induced by DEP in control cells. The
      downregulation of Akt phosphorylation by DEP resulted in apoptosis, which was
      prevented by Trx-1. Moreover, an Akt inhibitor canceled this protective effect of
      Trx-1. Collectively, the results suggest that Trx-1 exerts antioxidant effects in
      vivo and in vitro and that this plays a role in protection against DEP-induced
      lung damage by regulating Akt-mediated antiapoptotic signaling.

PMID- 16298681
TI  - Immunomodulatory cytokines suppress epithelial nitric oxide production in
      inflammatory bowel disease by acting on mononuclear cells.
AB  - Inducible nitric oxide synthase (iNOS) activity in colonic epithelial HT-29 cells
      is modulated by the T-cell-derived cytokines IL-4 and IL-13, but is not affected
      by IL-10 despite its effect in models of colitis. We studied the effects of these
      cytokines on nitric oxide (NO) production by colonic tissue. IL-10 and IL-4 but
      not IL-13 suppressed the NO production and iNOS expression by inflamed tissue and
      cytokine-stimulated noninflamed tissue from patients with ulcerative colitis,
      whereas the three cytokines suppressed NO production in cytokine-stimulated
      biopsies from controls. To examine why colonic biopsies and HT-29 cells respond
      differently to immunomodulatory cytokines, a coculture of mixed mononuclear
      monocytes (MMC) and HT-29 cells was studied. Treatment of HT-29 cells with
      conditioned medium from IFN-gamma/LPS-stimulated MMC produced significant amounts
      of NO, which suggested the presence of an MMC-derived soluble factor modifying
      epithelial NO production. Pretreatment of IFN-gamma/LPS-stimulated MMC with IL-10
      and IL-4 but not IL-13 suppressed NO production by HT-29 cells. Interestingly,
      pretreatment of HT-29 cells with IL-1 receptor antagonist suppressed the IFN
      gamma/LPS-stimulated MMC-induced NO production. These results suggest that
      immunomodulatory cytokines might exert an inhibitory effect on NO up-regulation
      by colonic epithelium via the inhibition of MMC-derived soluble mediators, such
      as IL-1.

PMID- 16298682
TI  - Attenuation of cardiac hypertrophy by inhibiting both mTOR and NFkappaB
      activation in vivo.
AB  - A role for the PI3K/Akt/mTOR pathway in cardiac hypertrophy has been well
      documented. We reported that NFkappaB activation is needed for cardiac
      hypertrophy in vivo. To investigate whether both NFkappaB activation and
      PI3K/Akt/mTOR signaling participate in the development of cardiac hypertrophy,
      two models of cardiac hypertrophy, namely, induction in caAkt-transgenic mice and
      by aortic banding in mice, were employed. Rapamycin (2 mg/kg/daily), an inhibitor
      of the mammalian target of rapamycin, and the antioxidant pyrrolidine
      dithiocarbamate (PDTC; 120 mg/kg/daily), which can inhibit NFkappaB activation,
      were administered to caAkt mice at 8 weeks of age for 2 weeks. Both rapamycin and
      PDTC were also administered to the mice immediately after aortic banding for 2
      weeks. Administration of either rapamycin or PDTC separately or together to caAkt
      mice reduced the ratio of heart weight/body weight by 21.54, 32.68, and 42.07%
      compared with untreated caAkt mice. PDTC administration significantly reduced
      cardiac NFkappaB activation by 46.67% and rapamycin significantly decreased the
      levels of p70S6K by 34.20% compared with untreated caAkt mice. Similar results
      were observed in aortic-banding-induced cardiac hypertrophy in mice. Our results
      suggest that both NFkappaB activation and the PI3K/Akt signaling pathway
      participate in the development of cardiac hypertrophy in vivo.

PMID- 16298683
TI  - Redox cycling of iron complexes of N-(dithiocarboxy)sarcosine and N-methyl-D
      glucamine dithiocarbamate.
AB  - Iron(II)-dithiocarbamate complexes are used to trap nitrogen monoxide in
      biological samples, and the resulting nitrosyliron(II)-dithiocarbamate is
      detected and quantified by ESR. As the chemical properties of these compounds
      have been little studied, we investigated whether iron dithiocarbamate complexes
      can redox cycle. The electrode potentials of iron complexes of N
      (dithiocarboxy)sarcosine (dtcs) and N-methyl-d-glucamine dithiocarbamate (mgd)
      are 56 and -25 mV at pH 7.4, respectively, as measured by cyclic voltammetry. The
      autoxidation and Fenton reaction of iron(II)-dtcs and iron(II)-mgd were studied
      by stopped-flow spectrophotometry with both iron(II) complexes and dioxygen or
      hydrogen peroxide in excess. In the case of excess iron(II)-dtcs and -mgd
      complexes, the rate constants of the autoxidation and the Fenton reaction are
      (1.6-3.2) x 10(4) and (0.7-1.1) x 10(5) M(-1) s(-1), respectively. In the
      presence of nitrogen monoxide, the oxidation of iron(II)-dtcs and iron(II)-mgd by
      hydrogen peroxide is significantly slower (ca. 10-15 M(-1) s(-1)). The
      physiological reductants ascorbate, cysteine, and glutathione efficiently reduce
      iron(III)-dtcs and iron(III)-mgd. Therefore, iron bound to dtcs and mgd can redox
      cycle between iron(II) and iron(III). The ligands dtcs and mgd are slowly
      oxidized by hydrogen peroxide with rate constants of 5.0 and 3.8 M(-1) s(-1),
      respectively.

PMID- 16298684
TI  - Protection against nuclear DNA damage offered by flavonoids in cells exposed to
      hydrogen peroxide: the role of iron chelation.
AB  - The ability of a number of flavonoids belonging to the flavone, flavonol,
      flavanone, and flavan-3-ol subclasses to protect cellular DNA from H2O2-induced
      single-strand breaks and the underlying molecular mechanisms were investigated in
      this work. Formation of single-strand breaks on nuclear DNA, after exposure of
      Jurkat cells to continuously generated H2O2 in the presence or absence of the
      flavonoid compounds, was evaluated by the comet assay (single-cell gel
      electrophoresis). The results indicate the following structural requirements of
      flavonoids for effective DNA protection: (a) the ortho-dihydroxy structure in
      either ring A or ring B, (b) the hydroxyl moiety on position 3 in combination
      with the oxo group at position 4, and (c) the presence of a C2, C3 double bond in
      ring C. In contrast to free flavonoids, the ability of complexes of
      [Fe2+]/[flavonoid] to protect nuclear DNA was decreased as the ratio increased,
      and the complex was completely inactive when the ratio reached a certain value.
      Moreover, it was observed that several of the flavonoids tested were able to
      remove iron from calcein loaded into cells and that this property was in
      excellent correlation with their ability to protect DNA (Spearman's correlation
      coefficient, rho = 0.9, p = 0.005). The antioxidant (electron donating)
      capacities of the same flavonoids were also evaluated by a conventional method,
      but no relation with their DNA-protective ability could be established even when
      their membrane-penetrating abilities were taken into account (p = 0.64). In
      conclusion, the results presented in this work strongly support the notion that
      intracellular binding of iron is responsible for the protection offered by
      flavonoids against H2O2-induced DNA damage.

PMID- 16298685
TI  - Activation of AP-1 through reactive oxygen species by angiotensin II in rat
      cardiomyocytes.
AB  - Cardiovascular pathogenesis induced by angiotensin II (Ang-II) is a complex
      process often connected to oxidative stress. In the present study we show that, 4
      h after addition, Ang-II induces a four- to fivefold increase in AP-1 activity in
      cultured neonatal rat cardiomyocytes and that the intracellular level of reactive
      oxygen species (ROS) correlates with the extent of AP-1 binding activity. Ang-II
      stimulated ROS generation in rat cardiomyocytes in a dose- and time-dependent
      manner. These effects of Ang-II were suppressed by the Ang-II receptor type I
      (AT1) inhibitor CV-11974 as well as by the antioxidants diphenylene iodonium
      (DPI) and N-acetyl-L-cysteine (NAC), but not by AT2 antagonist PD 122319.
      Furthermore, Ang-II induced a two- to threefold increase in protein synthesis and
      cell size during 12-24 h, which could be inhibited by CV-11974 as well as by DPI
      and NAC. Because the rat cardiomyocytes strongly expressed gp91(phox), this
      suggests that ROS generated in a gp91-containing NADPH oxidase are involved in
      signal transduction leading to AP-1 activation. Together, these findings indicate
      that Ang-II elicits the activation of the redox-sensitive AP-1 via ROS through
      AT1, resulting in effects on cardiomyocyte function such as hypertrophy.

PMID- 16298686
TI  - GDNF modulates HO-1 expression in substantia nigra postnatal cell cultures.
AB  - Heme oxygenase-1 (HO-1) has been strongly highlighted because of its induction in
      many cell types by toxic stimuli, including oxidative stress. The intense HO-1
      immunostaining in the substantia nigra of Parkinson disease (PD) patients
      suggests its involvement in the pathogenesis of this neurodegenerative disease.
      In this work we investigated HO-1 expression in rat substantia nigra postnatal
      cell cultures under conditions mimicking dopamine toxicity and its modulation by
      glial cell line-derived neurotrophic factor (GDNF), a potent neuroprotective
      factor for dopaminergic neurons. In neuron-glia cultures, we found that H2O2, a
      product of dopamine metabolism, or l-3,4-dihydroxyphenylalanine (L-DOPA), the
      dopamine precursor used in the therapy of PD, induced a fast up-regulation of HO
      1 mRNA and protein levels, followed by a secondary down-regulation. H2O2 and L
      DOPA also increased HO-1 expression in astrocyte cultures, but with a delayed
      time course in H2O2-treated cultures. HO-1 expression was decreased in neuron
      glia cultures under conditions under which GDNF up-regulation was observed.
      Because exogenously applied GDNF prevented HO-1 up-regulation in cultures treated
      with H2O2 or l-DOPA, and antibody neutralization of GDNF prevented the secondary
      HO-1 down-regulation observed in neuron-glia cultures, we propose that GDNF
      negatively modulates HO-1 expression induced by oxidative stress. To our
      knowledge, this is the first report showing the modulation of HO-1 expression by
      GDNF.

PMID- 16298687
TI  - Pro-oxidant effects of extremely low frequency electromagnetic fields in the land
      snail Helix aspersa.
AB  - Pro-oxidant effects of extremely low frequency (ELF) 50-Hz magnetic fields were
      investigated in the land snail Helix aspersa exposed both in short-term
      laboratory treatments and under field conditions by maintaining the organisms in
      the proximity of a power line for up to 2 months. Oxidative perturbations were
      investigated as individual antioxidants (catalase, glutathione reductase,
      glutathione S-transferases, and total glutathione) and total scavenging capacity
      toward peroxyl radicals and hydroxyl radicals. Accumulation of lipid peroxidation
      products, destabilization of lysosomal membranes, and loss of DNA integrity were
      also evaluated as markers of cell damage. The overall results indicated an
      oxidative challenge caused by ELF magnetic fields with particularly prompt and
      sensitive responses for catalase, glutathione reductase, and the overall
      capability to neutralize peroxyl radicals. Cell injuries occurred to different
      extents according to duration and intensity of electromagnetic exposure and
      confirmed complex cause-effect relationships between pro-oxidant factors,
      efficiency of antioxidant defenses, and the onset of oxidative toxicity. This
      study highlights the importance of a multimarker approach for detecting a wide
      panel of biological responses, the necessity of investigating the long-term
      effects of early oxidative responses, and the role of ELF in enhancing
      susceptibility to other forms of pathologies or diseases.

PMID- 16298688
TI  - Low UVA doses activate the transcription factor NFAT in human fibroblasts by a
      calcium-calcineurin pathway.
AB  - UVA radiation induces an inflammatory response as observed in erythema, and the
      cytokine genes involved in this response are under the control of the
      transcription factor NFAT (nuclear factor of activated T lymphocytes). The
      effects of UVA on NFAT DNA binding activity were investigated in cultured human
      fibroblasts. A dose-dependent increase was observed within the range of 0.6-4.5
      J/cm2 UVA. Beyond this value, the activity decreased and a value of 60% of
      control was found at 13.5 J/cm2. The enhancement of NFAT activity was transient
      and peaked 45 min after irradiation. Furthermore, immunoblot analysis
      demonstrated a nuclear translocation of NFAT under low UVA doses. Concomitantly,
      as assessed by the fluorescent probe Fluo3, UVA induced an increase in
      intracellular free calcium, with a maximum increase found at 9 J/cm2. The UVA
      induced activation of NFAT was prevented by the intracellular calcium trapping
      drug BAPTA, whereas the extracellular calcium chelator EGTA had no significant
      effect. In addition, the calcineurin inhibitors cyclosporin A and FK506 both
      prevented the UVA-induced NFAT activation. Furthermore, the antioxidant vitamin E
      prevented the UVA-induced increase in both intracellular free calcium and NFAT
      binding activity. Finally, the cytotoxicity of UVA was enhanced in the presence
      of the inhibitors cyclosporin and FK506, suggesting that the activation of NFAT
      might play a protective role after the UVA-induced oxidative stress. These
      results demonstrate that UVA activates the calcium-calcineurin signaling pathway
      of NFAT activation, that the calcium ions are mainly released from intracellular
      stores, and that the increase in calcium is, at least partially, due to the
      oxidative stress generated under UVA. Because NFAT regulates several genes
      implicated in the inflammatory response, the enhancement of NFAT activity by low
      UVA doses might be interpreted in view of the proinflammatory action of solar
      radiation.

PMID- 16298689
TI  - Role of Bcl-2 in the arachidonate-mediated survival signaling preventing
      mitochondrial permeability transition-dependent U937 cell necrosis induced by
      peroxynitrite.
AB  - Antisense technology was successfully employed to selectively reduce the
      expression of Bcl-2 in U937 cells, while leaving their redox status intact. These
      cells displayed enhanced sensitivity to mitochondrial permeability transition
      (MPT)-dependent apoptosis induced by arsenite and underwent a rapid, MPT
      dependent necrotic response after exposure to otherwise nontoxic concentrations
      of peroxynitrite. Several lines of evidence consistently indicate that these low
      concentrations of peroxynitrite nevertheless commit cells to MPT, which is,
      however, prevented by a survival signaling in which arachidonic acid, protein
      kinase Calpha (PKCalpha), and Bcl-2 are sequentially involved. Bcl-2, however,
      was not the direct target of PKCalpha but most likely Bad, a protein involved in
      the regulation of Bcl-2 activity via heterodimerization. Further studies revealed
      that Bcl-2 does not afford protection in cells challenged with intrinsically
      toxic concentrations of peroxynitrite. This was due to depletion of GSH, an event
      leading to loss of the anti-MPT function of Bcl-2. Collectively, these results
      demonstrate a role of Bcl-2 in monocyte survival signaling preventing MPT
      dependent necrosis induced by peroxynitrite, and provide an explanation for the
      reported observation that Bcl-2 fails to prevent necrosis mediated by
      intrinsically toxic levels of peroxynitrite.

PMID- 16298690
TI  - Modulation of DNA-dependent protein kinase activity in chlorambucil-treated
      cells.
AB  - DNA-dependent protein kinase (DNA-PK) is activated in a two-step process whereby
      the Ku heterodimer first binds to the DNA double-strand breaks (dsbs) and then
      the DNA-PK catalytic subunit (cs) is recruited to form a repair complex.
      Oxidative stress is simultaneously generated along with DNA damage by ionizing
      radiation or chemotherapeutic agents whose impact on the DNA-PK activity has not
      previously been investigated. Here we show that the DNA damage-induced kinase
      activity of DNA-PK was modulated by oxidative stress, which was induced along
      with DNA dsbs in chlorambucil (Cbl)-exposed cells. Pretreatment with the
      antioxidants, 2(3)-t-butyl-4-hydroxyanisole or N-acetyl-l-cysteine enhanced the
      amount of DNA-PKcs phosphorylated at threonine 2609 (DNA-PK(pThr2609)) at the DNA
      dsbs and DNA-PK activity. Conversely, oxidative stress induced by l-buthionine
      (SR)-sulfoximine or glucose oxidase decreased the DNA-PK activity in Cbl-exposed
      cells. In addition, DNA-PK(pThr2609) was poorly detectable at the site of DNA
      dsbs, as shown by colocalization to DNA-end-binding pH2AX or p53BP1. There was no
      change in the protein levels of DNA-PKcs, Ku70, or Ku86. Data from these studies
      provide the first evidence that oxidative stress effects posttranslational
      modification and assembly of DNA-PK complex at DNA dsbs, and thereby repair of
      DNA dsbs.

PMID- 16298691
TI  - Autoantibodies against oxidized LDL are associated with severe chest pain attacks
      in patients with coronary heart disease.
AB  - Autoantibodies against oxidized low-density lipoprotein (oxLDL) predict the
      progression of atherosclerosis. Several studies have shown that oxLDL is present
      in atherosclerotic lesions and that several factors present in active
      atherosclerotic plaques can oxidatively modify LDL. Oxidation of LDL induces
      production of autoantibodies against oxLDL (oxLDLab) that can be measured using
      an EIA test. Our aim was to see whether oxLDLab are associated with severe chest
      pain attacks in coronary heart disease (CHD) patients. Patients having two- or
      three-vessel CHD, as assessed by coronary angiography, and their siblings were
      recruited into the study (n = 568, mean age 55.8 years, range 29.3-83.2 years).
      Nondiabetic patients having a history of severe chest pain attacks had
      significantly higher oxLDLab levels (0.611 +/- 0.56) than those who did not have
      a history of severe chest pain attacks (0.487 +/- 0.40) (p = 0.027), even though
      age, cholesterol level, body mass index, and blood pressure were similar in both
      groups. However, no difference was found in oxLDLab levels in diabetic patients
      with or without a history of severe chest pain attacks. Increased levels of oxLDL
      autoantibodies are associated with severe chest pain attacks in nondiabetic
      patients with CHD.

PMID- 16298693
TI  - Peer review: sacred cow or scientific necessity?

PMID- 16298692
TI  - Induction of apoptosis by the overexpression of an alternative splicing variant
      of mitochondrial thioredoxin reductase.
AB  - Mammalian cells harbor two forms of thioredoxin reductase (TrxR), cytosolic TrxR1
      and mitochondrial TrxR2, both of which are involved in the redox regulation of
      cell growth and apoptosis. Furthermore, several alternative splicing variants of
      TrxR1 and TrxR2 have been identified. However, little remains known with regard
      to their functions in cells. Here, we report an alternative splicing variant of
      TrxR2 (TrxR2A), which displays a 3-bp deletion in the coding region and an
      insertion of 1228 bp in the 3'-UTR, between the stop codon and the SECIS element,
      of the TrxR2 cDNA. In order to determine the cellular function of TrxR2A, we
      established TrxR2A-inducible HeLa cell lines in which TrxR2A transcription was
      regulated via a Tet-off expression system. We observed that the induction of
      TrxR2A resulted in increased apoptosis, due to the reduction of NADPH and
      alterations in cellular ROS levels. These results suggest that TrxR2A may play a
      vital role in the regulation of TrxR2 and may confer functional complexity onto
      the thioredoxin system.

PMID- 16298694
TI  - Nurses' beliefs about family presence during resuscitation.
AB  - The purpose of this descriptive qualitative study was to explore the beliefs and
      experiences of RNs about family presence (FP) during cardiopulmonary
      resuscitation. Ten RNs with a minimum of 4 years of clinical experience working
      in diverse acute care units provided data for the study. Data were analyzed using
      the constant comparative method. Four themes emerged: (a) the conditions under
      which FP is an option; (b) using FP to force decision making; (c) staff's
      feelings of "being watched"; and (d) the impact of FP on a family. Because FP is
      not traditionally practiced, it may not be a consideration unless brought to the
      attention of administration by nursing staff committed to changing their policy.

PMID- 16298695
TI  - Individualizing memory strategies to improve medication adherence.
AB  - Changes in cognitive processes are well documented among even essentially healthy
      community-dwelling older adults. Although these changes do not produce the level
      of cognitive impairment associated with dementia, they do have the capacity to
      influence the degree to which elderly individuals self-manage chronic conditions.
      This pilot investigation tested the effect of an intervention to improve
      remembering to take medications and tracking if medications were taken as
      intended. Twenty-seven older adults (age range = 67-89 years, M = 78 years) all
      self-managing prescribed medications had one medication electronically monitored
      for 8 weeks preintervention and then 8 weeks postintervention. The percentage of
      days the correct number of doses was taken increased from a mean of 64.5% to that
      of 78%. With the use of Wilcoxon's signed ranks test, this improvement in
      adherence is significant. When participants with dementia or mild cognitive
      impairment were eliminated from the analysis (n = 6), the intervention continued
      to improve adherence (70.6% to 86%), suggesting that many older adults have the
      potential to improve adherence through individualized implementation of memory
      strategies.

PMID- 16298696
TI  - A psychoeducational program for nursing staff managing problematic behaviors of
      elderly nursing home residents in Taiwan.
AB  - This quasi-experimental study assessed the influence of a psychoeducational train
      ing program on the knowledge, attitudes, and self-efficacy of nursing home staff
      (nursing aides [NAs] and registered nurses [RNs]) regarding elderly residents and
      the management of their problematic behaviors. The training, which was conducted
      in northern Taiwan, was based on self-directed learning theory. Participants were
      divided into experimental (n = 130) and control (n = 140) groups. Staff's
      knowledge, attitudes, and self-efficacy were assessed before, immediately after,
      and 3 months after the program. Total knowledge improved significantly in all
      participants. For RNs, attitudes toward residents with disruptive behaviors and
      self-efficacy in managing these behaviors also improved, but these improvements
      were not maintained. These findings indicate that cognition is not the only
      factor influencing attitudes and self-efficacy.

PMID- 16298697
TI  - Symptom-focused management for African American women with Type 2 diabetes: a
      pilot study.
AB  - The purpose of this pilot study was to test the effectiveness of an in-home,
      nurse-delivered, symptom-focused teaching/counseling intervention with older
      rural African American women who have type 2 diabetes. Forty-one participants
      were randomly assigned to either the intervention or the comparison group.
      Participants in the intervention showed statistically significant improvement in
      their medication, diet, home glucose monitoring self-care practices, perceptions
      of quality of life, and distress from symptoms. Both groups evidenced improvement
      of HbA(1c) levels. The intervention group achieved greater improvement, but the
      difference was not statistically significant. Participant satisfaction was high.
      Further studies should look into the cost of the intervention, as compared with
      that of usual care, and its long-term effects.

PMID- 16298698
TI  - Home health care nursing research priorities.
AB  - The purpose of this study was to determine research priorities for home health
      care nursing. A Delphi study was undertaken to generate and prioritize research
      topics. The first round consisted of members of the Home Health Nurses
      Association Research Committee (n = 27); subsequent rounds also included nurse
      researchers who had conducted research in home health care (n = 17). Consensus
      emerged after three rounds, with the four most important priorities identified as
      outcomes, health policy, the use of advanced practice nurses, and models of
      care/best practice. These areas are consistent with the regulatory events in home
      health care in the last 10 years.

PMID- 16298699
TI  - Development of advanced practice nurses in South Korea.
AB  - In Korea, since the first specialized areas of nursing were first recognized in
      1973, 10 areas have been established by the Medicine Law, 2003: public health,
      anesthesia, mental health, home care nursing, gerontological nursing, critical
      care nursing, industrial nursing, hospice, emergency nursing, and infection
      control. Education for advanced practice nurses is the MSN level curriculum
      requiring 33 credit semester hours or more. However, there are several problems
      to be solved and challenges to be overcome before offering advanced nursing
      practice to the population. Those tasks and their plausible solutions were
      discussed in the article.

PMID- 16298701
TI  - Evidence-based nursing: making changes in the clinical practice through the
      collaboration of nursing students and practicing nurses.
AB  - The collaboration between student nurses and practicing clinical nurses on an
      evidence-based project is described. This collaboration sought to answer a
      question pertinent to the needs of the clinical nurses, while providing the
      students with an excellent practical learning opportunity. The changes in both
      knowledge and practice resulting from this partnership are described.

PMID- 16298705
TI  - Photographing wheelchair-bound patients with neuromuscular scoliosis in a
      paediatric hospital.
AB  - This is an investigation of the photography services offered to children and
      adolescents with neuromuscular scoliosis at the spinal inpatient and outpatient
      clinic of Great Ormond Street Hospital. The spine service, in cooperation with
      the medical photography department, sought to identify what clinicians required
      in the content of photographs as part of the patients' routine clinical
      assessment, and also what equipment was available on the market to meet these
      requirements. Current techniques for obtaining medical photographs of this
      specific group of severely disabled children were also evaluated, and compared to
      a proposed method of obtaining photographs using the Mangar chair. The authors
      sought to develop a safe, reliable, patient-friendly and parent-friendly, and
      easily reproducible technique, which would provide accurate and consistent
      photographs, and adequately supplement the clinicians' evaluation of patients'
      conditions.

PMID- 16298706
TI  - Dermatology--here and now.
AB  - Dermatology is a branch of medicine that benefits from the use of photography, to
      assist in diagnosis and teaching through clinical discussion of the physical
      signs of a disease, and thereafter, for the monitoring of the condition
      throughout treatment. This paper describes the development of a dedicated medical
      photography service in the Welsh Institute of Dermatology at the University
      Hospital of Wales, Cardiff and Vale NHS Trust. As a consequence, a close working
      relationship has developed between the dermatologists and the photographers,
      leading to some interesting new approaches in the use of photography to enhance
      patient care.

PMID- 16298707
TI  - Standardization in clinical photography at Addenbrooke's Hospital.
AB  - Most, if not all, medical illustration departments in the UK provide medical
      photography as a principal service. The author believes that all work undertaken
      by qualified medical photographers must be of a uniformly high standard, and
      argues that departmental protocols exemplify the quality of work expected of
      staff, and help to ensure uniformity throughout a department. This paper outlines
      the procedure followed by staff within the Medical Photography Department at
      Addenbrooke's Hospital, Cambridge.

PMID- 16298708
TI  - The photography of bruises.
AB  - This pilot study demonstrates four different photographic lighting techniques
      (using visible, red free, infrared and ultraviolet) with digital technology to
      record a bruise. It is suggested that it may be possible to record accurately the
      size of a bruise at different stages from injury to healing, using one or more of
      these techniques.

PMID- 16298711
TI  - Typical 'smoke stack CSR': a case report.

PMID- 16298712
TI  - Clinical photography of scoliosis.
AB  - The IMI National Guidelines have been prepared as baseline guides on specific
      aspects of medical illustration practice, and provide auditable standards for the
      future. They can be implemented in full, or may be amended according to
      individual requirements. The following, prepared by Mike Devlin, is the second in
      the series to be published in this Journal. This and the other guidelines can be
      read or downloaded at: www.imi.org.uk.

PMID- 16298716
TI  - What's new in nicotine & tobacco research?

PMID- 16298717
TI  - Guidance for research and testing to reduce tobacco toxicant exposure.

PMID- 16298718
TI  - Methods to assess potential reduced exposure products.
AB  - The availability of tobacco products purported to reduce toxin exposure or
      potentially reduce health risks necessitates the development of methods and
      identification of biomarkers that can be used to assess these products. These
      assessments occur on multiple levels and stages, from identifying constituents in
      the tobacco products and smoke, to human exposure and health effects trials, to
      postmarketing surveillance. A conference of multidisciplinary experts was
      convened to present and discuss methods and biomarkers to assess these products
      and to consider the infrastructure necessary to facilitate the evaluation
      process. Although no currently available set of measures was thought to be
      sufficient for determining the relative health risk of potential reduced exposure
      products, this paper provides a blueprint for future research toward this end.

PMID- 16298719
TI  - Predicting the stages of smoking acquisition in the male students of Shiraz's
      high schools, 2003.
AB  - A staged model of smoking adoption has been widely applied in studies of
      adolescent smoking. This paper examined the effects of socioenvironmental and
      personal factors on three stages of the smoking continuum among a sample of 10th
      grade male students, ages 14-19 years, at 20 high schools in Shiraz city. This
      paper is the first step of a longitudinal study related to adolescents smoking
      and predictors of transition in the stages. A self-administered questionnaire was
      distributed to 1,132 10th-grade students from a possible population of 14,000
      students. Multivariate discriminant function analysis was used to analyze the
      data. Overall 19.4% of students had smoked; 80.6%, 16.9%, and 2.5% had never
      smoked, had experimented, and had regularly smoked, respectively. The
      discriminant function analysis indicated that attitude toward smoking, use of
      alcohol, use of illicit drugs, smoking behavior of best friends, and self-esteem
      were related to more intense smoking behaviors. Finally, these variables
      permitted the correct classification of 70.3% of students into the stages of
      smoking acquisition. This finding has important public health significance, but
      further research is required to determine if the association is causal.

PMID- 16298720
TI  - Associations between phenylthiocarbamide gene polymorphisms and cigarette
      smoking.
AB  - Phenotypic evidence indicates that the ability to taste the bitter compounds
      phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) may protect against
      cigarette smoking. In this study, PTC gene haplotypes were found to be associated
      with both the odds of being a smoker and the importance of cigarette taste as a
      smoking motive. Smokers (n = 384) and nonsmokers (n = 183) were genotyped for
      polymorphisms that affect taste sensitivity to PTC and PROP. The "taster" PAV
      haplotype, relative to the "nontaster" AVI haplotype, was predicted to be
      associated with reduced odds of being a smoker and lower taste motivation as
      measured by the Wisconsin Inventory of Smoking Dependence Motives-68
      taste/sensory processes scale. The results did not support the predicted
      association between the PAV and AVI haplotypes and smoker odds, but the AAV
      haplotype, which confers intermediate PTC/PROP taste sensitivity, was associated
      with reduced smoker prevalence (49% vs. 70%), chi(2)(1, N = 567) = 10.392, p =
      .001. The predicted relationship between PAV and AVI and taste motivation was
      found, F(2, 348) = 3.303, p = .038. The results encourage further exploration of
      the role of taste/sensory processes in tobacco dependence.

PMID- 16298721
TI  - The influence of depressive symptoms on smoking cessation among African Americans
      in a randomized trial of bupropion.
AB  - The influence of depressive symptoms on smoking cessation was examined among 600
      African American smokers who participated in a randomized, placebo-controlled
      trial of sustained-release bupropion hydrochloride. Depressive symptoms were
      assessed at baseline, at week 6 (end of treatment), and at 6-month follow-up. The
      study examined three separate questions: (a) Whether depressive symptom levels
      were related to smoking cessation, (b) whether bupropion was more effective for
      smokers who had higher depressive symptoms at baseline (i.e., a moderator model),
      and (c) whether changes in depressive symptoms would account for the efficacy of
      bupropion for smoking cessation (i.e., a mediator model). Depressive symptoms at
      baseline were not predictive of cessation; however, increases in depressive
      symptoms from baseline predicted reduced cessation at the end of treatment, and
      higher depressive symptoms at week 6 and month 6 were associated with a reduced
      likelihood of smoking cessation at those time points. The moderator model was not
      supported, but the mediation analyses indicated that alleviation of depressive
      symptoms partly accounted for bupropion-assisted smoking cessation at end of
      treatment. Results extend prior findings to African American smokers and suggest
      that clinicians consider increases in depressive symptoms after quitting rather
      than baseline depressive symptoms in predicting risk of treatment failure.
      Results also suggest that even though bupropion may facilitate cessation in part
      by reducing depressive symptoms, it appears to be no more effective for more
      depressed smokers, and that mechanisms other than depressive symptom alleviation
      account for most of its efficacy.

PMID- 16298722
TI  - The efficacy of moderate-intensity exercise as an aid for smoking cessation in
      women: a randomized controlled trial.
AB  - Evidence suggests that vigorous-intensity exercise interventions may be effective
      for smoking cessation among women; however, few studies have examined the
      efficacy of a moderate-intensity exercise program. The present study examined the
      efficacy of moderate-intensity exercise for smoking cessation among female
      smokers. Healthy, sedentary female smokers (N = 217) were randomly assigned to an
      8-week cognitive-behavioral smoking cessation program plus moderate-intensity
      exercise (CBT+EX) or to the same cessation program plus equal contact (CBT). A
      subsample received nicotine replacement therapy. Results indicated that the
      CBT+EX and CBT groups were equally likely to attain smoking cessation at the end
      of treatment, as measured by cotinine-verified 7-day point-prevalence abstinence
      (20.2% for CBT+EX vs. 18.5% for CBT). The CBT+EX group was more likely to report
      smoking cessation, as measured by 7-day point prevalence at the 3-month follow-up
      (11.9% vs. 4.6%, p<.05), compared with the CBT group. No group differences were
      found at 12 months by either 7-day point prevalence (7.3% for CBT+EX vs. 8.3% for
      CBT) or continuous abstinence (0.9% for CBT+EX vs. 0.9% for CBT). Additionally,
      among participants in the CBT+EX group, those with higher adherence to the
      exercise prescription were significantly more likely to achieve smoking cessation
      at the end of treatment than were participants reporting lower adherence to
      exercise. Our findings indicate that the empirical support for moderate-intensity
      exercise as an adjunctive treatment to CBT for smoking cessation may be limited.
      Perhaps future studies could compare moderate- vs. vigorous-intensity physical
      activity to test their relative efficacy.

PMID- 16298723
TI  - Proactive, motivationally enhanced smoking cessation counseling among women with
      elevated cervical cancer risk.
AB  - Current treatment guidelines recommend that all smokers be given motivational or
      action-oriented counseling, as is appropriate to their readiness to quit smoking.
      The present study assessed the acceptability and impact of a proactively
      delivered, motivationally tailored phone counseling program targeted to women
      with elevated risk for cervical cancer. Female smokers with a recent abnormal pap
      exam or a colposcopy were contacted and invited to participate, regardless of
      their interest in quitting smoking. Participants were randomly assigned to usual
      care (UC) or UC plus motivationally enhanced phone counseling (MEC). The
      intervention was well received: 79% of eligible women enrolled (n = 275), and 90%
      completed at least three of four calls. Participation did not vary by baseline
      motivation to quit. Compared with control subjects, counseling participants were
      more likely to seek additional treatment services and had a higher 7-day point
      prevalence abstinence rate at 6 months (20% MEC vs. 12% UC, p<.05). MEC impact
      was sustained at 12 months, but abstinence increased among the UC group (18% MEC
      vs. 20% UC, p = ns). There was no difference in repeated point-prevalence
      abstinence at 6 and 12 months (11% MEC vs. 10% UC, p = ns). Outcomes were similar
      in a subgroup of 229 women who, at baseline, were interested in quitting in the
      next 6 months.

PMID- 16298724
TI  - Tobacco control policies and the concurrent use of smokeless tobacco and
      cigarettes among men, 1992-2002.
AB  - Accelerating the decline in smoking prevalence requires an understanding of
      changes in the concurrent use of and the substitution between different tobacco
      products, such as smokeless tobacco (SLT) and cigarettes. SLT could play an
      important role in reducing the toll of smoking-related illness and premature
      mortality. Research examining the role of tobacco control policies in explaining
      concurrent use of SLT and cigarettes has been minimal. Using the Current
      Population Survey Tobacco Use Supplements (CPS-TUS), we examined tobacco control
      policies in relationship with adult males' SLT use concurrent with smoking over
      the period 1992-2002. Consistent with the decline in smokeless-only and cigarette
      only rates, concurrent use of SLT and cigarettes declined during the period. SLT
      users, faced with home or workplace smoking bans, are less likely to report
      smoking. Smokers with a home ban appear more likely to use SLT, but in more
      recent years, smokers with a workplace ban are less likely to use SLT. Tobacco
      excise taxes do not signal substitution between cigarettes and SLT products.
      Understanding current use patterns of the range of tobacco products, including
      their interaction with available policy levers, is vital in assessing whether
      changes that might promote substitution of arguably less toxic SLT products for
      highly toxic cigarettes are likely to lead to net public health gains or losses.
      Findings of the present study, in concert with other research about transitional
      probabilities between behavioral states, will inform the design of an effective
      policy framework that supports the objective of reducing tobacco-related death
      and disease.

PMID- 16298725
TI  - Tolerance does not develop to the decrease in nicotine self-administration
      produced by repeated bupropion administration.
AB  - The atypical antidepressant bupropion has been shown to be an efficacious smoking
      cessation agent; however, its therapeutic mechanism of action is unknown. To
      further understand the mechanism by which bupropion reduces smoking, the present
      study determined the effect of repeated bupropion pretreatment on nicotine self
      administration or sucrose-maintained responding. Rats were trained to self
      administer intravenous nicotine (0.02 mg/kg/infusion; Experiment 1) or to respond
      for sucrose pellets (45 mg each; Experiment 2) on a fixed-ratio 5 schedule. Once
      rats reached stable responding, bupropion (70 mg/kg, subcutaneously) or vehicle
      was injected 15 min before the session for 14 consecutive sessions. Bupropion
      acutely decreased both nicotine self-administration and sucrose-maintained
      responding by approximately 60%-70%. With repeated bupropion pretreatment,
      however, responding for nicotine decreased completely. In contrast, the bupropion
      induced decrease in responding for sucrose following acute administration did not
      change significantly with repeated bupropion administration. These results
      suggest that bupropion acquired some specificity with repeated use, decreasing
      the intake of nicotine and producing an extinction-like pattern in nicotine self
      administration. Thus the present results parallel human clinical studies with
      bupropion demonstrating its smoking cessation properties following repeated
      treatment. These results indicate that the rat nicotine self-administration
      paradigm is a useful animal model for assessing smoking cessation
      pharmacotherapies.

PMID- 16298726
TI  - "Withdrawal symptoms" in adolescents: a comparison of former smokers and never
      smokers.
AB  - Since the early 1980s, investigators have been reporting that adolescent smokers
      felt "dependent" on cigarettes and that adolescents trying to quit smoking
      experienced the same withdrawal symptoms observed in adult quitters, including
      restlessness, insomnia, increased appetite and weight gain, irritability or
      anger, depression, craving for cigarettes, and trouble concentrating. We
      hypothesized that most of these symptoms might be attributed to adolescence
      itself. To investigate this hypothesis, we examined the prevalence of these seven
      "adult" withdrawal symptoms in a population of adolescent former smokers and
      never-smokers. Participants were high school students in Houston, Texas,
      participating in a nested, group-randomized control group study designed to
      estimate the impact of a CD-ROM intervention for smoking prevention and
      cessation. We measured differences in symptoms frequency between never-smokers
      and former smokers, matched in a 2:1 ratio on sex and race/ethnicity, and
      differences in symptoms among former smokers as a function of time since final
      quit attempt and prior level of smoking. Only former heavy smokers have shown
      significantly higher prevalence of withdrawal symptoms compared with never
      smokers. Of the seven symptoms assessed, only craving incrementally increased
      with the intensity of smoking. Overall the individual withdrawal symptoms did not
      effectively differentiate between 112 never-smokers and 34 former lighter smokers
      (persons who used to smoke less than "a few cigarettes on most days"). Withdrawal
      symptoms can reliably differentiate former heavy smokers from light smokers and
      never-smokers, among adolescents. Because most adolescents tend to be lighter
      smokers, future tobacco use and cessation studies should interpret adult
      withdrawal symptoms among adolescents with caution.

PMID- 16298727
TI  - Comment on Shiffman and colleagues, "Nicotine patch and lozenge are effective for
      women".

PMID- 16298728
TI  - Spin trapping nitric oxide from neuronal nitric oxide synthase: A look at several
      iron-dithiocarbamate complexes.
AB  - The free radical, nitric oxide ( radicalNO), is responsible for a myriad of
      physiological functions. The ability to verify and study radicalNO in vivo is
      required to provide insight into the events taking place upon its generation and
      in particular the flux of radicalNO at relevant cellular sites. With this in
      mind, several iron-chelates (Fe2+(L)2) have been developed, which have provided a
      useful tool for the study and identification of radicalNO through spin-trapping
      and electron paramagnetic resonance (EPR) spectroscopy. However, the
      effectiveness of radicalNO detection is dependent on the Fe2+(L)2 complex. The
      development of more efficient and stable Fe2+(L)2 chelates may help to better
      understand the role of radicalNO in vivo. In this paper, we present data
      comparing several proline derived iron-dithiocarbamate complexes with the more
      commonly used spin traps for radicalNO, Fe2+-di(N-methyl-D-glutamine
      dithiocarbamate) (Fe2+(MGD)2) and Fe2+-di(N-(dithiocarboxy)sarcosine)
      (Fe2+(DTCS)2). We evaluate the apparent rate constant (kapp) for the reaction of
      radicalNO with these Fe2+(L)2complexes and the stability of the corresponding
      Fe2+(NO)(L)2 in presence of NOS I.

PMID- 16298729
TI  - Involvement of oxidative stress in hydroquinone-induced cytotoxicity in catalase
      deficient Escherichia coli mutants.
AB  - Hydroquinone is a benzene-derived metabolite. To clarify whether the reactive
      oxygen species (ROS) are involved in hydroquinone-induced cytotoxicity, we
      constructed transformants of Escherichia coli (E. coli) strains that express
      mammalian catalase gene derived from catalase mutant mice (Cs(b), Cs(c)) and the
      wild-type (Cs(a)) using a catalase-deficient E. coli UM255 as a recipient.
      Specific catalase activities of these tester strains were in order of Cs(a) >
      Cs(c) > Cs(b) > UM255, and their susceptibility to hydrogen peroxide (H2O2)
      showed UM255 > Cs(b) > Cs(c) > Cs(a). We found that hydroquinone exposure reduced
      the survival of catalase-deficient E. coli mutants in a dose-dependent manner
      significantly, especially in the strains with lower catalase activities.
      Hydroquinone toxicity was also confirmed using zone of inhibition test, in which
      UM255 was the most susceptible, showing the largest zone of growth inhibition,
      followed by Cs(b), Cs(c) and Cs(a). Furthermore, we found that hydroquinone
      induced cell damage was inhibited by the pretreatment of catalase, ascorbic acid,
      dimethyl sulfoxide (DMSO), and ethylenediaminetetraacetic acid (EDTA), and
      augmented by superoxide dismutase (both CuZnSOD and MnSOD). The present results
      suggest that H2O2 is probably involved in hydroquinone-induced cytotoxicity in
      catalase-deficient E. coli mutants and catalase plays an important role in
      protection of the cells against hydroquinone toxicity.

PMID- 16298730
TI  - Initiation of a superoxide-dependent chain oxidation of lactate dehydrogenase
      bound NADH by oxidants of low and high reactivity.
AB  - In cells, NADH and NADPH are mainly bound to dehydrogenases such as lactate
      dehydrogenase (LDH). In cell-free systems, the binary LDH-NADH complex has been
      demonstrated to produce reactive oxygen species via a chain oxidation of NADH
      initiated and propagated by superoxide. We studied here whether this chain
      radical reaction can be initiated by oxidants other than LDH largely increased
      the oxidation of NADH (but not of NADPH) by O(2), H(2)O(2) and during the
      intermediacy of HNO(2). LDH also increased the oxidation of NADH by
      peroxynitrite. The increases in NADH oxidation were completely prevented by
      superoxide dismutase (SOD). In contrast, the nitrogen dioxide-dependent oxidation
      of NADH and NADPH was decreased by LDH in a SOD-independent manner. These
      experimental data strongly indicate that oxidation of LDH-bound NADH can be
      induced from reaction of either weak oxidants with LDH-bound NADH or of strong
      oxidants with free NADH thus yielding which is highly effective to propagate the
      chain. Our results underline the importance of SOD in terminating superoxide
      dependent chain reactions in cells under oxidative stress.

PMID- 16298731
TI  - Cadmium effects on ros production and DNA damage via adrenergic receptors
      stimulation: role of Na+/H+ exchanger and PKC.
AB  - The objective of the present study was to elucidate the events that are involved
      in reactive oxygen species (ROS) production and DNA damage after adrenergic
      receptors stimulation by cadmium, in relation to cAMP, protein kinase C (PKC) and
      Na+/H+ exchanger (NHE). Cadmium (50 microM) caused increased levels of ROS with a
      concomitant increase in DNA damage in digestive gland of Mytilus
      galloprovincialis. Either the use of EIPA, a NHE blocker, or calphostin C, the
      inhibitor of PKC, reduced cadmium effects. Cells treated with alpha1-, alpha2-,
      beta- and beta1- adrenergic antagonists together with cadmium reversed cadmium
      alone effects, while the respective adrenergic agonists, phenylephrine and
      isoprenaline, mimic cadmium effects. Moreover, cadmium caused an increase in the
      levels of cAMP in digestive gland cells that were reversed after NHE and PKC
      inhibition as well as in the presence of each type of adrenergic antagonist. The
      different sensitivity of alpha1-, alpha2-, beta-, beta1- adrenergic receptors on
      ROS, cAMP production and DNA damage possibly leads to the induction of two
      signaling pathways that may be interacting or to the presence of a compensatory
      pathway that acts in concert with the alpha- and beta- adrenergic receptors. In
      these signaling pathways PKC and NHE play significant role.

PMID- 16298732
TI  - Comparative study of the formation of oxidative damage marker 8-hydroxy-2'
      deoxyguanosine (8-OHdG) adduct from the nucleoside 2'-deoxyguanosine by
      transition metals and suspensions of particulate matter in relation to metal
      content and redox reactivity.
AB  - An association between exposure to ambient particulate matter (PM) and increased
      incidence of mortality and morbidity due to lung cancer and cardiovascular
      diseases has been demonstrated by recent epidemiological studies. Reactive oxygen
      species (ROS), especially hydroxyl radicals, generated by PM, have been suggested
      by many studies as an important factor in the oxidative damage of DNA by PM. The
      purpose of this study was to characterize quantitatively hydroxyl radical
      generation by various transition metals in the presence of H2O2 in aqueous buffer
      solution (pH 7.4) and hydroxylation of 2'-deoxyguanosine (dG) to 8-hydroxy-2'
      deoxyguanosine (8-OHdG) under similar conditions. The order of metals' redox
      reactivity and hydroxyl radical production was Fe(II), V(IV), Cu(I), Cr(III),
      Ni(II), Co(II), Pb(II), Cd(II). Then, we investigated the generation of hydroxyl
      radicals in the presence of H2O2 by various airborne PM samples, such as total
      suspended particulate (TSP), PM10, PM2.5 (PM with aerodynamic diameter 10 and 2.5
      microm), diesel exhaust particles (DEP), gasoline exhaust particles (GEP) and
      woodsmoke soot under the same conditions. When suspensions of PMs were incubated
      with H2O2 and dG at pH 7.4, all particles induced hydroxylation of dG and
      formation of 8-OHdG in a dose-dependent increase. Our findings demonstrated that
      PM's hydroxyl radical (HO radical) generating ability and subsequent dG
      hydroxylation is associated with the concentration of water-soluble metals,
      especially Fe and V and other redox or ionizable transition metals and not their
      total metal content, or insoluble metal oxides, via a Fenton-driven reaction of
      H2O2 with metals. Additionally, we observed, by Electron paramagnetic resonance
      (EPR), that PM suspensions in the presence of H2O2 generated radical species with
      dG, which were spin-trapped by 2-methyl-2-nitroso-propane (MNP).

PMID- 16298733
TI  - Role of calcium-induced mitochondrial hydroperoxide in induction of apoptosis of
      RBL2H3 cells with eicosapentaenoic acid treatment.
AB  - Eicosapentaenoic acid (EPA) was previously shown to induce caspase-independent
      apoptosis in rat basophilic leukemia cells (RBL2H3 cells) by translocation of
      apoptosis-inducing factor (AIF) [Free Radic Res (2005) 39, 225-235]. Here, we
      attempted to investigate the mechanism of EPA-induced apoptosis. A rapid and
      sustained increase in calcium was observed in mitochondria at 2 h after the
      addition of EPA prior to apoptosis. Coincidently, hydroperoxide was generated in
      the mitochondria after exposure to EPA. Production of mitochondrial hydroperoxide
      was significantly reduced by ruthenium red, an inhibitor of mitochondrial calcium
      uniporter, and BAPTA-AM, a cytoplasmic calcium chelator, indicating that
      generation of hydroperoxide is triggered by an accumulation of calcium in the
      mitochondria. The production of mitochondrial hydroperoxide was markedly
      attenuated by overexpression of phospholipid hydroperoxide glutathione peroxidase
      (PHGPx) in the mitochondria. Apoptosis was therefore, significantly prevented
      through inhibition of mitochondrial hydroperoxide generation with mitochondrial
      PHGPx, ruthenium red or BAPTA-AM. However, accumulation of calcium in the
      mitochondria was not prevented by mitochondrial PHGPx although apoptosis was
      blocked, indicating that elevated calcium does not directly induce apoptosis.
      Taken together, our results show that calcium-dependent hydroperoxide
      accumulation in the mitochondria is critical in EPA-induced apoptosis.

PMID- 16298734
TI  - Association of DJ-1 with chaperones and enhanced association and colocalization
      with mitochondrial Hsp70 by oxidative stress.
AB  - DJ-1 is a novel oncogene and causative gene for familial form of the Parkinson's
      disease (PD). DJ-1 has been shown to play a role in anti-oxidative stress by
      eliminating reactive oxygen species (ROS). The onset of PD is thought to be
      caused by oxidative stress and mitochondrial injury, which leads to protein
      aggregation that results in neuronal cell death. However, the mechanism by which
      DJ-1 triggers the onset of PD is still not clear. In this study, we analyzed
      association and localization of DJ-1 and its mutants with various chaperones. The
      results showed that DJ-1 and its mutants were associated with Hsp70, CHIP and
      mtHsp70/Grp75, a mitochondria-resident Hsp70, and that L166P and M26I mutants
      found in PD patients were strongly associated with Hsp70 and CHIP compared to
      wild-type and other DJ-1 mutants. DJ-1 and its mutants were colocalized with
      Hsp70 and CHIP in cells. Furthermore, association and colocalization of wildtype
      DJ-1 with mtHsp70 in mitochondria were found to be enhanced by treatment of cells
      with H2O2. These results suggest that translocation of DJ-1 to mitochondria after
      oxidative stress is carried out in association with chaperones.

PMID- 16298735
TI  - Suppression of oxidative stress in aging NZB/NZW mice: effect of fish oil feeding
      on hepatic antioxidant status and guanidino compounds.
AB  - Oxidative stress caused by excessive reactive species (RS) and lipid peroxidation
      is known to be casually linked to age-related inflammation. To test the
      hypothesis that fish oil (FO) intake has a beneficial effect on nephritis due to
      its suppressive action of oxidative stress and the enhancement of antioxidant
      defenses, we examined the effect of dietary FO on various oxidative stress
      related parameters and guanidino compound (GC) levels using (NZB x NZW) F1 (B/W)
      mice. These mice were fed diets supplemented with either 5% corn oil (control) or
      5% FO. At 4 and 9 months of age, the hepatic oxidative status was estimated by
      assessing RS generation produced from xanthine oxidase, the prostaglandin pathway
      and lipid peroxidation. To evaluate the effect of FO on redox status, including
      antioxidant defenses, GSH and GSSG levels and antioxidant enzyme activities were
      measured. To correlate the extent of oxidative status with the nephritic
      condition, creatinine, guanidino acetic acid and arginine levels were measured.
      Results indicated that increased levels of lipid peroxidation, RS generation and
      xanthine oxidase activity with age were all significantly suppressed by FO
      feeding. Furthermore, reduced GSH levels, GSH/GSSG ratio and antioxidant enzyme
      activities in the FO-fed mice were effectively enhanced compared to the corn oil
      fed mice. Among several GCs, the age-related increase of creatinine level was
      blunted by FO. Based on these results, we propose that dietary FO exerts
      beneficial effects in aged, nephritic mice by suppressing RS, superoxide and
      lipid peroxidation, and by maintaining a higher GSH/GSSG ratio and antioxidant
      enzyme activities.

PMID- 16298736
TI  - Oxygen therapy at low flow causes oxidative stress in chronic obstructive
      pulmonary disease: Prevention by N-acetyl cysteine.
AB  - Exposure to high oxygen concentration produces toxicity by free radical release.
      We aimed to study: whether stable chronic obstructive pulmonary disease (COPD)
      patients present an unbalance in the blood redox status; the effect of oxygen
      administration on blood redox balance; the efficacy of N-acetyl-cysteine (NAC)
      treatment against the oxidative stress-induced by oxygen administration and
      whether it is dose-related. To this, 45 stable state III COPD patients were
      recruited and reduced glutathione (GSH) and oxidised glutathione (GSSG) in
      erythrocytes and thiol proteins (P-SH) and carbonyl proteins (PC) in both
      erythrocytes and plasma were evaluated. All COPD patients underwent 2 l/m oxygen
      for 18 h and NAC at 1200 or 1800 mg/day or placebo for 48 h starting with oxygen
      administration. Blood samples were collected at basal conditions, after 8 and 18
      h of oxygen administration and 24 h after oxygen withdrawal. RESULTS: COPD
      patients present an unstable redox equilibrium mainly due to plasma sulphydryl
      protein depletion. Oxygen administration oxidize erythrocyte GSH, decrease P-SH
      and increase PC levels in both plasma and erythrocytes. NAC administration
      counteract the oxidative stress and at the highest dose completely prevent
      protein oxidation. In conclusion, stable state III COPD patients present an
      unstable redox balance; long term low flow oxygen administration induces systemic
      oxidative stress, which is prevented by NAC treatment.

PMID- 16298737
TI  - Neuroprotective properties of the natural phenolic antioxidants curcumin and
      naringenin but not quercetin and fisetin in a 6-OHDA model of Parkinson's
      disease.
AB  - Although the cause of dopaminergic cell death in Parkinson's disease (PD) remains
      unknown, oxidative stress has been strongly implicated. Because of their ability
      to combat oxidative stress, diet derived phenolic compounds continue to be
      considered as potential agents for long-term use in PD. This study was aimed at
      investigating whether the natural phenolic compounds curcumin, naringenin,
      quercetin, fisetin can be neuroprotective in the 6-OHDA model of PD. Unilateral
      infusion of 6-OHDA into the medial forebrain bundle produced a significant loss
      of tyrosine hydroxylase (TH)-positive cells in the substantia nigra (SN) as well
      as a decreased of dopamine (DA) content in the striata in the vehicle-treated
      animals. Rats pretreated with curcumin or naringenin showed a clear protection of
      the number of TH-positive cells in the SN and DA levels in the striata. However,
      neither pretreatment with quercetin nor fisetin had any effects on TH-positive
      cells or DA levels. The ability of curcumin and naringenin to exhibit
      neuroprotection in the 6-OHDA model of PD may be related to their antioxidant
      capabilities and their capability to penetrate into the brain.

PMID- 16298738
TI  - Vitamin E deficiency induces liver nuclear factor-kappaB DNA-binding activity and
      changes in related genes.
AB  - The biological functions of vitamin E have been classically attributed to its
      property as a potent inhibitor of lipid peroxidation in cellular membranes.
      However, in 1991, Azzi's group first described that alpha-tocopherol inhibits
      smooth muscle cell proliferation in a protein kinase C (PKC)-dependent way,
      demonstrating a non-antioxidant cell signalling function for vitamin E. More
      recently, the capacity of alpha-tocopherol to modulate gene expression with the
      implication of different transcription factors, beyond its antioxidant
      properties, has also been established. This study was to determine the effect of
      vitamin E-deficiency on liver nuclear factor-kappa B (NF-kappaB) DNA-binding
      activity and the response of target antioxidant-defense genes and cell cycle
      modulators. Rats were fed either control diet or vitamin-E free diet until 60 or
      90 days after birth. Vitamin E-deficiency enhanced liver DNA-binding activity of
      NF-kappaB [electrophoretic mobility-shift assay, (EMSA)] and up-regulated
      transcription of gamma-glutamylcysteine synthetase (gamma-GCSM; gamma-GCSC),
      cyclin D1 and cyclin E. We also showed down-regulation of p21(Waf1/Cip1)
      transcription. Western-blot analysis demonstrated that gamma-glutamylcysteine
      synthetase catalytic subunit (gamma-GCSC) and cyclin D1 showed a similar pattern
      to that found in the RT-PCR analysis. Moreover, chromatin immunoprecipitation
      (ChIP) assay demonstrated that NF-kappaB directly regulates transcription of
      gamma-GCS (both subunits) and cyclin D1 through the binding of NF-kappaB to the
      corresponding gene promoters, which was enhanced in vitamin E-deficiency. These
      findings show that vitamin E-deficiency induces significant molecular regulatory
      properties in liver cells with an altered expression of both antioxidant-defense
      genes and genes that control the cell cycle and demonstrate that liver NF-kappaB
      activation is involved in this response. Our results emphasize the importance of
      maintaining an adequate vitamin E consumption not only to prevent liver oxidative
      damage but also in modulating signal transduction.

PMID- 16298739
TI  - Intestinal absorption and metabolism of a soluble flavonoid, alphaG-rutin, in
      portal cannulated rats.
AB  - A highly soluble quercetin glycoside, alphaG-rutin, is a glucose adduct of
      insoluble rutin, and intestinal absorption and metabolism of alphaG-rutin has not
      been known. We investigated the intestinal absorption and metabolism of alphaG
      rutin by using portal and duodenal cannulated rats and the isolated rat
      intestinal mucosa. After a duodenal instillation of alphaG-rutin (150 mumol),
      intact alphaG-rutin, rutin and quercetin were appeared in the portal blood and
      these concentrations were similarly increased at 15 min. Portal quercetin reached
      a peak value at 60 min, and the value was higher than those of alphaG-rutin and
      rutin at that time. Quercetin-conjugates were also increased 30 min after the
      instillation. The remaining of alphaG-rutin metabolites, mainly rutin, in the
      intestine were 58% of instilled alphaG-rutin after 150 min. In the experiment by
      using the isolated mucosa of the jejunum, ileum and cecum, alphaG-rutin and
      rutin, but not quercetin, appeared in the serosal sides of all segments, and they
      were increased linearly from 10 to 100 mmol/l of mucosal alphaG-rutin. We also
      showed portal injected alphaG-rutin was very rapidly cleared from the blood, and
      appeared a large amount of conjugates. In conclusion, a soluble flavonoid
      glycoside, alphaG-rutin, was absorbed as glycosides into the portal blood. A part
      of alphaG-rutin was hydrolyzed to rutin, but not to aglycone, through the
      intestine.

PMID- 16298740
TI  - Free radical mediated oxidative stress and toxic side effects in brain induced by
      the anti cancer drug adriamycin: insight into chemobrain.
AB  - Adriamycin (ADR) is a chemotherapeutic agent useful in treating various cancers.
      ADR is a quinone-containing anthracycline chemotherapeutic and is known to
      produce reactive oxygen species (ROS) in heart. Application of this drug can have
      serious side effects in various tissues, including brain, apart from the known
      cardiotoxic side effects, which limit the successful use of this drug in
      treatment of cancer. Neurons treated with ADR demonstrate significant protein
      oxidation and lipid peroxidation. Patients under treatment with this drug often
      complain of forgetfulness, lack of concentration, dizziness (collectively called
      somnolence or sometimes called chemobrain). In this study, we tested the
      hypothesis that ADR induces oxidative stress in brain. Accordingly, we examined
      the in vivo levels of brain protein oxidation and lipid peroxidation induced by
      i.p. injection of ADR. We also measured levels of the multidrug resistance
      associated protein (MRP1) in brain isolated from ADR- or saline-injected mice.
      MRP1 mediates ATP-dependent export of cytotoxic organic anions, glutathione S
      conjugates and sulphates. The current results demonstrated a significant increase
      in levels of protein oxidation and lipid peroxidation and increased expression of
      MRP1 in brain isolated from mice, 72 h post i.p injection of ADR. These results
      are discussed with reference to potential use of this redox cycling
      chemotheraputic agent in the treatement of cancer and its chemobrain side effect
      in brain.

PMID- 16298741
TI  - Protective effect of capsinoid on lipid peroxidation in rat tissues induced by Fe
      NTA.
AB  - The activity of a single IP administration (15 or 30 mg/Kg body weight) of
      vanillyl nonanoate, a simplified analog of capsiate, on ferric nitrilotriacetate
      (Fe-NTA)-mediated oxidative damage was investigated. A sub-lethal dose of Fe-NTA
      (15 mg Fe/Kg body weight) was administered IP to rats; animals were sacrificed,
      and kidney and plasma were collected 1 h after injection. In response to the Fe
      NTA administration, a reduction of the levels of total lipids, total unsaturated
      fatty acids and cholesterol was observed, accompanied by a rise in the
      concentrations of malondialdehyde (MDA), conjugated dienes fatty acids
      hydroperoxides and 7-ketocholesterol in plasma and kidney 1 h after
      administration. A pre-treatment with synthetic capsiate (SCPT) showed remarkable
      protective effect on the reduction of the levels of total lipids, total
      unsaturated fatty acids and cholesterol, and the cellular antioxidant vitamin E,
      inhibiting the increase of MDA, conjugated dienes fatty acids hydroperoxides and
      7-ketocholesterol in the plasma and kidney. The protective effect of SCPT and two
      analogues (vanillyl alcohol and vanillin) during the linoleic acid and
      cholesterol oxidation was investigated in in vitro systems, providing evidence of
      definite structure-activity relationships.

PMID- 16298742
TI  - Free radical scavenging reactions of sulfasalazine, 5-aminosalicylic acid and
      sulfapyridine: mechanistic aspects and antioxidant activity.
AB  - Reactions of sulfasalazine (SAZ) and its metabolites, 5-aminosalicylic acid (5
      ASA) and sulfapyridine (SP), with various oxidizing and reducing free radicals
      (hydroxyl, haloperoxyl, one-electron oxidizing, lipid peroxyl, glutathiyl,
      superoxide, tryptophanyl, etc.) have been studied to understand the mechanistic
      aspects of its action against free radicals produced during inflammation.
      Nanosecond pulse radiolysis technique coupled with transient spectrophotometry
      has been used for in situ generation of free radicals and to follow their
      reaction pathways. The transients produced in these reactions have been assigned
      and radical scavenging rate constants have been measured. In addition to
      scavenging of various primary and secondary free radicals by SAZ, 5-ASA and SP, 5
      ASA has also been observed to efficiently scavenge radicals of biomolecules. 5
      ASA has been found to be the active moiety of SAZ involved in the scavenging of
      oxidizing free radicals whereas reduction of SAZ produced molecular radical
      anion. The study suggests that free radical scavenging activity of 5-ASA may be a
      major path of pharmacological action of SAZ against inflammatory bowel diseases
      (IBD).

PMID- 16298743
TI  - Up-expression of NapA and other oxidative stress proteins is a compensatory
      response to loss of major Helicobacter pylori stress resistance factors.
AB  - Twenty-six Helicobacter pylori targeted mutant strains with deficiencies in
      oxidative stress combating proteins, including 12 double mutant strains were
      analyzed via physiological and proteomic approaches to distinguish the major
      expression changes caused by the mutations. Mutations were introduced into both a
      Mtz(S) and a Mtz(R) strain background. Most of the mutations caused increased
      growth sensitivity of the strains to oxygen, and they all exhibited clear
      compensatory up-expression of oxidative stress resistance proteins enabling
      survival of the bacterium. The most frequent up-expressed oxidative stress
      resistance factor (observed in 16 of the mutants) was the iron-sequestering
      protein NapA, linking iron sequestration with oxidative stress resistance. The up
      expression of individual proteins in mutants ranged from 2 to 10 fold that of the
      wild type strain, even when incubated in a low O(2) environment. For example, a
      considerably higher level of catalase expression (4 fold of that in the wild-type
      strain) was observed in ahpC napA and ahpC sodB double mutants. A Fur mutant up
      expressed ferritin (Pfr) protein 20-fold. In some mutant strains the bacterial
      DNA is protected from oxidative stress damage apparently via overexpression of
      oxidative stress-combating proteins such as NapA, catalase or MdaB (an NADPH
      quinone reductase). Our results show that H. pylori has a variety of ways to
      compensate for loss of major oxidative stress combating factors.

PMID- 16298744
TI  - Oxidative stress defense mechanisms to counter iron-promoted DNA damage in
      Helicobacter pylori.
AB  - Iron, a key element in Fenton chemistry, causes oxygen-related toxicity to cells
      of most living organisms. Helicobacter pylori is a microaerophilic bacterium that
      infects human gastric mucosa and causes a series of gastric diseases. Exposure of
      H. pylori cells to air for 2 h elevated the level of free iron by about 4-fold as
      measured by electron paramagnetic resonance spectroscopy. H. pylori cells
      accumulated more free iron as they approached stationary phase growth, and they
      concomitantly suffered more DNA damage as indicated by DNA fragmentation
      analysis. Relationships between the intracellular free iron level, specific
      oxidative stress enzymes, and DNA damage were identified, and new roles for three
      oxidative stress-combating enzymes in H. pylori are proposed. Mutant cells
      defective in either catalase (KatA), in superoxide dismutase (SodB) or in alkyl
      hydroperoxide reductase (AhpC) were more sensitive to oxidative stress
      conditions; and they accumulated more free (toxic) iron; and they suffered more
      DNA fragmentation compared to wild type cells. A significant proportion of cells
      of sodB, ahpC, or katA mutant strains developed into the stress-induced coccoid
      form or lysed; they also contained significantly higher amounts of 8-oxo-guanine
      associated with their DNA, compared to wild type cells.

PMID- 16298745
TI  - Copper- and magnesium protoporphyrin complexes inhibit oxidative modification of
      LDL induced by hemin, transition metal ions and tyrosyl radicals.
AB  - The oxidative modification of LDL may play an important role in the early events
      of atherogenesis. Thus the identification of antioxidative compounds may be of
      therapeutic and prophylactic importance regarding cardiovascular disease. Copper
      chlorophyllin (Cu-CHL), a Cu(2+)-protoporphyrin IX complex, has been reported to
      inhibit lipid oxidation in biological membranes and liposomes. Hemin (Fe(3+)
      protoporphyrin IX) has been shown to bind to LDL thereby inducing lipid
      peroxidation. As Cu-CHL has a similar structure as hemin, one may assume that Cu
      CHL may compete with the hemin action on LDL. Therefore, in the present study Cu
      CHL and the related compound magnesium-chlorophyllin (Mg-CHL) were examined in
      their ability to inhibit LDL oxidation initiated by hemin and other LDL oxidizing
      systems. LDL oxidation by hemin in presence of H(2)O(2) was strongly inhibited by
      both CHLs. Both chlorophyllins were also capable of effectively inhibiting LDL
      oxidation initiated by transition metal ions (Cu(2+)), human umbilical vein
      endothelial cells (HUVEC) and tyrosyl radicals generated by myeloperoxidase (MPO)
      in presence of H(2)O(2) and tyrosine. Cu- and Mg-CHL showed radical scavenging
      ability as demonstrated by the diphenylpicrylhydracylradical (DPPH)-radical assay
      and estimation of phenoxyl radical generated diphenyl (dityrosine) formation. As
      assessed by ultracentrifugation the chlorophyllins were found to bind to LDL (and
      HDL) in serum. The present study shows that copper chlorophyllin (Cu-CHL) and its
      magnesium analog could act as potent antagonists of atherogenic LDL modification
      induced by various oxidative stimuli. As inhibitory effects of the CHLs were
      found at concentrations as low as 1 mumol/l, which can be achieved in humans, the
      results may be physiologically/therapeutically relevant.

PMID- 16298746
TI  - Glucose-induced regulation of novel iron transporters in vascular endothelial
      cell dysfunction.
AB  - Increased iron indices have been associated with the development of diabetes and
      its complications. In the present study, we have investigated the glucose-induced
      alteration of iron transporters, divalent metal transporter-1 (DMT-1), iron
      regulated transporter protein-1 (IREG-1), and transferrin receptor (TfR), in
      endothelial cell iron accumulation and oxidative stress. Cells were exposed to
      high glucose levels and subjected to gene expression, protein expression, iron
      measurement and assessment of oxidative stress. Our results show, for the first
      time, expression of DMT-1 and IREG-1 in vascular endothelial cells. Our data
      further indicates upregulation of DMT-1 and IREG-1 mRNA and protein in response
      to high levels of glucose. TfR, however, exhibited a modest decrease in response
      to high levels of glucose. Increased expression of DMT-1 and IREG-1 was
      associated with iron accumulation and oxidative stress. Furthermore, our results
      show differential expression of iron transporters with treatment of high glucose
      exposed cells with two different iron chelators. In conclusion, our study
      suggests that glucose-induced alteration of iron transporters may arbitrate iron
      accumulation and oxidative stress in endothelial cells.

PMID- 16298747
TI  - Vulnerability of the mid aged rat myocardium to the age-induced oxidative stress:
      influence of exercise training on antioxidant defense system.
AB  - This study investigated the onset of age-related changes in the myocardial
      antioxidant defense system (ADS) and the vulnerability of the myocardium to
      oxidative stress following exercise training. Few studies have investigated the
      influence of the most prevalent life-prolonging strategy physical exercise, on
      the age-dependent alterations in the myocardial antioxidant enzyme system of
      female rats at mid age and to determine whether exercise-induced ADS could
      attenuate lipid peroxidation. Two age groups young (3 months old) and mid age (12
      months old) Wistar strain female albino rats were given chronic exercise training
      for a period of 12 weeks. We found a striking decrease (p < 0.01) in the activity
      levels of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase
      (GR) in the myocardium of mid aged rats when compared to young rats by 36, 50 and
      29%, respectively, suggesting the onset of age-dependent decrease in the
      myocardial ADS. A similar age-related decrease (p < 0.01) was observed in the
      reduced glutathione (GSH) content (36%). Despite the reduction in ADS, lipid
      peroxidation (LPO) (20%) was also decreased. In contrast, exercise training
      significantly elevated (p < 0.01) these antioxidant enzyme activities and the
      content of GSH. The increase in SOD and CAT activities were more pronounced in
      the mid aged rats when compared to younger rats, but increased the level of lipid
      peroxidation to higher levels in the mid-age group following the training
      regimen. The findings of the present study suggest that, although the activity
      levels of the myocardial antioxidant enzymes were elevated with the 12 weeks of
      exercise training, the changes were not sufficient enough in attenuating
      oxidative stress in the myocardium of female rats during this short period of
      exercise training.

PMID- 16298748
TI  - Effect of resistance exercise and carbohydrate ingestion on oxidative stress.
AB  - Some research studies have produced data indicating that resistance exercise
      induces oxidative stress, despite minimal increases in VO(2). These studies have
      primarily relied on oxidative stress markers with low sensitivity and debatable
      reliability. However, F(2)-isoprostanes as measured by gas chromatography mass
      spectrometry are considered to be a reliable and precise indicator of oxidative
      stress. Carbohydrate ingestion during exercise is associated with reduced levels
      of stress hormones, which may influence oxidative stress and plasma antioxidant
      potential. Therefore, the purpose of this study was to investigate the influence
      of carbohydrate ingestion during resistance training on F(2)-isoprostanes and
      plasma antioxidant potential. Thirty strength-trained subjects were randomized to
      carbohydrate (CHO) or placebo (PLA) groups that lifted weights for 2 h. Subjects
      received 10 ml kg(- 1) h(- 1) CHO (6%) or PLA beverages during the exercise.
      Blood and vastus lateralis muscle biopsy samples were collected before and after
      exercise and analyzed for cortisol as a marker of general stress, F(2)
      isoprostanes as a measure of oxidative stress, and ferric reducing ability of
      plasma (FRAP) as a measure of antioxidant potential, and for muscle glycogen,
      respectively. Decreases in muscle glycogen content did not differ between CHO and
      PLA. Cortisol and FRAP increased significantly in CHO and PLA (P = 0.008 and
      0.044, respectively), but the pattern of change was not different between groups.
      F(2)-isoprostanes were unaffected by exercise. These results indicate that
      exhaustive resistance exercise and carbohydrate ingestion have no effect on
      oxidative stress or plasma antioxidant potential in trained subjects.

PMID- 16298749
TI  - Aluminum ions stimulate the oxidizability of low density lipoprotein by Fe2+:
      implication in hemodialysis mediated atherogenic LDL modification.
AB  - OBJECTIVE: Al(3+) stimulates Fe(2+) induced lipid oxidation in liposomal and
      cellular systems. Low-density lipoprotein (LDL) oxidation may render the particle
      atherogenic. As elevated levels of Al(3+) and increased lipid oxidation of LDL
      are found in sera of hemodialysis patients, we investigated the influence of
      Al(3+) on LDL oxidation. MATERIALS AND METHODS: Using different LDL modifying
      systems (Fe(2+), Cu(2+), free radical generating compounds, human endothelial
      cells, hemin/H(2)O(2) and HOCl), the influence of Al(3+) on LDL lipid and
      apoprotein alteration was investigated by altered electrophoretic mobility, lipid
      hydroperoxide-, conjugated diene- and TBARS formation. RESULTS: Al(3+) could
      stimulate the oxidizability of LDL by Fe(2+), but not in the other systems
      tested. Al(3+) and Fe(2+) were found to bind to LDL and Al(3+)could compete with
      Fe(2+) binding to the lipoprotein. Fluorescence polarization data indicated that
      Al(3+) does not affect the phospholipid compartment of LDL. CONCLUSIONS: The
      results indicate that increased LDL oxidation by Fe(2+) in presence of Al(3+)
      might be due to blockage of Fe(2+) binding sites on LDL making more free Fe(2+)
      available for lipid oxidation.

PMID- 16298750
TI  - Iron prevents ascorbic acid (vitamin C) induced hydrogen peroxide accumulation in
      copper contaminated drinking water.
AB  - Ascorbic acid (vitamin C) induced hydrogen peroxide (H(2)O(2)) formation was
      measured in household drinking water and metal supplemented Milli-Q water by
      using the FOX assay. Here we show that ascorbic acid readily induces H(2)O(2)
      formation in Cu(II) supplemented Milli-Q water and poorly buffered household
      drinking water. In contrast to Cu(II), iron was not capable to support ascorbic
      acid induced H(2)O(2) formation during acidic conditions (pH: 3.5-5). In 12 out
      of the 48 drinking water samples incubated with 2 mM ascorbic acid, the H(2)O(2)
      concentration exceeded 400 microM. However, when trace amounts of Fe(III) (0.2
      mg/l) was present during incubation, the ascorbic acid/Cu(II)-induced H(2)O(2)
      accumulation was totally blocked. Of the other common divalent or trivalent metal
      ions tested, that are normally present in drinking water (calcium, magnesium,
      zinc, cobalt, manganese or aluminum), only calcium and magnesium displayed a
      modest inhibitory activity on the ascorbic acid/Cu(II)-induced H(2)O(2)
      formation. Oxalic acid, one of the degradation products from ascorbic acid, was
      confirmed to actively participate in the iron induced degradation of H(2)O(2).
      Ascorbic acid/Cu(II)-induced H(2)O(2) formation during acidic conditions, as
      demonstrated here in poorly buffered drinking water, could be of importance in
      host defense against bacterial infections. In addition, our findings might
      explain the mechanism for the protective effect of iron against vitamin C induced
      cell toxicity.

PMID- 16298751
TI  - Effect of daily fruit ingestion on angiotensin converting enzyme activity, blood
      pressure, and oxidative stress in chronic smokers.
AB  - OBJECTIVE: This study examined whether, daily fruit (blueberries) consumption
      (250 g) for three weeks or acute fruit ingestion (250 g) would attenuate
      angiotensin converting enzyme (ACE) activity and reduce oxidative stress in
      chronic cigarette smokers. METHODS: Twenty subjects were recruited and randomized
      into fruit or control groups. Blood samples and blood pressure were obtained at
      baseline and then pre and one hour post when subjects returned to the lab three
      weeks later. To examine acute effects, the fruit group immediately ingested 250 g
      of blueberries after returning and at least one hour prior to the post blood
      draw. Plasma samples were analyzed for ACE activity, F(2)- isoprostanes and lipid
      hydroperoxides (LH) as measures of oxidative stress, and ferric reducing ability
      of plasma (FRAP) as a measure of antioxidant potential. A 2 (treatment) x 3
      (time) repeated measures ANOVA was used for statistical analysis. If interaction
      was significant, then Student's t-tests were used to further examine this
      relationship. For these comparisons, a Bonferroni adjustment was made with
      statistical significance set at P < 0.025. RESULTS: The pattern of change between
      treatments was not significant for any variable except LH (P < 0.001).
      CONCLUSION: This study indicates that LH are significantly reduced by daily fruit
      consumption, but not affected by acute ingestion. This finding could be one way
      in which fruit consumption contributes to prevention of cardiovascular disease.

PMID- 16298752
TI  - Essential requirement of reduced glutathione (GSH) for the anti-oxidant effect of
      the flavonoid quercetin.
AB  - We have analyzed the anti- or pro-oxidant effects of the flavonoid quercetin (QU)
      by evaluating, in U937 cell line, hydrogen peroxide (H(2)O(2)), superoxide anion
      reduced glutathione (GSH) content, mitochondrial membrane potential, DNA content,
      phosphatidylserine exposure on the outer face of the plasma membrane and cell
      viability. Polychromatic flow cytometry was used to evaluate in the same cells
      several functional parameters. For short periods of treatment QU exerted an anti
      oxidant effect (decrease in H(2)O(2) levels), whereas for long periods it showed
      a pro-oxidant activity (increase in ). In these conditions, GSH content was
      reduced, and this correlated with a lack of anti-oxidant activity of QU, which in
      turn could be correlated with proapoptotic activity of this molecule. Thus, QU
      can exert different effects (anti-/prooxidant) depending on exposure times and
      oxidative balance, and in particular on stores of GSH.

PMID- 16298755
TI  - Radical trapping properties of imidazolyl nitrones.
AB  - The ability of ten imidazolyl nitrones to directly scavenge free radicals (R(*))
      generated in polar ((*)OH, O(*)(2)(-), SO(*)(3)(-) cysteinyl, (*)CH(3)) or in
      apolar (CH(3)-(*)CH-CH(3)) media has been studied. When oxygen or sulfur-centered
      radicals are generated in polar media, EPR spectra are not or weakly observed
      with simple spectral features. Strong line intensities and more complicated
      spectra are observed with the isopropyl radical generated in an apolar medium.
      Intermediate results are obtained with (*)CH(3) generated in a polar medium. EPR
      demonstrates the ability of these nitrones to trap radicals to the nitrone
      C(alpha) atom (alpha radical adduct) and to the imidazol C(5) atom (5-radical
      adduct). Beside the nucleophilic addition of the radical to the C(alpha) atom,
      the EPR studies suggest a two-step mechanism for the overall reaction of R(*)
      attacking the imidazol core. The two steps seem to occur very fast with the (*)OH
      radical obtained in a polar medium and slower with the isopropyl radical prepared
      in benzene. In conclusion, imidazolyl nitrones present a high capacity to trap
      and stabilize carbon-centered radicals.

PMID- 16298754
TI  - Dimerisation of N-acetyl-L-tyrosine ethyl ester and Abeta peptides via formation
      of dityrosine.
AB  - Alzheimer's disease (AD) is characterised by the formation of amyloid deposits
      composed primarily of the amyloid beta-peptide (Abeta). This peptide has been
      shown to bind redox active metals ions such as copper and iron, leading to the
      production of reactive oxygen species (ROS) and formation of hydrogen peroxide
      (H(2)O(2)). The generation of H(2)O(2) has been linked with Abeta neurotoxicity
      and neurodegeneration in AD. Because of the relative stability of a tyrosyl
      radical, the tyrosine residue (Tyr-10) is believed to be critical to the
      neurotoxicity of Abeta. This residue has also been shown to be important to Abeta
      aggregation and amyloid formation. It is possible that the formation of an Abeta
      tyrosyl radical leads to increased aggregation via the formation of dityrosine as
      an early aggregation step, which is supported by the identification of dityrosine
      in amyloid plaque. The role of dityrosine formation in Abeta aggregation and
      neurotoxicity is as yet undetermined, partly because there are no facile methods
      for the synthesis of Abeta dimers containing dityrosine. Here we report the use
      of horseradish peroxidase and H(2)O(2) to dimerise N-acetyl-L-tyrosine ethyl
      ester and apply the optimised conditions for dityrosine formation to fully
      unprotected Abeta peptides. We also report a simple fluorescent plate reader
      method for monitoring Abeta dimerisation via dityrosine formation.

PMID- 16298753
TI  - Studies on the protective role of vitamin C and E against polychlorinated
      biphenyl (Aroclor 1254)--induced oxidative damage in Leydig cells.
AB  - Free radical production and lipid peroxidation are potentially important
      mediators in testicular physiology and toxicology. Polychlorinated biphenyls
      (PCBs) are global environmental contaminants that cause disruption of the
      endocrine system in human and animals. The present study was conducted to
      elucidate the protective role of vitamin C and E against Aroclor 1254-induced
      changes in Leydig cell steroidogenesis and antioxidant system. Adult male rats
      were dosed for 30 days with daily intraperitoneal (ip) injection of 2 mg/kg
      Aroclor or vehicle (corn oil). One group of rats was treated with vitamin C (100
      mg/kg bw/day) while the other group was treated with vitamin E (50 mg/kg bw/day)
      orally, simultaneously with Aroclor 1254 for 30 days. One day after the last
      treatment, animals were euthanized and blood was collected for the assay of serum
      hormones such as luteinizing hormone (LH), thyroid stimulating hormone (TSH),
      prolactin (PRL), triiodothyronine (T(3)), thyroxine (T(4)), testosterone and
      estradiol. Testes were quickly removed and Leydig cells were isolated in aseptic
      condition. Purity of Leydig cells was determined by 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD) staining method. Purified Leydig cells were used for
      quantification of cell surface LH receptors and steroidogenic enzymes such as
      cytochrome P(450) side chain cleavage enzyme (P(450)scc), 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase (17beta- HSD).
      Leydig cellular enzymatic antioxidants superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), gamma-glutamyl
      transpeptidase (gamma-GT), glutathione-S-transferase (GST) and non-enzymatic
      antioxidants such as vitamin C and E were assayed. Lipid peroxidation (LPO) and
      reactive oxygen species (ROS) were also estimated in Leydig cells. Aroclor 1254
      treatment significantly reduced the serum LH, TSH, PRL, T(3), T(4), testosterone
      and estradiol. In addition to this, Leydig cell surface LH receptors, activities
      of the steroidogenic enzymes such as cytochrome P(450)scc, 3beta-HSD, 17beta-HSD,
      antioxidant enzymes SOD, CAT, GPX, GR, gamma-GT, GST and non-enzymatic
      antioxidants such as vitamin C and E were significantly diminished whereas, LPO
      and ROS were markedly elevated. However, the simultaneous administration of
      vitamin C and E in Aroclor 1254 exposed rats resulted a significant restoration
      of all the above-mentioned parameters to the control level. These observations
      suggest that vitamin C and E have ameliorative role against adverse effects of
      PCB on Leydig cell steroidogenesis.

PMID- 16298756
TI  - Chemical structure-dependent gene expression of proteasome subunits via
      regulation of the antioxidant response element.
AB  - Antioxidants possess potent ability to regulate gene expression beyond their
      specific antioxidant activity. Genomic analysis reveals that three phenolic
      antioxidants, probucol, BO-653, and tBHQ, all of which have a phenoxyl group with
      one or two tert-butyl groups at the ortho-position, inhibit both the mRNA and
      protein levels of proteasome alpha-subunits in human endothelial cells. The
      chemical structure required for the gene regulation was studied by using
      derivatives of BO-653 and other antioxidants. It was found that the phenoxyl
      group and tert-butyl group at the ortho-position of the compounds were critical
      for down-regulation of the proteasome gene. Two antioxidant responsive elements
      (AREs) were identified in the promoter region of proteasome alpha subunit 3
      (PSMA3). Results from promoter truncation analysis revealed that the proximal ARE
      region was necessary for the down-regulation of the expression of PSMA3.
      Electrophoretic mobility shift assays revealed that BO-653-mediated induction of
      DNA-binding to an upstream promoter region of PSMA3 containing the ARE motif was
      blocked by antibody against c-Jun but not Nrf2. These results indicate that the
      suppression of the proteasome alpha subunits expression by phenolic antioxidants
      is strictly dependent on both their chemical structure and the ARE consensus
      region in the promoter, which may be negatively regulated by AP-1.

PMID- 16298757
TI  - Radical production and DNA damage induced by carcinogenic 4-hydrazinobenzoic
      acid, an ingredient of mushroom Agaricus bisporus.
AB  - 4-Hydrazinobenzoic acid, an ingredient of mushroom Agaricus bisporus, is
      carcinogenic to rodents. To clarify the mechanism of carcinogenesis, we
      investigated DNA damage by 4-hydrazinobenzoic acid using (32)P-labeled DNA
      fragments obtained from the human p53 and p16 tumor suppressor genes. 4
      Hydrazinobenzoic acid induced Cu(II)-dependent DNA damage especially piperidine
      labile formation at thymine and cytosine residues. Typical hydroxyl radical
      scavengers showed no inhibitory effects on Cu(II)-mediated DNA damage by 4
      hydrazinobenzoic acid. Bathocuproine and catalase inhibited the DNA damage,
      indicating the participation of Cu(I) and H(2)O(2) in the DNA damage. These
      findings suggest that H(2)O(2) generated by the autoxidation of 4
      hydrazinobenzoic acid reacts with Cu(I) to form reactive oxygen species, capable
      of causing DNA damage. Interestingly, catalase did not completely inhibit DNA
      damage caused by a high concentration of 4-hydrazinobenzoic acid (over 50 microM)
      in the presence of Cu(II). 4-Hydrazinobenzoic acid induced piperidine-labile
      sites frequently at adenine and guanine residues in the presence of catalase. 4
      Hydrazinobenzoic acid increased formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine
      (8-oxodG), a characteristic oxidative DNA lesion, in calf thymus DNA, whereas 4
      hydrazinobenzoic acid did not increase the formation of 8-oxodG in the presence
      of catalase. ESR spin-trapping experiments showed that the phenyl radical was
      formed during the reaction of 4-hydrazinobenzoic acid in the presence of Cu(II)
      and catalase. Matrix-assisted laser desorption/ionization time-of-flight mass
      (MALDI-TOF/mass) spectrometry analysis showed that phenyl radical formed adduct
      with adenosine and guanosine. These results suggested that 4-hydrazinobenzoic
      acid induced DNA damage via not only H(2)O(2) production but also phenyl radical
      production. This study suggests that both oxidative DNA damage and DNA adduct
      formation play important roles in the expression of carcinogenesis of 4
      hydrazinobenzoic acid.

PMID- 16298758
TI  - Exogenous N-linoleoyl tyrosine marker as a tool for the characterization of
      cellular oxidative stress in macrophages.
AB  - Oxidative stress and its resultant products continue to attract investigators.
      Numerous endogenous substances have been suggested as potential markers for the
      identification of oxidative stress in tissues and organisms. In this study, we
      present a novel concept whereby an exogenous marker is designed and synthesized
      for the characterization of oxidative stress. The designed marker is constructed
      from tyrosine (Tyr) and linoleic acid (LA), which are attached covalently to form
      N-linoleoyl tyrosine (N-LT). Each of the two components (Tyr and LA) is known to
      be easily oxidized upon exposure to different types of reactive species.
      Combining the two allows their distinction from the endogenous Tyr and LA in the
      tested biological samples. The ability of the N-LT marker to characterize
      oxidative stress in macrophage cell lines was first studied using different types
      of ROS/RNS. N-LT was found to interact with macrophages, binding to the cell
      membrane. Upon treatment of J-774 A.1 macrophages with N-LT (40 microM) and with
      various oxidants; HOCl (0.2, 0.4 mM), copper ions (20 microM), SIN-1 (0.1, 1.0
      mM), specific oxidized N-LT (Ox-N-LT) products were formed, depending on the type
      of oxidant used. Exposing cells to HOCl (0.2 mM) resulted in exclusive attack of
      the LA residue of N-LT, preferentially forming an adduct of HOCl to the LA double
      bond (N-L(HOCl)T, 4.3%). In contrast, when SIN-1 (0.1 mM) was applied as the
      oxidant, the Tyr moiety of N-LT was most reactive, yielding a nitration product
      of the Tyr aromatic ring (N-LT(NO(2)), 1.8%). Similar N-LT oxidation in cell-free
      systems yielded a significantly higher content of Ox-N-LT (10.8% N-L(HOCl)T, 7% N
      LT(NO(2)). The designed marker was then tested with peritoneal macrophages taken
      from atherosclerotic apolipoprotein-deficient (E(0)) mice showing specific and
      selective oxidation of N-LT to yield N-LT-hydroperoxide (1.9% N-L(OOH)T), at
      significantly higher levels than resulted from similar experiments using
      peritoneal macrophages harvested from control BalbC mice (0.0% N-L(OOH)T). In
      contrast, the differences in N-L(epoxy)T level between BalbC and E(0) mice were
      not significant using both types of peritoneal macrophages (E(0) and BalbC),
      suggesting that N-L(OOH)T is characteristic of the atherosclerotic state. Thus,
      we show that the designed marker is sufficiently sensitive to detect oxidative
      stress imposed on cells and cell-free systems and to react selectively with the
      various ROS/RNS induced. Such a marker may be useful for characterizing oxidative
      stress in general, and possibly also in oxidative-stress-associated diseases.

PMID- 16298759
TI  - ATP inhibits hydroxyl radical formation and the inflammatory response of
      stimulated whole blood even under circumstances of severe oxidative stress.
AB  - We recently reported that Adenosine-5'-triphosphate (ATP) is able to inhibit the
      inflammatory reaction in stimulated whole blood. Many diseases, in which
      inflammatory reactions are involved, are associated with oxidative stress. In the
      present study, we therefore, investigated the effect of ATP on cytokine release
      in stimulated whole blood under conditions of oxidative stress, as simulated by
      pre-incubation of blood with hydrogen peroxide (H(2)O(2)). In the presence of
      H(2)O(2), ATP at concentrations of 100 and 300 microM inhibited Tumour Necrosis
      factor-alpha (TNF-alpha) release and stimulated IL-10 release in LPS-PHA
      stimulated whole blood. Moreover, electron spin resonance (ESR) measurements
      showed that ATP and its breakdown product Adenosine-5'-diphosphate (ADP)
      attenuated spin trap-hydroxyl radical adduct formation in the Fenton reaction.
      Our results demonstrate that even in circumstances of severe oxidative stress,
      ATP has marked anti-inflammatory properties in stimulated whole blood. Moreover,
      the inhibition of the hydroxyl radical ESR signal indicates a direct attenuation
      of oxidative stress by ATP.

PMID- 16298760
TI  - Hydrazyl-nitrones, novel hybrid molecules in free radical research.
AB  - This work describes the synthesis and characterisation of some novel hybrid
      molecules which contains in the same molecule a free radical moiety of hydrazyl
      type and a spin-trap moiety of nitrone type. The new compounds synthesized have
      multiple and easy to follow spectroscopic properties, making them useful as
      sensors or probes in radical chemistry. The new class of hydrazyl-nitrone
      molecules can act, in a single step process, as both generator and spin-trap of
      short-lived radicals. The hybrid molecules can be also involved in acid-base or
      redox processes, and the chemical processes can be easily monitored by visible or
      electron paramagnetic resonance spectroscopy. The excellent generator and trap
      properties recommend them as valuable sensors and probes in radical chemistry.

PMID- 16298761
TI  - Non-oxygen-forming pathways of hydrogen peroxide degradation by bovine liver
      catalase at low hydrogen peroxide fluxes.
AB  - Heme catalases are considered to degrade two molecules of H(2)O(2) to two
      molecules of H(2)O and one molecule of O(2) employing the catalatic cycle. We
      here studied the catalytic behaviour of bovine liver catalase at low fluxes of
      H(2)O(2) (relative to catalase concentration), adjusted by H(2)O(2)-generating
      systems. At a ratio of a H(2)O(2) flux (given in microM/min(- 1)) to catalase
      concentration (given in microM) of 10 min(- 1) and above, H(2)O(2) degradation
      occurred via the catalatic cycle. At lower ratios, however, H(2)O(2) degradation
      proceeded with increasingly diminished production of O(2). At a ratio of 1 min(-
      1), O(2) formation could no longer be observed, although the enzyme still
      degraded H(2)O(2). These results strongly suggest that at low physiological
      H(2)O(2) fluxes H(2)O(2) is preferentially metabolised reductively to H(2)O,
      without release of O(2). The pathways involved in the reductive metabolism of
      H(2)O(2) are presumably those previously reported as inactivation and
      reactivation pathways. They start from compound I and are operative at low and
      high H(2)O(2) fluxes but kinetically outcompete the reaction of compound I with
      H(2)O(2) at low H(2)O(2) production rates. In the absence of NADPH, the reducing
      equivalents for the reductive metabolism of H(2)O(2) are most likely provided by
      the protein moiety of the enzyme. In the presence of NADPH, they are at least in
      part provided by the coenzyme.

PMID- 16298762
TI  - alpha-Lipoic acid and N-acetyl cysteine prevent zinc deficiency-induced
      activation of NF-kappaB and AP-1 transcription factors in human neuroblastoma IMR
      32 cells.
AB  - This work investigated the capacity of alpha-lipoic acid (LA) and N-acetyl-L
      cysteine (NAC) to reduce zinc deficiency-induced oxidative stress, and prevent
      the activation of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP
      1), and the cross-talk between both activated cascades through beta-Transducin
      Repeat-containing Protein (beta-TrCP). IMR-32 cells were incubated in control
      media or media containing variable concentrations of zinc, without or with 0.5 mM
      LA or 1 mM NAC. Relative to control and zinc supplemented (15 microM Zn) groups,
      Hydrogen peroxide (H(2)O(2)) and total oxidant cell concentrations were higher,
      and total glutathione concentrations were lower in the zinc deficient groups (1.5
      and 5 microM Zn). Both, LA and NAC, markedly reduced the increase in cell
      oxidants and the reduction in glutathione concentrations in the zinc deficient
      cells. Consistent with this, LA and NAC prevented zinc deficiency-induced
      activation of the early steps of NF- kappaB (IkappaBalpha phosphorylation) and AP
      1 [c-Jun-N-terminal kinase (JNK) and p38 phophorylation] cascades, and the high
      NF-kappaB- and AP-1-DNA binding activities in total cell extracts. Thus, LA and
      NAC can reduce the oxidative stress associated with zinc deficiency and the
      subsequent triggering of NF-kappaB- and AP-1-activation in neuronal cells.

PMID- 16298763
TI  - Comparative effects of enzogenol and vitamin C supplementation versus vitamin C
      alone on endothelial function and biochemical markers of oxidative stress and
      inflammation in chronic smokers.
AB  - Chronic smoking is associated with endothelial dysfunction and inflammation, with
      oxidative stress contributing to both these processes. In this study, we
      investigated the effect of combined antioxidant treatment with Enzogenol, a
      flavonoid extract from the bark of Pinus radiata and vitamin C, over and above
      vitamin C alone, on endothelial function, plasma markers of inflammation and
      oxidative stress, blood pressure (BP) and anthropometrics. Forty-four chronic
      smokers without established cardiovascular disease were assigned randomly to
      receive either 480 mg Enzogenol and 60 mg vitamin C, or 60 mg vitamin C alone
      daily for 12 weeks. Endothelial function in the brachial artery was assessed by
      flow-mediated vasodilation (FMD). FMD improved in both treatment groups (p <
      0.001), with no significant difference between the two groups (p = 0.84). In the
      group receiving Enzogenol and vitamin C, protein carbonyl levels were
      significantly reduced compared to the group taking vitamin C alone (p = 0.03).
      Enzogenol and vitamin C resulted in a significant reduction in fibrinogen levels
      in heavy smokers compared with vitamin C alone (p < 0.009). These findings
      demonstrated that co-supplementation with Enzogenol and vitamin C in smokers
      conferred no additional beneficial effect on macrovascular endothelial function
      over and above that seen in the vitamin C alone group. However, Enzogenol did
      demonstrate additional favourable effects on protein oxidative damage and
      fibrinogen levels.

PMID- 16298764
TI  - Quercetin protects C6 glial cells from oxidative stress induced by tertiary
      butylhydroperoxide.
AB  - The anti-oxidant and cyto-protective activity of quercetin against tertiary
      butylhydroperoxide (t-BOOH) induced oxidative stress on C6 glial cells is
      reported. Exposure of the cells to t-BOOH resulted in a significant increase in
      cytotoxicity, reactive oxygen species (ROS) generation and lipid peroxidation.
      There was a significant increase in DNA strand breaks and fall in reduced GSH
      levels in cells exposed to t-BOOH. A significant increase in calcium ion influx
      was noticed in cells exposed to t-BOOH. Pre-treatment of cells with quercetin,
      vitamin C (vit C), Trolox, and deferoxamine (DFO) significantly inhibited t-BOOH
      induced cytotoxicity and ROS generation. Pretreatment of cells with quercetin,
      Trolox and DFO inhibited the DNA damage, maintained higher GSH levels and
      prevented calcium influx significantly. Although vit C protected the cells from
      cytotoxicity induced by t-BOOH, the intracellular Ca(2+) levels were
      significantly higher than the control cells. However, anti-oxidants like
      butylated hydroxy toluene (BHT), vitamin E (vit E), N-acetyl cysteine (NAC) did
      not have significant cytoprotection against t-BOOH induced oxidative injury in C6
      glial cells.

PMID- 16298767
TI  - Natural twilight phase-response curves for the cave-dwelling bat, Hipposideros
      speoris.
AB  - Phase-response curves (PRCs) for the circadian rhythm of flight activity of the
      microchiropteran bat (Hipposideros speoris) were determined in a cave, employing
      discrete natural dawn and dusk twilight pulses. These PRCs are reported for the
      first time for any circadian system and they are unlike other PRCs constructed
      for nocturnal mammals. Dawn and dusk twilight pulses evoked advance and delay
      phase shifts, respectively. Advance phase shifts were followed by 3 to 4
      advancing transients and a subsequent shortening of free-running period (tau);
      whereas, the delay phase shifts were instantaneous without any transients but
      with a subsequent lengthening of tau.

PMID- 16298768
TI  - Differential responses of the photoperiodic clock in two passerine birds
      possessing a strongly self-sustained circadian system.
AB  - To investigate whether the photoperiodic clocks of species possessing strongly
      self-sustaining circadian clocks share identical features, we compared the full
      response cycle (initiation and termination of the response) in body mass and
      testes of the non-migratory house sparrow (Passer domesticus) with that of the
      migratory redheaded bunting (Emberiza bruniceps) under Nanda-Hamner experiments.
      Birds were exposed to a 36 h day (L:D=6:30 h), controls exposed to a 24 h day
      (L:D=6:18 h), for a period of 31 weeks. By week 18 of L:D=6:18 h, there was a
      small increase in body mass among sparrows, but not among buntings, and the
      testes of bunting did not grow, while those of sparrow grew slightly. The
      response to L:D=6:30 h is of particular interest. There was a rapid gain and
      subsequent loss in the body mass of bunting, but not of sparrows. Further, both
      species underwent a testicular cycle as if they were exposed to long days, but
      the response of sparrows was slower and hence delayed the attainment of peak
      testicular size. Such a differential response to exotic light cycles between
      these two photosensitive species, despite their similar circadian oscillatory
      properties (strong self-sustainment), could suggest a species-specific adaptation
      of the endogenous clock involved in photoperiodic regulation of avian
      seasonality.

PMID- 16298765
TI  - Attenuation of intestinal ischemia/reperfusion induced liver and lung injury by
      intraperitoneal administration of (-)-epigallocatechin-3-gallate.
AB  - The aim of this study was to evaluate the effect of ( - )-epigallocatechin-3
      gallate (EGCG), a natural antioxidant, on liver and lungs after warm intestinal
      ischemia/reperfusion (I/R). Thirty male Wistar rats were equally divided into a
      sham-operation group, an intestinal I/R group and an intestinal I/R group
      pretreated with EGCG intraperitoneally. Intestinal ischemia was induced by
      occlusion of the superior mesenteric artery for 60 min followed by reperfusion
      for 120 min. Immediately after reperfusion, liver, lung and blood samples were
      collected and analyzed. Results showed that intestinal I/R increased the levels
      of aspartate (AST) and alanine (ALT) transaminase in serum to 987 and 752 IU/l,
      respectively. Malondialdehyde (MDA) increased in liver to 1.524 nmol/g in the
      group subjected to intestinal I/R compared to 0.995 nmol/g in the sham operation
      group. MDA was also increased in lungs to 1.581 nmol/g compared to 0.896 nmol/g
      in the sham operation group. Myeloperoxidase (MPO) increased in liver, after
      intestinal I/R, to 5.16 U/g compared to 1.59 U/g in the sham operation group. MPO
      was also increased in lungs to 3.89 U/g compared to 1.65 U/g in the sham
      operation group. Pretreatment with EGCG decreased serum levels of AST and ALT to
      236 and 178 IU/l, respectively. It also decreased mean MDA levels in liver and
      lungs to 1.061 and 1.008 nmol/g, respectively, and mean MPO levels in liver and
      lungs to 1.88 and 1.71 U/g, respectively. Light microscopy and transmission
      electron microscopy examinations showed significant alteration in liver and lungs
      and protection of liver and lung parenchyma in the animals treated with EGCG.

PMID- 16298769
TI  - Diurnal changes in blood metabolites and their relation to plasma growth hormone
      and time of feeding in mithun heifers (Bos frontalis).
AB  - The aim of the present study was to investigate what, if any, diurnal changes
      occur in blood metabolites in relation to plasma growth hormone (GH) and feeding
      time among mithun (Bos frontalis), a semi-wild ruminant. Blood samples were
      collected at hourly intervals during a 24 h span from 6 mithun heifers (averaging
      2.5 yr of age and averaging 230 kg in weight) that were fed twice a day at 11:00
      and 16:00 h. Samples were assayed for plasma GH and blood metabolites, non
      esterified fatty acids (NEFA), glucose, and alpha-amino nitrogen. The total
      sampling period was divided into a 1) postprandial (after meal) period (period I:
      11:00 to 21:00 h) and 2) interprandial period (period II: 22:00 to 10:00 h) and
      also into night (20:00 to 05:00 h) and day (06:00 to 10:00 h) periods for
      statistical analysis. Plasma glucose and alpha-amino nitrogen levels increased
      (p<0.01), and plasma NEFA and GH decreased (p<0.01) after each meal. No diurnal
      rhythmicity was detected in plasma glucose or alpha-amino nitrogen levels.
      Interestingly, plasma NEFA and GH levels were higher (p<0.01) during the
      interprandial (period II) and night periods, indicating an energy deficit that
      occurred progressively during the interprandial period of nocturnal feed
      deprivation. In twice-daily-fed mithuns we conclude that: 1) plasma metabolites
      and GH exhibited a definite pattern of change with time of feeding; 2)
      concentrations of plasma NEFA were higher nocturnally due to an energy deficit
      and that GH levels were higher during the interprandial period after the second
      meal; 3) the interprandial period after the second feeding may be considered to
      constitute a short-term food deprivation; 4) the longer interprandial period of
      19 h in this study between the second and subsequent morning meal may be changed
      into equally divided feedings to minimize the short-term energy deficit; and 5)
      blood sampling for blood metabolites in mithuns should be conducted at a fixed
      time of day with special emphasis on time of feeding.

PMID- 16298770
TI  - Daily rhythms of serum leptin in ewes: effects of feeding, pregnancy and
      lactation.
AB  - The aim of the present study was to test whether serum concentrations of leptin
      in ewes vary with a daily rhythm. For this purpose, we examined 24 h serum leptin
      profiles of ewes exposed to natural photoperiodic conditions and subjected to two
      different feeding schedules (regular feeding and fasting). The results show for
      the first time the existence of daily rhythm of plasma leptin in regularly fed
      ewes, with a minimum during the light phase and a peak during the dark phase.
      Daily rhythms of serum leptin persisted after 50 h of fasting, although fasting
      shifted the peak of the rhythm to the beginning of the light phase and
      significantly reduced daily leptin production. To gain a better understanding of
      the role of leptin in the temporal organization of physiological events related
      to pregnancy and lactation, we measured serum leptin profiles throughout 24 h in
      ewes either during pregnancy or lactation. Daily leptin rhythms were found to
      persist during pregnancy and lactation, but both physiological conditions altered
      leptin concentrations. Maternal serum leptin concentration rose between early and
      mid pregnancy, then decreased in the late pregnancy and during lactation. Daily
      serum leptin concentration was significantly lower in nonpregnant, nonlactating
      ewes, compared either to lactating or to early pregnant ewes.

PMID- 16298771
TI  - Measuring phase shifts in humans following a simulated time-zone transition:
      agreement between constant routine and purification methods.
AB  - Twelve healthy participants were studied in an Isolation Unit. For the first 7
      (control) days, subjects lived on UK time. Then the clock was advanced by 8 h,
      mimicking an eastward time-zone transition, and for days 8 to 12, participants
      lived on this new local time. Two constant routines (participants were not
      allowed to sleep, were restricted in movement, and ate regular, identical snacks)
      were undertaken, during the control days (days 3 to 4) and at the end of the
      experiment (days 11 to 12). Rectal temperature and activity were measured
      throughout, with activity used to correct the measured temperatures for the
      direct (masking) effects of the sleep-wake cycle. Phase changes of the
      temperature rhythm between the constant routines were assessed by cross
      correlation and cosinor analysis. During days 8 to 10, the measured temperatures
      and those that had been corrected (purified) for masking were assessed by the
      same two methods, and the shifts were extrapolated to predict the values expected
      during the second constant routine. Individuals differed widely in the phase
      shifts of the temperature rhythm, but the correlations between the changes
      measured by constant routines and those estimated by the purification methods
      were high (r=0.771 to 0.903), and the differences between them were not
      significantly different from zero (p>0.24). Phase shifts of the measured (masked)
      temperature rhythm were poorer predictors of the shift obtained from the constant
      routines (r<or=0.605; mean+/-SD of differences>3+/-4.5 h). Limitations of the
      methods due to the variability of results are discussed, but we conclude that the
      mean phase shifts obtained from purified, but not raw, temperature data show
      acceptable agreement with those found using our version of the constant routine.

PMID- 16298772
TI  - Effect of menopause on melatonin and alertness rhythms investigated in constant
      routine conditions.
AB  - Although studies have reported the effects of the menstrual cycle on melatonin
      rhythmicity, none has investigated the effects of menopause on the melatonin
      rhythm. The circadian rhythm in melatonin and its relationship to subjective
      alertness was investigated in pre- and postmenopausal women under constant
      routine conditions (controlled posture, dim lighting, calorie intake,
      temperature, and prolonged wakefulness). Eleven healthy pre-menopausal (42+/-4
      yr) and 10 postmenopausal women (55+/-2 yr) participated in the study. Salivary
      melatonin samples and subjective measures of alertness and sleepiness were
      assessed hourly during the 22 h constant routine protocol. Postmenopausal women
      had a significantly earlier melatonin acrophase (1.1+/-0.5 h clock time in
      decimal h; mean+/-SEM, p<0.05) compared to the pre-menopausal women (2.3+/-0.3
      h). There was no significant difference between melatonin onset and amplitude
      between the pre-menopausal and postmenopausal women. Self-rated alertness
      declined in both study groups as the length of sleep deprivation increased.
      Melatonin onset preceded the onset of self-rated sleepiness in both groups. The
      time interval between melatonin onset and the onset of sleepiness and alertness
      offset was significantly greater in the postmenopausal women compared to the pre
      menopausal women. In conclusion, under controlled experimental conditions the
      timing of the melatonin rhythm was advanced in postmenopausal women altering its
      phase relationship to subjective alertness and sleepiness.

PMID- 16298773
TI  - Morning melatonin has limited benefit as a soporific for daytime sleep after
      night work.
AB  - Exogenous melatonin administration in humans is known to exert both chronobiotic
      (phase shifting) and soporific effects. In a previous study in our lab, young,
      healthy, subjects worked five consecutive simulated night shifts (23:00 to 07:00
      h) and slept during the day (08:30 to 15:30 h). Large phase delays of various
      magnitudes were produced by the study interventions, which included bright light
      exposure during the night shifts, as assessed by the dim light melatonin onset
      (DLMO) before (baseline) and after (final) the five night shifts. Subjects also
      ingested either 1.8 mg sustained-release melatonin or placebo before daytime
      sleep. Although melatonin at this time should delay the circadian clock, this
      previous study found that it did not increase the magnitude of phase delays. To
      determine whether melatonin had a soporific effect, we controlled the various
      magnitudes of phase delay produced by the other study interventions. Melatonin
      (n=18) and placebo (n=18) groups were formed by matching a melatonin participant
      with a placebo participant that had a similar baseline and final DLMO (+/-1 h).
      Sleep log measurements of total sleep time (TST) and actigraphic measurements of
      sleep latency, TST, and three movement indices for the two groups were examined.
      Although melatonin was associated with small improvements in sleep quality and
      quantity, the differences were not statistically significant by analysis of
      variance. However, binomial analysis indicated that melatonin participants were
      more likely to sleep better than their placebo counterparts on some days with
      some measures. It was concluded that, the soporific effect of melatonin is small
      when administered prior to 7 h daytime sleep periods following night shift work.

PMID- 16298774
TI  - An olfactory stimulus modifies nighttime sleep in young men and women.
AB  - Aromatherapy is an anecdotal method for modifying sleep and mood. However,
      whether olfactory exposure to essential oils affects night-time objective sleep
      remains untested. Previous studies also demonstrate superior olfactory abilities
      in women. Therefore, this study investigated the effects of an olfactory stimulus
      on subsequent sleep and assessed gender differences in such effects. Thirty-one
      young healthy sleepers (16 men and 15 women, aged 18 to 30 yr, mean+/-SD, 20.5+/
      2.4 yr) completed 3 consecutive overnight sessions in a sleep laboratory: one
      adaptation, one stimulus, and one control night (the latter 2 nights in
      counterbalanced order). Subjects received an intermittent presentation (first 2
      min of each 10 min interval) of an olfactory (lavender oil) or a control
      (distilled water) stimulus between 23:10 and 23:40 h. Standard polysomnographic
      sleep and self-rated sleepiness and mood data were collected. Lavender increased
      the percentage of deep or slow-wave sleep (SWS) in men and women. All subjects
      reported higher vigor the morning after lavender exposure, corroborating the
      restorative SWS increase. Lavender also increased stage 2 (light) sleep, and
      decreased rapid-eye movement (REM) sleep and the amount of time to reach wake
      after first falling asleep (wake after sleep onset latency) in women, with
      opposite effects in men. Thus, lavender serves as a mild sedative and has
      practical applications as a novel, nonphotic method for promoting deep sleep in
      young men and women and for producing gender-dependent sleep effects.

PMID- 16298775
TI  - Gender differences in polysomnographic sleep in young healthy sleepers.
AB  - Middle-aged and elderly populations exhibit gender differences in
      polysomnographic (PSG) sleep; however, whether young men and women also show such
      differences remains unclear. Thirty-one young healthy sleepers (16 men and 15
      women, aged 18 to 30 yr, mean+/-SD, 20.5+/-2.4 yr) completed 3 consecutive
      overnight sessions in a sleep laboratory, after maintaining a stable sleep-wake
      cycle for 1 wk before study entry. Standard PSG sleep and self-rated sleepiness
      data were collected each night. Across nights, women showed better sleep quality
      than men: they fell asleep faster (shorter sleep onset latency) and had better
      sleep efficiency, with more time asleep and less time awake (all differences
      showed large effect sizes, d=0.98 to 1.12). By contrast, men were sleepier than
      women across nights. Both men and women demonstrated poorer overall sleep quality
      on the first night compared with the subsequent 2 nights of study. We conclude
      young adult healthy sleepers show robust gender differences in PSG sleep, like
      older populations, with better sleep quality in women than in men. These results
      highlight the importance of gender in sleep and circadian rhythm research studies
      employing young subjects and have broader implications for women's health issues
      relating to these topics.

PMID- 16298776
TI  - Lifestyle regularity measured by the social rhythm metric in Parkinson's disease.
AB  - Parkinson's disease (PD) is a chronic progressive motor disorder that may present
      with a spectrum of symptoms and disease severity. Therapy is frequently
      associated with motor fluctuations and dyskinesias; therefore, monitoring of
      motor fluctuations and daily abilities is important for adequate management. The
      Social Rhythm Metric (SRM) is a diary-like questionnaire that quantifies the
      extent to which a person's life is regular vs. irregular on a daily basis with
      respect to event timing. Lifestyle regularity has been assessed by the SRM in
      other clinical situations. The aim of this study was to evaluate lifestyle
      regularity in a population with PD using the SRM and its relationship to clinical
      and therapeutic factors. Twenty-eight consecutive patients with PD and 14 control
      subjects were studied. Severity of motor dysfunction was evaluated with the
      Unified Parkinson's Disease Rating Scale (UPDRS). Depressive symptoms were
      assessed with the Montgomery Asberg Depressive Rating Scale (MADRS), sleep
      quality with the Pittsburgh Sleep Quality Index (PSQI), and subjective daytime
      sleepiness with the Epworth sleepiness scale. Daily lifestyle regularity was
      assessed by the SRM for 2 weeks. Patients with PD had lower SRM scores than
      controls, and those with motor fluctuations had even lower scores (p=0.04).
      Patients with motor fluctuations showed more clinical disability (p=0.01), a
      worse quality of sleep (p=0.02), and more depressive symptoms (p=0.02). SRM
      results were correlated with PSQI values (p=0.016). Our findings show that the
      regularity of daily activities as measured by the SRM is disorganized in patients
      with PD and that this irregularity is related to sleep quality.

PMID- 16298777
TI  - Biological rhythms of biochemical serum parameters in a Brazilian population: a
      three-year study.
AB  - A marked decrease in analytical and post-analytical variability has been achieved
      in clinical laboratories by the use of automated analytical systems. Current
      studies are now focused on the origin of pre-analytical variability, such as that
      due to intra-individual differences and biological rhythms. The objective of this
      work was to evaluate the occurrence of biological rhythms in several biochemical
      serum parameters in a Brazilian population. A retrospective study (1996 to 1998)
      was carried out to collect the test results within the reference intervals of
      adults, from 21 to 50 yr of age (average age of 36 yr) attending the outpatient
      clinics of the Teaching Hospital at the University of Campinas, Sao Paulo,
      Brazil. The reference sample was 52.9% male and 47.1% female and encompassed
      15,036 calcium, 7,478 phosphorus, 53,641 urea, 58,315 creatinine and 6,433 uric
      acid determinations (140,903 in total). Significant annual rhythms were detected
      in serum calcium (p<or=0.001), with maximum and minimum values in fall and
      spring, and in serum creatinine (p<or=0.002), with maximum and minimum values in
      summer and winter. The other parameters did not present significant annual
      rhythmicity. The seasonal rhythms present in the serum concentrations of calcium
      and creatinine observed in this large population study, although of small
      amplitude, should be considered a component of the pre-analytical variation of
      these clinical laboratory tests.

PMID- 16298778
TI  - Therapeutic mechanism in seasonal affective disorder: do fluoxetine and light
      operate through advancing circadian phase?
AB  - In the context of Lewy's phase delay hypothesis, the present study tested whether
      effective treatment of winter Seasonal Affective Disorder (SAD) is mediated by
      advancing of circadian phase. Following a baseline week, 78 outpatients with SAD
      were randomized into 8 weeks of treatment with either fluoxetine and placebo
      light treatment or light treatment and placebo pill. Depression levels were
      measured on the Ham17+7 and the BDI-II, and circadian phase was estimated on the
      basis of daily sleep logs and self-reported morningness-eveningness. Among the 61
      outpatients with complete data, both treatments were associated with significant
      antidepressant effect and phase advance. However, pre- and post-treatment
      comparisons found that the degree of symptom change did not correlate with the
      degree of phase change associated with treatment. The study therefore provides no
      evidence that circadian phase advance mediates the therapeutic mechanism in
      patients with SAD. Findings are discussed in terms of the limitations of the
      circadian measures employed.

PMID- 16298779
TI  - Seasonal pattern of births in patients with optic neuritis.

PMID- 16298781
TI  - Pathological findings in the temporal bone of newborn infants with neonatal
      asphyxia.
AB  - Hypoxia in adults frequently causes damage to the brain, but not the inner ear.
      However, hypoxia in neonates with inadequate blood-inner ear barrier function
      causes damage to the inner ear, leading to hearing loss and equilibration
      disorder. Clinically, asphyxiated neonates sometimes have the complication of
      sensorineural hearing impairment at high frequencies. Many reports suggest that
      this problem is caused by hypoxic encephalopathy. However, it is not clear
      whether inner ear disorders are present. In this report we examined the inner ear
      pathology of four asphyxiated neonates using serial sections of temporal bone.
      The subjects (n=4) were 1-13-day-old neonates with pregnancy periods of 24-36
      weeks. Their fetal growth curves were within the normal range. There was one case
      each of twin pregnancy, placental abruption, placenta previa and meconium
      aspiration syndrome. For the case of severe neonatal asphyxia, damage to the
      inner ear included the degeneration and disappearance of outer hair cells of the
      organ of Corti and edematous changes in the stria vascularis. Degeneration of
      spiral ganglion and vestibular ganglion cells was observed in two of the other
      cases.

PMID- 16298782
TI  - Nitro-L-arginine methyl ester: a potential protector against gentamicin
      ototoxicity.
AB  - The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as
      an otoprotectant against high-frequency hearing loss caused by gentamicin, but
      further studies are needed to confirm this.Aminoglycoside antibiotics are still
      widely used by virtue of their efficacy and low cost. Their ototoxicity is a
      serious health problem and, as their ototoxic mechanism involves the production
      of NO, we need to assess the use of NO inhibitors for the prevention of
      aminoglycoside-induced sensorineural hearing loss. In this experimental study we
      used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle
      ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its
      effect was determined in terms of attenuation of hearing loss, measured by shifts
      in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced
      hearing loss in the high-frequency range, but gave no protection in the middle or
      low frequencies.

PMID- 16298784
TI  - Evidence of T-helper cell 2 cytokine regulation of chronic otitis media with
      effusion.
AB  - Cytokine and cellular patterns of effusions may reflect stages of middle ear
      inflammation. The local interplay between IL-2 and -4 is likely to play a crucial
      role in the switching of inflammation in the chronic stage. The T-helper cell 2
      (Th2) cytokines IL-4, -5 and -13 and the Th2/Th1 cytokine granulocyte-macrophage
      colony-stimulating factor (GM-CSF) regulate the cellular and molecular processes
      of chronic inflammation in the middle ear and therefore the chronic condition of
      otitis media with effusion (OME). Early identification of the cytokine and
      cellular patterns of effusions can be helpful in directing the clinical treatment
      of OME.We hypothesized that IL-2 and the group of Th2 cytokines regulate chronic
      inflammation in the middle ear and chronic OME. Effusions from children with
      persistent OME were analysed to determine the presence of cytokines (the Th1
      cytokine IL-2, the Th2 cytokines IL-4, -5 and -13 and the Th1/Th2 cytokine GM
      CSF), inflammatory cells (CD4+ T cells, eosinophils, macrophages and neutrophils)
      and mucin. Cytokines were evaluated by means of a quantitative "sandwich"-type
      ELISA, inflammatory cells by means of alkaline phosphatase-anti-alkaline
      phosphatase immunocytostaining and mucin by means of a modified periodic acid
      Schiff method based on a slot-blot technique. The cytokine pattern in effusions
      varied from patient to patient. GM-CSF correlated positively and IL-4 inversely
      with IL-2 and the increased level of IL-4 may have had an inhibitory effect on IL
      2. IL-5 and -13 correlated with IL-4. Inflammatory cells correlated with
      cytokines as follows: CD4+ T cells with IL-2 and -4; macrophages and neutrophils
      with GM-CSF; and eosinophils with IL-5. Some cytokine-cellular correlations in
      effusions were reflected at the clinical level. The mucin content of effusions
      correlated with the concentrations of IL-4 (>10 pg/ml) and -13, suggesting
      involvement of IL-4 and -13 in upregulation of the middle ear mucin metabolism.

PMID- 16298785
TI  - Analysis of risk factors for childhood persistent middle ear effusion.
AB  - Although exposure to infectious agents and parental smoking are known to
      influence the overall risk of otitis media, these risk factors do not appear to
      be linked with the tendency to develop chronic otitis media with effusion (COME)
      instead of recurrent acute otitis media (RAOM). The genetic inflammatory response
      type of the child appears to influence the risk of persistent middle ear effusion
      in COME. Two different clinical presentations of childhood otitis media are
      encountered: RAOM; and COME, which is associated with persistent effusion in the
      middle ear. The objective of this study was to assess putative factors that may
      regulate the development of persistent middle ear effusion in COME. In total, 159
      children with RAOM and their parents (n=304), and 55 children with COME and their
      parents (n=110) were evaluated. All the children with COME or RAOM were aged <4
      years. There was no difference in the frequency of attendance at day care outside
      the home, number of siblings or parental smoking between children with RAOM and
      those with COME. The frequency of parental allergy and asthma was lower among
      children with COME than those with RAOM.

PMID- 16298783
TI  - Observation of the morphology and calcium content of vestibular otoconia in rats
      after simulated weightlessness.
AB  - Reduction in bone formation may have been the main reason for the lower calcium
      content of the otoconia after simulated weightlessness in rats. The head-ward
      distribution of blood volume may explain the morphological changes observed in
      the middle and inner ears. To observe morphological changes in the vestibular
      organs and measure the calcium content of otoconia in rats after simulated
      weightlessness. We used a tail suspension model of simulated weightlessness and
      then investigated changes in the vestibular organs using scanning electron
      microscopy and X-ray microanalysis. In comparison to untreated rats, the
      vestibular otoconia of the rats subjected to simulated weightlessness were small,
      irregularly shaped or fissured, and were arranged loosely and out of order. In
      addition, the calcium content of the otoconia was markedly decreased.

PMID- 16298786
TI  - Canalolithiasis of the superior semicircular canal: an anomaly in benign
      paroxysmal vertigo.
AB  - According to the canalolithiasis theory, benign paroxysmal vertigo (BPPV) is
      caused by gravity-dependent movements of otoconial debris that collects in the
      endolymph of the posterior semicircular canal. Other parts of the vestibular
      organ are rarely affected, and it is mainly the horizontal canal that is affected
      by this atypical form of BPPV. Canalolithiasis of the superior semicircular canal
      must be considered an anomaly because the superior semicircular canal is the
      highest point of the vestibular organ and debris normally cannot collect in this
      special location. Until now, BPPV of the superior canal has mainly been dealt
      with theoretically in the literature. The authors present three patients with
      canalolithiasis of the superior semicircular canal and offer direct proof of the
      condition using high-resolution 3D MRI.

PMID- 16298787
TI  - Conservative management versus surgery for small vestibular schwannomas.
AB  - A high rate of deterioration in hearing function and the loss of patient
      compliance during conservative management should be taken into account when
      considering hearing preservation strategies for patients with vestibular
      schwannoma (VS). To compare conservative management with surgery for solitary
      small VS. Among 693 patients followed up for VS between 1991 and 2002, 114 (16%)
      intracanalicular VSs (stage 1) and 302 (44%) VSs measuring <15 mm in the
      cerebellopontine angle (stage 2) were included in this study. Initially, surgery
      was performed in 305 (73%) cases (50 stage 1, 255 stage 2) and 111 (27%) were
      managed conservatively (64 stage 1, 54 stage 2) by means of annual MRI scans and
      audiometry. Conservative management was chosen in patients aged >60 years and in
      those who refused surgery. In this subgroup, the mean follow-up period was 33
      months (range 6-111 months). In the conservative management group, 47% of VSs
      showed significant growth, 47% were stable and 6% showed regression. Seventeen
      patients (15%) were operated on secondarily for tumour growth and 1 (1%) was
      irradiated for tumour growth and because surgery was contraindicated.
      Deterioration of hearing function by > or =1 class was observed in 56% of cases,
      34% of patients were initially in hearing class D and only 10% showed stable
      hearing function. Of the conservative management group, 17% were lost during
      follow-up. After surgery, grade 1 or 2 facial function was obtained in 86% of
      cases. Following hearing preservation attempts (n=137), 54% of patients were in
      hearing classes A-C.

PMID- 16298789
TI  - Distributional characteristics of sulfated glycosaminoglycans in normal human
      nasal mucosa and nasal polyp.
AB  - The results of this study suggest that an altered expression pattern of sulfated
      glycosaminoglycans (GAGs) in nasal polyp may not function as a charge restriction
      barrier for vascular permeability, contributing to the leakage of protein and
      fluid. Sulfated GAGs are found on the vascular endothelial surface and in the
      extracellular matrix in various tissues and organs, suggesting that these
      materials constitute a negatively charged screen restricting the movement of
      circulating plasma molecules. This study was designed to elucidate the
      distributional characteristics of sulfated GAGs in normal human nasal mucosa and
      nasal polyp in order to understand their roles in the formation of nasal polyp.
      The expression and localization of sulfated GAGs in normal human nasal mucosa and
      nasal polyp were detected light microscopically with the histochemical method
      using poly-L-lysine-conjugated colloidal gold followed by silver enhancement.
      Sulfated GAGs in normal human nasal mucosa were distributed in the epithelial
      layer, vascular endothelial surface, submucosal gland and extracellular matrix.
      In nasal polyp, intense staining was also seen in the glandular structure and
      epithelial layer. However, the vascular endothelium and extracellular matrix
      exhibited either a weak reaction or no reaction.

PMID- 16298788
TI  - Comparison between intraoperative observations and electromyographic monitoring
      data for facial nerve outcome after vestibular schwannoma surgery.
AB  - A four-channel device may enhance the sensitivity of electromyography (EMG).
      Determination of stimulation thresholds (STs) below 0.05 mA improves facial
      prognostic information after vestibular schwannoma (VS) surgery. To compare
      intraoperative observations with electromyographic data for predicting the
      immediate facial function outcome after VS surgery.A total of 111 VS patients
      operated on and intraoperatively monitored using four-channel facial EMG between
      October 2002 and September 2003 were included in this multicentre, prospective
      study. Mascular activity detection was performed in the frontal, orbicularis
      oculi, orbicularis oris and platysma muscles. Intraoperative observations were
      made concerning adhesion and nerve stretch, and facial function was graded (House
      Brackmann classification) at postoperative Days 1 and 8.Facial function at
      postoperative Days 1 and 8 was related to the intraoperative nerve STs at the
      brainstem and in the adhesion zone (range 0.01-3 mA for a response > 100 microV).
      At postoperative Day 8, good facial function (Grades 1 or 2) was observed in 93%
      of cases for STs in the adhesion zone of 0.01-0.04 mA, 85% for STs of 0.05-0.3 mA
      and 79% for STs > 0.3 mA. These STs were related to the degree of tumor adhesion
      and not to the nerve stretch. The maximal EMG response was detected in the
      frontal or platysma muscles in 26% of cases, and in the orbicularis oris and
      orbicularis oculi muscles in 74%.

PMID- 16298790
TI  - A comparison between nitric oxide output in the nose and sinuses: A pilot study
      in one volunteer.
AB  - From a study of nitric oxide (NO) output in the nose and sinuses it seems that:
      (i) the results obtained regarding the regulation of NO output in the nose do not
      necessarily apply to the sinuses; (ii) the results obtained for one group of
      sinuses may not apply to another; and (iii) NO output in the sinuses does not
      behave as one would expect if it serves to protect against infection.A pilot
      study was undertaken in one subject to determine whether the control of NO output
      in the nose differs from that in the sinuses.NO output was measured by aspirating
      different gaseous concentrations of oxygen (and/or carbon dioxide) through the
      nasal airways or punctured maxillary and frontal sinuses before and after i.v.
      administration of L-arginine (20 mg/kg). In the absence of gaseous oxygen in the
      nose or maxillary antrum, the effect of L-arginine on NO output was the same as
      that in the presence of oxygen. In the frontal sinus, the effect of L-arginine on
      NO output was blocked by the absence of gaseous oxygen. NO output in the nose and
      frontal sinus showed similar changes after either i.v. administration of L
      arginine or removal of oxygen from the air. NO output in the maxillary antrum was
      virtually unaffected by either procedure. NO output in the nose was largely
      unaffected by the gaseous carbon dioxide content but that in the frontal and
      maxillary sinuses was profoundly inhibited by it. In both sinuses, suppression of
      NO output by carbon dioxide was countered by oxygen. Alterations in the oxygen or
      carbon dioxide content of the maxillary antrum did not alter NO output in the
      frontal sinus, or vice versa. After i.v. infusion of L-arginine, nasal NO output
      remained elevated for >1 h.

PMID- 16298791
TI  - A novel method of measuring gas phase nitric oxide concentration in cell
      cultures.
AB  - This is the first report on the measurement of nitric oxide (NO) concentrations
      in the gas phase in a squamous cell culture. The technique may permit the
      assessment of NO output under conditions that aim to mimic facets of pathology in
      relatively inaccessible tissues. The primary aim of this study was to devise a
      method to detect the NO concentration produced by cell cultures in the gas phase
      of a culture flask. A secondary aim was to determine whether the effect of
      hypoxia or radiation on NO production in a human squamous cell carcinoma cell
      culture would be detectable with this technique. The NO concentration was
      measured off-line using a rapid-response chemiluminescent analyzer. The gas
      samples were aspirated from cell culture flasks (i) under normal culture
      conditions, (ii) under conditions of hypoxia and (iii) following radiation of
      human head and neck squamous cell carcinoma cell line cultures. Elevated levels
      of the gas phase NO concentration were consistently obtained from the cell
      culture flasks using this experimental set-up. Hypoxia and radiation diminished
      NO production.

PMID- 16298793
TI  - Head and neck squamous cell carcinoma spheroid- and monocyte spheroid-stimulated
      IL-6 and monocyte chemotactic protein-1 secretion are related to TNM stage,
      inflammatory state and tumor macrophage density.
AB  - Monocyte fragment (F)-spheroid-stimulated and F-spheroid IL-6 and monocyte
      chemotactic protein (MCP)-1 secretion are related to inflammatory state,
      macrophage density and the TNM stage of patients with head and neck squamous cell
      carcinoma (HNSCC). Fragment (F)-spheroids from HNSCC patients in vitro secrete
      and stimulate autologous monocytes to secrete IL-6 and MCP-1. The aim of this
      investigation was to study this cytokine secretion in relation to other
      cytokines, spheroid composition and host factors.In series I (n=14) the densities
      of epithelial cells, fibroblasts and macrophages were determined in sections from
      F-spheroids and donor tissue. In series II (n=17) the TNM stage, donor
      inflammatory state, macrophage density and the secretion of F-spheroid- and
      monocyte F-spheroid-stimulated IL-6, MCP-1 and tumor necrosis factor (TNF)-alpha
      were determined. Epithelial cells were partly replaced by interstitial tissue
      during spheroid formation. Malignant (M) F-spheroids secreted more MCP-1 than
      benign (B) F-spheroids. No F-spheroid secreted measurable amounts of TNF-alpha.
      Monocytes secreted more IL-6 when co-cultured with MF- compared to BF-spheroids.
      Monocyte IL-6 MF- and MCP-1 MB-spheroid-stimulated secretion correlated with
      macrophage density. In addition, there was an association between MF- and BF
      spheroid-stimulated monocyte cytokine secretion, as well as between BF- and MF
      spheroid-stimulated MCP-1 secretion. An inverse relation was also noted between
      the erythrocyte sedimentation rate at monocyte harvest and the monocyte MCP-1 F
      spheroid responses.

PMID- 16298792
TI  - Lipopolysaccharide decreases connexin 43 expression on nasal epithelial cells in
      vitro.
AB  - Decreased connexin 43 (Cx43) expression as a result of application of
      lipopolysaccharide (LPS) may limit the diffusion of intercellular signaling
      molecules that is essential to the coordinated function of neighboring cells.
      Therefore, it may be related to a ciliary beating defect in nasal epithelial
      cells and result in accumulation of harmful substances.Gap junction intercellular
      communication (GJIC) is altered during inflammation in tracheal epithelial cells.
      Thus, we aimed to investigate whether LPS affects the expression of Cx43, the
      elementary protein composing the gap junction of nasal epithelial cells, in
      vitro.LPS (Pseudomonas aeruginosa serotype 10) was applied to epithelial cells
      obtained from nasal polyp for 24 h in vitro. As an inflammatory indicator, IL-8
      secretion was measured using a commercially available ELISA kit. Cx43 protein was
      detected semi-quantitatively using Western blotting. The nasal epithelial cells
      constitutively secreted IL-8 at a concentration of 0.45+/-0.03 ng/microg protein.
      In the presence of 10(-2) mg/ml LPS, the concentration of IL-8 was significantly
      increased to 0.55+/-0.05 ng/microg protein (n=8). Expression of the Cx43:beta
      actin ratio decreased in a time- and dose-dependent fashion (10(-3)-10(-1) mg/ml
      LPS).

PMID- 16298794
TI  - Wegener's granulomatosis: a challenging disease for otorhinolaryngologists.
AB  - Diagnosis of Wegener's granulomatosis (WG) can be delayed because of its
      aspecific presenting symptoms. Detection of serum circulating antineutrophil
      cytoplasm antibodies (c-ANCAs), in combination with histology, permits one to
      identify WG at an early stage and to implement stage-adapted therapy. c-ANCA
      levels may also help to evaluate the response to medical therapy. Recently, the
      quality of life of WG patients has been improved by administering cotrimoxazole
      in order to prevent infections and recurrent diseases during the remission
      period.WG is of special significance to the otorhinolaryngologist because it is
      often initially limited to the upper respiratory tract before becoming systemic.
      The aim of this paper was to describe a series of WG patients and underline the
      difficulties involved in diagnosing and treating this challenging disease. This
      was a prospective study in 23 consecutive patients with head and neck
      manifestations of WG (17 systemic, 6 limited). Diagnosis was performed by means
      of both c-ANCAs detection using indirect immunofluorescence and histology in
      biopsy specimens. Treatment consisted of daily cyclophosphamide (CYC; 2
      mg/kg/day) and glucocorticoids (prednisone; 1 mg/kg/day). If an improvement or
      toxic events occurred, CYC was discontinued and methotrexate was started. If,
      during remission of the disease, low serum c-ANCAs levels were detected, CYC was
      suspended and cotrimoxazole (1 g/day) was introduced. Serum c-ANCAs detection was
      positive for all patients. Biopsy was diagnostic from the beginning in 19/23
      cases. The six patients with limited WG did not show a progression to systemic
      disease. Only 3 patients with a diagnosis of delayed systemic WG died, whereas
      19/23 patients were alive with good control of relapses.

PMID- 16298795
TI  - Retropharyngeal space and lymph nodes: an anatomical guide for surgical
      dissection.
AB  - Identification of the alar fascia is the key part of surgical dissection of the
      retropharyngeal lymph nodes (RPLNs). In cases where mandibulotomy is not
      performed for the removal of the primary tumor and/or the posterior pharyngeal
      wall is not incised, the medial or lateral approaches described in this paper can
      be performed. Surgical dissection of the RPLNs may improve prognosis and
      locoregional control in oropharyngeal, hypopharyngeal and cervical esophageal
      carcinomas. There have been no previous anatomical studies concerning landmarks
      and approaches for the surgical dissection of the RPLNs. This study was designed
      to illustrate the fascial anatomy of the retropharyngeal region (RPR), provide
      anatomical guidelines for RPLN dissection and describe and compare approaches for
      surgical removal of the RPLNs. Twelve fixed cadavers were used. Slices were
      obtained from the necks of the first three cadavers and the RPRs of the slices
      were dissected under an operating microscope. The other nine cadavers were
      dissected in a surgical position to expose the RPLNs and the fasciae of the RPR.
      In the coronal plane, the alar fascia divides the space between the
      buccopharyngeal and prevertebral fasciae into two compartments and constitutes
      the posterior border of the retropharyngeal space, which contains the RPLNs. The
      alar fascia, an important landmark for reaching the RPLNs, can be identified by
      the cervical sympathetic trunk, superior sympathetic ganglion and superior
      laryngeal nerve. Two approaches can be performed to remove the RPLNs, namely
      medial or lateral to the internal and external carotid arteries, internal jugular
      vein and vagus nerve.

PMID- 16298796
TI  - Displacement of electrodes of a cochlear implant into the vestibular system:
      intra- and postoperative electrophysiological analyses.
AB  - A cochlear implant device is normally inserted into the scala tympani via a
      posterior tympanotomy and cochleostomy. There has been no previous report of
      displacement of the array into the vestibular part of the labyrinth. The authors
      present and discuss the audiological and electrophysiological measurements of a
      case in which part of the array herniated through into the vestibule.

PMID- 16298797
TI  - Sudden deafness as a sign of stroke with normal diffusion-weighted brain MRI.
AB  - Sudden deafness without associated neurological signs and symptoms is typically
      attributed to a viral inflammation of the labyrinth. Sudden deafness as a
      heralding manifestation of basilar occlusion has rarely been described. A 60-year
      old male with hypertension presented with an acute onset of isolated sudden
      deafness with vertigo. On admission, initial brain MRI, including diffusion
      weighted images, was normal. Two days after the onset of symptoms, the patient
      presented with an exacerbation of vertigo. A follow-up MRI scan revealed new
      infarcts involving the right middle cerebellar peduncle, right dorsolateral pons
      and right anterior cerebellum. In this patient, the acute onset of isolated
      sudden deafness with vertigo may have been a heralding manifestation of the
      pontocerebellar infarction.

PMID- 16298798
TI  - Ethmoid osteoma with frontal and orbital extension: endoscopic removal and
      reconstruction.
AB  - Endoscopy provides a safe and effective way of treating craniofacial bony benign
      lesions. This approach permits not only complete removal of the tumour, but also
      reconstruction of the bony boundaries as necessary. Osteoma is a rare, osteogenic
      tumour that usually grows slowly and asymptomatically. It is the most frequent
      benign neoplasm of the nose and paranasal sinuses. Orbital extension is a rare
      event that can give rise to ocular signs and symptoms; in such a case treatment
      is mandatory, although debate persists regarding the optimal approach. We report
      the case of a bulky fronto-ethmo-orbital osteoma that was treated using an
      endoscopic trans-nasal approach. The medial wall of the orbit was repaired by
      means of an implant of porous polyethylene endoscopically positioned using an
      "underlay" technique. The surgical technique is described and the reasons for the
      endoscopic choice are also discussed. Fifteen days after the operation the
      patient reported complete resolution of craniofacial pain. Nasoendoscopy showed
      complete integration of the polyethylene implant in the healing tissue 4 weeks
      after surgery. A CT scan performed 6 months postoperatively showed good
      ventilation of the sinonasal cavity and effective reconstruction of the medial
      orbital wall.

PMID- 16298799
TI  - Monostotic fibrous dysplasia of temporal bone: report of two cases and review of
      its characteristics.
AB  - Fibrous dysplasia is a bone disorder of unknown origin characterized by slow,
      progressive replacement of bone by abnormal proliferative isomorphic fibrous
      tissue. The disease was first described by McCune and Bruch in 1937. Craniofacial
      involvement is found in only 10% of cases of the monostotic variety, while
      temporal bone involvement is rare. We report herein two cases of monostotic
      fibrous dysplasia involving temporal bone and briefly review the clinical
      implications and management of the disease.

PMID- 16298800
TI  - Epiglottitis and necrotizing fasciitis: a life-threatening complication of
      infectious mononucleosis.
AB  - Life-threatening cervical complications associated with infectious mononucleosis
      are rare. The combination of acute epiglottitis and subsequent necrotizing
      fasciitis of the head and neck in a patient with infectious mononucleosis has not
      been reported to date.A 47-year-old female with infectious mononucleosis and
      epiglottitis was admitted to hospital for i.v. therapy. Owing to her poor
      clinical condition and the spread of the infection to the throat and superior
      mediastinum, as evidenced by CT, a cervical debridement was performed. After
      cervical debridement, histological findings were consistent with necrotizing
      fasciitis. The bacteria identified were Streptococcus viridans, Veilonella spp.
      and Capnocytophaga spp. The patient was hospitalized for 33 days.Mononucleosis,
      usually a benign condition, may be associated with life-threatening septic
      complications in the neck and chest. Serial CT or MRI scans are necessary to
      assess the development of the infection in the deep layers of the neck. Rapid
      medical treatment, extensive surgical debridement and intensive care are vital.

PMID- 16298801
TI  - Endoscopic vocal cord medialization: a new surgical technique without neck
      incision for laryngeal palsy.
AB  - Different types of surgery have been reported for glottal insufficiency due to
      unilateral vocal cord paralysis. We recently developed a new surgical technique
      of fascia implantation known as vocal cord medialization. This new method
      achieves a wide glottal gap during phonation, without the use of an external
      approach. This new technique is described in detail herein, together with the
      satisfactory results we obtained in six cases of unilateral vocal cord paralysis
      with a wide glottal gap during phonation. We recommend this technique in cases of
      unilateral vocal cord paralysis in which both a satisfactory clinical result and
      an aesthetically pleasing cosmetic result are required.

PMID- 16298802
TI  - Acutely-dissociated Schwann cells used in tendon autografts for bridging nerve
      defects in rats: a new principle for tissue engineering in nerve reconstruction.
AB  - A new method of acute dissociation of Schwann cells was used to study the effect
      of addition of such cells to a tendon autograft--a recently-described graft
      material--on peripheral nerve regeneration in rats. Autologous Schwann cells were
      obtained from enzymatic dissociation of predegenerated nerves. The tendon
      autografts were supplied with Schwann cells through brief in vitro coincubation.
      Schwann cell-free tendon autografts were used as controls. Axonal outgrowth was
      measured immunohistochemically after four, seven, and 10 days. At seven days,
      outgrowth was significantly longer in the pretreated autografts. The use of
      acutely-dissociated Schwann cells is a new approach to tissue engineering in
      nerve reconstruction, and may abolish the need for time-consuming culture of
      Schwann cells.

PMID- 16298803
TI  - Study of the neovascularisation of prefabrication of flaps using a silicone sheet
      and an isolated arterial pedicle: experimental study in rabbits.
AB  - Use of an isolated artery as an implanted pedicle in prefabricated flaps has
      rarely been reported either clinically or experimentally. In Chinchilla Bastard
      rabbits (n = 36), we dissected an isolated arterial pedicle from the femoral and
      saphenous artery, anastomosed it end-to-end to the femoral vein at the inguinal
      ligament and created an isolated arterial loop pedicle. This was implanted and
      fixed with polyglactin 9/0 under a random-pattern vascularised abdominal
      fasciocutaneous flap. The neovascularisation in the prefabricated flaps was
      evaluated macroscopically, by blood analysis, selective microangiography, and
      histology. The results showed a progressive degree of neovascularisation that
      corresponded to the increasing length of time that the pedicle was implanted in
      the flaps. Twenty days after prefabrication, the abdominal fasciocutaneous flap
      was readily perfused by the blood supply from the arterial pedicle. The capacity
      of the vessels in this group as seen on angiograms had increased to 258 vessels
      (108%) compared with the control group (239 vessels, 100%).

PMID- 16298804
TI  - Use of a skin adhesive (octyl-2-cyanoacrylate) and the optimum reinforcing
      combination for suturing wounds.
AB  - The adhesion strength of a skin adhesive, octyl-2-cyanoacrylate (Dermabond), was
      measured under various conditions using porcine skin. The combined use of a skin
      adhesive and a skin closure tape (n = 5) was significantly stronger than a single
      application of skin adhesive (n = 5) (p < 0.01). We have tentatively named the
      wound closure in which a skin adhesive and reinforcement material were combined
      the Reinforcing Combination Method. To obtain optimum conditions, further studies
      were done for sequence of application, type of reinforcement material, a number
      of layers, and width of the suture. The optimum condition for the reinforcement
      combination was established by applying one layer of skin adhesive over a skin
      closure tape, over one layer of skin adhesive, with a suture width of 4 cm. This
      reinforcement combination might be useful in clinical practice.

PMID- 16298805
TI  - Construction of pigmented skin equivalent and its application to the study of
      congenital disorders of pigmentation.
AB  - We have constructed a pigmented skin equivalent and used it to study the
      hyperpigmentation seen in cafe-au-lait macules to elucidate whether the pigmented
      skin equivalent could be used as a model of congenital hyperpigmentary disorders.
      When we used fibroblasts derived from cafe-au-lait macules of neurofibromatosis
      type 1, the amount of pigment was significantly greater than in models using
      cells derived from normal skin. Quantities of pigment were not seen when
      keratinocytes derived from solitary cafe-au-lait macules were used, a possible
      reason being that keratinocytes on the skin equivalent are in a proliferating
      condition and are not well-differentiated enough to act on other cells. Our
      results suggested that our pigmented skin equivalent is useful for the study of
      congenital hyperpigmentary disorders, although insufficient differentiation of
      keratinocytes might be a disadvantage.

PMID- 16298806
TI  - Correction of the nose in patients with unilateral cleft lip with composite
      grafts.
AB  - We used composite conchal cartilage graft for columellar lengthening in eight
      patients with unilateral cleft lip and a nasal deformity. In 16 patients we used
      a buccal mucosal graft to line the nasal vestibule. We also used corrective
      procedures such as alveolar bone grafting for closure of palatal fistulas,
      septoplasty, malar augmentation, nasal osteotomy, and Le Fort I osteotomy to deal
      with associated deformities. Grafts took well with no loss and no donor site
      morbidity. In the follow up of 8 months-3 years, corrections were found to be
      stable and satisfying to all the patients. Only by replacing deficient tissues
      with similar tissues and putting them in the proper anatomical position can long
      term consistent and reliable results be achieved in the correction of nasal
      deformities associated with unilateral cleft lip.

PMID- 16298807
TI  - Intraoperative application of three-dimensional imaging for breast surgery.
AB  - The planning of an operation based on three-dimensional imaging has been used
      mainly in orthognathic surgery. It is a useful way to plan the preoperative
      treatment as well as to make the postoperative evaluation. We used this technique
      in breast reconstruction. For the evaluation of breast volume and contour, we
      used three-dimensional photography by laser scanner, and these were analysed
      intraoperatively. Three-dimensional data obtained during the operation gave us
      precise information about the volume and contour of the breast.

PMID- 16298808
TI  - Orbitopalpebral repair after 835 excisions of malignant tumours.
AB  - Repair of any defect in the eyelid depends on its size and position and the state
      of the surrounding tissues. Basal cell carcinoma (BCC) is the most common
      malignant tumour of the eyelids, and squamous cell carcinoma (SCC), mixed
      carcinomas or basosquamous cell carcinomas (BSC), and cutaneous melanomas (CM),
      also invade the eyelids and periocular zones. Reconstruction of the eyelids and
      associated orbital structures after resection requires a complete understanding
      of the anatomy. The adequacy of the reconstruction is judged by the quality of
      functional restoration and the aesthetic appearance. The purpose of this study
      was to document various, simple or complex reconstructive procedures that may be
      used after excision of malignant tumours of the eyelids and to assess the outcome
      of surgical treatment.

PMID- 16298809
TI  - Prospective study of patients with injuries to the hand and forearm: costs,
      function, and general health.
AB  - Patients with injured hands and forearms of varying severity [Hand Injury
      Severity Score (HISS)] were studied prospectively, including analysis of costs,
      hand/arm function (DASH), and health status (SF-36). Costs, duration of sick
      leave, DASH-score (high score; impaired function) increased by severity of injury
      (higher HISS) and the greatest proportion of total costs resulted from lost
      production. Most employed patients returned to work within a year, but even minor
      injuries were expensive. HISS and costs of care during an emergency were
      significantly associated with duration of sick-leave, although HISS did not fully
      explain variation in costs and duration of sick-leave. DASH-score at one year was
      associated with variation in age, HISS, and residual health care costs. Results
      of DASH and subgroups for physical and bodily pain on SF-36 were consistent.
      Injuries to hand and forearm may generate high costs for society in terms of
      health care and long periods of sick-leave (lost production), but even minor
      injuries should be accounted for.

PMID- 16298810
TI  - Artificial sensibility of the hand based on cortical audiotactile interaction: a
      study using functional magnetic resonance imaging.
AB  - The capacity of the central nervous system for plastic alterations is the base
      for our ability to adapt to environmental needs. The crossmodal capacity of the
      brain makes interaction between senses possible, and deprivation of one sense
      leads to compensatory changes in other senses. We have recently shown how hearing
      can substitute for sensation in a transplanted insensitive hand by using a sensor
      glove equipped with small microphones that pick up the sound of friction, which
      is elicited by active touch. Here we have used functional magnetic resonance
      imaging (fMRI) in healthy people to illustrate their capacity for cortical
      audiotactile interaction with activation of the somatosensory cortex induced by
      auditory stimuli. The phenomenon occurred only in subjects trained to substitute
      sensibility by hearing, and no audiotactile interaction was found in untrained
      subjects.

PMID- 16298811
TI  - Skin burned by contact with flagstones made of cement.
AB  - Chemical burns account for few admissions to burns units. A well-known but rare
      cause is wet cement. We present a case where a man had a full-thickness skin burn
      after contact with flagstones made of cement.

PMID- 16298812
TI  - Histological evaluation of grafted hard palate mucosa in the reconstruction of
      the upper eyelid.
AB  - We have used a hard palate mucosal graft for reconstruction of the posterior
      lamella of the eyelid and in only one case was replacement required because of
      discomfort and pain. The stratum corneum of the hard palate mucosa may have been
      the cause.

PMID- 16298813
TI  - Osteonecrosis of the metacarpal head in a patient with a prothrombin 20210A gene
      mutation.
AB  - Osteonecrosis of the metacarpal head is rare and of unknown cause. We describe a
      17-year-old girl with osteonecrosis of the fourth metacarpal head and a mutated
      prothrombin 20210A gene, which suggests a possible relation between a
      hypercoagulable state and osteonecrosis of the metacarpal head.

PMID- 16298814
TI  - Standing together: how bioethics and public health can join forces to provide
      equitable health care.

PMID- 16298815
TI  - Paradigms of notch signaling in mammals.
AB  - Notch proteins regulate a broad spectrum of cell fate decisions and
      differentiation processes during fetal and postnatal life. These proteins are
      involved in organogenesis during embryonic development as well as in the
      maintenance of homeostasis of self-renewing systems. The paradigms of Notch
      function, such as stem and progenitor cell maintenance, lineage specification
      mediated by binary cell fate decisions, and induction of terminal
      differentiation, were initially established in invertebrates and subsequently
      confirmed in mammals. Moreover, aberrant Notch signaling is linked to
      tumorigenesis. In this review, we discuss the origin of postulated Notch
      functions, give examples from different mammalian organ systems, and try to
      relate them to the hematopoietic system.

PMID- 16298817
TI  - Deregulated NOTCH signaling in acute T-cell lymphoblastic leukemia/lymphoma: new
      insights, questions, and opportunities.
AB  - Recent work has shown that the majority of human acute T-cell lymphoblastic
      leukemias and lymphomas (T-ALL) have gain-of-function mutations in NOTCH1, a type
      I transmembrane receptor that normally signals through a gamma-secretase
      dependent mechanism that relies on ligand-induced regulated intramembranous
      proteolysis. Cleavage by gamma-secretase releases the intracellular domain of
      NOTCH1 (ICN1), permitting it to translocate to the nucleus and form a short-lived
      transcriptional activation complex that is essential for normal T-cell
      development. Two types of mutations are prevalent in human T-ALL: extracellular
      domain mutations that increase ICN1 production and C-terminal mutations that
      sustain ICN1 action. Inhibitors of ICN1 production and activity abrogate the
      growth of established T-ALL cell lines, and a clinical trial of a NOTCH pathway
      inhibitor in patients with refractory T-ALL has opened recently. These insights
      raise a number of new questions relevant to T-ALL pathogenesis and offer exciting
      opportunities for rational targeted therapy.

PMID- 16298818
TI  - Regulation of acquired immune system by notch signaling.
AB  - T- and B-cells are generated from hematopoietic stem cells through lymphoid
      intermediates. The interplay of intrinsic and extrinsic signals determines cell
      fate at the branch point for T- and B-cell lineages and at the post-commitment
      stage of lymphogenesis. The mature lymphocytes differentiate into effector/memory
      cells by antigen recognition, and those differentiation steps are also governed
      by a series of cell fate choices and survival signals, which allows cells to
      acquire distinct effector functions. The identification of the molecular details
      that dictate lymphocyte development and differentiation will improve
      understanding of acquired immune responses. Recent studies have revealed that
      Notch molecules, evolutionarily conserved transmembrane receptors, play key roles
      in lymphocyte development and differentiation. In this article, we review recent
      knowledge regarding the roles of Notch signaling in controlling both lymphocyte
      development and acquisition of effector functions.

PMID- 16298816
TI  - Notch signaling in hematopoietic stem cells.
AB  - The molecular basis of the hematopoietic stem cell (HSC) "niche" has gradually
      been elucidated. This new knowledge may help us understand how the self-renewal
      of HSCs is physiologically regulated and may give us clues for developing methods
      for ex vivo HSC expansion. The Notch pathway is an environmental signaling system
      that may play an important role in the HSC niche. In this review, we focus on the
      role of Notch signaling in the regulation of hematopoietic stem and progenitor
      cells in both embryo and adult hematopoiesis and clarify what is known regarding
      the self-renewal of HSCs.

PMID- 16298819
TI  - Long-term efficacy of pegylated recombinant human megakaryocyte growth and
      development factor in therapy of aplastic anemia.
AB  - Pegylated recombinant human megakaryocyte growth and development factor (PEG
      rHuMGDF) potently stimulates platelet production in humans, mitigates
      thrombocytopenia associated with nonmyeloablative chemotherapy, and reduces the
      need for platelet transfusions. Its long-term effect in patients, however, is not
      well understood. We report a patient with aplastic anaemia who received 3 cycles
      of PEG-rHuMGDF 3 times a week for up to 2 years. Platelet counts slightly
      increased 1 week after the initiation of PEG-rHuMGDF therapy, bleeding episodes
      decreased, and there was no need for platelet transfusion. Administration of PEG
      rHuMGDF increased not only platelet numbers but also reticulocyte counts, and
      reduced the need for erythrocyte transfusions as well. There were no significant
      adverse events, and no neutralizing antibodies were detected in the patient.

PMID- 16298820
TI  - Very severe iron-deficiency anemia in a patient with celiac disease and bulimia
      nervosa: a case report.
AB  - A 29-year-old woman presented to the emergency department with exhaustion,
      fatigue, and abdominal pain. She reported having received a diagnosis of bulimia
      nervosa 10 years before. On examination, she had a marked pallor and was severely
      malnourished. Laboratory analysis revealed a dramatically low hemoglobin level of
      1.7 g/dL (ref: 11.5-15.8 g/dL). Serum iron was quantified as 1.4 micromol/L (ref:
      7-26 micromol/L), ferritin as 5 ng/mL (ref: 10-120 ng/mL), and the level of serum
      transferrin as 212 mg/dL (ref: 200-360 mg/dL). A duodenal biopsy revealed villous
      atrophy in the mucosal layer indicative for celiac disease. This diagnosis was
      confirmed by serum levels of endomysial antibodies, tissue transglutaminase
      antibody, and antigliadin antibodies. The newly diagnosed gluten-sensitive
      enteropathy is likely to be in part responsible for the severe symptoms reported.
      The extent of hemoglobin decline in combination with an astonishing lack of
      critical symptoms seen in this patient is a rarity. We conclude that anorectic
      patients with severe anemia and malnutrition should be evaluated for the presence
      of additional somatic conditions.

PMID- 16298821
TI  - Acute tumor lysis syndrome induced by rituximab in diffuse large B-cell lymphoma.
AB  - Acute tumor lysis syndrome (ATLS) is a well-known complication of chemotherapy in
      patients with rapidly proliferative hematopoietic malignancies such as lymphoma
      and leukemia. Rituximab anti-CD20 monoclonal antibody, an alternative to
      chemotherapy in the treatment of low-grade follicular lymphoma, also has been
      associated with ATLS. Rituximab-induced ATLS has been reported in 2 patients with
      chronic lymphocytic leukemia and in 2 patients with non-Hodgkin's lymphoma. I
      report another case of rituximab-induced ATLS in a patient with diffuse large B
      cell lymphoma and review the cases in the literature.

PMID- 16298823
TI  - Necrotizing enterocolitis in acute lymphoblastic leukemia patients: department
      experience.
AB  - Necrotizing enterocolitis is a severe complication of high-dose chemotherapy in
      patients with hematopoietic malignancies. Some patients with severe mucositis may
      develop necrosis of the intestine, leading to typhlitis and perforation of the
      intestinal tract. The patients have few obvious symptoms; thus, early diagnosis
      and prompt treatment of intestinal necrosis or bowel perforation seem critical
      for a good overall treatment outcome. We present 5 cases of intraabdominal
      complications in patients with acute lymphoblastic leukemia. All patients who
      underwent surgery survived the postoperative period. We also present a suggested
      algorithm for treatment of acute abdomen complications in leukemic patients.

PMID- 16298822
TI  - Multilineage involvement of light microscopic myeloperoxidase-negative acute
      leukemia.
AB  - The classification of acute leukemia has traditionally been based on a
      combination of morphology and cytochemical staining data, including
      myeloperoxidase (MPO) reaction; however, a recent World Health Organization (WHO)
      classification entails use of cytogenetic and molecular findings in addition to
      the classic morphological and immunophenotypic analyses. Nevertheless, there have
      been rare cases in which blastic cells show multilineage phenotypes. These cases
      may be classified as acute leukemia of ambiguous lineage in the recent WHO
      classification. We report the case of a 49-year-old man with acute leukemia with
      multilineage phenotypes. Morphological findings led to a diagnosis of acute
      myeloid leukemia M2 by the French-American-British classification, but at light
      microscopy the results of MPO staining were negative for blast cells. In
      contrast, results of reverse transcription polymerase chain reaction and
      fluorescence-activated cell sorter analyses were positive for expression of MPO
      messenger RNA and protein. The blast cells expressed CD4, CD19, CD22, CD33, CD38,
      CD79a, and HLA-DR and showed rearrangement of the immunoglobulin heavy chain and
      TCR-3 genes. Results of immunoelectron microscopic analysis of the blast cells
      were positive for MPO, CD19, CD33, CD34, CD38 and glycophorin A but not for
      platelet peroxidase. According to these results, the blast cells had at least 4
      lineage phenotypes. We concluded that the multiparameter analyses conducted in
      this case, including immunological and ultrastructural assays, were important in
      arriving at the appropriate diagnosis of acute leukemia of ambiguous lineage in
      the new WHO classification.

PMID- 16298824
TI  - Acute respiratory distress syndrome after rituximab infusion.
AB  - Rituximab, a humanized monoclonal antibody approved for malignant lymphoma, is
      being increasingly, effectively, and safely used for immune thrombocytopenic
      purpura (ITP) and other humoral autoimmune disorders. We report the case of a 43
      year-old man with ITP refractory to steroids and intravenous immunoglobulin who
      developed acute respiratory distress syndrome (ARDS) after a single infusion of
      rituximab. Dyspnea, hypoxemia, and pleuritic chest pain occurred within 24 hours
      of rituximab administration, and there was no other apparent explanation.
      Progressive hypoxemia mandated endotracheal intubation 1 week after rituximab
      administration and led to death 4 weeks after admission. ARDS has been associated
      with the administration of other monoclonal antibodies, such as infliximab,
      gemtuzumab ozogamicin, and OKT3 and is believed to be directly mediated by
      release of proinflammatory cytokines. ARDS is rarely associated with rituximab
      infusion for lympho-proliferative disorders, but it should be considered by those
      administering rituximab, especially when a patient develops severe pulmonary
      symptoms soon after infusion.

PMID- 16298825
TI  - Fas, Fas-associated death domain-like interleukin 1beta-converting enzyme-like
      inhibitory protein, and apoptotic features of elderly acute myeloid leukemia
      based on response to induction chemotherapy.
AB  - A study was performed to examine the clinical outcome of triple-combination
      induction chemotherapy in 26 elderly Korean acute myeloid leukemia (AML) patients
      and to investigate apoptotic responses during and after treatment to determine
      whether the responses can be used as prognostic markers. Patients who had Western
      blot or polymerase chain reaction analysis findings of higher expression levels
      of Fas-associated death domain-like interleukin 1beta-converting enzyme-like
      inhibitory protein (FLIP) on day 7 after chemotherapy were more likely to have
      complete remission, but there was less or no correlation with Fas or a
      proapoptosis/apoptosis reaction. Expression of FLIP molecules may be, at least in
      part, an early prognostic indicator in the treatment of elderly AML patients.

PMID- 16298826
TI  - Use of imatinib mesylate for favorable control of hypercalcemia mediated by
      parathyroid hormone-related protein in a patient with chronic myelogenous
      leukemia at blast phase.
AB  - The case of a 72-year-old woman with chronic myelogenous leukemia in blast phase
      (BP) with hypercalcemia is reported. Bone x-ray examination revealed multiple
      osteolytic lesions throughout the body. The serum level of parathyroid hormone
      related protein (PTHrP) was elevated, and PTHrP messenger RNA (mRNA) was
      detectable in the peripheral blood mononuclear cells (PBMNC) at BP but was not
      detectable at chronic phase (CP).Treatment with conventional chemotherapy did not
      completely control either serum calcium level or serum PTHrP level. Treatment
      with imatinib mesylate (imatinib) alone rapidly normalized these parameters in
      parallel with a decrease in the number of blast cells. The treatment also
      maintained the patient in good condition for approximately 3 months, even though
      the number of blast cells, serum calcium level, serum PTHrP level, and PTHrP mRNA
      level increased at the terminal stage. Mutations of the p53, K-Ras, and BCR-ABL
      genes in PBMNC at BP were absent. A noteworthy feature in this patient was that
      PBMNC at BP but not at CP showed high Lyn mRNA expression. Taken together the
      findings showed that production of PTHrP by blast cells was favorably controlled
      by imatinib therapy alone. Imatinib may prolong survival time at BP even though
      the patients have the complication of PTHrP-mediated hypercalcemia.

PMID- 16298827
TI  - Primary tracheal lymphoma: case report and literature review.
AB  - We describe a 20-year-old Japanese woman with anaplastic large cell lymphoma in
      whom primary tracheal involvement was associated with life-threatening airway
      obstruction. After debulking surgery, the patient was successfully treated with
      chemotherapy and radiotherapy. A total of 28 cases of primary tracheal lymphoma
      were reviewed. Common clinical features included predominance of localized
      disease, respiratory symptoms resembling acute asthma, absence of hemoptysis, and
      rapid progression of tracheal stenosis. Various histological subtypes of primary
      tracheal lymphoma exist and are likely to determine prognosis.

PMID- 16298828
TI  - Severe hepatic injury caused by imatinib mesylate administered for the treatment
      of chronic myeloid leukemia and the efficacy of prednisolone for its management.
AB  - Imatinib mesylate is a specific inhibitor of BCR-ABL tyrosine kinase, which is
      now widely used for the treatment of chronic myeloid leukemia (CML) with a high
      efficacy. Although severe hepatic injury caused by imatinib mesylate is rare,
      such a side effect may force patients to discontinue taking imatinib mesylate. In
      the present paper, we report on the case of a 51-year-old woman with CML who
      experienced hepatic injury with severe hyperbilirubinemia caused by imatinib
      mesylate. The findings from a liver biopsy specimen and her clinical course
      suggested the hepatic injury to presumably have been caused by an allergic
      mechanism. The co-administration of prednisolone was thus tried, and she has been
      able to continue imatinib mesylate administration without any liver dysfunction
      and finally was able to obtain a complete cytogenetic response.We therefore
      recommend that prednisolone should be tried when severe hepatic injury caused by
      imatinib mesylate is observed, since it might enable such patients to continue
      imatinib mesylate treatment and thereby improve the prognosis in such cases.

PMID- 16298829
TI  - Multiple constitutional chromosome translocations of familial nature in
      Philadelphia chromosome-positive chronic myeloid leukemia: a report on a unique
      case.
AB  - A case of Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia (CML)
      featuring 2 additional balanced translocations, t(2;5) and t(6;12), as well as a
      robertsonian translocation, t(13;14), was diagnosed by routine bone marrow
      karyotyping. The breakpoints did not involve previously described CML-related
      chromosomal regions in any of the 3 translocations. Despite the patient's partial
      response following imatinib therapy, all Ph(-) bone marrow metaphases
      persistently had the 3 additional chromosomal changes. Moreover, stimulated
      peripheral B-lymphocytes from the patient also showed the same chromosomal
      changes, suggesting that we had found a complex constitutional chromosome
      aberration unrelated to the leukemia. Peripheral blood karyotype analyses of 6 of
      the 7 closest relatives from 3 generations demonstrated at least 1 of these
      aberrations, although in different combinations. Standard bone marrow or
      peripheral blood karyotyping of hematologic disorders may uncover otherwise
      symptomless, unrelated constitutional changes together with disease-specific
      chromosome aberrations.A triple constitutional chromosome aberration combined
      with a hematologic disorder has not been described until now. In addition,
      multiple constitutional aberrations persisting through at least 3 generations
      seem to be extremely rare. At present, no direct evidence exists to support a
      causative relationship between the familial translocations and leukemogenesis.

PMID- 16298830
TI  - Highly conserved antigenic structure of the factor VIII C2 domain in some
      mammals.
AB  - To elucidate differences in the antigenic structure of factor VIII (FVIII) among
      mammals, we evaluated cross-reactivities of well-defined antihuman FVIII
      antibodies with canine and other mammalian FVIII proteins. Monoclonal antibodies
      against human FVIII recognizing the A1 domain in the heavy chain and the A3
      domain in the light chain showed 2.7% and 0% cross-reactivities, respectively,
      with canine FVIII. The cross-reactivities of 2 alloantibodies and a monoclonal
      antibody that recognized the A2 domain in the heavy chain were 10%, 38%, and 0%,
      respectively. On the other hand, 2 kinds of alloantibodies and a monoclonal
      antibody recognizing the C2 domain in the light chain showed 160%, 390%, and 130%
      cross-reactivity, respectively, with canine FVIII. The anti-C2 monoclonal
      antibody (NMC-VIII/5) showed a type 2 inactivating property when tested with
      canine and human plasma. Moreover, cross-reactivities of NMC-VIII/5 with simian
      and feline FVIII were 54.5% and 82.8%, respectively, while the cross-reactivities
      of the anti-A2 monoclonal antibody (JR8) with simian and feline FVIII were 1.3%
      and 0%, respectively. These findings suggest that the antigenic structure of the
      C2 epitope has remained relatively conserved throughout mammalian evolution in
      contrast to the A2 epitope and that a canine model of hemophilia A is useful for
      FVIII inhibitor experiments.

PMID- 16298833
TI  - The general practitioner pharmacotherapy prescribing workforce: examining
      sustainability from a systems perspective.
AB  - As prescribers of opioid pharmacotherapies, general practitioners (GPs) are
      pivotal to the sustainability of opioid pharmacotherapy treatment services. The
      goal of this study was to examine the nature and sustainability of the Australian
      GP prescriber workforce in order to inform future programmes and policy
      development in this area. Data were collected from four Australian states: South
      Australia, Queensland, Victoria and New South Wales. Key features of the
      available data were: a heavy client load carried by a small number of
      prescribers, a high proportion of trained but inactive prescribers, and a high
      proportion (one-third to two-thirds) of medical practitioners who undertake
      training but do not take up prescribing, i.e. a high attrition rate. Available
      data indicate significant shortfalls in the number of prescribers available in
      each state to service this patient population. Across all states a relatively
      small number of prescribers were providing services for the majority of methadone
      clients. In order to achieve sustainable, high quality prescriber service
      provision, workforce development strategies are needed which focus on recruitment
      of new prescribers, and the support and retention of existing and inactive
      prescribers. Establishment of systematic and detailed data collection systems
      should also be considered a priority.

PMID- 16298831
TI  - Case of a patient with progressive adult T-cell leukemia/lymphoma treated
      successfully by reduced-intensity conditioning stem cell transplantation from an
      HLA-incompatible related donor.
AB  - A 61-year-old man with progressive adult T-cell leukemia/lymphoma (ATLL)
      successfully received reduced-intensity conditioning stem cell transplantation
      (RIST) without T-cell depletion (TCD) from his HLA-incompatible son, who had
      negative results for human T-lymphotropic virus type 1 (HTLV-1) (1-locus, 1
      allele mismatch in the graft-versus-host [GVH] direction; 2-loci, 1-allele
      mismatch in the host-versus-graft direction). The preparatory regimen consisted
      of fludarabine, busulfan, and rabbit antithymocyte globulin. GVH disease (GVHD)
      prophylaxis consisted of short-term administration of methotrexate, tacrolimus,
      and methylprednisolone. The patient achieved complete donor chimerism on day 30
      after transplantation. On approximately day 50 the patient started to experience
      steroid-refractory skin GVHD (grade IV), which was successfully managed with
      basiliximab (anti-CD25 monoclonal antibody) and mycophenolate mofetil (MMF).
      Serial analysis of HTLV-1 proviral load by quantitative polymerase chain reaction
      analysis using whole peripheral blood demonstrated undetectable levels from day
      90. At the time of this writing the patient had been in complete remission for
      more than 16 months. The results in this case suggest the potential of non-TCD
      RIST from an HLA-incompatible relative donor as an alternative source of
      hematopoietic stem cells even for an elderly patient with advanced ATLL. In
      addition, basiliximab combined with MMF may be effective for the treatment of
      steroid-refractory skin GVHD without deteriorating the graft-versus-ATL effect.

PMID- 16298832
TI  - Severe hypercholesterolemia associated with decreased hepatic triglyceride lipase
      activity and pseudohyponatremia in patients after allogeneic stem cell
      transplantation.
AB  - A 55-year-old woman with Ph-negative acute lymphoblastic leukemia in primary
      induction failure received allogeneic peripheral blood stem cell transplantation
      from her HLA-compatible sister. Pseudohyponatremia developed due to extreme
      hypercholesterolemia of 4091 mg/dL accompanied by lipoprotein X and lipoprotein
      Y. The hypercholesterolemia was caused by cholestasis due to chronic GVHD and
      ischemic cholangiopathy. In addition, we found that hepatic triglyceride lipase
      (HTGL) activity was severely decreased, which could be another novel factor
      causing extreme hypercholesterolemia after allogeneic transplantation. The total
      cholesterol has been gradually decreasing followed by the improvement of
      cholestasis with bezafibrate, ursodeoxycholic acid and prednisone treatments, and
      by a slight increase in HTGL-protein. To our knowledge, this is the first report
      to describe the association of decreased HTGL with extreme hypercholesterolemia
      after allogeneic transplantation.

PMID- 16298834
TI  - The definition of opioid-related deaths in Australia: implications for
      surveillance and policy.
AB  - The reported number of deaths caused by opioid use depends on the definition of
      an opioid-related death. In this study, we used Australian Bureau of Statistics
      (ABS) mortality data to illustrate how choice of classification codes used to
      record cause of death can impact on the statistics reported for national
      surveillance of opioid deaths. Using International Classification of Diseases
      version 10 (ICD-10) codes from ABS mortality data 1997-2002, we examined all
      deaths where opioids were reported as a contributing or underlying cause. For the
      6-year period there was a total of 5,839 deaths where opioids were reported.
      Three possible surveillance definitions of accidental opioid-related deaths were
      examined, and compared to the total number of deaths where opioids were reported
      for each year. Age restrictions, often placed on surveillance definitions, were
      also examined. As expected, the number of deaths was higher with the more
      inclusive definitions. Trends in deaths were found to be similar regardless of
      the definition used; however, a comparison between Australian states revealed up
      to a twofold difference in the absolute numbers of accidental opioid-related
      deaths, depending on the definition. Any interpretation of reported numbers of
      opioid deaths should specify any restrictions placed on the data, and describe
      the implications of definitions used.

PMID- 16298835
TI  - The characteristics of heroin users entering treatment: findings from the
      Australian treatment outcome study (ATOS).
AB  - The current study aimed to describe the characteristics (demographics, drug use,
      mental and physical health) of entrants to treatment for heroin dependence in
      three treatment modalities; and to compare these characteristics with heroin
      users not in or seeking treatment. Participants were 825 current heroin users
      recruited from Sydney, Adelaide and Melbourne: 277 entering
      methadone/buprenorphine maintenance treatment (MT), 288 entering detoxification
      (DTX), 180 entering drug-free residential rehabilitation (RR) and 80 not in
      treatment (NT). Treatment entrants were generally long-term heroin users with
      previous treatment experience. The majority of the sample (55%) were criminally
      active in the month preceding interview. Injection-related health problems (74%)
      and a history of heroin overdose (58%) were commonly reported. There were high
      degrees of psychiatric co-morbidity, with 49% reporting severe psychological
      distress, 28% having current major depression, 37% having attempted suicide and
      42% having a lifetime history of post-traumatic stress disorder. Personality
      disorders were also prevalent, with 72% meeting criteria for antisocial
      personality disorder and 47% screening positive for borderline personality
      disorder. Striking similarities were noted between the non-treatment and
      treatment groups in length of heroin use career, drug use and treatment
      histories.

PMID- 16298836
TI  - Heroin treatment demand in South Africa: trends from two large metropolitan sites
      (January 1997-December 2003).
AB  - Accurate prevalence data on heroin use, that points to where problems exist and
      the extent of these problems, is necessary to guide the formulation of effective
      substance abuse policy and practice. The purpose of this study was to provide
      surveillance information about the nature and extent of heroin use in South
      Africa. Data were collected from 41 specialist alcohol and other drug treatment
      centres in two metropolitan sites (Cape Town and Gauteng Province) between
      January 1997 and December 2003. Treatment indicators point to a substantial
      increase in heroin use over time. Most heroin users in treatment tend to be
      white, male, between the ages of 21 and 24 years and tend to smoke rather than
      inject the substance. However, this profile is changing. These emerging trends
      point to the possibility of heroin use becoming a serious health and social issue
      in South Africa and demonstrate the need for continued monitoring of heroin use
      patterns in the future and the development of a strategic plan for intervening
      before the situation deteriorates further.

PMID- 16298837
TI  - Non-fatal heroin overdose, treatment exposure and client characteristics:
      findings from the Australian treatment outcome study (ATOS).
AB  - The relationship between treatment exposure, drug use, psychosocial variables and
      non-fatal heroin overdose was examined among a cohort of 495 heroin users, re
      interviewed at 12 months. The 12-month overdose rate declined from 24% to 12%,
      and the proportion administered naloxone declined from 15% to 7%. There were
      significant reductions in overdose among those who entered maintenance therapies
      (22% to 4%) and residential rehabilitation (33% vs. 19%) at baseline, but not
      among those who entered detoxification or were not entering treatment. The total
      number of treatment days received over the follow-up period was associated
      independently with a reduced risk of overdose. Each extra treatment day was
      associated with a 1% reduction in risk of overdose over the follow-up period. By
      contrast, more treatment episodes were associated with an increased risk of
      overdose (OR 1.62). Other independent predictors of overdose over follow-up were
      more extensive polydrug use (OR 1.40), and having overdosed in the year preceding
      the study (OR 7.87).

PMID- 16298838
TI  - Characteristics of treatment provided for amphetamine use in New South Wales,
      Australia.
AB  - The purpose of this study was to examine the types of treatment services provided
      for amphetamine use, the characteristics of amphetamine treatment clients and the
      geographic areas most affected by amphetamine treatment provision within New
      South Wales (NSW), Australia. Data on completed amphetamine treatment episodes
      were extracted from the NSW Minimum Data Set for Alcohol and Other Drug Treatment
      Services for the year 2002/03 (n = 4,337). The geographic area of treatment
      presentations was based on the location of the treatment service, and was
      categorized as metropolitan, regional or rural. Treatment disproportionately
      affected regional and rural NSW, and treatment clients often presented with
      concurrent cannabis and/or alcohol problems. Clients were overwhelmingly
      injecting drug users with poor socio-demographic characteristics. Counselling was
      the most common treatment service provided, followed by detoxification and
      residential rehabilitation. Detoxification was usually provided in an in-patient
      setting, particularly within metropolitan NSW. Compliance with residential
      rehabilitation was notably poor. In conclusion, the development of appropriate
      interventions for amphetamine use needs to consider that the majority of
      treatment recipients will be based in a regional or rural setting, and treating
      amphetamine users will often involve treatment of concurrent cannabis and alcohol
      problems. The nature and appropriateness of treatment services provided for
      amphetamine use needs to be reviewed in detail, and further research is needed
      into the nature of problematic amphetamine use and factors affecting treatment
      demand in regional and rural NSW.

PMID- 16298839
TI  - Application of the Transtheoretical Model to substance abuse: historical
      development and future directions.
AB  - As a growing literature has documented applications of the Transtheoretical Model
      (TTM) to substance abuse, the utility or futility of such an application has been
      debated widely. The purpose of this paper is to critically examine the TTM, and
      its conceptual and empirical applications to the field of substance abuse. This
      review focuses not only on the stage of change dimension of the TTM, but also the
      processes, decisional balance, and self-efficacy dimensions, which have received
      less attention in earlier reviews. Particular emphasis is placed on the
      measurement and conceptualization of the stage of change construct. Unanswered
      questions and directions for future research are identified. It is concluded
      that, to effectively determine the TTM's applicability to substance abuse, all
      dimensions must be more fully developed, validated and evaluated across a range
      of substance abuse problems. Further, prospective studies are needed to determine
      the predictive utility of the TTM, and evaluation of TTM-matched interventions
      will help to address the model's specificity.

PMID- 16298840
TI  - Ethical challenges and responses in harm reduction research: promoting applied
      communitarian ethics.

PMID- 16298841
TI  - Illicit substance supply and abuse in 2000-2004: an approach to assess the
      outcome of the war on drug operation.

PMID- 16298844
TI  - Radiofrequency ablation of hepatic tumors: simulation, planning, and contribution
      of virtual reality and haptics.
AB  - For radiofrequency ablation (RFA) of liver tumors, evaluation of vascular
      architecture, post-RFA necrosis prediction, and the choice of a suitable needle
      placement strategy using conventional radiological techniques remain difficult.
      In an attempt to enhance the safety of RFA, a 3D simulator, treatment planning,
      and training tool, that simulates the insertion of the needle, the necrosis of
      the treated area, and proposes an optimal needle placement, has been developed.
      The 3D scenes are automatically reconstructed from enhanced spiral CT scans. The
      simulator takes into account the cooling effect of local vessels greater than 3
      mm in diameter, making necrosis shapes more realistic. Optimal needle positioning
      can be automatically generated by the software to produce complete destruction of
      the tumor, with maximum respect of the healthy liver and of all major structures
      to avoid. We also studied how the use of virtual reality and haptic devices are
      valuable to make simulation and training realistic and effective.

PMID- 16298845
TI  - Three-dimensional analysis for radio-frequency ablation of liver tumor with blood
      perfusion effect.
AB  - Increase of temperature above 50 approximately 60 degrees C for few minutes by
      the emitted radio-frequency (RF) energy has been shown to be able to denaturate
      the intracellular proteins and destruct membranes of tumor cells. To improve the
      efficacy of this thermal therapy, it is important to investigate factors that may
      affect the RF heating characteristics for the hepatocellular carcinoma and
      metastatic liver tumors. In order to make sure the applied RF energy is adequate
      to ablate the target tumor, a 3D thermoelectric analysis for the system
      consisting of liver, liver arteries and 4 mm diameter tumor is conducted. The
      effect of blood perfusion is addressed in this study.

PMID- 16298846
TI  - Numerical prediction of freezing fronts in cryosurgery: comparison with
      experimental results.
AB  - Recent developments in scientific computing now allow to consider realistic
      applications of numerical modelling to medicine. In this work, a numerical method
      is presented for the simulation of phase change occurring in cryosurgery
      applications. The ultimate goal of these simulations is to accurately predict the
      freezing front position and the thermal history inside the ice ball which is
      essential to determine if cancerous cells have been completely destroyed. A semi
      phase field formulation including blood flow considerations is employed for the
      simulations. Numerical results are enhanced by the introduction of an anisotropic
      remeshing strategy. The numerical procedure is validated by comparing the
      predictions of the model with experimental results.

PMID- 16298847
TI  - Coloscopy simulation: towards endoscopes improvement.
AB  - Minimally invasive surgery progresses have allowed to greatly decrease patient
      suffering. A way to improve these techniques is to use active tools, which could
      adapt to the inspected environment. The development of these tools is very
      complex. So simulation methods can be significantly helpful in order to produce
      the most suitable tools while limiting the quantity of physical prototypes. We
      work on the design of a simulator for virtual coloscopy. Besides the virtual
      prototyping aspect for new active endoscopic devices, we can also use it as a
      training simulator once the device is designed. To do so, we have to address the
      simulation process of the colon. This article is mainly devoted to the
      description of the chosen models for the colon behaviour, which are used for the
      simulator. Some experimental results are presented which confirm the validity of
      the different choices. To finish, sigmoid untwisting operation is presented as a
      benchmark test to prove the efficiency of the simulator.

PMID- 16298848
TI  - Orbital and maxillofacial computer aided surgery: patient-specific finite element
      models to predict surgical outcomes.
AB  - This paper addresses an important issue raised for the clinical relevance of
      Computer-Assisted Surgical applications, namely the methodology used to
      automatically build patient-specific finite element (FE) models of anatomical
      structures. From this perspective, a method is proposed, based on a technique
      called the mesh-matching method, followed by a process that corrects mesh
      irregularities. The mesh-matching algorithm generates patient-specific volume
      meshes from an existing generic model. The mesh regularization process is based
      on the Jacobian matrix transform related to the FE reference element and the
      current element. This method for generating patient-specific FE models is first
      applied to computer-assisted maxillofacial surgery, and more precisely, to the FE
      elastic modelling of patient facial soft tissues. For each patient, the planned
      bone osteotomies (mandible, maxilla, chin) are used as boundary conditions to
      deform the FE face model, in order to predict the aesthetic outcome of the
      surgery. Seven FE patient-specific models were successfully generated by our
      method. For one patient, the prediction of the FE model is qualitatively compared
      with the patient's post-operative appearance, measured from a computer tomography
      scan. Then, our methodology is applied to computer-assisted orbital surgery. It
      is, therefore, evaluated for the generation of 11 patient-specific FE poroelastic
      models of the orbital soft tissues. These models are used to predict the
      consequences of the surgical decompression of the orbit. More precisely, an
      average law is extrapolated from the simulations carried out for each patient
      model. This law links the size of the osteotomy (i.e. the surgical gesture) and
      the backward displacement of the eyeball (the consequence of the surgical
      gesture).

PMID- 16298849
TI  - Airflow modeling of steady inspiration in two realistic proximal airway trees
      reconstructed from human thoracic tomodensitometric images.
AB  - Detailed description of the flow field in human airways is highly important to
      better understand human breathing and provide a patient's customized diagnosis.
      An integrated numerical simulation platform is presently proposed in order to
      incorporate medical images into a numerical software to calculate flow field and
      to analyze it in terms of fluid dynamics. The platform was set up to compute
      steady inspiratory airflow in realistic human airways reconstructed from
      tomodensitometric medical images at resting breathing conditions. This morpho
      functional simulation platform has been tested retrospectively with two CT
      scanned patient airway morphological models: (i) a normal airway model (subject
      A) with no evidence of morphological alteration and (ii) a highly altered airway
      model (subject B) exhibiting a severe stenosis in the right main bronchus. First,
      various morphological aspects proper to each airway model are provided to show
      the performance and interest of the reconstruction method. Second, we describe
      the three-dimensional flow patterns associated to the global morphological
      features, which are mainly shared by the present realistic models and previous
      idealistic airway models. Finally, the flow characteristics associated to local
      morphological features specific to realistic airway models are discussed. The
      results demonstrate that the morpho-functional simulation platform is able to
      capture the main features of airway velocity patterns but also more specific
      airflow patterns which are related to customized patient morphological features
      such as laminar vortex formation. The present results suggest that the proposed
      airway functional imaging platform is adequate to provide most of functional
      information related to airflow and enable a patient to patient diagnosis.

PMID- 16298850
TI  - An image-based computational model of oscillatory flow in the proximal part of
      tracheobronchial trees.
AB  - A computational model of an oscillatory laminar flow of an incompressible
      Newtonian fluid has been carried out in the proximal part of human
      tracheobronchial trees, either normal or with a strongly stenosed right main
      bronchus. After acquisition with a multislice spiral CT, the thoracic images are
      processed to reconstruct the geometry of the trachea and the first six bronchus
      generations and to virtually travel inside this duct network. The facetisation
      associated with the 3D reconstruction of the tracheobronchial tree is improved to
      get a computation-adapted surface triangulation, which leads to a volumic mesh
      composed of tetrahedra. The Navier-Stokes equations associated with the classical
      boundary conditions and different values of the flow dimensionless parameters are
      solved using the finite element method. The airways are supposed to be rigid
      during rest breathing. The flow distribution among the set of bronchi is
      determined during the respiratory cycle. Cycle reproducibility and mesh size
      effects on the numerical results are examined. Helpful qualitative data are
      provided rather than accurate quantitative results in the context of
      multimodelling, from image processing to numerical simulations.

PMID- 16298851
TI  - Anisotropic adaptive finite element method for modelling blood flow.
AB  - In this study, we present an adaptive anisotropic finite element method (FEM) and
      demonstrate how computational efficiency can be increased when applying the
      method to the simulation of blood flow in the cardiovascular system. We use the
      SUPG formulation for the transient 3D incompressible Navier-Stokes equations
      which are discretised by linear finite elements for both the pressure and the
      velocity field. Given the pulsatile nature of the flow in blood vessels we have
      pursued adaptivity based on the average flow over a cardiac cycle. Error
      indicators are derived to define an anisotropic mesh metric field. Mesh
      modification algorithms are used to anisotropically adapt the mesh according to
      the desired size field. We demonstrate the efficiency of the method by first
      applying it to pulsatile flow in a straight cylindrical vessel and then to a
      porcine aorta with a stenosis bypassed by a graft. We demonstrate that the use of
      an anisotropic adaptive FEM can result in an order of magnitude reduction in
      computing time with no loss of accuracy compared to analyses obtained with
      uniform meshes.

PMID- 16298852
TI  - How plate positioning impacts the biomechanics of the open wedge tibial
      osteotomy; a finite element analysis.
AB  - A numerical model of the medial open wedge tibial osteotomy based on the finite
      element method was developed. Two plate positions were tested numerically. In a
      configuration, (a), the plate was fixed in a medial position and (b) in an
      anteromedial position. The simulation took into account soft tissues preload,
      muscular tonus and maximal gait load.The maximal stresses observed in the four
      structural elements (bone, plate, wedge, screws) of an osteotomy with plate in
      medial position were substantially higher (1.13-2.8 times more) than those
      observed in osteotomy with an anteromedial plate configuration. An important
      increase (1.71 times more) of the relative micromotions between the wedge and the
      bone was also observed. In order to avoid formation of fibrous tissue at the bone
      wedge interface, the osteotomy should be loaded under 18.8% (approximately 50 kg)
      of the normal gait load until the osteotomy interfaces union is achieved.

PMID- 16298853
TI  - A stochastic model of elbow flexion strength for subjects with and without long
      head biceps tear.
AB  - The classical approach of musculoskeletal modeling is to predict muscle forces
      and joint torques with a deterministic model constructed from parameters of an
      average subject. However, this type of model does not perform well for outliers,
      and does not model the effects of parameter variability. In this study, a Monte
      Carlo model was used to stochastically simulate the effects of variability in
      musculoskeletal parameters on elbow flexion strength in healthy normals, and in
      subjects with long head biceps (LHB) rupture. The goal was to determine if
      variability in elbow flexion strength could be quantifiably explained with
      variability in musculoskeletal parameters. Parameter distributions were
      constructed from data in the literature. Parameters were sampled from these
      distributions and used to predict muscle forces and joint torques. The median and
      distribution of measured joint torque was predicted with small errors (< 5%).
      Muscle forces for both cases were predicted and compared. In order to predict
      measured torques for the case of LHB rupture, the median force and mean cross
      sectional area in the remaining elbow flexor muscles is greater than in healthy
      normals. The probabilities that muscle forces for the Tear case exceed median
      muscle forces for the No-Tear case are 0.98, 0.99 and 0.79 for SH Biceps,
      brachialis and brachioradialis, respectively. Differences in variability of
      measured torques for the two cases are explained by differences in parameter
      variability.

PMID- 16298854
TI  - Search for critical loading condition of the spine--a meta analysis of a
      nonlinear viscoelastic finite element model.
AB  - The relative vulnerability of spinal motion segments to different loading
      combinations remains unknown. The meta-analysis described here using the results
      of a validated L2-L3 nonlinear viscoelastic finite element model was designed to
      investigate the critical loading and its effect on the internal mechanics of the
      human lumbar spine. A Box-Behnken experimental design was used to design the
      magnitude of seven independent variables associated with loads, rotations and
      velocity of motion. Subsequently, an optimization method was used to find the
      primary and secondary variables that influence spine mechanical output related to
      facet forces, disc pressure, ligament forces, annulus matrix compressive/shear
      stresses and anulus fibers strain. The mechanical responses with respect to the
      two most-relevant variables were then regressed linearly using the response
      surface quadratic model. Axial force and sagittal rotation were identified as the
      most-relevant variables for mechanical responses. The procedure developed can be
      used to find the critical loading for finite element models with multi input
      variables. The derived meta-models can be used to predict the risk associated
      with various loading parameters and in setting safer load limits.

PMID- 16298855
TI  - Finite element simulation of spinal deformities correction by in situ contouring
      technique.
AB  - Biomechanical models have been proposed in order to simulate the surgical
      correction of spinal deformities. With these models, different surgical
      correction techniques have been examined: distraction and rod rotation. The
      purpose of this study was to simulate another surgical correction technique: the
      in situ contouring technique. In this way, a comprehensive three-dimensional
      Finite Element (FE) model with patient-specific geometry and patient-specific
      mechanical properties was used. The simulation of the surgery took into account
      elasto-plastic behavior of the rod and multiple moments loading and unloading
      representing the surgical maneuvers. The simulations of two clinical cases of
      hyperkyphosis and scoliosis were coherent with the surgeon's experience.
      Moreover, the results of simulation were compared to post-operative 3D
      measurements. The mean differences were under 5 degrees for vertebral rotations
      and 5 mm for spinal lines. These simulations open the way for future predictive
      tools for surgical planning.

PMID- 16298856
TI  - A shell finite element model of the pelvic floor muscles.
AB  - The pelvic floor gives support to the organs in the abdominal cavity. Using the
      dataset made public in (Janda et al. J. Biomech. (2003) 36(6), pp. 749-757), we
      have reconstructed the geometry of one of the most important parts of the pelvic
      floor, the levator ani, using NURB surfaces. Once the surface is triangulated,
      the corresponding mesh is used in a finite element analysis with shell elements.
      Based on the 3D behavior of the muscle we have constructed a shell that takes
      into account the direction of the muscle fibers and the incompressibility of the
      tissue. The constitutive model for the isotropic strain energy and the passive
      strain energy stored in the fibers is adapted from Humphrey's model for cardiac
      muscles. To this the active behavior of the skeletal muscle is added. We present
      preliminary results of a simulation of the levator ani muscle under pressure and
      with active contraction. This research aims at helping simulate the damages to
      the pelvic floor that can occur after childbirth.

PMID- 16298857
TI  - Attenuation of oxidative stress in HL-1 cardiomyocytes improves mitochondrial
      function and stabilizes Hif-1alpha.
AB  - HL-1 cardiomyocytes were subjected to simulated hypoxia, in the presence of
      cobalt chloride, which resulted in reduction of cell viability and induction of
      DNA laddering, indicating the activation of the apoptotic cascade. In the
      presence of trolox, ascorbic acid, melatonin and the hybrid compound of trolox
      and lipoic acid (LaT 3a), cell viability was increased, with LaT 3a exhibiting
      the best effect. Antioxidant treatment restored ATP levels, abolished laddering
      of DNA, abrogated MPTP opening, Bax translocation to the mitochondria and
      cytochrome c release to the cytoplasm. Moreover, severe hypoxia, was found to
      destabilize hypoxia inducible factor-1alpha (Hif-1alpha) mRNA. Reduction of
      oxidative stress attenuated this effect, implying a possible anti-apoptotic
      action of the master regulator of hypoxia response. Our data suggest that
      antioxidants can maintain cell function and survival by inhibiting the
      mitochondrial apoptotic pathway and stabilizing Hif-1alpha.

PMID- 16298858
TI  - Oxidative stress promotes the increase of matrix metalloproteinases-2 and -9
      activities in the feto-placental unit of diabetic rats.
AB  - Maternal diabetes increases the risk of congenital malformations, placental
      dysfunction and diseases in both the neonate and the offspring's later life.
      Oxidative stress has been involved in the etiology of these abnormalities. Matrix
      metalloproteases (MMPs), involved in multiple developmental pathways, are
      increased in the fetus and placenta from diabetic experimental models. As
      oxidants could be involved in the activation of latent MMPs, we investigated a
      putative relationship between MMPs activities and oxidative stress in the feto
      placental unit of diabetic rats at midgestation. We found that H2O2 enhanced and
      that superoxide dismutase (SOD) reduced MMPs activities in the maternal side of
      the placenta and in the fetuses from control and diabetic rats. MMPs were not
      modified by oxidative status in the fetal side of the placenta. Lipid
      peroxidation was enhanced in the maternal and fetal sides of the placenta and in
      the fetus from diabetic rats when compared to controls, and gradually decreased
      from the maternal placental side to the fetus in diabetic animals. The activities
      of the antioxidant enzymes SOD and catalase were decreased in the maternal
      placental side, catalase activity was enhanced in the fetal placental side and
      both enzymes were increased in the fetuses from diabetic rats when compared to
      controls. Our data demonstrate changes in the oxidative balance and capability of
      oxidants to upregulate MMPs activity in the feto-placental unit from diabetic
      rats, a basis to elucidate links between oxidative stress and alterations in the
      developmental pathways in which MMPs are involved.

PMID- 16298859
TI  - Rac1-NADPH oxidase-regulated generation of reactive oxygen species mediates
      glutamate-induced apoptosis in SH-SY5Y human neuroblastoma cells.
AB  - Reactive oxygen species (ROS) are known to play an important role in glutamate
      induced neuronal cell death. In the present study, we examined whether NADPH
      oxidase serves as a source of ROS production and plays a role in glutamate
      induced cell death in SH-SY5Y human neuroblastoma cells. Stimulation of the cells
      with glutamate (100 mM) induced apoptotic cell death and increase in the level of
      ROS, and these effects of glutamate were significantly suppressed by the
      inhibitors of the NADPH oxidase, diphenylene iodonium, apocynin, and neopterine.
      In addition, RT-PCR revealed that SH-SY5Y cells expressed mRNA of gp91phox,
      p22phox and cytosolic p47phox, p67phox and p40phox, the components of the plasma
      membrane NADPH oxidase. Treatment with glutamate also resulted in activation and
      translocation of Rac1 to the plasma membrane. Moreover, the expression of
      Rac1N17, a dominant negative mutant of Rac1, significantly blocked the glutamate
      induced ROS generation and cell death. Collectively, these results suggest that
      the plasma membrane-bound NADPH oxidase complex may play an essential role in the
      glutamate-induced apoptotic cell death through increased production of ROS.

PMID- 16298860
TI  - Hispidulin: antioxidant properties and effect on mitochondrial energy metabolism.
AB  - Hispidulin (6-methoxy-5,7,4'-trihydroxyflavone) and eupafolin (6-methoxy
      5,7,3',4'-tetrahydroxyflavone), are flavonoids found in the leaves of Eupatorium
      litoralle. They have recognized antioxidant and antineoplastic properties,
      although their action mechanisms have not been previously described. We now
      report the effects of hispidulin on the oxidative metabolism of isolated rat
      liver mitochondria (Mit) and have also investigated the prooxidant and
      antioxidant capacity of both flavonoids. Hispidulin (0.05-0.2 mM) decreased the
      respiratory rate in state III and stimulated it in state IV, when glutamate or
      succinate was used as oxidizable substrate. Hispidulin inhibited enzymatic
      activities between complexes I and III of the respiratory chain. In broken Mit
      hispidulin (0.2 mM) slightly inhibited ATPase activity (25%). However, when
      intact Mit were used, the flavonoid stimulated this activity by 100%. Substrate
      energized mitochondrial swelling was markedly inhibited by hispidulin. Both
      hispidulin and eupafolin were able to promote iron release from ferritin, this
      effect being more accentuated with eupafolin with the suggestion of a possible
      involvement of H2O2 in the process. Hispidulin was incapable of donating
      electrons to the stable free radical DPPH, while eupafolin reacted with it in a
      similar way to ascorbic acid. The results indicate that hispidulin as an
      uncoupler of oxidative phosphorylation, is able to release iron from ferritin,
      but has distinct prooxidant and antioxidant properties when compared to
      eupafolin.

PMID- 16298861
TI  - Relation between oxidative stress markers and antioxidant endogenous defences
      during exhaustive exercise.
AB  - Hydrogen peroxide (H2O2) could induce oxidative damage at long distance from its
      generation site and it is also an important signalling molecule that induces some
      genes related to oxidative stress. Our objective was to study the plasma and
      blood cells capability to detoxify H2O2 after intense exercise and its
      correlation with oxidative damage. Blood samples were taken from nine
      professional cycling, participating in a mountain stage, under basal conditions
      and 3 h after the competition. Catalase and glutathione peroxidase activities
      decreased (40 and 50% respectively) in neutrophils after the cycling stage, while
      glutathione peroxidase increased (87%) in lymphocytes. Catalase protein levels
      and catalase specific activity maintained basal values after the stage in plasma.
      Catalase protein levels decreased (48%) in neutrophils and its specific activity
      increased up to plasma values after exercise. Myeloperoxidase (MPO) increased
      (39%) in neutrophils after the cycling stage. Exercise-induced hemolysis and
      lymphopenia inversely correlated with cellular markers of oxidative stress.
      Plasma malondialdehyde (MDA) directly correlated with neutrophil MPO activity and
      erythrocytes MDA. Intense exercise induces oxidative damage in blood cells as
      erythrocytes and lymphocytes, but not in neutrophils.

PMID- 16298862
TI  - The effect of alpha-phenyl-N-t-butylnitrone on ionizing radiation-induced
      apoptosis in U937 cells.
AB  - Ionizing radiation induces the production of reactive oxygen species (ROS), which
      play an important causative role in apoptotic cell death. alpha-Phenyl-N-t
      butylnitrone (PBN) is one of the most widely used spin-trapping compounds for
      investigating the existence of free radicals in biological systems. We
      investigated the effects of PBN on ionizing radiation-induced apoptosis in U937
      cells. Upon exposure to 2 Gy of gamma-irradiation, there was a distinct
      difference between the control cells and the cells pre-treated with 2 mM PBN for
      2 h in regard to apoptotic parameters, cellular redox status, mitochondria
      function and oxidative damage to cells. PBN effectively suppressed morphological
      evidence of apoptosis and DNA fragmentation in U937 cells exposed to ionizing
      radiation. The [GSSG]/[GSH+GSSG] ratio and the generation of intracellular ROS
      were higher and the [NADPH]/[NADP+ +NADPH] ratio was lower in control cells
      compared to PBN-treated cells. The ionizing radiation-induced mitochondrial
      damage reflected by the altered mitochondrial permeability transition, the
      increase in the accumulation of ROS, and the reduction of ATP production were
      significantly higher in control cells compared to PBN-treated cells. PBN pre
      treated cells showed significant inhibition of apoptotic features such as
      activation of caspase-3, up-regulation of Bax and p53, and down-regulation of Bcl
      2 compared to control cells upon exposure to ionizing radiation. This study
      indicates that PBN may play an important role in regulating the apoptosis induced
      by ionizing radiation presumably through scavenging of ROS.

PMID- 16298863
TI  - Proteomic characterization of oxidative dysfunction in human umbilical vein
      endothelial cells (HUVEC) induced by exposure to oxidized LDL.
AB  - The oxidative modification of low-density lipoprotein (LDL) and subsequent
      alteration of endothelial cell function are generally accepted as an important
      early event in the pathogenesis of atherosclerosis. To understand the mechanism
      by which oxidized LDL (oxLDL) causes dysfunction in endothelial cells, human
      umbilical vein endothelial cells (HUVEC) were exposed to oxLDL at a concentration
      that induces cellular dysfunction, and proteomic analysis was carried out,
      together with the analysis of cellular lipid peroxidation products. Time
      dependent accumulation of 7-ketocholesterol and the progression of oxidative
      modification of peroxiredoxin 2 were observed, together with the suppression of
      cell proliferation. Proteomic analysis using two-dimensional gel electrophoresis
      (2-D gel) revealed that nucleophosmin, stathmin, and nucleolin were
      differentially expressed after exposure to oxLDL. Both 2-D gel and western blot
      analyses revealed that (1) nucleophosmin was dephosphorylated in a time-dependent
      manner; (2) stathmin was transiently phosphorylated at 6 h, and the
      unphosphorylated form was continuously down-regulated; and (3) nucleolin was
      identified as a 20-kDa fragment and a 76-kDa form, which were down-regulated.
      These observations suggest that the exposure of HUVEC to oxLDL results in the
      suppression of cell proliferation, which is ascribed to protein modification
      and/or altered expression of nucleophosmin, stathmin, and nucleolin under these
      oxidative stress conditions.

PMID- 16298865
TI  - Free radical scavenging and hepatoprotective actions of Quercus aliena acorn
      extract against CCl4-induced liver.
AB  - In the present study, we investigated the protective effect of Quercus aliena
      acorn extracts against CCl4-induced hepatotoxicity in rats, and the mechanism
      underlying the protective effects. Aqueous extracts of Quercus aliena acorn had
      higher superoxide radical scavenging activity than other types of extracts. The
      Quercus aliena acorn extracts displayed dose-dependent superoxide radical
      scavenging activity (IC50 = 4.92 microg/ml), as assayed by the electron spin
      resonance (ESR) spin-trapping technique. Pretreatment with Quercus aliena acorn
      extracts reduced the increase in serum aspartate aminotransferase (AST) and serum
      alanine aminotransferase (ALT) levels. The hepatoprotective action was confirmed
      by histological observation. The aqueous extracts reversed CCl4-induced liver
      injury and had an antioxidant action in assays of FeCl2- ascorbic acid induced
      lipid peroxidation in rats. Expression of cytochrome P450 2E1 (CYP2E1) mRNA, as
      measured by RT-PCR, was significantly decreased in the livers of Quercus aliena
      acorn-pretreated rats compared with the livers of the control group. These
      results suggest that the hepatoprotective effects of Quercus aliena acorn extract
      are related to its antioxidative activity and effect on the expression of CYP2E1.

PMID- 16298866
TI  - Accumulation of the hydroxyl free radical markers meta-, ortho-tyrosine and DOPA
      in cataractous lenses is accompanied by a lower protein and phenylalanine content
      of the water-soluble phase.
AB  - Post-translational modifications of lens proteins play a crucial role in the
      formation of cataract during ageing. The aim of our study was to analyze protein
      composition of the cataractous lenses by electrophoretic and high-performance
      liquid chromatographic (HPLC) methods. Samples were obtained after extracapsular
      cataract surgery performed by phacoemulsification technique from cataract
      patients with type 2 diabetes mellitus (DM CAT, n = 22) and cataract patients
      without diabetes (non-DM CAT, n = 20), while non-diabetic non-cataractous lenses
      obtained from cadaver eyes served as controls (CONTR, n = 17). Lens fragments
      were derived from the surgical medium by centrifugation. Samples were homogenized
      in a buffered medium containing protease inhibitor. Soluble and insoluble protein
      fractions were separated by centrifugation. The electrophoretic studies were
      performed according to Laemmli on equal amounts of proteins and were followed by
      silver intensification. Oxidized amino acid and Phe content of the samples were
      also analyzed by HPLC following acid hydrolysis of proteins. Our results showed
      that soluble proteins represented a significantly lower portion of the total
      protein content in cataractous lenses in comparison with the control group
      (CONTR, 71.25%; non-DM CAT, 32.00%; DM CAT, 33.15%; p < 0.05 vs CONTR for both).
      Among the proteins, the crystallin-like proteins with low-molecular weight can be
      found both in the soluble and insoluble fractions, and high-molecular weight
      aggregates were found mainly in the total homogenates. In our HPLC analysis,
      oxidatively modified derivatives of phenylalanine were detected in cataractous
      samples. We found higher levels of m-Tyr, o-Tyr and DOPA in the total homogenates
      of cataractous samples compared to the supernatants. In all three groups, the
      median Phe/protein ratio of the total homogenates was also higher than that of
      the supernatants (total homogenates vs supernatants, in the CONTR group 1102 vs
      633 micromol/g, in the DM CAT group 1187 vs 382 micromol/g and in the non-DM CAT
      group 967 vs 252 micromol/g; p < 0.05 for all). In our study we found that
      oxidized amino acids accumulate in cataractous lenses, regardless of the origin
      of the cataract. The accumulation of the oxidized amino acids probably results
      from oxidation of Phe residues of the non-water soluble lens proteins. We found
      the presence of high-molecular weight protein aggregates in cataractous total
      homogenates, and a decrease of protein concentration in the water-soluble phase
      of cataractous lenses. The oxidation of lens proteins and the oxidative
      modification of Phe residues in key positions may lead to an altered interaction
      between protein and water molecules and thus contribute to lens opacification.

PMID- 16298864
TI  - Association of CAT polymorphisms with catalase activity and exposure to
      environmental oxidative stimuli.
AB  - We tested the hypotheses that catalase activity is modified by CAT single
      nucleotide polymorphisms (SNPs) (-262;-844), and by their interactions with
      oxidant exposures (coal dusts, smoking), lymphotoxin alpha (LTA, NcoI) and tumor
      necrosis factor (TNF, -308) in 196 miners. Erythrocyte catalase, superoxide
      dismutase, and glutathione peroxidase activities were measured. The CAT -262 SNP
      was related to lower catalase activity (104, 87 and 72 k/g hemoglobin for CC, CT
      and TT, respectively, p < 0.0001). Regardless of CAT SNPs, the LTA NcoI but not
      the TNF-308 SNP was associated with catalase activity (p = 0.04 and p = 0.8). CAT
      -262 T carriers were less frequent in highly exposed miners (OR = 0.39 [0.20
      0.78], p = 0.007). In CAT -262 T carriers only, catalase activity decreased with
      high dust exposure (p = 0.01). Haplotype analyses (combined CAT SNPs) confirm
      these results. Results show that CAT -262 and LTA NcoI SNPs, and interaction with
      coal dust exposure, influenced catalase activity.

PMID- 16298867
TI  - Novel bioassay system for evaluating anti-oxidative activities of food items: use
      of basolateral media from differentiated Caco-2 cells.
AB  - Reactive oxygen and nitrogen species, including superoxide and nitric oxide (NO),
      are known to be mediators of oxidative stress and play pivotal roles in the onset
      of numerous life style-related diseases. While a number of studies have shown
      that naturally occurring anti-oxidants may be applicable for prevention and
      therapy for those diseases, most in vitro anti-oxidation tests reported have not
      provided significant insight into the absorption efficiency or metabolism of
      dietary anti-oxidants in the gastrointestinal tract. In the present study, we
      established a novel assay system by focusing on the bioconversion of food
      constituents using differentiated Caco-2 cells as a model of human intestinal
      epithelial cells. Various fresh food preparations [ginger, garlic, shimeji
      (Hypsizigus marmoreus), onion, carrot] were added to the apical side of
      differentiated Caco-2 monolayers. After incubation, the medium was recovered and
      tested for its inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)
      induced generation in differentiated HL-60 cells, and on combined
      lipopolysaccharide (LPS)- and interferon (IFN)-gamma -induced NO generation in
      RAW 264.7 macrophages. The garlic preparation (25% v/v) basolateral medium
      abolished generation without any cytotoxicity toward HL-60 cells, though it was
      cytotoxic to Caco-2 cells. In the NO generation tests, all of the food
      preparations showed notable inhibitory activity, while the garlic preparation (5%
      v/v) basolateral medium inhibited NO generation with substantial cytotoxicity
      toward RAW 264.7 cells. Interestingly, the carrot preparation (1% v/v)
      basolateral medium inhibited NO generation in both a concentration- and time
      dependent manner without any cytotoxicity toward RAW 264.7 or Caco-2 cells, and
      its activities were higher than those of the carrot preparation alone (1% v/v).
      Our results indicate that the present assay system is appropriate and reliable
      for determination of the anti-oxidative efficacy of dietary phytochemicals in
      vivo.

PMID- 16298868
TI  - Protective effects of ellagic and chlorogenic acids against oxidative stress in
      PC12 cells.
AB  - Following exposure of differentiated neuronal PC12 cells to either t-BHP,
      hydrogen peroxide (H2O2) or FeSO4 various kinds of reactive oxygen species (ROS)
      are generated leading to oxidative injury. The protective effects of two plant
      polyphenols, ellagic (EC) and chlorogenic acid (CGA), as well as of two
      metabolites, caffeic acid (CA) and ferulic acid (FA), were investigated in
      preincubation and coincubation experiments with respect to the following
      parameters: prevention of cell death, GSH depletion, lipid peroxidation and ROS
      formation. The polyphenols more efficiently suppressed cytotoxicity and loss of
      GSH caused by peroxides than by iron, particularly in preincubation. Lipid
      peroxidation which increased much stronger in response to FeSO4 was counteracted
      completely by the polyphenols. In case of iron, however, only coincubation was
      effective. EA and CGA and the metabolites CA and FA showed excellent elimination
      of ROS induced by all stressors. These findings suggest that two dietary
      antioxidants, EA and CGA, may have protective properties against oxidative stress
      induced in CNS.

PMID- 16298869
TI  - Hypoxia-induced micronucleus formation in mice.
AB  - The effect of hypoxia on micronucleus formation in mice was evaluated using
      special "shoebox" cages containing a silicone rubber membrane that effectively
      excludes the replacement of cage oxygen as it is spent by group-housed mice. In
      five separate trials using between 13 and 17 mice per cage, the oxygen level in
      the cage was reduced from the normal 21% to an average of 7.5% in 3-7 days.
      Compared to control animals, which exhibited a spontaneous micronuclei (MN)
      frequency of 0.08%, mice living under hypoxic conditions exhibited a
      statistically significant (p < or = 0.01) elevation in MN frequency of 0.15%.
      These findings may be relevant to in vivo studies in which drug or chemical
      treatment results in hypoactivity or complete sedation accompanied by varying
      degrees of hypoxia. It is proposed that structurally unexpected positive
      clastogenicity findings in animals exposed to these conditions may be due to
      hypoxia rather than to drug-DNA interaction. The likely mechanistic basis for
      this effect, decreased fidelity of cell division under conditions of elevated
      erythropoiesis, is discussed.

PMID- 16298870
TI  - Acute, subchronic, and mutagenicity studies with norbornene fluoroalcohol.
AB  - The object of this study was to evaluate the toxicity of norbornene fluoroalcohol
      (NBFOH), which is used as an intermediate in the production of fluorinated
      monomers and polymers. NBFOH was evaluated for acute oral, dermal, and inhalation
      toxicity, dermal sensitization using the Local Lymph Node Assay (LLNA),
      mutagenesis by the Ames assay, and subchronic toxicity in a 4-week inhalation rat
      study. NBFOH demonstrated slight acute toxicity in oral, dermal, and inhalation
      studies. Approximate lethal doses of 3400 and > 5000 mg/kg for the oral and
      dermal routes, respectively, and an approximate lethal concentration of 4300
      mg/m(3) were determined. NBFOH demonstrated moderate skin irritation, was a
      severe eye irritant, produced dermal sensitization, but did not cause bacterial
      mutagenicity either in the presence or absence of S9 activation. Male and female
      rats were exposed nose only to airborne NBFOH at levels of 0, 410, 1400, and 1500
      mg/m(3), 6 h/day, 5 days/week for 4 weeks with clinical and histopathology
      specimens collected 1 day after the final exposure. Due to the vapor pressure of
      NBFOH, the 1500 mg/m(3) atmosphere was 27% aerosol and 73% vapor; the 1400
      mg/m(3) atmosphere was 5% aerosol and 95% vapor, and the 410 mg/m(3) level was
      only vapor. No test substance-related mortality or clinical signs of toxicity
      were observed over the course of the study, and male rats demonstrated
      significant weight loss and decreased food consumption at 1400 mg/m(3). Male rats
      from the 1500 mg/m(3) group demonstrated an 11% increase in prothrombin time that
      was significantly higher than the control value. Examination of fluoride in the
      urine did not demonstrate a concentration-response relationship, with minimal
      elevations observed in male rats at all exposure levels and sporadic increases in
      females. Both male and female rats exposed to 1400 mg/m(3) or greater had
      squamous metaplasia of the laryngeal mucosa and degeneration of the nasal
      olfactory and respiratory mucosa. Based on the above findings, NBFOH demonstrates
      the potential to produce allergic contact dermatitis, and subchronic inhalation
      studies indicate a no-observed-adverse-effect-level (NOAEL) of 410 mg/m(3).

PMID- 16298871
TI  - Hemolytic effects of sodium selenite and mercuric chloride in human blood.
AB  - Many works have reported the interaction between selenium and mercury in the
      mammalian body and that chalcogen seems to have a protective effect against
      mercury toxicity. The aim of this study was to investigate the hemolytic effects
      of sodium selenite and/or mercuric chloride in human blood under in vitro
      conditions. For this, total venous blood from healthy subjects (males and
      females) was heparinized and incubated at 37 degrees C for 90 min with different
      concentrations of sodium selenite and/or mercuric chloride. The hemolytic effects
      of compounds were evaluated by measuring plasma hemoglobin concentration after
      centrifugation. In addition, 2-thiobarbituric acid reactive substances (TBARS)
      from plasma and erythrocytes, as well as erythrocyte nonprotein thiols (NPSH),
      were also evaluated in order to investigate molecular mechanisms related to
      selenite- or mercury-induced hemolysis. Mercuric chloride and sodium selenite,
      alone (400 microM), promoted a small in vitro hemolytic effect in human
      erythrocytes. However, when blood was exposed to both compounds (200 microM of
      each), there was an extremely high synergistic hemolytic effect. The exposure of
      blood to sodium selenite (400 microM), mercuric chloride (400 microM), and both
      compounds (200 microM each) did not alter erythrocyte TBARS levels. Sodium
      selenite presented a high oxidant effect toward erythrocyte NPSH; however, this
      effect was inhibited by mercuric chloride. The current results point to a
      synergistic hemolytic effect of sodium selenite and mercuric chloride in human
      blood, suggesting new understanding on the selenium-mercury antagonism. Moreover,
      this observed hemolysis seems to be not related to lipoperoxidation or thiol
      depletion.

PMID- 16298872
TI  - Combined treatment potentiates the developmental toxicity of ibuprofen and
      acetazolamide in rats.
AB  - Aspirin (ASA), an irreversible cyclooxygenase (COX) inhibitor, induces
      ventricular septal defect (VSD) and diaphragmatic hernia (DH) in rat fetuses when
      administered on gestation days (GDs) 9-10, a critical period for cardiovascular
      (CV) and midline development. Evaluation of a spectrum of nonsteroidal
      antiinflammatory drugs (NSAIDs; reversible COX inhibitors) showed that while some
      NSAIDs induced VSD in rats, none of the NSAIDs evaluated produced DH. In addition
      to inhibiting COX, ASA also inhibits carbonic anhydrase. The purpose of this
      study was to determine whether concurrent inhibition of COX and carbonic
      anhydrase would produce a teratogenic profile that includes both VSD and DH. To
      inhibit both COX and carbonic anhydrase, ibuprofen (COX inhibitor) and
      acetazolamide (carbonic anhydrase inhibitor) were coadministered on GDs 9-10.
      Groups of 20 female Crl:CD(SD)IGS BR rats were given either 300 mg kg(-1) day(-1)
      ibuprofen, 1000 mg kg(-1) day(-1) acetazolamide, or both (combination of
      ibuprofen and acetazolamide). Fetuses were evaluated on GD 21 for external and
      visceral development. Ibuprofen induced VSD in 3.7% of fetuses per litter; no
      defects in appendicular skeletal development were noted. Acetazolamide induced
      VSD in 5.9% of the fetuses per litter and appendicular defects in 41% of the
      fetuses per litter. Coadministration of ibuprofen and acetazolamide produced VSD
      in 18.7% of the fetuses per litter and appendicular defects in 77% of the fetuses
      per litter; however, there were no DH. Therefore, while concurrent inhibition of
      COX and carbonic anhydrase did not produce DH, potentiation was noted for the
      induction of VSD and appendicular anomalies.

PMID- 16298873
TI  - Effects of miglyol 812 on rats after 4 weeks of gavage as compared with
      methylcellulose/tween 80.
AB  - Miglyol 812 is a medium-chain triglyceride used in toxicology studies as an
      excipient to improve test compound solubility/absorption. As part of a larger
      toxicology study, 15 Wistar Han IGS rats/sex/group were dosed by oral gavage for
      4 weeks with 10 mL kg(-1) day(-1) of 100% Miglyol 812 or 0.5%
      methylcellulose/0.1% Tween 80 in water (MC-T) followed by 4 weeks without
      treatment to evaluate the potential effects of this excipient in long-term
      toxicology studies relative to a traditional excipient such as MC-T. Clinical
      signs evident during the dosing phase included soft and/or mucoid stool in 12/15
      males and 11/15 females treated with Miglyol 812 but in no animals treated with
      MC-T. Animals treated with Miglyol 812 had a 6-7% statistically significant
      reduction in body weight gain as compared to MC-T-treated animals. Statistically
      significant changes in clinical chemistry parameters as compared to MC-T included
      decreased blood urea nitrogen (50% and 29% in males and females, respectively),
      increased cholesterol (1.6-fold and 1.5-fold in males and females, respectively),
      decreased total protein (6% and 8% in males and females, respectively), decreased
      globulins (15% and 11% in males and females, respectively), and increased
      triglycerides (2.8-fold and 1.7-fold in males and females, respectively).
      Absolute and relative thymic weights decreased 28% and 24%, respectively, in
      males, and 18% and 17%, respectively, in females without histological
      alterations. Histopathology revealed increased alveolar histiocytosis with focal
      interstitial inflammation in lungs in 5/10 males and 7/10 females treated with
      Miglyol 812 compared to only 1/10 males and 1/10 females treated with MC-T. All
      effects were reversible during the recovery period. Results of this study
      indicate that 100% miglyol 812 produces reversible gastrointestinal effects and
      decreases in body weight gains along with changes in several serum chemistry
      parameters. Therefore, it should not be considered innocuous when delivered by
      oral gavage in long-term rodent toxicology studies.

PMID- 16298874
TI  - Effects of some antibiotics on activity of glucose-6-phosphate dehydrogenase from
      human erythrocytes in vitro and effect of isepamicin sulfate on activities of
      antioxidant enzymes in rat erythrocytes.
AB  - The purpose of this study was to investigate effects of some antibiotics on
      glucose-6-phosphate dehydrogenase (G6PD), antioxidant enzymes, and
      malondialdehyde (MDA). Initially, for in vitro studies, G6PD was purified from
      human erythrocyte, 9811-fold in a yield of 42.4% by using ammonium sulfate
      precipitation and 2',5' ADP-Sepharose 4B affinity gel. The purified enzyme showed
      a single band on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE). The effects of four different antibiotics (isepamicin sulfate, meropenem,
      chloramphenicol, and thiamphenicol glisinat hydrochloride) were investigated on
      the purified enzyme. K(i) value and type of inhibition were determined by means
      of Lineweaver-Burk graphs and regression analysis graphs. Isepamicin sulfate
      inhibited the enzyme activity (I(50) value, 2.1 mM; K(i) value, 1.7 mM), whereas
      thiamphenicol glisinat hydrochloride activated the G6PD dose dependently. Other
      drugs showed no inhibition and activation effect. In addition, the effects of
      isepamicin sulfate on the activities of G6PD, glutathione reductase (GR),
      superoxide dismutases (SOD), glutathione peroxidase (GPx), catalase (CAT), and
      glutathione S-transferase (GST) and MDA concentrations were examined in Sprague
      Dawley rat erythrocytes in vivo. A marked alteration in the activities of these
      enzymes and MDA levels may be the result of oxidative stress in the rats
      receiving isepamicin sulfate.

PMID- 16298875
TI  - Toxicological screening for the effects of short-term exposure of sidestream
      cigarette smoke on angiogenesis.
AB  - Angiogenesis is a fundamental process that ensures adequate metabolic supply to
      tissues in numerous biological and pathological states, including tumorigenesis.
      Cigarette smoking causes numerous adverse effects, some of which are associated
      with disruption of the normal process of angiogenesis. It is believed that
      sidestream cigarette smoke severely affects different components that help in the
      normal process of angiogenesis. Sidestream cigarette smoke is composed primarily
      of smoke that emanates from the burning end of a cigarette, and contaminants that
      diffuse through the cigarette paper. The aim of the current study was to
      ascertain the toxicological effects of different sidestream cigarette smoke
      solutions (SSCSS) on angiogenesis by using chicken chorioallantoic membrane (CAM)
      assay. Decrease in total vascular area, diameter of secondary and tertiary blood
      vessels, cell proliferation, migration of blood vessels toward ectoderm, and
      number of capillary plexuses formation was observed by application of SSCSS.
      Scanning microscopy also revealed deviation in pattern formed by the major
      capillary plexuses and the fibrillar elements of the mesoderm SSCSS in treated
      CAMs. It is concluded that SSCSS may hinder the normal process of angiogenesis
      resulting in abnormal blood supply to tissues and decreased repair and
      remodeling, which are common problems among smoke-exposed individuals. Further
      study is required to delineate the effects of different chemicals in SSCSS on
      angiogenesis.

PMID- 16298876
TI  - Antimalarials inhibit human erythrocyte membrane acetylcholinesterase.
AB  - The current study examined the ability of antimalarials chloroquine (CQ),
      primaquine (PQ), and quinine (Q) to inhibit human erythrocyte membrane
      acetylcholinesterase (AChE) and the mechanisms underlying their inhibitory
      action. CQ was found to be the most effective inhibitor of the enzyme followed by
      PQ and Q. The concentrations required to obtain 33% inhibition (IC(33)) for CQ
      and PQ were 22 and 38 microM, respectively, whereas that for Q was 3.2 mM. The
      concentrations required to obtain 67% inhibition (IC(67)) were about 9 and 7
      times higher for CQ and PQ, whereas that for Q was only about 2.5 times higher.
      Hill plot analysis revealed that CQ shows de-binding above 40 microM. The two
      kinetic components of AChE were inhibited by the three antimalarials, and the
      inhibition was of mixed type. Increasing concentrations of antimalarials caused
      progressive decrease in the V(max) of both components. IC(33) concentrations
      resulted in 1.6- to 6-fold increase in K(m) of both the components while IC(67)
      concentration caused 2.8- to 13-fold increases in K(m) with maximum effect being
      seen with Q. The K(i) values were lowest for CQ suggesting that it was the most
      potent inhibitor; these values were 3.3 and 60 times higher for PQ and Q.
      Antimalarials represent the bifunctional compounds that possess anti-inflammatory
      properties and also inhibit cholinesterases. The results of our studies suggest
      that 4-aminoquinoline-based antimalarials like CQ and hydroxychloroquine, which
      are both potent anti-inflammatory agents and inhibitors of cholinesterases, may
      have potential use as the most effective neuroprotective agents against amyloid
      beta-peptide (Abeta) neurotoxicity in Alzheimer's disease.

PMID- 16298877
TI  - Protective effects of glurenorm (gliquidone) treatment on the liver injury of
      experimental diabetes.
AB  - Oxidative stress plays an important role in chronic complications of diabetes
      mellitus, and hence the regulation of free radicals is essential in the treatment
      of diabetes. The aim of the current study is to investigate the effect of
      glurenorm (10 mg/kg) on liver tissue in experimental diabetes. Diabetes was
      induced by intraperitoneal injection of 65 mg/kg streptozotocin. Glurenorm was
      administered to one diabetic and one control group separately, from days 14 to
      42. On day 42, cardiac blood samples and liver tissue were taken from each rat.
      In diabetic rats, blood glucose, serum alkaline phosphatase and serum amino
      transferase activities, serum uric acid, serum sodium and potassium levels, liver
      nonenzymatic glycosylation, and lipid peroxidation increased, whereas body weight
      and liver glutathione levels decreased. The diabetic group given glurenorm blood
      glucose, serum alkaline phosphatase and aminotransferase activities, serum uric
      acid, sodium and potassium, liver nonenzymatic glycosylation, and lipid
      peroxidation levels decreased, and liver glutathione levels increased. As a
      result of all the biochemical findings obtained, it was concluded that glurenorm
      has a protective effect on damage of liver of streptozotocin-induced diabetes in
      rats.

PMID- 16298882
TI  - Visual lateralisation, form preferences, and secondary imprinting in the domestic
      chick.
AB  - Newly hatched chicks (Exp. 1) were exposed to an imprinting object of a certain
      shape (sphere/cylinder) on Day 1 (primary imprinting) and then to a different
      shaped object (cylinder/sphere) on Day 2 (secondary imprinting). They were tested
      on Day 3 for preferences between primary and secondary imprinting objects in
      binocular and monocular conditions. Right-eyed males, but not females, showed
      relatively stronger preferences for the primary imprinting object than left-eyed
      males; however, the asymmetry was modulated by a spontaneous preference for the
      sphere. In Experiment 2, a more traditional imprinting paradigm was used: chicks
      were exposed to the same object for the first 2 days, and on Day 3 underwent a
      free-choice test between the imprinting object (sphere/cylinder) and a novel one
      (cylinder/sphere). Results showed that no asymmetries in the use of eyes were
      apparent, only a general preference for the sphere. In Experiment 3 chicks were
      exposed, as in Experiment 1, to a primary (Day 1) and a secondary (Day 2)
      imprinting object; on Day 3 they were exposed to both objects simultaneously;
      they were also tested for preferences for the two stimuli on Day 4. Left- and
      right-eyed chicks showed different choice, with the latter preferring the
      cylinder, thus showing that the eye-asymmetry was in some way peculiar to the
      secondary imprinting procedure.

PMID- 16298878
TI  - In vivo micronucleus assay and GST activity in assessing genotoxicity of
      plumbagin in Swiss albino mice.
AB  - Information available on the mutagenicity of a large number of indigenous drugs
      commonly employed in the Siddha and Ayurveda systems of medicine is scanty. In
      this context, the current investigation on plumbagin, 5-hydroxy-2methyl-1,4
      napthoquinone, an active principle in the roots of Plumbago zeylanica used in
      Siddha and Ayurveda for various ailments, was carried out; 16 mg/kg b.w. (LD(50))
      was fixed as the maximum dose. Subsequent dose levels were fixed as 50% and 25%
      of LD(50) amounting to 8 mg and 4 mg/kg b.w., respectively, and given orally for
      5 consecutive days in 1% Carboxyl Methyl Cellulose (CMC) to Swiss albino mice
      weighing 25-30 g. The micronucleus assay was done in mouse bone marrow. Plumbagin
      was found to induce micronuclei at all the doses studied (4 mg/kg, 8 mg/kg, 16
      mg/kg b.w.), and it proves to be toxic to bone marrow cells of Swiss albino mice.
      Animal treated with cyclophosphamide (40 mg/kg b.w.) served as positive control.
      In addition, glutathione S-transferase (GST) activity was observed in control,
      plumbagin (4 mg, 8 mg, 16 mg/kg b.w., respectively), and genotoxin-treated
      experimental group of animals. No significant change in GST activity was observed
      with plumbagin dose of 4 mg/kg b.w., whereas GST activity was significantly
      inhibited by higher doses of plumbagin (8 mg and 16 mg/kg b.w.) and
      cyclophosphamide.

PMID- 16298883
TI  - Magical ideation and its relation to lateral preference.
AB  - Schizophrenia and schizotypal personality have been linked to sinistrality as
      well as ambidextrality. The current study clarifies the relation between
      laterality and schizotypal personality by administering a battery of laterality
      questionnaires to measure hand, eye, ear, and foot preference in a group of 933
      university students. To determine whether the relationship between schizotypy and
      laterality is limited to self-report measures, performance asymmetries between
      the hands were measured with tapping rate. There was no difference between
      dextrals and sinistrals in schizotypal personality, as indexed by the Magical
      Ideation (MI) scale. MI was higher, however, for individuals with a weak
      preference for either hand or eye compared to those with a strong dominance. In
      addition, individuals inconsistent in their lateral preference across modalities
      showed higher MI scores. Performance asymmetries had no effect on MI scores. This
      lack of effect was attributed to the inability of performance measures, such as
      tapping rate, to identify ambidextrals. The results support research linking
      schizotypal personality to ambidextrality and weak cerebral dominance and
      demonstrate that the association extends to modalities other than hand
      preference.

PMID- 16298884
TI  - Constant and variable aspects of the dichotic listening right-ear advantage: a
      comparison of standard and signal detection tasks.
AB  - The study was designed to disentangle perceptual and attentional components of
      the dichotic listening right-ear advantage (REA). A total of 120 normal adults
      (108 right-handers and 12 left-handers) were administered the Halwes Fused
      Dichotic Words Test (FDWT) under standard conditions, which entail a forced
      choice response format and no attention instructions. Two weeks later, the same
      stimuli were administered in a signal detection format with varied attention
      instructions (left, right, and equally divided). The standard task yielded the
      expected REA. The signal detection task yielded an REA for detection of targets
      that remained invariant across attention conditions. In contrast, ear asymmetry
      for localisation of targets varied with attention instructions. The REA on the
      standard task was correlated with the asymmetry of target detection (r = .57) on
      the signal detection task but not with the asymmetry of localisation or response
      bias. Ear asymmetry on the standard test seems to reflect an early stage of
      processing that is not altered by shifts of attention. Volitional shifts of
      attention influence the localisation of targets, but this component of signal
      processing is unrelated to the REA obtained on the standard test.

PMID- 16298886
TI  - Hemispheric activation and interaction: past activity affects future performance.
AB  - Previous studies have shown that when hemispheric activation is modulated by a
      lateralised task performed concurrently with a second task, performance in the
      second task is affected by the side of the more active hemisphere. This effect is
      thought to be produced by competition for limited resources required to complete
      the two tasks and/or by a greater allocation of attention to the hemifield
      contralateral to the more active hemisphere. Little is known on how task
      performance is affected by the pattern of activation in the two cerebral
      hemispheres before a target task is conducted. The present study investigated how
      manipulation of hemispheric activity influenced performance of a non-lateralised
      task (letter matching). Greater left hemisphere activity interfered most with
      performance of the letter- matching task and was more pronounced in the early
      learning stage. Male participants were most affected by this effect. The results
      are discussed in relation to hemispheric interaction, functional lateralisation,
      and allocation of attention.

PMID- 16298885
TI  - Attention, reliability, and validity of perceptual asymmetries in the fused
      dichotic words test.
AB  - The present experiment investigated the claim that the fused dichotic words test
      (FDWT) is affected minimally by attentional factors. A total of 40 right-handed
      undergraduate students were randomly assigned to either a free recall or
      exogenous cueing condition. In the free recall condition, participants circled on
      a response sheet the word corresponding to the percept they heard for each trial.
      In the exogenous cueing condition, a lateralised tone cue was presented with a
      stimulus onset asynchrony (SOA) of either 150 or 450 ms. Participants responded
      by circling the word presented to the ear where the tone sounded. Results of the
      free recall condition showed the expected large right ear advantage (REA). In the
      exogenous cueing condition, the significant SOA by ear of presentation
      interaction predicted by an attentional explanation of perceptual asymmetries was
      obtained. Specifically, the REA obtained at the 150 ms SOA was reduced at the 450
      ms SOA for both correct responses and intrusions. These findings suggest that,
      contrary to claims conveyed in the literature, the FDWT is subject to the
      influences of attention. This supports the claim that the large and reliable
      laterality effects obtained with the fused dichotic words test are due in part to
      a consistent attentional bias.

PMID- 16298888
TI  - Study-time effect on free recall within and out of context.
AB  - Three experiments examined whether or not the study-time effect, which was
      observed when recall took place in the original environmental context, was
      eliminated or markedly diminished when recall took place in a different
      environmental context. A total of 456 undergraduates studied a list of words for
      either a short or long study time before receiving an oral free recall test under
      conditions where the original environmental context was or was not reinstated.
      Environmental context was manipulated by the combination of physical features of
      the room, subsidiary task, and experimenter. Inter-item association was minimised
      in Experiment 1, and free recall performance was measured independently of inter
      item association in Experiments 2 and 3. The results were: (1) a greater study
      time effect was found when the original context was reinstated than when it was
      not reinstated, and (2) the study-time effect disappeared when neither contextual
      nor inter-item associative cues were available. The results suggest that
      environmental context is involved in the production of the study-time effect.

PMID- 16298889
TI  - A novel study: investigating the structure of narrative and autobiographical
      memories.
AB  - In two experiments we assessed the degree to which memory for events are similar
      or differ depending on whether they were narrative or autobiographical events.
      Consistent with previous research on autobiographical memory, memories for events
      captured the sequential order of events. However, in contrast to autobiographical
      memory research, ratings of importance did not appear to be related to retrieval
      speed. An analysis of causal connectivity of the recalled events was
      significantly related to retrieval speed. Issues of narrative comprehension and
      memory, autobiographical memory, and their overlap are discussed.

PMID- 16298890
TI  - The incidence of false memories in native and non-native speakers.
AB  - The current study consisted of four experiments that utilised a novel approach to
      investigating false memories. Each of the experiments in the current study
      investigated individuals with varying experience with different languages.
      Experiment 1 tested participants in both their native and secondary languages as
      well as monolingual English speakers, while Experiment 2 assessed native Spanish
      speakers using both English and Spanish associative lists. Experiment 3 examined
      the illusory memories in monolingual Spanish speakers in both English and
      Spanish, while Experiment 4 investigated false memories in monolingual English
      speakers in both English and Spanish. Results indicated that memory for list
      items and critical lures was greatest when the lists were presented in the
      participants' primary language. Results can be explained by either activation
      based or fuzzy-trace theories.

PMID- 16298891
TI  - Autobiographical memory in middle childhood: recollections of the recent and
      distant past.
AB  - To address the question of whether memories from early childhood survive into
      later childhood, participants visited the laboratory at age 3 and again at 7, 8,
      or 9. At age 3, each talked with a parent about six events; at the later age each
      child talked with a researcher about four of these distant events as well as two
      more recent events. School-aged children recalled fewer than half of the distant
      events introduced. Further, the proportion of distant events recalled was
      negatively correlated with age. Those distant events that were recalled, however,
      were recounted in an accurate, detailed manner. Importantly, reports of distant
      events did not reflect the full extent of children's narrative ability. Reports
      of recent events were more coherent and included twice the detail. Implications
      for existing interpretations of autobiographical memory and childhood amnesia are
      discussed, and the need for further research employing innovative methods is
      emphasised.

PMID- 16298892
TI  - The end point effect in autobiographical memory: more than a calendar is needed.
AB  - The end point effect, an increased frequency of memories from the start and end
      of a period, may be due to internalised calendar representations or narrative
      structures. Differential predictions derived from these theories were tested in 3
      studies. In Study 1, 104 students recalled 5 memories from a relationship. In
      Study 2, 106 students recalled 5 memories from their first term and in Study 3,
      89 students recalled 3 positive and 3 negative memories from their first term. In
      all three studies memories were rated on phenomenology, encoding variables and
      rehearsal. All three studies replicated the endpoint effect, with Study 3 showing
      a stronger effect for positive memories. The studies showed higher rating for end
      point memories on phenomenology (Study 1), encoding variables (Studies 1 and 2)
      and rehearsal (Study 1). Generally, the results support the narrative theory and
      this is discussed in relation to broader theories of autobiographical memory.

PMID- 16298893
TI  - Can test list context manipulations improve recognition accuracy in the DRM
      paradigm?
AB  - Only test-based manipulations can be used to help people distinguish accurate
      from false memories once events have been encoded. In two experiments we examined
      how the type of studied words (weak vs strong associates, or less vs more
      memorable associates) and nonstudied lure words (related vs unrelated lures) on
      the test list affect recognition accuracy in the Deese-Roediger-McDermott
      paradigm. False recognition of critical lures decreased substantially in the
      related-lure context, but so did correct recognition of studied words. False
      recognition was little affected by the studied-word manipulations. In general,
      participants claimed to recognise critical lures as often as weak associates or
      less memorable studied words but less often than either strong associates or more
      memorable studied words. The test-list context affected how participants
      classified their recognition experiences but it did not systematically change
      their overall memory accuracy.

PMID- 16298894
TI  - Priming involuntary autobiographical memories.
AB  - Involuntary autobiographical memories occur frequently in daily life and are
      usually triggered by cues in one's environment. This study investigated the
      possibility that priming plays a role in the production of involuntary memories.
      In Study 1, participants recorded their involuntary memories in a diary for 14
      days and then completed a questionnaire assessing their cognitive activity during
      the recording period. Participants indicating frequent thought about significant
      others on the questionnaire showed significantly more involuntary memories
      related to such individuals than a control group. In Studies 2 and 3,
      participants recorded their involuntary memories in diaries for 14 days and were
      primed with recall sessions in the laboratory during that period (recalling
      episodes from high school, Study 1, the past year, or ages 13-16, Studies 2 & 3).
      The results of both studies showed significant priming effects in the involuntary
      memories of participants for all of the periods primed. The possibility that
      priming plays a significant role in the daily production of involuntary memories
      is discussed.

PMID- 16298895
TI  - The effects of different decalcification protocols on TUNEL and general cartilage
      staining.
AB  - Apoptosis is characterized by DNA strand breaks with a 3'-OH terminus, which are
      analyzed by terminal deoxy(d)-UTP nick end labeling (TUNEL). Proteinase K
      digestion is thought to be an essential step in the TUNEL procedure. The effects
      of decalcifying reagents on general staining and the TUNEL assay for cartilage
      sections are largely unknown. The effects of these reagents on retention and
      integrity of DNA in chondrocytes have not been described until now. We evaluated
      the effects of various decalcifying solutions, including 10% EDTA, 10% citric
      acid, 5% trichloroacetic acid, 5% acetic acid and a commercial hydrochloric acid
      based reagent, on general cartilage staining and the TUNEL assay for cartilage.
      The effects of proteinase K on nucleus preservation were also examined.
      Decalcification with 10% EDTA gave the best result for general cartilage
      staining. Chondrocyte DNA was retained and intact after using this reagent.
      Decalcification with 10% EDTA is also the safest method of decalcification if the
      TUNEL assay is applied to cartilage. Proteinase K digestion may have adverse
      effects on nucleus preservation in cartilage. Awareness of these effects is
      important whenever the TUNEL assay is applied.

PMID- 16298896
TI  - Preparation of soybean seed samples for FT-IR microspectroscopy.
AB  - Typical preparation of seed samples for infrared (IR) microspectroscopy involves
      imbibition of the seed for varying time periods followed by cryosectioning.
      Imbibition, however, may initiate germination even at 4 degrees C with associated
      changes in the chemistry of the sample. We have found that it is possible to
      section seeds that are sufficiently hard, such as soybeans, on a standard
      laboratory microtome without imbibition. The use of dry sectioning of unimbibed
      seeds is reported here, as well as a comparison of different mounting media and
      modes of analysis. Glycerol, Tissue-Tek, and ethanol were used as mounting media,
      and the quality of the resulting spectra was assessed. Ethanol was the preferred
      mountant, because it dried quickly with no residue and thus did not interfere
      with the spectrum of interest. Analysis in transmission mode using barium
      fluoride windows to hold the samples was compared with transmission-reflection
      analysis with sections mounted on special infrared-reflecting slides. The two
      modes of analysis performed well in different regions of the spectrum. The mode
      of analysis (transmission vs. transmission-reflection) should be based on the
      components of greatest interest in the sample.

PMID- 16298897
TI  - A simple and rapid microwave-assisted hematoxylin and eosin staining method using
      1,1,1 trichloroethane as a dewaxing and a clearing agent.
AB  - The use and practicability of microwave-assisted staining procedures in routine
      histopathology has been well established for more than 17 years. In the study
      reported here, we aimed to examine an alternative approach that would shorten the
      duration of dewaxing and clearing steps of hematoxylin and eosin (H & E) staining
      of paraffin sections by using a microwave oven. Although xylene is one of the
      most popular dewaxing and clearing agents, its flammability restricts its use in
      a microwave oven; thus we preferred 1,1,1 trichloroethane, which is not
      flammable, as the dewaxing and clearing agent in the present study. In Group I
      and Group II (control groups), intestine was processed with xylene and 1,1,1
      trichloroethane, respectively. The sections were then stained with H & E
      according to the conventional staining protocol at room temperature and
      subdivided into two groups according to the duration of dewaxing and clearing in
      xylene. In Groups III and IV (experimental groups) similar tissues were processed
      with xylene and 1,1,1 trichloroethane, respectively; however, sections from these
      groups were divided into four subgroups to study the period required for dewaxing
      and clearing in 1,1,1 trichloroethane, then stained with H & E in the microwave
      oven at 360 W for 30 sec. Our conventional H & E staining procedure, which
      includes dewaxing, staining and clearing of sections, requires approximately 90
      min, while our method using 1,1,1 trichloroethane and microwave heating required
      only 2 min. Our alternative method for H & E staining not only reduced the
      procedure time significantly, but also yielded staining quality equal or superior
      to those stained the conventional way. Our results suggest that 1,1,1
      trichloroethane can be used effectively and safely as a dewaxing and clearing
      agent for H & E staining in a microwave oven.

PMID- 16298898
TI  - QSAR modeling and transmission electron microscopy stereology of altered
      mitochondrial ultrastructure of white blood cells in patients diagnosed as
      schizophrenic and treated with antipsychotic drugs.
AB  - Treatment of patients diagnosed as schizophrenic with antipsychotic drugs
      (neuroleptics) is known to cause occasional unexplained depletion of white blood
      cells, especially neutrophil granulocytes. It has been known for many years that
      neuroleptics can interfere with the mitochondrial respiratory chain in vitro.
      Because there has been a growing interest recently in mitochondrial targeting of
      drugs, and since a quantitative structure-activity relationship (QSAR) model that
      predicts mitochondrial accumulation of neuroleptics has been published, we
      investigated the effects of neuroleptics on white blood cell mitochondria. Venous
      blood samples were collected from both patients undergoing treatment with
      neuroleptics and healthy volunteers. The samples were processed for transmission
      electron microscopy. The resulting images of white blood cells were analyzed
      using stereology to compare quantitatively mitochondrial morphology in the
      patient and control groups. We found that in patients, but not in controls, there
      was swelling of mitochondria and fragmentation of the mitochondrial cristae.
      There also were fewer mitochondria in patients than in controls, although due to
      the swelling of the organelles, the volume density of mitochondria in the two
      groups was not significantly different. Such changes are typical of a toxic
      insult. Consequently, it seems plausible that, since schizophrenia is not a
      disease considered to affect white blood cells per se, these changes probably are
      due to the medication.

PMID- 16298899
TI  - Effects of long-term fixation on histological quality of undecalcified murine
      bones embedded in methylmethacrylate.
AB  - While long-term fixation and storage of specimens is common and useful for many
      research projects, it is particularly important for space flight investigations
      where samples may not be returned to Earth for several months (International
      Space Station) or years (manned mission to Mars). We examined two critical
      challenges of space flight experimentation: the effect of long-term fixation on
      the quality of mouse bone preservation and the preservation of antigens and
      enzymes for both histochemical and immunohistochemical analyses, and how the
      animal/sample processing affects the preservation. We show that long-term
      fixation minimally affects standard histological staining, but that enzyme
      histochemistry and immunolabeling are greatly compromised. Further, we
      demonstrate that whole animal preservation is not as suitable as whole leg or
      stripped leg preservation for long-term fixation and all histological analyses.
      Overall, we recommend whole leg processing for long-term storage of bone
      specimens in fixative prior to embedding in plastic for histological examination.

PMID- 16298900
TI  - A simple method for fixation and microdissection of frozen fresh tissue sections
      for molecular cytogenetic analysis of cancers.
AB  - Microdissection has been widely used for procuring DNA from specific microscopic
      regions of formalin fixed, paraffin embedded tissue sections. We have developed a
      method for fixation and microdissection of frozen fresh biopsy tissue sections.
      Five micrometer frozen fresh tissue sections were fixed with ethanol and stored
      at room temperature. Well defined regions from hematoxylin and eosin (H & E)
      stained or unstained sections were briefly steamed and microdissected using a
      needle. The dissected tissue was digested with proteinase K and DNA was isolated.
      Whole genome amplifications were obtained by degenerate oligonucleotide primed
      polymerase chain reaction (DOP-PCR) from these samples. The reliability of this
      technique was demonstrated by comparing conventional comparative genomic
      hybridization (CGH) with DOP-PCR-CGH. The advantages of this method are that
      frozen fresh sections can be fixed easily and stored for more than 4 years, it is
      easy to microdissect and pick-up very minute regions (0.1 mm(2)), and it is
      rapid; microdissection and purification can be accomplished within 3 h. Using DNA
      from microdissected sections, DOP-PCR-CGH revealed genetic abnormalities more
      accurately than conventional CGH. Although this novel method was demonstrated
      using DOP-PCR-CGH, we believe that it will be useful for other genetic analyses
      of specific small regions and cell populations. We also observed whether storage
      time, H & E staining and crude DNA extracts affected the quality of amplified
      DNA. DNA integrity was maintained for at least 49 months in ethanol fixed
      sections that were stored at room temperature, but DNA was gradually degraded
      after one month if the ethanol fixed sections had been H & E stained and stored.
      When crude DNA extracts from H & E stained sections were used, the size of the
      DOP-PCR product was reduced. Our study suggests that ethanol fixed tissue
      sections may be stored at room temperature for at least 4 years without DNA
      degradation, the H & E stains may not affect the quality of amplified DNA, but H
      & E or other components in the staining process may reduce the size of DOP-PCR
      product, which is critical for the quality of CGH hybridization.

PMID- 16298901
TI  - Immunolocalization of MMP-19 in the human intervertebral disc: implications for
      disc aging and degeneration.
AB  - Matrix metalloproteinases (MMPs) degrade components of the extracellular matrix
      of the disc, but the presence of MMP-19 has not been explored. In other tissues,
      MMP-19 is known to act in proteolysis of the insulin-like growth factor (IGF)
      binding protein-3, thereby exposing this protein to make it available to
      influence cell behavior. MMP-19 also has been shown to inhibit capillary-like
      formation and thus play a role in the avascular nature of the disc. Using
      immunohistochemistry, normal discs from six subjects aged newborn through 10
      years and 20 disc specimens from control donors or surgical patients aged 15-76
      (mean age 40.2 years) were examined for immunolocalization of MMP-19; six
      Thompson grade I discs, five Thompson grade II, eight Thompson grade III, five
      Thompson grade IV, and one Thompson grade V discs were analyzed. The results
      indicate that in discs from young subjects, MMP-19 was uniformly localized in the
      outer annulus. In discs from adult donors and surgical patients, outer and inner
      annulus cells only occasionally showed MMP-19 localization. The greatest
      expression of MMP-19 was observed in young discs, and little expression was seen
      in older or degenerating discs. Because MMP-19 has been shown to regulate IGF
      mediated proliferation in other tissues, its decline in the aging/degenerating
      disc may contribute to the age-related decrease in disc cell numbers.

PMID- 16298902
TI  - Ghrelin immunohistochemistry of gastric adenocarcinoma and mucoepidermoid
      carcinoma of salivary gland.
AB  - Ghrelin (G-HH) synthesized in several tissues including salivary and stomach
      glands stimulates appetite in humans by modulating neuropeptide Y neurons in the
      hypothalamic arcuate nucleus. Loss of appetite is one of the most important
      symptoms of stomach cancer. We conducted a study using immunohistochemistry to
      determine whether salivary glands and stomach cancer tissues produce ghrelin. We
      determined that negative ghrelin immunohistochemistry discriminates tumors from
      normal tissues and may therefore further our understanding of the clinically
      important problem of reduced food intake and anorexia in cancer patients.
      Radioimmunoassay analyses confirmed that cancer cells do not produce a G-HH
      peptide, whereas normal cells yield this peptide.

PMID- 16298903
TI  - Techniques for microscopic detection of asbestos bodies in lung tissue.

PMID- 16298906
TI  - Cardiovascular imaging to quantify the evolution of cardiac diseases in clinical
      development.
AB  - Cardiovascular diseases are the leading causes of mortality in western countries,
      leading to the development of a large set of preventive and curative treatments.
      Medical imaging is the gold standard to evaluate both cardiac perfusion and
      cardiac function and can be used even before the advent of hard events to
      accurately assess treatment effects. This study reviews the different image
      modalities that can be used to evaluate the evolution of cardiac diseases,
      especially coronary artery diseases. It also reviews different techniques heavily
      relying upon image co-registration techniques and population model designs that
      enable accurate quantitative evaluation of cardiac perfusion and cardiac function
      through time. It will draw the pros and cons of the different imaging modalities
      in actual clinical trials: Gated or tagged MRI, MRI for perfusion, PET, SPECT,
      Gated SPECT, MUGA, Ultrasound. This study also details the latest advances in
      quantification of cardiac SPECT, which has wide use in clinical trials today.

PMID- 16298907
TI  - F2-isoprostanes as markers of oxidative stress in vivo: an overview.
AB  - The isoprostanes are a unique series of prostaglandin-like compounds formed in
      vivo via a non-enzymatic mechanism involving the free radical-initiated
      peroxidation of arachidonic acid. This article summarizes selected aspects
      regarding current knowledge of these compounds and their value as markers of
      oxidative injury. Novel aspects related to the biochemistry of isoprostane
      formation are discussed and methods by which these compounds can be analysed and
      quantified are summarized. A considerable portion of this article examines the
      utility of F(2)-isoprostanes as markers of oxidant injury in vivo. Numerous
      studies carried out over the past decade have shown that these compounds are
      extremely accurate measures of lipid peroxidation and have illuminated the role
      of oxidant injury in a number of human diseases including atherosclerosis,
      Alzheimer's disease and pulmonary disorders.

PMID- 16298908
TI  - Isoprostanes and other markers of peroxidation in atherosclerosis.
AB  - Several lines of evidence suggest that reactive oxygen species play a role in the
      development of vasculopathies, including those that define atherosclerosis,
      hypertension and restenosis after angioplasty. Confused picture emerging from
      prospective clinical trials of anti-oxidants may reflect inadequacy of
      traditional indices of lipid peroxidation in the recruitment of appropriate
      patients and in guiding the selection of the appropriate dose of anti-oxidant to
      be tested. Ex vivo indices of oxidant stress could have questionable veracity in
      assessing the actual rate of lipid peroxidation in vivo. The measurement of F(2)
      isoprostanes (F(2)-iPs), formed non-enzimatically through free radical catalysed
      attack on esterified arachidonate, provides a reliable tool for identifying
      populations with enhanced rates of lipid peroxidation. Enhanced formation of F(2)
      iPs, together with increased in vivo platelet activation, has been reported in
      association with several cardiovascular risk factors. Thus, it has been suggested
      that F(2)-iPs may transduce oxidant stress-dependent platelet activation.
      Measurements of 8-iso-PGF(2alpha), an abundant F(2)-iP formed in vivo, in urine
      may provide sensitive biochemical end-points for the assessment of the oxidant
      status of the patient and the true efficacy of anti-oxidant therapies. The
      incorporation of such biochemical end-points in clinical trials may help to
      verify the reliability of the oxidative modification hypothesis in the
      development of atherosclerosis.

PMID- 16298909
TI  - Therapeutical effects of PPAR agonists assessed by biomarker modulation.
AB  - The metabolic syndrome is defined as the clustering of cardiovascular risk
      factors, such as glucose intolerance, hyperinsulinemia, dyslipidemia, coagulation
      disturbances and hypertension. Activators of the nuclear receptors peroxisome
      proliferator-activated receptors (PPARs) modulate several of the metabolic risk
      factors pre-disposing to atherosclerosis. Fibrates are hypolipidemic drugs
      operating through activation of PPARalpha, whereas glitazones are insulin
      sensitizers activating PPARgamma. In addition, these drugs exert pleiotropic and
      anti-inflammatory actions. This review will focus on the different effects of
      fibrates and glitazones, as measured by biomarker modulation, on the development
      of atherosclerosis and cardiovascular disease.

PMID- 16298910
TI  - Features of the metabolic syndrome and the risk of cardiovascular disease.
AB  - The metabolic syndrome is being increasingly recognized as an important risk
      factor for cardiovascular disease (CVD). While several clinical definitions have
      been proposed to identify patients with this syndrome, additional metabolic
      markers may be considered to improve one's ability to assess and predict the risk
      of CVD in this population. The objective of this short review is to provide an
      overview of the risk of CVD associated with specific features of the metabolic
      syndrome. The extent to which these markers may be used one day in clinical
      practice in primary prevention is also briefly discussed.

PMID- 16298911
TI  - Biomarkers for diagnosing and monitoring autoimmune diseases.
AB  - The goal of studies of autoimmune disease biomarkers is to identity markers that
      fluctuate with disease development and severity, but then normalize following
      successful therapy. The perfect marker could thus serve as a diagnostic tool, as
      well as a monitoring device for therapeutic drug efficacy. Current biomarker
      discovery efforts are focused on three groups of proteins reflective of the
      autoimmune disease process: (1) degradation products arising from destruction of
      affected tissues, (2) enzymes that play a role in tissue degradation and (3)
      cytokines and other proteins associated with immune activation. Potential
      biomarkers for two autoimmune diseases, rheumatoid arthritis and multiple
      sclerosis, have been described in recent publications. For rheumatoid arthritis,
      these markers (by group) include (1) aggrecan fragments, C-propeptide of type II
      collagen and cartilage oligomeric matrix protein, (2) matrix metalloprotease
      (MMP)-1, MMP-3 and MMP-1/inhibitor complexes and (3) thioredoxin, IL-16 and
      tumour necrosis factor (TNF)-alpha. For multiple sclerosis, they include (1)
      neurofilament light protein and glial fibrillary acidic protein, (2) MMP-2 and
      MMP-9 and (3) TNF-alpha and soluble vascular adhesion molecule-1. The utility of
      most of these markers is limited by their restriction to relatively inaccessible
      anatomic sites (synovial or cerebrospinal fluid). Thus, from a practical
      standpoint, the most useful autoimmune biomarkers will be those measurable in
      serum or plasma.

PMID- 16298912
TI  - Biomarkers and assessment of vaccine responses.
AB  - Vaccines for infectious diseases have in the past, and will into the future,
      relied on a variety of surrogate markers to monitor vaccine efficacy. The primary
      surrogate markers have been either the antibody titer to vaccine antigens or the
      measurement of antibody function such as anti-viral neutralizing activity. In
      recent years, the measurement of T-cell function in conjunction with or
      independent of antibody measurements have been used to assess vaccine efficacy.
      ELISPOT, flow cytometry and intra-cellular staining methods are used to determine
      the impact of vaccines on immune mediators such as interleukins, interferons, MHC
      expression and pro-inflammatory mediators. The relevant B-cell and T-cell
      surrogate markers for vaccine efficacy is dependent on the vaccine being used, so
      that no universal set of surrogate markers can be applied to all vaccines. The
      use of T-cell surrogate markers can be complicated by the lack of sensitivity to
      accurately measure intra-cellular mediators. Although typically this is not a
      problem for infectious disease vaccines, it is a major problem for cancer
      vaccines.

PMID- 16298913
TI  - Brain imaging in drug R&D.
AB  - Magnetic resonance imaging (MRI), used as a clinical diagnostic tool since the
      early 1980s, is rapidly gaining traction as an integral part of the drug
      development process. Brain imaging research spans a wide area, covering both
      structure and function, and ranging from the physics and physiology associated
      with novel acquisition techniques, to the development of sophisticated image
      processing algorithms. This paper briefly describes two methods on either end of
      this spectrum: the "pipeline" framework for the fully automated morphometric
      analysis of brain imaging data, and molecular MRI, which holds promise for the
      non-invasive detection of molecular targets of new pharmacological compounds. The
      potential use of these technologies is illustrated by examples of their
      applications in multiple sclerosis, Alzheimer's disease, and oncology.

PMID- 16298914
TI  - Can we develop biomarkers that predict response of cancer patients to
      immunotherapy?
AB  - PRIMARY OBJECTIVE: The primary objective is to delineate the potential utility of
      cancer biomarkers that correlate and predict response to immunotherapy in cancer
      patients who are refractory to conventional therapeutics. Unlike significant
      development of biomarkers that predict response to chemotherapy, very few
      biomarkers have been developed to predict the response to immunotherapy. MAIN
      OUTCOMES AND RESULTS: This article describes briefly the importance of
      characterizing and validating biomarkers for immunotherapy. A few examples have
      been provided, such as the transcription factor NF-kappaB, the transcription
      repressor Yin-Yang 1 (YY1), the pro-apoptotic gene product (Smac/DIABLO) and the
      circulating Fas and Fas ligand. These biomarkers have been determined to be of
      prognostic significance in different cancers. CONCLUSIONS: Immunotherapy is
      considered as an alternative therapy in the treatment of cancer patients who are
      refractory to chemotherapy/radiation/hormonal therapies. Cross-resistance to
      apoptosis develops between cancer cells that are resistant to conventional
      therapeutics and immunotherapy. Therefore, it is important to develop biomarkers
      that will determine patient response to immunotherapy.

PMID- 16298915
TI  - The tissue micro-array as a translational research tool for biomarker profiling
      and validation.
AB  - High-throughput molecular technologies have provided a wealth of putative
      biomarkers representing potential diagnostic, prognostic and therapeutic targets.
      Target validation commonly requires abundant and well-characterized tissue
      resources, as well as linked clinicopathologic data-sets. The tissue micro-array
      (TMA) is a validation and discovery platform of increasing popularity and
      necessity. TMAs provide a rapid means of examining in situ gene expression in a
      wide spectrum and large number of tissue samples. This paper describes the uses
      of TMAs as a translational research tool in biomarker profiling. The laboratory
      has performed numerous biomarker studies on several types of epithelial cancers.
      As an example, Epithelial Protein Cell Adhesion Molecule (EpCAM), a panepithelial
      antigen used to target tumours with immunotherapy, was examined in patients with
      renal cell carcinoma (RCC). EpCAM was an independent prognosticator for improved
      disease-specific survival in 318 clear cell RCCs examined, with a Cox
      proportional hazards multivariate hazard ratio of 0.63 (p=0.017; 95% confidence
      interval 0.43-0.92). Interestingly, despite a typically widespread epithelial
      expression, EpCAM is instead infrequently expressed in clear cell RCC, the most
      common type of renal cancer, making it a poor target for immunotherapy. In this
      capacity the TMA provided strong support for halting lengthy and costly clinical
      trials for this application.

PMID- 16298916
TI  - Biomarker discovery in urogenital cancer.
AB  - Novel approaches for the early detection of urogenital cancers are urgently
      needed. Metastatic renal cell carcinoma (RCC) has a poor prognosis and
      unpredictable course and to date there are no molecular markers that reliably
      protect RCC outcome. A novel kidney cancer marker, carbonic anhydrase IX (CA IX),
      was investigated as an independent prognostic factor for survival for patients
      with metastatic RCC. In patients with non-metastatic RCC low CAIX predicted a
      worse outcome similar to patients with metastatic disease and overall CAIX
      expression decreased with development of metastasis. CAIX reflects significant
      changes in tumour biology, which may be used to predict clinical outcome and
      identify high-risk patients for adjuvant-targeted therapies. With regard to
      prostate cancer there are a number of putative biomarkers, although there are
      limited studies providing clinical correlations in humans. Potential biomarkers
      include caveolin-1, p-Akt, p27, the met oncogene, Ki67 (MIB-1), 8q24 over
      expression, polycomb protein EZH2, plasma TGF-B1 and IL-6 among others. The
      laboratory has concentrated on the Prostate Stem Cell Antigen (PSCA) which is
      increased in patients with more aggressive features, that is higher Gleason grade
      and higher stage. Highest expression is seen in metastatic lesions to bone and
      staining for PSCA may predict for disease progression or recurrence. Also
      promising is the finding reported by the group that expression of p27 in radical
      prostatectomy specimens correlates with biochemical recurrence. Loss of p27
      (defined as absent expression in more than 70% of the specimen) is an independent
      predictor of recurrence among all patients and among the sub-set with organ
      confined and extra-capsular disease. The data also shows that p27 can predict
      outcome among patients with positive surgical resection margins. As with other
      biomarkers, major questions still to be addressed is the requirement for
      universal application with uniform scoring and the need for prospective studies
      in randomized clinical trials.

PMID- 16298917
TI  - Image-guided neurosurgery system integrating AR-based navigation and open-MRI
      monitoring.
AB  - As endoscopic surgery has become a popular form of minimally invasive surgery, it
      increasingly requires useful imaging tools to help the surgeons perform safe and
      secure operations. Our navigation system provides surgeons with visual
      information by overlaying 3D wire frame models of tumor onto live images, as well
      as by displaying relative the positions of surgical tools and the target tumor.
      Such 3D wire frame models are generated from pre-operative CT/MR images with the
      help of a 3D surgical simulation software. Another important function of our
      system is real-time volume rendering of intra-operative MR images for the target
      tumor. This function allows surgeons to carefully observe the vicinity of the
      tumor regions to be removed, by rendering the sectional views with respect to the
      surgical tool position, so that surgical performance can be easily monitored
      during the operation. We tested this navigation system in more than 10 clinical
      operations and verified the effectiveness of the navigation and surgical
      performance.

PMID- 16298918
TI  - Implementation, accuracy evaluation, and preliminary clinical trial of a CT-free
      navigation system for high tibial opening wedge osteotomy.
AB  - OBJECTIVE: The objectives of this study are to design and evaluate a CT-free
      intra-operative planning and navigation system for high tibial opening wedge
      osteotomy. This is a widely accepted treatment for medial compartment
      osteoarthritis and other lower extremity deformities, particularly in young and
      active patients for whom total knee replacement is not advised. However, it is a
      technically demanding procedure. Conventional preoperative planning and surgical
      techniques have so far been inaccurate, and often resulting in postoperative
      malalignment representing either under- or over-correction, which is the main
      reason for poor long-term results. In addition, conventional techniques have the
      potential to damage the lateral hinge cortex and tibial neurovascular structures,
      which may cause fixation failure, loss of correction, or peroneal nerve
      paralysis. All these common problems can be addressed by the use of a surgical
      navigation system. MATERIALS AND METHODS: Surgical instruments are tracked
      optically with the SurgiGATE((R)) navigation system (PRAXIM MediVision, La
      Tronche, France). Following exposure, dynamical reference bases are attached to
      the femur, tibia, and proximal fragment of the tibia. A patient-specific
      coordinate system is then established, on the basis of registered anatomical
      landmarks. After intra-operative deformity measurement and correction planning,
      the osteotomy is performed under navigational guidance. The deformities are
      corrected by realigning the mechanical axis of the affected limb from the
      diseased medial compartment to the healthy lateral side. The wedge size, joint
      line orientation, and tibial plateau slope are monitored during correction.
      Besides correcting uni-planar varus deformities, the system provides the
      functionality to correct complex multi-planar deformities with a single cut.
      Furthermore, with on-the-fly visualization of surgical instruments on multiple
      fluoroscopic images, penetration of the hinge cortex and damage to the
      neurovascular structures due to an inappropriate osteotomy can be avoided.
      RESULTS: The laboratory evaluation with a plastic bone model (Synbone AG, Davos,
      Switzerland) shows that the error of deformity correction is <1.7 degrees (95%
      confidence interval) in the frontal plane and <2.3 degrees (95% confidence
      interval) in the sagittal plane. The preliminary clinical trial confirms these
      results. CONCLUSION: A novel CT-free navigation system for high tibial osteotomy
      has been developed and evaluated, which holds the promise of improved accuracy,
      reliability, and safety of this procedure.

PMID- 16298919
TI  - How does soft tissue distribution affect anteversion accuracy of the palpation
      procedure in image-free acetabular cup navigation? An ultrasonographic
      assessment.
AB  - Navigation of the acetabular cup in total hip replacement (THR) is used to
      improve the reproducibility of acetabular component positioning. When the
      palpation of anatomic landmarks, which is necessary to determine the pelvic
      coordinate system, is performed epicutaneously, the question as to how uneven
      soft tissue distribution can influence navigation accuracy arises. To obtain
      data, the questionable soft tissue thickness was measured in 72 patients
      scheduled for THR. In addition, distances between the landmarks were recorded. On
      the basis of this information, we were able to calculate the expected
      misinterpretation of the anteversion given by a navigation system for each
      patient. The calculations suggest that a navigation system would have
      underestimated the anteversion on average by 2.8 degrees +/- 1.8 degrees. The
      median of anteversion misinterpretation was 2.4 degrees and its 95% confidence
      interval was calculated to be 2.2 degrees -3.0 degrees. No correlation with
      substantial significance between anteversion misinterpretation and the patients'
      biometrical data could be found. According to the current knowledge, acetabular
      cups in THR should be positioned within a range of 30 degrees -50 degrees of
      inclination and 10 degrees -30 degrees of anteversion. In comparison with these
      permitted +/- 10 degrees windows, the amount of misinterpretation that was found
      due to uneven soft tissue distribution seems to be acceptable.

PMID- 16298920
TI  - The impact of latency on surgical precision and task completion during robotic
      assisted remote telepresence surgery.
AB  - OBJECTIVE: It has been suggested that robotic-assisted remote telepresence
      surgery with a signal transmission latency of greater than 300 ms may not be
      possible. METHODS: We evaluated the impact of four different latencies of up to
      500 ms on task completion and error rate in five surgeons after completion of
      three different surgical tasks. RESULTS: The surgeons were able to complete all
      tasks with a latency of 500 ms. However, higher latency was associated with
      higher error rates and task completion time (TCT). There were significant
      variations between surgeons and different tasks. CONCLUSION: Surgeons are able to
      complete tasks with a signal transmission latency of up to 500 ms. The clinical
      impact of slower TCT and increased error rates encountered at higher latency
      needs to be established.

PMID- 16298921
TI  - Today's state of the art in surgical robotics*.
AB  - OBJECTIVE: This paper describes the current level of development of robots for
      surgery. MATERIAL AND METHODS: This paper is based on a literature search in
      Pubmed, IEEExplore, CiteSeer and the abstract volumes of the MICCAI 2002, 2003
      and 2004, CARS 2003 and 2004, CAOS 2003 and 2004, CURAC 2003 and 2004 and MRNV
      2004 meetings. RESULTS: Divided into different disciplines (imaging, abdominal
      and thoracic surgery, ENT, OMS, neurosurgery, orthopaedic surgery, radiosurgery,
      trauma surgery, urology), 159 robot systems are introduced. Their functionality,
      deployment, origin and mechanical set-up are described. Additional contacts and
      internet links are listed. CONCLUSIONS: The systems perform diverse tasks such as
      milling cavities in bone, harvesting skin, screwing pedicles or irradiating
      tumors. From a technical perspective the strong specialization of the systems
      stands out. Most of the systems are being developed in Germany, the United
      States, Japan or France.

PMID- 16298922
TI  - A cost-effectiveness analysis of a health education programme for elderly persons
      with age-related macular degeneration: a longitudinal study.
AB  - PURPOSE: To analyse the cost-effectiveness of the activity-based Health Education
      Programme 'Discovering New Ways' versus a standard Individual Programme. METHOD:
      Two-hundred and twenty-nine persons were randomized to either the Health
      Education Programme or an Individual Programme. The present study is based on 131
      persons who participated in the 28-month follow-up. Costs for the low vision
      clinic were documented prospectively along with external costs. A cost
      effectiveness analysis was done using cases with an improved level of perceived
      security in daily activities as the effectiveness measure. RESULTS: The Health
      Education Programme led to significantly more cases with an improved level of
      perceived security (45 vs. 10%, CI 95%: 21-49, p value < 0.001) and the total
      social cost per treatment was lower (28,004 vs. 36,341 SEK). Taken separately the
      low vision clinic costs were slightly higher due to a higher prescription of
      assistive devices, but external costs were lower for the Health Education
      Programme compared to the Individual Programme, though neither of these
      differences was statistically significant. CONCLUSION: The results suggest that
      replacing the standard Individual Programme with the Health Education Programme
      'Discovering New Ways' is cost-effective as more persons experience increased
      security to a lesser total cost.

PMID- 16298923
TI  - Upper limb recovery after stroke: the stroke survivors' perspective.
AB  - PURPOSE: This study investigated stroke survivors' perspective of upper limb
      recovery after stroke. The aim was to determine factors other than medical
      diagnosis and co-morbidities that contribute to recovery. The objectives were to
      explore how stroke survivors define recovery, identify factors they believe
      influence recovery and determine strategies used to maximize upper limb recovery.
      METHOD: A qualitative study consisting of three focus groups and two in-depth
      interviews was conducted with stroke survivors (n = 19) and spouses (n = 9) in
      metropolitan, regional and rural Queensland, Australia. Data were analysed using
      principles of grounded theory. RESULTS: Stroke survivors maximize upper limb
      recovery by 'keeping the door open' a process of continuing to hope for and work
      towards improvement amidst adjusting to life with stroke. They achieve this by
      'hanging in there', 'drawing on support from others', 'getting going and keeping
      going with exercise', and 'finding out how to keep moving ahead'. CONCLUSIONS:
      This study provides valuable insight into the personal experience of upper limb
      recovery after stroke. It highlights the need to develop training strategies that
      match the needs and aspirations of stroke survivors and that place no time limits
      on recovery. It reinforces the benefits of stroke support groups and advocates
      their incorporation into stroke recovery services. These findings can be used to
      guide both the development and evaluation of stroke survivor centred upper limb
      training programmes.

PMID- 16298924
TI  - Development and factor analysis of an index of post-polio sequelae.
AB  - PURPOSE: This present study describes the development, factor structure and
      initial validation of the Index of Post-Polio Sequelae (IPPS). METHOD: The IPPS
      was tested on a sample of 849 community-dwelling polio survivors between the ages
      of 40 and 93 years old who participated in a large, national study of menopause
      and aging in late polio. Items from the IPPS were submitted to a factor analysis
      using principal components extraction and rotated to oblique simple structure
      using promax rotation. Convergent validity was assessed using bivariate
      correlation. RESULTS: Three factors were extracted that accounted for
      approximately 53% of the variance in the original IPPS items. Factor 1 (Pain) was
      loaded most heavily by two items referring to muscle and joint pain. Factor 2
      (Atrophy) was loaded by items referring to muscle atrophy, involved muscle
      weakness, and fatigue. Factor 3 (Bulbar) was comprised of two items referring to
      breathing and swallowing problems. Bivariate correlations between health and
      psychosocial variables and each of the factors all were significant and in
      expected directions. CONCLUSIONS: This first validation of a standardized scale
      to assess the severity of post-polio sequelae in polio survivors suggests a
      psychometrically sound instrument whose factor structure represents commonly
      reported problems in the extant post-polio literature.

PMID- 16298925
TI  - Interactive virtual environment training for safe street crossing of right
      hemisphere stroke patients with unilateral spatial neglect.
AB  - PURPOSE: The goal of this study was to determine whether non immersive
      interactive virtual environments are an effective medium for training individuals
      who suffer from Unilateral Spatial Neglect (USN) as a result of a right
      hemisphere stroke, and to compare it to a standard computer visual scanning
      training. METHOD: Participants included 19 patients with right hemisphere stroke
      in two groups, 11 in an experimental group were given computer desktop-based
      Virtual Reality (VR) street crossing training and 8 in a control group who were
      given computer based visual scanning tasks, both for a total of twelve sessions,
      9 hours total, over four weeks. Measures included: 1. Standard USN assessments,
      paper and pencil and ADL checklist; 2. Test on the VR street program; and 3.
      Actual street crossing videotaped. Testing was performed pre and post
      intervention. RESULTS: The VR group achieved on the USN measures results that
      equaled those achieved by the control group treated with conventional visual
      scanning tasks. They improved more on the VR test and they did better on some
      measures of the real street crossing. CONCLUSIONS: Despite several limitations in
      this study the present results support the effectiveness of the VR street program
      in the treatment of participants with USN, and further development of the
      program.

PMID- 16298926
TI  - Responsiveness of evaluative measures for children with cerebral palsy: the Gross
      Motor Function Measure and the Pediatric Evaluation of Disability Inventory.
AB  - PURPOSE: The aim of this study is to describe responsiveness of the Gross Motor
      Function Measure (GMFM) and the Pediatric Evaluation of Disability Inventory
      (PEDI) in a group of children with cerebral palsy (CP). METHOD: The subjects were
      55 children with cerebral palsy aged 2 to 7 years (mean 4.6 years). We described
      the responsiveness of the GMFM and PEDI for all children (n = 55), for children
      younger than 4 years of age (n = 22) and those older or equal to 4 years (n =
      33). Two frames of references for determining responsiveness were used: change
      over time and external criterion. Responsiveness was calculated with help of the
      Effect Size (ES), Standardised Response Mean (SRM) and Spearman rank order
      correlations of change on both the PEDI and GMFM, with change in motor
      functioning according to the parents as external criterion. RESULTS: The PEDI has
      ES and SRM values higher than 0.8. The GMFM has ES and SRM values higher than
      0.5. For all dimensions of the PEDI and for almost all dimensions of the GMFM,
      the ESs and SRMs of the younger group are higher than those of the older group.
      The ES and the SRM of the GMFM increase with the complexity of the task. When
      looking at the correlations of the PEDI and GMFM change scores with the opinion
      of parents, the results are less unequivocal. CONCLUSIONS: Both the GMFM and the
      PEDI are responsive for change in motor ability over time in children with CP,
      the most in children younger than 4 years of age.

PMID- 16298927
TI  - Deep vein thrombosis and pulmonary embolism in an ambulatory chronic stroke
      patient.
AB  - PURPOSE: Deep vein thrombosis (DVT) is a well-known complication of stroke and
      frequently develops in acute stroke patients. Immobility in stroke patients
      increases the risk of DVT and pulmonary embolism (PE). The incidence of DVT in
      non-ambulatory stroke patients is more frequent than the incidence in ambulatory
      stroke patients. We report a case of DVT and PE in an ambulatory chronic stroke
      patient. METHOD: Initial physical examination showed heat and swelling of
      hemiplegic leg. The patient was only able to ambulate with the assist of a
      monocane and a plastic leaf spring orthosis due to ankle dorsiflexor weakness.
      The patient was treated with anticoagulation and inferior vena cava filter
      placement. RESULTS: After long-term anticoagulation, follow-up studies revealed
      satisfactory resolution of DVT and PE. CONCLUSIONS: We present a case of DVT and
      PE which developed during the chronic stage of stroke, 2 years from the onset of
      stroke, and review the cause of DVT.

PMID- 16298928
TI  - Has the Disability Discrimination Act closed the employment gap?
AB  - STUDY OBJECTIVE: To investigate whether the disparity in employment rates between
      people with a limiting long-term illness or disability and those without has
      decreased since the implementation of the Disability Discrimination Act in the
      UK. DESIGN: National cross-sectional data on employment rates for people with and
      without a limiting long-term illness or disability were obtained from the General
      Household Survey for a twelve-year period (1990-2002; 10 surveys). Representative
      population samples were analysed. The sample size for the GHS over the study
      period ranged from 19,193 to 24,657 and the average response rate ranged from 72%
      to 82%. MAIN OUTCOME MEASURE: The relative employment rates of men and women of
      working age (18-60/65 years). Compares people with a limiting long-term illness
      or disability ('disabled') with people with no limiting long-term illness or
      disability ('not disabled'). RESULTS: Age standardised employment rates remained
      relatively stable from 1990 to 2001 for people defined as 'not disabled'.
      However, the employment rates of people defined as 'disabled' have decreased
      since 1990, and were at their lowest following the implementation of the
      employment aspects of the DDA in 1996 (1998-2002). In addition the gap between
      the employment rates of people defined as 'disabled' and 'not disabled' was most
      marked after the DDA between 1998-2002 (p < 0.05). CONCLUSIONS: This appraisal of
      routine population data pre- and post- the Disability Discrimination Act
      indicates that the legislation may not have been effective in closing the
      employment gap that exists in the UK between people with a limiting long-term
      illness or disability and those without.

PMID- 16298930
TI  - Concerns and expectations about returning to work with low back pain: identifying
      themes from focus groups and semi-structured interviews.
AB  - PURPOSE: Studies of occupational low back pain (OLBP) have shown that return to
      work after injury is influenced by workers' concerns and expectations; however,
      these theoretical constructs have not been explored. The specific aim of this
      study was to identify themes related to self-efficacy and outcome expectancy for
      returning to work using qualitative research methods. METHOD: Twenty-eight
      individuals who recently returned to work (< 6 months) after an onset of OLBP
      responded to a newspaper advertisement and participated in focus groups. In a
      second phase of the study, patients with OLBP and an impending return to work (n
      = 23) were referred by their physiotherapists and interviewed to provide more
      immediate accounts of their concerns and experiences. Notes and recordings from
      both sources were searched for utterances describing beliefs about self-efficacy
      or outcome expectancy for returning to work. RESULTS: Two primary self-efficacy
      constructs emerged: self-efficacy for resuming physical activity and self
      efficacy for resuming work. Self-efficacy for resuming physical activity included
      8 sub-domains: lift, carry, sit, stand, push/pull, bend, climb, and reach. Self
      efficacy for resuming work included 3 sub-domains: pain control, obtaining help,
      and meeting job demands. Outcome expectancy included four sub-domains:
      financial/job security, re-injury, workplace support, and self-image.
      CONCLUSIONS: Hesitation to return to work after OLBP involves not only concerns
      about pain and re-injury, but also the perceived ability to perform physical
      tasks, meet role expectations, obtain workplace support, and maintain job
      security.

PMID- 16298931
TI  - The meaning of spirituality for individuals with disabilities.
AB  - PURPOSE: To examine the experiences of people with disabilities regarding their
      spirituality and its meaning for them. This study asked: What are the differences
      in the meaning of spirituality in the lives of individuals with childhood onset
      disabilities when compared to those with adult onset disabilities? METHOD: This
      qualitative study involved semi-structured individual interviews of 12 adults,
      six with childhood onset and six with adult onset disabilities. Member checking
      of both transcribed data and open coding was done to ensure trustworthiness. Data
      was analyzed using open, axial, and selective coding. RESULTS: Findings suggested
      that the two groups held different perceptions about the meaning of spirituality.
      For childhood onset participants, two categories of 'connecting and expressing
      for purpose and meaning in life', and 'disability as a vehicle to discover god's
      purpose' were generated. For adult onset participants, two categories of
      'connecting and expressing through feelings and actions', and 'disability as a
      catalyst for spiritual awakening' were derived from the data. CONCLUSIONS:
      Individuals with childhood and adult onset disabilities perceive and experience
      spirituality differently. Therefore, different approaches to using spirituality
      in practice need to be employed for the two groups. Suggestions are provided for
      incorporating spirituality into occupational therapy practice.

PMID- 16298932
TI  - Employment participation following spinal cord injury: relation to selected
      participant demographic, injury and psychological characteristics.
AB  - PURPOSE: To determine the relationship between selected demographic, injury and
      psychological characteristics and the extent of employment undertaken following
      spinal cord injury (SCI). METHOD: Data were collected from 289 persons with SCI
      who found employment post-injury. A survey was administered to patients of a
      specialist spinal cord injury unit located in South-Eastern Australia. A variety
      of demographic, injury and psychological variables were assessed for their
      relationship to the extent of employment undertaken following SCI. Extent of
      employment, was defined as time spent employed as a proportion of the time
      available for employment, and is hereafter referred to as "workrate." RESULTS: On
      average, participants reported having been employed for almost two-thirds of
      their available time. Study variables explained 22% (18% adjusted) of the
      variance in post-injury workrate. Individually, demographic and psychological
      variables, but not injury variables, were found to relate to the outcome measure.
      CONCLUSION: Using a novel measure of employment outcome, this study yielded
      findings consistent with other research using alternate employment measures.
      Results suggest that demographic and psychological variables are more related to
      this measure of employment participation than are injury variables. The addition
      of environmental variables may allow for the explanation of more variance in
      outcome.

PMID- 16298933
TI  - Patients' experiences with self-referral to in-patient rehabilitation: a
      qualitative interview study.
AB  - PURPOSE: To describe objectives, experiences and satisfaction among subjects
      referring themselves to in-patient rehabilitation. METHOD: Persons suffering from
      stroke or multiple sclerosis were invited to refer themselves to a specialised
      rehabilitation department. Ten patients referred themselves within the study
      period, of whom two were excluded. The remaining eight underwent qualitative semi
      structured in-depth interviews, focusing on the decision of self-referral, the
      personal goals for the rehabilitation, and the satisfaction with the stay. The
      interviews were tape-recorded and subjected to content analysis. As an underlying
      theoretical framework, we applied Antonovsky's Sense of Coherence model. RESULTS:
      Half of the patients had not written the application themselves and did not know
      which grounds had been put forward in the application. Nevertheless, all the
      patients were able to formulate their personal goals for the rehabilitation stay.
      These were distributed in three main categories: those who recently had got a
      progressive disability wanted education and improved knowledge on their disease;
      those who had had an acute, traumatic change of health status wanted training in
      order to improve muscular strength or everyday skills; and those who had been
      disabled for several years wanted inspiration for further life. CONCLUSIONS:
      Patients may put forward other reasons to apply for rehabilitation than health
      personnel. Does the Sense of Coherence Model seems applicable to describe these
      reasons.

PMID- 16298934
TI  - Economic assessment of pressure sore prevention using a computerized mattress
      system in patients with spinal cord injury.
AB  - PURPOSE: To assess the economic profitability of a new computerized mattress
      system in patients with spinal cord injuries (SCI) by comparison with two other
      alternatives, as an example of the use of a quantitative approach for decision
      making in choosing between alternatives for sore prevention. METHOD: The cost of
      achieving one day without signs of impending pressure sore was compared between
      the alternative options using cost minimization analysis. Savings in nursing
      costs for the three options were calculated for cost-benefit analysis. RESULTS: A
      foam mattress system is significantly cheaper than the other examined
      alternatives, and if the nursing manpower cost is constant and the nursing staff
      is capable of performing sufficient repositioning, this system would achieve the
      desired medical outcome at a minimal cost. However, if the nursing staff cannot
      perform sufficient repositioning, or if the use of nursing manpower can be
      adjusted to the actual need, then it is the computerized mattress system that
      achieves the desired outcome at the minimal cost. In this case, less than 20 New
      Israeli Shekels (NIS) per day spent on the equipment save NIS 45 per day in labor
      costs. CONCLUSIONS: The economic evaluation indicates that the computerized
      mattress system is advisable for patients with SCI who require assistance for
      repositioning, but its profitability depends on the employment terms of the
      nursing manpower. In addition, other possible alternative pressure management
      systems should be examined, and additional research may be needed to determine
      the optimal combination of such systems for a spinal cord rehabilitation
      department.

PMID- 16298935
TI  - Predictors of assistive technology use: the importance of personal and
      psychosocial factors.
AB  - OBJECTIVE: To validate an assistive technology (AT) baseline and outcomes measure
      and to quantify the measure's value in determining the best match of consumer and
      AT considering consumer ratings of their subjective quality of life, mood,
      support from others, motivation for AT use, program/therapist reliance, and self
      determination/self-esteem. DESIGN: Prospective multi-cohort study. SETTING:
      Vocational rehabilitation offices and community. PARTICIPANTS: Over 150
      vocational rehabilitation counselors in 25 U.S. states with one consumer each
      receiving new AT. INTERVENTIONS: Counselor training in the Matching Person and
      Technology (MPT) Model and consumer completion of the MPT measure, Assistive
      Technology Device Predisposition Assessment (ATD PA). MAIN OUTCOME MEASURES:
      Total and subscale scores on the ATD PA as well as counselor-completed
      questionnaires. RESULTS: ATD PA items differentiated consumer predispositions to
      AT use as well as AT and user match. There were no significant differences due to
      gender, physical locality, or age within this sample of working-age adult
      consumers. Vocational rehabilitation counselors exposed to training in the MPT
      Model achieved enhanced AT service delivery outcomes. CONCLUSIONS: The ATD PA is
      a valid measure of predisposition to use an AT and the subsequent match of AT and
      user. Rehabilitation practitioners who use the ATD PA will achieve evidence-based
      practice and can expect to see enhanced AT service delivery outcomes.

PMID- 16298937
TI  - Reduction of oral mucositis by palifermin (rHuKGF): dose-effect of rHuKGF.
AB  - PURPOSE: The aim of the present study was to determine the dose effect of
      palifermin (recombinant human keratinocyte growth factor, rHuKGF) for reduction
      of the response of oral mucosa to fractionated radiotherapy in a mouse model.
      MATERIAL AND METHODS: Ulceration (confluent mucositis) of mouse tongue epithelium
      was analysed as the clinically relevant endpoint. Palifermin at doses from 1 - 30
      mg/kg was administered before the onset (day -3), at the end of the first (day
      +4) or the second week of irradiation (day +11) with 5 x 3 Gy/week. Each protocol
      was terminated by graded radiation test (top-up) doses. In a further experiment,
      optimally effective doses were given on days -3 and +4, or -3, +4 and +11.
      RESULTS: Single dose irradiation of mouse mucosa yielded an ED50 (dose inducing
      ulcer in 50% of the mice) of 10.7 +/- 1.0 Gy. With fractionated irradiation for 1
      week an ED50 for test irradiation (day +7) of 5.1 +/- 1.9 Gy was observed. After
      2 weeks (day +14), the ED50 was 7.3 +/- 1.9 Gy. Palifermin significantly
      increased the ED50 values in all protocols tested. Maximally effective doses for
      single injections were 15.0 mg/kg (day -3, +11) or 22.5 mg/kg (day +4), which
      yielded ED50 values of 12.1 +/- 1.3 Gy, 13.7 +/- 1.5 Gy and 14.4 +/- 1.3 Gy,
      respectively. Higher palifermin doses did not further increase the ED50. Repeated
      injections on days -3 and +4 did not increase the ED50 beyond the value obtained
      with injections on day +4 alone. An additional injection on day +11 increased the
      ED50 further to 15.1 +/- 0.1 Gy. CONCLUSIONS: A significant palifermin dose
      effect was seen at doses below 15 mg/kg. However, a significant increase in oral
      mucosal radiation tolerance by palifermin over untreated control tissue was
      observed already with low doses of 1 mg/kg. This indicates that in clinical
      studies with palifermin, the dose of the growth factor may be of minor relevance
      over a wide dose range.

PMID- 16298936
TI  - Road traffic accidents and disability: a cross-section study from Turkey.
AB  - PURPOSE: To investigate socio-demographic features, lesions which caused
      disabilities and the rate of disabilities caused by particular lesions and thus
      to reveal how disabilities are evaluated and general characteristics of
      disabilities due to road traffic accidents in Turkey. METHOD: In this study we
      retrospectively reviewed 563 victims of road traffic accidents evaluated by the
      Department of Forensic Medicine, Ankara University, between 1 July 1993 and 31
      December 2002 to determine whether they had disabilities and to estimate the rate
      of disabilities. We collected data about age, gender, trials outcomes, affected
      body parts, surgical interventions, lesions taken into account in estimation of
      disabilities, the rate of disabilities. RESULTS: 64.7% of the cases were male and
      35.3% were female. The mean age of the cases was 33.11 (SD:16.70) years. The most
      frequently affected body part was lower extremities and 73.6% of lesions taken
      into account in estimation of the rate of disability were located in the pelvis
      and lower extremities. CONCLUSIONS: In order to prevent these injuries, the
      mechanisms of the injuries should be determined and to this aim findings obtained
      at the scene, hospital records and findings obtained at the physical examination
      of the victims should be linked. Larger studies are needed to determine
      preventive measures for elimination of the causes of accidents, prevent permanent
      disabilities, plan education programs and make recommendations about the
      preventive measures.

PMID- 16298938
TI  - Human fibroblast growth factor 20 (FGF-20; CG53135-05): a novel cytoprotectant
      with radioprotective potential.
AB  - The aim was to evaluate the radioprotective properties of recombinant human
      fibroblast growth factor 20 (FGF-20; CG53135-05) in vitro and in vivo and to
      examine its effects on known cellular pathways of radioprotection. Relative
      transcript levels of the cyclooxygenase 2 (COX2), Mn-super oxide dismutase (SOD),
      CuZn-SOD, extracellular (EC)-SOD, nuclear respiratory factor 2 (Nrf2),
      glutathione peroxidase 1 (GPX1) and intestinal trefoil factor 3 (ITF3) genes,
      which are involved in radiation response pathways, were assessed by reverse
      transcriptase-polymerase chain reaction (RT-PCR) in NIH/3T3, IEC18, CCD-18Co, CCD
      1070sk and human umbilical vein endothelial cells (HUVEC) cells exposed to FGF
      20. Activation of the radioprotective signal transduction pathways initiating
      with the serine/threonine Akt kinase and the extracellular regulated kinase (ERK)
      were analysed. Levels of intracellular hydrogen peroxide and cytosolic redox
      potential were also measured in irradiated and unirradiated cells in the presence
      or absence of FGF-20. The effects of FGF-20 on cell survival in vitro following
      ionizing radiation were evaluated using clonogenic assays. To test the potential
      activity of FGF-20 as a radioprotectant in vivo, mice were administered a single
      dose of FGF-20 (4 mg kg(-1), intraperitoneally (i.p.) 1 day before lethal total
      body irradiation and evaluated for survival. In vitro exposure to FGF-20
      increased expression of the Nrf2 transcription factor and oxygen radical
      scavenging enzymes such as MnSOD, activated signal transduction pathways (ERK and
      Akt) and resulted in increased survival of irradiated cells in vitro. FGF-20
      treatment also resulted in a concomitant reduction in intracellular levels of
      injurious reactive oxygen species (ROS) following acute ionizing irradiation.
      Finally, prophylactic administration of FGF-20 to mice before potentially lethal,
      whole-body X-irradiation led to significant increases in overall survival. FGF-20
      reduced the lethal effects of acute ionizing radiation exposure in cells by up
      regulating important signalling and free radical scavenging pathways. Survival
      sparing effects of FGF-20 prophylaxis in acutely irradiated mice presumably are
      elicited by comparable mechanisms. These results indicate that FGF-20, has
      significant radioprotective attributes with potential applications in clinical
      and non-clinical exposure settings.

PMID- 16298939
TI  - Apoptosis induced by high-LET radiations is not affected by cellular p53 gene
      status.
AB  - To learn more about the biological effects of high-linear energy transfer (LET)
      radiations, we examined radiation-induced apoptosis in response to high-LET
      radiations in cells with wild-type, mutated and null p53 gene. Three human lung
      cancer cell lines were used. These lines had identical genotypes, except for the
      p53 gene. Cells were exposed to X-rays or high-LET radiations (13 - 200 keV
      microm(-1)) using different nuclei ion beams. Cellular radiation sensitivities
      were determined with the use of colony-forming assays. Apoptosis was detected and
      quantified using Hoechst 33342 staining with fluorescence microscopy. It was
      found that (1) there was no significant difference in cellular sensitivity to
      high-LET radiation (>85 keV microm(-1)), although the sensitivity of wild-type
      p53 cells to X-rays was higher than that of mutated p53 or p53-null cells; (2) X
      ray-induced apoptosis at higher frequencies in wild-type p53 cells when compared
      with mutated p53 and p53-null cells; and (3) Fe beams (200 keV microm(-1))
      induced apoptosis in a p53-independent manner. The results indicate that high-LET
      radiations induces apoptosis in human lung cancer cells in a manner that does not
      seem to depend on the p53 gene status of the cells.

PMID- 16298940
TI  - Studies on radiation-induced apoptosis in G0 human lymphocytes.
AB  - PURPOSE: To determine the relationships between the frequencies of radiation
      induced chromosomal alterations and the extent of apoptosis in G0 human
      lymphocytes. MATERIAL AND METHODS: G0 human peripheral blood lymphocytes (HPBL)
      were X or gamma-irradiated, in the presence or absence of the repair inhibitor
      cytosine arabinoside (Ara-C). Directly after irradiation, a part of the
      lymphocytes were stimulated to grow while the rest were stimulated 48 h after
      irradiation. These lymphocyte cultures were analysed for induction of chromosomal
      aberrations. A subset of lymphocytes was kept in G0 and analysed for cell
      viability, apoptosis and p53 expression. RESULTS: The fraction of cells bearing
      dicentrics was reduced in lymphocytes stimulated to grow 48 h post irradiation as
      compared to lymphocytes stimulated immediately after irradiation. The decrease in
      the frequency of dicentrics correlated with the increase in the number of
      apoptotic cells. The operative apoptotic pathway in irradiated Go lymphocytes was
      dependent on the expression of p53. CONCLUSIONS: The radiation-induced apoptotic
      response of G0 lymphocytes is p53 dependent and increases with the time they are
      held in G0. When mitogen was added 48 h after irradiation, cells with dicentrics
      were either preferentially eliminated or did not enter mitosis. Thus the
      radiation-induced damage can be underevaluated depending on the time between
      radiation exposure and the induction of proliferation. These results may have
      relevance for biodosimetry studies or for evaluations of the efficacy of
      radiotherapy which are based on the frequencies of chromosomal aberrations.

PMID- 16298941
TI  - Sensitivity to polychromatic UV-radiation of strains of Deinococcus radiodurans
      differing in their DNA repair capacity.
AB  - PURPOSE: To characterize the ultraviolet (UV) sensitivity and establish the UV
      induced DNA damage profile of cells of four Deinococcus radiodurans strains. The
      investigated strains differ in their radiation susceptibility, leading to a
      classification into a UV-sensitive (UVS78 and 1R1A) and a UV-resistant class
      (wild type strain R1 and 262). MATERIALS AND METHODS: Deinococcus radiodurans
      cells were exposed in suspension to monochromatic 254 nm (UV-C) and polychromatic
      UV radiations; the surviving fraction was determined by assessing the ability of
      the bacteria to form colonies. The UV-induced DNA lesions were measured
      quantitatively using an accurate and highly specific assay that involves the
      combination of high performance liquid chromatography (HPLC) with tandem mass
      spectrometry detection. RESULTS: Analysis of the DNA photoproducts showed that
      the TC (6-4) photoproduct and the TT and TC cyclobutane dimers were the major
      lesions induced by UV-C and UV-(>200 nm)-radiation. The UV-sensitive class was
      approx. 10 times more susceptible to UV-C and UV-(>200 nm)-radiations than the
      resistant class. Interestingly, the survival curves of all investigated strains
      become similar with longer UV wavelengths in the UV-(>315 nm)-radiation range.
      This observation suggests that the repair mechanisms of the UV-resistant class
      are not specifically effective for damage produced by UV of the >315 nm range.
      However, the initial amount of DNA photoproducts produced upon irradiation was
      found to be the same in resistant and sensitive strains for each wavelength
      range. CONCLUSION: Compared to mammalian cells, the DNA of Deinococcus
      radiodurans cells is less susceptible to the photo-induced formation of thymine
      cyclobutane dimers as inferred from comparative analysis. The ongoing
      investigations may contribute to a better understanding of the mechanism of DNA
      photoprotection against the direct effects of UV radiation. This may be of
      interest in the present context of a possible continuous decrease in the ozone
      layer thickness.

PMID- 16298942
TI  - Full-color painting reveals an excess of radiation-induced dicentrics involving
      homologous chromosomes.
AB  - PURPOSE: To determine the ratio of homologous to heterologous dicentric
      chromosomes induced in human cells by ionizing radiation. This ratio is
      influenced by, and thus potentially informative about, underlying DNA
      damage/repair/misrepair processes and also the geometry of individual chromosome
      domains within the interphase nucleus. MATERIALS AND METHODS: 24-color mFISH
      (multiplex fluorescent in situ hybridization) was used to determine the ratio of
      1-color (homologous) to 2-color (heterologous) dicentrics produced in human
      lymphocytes or fibroblasts by gamma-rays, alpha particles, or iron ions at
      various doses. Assuming that randomness independent of homology holds, the
      expected homologue:heterologue ratio for diploid human male cells is
      approximately 0.024, as shown by deriving a formula applicable to simple
      interchanges and then extending the result, via Monte Carlo simulation, to the
      general situation where complex aberrations are also considered. RESULTS AND
      CONCLUSIONS: There was a substantial excess of homologous dicentrics, with
      probability of occurrence by chance less than 0.02 for each of the three
      radiations and only about 10(-8) for all the data combined. Overall,
      approximately 18 homologous dicentrics were expected but 47 were found, including
      11 involving chromosome 1. Observed excesses were similar for both sparsely and
      densely ionizing radiations. Geometric proximity of homologues is a possible
      explanation for the overabundance; in that case more extensive statistics should
      eventually uncover a linear energy transfer (LET) dependence. An alternative
      possibility, not ruled out by the present data, is homology-dependent misrepair.

PMID- 16298944
TI  - The importance of the "human" in the identification of postural risk factors for
      musculoskeletal disorders.

PMID- 16298943
TI  - EGF-receptor targeted liposomes with boronated acridine: growth inhibition of
      cultured glioma cells after neutron irradiation.
AB  - PURPOSE: To study survival of cultured U-343MGaCl 2:6 glioma cells after
      incubation with boron-containing liposomes targeting the epidermal growth factor
      receptor following neutron irradiation. MATERIALS AND METHODS: Epidermal growth
      factor-tagged liposomes were loaded with water-soluble boronated acridine
      developed for boron neutron capture therapy, (BNCT). Cellular uptake and
      distribution were studied. Further, cells were placed at 3 cm depth in a phantom
      and exposed to an epithermal neutron beam to study clonogenic cell survival.
      RESULTS: The cellular uptake of boron reached 90 ppm and it was determined by
      subcellular fractionation that most of the cell-associated boron was located
      outside of the nucleus. For clonogenic survival, the cells were incubated with
      epidermal growth factor receptor-targeted liposomes for 4 hours resulting in a
      cellular concentration of 55 ppm boron (11 ppm 10B). At a fluence of 3 x 10(12)
      neutrons/cm2 the cell killing effect of the boron-containing epidermal growth
      factor-liposomes was about ten times higher than for neutrons only. Furthermore,
      theoretical calculation of the survival by enriched compound (55 ppm 10B), using
      the parameters from non-enriched compound (11 ppm 10B), shows that the killing
      effect in this case would be approximately five orders of magnitude higher than
      for neutrons only. CONCLUSION: The results in this study show that epidermal
      growth factor-receptor targeted liposomes are suitable as tumor-cell delivery
      agents of boron for BNCT and support further studies to demonstrate their
      effectiveness in vivo.

PMID- 16298947
TI  - Sampling and analysis issues relating to the ACGIH notice of intended change for
      the beryllium threshold limit value.

PMID- 16298948
TI  - Use of green fluorescent protein-expressing Aspergillus fumigatus conidia to
      validate quantitative PCR analysis of air samples collected on filters.
AB  - This study used green fluorescent protein (GFP)-expressing Aspergillus fumigatus
      conidia to compare quantitative PCR (qPCR) enumeration with direct epifluorescent
      microscopic filter counts of conidia collected on filters in a test chamber. In
      separate experiments this study initially compared white versus fluorescent light
      microscopy for counting A. fumigatus conidia, then compared fluorescent
      microscopy counting of corresponding filter halves, and finally compared qPCR
      enumeration to counting by fluorescent light microscopy. The use of GFP
      expressing conidia with epifluorescent microscopy yielded significantly higher
      conidia counts (p = 0.026, n = 41, mean of 4.1 conidia per counting field) and
      40% faster counting times when compared to conventional counting using white
      light microscopy. GFP-expressing conidia were aerosolized in a test chamber and
      collected onto filters. Filters were divided in half and GFP-expressing conidia
      enumerated. There was no significant difference in the average conidia count per
      field between corresponding filter halves (p = 0.3, n = 9 filters, mean of 7.8
      conidia per counting field). Thus, one filter half could be counted optically and
      would provide a reliable estimate of filter loading of the corresponding half,
      which could then be analyzed by qPCR. Filters (n = 38) loaded with GFP conidia in
      the aerosol chamber were divided in half and analyzed by either fluorescent
      microscopy or qPCR. The estimated filter loadings ranged from 15-30,000 conidia
      per filter. There was a linear relationship with a nearly 1:1 ratio between qPCR
      and direct microscopic estimates of filter loading (y = 1.06x + 404; R(2) = 0.91)
      showing that the outlined qPCR analysis method is in agreement with an external
      reference method and is reliable for enumerating A. fumigatus conidia collected
      on filters. The comparative data derived using GFP-expressing conidia confirmed
      that qPCR provides sensitive and accurate quantification of DNA from airborne
      conidia collected on filters.

PMID- 16298949
TI  - The effect of subject characteristics and respirator features on respirator fit.
AB  - A recent study was conducted to compare five fit test methods for screening out
      poor-fitting N95 filtering-facepiece respirators. Eighteen models of NIOSH
      certified, N95 filtering-facepiece respirators were used to assess the fit test
      methods by using a simulated workplace protection factor (SWPF) test. The purpose
      of this companion study was to investigate the effect of subject characteristics
      (gender and face dimensions) and respirator features on respirator fit. The
      respirator features studied were design style (folding and cup style) and number
      of sizes available (one size fits all, two sizes, and three sizes). Thirty-three
      subjects participated in this study. Each was measured for 12 face dimensions
      using traditional calipers and tape. From this group, 25 subjects with face size
      categories 1 to 10 tested each respirator. The SWPF test protocol entailed using
      the PortaCount Plus to determine a SWPF based on total penetration (face-seal
      leakage plus filter penetration) while the subject performed six simulated
      workplace movements. Six tests were conducted for each subject/respirator model
      combination with redonning between tests. The respirator design style (folding
      style and cup style) did not have a significant effect on respirator fit in this
      study. The number of respirator sizes available for a model had significant
      impact on respirator fit on the panel for cup-style respirators with one and two
      sizes available. There was no significant difference in the geometric mean fit
      factor between male and female subjects for 16 of the 18 respirator models.
      Subsets of one to six face dimensions were found to be significantly correlated
      with SWPFs (p < 0.05) in 16 of the 33 respirator model/respirator size
      combinations. Bigonial breadth, face width, face length, and nose protrusion
      appeared the most in subsets (five or six) of face dimensions and their multiple
      linear regression coefficients were significantly different from zero (p < 0.05).
      Lip length was found in only one subset. The use of face length and lip length as
      the criteria to define the current half-facepiece respirator fit test panel may
      need to be reconsidered when revising the panel. Based on the findings from this
      and previous studies, face length and face width are recommended measurements
      that should be used for defining the panel for half-facepiece respirators.

PMID- 16298950
TI  - Predicting historical dust and wood dust exposure in sawmills: model development
      and validation.
AB  - Nonspecific dust measurements are used as a surrogate for wood dust exposure in
      sawmills. However, the wood dust component of dust has been found to vary by job
      and work area. Thus, the use of nonspecific dust exposure levels in epidemiologic
      studies may introduce exposure misclassification when assessing wood-related
      health effects. To improve exposure assessment in a retrospective cohort of
      28,000 sawmill workers, we developed and evaluated the validity of two empirical
      models of exposure: one for nonspecific dust and one for wood dust. The dust
      model was constructed using 1,395 dust measurements collected in 13 sawmills for
      research or regulatory purposes from 1981 to 1997. Inter-sampler conversion
      factors were used to obtain inhalable dust equivalents if necessary. The wood
      dust model was constructed after applying adjustment factors to subtract nonwood
      components of the dust from the original measurements. The validity of the two
      models was tested against measurements (n = 213) from a technologically similar
      mill that was not part of the cohort study. The proportions of variability
      explained by the dust and wood dust models were 35% and 54%, respectively. When
      tested against the validation mill, the biases in the dust model were -33% for
      outdoor jobs and 2% for indoor jobs. The biases in the wood dust model were 2%
      for outdoor jobs and -3% for indoor jobs. Strong correlations were observed
      between the predicted and observed geometric means of jobs (0.79 and 0.70 for the
      dust model and wood dust model, respectively). Testing the validity of predictive
      models examines the generalizability of the models. The low overall bias,
      especially in the wood-specific model, increases our confidence in the use of
      these models for all sawmills to assess both nonspecific particulate and wood
      related health effects in the historical cohort study.

PMID- 16298953
TI  - A section devoted to Profiles of Renown teachers and to the recognition and
      accomplishments of physiology teachers within the Society.

PMID- 16298951
TI  - The influence of common area lead hazards and lead hazard control on dust lead
      loadings in multiunit buildings.
AB  - Owners of multiunit buildings built before 1978 that have interior common areas,
      and who receive certain forms of federal assistance are generally required to
      address lead-based paint hazards in those common areas. This study examines the
      relationships between common area paint and dust lead levels and the floor dust
      lead loadings in associated dwelling units, as well as the effects of lead hazard
      control treatments in common areas. This article presents data from common areas
      in 145 low-income, mostly pre-1940, multiunit buildings with 342 associated
      dwellings in the U.S. Department of Housing and Urban Development Lead Hazard
      Control Grant Program at preintervention, clearance, and 1-year postintervention.
      Interior common areas in these multiunit buildings were not as well maintained as
      the dwellings in the buildings. At preintervention, a higher percent of the
      interior common areas had non-intact, lead-based paint on windows, doors and
      trim, and other interior components than in associated dwellings (95% versus 85%;
      78% versus 67%; and 85% versus 62%). Common areas had preintervention entry and
      interior (i.e., nonentry) floor dust lead loadings more than four times higher
      than in dwelling units (128 versus 30 micro g/ft(2); 130 versus 28 micro g/ft(2))
      while 1-year postintervention common area dust lead loadings are four to six
      times that of dwelling dust lead loadings (41 versus 11 micro g/ft(2); 44 versus
      8 micro g/ft(2)). Windowsill dust lead loadings in common areas were twice the
      loadings in dwelling units at preintervention and 1-year postintervention (756
      versus 383 mu g/ft(2); 154 versus 68 micro g/ft(2)). Interior common area
      treatments reduced geometric mean common entry dust lead loadings 71% from
      preintervention to clearance, and maintained those reduced levels from clearance
      to 1-year postintervention. Higher level interventions were not more effective
      than low-level interventions in reducing preintervention levels to clearance or 1
      year postintervention. This study demonstrates that interior common areas in the
      multiunit buildings examined contain substantial amounts of deteriorated lead
      based paint and dust. Remediation of common areas can effectively reduce those
      hazards.

PMID- 16298954
TI  - Charting a global future for education in physiology.
AB  - The 2005 Claude Bernard Distinguished Lecture was presented at the XXXV
      International Congress of Physiological Sciences (IUPS) in San Diego, CA, by Ann
      J. Sefton. Dr. Sefton is an Emeritus Professor of Physiology of the University of
      Sydney and co-Chair of the IUPS Education Committee. A full profile of Dr. Sefton
      is included in this issue's The Physiology Teacher.

PMID- 16298955
TI  - Problem-based learning and the medical school: another case of the emperor's new
      clothes?
AB  - For almost four decades, problem-based learning (PBL) has been the stated
      cornerstone of learning in many medical schools. Proponents of PBL cite the open
      nature of the learning experience where students are free to study in depth,
      unencumbered by the burdens of broad courses based on the memorization of facts;
      detractors, on the other hand, cite the lack of breadth and factual knowledge
      required for professional qualification. Both points of view have merit.
      Professional schools have a different set of needs and requirements, and it is
      these that drive the curriculum and learning philosophies. The constraints of the
      professional school are so different from those of the purely academic
      environment that PBL, while admirably suited to the latter, is just problem
      solving in the former.

PMID- 16298956
TI  - Using student feedback to construct an assessment rubric for a concept map in
      physiology.
AB  - Constructing quality assessment rubrics can be challenging, especially when they
      are used for integrated, group-centered, applied learning. We describe a
      collaborative assessment task in which groups of second-year dentistry students
      developed a complex concept map. In groups of four, the students were given a
      written, simulated, medical history of a patient and required to construct a
      concept map illustrating relevant pathophysiological concepts and pharmacological
      interventions. This report describes a research project aimed at making
      educational goals of the task more explicit through investigating student and
      faculty member understandings of the criteria that might be used to assess the
      concept map. Information was gathered about the perceptions of students in
      relation to the learning goals associated with the task. These were compared with
      faculty member perceptions. The findings were used to develop an assessment
      rubric intended to be more accessible to learners. The new rubric used the
      language of both faculty members and students to more clearly represent
      expectations of each criterion and standard. This assessment rubric will be used
      in 2005 for the next phase of the project.

PMID- 16298957
TI  - A model for understanding membrane potential using springs.
AB  - In this report, I present a simple model using springs to conceptualize the
      relationship between ionic conductances across a cellular membrane and their
      effect on membrane potential. The equation describing the relationships linking
      membrane potential, ionic equilibrium potential, and ionic conductance is of
      similar form to that describing the force generated by a spring as a function of
      its displacement. The spring analogy is especially useful in helping students to
      conceptualize the effects of multiple conductances on membrane potential.

PMID- 16298958
TI  - A capstone experiential learning exercise for undergraduate physiology laboratory
      courses.

PMID- 16298960
TI  - Proprioception: confronting prior knowledge.

PMID- 16298961
TI  - Insensible water loss during sleep: a theoretical exercise.

PMID- 16298962
TI  - International Union of Physiological Sciences teaching workshop, April 7-10,
      2005, Pali Mountain, California.
AB  - Fifty-six physiologists from fourteen countries participated in the sixth
      International Union of Physiological Sciences Teaching Workshop. The four-day
      program included a poster session, a debate on integrative versus disciplinary
      curricula, and interactive lectures on evidence-based education, inquiry
      laboratories, and student preparation for physiology courses. Participants worked
      in small groups on one of four topics: developing free web-based laboratory
      resources, information technology, curriculum planning and design, and other
      issues in classroom teaching.

PMID- 16298963
TI  - Assembly of functional hepatitis C virus glycoproteins on infectious
      pseudoparticles occurs intracellularly and requires concomitant incorporation of
      E1 and E2 glycoproteins.
AB  - Hepatitis C virus (HCV) E1 and E2 envelope glycoproteins (GPs) displayed on
      retroviral cores (HCVpp) are a powerful and highly versatile model system to
      investigate wild-type HCV entry. To further characterize this model system, the
      cellular site of HCVpp assembly and the respective roles of the HCV GPs in this
      process were investigated. By using a combination of biochemical methods with
      confocal and electron microscopic techniques, it was shown that, in cells
      producing HCVpp, both E1 and E2 colocalized with retroviral core proteins
      intracellularly, presumably in multivesicular bodies, but not at the cell
      surface. When E1 and E2 were expressed individually with retroviral core
      proteins, only E2 colocalized with and was incorporated on retroviral cores.
      Conversely, the colocalization of E1 with retroviral core proteins and its
      efficient incorporation occurred only upon co-expression of E2. Moreover, HCVpp
      infectivity correlated strictly with the presence of both E1 and E2 on retroviral
      cores. Altogether, these results confirm that the E1E2 heterodimer constitutes
      the prebudding form of functional HCV GPs and, more specifically, show that
      dimerization with E2 is a prerequisite for efficient E1 incorporation onto
      particles.

PMID- 16298964
TI  - Fluorescently tagged canine adenovirus via modification with protein IX-enhanced
      green fluorescent protein.
AB  - Canine adenovirus type 2 (CAV2) has become an attractive vector for gene therapy
      because of its non-pathogenicity and the lack of pre-existing neutralizing
      antibodies against this virus in the human population. Additionally, this vector
      has been proposed as a conditionally replicative adenovirus agent under the
      control of an osteocalcin promoter for evaluation in a syngeneic, immunocompetent
      canine model with spontaneous osteosarcoma. In this study, a CAV2 vector labelled
      with the fluorescent capsid fusion protein IX-enhanced green fluorescent protein
      (pIX-EGFP) was developed. Expression of the fluorescent fusion-protein label in
      infected cells with proper nuclear localization, and incorporation into virions,
      could be detected. The labelled virions could be visualized by fluorescence
      microscopy; this was applicable to the tracking of CAV2 infection, as well as
      localizing the distribution of the vector in tissues. Expression of pIX-EGFP
      could be exploited to detect the replication and spread of CAV2. These results
      indicate that pIX can serve as a platform for incorporation of heterologous
      proteins in the context of a canine adenovirus xenotype. It is believed that
      capsid-labelled CAV2 has utility for vector-development studies and for
      monitoring CAV2-based oncolytic adenovirus replication.

PMID- 16298965
TI  - Both soluble and membrane-anchored forms of Felid herpesvirus 1 glycoprotein G
      function as a broad-spectrum chemokine-binding protein.
AB  - Recently, glycoprotein G (gG) of several alphaherpesviruses infecting large
      herbivores was shown to belong to a new family of chemokine-binding proteins
      (vCKBPs). In the present study, the function of Felid herpesvirus 1 (FeHV-1) gG
      as a vCKBP was investigated and the following conclusions were reached: (i) FeHV
      1 secreted gG is a high-affinity broad-spectrum vCKBP that binds CC, CXC and C
      chemokines; (ii) gG is the only vCKBP expressed by FeHV-1 that binds CCL3 and
      CXCL1; (iii) secreted gG blocks chemokine activity by preventing their
      interaction with high-affinity cellular receptors; (iv) the membrane-anchored
      form of gG expressed on the surface of infected cells is also able to bind
      chemokines; and (v) the vCKBP activity is conserved among different field
      isolates of FeHV-1. Altogether, these data demonstrate that FeHV-1 gG is a new
      member of the vCKBP-4 family. Moreover, this study is the first to demonstrate
      that gG expressed at the surface of FeHV-1-infected cells can also bind
      chemokines.

PMID- 16298966
TI  - Detection of Epstein-Barr virus BGLF4 protein kinase in virus replication
      compartments and virus particles.
AB  - BGLF4 is the only serine/threonine protein kinase identified in Epstein-Barr
      virus (EBV); it is known to phosphorylate viral DNA polymerase processivity
      factor, EA-D (BMRF1), EBNA-LP, EBNA-2, cellular EF-1delta and nucleoside analogue
      ganciclovir. However, the expression and biological functions of BGLF4 have not
      yet been clearly demonstrated in EBV-infected cells. To reveal authentic
      functions of BGLF4 protein within viral-replicating cells, a panel of specific
      monoclonal antibodies was generated and characterized. The major immunogenic
      regions of BGLF4 were mapped to aa 27-70 and 327-429. Using these antibodies, the
      expression kinetics and localization of BGLF4 were analysed in reactivated EBV
      positive lymphoid and epithelial cells. BGLF4 was expressed as a phosphoprotein
      at the early lytic stage and was detected predominantly in the nucleus of EBV
      positive cells, but small amounts of BGLF4 were observed in cytosolic and heavy
      membrane fractions at the late phase of virus replication. Additionally, it was
      demonstrated that BGLF4 co-localizes with viral DNA polymerase processivity
      factor, EA-D (BMRF1), in the virus replication compartment and that it is a
      virion component. Finally, possible functional domains at the N terminus of BGLF4
      were analysed and it was found that aa 1-26 of BGLF4 are dispensable for EA-D
      phosphorylation, whereas deletion of aa 27-70 reduced kinase activity.

PMID- 16298968
TI  - Expression of the high-risk human papillomavirus type 18 and 45 E7 oncoproteins
      in cervical carcinoma biopsies.
AB  - E7 proteins are major oncoproteins of high-risk human papillomaviruses (HPVs),
      which play a key role in cervical carcinogenesis. These proteins have been shown
      to immortalize primary human cells. Due to the absence of antibodies with
      suitable sensitivity and specificity, little is known about expression of the E7
      oncoproteins in naturally infected tissues. Recently, high-level expression of
      the E7 protein of HPV-16, the most prevalent oncogenic HPV type, was demonstrated
      in cervical carcinomas by immunohistochemistry; however, approximately 15
      additional high-risk HPV types are known to be associated with cervical
      carcinoma. It is unknown whether the E7 oncoproteins of HPV-18 and -45, the
      second and third most prevalent HPV types, are expressed in cervical cancers.
      Using antibodies against HPV-18 and -45 E7 proteins, it is shown here for the
      first time that the HPV-18 and -45 E7 proteins can be detected in cervical
      carcinoma biopsies. Together with anti-HPV-16 E7 antibodies, this could create
      the possibility of detecting E7 oncoproteins in approximately 80 % of all
      cervical cancers.

PMID- 16298967
TI  - Inhibition of hepatitis B virus replication by various RNAi constructs and their
      pharmacodynamic properties.
AB  - The strategy of RNA interference (RNAi)-based gene silencing has been suggested
      to have great potential in treating viral diseases. It provides new hope of being
      able to complement the limited therapeutic options currently available for
      chronic hepatitis B virus (HBV) infection. To advance such a strategy towards
      clinical use, the effects of various parameters on the anti-HBV efficiency of
      RNAi need to be well-defined. In this study, the efficacy and pharmacodynamic
      properties of different RNAi target sequences and constructs were examined.
      Several sequences were found to be effective in cell and animal models, achieving
      inhibition rates of approximately 80-90 %. Methyl-modified small interfering RNA
      (siRNA) molecules were found to be more stable inside cells than natural siRNA
      molecules and offered longer-lasting inhibitory effects. Both were effective at
      rather low doses (an equimolar ratio with HBV preS2-S protein expression vector).
      Plasmid DNA vectors were less dose-responsive, but their effectiveness in vivo
      lasted longer, for approximately 1 month. By analysing these different parameters
      and their possible mechanisms, some important issues in RNAi therapeutics that
      should assist the future development of clinical applications have been
      addressed.

PMID- 16298969
TI  - Pushing the envelope: microinjection of Minute virus of mice into Xenopus oocytes
      causes damage to the nuclear envelope.
AB  - Parvoviruses are small DNA viruses that replicate in the nucleus of their host
      cells. It has been largely assumed that parvoviruses enter the nucleus through
      the nuclear pore complex (NPC). However, the details of this mechanism remain
      undefined. To study this problem, the parvovirus Minute virus of mice (MVM) was
      microinjected into the cytoplasm of Xenopus oocytes and a transmission electron
      microscope was used to visualize the effect of the virus on the host cell. It was
      found that MVM caused damage to the nuclear envelope (NE) in a time- and
      concentration-dependent manner. Damage was predominantly to the outer nuclear
      membrane and was often near the NPCs. However, microinjection experiments in
      which the NPCs were blocked showed that NE damage induced by MVM was independent
      of the NPC. To address the question of whether this effect of MVM is specific to
      the NE, purified organelles were incubated with MVM. Visualization by electron
      microscopy revealed that MVM did not affect all intracellular membranes. These
      data represent a novel form of virus-induced damage to host cell nuclear
      structure and suggest that MVM is imported into the nucleus using a unique
      mechanism that is independent of the NPC, and involves disruption of the NE and
      import through the resulting breaks.

PMID- 16298970
TI  - Characterization of an exochitinase from Epiphyas postvittana
      nucleopolyhedrovirus (family Baculoviridae).
AB  - Baculovirus chitinases and other family 18 glycohydrolases have been shown to
      possess both exo- and endochitinase activities when assayed against fluorescent
      chito-oligosaccharides. Homology modelling of the chitinase of Epiphyas
      postvittana nucleopolyhedrovirus (EppoNPV) against Serratia marcescens chitinase
      A indicated that the enzyme possesses an N-terminal polycystic kidney 1 (PKD1)
      domain for chitin-substrate feeding and an alpha/beta TIM barrel catalytic domain
      characteristic of a family 18 glycohydrolase. EppoNPV chitinase has many features
      in common with other baculovirus chitinases, including high amino acid identity,
      an N-terminal secretion signal and a functional C-terminal endoplasmic reticulum
      retention sequence. EppoNPV chitinase displayed exo- and endochitinolytic
      activity against fluorescent chito-oligosaccharides, with K(m) values of 270+/-60
      and 240+/-40 microM against 4MU-(GlcNAc)2 and 20+/-6 and 14+/-7 microM against
      4MU-(GlcNAc)3 for native and recombinant versions of the enzyme, respectively. In
      contrast, digestion and thin-layer chromatography analysis of short-chain
      (GlcNAc)(2-6) chito-oligosaccharides without the fluorescent 4
      methylumbelliferone (4MU) moiety produced predominantly (GlcNAc)2, indicating an
      exochitinase, although low-level endochitinase activity was detected. Digestion
      of long-chain colloidal beta-chitin and analysis by mass spectrometry identified
      a single 447 Da peak, representing a singly charged (GlcNAc)2 complexed with a
      sodium adduct ion, confirming the enzyme as an exochitinase with no detectable
      endochitinolytic activity. Furthermore, (GlcNAc)(3-6) substrates, but not
      (GlcNAc)2, acted as inhibitors of EppoNPV chitinase. Short-chain substrates are
      unlikely to interact with the aromatic residues of the PKD1 substrate-feeding
      mechanism and hence may not accurately reflect the activity of these enzymes
      against native substrates. Based upon these results, the chitinase of the
      baculovirus EppoNPV is an exochitinase.

PMID- 16298971
TI  - Type I interferons protect mice against enterovirus 71 infection.
AB  - In this study, the contribution of type I interferons (IFNs) to protection
      against infection with enterovirus 71 (EV71) was investigated using a murine
      model where the virus was administrated to neonatal Institute of Cancer Research
      (ICR) mice by either the intraperitoneal (i.p.) or the oral route. In i.p.
      inoculated mice, post-infection treatment of dexamethasone (5 mg kg(-1) at 2 or 3
      days after infection) exacerbated clinical symptoms and increased the tissue
      viral titre. In contrast, polyriboinosinic : polyribocytidylic acid [poly(I : C);
      10 or 100 microg per mouse at 12 h before infection], a potent IFN inducer,
      improved the survival rate and decreased the tissue viral titres after EV71
      challenge, which correlated with an increase in serum IFN-alpha concentration,
      the percentage of dendritic cells, their expression of major histocompatibility
      complex class II molecule and IFN-alpha in spleen. Treatment with a neutralizing
      antibody for type I IFNs (10(4) neutralizing units per mouse, 6 h before and 12 h
      after infection) resulted in frequent deaths and higher tissue viral load in
      infected mice compared with control mice. In contrast, an early administration of
      recombinant mouse IFN-alphaA (10(4) U per mouse for 3 days starting at 0, 1 or 3
      days after infection) protected the mice against EV71 infection. In vitro
      analysis of virus-induced death in three human cell lines showed that human type
      I IFNs exerted a direct protective effect on EV71. It was concluded that type I
      IFNs play an important role in controlling EV71 infection and replication.

PMID- 16298972
TI  - Coxsackie B virus infection of mice: inoculation by the oral route protects the
      pancreas from damage, but not from infection.
AB  - The pathogenesis of coxsackie B virus (CVB) infections is generally studied in
      mice by intraperitoneal (i.p.) injection, whereas the gastrointestinal tract is
      the natural porte d'entree in humans. The present study was undertaken to compare
      systematically the influence of infection route on morbidity and pathology. Swiss
      Albino mice were infected with CVB3 (Nancy) at different doses (5 x 10(3), 5 x
      10(5), 5 x 10(7), 5 x 10(9) TCID50), given either i.p. or orally. Virus could be
      isolated from several organs (heart, spleen and pancreas), indicating systemic
      infection, irrespective of the infection route. Virus titres were 1-2 logs higher
      after i.p. infection, but kinetics were largely independent of infection route.
      Organs became negative for virus isolation after 21 days, with the exception of
      spleen tissue, which remained positive for up to 49 days. Thereafter, virus was
      detected only by immunohistochemistry and PCR up to 98 days post-infection (oral
      route). Histopathology showed mild inflammation and necrosis in heart tissue of
      all mice during the acute phase, with repair at later stages. Strikingly,
      pancreatic lesions were confined to the exocrine pancreas and observed only after
      i.p. infection. Under all experimental conditions, the pancreatic islets were
      spared. In contrast, immunohistochemistry showed the presence of viral VP1,
      protein 3A and alpha interferon (IFN-alpha) in exocrine as well as endocrine
      pancreas of all mice, irrespective of route and dose of infection. It is
      concluded that infection via the oral route protects the pancreas from damage,
      but not from infection, a process in which IFN-alpha is not the only factor
      involved.

PMID- 16298973
TI  - Recombination in circulating Human enterovirus B: independent evolution of
      structural and non-structural genome regions.
AB  - The complete nucleotide sequences of eight Human enterovirus B (HEV-B) strains
      were determined, representing five serotypes, E6, E7, E11, CVB3 and CVB5, which
      were isolated in the former Soviet Union between 1998 and 2002. All strains were
      mosaic recombinants and only the VP2-VP3-VP1 genome region was similar to that of
      the corresponding prototype HEV-B strains. In seven of the eight strains studied,
      the 2C-3D genome region was most similar to the prototype E30, EV74 and EV75
      strains, whilst the remaining strain was most similar to the prototype E1 and E9
      strains in the non-structural protein genome region. Most viruses also bore marks
      of additional recombination events in this part of the genome. In the 5' non
      translated region, all strains were more similar to the prototype E9 than to
      other enteroviruses. In most cases, recombination mapped to the VP4 and 2ABC
      genome regions. This, together with the star-like topology of the phylogenetic
      trees for these genome regions, identified these genome parts as recombination
      hot spots. These findings further support the concept of independent evolution of
      enterovirus genome fragments and indicate a requirement for more advanced typing
      approaches. A range of available phylogenetic methods was also compared for
      efficient detection of recombination in enteroviruses.

PMID- 16298974
TI  - Structural proteins of Hepatitis C virus induce interleukin 8 production and
      apoptosis in human endothelial cells.
AB  - Hepatitis C virus (HCV) infection is associated with inflammation of liver
      endothelium, which contributes to the pathogenesis of chronic hepatitis. The
      mechanism of this endothelitis is not understood, since the virus does not appear
      to infect endothelial cells productively. Here, an 'innocent bystander' mechanism
      related to HCV proteins was hypothesized and it was investigated whether the
      binding of HCV particles to human endothelium induced functional changes in the
      cells. Exposure of human umbilical vein endothelial cells (HUVECs) to HCV-like
      particles (HCV-LPs) resulted in increased interleukin 8 (IL8) production and
      induction of apoptosis. The IL8 supernatants collected after stimulation of
      HUVECs with HCV-LPs, BV-GUS (control baculovirus containing beta-glucuronidase)
      and appropriate controls were used to assay the transendothelial migration of
      neutrophils. This assay confirmed that HCV-LP-induced IL8 was functionally
      active. Using specific NF-kappaB inhibitors, it was also shown that HCV-LP
      induced NF-kappaB activity mediated IL8 production in HUVECs. Apoptosis appeared
      to be mediated by the Fas/Fas-L pathway, as neutralizing antibodies for Fas and
      Fas-L significantly protected HUVECs against HCV-LP-induced apoptosis. Treatment
      of HUVECs with HCV-LPs also enhanced cellular Fas-L expression and augmented
      caspase-3 activation. This was confirmed by using a specific caspase-3 inhibitor,
      Z-Asp-Glu-Val-Asp-fluoromethyl ketone. As shown by blocking of specific chemokine
      receptors for IL8 on HUVECs, the induction of IL8 did not appear to contribute to
      HCV-LP-induced apoptosis. These results suggest that HCV proteins can trigger the
      release of inflammatory chemokines such as IL8 and cause endothelial apoptosis,
      thereby facilitating endothelitis.

PMID- 16298975
TI  - Subcellular localization of the severe acute respiratory syndrome coronavirus
      nucleocapsid protein.
AB  - The coronavirus nucleocapsid (N) protein is a viral RNA-binding protein with
      multiple functions in terms of virus replication and modulating cell signalling
      pathways. N protein is composed of three distinct regions containing RNA-binding
      motif(s), and appropriate signals for modulating cell signalling. The subcellular
      localization of severe acute respiratory syndrome coronavirus (SARS-CoV) N
      protein was studied. In infected cells, SARS-CoV N protein localized exclusively
      to the cytoplasm. In contrast to the avian coronavirus N protein, overexpressed
      SARS-CoV N protein remained principally localized to the cytoplasm, with very few
      cells exhibiting nucleolar localization. Bioinformatic analysis and deletion
      mutagenesis coupled to confocal microscopy and live-cell imaging, revealed that
      SARS-CoV N protein regions I and III contained nuclear localization signals and
      region II contained a nucleolar retention signal. However, cytoplasmic
      localization was directed by region III and was the dominant localization signal
      in the protein.

PMID- 16298976
TI  - Rare earth ions block the ion pores generated by the class II fusion proteins of
      alphaviruses and allow analysis of the biological functions of these pores.
AB  - Recently, class II fusion proteins have been identified on the surface of alpha-
      and flaviviruses. These proteins have two functions besides membrane fusion: they
      generate an isometric lattice on the viral surface and they form ion-permeable
      pores at low pH. An attempt was made to identify inhibitors for the ion pores
      generated by the fusion proteins of the alphaviruses Semliki Forest virus and
      Sindbis virus. These pores can be detected and analysed in three situations: (i)
      in the target membrane during virus entry, by performing patch-clamp measurements
      of membrane currents; (ii) in the virus particle, by studying the entry of
      propidium iodide; and (iii) in the plasma membrane of infected cells, by Fura-2
      fluorescence imaging of Ca2+ entry into infected cells. It is shown here that, at
      a concentration of 0.1 mM, rare earth ions block the ion permeability of
      alphavirus ion pores in all three situations. Even at a concentration of 0.5 mM,
      these ions do not block formation of the viral fusion pore, as they do not
      inhibit entry or multiplication of alphaviruses. The data indicate that ions flow
      through the ion pores into the virus particle in the endosome and from the
      endosome into the cytoplasm after fusion of the viral envelope with the endosomal
      membrane. These ion flows, however, are not necessary for productive infection.
      The possibility that the ability of class II fusion proteins to form ion
      permeable pores reflects their origin from protein toxins that form ion-permeable
      pores, and that entry via class II fusion proteins may resemble the entry of non
      enveloped viruses, is discussed.

PMID- 16298977
TI  - Analysis of the full-length genome of hepatitis E virus isolates obtained from
      wild boars in Japan.
AB  - Two (2.3 %) of 87 wild-caught boars in Japan had detectable hepatitis E virus
      (HEV) RNA. The two boar HEV isolates (wbJTS1 and wbJYG1) obtained in the present
      study and a previously reported isolate (wbJSG1) whose partial sequence had been
      determined were sequenced over the entire genome. The wbJSG1, wbJTS1 and wbJYG1
      isolates comprised 7225 or 7226 nt, excluding the poly(A) tail, and segregated
      into genotype 3. They differed by 8.5-11.2 % from each other and by 8.6-18.4 %
      from 17 reported genotype 3 HEV isolates, including one boar isolate, in the full
      length sequence. When compared with 191 reported genotype 3 HEV isolates whose
      partial sequences were known, these three boar isolates were closer to Japanese
      isolates than to isolates of non-Japanese origin (89.2+/-2.6 vs 85.9+/-2.2 %;
      P<0.0001). A proportion of wild boars in Japan are infected with markedly
      heterogeneous HEV strains that are indigenous to Japan and may serve as
      reservoirs of HEV.

PMID- 16298978
TI  - Presence of broadly reactive and group-specific neutralizing epitopes on newly
      described isolates of Crimean-Congo hemorrhagic fever virus.
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the genus Nairovirus
      of the family Bunyaviridae, causes severe disease in humans with high rates of
      mortality. The virus has a tripartite genome composed of a small (S), a medium
      (M) and a large (L) RNA segment; the M segment encodes the two viral
      glycoproteins, G(N) and G(C). Whilst relatively few full-length M segment
      sequences are available, it is apparent that both G(N) and G(C) may exhibit
      significant sequence diversity. It is unknown whether considerable antigenic
      differences exist between divergent CCHFV strains, or whether there are conserved
      neutralizing epitopes. The M segments derived from viral isolates of a human case
      of CCHF in South Africa (SPU 41/84), an infected tick (Hyalomma marginatum) in
      South Africa (SPU 128/81), a human case in Congo (UG 3010), an infected
      individual in Uzbekistan (U2-2-002) and an infected tick (Hyalomma asiaticum) in
      China (Hy13) were sequenced fully, and the glycoproteins were expressed. These
      novel sequences showed high variability in the N-terminal region of G(N) and more
      modest differences in the remainder of G(N) and in G(C). Phylogenetic analyses
      placed these newly identified strains in three of the four previously described M
      segment groups. Studies with a panel of mAbs specific to G(N) and G(C) indicated
      that there were significant antigenic differences between the M segment groups,
      although several neutralizing epitopes in both G(N) and G(C) were conserved among
      all strains examined. Thus, the genetic diversity exhibited by CCHFV strains
      results in significant antigenic differences that will need to be taken into
      consideration for vaccine development.

PMID- 16298980
TI  - Mutational analysis of the avian pneumovirus conserved transcriptional gene start
      sequence identifying critical residues.
AB  - Seven of the eight genes in the avian pneumovirus (APV) genome contain a
      conserved 9 nt transcriptional start sequence with the virus large (L) polymerase
      gene differing from the consensus at three positions. The sequence requirements
      of the APV transcriptional gene start sequence were investigated by generating a
      series of mutations in which each of the nine conserved bases was mutated to each
      of the other three possible nucleotides in a minigenome containing two reporter
      genes. The effect of each mutation was assessed by measuring the relative levels
      of expression from the altered and unaltered gene start sequences. Mutations at
      positions 2, 7 and 9 significantly reduced transcription levels while alterations
      to position 5 had little effect. The L gene start sequence directed transcription
      at levels approximately 50 % below that of the consensus gene start sequence.
      These data suggest that there are common features in pneumovirus transcriptional
      control sequences.

PMID- 16298979
TI  - Co-evolutionary patterns of variation in small and large RNA segments of Crimean
      Congo hemorrhagic fever virus.
AB  - The genus Nairovirus of the family Bunyaviridae includes the Crimean-Congo
      haemorrhagic fever (CCHF) species group. The species is predominated by the
      hazard-group 4 pathogens, from which the name and majority of strain entries are
      derived. Additionally, the species embraces hazard-group 2 viruses that are
      classified as members by antigenic cross-reactivity. CCHF viruses have a
      tripartite RNA genome consisting of large (L), medium (M) and small (S) segments.
      Here, the sequence characterization of previously undescribed L and S segments
      from novel strains originating in the Middle East and Africa is reported. Further
      scrutiny of this data with phylogenetic tools, in the context of other publicly
      available sequence information, reveals analogous grouping patterns between the L
      and S segments. These groups correlate with the geographical distribution of
      strain isolation and indicate that the L and S segments of CCHF viruses have
      evolved together.

PMID- 16298981
TI  - Inhibition of host peripheral blood mononuclear cell proliferation ex vivo by
      Rinderpest virus.
AB  - Rinderpest, or cattle plague, is caused by Rinderpest virus (RPV), which is
      related most closely to human Measles virus (MV), both being members of the genus
      Morbillivirus, a group of viruses known to have strong immunosuppressive effects
      in vitro and in vivo. Here, it was shown that peripheral blood mononuclear cells
      (PBMCs) isolated from cattle experimentally infected with either wild-type or
      vaccine strains of RPV impaired the proliferation of PBMCs derived from
      uninfected animals; however, in contrast to either mild or virulent strains of
      wild-type virus, the inhibition induced by the vaccine was both weak and
      transient. Flow-cytometric analysis of PBMCs obtained from cattle infected with
      different strains of RPV showed that the proportion of infected cells was virus
      dose-dependent and correlated with lymphoproliferative suppression.

PMID- 16298982
TI  - Membrane deformations induced by the matrix protein of vesicular stomatitis virus
      in a minimal system.
AB  - The matrix (M) protein of vesicular stomatitis virus plays a key role in both
      assembly and budding of progeny virions. In vitro experiments have shown a strong
      propensity of M protein to bind to vesicles containing negatively charged
      phospholipids. In vivo, it has also been demonstrated that recruitment of some
      cellular proteins by M protein is required for efficient virus budding and
      release of newly synthesized virions in the extracellular medium. The ability of
      M protein to deform target membranes in vitro was investigated in this study. It
      was shown that incubation of purified M protein with giant unilamellar vesicles
      results in the formation of patches of M protein at their surface, followed by
      deformations of the membrane toward the inside of the vesicle, which could be
      observed in phase-contrast microscopy. This provides the first evidence that M
      protein alone is able to impose the correct budding curvature on the membrane.
      Using confocal microscopy, patches of M protein that colocalized with negatively
      charged lipid domains a few minutes after vesicle injection were observed. After
      a longer incubation period, membrane deformations appeared in these domains. At
      this time, a strict colocalization of M protein, negatively charged lipids and
      membrane deformation was observed. The influence on this process of the basic N
      terminal part of the protein and of the previously identified hydrophobic loop
      has also been investigated. Interestingly, the final fission event has never been
      observed in our experimental system, indicating that other partners are required
      for this step.

PMID- 16298983
TI  - Effective treatment of retrovirus-induced suppression of antibody responses with
      CpG oligodeoxynucleotides.
AB  - Most retroviruses induce severe immunosuppression during acute infection. We have
      used the Friend retrovirus mouse model to demonstrate that immunostimulatory B
      type CpG oligodeoxynucleotides (ODN) have a protective effect against retrovirus
      induced suppression of antibody responses to potent B-cell antigens. CD8+ T cells
      were critical for effective treatment with CpG-ODN, since in vivo depletion of
      these cells from treated mice impaired protection from retrovirus-induced
      immunosuppression. Protection also required IFN-gamma, as neutralization of this
      cytokine abolished the therapeutic effect of CpG-ODN. These findings may have
      implications for the treatment of immunosuppressive virus infections.

PMID- 16298985
TI  - Evaluation of CD8+ T-cell and antibody responses following transient increased
      viraemia in rhesus macaques infected with live, attenuated simian
      immunodeficiency virus.
AB  - In vivo depletion of CD8+ T cells results in an increase in viral load in
      macaques chronically infected with simian immunodeficiency virus
      (SIVmac239deltanef). Here, the cellular and humoral immune responses associated
      with this transient period of enhanced viraemia in macaques infected with
      SIVmac239deltanef were characterized. Fourteen days after in vivo CD8+ T-cell
      depletion, two of six macaques experienced a 1-2 log10 increase in anti-gp130 and
      p27 antibody titres and a three- to fivefold increase in gamma interferon
      ecreting SIV-specific CD8+ T cells. Three other macaques had modest or no
      increase in anti-gp130 antibodies and significantly lower titres of anti-p27
      antibodies, with minimal induction of functional CD8+ T cells. Four of the five
      CD8-depleted macaques experienced an increase in neutralizing antibody titres to
      SIVmac239. Induction of SIV-specific immune responses was associated with
      increases in CD8+ T-cell proliferation and fluctuations in the levels of signal
      joint T-cell receptor excision circles in peripheral blood cells. Five months
      after CD8+ T-cell depletion, only the two high-responding macaques were protected
      from intravenous challenge with pathogenic SIV, whilst the remaining animals were
      unable to control replication of the challenge virus. Together, these findings
      suggest that a transient period of enhanced antigenaemia during chronic SIV
      infection may serve to augment virus-specific immunity in some, but not all,
      macaques. These findings have relevance for induction of human immunodeficiency
      virus (HIV)-specific immune responses during prophylactic and therapeutic
      vaccination and for immunological evaluation of structured treatment
      interruptions in patients chronically infected with HIV-1.

PMID- 16298984
TI  - The majority of human immunodeficiency virus type 1 particles present within
      splenic germinal centres are produced locally.
AB  - In most stages of human immunodeficiency virus (HIV) infection, cell-free viral
      particles can be detected in germinal centres (GCs) that are principally
      retained, in the form of immune complexes, on the surface of follicular dendritic
      cells (FDCs). The source of this virus remains unknown, although it is agreed
      that the FDCs themselves are not infected productively. By sequencing HIV viral
      DNA, genomic RNA and spliced mRNA isolated from individual splenic white pulps,
      it was shown here that the majority of HIV-1 viral particles are produced locally
      within the supporting lymphoid structure and do not result from trapping of
      circulating viruses or immune complexes. These findings underline the exquisite
      spatial organization of HIV-1 replication in vivo, suggesting a local origin for
      viruses trapped in splenic GCs.

PMID- 16298987
TI  - Rotaviruses interact with alpha4beta7 and alpha4beta1 integrins by binding the
      same integrin domains as natural ligands.
AB  - Group A rotaviruses are major intestinal pathogens that express potential
      alpha4beta1 and alpha4beta7 integrin ligand sequences Leu-Asp-Val and Leu-Asp-Ile
      in their outer capsid protein VP7, and Ile-Asp-Ala in their spike protein VP4.
      Monkey rotavirus SA11 can use recombinant alpha4beta1 as a cellular receptor. In
      this study a new potential alpha4beta1, alpha4beta7 and alpha9beta1 integrin
      ligand sequence, Tyr-Gly-Leu, was identified in VP4. It was shown that several
      human and monkey rotaviruses bound alpha4beta1 and alpha4beta7, but not
      alpha9beta1. Binding to alpha4beta1 mediated the infectivity and growth of monkey
      rotaviruses, and binding to alpha4beta7 mediated their infectivity. A porcine
      rotavirus interacted with alpha4 integrins at a post-binding stage to facilitate
      infection. Activation of alpha4beta1 increased rotavirus infectivity. Cellular
      treatment with peptides containing the alpha4 integrin ligand sequences Tyr-Gly
      Leu and Ile-Asp-Ala eliminated virus binding to alpha4 integrins and infectivity.
      In contrast, rotavirus recognition of alpha4 integrins was unaffected by a
      peptide containing the sequence Leu-Asp-Val or by a mutation in the VP7 Leu-Asp
      Val sequence. VP4 involvement in rotavirus recognition of alpha4beta1 was
      demonstrated with rotavirus reassortants. Swapping and point mutagenesis of
      alpha4 surface loops showed that rotaviruses required the same alpha4 residues
      and domains for binding as the natural alpha4 integrin ligands: mucosal addressin
      cell adhesion molecule-1, fibronectin and vascular cell adhesion molecule-1.
      Several rotaviruses are able to use alpha4beta7 and alpha4beta1 for cell binding
      or entry, through the recognition of the same alpha4-subunit domains as natural
      alpha4 ligands.

PMID- 16298986
TI  - Evolution of human immunodeficiency virus type 2 coreceptor usage, autologous
      neutralization, envelope sequence and glycosylation.
AB  - To investigate why human immunodeficiency virus type 2 (HIV-2) is less virulent
      than HIV-1, the evolution of coreceptor usage, autologous neutralization,
      envelope sequence and glycosylation was studied in sequentially obtained virus
      isolates and sera from four HIV-2-infected individuals. Neutralization of primary
      HIV-2 isolates was tested by a cell line-based assay and IgG purified from
      patients' sera. Significant autologous neutralization was observed for the
      majority (39 of 54) of the HIV-2 serum-virus combinations tested, indicating that
      neutralization escape is rare in HIV-2 infection. Furthermore, sera from 18 HIV-2
      patients displayed extensive heterologous cross-neutralization when tested
      against a panel of six primary HIV-2 isolates. This indicates that HIV-2 is
      intrinsically more sensitive to antibody neutralization than HIV-1. In line with
      earlier reports, HIV-2 isolates could use several alternative receptors in
      addition to the major coreceptors CCR5 and CXCR4. Intrapatient evolution from
      CCR5 use to CXCR4 use was documented for the first time. Furthermore, CXCR4 use
      was linked to the immunological status of the patients. Thus, all CXCR4-using
      isolates, except one, were obtained from patients with CD4 counts below 200 cells
      microl(-1). Sequence analysis revealed an association between coreceptor usage
      and charge of the V3 loop of the HIV-2 envelope, as well as an association
      between the rate of disease progression and the glycosylation pattern of the
      envelope protein. Furthermore, HIV-2 isolates had fewer glycosylation sites in
      the V3 domain than HIV-1 (two to three versus four to five). It is proposed here
      that HIV-2 has a more open and accessible V3 domain than HIV-1, due to
      differences in glycan packing, and that this may explain its broader coreceptor
      usage and greater sensitivity to neutralizing antibodies.

PMID- 16298988
TI  - Yunnan orbivirus, a new orbivirus species isolated from Culex tritaeniorhynchus
      mosquitoes in China.
AB  - An orbivirus designated Yunnan orbivirus (YUOV) was isolated from Culex
      tritaeniorhynchus mosquitoes collected in the Yunnan province of China. Electron
      microscopy showed particles with typical orbivirus morphology. The YUOV genome
      was sequenced completely and compared with previously characterized orbivirus
      genomes. Significant identity scores were detected between proteins encoded by
      the segments (Seg-1 to Seg-10) of YUOV and those encoded by their homologues in
      insect-borne and tick-borne orbiviruses. Analysis of VP1 (Pol) and VP2 (T2, which
      correlates with the virus serogroup) indicated that YUOV is a new species of the
      genus Orbivirus that is unrelated to the other insect-borne orbiviruses. The
      replication of YUOV in mosquito cell lines was restricted to Aedes albopictus
      cells and the virus failed to replicate in mammalian cell lines. However,
      intraperitoneal injection of virus into naive mice resulted in productive, non
      lethal virus replication and viraemia. Infected mice developed serum neutralizing
      antibodies and were protected against a new infection challenge. Sequence
      analysis of clones from the segments encoding outer coat proteins (Seg-3 and Seg
      6) of YUOV recovered from mouse blood did not show significant changes in the
      sequences. The availability of the complete genome sequence will facilitate the
      development of sequence-specific PCR assays for the study of YUOV epidemiology in
      the field.

PMID- 16298989
TI  - RT-PCR analysis of Deformed wing virus in honeybees (Apis mellifera) and mites
      (Varroa destructor).
AB  - Deformed wing virus (DWV) is a honeybee viral pathogen either persisting as an
      inapparent infection or resulting in wing deformity. The occurrence of deformity
      is associated with the transmission of DWV through Varroa destructor during pupal
      stages. Such infections with DWV add to the pathology of V. destructor and play a
      major role in colony collapse in the course of varroosis. Using a recently
      developed RT-PCR protocol for the detection of DWV, individual bees and mites
      originating from hives differing in Varroa infestation levels and the occurrence
      of crippled bees were analysed. It was found that 100 % of both crippled and
      asymptomatic bees were positive for DWV. However, a significant difference in the
      spatial distribution of DWV between asymptomatic and crippled bees could be
      demonstrated: when analysing head, thorax and abdomen of crippled bees, all body
      parts were always strongly positive for viral sequences. In contrast, for
      asymptomatic bees viral sequences could be detected in RNA extracted from the
      thorax and/or abdomen but never in RNA extracted from the head. DWV replication
      was demonstrated in almost all DWV-positive body parts of infected bees.
      Analysing individual mites for the presence of DWV revealed that the percentage
      of DWV-positive mites differed between mite populations. In addition, it was
      demonstrated that DWV was able to replicate in some but not all mites.
      Interestingly, virus replication in mites was correlated with wing deformity. DWV
      was also detected in the larval food, implicating that in addition to
      transmission by V. destructor DWV is also transmitted by feeding.

PMID- 16298990
TI  - In vivo detection of scrapie cases from blood by infrared spectroscopy.
AB  - In the present study, infrared spectroscopy was shown to be able to distinguish
      healthy and scrapie-infected animals by analysis of the white-cell membranous
      fraction from blood. Infrared spectroscopy was able to detect not only clinical
      cases, but also animals at a preclinical stage of the disease. These findings
      suggest this technique as an accurate in vivo diagnostic tool that could be
      applied to animal as well as human samples. In addition to possibly avoiding the
      slaughter of a huge number of animals with the socio-economic consequences that
      this poses, the test could be expected to become useful in the prevention of
      human transmission by blood transfusion.

PMID- 16298992
TI  - Reactivity of apolipoprotein E4 and amyloid beta peptide: lysosomal stability and
      neurodegeneration.
AB  - We previously demonstrated that apolipoprotein E4 (apoE4) potentiates lysosomal
      leakage and apoptosis induced by amyloid beta (Abeta) peptide in cultured Neuro
      2a cells and hypothesized that the low pH of lysosomes accentuates the conversion
      of apoE4 to a molten globule, inducing reactive intermediates capable of
      destabilizing cellular membranes. Here we report that neutralizing lysosomal pH
      with bafilomycin or NH4Cl abolished the apoE4 potentiation of Abeta-induced
      lysosomal leakage and apoptosis in Neuro-2a cells. Consistent with these results,
      apoE4 at acidic pH bound more avidly to phospholipid vesicles and disrupted them
      to a greater extent than at pH 7.4. Comparison of "Arctic" mutant Abeta, which
      forms multimers, and GM6 mutant Abeta, which remains primarily monomeric, showed
      that aggregation is essential for apoE4 to potentiate Abeta-induced lysosomal
      leakage and apoptosis. Both apoE4 and Abeta1-42 had to be internalized to exert
      these effects. Blocking the low density lipoprotein receptor-related protein with
      small interfering RNA abolished the enhanced effects of apoE4 and Abeta on
      lysosomes and apoptosis. In cultured Neuro-2a cells, Abeta1-42 increased lysosome
      formation to a greater extent in apoE3- or apoE4-transfected cells than in Neo
      transfected cells, as shown by immunostaining for lysosome-associated membrane
      protein 1. Similarly, in transgenic mice expressing apoE and amyloid precursor
      protein, hippocampal neurons displayed increased numbers of lysosomes. Thus,
      apoE4 and Abeta1-42 may work in concert in neurons to increase lysosome formation
      while increasing the susceptibility of lysosomal membranes to disruption, release
      of lysosomal enzymes into the cytosol, and neuronal degeneration.

PMID- 16298991
TI  - Regulation through the RNA polymerase secondary channel. Structural and
      functional variability of the coiled-coil transcription factors.
AB  - Gre factors enhance the intrinsic endonucleolytic activity of RNA polymerase to
      rescue arrested transcription complexes and are thought to confer the high
      fidelity and processivity of RNA synthesis. The Gre factors insert the extended
      alpha-helical coiled-coil domains into the RNA polymerase secondary channel to
      position two invariant acidic residues at the coiled-coil tip near the active
      site to stabilize the catalytic metal ion. Gfh1, a GreA homolog from Thermus
      thermophilus, inhibits rather than activates RNA cleavage. Here we report the
      structure of the T. thermophilus Gfh1 at 2.4 A resolution revealing a two-domain
      architecture closely resembling that of GreA. However, the interdomain
      orientation is strikingly distinct (approximately 162 degrees rotation) between
      the two proteins. In contrast to GreA, which has two acidic residues on a well
      fixed self-stabilized alpha-turn, the tip of the Gfh1 coiled-coil is flexible and
      contains four acidic residues. This difference is likely the key to the Gre
      functional diversity, while Gfh1 inhibits exo- and endonucleolytic cleavage, RNA
      synthesis, and pyrophosphorolysis, GreA enhances only the endonucleolytic
      cleavage. We propose that Gfh1 acidic residues stabilize the RNA polymerase
      active center in a catalytically inactive configuration through Mg2+-mediated
      interactions. The excess of the acidic residues and inherent flexibility of the
      coiled-coil tip might allow Gfh1 to adjust its activity to structurally distinct
      substrates, thereby inhibiting diverse catalytic reactions of RNA polymerase.

PMID- 16298993
TI  - Solution structure of the human ubiquitin-specific protease 15 DUSP domain.
AB  - Ubiquitin-specific proteases (USPs) can remove covalently attached ubiquitin
      moieties from target proteins and regulate both the stability and ubiquitin
      signaling state of their substrates. All USPs contain a conserved catalytic
      domain surrounded by one or more subdomains, some of which contribute to target
      recognition. One such specific subdomain, the DUSP domain (domain present in
      ubiquitin-specific proteases), is present in at least seven different human USPs
      that regulate the stability of or interact with the hypoxia-inducible
      transcription factor HIF1-alpha, the Von Hippel-Lindau protein (pVHL), cullin E3
      ligases, and BRCA2. We describe the NMR solution structure of the DUSP domain of
      human USP15, recently implicated in COP9 (constitutive photomorphogenic gene 9)
      signalosome regulation. Its tripod-like structure consists of a 3-fold alpha
      helical bundle supporting a triple-stranded anti-parallel beta-sheet. The DUSP
      domain displays a novel fold, an alpha/beta tripod (AB3). DUSP domain surface
      properties and previously described work suggest a potential role in
      protein/protein interaction or substrate recognition.

PMID- 16298994
TI  - Structural and kinetic analysis of two covalent sialosyl-enzyme intermediates on
      Trypanosoma rangeli sialidase.
AB  - Trypanosoma rangeli sialidase is a glycoside hydrolase (family GH33) that
      catalyzes the cleavage of alpha-2-->3-linked sialic acid residues from
      sialoglycoconjugates with overall retention of anomeric configuration. Retaining
      glycosidases usually operate through a ping-pong mechanism, wherein a covalent
      intermediate is formed between the carbohydrate and an active site carboxylic
      acid of the enzyme. Sialidases, instead, appear to use a tyrosine as the
      catalytic nucleophile, leaving the possibility of an essentially different
      catalytic mechanism. Indeed, a direct nucleophilic role for a tyrosine was shown
      for the homologous trans-sialidase from Trypanosoma cruzi, although itself not a
      typical sialidase. Here we present the three-dimensional structures of the
      covalent glycosyl-enzyme complexes formed by the T. rangeli sialidase with two
      different mechanism-based inactivators at 1.9 and 1.7 Angstroms resolution. To
      our knowledge, these are the first reported structures of enzymatically competent
      covalent intermediates for a strictly hydrolytic sialidase. Kinetic analyses have
      been carried out on the formation and turnover of both intermediates, showing
      that structural modifications to these inactivators can be used to modify the
      lifetimes of covalent intermediates. These results provide further evidence that
      all sialidases likely operate through a similar mechanism involving the transient
      formation of a covalently sialylated enzyme. Furthermore, we believe that the
      ability to "tune" the inactivation and reactivation rates of mechanism-based
      inactivators toward specific enzymes represents an important step toward
      developing this class of inactivators into therapeutically useful compounds.

PMID- 16298995
TI  - EphB receptors regulate dendritic spine morphogenesis through the
      recruitment/phosphorylation of focal adhesion kinase and RhoA activation.
AB  - Dendritic filopodia are small protrusions on the surface of neuronal dendrites
      that transform into dendritic spines upon synaptic contact with axon terminals.
      The formation of dendritic spines is a critical aspect of synaptic development.
      Dendritic spine morphogenesis is characterized by filopodia shortening followed
      by the formation of mature mushroom-shaped spines. Here we show that activation
      of the EphB receptor tyrosine kinases in cultured hippocampal neurons by their
      ephrinB ligands induces morphogenesis of dendritic filopodia into dendritic
      spines. This appears to occur through assembly of an EphB-associated protein
      complex that includes focal adhesion kinase (FAK), Src, Grb2, and paxillin and
      the subsequent activations of FAK, Src, paxillin, and RhoA. Furthermore, Cre
      mediated knock-out of loxP-flanked fak or RhoA inhibition blocks EphB-mediated
      morphogenesis of dendritic filopodia. Finally, EphB-mediated RhoA activation is
      disrupted by FAK knock-down. These data suggest that EphB receptors are upstream
      regulators of FAK in dendritic filopodia and that FAK-mediated RhoA activation
      contributes to assembly of actin filaments in dendritic spines.

PMID- 16298996
TI  - Effect of Mg2+ on the DNA binding modes of the Streptococcus pneumoniae SsbA and
      SsbB proteins.
AB  - The effect of Mg2+ on the binding of the Streptococcus pneumoniae single-stranded
      DNA binding (SSB) proteins, SsbA and SsbB, to various dT(n) oligomers was
      examined by polyacrylamide gel electrophoresis. The results were then compared
      with those that were obtained with the well characterized SSB protein from
      Escherichia coli, SsbEc. In the absence of Mg2+, the results indicated that the
      SsbEc protein was able to bind to the dT(n) oligomers in the SSB(35) mode, with
      only two of the four subunits of the tetramer interacting with the dT(n)
      oligomers. In the presence of Mg2+, however, the results indicated that the SsbEc
      protein was bound to the dT(n) oligomers in the SSB(65) mode, with all four
      subunits of the tetramer interacting with the dT(n) oligomers. The SsbA protein
      behaved similarly to the SsbEc protein under all conditions, indicating that it
      undergoes Mg2+ -dependent changes in its DNA binding modes that are analogous to
      those of the SsbEc protein. The SsbB protein, in contrast, appeared to bind to
      the dT(n) oligomers in an SSB(65)-like mode in either the presence or the absence
      of Mg2+, suggesting that it may not exhibit the pronounced negative intrasubunit
      cooperativity in the absence of Mg2+ that is required for the formation of the
      SSB(35) mode. Additional experiments with a chimeric SsbA/B protein indicated
      that the structural determinants that govern the transitions between the
      different DNA binding modes may be contained within the N-terminal domains of the
      SSB proteins.

PMID- 16298998
TI  - A novel protease inhibitor of the alpha2-macroglobulin family expressed in the
      human epidermis.
AB  - In the course of a large scale analysis of late-expressed genes in the human
      epidermis, we identified a new member of the alpha(2)-macroglobulin (alpha2M)
      protease inhibitor family, A2ML1 (for alpha(2)-macroglobulin-like 1). Like A2M
      and PZP, A2ML1 is located on chromosome 12p13.31. A2ML1 encodes a protein of 1454
      amino acids, which fits the characteristics of alpha2Ms: 1) strong conservation
      in amino acid sequence including most of cysteine positions with alpha2M; 2) a
      putative central bait domain; 3) a typical thiol ester sequence. Northern blot
      and reverse transcriptase-PCR studies revealed a single 5-kb A2ML1 mRNA, mainly
      in the epidermis granular keratinocytes. A2ML1 is also transcribed in placenta,
      thymus, and testis. By Western blot analysis, alpha2ML1 is detected as a
      monomeric, approximately 180-kDa protein in human epidermis. In vitro
      keratinocyte differentiation is associated with increased expression levels. By
      immunohistochemistry, alpha2ML1 was detected within keratinosomes in the granular
      layer of the epidermis, and as a secreted product in the extracellular space
      between the uppermost granular layer and the cornified layer. Recombinant
      alpha2ML1 displayed inhibitory activity toward chymotrypsin, papain, thermolysin,
      subtilisin A, and to a lesser extent, elastase but not trypsin. Incubation with
      chymotrypsin and the chymotrypsin-like kallikrein 7 protease indicated that
      alpha2ML1 binds covalently to these proteases, a feature shared with other
      members of the family. Therefore, alpha2ML1 is the first alpha2M family member
      detected in the epidermis. It may play an important role during desquamation by
      inhibiting extracellular proteases.

PMID- 16298999
TI  - Role of the kinesin-2 family protein, KIF3, during mitosis.
AB  - During mitosis, kinesin and dynein motor proteins play critical roles in the
      equal segregation of chromosomes between two daughter cells. Kinesin-2 is
      composed of two microtubule-based motor subunits, KIF3A/3B, and a kinesin
      associated protein known as KAP3, which links KIF3A/3B to cargo that is carried
      to cellular organelles along microtubules in interphase cells. We have shown here
      that the kinesin-2 complex is localized with components of the mitotic apparatus
      such as spindle microtubules and centrosomes. Furthermore, we found that
      expression of a mutant KIF3B, which is able to associate with KIF3A but not KAP3
      in NIH3T3 cells, caused chromosomal aneuploidy and abnormal spindle formation.
      Our data suggested that the kinesin-2 complex plays an important role not only in
      interphase but also in mitosis.

PMID- 16299000
TI  - Inactivation of homocitrate synthase causes lysine auxotrophy in copper/zinc
      containing superoxide dismutase-deficient yeast Schizosaccharomyces pombe.
AB  - The fission yeast Schizosaccharomyces pombe lacking copper/zinc-containing
      superoxide dismutase (CuZn-SOD) is auxotrophic for lysine and sulfurous amino
      acids under aerobic growth conditions. A multicopy suppressor gene (phx1+) that
      restored the growth of CuZn-SOD-deficient cells on minimal medium was isolated.
      It encodes a putative DNA-binding protein with a conserved homeobox domain.
      Overproduction of Phx1 increased the amount of several proteins, and one of those
      turned out to be a putative homocitrate synthase (HCS) encoded by the lys4+ gene
      in S. pombe as judged by mass spectrometric analysis. Consistent with this
      observation, overexpression of the lys4+ gene increased HCS enzyme activity and
      was sufficient to suppress the lysine requirement of the CuZn-SOD-deficient
      cells. Enzyme activity and Western blot analyses revealed that the activity and
      protein level of HCS were dramatically reduced upon depletion of CuZn-SOD.
      Treatment of exponentially growing S. pombe cells with paraquat, a superoxide
      generator, caused a decrease in the amount of Lys4 protein as expected. These
      results led us to conclude that HCS, the first enzyme in the alpha-aminoadipate
      mediated pathway for lysine synthesis common in fungi and some bacteria, is a
      labile target of oxidative stress caused by CuZn-SOD depletion and that its
      synthesis is positively regulated by the putative transcriptional regulator Phx1.

PMID- 16298997
TI  - Identification of amino acids in HIV-1 and avian sarcoma virus integrase subsites
      required for specific recognition of the long terminal repeat Ends.
AB  - A tetramer model for HIV-1 integrase (IN) with DNA representing 20 bp of the U3
      and U5 long terminal repeats (LTR) termini was assembled using structural and
      biochemical data and molecular dynamics simulations. It predicted amino acid
      residues on the enzyme surface that can interact with the LTR termini. A separate
      structural alignment of HIV-1, simian sarcoma virus (SIV), and avian sarcoma
      virus (ASV) INs predicted which of these residues were unique. To determine
      whether these residues were responsible for specific recognition of the LTR
      termini, the amino acids from ASV IN were substituted into the structurally
      equivalent positions of HIV-1 IN, and the ability of the chimeras to 3 ' process
      U5 HIV-1 or ASV duplex oligos was determined. This analysis demonstrated that
      there are multiple amino acid contacts with the LTRs and that substitution of ASV
      IN amino acids at many of the analogous positions in HIV-1 IN conferred partial
      ability to cleave ASV substrates with a concomitant loss in the ability to cleave
      the homologous HIV-1 substrate. HIV-1 IN residues that changed specificity
      include Val(72), Ser(153), Lys(160)-Ile(161), Gly(163)-Val(165), and His(171)
      Leu(172). Because a chimera that combines several of these substitutions showed a
      specificity of cleavage of the U5 ASV substrate closer to wild type ASV IN
      compared with chimeras with individual amino acid substitutions, it appears that
      the sum of the IN interactions with the LTRs determines the specificity. Finally,
      residues Ser(153) and Val(72) in HIV-1 IN are among those that change in enzymes
      that develop resistance to naphthyridine carboxamide- and diketo acid-related
      inhibitors in cells. Thus, amino acid residues involved in recognition of the
      LTRs are among these positions that change in development of drug resistance.

PMID- 16299002
TI  - From polynucleotide phosphorylase to neurobiology.

PMID- 16299001
TI  - Estrogen receptor-alpha mediates gender differences in atherosclerosis induced by
      HIV protease inhibitors.
AB  - As part of highly active antiretroviral therapy, protease inhibitor treatment has
      significantly increased the lifespan of human immunodeficiency virus (HIV)
      infected individuals. Many patients, however, develop negative side effects,
      including premature atherosclerosis. We have previously demonstrated that in male
      low density lipoprotein receptor (LDL-R) null mice, HIV protease inhibitors
      induce atherosclerotic lesions and cholesterol accumulation in macrophages in the
      absence of changes in plasma lipid levels. We determined that these increases
      were due to an up-regulation of the scavenger receptor, CD36. In the present
      study, we examined the effects of HIV protease inhibitors in female LDL-R null
      mice. Female mice given ritonavir and amprenavir (23 and 10 microg/mouse/day,
      respectively) developed fewer atherosclerotic lesions than males. Furthermore,
      peritoneal macrophages isolated from ritonavir-treated females had reduced levels
      of cholesterol accumulation as compared with males, and CD36 protein levels were
      increased to a significantly lesser degree in females than in males. To
      investigate the molecular mechanisms of this gender difference, we examined the
      effect of genetically removing estrogen receptor-alpha (ERalpha). In female mice
      lacking both LDL-R and ERalpha, the protective effect of gender was lost.
      Additionally, the reduced levels of cholesterol accumulation in macrophages
      observed in females was reversed. Furthermore, the absence of ERalpha resulted in
      increased expression of CD36 protein in a macrophage-specific manner in mice
      treated with ritonavir. These data demonstrate that ERalpha is directly involved
      in the regulation of cholesterol metabolism in macrophages and plays an important
      role in the gender differences observed in HIV protease inhibitor-induced
      atherosclerosis.

PMID- 16299004
TI  - Leaf life span plasticity in tropical seedlings grown under contrasting light
      regimes.
AB  - BACKGROUND AND AIMS: The phenotypic plasticity of leaf life span in response to
      low resource conditions has a potentially large impact on the plant carbon
      budget, notably in evergreen species not subject to seasonal leaf shedding, but
      has rarely been well documented. This study evaluates the plasticity of leaf
      longevity, in terms of its quantitative importance to the plant carbon balance
      under limiting light. METHODS: Seedlings of four tropical tree species with
      contrasting light requirements (Alstonia scholaris, Hevea brasiliensis, Durio
      zibethinus and Lansium domesticum) were grown under three light regimes (full
      sunlight, 45 % sunlight and 12 % sunlight). Their leaf dynamics were monitored
      over 18 months. RESULTS: All species showed a considerable level of plasticity
      with regard to leaf life span: over the range of light levels explored, the ratio
      of the range to the mean value of life span varied from 29 %, for the least
      plastic species, to 84 %, for the most. The common trend was for leaf life span
      to increase with decreasing light intensity. The plasticity apparent in leaf life
      span was similar in magnitude to the plasticity observed in specific leaf area
      and photosynthetic rate, implying that it has a significant impact on carbon gain
      efficiency when plants acclimate to different light regimes. In all species,
      median survival time was negatively correlated with leaf photosynthetic capacity
      (or its proxy, the nitrogen content per unit area) and leaf emergence rate.
      CONCLUSIONS: Longer leaf life spans under low light are likely to be a
      consequence of slower ageing as a result of a slower photosynthetic metabolism.

PMID- 16299005
TI  - Comparison of pollen transfer dynamics by multiple floral visitors: experiments
      with pollen and fluorescent dye.
AB  - BACKGROUND AND AIMS: Most plant species are visited by a diversity of floral
      visitors. Pollen transfer of the four most common pollinating bee species and one
      nectar-robbing bee of the distylous plant Gelsemium sempervirens were compared.
      METHODS: Naturally occurring pollen loads carried by the common floral visitor
      species of G. sempervirens were compared. In addition, dyed pollen donor flowers
      and sequences of four emasculated recipient flowers in field cages were used to
      estimate pollen transfer, and the utility of fluorescent dye powder as an
      analogue for pollen transfer was determined. KEY RESULTS: Xylocopa virginica,
      Osmia lignaria and Habropoda laboriosa carried the most G. sempervirens pollen on
      their bodies, followed by Bombus bimaculatus and Apis mellifera. However, B.
      bimaculatus, O. lignaria and H. laboriosa transferred significantly more pollen
      than A. mellifera. Nectar-robbing X. virginica transferred the least pollen, even
      when visiting legitimately. Dye particles were strongly correlated with pollen
      grains on a stigma, and therefore provide a good analogue for pollen in this
      system. The ratio of pollen : dye across stigmas was not affected by bee species
      or interactions between bee species and floral morphology. However, dye transfer
      was more sensitive than pollen transfer to differences in floral morphology.
      CONCLUSIONS: The results from this study add to a growing body of literature
      highlighting that floral visitors vary in pollination effectiveness, and that
      visitors carrying the most pollen on their bodies may not always be the most
      efficient at depositing pollen on stigmas. Understanding the magnitude of
      variability in pollinator quality is one important factor for predicting how
      different pollinator taxa may influence the evolution of floral traits.

PMID- 16299003
TI  - A novel function of abscisic acid in the regulation of rice (Oryza sativa L.)
      root growth and development.
AB  - Plant roots retain developmental plasticity and respond to environmental stresses
      or exogenous plant growth regulators by undergoing profound morphological and
      physiological alteration. In this study, we investigated the effects of exogenous
      ABA on root growth and development in Taichung native 1 (TN1) rice. Exogenous
      application of 10 microM ABA leads to swelling, root hair formation and
      initiation of lateral root primodia in the tips of young, seminal rice roots.
      Cortex cells increased in size and were irregularly shaped. ABA treatment
      significantly increased 2, 3, 5-triphenyl tetrazolium chloride (TTC) reductase
      ability in the root tips and the exudation rate of xylem sap. In addition, the
      K(+) ion content in xylem sap increased nearly 2-fold, but not that of Ca(2+) or
      Mg(2+). Analysis of proteins expressed in the root tips identified several ABA
      induced or -repressed proteins, including actin depolymerization factor (ADF),
      late embryo abundant protein (LEA), putative steroid membrane-binding protein,
      ferredoxin thionine reductase and calcium-binding protein. The effects of ABA on
      root morphogenesis change were Ca(2+) dependent and required the participation of
      calmodulin and de novo protein synthesis. A model is presented that illustrates
      how ABA acts through a potential cellular and signal transduction mechanism to
      induce morphological and physiological changes in rice roots.

PMID- 16299006
TI  - A role for shoot protein in shoot-root dry matter allocation in higher plants.
AB  - BACKGROUND AND AIMS: It is stated in many recent publications that nitrate (NO3-)
      acts as a signal to regulate dry matter partitioning between the shoot and root
      of higher plants. Here we challenge this hypothesis and present evidence for the
      viewpoint that NO3- and other environmental effects on the shoot:root dry weight
      ratio (S:R) of higher plants are often related mechanistically to changes in
      shoot protein concentration. METHODS: The literature on environmental effects on
      S:R is reviewed, focusing on relationships between S:R, growth and leaf NO3- and
      protein concentrations. A series of experiments carried out to test the proposal
      that S:R is dependent on shoot protein concentration is highlighted and new data
      are presented for tobacco (Nicotiana tabacum). KEY RESULTS/EVIDENCE: Results from
      the literature and new data for tobacco show that S:R and leaf NO3- concentration
      are not significantly correlated over a range of environmental conditions. A
      mechanism involving the relative availability of C and N substrates for growth in
      shoots can explain how shoot protein concentration can influence shoot growth and
      hence root growth and S:R. Generally, results in the literature are compatible
      with the hypothesis that macronutrients, water, irradiance and CO2 affect S:R
      through changes in shoot protein concentration. In detailed studies on several
      species, including tobacco, a linear regression model incorporating leaf soluble
      protein concentration and plant dry weight could explain the greater proportion
      of the variation in S:R within and between treatments over a wide range of
      conditions. CONCLUSIONS: It is concluded that if NO3- can influence the S:R of
      higher plants, it does so only over a narrow range of conditions. Evidence is
      strong that environmental effects on S:R are often related mechanistically to
      their effects on shoot protein concentration.

PMID- 16299011
TI  - Proceedings of the 2nd International Conference on Advances in Canine and Feline
      Genomics, Utrecht, The Netherlands, October 14-16, 2004.

PMID- 16299007
TI  - Pollen-wall formation in Arum alpinum.
AB  - BACKGROUND AND AIMS: Arum alpinum has a quite uncommon pollen wall. A
      sporopolleninous ektexine is missing. The outermost pollen wall layer is formed
      by the endexine which is covered by polysaccharidic ornamentation elements. An
      ontogenetical investigation was accomplished to clarify pollen-wall development,
      with special reference to callose and pollen-wall development. METHODS: Plants of
      Arum alpinum grown in their natural habitat were collected once a week within the
      vegetative period and processed for semi- and ultra-thin sectioning. KEY RESULTS:
      At any stage of pollen-wall formation callose is missing. Microspores are
      released from the tetrad by invagination of the amoeboid tapetum. The
      polysaccharidic wall ornamentations are formed by the tapetum. CONCLUSIONS: There
      appears to be no truth in the dogma that callose is essential for microspore
      separation and release from the tetrad. The lack of callose does not influence
      fertility but could be the reason for the uncommon pollen wall, where a
      sporopolleninous ektexine is missing.

PMID- 16299013
TI  - Effect of comorbidities and postoperative complications on mortality after hip
      fracture in elderly people: prospective observational cohort study.
AB  - OBJECTIVES: To evaluate postoperative medical complications and the association
      between these complications and mortality at 30 days and one year after surgery
      for hip fracture and to examine the association between preoperative comorbidity
      and the risk of postoperative complications and mortality. DESIGN: Prospective
      observational cohort study. SETTING: University teaching hospital. PARTICIPANTS:
      2448 consecutive patients admitted with an acute hip fracture over a four year
      period. We excluded 358 patients: all those aged < 60; those with periprosthetic
      fractures, pathological fractures, and fractures treated without surgery; and
      patients who died before surgery. INTERVENTIONS: Routine care for hip fractures.
      MAIN OUTCOME MEASURES: Postoperative complications and mortality at 30 days and
      one year. RESULTS: Mortality was 9.6% at 30 days and 33% at one year. The most
      common postoperative complications were chest infection (9%) and heart failure
      (5%). In patients who developed postoperative heart failure mortality was 65% at
      30 days (hazard ratio 16.1, 95% confidence interval 12.2 to 21.3). Of these
      patients, 92% were dead by one year (11.3, 9.1 to 14.0). In patients who
      developed a postoperative chest infection mortality at 30 days was 43% (8.5, 6.6
      to 11.1). Significant preoperative variables for increased mortality at 30 days
      included the presence of three or more comorbidities (2.5, 1.6 to 3.9),
      respiratory disease (1.8, 1.3 to 2.5), and malignancy (1.5, 1.01 to 2.3).
      CONCLUSIONS: In elderly people with hip fracture, the presence of three or more
      comorbidities is the strongest preoperative risk factor. Chest infection and
      heart failure are the most common postoperative complications and lead to
      increased mortality. These groups offer a clear target for specialist medical
      assessment.

PMID- 16299012
TI  - Time trends in primary resistance to HIV drugs in the United Kingdom: multicentre
      observational study.
AB  - OBJECTIVE: To examine whether the level of primary resistance to HIV drugs is
      increasing in the United Kingdom. DESIGN: Multicentre observational study.
      SETTING: All virology laboratories in the United Kingdom carrying out tests for
      HIV resistance as part of routine clinical care. PARTICIPANTS: 2357 people
      infected with HIV who were tested for resistance before receiving antiretroviral
      therapy. MAIN OUTCOME MEASURE: Prevalence of drug resistance on basis of the
      Stanford genotypic interpretation system. RESULTS: Over the study period
      (February 1996 to May 2003), 335 (14.2%, 95% confidence interval 12.8% to 15.7%)
      samples had mutations that conferred resistance to one or more antiretroviral
      drugs (9.3% high level resistance, 5.9% medium level resistance). The prevalence
      of primary resistance has increased markedly over time, although patterns are
      specific to drug class; the largest increase was for non-nucleoside reverse
      transcriptase inhibitors. In 2002-3, the prevalence of resistance to any
      antiretroviral drug to nucleoside or nucleotide reverse transcriptase inhibitors,
      to non-nucleoside reverse transcriptase inhibitors, or to protease inhibitors was
      19.2% (15.7% to 23.2%), 12.4% (9.5% to 15.9%), 8.1% (5.8% to 11.1%), and 6.6%
      (4.4% to 9.3%), respectively. The risk of primary resistance was only weakly
      related to most demographic and clinical factors, including ethnicity and viral
      subtype. CONCLUSIONS: The United Kingdom has one of the highest reported rates of
      primary resistance to HIV drugs worldwide. Prevalence seems still to be
      increasing and is high in all demographic subgroups.

PMID- 16299014
TI  - The cognitive cost of being a twin: evidence from comparisons within families in
      the Aberdeen children of the 1950s cohort study.
AB  - OBJECTIVES: To determine whether twins have lower IQ scores in childhood than
      singletons in the same family and, if so, whether differences in fetal growth
      explain this deficit. DESIGN: Cohort study. SETTING: Scotland. PARTICIPANTS: 9832
      singletons and 236 twins born in Aberdeen between 1950 and 1956. RESULTS: At age
      7, the mean IQ score of twins was 5.3 points lower (95% confidence interval 1.5
      to 9.1) and at age 9, 6.0 points lower (1.7 to 10.2) than that of singletons in
      the same family. Adjustment for sex, mother's age, and number of older siblings
      had little effect on these differences. Further adjustment for birth weight and
      gestational age attenuated the IQ difference between twins and singletons: the
      difference in mean IQ was 2.6 points (-1.5 to 6.7) at age 7 and 4.1 points (-0.5
      to 8.8) at age 9. CONCLUSIONS: Twins have substantially lower IQ in childhood
      than singletons in the same family. This effect cannot be explained by
      confounding due to socioeconomic, maternal, or other family characteristics, or
      by recruitment bias. The reduced prenatal growth and shorter gestations of twins
      may explain an important part of their lower IQ in childhood.

PMID- 16299015
TI  - Are experimental treatments for cancer in children superior to established
      treatments? Observational study of randomised controlled trials by the Children's
      Oncology Group.
AB  - OBJECTIVES: To assess how often new treatments for childhood cancer assessed in
      phase III randomised trials are superior or inferior to standard treatments and
      whether the pattern of successes and failures in new treatments is consistent
      with uncertainty being the ethical basis for enrolling patients in such trials.
      DESIGN: Observational study. SETTING: Phase III randomised controlled trials
      carried out under the aegis of the Children's Oncology Group between 1955 and
      1997, regardless of whether they were published. MAIN OUTCOME MEASURES: Overall
      survival, event free survival, and treatment related mortality. RESULTS: 126
      trials were included, involving 152 comparisons and 36,567 patients. The odds
      ratio for overall survival with experimental treatments was 0.96 (99% confidence
      interval 0.89 to 1.03), indicating that new treatments are as likely to be
      inferior as they are to be superior to standard treatments. This result was not
      affected by publication bias, methodological quality, treatment type, disease, or
      comparator. CONCLUSIONS: New treatments in childhood cancer tested in randomised
      controlled trials are, on average, as likely to be inferior as they are to be
      superior to standard treatments, confirming that the uncertainty principle has
      been operating.

PMID- 16299016
TI  - P2X purinoceptor subtypes on paraventricular nucleus neurones projecting to the
      rostral ventrolateral medulla in the rat.
AB  - The rostral ventrolateral medulla (RVLM) is essential for the generation of
      sympathetic nerve activity. The RVLM receives a substantial innervation from the
      hypothalamic paraventricular nucleus (PVN). Activation of P2X purinoceptors via
      ATP has been shown to mediate fast excitatory synaptic neurotransmission. There
      is mounting evidence to suggest the presence of P2X purinoceptors in hypothalamic
      nuclei, including the PVN. In this study, we determined whether P2X1-P2X6
      purinoceptor subtypes were present on PVN neurones that projected to the RVLM.
      Injection of the retrogradely transported tracer, rhodamine-tagged microspheres,
      into the pressor region of the RVLM was used to identify the neurones in the PVN
      that innervated the RVLM. P2X1-P2X6 purinoceptors were detected by
      immunohistochemistry. Double-labelled neurones were quantified and expressed as a
      proportion of the retrogradely labelled neurones. The proportions of double
      labelled neurones for each of the P2X purinoceptor subtypes varied, on average,
      from 14 to 29%. The P2X3 purinoceptor subtype was found to be the dominant
      purinoceptor subtype present on PVN neurones projecting to the RVLM. Additionally
      it was apparent that more than one P2X purinoceptor subtype was present on the
      PVN neurones projecting to the RVLM, since the sum of the average percentages of
      double-labelled neurones for each P2X purinoceptor subtype exceeded 100%. These
      findings highlight the presence of the P2X1-P2X6 purinoceptors on PVN neurones
      projecting to the RVLM. The results suggest a potential role for ATP in the PVN
      in the regulation of sympathetic nerve activity.

PMID- 16299017
TI  - Effects of short-term normobaric hypoxia on haematology, muscle phenotypes and
      physical performance in highly trained athletes.
AB  - This study aimed to determine the impact of short-term normobaric hypoxia on
      physiology and performance in highly trained athletes. Twelve (7 male and 5
      female) athletes were randomly assigned into two groups and spent 8 h per night
      for two consecutive nights a week over 3 weeks under either short-term normobaric
      hypoxia (simulating 3636 m altitude, inspired O2=13%) or in normobaric normoxia
      in a single-blind study. Following a 3 week washout period, athletes were then
      exposed to the other condition. Athletes were tested for maximal oxygen
      consumption and time to exhaustion on an electromagnetically braked cycle
      ergometer before and after each treatment in addition to being tested for
      anaerobic performance (Wingate test) on a modified Monark cycle ergometer. Blood
      samples were taken throughout the experiment and vastus lateralis muscle biopsies
      were taken before and after each treatment. Increases in red blood cell count,
      haematocrit, haemoglobin, platelet number and erythropoietin concentration were
      observed following short-term normobaric hypoxia. Except for a modest decrease in
      phosphofructokinase activity following short-term normobaric hypoxia, no changes
      were observed in muscle enzyme activities, buffer capacity, capillary density or
      morphology. No performance measures were changed following short-term normobaric
      hypoxia or normobaric normoxia. Although short-term normobaric hypoxia exposure
      increased levels of a number of haematological parameters, this was not
      associated with improved aerobic or anaerobic performance in highly trained
      athletes.

PMID- 16299019
TI  - Alpha2C-adrenoceptor polymorphism is associated with improved event-free survival
      in patients with dilated cardiomyopathy.
AB  - AIMS: The sympathetic nervous system plays a central role in cardiac growth but
      its overstimulation is associated with increased mortality in patients with
      chronic heart failure. Pre-synaptic alpha2-adrenoceptors are essential feedback
      regulators to control the release of norepinephrine from sympathetic nerves. In
      this study we tested whether a deletion polymorphism in the human alpha2C
      adrenoceptor gene (alpha2CDel322-325) affects progression of heart failure in
      patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: We genotyped and
      phenotyped 345 patients presenting with DCM in the heart transplant unit of the
      German Heart Institute, starting in 1994. Patients were treated according to
      guidelines (99% ACEI, 76% beta-blockers) and were followed until December 2002 or
      until a first event [death, heart transplantation, or implantation of a left
      ventricular assist device (LVAD) for a life-threatening condition] occurred. Mean
      follow-up time was 249 weeks (4.9 years) in event-free patients and 104 weeks (2
      years) in patients with events. During follow-up, 51% of the patients exhibited
      an event: death (18%), implantation of LVAD as bridging for transplantation (7%),
      or heart transplantation (25%). By Kaplan-Meier analysis, DCM patients with the
      deletion variant Del322-325 in the alpha2C-adrenoceptor showed significantly
      decreased event rates (P=0.0043). Cox regression analysis revealed that the
      presence of the deletion was associated with reduced death rate (relative risk:
      0.129, 95% CI: 0.18-0.9441, P=0.044) and event rates (relative risk: 0.167, 95%
      CI: 0.041-0.685, P=0.012). CONCLUSION: Alpha2C-adrenoceptor deletion may be a
      novel, strong, and independent predictor of reduced event rates in DCM patients
      treated according to guidelines.

PMID- 16299020
TI  - N-terminal brain natriuretic peptide as a screening tool for heart failure in the
      pacemaker population.
AB  - AIMS: Assessment of N-terminal brain natriuretic peptide (NT-BNP) as a screening
      tool for heart failure in patients with a permanent pacemaker. METHODS AND
      RESULTS: Consecutive patients undergoing a routine permanent pacemaker assessment
      were enrolled. Patients underwent medical history and examination,
      echocardiography and blood sampling for NT-BNP. Analysis was performed on 261
      patients (132 DDD, 121 VVI, eight others), mean age 73+/-12 years, range 34-99
      years. Seventy two subjects (27%) had heart failure as defined by left
      ventricular ejection fraction (LVEF) <or=40% and symptoms of heart failure (NYHA
      class II, III, or IV). Screening with NT-BNP gave a sensitivity of 73% and
      specificity of 72% for detecting heart failure in all patients [area under the
      curve (AUC) 0.76, P<0.001, 95% CI 0.69-0.83]. This increased in subjects with a
      DDD type pacemaker (sensitivity 80%, specificity 66%, AUC=0.8, CI 0.7-0.90) and
      reduced in subjects with a VVI type pacemaker (sensitivity 66%, specificity 61%,
      AUC 0.68 CI 0.57-0.78). CONCLUSION: Symptoms of heart failure are common in
      patients with pacemakers. Screening with NT-BNP is feasible and assists in the
      detection of important cardiac co-morbidity, particularly in patients with a DDD
      type pacemaker.

PMID- 16299021
TI  - Disease management programmes for older people with heart failure: crucial
      characteristics which improve post-discharge outcomes.
AB  - AIMS: Disease management programmes (DMPs) have evolved as an innovative clinical
      practice system to enhance the discharge outcomes of older people with heart
      failure. Yet, clinical trials which have examined their effectiveness have
      reported inconsistent findings. This may be explained by variations in the design
      of DMPs. The aim is to identify the characteristics of DMPs which are crucial to
      reducing hospital readmission and/or mortality of older people with heart
      failure. METHODS AND RESULTS: A systematic computerized search was conducted to
      identify randomized controlled trials of the last 10 years, which examined the
      effects of DMPs on hospital readmission and mortality of older people with heart
      failure. The identified DMPs were classified as effective and ineffective,
      according to statistically significant changes in discharge outcomes. Twenty-one
      trials were identified, 11 (52.4%) of which reported DMPs improving the discharge
      outcomes of older people with heart failure. The results indicate that an
      effective DMP should be multi-faceted and consists of an in-hospital phase of
      care, intensive patient education, self-care supportive strategy, optimization of
      medical regimen, and ongoing surveillance and management of clinical
      deterioration. Cardiac nurse and cardiologist should be actively involved and a
      flexible approach should be adopted to deliver the follow-up care. CONCLUSION:
      This study defines precisely the characteristics of the care team and the
      organization content and delivery method of the DMP which are crucial to enhance
      the discharge outcomes of older people with heart failure.

PMID- 16299023
TI  - Effectiveness of catheter ablation of atrial fibrillation.

PMID- 16299022
TI  - Impaired skin blood flow response to environmental heating in chronic heart
      failure.
AB  - AIMS: We examined the thermoregulatory response to heat exposure in patients with
      chronic heart failure. METHODS AND RESULTS: Skin blood flow (SkBF) was measured
      in HF subjects and matched controls. Cutaneous vascular conductance (CVC) was
      calculated from laser-Doppler SkBF and blood pressure. To assess the nitric oxide
      contribution to thermoregulatory responses, subcutaneous microdialysis membranes
      were placed beneath the laser-Doppler probes to infuse N(G)-nitro-l-arginine
      methyl ester (l-NAME), or Ringer's solution. Core (T(C)) and skin temperatures
      (five sites, T(Sk)) were continuously recorded. Subjects were studied during
      normothermia then at 38 degrees C, 50%RH within a climate chamber. T(C) and T(Sk)
      did not differ between HF and controls during normothermia and heating induced
      similar increases in both groups. During heating, CVC rose in both groups, but
      significantly less so in HF (HF 43.9+/-7.8 vs. controls 58.0+/-7.5% CVC(max),
      P<0.05). l-NAME attenuated SkBF responses in the control (58.0+/-7.5 vs. 34.6+/
      5.1% CVC(max), P<0.001) and HF subjects (43.9+/-7.8 vs. 27.0+/-2.2% CVC(max),
      P<0.005), with a larger effect evident in the controls (P<0.05). CONCLUSION: HF
      patients exhibit impaired thermoregulatory responses to heat exposure. Lower SkBF
      in HF, which defends blood pressure during heat exposure, also predisposes these
      subjects to heat intolerance.

PMID- 16299024
TI  - Comprehensive non-invasive pre-surgical magnetic resonance imaging in a patient
      with LEOPARD's syndrome cardiomyopathy.

PMID- 16299025
TI  - Life threatening intra-abdominal sepsis in patients on anti-TNF-alpha therapy.

PMID- 16299026
TI  - Polymorphisms in the T cell regulatory gene cytotoxic T lymphocyte antigen 4
      influence the rate of acute rejection after liver transplantation.
AB  - BACKGROUND: The cytotoxic T lymphocyte antigen 4 (CTLA-4) gene encodes for a
      membrane bound (mCTLA-4) and a soluble (sCTLA-4) isoform, which are both involved
      in regulation of T cell function. The CTLA-4 +49A/G single nucleotide
      polymorphism (SNP) influences expression of mCTLA-4; +6230G/A SNP affects the
      production of sCTLA-4. AIM: To examine whether these functional SNPs influence
      the rate of rejection after liver transplantation. PATIENTS AND METHODS: Liver
      graft recipients (n = 483) were genotyped for both SNPs, and haplotypes were
      reconstructed. Association with rejection was tested by the log rank test using
      the Kaplan-Meier method with time to the first acute rejection episode as
      outcome. Multiple analysis of SNPs together with demographic factors was
      performed by Cox regression. RESULTS: Three haplotypes were observed in the
      cohort: +49A/+6230A, +49A/+6230G, and +49G/+6230G. The +49A/+6230G haplotype was
      significantly and dose dependently associated with acute rejection (p = 0.01). Of
      the demographic factors tested, only underlying liver disease was significantly
      associated with rejection. Adjusted for underlying liver disease, each additional
      +49A/+6230G haplotype allele resulted in a significantly higher risk of acute
      rejection (risk ratio 1.34 (95% confidence interval 1.04-1.72); p = 0.02).
      Patients who lacked this haplotype had the lowest, carriers an intermediate, and
      homozygotes the highest risk of acute rejection. CONCLUSION: The CTLA-4
      +49A/+6230G haplotype, which encodes for normal mCTLA-4 expression but reduced
      sCTLA-4 production, is a co-dominant risk allele for acute rejection after
      clinical liver transplantation. This implies that even under immunosuppression,
      CTLA-4 is critically involved in the regulation of the human immune response to
      allogeneic grafts.

PMID- 16299027
TI  - Successful antibiotic treatment of Helicobacter pylori negative gastric mucosa
      associated lymphoid tissue lymphomas.
AB  - BACKGROUND AND AIMS: The role of antibiotic treatment in early stage gastric
      mucosa associated lymphoid tissue (MALT) lymphoma not associated with
      Helicobacter pylori infection has not been investigated. PATIENTS AND METHODS:
      Six patients with localised gastric MALT lymphoma underwent antibiotic treatment
      with clarithromycin, metronidazole, and pantoprazole. Staging, including
      endosonography plus gastroscopy, computed tomography of the thorax and abdomen,
      colonoscopy, magnetic resonance imaging of the salivary glands, and bone marrow
      biopsy were performed to rule out distant spread of the disease. In addition,
      MALT specific genetic changes, including reverse transcriptase-polymerase chain
      reaction for t(11;18)(q21;q21), were tested in all patients. H pylori infection
      was ruled out by histology, urease breath test, serology, and stool antigen
      testing. RESULTS: All six patients had MALT lymphoma restricted to the stomach,
      and no evidence of infection with H pylori was found. Only one patient tested
      positive for t(11;18)(q21;q21) while the remaining five displayed no genetic
      aberrations. Following antibiotic treatment, endoscopic controls were performed
      every three months. Five patients responded with lymphoma regression between
      three and nine months following antibiotic treatment (one partial remission and
      four complete responses). One patient had stable disease for 12 months and was
      then referred for chemotherapy. CONCLUSIONS: Patients with early stage gastric
      MALT lymphoma negative for H pylori might still benefit from antibiotic treatment
      as the sole treatment modality.

PMID- 16299028
TI  - Immune control of food intake: enteroendocrine cells are regulated by CD4+ T
      lymphocytes during small intestinal inflammation.
AB  - BACKGROUND AND AIMS: Gastrointestinal inflammation reduces food intake but the
      biological mechanisms explaining suppressed feeding during inflammation are
      unknown. We have used a model of upper gut infection (Trichinella spiralis in the
      mouse) to study the effect of inflammation on food intake, and explored the role
      of a key enteroendocrine cell (EEC) in the regulation of feeding by the immune
      response. METHODS: Food intake of NIH mice infected with the intestinal nematode
      Trichinella spiralis was measured. Duodenal cholecystokinin (CCK) cells were
      counted. Plasma CCK was measured. Infected mice were treated with a specific CCK1
      receptor antagonist, and food intake reassessed. The influence of the immune
      response on food intake and CCK was mechanistically examined by treating mice
      with CD4 or mast cell neutralising antibodies. The role of the T helper 2
      response was further explored in mice genetically deficient for interleukin (IL)
      4, IL-13, or IL-4Ralpha (receptor alpha subunit). RESULTS: Food intake of
      infected mice was significantly reduced at the temporal peak of intestinal
      inflammation. CCK expressing EEC were upregulated in infected mice, and plasma
      CCK levels were increased. A CCK1 receptor antagonist restored the food intake of
      infected mice to a significant degree. Furthermore, suppression of food intake
      was completely abolished in the absence of CD4+ T lymphocytes or IL-4Ralpha.
      CONCLUSIONS: The data show for the first time that intestinal inflammation
      results in reduced food intake due to upregulation of CCK. Moreover, following
      infection, food intake and CCK expressing cells are under the specific control of
      CD4+ T-cells, via release of IL-4 and IL-13.

PMID- 16299029
TI  - Physical activity, insulin-like growth factor 1, insulin-like growth factor
      binding protein 3, and survival from colorectal cancer.
AB  - BACKGROUND: Recent reports have shown that physical activity improves the outcome
      of patients with colorectal cancer as well as breast and prostate cancer.
      However, the mechanisms whereby physical activity reduces cancer mortality are
      not well established. METHODS: Incident cases of colorectal cancer were
      identified among participants of the Melbourne Collaborative Cohort Study, a
      prospective cohort study of 41,528 Australians recruited from 1990 to 1994.
      Information on tumour site and stage, treatments given, recurrences, and deaths
      were obtained from systematic review of the medical records. Baseline assessments
      of physical activity and body size were made, and cases with available plasma had
      pre-diagnosis insulin-like growth factor 1 (IGF-1) and insulin-like growth factor
      binding protein 3 (IGFBP-3) levels measured. We assessed associations between
      these hormones and colorectal cancer specific deaths with respect to physical
      activity. RESULTS: A total of 526 cases of colorectal cancer were identified, of
      which 443 had IGF-1/IGFBP-3 levels measured. Median follow up among survivors was
      5.6 years. For the physically active, increasing IGFBP-3 by 26.2 nmol/l was
      associated with a 48% reduction in colorectal cancer specific deaths (adjusted
      hazard ratio (HR) 0.52 (0.33-0.83); p = 0.006). No association was seen for IGF-1
      (adjusted HR 0.90 (0.55-1.45); p = 0.65). For the physically inactive, neither
      IGF-1 nor IGFBP-3 was associated with disease specific survival. CONCLUSIONS:
      This study supports the hypothesis that the beneficial effects of physical
      activity in reducing colorectal cancer mortality may occur through interactions
      with the insulin-like growth factor axis and in particular IGFBP-3.

PMID- 16299030
TI  - Gli1, downregulated in colorectal cancers, inhibits proliferation of colon cancer
      cells involving Wnt signalling activation.
AB  - BACKGROUND: Early events in the progression of 90% of sporadic colorectal cancers
      depend on constitutive activation of Wnt signalling. Recent data also indicate a
      close association between the Hedgehog (Hh) and Wnt pathways in colonic
      epithelial cell differentiation. AIMS: To investigate whether expression of Gli1,
      a transactivator of Hh signalling, can suppress Wnt signalling and inhibit
      proliferation of human colorectal cancer cells. METHODS: Gli1 and nuclear beta
      catenin expression were examined in a series of 40 human colorectal cancers by
      immunohistochemistry. We quantified Gli1 and nuclear beta-catenin staining as
      markers of Hh and Wnt pathway activation, respectively. Two human colon cancer
      cell lines, SW480 and HCT116, with mutations in APC and beta-catenin,
      respectively, were used. The effects of Gli1 overexpression on Wnt
      transcriptional activity, beta-catenin subcellular distribution, and
      proliferation in these cells were analysed. RESULTS: Nuclear accumulation of beta
      catenin and the Gli1 staining level were inversely associated in the 40 human
      colorectal cancers. Wnt transcriptional activity was reduced in Gli1 transfected
      cells. These effects were observed even in Gli1 transfected cells cotransfected
      with mutated beta-catenin. Furthermore, nuclear accumulation of beta-catenin was
      diminished compared with that in empty vector transfected cells, and
      downregulated transcription of c-Myc was observed in Gli1 transfected cells.
      Proliferation of Gli1 transfected cells was also significantly suppressed
      compared with that in empty vector transfected cells. CONCLUSIONS: Our data
      suggest that Gli1 plays an inhibitory role in the development of colorectal
      cancer involving Wnt signalling, even in cases with the stabilising mutation of
      beta-catenin.

PMID- 16299031
TI  - Mu opioid receptor expression is increased in inflammatory bowel diseases:
      implications for homeostatic intestinal inflammation.
AB  - BACKGROUND AND AIMS: Recent studies with mu opioid receptor (MOR) deficient mice
      support a physiological anti-inflammatory effect of MOR at the colon interface.
      To better understand the potential pharmacological effect of certain opiates in
      inflammatory bowel diseases (IBD), we (1) evaluated the regulation in vivo and in
      vitro of human MOR expression by inflammation; and (2) tested the potential anti
      inflammatory function of a specific opiate (DALDA) in inflamed and resting human
      mucosa. PATIENTS AND METHODS: Expression of MOR mRNA and protein was evaluated in
      healthy and inflamed small bowel and colonic tissues, isolated peripheral blood
      mononuclear cells and purified monocytes, and CD4+ and CD8+ T cells from healthy
      donors and IBD patients. The effect of cytokines and nuclear factor kappaB
      (NFkappaB) activation on MOR expression in lymphocyte T and monocytic human cell
      lines was assessed. Finally, DALDA induced anti-inflammatory effect was
      investigated in mucosal explants from controls and IBD patients. RESULTS: MOR was
      expressed in ileal and colonic enteric neurones as well as in immunocytes such as
      myeloid cells and CD4+ and CD8+ T cells. Overexpressed in active IBD mucosa, MOR
      was significantly enhanced by cytokines and repressed by NFkappaB inhibitor in
      myeloid and lymphocytic cell lines. Furthermore, ex vivo DALDA treatment dampened
      tumour necrosis factor alpha mRNA expression in the colon of active IBD patients.
      CONCLUSIONS: Given the increased expression of MOR and the ex vivo beneficial
      effect of DALDA in active IBD, natural and/or synthetic opioid agonists could
      help to prevent overt pathological intestinal inflammation.

PMID- 16299032
TI  - Four year follow up of fatigue in a geographically defined primary biliary
      cirrhosis patient cohort.
AB  - BACKGROUND AND AIMS: Fatigue is the commonest symptom described by patients in
      most populations with the autoimmune liver disease primary biliary cirrhosis
      (PBC), and appears to be unrelated to liver disease severity. At present, it is
      unclear how the fatigue experienced by patients (only characterised to date in
      cross sectional studies) evolves over time. In this study, we set out to address
      how fatigue had changed over four years of follow up in a geographically defined
      cohort of PBC patients who participated in an earlier cross sectional study of
      fatigue impact. METHODS: Participants in the original 2000 study who were still
      alive in 2004 were asked to complete the same fatigue assessment tool (fatigue
      impact score, FIS). In those who had died between 2000 and 2004, medical notes,
      death certificates, and primary care records were reviewed. RESULTS: A total of
      108 of the original cohort of 136 patients were alive at the time of the follow
      up study, 99 of whom (92%) participated in the follow up study. With the
      exception of four patients who underwent transplantation between 2000 and 2004,
      all of whom showed significant improvement in fatigue severity as assessed by
      FIS, fatigue severity was unchanged over four years of follow up. Among the 28
      patients who died during the follow up period, survival was significantly lower
      in patients who were fatigued at the 2000 baseline (FIS above the median for the
      whole PBC population (40/160); log rank test, p = 0.006 v non-fatigued patients
      at baseline). Increased fatigue severity was independently associated with
      decreased survival on multivariate analysis. Fatigued PBC subjects were
      significantly more likely to have suffered a cardiac death than non-fatigued
      patients. CONCLUSIONS: The fatigue phenotype appears to be highly stable in PBC.
      The presence of fatigue in PBC is independently associated with a significantly
      increased risk of death in general, and cardiac death in particular. Factors
      underpinning fatigue in PBC, and the mechanisms whereby fatigue is associated
      with increased mortality, warrant further study.

PMID- 16299033
TI  - Apolipoprotein epsilon3 allele is associated with persistent hepatitis C virus
      infection.
AB  - BACKGROUND: Host genetic factors may significantly influence the ability to clear
      hepatitis C virus (HCV) following infection. HCV is associated with very low
      density lipoproteins (VLDL) and low density lipoproteins (LDL) in the host's
      circulation. Apolipoprotein E (APOE) is found in VLDL and binds to potential
      receptors involved in HCV entry into cells, the LDL receptor, and the scavenger
      receptor protein SR-B1. The APOE gene is polymorphic with three alleles coding
      for three isoforms: Apo-epsilon2, Apo-epsilon3, and Apo-epsilon4. The aim of this
      study was to assess if these functional polymorphisms determine disease outcome
      in HCV infected individuals. METHODS: The APOE genotype was determined in 420
      Northern European patients with evidence of exposure to HCV. Genotype and allele
      distribution were compared with those of 288 healthy controls and progression of
      liver disease and viral clearance were analysed according to APOE allele status.
      RESULTS: The APOE*E2 and APOE*E4 alleles were both associated with a reduced
      likelihood of chronic infection (odds ratio (OR) 0.39 (95% confidence interval
      (CI) 0.211-0.728), p = 0.003; and OR 0.6 (95% CI 0.38-0.96), p = 0.032) and there
      was a notable absence of the E2E2 genotype in the HCV antibody positive group
      compared with the control population (p = 0.0067). Overall the genotypes carrying
      the E2 allele (E2,E3 and E2,E4) were associated with the equivalent of a 3-5-fold
      reduction in the risk of chronic HCV infection (genotype relative risk 0.36 and
      0.20, respectively). CONCLUSION: This study indicates that functional APOE gene
      polymorphisms may be a determinant of outcome in HCV infection. We hypothesise
      that the E2 allele may protect against viral persistence via defective binding of
      HCV lipoviral particles to the cellular receptors involved in entry of these
      infectious particles.

PMID- 16299034
TI  - Phenotypic changes in colonocytes following acute stress or activation of mast
      cells in mice: implications for delayed epithelial barrier dysfunction.
AB  - BACKGROUND AND AIMS: Stressful life events are known to modulate the development
      or relapse of disease in both inflammatory bowel disease and irritable bowel
      disease patients but underlying mechanisms remain unclear. Stress is known to
      effect mast cells, interferon gamma (IFN-gamma), and myosin light chain
      phosphorylation to trigger colonic epithelial barrier dysfunction. The aim of
      this study was to investigate whether acute stress induced or chemical mast cell
      activation impaired expression and function of epithelial tight junctions, and
      altered colonocyte differentiation in mice. METHODS: Colonic paracellular
      permeability was assessed as the in vivo lumen to blood ratio of 51Cr-EDTA in
      different groups of mice (controls, stressed, mast cell degranulator BrX-537A
      treated), pretreated or not with the mast cell stabiliser doxantrazole.
      Involvement of mast cells and IFN-gamma was evaluated in wild-type and IFN-gamma
      deficient mice. Tight junction alteration was assessed by histology, transmission
      electron microscopy, and real time reverse transcription-polymerase chain
      reaction. Colonocyte differentiation was determined by protein kinase C zeta
      (PKCzeta) immunofluorescence and western blotting, and alkaline phosphatase
      activity assay. RESULTS: Acute stress induced a three day delayed increase in
      colonic paracellular permeability which involved mast cell degranulation and
      overproduction of IFN-gamma. The colonic epithelial barrier was morphologically
      altered and expression of mRNA encoding tight junction proteins ZO-2 and occludin
      was decreased. Moreover, three days after acute stress, colonocyte
      differentiation was reduced, as shown by decreased expression of both PKCzeta
      isotype and alkaline phosphatase. CONCLUSION: These data highlight new mechanisms
      whereby an acute stress acts on the gastrointestinal tract by inducing
      alterations in colonocyte differentiation and decreased expression of mRNA
      encoding tight junction proteins. Thus phenotypic changes in colonocytes could
      pave the way for stress related intestinal disorders.

PMID- 16299035
TI  - Inducible nitric oxide synthase activity contributes to the regulation of
      peripheral vascular tone in patients with cirrhosis and ascites.
AB  - BACKGROUND: Overexpression of inducible nitric oxide synthase (iNOS) and
      increased nitric oxide generation may be associated with the hyperdynamic
      circulation of patients with cirrhosis. We have, for the first time, used the
      highly selective iNOS inhibitor, 1400W, to determine whether iNOS activity
      contributes to the regulation of vascular tone in patients with cirrhosis and
      ascites. METHODS: Bilateral forearm blood flow was measured using strain gauge
      plethysmography in eight patients with cirrhosis and ascites, and eight matched
      healthy volunteers during intrabrachial infusion of 1400W (0.1-1 micromol/min),
      N(G)-monomethyl-L-arginine (L-NMMA, a non-selective NOS inhibitor; 2-8 micromol),
      and norepinephrine (a control vasoconstrictor; 60-480 pmol/min). RESULTS: In
      patients with cirrhosis, 1400W, L-NMMA, and norepinephrine caused dose dependent
      reductions in forearm blood flow: peak reductions of 11 (5)%, 37 (4)%, and 48
      (5)%, respectively (p < 0.05 for all). In contrast, 1400W had no effect on blood
      flow (+4 (8)%; NS) in healthy controls despite similar reductions in blood flow
      with L-NMMA and norepinephrine (39 (5)% and 49 (5)%, respectively; p < 0.05 for
      both). CONCLUSIONS: We have, for the first time, demonstrated that 1400W causes
      peripheral vasoconstriction in patients with cirrhosis but not healthy matched
      controls. This suggests that iNOS contributes to the regulation of peripheral
      vascular tone in patients with cirrhosis and ascites, and may contribute towards
      the hyperdynamic circulation associated with this condition.

PMID- 16299036
TI  - Mismatch repair status in the prediction of benefit from adjuvant fluorouracil
      chemotherapy in colorectal cancer.
AB  - AIM: Some retrospective studies have shown a lack of benefit of 5-fluorouracil (5
      FU) adjuvant chemotherapy in patients with mismatch repair (MMR) deficient
      colorectal cancer. Our aim was to assess if this molecular marker can predict
      benefit from 5-FU adjuvant chemotherapy. A second objective was to determine if
      MMR status influences short term survival. METHODS: We included 754 patients with
      a median follow up of 728.5 days (range 1-1097). A total of 260 patients with
      stage II or III tumours received 5-FU adjuvant chemotherapy, according to
      standard clinical criteria and irrespective of their MMR status. A tumour was
      considered MMR deficient when either BAT-26 showed instability or there was loss
      of MLH1 or MSH2 protein expression. RESULTS: At the end of the follow up period,
      206 patients died and 120 presented with tumour recurrence. Sixty six (8.8%)
      patients had MMR deficient tumours. There were no significant differences in
      overall survival (MMR competent 72.1%; MMR deficient 78.8%; p = 0.3) or disease
      free survival (MMR competent 61.3%; MMR deficient 72.3%; p = 0.08). In patients
      with stage II and III tumours, benefit from 5-FU adjuvant chemotherapy was
      restricted to patients with MMR competent tumours (overall survival: chemotherapy
      87.1%; non-chemotherapy 73.5%; log rank, p = 0.00001). Patients with MMR
      deficient tumours did not benefit from adjuvant chemotherapy (overall survival:
      chemotherapy 89.5%; non-chemotherapy 82.4%; log rank, p = 0.4). CONCLUSIONS:
      Benefit from 5-FU adjuvant chemotherapy depends on the MMR status of tumours in
      patients with colorectal cancer. 5-FU adjuvant chemotherapy improves survival in
      patients with MMR competent tumours but this benefit from chemotherapy cannot be
      extended to patients with MMR deficient tumours.

PMID- 16299038
TI  - Elevated anal squamous cell carcinoma risk associated with benign inflammatory
      anal lesions.
AB  - BACKGROUND: The association between benign anal lesions and anal cancer is still
      unclear. Few data from large cohort studies are available. METHODS: We conducted
      a register based retrospective cohort study including 45,186 patients
      hospitalised for inflammatory anal lesions (anal fissures, fistulas, and perianal
      abscesses) as well as 79,808 haemorrhoid patients, from 1965 to 2002. Multiple
      record linkages identified all incident anal (squamous cell carcinoma only) and
      colorectal cancers through to 2002. Relative risk was estimated by standardised
      incidence ratio (SIR), the ratio of observed number of cases divided by that
      expected in the age, sex, and calendar year-matched general Swedish population.
      RESULTS: There was a distinct incidence peak in the first three years of follow
      up among patients with inflammatory lesions. SIR then levelled off at around 3
      and remained at this level throughout follow up (SIR during years 3-37 of follow
      up was 3.3 (95% confidence interval 1.8-5.7)). A similar initial incidence peak
      was observed among haemorrhoid patients but was confined to the first year; SIR
      was 2.8 in the second year, and then it decreased further and was close to unity
      in the following years (SIR during years 3-37 was 1.3 (95% confidence interval
      0.7-2.1)). Among inflammatory lesion and haemorrhoid patients, a significantly
      increased risk of colorectal cancer was observed only in the first year after
      hospitalisation. CONCLUSIONS: Inflammatory benign anal lesions are associated
      with a significantly increased long term risk of anal cancer. In contrast,
      haemorrhoids appear not to be a risk factor for this malignancy.

PMID- 16299037
TI  - Propionibacterium freudenreichii component 1.4-dihydroxy-2-naphthoic acid (DHNA)
      attenuates dextran sodium sulphate induced colitis by modulation of bacterial
      flora and lymphocyte homing.
AB  - BACKGROUND AND AIMS: 1.4-Dihydroxy-2-naphthoic acid (DHNA), a bifidogenic growth
      stimulator from Propionibacterium freudenreichii, is thought to have a beneficial
      effect as a prebiotic; however, its in vivo effect on intestinal inflammation
      remains unknown. The aim of this study was to determine whether oral
      administration of DHNA can ameliorate dextran sodium sulphate (DSS) induced
      colitis and to determine the possible underlying mechanisms. METHOD: Colitis was
      induced in mice by treatment with 2.0% DSS for seven days. DHNA (0.6 or 2.0
      mg/kg) was given in drinking water prior to (preventive study) or after
      (therapeutic study) DSS administration. Colonic damage was histologically scored,
      and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) expression and beta7
      positive cell infiltration were determined by immunohistochemistry. mRNA levels
      of proinflammatory cytokines (interleukin (IL)-1beta, IL-6 and tumour necrosis
      factor alpha (TNF-alpha)) were determined by quantitative real time polymerase
      chain reaction. In addition, bacterial flora in the caecum, concentrations of
      short chain acids, and luminal pH were examined. RESULTS: DHNA improved survival
      rate and histological damage score in mice administered DSS in both the
      preventive and therapeutic studies. DHNA significantly attenuated the enhanced
      expression of MAdCAM-1, the increased beta7 positive cell number, and the
      increased mRNA levels of IL-1beta, IL-6, and TNF-alpha in DSS treated colon. In
      addition, the decreased number of Lactobacillus and Enterobacteriaceae induced by
      DSS was recovered by DHNA. Preventive effects on decrease in butyrate
      concentration and decrease in pH level in mice administered DSS were also
      observed in the DHNA preventive study. CONCLUSION: DHNA, a novel type of
      prebiotic, attenuates colonic inflammation not only by balancing intestinal
      bacterial flora but also by suppressing lymphocyte infiltration through reduction
      of MAdCAM-1.

PMID- 16299039
TI  - Non-response to antiviral therapy is associated with obesity and increased
      hepatic expression of suppressor of cytokine signalling 3 (SOCS-3) in patients
      with chronic hepatitis C, viral genotype 1.
AB  - BACKGROUND: Interferon alpha (IFN-alpha) activated cellular signalling is
      negatively regulated by inhibitory factors, including the suppressor of cytokine
      signalling (SOCS) family. The effects of host factors such as obesity on hepatic
      expression of these inhibitory factors in subjects with chronic hepatitis C virus
      (HCV) are unknown. OBJECTIVES: To assess the independent effects of obesity,
      insulin resistance, and steatosis on response to IFN-alpha therapy and to
      determine hepatic expression of factors inhibiting IFN-alpha signalling in obese
      and non-obese subjects with chronic HCV. METHODS: A total of 145 subjects were
      analysed to determine host factors associated with non-response to antiviral
      therapy. Treatment comprised IFN-alpha or peginterferon alpha, either alone or in
      combination with ribavirin. In a separate cohort of 73 patients, real time
      polymerase chain reaction was performed to analyse hepatic mRNA expression.
      Immunohistochemistry for SOCS-3 was performed on liver biopsy samples from 38
      patients with viral genotype 1 who had received antiviral treatment. RESULTS: Non
      response (NR) to treatment occurred in 55% of patients with HCV genotypes 1 or 4
      and 22% with genotypes 2 or 3. Factors independently associated with NR were
      viral genotype 1/4 (p < 0.001), cirrhosis on pretreatment biopsy (p = 0.025), and
      body mass index > or = 30 kg/m2 (p = 0.010). Obese subjects with viral genotype 1
      had increased hepatic mRNA expression of phosphoenolpyruvate carboxy kinase (p =
      0.01) and SOCS-3 (p = 0.047), in comparison with lean subjects. Following
      multivariate analysis, SOCS-3 mRNA expression remained independently associated
      with obesity (p = 0.023). SOCS-3 immunoreactivity was significantly increased in
      obesity (p = 0.013) and in non-responders compared with responders (p = 0.014).
      CONCLUSIONS: In patients with chronic HCV viral genotype 1, increased expression
      of factors that inhibit interferon signalling may be one mechanism by which
      obesity reduces the biological response to IFN-alpha.

PMID- 16299040
TI  - Induction of a fibrogenic response in mouse colon by overexpression of monocyte
      chemoattractant protein 1.
AB  - BACKGROUND AND AIMS: Monocyte chemoattractant protein 1 (MCP-1) is increased
      transmurally in inflammatory bowel disease (IBD). Although MCP-1 is considered to
      play an important role in fibrotic disease in other organs, the role of MCP-1 in
      gut fibrosis is unknown. We investigated the fibrotic potential of MCP-1 in the
      gut by overexpressing this chemokine in the mouse colorectal wall. METHODS:
      Intramural gene transfer by direct injection of adenovector into the mouse rectal
      wall was established. C57BL/6 and Rag2(-/-) (B and T cell deficient) mice
      received 2.5 x 10(9) plaque forming units of an adenovector encoding murine MCP-1
      (AdMCP-1) or control virus (AdDL70) via intramural injection. Mice were killed at
      various time points and tissues were obtained for histopathological and
      biochemical analysis. RESULTS: AdMCP-1 significantly increased collagen
      production in the colorectum and this was associated with significant elevation
      of transforming growth factor beta (TGF-beta) and tissue inhibitor of
      metalloproteinase (TIMP-1) protein. Transmural collagen deposition was observed
      after AdMCP-1 administration, and was accompanied by CD3+ T cells, F4/80+
      macrophages, and vimentin+ cell infiltrates. Collagen was differentially
      distributed, with type I deposited in the muscularis mucosa and muscularis
      propria and type III in the submucosa and myenteric plexus. AdMCP-1 failed to
      induce collagen overproduction in immunodeficient Rag2(-/-) mice. CONCLUSION:
      These findings suggest that MCP-1 can induce fibrosis in the gut and that this
      process involves interaction between T cells and vimentin positive
      fibroblasts/myofibroblasts, as well as the subsequent upregulation of TGF-beta
      and TIMP-1 production. This model provides a basis for considering MCP-1 in the
      pathogenesis of strictures in IBD.

PMID- 16299041
TI  - Antagonists and non-toxic variants of the dominant wheat gliadin T cell epitope
      in coeliac disease.
AB  - BACKGROUND: Coeliac disease (CD) is due to an inappropriate T cell mediated
      response to specific gluten peptides. Measured by interferon gamma (IFN-gamma)
      ELISPOT, about half of the gliadin specific T cells induced with in vivo wheat
      gluten exposure in HLA-DQ2+ CD are specific for an alpha/beta-gliadin peptide
      (p57-73 QE65; QLQPFPQPELPYPQPQS) that includes two overlapping T cell epitopes
      (PFPQPELPY and PQPELPYPQ). AIM: To define minimally substituted variants of p57
      73 QE65 universally devoid of IFN-gamma stimulatory capacity but capable of
      antagonising IFN-gamma secretion from polyclonal T cells specific for p57-73
      QE65. METHODS: Peripheral blood mononuclear cells collected from 75 HLA-DQ2+ CD
      patients after in vivo gluten challenge were used in overnight ELISPOT assays to
      screen 218 single or double substituted variants of p57-73 QE65 for cytokine
      stimulatory and antagonist activity. RESULTS: The region p60-71 (PFPQPELPYPQP)
      and especially p64-67 (PELP) was sensitive to substitution. Twelve substitutions
      in p64-67 stimulated no IFN-gamma ELISPOT response. Among 131 partial agonists
      identified, 45 produced statistically significant inhibition of IFN-gamma ELISPOT
      responses when cocultured in fivefold excess with p57-73 QE65 (n = 10). Four
      substituted variants of p57-73 QE65 were inactive by IFN-gamma ELISPOT but
      consistently antagonised IFN-gamma ELISPOT responses to p57-73 QE65, and also
      retained interleukin 10 stimulatory capacity similar to p57-73 QE65. CONCLUSIONS:
      Altered peptide ligands of p57-73 QE65, identified using polyclonal T cells from
      multiple HLA-DQ2+ CD donors, have properties in vitro that suggest that a single
      substitution to certain alpha/beta-gliadins could abolish their capacity to
      stimulate IFN-gamma from CD4 T cells and also have anti-inflammatory or
      protective effects in HLA-DQ2+ CD.

PMID- 16299043
TI  - Tracheo-innominate artery fistula after percutaneous tracheostomy: three case
      reports and a clinical review.
AB  - Tracheo-innominate artery fistula (TIF) is an uncommon yet life threatening
      complication after a tracheostomy. Rates of 0.1-1% after surgical tracheostomy
      have been reported, with a peak incidence at 7-14 days post procedure. It is
      usually fatal unless treatment is instituted immediately. Initial case reports of
      TIF resulted from surgically performed tracheostomies. We present three
      fatalities attributable to TIF, confirmed by histopathology, after percutaneous
      dilatational tracheostomy (PDT). The use of PDT has resulted in tracheostomies
      being performed by specialists from different backgrounds and the incidence of
      this complication may be increasing. Pressure necrosis from high cuff pressure,
      mucosal trauma from malpositioned cannula tip, low tracheal incision,
      radiotherapy and prolonged intubation are all implicated in TIF formation.
      Massive haemorrhage occurring 3 days to 6 weeks after tracheostomy is a result of
      TIF until proven otherwise. We present a simple algorithm for management of this
      situation. The manoeuvres outlined will control bleeding in more than 80% of
      patients by a direct tamponade effect. Surgical stasis is obtained by debriding
      the innominate artery proximally, then transecting and closing the lumen.
      Neurological sequelae are few. Post-mortem diagnosis of TIF may be difficult, but
      specific pathology request should be made to assess innominate artery
      abnormalities.

PMID- 16299042
TI  - Selective expression of histamine receptors H1R, H2R, and H4R, but not H3R, in
      the human intestinal tract.
AB  - BACKGROUND AND AIMS: Histamine is known as a regulator of gastrointestinal
      functions, such as gastric acid production, intestinal motility, and mucosal ion
      secretion. Most of this knowledge has been obtained from animal studies. In
      contrast, in humans, expression and distribution of histamine receptors (HR)
      within the human gastrointestinal tract are unclear. METHODS: We analysed HR
      expression in human gastrointestinal tissue specimens by quantitative reverse
      transcription-polymerase chain reaction and immunostaining. RESULTS: We found
      that H1R, H2R, and H4R mRNA were expressed throughout the gastrointestinal tract,
      while H3R mRNA was absent. No significant differences in the distribution of HR
      were found between different anatomical sites (duodenum, ileum, colon, sigma, and
      rectum). Immunostaining of neurones and nerve fibres revealed that H3R was absent
      in the human enteric nervous system; however, H1R and H2R were found on ganglion
      cells of the myenteric plexus. Epithelial cells also expressed H1R, H2R and, to
      some extent, H4R. Intestinal fibroblasts exclusively expressed H1R while the
      muscular layers of human intestine stained positive for both H1R and H2R. Immune
      cells expressed mRNA and protein for H1R, H2R, and low levels of H4R. Analysis of
      endoscopic biopsies from patients with food allergy and irritable bowel syndrome
      revealed significantly elevated H1R and H2R mRNA levels compared with controls.
      CONCLUSIONS: We have demonstrated that H1R, H2R and, to some extent, H4R, are
      expressed in the human gastrointestinal tract, while H3R is absent, and we found
      that HR expression was altered in patients with gastrointestinal diseases.

PMID- 16299044
TI  - A case of post-reperfusion syndrome following surgery for liver trauma.
AB  - We report the case of a young trauma patient who needed tight perihepatic
      surgical packing to control bleeding from a ruptured liver. He developed severe
      cardiovascular and respiratory decompensation on removal of the surgical packs as
      a result of the post-reperfusion syndrome. He underwent a total hepatectomy and,
      35 h later, orthotopic liver transplantation. The pathophysiology of post
      reperfusion syndrome is discussed, and its importance to anaesthetists in the non
      transplant setting is emphasized.

PMID- 16299045
TI  - Interhospital transportation of patients with severe lung failure on pumpless
      extracorporeal lung assist.
AB  - BACKGROUND: To describe the use of pumpless extracorporeal interventional lung
      assist (iLA) for transportation of patients with severe life-threatening acute
      lung failure from tertiary hospitals to a specialized centre. METHODS:
      Retrospective analysis in eight patients with severe lung failure requiring
      interhospital transport, in whom implementation of an iLA system at a tertiary
      hospital for air/ground transportation was performed. RESULTS: After
      implementation of iLA, a rapid increase in CO2-elimination (Pa(CO2) before iLA:
      8.92+/-2.9 kPa, immediately after implementation: 5.06+/-0.93 kPa, 24 h after
      implementation: 4.53+/-1.20 kPa [mean+/-SD], P<0.05) was observed and a
      significant improvement in oxygenation (Pa(O2) before iLA: 6.66+/-2.26 kPa,
      immediately after implementation: 10.39+/-3.33 kPa, 24 h after implementation:
      10.25+/-5.46 kPa, P<0.05) was noted. During transport, no severe complications
      occurred. Four patients died during further treatment due to multiple trauma or
      multiple organ failure. CONCLUSIONS: Due to ease of handling, high effectiveness
      and relatively low costs, iLA seems to be a useful system for treatment and
      transportation of patients with severe acute lung injury or ARDS suffering from
      life-threatening hypoxia and/or hypercapnia.

PMID- 16299046
TI  - Normalization of acceleromyographic train-of-four ratio by baseline value for
      detecting residual neuromuscular block.
AB  - BACKGROUND: This study was designed to recognize the importance of normalizing
      postoperative acceleromyographic train-of-four (TOF) ratio by the baseline TOF
      value obtained before neuromuscular block for ensuring adequate recovery of
      neuromuscular function. METHODS: In 120 patients, TOF responses of the adductor
      pollicis to the ulnar nerve stimulation were monitored by acceleromyography (AMG)
      during anaesthesia using propofol, fentanyl and nitrous oxide. Control TOF
      stimuli were administered for 30 min. A TOF ratio measured at the end of control
      stimulation was regarded as a baseline value. Neuromuscular block was induced
      with vecuronium 0.1 mg kg(-1) and was allowed to recover spontaneously. Duration
      to a TOF ratio of 0.9 as calculated by AMG (DUR-raw 0.9) was compared with that
      of 0.9 as corrected by the baseline TOF ratio (i.e. 0.9 x baseline TOF ratio; DUR
      real 0.9). RESULTS: Baseline TOF ratios ranged from 0.95 to 1.47. The average TOF
      ratios observed every 5 min were constant throughout control stimulation from at
      time zero mean (SD) [range]; 1.11 (0.09) [0.94-1.42] to at 30 min 1.13 (0.11)
      [0.95-1.47]. The DUR-real 0.9 was 91.0 (18.0) [51.3-131.0] min and was
      significantly longer than the DUR-raw 0.9 (81.2 (16.3) [41.3-123.0] min).
      CONCLUSIONS: Baseline TOF ratios measured by AMG are usually more than 1.0 and
      vary widely among patients. Therefore a TOF ratio of 0.9 displayed
      postoperatively on AMG does not always represent adequate recovery of
      neuromuscular function and should be normalized by baseline value to reliably
      detect residual paralysis.

PMID- 16299047
TI  - Local anaesthetics inhibit signalling of human NMDA receptors recombinantly
      expressed in Xenopus laevis oocytes: role of protein kinase C.
AB  - BACKGROUND: N-methyl-D-aspartate (NMDA)-receptor activation contributes to
      postoperative hyperalgesia. Studies in volunteers have shown that intravenous
      local anaesthetics (LAs) prevent the development of hyperalgesic pain states. One
      potential explanation for this beneficial effect is the inhibition of NMDA
      receptor activation. Therefore, we studied the effects of LA on NMDA receptor
      function. METHODS: The human NR1A/NR2A NMDA receptor was expressed recombinantly
      in Xenopus laevis oocytes. Peak currents were measured by voltage clamp in Mg-
      and Ca2+-free, Ba2+-containing Tyrode's solution. Holding potential was -70 mV.
      Oocytes were stimulated with glutamate/glycine (at EC50) with or without 10 min
      prior incubation in bupivacaine, levobupivacaine, S-(-)-ropivacaine, or lidocaine
      (all at 10(-9)-10(-4) M), procaine (10(-4) M), R-(+)-ropivacaine (10(-4) M),
      QX314 (permanently charged, 5 x 10(-4) M) extracellularly or intracellularly or
      benzocaine (permanently uncharged, 5 x 10(-3) M). We also determined the effect
      of the protein kinase C (PKC) inhibitors chelerythrine (5 x 10(-5) M), calphostin
      C (3 x 10(-6) M) and Ro 31-8220 (10(-7) M), and the effect of PKC activation with
      phorbolester (10(-6) M). RESULTS: Non-injected oocytes were unresponsive to
      agonist application, but oocytes expressing NMDA receptors responded with inward
      currents (1.1+/-0.08 microA). All LA concentration-dependently inhibited agonist
      responses. The inhibition was reversible and stereoselective. Intracellular QX314
      reduced responses to 59% of control, but extracellular QX314 was without effect.
      Benzocaine reduced responses to 33% of control. PKC inhibitors had no additional
      inhibitory effect beyond that of bupivacaine. The effect of PKC activation was
      abolished in the presence of bupivacaine. CONCLUSION: All LA tested inhibited the
      activation of human NMDA receptors in a concentration dependent fashion. This
      effect may contribute to reduced hyperalgesia and opiate tolerance observed after
      systemic administration of LA. The effect is independent of the charge of LA;
      site of action is intracellular. The mechanism of action may be mediated by
      inhibition of PKC.

PMID- 16299048
TI  - Clinical analysis by microchip capillary electrophoresis.
AB  - Clinical analysis often requires rapid, automated, and high-throughput analytical
      systems. Microchip capillary electrophoresis (CE) has the potential to achieve
      very rapid analysis (typically seconds), easy integration of multiple analytical
      steps, and parallel operation. Although it is currently still in an early stage
      of development, there are already many reports in the literature describing the
      applications of microchip CE in clinical analysis. At the same time, more fully
      automated and higher throughput commercial instruments for microchip CE are
      becoming available and are expected to further enhance the development of
      applications of microchip CE in routine clinical testing. To put into perspective
      its potential, we briefly compare microchip CE with conventional CE and review
      developments in this technique that may be useful in diagnosis of major diseases.

PMID- 16299049
TI  - Measurement of procarboxypeptidase U (TAFI) in human plasma: a laboratory
      challenge.
AB  - BACKGROUND: The importance of carboxypeptidase U (CPU) as a novel regulator of
      the fibrinolytic rate has attracted much interest during recent years. CPU
      circulates in plasma as a zymogen, proCPU, that can be activated by thrombin,
      thrombin-thrombomodulin (T-Tm), or plasmin. Given that the proCPU concentration
      in plasma is far below its K(m) for activation by the T-Tm complex, the formation
      of CPU will be directly proportional to the proCPU concentration. A low or high
      proCPU plasma concentration might therefore tip the balance between
      profibrinolytic and antifibrinolytic pathways and thereby cause a predisposition
      to bleeding or thrombosis. CONTENT: To measure plasma proCPU concentrations,
      different methods have been developed based on 2 different principles: antigen
      determination and measurement of CPU activity after quantitative conversion of
      the proenzyme to its active form by addition of T-Tm. The major drawbacks that
      should be kept in mind when analyzing clinical samples by both principles are
      reviewed. CONCLUSIONS: proCPU is a potential prothrombotic risk factor.
      Evaluation of its relationship with thrombosis requires accurate assays. Many
      assays used in different clinical settings are inadequately validated, forcing
      reconsideration of conclusions made in these reports.

PMID- 16299050
TI  - Performance characteristics of a novel tandem mass spectrometry assay for serum
      testosterone.
AB  - BACKGROUND: Commercial immunoassays for testosterone (Te) may give inaccurate
      results for samples from women and children, leading to misdiagnosis and
      inappropriate treatment. We developed a sensitive and specific tandem mass
      spectrometric assay for measurement of Te at the concentrations encountered in
      women and children. METHODS: Te was extracted with methyl tert-butyl ether from
      100 microL of serum or plasma, derivatized to form an oxime, and reextracted by
      solid-phase extraction. Instrumental analysis was performed on an API 4000 HPLC
      tandem mass spectrometer in the multiple-reaction monitoring (MRM) mode. The MRM
      transitions (m/z) were 304-->124 and 304-->112 for Te and 307-->124 and 307-->112
      for d3-Te. RESULTS: Within- and between-run CVs were <12% and 7.9%, respectively.
      The limit of quantification was 0.0346 nmol/L (1 ng/dL). Reference intervals for
      sex hormone-binding globulin and total, free, and bioavailable Te were
      established for children of Tanner stages 1 through 5 and adult males and
      females. CONCLUSIONS: The sensitivity and specificity of the method are adequate
      for analysis of Te in samples from women and children. The method requires small
      sample volumes, has adequate precision, and is not subject to interferences.

PMID- 16299051
TI  - Regulatory features of interleukin-1beta-mediated prostaglandin E2 synthesis in
      airway smooth muscle.
AB  - Exposure of airway smooth muscle (ASM) cells to the cytokine IL-1beta results in
      an induction of PGE2 synthesis that affects numerous cell functions. Current
      dogma posits induction of COX-2 protein as the critical, obligatory event in
      cytokine-induced PGE2 production, although PGE2 induction can be inhibited
      without a concomitant inhibition of COX-2. To explore other putative regulatory
      features we examined the role of phospholipase A2 (PLA2) and PGE synthase (PGES)
      enzymes in IL-1beta-induced PGE2 production. Treatment of human ASM cultures with
      IL-1beta caused a time-dependent induction of both cytosolic PLA2 (cPLA2) and
      microsomal PGES (mPGES) similar to that observed for COX-2. Regulation of COX-2
      and mPGES induction was similar, being significantly reduced by inhibition of
      p42/p44 or p38, whereas cPLA2 induction was only minimally reduced by inhibition
      of p38 or PKC. COX-2 and mPGES induction was subject to feed-forward regulation
      by PKA, whereas cPLA2 induction was not. SB-202474, an SB-203580 analog lacking
      the ability to inhibit p38 but capable of inhibiting IL-1beta-induced PGE2
      production, was effective in inhibiting mPGES but not COX-2 or cPLA2 induction.
      These data suggest that although COX-2, cPLA2, and mPGES are all induced by IL
      beta in human ASM cells, regulatory features of cPLA2 are dissociated, whereas
      those of COX-2 and mPGES are primarily associated, with regulation of PGE2
      production. mPGES induction and, possibly, cPLA2 induction appear to cooperate
      with COX-2 to determine IL-1beta-mediated PGE2 production in human ASM cells.

PMID- 16299052
TI  - Control of intracellular trafficking of ICAM-1-targeted nanocarriers by
      endothelial Na+/H+ exchanger proteins.
AB  - Targeting nanocarriers (NC) loaded by antioxidant enzymes (e.g., catalase) to
      endothelial cell adhesion molecules (CAM) alleviates oxidative stress in the
      pulmonary vasculature. However, antioxidant protection is transient, since CAM
      targeted catalase is internalized, delivered to lysosomes, and degraded. To
      design means to modulate the metabolism and longevity of endothelial cell (EC)
      targeted drugs, we identified and manipulated cellular elements controlling the
      uptake and intracellular trafficking of NC targeted to ICAM-1 (anti-ICAM/NC).
      BAPTA, thapsigargin, amiloride, and EIPA inhibited anti-ICAM/NC uptake by EC and
      actin rearrangements induced by anti-ICAM/NC (required for uptake), suggesting
      that member(s) of Na(+)/H(+) exchanger family proteins (NHE) regulate these
      processes. Consistent with this hypothesis, an siRNA specific for the plasmalemma
      NHE1, but not the endosome-associated NHE6, inhibited actin remodeling induced by
      anti-ICAM/NC and internalization. Anti-ICAM/NC binding to EC stimulated formation
      of a transient ICAM-1/NHE1 complex. One hour after uptake, ICAM-1 dissociated
      from NHE1, and anti-ICAM/NC were transported to NHE6-positive vesicles en route
      to lysosomes. Inhibition of PKC (an activator of intracellular NHE) accelerated
      nanocarrier lysosomal trafficking. In contrast, monensin, which enhances the
      endosomal sodium influx and proton efflux maintained by NHE6, inhibited delivery
      of anti-ICAM/NC to lysosomes by switching their trafficking to a plasma membrane
      recycling pathway. This markedly prolonged the protective effect of catalase
      coated anti-ICAM/NC. Therefore, 1) NHE1 and NHE6 regulate distinct phases of anti
      ICAM/NC uptake and trafficking; 2) pharmacological agents affecting these
      regulatory elements alter the itinerary of anti-ICAM/NC intracellular
      trafficking; and 3) these agents modulate duration of the therapeutic effects of
      targeted drugs.

PMID- 16299054
TI  - Iroquois genes influence proximo-distal morphogenesis during rat lung
      development.
AB  - Lung development is a highly regulated process directed by mesenchymal-epithelial
      interactions, which coordinate the temporal and spatial expression of multiple
      regulatory factors required for proper lung formation. The Iroquois homeobox
      (Irx) genes have been implicated in the patterning and specification of several
      Drosophila and vertebrate organs, including the heart. Herein, we investigated
      whether the Irx genes play a role in lung morphogenesis. We found that Irx1-3 and
      Irx5 expression was confined to the branching lung epithelium, whereas Irx4 was
      not expressed in the developing lung. Antisense knockdown of all pulmonary Irx
      genes together dramatically decreased distal branching morphogenesis and
      increased distention of the proximal tubules in vitro, which was accompanied by a
      reduction in surfactant protein C-positive epithelial cells and an increase in
      beta-tubulin IV and Clara cell secretory protein positive epithelial structures.
      Transmission electron microscopy confirmed the proximal phenotype of the
      epithelial structures. Furthermore, antisense Irx knockdown resulted in loss of
      lung mesenchyme and abnormal smooth muscle cell formation. Expression of
      fibroblast growth factors (FGF) 1, 7, and 10, FGF receptor 2, bone morphogenetic
      protein 4, and Sonic hedgehog (Shh) were not altered in lung explants treated
      with antisense Irx oligonucleotides. All four Irx genes were expressed in Shh-
      and Gli(2)-deficient murine lungs. Collectively, these results suggest that Irx
      genes are involved in the regulation of proximo-distal morphogenesis of the
      developing lung but are likely not linked to the FGF, BMP, or Shh signaling
      pathways.

PMID- 16299053
TI  - Nitric oxide induces phosphodiesterase 4B expression in rat pulmonary artery
      smooth muscle cells.
AB  - Phosphodiesterases (PDE) metabolize cyclic nucleotides limiting the effects of
      vasodilators such as prostacyclin and nitric oxide (NO). In this study, DNA
      microarray techniques were used to assess the impact of NO on expression of PDE
      genes in rat pulmonary arterial smooth muscle cells (rPASMC). Incubation of
      rPASMC with S-nitroso-l-glutathione (GSNO) increased expression of a PDE isoform
      that specifically metabolizes cAMP (PDE4B) in a dose- and time-dependent manner.
      GSNO increased PDE4B protein levels, and rolipram-inhibitable PDE activity was
      2.3 +/- 1.0-fold greater in GSNO-treated rPASMC than in untreated cells. The
      soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin
      1-one, and the cAMP-dependent protein kinase inhibitor, H89, prevented induction
      of PDE4B gene expression by GSNO, but the protein kinase G (PKG) inhibitors, Rp-8
      pCPT-cGMPs and KT-5823, did not. Incubation of rPASMC with IL-1beta and tumor
      necrosis factor-alpha induced PDE4B gene expression, an effect that was inhibited
      by l-N(6)-(1-iminoethyl)lysine, an antagonist of NO synthase 2 (NOS2). The GSNO
      induced increase in PDE4B mRNA levels was blocked by actinomycin D but augmented
      by cycloheximide. Infection of rPASMC with an adenovirus specifying a dominant
      negative cAMP response element binding protein (CREB) mutant inhibited the GSNO
      induced increase of PDE4B gene expression. These results suggest that exposure of
      rPASMC to NO induces expression of PDE4B via a mechanism that requires cGMP
      synthesis by sGC but not PKG. The GSNO-induced increase of PDE4B gene expression
      is CREB dependent. These findings demonstrate that NO increases expression of a
      cAMP-specific PDE and provide evidence for a novel "cross talk" mechanism between
      cGMP and cAMP signaling pathways.

PMID- 16299055
TI  - Pneumococci induced TLR- and Rac1-dependent NF-kappaB-recruitment to the IL-8
      promoter in lung epithelial cells.
AB  - Streptococcus pneumoniae is the major pathogen of community-acquired pneumonia.
      The respiratory epithelium constitutes the first line of defense against invading
      lung pathogens, including pneumococci. We analyzed the involvement of Toll-like
      receptors (TLR) and Rho-GTPase signaling in the activation of human lung
      epithelial cells by pneumococci. S. pneumoniae induced release of interleukin-8
      (IL-8) by human bronchial epithelial cell line BEAS-2B. Specific inhibition of
      Rac1 by Nsc23766 or a dominant-negative mutant of Rac1 strongly reduced cytokine
      release. In addition, pneumococci-related cell activation (IL-8 release, NF
      kappaB-activation) depended on MyD88, phosphatidylinositol 3-kinase, and Cdc42
      but not on RhoA. Pneumococci enhanced TLR1 and TLR2 mRNA expression in BEAS-2B
      cells, whereas TLR4 and TLR6 expression was constitutively high. TLR1 and 2
      synergistically recognized pneumococci in cotransfection experiments. TLR4, TLR6,
      LPS-binding protein, and CD14 seem not to be involved in pneumococci-dependent
      cell activation. At the IL-8 gene promoter, recruitment of phosphorylated NF
      kappaB subunit p65 was blocked by inhibition of Rac1, whereas binding of the
      phosphorylated activator protein-1 subunit c-Jun to the promoter was not
      diminished. In summary, these results suggest that S. pneumoniae activate human
      epithelial cells by TLR1/2 and a phosphatidylinositol 3-kinase- and Rac1
      dependent NF-kappaB-recruitment to the IL-8 promoter.

PMID- 16299056
TI  - Induction of secondary apoptosis, inflammation, and lung fibrosis after
      intratracheal instillation of apoptotic cells in rats.
AB  - Uncontrolled apoptosis has been associated with several pulmonary disorders;
      however, the molecular mechanism underlying this process and the fate of
      apoptotic cells in vivo are unclear. Here we show that direct administration of
      apoptotic cells to the lungs of rats caused pulmonary inflammation and fibrosis,
      as indicated by emigration of inflammatory cells to the air spaces, TNF-alpha
      immunoreactivity, and connective tissue accumulation, indicating a direct
      relationship between apoptotic cells and the observed lung pathologies. To
      determine how the lungs process the accumulated apoptotic cells, normal or
      apoptotic cells from autologous donor rats were labeled with fluorescent
      nanobeads and intratracheally instilled into the lungs of rats. Probe
      distribution and lung cell apoptosis were determined at various times over a 28
      day period by confocal fluorescence microscopy and terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling, respectively. Labeled apoptotic
      cells were cleared by lung macrophages within 1 wk after the treatment. However,
      the total number of apoptotic cells in the lung remained high at 28 days
      posttreatment. The results indicate a continuous induction of secondary apoptosis
      by apoptotic cell instillation, which may contribute to the observed lung
      pathology. Analysis of lung cell apoptosis by caspase assays showed an elevation
      of caspase-8 but not caspase-9 in the treatment group at 28 days posttreatment,
      indicating involvement of the death receptor-mediated pathway in the apoptotic
      process. Together, our results demonstrate a direct effect of apoptotic cell
      accumulation on inflammatory and fibrotic pulmonary responses and the continuous
      induction of lung cell apoptosis by apoptotic cell instillation.

PMID- 16299058
TI  - Molecularly-defined lactose malabsorption, milk consumption and anthropometric
      differences in adult males.
AB  - BACKGROUND: Lactose malabsorption (LM) may be associated with reduced skeletal
      calcium content. Diagnosis to date has been based on indirect methods, with a
      high false-negative rate. Identification of the LCT polymorphism led to
      development of a PCR-based test. AIM: To evaluate the PCR-based test compared to
      a combination the hydrogen breath test and the lactose tolerance test, and
      investigate anthropometrical differences, changes in bone mineral density and
      oral calcium intake according to LCT polymorphism and milk-drinking habits.
      METHODS: All participants (n = 278) underwent clinical examination, with
      measurement of height, weight and bone density (DXA), and were genotyped for LCT
      polymorphism (LCT CC or LCT TT: CC is associated with LM). A subgroup (n = 51)
      had a hydrogen breath test and a lactose tolerance test, in addition to
      genotyping. RESULTS: Detection of LM by LCT polymorphism was highly significant
      (p = 0.001). The correlation between LCT genotype and self-reported milk
      intolerance or dislike of milk with was slight, but the correlation with
      functional tests was highly significant. Non-milk-drinkers were lighter (-5 kg)
      and significantly shorter (-4 cm) than milk-drinkers (p = 0.07 and 0.04,
      respectively). Total calcium consumption was lower among non-milk-drinkers by
      about 18% (p = 0.03). DISCUSSION: Genotyping is an economic, quick and convenient
      method for diagnosing lactose malabsorption, with results comparable to existing
      tests. Sufficient calcium consumption may be relevant to body growth, as milk
      drinkers were taller. Negative calcium bone balance may be prevented when
      provision is made for adequate calcium intake.

PMID- 16299057
TI  - Contribution of proliferation and DNA damage repair to alveolar epithelial type 2
      cell recovery from hyperoxia.
AB  - In this study, C57BL/6J mice were exposed to hyperoxia and allowed to recover in
      room air. The sublethal dose of hyperoxia for C57BL/6J was 48 h. Distal lung
      cellular isolates from treated animals were characterized as 98% epithelial, with
      minor fibroblast and endothelial cell contaminants. Cells were then verified as
      95% pure alveolar epithelial type II cells (AEC2) by surfactant protein C (SP-C)
      expression. After hyperoxia exposure in vivo, fresh, uncultured AEC2 were
      analyzed for proliferation by cell yield, cell cycle, PCNA expression, and
      telomerase activity. DNA damage was assessed by TdT-dUTP nick-end labeling,
      whereas induction of DNA repair was evaluated by GADD-153 expression. A baseline
      level for proliferation and damage was observed in cells from control animals
      that did not alter significantly during acute hyperoxia exposure. However, a rise
      in these markers was observed 24 h into recovery. Over 72 h of recovery, markers
      for proliferation remained elevated, whereas those for DNA damage and repair
      peaked at 48 h and then returned back to baseline. The expression of GADD-153
      followed a distinct course, rising significantly during acute exposure and
      peaking at 48 h recovery. These data demonstrate that in healthy, adult male
      C57BL/6J mice, AEC2 proliferation, damage, and repair follow separate courses
      during hyperoxia recovery and that both proliferation and efficient repair may be
      required to ensure AEC2 survival.

PMID- 16299059
TI  - Where older people die: a retrospective population-based study.
AB  - BACKGROUND: Palliative medicine services have invested in the community to
      support people dying at home. To develop end-of-life care for older people, we
      need to know where they die. AIM: To examine trends in age and location of death
      over the last 20 years. DESIGN: Retrospective death certificate review. METHOD:
      All Wales death certificates from 1981 to 2001 were examined. Place of death and
      age were noted. RESULTS: Total deaths decreased from 35,015 in 1981 to 32,966 in
      2001, and mortality decreased from 12.45 per 1000 population in 1981 to 11.33 in
      2001. Deaths in the community decreased from 37.6% (n = 13,155) to 22.1% (n =
      7293) (p < 0.001); deaths increased in hospital from 56.7% (n = 19,871) to 61.7%
      (n = 20,334) (p < 0.001) and in care homes from 5.7% (n = 1989) to 16.2% (n =
      5339) (p < 0.001). Between 1981 and 2001, deaths in those aged 65-74 years
      dropped from 9752 to 6361, but increased in the over-85s from 5661 to 9779.
      Deaths amongst 75-84-year-olds remained stable at around 11,000. The biggest rise
      in hospital and care-home deaths was in those over 85: hospital deaths increased
      from 2928 in 1981, to 5438 in 2001; care-home deaths increased from 941 to 3141.
      DISCUSSION: The last 20 years have seen a significant shift in location of death
      from the community to hospitals and care homes. Those aged over 85 years account
      for the biggest rise in hospital and care-home deaths. End-of-life needs for
      older people need to be addressed in hospital and care homes, not just in the
      community.

PMID- 16299060
TI  - Bilateral renal artery stenosis and primary aldosteronism in a diabetic patient.

PMID- 16299061
TI  - Colonic diverticular haemorrhage is associated with atherosclerosis.

PMID- 16299062
TI  - Bone crisis in stable Gaucher's disease.

PMID- 16299063
TI  - Mysteries of the male.

PMID- 16299064
TI  - A filamin A splice mutation resulting in a syndrome of facial dysmorphism,
      periventricular nodular heterotopia, and severe constipation reminiscent of
      cerebro-fronto-facial syndrome.
AB  - BACKGROUND: Mutations of the filamin A locus (FLNA) on Xq28 have been established
      in girls with periventricular nodular heterotopia and in patients with
      otopalatodigital and overlapping phenotypes, the pathogenesis of these phenotypes
      being thought to be quite distinct. To date only six male cases of
      periventricular nodular heterotopia (PVNH) have been reported and these almost
      invariably associated with severe neurological signs. METHODS AND RESULTS: We
      report a new phenotype of male PVNH, with relatively normal development, no
      epilepsy or other neurological abnormality, severe constipation, and facial
      dysmorphism and without a discernible skeletal phenotype. This phenotype is
      associated with a splice site mutation in FLNA c.1923C>T, resulting in the
      generation of both normal and aberrant mRNA. CONCLUSIONS: We postulate that the
      patient retains enough FLNA function to avoid the usual lethality associated with
      loss of function mutations in males and suggest that the severe constipation may
      be a clue to the molecular aetiology of other X linked conditions associated with
      severe constipation.

PMID- 16299065
TI  - Variations in the complement regulatory genes factor H (CFH) and factor H related
      5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II
      (dense deposit disease).
AB  - INTRODUCTION: Membranoproliferative glomerulonephritis type II or dense deposit
      disease (MPGN II/DDD) causes chronic renal dysfunction that progresses to end
      stage renal disease in about half of patients within 10 years of diagnosis.
      Deficiency of and mutations in the complement factor H (CFH) gene are associated
      with the development of MPGN II/DDD, suggesting that dysregulation of the
      alternative pathway of the complement cascade is important in disease
      pathophysiology. SUBJECTS: Patients with MPGN II/DDD were studied to determine
      whether specific allele variants of CFH and CFHR5 segregate preferentially with
      the MPGN II/DDD disease phenotype. The control group was compromised of 131
      people in whom age related macular degeneration had been excluded. RESULTS:
      Allele frequencies of four single nucleotide polymorphisms in CFH and three in
      CFHR5 were significantly different between MPGN II/DDD patients and controls.
      CONCLUSION: We have identified specific allele variants of CFH and CFHR5
      associated with the MPGN II/DDD disease phenotype. While our data can be
      interpreted to further implicate complement in the pathogenesis of MPGN II/DDD,
      these associations could also be unrelated to disease pathophysiology. Functional
      studies are required to resolve this question.

PMID- 16299067
TI  - Molecular mechanisms of cannabinoid protection from neuronal excitotoxicity.
AB  - Cannabinoids protect neurons from excitotoxic injury. We investigated the
      mechanisms involved by studying N-methyl-D-aspartate (NMDA) toxicity in cultured
      murine cerebrocortical neurons in vitro and mouse cerebral cortex in vivo. The
      cannabinoid agonist R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)
      methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(1-naphthalenyl)-methanone mesylate
      [R(+)-Win 55212] reduced neuronal death in murine cortical cultures treated with
      20 microM NMDA, and its protective effect was attenuated by the CB1 cannabinoid
      receptor (CB1R) antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4
      cichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A).
      Cultures from CB1R-knockout mice were more sensitive to NMDA toxicity than were
      cultures from wild-type mice. The in vitro protective effect of R(+)-Win 55212
      was reduced by pertussis toxin, consistent with signaling through CB1R-coupled G
      proteins. The nitric-oxide synthase (NOS) inhibitors 7-nitroindazole (7-NI) and N
      omega-nitro-L-arginine methyl ester also reduced NMDA toxicity. In addition, CB1R
      and neuronal NOS were coexpressed in cultured cortical neurons, suggesting that
      cannabinoids might reduce NMDA toxicity by interfering with the generation of NO.
      NOS activity in cerebral cortex was higher in CB1R-knockouts than in wildtype
      mice, and 7-NI reduced NMDA lesion size. R(+)-Win 55212 inhibited NO production
      after NMDA treatment of wild-type cortical neuron cultures, measured with 4-amino
      5-methylamino-2',7'-difluorofluorescein diacetate, and this effect was reversed
      by SR141716A. In contrast, R(+)-Win 55212 failed to inhibit NO production in
      cultures from CB1R knockouts. Dibutyryl-cAMP blocked the protective effect of
      R(+)-Win 55212, and this was reversed by the protein kinase A (PKA) inhibitor N
      [2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide (H89). Cannabinoids
      seem to protect neurons against NMDA toxicity at least in part by activation of
      CB1R and downstream inhibition of PKA signaling and NO generation.

PMID- 16299068
TI  - Quantification and correction of systematic errors due to detector time-averaging
      in single-molecule tracking experiments.
AB  - Single-molecule tracking is a powerful way to look at the dynamic organization of
      plasma membranes. However, there are some limitations to its use. For example, it
      was recently observed, using numerical simulation, that time-averaging effects
      inherent to the exposure time of detectors are likely to bias the apparent motion
      of molecules confined in microdomains. Here, we solve this apparently limiting
      issue analytically. We explore this phenomenon by calculating its effects on the
      observed diffusion coefficients and domain sizes. We demonstrate that the real
      parameters can be easily recovered from the measured apparent ones.
      Interestingly, we find that single-molecule tracking can be used to explore
      events occurring at a timescale smaller than the exposure time.

PMID- 16299066
TI  - Oesophageal atresia, tracheo-oesophageal fistula, and the VACTERL association:
      review of genetics and epidemiology.
AB  - Oesophageal atresia and/or tracheo-oesophageal fistula are relatively common
      malformations occurring in approximately 1 in 3500 births. In around half of the
      cases (syndromic oesophageal atresia), there are associated anomalies, with
      cardiac malformations being the most common. In the remainder (non-syndromic
      cases), oesophageal atresia/tracheo-oesophageal fistula occur in isolation. Data
      from twin and family studies suggest that genetic factors do not play a major
      role, and yet there are well-defined instances of this malformation where genetic
      factors clearly are important. This is highlighted by the recent identification
      of no fewer than three separate genes with a role in the aetiology of oesophageal
      atresia: those for Feingold syndrome (N-MYC), anophthalmia-oesophageal-genital
      (AEG) syndrome (SOX2), and CHARGE syndrome (CHD7). Additional support for genetic
      factors in this malformation comes from chromosomal studies and mouse models.
      This paper reviews current knowledge of the genetics and epidemiology of the
      different oesophageal atresia/tracheo-oesophageal fistula syndromes and
      associations.

PMID- 16299070
TI  - Enhancement of diffusion-controlled reaction rates by surface-induced
      orientational restriction.
AB  - We explore the means by which immobilization of a substrate on a surface can
      increase the rate of a diffusion-controlled enzymatic reaction. A quasichemical
      approach is developed and compared with Brownian dynamics simulations. We use
      these methods to show that restricting only the orientation of the enzyme by long
      range interactions with the surface is sufficient for enhancing catalysis.

PMID- 16299069
TI  - 1H and 13C-NMR and molecular dynamics studies of cyclosporin a interacting with
      magnesium(II) or cerium(III) in acetonitrile. Conformational changes and cis
      trans conversion of peptide bonds.
AB  - Cyclosporin A (CsA) is an important drug used to prevent graft rejection in organ
      transplantations. Its immunosuppressive activity is related to the inhibition of
      T-cell activation through binding with the proteins Cyclophilin (Cyp) and,
      subsequently, Calcineurin (CN). In the complex with its target (Cyp), CsA adopts
      a conformation with all trans peptide bonds and this feature is very important
      for its pharmacological action. Unfortunately, CsA can cause several side
      effects, and it can favor the excretion of calcium and magnesium. To evaluate the
      possible role of conformational effects induced by these two metal ions in the
      action mechanism of CsA, its complexes with Mg(II) and Ce(III) (the latter as a
      paramagnetic probe for calcium) have been examined by two-dimensional NMR and
      relaxation rate analysis. The conformations of the two complexes and of the free
      form have been determined by restrained molecular dynamics calculations based on
      the experimentally obtained metal-proton and interproton distances. The findings
      here ratify the formation of 1:1 complexes of CsA with both Mg(II) and Ce(III),
      with metal coordination taking place on carbonyl oxygens and substantially
      altering the peptide structure with respect to the free form, although the
      residues involved and the resulting conformational changes, including cis-trans
      conversion of peptide bonds, are different for the two metals.

PMID- 16299071
TI  - Chemical modification of the bacterial porin OmpF: gain of selectivity by volume
      reduction.
AB  - OmpF is an essentially nonselective porin isolated from the outer membrane of
      Escherichia coli. Here we report on the manipulation of the ion selectivity of
      OmpF by chemical modification with MTS reagents (MTSET, MTSEA, and MTSES) and the
      (rather bulky) tripeptide glutathione, all cysteine specific. When recorded in a
      gradient of 0.1//1 M CaCl2 or 0.1//1 M NaCl, pH 7.4 solutions, measured reversal
      potentials of the most cation-selective modified mutants were (virtually)
      identical to the Nernst potential of Ca2+ or Na+. Compared to this full cation
      selectivity, the anion-selective modified mutants performed somewhat less but
      nevertheless showed high anion selectivity. We conclude that a low permanent
      charge in combination with a narrow pore can render the same selectivity as a
      highly charged but wider pore. These results favor the view that both the
      electrostatic potential arising form the fixed charge in the pore and the space
      available at the selectivity filter contribute to the charge selection (i.e.,
      cation versus anion selectivity) of a biological ion channel.

PMID- 16299072
TI  - Molecular shielding of electric field complex dissociation.
AB  - We have previously demonstrated the ability of electric fields to dissociate
      ascorbate and catecholamines and shown that the electric field generated by cell
      membranes is sufficient to produce dissociation of these complexes up to 8 nm
      from the cell membrane. We show here that this process is applicable to a wide
      range of biological complexes including small molecules (norepinephrine-morphine
      sulfate), protein-protein complexes (insulin-glucagon), and small molecule
      protein complexes (epinephrine-bovine serum albumin). The extrapolation of the
      slope of the electric field dependence to zero electric field can be used to
      estimate the log of the dissociation constant (K(D)) of a complex and, by
      multiplying the log(K(D)) by -2.303RT, the association energy (E) of the complex.
      The slope of the electric field dependence is inversely related to the molecular
      radii, with the best fit of the slope related to E*(1/r1 + 1/r2), where r is the
      estimated radius of each molecule in the complementary pair. This indicates that
      the binding site of the pair is shielded by the remaining parts of the molecules,
      and the larger the molecule the greater the shielding. When the slope of the
      electric field dependence goes to 0 as r goes to infinity and 1/r goes to 0, the
      molecular shielding constant is 7.04 x 10(-8) cm2/V. Very large complexes will be
      minimally affected by the electric field due to molecular shielding and reduced
      electric field as their radius restricts approach to the membrane. Large protein
      receptors will deflect the membrane electric field and allow agonist binding.

PMID- 16299073
TI  - Lipid headgroup discrimination by antimicrobial peptide LL-37: insight into
      mechanism of action.
AB  - Interaction of the human antimicrobial peptide LL-37 with lipid monolayers has
      been investigated by a range of complementary techniques including pressure-area
      isotherms, insertion assay, epifluorescence microscopy, and synchrotron x-ray
      scattering, to analyze its mechanism of action. Lipid monolayers were formed at
      the air-liquid interface to mimic the surface of the bacterial cell wall and the
      outer leaflet of erythrocyte cell membrane by using phosphatidylglycerol (DPPG),
      phosphatidylcholine (DPPC), and phosphatidylethanolamine (DPPE) lipids. LL-37 is
      found to readily insert into DPPG monolayers, disrupting their structure and thus
      indicating bactericidal action. In contrast, DPPC and DPPE monolayers remained
      virtually unaffected by LL-37, demonstrating its nonhemolytic activity and lipid
      discrimination. Specular x-ray reflectivity data yielded considerable differences
      in layer thickness and electron-density profile after addition of the peptide to
      DPPG monolayers, but little change was seen after peptide injection when probing
      monolayers composed of DPPC and DPPE. Grazing incidence x-ray diffraction
      demonstrated significant peptide insertion and lateral packing order disruption
      of the DPPG monolayer by LL-37 insertion. Epifluorescence microscopy data support
      these findings.

PMID- 16299074
TI  - Tension recovery in permeabilized rat soleus muscle fibers after rapid shortening
      and restretch.
AB  - Permeabilized rat soleus muscle fibers were subjected to rapid
      shortening/restretch protocols (20% muscle length, 20 ms duration) in solutions
      with pCa values ranging from 6.5 to 4.5. Force redeveloped after each restretch
      but temporarily exceeded the steady-state isometric tension reaching a maximum
      value approximately 2.5 s after relengthening. The relative size of the overshoot
      was <5% in pCa 6.5 and pCa 4.5 solutions but equaled 17% +/- 4% at pCa 6.0
      (approximately half-maximal Ca2+ activation). Muscle stiffness was estimated
      during pCa 6.0 activations by imposing length steps at different time intervals
      after repeated shortening/restretch perturbations. Relative stiffness and
      relative tension were correlated (p < 0.001) during recovery, suggesting that
      tension overshoots reflect a temporary increase in the number of attached cross
      bridges. Rates of tension recovery (k(tr)) correlated (p < 0.001) with the
      relative residual force prevailing immediately after restretch. Force also
      recovered to the isometric value more quickly at 5.7 < or = pCa < or = 5.9 than
      at pCa 4.5 (ANOVA, p < 0.05). These results show that k(tr) measurements
      underestimate the rate of isometric force development during submaximal Ca2+
      activations and suggest that the rate of tension recovery is limited primarily by
      the availability of actin binding sites.

PMID- 16299075
TI  - Genome-scale thermodynamic analysis of Escherichia coli metabolism.
AB  - Genome-scale metabolic models are an invaluable tool for analyzing metabolic
      systems as they provide a more complete picture of the processes of metabolism.
      We have constructed a genome-scale metabolic model of Escherichia coli based on
      the iJR904 model developed by the Palsson Laboratory at the University of
      California at San Diego. Group contribution methods were utilized to estimate the
      standard Gibbs free energy change of every reaction in the constructed model.
      Reactions in the model were classified based on the activity of the reactions
      during optimal growth on glucose in aerobic media. The most thermodynamically
      unfavorable reactions involved in the production of biomass in E. coli were
      identified as ATP phosphoribosyltransferase, ATP synthase, methylene-tetra
      hydrofolate dehydrogenase, and tryptophanase. The effect of a knockout of these
      reactions on the production of biomass and the production of individual biomass
      precursors was analyzed. Changes in the distribution of fluxes in the cell after
      knockout of these unfavorable reactions were also studied. The methodologies and
      results discussed can be used to facilitate the refinement of the feasible ranges
      for cellular parameters such as species concentrations and reaction rate
      constants.

PMID- 16299078
TI  - Pressure effects on the structure and phase behavior of DMPC-gramicidin lipid
      bilayers: a synchrotron SAXS and 2H-NMR spectroscopy study.
AB  - The influence of Gramicidin D (GD) incorporation on the structure and phase
      behavior of aqueous dispersions of DMPC lipid bilayers has been studied using
      small-angle x-ray scattering (SAXS) and (2)H-NMR spectroscopy. The experiments
      covered a temperature range from -10 degrees C to 60 degrees C and a pressure
      range of 0.001-4 kbar. Pressure was used to be able to tune the lipid bilayer
      conformational order and phase state and because high pressure is an important
      feature of certain natural biotopes. The data show that, depending on the GD
      concentration, the structure of the temperature- and pressure-dependent lipid
      phases is significantly altered by the insertion of the polypeptide, and a p,T
      phase diagram could be obtained for intermediate GD concentrations. Upon
      gramicidin insertion, a rather narrow fluid-gel coexistence regions is formed.
      Two gel phases are induced which are different from those of the pure lipid
      bilayer system and which separate at low temperatures/high pressures. For both
      the temperature- and pressure-induced fluid-to-gel transition, a similar
      pseudocritical transitional behavior is observed, which is even more pronounced
      upon incorporation of the peptide.

PMID- 16299077
TI  - Nucleic acid helix stability: effects of salt concentration, cation valence and
      size, and chain length.
AB  - Metal ions play crucial roles in thermal stability and folding kinetics of
      nucleic acids. For ions (especially multivalent ions) in the close vicinity of
      nucleic acid surface, interion correlations and ion-binding mode fluctuations may
      be important. Poisson-Boltzmann theory ignores these effects whereas the recently
      developed tightly bound ion (TBI) theory explicitly accounts for these effects.
      Extensive experimental data demonstrate that the TBI theory gives improved
      predictions for multivalent ions (e.g., Mg2+) than the Poisson-Boltzmann theory.
      In this study, we use the TBI theory to investigate how the metal ions affect the
      folding stability of B-DNA helices. We quantitatively evaluate the effects of ion
      concentration, ion size and valence, and helix length on the helix stability.
      Moreover, we derive practically useful analytical formulas for the thermodynamic
      parameters as functions of finite helix length, ion type, and ion concentration.
      We find that the helix stability is additive for high ion concentration and long
      helix and nonadditive for low ion concentration and short helix. All these
      results are tested against and supported by extensive experimental data.

PMID- 16299079
TI  - A two-photon excitation fluorescence cross-correlation assay for a model ligand
      receptor binding system using quantum dots.
AB  - Two-photon excitation fluorescence cross-correlation spectroscopy (TPE-XCS) is a
      very suitable method for studying interactions of two distinctly labeled
      fluorescent molecules. As such, it lends itself nicely to the study of ligand
      receptor interactions. By labeling the ligand with one color of fluorescent dye
      and the receptor with another, it is possible to directly monitor ligand binding
      rather than inferring binding by monitoring downstream effects. One challenge of
      the TPE-XCS approach is that of separating the signal due to the receptor from
      that of the ligand. Using standard organic fluorescent labels there is almost
      inevitably spectral cross talk between the detection channels, which must be
      accounted for in TPE-XCS data analysis. However, using quantum dots as labels for
      both ligand and receptor this limitation can be alleviated, because of the dot's
      narrower emission spectra. Using solely quantum dots as fluorescent labels is a
      novel approach to TPE-XCS, which may be generalizable to many pairs of
      interacting biomolecules after the proof of principle and the assessment of
      limitations presented here. Moreover, it is essential that relevant
      pharmacological parameters such as the equilibrium dissociation constant, K(d),
      can be easily extracted from the XCS data with minimal processing. Herein, we
      present a modified expression for fractional occupancy based on the auto- and
      cross-correlation decays obtained from a well-defined ligand-receptor system.
      Nanocrystalline semiconductor quantum dots functionalized with biotin (lambda(em)
      = 605 nm) and streptavidin (lambda(em) = 525 nm) were used for which an average
      K(d) value of 0.30 +/- 0.04 x 10(-9) M was obtained (cf. native system
      approximately 10(-15)). Additionally, the off-rate coefficient (k(off)) for
      dissociation of the two quantum dots was determined as 5 x 10(-5) s(-1). This off
      rate is slightly larger than for native biotin-streptavidin (5 x 10(-6) s(-1));
      the bulky nature of the quantum dots and restricted motion/orientation of
      functionalized dots in solution can account for differences in the streptavidin
      biotin mediated dot-dot binding compared with those for native streptavidin
      biotin.

PMID- 16299076
TI  - Binding-linked protonation of a DNA minor-groove agent.
AB  - The energetics for binding of a diphenyl diamidine antitrypanosomal agent CGP
      40215A to DNA have been studied by spectroscopy, isothermal titration
      calorimetry, and surface plasmon resonance biosensor methods. Both amidines are
      positively charged under experimental conditions, but the linking group for the
      two phenyl amidines has a pK(a) of 6.3 that is susceptible to a protonation
      process. Spectroscopic studies indicate an increase of 2.7 pK(a) units in the
      linking group when the compound binds to an A/T minor-groove site. Calorimetric
      titrations in different buffers and pH conditions support the proton-linkage
      process and are in a good agreement with spectroscopic titrations. The two
      methods established a proton-uptake profile as a function of pH. The exothermic
      enthalpy of complex formation varies with different pH conditions. The observed
      binding enthalpy increases as a function of temperature indicating a negative
      heat capacity change that is typical for DNA minor-groove binders. Solvent
      accessible surface area calculations suggest that surface burial accounts for
      about one-half of the observed intrinsic negative heat capacity change. Biosensor
      and calorimetric experiments indicate that the binding affinities vary with pH
      values and salt concentrations due to protonation and electrostatic interactions.
      The surface plasmon resonance binding studies indicate that the charge density
      per phosphate in DNA hairpins is smaller than that in polymers. Energetic
      contributions from different factors were also estimated for the ligand/DNA
      complex.

PMID- 16299080
TI  - Bistability explains threshold phenomena in protein aggregation both in vitro and
      in vivo.
AB  - Neurodegenerative disease can originate from the misfolding and aggregation of
      proteins, such as Amyloid-beta, SOD1, or Huntingtin. Fortunately, all cells
      possess protein quality control machinery that sequesters misfolded proteins,
      either refolding or degrading them, before they can self-associate into
      proteotoxic oligomers and aggregates. This activity is largely performed by the
      stress response chaperones (i.e., Hsp70). However, the expression level of
      molecular chaperones varies widely among cell types. To understand the potential
      consequence of this variation, we studied the process of protein aggregation in
      the presence of molecular chaperones using mathematical modeling. We demonstrate
      that protein aggregation, in the presence of molecular chaperones, is a bistable
      process. Bistability in protein aggregation offers an explanation for threshold
      transitions to high aggregate concentration, which are observed both in vitro and
      in vivo. Additionally, we show that slight variations in chaperone concentration,
      due to natural fluctuations, have important consequences in a bistable system for
      the onset of protein aggregation. Therefore, our results offer a possible
      theoretical explanation for neuronal vulnerability observed in vivo and the onset
      of neurodegenerative phenotypes in neurons lacking an effective heat-shock
      response.

PMID- 16299081
TI  - On the effect of prestin on the electrical breakdown of cell membranes.
AB  - The voltage-dependent activity of prestin, the outer hair cell (OHC) motor
      protein essential for its electromotility, enhances the mammalian inner ear's
      auditory sensitivity. We investigated the effect of prestin's activity on the
      plasma membrane's (PM) susceptibility to electroporation (EP) via cell-attached
      patch-clamping. Guinea pig OHCs, TSA201 cells, and prestin-transfected TSA cells
      were subjected to incremental 50 mus and/or 50 ms voltage pulse trains, or ramps,
      at rates from 10 V/s to 1 kV/s, to a maximum transmembrane potential of +/-1000
      mV. EP was determined by an increase in capacitance to whole-cell levels. OHCs
      were probed at the prestin-rich lateral PM or prestin-devoid basal portion; TSA
      cells were patched at random points. OHCs were consistently electroporated with
      50 ms pulses, with significant resistance to depolarizing pulses. Although EP
      rarely occurred with 50 mus pulses, prior stimulation with this protocol had a
      significant effect on the sensitivity to EP with 50 ms pulses, regardless of
      polarity or PM domain. Consistent with these results, resistance to EP with
      depolarizing 10-V/s ramps was also found. Our findings with TSA cells were
      comparable, showing resistance to EP with both depolarizing 50-ms pulses and 10
      V/s ramps. We conclude prestin significantly affects susceptibility to EP,
      possibly via known biophysical influences on specific membrane capacitance and/or
      membrane stiffness.

PMID- 16299082
TI  - Cell population dynamics modulate the rates of tissue growth processes.
AB  - The development and testing of a discrete model describing the dynamic process of
      tissue growth in three-dimensional scaffolds is presented. The model considers
      populations of cells that execute persistent random walks on the computational
      grid, collide, and proliferate until they reach confluence. To isolate the effect
      of population dynamics on tissue growth, the model assumes that nutrient and
      growth factor concentrations remain constant in space and time. Simulations start
      either by distributing the seed cells uniformly and randomly throughout the
      scaffold, or from an initial condition designed to simulate the migration and
      cell proliferation phase of wound healing. Simulations with uniform seeding show
      that cell migration enhances tissue growth by counterbalancing the adverse
      effects of contact inhibition. This beneficial effect, however, diminishes and
      disappears completely for large migration speeds. By contrast, simulations with
      the "wound" seeding mode show a continual enhancement of tissue regeneration
      rates with increasing cell migration speeds. We conclude that cell locomotory
      parameters and the spatial distribution of seed cells can have profound effects
      on the dynamics of the process and, consequently, on the pattern and rates of
      tissue growth. These results can guide the design of experiments for testing the
      effectiveness of biomimetic modifications for stimulating tissue growth.

PMID- 16299083
TI  - An algorithmic framework for genome-wide modeling and analysis of translation
      networks.
AB  - The sequencing of genomes of several organisms and advances in high throughput
      technologies for transcriptome and proteome analysis has allowed detailed
      mechanistic studies of transcription and translation using mathematical
      frameworks that allow integration of both sequence-specific and kinetic
      properties of these fundamental cellular processes. To understand how
      perturbations in mRNA levels affect the synthesis of individual proteins within a
      large protein synthesis network, we consider here a genome-scale codon-wide model
      of the translation machinery with explicit description of the processes of
      initiation, elongation, and termination. The mechanistic codon-wide description
      of the translation process and the large number of mRNAs competing for resources,
      such as ribosomes, requires the use of novel efficient algorithmic approaches. We
      have developed such an efficient algorithmic framework for genome-scale models of
      protein synthesis. The mathematical and computational framework was applied to
      the analysis of the sensitivity of a translation network to perturbation in the
      rate constants and in the mRNA levels in the system. Our studies suggest that the
      highest specific protein synthesis rate (protein synthesis rate per mRNA
      molecule) is achieved when translation is elongation-limited. We find that the
      mRNA species with the highest number of actively translating ribosomes exerts
      maximum control on the synthesis of every protein, and the response of protein
      synthesis rates to mRNA expression variation is a function of the strength of
      initiation of translation at different mRNA species. Such quantitative
      understanding of the sensitivity of protein synthesis to the variation of mRNA
      expression can provide insights into cellular robustness mechanisms and guide the
      design of protein production systems.

PMID- 16299084
TI  - Effect of average phospholipid curvature on supported bilayer formation on glass
      by vesicle fusion.
AB  - The adsorption of large unilamellar vesicles composed of various combinations of
      phosphatidylcholine, phosphatidylethanolamine (PE), monomethyl PE, and dimethyl
      PE (PE-Me2) onto a glass surface was studied using fluorescence microscopy. The
      average lipid geometry within the vesicles, described mathematically by the
      average intrinsic curvature, C(0,ave), was methodically altered by changing the
      lipid ratios to determine the effect of intrinsic curvature on the ability of
      vesicles to rupture and form a supported lipid bilayer. We show that the ability
      of vesicles to create fluid planar bilayers is dependent on C(0,ave) and
      independent of the identity of the component lipids. When the C(0,ave) was
      approximately -0.1 nm(-1), the vesicles readily formed supported lipid bilayers
      with almost full mobility. In contrast, when the C(0,ave) ranged from
      approximately -0.2 to approximately -0.3 nm(-1), the adsorbed vesicles remained
      intact upon the surface. The results indicate that the average shape of lipid
      molecules within a vesicle (C(0,ave)) is essential for determining kinetically
      viable reactions that are responsible for global geometric changes.

PMID- 16299085
TI  - Direct observation of abortive initiation and promoter escape within single
      immobilized transcription complexes.
AB  - Using total-internal-reflection fluorescence microscopy equipped with alternating
      laser excitation, we were able to detect abortive initiation and promoter escape
      within single immobilized transcription complexes. Our approach uses fluorescence
      resonance energy transfer to monitor distances between a fluorescent probe
      incorporated in RNA polymerase (RNAP) and a fluorescent probe incorporated in
      DNA. We observe small, but reproducible and abortive-product-length-dependent,
      decreases in distance between the RNAP leading edge and DNA downstream of RNAP
      upon abortive initiation, and we observe large decreases in distance upon
      promoter escape. Inspection of population distributions and single-molecule time
      traces for abortive initiation indicates that, at a consensus promoter, at
      saturating ribonucleoside triphosphate concentrations, abortive-product release
      is rate-limiting (i.e., abortive-product synthesis and RNAP-active-center forward
      translocation are fast, whereas abortive-product dissociation and RNAP-active
      center reverse translocation are slow). The results obtained using this new
      methodology confirm and extend those obtained from diffusing single molecules,
      and pave the way for real-time, single-molecule observations of the transitions
      between various states of the transcription complex throughout transcription.

PMID- 16299087
TI  - The importance of observational methods for evaluation of interventions to
      prevent occupational injuries.

PMID- 16299086
TI  - Molecular Dynamics Simulation of WSK-3, a Computationally Designed, Water-Soluble
      Variant of the Integral Membrane Protein KcsA.
AB  - Poor solubility and low expression levels often make membrane proteins difficult
      to study. An alternative to the use of detergents to solubilize these aggregation
      prone proteins is the partial redesign of the sequence so as to confer water
      solubility. Recently, computationally assisted membrane protein solubilization
      (CAMPS) has been reported, where exposed hydrophobic residues on a protein's
      surface are computationally redesigned. Herein, the structure and fluctuations of
      a designed, water-soluble variant of KcsA (WSK-3) were studied using molecular
      dynamics simulations. The root mean square deviation of the protein from its
      starting structure, where the backbone coordinates are those of KcsA, was 1.8
      angstroms. The structure of salt bridges involved in structural specificity and
      solubility were examined. The preferred configuration of ions and water in the
      selectivity filter of WSK-3 was consistent with the reported preferences for
      KcsA. The structure of the selectivity filter was maintained, which is consistent
      with WSK-3 having an affinity for agitoxin2 comparable to that of wild-type KcsA.
      In contrast to KcsA, the central cavity's side chains were observed to reorient,
      allowing water diffusion through the side of the cavity wall. These simulations
      provide an atomistic analysis of the CAMPS strategy and its implications for
      further investigations of membrane proteins.

PMID- 16299088
TI  - Protecting waste collectors all around the world.

PMID- 16299089
TI  - An updated study of mortality among North American synthetic rubber industry
      workers.
AB  - AIM: This study evaluated the mortality experience of workers from the styrene
      butadiene industry. METHODS: The authors added seven years of follow up to a
      previous investigation of mortality among 17 924 men employed in the North
      American synthetic rubber industry. Analyses used the standardised mortality
      ratios (SMRs) to compare styrene-butadiene rubber workers' cause specific
      mortality (1943-98) with those of the United States and the Ontario general
      populations. RESULTS: Overall, the observed/expected numbers of deaths were
      6237/7242 for all causes (SMR = 86, 95% CI 84 to 88) and 1608/1741 for all
      cancers combined (SMR = 92, 95% CI 88 to 97), 71/61 for leukaemia, 53/53 for non
      Hodgkin's lymphoma, and 26/27 for multiple myeloma. The 16% leukaemia increase
      was concentrated in hourly paid subjects with 20-29 years since hire and 10 or
      more years of employment in the industry (19/7.4, SMR = 258, 95% CI 156 to 403)
      and in subjects employed in polymerisation (18/8.8, SMR = 204, 95% CI 121 to
      322), maintenance labour (15/7.4, SMR = 326, 95% CI 178 to 456), and laboratory
      operations (14/4.3, SMR = 326, 95% CI 178-546). CONCLUSION: The study found that
      some subgroups of synthetic rubber workers had an excess of mortality from
      leukaemia that was not limited to a particular form of leukaemia. Uncertainty
      remains about the specific agent(s) that might be responsible for the observed
      excesses and about the role of unidentified confounding factors. The study did
      not find any clear relation between employment in the industry and other forms of
      lymphohaematopoietic cancer. Some subgroups of subjects had more than expected
      deaths from colorectal and prostate cancers. These increases did not appear to be
      related to occupational exposure in the industry.

PMID- 16299090
TI  - Prevention of work related eye injuries: long term assessment of the
      effectiveness of a multicomponent intervention among metal workers.
AB  - BACKGROUND: Systematic assessments of the effectiveness of interventions to
      prevent work related eye injuries are needed. AIM: To investigate the long term
      effectiveness of a multicomponent prevention campaign. METHODS: The campaign
      (conducted in collaboration with the local Employers' Association and Trade
      Unions) targeted all 237 metal-ware factories in the district of Imola, Italy.
      Based on preliminary inspections, the main intervention included distribution to
      all factories of specific educational brochures and broadcasting/publication of
      television/radio programmes and local newspaper articles containing expert advice
      on the subject. This was followed by a four year "post-intervention
      reinforcement" period of unannounced official inspections. Main outcome measures
      analysed were eye injury rates (versus non-eye injury rates) among metal workers
      during "pre-intervention" (1988-90), "peri-intervention" (1991-92), "post
      intervention reinforcement" (1993-96), "late post-intervention" (1997-2000), and
      "very late post-intervention" (2001-03) periods with respect to two comparison
      sectors (construction and wood/ceramics). RESULTS: A Poisson regression in which
      the eye injury rates were modelled for each sector, period, and interaction,
      adjusting for non-eye injury rates, was chosen. The periods did not by themselves
      determine an overall reduction in eye injuries. The period/sector interaction
      terms were related to significant reductions for the metal sector when crossed
      with the "post-intervention reinforcement" (IRR = 0.77, 95% CI 0.61 to 0.97; %
      decline = 23.4), the "late post-intervention" (IRR = 0.63, 95% CI 0.50 to 0.79; %
      decline = 37.4), and the "very late post-intervention" (IRR = 0.58, 95% CI 0.43
      to 0.77; % decline = 42.4) periods, suggesting a sustained reduction in eye
      injury risk following the main intervention. CONCLUSION: Results suggest that a
      carefully coordinated, extensive, multicomponent intervention can lead to lasting
      reductions in the burden of eye injuries.

PMID- 16299091
TI  - Incidence by occupation and industry of acute work related respiratory diseases
      in the UK, 1992-2001.
AB  - AIMS: To summarise incidence rates and epidemiological characteristics of new
      cases of work related respiratory disease reported by specialist physicians in
      thoracic and occupational medicine, with particular reference to occupation,
      industry, and causal agents for asthma, inhalation accidents, and allergic
      alveolitis. METHODS: Cases reported 1992-2001 to the SWORD and OPRA national
      surveillance schemes, in which almost all UK chest and occupational physicians
      participate, were analysed by age, sex, cause, occupation, and industry, with
      incidence rates calculated against appropriate denominators. RESULTS: Excluding
      diseases of long latency, infrequently seen by occupational physicians, the
      distribution of diagnoses in the two specialties was similar, but with rates
      generally much higher in occupational than chest physicians. Occupational asthma
      was responsible for about 25% of cases overall, affecting mainly craft related
      occupations and machinists, and most often attributed to isocyanates, metals,
      grains, wood dusts, solders, and welding fume. These same occupations were those
      at highest risk from inhalation injuries, most frequently caused by irritant
      gases, vapours, and fume. Among medical technicians and nurses, however,
      glutaraldehyde and latex were the main causes of occupational asthma. Allergic
      alveolitis was seldom reported, with almost all cases in agriculture, forestry,
      and fishing. CONCLUSION: During the 10 year period studied, there were few
      changes in level of reported incidence, apart from some decline in occupational
      asthma and inhalation injuries. These results and their implications should be
      distinguished from much higher estimates of asthma made worse by work derived
      from population surveys, based on prevalence rather than incidence, and self
      reported symptoms rather than diagnoses made by specialist physicians. Even so,
      the reported incidence of new cases of acute respiratory illness caused by work
      remains substantial.

PMID- 16299092
TI  - The threat to scientific integrity in environmental and occupational medicine.
AB  - Over the last century, environmental and occupational medicine has played a
      significant role in the protection and improvement of public health. However,
      scientific integrity in this field has been increasingly threatened by pressure
      from some industries and governments. For example, it has been reported that the
      tobacco industry manipulated eminent scientists to legitimise their industrial
      positions, irresponsibly distorted risk and deliberately subverted scientific
      processes, and influenced many organisations in receipt of tobacco funding. Many
      environmental whistleblowers were sued and encountered numerous personal attacks.
      In some countries, scientific findings have been suppressed and distorted, and
      scientific advisory committees manipulated for political purposes by government
      agencies. How to respond to these threats is an important challenge for
      environmental and occupational medicine professionals and their societies. The
      authors recommend that professional organisations adopt a code of ethics that
      requires openness from public health professionals; that they not undertake
      research or use data where they do not have freedom to publish their results if
      these data have public health implications; that they disclose all possible
      conflicts; that the veracity of their research results should not be compromised;
      and that their research independence be protected through professional and legal
      support. The authors furthermore recommend that research funding for public
      health not be directly from the industry to the researcher. An independent,
      intermediate funding scheme should be established to ensure that there is no
      pressure to analyse data and publish results in bad faith. Such a funding system
      should also provide equal competition for funds and selection of the best
      proposals according to standard scientific criteria.

PMID- 16299093
TI  - Prolonged standing at work and hospitalisation due to varicose veins: a 12 year
      prospective study of the Danish population.
AB  - BACKGROUND: Recent studies suggest that prolonged standing at work is associated
      with the development of diseases of varicose veins (VV). AIMS: To assess the risk
      of hospitalisation due to VV in the lower extremities prospectively in workers
      standing or walking at least 75% of their time at work. METHODS: A representative
      random sample of 9653 working age adults was drawn from the Central Population
      Register of Denmark in 1991. Of these, 8664 accepted to be interviewed by
      telephone (response rate 90%). Respondents (2939 men and 2708 women) were 20-59
      years old and employed in 1990. Risk ratios for VV were estimated by log-linear
      Poisson regression models separately for men and women with adjustment for
      smoking status, body mass index (BMI), heavy lifting, and, for females only,
      number of children at baseline. RESULTS: During 12 years of follow up, 40
      hospitalisations due to VV were observed among the men and 71 among the women.
      For employees with jobs that require prolonged standing or walking compared to
      all other employees, the relative risk was 1.75 (95% CI 0.92 to 3.34) for men and
      1.82 (95% CI 1.12 to 2.95) for women. The pooled estimate of the relative risk
      was 1.78 (95% CI 1.19 to 2.68). The aetiological fraction of prolonged standing
      or walking at work was estimated as 22.5% for men and 22.6% for women.
      CONCLUSIONS: This prospective study confirms that prolonged standing at work
      constitutes an excess risk of hospital treatment due to varicose veins and
      accounts for more than one fifth of all cases of working age.

PMID- 16299094
TI  - Prognostic factors for duration of sick leave in patients sick listed with acute
      low back pain: a systematic review of the literature.
AB  - BACKGROUND: The percentages of patients with acute low back pain (LBP) that go on
      to a chronic state varies between studies from 2% to 34%. In some of these cases
      low back pain leads to great costs. AIMS: To evaluate the evidence for prognostic
      factors for return to work among workers sick listed with acute LBP. METHODS:
      Systematic literature search with a quality assessment of studies, assessment of
      levels of evidence for all factors, and pooling of effect sizes. RESULTS:
      Inclusion of studies in the review was restricted to inception cohort studies of
      workers with LBP on sick leave for less than six weeks, with the outcome measured
      in absolute terms, relative terms, survival curve, or duration of sick leave. Of
      the studies, 18 publications (14 cohorts) fulfilled all inclusion criteria. One
      low quality study, four moderate quality studies, and nine high quality studies
      were identified; 79 prognostic factors were studied and grouped in eight
      categories for which the evidence was assessed. CONCLUSIONS: Specific LBP, higher
      disability levels, older age, female gender, more social dysfunction and more
      social isolation, heavier work, and receiving higher compensation were identified
      as predictors for a longer duration of sick leave. A history of LBP, job
      satisfaction, educational level, marital status, number of dependants, smoking,
      working more than 8 hour shifts, occupation, and size of industry or company do
      not influence duration of sick leave due to LBP. Many different constructs were
      measured to identify psychosocial predictors of long term sick leave, which made
      it impossible to determine the role of these factors.

PMID- 16299095
TI  - Incidence of haematopoietic malignancies in US radiologic technologists.
AB  - BACKGROUND: There are limited data on risks of haematopoietic malignancies
      associated with protracted low-to-moderate dose radiation. AIMS: To contribute
      the first incidence risk estimates for haematopoietic malignancies in relation to
      work history, procedures, practices, and protective measures in a large
      population of mostly female medical radiation workers. METHODS: The investigators
      followed up 71,894 (77.9% female) US radiologic technologists, first certified
      during 1926-80, from completion of a baseline questionnaire (1983-89) to return
      of a second questionnaire (1994-98), diagnosis of a first cancer, death, or 31
      August 1998 (731,306 person-years), whichever occurred first. Cox proportional
      hazards regression was used to compute risks. RESULTS: Relative risks (RR) for
      leukaemias other than chronic lymphocytic leukaemia (non-CLL, 41 cases) were
      increased among technologists working five or more years before 1950 (RR = 6.6,
      95% CI 1.0 to 41.9, based on seven cases) or holding patients 50 or more times
      for x ray examination (RR = 2.6, 95% CI 1.3 to 5.4). Risks of non-CLL leukaemias
      were not significantly related to the number of years subjects worked in more
      recent periods, the year or age first worked, the total years worked, specific
      procedures or equipment used, or personal radiotherapy. Working as a radiologic
      technologist was not significantly linked with risk of multiple myeloma (28
      cases), non-Hodgkin's lymphoma (118 cases), Hodgkin's lymphoma (31 cases), or
      chronic lymphocytic leukaemia (23 cases). CONCLUSION: Similar to results for
      single acute dose and fractionated high dose radiation exposures, there was
      increased risk for non-CLL leukaemias decades after initial protracted radiation
      exposure that likely cumulated to low-to-moderate doses.

PMID- 16299096
TI  - Associations between ambient, personal, and indoor exposure to fine particulate
      matter constituents in Dutch and Finnish panels of cardiovascular patients.
AB  - AIMS: To assess the relation between ambient, indoor, and personal levels of
      PM2.5 and its elemental composition for elderly subjects with cardiovascular
      disease. METHODS: In the framework of a European Union funded study, panel
      studies were conducted in Amsterdam, the Netherlands and Helsinki, Finland.
      Outdoor PM2.5 concentrations were measured at a fixed site. Each subject's indoor
      and personal PM2.5 exposure was measured biweekly for six months, during the 24
      hour period preceding intensive health measurements. The absorbance of PM2.5
      filters was measured as a marker for diesel exhaust. The elemental content of
      more than 50% of the personal and indoor samples and all corresponding outdoor
      samples was measured using energy dispersive x ray fluorescence. RESULTS: For
      Amsterdam and Helsinki respectively, a total of 225 and 238 personal, and 220 and
      233 indoor measurements, were analysed from 36 and 46 subjects. For most
      elements, personal and indoor concentrations were lower than and highly
      correlated with outdoor concentrations. The highest correlations (median r>0.9)
      were found for sulfur and particle absorbance, which both represent fine mode
      particles from outdoor origin. Low correlations were observed for elements that
      represent the coarser part of the PM2.5 particles (Ca, Cu, Si, Cl). CONCLUSIONS:
      The findings of this study provide support for using fixed site measurements as a
      measure of exposure to particulate matter in time series studies linking the day
      to day variation in particulate matter to the day to day variation in health
      endpoints, especially for components of particulate matter that are generally
      associated with fine particles and have few indoor sources. The high correlation
      for absorbance of PM2.5 documents that this applies to particulate matter from
      combustion sources, such as diesel vehicles, as well.

PMID- 16299097
TI  - Serum DDT, age at menarche, and abnormal menstrual cycle length.
AB  - BACKGROUND: Although dichlorodiphenyl trichloroethane (DDT) exposure is known to
      affect human endocrine function, few previous studies have investigated the
      effects of DDT exposure on age at menarche or menstrual cycle length. METHODS: A
      cross sectional study was conducted to study the effects of DDT exposure on age
      at menarche and menstrual cycle length among 466 newly married, nulliparous
      female Chinese textile workers aged 20-34 years enrolled between 1996 and 1998.
      Serum was analysed for DDT and its major metabolites. Multivariate linear
      regression was used to estimate DDT exposure effects on age at menarche and
      multivariate logistic regression was used to estimate DDT exposure effects on
      odds of experiencing short or long cycles. RESULTS: Relative to those in the
      lowest DDT quartile, the adjusted mean age at menarche was younger in those in
      the fourth quartile (-1.11 years). Modeled as a continuous variable, a 10 ng/g
      increase in serum DDT concentration was associated with an adjusted reduction in
      age at menarche of 0.20 years. Relative to those in the lowest DDT quartile, odds
      of any short cycle (<21 days) in the previous year were higher for those in the
      fourth quartile (odds ratio = 2.78; 95% CI 1.07 to 7.14). There were no
      associations between serum DDT concentrations and odds of experiencing a long
      cycle (>40 days). CONCLUSION: Results suggest that DDT exposure was associated
      with earlier age at menarche and increased risk of experiencing a shortened
      menstrual cycle.

PMID- 16299098
TI  - The effect of asbestosis on lung cancer risk beyond the dose related effect of
      asbestos alone.
AB  - AIMS: To determine if the presence of asbestosis is a prerequisite for lung
      cancer in subjects with known exposure to blue asbestos (crocidolite). METHODS:
      Former workers and residents of Wittenoom with known amounts of asbestos exposure
      (duration, intensity, and time since first exposure), current chest x ray and
      smoking information, participating in a cancer prevention programme (n = 1988)
      were studied. The first plain chest radiograph taken at the time of recruitment
      into the cancer prevention programme was examined for radiographic evidence of
      asbestosis according to the UICC (ILO) classification. Cox proportional hazards
      modelling was used to relate asbestosis, asbestos exposure, and lung cancer.
      RESULTS: Between 1990 and 2002 there were 58 cases of lung cancer. Thirty six per
      cent of cases had radiographic evidence of asbestosis compared to 12% of study
      participants. Smoking status was the strongest predictor of lung cancer, with
      current smokers (OR = 26.5, 95% CI 3.5 to 198) having the greatest risk.
      Radiographic asbestosis (OR = 1.94, 95% CI 1.09 to 3.46) and asbestos exposure
      (OR = 1.21 per f/ml-year, 95% CI 1.02 to 1.42) were significantly associated with
      an increased risk of lung cancer. There was an increased risk of lung cancer with
      increasing exposure in those without asbestosis. CONCLUSION: In this cohort of
      former workers and residents of Wittenoom, asbestosis is not a mandatory
      precursor for asbestos related lung cancer. These findings support the hypothesis
      that it is the asbestos fibres per se that cause lung cancer, which can develop
      with or without the presence of asbestosis.

PMID- 16299099
TI  - Long driving time is associated with haematological markers of increased
      cardiovascular risk in taxi drivers.
AB  - AIMS: To examine the association between driving time and changes in
      haematological markers of increased risks for cardiovascular diseases (CVD).
      METHODS: The authors conducted a cross sectional analysis of baseline data from
      the Taxi Drivers' Health Study cohort in Taipei, Taiwan. They retrieved
      information on comorbidity, laboratory tests, age, and anthropometric measures
      from medical records of 1157 subjects (mean age 44.6 (SD 8.6) years). Whole blood
      cell (WBC) count was used as the primary haematological marker for increased CVD
      risk, and platelet count and haematocrit as the secondary markers. Standardised
      questionnaires were implemented to collect information on demographics,
      lifestyle, work related physical and psychosocial factors, and driving time
      profiles. Multiple regression was used to estimate the adjusted effects of
      driving time on three haematological markers. RESULTS: The mean measured
      hematological marker was 6656 (SD 1656) cells x10(6)/l for WBC, 47.2 (SD 3.5) %
      for hematocrit, and 243 (SD 52) cells x10(9)/l for platelets. The driving time
      was 264 (SD 76) hours/month. Compared with drivers who drove < or =208
      hours/month (1st quartile cut off), drivers who drove >208 hours/month had a
      higher WBC count (by 317 x10(6)/l; 95% CI 99 to 535), haematocrit (by 0.8%; 95%
      CI 0.3 to 1.2), and platelets (7.9 x10(9)/l; 95% CI 1.0 to 14.8). After adjusting
      for conventional CVD risk factors (age, sex, smoking, hypertension, diabetes, and
      hypercholesterolaemia), obesity, alcohol drinking, regular exercise, and
      sociodemographics (education, marital status, income, and so on), long driving
      time was still associated with significant increases in WBC and platelets,
      whereas the effect on haematocrit was diminished and became statistically non
      significant. Additional controls for physical workload, self-perceived job
      stress, and job dissatisfaction did not alter the associations with increased WBC
      and platelets. CONCLUSIONS: Longitudinal studies are needed to confirm the
      observed cross sectional association and to further examine the specific
      occupational exposures accountable for the association between driving time and
      haematological markers of systemic inflammation and haemostatic alteration.

PMID- 16299101
TI  - World at work: health hazards among foot massage workers in China.

PMID- 16299100
TI  - Does long term residency near industry have an impact on the body burden of
      polychlorinated dibenzo-p-dioxins, furans, and polychlorinated biphenyls in older
      women?
AB  - BACKGROUND: For the retrospective study of environment and health linkages
      biomarkers of exposure are required. Polychlorinated dibenzo-dioxins and furans
      (PCDD/F) and polychlorinated biphenyls (PCBs) have been useful markers in some
      settings. This is the first study of PCDD/F body burden in a population based
      sample from the UK. AIMS AND METHODS: The authors aimed to investigate whether
      long term residents close to a heavy chemical industrial complex (Teesside, UK)
      had a higher body burden and distinct pattern of PCDD/F and PCBs. We measured
      current levels of PCDD/F and PCBs in a population based sample of older women
      (mean 64 years, range 42-79 years). Forty women were recruited, 20 living near
      (zone A: 0.1-2.7 km) and 20 distant (zone C: 5-40 km) from industry during 2000
      03. The authors ascertained occupational exposure to lung carcinogens,
      residential history, consumption of local produce, breast feeding, diet, and
      height and weight. RESULTS: The mean body burden measured on lipid basis in ng/kg
      for the whole sample was: WHO-TEQ (PCDD/Fs): 29.9, 2378TCDD: 4.0, PCB 118:16200,
      PCB156: 13100. Body burdens were similar to others reported from industrialised
      countries, except that mean 2378TCDD was slightly higher. Mean ages, body mass
      index, and lifelong dietary patterns were similar in both zones. The authors
      found no significant difference in mean body burden levels between zones A and C
      before or after adjustment for covariates. All congener patterns were consistent
      with an urban background pattern, and there was no significant difference between
      congener compositions in the two zones. The TCDD body burden increased with age
      with accelerated increments above age 70. CONCLUSION: Long term residency near
      heavy and chemical industry did not have an effect on women's body burden of
      PCDD/Fs and PCBs on Teesside, UK. The body burden of PCDD/F and PCBs was not a
      suitable biomarker for chronic, non-occupational exposure to industrial air
      pollution.

PMID- 16299102
TI  - Health impact assessment.

PMID- 16299103
TI  - Myosin light chain kinase and myosin phosphorylation effect frequency-dependent
      potentiation of skeletal muscle contraction.
AB  - Repetitive stimulation potentiates contractile tension of fast-twitch skeletal
      muscle. We examined the role of myosin regulatory light chain (RLC)
      phosphorylation in this physiological response by ablating Ca(2+)/calmodulin
      dependent skeletal muscle myosin light chain kinase (MLCK) gene expression.
      Western blot and quantitative-PCR showed that MLCK is expressed predominantly in
      fast-twitch skeletal muscle fibers with insignificant amounts in heart and smooth
      muscle. In contrast, smooth muscle MLCK had a more ubiquitous tissue
      distribution, with the greatest expression observed in smooth muscle tissue.
      Ablation of the MYLK2 gene in mice resulted in loss of skeletal muscle MLCK
      expression, with no change in smooth muscle MLCK expression. In isolated fast
      twitch skeletal muscles from these knockout mice, there was no significant
      increase in RLC phosphorylation in response to repetitive electrical stimulation.
      Furthermore, isometric twitch-tension potentiation after a brief tetanus
      (posttetanic twitch potentiation) or low-frequency twitch potentiation
      (staircase) was attenuated relative to responses in muscles from wild-type mice.
      Interestingly, the site of phosphorylation of the small amount of
      monophosphorylated RLC in the knockout mice was the same site phosphorylated by
      MLCK, indicating a potential alternative signaling pathway affecting contractile
      potentiation. Loss of skeletal muscle MLCK expression had no effect on cardiac
      RLC phosphorylation. These results identify myosin light chain phosphorylation by
      the dedicated skeletal muscle Ca(2+)/calmodulin-dependent MLCK as a primary
      biochemical mechanism for tension potentiation due to repetitive stimulation in
      fast-twitch skeletal muscle.

PMID- 16299104
TI  - The expression of the pituitary growth hormone-releasing hormone receptor and its
      splice variants in normal and neoplastic human tissues.
AB  - Various attempts to detect human pituitary growth hormone-releasing hormone
      receptor (pGHRH-R) in neoplastic extrapituitary tissues have thus far failed.
      Recently, four splice variants (SVs) of GHRH-R have been described, of which SV1
      has the highest structural homology to pGHRH-R and likely plays a role in tumor
      growth. The aim of this study was to reinvestigate whether human tumors and
      normal human extrapituitary tissues express the pGHRH-R and to corroborate our
      previous findings on its SVs. Thus, we developed a real-time PCR method for the
      detection of the mRNA for the pGHRH-R, its SVs, and the GHRH peptide. Using real
      time PCR, Western blotting, and radioligand-binding assays, we detected the mRNA
      for pGHRH-R and pGHRH-R protein in various human cancer cell lines grown in nude
      mice and in surgical specimens of human lung cancers. The expression of mRNA for
      SVs of pGHRH-R and GHRH was likewise found in xenografts of human non-Hodgkin's
      lymphomas, pancreatic cancer, glioblastoma, small-cell lung carcinomas, and in
      human nonmalignant prostate, liver, lung, kidney, and pituitary. Western blots
      showed that these normal and malignant human tissues contain SV1 protein and
      immunoreactive GHRH. Our results demonstrate that some normal human tissues and
      tumors express mRNA and protein for the pGHRH-R and its splice variants. These
      findings confirm and extend the concept that GHRH and its receptors play an
      important role in the pathophysiology of human cancers.

PMID- 16299106
TI  - Different effects of stress on alcohol drinking behaviour in male and female mice
      selectively bred for high alcohol preference.
AB  - AIMS: The purpose of the present study was to examine the effects of stress on
      alcohol drinking behaviour in male and female mice with a genetic predisposition
      toward high alcohol preference (HAP2 line). METHODS: Alcohol-naive male (n = 22)
      and female (n = 23) HAP2 mice were assigned to a restraint stress or no stress
      control group. Stress was initially applied for 2 h per day on 10 consecutive
      days. All mice were then given daily 2 h limited-access to a 10% v/v alcohol
      solution or water, with food freely available, for 21 days. Over the next 20
      days, 2 h restraint stress was applied every other day immediately prior to 2 h
      access to alcohol and water. On intervening days, all mice received 2 h access to
      alcohol and water in the absence of stress. Following this phase of the study,
      the effects of restraint stress on acoustic startle reactivity was assessed in
      all mice. Finally, all mice were given continuous access to alcohol and water for
      8 days. RESULTS: Ten days of prior stress exposure did not significantly alter
      the acquisition of limited-access alcohol drinking. Subsequent exposures to
      intermittent restraint stress produced subtle but consistent effects on alcohol
      intake that differed in males vs females: stress increased alcohol intake in
      males and decreased alcohol intake in females. Restraint stress did not alter
      acoustic startle reactivity. Under continuous-access conditions after stress
      termination, the stress-induced increase in alcohol intake in males became more
      robust; however, in females, alcohol intake returned to the control group level.
      CONCLUSIONS: These findings suggest that the effects of stress on alcohol
      drinking in mice with a genetic predisposition toward high alcohol preference
      depend on sex.

PMID- 16299107
TI  - A possible way to motivate ambivalent patients to undergo detoxification.

PMID- 16299105
TI  - Experience induces structural and biochemical changes in the adult primate brain.
AB  - Primates exhibit complex social and cognitive behavior in the wild. In the
      laboratory, however, the expression of their behavior is usually limited. A large
      body of literature shows that living in an enriched environment alters dendrites
      and synapses in the brains of adult rodents. To date, no studies have
      investigated the influence of living in a complex environment on brain structure
      in adult primates. We assessed dendritic architecture, dendritic spines, and
      synaptic proteins in adult marmosets housed in either a standard laboratory cage
      or in one of two differentially complex habitats. A month-long stay in either
      complex environment enhanced the length and complexity of the dendritic tree and
      increased dendritic spine density and synaptic protein levels in the hippocampus
      and prefrontal cortex. No differences were detected between the brains of
      marmosets living in the two differentially complex environments. Our results show
      that the structure of the adult primate brain remains highly sensitive even to
      modest levels of experiential complexity. For adult primates, living in standard
      laboratory housing may induce reversible dendritic spine and synapse decreases in
      brain regions important for cognition.

PMID- 16299108
TI  - Worldwide alcohol-related research and the disease burden.
AB  - AIMS: The purpose of this study was to determine the international commitment to
      alcohol-related research relative to its global burden of disease, which is 4% of
      disability adjusted life years (DALYs). METHODS: The worldwide literature indexed
      in the Science Citation Index and the Social Sciences Citation Index during 1992
      2003 was analysed using advanced bibliometric techniques. RESULTS: Biomedical
      research and the global disease burden due to alcohol both increased during 1992
      2003, whilst the number of papers from alcohol-related research remained static
      and declined to <0.7% of all biomedical research literature. Nearly 58% of all
      alcohol-related research papers were from Canada and the United States, 30% from
      Western Europe, and 10% from Australia, New Zealand, or Japan. However, these
      regions suffer only 13% of the global burden of disease due to alcohol;
      meanwhile, the rest of the world contributed only 8% of the total research whilst
      suffering from 87% of the disease burden. The estimated annual expenditure on
      alcohol-related research in 2001 was 730 million dollars, or about 12 dollars per
      DALY due to alcohol. CONCLUSIONS: The global commitment to alcohol-related
      research is only one-sixth of that warranted by the burden of disease due to
      alcohol. Most such research is conducted in the developed world but is still less
      than that appropriate to the regional burden of disease. There is a need for more
      interest in alcohol-related research in the developing world, particularly in
      Latin America and Eastern Europe in view of their high burden of disease due to
      alcohol.

PMID- 16299109
TI  - The role of alcohol expectancy and drinking refusal self-efficacy beliefs in
      university student drinking.
AB  - AIMS: University student alcohol misuse is a considerable problem. Alcohol
      expectancy research has contributed significantly to our understanding of problem
      drinking in young adults. Most of this research has investigated positive
      expectancy alone. The current study utilized two measures of alcohol expectancy,
      the alcohol expectancy questionnaire (AEQ) and the drinking expectancy profile
      [consisting of the drinking expectancy questionnaire (DEQ) and the drinking
      refusal self-efficacy questionnaire] to predict severity of alcohol dependence,
      frequency of drinking, and the quantity of alcohol consumed per occasion.
      METHODS: Measures of drinking behaviour and alcohol expectancy were completed by
      174 undergraduate university students. RESULTS: Positive alcohol expectancy
      factors accounted for significant variance in all three drinking indices, with
      the DEQ adding additional variance to AEQ scores on frequency and severity of
      alcohol dependence indices. Negative expectancy did not add incremental variance
      to the prediction of drinking behaviour in this sample. Drinking refusal self
      efficacy and dependence beliefs added additional variance over positive and
      negative expectancies in the prediction of all three drinking parameters.
      CONCLUSIONS: Positive expectancy and drinking refusal self-efficacy were strongly
      related to university student drinking. The incorporation of expectancy as a
      means of informing prevention approaches in tertiary education shows promise.

PMID- 16299110
TI  - Inhaled corticosteroids in COPD: a light at the end of the tunnel?

PMID- 16299111
TI  - Non-invasive mechanical ventilation: when to start for what benefit?

PMID- 16299112
TI  - Improving survival in idiopathic pulmonary arterial hypertension: revisiting the
      "kingdom of the near-dead".

PMID- 16299113
TI  - Pulmonary hypertension after splenectomy: a consequence of loss of the splenic
      filter or is there something more?

PMID- 16299120
TI  - Tension pneumothorax complicating autologous "blood patch" pleurodesis.
AB  - Autologous "blood patching" has been used successfully for the treatment of
      persistent air leak in patients with spontaneous secondary pneumothorax. The case
      history is presented of a 19 year old woman with cystic fibrosis who developed
      tension pneumothorax following this procedure, with rapid clinical deterioration
      until the obstruction was cleared. To avoid this potentially fatal complication
      we recommend that "blood patch" pleurodesis be performed only through large bore
      intercostal catheters, that blood is rapidly transferred into the catheter
      tubing, a sterile saline flush and full resuscitation equipment is available, and
      the operator is skilled in the management of tension pneumothorax.

PMID- 16299118
TI  - Randomised controlled trial of non-invasive ventilation (NIV) for nocturnal
      hypoventilation in neuromuscular and chest wall disease patients with daytime
      normocapnia.
AB  - BACKGROUND: Long term non-invasive ventilation (NIV) reduces morbidity and
      mortality in patients with neuromuscular and chest wall disease with hypercapnic
      ventilatory failure, but preventive use has not produced benefit in normocapnic
      patients with Duchenne muscular dystrophy. Individuals with nocturnal hypercapnia
      but daytime normocapnia were randomised to a control group or nocturnal NIV to
      examine whether nocturnal hypoventilation is a valid indication for NIV. METHODS:
      Forty eight patients with congenital neuromuscular or chest wall disease aged 7
      51 years and vital capacity<50% predicted underwent overnight respiratory
      monitoring. Twenty six with daytime normocapnia and nocturnal hypercapnia were
      randomised to either nocturnal NIV or to a control group without ventilatory
      support. NIV was started in the control group if patients fulfilled preset safety
      criteria. RESULTS: Peak nocturnal transcutaneous carbon dioxide tension (Tcco2)
      did not differ between the groups, but the mean (SD) percentage of the night
      during which Tcco2 was >6.5 kPa decreased in the NIV group (-57.7 (26.1)%) but
      not in controls (-11.75 (46.1)%; p=0.049, 95% CI -91.5 to -0.35). Mean (SD)
      arterial oxygen saturation increased in the NIV group (+2.97 (2.57)%) but not in
      controls (-1.12 (2.02)%; p=0.024, 95% CI 0.69 to 7.5). Nine of the 10 controls
      failed non-intervention by fulfilling criteria to initiate NIV after a mean (SD)
      of 8.3 (7.3) months. CONCLUSION: Patients with neuromuscular disease with
      nocturnal hypoventilation are likely to deteriorate with the development of
      daytime hypercapnia and/or progressive symptoms within 2 years and may benefit
      from the introduction of nocturnal NIV before daytime hypercapnia ensues.

PMID- 16299121
TI  - Home nebulisers can affect the colour of domestic gas flames.

PMID- 16299122
TI  - Commentary: about that measurement problem.

PMID- 16299123
TI  - Measles outbreak in the Republic of the Marshall Islands, 2003.
AB  - BACKGROUND: Measles is a highly contagious viral infection. Measles transmission
      can be prevented through high population immunity (>or=95%) achieved by measles
      vaccination. In the Republic of the Marshall Islands (RMI), no measles cases were
      reported during 1989-2002; however, a large measles outbreak occurred in 2003.
      Reported 1-dose measles vaccine coverage among children aged 12-23 months varied
      widely (52-94%) between 1990 and 2000. METHODS: RMI is a Pacific island nation
      (1999 population: 50,840). A measles case was defined as fever, rash, and cough,
      or coryza, or conjunctivitis, in an RMI resident between July 13 and November 7,
      2003. A vaccination campaign was used for outbreak control. RESULTS: Of the 826
      reported measles cases, 766 (92%) occurred in the capital (Majuro). There were
      186 (23%) cases in infants aged <1 year and 309 (37%) of cases in persons aged
      >or=15 years. The attack rate was highest among infants (Majuro atoll: 213
      cases/1,000 infants). Among cases aged 1-14 years, 281 (59%) reported no measles
      vaccination before July 2003. There were 100 hospitalizations and 3 deaths. The
      measles H1 genotype was identified. The vaccination campaign resulted in 93%
      coverage among persons aged 6 months to 40 years. Interpretation Populations
      without endemic measles transmission can accumulate substantial susceptibility
      and be at risk for large outbreaks when measles virus is imported. 'Islands' of
      measles susceptibility may develop in infants, adults, and any groups with low
      vaccine coverage. To prevent outbreaks, high population immunity must be
      sustained by maintaining and documenting high vaccine coverage.

PMID- 16299124
TI  - Intermittent exotropia increasing with near fixation: a "soft" sign of
      neurological disease.
AB  - AIM: To examine the association of distance-near disparity with neurological
      disease in children with intermittent exotropia. METHODS: A retrospective
      analysis was performed of the medical records of all children with intermittent
      exotropia examined at the Arkansas Children's Hospital between 1989 and 2002. The
      study group consisted of children with intermittent exotropia who had a near
      deviation that exceeded the deviation at distance by at least 10 prism dioptres.
      The control group consisted of children with intermittent exotropia who had a
      distance deviation greater than or equal to the deviation at near. The main
      outcome measures were the prevalence of neurological abnormalities in the study
      and control groups. RESULTS: Among the 29 patients in the study group, 19 (66%)
      had a history of concurrent neurological abnormalities. Associated neurological
      conditions included developmental delay (10 patients), attention deficit disorder
      (four patients), cerebral palsy (four patients), history of intracranial
      haemorrhage (four patients), periventricular leucomalacia (three patients),
      seizures (two patients), cortical visual impairment (two patients), hydrocephalus
      (one patient), history of anoxic brain damage (one patient), history of
      encephalitis (one patient), and autism (one patient). Among the 37 patients in
      the control group, seven (19%) had a history of concurrent neurological
      abnormalities. The difference in the prevalence of neurological disease between
      the study group and the control group was significant (p = 0.0002). CONCLUSION:
      Intermittent exotropia increasing with near fixation is associated with
      neurological disease in children.

PMID- 16299125
TI  - ROP and neurodevelopmental disabilities.

PMID- 16299126
TI  - Overcoming the technical challenges of deep lamellar keratoplasty.

PMID- 16299127
TI  - Mouse models may provide new insight into the relation between cholesterol and
      age related macular degeneration.

PMID- 16299128
TI  - Characteristic clinical features as an aid to the diagnosis of suppurative
      keratitis caused by filamentous fungi.
AB  - AIM: To assess whether the presence of characteristic clinical features can be
      used as a diagnostic aid for suppurative keratitis caused by filamentous fungi.
      METHODS: Patients presenting with suppurative keratitis in India underwent
      detailed clinical examination followed by microbiological investigation of
      corneal scrapes. A partial diagnostic score based upon the strength of the
      association, as estimated by the odds ratio, between reported clinical features
      and laboratory confirmed diagnoses was devised and subsequently tested using a
      case series from Ghana. RESULTS: Serrated margins, raised slough, dry texture,
      satellite lesions and coloration other than yellow occurred more frequently in
      cases of filamentous fungal keratitis than bacterial keratitis (p<0.05). Hypopyon
      and fibrinous exudate were observed more frequently in bacterial keratitis
      (p<0.05). When incorporated into a backwards stepwise logisitic regression model
      only serrated margins, raised slough, and colour were independently associated
      with fungal keratitis; these features were used in the scoring system. The
      probability of fungal infection if one clinical feature was present was 63%,
      increasing to 83% if all three features were present. CONCLUSIONS:
      Microbiological investigations should be performed whenever possible; however,
      where facilities are not available, a rapid presumptive diagnosis of suppurative
      keratitis may be possible by scoring clinical features.

PMID- 16299130
TI  - "Near misses" in a cataract theatre: how do we improve understanding and
      documentation?
AB  - AIM: Near miss event reporting is widely used in industry to highlight
      potentially unsafe areas or practice. The aim of this study was to see if a
      descriptive method of recording near misses was an appropriate method for use in
      an ophthalmic operating theatre and to quantify how many untoward events were
      recorded using this system. METHODS: The study was wholly conducted in a cataract
      theatre in the United Kingdom. The theatre nurse assigned to the patient in their
      journey through the operating theatre was asked to note any untoward events. As,
      at present, there is no consensus definition of near misses in ophthalmology the
      nurses recorded, in free text, any events that they considered to be a deviation
      from the normal routine in that theatre. RESULTS: Of the 500 cases randomly
      chosen, 96 "deviations from normal routine" were described in 93 patients-that
      is, 19% of cases. All forms distributed to the nurses were returned (100%
      response rate). The commonest abnormal events were intraoperative (69), with a
      lesser number being recorded preoperatively (27). When these events were further
      classified, it was thought that 25 could be classified as near misses. One true
      adverse event was recorded during the study. CONCLUSIONS: The results suggest
      that experienced nursing staff in an ophthalmic theatre are a reliable source for
      collecting data regarding near misses. A consensus is now required to define near
      misses in ophthalmology and to devise a user friendly input system that can use
      these definitions to consistently record these potentially vital events.

PMID- 16299129
TI  - A population based survey of the prevalence and types of glaucoma in rural West
      Bengal: the West Bengal Glaucoma Study.
AB  - AIM: To determine (i) the prevalence of glaucoma in people aged > or =50 years,
      (ii) the proportions of different types of glaucoma, (iii) the distributions of
      intraocular pressure and vertical cup disc ratio. METHOD: Population based
      prevalence survey in rural West Bengal. People aged > or =50 years in randomly
      selected villages in 24 Parganas South district. The main outcome measures were
      diagnosis of glaucoma, based on criteria described by the International Society
      for Geographic and Epidemiological Ophthalmology. RESULTS: 1594 people aged > or
      =50 years were enumerated in nine villages; 1324 (83.1%) were surveyed and 1269
      people adequately examined. 42 definite cases of glaucoma were identified, with
      prevalence increasing from 2.7% (95% CI 1.7 to 3.7) in people aged 50-59 years to
      6.5% (95% CI 0.0 to 14.1) in those aged > or =80 years. The age standardised
      estimate for the prevalence of all glaucoma in people aged > or =50 years was
      3.4%. Only three cases of primary angle closure glaucoma (PACG) were identified,
      giving a crude ratio of primary open angle glaucoma (POAG) to PACG of more than
      10:1. Three people with glaucoma were blind in one eye but none was blind in both
      eyes. CONCLUSION: Compared to other surveys of glaucoma in India, the age
      standardised prevalence observed was less than in Hyderabad, but similar to Tamil
      Nadu and Dhaka. The ratio of POAG to PACG was much higher than found previously,
      suggesting that PACG may be less prevalent in Bengalis than in Indian populations
      living in south India. The authors conclude that ophthalmic services in West
      Bengal should focus on detecting POAG. Since there is still no satisfactory
      method of screening for POAG, there is no alternative to case detection
      (opportunistic screening) in eye clinics.

PMID- 16299131
TI  - Effect of cataract extraction on frequency doubling technology perimetry in
      patients with glaucoma.
AB  - AIM: To evaluate the effect of cataract surgery on frequency doubling technology
      (FDT) perimetry in patients with co-existing cataract and glaucoma. METHODS: In
      this consecutive prospective cohort study 27 patients with open angle glaucoma
      scheduled for cataract extraction alone or combined with trabeculectomy were
      enrolled. All patients underwent FDT threshold C-20 visual fields within 3 months
      before and 3 months after surgery. Changes in mean deviation (MD) and pattern
      standard deviation (PSD) were evaluated. Additionally, changes in best corrected
      logMAR visual acuity (VA), intraocular pressure (IOP), and number of glaucoma
      medications were also studied. RESULTS: 22 patients completed the study. VA
      improved after surgery, from 0.47 (SD 0.19) to 0.12 (0.17) (p<0.001). The visual
      indexes changed after cataract extraction: MD improved (from -10.9 (SD 4.6) dB to
      -7.0 (4.6) dB; p<0.001) while PSD worsened (from 7.1 (SD 3.5) dB to 8.5 (3.8) dB;
      p = 0.001). CONCLUSION: In patients with co-existing cataract and glaucoma,
      examined with FDT, MD improved and PSD worsened after cataract surgery. Global
      indexes of FDT should be interpreted with caution in patients with glaucoma and
      cataracts.

PMID- 16299132
TI  - The relative effects of corneal thickness and age on Goldmann applanation
      tonometry and dynamic contour tonometry.
AB  - AIMS: To establish the effects of central corneal thickness (CCT) on intraocular
      pressure (IOP) measured with a prototype Pascal dynamic contour tonometer (DCT),
      to evaluate the effect of CCT and age on the agreement between IOP measured with
      the Pascal DCT and Goldmann applanation tonometer (GAT), and to compare the
      interobserver and intraobserver variation of the DCT with the GAT. METHODS: GAT
      and DCT IOP measurements were made on 130 eyes of 130 patients and agreement was
      assessed by means of Bland-Altman plots. The effect of CCT and age on GAT/DCT IOP
      differences was assessed by linear regression analysis. Interobserver and
      intraobserver variations for GAT and DCT were assessed in 100 eyes of 100
      patients. RESULTS: The mean difference (95% limits of agreement) between GAT and
      DCT was -0.7 (-6.3 to 4.9) mm Hg. GAT/DCT IOP differences increased with thicker
      CCT (slope 0.017 mm Hg/microm, 95% CI 0.004 to 0.03, r2 = 0.05, p = 0.01), and
      with greater age, slope 0.05 mm Hg/year (95% CI 0.012 to 0.084, r2 = 0.05, p =
      0.01). The intraobserver variability of GAT and DCT was 1.7 mm Hg and 3.2 mm Hg,
      respectively. The interobserver variability was (mean difference (95% limits of
      agreement)) 0.4 (-3.5 to 4.2) mm Hg for GAT and 0.2 (-4.9 to 5.3) mm Hg for DCT.
      CONCLUSIONS: GAT is significantly more affected than DCT by both CCT and subject
      age. The effect of age suggests an age related corneal biomechanical change that
      may induce measurement error additional to that of CCT. The prototype DCT has
      greater measurement variability than the GAT.

PMID- 16299133
TI  - Aniseikonia associated with epiretinal membranes.
AB  - AIMS: To determine whether the computerised version of the new aniseikonia test
      (NAT) is a valid, reliable method to measure aniseikonia and establish whether
      aniseikonia occurs in patients with epiretinal membranes (ERM) with preserved
      good visual acuity. METHODS: With a computerised version of the NAT, horizontal
      and vertical aniseikonia was measured in 16 individuals (mean 47 (SD 16.46)
      years) with no ocular history and 14 patients (mean 67.7 (14.36) years) with ERM.
      Test validity was evaluated by inducing aniseikonia with size lenses. Test
      reliability was assessed by the test-retest method. RESULTS: In normal
      individuals, the mean percentage (SD) aniseikonia was -0.24% (0.71) horizontal
      and 0% (0.59) vertical. Validity studies revealed mean (SD) 0.990 (0.005)
      horizontal and 0.991 (0.004) vertical correlation coefficients, 0.985 (0.111)
      horizontal and 0.989 (0.102) vertical slope. Repeatability coefficients were 1.04
      horizontal and 0.88 vertical. Aniseikonia in patients with ERM ranged from 4% to
      14%. Eight patients showed 2% or more size difference between horizontal and
      vertical meridians. CONCLUSIONS: The aniseikonia test used in this study can be
      considered a simple, fast, valid and reliable method to measure the difference in
      image size perceived by each eye. Aniseikonia does occur in symptomatic patients
      with ERM. The effect of ERM on image size is heterogeneous across the retinal
      area affected.

PMID- 16299134
TI  - Comparison of optical coherence tomography models OCT1 and Stratus OCT for
      macular retinal thickness measurement.
AB  - AIMS: To compare the values measured for retinal macular thickness with the first
      and last generations of the optical coherence tomograph (OCT1 and Stratus OCT,
      Zeiss, Humphrey Division). METHODS: This was a cohort study. 59 eyes were
      examined: 17 had a normal macula and 42 had a diabetic macular oedema. In each
      eye, mean retinal thickness (RT) was measured automatically in the nine macular
      Early Treatment Diabetic Retinopathy Study areas and at the foveal centre, using
      OCT1 and Stratus OCT. The paired mean RT values for each area and the type and
      proportion of artefacts were compared. RESULTS: Of the 590 automatic
      measurements, 505 had no artefact, either with OCT1 or Stratus OCT. The mean
      difference between the OCT1 and Stratus OCT measurements was 25 (SD 26.2) microm
      (p<0.0001). With Stratus OCT, RT values were significantly higher, by 8.1%
      (7.8%), than with OCT1. Artefacts were only observed in cases of diabetic macular
      oedema and were significantly more frequent with OCT1 than Stratus OCT (10.5%
      versus 4.4, p<0.0001). CONCLUSION: The macular retinal thickness values measured
      with Stratus OCT were significantly higher than those measured with OCT1. Stratus
      OCT has the advantage of producing fewer artefacts than OCT1 in pathological
      cases.

PMID- 16299136
TI  - Development of Microelectromechanical Systems (MEMS) forceps for intraocular
      surgery.
AB  - AIM: To develop silicon microforceps for intraocular surgery using
      Microelectromechanical Systems (MEMS) technology, the application of microchip
      fabrication techniques for the production of controllable three dimensional
      devices on the micrometre scale. METHODS: Prototype MEMS forceps were designed
      and manufactured for intraocular surgery. Scanning electron microscopy was used
      to evaluate device tip construction. Designs using both thermal expansion
      actuators and conventional mechanical activation were tested in human cadaver
      eyes and in vivo rabbit eyes to assess functionality in standard vitreoretinal
      surgery. RESULTS: MEMS forceps were constructed with various tip designs ranging
      from 100 mum to 2 mm in length. Scanning electron microscopy confirmed accurate
      construction of micro features such as forceps teeth as small as tens of
      micrometres. In surgical testing, the silicon forceps tips were effective in
      surgical manoeuvres, including grasping retinal membranes and excising tissue.
      The mechanical actuator design on a 20 gauge handle was more operational in the
      intraocular environment than the thermal expansion actuator design. While
      handheld operation was possible, the precision of the forceps was best exploited
      when mounted on a three axis micromanipulator. CONCLUSION: MEMS microforceps are
      feasible for conventional vitreoretinal surgery, and offer advances in terms of
      small scale, operating precision, and construction tolerance.

PMID- 16299137
TI  - Is routine biopsy of the lacrimal sac wall indicated at dacryocystorhinostomy? A
      prospective study and literature review.
AB  - OBJECTIVE: To determine whether routine biopsy of the lacrimal sac wall at
      dacryocystorhinostomy (DCR) is indicated. METHODS: A prospective study and
      literature review. In 193 consecutive endoscopic DCRs performed on 164 patients
      (108 females and 56 males) part of the medial wall of the lacrimal sac was sent
      for histological examination. The mean age of the patients was 64 years with a
      range of 2.5-89 years. Previous reported series were reviewed. RESULTS: Of the
      193 specimens, 44 (23%) showed normal histology, 146 (76%) showed varying degrees
      of non-specific chronic inflammation, and three (1.2%) showed specific pathology.
      Of the three specimens that showed specific pathology two showed sarcoidosis and
      one showed transitional cell papilloma. The two specimens with sarcoidosis were
      obtained from one patient who underwent bilateral surgery. In this and the six
      previous reported series only seven of 1294 specimens (0.5%) showed specific
      pathology, which was definitely not suspected preoperatively or intraoperatively,
      and only one of these (0.08%) was found to be malignant (a lymphoma).
      CONCLUSIONS: Biopsy of the lacrimal sac wall at DCR is not indicated routinely
      and is only indicated if there is a reason to suspect pathology other than
      chronic inflammation preoperatively or intraoperatively.

PMID- 16299138
TI  - Variation in rates of severe retinopathy of prematurity among neonatal intensive
      care units in the Australian and New Zealand Neonatal Network.
AB  - AIM: To analyse variations in rates of severe retinopathy of prematurity (ROP)
      among neonatal intensive care units (NICUs) in the Australian and New Zealand
      Neonatal Network (ANZNN), adjusting for sampling variability and for case mix.
      METHODS: 25 NICUs were included in the study of 2105 infants born at less than 29
      weeks in 1998 and 1999, who survived to 36 weeks post-menstrual age and were
      examined for ROP. The observed NICU rates of severe ROP were adjusted for case
      mix using logistic regression on gestation, weight for gestational age and sex,
      and for sampling variability using shrinkage estimates. The corrected rate in the
      best 20% of NICUs was identified and NICU variations in rates were compared with
      those in 2000-1. RESULTS: The overall (unadjusted) rate of severe ROP in the
      NICUs was 9.6% (interquartile range 5.4-12.8%). After adjusting for both case mix
      and sampling variability there remained significant variation among the NICUs.
      20% of NICUs had a rate of severe ROP </=5.9%. Variation in rates among NICUs
      showed a similar pattern in both time periods. If the overall network rate was
      reduced to 5.9%, the 20th centile of the adjusted rates, there would be 79 fewer
      cases in a 2 year period, in contrast with 26 fewer if rates in the two units
      with excess rates improved to the average. CONCLUSIONS: Considerable variation in
      rates of severe ROP among NICUs remained after adjustment for case mix and
      sampling variability. These data will facilitate investigation of potentially
      better practices associated with a reduced risk of severe ROP.

PMID- 16299139
TI  - Deep lamellar keratoplasty by deep parenchyma detachment from the corneal limbs.
AB  - AIM: To improve the deep lamellar keratoplasty technique. METHOD: For the easy
      and reliable perfomance of deep lamellar keratoplasty (DLKP), detachment of
      Descemet's membrane through the corneal limber flap was improved. To expose
      Descemet's membrane, the parenchyma was detached by hydrodelamination through a
      sclerocorneal flap made in the corneal limbs. The parenchyma was removed after
      the pseudochamber between it and Descemet's membrane was maintained with
      viscoelastic material. The corneal graft was placed with a running suture. 22
      eyes were treated. RESULTS: Complete exposure of Descemet's membrane was obtained
      in 20 of the 22 eyes (91%). The membrane was perforated in five of the 22 eyes
      (23%) during surgery, and two of the 22 eyes (9%) were converted to penetrating
      keratoplasty. These two eyes developed keratoconus after acute corneal hydrops.
      CONCLUSION: Compared with the conventional procedure, this new method provides
      easy, reliable exposure of Descemet's membrane.

PMID- 16299140
TI  - Contact lenses and special back surface design after penetrating keratoplasty to
      improve contact lens fit and visual outcome.
AB  - AIMS: To describe the fitting of patients with high or irregular astigmatism
      following penetrating keratoplasty with contact lenses and to answer the question
      whether or not contact lenses with special back surface design can improve visual
      acuity in complex cases after penetrating keratoplasty. METHODS: 28 eyes were
      included. They were fitted with contact lenses with a special back surface that
      was designed for optical rehabilitation after penetrating keratoplasty. Four
      different types of these lenses (tricurve, keratoconus, reverse, oblong) were
      used selectively depending on abnormal eccentricity determined by
      videokeratoscope. The patients were followed up for an average period of 15.5
      months. Lens tolerance and corrected visual acuity were evaluated and compared
      with that corrected with spectacles. RESULTS: The visual acuity was significantly
      improved in nearly all eyes with an average increase of 3.6 lines (maximal nine
      lines) accompanied by good contact lens tolerance and satisfactory contact lens
      fit. No noticeable complications were observed. CONCLUSION: Contact lenses with
      special back surface design can improve visual results and lens tolerance, and
      minimise problems in contact lens fitting. This is in favour of contact lenses as
      an alternative to surgical procedures for correction of high or irregular
      astigmatism after penetrating keratoplasty. This procedure is recommended
      especially in cases of patients who decline further operative interventions.

PMID- 16299141
TI  - Lower limits of fluorescein and indocyanine green dye for digital cSLO
      fluorescence angiography.
AB  - BACKGROUND: With the advent of digital confocal scanning laser ophthalmoscopy it
      is possible to detect low levels of fluorescence. Here we used a novel confocal
      scanning laser ophthalmoscope (cSLO) to determine lower limits of dye required
      for fluorescein (FL) and indocyanine green (ICG) angiography. METHODS: A cSLO
      (Heidelberg retina angiograph 2, Heidelberg Engineering, Dossenheim, Germany)
      with an optically pumped solid state laser (488 nm) for FL and a diode laser (790
      nm) for ICG angiography (FL/ICG-A) was used. 62 FL-As were performed in 53
      patients and 45 ICG-As were performed in 39 patients with neovascular age related
      macular degeneration. The volume and overall dye content of bolus injections was
      gradually tapered (FL: 500 mg, 250 mg, 200 mg, 166 mg, 100 mg; ICG: 25 mg, 20 mg,
      15 mg, 10 mg, 5 mg, 2.5 mg), while dye concentrations were kept constant at 100
      mg/ml for FL and at 5 mg/ml for ICG. Images were obtained 1, 5, 15, and 30
      minutes after dye injection. Image quality was evaluated by two independent
      readers using standardised criteria. RESULTS: For amounts down to 166 mg for FL
      and to 5 mg for ICG, sufficient image quality was achieved during all phases
      following injection. Only late phase images showed less contrast compared to
      typically used dye amounts, which was irrelevant for interpretation and clinical
      management. CONCLUSIONS: With the increased sensitivity of this novel cSLO
      system, amounts of injected dye during FL-A can be reduced to one third for FL
      and to one fifth for ICG without relevant loss of image quality or information
      compared to conventionally used dye levels. These amounts can be used for routine
      angiography and allow relevant savings for units performing FL-A.

PMID- 16299142
TI  - Systemic carboplatin for retinoblastoma: change in tumour size over time.
AB  - BACKGROUND/AIM: Chemotherapy for intraocular retinoblastoma is used to shrink
      individual retinal tumours to a size amenable to focal treatments. Quantitative
      data regarding retinal tumour response following treatment with primary systemic
      carboplatin are reported. METHODS: Changes in area and largest basal diameter of
      tumours that were exposed to carboplatin, had no concomitant focal treatment, and
      had digital funduscopic photography performed before and after treatment, were
      measured. Response was evaluated. RESULTS: 36 tumours were measured following one
      treatment: 34/36 (94.4%) responded, with a 37.1% mean decrease in area (median =
      37.0%; range 4.0%-76.7%). Mean reduction in basal diameter was 21.3% (med =
      21.0%; -7.9%-52.5%). 20 tumours were treated with a second cycle: 15/20 (75.0%)
      responded. Mean decrease in area was 17.8% (med = 15.3%; -7.0%-49.7%). The mean
      cumulative decrease in area after two treatments was 55.1% (med = 56.2%; 33.0%
      74.5%). Mean cumulative reduction in basal diameter was 33.6% (med = 33.6%; 10.9%
      53.2%). 12 tumours were treated with a third cycle: 3/12 (25.0%) responded, 8/12
      were stable, and one progressed. Mean decrease in area was 5.4% (med = 7.2%; 
      17.7%-20.6%). Cumulative decrease in area after three treatments was 58.1% (med =
      57.3%; 34.8%-77.2%). Mean cumulative reduction in basal diameter was 38.8% (med =
      38.2%; 19.1%-54.1%). CONCLUSIONS: Carboplatin caused measurable shrinkage of
      retinoblastoma tumours. Response was greatest following the initial treatment and
      decreased with subsequent treatments.

PMID- 16299144
TI  - Increased expression of vascular endothelial growth factor associated with
      accumulation of lipids in Bruch's membrane of LDL receptor knockout mice.
AB  - AIM: To investigate the pathogenesis of age related macular degeneration (ARM)
      with respect to lipid accumulation within Bruch's membrane (BrM) in a knockout
      model with low density lipoprotein (LDL) receptor deficiency. METHODS: LDL
      receptor deficient mice and C57BL/6 controls were fed a standard diet or a high
      fat (HF) diet. Plasma total cholesterol (pTC) was determined. Eyes were examined
      by transmission electron microscopy. Immunohistochemical staining for VEGF was
      performed. RESULTS: pTC were highest in LDL receptor deficient mice after HF diet
      and elevated after standard diet compared to controls with and without HF diet.
      While BrM of controls did not exhibit any visible changes, membrane bound
      translucent particles were seen in all BrM of knockout mice. The amount of these
      particles was substantially increased and membranes were thickened after HF diet.
      VEGF staining was positive in knockout mice only and was located in retinal
      pigment epithelial cells, the outer plexiform layer, and photoreceptor inner
      segments. Most intensive VEGF expression was documented after HF diet.
      CONCLUSION: LDL receptor deficient mice exhibit an accumulation of lipid
      particles in BrM which is further increased after fat intake. VEGF expression is
      found in the outer retinal layers of LDL receptor deficient mice and appears to
      correlate with the amount of lipid particles present in BrM.

PMID- 16299145
TI  - Advanced glycation end products can induce glial reaction and neuronal
      degeneration in retinal explants.
AB  - BACKGROUND/AIMS: Neuronal degeneration has been reported to occur in diabetic
      retinopathy before the onset of detectable microvascular abnormalities. To
      investigate whether advanced glycation end products (AGE) could be directly
      responsible for retinal neurodegeneration, retinal explants were incubated with
      glycated bovine serum albumin (BSA). METHODS: Retinal explants obtained from non
      diabetic adult rats were incubated 4 days with or without 200 mug/ml glycated
      BSA. Neural apoptosis was quantified by terminal dUTP nick end labelling (TUNEL)
      binding and immunostaining with anti-cleaved caspase-3 antibody. Expression of
      glial fibrillary acidic protein (GFAP) was localised by immunofluorescence.
      RESULTS: TUNEL and cleaved caspase-3 positive cells increased significantly by
      2.2-fold and 2.5-fold in retinal explants incubated in glycated BSA (p<0.05),
      respectively. The ganglion cell layer was the most sensitive retinal layer to the
      glycated BSA. Neuronal degeneration was confirmed by the increased GFAP labelling
      in Muller glial cells from retinal explants treated with glycated BSA.
      CONCLUSION: These results suggest that AGE could induce retinal neurodegeneration
      in the absence of blood perfusion. Cells in the ganglion cell layer appeared to
      be the most sensitive as in diabetic retinopathy and its animal models. AGE
      toxicity could therefore contribute to the early pathological mechanisms of
      diabetic retinopathy.

PMID- 16299143
TI  - Unilateral electronegative ERG of non-vascular aetiology.
AB  - BACKGROUND: Full field and pattern electroretinograms (ERG, PERG) are performed
      to assess generalised retinal function and macular function, respectively. An
      (electro) negative full field ERG usually describes an ISCEV standard maximal
      response in which the b-wave is smaller than a normal or minimally reduced a-wave
      and indicates dysfunction that is post-phototransduction. The most common cause
      of a unilateral negative ERG is central retinal artery occlusion (CRAO) or
      birdshot chorioretinopathy (BCR). This study examines the clinical and
      electrophysiological features of patients with unilateral negative ERG who do not
      have CRAO or BCR. METHODS: 12 patients were ascertained with a unilateral
      negative ERG in whom a vascular aetiology and BCR were excluded. Most presented
      with symptoms of central retinal dysfunction. In 11 of the 12 patients additional
      long duration photopic stimuli were used to test cone system ON and OFF
      responses. RESULTS: All 12 patients had unilateral electronegative bright flash
      full field ERGs indicating total or relative preservation of rod photoreceptor
      function, but dysfunction post-phototransduction. Seven of these patients had non
      specific inflammatory changes in the eye with the negative ERG. Six patients,
      including five with inflammatory signs, had involvement of the cone ON response
      with complete preservation of cone OFF responses. A further three patients showed
      evidence of cone ON response abnormality with less severe OFF response
      involvement. CONCLUSION: The ERGs in this heterogeneous group of patients
      predominantly showed post-phototransduction involvement of the ON pathways.
      Sparing of the cone OFF response was often observed. The majority of patients had
      signs of previous inflammation and it is speculated that these highly unusual
      unilateral changes may be mediated via an autoimmune mechanism.

PMID- 16299146
TI  - 5,10-Methylenetetrahydrofolate reductase C677T gene polymorphism in Behcet's
      patients with or without ocular involvement.
AB  - BACKGROUND: Increased serum levels of homocysteine (Hcy) have been reported in
      patients with Behcet's disease (BD) with an established risk factor for vascular
      involvement. Recently, the authors demonstrated that elevated Hcy levels are
      associated with ocular involvement in such patients. On the other hand, elevated
      levels of Hcy can result from genetic errors. Indeed, a mutation in the 5,10
      methylenetetrahydrofolate reductase (MTHFR C677T) gene influences Hcy metabolism
      and, therefore, MTHFR C677T polymorphism provokes hyperhomocysteinaemia. AIM: To
      investigate the possible genetic factor for the elevation of plasma Hcy level in
      patients with BD by examining gene interaction with the MTHFR C677T polymorphism,
      a crucial factor of the Hcy metabolism. In addition, the authors aimed to
      evaluate if there is an association between the C677T polymorphism and the
      presence of ocular involvement in such patients. METHOD: A total of 59 patients
      with BD (25 men, 34 women) with a mean age of 34.9 years and 42 age and sex
      matched healthy control subjects (19 men, 23 women; mean age 32.2) were included
      in this investigation. MTHFR gene polymorphism was investigated by the polymerase
      chain reaction (PCR) and restriction fragment length polymorphism (RFLP) of a
      genomic DNA fragment at nucleotide 677 in all subjects in both groups. The
      genetic equilibrium is assumed for the gene frequencies of the MTHFR polymorphism
      in both samples. RESULTS: The genotype of the MTHFR gene differed between the
      Behcet's patients and control subjects (TT: 11.9 v 2.4%; CT: 55.9 v 61.9%; CC:
      32.2 v 35.7 %). TT homozygous genotype was more frequently in BD patients than
      the controls, though the difference was not significant (p = 0.063). In BD
      patients with ocular involvement, however, the frequencies of MTHFR TT
      homogenetic type (27.8%) were significantly and statistically higher than those
      in BD patients without ocular involvement (4.9%, p = 0.022, odds ratio = 7.5), or
      the controls (2.4%, p = 0.003, odds ratio = 20.0). TT homozygous genotype was
      associated with an increased risk for ocular involvement. CONCLUSION: Elevated
      serum levels of Hcy seem to be a result of C677T polymorphism of the MTHFR gene,
      with increased TT individuals over CC and CT genotype BD patients. Although no
      association was shown between the MTHFR reductase C677T polymorphism and the
      increased risk of oral aphtahe or genital ulcers, a mutation in this gene was
      associated with an increased risk of ocular involvement, suggesting genetic
      instability with a potential initiation of Hcy lowering therapy in this patient
      group.

PMID- 16299148
TI  - Expression of FGFR-2 and FGFR-3 in the normal human fetal orbit.
AB  - AIMS: To demonstrate the expression patterns of two fibroblast growth factor
      receptors (FGFR-2 and FGFR-3) in the normal human fetal orbit. METHODS: 6 microm
      orbital slide sections were prepared from 12 week old human fetal material
      obtained within established ethical guidelines. Radioactive in situ hybridisation
      techniques were used to demonstrate the expression patterns of FGFR-2 and FGFR-3
      within these sections. Only one foetus had appropriate orbital sections taken.
      RESULTS: FGFR-2 was expressed within the extraocular muscles (EOMs) and the optic
      nerve sheath and to a lesser degree within the orbital periosteal margins and the
      cranial sutures. FGFR-3 was expressed a lot within the periosteal margins and
      cranial sutures but not within either the EOMs or the optic nerve sheath.
      CONCLUSIONS: FGFR-2 and FGFR-3 are differentially expressed within different
      orbital components. FGFR-2 gene mutations may be responsible for craniosynostotic
      syndromes such as Crouzon, Pfeiffer, and Apert, while those in the FGFR-3 gene
      may cause isolated unicoronal synostosis. EOMs may be histologically abnormal in
      cases of Apert, Pfeiffer, and Crouzon syndromes but not isolated unicoronal
      synostosis. The pattern of expression of FGFR-2 in the normal human fetal orbit
      may explain some of the EOM histological findings seen in some cases of Apert,
      Pfeiffer, and Crouzon syndromes.

PMID- 16299147
TI  - Gremlin gene expression in bovine retinal pericytes exposed to elevated glucose.
AB  - AIM: To assess the influence of high extracellular glucose on the expression of
      the bone morphogenetic protein (BMP) antagonist, gremlin, in cultured bovine
      retinal pericytes (BRPC). METHODS: BRPC were cultured under conditions of 5 mM
      and 30 mM d-glucose for 7 days and total RNA was isolated. Gremlin mRNA levels
      were correlated, by RT-PCR, with other genes implicated in the pathogenesis of
      diabetic retinopathy and the signalling pathways in high glucose induced gremlin
      expression were probed using physiological inhibitors. Gremlin expression was
      also examined in the retina of streptozotocin induced diabetic mice. RESULTS:
      High glucose stimulated a striking increase in BRPC gremlin mRNA levels in
      parallel with increases in mRNA for the growth factors vascular endothelial
      growth factor (VEGF), transforming growth factor beta (TGFbeta), and connective
      tissue growth factor (CTGF) and changes in other genes including fibronectin and
      plasminogen activator inhibitor-1 (PAI-1). High glucose triggered gremlin
      expression was modulated by anti-TGFbeta antibody, by the uncoupler of oxidative
      phosphorylation, CCCP, and by inhibition of MAP-kinase (MAPK) activation.
      Striking gremlin expression was observed in the outer retina of diabetic mice and
      also at the level of the vascular wall. CONCLUSIONS: Gremlin gene expression is
      induced in BRPC in response to elevated glucose and in the retina of the
      streptozotocin induced diabetic mouse. Its expression is modulated by
      hyperglycaemic induction of the MAPK, reactive oxygen species, and TGFbeta
      pathways, all of which are reported to have a role in diabetic fibrotic disease.
      This implicates a role for gremlin in the pathogenesis of diabetic retinopathy.

PMID- 16299150
TI  - Impression cytology of the ocular surface.
AB  - Impression cytology refers to the application of a cellulose acetate filter to
      the ocular surface to remove the superficial layers of the ocular surface
      epithelium. These cells can then be subjected to histological,
      immunohistological, or molecular analysis. Proper technique is essential as the
      number of cells sampled can vary considerably. Generally two to three layers of
      cells are removed in one application but deeper cells can be accessed by repeat
      application over the same site. Applications for impression cytology include
      diagnosing a wide range of ocular surface disorders, documenting sequential
      changes in the conjunctival and corneal surface over time, staging conjunctival
      squamous metaplasia, and monitoring effects of treatment. It is also a useful
      investigational tool for analysing ocular surface disease with immunostaining and
      DNA analysis. It is non-invasive, relatively easy to perform, and yields reliable
      information about the area sampled with minimal discomfort to the patient. Major
      ophthalmic centres should develop and introduce this technique into routine
      clinical practice. This is best achieved with a team approach including the
      ophthalmologist, pathologist, microbiologist, and the immunologist.

PMID- 16299151
TI  - Ultrahigh resolution optical coherence tomography of birdshot
      retinochoroidopathy.

PMID- 16299152
TI  - Unilateral necrotising toxoplasmic retinochoroiditis as the main clinical
      manifestation of a peptide transporter (TAP) deficiency.

PMID- 16299149
TI  - Hypertensive retinopathy revisited: some answers, more questions.
AB  - Hypertension is associated with cardiovascular risk and systemic target organ
      damage. Retinopathy is considered one of the indicators of target organ damage.
      This review focuses on recent studies on hypertensive retinopathy and their
      implications for clinical care. Early recognition of hypertensive retinopathy
      signs remains an important step in the risk stratification of hypertensive
      patients.

PMID- 16299153
TI  - Scleral contact lenses are not optically inferior to corneal lenses.

PMID- 16299154
TI  - Retinal changes in juvenile X linked retinoschisis using three dimensional
      optical coherence tomography.

PMID- 16299155
TI  - Optometric referrals: towards a two way flow of information?

PMID- 16299156
TI  - Linezolid induced toxic optic neuropathy.

PMID- 16299157
TI  - Delayed progressive visual loss following wrapping of bilateral clinoidal
      aneurysms: recovery of vision and improvement in neuroimaging during
      corticosteroid treatment.

PMID- 16299158
TI  - Visual loss after silicone oil removal.

PMID- 16299159
TI  - Visual loss may be due to silicone oil tamponade effect rather than silicone oil
      removal.

PMID- 16299160
TI  - Visual loss following silicone oil removal.

PMID- 16299163
TI  - Demonstration of docosahexaenoic acid as a bioavailability enhancer for CYP3A
      substrates: in vitro and in vivo evidence using cyclosporin in rats.
AB  - To investigate the pharmacokinetic interaction between cyclosporin A (CsA) and
      docosahexaenoic acid (DHA) in vivo, 5 mg/kg CsA was orally or intravenously
      coadministered with DHA (50-200 microg/kg) to rats. The effect of DHA on CYP3A
      activity was determined using rat liver microsomes in vitro. Moreover, the effect
      of DHA on P-glycoprotein (P-gp) function was examined using cultured Caco-2 cells
      in vitro. After oral coadministration of CsA with 100 microg/kg and 200 microg/kg
      DHA, bioavailability (BA) was significantly increased, compared with control
      rats. In contrast, no pharmacokinetic interaction was observed when CsA was
      intravenously administered in rats dosed orally with DHA, suggesting that DHA did
      not affect hepatic metabolism. The formation of 6beta-hydroxytestosterone from
      testosterone in rat liver microsomes was competitively inhibited by DHA. The Km,
      Vmax, and Ki values were 25.5 microM, 2.45 nmol/min/mg protein, and 5.52 microM,
      respectively. Moreover, basal-to-apical transport of [3H]CsA in the Caco-2 cell
      monolayer was not affected by DHA but was decreased by valspodar (PSC 833), a P
      gp inhibitor. Our finding is the first to indicate that DHA inhibits intestinal
      CYP3A both in vitro and in vivo, but not P-gp. It was thus demonstrated that DHA
      could be used as a BA enhancer for the drugs that are extensively metabolized by
      CYP3A in the gut.

PMID- 16299162
TI  - Development of novel furanocoumarin dimers as potent and selective inhibitors of
      CYP3A4.
AB  - Grapefruit juice has been found to cause an increase in the oral bioavailability
      of many therapeutic agents. Such interactions are believed to result from the
      mechanism-based inhibition of CYP3A4 activity in the intestine. Furanocoumarin
      dimers present in the juice have been found to be extremely potent inhibitors of
      CYP3A4 activity. The aim of this work was to synthesize and test a series of
      dimers with a view to defining the relationship between structure and inhibitory
      activity and establish whether they might make suitable probes of CYP3A4
      activity. Eleven furanocoumarin dimers were synthesized and evaluated as
      inhibitors of CYP3A4 using human liver microsomes, with testosterone as the
      marker substrate. Four of the most potent dimers were also investigated for their
      effects on CYP3A4 activity in the human intestine and on five additional hepatic
      cytochrome P450 isoforms. The dimers showed potent dose-dependent inhibition of
      CYP3A4 activity in both liver and intestine; IC50 values ranged from 0.021 +/-
      0.002 to 0.146 +/- 0.041 microM (mean +/- S.D. n = 3). Of the four dimers
      evaluated further, all showed time-dependent inhibition of CYP3A4 activity.
      88Prop showed moderate inhibition of both CYP2C19 and CYP1A2 with IC50 values of
      4.42 +/- 0.01 and 1.98 +/- 0.34 microM, 88Octa was found to inhibit CYP2C19 (IC50
      = 3.16 +/- 0.01 microM) and 58Prop to inhibit CYP1A2 (IC50 = 2.39 +/- 0.77
      microM). Minimal inhibition of CYP2D6 and CYP2C9 was observed (IC50 > 10 microM).
      In conclusion, all the dimers tested were extremely potent inhibitors of CYP3A4
      activity. In particular, dimer 55EE was highly selective toward the enzyme,
      suggesting that this compound is a suitable probe for determining the
      contribution of CYP3A4 to drug metabolism.

PMID- 16299161
TI  - Glucuronidation converts gemfibrozil to a potent, metabolism-dependent inhibitor
      of CYP2C8: implications for drug-drug interactions.
AB  - Gemfibrozil more potently inhibits CYP2C9 than CYP2C8 in vitro, and yet the
      opposite inhibitory potency is observed in the clinic. To investigate this
      apparent paradox, we evaluated both gemfibrozil and its major metabolite, an acyl
      glucuronide (gemfibrozil 1-O-beta-glucuronide) as direct-acting and metabolism
      dependent inhibitors of the major drug-metabolizing cytochrome P450 enzymes
      (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4) in human liver microsomes.
      Gemfibrozil most potently inhibited CYP2C9 (IC50 of 30 microM), whereas
      gemfibrozil glucuronide most potently inhibited CYP2C8 (IC50 of 24 microM).
      Unexpectedly, gemfibrozil glucuronide, but not gemfibrozil, was found to be a
      metabolism-dependent inhibitor of CYP2C8 only. The IC50 for inhibition of CYP2C8
      by gemfibrozil glucuronide decreased from 24 microM to 1.8 microM after a 30-min
      incubation with human liver microsomes and NADPH. Inactivation of CYP2C8 by
      gemfibrozil glucuronide required NADPH, and proceeded with a K(I) (inhibitor
      concentration that supports half the maximal rate of enzyme inactivation) of 20
      to 52 microM and a k(inact) (maximal rate of inactivation) of 0.21 min(-1).
      Potent inhibition of CYP2C8 was also achieved by first incubating gemfibrozil
      with alamethicin-activated human liver microsomes and UDP-glucuronic acid (to
      form gemfibrozil glucuronide), followed by a second incubation with NADPH. Liquid
      chromatography-tandem mass spectrometry analysis established that human liver
      microsomes and recombinant CYP2C8 both convert gemfibrozil glucuronide to a
      hydroxylated metabolite, with oxidative metabolism occurring on the
      dimethylphenoxy moiety (the group furthest from the glucuronide moiety). The
      results described have important implications for the mechanism of the clinical
      interaction reported between gemfibrozil and CYP2C8 substrates such as
      cerivastatin, repaglinide, rosiglitazone, and pioglitazone.

PMID- 16299164
TI  - Inefficient repair of tamoxifen-DNA adducts in rats and mice.
AB  - A long-term treatment with tamoxifen (TAM) to women increases the risk of
      developing endometrial cancer. The cancer may result from genotoxic damage
      induced by this drug. In fact, TAM-DNA adducts were detected in the liver of rats
      treated with TAM and initiated to develop hepatocellular carcinomas. To explore
      the distribution and repair rate of TAM-DNA adducts, the level of TAM-DNA adducts
      in all tissues of rats and mice was monitored for 28 days and 7 days,
      respectively, after the termination of TAM treatment, using 32P
      postlabeling/polyacrylamide gel electrophoresis and 32P-postlabeling/HPLC
      analyses. TAM-DNA adducts were formed specifically in the liver of rodents. In
      rats, the level of hepatic TAM-DNA adducts was decreased only to 43% in 28 days,
      indicating that the half-life of adducts was approximately 25 days. Among trans
      [fraction (fr)-1 and fr-2]- and cis (fr-3 and fr-4)-isoforms of TAM-DNA adducts,
      a trans-form (fr-1) was removed much more slowly than other adducts, indicating
      that the repair rate of TAM-DNA adducts varied depending on the structure of
      isoforms. The repair rate of TAM-DNA adducts was also compared between nucleotide
      excision repair-deficient (Xpc knockout) and wild mice. Although the level of
      hepatic TAM-DNA adducts observed with Xpc knockout mice was slightly higher than
      that of the wild type, the removal of TAM-DNA adducts in both mice was only 20%
      in 7 days. Thus, TAM-DNA adducts are not efficiently repaired from the targeted
      tissue, leading to the development of cancer.

PMID- 16299165
TI  - Estimation of aldehyde oxidase activity in vivo from conversion ratio of N1
      methylnicotinamide to pyridones, and intraspecies variation of the enzyme
      activity in rats.
AB  - The in vivo conversion ratio of N1-methylnicotinamide (NMN) to N1-methyl-2
      pyridone-5-carboxamide (2-PY) and N1-methyl-4-pyridone-3-carboxamide (4-PY) as a
      parameter for the estimation of aldehyde oxidase level in rats was examined. NMN
      and its pyridones (2-PY and 4-PY) are usually detected in the urine of rats. When
      we measured the ratio of the amount of pyridones to the total amount of NMN and
      pyridones (RP value) in the urine of rats, marked intraspecies variations were
      observed. The variation in RP value among strains was closely related to the
      differences of liver aldehyde oxidase activity measured with NMN as a substrate.
      RP values after administration of NMN to different strains of rats confirmed the
      existence of strain differences of aldehyde oxidase activity in vivo. We
      demonstrated that measurements of NMN and its pyridones usually excreted in the
      urine can be used to predict the in vivo level of aldehyde oxidase.

PMID- 16299166
TI  - Distribution of (7alpha)-21-[4-[(diethylamino) methyl]-2-methoxyphenoxy]-7-methyl
      19-norpregna-1,3,5(10)-trien-3-ol-20-[14C]2-hydroxy-1,2,3-propanetricarboxylate
      ([14C]TAS-108) and its metabolites after single oral administration to rats
      bearing 7,12-dimethylbenz(alpha)anthracene-induced mammary tumor.
AB  - (7Alpha)-21-[4-[(diethylamino)methyl]-2-methoxyphenoxy]-7-methyl-19-norpregna
      1,3,5(10)-trien-3-ol 2-hydroxy-1,2,3-propanetricarboxylate (TAS-108) is a novel
      steroidal antiestrogen, modulating the differential recruitment of
      transcriptional cofactors by liganded estrogen receptors and representing a
      promising agent for the treatment of breast cancer. To understand better the
      relationships between the drug exposure and the efficacy or toxicity of TAS-108,
      we investigated the metabolism and distribution of TAS-108 after oral
      administration of [14C]TAS-108 to rats bearing a 7,12
      dimethylbenz(alpha)anthracene-induced mammary carcinoma. The metabolites (7alpha)
      21-[4-[(ethylamino)methyl]-2-methoxyphenoxy]-7-methyl-19-norpregna-1,3,5(10)
      trien-3-ol (deEt-TAS-108), (7alpha)-21-[4-[(diethylamino)methyl]-2
      methoxyphenoxy]-7-methyl-19-norpregna-1,3,5(10)-trien-3-ol-N-oxide (TAS-108-N
      oxide), and 3-methoxy-4-[(7alpha)-7-methyl-19-norpregna-1,3,5(10)-trien-3-ol-21
      yl]oxybenzoic acid (TAS-108-COOH) were identified as the major metabolites in the
      plasma, and in addition, (7alpha)-21-[4-[(ethylamino)methyl]-2-methoxyphenoxy]-3
      methoxy-7-methyl-19-norpregna-1,3,5(10)-triene (O-Me-deEt-TAS-108) was identified
      as a novel metabolite in this study. The time-concentration profiles of TAS-108
      and its metabolites in the plasma were compared with those in the tumor and
      uterus of the rats. Radioactivity was found at a high level in various organs
      including lung, liver, spleen, ovary, and many glands at 12 h and was relatively
      higher in tumor tissue than in plasma. On the other hand, the levels of
      radioactivity in the brain and eyeball were very low or not detectable. TAS-108,
      deEt-TAS-108, and O-Me-deEt-TAS-108 were extensively distributed in the rat
      tissues and the tumor, with corresponding tissue/plasma ratios for Cmax and area
      under the curve in the range of 7 to 100. In contrast, TAS-108-COOH and TAS-108-N
      oxide were hardly distributed to the tissues and thus may not contribute to the
      efficacy or toxicity of TAS-108. Thus, TAS-108, deEt-TAS-108, and O-Me-deEt-TAS
      108, being distributed highly in tumor tissue, may be more important for the
      efficacy and toxicity of TAS-108 in vivo than TAS-108-COOH and TAS-108-N-oxide.

PMID- 16299167
TI  - The rice dwarf virus P2 protein interacts with ent-kaurene oxidases in vivo,
      leading to reduced biosynthesis of gibberellins and rice dwarf symptoms.
AB  - The mechanisms of viral diseases are a major focus of biology. Despite intensive
      investigations, how a plant virus interacts with host factors to cause diseases
      remains poorly understood. The Rice dwarf virus (RDV), a member of the genus
      Phytoreovirus, causes dwarfed growth phenotypes in infected rice (Oryza sativa)
      plants. The outer capsid protein P2 is essential during RDV infection of insects
      and thus influences transmission of RDV by the insect vector. However, its role
      during RDV infection within the rice host is unknown. By yeast two-hybrid and
      coimmunoprecipitation assays, we report that P2 of RDV interacts with ent-kaurene
      oxidases, which play a key role in the biosynthesis of plant growth hormones
      gibberellins, in infected plants. Furthermore, the expression of ent-kaurene
      oxidases was reduced in the infected plants. The level of endogenous GA1 (a major
      active gibberellin in rice vegetative tissues) in the RDV-infected plants was
      lower than that in healthy plants. Exogenous application of GA3 to RDV-infected
      rice plants restored the normal growth phenotypes. These results provide evidence
      that the P2 protein of RDV interferes with the function of a cellular factor,
      through direct physical interactions, that is important for the biosynthesis of a
      growth hormone leading to symptom expression. In addition, the interaction
      between P2 and rice ent-kaurene oxidase-like proteins may decrease phytoalexin
      biosynthesis and make plants more competent for virus replication. Moreover, P2
      may provide a novel tool to investigate the regulation of GA metabolism for plant
      growth and development.

PMID- 16299168
TI  - Inhibition of target of rapamycin signaling by rapamycin in the unicellular green
      alga Chlamydomonas reinhardtii.
AB  - The macrolide rapamycin specifically binds the 12-kD FK506-binding protein
      (FKBP12), and this complex potently inhibits the target of rapamycin (TOR)
      kinase. The identification of TOR in Arabidopsis (Arabidopsis thaliana) revealed
      that TOR is conserved in photosynthetic eukaryotes. However, research on TOR
      signaling in plants has been hampered by the natural resistance of plants to
      rapamycin. Here, we report TOR inactivation by rapamycin treatment in a
      photosynthetic organism. We identified and characterized TOR and FKBP12 homologs
      in the unicellular green alga Chlamydomonas reinhardtii. Whereas growth of wild
      type Chlamydomonas cells is sensitive to rapamycin, cells lacking FKBP12 are
      fully resistant to the drug, indicating that this protein mediates rapamycin
      action to inhibit cell growth. Unlike its plant homolog, Chlamydomonas FKBP12
      exhibits high affinity to rapamycin in vivo, which was increased by mutation of
      conserved residues in the drug-binding pocket. Furthermore, pull-down assays
      demonstrated that TOR binds FKBP12 in the presence of rapamycin. Finally,
      rapamycin treatment resulted in a pronounced increase of vacuole size that
      resembled autophagic-like processes. Thus, our findings suggest that
      Chlamydomonas cell growth is positively controlled by a conserved TOR kinase and
      establish this unicellular alga as a useful model system for studying TOR
      signaling in photosynthetic eukaryotes.

PMID- 16299169
TI  - Cuticular lipid composition, surface structure, and gene expression in
      Arabidopsis stem epidermis.
AB  - All vascular plants are protected from the environment by a cuticle, a lipophilic
      layer synthesized by epidermal cells and composed of a cutin polymer matrix and
      waxes. The mechanism by which epidermal cells accumulate and assemble cuticle
      components in rapidly expanding organs is largely unknown. We have begun to
      address this question by analyzing the lipid compositional variance, the surface
      micromorphology, and the transcriptome of epidermal cells in elongating
      Arabidopsis (Arabidopsis thaliana) stems. The rate of cell elongation is maximal
      near the apical meristem and decreases steeply toward the middle of the stem,
      where it is 10 times slower. During and after this elongation, the cuticular wax
      load and composition remain remarkably constant (32 microg/cm2), indicating that
      the biosynthetic flux into waxes is closely matched to surface area expansion. By
      contrast, the load of polyester monomers per unit surface area decreases more
      than 2-fold from the upper (8 microg/cm2) to the lower (3 microg/cm2) portion of
      the stem, although the compositional variance is minor. To aid identification of
      proteins involved in the biosynthesis of waxes and cutin, we have isolated
      epidermal peels from Arabidopsis stems and determined transcript profiles in both
      rapidly expanding and nonexpanding cells. This transcriptome analysis was
      validated by the correct classification of known epidermis-specific genes. The
      15% transcripts preferentially expressed in the epidermis were enriched in genes
      encoding proteins predicted to be membrane associated and involved in lipid
      metabolism. An analysis of the lipid-related subset is presented.

PMID- 16299170
TI  - The alternative oxidase of plant mitochondria is involved in the acclimation of
      shoot growth at low temperature. A study of Arabidopsis AOX1a transgenic plants.
AB  - The alternative oxidase (AOX) pathway of plant mitochondria uncouples respiration
      from mitochondrial ATP production and may ameliorate plant performance under
      stressful environmental conditions, such as cold temperatures, by preventing
      excess accumulation of reactive oxygen species. We tested this model in whole
      tissues by growing AtAOX1a-transformed Arabidopsis (Arabidopsis thaliana) plants
      at 12 degrees C. For the first time, to our knowledge, in plants genetically
      engineered for AOX, we identified a vegetative shoot growth phenotype. Compared
      with wild type at day 21 after sowing, anti-sense and overexpressing lines
      showed, on average, 27% reduced leaf area and 25% smaller rosettes versus 30%
      increased leaf area and 33% larger rosette size, respectively. Lines
      overexpressing a mutated, constitutively active AOX1a showed smaller phenotypic
      effects. These phenotypic differences were not the result of a major alteration
      of the tissue redox state because the changes in levels of lipid peroxidation
      products, reflecting oxidative damage, and the expression of genes encoding
      antioxidant and electron transfer chain redox enzymes did not correspond with the
      shoot phenotypes. However, the observed phenotypes were correlated with the
      amount of total shoot anthocyanin at low temperature and with the transcription
      of the flavonoid pathway genes PAL1 and CHS. These results demonstrate that (1)
      AOX activity plays a role in shoot acclimation to low temperature in Arabidopsis,
      and that (2) AOX not only functions to prevent excess reactive oxygen species
      formation in whole tissues under stressful environmental conditions but also
      affects metabolism through more pervasive effects, including some that are
      extramitochondrial.

PMID- 16299171
TI  - Characterization of transformed Arabidopsis with altered alternative oxidase
      levels and analysis of effects on reactive oxygen species in tissue.
AB  - The alternative oxidase (AOX) of plant mitochondria transfers electrons from the
      ubiquinone pool to oxygen without energy conservation. AOX can use reductant in
      excess of cytochrome pathway capacity, preventing reactive oxygen species (ROS)
      formation from an over-reduced ubiquinone pool, and thus may be involved in
      acclimation to oxidative stresses. The AOX connection with mitochondrial ROS has
      been investigated only in isolated mitochondria and suspension culture cells. To
      study ROS and AOX in whole plants, transformed lines of Arabidopsis (Arabidopsis
      thaliana) were generated: AtAOX1a overexpressors, AtAOX1a anti-sense plants, and
      overexpressors of a mutated, constitutively active AtAOX1a. In the presence of
      KCN, leaf tissue of either mutant or wild-type AOX overexpressors showed no
      increase in oxidative damage, whereas anti-sense lines had levels of damage
      greater than those observed for untransformed leaves. Similarly, ROS production
      increased markedly in anti-sense and untransformed, but not overexpressor, roots
      with KCN treatment. Thus, AOX functions in leaves and roots, as in suspension
      cells, to ameliorate ROS production when the cytochrome pathway is chemically
      inhibited. However, in contrast with suspension culture cells, no changes in leaf
      transcript levels of selected electron transport components or oxidative stress
      related enzymes were detected under nonlimiting growth conditions, regardless of
      transformation type. Further, a microarray study using an anti-sense line showed
      AOX influences outside mitochondria, particularly in chloroplasts and on several
      carbon metabolism pathways. These results illustrate the value of expanding AOX
      transformant studies to whole tissues.

PMID- 16299172
TI  - Premature leaf senescence modulated by the Arabidopsis PHYTOALEXIN DEFICIENT4
      gene is associated with defense against the phloem-feeding green peach aphid.
AB  - Aphids, which are phloem-feeding insects, cause extensive loss of plant
      productivity and are vectors of plant viruses. Aphid feeding causes changes in
      resource allocation in the host, resulting in an increase in flow of nutrients to
      the insect-infested tissue. We hypothesized that leaf senescence, which is
      involved in the programmed degradation of cellular components and the export of
      nutrients out of the senescing leaf, could be utilized by plants to limit aphid
      growth. Using Arabidopsis (Arabidopsis thaliana) and green peach aphid (GPA;
      Myzus persicae Sulzer), we found that GPA feeding induced premature chlorosis and
      cell death, and increased the expression of SENESCENCE ASSOCIATED GENES (SAGs),
      all hallmarks of leaf senescence. Hypersenescence was accompanied by enhanced
      resistance against GPA in the Arabidopsis constitutive expresser of PR genes5 and
      suppressor of SA insensitivity2 mutant plants. In contrast, resistance against
      GPA was compromised in the phytoalexin deficient4 (pad4) mutant plant. The PAD4
      gene, which is expressed at elevated level in response to GPA feeding, modulates
      the GPA feeding-induced leaf senescence. In comparison to the wild-type plant,
      GPA feeding-induced chlorophyll loss, cell death, and SAG expression were delayed
      in the pad4 mutant. Although PAD4 is associated with camalexin synthesis and
      salicylic acid (SA) signaling, camalexin and SA signaling are not important for
      restricting GPA growth; growth of GPA on the camalexin-biosynthesis mutant, pad3,
      and the SA deficient2 and NahG plants and the SA-signaling mutant, nonexpresser
      of PR genes1, were comparable to that on the wild-type plant. Our results suggest
      that PAD4 modulates the activation of senescence in the aphid-infested leaves,
      which contributes to basal resistance to GPA.

PMID- 16299173
TI  - Protection against photooxidative injury of tobacco leaves by 2-alkenal
      reductase. Detoxication of lipid peroxide-derived reactive carbonyls.
AB  - Degradation of lipid peroxides leads to the formation of cytotoxic 2-alkenals and
      oxenes (collectively designated reactive carbonyls). The novel NADPH-dependent
      oxidoreductase 2-alkenal reductase (AER; EC 1.3.1.74) from Arabidopsis
      (Arabidopsis thaliana), which is encoded by the gene At5g16970, catalyzes the
      reduction of the alpha,beta-unsaturated bond of reactive carbonyls, and hence is
      presumed to function in antioxidative defense in plants. Here we show that
      Arabidopsis AER (At-AER) has a broad substrate spectrum to biologically relevant
      reactive carbonyls. Besides 2-alkenals, the enzyme recognized as substrates the
      lipid peroxide-derived oxenes 9-oxo-octadeca-(10E),(12Z)-dienoic acid and 13-oxo
      octadeca-(9E),(11Z)-dienoic acid, as well as the potent genotoxin 4-oxo-(2E)
      nonenal, altogether suggesting AER has a key role in the detoxification of
      reactive carbonyls. To validate this conclusion by in vivo studies, transgenic
      tobacco (Nicotiana tabacum) plants that had 100- to 250-fold higher AER activity
      levels than control plants were generated. The engineered plants exhibited
      significantly less damage from either (1) the exogenously administered 4-hydroxy
      (2E)-nonenal, (2) treatment with methyl viologen plus light, or (3) intense
      light. We further show that the At-AER protein fused with the Aequorea victoria
      green fluorescent protein localizes in cytosol and the nucleus in Bright-Yellow 2
      cells. These results indicate that reactive carbonyls mediate photooxidative
      injury in leaf cells, and At-AER in the cytosol protects the cells by reducing
      the alpha,beta-unsaturated bond of the photoproduced reactive carbonyls.

PMID- 16299174
TI  - Biotin synthesis in plants. The first committed step of the pathway is catalyzed
      by a cytosolic 7-keto-8-aminopelargonic acid synthase.
AB  - Biochemical and molecular characterization of the biotin biosynthetic pathway in
      plants has dealt primarily with biotin synthase. This enzyme catalyzing the last
      step of the pathway is localized in mitochondria. Other enzymes of the pathway
      are however largely unknown. In this study, a genomic-based approach allowed us
      to clone an Arabidopsis (Arabidopsis thaliana) cDNA coding 7-keto-8
      aminopelargonic acid (KAPA) synthase, the first committed enzyme of the biotin
      synthesis pathway, which we named AtbioF. The function of the enzyme was
      demonstrated by functional complementation of an Escherichia coli mutant
      deficient in KAPA synthase reaction, and by measuring in vitro activity.
      Overproduction and purification of recombinant AtbioF protein enabled a thorough
      characterization of the kinetic properties of the enzyme and a spectroscopic
      study of the enzyme interaction with its substrates and product. This is the
      first characterization of a KAPA synthase reaction in eukaryotes. Finally, both
      green fluorescent protein-targeting experiments and western-blot analyses showed
      that the Arabidopsis KAPA synthase is present in cytosol, thus revealing a unique
      compartmentation of the plant biotin synthesis, split between cytosol and
      mitochondria. The significance of the complex compartmentation of biotin
      synthesis and utilization in the plant cell and its potential importance in the
      regulation of biotin metabolism are also discussed.

PMID- 16299175
TI  - Populus euphratica displays apoplastic sodium accumulation, osmotic adjustment by
      decreases in calcium and soluble carbohydrates, and develops leaf succulence
      under salt stress.
AB  - Populus euphratica Olivier is known to exist in saline and arid environments. In
      this study we investigated the physiological mechanisms enabling this species to
      cope with stress caused by salinity. Acclimation to increasing Na+ concentrations
      required adjustments of the osmotic pressure of leaves, which were achieved by
      accumulation of Na+ and compensatory decreases in calcium and soluble
      carbohydrates. The counterbalance of Na+/Ca2+ was also observed in mature leaves
      from field-grown P. euphratica trees exposed to an environmental gradient of
      increasing salinity. X-ray microanalysis showed that a primary strategy to
      protect the cytosol against sodium toxicity was apoplastic but not vacuolar salt
      accumulation. The ability to cope with salinity also included maintenance of
      cytosolic potassium concentrations and development of leaf succulence due to an
      increase in cell number and cell volume leading to sodium dilution. Decreases in
      apoplastic and vacuolar Ca2+ combined with suppression of calcineurin B-like
      protein transcripts suggest that Na+ adaptation required suppression of calcium
      related signaling pathways. Significant increases in galactinol synthase and
      alternative oxidase after salt shock and salt adaptation point to shifts in
      carbohydrate metabolism and suppression of reactive oxygen species in
      mitochondria under salt stress.

PMID- 16299176
TI  - Effects of brefeldin A on pollen germination and tube growth. Antagonistic
      effects on endocytosis and secretion.
AB  - We assessed the effects of brefeldin A (BFA) on pollen tube development in Picea
      meyeri using fluorescent marker FM4-64 as a membrane-inserted endocytic/recycling
      marker, together with ultrastructural studies and Fourier transform infrared
      analysis of cell walls. BFA inhibited pollen germination and pollen tube growth,
      causing morphological changes in a dose-dependent manner, and pollen tube tip
      growth recovered after transferring into BFA-free medium. FM4-64 labeling showed
      typical bright apical staining in normally growing P. meyeri pollen tubes; this
      apical staining pattern differed from the V-formation pattern found in angiosperm
      pollen tubes. Confocal microscopy revealed that exocytosis was greatly inhibited
      in the presence of BFA. In contrast, the overall uptake of FM4-64 dye was about 2
      fold that in the control after BFA (5 microg mL(-1)) treatment, revealing that
      BFA stimulated endocytosis in a manner opposite to the induced changes in
      exocytosis. Transmission electron microscopic observation showed that the number
      of secretory vesicles at the apical zone dramatically decreased, together with
      the disappearance of paramural bodies, while the number of vacuoles and other
      larger organelles increased. An acid phosphatase assay confirmed that the
      addition of BFA significantly inhibited secretory pathways. Importantly, Fourier
      transform infrared microspectroscopy documented significant changes in the cell
      wall composition of pollen tubes growing in the presence of BFA. These results
      suggest that enhanced endocytosis, together with inhibited secretion, is
      responsible for the retarded growth of pollen tubes induced by BFA.

PMID- 16299177
TI  - Arabidopsis calcium-dependent protein kinase AtCPK32 interacts with ABF4, a
      transcriptional regulator of abscisic acid-responsive gene expression, and
      modulates its activity.
AB  - The phytohormone abscisic acid (ABA) regulates stress-responsive gene expression
      during vegetative growth. The ABA regulation of many genes is mediated by a
      subfamily of basic leucine zipper class transcription factors referred to as ABFs
      (i.e. ABF1-ABF4), whose transcriptional activity is induced by ABA. Here we show
      that a calcium-dependent protein kinase is involved in the ABA-dependent
      activation process. We carried out yeast two-hybrid screens to identify
      regulatory components of ABF4 function and isolated AtCPK32 as an ABF4
      interacting protein. AtCPK32 has autophosphorylation activity and can
      phosphorylate ABF4 in vitro. Mutational analysis indicated that serine-110 of
      ABF4, which is highly conserved among ABF family members, may be phosphorylated
      by AtCPK32. The serine-110 residue is essential for ABF4-AtCPK32 interaction, and
      transient expression assay revealed that it is also required for the normal
      transcriptional function of ABF4. The expression patterns and subcellular
      localization of AtCPK32 are similar to those of ABF4. Furthermore, its
      overexpression affects both ABA sensitivity and the expression of a number of
      ABF4-regulated genes. Together, our data demonstrate that AtCPK32 is an ABA
      signaling component that regulates the ABA-responsive gene expression via ABF4.

PMID- 16299178
TI  - The diphenylether herbicide lactofen induces cell death and expression of defense
      related genes in soybean.
AB  - Lactofen belongs to the diphenylether class of herbicides, which targets
      protoporphyrinogen oxidase, which in turn causes singlet oxygen generation. In
      tolerant plants like soybean (Glycine max), the chemical nonetheless causes
      necrotic patches called "bronzing" in contact areas. Here it is shown that such
      bronzing is accompanied by cell death, which was quantified from digital
      microscopic images using Assess Software. Cellular autofluorescence accompanied
      cell death, and a homolog of the cell death marker gene, Hsr203j, was induced by
      lactofen in treated soybean tissues. Thus, this form of chemically induced cell
      death shares some hallmarks of certain types of programmed cell death. In
      addition to the cell death phenotype, lactofen caused enhanced expressions of
      chalcone synthase and chalcone reductase genes, mainly in the exposed and
      immediately adjacent (proximal) cells. Furthermore, isoflavone synthase genes,
      which are wound inducible in soybean, were up-regulated by lactofen in both
      proximal and distal cell zones in minimally wounded cotyledons and further
      enhanced in wounded tissues. Moreover, if the wall glucan elicitor from
      Phytophthora sojae was present during lactofen treatment, the induction of
      isoflavone synthase was even more rapid. These results are consistent with the
      fact that lactofen triggers massive isoflavone accumulations and activates the
      capacity for glyceollin elicitation competency. In addition, lactofen induces
      late expression of a selective set of pathogenesis-related (PR) protein genes,
      including PR-1a, PR-5, and PR-10, mainly in treated proximal tissues. These
      various results are discussed in the context of singlet oxygen-induced responses
      and lactofen's potential as a disease resistance-inducing agent.

PMID- 16299179
TI  - Induction of thioredoxin is required for nodule development to reduce reactive
      oxygen species levels in soybean roots.
AB  - Nodules are formed on legume roots as a result of signaling between symbiotic
      partners and in response to the activities of numerous genes. We cloned fragments
      of differentially expressed genes in spot-inoculated soybean (Glycine max) roots.
      Many of the induced clones were similar to known genes related to oxidative
      stress, such as thioredoxin and beta-carotene hydroxylase. The deduced amino acid
      sequences of full-length soybean cDNAs for thioredoxin and beta-carotene
      hydroxylase were similar to those in other species. In situ RNA hybridization
      revealed that the thioredoxin gene is expressed on the pericycle of 2-d-old
      nodules and in the infected cells of mature nodules, suggesting that thioredoxin
      is involved in nodule development. The thioredoxin promoter was found to contain
      a sequence resembling an antioxidant responsive element. When a thioredoxin
      mutant of yeast was transformed with the soybean thioredoxin gene it became
      hydrogen peroxide tolerant. These observations prompted us to measure reactive
      oxygen species levels. These were decreased by 3- to 5-fold in 7-d-old and 27-d
      old nodules, coincident with increases in the expression of thioredoxin and beta
      carotene hydroxylase genes. Hydrogen peroxide-producing regions identified with
      cerium chloride were found in uninoculated roots and 2-d-old nodules, but not in
      7-d-old and 27-d-old nodules. RNA interference-mediated repression of the
      thioredoxin gene severely impaired nodule development. These data indicate that
      antioxidants such as thioredoxin are essential to lower reactive oxygen species
      levels during nodule development.

PMID- 16299180
TI  - Heat stability of maize endosperm ADP-glucose pyrophosphorylase is enhanced by
      insertion of a cysteine in the N terminus of the small subunit.
AB  - ADP-glucose pyrophosphorylase (AGPase) is a key regulatory enzyme in starch
      biosynthesis. However, plant AGPases differ in several parameters, including
      spatial and temporal expression, allosteric regulation, and heat stability.
      AGPases of cereal endosperms are heat labile, while those in other tissues, such
      as the potato (Solanum tuberosum) tuber, are heat stable. Sequence comparisons of
      heat-stable and heat-labile AGPases identified an N-terminal motif unique to heat
      stable enzymes. Insertion of this motif into recombinant maize (Zea mays)
      endosperm AGPase increased the half-life at 58 degrees C more than 70-fold. Km
      values for physiological substrates were unaffected, although Kcat was doubled. A
      cysteine within the inserted motif gives rise to small subunit homodimers not
      found in the wild-type maize enzyme. Placement of this N-terminal motif into a
      mosaic small subunit containing the N terminus from maize endosperm and the C
      terminus from potato tuber AGPase increases heat stability more than 300-fold.

PMID- 16299181
TI  - Analysis of the female gametophyte transcriptome of Arabidopsis by comparative
      expression profiling.
AB  - The extensive data on the transcription of the plant genome are derived primarily
      from the sporophytic generation. There currently is little information on genes
      that are expressed during female gametophyte development in angiosperms, and it
      is not known whether the female gametophyte transcriptome contains a major set of
      genes that are not expressed in the sporophyte or whether it is primarily a
      subset of the sporophytic transcriptome. Because the embryo sac is embedded
      within the maternal ovule tissue, we have utilized the Arabidopsis (Arabidopsis
      thaliana) mutant sporocyteless that produces ovules without embryo sacs, together
      with the ATH1 Arabidopsis whole-genome oligonucleotide array, to identify genes
      that are preferentially or specifically expressed in female gametophyte
      development. From analysis of the datasets, 225 genes are identified as female
      gametophyte genes, likely a lower limit as stringent criteria were used for the
      analysis, eliminating many low expressed genes. Nearly 45% of the identified
      genes were not previously detected by sporophytic expression profiling,
      suggesting that the embryo sac transcriptome may contain a significant fraction
      of transcripts restricted to the gametophyte. Validation of six candidate genes
      was performed using promoterbeta-glucuronidase fusions, and all of these showed
      embryo sac-specific expression in the ovule. The unfiltered expression data from
      this study can be used to evaluate the possibility of female gametophytic
      expression for any gene in the ATH1 array, and contribute to identification of
      the functions of the component of the Arabidopsis genome not represented in
      studies of sporophytic expression and function.

PMID- 16299182
TI  - At5PTase13 modulates cotyledon vein development through regulating auxin
      homeostasis.
AB  - Phosphatidylinositol signaling pathway and the relevant metabolites are known to
      be critical to the modulation of different aspects of plant growth, development,
      and stress responses. Inositol polyphosphate 5-phosphatase is a key enzyme
      involved in phosphatidylinositol metabolism and is encoded by an At5PTase gene
      family in Arabidopsis thaliana. A previous study shows that At5PTase11 mediates
      cotyledon vascular development probably through the regulation of intracellular
      calcium levels. In this study, we provide evidence that At5PTase13 modulates the
      development of cotyledon veins through its regulation of auxin homeostasis. A T
      DNA insertional knockout mutant, At5pt13-1, showed a defect in development of the
      cotyledon vein, which was rescued completely by exogenous auxin and in part by
      brassinolide, a steroid hormone. Furthermore, the mutant had reduced auxin
      content and altered auxin accumulation in seedlings revealed by the DR5:beta
      glucuronidase fusion construct in seedlings. In addition, microarray analysis
      shows that the transcription of key genes responsible for auxin biosynthesis and
      transport was altered in At5pt13-1. The At5pt13-1 mutant was also less sensitive
      to auxin inhibition of root elongation. These results suggest that At5PTase13
      regulates the homeostasis of auxin, a key hormone controlling vascular
      development in plants.

PMID- 16299183
TI  - A cellular timetable of autumn senescence.
AB  - We have studied autumn leaf senescence in a free-growing aspen (Populus tremula)
      by following changes in pigment, metabolite and nutrient content, photosynthesis,
      and cell and organelle integrity. The senescence process started on September 11,
      2003, apparently initiated solely by the photoperiod, and progressed steadily
      without any obvious influence of other environmental signals. For example, after
      this date, senescing leaves accumulated anthocyanins in response to conditions
      inducing photooxidative stress, but at the beginning of September the leaves did
      not. Degradation of leaf constituents took place over an 18-d period, and,
      although the cells in each leaf did not all senesce in parallel, senescence in
      the tree as a whole was synchronous. Lutein and beta-carotene were degraded in
      parallel with chlorophyll, whereas neoxanthin and the xanthophyll cycle pigments
      were retained longer. Chloroplasts in each cell were rapidly converted to
      gerontoplasts and many, although not all, cells died. From September 19, when
      chlorophyll levels had dropped by 50%, mitochondrial respiration provided the
      energy for nutrient remobilization. Remobilization seemed to stop on September
      29, probably due to the cessation of phloem transport, but, up to abscission of
      the last leaves (over 1 week later), some cells were metabolically active and had
      chlorophyll-containing gerontoplasts. About 80% of the nitrogen and phosphorus
      was remobilized, and on September 29 a sudden change occurred in the delta15N of
      the cellular content, indicating that volatile compounds may have been released.

PMID- 16299184
TI  - Sucrose-specific induction of anthocyanin biosynthesis in Arabidopsis requires
      the MYB75/PAP1 gene.
AB  - Sugar-induced anthocyanin accumulation has been observed in many plant species.
      We observed that sucrose (Suc) is the most effective inducer of anthocyanin
      biosynthesis in Arabidopsis (Arabidopsis thaliana) seedlings. Other sugars and
      osmotic controls are either less effective or ineffective. Analysis of Suc
      induced anthocyanin accumulation in 43 Arabidopsis accessions shows that
      considerable natural variation exists for this trait. The Cape Verde Islands
      (Cvi) accession essentially does not respond to Suc, whereas Landsberg erecta is
      an intermediate responder. The existing Landsberg erecta/Cvi recombinant inbred
      line population was used in a quantitative trait loci analysis for Suc-induced
      anthocyanin accumulation (SIAA). A total of four quantitative trait loci for SIAA
      were identified in this way. The locus with the largest contribution to the
      trait, SIAA1, was fine mapped and using a candidate gene approach, it was shown
      that the MYB75/PAP1 gene encodes SIAA1. Genetic complementation studies and
      analysis of a laboratory-generated knockout mutation in this gene confirmed this
      conclusion. Suc, in a concentration-dependent way, induces MYB75/PAP1 mRNA
      accumulation. Moreover, MYB75/PAP1 is essential for the Suc-mediated expression
      of the dihydroflavonol reductase gene. The SIAA1 locus in Cvi probably is a weak
      or loss-of-function MYB75/PAP1 allele. The C24 accession similarly shows a very
      weak response to Suc-induced anthocyanin accumulation encoded by the same locus.
      Sequence analysis showed that the Cvi and C24 accessions harbor mutations both
      inside and downstream of the DNA-binding domain of the MYB75/PAP1 protein, which
      most likely result in loss of activity.

PMID- 16299185
TI  - A wound-responsive and phospholipid-regulated maize calcium-dependent protein
      kinase.
AB  - Using protein sequence data obtained from a calcium- and phospholipid-regulated
      protein kinase purified from maize (Zea mays), we isolated a cDNA encoding a
      calcium-dependent protein kinase (CDPK), which we designated ZmCPK11. The deduced
      amino acid sequence of ZmCPK11 includes the sequences of all the peptides
      obtained from the native protein. The ZmCPK11 sequence contains the kinase,
      autoregulatory, and calmodulin-like domains typical of CDPKs. Transcripts for
      ZmCPK11 were present in every tested organ of the plant, relatively high in seeds
      and seedlings and lower in stems, roots, and leaves. In leaves, kinase activity
      and ZmCPK11 mRNA accumulation were stimulated by wounding. The level of ZmCPK11
      is also increased in noninjured neighboring leaves. The results suggest that the
      maize protein kinase is involved in a systemic response to wounding. Bacterially
      expressed glutathione S-transferase (GST)-ZmCPK11 was catalytically active in a
      calcium-dependent manner. Like the native enzyme, GST-ZmCPK11 was able to
      phosphorylate histone III-S and Syntide 2. Phosphorylation of histone was
      stimulated by phosphatidylserine, phosphatidylinositol, and phosphatidic acid,
      whereas phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine,
      diolein, and cardiolipin did not increase the enzymatic activity.
      Autophosphorylation of GST-ZmCPK11 was stimulated by calcium and by phosphatidic
      acid and, to a lesser extent, by phosphatidylserine. Phosphatidylcholine did not
      affect autophosphorylation. These data unequivocally identify the maize
      phospholipid- and calcium-regulated protein kinase, which has protein kinase C
      like activity, as a CDPK, and emphasize the potential that other CDPKs are
      regulated by phospholipids in addition to calcium.

PMID- 16299186
TI  - Evaluation of the antimicrobial activities of plant oxylipins supports their
      involvement in defense against pathogens.
AB  - Plant oxylipins are a large family of metabolites derived from polyunsaturated
      fatty acids. The characterization of mutants or transgenic plants affected in the
      biosynthesis or perception of oxylipins has recently emphasized the role of the
      so-called oxylipin pathway in plant defense against pests and pathogens. In this
      context, presumed functions of oxylipins include direct antimicrobial effect,
      stimulation of plant defense gene expression, and regulation of plant cell death.
      However, the precise contribution of individual oxylipins to plant defense
      remains essentially unknown. To get a better insight into the biological
      activities of oxylipins, in vitro growth inhibition assays were used to
      investigate the direct antimicrobial activities of 43 natural oxylipins against a
      set of 13 plant pathogenic microorganisms including bacteria, oomycetes, and
      fungi. This study showed unequivocally that most oxylipins are able to impair
      growth of some plant microbial pathogens, with only two out of 43 oxylipins being
      completely inactive against all the tested organisms, and 26 oxylipins showing
      inhibitory activity toward at least three different microbes. Six oxylipins
      strongly inhibited mycelial growth and spore germination of eukaryotic microbes,
      including compounds that had not previously been ascribed an antimicrobial
      activity, such as 13-keto-9(Z),11(E),15(Z)-octadecatrienoic acid and 12-oxo
      10,15(Z)-phytodienoic acid. Interestingly, this first large-scale comparative
      assessment of the antimicrobial effects of oxylipins reveals that regulators of
      plant defense responses are also the most active oxylipins against eukaryotic
      microorganisms, suggesting that such oxylipins might contribute to plant defense
      through their effects both on the plant and on pathogens, possibly through
      related mechanisms.

PMID- 16299187
TI  - Microarray analysis of lipopolysaccharide potentiation of trovafloxacin-induced
      liver injury in rats suggests a role for proinflammatory chemokines and
      neutrophils.
AB  - Idiosyncratic drug toxicity refers to toxic reactions occurring in a small subset
      of patients and usually cannot be predicted during preclinical or early phases of
      clinical trials. One hypothesis for the pathogenesis of hepatic idiosyncratic
      drug reactions is that, in certain individuals, underlying inflammation results
      in sensitization of the liver, such that injury occurs from an agent that
      typically would not cause hepatotoxicity at a therapeutic dose. We explored this
      possibility by cotreating rats with nonhepatotoxic doses of bacterial
      lipopolysaccharide (LPS) and trovafloxacin (TVX), a drug that caused
      idiosyncratic hepatotoxicity in humans. The combination of LPS and TVX resulted
      in hepatotoxicity in rats, as determined by increases in serum alanine
      aminotransferase activity and hepatocellular necrosis, which were not observed
      with either agent alone. In contrast, treatment with LPS and levofloxacin, a
      fluoroquinolone without human idiosyncratic liability, did not result in these
      changes. Liver gene expression analysis identified unique changes induced by the
      combination of TVX and LPS, including enhanced expression of chemokines,
      suggestive of liver neutrophil (PMN) accumulation and activation. Consistent with
      a role for PMN in the hepatotoxicity induced by LPS/TVX, prior depletion of PMN
      attenuated the liver injury. The results suggest that gene expression profiles
      predictive of idiosyncratic liability can be generated in rats cotreated with LPS
      and drug. Furthermore, they identify gene expression changes that could be
      explored as biomarkers for idiosyncratic toxicity and lead to enhanced
      understanding of the mechanism(s) underlying hepatotoxicity induced by TVX.

PMID- 16299188
TI  - Estrogen receptor alpha mediates acute potassium channel stimulation in human
      coronary artery smooth muscle cells.
AB  - The pleiotropic effects of estrogen are mediated via stimulation of two estrogen
      receptor (ER) subtypes, ERalpha and ERbeta. Although a number of studies have
      identified expression of one or both subtypes in estrogen target tissues, fewer
      studies have correlated ER expression with a functional role of these proteins in
      regulating cellular excitability. In the present study, we have combined cellular
      fluorescence, immunocytochemistry, and molecular expression techniques with
      single-channel patch-clamp studies to determine which ER mediates estrogen
      stimulated potassium channel activity in human coronary artery smooth muscle
      cells (HCASMC). We had demonstrated previously that estrogen stimulates activity
      of the large-conductance, calcium- and voltage-activated potassium (BK(Ca))
      channel in HCASMC via a nongenomic mechanism. We now demonstrate expression of
      both ERalpha and ERbeta subtypes in HCASMC. Functionally, however, expression of
      ERalpha antisense plasmid abolished the acute effect of estrogen on these
      channels, whereas estrogen retained its ability to stimulate BK(Ca) channels in
      cells transfected with only green fluorescence protein. In contrast,
      overexpression of ERalpha enhanced the stimulatory action of estrogen in HCASMC.
      Transfection with ERalpha antisense/sense plasmid did not alter ERbeta
      expression. These findings indicate that the ERalpha isoform mediates estrogen
      induced stimulation of BK(Ca) channels in HCASMC and thereby provide evidence for
      a receptor-dependent signaling mechanism that can mediate estrogen-induced
      inhibition of cellular excitability.

PMID- 16299189
TI  - Detection of coins ingested by children using a handheld metal detector: a
      systematic review.
AB  - To determine if the use of a handheld metal detector (HHMD) can safely reduce the
      number of radiographs requested in cases of coins ingested by children, a search
      was performed to identify prospective studies of the ability of an HHMD to
      identify the presence or absence of ingested coin in children (17 years or
      younger). Outcome measures were presence or absence of coin on metal detector
      screening, and accuracy of coin localisation. Inclusion and exclusion criteria
      were defined. Mantel-Haenszel (fixed effect model) pooling with 95% confidence
      intervals (CI) was used to calculate overall sensitivities and specificities. In
      total, 11 studies met the inclusion criteria. The overall sensitivity of the HHMD
      at detecting the presence of coins was 99.4% (95% CI 98.0 to 99.9%) and accuracy
      at localisation was 99.8% (98.5 to 100.0%). The overall specificity of the HHMD
      was 100% (76.8 to 100%). Use of the HHMD is an accurate, radiation free, and cost
      effective method of identifying and localising coins ingested by children. An
      algorithm for investigating children with coin ingestion is proposed.

PMID- 16299190
TI  - Head injuries: a study evaluating the impact of the NICE head injury guidelines.
AB  - BACKGROUND: The NICE head injury guidelines recommend a different approach in the
      management of head injury patients. It suggests that CT head scan should replace
      skull x ray (SXR) and observation/admission as the first investigation. We wished
      to determine the impact of NICE on SXR, CT scan, and admission on all patients
      with head injury presenting to the ED setting and estimate the cost effectiveness
      of these guidelines, which has not been quantified to date. DESIGN: Study of head
      injury patients presenting to two EDs before and after implementation of NICE
      guidelines METHODS: The rate of SXR, CT scan, and admission were determined six
      months before and one month after NICE implementation in both centres. The before
      study also looked at predicted rates had NICE been applied. This enabled
      predicted and actual cost effectiveness to be determined. RESULT: 1130 patients
      with head injury were studied in four 1 month periods (two in each centre). At
      the teaching hospital, the CT head scan rate more than doubled (3% to 7%), the
      SXR declined (37% to 4%), while the admission rate more than halved (9% to 4%).
      This represented a saving of 3381 pounds sterling per 100 head injury PATIENTS:
      greater than predicted with no adverse events. At the District General Hospital,
      the CT head scan rate more than quadrupled (1.4% to 9%), the SXR dropped (19 to
      0.57%), while the admission rate declined (7% to 5%). This represented a saving
      of 290 pounds sterling per 100 head injury patients: less than predicted.
      CONCLUSION: The implementation of the NICE guidelines led to a two to fivefold
      increase in the CT head scan rate depending on the cases and baseline
      departmental practice. However, the reduction in SXR and admission appears to
      more than offset these costs without compromising patient outcomes.

PMID- 16299191
TI  - An audit of clinical practice in the management of head injured patients
      following the introduction of the Scottish Intercollegiate Guidelines Network
      (SIGN) recommendations.
AB  - A prospective study was conducted by the Scottish Trauma Audit Group (STAG) in
      A&E of Edinburgh Royal Infirmary to examine clinical practices in the management
      of head injured patients pre- and post-inception of the SIGN guidelines published
      in August 2000.1607 patients attended the department in two separate one month
      periods at equal intervals pre- and post-guidelines publication. The majority of
      patients with a SIGN indication for admission were admitted (93% pre- and 92%
      post-guidelines). For skull x ray (SXR) requests, in the pre-guidelines group,
      92% of admitted patients with a SIGN indication for x ray had a SXR: this figure
      dropped to 79% post-guidelines. 36% of patients with a SIGN indication for CT
      actually had a scan pre-guidelines: this figure increased to 64% post
      guidelines.57% of patients pre-guidelines and 44% of patients post-guidelines
      were discharged from A&E in accordance with the SIGN recommendations. Of patients
      admitted for neurological observations, this increased from 50% pre- to 88% post
      guidelines. Of patients who were discharged "inappropriately", only one re
      presented and was subsequently admitted but required no neurosurgical
      intervention. Despite publication of the SIGN guidelines and positive
      reinforcement in A&E and at ward level, practice has not changed significantly.
      Where our practice did not adhere to SIGN recommendations, there was no untoward
      sequelae. For published national guidelines to be effective, a formal audit
      structure with regular feedback is necessary to ensure a continued change in
      clinical practices.

PMID- 16299192
TI  - Derivation of a clinical decision rule to guide the interhospital transfer of
      patients with blunt traumatic brain injury.
AB  - OBJECTIVE: To derive a clinical decision rule for people with traumatic brain
      injury (TBI) that enables early identification of patients requiring specialised
      trauma care. METHODS: We collected data from 1999 through 2003 on a retrospective
      cohort of consecutive people aged 18-65 years with a serious head injury (AIS >
      or =3), transported directly from the scene of injury, and evaluated in the ED.
      Information on 22 demographical, physiological, radiographic, and lab variables
      was collected. Resource based "high therapeutic intensity" measures occurring
      within 72 hours of ED arrival (the outcome measure) were identified a priori and
      included: neurosurgical intervention, exploratory laparotomy, intensive care
      interventions, or death. We used classification and regression tree analysis to
      derive and cross validate the decision rule. RESULTS: 504 consecutive trauma
      patients were identified as having a serious head injury: 246 (49%) required at
      least one of the HTI measures. Five ED variables (GCS, respiratory rate, age,
      temperature, and pulse rate) identified subjects requiring at least one of the
      HTI measures with 94% sensitivity (95% CI 91 to 97%) and 63% specificity (95% CI
      57 to 69%) in the derivation sample, and 90% sensitivity and 55% specificity
      using cross validation. CONCLUSIONS: This decision rule identified among a cohort
      of head injured patients evaluated in the ED the majority of those who urgently
      required specialised trauma care. The rule will require prospective validation in
      injured people presenting to non-tertiary care hospitals before implementation
      can be recommended.

PMID- 16299193
TI  - Are we able to comply with the NICE head injury guidelines?
AB  - BACKGROUND: An estimated 120,000 patients are admitted to hospital in England and
      Wales each year for neurological observations following a head injury. The
      National Institute for Clinical Excellence (NICE) has issued guidelines on the
      quality and frequency of neurological observations that should be made.
      OBJECTIVE: Review of frequency and quality of observations in one trauma unit.
      STUDY DESIGN: Prospective audit of current practice. METHOD: Data on 100
      consecutive patients admitted to a trauma unit for neurological observations were
      audited to monitor the consistency and frequency of neurological observations
      requested by the admitting doctor. Medical staff had previously been briefed on
      the recommendations of the NICE head injury guidelines. RESULTS: A detailed
      evaluation revealed inconsistency and inexplicable gaps in observations. No
      single set of observations was complete. Sequential regular monitoring was
      difficult for many reasons, bringing into question the safety and reliability of
      current practice. CONCLUSIONS: The introduction of the new guidelines which
      recommend more frequent neurological observations has major staffing
      implications, where underperformance raises significant clinical governance
      issues. All hospitals admitting patients with head injuries should have an
      established protocol based on the NICE guidelines with observations recorded on
      an appropriately designed data collection form. Trained nursing staff have
      enormous work and time pressures including direct patient care, ward rounds, drug
      rounds, administration, management, and responding to emergencies. The
      development of a competency based training programme for auxiliary nursing staff
      to undertake neurological observations, including when to report concerns, is one
      solution to reduce the pressure on trained nursing staff.

PMID- 16299194
TI  - Has the assessment of isolated ankle injuries altered since 1993?
AB  - BACKGROUND: Performance of emergency departments in England and Wales has
      declined in recent years. Data from the authors' department has shown that junior
      doctors now see fewer patients and spend longer over their assessment than was
      the case previously. This study aimed to determine how the assessment of patients
      with isolated ankle injuries changed over an 11 year period. METHODS: A
      retrospective case note review was conducted. Data regarding the duration of
      assessment, clinical information recorded, investigations, and treatments were
      retrieved. RESULTS: During the period studied 13 555 patients presented with
      isolated ankle injuries; case notes of 550 of these patients were reviewed in the
      present study. Linear regression demonstrated that the median length of time from
      arrival in the department until seen by a clinician increased (b = 3.0 min/year,
      95% CI 0.7 to 5.2, p = 0.015), but the median length of time from seeing a
      clinician until leaving the department was unchanged (b = 0.6 min/year, 95% CI 
      1.3 to 2.5, p = 0.475). More clinical information was being recorded, but the
      proportion of patients having radiographs of the ankle (b = 0.24% per year, 95%
      CI -1.40% to 1.87%, p = 0.751) or in whom a fracture was diagnosed (b = -0.20%
      per year, 95% CI -1.59% to 1.19% per year, p = 0.752) remained unchanged.
      CONCLUSION: It appears from this study that the duration of assessment of
      patients with minor injuries is not changing although this result should be
      interpreted cautiously.

PMID- 16299195
TI  - Relationship between Trendelenburg tilt and internal jugular vein diameter.
AB  - OBJECTIVES: To evaluate the relationship between Trendelenburg tilt and internal
      jugular vein (IJV) diameter, and to examine any cumulative effects of tilt on the
      IJV diameter. METHODS: Using a tilt table, healthy volunteers were randomised to
      Trendelenburg tilts of 10 degrees, 15 degrees, 20 degrees, 25 degrees, and 30
      degrees. Ultrasound was used to measure and record the lateral diameter of the
      right IJV at the level of the cricoid cartilage. Following each reading the table
      was returned to the supine position. Balanced randomisation was used to assess
      cumulative tilt effects. RESULTS: A total of 20 healthy volunteers were recruited
      (10 men, 10 women). Mean supine IJV diameter was 13.5 mm (95% CI 12.8 to 14.1)
      and was significantly greater at 10 degrees (15.5 mm, 95% CI 14.9 to 16.1). There
      was no significant difference between 10 degrees and greater angles of tilt. The
      effect of the previous angle of tilt did not prove to be statistically
      significant. CONCLUSION: Increasing the degree of Trendelenburg tilt increases
      the lateral diameter of the IJV. Even a 10 degrees tilt is effective. The
      cumulative effect of tilt (that is, the effect of the previous angle) is not
      significant. Ultrasound guided cannulation is ideal, but in its absence
      Trendelenburg tilt will increase IJV diameter and improve the chance of
      successful cannulation. While 25 degrees achieved optimum distension, this may
      not be practical and may be detrimental (for example, risk of raised intracranial
      pressure).

PMID- 16299196
TI  - Jehovah's Witnesses in the emergency department: what are their rights?
AB  - The Jehovah's Witnesses Society is best known to outsiders for its refusal of
      blood products, even when such a refusal may result in death. Since the
      introduction of the blood ban in 1945, Jehovah's Witness (JW) parents have fought
      for their rights to refuse blood on behalf of their children, based on religious
      beliefs and their right to raise children as they see fit. Adolescent JWs have
      also sought to refuse blood products based on their beliefs, regardless of the
      views of their parents. Adult JWs have fought to protect their autonomy when
      making both contemporaneous and advance treatment refusal. The refusal of blood
      products by JWs raises ethical and legal dilemmas that are not easily answered.
      Do an individual's rights (namely bodily control, right to privacy, right to
      decide about life/death issues, right to religious freedom) outweigh society's
      rights (namely the preservation of life, the prevention of suicide, the
      protection of innocent third parties, and the maintenance of the ethical
      integrity of the medical profession)? Does the right to choose outweigh the value
      of human life? For doctors, conflict occurs between the desire to respect patient
      autonomy and the need to provide good medical care. The Watchtower Society (the
      JW governing body) imposes a strict code of moral standards among its members,
      and it is unlikely that individual JWs are making truly autonomous decisions
      about blood transfusions. While young children and adolescents are protected by
      the courts and conscious adults are afforded autonomy, dilemmas still arise in
      the emergency situation. This article examines the rights of young children,
      adolescents, and adults, focusing in the latter half on adults in the emergency
      situation.

PMID- 16299197
TI  - Prevalence and healthcare burden of illegal drug use among emergency department
      patients.
AB  - OBJECTIVES: Illegal drug use is common in emergency department (ED) patients, but
      previous prevalence studies have relied upon approaches that may underestimate
      the true extent of the problem. The aim of this study was to examine illegal drug
      use in a typical adult ED. METHODS: We employed an independent researcher to
      prospectively and anonymously interview patients attending an inner city adult ED
      throughout all 168 hours of a typical week. Additional information collected from
      the treating clinician indicated whether each presentation was directly or
      indirectly related to illegal drug use. RESULTS: We found that 6.9% of all
      patient attendances were directly or indirectly related to illegal drug use, and
      hospital admission was required in nearly half of these. The majority of drug
      related problems were acute injuries, overdose, and the medical complications of
      drug use. CONCLUSIONS: This suggests that the emergency healthcare burden related
      to illegal drug use is substantial, and higher than previously reported.

PMID- 16299198
TI  - The effect of blunt abdominal trauma on appendix vermiformis.
AB  - OBJECTIVES: Trauma and appendicitis are the most common conditions of childhood
      for which surgical consultation is sought in emergency departments. Occasionally,
      appendicitis and trauma exist together, which causes an interesting debate
      whether trauma has led to appendicitis. We aimed to evaluate our patients with
      traumatic appendicitis and to discuss their properties in the light of the
      literature. METHODS: We retrospectively reviewed the charts of children of blunt
      abdominal trauma accompanied by appendicitis. RESULTS: Of 29 cases of blunt
      abdominal trauma that had required surgical exploration, five were found to have
      gross findings of acute appendicitis and underwent appendicectomy. Appendicitis
      was confirmed histopathologically. CONCLUSION: It should be kept in mind that
      children managed for severe blunt abdominal trauma may develop appendicitis. If
      clinical outlook suggests appendicitis in cases conservatively managed for blunt
      abdominal trauma, physical examinations, abdominal ultrasonography and/or
      abdominal computed tomography should be repeated for diagnosis of traumatic
      appendicitis. This approach will help to protect the patients against the
      complications of appendicitis that are likely to develop.

PMID- 16299199
TI  - Nine cases of accidental exposure to dimethyl sulphate--a potential chemical
      weapon.
AB  - Dimethyl sulphate (DMS) is an innocuous appearing, widely used, and highly toxic
      chemical. It is used both as a methylating agent in industrial chemical synthesis
      and in medical laboratories for chemical cleavage of DNA. It is readily absorbed
      through the skin, mucous membranes, and gastrointestinal tract. Delayed toxicity
      allows potentially fatal exposures to occur prior to development of any warning
      symptoms. Toxicity is manifested initially by mucosal inflammation of eyes, nose,
      oropharynx, and airways. This can progress to severe airway oedema and necrosis,
      and non-cardiogenic pulmonary oedema. Other systemic effects include convulsions,
      delirium, coma, and renal, hepatic, and cardiac failure. All these features make
      DMS a potential chemical weapon. We report nine cases of varying degrees of
      inhalational exposure to DMS, occurring as a result of a single chemical spillage
      incident in the United Kingdom. Industrial poisoning is surprisingly rare and
      there are few previous reports in the literature outside China.

PMID- 16299200
TI  - Toxicity of maduramicin.
AB  - This report documents the first presentation of seven human cases of poisoning
      with a compound used in poultry feed. The clinical presentation was a toxic
      polyneuropathy with rhabdomyolysis and acute renal failure. We describe the
      protracted clinical course of one of these victims along with a tabulated
      description of the clinical course and relevant laboratory investigations of the
      others.

PMID- 16299201
TI  - Prospective audit of 106 consecutive human bite injuries: the importance of
      history taking.
AB  - OBJECTIVES: Some patients attempt to conceal human bites with factitious
      mechanisms of injury. Follow up questioning allows patients to modify their
      histories. This practice was prospectively audited. METHODS: Patients with
      cutaneous wounds who did not present with a history of human bite were asked a
      follow up question. Those who then gave a history of human bite were noted.
      RESULTS: Certain groups of patients with human bites were significantly more
      likely to provide a factitious history and/or delay presentation. CONCLUSION:
      Follow up questioning dramatically increased the case-detection rate, prompting
      specific management.

PMID- 16299202
TI  - Reduction of the posterior pelvic ring by non-invasive stabilisation: a report of
      two cases.
AB  - We demonstrate radiological evidence that an external pelvic splint is effective
      at reducing open book pelvic fractures. Its use in the pre-hospital and emergency
      department settings should be encouraged in the initial management and
      resuscitation of patients with pelvic fractures.

PMID- 16299204
TI  - Best evidence topic report. Towards evidence based emergency medicine: best BETs
      from the Manchester Royal Infirmary.

PMID- 16299203
TI  - Best evidence topic report. Prehospital endotracheal intubation in adult major
      trauma patients with head injury.
AB  - A short cut review was carried out to establish whether prehospital intubation
      was of benefit to patients with moderate to severe head injury. 4630 papers were
      found using the reported searches, of which 9 presented the best evidence to
      answer the clinical question. The author, date and country of publication,
      patient group studied, study type, relevant outcomes, results, and study
      weaknesses of these best papers are tabulated. It is concluded that prehospital
      intubation is associated with increased mortality in these patients.

PMID- 16299205
TI  - Best evidence topic report. S-100b protein levels as a predictor for long-term
      disability after head injury.
AB  - A short cut review was carried out to establish whether levels of S-100b were
      predictive of long-term disability after head injury. 200 papers were found using
      the reported searches, of which 12 presented the best evidence to answer the
      clinical question. The author, date, and country of publication, patient group
      studied, study type, relevant outcomes, results and study weaknesses of these
      best papers are tabulated. It is concluded that a raised level of S-100b is a
      marker of poorer long-term outcome after both major and minor head injury.

PMID- 16299207
TI  - Best evidence topic report. Aspirin and the risk of intracranial complications
      following head injury.
AB  - A short cut review was carried out to establish whether pre-injury aspirin
      increases the risk of intracranial complications following head injury. 124
      papers were found using the reported searches, of which three presented the best
      evidence to answer the clinical question. The author, date, and country of
      publication, patient group studied, study type, relevant outcomes, results, and
      study weaknesses of these best papers are tabulated. It is concluded that aspirin
      may increase the risk of developing intracranial complications. More research is
      needed.

PMID- 16299206
TI  - Best evidence topic report. Headache in paediatric head injury.
AB  - A short cut review was carried out to establish whether headache was a
      significant indicator of the severity of head injury in children. 301 papers were
      found using the reported searches, of which 2 presented the best evidence to
      answer the clinical question. The author, date, and country of publication,
      patient group studied, study type, relevant outcomes, results, and study
      weaknesses of these best papers are tabulated. It is concluded that headache is
      not an independent risk factor for intracranial injury in children.

PMID- 16299208
TI  - Pre-hospital emergency care in Ireland.

PMID- 16299209
TI  - BASICS Conference 2005.

PMID- 16299210
TI  - Setting the scene for the paramedic in primary care: a review of the literature.
AB  - Recognition of the paramedic "profession" began in 2003, with the introduction of
      statutory registration and the promotion of graduate entry. This paper explores
      the published evidence which surrounds paramedic practice in an attempt to
      identify the skills, training, and professional capacity which paramedics of the
      future will require. A systematic analysis was carried out of key reviews and
      commentaries published between January 1995 and April 2004, and informal
      discussions with experts and researchers in the field were undertaken. There
      remains little high quality published evidence with which to validate many
      aspects of current paramedic practice. To keep pace with service developments,
      paramedic training must embrace the complexities of autonomous practice.
      Undoubtedly in the short term, paramedics must be taught to appropriately
      identify and manage a far wider range of commonly occurring conditions, minor
      illnesses, and trauma. However, in the longer term, and more importantly,
      paramedics must learn to work together to take ownership of the basic
      philosophies of their practice, which must have their foundation in valid and
      reliable research.

PMID- 16299211
TI  - A systematic review of the safety of analgesia with 50% nitrous oxide: can lay
      responders use analgesic gases in the prehospital setting?
AB  - A safe and effective form of pain relief would be an advantage in the prehospital
      treatment of patients experiencing extreme pain. Although used by many emergency
      medical services, 50% nitrous oxide (an inhaled analgesic known to have good pain
      relief properties) is not widely used by volunteer and semiprofessional
      organisations. This review aimed to determine whether 50% nitrous oxide is safe
      for use by first responders who are not trained as emergency medical technicians.
      A thorough search of the literature identified 12 randomised controlled trials
      investigating the use of 50% nitrous oxide (as compared with placebo or
      conventional analgesic regimens) in a range of conditions. The outcomes analysed
      for this review were: adverse events, recovery time, and need for additional
      medication. None of the studies compared the treatments in the prehospital
      setting; children were well represented. Adverse effects were rare and
      significant adverse outcomes such as hypotension and oxygen desaturation could
      not be attributed to nitrous oxide. Compared with patients receiving conventional
      analgesia, those receiving 50% nitrous oxide did not require additional
      medication any more frequently and had a faster recovery from sedative effects.
      The low incidence of significant adverse events from 50% nitrous oxide suggests
      that this agent could be used safely by lay responders.

PMID- 16299212
TI  - Assessment of the "nearly normal" cervical spine radiograph: C2-C3
      pseudosubluxation in an adult with whiplash injury.
AB  - C2-C3 pseudosubluxation is a well recognized normal anatomical variant in
      children and this physiological spondylolisthesis often makes the interpretation
      of paediatric cervical spine radiographs difficult. In direct contrast, this
      finding is rare in adults and has not been reported as a diagnostic difficulty
      following neck injury. We report a case of C2-C3 pseudosubluxation occurring in a
      27 year old woman presenting with neck pain 1 week after a road traffic accident.
      Although there are effective radiological guidelines for cervical spine
      radiograph evaluation in children, there is no evidence that these can be applied
      to the adult cervical spine. Flexion and extension cervical spine views have
      limitations. In such cases, magnetic resonance imaging is required to
      definitively exclude pathological injury.

PMID- 16299213
TI  - A case of familial third ventricular colloid cyst.
AB  - Colloid cyst of the third ventricle is a rare benign intracranial lesion, and
      familial cases are rarer still. They may be asymptomatic or present with symptoms
      of raised intracranial pressure, including sudden death. Surgical excision is
      curative. We report a 24 year old pregnant woman with familial colloid cyst, who
      presented with headaches and suffered a cardiorespiratory arrest. Early computed
      tomography scan of the brain is advised in patients with a family history of
      third ventricular colloid cyst presenting to the accident and emergency
      department with headache.

PMID- 16299214
TI  - Spontaneous coronary artery dissection.
AB  - Spontaneous coronary artery dissection is a rare cause of myocardial ischaemia or
      sudden death, predominantly affecting young women with no known risk factors for
      cardiovascular disease. The case described emphasises the benefit of early
      diagnosis and the need to individualise management based on patient response to
      treatment.

PMID- 16299215
TI  - Look before you pack: key point in epistaxis management.
AB  - We report a patient with epistaxis who used cotton wool to pack his nose before
      reaching the hospital, and underwent further packing in the accident and
      emergency department, which probably pushed the cottonwool further back. This led
      to the formation of foreign body granuloma inside the nasal cavity. It is
      difficult to examine the nose without proper equipment and experience, and the
      examination is more difficult in the presence of active bleeding to find a
      foreign body such as cotton wool. Hence, it is important to ask the patient about
      any temporary pack they have used in the nose and to look for and remove it
      before inserting a proper pack. It is also important for trainees to have a
      better understanding of the different levels of management of epistaxis. Hence,
      we propose the term "epistaxis management ladder" for easy understanding of the
      treatment of epistaxis.

PMID- 16299216
TI  - Cardiac luxation: an unusual complication of a log roll.
AB  - Cardiac luxation is a rare but potentially fatal consequence of blunt thoracic
      trauma. We present a case of a pericardial tear with cardiac luxation following
      blunt chest trauma. It is hypothesised that the cardiac luxation occurred while
      log rolling the patient during the initial assessment. This report stresses the
      need to be aware of the potential for such a complication.

PMID- 16299217
TI  - Rupture of the tibialis posterior tendon: an important differential in the
      assessment of ankle injuries.
AB  - Rupture of the tibialis posterior tendon can be missed. We report a case of
      posterior tibialis tendon rupture that, owing to misdiagnosis, resulted in a
      significant foot deformity requiring arthrodesis for chronic pain.

PMID- 16299218
TI  - Stab to second intercostal space: a bubbling extrapleural wound.
AB  - A 37 year old man was found collapsed at the roadside and taken to the emergency
      department. Communication was difficult, as the patient could not speak English.
      There was a wound in the left second intercostal space on the midclavicular line,
      which was bleeding and was bubbling air. A drain was inserted, bleeding
      controlled, and his wounds sutured. Chest x ray later confirmed satisfactory
      placement of the drain. The following day, swelling and discharge indicated
      oesophageal damage, which was later confirmed by gastrografin swallow. With
      conservative management in hospital for 2 weeks, he made a full recovery and was
      discharged.

PMID- 16299219
TI  - Abdominal pain and dysuria in pregnancy: urinary tract infection or life
      threatening haemorrhage?
AB  - This report describes the case of a 27 year old woman presenting at 19 weeks'
      gestation with epigastric pain and dysuria. Initially diagnosed with a urinary
      tract infection, she re-presented 10 days later with acute abdominal pain and
      haemoperitoneum. The diagnosis of placenta percreta was not made until
      laparotomy. This case highlights placenta percreta as a rare but serious
      complication of pregnancy that may become increasingly frequent as the rates of
      caesarean delivery rise. Early diagnosis, close monitoring, and prompt surgical
      management are essential as massive blood loss can occur. This can be
      challenging, as clinical presentation can be unusual.

PMID- 16299220
TI  - Tension empyema as a reversible cause for cardiac arrest.
AB  - Empyema is a well recognised complication of pneumonia.1 We report a case of
      pulseless electrical activity (PEA) treated in the emergency department (ED) with
      intercostal tube drainage based on clinical findings, where a tension empyema was
      found to be the cause. To our knowledge, this is the first report of actual
      cardiac arrest from this cause.

PMID- 16299221
TI  - A case of perilymphatic fistula in blunt head injury.
AB  - Dizziness is a common symptom following blunt head injury. This is usually
      attributed to the "post-concussive" syndrome. Here we present a patient whose
      symptoms following head injury were a result of him having developed a
      perilymphatic fistula.

PMID- 16299222
TI  - Monitoring junior doctors after a major incident.

PMID- 16299224
TI  - Irrational exuberance in clinical proteomics.

PMID- 16299223
TI  - Sugars and circadian regulation make major contributions to the global regulation
      of diurnal gene expression in Arabidopsis.
AB  - The diurnal cycle strongly influences many plant metabolic and physiological
      processes. Arabidopsis thaliana rosettes were harvested six times during 12-h
      light/12-h-dark treatments to investigate changes in gene expression using ATH1
      arrays. Diagnostic gene sets were identified from published or in-house
      expression profiles of the response to light, sugar, nitrogen, and water deficit
      in seedlings and 4 h of darkness or illumination at ambient or compensation point
      [CO(2)]. Many sugar-responsive genes showed large diurnal expression changes,
      whose timing matched that of the diurnal changes of sugars. A set of circadian
      regulated genes also showed large diurnal changes in expression. Comparison of
      published results from a free-running cycle with the diurnal changes in Columbia
      0 (Col-0) and the starchless phosphoglucomutase (pgm) mutant indicated that
      sugars modify the expression of up to half of the clock-regulated genes.
      Principle component analysis identified genes that make large contributions to
      diurnal changes and confirmed that sugar and circadian regulation are the major
      inputs in Col-0 but that sugars dominate the response in pgm. Most of the changes
      in pgm are triggered by low sugar levels during the night rather than high levels
      in the light, highlighting the importance of responses to low sugar in diurnal
      gene regulation. We identified a set of candidate regulatory genes that show
      robust responses to alterations in sugar levels and change markedly during the
      diurnal cycle.

PMID- 16299225
TI  - Phosphatidylinositol 3-kinase inhibitors are a triple threat to ovarian cancer.

PMID- 16299226
TI  - The progress and promise of molecular imaging probes in oncologic drug
      development.
AB  - As addressed by the recent Food and Drug Administration Critical Path Initiative,
      tools are urgently needed to increase the speed, efficiency, and cost
      effectiveness of drug development for cancer and other diseases. Molecular
      imaging probes developed based on recent scientific advances have great potential
      as oncologic drug development tools. Basic science studies using molecular
      imaging probes can help to identify and characterize disease-specific targets for
      oncologic drug therapy. Imaging end points, based on these disease-specific
      biomarkers, hold great promise to better define, stratify, and enrich study
      groups and to provide direct biological measures of response. Imaging-based
      biomarkers also have promise for speeding drug evaluation by supplementing or
      replacing preclinical and clinical pharmacokinetic and pharmacodynamic
      evaluations, including target interaction and modulation. Such analyses may be
      particularly valuable in early comparative studies among candidates designed to
      interact with the same molecular target. Finally, as response biomarkers, imaging
      end points that characterize tumor vitality, growth, or apoptosis can also serve
      as early surrogates of therapy success. This article outlines the scientific
      basis of oncology imaging probes and presents examples of probes that could
      facilitate progress. The current regulatory opportunities for new and existing
      probe development and testing are also reviewed, with a focus on recent Food and
      Drug Administration guidance to facilitate early clinical development of
      promising probes.

PMID- 16299227
TI  - Clear cell sarcoma of the kidney: up-regulation of neural markers with activation
      of the sonic hedgehog and Akt pathways.
AB  - PURPOSE AND EXPERIMENTAL DESIGN: Clear cell sarcoma of the kidney (CCSK), the
      second most common renal tumor in children, poses significant diagnostic
      challenges. No positive diagnostic markers are available, and the pathogenesis of
      CCSK remains an enigma. To address these challenges, the gene expression patterns
      of 14 CCSKs were compared with 15 Wilms tumors and 3 fetal kidney samples using
      oligonucleotide arrays. RESULTS: Using unsupervised methods, the gene expression
      profile of CCSK was distinctive: differentially expressed genes could largely be
      grouped into four categories: (a) a wide variety of neural markers, (b) members
      of the Sonic hedgehog pathway, (c) members of the phosphoinositide-3-kinase/Akt
      cell proliferation pathway, and (d) known therapeutic targets. Corresponding
      changes in critical proteins using Western blot and/or immunohistochemistry
      confirmed the up-regulation of these pathways and proteins. In particular, CD117
      and epidermal growth factor receptor are up-regulated at the protein level in
      many CCSKs, providing potential therapeutic targets. One of the neural markers,
      nerve growth factor receptor, represents a promising diagnostic tool for CCSK.
      CONCLUSIONS: This study suggests that CCSKs arise within a renal mesenchymal cell
      that shows a wide variety of neural markers. As such, it seems to be susceptible
      to genetic changes also seen in a variety of other neuroectodermal and neuronal
      tumors, including activation of Sonic hedgehog and phosphoinositide-3-kinase/Akt
      pathways. Involvement of these pathways in CCSKs implicates their widening role
      in tumorigenesis.

PMID- 16299228
TI  - Heparanase is involved in angiogenesis in esophageal cancer through induction of
      cyclooxygenase-2.
AB  - PURPOSE: Both heparanase and cyclooxygenase-2 (COX-2) are thought to play
      critical roles for tumor malignancy, including angiogenesis, although it is
      unknown about their relationship with each other in cancer progression. We
      hypothesized that they may link to each other on tumor angiogenesis. EXPERIMENTAL
      DESIGN: The expressions of heparanase and COX-2 in 77 primary human esophageal
      cancer tissues were assessed by immunohistochemistry to do statistical analysis
      for the correlation between their clinicopathologic features, microvessel
      density, and survival of those clinical cases. Human esophageal cancer cells were
      transduced with heparanase cDNA and used for reverse transcription-PCR and
      Western blot to determine the expression of heparanase and COX-2. COX-2 promoter
      vector and its deletion/mutation constructs were also used along with
      transduction of heparanase cDNA for luciferase assay. RESULTS: Heparanase and COX
      2 protein expression exhibited a similar pattern in esophageal tumor tissues, and
      their expression correlated with tumor malignancy and poor survival. Their
      expression also revealed a significant correlation with high intratumoral
      microvessel density. Up-regulation of COX-2 mRNA and protein was observed in
      esophageal cancer cells transfected with heparanase cDNA. COX-2 promoter was
      activated after heparanase cDNA was transduced and the deletion/mutation of three
      transcription factor (cyclic AMP response element, nuclear factor-kappaB, and
      nuclear factor-interleukin-6) binding elements in COX-2 promoter strongly
      suppressed its activity. CONCLUSION: Our results suggest that heparanase may play
      a novel role for COX-2-mediated tumor angiogenesis.

PMID- 16299229
TI  - Changes in cytoskeletal protein composition indicative of an epithelial
      mesenchymal transition in human micrometastatic and primary breast carcinoma
      cells.
AB  - PURPOSE: The bone marrow is a frequent and clinically important homing site for
      early disseminated breast cancer cells. Here, we aimed to profile the protein
      expression of these cells using unique cell line models and to evaluate the
      prognostic relevance of candidate gene expression for breast cancer patients.
      EXPERIMENTAL DESIGN: To identify expression patterns characteristic for
      micrometastatic cells, three different cell lines (BC-K1, BC-P1, and BC-S1)
      established by SV40 immortalization of cancer cells isolated from the bone marrow
      of patients with breast cancer were compared with MCF-7 breast cancer and SV40
      immortalized normal breast ductal cells (MTSV-1.7) using two-dimensional gel
      electrophoresis followed by MALDI-ToF analysis. The prognostic significance and
      clinicopathologic associations of selected differentially expressed proteins were
      evaluated using high-density breast cancer tissue microarrays. RESULTS: In
      contrast to MCF-7 and MTSV1-7 reference cell lines, all micrometastatic cancer
      cell lines displayed loss of epithelial cytokeratins (CK8, CK18, and CK19) and
      ectopic expression of vimentin commonly present in mesenchymal cells.
      Immunohistochemical analysis of 2,517 samples of breast cancer further showed
      that loss of cytokeratin and ectopic vimentin expression were significantly
      associated with a higher tumor grade, high mitotic index, and negative
      estrogen/progesterone-receptor status. Although in univariate analyses
      significantly related to clinical outcome, none of the cytokeratins analyzed were
      independently associated with either overall or cancer-specific survival.
      CONCLUSIONS: Micrometastatic cancer cells exhibit marked changes in the
      expression pattern of cytoskeletal proteins indicative of an epithelial
      mesenchymal transition. This phenotypical change could already be detected in
      primary tumors and is associated with the aggressive behavior of breast cancer
      cells in vivo.

PMID- 16299230
TI  - Androgen mediation of thrombocytosis in epithelial ovarian cancer biology.
AB  - PURPOSE: Preoperative thrombocytosis (platelet count > 400 x 10(9)/L) at initial
      exploration for epithelial ovarian carcinoma is associated with decreased
      surgical cytoreducibility and poor survival. Platelets express androgen receptor
      (AR), which contains a polymorphic CAG trinucleotide repeat sequence of which the
      length inversely correlates with AR transactivation function. We hypothesized
      that androgen-mediated thrombocytosis promotes aggressive ovarian cancer biology.
      EXPERIMENTAL DESIGN: Sixty-three patients with epithelial ovarian carcinoma
      underwent genotype analysis of the CAG repeat polymorphism in AR. Medical records
      were reviewed to assess preoperative thrombocytosis, surgical findings, and
      survival. Data were examined using the Fisher's exact, logistic regression, and
      Kaplan-Meier analyses. RESULTS: AR CAG repeat lengths ranged from 8 to 27, with a
      median of 23. Fifteen of 63 patients (23.8%) showed preoperative thrombocytosis.
      Short AR allelotype (< or = 20 CAG repeats) was associated with a higher
      incidence of thrombocytosis (P = 0.04). The combination of short AR allelotype
      and thrombocytosis was the only significant factor that predicted inability to
      achieve optimal surgical cytoreduction (P = 0.02). Women with short AR allelotype
      and thrombocytosis showed statistically decreased progression-free survival (13
      versus 37 months, P = 0.01) and overall survival (37 versus 65 months, P = 0.02)
      when compared with women with long AR allelotype and normal platelet counts. On
      multivariate analyses, suboptimal cytoreduction was the only significant factor
      predictive of disease-specific overall survival (P = 0.0002) but the combination
      of short AR allelotype and thrombocytosis approached statistical significance (P
      = 0.08). CONCLUSIONS: Androgen modulation of thrombocytosis may promote
      aggressive epithelial ovarian cancer biology.

PMID- 16299231
TI  - Overexpression of the cytokine osteopontin identifies aggressive laryngeal
      squamous cell carcinomas and enhances carcinoma cell proliferation and
      invasiveness.
AB  - PURPOSE: Osteopontin is a secreted cytokine that binds to the cell surface CD44v6
      receptor. We studied osteopontin and CD44v6 expression in laryngeal squamous cell
      carcinomas and correlated osteopontin expression levels with clinicopathologic
      tumor features. EXPERIMENTAL DESIGN: We used immunohistochemistry,
      immunoblotting, and reverse transcription-PCR to study osteopontin expression in
      58 laryngeal squamous cell carcinomas. Cultured squamous carcinoma cells were
      treated with exogenous osteopontin or with RNA interference to knockdown
      osteopontin expression. RESULTS: Osteopontin expression was higher in all the
      invasive carcinomas than in patient-matched normal mucosa. Its expression levels
      were significantly correlated with tumor stage and grade and with the presence of
      lymph node and distant metastases. Osteopontin positivity was negatively
      correlated with overall survival (P = 0.03). Osteopontin expression was
      paralleled by intense cell surface reactivity for CD44v6. Treatment of squamous
      carcinoma cells with recombinant osteopontin sharply increased proliferation and
      Matrigel invasion in comparison with the untreated cells parallel to activation
      of the mitogen-activated protein kinase/extracellular signal-regulated kinase
      kinase/mitogen-activated protein kinase signaling cascade. Osteopontin knockdown
      by RNA interference, anti-CD44 antibodies, and mitogen-activated protein
      kinase/extracellular signal-regulated kinase kinase inhibition prevented these
      effects. CONCLUSIONS: These results identify osteopontin as a marker and a
      potential therapeutic target in cases of aggressive laryngeal squamous cell
      carcinomas.

PMID- 16299232
TI  - Estrogen signaling is active in cartilaginous tumors: implications for
      antiestrogen therapy as treatment option of metastasized or irresectable
      chondrosarcoma.
AB  - PURPOSE: Chondrosarcoma is a malignant cartilaginous matrix-producing tumor that
      can be lethal in 10% to 50% of the patients. Surgery is the only effective
      treatment known as these tumors are notorious refractory to all types of
      conventional chemotherapy or radiotherapy. To identify a target for therapy, we
      want to determine whether estrogen signaling is active in chondrosarcoma because
      estrogen is important in the regulation of longitudinal growth that is initiated
      by chondrocyte proliferation and differentiation in the epiphyseal growth plate
      of long bones. EXPERIMENTAL DESIGN: We studied protein expression of the estrogen
      receptor in 35 cartilaginous tumors as well as mRNA levels for the estrogen
      receptor and for aromatase, an enzyme for estrogen synthesis and another
      potential therapeutic target. Furthermore, the activity of aromatase was
      determined in vitro by the tritiated water release assay. Dose-response
      experiments with chondrosarcoma cultured cells were done with estrogen,
      androstenedione, and exemestane. RESULTS: All chondrosarcomas tested showed mRNA
      and nuclear protein expression of the estrogen receptor. Also, aromatase mRNA was
      detected. The aromatase activity assay showed a functional aromatase enzyme in
      primary chondrosarcoma cultures and in a cell line. Growth of chondrosarcoma cell
      cultures can be stimulated by adding estrogen or androstenedione, which can be
      inhibited by exemestane. CONCLUSIONS: These results show, on the RNA, protein,
      and cell biological levels, that the ligand and the receptor are active in
      estrogen-mediated signal transduction. This observation implicates potential use
      of targeted drugs that interfere with estrogen signaling, such as those applied
      for treating breast cancer.

PMID- 16299233
TI  - Positive correlation between estradiol and vascular endothelial growth factor but
      not fibroblast growth factor-2 in normal human breast tissue in vivo.
AB  - PURPOSE: Angiogenesis is crucial in tumor development and progression. Ovarian
      hormones regulate angiogenesis in the reproductive tract but very little is known
      about its regulation in the normal breast. Sex steroids play an important role in
      breast cancer development by poorly understood mechanisms. Vascular endothelial
      growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) are potent
      stimulators of angiogenesis. Both VEGF and FGF-2 function in autocrine/paracrine
      pathways and there is a major contribution of bioactive proteins by a
      posttranslational activation of sequestered molecules in the extracellular space.
      A direct measurement of these molecules in the extracellular compartment is,
      therefore, needed. EXPERIMENTAL DESIGN: In this study, microdialysis was used to
      measure extracellular VEGF and FGF-2 in normal human breast tissue in situ in 11
      premenopausal and 5 postmenopausal women. RESULTS: Significantly higher level of
      VEGF in breast tissue of premenopausal women was found. Plasma as well as local
      estradiol and breast tissue VEGF exhibited significant correlations, whereas
      progesterone had no correlation with breast VEGF. FGF-2 did not correlate with
      either estradiol or progesterone. CONCLUSION: The result suggests that estradiol
      is a more potent regulator of free VEGF levels than progesterone in the normal
      breast. The control of free FGF-2 seems to be independent of sex steroids in the
      breast. Estrogen induction of free extracellular VEGF may be one mechanism
      involved in sex steroid-dependent breast carcinogenesis.

PMID- 16299234
TI  - Possible prediction of chemoradiosensitivity of esophageal cancer by serum
      protein profiling.
AB  - PURPOSE: Establishment of a reliable method of predicting the efficacy of
      chemotherapy and radiotherapy is necessary to provide the most suitable treatment
      for each cancer patient. We investigated whether proteomic profiles of serum
      samples obtained from untreated patients were capable of being used to predict
      the efficacy of combined preoperative chemoradiotherapy against esophageal
      cancer. EXPERIMENTAL DESIGN: Proteomic spectra were obtained from a training set
      of 27 serum samples (15 pathologically diagnosed responders to preoperative
      chemoradiotherapy and 12 nonresponders) by surface-enhanced laser desorption and
      ionization coupled with hybrid quadrupole time-of-flight mass spectrometry. A
      proteomic pattern prediction model was constructed from the training set by
      machine learning algorithms, and it was then tested with an independent
      validation set consisting of serum samples from 15 esophageal cancer patients in
      a blinded manner. RESULTS: We selected a set of four mass peaks, at 7,420, 9,112,
      17,123, and 12,867 m/z, from a total of 859 protein peaks, as perfectly
      distinguishing responders from nonresponders in the training set with a support
      vector machine algorithm. This set of peaks (i.e., the classifier) correctly
      diagnosed chemoradiosensitivity in 93.3% (14 of 15) of the cases in the
      validation set. CONCLUSIONS: Recent mass spectrometric approaches have revealed
      that serum contains a large volume of information that reflects the
      microenvironment of diseased organs. Although a multi-institutional large-scale
      study will be necessary to confirm each component of the classifier, there is a
      subtle but definite difference in serum proteomic profile between responders and
      nonresponders to chemoradiotherapy.

PMID- 16299235
TI  - Specialized DNA arrays for the differentiation of pancreatic tumors.
AB  - PURPOSE: Malignant tumors of the pancreas are frequently indistinguishable from
      inflammatory tumors arising in the context of a chronic pancreatitis with the use
      of conventional imaging techniques. Thus, cytologic analysis of cells obtained by
      abdominal ultrasound, computed tomography, or endoscopic ultrasound-guided fine
      needle aspiration biopsy is required for diagnosis. However, the reliability of
      cytologic analyses of pancreatic fine needle aspirates remains unsatisfactory,
      with a diagnostic accuracy of < or =80%. The purpose of the current study was
      therefore to develop a novel diagnostic approach based on expression profiling of
      biopsy material using a specialized diagnostic cDNA array. EXPERIMENTAL DESIGN:
      Previous gene expression profiling studies were reevaluated to design a 558
      feature diagnostic array. Minimal amounts of residual material from pancreatic
      cytology samples as well as surgically resected tumor and control tissue
      specimens were analyzed using the diagnostic array and a newly developed
      statistical classification system. RESULTS AND CONCLUSIONS: Our diagnostic
      approach resulted in 95% accurate differentiation between ductal adenocarcinomas
      and nonmalignant tumors of the pancreas. The diagnostic array, in conjunction
      with conventional diagnostic procedures, is thus suitable to significantly
      improve the reliability of pancreatic cancer diagnostics and can be expected to
      become a valuable new tool in the routine workup of suspect masses in the
      pancreas.

PMID- 16299236
TI  - Cancer-testis genes are coordinately expressed and are markers of poor outcome in
      non-small cell lung cancer.
AB  - PURPOSE: Cancer-testis genes mapping to the X chromosome have common expression
      patterns and show similar responses to modulators of epigenetic mechanisms. We
      asked whether cancer-testis gene expression occurred coordinately, and whether it
      correlated with variables of disease and clinical outcome of non-small cell lung
      cancer (NSCLC). EXPERIMENTAL DESIGN: Tumors from 523 NSCLC patients undergoing
      surgery were evaluated for the expression of nine cancer-testis genes (NY-ESO-1,
      LAGE-1, MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, CT7/MAGE-C1, SSX2, and SSX4) by
      semiquantitative PCR. Clinical data available for 447 patients were used to
      correlate cancer-testis expression to variables of disease and clinical outcome.
      RESULTS: At least one cancer-testis gene was expressed by 90% of squamous
      carcinoma, 62% of bronchioloalveolar cancer, and 67% of adenocarcinoma samples.
      Statistically significant coexpression was observed for 34 of the 36 possible
      cancer-testis combinations. Cancer-testis gene expression, either cumulatively or
      individually, showed significant associations with male sex, smoking history,
      advanced tumor, nodal and pathologic stages, pleural invasion, and the absence of
      ground glass opacity. Cox regression analysis revealed the expression of NY-ESO-1
      and MAGE-A3 as markers of poor prognosis, independent of confounding variables
      for adenocarcinoma of the lung. CONCLUSIONS: Cancer-testis genes are coordinately
      expressed in NSCLC, and their expression is associated with advanced disease and
      poor outcome.

PMID- 16299237
TI  - Increased expression of vascular endothelial growth factor C in papillary thyroid
      carcinoma correlates with cervical lymph node metastases.
AB  - PURPOSE: Despite recent studies showing that vascular endothelial growth factor C
      (VEGF-C) mRNA is up-regulated in papillary thyroid carcinoma (PTC), the role of
      VEGF-C in lymph node metastasis is still unclear. The aim of this study is to
      investigate the expression pattern of VEGF-C immunoreactive protein in PTC and
      its relationship with cervical lymph node metastasis. EXPERIMENTAL DESIGN: Tissue
      samples were obtained from 39 specimens of PTC (20 with and 19 without lymph node
      metastasis) as well as 20 benign thyroid nodules. Overexpression of the VEGF-C
      protein was evaluated by immunoblotting with specific anti-VEGF-C antibody in
      paired tumor and nontumor tissues from PTC. The data were compared with patients'
      clinicopathologic features and lymph node metastasis. Immunohistochemical
      staining was done on selected paraffin sections to determine cellular
      localization of VEGF-C and to assess flt-4 (or VEGFR-3)-positive vessel density
      in PTC lesions. RESULTS: Overexpression of VEGF-C was detected in 69% of the PTC
      and in 5% of the benign thyroid specimens. When comparing between the metastatic
      and nonmetastatic groups of PTC, a higher expression level of VEGF-C was detected
      in both the tumor (P = 0.004) and adjacent nontumor tissues (P = 0.011). Positive
      immunostaining for VEGF-C was confirmed in PTC tumor tissues and metastatic lymph
      nodes, which correlated with flt-4-positive vessel density in tumor and peritumor
      tissues. The increased expression of VEGF-C protein in PTC is associated with
      lymph node metastasis (P = 0.004) and lymphovascular permeation (P = 0.001) but
      is independent of other clinicopatholgic variables. CONCLUSIONS: The VEGF-C
      immunoreactive protein is overexpressed in PTC lesions, which correlates with
      lymph node metastases. VEGF-C expression may play a role in lymphangiogenesis of
      PTC and further study is necessary to evaluate the clinical application of VEGF-C
      as a molecular marker for tumor metastases to cervical lymph nodes.

PMID- 16299238
TI  - Transcription repressor slug promotes carcinoma invasion and predicts outcome of
      patients with lung adenocarcinoma.
AB  - PURPOSE: In a previous genome-wide gene expression profiling analysis using an
      invasion cancer cell lines model, we have identified Slug as selectively
      overexpressed in the highly invasive cancer cells. Here, we investigated the
      clinical significance of Slug in lung adenocarcinoma and the role of Slug in the
      process of cancer cell invasion and metastasis. EXPERIMENTAL DESIGN: Real-time
      quantitative reverse transcription-PCR was used to investigate Slug mRNA in
      surgically resected lung adenocarcinoma of 54 patients and its correlation with
      survival. We overexpressed Slug in a lung adenocarcinoma cell line with very low
      Slug levels and investigated the in vitro and in vivo effects of Slug expression.
      RESULTS: High expression of Slug mRNA in lung cancer tissue was significantly
      associated with postoperative relapse (P = 0.03) and shorter patient survival (P
      < 0.001). The overexpression of Slug enhanced xenograft tumor growth and
      increased microvessel counts in angiogenesis assay. Both inducible and
      constitutive overexpression of Slug suppressed the expression of E-cadherin and
      increased the in vitro invasive ability. Zymography revealed increased matrix
      metalloproteinase-2 activity in Slug overexpressed cells. ELISA, reverse
      transcription-PCR, and immunohistochemistry confirmed the increase of matrix
      metalloproteinase-2 proteins and mRNA in Slug overexpressed cells and xenograft
      tumors. CONCLUSIONS: Slug expression can predict the clinical outcome of lung
      adenocarcinoma patients. Slug is a novel invasion-promoting gene in lung
      adenocarcinoma.

PMID- 16299239
TI  - Highly sensitive detection of melanoma at an early stage based on the increased
      serum secreted protein acidic and rich in cysteine and glypican-3 levels.
AB  - PURPOSE: There are no available tumor markers detecting primary melanoma at an
      early stage. The identification of such serum markers would be of significant
      benefit for an early diagnosis of melanoma. We recently identified glypican-3
      (GPC3) as a novel tumor marker but could diagnose only 40% of melanomas. Thereby,
      we focused out attention on secreted protein acidic and rich in cysteine (SPARC)
      overexpressed in melanoma as another candidate for tumor marker. EXPERIMENTAL
      DESIGN: Secreted SPARC protein was quantified using ELISA in the sera from 109
      melanoma patients, five patients with large congenital melanocytic nevus, 61 age
      matched healthy donors, and 13 disease-free patients after undergoing a surgical
      removal. We also quantified GPC3 and 5-S-cysteinyldopa in the same serum samples
      and compared these markers for their diagnostic value. RESULTS: The serum SPARC
      concentrations in melanoma patients were greater than those in healthy donors (P
      = 0.001). When we fixed a cutoff value at the mean concentration plus 2 SD of the
      healthy donors, the serum SPARC was found to have increased in the sera of 36 of
      the 109 (33%) melanoma patients, whereas there were three (4.9%) false-positive
      cases of 61 healthy donors. Surprisingly, 19 of 36 patients showing increased
      SPARC levels were in stages 0 to II. The serum SPARC level decreased under the
      cutoff level in 10 of 13 patients after surgical removal. Using SPARC and GPC3 in
      combination thus enabled us to diagnose 47 of 75 (66.2%) melanoma patients at an
      early stage (0-II). CONCLUSIONS: SPARC or its combination with GPC3 is thus
      considered a potentially useful tumor marker, especially for melanoma at an early
      stage.

PMID- 16299240
TI  - Phase II trial of oral aminopterin for adults and children with refractory acute
      leukemia.
AB  - PURPOSE: To determine the antileukemic activity of weekly oral aminopterin in
      patients with refractory acute leukemia; to describe the pharmacodynamic
      properties of aminopterin; and to contrast the intracellular metabolism of
      aminopterin and methotrexate by patients' blasts in vitro. EXPERIMENTAL DESIGN:
      Forty-six patients were enrolled in three strata: children with acute
      lymphoblastic leukemia (ALL), adults with ALL, and patients with acute myeloid
      leukemia (AML). Aminopterin was given weekly, in two doses of 2 mg/m(2), 12 hours
      apart. Limited sampling pharmacokinetic analysis was done during the first week
      of therapy. Accumulation of [(3)H]aminopterin and [(3)H]methotrexate by leukemic
      blasts was studied in vitro. RESULTS: Six of 22 children with ALL (27%; 95%
      confidence interval, 8-47%) had clinically significant responses. None of those
      with AML and only two of 11 adults with ALL had responses meeting protocol
      definitions, although peripheral blast counts tended to decrease with therapy in
      all groups. Mucosal toxicity was minimal, even with limited use of leucovorin
      rescue. Complete bioavailability of aminopterin was confirmed, with a mean area
      under the curve of 0.52 +/- 0.03 micromol hour/L after oral dosing. No
      relationship between aminopterin pharmacokinetics and response was seen. In
      vitro, aminopterin showed more consistent metabolism by leukemic blasts to
      polyglutamates than methotrexate. Lineage-specific differences in the pattern of
      intracellular antifolylpolyglutamates were observed. CONCLUSIONS: Weekly oral
      aminopterin has significant activity among children with refractory ALL. With
      greater cellular accumulation and metabolism, more reliable bioavailability than
      methotrexate, and tolerable toxicity at this dose and schedule, aminopterin
      deserves further study as a potent alternative to methotrexate.

PMID- 16299242
TI  - Response of some head and neck cancers to epidermal growth factor receptor
      tyrosine kinase inhibitors may be linked to mutation of ERBB2 rather than EGFR.
AB  - PURPOSE: Small-molecule tyrosine kinase inhibitors (TKI) of the epidermal growth
      factor receptor (EGFR) have shown modest yet reproducible response rates in
      patients with squamous cell carcinoma of the head and neck (SCCHN). Somatic
      mutations in EGFR have recently been shown to be predictive of a clinical
      response in patients with non-small cell lung cancer (NSCLC) treated with these
      inhibitors. The objective of this study was to determine if such mutations, or
      recently reported mutations in ERBB2, also underlie EGFR-TKI responsiveness in
      SCCHN patients. EXPERIMENTAL DESIGN: We sequenced the kinase domain of EGFR and
      exon 20 of ERBB2 in tumor specimens from eight responsive patients. In addition,
      mutational analysis was done on tumor specimens from nine gefitinib nonresponders
      and 65 unselected cases of SCCHN. RESULTS: None of eight TKI-responsive specimens
      had mutations within the kinase domain of EGFR. EGFR amplification was also not
      associated with drug responsiveness. However, a single responsive case had a
      somatic missense mutation within exon 20 of ERBB2. CONCLUSION: Our data indicate
      that unlike NSCLC, EGFR kinase mutations are rare in unselected cases of SCCHN
      within the United States and are not linked to gefitinib or erlotinib responses
      in SCCHN. Alternative mechanisms, including ERBB2 mutations, may underlie
      responsiveness in this tumor type.

PMID- 16299241
TI  - Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 polymorphisms with the
      pharmacokinetics of paclitaxel.
AB  - PURPOSE: To retrospectively evaluate the effects of six known allelic variants in
      the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes on the pharmacokinetics of the
      anticancer agent paclitaxel (Taxol). EXPERIMENTAL DESIGN: A cohort of 97
      Caucasian patients with cancer (median age, 57 years) received paclitaxel as an
      i.v. infusion (dose range, 80-225 mg/m(2)). Genomic DNA was analyzed using PCR
      RFLP or using Pyrosequencing. Pharmacokinetic variables for unbound paclitaxel
      were estimated using nonlinear mixed effect modeling. The effects of genotypes on
      typical value of clearance were evaluated with the likelihood ratio test within
      NONMEM. In addition, relations between genotype and individual pharmacokinetic
      variable estimates were evaluated with one-way ANOVA. RESULTS: The allele
      frequencies for the CYP2C8*2, CYP2C8*3, CYP2C8*4, CYP3A4*3, CYP3A5*3C, and ABCB1
      3435C>T variants were 0.7%, 9.2%, 2.1%, 0.5%, 93.2%, and 47.1%, respectively, and
      all were in Hardy-Weinberg equilibrium. The population typical value of clearance
      of unbound paclitaxel was 301 L/h (individual clearance range, 83.7-1055 L/h).
      The CYP2C8 or CYP3A4/5 genotypes were not statistically significantly associated
      with unbound clearance of paclitaxel. Likewise, no statistically significant
      association was observed between the ABCB1 3435C>T variant and any of the studied
      pharmacokinetic variables. CONCLUSIONS: This study indicates that the presently
      evaluated variant alleles in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes do not
      explain the substantial interindividual variability in paclitaxel
      pharmacokinetics.

PMID- 16299243
TI  - Predictors of prostate cancer tissue acquisition by an undirected core bone
      marrow biopsy in metastatic castration-resistant prostate cancer--a Cancer and
      Leukemia Group B study.
AB  - PURPOSE: Analyzing metastatic prostate cancer tissue is of considerable
      importance in evaluating new targeted agents, yet acquiring such tissue presents
      a challenge due to the predominance of bone metastases. We assessed factors
      predicting a successful tumor harvest from bone marrow biopsies (BMBx) in
      castration-resistant metastatic prostate cancer patients. MATERIAL AND METHODS:
      Data from Cancer and Leukemia Group B study 9663 were reviewed. Bone marrow
      biopsies were obtained from 184 patients who underwent an office-based, unguided
      bone marrow biopsy of the posterior iliac crest. RESULTS: Forty-seven of the 184
      patients (25.5%) had a positive bone marrow biopsy. When considered in a
      multivariate logistic regression analysis, lower hemoglobin levels, higher
      alkaline phosphatase, and higher lactate dehydrogenase levels were associated
      with a higher likelihood of a positive BMBx. The median survival time was 11
      months (95% confidence interval, 8.0-14) among patients with a positive BMBx
      compared with 23 months (95% confidence interval, 19-27) with a negative BMBx.
      The median time to progression and time to prostate-specific antigen progression
      free survival were also significantly decreased among positive BMBx patients. No
      patients with a positive BMBx survived beyond 3 years, whereas 11 of the 137
      patients with a negative BMBx survived beyond 5 years. DISCUSSION: Using common
      laboratory values, a specific patient cohort can be defined from whom the yield
      of a nonguided BMBx would be high enough to justify this approach. For studies
      that require broader entry criteria, a more directed approach with image guidance
      is recommended.

PMID- 16299244
TI  - Comparison of two cancer vaccines targeting tyrosinase: plasmid DNA and
      recombinant alphavirus replicon particles.
AB  - PURPOSE: Immunization of mice with xenogeneic DNA encoding human tyrosinase
      related proteins 1 and 2 breaks tolerance to these self-antigens and leads to
      tumor rejection. Viral vectors used alone or in heterologous DNA prime/viral
      boost combinations have shown improved responses to certain infectious diseases.
      The purpose of this study was to compare viral and plasmid DNA in combination
      vaccination strategies in the context of a tumor antigen. EXPERIMENTAL DESIGN:
      Using tyrosinase as a prototypical differentiation antigen, we determined the
      optimal regimen for immunization with plasmid DNA. Then, using propagation
      incompetent alphavirus vectors (virus-like replicon particles, VRP) encoding
      tyrosinase, we tested different combinations of priming with DNA or VRP followed
      by boosting with VRP. We subsequently followed antibody production, T-cell
      response, and tumor rejection. RESULTS: T-cell responses to newly identified
      mouse tyrosinase epitopes were generated in mice immunized with plasmid DNA
      encoding human (xenogeneic) tyrosinase. In contrast, when VRP encoding either
      mouse or human tyrosinase were used as single agents, antibody and T-cell
      responses and a significant delay in tumor growth in vivo were observed.
      Similarly, a heterologous vaccine regimen using DNA prime and VRP boost showed a
      markedly stronger response than DNA vaccination alone. CONCLUSIONS: Alphavirus
      replicon particle vectors encoding the melanoma antigen tyrosinase (self or
      xenogeneic) induce immune responses and tumor protection when administered either
      alone or in the heterologous DNA prime/VRP boost approaches that are superior to
      the use of plasmid DNA alone.

PMID- 16299245
TI  - Inhibition of the met receptor in mesothelioma.
AB  - BACKGROUND: Expression of the Met receptor and its ligand, hepatocyte growth
      factor (HGF), has been observed in 74% to 100% and 40% to 85% of malignant
      pleural mesothelioma (MPM) specimens, respectively. HGF stimulation has been
      shown to enhance MPM cell proliferation, migration, cell scattering, and
      invasiveness. EXPERIMENTAL DESIGN: To investigate a potential therapeutic role
      for the Met receptor in MPM, we examined the effects of PHA-665752, a specific
      small-molecule inhibitor of the Met receptor tyrosine kinase, in a panel of 10
      MPM cell lines. RESULTS: Two of the cell lines, H2461 and JMN-1B, exhibited
      autocrine HGF production as measured by ELISA (3.9 and 10.5 ng/mL, respectively,
      versus <0.05 ng/mL in other cell lines). Evaluation of PHA-665752 across the 10
      MPM cell lines indicated that despite Met expression in all cell lines, only in
      cell lines that exhibited a Met/HGF autocrine loop, H2461 and JMN-1B, did PHA
      665752 inhibit growth with an IC(50) of 1 and 2 micromol/L, respectively. No
      activating mutations in Met were detected in any of the cell lines. Consistent
      with observed growth inhibition, PHA-665752 caused cell cycle arrest at G(1)-S
      boundary accompanied by a dose-dependent decrease in phosphorylation of Met,
      p70S6K, Akt, and extracellular signal-regulated kinase 1/2. Growth of H2461 cells
      was also inhibited by neutralizing antibodies to HGF and by RNA interference
      knockdown of the Met receptor, confirming that growth inhibition observed was
      through a Met-dependent mechanism. PHA-665752 also reduced MPM in vitro cell
      migration and invasion. CONCLUSIONS: Taken together, these findings suggest that
      inhibition of the Met receptor may be an effective therapeutic strategy for
      patients with MPM and provides a mechanism, the presence of a HGF/Met autocrine
      loop, by which to select patients for PHA-665752 treatment.

PMID- 16299246
TI  - Combination bcl-2 antisense and radiation therapy for nasopharyngeal cancer.
AB  - PURPOSE: A wide variety of tumors depend on the dysregulation of Bcl-2 family
      proteins for survival. The resulting apoptotic block can often provide a
      mechanism for resistance to anticancer treatments, such as chemotherapy and
      radiation. This current study evaluates the efficacy of combining systemically
      delivered Bcl-2 phosphorothioate antisense (Bcl-2 ASO) and radiation for
      nasopharyngeal cancer therapy. RESULTS: Antisense uptake was unaffected by 0, 3,
      or 6 Gy radiation. Radiation decreased the fraction of viable C666-1 cells to
      60%, with a further decrease to 40% in combination with Bcl-2 ASO. Despite a
      modest in vitro effect, Bcl-2 ASO alone caused the regression of established
      xenograft tumors in mice, extending survival by 15 days in a C666-1 and by 6 days
      in a C15 model. The survival times for mice treated with both Bcl-2 ASO and
      radiation increased by 52 days in C666-1 and by 20 days in C15 tumors. This
      combination resulted in a more-than-additive effect in C666-1 tumors. Less
      impressive gains observed in C15 tumors might be attributable to higher
      expression of antiapoptotic Bcl-2 family proteins and limited drug distribution
      in the tumor. Retreatment of C666-1 tumors with the Bcl-2 ASO-radiation
      combination, however, was effective, resulting in mice surviving for >80 days
      relative to untreated controls. CONCLUSIONS: Our results show that the Bcl-2 ASO
      and radiation combination is a highly potent therapy for nasopharyngeal cancer.
      Further examination of combination therapy with radiation and other Bcl-2 family
      targeted anticancer agents in both preclinical and clinical settings is
      definitely warranted.

PMID- 16299247
TI  - ZD6474, a novel tyrosine kinase inhibitor of vascular endothelial growth factor
      receptor and epidermal growth factor receptor, inhibits tumor growth of multiple
      nervous system tumors.
AB  - PURPOSE: Primary central nervous system (CNS) tumors represent a diverse group of
      tumor types with heterogeneous molecular mechanisms that underlie their formation
      and maintenance. CNS tumors depend on angiogenesis and often display increased
      activity of ErbB-associated pathways. Current nonspecific therapies frequently
      have poor efficacy in many of these tumor types, so there is a pressing need for
      the development of novel targeted therapies. EXPERIMENTAL DESIGN: ZD6474 is a
      novel, orally available low molecular weight inhibitor of the kinase activities
      associated with vascular endothelial growth factor receptor-2 and epidermal
      growth factor receptor. We hypothesized that ZD6474 may provide benefit in the
      treatment of several CNS tumor types. RESULTS: In mice bearing established s.c.
      tumor xenografts of CNS tumors (malignant glioma and ependymoma) or
      rhabdomyosarcoma, a limited course of ZD6474 treatment produced significant tumor
      growth delays and a high rate of partial tumor regression in most models
      examined. Mice with i.c. malignant glioma xenografts treated with ZD6474
      experienced a significant prolongation of survival. Tumors from mice treated with
      ZD6474 displayed a lower proliferative index and disrupted tumor vascularity.
      Notably, some of these models are insensitive to low molecular weight kinase
      inhibitors targeting only vascular endothelial growth factor receptor-2 or
      epidermal growth factor receptor functions, suggesting that the combined
      disruption of both epidermal growth factor receptor and vascular endothelial
      growth factor receptor-2 activities may significantly increase tumor control.
      CONCLUSIONS: In conclusion, ZD6474 shows significant activity against xenograft
      models of several primary human CNS tumor types. Consideration for clinical
      development in this disease setting seems warranted.

PMID- 16299248
TI  - Roscovitine modulates DNA repair and senescence: implications for combination
      chemotherapy.
AB  - PURPOSE: Treatment of tumor cells by chemotherapy activates a series of responses
      ranging from apoptosis to premature senescence and repair. Survival responses are
      characterized by inhibition of cyclin-dependent kinases. Because inhibition of
      cyclin-dependent kinases represents a distinctive feature of DNA damage-induced
      prosurvival responses, we investigated the possibility that the cyclin-dependent
      kinase inhibitor roscovitine modulates drug-induced responses in human
      adenocarcinoma cells, favoring cell survival. EXPERIMENTAL DESIGN: Sublethal
      concentrations of doxorubicin were used to induce premature senescence in human
      adenocarcinoma cells. The effect of the cyclin-dependent kinase inhibitor
      roscovitine on the doxorubicin-dependent cell cycle checkpoint activation and DNA
      repair pathways was evaluated. RESULTS: Roscovitine reinforces doxorubicin
      dependent G(1) checkpoint in A549 and HEC1B cells leading to decreased frequency
      of double-strand breaks and to the preferential induction of senescence and
      enhanced clonogenic survival. However, in other tumor cell lines, such as HCT116
      and H1299, combined treatment with doxorubicin and roscovitine increases the
      frequency of double-strand breaks and dramatically sensitizes to doxorubicin.
      This unexpected effect of roscovitine depends on a novel ability to inhibit DNA
      double-strand break repair processes and requires inactivation of the pRb
      pathway. CONCLUSIONS: Roscovitine, by hindering DNA repair processes, has the
      potential to inhibit recovery of mildly damaged tumor cells after doxorubicin
      treatment and to increase the susceptibility of tumor cells to chemotherapy.
      However, in some tumor cells, the cell cycle inhibitory function of roscovitine
      prevails over the DNA repair inhibitory activity, favoring premature senescence
      and clonogenic growth. These data indicate a novel mechanism underlying combined
      chemotherapy, which may have wide application in treatment of carcinomas.

PMID- 16299249
TI  - Heparin octasaccharides inhibit angiogenesis in vivo.
AB  - BACKGROUND: In previous experiments, we showed that heparin oligosaccharides
      inhibit the angiogenic cytokine fibroblast growth factor-2. Here, we present the
      first in vivo study of size-fractionated heparin oligosaccharides in four models
      of angiogenesis that are progressively less dependent on fibroblast growth factor
      2. EXPERIMENTAL DESIGN: Heparin oligosaccharides were prepared using size
      exclusion gel filtration chromatography and characterized through
      depolymerization and strong anion exchange high-performance liquid
      chromatography. Size-defined oligosaccharides (20 mg/kg/d) were given to mice
      bearing s.c. sponges that were injected with fibroblast growth factor-2 (100
      ng/d). After 14 days, octasaccharides and decasaccharides reduced the microvessel
      density to levels below control. In a second experiment, HEC-FGF2 human
      endometrial cancer cells that overexpress fibroblast growth factor-2 were
      implanted in a hollow fiber placed s.c. in vivo. Oligosaccharides were given at
      20 mg/kg/d for 2 weeks and the data again showed that octasaccharides
      significantly reduced microvessel density around the fiber (P = 0.03). In a more
      complex model, where angiogenesis was induced by a broad spectrum of growth
      factors, including vascular endothelial growth factor, we implanted H460 lung
      carcinoma cells in hollow fibers and treated the animals with oligosaccharides at
      20 mg/kg/d over 3 weeks. Octasaccharides reduced the microvessel density to that
      of control. Preliminary investigation of 6-O-desulfated heparins showed that
      these also had antiangiogenic activity. RESULTS: Finally, we examined the
      inhibitory potential of hexasaccharides and octasaccharides given at 20 mg/kg/d
      and these inhibited the growth of H460 lung carcinoma in vivo. At clinically
      attainable concentrations, significant anticoagulation (activated partial
      thromboplastin time, anti-factor Xa, and anti-factor IIa) was not observed in
      vitro unless species containing > or =16 saccharide residues were investigated.
      CONCLUSIONS: Thus, our preclinical data show that heparin octasaccharides
      represent novel antiangiogenic compounds that can be given without the
      anticoagulant effects of low molecular weight heparin.

PMID- 16299250
TI  - Intraperitoneal pretarget radioimmunotherapy with CC49 fusion protein.
AB  - PURPOSE: This study examined a pretarget radioimmunotherapy strategy for
      treatment of an i.p. tumor model (LS174T). EXPERIMENTAL DESIGN: The strategy used
      regional administration (i.p.) of a novel targeting molecule composed of four
      CC49 anti-tumor-associated glycoprotein 72 (TAG-72) single-chain antibodies
      linked to streptavidin as a fusion protein (CC49 fusion protein); 24 hours later,
      a synthetic clearing agent was administered i.v. to produce hepatic clearance of
      unbound CC49 fusion protein/synthetic clearing agent complexes. Four hours later,
      a low molecular weight radiolabeled reagent composed of biotin conjugated to the
      chelating agent 7,10-tetra-azacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)
      complexed with (111)In-, (90)Y-, or (177)Lu-DOTA-biotin was injected. RESULTS:
      Radiolocalization to tumor sites was superior with i.p. administration of
      radiolabeled DOTA-biotin as compared with i.v. administration. Imaging and
      biodistribution studies showed excellent tumor localization of radioactivity with
      (111)In- or (177)Lu-DOTA-biotin. Tumor localization of (111)In-DOTA-biotin was
      43% ID/g and 44% ID/g at 4 and 24 hours with the highest normal tissue
      localization in the kidney with 6% ID/g at 48 and 72 hours. Therapy studies with
      (90)Y-DOTA-biotin at doses of 400 to 600 microCi or (177)Lu-DOTA-biotin at doses
      of 600 to 800 microCi produced significant prolongation of survival compared with
      controls (P = 0.03 and P < 0.01). CONCLUSIONS: Pretarget radioimmunotherapy using
      regional administration of CC49 fusion protein and i.p. (90)Y- or (177)Lu-DOTA
      biotin represents a successful therapeutic strategy in the LS174T i.p. tumor
      model and this strategy may be applicable to human trials in patients with i.p.
      ovarian cancer.

PMID- 16299251
TI  - Inhibition of nuclear translocation of nuclear factor-kappaB despite lack of
      functional IkappaBalpha protein overcomes multiple defects in apoptosis signaling
      in human B-cell malignancies.
AB  - PURPOSE: Defective apoptosis signaling is a typical feature of classic Hodgkin's
      lymphoma, multiple myeloma, and activated B-cell-like diffuse large B-cell
      lymphoma. In these malignancies, the transcription factor nuclear factor-kappaB
      (NF-kappaB) is a critical mediator of apoptosis resistance and oncogenic growth,
      making it an attractive therapeutic target. Here, we sought to determine how to
      overcome apoptosis resistance experimentally in these malignancies by targeting
      NF-kappaB. EXPERIMENTAL DESIGN: We investigated the effect of different
      inhibitors of NF-kappaB on classic Hodgkin's lymphoma, multiple myeloma, and
      activated B-cell-like diffuse large B-cell lymphoma cell lines harboring
      different molecular defects in apoptosis signaling both quantitatively and
      qualitatively. RESULTS: The cyclopentenone prostaglandin, 15-deoxy-Delta12,14
      prostaglandin J(2), a known inhibitor of NF-kappaB, induced caspase-dependent
      apoptosis; it restored mitochondrial apoptotic signaling by down-regulation of X
      linked inhibitor of apoptosis protein and heat shock protein 27 and led to
      breakdown of the mitochondrial membrane potential and, finally, cleavage of
      caspase-3 irrespective of IkappaBalpha mutational status. Surprisingly, 15-deoxy
      Delta12,14-prostaglandin J(2) and the IkappaB kinase inhibitor curcumin both
      reduced nuclear levels of p65 in cell lines lacking IkappaBalpha, suggesting that
      inhibition of nuclear translocation of NF-kappaB can occur in the absence of
      IkappaBalpha. Finally, a synthetic peptide that specifically abrogates the
      assembly of the IkappaB kinase complex killed IkappaBalpha-defective cells by
      induction of apoptosis, paralleled by reduction of nuclear NF-kappaB.
      CONCLUSIONS: These results show that molecular defects in apoptotic signaling,
      such as IkappaBalpha mutations, can be circumvented by targeting NF-kappaB
      through inhibition of the IkappaB kinase complex followed by induction of
      apoptosis in classic Hodgkin's lymphoma, multiple myeloma, and activated B-cell
      like diffuse large B-cell lymphoma. Thus, targeting IkappaB kinases may represent
      an attractive therapeutic approach against these malignancies regardless of the
      mutational status of IkappaBalpha.

PMID- 16299252
TI  - Effect of the selective estrogen receptor modulator arzoxifene on repopulation of
      hormone-responsive breast cancer xenografts between courses of chemotherapy.
AB  - Selective inhibition of repopulation of clonogenic tumor cells between courses of
      chemotherapy has potential to improve the effectiveness of treatment. Here we
      study arzoxifene, a short-acting selective estrogen receptor modulator, for its
      potential to inhibit repopulation in estrogen-dependent human breast cancer MCF-7
      xenografts between courses of chemotherapy. Proliferation of tumor cells was
      evaluated by cyclin D1 expression and uptake of 5-bromo-2'-deoxyuridine.
      Arzoxifene decreased cell proliferation in xenografts. To model adjuvant
      treatment of human breast cancer, MCF-7 cells were injected s.c. into nude mice
      and four groups of mice received the following treatments beginning after
      implantation: (a) control (vehicle solution); (b) arzoxifene alone, 5 days per
      week by oral gavage for 3 weeks; (c) 5-fluorouracil (5-FU) or paclitaxel i.p.
      weekly, for 3 doses; and (d) arzoxifene following each cycle of chemotherapy. The
      incidence of tumors with volume > or =50 mm(3) was determined as a function of
      time. MCF-7 xenografts developed in 100% of control mice by 4 weeks after
      implantation. Paclitaxel or 5-FU alone had minor effects to delay the appearance
      of xenografts whereas arzoxifene alone caused longer delay. Combined treatment
      with arzoxifene given between cycles of 5-FU or paclitaxel had substantial
      effects, with approximately 50% tumor incidence by 5 weeks. Our results indicate
      that arzoxifene can inhibit repopulation of hormone-responsive MCF-7 breast
      cancer xenografts when given between courses of chemotherapy. The scheduling of
      short-acting hormonal agents between courses of adjuvant chemotherapy for human
      breast cancer has potential to improve the outcome of treatment.

PMID- 16299253
TI  - Carbonic anhydrase II is a tumor vessel endothelium-associated antigen targeted
      by dendritic cell therapy.
AB  - Tumor-associated antigens are promising candidates as target molecules for
      immunotherapy and a wide variety of tumor-associated antigens have been
      discovered through the presence of serum antibodies in cancer patients. We
      previously conducted dendritic cell therapy on 10 malignant melanoma patients and
      shrinkage or disappearance of metastatic tumors with massive necrosis occurred in
      two patients. In this study, we found a 29-kDa protein against which antibody was
      elicited by dendritic cell therapy in one of the two patients. Matrix-assisted
      laser desorption ionization-time of flight/mass spectrometry analysis of the
      protein isolated by two-dimensional electrophoresis combined with Western blots
      revealed that the 29-kDa protein was carbonic anhydrase II (CA-II).
      Immunohistochemistry of the tumors and normal tissues showed that CA-II was
      expressed in the tumor vessel but not in normal vessel endothelium. CA-II
      expression in tumor endothelium was observed as well in other cancers including
      esophageal, renal, and lung cancers. In an in vitro angiogenesis model, CA-II
      expression of normal human vein endothelial cells was significantly up-regulated
      when cells were cultured in the acidic and hypoxic conditions indicative of a
      tumor environment. These findings suggest that CA-II is a tumor vessel
      endothelium-associated antigen in melanoma and other cancers, and elicitation of
      serum anti-CA-II antibody by dendritic cell therapy may be associated with good
      clinical outcome including tumor reduction.

PMID- 16299254
TI  - Phosphatidylinositol 3-kinase mediates angiogenesis and vascular permeability
      associated with ovarian carcinoma.
AB  - PURPOSE: To assess the role of phosphatidylinositol-3 kinase (PI3K) inhibition in
      vascular permeability, angiogenesis, and vascular remodeling in tumor vessels and
      peritoneal lining in an athymic mouse model of i.p. human ovarian carcinoma.
      EXPERIMENTAL DESIGN: Mice were inoculated i.p. with cells from the human ovarian
      cancer cell line, OVCAR-3. Fourteen days after inoculation, mice were treated
      with or without the PI3K inhibitor LY294002, 3 days weekly for 4 weeks. At the
      end of the experiment, some mice were anesthetized and injected via the tail vein
      with FITC-labeled lycopersicon lectin and perfused through the aorta before
      sacrifice. The peritoneal wall and tumor from all mice were removed and embedded
      in 10% agarose. Tumor sections were visualized by fluorescence microscopy.
      RESULTS: Ascites in the LY294002-treated group (0.69 +/- 0.27 mL) was reduced by
      72.4% compared with the control group (2.5 +/- 1.2 mL). Tumor burden in the
      LY294002-treated group (0.62 +/- 0.32 g) was reduced by 47.3% compared with the
      control group (1.18 +/- 0.41 g). LY294002 inhibited peritoneal and tumor
      vascularization resulting in numerous leaky, irregular, tortuous vessels in
      scant, straight, relatively impermeable vessels. CONCLUSIONS: The data indicate
      that LY294002 inhibits ascites formation in our mouse model of human ovarian
      cancer by inhibiting tumor and peritoneal neovascularization as well as vascular
      permeability. The data also show that LY294002 directly inhibits vascular
      endothelial growth factor (VEGF) protein expression and release from ovarian
      carcinoma and suggest that LY294002 blocks the VEGF signaling pathway involved in
      angiogenesis and vascular permeability.

PMID- 16299256
TI  - The estrogen receptors alpha, beta, and beta cx.

PMID- 16299257
TI  - Noninvasive Doppler-derived myocardial performance index in rats with myocardial
      infarction: validation and correlation by conductance catheter.
AB  - The rodent model of myocardial infarction (MI) is extensively used in heart
      failure studies. However, long-term follow-up of echocardiographic left
      ventricular (LV) function parameters such as the myocardial performance index
      (MPI) and its ratio with the fractional shortening (LVFS/MPI) has not been
      validated in conjunction with invasive indexes, such as those derived from the
      conductance catheter (CC). Sprague-Dawley rats with left anterior descending
      coronary artery ligation (MI group, n = 9) were compared with a sham-operated
      control group (n = 10) without MI. Transthoracic echocardiography (TTE) was
      performed every 2 wk over an 8-wk period, after which classic TTE parameters,
      especially MPI and LVFS/MPI, were compared with invasive indexes obtained by
      using a CC. Serial TTE data showed significant alterations in the majority of the
      noninvasive functional and structural parameters (classic and novel) studied in
      the presence of MI. Both MPI and LVFS/MPI significantly (P < 0.05 for all
      reported values) correlated with body weight (r = -0.58 and 0.76 for MPI and
      LVFS/MPI, respectively), preload recruitable stroke work (r = -0.61 and 0.63), LV
      end-diastolic pressure (LVEDP) (r = 0.82 and -0.80), end-diastolic volume (r =
      0.61 and -0.58), and end-systolic volume (r = 0.46 and -0.48). Forward stepwise
      linear regression analysis revealed that, of all variables tested, LVEDP was the
      only independent determinant of MPI (r = 0.84) and LVFS/MPI (r = 0.83). We
      conclude that MPI and LVFS/MPI correlate strongly and better than the classic
      noninvasive TTE parameters with established, invasively assessed indexes of
      contractility, preload, and volumetry. These findings support the use of these
      two new noninvasive indexes for long-term analysis of the post-MI LV remodeling.

PMID- 16299255
TI  - In vitro and in vivo effects and mechanisms of celecoxib-induced growth
      inhibition of human hepatocellular carcinoma cells.
AB  - PURPOSE: Cyclooxygenase-2 (COX-2) inhibitors cause growth inhibition of human
      hepatocellular carcinoma cells but it remains unclear whether this is both COX-2
      dependent and independent. The related mechanisms remain to be determined. The
      present study was aimed to determine the effect of celecoxib on growth of
      hepatocellular carcinoma cells and xenografts and the related mechanisms.
      EXPERIMENTAL DESIGN: Both low COX-2 expressing PLC/PRF/5 and high COX-2
      expressing HuH7 cells, and nude mice bearing hepatocellular carcinoma xenografts
      were used to study the effect and mechanisms of celecoxib on hepatocellular
      carcinoma cell growth. RESULTS: Celecoxib resulted in a comparable growth
      inhibition of both hepatocellular carcinoma cells that was associated with
      decreased production of prostaglandin E(2) and increased peroxisome proliferator
      activated receptor gamma in both cells. Addition of prostaglandin E(2) only
      partially counteracted the effect of celecoxib on both cells. Celecoxib resulted
      in a significant reduction of retinoblastoma phosphorylation and DP1/E2F1 complex
      in both cells. Celecoxib caused a significant increase of apoptosis and
      activation of caspase-3 and caspase-9 in both cells. In nude mice inoculated with
      HuH7 cells, celecoxib resulted in decreased frequency and mean weight of
      hepatocellular carcinoma xenografts. CONCLUSION: The present study showed that
      celecoxib causes COX-2-dependent and COX-2-independent growth inhibition of
      hepatocellular carcinoma cells and xenografts by (a) decreased retinoblastoma
      phosphorylation and DP1/E2F1 complex; (b) increased activation of caspase-3 and
      caspase-9; and (c) increased expression of proliferator-activated receptor gamma.
      The present study significantly extended our knowledge on the effect and
      mechanisms of celecoxib-induced inhibition of hepatocellular carcinoma cell
      growth.

PMID- 16299258
TI  - Nonuniformity of axial and circumferential remodeling of large coronary veins in
      response to ligation.
AB  - The pressure-induced remodeling of coronary veins is important in coronary venous
      retroperfusion. Our hypothesis is that the response of the large coronary veins
      to pressure overload will depend on the degree of myocardial support. Eleven
      normal Yorkshire swine from either sex, weighing 31-39 kg, were studied. Five
      pigs underwent ligation of the left anterior descending (LAD) vein, and six
      served as sham-operated controls. The ligation of the coronary vein caused an
      increase in pressure intermediate to arterial and venous values. After 2 wk of
      ligation, the animals were euthanized and the coronary vessels were perfusion
      fixed with glutaraldehyde. The LAD vein was sectioned, and detailed morphometric
      measurements were made along its length from the point of ligation near the base
      down to the apex of the heart. The structural remodeling of the vein was
      circumferentially nonuniform because the vein is partially embedded in the
      myocardium; it was also axially nonuniform because it is tethered to the
      myocardium to different degrees along its axial length. The wall area was
      significantly larger in the experimental group, whereas luminal area in the
      proximal LAD vein was significantly smaller in the same group compared with sham
      operated controls. The wall thickness-to-radius ratio was also significantly
      larger in the experimental group in proportion to the increase in pressure. The
      major conclusion of this study is that the response of the vein depends on the
      local wall stress, which is, in part, determined by the surrounding tissue.
      Furthermore, the geometric remodeling of the coronary vein restores the
      circumferential stress to the homeostatic value.

PMID- 16299259
TI  - Stem cell mobilization by hyperbaric oxygen.
AB  - We hypothesized that exposure to hyperbaric oxygen (HBO(2)) would mobilize
      stem/progenitor cells from the bone marrow by a nitric oxide (*NO) -dependent
      mechanism. The population of CD34(+) cells in the peripheral circulation of
      humans doubled in response to a single exposure to 2.0 atmospheres absolute (ATA)
      O(2) for 2 h. Over a course of 20 treatments, circulating CD34(+) cells increased
      eightfold, although the overall circulating white cell count was not
      significantly increased. The number of colony-forming cells (CFCs) increased from
      16 +/- 2 to 26 +/- 3 CFCs/100,000 monocytes plated. Elevations in CFCs were
      entirely due to the CD34(+) subpopulation, but increased cell growth only
      occurred in samples obtained immediately posttreatment. A high proportion of
      progeny cells express receptors for vascular endothelial growth factor-2 and for
      stromal-derived growth factor. In mice, HBO(2) increased circulating stem cell
      factor by 50%, increased the number of circulating cells expressing stem cell
      antigen-1 and CD34 by 3.4-fold, and doubled the number of CFCs. Bone marrow *NO
      concentration increased by 1,008 +/- 255 nM in association with HBO(2). Stem cell
      mobilization did not occur in knockout mice lacking genes for endothelial *NO
      synthase. Moreover, pretreatment of wild-type mice with a *NO synthase inhibitor
      prevented the HBO(2)-induced elevation in stem cell factor and circulating stem
      cells. We conclude that HBO(2) mobilizes stem/progenitor cells by stimulating *NO
      synthesis.

PMID- 16299260
TI  - Isolation and characterization of coronary endothelial and smooth muscle cells
      from A1 adenosine receptor-knockout mice.
AB  - Mice have been used widely in in vivo and in vitro cardiovascular research. The
      availability of knockout mice provides further clues to the physiological
      significance of specific receptor subtypes. Adenosine A(1) receptor (A(1)AR)
      knockout (A(1)KO) mice and their wild-type (A(1)WT) controls were employed in
      this investigation. The heart and aortic arch were carefully removed and
      retroinfused with enzyme solution (1 mg/ml collagenase type I, 0.5 mg/ml soybean
      trypsin inhibitor, 3% BSA, and 2% antibiotics) through the aortic arch. The
      efflux was collected at 30-, 60-, and 90-min intervals. The cells were
      centrifuged, and the pellets were mixed with medium [medium 199-F-12 medium with
      10% FBS and 2% antibiotics (for endothelial cells) and advanced DMEM with 10%
      FBS, 10% mouse serum, 2% GlutaMax, and 2% antibiotics (for smooth muscle cells)]
      and plated. Endothelial cells were characterized by a cobblestone appearance and
      positive staining with acetylated LDL labeled with 1,1'-dioctadecyl-3,3,3',3
      tetramethylindocarbocyanine perchlorate. Smooth muscle cells were characterized
      by positive staining of smooth muscle alpha-actin and smooth muscle myosin heavy
      chain. Homogeneity of the smooth muscle cells was approximately 91%. Western blot
      analysis showed expression of smoothelin in the cells from passages 3, 7, and 11
      in A(1)WT and A(1)KO mice. Furthermore, the A(1)AR was characterized by Western
      blot analysis using an A(1)AR-specific antibody. To our knowledge, this is the
      first isolation and successful characterization of smooth muscle cells from the
      mouse coronary system.

PMID- 16299262
TI  - Effect of modulating cardiac A1 adenosine receptor expression on protection with
      ischemic preconditioning.
AB  - Activation of A(1) adenosine receptors (A(1)ARs) may be a crucial step in
      protection against myocardial ischemia-reperfusion (I/R) injury; however, the use
      of pharmacological A(1)AR antagonists to inhibit myocardial protection has
      yielded inconclusive results. In the current study, we have used mice with
      genetically modified A(1)AR expression to define the role of A(1)AR in intrinsic
      protection and ischemic preconditioning (IPC) against I/R injury. Normal wild
      type (WT) mice, knockout mice with deleted (A(1)KO(-/-)) or single-copy
      (A(1)KO(+/-)) A(1)AR, and transgenic mice (A(1)TG) with increased cardiac A(1)AR
      expression underwent 45 min of left anterior descending coronary artery
      occlusion, followed by 60 min of reperfusion. Subsets of each group were
      preconditioned with short durations of ischemia (3 cycles of 5 min of occlusion
      and 5 min of reperfusion) before index ischemia. Infarct size (IF) in WT,
      A(1)KO(+/-), and A(1)KO(-/-) mice was (in % of risk region) 58 +/- 3, 60 +/- 4,
      and 61 +/- 2, respectively, and was less in A(1)TG mice (39 +/- 4, P < 0.05). A
      strong correlation was observed between A(1)AR expression level and response to
      IPC. IF was significantly reduced by IPC in WT mice (35 +/- 3, P < 0.05 vs. WT),
      A(1)KO(+/-) + IPC (48 +/- 4, P < 0.05 vs. A(1)KO(+/-)), and A(1)TG + IPC mice (24
      +/- 2, P < 0.05 vs. A(1)TG). However, IPC did not decrease IF in A(1)KO(-/-) +
      IPC mice (63 +/- 2). In addition, A(1)KO(-/-) hearts subjected to global I/R
      injury demonstrated diminished recovery of developed pressure and diastolic
      function compared with WT controls. These findings demonstrate that A(1)ARs are
      critical for protection from myocardial I/R injury and that cardioprotection with
      IPC is relative to the level of A(1)AR gene expression.

PMID- 16299261
TI  - Hypertonic saline dextran after burn injury decreases inflammatory cytokine
      responses to subsequent pneumonia-related sepsis.
AB  - The present study examined the hypothesis that hypertonic saline dextran (HSD),
      given after an initial insult, attenuates exaggerated inflammation that occurs
      with a second insult. Adult rats (n = 15 per group) were divided into groups 1
      (sham burn), 2 [40% total body surface area burn + 4 ml/kg isotonic saline (IS) +
      4 ml.kg(-1).% burn(-1) lactated Ringer solution (LR)], and 3 (burn + 4 ml/kg HSD
      + LR), all studied 24 h after burns. Groups 4 (sham burn), 5 (burn + IS + LR),
      and 6 (burns + HSD + LR) received intratracheal (IT) vehicle 7 days after burns;
      groups 7 (burn + IS + LR) and 8 (burn + HSD + LR) received IT Streptococcus
      pneumoniae (4 x 10(6) colony-forming units) 7 days after burn. Groups 4-8 were
      studied 8 days after burn and 24 h after IT septic challenge. When compared with
      sham burn, contractile defects occurred 24 h after burn in IS-treated but not HSD
      treated burns. Cardiac inflammatory responses (pg/ml TNF-alpha) were evident with
      IS (170 +/- 10) but not HSD (45 +/- 5) treatment vs. sham treatment (80 +/- 15).
      Pneumonia-related sepsis 8 days after IS-treated burns (group 7) exacerbated TNF
      alpha responses/contractile dysfunction vs. IS-treated burns in the absence of
      sepsis (P < 0.05). Sepsis that occurred after HSD-treated burns (group 8) had
      less myocyte TNF-alpha secretion/better contractile function than IS-treated
      burns given septic challenge (group 7, P < 0.05). We conclude that an initial
      burn injury exacerbates myocardial inflammation/dysfunction occurring with a
      second insult; giving HSD after the initial insult attenuates myocardial
      inflammation/dysfunction associated with a second hit, suggesting that HSD
      reduces postinjury risk for infectious complications.

PMID- 16299263
TI  - Cortical spreading depression confounds concentration-dependent pial arteriolar
      dilation during N-methyl-D-aspartate superfusion.
AB  - Pial arterioles do not express N-methyl-D-aspartate (NMDA) receptors but dilate
      in response to topical NMDA application. We explored the mechanism underlying
      NMDA-mediated responses in murine pial arterioles (11-31 microm), using a closed
      cranial window preparation, and found that arteriolar dilation was not
      concentration dependent. Pial arteriolar diameter abruptly increased within 3 min
      of superfusing 50 or 100 microM NMDA. Dilation reached a peak within 1 min (46 +/
      14%) and then declined to a plateau (28 +/- 13%) for the duration of
      superfusion. Whereas a higher concentration (200 microM) did not produce further
      dilation, lower concentrations (1-10 microM) did not dilate the arterioles at
      all. MK-801 (10 microM) abrogated the dilation response, whereas Nomega-nitro-L
      arginine (1 mM) attenuated the peak and abolished the sustained dilation during
      NMDA superfusion. We determined that NMDA-induced pial arteriolar responses were
      evoked by cortical spreading depression, because abrupt vasodilation during 50 or
      100 microM NMDA superfusion was associated with a large negative slow potential
      shift and electrocorticogram suppression that spread from the superfusion window
      to distant cortical areas. Our data suggest that the responses of pial arterioles
      to NMDA are caused in part by neurovascular coupling due to cortical spreading
      depression.

PMID- 16299264
TI  - Extracellular lactate as a dynamic vasoactive signal in the rat retinal
      microvasculature.
AB  - We tested the hypothesis that extracellular lactate regulates the function of
      pericyte-containing retinal microvessels. Although abluminally positioned
      pericytes appear to adjust capillary perfusion by contracting and relaxing,
      knowledge of the molecular signals that regulate the contractility of these mural
      cells is limited. Here, we focused on lactate because this metabolic product is
      in the retinal extracellular space under both physiological and
      pathophysiological conditions. In microvessels freshly isolated from the adult
      rat retina, we used perforated-patch pipettes to monitor ionic currents, fura-2
      to measure calcium levels, and time-lapse photography to visualize changes in
      mural cell contractility and lumen diameter. During lactate exposure, pericyte
      calcium rose; these cells contracted, and lumens constricted. This contractile
      response appears to involve a cascade of events resulting in the inhibition of
      Na+/Ca2+ exchangers (NCXs), the decreased of which function causes pericyte
      calcium to increase and contraction to be triggered. On the basis of our
      observation that gap junction uncouplers minimized the lactate-induced rise in
      pericyte calcium, we propose that the NCXs inhibited by lactate are predominately
      located in the endothelium. Indicative of the importance of endothelial/pericyte
      gap junctions, uncouplers of these junctions switched the pericyte response to
      lactate from contraction to relaxation. In addition, we observed that hypoxia,
      which closes microvascular gap junctions, also switched lactate's effect from
      vasocontraction to vasorelaxation. Thus the response of pericyte-containing
      retinal microvessels to extracellular lactate is metabolically modulated. The
      ability of lactate to serve as a vasoconstrictor when energy supplies are ample
      and a vasodilator under hypoxic conditions may be an efficient mechanism to link
      capillary function with local metabolic need.

PMID- 16299265
TI  - Mitogen-activated protein kinase activation and regulation in the pressure-loaded
      fetal ovine heart.
AB  - The mitogen-activated protein (MAP) kinase signaling pathways help to mediate the
      hypertrophic response of the pressure-loaded adult heart, although their
      importance in fetal myocardium is less known. The goal of this study was to
      determine the role the MAP kinase signaling pathways play in regulating the
      response of the fetal heart to a pressure load. Aortic (Ao) and pulmonary artery
      (PA) bands were placed in 132-day fetal sheep for 7 days. Protein levels of the
      total and active (phosphorylated) terminal MAP kinases extracellular signal
      regulated kinase (ERK/P-ERK), c-Jun NH(2)-terminal kinase (JNK/P-JNK), and p38/P
      p38 and the MAP kinase phosphatases MKP-1, MKP-2, and MKP-3 were made in the
      right and left ventricular (RV and LV) free walls. In both Ao- and PA-banded
      animals, total heart weight normalized to body weight was significantly
      increased, largely due to an increase in RV free wall mass in the Ao-banded
      animals and an increase in septal mass in the PA-banded fetuses. Total protein
      levels of the three terminal kinases and of P-ERK and P-JNK remained stable in
      both groups of banded animals. However, P-p38 was significantly increased in RV
      and LV of Ao- and PA-banded fetuses. Whereas MKP-1 and MKP-2 protein levels were
      unchanged following Ao- and PA-banding, MKP-3 protein levels were significantly
      increased in the RV of the PA-banded animals. These findings indicate that the
      MAP kinase signaling pathways are active in the fetal heart and help to modulate
      the response of prenatal myocardium to a pressure load.

PMID- 16299266
TI  - Myocardial fibrosis, impaired coronary hemodynamics, and biventricular
      dysfunction in salt-loaded SHR.
AB  - Arterial pressure in most experimental and clinical hypertensions is exacerbated
      by salt. The effects of salt excess on right and left ventricular (RV and LV,
      respectively) functions and their respective coronary vasodilatory responses have
      been less explored. We therefore examined the effects of 8 wk of NaCl excess (8%
      in food) on arterial pressure, RV and LV functions (maximal rate of increase and
      decrease of ventricular pressure; dP/dt(max) and dP/dt(min)), coronary
      hemodynamics (microspheres), and collagen content (hydroxyproline assay and
      collagen volume fraction) in young adult normotensive Wistar-Kyoto (WKY) and
      spontaneously hypertensive rats (SHR), aged 16 wk by the end of the study.
      Prolonged salt excess in WKY and SHR elevated pressure only modestly, but it
      markedly increased LV mass, especially in SHR. Moreover, salt excess
      significantly impaired RV and LV diastolic function in SHR but only LV diastolic
      function in WKY rats. However, salt loading affected neither RV nor LV
      contractile function in both strains. Interstitial and perivascular collagen
      deposition was increased, whereas coronary vasodilatory responses to dipyridamole
      diminished in both ventricles in the salt-loaded SHR but not in WKY rats.
      Therefore, accumulation of ventricular collagen as well as altered myocardial
      perfusion importantly contributed to the development of salt-related RV and LV
      dysfunctions in this model of naturally occurring hypertension. The unique
      effects of salt loading on both ventricles in SHR, but not WKY rats, strongly
      suggest that nonhemodynamic mechanisms in hypertensive disease participate
      pathophysiologically with salt-loading hypertension. These findings point to the
      conclusion that the concept of "salt sensitivity" in hypertension is far more
      complex than simply its effects on arterial pressure or the LV.

PMID- 16299267
TI  - Inhaled nitric oxide does not reduce systemic vascular resistance in mice.
AB  - Inhaled nitric oxide (NO) is a highly selective pulmonary vasodilator. It was
      recently reported that inhaled NO causes peripheral vasodilatation after
      treatment with a NO synthase (NOS) inhibitor. These findings suggested the
      possibility that inhibition of endogenous NOS uncovered the systemic vasodilating
      effect of NO or NO adducts absorbed via the lungs during NO inhalation. To learn
      whether inhaled NO reduces systemic vascular resistance in the absence of
      endothelial NOS, we studied the systemic vascular effects of NO breathing in wild
      type mice treated without and with the NOS inhibitor N(omega)-nitro-l-arginine
      methyl ester and in NOS3-deficient (NOS3(-/-)) mice. During general anesthesia,
      the cardiac output, left ventricular function, and systemic vascular resistance
      were not altered by NO breathing at 80 parts/million in both genotypes. Breathing
      NO in air did not alter blood pressure and heart rate, as measured by tail-cuff
      and telemetric methods, in either awake wild-type mice (whether or not they were
      treated with N(omega)-nitro-l-arginine methyl ester), or in awake NOS3(-/-) mice.
      Our findings suggest that absorption of NO or adducts during NO breathing is
      insufficient to cause systemic vasodilation in mice, even when endogenous
      endothelial NO production is congenitally absent.

PMID- 16299268
TI  - Membrane cholesterol: a crucial molecule affecting interactions of microbial
      pathogens with mammalian cells.

PMID- 16299270
TI  - Haemophilus ducreyi targets Src family protein tyrosine kinases to inhibit
      phagocytic signaling.
AB  - Haemophilus ducreyi, the etiologic agent of the sexually transmitted disease
      chancroid, has been shown to inhibit phagocytosis of both itself and secondary
      targets in vitro. Immunodepletion of LspA proteins from H. ducreyi culture
      supernatant fluid abolished this inhibitory effect, indicating that the LspA
      proteins are necessary for the inhibition of phagocytosis by H. ducreyi.
      Fluorescence microscopy revealed that macrophages incubated with wild-type H.
      ducreyi, but not with a lspA1 lspA2 mutant, were unable to complete development
      of the phagocytic cup around immunoglobulin G-opsonized targets. Examination of
      the phosphotyrosine protein profiles of these two sets of macrophages showed that
      those incubated with wild-type H. ducreyi had greatly reduced phosphorylation
      levels of proteins in the 50-to-60-kDa range. Subsequent experiments revealed
      reductions in the catalytic activities of both Lyn and Hck, two members of the
      Src family of protein tyrosine kinases that are known to be involved in the
      proximal signaling steps of Fcgamma receptor-mediated phagocytosis. Additional
      experiments confirmed reductions in the levels of both active Lyn and active Hck
      in three different immune cell lines, but not in HeLa cells, exposed to wild-type
      H. ducreyi. This is the first example of a bacterial pathogen that suppresses Src
      family protein tyrosine kinase activity to subvert phagocytic signaling in
      hostcells.

PMID- 16299269
TI  - Insight into a conserved lifestyle: protein-carbohydrate adhesion strategies of
      vector-borne pathogens.

PMID- 16299272
TI  - beta-Arrestin 1 participates in platelet-activating factor receptor-mediated
      endocytosis of Streptococcus pneumoniae.
AB  - Pneumococci traverse eukaryotic cells within vacuoles without intracytoplasmic
      multiplication. The platelet-activating factor receptor (PAFr) has been suggested
      as a portal of entry. Pneumococci colocalized with PAFr on endothelial cells and
      PAFr-/- mice showed a substantially impaired ability to support bacterial
      translocation, particularly from blood to brain. Pneumococci-induced
      colocalization of PAFr and beta-arrestin 1 at the plasma membrane of endothelial
      cells and PAFr-mediated pneumococcal uptake in transfected COS cells were greatly
      increased by cotransfection with the scaffold/adapter protein beta-arrestin 1.
      Activation of extracellular signal-regulated kinase kinases was required for
      uptake and was limited to the cytoplasmic compartment, consistent with activation
      by beta-arrestin rather than PAFr. Uptake of the pneumococcal vacuole involved
      clathrin, and half the bacteria proceeded into vacuoles marked by Rab5 and later
      Rab7, the classical route to the lysosome. Overexpression of beta-arrestin in
      endothelial cells decreased colocalization with Rab7. We conclude that the
      association of beta-arrestin with the PAFr contributes to successful
      translocation of pneumococci.

PMID- 16299271
TI  - Host restriction of Salmonella enterica serotype Typhi is not caused by
      functional alteration of SipA, SopB, or SopD.
AB  - Salmonella enterica serotype Typhi is a strictly human adapted pathogen that does
      not cause disease in nonprimate vertebrate hosts, while Salmonella enterica
      serotype Typhimurium is a broad-host-range pathogen. Serotype Typhi lacks some of
      the proteins (effectors) exported by the invasion-associated type III secretion
      system that are required by serotype Typhimurium for eliciting fluid secretion
      and inflammation in bovine ligated ileal loops. We investigated whether the
      remaining serotype Typhi effectors implicated in enteropathogenicity (SipA, SopB,
      and SopD) are functionally exchangeable with their serotype Typhimurium
      homologues. Serotype Typhi elicited fluid accumulation in bovine ligated ileal
      loops at levels similar to those elicited by a noninvasive serotype Typhimurium
      strain (the sipA sopABDE2 mutant) or by sterile culture medium. However,
      introduction of the cloned serotype Typhi sipA, sopB, and sopD genes complemented
      the ability of a serotype Typhimurium sipA sopABDE2 mutant to elicit fluid
      secretion in bovine ligated ileal loops. Introduction of the cloned serotype
      Typhi sipA, sopB, and sopD genes increased the invasiveness of a serotype
      Typhimurium sipA sopABDE2 mutant for human colon carcinoma epithelial (HT-29 and
      T84) cells and bovine kidney (MDBK) cells. Translational fusions between the
      mature TEM-1 beta-lactamase reporter and SipA or SopD demonstrated that serotype
      Typhi translocates these effectors into host cells. We conclude that the
      inability of serotype Typhi to cause fluid accumulation in bovine ligated ileal
      loops is not caused by a functional alteration of its SipA, SopB, and SopD
      effector proteins with respect to their serotype Typhimurium homologues.

PMID- 16299273
TI  - Reduction of astrogliosis by early treatment of pneumococcal meningitis measured
      by simultaneous imaging, in vivo, of the pathogen and host response.
AB  - We developed a method for simultaneous in vivo biophotonic monitoring of
      pneumococcal meningitis and the accompanying neuronal injury in live transgenic
      mice. Streptococcus pneumoniae engineered for bioluminescence (lux) was used for
      direct visualization of disease progression and antibiotic treatment in a mouse
      model of meningitis. The host response was monitored in transgenic mice
      containing an inducible firefly luciferase (luc) reporter gene under
      transcriptional control of the mouse glial fibrillary acidic protein (GFAP)
      promoter. Based on the different spectra of light emission and substrate
      requirements for lux and luc, we were able to separately monitor the two
      reporters using a highly sensitive in vivo imaging system. The level of neuronal
      damage and recovery following antibiotic treatment was dependent on the time of
      treatment. This model has potential for simultaneous multiparameter monitoring
      and testing of therapies that target the pathogen or host response to prevent
      neuronal injury and recovery.

PMID- 16299274
TI  - Helicobacter pylori activates myosin light-chain kinase to disrupt claudin-4 and
      claudin-5 and increase epithelial permeability.
AB  - Helicobacter pylori is a spiral, gram-negative bacterium that specifically and
      persistently infects the human stomach. In some individuals, H. pylori-induced
      chronic gastritis may progress to gastroduodenal ulcers and gastric cancer.
      Currently, the host-microbe interactions that determine the clinical outcome of
      infection are not well defined. H. pylori strains capable of disrupting the
      gastric epithelial barrier may increase the likelihood of developing serious
      disease. In this study, H. pylori strain SS1 increased gastric, but not small
      intestinal, permeability in C57BL/6 mice. H. pylori strain SS1 was able to
      directly increase paracellular permeability, in the absence of host inflammatory
      cells, by disrupting the tight-junctional proteins occludin, claudin-4, and
      claudin-5 in confluent nontransformed epithelial cells. H. pylori SS1 also
      reduced claudin-4 protein levels in human gastric AGS cells. The ability of H.
      pylori SS1 to increase permeability appeared to be independent of the well
      characterized virulence factors vacuolating cytotoxin and CagA protein. H. pylori
      activated myosin light-chain kinase in epithelial cells to phosphorylate myosin
      light chain and increase permeability by disrupting claudin-4 and claudin-5. The
      bacterial factor responsible for increasing epithelial permeability was heat
      sensitive, membrane bound, and required apical contact with monolayers. In
      conclusion, disruptions of the tight junctions observed in this study implicate
      host cell signaling pathways, including the phosphorylation of myosin light chain
      and the regulation of tight-junctional proteins claudin-4 and claudin-5, in the
      pathogenesis of H. pylori infection.

PMID- 16299275
TI  - Decreased in situ expression of interleukin-10 receptor is correlated with the
      exacerbated inflammatory and cytotoxic responses observed in mucosal
      leishmaniasis.
AB  - Human infection with Leishmania braziliensis can lead to cutaneous leishmaniasis
      (CL) or mucosal leishmaniasis (ML). We hypothesize that the intense tissue
      destruction observed in ML is a consequence of an uncontrolled exacerbated
      inflammatory immune response, with cytotoxic activity. For the first time, this
      work identifies the cellular sources of inflammatory and antiinflammatory
      cytokines, the expression of effector molecules, and the expression of
      interleukin-10 (IL-10) receptor in ML and CL lesions by using confocal
      microscopy. ML lesions displayed a higher number of gamma interferon (IFN-gamma)
      producing cells than did CL lesions. In both ML and CL, CD4+ cells represented
      the majority of IFN-gamma-producing cells, followed by CD8+ cells and CD4- CD8-
      cells. The numbers of tumor necrosis factor alpha-positive cells, as well as
      those of IL-10-producing cells, were similar in ML and CL lesions. The effector
      molecule granzyme A showed greater expression in ML than in CL lesions, while
      inducible nitric oxide synthase did not. Finally, the expression of IL-10
      receptor was lower in ML than in CL lesions. Thus, our data identified distinct
      cytokine and cell population profiles for CL versus ML patients and provide a
      possible mechanism for the development of ML disease through the demonstration
      that low expression of IL-10 receptor is present in conjunction with a cytotoxic
      and inflammatory profile in ML.

PMID- 16299276
TI  - Structure, cellular distribution, antigenicity, and biological functions of
      Fonsecaea pedrosoi ceramide monohexosides.
AB  - Monohexosylceramides (CMHs, or cerebrosides) have been reported as membrane and
      cell wall constituents of both pathogenic and nonpathogenic fungi, presenting
      remarkable differences in their ceramide moiety compared to mammalian CMHs.
      Current evidence suggests that CMHs are involved in fungal differentiation and
      growth and contribute to host immune response. Here we describe a structural
      diversity between cerebrosides obtained from different forms of the human
      pathogen Fonsecaea pedrosoi. The major CMH species produced by conidial forms
      displayed the same structure previously demonstrated by our group for mycelia, an
      N-2'-hydroxyhexadecanoyl-1-beta-d-glucopyranosyl-9-methyl-4,8-sphingadienine.
      However, the major cerebroside species purified from sclerotic cells carries an
      additional hydroxyl group, bound to its long-chain base. The structural
      difference between cerebrosides from mycelial and sclerotic cells was apparently
      not relevant for their antigenicity, since they were both recognized at similar
      levels by sera from individuals with chromoblastomycosis and a monoclonal
      antibody to a conserved cerebroside structure. Preincubation of fungal cells with
      anti-CMH monoclonal antibodies had no effect on the interaction of F. pedrosoi
      sclerotic cells with murine macrophages. In contrast to what has been described
      for other fungal species, sclerotic bodies are resistant to the antifungal action
      of anti-CMH antibodies. Immunofluorescence analysis showed that recognition of
      sclerotic cells by these antibodies only occurs at cell wall regions in which
      melanization is not evident. Accordingly, melanin removal with alkali results in
      an increased reaction of fungal cells with anti-CMH antibodies. Our results
      indicate that cerebroside expression in F. pedrosoi cells is associated with
      dimorphism and melanin assembly on the fungal cell wall.

PMID- 16299277
TI  - Demonstration of OspC type diversity in invasive human lyme disease isolates and
      identification of previously uncharacterized epitopes that define the specificity
      of the OspC murine antibody response.
AB  - Outer surface protein C (OspC) of the Lyme disease spirochetes is an important
      virulence factor that has potential utility for vaccine development. Of the 21
      OspC types that have been identified, it has been postulated that types A, B, I,
      and K are specifically associated with invasive infections. Through an analysis
      of isolates collected from patients in Maryland we found that OspC types C, D,
      and N are also associated with invasive infections. This observation suggests
      that there is greater diversity in the group of OspC types associated with
      invasive infection than has been previously suggested. Detailed knowledge of the
      antigenic structure of OspC is essential for vaccine development. To determine if
      the antibody response to OspC is type specific, recombinant proteins of several
      different OspC types were immunoblotted and screened with sera from mice infected
      with isolates having known OspC types. These analyses revealed a high degree of
      specificity in the antibody response and suggested that the immunodominant
      epitopes of OspC reside in the variable domains of the protein. To localize these
      epitopes, OspC fragments were generated and screened with serum collected from
      infected mice. These analyses led to identification of previously uncharacterized
      epitopes that define the type specificity of the OspC antibody response. These
      analyses provide important insight into the antigenic structure of OspC and also
      provide a basis for understanding the variable nature of the antibody response to
      this important virulence factor of the Lyme disease spirochetes.

PMID- 16299278
TI  - Active and passive intranasal immunizations with streptococcal surface protein
      C5a peptidase prevent infection of murine nasal mucosa-associated lymphoid
      tissue, a functional homologue of human tonsils.
AB  - C5a peptidase, also called SCPA (surface-bound C5a peptidase), is a surface-bound
      protein on group A streptococci (GAS), etiologic agents for a variety of human
      diseases including pharyngitis, impetigo, toxic shock, and necrotizing fasciitis,
      as well as the postinfection sequelae rheumatic fever and rheumatic heart
      disease. This protein is highly conserved among different serotypes and is also
      expressed in human isolates of group B, C, and G streptococci. Human tonsils are
      the primary reservoirs for GAS, maintaining endemic disease across the globe. We
      recently reported that GAS preferentially target nasal mucosa-associated lymphoid
      tissue (NALT) in mice, a tissue functionally analogous to human tonsils.
      Experiments using a C5a peptidase loss-of-function mutant and an intranasal
      infection model showed that this protease is required for efficient colonization
      of NALT. An effective vaccine should prevent infection of this secondary lymphoid
      tissue; therefore, the potential of anti-SCPA antibodies to protect against
      streptococcal infection of NALT was investigated. Experiments showed that GAS
      colonization of NALT was significantly reduced following intranasal immunization
      of mice with recombinant SCPA protein administered alone or with cholera toxin,
      whereas a high degree of GAS colonization of NALT was observed in control mice
      immunized with phosphate-buffered saline only. Moreover, administration of anti
      SCPA serum by the intranasal route protected mice against streptococcal
      infection. These results suggest that intranasal immunization with SCPA would
      prevent colonization and infection of human tonsils, thereby eliminating
      potential reservoirs that maintain endemic disease.

PMID- 16299279
TI  - Conjugates of group A and W135 capsular polysaccharides of neisseria meningitidis
      bound to recombinant Staphylococcus aureus enterotoxin C1: preparation,
      physicochemical characterization, and immunological properties in mice.
AB  - Neisseria meningitidis groups A (GAM) and W135 capsular polysaccharides (CPs)
      were bound to recombinant Staphylococcus aureus enterotoxin C1 (rSEC). The CPs
      were activated with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate and then
      bound to adipic acid dihydrazide derivatives of rSEC. Syntheses were conducted
      with native GAM CP (GAMP), W135 CP (W135P), and ultrasonicated or hydrazine
      treated W135P at various concentrations of reactants, pHs, and ionic strengths.
      The conjugates were characterized by compositional and serologic analyses, high
      performance size-exclusion chromatography with multi-angle laser light scattering
      detection, and immunogenicity in 5- to 6-week-old mice. Conjugates injected
      subcutaneously in phosphate-buffered saline elicited immunoglobulin G (IgG)
      responses against their respective CPs and rSEC, whereas GAMP and W135P alone did
      not induce detectable CP antibodies. The O-acetyl content of W135P was low, and
      its removal had no adverse effect upon the conjugate's immunogenicity. Reduction
      of the molecular size of W135P by treatment with hydrazine improved the
      immunogenicity of W135P-rSEC. IgG anti-CP elicited by the conjugates showed
      complement-dependent bactericidal activity against their respective organisms,
      and IgG anti-rSEC neutralized the T-cell proliferative activity of native SEC. A
      bivalent formulation of GAMP-rSEC and W135P-rSEC elicited IgG anti-CP at
      comparable levels to those induced by the conjugates administered separately.

PMID- 16299280
TI  - Identification of core and variable components of the Salmonella enterica
      subspecies I genome by microarray.
AB  - We have performed microarray hybridization studies on 40 clinical isolates from
      12 common serovars within Salmonella enterica subspecies I to identify the
      conserved chromosomal gene pool. We were able to separate the core invariant
      portion of the genome by a novel mathematical approach using a decision tree
      based on genes ranked by increasing variance. All genes within the core component
      were confirmed using available sequence and microarray information for S.
      enterica subspecies I strains. The majority of genes within the core component
      had conserved homologues in Escherichia coli K-12 strain MG1655. However, many
      genes present in the conserved set which were absent or highly divergent in K-12
      had close homologues in pathogenic bacteria such as Shigella flexneri and
      Pseudomonas aeruginosa. Genes within previously established virulence
      determinants such as SPI1 to SPI5 were conserved. In addition several genes
      within SPI6, all of SPI9, and three fimbrial operons (fim, bcf, and stb) were
      conserved within all S. enterica strains included in this study. Although many
      phage and insertion sequence elements were missing from the core component,
      approximately half the pseudogenes present in S. enterica serovar Typhi were
      conserved. Furthermore, approximately half the genes conserved in the core set
      encoded hypothetical proteins. Separation of the core and variant gene sets
      within S.enterica subspecies I has offered fundamental biological insight into
      the genetic basis of phenotypic similarity and diversity across S. enterica
      subspecies I and shown how the core genome of these pathogens differs from the
      closely related E. coli K-12 laboratory strain.

PMID- 16299281
TI  - Carbohydrate moieties of microsporidian polar tube proteins are targeted by
      immunoglobulin G in immunocompetent individuals.
AB  - Microsporidia of the Encephalitozoon species are frequently found as
      opportunistic pathogens of immunocompromised patients, but very little is known
      about the prevalence and significance of Encephalitozoon infection in
      immunocompetent individuals. It was reported previously that 8% of Dutch blood
      donors and 5% of pregnant French women had an immunoglobulin G (IgG) immune
      response against specific organelles of Encephalitozoon intestinalis. These
      organelles, the so-called polar tube and anchoring disk, are used to penetrate
      membranes of host cells during infection. The unexpectedly high percentage of
      immunocompetent individuals with IgG against these organelles suggested that
      infection of humans with microsporidia might be more common than previously
      recognized. In the present study, we analyzed this anti-Encephalitozoon IgG
      response by using indirect immunofluorescence, Western blotting, two-dimensional
      gel electrophoresis, and chemical deglycosylation. Our results show that the
      antibody response is directed against the posttranslational carbohydrate
      modification of the major polar tube protein (polar tube protein 1) and
      carbohydrate moieties of proteins in the anchoring region of the polar tube of
      Encephalitozoon. In addition, the antibodies were found to decrease the
      infectivity of E. intestinalis in vitro. The significance and possible origin of
      these prevalent antibodies are discussed.

PMID- 16299282
TI  - Syndecan 1 shedding contributes to Pseudomonas aeruginosa sepsis.
AB  - The innate immune system is comprised of many components that function
      coordinately to prevent bacterial sepsis. However, thermal injury suppresses many
      of these factors, and the opportunistic pathogen Pseudomonas aeruginosa takes
      advantage of this condition, making it one of the leading causes of morbidity and
      mortality in the setting of thermal injury. P. aeruginosa is extremely efficient
      at colonizing burn wounds, spreading systemically, and causing sepsis, which
      often results in a systemic inflammatory response, multiple-organ failure, and
      death. The pathogenicity of P. aeruginosa is due to the arsenal of virulence
      factors produced by the pathogen and the immunocompromised state of the host.
      Syndecan 1 is a major heparan sulfate proteoglycan present on many host cells
      involved in thermal injury. Syndecan 1 anchored to the cell surface can be
      cleaved in a process termed ectodomain shedding. Syndecan 1 shedding results in
      the release of intact, soluble proteoglycan ectodomains that have diverse roles
      in innate immunity. Here we show for the first time that thermal injury results
      in shedding of syndecan 1 from host tissue. Our data show that syndecan 1 null
      mice are significantly less susceptible to P. aeruginosa infection than their
      wild-type counterparts, as demonstrated by (i) significantly lower mortality;
      (ii) absence of systemic spread of P. aeruginosa; and (iii) significant
      reductions in some proinflammatory cytokines. These results suggest that shed
      syndecan 1 plays an important role in the pathogenesis of P. aeruginosa infection
      of thermal injury and that syndecan 1-neutralizing agents may be effective
      supplements to current P. aeruginosa treatments.

PMID- 16299283
TI  - Influence of pilin glycosylation on Pseudomonas aeruginosa 1244 pilus function.
AB  - The opportunistic pathogen Pseudomonas aeruginosa is a leading cause of
      nosocomial pneumonia. Among its virulence factors, the type IV pili of P.
      aeruginosa strain 1244 contain a covalently linked, three-sugar glycan of
      previously unknown significance. The work described in this paper was carried out
      to determine the influence of the P. aeruginosa 1244 pilin glycan on pilus
      function, as well as a possible role in pathogenesis. To accomplish this, a
      deletion was introduced into the pilO gene of this organism. The isogenic
      knockout strain produced, 1244G7, was unable to glycosylate pilin but could
      produce pili normal in appearance and quantity. In addition, this strain had
      somewhat reduced twitching motility, was sensitive to pilus-specific
      bacteriophages, and could form a normal biofilm. Analysis of whole cells and
      isolated pili from wild-type P. aeruginosa strain 1244 by transmission electron
      microscopy with a glycan-specific immunogold label showed that this saccharide
      was distributed evenly over the fiber surface. The presence of the pilin glycan
      reduced the hydrophobicity of purified pili as well as whole cells. With regard
      to pathogenicity, P. aeruginosa strains producing glycosylated pili were commonly
      found among clinical isolates and particularly among those strains isolated from
      sputum. Competition index analysis using a mouse respiratory model comparing
      strains 1244 and 1244G7 indicated that the presence of the pilin glycan allowed
      for significantly greater survival in the lung environment. These results
      collectively suggest that the pilin glycan is a significant virulence factor and
      may aid in the establishment of infection.

PMID- 16299284
TI  - Capsule-negative Staphylococcus aureus induces chronic experimental mastitis in
      mice.
AB  - Staphylococcus aureus capsular polysaccharides (CP) have been shown to enhance
      staphylococcal virulence in numerous animal models of infection. Although
      serotype 5 CP (CP5) and CP8 predominate among S. aureus isolates from humans,
      most staphylococcal isolates from bovines with mastitis in Argentina are capsule
      negative. This study was designed to evaluate the effects of CP5 and CP8
      expression on the pathogenesis of experimental murine mastitis. Lactating mice
      were challenged by the intramammary route with one of three isogenic S. aureus
      strains producing CP5, CP8, or no capsule. Significantly greater numbers of
      acapsular mutant cells were recovered from the infected glands 12 days after
      bacterial challenge compared with the encapsulated strains. Histopathological
      analyses revealed greater polymorphonuclear and mononuclear leukocyte
      infiltration and congestion in the mammary glands of mice infected with the
      encapsulated strains compared with the acapsular mutant, and the serotype 5
      strain elicited more inflammation than the serotype 8 strain. In vitro
      experiments revealed that the acapsular S. aureus strain was internalized by MAC
      T bovine epithelial cells in significantly greater numbers than the CP5- or CP8
      producing strain. Taken together, the results suggest that S. aureus lacking a
      capsule was able to persist in the murine mammary gland, whereas encapsulated
      strains elicited more inflammation and were eliminated faster. Loss of CP5 or CP8
      expression may enhance the persistence of staphylococci in the mammary glands of
      chronically infected hosts.

PMID- 16299285
TI  - A leucine-rich motif targets Pseudomonas aeruginosa ExoS within mammalian cells.
AB  - Type III cytotoxins contribute to the ability of bacterial pathogens to subvert
      the host innate immune system. ExoS (453 amino acids) is a bifunctional type III
      cytotoxin produced by Pseudomonas aeruginosa. Residues 96 to 232 comprise a Rho
      GTPase activating protein domain, while residues 233 to 453 comprise a 14-3-3
      dependent ADP-ribosyltransferase domain. An N-terminal domain (termed the
      membrane localization domain [MLD]) targets ExoS to the Golgi-endoplasmic
      reticulum (Golgi-ER) of mammalian cells. This study identifies an amino acid
      motif that is responsible for the membrane binding properties of the MLD.
      Deletion mapping showed that the MLD included a symmetrical leucine-rich motif
      within residues 51 to 77 of ExoS. The terminal dileucines and internal leucines
      and an isoleucine within the MLD, but not charged or other hydrophobic residues,
      targeted a reporter protein to the Golgi-ER region of HeLa cells. Mutations of
      the leucines within the MLD did not affect type III secretion or translocation
      into HeLa cells but limited the ability of ExoS to ADP-ribosylate Ras GTPases.
      Mutations of charged residues within the MLD did not affect type III secretion,
      delivery into HeLa cells, or the ability of ExoS to ADP-ribosylate Ras GTPases.
      The organization of the leucines within the MLD of ExoS is different from that of
      previously described leucine-rich motifs but is present in several other
      bacterial proteins. This implies a role for intracellular targeting in the
      efficient targeting of mammalian cells by type III cytotoxins.

PMID- 16299286
TI  - Tissue destruction induced by Porphyromonas gingivalis infection in a mouse
      chamber model is associated with host tumor necrosis factor generation.
AB  - Intrachamber challenge with Porphyromonas gingivalis strain 381 in a mouse
      subcutaneous chamber model results in a local infection that progresses to
      exfoliation of the chambers within 15 days. This study was designed to elucidate
      the contribution of host reactions to tissue destruction manifested by chamber
      exfoliation in animals infected with P. gingivalis. Chamber fluids showed
      increasing levels of prostaglandin E(2) with infection, and the levels of tumor
      necrosis factor (TNF) in chamber fluids peaked just before chamber exfoliation.
      Intraperitoneal injection of a TNF inhibitor, thalidomide (TH), reduced the
      number of exfoliated chambers, while indomethacin had no effect. Exogenous TNF in
      chambers without bacterial infection did not cause chamber exfoliation but
      induced neutrophil infiltration. In a dual-chamber model, two chambers were
      implanted in the same mouse. One chamber was infected with P. gingivalis, and 9
      days later exogenous TNF was added to the other chamber. Altogether, 66.67% of
      uninfected chambers were exfoliated between day 11 and day 16, although no
      bacteria were recovered from uninfected chambers. TH treatment alleviated both
      infected and uninfected chamber exfoliation. In this study, tissue destruction
      caused by P. gingivalis 381 infection was due to the elevation of the TNF levels
      and not due to local bacterial activities. Our results further indicate that
      local infection by P. gingivalis 381, a nondisseminating strain, actually has
      systemic effects on the host pathological outcome.

PMID- 16299287
TI  - Increased sensitivity to Salmonella enterica serovar Typhimurium infection in
      mice undergoing withdrawal from morphine is associated with suppression of
      interleukin-12.
AB  - We have shown previously that withdrawal from morphine induces immunosuppression
      in mice. The present study reports the effects of morphine withdrawal on
      infection with Salmonella enterica serovar Typhimurium. Mice were made dependent
      on morphine by the implantation of a slow-release morphine pellet for 96 h.
      Controls received a placebo pellet. Withdrawal was induced by pellet removal.
      Mice were inoculated intraperitoneally with Salmonella 24 h postwithdrawal.
      Morphine withdrawal sensitized mice to Salmonella infection, as evidenced by
      increased mortality, shortened mean survival time, and increased bacterial load
      in the blood, spleen, and liver. Examination of the levels of a panel of
      proinflammatory cytokines in sera of infected, morphine-withdrawn mice showed
      that morphine withdrawal inhibited the elevation of interleukin-12p70 (IL-12p70).
      The production of IL-12p40 in morphine withdrawal mice was also suppressed. The
      administration of exogenous IL-12 significantly decreased the bacterial burden in
      morphine-withdrawn mice. These studies show a correlation between the suppression
      of IL-12 production and a heightened susceptibility to Salmonella infection in
      mice undergoing withdrawal from morphine.

PMID- 16299288
TI  - Type 1 chemokine receptor expression in Chagas' disease correlates with morbidity
      in cardiac patients.
AB  - Chemokines and chemokine receptors (CKRs) control the migration of leukocytes
      during the inflammatory process and are important immunological markers of type 1
      (CCR5 and CXCR3) and type 2 (CCR3 and CCR4) responses. The coexpression of CKRs
      (CCR2, CCR3, CCR5, CXCR3, and CXCR4) and intracellular cytokines (interleukin-10
      [IL-10], IL-4, tumor necrosis factor alpha [TNF-alpha], and gamma interferon [IFN
      gamma]) on T CD4+ and CD8+ peripheral cells from individuals with indeterminate
      (IND) or cardiac (CARD) clinical forms of Chagas' disease after in vitro
      stimulation with Trypanosoma cruzi antigens, were evaluated in this study. The
      percentage of T CD4+ and CD8+ cells coexpressing CCR5 and IFN-gamma, CXCR3 and
      IFN-gamma, and CXCR3 and TNF-alpha were higher in CARD than in IND individuals;
      on the other hand, the percentage of T CD4+ or CD8+ cells coexpressing CCR3 and
      IL-10 or coexpressing CCR3 and IL-4 were lower in CARD individuals than in IND
      individuals. In addition, a significant positive correlation between the
      expression of CCR5 or CXCR3 and IFN-gamma was observed in CARD individuals
      contrasting with a significant positive correlation between the expression of
      CCR3 and IL-4 and of CCR3 and IL-10 in IND patients. These results reinforce the
      hypothesis that a T. cruzi-exacerbated specific type 1 immune response developed
      by CARD chagasic patients is associated with the development of heart pathology.

PMID- 16299289
TI  - Synergistic effect of Nod1 and Nod2 agonists with toll-like receptor agonists on
      human dendritic cells to generate interleukin-12 and T helper type 1 cells.
AB  - A synthetic Nod2 agonist, muramyldipeptide (MDP), and two Nod1 agonists, FK565
      and FK156, mimic the bacterial peptidoglycan moiety and are powerful adjuvants
      that induce cell-mediated immunity, especially delayed-type hypersensitivity. In
      this study, we used human dendritic cell (DC) cultures to examine possible T
      helper type 1 (Th1) responses induced by MDP and FK565/156 in combination with
      various synthetic Toll-like receptor (TLR) agonists, including synthetic lipid A
      (TLR4 agonist), the synthetic triacyl lipopeptide Pam3CSSNA (TLR2 agonist),
      poly(I:C) (TLR3 agonist), and CpG DNA (TLR9 agonist). Immature DCs derived from
      human monocytes expressed mRNAs for Nod1, Nod2, TLR2, TLR3, TLR4, and TLR9. The
      stimulation of DCs with MDP and FK565 in combination with lipid A, poly(I:C), and
      CpG DNA, but not with Pam3CSSNA, synergistically induced interleukin-12 (IL-12)
      p70 and gamma interferon (IFN-gamma), but not IL-18, in culture supernatants and
      induced IL-15 on the cell surface. In correlation with the cytokine induction, an
      upregulation of the mRNA expression of these cytokine genes was observed.
      Notably, IL-12 p35 mRNA expression increased >1,000-fold upon stimulation with
      lipid A plus either MDP or FK565 compared with stimulation with each stimulant
      alone. In contrast, for the expression of CD83 and costimulatory molecules such
      as CD40, CD80, and CD86, no synergistic effects were observed upon stimulation
      with Nod plus TLR agonists. The culture supernatants of DCs stimulated with lipid
      A plus either MDP or FK565 activated human T cells to produce high levels of IFN
      gamma, and the activity was attributable to DC-derived IL-12. These findings
      suggest that Nod1 and Nod2 agonists in combination with TLR3, TLR4, and TLR9
      agonists synergistically induce IL-12 and IFN-gamma production in DCs to induce
      Th1-lineage immune responses.

PMID- 16299291
TI  - Neonatal and maternal immunological responses to conserved epitopes within the
      DBL-gamma3 chondroitin sulfate A-binding domain of Plasmodium falciparum
      erythrocyte membrane protein 1.
AB  - Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates the
      adherence of P. falciparum-infected erythrocytes to placental
      syncytiotrophoblasts via interactions with chondroitin sulfate A (CSA), a
      characteristic of pregnancy-associated malaria. Pregnancy-associated malaria
      predicts increased susceptibility of newborns to malaria, and it is postulated
      that transplacental passage of parasite antigen induces immune regulatory
      activity in the neonate. We wished to examine the immune responsiveness to a CSA
      binding domain of PfEMP1, the DBL-gamma3 domain, in cord and maternal venous
      blood obtained from pregnancies with various histories of P. falciparum
      infection. We assessed in vitro T-cell cytokine and plasma immunoglobulin G (IgG)
      and IgM responses to four peptides corresponding to highly conserved regions of a
      DBL-gamma3 domain common to central African parasite isolates. The presence of
      placental P. falciparum infection at delivery was associated with elevated
      frequencies of DBL-gamma3 peptide-specific CD3+ interleukin-10-positive T cells
      in cord blood, while treatment and clearance of infection prior to delivery was
      associated with elevated frequencies of CD3+ gamma interferon-positive T cells.
      DBL-gamma3 peptide-specific IgM antibodies were detected in 12 of 60 (20%) cord
      plasma samples from those born to mothers with P. falciparum infection during
      pregnancy. Consistent with polyclonal anti-PfEMP1 antibody responses that are
      associated with protection against pregnancy-associated malaria, the presence of
      maternal IgG antibodies with specificity for one of the DBL-gamma3 peptides
      showed a parity-dependent profile. These data demonstrate that peptides
      corresponding to conserved regions of the DBL-gamma3 domain of PfEMP1 are
      immunogenic in P. falciparum-infected mothers and their offspring.

PMID- 16299290
TI  - Deletions of endocytic components VPS28 and VPS32 affect growth at alkaline pH
      and virulence through both RIM101-dependent and RIM101-independent pathways in
      Candida albicans.
AB  - Ambient pH signaling involves a cascade of conserved Rim or Pal products in
      ascomycetous yeasts or filamentous fungi, respectively. Recent evidences in the
      fungi Aspergillus nidulans, Saccharomyces cerevisiae, Yarrowia lipolytica, and
      Candida albicans suggested that components of endosomal sorting complexes
      required for transport (ESCRT) involved in endocytic trafficking were needed for
      signal transduction along the Rim pathway. In this study, we confirm these
      findings with C. albicans and show that Vps28p (ESCRT-I) and Vps32p/Snf7p (ESCRT
      III) are required for the transcriptional regulation of known targets of the Rim
      pathway, such as the PHR1 and PHR2 genes encoding cell surface proteins, which
      are expressed at alkaline and acidic pH, respectively. We additionally show that
      deletion of these two VPS genes, particularly VPS32, has a more drastic effect
      than a RIM101 deletion on growth at alkaline pH and that this effect is only
      partially suppressed by expression of a constitutively active form of Rim101p.
      Finally, in an in vivo mouse model, both vps null mutants were significantly less
      virulent than a rim101 mutant, suggesting that VPS28 and VPS32 gene products
      affect virulence both through Rim-dependent and Rim-independent pathways.

PMID- 16299292
TI  - Chronic Leishmania donovani infection promotes bystander CD8+-T-cell expansion
      and heterologous immunity.
AB  - It has been proposed that long-lived memory T cells generated by vaccination or
      infection reside within a memory compartment that has a finite size.
      Consequently, in a variety of acute infection models interclonal competition has
      been shown to lead to attrition of preexisting memory CD8+ T cells. Contrary to
      expectations, therefore, we found that chronic Leishmania donovani infection of
      Listeria-immune mice results in heightened protection against subsequent Listeria
      challenge. This protection was associated with bystander expansion of Listeria
      specific CD8+ T cells and a bias in these cells toward a central memory T-cell
      phenotype with an enhanced capacity for gamma interferon production. We propose
      that splenomegaly, which is characteristic of visceral leishmaniasis and other
      tropical infections, may help promote heterologous immunity by resetting the size
      of the memory compartment during chronic infection.

PMID- 16299293
TI  - H2-M3 major histocompatibility complex class Ib-restricted CD8 T cells induced by
      Salmonella enterica serovar Typhimurium infection recognize proteins released by
      Salmonella serovar Typhimurium.
AB  - Salmonella enterica serovar Typhimurium causes a typhoid-like disease in mice
      which has been studied extensively as a model for typhoid fever in humans. CD8 T
      cells contribute to protection against S. enterica serovar Typhimurium in mice,
      but little is known about the specificity and major histocompatibility complex
      (MHC) restriction of the response. We report here that CD8 T-cell lines derived
      from S. enterica serovar Typhimurium-infected BALB/c mice lysed bone marrow
      macrophages infected with S. enterica serovar Typhimurium or pulsed with proteins
      from S. enterica serovar Typhimurium culture supernatants. Cytoxicity was beta-2
      microglobulin dependent and largely TAP dependent, although not MHC class Ia
      restricted, as target cells of several different MHC haplotypes were lysed. The
      data suggested the participation of class Ib MHC molecules although no evidence
      for the presence of Qa1-restricted T cells could be found, unlike in previous
      reports. Instead, the T-cell lines lysed H2-M3-transfected fibroblasts infected
      with S. enterica serovar Typhimurium SL3261 or treated with Salmonella culture
      supernatants. Thus, this report increases the number of MHC class Ib antigen
      presenting molecules known for Salmonella antigens to three: Qa-1, HLA-E, and now
      H2-M3. It also expands the range of pathogens that induce H2-M3-restricted CD8 T
      cells to include an example of gram-negative bacteria.

PMID- 16299294
TI  - Essential role for humoral immunity during Ehrlichia infection in immunocompetent
      mice.
AB  - Although cellular immunity is essential for host defense during intracellular
      bacterial infections, humoral immunity can also play a significant role in host
      defense during infection by some intracellular bacteria, including the
      ehrlichiae. Antibodies can protect susceptible SCID mice from fatal Ehrlichia
      chaffeensis infection, an observation that has been hypothesized to involve the
      opsonization of bacteria released from host cells. To determine whether humoral
      immunity plays an essential role during ehrlichia infection in immunocompetent
      mice, we utilized a murine model of fatal monocytotropic ehrlichiosis caused by
      Ixodes ovatus ehrlichia. Mice lacking either B cells or FcgammaRI were unable to
      resolve a low-dose (sublethal) I. ovatus ehrlichia infection, which suggested
      that humoral immunity is essential for resistance. Polyclonal sera generated in
      I. ovatus ehrlichia-infected mice recognized a conserved ehrlichia outer membrane
      protein and, when administered to infected mice, caused a significant decrease in
      bacterial infection. Mice experimentally depleted of complement, or deficient for
      complement receptors 1 and 2, were also susceptible to sublethal I. ovatus
      ehrlichia infection, as were mice that lacked the phox91 subunit of NADPH
      oxidase. The data are consistent with a mechanism whereby bacteria released from
      infected cells are lysed directly by complement or undergo antibody-mediated
      FcgammaR-dependent phagocytosis and subsequent exposure to reactive oxygen
      intermediates. The findings suggest mechanisms whereby antibodies contribute to
      immunity against intracellular bacteria in immunocompetent mice.

PMID- 16299295
TI  - Phase I malaria vaccine trial with a long synthetic peptide derived from the
      merozoite surface protein 3 antigen.
AB  - The C-terminal conserved region of Plasmodium falciparum merozoite surface
      protein 3 (MSP3) is the trigger antigen of a protective immune response mediated
      by cytophilic antibodies. In an open, randomized, two-adjuvant (Montanide ISA
      720, aluminum hydroxide) phase I clinical trial we evaluated the safety and
      immunogenicity of increasing doses of a long synthetic peptide construct spanning
      the conserved region of MSP3 targeted by biologically active antibodies (MSP3
      LSP). Thirty-five healthy volunteers were randomized to receive three
      subcutaneous injections on days 0, 30, and 120. Of the 100 injections given, 10
      caused severe local reactions, 62 caused transient mild to moderate local
      reactions, and 28 caused no reaction. On the basis of preestablished exclusion
      criteria, use of the Montanide formulation led to withdrawal of five volunteers
      after the second injection. This led to a reduction in the subsequent vaccine
      doses in four of the groups. No vaccine-related serious adverse events occurred
      throughout the trial. After the third injection, volunteers displayed a marked
      specific anti-MSP3-LSP antibody response (23/30 individuals, compared with 29/34
      individuals for plasma from an area where malaria is endemic), an anti-native
      MSP3 antibody response (19/30 individuals), a T-cell-antigen-specific
      proliferative response (26/30 individuals), and gamma interferon production
      (25/30 individuals). In conclusion, the MSP3-LSP vaccine was immunogenic with
      both adjuvants, although it was unacceptably reactogenic when it was combined
      with Montanide. The potential usefulness of the candidate vaccine is supported by
      the induction of a strong cytophilic response (i.e., the type of anti-MSP3
      antibodies involved in antibody-dependent, monocyte-mediated protective
      mechanisms in areas where malaria is endemic).

PMID- 16299296
TI  - Community-based safety, immunogenicity, and transmissibility study of the
      Shigella sonnei WRSS1 vaccine in Israeli volunteers.
AB  - We describe the first community-based evaluation of Shigella sonnei strain WRSS1,
      a live, oral candidate vaccine attenuated by a 212-bp deletion in the virG (or
      icsA) plasmid virulence gene. Three single-dose regimens of WRSS1 (5 x 10(3) CFU,
      2 x 10(4) CFU, and 4 x 10(5) CFU) were tested with cohorts of 15 adult
      volunteers. The vaccine was generally well tolerated at the 10(3)- and 10(4)-CFU
      doses. There were no fevers and there was one report of moderate diarrhea in 30
      vaccinees; five additional vaccinees reported mild diarrhea. At the 10(5)-CFU
      dose, there were two reports of low-grade fevers and four reports of moderate
      diarrhea. The geometric means for immunoglobulin A (IgA) antibody-secreting cells
      (ASC) against lipopolysaccharide (LPS) were 30, 75, and 193 ASC per 10(6)
      peripheral blood mononuclear cells (PBMC) for the 10(3)-, 10(4)-, and 10(5)-CFU
      doses, respectively. The IgG means were 40, 46, and 135 ASC per 10(6) PBMC,
      respectively. The 10(4)-CFU dose of WRSS1 gave the best balance of safety and
      immunogenicity, since all vaccinees had a significant IgA ASC response and 73%
      had a response of more than 50 ASC. The anti-LPS seroconversion rate (threefold)
      for IgA was 60% and the IgG rate was 27% for the 10(4)-CFU cohort. Each vaccinee
      and a cohabitating household contact delivered daily perianal stool swabs for
      bacteriological culture. WRSS1 colonized vaccinees for a median of 5 days, and
      one individual excreted WRSS1 intermittently for 23 days. None of the 45
      household contacts were colonized with WRSS1 after a cumulative 192 days of
      cohabitation with colonized vaccinees, suggesting that adventitious vaccine
      spread was not common in the community setting.

PMID- 16299297
TI  - DltABCD- and MprF-mediated cell envelope modifications of Staphylococcus aureus
      confer resistance to platelet microbicidal proteins and contribute to virulence
      in a rabbit endocarditis model.
AB  - The DltABCD and MprF proteins contribute a net positive charge to the
      Staphylococcus aureus surface envelope by alanylating and lysinylating teichoic
      acids and membrane phosphatidylglycerol, respectively. These surface charge
      modifications are associated with increased in vitro resistance profiles of S.
      aureus to a number of endogenous cationic antimicrobial peptides (CAPs), such as
      alpha-defensins. The current study investigated the effects of dltA and mprF
      mutations on the following host factors relevant to endovascular infections: (i)
      in vitro susceptibility to the CAP thrombin-induced platelet microbicidal protein
      1 (tPMP-1), (ii) in vitro adherence to endothelial cells (EC) and matrix
      proteins, and (iii) in vivo virulence in an endovascular infection model (rabbit
      endocarditis) in which tPMP-1 is felt to play a role in limiting S. aureus
      pathogenesis. Both mutations resulted in substantial increases in the in vitro
      susceptibility to tPMP-1 compared to that of the parental strain. The dltA (but
      not the mprF) mutation resulted in a significantly reduced capacity to bind to EC
      in vitro, while neither mutation adversely impacted in vitro binding to
      fibronectin, fibrinogen, or platelets. In vivo, both mutations significantly
      attenuated virulence in terms of early colonization of sterile vegetations and
      subsequent proliferation at this site (versus the parental strain). However, only
      the dltA mutation significantly reduced metastatic infections in kidneys and
      spleens compared to those in animals infected with the parental strain. These
      data underscore the importance of resistance to distinct CAPs and of teichoic
      acid-dependent EC interactions in the context of endovascular infection
      pathogenesis.

PMID- 16299298
TI  - Mouse intestine selects nonmotile flhDC mutants of Escherichia coli MG1655 with
      increased colonizing ability and better utilization of carbon sources.
AB  - D-gluconate which is primarily catabolized via the Entner-Doudoroff (ED) pathway,
      has been implicated as being important for colonization of the streptomycin
      treated mouse large intestine by Escherichia coli MG1655, a human commensal
      strain. In the present study, we report that an MG1655 Deltaedd mutant defective
      in the ED pathway grows poorly not only on gluconate as a sole carbon source but
      on a number of other sugars previously implicated as being important for
      colonization, including L-fucose, D-gluconate, D-glucuronate, N-acetyl-D
      glucosamine, D-mannose, and D-ribose. Furthermore, we show that the mouse
      intestine selects mutants of MG1655 Deltaedd and wild-type MG1655 that have
      improved mouse intestine-colonizing ability and grow 15 to 30% faster on the
      aforementioned sugars. The mutants of MG1655 Deltaedd and wild-type MG1655
      selected by the intestine are shown to be nonmotile and to have deletions in the
      flhDC operon, which encodes the master regulator of flagellar biosynthesis.
      Finally, we show that DeltaflhDC mutants of wild-type MG1655 and MG1655 Deltaedd
      constructed in the laboratory act identically to those selected by the intestine;
      i.e., they grow better than their respective parents on sugars as sole carbon
      sources and are better colonizers of the mouse intestine.

PMID- 16299299
TI  - Sensitization of human aortic endothelial cells to lipopolysaccharide via
      regulation of Toll-like receptor 4 by bacterial fimbria-dependent invasion.
AB  - Toll-like receptors (TLRs) are differentially up-regulated in response to
      microbial infection and chronic inflammatory diseases such as atherosclerosis.
      Epidemiological data support the idea that periodontal disease may be a risk
      factor for acceleration of atherosclerosis. Porphyromonas gingivalis, the
      etiological agent of periodontal disease, invades endothelium, has been detected
      in human atheromatous tissue, and accelerates atheroma formation in
      apolipoprotein E-/- mice with concurrent induction of TLRs in the aorta. As
      endothelial cells can present antigen via TLRs and play an important role in the
      development of atherosclerosis, we examined TLR expression in human aortic
      endothelial cells (HAEC) cultured with wild-type P. gingivalis, a fimbria
      deficient mutant, and purified antigens. We observed increased TLR expression in
      HAEC infected with wild-type P. gingivalis by fluorescence-activated cell sorter,
      but not with noninvasive, fimbria-deficient mutant or purified P. gingivalis
      antigens. Following a wild-type P. gingivalis challenge, functional TLR2 and TLR4
      activation was assessed by subsequent stimulation with TLR agonists
      Staphylococcus aureus lipoteichoic acid (SLTA; TLR2 ligand) and Escherichia coli
      lipopolysaccharide (LPS; TLR4 ligand). Unchallenged HAEC failed to elicit
      monocyte chemoattractant protein 1 (MCP-1) in response to LPS or SLTA but did so
      when cultured with wild-type P. gingivalis. P. gingivalis-induced TLR2 and -4
      expression on HAEC functionally reacted to SLTA and E. coli LPS as measured by a
      further increase in MCP-1 production. Furthermore, MCP-1 expression elicited by
      E. coli LPS was inhibitable with TLR4-specific antibody and polymyxin B. These
      results indicate that invasive P. gingivalis stimulates TLR expression on the
      surface of endothelium and these primed cells respond to defined TLR-specific
      ligands.

PMID- 16299300
TI  - Toxoplasma gondii-specific immunoglobulin M limits parasite dissemination by
      preventing host cell invasion.
AB  - An important role for immunoglobulin M (IgM) during early acute virulent
      Toxoplasma gondii infection was identified using IgM-/- mice that lack surface
      and secretory IgM but maintain normal B-cell functionality and isotype class
      switching. Following intraperitoneal inoculation with the virulent RH strain, IgM
      /- mice displayed significantly fewer peritoneal parasites than wild-type (WT)
      mice, which correlated with increased tachyzoite dissemination to the liver,
      lung, and spleen in IgM-/- mice compared with WT mice. Early splenic T-cell
      activation, as measured by CD69 expression, was augmented in IgM-/- mice, and
      serum and peritoneal cavity gamma interferon levels were also elevated in IgM-/-
      mice compared with WT controls. Consequently, the difference in parasite
      dissemination was not attributable to an impaired proinflammatory immune response
      in the IgM-/- mice. Specific IgM was found to bind to tachyzoites in vivo in WT
      mice, and this correlated with an increased ability of antiserum collected from
      WT mice at day 6 postinfection to block tachyzoite cell invasion, compared with
      comparable serum collected from IgM-/- mice at the same time point. Tachyzoite
      invasion of host cells was similar if parasites were incubated with WT or IgM-/-
      nonimmune serum, suggesting that natural IgM does not function to limit parasite
      dissemination during early T. gondii infection. Our results highlight an
      important role for parasite-specific IgM in limiting systemic dissemination of
      tachyzoites during early acute T. gondii infection.

PMID- 16299301
TI  - Virulence and karyotype analyses of rad52 mutants of Candida albicans:
      regeneration of a truncated chromosome of a reintegrant strain (rad52/RAD52) in
      the host.
AB  - The virulence of Candida albicans mutants lacking one or both copies of RAD52, a
      gene involved in homologous recombination (HR), was evaluated in a murine model
      of hematogenously disseminated candidiasis. In this study, the virulence of the
      rad52Delta mutant was dependent upon the inoculum concentration. Mice survived at
      a cell inoculum of 1 x 10(6), but there was a decrease in survival time at
      dosages of 1.5 x 10(6) and especially at 3 x 10(6) cells per animal. The
      heterozygote RAD52/rad52 behaved like wild type, whereas a reintegrant strain was
      intermediate in its ability to cause death compared to these strains and to the
      avirulent rad52/rad52 null at inocula of 1 x 10(6) and 1.5 x 10(6) cells. A
      double mutant, lig4/lig4/rad52/rad52, was avirulent at all inocula used. PCR
      analysis of the RAD52 and/or LIG4 loci showed that all strains recovered from
      animals matched the genotype of the inoculated strains. Analysis of the
      electrophoretical karyotypes indicated that the inoculated, reintegrant strain
      carried a large deletion in one copy of chromosome 6 (the shortest homologue, or
      Chr6b). Interestingly, truncated Chr6b was regenerated in all the strains
      recovered from moribund animals using the homologue as a template. Further,
      regeneration of Chr6b was paralleled by an increase in virulence that was still
      lower than that of wild type, likely because of the persistent loss of
      heterozygosity in the regenerated region. Overall, our results indicate that
      systemic candidiasis can develop in the absence of HR, but simultaneous
      elimination of both recombination pathways, HR and nonhomologous end-joining,
      suppresses virulence even at very high inocula.

PMID- 16299302
TI  - Vaccination with the recombinant Brucella outer membrane protein 31 or a derived
      27-amino-acid synthetic peptide elicits a CD4+ T helper 1 response that protects
      against Brucella melitensis infection.
AB  - The immunogenicity and protective efficacy of the recombinant 31-kDa outer
      membrane protein from Brucella melitensis (rOmp31), administered with incomplete
      Freund's adjuvant, were evaluated in mice. Immunization of BALB/c mice with
      rOmp31 conferred protection against B. ovis and B. melitensis infection. rOmp31
      induced a vigorous immunoglobulin G (IgG) response, with higher IgG1 than IgG2
      titers. In addition, spleen cells from rOmp31-immunized mice produced interleukin
      2 (IL-2) and gamma interferon, but not IL-10 or IL-4, after in vitro stimulation
      with rOmp31, suggesting the induction of a T helper 1 (Th1) response. Splenocytes
      from rOmp31-vaccinated animals also induced a specific cytotoxic-T-lymphocyte
      activity, which led to the in vitro lysis of Brucella-infected macrophages. In
      vitro T-cell subset depletion indicated that rOmp31 immunization elicited
      specific CD4+ T cells that secrete IL-2 and gamma interferon, while CD8+ T cells
      induced cytotoxic-T-lymphocyte activity. In vivo depletion of T-cell subsets
      showed that the rOmp31-elicited protection against B. melitensis infection is
      mediated by CD4+ T cells while the contribution of CD8+ T cells may be limited.
      We then evaluated the immunogenicity and protective efficacy of a known exposed
      region from Omp31 on the Brucella membrane, a peptide that contains amino acids
      48 to 74 of Omp31. Immunization with the synthetic peptide in adjuvant did not
      elicit a specific humoral response but elicited a Th1 response mediated by CD4+ T
      cells. The peptide in adjuvant induced levels of protection similar to those
      induced by rOmp31 against B. melitensis but less protection than was induced by
      rOmp31 against B. ovis. Our results indicate that rOmp31 could be a useful
      candidate for the development of subunit vaccines against B. melitensis and B.
      ovis.

PMID- 16299303
TI  - Early transcriptional response of human neutrophils to Anaplasma phagocytophilum
      infection.
AB  - Anaplasma phagocytophilum, an unusual obligate intracellular pathogen that
      persists within neutrophils, causes human anaplasmosis (previously known as human
      granulocytic ehrlichiosis). To study the effects of this pathogen on the
      transcriptional profile of its host cell, we performed a comprehensive DNA
      microarray analysis of the early (4-h) transcriptional response of human
      neutrophils to A. phagocytophilum infection. A. phagocytophilum infection
      resulted in the up- and down-regulation of 177 and 67 neutrophil genes,
      respectively. These data were verified by quantitative reverse transcription-PCR
      of selected genes. Notably, the up-regulation of many antiapoptotic genes,
      including the BCL2A1, BIRC3, and CFLAR genes, and the down-regulation of the
      proapoptotic TNFSF10 gene were observed. Genes involved in inflammation, innate
      immunity, cytoskeletal remodeling, and vesicular transport also exhibited
      differential expression. Vascular endothelial growth factor was also induced.
      These data suggest that A. phagocytophilum may alter selected host pathways in
      order to facilitate its survival within human neutrophils. To gain further
      insight into the bacterium's influence on host cell gene expression, this report
      presents a detailed comparative analysis of our data and other gene expression
      profiling studies of A. phagocytophilum-infected neutrophils and promyelocytic
      cell lines.

PMID- 16299304
TI  - Global virulence regulation in Staphylococcus aureus: pinpointing the roles of
      ClpP and ClpX in the sar/agr regulatory network.
AB  - Staphylococcus aureus causes infections ranging from superficial wound infections
      to life-threatening systemic infections. Essential for S. aureus pathogenicity
      are a number of cell-wall-associated and secreted proteins that are controlled by
      a complex regulatory network involving the quorum-sensing agr locus and a large
      set of transcription factors belonging to the Sar family. Recently, we revealed a
      new layer of regulation by showing that mutants lacking the ClpXP protease
      produce reduced amounts of several extracellular virulence factors and that,
      independently of ClpP, ClpX is required for transcription of spa, encoding
      Protein A. Here we find that the independent effect of ClpX is not general for
      other cell wall proteins, as expression of fibronectin- and fibrinogen-binding
      proteins was increased in the absence of either ClpX or ClpP. To assess the roles
      of ClpX and ClpP within the sar/agr regulatory network, deletions in clpX and
      clpP were combined with mutations in these genes. Interestingly, the derepression
      of spa transcription normally observed in an agr-negative strain was abolished in
      cells devoid of ClpX, and apparently ClpX modulates both SarS-dependent and SarS
      independent control of spa expression, perhaps through the Sar family member Rot.
      Examination of expression of a single secreted protein, the SspA serine protease,
      revealed that ClpXP, similar to agr, is required for growth phase-dependent
      transcriptional induction of sspa. Intriguingly, induction was restored by the
      concomitant inactivation of Rot. We hypothesize that RNAIII accumulating in the
      postexponential phase may target Rot for degradation by ClpXP, leading to
      derepression of sspA.

PMID- 16299305
TI  - Identification of novel antigenic proteins in a complex Anaplasma marginale outer
      membrane immunogen by mass spectrometry and genomic mapping.
AB  - Immunization with purified Anaplasma marginale outer membranes induces complete
      protection against infection that is associated with CD4+ T-lymphocyte-mediated
      gamma interferon secretion and immunoglobulin G2 (IgG2) antibody titers. However,
      knowledge of the composition of the outer membrane immunogen is limited. Recent
      sequencing and annotation of the A. marginale genome predicts at least 62 outer
      membrane proteins (OMP), enabling a proteomic and genomic approach for
      identification of novel OMP by use of IgG serum antibody from outer membrane
      vaccinates. Outer membrane proteins were separated by two-dimensional
      electrophoresis, and proteins recognized by total IgG and IgG2 in immune sera of
      outer membrane-vaccinated cattle were detected by immunoblotting. Immunoreactive
      protein spots were excised and subjected to liquid chromatography-tandem mass
      spectrometry. A database search of the A. marginale genome identified 24
      antigenic proteins that were predicted to be outer membrane, inner membrane, or
      membrane-associated proteins. These included the previously characterized surface
      exposed outer membrane proteins MSP2, operon associated gene 2 (OpAG2), MSP3, and
      MSP5 as well as recently identified appendage-associated proteins. Among the 21
      newly described antigenic proteins, 14 are annotated in the A. marginale genome
      and include type IV secretion system proteins, elongation factor Tu, and members
      of the MSP2 superfamily. The identification of these novel antigenic proteins
      markedly expands current understanding of the composition of the protective
      immunogen and provides new candidates for vaccine development.

PMID- 16299307
TI  - Th2-associated local reactions to the acellular diphtheria-tetanus-pertussis
      vaccine in 4- to 6-year-old children.
AB  - Acellular vaccines against diphtheria-tetanus-pertussis (acellular pertussis)
      (DTaP) are being progressively introduced into vaccination programs worldwide,
      with the aim of reducing T-helper 1 (Th1)-associated reactogenicity associated
      with the cellular diphtheria-tetanus-pertussis (whole-cell pertussis) (DTwP)
      vaccine. The DTaP vaccine has an improved safety profile in infants, but little
      information is available concerning the nature of the ensuing immunological
      memory in older children and how this may affect the reactogenicity of DTaP
      booster doses. We have addressed this question in the present study by assessing
      polyclonal and vaccine antigen-specific humoral and cellular immune responses to
      boosting with DTaP in 4- to 6-year-old children primed during infancy with DTaP
      (n = 30) or DTwP (n = 16) and by correlating these parameters, in particular
      cytokine responses, with expression of local side effects at the injection site.
      Large local reactions (> or =50-mm diameter) 24 to 72 h after receiving the DTaP
      booster occurred in 43% of exclusively DTaP-primed children, in contrast to 6% of
      children primed with DTwP. These reactions were associated with vigorous T helper
      2 (Th2)-polarized memory responses to vaccine antigen exemplified by interleukin
      5 (IL-5), IL-6, and IL-13 production and log-scale boosting of tetanus-specific
      immunoglobulin E and occurred most frequently among children who are
      intrinsically "high Th2 responders" as detected by in vitro responsiveness to
      polyclonal mitogen. Our findings suggest that priming during infancy with DTaP
      promotes stable, boostable Th2-polarized immunity against vaccine antigens, which
      in a significant subset of children is subsequently associated with local
      reactions at the booster site. The time course of these reactions suggests that
      the underlying mechanism involves reactivation of Th2-polarized cellular immune
      memory.

PMID- 16299306
TI  - Epitope-specific regulation of immunoglobulin class switching in mice immunized
      with malarial merozoite surface proteins.
AB  - Antibodies that bind to Fc receptors and activate complement are implicated in
      the efficient control of pathogens, but the processes that regulate their
      induction are still not well understood. To investigate antigen-dependent factors
      that regulate class switching, we have developed an in vivo model of class
      switching to immunoglobulin G2b (IgG2b) using the malaria antigen Plasmodium
      falciparum merozoite surface protein 2 (MSP2). C57BL/6 mice were immunized with
      recombinant proteins representing discrete domains of MSP2, and a T-cell epitope
      (C8) was identified within the conserved C terminus of the protein that
      preferentially induces IgG2b antibodies. The ability of C8 to induce IgG2b is
      ablated in both homozygous gamma interferon-negative and interleukin 10-negative
      mice. The IgG2b-inducing properties of C8 override the IgG1-inducing properties
      of both the fusion protein partner, glutathione S-transferase, and the adjuvant.
      Furthermore, when attached to other proteins that normally induce IgG1 responses,
      C8 induces a switch to IgG2b secretion. This is the first description of a
      defined T-cell epitope that drives specific IgG2b subclass switching, and our
      data offer proof of the concept that chimeric vaccines incorporating specific T
      cell "switch epitopes" might be used to enhance qualitative aspects of the
      antibody response.

PMID- 16299308
TI  - Regulation of cellular caveolin-1 protein expression in murine macrophages by
      microbial products.
AB  - Previously, we reported that expression of caveolin-1 in elicited peritoneal
      mouse macrophages was up-regulated by remarkably low (1.0-pg/ml) concentrations
      of Escherichia coli O111 lipopolysaccharide (LPS). Here we report that increases
      in caveolin-1 expression are manifested by different types of LPS, LPS-mimetic
      taxol, and heat-killed E. coli and to a much lesser extent by zymosan,
      polysaccharide-peptidoglycan, and heat-killed Staphylococcus aureus. Rhodobacter
      sphaeroides lipid A (RsDPLA) could not induce caveolin-1 expression in
      macrophages. Interestingly, polymyxin B (5 microg/ml) and RsDPLA show only a
      limited capacity to inhibit LPS-induced caveolin-1 expression. These findings
      suggest that expression of caveolin-1 in response to LPS may only partially be
      dependent upon lipid A. Recombinant tumor necrosis factor alpha marginally
      induces caveolin-1, suggesting that the ability of LPS to regulate caveolin-1 is
      not mediated primarily through an autocrine/paracrine mechanism involving this
      cytokine. Under conditions in which cellular levels of caveolin-1 are profoundly
      induced, no significant changes in TLR4 expression are observed. Of interest,
      caveolin-1 appears to localize to two cellular compartments, one associated with
      lipid rafts and a second associated with TLR4. Gamma interferon treatment
      inhibits the induction of caveolin-1 by LPS in macrophages. Inhibition of the p38
      kinase-dependent pathway, but not the extracellular signal-regulated kinase
      pathway, effectively reduced the ability of LPS to mediate caveolin-1 up
      regulation. Lactacystin, a potent inhibitor of the proteasome pathway,
      significantly modulates LPS-independent caveolin-1 expression, and lactacystin
      inhibits LPS-triggered caveolin-1 responses. These studies suggest that caveolin
      1 up-regulation in response to LPS is likely to be proteasome dependent and
      triggered through the p38 kinase pathway.

PMID- 16299309
TI  - Comparative toll-like receptor 4-mediated innate host defense to Bordetella
      infection.
AB  - Bordetella pertussis, B. parapertussis, and B. bronchiseptica are closely related
      species associated with respiratory disease in humans and other mammals. While B.
      bronchiseptica has a wide host range, B. pertussis and B. parapertussis evolved
      separately from a B. bronchiseptica-like progenitor to naturally infect only
      humans. Despite very different doubling times in vitro, all three establish
      similar levels of infection in the mouse lung within 72 h. Recent work has
      revealed separate roles for Toll-like receptor 4 (TLR4) in immunity to B.
      pertussis and B. bronchiseptica, while no role for TLR4 during B. parapertussis
      infection has been described. Here we compared the requirement for TLR4 in innate
      host defense to these organisms using the same mouse infection model. While B.
      bronchiseptica causes lethal disease in TLR4-deficient mice, B. pertussis and B.
      parapertussis do not. Correspondingly, TLR4 is critical in limiting B.
      bronchiseptica but not B. pertussis or B. parapertussis bacterial numbers during
      the first 72 h. Interestingly, B. bronchiseptica induces a TLR4-dependent
      cytokine response that is considerably larger than that induced by B. pertussis
      or B. parapertussis. Analysis of their endotoxins using RAW cells suggests that
      B. bronchiseptica lipopolysaccharide (LPS) is 10- and 100-fold more stimulatory
      than B. pertussis or B. parapertussis LPS, respectively. The difference in LPS
      stimulus is more pronounced when using HEK293 cells expressing human TLR4. Thus,
      it appears that in adapting to infect humans, B. pertussis and B. parapertussis
      independently modified their LPS to reduce TLR4-mediated responses, which may
      compensate for slower growth rates and facilitate host colonization.

PMID- 16299310
TI  - Vaccination with the Chlamydia trachomatis major outer membrane protein can
      elicit an immune response as protective as that resulting from inoculation with
      live bacteria.
AB  - BALB/c mice were vaccinated by the intramuscular (i.m.) and subcutaneous (s.c.)
      routes with a native preparation of the Chlamydia trachomatis mouse pneumonitis
      (MoPn) major outer membrane protein (MOMP), using Montanide ISA 720 and CpG-1826
      as adjuvants. A negative control group was immunized with ovalbumin and the two
      adjuvants, and a positive control group was immunized intranasally (i.n.) with
      10(4) inclusion-forming units (IFU) of C. trachomatis. Four weeks after the last
      i.m.-plus-s.c. immunization, mice were challenged in the ovarian bursa with 10(5)
      IFU of C. trachomatis MoPn. Six weeks after the genital challenge, animals were
      mated, and the pregnancies were monitored. After vaccination with MOMP, the mice
      developed strong Chlamydia-specific humoral and cellular immune responses.
      Following the genital challenge, of the mice vaccinated with the MOMP, only 15%
      (3/20) had positive vaginal cultures, while 85% (17/20) of the animals immunized
      with ovalbumin had positive cultures over the 6 weeks of observation (P < 0.05).
      Also, only 14% (3/21) of the animals inoculated i.n. with Chlamydia had positive
      vaginal cultures. After mating, 75% (15/20) of the mice vaccinated with MOMP
      carried embryos in both uterine horns. Of the animals vaccinated i.n. with the
      Chlamydia, 81% (17/21) had embryos in both uterine horns (P > 0.05). In contrast,
      only 10% (2/20) of the mice immunized with ovalbumin had embryos in both uterine
      horns (P < 0.05). In conclusion, immunization with a purified preparation of the
      MOMP is as effective as vaccination with viable C. trachomatis in eliciting a
      protective immune response against a genital challenge in mice.

PMID- 16299311
TI  - Antigenic specificity of the mucosal antibody response to Moraxella catarrhalis
      in chronic obstructive pulmonary disease.
AB  - Moraxella catarrhalis is an important human mucosal pathogen causing otitis media
      in children and lower respiratory tract infection in adults with chronic
      obstructive pulmonary disease (COPD). Little is known about the mucosal antibody
      response to M. catarrhalis in adults with COPD. In this study, 10 pairs of well
      characterized sputum supernatant samples from adults with COPD who had acquired
      and subsequently cleared M. catarrhalis from their respiratory tracts were
      studied in detail in an effort to begin to elucidate potentially protective
      immune responses. Flow cytometry analysis was used to study the distribution of
      immunoglobulin isotypes in paired preacquisition and postclearance sputum
      samples. The results showed that immunoglobulin A (IgA) is the predominant M.
      catarrhalis-specific immunoglobulin isotype and that the sputum IgA contains a
      secretory component, indicating that it is locally produced at the mucosal site.
      Most patients made new sputum IgA responses to the adhesins UspA1 and Hag, along
      with the surface protein UspA2. A smaller proportion of patients made new sputum
      IgA responses to the iron-regulated proteins TbpB and CopB and to
      lipooligosaccharide. These results have important implications in understanding
      the mucosal immune response to M. catarrhalis in the setting of COPD and in
      elucidating the elements of a protective immune response.

PMID- 16299312
TI  - Iron and fur regulation in Vibrio cholerae and the role of fur in virulence.
AB  - Regulation of iron uptake and utilization is critical for bacterial growth and
      for prevention of iron toxicity. In many bacterial species, this regulation
      depends on the iron-responsive master regulator Fur. In this study we report the
      effects of iron and Fur on gene expression in Vibrio cholerae. We show that Fur
      has both positive and negative regulatory functions, and we demonstrate Fur
      independent regulation of gene expression by iron. Nearly all of the known iron
      acquisition genes were repressed by Fur under iron-replete conditions. In
      addition, genes for two newly identified iron transport systems, Feo and Fbp,
      were found to be negatively regulated by iron and Fur. Other genes identified in
      this study as being induced in low iron and in the fur mutant include those
      encoding superoxide dismutase (sodA), fumarate dehydratase (fumC),
      bacterioferritin (bfr), bacterioferritin-associated ferredoxin (bfd), and
      multiple genes of unknown function. Several genes encoding iron-containing
      proteins were repressed in low iron and in the fur mutant, possibly reflecting
      the need to reserve available iron for the most critical functions. Also
      repressed in the fur mutant, but independently of iron, were genes located in the
      V. cholerae pathogenicity island, encoding the toxin-coregulated pilus (TCP), and
      genes within the V. cholerae mega-integron. The fur mutant exhibited very weak
      autoagglutination, indicating a possible defect in expression or assembly of the
      TCP, a major virulence factor of V. cholerae. Consistent with this observation,
      the fur mutant competed poorly with its wild-type parental strain for
      colonization of the infant mouse gut.

PMID- 16299313
TI  - Ectophosphorylation of CD36 regulates cytoadherence of Plasmodium falciparum to
      microvascular endothelium under flow conditions.
AB  - The adhesion of Plasmodium falciparum-infected erythrocytes (IRBCs) to human
      dermal microvascular endothelial cells (HDMECs) under flow conditions is
      regulated by a Src family kinase- and alkaline phosphatase (AP)-dependent
      mechanism. In this study, we showed that the target of the phosphatase activity
      is the ectodomain of CD36 at threonine-92 (Thr92). Mouse fibroblasts (NIH 3T3
      cells) transfected with wild-type CD36 or a mutant protein in which Thr92 was
      substituted by Ala supported the rolling and adhesion of IRBCs. However, while
      the Src family kinase inhibitors PP1 and PP2 and the specific AP inhibitor
      levamisole significantly reduced IRBC adhesion to wild-type CD36 transfectants as
      with HDMECs, the inhibitors had no effect on IRBC adhesion to the mutant cells.
      Using a phosphospecific antibody directed at a 12-amino-acid peptide spanning
      Thr92, we demonstrated directly that CD36 was constitutively phosphorylated and
      could be dephosphorylated by exogenous AP. Endothelial CD36 was likewise
      constitutively phosphorylated. The phosphospecific antibody inhibited IRBC
      adhesion to HDMECs that could be reversed by preincubating the antibody with the
      phosphorylated but not the nonphosphorylated peptide. Pretreatment of HDMECs with
      AP abrogated the effect of PP1 on IRBC adhesion. Collectively, these results are
      consistent with a critical role for CD36 dephosphorylation through Src family
      kinase activation in regulating IRBC adhesion to vascular endothelium.

PMID- 16299314
TI  - Relative roles of complement factor 3 and mannose-binding lectin in host defense
      against infection.
AB  - Staphylococcus aureus is a major cause of severe nosocomial and community
      acquired infections. Phagocytes and humoral molecules, including complement, have
      been proposed to cooperate in host defense against gram-positive bacteria.
      Circumstantial evidence indicates a role for complement, but this has not been
      formally defined. Complement activation is initiated by the classical,
      alternative, or lectin pathway, with the latter requiring mannose-binding lectin
      (MBL, also known as mannose-binding protein). MBL is an oligomeric serum protein
      that recognizes carbohydrates decorating a broad range of infectious agents,
      including S. aureus. We previously reported that MBL null mice were highly
      susceptible to S. aureus infection, confirming that MBL plays a key role in first
      line host defense. In this study, we evaluated the relative roles of C3 and MBL
      against S. aureus infection by generating MBL x C3 null mice to compare with C3
      single null mice. C3 deficiency alone significantly reduced survival to 19% from
      97% of wild-type mice (P < 0.0001). Surprisingly, an additional MBL deficiency
      reduced the survival further to 7% (P < 0.0001). However, the MBL deficiency
      alone had a smaller though significant effect on survival, which was 77% (P =
      0.018 versus wild-type mice). These results confirm an essential function for
      complement in host resistance against S. aureus infection but also identify an
      MBL-dependent mechanism that is C3 independent.

PMID- 16299315
TI  - Novel attenuated Salmonella enterica serovar Choleraesuis strains as live vaccine
      candidates generated by signature-tagged mutagenesis.
AB  - Salmonella enterica serovar Choleraesuis is a host-adapted pathogen that causes
      swine paratyphoid. Signature-tagged mutagenesis (STM) was used to understand the
      pathogenicity of S. enterica serovar Choleraesuis in its natural host and also to
      develop novel attenuated live vaccine candidates against this disease. A library
      of 960 signature-tagged mutants of S. enterica serovar Choleraesuis was
      constructed and screened for attenuation in pigs. Thirty-three mutants were
      identified by the STM screening, and these mutants were further screened for
      attenuation by in vivo and in vitro competitive growth. Of these, 20 mutants
      targeting the outer membrane, type III secretion, transporter, lipopolysaccharide
      biosynthesis, and other unknown proteins were confirmed for attenuation. Five
      highly attenuated mutants (SC2D2 [ssaV], SC4A9 [gifsy-1], SC6F9 [dgoT], SC12B12
      [ssaJ], and SC10B1[spiA]) were selected and evaluated for safety and protective
      efficacy in pigs by comparison with a commercially available vaccine strain. STM
      attenuated live vaccine strains SC4A9 (gifsy-1) and SC2D2 (ssaV) were superior to
      commercially available live vaccine because they provided both safety and a
      protective immune response against challenge in pigs.

PMID- 16299316
TI  - Giardia lamblia-induced changes in gene expression in differentiated Caco-2 human
      intestinal epithelial cells.
AB  - The parasitic protozoan Giardia lamblia is a worldwide cause of diarrhea, but the
      mechanism of disease remains elusive. The parasite colonizes the small intestinal
      epithelium, known to be a sensor for the presence of enteric pathogens, without
      invading or causing severe inflammation. In this study we investigated the
      epithelial cell response to G. lamblia. Differentiated Caco-2 cells were infected
      with G. lamblia isolate WB-A11, and the transcriptome of the intestinal cells was
      analyzed after 1.5, 6, and 18 h of interaction, using oligonucleotide
      microarrays. A large number of genes displayed changed expression patterns,
      showing the complexity of the interaction between G. lamblia and intestinal
      cells. A novel chemokine profile (CCL2, CCL20, CXCL1, CXCL2, and CXCL3) was
      induced that was different from the response induced by enteric pathogens causing
      intestinal inflammation. Several genes involved in stress regulation changed
      their expression. These findings indicate that the intestinal epithelium senses
      the G. lamblia infection, and this is important for induction of innate and
      adaptive immunity. The induced stress response can be important in the
      pathogenesis.

PMID- 16299317
TI  - Anaplasma phagocytophilum delay of neutrophil apoptosis through the p38 mitogen
      activated protein kinase signal pathway.
AB  - Human granulocytic anaplasmosis is caused by the obligate intracellular bacterium
      Anaplasma phagocytophilum. The bacterium avoids host innate defenses in part by
      infecting, surviving in, and propagating in neutrophils, as well as by inhibiting
      neutrophil apoptosis. However, the mechanisms of A. phagocytophilum survival in
      neutrophils and the inhibition of spontaneous apoptosis are not well understood.
      In this study, we demonstrated that antiapoptotic Mcl-1 protein (Bcl-2 family)
      expression is maintained and that inhibition of procaspase-3 processing occurs in
      A. phagocytophilum-infected human neutrophils. An evaluation of p38 mitogen
      activated protein kinase (MAPK) showed evidence of increased phosphorylation with
      infection. Moreover, antagonism of p38 MAPK by the inhibitor SB203580 reversed
      apoptosis inhibition in live or heat-killed A. phagocytophilum-infected
      neutrophils. A role for the autocrine or paracrine production of antiapoptotic
      interleukin 8 (IL-8) expressed with A. phagocytophilum infection was excluded by
      the use of IL-8-, IL-8R1 (CXCR1)-, and IL-8R2 (CXCR2)-blocking antibodies. As
      previously demonstrated, the antiapoptotic effect was initially mediated by
      exposure to A. phagocytophilum components in heat-killed bacteria. However, an
      important role for active infection is demonstrated by the additional delay in
      apoptosis with intracellular growth and the refractory abrogation of this
      response by the p38 MAPK inhibitor 3 to 6 h after neutrophil infection. These
      results suggest that the initial activation of the p38 MAPK pathway leading to A.
      phagocytophilum-delayed neutrophil apoptosis is bypassed with active
      intracellular infection. Moreover, active intracellular infection contributes
      more to the overall delay in apoptosis than do components of heat-killed A.
      phagocytophilum alone.

PMID- 16299318
TI  - Cryptococcus neoformans gene involved in mammalian pathogenesis identified by a
      Caenorhabditis elegans progeny-based approach.
AB  - Caenorhabditis elegans can serve as a substitute host for the study of microbial
      pathogenesis. We found that mutations in genes of the fungal pathogen
      Cryptococcus neoformans involved in mammalian virulence allow C. elegans to
      produce greater numbers of progeny than when exposed to wild-type fungus. We used
      this property to screen a library of C. neoformans mutants for strains that
      permit larger C. elegans brood sizes. In this screen, we identified a gene
      homologous to Saccharomyces cerevisiae ROM2. C. neoformans rom2 mutation resulted
      in a defect in mating and growth defects at elevated temperature or in the
      presence of cell wall or hyperosmolar stresses. An effect of the C. neoformans
      rom2 mutation in virulence was confirmed in a murine inhalation infection model.
      We propose that a screen for progeny-permissive mutants of microorganisms can
      serve as a high-throughput method for identifying novel loci related to mammalian
      pathogenesis.

PMID- 16299319
TI  - Interferon-inducible protein 10, but not monokine induced by gamma interferon,
      promotes protective type 1 immunity in murine Klebsiella pneumoniae pneumonia.
AB  - CXC chemokines that lack the ELR motif, including interferon-inducible protein 10
      [IP-10 (CXCL10)] and monokine induced by gamma interferon (IFN-gamma) [MIG
      (CXCL9)], have been shown to mediate the generation of type 1 immune responses.
      In this study, we found that intrapulmonary administration of the gram-negative
      bacterium Klebsiella pneumoniae resulted in the local and systemic expression of
      IP-10, followed sequentially by MIG expression. MIG mRNA expression in the lungs
      of Klebsiella-infected mice required the endogenous production of IFN-gamma,
      whereas IP-10 was expressed in both an IFN-gamma-dependent and an IFN-gamma
      independent fashion. Antibody-mediated neutralization of IP-10 resulted in
      reduced bacterial clearance and decreased survival, whereas bacterial clearance
      was unaltered in mice treated with anti-MIG antibody. Impaired bacterial
      clearance in anti-IP-10 antibody-treated mice was associated with significant
      reductions in the number and/or activational status of NK and NK-T cells, CD4+ T
      cells, and gammadelta T cells, as well as a reduction in the expression of IFN
      gamma. Conversely, the transient transgenic expression of murine IP-10 using
      adenovirus-mediated gene transfer resulted in improved bacterial clearance when
      IP-10 adenovirus was given concomitant with intrapulmonary bacterial challenge.
      These results indicate that IP-10 is an important component of innate immunity
      against extracellular bacterial pathogens of the lung and may represent a
      candidate molecule for immunotherapy in the setting of severe respiratory tract
      infection.

PMID- 16299320
TI  - Roles of specific amino acids in the N terminus of Pseudomonas aeruginosa
      flagellin and of flagellin glycosylation in the innate immune response.
AB  - The Toll-like receptor 5 (TLR5) binding site has been predicted to be in the N
      terminus of the flagellin molecule. In order to better define the interaction
      between the N-terminal amino acids of Pseudomonas aeruginosa flagellin and TLR5,
      site-specific mutations were generated between residues 88 and 97 of P.
      aeruginosa PAK flagellin as well as outside of this region. The mutant flagellins
      were expressed in Escherichia coli BL21(plysS), purified by affinity
      chromatography, and passed through a polymyxin B column to remove contaminating
      lipopolysaccharide (LPS). Their ability to stimulate interleukin-8 (IL-8) release
      from A549 cells was examined. The cloned mutated genes were used to complement a
      PAK fliC mutant in order to test for effects on motility and on IL-8 release by
      purified flagellar preparations. All the mutations, single or double, in the
      predicted TLR5 binding region reduced IL-8 signaling to less than 95% of the wild
      type flagellin levels, but the single mutation outside the binding region had no
      effect. Changes made at two amino acid sites resulted in loss/reduction of
      motility; however, changes made at single sites, i.e., Q83A, L88A, R90A, M91A,
      L94A, and Q97A, had no effect on motility. The mutated genes encoding two of the
      motile but poorly signaling flagellins had no compensatory mutations to allow
      motility. Thus, while it is speculated that pathogen-associated molecular
      patterns (PAMPs) have evolved in locations that are essential to maintain
      function, it appears that there is tolerance for at least single amino acid
      changes in the PAMP of P. aeruginosa flagellin. The purpose of flagellin
      glycosylation in P. aeruginosa is unknown. In order to examine its role, if any,
      in signaling an inflammatory response, we used whole flagella from the motile
      chromosomal mutant strains PAKrfbC and PAO1rfbC, which are defective in flagellin
      glycosylation. IL-8 release from A549 cells stimulated with nonglycosylated
      flagellar preparations (having less then 1 picogram of LPS/mug) was significantly
      reduced compared to their respective wild-type flagellar preparations, indicating
      a role of flagellar glycosylation in the proinflammatory action of Pseudomonas
      flagellin. The basis of the latter activity is unknown, since the glycosylation
      sites are found in the D3 domain of flagellins and the TLR5 binding site is
      located in the D1 domain. Thus, P. aeruginosa flagellin has evolved additional
      flagellar signaling mechanisms over that described for Salmonella flagellin.

PMID- 16299321
TI  - Cold shock response of the UspA1 outer membrane adhesin of Moraxella catarrhalis.
AB  - Colonization of the human nasopharynx exposes Moraxella catarrhalis, a common
      cause of otitis media in children and exacerbations of chronic obstructive
      pulmonary disease in adults, to sudden downshifts in temperature, occurring when
      the host breathes cold air. We investigated whether in vitro cold shock
      influences the expressions of the outer membrane adhesins UspA1 and
      hemagglutinin, which are considered virulence factors, and of an M. catarrhalis
      homolog of recA, a housekeeping gene, which in Escherichia coli is induced by
      cold shock. Quantitative real-time reverse transcriptase PCR was used for
      measuring mRNA copy number. A screening experiment revealed that a cold shock at
      26 degrees C maximally induced the copy number of uspA1. In comparison with 37
      degrees C conditions, a 1-hour cold shock at 26 degrees C increased copy numbers
      of uspA1 and recA by 2.5-fold (11.2 +/- 1.8 versus 4.5 +/- 0.8 copies/CFU) and
      2.7-fold (0.30 +/- 0.10 versus 0.11 +/- 0.06), respectively, but did not induce
      transcription of hag. Exposure to 26 degrees C increased surface expression of
      UspA1, as assessed by fluorescence-activated cell sorter analysis, and resulted
      in a significant increase in adherence of strain O35E to Chang human conjunctival
      cells (97.1% +/- 2.0% versus 48.3% +/- 9.2% at 37 degrees C; P = 0.01). Cold
      shock induction of uspA1 and recA was detected in strains belonging to either
      phylogenetic subpopulation of M. catarrhalis (16S rRNA types 1 and 2/3) and was
      most pronounced in type 2/3 strains (4- to 25-fold for uspA1), which do not
      express detectable amounts of UspA1 protein at 37 degrees C. These data indicate
      that cold shock at a physiologically relevant temperature of 26 degrees C induces
      the expression of at least one virulence factor (UspA1). To our knowledge, no
      similar data are available for other nasopharyngeal pathogens.

PMID- 16299322
TI  - Induction of protective serum meningococcal bactericidal and diphtheria
      neutralizing antibodies and mucosal immunoglobulin A in volunteers by nasal
      insufflations of the Neisseria meningitidis serogroup C polysaccharide-CRM197
      conjugate vaccine mixed with chitosan.
AB  - Thirty-six healthy volunteers received either a single intramuscular injection of
      Neisseria meningitidis serogroup C polysaccharide (MCP)-CRM197 conjugate vaccine
      in alum or two nasal insufflations 28 days apart of the same vaccine powder,
      without alum, mixed with chitosan. Nasal immunization was well tolerated, with
      fewer symptoms reported than after intramuscular injection. The geometric mean
      concentrations of MCP-specific immunoglobulin G (IgG) after one nasal
      immunization were 3.25 microg/ml in naive subjects and 14.4 microg/ml in subjects
      previously immunized parenterally, compared with 4.30 microg/ml in naive subjects
      immunized intramuscularly. The geometric mean titer of serum bactericidal
      antibody (SBA) rose 24-fold after two nasal immunizations in naive subjects and
      was comparable to parenteral immunization (1,080 versus 1,625). All subjects
      achieved SBA titers associated with protection after two nasal immunizations:
      even those with titers of <8 at entry. A single nasal immunization boosted the
      SBA titer to > or =128 in 96% of previously immunized subjects, and two
      immunizations achieved this level in 92% of naive subjects. MCP-specific IgG
      levels were approximately 70% IgG2 and approximately 20% IgG1 after nasal or
      intramuscular immunization. Increases in CRM197-specific IgG and diphtheria toxin
      neutralizing activity were observed after nasal or intramuscular immunization,
      with balanced IgG1/IgG2 and higher IgG4. Significant MCP-specific secretory IgA
      was detected in nasal wash only after nasal immunization and predominantly on the
      immunized side. Simple nasal insufflation of existing MCP-CRM197 conjugate
      vaccines in chitosan offers an inexpensive but effective needle-free prime and
      boost against serogroup C N. meningitidis and diphtheria.

PMID- 16299323
TI  - Plant-based vaccine: mice immunized with chloroplast-derived anthrax protective
      antigen survive anthrax lethal toxin challenge.
AB  - The currently available human vaccine for anthrax, derived from the culture
      supernatant of Bacillus anthracis, contains the protective antigen (PA) and
      traces of the lethal and edema factors, which may contribute to adverse side
      effects associated with this vaccine. Therefore, an effective expression system
      that can provide a clean, safe, and efficacious vaccine is required. In an effort
      to produce anthrax vaccine in large quantities and free of extraneous bacterial
      contaminants, PA was expressed in transgenic tobacco chloroplasts by inserting
      the pagA gene into the chloroplast genome. Chloroplast integration of the pagA
      gene was confirmed by PCR and Southern analysis. Mature leaves grown under
      continuous illumination contained PA as up to 14.2% of the total soluble protein.
      Cytotoxicity measurements in macrophage lysis assays showed that chloroplast
      derived PA was equal in potency to PA produced in B. anthracis. Subcutaneous
      immunization of mice with partially purified chloroplast-derived or B. anthracis
      derived PA with adjuvant yielded immunoglobulin G titers up to 1:320,000, and
      both groups of mice survived (100%) challenge with lethal doses of toxin. An
      average yield of about 150 mg of PA per plant should produce 360 million doses of
      a purified vaccine free of bacterial toxins edema factor and lethal factor from 1
      acre of land. Such high expression levels without using fermenters and the
      immunoprotection offered by the chloroplast-derived PA should facilitate
      development of a cleaner and safer anthrax vaccine at a lower production cost.
      These results demonstrate the immunogenic and immunoprotective properties of
      plant-derived anthrax vaccine antigen.

PMID- 16299324
TI  - Direct inhibition of T-lymphocyte activation by anthrax toxins in vivo.
AB  - The causative agent of anthrax, Bacillus anthracis, produces two toxins that
      contribute in part to its virulence. Lethal toxin is a metalloprotease that
      cleaves upstream mitogen-activated protein kinase kinases. Edema toxin is a
      calmodulin-dependent adenylate cyclase. Previous studies demonstrated that the
      anthrax toxins are important immunomodulators that promote immune evasion of the
      bacterium by suppressing activation of macrophages and dendritic cells. Here we
      showed that injection of sublethal doses of either lethal or edema toxin into
      mice directly inhibited the subsequent activation of T lymphocytes by T-cell
      receptor-mediated stimulation. Lymphocytes were isolated from toxin-injected mice
      after 1 or 4 days and stimulated with antibodies against CD3 and CD28. Treatment
      with either toxin inhibited the proliferation of T cells. Injection of lethal
      toxin also potently inhibited cytokine secretion by stimulated T cells. The
      effects of edema toxin on cytokine secretion were more complex and were dependent
      on the length of time between the injection of edema toxin and the isolation of
      lymphocytes. Treatment with lethal toxin blocked multiple kinase signaling
      pathways important for T-cell receptor-mediated activation of T cells.
      Phosphorylation of the extracellular signal-regulated kinase and the stress
      activated kinase p38 was significantly decreased. In addition, phosphorylation of
      the serine/threonine kinase AKT and of glycogen synthase kinase 3 was inhibited
      in T cells from lethal toxin-injected mice. Thus, anthrax toxins directly act on
      T lymphocytes in a mouse model. These findings are important for future anthrax
      vaccine development and treatment.

PMID- 16299325
TI  - Noncapsulated Klebsiella pneumoniae bearing mannose-containing O antigens is
      rapidly eradicated from mouse lung and triggers cytokine production by
      macrophages following opsonization with surfactant protein D.
AB  - To better understand the relationship between the surface polysaccharides of
      pulmonary pathogens and components of the lung innate immune system, we employed
      selected serotypes of Klebsiella pneumoniae expressing distinct capsular
      polysaccharides and/or O antigen in a murine model of K. pneumoniae infection. In
      addition, we examined the effect of surfactant protein D (SP-D) on the cytokine
      response of human monocyte-derived macrophages to these serotypes in vitro.
      Noncapsulated mannose-containing O3 serotypes (K50/n and K55/n), which react
      efficiently with SP-D in vitro, triggered high levels of interleukin-1beta (IL
      1beta) and IL-6 production. In vivo, they were more efficiently cleared from the
      lungs of mice but not from macrophage-depleted mice. They also were more
      efficiently internalized by alveolar macrophages in vivo. In contrast, galactose
      containing O1 serotypes (K2/n and K21a/n), which interact poorly with SP-D,
      exhibited significantly lower cytokine production and less efficient pulmonary
      clearance and were ineffectively internalized by alveolar macrophages. These
      findings are consistent with in vitro results showing that production of IL-1beta
      and IL-6 mRNA and IL-6 protein by human macrophages exposed to mannose-bearing
      Klebsiella O serotypes is significantly increased by SP-D. Thus, survival of
      inhaled bacteria in the lung depends partially on the lipopolysaccharide
      structure of the bacteria and their interactions with innate immunity components.
      We speculate that an imbalance of host SP-D and therefore cytokine levels may
      result in high susceptibility of the host to the pathogen.

PMID- 16299326
TI  - Protective immunity to the larval stages of onchocerca volvulus is dependent on
      Toll-like receptor 4.
AB  - Toll-like receptor 4 (TLR4) has been shown to be important for the induction of
      Th2-dependent immune responses in mice. Protective immunity against larval
      Onchocerca volvulus in mice depends on the development of a Th2 immune response
      mediated by both interleukin-4 (IL-4) and IL-5. In addition, O. volvulus contains
      the rickettsial endosymbiont Wolbachia, which has molecules with
      lipopolysaccharide-like activities that also signal through TLR4. We therefore
      hypothesized that protective immunity to O. volvulus would not develop in C3H/HeJ
      mice which have a mutation in the Tlr4 gene (TLR4 mutant), either because of a
      decreased Th2 response to the larvae or because of the absence of a response to
      Wolbachia. TLR4-mutant mice were immunized against O. volvulus with irradiated
      third-stage larvae, and it was observed that Th2 responses were elevated based on
      increased IL-5 production, total immunoglobulin E (IgE) levels, antigen-specific
      IgG1 response, and eosinophil recruitment. Protective immunity, however, did not
      develop in the TLR4-mutant mice. The Th1 response, as measured by gamma
      interferon production from spleen cells, was comparable in both wild-type and
      TLR4-mutant mice. Furthermore, antibody responses to Wolbachia were absent in
      both wild-type and TLR4-mutant mice. Therefore, the defect in the development of
      a protective immune response against O. volvulus in TLR4-mutant mice is not due
      to loss of Th2 immunity or the response to Wolbachia but is due to an
      unidentified TLR4-dependent larval killing mechanism.

PMID- 16299327
TI  - Pseudomonas aeruginosa acquires biofilm-like properties within airway epithelial
      cells.
AB  - Pseudomonas aeruginosa can notably cause both acute and chronic infection. While
      several virulence factors are implicated in the acute phase of infection,
      advances in understanding bacterial pathogenesis suggest that chronic P.
      aeruginosa infection is related to biofilm formation. However, the relationship
      between these two forms of disease is not well understood. Accumulating evidence
      indicates that, during acute infection, P. aeruginosa enters epithelial cells, a
      process viewed as either a host-mediated defense response or a pathogenic
      mechanism to avoid host-mediated killing. We investigated the possibility that
      epithelial cell entry during early P. aeruginosa-epithelial cell contact favors
      bacterial survival and is linked to chronic infection. Using electron microscopy
      and confocal microscopy to analyze primary culture airway epithelial cells
      infected with P. aeruginosa, we found that epithelial cells developed pod-like
      clusters of intracellular bacteria with regional variation in protein expression.
      Extracellular gentamicin added to the medium after acute infection led to the
      persistence of intracellular P. aeruginosa for at least 3 days. Importantly,
      compared to bacterial culture under planktonic conditions, the intracellular
      bacteria were insensitive to growth inhibition or killing by antibiotics that
      were capable of intraepithelial cell penetration. These findings suggest that P.
      aeruginosa can use airway epithelial cells as a sanctuary for persistence and
      develop a reversible antibiotic resistance phenotype characteristic of biofilm
      physiology that can contribute to development of chronic infection.

PMID- 16299329
TI  - Specific-pathogen-free pigs as an animal model for studying Chlamydia trachomatis
      genital infection.
AB  - The purpose of the present study was to evaluate pigs as a large-animal model for
      female genital infection with two Chlamydia trachomatis human serovar E strains.
      Sixteen-week-old specific-pathogen-free female pigs (gilts) were intravaginally
      infected with the trachoma type E reference strain Bour or the urogenital serovar
      E strain 468. Several conclusions can be drawn from our findings on the
      pathogenicity of a primary C. trachomatis genital infection in gilts. First of
      all, we demonstrated that the serovar E strains Bour and 468 could ascend in the
      genital tract of gilts. The serovar E strains could replicate in the superficial
      columnar cervical epithelium and in the superficial epithelial layer of the
      uterus, which are known to be the specific target sites for a C. trachomatis
      genital infection in women. Second, inflammation and pathology occurred at the
      replication sites. Third, the organisms could trigger a humoral immune response,
      as demonstrated by the presence of immunoglobulin M (IgM), IgG, and IgA in both
      serum and genital secretion samples. Our findings imply that the pig model might
      be useful for studying the pathology, pathogenesis, and immune response to a C.
      trachomatis infection of the genital system.

PMID- 16299328
TI  - Shiga toxin 2 and lipopolysaccharide induce human microvascular endothelial cells
      to release chemokines and factors that stimulate platelet function.
AB  - Shiga toxins (Stxs) produced by Shigella dysenteriae type 1 and enterohemorrhagic
      Escherichia coli are the most common cause of hemolytic-uremic syndrome (HUS). It
      is well established that vascular endothelial cells, mainly those located in the
      renal microvasculature, are targets for Stxs. The aim of the present research was
      to evaluate whether E. coli-derived Shiga toxin 2 (Stx2) incubated with human
      microvascular endothelial cells (HMEC-1) induces release of chemokines and other
      factors that might stimulate platelet function. HMEC-1 were exposed for 24 h in
      vitro to Stx2, lipopolysaccharide (LPS), or the Stx2-LPS combination, and
      chemokine production was assessed by immunoassay. More interleukin-8 was released
      than stromal cell-derived factor 1alpha (SDF-1alpha) or SDF-1beta and RANTES. The
      Stx2-LPS combination potentiated chemokine release, but Stx2 alone caused more
      release of SDF-1alpha at 24 h than LPS or Stx2-LPS did. In the presence of low
      ADP levels, HMEC-1 supernatants activated platelet function assessed by classical
      aggregometry, single-particle counting, granule secretion, P-selectin exposure,
      and the formation of platelet-monocyte aggregates. Supernatants from HMEC-1
      exposed only to Stx2 exhibited enhanced exposure of platelet P-selectin and
      platelet-THP-1 cell interactions. Blockade of platelet cyclooxygenase by
      indomethacin prevented functional activation. The chemokine RANTES enhanced
      platelet aggregation induced by SDF-1alpha, macrophage-derived chemokine, or
      thymus and activation-regulated chemokine in the presence of very low ADP levels.
      These data support the hypothesis that microvascular endothelial cells exposed to
      E. coli O157:H7-derived Stx2 and LPS release chemokines and other factors, which
      when combined with low levels of primary agonists, such as ADP, cause platelet
      activation and promote the renal thrombosis associated with HUS.

PMID- 16299330
TI  - Leishmania pifanoi amastigotes avoid macrophage production of superoxide by
      inducing heme degradation.
AB  - Whereas infections of macrophages by promastigote forms of Leishmania mexicana
      pifanoi induce the production of superoxide, infections by amastigotes barely
      induce superoxide production. Several approaches were employed to gain insight
      into the mechanism by which amastigotes avoid eliciting superoxide production.
      First, in experiments with nitroblue tetrazolium, we found that 25% of
      parasitophorous vacuoles (PVs) that harbor promastigotes are positive for the
      NADPH oxidase complex, in contrast to only 2% of PVs that harbor amastigotes.
      Second, confocal microscope analyses of infected cells labeled with antibodies to
      gp91phox revealed that this enzyme subunit is found in PVs that harbor
      amastigotes. Third, in immunoblots of subcellular fractions enriched with PVs
      from amastigote-infected cells and probed with antibodies to gp91phox, only the
      65-kDa premature form of gp91phox was found. In contrast, subcellular fractions
      from macrophages that ingested zymosan particles contained both the 91- and 65
      kDa forms of gp91phox. This suggested that only the immature form of gp91phox is
      recruited to PVs that harbor amastigotes. Given that gp91phox maturation is
      dependent on the availability of heme, we found that infections by Leishmania
      parasites induce an increase in heme oxygenase 1 (HO-1), the rate-limiting enzyme
      in heme degradation. Infections by amastigotes performed in the presence of
      metalloporphyrins, which are inhibitors of HO-1, resulted in superoxide
      production by infected macrophages. Taken together, we propose that Leishmania
      amastigotes avoid superoxide production by inducing an increase in heme
      degradation, which results in blockage of the maturation of gp91phox, which
      prevents assembly of the NADPH oxidase enzyme complex.

PMID- 16299331
TI  - Regulation of impaired protein kinase C signaling by chemokines in murine
      macrophages during visceral leishmaniasis.
AB  - The protein kinase C (PKC) family regulates macrophage function involved in host
      defense against infection. In the case of Leishmania donovani infection, the
      impairment of PKC-mediated signaling is one of the crucial events for the
      establishment of parasite into the macrophages. Earlier reports established that
      C-C chemokines mediated protection against leishmaniasis via the generation of
      nitric oxide after 48 h. In this study, we investigated the role of MIP-1alpha
      and MCP-1 in the regulation of impaired PKC activity in the early hours (6 h) of
      infection. These chemokines restored Ca2+-dependent PKC activity and inhibited
      Ca2+-independent atypical PKC activity in L. donovani-infected macrophages under
      both in vivo and in vitro conditions. Pretreatment of macrophages with chemokines
      induced superoxide anion generation by activating NADPH oxidase components in
      infected cells. Chemokine administration in vitro induced the migration of
      infected macrophages and triggered the production of reactive oxygen species. In
      vivo treatment with chemokines significantly restricted the parasitic burden in
      livers as well as in spleens. Collectively, these results indicate a novel
      regulatory role of C-C chemokines in controlling the intracellular growth and
      multiplication of L. donovani, thereby demonstrating the antileishmanial
      properties of C-C chemokines in the disease process.

PMID- 16299332
TI  - A mutant of Francisella tularensis strain SCHU S4 lacking the ability to express
      a 58-kilodalton protein is attenuated for virulence and is an effective live
      vaccine.
AB  - Francisella tularensis subsp. tularensis (type A) strain SCHU S4 is a prototypic
      strain of the pathogen that is highly virulent for humans and other mammals. Its
      intradermal (i.d.) 50% lethal dose (LD50) for mice is <10 CFU. We discovered a
      spontaneous mutant, designated FSC043, of SCHU S4 with an i.d. LD50 of >10(8)
      CFU. FSC043 effectively vaccinated mice against challenge with a highly virulent
      type A strain, and the protective efficacy was at least as good as that of F.
      tularensis LVS, an empirically attenuated strain which has been used as an
      efficacious human vaccine. Comparative proteomics was used to identify two
      proteins of unknown function that were identified as defective in LVS and FSC043,
      and deletion mutants of SCHU S4 were created for each of the two encoding genes.
      One mutant, the DeltaFTT0918 strain, failed to express a 58-kDa protein, had an
      i.d. LD50 of approximately 10(5) CFU, and was found to be less capable than SCHU
      S4 of growing in peritoneal mouse macrophages. Mice that recovered from sublethal
      infection with the DeltaFTT0918 mutant survived when challenged 2 months later
      with >100 LD50s of the highly virulent type A strain FSC033. This is the first
      report of the generation of defined mutants of F. tularensis subsp. tularensis
      and their use as live vaccines.

PMID- 16299333
TI  - Whole-genome analyses of speciation events in pathogenic Brucellae.
AB  - Despite their high DNA identity and a proposal to group classical Brucella
      species as biovars of Brucella melitensis, the commonly recognized Brucella
      species can be distinguished by distinct biochemical and fatty acid characters,
      as well as by a marked host range (e.g., Brucella suis for swine, B. melitensis
      for sheep and goats, and Brucella abortus for cattle). Here we present the genome
      of B. abortus 2308, the virulent prototype biovar 1 strain, and its comparison to
      the two other human pathogenic Brucella species and to B. abortus field isolate 9
      941. The global distribution of pseudogenes, deletions, and insertions supports
      previous indications that B. abortus and B. melitensis share a common ancestor
      that diverged from B. suis. With the exception of a dozen genes, the genetic
      complements of both B. abortus strains are identical, whereas the three species
      differ in gene content and pseudogenes. The pattern of species-specific gene
      inactivations affecting transcriptional regulators and outer membrane proteins
      suggests that these inactivations may play an important role in the establishment
      of host specificity and may have been a primary driver of speciation in the genus
      Brucella. Despite being nonmotile, the brucellae contain flagellum gene clusters
      and display species-specific flagellar gene inactivations, which lead to the
      putative generation of different versions of flagellum-derived structures and may
      contribute to differences in host specificity and virulence. Metabolic changes
      such as the lack of complete metabolic pathways for the synthesis of numerous
      compounds (e.g., glycogen, biotin, NAD, and choline) are consistent with
      adaptation of brucellae to an intracellular life-style.

PMID- 16299334
TI  - Passive protection against anthrax by using a high-affinity antitoxin antibody
      fragment lacking an Fc region.
AB  - Passive immunization has been successfully employed for protection against
      bacterial and viral infections for over 100 years. Immunoglobulin Fc regions play
      a critical role in the clearance of bacterial pathogens by mediating antibody
      dependent and complement-dependent cytotoxicity. Here we show that antibody
      fragments engineered to recognize the protective antigen component of the B.
      anthracis exotoxin with high affinity and conjugated to polyethylene glycol (PEG)
      for prolonged circulation half-life confer significant protection against
      inhalation anthrax despite their lack of Fc regions. The speed and lower
      manufacturing cost of bacterially expressed PEGylated antibody fragments could
      provide decisive advantages for anthrax prophylaxis. Importantly, our results
      suggest that PEGylated antibody fragments may represent a unique approach for
      mounting a rapid therapeutic response to emerging pathogen infections.

PMID- 16299335
TI  - Mycobacterium-induced potentiation of type 1 immune responses and protection
      against malaria are host specific.
AB  - Malaria and tuberculosis are endemic in many regions of the world, and
      coinfection with the two pathogens is common. In this study, we examined the
      effects of long- and short-term infection with Mycobacterium tuberculosis on the
      course of a lethal form of murine malaria in resistant (C57BL/6) and susceptible
      (BALB/c) mice. C57BL/6 mice coinfected with M. tuberculosis CDC1551 and
      Plasmodium yoelii 17XL had a lower peak parasitemia and increased survival
      compared to mice infected with P. yoelii 17XL alone. Splenic microarray analysis
      demonstrated potentiation of type 1 immune responses in coinfected C57BL/6 mice,
      which was especially prominent 5 days after infection with P. yoelii 17XL.
      Splenocytes from coinfected C57BL/6 mice produced higher levels of gamma
      interferon (IFN-gamma) and tumor necrosis factor alpha than splenocytes from mice
      infected with either pathogen alone. Interestingly, mycobacterium-induced
      protection against lethal P. yoelii is mouse strain specific. BALB/c mice were
      significantly more susceptible than C57BL/6 mice to infection with P. yoelii 17XL
      and were not protected against lethal malaria by coinfection with M.
      tuberculosis. In addition, M. tuberculosis did not augment IFN-gamma responses in
      BALB/c mice subsequently infected with P. yoelii 17XL. These data indicate that
      M. tuberculosis-induced potentiation of type 1 immune responses is associated
      with protection against lethal murine malaria.

PMID- 16299336
TI  - Reduction of cell surface glycosylphosphatidylinositol conjugates in Entamoeba
      histolytica by antisense blocking of E. histolytica GlcNAc-phosphatidylinositol
      deacetylase expression: effect on cell proliferation, endocytosis, and adhesion
      to target cells.
AB  - Glycosylphosphatidylinositol (GPI)-anchored molecules such as cell surface
      Gal/GalNAc lectin and proteophosphoglycans of the protozoan parasite Entamoeba
      histolytica are thought to be involved in pathogenesis. Here, we report the
      identification of genes that may be involved in the GPI biosynthetic pathway of
      E. histolytica by use of bioinformatic tools applied to the recently published
      genome sequence. Of the genes identified, one of the early genes, GlcNAc
      phosphatidylinositol deacetylase (PIG-L), was partially characterized. Cell lines
      deficient in E. histolytica PIG-L (EhPL-AS) or overproducing it (EhPL-S) were
      generated by expressing the gene in the antisense or sense orientation,
      respectively, in a tetracycline-inducible system. The overexpressing cells showed
      higher EhPIG-L activity and increased production of GlcN-PI. Conversely, cells
      expressing the antisense RNA displayed reduced GlcN-PI production. The total
      number of GPI-containing molecules was also reduced in these cells, as
      demonstrated by Alexa 488 fluorescently labeled proaerolysin labeling. The
      distribution of GPI-linked PPG and Gal/GalNAc lectin was altered in the
      tetracycline-induced EhPL-AS cell lines. Further, the antisense-blocked cells
      showed 36% suppression of cell growth, 50 to 60% inhibition of fluid phase
      endocytosis, and about 50% inhibition of adhesion to target cells. Therefore, our
      data suggest the importance of GPI anchors in regulating some of the events in
      amoebic pathogenesis. They also demonstrated the use of antisense RNA-mediated
      inhibition of GPI biosynthetic enzymes as an approach to decrease the amount of
      GPI conjugates in E. histolytica.

PMID- 16299337
TI  - Impaired Kupffer cells in highly susceptible mice infected with Trypanosoma
      congolense.
AB  - In highly susceptible BALB/c mice infected with Trypanosoma congolense, the total
      number of Kupffer cells in the liver remains constant; however, their mean size
      increases fivefold towards the terminal stage. About 25% of Kupffer cells undergo
      apoptosis. We suggest that development of an impairment of the macrophage system
      might be a major mechanism for inefficient elimination of trypanosomes.

PMID- 16299338
TI  - Toll-like receptor 2 deficiency delays pneumococcal phagocytosis and impairs
      oxidative killing by granulocytes.
AB  - Phagocytosis and killing of Streptococcus pneumoniae was compared in blood
      derived wild-type (WT) and Toll-like receptor 2 (TLR2)-deficient (TLR2-/-)
      polymorphonuclear leukocytes (PMN). Phagocytosis of green fluorescent protein
      transformed pneumococci was delayed in TLR2-/- PMN. These cells exhibited also a
      lower oxidative bactericidal activity against S. pneumoniae than WT PMN,
      suggesting that TLR2 modulates bacterial clearance in PMN.

PMID- 16299340
TI  - Clostridium perfringens enterotoxin damages the human intestine in vitro.
AB  - In vitro, Clostridium perfringens enterotoxin (CPE) binds to human ileal
      epithelium and induces morphological damage concurrently with reduced short
      circuit current, transepithelial resistance, and net water absorption. CPE also
      binds to the human colon in vitro but causes only slight morphological and
      transport changes that are not statistically significant.

PMID- 16299339
TI  - Intrapulmonary, adenovirus-mediated overexpression of KARAP/DAP12 enhances fungal
      clearance during invasive aspergillosis.
AB  - Herein, we report that the intrapulmonary delivery of an adenovirus vector
      expressing KARAP/DAP12, an adaptor protein expressed in granulocytes and
      mononuclear cells, enhanced fungal clearance during experimental invasive
      pulmonary aspergillosis in neutropenic mice.

PMID- 16299341
TI  - Characterization of two non-locus of enterocyte effacement-encoded type III
      translocated effectors, NleC and NleD, in attaching and effacing pathogens.
AB  - Intestinal colonization by enteropathogenic and enterohemorrhagic Escherichia
      coli requires the locus of enterocyte effacement-encoded type III secretion
      system. We report that NleC and NleD are translocated into host cells via this
      system. Deletion mutants induced attaching and effacing lesions in vitro, while
      infection of calves or lambs showed that neither gene was required for
      colonization.

PMID- 16299342
TI  - High susceptibility of human dendritic cells to invasion by the intracellular
      pathogens Brucella suis, B. abortus, and B. melitensis.
AB  - Bacteria from the Brucella genus are able to survive and proliferate within
      macrophages. Because they are phylogenetically closely related to macrophages,
      myeloid dendritic cells (DCs) constitute potential targets for Brucella bacteria.
      Here we report that DCs display a great susceptibility to Brucella infection.
      Therefore, DCs might serve as a reservoir and be important for the development of
      Brucella bacteria within their host.

PMID- 16299343
TI  - An early intestinal mucosal source of gamma interferon is associated with
      resistance to and control of Cryptosporidium parvum infection in mice.
AB  - Resistance to and control of Cryptosporidium parvum infection in mice in the
      absence of adaptive immunity appears to be gamma interferon (IFN-gamma)
      dependent. Using an IFN-gamma-neutralizing antibody in a murine model, we
      demonstrated increased susceptibility to infection within 24 h. We correlated
      this early resistance and control with increased mucosal expression of IFN-gamma
      and demonstrate that CD8+ T-cell receptor alphabeta intestinal intraepithelial
      lymphocytes express and secrete this cytokine shortly after infection. The rapid
      kinetics of IFN-gamma expression and secretion by naive CD8+ T cells in response
      to a protozoan pathogen have not previously been demonstrated.

PMID- 16299344
TI  - Receptor-mediated clearance of Cryptococcus neoformans capsular polysaccharide in
      vivo.
AB  - Cryptococcus neoformans capsular glucuronoxylomannan (GXM) is shed during
      cryptococcosis and taken up by macrophages. The roles of the putative GXM
      receptors CD14, CD18, Toll-like receptor 2 (TLR2), and TLR4 in GXM clearance from
      serum and deposition in the liver and spleen in receptor-deficient mice were
      studied. While alterations in the kinetics of GXM redistribution were seen in the
      mutant mice, none of the receptors was absolutely required for serum clearance or
      hepatosplenic accumulation.

PMID- 16299345
TI  - Attenuation of Salmonella enterica Serovar Typhimurium by altering biological
      functions of murein lipoprotein and lipopolysaccharide.
AB  - We constructed Salmonella enterica serovar Typhimurium double-knockout mutants in
      which either the lipoprotein A (lppA) or the lipoprotein B (lppB) gene was
      deleted from an msbB-negative background strain by marker exchange mutagenesis.
      These mutants were highly attenuated when tested with in vitro and in vivo models
      of Salmonella pathogenesis.

PMID- 16299346
TI  - Neutralization of tumor necrosis factor alpha suppresses antigen-specific type 1
      cytokine responses and reverses the inhibition of mycobacterial survival in
      cocultures of immune guinea pig T lymphocytes and infected macrophages.
AB  - Neutralization of tumor necrosis factor alpha (TNF-alpha) significantly down
      regulated antigen-induced lymphoproliferation and the expression of interleukin
      12 p40 and gamma interferon mRNA and enhanced the viability of intracellular
      attenuated and virulent mycobacteria in cocultures of immune T cells and
      macrophages obtained from Mycobacterium bovis BCG-vaccinated guinea pigs. This
      suggests the crucial role of TNF-alpha in the activation of a type 1 T-cell
      response against Mycobacterium tuberculosis infection.

PMID- 16299347
TI  - Eosinophils, but not eosinophil peroxidase or major basic protein, are important
      for host protection in experimental Brugia pahangi infection.
AB  - The attenuation of eosinophilia by the administration of monoclonal antibodies to
      CCR3 consistently correlates with impairment in worm elimination following
      primary intraperitoneal Brugia pahangi infections in mice. Host protection was
      unimpaired in mice deficient in eosinophil peroxidase (EPO) or major basic
      protein 1 (MBP-1), suggesting that eosinophils are essential in host protection
      but that neither EPO nor MBP-1 alone is.

PMID- 16299348
TI  - Azurin of pathogenic Neisseria spp. is involved in defense against hydrogen
      peroxide and survival within cervical epithelial cells.
AB  - Laz, a lipid-modified azurin of the human pathogens Neisseria gonorrhoeae and
      Neisseria meningitidis, is involved in defense against oxidative stress and
      copper toxicity; laz mutant strains are hypersensitive to hydrogen peroxide and
      copper. The N. gonorrhoeae laz mutant also has decreased survival in an ex vivo
      primary human ectocervical epithelial assay.

PMID- 16299349
TI  - Different Helicobacter hepaticus strains with variable genomic content induce
      various degrees of hepatitis.
AB  - A 70-kb genomic island (HHGI1) in Helicobacter hepaticus strain ATCC 51449 is a
      putative pathogenicity island (PAI). To determine the in vivo relevance of this
      PAI, we inoculated A/JCr mice with one of three strains of H. hepaticus: type
      strain Hh3B1, which contains the complete PAI, and strains HhNET and HhG, which
      lack all or large parts of HHGI1, respectively. Mice infected with HhG and HhNET
      developed less-severe hepatitis than male A/JCr mice infected with Hh3B1.

PMID- 16299350
TI  - Yersinia enterocolitica invasin-dependent and invasin-independent mechanisms of
      systemic dissemination.
AB  - We report here invasin-dependent and invasin-independent mechanisms in which the
      enteropathogen Yersinia enterocolitica is able to disseminate from the lumen of
      the small intestine to the spleen. The invasin-dependent route is clearly
      discernible in mice devoid of intestinal Peyer's patches and mesenteric lymph
      nodes.

PMID- 16299352
TI  - Metabolic effects of intravenous LCT or MCT/LCT lipid emulsions in preterm
      infants.
AB  - Most lipid emulsions for parenteral feeding of premature infants are based on
      long-chain triacylglycerols (LCTs), but inclusion of medium-chain
      triacylglycerols (MCTs) might provide a more readily oxidizable energy source.
      The influence of these emulsions on fatty acid composition and metabolism was
      studied in 12 premature neonates, who were randomly assigned to an LCT emulsion
      (control) or an emulsion with a mixture of MCT and LCT (1:1). On study day 7, all
      infants received [13C]linoleic (LA) and [13C]alpha-linolenic acid (ALA) tracers
      orally. Plasma phospholipid (PL) and triacylglycerol (TG) fatty acid composition
      and 13C enrichments of plasma PL fatty acids were determined on day 8. After 8
      days of lipid infusion, plasma TGs in the MCT/LCT group had higher contents of
      C8:0 (0.50 +/- 0.60% vs. 0.10 +/- 0.12%; means +/- SD) and C10:0 (0.66 +/- 0.51%
      vs. 0.15 +/- 0.17%) than controls. LA content of plasma PLs was slightly lower in
      the MCT/LCT group (16.47 +/- 1.16% vs. 18.57 +/- 2.09%), whereas long-chain
      polyunsaturated derivatives (LC-PUFAs) of LA and ALA tended to be higher. The
      tracer distributions between precursors and products (LC-PUFAs) were not
      significantly different between groups. Both lipid emulsions achieve similar
      plasma essential fatty acid (EFA) contents and similar proportional conversion of
      EFAs to LC-PUFAs. The MCT/LCT emulsion seems to protect EFAs and LC-PUFAs from
      beta-oxidation.

PMID- 16299351
TI  - Bile salt biotransformations by human intestinal bacteria.
AB  - Secondary bile acids, produced solely by intestinal bacteria, can accumulate to
      high levels in the enterohepatic circulation of some individuals and may
      contribute to the pathogenesis of colon cancer, gallstones, and other
      gastrointestinal (GI) diseases. Bile salt hydrolysis and hydroxy group
      dehydrogenation reactions are carried out by a broad spectrum of intestinal
      anaerobic bacteria, whereas bile acid 7-dehydroxylation appears restricted to a
      limited number of intestinal anaerobes representing a small fraction of the total
      colonic flora. Microbial enzymes modifying bile salts differ between species with
      respect to pH optima, enzyme kinetics, substrate specificity, cellular location,
      and possibly physiological function. Crystallization, site-directed mutagenesis,
      and comparisons of protein secondary structure have provided insight into the
      mechanisms of several bile acid-biotransforming enzymatic reactions. Molecular
      cloning of genes encoding bile salt-modifying enzymes has facilitated the
      understanding of the genetic organization of these pathways and is a means of
      developing probes for the detection of bile salt-modifying bacteria. The
      potential exists for altering the bile acid pool by targeting key enzymes in the
      7alpha/beta-dehydroxylation pathway through the development of pharmaceuticals or
      sequestering bile acids biologically in probiotic bacteria, which may result in
      their effective removal from the host after excretion.

PMID- 16299357
TI  - Vet to be suspended for medicines and supervision offences.

PMID- 16299353
TI  - StpA protein from Escherichia coli condenses supercoiled DNA in preference to
      linear DNA and protects it from digestion by DNase I and EcoKI.
AB  - The nucleoid-associated protein, StpA, of Escherichia coli binds non-specifically
      to double-stranded DNA (dsDNA) and apparently forms bridges between adjacent
      segments of the DNA. Such a coating of protein on the DNA would be expected to
      hinder the action of nucleases. We demonstrate that StpA binding hinders dsDNA
      cleavage by both the non-specific endonuclease, DNase I, and by the site-specific
      type I restriction endonuclease, EcoKI. It requires approximately one StpA
      molecule per 250-300 bp of supercoiled DNA and approximately one StpA molecule
      per 60-100 bp on linear DNA for strong inhibition of the nucleases. These results
      support the role of StpA as a nucleoid-structuring protein which binds DNA
      segments together. The inhibition of EcoKI, which cleaves DNA at a site remote
      from its initial target sequence after extensive DNA translocation driven by ATP
      hydrolysis, suggests that these enzymes would be unable to function on
      chromosomal DNA even during times of DNA damage when potentially lethal,
      unmodified target sites occur on the chromosome. This supports a role for
      nucleoid-associated proteins in restriction alleviation during times of cell
      stress.

PMID- 16299355
TI  - Epidemiological report on avian influenza in birds in quarantine facility in
      Essex.

PMID- 16299354
TI  - Chimeric peptide nucleic acid compounds modulate splicing of the bcl-x gene in
      vitro and in vivo.
AB  - Alternative splicing of the bcl-x gene generates two transcripts: the anti
      apoptotic bcl-xL isoform and the pro-apoptotic bcl-xS isoform. The ratio between
      the two isoforms is a key factor in development and in cancer progression. Here,
      we show that a short antisense chimeric peptide nucleic acid (PNA)
      oligonucleotide conjugated to a polypeptide containing eight Ser-Arg repeats
      (SR)(8) can modulate splicing of bcl-x both in vitro and in vivo and induces
      apoptosis in HeLa cells. The PNA-SR oligo was targeted to a region of bcl-x that
      does not contain splicing regulatory sequences and was able to override the
      complex network of splicing enhancers and silencers that regulates the ratio
      between the two bcl-x isoforms. Thus, PNA-SR oligos are powerful tools that can
      potentially modulate splice site choice in endogenous genes independent of the
      presence of other splicing regulatory mechanisms on the target gene.

PMID- 16299362
TI  - Putting research into practice.

PMID- 16299364
TI  - Molecular evidence of tick-transmitted infections in dogs and cats in the United
      Kingdom.
AB  - PCR analysis was used to determine the prevalence of tick-transmitted infections
      in 120 systemically ill dogs and 60 cats recruited over a period of three months
      from 52 veterinary practices in the UK. The animals had not travelled outside the
      UK and had one or more of the following clinical criteria: acute or recurrent
      pyrexia, anaemia and/or thrombocytopenia, polyarthritis/muscle pain,
      splenomegaly/lymphadenopathy, and intraocular inflammation with systemic signs.
      Blood samples from the animals were tested for the presence of DNA from Borrelia
      burgdorferi sensu lato and Anaplasma phagocytophilum by using simple PCR
      targeting. B. burgdorferi sensu lato was detected in five dogs and two cats, and
      A. phagocytophilum was detected in one dog and one cat. These results provide the
      first molecular evidence of naturally occurring B. burgdorferi sensu lato
      infection in cats in the UK and confirm that A. phagocytophilum infection is
      present in cats. There were no statistically significant associations between the
      infections and the clinical signs shown by the dogs and cats.

PMID- 16299365
TI  - Ultrasonographic assessment of the rate of solid-phase gastric emptying in dogs.
AB  - Twelve healthy dogs were used in an ultrasonographic assessment of the effect of
      the composition of a solid meal on the rate of gastric emptying. The dogs were
      fasted for nine hours before they were fed either a standard or a high energy
      density test meal, in a cross-over study design. The gastric antrum was
      visualised with a 6.5 MHz microconvex transducer, and the area inside the
      elliptical shape defined by the craniocaudal and ventrodorsal diameters of the
      stomach was measured. Antral images were acquired at regular intervals for six
      hours after the ingestion of the test meal. Three indices to describe the rate of
      gastric emptying were computed: the gastric half-emptying time (t1/2), the time
      to 50 per cent maximal antral area (t50%), and the time of maximal antral area
      (tmax). The values of t50% and t1/2 calculated for the high energy density meals
      were significantly longer than for the standard meals, but there was no
      significant difference between the tmax values.

PMID- 16299366
TI  - Slaughterhouse survey of pyelonephritis in dairy cows.
AB  - Twenty-one rejected kidneys from 2426 slaughtered dairy cows (0.87 per cent) had
      gross signs of pyelonephritis that were confirmed by histopathology. In all the
      kidneys the findings were consistent with a chronic rather than an acute
      infection. One species of bacteria was cultured from 12 of the kidneys and two
      species of bacteria were cultured from six. The most commonly isolated bacteria
      were Escherichia coli, from eight kidneys, Arcanobacterium pyogenes, from seven
      kidneys and Corynebacterium renale, from five kidneys. The other bacteria
      cultured were Corynebacterium cystitidis, Corynebacterium species, Streptococcus
      species group G and Enterococcus faecalis. E. coli was cultured from all the
      kidneys from which two species were isolated; the accompanying bacteria were A.
      pyogenes in three kidneys, C. renale in two and C. cystitidis in one. No bacteria
      were cultured from two of the kidneys and no significant bacteria were cultured
      from another. The kidneys with pyelonephritis were slightly larger than a
      comparison group of 72 kidneys without nephritis.

PMID- 16299367
TI  - Role of transcranial magnetic stimulation in differentiating motor nervous tract
      disorders from other causes of recumbency in four horses and one donkey.
AB  - Transcranial magnetic stimulation and measurement of the magnetic motor-evoked
      potentials (MMEPs) in the thoracic and pelvic limbs of four recumbent horses and
      one recumbent donkey were used to assess the integrity of the descending motor
      pathways, in order to confirm or exclude a descending motor tract lesion as the
      cause of the recumbency. In two of the animals abnormal MMEPs were recorded; in
      one of the horses a lesion along the cervical spinal cord due to a fracture of
      the fifth cervical vertebra was diagnosed and confirmed by radiography and
      postmortem examination; in another horse, damage to the peripheral nerves of the
      left forelimb was diagnosed and confirmed postmortem when a large abscess was
      found to have been compressing the peripheral nerves at the level of the last
      cervical vertebra. In the three other animals, normal MMEPs were recorded, and
      laminitis, rhabdomyolysis and physitis were diagnosed as the causes of the
      recumbency.

PMID- 16299368
TI  - Failure to detect transmission of Escherichia coli O157:H7 from orally dosed
      nannies to sucking kids at foot.

PMID- 16299369
TI  - Incidence of lead shot ingestion in red-legged partridges (Alectoris rufa) in
      Great Britain.

PMID- 16299370
TI  - Effect of acupuncture, electroacupuncture and Panax pseudoginseng on blood
      coagulation variables in horses.

PMID- 16299371
TI  - Isolation of mycoplasmas from pigeons suffering eye lesions and respiratory
      disease.

PMID- 16299372
TI  - Atypical scrapie in the Falkland Islands.

PMID- 16299375
TI  - Registration of animals.

PMID- 16299374
TI  - Fire action causes alarm.

PMID- 16299376
TI  - Brucella canis in South Africa.

PMID- 16299377
TI  - Mass spectrometric analysis of the ubiquinol-binding site in cytochrome bd from
      Escherichia coli.
AB  - Cytochrome bd is a heterodimeric terminal ubiquinol oxidase in the aerobic
      respiratory chain of Escherichia coli. For understanding the unique catalytic
      mechanism of the quinol oxidation, mass spectrometry was used to identify amino
      acid residue(s) that can be labeled with a reduced form of 2-azido-3-methoxy-5
      methyl-6-geranyl-1,4-benzoquinone or 2-methoxy-3-azido-5-methyl-6-geranyl-1,4
      benzoquinone. Matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry demonstrated that the photo inactivation of ubiquinol-1 oxidase
      activity was accompanied by the labeling of subunit I with both azidoquinols. The
      cross-linked domain was identified by reverse-phase high performance liquid
      chromatography of subunit I peptides produced by in-gel double digestion with
      lysyl endopeptidase and endoproteinase Asp-N. Electrospray ionization quadrupole
      time-of-flight mass spectrometry determined the amino acid sequence of the
      peptide (m/z 1047.5) to be Glu(278)-Lys(283), where a photoproduct of azido-Q(2)
      was linked to the carboxylic side chain of I-Glu(280). This study demonstrated
      directly that the N-terminal region of periplasmic loop VI/VII (Q-loop) is a part
      of the quinol oxidation site and indicates that the 2- and 3-methoxy groups of
      the quinone ring are in the close vicinity of I-Glu(280).

PMID- 16299378
TI  - Selective role of intracellular chloride in the regulation of the intrinsic but
      not extrinsic pathway of apoptosis in Jurkat T-cells.
AB  - Apoptosis is a genetic program for the removal of unwanted cells from an
      organism, which is distinct from necrosis by its characteristic volume loss or
      apoptotic volume decrease. This cell shrinkage is the result of ion
      redistribution that is crucial for both the activation and execution of
      apoptosis. Here we report that UV-C but not Fas ligand treatment results in a
      significant decrease in intracellular chloride that can be abolished by
      modulation of chloride flux using either the chloride channel inhibitor SITS or
      medium with a reduced chloride concentration. Accordingly, downstream events are
      diminished during UV-C-induced apoptosis following chloride flux modulation,
      whereas Fas ligand-induced apoptotic characteristics are not affected. Moreover,
      the activation of the mitogen-activated protein kinase signal transduction
      pathway early in the apoptotic signaling cascade was affected by chloride flux in
      Jurkat T-cells. Thus, an alteration of intracellular chloride plays an important
      role in the activation of signaling molecules upstream of the mitochondria,
      specifically impairing the intrinsic but not extrinsic apoptotic pathway.

PMID- 16299380
TI  - Central role of the scaffold protein tumor necrosis factor receptor-associated
      factor 2 in regulating endoplasmic reticulum stress-induced apoptosis.
AB  - The endoplasmic reticulum represents the quality control site of the cell for
      folding and assembly of cargo proteins. A variety of conditions can alter the
      ability of the endoplasmic reticulum (ER) to properly fold proteins, thus
      resulting in ER stress. Cells respond to ER stress by activating different signal
      transduction pathways leading to increased transcription of chaperone genes,
      decreased protein synthesis, and eventually to apoptosis. In the present paper we
      analyzed the role that the adaptor protein tumor necrosis factor-receptor
      associated factor 2 (TRAF2) plays in regulating cellular responses to apoptotic
      stimuli from the endoplasmic reticulum. Mouse embryonic fibroblasts derived from
      TRAF2-/- mice were more susceptible to apoptosis induced by ER stress than the
      wild type counterpart. This increased susceptibility to ER stress-induced
      apoptosis was because of an increased accumulation of reactive oxygen species
      following ER stress, and was abolished by the use of antioxidant. In addition, we
      demonstrated that the NF-kappaB pathway protects cells from ER stress-induced
      apoptosis, controlling ROS accumulation. Our results underscore the involvement
      of TRAF2 in regulating ER stress responses and the role of NF-kappaB in
      protecting cells from ER stress-induced apoptosis.

PMID- 16299381
TI  - Scanning the membrane-bound conformation of helix 1 in the colicin E1 channel
      domain by site-directed fluorescence labeling.
AB  - Helix 1 of the membrane-associated closed state of the colicin E1 channel domain
      was studied by site-directed fluorescence labeling where bimane was covalently
      attached to a single cysteine residue in each mutant protein. A number of
      fluorescence properties of the tethered bimane fluorophore were measured in the
      membrane-bound state of the channel domain, including fluorescence emission
      maximum, fluorescence quantum yield, fluorescence anisotropy, membrane bilayer
      penetration depth, surface accessibility, and apparent polarity. The data show
      that helix 1 is an amphipathic alpha-helix that is situated parallel to the
      membrane surface. A least squares fit of the various data sets to a harmonic
      function indicated that the periodicity and angular frequency for helix 1 are
      typical for an amphipathic alpha-helix (3.7 +/- 0.1 residues per turn and 97 +/-
      3.0 degrees, respectively) that is partially bathing into the membrane bilayer.
      Dual fluorescence quencher analysis also revealed that helix 1 is peripherally
      membrane-associated, with one face of the helix dipping into the lipid bilayer
      and the other face projecting toward the solvent. Finally, our data suggest that
      the helical boundaries of helix 1, at least at the C-terminal region, remain
      unaffected upon binding to the surface of the membrane in support of a toroidal
      pore model for this colicin.

PMID- 16299382
TI  - Inhibition of EGFR signaling in human prostate cancer PC-3 cells by combination
      treatment with beta-phenylethyl isothiocyanate and curcumin.
AB  - Many naturally occurring compounds, including beta-phenylethyl isothiocyanate
      (PEITC) and curcumin, exhibit significant anti-cancer chemopreventive effects. In
      this study, we investigated the combined effects of PEITC and curcumin in PC-3
      human prostate cancer cells and in PC-3 cells that were stably transfected with
      an NF-kappaB luciferase plasmid (PC-3 C4). We found an additive effect of PEITC
      and curcumin for the induction of apoptosis. To elucidate the potential
      mechanisms of this effect, we studied several critical cellular signaling
      pathways, including the critical NF-kappaB cell survival signal that is hyper
      activated in PC-3 cells and many other cancers. PEITC and curcumin additively
      inhibited NF-kappaB luciferase activity. Furthermore, the combined treatment
      significantly increased the activity of poly(ADP-Ribose) polymerase and cleavage
      of caspase-3 in correlation with apoptotic cell death. Studying upstream
      signaling events, we found that the phosphorylations of IkappaBalpha and Akt
      (Ser473, Thr308) were significantly attenuated by the combination of PEITC and
      curcumin. As these events can be downstream of the activation of epidermal growth
      factor receptor (EGFR), we pretreated PC-3 cells with PEITC and curcumin and then
      stimulated them with EGF. EGFR phosphorylations (Y845 and Y1068) were
      dramatically suppressed by PEITC or curcumin, and more so by the combination.
      Importantly, the degree of Akt and PI3K phosphorylations induced by EGF were also
      significantly suppressed. We conclude that the simultaneous targeting of EGFR,
      Akt and NF-kappaB signaling pathways by PEITC and curcumin could be the molecular
      targets by which PEITC and curcumin exert their additive inhibitory effects on
      cell proliferation and ultimately lead to programmed cell death of tumor cells.

PMID- 16299379
TI  - Smad6 interacts with Runx2 and mediates Smad ubiquitin regulatory factor 1
      induced Runx2 degradation.
AB  - Runx2 is a bone-specific transcription factor that plays a critical role in bone
      development, postnatal bone formation, and chondrocyte maturation. The protein
      levels of Runx2 are regulated by the ubiquitin-proteasome pathway. In previous
      studies we discovered that E3 ubiquitin ligase Smad ubiquitin regulatory factor 1
      (Smurf1) induces Runx2 degradation in a ubiquitin-proteasome-dependent manner,
      and Smurf1 plays an important role in osteoblast function and bone formation. In
      the present studies we investigated the molecular mechanism of Smurf1-induced
      Runx2 degradation. Smurf1 interacts with the PY motif of substrate proteins, and
      a PY motif has been identified in the C terminus of the Runx2 protein. To
      determine whether Smurf1 induces Runx2 degradation through the interaction with
      the PY motif of Runx2, we created a mutant Runx2 with a PY motif deletion and
      found that Smurf1 retained some of its ability to induce the degradation of the
      mutant Runx2, suggesting that Smurf1 could induce Runx2 degradation through an
      indirect mechanism. Smurf1 has been shown to interact with Smads 1, 5, 6, and 7,
      and Smads 1 and 5 also interact with Runx2. In the present studies we found that
      Smads 1 and 5 had no effect on Smurf1-induced Runx2 degradation. Although Smads 6
      and 7 bind Smurf1, it is not known if Smads 6 or 7 interacts with Runx2 and
      mediate Runx2 degradation. We performed immunoprecipitation assays and found that
      Smad6 but not Smad7 interacts with Runx2. Smad6 enhances Smurf1-induced Runx2
      degradation in an ubiquitin-proteasome-dependent manner. These results
      demonstrate that in addition to its interaction with the PY motif of Runx2,
      Smurf1 induces Runx2 degradation in a Smad6-dependent manner. Smurf1-induced
      Runx2 degradation serves as a negative regulatory mechanism for the BMP-Smad
      Runx2 signaling pathway.

PMID- 16299383
TI  - Neurotensin receptor 1 gene activation by the Tcf/beta-catenin pathway is an
      early event in human colonic adenomas.
AB  - Alterations in the Wnt/APC (adenomatous polyposis coli) signalling pathway,
      resulting in beta-catenin/T cell factor (Tcf)-dependent transcriptional gene
      activation, are frequently detected in familial and sporadic colon cancers. The
      neuropeptide neurotensin (NT) is widely distributed in the gastrointestinal
      tract. Its proliferative and survival effects are mediated by a G-protein coupled
      receptor, the NT1 receptor. NT1 receptor is not expressed in normal colon
      epithelial cells, but is over expressed in a number of cancer cells and tissues
      suggesting a link to the outgrowth of human colon cancer. Our results demonstrate
      that the upregulation of NT1 receptor occurring in colon cancer is the result of
      Wnt/APC signalling pathway activation. We first established the functionality of
      the Tcf response element within the NT1 receptor promoter. Consequently, we
      observed the activation of NT1 receptor gene by agents causing beta-catenin
      cytosolic accumulation, as well as a strong decline of endogenous receptor when
      wt-APC was restored. At the cellular level, the re-establishment of wt-APC
      phenotype resulted in the impaired functionality of NT1 receptor, like the
      breakdown in NT-induced intracellular calcium mobilization and the loss of NT pro
      invasive effect. We corroborated the Wnt/APC signalling pathway on the NT1
      receptor promoter activation with human colon carcinogenesis, and showed that NT1
      receptor gene activation was perfectly correlated with nuclear or cytoplasmic
      beta-catenin localization while NT1 receptor was absent when beta-catenin was
      localized at the cell-cell junction in early adenomas of patients with familial
      adenomatous polyposis, hereditary non-polyposis colorectal cancer and loss of
      heterozygosity tumours. In this report we establish a novel link in vitro between
      the Tcf/beta-catenin pathway and NT1 receptor promoter activation.

PMID- 16299384
TI  - Pleiotropic costs of niche expansion in the RNA bacteriophage phi 6.
AB  - Natural and experimental systems have failed to universally demonstrate a trade
      off between generalism and specialism. When a trade-off does occur it is
      difficult to attribute its cause to antagonistic pleiotropy without dissecting
      the genetic basis of adaptation, and few previous experiments provide these
      genetic data. Here we investigate the evolution of expanded host range
      (generalism) in the RNA virus phi6, an experimental model system allowing
      adaptive mutations to be readily identified. We isolated 10 spontaneous host
      range mutants on each of three novel Pseudomonas hosts and determined whether
      these mutations imposed fitness costs on the standard laboratory host. Sequencing
      revealed that each mutant had one of nine nonsynonymous mutations in the phi6
      gene P3, important in host attachment. Seven of these nine mutations were costly
      on the original host, confirming the existence of antagonistic pleiotropy. In
      addition to this genetically imposed cost, we identified an epigenetic cost of
      generalism that occurs when phage transition between host types. Our results
      confirm the existence in phi6 of two costs of generalism, genetic and
      environmental, but they also indicate that the cost is not always large. The
      possibility for cost-free niche expansion implies that varied ecological
      conditions may favor host shifts in RNA viruses.

PMID- 16299385
TI  - Relaxation of selection with equalization of parental contributions in
      conservation programs: an experimental test with Drosophila melanogaster.
AB  - Equalization of parental contributions is one of the most simple and widely
      recognized methods to maintain genetic diversity in conservation programs, as it
      halves the rate of increase in inbreeding and genetic drift. It has, however, the
      negative side effect of implying a reduced intensity of natural selection so that
      deleterious genes are less efficiently removed from the population with possible
      negative consequences on the reproductive capacity of the individuals.
      Theoretical results suggest that the lower fitness resulting from equalization of
      family sizes relative to that for free contribution schemes is expected to be
      substantial only for relatively large population sizes and after many
      generations. We present a long-term experiment with Drosophila melanogaster,
      comparing the fitness performance of lines maintained with equalization of
      contributions (EC) and others maintained with no management (NM), allowing for
      free matings and contributions from parents. Two (five) replicates of size N =
      100 (20) individuals of each type of line were maintained for 38 generations. As
      expected, EC lines retained higher gene diversity and allelic richness for four
      microsatellite markers and a higher heritability for sternopleural bristle
      number. Measures of life-history traits, such as egg-to-adult viability, mating
      success, and global fitness declined with generations, but no significant
      differences were observed between EC and NM lines. Our results, therefore,
      provide no evidence to suggest that equalization of family sizes entails a
      disadvantage on the reproductive capacity of conserved populations in comparison
      with no management procedures, even after long periods of captivity.

PMID- 16299387
TI  - Genetic addiction: selfish gene's strategy for symbiosis in the genome.
AB  - The evolution and maintenance of the phenomenon of postsegregational host killing
      or genetic addiction are paradoxical. In this phenomenon, a gene complex, once
      established in a genome, programs death of a host cell that has eliminated it.
      The intact form of the gene complex would survive in other members of the host
      population. It is controversial as to why these genetic elements are maintained,
      due to the lethal effects of host killing, or perhaps some other properties are
      beneficial to the host. We analyzed their population dynamics by analytical
      methods and computer simulations. Genetic addiction turned out to be advantageous
      to the gene complex in the presence of a competitor genetic element. The
      advantage is, however, limited in a population without spatial structure, such as
      that in a well-mixed liquid culture. In contrast, in a structured habitat, such
      as the surface of a solid medium, the addiction gene complex can increase in
      frequency, irrespective of its initial density. Our demonstration that genomes
      can evolve through acquisition of addiction genes has implications for the
      general question of how a genome can evolve as a community of potentially selfish
      genes.

PMID- 16299386
TI  - Transposon insertions of magellan-4 that impair social gliding motility in
      Myxococcus xanthus.
AB  - Myxococcus xanthus has two different mechanisms of motility, adventurous (A)
      motility, which permits individual cells to glide over solid surfaces, and social
      (S) motility, which permits groups of cells to glide. To identify the genes
      involved in S-gliding motility, we mutagenized a delta aglU (A-) strain with the
      defective transposon, magellan-4, and screened for S- mutants that form nonmotile
      colonies. Sequence analysis of the sites of the magellan-4 insertions in these
      mutants and the alignment of these sites with the M. xanthus genome sequence show
      that two-thirds of these insertions lie within 27 of the 37 nonessential genes
      known to be required for social motility, including those necessary for the
      biogenesis of type IV pili, exopolysaccharide, and lipopolysaccharide. The
      remaining insertions also identify 31 new, nonessential genes predicted to encode
      both structural and regulatory determinants of S motility. These include three
      tetratricopeptide repeat proteins, several regulators of transcription that may
      control the expression of genes involved in pilus extension and retraction, and
      additional enzymes involved in polysaccharide metabolism. Three insertions that
      abolish S motility lie within genes predicted to encode glycolytic enzymes,
      suggesting that the signal for pilus retraction may be a simple product of
      exopolysaccharide catabolism.

PMID- 16299388
TI  - Relative influences of crossing over and gene conversion on the pattern of
      linkage disequilibrium in Arabidopsis thaliana.
AB  - In this article we infer the rates of gene conversion and crossing over in
      Arabidopsis thaliana from population genetic data. Our data set is a genomewide
      survey consisting of 1347 fragments of length 600 bp sequenced in 96 accessions.
      It has several orders of magnitude more markers than any previous nonhuman study.
      This allows for more accurate inference as well as a detailed comparison between
      theoretical expectations and observations. Our methodology is specifically set to
      account for deviations such as recurrent mutations or a skewed frequency
      spectrum. We found that even if some components of the model clearly do not fit,
      the pattern of LD conforms to theoretical expectations quite well. The ratio of
      gene conversion to crossing over is estimated to be around one. We also find
      evidence for fine-scale variations of the crossing-over rate.

PMID- 16299389
TI  - The maize aberrant pollen transmission 1 gene is a SABRE/KIP homolog required for
      pollen tube growth.
AB  - Maize (Zea mays) pollen tubes grow in the styles at a rate of >1 microm/sec. We
      describe here a gene required to attain that striking rate. The aberrant pollen
      transmission 1 (apt1) gene of maize was identified by an Ac-tagged mutation that
      displayed a severe pollen transmission deficit in heterozygotes. Rare apt1
      homozygotes can be recovered, aided by phenotypic selection for Ac homozygotes.
      Half of the pollen in heterozygotes and most of the pollen in homozygotes
      germinate short and twisted pollen tubes. The apt1 gene is 26 kb long, makes an
      8.6-kb pollen-specific transcript spliced from 22 exons, and encodes a protein of
      2607 amino acids. The APT1 protein is homologous to SABRE and KIP, Arabidopsis
      proteins of unknown function involved in the elongation of root cortex cells and
      pollen tubes, respectively. Subcellular localization analysis demonstrates that
      APT1 colocalizes with a Golgi protein marker in growing tobacco pollen tubes. We
      hypothesize that the APT1 protein is involved in membrane trafficking and is
      required for the high secretory demands of tip growth in pollen tubes. The apt1
      m1(Ac) mutable allele is an excellent tool for selecting Ac transpositions
      because of the strong negative selection pressure operating against the parental
      Ac site.

PMID- 16299390
TI  - Differential usage of alternative pathways of double-strand break repair in
      Drosophila.
AB  - Double-strand DNA breaks can be repaired by any of several alternative mechanisms
      that differ greatly in the nature of the final repaired products. We used a
      reporter construct, designated "Repair reporter 3" (Rr3), to measure the relative
      usage of these pathways in Drosophila germ cells. The method works by creating a
      double-strand break at a specific location such that expression of the red
      fluorescent protein, DsRed, in the next generation can be used to infer the
      frequency at which each pathway was used. A key feature of this approach is that
      most data come from phenotypic scoring, thus allowing large sample sizes and
      considerable precision in measurements. Specifically, we measured the proportion
      of breaks repaired by (1) conversion repair, (2) nonhomologous end joining
      (NHEJ), or (3) single-strand annealing (SSA). For conversion repair, the
      frequency of mitotic crossing over in the germ line indicates the relative
      prevalence of repair by double Holliday junction (DHJ) formation vs. the
      synthesis-dependent strand annealing (SDSA) pathway. We used this method to show
      that breaks occurring early in germ-line development were much more frequently
      repaired via single-strand annealing and much less likely to be repaired by end
      joining compared with identical breaks occurring later in development. Conversion
      repair was relatively rare when breaks were made either very early or very late
      in development, but was much more frequent in between. Significantly, the changes
      in relative usage occurred in a compensatory fashion, such that an increase in
      one pathway was accompanied by decreases in others. This negative correlation is
      interpreted to mean that the pathways for double-strand break repair compete with
      each other to handle a given breakage event.

PMID- 16299391
TI  - High mobility group proteins HMGD and HMGZ interact genetically with the Brahma
      chromatin remodeling complex in Drosophila.
AB  - Many pleiotropic roles have been ascribed to small abundant HMG-Box (HMGB)
      proteins in higher eukaryotes but their precise function has remained enigmatic.
      To investigate their function genetically we have generated a defined deficiency
      uncovering the functionally redundant genes encoding HMGD and HMGZ, the
      Drosophila counterparts of HMGB1-3 in mammals. The resulting mutant is a strong
      hypomorphic allele of HmgD/Z. Surprisingly this allele is viable and exhibits
      only minor morphological defects even when homozygous. However, this allele
      interacts strongly with mutants of the Brahma chromatin remodeling complex, while
      no interaction was observed with mutant alleles of other remodeling complexes. We
      also observe genetic interactions between the HmgD/Z deficiency and some, but not
      all, known Brahma targets. These include the homeotic genes Sex combs reduced and
      Antennapedia, as well as the gene encoding the cell-signaling protein Rhomboid.
      In contrast to more general structural roles previously suggested for these
      proteins, we infer that a major function of the abundant HMGB proteins in
      Drosophila is to participate in Brahma-dependent chromatin remodeling at a
      specific subset of Brahma-dependent promoters.

PMID- 16299392
TI  - Assessing the fidelity of ancient DNA sequences amplified from nuclear genes.
AB  - To date, the field of ancient DNA has relied almost exclusively on mitochondrial
      DNA (mtDNA) sequences. However, a number of recent studies have reported the
      successful recovery of ancient nuclear DNA (nuDNA) sequences, thereby allowing
      the characterization of genetic loci directly involved in phenotypic traits of
      extinct taxa. It is well documented that postmortem damage in ancient mtDNA can
      lead to the generation of artifactual sequences. However, as yet no one has
      thoroughly investigated the damage spectrum in ancient nuDNA. By comparing clone
      sequences from 23 fossil specimens, recovered from environments ranging from
      permafrost to desert, we demonstrate the presence of miscoding lesion damage in
      both the mtDNA and nuDNA, resulting in insertion of erroneous bases during
      amplification. Interestingly, no significant differences in the frequency of
      miscoding lesion damage are recorded between mtDNA and nuDNA despite great
      differences in cellular copy numbers. For both mtDNA and nuDNA, we find
      significant positive correlations between total sequence heterogeneity and the
      rates of type 1 transitions (adenine --> guanine and thymine --> cytosine) and
      type 2 transitions (cytosine --> thymine and guanine --> adenine), respectively.
      Type 2 transitions are by far the most dominant and increase relative to those of
      type 1 with damage load. The results suggest that the deamination of cytosine
      (and 5-methyl cytosine) to uracil (and thymine) is the main cause of miscoding
      lesions in both ancient mtDNA and nuDNA sequences. We argue that the problems
      presented by postmortem damage, as well as problems with contamination from
      exogenous sources of conserved nuclear genes, allelic variation, and the reliance
      on single nucleotide polymorphisms, call for great caution in studies relying on
      ancient nuDNA sequences.

PMID- 16299393
TI  - Estimating the "effective number of codons": the Wright way of determining codon
      homozygosity leads to superior estimates.
AB  - In 1990, Frank Wright introduced a method for measuring synonymous codon usage
      bias in a gene by estimation of the "effective number of codons," N(c). Several
      attempts have been made recently to improve Wright's estimate of N(c), but the
      methods that work in cases where a gene encodes a protein not containing all
      amino acids with degenerate codons have not been tested against each other. In
      this article I derive five new estimators of N(c) and test them together with the
      two published estimators, using resampling under rigorous testing conditions.
      Estimation of codon homozygosity, F, turns out to be a key to the estimation of
      N(c). F can be estimated in two closely related ways, corresponding to sampling
      with or without replacement, the latter being what Wright used. The N(c) methods
      that are based on sampling without replacement showed much better accuracy at
      short gene lengths than those based on sampling with replacement, indicating that
      Wright's homozygosity method is superior. Surprisingly, the methods based on
      sampling with replacement displayed a superior correlation with mRNA levels in
      Escherichia coli.

PMID- 16299395
TI  - Primate chaperones Hsc70 (constitutive) and Hsp70 (induced) differ functionally
      in supporting growth and prion propagation in Saccharomyces cerevisiae.
AB  - Hsp70's are highly conserved essential protein chaperones that assist protein
      folding and prevent protein aggregation. They have modular structures consisting
      of ATPase, substrate-binding, and C-terminal domains. Substrate binding and
      release is regulated by ATP hydrolysis and nucleotide exchange, which in turn are
      regulated by cochaperones. Eukaryotes have constitutive (Hsc70) and stress
      inducible (iHsp70) isoforms, but their functions have not been systematically
      compared. Using a yeast system to evaluate heterologous Hsp70's we find that
      primate Hsc70 supported growth but iHsp70 did not. Plant Hsc70 and iHsp70
      counterparts behaved similarly, implying evolutionary conservation of this
      distinction. Swapping yeast and primate Hsp70 domains showed that (i) the Hsc70
      iHsp70 distinction resided in the ATPase domain, (ii) substrate-binding domains
      of Hsp70's within and across species functioned similarly regarding growth, (iii)
      C-terminal domain function was important for growth, and (iv) Hsp70 functions
      important for cell growth and prion propagation were separable. Enzymatic
      analysis uncovered a correlation between substrate affinity and prion phenotype
      and showed that ATPase and protein-folding activities were generally similar. Our
      data support a view that intrinsic activities of Hsp70 isoforms are comparable,
      and functional differences in vivo lie mainly in complex interactions of Hsp70
      with cochaperones.

PMID- 16299394
TI  - eae36, a locus on mouse chromosome 4, controls susceptibility to experimental
      allergic encephalomyelitis in older mice and mice immunized in the winter.
AB  - Genetic factors are believed to contribute to multiple sclerosis (MS)
      susceptibility; however, strong evidence implicating intrinsic and environmental
      factors in the etiopathogenesis of MS also exists. Susceptibility to experimental
      allergic encephalomyelitis (EAE), the principal animal model of MS, is also
      influenced by nongenetic factors, including age and season at immunization. This
      suggests that age- and season-by-gene interactions exist and that different
      susceptibility loci may influence disease as a function of the two parameters. In
      this study, linkage analysis based on genome exclusion mapping was carried out
      using age and season at immunization restricted cohorts of (B10.S x SJL/J) F2
      intercross mice in an effort to identify such linkages. Significant linkage of
      EAE to eae4 and eae5 was detected with 6- to 12-week-old and summer cohorts. In
      contrast, significant linkage of EAE to eae4 and eae5 was not detected with the
      >12-week-old and winter/spring populations. Rather, significant linkage to
      D4Mit203 at 128.50 Mb on chromosome 4 was detected with animals that were >12
      weeks old at the time of immunization or were immunized in the winter. This
      previously unidentified locus has been designated eae36. These results support
      the existence of age- and season-by-gene-specific interactions in the genetic
      control of susceptibility to autoimmune inflammatory disease of the central
      nervous system and suggest that late-onset MS may be immunogenetically distinct.

PMID- 16299396
TI  - Approximate Bayesian inference reveals evidence for a recent, severe bottleneck
      in a Netherlands population of Drosophila melanogaster.
AB  - Genome-wide nucleotide variation in non-African populations of Drosophila
      melanogaster is a subset of variation found in East sub-Saharan African
      populations, suggesting a bottleneck in the history of the former. We implement
      an approximate Bayesian approach to infer the timing, duration, and severity of
      this putative bottleneck and ask whether this inferred model is sufficient to
      account for patterns of variability observed at 115 loci scattered across the X
      chromosome. We estimate a recent bottleneck 0.006N(e) generations ago, somewhat
      further in the past than suggested by biogeographical evidence. Using various
      proposed statistical tests, we find that this bottleneck model is able to predict
      the majority of observed features of diversity and linkage disequilibrium in the
      data. Thus, while precise estimates of bottleneck parameters (like inferences of
      selection) are sensitive to model assumptions, our results imply that it may be
      unnecessary to invoke frequent selective sweeps associated with the dispersal of
      D. melanogaster from Africa to explain patterns of variability in non-African
      populations.

PMID- 16299398
TI  - Effects of transdermal estrogen on levels of lipids, lipase activity, and
      inflammatory markers in men with prostate cancer.
AB  - Androgen deprivation therapy (ADT) for prostate cancer is now used in earlier
      disease stages and as adjuvant treatment. Recognizing and reducing the toxicity
      of this therapy, including worsened lipid levels and cardiovascular disease (CVD)
      risks, has become an important clinical concern. Oral estrogen therapy induces
      hypogonadism and mitigates many side effects of ADT, but has a high thrombosis
      risk. Transdermal estrogen therapy (TDE) has a lower thrombosis risk than oral
      estrogen and may improve CVD risk compared with ADT. This prospective pilot study
      of 18 men with androgen-independent prostate cancer receiving ADT measured
      effects of TDE on lipid and inflammatory CVD risk factors before and after 8
      weeks of TDE (estradiol 0.6 mg/day). During treatment, estradiol levels rose 17
      fold; total cholesterol, LDL cholesterol, and apolipoprotein B levels decreased.
      HDL2 cholesterol increased, with no changes in triglyceride or VLDL cholesterol
      levels. Dense LDL cholesterol decreased and LDL buoyancy increased in association
      with a decrease in HL activity. Highly sensitive C-reactive protein levels and
      other inflammatory markers did not worsen. Compared with ADT, short-term TDE
      therapy of prostate cancer improves lipid levels without deterioration of CVD
      associated inflammatory markers and may, on longer-term follow-up, improve CVD
      and mortality rates.

PMID- 16299397
TI  - Estimating selection on nonsynonymous mutations.
AB  - The distribution of mutational effects on fitness is of fundamental importance
      for many aspects of evolution. We develop two methods for characterizing the
      fitness effects of deleterious, nonsynonymous mutations, using polymorphism data
      from two related species. These methods also provide estimates of the proportion
      of amino acid substitutions that are selectively favorable, when combined with
      data on between-species sequence divergence. The methods are applicable to
      species with different effective population sizes, but that share the same
      distribution of mutational effects. The first, simpler, method assumes that
      diversity for all nonneutral mutations is given by the value under mutation
      selection balance, while the second method allows for stronger effects of genetic
      drift and yields estimates of the parameters of the probability distribution of
      mutational effects. We apply these methods to data on populations of Drosophila
      miranda and D. pseudoobscura and find evidence for the presence of deleterious
      nonsynonymous mutations, mostly with small heterozygous selection coefficients (a
      mean of the order of 10(-5) for segregating variants). A leptokurtic gamma
      distribution of mutational effects with a shape parameter between 0.1 and 1 can
      explain observed diversities, in the absence of a separate class of completely
      neutral nonsynonymous mutations. We also describe a simple approximate method for
      estimating the harmonic mean selection coefficient from diversity data on a
      single species.

PMID- 16299399
TI  - Alterations of the BRAF gene in thyroid tumors.
AB  - BRAF belongs to the RAF family of protein kinases that are important components
      of the MAPK signaling pathway mediating cell growth, differentiation and
      survival. Activating point mutation of the BRAF gene resulting in V600E
      (previously designated as V599E) is a common event in thyroid papillary
      carcinoma, being found in approx 40% of this tumor. It has strong association
      with classical papillary carcinoma and tall cell and possibly Warthin-like
      variants. This mutation also occurs in thyroid poorly differentiated and
      anaplastic carcinomas, usually those containing areas of papillary carcinoma.
      Alterations in the BRAF gene do not overlap with RAS mutations and RET/PTC
      rearrangement, indicating that activation of one of the effectors of the MAPK
      pathway is sufficient for papillary thyroid carcinogenesis. Recently, another
      mechanism of BRAF activation has been identified, which involves chromosome 7q
      inversion that results in the AKAP9-BRAF fusion. It is rare in sporadic papillary
      carcinomas and is more common in tumors associated with radiation exposure. Yet
      another mechanism of BRAF activation may involve copy number gain, which is seen
      in a significant portion of thyroid follicular tumors of both conventional and
      oncocytic (Hurthle cell) types.

PMID- 16299401
TI  - Double adenomas of the pituitary: transcription factors Pit-1, T-pit, and SF-1
      identify cytogenesis and differentiation.
AB  - The diagnosis of double adenomas of the pituitary can be very complex and is
      usually suspected on histological assessment of a specimen and confirmed by
      immunohistochemical and ultrastructural studies. The most commonly applied
      technique is currently immunohistochemical staining to localize the six pituitary
      hormones. Application of this technique may fail to identify double adenomas when
      hormone immunoreactivity is weak or absent in one or both cell populations. We
      examined specimens from eight patients diagnosed with double adenomas over a 15
      yr period. We tested the ability to detect the difference in the two adenomas in
      each case using three immunostains for the pituitary transcription factors Pit-1,
      T-pit, and SF-1. We conclude that immunohistochemical localization of the
      transcription factors Pit-1, T-pit, and SF-1 accurately detects and classifies
      the distinct cytodifferentiation of double adenomas of the pituitary.

PMID- 16299402
TI  - The pituitary in Turner syndrome.
AB  - Although Turner syndrome is not uncommon, studies of the pituitary in this
      condition are few. We undertook a histochemical and immunohistochemical study of
      four cases. As expected, "gonadal failure cells" were seen, but without
      recognizable gonadotroph hyperplasia. No gonadotroph adenomas were encountered.
      Instead, three silent corticotroph microadenomas were seen; their etiology
      remains unexplained. The question of whether the simultaneous occurrence of
      Turner syndrome and silent corticotroph adenoma is causal or incidental cannot be
      answered on the basis of the study of our material. Because these two diseases
      are rare, an etiologic association has to be considered. For example, it is
      possible that (a) protracted stimulation of gonadotrophs leads to
      transdifferentiation to corticotrophs, a hypothesis supported by the fact that
      normal and neoplastic gonadotrophs can contain ACTH and that some corticotroph
      adenomas produce LH and/or alpha subunit, (b) corticotrophs develop gonadotropin
      releasing hormone (GnRH) receptors and undergo neoplastic transformation when
      exposed to continuous elevation of GnRH, FSH, and/or LH levels, and (c) the
      genetic defect in Turner syndrome promotes the formation of corticotroph
      adenomas.

PMID- 16299400
TI  - Chromogranin A transcription and gene expression in Folliculostellate (TtT/GF)
      cells inhibit cell growth.
AB  - Folliculostellate (FS) cells are present in the anterior pituitary and have
      important regulatory functions including controlling hormone release from other
      anterior pituitary cells. FS cells do not usually express neuroendocrine genes
      such as chromogranin A (CgA). We analyzed transcriptional regulation and gene
      expression in the TtT/GF FS cell line to better understand the role of FS cells
      in anterior pituitary function. After transient transfection with a human (h) CgA
      promoter sequence linked to a luciferase reporter, there was basal level of
      transcriptional activity, which was two- to fourfold less than that observed in
      the anterior pituitary neuroendocrine cell lines HP75 and GH3. The
      transcriptional activity was decreased in all cell lines when a mutant hCgA
      promoter cyclic AMP response element (CRE) was used for transfection. Sodium
      butyrate treatment increased the transcriptional activity in all cell lines, but
      remained two- to fourfold higher in the HP75 and GH3 cell lines than in the
      TtT/GF cells. Stable transfection of a plasmid expressing bovine (b) CgA in the
      TtT/GF cells led to inhibition of cell growth as measured by 3H-thymidine
      incorporation, Ki-67 labeling index, and growth curve analysis. CgA protein and
      mRNA could be readily demonstrated in the cloned cells but not in the parental
      cell line or vector control cells. When the CgA expressing cloned cells were
      injected into SCID mice, there was a decrease in the rate of tumor growth
      compared to the vector control in vivo. These results indicate that the TtT/GF FS
      cells are fibroblast-like compared to the neuroendocrine anterior pituitary
      secretory cells when analyzed by transcriptional activity with a transiently
      transfected CgA promoter. In TtT/GF cells with a stably transfected bCgA plasmid,
      CgA has a direct regulatory effect on tumor cell proliferation.

PMID- 16299403
TI  - Cytokeratin CK 7 and CK 20 expression in pituitary adenomas.
AB  - The pattern of immunohistochemical expression of cytokeratins 7 (CK 7) and 20 (CK
      20) is commonly used to assess possible primary sites of metastatic carcinomas.
      Because pituitary tumors are almost always benign, there has been little interest
      in their cytokeratin profile. However, we recently reported the use of CK 7/20
      expression to document malignant progression and metastasis of a pituitary tumor,
      indicating the potential diagnostic usefulness of the CK 7/20 profile of
      pituitary adenomas. We analyzed CK 7/20 expression in 97 pituitary adenomas
      subclassified by immunohistochemical hormone expression. In about 90% of all
      subtypes, CK 7 was either negative or reactive in only a few scattered cells.
      Corticotrophs and sparsely granulated growth hormone-positive adenomas were
      consistently CK 20 positive (and CK 7 negative) whereas all other subtypes were
      almost always CK 20 negative. This CK 20-positive, CK 7-negative profile is
      previously described consistently only in colonic adenocarcinomas. This study
      documents that subtypes of pituitary adenomas have different CK 7/20 profiles.
      Whereas this pattern is likely to have diagnostic usefulness in only rare
      adenomas, the presence of a unique CK signature in corticotrophs and sparsely
      granulated growth hormone-positive adenomas, subtypes particularly noted for
      invasive and aggressive behavior, merits further investigation.

PMID- 16299405
TI  - Angiogenesis and the growth potential of craniopharyngiomas.
AB  - The present study was performed to evaluate the role of neovascularization on the
      behavior of craniopharyngiomas as well as the contribution of endothelial cell
      proliferation and migration in the remodeling and expansion of the vascular
      network associated with angiogenesis. Fourteen primary tumors were studied, all
      of the adamantinomatous type. CD34 immunostaining, an endothelial cell marker,
      localized vessels within the connective tissue stroma. MIB-1 immunopositivity was
      apparent in the nuclei of neoplastic cells, few endothelial cells, and stromal
      elements. MIB-1 counts were higher in epithelial than connective tissue cells. A
      positive correlation was found between the number of MIB-1 immunopositive cells
      and microvessel density (MVD). Immunohistochemistry demonstrated that integrin
      alphavbeta3 expression was restricted to tumor vasculature; the tumor cells were
      immunonegative. Only 2.5% of vessels detected with CD34 were immunopositive for
      integrin alphavbeta3. At present, no therapeutic implications can be drawn from
      our observations. More studies are needed to assess whether integrin alphavbeta3
      antagonists or drugs that arrest the cell cycle of endothelial cells can inhibit
      angiogenesis in craniopharyngiomas.

PMID- 16299404
TI  - Expression of human telomerase reverse transcriptase in thyroid follicular
      neoplasms: an immunohistochemical study.
AB  - Differential diagnosis of follicular adenoma (FA) and follicular carcinoma (FC)
      of the thyroid can be difficult in the routine practice of surgical pathology
      because the diagnosis of FC is strictly defined and determined by the presence of
      capsular and/or vascular invasion by the tumor. These features may be equivocal
      in the histologic sections. On the other hand, telomerase is expressed in many
      human cancers and is thought to contribute to their immortality. Human telomerase
      reverse transcriptase (hTERT) is the major determinant of human telomerase
      activity, and its expression is suggestive of capacity for unlimited replication.
      This case-control study examined the expression of hTERT using
      immunohistochemistry in 36 thyroid FC and 36 FA from patients who were matched by
      age and sex. The aim was to investigate the value of immunohistochemical staining
      for hTERT in the differential diagnosis of follicular neoplasms. The results
      revealed 23 cases of FC and 14 cases of FA that showed high expression of hTERT,
      with moderate to strong immunoreactivity. The remaining cases showed weak or
      negative staining. The difference between FA and FC was statistically significant
      (p < 0.05). In conclusion, immunohistochemical staining for hTERT can be
      considered an ancillary marker for differential diagnosis of FA and FC.

PMID- 16299406
TI  - Expression of heterogeneous nuclear ribonucleoproteins A2 and b1 in the thyroid
      follicular cells.
AB  - Several proteins implicated in hormonogenesis of the thyroid have alternatively
      spliced isoforms. Alternative splicing of pre-mRNA is considered to be important
      to regulate the hormonal activity. Heterogeneous nuclear ribonucleoproteins
      (hnRNP) A2 and B1 are two of the abundant nuclear RNA-binding proteins involved
      in alternative splicing. We examined the expression of hnRNP A2 and B1 in the
      thyroid, paying particular attention to the relationship between their function
      and the cellular morphology. B1 was expressed more frequently in cuboidal
      follicular cells that are hormonally active than in flat follicular cells in
      normal thyroid, although A2 expression showed no significant difference in two
      cell types. In Graves' disease, the patients who had high serum levels of
      triiodothyronine and thyroxine showed significantly increased expression of B1.
      B1 expression did not differ significantly between normal thyroids and thyroid
      neoplasms, except undifferentiated (anaplastic) carcinoma. Conclusively, B1
      expression varied in relation to hormonal activity in thyroid follicular cells.
      B1 protein is a good immunohistological marker to detect hormonal activity of
      follicular cells, and may provide a key to elucidate the splicing mechanisms
      involved in thyroid hormonogenesis.

PMID- 16299407
TI  - Co-localization of honeycomb golgi and ACTH granules in a giant ACTH-producing
      pituitary adenoma.
AB  - We document the co-localization of honeycomb golgi and ACTH-immunopositive
      granules in giant ACTH-producing pituitary adenoma cells. A 42-yr-old woman
      presented with Cushing's disease and a giant adenoma that invaded the sphenoid
      and cavernous sinus. She underwent transsphenoidal surgery followed by radiation
      therapy. Some of the adenoma cells were ACTH-positive and upon electron
      microscopic (EM) study most were found to contain sparse granules and no type-I
      filaments. In many cells the golgi complex had undergone partial or total
      vacuolar transformation that resulted in the appearance of honeycomb golgi.
      Immunohistochemical study of mirror sections of portions containing cells with
      honeycomb golgi revealed that the cells with honeycomb golgi showed ACTH
      immunopositivity. Honeycomb golgi, which was formerly considered a morphological
      marker of gonadotroph adenomas in females, has previously been identified in
      large ACTH-producing pituitary adenomas but there has been no direct evidence
      that individual cells with honeycomb golgi are cells that produce ACTH. Our
      immunohistochemical documentation of ACTH-immunoreactivity in individual adenoma
      cells containing honeycomb golgi clearly confirms that honeycomb golgi is not
      confined only to gonadotroph adenomas in females. Rather, the existence of
      honeycomb golgi in cells of other adenoma types may be due to their low hormone
      production and/or to disturbances in the regulation of the exocytotic pathway.

PMID- 16299408
TI  - Anaplastic thyroid cancer and hyperthyroidism.
AB  - We report a rare case of thyrotoxicosis in a patient with anaplastic thyroid
      cancer. A 65-yr-old male presented with a 2-d history of rapidly enlarging neck
      mass and back pain. Physical examination revealed a large, hard thyroid mass and
      resting tachycardia. He did not have any symptoms suggestive of airway
      compression at presentation. Thyroid hormone levels were consistent with a
      hyperthyroid state. CT scan of the neck and thorax showed a heterogeneous mass
      replacing the thyroid, bilateral pulmonary nodules, and a metastasis with
      pathological fracture at the level of T-8. Technetium-pertechnetate scan failed
      to show any uptake in the region of the thyroid. Fine needle aspiration of the
      thyroid revealed anaplastic thyroid cancer. The patient was started on steroids
      and radiation therapy of his spine lesion. Brief surgical exploration of the
      thyroid revealed extensive local infiltration of adjacent neck tissues and marked
      tumor necrosis. Immunohistochemical stains of the tumor were positive for p53,
      thyroglobulin, and thyroid transcription factor-1. The tumor had an extremely
      aggressive course and the patient died of asphyxiation from severe airway
      compromise 11 d after his initial presentation.

PMID- 16299409
TI  - Concerning the article by s. Belda et Al.: screening for retinopathy of
      prematurity: is it painful?

PMID- 16299411
TI  - Exaggerated TSH responses to TRH in patients with goiter and 'normal' basal TSH
      levels.
AB  - BACKGROUND/AIM: The availability of sensitive thyrotropin (TSH) assays decreased
      the diagnostic value of thyrotropin-releasing hormone stimulation tests (TRH-ST)
      in subclinical hypothyroidism. In this study we aimed to evaluate the relation
      between basal and stimulated serum TSH levels on TRH-ST and to determine the
      prevalence of patients with normal basal serum TSH and exaggerated TSH responses.
      METHODS: 179 patients (117 girls, 123 pubertal) with a median age of 12 (2.7
      21.4) years who presented with goiter were enrolled and evaluated for their
      pubertal stage, height, thyroid autoimmunity, ultrasonography, thyroid function,
      and TRH-ST. Serum TSH concentrations were determined by sensitive assays. At TRH
      ST, a peak serum TSH level >25 mIU/l was considered as an exaggerated response.
      RESULTS: 30 (17%) patients had an exaggerated TSH response. In patients with
      serum TSH levels between 2 and 4.68 mIU/l (upper half the normal range), an
      exaggerated TSH response was observed in 19.5%. A positive correlation between
      basal and TRH-stimulated TSH levels was determined (r = 0.536, p < 0.01). In
      patients with an exaggerated TSH response, 23 had normal (discordant) and 7 had
      high basal TSH levels (concordant). The mean basal serum TSH level was lower in
      the discordant group compared to the concordant group (p < 0.01). CONCLUSION:
      Basal serum TSH levels might not be sufficient for diagnosing subclinical
      hypothyroidism. Stimulated TSH levels on TRH-ST are valuable, especially when
      serum TSH concentrations are in the upper half of the normal range.

PMID- 16299412
TI  - Effects of cyclooxygenase-1 and -2 inhibition on gastric acid secretion and
      cardiovascular functions in rats.
AB  - The discovery of a second isoform of cyclooxygenase has led to a re-evaluation of
      the mechanisms underlying the adverse effects of nonsteroidal anti-inflammatory
      drugs, focusing in particular on the gastrointestinal system. We investigated the
      involvement of cyclooxygenase-1 and -2 in the regulation of gastric acid
      secretion and cardiovascular functions in anesthetized rats, after acute
      intravenous administration of the selective cyclooxygenase-1 inhibitor SC-560,
      the selective cyclooxygenase-2 inhibitor celecoxib and the nonselective inhibitor
      indomethacin. Indomethacin, celecoxib and SC-560 did not significantly modify
      basal acid secretion. Indomethacin and celecoxib were also ineffective on the
      acid secretion stimulated by pentagastrin; by contrast, SC-560 significantly
      enhanced the acid secretion stimulated by pentagastrin, electrical vagal
      stimulation or histamine. The stimulatory effects of SC-560 were prevented by
      cervical vagotomy, atropine and famotidine. Indomethacin caused either no change,
      increasing or decreasing effects on mean arterial pressure and heart rate. By
      contrast, SC-560 was unable to change cardiovascular parameters at 5 mg/kg, while
      inducing a marked bradycardia at 10 mg/kg. Celecoxib was ineffective. Our
      findings indicate that cyclooxygenase-1-derived prostaglandins are involved in
      the regulation of stimulated acid secretion and of basal heart rate; the role of
      prostaglandins in the acute control of systemic blood pressure under resting
      conditions seems to be negligible.

PMID- 16299413
TI  - Childhood inattention and hyperactivity symptoms self-reported by adults with
      Asperger syndrome.
AB  - BACKGROUND: Increasing public awareness of the adult manifestations of
      developmental neuropsychiatric disorders, like Asperger syndrome and attention
      deficit hyperactivity disorder (ADHD), has provoked an increasing number of
      persons to seek assessment for the first time in adulthood. As these disorders
      have their origin in childhood, instruments for retrospective evaluation of
      childhood behavior are needed. SAMPLING AND METHODS: In this preliminary study,
      20 adults with Asperger syndrome filled in the Wender-Utah Rating Scale for ADHD
      to describe retrospectively their childhood behavior. RESULTS: Fourteen out of 20
      adults with Asperger syndrome self-rated above the cut-off limit for ADHD. The
      median total score was also higher than that reported in normal populations in
      previous studies. When compared with 10 controls, patients with Asperger syndrome
      scored higher in almost all individual items. CONCLUSIONS: A high score on the
      Wender-Utah rating Scale for ADHD in this patient group might be a sign of true
      comorbidity with ADHD, an indication of overlapping features typical of both
      disorders, or a result of other psychiatric comorbidity originating already in
      childhood. Moreover, there are no data about the proper cut-off limit for ADHD in
      these subjects. Therefore, one should be cautious when applying this scale beyond
      its original context of comparison between adults with ADHD, unipolar depression
      and healthy controls.

PMID- 16299414
TI  - Influence of nasal resistance on initial acceptance of continuous positive airway
      pressure in treatment for obstructive sleep apnea syndrome.
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) is considered as the
      standard therapy for obstructive sleep apnea syndrome (OSAS), but some patients
      with OSAS are unable to accept CPAP due to nasal obstruction and poor nasal
      airflow. OBJECTIVES: We assessed the influence of nasal resistance before
      beginning CPAP treatment on the initial acceptance of CPAP in OSAS patients.
      METHODS: The study subjects comprised 77 patients (74 males, 3 females) with
      primary OSAS, all of whom received CPAP treatment with nasal masks. Before
      trials, all subjects underwent overnight polysomnography, and nasal resistance
      was measured with active anterior rhinomanometry in the seated position on the
      first day of CPAP trial. RESULTS: The CPAP treatment was accepted by 56 patients
      after the initial trials with overnight polysomnography. Body mass index, the
      number of apnea/hypopnea episodes per hour (apnea/hypopnea index; AHI), and the
      number of episodes per hour with an oxygen desaturation of >3% (oxygen
      desaturation index) were significantly higher (p<0.01) and nasal resistance was
      lower (p=0.003) in patients who accepted CPAP than in those who did not. Logistic
      regression analysis, with patient age, body mass index, Epworth sleepiness scale
      score, AHI, oxygen desaturation index, and nasal resistance before CPAP treatment
      as explanatory variables, showed that nasal resistance (OR+0.1 Pa/cm3/s: 1.48;
      p=0.002) and AHI (OR+1 event/h: 0.93; p=0.003) were significant factors for CPAP
      non-acceptance. CONCLUSIONS: Nasal resistance before the beginning of CPAP
      treatment has a significant effect on the acceptance of CPAP in OSAS patients,
      and hence, could be a predictive parameter for the initial acceptance of CPAP.

PMID- 16299415
TI  - Effects of fasting and refeeding on serum leptin, adiponectin and free fatty acid
      concentrations in young and old male rats.
AB  - BACKGROUND: Regulatory mechanisms of metabolic homeostasis undergo important
      alterations during ageing. The age-related changes become often evident only
      during stimulation of basic functions that occurs, e.g. during fasting and
      refeeding which represent natural challenge to energy metabolism. OBJECTIVE: To
      determine the effect of short-term fasting and subsequent refeeding on serum
      levels of key hormones and metabolites in young adult 5- and 24-month-old male
      Wistar rats. METHODS: Control rats were fed ad libitum. Animals were fasted for
      48 h or fasted and refed for 24 h. Metabolite serum concentrations were measured
      by standard methods. Leptin and insulin were determined by rat-specific RIA, and
      adiponectin serum levels by mouse/rat-specific ELISA. RESULTS: (1) Control serum
      levels of key metabolites and hormones were similar in both age groups except for
      increased triglycerides (TG) in old fed rats. (2) Fasting caused a significant
      decrease of leptin, insulin, glucose, and TG serum levels in both age groups, and
      an increase of free fatty acids (FFA) concentration, however, only in young
      animals. (3) Upon refeeding serum glucose, TG and insulin reversed to control
      levels in both age groups, however, FFA concentration decreased to control values
      only in young rats. (4) In contrast to young animals, refeeding of old rats did
      not increase serum leptin concentration to control level. (5) Neither fasting nor
      refeeding changed adiponectin serum levels in both age groups. CONCLUSION: Aging
      suppresses leptin secretion and metabolism of FFA during refeeding that follows
      short-term starvation. In old rats serum levels of FFA are refractive to the
      alterations induced by fasting/refeeding in young ones.

PMID- 16299416
TI  - Aging: functional metabolic balance among cAMP, cGMP and reactive oxygen
      intermediate generation by human granulocytes.
AB  - BACKGROUND: The nature of the aging process has been the subject of considerable
      speculation. It has been reported that in the aging process several components of
      the signal transduction pathways, including phosphoinositide, protein kinase C,
      protein kinase A and reactive oxygen intermediate (ROI) generation, are altered.
      OBJECTIVE: The aim of our study was to evaluate the functional metabolic balance
      among cAMP, cGMP and ROI generation by human neutrophils in relation to age.
      METHODS: The age-induced ROI generation was studied in healthy subjects ranging
      in age from 20 to 80 years old, divided into 6 age groups: 20-29, 30-39, 40-49,
      50-59, 60-69 and 70-80 years old. The oxidizing cellular generation was
      quantified in a luminol-dependent (ROI production) chemiluminescence assay and
      the results expressed as relative light units per minute. RESULTS: Our results
      show a differential functional metabolic balance of cAMP and cGMP in relation to
      age from 50 years on. This phenomenon is reflected by the increase in ROI
      generation by neutrophil stimulation with cGMP at all ages and a simultaneous
      lack of effect of cAMP on cGMP from 50 years old. The same results were observed
      when neutrophil reacted with endogenous contents of cGMP (levamisole, an
      inhibitor of cGMP phosphodiesterase) or cAMP (aminophylline, an inhibitor of cAMP
      phosphodiesterase). Our results show that the lack of modulation of the
      endogenous or exogenous contents of cAMP or cGMP on ROI generation altered the
      age-related functional metabolic balance. CONCLUSIONS: This altered functional
      metabolic balance in cAMP, cGMP and ROI generation of neutrophils may certainly
      have consequences on host defenses, mainly on inflammatory processes, in healthy
      subjects from 50 years old. However, the exact consequences of this phenomenon on
      the aging process remain unknown.

PMID- 16299417
TI  - Cell proliferation in the dentate gyrus of rat hippocampus is inhibited by soft
      diet feeding.
AB  - BACKGROUND: Recently it has become well accepted that neurogenesis occurs in the
      dentate gyrus of the hippocampus, a region important to memory and learning
      function in rodents and humans. Reports show that neurogenesis in the hippocampus
      is regulated by certain factors, such as exposure to an enriched environment,
      physical activity, aging and stress. The relationship between the change in the
      task of chewing as one oral environmental factor, and the mechanisms of
      hippocampal neuron generation are unclear. OBJECTIVE: We examined whether cell
      proliferation varies by chewing tasks with different food textures in the dentate
      gyrus of the rat hippocampus. METHODS: Wistar rats were divided into two groups,
      one was fed a solid diet, known as the hard-diet feeding group, and the soft-diet
      feeding group, which was fed a powder diet containing the same components as the
      solid one for 3, 7, 16 and 24 weeks. Thymidine analog 5-bromo-2'-deoxyuridine
      (BrdU) was used as a marker of cell proliferation within the dentate gyrus of the
      hippocampus and olfactory bulb. RESULTS: The results of this study indicated that
      the total number of BrdU-positive cells in the hippocampal dentate gyrus
      significantly decreased with aging and were significantly fewer in the soft-diet
      feeding group than in hard-diet feeding group in 7-, 16- and 24-week-old rats
      after the BrdU injection. The change of BrdU-positive cell expression between
      soft and hard diets in 3- and 24-week-old rats was not observed in the olfactory
      bulb. CONCLUSION: It has been suggested that cell proliferation in the dentate
      gyrus of the rat hippocampus is characteristically suppressed by soft diet
      feeding.

PMID- 16299418
TI  - The preference and importance of bathing, toileting and mouth care habits in
      older persons.
AB  - PURPOSE: The goal of this study was to describe bathing, toileting, and mouth
      care habits and preferences of older persons, as well as the importance of such
      habits. DESIGN AND METHODS: Fifty-eight community-dwelling older persons were
      administered the Self-maintenance Habits And Preferences in Elderly questionnaire
      (SHAPE) during a one-on-one interview with a research assistant. Preferences were
      described by frequency distributions and mean importance for each item was
      calculated. Gender differences in preferences were examined using chi(2)
      analyses, t tests were used to compare importance levels. RESULTS: Women reported
      spending a longer time bathing, they were more likely to have privacy while
      bathing, to use a washcloth, a regular size towel, and less likely to use a large
      towel than were men. One-third of the women reported using some type of absorbent
      undergarment, while no men did so. Mouth care was the category that received the
      highest importance ratings. Although order of importance of items was similar
      across genders, women assigned higher levels of importance to these items than
      did men. Importance ratings given to atypical habits, such as unusually long or
      more than 1 bath/day, were higher than those attributed to more usual habits.
      IMPLICATIONS: Knowledge of the range and importance of such self-care practices
      can provide information useful in the development of programs and for
      individualized care.

PMID- 16299419
TI  - Benign paroxysmal positional vertigo among elderly patients in primary health
      care.
AB  - BACKGROUND: Dizziness influences well-being in old age, and benign paroxysmal
      positional vertigo (BPPV) is a common cause. The condition is diagnosed using the
      Hallpike maneuver and treated by the particle-repositioning maneuver or
      habituation exercises. OBJECTIVE: To identify patients with BPPV among a variety
      of diagnoses represented by the ICD-10 diagnosis R42 in people 65 aged years and
      older who visited primary health care because of vertigo and dizziness. METHODS:
      Searches were performed in the computerized medical records of 6 different health
      care centers over the period of 1 year for the ICD-10 diagnosis R42 and the age
      group 65 years and older. Letters were sent to the patients identified with an
      invitation for assessment and physical examination by a physiotherapist. Thirty
      eight patients responded to the letter and were included in the study. All
      patients were assessed by physical examination including the Hallpike maneuver.
      RESULTS: The study group included 13 men and 25 women, 65-94 (median 83) years of
      age. After physical examination, 15 patients were found to have BPPV (confidence
      interval 24-55%). CONCLUSION: In this study, 2 of 5 of the patients with ICD-10
      diagnosis R42 (dizziness and giddiness) had BPPV. BPPV is probably an
      underestimated cause of dizziness/vertigo among elderly patients in primary
      health care.

PMID- 16299420
TI  - Physiological and psychological predictors of walking speed in older community
      dwelling people.
AB  - BACKGROUND: Six-metre walking speed (SMWS) is a commonly used test for measuring
      functional performance in older people. However, apart from lower limb strength,
      few studies have examined the range of physiological and psychological factors
      that influence performance in this test. OBJECTIVE: To investigate the relative
      contributions of a range of sensorimotor, balance and psychological factors to
      SMWS in a large sample of older people. METHODS: 668 community-dwelling people
      aged 75-98 years (mean age 80.1, SD = 4.4) underwent the SMWS test as well as
      quantitative tests of vision, peripheral sensation, strength, reaction time,
      balance, fear of falling, pain and vitality. RESULTS: Many physiological and
      psychological factors were significantly associated with SMWS in univariate
      analyses. Stepwise multiple regression analyses revealed that a composite lower
      limb strength measure (sum of knee extension, knee flexion and ankle dorsiflexion
      muscle strength scores), postural sway, leaning balance as assessed with the
      coordinated stability test, reaction time, edge contrast sensitivity, SF12 body
      pain and vitality scores and age were significant and independent predictors of
      SMWS. Of these measures, the combined lower limb strength measure had the highest
      beta weight indicating it was the most important variable in explaining the
      variance in SMWS. However, the other sensorimotor, balance and psychological
      measures each provided important independent information. The combined set of
      variables explained 40% of the variance in SMWS (multiple r = 0.63). CONCLUSIONS:
      The findings indicate that in community-dwelling older people, self-selected
      walking speed is influenced not only by lower limb strength but also by balance,
      reaction time, vision, pain and emotional well-being.

PMID- 16299421
TI  - Small bowel bacterial overgrowth in symptomatic older people: can it be diagnosed
      earlier?
AB  - BACKGROUND/OBJECTIVES: In older people, small bowel bacterial overgrowth syndrome
      may be a common, but under-diagnosed, cause of diarrhoea and nutrient
      malabsorption. We aim to determine which clinical features and baseline
      laboratory investigations indicate a high likelihood of small bowel bacterial
      overgrowth as defined by a positive glucose breath test. METHODS: A retrospective
      analysis of records for all patients referred for glucose breath test over a 6
      year period to a teaching hospital. RESULTS: Out of 197 referrals, 168 patient
      records were located and analysed (62 male, 106 female; median age 65). Patient
      characteristics predictive of a positive glucose breath test were: increasing age
      (p < 0.01), low serum vitamin B12 (p = 0.02), low serum albumin (p = 0.03),
      previous partial gastrectomy (p < 0.01), previous right hemi-colectomy (p <
      0.01), presence of small bowel diverticulae (p = 0.01) and concurrent use of a
      proton pump inhibitor (p < 0.01). 52.5% (n = 21/40) of patients studied who were
      over 75 years old versus 21.8% (n = 28/128) of those under 75 years old had a
      positive glucose breath test (p < 0.01). The median time to diagnosis, from first
      hospital visit to positive glucose breath test, was 39 weeks. CONCLUSIONS: There
      is often a significant delay in diagnosis of small bowel bacterial overgrowth. We
      suggest that this diagnosis should be considered earlier in the investigative
      algorithm in older patients with indicative symptoms and a predisposing factor
      (including previous partial gastrectomy, previous right hemi-colectomy, small
      bowel diverticulae or use of a proton pump inhibitor) or concurring laboratory
      indices (low vitamin B12 or albumin).

PMID- 16299422
TI  - Social determinants of frailty.
AB  - BACKGROUND: Frailty represents a body-wide set of a linked deterioration that
      occurs with ageing, but is susceptible to active intervention and is reversible.
      The concept of frailty should include broader environmental factors. A
      quantitative measure of frailty, the frailty index (FI), developed for elderly
      Canadians and shown to be valid for an elderly Chinese population, was examined
      for its association with socioeconomic, lifestyle, and social support network
      factors in an elderly Chinese cohort. OBJECTIVE: 2,032 people aged 70 years and
      over recruited by stratified random sampling of the population were surveyed in
      1990-1991, and information obtained regarding physical and functional health,
      psychological factors, lifestyle, socioeconomic and social support factors. The
      FI was constructed from 62 variables covering cognitive, psychological and
      physical health, and tested for association with socioeconomic, lifestyle and
      social support factors using ANOVA and t test. RESULTS: The mean FI for women was
      higher than for men (0.16 +/- 0.08, n = 1,033 vs. 0.13 +/- 0.08, n = 999, p <
      0.001, t test). For men, increasing frailty was observed with non-white collar
      occupations, inadequate expenses, no or little exercise, abstinence from alcohol,
      few relatives or neighbours and no or infrequent participation in helping others.
      For women, little contact with relatives (rather than number of relatives), and
      absence of participation in community/religious activities were additional
      factors. CONCLUSION: FI is influenced by social and environmental factors in
      keeping with the concept of frailty being multi-dimensional. Such a quantitative
      measure may be a useful indicator of the health of elderly populations as well as
      for public health measures to combat frailty.

PMID- 16299423
TI  - Factors affecting the management of outcome in elderly patients with acute
      myocardial infarction particularly with regard to reperfusion. Data from the
      French regional RICO survey.
AB  - BACKGROUND: Acute myocardial infarction (AMI) in elderly patients is often
      unrecognized and associated with poor prognosis. OBJECTIVES: To investigate
      management and efficacy of reperfusion therapy to the elderly patients with AMI.
      METHODS: From the January 1, 2001 to October 31, 2002, 964 patients with AMI were
      included in the French regional RICO survey. The patients were divided into three
      groups: younger (<70 years old), elderly (70-79 years old) and very elderly
      (>or=80 years old). RESULTS: Distribution of groups was 56, 27, and 16%,
      respectively. The longest time delay to first request for medical attention was
      found in the very elderly group (30 and 55 vs. 90 min, respectively, p < 0.05).
      Rate of lysis fell significantly with increasing age (35, 22 and 9%,
      respectively, p < 0.001) but the time delay to lysis was similar for the 3
      groups. The proportion of patients who benefited from primary percutaneaous
      transluminal coronary angioplasty decreased with age (21, 15, 11%, respectively,
      p < 0.001), but time delay to balloon angioplasty was similar and no difference
      in mortality rate was observed between the three groups after reperfusion. The
      incidence of in-hospital cardiovascular events (cardiogenic shock and recurrent
      myocardial infarction/ischemia) and in-hospital mortality increased with age (5,
      13, 17%, respectively, p < 0.001). Moreover, multivariate analysis showed that
      only ejection fraction and Killip >1 were independent predictive factors for in
      hospital cardiovascular mortality, respectively (OR 5.15, 95% CI 2.08-12.74, p <
      0.0001 and OR 3.81, 95% CI 1.90-7.65, p < 0.0001), whereas age, sex, diabetes and
      anterior location were not significant. CONCLUSION: Our data in an unselected
      population indicate that very elderly patients were characterized by increased
      pre-hospital delays and less frequent utilization of reperfusion therapy,
      although no difference in the mortality in reperfused patients could be observed
      between the three age groups.

PMID- 16299424
TI  - Telomere shortening and age estimation in forensic medicine.

PMID- 16299425
TI  - Anxiety in primary care: a frontier for mental health services research.

PMID- 16299426
TI  - Functional impact and health utility of anxiety disorders in primary care
      outpatients.
AB  - OBJECTIVE: The objective of this study was to examine the relative impact of
      anxiety disorders and major depression on functional status and health-related
      quality of life of primary care outpatients. METHOD: Four hundred eighty adult
      outpatients at an index visit to their primary care provider were classified by
      structured diagnostic interview as having anxiety disorders (panic disorder with
      or without agoraphobia, social phobia, and posttraumatic stress disorder;
      generalized anxiety disorder was also assessed in a subset) with or without major
      depression. Functional status, sick days from work, and health-related quality of
      life (including a preference-based measure) were assessed using standardized
      measures adjusting for the impact of comorbid medical illnesses. Relative impact
      of the various anxiety disorders and major depression on these indices was
      evaluated. RESULTS: In multivariate regression analyses simultaneously adjusting
      for age, sex, number of chronic medical conditions, education, and/or poverty
      status, each of major depression, panic disorder, posttraumatic stress disorder,
      and social phobia contributed independently and relatively equally to the
      prediction of disability and functional outcomes. Generalized anxiety disorder
      had relatively little impact on these indices when the effects of comorbid major
      depression were considered. Overall, anxiety disorders were associated with
      substantial decrements in preference-based health states. CONCLUSIONS: These
      observations demonstrate that the presence of each of 3 common anxiety disorders
      (ie, panic disorder, posttraumatic stress disorder, and social phobia)-over and
      above the impact of chronic physical illness, major depression, and other
      socioeconomic factors-contributes in an approximately additive fashion to the
      prediction of poor functioning, reduced health-related quality of life, and more
      sick days from work. Greater awareness of the deleterious impact of anxiety
      disorders in primary care is warranted.

PMID- 16299427
TI  - The costs associated with adverse drug events among older adults in the
      ambulatory setting.
AB  - BACKGROUND: Reducing the rate of adverse drug events in the ambulatory setting
      may require large investments in quality improvement efforts and technologic
      innovations. Little evidence is available on the potential resulting savings.
      OBJECTIVE: The objective of this study was to estimate the costs associated with
      adverse drug events among older adults in the ambulatory setting. RESEARCH
      DESIGN: This study consisted of a 1-year retrospective cohort study among
      Medicare enrollees of a large multispecialty group practice. The study included
      1210 older adults with an adverse drug event. A matched comparison group was
      randomly selected from enrollees with recent healthcare encounters and medication
      dispenses. OUTCOME MEASURE: Difference between estimated costs for medical care
      utilization during the 6 weeks before and 6 weeks beginning on the day of an
      adverse drug event. RESULTS: For all adverse drug events, the increase in
      postevent costs over the preevent period was $1310 (95% confidence interval [CI],
      $625-$1995) greater for those experiencing an adverse drug event than the
      comparison group after controlling for age, sex, comorbidity, number of scheduled
      medications, and having been hospitalized during the preevent period. For
      preventable adverse drug events, the adjusted increase was $1983 (95% CI, $193
      $3773) greater for cases. Based on rates of adverse drug events and these cost
      estimates, 1000 older adults would have annual costs related to adverse drug
      events in the ambulatory setting of $65,631 with $27,365 of this associated with
      preventable events. CONCLUSIONS: Adverse drug events in the ambulatory setting
      substantially increase the healthcare costs of elderly persons.

PMID- 16299428
TI  - How robust are hospital ranks based on composite performance measures?
AB  - BACKGROUND: Composite indices of healthcare performance are an aggregation of
      underlying individual performance measures. They are increasingly being used to
      rank healthcare organizations. Although composite indicators present the "big
      picture" in a way that is easy to interpret, misleading conclusions may be drawn
      if attention is not paid to key methodological issues in their construction.
      OBJECTIVES: We examine variability in performance measures in the context of the
      construction and use of composite measures. We illustrate how variability in the
      underlying data and the resulting composite may undermine the robustness of
      performance measures in health care. We also illustrate how variation in the
      methodological rules applied to aggregate the individual indicators can have an
      important impact on composite scores. METHODS: We use data for 117 English acute
      hospitals to illustrate the generic methodological issues. The variance in
      performance measures is partitioned into "controllable" and "uncontrollable"
      elements. We create a composite index from the underlying performance indicators
      and use Monte Carlo simulations to examine the robustness of the composite.
      RESULTS: Random variation beyond the control of organizations gives rise to
      considerable uncertainty in hospital scores. Composites are also sensitive to
      changes made to the weighting system and to the aggregation rules. Some hospitals
      can jump almost half of the league table as a result of subtle changes.
      CONCLUSIONS: Great care is warranted in interpreting the results of composite
      performance measures. Suggestions for their future development are made.

PMID- 16299429
TI  - Physician decisions to discontinue long-term medications using a two-stage
      framework: the case of growth hormone therapy.
AB  - BACKGROUND: Physician decisions to discontinue prescription medications for
      chronic conditions are fundamental determinants of drug use but have been
      inadequately studied. The decision to stop growth hormone (GH) therapy is an
      important example because of high cost (approximately $26,000/y for a 48-kg
      child), complexity of treatment options, and expansion of patient populations.
      AIM: The aim of this study was to identify the factors that influence physician
      recommendations in the process of discontinuing therapy. DESIGN: A random sample
      of half of U.S. pediatric endocrinologists (n = 265) was mailed a survey that
      included case scenarios of GH-deficient adolescents. Decision options involved a
      2-stage framework to 1) initiate change in ongoing GH therapy (by discussing
      discontinuing GH with the family but not yet stopping treatment), and 2) take
      action to discontinue ongoing GH therapy (by terminating GH or reducing the dose
      to adult maintenance level). MAIN OUTCOME MEASURE: Physician recommendations.
      RESULTS: The response rate was 83.8%. Physiological indices of growth potential
      (growth velocity, bone age) significantly influenced discontinuation decisions
      (both P < 0.001). However, family preference, child's height, and physician
      attitudes exerted independent effects (each P < 0.05). Treatment price had little
      influence. Together, these variables accounted for 60% to 70% of the variation in
      recommendations. Their relative influence differed by stage in the
      discontinuation process. CONCLUSION: The variables in our framework substantially
      explain discontinuation decisions. The data demonstrate the importance of both
      physiological and nonphysiological factors. The results suggest that physicians
      value even small gains as final height approaches, although an additional 20%
      expenditure may be needed to gain the last 1% to 3% of adult height.

PMID- 16299430
TI  - Does the addition of functional status indicators to case-mix adjustment indices
      improve prediction of hospitalization, institutionalization, and death in the
      elderly?
AB  - BACKGROUND: Case-mix adjustment is widely used in health services research to
      ensure that groups being compared are equivalent on variables predicting outcome.
      There has been considerable development and testing of comorbidity indices
      derived from diagnostic codes recorded in administrative databases, but
      increasingly, the benefit of clinical information and patient reported ratings of
      health and functional status is being recognized. One type of information that is
      highly valued but has so far not been captured by administrative health databases
      is functional status indicators (FSI). OBJECTIVE: The purpose of this study was
      to estimate the extent to which prediction of health outcomes can be improved on
      by including information on functional status indicators (FSI). RESEARCH DESIGN:
      The data for the current study was obtained from a clustered randomized trial
      evaluating computerized decision support for managing drug therapy in the
      elderly, conducted from 1997 to 1998. A total of 107 primary care physicians
      participated in this trial and 6465 of their patients (51%) completed a generic
      health status measure-the SF-12-before the intervention. C statistics and R were
      used to compare the predictive value of sociodemographic factors, 2 comorbidity
      indices, and 11 FSI predictor variables derived from the SF-12 and coded
      (possible for 8) using the International Classification of Functioning (ICF).
      RESULTS: Using stepwise logistic regression, FSI, particularly limitation in
      stair climbing or doing moderate activities like housework, were found to be
      strong and independent predictors of all outcomes, even after controlling for
      sociodemographics and comorbidity. CONCLUSION: This study indicates that FSI
      provided as robust a prediction of health events as did complex comorbidity
      indices. Additionally, the ICF coding system provides a mechanism whereby
      information on FSI could be incorporated into administrative databases through
      the use of electronic health records that include a health or functional status
      measure.

PMID- 16299432
TI  - The role of psychiatric diagnosis in satisfaction with primary care: data from
      the department of veterans affairs.
AB  - BACKGROUND: Although patient satisfaction is widely used as a quality indicator,
      most such measures do not account for patient subgroups such as those with
      psychiatric illness. There is also very little data on satisfaction of
      psychiatric patients with their medical care. OBJECTIVE: The objective of this
      study was to assess the role of psychiatric illness in satisfaction with
      outpatient primary care services in the Department of Veterans Affairs (VA).
      METHOD: Data from the VA Customer Feedback Survey (n = 50,532) were merged with
      administrative data to determine diagnoses and other characteristics.
      Satisfaction ratings were compared across psychiatric diagnoses and across
      various aspects of satisfaction with care. RESULTS: After controlling for patient
      characteristics (eg, gender, age, disability, acute vs. routine visit) and
      subjective health, patients with schizophrenia, posttraumatic stress disorder,
      drug abuse, depression, and other psychiatric disorders reported significantly
      lower satisfaction with their outpatient primary care. Dissatisfaction was
      particularly reported for access to care and overall coordination of care.
      CONCLUSIONS: Despite VA characteristics that might be thought to improve
      satisfaction (eg, easier access to specialty mental health services as a result
      of the integrated VA system), patients with psychiatric disorders are
      significantly less satisfied than patients without such disorders. Possible
      explanations include both lower technical quality of care and poorer
      interpersonal communication between providers and patients with mental illness,
      including the negative effects of stigma. These findings highlight the need for
      satisfaction ratings to be case-mix-adjusted, including the incorporation of
      health and mental health diagnoses, and the need for further research that
      elucidates the reasons behind lower satisfaction ratings.

PMID- 16299431
TI  - Beliefs about antidepressant medications in primary care patients: relationship
      to self-reported adherence.
AB  - BACKGROUND: Adherence to medication is unacceptably low in both medical and
      psychiatric disorders. Explanatory models of illness beliefs and behaviors
      suggest that an individual's beliefs about a disorder and its treatment will
      influence their adherence. Given that beliefs about medications may influence
      adherence to antidepressants, we examined beliefs about medications in relation
      to antidepressant adherence in a primary care sample. OBJECTIVE: The purpose of
      this report is to 1) describe beliefs about medication in primary care patients
      prescribed antidepressants for depression; 2) examine the factor structure of the
      Beliefs about Medicines Questionnaire (BMQ) and compare it with the previously
      reported factor structure of the BMQ in medical conditions; and 3) examine the
      association of medication beliefs with self-reported medication adherence.
      RESULTS: Factor analysis indicates that the BMQ is valid in a sample of primary
      care patients receiving treatment for depression and has a similar factor
      structure to that obtained in samples of patients with chronic medical
      conditions. Beliefs about medications are significantly associated with self
      reported adherence. Severity of depressive symptoms and specific concerns about
      antidepressants are significantly associated with self-reported medication-taking
      behavior. Findings suggest that in addition to telling patients how to take their
      medications, primary care physicians should also educate patients about the short
      and long-term effects of the medication, how the medication works, and that
      antidepressants are not addictive.

PMID- 16299433
TI  - Understanding primary care physicians' propensity to assess elderly patients for
      depression using interaction and survey data.
AB  - OBJECTIVE: The objective of this study was to examine primary care physicians'
      propensity to assess their elderly patients for depression using data from
      videotapes and patient and physician surveys. STUDY DESIGN: An observational
      study was informed by surveys of 389 patients and 33 physicians, and 389
      videotapes of their clinical interactions. Secondary quantitative analyses used
      video data scored by the Assessment of Doctor-Elderly Patient Transactions system
      regarding depression assessment. A random-effects logit model was used to analyze
      the effects of patient health, competing demands, and racial and gender
      concordance on physicians' propensity to assess elderly patients for depression.
      RESULTS: Physicians assessed depression in only 14% of the visits. The use of
      formal depression assessment tools occurred only 3 times. White patients were
      almost 7 times more likely than nonwhite patients to be assessed for depression
      (odds ratio [OR], 6.9; P < 0.01). Depression assessment was less likely if the
      patient functioned better emotionally (OR, 0.95; P < 0.01). The propensity of
      depression assessment was higher in visits that covered multiple topics (OR, 1.3;
      P < 0.01) contrary to the notion of competing demands crowding out mental health
      services. Unexpectedly, depression assessment was less likely to occur in gender
      and racially concordant patient-physician dyads. CONCLUSIONS: Primary care
      physicians assessed their elderly patients for depression infrequently. Reducing
      the number of topics covered in visits and matching patients and physicians based
      on race and gender may be counterproductive to depression detection. Informed by
      videotapes and surveys, our findings offer new insights on the actual care
      process and present conclusions that are different from studies based on
      administrative or survey data alone.

PMID- 16299434
TI  - Managed care and systems cost-effectiveness: treatment for depression.
AB  - OBJECTIVE: The objective of this study was to assess the change in system cost
      effectiveness of depression treatment after the introduction of managed care.
      DATA SOURCES/STUDY SETTING: The study population consisted of adults ages 18 to
      69 living in low-income areas of Puerto Rico. STUDY DESIGN: Using a random
      probability sample of the population, 2 waves (1992-1993, 1993-1994) of data were
      collected before implementation of managed care and one wave (1996-1998) after
      implementation. Composite International Diagnostic Interview (CIDI)-generated
      depression diagnoses and Centers for Epidemiologic Studies-Depression (CES-D)
      scale of depressive symptoms scales were used to assess depression. DATA
      COLLECTION/EXTRACTION METHODS: Effectiveness of treatment was defined by
      guideline standards and experts' assessment of the probability of remission
      resulting from treatment. Costs were measured by assigning representative prices
      to each treatment modality. Difference-in-difference (D-in-D) estimators were
      used to assess the impact of managed care on the effectiveness and costs of
      treating depression at the system level for the entire population. PRINCIPAL
      FINDINGS: System cost-effectiveness improved slightly after the introduction of
      managed care, with diminished costs but no significant improvements in
      effectiveness. CONCLUSION: Cost-effectiveness can be measured at the population
      level to assess system changes. Additional incentives and system realignments
      beyond utilization review and diminished treatment costs are necessary to attain
      a more cost-effective system of care.

PMID- 16299435
TI  - Continuity of care practices and substance use disorder patients' engagement in
      continuing care.
AB  - BACKGROUND: Substance use disorder (SUD) patients who engage in more continuing
      care have better outcomes, but information on practices associated with greater
      patient engagement and retention in continuing care remains elusive. OBJECTIVES:
      The objectives of this study were to determine if staff's continuity of care
      practices predict patients' engagement in continuing care in the 6 months after
      discharge from intensive SUD treatment and to determine if the impact of
      continuity of care practices on patients' engagement in continuing care differs
      for patients treated in inpatient/residential versus outpatient programs.
      RESEARCH DESIGN: Staff in 28 Veterans Affairs (VA) intensive SUD treatment
      programs with varying continuity of care practices provided data on 878 patients'
      alcohol and drug problems at treatment entry. At discharge, staff provided data
      on patients' motivation, treatment intensity, and on the continuity of care
      practices they used with each patient. VA administrative databases supplied data
      on patients' subsequent engagement in continuing care. Mixed-effects modeling was
      used to examine predictors of patients' engagement in care. RESULTS: Patients in
      outpatient programs who received more continuity of care engaged in continuing
      care significantly longer. More highly motivated outpatients, those with fewer
      alcohol problems at treatment entry, and patients who used VA services in the
      year before treatment also remained in continuing care longer. These findings did
      not hold for patients treated in inpatient/residential programs. CONCLUSIONS:
      Continuity of care practices predicted engagement in continuing care only for
      patients treated in outpatient SUD programs. More research is needed to identify
      effective continuity of care practices for patients treated in
      inpatient/residential programs.

PMID- 16299436
TI  - The influence of display and statistical factors on the interpretation of
      metaanalysis results by physicians.
AB  - OBJECTIVE: The objective of this study was to determine the extent to which
      various factors affect the interpretation of metaanalytic results by physicians.
      STUDY DESIGN: A sample of 120 physicians, selected from The Royal College of
      Physicians and Surgeons of Canada (RCPSC), was randomly assigned to 1 of 6 groups
      (n = 20) created from a combination of 3 summary measures and 2 levels of disease
      severity. The intervention consisted of a written scenario and 4 individual
      displays of metaanalyses (M-A), each followed by questions related to the
      interpretation of results of M-A. Two final questions examined statistical
      familiarity/proficiency with the summary measures used. DATA ANALYSIS: Analyses
      of variance examined main effects and interactions among 4 factors: summary
      measure, disease severity, effect size, and statistical consistency of the
      studies comprising the metaanalysis. Two outcomes were examined: interpretation
      of the treatment effect and confidence in the interpretation of the treatment
      effect. PRINCIPAL FINDINGS: Physicians were more likely to favor treatment when
      the results of the primary randomized, controlled trials (RCTs) were
      statistically homogeneous (P = 0.001) and when the overall effect size was large
      (P = 0.001). Also, physicians were more likely to be confident when the results
      were homogeneous (P = 0.001) and when effect size was large (P = 0.000).
      Interactions also revealed that the effect of statistical consistency of
      contributing to RCTs was greatest when data were presented as risk difference for
      treatment outcome (P = 0.026) and when effect size was small (P = 0.000).
      CONCLUSIONS: The interpretation of metaanalytic displays is influenced by the
      overall effect size of M-A, the statistical consistency of the contributing RCTs,
      and interactions of these factors with display factors.

PMID- 16299437
TI  - Service collaboration and hospital cost performance: direct and moderating
      effects.
AB  - BACKGROUND: Growing reliance on service provision through systems and networks
      creates the need to better understand the nature of the relationship between
      service collaboration and hospital performance and the conditions that affect
      this relationship. OBJECTIVE: We examine 1) the effects of service provision
      through health systems and health networks on hospital cost performance and 2)
      the moderating effects of market conditions and service differentiation on the
      collaboration-cost relationship. RESEARCH DESIGN: We used moderated regression
      analysis to test the direct and moderating effects. Data on 1368 private
      hospitals came from the 1998 AHA Annual Survey, Medicare Cost Reports, and
      Solucient. MEASURES: Service collaboration was measured as the proportion of
      hospital services provided at the system level and at the network level. Market
      conditions were measured by the levels of managed care penetration and
      competition in the hospital's market. RESULTS: The proportion of hospital
      services provided at the system level had a negative relationship with hospital
      cost. The relationship was curvilinear for network use. Degree of managed care
      penetration moderated the relationship between network-based collaboration and
      hospital cost. CONCLUSION: The benefits of service collaboration through systems
      and networks, as measured by reduced cost, depend on degree of collaboration
      rather than mere membership. In loosely structured collaborations such as
      networks, costs reduce initially but increase later as the extent of
      collaboration increases. The effect of network-based collaboration is also
      tempered by managed care penetration. These effects are not seen in more tightly
      integrated forms such as systems.

PMID- 16299438
TI  - Depression and other mental health diagnoses after stroke increase inpatient and
      outpatient medical utilization three years poststroke.
AB  - OBJECTIVE: Poststroke depression (PSD) has been linked to negative outcomes,
      including mortality and decreased functioning. However, the effect of PSD and
      other mental health conditions on inpatient and outpatient healthcare utilization
      after stroke has not been examined. The primary objective of this study was to
      evaluate the relationship between PSD and healthcare utilization after stroke.
      The secondary objective was to evaluate the relationship between other mental
      health diagnoses and medical utilization after stroke. METHOD: We examined 3
      years of poststroke healthcare utilization data in a national cohort of veterans
      with ischemic stroke. Mental health diagnoses were identified with inpatient
      International Classification of Diseases, 9th Revision codes. Multivariate
      analysis of variance was used to compare patient characteristics and multivariate
      linear regression to model utilization in: 1) patients with PSD, 2) patients
      diagnosed with other mental health conditions poststroke, and 3) patients with no
      mental health diagnosis. RESULTS: Of 51,119 veterans identified, 2405 (5%)
      received a PSD diagnosis and 2257 (4%) received a diagnosis of another mental
      health condition after their stroke. Patients with PSD had significantly more
      inpatient hospitalization days and outpatient visits than those without any
      mental health diagnosis, even after adjusting for the number of mental health
      clinic visits. Likewise, patients diagnosed with other mental health diagnoses
      had greater medical utilization than patients without any mental health
      diagnosis. Both PSD and other mental health diagnoses independently predicted
      medical utilization. CONCLUSION: Mental health diagnosis after stroke increases
      inpatient and outpatient healthcare utilization in the first 3 years poststroke.
      Additional biologic and psychosocial factors should be investigated.

PMID- 16299441
TI  - [Endoscopically assisted retro-caroncular approach for medial wall fracture of
      the orbit: preliminary study].
AB  - PURPOSE: The purpose of this study was to present our experience of
      endoscopically assisted retro-caruncular approach of medial wall fracture of
      orbital bone, notably concerning the accessibility and visibility. METHODS: Five
      consecutive patients (4 men and 1 woman) with recent fracture (1 to 3 days),
      underwent medial wall reconstruction with a polydioxanone plate, endoscopically
      assisted via a retro-caruncular approach. The surgical technique and its results
      are described. Helpful hints are discussed. RESULTS: The plate did not have to be
      bent for introduction. Operative time was less than an hour for all patients. All
      patients were discharged the day after surgery. All experienced a mild degree of
      postoperative edema-related diplopia. None had persistent or secondary diplopia
      or enophthalmos at the one and six-month follow-up visits, respectively. Other
      postoperative complications, such as hematoma, nerve injury, or infection were
      not observed. All patients were satisfied with the outcome and especially the
      cosmetic result. DISCUSSION: The retro-caruncular approach with adjunctive
      endoscopic surgery should be the gold standard for posttraumatic isolated medial
      wall reconstruction of the orbit.

PMID- 16299443
TI  - [Arthroscopy of the temporomandibular joint].

PMID- 16299442
TI  - [Current data and perspectives in minimally invasive video-assisted head and neck
      surgery: example of endoscopic exploration of the submandibular region].
AB  - The purpose of this study was to review the current status of research in this
      field and to describe the endoscopic technique for resection of the submandibular
      gland: a 15-mm incision is sufficient for the endoscopic material and gland
      resection without insufflation. The wound is minimal and the dissection is not
      traumatic. This innovating technique enables a magnified view of the structures
      providing an excellent teaching method.

PMID- 16299444
TI  - [Microinvasive endonasal surgery: contribution of endoscopy to maxillofacial
      surgery].
AB  - Video-assisted endonasal endoscopic surgery is used for a constantly increasing
      number of indications, replacing more invasive external approaches. Indications
      include chronic bacterial and fungal sinusitis, nasosinus polyposis, mucocele,
      inverted papilloma, and lacrimal duct stenosis. This microinvasive technique
      offers the advantage of preserving the physiological properties of the mucosa
      while assuring proper ventilation of the nasal and sinus cavities. We discuss the
      technical basis of this new surgical option used by ear-nose-throat specialists
      and maxillofacial surgeons. We focus on turbinai, septal, maxillary, and lacrimal
      surgery but do not discuss the more specific rhinology areas such as
      ethmoidectomy, sphenoidotomy or frontal surgery. The main procedures are
      described together with indications and expected results.

PMID- 16299445
TI  - [Salivary gland endoscopy: new limits?].
AB  - Sialendoscopy is a new minimally invasive technique allowing exploration of the
      submandibular and parotid ducts with treatment for sialolithiasis and stenosis.
      Used for diagnostic purposes, sialendoscopy may be an alternative to classical
      radiological methods. As an interventional technique, it allows a significant
      reduction in the number of indications for submandibular and parotid resections.

PMID- 16299446
TI  - [Diagnostic and interventional sialendoscopy].

PMID- 16299447
TI  - [Atypical fissuration of the tongue].

PMID- 16299448
TI  - [Erosive oral lichen planus and tacrolimus ointment].

PMID- 16299449
TI  - Drugs for epilepsy.

PMID- 16299450
TI  - Drugs for rheumatoid arthritis.

PMID- 16299451
TI  - Antiviral drugs for prophylaxis and treatment of influenza.

PMID- 16299452
TI  - Finasteride and minoxidil for alopecia revisited.

PMID- 16299453
TI  - Surgical ablation of atrial fibrillation.

PMID- 16299454
TI  - Surgical treatment for ischemic mitral regurgitation: strategy for a tethered
      valve.
AB  - Recently, ischemic mitral regurgitation (IMR) has been shown to be an individual
      risk factor for ischemic heart disease. The main mechanism of IMR is tethering of
      the leaflet secondary to left ventricular (LV) dilatation. In this situation,
      surgical treatment for IMR has been limited to ring annuloplasty with varying
      degrees of effectiveness. However, mid-term follow-up studies have shown that the
      results obtained with this approach are not satisfactory. Therefore, there has
      been a need to develop additional techniques to achieve more secure repair of
      IMR. The characteristics of the mitral leaflet configuration in IMR are apical
      displacement of the leaflets relative to the annulus, concavity of the leaflets,
      and a dilated annulus. Our basic strategy for a tethered mitral valve is rigid
      ring annuloplasty and inward correction of the outwardly displaced papillary
      muscle. For the latter correction, we employ the overlapping method or septal
      anterior ventricular exclusion (SAVE) procedure for LV volume reduction in cases
      of broad antero-septal infarction, or elevate the posterior papillary muscle by
      folding the LV wall at the root of the posterior papillary muscle via a small
      incision in the inferior wall in cases of infero-posterior infarction. An
      additional procedure is chordal cutting in combination with rigid ring
      annuloplasty and papillary muscle imbrication in combination with LV volume
      reduction. We have successfully combined these methods with the aid of detailed
      echocardiographic studies in individual patients. However, long-term follow-up
      will be necessary before this approach can be routinely adopted.

PMID- 16299455
TI  - Effect of substituting allogenic blood transfusion with autologous blood
      transfusion on outcomes after radical oesophagectomy for cancer.
AB  - BACKGROUND: The oncologic benefit of avoiding allogenic blood transfusion in
      oesophageal cancer resection has not been studied. METHODS: The medical records
      of 68 patients (Auto group) who underwent a potentially curative oesophageal
      cancer resection without allogenic blood transfusion from 1996 to 1999 receiving
      800 g of autologous blood donated preoperatively, and 97 patients (Allo group)
      who underwent the same operation with allogenic blood transfusion from 1990 to
      1995 were compared. RESULTS: There were no differences in age, gender, stage of
      disease, number of retrieved nodes, or perioperative hemoglobin concentration
      between the two groups. The survival of the 45 patients with nodal involvement in
      the Auto group was better than that of the 59 patients in the Allo group
      (p=0.0435), and the survival of the 35 patients with T3 or T4 lesions in the Auto
      group was better than that of the 61 patients in the Allo group (p=0.0408).
      According to logistic regression analysis, allogenic blood transfusion correlated
      with tumour recurrence in patients with either nodal involvement or a T3-4
      lesion. The natural killer cell activity remained higher in the Auto group than
      in the Allo group (p<0.05). CONCLUSION: Avoidance of allogenic blood transfusion
      favorably effected the survival of patients with oesophageal cancer at risk for
      recurrence.

PMID- 16299456
TI  - Is an increase in lactate concentration associated with cardiac dysfunction after
      the Fontan procedure?
AB  - PURPOSE: To investigate how blood lactate concentration changes in the early
      postoperative course after the Fontan procedure, and whether such a change is
      associated with postoperative hemodynamics. MATERIALS AND METHODS: Eight
      pediatric patients who underwent the Fontan procedure for congenital heart
      disease were included. Enrollment criteria were body weight >10 kg and staged
      Fontan procedure following the bidirectional Glenn procedure. Blood lactate
      concentration and central venous oxygen saturation (SvO2) were measured at five
      points: before skin incision, upon intensive care unit (ICU) admission, 15
      minutes before, 15 minutes after, and 2 hours after extubation. Cardiac index
      (CI) was continuously monitored using the pulse contour technique. RESULTS:
      Lactate concentration increased in the ICU, peaking from 15 minutes before (2.7+/
      1.3 mmol/L) to 15 minutes after (3.0+/-1.3 mmol/L) extubation. Values returned to
      normal parameters (1.0+/-0.1 mmol/L) within 48 hours. The CI values were also
      higher immediately after extubation (4.0+/-0.6 L/min/m2) than at ICU admission
      (3.3+/-0.6 L/min/m2) and before extubation (3.6+/-0.6 L/min/m2) (p=0.012). No
      significant change in central SvO2 or blood pressure (BP) was evident during the
      study period. CONCLUSION: In the early postoperative period after the Fontan
      procedure, blood lactate concentration increased temporarily around the time of
      extubation but the increase was not associated with hemodynamic deterioration.

PMID- 16299457
TI  - Mechanical ventricular circulatory support in children; Bad Oeynhausen
      experience.
AB  - INTRODUCTION: Recently various mechanical circulatory support systems are being
      used all over the world, nevertheless the size of the devices limits the
      implantation in pediatric cases. Accordingly we report our experiences with
      assist devices applied for pediatric patients. PATIENTS AND METHODS: Twenty-nine
      children underwent mechanical circulatory support implantation operation. The
      diagnoses of preoperation were dilated cardiomyopathy in 16, congenital heart
      disease in 12 and allograft dysfunction in 1. RESULTS: From November 1987 to
      January 2004 we implanted 7 LVAD, 11 BVAD and 11 ECMO in pediatric patients. The
      29 patients were supported from 11 to 231 days (mean 32.3 days). Three children
      were supported by Thoratec LVAD. Biventricular Thoratec VAD was used in 3
      children. Three children were supported by Medos-HIA system LVAD, and 8 children
      by biventricular VAD using the Medos-HIA system. One child was supported by
      Novacor LVAD. Fourteen children were supported by ECMO. We succeeded in heart
      transplantation in 10 cases, but lost 16 children during the support. Bleeding
      occurred in 7 cases, thrombosis occurred in 6 cases, infection occurred in 8
      cases, pneumothorax occurred in 3 cases and neurological deficit occurred in 2
      cases. CONCLUSION: The development of assist device for children which has long
      durability and small in size as a future subject is desired. Further clinical and
      experimental research and application of those assist devices for children are in
      progress.

PMID- 16299458
TI  - Successful treatment of a patient with penetrating injury of the esophagus and
      brachiocephalic artery due to migration of Kirschner wires.
AB  - Pins and wires offer the simplest and most effective tools for managing bone
      fractures and dislocations. Migration of these devices within the chest is rare,
      but can cause serious problems. The spontaneous migration of Kirschner wires from
      the right clavicle to the mediastinum resulted in penetrating injury of the
      esophagus and pseudo-aneurysm of the brachiocephalic artery in an 84-year-old
      patient. Two Kirschner wires were removed via a vertical incision on the right
      shoulder without thoracotomy and the brachiocephalic artery was replaced with a
      Dacron graft.

PMID- 16299459
TI  - A surgical case of lung cancer in a patient with the left superior and inferior
      pulmonary veins forming a common trunk.
AB  - The anatomical abnormalities of the pulmonary veins may have a serious impact on
      complications that may arise during pulmonary lobectomy. We present a surgical
      case of left lung cancer in a patient, who was a 69-year-old male, with the left
      superior and inferior pulmonary veins forming a common trunk outside the
      pericardium. In this present case, because of extensive adhesions, incomplete
      lobulation, and tumor infiltration of the main pulmonary artery, we could not
      identity the common trunk with certainty before excising the left upper lobe.
      Although this patient was fortunately discharged without complications, there was
      no choice but to perform pneumonectomy because of the interruption of the
      inferior pulmonary vein. Retrospectively, the preoperative CT films showed the
      anatomical anomalies involving the pulmonary veins. However, since the length of
      the common trunk outside the pericardium was short and the inferior pulmonary
      vein was thinner than usual and its venous distribution conformed to a normal
      structure, the anatomy appeared normal. In excising the pulmonary lobe, it is
      mandatory to ascertain the distribution of the vascular system prior to surgery.

PMID- 16299461
TI  - Unexpected hemodynamic deterioration and mitral regurgitation due to a tissue
      stabilizer during left anterior descending coronary anastomosis in off-pump
      coronary artery bypass graft surgery.
AB  - We have experienced three rare cases of hemodynamic deterioration and transient
      mitral regurgitation (MR) induced by a suction-type tissue stabilizer during the
      left internal thoracic artery (LITA)-to-LAD (left anterior descending) coronary
      artery anastomosis. Transesophageal echocardiogram (TEE) showed new or worsening
      MR during the placement of a tissue stabilizer. In all three cases, the
      positioning of the stabilizer was difficult to secure a good surgical field,
      because the LAD coronary artery migrated deep into the myocardium. This
      anatomical variation seemed to require a stronger fixation of the stabilizer to
      the heart. We concluded that compression of the left ventricular (LV) wall may
      have possibly caused morphologic changes of the LV and the distortion of the
      annulus of the mitral valve. These changes are thought to have caused decreased
      LV filling and the MR, which led to an unexpected hemodynamic deterioration.

PMID- 16299460
TI  - Simultaneous repair of pectus excavatum and tetralogy of fallot: report of a
      case.
AB  - We report an 18-month-old boy with the association of pectus excavatum and
      tetralogy of Fallot (TOF). We successfully performed simultaneous pectus repair
      using sternal elevation without any prosthetic support and total correction of
      TOF after a prior modified Blalock-Taussig shunt. Retracting a divided costo
      sternal complex with a rectus abdominal flap away from the operative field before
      the cardiac operation provided excellent surgical exposure. The modified Blalock
      Taussig shunt prior to the combined repair prevented life-threatening hypoxic
      spells during dissection of the deformed sternum and costochondral cartilages
      before institution of cardiopulmonary bypass.

PMID- 16299462
TI  - A case of aortic valve replacement with St. Jude Medical Regent valve (first
      implant in Japan).
AB  - The St. Jude Medical (SJM) Regent valve was developed as a new mechanical valve
      by improving the conventional SJM valve. The effective orifice area is wider than
      that of Hemodynamic Plus (HP) series. The efficacy of the new valve has been
      reported in Europe and the United States. On October 26, 2004, we first performed
      aortic valve replacement (AVR) with the SJM Regent valve for aortic valve
      stenosis in Japan. A 64-year-old female was admitted to our hospital with dyspnea
      on exertion. She was diagnosed with aortic valve stenosis. She underwent AVR with
      a 17 mm SJM Regent valve. According to the results of echocardiography conducted
      two months postoperatively, the peak pressure gradient of the prosthetic valve
      was 32.0 mmHg, the mean pressure gradient was 13.2 mmHg, and the effective
      orifice area index (EOAI) was 0.92 cm2/m2. Cinefluoroscopy showed the valve
      opening angle of 85 degrees indicating full opening. She was discharged 15 days
      after surgery without complications. As demonstrated by the present case,
      implantation of a 17 mm SJM Regent valve produced a satisfactory result reflected
      by lower pressure gradient and absence of patient-prosthetic mismatch. In the
      future, the new valve is expected to be the optimum mechanical valve for a narrow
      annulus.

PMID- 16299463
TI  - Endovascular stent-grafting for thoracoabdominal aortic aneurysm following bypass
      grafting to superior mesenteric and celiac arteries: report of two cases.
AB  - Two high-risk patients underwent an endovascular stent-grafting for
      thoracoabdominal aortic aneurysms (TAAA) following bypass-grafting to the
      visceral arteries. The first patient was a 73-year-old woman with severe ischemic
      heart disease (IHD) and chronic respiratory failure. The second patient was a 59
      year-old woman with myelodysplastic syndromes (MDSs) and hepatic cell carcinoma
      (HCC). In general, TAAA is not considered to be indicated for endovascular stent
      grafting because of the need to revascularize the visceral vessels. However, in
      some selected cases, such as the two cases presented herein, endovascular stent
      grafting combined with bypass-grafting of the visceral arteries can be a feasible
      and a less-invasive alternative to conventional surgery.

PMID- 16299464
TI  - A single-stage operation for abdominal aortic aneurysm with concomitant
      colorectal carcinoma.
AB  - The coexistence of abdominal aortic aneurysm (AAA) and colorectal carcinoma needs
      special operative consideration. A single-stage operation for concomitant AAA and
      colorectal carcinoma has been thought to increase the risk of vascular prosthetic
      graft infection. We report two patients who received a single-stage operation for
      AAA and colorectal carcinoma. The first patient had a fusiform aneurysm of the
      infrarenal aorta. The second patient had a saccular aneurysm of the infrarenal
      aorta and a fusiform aneurysm of the left internal iliac artery. Both patients
      had left-sided colorectal carcinoma classified as Dukes' stage B. The two
      patients underwent a single-stage operation with Hartmann's procedure to avoid
      graft infection caused by anastomotic leakage. They tolerated the operation and
      had no postoperative complications including graft infection. A single-stage
      operation for concomitant AAA and left-sided colorectal carcinoma could be safely
      performed with Hartmann's procedure in two cases.

PMID- 16299465
TI  - Late rupture of knitted Dacron graft.
AB  - An 87-year-old man underwent aorto-bifemoral bypass using a bifurcated Bionit II
      knitted Dacron graft for high aortic occlusion in 1987 at another hospital. In
      November, 2004, he was admitted to our institution because of difficulty in
      walking due to swelling and tenderness in the right groin. Computed tomography
      (CT) scan indicated bilateral aneurysms of the grafts in the groins. The size of
      the right and left aneurysms were 73 mm and 52 mm, respectively. Angiography
      showed some extravasation in the right thigh. We performed surgical replacement
      of all the dilated parts with new ringed-Dacron grafts. We report a rare case of
      late rupture of bifurcated Sauvage Bionit II Dacron graft.

PMID- 16299466
TI  - Successful surgical treatment for aneurysm of splenic artery with anomalous
      origin.
AB  - The splenic artery is the third common site of an infrarenal abdominal arterial
      aneurysm after the abdominal aorta and iliac arteries, and the most common site
      of a visceral artery aneurysm. It is a rare, but clinically important form of
      vascular disease with the potential for life-threatening rupture. We report a 64
      year-old woman with a splenic artery aneurysm. Though she was asymptomatic,
      calcification around the left upper quadrant was incidentally detected. A
      saccular aneurysm with calcification located in the proximal portion of the
      splenic artery was detected by computed tomography (CT). Anomalous origin of the
      splenic artery, from the superior mesenteric artery (SMA), was also detected.
      Aneurysmal resection without splenectomy was carried out successfully. A suitable
      approach to aneurysms must be selected in each case, because the splenic artery
      exhibits congenital anomaly in 10% of all the people.

PMID- 16299467
TI  - A new end graft holder for coronary artery bypass grafting.
AB  - This article describes the construction and use of a new end graft holder during
      coronary artery bypass grafting (CABG). The instrument consists of a pinching
      device attached to a flexible arm and a fixation clamp. This device provides
      secure stabilization and enables excellent positioning of the graft without
      producing graft injury.

PMID- 16299468
TI  - The Notch 'gospel'.

PMID- 16299469
TI  - Preventing illicit liaisons in Poland.

PMID- 16299470
TI  - The wild-type Schizosaccharomyces pombe mat1 imprint consists of two
      ribonucleotides.
AB  - The imprint at the mat1 locus of Schizosaccharomyces pombe acts to initiate the
      replication-coupled recombination event that underlies mating-type switching.
      However, the nature of the imprint has been an area of dispute. Two alternative
      models have been proposed: one stated that the imprint is a nick in the DNA,
      whereas our data suggested that it consists of one or two ribonucleotides
      incorporated into the otherwise intact DNA duplex. Here, we verify key
      predictions of the RNA model by characterization of wild-type genomic DNA
      purified under conditions known to hydrolyse DNA-RNA-DNA hybrid strands. First,
      we observe one-nucleotide gap at the hydrolysed DNA, as expected from the
      presence of two ribonucleotides. Second, using a novel assay based on ligation
      mediated PCR, a 3'-terminal ribonucleotide is detected at the hydrolysed imprint.
      Our observations allow the unification of available data sets characterizing the
      wild-type imprint.

PMID- 16299473
TI  - FlAsHlights on bacterial virulence proteins.

PMID- 16299472
TI  - Frog transgenesis made simple.

PMID- 16299471
TI  - ARE-mRNA degradation requires the 5'-3' decay pathway.
AB  - As an important mode of suppressing gene expression, messenger RNAs containing an
      AU-rich element (ARE) in the 3' untranslated region are rapidly degraded in the
      cytoplasm. ARE-mediated mRNA decay (AMD) is initiated by deadenylation, and in
      vitro studies have indicated that subsequent degradation occurs in the 3'-5'
      direction through a complex of exonucleases termed the exosome. An alternative
      pathway of mRNA degradation occurs at processing bodies, cytoplasmic foci that
      contain decapping enzymes, the 5'-3' exonuclease Xrn1 and the Lsm1-7 heptamer. To
      determine which of the two pathways is important for AMD in live cells, we
      targeted components of both pathways using short interfering RNA in human HT1080
      cells. We show that Xrn1 and Lsm1 are essential for AMD. On the other side, out
      of three exosome components tested, only knockdown of PmScl-75 caused a strong
      inhibition of AMD. Our results show that mammalian cells, similar to yeast,
      require the 5'-3' Xrn1 pathway to degrade ARE-mRNAs.

PMID- 16299474
TI  - Fluorescence microscopy today.
AB  - Fluorescence microscopy has undergone a renaissance in the last decade. The
      introduction of green fluorescent protein (GFP) and two-photon microscopy has
      allowed systematic imaging studies of protein localization in living cells and of
      the structure and function of living tissues. The impact of these and other new
      imaging methods in biophysics, neuroscience, and developmental and cell biology
      has been remarkable. Further advances in fluorophore design, molecular biological
      tools and nonlinear and hyper-resolution microscopies are poised to profoundly
      transform many fields of biological research.

PMID- 16299475
TI  - A guide to choosing fluorescent proteins.
AB  - The recent explosion in the diversity of available fluorescent proteins (FPs)
      promises a wide variety of new tools for biological imaging. With no unified
      standard for assessing these tools, however, a researcher is faced with difficult
      questions. Which FPs are best for general use? Which are the brightest? What
      additional factors determine which are best for a given experiment? Although in
      many cases, a trial-and-error approach may still be necessary in determining the
      answers to these questions, a unified characterization of the best available FPs
      provides a useful guide in narrowing down the options.

PMID- 16299476
TI  - Fluorescence microscopy.
AB  - Although fluorescence microscopy permeates all of cell and molecular biology,
      most biologists have little experience with the underlying photophysical
      phenomena. Understanding the principles underlying fluorescence microscopy is
      useful when attempting to solve imaging problems. Additionally, fluorescence
      microscopy is in a state of rapid evolution, with new techniques, probes and
      equipment appearing almost daily. Familiarity with fluorescence is a prerequisite
      for taking advantage of many of these developments. This review attempts to
      provide a framework for understanding excitation of and emission by fluorophores,
      the way fluorescence microscopes work, and some of the ways fluorescence can be
      optimized.

PMID- 16299477
TI  - Optical sectioning microscopy.
AB  - Confocal scanning microscopy, a form of optical sectioning microscopy, has
      radically transformed optical imaging in biology. These devices provide a
      powerful means to eliminate from images the background caused by out-of-focus
      light and scatter. Confocal techniques can also improve the resolution of a light
      microscope image beyond what is achievable with widefield fluorescence
      microscopy. The quality of the images obtained, however, depends on the user's
      familiarity with the optical and fluorescence concepts that underlie this
      approach. We describe the core concepts of confocal microscopes and important
      variables that adversely affect confocal images. We also discuss data-processing
      methods for confocal microscopy and computational optical sectioning techniques
      that can perform optical sectioning without a confocal microscope.

PMID- 16299478
TI  - Deep tissue two-photon microscopy.
AB  - With few exceptions biological tissues strongly scatter light, making high
      resolution deep imaging impossible for traditional-including confocal
      fluorescence microscopy. Nonlinear optical microscopy, in particular two photon
      excited fluorescence microscopy, has overcome this limitation, providing large
      depth penetration mainly because even multiply scattered signal photons can be
      assigned to their origin as the result of localized nonlinear signal generation.
      Two-photon microscopy thus allows cellular imaging several hundred microns deep
      in various organs of living animals. Here we review fundamental concepts of
      nonlinear microscopy and discuss conditions relevant for achieving large imaging
      depths in intact tissue.

PMID- 16299479
TI  - Fiber-optic fluorescence imaging.
AB  - Optical fibers guide light between separate locations and enable new types of
      fluorescence imaging. Fiber-optic fluorescence imaging systems include portable
      handheld microscopes, flexible endoscopes well suited for imaging within hollow
      tissue cavities and microendoscopes that allow minimally invasive high-resolution
      imaging deep within tissue. A challenge in the creation of such devices is the
      design and integration of miniaturized optical and mechanical components. Until
      recently, fiber-based fluorescence imaging was mainly limited to epifluorescence
      and scanning confocal modalities. Two new classes of photonic crystal fiber
      facilitate ultrashort pulse delivery for fiber-optic two-photon fluorescence
      imaging. An upcoming generation of fluorescence imaging devices will be based on
      microfabricated device components.

PMID- 16299480
TI  - Mutation discovery in bacterial genomes: metronidazole resistance in Helicobacter
      pylori.
AB  - We developed a microarray hybridization-based method, 'comparative genome
      sequencing' (CGS), to find mutations in bacterial genomes and used it to study
      metronidazole resistance in H. pylori. CGS identified mutations in several genes,
      most likely affecting metronidazole activation, and produced no false positives
      in analysis of three megabases. We conclude that CGS identifies mutations in
      bacterial genomes efficiently, should enrich understanding of systems biology and
      genome evolution, and help track pathogens during outbreaks.

PMID- 16299481
TI  - Positional proteomics: selective recovery and analysis of N-terminal proteolytic
      peptides.
AB  - Bottom-up proteomics is the analysis of peptides derived from single proteins or
      protein mixtures, and because each protein generates tens of peptides, there is
      scope for controlled reduction in complexity. We report here a new strategy for
      selective isolation of the N-terminal peptides of a protein mixture, yielding
      positionally defined peptides. The method is tolerant of several fragmentation
      methods, and the databases that must be searched are substantially less complex.

PMID- 16299482
TI  - Secretion of type III effectors into host cells in real time.
AB  - Type III secretion (T3S) systems are key features of many gram-negative bacteria
      that translocate T3S effector proteins directly into eukaryotic cells. There, T3S
      effectors exert many effects, such as cellular invasion or modulation of host
      immune responses. Studying spatiotemporal orchestrated secretion of various
      effectors has been difficult without disrupting their functions. Here we
      developed a new approach using Shigella flexneri T3S as a model to investigate
      bacterial translocation of individual effectors via multidimensional time-lapse
      microscopy. We demonstrate that direct fluorescent labeling of tetracysteine
      motif-tagged effectors IpaB and IpaC is possible in situ without loss of
      function. Studying the T3S kinetics of IpaB and IpaC ejection from individual
      bacteria, we found that the entire pools of IpaB and IpaC were released
      concurrently upon host cell contact, and that 50% of each effector was secreted
      in 240 s. This method allows an unprecedented analysis of the spatiotemporal
      events during T3S.

PMID- 16299485
TI  - Stable expression of fluorescently tagged proteins for studies of mitosis in
      mammalian cells.

PMID- 16299483
TI  - High-throughput screening of effective siRNAs from RNAi libraries delivered via
      bacterial invasion.
AB  - Use of RNA interference (RNAi) as a reverse genetics tool for silencing genes in
      mammalian cells is achieved by in vitro transfection of small interfering RNAs
      (siRNAs). For a target gene, several siRNAs must be designed according to the
      empirical rules. We demonstrated that functional short hairpin RNAs (shRNAs)
      could be synthesized in Escherichia coli and delivered directly via bacterial
      invasion to the near entirety of a mammalian cell population to trigger RNAi.
      Furthermore, using a luciferase-target gene transcript, we identified effective
      shRNAs and siRNAs from RNAi libraries delivered conveniently through bacterial
      invasion in 96-well plates without need for preparation, purification and
      transfection of shRNAs. Notably, several of the most highly effective shRNAs and
      siRNAs identified do not fit the empirical rules commonly used for siRNA design,
      suggesting that this approach is a powerful tool for RNAi research, and could be
      used complementarily to the empirical rules for RNAi applications.

PMID- 16299484
TI  - Transgenic Xenopus laevis embryos can be generated using phiC31 integrase.
AB  - Bacteriophage phiC31 encodes an integrase that can mediate the insertion of
      extrachromosomal DNA into genomic DNA. Here we show that the coinjection of mRNA
      encoding phiC31 integrase with plasmid DNA encoding the green fluorescent protein
      (GFP) can be used to generate transgenic X. laevis embryos. Despite integration
      into the genome, appropriate promoter expression required modification of the
      reporter plasmid by bracketing the GFP reporter gene with tandem copies of the
      chicken beta-globin 5' HS4 insulator to relieve silencing owing to chromatin
      position effects. These experiments demonstrate that the integration of insulated
      gene sequences using phiC31 integrase can be used to efficiently create
      transgenic embryos in X. laevis and may increase the practical use of phiC31
      integrase in other systems as well.

PMID- 16299493
TI  - ACNP 44th Annual Meeting, December 11-15, 2005, Waikoloa, Hawaii. Abstracts.

PMID- 16299494
TI  - A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage
      checkpoint recovery.
AB  - One of the earliest marks of a double-strand break (DSB) in eukaryotes is serine
      phosphorylation of the histone variant H2AX at the carboxy-terminal SQE motif to
      create gammaH2AX-containing nucleosomes. Budding-yeast histone H2A is
      phosphorylated in a similar manner by the checkpoint kinases Tel1 and Mec1 (ref.
      2; orthologous to mammalian ATM and ATR, respectively) over a 50-kilobase region
      surrounding the DSB. This modification is important for recruiting numerous DSB
      recognition and repair factors to the break site, including DNA damage checkpoint
      proteins, chromatin remodellers and cohesins. Multiple mechanisms for eliminating
      gammaH2AX as DNA repair completes are possible, including removal by histone
      exchange followed potentially by degradation, or, alternatively,
      dephosphorylation. Here we describe a three-protein complex (HTP-C, for histone
      H2A phosphatase complex) containing the phosphatase Pph3 that regulates the
      phosphorylation status of gammaH2AX in vivo and efficiently dephosphorylates
      gammaH2AX in vitro. gammaH2AX is lost from chromatin surrounding a DSB
      independently of the HTP-C, indicating that the phosphatase targets gammaH2AX
      after its displacement from DNA. The dephosphorylation of gammaH2AX by the HTP-C
      is necessary for efficient recovery from the DNA damage checkpoint.

PMID- 16299495
TI  - An acidic protein aligns magnetosomes along a filamentous structure in
      magnetotactic bacteria.
AB  - Magnetotactic bacteria are widespread aquatic microorganisms that use unique
      intracellular organelles to navigate along the Earth's magnetic field. These
      organelles, called magnetosomes, consist of membrane-enclosed magnetite crystals
      that are thought to help to direct bacterial swimming towards growth-favouring
      microoxic zones at the bottom of natural waters. Questions in the study of
      magnetosome formation include understanding the factors governing the size and
      redox-controlled synthesis of the nano-sized magnetosomes and their assembly into
      a regular chain in order to achieve the maximum possible magnetic moment, against
      the physical tendency of magnetosome agglomeration. A deeper understanding of
      these mechanisms is expected from studying the genes present in the identified
      chromosomal 'magnetosome island', for which the connection with magnetosome
      synthesis has become evident. Here we use gene deletion in Magnetospirillum
      gryphiswaldense to show that magnetosome alignment is coupled to the presence of
      the mamJ gene product. MamJ is an acidic protein associated with a novel
      filamentous structure, as revealed by fluorescence microscopy and cryo-electron
      tomography. We suggest a mechanism in which MamJ interacts with the magnetosome
      surface as well as with a cytoskeleton-like structure. According to our
      hypothesis, magnetosome architecture represents one of the highest structural
      levels achieved in prokaryotic cells.

PMID- 16299496
TI  - Loading history determines the velocity of actin-network growth.
AB  - Directional polymerization of actin filaments in branched networks is one of the
      most powerful force-generating systems in eukaryotic cells. Growth of densely
      cross-linked actin networks drives cell crawling, intracellular transport of
      vesicles and organelles, and movement of intracellular pathogens such as Listeria
      monocytogenes. Using a modified atomic force microscope (AFM), we obtained force
      velocity (Fv) measurements of growing actin networks in vitro until network
      elongation ceased at the stall force. We found that the growth velocity of a
      branched actin network against increasing forces is load-independent over a wide
      range of forces before a convex decline to stall. Surprisingly, when force was
      decreased on a growing network, the velocity increased to a value greater than
      the previous velocity, such that two or more stable growth velocities can exist
      at a single load. These results demonstrate that a single Fv relationship does
      not capture the complete behaviour of this system, unlike other molecular motors
      in cells, because the growth velocity depends on loading history rather than
      solely on the instantaneous load.

PMID- 16299497
TI  - Prevention of early flowering by expression of FLOWERING LOCUS C requires
      methylation of histone H3 K36.
AB  - Flowering represents a crucial transition from a vegetative to a reproductive
      phase of the plant life cycle. Despite extensive studies, the molecular
      mechanisms controlling flowering remain elusive. Although the enzymes involved
      are unknown, methylation of histone H3 K9 and K27 correlates with repression of
      FLOWERING LOCUS C (FLC), an essential transcriptional repressor involved in
      flowering time control in Arabidopsis thaliana; in contrast, methylation of H3K4
      correlates with FLC activation. Here we show that loss-of-function of SET DOMAIN
      GROUP 8 (SDG 8), which encodes a homologue of the yeast SET2 histone
      methyltransferase, results in reduced dimethylation of histone H3K36,
      particularly in chromatin associated with the FLC promoter and the first intron,
      regions that contain essential cis-elements for transcription. sdg8 mutants
      display reduced FLC expression and flower early, establishing SDG8-mediated H3K36
      methylation as a novel epigenetic memory code required for FLC expression in
      preventing early flowering. This is the first demonstrated role of H3K36
      methylation in eukaryote development.

PMID- 16299498
TI  - A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex
      development.
AB  - Disrupted-In-Schizophrenia-1 (DISC1), originally identified at the breakpoint of
      a chromosomal translocation that is linked to a rare familial schizophrenia, has
      been genetically implicated in schizophrenia in other populations. Schizophrenia
      involves subtle cytoarchitectural abnormalities that arise during
      neurodevelopment, but the underlying molecular mechanisms are unclear. Here, we
      demonstrate that DISC1 is a component of the microtubule-associated dynein motor
      complex and is essential for maintaining the complex at the centrosome, hence
      contributing to normal microtubular dynamics. Carboxy-terminal-truncated mutant
      DISC1 (mutDISC1), which results from a chromosomal translocation, functions in a
      dominant-negative manner by redistributing wild-type DISC1 through self
      association and by dissociating the DISC1-dynein complex from the centrosome.
      Consequently, either depletion of endogenous DISC1 or expression of mutDISC1
      impairs neurite outgrowth in vitro and proper development of the cerebral cortex
      in vivo. These results indicate that DISC1 is involved in cerebral cortex
      development, and suggest that loss of DISC1 function may underlie
      neurodevelopmental dysfunction in schizophrenia.

PMID- 16299499
TI  - mPins modulates PSD-95 and SAP102 trafficking and influences NMDA receptor
      surface expression.
AB  - Appropriate trafficking and targeting of glutamate receptors (GluRs) to the
      postsynaptic density is crucial for synaptic function. We show that mPins
      (mammalian homologue of Drosophila melanogaster partner of inscuteable) interacts
      with SAP102 and PSD-95 (two PDZ proteins present in neurons), and functions in
      the formation of the NMDAR-MAGUK (N-methyl-D-aspartate receptor-membrane
      associated guanylate kinase) complex. mPins enhances trafficking of SAP102 and
      NMDARs to the plasma membrane in neurons. Expression of dominant-negative
      constructs and short-interfering RNA (siRNA)-mediated knockdown of mPins
      decreases SAP102 in dendrites and modifies surface expression of NMDARs. mPins
      changes the number and morphology of dendritic spines and these effects depend on
      its Galphai interaction domain, thus implicating G-protein signalling in the
      regulation of postsynaptic structure and trafficking of GluRs.

PMID- 16299500
TI  - Prior experience of rotation is not required for recognizing objects seen from
      different angles.
AB  - An object viewed from different angles can be recognized and distinguished from
      similar distractors after the viewer has had experience watching it rotate. It
      has been assumed that as an observer watches the rotation, separate
      representations of individual views become associated with one another. However,
      we show here that once monkeys learned to discriminate individual views of
      objects, they were able to recognize objects across rotations up to 60 degrees ,
      even though there had been no opportunity to learn the association between
      different views. Our results suggest that object recognition across small or
      medium changes in viewing angle depends on features common to similar views of
      objects.

PMID- 16299501
TI  - Conditional dendritic spike propagation following distal synaptic activation of
      hippocampal CA1 pyramidal neurons.
AB  - The perforant-path projection to the hippocampus forms synapses in the apical
      tuft of CA1 pyramidal neurons. We used computer modeling to examine the function
      of these distal synaptic inputs, which led to three predictions that we confirmed
      in experiments using rat hippocampal slices. First, activation of CA1 neurons by
      the perforant path is limited, a result of the long distance between these inputs
      and the soma. Second, activation of CA1 neurons by the perforant path depends on
      the generation of dendritic spikes. Third, the forward propagation of these
      spikes is unreliable, but can be facilitated by modest activation of Schaffer
      collateral synapses in the upper apical dendrites. This 'gating' of dendritic
      spike propagation may be an important activation mode of CA1 pyramidal neurons,
      and its modulation by neurotransmitters or long-term, activity-dependent
      plasticity may be an important feature of dendritic integration during mnemonic
      processing in the hippocampus.

PMID- 16299502
TI  - NMDA receptors regulate developmental gap junction uncoupling via CREB signaling.
AB  - Signaling through gap junctions (electrical synapses) is important in the
      development of the mammalian central nervous system. Abundant between neurons
      during postnatal development, gap junction coupling subsequently decreases and
      remains low in the adult, confined to specific subsets of neurons. Here we report
      that developmental uncoupling of gap junctions in the rat hypothalamus in vivo
      and in vitro is associated with a decrease in connexin 36 (Cx36) protein
      expression. Both developmental gap junction uncoupling and Cx36 downregulation
      are prevented by the blockade of NMDA glutamate receptors, action potentials and
      the calcium-cyclic AMP response element binding protein (CREB), and are
      accelerated by CREB overexpression. Developmental gap junction uncoupling and
      Cx36 downregulation are not affected by blockade of non-NMDA glutamate receptors,
      and do not occur in hypothalamic neurons from NMDA receptor subunit 1 (NMDAR1)
      knockout mice. These results demonstrate that NMDA receptor activity contributes
      to the developmental uncoupling of gap junctions via CREB-dependent
      downregulation of Cx36.

PMID- 16299503
TI  - The prolactin-releasing peptide antagonizes the opioid system through its
      receptor GPR10.
AB  - Prolactin-releasing peptide (PrRP) and its receptor G protein-coupled receptor 10
      (GPR10) are expressed in brain areas involved in the processing of nociceptive
      signals. We investigated the role of this new neuropeptidergic system in GPR10
      knockout mice. These mice had higher nociceptive thresholds and stronger stress
      induced analgesia than wild-type mice, differences that were suppressed by
      naloxone treatment. In addition, potentiation of morphine-induced antinociception
      and reduction of morphine tolerance were observed in mutants.
      Intracerebroventricular administration of PrRP in wild-type mice promoted
      hyperalgesia and reversed morphine-induced antinociception. PrRP administration
      had no effect on GPR10-mutant mice, showing that its effects are mediated by
      GPR10. Anti-opioid effects of neuropeptide FF were found to require a functional
      PrRP-GPR10 system. Finally, GPR10 deficiency enhanced the acquisition of morphine
      induced conditioned place preference and decreased the severity of naloxone
      precipitated morphine withdrawal syndrome. Altogether, our data identify the PrRP
      GPR10 system as a new and potent negative modulator of the opioid system.

PMID- 16299504
TI  - K-ATP channels promote the differential degeneration of dopaminergic midbrain
      neurons.
AB  - The selective degeneration of dopaminergic (DA) midbrain neurons in the
      substantia nigra (SN) is a hallmark of Parkinson disease. DA neurons in the
      neighboring ventral tegmental area (VTA) are significantly less affected. The
      mechanisms for this differential vulnerability of DA neurons are unknown. We
      identified selective activation of ATP-sensitive potassium (K-ATP) channels as a
      potential mechanism. We show that in response to parkinsonism-inducing toxins,
      electrophysiological activity of SN DA neurons, but not VTA DA neurons, is lost
      owing to activation of K-ATP channels. This selective K-ATP channel activation is
      controlled by differences in mitochondrial uncoupling between SN and VTA DA
      neurons. Genetic inactivation of the K-ATP channel pore-forming subunit Kir6.2
      resulted in a selective rescue of SN but not VTA DA neurons in two
      mechanistically distinct mouse models of dopaminergic degeneration, the
      neurotoxicological 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model and
      the mutant weaver mouse. Thus, K-ATP channel activation has an unexpected role in
      promoting death of DA neurons in chronic disease.

PMID- 16299505
TI  - The aminopeptidase ERAAP shapes the peptide repertoire displayed by major
      histocompatibility complex class I molecules.
AB  - Major histocompatibility complex (MHC) class I molecules present thousands of
      peptides to allow CD8(+) T cells to detect abnormal intracellular proteins. The
      antigen-processing pathway for generating peptides begins in the cytoplasm, and
      the MHC molecules are loaded in the endoplasmic reticulum. However, the nature of
      peptide pool in the endoplasmic reticulum and the proteolytic events that occur
      in this compartment are unclear. We addressed these issues by generating mice
      lacking the endoplasmic reticulum aminopeptidase associated with antigen
      processing (ERAAP). We found that loss of ERAAP disrupted the generation of
      naturally processed peptides in the endoplasmic reticulum, decreased the
      stability of peptide-MHC class I complexes and diminished CD8(+) T cell
      responses. Thus, trimming of antigenic peptides by ERAAP in the endoplasmic
      reticulum is essential for the generation of the normal repertoire of processed
      peptides.

PMID- 16299506
TI  - Relationships between supercontraction and mechanical properties of spider silk.
AB  - Typical spider dragline silk tends to outperform other natural fibres and most
      man-made filaments. However, even small changes in spinning conditions can have
      large effects on the mechanical properties of a silk fibre as well as on its
      water uptake. Absorbed water leads to significant shrinkage in an unrestrained
      dragline fibre and reversibly converts the material into a rubber. This process
      is known as supercontraction and may be a functional adaptation for the silk's
      role in the spider's web. Supercontraction is thought to be controlled by
      specific motifs in the silk proteins and to be induced by the entropy-driven
      recoiling of molecular chains. In analogy, in man-made fibres thermal shrinkage
      induces changes in mechanical properties attributable to the entropy-driven
      disorientation of 'unfrozen' molecular chains (as in polyethylene terephthalate)
      or the 'broken' intermolecular hydrogen bonds (as in nylons). Here we show for
      Nephila major-ampullate silk how in a biological fibre the spinning conditions
      affect the interplay between shrinkage and mechanical characteristics. This
      interaction reveals design principles linking the exceptional properties of silk
      to its molecular orientation.

PMID- 16299507
TI  - Diffractive electron imaging of nanoparticles on a substrate.
AB  - The observation of the detailed atomic arrangement within nanostructures has
      previously required the use of an electron microscope for imaging. The
      development of diffractive (lensless) imaging in X-ray science and electron
      microscopy using ab initio phase retrieval provides a promising tool for
      nanostructural characterization. We show that it is possible experimentally to
      reconstruct the atomic-resolution complex image (exit-face wavefunction) of a
      small particle lying on a thin carbon substrate from its electron
      microdiffraction pattern alone. We use a modified iterative charge-flipping
      algorithm and an estimate of the complex substrate image is subtracted at each
      iteration. The diffraction pattern is recorded using a parallel beam with a
      diameter of approximately 50 nm, illuminating a gold nanoparticle of
      approximately 13.6 nm diameter. Prior knowledge of the boundary of the object is
      not required. The method has the advantage that the reconstructed exit-face
      wavefunction is free of the aberrations of the objective lens normally used in
      the microscope, whereas resolution is limited only by thermal vibration and
      noise.

PMID- 16299508
TI  - Optical gain and stimulated emission in periodic nanopatterned crystalline
      silicon.
AB  - Persistent efforts have been made to achieve efficient light emission from
      silicon in the hope of extending the reach of silicon technology into fully
      integrated optoelectronic circuits, meeting the needs for high-bandwidth
      intrachip and interchip connects. Enhanced light emission from silicon is known
      to be theoretically possible, enabled mostly through quantum-confinement effects.
      Furthermore, Raman-laser conversion was demonstrated in silicon waveguides. Here
      we report on optical gain and stimulated emission in uniaxially nanopatterned
      silicon-on-insulator using a nanopore array as an etching mask. In edge-emission
      measurements, we observed threshold behaviour, optical gain, longitudinal cavity
      modes and linewidth narrowing, along with a collimated far-field pattern, all
      indicative of amplification and stimulated emission. The sub-bandgap 1,278 nm
      emission peak is attributed to A-centre mediated phononless direct recombination
      between trapped electrons and free holes. The controlled nanoscale silicon
      engineering, combined with the low material loss in this sub-bandgap spectral
      range and the long electron lifetime in such A-type trapping centres, gives rise
      to the measured optical gain and stimulated emission and provides a new pathway
      to enhance light emission from silicon.

PMID- 16299509
TI  - Trapping and moving metal atoms with a six-leg molecule.
AB  - Putting to work a molecule able to collect and carry adatoms in a controlled way
      on a surface is a solution for fabricating atomic structures atom by atom.
      Investigations have shown that the interaction of an organic molecule with the
      surface of a metal can induce surface reconstruction down to the atomic scale. In
      this way, well-defined nanostructures such as chains of adatoms, atomic trenches
      and metal-ligand compounds have been formed. Moreover, the progress in
      manipulation techniques induced by a scanning tunnelling microscope (STM) has
      opened up the possibility of studying artificially built molecular-metal atomic
      scale structures, and allowed the atom-by-atom doping of a single C(60) molecule
      by picking up K atoms. The present work goes a step further and combines STM
      manipulation techniques with the ability of a molecule to assemble an atomic
      nanostructure. We present a well-designed six-leg single hexa-t-butyl
      hexaphenylbenzene (HB-HPB) molecule, which collects and carries up to six copper
      adatoms on a Cu(111) surface when manipulated with a STM tip. The 'HB-HPB-Cu
      atoms' complex can be further manipulated, bringing its Cu freight to a
      predetermined position on the surface where the metal atoms can finally be
      released.

PMID- 16299510
TI  - Light-induced gene transfer from packaged DNA enveloped in a dendrimeric
      photosensitizer.
AB  - The control of gene transfection in the body is a core issue in gene therapy.
      Photochemical internalization is a technology that allows light-induced delivery
      of DNA, drugs or other biological factors directly inside cells. Usually it
      requires that a photosensitizer be added to the drug-delivery system to
      photochemically destabilize the endosomal membrane. Here we present a system for
      in vivo DNA delivery in which these two components are assembled into one
      structure. This is a ternary complex composed of a core containing DNA packaged
      with cationic peptides and enveloped in the anionic dendrimer phthalocyanine,
      which provides the photosensitizing action. The ternary complex showed more than
      100-fold photochemical enhancement of transgene expression in vitro with reduced
      photocytotoxicity. In an animal experiment, subconjuctival injection of the
      ternary complex followed by laser irradiation resulted in transgene expression
      only in the laser-irradiated site. This work demonstrates a new biomedical
      application for dendrimers, and the first success in the photochemical
      internalization-mediated gene delivery in vivo.

PMID- 16299511
TI  - Insights into voltage-gated calcium channel regulation from the structure of the
      CaV1.2 IQ domain-Ca2+/calmodulin complex.
AB  - Changes in activity-dependent calcium flux through voltage-gated calcium channels
      (Ca(V)s) drive two self-regulatory calcium-dependent feedback processes that
      require interaction between Ca(2+)/calmodulin (Ca(2+)/CaM) and a Ca(V) channel
      consensus isoleucine-glutamine (IQ) motif: calcium-dependent inactivation (CDI)
      and calcium-dependent facilitation (CDF). Here, we report the high-resolution
      structure of the Ca(2+)/CaM-Ca(V)1.2 IQ domain complex. The IQ domain engages
      hydrophobic pockets in the N-terminal and C-terminal Ca(2+)/CaM lobes through
      sets of conserved 'aromatic anchors.' Ca(2+)/N lobe adopts two conformations that
      suggest inherent conformational plasticity at the Ca(2+)/N lobe-IQ domain
      interface. Titration calorimetry experiments reveal competition between the lobes
      for IQ domain sites. Electrophysiological examination of Ca(2+)/N lobe aromatic
      anchors uncovers their role in Ca(V)1.2 CDF. Together, our data suggest that
      Ca(V) subtype differences in CDI and CDF are tuned by changes in IQ domain
      anchoring positions and establish a framework for understanding CaM lobe-specific
      regulation of Ca(V)s.

PMID- 16299512
TI  - RNA-mediated interaction between the peptide-binding and GTPase domains of the
      signal recognition particle.
AB  - The signal recognition particle (SRP) targets nascent proteins to cellular
      membranes for insertion or secretion by recognizing polypeptides containing an N
      terminal signal sequence as they emerge from the ribosome. GTP-dependent binding
      of SRP to its receptor protein leads to controlled release of the nascent chain
      into a membrane-spanning translocon pore. Here we show that the association of
      the SRP with its receptor triggers a marked conformational change in the complex,
      localizing the SRP RNA and the adjacent signal peptide-binding site at the SRP
      receptor heterodimer interface. The orientation of the RNA suggests how peptide
      binding and GTP hydrolysis can be coupled through direct structural contact
      during cycles of SRP-directed protein translocation.

PMID- 16299513
TI  - Swc2 is a widely conserved H2AZ-binding module essential for ATP-dependent
      histone exchange.
AB  - The histone variant H2AZ is incorporated preferentially at specific locations in
      chromatin to modulate chromosome functions. In Saccharomyces cerevisiae,
      deposition of histone H2AZ is mediated by the multiprotein SWR1 complex, which
      catalyzes ATP-dependent exchange of nucleosomal histone H2A for H2AZ. Here, we
      define interactions between SWR1 components and H2AZ, revealing a link between
      the ATPase domain of Swr1 and three subunits required for the binding of H2AZ. We
      discovered that Swc2 binds directly to and is essential for transfer of H2AZ.
      Swc6 and Arp6 are necessary for the association of Swc2 and for nucleosome
      binding, whereas other subunits, Swc5 and Yaf9, are required for H2AZ transfer
      but neither H2AZ nor nucleosome binding. Finally, the C-terminal alpha-helix of
      H2AZ is crucial for its recognition by SWR1. These findings provide insight on
      the initial events of histone exchange.

PMID- 16299514
TI  - Structure and chromosomal DNA binding of the SWIRM domain.
AB  - The evolutionarily conserved Swi3p, Rsc8p and Moira (SWIRM) domain is found in
      many chromosomal proteins involved in chromatin modifications or remodeling. Here
      we report the three-dimensional solution structure of the SWIRM domain from the
      human transcriptional adaptor ADA2alpha. The structure reveals a five-helix
      bundle consisting of two helix-turn-helix motifs connected by a central long
      helix, reminiscent of the histone fold. Using structural and biochemical
      analyses, we showed that the SWIRM domains of human ADA2alpha and SMARC2 bind to
      double-stranded and nucleosomal DNA, and we identified amino acid residues
      required for this function. We demonstrated that the ADA2alpha SWIRM domain is
      colocalized with lysine-acetylated histone H3 in the cell nucleus and that it
      potentiates the ACF remodeling activity by enhancing accessibility of nucleosomal
      linker DNA bound to histone H1. These data suggest a functional role of the SWIRM
      domain in chromatin remodeling.

PMID- 16299515
TI  - Folding zones inside the ribosomal exit tunnel.
AB  - Helicity of membrane proteins can be manifested inside the ribosome tunnel, but
      the determinants of compact structure formation inside the tunnel are largely
      unexplored. Using an extended nascent peptide as a molecular tape measure of the
      ribosomal tunnel, we have previously demonstrated helix formation inside the
      tunnel. Here, we introduce a series of consecutive polyalanines into different
      regions of the tape measure to monitor the formation of compact structure in the
      nascent peptide. We find that the formation of compact structure of the
      polyalanine sequence depends on its location. Calculation of free energies for
      the equilibria between folded and unfolded nascent peptides in different regions
      of the tunnel shows that there are zones of secondary structure formation inside
      the ribosomal exit tunnel. These zones may have an active role in nascent-chain
      compaction.

PMID- 16299516
TI  - Concerted regulation of nuclear and cytoplasmic activities of SR proteins by AKT.
AB  - Serine/arginine-rich (SR) proteins are important regulators of mRNA splicing.
      Several postsplicing activities have been described for a subset of shuttling SR
      proteins, including regulation of mRNA export and translation. Using the
      fibronectin gene to study the links between signal-transduction pathways and SR
      protein activity, we show that growth factors not only modify the alternative
      splicing pattern of the fibronectin gene but also alter translation of reporter
      messenger RNAs in an SR protein-dependent fashion, providing two coregulated
      levels of isoform-specific amplification. These effects are inhibited by specific
      small interfering RNAs against SR proteins and are mediated by the AKT kinase,
      which elicits opposite effects to those evoked by overexpressing SR protein
      kinases Clk and SRPK. These results show how SR protein activity is modified in
      response to extracellular stimulation, leading to a concerted regulation of
      splicing and translation.

PMID- 16299517
TI  - A miniature yeast telomerase RNA functions in vivo and reconstitutes activity in
      vitro.
AB  - The ribonucleoprotein enzyme telomerase synthesizes DNA at the ends of
      chromosomes. Although the telomerase catalytic protein subunit (TERT) is well
      conserved, the RNA component is rapidly evolving in both size and sequence. Here,
      we reduce the 1,157-nucleotide (nt) Saccharomyces cerevisiae TLC1 RNA to a size
      smaller than the 451-nt human RNA while retaining function in vivo. We conclude
      that long protein-binding arms are not essential for the RNA to serve its
      scaffolding function. Although viable, cells expressing Mini-T have shortened
      telomeres and reduced fitness as compared to wild-type cells, suggesting why the
      larger RNA has evolved. Previous attempts to reconstitute telomerase activity in
      vitro using TLC1 and yeast TERT (Est2p) have been unsuccessful. We find that
      substitution of Mini-T for wild-type TLC1 in a reconstituted system yields robust
      activity, allowing the contributions of individual yeast telomerase components to
      be directly assessed.

PMID- 16299518
TI  - A conserved processing mechanism regulates the activity of transcription factors
      Cubitus interruptus and NF-kappaB.
AB  - The proteasome degrades some proteins, such as transcription factors Cubitus
      interruptus (Ci) and NF-kappaB, to generate biologically active protein
      fragments. Here we have identified and characterized the signals in the substrate
      proteins that cause this processing. The minimum signal consists of a simple
      sequence preceding a tightly folded domain in the direction of proteasome
      movement. The strength of the processing signal depends primarily on the
      complexity of the simple sequence rather than on amino acid identity, the
      resistance of the folded domain to unraveling by the proteasome and the spacing
      between the simple sequence and folded domain. We show that two unrelated
      transcription factors, Ci and NF-kappaB, use this mechanism to undergo partial
      degradation by the proteasome in vivo. These findings suggest that the mechanism
      is conserved evolutionarily and that processing signals may be widespread in
      regulatory proteins.

PMID- 16299519
TI  - Multivalent avimer proteins evolved by exon shuffling of a family of human
      receptor domains.
AB  - We have developed a class of binding proteins, called avimers, to overcome the
      limitations of antibodies and other immunoglobulin-based therapeutic proteins.
      Avimers are evolved from a large family of human extracellular receptor domains
      by in vitro exon shuffling and phage display, generating multidomain proteins
      with binding and inhibitory properties. Linking multiple independent binding
      domains creates avidity and results in improved affinity and specificity compared
      with conventional single-epitope binding proteins. Other potential advantages
      over immunoglobulin domains include simple and efficient production of
      multitarget-specific molecules in Escherichia coli, improved thermostability and
      resistance to proteases. Avimers with sub-nM affinities were obtained against
      five targets. An avimer that inhibits interleukin 6 with 0.8 pM IC50 in cell
      based assays is biologically active in two animal models.

PMID- 16299520
TI  - Artificial cell-cell communication in yeast Saccharomyces cerevisiae using
      signaling elements from Arabidopsis thaliana.
AB  - The construction of synthetic cell-cell communication networks can improve our
      quantitative understanding of naturally occurring signaling pathways and enhance
      our capabilities to engineer coordinated cellular behavior in cell populations.
      Towards accomplishing these goals in eukaryotes, we developed and analyzed two
      artificial cell-cell communication systems in yeast. We integrated Arabidopsis
      thaliana signal synthesis and receptor components with yeast endogenous protein
      phosphorylation elements and new response promoters. In the first system,
      engineered yeast 'sender' cells synthesize the plant hormone cytokinin, which
      diffuses into the environment and activates a hybrid exogenous/endogenous
      phosphorylation signaling pathway in nearby engineered yeast 'receiver' cells.
      For the second system, the sender network was integrated into the receivers under
      positive-feedback regulation, resulting in population density-dependent gene
      expression (that is, quorum sensing). The combined experimental work and
      mathematical modeling of the systems presented here can benefit various
      biotechnology applications for yeast and higher level eukaryotes, including
      fermentation processes, biomaterial fabrication and tissue engineering.

PMID- 16299525
TI  - Viruses: tools for tumor target discovery, and agents for oncolytic therapies -
      an introduction.

PMID- 16299526
TI  - Viruses - seeking and destroying the tumor program.
AB  - DNA viruses have enormous utility in cancer research, both as tools for tumor
      target discovery as well as agents for lytic cancer therapies. This is because
      there is a profound functional overlap between the DNA viral and tumor cell
      programs. DNA viruses encode proteins that elicit growth deregulation in infected
      cells similar to that engendered by mutations in tumor cells. Evolution has
      refined viral proteins to target the critical cellular hubs that regulate growth.
      Thus, viral proteins are discriminating biochemical probes that can be used to
      identify and characterize novel tumor targets. Moreover, the overlap between the
      DNA viral and tumor programs can also be exploited for the development of lytic
      cancer therapies. Discovering whether tumor cells selectively complement the
      replication of viral mutants can reveal novel oncolytic viral therapies, as well
      as unexpected tumor properties. For example, altered RNA export was recently
      uncovered as a novel tumor cell property that underlies ONYX-015 replication, a
      promising oncolytic adenoviral therapy. A perspective is provided on how
      adenovirus could be systematically exploited to map the requisite role, or indeed
      the redundancy, of cellular pathways that act in an integrated program to elicit
      pathological replication. This knowledge has important applications for the
      rational design of the next generation of oncolytic viruses, as well as the
      discovery of efficacious combination cancer therapies.

PMID- 16299527
TI  - Retroviral insertional mutagenesis: past, present and future.
AB  - Retroviral insertion mutagenesis screens in mice are powerful tools for efficient
      identification of oncogenic mutations in an in vivo setting. Many oncogenes
      identified in these screens have also been shown to play a causal role in the
      development of human cancers. Sequencing and annotation of the mouse genome,
      along with recent improvements in insertion site cloning has greatly facilitated
      identification of oncogenic events in retrovirus-induced tumours. In this review,
      we discuss the features of retroviral insertion mutagenesis screens, covering the
      mechanisms by which retroviral insertions mutate cellular genes, the practical
      aspects of insertion site cloning, the identification and analysis of common
      insertion sites, and finally we address the potential for use of somatic
      insertional mutagens in the study of nonhaematopoietic and nonmammary tumour
      types.

PMID- 16299528
TI  - Recent lessons in gene expression, cell cycle control, and cell biology from
      adenovirus.
AB  - Adenovirus continues to be an important model system for investigating basic
      aspects of cell biology. Interactions of several cellular proteins with E1A
      conserved regions (CR) 1 and 2, and inhibition of apoptosis by E1B proteins are
      required for oncogenic transformation. CR2 binds RB family members, de-repressing
      E2F transcription factors, thus activating genes required for cell cycling. E1B
      19K is a BCL2 homolog that binds and inactivates proapoptotic BAK and BAX. E1B
      55K binds p53, inhibiting its transcriptional activation function. In
      productively infected cells, E1B-55K and E4orf6 assemble a ubiquitin ligase with
      cellular proteins Elongins B and C, Cullin 5 and RBX1 that polyubiquitinates p53
      and one or more subunits of the MRN complex involved in DNA double-strand break
      repair, directing them to proteosomal degradation. E1A CR3 activates viral
      transcription by interacting with the MED23 Mediator subunit, stimulating
      preinitiation complex assembly on early viral promoters and probably also the
      rate at which they initiate transcription. The viral E1B-55K/E4orf6 ubiquitin
      ligase is also required for efficient viral late protein synthesis in many cell
      types, but the mechanism is not understood. E1A CR1 binds several chromatin
      modifying complexes, but how this contributes to stimulation of cellular DNA
      synthesis and transformation is not clear. E1A CR4 binds the CtBP corepressor,
      but the mechanism by which this modulates the frequency of transformation remains
      to be determined. Clearly, adenovirus has much left to teach us about fundamental
      cellular processes.

PMID- 16299529
TI  - Inactivating intracellular antiviral responses during adenovirus infection.
AB  - DNA viruses promote cell cycle progression, stimulate unscheduled DNA synthesis,
      and present the cell with an extraordinary amount of exogenous DNA. These insults
      elicit vigorous responses mediated by cellular factors that govern cellular
      homeostasis. To ensure productive infection, adenovirus has developed means to
      inactivate these intracellular antiviral responses. Among the challenges to the
      host cell is the viral DNA genome, which is viewed as DNA damage and elicits a
      cellular response to inhibit replication. Adenovirus therefore encodes proteins
      that dismantle the cellular DNA damage machinery. Studying virus-host
      interactions has yielded insights into the molecular functioning of fundamental
      cellular mechanisms. In addition, it has suggested ways that viral cytotoxicity
      can be exploited to offer a selective means of restricted growth in tumor cells
      as a therapy against cancer. In this review, we discuss aspects of the
      intracellular response that are unique to adenovirus infection and how adenoviral
      proteins produced from the early region E4 act to neutralize antiviral defenses,
      with a particular focus on DNA damage signaling.

PMID- 16299530
TI  - To replicate or not to replicate: achieving selective oncolytic virus replication
      in cancer cells through translational control.
AB  - To ensure that their mRNAs are translated and that the viral proteins necessary
      for assembling the next generation of infectious progeny are produced, viruses
      must effectively seize control of the translational machinery within their host
      cells. In many cases, the ability to productively engage host translational
      components can determine if a given cell type can support viral replication,
      illustrating the critical importance of this task in the viral life cycle.
      Failure to interface properly with the host translational apparatus can
      compromise the productive growth cycle, resulting in an abortive infection and
      radically restricting viral replication. Not only have viruses become facile at
      commandeering this machinery, they are also particularly adept at manipulating
      cellular translation control pathways for their own ends. In this review, the
      mechanisms by which numerous viruses manipulate host translational control
      circuits are discussed. Furthermore, particular attention is devoted to
      understanding how interfering with the ability of a virus to properly regulate
      translation in its host can be exploited to generate oncolytic strains that
      selectively replicate in cancer cells.

PMID- 16299531
TI  - VSV-tumor selective replication and protein translation.
AB  - The emergence of vesicular stomatatis virus (VSV) as a potent antitumor agent has
      made a dissection of the molecular determinants of host-cell permissiveness to
      this virus an important objective. Such insight would not only enable the
      intelligent design of future generations of recombinant VSV vectors to combat
      disease, but may also resolve general features of cellular transformation that
      may be exploited by this virus, and perhaps other oncolytic viruses. The
      defective pathways underlining the oncolytic activity of VSV remain to be fully
      determined but recent data indicates that flaws in innate immune responses,
      involving the interferon (IFN) system, may commonly occur in tumor cells and thus
      play a large role in facilitating oncolysis. Aside from the IFN system, however,
      it is almost certain that other key cellular pathways may be similarly defective
      and therefore cooperatively contribute towards mediating rapid oncolytic virus
      activity. Recent data have indicated that defects in cancer cell translational
      regulation could be one area that may be exploited by VSV. Certainly, all viruses
      require cellular protein synthesis pathways to facilitate their replication and
      many have devised numerous mechanisms to ensure that viral mRNAs become
      translated at the expense of the host. Using VSV as a model, this review will
      discuss some of the recent developments in the fields of innate immunity and
      translational regulation that may help explain mechanisms of viral oncolysis.

PMID- 16299532
TI  - Unshackling the links between reovirus oncolysis, Ras signaling, translational
      control and cancer.
AB  - Reovirus has an inherent preference for replicating in cells with dysregulated
      growth factor signaling cascades that comprise Ras activation. Precisely how
      reovirus exploits the host cell Ras pathway is unclear, but there is evidence
      suggesting that activated Ras signaling is important for efficient viral protein
      synthesis. Defining the molecular mechanism of reovirus oncolysis will shed light
      on reovirus replication and important aspects of cellular transformation, Ras
      signaling cascades and regulation of protein translation.

PMID- 16299533
TI  - SV40 large T antigen targets multiple cellular pathways to elicit cellular
      transformation.
AB  - DNA tumor viruses such as simian virus 40 (SV40) express dominant acting
      oncoproteins that exert their effects by associating with key cellular targets
      and altering the signaling pathways they govern. Thus, tumor viruses have proved
      to be invaluable aids in identifying proteins that participate in tumorigenesis,
      and in understanding the molecular basis for the transformed phenotype. The roles
      played by the SV40-encoded 708 amino-acid large T antigen (T antigen), and 174
      amino acid small T antigen (t antigen), in transformation have been examined
      extensively. These studies have firmly established that large T antigen's
      inhibition of the p53 and Rb-family of tumor suppressors and small T antigen's
      action on the pp2A phosphatase, are important for SV40-induced transformation. It
      is not yet clear if the Rb, p53 and pp2A proteins are the only targets through
      which SV40 transforms cells, or whether additional targets await discovery.
      Finally, expression of SV40 oncoproteins in transgenic mice results in effects
      ranging from hyperplasia to invasive carcinoma accompanied by metastasis,
      depending on the tissue in which they are expressed. Thus, the consequences of
      SV40 action on these targets depend on the cell type being studied. The
      identification of additional cellular targets important for transformation, and
      understanding the molecular basis for the cell type-specific action of the viral
      T antigens are two important areas through which SV40 will continue to contribute
      to our understanding of cancer.

PMID- 16299534
TI  - Involvement of PP2A in viral and cellular transformation.
AB  - Although the small DNA tumor virus SV40 (simian virus 40) fails to replicate in
      human cells, understanding how SV40 transforms human and murine cells has and
      continues to provide important insights into cancer initiation and maintenance.
      The early region of SV40 encodes two oncoproteins: the large T (LT) and small t
      (ST) antigens. SV40 LT contributes to murine and human cell transformation in
      part by inactivating the p53 and retinoblastoma protein tumor suppressor
      proteins. SV40 ST inhibits the activity of the protein phosphatase 2A (PP2A)
      family of serine-threonine phosphatases, and this interaction is required for
      SV40-mediated transformation of human cells. PP2A regulates multiple signaling
      pathways, suggesting many possible targets important for viral replication and
      cell transformation. Genetic manipulation of particular PP2A subunits has
      confirmed a role for specific complexes in transformation, and recent work
      implicates the perturbation of the phosphatidylinositol 3-kinase/Akt pathway and
      c-Myc stability in transformation by ST and PP2A. Mutations in PP2A subunits
      occur at low frequency in human tumors, suggesting that alterations of PP2A
      signaling play a role in both experimentally induced and spontaneously arising
      cancers. Unraveling the complexity of PP2A signaling will not only provide
      further insights into cancer development but may identify novel targets with
      promise for therapeutic manipulation.

PMID- 16299535
TI  - Modulation of cell function by small transmembrane proteins modeled on the bovine
      papillomavirus E5 protein.
AB  - Viruses have been subjected to intense study because of their medical importance
      and because they can provide fundamental insights into normal and pathological
      cellular processes. Indeed, much of our knowledge about basic cellular biology
      and biochemistry was acquired through the study of viruses, and some of
      medicine's greatest triumphs and challenges involve viruses. Since viruses have
      evolved to exploit important cell processes, they can provide tools and
      approaches to manipulate cell function. The small transmembrane E5 protein of
      bovine papillomavirus type 1 transforms cells by a unique mechanism involving
      ligand-independent activation of the platelet-derived growth factor beta
      receptor. Experiments summarized in this review suggest that it may be possible
      to use the E5 protein as a model to design an entirely new class of small,
      modular transmembrane proteins with novel biological activities.

PMID- 16299536
TI  - Development of transcriptionally regulated oncolytic adenoviruses.
AB  - Changes initiated at the cellular and systemic levels as a result of viral
      infection or neoplastic transformation share significant overlap. Therefore, the
      use of replicating viruses to treat tumors has long been postulated as a
      promising avenue for oncolytic therapy. Over the last 10 years, transcriptionally
      regulated adenoviruses have become a popular platform for the development of such
      oncolytic viruses. Placement of heterologous promoters in front of key adenoviral
      transcription units to achieve tumor- or tissue-specific viral replication is
      well documented. Various derivatives of this general strategy have led to
      considerable insight into its limitations, pitfalls, and potential. Although a
      general process can be described by which to develop transcriptionally regulated
      adenoviruses, it is apparent that few set rules can yet be defined as to what
      constitutes a safe, stable, and therapeutically effective vector. Clinical
      experiences to date suggest the short-term potential for this class of
      therapeutics lies in combination therapy regimens. Such lessons from the clinic
      suggest the next generation of transcriptionally regulated oncolytic adenoviruses
      take advantage of the ability of the platform to carry transgenes in order to
      deliver a multimodal therapy from a single agent. Beyond this 'arming' of the
      vectors lies the detargeting, retargeting, and coating of adenoviruses to improve
      the delivery of the agent to the treatment site(s). As a therapeutic platform,
      transcriptionally regulated adenoviruses are at an early stage of development
      with considerable opportunities for advancement.

PMID- 16299537
TI  - Oncolytic adenoviruses - selective retargeting to tumor cells.
AB  - Virotherapy is an approach for the treatment of cancer, in which the replicating
      virus itself is the anticancer agent. Virotherapy exploits the lytic property of
      virus replication to kill tumor cells. As this approach relies on viral
      replication, the virus can self-amplify and spread in the tumor from an initial
      infection of only a few cells. The success of this approach is fundamentally
      based on the ability to deliver the replication-competent viral genome to target
      cells with a requisite level of efficiency. With virotherapy, while a number of
      transcriptional retargeting strategies have been utilized to restrict viral
      replication to tumor cells, this review will focus primarily on transductional
      retargeting strategies, whereby oncolytic viruses can be designed to selectively
      infect tumor cells. Using the adenoviral vector paradigm, there are three broad
      strategies useful for viral retargeting. One strategy uses heterologous
      retargeting ligands that are bispecific in that they bind both to the viral
      vector as well as to a cell surface target. A second strategy uses genetically
      modified viral vectors in which a cellular retargeting ligand is incorporated. A
      third strategy involves the construction of chimeric recombinant vectors, in
      which a capsid protein from one virus is exchanged for that of another. These
      transductional retargeting strategies have the potential for reducing deleterious
      side effects, and increasing the therapeutic index of virotherapeutic agents.

PMID- 16299538
TI  - Meeting product development challenges in manufacturing clinical grade oncolytic
      adenoviruses.
AB  - Oncolytic adenoviruses have been considered for use as anticancer therapy for
      decades, and numerous means of conferring tumor selectivity have been developed.
      As with any new therapy, the trip from the laboratory bench to the clinic has
      revealed a number of significant development hurdles. Viral therapies are subject
      to specific regulations and must meet a variety of well-defined criteria for
      purity, potency, stability, and product characterization prior to their use in
      the clinic. Published regulatory guidelines, although developed specifically for
      biotechnology-derived products, are applicable to the production of oncolytic
      adenoviruses and other cell-based products, and they should be consulted early
      during development. Most importantly, both the manufacturing process and the
      development of characterization and release assays should be science-driven, use
      the best available science and technology, and must consider the unique nature of
      the product: a living, and mutatable, virus. Potentially significant impacts on
      product quality and safety stem from the possibility of genetic instability
      related to over-engineering the viruses (as evidenced by their recombination
      and/or occasional reversion to wild-type virus during manufacturing). This report
      provides examples of some of the critical components affecting the development
      and production of clinical grade material and summarizes the significant progress
      made in recent years.

PMID- 16299539
TI  - Oncolytic viral therapies - the clinical experience.
AB  - It has been 9 years since the beginning of the first clinical trial in which an
      oncolytic virus was administered to cancer patients. Since then, oncolytic
      viruses from five different species have been taken to phase I and II clinical
      trials in over 300 cancer patients. While additional studies will be required to
      ascertain if the efficacy of any of these agents is high enough to warrant adding
      them to the existing therapeutic regimen, it has been reassuring that DNA viruses
      engineered to achieve tumor selectivity and RNA viruses with relative inherent
      natural tumor selectivity have proven reasonably safe at the wide range of doses
      that were tested. Here, we review the biology and clinical results of these five
      species of viruses and discuss lessons learned and challenges for the future.

PMID- 16299540
TI  - Future prospects for oncolytic therapy.
AB  - Viruses have been engineered to replicate selectively in cancer cells, based on a
      number of innovative principles. Several of these viruses have entered clinical
      trials and have proven relatively safe, and have shown evidence of efficacy.
      However, further research is required to enable these agents to function
      systemically. This might involve attempts to suppress immune responses to virus
      antigens, and re-targeting of viruses to favor tumor infection and increased
      potency. When these barriers are overcome, oncolytic viruses could enter the
      mainstream of clinical oncology.

PMID- 16299541
TI  - Decision-making in adult thalassemia patients undergoing unrelated bone marrow
      transplantation: quality of life, communication and ethical issues.
AB  - Bone marrow transplantation (BMT) represents a potentially curative treatment of
      thalassemia. For patients without an HLA-identical sibling donor, recourse to an
      unrelated donor is a practicable option but the candidates and their families are
      faced with a difficult decision. They can either choose to continue the
      supportive therapy, with no chance of definitive cure, or they accept the
      mortality risk of BMT in the hope of obtaining a definitive resolution of the
      disease. We investigated the communication strategies and the post
      transplantation quality of life (QoL) in 19 adult thalassemia patients surviving
      after an unrelated donor BMT. The patients were given two questionnaires: a
      questionnaire to evaluate pre-transplantation communication factors and the EORTC
      QLQ-C30 questionnaire to assess global QoL. All patients were satisfied with the
      communication modalities employed by the physicians. The global post
      transplantation QoL in our patient cohort was found to be good. The approach used
      in this study may offer a contribution to understanding the decision-making
      process leading to the choice of a treatment with a high mortality risk for a
      chronic, non-malignant disease. Finally, some ethical issues of this therapeutic
      approach are briefly addressed.

PMID- 16299542
TI  - Successful autologous peripheral blood stem cell harvest and transplant in a
      patient with cold agglutinins.

PMID- 16299543
TI  - NK026680, a novel compound suppressive of dendritic cell function, ameliorates
      mortality in acute lethal graft-versus-host reaction in mice.
AB  - A role for dendritic cells (DCs) has been emphasized in the onset of acute graft
      versus-host disease (GVHD). We have made efforts to develop a new strategy for
      suppression of DC functions with a chemical compound in the treatment of acute
      GVHD. We here describe the immunological characterization of the new chemical
      compound NK026680. It was found that NK026680 significantly suppressed (1)
      expression of CD83, CD86, and major histocompatibility complex (MHC) class I and
      II antigens on human monocyte-derived DCs, (2) excretion of interleukin-12p40 on
      activation of monocyte-derived DCs, (3) allogeneic responses of human and mouse T
      cells and (4) mortality in mice with acute GVHD evoked across MHC class I or II.
      The beneficial effect of NK026680 administered orally was without any
      recognizable adverse effects. Early intervention in acute GVHD was required for
      this effect, indicating that an early event in acute GVHD is a critical target of
      NK026680. We propose the use of NK026680 as a prophylactic for acute GVHD.

PMID- 16299544
TI  - Randomized clinical trials for hematopoietic stem cell transplantation: lessons
      to be learned from the European experience.
AB  - We evaluated the number and characteristics of randomized controlled trials
      (RCTs) addressing hematopoietic stem cell transplantation (HSCT) for patients
      with hematological malignancies, comparing the productivity of US and Europe. A
      MEDLINE search was conducted to identify all published RCTs for the management of
      adult patients with hematological malignancies from January 1992 to December
      2003. Eighty-three of the 306 trials identified included HSCT as one of the
      treatment arms. The US produced 25, Europe 54, and all other countries four. Four
      European countries, France, Italy, Germany, and UK (FIGU), produced 32 out of the
      54 European studies. Significant differences emerged when focus of the study and
      accrual numbers were analyzed. Trials comparing HSCT to standard dose therapy
      represented 34.9% of the 83 trials and 59.4% of FIGU trials, but only 4% of US
      studies (P = 0.001). US trials accrued a mean of 110.2 patients per study, as
      compared to 222.6 in FIGU studies (P = 0.006) and 205.3 when all non-US countries
      are considered (P = 0.01). Our conclusions are that US transplant RCT have
      focused on issues other than the comparison of HSCT to standard therapies. There
      is serious paucity of US trials defining the role of HSCT in the management of
      hematological malignancies.

PMID- 16299545
TI  - Autologous stem cell transplantation for therapy-related acute myeloid leukemia
      and myelodysplastic syndrome.
AB  - We report the results of 65 patients with treatment-related myelodysplastic
      syndrome (MDS)/acute myelogenous leukemia (AML) who were transplanted from an
      autograft and reported to the EBMT. The median age was 39 years (range, 3-69),
      and stem cell source was bone marrow (n = 31), or peripheral blood progenitor
      cells (n = 30), or the combination of both (n = 4). The primary disease was solid
      tumors (n = 37), Hodgkin's disease (n = 13), non-Hodgkin's lymphoma (n = 10),
      acute lymphoblastic leukemia (n = 2) or myeloproliferative syndromes (n = 3). The
      types of MDS were as follows: RAEB (n = 1; 2%), RAEB-t (n = 3; 5%), or AML (n =
      56; 87%). The median time between diagnosis and transplantation was 5 months
      (range, 3-86). The Kaplan-Meier estimates of the probability of 3-year overall
      and disease-free survival were 35% (95% CI: 21-49%) and 32% (95% CI: 18-45%),
      respectively. The median leukocyte engraftment was faster after transplantation
      with peripheral blood stem cells than with bone marrow: 12 (range, 9-26) vs 29
      (range, 11-67) days (P<0.001). The cumulative incidence of relapse was 58% (95%
      CI: 44-72%) and of treatment-related mortality 12% (95% CI: 6-38%). Lower relapse
      rate was seen in patients transplanted in first complete remission (CR1 vs non
      CR1: 3 years: 48 vs 89%; P = 0.05). Furthermore, age beyond 40 years resulted in
      a higher treatment-related mortality (47 vs 7%; P = 0.01). In a multivariate
      analysis, transplantation in CR1 age as well as their interaction influenced
      overall survival significantly. Autologous transplantation may cure a substantial
      number of patients with treatment-related MDS/AML, especially if they are in CR1
      and of younger age.

PMID- 16299546
TI  - Evaluation of the effect of transplant-related factors and tissue injury on donor
      derived hepatocyte and gastrointestinal epithelial cell repopulation following
      hematopoietic cell transplantation.
AB  - The aim of this study was to detect donor-derived hepatocytes and
      gastrointestinal epithelial cells in recipients of sex-mismatched allogeneic
      hematopoietic cell transplants, and to assess the effect of tissue injury on the
      extent of the repopulation. A total of 29 paraffin-embedded biopsy samples were
      reviewed. Double labeling by immunohistochemistry and fluorescence in situ
      hybridization was performed. Eighty-nine percent of sex-mismatched samples with
      histologic evidence of injury demonstrated the presence of donor-derived
      hepatocytes and gastrointestinal epithelial cells (mean 2.4%). None of the
      hepatocytes and gastrointestinal epithelial cells in samples obtained from female
      recipients with female donors showed a Y chromosome signal. The proportion of
      donor-derived hepatocyte and gastrointestinal epithelial cells in samples with
      severe graft-versus-host disease was greater than that of samples with
      mild/moderate graft-versus-host disease (P = 0.09). No relationship between the
      source of stem cells and the population rate was detected (P > 0.05). We conclude
      that some recipient hepatocytes and gastrointestinal tract epithelial cells are
      replaced by donor-derived cells during tissue injury. The severity of tissue
      injury seems to influence on the extent of this repopulation.

PMID- 16299547
TI  - Study of the mechanisms involved in the vasorelaxation induced by (-)
      epigallocatechin-3-gallate in rat aorta.
AB  - This study investigated several mechanisms involved in the vasorelaxant effects
      of (-)-epigallocatechin-3-gallate (EGCG). EGCG (1 microM-1 mM) concentration
      dependently relaxed, after a transient increase in tension, contractions induced
      by noradrenaline (NA, 1 microM), high extracellular KCl (60 mM), or phorbol 12
      myristate 13-acetate (PMA, 1 microM) in intact rat aortic rings. In a Ca2+ -free
      solution, EGCG (1 microM-1 mM) relaxed 1 microM PMA-induced contractions, without
      previous transient contraction. However, EGCG (1 microM-1 mM) did not affect the
      1 microM okadaic acid-induced contractions. Removal of endothelium and/or
      pretreatment with glibenclamide (10 microM), tetraethylammonium (2 mM) or
      charybdotoxin (100 nM) plus apamin (500 nM) did not modify the vasorelaxant
      effects of EGCG. In addition, EGCG noncompetitively antagonized the contractions
      induced by NA (in 1.5 mM Ca2+ -containing solution) and Ca2+ (in depolarizing
      Ca2+ -free high KCl 60 mM solution). In rat aortic smooth muscle cells (RASMC),
      EGCG (100 microM) reduced increases in cytosolic free Ca2+ concentration
      ([Ca2+]i) induced by angiotensin II (ANG II, 100 nM) and KCl (60 mM) in 1.5 mM
      CaCl2 -containing solution and by ANG II (100 nM) in the absence of extracellular
      Ca2+. In RASMC, EGCG (100 microM) did not modify basal generation of cAMP or
      cGMP, but significantly reversed the inhibitory effects of NA (1 microM) and high
      KCl (60 mM) on cAMP and cGMP production. EGCG inhibited the enzymatic activity of
      all the cyclic nucleotide PDE isoenzymes present in vascular tissue, being more
      effective on PDE2 (IC50 approximately 17) and on PDE1 (IC50 approximately 25).
      Our results suggest that the vasorelaxant effects of EGCG in rat aorta are
      mediated, at least in part, by an inhibition of PDE activity, and the subsequent
      increase in cyclic nucleotide levels in RASMC, which, in turn, can reduce agonist
      or high KCl concentration-induced increases in [Ca2+]i.

PMID- 16299548
TI  - Inflammatory events in a vascular remodeling model induced by surgical injury to
      the rat carotid artery.
AB  - 1.--The aim of our study was to gain insight into the molecular and cellular
      mechanisms of the inflammatory response to arterial injury in a rat experimental
      model. 2.--Rats (five for each experimental time) were subjected to brief
      clamping and longitudinal incision of a carotid artery and monitored for 30 days.
      Subsequently, Nuclear Factor-kappaB (NF-kappaB) expression was measured by
      electrophoretic mobility shift assay. Heat shock protein (HSP) 27, HSP47 and
      HSP70 were evaluated by Western blot. Morphological changes of the vessel wall
      were investigated by light and electron microscopy. 3.--In injured rat carotid
      artery NF-kappaB activity started immediately upon injury, and peaked between 2
      and 3 weeks later. Western blot showed a significant increase of HSP47 and HSP70
      7 days after injury. At 2 weeks postinjury, HSP27 expression peaked. Light
      microscopy showed a neointima formation, discontinuity of the media layer and a
      rich infiltrate. Among infiltrating cells electron microscopy identified
      dendritic-like cells in contact with lymphocytes. 4.--Our model of surgical
      injury induces a significant inflammatory process characterized by enhanced NF
      kappaB activity and HSPs hyperexpression. Dendritic-like cells were for the first
      time identified as a novel component of tissue repair consequent to acute
      arterial injury.

PMID- 16299549
TI  - Blood-brain equilibration kinetics of levo-alpha-acetyl-methadol using a
      chronically instrumented sheep preparation.
AB  - 1.--The delayed onset and long duration of action of the opioid agonist levo
      alpha-acetyl-methadol (LAAM) has been attributed to the formation of active
      metabolites. However, at present, little is known about the time course of blood
      brain equilibration of LAAM itself. 2.--The cerebral kinetics of LAAM were
      quantified using physiologically based kinetic models and a conscious chronically
      instrumented sheep preparation. Seven sheep were administered 4 min intravenous
      infusions of 30 mg LAAM. Concentrations of LAAM and N-demethylated metabolites
      (nor-LAAM and di-nor-LAAM) in whole blood (0-75 min) were measured using a
      validated HPLC assay. 3.--LAAM did not alter cerebral blood flow, mean arterial
      pressure or cause significant respiratory depression. Cardiac output was similar
      to baseline at 4 min, but decreased by 30% at 10 min and remained at this level
      for the duration of the 75 min study period. 4.--Cerebral kinetics were best
      described by a membrane-limited model, with a relatively slow blood-brain tissue
      equilibration half-life of 22 min due to intermediate permeability (56 ml min(
      1)) and a large cerebral distribution volume (724 ml). 5.--In conclusion,
      pharmacokinetic-pharmacodynamic modelling of LAAM should account for the large
      equilibration delay between brain and blood caused by slow equilibration
      kinetics. This may account for some of the delay in onset of effect previously
      attributed to the delayed appearance of active metabolites in blood.

PMID- 16299550
TI  - Bv8, the amphibian homologue of the mammalian prokineticins, induces a
      proinflammatory phenotype of mouse macrophages.
AB  - 1.--The small protein Bv8, isolated from the amphibian skin, belongs to a novel
      family of secreted proteins linked to several biological effects. We describe the
      expression of Bv8/prokineticins and their receptors in mouse macrophages, and
      characterize their proinflammatory activities. 2.--The rodent analogue of Bv8,
      prokineticin-2, is expressed by macrophages, as well as its G-protein-coupled
      receptor prokineticin receptor (PKR-1 and PKR-2). PKR-1 is expressed more
      abundantly. 3.-- Bv8 induces potent chemotaxis of macrophages at concentrations
      as low as 10(-12) M. 4.-- It stimulates lipopolysaccharide-induced production of
      the proinflammatory cytokines IL-1 and IL-12, reducing that of the anti
      inflammatory cytokine IL-10. The effects are observed starting at the very low
      concentration of 10(-11) M. 5.--Effects on chemotaxis and cytokine are not
      pertussis-toxin sensitive, but are completely prevented by addition of the
      phospholipase inhibitor U73122, suggesting a G(q) protein is involved in the Bv8
      induced effects. 6.--Studies in PKR-1 knockout mice indicate that all the
      activities exerted by Bv8 on macrophages are mediated by the PKR-1 receptor. 7.-
      In conclusion, Bv8 appears to be able to induce the macrophage to migrate and to
      acquire a proinflammatory phenotype.

PMID- 16299551
TI  - Signaling mechanism of thrombin-induced gingival fibroblast-populated collagen
      gel contraction.
AB  - 1.--Thrombin is activated during gingival tissue injury and inflammation.
      Thrombin (platelet)-rich plasma has been used for periodontal regeneration with
      success. Thrombin and other bacterial proteases also affect the functions of
      adjacent periodontal cells via stimulation of protease-activated receptors
      (PARs). 2.--We noted that thrombin (0.1-2 U ml(-1)), human, and frog PAR-1
      agonist peptide (20-240 microM) induced the gingival fibroblast (GF)-populated
      collagen gel contraction within 2 h of exposure. However, PAR-2, PAR-3, and PAR-4
      agonist peptide (20-240 microM) showed little effect on collagen gel contraction.
      U73122 (phospholipase C inhibitor) and 2-APB (IP3 antagonist) were effective in
      inhibition of GF contraction. 3.--Thrombin-induced GF contraction was inhibited
      by 5 mM EGTA (an extracellular calcium chelator) and verapamil (an L-type calcium
      channel blocker). In addition, W7 (10 and 25 microM, a calcium/calmodulin (CaM)
      inhibitor), ML-7 (50 microM, myosin light chain kinase (MLCK) inhibitor), and
      HA1077 (100 microM, Rho kinase inhibitor) completely inhibited the thrombin
      induced collagen gel contraction. Thrombin also induced the phosphorylation of
      ERK1/ERK2 and elevated the Rho-GTP levels in GF. 4.--However, U0126 only
      partially inhibited the thrombin-induced GF contraction. Similarly, wortmannin
      (100 nM), LY294002 (20 microM) (two PI3K inhibitor) and genistein also showed
      partial inhibition. Moreover, NAC was not able to suppress the GF contraction, as
      supported by the slight decrease in reactive oxygen species production in GF by
      thrombin. 5.--Thrombin also stimulated metalloproteinase-2 (MMP-2) and MMP-3
      production in GF. But addition of GM6001 or 1,10-phenanthroline, two MMP
      inhibitors, could not inhibit the thrombin-induced GF contraction. 6.--These
      results indicate that thrombin is crucial in the periodontal inflammation and
      wound healing by promoting GF contraction. This event is mainly mediated via PAR
      1 activation, PLC activation, extracellular calcium influx via L-type calcium
      channel, and the calcium/CaM-MLCK and Rho kinase activation pathway.

PMID- 16299552
TI  - [32P]2-iodo-N6-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate
      ([32P]MRS2500), a novel radioligand for quantification of native P2Y1 receptors.
AB  - Analysis of the P2Y family of nucleotide-activated G-protein-coupled receptors
      has been compromised by the lack of selective high-affinity, high-specific
      radioactivity radioligands. We have pursued quantification of the P2Y1 receptor
      through the development of a series of selective P2Y1 receptor antagonists.
      Recently, we synthesized 2-iodo-N6-methyl-(N)-methanocarba-2'-deoxyadenosine
      3',5'-bisphosphate (MRS2500), a selective, competitive antagonist that exhibits a
      Ki of 0.8 nM in competition-binding assays with [3H]MRS2279. A 3'-monophosphate
      precursor molecule, MRS2608, was radiolabeled at the 5' position with 32P using
      polynucleotide kinase and [gamma32P]ATP to yield [32P]MRS2500. [32P]MRS2500 bound
      selectively to Sf9 insect cell membranes expressing the human P2Y1 receptor (Sf9
      P2Y1), but did not detectably bind membranes expressing other P2Y receptors. P2Y1
      receptor binding to [32P]MRS2500 was saturable with a KD of 1.2 nM. Agonists and
      antagonists of the P2Y1 receptor inhibited [32P]MRS2500 binding in Sf9-P2Y1
      membranes with values in agreement with those observed in functional assays of
      the P2Y1 receptor. A high-affinity binding site for [32P]MRS2500 (KD=0.33 nM) was
      identified in rat brain, which exhibited the pharmacological selectivity of the
      P2Y1 receptor. Distribution of this binding site varied among rat tissues, with
      the highest amount of binding appearing in lung, liver, and brain. Among brain
      regions, distribution of the [32P]MRS2500 binding site varied by six-fold, with
      the highest and lowest amounts of sites detected in cerebellum and cortex,
      respectively. Taken together, these data illustrate the synthesis and
      characterization of a novel P2Y1 receptor radioligand and its utility for
      examining P2Y1 receptor expression in native mammalian tissues.

PMID- 16299555
TI  - [Explosive distinctions].

PMID- 16299554
TI  - Cilnidipine, a slow-acting Ca2+ channel blocker, induces relaxation in porcine
      coronary artery: role of endothelial nitric oxide and [Ca2+]i.
AB  - Cilnidipine is a dual blocker of L-type voltage-gated Ca(2+) channels in vascular
      smooth muscle and N-type Ca(2+) channels in sympathetic nerve terminals that
      supply blood vessels. However, the clinical benefits of cilnidipine and
      underlying mechanisms are incompletely understood. This study was designed to
      compare the time course of relaxant responses to cilnidipine and nifedipine, and
      to examine the role of endothelial NO and [Ca(2+)](i) in the vasorelaxation.
      Porcine left circumflex coronary arteries were isolated and isometric tension was
      measured with Grass force transducers. Endothelial [Ca(2+)](i) in intact arteries
      was determined by a calcium fluorescence imaging technique. The free radical
      scavenging capacity was also assayed. Cilnidipine and nifedipine induced
      concentration-dependent relaxations in high KCl-precontracted artery rings, while
      the former-induced relaxation was slower as compared to the latter. Treatment
      with L-NAME or ODQ reduced relaxations to cilnidipine or nifedipine to the same
      extent as in rings without endothelium. Indomethacin or omega-conotoxin had no
      effects. L-Arginine antagonized the effect of L-NAME on cilnidipine-induced
      relaxations. Cilnidipine did not affect sodium nitroprusside-induced relaxation
      in rings with and without endothelium. Cilnidipine and nifedipine caused
      extracellular Ca(2+)-dependent increases in endothelial [Ca(2+)](i) in intact
      arteries and cilnidipine's action had a slower onset, similar to that of
      cilnidipine-induced relaxation. Neither cilnidipine nor nifedipine exhibited a
      free radical scavenging property. The present results demonstrate that
      cilnidipine can produce endothelium-dependent relaxation in porcine coronary
      arteries in vitro in addition to blocking Ca(2+) channels. Like short-acting
      nifedipine, cilnidipine-dependent relaxation, albeit to a slower onset, is partly
      mediated by endothelial NO but not by prostacyclin. The increased release or
      bioavailability of NO may causally result from elevated endothelial [Ca(2+)](i)
      in arteries. The Ca(2+) channel-independent effect suggests the usefulness of
      cilnidipine in the treatment of cardiovascular diseases associated with
      diminished NO release, such as atherosclerosis.

PMID- 16299553
TI  - The immunomodulator FTY720 and its phosphorylated derivative activate the Smad
      signalling cascade and upregulate connective tissue growth factor and collagen
      type IV expression in renal mesangial cells.
AB  - 1.--The immunomodulating agent FTY720 is a substrate for the sphingosine kinase
      and the phosphorylated form is able to bind to sphingosine 1-phosphate (S1P)
      receptors. In this study, we show that exposure of renal mesangial cells to
      phospho-FTY720 leads to a rapid and transient activation of several protein
      kinase cascades, including the mitogen- and stress-activated protein kinases. The
      nonphosphorylated FTY720 also increased MAPK phosphorylation, but with a reduced
      potency and a more delayed time course. In addition, phospho-FTY720 and FTY720
      are able to increase phosphorylation of Smad proteins which are classical members
      of the transforming growth factor-beta (TGF-beta) signalling device, thus
      suggesting a crosstalk between FTY720 and TGF-beta signalling. 2.--Pretreatment
      with the S1P(3) receptor antagonist suramin inhibits FTY720 and phospho-FTY720
      induced Smad phosphorylation, whereas pertussis toxin pretreatment, which blocks
      G(i/0) proteins, has no effect on Smad phosphorylation. 3.--Since TGF-beta is a
      potent profibrotic cytokine in mesangial cells and upregulates the connective
      tissue growth factor (CTGF) and collagen as important hallmarks in the fibrotic
      sequelae, we investigated whether FTY720 and phospho-FTY720 are able to mimic
      these effects of TGF-beta. Indeed, FTY720 and phospho-FTY720 markedly upregulate
      CTGF and collagen type IV protein expressions. In addition, the tissue inhibitor
      of metalloproteinase-1 is transcriptionally activated by FTY720, whereas cytokine
      induced matrix metalloproteinase-9 is down-regulated by FTY720. 4.--Depletion of
      the TGF-beta receptor type II by the siRNA transfection technique blocks not only
      Smad phosphorylation but also CTGF upregulation. Similarly, Smad-4 depletion by
      siRNA transfection also abrogates CTGF upregulation induced by FTY720 and phospho
      FTY720. 5.--In summary, our data show that FTY720 and phospho-FTY720 not only
      activate the Smad signalling cascade in mesangial cells, but also upregulate the
      expression of CTGF and collagen. These findings suggest that FTY720 may have
      additional effects besides the established immunomodulatory action and,
      importantly, a profibrotic activity has to be considered in future experimental
      approaches.

PMID- 16299556
TI  - [All-powerful or powerless physician?].

PMID- 16299557
TI  - [Is inequality dangerous for health?].

PMID- 16299558
TI  - [Skewed income distribution and geographical mortality differences].
AB  - BACKGROUND: A prominent theme in current health research is whether large income
      inequality in a society in itself has negative consequences for population
      health, in addition to the effects of individual risk factors. The present study
      investigates whether mortality in Norway during the 1990s was higher in
      geographical regions with particularly skewed income distributions. MATERIAL AND
      METHODS: Register data for all inhabitants aged 25-66 in Norway in 1992 were used
      (N = approx. 2.2 millions), including information about deaths 1993-99. Norwegian
      municipalities were grouped into 23 regions. Gini coefficients indicating the
      degree of inequality in the income distribution were calculated for each region.
      Deaths 1993-99 were analysed by means of multiple logistic regression. RESULTS:
      Odds ratios for deaths 1993-99 were strongly influenced by well-known individual
      risk factors such as sex, age, marital status, educational level, personal
      income, and disability. In addition, odds ratios for death were significantly
      associated with the regions' gini coefficients when adjustments were made for
      average income level in the regions. This effect of income inequality was
      pronounced for people with low education, but almost absent among those with
      higher education. Moreover, the income inequality effect was to some extent
      driven by special circumstances in Oslo, Norway's capital city, with its high
      mortality among the less educated and a particularly non-egalitarian income
      distribution. However, the pattern of higher mortality associated with higher
      levels of income inequality among the less educated was also observed in the 22
      regions outside Oslo. INTERPRETATION: We found a discernible, although not very
      strong, association between regional income inequality and mortality levels among
      the less educated. Several interpretations for this statistical tendency could be
      proposed; the social processes generating this tendency should be clarified
      further.

PMID- 16299560
TI  - [Overweight among eight and twelve-year-old children in Oslo in 2004].
AB  - BACKGROUND: Overweight among children is an increasing problem internationally.
      The body mass index of the parents and their children influences body mass index
      during adulthood and the probability of overweight and obesity. The aim of this
      survey was to obtain reliable data on weight and height for eight and twelve-year
      olds in Oslo. MATERIAL AND METHODS: School health nurses in Oslo took
      measurements of the children's weight and height. The survey includes 3453 eight
      year-olds and 3597 twelve-year-olds. RESULTS: The prevalence of overweight among
      eight-to-twelve-year-olds is 21%. There is a significant difference in the
      prevalence of overweight children between the local districts of Oslo. One in
      four of eight-year-old and one in five of twelve-year old girls are overweight.
      There is no significant difference between boys in different age groups.
      INTERPRETATION: The prevalence of overweight among eight to twelve-year-old
      children in Oslo is alarming. There are big differences between districts.

PMID- 16299559
TI  - [Diagnosing allergic reactions to ingested wheat in children].
AB  - BACKGROUND: Sensitisation to wheat demonstrated by specific IgE without clinical
      reactions to ingested wheat is common. Clinical allergy towards wheat may cause
      anaphylactic or mild reactions. Until now, oral challenge tests have been
      necessary for diagnosing severe reactions to ingested wheat. We wanted to
      distinguish between severe and mild reactions by using three different IgE tests
      against wheat. MATERIAL AND METHODS: 29 children with elevated levels of specific
      IgE against wheat (f4 test) were referred to our hospital for further diagnostic
      procedures. We performed specific IgE tests against different wheat components
      (f4, f79 and f98) and oral provocation tests. RESULTS: 10 children with severe
      clinical reactions had high levels at all three specific IgE tests and comparable
      levels between the tests. The 4 children with mild reactions showed varying
      values of IgE but very similar levels between the three different tests. 15
      children had negative provocation tests, varying levels of specific IgE, and less
      similar levels between the tests. INTERPRETATION: Available specific IgE tests
      are not useful in order to distinguish between severe, mild or no clinical
      reactions to ingested wheat. Oral challenge tests are still needed for correct
      diagnosis of severe wheat allergy.

PMID- 16299561
TI  - [Genetic causes of obesity].
AB  - BACKGROUND: Overweight and obesity represent an increasing health problem. Both
      genetic and environmental factors contribute to the development of obesity. This
      article summarises the genetic aspects of these conditions. MATERIAL AND METHODS:
      A literature search was conducted using PubMed and OMIM. Both original and review
      articles were included. RESULTS AND INTERPRETATION: The genetic influence on body
      weight is shown by twin and family studies. Environmental changes in recent
      decades have promoted the development of obesity in individuals at risk because
      of their genetic composition. Our understanding of the molecular pathways
      underlying common obesity is limited. During the last decade a handful of
      monogenic disorders leading to early, severe obesity in humans have been
      identified. All affect the central regulation of appetite. These conditions are
      rare, except for mutations in the melanocortin 4 receptor that account for about
      5% of morbidly obese patients (BMI > 40 kg/m). The identification of monogenic
      forms of obesity has contributed valuable insight into the regulation of appetite
      and development of obesity, although causal treatment only exists for leptin
      deficiency. In addition, several well defined Mendelian syndromes are associated
      with overweight and obesity. The molecular genetic cause is known for some of
      these syndromes, but how appetite and energy balance are affected is still
      unclear.

PMID- 16299562
TI  - [Magnetic resonance imaging of the small bowel].
AB  - BACKGROUND: Conventional small bowel enteroclysis is considered the principal
      radiological method to investigate the small bowel. However, the method has
      important limitations and magnetic resonance imaging (MRI) has been introduced as
      an alternative. MATERIAL AND METHODS: This review is based on the literature and
      our clinical experience. RESULTS AND INTERPRETATION: There are two main methods
      for MRI examination of the small bowel. One method uses a tube placed in the
      jejunum prior to the MRI examination and the other uses simple oral
      administration of contrast media. These methods are both shown to be as good as
      conventional X-ray examinations of the small bowel when used for follow up of
      patients with Crohn's disease. However, the resolution in MRI of the small bowel
      is insufficient to depict small superficial lesions. MRI should therefore be used
      as the preferred radiological method for follow up of patients with known Crohn's
      disease. When the primary diagnosis is not known, MRI should be used only as a
      supplement to more extensive investigations.

PMID- 16299563
TI  - [Brominated flame retardants may cause brain injuries in the fetus and the
      newborn].
AB  - BACKGROUND: Brominated flame retardants are incorporated into an ever-increasing
      number of ordinary consumer goods, which has lead to pollution of the
      environment, wildlife, food of animal origin, and human blood, adipose tissue,
      and mother's milk. This group of chemicals has a striking structural similarity
      with the thyroid hormones and may constitute a potential health risk by
      interfering with thyroid hormone homeostasis. MATERIAL AND METHODS: We focus on
      these features and discuss possible clinical consequences, on the basis of
      Medline searches and our own experience. RESULTS: The thyroid hormones are
      essential for normal brain development. Disruption of the hormonal balance may
      lead to serious and permanent defects of neurological functioning. Brominated
      flame retardants may interfere with thyroid synthesis, transport, receptor
      binding, and elimination. The clinical consequences have so far not been firmly
      established, but results from animal studies suggest that even subtle
      disturbances of thyroid homeostasis during pregnancy may have serious
      implications for the developing brain. INTERPRETATION: Numerous scientific
      reports confirm the neurotoxic potential of these chemicals. The foetus and
      newborn are especially vulnerable.

PMID- 16299564
TI  - [Congenital hypothyroidism and the impact of thyroxine treatment].
AB  - BACKGROUND: We have studied the significance of the thyroxine treatment for
      neuropsychological functioning in young adults with congenital hypothyroidism.
      SUBJECTS AND METHODS: This is a neuropsychological follow-up study of a three
      year cohort of early treated congenital hypothyroidism in Norway (N = 49) at age
      20. Siblings comprise the control group (N = 41, 21 years). RESULTS: The patient
      group performed weaker than the control group on cognitive and motor measures.
      They reported somewhat more psychosocial problems; fewer completed high school. A
      more severe hypothyroidism at the time of diagnosis was associated with a larger
      motor deficit at age 20. Better cognitive function in young adulthood was
      associated with a higher thyroxine starting dose and serum thyroxine level in the
      first years of life. Blood samples in young adulthood showed elevated thyrotropin
      levels in 45% of the patients. INTERPRETATION: This study supports the new
      guidelines for treatment of congenital hypothyroidism with a higher starting dose
      of 10-15 microg thyroxine/kg/24 hours. The young adults are in need of better
      medical follow up.

PMID- 16299565
TI  - [Growth and dietary intake among children with previous cow's milk allergy].
AB  - BACKGROUND: Approximately 2-3% of children develop allergy or intolerance to
      cow's milk and many of them go on a milk-free diet for a long time. Few studies
      have been done on growth and dietary intake among these children. MATERIAL AND
      METHODS: 28 children aged 6-10 who had recovered from cow's milk allergy, divided
      into groups "low-milk" and "ad lib milk", were compared with a control group of
      32 children of same age. Growth rates from age one and dietary intake at present
      age based on four days weighed dietary assessment were used. RESULTS: Among the
      allergic children at ages 6-10, 50% had developed tolerance to cow's milk
      protein, while 35% used some dairy products. A totally milk-free diet was kept by
      15%; these children were excluded from the study. The children with allergy had
      low body weight and height at ages one, two and four and at the present age
      compared with the controls. The energy intake was the same in both groups. The
      total sample had higher intake of sugar and lower intake of vitamin D than the
      recommended values. The 35% of children with restricted intake of cow's milk had
      lower intake of calcium, riboflavin and protein. The 50% of children with ad lib
      intake of milk products had a diet that differed little from that of the non
      allergic children. INTERPRETATION: There is a need for further studies on growth,
      dietary intake and development of tolerance that could give health workers better
      knowledge for dealing with this group of children.

PMID- 16299566
TI  - [Treatment of acne].

PMID- 16299567
TI  - [Nucleic-acid based diagnostics in clinical microbiology].
AB  - BACKGROUND: Detection of nucleic acids from infectious agents now has a
      fundamental role in diagnostic microbiology laboratories. Nucleic acid
      amplification methods have promoted this development. MATERIAL AND METHODS: In
      this study we give a review of the field based on searches in Medline and our own
      experience. RESULTS AND INTERPRETATION: Nucleic acid sequencing, hybridisation
      and electrophoresis complement the gene technology available for microbiological
      diagnosis. Recently, equipment for automated extraction of nucleic acids and real
      time quantitative PCR has contributed to faster, more reliable and robust nucleic
      acid detection. An increasing number of microbiological agents and virulence
      genes can now be diagnosed in a variety of patient samples and supplemented with
      additional nucleic acid-based methods for genotyping and quantitative monitoring
      of drug resistance and therapeutic response.

PMID- 16299570
TI  - [Emergency in-hospital anaesthesia assistance].
AB  - BACKGROUND: Anesthesiologists and nurse anaesthesists have important roles in the
      management of in-hospital medical emergencies, and in trauma management. We
      investigated the extent of these services provided by the department of
      anaesthesiology at St. Olav University Hospital in Trondheim in the year 2002.
      MATERIAL AND METHODS: Missions involving emergency medical assistance were
      identified by a computer search in the department's database. We assessed medical
      aspects, place, time, and type of intervention. RESULTS: We identified a total of
      646 missions, of which 501 occurred in the emergency department and 145 on the
      general wards. The majority (64%) occurred during on-call hours (4 pm-8 am). We
      found that as many as 4 to 7 missions occurred on any single day 40 times (i.e.
      days) during the year; which fits in with a Poisson statistical model. Trauma (50
      %) and cardiac arrest (20%) dominated the material. Other medical emergencies
      included seizures, cerebrovascular events, intoxication, respiratory arrest,
      cardiac arrhythmias, internal bleeding, pulmonary oedema and loss of
      consciousness. Airway management was important, as 61 patients received bag-valve
      mask ventilation and 164 were intubated and ventilated. INTERPRETATION: Staffing
      of anaesthesiology departments must take into account the possibility of sudden
      medical emergencies.

PMID- 16299569
TI  - [Molecular diagnostic techniques in gynaecologic cancer].
AB  - BACKGROUND: Our understanding of the genetic basis of gynaecologic cancer has
      increased. Still this is a major cause of death. Based on a review of the
      literature, we present molecular diagnostic tools no available for the prevention
      and characterisation of cancers in the ovaries, uterus and cervix. MATERIALS AND
      METHODS: The presentation is based on a limited literature search in PubMed,
      Medline, Cochrane, internet addresses for treatment protocols, and our own
      experiences. RESULTS: The cause of endometrial and ovarian cancer is mainly
      unknown. Around 5% of the cases are caused by inherited mutations in the BRCA1,
      BRCA2 or DNA repair genes. Special follow up is recommended for carriers of these
      mutations. Human papillomavirus (HPV) is the main cause of cervical cancer.
      Determination of the HPV type can contribute to a diagnosis, but it is not part
      of the screening programme. A more precise molecular diagnosis in endometrial and
      ovarian cancer can lead to development of new targeted therapy and tests for
      prediction of treatment response. Preliminary studies have given promising
      results, including studies of papillomavirus vaccines. INTERPRETATION: Detection
      of susceptibility genes, oncogenic viruses and prognostic markers are now useful
      tools in the prevention, diagnosis and treatment of gynaecologic cancer. Studies
      of the molecular tumour profile have shown promise for the development of new
      treatment strategies.

PMID- 16299571
TI  - [What are the clinical ethics committees doing?].
AB  - BACKGROUND: Clinical ethics committees have recently been established in nearly
      all Norwegian hospital trusts. To assess the quality and function of the
      committees, a national research project was initiated in 2004. METHODS: A
      questionnaire on composition, resources, qualifications, tasks and routines was
      mailed to all committees. The response rate was 75% (21 out of 28). RESULTS: The
      committees are interdisciplinary and meet on average nine times per year. Only
      three (14%) chairs have been given dedicated time. Ten (48%) committees have
      separate budgets. Major tasks include getting the committee established,
      educating employees, deliberations (cases and more general questions), and
      guidelines. Main issues are withholding and withdrawing treatment, communication,
      patient autonomy, involuntary treatment, and priority setting. 16 committees have
      specific deliberation procedures. Minutes were taken in approximately half of the
      case deliberations. Systematic evaluation is scarce. INTERPRETATION: During a
      short period the committees have increased their competence and served over 2000
      hospital employees, mainly through seminars. The committees probably already
      contribute to quality assurance in ethical decision making. The committees want
      more case consultations. Important challenges are obtaining sufficient resources,
      making the committees better known, and establishing routines.

PMID- 16299568
TI  - [Antineoplastic agents targeting tyrosine kinases].
AB  - BACKGROUND: Drugs that target tyrosine kinases belong to a new class of
      antineoplastic therapeutics, directed at cellular signalling mechanisms. Notes on
      the use of these agents and some of the clinical data are discussed in this
      review. METHODS: The article is based on a review of recent literature and the
      authors' personal experience. RESULTS AND INTERPRETATION: Receptor tyrosine
      kinases and intracellular tyrosine kinases regulate cellular events that may be
      involved in tumour development, such as proliferation, survival, and
      angiogenesis. Some of these agents are established in clinical practice, in
      particular the small-molecular tyrosine kinase inhibitor imatinib in the
      treatment of chronic myeloid leukaemia and gastrointestinal stromal tumours and
      the antibody trastuzumab in the treatment of breast cancer. Inhibitors of
      epidermal growth factor receptor (EGFR) and other tyrosine kinases are either
      established in clinical practice or under clinical investigation.

PMID- 16299573
TI  - [Measurement of patient-centered communication].

PMID- 16299576
TI  - [New global strategy for maternal and child health].

PMID- 16299574
TI  - [Hereditary breast cancer].
AB  - Norwegian health care for women at risk of inherited breast cancer conforms with
      the European consensus guidelines published in 1999 and the Norwegian legislation
      regulating the use of predictive genetic testing. This paper represents a
      consensus between all medical genetic institutions in Norway handling inherited
      breast cancer through the Norwegian Group on Inherited Cancer. It is an update
      based on new knowledge, the structure of our health service and locally available
      technology and health care resources. The indications for referring patients to
      genetic testing are maintained. The demonstration of local founder BRCA1
      mutations has been used to develop a high capacity for testing for these
      mutations. Mutation carriers should be offered annual MRI of the breasts for
      early diagnosis. Oophorectomy at end of childbearing ages is advocated in BRCA
      mutation carriers and breast-ovarian kindreds. The clinical geneticists have the
      role of coordinating health service to those in need, and are required to
      collaborate to present the empirical results of the effects of the interventions.

PMID- 16299572
TI  - [Consultations with specialists in private practice in a Norwegian district].
AB  - BACKGROUND: After the Norwegian hospital reform of 2002, there has been increased
      acceptance of private-sector health-care providers. Still, the use of specialist
      services in private practice is less well documented. This article explores the
      use of private specialist health care in the south-east of Norway. MATERIAL AND
      METHODS: The article is based on several sources of data, including data from the
      Norwegian Patient Register and from the National Insurance Administration on
      reimbursements. Also a survey was sent out to a sample of general practitioner;
      in-depth interviews were carried out with a sample of hospital physicians and
      private specialists. RESULTS: The article shows that private specialists with
      contract with Helse Ost provided 151 consultations per 1000 inhabitants over the
      period September to November 2003, while the public outpatient clinics provided
      186 consultations. The service provision varies geographically and between
      specialties. In one county the use of private specialists is 174 consultations
      per 1000 inhabitants; in another it is 80 per 1000 inhabitants. Private-sector
      specialists within the fields of eye, ear-nose-throat and skin provided two
      thirds of all outpatient services in their respective fields. INTERPRETATION: The
      results indicate that the services of specialists in private practice should be
      more focused on and discussed in relation to integrated healthcare and the
      relationship between specialised hospital services and primary healthcare.

PMID- 16299578
TI  - [Prostaglandin synthesis, redox regulation and pain].

PMID- 16299581
TI  - [Treatment of stuttering with the help of technical aids].

PMID- 16299582
TI  - [The state is losing money on the generic drug exchange].

PMID- 16299583
TI  - [Conjunctivitis in children].

PMID- 16299584
TI  - Use of three-dimensional collagen gels to study mechanotransduction in T47D
      breast epithelial cells.
AB  - Several pathological and disease conditions can alter the mechanical properties
      of the extracellular matrix (ECM). Conversely, some diseases may arise from
      changes in the density or rigidity of the ECM. This necessitates the use and
      development of in vitro models to understand how both biophysical and biochemical
      signals regulate complex cellular behaviors. T47D breast epithelial cells will
      differentiate into duct-like tubules when cultured in a floating three
      dimensional (3D) collagen gel, but not a 3D collagen gel that is left attached to
      the culture dish. This paper details several protocols we have developed for
      analyzing breast cell biology in 3D matrices, including culturing cells in 3D
      collagen gels, immunostaining cellular structures, and performing biochemical
      procedures directly from cells embedded in collagen gels.

PMID- 16299585
TI  - Maternal expression relaxes constraint on innovation of the anterior determinant,
      bicoid.
AB  - The origin of evolutionary novelty is believed to involve both positive selection
      and relaxed developmental constraint. In flies, the redesign of anterior
      patterning during embryogenesis is a major developmental innovation and the
      rapidly evolving Hox gene, bicoid (bcd), plays a critical role. We report
      evidence for relaxation of selective constraint acting on bicoid as a result of
      its maternal pattern of gene expression. Evolutionary theory predicts 2-fold
      greater sequence diversity for maternal effect genes than for zygotically
      expressed genes, because natural selection is only half as effective acting on
      autosomal genes expressed in one sex as it is on genes expressed in both sexes.
      We sample an individual from ten populations of Drosophila melanogaster and nine
      populations of D. simulans for polymorphism in the tandem gene duplicates bcd,
      which is maternally expressed, and zerknullt (zen), which is zygotically
      expressed. In both species, we find the ratio of bcd to zen nucleotide diversity
      to be two or more in the coding regions but one in the noncoding regions,
      providing the first quantitative support for the theoretical prediction of
      relaxed selective constraint on maternal-effect genes resulting from sex-limited
      expression. Our results suggest that the accelerated rate of evolution observed
      for bcd is owing, at least partly, to variation generated by relaxed selective
      constraint.

PMID- 16299586
TI  - Evidence of a large novel gene pool associated with prokaryotic genomic islands.
AB  - Microbial genes that are "novel" (no detectable homologs in other species) have
      become of increasing interest as environmental sampling suggests that there are
      many more such novel genes in yet-to-be-cultured microorganisms. By analyzing
      known microbial genomic islands and prophages, we developed criteria for
      systematic identification of putative genomic islands (clusters of genes of
      probable horizontal origin in a prokaryotic genome) in 63 prokaryotic genomes,
      and then characterized the distribution of novel genes and other features. All
      but a few of the genomes examined contained significantly higher proportions of
      novel genes in their predicted genomic islands compared with the rest of their
      genome (Paired t test = 4.43E-14 to 1.27E-18, depending on method). Moreover, the
      reverse observation (i.e., higher proportions of novel genes outside of islands)
      never reached statistical significance in any organism examined. We show that
      this higher proportion of novel genes in predicted genomic islands is not due to
      less accurate gene prediction in genomic island regions, but likely reflects a
      genuine increase in novel genes in these regions for both bacteria and archaea.
      This represents the first comprehensive analysis of novel genes in prokaryotic
      genomic islands and provides clues regarding the origin of novel genes. Our
      collective results imply that there are different gene pools associated with
      recently horizontally transmitted genomic regions versus regions that are
      primarily vertically inherited. Moreover, there are more novel genes within the
      gene pool associated with genomic islands. Since genomic islands are frequently
      associated with a particular microbial adaptation, such as antibiotic resistance,
      pathogen virulence, or metal resistance, this suggests that microbes may have
      access to a larger "arsenal" of novel genes for adaptation than previously
      thought.

PMID- 16299587
TI  - Drosophila tan encodes a novel hydrolase required in pigmentation and vision.
AB  - Many proteins are used repeatedly in development, but usually the function of the
      protein is similar in the different contexts. Here we report that the classical
      Drosophila melanogaster locus tan encodes a novel enzyme required for two very
      different cellular functions: hydrolysis of N-beta-alanyl dopamine (NBAD) to
      dopamine during cuticular melanization, and hydrolysis of carcinine to histamine
      in the metabolism of photoreceptor neurotransmitter. We characterized two tan
      like P-element insertions that failed to complement classical tan mutations. Both
      are inserted in the 5' untranslated region of the previously uncharacterized gene
      CG12120, a putative homolog of fungal isopenicillin-N N-acyltransferase (EC
      2.3.1.164). Both P insertions showed abnormally low transcription of the CG12120
      mRNA. Ectopic CG12120 expression rescued tan mutant pigmentation phenotypes and
      caused the production of striking black melanin patterns. Electroretinogram and
      head histamine assays indicated that CG12120 is required for hydrolysis of
      carcinine to histamine, which is required for histaminergic neurotransmission.
      Recombinant CG12120 protein efficiently hydrolyzed both NBAD to dopamine and
      carcinine to histamine. We conclude that D. melanogaster CG12120 corresponds to
      tan. This is, to our knowledge, the first molecular genetic characterization of
      NBAD hydrolase and carcinine hydrolase activity in any organism and is central to
      the understanding of pigmentation and photoreceptor function.

PMID- 16299588
TI  - All paired up with no place to go: pairing, synapsis, and DSB formation in a
      balancer heterozygote.
AB  - The multiply inverted X chromosome balancer FM7 strongly suppresses, or
      eliminates, the occurrence of crossing over when heterozygous with a normal
      sequence homolog. We have utilized the LacI-GFP: lacO system to visualize the
      effects of FM7 on meiotic pairing, synapsis, and double-strand break formation in
      Drosophila oocytes. Surprisingly, the analysis of meiotic pairing and synapsis
      for three lacO reporter couplets in FM7/X heterozygotes revealed they are paired
      and synapsed during zygotene/pachytene in 70%-80% of oocytes. Moreover, the
      regions defined by these lacO couplets undergo double-strand break formation at
      normal frequency. Thus, even complex aberration heterozygotes usually allow high
      frequencies of meiotic pairing, synapsis, and double-strand break formation in
      Drosophila oocytes. However, the frequencies of failed pairing and synapsis were
      still 1.5- to 2-fold higher than were observed for corresponding regions in
      oocytes with two normal sequence X chromosomes, and this effect was greatest near
      a breakpoint. We propose that heterozygosity for breakpoints creates a local
      alteration in synaptonemal complex structure that is propagated across long
      regions of the bivalent in a fashion analogous to chiasma interference, which
      also acts to suppress crossing over.

PMID- 16299589
TI  - The association of tetrameric acetylcholinesterase with ColQ tail: a block normal
      mode analysis.
AB  - Acetylcholinesterase (AChE) rapidly hydrolyzes acetylcholine in the neuromuscular
      junctions and other cholinergic synapses to terminate the neuronal signal. In
      physiological conditions, AChE exists as tetramers associated with the proline
      rich attachment domain (PRAD) of either collagen-like Q subunit (ColQ) or proline
      rich membrane-anchoring protein. Crystallographic studies have revealed that
      different tetramer forms may be present, and it is not clear whether one or both
      are relevant under physiological conditions. Recently, the crystal structure of
      the tryptophan amphiphilic tetramerization (WAT) domain of AChE associated with
      PRAD ([WAT]4PRAD), which mimics the interface between ColQ and AChE tetramer,
      became available. In this study we built a complete tetrameric mouse [AChE(T)]4
      ColQ atomic structure model, based on the crystal structure of the [WAT]4PRAD
      complex. The structure was optimized using energy minimization. Block normal mode
      analysis was done to investigate the low-frequency motions of the complex and to
      correlate the structure model with the two known crystal structures of AChE
      tetramer. Significant low-frequency motions among the catalytic domains of the
      four AChE subunits were observed, while the [WAT]4PRAD part held the complex
      together. Normal mode involvement analysis revealed that the two lowest frequency
      modes were primarily involved in the conformational changes leading to the two
      crystal structures. The first 30 normal modes can account for more than 75% of
      the conformational changes in both cases. The evidence further supports the idea
      of a flexible tetramer model for AChE. This model can be used to study the
      implications of the association of AChE with ColQ.

PMID- 16299591
TI  - If you've got it, flaunt it: ingested alkaloids affect corematal display behavior
      in the salt marsh moth, Estigmene acrea.
AB  - Plant-derived pyrrolizidine alkaloids play an important role in the biology of
      the salt marsh moth, Estigmene acrea (Lepidoptera: Arctiidae). They are
      phagostimulants for larvae and they stimulate the growth and development of adult
      male androconial organs called coremata. In this study, we have shown that the
      pyrrolizidine alkaloid monocrotaline N-oxide (MNO) fed to larvae also affects the
      courtship behavior of adult males. Males fed a diet containing MNO display their
      coremata while males fed on the same diet without alkaloid rarely display. This
      explains why it has been difficult to replicate field observations of the
      "lekking" behavior of this species in the laboratory where animals are frequently
      raised on commercially available diets devoid of alkaloids. Corematal inflation
      was observed in isolated males and in laboratory leks. The effect of larvae
      feeding on pyrrolizidine alkaloid on the reproductive behavior of adults suggests
      that this substance may modify the development of the moth's nervous system and
      contribute to their unusual dual mating strategies. MNO was also shown to be an
      adequate precursor for the production of the courtship pheromone hydroxydanaidal.

PMID- 16299590
TI  - Stealth proteins: in silico identification of a novel protein family rendering
      bacterial pathogens invisible to host immune defense.
AB  - There are a variety of bacterial defense strategies to survive in a hostile
      environment. Generation of extracellular polysaccharides has proved to be a
      simple but effective strategy against the host's innate immune system. A
      comparative genomics approach led us to identify a new protein family termed
      Stealth, most likely involved in the synthesis of extracellular polysaccharides.
      This protein family is characterized by a series of domains conserved across
      phylogeny from bacteria to eukaryotes. In bacteria, Stealth (previously
      characterized as SacB, XcbA, or WefC) is encoded by subsets of strains mainly
      colonizing multicellular organisms, with evidence for a protective effect against
      the host innate immune defense. More specifically, integrating all the available
      information about Stealth proteins in bacteria, we propose that Stealth is a D
      hexose-1-phosphoryl transferase involved in the synthesis of polysaccharides. In
      the animal kingdom, Stealth is strongly conserved across evolution from social
      amoebas to simple and complex multicellular organisms, such as Dictyostelium
      discoideum, hydra, and human. Based on the occurrence of Stealth in most
      Eukaryotes and a subset of Prokaryotes together with its potential role in
      extracellular polysaccharide synthesis, we propose that metazoan Stealth
      functions to regulate the innate immune system. Moreover, there is good reason to
      speculate that the acquisition and spread of Stealth could be responsible for
      future epidemic outbreaks of infectious diseases caused by a large variety of
      eubacterial pathogens. Our in silico identification of a homologous protein in
      the human host will help to elucidate the causes of Stealth-dependent virulence.
      At a more basic level, the characterization of the molecular and cellular
      function of Stealth proteins may shed light on fundamental mechanisms of innate
      immune defense against microbial invasion.

PMID- 16299592
TI  - Genetic differentiation among geographic populations of Gonatocerus ashmeadi, the
      predominant egg parasitoid of the glassy-winged sharpshooter, Homalodisca
      coagulata.
AB  - The aim of genetically comparing different populations of the same species of
      natural enemies is to identify the strain that is most adapted to the environment
      where it will be released. In the present study, Inter-Simple Sequence Repeat
      Polymerase Chain Reaction (ISSR-PCR) was utilized to estimate the population
      genetic structure of Gonatocerus ashmeadi (Girault) (Hymenoptera: Mymaridae), the
      predominant egg parasitoid of Homalodisca coagulata (Say)
      (Homoptera:Cicadellidae), the glassy-winged sharpshooter. Six populations from
      throughout the U.S. and a population from Argentina identified as near G.
      ashmeadi were analyzed. Four populations (California; San Antonio, Texas;
      Weslaco, Texas [WTX-2]; and Florida) were field collected and two (Louisiana and
      Weslaco, Texas [WTX-1]) were reared. Three ISSR-PCR reactions were pooled to
      generate 41 polymorphic markers among the six U.S. populations. Nei's expected
      heterozygosity values (h), including the reared population from Louisiana, were
      high (9.01-14.3%) for all populations, except for a reared population from WTX-1
      (2.9%). The total genetic diversity value (Ht) for the field populations was high
      (23%). Interestingly, the Florida population that was collected from one egg mass
      (siblings) generated the greatest number of polymorphic markers (20) and was
      observed with the highest gene diversity value (14.3%). All populations, except
      WTX-2 generated population-specific markers. Comparison of genetic
      differentiation estimates, which evaluate the degree of genetic subdivision,
      demonstrated good agreement between G(ST) and theta values, 0.38 and 0.50,
      respectively for field populations, and 0.44 and 0.50, respectively for all
      populations. Genetic divergence (D) indicated that the WTX-1 population was the
      most differentiated. Average D results from the Argentina population support the
      taxonomic data that it is a different species. The present results estimate the
      population genetic structure of G. ashmeadi, demonstrating genetic divergence and
      restricted gene flow (Nm = 0.83) among populations. These results are of interest
      to the Pierce's disease/glassy-winged sharpshooter biological control program
      because the key to successful biological control may not be in another species,
      but instead in different geographic races or biotypes.

PMID- 16299593
TI  - Extracting single genomes from heterogenous DNA samples: a test case with
      Carsonella ruddii, the bacterial symbiont of psyllids (Insecta).
AB  - Analysis of many bacterial genomes is impeded by the inability to separate
      individual species from complex mixtures of cells or to propagate cells in pure
      culture. This problem is an obstacle to the study of many bacterial symbionts
      that live intracellularly in insects and other animals. To recover bacterial DNA
      from complex samples, we devised a method that facilitates the cloning of DNA
      fragments of distinctive G+C contents in order to generate shotgun DNA libraries
      enriched in inserts having a specific base composition. DNA preparations are
      first treated with a restriction enzyme having a common cleavage site in a
      particular genome and then shotgun cloned following size-fractionation. This
      method was applied to whole bacteriomes of the psyllid, Pachypsylla venusta,
      which harbors the bacterial symbiont Candidatus Carsonella ruddii. The resulting
      libraries were highly enriched in bacterial sequences. Through the use of
      alternate enzymes and partial digests, this technique can be adapted to yield
      virtually pure DNA libraries for individual bacterial species.

PMID- 16299594
TI  - The effect of development time on the fitness of female Trichogramma evanescens.
AB  - Trichogramma are facultative gregarious egg parasitoids that attack a wide range
      of lepidopterous eggs. Because hosts in which parasitoids develop vary in terms
      of available food, the progeny produced by parasitoid females vary in size and
      fitness. While one might expect that the developmental rate and emergence rhythm
      should be similar for all individuals reared under the same environmental
      conditions, variations in the duration of development of individuals reared under
      uniform conditions have been found in several insect species. In the Hymenopteran
      egg parasitoid Trichogramma evanescens Westwood (Hymenoptera: Trichogrammatidae)
      adults emerge at the beginning of the photoperiod on two consecutive days. Longer
      development may influence the fitness of adults and have an impact on mating
      opportunities. Size, longevity and daily and lifetime fecundity were measured for
      female T. evanescens that developed in nine and ten days. We observed a
      significant relationship between size and both longevity and lifetime fecundity.
      While early emerging females did not live longer and did not produce progeny with
      a different sex-ratio than females that emerged later, they were larger and
      produced more progeny than late females. We conclude that early emerging females
      have a higher fitness than late emerging females T. evanescens.

PMID- 16299595
TI  - Functional responses of coccinellid predators: an illustration of a logistic
      approach.
AB  - The functional response parameters and patterns of three coccinellid predators,
      Cheilomenes sexmaculata, Propylea dissecta, and Coccinella transversalis
      (Coleoptera: Coccinellidae) were evaluated to find out how these predators
      respond at two different prey species across various prey densities levels. All
      three predators exhibited a decelerating curve Type II response determined by a
      logistic regression model. The linear reciprocal transformation of Holling's disc
      equation was used to further evaluate the parametric values. C. sexmaculata
      responded maximally, followed by C. transversalis and P. dissecta, in terms of
      consumption of the aphids, Aphis craccivora and Myzus persicae, with suitable
      values of coefficient of attack rates and handling times on these prey species.
      Differences in handling times were found to be significant within and between the
      predatory species on both prey species indicating that predators respond
      differentially to prey species. Differences in coefficients of attack rates,
      however, did not vary significantly in most of the treatments. The potential role
      of these predators in biocontrol of A. craccivora and M. persicae suggests that
      C. sexmaculata is the best predator for the management of both prey species,
      particularly A. craccivora. However, further field based studies are needed to
      confirm this hypothesis.

PMID- 16299596
TI  - Infection with the insect virus Hz-2v alters mating behavior and pheromone
      production in female Helicoverpa zea moths.
AB  - The effect of Hz-2V virus infection on the reproductive physiology and behavior
      of infected Helicoverpa zea female moths was examined. In the absence of males,
      infected females exhibited calling behavior and called as often but for shorter
      periods on average than control females. As expected, control females mated with
      males for extend periods when they were present and did not call after mating,
      while virus-infected females made many frequent contacts with males and continued
      to call even after these contacts. Virus-infected females were found to produce
      five to seven times more pheromone than control females and attracted twice as
      many males as did control females in flight tunnel experiments. The ability of Hz
      2V to alter the physiology and behavior of infected females observed here may
      serve to facilitate the transmission of virus in insect populations.

PMID- 16299597
TI  - Conditional immune-gene suppression of honeybees parasitized by Varroa mites.
AB  - The ectoparasitic mite, Varroa destructor, is the most destructive parasite of
      managed honeybee colonies worldwide. Since V. destructor transfers pathogens to
      honeybees, it may be adaptive for bees to respond to mite infestation by
      upregulating their immune responses. Mites, however, may overcome the host's
      immune responses by suppressing them, which could facilitate the mite's ability
      to feed on hemolymph. A humoral immune response of bees parasitized by V.
      destructor may be detected by studying the expression levels of antibacterial
      peptides, such as abaecin and defensin, known to be immune-responsive. Expression
      levels for these two antibacterial peptides changed non-linearly with respect to
      the number of mites parasitizing honeybee pupae. Bees exposed to low or moderate
      number of mites had fewer immune-related transcripts than pupae that were never
      parasitized or pupae with high mite loads. Although many of the pupae tested
      indicated the presence of bacteria, no correlation with mite numbers or immune
      response levels existed. All bees tested negative for acute paralysis and Kashmir
      bee viruses known to be vectored by V. destructor.

PMID- 16299599
TI  - The nest architecture of the ant, Camponotus socius.
AB  - The architecture of subterranean nests of the ant Camponotus socius was studied
      from casts of plaster or metal. Twenty-four such casts are illustrated using
      stereo pairs of images. After study, plaster casts were dissolved to retrieve the
      workers embedded in them, providing a census of the ants that excavated the nest.
      Nests were up to 60 cm deep, and were composed of descending shafts connecting up
      to about 10 horizontal chambers. Nest volume ranged up to almost 800 cm and total
      chamber area up to almost 500 cm. Both volume and area were closely and
      positively related to the number of workers in the nest. Nest enlargement
      occurred through the simultaneous enlargement of chambers, deepening of the nest
      and addition of more chambers. Chamber enlargement contributed most to nest
      growth. Chambers near the surface were elongate and tunnel-like, while deeper
      chambers were more compact in outline. As chambers were enlarged, their outlines
      became more complex and lobed. Workers were polymorphic with clearly
      distinguishable minor and major workers. The headwidth of minors averaged 1.45 to
      1.65 mm, and that of majors 2.30 to 2.80 mm. The mean headwidth of minors
      increased significantly as the proportion of major workers increased, but the
      trend of major headwidths fell short of significance. The numerical proportion of
      majors ranged from 3% to 38% and averaged 15% of the workers, while their biomass
      proportion ranged from 10% to 75%, averaging about 50%. The queen was recovered
      in 6 of the 14 plaster nests, suggesting that the average colony of this
      polydomous species has 2.3 nests. Because of the lateness of the season when
      casts were made (October), only two nests contained significant amounts of brood.
      The possible functional roles of nest architecture in ants are discussed.

PMID- 16299598
TI  - Expression, purification and characterization of methyl DNA binding protein from
      Bombyx mori.
AB  - A cDNA clone encoding methyl DNA binding domain-containing protein (bMBD2/3) was
      obtained by homology searches using a Bombyx mori fat body cDNA library. The cDNA
      encoded a polypeptide with 249 amino acids sharing 54% similarity with the methyl
      DNA binding protein from Drosophila melanogaster. To characterize the biochemical
      properties of bMBD2/3, the clone was expressed in Escherichia coli as His-tagged
      protein. The recombinant protein was purified to homogeneity using Ni-NTA
      superflow resin and heparin agarose. The protein showed specific methyl DNA
      binding activity and was phosphorylated by protein kinase in vitro.
      Immunoblotting using the purified antibody indicated that bMBD2/3 was expressed
      in almost all tissues. Using west-western blotting analysis, some proteins that
      interact with bMBD2/3 were identified in the brain. This is the first report that
      insect MBD is phosphorylated and is present in adult tissues. These results
      suggest that bMBD2/3 plays important roles in the DNA methylation-specific
      transcription of Bombyx mori.

PMID- 16299600
TI  - Sexual selection and mating advantages in the giant sperm species, Drosophila
      bifurca.
AB  - Mate choice may be exercised by either sex; however, females are generally
      choosier than males because they invest more in their gametes. Female choice is
      often based on direct benefits, such as better reproductive output, whereas male
      choice appears to be based on differences in female fecundity. However, when
      gamete production is limited, sexual selection theories predict that mate choice
      will be decisive for reproductive success in both sexes. Here, we investigate how
      mating advantage is achieved in Drosophila bifurca, a giant sperm species in
      which both sexes produce only a few gametes. Our initial expectations were as
      follows: (1) females would discriminate against sperm-depleted males to avoid
      fertility cost; and (2) males would discriminate against inseminated females to
      reduce sperm competition and increase the assurance of paternity of individual
      gametes. Differences in courtship behaviors were analyzed with regard to the
      sexual maturity, which is reached after 22 days in males at 21 degrees C, and the
      reproductive history of both sexes (inseminated versus virgin for females, and
      sperm-depleted versus sperm-loaded for males). Our results show that: (1) sexual
      immaturity precludes mating in both sexes; (2) virgin females do not discriminate
      between sperm-loaded and sperm-depleted males, and (3) males mate preferentially
      with virgin females, because inseminated females fend off the male, which tended
      to bring male courtship to an end. Female remating was limited, but increased
      significantly when the first male was sperm-depleted. Contrary to our initial
      expectations, these findings suggest that male sperm depletion does not affect
      female mating preference, whereas the success of male courtship is driven by
      female behavior. The possibility that female remating was only promoted in
      response to low sperm transfer is discussed in relation to the gametic system of
      this species.

PMID- 16299601
TI  - Dispersal patterns and clumping behaviors in the beetle Trichoton sordidum.
AB  - Although a significant number of behavioral studies of desert tenebrionids have
      been done, almost nothing is recorded of Trichoton sordidum (LeConte)
      (Coleoptera: Tenebrionidae), an inhabitant of the sunny, sparsely vegetated
      US/Mexican borderlands. For this small, flightless beetle successful predator
      evasion and adaptation to a desert environment has required development of
      complicated, quickly utilizable behavioral mechanisms for regulating exposure to
      extremes of heat, light, humidity, and habitat structure. In this study, T.
      sordidum was exposed to sudden changes in temperature, illumination, and habitat
      complexity, and some patterns representing its normal aggregation were recorded.
      Minimum Risk Distribution models (Floater 2001) predict changes in spatial
      distribution patterns of groups of individuals as they are exposed to
      environmental change. A successful species must have a large percentage of
      individuals adhering to changes with a set pattern of behaviors. All groups of T.
      sordidum tested demonstrated both rapid and cohesive dispersal patterns. They
      normally showed little tendency toward clustering, except clear adhesive
      aggregation patterns in cases of limited resources in a fragmented environment.
      Under conditions of extreme heat or light, aggregations in the form of clumping
      did occur. The formation of clumps from simple two-stacks to groups of up to ten
      is documented here. The sophistication, consistency of use, and rapid initiation
      of clumps suggest clumping might well be a highly evolved and successful
      mechanism for group threat evasion. The morphology of T. sordidum shows how
      clumping is achieved. An examination of the conditions leading to clumping gives
      clues to why clumps are formed.

PMID- 16299602
TI  - Squamous cell carcinoma of the oral tissues: a comprehensive review for oral
      healthcare providers.
AB  - North Americans in 2004 were projected to die from oral and pharyngeal cancer at
      a rate of 1.2 per hour. Oral healthcare providers can be instrumental in reducing
      the incidence of oral and pharyngeal premalignant and malignant lesions by
      identifying patients with high-risk behavior, educating their patients about the
      consequences of their high-risk behavior, and by early detection of premalignant
      and malignant conditions. The fact only 34% of the cancers of the oral cavity and
      larynx are localized at the time of diagnosis and evidence that at least one
      third of the patients diagnosed with an oral or pharyngeal malignancy have
      undergone oral cancer screening within the past three years suggests the current
      protocol for the early detection of pre-malignant or malignant changes appears to
      be deficient. To facilitate early diagnosis, oral healthcare providers must take
      into consideration the capriciousness of oral cancer and must be familiar with
      the availability and application of diagnostic modalities beyond conventional
      visual inspection and palpation of oral soft tissues. This article provides a
      comprehensive review of the disease for healthcare professionals.

PMID- 16299603
TI  - Effect of placement techniques on the marginal adaptation of Class V composite
      restorations.
AB  - STATEMENT OF THE PROBLEM: Several techniques are proposed for the restoration of
      Class V cavities but there is no agreement in the literature as to which
      technique is more effective. PURPOSE: To evaluate the effect of different
      techniques of composite increment placement on the marginal adaptation of Class V
      restorations. METHODS AND MATERIALS: Twenty-four human molars were selected and
      prepared with standardized saucer-shaped cavity dimensions of 3.0 mm (occlusal
      gingival), 2.0 mm (mesial-distal), and 2.0 mm (depth). The margins are in
      reference to the cemento-enamel junction with 1.5 mm being located on enamel and
      1.5 mm on dentin. The cavities were randomly assigned into three groups (n=8) and
      restored with composites as follows: Group 1, the occlusal increment was placed
      and cured first followed by the gingival increment; Group 2, the gingival
      increment was placed and cured first followed by the occlusal increment; and
      Group 3, the cavities were restored with one bulk increment. Restorations were
      immediately finished and stored for 24 h in tap water. Specimens were subjected
      to thermocycling (1000 cycles, 5 degrees C to 55 degrees C, 30 s dwell time) and
      immersed in 0.5% basic fuchsin solution for 24 h in room temperature. After
      rinsing with running water, the restorations were sectioned longitudinally and
      enamel and dentin margins were evaluated and scored according to the microleakage
      on a 0-3 scale. Data were subjected to Kruskal-Wallis test at p<0.05. RESULTS:
      Median of microleakage scores for all evaluated groups was zero. No statistical
      difference was observed among the three groups both in enamel (p = 0.5929) and
      dentin (p = 0.3679) margins CONCLUSION: The placement technique did not influence
      the marginal adaptation of moderate Class V restorations. CLINICAL SIGNIFICANCE:
      No differences on marginal adaptation were observed when restoring conservative
      Class V cavities using incremental or bulk placement techniques.

PMID- 16299604
TI  - The significance of marginal gap and overextension measurement in the evaluation
      of the fit of complete crowns.
AB  - INTRODUCTION: An important criterion for the success of a crown is marginal fit.
      However, in the patient's mouth fit can only be evaluated by subjective methods.
      This study describes the correlation between objective marginal fit and its
      subjective evaluation by dentists and dental technicians. MATERIALS AND METHODS:
      Thirty human premolars and molars were randomly divided into six groups and
      prepared with a shoulder. For each of the six groups, complete crowns were made
      of different alloys and technologies (casting: AuAgCu, AuPdPt, PdAgAu, CoCrMo,
      and Ti; milling: Ti). The crowns were cemented with provisional cement. Ten
      dentists and 10 technicians were asked to evaluate the fit of the crowns with a
      new dental explorer. The crowns were then cleaned and cemented with a zinc-oxide
      phosphate-cement. The marginal gap and a possible overextended margin of the
      crowns were examined under a special 4x light microscope with a magnification
      level of 560 X. The means of the gaps and the overextended margins were
      calculated for each group. Significances were detected by analysis of variance
      (ANOVA) and the post-hoc-test (Bonferroni, p<0.05). Correlations between
      objective measuring and subjective evaluation were evaluated using the Pearson
      test. The influence of the measured values on the subjective evaluation was
      determined by regression analyses. RESULTS: Crowns made from different alloys and
      technologies showed partly significantly (p<0.05) different marginal gaps (mean
      ranging from 35 microm to 92 microm) and significantly (p<0.05) different
      overextended margins (mean ranging from 40 microm to 149 microm). There were
      significant correlations (p<0.05) between subjective findings and objective data.
      Significant correlations (p<0.01) were also found between the subjective findings
      of dentists and technicians. Compared to the marginal gap, only the overextended
      margin had a significant influence (p=0.00) on the subjective evaluations of the
      clinicians. CONCLUSION: Crowns from different alloys and technologies showed
      differences in marginal fit. Marginal gap and the overextension of the crowns
      significantly correlated with the subjective evaluation of their fit by dentists
      and dental technicians. For the decision of the clinicians, whether a crown is
      acceptable, overextension was more important than marginal gap.

PMID- 16299605
TI  - The color differences between different thicknesses of resin veneered over
      amalgam.
AB  - STATEMENT OF PROBLEM: Composites and compomers are popular in dental practice.
      However, little is known about their esthetic appearance as veneering restorative
      materials over amalgam restorations. PURPOSE: This in vitro study was designed to
      assess the color differences of composite and compomer restorative materials,
      placed in thicknesses of 1 mm and 2 mm over amalgam. MATERIAL AND METHODS: Thirty
      six cylindrical Teflon molds were filled with amalgam (13 mm diameter, 2 mm
      thickness) and stored at 37 degrees C and 100% relative humidity for 7 days. Nine
      veneers (for each thickness of 1 and 2 mm) were fabricated from four types of
      tooth-colored restorative material, Dyract AP (DYR), Compoglass F (COMP),
      Herculite XRV (XRV), and Vitalecense (VIT), over amalgam specimens using Teflon
      split molds and following the manufacturers' instructions. A spectrophotometer
      was used to measure the color difference DeltaE* between the two thicknesses.
      RESULTS: Color difference DeltaE* values for 1 mm thickness veneers [XRV (2.52),
      Comp (5.46), VIT (6.73), and DYR (6.88)] were statistically significantly higher
      than the 2 mm thickness [XRV (1.32), Comp (3.24), VIT (4.89), and DYR (4.83)].
      Although the XRV material had the lowest DeltaE* values, no statistically
      significant difference was found between the two thicknesses. The color
      measurements at L*, a*, and b* showed most materials became darker in color at
      either thickness. CONCLUSION: The thicker veneer specimens were found to be
      closer in color to the controls than the thinner specimens. Only XRV had color
      differences (DeltaE*) small enough to be considered clinically acceptable (2.52
      and 1.32 at 1 mm and 2 mm, respectively). CLINICAL IMPLICATIONS: In this in vitro
      study the color of XRV was affected the least when veneered on amalgam. Opaquers
      may be needed to be used with thinner veneers to minimize the effect of amalgam
      background.

PMID- 16299607
TI  - Load-to-fracture value of different all-ceramic crown systems.
AB  - OBJECTIVES: The purpose was to investigate the potential difference in the load
      to-fracture values of several all-ceramic crown systems. Five different coping
      reinforced all-ceramic crown systems were selected. Ten crowns from each system
      were fabricated and luted to standardized titanium dies. METHODS: The study
      consisted of five groups of ten samples each, all luted using G.C. Link Max resin
      adhesive cement. Group A: IPS Eris, Group B: Cerac In-lab Alumina coping, Group
      C: Cerac In-lab Zirconia coping, Group D: Procera AllCeram Alumina coping, and
      Group E: Procera Zirconia coping. Following cementation, the samples were placed
      under a 5 Kg static load for 10 minutes insuring proper seating and stored in
      100% humidity for one week. All samples were visually inspected prior to testing
      and were loaded to fracture at the rate of 0.5 mm/min using a universal-testing
      machine. RESULTS: Group A = 321.49 KgF +/- 113.69 (S.D.), Group B = 288.63 +/-
      102.82 (S.D.), Group C = 266.58 +/- 69.17 (S.D.), Group D = 295.49 +/- 80.54
      (S.D.), and Group E = 420.37 +/- 82.45 (S.D.). The data were analyzed using an
      unpaired t-test; this indicated a statistical difference between group E and all
      of the others (P-value =0.039). CONCLUSIONS: We concluded under these conditions,
      the Procera Zirconia crown system has significant higher load-to-fracture value
      than several other all-ceramic crown systems.

PMID- 16299608
TI  - Perceived sources of stress within a dental educational environment.
AB  - The aim of this study was to identify the perceived sources of stress among
      dental students, dental hygiene students, and dental technology students enrolled
      at Jordan University of Science and Technology (JUST). The modified dental
      environment stress questionnaire was administered to 183 students. The perceived
      stressors varied between major and year. Dental students gave high scores for
      examinations, reduced holidays, inadequate time for relaxation, fear of failure,
      completing clinical requirements, and differences in opinion between staff.
      Dental hygiene students gave the highest scores for uncertainty about the field
      of study as future career, examinations, inadequate clinical training and
      supervision, inadequate relaxation, and discrimination between students. Dental
      technology students also gave high scores for uncertainty about future career,
      examinations, approachability of the staff, inadequate relaxation, and completing
      requirements. Females are more stressed than males with regard to personal
      factors. Dental technology and/or dental hygiene students have significantly
      higher scores than dental students in 12 items. Students who reported their first
      choice of study was not their current field of study showed more stress
      concerning their future careers. The high scores reported for some stressors
      among students emphasize the need to address student's concerns.

PMID- 16299606
TI  - Alteration of cyclic nucleotides levels and oxidative stress in saliva of human
      subjects with periodontitis.
AB  - Experimental findings suggest a protective role for cyclic nucleotides against
      induction of oxidative stress in saliva. Oxidative stress is a major contributor
      to the pathogenesis of inflammatory diseases. This study was conducted to
      evaluate salivary oxidative stress along with cGMP and cAMP levels in
      periodontitis subjects. cAMP and cGMP are second messengers that have important
      roles in salivary gland functions. Unstimulated whole saliva samples were
      obtained from periodontitis patients and age- and sex-matched healthy
      individuals. Saliva samples were analyzed for thiobarbituric reactive substances
      (TBARS) as a marker of lipid peroxidation, ferric reducing ability (total
      antioxidant power, TAP), and levels of cAMP and cGMP. Concentrations of cAMP and
      cGMP were reduced in the saliva of patients with moderate and severe
      periodontitis. Saliva of patients with severe periodontitis had higher TBARS and
      lower TAP than control subjects. The presence of oxidative stress and lower
      levels of salivary cGMP and cAMP in periodontitis are in association with disease
      severity.

PMID- 16299609
TI  - Oral health status in a population of Nigerian diabetics.
AB  - Oral manifestations of diabetes mellitus have been documented, but the effect of
      glycemic control on the oral tissues has been scantily reported. The oral health
      status of 65 metabolically controlled adult diabetic patients attending the
      Diabetes Clinic of Obafemi Awolowo University Teaching Hospitals Complex, Ile
      Ife, Nigeria, was prospectively assessed over six months and compared with that
      of 54 non-diabetic acting as controls. The mean duration of diabetes was 100.5+/
      85.1 months. The difference in periodontal status of the patients and control,
      assessed using the Community Periodontal Index of Treatment Needs (CPITN), was
      not statistically significant (p=0.07). The degree of hyposalivation between the
      two groups was, however, statiscally significant (p<0.05). No significant
      difference was observed in the altered taste, burning mouth sensation, angular
      cheilitis, glossitis, and stomatitis status of the two groups. We conclude, with
      adequate metabolic control, the oral health status of a diabetic may not be
      significantly different from that of a non-diabetic except for xerostomia. A good
      understanding of the interactions between systemic diseases and oral health is
      imperative for physicians and dental practitioners. The need for early detection
      and closer linkages between the dental and medical professions in managing
      diabetic patients is emphasized.

PMID- 16299610
TI  - Assessment of DMFT and enamel hypoplasia among junior high school children in
      Iran.
AB  - AIM: The main purpose of this study was to assess the prevalence and distribution
      of decayed, missing, and filled teeth (DMFT) and enamel hypoplasia in 12-year old
      students in junior high school in Iran. MATERIALS AND METHODS: This descriptive
      study was carried out in 2001 on 1,223 12-year old students, which were randomly
      selected in Yazd and Hadi-Shahr, Iran. A questionnaire was designed to record the
      status of the teeth along with the occupational and educational levels of
      parents. Data was analyzed using SPSS software, the Chi-square test, and analysis
      of variance (ANOVA). RESULTS: The mean DMFT score was 1.8 +/- 1.75 and 28.6% of
      the students were caries-free. There was no significant relationship between DMFT
      and the rate of dental caries with parents' education and occupation. The
      percentage of enamel hypoplasia was 32.7%. No statistically significant
      relationships were found between hypoplasia and DMFT with regard to gender. The
      relationship between enamel hypoplasia with DMFT score and dental caries was
      statistically significant. CONCLUSION: In the present study findings for DMFT
      scores in 12-year old junior high school children are higher than global
      standards according to the World Health Organization (WHO) references for the
      year 2000. There was a strong association between enamel hypoplasia and dental
      caries, and this subject suggests early diagnosis of enamel defects, health
      education programs, and suitable treatments should be emphasized in junior high
      school-aged children.

PMID- 16299611
TI  - Physical properties of four acrylic denture base resins.
AB  - Resistance to impact fracture and high flexural strength are desirable properties
      of denture base acrylics. The purpose of this laboratory study was to determine
      the Izod impact strength, the flexural strength, the flexural modulus, and the
      yield distance for four premium denture resins. Bar specimens 86 x 11 x 3 mm of
      Lucitone 199, Fricke Hi-I, ProBase Hot, and Sledgehammer Maxipack were fabricated
      following the manufacturer's instructions for heat processing. The bars were
      surface finished using silicon carbide paper to 600 grit. Ten specimens from
      three lots of each material were made (n=30). Flexural strength, flexural
      modulus, and yield distance were determined by testing the specimens to failure
      using a three-point test fixture. Izod impact strength was determined using an
      Izod tester on un-notched specimens generated from the flexural test (n=60).
      Analysis of variance (ANOVA) and post-hoc Tukey's test were used for statistical
      comparison of each property. There were significant differences in the physical
      properties among the denture acrylics tested. Lucitone 199 demonstrated the
      highest impact strength, flexural strength, and yield distance (p<0.05). Lucitone
      199 with an Izod impact strength of 5.5+/-1.2 N'm, a flexural strength of 99.5+/
      4.5 MPa, and yield distance of 9.9+/-0.76 mm exhibited statistically greater
      results than Fricki Hi-I, ProBase Hot, and Sledgehammer Maxipack. Fricki Hi-I
      with a yield distance of 7.3+/-1.1 mm was statically greater than ProBase Hot and
      Sledgehammer Maxipack. Fricki Hi-I, ProBase Hot, and Sledgehammer Maxipack were
      statistically similar for the Izod impact strength and flexural strength tests
      performed. ProBase Hot and Sledgehammer Maxipack yielded statistically similar
      results for all tests performed. Flexural modulus had an inverse relationship to
      the impact strength, flexural strength, and yield distance.

PMID- 16299612
TI  - Fetal alcohol syndrome: anthropometric and oral health status.
AB  - The purpose of this study was to analyze the anthropometric measures and oral
      health status of children with fetal alcohol syndrome (FAS) and compare them to
      matched controls. The sample of 90 cases (children diagnosed with FAS) and 90
      controls were matched for age, gender, and social class. The mean age of the
      cases was 8.9 years with the controls slightly older at 9.1 years. The results of
      the anthropometric measurements in respect of weight, height, and head
      circumference showed significantly lower values for the FAS children when
      compared to the controls. Several physical abnormalities described in children
      with FAS were seen in this study. Some of these abnormalities seen in the FAS
      children included deformities in the small joints of the hand, altered palmar
      creases, and malformation of the ears. The prevalence of enamel opacities between
      FAS and controls was not significantly different and averaged around 15% for both
      groups. More than three quarters of both the cases and the controls demonstrated
      the presence of plaque and almost two-thirds demonstrated gingival bleeding on
      probing. FAS patients had statistically significantly (p<0.001) more dentofacial
      anomalies than the controls. The mean decayed, missing, and filled teeth (dmft)
      score for the FAS sample was slightly higher, though not significantly different
      from that of the controls, and the decayed component (d) made up the largest part
      of the index in both groups.

PMID- 16299613
TI  - Effects of Nd: YAG laser irradiation on the adaptation of composite resins to
      root dentin.
AB  - One of the most important goals of the restoration of endodontically treated
      teeth with a composite resin post system is to achieve good adaptation of the
      composite material to dentin walls to prevent microleakage apically and
      coronally. In post core systems, to avoid microleakage between the dentin wall
      and resin material, laser irradiation may seem to be an alternative therapy for
      increasing adaptation quality. The aim of this study was to investigate the
      adaptation of a packable composite resin to lased root canal dentin when it was
      used as post material. Forty-five freshly extracted human teeth were selected and
      post spaces were prepared. The teeth were divided into three groups. In group 1
      the dentin of the post spaces were etched with 35% phosphoric acid, in group 2
      the dentin surfaces were irradiated with an Nd: YAG laser, and in group 3 the
      dentin surfaces were initially treated with the laser and then etched. The teeth
      of all groups were obturated with a bonding agent and composite. The groups were
      divided into two subgroups: a group for the scanning electron microscope (SEM)
      study and a group for the microleakage study. The lased group showed poor
      adaptation and more microleakage was detected (p<0.05; variance analysis). The
      laser beam and acid-etching showed no advantage compared to the acid-etching
      alone (p>0.05). The Nd: YAG laser irradiation adversely affects adhesion to
      dentin for using composite resin as a post material and does not constitute an
      alternative to acid-etching.

PMID- 16299614
TI  - The prevalence of dental caries among international students at U.S.
      universities.
AB  - Last year 572,509 international students studied at U.S. universities. The dental
      health of these students is as diverse as the countries from which they come.
      This paper discusses the known prevalence and causative factors of dental disease
      among these students, reported global variations in oral health, and barriers to
      receiving care faced by international students while in the U.S. The author
      recommends greater appreciation of the dental needs of this population by
      scholastic administrators and suggests further research to better quantify the
      dental needs of this population.

PMID- 16299615
TI  - Failures related to crowns and fixed partial dentures fabricated in a Nigerian
      dental school.
AB  - The purpose of this investigation was to document the failure rate and length of
      service of crowns and fixed partial dentures (FPDs) fabricated in a Nigerian
      dental school. The reasons for failure of the initial restorations and their
      length of service were also ascertained. Also, the numbers of retainers, pontics,
      and the types of restoration were recorded. Poor esthetics was the most frequent
      cause of failure, 66 units (40.5%); followed by fracture, 58 units (35.6%); and
      dental caries, 25 units (15.4%). These outcomes were contrary to findings
      previously reported in studies from western countries where dental caries was
      principally responsible for failures (22.0% to 38.0% of cases). The resin
      retained FPDs had the shortest mean years of service at 2.7 years, while the
      three-unit metal-ceramic FPDs had the greatest longevity at 8.6 years. The
      overall mean years of service for replaced restorations were 5.6 years. The study
      found a decrease in the mean years of service as the number of units in the fixed
      fixed partial dentures increased. This is in sharp contrast to previous reports
      where no relationship existed between length of service and the number of units
      in a FPD.

PMID- 16299616
TI  - Clinical management of the dental patient taking multiple drugs.
AB  - Adverse drug reactions (ADRs) occur often in elders often due to polypharmacy.
      Those over 65 currently comprise 13% of the population but consume approximately
      a third of all drugs prescribed. Increased care when prescribing certain drug
      classes and careful monitoring of the patient can prevent many ADRs. This article
      examines four questions that should be addressed when providing dental care for
      an older patient taking multiple medications. These include: (1) what are the
      medical conditions that necessitate the medications, (2) what impact do these
      medical conditions have on the provision of care, (3) what are the oral side
      effects of the medications, and (4) how will the patient's current list of
      medications alter the dentist's prescribing patterns for drugs used in dentistry?

PMID- 16299617
TI  - Delayed eruption of a mandibular primary cuspid associated with compound
      odontoma.
AB  - Although odontomas are considered to be a common type of odontogenic tumor, they
      rarely occur solely in the primary dentition. This case report presents an eight
      and a half-year-old-child with a compound odontoma located in the mandible, which
      caused the impaction of both primary and permanent canines.

PMID- 16299618
TI  - Retention of maxillary molars with Class III furcation involvement utilizing
      glass-ionomer: two case reports.
AB  - Advanced furcation invasion has long been a treatment dilemma for the clinician.
      The present two case reports used a glass ionomer restorative material as a
      barrier in the treatment of maxillary Class III furcation defects. One year
      follow-up results showed a reduction in tooth mobility and probing depths and no
      bleeding on probing with the use of the glass ionomer. These case reports offer
      another option in the treatment of a seemingly hopeless periodontally involved
      maxillary molar.

PMID- 16299619
TI  - Fiber-reinforced composite fixed partial denture to restore missing posterior
      teeth: a case report.
AB  - In patients refusing implant surgery for psychological reasons, when minimal
      tooth reduction is desired, a fiber-reinforced composite inlay fixed partial
      denture (IFPD) can be used to replace missing teeth. In comparison to other
      restorative systems this conservative approach carries a lower risk of pulp
      exposure and/or periodontal inflammation, maintaining the health of supporting
      tissues. The purpose of this case report is to describe the clinical procedure
      for fabricating an IFPD with a pre-impregnated glass fiber system and a hybrid
      composite. Fiber-reinforced composite, in combination with adhesive techniques,
      appears promising for an IFPD. Further clinical investigation will be required to
      provide additional information on this technique.

PMID- 16299620
TI  - Tobacco cessation for the dental team: a practical guide part II: evidence-based
      interventions.
AB  - Dental professionals are strategically placed to be the leaders in tobacco
      prevention and cessation as they provide preventive and therapeutic services to a
      basically healthy population on a regular basis. By expanding the dental exam,
      diagnosis, and treatment to include tobacco cessation, a potentially life saving
      element of care is added to an established service. In addition periodontal
      disease and the potential for oral cancer mandate the inclusion of tobacco
      cessation services into dental care. Though dental professionals are aware of the
      health issues associated with tobacco use, they often feel ill prepared or
      uncomfortable presenting patients with a clear cessation message. In this, the
      second of a two-part article, the purpose is to provide dental professionals with
      the evidence-based strategies necessary to provide effective tobacco cessation as
      a normal part of patient care.

PMID- 16299621
TI  - AAOMP case challenge: a firm palatal nodule.

PMID- 16299622
TI  - Management of renal problems in Australian general practice.
AB  - The BEACH program, a continuous national study of general practice activity in
      Australia, gives us an overview of consultations involving the management of
      renal problems. In this analysis, we have included renal failure,
      glomerulonephritis/nephrosis (all forms of nephritis and nephrotic syndrome),
      renal insufficiency, nephropathy (including diabetic and analgesic), and uraemia
      and nephrosclerosis grouped as 'other'. This synopsis provides a backdrop against
      which articles in this issue of Australian Family Physician can be further
      considered.

PMID- 16299623
TI  - Glomerulonephritis--management in general practice.
AB  - BACKGROUND: Glomerulonephritis (GN) is an important cause of both acute and
      chronic kidney disease, however the diagnosis can be difficult due to the
      variability of presenting features. OBJECTIVE: This article aims to develop a
      structured approach to the investigation of patients with markers of kidney
      disease, and promote the recognition of patients who need further assessment.
      Consideration is given to the importance of general measures required in the care
      of patients with GN. DISCUSSION: Glomerulonephritis is not an everyday
      presentation, however recognition and appropriate management is important to
      prevent loss of kidney function. Disease specific treatment of GN may require
      specialist care, however much of the management involves treatment of the
      associated complications such as oedema, achievement of target blood pressure and
      proteinuria reduction, and prevention and treatment of associated complications.

PMID- 16299624
TI  - Chronic kidney disease--management update.
AB  - BACKGROUND: Chronic kidney disease (CKD), defined as a glomerular filtration rate
      less than 60 mL/min/1.73 m2 and/or evidence of kidney damage for a period of at
      least 3 months, is an increasingly common, serious and under-recognised
      condition. A recent population study demonstrated that one in every 6 Australian
      adults has CKD (of which the vast majority are unaware). OBJECTIVE: This article
      aims to provide timely information to health professionals about how to classify
      and manage CKD. DISCUSSION: Management of CKD involves regular monitoring of
      cardiovascular and renal risk factors, identifying and treating common CKD
      complications, and avoiding medications that may worsen CKD. Early detection and
      timely appropriate management of CKD (especially with respect to blood pressure
      control) will substantially reduce kidney failure progression and cardiovascular
      risk by up to 50%.

PMID- 16299625
TI  - Automated reporting of GFR--coming soon to a laboratory near you!
AB  - BACKGROUND: Serum creatinine concentration is an unreliable and insensitive
      marker of chronic kidney disease (CKD). To improve CKD detection, Australasian
      guidelines have recently recommended that laboratories calculate and report an
      estimated glomerular filtration rate (eGFR) using the Modification of Diet in
      Renal Disease (MDRD) formula with every request for serum creatinine
      concentration. OBJECTIVE: This articles aims to provide timely information to
      health professionals about how to appropriately interpret and act upon eGFR
      reports. It also discusses the treatments shown to reduce renal and
      cardiovascular risk in CKD patients, and the indications for nephrologist
      referral. DISCUSSION: The accuracy and precision of eGFRs are reasonable in most
      adults in whom calculated values are ENTITY lt 60 mL/min/1.73 m2. However, eGFRs
      should be interpreted with caution in some settings (particularly patients with
      eGFRs ENTITY gt 60 mL/min/1.73 m2 and children). Automatic laboratory reporting
      of eGFR will enhance early detection of CKD, allow the timely institution of
      appropriate reno- and cardio-protective therapies, and better inform decisions
      regarding the prescription of renally excreted medications.

PMID- 16299626
TI  - Diabetic nephropathy--how might we prevent, retard, or cope with it?
AB  - BACKGROUND: Working life for most Australian doctors in adult practice is heavily
      involved with diabetes and its complications. The development of nephropathy is
      strongly intertwined with that of retinopathy, neuropathy and vasculopathy, and
      with reduced life duration and quality. What can we do at the coal-face of
      medical practice to prevent nephropathy occurring at all, to identify it early if
      it develops, and to maximally limit its impact after its emergence? OBJECTIVE:
      This article aims not to add to a literature bulging with comprehensive reviews
      of diabetic nephropathy, but to concisely summarise a useful evidence based
      approach to the evolutionary stages of the burgeoning problem of diabetic
      nephropathy. DISCUSSION: Until we can effectively prevent diabetes or achieve
      universal euglycaemia, our clinical focus will be on retarding the onset and
      progression of diabetic complications. Strategies dove-tail with those offering
      best cardiovascular protection, and are strongly supported by evidence that best
      outcomes are achieved when blood pressure targets are met, the renin-angiotensin
      system is blocked, good glycaemic control is achieved, and smoking is avoided.

PMID- 16299627
TI  - Childhood urinary conditions.
AB  - BACKGROUND: Urinary abnormalities are commonly detected in children and can be
      due to a wide range of conditions. OBJECTIVE: This article provides an overview
      of common urinary abnormalities presenting in childhood to assist general
      practitioners in planning further investigation and management. DISCUSSION: An
      initial assessment based upon a comprehensive history, examination and urinalysis
      should ensure that serious conditions are not overlooked and that unnecessary
      laboratory studies are not performed. Urinary dipstick testing should not be used
      to diagnose a urinary tract infection, but can often be used as a screen to
      exclude one. Isolated microscopic haematuria is only rarely a sign of significant
      kidney or urinary tract disease and nonpostural proteinuria is a more important
      diagnostic and prognostic finding that requires specialist assessment. In the
      majority of cases, the family can be reassured that the risk of significant
      kidney disease in asymptomatic children with minor urinary abnormalities is
      small.

PMID- 16299628
TI  - Proteinuria--CARI guidelines.
AB  - The CARI guidelines initiative is an Australian evidence based project that aims
      to provide high quality, evidence based clinical practice guidelines for the
      management of all stages of kidney disease. This article is a summary of the CARI
      guidelines on proteinuria with expert commentary by Mark Harris, Guidelines for
      preventive activities in general practice ('red book') Taskforce member.

PMID- 16299629
TI  - Cardiovascular issues of COX-2 inhibitors and NSAIDs.
AB  - BACKGROUND: Rofecoxib (Vioxx) was withdrawn from the market because of increased
      death from cardiovascular (CV) events. Other selective cyclooxygenase-2 (COX-2)
      inhibitors and traditional nonsteroidal anti-inflammatory drugs (NSAIDs) may
      share this risk, but to what extent is unclear. OBJECTIVE: This article reviews
      the available evidence using a PubMed search for increased CV risk with COX-2
      inhibitors and NSAIDs, explores possible mechanisms, and makes recommendations
      for their appropriate use in clinical practice. DISCUSSION: Rofecoxib, celecoxib,
      and the combination of valdecoxib and parecoxib have been found in prospective
      trials to increase CV risk. NSAIDs have also been found to be associated with
      increased CV risk in observational studies, but large randomised controlled
      trials with adequate follow up are required to further investigate this.
      Recommendations are to use drugs at lowest dose and for shortest duration
      possible. In patients with or at high risk for CV disease, COX-2 inhibitors are
      contraindicated. A traditional NSAID plus proton pump inhibitor may be used, but
      with caution.

PMID- 16299630
TI  - Ductal carcinoma in situ--management update.
AB  - This ninth article in our series on breast disease will focus on ductal carcinoma
      in situ of the breast--a proliferation of potentially malignant cells within the
      lumen of the ductal system. An overview of the management of ductal carcinoma in
      situ including pathology, clinical presentation and relevant investigations is
      presented, and the roles and dilemmas of surgery, radiotherapy and endocrine
      therapy are discussed.

PMID- 16299631
TI  - Patient education. Ductal carcinoma in situ.

PMID- 16299632
TI  - The ESSENCE of health care.
AB  - BACKGROUND: As community attitudes develop, health care costs spiral, and
      evidence accumulates, the health care system is steadily recognising the
      importance of moving toward more holistic and wellness based models. Such models
      have been shown to reduce costs and lead to better therapeutic outcomes.
      OBJECTIVE: This article discusses the ESSENCE model of health care and its
      application to clinical scenarios. DISCUSSION: The ESSENCE model is the basis for
      the Health Enhancement Program taught as core curriculum for all medical students
      at Monash University (Victoria). The model forms a useful structure upon which
      educational, preventive and therapeutic approaches can be built, and is readily
      adaptable for health professionals, individual patients, targeted groups,
      practice populations or public health campaigns.

PMID- 16299633
TI  - Diabetes and the skin. Part 2--leg ulcer.

PMID- 16299634
TI  - The RACGP Examination--changes from 1999-2004.
AB  - Promoting and maintaining the quality and standards of Australian general
      practice on behalf of the profession and the Australian community is The Royal
      Australian College of General Practitioners' central activity. An important part
      of this process is assessment of doctors wishing to attain Fellowship of the
      RACGP. For general practice registrars, the summative assessment process is the
      college examination. This article presents details of the assessment process,
      outlines changes in the RACGP Examination, and publishes its outcomes. This is
      the first in a series of three articles focussing on changes in the RACGP
      Examination, its candidature, analysis of results, and plans for future
      development.

PMID- 16299635
TI  - Failure to diagnose: renal disease.
AB  - Case histories are based on actual medical negligence claims, however certain
      facts have been omitted or changed by the author to ensure the anonymity of the
      parties involved. This article discusses a claim arising out of the failure to
      diagnose glomerulonephritis and examines the legal concepts of causation and loss
      of chance.

PMID- 16299636
TI  - The skill of the consultation--some observations on how not to do it.

PMID- 16299637
TI  - Research--getting started.

PMID- 16299638
TI  - My novice research experience.

PMID- 16299639
TI  - Screening for social anxiety disorder in first year university students--a pilot
      study.

PMID- 16299640
TI  - Depression after cardiac hospitalisation--the Identifying Depression as a
      Comorbid Condition (IDACC) study.
AB  - BACKGROUND: The Identifying Depression as a Comorbid Condition (IDACC) study
      aimed to identify depressive symptoms in hospitalised cardiac patients and
      support management of depression in general practice. OBJECTIVE: This post hoc
      analysis of the IDACC trial examines the effectiveness and practicality of
      different forms of communication between hospital psychiatric services and
      general practitioners. METHODS: We randomised 669 cardiac inpatients with
      depressive symptoms, identified with the Center for Epidemiological Studies
      Depression Scale (CES-D), to an intervention or usual care control group.
      Individual depression scores and depression management guidelines were sent to
      GPs of all intervention patients. Where possible, psychiatric advice was provided
      to the GP either by multidisciplinary enhanced primary care case conference or
      one-to-one telephone advice. RESULTS: Multidisciplinary case conferences were
      implemented for only 24% of intervention patients. General practitioners received
      individual telephone advice in 40% of cases, and 36% received written information
      only. The psychiatrist telephone advice resulted in a significant reduction in
      the proportion of patients with moderate to severe depression 12 months after
      cardiac hospitalisation (19% vs. 35%). DISCUSSION: Screening, combined with
      psychiatrist telephone advice to GPs, was simple to organise and effective in
      reducing depression severity after cardiac admission.

PMID- 16299641
TI  - Depression associated with combined oral contraceptives--a pilot study.

PMID- 16299642
TI  - Patient recruitment for a practice nurse study.

PMID- 16299643
TI  - Remote islands reveal rapid rise of southern hemisphere, sea debris.

PMID- 16299644
TI  - IVF and ICSI in male infertility: update on outcomes, risks, and costs.
AB  - Assisted reproductive technology with intracytoplasmic sperm injection (ICSI) is
      becoming an international panacea for couples struggling with infertility. The
      increasing popularity of these techniques and the data generated has given us a
      better understanding of the efficacy, consequences and costs of these procedures.
      There still remain many unanswered questions and controversies surrounding the
      use of IVF and ICSI. Increased experience, better refinement of these techniques
      and clearer indications for IVF and ICSI will inevitably minimize the risks
      associated with this procedure.

PMID- 16299645
TI  - [Statistical analysis of clinicopathologic characteristics of 1075 cases with
      colonic cancer].
AB  - OBJECTIVE: To investigate the clinicopathologic characteristics of colonic
      cancer. METHODS: All clinical data of surgical cases from hospital registry from
      1982 to 2002 were analyzed using SPSS 11.0 software. RESULTS: There were 1075
      patients with colonic cancer including 573 males and 502 females. The median age
      of the patients was 58 years. 90.8% of the patients aged over 40 years . The
      proportion of right colonic cancer was 64.7%. Well-differentiated and moderately
      differentiated adenocarcinoma accounted for 69.8%, and mucous carcinoma 13.6%.
      The proportions of early stage I, advanced stage II, III and IV cancer were 8.1%,
      45.0%, 26.5% and 20.3% respectively. The 5-, 10-year survival rates were 61.9%
      and 53.0% respectively. CONCLUSIONS: The risk for colonic cancer is significantly
      increased in patients over 40 years. The frequency of right colonic cancer is
      higher than that of left colonic cancer. The overall survival rate is high.

PMID- 16299646
TI  - [Protective efficacy and probable mechanism of ulinastatin in patients with
      gastrointestinal cancer undergoing adjuvant chemotherapy].
AB  - OBJECTIVE: To investigate whether ulinastatin can alleviate the side effect in
      patients with gastrointestinal cancer undergoing adjuvant chemotherapy,and to
      explore the probable mechanism of its protective efficacy. METHODS: Forty
      consecutive patients with gastrointestinal cancer who underwent surgical
      operations from May 2004 to October 2004 were recruited. The patients were
      randomly divided into therapeutic group and control group, receiving ulinastatin
      150,000 U per day or 250 ml hydrochloric sodium before chemotherapy for 5
      continuous days respectively. The prevalence of side effects and the levels IL-6
      and TNF-alpha were compared between the two groups. RESULTS: There were no
      differences in the clinicopathological characteristics between the two groups.
      The prevalences of white blood cell decline (41.2% versus 13.1%), pigmentation
      (23.5% versus 4.3%), baldness (17.6% versus 4.3%) were higher in the control
      group than those in therapeutic group (all P< 0.05). In therapeutic group, IL-6
      level was significantly decreased after ulinastatin treatment, but not in the
      control group while the levels of TNF-alpha were not changed in the both groups.
      CONCLUSION: Ulinastatin can reduce the common side effects of chemotherapy, and
      the mechanism may be associated with the decrease of IL-6.

PMID- 16299647
TI  - [Diagnosis and treatment of paraduodenal hernia: a report of 16 cases].
AB  - OBJECTIVE: To summarize the experience of diagnosis and treatment for
      paraduodenal hernia (PDH). METHODS: The clinical data of 16 cases with PDH
      surgically treated from 1962 to 2003 were analyzed retrospectively. RESULTS: The
      average age of the patients was 36 years old. There were 13 cases with left PDH
      (Landzerts hernia) and 3 cases with right PDH (Waldeyer's hernia). Ten patients
      usually had no symptoms, while acute abdominal pain occurred after full food in 3
      case and after vigorous movement in 13 cases respectively. X-ray revealed
      complete or incomplete intestinal obstruction in 12 cases, while ultrasonography
      and CT revealed dilated cystic jejunal loop between the pancreas and the stomach
      in 6 cases. Fourteen cases (87.5%) were misdiagnosed before operation. The
      hospital stay ranged from 10 to 13 days. All patients were followed up from 2 to
      4 years without recurrence. CONCLUSION: With high misdiagnostic rate, it is the
      key to perform exploratory operation for suspicious PDH.

PMID- 16299648
TI  - [Clinical analysis of mesenteric venous thrombosis:a report of 23 cases].
AB  - OBJECTIVE: To assess the early clinical diagnosis and treatment of mesenteric
      venous thrombosis (MVT). METHODS: Clinical data of 23 cases with MVT from January
      1994 to December 2003 were analyzed retrospectively. RESULTS: There were 17 males
      and 6 females, the age ranged from 19 to 74 years old with a mean age of 42
      years. Of them, 20 patients presented acute MVT. The main symptoms included
      abdominal pain and distention, nausea, vomiting, and bloody stool. The detect
      able rates of transabdominal color Doppler ultrasonography and CT for MVT were
      94.1% and 100% respectively. Nine of 11 (81.8%) patients were cured with non
      surgical management. Twelve patients underwent surgical treatments including
      resection of the infarcted bowel and open mesenteric venous thrombectomy with
      Fogarty catheter via a branch of mesenteric vein. The in-hospital mortality rate
      was 8.7%, and the postoperative morbidity rate was 33.3%, including ascites in 2
      patients and postprandial abdominal pain in other 2 patients. After follow-up
      from 2 months to nine years, 3 patients had MVT recurrence because of ceasing
      anti-coagulation treatment and 3 died of myocardial infarction, liver cancer and
      hepatic cirrhosis. CONCLUSION: Color Doppler ultrasonography and CT scanning are
      valuable diagnostic methods for MVT, and anticoagulation treatment and operation
      are effective managements.

PMID- 16299649
TI  - [Bowel control of anus-preserving operation for low rectal cancer in elderly
      patients over 75 years].
AB  - OBJECTIVE: To evaluate the bowel control of the anus-preserving operation for
      elderly patients over 75 years with low rectal cancer. METHODS: Thirty-nine
      elderly patients over 75 years with low rectal carcinoma (4-7 cm from anal verge)
      were treated during the study period. The patients were divided into different
      groups according to the surgical procedures and anastomotic locations. The bowel
      control and patients satisfaction were compared. RESULTS: The time of recovering
      normal defecation frequency was (9.8+/- 2.9) months. There were no differences in
      bowel control and anorectal manometric findings between the lower anastomosis
      group and super-lower anastomosis group, the lower anastomosis group and
      anorectal anastomosis group. The patients in anorectal anastomosis group
      displayed significantly better bowel control and anorectal manometric findings
      than those in the super-lower anastomosis group (P< 0.05). The time of recovering
      normal defecation frequency in colonic J-pouch-anal anastomosis group was (7.7+/-
      1.7) months, shorter than (10.6+/- 2.8) months in direct anastomosis group (P<
      0.01). The complication rate of I degree incontinence was 36.1%, but there was no
      difference between the two groups. The anorectal manometric findings were better
      in J-pouch-anal anastomosis group than those in direct anastomosis group (P<
      0.05). CONCLUSION: Colonic J-pouch-anal anastomosis for lower rectal carcinoma
      can significantly improve the bowel control in a short term without increasing
      the complication rate.

PMID- 16299650
TI  - [Reoperation for postoperative constipation recurrences of Hirschsprung disease].
AB  - OBJECTIVE: To summarize the causes and treatment experiences of postoperative
      constipation recurrences of Hirschsprung disease. METHODS: Clinical data of 37
      cases receiving operation again for postoperative constipation recurrences of
      Hirschsprung disease were collected. The recurrent causes, reoperation procedures
      and therapeutic efficacy were analyzed. RESULTS: Among 37 cases, the recurrent
      causes included insufficient resection of the intestine in 14 cases, co-existent
      intestinal neural hypogenesis in 6, gate syndrome in 5, and others in 12 cases.
      There was no postoperative death. Thirty-one cases (83.8%) were followed-up from
      6 months to 11 years. The defecation frequency was 1-2 times per day in 15 cases,
      one times per two days in 7, one times per three days in 6 cases. Two cases could
      defecate with the help of laxative purgatives. Nobody had incontinence.
      CONCLUSION: The main cause of postoperative constipation recurrences of
      Hirschsprung disease is insufficient resection of the intestine,and reoperation
      can get better results.

PMID- 16299651
TI  - [Expression and clinical significance of cancer-related gene MPS-1 in gastric
      cancer].
AB  - OBJECTIVE: To investigate the expression of cancer-related gene MPS-1 in gastric
      cancer and to evaluate its significance in clinical diagnosis and therapy.
      METHODS: The mRNA expression of MPS-1 was determined by polymerase chain reaction
      after reverse transcription (RT-PCR) in cancer tissues and adjacent non-cancerous
      tissues from 42 cases with gastric cancer. The expression levels of MPS-1 in 6
      gastric cancer cell lines (AGS, MKN-45, SGC 7901, KATO III, N-87 and SNU-1) were
      also determined by RT-PCR and Western blot. RESULTS: The MPS-1 mRNA was expressed
      in all tissues and cell lines. The mRNA expression level of MPS-1 in cancer
      tissues were 1.37+/- 0.87, significantly higher than 0.99+/- 0.67 in adjacent
      normal gastric mucous tissues (P< 0.01). The expression of MPS-1 was correlated
      with TNM stage (P< 0.05), but not with age, gender, tumor size and
      differentiation. The expression level of MPS-1 mRNA in the primary lesions was
      hig her in the patients with TNM stages III, IV than those with TNM stages I, II.
      Meanwhile, RT-PCR and Western blot showed the same results that MPS-1 expression
      was higher in the six gastric cancer cell lines as compared with that in the
      normal gastric cell line GES-1. CONCLUSION: The high expression of MPS-1 in
      gastric cancer indicates that MPS-1 might play an important role in gastric
      carcinogenesis,which may provide a new target in immunotherapy for gastric
      cancer.

PMID- 16299652
TI  - [Expression of cathepsin B and its clinical importance in colorectal cancer].
AB  - OBJECTIVE: To investigate the expression of cathepsin B (CatB) in colorectal
      cancer tissues and serum levels of CatB in patients with colorectal carcinoma and
      to study the association of CatB expression with lymph node and li ver
      metastasis. METHODS: Immunohistochemistry was used to detect CatB expression in
      tissues, and enzyme linked immunosorbent assay was applied to test CatB levels in
      peripheral vein blood in 83 patients with colorectal cancer. RESULTS: The
      expression rates of CatB in primary lesions, normal colon mucosa, lymph node
      metastases and hepatic metastases were 56.6%, 31.3%, 88.4%, 85.0% respectively.
      The positive rates of CatB in primary lesions, hepatic and lymph node metastases
      were higher than that in normal mucosa (chi (2)=45.6124, P< 0.01). The CatB
      expression rates in lymph node and hepatic metastases were higher than that in
      primary lesions chi (2)=11.5982, 4.3747, P< 0.05). The positive rate of CatB was
      higher in Dukes C and D tumors than that in Dukes A and B tumors (chi
      (2)=18.8871, 25.1650, P< 0.01), higher in poorly differentiated and mucous
      adenocarcinomas than that in well-moderately differentiated adenocarcinomas chi
      (2)=14.2338, P< 0.05). The mean serum level of CatB in 83 patients with
      colorectal cancer was (5.9+/- 2.9) ng/ml, higher than (2.3+/- 1.1) ng/ml in the
      controls of 30 healthy volunteers (t=6.6975, P< 0.01). The serum level of CatB in
      the patients with Dukes C, D stages were higher than that with Dukes A, B stages.
      CONCLUSIONS: Enhanced expression of CatB in colorectal cancer tissues is
      associated with tumor infiltration and metastasis. Monitoring serum CatB level in
      patients with colorectal cancer is important in the prediction and diagnosis of
      lymph node and hepatic metastasis,and valuable for evaluation of the therapeutic
      effect.

PMID- 16299653
TI  - [Effect of goblet cell in rat intestine on the restitution process of the gut
      barrier after hemorrhagic shock].
AB  - OBJECTIVE: To investigate the changes of the goblet cells in the intestine during
      the restitution process of the gut barrier after hemorrhagic shock. METHODS:
      Forty-nine Sprague-Dawley rats with body weight of 250-300 g were divided into
      control group (n=7) and experimental group (n=42). Rats in the experimental group
      was further divided into 6 groups (n=7 each) according to different time point at
      1, 3, 6, 12, 24, and 36 hours after hemorrhagic shock resuscitation. The
      specimens from ileum tissue were taken to observe the morphological chan ges of
      the intestinal mucosa. The number of goblet cells was determined by light
      microscope and/or electron microscope. The contents of trefoil factor family 3
      (TFF3) of goblet cells were examined using GC-9A gas chromatographic instrument.
      RESULTS: After hemorrhagic shock, mucosal epithelial injury was obvious in the
      small intestine. Tissue restitution was found after 3 hours, and mostly
      established after 12 hours. Following tissue restitution,the denuded mucosal
      surface was covered intensively by goblet cells. The number of goblet cells on
      the intestinal mucosa was reduced significantly from 243+/- 13 at 1 h to 157+/- 9
      at 24 h (r=- 0.910, P< 0.01), and returned to normal level at 36 h. In the
      experimental group, the content of TFF3 in the intestinal mucosa increased
      significantly at 12 hours, decreased, but was still higher at 24 hours (t=3.24,
      P< 0.05). CONCLUSIONS: The goblet cells play a key role in the restitution of
      intestinal mucosa. High expression of TFF3 may facilitate the intestinal mucosal
      restitution in the early phase.

PMID- 16299654
TI  - [Expression of inductive nitric oxide synthase and vascular endothelial growth
      factor in colonic carcinoma, and their effects on tumor angiogenesis].
AB  - OBJECTIVE: To investigate the expression of inductive nitric oxide synthase
      (iNOS) and vascular endothelial growth factor (VEGF), and their relations with
      clinicopathological parameters in colonic carcinoma. METHOD: Immunohistochemistry
      (streptomycin avidin-biotin peroxidase complex, SP) was used to detect the
      expression of iNOS, VEGF, collagen IV, FVIII Ag in colonic adenocarcinoma, and
      micro vessel density (MVD) was counted. RESULTS: The positive rates of iNOS and
      VEGF in colonic carcinoma were 76% and 80% respectively. The MVD in iNOS-positive
      carcinoma and iNOS-negative carcinoma were 37.0+/- 5.7 and 30.5+/- 4.9. The MVD
      in VEGF-positive carcinoma and VEGF-negative carcinoma were 39.5+/- 8.5 and
      30.7+/- 4.4. The expressions of iNOS and VEGF were positively correlated with
      MVD. The expression of VEGF was correlated with tumor invasion, differentiation
      and lymph no de metastasis, but not with patients age,sex and histologic type.
      CONCLUSION: The expression of iNOS and VEGF may play a role in the angiogenesis,
      metastasis and invasion of colonic carcinoma.

PMID- 16299655
TI  - [Relationship of vascular endothelial growth factor-C and lymphangiogenesis with
      the development and prognosis of colon cancer].
AB  - OBJECTIVE: To study the correlation of vascular endothelial growth factor-C (VEGF
      C) expression and lymphatic microvessel density (LMVD) with clinicopathological
      features and prognosis in colon cancer. METHODS: The expression of VEGF-C and
      VEGFR-3 was detected by immunohistochemical staining with monoclonal antibodies
      against VEGF-C and VEGFR-3 in 44 cases with primary colon cancer. LMVD was
      calculated. RESULTS: VEGF-C positive rate was 43.2% (19/44). VEGF-C expression
      was associated with tumor (P=0.003), lymph node metastasis (P=0.002), Dukes stage
      (P=0.001). The mean LMVD was 10.14+/- 4.19. LMVD was associated with lymph node
      metastasis (P=0.002), Dukes stage (P=0.001). LMVD in VEGF-C(+) group was (11.34+/
      4.83) higher than (9.24+/- 3.48) in VEGF-C(-) group, but there was no
      statistically significance between the two groups (P=0.105). The survival rate of
      the patients with positive VEGF-C was lower than that with negative VEGF-C
      (P=0.0225). The median survival time of the patients with LMVD(+) group was
      shorter than that with LMVD(-) (P=0.0036). Distant metastasis (P=0.0004),
      lymphatic metastasis (P=0.021) and LMVD (P=0.0469) were independent prognostic
      factors. CONCLUSIONS: VEGF-C and LMVD appear to be new prognostic factors for
      colon cancer. Furthermore, LMVD may be a new independent prognostic factor.

PMID- 16299656
TI  - [Study on gene expression profile difference in gastric cancer, pericancerous
      mucosa and normal gastric mucosa from the distant cutting margin by
      oligonucleotide microarray].
AB  - OBJECTIVE: To study the difference of gene expression profiles in gastric cancer
      (T), pericancerous mucosa (P) and the gastric mucosa from distant cutting margin
      (C), and to screen an associated novel gene in early gastric carcinogenesis by
      oligonucleotide microarray. METHODS: U133A (Affymetrix, Santa Clara, CA) gene
      chip was used to detect the gene expression profile difference in T, P and C,
      respectively. Bioinformatics was used to analyze the detected results. RESULTS:
      When gastric cancer was compared with normal gastric mucosa, 766 genes were
      found,with a difference of more than four times in expression levels, including
      530 up-regulated [Signal Log Ratio (SLR) > 2], and 236 down-regulated (SLR< -2).
      When P was compared with C, 64 genes were found, with a difference of more than
      four times in expression levels, including 50 up-regulated (SLR > 2), and 14 down
      regulated (SLR< -2). Compared with C, a total of 143 genes with a difference of
      more than four times in expression levels both in T and P tissues. Of the 143
      genes, 108 were up-regulated (SLR > 2), and 35 were down-regulated (SLR< -2).
      CONCLUSIONS: Gene chip can reveal 143 same genes both in pericancerous mucosa and
      gastric mucosa. These genes may be related to the carcinogenesis and development
      of early gastric cancer.

PMID- 16299658
TI  - [Effect of proto-oncogene protein c-met ribozyme transfection on biological
      behavior of gastric carcinoma cells].
AB  - OBJECTIVE: To explore the effect of c-met ribozyme transfection on biological
      behavior of gastric carcinoma cells. METHODS: U1/met292 plasmid containing c-met
      ribozyme gene was transfected into L2 subline of SGC-7901 gastric cell line, and
      the proliferative ability, distribution of cell cycle, protein expression of VEGF
      and c-met, as well as the potential of liver metastasis of the transfected
      subline were determined. RESULTS: There were no significant difference in
      proliferative ability, distribution of cell cycle between the transfected cells
      and the control cells. The protein expression of VEGF and c-met, as well as the
      liver metastatic potential significantly decreased in the transfected cells than
      those in the control cells (P< 0.05). CONCLUSION: The liver metastatic potential
      of c-met positive gastric cancer cells may be prevented by inhibiting c-met
      expression.

PMID- 16299657
TI  - [Expression of glutathione S-transferase-pi and DNA topoisomerase II alpha and
      their implications in colorectal carcinoma].
AB  - OBJECTIVE: To investigate the expression of GST-pi and Topo II-alpha, and their
      relationships with clinicopathological parameters in colorectal carcinoma.
      METHODS: The expression of GST-pi and Topo II-alpha were detected by avidin
      biotin-peroxide complex (ABC) method in tumor specimens, matched paratumor
      tissues from 60 cases with colorectal carcinoma and normal colonic tissues from
      15 cases. RESULTS: The expression rates of GST-pi and Topo II-alpha were 90.0%
      and 86.7% respectively in tumor tissues, significantly higher than those in
      matched paratumor tissues and normal tissues (P< 0.01). The expressions of GST-pi
      and Topo II-alpha were associated with cellular differentiation, Dukes stage and
      lymph node metastasis (all P< 0.01), but not with tumor size and histological
      type (all P > 0.05). The expression level of GST-pi was significantly higher in
      poorly differentiated tumors than that in well differentiated tumors. The
      expression level of Topo II-alpha in well-differentiated tumors were stronger
      than that in poorly differentiated tumors. CONCLUSIONS: The detection of GST-pi
      and Topo II-alpha expressions may be helpful to judge the malignant behavior,
      metastasis and prognosis in human colorectal carcinoma.

PMID- 16299659
TI  - [Statistical analysis of articles, citations and authors in Chinese Journal of
      Gastrointestinal Surgery from 2002 to 2004].
AB  - OBJECTIVE: To study the characteristics of of articles, citations and authors in
      Chinese Journal of Gastrointestinal Surgery(CJGS). METHODS: The data of
      articles,citations and authors of CJCS from 2002 to 2004 were collected and
      analyzed in terms of bibliometric parameters. RESULTS: There were 546 papers in
      CJCS during the past 3 years and project-funded papers accounted for 14.3%. The
      average number of articles per issue was 34; the average number of article per
      page was 0.44; the average publishing cycle of the articles was 7.52 months. The
      authors came from 28 provinces and Hong Kong SAR; the coauthor rate was 88.88%;
      the cooperation rate was 4.18. The papers with citation accounted for 92% and
      93.78% of the citations were from journals. The Prices indicator was 60.1%.
      CONCLUSION: Chinese Journal Gastrointestinal Surgery is a high quality academic
      journal with strong influence, and promotes the development and construction of
      gastrointestinal surgery in China.

PMID- 16299660
TI  - [Respiratory sleep disorders and cerebrovascular disease. Presentation].

PMID- 16299661
TI  - [Obstructive sleep apneas and arteriosclerosis].
AB  - The clinical importance of the obstructive sleep apnea syndrome underlies in its
      association with a major morbimortality principally in relation with adverse
      vascular events. Different physiopathologic mechanisms boosted by the recurrence
      of obstructive apnea episodes including alterations in several inflammatory
      mediators, metabolic factors associated with a dysfunction of vascular
      endothelium and the development of arterial hypertension would lead to an
      acceleration of the atherosclerotic process responsible in causality degree of
      the increment of cardiovascular disease in these patients.

PMID- 16299662
TI  - [Breathing disorders during sleep and the circadian rhythm of strokes].
AB  - Similar to myocardium infarct and sudden death, stroke presents a circadian
      rhythm with a maximum incidence of the beginning of the symptoms during the first
      morning hours. It is believed that this morning pick is secondary to
      haemodynamic, haemostatic and autonomic changes that happen during sleep, the
      sleep-awake transition and after wake up. About 25% of stroke, especially lacunar
      and atherothrombotic infarcts, occurs during night sleep. Usually, the symptoms
      are perceived for first time when the individual wakes up in the morning although
      stroke could have occurred long time before. These individuals are excluded from
      thrombolytic treatments and therapeutic trials. The patients that develop an
      ischemic stroke when sleeping presents more obstructive apneas during the acute
      phase of stroke than patients that suffer stroke during wakefulness. It is known
      that apneas are associated to oxyhemoglobin desaturations and to important
      haemodinamic changes and their treatment reduce cerebrovascular morbidity. These
      findings suggest that apneas, likely associated with other risk factors, can
      worsen or precipitate an ischemic stroke.

PMID- 16299663
TI  - [Brain haemodynamics in obstructive sleep apnea syndrome].
AB  - The obstructive sleep apnea syndrome (OSAS) is associated to a increased risk of
      cardiovascular diseases, including stroke. However, it is not known the cause of
      this last association. In this work the authors carry out a brief review of the
      theories that explain the relationship between OSAS and stroke and comment the
      potential alterations in cerebral hemodynamics of sleep apnea syndrome patients.
      The results of a recent case control study show that there are relevant
      differences in cerebral blood flow between OSAS patients and healthy subjects
      even in wakefulness. This fact could help to explain why OSAS causes a higher
      risk for suffering ischaemic strokes.

PMID- 16299664
TI  - [Patent foramen ovale and obstructive sleep apnea: their association and
      meaning].
AB  - The patent foramen ovale is a permanent aperture, similar to a floating membrane,
      remainder from fetal circulation. It can be easily diagnosed by transesophageal
      echocardiography and/or transcraneal Doppler with contrast. It is being described
      an increasing number of pathologies, where the presence of a patent foramen ovale
      can have pathologic significance. The paradoxical embolism considered a rare
      clinic curiosity, can be an underestimated cause of ischemic stroke. Patients
      with obstructive sleep apnea present a major prevalence of patent foramen ovale
      than normal population. In these patients can easily concur, at least
      theoretically, the basic criteria for paradoxical embolism. In this study, we
      revised the pathologic implications that can derive from this association.

PMID- 16299665
TI  - [Prevalence of breathing disorders during sleep in Spain].
AB  - Sleep-disordered breathing are frequent processes in Spain. Among them, the
      obstructive sleep apneas are the best known although not all studies are
      performed with the same diagnostic criteria with regard to the percentage of
      apneas and hypopneas per hour of sleep and the need to consider the presence or
      absence of clinic symptoms. After a reference to the biggest epidemiologic
      studies performed in different populations, the data of the major populational
      studies in our environs are analyzed.

PMID- 16299666
TI  - [The clinical importance of breathing disorders during sleep in the acute phase
      of strokes].
AB  - The temporal association between sleep-disordered breathing and the acute phase
      of cerebrovascular disease has been established. The question raised in this
      writing is about the clinic relevance of this association during the acute phase
      of stroke trying to answer questions like the relation with an excess of sleep
      disordered breathing, with the characteristics of stroke and its influence in
      prognosis, either at short and long term.

PMID- 16299667
TI  - [The importance of treatment for breathing disorders during sleep in stroke
      patients].
AB  - In the following exposure, we revised the possibility that the treatment of sleep
      disordered breathing with continuous nasal positive airway pressure could be
      potentially beneficial in three aspects: to control the sleep-disordered
      breathing as a risk factor for stroke, acting, in this sense, as primary
      prophylaxis; improving the prognosis of stroke, through conditioning a better
      functional recuperation or a lower mortality and finally through the control of
      recurrences, acting, in this sense, as secondary prophylaxis.

PMID- 16299668
TI  - [Prevalence of breathing disorders during sleep in patients with cerebrovascular
      disease].
AB  - More of the half of the stroke patients have sleep-disordered breathing. Among
      them, snoring and the obstructive sleep apnea syndrome (OSAS) have been the most
      studied. From different epidemiologic studies focused in finding a casual
      relationship between sleep-disordered breathing and stroke result evidences that
      at least establish that snoring and principally OSAS are a cause and consequence
      of stroke. The possibility to modify the respiratory disorder with treatment
      emphasizes the importance of this association.

PMID- 16299669
TI  - Comparative speed of kill of selamectin, imidacloprid, and fipronil-(S)
      methoprene spot-on formulations against fleas on cats.
AB  - The speed of kill of selamectin, imidacloprid, and fipronil-(S)-methoprene
      against Ctenocephalides felis infestations on cats for one month following a
      single treatment was evaluated. Eighty cats were randomly allocated so that there
      were 20 cats in four different treatment groups. On Days -2, 7, 14, 21, and 28,
      each cat was infested with 100 adult C. felis from the Kansas 1 flea strain.
      Following initial application only imidacloprid had caused a significant
      reduction in adult fleas on treated cats within 6 hours, but by 24 hours all
      three formulations had killed 96.7% of the fleas. At 7 days post treatment, all
      three formulations reduced flea populations within 6 and 24 hours by 68.4% and
      99.4%, respectively. At 21 and 28 days after treatment, none of the formulations
      killed significant numbers of fleas as compared to controls within 6 hours of
      infestation. At 28 days after treatment, selamectin, fipronil-(S)-methoprene, and
      imidacloprid had killed 99.0%, 86.4%, and 72.6% of the fleas within 48 hours of
      infestation, respectively. This study demonstrates that the speed of kill of
      residual flea products on cats decreases throughout the month following
      application. It also demonstrated that selamectin provided the highest level of
      residual activity on cats against the Kansas 1 flea strain.

PMID- 16299670
TI  - Guidelines for safe and effective use of NSAIDs in dogs.
AB  - NSAIDs are the most widely used analgesics in veterinary medicine, and all have
      some toxic potential. The most common adverse class effects are gastrointestinal,
      renal, hepatic, and coagulation disorders. When treating chronic pain associated
      with osteoarthritis, the effectiveness of NSAIDs can be enhanced by physical
      therapy, use of chondroprotective agents, certain adjunctive drugs, and diet and
      exercise to control weight. To treat acute perioperative pain, NSAIDs are more
      effective when used preemptively, in the context of balanced (multimodal)
      analgesia, and in well-hydrated patients with normal blood pressure and renal
      function. Screening and monitoring to identify high-risk candidates for NSAID
      treatment should include a physical examination and patient history,
      identification of preexisting diseases or conditions, obtaining baseline and
      periodic hematologic and clinical chemistry values, and ensuring that other
      NSAIDs or contraindicated drugs are not used concurrently. When switching a
      patient from one NSAID to another (when no side effects have been seen), a
      washout period of 5 to 7 days minimizes chances for adverse drug interactions.
      Informing clients of the potential adverse effects of NSAID therapy and signs of
      NSAID toxicity greatly increases the likelihood of safe use of this class of
      drugs.

PMID- 16299671
TI  - Comparison of bacterial organisms and their susceptibility patterns from otic
      exudate and ear tissue from the vertical ear canal of dogs undergoing a total ear
      canal ablation.
AB  - The purpose of this prospective study was to compare bacterial organisms and
      their susceptibility patterns from otic exudate and ear tissue from the vertical
      ear canal of six dogs with end-stage otitis undergoing a total ear canal
      ablation. Twenty-six organisms, 13 from the exudate and 13 from the tissue, were
      morphologically and biochemically similar, and their susceptibility patterns were
      compared. There were discrepancies for only 5 antibiotics for 4 organisms from 3
      dogs. Culture of otic exudate from the vertical ear canal of dogs with chronic
      end-stage otitis externa provides an accurate reflection of the bacterial species
      present and the antimicrobial susceptibility patterns of these infections.

PMID- 16299672
TI  - Preventing parasites in cats.
AB  - The monthly administration of broad-spectrum heartworm medications can
      effectively prevent a variety of internal and external parasitic diseases in
      cats. Although not every parasite can be stopped, many of the common feline
      parasites are susceptible to these agents. This article discusses the
      epidemiology and prevention strategies for those parasites that can be controlled
      by the administration of ivermectin, milbemycin oxime, or selamectin, either
      alone or in conjunction with an external parasiticide.

PMID- 16299673
TI  - Scintigraphic, radiographic, and thermographic appearance of the metacarpal and
      metatarsal regions of adult healthy horses treated with nonfocused extracorporeal
      shock wave therapy--a pilot study.
AB  - Nonfocused extracorporeal shock wave therapy (ESWT) treatment protocol is
      commonly used in veterinary practice. This study investigated the effects of four
      nonfocused ESWT treatments, given 2 weeks apart, on bone radiopharmaceutical
      uptake and radiographic and thermographic appearance in the metacarpal and
      metatarsal regions in six adult untrained horses. There were no measurable
      treatment effects determined by thermography (daily), scintigraphy (at 2-week
      intervals), and radiography (before study initiation and at study completion)
      between treated and control limbs. It was concluded that no gross evidence of
      bone remodeling is detectable by conventional clinical assessment when nonfocused
      ESWT is applied to healthy equine metacarpal or metatarsal bone.

PMID- 16299674
TI  - Histopathological atlas of renal diseases: light chain deposition disease.
AB  - Monoclonal diseases of B-cell lineage, often referred to as plasma cell
      dyscrasias, are characterized by abnormal and uncontrolled proliferation of a
      single clone of B cells at different maturation stages, with a more or less
      marked differentiation to immunoglobulin (Ig)-secreting plasma cells. Thus B-cell
      proliferation is usually associated with the production and secretion in blood of
      a monoclonal Ig or a fragment thereof. An ominous consequence of secretion of
      monoclonal Ig products is their deposition in tissue. These proteinaceous
      deposits can take the form of casts (in myeloma cast nephropathy), cristals (in
      myeloma-associated Fanconi's syndrome), fibrils (in light-chain [LC]
      amyloidosis), or granular precipitates (in monoclonal Ig deposition disease
      [LCDD]).

PMID- 16299675
TI  - Factors predicting progression of IgA nephropathies.
AB  - The difficulties in defining the natural history of primary IgA nephropathy
      (IgAN) depend upon the pre-selection of patients for renal biopsy, a true
      individual variability - ranging from asymptomatic to rapidly progressive forms -
      as well as the use of different classifications of the renal lesions and
      statistical analyses sometimes carrying incorrect modalities. Long-term natural
      history studies have demonstrated that the rate of progression has an extremely
      wide range, from 5 to 25% after 10 years and 25-50% at 20 years, and complete
      remission is reported as well in 5 to 30% of cases. A geographic variability has
      been confirmed in a tri-continental study, explainable only partly by the earlier
      referral. Among the factors predicting progression, the more frequent in cohorts
      showing worse actuarial survival at 10 years are those associated with the
      advanced phases of renal damage, as increased creatinine level, arterial
      hypertension and nephrotic range proteinuria. A multivariate statistical approach
      showed the relevance of proteinuria during follow-up (percent duration of massive
      proteinuria or proteinuria at 1 year) more than proteinuria at the onset. Mean
      blood pressure value (MAP) and proteinuria during follow-up were independent
      predictors of end-stage CKD. Note the predictive value of severe microscopic
      hematuria in several studies. As far as histological features are concerned,
      strong independent predictors of progression at Cox multivariate analysis are the
      severity of glomerular sclerosis and interstitial fibrosis. The presence of
      crescents was a risk factor in almost all studies at univariate analysis, but did
      not maintain a significant predictor value at multivariate analysis. Conversely
      the association between crescents and tuft adhesions, possibly resulting from
      previous segmental necrosis, was found to be a significant risk factor. The
      extent of mesangial proliferation and parietal expansion of deposits was not
      significantly associated to unfavourable prognosis at multivariate analysis. The
      analysis of risk factors for progression of IgAN related to Henoch-Schoenlein
      purpura (HSP) failed to demonstrate any prognostic value for the presence and
      severity of extra-renal signs of vasculitis or presence of triggering factors. At
      multivariate Cox analysis, age and mean proteinuria during follow-up were
      powerful independent prognostic predictors. Proteinuria at baseline was not
      significantly related to renal progression, nor were hypertension or impaired
      renal function at onset. It is of interest that data at onset and at renal biopsy
      (renal function impairment, hypertension, nephrotic-range proteinuira) were not
      significantly related with renal detrimental progression. Neither had prognostic
      value the finding of crescents involving up to 75% of glomeruli.

PMID- 16299676
TI  - Mediators of inflammatory and ischemic renal damage: the role of neoangiogenesis.
AB  - Neoangiogenesis is at the forefront of research in a number of fields that are of
      interest to the nephrologist, ranging from the development of the kidney and
      glomerulus to microvascular injury and its repair. The molecular mechanisms have
      recently been elucidated to a considerable extent. They are relevant for
      understanding the link between endothelial cells and podocytes, which underlie
      the glomerular barrier function. For reasons poorly understood capillarogenesis
      is defective in renal failure.

PMID- 16299678
TI  - New immunosuppressive therapies in renal transplantation: monoclonal antibodies.
AB  - Remarkable advances in understanding the mechanisms of immune recognition and
      allograft rejection have been made in the past few years, leading to the
      development of innovative immunosuppressive strategies in the field of renal
      transplantation. Monoclonal antibodies (mAbs) have emerged as a new class of
      immunosuppressive agents, which appear to be effective (in both the treatment and
      the prevention of acute rejection) and well-tolerated in renal transplant
      recipients. The highly specific effects of these drugs make them less toxic than
      the oral long-term maintenance agents such as corticosteroids and the calcineurin
      inhibitors. Some of these mAbs have already confirmed their efficacy in
      preventing acute rejection in clinical phase III studies, and are now part of the
      well-established immunosuppressive regimens; these are the anti-CD25 mAbs
      (basiliximab and daclizumab). Other recently developed mAbs, like anti-CD52
      (Campath-1H), anti-CD20 (rituximab), anti-LFA-1, anti-ICAM-1 and anti-tumour
      necrosis factor (TNF)-alpha (infliximab), are currently being tested, and show
      encouraging immunosuppressive potential. Blocking either the binding of cell
      surface molecules or intracellular signal transduction, these mAbs could become
      an effective method to promote the holy grail of solid-organ transplantation,
      antigen-specific tolerance.

PMID- 16299677
TI  - Neurological complications in kidney transplant recipients.
AB  - Neurological complications are frequent in renal transplant recipients and may
      largely contribute to morbidity and mortality. The postransplant neurological
      complications may be categorized into five areas: 1) Immunosuppressive
      medications, 2) stroke, 3) peripheral neuropathies, 4) infection, and 5)
      malignancies. A number of complications are directly caused by the neurotoxicity
      of immunosuppressive agents. Calcineurin-inhibitors may cause mild symptoms, such
      as tremors and paresthesia, or severe symptoms, such as disabling pain syndrome
      and leukoencephalopathy. Severe neurological syndromes may also be caused by the
      monoclonal antibody OKT3. Stroke may occur in about 8% of renal transplant
      patients. It may be favored by hypertension, diabetes, and accelerated
      atherosclerosis which may be acquired during dialysis or after transplantation.
      Peripheral mononeuritis and polyneuritis may also occur. An acute femoral
      neuropathy may occur in about 2% of patients as a result of nerve compression
      after operation. Guillain-Barre syndrome may also develop, triggered in some
      cases by cytomegalovirus (CMV) or Campylobacter jejuni infection. Lymphomas are
      the most frequent brain tumors. They are usually associated to a Epstein Barr
      virus (EBV) infection and are more frequent in patients who received an
      aggressive immunosuppressive therapy. Infection represents the most frequent
      neurological complication. Acute meningitis usually caused by Listeria
      monocytogenes, subacute and chronic meningitis caused by Cryptococcus neoformans,
      focal brain infection caused by Aspergillus fumigatus, Toxoplasma gondii or
      Nocardia asteroids, and progressive dementia caused by polyoma J virus or other
      viruses are the most frequent types of neurological infections.

PMID- 16299679
TI  - The genetic background of uremic secondary hyperparathyroidism.
AB  - Many studies have shown how gene mutations and genetic polymorphisms could
      influence secondary uremic hyperparathyroidism (HPTH), modulating parathyroid
      (PT) function and hyperplasia. Parathyroid hormone (PTH) gene expression and
      hormone secretion is regulated mainly by serum calcium, with a post
      transcriptional effect, and by vitamin D with a transcriptional effect. PT cells
      retain the ability to proliferate and to apoptose. Hyperphosphatemia,
      hypocalcemia and vitamin D deficiency all stimulate PT cell proliferation. In the
      early stage of chronic uremia, PT proliferation is polyclonal, as in diffuse
      hyperplasia, whereas nodular hyperplasia growth is monoclonal with an
      increasingly recognized genetic background. HPTH has been associated with a
      number of familial diseases, such as multiple endocrine neoplasia-type 1 (MEN1),
      multiple endocrine neoplasia-type2A (MEN2A), neurofibromatosis type1 (NF1) and
      HPTH with multiple ossifying jaw fibromas (HPT-JT Syndrome). The genes involved
      in these diseases have been also investigated in secondary HPTH (sHPTH).
      Moreover, in sporadic and secondary uremic HPTH, clonal rearrangement and/or
      oncogene overexpression, gene deletions and tumor suppressor gene inactivation
      have been reported. However, each condition shows different patterns of genetic
      abnormalities. Finally, PT function modulation by genetic polymorphisms of
      vitamin D and calcium receptors and of the PTH gene is reviewed.

PMID- 16299681
TI  - Native renal biopsies: complications and glomerular yield between radiologists
      and nephrologists.
AB  - Kidney biopsies have been taken over by radiologists at many institutions. This
      tendency for radiology referral by nephrologists has two main drawbacks: 1) No
      follow-up care from the physician performing the procedure and 2) Loss of
      required procedure training for nephrology fellows. This study assesses for
      differences in glomerular yield and immediate procedure-related complications
      between radiology-performed (RP) and nephrology-performed (NP) percutaneous
      native kidney biopsies at our institution for an 11-month period. All biopsies
      were done with real time ultrasound guidance. Further analysis was done to look
      for any correlation between the number of needle insertions ("passes"), needle
      size and procedure-related complications (graded on a score from 0-4). A total of
      37 native kidney biopsies were performed during the study period. Fourteen
      biopsies (38%) were performed by radiology while a nephrology fellow performed 23
      biopsies (62%). The mean glomerular count for RP biopsies was 15+/-10 and for NP
      16+/-11 (p=ns). The number of passes ranged from 1-5 in the RP group with a total
      of 33 passes in 14 patients (mean 2.36 passes/patient). Passes ranged from 1-6 in
      the NP group with 57 passes in 23 patients (mean 2.48 passes/patient). Mean
      complication scores were similar in both groups. However, severe complications
      (score 4) were significantly lower in nephrology fellow performed biopsies (p =
      0.001). Despite similar pre-biopsy risk assessment and treatment protocols with
      real-time ultrasound guidance of all biopsies, these results show no
      statistically significant differences in glomerular yield or overall complication
      scores but did demonstrate a significantly higher rate of severe complications
      (score 4) in the RP performed biopsies. Nephrology fellows perform native kidney
      biopsies at a level equal to or superior to radiologists.

PMID- 16299680
TI  - Effects of nitric oxide on gentamicin toxicity in isolated perfused rat kidneys.
AB  - BACKGROUND: There have been many studies in recent years concerning the role of
      nitric oxide (NO) in acute renal failure (ARF). In this study, the effects of the
      inhibition or the induction of NO synthase (NOS) on gentamicin-induced ARF was
      investigated in isolated perfused rat kidneys. METHODS: Kidneys from male Sprague
      Dawley rats were perfused in situ for 90 min. Perfusion was conducted in the
      presence of inulin (60 mg/dL in perfusion buffer) as a glomerular filtration rate
      (GFR) marker. Six groups (total: 42 rats) were studied: group 1, controls with no
      treatment; group 2, L-arginine (2 mM in perfusate); group 3, L-nitro-arginine
      methyl ester (L-NAME, 0.1 mM in perfusate); group 4, gentamicin (GM, 0.5 mg/mL in
      perfusate); group 5, GM + L-arginine (same dose as groups 2 and 4) and; group 6,
      GM + L-NAME (same dose as groups 3 and 4). Cell injury was assessed by measuring
      N-acetyl-beta-D-glucosaminidase (NAG), lactate dehydrogenase (LDH) and alkaline
      phosphatase (ALP) activity in urine. RESULTS: L-arginine prevented, whereas L
      NAME enhanced, GM-induced enzyme release and GFR reduction. Histological studies
      showed that GM-treated kidneys had clear signs of tubular damage and this damage
      was increased by simultaneous L-NAME and GM administration. CONCLUSION: This
      study suggests that NO formation could prevent the GM-induced nephrotoxicity in
      this ARF model.

PMID- 16299682
TI  - Serum cystatin C and urinary enzymes as screening markers of renal dysfunction in
      diabetic patients.
AB  - BACKGROUND: In clinical practice, the assessment and follow-up of early renal
      dysfunction is important in diabetic nephropathy. Therefore, this study was
      designed to determine whether the serum cystatin C (Cys C) and activities of some
      tubular enzymes could be used as screening markers for renal dysfunction in
      diabetic patients. METHODS: Serum Cys C levels and urinary activities of N-acetyl
      b-D-glucosaminidase (NAG), alkaline phosphatase (ALP) and lactate dehydrogenase
      (LDH) and whole blood glycolyse hemoglobin (HbA1C) were measured in 56 diabetic
      patients and 20 healthy subjects (controls). The results were compared with serum
      creatinine (Cr) and creatinine clearance (CCr), which were measured and estimated
      with the Cockcroft-Gault formula (CCG) and 24-hr urine microalbuminuria (MAU). We
      examined the influence of albuminuria, HbA1C and CCr levels of patients on the
      levels of the analyzed parameters. Sensitivity and specificity for the diagnosis
      of renal impairment were calculated by a receiver operating characteristics (ROC)
      curve for serum Cys C, Cr and urinary enzymes. RESULTS: In normoalbuminurics,
      only serum Cys C levels and urinary NAG activities were found elevated as
      compared to controls. In addition to the elevation of serum Cys C levels and
      urinary activities of NAG, urinary ALP and LDH activities were also found
      elevated in microalbuminurics. Serum Cys C levels and urinary NAG, ALP, LDH
      activities started to increase above the normal range when CCr declined and while
      serum Cr was in the normal range in patients with 50<CCr<80 (grade 2 group).
      Moreover, these parameters in patients with good metabolic control were
      significantly lower than in patients with poor metabolic control. There was a
      significant positive correlation between serum Cys C, urinary NAG, LDH, ALP
      activities and serum Cr levels. However, there was an inverse correlation between
      serum Cys C, urinary NAG, LDH, ALP and CCr and CCG in diabetic patients. The ROC
      plot indicated that serum Cys C and urinary NAG and ALP had higher sensitivity
      than serum Cr and met the criteria for detecting glomerular and tubular
      dysfunction as screening tests for early diagnosis of diabetic nephropathy.
      CONCLUSION: This study demonstrated that measuring serum Cys C levels and urinary
      NAG, ALP and LDH activities could be useful as screening markers to follow-up
      glomerular and tubular dysfunction in diabetic patients.

PMID- 16299683
TI  - One year course of oral sulodexide in the management of diabetic nephropathy.
AB  - BACKGROUND: Diabetic nephropathy is a multifactorial diabetic complication whose
      long-term consequences involve chronic renal insufficiency and increased rate of
      cardiovascular death. Besides oxidative stress, and hemodynamic changes,
      glycosaminoglycans (GAGs) are an additional component implicated in the onset of
      glomerular abnormalities. GAG replacement therapy was envisaged in the nineties
      for the treatment of diabetic nephropathy and sulodexide is the most extensively
      investigated GAG to reduce albuminuria in diabetic patients. METHODS: In this
      study we have evaluated the effect of a long-term course of oral sulodexide at a
      moderate dosage in the treatment of patients affected by diabetic nephropathy.
      Thirty patients with type 1 and 2 diabetes mellitus (DM) have been treated with
      50 mg/ daily oral sulodexide for 12 months while thirty matched diabetic patients
      constituted the control group. All the patients attended monthly visits and
      controls of biochemical and metabolic parameters. RESULTS: At 12 months
      albuminuria was greatly reduced in patients treated with sulodexide and increased
      in the control group (260% and +29% vs baseline, respectively; p = 0.0001). The
      drug appeared active in both type 1 and type 2 diabetes and in both micro- and
      macroalbuminuric patients. No change in metabolic control and no systemic side
      effects were reported. CONCLUSIONS: In our diabetic patients sulodexide therapy
      has been proven to greatly reduce albuminuria, and to have the potential to delay
      progression from incipient to overt nephropathy.

PMID- 16299684
TI  - Disordered balance of IgA subclass production in the tonsils of some IgA
      nephropathy patients.
AB  - BACKGROUND: There are reports concerning the relationship between tonsillectomy
      and immunoglobulin A nephropathy (IgAN). Two reports on the biochemical analysis
      of over-produced IgA1 from IgAN patients were recently published. On the other
      hand, histochemical analysis of tonsillar tissue indicated the disordered balance
      in IgG and IgA producing cells and in the IgA subclass producing cells in IgAN
      patients. METHODS: IgA in tonsillar extracts and serum was separated into passed
      fraction (IgA2) and bound fraction (IgA1) by a jacalin-agarose column.
      Isoelectric focusing (IEF) analysis was carried out using an IPGphor instrument.
      The IgA content in each sample was analyzed by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: The IgA1/IgA2 ratio of the tonsillar extracts from controls and
      IgAN patients was compared. The ratio distribution indicated statistically
      significant differences. The mean ratio for the control tonsil was 61/39.
      However, the ratio from eight out of thirty-two IgAN patients exhibited a higher
      value than the mean + 2SD (standard deviation) of the controls. Among them, three
      patients exhibited 92/8. Meanwhile, the ratios for serum by this method were
      close to the previously reported 89/11. There were no differences in the IgA1 IEF
      profile between the representative lowand high-IgA1 producing patients.
      CONCLUSIONS: This is the first report concerning IgA subclass distribution in
      tonsillar tissue. The ratio 61/39 for tonsillar IgA differ from the value (>90%
      of IgA1) in the previous histochemical report. The value is similar to the
      previous report for colostrum, whole saliva, jejunal fluid and bronchial fluid.
      The IgA1/IgA2 ratio distribution in the tonsillar extracts from the patients with
      chronic tonsillitis is significantly different from that of the IgAN patients.

PMID- 16299685
TI  - Interleukin-6 (IL-6) -174 G/C polymorphism in familial Mediterranean fever
      patients with and without amyloidosis.
AB  - Familial Mediterranean fever (FMF) is a recessive disorder characterized by
      attacks of fever and inflammation. A sustained inflammatory reaction is observed
      in the disease course, and cytokine levels such as interleukin (IL)-1, IL-6 and
      tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between
      the attacks. In this study, we investigated the role of the functionally
      important IL-6 -174 G/C polymorphism in the clinical outcome of FMF and
      amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90
      healthy controls were studied. The genotype distributions and allele frequencies
      of the patients and the controls were found to be similar, and the differences
      between the groups were not statistically significant. The results show that IL-6
      -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase
      observed in cytokine levels during and between the attacks is more likely due to
      the inflammatory nature of the disease.

PMID- 16299686
TI  - Anti-renin-angiotensin-system drugs and development of anemia in chronic kidney
      disease.
AB  - BACKGROUND: A variable inhibition of erythropoiesis has been reported in uremic
      patients with renal anemia receiving anti-renin-angiotensin-system (RAS) drugs
      (angiotensin-converting-enzyme inhibitors, and angiotensin-receptor-antagonists).
      The time to development of renal anemia before dialysis is still unknown.
      METHODS: A retrospective cohort study (1 to 15 years) on records of 327 out
      patients (217 males, 110 females) without anemia and with chronic renal
      insufficiency (creatinine clearance 16 to 75 mL/min) was conducted to estimate
      the time to development of renal anemia (Hb < 11.5 g/dL in females and Hb < 12.5
      g/dL in men), and the time to decrease of Hb by 1 and 2 g/dL or more,
      irrespective of anemia development. Two treatment groups were analyzed: 142
      patients with, and 185 without anti-RAS drugs. RESULTS: Median survival time to
      development of anemia was 81 months, 59 months to the loss of Hb > 1 g/dL, and 94
      months for the loss of Hb > 2 g/dL. Anemia developed significantly earlier in
      patients with initial Ccr < 40 mL/min and in those with initial Hb < 14 g/dL. In
      the multivariate analysis (Cox model), male gender, Ccr < 40 mL/min, and Hb < 14
      g/dL, in increasing order of relative risk, significantly contributed to
      prediction of anemia development without any influence of the treatment with anti
      RAS drugs. The same results were obtained considering survival to the loss of
      either Hb > 1 g/dL or Hb > 2 g/dL. CONCLUSIONS: Development of renal anemia in
      mild to severe chronic kidney disease is not influenced by treatment with anti
      RAS drugs.

PMID- 16299687
TI  - Risk factors and underlying cardiovascular diseases in incident ESRD patients.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality and
      morbidity in dialysis patients. The aim of this study was to evaluate the
      prevalence of cardiovascular risk factors and of CVD on admission to
      hemodialysis. METHODS: Data were collected in 31 Italian clinics belonging to a
      clinic network using a prospective database (EuCliD), the main purpose of which
      is the support of quality assurance. Six hundred and thirty-six patients, mean
      age 63.9+/-15.4 years, admitted between January 1, 2000 and September 30, 2003,
      were separated into two groups on the basis of presence of CVD and observed for a
      median follow-up period of 16 months. RESULTS: In the CVD group, patients were
      significantly older and the percentage of diabetics and smokers was significantly
      greater than in the CVD-free group. There were no significant differences between
      the groups in term of uremia-related risk factors. According to logistic
      regression analysis evaluating the impact of traditional and nontraditional
      cardiovascular risk factors, only smoking habit (OR 1.87, 95% CI 1.25-2.79) and
      diabetes (OR 1.87, 95% CI 1.19-2.95) were associated with a higher relative risk
      for the presence of CVD at baseline. At the time of admission, CVD was present in
      27% of patients. The following de novo development of CVD was observed:
      hypertensive disease (0.28 new cases/100 pt-years), ischemic heart disease (0.71
      new cases/100 pt-years), other forms of heart disease (1.57 new cases/100 pt
      years), disease of arteries, arterioles, etc. (1.85 new cases/100 pt-years) and
      cerebrovascular disease (0.71 new cases/100 pt-years). The rate of developing de
      novo CVD events was 3.70 per 100 patient-years. CONCLUSIONS: The prevalence of
      cardiovascular risk factors is already high at admission to dialysis. Despite the
      care provided to dialysis patients, a significant proportion of patients develop
      de novo CVD.

PMID- 16299688
TI  - Global assessment of serum antioxidant status in hemodialysis patients.
AB  - BACKGROUND: Since chronic renal failure (CRF) was described as a state of
      oxidant/antioxidant imbalance augmented after hemodialysis (HD) initiation, we
      assessed the total antioxidant activity and single antioxidants in sera from
      uremic patients dialyzed or not, compared to subjects with normal renal function.
      METHODS: Serum total antioxidant activity (TAA--measured as Trolox equivalent
      antioxidant capacity; mmol/L), total plasma free thiols (Pt-SH; micromol/g
      protein), albumin (g/dL) and uric acid (mg/dL) were determined in 19 hemodialyzed
      patients, 15 CRF non-dialyzed patients (serum creatinine (Cr) = 4.4 +/- 2.7
      mg/dL) and in 16 healthy controls. The "antioxidant gap" (mmol/L), as a measure
      of the combined activity of plasma antioxidants other than albumin and uric acid,
      was calculated. RESULTS: TAA and the "antioxidant gap" were higher in HD patients
      (1.21 +/- 0.12 vs. 0.96 +/- 0.13 in the non-HD group, p<0.001, and vs. 0.9 +/-
      0.14 in controls, p<0.001, respectively, for TAA; 0.46 +/- 0.15 vs. 0.2 +/- 0.15,
      p<0.001, and vs. 0.21 +/- 0.16, p<0.001, respectively, for residual antioxidant
      activity). However, no differences existed in major plasma antioxidant levels
      (albumin and uric acid) among uremic patients, hemodialyzed or not. Pt-SH were
      reduced in nondialyzed patients as compared to controls (6.21 +/- 1.1 vs. 7.33 +/
      0.83, p=0.002), but were elevated in HD patients (11.9 +/- 1.1). CONCLUSIONS:
      These results suggest that HD patients appear to have improved plasma antioxidant
      status, hyperuricemia not being the sole contributor. Therefore, it seems
      reasonable to speculate that other antioxidants (thiols or some as yet
      unrecognized substances) could also be contributors. However, more reliable
      assays for extracellular antioxidant defense evaluation are required to validate
      this hypothesis.

PMID- 16299689
TI  - Serum creatinine and coronary mortality in the elderly with normal renal
      function: the CArdiovascular STudy in the ELderly (CASTEL).
AB  - BACKGROUND: Elevated serum creatinine (SCr) levels have been associated with
      increased mortality. Aim of this study is to evaluate whether SCr independently
      predicts coronary heart disease (CHD) mortality in a population of elderly with
      SCr values within the normal range. METHODS: Three thousand two hundred and fifty
      seven men and women aged > or = 65 years were recruited in the population-based
      frame. Historical and clinical data, blood tests and 12-year fatal CHD events
      were recorded. SCr and creatinine clearance (Crcl) were divided into tertiles
      and, for each tertile, gender-specific adjusted relative risk (RR) with 95%
      confidence intervals (CI) for CHD mortality was calculated. RESULTS: Both SCr and
      Crcl independently predicted CHD in men but not in women. In men CHD mortality
      increased with increasing SCr tertiles, being 1.5%, 5.5% (RR 2.51, CI 1.01-4.93)
      and 7.7% (RR 3.50, CI 1.41-5.88), respectively. The relationship between Crcl and
      CHD was inverse and increased with decreasing Crcl [2.7%, 3.3% (RR 1.42, CI 0.74
      2.26) and 6.7% (RR 2.78, CI 1.56-4.12) in the 3rd, 2nd and 1st tertiles,
      respectively]. CONCLUSIONS: SCr independently predicts CHD mortality in elderly
      men, but not in women. The increased CHD risk observed for SCr levels within the
      normal range is probably due to a sub-clinical impairment of renal function.

PMID- 16299690
TI  - Nodular glomerulosclerosis in a non-diabetic patient: case report and review of
      literature.
AB  - We report a unusual case of idiopathic nodular glomerulosclerosis mimicking
      changes that develop in diabetic nephropathy. A 66-year-old non-diabetic female
      developed nephrotic range proteinuria and the work up was unremarkable. Light and
      electron microscopy showed mesangial expansion with Kimmelsteil-Wilson nodules
      and diffuse glomerular basement membrane thickening without any electron dense
      deposits. Diabetes mellitus was excluded by repeated clinical and laboratory
      investigations. Forty two similar cases have been reported. Exact etiology for
      the development of non-diabetic glomerulosclerosis is unclear. But, hypertension,
      smoking, obesity, intermittent hyperglycemia predating the diagnosis of diabetes
      possibly explain the development of nodular glomerulosclerosis in these patients.
      Long-term follow-up to screen for the delayed onset of diabetes or its
      complications may be worthwhile.

PMID- 16299691
TI  - Co-existent crescentic glomerulonephritis and renal amyloidosis: a case report
      and literature review.
AB  - Co-existent crescentic glomerulonephritis and renal amyloidosis have only rarely
      been reported thus far. To our knowledge, only about eighteen convincing cases
      (with >50% crescents) have been described, mostly in the context of rheumatoid
      arthritis. In this report, we add a case from our institution and review the
      existing literature, including a proposed mechanism of crescent formation in this
      setting. Although the relationship between crescentic glomerulonephritis, renal
      amyloidosis, and rheumatoid arthritis needs further investigation, we suggest
      that one should consider the development of crescentic glomerulonephritis with
      amyloidosis in patients with long-standing rheumatoid arthritis and worsening
      renal function.

PMID- 16299692
TI  - Nephrotic syndrome and situs inversus viscerum: correlation or coincidence.
AB  - Asymmetric human internal organ organization has been a research topic for many
      years. Currently, although we know many mechanisms leading to the creation of
      specific internal organ organization, the problem requires further investigation.
      Transforming Growth Factor-beta superfamily (TGF-beta SF) molecules seem to play
      a major role in the process. They affect the cell by signaling through type I and
      II serine/threonine kinase receptors. Smad proteins seem vital in transmitting
      the signal between the receptor and the nucleus. We present the case of an 18
      year-old female patient, who was admitted to the hospital because of steroid
      sensitive nephrotic syndrome. Physical examination revealed that the patient also
      had a complete reversal of the intra-abdominal anatomy - situs inversus totalis.
      We suggest that disturbed TGF-beta and Smad signaling could be responsible for
      both nephrotic syndrome and situs inversus totalis.

PMID- 16299693
TI  - Autosomal dominant periodic fever with AA amyloidosis: tumor necrosis factor
      receptor-associated periodic syndrome (TRAPS) in a Turkish family.
AB  - We investigated the presence of tumor necrosis factor receptor-associated
      periodic syndrome (TRAPS) in a Turkish family with recurrent fever and systemic
      reactive (AA) amyloidosis. A missense mutation in exon 3 of the TNFRSF1A gene,
      resulting in an amino acid substitution Phe60Leu (F60L) was found in the proband
      and his father. These are the first confirmed TRAPS cases in the Turkish
      population. This family highlights the importance of onsidering all the causes of
      inherited fevers and performing thorough clinical and genetic investigations to
      secure a diagnosis, even in populations in which familial Mediterranean fever
      (FMF) is highly prevalent.

PMID- 16299694
TI  - Acute hyperkalemic paralysis in a uremic patient.
AB  - Hyperkalemia is a less-recognized life-threatening cause of paralysis. We
      describe a 38-year-old uremic man on regular hemodialysis (HD) without
      interruption who suffered from muscle weakness progressing to ascending symmetric
      paralysis, and inability to masticate. Physical examination revealed flaccid
      paralysis with areflexia of the four limbs. Computed tomography of the brain and
      cervical spine did not demonstrate any organic lesions. Laboratory investigations
      revealed serum K+ 8.1 mmol/L, urea nitrogen 32 mmol/L, creatinine 919 micromol/L.
      Of note, electrocardiography (ECG) did not show typical features of hyperkalemia.
      Emergent HD with low K+ dialysate (1.0 mmol/L) rapidly normalized serum K+ (4.7
      mmol/L) and reversed all neuromuscular symptoms within one hour. Upon reviewing
      his food and medication history, he admitted drinking 750 ml of raw coconut juice
      per day (K+ concentration 44.3 mmol/L) to quench his thirst for three consecutive
      days. Hyperkalemia should be born in mind in the differential diagnosis of acute
      paralysis despite no ECG changes. Hidden sources of K+ intake, such as coconut
      juice, should not be overlooked, especially in patients with impaired renal
      function.

PMID- 16299695
TI  - Quantitative liquid chromatography/tandem mass spectrometry determination of
      chloramphenicol residues in food using sub-2 microm particulate high-performance
      liquid chromatography columns for sensitivity and speed.
AB  - The use of chloramphenicol (CAP)--a highly effective broad-spectrum antibiotic
      used in animal husbandry--is banned in many countries. Therefore, a very low
      minimum required performance limit (MRPL) of 0.3 microg/kg CAP in meat for human
      consumption has been defined. Analytical methods capable of quantifying and
      confirming such low residue levels require sophisticated instrumentation.
      Preferably sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) or
      gas chromatography/mass spectrometry (GC/MS) methods have been used. This paper
      suggests the use of sub-2 microm particulate high-performance liquid
      chromatography (HPLC) columns to gain additional sensitivity and improve
      resolution as well as speed. Depending on the operating conditions, higher
      chromatographic resolution and speed can be obtained at the price of a
      significantly increased operating pressure, requiring dedicated LC equipment. A 3
      4-fold overall improvement of the signal-to-noise ratio for CAP was obtained
      compared to more classical 5 microm particulate HPLC columns. The proposed
      analytical methodology includes an enzymatic digestion, which liberates
      glucuronide-bound CAP from kidney tissue. The extracts obtained after an Extrelut
      clean-up are sufficiently pure to permit routine injection of biological samples
      into the sub-2 microm particulate HPLC column, without observing rapid
      deterioration of peak shape or column clogging problems. The time for one
      chromatographic run was 4.2 min. The described method was validated for two
      particularly difficult matrices (kidney and honey). Decision limits (CC alpha)
      were 0.007 microg/kg (honey) und 0.011 microg/kg (kidney), which are
      significantly below the current MRPL.

PMID- 16299696
TI  - Pharmacokinetic measurements of IDN 5390 using electrospray ionization tandem
      mass spectrometry: structure characterization and quantification in dog plasma.
AB  - In this report, electrospray ionization tandem mass spectrometry (ESI-MS/MS) for
      a pharmacokinetic study of IDN 5390, a novel C-seco taxane derivative, which is
      under preclinical evaluation, has been investigated. Our results showed that IDN
      5390 and other taxanes including paclitaxel and IDN 5109 could ionize well in not
      only positive-, but also in negative-ion mode. Under collision-induced
      dissociation (CID) conditions, these compounds could fragment into similar M-
      (molecular), T- (taxane ring) and S- (side chain) series ions. In positive-ion
      ESI, the formation of both T- and S-series ions involved the breaking of the C-13
      ester bond. In negative-ion ESI, however, while the formation mechanism of S
      series ions remained the same, the breaking of the C-1' carboxylic ester bond
      resulted in T-series ions. At optimum collision energy (CE) values, M-, T- and S
      series ions of IDN 5390 in both positive- and negative-ion ESI-MS/MS spectra had
      good intensity. This phenomenon makes both positive- and negative-ion ESI-MS/MS
      good methods for IDN 5390 metabolite structural characterization, i.e. to reveal
      the location of modification groups in IDN 5390 metabolites versus IDN 5390
      either on the side chain or the taxane ring. A liquid chromatography (LC)/ESI
      MS/MS method using the multiple-reaction monitoring (MRM) technique was
      thereafter developed to quantify IDN 5390 in dog plasma using paclitaxel as
      internal standard. The method was validated using a concentration range between 5
      and 1000 ng/mL and had a limit of detection of 1 ng/mL. The inter-day %CV
      (%coefficient of variation) of the calibration standards ranged between 4.36 and
      9.64%, the intra-day %CV of the calibration standards between 0.61 and 13.44%,
      and the mean % accuracy of the quality control samples at the low, middle and
      high end of the concentration curves were 12.5, 6.8 and 9.6%, respectively.

PMID- 16299697
TI  - Identification of the aromatase inhibitor letrozole in urine by gas
      chromatography/mass spectrometry.
AB  - Letrozole (1-(bis-(4-cyanophenyl)methyl)-1,2,4-triazole) is used therapeutically
      as a non-steroidal aromatase inhibitor (Femara) to treat hormone-sensitive breast
      cancer in postmenopausal women. For doping purposes it may be used to counteract
      the adverse effects of an extensive abuse of anabolic androgenic steroids
      (gynaecomastia) and to increase the testosterone concentration by stimulation of
      the testosterone biosynthesis. The use of aromatase inhibitors has been
      prohibited by IOC/WADA regulations for male and female athletes since September
      2001 and January 2005, respectively. Spot urine samples from women suffering from
      metastatic breast cancer and being treated with letrozole were collected and
      analysed to develop/optimise the detection system for metabolites of letrozole to
      allow the identification of athletes who do not comply with the internationally
      prohibited use of this cancer drug. The assay was based on gas
      chromatography/mass spectrometry (GC/MS) and the main metabolite of letrozole
      (bis-4-cyanophenylmethanol) was identified by comparison of its mass spectrum and
      retention time with that of a bis-4-cyanophenylmethanol reference. The full-scan
      spectrum, diagnostic ions and a validation of the method for the analysis of bis
      4-cyanophenylmethanol are presented.

PMID- 16299698
TI  - High sensitivity determination of valproic acid in mouse plasma using semi
      automated sample preparation and liquid chromatography with tandem mass
      spectrometric detection.
AB  - A high-throughput liquid chromatography/electrospray ionization tandem mass
      spectrometry (LC/ESI-MS/MS) assay using automated sample preparation has been
      developed for the determination of valproic acid (VPA) in mouse plasma. A liquid
      handling system was programmed to prepare calibration standard solutions in
      plasma, as well as quality controls and clinical samples. Plasma protein
      precipitation was performed on a 96-well plate, and the collected supernatant was
      directly injected into a reversed-phase LC/ESI-MS/MS system in the negative
      ionization mode. The calibration curve for VPA was linear over a dynamic range of
      0.15-100 microg/mL. The limit of detection was 75 ng/mL and the lower limit of
      quantitation was 150 ng/mL. Intra- and inter-day validation assays of the semi
      automated plasma analysis showed satisfactory accuracy and precision.

PMID- 16299699
TI  - Electrospray-assisted laser desorption/ionization mass spectrometry for direct
      ambient analysis of solids.
AB  - A new method of electrospray-assisted laser desorption/ionization (ELDI) mass
      spectrometry, which combines laser desorption with post-ionization by
      electrospray, was applied to rapid analysis of solid materials under ambient
      conditions. Analytes were desorbed from solid metallic and insulating substrata
      using a pulsed nitrogen laser. Post-ionization produced high-quality mass spectra
      characteristic of electrospray, including protein multiple charging. For the
      first time, mass spectra of intact proteins were obtained using laser desorption
      without adding a matrix. Bovine cytochrome c and an illicit drug containing
      methaqualone were chosen in this study to demonstrate the applicability of ELDI
      to the analysis of proteins and synthetic organic compounds.

PMID- 16299700
TI  - The global burden of selected occupational diseases and injury risks: Methodology
      and summary.
AB  - BACKGROUND: Around the globe, work has a heavy impact on health. To better advise
      policy makers, we assessed the global burden of disease and injury due to
      selected occupational hazards. This article presents an overview, and describes
      the methodology employed in the companion studies. METHODS: Using the World
      Health Organization (WHO) Comparative Risk Assessment methodology, we applied
      relative risk measures to the proportions of the population exposed to selected
      occupational hazards to estimate attributable fractions, deaths, and disability
      adjusted life years (DALYs). Numerous occupational risk factors had to be
      excluded due to inadequate global data. RESULTS: In 2000, the selected 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. These risks at work caused 850,000 deaths
      worldwide and resulted in the loss of about 24 million years of healthy life.
      Needlesticks accounted for about 40% of Hepatitis B and Hepatitis C infections
      and 4.4% of HIV infections in health care workers. CONCLUSIONS: Exposure to
      occupational hazards accounts for a significant proportion of the global burden
      of disease and injury, which could be substantially reduced through application
      of proven risk prevention strategies.

PMID- 16299702
TI  - Moving knowledge of global burden into preventive action.
AB  - BACKGROUND: Estimation of the global burden of disease and injury due to selected
      occupational factors is a topic of interest to policy makers, governments, and
      international bodies. The World Health Organization (WHO) has implemented a
      Comparative Risk Assessment (CRA) to estimate risk to exposed populations.
      METHODS: Estimates of the risk factor-burden relationships by age, sex, and WHO
      subregion were generated. Risk measurements (relative risks and mortality rates)
      for the health outcomes were determined primarily from studies published in peer
      review journals. The resulting burden was described as the attributable fraction
      of disease or injury, using both mortality and disability-adjusted life years
      (DALYs). RESULTS: The papers in this issue include discussions of worldwide
      mortality and morbidity from lung cancer, leukemia, and malignant mesothelioma
      arising from occupational exposures; mortality and morbidity from asthma, COPD,
      and pneumoconiosis; the global burden of low back pain; exposure to contaminated
      sharps injuries among health care workers; noise-induced hearing loss; and
      occupational injuries. Three papers focus on economic issues: estimation of net
      costs for prevention of occupational low back pain; cost effectiveness of
      occupational health interventions; and the cost effectiveness of interventions in
      the prevention of silicosis. CONCLUSIONS: The magnitude of the occupational
      health burden in the world is overwhelming, and the causes and mechanisms are
      multiple and complex. Commitment from all stakeholders is imperative to translate
      economic progress into sustainable human development and well-being.

PMID- 16299701
TI  - The global burden of non-malignant respiratory disease due to occupational
      airborne exposures.
AB  - BACKGROUND: Occupational non-malignant respiratory disease arises from exposure
      of workers to airborne agents, mostly particulate or dusts. We describe the
      worldwide mortality and morbidity from asthma, chronic obstructive pulmonary
      disease (COPD), and pneumoconioses arising from these occupational exposure and
      focus on cases reported in the year 2000. METHODS: The proportions of workers
      exposed to the agents, and their levels of exposure, were estimated using
      workforce data and the CAREX (CARcinogen EXposure) database. These were combined
      with relative risk measures (for asthma and COPD) or absolute risk measures (for
      the pneumoconioses) to develop estimates of deaths, disability-adjusted life
      years (DALYs) and attributable fraction (for asthma and COPD). RESULTS: There
      were an estimated 386,000 deaths (asthma: 38,000; COPD: 318,000; pneumoconioses:
      30,000) and nearly 6.6 million DALYS (asthma: 1,621,000; COPD: 3,733,000,
      pneumoconioses: 1,288,000) due to exposure to occupational airborne particulates.
      CONCLUSIONS: Occupational airborne particulates are an important cause of death
      and disability worldwide.

PMID- 16299703
TI  - The global burden of disease due to occupational carcinogens.
AB  - BACKGROUND: The worldwide mortality and morbidity from lung cancer, leukemia, and
      malignant mesothelioma arising from occupational exposures to carcinogens are
      described. Cases reported in the year 2000 that resulted from relevant past and
      current exposures are assessed. METHODS: The proportions of workers exposed to
      the carcinogens of interest, and their levels of exposure, were estimated using
      workforce data and the CAREX (CARcinogen EXposure) database. These were combined
      with relative risk measures (for lung cancer and leukemia) or absolute risk
      measures (for malignant mesothelioma) to develop estimates of deaths, disability
      adjusted life years (DALYs) and attributable fraction (for lung cancer and
      leukemia). RESULTS: There were an estimated 152,000 deaths (lung cancer: 102,000;
      leukemia: 7,000; and malignant mesothelioma: 43,000) and nearly 1.6 million DALYS
      (lung cancer: 969,000; leukemia: 101,000; and malignant mesothelioma: 564,000)
      due to exposure to occupational carcinogens. CONCLUSIONS: Occupational
      carcinogens are an important cause of death and disability worldwide.

PMID- 16299704
TI  - The global burden of occupational noise-induced hearing loss.
AB  - BACKGROUND: Excessive noise is a global occupational health hazard with
      considerable social and physiological impacts, including noise-induced hearing
      loss (NIHL). This paper describes the worldwide morbidity of occupational NIHL in
      the year 2000. METHODS: The proportion of the population exposed to occupational
      noise was estimated using noise exposure data from the US National Institute for
      Occupational Safety and Health (NIOSH), adjusted by data on the distribution of
      the work force by occupational category and economic sector, and economic
      activity rates in each WHO subregion. These values for the exposed population and
      risk measures for NIHL were used to develop estimates of the attributable
      fraction (AF) of adult-onset hearing loss resulting from occupational noise
      exposure. The AFs were applied to WHO estimates of total disability-adjusted life
      years (DALYs) from adult-onset hearing loss to estimate the DALYs due to
      occupational noise. RESULTS: Worldwide, 16% of the disabling hearing loss in
      adults (over 4 million DALYs) is attributed to occupational noise, ranging from
      7% to 21% in the various subregions. The effects of the exposure to occupational
      noise are larger for males than females in all subregions and higher in the
      developing regions. CONCLUSIONS: Occupational noise is a significant cause of
      adult-onset hearing loss. The majority of this NIHL burden can be minimized by
      the use of engineering controls to reduce the generation of noise at its source.

PMID- 16299705
TI  - Review of estimates of the global burden of injury and illness due to
      occupational exposures.
AB  - BACKGROUND: Over the last decade, there have been several attempts to estimate
      the global burden of ill health due to work activity. The most recent of these is
      the Comparative Risk Assessment (CRA) project of the World Health Organization.
      METHODS: Published estimates of global burden of injury and disease due to
      occupational factors were summarized, compared, and contrasted with the aim of
      putting the CRA estimates into context, identifying the most reliable and
      appropriate estimate for total burden due to occupational risks, and making
      recommendations regarding future work. RESULTS: The best estimate of global work
      related deaths of workers is approximately two million per year, with disease
      responsible for the vast majority of these, but even this is likely to be a
      considerable underestimate of the true number of deaths because of shortcomings
      in the available data. CONCLUSIONS: The CRA estimates of burden due to individual
      risk factors appear appropriate for the limited number of exposures and
      conditions included, but are a major underestimate of the overall number of work
      related deaths at a global level due to exclusion of risk factors because of data
      limitations. Improvements in global estimates are likely to come from the use of
      different methodologies and improvements in the availability and use of local
      data.

PMID- 16299706
TI  - The cost effectiveness of occupational health interventions: preventing
      occupational back pain.
AB  - BACKGROUND: Occupational back pain exacts a toll on society with concomitant
      economic losses; it is imperative to evaluate the cost-effectiveness of
      interventions to reduce the relevant ergonomic stressors at work. This study
      estimates and evaluates the average and incremental cost-effectiveness ratios
      (CERs) of specific interventions for the prevention of occupationally induced
      back pain for the World Health Organization (WHO) defined subregions of the
      world. METHODS: Four back-pain interventions were selected from the literature:
      training (T), engineering controls (EC), engineering controls and training
      (EC&T), and a comprehensive full ergonomics program (EP) for evaluation. A
      simulation model for a 100-year time horizon, developed by the WHO CHOICE
      initiative project was used to estimate the effectiveness of the interventions in
      healthy year equivalents. The intervention costs were adjusted for all WHO
      subregions. RESULTS: In all of the subregions, training was the most cost
      effective with CERs varying from 74 dollars per healthy life years gained in the
      subregion comprising of Egypt, Iraq, Morocco, Yemen (EMROD) to approximately 567
      dollars in the subregion covering Canada and the United States (AMROA). Training
      is considered to be very cost-effective and would be the first choice option
      where resources are scarce. However, the overall effectiveness of training is
      low. Although other interventions such as engineering controls and total
      ergonomic interventions are relatively more expensive, the addition to health
      outcome through these interventions is much higher. The difference in the CERs
      for training and other engineering controls and full ergonomic interventions is
      relatively small for most of the industrialized regions of the world. It is clear
      from the ranked CERs and incremental CERs over the different subregions that in
      most of the industrialized regions of the world additional resources, if they
      become available, should go straight to the full ergonomics program. CONCLUSIONS:
      The model results based on CERs show that worker training is a low cost, feasible
      first step toward reducing back pain/injury incidence. However, all of the
      average CERs for the different interventions, for each of the regions, fall well
      within their GDP per capita estimates [World Bank, 2001]. According to the WHO
      Commission on Macroeconomics and Health any intervention that costs less than
      three times GDP per capita for saving a healthy year equivalent should be
      considered worthwhile and good value for money [WHO, 2002]. Given this criterion,
      the engineering controls interventions as well as the full ergonomics program
      look very cost effective for all of the WHO subregions.

PMID- 16299707
TI  - Estimation of net-costs for prevention of occupational low back pain: three case
      studies from the US.
AB  - BACKGROUND: Occupational low back pain (OLBP) is widespread in industrialized
      societies. We present a model to estimate the net economic costs of investments
      in ergonomic interventions at the company level to reduce work-related low back
      pain. METHODS: Costs of interventions are defined by incorporating not only the
      costs of investment of equipment and labor, but also by taking into account the
      avoided costs of lost work time, medical care costs, and productivity
      improvements. In the net-cost model, all costs are annualized and are calculated
      at the level of an individual organization. Three case studies have been
      performed based on data from three companies in the manufacturing sector of the
      United States using the above approach. RESULTS: The net-cost estimates for the
      three case studies consistently show that ergonomic interventions applied
      appropriately can result in substantial cost savings for the companies.
      CONCLUSIONS: Although generalizing on the basis of three case studies is not
      ideal, our analyses show that it might be in the economic interest of management
      to play a more active role to prevent back pain. Gathering useful retrospective
      cost data, even on interventions deemed effective by corporate innovators, proved
      to be extremely difficult. We conclude that it is essential to incorporate a
      protocol for collecting cost and effectiveness data in the standard operating
      procedures of ergonomists and companies introducing such innovation. We intend to
      validate the net-cost model for the monitoring and reporting of such data through
      prospective studies in a variety of industrial settings and in countries at
      various stages of economic development.

PMID- 16299708
TI  - Estimating the global burden of low back pain attributable to combined
      occupational exposures.
AB  - BACKGROUND: There is little information about the global burden of non-traumatic
      low back pain (LBP) attributable to the effects of physical and psychosocial
      occupational stressors. METHODS: Based on a review of the epidemiological
      evidence, occupation-specific relative risks were used to compute attributable
      proportions by age, gender, and geographical sub-region for the economically
      active population aged 15 and older. The reference group was
      professional/administrative workers; other risk categories were Low, clerical and
      sales; Moderate, operators (production workers) and service; and High, farmers.
      RESULTS: Worldwide, 37% of LBP was attributed to occupation, with twofold
      variation across regions. The attributable proportion was higher for men than
      women, because of higher participation in the labor force and in occupations with
      heavy lifting or whole-body vibration. Work-related LBP was estimated to cause
      818,000 disability-adjusted life years lost annually. CONCLUSIONS: Occupational
      exposures to ergonomic stressors represent a substantial source of preventable
      back pain. Specific research on children is needed to quantify the global burden
      of disease due to child labor.

PMID- 16299709
TI  - The global burden due to occupational injury.
AB  - BACKGROUND: Occupational injuries are a public health problem, estimated to kill
      more than 300,000 workers worldwide every year and to cause many more cases of
      disability. We estimate the global burden of fatal and non-fatal unintentional
      occupational injuries for the year 2000. METHODS: The economically active
      population (EAP) of about 2.9 billion workers was used as a surrogate of the
      population at risk for occupational injuries. Occupational unintentional injury
      fatality rates for insured workers, by country, were used to estimate WHO
      regional rates. These were applied to regional EAP to estimate the number of
      deaths. In addition to mortality, the disability-adjusted life years (DALYs)
      lost, which measure both morbidity and mortality, were calculated for 14 WHO
      regions. RESULTS: Worldwide, hazardous conditions in the workplace were
      responsible for a minimum of 312,000 fatal unintentional occupational injuries.
      Together, fatal and non-fatal occupational injuries resulted in about 10.5
      million DALYs; that is, about 3.5 years of healthy life are lost per 1,000
      workers every year globally. Occupational risk factors are responsible for 8.8%
      of the global burden of mortality due to unintentional injuries and 8.1% of DALYs
      due to this outcome. CONCLUSIONS: Occupational injuries constitute a substantial
      global burden. However, our findings greatly underestimate the impact of
      occupational risk factors leading to injuries in the overall burden of disease.
      Our estimates could not include intentional injuries at work, or commuting
      injuries, due to lack of global data. Additional factors contributing to grave
      underestimation of occupational injuries include limited insurance coverage of
      workers and substantial under-reporting of fatal injuries in record-keeping
      systems globally. About 113,000 deaths were probably missed in our analyses due
      to under-reporting alone. It is clear that known prevention strategies need to be
      implemented widely to diminish the avoidable burden of injuries in the workplace.

PMID- 16299710
TI  - Estimation of the global burden of disease attributable to contaminated sharps
      injuries among health-care workers.
AB  - BACKGROUND: The global burden of hepatitis B (HBV), hepatitis C (HCV), and human
      immunodeficiency virus (HIV) infection due to percutaneous injuries among health
      care workers (HCWs) is estimated. METHODS: The incidence of infections
      attributable to percutaneous injuries in 14 geographical regions on the basis of
      the probability of injury, the prevalence of infection, the susceptibility of the
      worker, and the percutaneous transmission potential are modeled. The model also
      provides the attributable fractions of infection in HCWs. RESULTS: Overall,
      16,000 HCV, 66,000 HBV, and 1,000 HIV infections may have occurred in the year
      2000 worldwide among HCWs due to their occupational exposure to percutaneous
      injuries. The fraction of infections with HCV, HBV, and HIV in HCWs attributable
      to occupational exposure to percutaneous injuries fraction reaches 39%, 37%, and
      4.4% respectively. CONCLUSIONS: Occupational exposures to percutaneous injuries
      are substantial source of infections with bloodborne pathogens among health-care
      workers (HCWs). These infections are highly preventable and should be eliminated.

PMID- 16299711
TI  - The cost effectiveness of occupational health interventions: prevention of
      silicosis.
AB  - BACKGROUND: The failure to recognize occupational health as an economic
      phenomenon limits the effectiveness of interventions ostensibly designed to
      prevent disease and injury. Hence, consideration of economic efficiency is
      essential in the evaluations of interventions to reduce hazardous working
      conditions. In this paper, we present an analysis of the cost effectiveness of
      alternative means of preventing silicosis. METHODS: To evaluate the cost
      effectiveness of specific interventions for the prevention of occupationally
      induced silicosis, we have used the simulation models based on the generalized
      cost-effectiveness analysis (GCEA) developed by the WHO-CHOICE initiative for two
      representative subregions namely AMROA (Canada, United States of America), and
      WPROB1 (China, Korea, Mongolia). RESULTS: In both of the two subregions,
      engineering controls are the most cost effective with ratios varying from 105.89
      dollars per healthy year or disability adjusted life year saved in AMROA to
      approximately 109 dollars in WPROB1. In the two subregions, the incremental cost
      effectiveness ratio of engineering controls (EC) looks most attractive. Although
      dust masks (DM) look attractive in terms of cost, the total efficacy is extremely
      limited. CONCLUSIONS: To the extent that this analysis can be generalized across
      other subregions, it suggests that engineering control programs would be cost
      effective in both developed and developing countries for reducing silica exposure
      to save lives. Note that this analysis understates health benefits since only
      silicosis and not all silica-related diseases are considered.

PMID- 16299712
TI  - Intrinsic unstructuredness and abundance of PEST motifs in eukaryotic proteomes.
AB  - The study of unfolded protein regions has gained importance because of their
      prevalence and important roles in various cellular functions. These regions have
      characteristically high net charge and low hydrophobicity. The amino acid
      sequence determines the intrinsic unstructuredness of a region and, therefore,
      efforts are ongoing to delineate the sequence motifs, which might contribute to
      protein disorder. We find that PEST motifs are enriched in the characterized
      disordered regions as compared with globular ones. Analysis of representative PDB
      chains revealed very few structures containing PEST sequences and the majority of
      them lacked regular secondary structure. A proteome-wide study in completely
      sequenced eukaryotes with predicted unfolded and folded proteins shows that PEST
      proteins make up a large fraction of unfolded dataset as compared with the folded
      proteins. Our data also reveal the prevalence of PEST proteins in eukaryotic
      proteomes (approximately 25%). Functional classification of the PEST-containing
      proteins shows an over- and under-representation in proteins involved in
      regulation and metabolism, respectively. Furthermore, our analysis shows that
      predicted PEST regions do not exhibit any preference to be localized in the C
      terminals of proteins, as reported earlier.

PMID- 16299713
TI  - Reduction of vividness and associated craving in personalized food imagery.
AB  - This study aimed to extend recent experimental work on the efficacy of visuo
      spatial working memory-based techniques for reducing food cravings by adopting a
      more naturalistic methodology. Fifty undergraduate women formed images of their
      favorite foods while performing a visuo-spatial task across six successive
      trials. Vividness and craving intensity were rated for each food image.
      Concurrent visuo-spatial processing reduced the vividness of, and craving
      reactivity to, personally relevant food images. Forehead tracking, a novel self
      administered task, proved to be as effective in reducing vividness and craving
      ratings as the established visuo-spatial working memory laboratory tasks of eye
      movements, dynamic visual noise, and spatial tapping, and thus presents a simple,
      accessible technique potentially applicable in the home environment. All four
      tasks maintained their reducing effect over multiple trials. Individual
      differences in imaging ability and habitual food craving did not impact upon
      their effectiveness, indicating that visuo-spatial tasks can be successfully used
      to reduce food cravings across a range of people.

PMID- 16299714
TI  - Aberrant cellular immune responses in humans infected persistently with
      parvovirus B19.
AB  - A subset of parvovirus B19 (B19) infected patients retains the infection for
      years, as defined by detection of B19 DNA in bone marrow. Thus far, analysis of
      B19-specific humoral immune responses and viral genome variations has not
      revealed a mechanism for the absent viral clearance. In this study, ex-vivo
      cellular immune responses were assessed by enzyme linked immunospot assay mounted
      against the majority of the translated viral genome. Compared to seropositive
      healthy individuals, individuals with B19 persistence (2-8 years) showed larger
      number of responses to the structural proteins (P = 0.0022), whereas responses to
      the non-structural protein were of lower magnitude (P = 0.012). These
      observations provide the first findings of immunological discrepancies between
      individuals with B19 persistence and healthy individuals, findings that may
      reflect both failed immunity and antigenic exhaustion.

PMID- 16299715
TI  - Predictive factors of virological non-response to interferon-ribavirin
      combination therapy for patients infected with hepatitis C virus of genotype 1b
      and high viral load.
AB  - Patients with high viral load (> or =1.0 x 10(5) IU/ml) of hepatitis C virus
      (HCV) genotype 1b do not achieve high sustained virological response rates to
      interferon (IFN)/ribavirin combination therapy. Previous studies suggested that
      pretreatment amino acid (aa) substitution patterns in the HCV core region could
      affect virological non-response especially in patients who could not achieve HCV
      RNA negativity during treatment. The present study evaluated 167 consecutive
      Japanese adults with high HCV genotype 1b viral load who received combination
      therapy for > or =24 weeks. A case-control study matched for age, sex, genotype,
      and viral load was conducted to investigate the predictive factors for
      virological non-response, especially absolute virological non-response (patients
      who could not achieve >2 log decline of HCV RNA from baseline during the initial
      24 weeks of therapy). Virological non-response was identified in 26.3% of
      patients, and 45.5% of these were absolute virological non-responders.
      Multivariate analysis identified ribavirin dose <11.0 mg/kg, moderate-to-severe
      hepatocyte steatosis, and substitutions of aa 70 and/or 91 in the core region as
      significant independent factors associated with virological non-response. The
      majority of absolute virological non-responders had such substitutions in the
      core region (95.0%), as well as substitution of glutamine at aa 70 and/or
      methionine at aa 91 (90.0%). In the present work, such substitutions
      significantly affected the viral kinetics in virological non-responders. The
      results suggest that viral, host, and treatment-related factors determine the
      response to IFN/ribavirin combination therapy in patients with high HCV genotype
      1b viral load, and that amino acid substitution patterns in the core region is
      potentially useful pretreatment predictor of virological non-response.

PMID- 16299716
TI  - Tracing the history of hepatitis B virus genotype D in western Japan.
AB  - The major hepatitis B virus (HBV) genotypes in Japan are B and C. HBV genotype D
      (HBV/D), however, is widespread in a small area of Western Japan, where the
      Gianotti-Crosti syndrome caused by HBV subtype ayw, which is suspected to be
      HBV/D, was endemic in the 1970s. The aim of the study was to elucidate its
      origin, time of transmission, and spread in this area. Genotyping of HBV-DNA was
      done in 363 patients with HBV infection. The year of birth was checked in
      patients with HBV/D. The full genome sequences of 20 HBV/D strains, 2 of which
      were obtained from a single carrier with a 19-year-interval, were analyzed. An
      evolutionary rate, the date of the most recent common ancestor, and the effective
      number of HBV/D infections were calculated. Fifty-two of 363 patients were
      infected with HBV/D, and 39 were born in 1970s. In a phylogenetic tree, the 20
      HBV/D strains produced a definite cluster, and the evolutionary rate was
      calculated to be 5.4 x 10(-5) nucleotide substitutions/site/year. The root of the
      tree was estimated to be in approximately 1,900 and began to spread from the
      1940s, leading to a rapid increase of infected patients in the 1970s. From these
      results, it is suspected that HBV/D was likely transmitted to the area
      investigated approximately 100 years ago and then spread widely in the 1970s.
      From the history of the area and the genetic analysis, HBV/D in this area was
      speculated to be of Russian origin.

PMID- 16299717
TI  - Rapid and simple detection of IFN-neutralizing antibodies in chronic hepatitis C
      non-responsive to IFN-alpha.
AB  - Different mechanisms have been proposed for the failure of interferon (IFN)
      therapy in patients with chronic hepatitis C and multiple sclerosis, for example,
      the presence of IFN-neutralizing antibodies. In this study, a novel assay system
      based on the IFN-inducible Mx-promoter was used to detect IFN-neutralizing
      antibodies in sera of patients with chronic hepatitis C. To monitor IFN
      bioactivity in IFN-treated patients, a real-time RT-PCR for MxA gene expression
      in PBMCs was established. Using these two methods, patients with chronic
      hepatitis C virus (HCV) infection receiving IFN therapy and patients with
      treatment induced HCV clearance were monitored. Importantly, neutralizing anti
      IFN antibodies were detected in the sera of 3 of 38 chronically HCV-infected
      patients who failed to respond to therapy but none in sera of patients who
      cleared HCV after IFN therapy. Interestingly, the presence of these antibodies
      correlated with the lack of MxA induction in PBMCs after initiation of IFN-alpha
      therapy. Retrospective analysis of one patient's sera revealed that the anti-IFN
      alpha antibodies had already developed after the first of four unsuccessful IFN
      therapies, suggesting that neutralizing antibodies may have contributed to the
      failure of previous IFN treatments. In summary, a novel screening assay was
      established that may be helpful for testing IFN non-responders for the presence
      of clinically relevant anti-IFN-alpha antibodies and for selecting alternative
      IFN preparations not neutralized by these antibodies.

PMID- 16299718
TI  - Latent infection of human herpesvirus 7 in CD4(+) T lymphocytes.
AB  - To determine the cell populations in peripheral blood that are infected latently
      with human herpesvirus 7 (HHV-7), the real-time polymerase chain reaction (PCR)
      was used to determine the quantities of viral DNA in adherent and non-adherent
      cells from 71 healthy volunteers. Real-time PCR, which detected the U31 gene of
      HHV-7, was developed to measure viral load. The majority of non-adherent cells
      (14/16; 87.5%) contained HHV-7 DNA, while most of the adherent cells did not
      (1/16; 6.3%). HHV-7 viral load in non-adherent cells was significantly higher
      than that in adherent cells (P < 0.0001). Then, HHV-7 DNA load was compared
      between the CD4-positive and -negative cell fractions derived from the non
      adherent cells of 26 healthy adults. As in the previous experiment, only 2 (7.7%)
      of the 26 adherent cell specimens contained small amounts of HHV-7 DNA (27.7
      copies/1 x 10(6) cells and 208.7 copies/1 x 10(6) cells). In contrast, 88.5% of
      CD4(+) T cell samples (23/26 specimens) were positive for HHV-7 DNA, ranging from
      0.4 to 3,542.8 copies/1 x 10(6) cells. Viral DNA was detected in only 3 (11.5%)
      of the 26 CD4(-) T cell specimens, with 8.4, 63.5, and 74.1 copies/1 x 10(6)
      cells. HHV-7-positive DNA loads were significantly higher in the CD4(+) T cells
      than those observed in the CD4(-) T cells (P = 0.0005). The relationship between
      HHV-7 viral loads in non-adherent cells and those in saliva was investigated.
      Comparison of HHV-7 DNA load between blood CD4(+) T cells and saliva revealed
      that the HHV-7 DNA load in saliva correlated with that present in CD4(+) T cells
      (r = 0.415; P = 0.0174).

PMID- 16299719
TI  - Dual infection due to simian G3--human reassortant and human G9 strains of
      rotavirus in a child and subsequent spread of serotype G9, leading to diarrhea
      among grandparents.
AB  - Cultivation of rotavirus from day 1 and 3 fecal specimens of a child yielded
      simian SA11-human reassortant, G3P[8] and AU32 like G9P[8] rotavirus strains,
      respectively. Diarrhea developed in the grandfather by sheer hospital visits, and
      in the grandmother, after wiping the vomit of the grandfather. AU32 like G9
      strains were isolated from the grandparents also. Rotavirus specific IgM
      developed in all the three patients. A fourfold rise in G9 neutralizing
      antibodies was observed in the child and grandmother. The child's mother had
      asymptomatic rotavirus infection. The study highlights the potential of G9
      serotype to spread from children to adults.

PMID- 16299720
TI  - Seroepidemiology of hepatitis A, B, C, and E viruses infection among preschool
      children in Taiwan.
AB  - Taiwan was a hyperendemic area for hepatitis A and B viruses (HAV and HBV)
      infection before late 1980s. To study the seroprevalence of hepatitis A, B, C,
      and E viruses (HCV and HEV) infection among preschool children in Taiwan, a
      community-based survey was carried out in 54 kindergartens in 10 urban areas, 10
      rural areas, and 2 aboriginal areas randomly selected through stratified
      sampling. Serum specimens of 2,538 preschool children were screened for the
      hepatitis A, C, and E antibodies by a commercially available enzyme immunoassay
      and for HBV markers by radioimmunoassay methods. The multivariate-adjusted odd
      ratios (OR) with their 95% confidence intervals (CI) were estimated through the
      multiple logistic regression analysis. Females had a statistically significantly
      higher HAV seroprevalence than males. The seroprevalence of HCV infection
      increased significantly with age. The larger the sibship size, the higher the
      seroprevalence of HBV infection. Aboriginal children had a significantly higher
      seroprevalence of HBV and HEV infection and lower seroprevalence of HCV infection
      than non-aboriginal children. A significantly higher seroprevalence of HBV
      infection was found in rural children than urban children. There was no
      significant association between serostatus of HAV and HEV infection and between
      serostatus of HBV and HCV infection among preschool children in Taiwan. The poor
      environmental and hygienic conditions in the aboriginal areas might play a role
      in infection with HBV and HEV.

PMID- 16299721
TI  - Virological outcomes in patients infected chronically with hepatitis B virus
      genotype A in comparison with genotypes B and C.
AB  - In a single hospital in Tokyo, the 87 patients infected persistently with
      hepatitis B virus (HBV) genotype A, the 413 with B, and the 3,389 with C were
      compared for virological outcome. Hepatitis B surface antigen (HBsAg) was cleared
      from the serum in 12% (3/26), 2% (2/112), and 3% (23/826) of patients with
      genotypes A, B, and C, respectively, at 5 years of follow-up (P = 0.0395).
      Hepatitis B e antigen (HBeAg) was cleared from serum more frequently in patients
      with genotype B than those with A or C (78% [32/41] vs. 58% [11/19] or 45%
      [251/562], P = 0.00001) at 5 years. Of the 45 individuals infected with genotype
      A and followed for 3 years or longer, HBeAg was more frequent (16% [3/19] vs. 73%
      [19/26], P = 0.0002) and levels of HBV DNA higher (median <2.6 [range: <2.6-5.6]
      vs. >7.6 [<2.6->7.6] log copies/ml, P = 0.001) in the 26 patients with biopsy
      proven chronic hepatitis than the 19 asymptomatic carriers. Among the 26
      hepatitis patients infected with HBV genotype A, decreases in HBV DNA were less
      frequent (20% [1/5] vs. 93% [13/14] or 86% [6/7], P = 0.0095) and increases in
      serum levels of hyaluronic acid > or =10 ng/ml commoner (80% [4/5] vs. 14% [2/14]
      or 14% [1/7], P = 0.017) in the patients who kept HBeAg than in those who
      seroconverted or who remained HBeAg-negative. In conclusion, patients
      persistently infected with HBV genotype A fare better than those with genotype B
      or C. However, high levels of HBV DNA continue in those in whom HBeAg persists
      along with fibrosis in the liver.

PMID- 16299722
TI  - Acute hemorrhagic conjunctivitis epidemic caused by coxsackievirus A24 variants
      in Korea during 2002-2003.
AB  - A variant of coxsackievirus A24 (CA24v) is one of the agents causing acute
      hemorrhagic conjunctivitis. There was an epidemic of acute hemorrhagic
      conjunctivitis caused by CA24v in Korea from 2002 to 2003. Seventy-one strains of
      CA24v were isolated from 159 conjunctival specimens (45%). Most of the patients
      were school children under the age of 20. The epidemic began in the first week of
      August in 2002, and spread extensively, with a peak in the third week of
      September. CA24v strains were also isolated from conjunctival specimens in 2003.
      Reverse transcription polymerase chain reaction (RT-PCR) was performed and
      sequencing of the 340 bp fragment of the VP1 region of the viruses. Sequencing
      data were multiple-aligned using CLUSTAL W (version 1.81). Phylogenetic trees
      were plotted using TreeView (version 1.6.6). Homologies ranged from 97.7%-100%,
      depending on geographical regions: from 99.4%-100% in 2002 and 98.4%-100% in
      2003. A phylogenetic tree based on the nucleotide sequence homologies formed
      clusters depending on years rather than on geographical regions. Identities (98%
      100%) were found among the Korean CA24v strains, and there was 85%-90% homology
      between these and the prototype strain.

PMID- 16299723
TI  - Establishment of functional B cell memory against parvovirus B19 capsid proteins
      may be associated with resolution of persistent infection.
AB  - Parvovirus B19 (B19) infection can occur during acute lymphoblastic leukemia and
      persistent viral infection can occur despite intravenous immunoglobulin
      administration. Here, evidence is presented that resolution of persistent B19
      infection in an acute lymphoblastic leukemia patient may be associated with the
      simultaneous strengthening of antigen-specific B cell memory against the B19
      capsid protein VP2 and diminution in the memory response against the B19 non
      structural protein 1 (NS1). Determination of antigen-specific B cell memory
      status may enhance the serological and molecular analyses of persistent B19
      infection.

PMID- 16299724
TI  - Antibody responses against SARS coronavirus are correlated with disease outcome
      of infected individuals.
AB  - Most of the SARS-CoV-infected patients spontaneously recovered without clinical
      intervention while a small percentage succumbed to the disease. Here, we
      characterized temporal changes in N protein-specific and S glycoprotein-specific
      neutralizing antibody (Nab) responses in infected patients who have either
      recovered from or succumbed to SARS-CoV infection. Recovered patients were found
      to have higher and sustainable levels of both N protein-specific and S
      glycoprotein-specific Nab responses, suggesting that antibody responses likely
      play an important role in determining the ultimate disease outcome of SARS-CoV
      infected patients.

PMID- 16299725
TI  - Frequency of hepatitis B virus 'a' determinant variants in unselected Spanish
      chronic carriers.
AB  - The prevalence in the population of hepatitis B virus (HBV) surface antigen
      (HBsAg) variants that may impair diagnosis, or allow the virus to escape vaccine
      induced immunity or passive immunoglobulin therapy is unknown. A genome fragment
      encoding HBsAg amino acids 112-212 was amplified and sequenced from the sera of
      272 unselected DNA-positive, HBV-chronic carriers from Spain. The genotype and
      the HBsAg subtype were predicted from the sequences. Analysis of amino-acid
      positions 112-157 revealed single or multiple substitutions in 39% of the
      carriers studied. Mutations were not detected for residues 121, 135, 137, 139,
      140, 141, 142, 146, 147, 148, 149, 151, 152, 153, 155, 156, and 157.
      Substitutions reported previously to be in association with failures of
      diagnostic tests or with vaccine or immunoglobulin therapy escape were found in
      12.5%, 6.6%, and 9.2% of carriers, respectively. Met133Thr (2.2%); Gln129His,
      Met133Ile, Phe/Tyr134Asn (1.8%); Phe/Tyr134Leu, Gly145Ala (1.5%), and Pro120Thr
      (1.1%) were the most frequent. Other substitutions, including Gly145Arg (0.4%),
      were found at a frequency of less than 1%. Samples containing HBV mutants were
      tested with three commercial assays for HBsAg screening. Almost all the mutants
      reacted to the upper cut-off values of the assays, but six samples with weak
      reactivity with one or more of the methods were also found. Thus, HBV mutants
      with a potential impact on clinical and public health issues are moderately
      frequent among chronic carriers from Spain, although their influence on the
      performance of diagnostic tests seems to be slight.

PMID- 16299726
TI  - Quantitative measurement of hepatitis B virus DNA in different areas of hepatic
      lobules in patients with chronic hepatitis B.
AB  - Liver histology in chronic hepatitis B is marked by inflammatory infiltration
      involving the peripheral zones. The cause of such cellular infiltration remains
      unknown. The aim of the present study was to investigate the amounts of
      intrahepatic hepatitis B virus (HBV) DNA separately in the peripheral and central
      zones, using laser capture microdissection coupled with real-time quantitative
      polymerase chain reaction. Fourteen patients with chronic hepatitis B were
      included in the study. Liver biopsy samples were taken and hepatocytes were
      microdissected separately from peripheral and central zones. DNA was extracted
      from hepatocytes in each zone and evaluated the amounts of HBV-DNA.
      Immunohistochemical study for hepatitis B core antigen (HBcAg) was also
      performed. The amounts of total intrahepatic HBV-DNA in patients positive for
      hepatitis Be antigen (HBeAg) were greater than those in HBeAg-negative patients.
      There was no difference in HBV-DNA between the peripheral and central zones.
      Immunohistochemistry also showed that HBcAg-positive cells were distributed
      homogeneously in the hepatic lobules. In patients with peripherally predominant
      HBV-DNA, the serum alanine aminotransferase (ALT) level was lower than in
      patients with centrally predominant HBV-DNA. HBV-DNA was distributed
      homogeneously in the hepatic lobules. In patients with lower amounts of HBV-DNA
      in the peripheral zone, the serum ALT level tended to be higher than in other
      patients.

PMID- 16299727
TI  - Genotype, phylogenetic analysis, and transmission pattern of occult hepatitis B
      virus (HBV) infection in families of asymptomatic HBsAg carriers.
AB  - Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in
      the serum in absence of hepatitis B surface antigen (HBsAg). Studies were
      conducted to screen for occult HBV infection among family members of HBV
      carriers, incidentally detected positive for HBV infection with a view to assess
      the pattern of virus transmission among them. Nested PCR assay, employing
      independent sets of primers to surface and core genes, was used for detection of
      HBV DNA in serum samples from 28 index cases with asymptomatic HBV infection, and
      in serum samples from 72 HBsAg negative/anti-HBc positive family members. HBV DNA
      was detected in 15 HBsAg negative family members of 10 HBsAg positive index
      patients and was studied in detail. Direct sequencing of S gene region of 25
      isolates (10 index cases and 15 contacts) and phylogenetic analysis with data
      base sequences revealed that genotypes A, C, and D and subtype adw2, adr, and
      ayw3 were present among them. Evidence of transmission from outside family
      sources was found in addition to intrafamilial transmission among individuals
      with occult infection. Mutations in the major hydrophilic loop (MHL) of the S
      gene region were also detected, including the 'vaccine escape' mutation G145R in
      three cases. Although majority of the occult infection was associated with low
      viral load, 3/15 (20%) cases were with higher viral load and potential
      infectivity. These cases are especially notable in diagnostic, blood banking, and
      transplantation services.

PMID- 16299728
TI  - Enterovirus meningitis in Brazil, 1998-2003.
AB  - Acute viral infections of the central nervous system (CNS) such as acute flaccid
      paralysis, meningitis, and encephalitis, are responsible for a high morbidity,
      particularly in children. Non-Polio enteroviruses (NPEV) are known to be
      responsible for over 80% of viral meningitis in which the etiologic agent is
      identified. In the present study, we show the frequency of enterovirus meningitis
      in Brazil from December 1998 to December 2003. Enterovirus were isolated from 162
      (15.8%), of a total of 1,022 cerebrospinal fluid (CSF) specimens analyzed.
      Echovirus 30 was identified in 139 of these isolates (139/162-85.2%). Other
      identified enteroviruses were: Coxsackievirus B5 (3.7%), Echovirus 13 (3.7%),
      Echovirus 18 (3%), Echovirus 6 (1.2%), Echovirus 25 (1.2%), Echovirus 1 (0.6%),
      and Echovirus 4 (0.6%). Patients's age ranged from 28 days to 68 years old. The
      most frequent symptoms were fever (77%), headache (69.5%), vomiting (71.3%), neck
      stiffness (41.3%), convulsion (7.1%), and diarrhea (3.7%). Although, the majority
      of the patients recovered without any complication or permanent squeal, five
      deaths occurred. Throughout the surveillance period, five viral meningitis
      outbreaks were confirmed: four in the Southern Brazil and one in the Northeast
      Brazil. Echovirus 30 was responsible for four out of the five outbreaks while
      Echovirus 13 caused the fifth one. Besides the outbreaks, 734 sporadic cases were
      also identified during the study period and 59 of these were positive for virus
      isolation (8%). Echovirus 30 accounted for 70% of the isolates. Our results
      showed that Echovirus 30 was the most prevalent etiological agent of viral
      meningitis in Brazil, causing both outbreaks and sporadic cases.

PMID- 16299729
TI  - A previously unrecognized sixth genotype of GB virus C revealed by analysis of 5'
      untranslated region sequences.
AB  - GB virus C (GBV-C) is a positive-strand RNA virus that infects a large proportion
      of the world's human population. It has been classified tentatively as a member
      of the Flaviviridae family and has been shown to exist as a group of five closely
      related genotypes. Recently, we reported the first full-length genome sequence of
      a genotype 5 isolate from South Africa. As part of the analysis of that sequence,
      a phylogenetic tree was elucidated from the 5'-untranslated region (UTR) that
      showed excellent congruence to the tree produced by analysis of complete open
      reading frame sequences. When 5'-UTR analysis was broadened subsequently to
      include additional isolates from around the globe, a heretofore unrecognized GBV
      C genotype was discovered in Indonesia. When first reported in 2000, these
      isolates were described as constituting a novel fifth genotype. However,
      comparison to isolates from the then-known fourth and fifth genotypes (from
      Myanmar/Vietnam and South Africa, respectively) was not performed. A dataset of
      121 GBV-C 5'-UTR sequences was complied and included representatives of the
      fourth and fifth genotypes as well as the "novel" Indonesian sequences and
      demonstrated, with strong support via bootstrap analysis, the existence of a
      sixth GBV-C genotype among infected individuals in Indonesia. The discovery of
      this sixth genotype emphasizes the diverse nature of GBV-C isolates and may have
      important implications for the interpretation of studies involving GBV-C/HIV co
      infected individuals.

PMID- 16299730
TI  - Detection of specific human papillomavirus types in paraffin-embedded sections of
      cervical carcinomas.
AB  - Human papillomaviruses (HPV) are the causative agents of most cervical
      carcinomas. A complete understanding of the HPV types that cause cervical
      carcinoma is needed as vaccines are designed. Fresh tissues are not always
      available for such studies. We therefore sought to determine the feasibility of
      HPV studies using formalin-fixed, paraffin-embedded sections of 56 cervical
      carcinomas, correlating typing information with the pathology and physical state
      of the HPV sequences within cells. Sections from each specimen were used to
      extract and purify DNA. Specific HPV types were identified using a PCR/reverse
      blot strip assay. Tyramide signal-amplified, fluorescent DNA in situ
      hybridization (FISH) was used to localize HPV within cells. Human beta-globin
      sequences were amplified in DNA from all specimens. HPV sequences from oncogenic
      types were identified in 52 of 56 (92.9%) by PCR/reverse blot strip assay, and in
      one additional case using an HPV 16 multiplex PCR assay. HPV 16 was the most
      commonly detected type, present in most cases as a solitary isolate. Thirty- five
      of 42 HPV 16 or HPV 18 PCR-positive specimens were also positive in the FISH
      assay, in most cases in a pattern consistent with viral integration. We conclude
      that HPV typing from formalin-fixed, paraffin-embedded sections of cervical
      carcinomas is possible, with a sensitivity that is similar to that found in
      studies using fresh tissue.

PMID- 16299731
TI  - Impact of unreported HIV-1 reverse transcriptase mutations on phenotypic
      resistance to nucleoside and non-nucleoside inhibitors.
AB  - An extended spectrum of HIV-1 reverse-transcriptase (RT) mutations in HAART
      treated patients has been recently described. To verify the possible association
      of previously unreported RT mutations with a decrease of phenotypic
      susceptibility to nucleoside (NRTIs) and non-nucleoside (NNRTIs) RT inhibitors,
      the RT sequence of 328 HIV-1-positive patients (102 naive and 226 treated with
      HAART participating in either the PhenGen or Genpherex study) was analyzed. All
      treated patients were tested at the time of therapeutic failure with both
      phenotypic (Antivirogram, Virco) and genotypic analyses (VircoGen); the frequency
      of RT substitutions (positions 1-240) with respect to consensus B was compared to
      that of naive patients using a Chi-square test. Amino acid changes at 13
      positions not included in the IAS list of resistance-associated mutations were
      detected more frequently in treated than in naive subjects. The mutations
      involving 10 of these positions were associated with a reduced susceptibility to
      antiretroviral drugs; K20R, T39A, K43EQN, E203KD, H208Y, and D218E were
      correlated with NRTI resistance while mutations K101EQP, H221Y, K223EQ, L228HR
      were associated to NNRTI resistance. A correlation was found between K20R and
      lamivudine resistance (P = 0.006) while T39A (P = 0.005), K43EQN (<0.001), E203KD
      (P = 0.010), and H208Y (P = < 0.001) seemed to be associated with a previous use
      of zidovudine and stavudine and with the development of thymidine analog
      resistance. For H208Y, an association with use/resistance to abacavir (P = 0.004)
      was also noted. D218E showed a weak association to didanosine resistance (P =
      0.013). The data confirm that previously unreported mutations are associated with
      antiretroviral drug experience and, more importantly, with a reduced
      susceptibility to NRTIs and NNRTIs.

PMID- 16299733
TI  - Patients with and without loss of hepatitis B virus DNA after hepatitis B e
      antigen seroconversion have different virological characteristics.
AB  - The characteristic differences between patients with and without loss of
      hepatitis B virus (HBV) DNA after achieving hepatitis B e antigen seroconversion
      were analyzed by comparing changes in HBV DNA and HBV core-related antigen levels
      during a period from 3 years before to 3 years after the seroconversion. Of the
      24 seroconverters, 6 (inactive replication group) showed continuous loss of HBV
      DNA in serum after the seroconversion and the remaining 18 did not lose HBV DNA
      (active replication group). The HBV DNA level was similar between the two groups,
      while the HBV core-related antigen level was significantly lower in the active
      replication group than in the inactive replication group before the
      seroconversion. The levels of both HBV DNA and HBV core-related antigen decreased
      remarkably around the time of seroconversion in the inactive replication group,
      while these levels did not change or decreased slightly in the active replication
      group. After the seroconversion, the HBV DNA level was significantly higher in
      the active replication group than in the inactive replication group, while the
      HBV core-related antigen level was similarly low between the two groups. Because
      the serum level of HBV core-related antigen mainly reflects that of HBe antigen,
      the low level of HBV core-related antigen seen after seroconversion in both
      groups might have contributed to the occurrence of seroconversion. The precore
      and core promoter mutations which cause diminished excretion of hepatitis B e
      antigen were significantly more frequent in the active replication group than in
      the inactive replication group. It was therefore considered that the
      seroconversion was caused mainly by a decrease in viral replication in the
      inactive replication group, and mainly by a decrease in HBe antigen production in
      the active replication group.

PMID- 16299734
TI  - Minimal structural requirements for root effect: crystal structure of the
      cathodic hemoglobin isolated from the antarctic fish Trematomus newnesi.
AB  - The cathodic hemoglobin component of the Antarctic fish Trematomus newnesi
      (HbCTn) is a Root-effect protein. The interpretation of its functional properties
      in relation to its sequence is puzzling. Indeed, HbCTn sequence is characterized
      by an extremely low histidyl content, and in particular by the lack of His146beta
      and His69beta, which are believed to be important in Bohr and Root effects,
      respectively. Furthermore, previous analyses suggested that the local environment
      of Asp95alpha, Asp99beta, and Asp101beta should not be appropriate for the
      formation of Asp-Asp interactions, which are important for the Root effect. Here,
      we report the high-resolution crystal structure of the deoxy form of HbCTn. Our
      data provide a structural interpretation for the very low oxygen affinity of the
      protein and insights into the structural determinants of the Root effect protein.
      The structure demonstrates that the presence of Ile41alpha and Ser97alpha at the
      alpha1beta2 interface does not prevent the formation of the inter-Asp
      interactions in HbCTn, as previous studies had suggested. The present data
      indicate that the hydrogen bond formed between Asp95alpha and Asp101beta, which
      is stabilized by Asp99beta, is per se sufficient to generate the Root effect, and
      it is the minimal structural requirement needed for the design of Root-effect
      Hbs.

PMID- 16299735
TI  - Nitric oxide and metastatic cell behaviour.
AB  - Nitric oxide (NO) is a pleiotropic signalling molecule that subserves a wide
      variety of basic cellular functions and also manifests itself
      pathophysiologically. As regards cancer and its progression, however, the
      reported role of NO appears surprisingly inconsistent. In this review, we focus
      on metastasis, the process of cancer cell spread and secondary tumour formation.
      In a 'reductionist' approach, we consider the metastatic cascade to be made up of
      a series of basic cellular behaviours (such as proliferation, apoptosis,
      adhesion, secretion migration, invasion and angiogenesis). We evaluate how NO
      controls such behaviours, in comparison with normal cells. The available
      information suggests strongly that NO signalling would be expected to regulate
      these behaviours both positively and negatively and this probably leads to the
      observed apparent variability in the NO status of cancer cells and tissues. Thus,
      the role of NO in cancer is more complex than previously thought. A number of
      suggestions are made, including consideration of novel mechanisms, such as ion
      channels, in order to achieve a more consistent and integrated understanding of
      NO signalling in cancer and to realise its clinical potential.

PMID- 16299736
TI  - Lymphangioma of the posterior mediastinum in an adult: diagnosis via
      cytopathologist-assisted fine-needle aspiration biopsy with cell block.
AB  - Lymphangiomas are uncommon in the posterior mediastinum. We report a case of a
      lymphangioma in this location that was diagnosed by computed tomographic-guided
      fine-needle aspiration biopsy. The cell block of the lesion closely simulated a
      normal structure immediately adjacent to the target and could have been
      misdiagnosed as "normal tissue." On-site evaluation of the aspirate by a
      cytopathologist promoted pathologist-radiologist communication that helped
      prevent the potential error and facilitated making the correct diagnosis in the
      case.

PMID- 16299737
TI  - Thyroglossal duct cyst: a cytopathologic study of 26 cases.
AB  - Thyroglossal duct cyst (TDC), or embryologic remnants of thyroid gland, is a
      common congenital anomaly. TDC may cause a midline neck mass, which occasionally
      may become infected, and rarely gives rise to carcinoma. As a number of other
      nonneoplastic and neoplastic lesions can cause cystic masses in the neck, we
      explored the role of fine-needle aspiration (FNA) in making a preoperative
      diagnosis of TDC for a more accurate and timely clinical intervention. Twenty-six
      cases of TDC were identified from the cytopathology files of The Johns Hopkins
      Hospital in a 15-yr period (1990-2004). Material was obtained by FNA with or
      without radiologic (ultrasound) guidance. Smears were air-dried and stained with
      Diff-Quik, or wet-fixed and stained with Papanicolaou stain. Cytomorphologic
      characteristics were serially analyzed. Follow-up (tissue resection [n = 9] and
      clinical charts [n = 17]) was reviewed in all cases. Patients ranged in age from
      8 to 83 yr (mean age, 55) with M:F ratio of 1.4:1. The size of the cyst ranged
      from 1.2 to 5 cm (mean 2.5 cm), as evaluated on radiological scans. The most
      common clinical presentation was a non-tender, mobile neck mass, which was
      painful on swallowing. Follow-up confirmed TDC in 18/26 cases (69%), whereas 8/26
      cases resulted in various other benign lesions. During the same time period,
      11/18 (61%) cases of surgically resected TDC were missed on prior FNA. Therefore,
      FNA showed a diagnostic sensitivity of 62% and a positive predictive value (PPV)
      of 69% for the diagnosis of TDC. The cytomorphologic features of TDC included the
      following: colloid (thick and fragmented, thin and watery, or mucinous),
      macrophages, lymphocytes, or predominantly neutrophils. The epithelium was
      ciliated columnar, metaplastic squamous or of mature squamous type. Thyroid
      epithelium was only rarely present (11%). FNA is only moderately sensitive for a
      preoperative evaluation of TDC. Cytomorphologic features are not unique; however,
      in the right clinicoradiologic setting should lead to an accurate diagnosis.
      Abundant colloid, most often with ciliated columnar epithelium, is the
      predominant cytopathologic finding. Thyroid epithelium is rarely identified.
      Differential diagnosis involves branchial cleft cyst, lymphoepithelial cyst,
      thyroid gland lesions, and lymphadenopathy (of various etiologies).

PMID- 16299738
TI  - Contralateral metastasis of a cutaneous Merkel cell carcinoma: diagnosis by fine
      needle aspiration cytology.

PMID- 16299739
TI  - Atypical squamous cells in exfoliative urinary cytology: clinicopathologic
      correlates.
AB  - Presence of atypical squamous cells (ASC) in voided urine is an uncommon finding
      that may be the harbinger of an underlying malignant process. ASCs in urine may
      precede a de novo histologic diagnosis of malignancy or be the first sign of a
      recurrence in the lower urinary tract, or the gynecologic tract (in women). This
      study analyzed all urine cytology specimens with such diagnoses, with reference
      to their final histologic outcome. All urine cytology cases (n = 17,446) that
      included ASCs, evaluated at The Johns Hopkins Hospital between 1989 and 2003 (14
      yr), were reviewed for diagnoses. ASCs as defined in this study are keratinizing
      cells with large and hyperchromatic smudgy nuclei, high N/C ratio, abnormal
      nuclear or cytoplasmic shapes, and densely orangeophilic cytoplasm. These cases
      lacked the qualitative and quantitative criteria for malignancy. The final
      reference outcome was determined by subsequent histologic and clinical follow-up.
      Of these 17,446 urine specimens, 55 cases (0.3%) from 47 patients had ASCs
      present. Thirty-two of the 47 patients had adequate follow-up. In 8 of these 32
      patients (25%), a diagnosis of squamous-cell carcinoma (SCC) of the urinary
      bladder or urothelial carcinoma (UC) with squamous differentiation was made on
      subsequent histologic examination. In two cases (6%) a diagnosis of high-grade
      cervical SCC was established on subsequent follow-up. Twenty two of 32 cases
      (69%) remained benign on histologic and prolonged clinical follow-up. We conclude
      that ASCs in urine are rare (0.3% in this series). An interpretation of ASCs in a
      urine specimen is made when there is insufficient qualitative/quantitative
      evidence for a carcinoma diagnosis. ASCs in urine are a clinically valid
      diagnostic category (31% were later diagnosed with SCC). Most patients with
      urinary ASCs do not develop malignancy and, therefore, these cells may represent
      a reactive/inflammatory process most commonly due to vaginal contamination (in
      women) or exfoliation from the distal urethra (in men). Rarely, ASCs may
      exfoliate from a uterine cervical SCC and, therefore, a pelvic examination should
      be considered in such patients.

PMID- 16299740
TI  - Periosteal chondromyxoid fibroma: a case study using imprint cytology.
AB  - Bone surface is an exceptional location for chondromyxoid fibroma. Only 14 cases
      of juxtacortical chondromyxoid fibroma have been reported to date and, to our
      knowledge, none of these cases are documented with imprint cytology. We report a
      case of periosteal chondromyxoid fibroma located in the distal tibial metaphysis
      of a 4-yr-old boy. The clinical diagnosis was metaphyseal fibrous defect.
      Cytologic examination revealed a mixoid matrix, with stellate and spindle-shaped
      cells seen singly, focus of chondroid material, and epithelioid cells.
      Multinucleate giant cells were not seen. The diagnosis of periosteal
      chondromyxoid fibroma can be made by fine-needle aspiration or imprint cytology
      with clinico-radiologic correlation.

PMID- 16299741
TI  - Esophageal carcinoma with a rhabdoid phenotype: a case report of diagnosis by
      endoscopic ultrasound-guided fine-needle aspiration.
AB  - Malignant extra renal tumors with rhabdoid phenotype are aggressive neoplasms
      associated with a poor prognosis. These tumors have been reported in soft tissue
      and various organs including the gastrointestinal tract. We report one of such
      tumors arising in the esophagus and discuss the cytopathologic,
      immunohistochemical, and ultrastructural features. Endoscopic ultrasound-guided
      fine-needle aspiration (FNA) cytology revealed a highly cellular tumor,
      consisting of polygonal poorly cohesive cells with prominent eosinophilic
      paranuclear cytoplasmic inclusions. Immunohistochemical staining showed strong
      cytoplasmic positivity for vimentin and cytokeratin. Electron microscopy revealed
      presence of numerous intermediate filaments. To the best of our knowledge, this
      is the first example of carcinoma with rhabdoid phenotype of the esophagus
      diagnosed by FNA cytology.

PMID- 16299742
TI  - Fine-needle aspiration cytology of epithelioid angiosarcoma: a diagnostic
      dilemma.
AB  - A 28-year-old woman with a 2-yr history of unilateral chronic leg swelling,
      initially thought to be secondary to deep vein thrombosis, later thought to be
      due to congenital venous malformation, eventually developed a pelvic mass, which
      was biopsied by fine-needle aspiration. On the basis of cytologic features on
      smears, high-grade sarcoma was reported. The patient underwent surgery to resect
      the pelvic mass, which showed anastomosing vascular channels arising from
      external iliac vein in histology. However, the tumor cells unexpectedly showed
      strong and diffuse immunohistochemical expression of cytokeratin and epithelial
      membrane antigen. The case was sent for expert consultation, and the expert's
      opinion was epithelioid angiosarcoma. The expert's diagnosis was confirmed 2 yr
      later by local recurrence. The clinical presentation, cytology, histology, and
      immunohistochemistry of the current case and 15 other cases of epithelioid
      angiosarcoma found in the cytology literature are summarized. This case
      illustrates that morphology with clinicopathologic correlation tends to be a
      better guide than available special techniques.

PMID- 16299743
TI  - A two-stage analysis of repeated measurements with dropouts and/or intermittent
      missing data.
AB  - This article is about a simple two-stage analysis that utilizes slope
      coefficients as the dependent variable for testing the significance of difference
      in mean rates of change in repeated measurement designs with missing data. The
      ANCOVA test on the doubly weighted slope coefficients provides power comparable
      to that of more complex maximum likelihood procedures when data are missing
      completely at random, requires fewer assumptions and is more generally applicable
      under realistic nonrandom dropout conditions, and most importantly can be readily
      understood and explained by those who actually do most controlled clinical
      research.

PMID- 16299744
TI  - Detection of Her-2/neu oncogene in breast carcinoma by chromogenic in situ
      hybridization in cytologic specimens.
AB  - Determination of Her-2/neu oncogene amplification is important in the current
      treatment of breast carcinoma. In addition to fluorescence in situ hybridization
      (FISH) and immunohistochemical stain (HercepTest), chromogenic in situ
      hybridization (CISH) has been shown to be a sensitive and specific method to
      determine the Her-2/neu status of surgical specimens. The effectiveness of CISH
      in detecting the Her-2/neu oncogene in cytologic specimens has not been well
      documented. Twenty-five cases of fine needle aspirate smears and touch imprints
      from infiltrating ductal carcinomas were examined. Both CISH and FISH were
      performed on each case using a digoxigenin-labeled Her-2 DNA probe for CISH
      (Zymed) and both Her-2 and chromosome 17 probes for FISH (Vysis). Sixty tumor
      cells were evaluated in each case. The scoring system and interpretation of CISH
      were as follows: (1) no amplification (<5 brown dots/nucleus), (2) amplification
      (>10 brown dots/nucleus), and (3) low-level amplification (5-9 brown
      dots/nucleus). Of the 25 cases analyzed, 23 (3 amplified and 20 nonamplified)
      showed similar results for both methods. Two cases were discordant. In these
      cases, low-level amplification was suggested by CISH but nonamplification by
      FISH. One of the cases can be explained by polysomy for chromosome 17 by FISH. In
      conclusion, our preliminary data suggest that CISH is a useful technique to
      determine Her-2/neu oncogene status in cytologic specimens. In a case of low
      level amplification, a CISH chromosome 17 probe should be used, or FISH is
      recommended for confirmation.

PMID- 16299745
TI  - Pemphigus vulgaris of the cervix.

PMID- 16299746
TI  - Pleomorphic adenoma of the breast: case report and review of the literature.
AB  - Pleomorphic adenoma of the breast (PAB) is a very rare neoplasm. Although quite
      unique in its morphology, PAB shares some similarities with adenomyoepithelioma
      and is considered by some authors as a variant of this entity. Cytologic
      diagnosis of this lesion can be very challenging, especially when limited
      sampling is available. The differential diagnosis of PAB includes metaplastic
      carcinoma. On cytologic material, fibroadenoma and phyllodes tumor should also be
      considered within the differential diagnosis. We report the findings in a case of
      PAB, initially misdiagnosed as mucinous carcinoma on fine-needle aspiration, and
      review the literature regarding this entity. Correct identification of this
      benign mammary neoplasm is important to avoid unnecessarily aggressive treatment.

PMID- 16299747
TI  - Resolving ASCUS without recourse to HPV testing: manual reprocessing of residual
      automated liquid-based cytology (ALBC) material using manual liquid-based
      cytology (MLBC).
AB  - We show that residual cell material from ThinPrep PapTest (Cytyc Corporation,
      Boxborough, MA) atypical squamous-cells of undetermined significance (ASCUS)
      cases may be manually reprocessed to triage women into actionable diagnostic
      categories (HSIL, LSIL, and Negative). Material remaining from each of 358
      ThinPrep ASCUS cases was manually reprocessed as two slides, labeled "A" and "B."
      Interobserver agreement between case contributors (CCs) and three sequential
      reviewers (SRs) was analyzed with 186 cases (Study 1), and diagnostic
      reproducibility between SRs was examined with an additional 172 cases (Study 2).
      In Study 1, CCs classified 33% of cases as LSIL or greater, SRs classified 60% as
      LSIL or greater, and there was 58% diagnostic agreement between CCs and SRs. No
      "Negative" case assignment by one group afforded an "HSIL" assignment by the
      complementary group. In Study 2, there was 95% agreement between SRs A slide and
      B slide diagnoses with 54% of A slides and 55% of B slides classified as LISL or
      greater. Again, no "Negative" case assignment to one slide afforded an "HSIL"
      assignment to the complementary slide. Overall, 12.6% of the 358 cases showed
      HSIL, and all HSILs by one observer group were ASCUS or greater by the
      complementary observer group. Using manual reprocessing beyond the 21-day
      specimen outdate for HPV testing by the Hybrid Capture II High Risk HPV test (HR
      HCII; Digene Corporation, Beltsville, MD), many ThinPrep ASCUS cases were
      reclassified as LSIL or HSIL. The 12.6% HSIL proportion of this study
      approximated the 11.5% CIN 2 or greater proportion of the ALTS ASCUS arm. Similar
      to ALTS, manual liquid-based cytology (MLBC) would have referred nearly 60% of
      women to colposcopy for a definitive diagnosis of HSIL or LSIL without resorting
      to HPV testing. These data demonstrate that many cases of automated liquid-based
      cytology (ALBC)-diagnosed ASCUS represent unrecognized SIL, which is present in
      the ALBC specimen vial at the time the ASCUS diagnosis is rendered.

PMID- 16299748
TI  - Quality assurance in cervical screening of a high risk population: a study of
      65,753 reviewed cases in Parana Screening Program, Brazil.
AB  - Epidemiological data from the Quality Assurance Unit (QAU) of the Cervical Cancer
      Screening Program of Parana is discussed. Slides (65,753) reviewed by the QAU,
      from October 1997 to July 1999, were analyzed. Relations between agreement rate,
      diagnostic categories, and age groups were tested. The overall agreement rate was
      97.04% (kappa +/- 95%, confidence interval = 0.888 +/- 0.003). Low-grade squamous
      intraepithelial lesion (LSIL) showed its peak prevalence in patients < or = 19 yr
      (8.3%). High-grade squamous intraepithelial lesion (HSIL) was more common in
      women between 40 and 49 yr (5.0%). Squamous-cell carcinoma (SCC) was almost
      exclusively seen in women > or = 40 yr. The lowest agreement rates were seen in
      adenocarcinoma (54.5%; kappa = 0.667) and LSIL cases (76.3%, kappa = 0.822), and
      in women < or = 19 yr (95.8%). It was concluded that constant monitoring to
      assess specific errors allows directed measures. The 10% rescreening model of
      quality assurance proved to be effective in a low resources setting with a
      positive overall financial impact.

PMID- 16299749
TI  - Paired ductal lavage and fine-needle aspiration specimens from patients with
      breast carcinoma.
AB  - Ductal lavage (DL) is a new procedure for sampling of the mammary epithelium, but
      experience with this technique remains limited. We compared the findings in
      paired DL and fine-needle aspiration (FNA) specimens obtained from patients with
      breast carcinoma. Four reviewers evaluated all DL samples. Two reviewers also
      examined the FNA material and compared cellular composition and morphologic
      findings in paired samples. DL and FNA samples from six patients were
      satisfactory for evaluation. Two DL samples showed marked atypia, one showed mild
      atypia, and two were benign; there was no agreement in one case (mild atypia vs.
      benign). Overall, the atypical cells in DL samples resembled those in the paired
      FNA material, but low degree of cytologic atypia and relative paucity of atypical
      cells limited their correct identification. The interpretation of DL samples is
      more challenging than that of FNA material, but similar criteria apply. To
      increase the sensitivity of DL, the number of epithelial cells required for a
      satisfactory sample should be higher than previously set.

PMID- 16299750
TI  - Cytomorphology of gastric and duodenal epithelium and reactivity to B72.3: a
      baseline for comparison to pancreatic lesions aspirated by EUS-FNAB.
AB  - Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) has become
      a widely used method of pre-operatively evaluating pancreatic masses. This
      technique introduces gastrointestinal contamination into the specimen, which
      poses a diagnostic pitfall. The cytomorphologic features of these contaminants
      have not been fully characterized. The current study was designed to
      systematically document the cytomorphology of gastric and duodenal epithelium on
      fixed and air-dried smears, as well as ThinPrep (TP) preparations, and to assess
      the reactivity of the epithelial cells to the tumor marker B72.3 so as to
      establish a baseline for future comparative studies with EUS-FNAB of the
      pancreas. Air-dried and fixed smears and TP specimens were obtained using a
      cytobrush from gastric (GM) and duodenal (DM) mucosa from 14 Whipple specimens.
      Cytologic features of cell architecture, cellular features and smear background
      were analysed. Immunocytochemical staining with B72.3 was performed in 10/14
      cases. Mucin was present in all preparations except one case from the duodenum.
      It was consistently present as isolated thick to thin clumps but never as diffuse
      'colloid-type' mucin; it was most prominent on air-dried smears, and most
      abundant from the GM. Epithelial cells were admixed with mucin, but degenerated
      cells and inflammation were not present within the mucin. Mucin on TP appeared as
      fragmented wisps of pale blue staining material. Background inflammation and
      debris were not significant findings. The epithelial cells were arranged in large
      and small monolayered sheets. Smaller groups were more common from GM on smears
      and more abundant on TP than smears. Luminal edges (DM>GM) were a prominent
      feature, with a brush border noted in DM. The nuclei of GM and DM were round,
      evenly spaced and without atypia, and dense, non-vacuolated cytoplasm was the
      rule, with the exception of goblet cells and occasional gastric foveolar cells
      noted in one case. In both GM and DM, B72.3 stained goblet cells with a strong,
      coarsely granular pattern and stained epithelial cells focally in a finely
      granular, punctate, perinuclear distribution; mucin also stained strongly in all
      cases. These baseline characteristics provide a template for assessing mucin and
      epithelial GM and DM contamination on pancreatic EUS-FNAB specimens.

PMID- 16299751
TI  - Technical evaluation of the new thin layer device CellSlide (Menarini
      Diagnostics).
AB  - The CellSlide Processor (Menarini Diagnostics) is an automatic computer
      controlled instrument, designed to prepare standardized, thin-layer cytological
      preparations using a filtration process. In this report, this new processor has
      been tested in a multicentric investigation, designed to evaluate cell recovery,
      cellular morphology and possible time saved in reading the slide. The results of
      this study show that the CellSlide processing system is suitable for use in the
      preparation of liquid-based gynaecology samples. Furthermore, the high-quality
      smear produced by the CellSlide decreases the reading time by approximately 20
      25%.

PMID- 16299752
TI  - Blastomyces associated with granulomatous inflammation in a bronchial lavage.

PMID- 16299755
TI  - Confirmatory factor analysis of a short form of the Coping Inventory for
      Stressful Situations.
AB  - The 48-item Coping Inventory for Stressful Situations (CISS) was designed to
      assess three dimensions (task-oriented, emotional, and avoidant) of self-reported
      responses to stressful circumstances, but results from factor analyses suggest
      four factors. The present research used confirmatory factor analysis to verify
      the four-factor structure for the 21-item CISS short form in samples of 1,628
      undergraduate students and 390 community-dwelling adults. Factors corresponding
      to task-oriented and emotional scales were orthogonal and were well defined by
      their seven constituent items. The avoidant scale was split into two three-item
      parcels that describe specific avoidance behaviors (contact a friend and treat
      oneself) rather than broad response categories. In the undergraduate sample,
      depression and anxiety correlated negatively with the task-oriented scale and
      positively with the emotional scale. In the community sample, the emotional scale
      was positively correlated with neuroticism and negatively correlated with
      extroversion and agreeableness, whereas the task-oriented scale was negatively
      correlated with neuroticism and positively correlated with extroversion,
      openness, agreeableness, and conscientiousness. It was concluded that the task
      oriented and emotional scales have potential as measures of two types of
      responses to routine stressors.

PMID- 16299756
TI  - Regulating the regulator: the control of auxin transport.
AB  - With the discovery of the phytohormone auxin in the late 1920s, it became
      possible to link the regulation of complex plant growth responses to a single
      biologically active compound. Among all the plant growth regulators characterised
      so far, only auxin appears to be actively transported throughout the plant to
      create complex variations in concentration patterns and flow directions over
      time. This stimulated interest in the specific mechanisms underlying auxin
      transport as key factors in plant growth responses. Research in the last decade
      revealed several genes involved in the controlled transport of auxin and greatly
      improved our understanding of the basic principles of auxin-mediated responses.
      We are at this point, however, only starting to understand the complex interplay
      and control of factors that ultimately underlie the observed spatiotemporal
      variations in auxin transport and thus mediate plant growth and environmental
      responses. This review highlights important findings that provide us with a
      framework of molecular players and potential regulatory mechanisms that should
      contribute to the formulation of a comprehensive dynamic model of spatiotemporal
      auxin distribution.

PMID- 16299757
TI  - Stochastic gene expression, disruption of tissue averaging effects and cancer as
      a disease of development.
AB  - Despite the extensive literature describing the somatic genetic alterations in
      cancer cells, the precise origins of cancer cells remain controversial. In this
      article, I suggest that the etiology of cancer and the generation of genetic
      instability in cancer cells should be considered in the light of recent findings
      on both the stochastic nature of gene expression and its regulation at tissue
      level. By postulating that gene expression is intrinsically probabilistic and
      that stabilization of gene expression arises by cellular interactions in
      "morphogenetic fields", development and cellular differentiation can be rethought
      in an evolutionary perspective. In particular, this article proposes that
      disruptions of cellular interactions are the initial source of abnormal gene
      expression in cancer cells. Consequently, cancer phenotypes such as genetic and
      epigenetic instabilities, and also the presence of cells with stem cell-like
      properties, may result from inaccurate and aberrant patterns of gene expression
      generated by microenvironmental alterations. Finally, the therapeutic
      implications of this view are discussed.

PMID- 16299758
TI  - My favorite animal, Trichoplax adhaerens.
AB  - Trichoplax adhaerens is more simply organized than any other living metazoan.
      This tiny marine animal looks like a irregular "hairy plate" ("tricho plax") with
      a simple upper and lower epithelium and some loose cells in between. After its
      original description by F.E. Schulze 1883, it attracted particular attention as a
      potential candidate representing the basic and ancestral state of metazoan
      organization. The lack of any kind of symmetry, organs, nerve cells, muscle
      cells, basal lamina and extracellular matrix originally left little doubt about
      the basal position of T. adhaerens. Nevertheless, the interest of zoologists and
      evolutionary biologists suddenly vanished for more than half a century when
      Trichoplax was claimed to be an aberrant hydrozoan planula larva. Recently,
      Trichoplax has been rediscovered as a key species for unraveling early metazoan
      evolution. For example, research on regulatory genes and whole genome sequencing
      promise insights into the genetics underlying the origin and development of basal
      metazoan phyla. Trichoplax offers unique potential for understanding the minimal
      requirements of metazoan animal organization.

PMID- 16299759
TI  - Evolution of behaviour: bridging the gap between evolutionary and developmental
      genetics.

PMID- 16299760
TI  - The conceptual challenge of systems biology.

PMID- 16299761
TI  - TIRs of joy: new receptors for auxin.
AB  - Back-to-back papers have described the identification of a family of receptors
      for the plant hormone auxin. Most developmental processes in plants are dependent
      on auxin signalling making this discovery a landmark in the search for the
      mechanism of auxin action. The TIR1 gene translates into a protein with
      recognised motifs including an F-box domain and TIR1 forms part of an important
      ubiquitination complex that tags other proteins for degradation. Specific amongst
      the targets of TIR1 are a set of auxin-regulated transcription factors. The
      latest work has shown that TIR1 itself is also the binding site for auxin making
      it an auxin receptor with no requirement for a biochemical signalling cascade.

PMID- 16299762
TI  - Long-range coordination of planar polarity in Drosophila.
AB  - The mechanisms by which cells become polarised in the plane of an epithelium have
      been studied in Drosophila for many years. Work has focussed on two key
      questions: firstly, how individual cells adopt a defined polarity, and secondly
      how the polarity of each cell within a tissue is aligned with its neighbours. It
      has been established that asymmetric subcellular localisation of a number of
      polarity proteins is an essential mechanism underlying polarisation of single
      cells. The process by which this polarity is coordinated between cells however is
      less well understood, but is thought to involve gradients of activity of the
      atypical cadherins Dachsous and Fat. Subsequently, this long-range polarity
      signal is refined by local cell-cell interactions involving the transmembrane
      molecules Frizzled, Strabismus and Flamingo. The role of these factors in
      coordinating polarity will be discussed.

PMID- 16299763
TI  - Memory mechanisms of active transcription during cell division.
AB  - The developmental programs of eukaryotic organisms involve the programmed
      transcription of genes. A characteristic gene expression pattern is established
      and preserved in each different cell type. Therefore, gene activation at a
      particular time and its maintenance during cell division are significant for
      cellular differentiation and individual development. Although many studies have
      sought to explain the molecular mechanisms of gene expression regulation, the
      mechanism through which gene expression states are inherited during cell division
      has not been fully elucidated yet. This review illustrates the general principles
      and the complexities involved in the establishment and maintenance of active
      transcription through cell cycles. It focuses on the most-recent findings about
      the ways in which molecular memory marks for active transcription are coordinated
      with cell cycle events, such as replication, mitosis and nuclear organization, to
      mediate transcription memory across cell division events, which may establish a
      unifying memory process of active transcription.

PMID- 16299764
TI  - The Y chromosome as a target for acquired and amplified genetic material in
      evolution.
AB  - The special properties of the Y chromosome stem form the fact that it is a non
      recombining degenerate derivative of the X chromosome. The absence of homologous
      recombination between the X and the Y chromosome leads to gradual degeneration of
      various Y chromosome genes on an evolutionary timescale. The absence of
      recombination, however, also favors the accumulation of transposable elements on
      the Y chromosome during its evolution, as seen with both Drosophila and mammalian
      Y chromosomes. Alongside these processes, the acquisition and amplification of
      autosomal male benefit genes occur. This review will focus on recent studies that
      reveal the autosome-acquired genes on the Y chromosome of both Drosophila and
      humans. The evolution of the acquired and amplified genes on the Y chromosome is
      also discussed. Molecular and comparative analyses of Y-linked repeats in the
      Drosophila melanogaster genome demonstrate that there was a period of their
      degeneration followed by a period of their integration into RNAi silencing, which
      was beneficial for male fertility. Finally, the function of non-coding RNA
      produced by amplified Y chromosome genetic elements will be discussed.

PMID- 16299765
TI  - Different species problems and their resolution.
AB  - At least three different issues are commonly referred to by the term "the species
      problem": one concerns the necessary properties of species, a second the
      processes responsible for the existence of species, and a third methods for
      inferring species limits. Solutions have recently been proposed to the first two
      problems, which are conceptual in nature (the third is methodological). The first
      equates species with metapopulation lineages and proposes that existence as a
      separately evolving metapopulation lineage be considered the only necessary
      property of species. The second views the species category as a cluster concept
      and proposes that no single process or set of processes be considered necessary
      for the existence of species. Although these two solutions have been portrayed as
      being in conflict, they are, in fact, highly compatible. Moreover, the proposals
      in question clarify the problem concerning methods for inferring the limits of
      species, which has for a long time been confused with the problem concerning the
      necessary properties of species. Together these proposals provide the opportunity
      for biology to move beyond debates about the definition of the species category
      and focus on estimating the boundaries and numbers of species as well as studying
      the diverse processes involved in their origin and persistence.

PMID- 16299766
TI  - Fundamental issues in systems biology.
AB  - In the context of scientists' reflections on genomics, we examine some
      fundamental issues in the emerging postgenomic discipline of systems biology.
      Systems biology is best understood as consisting of two streams. One, which we
      shall call 'pragmatic systems biology', emphasises large-scale molecular
      interactions; the other, which we shall refer to as 'systems-theoretic biology',
      emphasises system principles. Both are committed to mathematical modelling, and
      both lack a clear account of what biological systems are. We discuss the
      underlying issues in identifying systems and how causality operates at different
      levels of organisation. We suggest that resolving such basic problems is a key
      task for successful systems biology, and that philosophers could contribute to
      its realisation. We conclude with an argument for more sociologically informed
      collaboration between scientists and philosophers.

PMID- 16299767
TI  - The epigenetic basis for embryonic stem cell pluripotency.
AB  - As well as having the remarkable ability to differentiate into all of the cell
      types in the embryo, embryonic stem (ES) cells also have the capacity to divide
      and self-renew. Maintenance of pluripotency through repeated cell divisions
      indicates that the developmental plasticity of ES cells has a specific epigenetic
      basis. We propose that tightly localised regions of histone modification are
      formed in ES cells by binding of sequence-specific transcription factors at genes
      that are destined for expression at later stages of differentiation. These 'early
      transcription competence marks' would help to maintain pluripotency by preventing
      the spread of repressive chromatin modifications. We further propose that the
      presence of discrete histone modification marks in pluripotent cells facilitates
      the binding of lineage-specific and general transcription factors to the marked
      regions as ES cells commit to different fates. By helping to organise the
      precisely timed responses of genes to the signals that determine lineage choice,
      the gene-specific localised epigenetic marks would play a key role in the
      establishment of complex gene expression programmes in differentiating cells.

PMID- 16299768
TI  - Coevolution theory of the genetic code: is the precursor-product hypothesis
      invalid?

PMID- 16299769
TI  - Global analysis of siRNA-mediated transcriptional gene silencing.
AB  - The RNAi machinery is not only involved with post-transcriptional degradation of
      messenger RNAs, but also used for targeting of chromatin changes associated with
      transcriptional silencing. Two recent papers determine the global patterns of
      gene expression and chromatin modifications produced by the RNAi machinery in
      fission yeast.(9, 10) The major sites include the outer centromere repeats, the
      mating-type locus and subtelomeric regions. By comparison, studies of Arabidopsis
      heterochromatin also implicate transposons as a major target for silencing.
      Analyses of siRNA libraries from Drosophila, nematodes and Arabidopsis indicate
      that major repeats at centromeres, telomeres and transposable elements are likely
      targets of RNAi. Also, intergenic regions are implicated as targets in
      Arabidopsis.

PMID- 16299770
TI  - The innovation triad: an EvoDevo agenda.
AB  - This article introduces a special issue on evolutionary innovation and
      morphological novelty, two interrelated themes that have received a remarkable
      increase of attention over the past few years. We begin with a discussion of the
      question of whether innovation and novelty represent distinct evolutionary
      problems that require a distinct conceptualization. We argue that the mechanisms
      of innovation and their phenotypic results--novelty--can only be properly
      addressed if they are distinguished from the standard evolutionary themes of
      variation and adaptation, and we present arguments for making such a distinction.
      We propose that origination, the first formation of biological structures, is
      another distinct problem of morphological evolution, and that together with
      innovation and novelty it constitutes a conceptual complex we call the innovation
      triad. We define a problem agenda of the triad, which separates the analysis of
      the initiating conditions from the mechanistic realization of innovation, and we
      discuss the theoretical problems that arise from treating innovation as distinct
      from variation. Further, we categorize the empirical approaches that address
      themes of the innovation triad in recognizing four major strands of research: the
      morphology and systematics program, the gene regulation program, the epigenetic
      program, and the theoretical biology program. We provide examples of each
      program, giving priority to contributions in the present issue. In conclusion, we
      observe that the innovation triad is one of the defining topics of EvoDevo
      research and may represent its most pertinent contribution to evolutionary
      theory. We point out that an inclusion of developmental systems properties into
      evolutionary theory represents a shift of explanatory emphasis from the external
      factors of natural selection to the internal dynamics of developmental systems,
      complementing adaptation with emergence, and contingency with inherency.

PMID- 16299771
TI  - Lentiviral-mediated gene transfer of brain-derived neurotrophic factor is
      neuroprotective in a mouse model of neonatal excitotoxic challenge.
AB  - Excitotoxicity may be a critical factor in the formation of brain lesions
      associated with cerebral palsy. When injected into the murine neopallium at
      postnatal day 5, the glutamatergic analog N-methyl-D-aspartate (NMDA) produces
      transcortical neuronal death and periventricular white matter cysts, which mimic
      brain damage observed in human term and preterm neonates at risk for developing
      cerebral palsy. We previously showed that intracerebral injection of brain
      derived neurotrophic factor (BDNF) was neuroprotective in this model. Because
      BDNF does not easily cross the blood-brain barrier, alternative strategies to
      avoid repeated intracerebral injections of BDNF should be tested, particularly
      when the goal of such translational research is ultimately to achieve clinical
      application. The goal of the present study was to assess the protective role of
      lentiviral-mediated gene transfer of BDNF against excitotoxic lesions induced by
      NMDA in newborn mice. We first assessed the biological activity of BDNF gene
      transfer in vitro and determined the efficiency of gene transfer in our in vivo
      model. We next administered the BDNF-expressing vector by intracerebral injection
      in neonatal mice, 3 days before inducing NMDA lesions. When compared with a
      control green fluorescent protein-expressing lentiviral vector, administration of
      BDNF-expressing vector induced a significant protection of the periventricular
      white matter and cortical plate against the NMDA-mediated insult.
      Intraventricular delivery of the BDNF-expressing lentiviral vector was more
      efficient in terms of neuroprotection than the intraparenchymal route.
      Altogether, the present study shows that viral-mediated gene transfer of BDNF to
      newborn mouse brain is feasible and affords significant neuroprotection against
      an excitotoxic insult.

PMID- 16299772
TI  - Stabilization of Taq DNA polymerase at high temperature by protein folding
      pathways from a hyperthermophilic archaeon, Pyrococcus furiosus.
AB  - Pyrococcus furiosus, a hyperthermophilic archaeon growing optimally at 100
      degrees C, encodes three protein chaperones, a small heat shock protein (sHsp), a
      prefoldin (Pfd), and a chaperonin (Cpn). In this study, we report that the
      passive chaperones sHsp and Pfd from P. furiosus can boost the protein refolding
      activity of the ATP-dependent Cpn from the same hyperthermophile. The thermo
      stability of Taq polymerase was significantly improved by combinations of P.
      furiosus chaperones, showing ongoing protein folding activity at elevated
      temperatures and during thermal cycling. Based on these results, we propose that
      the protein folding apparatus in the hyperthermophilic archaeon, P. furiosus can
      be utilized to enhance the durability and cost effectiveness of high temperature
      biocatalysts.

PMID- 16299773
TI  - Expression and identification of a new splice variant of neuroglycan C, a
      transmembrane chondroitin sulfate proteoglycan, in the human brain.
AB  - Neuroglycan C (NGC) is a transmembrane chondroitin sulfate proteoglycan with an
      EGF module. We studied the expression of NGC in the human brain, mainly in the
      hippocampus, and confirmed some observations by conducting experiments using rat
      brain. In humans, NGC mRNA was expressed exclusively in the brain, especially in
      the immature brain. The telencephalon, including the hippocampus and neocortex,
      showed strong mRNA expression. NGC was immunolocalized to neuropils in the
      hippocampus and neocortex of the adult rat. RT-PCR experiments showed that four
      splice variants (NGC-I, -II, -III, and -IV) were expressed in the adult human
      hippocampus. By Western blotting, the expression as proteins of all splice
      variants except NGC-II was confirmed in the adult rat hippocampus. NGC-IV, which
      was first found in the present study, had the shortest cytoplasmic domain among
      the four variants. NGC-IV mRNA was expressed by neurons, but not by astrocytes,
      in culture prepared from the fetal rat hippocampus, suggesting that NGC-IV plays
      a role specific to neurons. In addition, the human NGC gene, which is registered
      as CSPG5, comprised six exons and was approximately 19 kb in size. In exon 2, a
      single nucleotide polymorphism resulting in Val188Gly in the NGC ectodomain was
      observed.

PMID- 16299774
TI  - Characterizing the conformational ensemble of monomeric polyglutamine.
AB  - Studies of synthetic polyglutamine peptides in vitro have established that
      polyglutamine peptides aggregate via a classic nucleation and growth mechanism.
      Chen and colleagues [Proc Natl Acad Sci U S A 2002;99:11884-11889] have found
      that monomeric polyglutamine, which is a disordered statistical coil in solution,
      is the critical nucleus for aggregation. Therefore, nucleation of beta-sheet-rich
      aggregates requires an initial disorder to order transition, which is a highly
      unfavorable thermodynamic reaction. The questions of interest to us are as
      follows: What are the statistical fluctuations that drive beta-sheet formation in
      monomeric polyglutamine? How do these fluctuations vary with chain length? And
      why is this process thermodynamically unfavorable, that is, why is monomeric
      polyglutamine disordered? To answer these questions we use multiple molecular
      dynamics simulations to provide quantitative characterization of conformational
      ensembles for two short polyglutamine peptides. We find that the ensemble for
      polyglutamine is indeed disordered. However, the disorder is inherently different
      from that of denatured proteins and the average compactness and magnitude of
      conformational fluctuations increase with chain length. Most importantly, the
      effective concentration of sidechain primary amides around backbone units is
      inherently high and peptide units are solvated either by hydrogen bonds to
      sidechains or surrounding water molecules. Due to the multiplicity of backbone
      solvation modes the probability associated with any specific backbone
      conformation is small, resulting in a conformational entropy bottleneck which
      makes beta-sheet formation in monomeric polyglutamine thermodynamically
      unfavorable.

PMID- 16299775
TI  - Energetics and stability of transmembrane helix packing: a replica-exchange
      simulation with a knowledge-based membrane potential.
AB  - The energetics and stability of the packing of transmembrane helices were
      investigated by Monte Carlo simulations with the replica-exchange method. The
      helices were modeled with a united atom representation, and the CHARMM19 force
      field was employed. Based on known experimental structures of membrane proteins,
      an implicit knowledge-based potential was developed to describe the helix
      membrane interactions at the residue level, whose validity was tested through
      prediction of the orientations when single helices were inserted into a membrane.
      Two systems were studied in this article, namely the glycophorin A dimer, and
      helices A and B of Bacteriorhodopsin. For the glycophorin A dimer, the most
      stable structure (0.5 A away from the experimental structure) is mainly
      stabilized by the favorable helix-helix interactions, and has the most population
      regardless of the helix-membrane interaction. However, for helices A and B of
      Bacteriorhodopsin, it was found that the packing determined by helix-helix
      interactions is nonspecific, and a native-like structure (0.2 A from the
      experimental one) can be identified from several structural analogs as the most
      stable one only after applying the membrane potential. Our results suggest that
      the contribution from the helix-membrane interaction could be critical in the
      correct packing of transmembrane helices in the membrane.

PMID- 16299776
TI  - Similarity networks of protein binding sites.
AB  - An increasing attention has been dedicated to the characterization of complex
      networks within the protein world. This work is reporting how we uncovered
      networked structures that reflected the structural similarities among protein
      binding sites. First, a 211 binding sites dataset has been compiled by removing
      the redundant proteins in the Protein Ligand Database (PLD) (http://www
      mitchell.ch.cam.ac.uk/pld/). Using a clique detection algorithm we have performed
      all-against-all binding site comparisons among the 211 available ones. Within the
      set of nodes representing each binding site an edge was added whenever a pair of
      binding sites had a similarity higher than a threshold value. The generated
      similarity networks revealed that many nodes had few links and only few were
      highly connected, but due to the limited data available it was not possible to
      definitively prove a scale-free architecture. Within the same dataset, the
      binding site similarity networks were compared with the networks of sequence and
      fold similarity networks. In the protein world, indications were found that
      structure is better conserved than sequence, but on its own, sequence was better
      conserved than the subset of functional residues forming the binding site.
      Because a binding site is strongly linked with protein function, the
      identification of protein binding site similarity networks could accelerate the
      functional annotation of newly identified genes. In view of this we have
      discussed several potential applications of binding site similarity networks,
      such as the construction of novel binding site classification databases, as well
      as the implications for protein molecular design in general and computational
      chemogenomics in particular.

PMID- 16299777
TI  - Methyl dynamics for understanding hydrophobic core packing of dynamically
      different motifs of double-stranded RNA binding domain of protein kinase R.
AB  - Double-stranded RNA binding domains of human protein kinase R (dsRBD-PKR)
      regulate distinct cellular functions and the fate of an RNA molecule in the cell.
      This highly homologous domains present in multiple copies in a number of species,
      exhibit individual and specific functional specificity. Number of NMR and X-ray
      crystallographic structural studies reveals that such domains take a common alpha
      beta-beta-beta-alpha tertiary fold. However, the functional specificities of
      these domains could be due to the dynamics of the individual amino acid residues,
      as has been shown earlier in the case of backbone dynamics of 15N-1H of dsRNA
      binding motifs (dsRBMs) of human protein kinase R (PKR) (Nanduri S, Rahman F,
      Williams BRG, Qin J. EMBO J 2000;19:5567-5574). To further investigate if the
      differences in dynamics of the two dsRBMs are restricted to only backbone, or if
      the side-chain motions are also different to the extent of influencing their
      packing of the two hydrophobic cores, we have investigated the methyl group
      dynamics using 13C-methyl relaxation measurements. The results show that the
      hydrophobic core of dsRBM1 is more tightly packed than dsRBM2, and it seems to
      undergo less fast scale motions in the subnanosecond regime.

PMID- 16299779
TI  - On the kinetics and mechanism of the reaction of cysteine and hydrogen peroxide
      in aqueous solution.

PMID- 16299780
TI  - Recent advances in the management of esophageal adenocarcinoma.

PMID- 16299781
TI  - Differences and similarities of adenocarcinomas of the esophagus and
      esophagogastric junction.
AB  - During the last few decades there has been an alarming rise in the incidence of
      tumors originating at the esophagogastric junction (EGJ) [1]. The reason for this
      is unknown. Tumors of the EGJ can be categorized in two types of cancer divided
      according to their anatomical origin: distal esophageal adenocarcinoma and
      adenocarcinoma of the gastric cardia. However, due to their location, in the
      transitional zone of the esophagus and stomach, there is constant debate about
      the proper classification, staging, and management of these tumors. The etiology
      of distal esophageal adenocarcinoma is clearly related to gastroesophageal reflux
      disease (GERD) and the development of a Barrett's esophagus [2]. The etiology of
      adenocarcinoma of the gastric cardia is less well understood. In the present
      paper, we will discuss the clinical characteristics and clinical management of
      esophagogastric tumors. Special attention will be given to differences and
      similarities of adenocarcinomas of the gastric cardia and distal esophagus.

PMID- 16299782
TI  - Diagnostic and therapeutic endoscopy.
AB  - Within the gastrointestinal tract, there is no shorter segment with a higher
      cancer incidence than the gastro-esophageal junction. Flexible endoscopy is the
      mainstay for diagnosis of early and advanced esophageal adenocarcinoma, for the
      treatment of early lesions, and also for the palliation of advanced cancer. New
      developments in endoscopy aim to improve the diagnosis and treatment of
      esophageal cancer. These include high resolution and magnification endoscopy in
      combination with chromendoscopy, and techniques based on modulation of the
      features of light bundles, such as narrow band imaging, fluorescence endoscopy,
      and elastic scattering spectroscopy. The value of these techniques for the
      surveillance of distal esophageal neoplasia needs further study. Furthermore, new
      methods of tissue sampling and evaluation are being studied to augment
      identification and staging of patients at risk for cancer. Finally, newer
      instruments may decrease patient burden during endoscopy, making screening and
      surveillance more acceptable from a patient's perspective. This review discusses
      the new developments in flexible endoscopy for diagnosis and therapy of early and
      advanced and advanced esophageal adenocarcinoma.

PMID- 16299783
TI  - Surgical techniques.
AB  - Adenocarcinoma of the esophagus and gastroesophageal junction (GEJ) has shown a
      remarkable increase during recent decades. Most patients are present with
      advanced stage disease, reflecting transmural growth and metastasis to lymph
      nodes at the time of diagnosis. Moreover, the pattern of lymph node dissemination
      is chaotic and difficult to predict, and despite the use of modern technology
      (e.g., spiral CT, EUS, FDG-PET), clinical staging remains suboptimal. These
      shortcomings in staging, as well as in different attitudes toward extent of
      resection and lymphadenectomy, are reflected by a great variation in surgical
      techniques, which are discussed in this review. As to the results, primary
      surgery can currently be performed with low mortality, below 5% in high volume
      centers. Hospital mortality and morbidity are mainly related to pulmonary
      complications and anastomotic leaks, the latter mostly resolving under
      conservative treatment. Overall 5-year survival varies between 10% and 59%. As
      expected the most important prognostic determinants are completeness of resection
      (R0 vs. R1-R2) and lymph node status (N0, N1). R0 resection currently offers 5
      year survival rates of over 40%. Five-year survival figures for node-negative
      (N0) patients exceed 70%, and even for node-positive (N1), patients reach 25%. It
      is not known whether performing a three-field lymph node dissection is beneficial
      for patients with adenocarcinoma of the distal esophagus. With overall 5-year
      survival currently exceeding 30%-40%, these figures should be the gold standard
      against which all other therapeutic modalities are compared.

PMID- 16299784
TI  - Radiation and chemoradiation therapy for esophageal adenocarcinoma.
AB  - The aims of preoperative chemoradiation therapy (preop-CRT) for esophageal
      adenocarcinoma are to reduce incomplete local resection (R1,R2), local and
      systemic recurrences that are reported in up to 30% of patients who undergo
      surgery alone. Phase II studies of preop-CRT, with radiation doses in the 40-50
      Gy range, and concurrent chemotherapy with 5-fluorouracil (5-FU)-cisplatin +/-
      paclitaxel, or cisplatin-paclitaxel, have reported subsequent RO resection rates
      of 80%-100%, with tumor sterilization achieved in 8%-49% of cases, and
      consequently improved local control. New chemotherapy regimens omitting 5-FU have
      reduced the incidence of severe esophagitis, unplanned hospitalization, with
      comparable efficacy. Among three randomised trials that compared preop-CRT to
      surgery alone, one shown a debatable survival advantage. Reducing local
      recurrence rates lead to a switch to more distant failures, and increasing the
      radiation dose beyond 45 Gy appears to be of little value. However, it should be
      remembered that preop-CRT has associated toxicity, and may increase postoperative
      mortality. Novel strategies, which include induction with chemotherapy followed
      by preop-CRT, and for radiation therapy, three dimensional conformation
      techniques, image fusioning, and improved definition of treatment volumes, are
      still considered experimental and should be tested in specialized centers.

PMID- 16299785
TI  - Novel molecular targeted therapy for esophageal cancer.
AB  - Esophageal cancers are highly lethal neoplasms which are generally refractory to
      conventional multidisciplinary interventions. Recent elucidation of the
      mechanisms of esophageal carcinogenesis, as well as preclinical studies utilizing
      chromatin remodeling agents and inhibitors of oncogene signaling in conjunction
      with conventional chemotherapeutic agents provide new opportunities for the
      development of potentially efficacious molecular targeted therapies for these
      malignancies.

PMID- 16299786
TI  - Epidemiology of esophageal adenocarcinoma.
AB  - The incidence of esophageal adenocarcinoma has risen rapidly over the past 25
      years in the United States as well as in several Western European countries. This
      increase had been most dramatic among white males. The majority of these cancers
      arise from a background of premalignant Barrett esophagus. However, less than 10%
      of the patients with esophageal adenocarcinoma were known to have Barrett
      esophagus previously. It is uncertain which risk factors contribute to the
      increasing incidence of esophageal adenocarcinoma, although gastroesophageal
      reflux disease, cigarette smoking, and obesity have been implicated. Whereas
      infection with Helicobacter pylori and use of non-steroidal anti-inflammatory
      drugs are associated with reduced risk, low intakes of fruit, vegetables, and
      cereal fibers seem to increase the risk of esophageal adenocarcinoma. Presently
      there is no evidence that strongly supports any specific strategy to screen a
      subgroup of the population at risk for Barrett esophagus and adenocarcinoma of
      the esophagus.

PMID- 16299787
TI  - The molecular biology of esophageal adenocarcinoma.
AB  - BACKGROUND: Barrett's esophagus is an acquired metaplastic change that occurs in
      the distal esophagus secondary to chronic gastroesophageal reflux. This
      premalignant condition forms the most important risk factor for developing
      esophageal adenocarcinoma, which is an extremely aggressive tumor with a 5-year
      survival rate of less than 25%. Carcinomas that arise in the setting of Barrett's
      esophagus are thought to develop as part of the metaplasia-dysplasia-carcinoma
      sequence. OBJECTIVE: To review the current knowledge on the genomic alterations
      involved in the development of Barrett's esophagus and its progression to
      dysplasia and/or cancer. RESULTS: Several changes in gene structure, gene
      expression, and protein structure are associated with the progression of
      Barrett's esophagus to adenocarcinoma. Accumulation of these changes seems to be
      essential, rather than the exact sequence of these changes. Multiple molecular
      pathways are involved and interact with each other. Alterations in tumor
      suppressor genes, amongst which p53 and p16, are early events in the metaplasia
      dysplasia-adenocarcinoma sequence, followed by loss of cell cycle checkpoints.
      Ongoing genomic instability leads to cumulative genetic errors and thereby the
      generation of multiple clones of transformed cells. CONCLUSIONS: Within the
      multistep process of esophageal adenocarcinogenesis, to date no single molecular
      marker came forward able to predict who will and who will not develop cancer in
      the setting of Barrett's esophagus. Instead, panels of markers need to be
      developed in the future allowing to indicate disease progression. Identification
      of crucial molecular pathways involved in esophageal adenocarcinogenesis would
      ultimately improve therapy and facilitate development of new treatment
      strategies.

PMID- 16299789
TI  - Surgery for early stage esophageal adenocarcinoma.
AB  - Current treatment recommendations for early esophageal adenocarcinoma range from
      radical esophagectomy with extensive lymphadenectomy, limited surgical resection
      with/without regional lymphadenectomy to endoscopic mucosectomy or ablation. A
      comparison of treatment associated morbidity, tumor recurrence rates, and
      functional outcome suggests that none of these alternatives can be universally
      recommended. Rather, an individualized strategy should be employed based on depth
      of tumor penetration into the mucosa/submucosa, presence of lymph node
      metastases, multicentricity of tumor growth, length of the underlying Barrett
      mucosa and comorbidity of the affected patient. Endoscopic mucosectomy may
      suffice for an isolated focus of high-grade neoplasia or mucosal cancer, provided
      the neoplasia and underlying Barrett mucosa can be removed completely. Surgical
      resection is the treatment of choice for tumors invading the submucosa,
      multicentric tumors and recurrence after endoscopic mucosectomy. The extent of
      surgical resection must be guided by the length of the Barrett mucosa. In most
      instances a complete tumor resection and removal of the entire Barrett mucosa can
      be achieved by a limited transabdominal approach, and therefore subtotal
      esophagectomy may not be necessary. Application of the sentinel node technology
      may in the future allow to limit systematic lymphadenectomy to the rather small
      subgroup of patients who in fact have lymph node metastases.

PMID- 16299788
TI  - Diagnostic radiology and nuclear medicine.
AB  - The diagnosis and accurate staging of esophageal adenocarcinoma remains one of
      the greatest challenges for non-invasive imaging techniques. All modalities have
      limitations and require a rational application of combined tools in order to
      assess the extent of loco-regional tumor and distant metastatic disease. The
      fundamental role remains defining organ-confined disease and mapping non-organ
      confined disease. Endoscopic ultrasound combined with multislice computed
      tomography (CT) is the mainstay of morphologic loco-regional staging. In recent
      years, functional metabolic 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)
      positron emission tomography (PET) has emerged as a particularly useful adjunct
      to detect occult metastatic disease, to predict response to neoadjuvant therapy
      and to document recurrent disease. The current imaging algorithm and new
      developments in imaging assessment will be reviewed.

PMID- 16299790
TI  - Neoadjuvant and adjuvant chemotherapy for esophageal adenocarcinoma.
AB  - The poor outcome associated with surgical resection alone for most patients with
      locoregional esophageal cancer has generated intensive investigation of combined
      modality treatment approaches that include systemic chemotherapy. This review
      discusses the current role of chemotherapy in the treatment of patients with
      adenocarcinoma of the esophagus, given in either the pre-operative (neoadjuvant)
      or post-operative (adjuvant) setting compared to surgery alone, highlighting the
      results of large, randomized clinical trials that included patients with
      adenocarcinoma of the esophagus as well as some of the approaches being evaluated
      with novel therapies in earlier phase clinical trials. Although no definitive
      recommendations for pre-operative or post-operative treatment can be made for
      patients with adenocarcinoma of the esophagus based on outcomes reported in
      randomized clinical trials performed to date, the results from these trials
      suggest chemotherapy or chemoradiation in the peri-operative period may have
      benefit, especially in certain sub-groups. Newer, more effective agents are
      needed as well as methods to identify which tumors will respond to therapy.
      Improvement in outcomes for patients with this disease will require rigorous
      evaluation of newer multi-modality regimens in well-designed and appropriately
      powered clinical trials.

PMID- 16299791
TI  - Palliative therapy.
AB  - There are a wide variety of palliative treatments for esophageal cancer. The aim
      of most treatments is to maintain oral food intake, which should stabilize or
      even improve quality of life. Stent placement is currently the most widely used
      treatment modality for palliation of dysphagia from esophageal cancer. Stent
      placement offers a rapid relief of dysphagia, however, the rate of complications
      (late hemorrhage) and recurrent dysphagia (stent migration, tumor overgrowth) is
      relatively high. The scientific evidence to advocate the use of anti-reflux
      stents for the prevention of gastro-esophageal reflux is currently too low.
      Photodynamic therapy is mostly used in North America; however, due to the high
      costs of the treatment, the long-lasting side effects and the necessity of
      repeated treatments, it is not an ideal treatment for palliation of malignant
      dysphagia. Nd:YAG laser is a relatively effective and safe treatment modality,
      although laser treatment is also expensive, technically difficult and requiring
      repeated treatment sessions at 4-6 weeks intervals. Single dose brachytherapy
      compares favorably to stent placement in long-term effectiveness and safety.
      Effective treatment strategies are probably 12 Gy given in one fraction or 16 Gy
      given in two fractions. Palliative chemotherapy offers response rates in recent
      trials (including partial and complete responses) ranging from 35% to 50%.
      Whether palliative chemotherapy also results in a survival benefit is not
      established yet. For clinical trials on palliation of esophageal cancer, the
      measurement of quality of life is an important outcome measure. The cancer
      specific EORTC QLQ-C30 and the esophageal cancer-specific EORTC-OES-18 are
      validated measures for establishing quality of life status. For the future, a
      multimodality approach with stent placement or brachytherapy in combination with
      chemotherapy may be indicated.

PMID- 16299792
TI  - Improving outcomes after esophagectomy: the impact of operative volume.
AB  - Once considered an uncommon malignancy, primary esophageal adenocarcinoma has
      increased steadily in incidence over the past three decades. Despite advances in
      multimodality therapy, the prognosis for this tumor is generally poor. Surgical
      resection and reconstruction of the upper gastrointestinal tract is the current
      standard of care for localized esophageal cancer, but despite advances in
      perioperative care, still remains a relatively high-risk surgical procedure.
      Increasing numbers of reports published over the past decade have documented a
      clear volume-outcome relationship for several complex surgical procedures, and in
      particular for esophagectomy. The clinical implications of this association are
      reviewed in this section.

PMID- 16299793
TI  - Courageous challenge: Clinical intestinal transplantation.

PMID- 16299794
TI  - Predictive markers for postsurgical recurrence of hepatocellular carcinoma.

PMID- 16299795
TI  - Molecular mechanisms of hepatic metastasis in colorectal cancer.

PMID- 16299796
TI  - Radiochemotherapy with Vinblastine, Methotrexate, and Bleomycin in the treatment
      of verrucous carcinoma of the head and neck.
AB  - OBJECTIVE: To explore whether the combined radiochemotherapy with Vinblastine,
      Methotrexate, and Bleomycin could be an effective alternative treatment to
      surgery in verrucous carcinoma (VC) of the head and neck. METHODS: Combined
      radiochemotherapy was used in 12 patients with previously untreated VC. They were
      irradiated to equivalent tumor dose of 44-70 Gy (median, 56 Gy) and had > or = 2
      courses of concomitant chemotherapy. Chemotherapy regimen consisted of prolonged
      intravenous infusions of Vinblastine 2 mg (day 1); Methotrexate 50 mg (day 2);
      Bleomycin 15 mg (days 2 and 3), and repetition at 2-3 week intervals. RESULTS:
      Eleven of 12 patients were cured of VC, and one died of purulent meningitis
      associated with intracranial extension of VC from the oral cavity. Of 11 patients
      cured of VC, eight had advanced tumors. The median follow-up of cured patients
      was 3.6 years (range, 1.4-13.6 years). All the patients developed mucositis of
      grade > or = 3, whereas no serious late side-effects were recorded. CONCLUSIONS:
      Combined radiochemotherapy with Vinblastine, Methotrexate, and Bleomycine is
      highly effective in the treatment of VC of the head and neck. It could be
      successfully used in the patients with inoperable VC or as an alternative to
      surgery.

PMID- 16299797
TI  - Primary angiosarcoma of the spleen.
AB  - BACKGROUND AND OBJECTIVES: Primary splenic angiosarcoma is a very rare and
      aggressive neoplasm with a high metastatic rate and dismal prognosis. Since only
      a few cases have been adequately reported in the medical literature, we report
      here a further six cases. METHODS: The records of all cases of primary splenic
      angiosarcoma treated at Chang Gung Memorial Hospital from April 1991 to July 2004
      were retrospectively reviewed. RESULTS: Of the six cases identified (three men
      and three women; range, 7-69 years; median, 44 years), four presented with
      palpable abdominal masses or left upper quadrant abdominal pain. Other systemic
      symptoms, such as bleeding gums, fatigue, fever, body weight loss, and
      gastrointestinal bleeding were noted. An abnormal hematogram was found in five
      patients, with all of these five showing anemia, and three thrombocytopenia.
      Splenomegaly was present in all patients. Hemoperitoneum due to splenic rupture
      was noted in one patient. Three patients had distant metastasis to the liver (n =
      2), bone (n = 1), bone marrow (n = 1), and small bowel (n = 1) at diagnosis.
      Liver (n = 3), bone (n = 1), and bone marrow (n = 1) metastases were found in
      four patients after initial therapy. Five of the six cases underwent a
      splenectomy, one underwent partial hepatectomy, and one received chemotherapy.
      The respective 1-, 3- and 5-year survival rates were 60%, 40%, and 40%, and the
      median survival time was 36 months. One patient was disease-free 162 months after
      splenectomy. CONCLUSIONS: The clinical presentations of splenic angiosarcoma were
      similar to those of previous reports apart from the higher rate of splenomegaly
      observed in this study. In contrast to reported pediatric cases, our patient
      achieved long-term disease-free survival after splenectomy alone.

PMID- 16299798
TI  - Expression of angiogenic VEGF-A (soluble isoforms 121, 165) and lymphangiogenic
      VEGF-C in colorectal cancers with micro-satellite instability.
AB  - BACKGROUND AND OBJECTIVES: Colorectal cancers (CRC) with high-level micro
      satellite instability (MSI-H) show reduced metastatic potential and better
      prognosis compared to stage-matched stable (MSS) cancers.
      Angiogenesis/lymphangiogenesis, central to tumour growth and spread, is mediated
      by vascular endothelial growth factor (VEGF) cytokines, but little is known of
      their relationship to MSI. METHODS: In this study, 67 sporadic CRC with
      identified MSI status, and 8 samples of normal colon were analysed for VEGF-A
      soluble isoforms (VEGF-121/VEGF-165) and VEGF-C gene transcription (by RT-PCR and
      scanning densitometry), and blood vessel density (BVD; measuring angiogenesis)
      and VEGF-C protein expression (measuring lymphangiogenesis). RESULTS: Compared to
      normal colon, VEGF-165 transcription was reduced (P < 0.05), but VEGF-121
      transcription was higher in MSS (P < 0.06) and MSI-L (P < 0.01) cancers (but
      similar in MSI-H). VEGF-165 transcription was unrelated to MSI, but VEGF-121
      transcription was elevated in MSI-L (P < 0.06). There was a weak inverse
      correlation with VEGF-121 transcription and Dukes stage (P < 0.09), and with BVD
      and MSI (P < 0.09). With a singular di-nucleotide loci mutation (MSI-L), VEGF-121
      (P < 0.03) and VEGF-C (P < 0.04) transcription was elevated. CONCLUSIONS: MSI-H
      cancers have reduced angiogenic/lymphangiogenic potential, and transcription of
      VEGF-121 may be important in early growth and spread of CRC. Elevated VEGF-121
      and VEGF-C transcription with singular di-nucleotide mutations may aid in the
      identification of distinct MSI-L cancers.

PMID- 16299799
TI  - Overexpression of PIM-1 is a potential biomarker in prostate carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Prostate carcinoma (CaP) is the frequently diagnosed
      cancer in man. Prostate specific antigen (PSA), which is now widely used as a
      diagnostic marker for CaP, lacks specificity and fails to predict possible CaP
      progression. So it is necessary to identify the new biomarkers for CaP. METHOD:
      We identified several genes that were differentially expressed between benign
      prostatic hyperplasia and CaP by microarray analysis. One gene that was
      overexpressed encoded a serine/threonine kinase PIM-1. Reverse transcription
      polymerase chain reaction (RT-PCR) and immunohistochemical analysis were used to
      investigate PIM-1 mRNA and protein expression in malignant and benign prostate
      samples. RESULT: PIM-1 was overexpressed in CaP, and the overexpression of PIM-1
      was related to the grade and neoplastic transformation of CaP. CONCLUSIONS: The
      data, together with the molecular functions of PIM-1 suggest that PIM-1 may have
      an important role in CaP progression and has potential to be a diagnostic and
      prognostic marker for CaP.

PMID- 16299801
TI  - Morpheaform extra-ocular sebaceous carcinoma.
AB  - BACKGROUND: Sebaceous carcinoma is an unusual, aggressive, malignant tumor
      derived from the epithelium of sebaceous glands. It may arise in ocular or extra
      ocular sites and is often evident as an ulcerated or non-ulcerated cystic nodule
      measuring up to 8 cm in diameter. A significant number of extra-ocular sebaceous
      carcinomas have been associated with metastases and high mortality rate. METHODS
      AND RESULTS: We reviewed the literature in the context of our report of a 68-year
      old woman who had a morpheaform plaque of the upper lip of 15 years duration,
      extending into the left naso-genal groove, which histologically also showed
      marked stromal fibrosis. Three years after excision, there were no signs of
      recurrence or metastases. CONCLUSIONS: This patient is unusual in clinical and
      histologic pattern, as a morpheaform appearance has only been described
      previously in only one sebaceous carcinoma. In addition, no metastatic disease 15
      years after tumor onset is a fortunate and remarkable feature.

PMID- 16299800
TI  - Growth index, assessed with Ki-67 and ssDNA labeling; a significant
      prognosticator for patients undergoing curative resection for hepatocellular
      carcinoma.
AB  - BACKGROUND AND OBJECTIVES: The aggressiveness and greater malignant potential of
      cancers are characterized by several biological phenomena such as accelerated
      growth invasiveness, and the ability to form distant metastasis. Thus, knowledge
      of such biological difference may be a more accurate prognosticator for cancer
      patients. Tumor growth depends on the degree of imbalance between cell production
      and loss. This study aimed to clarify a possible role for the modified
      prognosticator, growth index (GI); defined as the difference between Ki-67 (%)
      and single-stranded DNA (ssDNA) (%) labeling indices, in patients undergoing
      curative resection for hepatocellular carcinoma (HCC). METHODS: Tissue specimens
      were obtained from 40 HCC patients who underwent curative surgery.
      Immunohistochemical staining was performed using the avidin-biotin-peroxidase
      complex method. RESULTS: The GI in HCC ranged from -1.90% to 28.65%, median 3.73.
      GI was related to histologic grade, intrahepatic metastasis, and pathologic T
      stage. Cumulative survival was poorer in patients with higher GI (> or = median
      value). Multivariate analysis demonstrated that GI is an independent
      prognosticator along with vascular invasion and intrahepatic metastasis.
      CONCLUSIONS: The higher GI values were significantly associated with histologic
      aggressive features of HCCs, and GI was a significant independent prognosticator
      in HCC patients after curative resection.

PMID- 16299802
TI  - cDNA microarray-based translational research in soft tissue sarcoma.
AB  - The authors discuss application of cDNA microarray technology in translational
      research to identify diagnostic markers and therapeutic targets in adult soft
      tissue sarcoma. Recent results in synovial sarcoma are used to highlight the
      applicability of this technology for marker and target discovery, as well as the
      need for preclinical validation of putative therapeutic targets.

PMID- 16299803
TI  - Intestinal transplantation for the treatment of neoplastic disease.
AB  - BACKGROUND: Authors reviewed single center experience of intestinal
      transplantation for treatment of intra-abdominal neoplastic disease. METHODS:
      There were 25 auto- or allograft transplantations in 21 patients; desmoid tumor
      (14), neuroendocrine tumor (2), adenocarcinoma (2), hemangioma (1), lymphoma (1),
      and solid pseudopapillary tumor (1). Medical records were reviewed for cause of
      graft loss and mortality, recurrent neoplasm, and quality of life. Survival was
      analyzed using Kaplan-Meier method. RESULTS: There were 11 graft losses;
      mortality with functioning graft (6), ischemic necrosis (2), acute or chronic
      rejection (2), and arterial thrombosis (1) during 38 months of mean follow-up.
      Seven patients died because of recurrent neoplasm and transplant related
      complications. Six patients experienced recurrent disease; three desmoid tumor
      (3/14), two adenocarcinoma (2/2), and one neuroendocrine tumor (1/2). Recurrent
      desmoid tumors were successfully treated with simple excision. Patient and graft
      survival in the desmoid tumor are 69.2% and 50.0% at 5 years after transplant.
      Among 14 survivors, 2 need parenteral nutrition or intravenous hydration. Twelve
      patients are working full time. CONCLUSIONS: Intestinal transplantation is a
      reasonable life-saving treatment for catastrophic intra-abdominal neoplastic
      diseases.

PMID- 16299804
TI  - Non-axillary breast cancer recurrences after sentinel node biopsy.
AB  - BACKGROUND AND OBJECTIVES: The primary lymphatic pathway of patients with breast
      cancer is toward the axilla, but lymph drainage is also possible towards the
      internal mammary chain and the supraclavicular fossa. In the current article, the
      development of breast cancer recurrences at these two sites after sentinel lymph
      node biopsy is reviewed. METHODS: Since 1997, 803 patients underwent sentinel
      lymph node biopsy with intratumoral injection of 99mTc-nanocolloid and patent
      blue dye in The Netherlands Cancer Institute. All sentinel nodes as visualized on
      the lymphoscintigraphy images were pursued. The patients were followed
      prospectively for a median period of 34 months. Patients with a lymph node
      recurrence outside the axilla were identified and their lymphatic mapping
      procedures were reviewed. RESULTS: Four of the 803 patients (0.5%) developed
      regional lymph node recurrences outside the axilla. One recurrence was located in
      the internal mammary chain, the other three in the supraclavicular bed. One or
      two of these patients also had an axillary recurrence. The sentinel node
      procedure had failed in two of the four patients. CONCLUSION: The incidence of
      nodal recurrences outside the axilla is low. Although all extra-axillary sentinel
      nodes were pursued, some of these recurrences concern missed sentinel nodes that
      harbor metastasis. Identification of all sentinel nodes and subsequent treatment
      of the involved basins may reduce the risk of breast cancer recurrences in these
      unusual locations.

PMID- 16299805
TI  - Detection of infraclavicular lymph node metastases using ultrasonography in
      breast cancer.
AB  - BACKGROUND AND OBJECTIVES: As infraclavicular lymph node metastases is one of the
      parameters of stage III-C, the diagnostic techniques aiming to identify the
      metastases of this region have gained importance recently. In this study, we
      investigated the presence of axillary and infraclavicular lymph node metastases
      with ultrasonography. METHODS: Axillary and infraclavicular lymph nodes were
      evaluated by preoperative ultrasonography in 100 consecutive breast cancer
      patients. Median age was 47 (23-76) years. RESULTS: Ultrasonography identified
      lymph nodes correlating with metastases in the infraclavicular region in 20
      patients. In 19 of these patients, metastases were verified in the lymph nodes
      with histopathologic examination (false positivity rate 5%). Of the 80 patients
      who were not considered as having metastases by ultrasonography, 59 had no
      metastatic lymph nodes on histological examination. The specificity of
      ultrasonography in the identification of metastatic lymph nodes in the
      infraclavicular region was 98.3%, with a sensitivity of 47.5%, positive
      predictive value of 95%, negative predictive value of 73.7%, and overall accuracy
      of 78%. CONCLUSIONS: Patients who were identified to have infraclavicular lymph
      node metastases by preoperative ultrasonographic examination should have a
      relevant treatment plan as they are classified as locally advanced, stage III-C
      disease.

PMID- 16299806
TI  - Loss of E-cadherin mRNA and gain of osteopontin mRNA are useful markers for
      detecting early recurrence of HCV-related hepatocellular carcinoma.
AB  - BACKGROUND AND OBJECTIVES: We investigated whether expression of E-cadherin (E
      cad) and osteopontin (OPN) mRNAs could predict the early recurrence of HCV
      associated hepatocellular carcinoma (HCV-HCC) after curative surgery. METHODS:
      Forty-four HCV-HCC patients who underwent curative hepatectomy were divided into
      three categories: category 1--recurrence (3 mR+: n = 6) or non-recurrence (3 mR-:
      n = 38) within 3 months; category 2--recurrence (6 mR+: n = 4) or non-recurrence
      (6 mR-: n = 34) between 3-6 months; category 3--recurrence (1 yR+: n = 4) or non
      recurrence (1 yR-: n = 30) between 6-12 months. Levels of expression of E-cad and
      OPN mRNAs were analyzed quantitatively by real-time PCR and calculated using the
      formula: t = (copy of E-cad or OPN/copy of GAPDH) x 1,000. RESULTS: The t-value
      for E-cad was significantly lower in 3 mR+ than in 3 mR- (0.4 and 28.1, P <
      0.05), in 6 mR+ than in 6 mR- (4.0 and 30.6, P < 0.05), and in 1 yR+ than in 1 yR
      (9.2 and 32.9, respectively, P < 0.05). The t-value for OPN was higher in 3 mR+
      than in 3 mR- (92.6 and 65.7, P = 0.57), in 6 mR+ than in 6 mR- (457.1 and 58.15,
      respectively, P = 0.24), and in 1 yR+ than in 1 yR- (221.8 and 53.5,
      respectively, P = 0.06). CONCLUSIONS: Low expression of E-cad mRNA and high
      expression of OPN mRNA are associated with a higher likelihood of early
      recurrence of HCV-HCC.

PMID- 16299807
TI  - Molecular mechanisms of hepatic metastasis in colorectal cancer.
AB  - BACKGROUND: Colorectal cancer currently accounts for 11% of all cancers in the
      United States and is the second leading cause of cancer-related death, with the
      majority of deaths attributable to hepatic metastases. Many new studies are
      elucidating the complex molecular factors involved in this event, which could be
      used to generate clinically applicable screening and therapeutic tools. METHODS:
      An initial Pubmed and Medline literature search using keywords such as, molecular
      factor, colorectal cancer, hepatic metastasis/es, and main headings, such as
      angiogenesis, was reviewed. Since there are many molecular factors involved in
      this process not all could be included in this review. The list of discussed gene
      products was limited to the most studied factors, identified by the number of
      references in the literature search, and additional recently discovered gene
      products with in-vivo evidence of strong metastasis association. RESULTS: Twenty
      molecular factors were identified and included in the discussion of this review
      article. The molecular factors were separated into four groups based on their
      function, they are: proteolysis, adhesion, angiogenesis, and cell survival. All
      factors have a promising role as a screening or therapeutic target. CONCLUSION:
      This review has identified the many recent advances in elucidating the pathways
      involved in colorectal cancer hepatic metastasis. By better understanding the
      many complex molecular events involved in metastasis, novel screening and
      therapeutic tools may be developed with the ultimate goal of preventing
      metastasis and increasing patient survival.

PMID- 16299808
TI  - Expression of pro-apoptotic (p53, p21, bax, bak and fas) and anti-apoptotic (bcl
      2 and bcl-x) proteins in serous versus mucinous borderline ovarian tumours.
AB  - BACKGROUND: We examined the expression of apoptosis-related proteins in serous
      versus mucinous borderline ovarian tumours, in comparison with benign and
      malignant ovarian tumours. MATERIALS AND METHODS: Immunohistochemical expression
      of pro-apoptotic (p53, p21, bax, bak, fas) and anti-apoptotic proteins (bcl-2,
      bcl-x) was determined in 34 borderline (19 mucinous, 15 serous), 20 benign (10
      mucinous, 10 serous) and 28 malignant ovarian tumours (9 mucinous, 19 serous).
      RESULTS: A difference in semi-quantitative p53 expression was found between
      benign and borderline tumours (P = 0.01), but not between borderline and
      malignant tumours. Increased p21 expression was found in borderline versus benign
      tumours (P = 0.004). Bcl-2 expression was lower in borderline than in benign (P =
      0.01) and malignant tumours (P = 0.02). No difference in bax, bak, fas or bcl-x
      expression was observed among the three tumour types. Higher percentage of p21
      positive cells was found in serous than in mucinous borderline tumours (P <
      0.001). Bcl-2 expression was higher in serous than in mucinous forms of benign (P
      < 0.001), borderline (P < 0.001), and malignant tumours (P < 0.003). No
      difference in p53, bax, bak, fas or bcl-x expression was observed between serous
      and mucinous borderline ovarian tumours. CONCLUSION: Although p53 overexpression
      was a common feature of both mucinous and serous borderline tumours, p21 and bcl
      2 overexpression appeared specific to serous tumours.

PMID- 16299809
TI  - Age dependent phosphorylation and deregulation of p53 in human vestibular
      schwannomas.
AB  - Tumor-specific alterations at the p53 gene locus in 30 human vestibular
      schwannomas (VS) comprising 10 confirmed NF2 cases and 20 sporadic cases were
      analyzed. We found loss of heterozygosity (LOH) at the first intron of the p53
      gene locus in 54% of the informative cases. This is the first report showing LOH
      at the p53 gene locus in a significant number of human VS and both sporadic and
      NF2 cases show the LOH event. Increased levels of normal size p53 mRNA and p53
      protein were found in all the tumors analyzed. Thus p53 appears to be deregulated
      in all the tumors suggesting that p53 alterations may be associated with tumor
      progression in VS. There was a negative significant correlation of patients' age
      and percentage of Ser 392 phosphorylated p53 protein. The tumor samples obtained
      from younger patients of 35 yr and below showed higher percentage of Ser 392
      phosphorylated p53 protein compared to the tumors of older patients. The
      increased percentage of Ser 392 phosphorylated p53 protein indicates that it
      could be involved in the acceleration of tumor growth in the younger patients.
      Our results suggest that age dependent phosphorylation of p53 protein and
      deregulation of p53 gene has a role in the development of human vestibular
      schwannomas.

PMID- 16299810
TI  - Co-regulation of B-Myb expression by E2F1 and EGF receptor.
AB  - Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is
      frequently over-expressed in human cancers and is associated with tumorigenesis,
      and increased tumor proliferation and progression. Also found in breast tumors
      with high levels is B-Myb, a transcription factor whose expression is activated
      by E2F1/3 at the late G1 phase and the level is sustained through the S phase.
      Recent reports suggest a casual correlation between EGFR and B-Myb expression in
      primary breast carcinomas. However, the mechanism for such co-expression remains
      un-investigated. Here, we report that EGFR is important for B-Myb expression and
      the underlying mechanism involves cooperated effects from EGFR and E2F1. EGF
      stimulation and forced expression of EGFR significantly increase B-Myb gene
      activity and such increase occurs in the G1 phase. EGF-induced B-Myb expression
      was not significantly suppressed following inhibition of PI-3K and ERK, two major
      EGFR downstream pathways. In contrast, we observed EGF-induced in vivo
      association of nuclear EGFR to the B-Myb promoter and the association is only
      detected at the G1/S phase and is abolished by EGFR kinase inhibitor. As EGFR
      lacks DNA-binding domain but contains transactivational activity and E2F1
      activates B-Myb expression in the G1/S phase, we further reasoned that nuclear
      EGFR might cooperate with E2F1 leading to activation of B-Myb. Indeed, we found
      that EGFR co-immunoprecipitated with E2F1 in an EGF-dependent manner and that EGF
      activated in vivo binding of E2F1 to the B-Myb promoter. Consistently, forced
      expression of both EGFR and E2F1 in EGFR-null CHO cells greatly enhanced B-Myb
      promoter activity, compared to the vector control and expression of EGFR or E2F1
      alone. Promoter mutagenesis studies showed that EGF-induced activation of B-Myb
      promoter required both E2F and EGFR target sites. In summary, our data suggest
      that deregulated EGFR signaling pathway facilitate tumor cell proliferation
      partly via EGFR interaction with E2F1 and subsequent activation of B-Myb gene
      expression.

PMID- 16299811
TI  - Molecular analysis of hprt mutations generated in Chinese hamster ovary EM9 cells
      by uranyl acetate, by hydrogen peroxide, and spontaneously.
AB  - Naturally occurring uranium and depleted uranium (DU) are believed to be health
      hazards by virtue of both their chemical and radiological properties. The
      mechanism(s) behind uranium's chemotoxic effects has yet to be elucidated.
      Previous work has shown that DU, as uranyl acetate (UA), was mutagenic at the
      hypoxanthine (guanine) phosphoribosyltransferase (hprt) locus in XRCC1-deficient
      CHO EM9 cells. The purpose of the current study was to characterize the mutations
      induced by UA at the hprt locus of CHO EM9 cells and compare the mutation
      spectrum of UA with those of hydrogen peroxide and spontaneous mutations in the
      same line. The hypothesis being tested was that if DU as UA is chemically
      genotoxic then the mutation spectrum induced by the heavy metal should be
      distinct from that produced spontaneously or by H2O2. A total of 59 UA-induced,
      38 spontaneous, and 45 H2O2-induced mutations were identified. Base substitutions
      comprised 29%, 42%, and 16% of UA, spontaneous, and H2O2 mutants, respectively.
      The frequency of G --> T or C --> A substitutions was not significantly different
      in spontaneous or H2O2-induced mutants than in UA-induced mutants, suggesting a
      possible role for 8-oxodG damage in UA mutagenesis. However, the observation that
      UA produced significantly more major genomic rearrangements (multiexon insertions
      and deletions) than occurred spontaneously suggests the possibility that DNA
      strand breaks or crosslinks could also be UA-induced mutagenic lesions. The
      unique mutation spectrum elicited by exposure to UA suggests that UA generates
      mutations in ways that are different from spontaneous and free radical as well as
      radiological mechanisms.

PMID- 16299813
TI  - How do the prevalences of urogenital symptoms change during pregnancy?
AB  - AIM: The aim of this study was to report the changes in prevalences of urogenital
      symptoms during pregnancy and to evaluate the amount of bother nulliparous
      pregnant women experience from these symptoms. METHODS: We have used a
      prospective longitudinal cohort study design. Five hundred fifteen nulliparous
      women with a singleton pregnancy were recruited from 10 midwifery practices
      between January 2002 and July 2003. The women received postal questionnaires.
      Urogenital symptoms were assessed with the Dutch version of the standardized and
      validated Urogenital Distress Inventory (UDI). We analyzed our data on item level
      and on the clustering of items. RESULTS: The prevalences of the frequency and
      urgency symptoms are high at 12 weeks (74% and 63%) and remain stable during
      pregnancy. The prevalences of urinary incontinence and voiding difficulties
      increase with gestational age. Frequency disappears in 12% in late pregnancy,
      urgency in 22%, and stress incontinence in 23%. The prevalence of bothersome
      frequency symptoms is much higher than of urinary incontinence (21% compared to
      6%). All UDI subscales increase significantly during pregnancy. CONCLUSIONS:
      Urogenital symptoms occur in almost all women during pregnancy. Whereas the
      prevalence of overactive bladder symptoms is high and remains stable from early
      pregnancy on, the prevalences of urinary incontinence symptoms increase with
      gestational age. Despite the high prevalences of symptoms, the majority of women
      report not to be bothered by it.

PMID- 16299812
TI  - Genistein affects androgen-responsive genes through both androgen- and estrogen
      induced signaling pathways.
AB  - This study examined the mechanisms by which the prostate cancer chemopreventive
      agent genistein modulates gene expression in LNCaP human prostate cancer cells.
      Expression of androgen- and estrogen-regulated genes was measured in LNCaP cells
      cultured in the presence or absence of hormonal stimulation and the presence or
      absence of genistein. Genistein strongly suppressed basal expression of androgen
      responsive gene (ARG) mRNAs, including prostate-specific antigen (PSA) and Ste20
      related proline-alanine-rich kinase (SPAK). However, genistein had little or no
      effect on basal expression of two other ARGs, beta2-microglobulin (B2M) or
      selenoprotein P (SEPP1). Culturing LNCaP cells in the presence of the synthetic
      androgen R1881-induced increases in PSA, SPAK, B2M, and SEPP1 mRNA levels. The
      R1881-induced expression of these genes was uniformly blocked by genistein. For
      PSA and SPAK, genistein also blocked or downregulated 17beta-estradiol-induced
      increases in mRNA expression. These results indicate that genistein selectively
      alters expression of ARG mRNAs in LNCaP cells through modulation of both androgen
      and estrogen-induced signaling pathways.

PMID- 16299814
TI  - Post stroke urinary loss, incontinence and life satisfaction: when does post
      stroke urinary loss become incontinence?
AB  - AIMS: While urinary incontinence (UI) has been extensively studied after stroke,
      the threshold for when it becomes a social problem by affecting life satisfaction
      or social participation has not been established. The study goal was to establish
      this threshold, examine the impact of UI on life satisfaction and participation,
      and determine whether UI contributes independently to poor stroke outcome.
      METHODS: Retrospective analysis was performed on prospectively collected data
      from a cohort of consecutive admissions to the acute Neurology Stroke Service of
      a large metropolitan teaching hospital. Four hundred and sixty patients with
      ischemic stroke were prospectively evaluated for stroke severity, medical, and
      demographic factors. Telephone interviews were completed with 361 community
      dwelling subjects 6 months after stroke onset. RESULTS: The FIM bladder item was
      used to determine the frequency of urinary loss. All patients were continent
      before stroke onset, 16% reported UL at 6-month follow-up. ROC analysis suggested
      that UI once per month or more is associated with diminished quality of life and
      activity participation. Logistic regression found poor life satisfaction
      associated with ADL impairment, cognitive disability, low SF12 physical and
      mental health scores, and incontinence. Poor outcome was independent of stroke
      severity. CONCLUSIONS: Urinary loss became incontinence when it occurred at least
      monthly. UI was associated with greater dependence in basic and instrumental ADL,
      decreased participation and low life satisfaction.

PMID- 16299815
TI  - Reliability of pelvic floor muscle strength assessment using different test
      positions and tools.
AB  - AIMS: The aims of this study were to determine the intra-therapist reliability
      for digital muscle testing and vaginal manometry on maximum voluntary contraction
      strength and endurance. In addition, we assessed how reliability varied with
      different tools and different testing positions. METHODS: Subjects included 20
      female physiotherapists. The modified Oxford scale was used for the digital
      muscle testing, and the Peritron perineometer was used for the vaginal resting
      pressure and vaginal squeeze pressure assessments. Strength and endurance testing
      were performed. The highest of the maximum voluntary contraction scores was used
      in strength analysis, and a fatigue index value was calculated from the endurance
      repetitions. Bent-knee lying, supine, sitting, and standing positions were used.
      The time interval for between-session reliability was 2-6 weeks. RESULTS: Kappa
      values for the between-session reliability of digital muscle testing were 0.69,
      0.69, 0.86, and 0.79 for the four test positions, respectively. Intra-class
      correlation coefficient (ICC) values for squeeze pressure readings for the four
      positions were 0.95, 0.91, 0.96, and 0.92 for maximum voluntary contraction, and
      0.05, 0.42, 0.13, and 0.35 for endurance testing. ICC values for resting pressure
      were 0.74, 0.77, 0.47, and 0.29. CONCLUSIONS: Reliability of digital muscle
      testing was very good in sitting and good in the other three positions. vaginal
      resting pressure demonstrated very good reliability in all four positions for
      maximum voluntary contraction, but was unreliable for endurance testing. Vaginal
      resting pressure was not reliable in upright positions. Both measurement tools
      are reliable in certain positions, with manometry demonstrating higher
      reliability coefficients.

PMID- 16299816
TI  - Pharmacokinetics of a novel histone deacetylase inhibitor, apicidin, in rats.
AB  - This study is the first report of the pharmacokinetics of a novel histone
      deacetylase inhibitor, apicidin, in rats after i.v. and oral administration.
      Apicidin was injected intravenously at doses of 0.5, 1.0, 2.0 and 4.0 mg/kg. The
      terminal elimination half-life (t1/2), systemic clearance (Cl) and steady-state
      volume of distribution (Vss) remained unaltered as a function of dose, with
      values in the range 0.8-1.1 h, 59.6-68.0 ml/min/kg and 2.4-2.7 l/kg,
      respectively. Whereas, the initial serum concentration (C0) and AUC increased
      linearly as the dose was increased. Taken together, the pharmacokinetics of
      apicidin were linear over the i.v. dose range studied. The extent of urinary and
      biliary excretion of apicidin was minimal (0.017%-0.020% and 0.049% +/- 0.016%,
      respectively). Oral pharmacokinetic studies were conducted in fasting and non
      fasting groups of rats at a dose of 10 mg/kg. The Tmax, Cl/F and Vz/F were in the
      range 0.9-1.1 h, 520.3-621.2 ml/min/kg and 67.6-84.4 l/kg, respectively. No
      significant difference was observed in the oral absorption profiles between the
      two groups of rats. Apicidin was poorly absorbed, with the absolute oral
      bioavailability of 19.3% and 14.2% in fasting and non-fasting rats.

PMID- 16299817
TI  - Saline contrast sonohysterography and directed extraction, resection and biopsy
      of intrauterine pathology using a Uterine Explora Curette.
AB  - OBJECTIVE: To assess the utility of an endometrial sampling device, the Uterine
      Explora Curette, with concomitant saline contrast sonohysterography (SCSH) for
      ultrasound-directed extraction, resection and biopsy of endometrial pathology.
      METHODS: Use of the Uterine Explora Curette was prospectively evaluated in 20
      women with either infertility (n = 14), recurrent miscarriage (n = 2) or peri
      /postmenopausal bleeding (n = 4). Findings on SCSH were compared with those on
      pathological analysis. RESULTS: In all 20 cases the Uterine Explora Curette was
      used successfully during SCSH to treat endometrial filling defects. The procedure
      was well tolerated, with an average time from start to finish of 10 (range, 2-23)
      min. It was without complications, and appeared to remove or biopsy adequately
      endometrial filling defects in most patients, obviating the need for
      hysteroscopy. CONCLUSIONS: In properly selected patients, directed extraction,
      resection and biopsy using the Uterine Explora Curette during SCSH appears to be
      an effective and easy method for treating intrauterine pathology and provides a
      cost-effective alternative to operative hysteroscopy.

PMID- 16299818
TI  - Hole-doped single-walled carbon nanotubes: ornamenting with gold nanoparticles in
      water.

PMID- 16299819
TI  - Highly enantioselective synthesis of gamma-hydroxy-alpha,beta-acetylenic esters
      by asymmetric alkyne addition to aldehydes.

PMID- 16299820
TI  - Molecular encoding at the nanoscale: from complex cubes to bimetallic oxides.

PMID- 16299821
TI  - Exceptional molecular hyperpolarizabilities in twisted pi-electron system
      chromophores.

PMID- 16299822
TI  - Site-selective photocleavage of proteins by uranyl ions.

PMID- 16299823
TI  - High-yield generation of a long-lived charge-separated state in diphenylacetylene
      modified DNA.

PMID- 16299824
TI  - Simple and quantitative mechanochemical preparation of a porous crystalline
      material based on a 1D coordination network for uptake of small molecules.

PMID- 16299825
TI  - Synthesis and characterization of palladium and platinum iminoboryl complexes.

PMID- 16299826
TI  - Inverting the charges of natural nucleobase quartets: a planar platinum-purine
      quartet with pronounced sulfate affinity.

PMID- 16299827
TI  - Stabilization of the DNA I-motif structure by incorporation of 3'-S
      phosphorothiolate linkages.

PMID- 16299828
TI  - Pharmacokinetics of lactone, carboxylate and total 9-nitrocamptothecin with
      different doses and administration routes in rats.
AB  - 9-Nitrocamptothecin (9-NC) is a newly developed poorly soluble derivative of
      camptothecin and has a wide spectrum of anticancer activity in preclinical
      evaluation. The effects of the dose and administration route on pharmacokinetics
      and lactone/carboxylate equilibrium of 9-NC were studied in rats. A single
      intravenous dose of 1.5, 3 or 6 mg/kg of 9-NC solution was given to male rats (n
      = 6 per dose level). In another study, a single dose of 6 mg/kg 9-NC solution was
      given orally to rats (n = 6). Plasma samples were drawn at predetermined
      intervals and the concentrations of lactone, carboxylate and total 9-NC were
      determined by a validated HPLC method. Pharmacokinetic analysis was performed
      using non-compartmental analysis. Analysis of variance showed that the
      pharmacokinetic characteristics of lactone, carboxylate and total 9-NC were all
      independent of dose (p > 0.05). Based on the AUC measurements, the lactone 9-NC
      constituted 52% +/- 4%, 49% +/- 6% and 55% +/- 6% of the circulating total 9-NC
      in rats after intravenous administration of 1.5, 3, 6 mg/kg 9-NC solution,
      respectively. After oral administration of 6 mg/kg, the pharmacokinetics
      parameters were significantly different from those of intravenous administration
      at the same dose (p < 0.05). The lactone ratio was 60% +/- 14%. The absolute
      bioavailability of lactone and total 9-NC were calculated to be 23.4% and 22.7%,
      respectively. In conclusion, the pharmacokinetics of lactone, carboxylate and
      total 9-NC are not dose-dependent. Lactone, carboxylate and total 9-NC are poorly
      absorbed following oral administration. Both the dose and the route of
      administration have little effect on the lactone/carboxylate equilibrium of 9-NC
      in rats in vivo. But the route of administration plays an important part on the
      pharmacokinetics of 9-NC.

PMID- 16299829
TI  - Pharmacokinetic interaction of nelfinavir and methadone in intravenous drug
      users.
AB  - The effect of nelfinavir 1250 mg twice daily (b.i.d.) on the pharmacokinetics of
      methadone was determined in 14 HIV-negative methadone users. DESIGN: The
      methadone dose (20-140 mg/day) was stabilized and fixed for at least 1 month
      before nelfinavir (1250 mg b.i.d. for 8 days) was added to the regimen. The
      concentrations of methadone enantiomers were measured before and during
      nelfinavir treatment, and the concentrations of nelfinavir and its active
      metabolite, AG1402, were measured during nelfinavir treatment. Adverse events and
      withdrawal/intoxication symptoms were monitored throughout the study. RESULTS:
      Nelfinavir reduced the area under the concentration-time curve of R-methadone,
      and S-methadone by 43% and 51%, respectively. Nelfinavir and AG1402
      concentrations were within the normal range of historical data, and no subject
      experienced withdrawal symptoms during the study or required dose adjustment
      during or after the study. CONCLUSIONS: Although nelfinavir reduced the plasma
      concentrations of both R- and S-methadone, it seems to have no impact on the
      maintenance dose of methadone. A routine reduction of methadone dose is not
      recommended when coadministered with nelfinavir.

PMID- 16299830
TI  - Prenatal diagnosis of cyclopia and proboscis in a fetus with normal chromosome at
      13 weeks of gestation by three-dimensional transabdominal sonography.

PMID- 16299831
TI  - Sonographic diagnosis of fetal adrenal hyperplasia: utility for prenatal
      corticotherapy.

PMID- 16299832
TI  - Y chromosome heterochromatin variation detected at prenatal diagnosis.

PMID- 16299833
TI  - Three-dimensional ultrasound of dicephalus conjoined twins at 9 weeks of
      gestation.

PMID- 16299836
TI  - Reducing arsenic exposure from pressure-treated wood playground equipment.

PMID- 16299834
TI  - Stable and efficient intraocular gene transfer using pseudotyped EIAV lentiviral
      vectors.
AB  - BACKGROUND: We have developed minimal non-primate lentiviral vectors based on the
      equine infectious anaemia virus (EIAV). We evaluated the in vivo expression
      profiles of these vectors delivered regionally to ocular tissues to define their
      potential utility in ocular gene therapy. METHODS: EIAV vectors pseudotyped with
      VSV-G or rabies-G envelope proteins were delivered subretinally, intravitreally
      or into the anterior chambers (intracameral administration) in mice. Reporter
      gene (eGFP) expression was analysed using in vivo retinal imaging or histological
      examination of eyes and brains at intervals between 3 days and 16 months. We
      investigated the effects of vector titre, pseudotype, genome configuration, site
      of intraocular administration, intentional retinal trauma and the degree of
      retinal maturation on the spatial and temporal expression profiles of these
      vectors. RESULTS: Subretinal vector delivery resulted in efficient and stable
      transduction of retinal pigment epithelial (RPE) cells and variable transduction
      of photoreceptors up to 16 months post-injection. Retinal trauma facilitated the
      local transduction of neurosensory retinal cells. Intracameral administration of
      VSV-G- but not rabies-G-pseudotyped vectors produced stable eGFP expression in
      corneal endothelial cells and trabecular meshwork. CONCLUSIONS: The cellular
      tropism and expression kinetics of optimised EIAV vectors after intraocular
      administration make them attractive vehicles for delivering therapeutic genes in
      the management of inherited and acquired retinal and anterior segment disorders.

PMID- 16299835
TI  - Over-the-counter medication use by pregnant women.

PMID- 16299837
TI  - I recently had mitral valve repair surgery. Now I notice that I'm having trouble
      catching my breath. Is this a normal side effect of this type of heart surgery?

PMID- 16299839
TI  - Joint infections. Early aggressive treatment is vital.

PMID- 16299838
TI  - Rethinking early bone-loss treatment.

PMID- 16299840
TI  - Please explain the difference between seborrhea and psoriasis.

PMID- 16299841
TI  - I am on medication for high blood pressure, and recently bought a home blood
      pressure monitoring device. I have found that my blood pressure varies at
      different times of the day. Is this normal?

PMID- 16299842
TI  - My doctor told me that my aortic valve is closing up. He said that it will
      probably need to be replaced in the future if it keeps getting worse. What can I
      do to stop this from progressing?

PMID- 16299843
TI  - To keep blood pressure down, go easy on painkillers.

PMID- 16299844
TI  - Use leisure-time activities to guard against strokes.

PMID- 16299845
TI  - Since I started taking clopidogrel (Plavix), I've noticed small bruise marks on
      my body. My doctor says that I should continue taking it. Is that good advice?

PMID- 16299846
TI  - I recently underwent a successful cardioversion to correct a rapid pulse (140
      beats per minute) attributed to atrial fibrillation. My cardiologist then
      prescribed 400 milligrams a day of amiodarone for two weeks, then 200 milligrams
      a day. What do you think of this drug?

PMID- 16299847
TI  - One pill, two conditions.

PMID- 16299849
TI  - Activists scramble to clarify terms of new Medicare law.

PMID- 16299848
TI  - Pre-diabetes could be hurting your heart.

PMID- 16299850
TI  - Sentencing rejects HIV-positive man's claim of ineffective counsel.

PMID- 16299851
TI  - Lambda Legal praises new California transplant law.

PMID- 16299852
TI  - Sentencing. HIV not a mitigating factor in manslaughter case.

PMID- 16299854
TI  - Discrimination. Disabled man tries to avoid suit.

PMID- 16299853
TI  - ACLU files injunction over youth harassment in Hawaii facility.

PMID- 16299855
TI  - Cystatin C: new measure for predicting cardiac death.

PMID- 16299856
TI  - Pomegranates may combat prostate cancer.

PMID- 16299857
TI  - Alzheimer's vaccine reduces plaque.

PMID- 16299860
TI  - Are veggies the new statin?

PMID- 16299859
TI  - Plastic - lupus link.

PMID- 16299858
TI  - New role for Herceptin in treating bladder cancer.

PMID- 16299861
TI  - I'm 72, have early prostate cancer, and my doctor recommended "watchful waiting".
      What does that mean and why would I do this instead of removing the cancer?

PMID- 16299862
TI  - What can be done about bone loss and what are the current treatments for it?

PMID- 16299863
TI  - Can medication be taken after the expiration date?

PMID- 16299864
TI  - Reading the signs of starvation.
AB  - Guidelines for managing malnutrition in adolescent eating disorders are based on
      limited evidence. Swenne and Engstrom's study explored the relationship between
      symptoms, signs and weight status in this patient group, towards refining
      clinical approaches to nutritional assessment in adolescents. CONCLUSION: The
      need to compare findings across studies is crucial for research in nutritional
      assessment of adolescents

PMID- 16299865
TI  - Can cry in the newborn be used as an assessment of pain?
AB  - Pain in the neonate is a complex subject. The assessment of pain should be simple
      and clinically usable. So far, the scales that have been used to assess pain are
      too time consuming and complex. The analysis of cry in a simple manner, as
      described in this issue of Acta Paediatrica by Bellieni et al., could be used in
      a simple and effective way at the bedside. CONCLUSION: Since sick and premature
      newborns are not studied, the scale needs further confirmation.

PMID- 16299866
TI  - The effect of nebulized budesonide treatment in children with mild to moderate
      exacerbations of asthma.
AB  - BACKGROUND: The role of inhaled corticosteroids in the treatment of acute asthma
      remains a controversial subject. OBJECTIVE AND METHODS: A randomized, double
      blind, placebo-controlled parallel-group clinical trial on the effect of a 5-d
      course of nebulized budesonide treatment in children with mild to moderate
      exacerbation of asthma was performed. The need for systemic corticosteroid
      intervention was evaluated as the primary outcome measure. RESULTS: Sixty-seven
      children aged 6 to 15 y were enrolled. During the emergency department phase,
      they received three nebulizations of either budesonide(1 mg/dose) or placebo, and
      then in the home phase of the study, they continued their study medications twice
      a day for another 4 d. Though the level of improvement in the emergency
      department phase was similar between the groups given either budesonide or
      placebo treatments (6.8 +/-1.9% vs 4.0+/-1.5%, p = 0.30, respectively), nebulized
      budesonide caused a trend towards a benefit in terms of the need for systemic
      corticosteroid intervention (2/33 vs 7/34, p = 0.07), but not in secondary
      outcome measures. CONCLUSION: Though we show a tendency towards a benefit with
      nebulized budesonide in children with mild to moderate exacerbations in terms of
      prevention of progression of the illness, the documented benefit is small and
      includes, at least, consideration for clinical significance, cost-effectiveness,
      impracticality and safety.

PMID- 16299867
TI  - Significant improvement of eczema with skin care and food elimination in small
      children.
AB  - AIM: To evaluate common methods of investigation and treatment in children
      younger than 2 y of age with eczema, with or without sensitization to food
      allergens. METHODS: One hundred and twenty-three children younger than 2 y of age
      with eczema and suspected food allergy were included in this prospective study.
      The children underwent skin-prick test with cow's milk, fresh hen's egg white and
      wheat. Specific IgE to milk and egg white was analysed. The eczema extent and
      severity was estimated with SCORAD before and after treatment. Children with a
      positive skin-prick test were instructed to exclude that food item from their
      diet. All children were treated with emollients and topical steroids when needed.
      RESULTS: Sixty-two of the children were skin-prick positive to at least one of
      the allergens; 62% had mild, 30% moderate and 8% severe eczema at their first
      visit. After treatment, 90% had mild, 10% moderate and 0% severe eczema. Forty
      six per cent of the children had circulating IgE antibodies to milk or egg white.
      Ten per cent had specific IgE but negative skin-prick test to the same allergen.
      This subgroup improved their eczema significantly without elimination diet.
      CONCLUSION: The conventional treatments for children with eczema, i.e. skin care
      and food elimination, are effective. The beneficial effect of skin care as the
      first step should not be neglected, and it may not be necessary to eliminate food
      allergens to relieve skin symptoms in all food-sensitized children with eczema.

PMID- 16299868
TI  - Normal physical working capacity in prepubertal children with type 1 diabetes
      compared with healthy controls.
AB  - BACKGROUND: Exercise testing has become a valuable help for the physician to
      examine the influence of recommended exercise training on physical fitness.
      However, the question as to how diabetic prepubertal children differ from their
      non-diabetic peers in their performance capacity has only partial and sometimes
      conflicting answers in the literature. AIM AND METHODS: The aim of the current
      study was thus to evaluate aerobic fitness during an incremental submaximal test
      (measure of the Physical Working Capacity 170 (PWC170)) in 17 well-controlled
      prepubertal insulin-dependent diabetic boys aged 8.5-13 y. Eighteen healthy
      prepubertal boys matched for age, body size and physical activity served as
      controls. Part of the method was to check capillary blood glucose level in the
      diabetic patients and in nine of the healthy subjects throughout the exercise.
      RESULTS: From this experiment it appeared that the level of physical fitness was
      similar in diabetic and healthy boys (PWC170 2.28+/-0.09 vs 2.37+/-0.13 W x kg(
      1)). While glucose homeostasis was well maintained in the healthy group, diabetic
      children showed a marked fall in blood glucose during the exercise. In addition,
      the PWC170 level correlated significantly with the estimate of energy expenditure
      attributed to vigorous activities in the diabetic boys. CONCLUSION: By studying
      the responses to incremental exercise there is growing evidence that normal
      physical fitness is preserved in diabetic prepubertal boys given appropriate
      involvement in physical activity.

PMID- 16299869
TI  - Persistent effects of a pedagogical device targeted at prevention of severe
      hypoglycaemia: a randomized, controlled study.
AB  - AIM: To study the long-term use of self-study material in type 1 diabetes patient
      education targeted at the prevention of severe hypoglycaemia. METHODS: Randomized
      1:1:1 control study in three local hospitals. We studied 332 type 1 diabetes
      patients from the geographic population, aged 2.6-18.9 y at entry. The
      intervention group received a videotape and brochure in which interviewed
      patients, parents and medical experts reviewed in detail practical skills for
      self-control and treatment, with the aim of preventing severe hypoglycaemia.
      There were two control groups: one received a videotape and brochure with general
      diabetes information and the other only traditional treatment. Primary endpoints
      were severe hypoglycaemia needing assistance by another person and HbA1c.
      Dissemination, reading/viewing level, patients' attitudes and extra contact with
      caregivers were also investigated. At 24 mo, 249 subjects provided data. RESULTS:
      The yearly incidence of severe hypoglycaemia decreased at 24 mo from 42% to 25%
      (difference 17%, 95% CI 3-31, p = 0.0241) in the intervention group, but not in
      controls. HbA1c remained unchanged. Video use during months 13-24 was higher in
      the intervention group than in controls (p = 0.0477), ranging from 1-15 (median
      2) times, among 37% of patients (months 1-12, 100%). Higher future use was
      anticipated for intervention material (p = 0.0003). Extra caregiver contact was
      related to severe hypoglycaemia (p = 0.0009). The cost of the material was <EUR
      10 per patient. CONCLUSION: Mass-distributed pedagogical devices such as high
      quality video programmes and brochures may reach high dissemination levels and,
      when targeted, contribute to the prevention of severe hypoglycaemia over a longer
      period of time, being a cost-effective complement to traditional care.

PMID- 16299870
TI  - Suggesting reviewers affects outcome?

PMID- 16299871
TI  - Growth hormone treatment in 35 prepubertal children with achondroplasia: a five
      year dose-response trial.
AB  - BACKGROUND: Achondroplasia is a skeletal dysplasia with extreme,
      disproportionate, short stature. AIM: In a 5-y growth hormone (GH) treatment
      study including 1 y without treatment, we investigated growth and body proportion
      response in 35 children with achondroplasia. METHODS: Patients were randomized to
      either 0.1 IU/kg (n = 18) or 0.2 IU/kg (n = 17) per day. GH treatment was
      interrupted for 12 mo after 2 y of treatment in prepubertal patients to study
      catch-down growth. Mean height SDS (HSDS) at start was -5.6 and -5.2 for the low-
      and high-dose groups, respectively, and mean age 7.3 and 6.6 y. RESULTS: Mean
      growth velocity (baseline 4.5/4.6 cm/y for the groups) increased significantly by
      1.9/3.6 cm/y during the first year and by 0.5/1.5 cm/y during the second year.
      During the third year, a decrease of growth velocity was observed at 1.9/1.3 cm/y
      below baseline values. HSDS increased significantly by 0.6/0.8 during the first
      year of treatment and in total by 1.3/1.6 during the 5 y of study. Sitting height
      SDS improved significantly from -2.1/-1.7 to -0.8/0.2 during the study. Body
      proportion (sitting height/total height) or arm span did not show any significant
      change. CONCLUSION: GH treatment of children with achondroplasia improves height
      during 4 y of therapy without adverse effect on trunk-leg disproportion. The
      short-term effect is comparable to that reported in Turner and Noonan syndrome
      and in idiopathic short stature.

PMID- 16299872
TI  - Normal spontaneous cortisol secretion in children after autologous bone marrow
      transplantation.
AB  - AIM: To describe spontaneous cortisol secretion in children after autologous bone
      marrow transplantation (BMT) for acute leukaemia and lymphoma. METHODS:
      Spontaneous cortisol secretion was analysed in 39 children before and after BMT.
      Thirteen patients were conditioned with chemotherapy only (group 1), and 26
      patients also with total body irradiation (TBI). In the TBI group, 14 patients
      had received no additional irradiation (group 2), whereas 12 patients had
      received cranial irradiation (CRT) previously (group 3). RESULTS: Before BMT, in
      comparison with group 1, mean morning cortisol was significantly lower in group 2
      (252 vs 415 mmol/l, p = 0.004), but not in group 3 (vs 312 mmol/l, p = 0.12).
      There was no change in group 1 six months after BMT (to 379 nmol/l), whereas
      morning cortisol increased significantly in group 2 and group 3 (to 386 and 343
      nmol/l, respectively; p < 0.05). The change in mean morning cortisol correlated
      negatively with pretransplant morning cortisol (r = -0.63, p < 0.001). Neither
      TBI nor CRT were associated with changes in morning cortisol. CONCLUSION:
      Spontaneous cortisol secretion is maintained after BMT irrespective of whether
      cranial or total body irradiation has been given or not.

PMID- 16299873
TI  - Bone age and probable aetiological causes in primary nocturnal enuresis.
AB  - AIM: To investigate probable aetiological risk factors and to identify whether
      there are any differences in bone age between normal children and children with
      primary nocturnal enuresis (PNE). METHODS: Ninety children with primary nocturnal
      enuresis and 40 healthy children were included in the study. Enrolment began in
      January 2001, and continued through July 2002. Data were obtained via
      consultation with children and their families, physical examination and
      laboratory findings. Left hand and wrist graphs of each patient were acquired,
      and, using Tanner Whitehouse charts (TW-2), bone ages were determined via
      comparison of 20 hand and wrist bones. RESULTS: Of the total of 90 children with
      primary nocturnal enuresis participating in the study, 52 (57.8%) were male and
      38 (42.2%) were female. Of the control group, 24 (60%) were male and 16 (40%)
      were female. Differences between chronological ages and bone ages of the PNE and
      control groups were 0.57+/-0.59 and 0.54+/-0.67 y, respectively, and no
      significant difference was seen (p = 0.484). In 90% of the children in the PNE
      group there was found to be a primary nocturnal enuresis history in the family,
      whereas in the control group this rate was only 7.5%. Of the children with PNE,
      62.2% had very deep sleeping habits, while 7.5% of the control group had this
      problem. CONCLUSION: Our study provides no evidence that bone ages of children
      suffering from PNE are lower than normal children. We found that a family history
      of enuresis, male sex and difficulty in waking were risk factors in primary
      nocturnal enuresis.

PMID- 16299874
TI  - Cognitive and behavioural characteristics in blind children with bilateral optic
      nerve hypoplasia.
AB  - AIM: To describe cognitive and behavioural characteristics in a group of blind
      children with bilateral optic nerve hypoplasia (ONH). METHODS: Data from records,
      parents, teachers, and repeated developmental assessments of 13 blind children
      with ONH born in 1988-1998 were analysed. All children had neuroimaging and/or
      hormonal evidence of midline malformations. They were all blind and able to
      communicate with speech. RESULTS: Severe mood swings and temper tantrums were
      common, especially during the first years of life. Later in life, sluggish tempo,
      low frustration tolerance and a narrow range of interests were common. Autism had
      been diagnosed in 6/13 children, autistic-like condition (ALC) was found in
      another three. The behaviour of the remaining four children was not within the
      autism spectrum. Eight children had cognitive capacities within the normal or
      near-normal range; five had mental retardation. Autism/ALC was found in all
      cognitive subgroups. All children exhibited fluent speech and, of these, 12 had
      started to talk at the expected age, but had clear deficiencies in communicative
      ability. CONCLUSION: These children had a common pattern of behavioural
      characteristics including autism spectrum disorders independent of intellectual
      capacities.

PMID- 16299875
TI  - Blood glucose testing at alternate sites in newborn infants.
AB  - AIM: To compare a method of testing at alternate skin sites (AST) with that of
      the usual heel-stick approach (SM) for determining blood glucose levels in
      newborn infants. Our other aims were to compare these methods as regards their
      accuracy, the pain caused by the procedures, the times taken to obtain a result
      and the possible delay in accurate test results using AST during rapid changes in
      blood glucose. METHODS: One hundred and eighty-six preterm and term infants were
      enrolled. The blood glucose levels were determined by a standard bedside method
      (SM, HemoCue) and AST (Freestyle), which permitted blood samples to be taken from
      the arm or leg. RESULTS: The levels of blood glucose ranged between 0.6 and 8.6
      mmol/l. We found a significant correlation between SM and AST (r = 0.90, p <
      0.001). The coefficient of variation was similar, pain was significantly less
      (median pain score 3.5 vs 7.5, p < 0.01) and the time taken to obtain a result
      significantly shorter (mean 35 vs 111 s, p < 0.01) with AST than with SM. No
      significant differences were found between these methods during rapid changes in
      the blood glucose levels. CONCLUSION: AST, a relatively simple and painless
      method of determining blood glucose levels in newborn infants, is acceptably
      accurate and causes minimal blood loss.

PMID- 16299876
TI  - Development and validation of the ABC pain scale for healthy full-term babies.
AB  - AIM: We developed and validated a pain scale (ABC scale) for term babies based on
      acoustic features of crying. METHODS: The scale consisted of three different cry
      parameters: (a) pitch of the first cry; (b) rhythmicity of the crying bout; (c)
      constancy of crying intensity. These parameters were previously found to
      distinguish between medium and high levels of pain measured by spectral analysis
      of crying. We validated the scale using healthy term babies undergoing routine
      heel prick. Concurrent validity was assessed comparing pain values obtained with
      our scale with those obtained with another pain scale; this relationship was also
      used to assess the sensitivity of the scale. To assess specificity we compared
      the ABC scores during a painful event (heel prick) with two non-painful events
      (preliminary phase of prick in the same group of babies, and heel prick with
      analgesia in another group). RESULTS: Specificity: (a) analgesic/non-analgesic
      comparison, p < 0.0001; (b) pain/sham comparison, p < 0.0001). Sensitivity: a
      high correlation between scores of the ABC scale and the Douleur Aigue du Nouveau
      Ne scale indicates good sensitivity. Concurrent validity: Spearman rho = 0.91.
      Internal consistency: Cronbach's alpha = 0.76. Inter-rater reliability: Cohen's
      kappa for multiple raters = 0.83. Intra-rater reliability: Cohen's kappa = 0.85.
      Practicality: All nurses who used it scored the scale as "good". CONCLUSION: The
      ABC scale proved to be simple and reliable for assessing pain in healthy, non
      intubated term newborns.

PMID- 16299877
TI  - Sonographic detection of the optic radiation.
AB  - OBJECTIVE: To describe a region of hyperechoic white matter adjacent to the
      atrium of the lateral ventricle of preterms, and to speculate on the relevance of
      detecting preterm white matter injury. PATIENTS AND METHODS: Cranial ultrasound
      images of 92 preterms of gestational age (GA) 32 wk or less were reviewed. For
      each infant, one first week standard coronal image was used for measurement of
      grey values around the para-atrial region of interest (PAROI) relative to the
      choroid plexus. For verification of the sonographic anatomy, MR images of an
      adult brain were used. For reference, neuro-anatomical images were compared in
      several atlases. In a group of nine preterms of similar GA with cystic
      periventricular leukomalacia (PVL) or MR-confirmed white matter disease, the
      disappearance of the PAROI was examined. RESULTS: The hyperechoic para-atrial
      area, subjectively detected in 84% of the patients, was situated bilaterally
      between the inner end of the lateral fissure and the upper third of the choroid
      plexus. In white matter caudal to the atrium, the hyperechoic band could be
      pursued towards the calcarine area. The average ratio of grey value around the
      PAROI to the choroid plexus was 0.787 (SD = 0.072, median 0.791). There was no
      correlation between PAROI grey value and gestational age. At 26 wk gestational
      age, the average ratio was 0.781 (n = 14), and 0.789 (n = 17) at 31 wk. Location
      of the PAROI agrees with the angle of the upper loop of the optic radiation. None
      of the nine infants with white matter damage had PAROIs clearly distinguishable
      from flaring. CONCLUSION: The symmetrical and unchanged acoustic character
      between 26 and 31 wk of gestational age argues in favour of the hypothesis that
      the PAROI is an anatomical structure. The localization of the hyperechoic band
      supports the hypothesis that it represents part of the optic radiation. Further
      study is needed to examine the absence of a hyperechoic para-atrial band as a
      prognostic marker of the extension and severity of white matter injury.

PMID- 16299878
TI  - The impact of newborn bathing on the prevalence of neonatal hypothermia in
      Uganda: a randomized, controlled trial.
AB  - AIM: To elucidate the impact of bathing on the prevalence of hypothermia among
      newborn babies exposed to the skin-to-skin (STS) care technique before and after
      bathing. METHODS: Non-asphyxiated newborns after vaginal delivery (n = 249) in a
      Ugandan referral hospital were consecutively enrolled and randomized either to
      bathing at 60 min postpartum (n = 126) or no bathing (n = 123). All mothers
      practised skin-to-skin care of their newborns. Four rectal and tympanic
      registrations of newborn temperatures were carried out in both groups directly
      after drying at birth, and at 60, 70 and 90 min postpartum. RESULTS: Bathing of
      newborns in the first hour after delivery resulted in a significantly increased
      prevalence of hypothermia, defined as temperature <36.5 degrees C, at 70 and at
      90 min postpartum despite the use of warmed water and the application of the STS
      method. There was no neonatal mortality. Aside from the bathing procedure, no
      background factor potentially predisposing the newborns to hypothermia was
      identified. CONCLUSION: Bathing newborn babies shortly after birth increased the
      risk of hypothermia despite the use of warm water and STS care for thermal
      protection of the newborn.

PMID- 16299879
TI  - Meconium aspiration induces neuronal injury in piglets.
AB  - AIM: Meconium aspiration-induced hypertensive lung injury, especially when
      connected with perinatal asphyxia, has been associated with brain damage. We
      aimed to determine the neuronal injury induced by pulmonary meconium
      contamination alone and with concurrent asphyxia. METHODS: 36 anaesthetized and
      ventilated newborn piglets were haemodynamically monitored for 6 h. Seven piglets
      without concurrent asphyxia and seven piglets with asphyxia were instilled with a
      bolus of human meconium intratracheally. Seven piglets had only asphyxia and 15
      piglets served as controls. The brains were studied histologically. RESULTS:
      Meconium aspiration did not change systemic haemodynamics acutely, while its
      combination with asphyxia diminished the abrupt postasphyxic systemic
      hypertensive peak and resulted in a transient increase in carotid artery flow,
      not seen after isolated asphyxia. Systemic pressure declined after 4 h in all
      insulted groups, but only isolated asphyxia was associated with a sustained
      decrease in carotid artery flow. Arterial oxygenation remained normal, except
      during the acute insults. Brain examination after meconium instillation indicated
      neuronal injury, especially in the CA3 region of the hippocampus. Asphyxia
      resulted in neuronal injury in the cortical, cerebellar and hippocampal hilus
      regions. CONCLUSION: Severe meconium aspiration itself may result in hippocampal
      neuronal injury.

PMID- 16299880
TI  - Associations between voluntary and involuntary forms of perinatal loss and child
      maltreatment among low-income mothers.
AB  - AIM: This study explored maternal history of perinatal loss relative to risk of
      child physical abuse and neglect. METHODS: The 518 study participants included
      118 abusive mothers, 119 neglecting mothers, and 281 mothers with no known
      history of child maltreatment. Interviews and observations were conducted in the
      participants' homes, and comparisons were made between women without a history of
      perinatal loss and women with one and multiple losses relative to risk for child
      maltreatment. RESULTS: Compared to women with no history of perinatal loss, those
      with one loss (voluntary or involuntary) had a 99% higher risk for child physical
      abuse, and women with multiple losses were 189% more likely to physically abuse
      their children. Compared to women with no history of induced abortion, those with
      one prior abortion had a 144% higher risk for child physical abuse. Finally,
      maternal history of multiple miscarriages and/or stillbirths compared to no
      history was associated with a 1237% increased risk of physical abuse and a 605%
      increased risk of neglect. CONCLUSION: Perinatal loss may be a marker for
      elevated risk of child physical abuse, and this information is potentially useful
      to child maltreatment prevention and intervention efforts.

PMID- 16299881
TI  - [A patient with pulmonary metastasis of phyllodes tumour of the breast].
AB  - BACKGROUND: Phyllodes tumours are rare neoplasms of the female breast. Tumours
      range from the benign to the highly malignant. Based on histological growth
      pattern, number of mitoses, pleomorphism and stroma characteristics, tumours are
      classified as malignant, borderline, or benign. After surgical treatment of
      malignant phyllodes tumours, ten-year survival of 42% is reported. Metastatic
      tumours have a poor prognosis with no long-term survival. MATERIAL AND METHODS:
      We present the case history of a 59-year-old woman with a pulmonary metastasis
      from a malignant phyllodes tumour of the breast. RESULTS: The patient presented
      with a rapidly growing tumour of the right lung. Because of suspected malignancy,
      bilobectomy of the right lung was performed. Microscopic examination of the
      resected specimen showed a metastasis from a malignant sarcomatous tumour. Review
      of the specimen from a mastectomy 14 months earlier, for what was then considered
      a benign phyllodes tumour, confirmed a diagnosis of a primary malignant phyllodes
      tumour with pulmonary metastases. INTERPRETATION: Diagnosis and treatment of
      phyllodes tumours require close cooperation between the radiologist, the
      pathologist and the clinician.

PMID- 16299882
TI  - Psychoactive drug prescribing by Dutch child and adolescent psychiatrists.
AB  - AIM: To gain more insight into the prescribing of psychoactive drugs by Dutch
      child psychiatrists. METHODS: A questionnaire was sent to all child psychiatrists
      in the Netherlands. Questions were asked about the prescribing of
      antidepressants, antipsychotics, anxiolytics and psychostimulants for psychiatric
      disorders in children. RESULTS: The preference of specific antidepressants,
      antipsychotics and anxiolytics depends on the disorder. For different disorders,
      off-label prescribing varies from 19 to 71%. CONCLUSION: Preferences differ
      widely. Off-label drug prescribing is high. More studies on the efficacy and
      safety of psychoactive drugs in children are therefore required.

PMID- 16299883
TI  - [Investigation in suspected pulmonary tumor].

PMID- 16299884
TI  - Neighbourhood social and socio-economic composition and injury risks.
AB  - AIM: To investigate whether social and socio-economic characteristics of the
      population within a parish influence childhood injury. METHODS: The study
      encompasses all children aged 0-15 y living in Stockholm County over the 3-y
      period 1999-2001 (about 360,000 children per year), grouped into parish of
      residence (138 parishes). The effect of parish attributes on injury rate were
      analysed based on three indices (deprivation, socio-economic status and social
      integration) derived by a factor analysis of 11 characteristics of the parishes'
      population, each index being split into three levels. Childhood injury resulting
      in at least one night of hospitalization during the period 1999-2001 was
      considered (n = 5540) by index, and rate ratios were calculated for 12 injury
      causes using parishes forming the best level of the index as the reference group.
      RESULTS: Higher levels of deprivation negatively influenced pedestrian injury
      rates, had a protective effect on other traffic-related injuries, and negatively
      affected some other types of unintentional injuries. Higher concentrations of
      people with low socio-economic status did not impact on the risk of traffic and
      fall injuries, but increased that of burns/scalds and cases of poisoning.
      Parishes with lower levels of social integration had significantly higher rates
      of bicycle- and moped-related injuries, and also of self-inflicted ones.
      CONCLUSION: Compositional characteristics of the population in a residential area
      affect injury to varying degrees and direction according to type of injury. The
      underlying mechanisms are likely to be specific to injury type.

PMID- 16299885
TI  - The complexity of the psychosocial situation in children and adolescents with
      heart disease.
AB  - AIM: To describe the psychosocial situation of children/adolescents with heart
      disease and their families, an inventory method was worked out. METHODS: Ninety
      seven children/adolescents with congenital heart disease (CHD) were graded into
      three categories with respect to complexity of CHD. Group I included 42 patients
      with malformations requiring standardized operations. Group II included 20
      patients with more complicated malformations, and group III included 35 patients
      with very complex malformations. The patients were compared with controls without
      heart disease, matched for age and gender. The psychosocial impact of CHD was
      measured by the inventory. RESULTS: The most frequent problems in the patient
      group were healthcare and treatment-related needs (71/97) in the external sphere,
      family symptoms (68/97) in the interpersonal sphere, and somatic symptoms (19/97)
      in the personal sphere. Corresponding numbers in the controls were treatment
      related needs (15/97), family (9/97) and somatic symptoms (25/97). Fifty per cent
      of the symptoms in the patient groups were mild, 30% moderate and 20% severe. The
      most severe symptoms were found in the interpersonal sphere, where family
      symptoms constituted the most severe variable. The frequency of severe problems
      in the personal sphere was 11% in the patients and 1% in the controls. This
      inventory method differentiates the grades of medical complexity both regarding
      number and severity of psychosocial symptoms. It indicates severe personal
      problems in the most complex group and shows that they have severe personal
      problems independent of family problems. CONCLUSION: This study elucidates the
      psychosocial complexity in children/adolescents with CHD, which has clinical
      implications in developing a psychosocial care programme.

PMID- 16299886
TI  - A three-year population-based study of antibiotic treatments for children.
AB  - AIM: To describe the use of systemic antibiotics in the paediatric population of
      the Emilia-Romagna region (Italy) during the period 2000-2002. METHODS: Data were
      extracted from the drug prescription database of Emilia-Romagna. RESULTS:
      Treatment rates were within the range 1016-1151 treatments per 1000 children
      years, according to the observed year. Chephalosporins were the most prescribed
      antibiotic class. CONCLUSION: The paediatric population of Emilia-Romagna is
      heavily exposed to systemic antibiotics. Further studies are needed to find out
      determinants of antibiotic overuse.

PMID- 16299887
TI  - Legionella waltersii--a novel cause of pneumonia?
AB  - A 5-y-old girl was admitted to our hospital with fever, cough, respiratory
      distress and rapidly increasing oxygen requirements. A chest radiograph showed
      bilateral central infiltrates. PCR was performed with pharyngeal washings and
      revealed Legionella DNA, while no genetic materials of other pathogens such as
      respiratory viruses, Mycoplasma and Chlamydia were detected. The clinical
      condition improved gradually after administration of steroids and therapy with
      clarithromycin. Further sequencing of Legionella DNA led to the identification of
      Legionella waltersii. This Legionella species has never been described as a human
      pathogen before. CONCLUSION: For the first time, L. waltersii was identified as a
      cause of severe pneumonia. Since L. waltersii is not detected by routine
      laboratory tests, it may be speculated that these bacteria, like other Legionella
      species, are underestimated as a probable cause of community-acquired pneumonia.

PMID- 16299888
TI  - Systemic lupus erythematosus (SLE) presenting with nephrotic syndrome and
      membranous glomerulopathy in a 10-year-old girl.
AB  - The authors report the case of a 10-y-old girl with clinical diagnosis of
      systemic lupus erythematosus (SLE), made at the age of 6 y, based upon arthritis,
      serositis, haematological disorder and positive antinuclear antibody. The first
      manifestation of disease--Raynaud's phenomenon--appeared at the age of 4 y. Seven
      months after the diagnosis, she developed nephrotic proteinuria with haematuria.
      Percutaneous renal biopsy showed membranous glomerulonephritis, the least common
      form of lupus nephritis. CONCLUSION: Intravenous cyclophosphamide therapy
      associated with oral prednisolone proved effective in inducing complete remission
      of nephrotic syndrome.

PMID- 16299889
TI  - Implantable cardioverter defibrillator (ICD) at end of life #112.

PMID- 16299890
TI  - Proceedings and abstracts from the 4th Annual Safety Pharmacology Society
      meeting, Covington, Kentucky, USA, September 27-29, 2004.

PMID- 16299891
TI  - Letter regarding article by Markus et al, "Dual antiplatelet therapy with
      clopidogrel and aspirin in symptomatic cardiac stenosis evaluated using doppler
      embolic signal detection: the Clopidogrel and Aspirin for Reduction of Emboli in
      Symptomatic Carotid Stenosis (CARESS) trial".

PMID- 16299892
TI  - [Viewpoints: The future of the Gastroenterology and Hepatology Specialty --
      Address of the President of the Austrian Gastroenterology Hepatology Society on
      the occasion of the 38th Annual Meeting].

PMID- 16299894
TI  - Psychometric validation of the obsessive belief questionnaire and interpretation
      of intrusions inventory--Part 2: Factor analyses and testing of a brief version.
AB  - The Obsessive Belief Questionnaire (OBQ) and the Interpretation of Intrusions
      Inventory (III) were designed to assess beliefs and appraisals considered
      critical to the pathogenesis of obsessions. In previous reports we have described
      the construction and psychometric properties of these measures. In this study a
      battery of questionnaires assessing anxiety, depression, and obsessive compulsive
      symptoms was completed by 410 outpatients diagnosed with obsessive compulsive
      disorder, 105 non-obsessional anxious patients, 87 non-clinical adults from the
      community, and 291 undergraduate students. Items from 6 theoretically derived
      subscales of the OBQ were submitted to factor analysis. Three factors emerged
      reflecting (1) Responsibility and threat estimation, (2) Perfectionism and
      intolerance for uncertainty, and (3) Importance and control of thoughts. A 44
      item version (OBQ-44) composed of high-loading items from the 3 factors showed
      good internal consistency and criterion-related validity in clinical and non
      clinical samples. Subscales showed less overlap than original scales. Factor
      analysis of the III yielded a single factor, suggesting the total score be used
      in lieu of the 3 rationally derived subscales. The scales performed well on tests
      of convergent validity. Discriminant validity was promising; hierarchical
      regression analyses indicated that the OBQ subscales and III generally predicted
      OC symptoms after controlling for general distress. A revision of the OBQ, the
      OBQ-44, is included in the appendix

PMID- 16299895
TI  - Factors affecting circulating mRNA for nephrin.

PMID- 16299896
TI  - Immunogenicity testing by electrochemiluminescent detection for antibodies
      directed against therapeutic human monoclonal antibodies.

PMID- 16299897
TI  - Development of a novel enzymatic cycling assay for total homocysteine.

PMID- 16299898
TI  - Automated enzymatic assay for measurement of lithium ions in human serum.

PMID- 16299899
TI  - Development of an automated enzymatic assay for the determination of glycated
      serum protein in human serum.

PMID- 16299900
TI  - Toward multianalyte immunoassays: a flow-assisted, solid-phase format with
      chemiluminescence detection.

PMID- 16299902
TI  - Lose weight to fight GERD.

PMID- 16299901
TI  - Recombinant cell-based bioluminescence assay for androgen bioactivity
      determination in clinical samples.

PMID- 16299904
TI  - Splitting the difference.

PMID- 16299903
TI  - Sustained gastric mucosal acidosis after hemorrhage in spite of rapid hemodynamic
      restoration with blood or hypertonic/hyperoncotic solution.
AB  - Splanchnic hypoperfusion has been implicated as the motor of multiple organ
      dysfunction. Hypertonic saline has shown to benefit microcirculatory blood flow.
      In hemorrhaged animals, we tested the hypothesis that small-volume 3% NaCl/10%
      dextran 40 (3%HSD) promotes global and regional improvements, including gastric
      mucosal acidosis reversal. Seventeen dogs (18.8 +/- 1.2 kg) were bled (20 mL/min)
      to a mean arterial pressure of 40-45 mm Hg, which was maintained at these levels
      for 15 min. They were randomly assigned to two groups: Blood (n = 9), total shed
      blood retransfused at 40 mL/min; or a 4-min bolus injection of 3%HSD (n = 8), in
      a volume equivalent to 25% of total shed blood. All animals were followed for 30
      min thereafter. Gastric mucosal PCO2 (gas tonometry), portal vein PCO2, superior
      mesenteric artery blood flow (SMA, ultrasonic flowprobes), and systemic and
      regional O2-derived variables were evaluated throughout the protocol. Hemorrhage
      induced significant reductions of arterial pressure, cardiac output, and SMA
      blood flow, while portal-arterial and gastric-arterial PCO2 gradients increased.
      Total shed blood transfusion, as well as 3%HSD bolus injection, promptly restored
      all parameters, except for the increased gastric-arterial PCO2 gradient. We
      conclude that persistent gastric mucosal acidosis cannot be adequately predicted
      by global and splanchnic O2 derived variables in following hemorrhage and
      resuscitation with total shed blood transfusion or small-volume hypertonic
      hyperoncotic solution.

PMID- 16299905
TI  - ACE giveaway could save lives, money.

PMID- 16299907
TI  - Checks recommended for relatives of people with idiopathic dilated
      cardiomyopathy.

PMID- 16299908
TI  - Treating depression after a heart attack.

PMID- 16299909
TI  - Ask the doctor. My doctor told me that I have "low ejection fraction," but I feel
      fine. How can this be? I thought this was part of heart failure and would make
      someone feel bad. Should I do anything about it, even though I don't have any
      symptoms?

PMID- 16299910
TI  - [Transplantation of the Pes anserinus in the patella tendon and in the internal
      patella wing].

PMID- 16299911
TI  - Setting new standards.

PMID- 16299912
TI  - Many issues in store for new FDA commissioner.

PMID- 16299913
TI  - Royal Society puts personalized medicine in perspective.

PMID- 16299914
TI  - Study shows newer schizophrenia treatments no more effective than old.

PMID- 16299915
TI  - Priority patent applications.

PMID- 16299916
TI  - An audience with... Victoria G. Hale.

PMID- 16299917
TI  - From the analyst's couch: TLR-targeted therapeutics.

PMID- 16299918
TI  - Fresh from the pipeline: Ramelteon.

PMID- 16299919
TI  - US President releases long-awaited preparedness plan.

PMID- 16299920
TI  - Nations set out a global plan for influenza action.

PMID- 16299921
TI  - A vaccine in 50 days?

PMID- 16299923
TI  - Bibliography. Recent publications in hematological oncology.

PMID- 16299922
TI  - Survival of Escherichia coli O157:H7 in feces from corn- and barley-fed steers.
AB  - The survival of Escherichia coli O157:H7 in feces from steers fed corn (CO) or
      barley (BA) was evaluated at -10, +4 and +22 degrees C. Fecal pats were
      inoculated with a four-strain mixture of nalidixic-acid resistant E. coli O157:H7
      at two levels: 10(3) CFU g(-1) (low, L) and 105 CFU g(-1) (high, H). At -10
      degrees C, duration of survival of E. coli O157:H7 was reduced (p < 0.05) in CO-L
      (35 days) compared to BA-L (49 days), likely due to the effects of fecal volatile
      fatty acids in combination with a fecal pH of <6.5. At 4 degrees C, E. coli
      O157:H7 was detected in BA-H, CO-H, CO-L and BA-L for 77, 77, 56 and 63 days,
      respectively, with no difference (p > 0.05) observed in the duration of survival
      or rate of decline of E. coli O157:H7 among treatments. Survival of E. coli
      O157:H7 was twice as likely (p < 0.05) at 22 degrees C than at 4 degrees C and 
      10 degrees C. While pH and dry matter content increased, and volatile fatty acid
      concentrations decreased over 84 days at all three temperatures, these changes
      were most pronounced at 22 degrees C. Survival of E. coli O157:H7 for extended
      periods of time in feces from both corn- and barley-fed animals was demonstrated,
      thus fecal material may serve as a vector for the transmission of the organism.
      The greater survival of E. coli O157:H7 at 22 degrees C suggests that temperature
      may play a role in the seasonality of transmission and prevalence of this
      bacterium in feedlot cattle. The reported greater prevalence of E. coli O157:H7
      in cattle fed barley as compared to those fed corn does not appear to be related
      to elevated risk of transmission arising from differential survival of the
      bacterium in feces.

PMID- 16299924
TI  - Radiopharmaceuticals for the palliation of painful bone metastasis-a systemic
      review.
AB  - BACKGROUND AND PURPOSE: The purpose was to develop a systematic review that would
      address the following question: what is the role of radiopharmaceuticals in the
      palliation of metastatic bone pain in adults with uncomplicated, multifocal
      painful bone metastases whose pain is not controlled with conventional analgesic
      regimens? The outcomes of interest are pain response, analgesic consumption,
      overall survival, adverse effects and quality of life. MATERIALS AND METHODS: A
      systematic review of the English published literature was undertaken to provide
      evidence relevant to the above outcomes. RESULTS: Six randomized phase III
      trials, two randomized phase II trials and one randomized crossover trial of
      strontium-89 were reviewed. A randomized phase III trial comparing strontium-89
      plus cisplatin with strontium-89 plus placebo reported a significantly higher
      proportion of patients experiencing pain relief for a significantly longer
      duration with strontium-89 plus cisplatin. A randomized phase III trial comparing
      adjuvant strontium-89 with placebo following radiotherapy reported a higher
      proportion of pain-free patients with strontium-89. Patients who received
      strontium-89 also experienced fewer new sites of bone pain. A second, but
      underpowered study failed to confirm these results. In one randomized trial of
      strontium-89 versus radiotherapy (hemibody or local), patients treated with
      strontium-89 developed fewer new sites of pain. In a second trial comparing
      strontium-89 versus local radiotherapy, median overall survival was improved with
      radiotherapy, while pain response and time-to-progression were similar in the two
      groups. One randomized phase III trial reported no difference in pain relief
      between strontium-89 and placebo. Three randomized phase III trials and two
      randomized phase II trials investigating samarium-153 were reviewed. In a
      randomized phase III trial of three different doses of samarium-153, the pain
      responses were similar for all three doses. In a randomized phase III trial of
      two different doses of samarium-153 versus placebo, the complete pain response
      rate was significantly higher with the higher dose of samarium-153 compared with
      placebo. In a randomized phase III trial comparing samarium-153 with placebo,
      significant differences favouring samarium-153 were reported for pain and opiate
      use. In addition, one randomized phase III trial, two randomized phase II trials,
      one randomized crossover trial and 13 phase II or phase I trials of rhenium, one
      phase I trial of tin-117 m and one phase II trial of phosphorus-32 were reviewed.
      The majority of patients treated in trials of radiopharmaceuticals where
      histology was specified had metastatic breast cancer (approximately 5-10% of
      patients reported), metastatic hormone-refractory prostate cancer (80-90% of
      patients reported) or metastatic lung cancer (5-10% of patients reported).
      Information on histologic subtype was not available for a significant proportion
      of patients treated on trials (30-40% of patients reported). CONCLUSIONS: Use of
      single-agent radiopharmaceuticals (strontium-89 and samarium-153) should be
      considered as a possible option for the palliation of multiple sites of bone pain
      from metastatic cancer where pain control with conventional analgesic regimens is
      unsatisfactory and where activity on a bone scan of the painful lesions is
      demonstrated. Ongoing clinical research should seek to establish the benefit of
      newer radiopharmaceuticals and radiopharmaceuticals in combination with other
      systemic therapies.

PMID- 16299925
TI  - [Hematuria: 50-year vision. Interview with Dr. F. J. Sole Balcells and Dr. J. A.
      Martinez-Pineiro].

PMID- 16299926
TI  - Sources, vertical fluxes, and accumulation of aliphatic hydrocarbons in coastal
      sediments of the Rio de la Plata Estuary, Argentina.
AB  - Settling particles and underlying sediments collected at 1, 2.5 and 4 km off the
      metropolitan Buenos Aires coast were analyzed to evaluate the sources and
      accumulation of resolved (RES), unresolved (UCM), and biomarker aliphatic
      hydrocarbons. Sedimentary aliphatic concentrations (RES 0.11-14 microg x g(-1);
      UCM 0.1-800 microg x g(-1)) included variability associated with north-south
      gradients and an exponential offshore reduction. Highest concentrations were
      registered close to Buenos Aires port and sewer, compared to cleaner northern
      stations and southward sites affected by a seaward residue transport. Sediment
      traps deployed in the sewer area revealed large hydrocarbon (38 and 319 mg x m(
      2) x day(-1), RES and UCM) and total organic carbon fluxes (29 +/- 26 g x m(-2) x
      day(-1). The composition of RES and hopanes evaluated by principal component
      analysis indicated a consistent offshore gradient defined bythe relative
      contribution of lower vs higher molecular weight components. Distant sites showed
      decreasing proportions of petrogenic n-C(17-26) alkanes, isoprenoids, and C(20
      27) terpanes and relative enrichment of n-C(27,29,31,33) terrestrial plant
      alkanes and C(31-33) homohopanes. Sediment hydrocarbon profiles showed an average
      2-fold reduction down to 20 cm depth with preferential removal of lower molecular
      weight components and enrichment of n-C(23-35) alkanes and hopanes. Sediment
      inventories and trap depositional fluxes indicate the accumulation of 5800-9700
      tons of aliphatic hydrocarbons in the top 0-5 cm sediments with a strong
      interfacial alteration and selective preservation of refractory components: n
      C(13-22) (1.0%) < isoprenoids (3.2%) < n-C(23-35) (6.1%) < hopanes (47%)
      approximately UCM (50%), compared to intermediate stability of organic carbon
      (12%) and quantitative preservation of polychlorinated biphenyls (PCBs) (91%).

PMID- 16299927
TI  - Enhanced transmission of light through a circularly structured aperture.
AB  - Using the differential theory of light diffraction by finite cylindrical objects,
      we study light transmission through a small circular aperture in a metallic
      screen with concentric corrugation around the nanohole. Poynting vector maps in
      the region below the screen show that the field enhancement compared with an
      unstructured aperture is obtained with corrugation lying on the entrance face of
      the screen. Corrugation on the exit face leads to a more directional radiation
      close to the normal to the screen. The spectral dependence of the transmission
      shows a sharp maximum linked with surface plasmon excitation.

PMID- 16299928
TI  - Managing depression.

PMID- 16299930
TI  - Continuing concerns over acting FDA commissioner.

PMID- 16299929
TI  - Business must partner with government.

PMID- 16299931
TI  - European Union law puts tough restrictions on MRI.

PMID- 16299932
TI  - Assessment of subtle cognitive-communication deficits following acquired brain
      injury: A normative study of the Functional Assessment of Verbal Reasoning and
      Executive Strategies (FAVRES).
AB  - PRIMARY OBJECTIVE: To present a new measure, the Functional Assessment of Verbal
      Reasoning and Executive Strategies (FAVRES), with evidence for its reliability
      and validity in a normative study. The FAVRES is designed to evaluate the subtle
      cognitive-communication deficits of individuals with ABI. METHODS AND PROCEDURES:
      The FAVRES consists of four complex, contextually rich, verbal reasoning tasks
      that simulate everyday situations and require processing of text and discourse.
      Scoring considers the time, accuracy and justification of reasoning responses.
      The FAVRES scores of 52 adults with ABI were compared to those of 101 adults
      without ABI. OUTCOMES: FAVRES scores clearly differentiated the performances of
      individuals with and without ABI. Individuals with ABI were slower and less
      accurate in reasoning and presented fewer adequate rationales for their
      decisions. Inter-rater reliability for scoring was acceptable. CONCLUSIONS: The
      FAVRES provides a reliable, functional and quantifiable measure of the cognitive
      communication difficulties of individuals with ABI.

PMID- 16299933
TI  - Use of the Zung depression scale in patients with traumatic brain injury: 1 year
      post-injury.
AB  - OBJECTIVE: The purpose of this study was to examine if the physical disabilities
      of patients with traumatic brain injury (TBI) would influence the assessment of
      depression when using the Zung depression scale. METHOD: Patients with TBI (n=59)
      were assessed 1 year after injury for depression by both a psychiatrist and the
      use of the Zung depression scale. RESULTS: By psychiatric evaluation, seven of 17
      (41%) patients with severe TBI and one of 20 (5%) of the patients with moderate
      TBI were diagnosed with major depressive disorder. With the Zung depression
      scale, 10 of 17 (59%) patients with severe TBI met the cut-off (scored >55) for
      depression, whereas none of the patients with moderate (n=20) or mild (n=22) TBI
      did. The mean (SD) scores of the somatic scale were 2.91 (0.93), 2.49 (0.92) and
      1.25 (0.43) for each group. The mean scores of the affective scale were 2.58
      (0.90), 1.85 (0.79) and 1.24 (0.46). For patients with moderate (p<0.05) and
      severe (p<0.10) TBI, scores on the somatic items exceeded scores on their
      affective items. No difference in somatic and affective scale scores was noted
      for the patients with mild TBI. CONCLUSION: The increased endorsement of somatic
      results may be the somatic difficulties associated with traumatic brain injury.

PMID- 16299934
TI  - Reintegration after severe brain injury: a retrospective study.
AB  - PRIMARY OBJECTIVE: The evaluation of school and work reintegration of patients
      following severe brain injury and of the relationship between the most common
      (early and late) prognostic indicators and reintegration itself. RESEARCH DESIGN:
      A retrospective study on a population of 353 patients consecutively admitted to
      an intensive rehabilitation unit (S. Cuore Hospital, Negrar, Italy) from 1991
      1999. METHODS AND PROCEDURES: Evaluation of school and work outcome in this
      population up to December 2001 (follow-up from 2-10 years post-trauma). Data
      collection was made using the EBIS (European Brain Injury Society) protocol.
      RESULTS: In December 2001, 53% of those previously working had returned to
      competitive work; 76.5% of students were continuing with their studies or had
      progressed into work. There was a significant difference between employed and non
      employed groups in terms of GCS, post-traumatic amnesia (PTA), in-patient
      rehabilitation length of stay (LOS) and GOS at 6 and at 12 months post-injury.
      CONCLUSIONS: The data confirm the predictive value of the indices used regarding
      work reintegration in TBI patients. Nevertheless, prolonged and intensive
      rehabilitation programmes can lead to high re-employment rates in patients whose
      initial prognosis seemed very poor.

PMID- 16299935
TI  - Opinion about post-concussion syndrome in health professionals.
AB  - OBJECTIVE: To compare opinion about post-concussion syndrome (PCS) in accident
      and emergency doctors, clinical neuropsychologists and neurosurgeons. METHOD: A
      UK postal survey was sent to all accident and emergency doctors, neurosurgeons
      and clinical neuropsychologists listed by their professional bodies. Predictions
      of symptom complaint were made from a vignette about minor traumatic brain injury
      and a questionnaire about PCS-symptoms, cause, recovery and treatment. RESULTS:
      All professional groups named headache, attention and memory difficulties as most
      common symptoms. Clinical neuropsychologists listed more symptoms at recall, more
      often achieved 'caseness' (Diagnostic and Statistical Manual-IV or International
      Classification of Diseases-10 criteria) and were more optimistic about treatment
      effectiveness. Neurosurgeons were more pessimistic about recovery. Organic
      factors were most frequently cited as the main cause of PCS, followed by
      emotional factors and then compensation factors. CONCLUSIONS: There was fair
      consistency between professional groups regarding PCS. Differences may reflect
      differing clinical roles between the professions, in terms of early care and late
      rehabilitation. The usefulness of the concept of PCS is discussed. All groups and
      particularly those working in acute settings may benefit from further information
      about minor brain injury including the effectiveness of psychological
      interventions.

PMID- 16299936
TI  - A case of fulminant "talc pneumoconiosis": where is the smoking gun?

PMID- 16299937
TI  - Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery.

PMID- 16299938
TI  - [Prosthodontics perspective in the near future].

PMID- 16299939
TI  - Case 23-2005: a man with a mass in the liver.

PMID- 16299940
TI  - Case 23-2005: a man with a mass in the liver.

PMID- 16299941
TI  - Zoledronic acid(ZOMETA): a significant improvement in the bone metastases.

PMID- 16299942
TI  - Early tymp tubes do not improve outcomes after 3+ years.

PMID- 16299943
TI  - Diagnosing pulmonary embolism: results vary among the tests.

PMID- 16299944
TI  - Guideline for chronic constipation management.

PMID- 16299945
TI  - Clinical assessment of limited value in DVT diagnosis.

PMID- 16299946
TI  - Home glucose monitoring makes little difference in type 2 diabetes.

PMID- 16299947
TI  - Medicare program; revisions to payment policies under the physician fee schedule
      for calendar year 2006 and certain provisions related to the Competitive
      Acquisitions Program of outpatient drugs and biologicals under Part B. Final rule
      with comment.
AB  - This rule addresses Medicare Part B payment policy, including the physician fee
      schedule that are applicable for calendar year (CY) 2006; and finalizes certain
      provisions of the interim final rule to implement the Competitive Acquisition
      Program (CAP) for Part B Drugs. It also revises Medicare Part B payment and
      related policies regarding: Physician work; practice expense (PE) and malpractice
      relative value units (RVUs); Medicare telehealth services; multiple diagnostic
      imaging procedures; covered outpatient drugs and biologicals; supplemental
      payments to Federally Qualified Health Centers (FQHCs); renal dialysis services;
      coverage for glaucoma screening services; National Coverage Decision (NCD)
      timeframes; and physician referrals for nuclear medicine services and supplies to
      health care entities with which they have financial relationships. In addition,
      the rule finalizes the interim RVUs for CY 2005 and issues interim RVUs for new
      and revised procedure codes for CY 2006. This rule also updates the codes subject
      to the physician self-referral prohibition and discusses payment policies
      relating to teaching anesthesia services, therapy caps, private contracts and opt
      out, and chiropractic and oncology demonstrations. As required by the statute, it
      also announces that the physician fee schedule update for CY 2006 is -4.4
      percent, the initial estimate for the sustainable growth rate for CY 2006 is 1.7
      percent and the conversion factor for CY 2006 is $36.1770.

PMID- 16299948
TI  - Cancer risks in a UK benzene exposed cohort.

PMID- 16299949
TI  - Medicare's new drug plan: the right choice for you?

PMID- 16299950
TI  - Flu 2005: essential info for staying safe.

PMID- 16299951
TI  - Rising pressure: hospital emergency departments as barometers of the health care
      system.
AB  - Pressures--ranging from persuading specialists to provide on-call coverage to
      dealing with growing numbers of patients with serious mental illness--are
      building in already-crowded hospital emergency departments (EDs) across the
      country, according to findings from the Center for Studying Health System
      Change's (HSC) 2005 site visits to 12 nationally representative communities. As
      the number of ED visits rises significantly faster than population growth, many
      hospitals are expanding emergency department capacity. At the same time,
      hospitals face an ongoing nursing shortage, contributing to tight inpatient
      capacity that in turn hinders admitting ED patients. In their role as hospitals'
      "front door" for attracting insured inpatient admissions, emergency departments
      also increasingly are expected to help hospitals compete for insured patients
      while still meeting obligations to provide emergency care to all-comers under
      federal law. Failure to address these growing pressures may compromise access to
      emergency care for patients and spur already rapidly rising health care costs.

PMID- 16299952
TI  - Building a healthier future: partnering to improve public health.

PMID- 16299954
TI  - For the benefit of all: ensuring immigrant health and well-being.

PMID- 16299953
TI  - In harm's way: aiding children exposed to trauma.

PMID- 16299955
TI  - [Does surveillance of patients with Barrett's esophagus improve survival?].

PMID- 16299956
TI  - [Prognostic significance of cyclooxygenase 2 expression in adenocarcinoma of the
      esophagus].

PMID- 16299960
TI  - Are you working too hard? A conversation with mind/body researcher Herbert
      Benson.
AB  - Stress is an essential response in highly competitive environments. Before a
      race, before an exam, before an important meeting, your heart rate and blood
      pressure rise, your focus tightens, you become more alert and more efficient. But
      beyond a certain level, stress overloads your system, compromising your
      performance and, eventually, your health. So the question is: When does stress
      help and when does it hurt? To find out, HBR talked with Harvard Medical School
      professor Herbert Benson, M.D., founder of the Mind/Body Medical Institute.
      Having spent more than 35 years conducting worldwide research in the fields of
      neuroscience and stress, Benson is best known for his 1975 best seller The
      Relaxation Response, in which he describes how the mind can influence stress
      levels through such tools as meditation. His most recent research centers on what
      he calls"the breakout principle," a method by which stress is not simply reduced
      but carefully controlled so that you reap its benefits while avoiding its
      dangers. He describes a four-step process in which you first push yourself to the
      most productive stress level by grappling intently with a problem. Next, just as
      you feel yourself flagging, you disengage entirely by doing something utterly
      unrelated-going for a walk, petting a dog, taking a shower. In the third step, as
      the brain quiets down, activity paradoxically increases in areas associated with
      attention, space-time concepts, and decision making, leading to a sudden,
      creative insight-the breakout. Step four is achievement of a "new-normal state,"
      in which you find that the improved performance is sustained, sometimes
      indefinitely. As counterintuitive as this research may seem, managers can
      doubtless recall times when they've had an "aha" moment at the gym, on the golf
      course, or in the shower. What Benson describes here is a way to tap into this
      invaluable biological tool whenever we want.

PMID- 16299961
TI  - Innovation versus complexity: what is too much of a good thing?
AB  - What's the number of product or service offerings that would optimize both your
      revenues and your profits? For most firms, it's considerably lower than the
      number they offer today. The fact is, companies have strong incentives to be
      overly innovative in new product development. But continual launches of new
      products and line extensions add complexity throughout a company's operations,
      and as the costs of managing that complexity multiply, margins shrink. To
      maximize profit potential, a company needs to identify its innovation fulcrum,
      the point at which an additional offering destroys more value than it creates.
      The usual antidotes to complexity miss their mark because they treat the problem
      on the factory floor rather than at its source: in the product line. Mark
      Gottfredson and Keith Aspinall of Bain & Company present an approach that goes
      beyond the typical Six Sigma or lean-operations program to root out complexity
      hidden in the value chain. The first step is to ask, What would our company look
      like if it made and sold only a single product or service? In other words, you
      identify your company's equivalent of Henry Ford's one-size-fits-all Model T-for
      Starbucks, it might be a medium-size cup of coffee; for a bank, a simple checking
      account-and then determine the cost of producing that baseline offering. Next,
      you add variety back into the business system, product by product, and carefully
      forecast the resulting impact on sales as well as the cost implications across
      the value chain. When the analysis shows the costs beginning to overwhelm the
      added revenues, you've found your innovation fulcrum. By deconstructing their
      companies to a zero-complexity baseline, managers can break through
      organizational resistance and deeply entrenched ways of thinking to find the
      right balance between innovation and complexity.

PMID- 16299962
TI  - Leadership in your midst: tapping the hidden strengths of minority executives.
AB  - All companies value leadership-some of them enough to invest dearly in
      cultivating it. But few management teams seem to value one engine of leadership
      development that is right under their noses, churning out the kind of talent they
      need most. It's the complicated, overburdened but very rich lives of their
      minority managers. Minority professionals-particularly women of color-are called
      upon inordinately to lend their skills and guidance to activities outside their
      jobs. Sylvia Ann Hewlett, who heads the Center for Work-Life Policy, and her
      coauthors, Carolyn Buck Luce of Ernst & Young and Cornel West of Princeton,
      present new research on the extent to which minority professionals take on
      community service and other responsibilities outside the workplace and more than
      their share of recruiting, mentoring, and committee work within the workplace.
      These invisible lives, argue the authors, can be a source of competitive strength
      if companies can learn to recognize and further cultivate the cultural capital
      they represent. But it's hard to convince minority professionals that their
      employer respects and values their off-hours responsibilities. A lack of trust
      keeps many people from revealing much about their personal lives. The authors
      outline four ways companies can leverage hidden skills: Develop a new level of
      awareness of minority professionals' invisible lives; appreciate the outsize
      burdens these professionals carry and try to lighten them; build trust by putting
      teeth into diversity goals; and, to finish the job of leadership development,
      help minorities reflect on their off-hours experiences, extract and generalize
      the lessons, and apply what's been learned in other settings.

PMID- 16299963
TI  - You have more capital than you think.
AB  - Senior executives typically delegate the responsibility for managing a firm's
      derivatives portfolio to in-house financial experts and the company's financial
      advisers. That's a strategic blunder, argues this Nobel laureate, because the
      inventiveness of modern financial markets makes it possible for companies to
      double or even triple their capacity to invest in their strategic assets and
      competencies. Risks fall into two categories: either a company adds value by
      assuming them on behalf of its shareholders or it does not. By hedging or
      insuring against non-value-adding risks with derivative securities and contracts,
      thereby removing them from what the author calls the risk balance sheet, managers
      can release equity capital for assuming more value-adding risk. This is not just
      a theoretical possibility. One innovation-the interest rate swap, introduced
      about 20 years ago-has already enabled the banking industry to dramatically
      increase its capacity for adding value to each dollar of invested equity capital.
      With the range of derivative instruments growing, there is no reason why other
      companies could not similarly remove strategic risks, potentially creating
      billions of dollars in shareholder value. The possibilities are especially
      important for private companies that have no access to public equity markets and
      therefore cannot easily increase their equity capital by issuing more shares. The
      author describes how derivative contracts of various kinds are already being
      employed strategically to mitigate or eliminate various risks. He also shows how
      companies can use the risk balance sheet to identify risks they should not bear
      directly and to determine how much equity capacity they can release for assuming
      more value-adding risk.

PMID- 16299964
TI  - Hiring for smarts.
AB  - Yes, it's nice when a leader is charismatic and confident. And a great resume can
      tell you a lot about a person's knowledge and experience. But such assets are no
      substitute for sheer business intelligence, and they reveal very little about a
      leader's ability to consistently reach the "right" answer. How can hiring
      managers flag individuals with such smarts? Historically, the only reliable
      measure of brainpower has been the standard IQ test, which is rarely used in
      business settings because of the specific subjects it tests for-math, reading,
      and spatial reasoning-and because of its multiple-choice format. Despite its
      shortcomings, the standard IQ test is still a better predictor of managerial
      success than any other assessment tool companies currently use, Justin Menkes
      argues. It's true that there isn't a version of IQ testing that applies to the
      corporate world, but in rejecting IQ tests altogether, hiring managers have
      thwarted their own attempts to identify true business stars. The author defines
      the specific subjects that make up "executive intelligence"-namely, accomplishing
      tasks, working with people, and judging oneself. He describes how to formulate
      questions to test job candidates for their mastery of these subjects, offering
      several examples based on real situations. Knowledge questions, such as those
      used in standard behavioral interviews, require people to recite what they have
      learned or experienced; intelligence questions call for individuals to
      demonstrate their abilities. Therefore, the questions in an executive
      intelligence test shouldn't require specific industry expertise or experience;
      any knowledge they call for must be rudimentary and common to all executives. And
      the questions should not be designed to ask whether the candidate has a
      particular skill; they should be configured so that the candidate will have to
      demonstrate that skill in the course of answering them.

PMID- 16299965
TI  - The perfect message at the perfect moment.
AB  - Marketers planning promotional campaigns ask questions to boost the odds that the
      messages will be accepted: Who should receive each message? What should be its
      content? How should we deliver it? The one question they rarely ask is, when
      should we deliver it? That's too bad, because in marketing, timing is arguably
      the most important variable of all. Indeed, there are moments in a customer's
      relationship with a business when she wants to communicate with that business
      because something has changed. If the company contacts her with the right message
      in the right format at the right time, there's a good chance of a warm reception.
      The question of "when" can be answered by a new computer-based model called
      "dialogue marketing," which is, to date, the highest rung on an evolutionary
      ladder that ascends from database marketing to relationship marketing to one-to
      one marketing. Its principle advantages over older approaches are that it is
      completely interactive, exploits many communication channels, and is
      "relationship aware": that is, it continuously tracks every nuance of the
      customer's interaction with the business. Thus, dialogue marketing responds to
      each transition in that relationship at the moment the customer requires
      attention. Turning a traditional marketing strategy into a dialogue-marketing
      program is a straightforward matter. Begin by identifying the batch
      communications you make with customers, then ask yourself what events could
      trigger those communications to make them more timely. Add a question or call to
      action to each message and prepare a different treatment or response for each
      possible answer. Finally, create a series of increasingly urgent calls to action
      that kick in if the question or call to action goes unanswered by the customer.
      As dialogue marketing proliferates, it may provide the solid new footing that
      Madison Avenue seeks.

PMID- 16299966
TI  - Scanning the periphery.
AB  - Companies often face new rivals, technologies, regulations, and other
      environmental changes that seem to come out of left field. How can they see these
      changes sooner and capitalize on them? Such changes often begin as weak signals
      on what the authors call the periphery, or the blurry zone at the edge of an
      organization's vision. As with human peripheral vision, these signals are
      difficult to see and interpret but can be vital to success or survival.
      Unfortunately, most companies lack a systematic method for determining where on
      the periphery they should be looking, how to interpret the weak signals they see,
      and how to allocate limited scanning resources. This article provides such a
      method-a question-based framework for helping companies scan the periphery more
      efficiently and effectively. The framework divides questions into three
      categories: learning from the past (What have been our past blind spots? What
      instructive analogies do other industries offer? Who in the industry is skilled
      at picking up weak signals and acting on them?); evaluating the present (What
      important signals are we rationalizing away? What are our mavericks, outliers,
      complainers, and defectors telling us? What are our peripheral customers and
      competitors really thinking?); and envisioning the future (What future surprises
      could really hurt or help us? What emerging technologies could change the game?
      Is there an unthinkable scenario that might disrupt our business?). Answering
      these questions is a good first step toward anticipating problems or
      opportunities that may appear on the business horizon. The article concludes with
      a self-test that companies can use to assess their need and capability for
      peripheral vision.

PMID- 16299967
TI  - Defensive marketing: how a strong incumbent can protect its position.
AB  - There has been a lot of research on marketing as an offensive tactic-how it can
      help companies successfully launch new products, enter new markets, or gain share
      with existing products in their current markets. But for nearly every new product
      launch, market entrant, or industry upstart grabbing market share, there is an
      incumbent that must defend its position. And there has been little research on
      how these defenders can use marketing to preemptively respond to new or
      anticipated threats. John H. Roberts outlines four basic types of defensive
      marketing strategies: positive, inertial, parity, and retarding. With the first
      two, you establish and communicate your points of superiority relative to the new
      entrant; with the second two, you establish and communicate strategic points of
      comparability with your rival. Before choosing a strategy, you need to assess the
      weapons you have available to protect your market position-your brand identity,
      the products and services that support that identity, and your means of
      communicating it. Then assess your customers' value to you and their
      vulnerability to being poached by rivals. The author explains how Australian
      telecommunications company Telstra, facing deregulation, used a combination of
      the four strategies (plus the author's customer response model) to fend off
      market newcomer Optus. Telstra was prepared, for instance, to reach deep into its
      pockets and engage in a price war. But the customer response model indicated that
      a parity strategy-in which Telstra would offer lower rates on some routes and at
      certain times of day, even though its prices, on average, were higher than its
      rival's-was more likely to prevent consumers from switching. Ultimately, Telstra
      was able to retain several points of market share it otherwise would have lost.
      The strategies described here, though specific to Telstra's situation, offer
      lessons for any company facing new and potentially damaging competition.

PMID- 16299968
TI  - [Large animal practitioners' perspective of their patients and clients and their
      professional responsibilities].
AB  - Veterinarians have obligations towards both the animals they treat and their
      clients, the owners of the animals. Veterinarians have complicated, and often
      conflicting, relationships with both groups. In this article, Q-methodology was
      used as a method for discourse analysis to determine how Dutch large animal
      practitioners conceptualize animals and their owners and their professional
      responsibilities towards both. The article focuses on four different perspectives
      that Dutch veterinarians have of their animal patients and their owners, and of
      their professional duties and responsibilities.

PMID- 16299969
TI  - [Mistake?].

PMID- 16299970
TI  - [A legal case: a smudge on the record or a statistical risk].

PMID- 16299971
TI  - [Women in the veterinary clinic: problem or a challenge?].

PMID- 16299972
TI  - [BVD-prevention: difference in tackling the problem].

PMID- 16299973
TI  - [Department of animals, science and society plays an important role in veterinary
      education. Interview by Marianne M. Sloet van Oldruitenborgh-Oosterbaan].

PMID- 16299974
TI  - [Instruments, books and other objects memorable to (almost) forgotten opinions,
      therapies, buildings, et cetera. The electro-ejaculator].

PMID- 16299975
TI  - [Avian influenza and the role of the KNMvD].

PMID- 16299976
TI  - Influenza economics. Providers and suppliers who usually reap big profits during
      flu season might find that a pandemic could backfire on their bottom lines.
AB  - Health and Human Services Secretary Mike Leavitt, right, spoke about avian
      influenza at the National Press Club in Washington last week. President Bush's
      plan involves asking Congress to invest billions of dollars in development,
      production and stockpiling of antiviral drugs and vaccines in case the flu strain
      becomes a pandemic. HHS hopes to stockpile enough of vaccine to inoculate 20
      million Americans.

PMID- 16299977
TI  - Public health. Nothing to sneeze at.

PMID- 16299978
TI  - Will it last? Hospital profits hit an all-time high in 2004.

PMID- 16299979
TI  - Increasing the pressure. AHA seeks HHS advisory on JCAHO data mining.

PMID- 16299980
TI  - Strong-arming agencies. JCAHO gets into the staffing certification business.

PMID- 16299981
TI  - The first of many? Ore. system settles Scruggs' charity-care lawsuit.

PMID- 16299982
TI  - Public health. Preparing for the worst.

PMID- 16299983
TI  - Purchase skirts trial. Instead of battling in court, Aultman buys PCM.

PMID- 16299984
TI  - No savings, but plenty of pain. Florida's Medicaid plan would hurt the poor and
      their healthcare providers.

PMID- 16299985
TI  - Don't rebuild--rethink. Gulf Coast can be a model of high-tech healthcare
      delivery.

PMID- 16299987
TI  - By the numbers. Largest MHA programs ranked by total number of students.

PMID- 16299986
TI  - Two in one. The CMS' strict admissions criteria make long-term acute-care
      hospitals consider co-locating with skilled-nursing facilities.

PMID- 16299988
TI  - Straight talk. New approaches in healthcare.
AB  - Not-for-profit health systems are under the public microscope. Sen. Charles
      Grassley, (D-Iowa) chairman of the Senate Finance Committee, has been critical of
      the charity care and billing practices of not-for-profit health systems, and vows
      to introduce legislation to correct abuses throughout the tax-exempt sector. The
      House has studied the issue as well. Not-for-profit health systems also have been
      accused in hundreds of lawsuits of overcharging uninsured patients and
      aggressively pursuing debt collection. In this installment of Straight Talk, we
      explore the issues surrounding tax-exempt status and how health systems should
      publicize their charitable work. Modern Healthcare and PricewaterhouseCoopers
      present Straight Talk. The session on charity care and tax-exempt status was held
      on October 4, 2005 at Modern Healthcare's Chicago headquarters. Fawn Lopez,
      publisher of Modern Healthcare, was the moderator.

PMID- 16299990
TI  - A man with an antiflu plan.

PMID- 16299989
TI  - Grim and grimmer. Medical groups see margins thin, says MGMA.

PMID- 16299991
TI  - Skin deep. As the body's largest organ, skin is a powerful yet unappreciated
      veneer.

PMID- 16299992
TI  - First alert. A disease may announce its presence on the skin.

PMID- 16299993
TI  - Not so sunny spots. You can still get skin cancer even if you haven't spent a
      lifetime outdoors.

PMID- 16299994
TI  - Turn back the clock. All sorts of products promise to trim away years--without
      using a knife.

PMID- 16299995
TI  - Oh, no! Not at my age!

PMID- 16299996
TI  - The thrill is gone. Sure, that butterfly is cute. But will you still be happy
      with it tomorrow?

PMID- 16299998
TI  - [A case of skin myiasis].

PMID- 16299997
TI  - [Expression of truncated Toxoplasma gondii GRA8 in the prokaryotic expression
      plasmids].
AB  - OBJECTIVE: To construct the prokaryotic recombinant expression plasmids of
      Toxoplasma gondii GRA8 and analyze their expression in E. coli containing the
      prokaryotic recombinant plasmids. METHODS: The full gene and its truncated
      fragment of GRA8 were amplified by PCR from T. gondii genomic DNA, and cloned
      into pMD18-T vector. The right genes in positive clones sequenced with ABI
      PRISMTM 377XL DNA Sequencer were digested with restrictive endonucleases and
      subcloned into pGEX-4T-2. The recombinant plasmids were transformed into E. coli
      JM109. The recombinant clones were characterized by PCR and digested with
      restriction endonucleases. Positive clones were induced with IPTG to express
      target protein and characterized by SDS-PAGE. The recombinant protein was
      purified from E. coli lysate by affinity chromatography and SDS-PAGE. The
      immunological activity of this protein was analyzed by Western blotting. RESULTS:
      The gene fragments encoding GRA8 were amplified by PCR from T. gondii genomic
      DNA. The inserts of GRA8 in positive clones were coincident with the original
      sequence of GRA8 gene from GenBank. The recombinant expression plasmids were
      constructed through subcloning the right inserts of GRA8 into pGEX-4T-2. The
      expression level of GRA8 from the recombinant expression plasmids in E. coli was
      low, and there was almost no full-length GRA8 expressed in E. coli. The purified
      protein reacted with the sera from rabbits infected with T. gondii RH strain.
      CONCLUSION: The expression level of GRA8 from the recombinant expression plasmids
      in E. coli is low and the purified truncated GRA8 shows certain antigenicity.

PMID- 16299999
TI  - [The point mutations in Pfcrt and Pfmdr1 genes in Plasmodium falciparum isolated
      from Hainan Province].
AB  - OBJECTIVE: To evaluate the point mutations in Pfcrt and Pfmdr1 genes in
      Plasmodium falciparum isolated from Hainan Province. METHODS: Nested polymerase
      chain reaction and restriction fragment length polymorphism were used to detect
      the point mutations at codon 76 of Pfcrt and at codon 86, 1246 of Pfmdr1 in P.
      falciparum isolates. Chloroquine resistance was measured by the in vitro
      microtest recommended by WHO. RESULTS: In 36 samples tested, 28 were successfully
      amplified for Pfcrt, 64.3% of them carried mutant allele at codon 76, 21.4% with
      wild allele K76 and 14.3% with mixed allele mutation. While for Pfmdr1, 3.4%
      isolates displayed the 86Y mutation, 89.7% with wild allele N86 and 6.9% with the
      mixed alleles in 29 isolates which were amplified successfully for N86Y. No point
      mutation in Pfmdr1 at codon 1246 was found in 13 isolates from the total 36
      samples. By the in vitro test, 72.2% (26/36) showed resistance to chloroquine.
      The 76T and 86Y mutant alleles were present in both in vitro susceptible and
      resistant isolates. There was a significant difference between susceptible and
      resistant isolates carrying 76T mutant codon (P < 0.05), but no significant
      difference was found in Pfmdr1 (P < 0.05). CONCLUSION: There is a significant
      difference of the 76T prevalence in Pfcrt gene between the susceptible isolate
      and resistant one of P. falciparum to chloroquine in vitro. The Pfcrt 76T may be
      used as a predictive marker for chloroquine resistance surveillance.

PMID- 16300000
TI  - [Tag primer-nested/ multiplex PCR for detection of Plasmodium falciparum and
      Plasmodium vivax].
AB  - OBJECTIVE: To establish a sensitive, simple to use and low noise nested/multiplex
      PCR for simultaneously detection of Plasmodium falciparum (Pf) and Plasmodium
      vivax (P.v). METHODS: The tag primer amplification technique, software Primer
      Premier 5.0, NCBI-BLAST web resources and the matrix test were used to optimize
      the nested/multiplex PCR for detection of P.f and P.v with filter paper blood
      samples taken from malaria patients diagnosed by microscopy, and the results of
      the optimized nested/multiplex PCR and microscopy were evaluated. RESULTS: The
      sensitivity of the optimized PCR, determined by the examination of imitative
      filter paper blood samples, was about 1-2 parasites / microl for P.f and 5-10
      parasites / microl for P.v. Primer-dimer and other PCR noise were removed. When
      71 field filter paper blood samples taken from microscopically diagnosed patients
      (24 P.f, 47 P.v) were examined, the concordance between the optimized PCR and
      microscopy was 875% for Pf and 100% for P.v. CONCLUSION: The nested/multiplex PCR
      optimized by tag primer amplification technique is simple, with low noise and
      being able to detect Pf and P.v simultaneously. It is more sensitive in detecting
      cases with low parasitaemia and more accurate in identifying Plasmodium species
      than microscopy.

PMID- 16300002
TI  - [Morphological observation on the eggs and larvae of Thelazia callipaeda from
      human eye].

PMID- 16300001
TI  - [Detection of anti-Trichinella spiralis antibody by indirect ELISA using
      recombinant protein as antigen].
AB  - OBJECTIVE: To study the specificity, sensitivity of diagnostic antigen for
      Trichinella spiralis (T.s). METHODS: T668 recombinant protein from highly
      efficient expression of newborn larvae stage-specific gene of T.s in E. coli as
      diagnostic antigen. By using negative and positive sera from rabbit, pig, human
      as the first antibody, and goat-anti-rabbit IgG, goat-anti-pig IgG, goat-anti
      human IgG labeled with HRP as the secondary antibody, indirect ELISA method was
      established for detecting anti-T.s antibody, while excretory-secretory (ES)
      antigen of T.s muscle larvae was used as control. RESULTS: Sera from rabbit, pig
      and human were detected by T668 recombinant protein as antigen, which showed a
      positive rate of 100% with 0.016 microg/well. There was no difference on the
      results between the T668 recombinant antigen and the ES antigen for diagnosing
      T.s-infection. CONCLUSION: The T668 recombinant antigen is promising in
      substituting ES antigen in the detection of anti-T.s antibody.

PMID- 16300004
TI  - [ A survey on intestinal parasitic infections among Uygur pupils in Kashgar and
      Hetian of Xinjiang].

PMID- 16300003
TI  - [Comparative study on the resting habit of Anopheles minimus A and Anopheles
      minimus C in Yunnan Province].
AB  - OBJECTIVE: To compare the difference of resting habitat between Anopheles minimus
      A and An. minimus C in Yunnan Province. METHODS: A village was selected in Mengla
      and Yuanjiang County respectively to collect mosquitoes by hanging ultraviolet
      lamps inside the cattle pen and human dwellings. The samples were identified by
      multiplex-PCR after morphological examination. Suspicious An. minimus A/C hybrid
      samples were identified by PCR-ASA, PCR-RFLP and D3 region sequence. RESULTS: In
      human dwellings, the proportion of An. minimus A and C was 21.35% and 78.65%, and
      in cattle pen, 28.54% and 71.46% respectively. As for the An. minimus A/C hybrid,
      the result of PCR-ASA and PCR-RFLP displayed the pattern of both An. minimus A
      and An. minimus C (PCR-ASA: 376, 294 and 112 bp, PCR-RFLP:108, 268 and 376 bp),
      the D3 sequence displayed heterozygosis in the variation place of An. minimus A
      and An. minimus C, which means that the hybrid possesses the signal of both An.
      minimus A and An. minimus C. CONCLUSION: There is no resting habit difference
      between An. minimus A and An. minimus C in Yunnan Province. In Mengla County, 5
      An. minimus A/C hybrids have been found for the first time.

PMID- 16300005
TI  - [The adjuvant effect of IL-12 on protective immunity of Schistosoma japonicum
      fatty acid binding protein (Sj14FABP)].
AB  - OBJECTIVE: To study the immune protection of Schistosoma japonicum fatty acid
      binding protein (Sj14FABP) DNA vaccine enhanced by IL-12. METHODS: The
      recombinant plasmids pVIVO2-Sj14FABP and pVIVO2-IL12-Sj14FABP were constructed
      respectively, and were prepared on a large scale after identification. 48 male
      BALB/c mice were divided into 4 groups randomly. In group A, B, C, and D, each
      mouse was injected intramuscularly with 100 microl 0.9% NaCl, 100 microg pVIVO2,
      100 microg pVIVO2-Sj14FABP and 100 microg pVIVO2-IL12-Sj14FABP respectively. 30
      days after immunization each mouse was challenged with 40 +/- 2 cercariae of S.
      japonicum. On day 45 after challenge, all mice were sacrificed to count the
      number of recovered adult worms and the hepatic eggs. Sera from mice were used to
      detect IgG antibody. The production of IL-2, IL-4 and IFN-gamma in the
      supernatant of spleen cells was observed by means of sandwich ABC-ELISA. RESULTS:
      The recombinant plasmids pVIVO2-Sj14FABP and pVIVO2-IL12-Sj14FABP were
      constructed. The worm reduction rate in group C and D was 24.11% and 39.4%, as
      well as liver egg reduction rate of 27.2% and 32.8% respectively. The level of IL
      2 and IFN-gamma in group D increased significantly, while IL-4 secretion
      decreased (P < 0.01). 30 days after immunization, no higher titer of IgG antibody
      was shown in all groups. Furthermore, no significant difference on the level of
      IgG was found among the groups (P > 0.05). CONCLUSION: Sj14FABP DNA vaccine
      induces partial protective immunity in BALB/c mice. IL-12 drives the immune
      response toward a Th1 direction, and enhances the protective immune effect of the
      vaccine.

PMID- 16300007
TI  - [The colonoscopy in diagnosis of 10 cases of cecum ancylostomiasis].

PMID- 16300006
TI  - [Fusion expression and antigenicity analysis of miracidial antigen from eggs of
      Schistosoma japonicum].
AB  - OBJECTIVES: To express the miracidial antigen from eggs of Schistosoma japonicum
      (Chinese mainland strain) (SjMP10), and investigate the role of the miracidial
      antigen during the hepatic granuloma formation of schistosomiasis. METHODS: A
      pair of specific primers was designed and synthesized according to the nucleotide
      sequence of the open reading frame of the miracidial antigen gene. The open
      reading frame of the miracidial antigen gene was amplified, digested by
      restrictive enzyme (BamHI, SolI), and cloned directly into the expression plasmid
      pGEX-4T-3 to construct the recombinant plasmid. The recombinant plasmids were
      transformed into E. coli BL21(DE3), and induced by IPTG to express the fusion
      protein of GST-SjMP10. The expressed fusion protein was purified by electric
      elution method, and its antigenicity was examined by Western blotting and
      lymphocyte proliferation test. RESULTS: The gene of miracidial antigen was cloned
      into the expression plasmid pGEX-4T-3. After induced by IPTG, the recombinant
      expressed a fusion protein of GST-SjMP10, with a molecular weight of 39 000
      approximately. The purified fusion protein showed proper antigenicity that could
      be recognized by the sera of rabbits heavily infected by Schistosoma japonicum
      and could stimulate the proliferation of splenic lymphocytes of infected BALB/c
      mice. CONCLUSION: The miracidial antigen from eggs of Schistosoma japonicum was
      expressed successfully.

PMID- 16300008
TI  - [Oral mixed DNA vaccine protects mice from infection of Toxoplasma gondii].
AB  - OBJECTIVE: To examine the immune response in BALB/c mice induced by oral mixed
      Toxoplasma gondii DNA vaccine delivered by live attenuated Salmonella
      typhimurium. METHODS: Gene fragments SAG1 and SAG2 were amplified from the
      genomic DNA of T. gondii RH strain by PCR and were subcloned into pcDNA3.1(+/-)
      eukaryotic expression vector. The positive recombinant plasmid was transformed
      into aroA- and aroD-attenuated Salmonella typhimurium BRD509 (BRD509/pSAG1/SAG2).
      After screened by PCR, restrictive enzyme digestion and sequencing, recombinant
      Salmonella strain was used to immunize BALB/c mice by i.g. route, three times at
      2-week interval. Humoral and cellular responses were assayed using ELISA for
      determining antibody, IFN-gamma and IL-4. MTT assay was used to detect the
      proliferation activity of T lymphocytes and the activity of NK killers. FCM was
      also used to sort the lymphocyte subsets of spleen cells All mice were then
      infected with highly virulent RH tachyzoites of T. gondii intraperitoneally.
      RESULTS: Significant increase of specific IgG level was observed in immunized
      mice with a titer of 1:100. Proliferation activity of specific NK cells and T
      lymphocytes was highly enhanced in BRD509/ pSAG1/SAG2 vaccinated mice: the
      killing activity of NK cells was 85% +/- 7%, the proliferation SI of T
      lymphocytes was 2.83, which resulted in a 5 days longer survival time than mice
      in control group after challenge infection. CONCLUSION: The oral mixed DNA
      vaccine delivered by attenuated Salmonella typhimurium shows an immunoprotection
      against T. gondii in mice.

PMID- 16300010
TI  - [Study on the relationship of immune status with severity of schistosomiasis
      japonica in fishermen in the Dongting Lake].
AB  - OBJECTIVE: To investigate the relationship of the immune status and the intensity
      of infection or the severity of the hepatosplenic pathology among fishermen with
      schistosomiasis japonica in the Dongting Lake region. METHODS: Inquiring and
      physical examination (IPE), stool examination, B-ultrasonography of the liver and
      spleen, flow cytometry, turbidimetry and ELISA were undertaken to acquire or
      determine the intensity of infection (EPG in stool), pathological change in the
      liver and spleen and the level of cellular and humoral immunity. Data were
      analyzed with SPSS 10.0 statistics software. RESULTS: Compared with subjects from
      non-endemic area, the CD4+ T cells and the CD4+/CD8+ ratio in fishing population
      in the endemic area significantly decreased. The decrease of the CD4+/CD8+ ratio
      was more significant among population with positive stool exam and with the
      increase of EPG and/or severity of pathological change in the liver and spleen.
      Contrarily, the level of the total IgM and the anti-SEA IgG in serum from fishing
      population in the endemic area was significantly higher than those from non
      endemic area. High level serum antibodies in those stool positives were
      remarkable with the increase of EPG and/or the severity of hepatosplenic
      pathological change. The total IgA increased considerably in the subjects with
      significant pathological change of the liver and spleen. A high total IgG was
      only detected in those stool positives. CONCLUSION: The immune status in
      fishermen with schistosomiasis in the Dongting Lake showed a suppressed cellular
      immunity and a hyper functioning humoral immune response. The imbalance of the
      immunity was related to the increase of the intensity of infection and the
      progress of the hepatosplenic pathology.

PMID- 16300009
TI  - [Impact of chronic schistosomiasis japonica on the protective immunity induced by
      vaccine against hepatitis B virus].
AB  - OBJECTIVE: To study the impact of chronic schistosomiasis on the protective
      immunity induced by vaccine against hepatitis B virus. METHODS: 24 patients with
      chronic or advanced schistosomiasis (experimental group) and 26 healthy
      volunteers (control group) all without hepatitis B virus infection were selected
      for the study. Sera of the subjects in the two groups were collected before
      inoculation and on the 35th day after inoculation with yeast-derived recombinant
      hepatitis B vaccine. The level of anti-Hbs, IL-2 and TNF-alpha in sera was
      examined by ELISA respectively. RESULTS: Anti-Hbs in both groups were negative
      before inoculation, with an average absorbance (A value) of 0.134 and 0.150
      respectively. After inoculation, positive rate of anti-Hbs was 17% (4/24, average
      A value 0.145 ) in experimental group and 92% (24/26, average A value was 1.210)
      in control group. The vaccine against hepatitis B induced significantly higher
      level of anti-Hbs in healthy volunteers compared with that in schistosomiasis
      patients (P < 0.01). The level of IL-2 and TNF-alpha increased in both groups
      after inoculation without significant difference compared with the level before
      inoculation. CONCLUSION: The results suggest that the protective immunity of
      patients with chronic schistosomiasis is deficient to the stimulation of
      hepatitis B virus and it may involve in a higher incidence of hepatitis B among
      schistosomiasis patients.

PMID- 16300011
TI  - [The detection and clinical significance of prealbumin and albumin in serum of
      schistosomiasis patients].

PMID- 16300012
TI  - [Expression of Taenia solium oncosphere 45WB2 gene in Pichia pastoris system].
AB  - OBJECTIVE: To amplify and express the gene from Taenia solium oncosphere in
      Pichia pastoris system. METHODS: Total RNA was extracted from hatched and
      activated oncospheres. A 459bp specific fragment was amplified by RT-PCR. It was
      subcloned into the secreted expression vector pPIC9K, and identified by
      sequencing and then transformed into P. pastoris SMD1168 by electroporation. PCR
      analysis showed that 45WB2 was integrated into the genomic DNA of yeast. The
      recombinants were induced by 1% methanol and the culture supernatant was
      collected and tested by SDS-PAGE and Western blotting. RESULTS: 45WB2 gene was
      expressed successfully in P. pastoris and the product was recognized by human
      positive serum against cysticercosis. CONCLUSION: The recombinant 45WB2 expressed
      in P. pastoris may be used to prevent pigs from the infection of Taenia solium.

PMID- 16300013
TI  - [Pthirus pubis infestation in a couple].

PMID- 16300014
TI  - [Measurement of morphological parameters of Cryptosporidium muris oocysts by
      digital image processing technology].
AB  - OBJECTIVE: To establish and analyze the morphological parameters of the oocysts
      of Cryptosporidium muris for defining their morphological change. METHODS:
      Oocysts were collected from KM mice (immunodepressed by dexamethasone for 10
      days) and examined with modified acid-fast staining. Images of 1 190 oocysts were
      acquired by photograph system. The length, width, perimeter, area and equivalent
      diameter of the oocysts were obtained by computer digital image processing system
      and analyzed by SPSS software (Version 11.0). RESULT: The average length of the
      oocysts was 5.93 microm, ranging from 3.36 microm to 8.51 microm in 95%
      confidence interval of them. The average width was 4.96 microm, ranging from 3.26
      microm to 6.66 microm in 95% confidence interval of them. The average perimeter
      was 18.03 microm and the average area was 16.08 microm2. CONCLUSION: Data
      obtained from the computer system are objective and precise, offering scientific
      foundation for measuring the oocysts and for identifying Cryptosporidium spp.

PMID- 16300015
TI  - [Research progress on molecular biology of Eimeriina oocyst].

PMID- 16300016
TI  - [Research progress of the evaluation methods on the resistance of schistosome to
      praziquantel].

PMID- 16300017
TI  - [Diagnosis and treatment of larva migrans due to Paragonimus westermani: 106
      cases in children].

PMID- 16300018
TI  - [Effect of the culture fluid of Trichinella spiralis on the apoptosis and
      necrosis of human leukaemia K562 cells].

PMID- 16300019
TI  - [Clinical analysis of 32 cases with neurocysticercosis in children].

PMID- 16300020
TI  - [Effect of morphine on the development of Lucilia sericata larvae].

PMID- 16300022
TI  - [An epidemiological investigation on the main parasitic diseases in rural
      residents of Ninxia].

PMID- 16300021
TI  - [Establishment of a dipstick test using soluble adult worm antigen of
      Pagumogonimus skrjabini].

PMID- 16300024
TI  - [Survey on intestinal parasitic infections in students of one school in Henan for
      12 years].

PMID- 16300023
TI  - [Investigation on Paragonimus infection in 6 counties of Fujian Province].

PMID- 16300025
TI  - Avian influenza: frequently asked questions.

PMID- 16300026
TI  - Global measles and rubella laboratory network--update.

PMID- 16300027
TI  - Follow-up care of patients with fully resected colon cancer.

PMID- 16300028
TI  - Nasal irrigation to treat acute bacterial rhinosinusitis.

PMID- 16300029
TI  - Medical homes: the unsung solution for quality health care.

PMID- 16300030
TI  - Excess, shortage, or sufficient physician workforce: how could we know?
AB  - At least three models have been used to project the future physician workforce,
      and each produces different results. No physician workforce predictions can be
      relied on until there is more consideration of and agreement on desired health
      outcomes and what physicians must do to achieve them.

PMID- 16300031
TI  - Psychological interventions for noncardiac chest pain.

PMID- 16300032
TI  - Diagnosis and management of ectopic pregnancy.
AB  - Ectopic pregnancy is a high-risk condition that occurs in 1.9 percent of reported
      pregnancies. The condition is the leading cause of pregnancy-related death in the
      first trimester. If a woman of reproductive age presents with abdominal pain,
      vaginal bleeding, syncope, or hypotension, the physician should perform a
      pregnancy test. If the patient is pregnant, the physician should perform a work
      up to detect possible ectopic or ruptured ectopic pregnancy. Prompt ultrasound
      evaluation is key in diagnosing ectopic pregnancy. Equivocal ultrasound results
      should be combined with quantitative beta subunit of human chorionic gonadotropin
      levels. If a patient has a beta subunit of human chorionic gonadotropin level of
      1,500 mIU per mL or greater, but the transvaginal ultrasonography does not show
      an intrauterine gestational sac, ectopic pregnancy should be suspected.
      Diagnostic uterine curettage may be appropriate in patients who are
      hemodynamically stable and whose beta subunit of human chorionic gonadotropin
      levels are not increasing as expected. Appropriate treatment for patients with
      nonruptured ectopic pregnancy may include expectant management, medical
      management with methotrexate, or surgery. Expectant management is appropriate
      only when beta subunit of human chorionic gonadotropin levels are low and
      declining. Initial levels determine the success of medical treatment. Surgical
      treatment is appropriate if ruptured ectopic pregnancy is suspected and if the
      patient is hemodynamically unstable.

PMID- 16300033
TI  - Information from your family doctor. Ectopic pregnancy: what you should know.

PMID- 16300034
TI  - Detection and evaluation of chronic kidney disease.
AB  - Chronic kidney disease affects approximately 19 million adult Americans, and its
      incidence is increasing rapidly. Diabetes and hypertension are the underlying
      causes in most cases of chronic kidney disease. Evidence suggests that
      progression to kidney failure can be delayed or prevented by controlling blood
      sugar levels and blood pressure and by treating proteinuria. Unfortunately,
      chronic kidney disease often is overlooked in its earliest, most treatable
      stages. Guidelines from the National Kidney Foundation's Kidney Disease Outcomes
      Quality Initiative (KDOQI) recommend estimating glomerular filtration rate and
      screening for albuminuria in patients with risk factors for chronic kidney
      disease, including diabetes, hypertension, systemic illnesses, age greater than
      60 years, and family history of chronic kidney disease. The glomerular filtration
      rate, calculated by using a prediction equation, detects chronic kidney disease
      more accurately than does the serum creatinine level alone; the glomerular
      filtration rate also is used for disease staging. In most clinical situations,
      analysis of random urine samples to determine the albumin-creatinine or protein
      creatinine ratio has replaced analysis of timed urine collections. When chronic
      kidney disease is detected, an attempt should be made to identify and treat the
      specific underlying condition(s). The KDOQI guidelines define major treatment
      goals for all patients with chronic kidney disease. These goals include slowing
      disease progression, detecting and treating complications, and managing
      cardiovascular risk factors. Primary care physicians have an important role in
      detecting chronic kidney disease early, in instituting measures to slow disease
      progression, and in providing timely referral to a nephrologist.

PMID- 16300035
TI  - Information from your family doctor. Chronic kidney disease.

PMID- 16300036
TI  - Management of acute renal failure.
AB  - Acute renal failure is present in 1 to 5 percent of patients at hospital
      admission and affects up to 20 percent of patients in intensive care units. The
      condition has prerenal, intrarenal, and postrenal causes, with prerenal
      conditions accounting for 60 to 70 percent of cases. The cause of acute renal
      failure usually can be identified through an appropriate history, a physical
      examination, and selected laboratory tests. The initial laboratory evaluation
      should include urinalysis, a determination of the fractional excretion of sodium,
      a blood urea nitrogen to creatinine ratio, and a basic metabolic panel.
      Management includes correction of fluid and electrolyte levels; avoidance of
      nephrotoxins; and kidney replacement therapy, when appropriate. Several recent
      studies support the use of acetylcysteine for the prevention of acute renal
      failure in patients undergoing various procedures. The relative risk of serum
      creatinine elevation was 0.11 in patients undergoing radiocontrast-media
      procedures (absolute risk reduction: 19 percent) and 0.33 in patients undergoing
      coronary angiography (absolute risk reduction: 8 percent). In patients pretreated
      with sodium bicarbonate before radiocontrast-media procedures, the relative risk
      of serum creatinine elevation was 0.13 and the absolute risk reduction was 11.9
      percent. Dopamine and diuretics have been shown to be ineffective in ameliorating
      the course of acute renal failure.

PMID- 16300037
TI  - A clinical approach to diagnosing wrist pain.
AB  - A detailed history alone may lead to a specific diagnosis in approximately 70
      percent of patients who have wrist pain. Patients who present with spontaneous
      onset of wrist pain, who have a vague or distant history of trauma, or whose
      activities consist of repetitive loading could be suffering from a carpal bone
      nonunion or from avascular necrosis. The hand and wrist can be palpated to
      localize tenderness to a specific anatomic structure. Special tests can help
      support specific diagnoses (e.g., Finkelstein's test, the grind test, the
      lunotriquetral shear test, McMurray's test, the supination lift test, Watson's
      test). When radiography is indicated, the posterior-anterior and lateral views
      are essential to evaluate the bony architecture and alignment, the width and
      symmetry of the joint spaces, and the soft tissues. When the diagnosis remains
      unclear, or when the clinical course does not improve with conservative measures,
      further imaging modalities are indicated, including ultrasonography, technetium
      bone scan, computed tomography, and magnetic resonance imaging. If all studies
      are negative and clinically significant wrist pain continues, the patient may
      need to be referred to a specialist for further evaluation, which may include
      cineroentgenography, diagnostic arthrography, or arthroscopy.

PMID- 16300038
TI  - Extrapulmonary tuberculosis: an overview.
AB  - In the 1980s, after a steady decline during preceding decades, there was a
      resurgence in the rate of tuberculosis in the United States that coincided with
      the acquired immunodeficiency syndrome epidemic. Disease patterns since have
      changed, with a higher incidence of disseminated and extrapulmonary disease now
      found. Extrapulmonary sites of infection commonly include lymph nodes, pleura,
      and osteoarticular areas, although any organ can be involved. The diagnosis of
      extrapulmonary tuberculosis can be elusive, necessitating a high index of
      suspicion. Physicians should obtain a thorough history focusing on risk behaviors
      for human immunodeficiency virus (HIV) infection and tuberculosis.
      Antituberculous therapy can minimize morbidity and mortality but may need to be
      initiated empirically. A negative smear for acid-fast bacillus, a lack of
      granulomas on histopathology, and failure to culture Mycobacterium tuberculosis
      do not exclude the diagnosis. Novel diagnostic modalities such as adenosine
      deaminase levels and polymerase chain reaction can be useful in certain forms of
      extrapulmonary tuberculosis. In general, the same regimens are used to treat
      pulmonary and extrapulmonary tuberculosis, and responses to antituberculous
      therapy are similar in patients with HIV infection and in those without.
      Treatment duration may need to be extended for central nervous system and
      skeletal tuberculosis, depending on drug resistance, and in patients who have a
      delayed or incomplete response. Adjunctive corticosteroids may be beneficial in
      patients with tuberculous meningitis, tuberculous pericarditis, or miliary
      tuberculosis with refractory hypoxemia.

PMID- 16300039
TI  - Medications for treating alcohol dependence.
AB  - Medications for treating alcohol dependence primarily have been adjunctive
      interventions, and only three medications--disulfiram, naltrexone, and
      acamprosate--are approved for this indication by the U.S. Food and Drug
      Administration. Disulfiram, an aversive agent that has been used for more than 40
      years, has significant adverse effects and compliance difficulties with no clear
      evidence that it increases abstinence rates, decreases relapse rates, or reduces
      cravings. In contrast, naltrexone, an anticraving agent, reduces relapse rates
      and cravings and increases abstinence rates. Acamprosate also reduces relapse
      rates and increases abstinence rates. Serotonergic and anticonvulsant agents
      promise to play more of a role in the treatment of alcohol dependence. Although
      not approved by the U.S. Food and Drug Administration for this indication, the
      anticonvulsant topiramate and several serotonergic agents (e.g., fluoxetine,
      ondansetron) have been shown in recent studies to increase abstinence rates and
      decrease drinking.

PMID- 16300040
TI  - Diagnosing and treating patients with suspected influenza.

PMID- 16300041
TI  - Antiviral agents for pregnant women with genital herpes.

PMID- 16300043
TI  - Information from your family doctor. Tension headaches: what you should know.

PMID- 16300042
TI  - A pregnant patient with dyspnea.

PMID- 16300044
TI  - Information from your family doctor. Migraine headaches: how to deal with the
      pain.

PMID- 16300045
TI  - Information from your family doctor. Cluster headaches: what you should know.

PMID- 16300046
TI  - [Evaluation of the assembling and retention forces of constraint liners for total
      hip replacement].
AB  - Dislocation is a severe complication after total hip replacement which may cause
      revision surgery in some cases. The use of constraint inserts that are coupled to
      the femoral head by a snapping mechanism provides an opportunity for treatment of
      recurrent dislocations. This study was aimed to investigate the assembling and
      retention forces of a specific constraint liner. Using a universal testing
      machine the assembling forces were determined for head sizes of 28 and 32 mm and
      the clinically mostly used as well as the maximum cup size. Subsequently, under
      variation of load direction and pull-out velocity the retention forces were
      investigated. For primary assembly of the head the required compressive forces
      were in a range from 197 N and 283 N depending on head and cup size (each size n
      = 3). Repeated assembly led to a decrease of these forces up to 29%. The
      retention forces always were slightly below the assembling forces, i. e. forces
      to remove the heads from the inserts were between 183 N and 230 N (each size n =
      3). Repeated disconnection caused a decrease of the retention forces up to 16%.
      An increase of load velocity as well as an oblique load direction resulted in an
      enhancement of the retention forces. For all investigated implant sizes the
      retention force for the femoral head was approximately ten-times less than the
      interface strength between the insert and the metal-back. In case of correct
      implant handling the risk of disconnection between the tested constraint insert
      and the corresponding metal-back has not to be considered in clinical practice.

PMID- 16300047
TI  - [Corrosion behaviour, metal release and biocompatibility of implant materials
      coated by TiO2-sol gel chemistry].
AB  - Alloys based on titanium or cobalt have been used as implant materials for
      decades with good success. Because of their natural oxide layer these alloys
      reveal good corrosion behaviour. In contact with physiological solution metal
      release takes place, which can cause inflammation. Coatings can improve the
      corrosion behaviour. In this study Ti6Al4V and Co28Cr6Mo alloys, which are
      frequently used as implant materials, were tested. Polished discs of these alloys
      and polished discs, which were coated with TiO2-layers by sol-gel chemistry, were
      compared regarding their corrosion behaviour and metal ion releasing. The
      releasing of Al, V, Ti, Co, Cr and Mo was quantified by ICP-MS analysis. The TiO2
      coating reduced the release of all ions except of the Al-ion. Both alloys showed
      a deviating kinetic of ion releasing. In addition, cell response (cell vitality,
      cell proliferation, endothelial marker CD31 and actin allocation) of osteoblasts
      and endothelial cells were investigated.

PMID- 16300048
TI  - [Cytokine profile of a human bone marrow cell culture under the influence of UHMW
      PE wear particles].
AB  - There is considerable evidence that orthopaedic wear debris plays a crucial role
      in the pathology of aseptic loosening of joint prostheses. The purpose of the
      present study was to evaluate the influence of ultra-high-molecular-weight
      polyethylene (UHMW-PE) on the cytokine response in a modified in vitro model.
      UHMW-PE particles (psi < 7.5 microm) were suspended in soluble collagen type I
      and subsequently solidified in different concentrations (105,106 and 107
      particles per well) on the bottom of the wells. Human bone marrow cells in a
      concentration of 3 x 106 cells per well were seeded on the collagen-particle
      substrata and maintained for up to 12 days. The cytokine response (IL-1_, IL-6
      and TNF-_) of the cells to the particles were examined by ELISA compared to cells
      on control collagen surfaces without any particles. Assays for viability using
      LDH activity were done immediately. Light and scanning microscopic evaluation
      revealed that the UHMWPE particles, which have built large conglomerates
      (psi7.5_m), were mainly surrounded by the cells and less phagocytosed. The
      results of the cytokine release revealed significant differences in interleukin
      (IL)6, tumor necrosis factor (TNF)- _ and IL-1beta. The cell viability was not
      affected by the UHMW-PE particles. The results demonstrate that the particle
      induced cytokine response by UHMW-PE is mainly by the release of Interleukin 6
      and TNF- _. Moreover the results confirm that the present method is useful to
      evaluate the in vitro effects of UHMW-PE wear particles with direct particle cell
      contact.

PMID- 16300049
TI  - [Evaluation of potential risks of abrasive water jet osteotomy in-vivo].
AB  - Since the 80's the water jet scalpel is an established tool in some surgical
      fields. It is used in particular in visceral surgery for preparation of
      parenchymatous organs. By the addition of biocompatible abrasives, this technique
      is able to effectively machine hard biological tissues. Free defined cutting
      geometries can be realised in a non contact process. Therewith this method has
      crucial advantages compared to conventional osteotomy techniques and gives new
      impulses to the development in endoprosthetics and correction osteotomies of
      hollow bones. In the presented work the new developed abrasive water injection
      jet (AWIJ) was used the first time for in-vivo osteotomies. Aim of this study was
      the detection of potential thrombembolic effects and wash in effects of the
      cutting fluid. Hollow bones of the fore and hind leg of 20 house pigs were
      treated with the new cutting technique. Intraoperative documentation of relevant
      vital parameters was performed by a multi monitoring system. Thrombembolic
      effects during the osteotomy were detected by transthoracic Doppler
      ultrasonography and transesophagale echocardiography. The hollow bones were
      prepared in consideration of the vascularisation's protection especially in
      respect to the venous flow. Thrombembolic effects with temporary haemodynamic
      respectively respiratory consequences could be detected exclusively by using the
      so called "3-component jet", which consists of 90 vol % of air. The usage of an
      abrasive suspension enables the airfree dosing of dry soluable abrasives.
      Thrombembolic effects could not be monitored in this case. Intramedullary fluid
      in-wash effects as well as resulting electrolytic disorders could not be proven.
      For abrasive waterjet osteotomies with 3 component jet a relevant risk of
      thrombembolic effects could be shown. This knowledge has also to be considered
      for abdominal and neurosurgical applications in the future. Due to the usage of
      an abrasive suspension this risk can fully be avoided.

PMID- 16300050
TI  - Effect of an interspinous implant on loads in the lumbar spine.
AB  - Interspinous process implants are increasingly used to treat canal stenoses.
      Little information exists about the effects of implant height and stiffness on
      the biomechanical behavior of the lumbar spine. Therefore, a three-dimensional
      nonlinear finite element model of the osseoligamentous lumbar spine (L1 to L5)
      was created with a slightly degenerated disc at L3/L4. An interspinous implant
      was inserted at that segment. Implants with different heights and stiffnesses
      were studied. The model was loaded with the upper body weight and muscle forces
      to simulate walking and 25 degrees extension. Implant forces are influenced
      strongly by the height and negligibly by the elastic modulus of the implant.
      Intersegmental rotation at implant level is markedly reduced, while intradiscal
      pressure is slightly increased. Implant size and stiffness have only a minor
      effect on intradiscal pressure. The maximum von Mises stress in the vertebral
      arch is strongly increased by the implant.

PMID- 16300051
TI  - Government abandons blanket rules on PCT service provision.

PMID- 16300052
TI  - PCT reconfiguration. First look at the primary care revolution.

PMID- 16300053
TI  - On competing for your medics.

PMID- 16300054
TI  - Data briefing. Cardiac wait times.

PMID- 16300055
TI  - Choice. Shop 'til you drop.
AB  - It is unclear whether the public will embrace choice with enough enthusiasm to
      drive improvement. A series of focus groups have confirmed there is general
      support for choice, but also concern about how patients would get information to
      inform their decisions. Many people would act against one of the main drivers of
      the policy and choose to wait.

PMID- 16300056
TI  - On why PCTs fail clinicians.

PMID- 16300057
TI  - Ambition. Why some people are most likely to succeed.

PMID- 16300058
TI  - Ambition and kids. How to help them succeed.

PMID- 16300059
TI  - Music and the mind.

PMID- 16300060
TI  - A simple method for the direct detection of Salmonella and Escherichia coli
      O157:H7 from raw alfalfa sprouts and spent irrigation water using PCR.
AB  - The U.S. Food and Drug Administration recognizes that raw seed sprouts are an
      important cause of foodborne disease and is now recommending that either spent
      irrigation water or final product be screened for Salmonella and Escherichia coli
      O157:H7 as a means of assuring the safety of product intended for consumption. In
      an effort to streamline such testing efforts, a simple method to preconcentrate
      pathogens from sprouts and spent irrigation water was investigated to facilitate
      the direct (without prior cultural enrichment) detection of pathogens using the
      PCR technique. Alfalfa sprouts and spent irrigation water were seeded with
      Salmonella enterica serovar Typhimurium and E. coli O157:H7 at 10(-1) to 106
      CFU/g or CFU/ml, respectively. Samples were blended (sprouts only) and then
      centrifuged at high speed to sediment the total bacterial population. The
      precipitate was processed for DNA isolation, PCR amplification, and amplicon
      confirmation by Southern hybridization. Mean pathogen recoveries after
      centrifugation ranged from 96 to 99% for both pathogens in both matrices. Using
      primers targeting the invA gene for Salmonella Typhimurium and the stx genes of
      E. coli O157:H7, it was possible to detect both pathogens in alfalfa sprouts at
      seeding concentrations as low as 10 CFU/g. PCR detection limits for both
      pathogens from spent irrigation water were 10(-1) CFU/ml, the equivalent of 100
      CFU/liter of water. Because spent irrigation water is constitutionally simple, it
      is particularly well suited for bacterial concentration by simple centrifugation
      steps. In this study, progress was made toward development of a rapid,
      inexpensive, and sensitive method for the detection of sprout-associated
      pathogens that is relevant to current industrial practices and needs.

PMID- 16300061
TI  - Methods for recovering Escherichia coli O157:H7 from cattle fecal, hide, and
      carcass samples: sensitivity and improvements.
AB  - The Meats Research Unit (MRU) methods, developed by MRU scientists of the U.S.
      Meat Animal Research Center, have been used to study the prevalence of
      Escherichia coli O157:H7 in cattle carcass, hide, and fecal samples. The
      sensitivity of these methods for recovery of injured E. coli O157:H7 cells from
      inoculated and uninoculated samples was determined, and potential improvements to
      these methods were evaluated. When using the conventional MRU methods, 91% of the
      pre-evisceration carcass samples tested positive for E. coli O157:H7 when
      inoculated with 5 to 10 CFU, 100% of hide samples tested positive for E. coli
      O157:H7 when inoculated with 30 to 50 CFU, and 96% of the fecal samples produced
      positive results when inoculated with 300 to 400 CFU per 10 g. The addition of a
      phosphate buffer to the tryptic soy broth enrichment improved recovery of E. coli
      O157:H7 from feces. Using the modified enrichment, 92% of the samples were
      identified as positive when inoculated with 10 to 30 CFU per 10 g. Substituting a
      commercially available wash buffer for the phosphate-buffered saline (PBS) plus
      Tween 20 wash buffer during immunomagnetic separation of hide samples improved
      recovery of the target organism at lower inoculum concentrations. When comparing
      uninoculated samples, substituting a PBS buffer plus a zwitterionic detergent for
      PBS plus Tween 20 also had a positive effect on recovery of E. coli O157:H7 from
      hide samples. Data presented here indicate that the MRU methods are highly
      effective at recovering injured E. coli O157:H7 from fecal, hide, and beef
      carcass samples; however, modifications can be added to increase the sensitivity.

PMID- 16300062
TI  - Belgian surveillance plans to assess changes in Salmonella prevalence in meat at
      different production stages.
AB  - From 1997 to 1999, the prevalence of Salmonella was assessed at different stages
      through the pork, poultry, and beef meat production chains. Different dilutions
      of the initial sample suspension were analyzed to provide a semiquantitative
      evaluation of Salmonella contamination and to determine the most representative
      dilution necessary to detect a reduction in prevalence. An average of 300 samples
      for each type of meat were analyzed. According to Fisher's exact test, the
      dilution to be used to detect a reduction in prevalence was chosen based on an
      initial prevalence of 20 to 26%. Based on this introductory study, a new sampling
      plan representative of the nationwide Belgian meat production process was used
      from 2000 through to 2003. This study confirmed the consistently high rate and
      level of contamination of poultry meat: broiler and layer carcasses were the most
      contaminated samples followed by broiler fillets and poultry meat preparations. A
      constant and significant decrease in Salmonella prevalence was observed for pork
      carcasses, trimmings, and minced meat and for beef minced meat. Less than 3% of
      beef carcasses and trimming samples were positive for Salmonella. The Belgian
      plan, as utilized from 2000 to 2003, was suitable for monitoring of zoonoses
      because the sampling plan was representative of nationwide production processes,
      covered all periods of the year, and was executed by trained samplers and the
      analyses were carried out by recognized laboratories using an identical
      analytical method.

PMID- 16300063
TI  - Use of oligonucleotide array for identification of six foodborne pathogens and
      Pseudomonas aeruginosa grown on selective media.
AB  - Identification of presumptive foodborne pathogens grown on selective media may
      take one to several days and requires a different battery of biochemical tests
      for each microorganism. A molecular identification method was developed in which
      universal primers were used to amplify the 16S to 23S rDNA intergenic spacer of
      target microorganisms, and PCR products were hybridized to a panel of species
      specific oligonucleotides that were immobilized on a nylon membrane. The seven
      target microorganisms were Bacillus cereus, Escherichia coli, Listeria
      monocytogenes, Pseudomonas aeruginosa, Salmonella, Staphylococcus aureus, and
      Vibrio parahaemolyticus. After testing a large collection of target bacteria (29
      to 51 strains) and nontarget bacteria (> 500 strains), the performances
      (sensitivity and specificity) of the oligonucleotide array were as follows: B.
      cereus (100 and 77%), E. coli (100 and 100%), L. monocytogenes (100 and 90%), P.
      aeruginosa (100 and 100%), Salmonella (100 and 100%), S. aureus (100 and 100%),
      and V. parahaemolyticus (100 and 94.2%). Other species in the B. cereus group
      cross-hybridized to the probes used for identification of B. cereus, and positive
      results should be confirmed by additional morphological observation of colonies.
      Listeria innocua cross-reacted with probes used to identify L. monocytogenes, but
      a simple hemolysis test was used to differentiate the two species. Some strains
      of Vibrio harveyi and Vibrio mimicus cross-hybridized with probes used for
      identification of V. parahaemolyticus and caused false-positive reactions. The
      advantage of the array is that a common protocol was used to identify the seven
      target microorganisms and multiple different microorganisms could be
      simultaneously identified on a single array.

PMID- 16300064
TI  - Biofilm formation, extracellular polysaccharide production, and cell-to-cell
      signaling in various Enterobacter sakazakii strains: aspects promoting
      environmental persistence.
AB  - Enterobacter sakazakii is considered an opportunistic pathogen and has been
      implicated in food-associated cases of meningitis or enteritis, especially in
      neonates and infants. The organism has been detected in various types of food and
      in food production units, but so far only powdered infant formula has been linked
      to outbreaks of disease. Survival and persistence in such environments requires
      the ability to adapt to high osmotic potentials and/or dry conditions. Fifty-six
      E. sakazakii strains were evaluated for several features important for
      persistence and survival: (i) biofilm formation and the putative production of
      cellulose as one of the components of the extracellular matrix, (ii) adherence to
      hydrophilic and hydrophobic surfaces, (iii) the production of extracellular
      polysaccharides, and (iv) the ability of E. sakazakii to produce cell-to-cell
      signaling molecules. Pellicle and flock formation was observed in 21 of the
      strains grown in Luria-Bertani broth and in 44 of the strains grown in brain
      heart infusion broth. Calcofluor-stained fibrils, observed microscopically in
      every (fragile or rigid) pellicle, suggested the presence of cellulose as an
      extracellular compound in this type of biofilm. Twelve isolates did not form any
      pellicle or flocks under either condition. Twenty-three of the isolates exhibited
      the potential to adhere to glass surfaces in shaken cultures, and 33 strains
      showed biofilm formation at the air-solid interface of polyvinyl chloride
      microtiter wells. Sixteen isolates adhered to both surfaces. Twenty-four of the
      isolates tested produced a milky, viscous mass, considered as extracellular
      polysaccharide. High-performance liquid chromatography analysis of the
      polysaccharide revealed the presence of glucose, galactose, fucose, and
      glucuronic acid. Thin-layer chromatography analyses performed on ethyl acetate
      extracts of cell-free supernatants of the 56 strains indicated the presence of
      two different types of acylated homoserine lactones (3-oxo-C6-HSL and 3-oxo-C8
      HSL). These findings illustrate the ability of E. sakazakii to produce cell-to
      cell signaling molecules.

PMID- 16300065
TI  - Probiotics down-regulate flaA sigma28 promoter in Campylobacter jejuni.
AB  - Lactobacilli and bifidobacteria are important members of the gastrointestinal
      microflora of humans and animals and are thought to have positive effects on
      human health. Therefore, there is an increasing interest in using these
      microorganisms as probiotics to be incorporated into either fermented dairy
      products or tablets. However, convincing scientific data that support claims of
      their health benefits are scarce. The effect of cell-free extracts of milk
      fermented by 10 probiotic bacteria (five Bifidobacterium strains and five
      Lactobacillus strains) on the expression of the flaA gene of Campylobacter jejuni
      was assessed using a fusion between the flaA sigma28 promoter and a promoterless
      luxCDABE cassette carried on the plasmid pRYluxCDABE, which resulted in strains
      with quantifiable luminescence linked to flaA sigma28 promoter activity. Cell
      free extracts of milk fermented by all of the tested probiotic strains inhibited
      the growth of the C. jejuni and down-regulatedflaA sigma28 promoter activity. Two
      nonprobiotic lactic acid bacterial strains, Lactococcus lactis and Streptococcus
      thermophilus, were less inhibitory.

PMID- 16300066
TI  - Quantifying the robustness of a broth-based Escherichia coli O157:H7 growth model
      in ground beef.
AB  - The robustness of a microbial growth model must be assessed before the model can
      be applied to new food matrices; therefore, a methodology for quantifying
      robustness was developed. A robustness index (RI) was computed as the ratio of
      the standard error of prediction to the standard error of calibration for a given
      model, where the standard error of calibration was defined as the root mean
      square error of the growth model against the data (log CFU per gram versus time)
      used to parameterize the model and the standard error of prediction was defined
      as the root mean square error of the model against an independent data set. This
      technique was used to evaluate the robustness of a broth-based model for aerobic
      growth of Escherichia coli 0157:H7 (in the U.S Department of Agriculture
      Agricultural Research Service Pathogen Modeling Program) in predicting growth in
      ground beef under different conditions. Comparison against previously published
      data (132 data sets with 1,178 total data points) from experiments in ground beef
      at various experimental conditions (4.8 to 45 degrees C and pH 5.5 to 5.9)
      yielded RI values ranging from 0.11 to 2.99. The estimated overall RI was 1.13.
      At temperatures between 15 and 40 degrees C, the RI was close to and smaller than
      1, indicating that the growth model is relatively robust in that temperature
      range. However, the RI also was related (P < 0.05) to temperature. By quantifying
      the predictive accuracy relative to the expected accuracy, the RI could be a
      useful tool for comparing various models under different conditions.

PMID- 16300067
TI  - Quantifying the robustness of a broth-based model for predicting Listeria
      monocytogenes growth in meat and poultry products.
AB  - Given the importance of Listeria monocytogenes as a risk factor in meat and
      poultry products, there is a need to evaluate the relative robustness of
      predictive growth models applied to meat products. The U.S. Department of
      Agriculture-Agricultural Research Service Pathogen Modeling Program is a tool
      widely used by the food industry to estimate pathogen growth, survival, and
      inactivation in food. However, the robustness of the Pathogen Modeling Program
      broth-based L. monocytogenes growth model in meat and poultry application has
      not, to our knowledge, been specifically evaluated. In the present study, this
      model was evaluated against independent data in terms of predicted microbial
      counts and covered a range of conditions inside and outside the original model
      domain. The robustness index was calculated as the ratio of the standard error of
      prediction (root mean square error of the model against an independent data set
      not used to create the model) to the standard error of calibration (root mean
      square error of the model against the data set used to create the model). Inside
      the calibration domain of the Pathogen Modeling Program, the best robustness
      index for application to meat products was 0.37; the worst was 3.96. Outside the
      domain, the best robustness index was 0.40, and the worst was 1.22. Product type
      influenced the robustness index values (P < 0.01). In general, the results
      indicated that broth-based predictive models should be validated against
      independent data in the domain of interest; otherwise, significant predictive
      errors can occur.

PMID- 16300068
TI  - Listeria monocytogenes inhibition by whey protein films and coatings
      incorporating lysozyme.
AB  - The effects of whey protein isolate (WPI) films and coatings incorporating
      lysozyme (LZ) on the inhibition of Listeria monocytogenes both in and on
      microbial media, as well as on cold-smoked salmon, were studied. The
      antimicrobial effects of LZ were examined using various growth media by turbidity
      and plate counting tests. Disc-covering and disc-surface-spreading tests were
      also used to evaluate the effects of WPI films incorporating LZ. Smoked salmon
      was used as a model food to test the antimicrobial effects of WPI coatings
      incorporating LZ, both initially and during storage at 4 and 10 degrees C for 35
      days. Tensile properties (elastic modulus, tensile strength, and percentage of
      elongation), oxygen permeability, and color (Hunter L, a, and b) of WPI films
      with and without LZ were also compared. LZ inhibited L. monocytogenes in broth
      and on agar media. The number of cells surviving after LZ treatments depended on
      the type of media. WPI films incorporating 204 mg of LZ per g of film (dry basis)
      inhibited the growth of a preparation of 4.4 log CFU/cm2 L. monocytogenes. WPI
      coatings prepared with 25 mg of LZ per g of coating solution initially
      inactivated more than 2.4, 4.5, and 3.0 log CFU/g of L. monocytogenes, total
      aerobes, and yeasts and molds in smoked salmon samples, respectively. The WPI
      coatings incorporating LZ efficiently retarded the growth of L. monocytogenes at
      both 4 and 10 degrees C. The anti-L. monocytogenes effect of LZ-WPI coating was
      more noticeable when the coating was applied before inoculation than when the
      coating was applied after inoculation. Significantly higher elastic modulus
      values and lower percentage of elongation and oxygen permeability values were
      measured with the WPI films incorporating LZ than with the plain WPI films.

PMID- 16300069
TI  - Application of predictive models to estimate Listeria monocytogenes growth on
      frankfurters treated with organic acid salts.
AB  - Organic acid salts including sodium lactate, sodium diacetate, potassium
      benzoate, potassium sorbate, and their combinations were assessed as potential
      inhibitors of Listeria monocytogenes growth on frankfurters. Predictive models
      for L. monocytogenes growth on frankfurters treated with these salts were
      compared to select a proper L. monocytogenes growth curve model under these
      conditions. Sigmoidal equations, including logistic and Gompertz equations, are
      widely used to describe bacterial growth. In this study, the reparameterized
      Gompertz model provided a better fit to the L. monocytogenes growth data compared
      with the other models that were included in this study. Rather than a fixed value
      for the maximum number of organisms, the reparameterized Gompertz model allows
      this quantity to be estimated from the data to determine the effect, if any, of
      the treatments on maximum population density. This information is expected to
      improve practical methodology for hazard characterization of microbial pathogens
      on ready-to-eat meat products.

PMID- 16300070
TI  - Power ultrasound treatment of Listeria monocytogenes in apple cider.
AB  - Inactivation experiments with Listeria monocytogenes 10403S, an ultrasound
      resistant strain, were conducted at sublethal (20, 30, and 40 degrees C) and
      lethal (50, 55, and 60 degrees C) temperatures in saline solution (pH 7.0),
      acidified saline solution (pH 3.4), and apple cider (pH 3.4) with and without
      application of ultrasound (20 kHz, 457 mW.ml(-l)). The survival of recoverable L.
      monocytogenes 10403S in apple cider was evaluated, and the effects of
      temperature, ultrasound, pH, and food matrix on inactivation were studied.
      Application of ultrasound increased the inactivation rate at both sublethal and
      lethal temperatures. Additional death of L. monocytogenes 10403S was due to low
      acidity at the lethal temperatures. The reduction in surviving L. monocytogenes
      10403S followed first order kinetics at sublethal temperatures, but at lethal
      temperatures, a two-section linear model described the inactivation behavior. The
      bactericidal effect of thermosonication was additive in apple cider. The survival
      tests of L. monocytogenes 10403S in apple cider indicated the possibility of
      using a mild treatment condition in combination with ultrasound to achieve a 5
      log reduction in number of listerial cells.

PMID- 16300071
TI  - Starter cultures and high-pressure processing to improve the hygiene and safety
      of slightly fermented sausages.
AB  - The effectiveness of selected starter cultures and high hydrostatic pressure
      after ripening was evaluated to improve the safety and quality of slightly
      fermented sausages. Inhibition of common foodborne pathogens, spoilage bacteria,
      and biogenic amine content was studied. Random amplification of polymorphic DNA
      and plasmid profiles were used to monitor the competitiveness of the starter
      cultures during fermentation and ripening. Lactobacillus sakei CTC6626 and
      Staphylococcus xylosus CTC6013 dominated L. sakei CTC6469 and S. xylosus CTC6169
      independently of the product assayed. Starter cultures were able to control the
      growth of Listeria monocytogenes, Enterobacteriaceae, Enterococcus, and the
      biogenic amine content. A pH decrease below 5.3 at the seventh day of
      fermentation was crucial. Salmonella spp. counts decreased significantly during
      ripening independently of the use of starter culture and product. High
      hydrostatic pressure treatment was necessary to ensure absence of Salmonella spp.
      in final products.

PMID- 16300072
TI  - Efficacy of cetylpyridinium chloride against Listeria monocytogenes and its
      influence on color and texture of cooked roast beef.
AB  - Sliced (cut) and exterior (intact) surfaces of restructured cooked roast beef
      were inoculated with Listeria monocytogenes, treated with cetylpyridinium
      chloride (CPC; immersion in 500 ml of 1% solution for 1 min), individually vacuum
      packaged, and stored for 42 days at 0 or 4 degrees C. Noninoculated samples were
      similarly treated, packaged, and stored to determine effects on quality (color
      and firmness) and on naturally occurring bacterial populations, including aerobic
      plate counts and lactic acid bacteria. Immediately after CPC treatment,
      regardless of inoculation level, L. monocytogenes populations were reduced (P =
      0.05) by about 2 log CFU/cm2 on sliced surfaces and by about 4 log CFU/cm2 on
      exterior surfaces. Throughout 42 days of refrigerated storage (at both 0 and 4
      degrees C), L. monocytogenes populations on CPC-treated samples remained lower (P
      = 0.05) than those of nontreated samples for both surface types. After 42 days of
      storage at both 0 and 4 degrees C, aerobic plate count and lactic acid bacteria
      populations of treated samples were 1 to 1.5 log CFU/cm2 lower (P = 0.05) than
      those of nontreated samples for both surface types. CPC treatment resulted in
      negligible effects (P > 0.05) on the color (L*, a*, and b* values) of exterior
      and sliced roast beef surfaces during storage. For both sliced and exterior
      surfaces, CPC-treated samples were generally less firm than nontreated samples.
      CPC treatment effectively reduced L. monocytogenes populations on roast beef
      surfaces and resulted in relatively minor impacts on color and texture
      attributes. CPC treatment, especially when applied to products prior to slicing,
      may serve as an effective antimicrobial intervention for ready-to-eat meat
      products.

PMID- 16300073
TI  - Listeria monocytogenes survival in refrigerator dill pickles.
AB  - Listeria monocytogenes can survive and grow in refrigerated foods with pH values
      of approximately 4.0 to 5.0 and salt concentrations of 3 to 4%. Home-fermented
      refrigerator dill pickles fit this description. Contamination of this product
      with L. monocytogenes could cause serious problems because these items are not
      heated prior to consumption. L. monocytogenes survival and growth patterns were
      investigated in refrigerator dill pickles at 1.3, 3.8, and 7.6% salt
      concentrations. Pickling cucumbers were dipped into an inoculum of L.
      monocytogenes, brine mixtures were added, and cucumbers were held at room
      temperature for 1 week and then refrigerated for up to 3 months. The pH, NaCl
      percentage, titratable acidity percentage, and total populations of Listeria and
      aerobic, psychrotrophic, and lactic acid bacteria were measured at the addition
      of brine, after 2, 4, and 7 days of storage at room temperature, and then weekly
      during refrigerated storage. The initial Listeria population was 5.4 to 5.6 log
      CFU/cm2 on cucumber surfaces and 3.9 to 4.6 log CFU/g internally. There was an
      approximate 0.3- to 1-log increase during room temperature fermentation followed
      by a population decline during refrigerator storage, with a greater decrease in
      the brines with the highest NaCl concentration. Up to 49 days, the internal
      tissue of pickles with 1.3, 3.8, or 7.6% salt concentrations were presumptively
      positive for L. monocytogenes by the enrichment method, and at 91 days the
      surfaces of such pickles were still positive for L. monocytogenes. Populations of
      total aerobes and lactic acid bacteria increased during room temperature storage
      and decreased gradually during refrigerated storage.

PMID- 16300074
TI  - Thermal resistance of spores from virulent strains of Bacillus anthracis and
      potential surrogates.
AB  - The objective of this study was to determine the thermal resistance of spores of
      Bacillus anthracis and potential surrogates. The heat resistance of spores
      suspended in buffer (pH 7.0 or 4.5), milk, or orange juice was determined at 70,
      80, and 90 degrees C. D-values for B. anthracis strains Sterne, Vollum, and
      Pasteur ranged from < 1 min at 90 degrees C to approximately 200 min at 70
      degrees C and were lower under acidic than under neutral conditions. The D-values
      for B. anthracis spores fell within the range obtained for spores from eight
      strains of Bacillus cereus, Bacillus thuringiensis, Bacillus mycoides, and
      Bacillus subtilis. However, there were significant differences (P < 0.001) among
      the D-values of the strains. The z-values in pH 7.0 buffer and milk averaged
      approximately 10.5 degrees C and were not significantly different among strains
      (P < 0.05). The z-values in pH 4.5 buffer and orange juice averaged 12.9 and 13.9
      degrees C, respectively, significantly (P < 0.05) higher than those obtained in
      milk or in pH 7.0 buffer. The significance of this difference was driven by large
      differences among a few strains. The z-values for B. anthracis strain Pasteur
      were twice as high in the acid media than in the neutral media. This study
      confirms that B. anthracis spores are not unusually heat resistant and that
      spores from validated Bacillus species are appropriate surrogates for thermal
      resistance studies.

PMID- 16300075
TI  - Impact of commercial processing on the microbiology of shell eggs.
AB  - Shell egg microbiology has been studied extensively, but little information is
      available on how modern U.S. processing conditions impact microbial populations.
      As regulations are being drafted for the industry, such information can be
      important for determining processing steps critical to product safety. Five
      different shell egg surface microbial populations (aerobic bacteria, yeasts and
      molds, Enterobacteriaceae, Escherichia coli, and Salmonella) were monitored at 12
      points along the processing line (accumulator, prewash rinse, washer 1, washer 2,
      sanitizer, dryer, oiler, scales, two packer head lanes, rewash entrance, and
      rewash exit). Three commercial facilities were each visited three times, a total
      of 990 eggs were sampled, and 5,220 microbiological samples were subsequently
      analyzed. Although variations existed in concentrations of microorganisms
      recovered from each plant, the patterns of fluctuation for each population were
      similar at each plant. On average, aerobes, yeasts and molds, Enterobacteriaceae,
      and E. coli prevalence were reduced by 30, 20, 50, and 30%, respectively, by the
      end of processing. The microbial concentrations (log CFU per milliliter) in the
      egg rinse collected from packer head lanes were decreased by 3.3, 1.3, 1.3, and
      0.5, respectively, when compared with those of rinses collected from eggs at the
      accumulator. Salmonella was recovered from 0 to 48% of pooled samples in the
      three repetitions. Higher concentrations of Salmonella were recovered from
      preprocessed than from in-process or ready-to-pack eggs. These data indicate that
      current commercial practices decrease microbial contamination of egg shell
      surfaces.

PMID- 16300076
TI  - Minimum leak size determination, under laboratory and commercial conditions, for
      bacterial entry into polymeric trays used for shelf-stable food packaging.
AB  - This study sought to determine the minimum leak size for entry of Enterobacter
      aerogenes under laboratory conditions, and normal flora under commercial
      conditions, into tryptic soy broth with yeast extract (TSBYE), homestyle chicken,
      and beef enchilada packaged in 355-ml polyethylene terephthalate/ethylene vinyl
      alcohol/polypropylene trays. Channel leaks (diameters of 50 to 200 microm) were
      made across the sealing area of the trays. Pinholes (diameters of 5 to 50 microm)
      were made by imbedding laser-drilled metal and plastic disks into the tray lids.
      For the laboratory simulation, all trays were submerged and agitated for 30 min
      at 25 degrees C in phosphate-buffered saline that contained 10(7) CFU/ml of E.
      aerogenes. Under commercial conditions, trays with channel leaks were processed
      in retorts to achieve commercial sterility. All trays were subsequently incubated
      at 37 degrees C for 2 weeks, and their contents plated onto eosin-methylene blue
      agar (for laboratory simulation) to enumerate E. aerogenes and brain heart
      infusion agar (for commercial conditions) to determine the presence of any
      bacteria. Under laboratory conditions, minimum pinhole sizes for E. aerogenes
      entry approximated 5 microm (TSBYE, metal disks; homestyle chicken, plastic
      disks), 20 microm (beef, plastic disks), and 30 microm (beef, metal disks). The
      minimum channel leak sizes for entry of E. aerogenes approximated 10 microm
      (TSBYE), 70 microm (chicken), and 200 microm (beef enchilada). Under commercial
      conditions, the minimum channel leak size for bacterial entry approximated 40
      microm (TSBYE), 50 microm (homestyle chicken), and more than 200 microm (beef).
      Results showed that E. aerogenes can enter pinholes as small as 5 microm under a
      worst-case scenario. This information can be used to set pass and fail parameters
      for leak detection devices.

PMID- 16300077
TI  - Consequences of the development of nisin-resistant Listeria monocytogenes in
      fermented dairy products.
AB  - Wild Listeria isolates representing serovars found in artisanal cheeses
      commercialized in Asturias (northern Spain) were assessed for their
      susceptibility to several bacteriocins. Pediocin PA-1 was the most active
      bacteriocin followed by enterocin AS-48, nisin, and plantaricin C. However, some
      Listeria monocytogenes and Listeria innocua strains were already highly resistant
      to PA-1. Among the wild L. monocytogenes populations, the frequency of
      development of nisin resistance ranged from 10(-6) up to 10(-3), depending on the
      strain. Highly stable mutants with increased nisin resistance (two- to fourfold)
      were isolated and tested for potential cross-resistance to lysozyme, EDTA, and
      various NaCl concentrations and pH values. All mutants were cross-resistant to
      lysozyme but sensitive to EDTA. In contrast, no clear correlation could be
      established between nisin resistance and an altered susceptibility to NaCl or pH
      changes. Nisin-resistant variants were able to survive and even to multiply in
      milk fermented by a nisin-producing Lactococcus, but the growth of the wild-type
      strain was inhibited. The different phenotypes evaluated in this study are
      indicative of the unpredictability of the consequences of the development of
      nisin resistance in a dairy environment. This resistance should be considered
      when making a risk assessment of the long-term use of nisin to control L.
      monocytogenes.

PMID- 16300078
TI  - Temperature and treatment time influence high hydrostatic pressure inactivation
      of feline calicivirus, a norovirus surrogate.
AB  - Interest in high hydrostatic pressure processing as a nonthermal pasteurization
      process for foods continues to increase. Feline calicivirus (FCV), a propagable
      virus that is genetically related to the nonpropagable human noroviruses, was
      used for detailed evaluation of the high pressure processing parameters necessary
      for virus inactivation. Pressure inactivation curves of FCV strain KCD in
      Dulbecco's modified Eagle medium with 10% fetal bovine serum were obtained at 200
      and 250 MPa as a function of time at room temperature. Pressure inactivation
      curves at 200 and 250 MPa also were determined as a function of temperature
      ranging from --10 to 50 degrees C at treatment times of 4 and 2 min,
      respectively. Tailing was observed for inactivation as a function of treatment
      time, indicating that the linear model was not adequate for describing these
      curves. The two nonlinear models, the log logistic and Weibull functions,
      consistently produced better fit to inactivation curves than did the linear
      model. The mean square errors were 0.381 for the log logistic model, 0.425 for
      the Weibull model, and 1.546 for the linear model. For inactivation as a function
      of temperature, FCV was most resistant to pressure at 20 degrees C. Temperatures
      above and below 20 degrees C significantly increased pressure inactivation of
      FCV. A 4-min treatment of 200 MPa at --10 and 50 degrees C reduced the titer of
      FCV by 5.0 and 4.0 log units, respectively; whereas at 20 degrees C the same
      treatment only reduced the titer by 0.3 log units. These novel results point to
      the potential for using temperatures above and particularly below room
      temperature to lower the pressure needed to cause the desired level of virus
      inactivation.

PMID- 16300079
TI  - Ready-to-eat shrimp as an international vehicle of antibiotic-resistant bacteria.
AB  - The occurrence of antibiotic-resistant bacteria in foods of animal origin is a
      potential health threat because resistance can be transferred among bacteria, and
      antibiotic-resistant pathogens may not respond to antibiotic treatments. Thirteen
      brands of ready-to-eat shrimp representing four countries of origin were obtained
      from local grocery stores. Total heterotrophic plate counts were determined, and
      antibiotic-resistant bacteria were isolated. Total heterotrophic colony counts
      ranged from 3.3 to 5.6 log CFU/g, which was within approved quality limits. A
      total of 1,564 isolates representing 162 bacterial species were recovered during
      screening of resistance to 10 antibiotics: ampicillin, ceftriaxone,
      chloramphenicol, clindamycin, erythromycin, nalidixic acid, streptomycin,
      tetracycline, trimethoprim, and vancomycin. Six hundred fifty-seven (42%) of the
      isolates and 131 (81%) of the species had acquired resistance to antibiotics.
      Numerous resistant human pathogens were isolated, including Escherichia coli,
      Enterococcus spp., Salmonella, Shigella flexneri, Staphylococcus spp., and Vibrio
      spp. Nonresistant Yersinia spp. also were isolated. Ready-to-eat shrimp is sold
      with instructions to thaw the product before serving, which may result in
      consumer exposure to antibiotic-resistant bacteria. Widespread trade of this
      product provides an avenue for international dissemination of antibiotic
      resistant pathogens.

PMID- 16300080
TI  - Prevalence and antimicrobial resistance of Campylobacter in antimicrobial-free
      and conventional pig production systems.
AB  - The objectives of this study were to determine and compare the prevalence and
      antimicrobial resistance of Campylobacter species in swine reared in conventional
      and antimicrobial-free (ABF) production systems. Campylobacter coli was the
      predominant species, with 1,459 isolates (99%) in the study. We found
      significantly higher prevalence of C. coli on the ABF farms (77.3%) than on the
      conventional farms (27.6%) among pigs at the nursery stage (P < 0.001). At
      slaughter, we found significantly higher prevalence at the postevisceration than
      at the preevisceration stage (P < 0.001) in both production systems. The 1,459 C.
      coli isolates were tested with the agar dilution method for their susceptibility
      to six antimicrobials: chloramphenicol, ciprofloxacin, erythromycin, gentamicin,
      nalidixic acid, and tetracycline. Resistance was most prevalent against
      tetracycline (66.2% of isolates) followed by erythromycin (53.6% of isolates).
      Frequency of resistance to these two antimicrobials was significantly higher
      among conventional herds (83.4% for tetracycline and 77% for erythromycin) than
      among ABF herds (56.2% for tetracycline and 34.5% for erythromycin). Resistance
      to ciprofloxacin at the MIC (> 4 mg/liter) was also found on farms in both
      systems. Multidrug-resistant C. coli strains were detected in both the
      conventional (7%) and ABF (4%) herds. This is the first report of ciprofloxacin
      resistant strains of C. coli in ABF pigs in the United States. These findings
      highlight the high prevalence of antimicrobial-resistant C. coli in both
      conventional and ABF pig production systems and have significant implications for
      the persistence of antimicrobial-resistant Campylobacter in the pig production
      environment regardless of levels of antimicrobial use.

PMID- 16300081
TI  - Antibiotic resistance and hypermutability of Escherichia coli O157 from feedlot
      cattle treated with growth-promoting agents.
AB  - In a longitudinal study (165 days), we investigated the effect of growth
      promoting agents (monensin and trenbolone acetate-estradiol) and an antibiotic
      (oxytetracycline) on the incidence in feedlot steers of Escherichia coli O157,
      including antibiotic-resistant and hypermutable isolates. Eighty steers in 16
      pens were treated with eight combinations of promoters, and each treatment was
      duplicated. Fecal samples were collected at nine different sampling times for
      detection of E. coli O157. Overall, 50 E. coli O157 isolates were detected in
      treated animals, and none were found in untreated animals. Compared with
      untreated controls, there was a significant association between the utilization
      of growth-promoting agents or antibiotics and the shedding of E. coli O157 at day
      137 (P = 0.03), when a prevalence peak was observed and 50% of the isolates were
      detected. Multiplex PCR assays were conducted for some virulence genes. PCR
      results indicated that all except one isolate possessed at least the Shiga toxin
      gene stx2. MICs for 12 antibiotics were determined, and eight oxytetracycline
      resistant E. coli O157 strains were identified. Antibiotic-resistant strains were
      considered a distinct subpopulation of E. coli O157 by pulsed-field gel
      electrophoresis typing. Seven of these antibiotic-resistant strains were isolated
      early in the study (on or before day 25), and among them two were also
      hypermutable as determined by rifampin mutation frequencies. The proportion of
      hypermutable strains among E. coli O157 isolates remained relatively constant
      throughout the study period. These results indicate that the use of growth
      promoting agents and antibiotics in beef production may increase the risk of
      environmental contamination by E. coli O157.

PMID- 16300082
TI  - Conventional and real-time PCR-based approaches for molecular detection and
      quantitation of bovine species material in edible gelatin.
AB  - The majority of edible gelatin in Europe is derived from pigskin, but a
      significant portion is extracted from bovine tissue. Because of the bovine
      spongiform encephalopathy crisis, consumers might be concerned about the gelatin
      used in various products. To assure consumers of the quality and safety of edible
      gelatin, European Union directive 1999/724/EC described general guidelines for
      gelatin production, including requirements for documentary proof confirming that
      raw materials are from animals fit for human consumption. Analytical methods to
      confirm gelatin documentation or raw material animal species source in the
      finished product are lacking. In this study, several published species-specific
      PCR systems were evaluated as potential molecular methods for determining the
      origin of the raw material used in making gelatin. A recently validated bovine
      species-specific PCR primer set targeting the ATPase 8 subunit gene in bovine
      mitochondrial DNA was suitable for detection of bovine material in gelatin. This
      PCR primer set was optimized using conventional and real-time PCR approaches. An
      evaluation of these two PCR methods confirmed the high specificity for the
      adopted primer set in various gelatin matrices of known origin. The inclusion of
      bovine gelatin in pork or fish gelatin can be detected at 0.1 to 0.001%. These
      PCR assays are potential molecular detection tools that can be used to routinely
      detect bovine gelatin either alone or as an inclusion in gelatin made from other
      species.

PMID- 16300083
TI  - ATP bioluminescence assay for estimation of microbial populations of fresh-cut
      melon.
AB  - Estimation of microbial numbers in foods by conventional microbiological
      techniques takes days, so there is a need for faster methods that can give
      results in minutes. Research was undertaken to investigate the use of
      bioluminescent ATP determination and a firefly luciferase assay to estimate the
      initial population of aerobic mesophilic bacteria on fresh-cut melons immediately
      after preparation and during storage at 5 or 15 degrees C for up to 12 days.
      Populations of aerobic mesophilic bacteria on fresh-cut cantaloupe prepared
      immediately from unsanitized whole melons averaged 3.42 log CFU/g, corresponding
      to an ATP value of 5.40 log fg/g. Populations for fresh-cut honeydew prepared
      from unsanitized whole melon averaged 1.97 log CFU/g, corresponding an ATP value
      of 3.94 log fg/g. Fresh-cut pieces prepared from cantaloupe or honeydew melons
      sanitized with either chlorine (200 ppm free chlorine) or hydrogen peroxide
      (2.5%) had similar ATP values: 3.1 log fg/g (corresponding to bacterial counts
      1.7 log CFU/g) for cantaloupes and 2.6 log fg/g (corresponding to bacterial
      counts of 0.48 CFU/g) for fresh-cut honeydew. Positive linear correlations for
      ATP concentrations and microbial populations were found for fresh-cut cantaloupe
      (R2 = 0.99) and honeydew R2 = 0.95) during storage at 5 degrees C for up to 12
      days. ATP values in fresh-cut melons inoculated with either aerobic mesophilic
      bacteria or yeast and mold were significantly higher (P < 0.05) than control
      values and parallel total plate counts on plate count agar. Results of this study
      indicate that the bioluminescent ATP assay can be used to monitor total microbial
      populations on fresh-cut melon after preparation and during storage for quality
      control purposes to establish specific sell-by or consume-by dates.

PMID- 16300084
TI  - Biogenic amine index for freshness evaluation in iced Mediterranean hake
      (Merluccius merluccius).
AB  - Biogenic amine accumulation was studied during the ice storage of Mediterranean
      hake. Sensory analysis and counts of Shewanella, Pseudomonas, enterobacteria,
      psychrotrophic, and mesophilic bacteria provided complementary information on
      hake spoilage. Putrescine and cadaverine were the main amines accumulated,
      whereas histamine and tyramine were minor amines but had qualitative interest
      from the hygienic point of view. Although all biogenic amines were less abundant
      than in pelagic fish, they may also be used as indicators of freshness and/or
      spoilage in hake. Cadaverine was the amine best correlated with Shewanella, which
      was the specific spoilage organism. Therefore, cadaverine may be regarded as the
      specific spoilage biogenic amine for hake stored at chilling temperatures.
      However, the biogenic amine index, which considers cadaverine, putrescine,
      histamine, and tyramine, has several advantages as an indicator of hake quality.
      Taking into account sensory data, an acceptability limit of the biogenic amine
      index could be established in 15 to 20 microg/g.

PMID- 16300085
TI  - A training course on food hygiene for butchers: measuring its effectiveness
      through microbiological analysis and the use of an inspection checklist.
AB  - The effectiveness of food hygiene training for a group of retail butchers was
      evaluated with the aim of verifying whether the butchers modified their behavior
      in the light of knowledge gained and whether their acquired knowledge or behavior
      change was sustained over a period of time. Microbiological analysis (enumeration
      of mesophilic and coliform bacteria and Escherichia coli) of a raw semiprocessed
      product (stuffed rolled beef) was conducted, and an inspection checklist was
      issued before the training course (T0). Initial results were later compared with
      results obtained 1 month (T1) and 6 months (T6) after the training. The checklist
      comprised 89 items classified into five categories: A, approved suppliers and
      product reception; B, storage conditions and temperature control; C, flow
      process, food handling procedures, and conditions of the window display unit; D,
      facility design and proper cleaning and sanitizing of equipment, utensils, and
      work surfaces; and E, pest control system, water supply control, and garbage
      disposal. The inspection results were recorded as "yes" or "no" for each item.
      Compliance with food safety procedures was recorded as the percentage of "yes"
      answers. The bacterial counts were significantly higher at T0. At T6, there was
      no significant increase in bacterial counts. There was a significant improvement
      in food safety practices at T1 and T6 compared with T0 for all categories. When
      comparing T0 and T1, the largest increases in the compliance scores were seen
      within categories C and D. No significant decrease in scores for compliance with
      food safety practices was observed at T6. Supervision and refresher activities
      may be necessary to maintain behavioral changes for a longer period of time.

PMID- 16300086
TI  - Effects of oxidative compounds on thermotolerance in escherichia coli O157:H7
      strains EO139 and 380-94.
AB  - An oxidative complex composed of ferric iron chloride hexahydrate, ADP, and
      ascorbic acid can generate hydrogen peroxide and hydroxyl radicals in
      fibroblasts. These compounds are naturally found in meat and meat-based products
      and may elicit oxidative stress on Escherichia coli O157:H7, thus conferring
      thermotolerance to the bacterium due to the phenomenon of the global stress
      response. The effect of the levels of the oxidative complex on the
      thermotolerance of E. coli O157:H7 was investigated. Cultures of E. coli O157:H7
      strains EO139 and 380-94 were mixed in three different concentrations (10:10: 40,
      15:15:60, and 20:20:80 microM) of the oxidative complex (iron III chloride, ADP,
      and ascorbic acid, respectively). The samples were inserted into capillary tubes
      and heated in a circulating water bath at 59 and 60 degrees C for EO139 and 380
      94, respectively. Tubes were removed at intervals of 5 min for up to 1 h and
      contents spirally plated on plate count agar that was incubated for 48 h at 37
      degrees C. The thermotolerance of both E. coli O157:H7 strains EO139 and 380-94
      was influenced by the concentrations of the oxidative complex. The ratio of
      10:10:40 microM enhanced thermotolerance of EO139 and 390-94 at 59 and 60 degrees
      C, respectively. However, exposure to the ratios of 15:15:60 and 20:20:80 microM
      rendered the pathogen more sensitive to the lethal effect and did not enhance the
      thermotolerance of the cells. The significance of this study is twofold. This
      experiment proves that oxidative stress can enhance thermotolerance of bacterial
      cells induced by an oxidative complex if only in a specific ratio and
      concentration. It is possible to speculate that if the chemical compounds are
      present in this ratio in meats, they may enhance the thermal resistance of E.
      coli O157:H7 and make the bacteria more difficult to eliminate, thus increasing
      the risk of foodborne illness in consumers.

PMID- 16300087
TI  - Attachment strength to pork skin and resistance to quaternary ammonium salt and
      heat of Escherichia coli isolates recovered from a pork slaughter line.
AB  - The aim of this study was to determine whether the attachment strength to pork
      skin, quaternary ammonium salt resistance, and thermal inactivation kinetics (at
      65 degrees C) of a range of Escherichia coli isolates could be correlated with
      their temporal stability (persistence) within a pork slaughter line. The genetic
      lineage of the E. coli isolates was determined using enterobacterial repetitive
      intergenic consensus-PCR. The genotypes were divided into transient and endemic
      populations based on the number of times they were recovered within and across
      sampling visits made to a pork slaughterhouse. No significant variation in the D
      value at 65 degrees C (0.27 to 0.51 min) was observed among the genotypes tested.
      However, differences in D-values were found for 100 ppm quaternary ammonium salt
      (3.0 to 6.0 min). All of the E. coli genotypes attached strongly to pork skin,
      and a high proportion of cells were irreversibly bound (39 to 42% of the initial
      inoculum). However, variation among genotypes was found with respect to loose
      attachment (21 to 33% of inoculated cells). No correlation between persistence of
      E. coli genotypes within the slaughter line and attachment strength or quaternary
      ammonium salt resistance was found. Variation in either physiological attribute
      could not be predicted based on genetic lineage. Additional or alternative
      factors may contribute to the ability of E. coli populations to become endemic
      within pork processing facilities. More studies should be conducted to elucidate
      the underlying factors that promote the formation of endemic populations of E.
      coli and other enteric bacteria (e.g., Salmonella) within slaughter lines.

PMID- 16300088
TI  - Salmonella prevalence in free-range and certified organic chickens.
AB  - Many consumers assume that broiler chickens grownunder traditional commercial
      conditions will have more Salmonella than free-range or organic chickens, which
      usually are less crowded, have access to outside spaces during grow out, and are
      fed special diets. Despite these perceptions, there is a lack of published
      information about the microbiological status of free-range and organic chickens.
      A total of 135 processed free-range chickens from four different commercial free
      range chicken producers were sampled in 14 different lots for the presence of
      Salmonella. Overall, 9 (64%) of 14 lots and 42 (31%) of 135 of the carcasses were
      positive for Salmonella. No Salmonella were detected in 5 of the 14 lots, and in
      one lot 100% of the chickens were positive for Salmonella. An additional 53 all
      natural (no meat or poultry meal or antibiotics in the feed) processed chickens
      from eight lots were tested; 25% ofthe individual chickens from 37% of these lots
      tested positive for Salmonella. Three lots of chickens from a single organicfree
      range producer were tested, and all three of the lots and 60% of the individual
      chickens were positive for Salmonella.The U.S. Department of Agriculture Food
      Safety and Inspection Service reported that commercial chickens processed from
      2000 to 2003 had a Salmonella prevalence rate of 9.1 to 12.8%. Consumers should
      not assume that free-range or organicconditions will have anything to do with the
      Salmonella status of the chicken.

PMID- 16300089
TI  - Expression of major cold shock proteins and genes by Yersinia enterocolitica in
      synthetic medium and foods.
AB  - Yersinia enterocolitica is a psychrotrophic foodborne pathogen that has been
      implicated in outbreaks of foodborne illness involving cold-stored foods,
      especially milk and pork. A major mechanism bacteria use to adapt to cold is
      expression of cold shock proteins. The objective of this research was to study
      the expression of major cold shock proteins of Y. enterocolitica in Luria-Bertani
      (LB) broth, milk, and pork following a temperature downshift from 30 to 4 degrees
      C. Y. enterocolitica was inoculated into 10 ml of LB broth, sterile skim milk, or
      pork, and the samples were stored at 4 degrees C (cold shock) or 30 degrees C
      (control) for 0, 4, 8, 12, and 24 h. At each sampling time, total protein and
      total RNA were extracted from Y. enterocolitica harvested from LB broth, milk,
      and pork and subjected to two-dimensional gel electrophoresis and dot blot
      analysis. Two major cold shock proteins (CspA1 and CspA2) of approximately 7 kDa
      and their genes were expressed by Y. enterocolitica following cold shock.
      However, the CspA1 and CspA2 proteins were not expressed by Y. enterocolitica at
      30 degrees C. Y. enterocolitica CspA1 and CspA2 were observed as early as 2 h of
      cold shock in cultures from LB broth and milk and at 8 h of cold shock in
      cultures from pork.

PMID- 16300090
TI  - Inability of probiotic bacterial strains Lactobacillus rhamnosus HN001 and
      Bifidobacterium lactis HN019 to induce human platelet aggregation in vitro.
AB  - Platelet aggregation contributes to the pathogenesis of infective endocarditis,
      and aggregation of platelets induced by lactobacilli is thought to be an
      important contributory factor in the development and progression of Lactobacillus
      endocarditis. The main purpose of this study was to examine the effect of
      immunity-enhancing probiotic strains Lactobacillus rhamnosus HN001 and
      Bifidobacterium lactis HN019 on the activation and aggregation of human blood
      platelets. Whole blood samples from healthy individuals were incubated in vitro
      with HN001 or HN019 and subsequently labeled with platelet-specific monoclonal
      antibodies, fluorescein isothiocyanate-conjugated anti-CD41a (expressed on normal
      platelets), and phycoerythrin-streptavidin-conjugated anti-CD62p (expressed on
      activated platelets) before analysis by flow cytometry. Platelet-rich plasma was
      used to assist the gating of the platelet cluster. ADP and epinephrine were used
      as the physiological platelet activation agonists. Platelet aggregation-inducing
      strain Streptococcus sanguis 133-79 was used as a positive control strain. The
      mean fluorescence intensity of phycoerythrin and the percentage of platelets
      expressing the CD62p marker were used to assess the degree of platelet
      activation. The percentage of CD62p-positive platelets and the light scatter
      profiles of the agonist-activated platelets were used to identify the occurrence
      and degree of platelet aggregation. HN001 and HN019 had no effect on spontaneous
      platelet activation and aggregation; they also failed to exacerbate the platelet
      aggregation activity induced by ADP and epinephrine. Therefore, these test
      probiotic strains HN001 and HN019 are less likely to participate in the
      pathogenesis of infective endocarditis or other thrombotic disorders with regard
      to platelet aggregation factors.

PMID- 16300091
TI  - Influence of a test preservative on sponge cakes under different storage
      conditions.
AB  - A study was performed on 240 samples, divided into four batches, of sponge cakes
      baked following their industrial recipe to which different concentrations of a
      test preservative, mainly lactic acid and propylene glycol, were added. Each
      batch was submitted to three different temperature and relative humidity
      conditions. The counts of mesophilic aerobic bacteria, enterobacteria,
      enterococci, staphylococci, clostridia, lactic acid bacteria, and yeasts were
      less than 1 log CFU/g in all the batches studied and throughout the 120 days of
      study. Depending on batches and conditions, the mold counts were between less
      than 1 and 6.40 log CFU/g. Aspergillus, Eurotium, Penicillium, and Wallemia were
      detected and were potentially toxigenic in two cases. The test preservative added
      at 18 g/kg produced the greatest preserving effect, prolonging the product's
      shelf life by more than 4 months and showing itself to be effective at the other
      concentrations, especially at 15 degrees C and at 80 and 51% relative humidity.

PMID- 16300092
TI  - Aflatoxin B1 binding by a mixture of Lactobacillus and Propionibacterium: in
      vitro versus ex vivo.
AB  - Aflatoxin B1 (AFB) is a well-known carcinogen and reducing its bioavailability is
      of great interest for human and animal health. Several probiotic bacteria are
      able to bind AFB1 in vitro, including Lactobacillus rhamnosus LC-705 and
      Propionibacterium freudenreichii subsp. shermanii JS. A mixture of these two
      probiotics is used by the food and feed industry as biopreservative (Bioprofit),
      making it a promising candidate for future applications. Consequently, this study
      aims to investigate the in vitro and ex vivo ability of this probiotic mixture to
      bind AFB1. For in vitro experiments, probiotic mixture was suspended in an AFB1
      solution (5 microM), incubated for 1 to 30 min, centrifuged, and AFB1 residues
      were quantitated in supernatant and pellet. For ex vivo experiments, duodenal
      loops of chicks were ligated and injected with either AFB1 solution alone or
      probiotic mixture suspension and AFB1 solution. Lumen content was centrifuged and
      AFB1 was quantitated in supernatant and pellet. Additionally, AFB1 was extracted
      from duodenal tissue to calculate tissue uptake. In vitro, 57 to 66% of AFB1 was
      removed from the solution by the probiotic mixture, but only 38 to 47% could be
      extracted from the bacterial surface. In ex vivo experiments, only up to 25% of
      AFB1 was bound by bacteria, and tissue uptake of AFB1 was significantly reduced
      when probiotic bacteria were present in the duodenal loop. Furthermore, the
      effect of intestinal mucus on the bacterial binding ability was investigated in
      vitro and was found to significantly reduce AFB1 binding by the probiotic
      mixture. However, probiotic mixture could only retard but not prevent AFB1
      absorption in duodenal loops. Further work needs to assess the potential of
      probiotics in different experimental setups.

PMID- 16300093
TI  - Inhibitory activity of phosphates on molds isolated from foods and food
      processing plants.
AB  - Six commercial phosphates were evaluated for inhibition of the growth of 17 molds
      isolated from food sources. The assays were performed at neutral and natural
      (without pH adjustment) pH values, and the molds were streaked on plate count
      agar with added phosphates. Phosphate concentrations of 0.1, 0.3, 0.5, 1.0, and
      1.5% (wt/vol) were used, and the MIC was determined. The resistance of molds to
      phosphates depended on the species. At a neutral pH, Aspergillus ochraceus and
      Fusarium proliferatum were resistant to all phosphates at all concentrations
      assayed, and Byssochlamys nivea, Aureobasidium pullulans, and Penicillium glabrum
      were most sensitive. The most inhibitory phosphates were those with chain lengths
      greater than 15 phosphate units and the highest sequestering power. At natural pH
      values (resulting from dissolving the phosphate in the medium), inhibitory
      activity changed dramatically for phosphates that produced alkaline or acidic pH
      in the medium. Phosphates with alkaline pH values (sodium tripolyphosphate of
      high solubility, sodium tripolyphosphate, and sodium neutral pyrophosphate) were
      much more inhibitory than phosphates at a neutral pH, but sodium acid
      pyrophosphate (acidic pH) had decreased inhibitory activity. The results indicate
      that some phosphates could be used in the food industry to inhibit molds linked
      to food spoilage.

PMID- 16300094
TI  - Rapid depletion of marbofloxacin residues in rabbit after therapeutic treatment.
AB  - Although rabbit meat production represents a very small percentage of the world
      meat market, this percentage has been growing continuously during the last 30
      years. Rabbit is considered a minor food species, and therefore no drugs are
      specifically registered for this animal. This situation encourages rabbit farmers
      to make off-label use of antibacterial drugs authorized for food-producing animal
      species other than rabbits. In the present study, the distribution and
      elimination of the fluoroquinolone antibacterial agent marbofloxacin in rabbit
      muscle, liver, and kidney was investigated. Marbofloxacin was chosen as a
      representative of a new generation of antibacterial drugs active against most
      gram-positive and gram-negative bacteria and mycoplasms; it is well tolerated and
      has short elimination times in bovine and swine species. Rabbits were treated
      with marbofloxacin at 2 mg kg of body weight(-1) for 5 days. Residual
      concentrations in liver, kidney, and muscle tissues were determined posttreatment
      with high-performance liquid chromatography and fluorescence detection.
      Marbofloxacin was rapidly distributed and eliminated from rabbit tissues.
      Concentrations were higher in the liver and kidney than in muscle. However, 48 h
      after the end of treatment, marbofloxacin concentrations dropped below the
      maximum residue level fixed for this antibacterial drug in cattle and pigs.
      Considering the efficacy of marbofloxacin for the treatment of the most common
      rabbit diseases, its tolerability, and its short elimination time as verified in
      the present study, use of this antibacterial drug could be extended to
      therapeutic treatment of rabbits.

PMID- 16300095
TI  - [Preliminary remarks from the editor].

PMID- 16300096
TI  - [The German Research Council (DFG) and bio-medical research 1920-1970.
      Introduction].

PMID- 16300097
TI  - ["A model of joint research"? Cancer research and the funding policies of the
      German Research Foundation and the Reich Research Council in National Socialist
      Germany].
AB  - In 1936 the German Research Foundation (Deutsche Forschungsgemeinschaft) started
      planning a programme for tumour research. After discussions between
      representatives of the German Research Foundation, the Reich Health Office and
      the Ministry of Science and Education about the extent of the scheme, in December
      1936 the first scientists received their grants. The scheme was mainly drawn up
      by the Munich pathologist Max Borst, who was supported by the German Research
      Foundation's employee Sergius Breuer. Scientific research on cancer was divided
      into four sections: (1) etiology, (2) diagnosis, (3) treatment, and (4)
      constitution, disposition, heredity, and statistics. Well-known German scientists
      were invited to contribute to the scheme. When the Reich Research Council
      (Reichsforschungsrat) took over power in decision-making on research funding in
      1937, cancer research was not seriously affected. Only in 1943, when further
      restructuring of the Reich Research Council took place, the situation changed
      through Kurt Blome's becoming the plenipotentiary for cancer research. Blome's
      position in cancer research was linked with the task of supporting scientific
      research on biological and chemical warfare. In general, however, the
      characteristics of the cancer research scheme remained astonishingly constant up
      to the end of World War II.

PMID- 16300098
TI  - [Geneticists in the service of war? The German Research Foundation, the Reich
      Research Council, and policy changes in research on heredity].
AB  - Historical research has hitherto focused on the specific contribution of human
      genetics research to National Socialist racial hygiene. During the Third Reich
      this field had a key position and received very substantial financial support
      from the government. However, this state sponsorship during the Nazi period was
      not constant, as documents from the most important public funding organizations
      for academic research in Germany, the German Research Foundation (Deutsche
      Forschungsgemeinschaft) and the Reich Research Council (Reichsforschungsrat)
      show. Human genetics saw a reduction in sponsorship as the government shifted its
      spending towards preparations for the war. Accordingly, many human geneticists
      and racial hygienists were unable to continue their research or were forced to
      change the focus of their work. It is also important to note that much of the
      available funds were concentrated on the Kaiser Wilhelm Institute for
      Anthropology, Human Heredity and Eugenics. This essay analyzes the institutional
      context of science policy as well as the dynamics between the science of human
      heredity and Nazi politics during the war.

PMID- 16300099
TI  - [Continuity in personnel--change in contents: German physiologists in National
      Socialism and in the Federal Republic of Germany].
AB  - This paper illustrates how German physiologists during the Second World War
      succeeded in making a case for the relevance of their research for the war
      effort. In this way the paper contributes to the recent historical debate about
      how scientists--in this case the physiologists--could enforce their interests
      within the National Socialist system and to what extent they were "misused" by
      the political and military leaders. Most scientists were able to continue their
      careers in the new political system after 1945, using the old scientific network
      from the National Socialist era. They successfully changed their research topics,
      responding quickly to the new challenges in peace. As a typical example the
      career of the physiologist Hans Schafer is described in this article.

PMID- 16300101
TI  - Paediatric prescribing and the advent of the British National Formulary for
      Children (BNFc).

PMID- 16300100
TI  - [Reorientation of German tropical medicine--research on smallpox vaccine in post
      war Germany].
AB  - The German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) supported a
      reorientation of research in tropical medicine after the Second World War, in the
      direction of virus research, by financing relevant research projects and the
      establishment of entire departments, or by guaranteeing the subsistence of
      institutes. During the post-war period research was focussed on the smallpox
      vaccine, especially because severe vaccine-induced side effects, such as post
      vaccination encephalitis, attracted attention. Research on smallpox vaccination
      thus formed the backbone of German tropical medical research and its
      institutional basis, with the DFG providing the financial basis.

PMID- 16300102
TI  - Prevention of healthcare worker and nosocomal influenza.

PMID- 16300103
TI  - Contact tracing of tuberculosis in a school setting and the relevance of BCG in
      this population.
AB  - Tuberculosis (TB) remains a worldwide health problem. Treatment, contact tracing
      and screening of at-risk populations continue to be important issues even in
      countries with low rates of tuberculosis. In contact tracing, prior BCG
      vaccination can make interpretation of Mantoux positivity difficult. We had the
      opportunity to evaluate contacts of a student diagnosed with pulmonary
      tuberculosis. In the index case's class, 23 of 50 (46%) students screened had TB
      infection and a further 2 (4%) students had TB disease. Screening was offered to
      all students in the school (307 students) and 244 students (79%) attended.
      Students were stratified naturally into classes of ascending age, providing an
      opportunity to study disease transmission and Mantoux testing in a group who had
      received BCG at birth. Our findings illustrates that neonatal BCG vaccination has
      a minimal effect on Mantoux positivity at 12 years and older.

PMID- 16300104
TI  - Preservation of fertility in women affected by cancer. An audit of the
      cryopreservation services provided for women at Human Assisted Reproduction
      Ireland.
AB  - There has been a remarkable improvement in survival rates for adult and childhood
      cancers, due to progress in cancer treatments. However multiagent chemotherapy
      and radiotherapy are associated with gonadal failure. Whereas sperm banking is
      commonly performed, female gametes are not so amenable to cryopreservation.
      Options available to women for fertility preservation include, embryo and oocyte
      cryopreservation. Our unit established an oocyte/embryo cryopreservation service
      for women affected by cancer in October 2003. Ninteen women have been referred
      and five (26%) women have had oocytes cryopreserved. The mean age of women in the
      group cryopreserved was 34 years (range 21-41). Their mean day 3 FSH was 6.2 IU
      (range 5.5-6.8). The mean dose of rFSH used was 1870 units (range 1500-2600). The
      mean number of oocytes cryopreserved was 8 (range 3-16). Preservation of
      fertility is of major concern to women affected by cancer. This service offers
      them hope for their future fertility.

PMID- 16300105
TI  - A comparative study on attitudes, towards the provision of out-of-hours care, of
      the spouses of general practitioners participating, or not, in a rural out-of
      hours co-op.
AB  - Qualitative research has suggested that the stress of general practice, and that
      of out-of-hours care in particular, has an impact on general practitioners'
      (GPs') spouses. The effects on the families of practitioners, of the introduction
      of out-of-hours co-operatives has not been extensively studied. Our objective was
      to compare, between the spouses of GPs participating or not in a rural co-op, the
      effects of out-of-hours commitments on personal and family life. The spouses of
      all 125 GPs in a rural region in Ireland were sent questionnaires; 59 GPs were
      members of an out-of-hours co-op, 66 were engaged in traditional on-call rotas.
      Most questions were in statement form, to which participants were required to
      respond on a five point Likert rating scale. The response rate was 67%. Non-co-op
      spouses were significantly older than co-op spouses (48.3 years versus 42.6,
      t(68)=-3.02, p=0.04). 80% of the co-op group favoured a co-op for on-call cover
      as compared to 46% of the non-co-op group. The majority of respondents from both
      groups agreed that they dislike when their spouse is on call and that time spent
      on-call placed a strain on family life and was detrimental to their spouse's
      health. Spouses of non-co-op general practitioners were more likely to agree that
      their home life was interrupted by patients telephoning the house (z=-3.06,
      p=0.002) and by patients calling to the door without a prior appointment (z=2.9,
      p=0.004). They were also more likely to worry about the safety of their spouse on
      call (z=-2.07, p=0.038). The general provision of out-of-hours care has a
      significant impact on the spouses and families of GPs participating, or not, in a
      rural co-op. Spouses of participants in co-ops had significantly less
      interruptions to their home life from patients and worried less about the safety
      of their spouse. The implications of these findings on the recruitment and
      retention of rural practitioners merits further discussion.

PMID- 16300106
TI  - Oral bisphosphonates improve Bone Mineral Density in adults with cystic fibrosis.
AB  - In adults with Cystic Fibrosis (CF) we sought to establish the effect of oral
      bisphosphonate therapy. Bone densitometry measured by dual energy X-ray
      absorptiometry (DXA), and clinical patient data, were reviewed retrospectively.
      Eighty-one patients (median age 27 years) had baseline and follow-up DXA, with an
      interval of 19.2 +/- 7.1 months. Thirty-six patients were treated with
      bisphosphonates (alendronate=23 and risedronate=13). Median follow-up Bone
      Mineral Density in the bisphosphonate group was 3.7% greater at the lumbar spine
      (95%CI 1.9 to 5.7%, P<0.0005) and 2.4% greater at the femur (95%CI 0.8 to 3.9%,
      P<0.005) than the group not treated with bisphosphonates. Oral bisphosphonate
      therapy had a beneficial effect on BMD in adults with CF.

PMID- 16300107
TI  - Bullying of junior doctors prevails in Irish health system: a bitter reality.
AB  - Workplace bullying in health systems is a well known fact. It leads to not only
      breakdown in teamwork but also has significant affect on the individual's
      personal life. True prevalence of bullying in junior doctors working in Ireland
      is unknown. Our aim of study was to find out the prevalence of bullying in junior
      doctors working hospitals in south and western counties of Ireland and to assess
      its effects on the productivity of work and family life and to identify the
      common source of bullying. We carried out a questionnaire survey. A total of 950
      questionnaires were sent. Response rate was 51%. Our sample is 15% of the target
      population of all the hospital junior doctors. 30% of the responders claimed to
      be subjected to one or more bullying behaviors. Doctors from European Union (EU)
      reported significantly less rate of bullying compares to non EU doctors. Our
      results are in line with the results of studies conducted in United Kingdom. This
      study shows the magnitude and source of the problem. We conclude that bullying is
      a common problem in Irish health system. Increased awareness and zero tolerance
      are required to eradicate bullying.

PMID- 16300108
TI  - Screening for haemoglobinopathy--a comparison of two methods in an Irish
      maternity unit.
AB  - Two-pronged retrospective and prospective studies were carried out to compare
      opportunistic versus systematic screening for carriers of haemoglobinopathy in an
      Irish maternity unit. Identification was either performed opportunistically on
      the basis of ethnicity or systematically on the basis of a low mean corpuscular
      haemoglobin. A comparison was made between the numbers that were tested for
      haemoglobinopathy and subsequent detection rates. In the prospective study women
      were identified again on the basis of either ethnicity or a low MCH and all women
      identified were tested for haemoglobin variants. A comparison was made between
      the numbers tested and subsequent detection rates. In both studies systematic
      screening identified similar rates as opportunistic screening. However,
      opportunistic screening identified a greater absolute number of carriers. Our
      retrospective study showed a disappointing uptake of testing of those identified,
      regardless of the method of screening. Better identification of carriers requires
      that all those identified as at-risk of haemoglobinopathy carriage should be
      tested, irrespective of the method of screening.

PMID- 16300109
TI  - Human brucellosis in the Mid-West 2002-3.
AB  - Human brucellosis remains a serious public health issue in Ireland. Clinical
      notifications in the Mid-Western Area (HSE-MWA) underestimate the burden of
      illness and attendant morbidity in the region. The diagnosis of acute and chronic
      human brucellosis depends on the clinical evidence and the results from
      laboratory serological testing or culture on rare occasion. This study examined
      the clinical evidence behind locally defined serological "positives" in the HSE
      MWA from 2002 to 2003. Ninety cases were detected in 2002 and 31 in 2003. While
      sampling bias is likely to be present, aspects of brucellosis in Ireland were
      confirmed. Middle-aged males were most commonly affected. The majority of cases
      were linked to farming or veterinary practice. Symptoms such as sweats, fever and
      weight loss were commonly associated with acute brucellosis infection while
      malaise was common in acute and chronic brucellosis. A clear definition of what
      is notifiable is needed. Surveillance systems must appreciate the importance of
      both clinical and laboratory evidence to classify confirmed or probable
      brucellosis as paired sera were not common. Public health authorities must follow
      up the clinical aspects for accurate national statistics. General practitioners
      in the Mid-West appear to be vigilant regarding brucellosis in their patients.
      Regional zoonoses committees are useful in monitoring disease prevalence in human
      and animal populations without compromising confidentiality.

PMID- 16300110
TI  - Presentation of malignant melanoma metastases as a testicular lump.

PMID- 16300111
TI  - Juvenile myoclonic epilepsy masquerading as ecstasy withdrawal.

PMID- 16300112
TI  - Clopidogrel induced oral ulceration.

PMID- 16300113
TI  - Ischaemic stroke in dogs and humans: a comparative review.
AB  - Cerebrovascular accidents, also known as strokes, are one of the major causes of
      disability and mortality among adult humans. The increased availability of
      magnetic resonance imaging in veterinary medicine means they are being
      increasingly recognised in dogs, too. Cerebrovascular accident is defined as the
      sudden onset of non-progressive, focal brain dysfunction as a result of ischaemic
      infarction or haemorrhage. Focal ischaemic stroke is caused by interruption of
      the arterial blood flow to a dependent area of brain parenchyma by a thrombus or
      an embolus. Once the diagnosis of ischaemic stroke is confirmed, potential
      sources of thrombosis or embolism should be investigated and treated accordingly.
      Dogs with ischaemic stroke tend to recover within several weeks with supportive
      care only.

PMID- 16300114
TI  - Hyperparathyroidism in dogs with hyperadrenocorticism.
AB  - OBJECTIVES: To assess the effect of canine hyperadrenocorticism (HAC) on
      parathyroid hormone (PTH), phosphate and calcium concentrations. METHODS: PTH
      concentrations and routine biochemical parameters were measured in 68 dogs with
      HAC. Ionised calcium was measured in 28 of these dogs. The results obtained were
      compared with an age- and weight-matched group of 20 hospital patients that did
      not show signs of HAC. RESULTS: There were significant differences between the
      PTH, phosphate, alkaline phosphatase, creatinine and albumin concentrations
      between the two groups. Total and ionised calcium concentrations were not
      significantly different. Most of the dogs (92 per cent) with HAC had PTH
      concentrations that were greater than the reference range (10 to 60 pg/ml), and
      in 23 dogs they were greater than 180 pg/ml. There were significant positive
      correlations between the PTH and basal cortisol, post-adrenocorticotropic hormone
      (ACTH) cortisol and alkaline phosphatase concentrations, and also the phosphate
      and post-ACTH cortisol concentrations. CLINICAL SIGNIFICANCE: Adrenal secondary
      hyperparathyroidism is a cause of increased PTH concentrations and may be
      associated with abnormalities in calcium and phosphate metabolism in dogs with
      HAC. The findings of this study could explain why canine HAC may cause clinical
      signs such as calcinosis cutis that are associated with altered calcium
      metabolism.

PMID- 16300115
TI  - Canine hyperadrenocorticism: effects of trilostane on parathyroid hormone,
      calcium and phosphate concentrations.
AB  - OBJECTIVES: To determine the effects of treating canine hyperadrenocorticism
      (HAC) on parathyroid hormone (PTH), calcium and phosphate concentrations in dogs.
      METHODS: Serum calcium, phosphate and PTH concentrations were analysed in 22 dogs
      with HAC before treatment with trilostane and at a median of 210 days after
      commencing treatment. Pretreatment data were compared with data from an age- and
      weight-matched group of hospitalised patients, and post-treatment data were
      compared with pretreatment data. RESULTS: PTH and phosphate concentrations were
      significantly higher in dogs with HAC compared with control dogs. PTH
      concentrations reduced significantly with treatment, such that there was no
      longer a difference between the HAC and control groups. Phosphate concentrations
      also reduced significantly with treatment but there was still a significant
      difference between those in dogs with HAC and control dogs. Despite no
      significant difference between calcium concentrations in the pretreatment HAC and
      control groups, calcium concentrations increased significantly with treatment.
      CLINICAL SIGNIFICANCE: These results show that adrenal secondary
      hyperparathyroidism resolves with treatment and suggest that increased calcium
      and phosphate levels have a role in its pathogenesis.

PMID- 16300116
TI  - Immune-mediated haemolytic anaemia and thrombocytopenia associated with Anaplasma
      phagocytophilum in a dog.
AB  - A 10-year-old, crossbreed dog was presented with a history of severe lethargy,
      pyrexia and inappetence of several days' duration. Clinical examination revealed
      pallor of the mucous membranes, petechiae, generalised lymphadenopathy and
      effusions in multiple joints. Laboratory evaluation showed severe anaemia and
      thrombocytopenia, with positive in-saline agglutination and the presence of
      antiplatelet antibodies. The DNA of Anaplasma phagocytophilum, an endemic
      granulocytic rickettsial parasite, was detected by PCR. A poor response to
      doxycycline and immunosuppressive therapy with corticosteroids was seen.
      Euthanasia was performed after the development of disseminated intravascular
      coagulation. Postmortem examination demonstrated changes consistent with the
      development of disseminated intravascular coagulation and infection with
      granulocytic ehrlichiosis. This case documents the presence of canine
      granulocytic ehrlichiosis caused by A phagocytophilum in the U.K., and highlights
      the range of clinical signs and clinicopathological abnormalities that may be
      observed in infected dogs.

PMID- 16300117
TI  - Myocarditis and generalised vasculitis associated with leishmaniosis in a dog.
AB  - A three-year-old, female bulldog was presented with bilateral uveitis, apathy,
      listlessness, generalised lymphadenopathy and perivulvar haematoma. The initial
      laboratory studies showed non-regenerative anaemia, polyclonal gammopathy and a
      high urine protein:creatinine ratio. Serology for leishmaniosis was positive and
      treatment with allopurinol and meglumine antimoniate was started. Despite
      treatment, the dog's clinical condition deteriorated. Signs included cutaneous
      ecchymosis, respiratory distress and finally cardiorespiratory arrest.
      Histopathological studies of postmortem tissue samples revealed a generalised
      vasculitis of several internal organs and severe myocarditis. Leishmania species
      organisms were identified in affected tissues using immunoperoxidase labelling
      and PCR techniques.

PMID- 16300118
TI  - L-thyroxine responsive cricopharyngeal achalasia associated with hypothyroidism
      in a dog.
AB  - An eight-year-old, male boxer dog was presented with a one-month history of
      hindlimb weakness followed by compulsive ineffective drinking, dysphagia,
      regurgitation and nasal reflux during drinking. A neurological examination
      revealed weakness and conscious proprioception deficits in both hindlimbs with
      normal spinal reflexes. The dog's swallowing function was examined by
      fluoroscopy. This showed normal prehension of the barium paste, bolus formation
      and contraction of the pharyngeal muscle, but no opening of the upper oesophageal
      sphincter was detected. A serum thyroid stimulating hormone level of 0.402 ng/dl
      and serum total T4 of 0-01 microg/dl were determined. The dog fully recovered one
      month after L-thyroxine therapy. The association found between cricopharyngeal
      achalasia and hypothyroidism suggests that hypothyroidism should be included in
      the list of differential diagnoses for dogs with cricopharyngeal achalasia.

PMID- 16300119
TI  - What is your diagnosis? Intracranial meningiomas.

PMID- 16300120
TI  - Standardisation projects: some history and an update.

PMID- 16300121
TI  - [A method for visualising the therapeutic effect in orthodontics: superposition
      over the Np-Es-Tm angle bisection].
AB  - Many methods of superimposition exist and vary according to selected reference
      landmarks. Basal and alveolar structures are not easily dissociable, the results
      of the growth and the therapeutic effects strongly overlapping. The method of
      superimposition the authors propose eliminates the overall effects of growth,
      showing only the therapeutic effects.

PMID- 16300122
TI  - [The need for orthodontic treatment. Justification and methods of evaluation
      (part 1)].
AB  - Most adolescents in developing countries undergo orthodontic treatment. Three
      main reasons are routinely cited to justify the provision of orthodontic
      treatment i.e. the improvement of facial and/or dental aesthetic, the
      preservation of the health and functioning of the dentition. Orthodontic indices
      have been devised to minimise the subjectivity related to the classic orthodontic
      diagnosis. These indices can be classified under five headings: nosological,
      epidemiological, treatment need, outcome and complexity.

PMID- 16300123
TI  - [Individualized clinical evaluation of tooth movement. Treatment of Class II:
      molar splints and structural effects].
AB  - The presentation of a synoptic chart allowing a dental arch analysis and Class II
      correction strategy is presented and followed by a study on 30 patients in mixed
      dentition and 37 growing patients in permanent dentition. These patients
      presenting a Class II malocclusion have been treated by Class II mechanics and
      lower molar individualised splint enhancing the vertical lower face height and
      skeletal Class II correction. This study shows a good vertical stabilization of
      the facial planes during the treatment, a significant growth of the lower face
      but it is noticed a posterior rotation of the occlusal plane in the mixed
      dentition sample.

PMID- 16300124
TI  - [Clinical study of orientation and reference planes in cephalometry].
AB  - A critical study of orientation and reference planes used in cephalometrics is
      undergone. The data consists of cephalometric measurements evaluated in a sample
      of 90 young lebanese adults, divided into 43 girls and 47 boys, whose lateral
      cephalograms were registered according to the natural head position. This study
      shows the importance of the true horizontal as orientation and reference planes,
      due to the high reproducibility of the natural head position, and the high
      variability of the intra-cranial reference planes as compared to the true
      vertical, as well as the low correlation among measurements based on the true
      horizontal as a reference plane (AB-horizontal), and the measurements based on
      the intra-cranial planes and points (ANB) as reference. This study also evaluated
      the variations of some angular and sagittal measurements (SNA, SNB, SNPog)
      registered according to two orientations: Frankfort plane and the natural head
      position.

PMID- 16300125
TI  - [Musculoskeletal connections. Study of two cases of oto-mandibular dysplasia].
AB  - The current genetic data stress the importance of musculo-skeletal connections in
      the development of a coherent system connecting the tendons and aponeurosis
      muscles with the osseous parts. The observations in tomodensitometry of musculo
      skeletal connections in otomandibular dysostosis make it possible qualitatively
      to observe the development of the muscles and their functions.

PMID- 16300126
TI  - [Orthopedic aspects of Distal Active Concept therapy applied in the mixed
      dentition. Comparative study with an untreated population].
AB  - Our present study compares the skeletal and dentoalveolar changes between 120
      subjects in mixed dentition treated with "Distal Active Concept" therapy versus
      157 untreated subjects of class II served as a control group. Upon considering
      the treated subjects, a highly significant difference of mandibular growth (p <
      or = 0.001) with an anticlockwise rotation is noticed. The comparisons done
      according to gender and facial divergence show that the linear measurements are
      greater in males than females but the vertical relations are identical. Moreover,
      when considering hypodivergent and normodivergent subjects, all cephalometric
      values are similar and when regarding treated or non treated subjects, a
      significant difference of vertical growth factors exists and prevails. After
      comparaison, results clarify the benefits of early treatment for Class II
      malocclusion when the skeletal imbalance is considerable as it causes a quick
      mandibular response and hence improving the facial harmony dramatically.

PMID- 16300127
TI  - [Facial surgery for rejuvenation].
AB  - Aging brings about anatomical changes that are undesirable. Senescence is
      consequently one of the most powerful stimuli for aesthetic surgery. The face,
      responsible for the myriad expressions of human experience, is constantly subject
      to exposure and also suffers from the perennial action of environmental factors
      and gravity. Frequently, the face is the main focus of anxiety in individuals who
      have attained a certain age, presenting skin flaccidity and loss of tone, marked
      lines of expression and fat deposits. Expectations of both the patient and the
      surgeon, regarding facial aesthetic surgery, have increased considerably over the
      last two decades with the advent of newer procedures and equipment. While
      experience allows the surgeon a better selection of techniques, at the same time
      he must be knowledgeable in details of different surgical approaches and
      variations to attain the best result for each individual case. The anatomy of the
      aging face should be examined carefully for a personalized treatment plan.
      Currently, a satisfactory result of an aesthetic facial procedure is obtained
      when signs of an operation are undetectable and no anatomical landmarks have been
      altered. The bond created between the patient and surgeon will be frustrated if
      there remain signs that reveal the "secret" that surgery was performed.

PMID- 16300128
TI  - Serogrouping of pathogenic Escherichia coli isolated from carcasses of new born
      Friesian calves at Benghazi and their sensitivity to certain antibiotics.

PMID- 16300129
TI  - Symmetrical poliomalacia of sheep in Ibadan, Nigeria.

PMID- 16300130
TI  - Trypanosomiasis in N'Dama and White Fulani heifers exposed to natural infection
      on a ranch in Western Nigeria.

PMID- 16300131
TI  - Heterophile antibodies in experimental trypanosomiasis: level of antibodies in
      Trypanosoma gambiense infection.

PMID- 16300132
TI  - Animal trypanosomiasis in Zambia: incidence in cattle in Southern Province.

PMID- 16300133
TI  - Muellerius capillaris in goats and sheep in Uganda.

PMID- 16300134
TI  - The role played by wild carnivores in the epidemiology of bovine cysticercosis in
      Kenya.

PMID- 16300136
TI  - Prevalence of Cysticercus bovis in the North-Eastern State of Nigeria.

PMID- 16300135
TI  - The incidence and location of Cysticercus bovis in Nigerian cattle.

PMID- 16300137
TI  - Host reactions in rabbits experimentally infected with Fasciola gigantica.

PMID- 16300138
TI  - Prevalence and experimental transmission of bovine piroplasms in northern
      Nigeria.

PMID- 16300140
TI  - Clinical and experimental observations on the therapeutic value of chloroquine
      against balantidiosis in pigs.

PMID- 16300139
TI  - Prevalence and significance of blood parasites in dogs in Zaria, northern
      Nigeria.

PMID- 16300141
TI  - Salient non-disease problems of livestock production in Africa.

PMID- 16300142
TI  - Therapy trial using betamethasone in addition to specific treatment with a
      diamidine and quinuronium derivate in cattle experimentally infected with Babesia
      bigemina.

PMID- 16300143
TI  - Manganese (Mn) nutrition of the pig: the flux patterns of Mn from different
      sources in the gastrointestinal tract of the growing pig.

PMID- 16300144
TI  - Selenium--vitamin E deficiency in chicks.

PMID- 16300145
TI  - Cyanotoxicity of Adenium volkensii (Harms) compared with that of cassava.

PMID- 16300146
TI  - Fibrin stabilizing factor (factor XIII) activity in liver cirrhosis.

PMID- 16300147
TI  - [Further information about the African horse sickness virus].

PMID- 16300148
TI  - The effect of "xanthinol niacinate" on platelet aggregation.

PMID- 16300149
TI  - Carriers of hemophilia A.

PMID- 16300150
TI  - The effect of direct current cardioversion on coagulation.

PMID- 16300151
TI  - Hematoma of the rectus abdominis muscle simulating the distorsion of the ovarian
      cyst in the course of anticoagulant therapy.

PMID- 16300152
TI  - Benign investigation of essential hypertension.

PMID- 16300153
TI  - Experimental orthotopic liver transplantation.

PMID- 16300154
TI  - The effects of morphine on the heart rate in normal or morphine-tolerant rats.

PMID- 16300155
TI  - Comparative studies on blood clotting activity of the arterial and venous blood
      in normal and patients with atherosclerosis.

PMID- 16300156
TI  - Detection of bronchopleural fistula by gas analysis method of the pleura.

PMID- 16300157
TI  - Preparation of a standard brain thromboplastin.

PMID- 16300158
TI  - Biological role of indolealkylamine derivatives.

PMID- 16300159
TI  - The French healthcare system: presentation, changes and challenges.

PMID- 16300160
TI  - Building capacity for public health research.

PMID- 16300161
TI  - Management of hospitals in Aceh during the tsunami.
AB  - On December 26th, 2004, Aceh and its vicinity was hit by two natural forces
      consecutively, an earthquake and a tsunami. Hundreds of thousands of people
      perished, leaving the remaining of about the same number to become refugees. The
      writer was assigned by the Ministry of Health to Aceh on duty on the second and
      third week after the catastrophe, to help the management of Zainoel Abidin
      General Hospital in Banda Aceh, the province's biggest hospital, revive its
      operation.

PMID- 16300162
TI  - Experiences of a hospital in Thailand in treating tsunami patients.
AB  - No one was prepared when the tsunami hit on that sunny Sunday morning of 26
      December 2004--not the villagers, not the hotel employees, not the tourists on
      holiday enjoying the clear skies and calm waters. Yet days later, Bumrungrad
      International Hospital (BI), a Joint Commission International-accredited, 554-bed
      medical centre in Bangkok, Thailand, quickly became prepared as it began treating
      patients from the tsunami. This article highlights the efforts of Bumrungrad
      International Hospital in treating tsunami patients. Information for this article
      has been provided by Bumrungrad International's Senior Management team.

PMID- 16300163
TI  - Diabetes care in China: meeting the challenge.
AB  - In both human and economic terms, diabetes is becoming one of the most serious
      and costly health conditions worldwide. Economic development, bringing changes
      from a traditional to a modernized lifestyle, is driving a huge increase in the
      number of people with obesity-related type 2 diabetes in China. The extraordinary
      size of the problem is worrying; if current trends continue, diabetes will become
      a massive health burden in China. In this article, Changyu Pan looks at the
      status of diabetes care in China and highlights the need for regional and
      national initiatives to increase awareness amongst the general population of the
      risk factors for diabetes, and thus prevent a further rapid increase in the
      prevalence of the condition.

PMID- 16300164
TI  - Open source approaches to health information systems in Kenya.
AB  - This paper focuses on the experience to date of an installation of a Free Open
      Source Software (FOSS) product, Care2X, at a church hospital in Kenya. The FOSS
      movement has been maturing rapidly. In developed countries, its benefits relative
      to proprietary software have been extensively discussed and ways of quantifying
      the total costs of the development have been developed. Nevertheless, empirical
      data on the impact of FOSS, particularly in the developing world, concerning its
      use and development is still quite limited, although the possibilities of FOSS
      are becoming increasingly attractive.

PMID- 16300165
TI  - The global chronic care epidemic and international expansion of disease
      management programmes.

PMID- 16300166
TI  - Influence of renal dysfunction on the pharmacokinetics of the selective Na+/H+
      exchange inhibitor EMD 87 580 in patients with chronic heart failure.
AB  - BACKGROUND: Chronic heart failure (CHF) is a potential indication for the
      administration of EMD 87 580, a selective Na+/H+ exchange inhibitor. CHF is often
      accompanied by renal dysfunction, which is known to affect the pharmacokinetics
      of compounds predominately cleared by the kidneys. We examined the influence of
      renal dysfunction on the pharmacokinetics of EMD 87 580 in patients with CHF.
      METHODS: 21 patients with CHF and normal renal function (Group 1) and 9 patients
      with CHF and renal dysfunction (Group 2) received EMD 87 580 orally over 8 days.
      The mean creatinine clearance (CrCl) in Group 1 was 99.7 ml/min. 12 patients in
      this group were randomized to receive two doses of EMD 87 580 (7 patients 2 x 50
      mg and 5 patients 2 x 100 mg). The 9 patients in Group 2 with renal dysfunction
      (mean CrCl = 49.5 ml/min) received 50 mg EMD 87 580 once daily. Plasma and urine
      samples were collected for pharmacokinetic assessment. RESULTS: In CHF patients
      with renal dysfunction EMD 87 580 clearance was reduced to approximately 50%
      compared to Group 1, i.e. 6.80 ml/min (4.89-11.60) vs. 12.73 ml/min (8.93-22.21),
      p < 0.05, for the 50 mg dose and 14.08 ml/min (9.96-18.10), p < 0.05, for the 100
      mg dose. Consequently, plasma concentrations were increased in patients with
      renal dysfunction; AUC0-infinity 7,354 ng/ml x h (4,311-10,232) vs. 3,928 ng/ml x
      h (2,251-5,596, 50 mg dose, p < 0.05). A significant correlation was observed
      between EMD 87 580 plasma clearance and CrCl (r2 = 0.8062). CONCLUSION: In CHF
      patients with renal dysfunction EMD 87 580, clearance is reduced and plasma
      concentrations increased. Therefore, dose adjustments for EMD 87 580 are
      indicated in patients with CHF and renal dysfunction.

PMID- 16300167
TI  - Midazolam and its metabolites in brain death diagnosis.
AB  - OBJECTIVE: There is only limited knowledge on the pharmacokinetics of midazolam
      and its active metabolites in potential organ donors. Before establishing the
      diagnosis of brain death, drugs interfering with the neurological assessment have
      to be washed out. National guidelines advise a waiting time of 12 hours. The aim
      of our study was to evaluate whether it is sufficient to rely on a calculated
      waiting time. METHODS: As examples of typical pharmacokinetics of midazolam and
      its metabolites, we followed the concentration over time in four potential organ
      donors with immunoassays and high-performance liquid chromatography (HPLC).
      RESULTS AND CONCLUSIONS: In each of the 4 patients studied, the elimination of
      midazolam and/or midazolam metabolites was delayed. As long as brain death
      diagnosis requires that drugs interfering with the clinical assessment must be at
      levels below the therapeutic range, monitoring of midazolam and metabolites
      appears mandatory.

PMID- 16300169
TI  - Variability in clinical data is often more useful than the mean: illustration of
      concept and simple methods of assessment.
AB  - BACKGROUND: Clinical investigators, although they are generally familiar with
      testing differences between averages, have difficulty testing differences between
      variabilities. OBJECTIVE: To give examples of situations where variability is
      more relevant than averages and to describe simple methods for testing such data.
      RESULTS: Examples include: (1) testing drugs with small therapeutic indices, (2)
      testing variability in drug response, (3) assessing pill diameters or pill
      weights, (4) comparing patient groups for variability in patient characteristics,
      (5) assessing the variability in duration of clinical treatment, (6) finding the
      best method for patient assessment. Various fields of research, particularly in
      clinical pharmacology, make use of test procedures that implicitly, address the
      variability in the data. Tests specially designed for testing variability in data
      include the chi2-test for one sample, the F-test for 2 samples and Bartlett's or
      Levene's test for 3 or more samples. Additional methods include (1) the
      comparison of confidence intervals, and (2) testing confidence intervals against
      prior defined intervals of therapeutic tolerance or equivalence. Many of these
      tests are available in Excel and other statistical software programs and one such
      program is described. CONCLUSIONS: In the analysis of clinical data the
      variability in the data is often more important than averages. Eight simple
      methods for assessment variability are described to illustrate the value and
      importance of putting more emphasis on and this parameter.

PMID- 16300168
TI  - Pharmacokinetic interactions of the oral renin inhibitor aliskiren with
      lovastatin, atenolol, celecoxib and cimetidine.
AB  - OBJECTIVE: Aliskiren is the first in a new class of orally effective renin
      inhibitors for the treatment of hypertension. This study investigated the
      interaction profile of aliskiren, which is of clinical importance because
      hypertensive patients often require concomitant drug therapy for associated
      comorbidities. METHODS: Four separate studies investigated the pharmacokinetic
      interaction between single oral doses of aliskiren and lovastatin, atenolol,
      celecoxib or cimetidine, respectively. All studies involved healthy male
      volunteers aged 18-45 years. In 3 studies, subjects (n = 15 in each study)
      received single doses of aliskiren 150 mg alone, the test drug alone (lovastatin
      40 mg, atenolol 100 mg or celecoxib 200 mg), or both drugs in combination,
      according to a 3-period crossover design. In the cimetidine study (n = 12),
      aliskiren 150 mg was administered alone or concomitantly with cimetidine 800 mg
      according to a two-period crossover design. Plasma concentrations of aliskiren
      and test drugs were determined by liquid chromatography and mass spectrometry
      methods. Pharmacokinetic parameters were derived from these data. RESULTS: Mean
      AUC and t1/2 for aliskiren were not significantly changed by lovastatin, atenolol
      or celecoxib (< 10% difference between treatments). Aliskiren mean Cmax was not
      affected by either lovastatin or atenolol, although a non-significant 36%
      increase was observed with celecoxib. Modest, non-significant increases in
      aliskiren systemic availability followed coadministration with cimetidine
      (aliskiren mean AUC, Cmax and t1/2 increased by 17%, 19% and 15%, respectively).
      Aliskiren coadministration had no significant effect on the disposition of
      lovastatin, atenolol or celecoxib. CONCLUSIONS: Overall, single doses of
      aliskiren showed no evidence of clinically important pharmacokinetic interactions
      with lovastatin, atenolol, celecoxib or cimetidine.

PMID- 16300170
TI  - Statin toxicity: a situation that mimics viral hepatitis.
AB  - A case is presented involving a female patient who experienced rhabdomyolysis
      following high-dose therapy with a statin. Acute renal failure was a complicating
      factor necessitating the use of hemodialysis. The patient recovered fully within
      about 6 weeks.

PMID- 16300171
TI  - Bioequivalence of diclofenac injection formulations assessed in Korean males.
AB  - A bioequivalence study of diclofenac injection (test formulation (diclofenac
      potassium): HANA, reference formulation (diclofenac sodium): Shinpoong) was
      conducted in 18 healthy male Korean volunteers who received each medicine at a
      dose of 75 mg in a 2 x 2 crossover study. There was a one-week washout period
      between the doses. Plasma concentrations of diclofenac were monitored by high
      performance liquid chromatography over a period of 24 hours after the i.m.
      injection. AUC0-24 (the area under the plasma concentration-time curve from time
      0-24 hours) was calculated by the linear-log trapezoidal method. Cmax (maximum
      plasma drug concentration) and tmax (time to reach Cmax) were compiled from the
      plasma concentration-time data. Analysis of variance was carried out using
      logarithmically transformed AUC0-24 and Cmax, and non-transformed tmax. There
      were no significant differences between the medications in AUC0-24 and Cmax. The
      point estimates and 90% confidence intervals for AUC0-24 (parametric) and Cmax
      (parametric) were 0.973 (0.8971 to 1.0557) and 0.993 (0.9452-1.0451),
      respectively, satisfying the bioequivalence criteria of the European Committee
      for Proprietary Medicinal Products and the US Food and Drug Administration
      Guidelines. The corresponding value for tmax was 0.75 (0.00 to 1.00). Moreover,
      the modified Pitman-Morgan's adjusted F-test indicated that the bioavailabilities
      of diclofenac in the two medications were comparable regarding intra- and
      interindividual variability. Therefore, these results indicate that the two
      medications of diclofenac are bioequivalent and, thus, may be prescribed
      interchangeably.

PMID- 16300172
TI  - Health-related quality of life: gender differences in childhood and adolescence.
AB  - OBJECTIVES: To assess whether gender and age differences can be found in
      different aspects of health-related quality of life (HRQOL) of children and
      adolescents, and to what extent these results correspond to theoretical and
      empirical findings from developmental psychology. METHODS: A newly developed
      HRQOL questionnaire was completed by 3,710 youths aged nine to 17 years in seven
      European countries. The "Kidscreen 52" questionnaire consists of 10 scales
      operationalising aspects of the physical, psychological and social dimensions of
      HRQOL. With the use of ANOVA and effect sizes, the influence of age and gender on
      aspects of HRQOL is reported. RESULTS: Children report a very good quality of
      life largely independent of gender. After 12 years, HRQOL decreases in the
      majority of aspects. In the physical and psychological dimensions, a stronger
      decrease is found for females than for males. CONCLUSIONS: Children have higher
      HRQOL than adolescents in many aspects. With increasing age, HRQOL is frequently
      worse for females than for males. Examination of the individual aspects leads to
      a differentiation of the results with relevance for public health.

PMID- 16300173
TI  - [The version 2.0 of the SF-36 Health Survey: results of a population
      representative study].
AB  - OBJECTIVES: The SF-36 is an internationally approved instrument to assess
      subjective health. In its second version the SF-36 contains modifications to
      version 1.0 in several item formulations and response categories. The second
      version is translated in German but a psychometric analysis and standardisation
      are still lacking. METHODS: The SF-36, version 2.0, was administered in a
      representative German sample (n = 2043), analysed concerning its scale structure,
      reliability, dissemination characteristics and differences in traits of
      populations and compared to version 1.0 (German health survey). RESULTS: Version
      2.0 shows high reliability in subscales and has a scale structure which is
      comparable to that of version 1.0. The scale values in the actual population
      representative sample survey are rather distributed obliquely and effects of sex,
      age and residence (Eastern/Western Germany) have been found in regression
      analyses. CONCLUSION: The psychometric comparability of both versions is given
      but should interpreted with caution as regards content because of the different
      enquiry periods. Though the expected gain in psychometric quality and
      discrimination of version 2.0 to version 1.0 is evident, but does not justify a
      preference to version 2.0.

PMID- 16300174
TI  - Differential inequity in health expectancy by region in Belgium.
AB  - OBJECTIVES: To evaluate the size of social inequities in health between regions
      in Belgium using a composite health measure, the disability free life expectancy
      (DFLE). METHODS: Mortality data (5-years follow-up of the 1991 census) are
      combined with the 1997 Health Interview Survey to estimate the DFLE by education.
      Differences in partial life expectancy25-74 (LE25-74) and in DFLE25-74 between
      those at the bottom and those at the top of a relative social scale are used to
      compare the regional inequities. RESULTS: The higher educated person has a longer
      LE, with more years free of disability and less years with disability (in years:
      Flemish males: LE = 46.48; DFLE = 42.08; Walloon males: LE = 44.92; DFLE = 39.80;
      Flemish females: LE = 47.90; DFLE = 41.93; Walloon females: LE = 46.90; DFLE =
      39.84) compared to the population at the bottom of the education hierarchy (in
      years: Flemish males: LE = 44.86; DFLE = 30.16; Walloon males: LE = 42.77; DFLE =
      27.00; Flemish females: LE = 46.86; DFLE = 28.30; Walloon females: LE = 45.44;
      DFLE = 25.30). The inequity in LE and in DFLE is larger in the Walloon Region
      than in the Flemish Region. Only the regional difference in inequity in LE is
      statistically significant. CONCLUSION: The DFLE can be used to monitor the size
      of health inequities.

PMID- 16300175
TI  - [The importance of social relationships for the association between social
      inequality and health among the aged].
AB  - OBJECTIVES: To analyse whether the association between social inequality and
      health among the aged is mediated through social relationships (differential
      exposure hypothesis). Moreover, it is examined whether the association between
      social relationships and health is stronger in lower socio-economic groups
      (differential vulnerability hypothesis). METHODS: The analyses are based on a
      telephone survey of 682 older people (> or = 60 years) living in a private
      household in Germany. Education, income and occupational status are utilised as
      indicators of the socio-economic status. Quantitative (social contacts) as well
      as qualitative indicators (emotional support) of social relationships are used.
      Respondents were asked how often they meet their friends and relatives. Emotional
      support was measured by an instrument assessing the availability of a confidant
      and the perceived adequacy of the emotional support received. Self-rated health,
      depression (CES-D) and functional limitations are introduced as health
      indicators. RESULTS: Multiple logistic regression analyses show that the
      mediating effect of social relationships on the association between socio
      economic status and health (self-rated health, depression and functional
      limitations) among the aged is weak. Results concerning the differential health
      impact of social relationships in different socio-economic groups are
      inconsistent. DISCUSSION: Results do not support the differential exposure
      hypothesis saying that social inequalities in health can be explained by social
      relationships. Results do not support the differential vulnerability hypothesis
      either as there is no evidence for a stronger association between social
      relationships and health in lower socio-economic groups.

PMID- 16300176
TI  - [Immunization of 28 months old children in Geneva, Switzerland: trend over a 6
      year period, 1995-2000].
AB  - OBJECTIVES: Trend in immunization coverage of 28 months old children in Geneva,
      1995-2000. METHODS: Comprehensive analysis of routinely collected child
      immunization cards. Sample survey of non-responding parents. RESULTS: Among
      25,288 children (response rate, 91%) immunization coverage (three doses) was 96%
      for diphtheria and tetanus, 94% for whooping-cough and poliomyelitis and 84% for
      Haemophilus influenzae. Immunization coverage was 88% for measles (one dose).
      There was no significant change over time. CONCLUSIONS: Immunization coverage can
      be monitored by routinely collecting data from child immunization cards. Measles
      vaccination coverage is too low to prevent epidemics in Geneva.

PMID- 16300177
TI  - Relationships between unfavourable health status and smoking cessation attempts
      in Hungary.
AB  - OBJECTIVES: The study examines associations between intentions to quit smoking
      and health status in three age groups of Hungarian smokers, along with social
      demographic background variables. METHODS: In 2002, a cross-sectional
      representative health survey of the sample of 12668 adults was conducted in
      Hungary. The associations between health status and intentions to quit smoking
      were analysed with logistic regression among current smokers (N = 3408). The
      influence of health-related and social predictor variables was tested separately
      in different age groups (18-34, 35-49, 50-64, >65). RESULTS: Experiences of chest
      pain principally motivate young adults to quit smoking. Middle-aged smokers
      consider quitting because of suffering from cardio-vascular disease. Among the
      oldest, only respiratory disease influenced quitting attempts. Among social
      background variables only the fact of living with a spouse had an influence,
      gender and socio-economic status did not. CONCLUSIONS: Connections between health
      status and quitting intentions are weakening as age is increasing. The population
      seems to become gradually conscious of the connections between circulatory
      problems and smoking. Quitting attempts are restrained by the general attitude
      that ill health is a normal part of the ageing process.

PMID- 16300178
TI  - Veterinary education in South Africa: the class of 1927.
AB  - Joan Morice, a member of the class of 1927, broke the tradition of male student
      domination at the Onderstepoort Veterinary Faculty, but it took almost 20 years
      before other young ladies started following her courageous example. The
      accompanying photograph is unusual in the sense that the students appear in their
      then customary white coats instead of graduation regalia and that their dean is
      absent. Concise descriptions are given of the life histories of the 8 graduates.
      Their careers show more variation than in previous years. Only 1 of them spent
      his entire career at the Onderstepoort Research Institute and its Faculty,
      whereas another left the Institute after several years for a well-known
      pharmaceutical company in the United Kingdom. Although 1 entered private practice
      shortly after qualifying, she did not make it her permanent career and sadly died
      at the early age of 44. Another made the move from the field into private
      practice fairly late in his productive life. One left South Africa to spend most
      of his career in the Colonial Service in Tanganyika (now Tanzania) and later even
      joined the FAO in Rome. Two spent their entire careers in the field as state
      veterinarians--1 died at the age of only 43--and a third moved from the field to
      a locally-based pharmaceutical company.

PMID- 16300179
TI  - Lymphangiosarcoma of dogs: a review.
AB  - Lymphangiosarcoma in dogs, an extremely rare tumour with only 16 cases reported
      in the literature, is reviewed. Lymphangiosarcoma in humans, also very rare, and
      known in post-mastectomy, chronically-lymphoedematous patients as 'Stewart
      Treves' syndrome, is briefly outlined, as well as the various other causes of
      lymphoedema, both primary and secondary, which usually precede malignancy.
      Comparisons between human and canine lymphoedema are made when such references
      were found. The genetic links to primary lymphoedema and the manifestation
      thereof in humans are mentioned. Lymphangiosarcoma in the majority of human and
      canine patients is an aggressively malignant tumour with few patients surviving
      despite various attempted treatments. The tumour most commonly arises in the
      subcutaneous tissues and rapidly invades underlying tissues and may spread widely
      internally via haematogenous and lymphatic routes, with frequent pleural and
      chest involvement. The tumour has been reported mostly in medium- to large-breed
      dogs, in slightly more males than females, and in an age-range of 8 weeks to 13
      years, with more cases aged 5 years and older. Methods of diagnosis, with the
      variations encountered, including routine histopathology, immunohistochemistry,
      electron microscopy, tissue culture characteristics and endothelial expression of
      glycocongugates, are discussed.

PMID- 16300180
TI  - Diagnosis of suspected hypovitaminosis A using magnetic resonance imaging in
      African lions (Panthera leo).
AB  - Vitamin A deficiency is described in captive lions. Ante mortem diagnosis can
      either be made by serum analysis or liver biopsy, both of which may be
      problematic. This study utilised magnetic resonance imaging to identify vitamin A
      deficiency in lions with relatively mild clinical signs, which could otherwise be
      attributed to numerous other neurological conditions. Magnetic resonance imaging
      is a non-invasive, reliable diagnostic tool to demonstrate pathology typically
      associated with this condition. To accommodate varying lion ages and sizes, a
      number of cranium and brain measurements were compared with that of the maximum
      diameter of the occular vitreous humor. Occular ratios of the tentorium cerebelli
      osseum and occipital bone were most reliable in diagnosing the thickened osseous
      structures characteristic of hypovitaminosis A. The ratio of maximum:minimum
      dorsoventral diameter of the C1 spinal cord was also of value.

PMID- 16300181
TI  - Comparison of effects of uncomplicated canine babesiosis and canine normovolaemic
      anaemia on abdominal splanchnic Doppler characteristics--a preliminary
      investigation.
AB  - A preliminary study was conducted to compare uncomplicated canine babesiosis (CB)
      and experimentally induced normovolaemic anaemia (EA) using Doppler
      ultrasonography of abdominal splanchnic vessels. Fourteen dogs with uncomplicated
      CB were investigated together with 11 healthy Beagles during severe EA, moderate
      EA and the physiological state as a control group. Canine babesiosis was compared
      with severe EA, moderate EA and the physiological state using Doppler variables
      of the abdominal aorta, cranial mesenteric artery (CMA), coeliac, left renal and
      interlobar, and hilar splenic arteries, and the main portal vein. Patterns of
      haemodynamic changes during CB and EA were broadly similar and were characterised
      by elevations in velocities and reductions in resistance indices in all vessels
      except the renal arteries when compared with the physiological state. Aortic and
      CMA peak systolic velocities and CMA end diastolic and time-averaged mean
      velocities in CB were significantly lower (P < 0.023) than those in severe EA.
      Patterns of renal haemodynamic changes during CB and EA were similar. However,
      the renal patterns differed from those of aortic and gastrointestinal arteries,
      having elevations in vascular resistance indices, a reduction in end diastolic
      velocity and unchanged time-averaged mean velocity. The left renal artery
      resistive index in CB was significantly higher (P < 0.025) than those in EA and
      the physiological state. Renal interlobar artery resistive and pulsatility
      indices in CB were significantly higher (P < 0.016) than those of moderate EA and
      the physiological state. The similar haemodynamic patterns in CB and EA are
      attributable to anaemia, while significant differences may additionally be
      attributed to pathophysiological factors peculiar to CB.

PMID- 16300182
TI  - The pharmacokinetics of diminazene aceturate after intramuscular administration
      in healthy dogs.
AB  - The pharmacokinetics of diminazene aceturate following intramuscular (i.m.)
      administration at 4.2 mg/kg was evaluated in 8 healthy German Shepherd dogs.
      Blood samples were collected at 19 intervals over a period of 21 days. Diminazene
      plasma concentrations were measured using a validated HPLC method with UV
      detection and a sensitivity of 25 ng/ml. The in vitro and in vivo binding of
      diminazene to blood elements was additionally determined. Diminazene
      pharmacokinetics showed a large inter-individual variation after i.m.
      administration. It had a short absorption half-life (K01-HL of 0.11 +/- 0.18 h),
      resulting in a C(max) of 1849 +/- 268.7 ng/ml at T(max) of 0.37 h and a mean
      overall elimination half-life (T1/2beta) of 5.31 +/- 3.89 h. A terminal half-life
      of 27.5 +/- 25.0 h was measured. At 1 h after i.m. injection, 75% of the
      diminazene in whole blood was in the plasma fraction. The results of this study
      indicate that diminazene is rapidly distributed and sequestered into the liver,
      followed by a slower terminal phase during which diminazene is both redistributed
      to the peripheral tissues and/or renally excreted. It is recommended that
      diminazene administered i.m. at 4.2 mg/kg should not be repeated within a 21-day
      period.

PMID- 16300183
TI  - Effects of xylazine, lignocaine and their combination for lumber epidural
      analgesia in water buffalo calves (Bubalus bubalis).
AB  - The study was conducted to evaluate the effects of xylazine alone (0.05 mg/kg),
      lignocaine alone (2.0 mg/kg) and a combination of xylazine and lignocaine (0.05
      mg/kg and 2.0 mg/kg, respectively) after lumbar epidural administration in water
      buffalo calves. Fifteen nondescript, male water buffalo calves of 6-8 months of
      age and weighing between 55 and 75 kg were randomly placed in 3 groups (A, B and
      C). The agents were administered at the 1st lumbar epidural space. Clinico
      physiological parameters such as analgesia, ataxia, sedation, salivation, heart
      rate, respiratory rate and rectal temperature were studied. Other haematological
      and biochemical parameters monitored were haemoglobin, packed cell volume, total
      leukocyte count, plasma glucose, cortisol, protein albumin, globulin, blood urea
      nitrogen, creatinine, ALT, sodium, potassium and chloride. The onset of analgesia
      was faster in group C (3.0 +/- 0.44 min) compared with that of group B (4.4 +/-
      0.40 min) and group A (34.0 +/- 1.86 min). Analgesia of the thorax, flank,
      inguinal region, hind limbs, perineum and tail was complete in group C, but mild
      to moderate in groups A and B. Ataxia was severe in groups B and C and mild in
      group A. Mild to deep sedation were produced by groups A and C animals. Longer
      duration and greater depth of analgesia was produced in animals in group C. Heart
      rate, respiratory rate and rectal temperature decreased in groups A and C. The
      haematological parameters decreased in all the groups. The biochemical parameters
      like glucose, cortisol, blood urea nitrogen, creatinine, ALT increased in all the
      animals. However, total proteins and albumin decreased in the 3 groups. The
      plasma electrolytes sodium, potassium and chloride did not show any significant
      change. The results of this study indicated a possible additive analgesic
      interaction between epidurally administered xylazine and lignocaine, without
      causing any marked systemic effects in water buffalo calves.

PMID- 16300184
TI  - Acute aortic rupture in a dog with spirocercosis following the administration of
      medetomidine.
AB  - Spirocercosis is an emerging disease in veterinary medicine. A strong suspicion
      of spirocercosis is usually evident after a thorough clinical examination and
      radiography of the chest has been performed. Lesions seen on radiography include
      an oesophageal mass, spondylitis and oesophageal air. Unfortunately, radiography
      is not diagnostic and additional diagnostic procedures are required to confirm
      the diagnosis. Endoscopy is commonly performed to diagnose the condition. The dog
      presented in this study had radiographic and clinical signs consistent with
      spirocercosis and definitive diagnosis was required. Shortly after sedation with
      medetomidine, the dog went into cardiac arrest and failed to respond to
      resuscitative measures. On post mortem, the diagnosis of spirocercosis was
      confirmed and the cause of death was identified as acute aortic rupture. Aortic
      aneurysms are not an uncommon finding and cause of acute death in dogs with
      spirocercosis. The acute rupture of the aorta in this case is most probably the
      result of cardiovascular changes associated with the administration of
      medetomidine. Medetomidine causes an acute rise in systemic vascular resistance
      with hypertension. The increase in shear stress across the weakened aortic wall
      resulted in rupture. Caution with the use of medetomidine in patients with
      spirocercosis is advised.

PMID- 16300185
TI  - Caprine vertebral osteomyelitis caused by Rhodococcus equi.
AB  - There have been reports of Rhodococcus equi infections in goats in Australia,
      America and India. In this study, R. equi was isolated from an inflamed vertebra
      in a Boer goat in South Africa. At autopsy, there was a purulent inflammatory
      reaction in the 1st cervical vertebra. Histopathologically, a neutrophilic
      infiltration was encountered in the bone. Aerobic culture of swabs collected from
      the abscesses yielded R. equi in pure culture that was identified on biochemical
      tests. R. equi has become important as the cause of an opportunistic infection in
      people suffering from HIV.

PMID- 16300186
TI  - Lymphangiosarcoma in a 3.5-year-old Bullmastiff bitch with vaginal prolapse,
      primary lymph node fibrosis and other congenital defects.
AB  - Lymphangiosarcoma is an extremely rare tumour in dogs with only 16 cases reported
      in the literature. Lymphoedema, which may be primary due to defects in the
      lymphatic system, or secondary to various other pathologies, often precedes
      malignancy. Of the 16 canine reports, only 1 dog was confirmed as having had
      prior primary lymphoedema due to aplasia of the popliteal lymph nodes. A case of
      lymphangiosarcoma is described in a 3.5-year-old purebred, Bullmastiff bitch
      which presented with vaginal blood 'spotting' for 3 weeks after cessation of
      oestrus, during which intromission by the male had been unsuccessful. During
      ovariohysterectomy a large multicystic, proliferative, spongy, fluid-filled,
      brownish-red mass surrounding the cervix and projecting into the abdominal space
      was removed with the cervix, and a diagnosis of lymphangiosarcoma made on
      histological and electron microscopic examination of the tissue.
      Ultrastructurally, no basement membrane or pericytes were found, only some of the
      neoplastic endothelial cells were linked by tight junctions while there were gaps
      between others, and neither micropinocytotic vesicles nor Weibel-Palade bodies
      occurred in the cells examined. Very few of the endothelial cells lining the many
      interlinking, tortuous maze of channels, stained slightly positive
      immunohistochemically for factor VIII-related antigen. The channels were filled
      mostly with serous fluid, and occasionally mixed leucocytes and some
      erythrocytes. The endothelium was often associated with underlying blocks of
      collagenous material, as well as loosely-arranged aggregates of lymphocytes,
      other mononuclear cells and occasional neutrophils in the connective tissue
      septae and more prominently perivascularly. The bitch was discharged on
      antibiotic treatment but returned 2 weeks later with apparent prolapsed vagina
      which failed to reduce over the next week. Laparotomy revealed the tumour to have
      spread extensively in the caudal abdomen to involve the broad ligament and the
      ventral rectal serosa, and the 'prolapsed' tissue was found to be expanded
      vaginal wall. The bitch was euthanased and necropsied, Histological examination
      confirmed lymphangiosarcomatous invasion of the submucosal and muscular layers of
      the retroperitoneal, traumatised, prolapsed part of the vagina, the urethra and
      the ventral rectal wall. The broad ligament was diffusely invaded with tumour
      which had proliferated into the caudal abdominal space, and 3 small intra
      trabecular foci of tumour were found in the right popliteal lymph node near the
      hilus. Mitotic figures were generally scarce. There was mild subcutaneous oedema
      of the ventral trunk extending from the axillae to the inner proximal thighs,
      which had not been evident clinically, and the lymph nodes (peripheral more so
      than internal) microscopically showed marked trabecular and perivascular fibrosis
      especially in hilar regions. Other congenital defects were hepatic capsular and
      central venous fibrosis with lymphatic duplication and dilatation in all areas of
      connective tissue, ventrally-incongruous half-circular tracheal rings, and
      multifocal renal dysplasia affecting the right kidney. There was locally
      extensive subacute pyelonephritis of the left kidney.

PMID- 16300187
TI  - The role of fluorescence polarization immuno-assay in the diagnosis of plant
      induced cardiac glycoside poisoning livestock in South Africa.
AB  - Poisoning with cardiac glycoside-containing plants is collectively the most
      important plant-associated poisoning of livestock in southern Africa. As a
      diagnosis of this significant poisoning is currently based on circumstantial
      evidence, a practical chemical procedure indicating the presence of cardiac
      glycosides in plants and animal specimens would be of considerable benefit. The
      fluorescence polarization immunoassay (FPIA) method, used to determine digoxin
      plasma levels in humans and dogs, was adapted to estimate cardiac glycoside
      levels in known cardiac-glycoside-containing plants as well as in the rumen and
      organs of dosed sheep. Positive FPIA values were obtained with bufadienolide
      containing plants, while negative results were obtained with plants not known to
      contain cardiac glycosides. The FPIA has aided in the diagnosis of cardiac
      glycoside poisoning in livestock and game in 30 outbreaks examined at the
      Division of Toxicology, Onderstepoort Veterinary Institute. Each outbreak is
      briefly described. As a result of this assay, a better understanding of cardiac
      glycoside poisoning has been reached.

PMID- 16300188
TI  - First report of a field outbreak of the oriental eye-fluke, Philophthalmus gralli
      (Mathis & Leger 1910), in commercially reared ostriches (Struthio camelus) in
      Zimbabwe.
AB  - A total of 17 commercially reared ostriches (Struthio camelus) from Msengi farm,
      Chinhoyi, Zimbabwe, observed with swollen eyes, severe conjunctivitis and
      constant lacrimation accompanied by a purulent exudate, were restrained for
      further clinical examination. Some of the birds were semi-blind with severe loss
      of body condition. When examined, tiny organisms were observed attached to the
      nictitating membranes and the conjuctival sacs of both eyes. The organisms were
      identified as Philophthalmus gralli, the "oriental eye-fluke" and Melanoides
      tuberculata, a prosobranch snail, was confirmed as the intermediate host through
      natural and experimental infection. To the best of our knowledge this is the
      first record of the oriental eye-fluke infection in birds in Zimbabwe and Africa
      and extends its known geographical range.

PMID- 16300189
TI  - Aspects of the ecology of the Asian tapeworm, Bothriocephalus acheilognathi
      Yamaguti, 1934 in yellowfish in the Vaal Dam, South Africa.
AB  - Seasonal surveys were conducted at the Vaal Dam between April 2000 and January
      2001. Twenty smallmouth yellowfish (Labeobarbus aeneus) and 20 largemouth
      yellowfish (Labeobarbus kimberleyensis) were collected with the aid of gill nets.
      Surface water quality variables were included. The cestodes were identified as
      either Bothriocephalus acheilognathi Yamaguti, 1934 or "other cestode spp.". The
      majority (99.8%) of the cestodes found in both yellowfish species were identified
      as B. acheilognathi (Asian tapeworm). The prevalence, mean intensity and
      abundance of B. acheilognathi in both yellowfish species were calculated.
      Ecological parameters including species specificity, seasonality, gender
      specificity and relationships between fish size and the Asian tapeworm prevalence
      were also included. In this study, B. acheilognathi preferred L. kimberleyensis
      over L. aeneus although a low intensity was observed in smallmouth yellowfish.
      Furthermore, the infection (in terms of prevalence, abundance and mean intensity)
      in largemouth yellowfish was markedly higher. Seasonal patterns observed in the
      Asian tapeworm's infection of smallmouth yellowfish are attributed to breeding
      and subsequent feeding patterns of this fish species with relatively high
      infections recorded in winter and spring. For L. kimberleyensis no explanation
      can be given regarding the seasonal patterns observed for the mean intensity and
      abundance of B. acheilognathi. The maximum and minimum mean intensity and
      abundance values in largemouth yellowfish were recorded in autumn and spring,
      respectively. In addition, the prevalence of B. acheilognathi was consistently
      high in all four seasons.

PMID- 16300190
TI  - A study of the pathology and pathogenesis of the myocardial lesions in gousiekte,
      a plant-induced cardiotoxicosis of ruminants.
AB  - Myocardial lesions were studied in sheep in which gousiekte was induced by
      experimental dosage of Pachystigma pygmaeum, Fadogia homblei or Pavetta harborii.
      The single most consistent diagnostic histological feature in 33 animals was
      hypertrophy of myocardial fibres in the subendocardial region. Fibrosis in the
      subendocardial region of the apex or left ventricular wall was often scarce or
      absent in animals with a short latent period, and was not always prominent even
      in sheep with an intermediate or long latent period. The presence or absence of
      fibrosis cannot therefore be used to confirm or exclude gousiekte, particularly
      in cases with shorter latent periods. Light microscopical and ultrastructural
      lesions in sheep with gousiekte correspond to a large extent to changes reported
      in humans with dilated cardiomyopathy of unknown cause. It appears that the
      myocardial lesions in gousiekte represent a final common pathway of cellular
      damage rather than a manifestation of a specific type of heart disease. The
      predilection for hypertrophy of myofibres in the subendocardial region is
      probably related to diminished perfusion that potentiates the primary myocardial
      dysfunction.

PMID- 16300191
TI  - Seroprevalence of Toxoplasma gondii infection in domestic pigs reared under
      different management systems in Zimbabwe.
AB  - Serum samples from 474 domestic pigs (Sus scrofa) from Zimbabwe were tested for
      anti-Toxoplasma gondii IgG antibodies using the indirect fluorescent antibody
      test. The results showed that T. gondii infection is widespread in Zimbabwean
      pigs. Seroprevalence was lowest in fattening pigs from large and small-scale
      commercial farms that practise good hygiene (19.75% of 238) and highest in
      backyard scavenging pigs (35.71% of 70). Only 11.7% (11) of the 127 positive
      samples had titres of > or = 1:400 and nine (81.82%) of these 11 originated from
      pigs reared under poor hygienic conditions. A prevalence of 3.51% was found in
      the same group of fattening pigs using an indirect IgG enzyme-linked
      immunosorbent assay at the single serum dilution of 1:400. The serosurvey shows
      the importance of modern intensive husbandry systems in reducing the prevalences
      of T. gondii infection in domestic pigs.

PMID- 16300192
TI  - Some observations on ticks (Acari: Ixodidae) infesting sheep in River Nile
      Province of Northern Sudan.
AB  - Five species of ixodid ticks were found in a cross-sectional survey in which 200
      sheep were examined for ticks in River Nile Province, Sudan. Hyalomma anatolicum
      anatolicum was the predominant species (73.6%), whereas ticks belonging to the
      Rhipicephalus sanguineus group (14.7%), Rhipicephalus evertsi evertsi (9.1%),
      Rhipicephalus simus (2%) and Hyalomma dromedarii (0.5%) were also found. The mean
      tick load was 11.2 per animal. In a subsequent longitudinal survey ticks were
      collected on a monthly basis from eight sentinel sheep that were introduced into
      the area. It was found that H. a. anatolicum almost disappeared during the hot
      period between April and August, whereas it's highest numbers were present in
      winter between November and February. It is concluded that there is only one
      generation of H. a. anatolicum per year, which may explain the year-round
      appearance of clinical cases of malignant ovine theileriosis indicating endemic
      instability of this disease in River Nile Province.

PMID- 16300193
TI  - A survey of tick control methods used by resource-poor farmers in the Qwa-Qwa
      area of the eastern Free State Province, South Africa.
AB  - A survey conducted in five villages in a resource-poor farming community in Qwa
      Qwa, using the rapid rural appraisal technique and a questionnaire survey, showed
      that a significant proportion of the farmers (84%) use traditional or alternative
      methods to control ectoparasites, while 16% use commercial acaricides (chi2 =
      7.1; P < or = 0.05). Alternative control methods included the use of used engine
      oil, household disinfectant and paraffin. Killing of ticks was the main reason
      for control (40%), with disease control being second (20%). Other reasons given
      for controlling ticks were to prevent damage to teats, to provide animals with a
      clean appearance and to protect hides. Some 40% of farmers were aware of the
      effects of ticks on their animals. There is a need for farmer education that will
      provide information on integrated tick management and its advantages over
      absolute reliance on commercial acaricides.

PMID- 16300194
TI  - Immunization of young chicks using graded dose of wild strain of Eimeria tenella.
AB  - A wild strain of Eimeria tenella was isolated and utilized for immunization
      studies. Its optimal sporulation was attained at room temperature 24-25 degrees C
      after 24-48 h. Two groups of chicks were immunized by dosing a graded dose of
      five oocysts/chick/day for 6 days followed by 50 oocysts/chick/day for 7 days. A
      third group was not immunized and served as a negative control. Immunized chicks
      gained mass at the same rate as unimmunized ones, but when challenged with
      200,000 oocysts/chick, mass gains declined in the unimmunized group. The growth
      rate of immunized chicks was not affected by challenge (P > 0.05). Upon
      challenge, unimmunized chicks produced significantly more oocysts than immunized
      chicks (P < 0.005). Immunized chicks withstood a challenged with 200,000
      oocysts/chick without developing any clinical signs whereas the unimmunized
      chicks developed typical clinical signs of coccidiosis. Unimmunized chicks had
      significantly more severe lesions in the caecum than any other group (P > 0.005)
      and also produced significantly more oocysts than any other group (P > 0.005).

PMID- 16300195
TI  - Small mammals as hosts of immature ixodid ticks.
AB  - Two hundred and twenty-five small mammals belonging to 16 species were examined
      for ticks in Free State, Mpumalanga and Limpopo Provinces, South Africa, and 18
      ixodid tick species, of which two could only be identified to genus level, were
      recovered. Scrub hares, Lepus saxatilis, and Cape hares, Lepus capensis,
      harboured the largest number of tick species. In Free State Province Namaqua rock
      mice, Aethomys namaquensis, and four-striped grass mice, Rhabdomys pumilio, were
      good hosts of the immature stages of Haemaphysalis leachi and Rhipicephalus
      gertrudae, while in Mpumalanga and Limpopo Provinces red veld rats, Aethomys
      chrysophilus, Namaqua rock mice and Natal multimammate mice, Mastomys natalensis
      were good hosts of H. leachi and Rhipicephalus simus. Haemaphysalis leachi was
      the only tick recovered from animals in all three provinces.

PMID- 16300197
TI  - Medicare's new drug plan.

PMID- 16300196
TI  - Beak and feather disease virus haemagglutinating activity using erythrocytes from
      African Grey parrots and Brown-headed parrots.
AB  - Psittacine beak and feather disease (PBFD) is a common viral disease of wild and
      captive psittacine birds characterized by symmetric feather loss and beak
      deformities. The causative agent, beak and feather disease virus (BFDV), is a
      small, circular single-stranded DNA virus that belongs to the genus Circovirus.
      BFDV can be detected by PCR or the use of haemagglutination (HA) and
      haemagglutination inhibition (HI) assays that detect antigen and antibodies
      respectively. Erythrocytes from a limited number of psittacine species of
      Australian origin can be used in these tests. In South Africa, the high cost of
      these birds makes them difficult to obtain for experimental purposes.
      Investigation into the use of erythrocytes from African Grey parrots and Brown
      headed parrots yielded positive results showing the haemagglutinating activity of
      their erythrocytes with purified BFDV obtained from confirmed clinical cases of
      the disease. The HA activity was further confirmed by the demonstration of HI
      using BFDV antiserum from three different African Grey parrots previously exposed
      to the virus and not showing clinical signs of the disease.

PMID- 16300198
TI  - How the plan works.

PMID- 16300199
TI  - How to pick a plan.

PMID- 16300200
TI  - The storm's aftermath. La. hospitals face investigations, closures after Katrina.

PMID- 16300201
TI  - Integration demonstration. The CMS' latest pay-for-performance initiative will
      test the power of integrated delivery systems to alter doc practice patterns.
AB  - Linda Magno of the CMS says the Medicare Health Care Quality Demonstration
      project is one of the agency's boldest initiatives yet. She says the project is a
      chance for providers to "redesign the healthcare system." The project will
      feature "a lot of latitude" in payment and waivers of Medicare provisions. And
      the CMS needs a few good volunteer providers to participate.

PMID- 16300202
TI  - Potential conflicts. Policy group's board members sit on corporate boards.

PMID- 16300203
TI  - IRS turns up the heat. Agency may seek data on compensation, benefits.

PMID- 16300204
TI  - Scrushy charged with bribery Charges involve seat on Alabama CON board.

PMID- 16300205
TI  - Erlanger settles for $40 million. Tenn. system faced federal kickback charges.

PMID- 16300207
TI  - JCAHO rival emerges. New group wants in on accreditation game.

PMID- 16300206
TI  - Blues not interested in Fla. pilot.

PMID- 16300208
TI  - Modern Healthcare rules. Our editorial code of ethics guides our coverage of the
      industry.

PMID- 16300209
TI  - Taking quality to heart. Hospital use variety of approaches to land on 100 top
      cardio roster.

PMID- 16300210
TI  - Moving day. Relocating to a new hospital puts staff's logistics skills to the
      test.

PMID- 16300211
TI  - Support seen for Ore. law. Most docs say assisted-suicide Rx 'legitimate': poll.

PMID- 16300212
TI  - Stem cells: should Washington be involved?

PMID- 16300213
TI  - In-store clinics: should you worry?

PMID- 16300214
TI  - A physician's guide to wage-and-hour law.

PMID- 16300215
TI  - 4 cases that test your malpractice IQ.

PMID- 16300217
TI  - 50 reasons to get an EHR.

PMID- 16300218
TI  - Directing your own end-of-life care.

PMID- 16300216
TI  - Is your code cart ready?

PMID- 16300219
TI  - On my own, on top of the world.

PMID- 16300220
TI  - The earnings freeze. Now it's everybody's problem.

PMID- 16300221
TI  - If your patient sues in small claims court.

PMID- 16300222
TI  - Particle size and composition related to adverse health effects in aged,
      sensitive rats.
AB  - Small increases in concentrations of ambient particulate matter (PM*) have been
      linked to adverse health effects, especially in older people and people with
      preexisting respiratory disease. Some epidemiologic studies have shown the
      association to be stronger with PM less than 2.5 microm in aerodynamic diameter
      (PM2.5) than with PM less than 10 microm in aerodynamic diameter (PM10). Some
      scientists and regulators suggest that 2.5 microm might be an arbitrary cutoff
      and that the effects might be more pronounced for PM less than 0.1 microm in
      aerodynamic diameter (ultrafine PM). Our first aim was to determine the relation
      between size of respirable particles and particle toxicity, as well as the health
      effects of short-term increases (spikes) in particle concentration against
      backgrounds of relatively low or high baseline exposures. Our second aim was to
      determine the effect of spikes in concentration of fine particles (0.7 microm in
      mass median aerodynamic diameter [MMAD]) and ultrafine particles (35 nm in count
      median diameter [CMD]) of disparate composition: vanadium pentoxide (V2O5) and
      carbon black. The relative toxicity of these particles was determined in aged
      rats with mild pulmonary inflammation induced by instilled endotoxin. Our third
      aim was to determine the influence of age (aged vs young adult) on particle
      induced toxicity in these rats.

PMID- 16300223
TI  - Importance of understanding pharmacokinetic/pharmacodynamic principles in the
      emergence of resistances, including community-associated Staphylococcus aureus.
AB  - Pharmacologic parameters have been defined to predict efficacy in antimicrobial
      selection for the treatment of uncomplicated skin and skin structure infections
      (uSSSIs). Pharmacokinetics (PK) and pharmacodynamics (PD) are the bases for
      describing the in vivo behavior of antimicrobial agents. T>MIC is the duration of
      time that a pathogen is exposed to concentrations of antimicrobial agents that
      exceed the MIC of that particular organism. For antimicrobials with time
      dependent activity (eg, penicillin and cephalosporins), the T>MIC needed to
      eradicate bacteria is generally 40% to 50% of the dosing interval. The most
      frequently prescribed oral antimicrobials for uSSSI are oral cephalosporins,
      amoxicillin/clavulanic acid, macrolides, anti-staphylococcal penicillins, and
      fluoroquinolones. The selected oral agent should display a broad spectrum of
      antimicrobial coverage, be able to be dosed once, or at most twice, a day, and
      show high levels of target attainment (> or = 90%) for eradicating the key
      pathogens associated with uSSSI. The recent emergence of methicillin-resistant
      Staphylococcus aureus (MRSA) in the community setting (CA-MRSA) is especially
      troublesome in that oral cephalosporins (and all other beta-lactam agents) are
      contraindicated, requiring alternative therapeutic approaches. While a common
      cause of cutaneous disease, including abscess formation, CA-MRSA has caused life
      threatening necrotizing fasciitis and pneumonia. Treatment of abscesses produced
      by this pathogen consists of incision and drainage followed by an appropriate
      oral antimicrobial, based upon knowledge on the local resistance prevalence rates
      or as directed by culture and susceptibility testing.

PMID- 16300224
TI  - Update on treating uncomplicated skin and skin structure infections.
AB  - Dermatologists treat a variety of uncomplicated skin and skin structure
      infections (uSSSIs) such as folliculitis, impetigo, erysipelas, cellulitis,
      furuncles, carbuncles, and non-perirectal abscesses. Most uSSSIs are caused by
      Staphylococcus aureus and Streptococcus pyogenes. The new extended-spectrum
      cephalosporins (cefdinir, cefpodoxime) offer efficacy against most Gram-positive
      and Gram-negative pathogens. Despite recently published guidelines, many
      physicians do not prescribe cephalosporins for uSSSIs out of concern that these
      agents will produce a hypersensitivity reaction in patients allergic to
      penicillin. Although the rate of cephalosporin reaction in penicillin-allergic
      patients is often quoted as up to 10%, this rate does not take into account the
      1% to 3% risk for allergy to cephalosporin alone and the nonspecific increased
      risk of penicillin-allergic patients to develop hypersensitivity to other drugs.
      When these additional risks are considered, the likelihood of a reaction in known
      penicillin-allergic patients, especially to most third-generation and extended
      spectrum cephalosporins, becomes less than 1%. Cephalosporins with side chains
      unlike those of penicillin or ampicillin side chains are less likely to result in
      an allergic reaction in penicillin or ampicillin-allergic patients than
      cephalosporins with similar side chains. Although both cefdinir and cefpodoxime
      are considered to carry a very low risk of cross reactivity with penicillin or
      ampicillin, the former demonstrates better activity against S. aureus. Among the
      late-generation cephalosporins, cefdinir is the most potent oral agent when
      tested against oxacillin-susceptible staphylococci, 4- to 16-fold more active
      than cefprozil and cephalexin, respectively.

PMID- 16300225
TI  - Optimal antibacterial treatment of uncomplicated skin and skin structure
      infections: applying a novel treatment algorithm.
AB  - Incision and drainage combined with antibiotic therapies form the backbone of
      managing uncomplicated skin and skin structure infections (uSSSIs). An algorithm
      has been developed to guide the treatment of uSSSIs in the primary care setting
      in situations where initial empiric therapy is appropriate. This includes
      instances when a culture is taken, but it is deemed appropriate to begin an
      antibiotic empirically pending the results of the culture. The panel that
      developed the algorithm was chaired by Dr. Richard Scher of Columbia University
      and included thought leaders in the fields of clinical dermatology, dermatologic
      surgery, infectious disease, pediatric infectious disease, podiatry, and HIV
      infection. The panel acknowledged that the initial choice of antibiotic is
      generally determined by tolerability, ease of administration, cost, and efficacy.
      The usual choices for initial empiric therapy include cephalosporins,
      penicillinase-resistant penicillins, and beta-lactam/beta-lactamase inhibitor
      combinations. Currently marketed cephalosporins, penicillinase-resistant
      penicillins, and beta-lactam/beta-lactamase inhibitor combinations lack activity
      against methicillin-resistant Staphylococcus aureus (MRSA), and the increasing
      prevalence of community-acquired MRSA (CA-MRSA) was a major consideration when
      designing the treatment algorithm. Many CA-MRSA skin infections present as
      abscess, and drainage is the most important component of therapy in this setting.
      When the history and physical exam suggest CA-MRSA infection, and there is no
      fluctuant collection of purulent material to be drained, a sulfa drug or
      tetracycline is generally the best choice for initial empiric therapy.

PMID- 16300226
TI  - Prophylaxis for and treatment of uncomplicated skin and skin structure infections
      in laser and cosmetic surgery.
AB  - Complications of laser resurfacing include infections, scarring,
      hyperpigmentation, hypopigmentation, and delayed healing. Postoperative
      infections cause pain, prolonged healing, and can result in scarring. Ablative
      laser techniques cause partial- or full-thickness wounds, whereas so-called
      "nonablative procedures" may cause "spotty" epidermal wounds. Antibiotic
      prophylaxis is necessary when the risk for postoperative infection is significant
      or when the risk of infection is moderate but the consequences of infection are
      significant. Prophylactic antibiotic agents should have a broad spectrum of
      activity, be well-tolerated and be safe. The most appropriate choice is a broad
      spectrum agent such as cefdinir, even for patients allergic to penicillin.
      Additionally, all patients should be treated prospectively with antivirals to
      prevent activation and dissemination of herpes simplex virus type I. Treatment of
      infections in patients who have and have not received prophylactic antibiotics
      requires identification of the causative factor and appropriate treatment.
      Nonablative treatments such as photodynamic therapy do not usually require
      antibiotic prophylaxis, although a few patients treated for acne may acquire a
      secondary bacterial infection that should be treated.

PMID- 16300227
TI  - Treatment of uncomplicated skin and skin structure infections in the diabetic
      patient.
AB  - Diabetic neuropathy can lead to the development of ulcers on the lower
      extremities. Prompt treatment lowers the likelihood of infection and reduces the
      probability that an established infection will lead to amputation. Antibiotics
      are selected on the basis of the suspected organism and the level of infection.
      Unnecessary antibiotic prophylaxis is discouraged because it increases the
      likelihood that bacterial resistance to the antibiotic agent will develop.
      Culture samples must be taken by curettage of biopsy rather than by swabbing to
      assure detection of pathogens.

PMID- 16300228
TI  - Treatment of uncomplicated skin and skin infections in the pediatric and
      adolescent patient populations.
AB  - Before 1980, superficial pyodermas in the US were caused primarily by
      streptococci. Studies conducted in Miami show that during the early 1980s, the
      predominant pathogen associated with impetigo in pediatric patients shifted from
      Streptococcus pyogenes to Staphylococcus aureus. Subsequent reports revealed a
      trend of increasing resistance of S. aureus to penicillins. By regular monitoring
      of local sensitivity patterns physicians are more likely to select the
      appropriate antibiotic. The current recommendation for the treatment of pediatric
      skin disease is cephalosporins due to their low likelihood of resistance by S.
      aureus.

PMID- 16300229
TI  - Perioperative use of antibiotics: preventing and treating perioperative
      infections.
AB  - Prevention of postoperative wound infection in dermatologic surgery and
      appropriate use of antibiotics to prevent endocarditis and joint-replacement
      infections are controversial issues. Dermatologists often may misunderstand the
      use of antibiotics to prevent endocarditis, surgical site infections, and
      prosthesis infections. In order to prevent endocarditis associated with surgical
      procedures, the American Heart Association (AHA) has developed clinical practice
      guidelines that apply to surgical patients with prosthetic cardiac valves,
      previous bacterial endocarditis, mitral valve prolapse with valvular
      regurgitation, or thickened leaflets. For these patients, the AHA recommends that
      antistaphylococcal antibiotics (eg, cephalosporins) be given before surgery only
      when the procedure involves significant risk of bacteremia (eg, incision into
      infected tissues). Routine dermatologic surgery of intact skin with sterile
      technique usually does not require prophylaxis. Antibiotic prophylaxis may also
      be justified in surgical patients who are at moderate to high risk for wound site
      infection. Patients should be given prophylactic antibiotics shortly before
      surgery or as soon as the risk is recognized. In patients allergic to penicillin,
      cross reactions are unlikely for most second- and third-generation agents
      (cefdinir, cefuroxime, cefixime, ceftibuten), because these agents lack a side
      chain similar to penicillin. By identifying the risk of infection, being aware of
      the risks of antibiotic therapy, and weighing the risks and benefits of each
      option, dermatologists can devise individualized treatments, thus optimizing
      outcomes of their patients.

PMID- 16300230
TI  - A comprehensive approach to dentistry.

PMID- 16300231
TI  - Toothbrush abrasions and noncarious cervical lesions: evolving concepts.
AB  - Toothbrush abrasion at the cervical areas of teeth is generally thought to be a
      result of frequent or forceful toothbrushing, faulty or vigorous technique,
      filament stiffness or design, dominant hand dexterity, or abrasive dentifrices.
      However, a review of the evidence-based literature cannot conclusively establish
      any one factor as the primary etiology of cervical abrasions because of inherent
      methodological limitations and conflicting results. Rather, a variety of factors
      related to toothbrushing may act in concert with dental erosion and, possibly,
      occlusal loading in the creation of noncarious cervical lesions. Individual
      variation also may make some individuals more susceptible to development and may
      modify the progression of those lesions. Individual variations may involve oral
      and dental anatomy, periodontal status or phenotype, and periodontal disease
      history and treatment. Further research is needed to clearly assess the
      interaction of all those factors in the development of cervical lesions.
      Therefore, awareness of a multifactorial etiology in noncarious cervical lesions
      may help the clinician to formulate an appropriate treatment plan for the
      patient.

PMID- 16300232
TI  - Impression material selection in contemporary fixed prosthodontics: technique,
      rationale, and indications.

PMID- 16300233
TI  - Conservative adjunct to esthetic orthodontic treatment in young patients.
AB  - The esthetic effect of orthodontic treatment in young patients may sometimes be
      incomplete without performing additional procedures related to the form and
      texture of the anterior teeth. Six young patients, aged 7 to 21 years, presented
      for orthodontic treatment to improve their dental esthetics. The problems of
      tooth staining, mutilation, congenitally missing teeth, tooth size/arch length
      discrepancy, and sequellae of dental trauma neccessitated a combined orthodontic
      prosthodontic treatment. Changing morphology and texture by conservative
      prosthetic procedures proved to be a successful complement to orthodontic
      treatment.

PMID- 16300234
TI  - The video game generation is now in dental school.

PMID- 16300235
TI  - Three-dimensional software for fabrication of a surgical template and final
      implant-supported restoration for a fully edentulous maxilla: a case report.

PMID- 16300236
TI  - Avian influenza: the next respiratory disease pandemic?

PMID- 16300237
TI  - The controlled placement and delayed polymerization technique for the direct
      Class 2 posterior composite restoration.
AB  - Adhesion dentistry and its application to the direct posterior composite
      restoration is the most controversial topic in dentistry today. The concepts
      behind this procedure are now the backbone of restorative dentistry. Adhesion
      dentistry influences basic fillings, crown buildups, post-and-core restorations,
      cementation, orthodontics, and endodontics. Yet, controversy remains about the
      correct way to place a direct Class 2 posterior composite restoration. This
      article will examine the scientific evidence to determine which materials and
      placement techniques will achieve the optimum direct Class 2 posterior composite
      restoration at or below the cementoenamel junction using the controlled placement
      and delayed polymerization technique.

PMID- 16300238
TI  - Hospitals can't prepare for disaster without better government help.

PMID- 16300239
TI  - Where doth your data go? Creating good data means more efficiency and even more
      savings.

PMID- 16300240
TI  - Prepared to deliver a helping hand.

PMID- 16300241
TI  - Getting smart about safe infusion pump options.

PMID- 16300242
TI  - A matter of reprocessing.

PMID- 16300243
TI  - A touch of technology begets big savings.

PMID- 16300244
TI  - Old CHeS bylaws are bygone. Changes mean more voting members.

PMID- 16300245
TI  - Covering the cost of linens.

PMID- 16300246
TI  - The value of cleansing data.

PMID- 16300247
TI  - Form and function.

PMID- 16300248
TI  - Sometimes, the relationship just doesn't work.

PMID- 16300249
TI  - Hired guns add to lawsuit costs.

PMID- 16300250
TI  - Let's get real!

PMID- 16300251
TI  - Restoring the incisal edge.
AB  - Restorative dentistry evolves with each development of new material and
      innovative technique. Selection of improved restorative materials that simulate
      the physical properties and other characteristics of natural teeth, in
      combination with restorative techniques such as the proximal adaptation and
      incremental layering, provide the framework that ensures the optimal development
      of an esthetic restoration. These advanced placement techniques offer benefits
      such as enhanced chromatic integration, polychromatism, ideal anatomical form and
      function, optimal proximal contact, improved marginal integrity and longer
      lasting directly placed composite restorations. The purpose of this article is to
      give the reader a better understanding of the complex restorative challenge in
      achieving true harmonization of the primary parameters in esthetics (that is,
      color, shape and texture) represented by the replacement of a single anterior
      tooth. The case presented demonstrates the restoration of a Class IV fracture
      integrating basic adhesive principles with these placement techniques and a
      recently developed nanoparticle hybrid composite resin system (Premise,
      Kerr/Sybron, Orange, CA). The clinical presentation describes preoperative
      considerations, tooth preparation, development of the body layer, internal
      characterization with tints, development of the artificial enamel layer, shaping
      and contouring, and polishing of a Class IV composite restoration. The clinical
      significance is that anterior tooth fractures can be predictably restored using
      contemporary small particle hybrid composite resin systems with the
      aforementioned restorative techniques. These placement techniques when used with
      proper attention to preparation design, adhesive protocol and finishing and
      polishing procedures, allow the clinician to successfully restore form, function
      and esthetics to the single anterior tooth replacement.

PMID- 16300252
TI  - The unilateral posterior functional crossbite: an opportunity to restore form and
      function.
AB  - The unilateral posterior crossbite (UPXB) with functional shift of the mandible
      is commonly encountered in young children and adolescents. Differential diagnosis
      and the impact this type of malocclusion might have upon the growth and
      development of dental and facial components are discussed. Impaired function and
      compromised facial esthetics may be consequences of untreated UPXBs with
      functional shifts. Appropriate treatment protocols and specific orthodontic
      appliances intended to correct these problems are presented.

PMID- 16300253
TI  - Tongue piercing as risk factor to periodontal health.
AB  - Body piercing has grown in popularity among teenagers and young adults. Dating
      back to antiquity, piercing is a cultural practice used in ceremonial or
      religious rites; however, today, it is commonly exercised as a method of self
      expression. Different complications and side effects are associated with
      intraoral piercing, including pain, swelling, infection, gingival trauma, chipped
      or fractured teeth, increased salivary flow, calculus buildup, and interference
      with speech and swallowing. We present a case report of periodontal treatment of
      traumatized gingival tissue caused by a tongue stud. The step-by-step periodontal
      surgical management of the case has been elaborated. The role of oral and dental
      health care professionals in managing the growing problem of tongue piercing as a
      periodontal risk factor has also been highlighted.

PMID- 16300254
TI  - Use of interdisciplinary team approach in establishing esthetic restorative
      dentistry.
AB  - Managing crown lengthening in cases of attrition (wear or loss of tooth
      substance) and achieving desired esthetic outcomes, especially in the esthetic
      zone, is challenging. This case report presents an interdisciplinary approach to
      case management. Concomitant use of digital imaging, along with model wax-ups and
      surgical guide, were used to enhance patient acceptance during treatment planning
      and to facilitate communication and treatment implementation among dental
      professionals and laboratory technicians. Resulting surgical template was used
      for crown lengthening to apically position the gingival zenith (margin) to a
      predetermined level, crown preps and final restorations, respectively, ultimately
      improving esthetics and patient satisfaction. Supplementing esthetic treatment
      planning with digital imaging, model wax-ups and a surgical template allows a
      dentist to carry information into the mouth and incorporate it into the surgical
      procedure, crown preps, temps and, ultimately, the final restoration.

PMID- 16300255
TI  - Soft tissue plasmacytosis. A case report.
AB  - Plasma cell gingivitis was identified during the early 1970s as an allergic
      reaction to a component in a chewing gum. The clinical picture was described as
      bright erythema of the entire gingiva, loss of stippling and generalized
      swelling. Today, many allergens appear to be responsible for this problem. This
      report presents an unusual case of soft-tissue plasmacytosis in a totally
      edentulous patient, which may have been related to the use of a household and
      kitchen cleaning solution on the prostheses.

PMID- 16300257
TI  - Average salary of OR directors tops $90,000; raises pace inflation.

PMID- 16300256
TI  - Hospital dentistry and GPRs. A relationship with a past.
AB  - Dental programs have evolved from an occasional component of hospitals to fully
      recognized departments within the structure of most institutions. A review is
      presented of some of these developments, including the initiation of general
      practice residency (GPR) programs and training in a residency program as a
      substitute for the standard licensing examination.

PMID- 16300258
TI  - Generators, strong teams helped ORs stay open during gulf disaster.

PMID- 16300259
TI  - Finding a 'silver lining' in management.

PMID- 16300260
TI  - Despite pressures, managers find rewards.

PMID- 16300261
TI  - What's needed to mentor new leaders?

PMID- 16300262
TI  - Are your OR's warming cabinets too hot?

PMID- 16300263
TI  - Hospital focuses on recruiting new grads.

PMID- 16300264
TI  - ASC managers earn less but more satisfied.

PMID- 16300265
TI  - ASCs voice concerns to CMS on Medicare reimbursement.

PMID- 16300266
TI  - A contemporary overview of encapsulating peritoneal sclerosis in Japan.

PMID- 16300267
TI  - A historical review of encapsulating peritoneal sclerosis.
AB  - Publications providing insights into the pathophysiology of, and therapeutic
      strategies for, EPS are the focus of the present review. Referenced publications
      are limited to those written in English.

PMID- 16300268
TI  - Epidemiology of encapsulating peritoneal sclerosis in Japan.
AB  - Since the first peritoneal dialysis (PD) patients with encapsulating peritoneal
      sclerosis (EPS) were reported in 1980, EPS has been considered primarily a fatal
      complication. The incidence of EPS in PD patients has been reported to range from
      0.7% to 7.3%, and the rate appears to be higherin patients receiving long-term
      treatment. The most recent data from Japan show an overall incidence of 2.5%,
      with a clear impact of extended PD duration, which also augments mortality. The
      incidence increases and the prognosis worsens with longer durations of PD. The
      incidences (and mortality rates) for EPS were 0% (0%), 0.7% (0%), 2.1% (8.3%),
      5.9% (28.6%), 5.8% (61.5%), and 17.2% (100%) for patients who had undergone PD
      for 3, 5, 8, 10, 15, and >15 years respectively. Because EPS occurs after
      withdrawal from PD in more than half of patients with the condition, strict
      monitoring is necessary when a long-term patient is withdrawn from PD.
      Maintaining patients on standard PD for more than 8 years using conventional
      solutions is associated with a substantial risk for the development of EPS.

PMID- 16300269
TI  - Pathology of encapsulating peritoneal sclerosis.
AB  - Pathology findings of encapsulating peritoneal sclerosis (EPS) are reviewed to
      establish histologic criteria for a diagnosis of EPS. The typical macroscopic
      finding is a cocoon-like encapsulation of the entire intestine. This
      encapsulation is frequently accompanied by fibrin deposition, focal bleeding on
      the peritoneum, and various quantities of bloody ascites. A thin membrane on the
      visceral peritoneum contributes to the formation of the intestinal encapsulation.
      Histologically, the membrane is composed mainly of organized fibrin, probably
      derived from plasma exudation from the peritoneal microvasculature. Peritoneal
      fibroblasts appear swollen and exhibit an increased level of cellularity,
      accompanied by expression of various activation and proliferation markers.
      According to the "two-hit" theory of EPS pathogenesis, deterioration of the
      peritoneum as a result of the peritoneal dialysis (PD) procedure (the first
      "hit") and superimposition of inflammatory stimuli such as infectious peritonitis
      (the second "hit") are thought to play key roles in the pathogenesis of EPS.
      Based on histologic examination of peritoneal biopsy specimens, the detection of
      fibrin deposition and fibroblast phenotypic alteration were proposed as important
      findings for early diagnosis of EPS. Persistent inflammatory changes are also
      predictive of the future onset of EPS. Careful histologic evaluation of
      peritoneal biopsy specimens, combined with Laparoscopic observations after
      withdrawal of PD, is required for the early diagnosis and treatment of EPS.

PMID- 16300270
TI  - Encapsulating peritoneal sclerosis--a clinician's approach to diagnosis and
      medical treatment.
AB  - Encapsulating peritoneal sclerosis (EPS) is recognized as a serious complication
      of continuous peritoneal dialysis. A preliminary diagnosis of EPSis usually based
      on clinical signs and symptoms, which commonly include abdominal pain, nausea,
      vomiting, anorexia, abdominal fullness, an abdominal mass, bowel obstruction, and
      radiologic findings, including abdominal roentgenogram, contrast studies,
      ultrasound studies, and computed tomography. The diagnosis is confirmed by
      laparoscopy or laparotomy showing the characteristic gross thickening of the
      peritoneum enclosing some or all of the small intestine in a cocoon of opaque
      tissue. A variety of therapeutic approaches to EPS have been reported. This
      review discusses medical treatment of EPS and includes an overview of the
      clinical features and diagnostic aspects of the condition.

PMID- 16300271
TI  - Successful surgical management of encapsulating peritoneal sclerosis.
AB  - BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a serious complication of
      long-term peritoneal dialysis (PD). The mortality rate for EPS has been high,
      primarily because of complications related to bowel obstruction. Also,
      therapeutic guidelines for EPS have not yet been established. In our hospital,
      favorable postoperative results were obtained in 50 patients whose EPS was
      treated surgically. PATIENTS: All patients had chronic glomerulonephritis as the
      underlying kidney disease. All had undergone PD for between 29 months and 220
      months (average: 113.9 months). During the course of PD, 3 patients developed EPS
      and were subsequently transferred to hemodialysis (HD). The other 47 patients
      (94.0%) developed EPS after discontinuation of PD. The reasons for transfer to HD
      were inadequate ultrafiltration (26 patients), bacterial peritonitis (16
      patients), hypoalbuminemia (2 patients), renal transplantation (3 patients), and
      occurrence of EPS (3 patients). INTERVENTION: At laparotomy, a definitive
      diagnosis of EPS was established in all patients by the presence of clumped
      intestine cocooned with a dense sclerotic membrane. In all cases, the small
      intestine was completely released by ablation of the capsules, resulting in
      resolution of the bowel obstruction symptoms. In 5 patients, the large intestine
      was ablated solely at the region of the sigmoid colon. The operating time varied
      from 3 hours to 18 hours (average: 6.9 hours). Oral food intake was initiated 5 -
      60 days (average: 10.2 days) after surgery. RESULTS: Perforation of the small
      intestine was detected postoperatively in 2 patients, who died 26 days and 37
      days after surgery. The remaining 48 patients were followed for between 9 months
      and 107 months (average: 34.6 months). During follow-up, 6 - 12 months after the
      initial surgery, 4 patients experienced a recurrence of bowel obstruction
      symptoms that required a second laparotomy with enterolysis. Excluding the 2
      patients with fatal outcomes, 46 patients (96%) experienced complete relief from
      bowel obstruction symptoms. The remaining 2 patients continued to experience
      mild, sub-acute bowel obstruction symptoms that could be successfully controlled
      solely by diet. CONCLUSIONS: Surgical treatment of 50 patients with EPS produced
      successful outcomes in all but 2 patients (96% success). Encapsulating peritoneal
      sclerosis should be actively treated by surgeons who genuinely understand this
      pathologic condition.

PMID- 16300272
TI  - The role of peritoneal fibrosis in encapsulating peritoneal sclerosis.
AB  - Encapsulating peritoneal sclerosis (EPS) is a serious complication of long-term
      continuous peritoneal dialysis therapy. The progression of EPS has been
      classified into four stages by Kawanishi and colleagues: pre-EPS, and the
      inflammatory, encapsulating, and ileus stages. The key issue is how to diagnose
      EPS early enough to allow for curative treatment. In this article, we review the
      mechanisms of peritoneal fibrosis, especially from the perspective of collagen
      synthesis, and the potential role of that fibrosis in the pathogenesis of EPS.

PMID- 16300273
TI  - Experimental animal models of encapsulating peritoneal sclerosis.
AB  - Encapsulating peritoneal sclerosis (EPS) is an infrequent, but extremely serious
      complication of long-term peritoneal dialysis. The cause of EPS is unclear, but
      the low incidence suggests that it is most likely multifactorial. The elucidation
      of developmental pathways and predictive markers of EPS would facilitate the
      identification and management of high-risk patients. Animal models are often used
      to define pathways of disease progression and to test strategies for treatment
      and prevention in the patient population. Ideally such models could help to
      define the cause of EPS and its developmental pathways, to facilitate the
      identification of contributing factors and predictive markers, and to provide a
      system to test therapeutic strategies. Researchers have studied several rodent
      models of EPS that rely on chronic chemical irritation (for example, bleach, low
      pH solution, chlorhexidine gluconate) to induce peritoneal sclerosis and
      abdominal encapsulation. Development in all models is progressive, with
      inflammation giving way to peritoneal fibrosis or sclerosis with accumulating
      membrane damage, culminating in cocoon formation. Microscopic findings are
      similar to those proposed as diagnostic criteria for clinical EPS: an initial
      inflammatory infiltrate and submesothelial thickening, collagen deposition, and
      activation and proliferation of peritoneal fibroblasts. The potential to block
      progression of peritoneal sclerosis in these models by anti-inflammatory,
      antifibrotic, and anti-angiogenic agents, and by inhibitors of the renin
      angiotensin system have been demonstrated. Animal models based on clinically
      relevant risk factors (for example, uremia, peritonitis, and long-term exposure
      to dialysis solutions) now represent the next step in model development.

PMID- 16300274
TI  - Is normal saline harmful to the peritoneum?
AB  - BACKGROUND: Normal saline (0.9% NaCl) is used during various abdominal surgical
      interventions and during peritoneal dialysis to rinse the peritoneal cavity.
      Although no clear clinical evidence exists for the bioincompatibility of normal
      saline, various experimental studies have suggested that 0.9% NaCl solution can
      initiate fibrosis of peritoneum. MATERIAL AND METHODS: We review the data derived
      from in vitro and in vivo experimental studies demonstrating the cytotoxic effect
      of 0.9% NaCl and its ability to initiate peritoneal adhesions. RESULTS: Normal
      saline reduces the viability and fibrinolytic activity of peritoneal mesothelial
      cells. Use of normal saline to wash the peritoneal cavity during abdominal
      operations or after chronic peritoneal dialysis is more likely to produce
      adhesions than is no irrigation at all. Chronic exposure of the peritoneum to
      normal saline causes overgrowth of the connective tissue and formation of new
      blood vessels within that tissue. CONCLUSION: Normal saline is a bioincompatible
      solution that predisposes to the formation of peritoneal adhesions and fibrosis
      of the peritoneum. A 0.9% NaCl solution should therefore not be used to rinse the
      peritoneal cavity after interruption of peritoneal dialysis.

PMID- 16300275
TI  - The plasma leak-to-response hypothesis: a working hypothesis on the pathogenesis
      of encapsulating peritoneal sclerosis after long-term peritoneal dialysis
      treatment.
AB  - Encapsulating peritoneal sclerosis (EPS) is one of the most serious complications
      of long-term peritoneal dialysis (PD). Long-term PD therapy has been suggested as
      a risk factor for EPS development among patients in Japan and Australia. Although
      the primary mechanism of EPS development has not been clarified, histologic
      changes of the peritoneum associated with prolonged PD are postulated to be
      causally related. The present article proposes a working hypothesis--the plasma
      leak-to-response hypothesis--that vascular alterations in the peritoneum of long
      term PD patients play a crucial role in the initiation and development of EPS.

PMID- 16300276
TI  - Peritoneal dialysis in Japan: the issue of encapsulating peritoneal sclerosis and
      future challenges.
AB  - Encapsulating peritoneal sclerosis (EPS) is a life-threatening complication of
      peritoneal dialysis (PD). The overall prevalence of EPS in Japanese PD patients
      is 2.3%. Among patients on PD for less than 5 years, the rate is 0.9%; among
      patients on PD for 5 - 10 years, the rate is 3.8%; and among patients on PD for
      >10 years, it is 11.5%. Thus, the longer the treatment duration, the higher the
      prevalence of EPS. Encapsulating peritoneal sclerosis does not result solely from
      the natural progression of peritoneal sclerosis. A "second hit" event, such as
      bacterial peritonitis, abdominal bleeding, or abdominal surgery may be needed to
      trigger the onset of EPS in the face of advanced peritoneal sclerosis. To prevent
      development of EPS, PD treatment is replaced by other treatments when patients
      reached high-transport status. Peritoneal lavage and prednisolone administration
      have been reported to be effective in preventing or stopping the progress of EPS.
      When bowel obstruction has occurred, total enterolysis to remove the fibrous
      capsule from the bowel is indicated. To maximize overall quality of life,
      patients with endstage renal disease (ESRD) should have the choice to make use of
      all the treatment modalities available: PD, hemodialysis (HD), and
      transplantation. Furthermore, the development of truly biocompatible PD equipment
      -including peritoneal catheters, solutions, and systems--are desirable to extend
      PD treatment for the long-term. The cost of individual products could decrease
      significantly if PD use were to increase to 30% from 10% among ESRD patients
      worldwide. As practitioners, we have to further improve the technical survival
      rate and functional duration of PD treatment so that adequate peritoneal function
      can be maintained for 10 years in at least 40% of PD patients. The goal is to
      place PD on par with HD using high-flux dialysis membranes and ultrapure dialysis
      solution.

PMID- 16300278
TI  - [The Vaud-Geneva collaboration in Otorhinolaryngology Service].

PMID- 16300277
TI  - Recommendations on the management of encapsulating peritoneal sclerosis in Japan,
      2005: diagnosis, predictive markers, treatment, and preventive measures.
AB  - This comprehensive update on the management of encapsulating peritoneal sclerosis
      incorporates insights gained from recently published findings and the accumulated
      experience of the authors. Aspects covered include diagnosis, risk factors and
      predictive markers, treatment, and prevention, including criteria for withdrawal
      from peritoneal dialysis.

PMID- 16300279
TI  - [Indications for tonsillectomy in 2005].
AB  - Tonsillectomy is one of the most frequent ENT operations but yet a very disputed
      one. The majority of children and adults are treated for recurrent angina, which
      is validated by several clinical trials. For an adult a peritonsillar abscess is
      best treated by immediate tonsillectomy. Incision and drainage is a validated
      method as well, as long as there is no indication to a delayed tonsillectomy. The
      tonsillectomy alone is not a validated treatment for adult upper airway
      obstruction. On the other hand it is a recommended procedure for children upper
      airway obstruction. Partial tonsillectomy (tonsillotomy) is also a validated
      procedure for this indication. Finally the peritonsillar abscess in a child
      should first be treated by one or two days of intravenous antibiotics.

PMID- 16300280
TI  - [Chronic tinnitus].
AB  - Chronic tinnitus is a frequent symptom in the current medical practice. Patients
      presenting with chronic tinnitus have to be evaluated by comprehensive
      examination, including ENT status, audiometry and complete neuro-otological
      evaluation if required, to exclude an organic cause of tinnitus, as an external-
      or middle ear lesion, or a retro-cochlear process. Most often, chronic tinnitus
      is only associated with a sensorineural hearing-loss. Overall, no drug treatment
      can be proposed. However, the patient needs help and two techniques can be
      proposed to make the symptom more tolerable: the bio-psycho-social model, with a
      medical and psychological sustain, and the habituation auditory therapy, using
      noisers to mask the tinnitus.

PMID- 16300281
TI  - [Endoscopic mucosal resection for the treatment of superficial adenocarcinima
      developed on the Barrett's mucosa].
AB  - We present a new technique of endoscopic mucosal resection for the treatment of
      extended superficial lesions of the esophagus such as early squamous cell
      carcinoma, high grade intraepithelial neoplasia or early adenocarcinoma arising
      in Barrett's esophagus. A modified rigid esophagoscope has been designed. A large
      mucosal area is sucked against a perforated 180 degrees window. Mucosal resection
      is performed by an electrical wire loop at a constant depth of 1 +/- 0,1 mm. The
      resected surface varies from 4 to 12 cm2. Circumferential resection consists of
      two opposite hemi-circumferential resections. The resection yields one or two
      specimens only for histological study allowing easy orientation and analysis of
      the resection margins. The deep resection margin is precisely located at the
      submucosal level, a prerequisite for a safe resection of T1a cancers.

PMID- 16300282
TI  - [Neurogenic inflammation and chronic rhinosinusitis].
AB  - The nasal mucosa is one of the anatomical region which have the highest density
      of sensory innervation. The function of this sensory innervation is probably
      linked to the protection of the lower airways against inhalation of airborne
      particles and potentially harmful substances. Chronic rhinosinusitis (CRS) is
      associated with nasal obstruction, rhinorrhea, loss of sense of smell and facial
      pain or headaches. When allergy or specific hyperreactivity, infection, systemic
      or genetic deseases have been excluded, the diagnosis of non specific
      hyperreactivity or neurogenic inflammation is proposed. Sensory neuropeptides
      released by sensory nerves endings have powerful proinflammatory effects. The
      best treatment yet available include nasal lavages and the local application of
      topical corticosteroid spray.

PMID- 16300283
TI  - [The tuberculosis of the ear: a report of two cases].
AB  - The tuberculosis of the ear is rare. In most cases, the clinical picture
      resembles that of a chronic otitis media. The bacteriological exams are seldom
      positive at the earliest stage of the disease. The two reported cases of this
      paper illustrate the difficulties of the diagnosis. In the first one, the
      diagnosis was made although the bacteriological proof could not be obtained,
      based on other exams. In the second one, it was made on the basis of a positive
      PCR of the tissues removed during a radical mastoidectomy. The literature on the
      various clinical aspects of the tuberculosis of the ear is reviewed.

PMID- 16300284
TI  - [True or false vertigo: a true or false question?].
AB  - Some practitioners ask on which criteria vertigo can be considered as "true" or
      "false". The goal of this paper is to explain why such a concept is misleading.
      Vertigo and imbalance are subjective symptoms caused by many possible factors,
      somatic or psychologic, which may cause, in turn, psychological distress in some
      patients. In all cases, the complain is "true", even in case of psychological
      disorder. To evaluate patients suffering from vertigo, knowledge in anatomy and
      physiology are necessary as well as knowledge of the interface between neuro
      totologic and psychiatric conditions.

PMID- 16300285
TI  - [Supportive care in oncology: a concept of rehabilitation].
AB  - The prevalence and prognosis of cancer are changing. The number of diagnosed
      cancers is rising in Western countries. These diseases often become chronic
      illnesses and necessitate major efforts of adjustment and coping for patients and
      families, but also for health professionals. This paper focuses on the question
      of the follow-up of cancer patients and highlights some of the difficulties faced
      by professionals and institutions when attempting to improve the quality of care
      in this field. We describe how the divisions of general medical rehabilitation
      and of oncology of the Geneva university hospitals promote the implementation of
      supportive oncological care practice in a rehabilitation centre.

PMID- 16300286
TI  - [Aphthous ulcerations, an undesirable little-known effect of antihypertensive
      agents].

PMID- 16300287
TI  - [Avian flu, this new menace that hangs over our heaven (7)].

PMID- 16300288
TI  - [Of wine tasting and the placebo effect].

PMID- 16300289
TI  - [Stochastic].

PMID- 16300290
TI  - [Outcome of very low birthweight infants].

PMID- 16300291
TI  - [Complement and age related macular degeneration].

PMID- 16300292
TI  - [Bone density tests for results or just for testing?].

PMID- 16300293
TI  - [Celiac disease].

PMID- 16300294
TI  - [Acquired osteoporosis in childhood].

PMID- 16300295
TI  - [Gaucher disease].

PMID- 16300296
TI  - [Q for query, questions and answers concerning Q-fever].

PMID- 16300297
TI  - [Directions for allogenic stem cell transplants and how they reflect on the
      operation and results of the transfer center in Turku].

PMID- 16300298
TI  - [Mortality among alcoholics, results from 16 year follow up].

PMID- 16300299
TI  - [Painful knee].

PMID- 16300300
TI  - [Psychotic symptoms due to brain tumor].

PMID- 16300302
TI  - [Frequent falls in a patient with a pacemaker].

PMID- 16300301
TI  - [Update on current care guidelines. Proper care of medical problems connected to
      Down Syndrome].

PMID- 16300304
TI  - [Risks and risk factors of blood transfusion].

PMID- 16300303
TI  - [Severe headache of a young woman].

PMID- 16300305
TI  - [How to guarantee the quality of breast cancer surgeries in Finland].

PMID- 16300306
TI  - [Alcohol consumption among young people].

PMID- 16300307
TI  - [Law and ethics concerning artificial fertilization].

PMID- 16300308
TI  - [Care and treatment of insomnia].

PMID- 16300309
TI  - [CT angiography of carotid artery].

PMID- 16300310
TI  - [Cardiogenic brain embolism].

PMID- 16300311
TI  - [The risk of infectious diseases after natural disasters].

PMID- 16300313
TI  - [Changing diagnosis and surgical treatment of breast cancer].

PMID- 16300312
TI  - [The efficacy of treating eating disorders].

PMID- 16300314
TI  - [Emergency care and follow-up of traumatic dental injuries].

PMID- 16300315
TI  - [Tracheal rupture after endotracheal intubation].

PMID- 16300316
TI  - [Symptoms of upper arms when lifted].

PMID- 16300317
TI  - [Zen and maintenance of mitochondria].

PMID- 16300318
TI  - [Response to: "Zen and maintenance of mitochondria"].

PMID- 16300319
TI  - [Obesity among children].

PMID- 16300320
TI  - [Caries prevalence and oral health among schoolchildren].
AB  - Last decennia much attention has been paid to improve the oral health of
      schoolchildren. The purpose of this study was to examine the present caries
      prevalence and the state of oral health of schoolchildren. Therefore 1.147
      children from group 2 and group 8 of the primary school (6 and 12 years of age)
      in the province Drenthe were examined. Of the children 33% had caries and 13% had
      gingivitis. The highest percentages of caries were found in the low SES-group and
      among children that have education at schools for children with special needs.
      The study showed that these children brushed their teeth less often, they visited
      the dentist for the first time at an older age and they were eating many snacks.
      Children who had received an instruction in how to brush one's teeth, did not
      score better in the caries prevalence compared to children without previous
      instruction. Also the children whose parents had information about oral health,
      did not score better than the other children.

PMID- 16300321
TI  - [A survey of implant-retained superstructure types in the edentulous mandible in
      The Netherlands].
AB  - Treatment of mandibular edentulousness with endosseous permucosal implants has
      evolved to a common treatment option during the last decades. In The Netherlands,
      the relative cheap prosthetic treatment of implant-supported overdentures is
      considered a qualitatively adequate treatment. The aim of the study described in
      this article was to survey the treatment of edentulous mandibles by fixed implant
      supported prostheses and implant-supported overdentures, and to register the
      different mesostructures used. All clinics of special dental care and all larger
      clinics for implant dentistry in The Netherlands received a questionnaire. The
      data provided showed that more than 90% of patients treated with implants because
      of mandibular edentulousness, were provided with an overdenture. In 85% of cases
      a bar-clip mesostructure was used. Cost control was the most important reason to
      choose an overdenture above a fixed implant-supported prosthesis.

PMID- 16300322
TI  - [Direct access to the dental hygienist 1. Opinions of relevant national
      organizations].
AB  - The opinions of professional dental organisations, the government (Ministry of
      Health), patient organizations and the medical assurance companies are collected
      on the question whether patients could visit the dental hygienist without being
      seen by a dentist first. The general opinion is that this could be possible for
      those treatments for which the dental hygienist are fully qualified. However, the
      professional organizations of the dentists claim that the dentist should always
      be responsible for the patient register and thereby the first responsible for the
      dental health of the patients. Pilot projects are advised to study how the
      various dental workers can most efficiently work together.

PMID- 16300323
TI  - [The future of dental amalgam].
AB  - This paper is a comment on 'The enigma of dental amalgam' by Carl Leinfelder
      published in 2004 in the Journal of Esthetic and Restorative Dentistry. In that
      paper a warning is stated against a too abrupt change from amalgam towards resin
      composite, because this will bring a lot of clinical problems due to the limited
      skills of todays' dentists in placing posterior composite resin restorations.
      However, the situation in The Netherlands is different since a gradual changeover
      from amalgam towards resin composites has taken place during the last decades and
      dental schools have skipped training in placing amalgam restorations out of the
      curriculum. Clinical studies on the longevity of amalgam and resin composite
      restorations placed by dental students and dentists who are experienced in both
      composite resin and amalgam placement show a comparable and acceptable annual
      failure rate for those restorations. It is concluded that a gradual changeover
      from amalgam towards composite resin is preferred to avoid clinical problems.

PMID- 16300324
TI  - [Search for clinician-researchers].
AB  - One of the goals in dental education is to teach students the principles of
      evidence-based dentistry. This requires the input of scientifically trained
      clinical staff. It is important to explore and find ways that will invite young
      and ambitious clinicians to choose for an academic career in which they combine
      clinical excellence with commitment to science. Various options are discussed
      that might seduce young clinicians to enter academia and help create a climate in
      which the dental student of tomorrow will be educated as a critically thinking
      scientifically trained dentist who is prepared for life-long learning.

PMID- 16300325
TI  - [Dissertations 25 years after the date 7. Temporomandibular joint ankylosis].
AB  - Ankylosis of the temporomandibular joint and the possibly associated deformation
      of maxillofacial bones are functionally and aesthetically serious problems.
      Despite the developments in oral and maxillofacial surgery, treatment of patients
      with ankylosis of the temporomandibular joint still remains challenging. This
      article presents a review of the developments in this treatment, 25 years after
      the publication of the thesis 'Temporomandibular joint ankylosis'. Nowadays,
      computer-tomography is the standard for imaging assessment, possibly combined
      with stereolithography. Resection of the ankylotic mass is the surgery method of
      choice. The gap is filled by interpositional tissue transfer of temporalis muscle
      or a fascia flap. Early mobilisation and intensive physiotherapy are needed. In
      case of maxillofacial asymmetry, distraction osteogenesis has proved to be
      successful.

PMID- 16300326
TI  - [Electives at the dental school in Groningen].
AB  - To offer a more comprehensive curriculum in various dental topics, the dental
      school of the University of Groningen developed electives. This article gives an
      overview of the learning objectives of the different electives, the program and
      the way in which students are examined. Attention is also paid to some
      experiences of students and teachers with this kind of education. The electives
      seem to effectively prepare students for specific parts of dentistry, and they
      give an orientation on the scientific aspects of dentistry. Students and teachers
      are positive about the electives. The electives give good opportunities to the
      assessment of professional behavior.

PMID- 16300327
TI  - [Mopping with open faucets: immune system in sputum].

PMID- 16300328
TI  - [Oral pathology in a denture practice].
AB  - An 86-year-old edentulous patient visits a denturist for the provision of a new
      set of dentures. In the region 36/37 of the lower denture base extension is a
      bony like structure apparent, that does really not bother the patient. The
      denturist refers the patient for further diagnosis. It appeared to be a benign
      condition (traumatic periosteal ossification) that did not require surgical
      intervention. The responsibilities and capabilities of the denturist with regard
      to the treatment of edentulous patients are discussed in light of the current
      Dutch legislation.

PMID- 16300329
TI  - [A swelling in the midline of the mandible caused by a ossifying fibroma].
AB  - A 34-year-old woman complained of a swelling in the midline of the mandible,
      present for about six months and diagnosed as ossifying fibroma. Because of the
      rapid development and the extent of the tumour, treatment consisted of a partial
      mandibulectomy, followed by immediate reconstruction with a free vascularized
      fibula transplant.

PMID- 16300330
TI  - [Obesity and oral health].
AB  - Obesity has a prevalence of approximately 10% among Dutch adults. It is a
      chronic, incurable disease with a high mortality and co-morbidity. The co
      morbidity can be reduced significantly by a sustained moderate weight loss (5
      15%). The main cause of obesity is an imbalance between energy intake and energy
      expenditure. The primary treatment combines dietary education, behaviour
      modification and increased physical activity, followed by pharmacotherapy or
      surgery when necessary. Obesity is related to several aspects of oral health,
      such as caries, periodontitis and xerostomia. In addition, obesity may have
      implications for dental treatment.

PMID- 16300331
TI  - [Structural changes in the portal vein wall in liver cirrhosis. Studies with the
      unfolded venous tube].

PMID- 16300332
TI  - [Comparative morphologic and histochemical studies of intrarenal blood vessels in
      arterio-arteriolarsclerosis of the kidney without diabetes mellitus and in
      diabetic glomerulosclerosis].

PMID- 16300333
TI  - [Immunohistologic findings in 3 cases of human secondary amyloidosis].

PMID- 16300334
TI  - [Fatal massive pulmonary hemorrhage due to bronchial carcinoma].

PMID- 16300335
TI  - [Calcium deposits in the funiculus spermaticus with special reference to diabetes
      mellitus].

PMID- 16300336
TI  - [Thyroid gland findings in stillborn and newborn infants].

PMID- 16300337
TI  - [Ultrastructural and histochemical studies of incipient viomycin nephrosis].

PMID- 16300338
TI  - [Immunohistochemical studies of liver punch biopsies from patients with chronic
      hepatitis].

PMID- 16300339
TI  - [Endangiitis obliterans in infancy].

PMID- 16300340
TI  - Effect of ionizing radiation on the endocrine function of pancreas.

PMID- 16300341
TI  - A study on the cardiovascular and pulmonar action of ketamine in conscious dogs.

PMID- 16300342
TI  - Local fibrinolytic activity of vessel wall and venous pressure.

PMID- 16300343
TI  - Colorimetric determination of total cholesterol in serum/plasma with perchloric
      acid and mercuric nitrate.

PMID- 16300344
TI  - Phagocytosed bacteria in circulating histiocytes a neglected sign in bacterial
      endocarditis.

PMID- 16300345
TI  - Fibrinolytic activity variations before and after normal delivery.

PMID- 16300346
TI  - Further observations of foot and mouth disease virus type S.A.T 1 infection of
      cattle in Tanzania.

PMID- 16300347
TI  - Infectious bursal disease in Ghana.

PMID- 16300348
TI  - A serological survey of the prevalence of brucellosis in pigs in Kenya.

PMID- 16300349
TI  - Bovine brucellosis in the southern regions of the Somali Democratic Republic.

PMID- 16300350
TI  - Salmonellosis in Nigerian livestock.

PMID- 16300351
TI  - Salmonella serotype from slaughter house at Kano abattoir: a short communication.

PMID- 16300352
TI  - Babesiosis in neonatal calves: a case report.

PMID- 16300353
TI  - Serological reactions in possible human toxoplasmosis in parts of East Central
      State of Nigeria.

PMID- 16300354
TI  - The protection of 80 Nigerian trade cattle from trypanosomiasis and liver flukes
      using Samorin 1 and Trodax 2.

PMID- 16300355
TI  - Studies of experimental Trypanosoma evansi infection in goats.

PMID- 16300356
TI  - A check list of helminth parasites of domestic animals in Nigeria.

PMID- 16300357
TI  - Parasitic diseases of animals in the Republic of Zaire.

PMID- 16300358
TI  - Effect of desiccation on survival of the infective larvae of Osteriagia
      ostertagi.

PMID- 16300359
TI  - Bovine cysticercosis in the Republic of Zaire.

PMID- 16300360
TI  - Hfpatovenous occlusion in desert sheep.

PMID- 16300361
TI  - Preliminary observations on the anthelmintic activity of Jatropha curcas against
      strongyloides and Haemonchus infections in goats and sheep.

PMID- 16300362
TI  - Final report of compatibility test involving Trodax and Salmorin.

PMID- 16300363
TI  - Haematological studies in N'dama, German Brown and N'dama x Brown cows.

PMID- 16300365
TI  - Blood work.

PMID- 16300364
TI  - Serum electrolyte and protein values in the N'dama, German Brown and N'dama/Brown
      (crossbred) cows.

PMID- 16300367
TI  - The great Canadian drug novel.

PMID- 16300366
TI  - The Tamiflu tug of war.

PMID- 16300368
TI  - The doctor is out. How GM's deal to cut its medical benefits hurts every retiree.

PMID- 16300369
TI  - What ails health stocks?

PMID- 16300370
TI  - Differences in lysine adduction by acrolein and methyl vinyl ketone: implications
      for cytotoxicity in cultured hepatocytes.
AB  - Acrolein is a highly toxic environmental pollutant that readily alkylates the
      epsilon-amino group of lysine residues in proteins. In model systems, such
      chemistry involves sequential addition of two acrolein molecules to a given
      nitrogen, forming bis-Michael-adducted species that undergo aldol condensation
      and dehydration to form Nepsilon-(3-formyl-3,4-dehydropiperidino)lysine. Whether
      this ability to form cyclic adducts participates in the toxicity of acrolein is
      unknown. To address this issue, we compared the chemistry of protein adduction by
      acrolein to that of its close structural analogue methyl vinyl ketone, expecting
      that the alpha-methyl group would hinder the intramolecular cyclization of any
      bis-adducted species formed by methyl vinyl ketone. Both acrolein and methyl
      vinyl ketone displayed comparable protein carbonylating activity during in vitro
      studies with the model protein bovine serum albumin, confirming the alpha,beta,
      unsaturated bond of both compounds is an efficient Michael acceptor for protein
      nucleophiles. However, differences in adduction chemistry became apparent during
      the use of electrospray ionization-MS to monitor reaction products in a lysine
      containing peptide after modification by each compound. For example, although a
      Schiff base adduct was detected following reaction of the peptide with acrolein,
      an analogous species was not formed by methyl vinyl ketone. Furthermore, while
      ions corresponding to mono- and bis-Michael adducts were detected at the N
      terminus and lysine residues following peptide modification by both carbonyls,
      only acrolein modification generated ions attributable to cyclic adducts. Despite
      these differences in adduction chemistry, in mouse hepatocytes, the two compounds
      exhibited very comparable abilities to induce rapid, concentration-dependent cell
      death as well as protein carbonylation. These findings suggest that the acute
      toxicity of short-chain alpha,beta-unsaturated carbonyl compounds involves their
      ability to form acyclic Michael addition adducts rather than Schiff conjugates or
      heterocyclic adducts.

PMID- 16300371
TI  - Effects of 3-methylcholanthrene on gene expression profiling in the rat using
      cDNA microarray analyses.
AB  - There is significant human exposure to polycyclic aromatic hydrocarbons (PAHs),
      many of which are bioactivated by the cytochrome P450 (P450) 1A family of enzymes
      to metabolites that are capable of covalently binding to DNA, a critical step in
      the initiation of carcinogenesis. We reported earlier that exposure of rats to 3
      methylcholanthrene (MC) causes sustained induction of hepatic cytochrome P4501A
      expression for up to 45 days. Here, we tested the hypothesis that MC elicits
      persistent induction of other genes that are regulated by the Ah receptor (AHR).
      Female Sprague-Dawley rats were treated with MC (100 micromol/kg) ip once daily
      for 4 days, and gene expression patterns were investigated using total liver RNA
      isolated from animals at 1, 15, and 28 days after MC withdrawal. Gene expression
      was studied by cDNA microarray analyses using 4608 unique clones from liver
      derived expressed sequence tag (EST) libraries fortified with clones of known
      liver genes representing approximately 4000 genes. Several phase I (P4501A1, 
      1A2) and phase II [e.g., glutathione-S-transferase (GST)-M1, UDP-glucuronosyl
      transferases (UGT)] genes were persistently induced (3-10-fold) by MC for 15-28
      days. The persistent induction of P4501A1 gene expression was confirmed by real
      time reverse transcriptase polymerase chain reaction (RT-PCR) experiments. MC
      also elicited a 5-fold persistent augmentation of acute phase genes such as
      orosomucoid 1 and alpha-1-acid glycoprotein (AGP), and this was accompanied by
      sustained liver damage and inflammation in the MC-exposed rats. In conclusion,
      our results strongly suggest that sustained induction of P4501A1 by MC is
      accompanied by persistent expression of other genes belonging to the Ah gene
      battery, as well as certain other genes involved in toxic responses. Elucidating
      the mechanisms of persistent induction of P4501A1 and other genes by MC might
      lead to a better understanding of the mechanisms of toxicity mediated by PAHs.

PMID- 16300372
TI  - Alterations in gene expression induced by the lipid peroxidation product, 4
      hydroxy-2-nonenal.
AB  - Reactive intermediates produced during oxidative stress are believed to
      contribute to the development and progression of a variety of age-related
      diseases. 4-hydroxy-2-nonenal (HNE), an abundant product of polyunsaturated fatty
      acid oxidation and decomposition, reacts extensively with DNA and proteins,
      depletes intracellular glutathione, and alters many cell signaling cascades,
      including those regulating apoptosis. Using microarray technology, global changes
      in gene expression were monitored temporally at subcytotoxic and cytotoxic HNE
      doses in RKO human colorectal carcinoma cells, with the highest level of changes
      being observed at cytotoxic doses. Gene expression alterations were confirmed
      using real-time reverse transcription polymerase chain reaction, Western
      blotting, and transcription factor reporter profiling. Significant alterations
      were observed in genes regulated by the antioxidant, heat shock, ER stress, and
      nutrient deprivation responses. Our results demonstrate that HNE simultaneously
      affects multiple stress signaling pathways, many of which represent potential
      mechanisms through which HNE alters cellular viability and response to damage.

PMID- 16300373
TI  - Genomic analysis of murine pulmonary tissue following carbonyl chloride
      inhalation.
AB  - Carbonyl chloride (phosgene) is a toxic industrial compound widely used in
      industry for the production of synthetic products, such as polyfoam rubber,
      plastics, and dyes. Exposure to phosgene results in a latent (1-24 h),
      potentially life-threatening pulmonary edema and irreversible acute lung injury.
      A genomic approach was utilized to investigate the molecular mechanism of
      phosgene-induced lung injury. CD-1 male mice were exposed whole body to either
      air or a concentration x time amount of 32 mg/m3 (8 ppm) phosgene for 20 min (640
      mg x min/m3). Lung tissue was collected from air- or phosgene-exposed mice at
      0.5, 1, 4, 8, 12, 24, 48, and 72 h postexposure. RNA was extracted from the lung
      and used as starting material for the probing of oligonucleotide microarrays to
      determine changes in gene expression following phosgene exposure. The data were
      analyzed using principal component analysis to determine the greatest sources of
      data variability. A three-way analysis of variance based on exposure, time, and
      sample was performed to identify the genes most significantly changed as a result
      of phosgene exposure. These genes were rank ordered by p values and categorized
      based on molecular function and biological process. Some of the most significant
      changes in gene expression reflect changes in glutathione synthesis and redox
      regulation of the cell, including upregulation of glutathione S-transferase alpha
      2, glutathione peroxidase 2, and glutamate-cysteine ligase, catalytic subunit
      (also known as gamma-glutamyl cysteine synthetase). This is in agreement with
      previous observations describing changes in redox enzyme activity after phosgene
      exposure. We are also investigating other pathways that are responsive to
      phosgene exposure to identify mechanisms of toxicity and potential therapeutic
      targets.

PMID- 16300375
TI  - The role of aromatic amino acid oxidation, protein unfolding, and aggregation in
      the hypobromous acid-induced inactivation of trypsin inhibitor and lysozyme.
AB  - Hypobromous acid (HOBr) generated by activated eosinophils has been implicated in
      tissue injury observed in asthma, allergic reactions, and some infections.
      Proteins are major targets for this oxidant, but the mechanisms by which HOBr
      induces loss of function are not well-established. In this study, we have
      examined the effect of HOBr on protein structure (as assessed by amino acid loss,
      side chain oxidation, fragmentation, aggregation, and unfolding) and activity of
      a model protease inhibitor, soybean trypsin inhibitor (STI), and the protective
      enzyme lysozyme. Exposure of both proteins to low oxidant concentrations (< or =
      5-fold molar excess) results in loss of function. In each case, loss of activity
      is associated with the selective oxidation of His, Trp, and Tyr residues, which
      results in protein unfolding (with lysozyme) and protein aggregation (with STI).
      Reaction with these residues accounts for 25 and 50% of the HOBr with STI (25
      fold excess) and lysozyme (4-fold excess), respectively. These processes are
      believed to lead to changes in the structure of the proteins, which disrupts
      substrate binding. With both proteins, the oxidation of other residues, including
      Met, does not appear to play a major role. Bromamines, formed by reaction with
      amine groups, are major products, which account for 45 and 35% of the HOBr with
      STI (25-fold excess) and lysozyme (4-fold excess), respectively. Decomposition of
      these species correlates with secondary oxidation reactions, and with lysozyme, a
      time-dependent loss in activity. Overall, 70% of the HOBr can be accounted for
      with STI and 95% with lysozyme.

PMID- 16300374
TI  - Effects of beauvericin on the metabolic state and ionic homeostasis of
      ventricular myocytes of the guinea pig.
AB  - Beauvericin, a cyclic hexadepsipeptide with antibiotic properties, has been shown
      to reduce contraction force and to affect action potential parameters of guinea
      pig papillary muscles. Its potential to form cation-selective channels in
      mammalian membranes has been demonstrated. Patch clamp and fluorescence imaging
      techniques were used to investigate its effects in enzymatically isolated
      ventricular myocytes. Application of 10 microM beauvericin caused a large [Ca2+]i
      increase in Fura 2AM-loaded cardiomyocytes leading to cell shortening. The effect
      could be partially inhibited by ryanodine pretreatment and was largely dependent
      on external Ca2+ and blocked by 5 mM Ni2+. Beauvericin initiated a progressive
      increase in [Mg2+]i, the time course of which developed similarly upon increasing
      the external chemical gradient of Mg2+ 10-fold, to produce an ionophoric
      challenge. Monitoring of pH(i) with BCECF showed that beauvericin caused
      cytosolic acidification. Confocal microscopy revealed mitochondrial
      depolarization in TMRM-loaded cardiomyocytes, which resembled the effect of
      classical mitochondrial uncouplers. However, the NADH autofluorescence signal
      followed a biphasic pattern, in contrast to the NADH response to the uncouplers
      FCCP and the K+-ionophore valinomycin. These results suggest that beauvericin,
      possibly via its ionophoric properties, acts as an atypical mitochondrial
      uncoupler, greatly disturbs the physiological ionic balance and pH, challenges
      cellular metabolism, and causes ATP depletion.

PMID- 16300376
TI  - D-amino-acid oxidase is involved in D-serine-induced nephrotoxicity.
AB  - D-serine is nephrotoxic in rats. Based on circumstantial evidence, it has been
      suspected that D-amino-acid oxidase is involved in this nephrotoxicity. Since we
      found that LEA/SENDAI rats lacked D-amino-acid oxidase, we examined whether this
      enzyme was associated with D-serine-induced nephrotoxicity using the LEA/SENDAI
      rats and control F344 rats. When d-propargylglycine, which is known to have a
      nephrotoxic effect through its metabolism by D-amino-acid oxidase, was injected
      intraperitoneally into the F344 rats, it caused glucosuria and polyuria. However,
      injection of d-propargylglycine into LEA/SENDAI rats did not cause any glucosuria
      or polyuria, indicating that D-amino-acid oxidase is definitely not functional in
      these rats. D-serine was then injected into the F344 and LEA/SENDAI rats. It
      caused glucosuria and polyuria in the F344 rats but not in the LEA/SENDAI rats.
      These results indicate clearly that D-amino-acid oxidase is responsible for the D
      serine-induced nephrotoxicity.

PMID- 16300377
TI  - Formation of inter- and intrastrand imine type DNA-DNA cross-links through
      secondary reactions of aldehydic adducts.
AB  - Acrolein-derived DNA adducts of guanine have previously been detected in tissues
      of several species, including humans, and have been shown to be mutagenic in
      mammalian cells and potentially carcinogenic in higher organisms. In duplex DNA,
      the predominant acrolein-derived lesion, gamma-hydroxy-1,N2-propanodeoxyguanosine
      (gamma-HOPdG), exists in an equilibrated mixture of ring-opened and ring-closed
      forms. We have previously shown that the acyclic form can undergo secondary
      chemical reactions to form both interstrand DNA-DNA cross-links in a CpG sequence
      context and DNA-protein and DNA-peptide cross-links. Investigations using duplex
      DNAs containing gamma-HOPdG in a CpG sequence context reversibly created at least
      two cross-linked species: an imine, which is a minor species but could be readily
      reduced by NaBH4, and a major heat labile, nonreducible species that we formulate
      as a carbinolamine cross-link. The DNA came to equilibrium over several days with
      the carbinolamine species being significantly more abundant than the reducible
      imine. In an effort to find other types of DNA-DNA cross-links, we have developed
      a high throughput screen to evaluate the effects of DNA sequence and lesion
      structure on the formation of reducible interstrand and intrastrand cross-links.
      These data reveal that four different lesions, two involving deoxyguanosine and
      two involving deoxyadenosine, can react with nearby bases to form inter- and
      intrastrand DNA cross-links.

PMID- 16300378
TI  - Bioactivation of dibrominated biphenyls by cytochrome P450 activity to
      metabolites with estrogenic activity and estrogen sulfotransferase inhibition
      capacity.
AB  - Exposure of humans and wildlife to xenobiotics, such as halogenated biphenyls,
      that interfere with the endogenous estrogen balance may lead to endocrine
      disruption. Such compounds may either mimic or block estradiol's action by
      agonistic or antagonistic action, respectively. They may also affect endogenous
      estradiol concentrations by induction or inhibition of enzymes that metabolize
      estradiol. In the present study, we demonstrate that estrogenic metabolites of
      two brominated biphenyls, 2,2'-dibromobiphenyl (2,2'-DBB) and 4,4'
      dibromobiphenyl (4,4'-DBB), are formed by rat liver microsomal cytochrome P450
      (CYP) activity. Bioactivation of 2,2'-DBB and 4,4'-DBB yielded various mono- and
      dihydroxylated bromobiphenyl metabolites, which were collected by preparative
      HPLC and analyzed by LC/MS. Several of the metabolites bound to the estrogen
      receptor (ER) activated the ER and inhibited human estrogen sulfotransferase
      (hEST). Seven monohydroxylated metabolites were positively identified using
      synthetic monohydroxylated reference compounds. These synthetic monohydroxylated
      bromobiphenyls also bound to and activated the ER and inhibited hEST. The highest
      ER affinity was observed for 4-OH-2,2'-DBB, with an EC50 of 6.6 nM. The highest
      ER activation was observed for 4-OH-3,4'-DBB (EC50 of 74 nM) while 4-OH-4'-MBB
      and 4-OH-2,2'-DBB induced a supramaximal (as compared to estradiol) ER
      activation. The strongest hEST inhibition was found with 4-OH-3,4'-DBB (EC50 = 40
      nM). In conclusion, we show that two dibrominated biphenyls are bioactivated by
      CYP activity into very potent estrogenic metabolites and inhibitors of hEST.
      These findings are of vital importance for accurate risk assessment of exposure
      to environmental contaminants, such as halogenated biphenyls. Neglecting
      bioactivation through biotransformation will lead to underestimation of health
      risks of this class of xenobiotics.

PMID- 16300380
TI  - Formation of DNA adducts with cholyl adenylate, a putative intermediate for
      biosynthesis of cholyl-CoA.
AB  - Cholyl adenylate is a putative intermediate for biosynthesis of cholic acid
      coenzyme A (CoA) thioester conjugates by acyl-CoA synthetase. Early studies
      showed the conjugated acid anhydride moiety of cholyl adenylate to be reactive,
      attacking proteins to form protein-cholic acid adducts. In the present study, to
      clarify reactions of cholyl adenylate with DNA under physiological conditions,
      products with nucleosides were analyzed. HPLC-MS analyses indicated cholyl
      adenylate to primarily attack hydroxy groups of ribose moieties of nucleosides.
      Moreover, as speculated from UV and MS studies, exocyclic amino groups of 2'
      deoxycytidine and 2'-deoxyadenosine were found to serve as targets of cholyl
      adenylate; the corresponding cholic amides, N4-cholyl-2'-deoxycytidine and N6
      cholyl-2'-deoxyadenosine, were formed at yields of 0.32 and 0.06%, respectively.
      Structures of these base modified adducts were confirmed by direct comparison
      with synthetic compounds obtained from coupling reactions of cholic acid with
      each nucleoside in the presence of dicyclohexylcarbodiimide in pyridine at 70
      degrees C. N4-Cholyl-2'-deoxycytidine was also obtained at a level of 1.6 adducts
      per 10(5) nucleosides from enzymatic hydrolysates of calf thymus DNA reacted with
      cholyl adenylate. These results suggest that cholyl adenylate, released from CoA
      synthetase, may have some possibility as a DNA modifier in vivo.

PMID- 16300381
TI  - Synthesis and stability studies of the glutathione and N-acetylcysteine adducts
      of an iminoquinone reactive intermediate generated in the biotransformation of 3
      (N-phenylamino)propane-1,2-diol: implications for toxic oil syndrome.
AB  - Epidemiological studies have pointed to fatty acid mono- and diesters of 3-(N
      phenylamino)propane-1,2-diol (PAP) as the biomarkers of the toxic oil batches
      that caused toxic oil syndrome (TOS), an intoxication episode that occurred in
      Spain in 1981, causing over 400 deaths and affecting more than 20000 people. The
      biotransformation of PAP administered intraperitoneally to two mouse strains
      produced potentially toxic metabolites. The identification of 3-(4'
      hydroxyphenylamino)propane-1,2-diol among those metabolites was important because
      the compound can generate the quinoneimine intermediate 2. The potential toxicity
      of quinoneimines has been attributed primarily to their electrophilic character.
      Accordingly, the reactions of 2 with N-acetylcysteine, N-acetylcysteine methyl
      ester, and GSH were investigated. Quinoneimine 2 reacts with the N-acetylcysteine
      methyl ester to give the expected conjugate as a major product, accompanied by
      the corresponding bis and tris adducts. The monoadduct, when isolated in pure
      form, undergoes spontaneous oxidation to generate a new quinoneimine
      intermediate, which in turn rearranges and undergoes hydrolysis to afford the
      thiol adduct formally derived from the quinoneimine generated from p-aminophenol.
      The same overall pathway was observed for the reaction of 2 with N-acetylcysteine
      and GSH. Both thiol reagents reacted with the quinoneimine to give the
      corresponding adducts in which the addition took place at the ortho position with
      respect to the amino group. These conjugates were also unstable and ultimately
      afforded the corresponding adduct derived from p-aminophenol. The relevancy of
      these results to TOS, as well as their potential generalization for quinoneimines
      derived from other xenobiotics, is discussed herein.

PMID- 16300382
TI  - In vitro and in vivo studies on acyl-coenzyme A-dependent bioactivation of
      zomepirac in rats.
AB  - Zomepirac [ZP, 5-(chlorobenzoyl)-1,4-dimethylpyrrole-2-acetic acid] was withdrawn
      from the market because of unpredictable allergic reactions that may have been
      caused by ZP-protein adducts formed by reaction of the reactive acyl glucuronide
      of ZP (ZP-O-G) with endogenous proteins. To test the hypothesis that the reactive
      ZP acyl coenzyme A thioester (ZP-CoA) was formed and potentially could contribute
      to formation of ZP-protein adducts, we investigated the acyl CoA-dependent
      metabolism of ZP in freshly isolated rat hepatocytes (1 mM) and in vivo (100 mg
      ZP/kg, ip) in rat livers (2 h after dose administration), rat bile (0-4 h), and
      rat urine (0-24 h). ZP-CoA was detected in freshly isolated hepatocytes and in
      vivo in rat livers by LC/MS/MS. In addition, the ZP glycine conjugate (ZP-Gly)
      and ZP taurine conjugates (ZP-Tau) were identified by LC/MS/MS in rat hepatocytes
      and in vivo in rat livers, rat urine, and rat bile. The identities of ZP-CoA, ZP
      Gly, and ZP-Tau were confirmed by comparison of retention times and MS/MS spectra
      with those of authentic standards. Moreover, the ZP acyl carnitine ester was
      detected in rat urine and rat bile based upon (i) the chlorine isotope pattern,
      (ii) MS/MS spectra showing significant ions characteristic for carnitine (m/z 60,
      144 and loss of m/z 59) and ZP (m/z 139), and (iii) accurate mass measurements
      with a mass accuracy of 0.2 ppm. ZP-CoA serves as an obligatory intermediate in
      the formation of ZP-Gly, ZP-Tau, and ZP carnitine ester, and it is therefore of
      mechanistic significance that these conjugates were identified. Finally, time
      dependent concentration profiles obtained in experiments with rat hepatocytes and
      in vivo from quantitative analysis of rat livers indicate that ZP-CoA, in
      addition to ZP-O-G, may contribute to formation of the potentially toxic covalent
      ZP-protein adducts.

PMID- 16300383
TI  - Base selectivity and effects of sequence and DNA secondary structure on the
      formation of covalent adducts derived from the equine estrogen metabolite 4
      hydroxyequilenin.
AB  - Equilenin, an important component of a widely prescribed hormone replacement
      formulation for postmenopausal women, is metabolized by mammalian P450 enzymes to
      the catechol 4-hydroxyequilenin (4-OHEN). The oxidized o-quinone derivative of 4
      OHEN is known to form cyclic covalent adducts with DNA [Bolton, J. (1998) Chem.
      Res. Toxicol. 11, 1113] in vitro and in vivo. The characteristics of 4-OHEN-DNA
      adduct formation were investigated with the oligonucleotides 5'-d(CCATCGCTACC)
      (I), its complementary strand 5'-d(GGTAGCGATGG) (II), one rich in C and the other
      in G, and the duplexes I.II. The identities of the modified bases were elucidated
      in terms of four stereoisomeric 4-OHEN-2'-deoxynucleoside standards described
      earlier [Shen et al. (2001) Chem. Res. Toxicol. 11, 94; Embrechts et al. J. Mass
      Spectrom. 36, 317). The reactions of 4-OHEN with C are favored overwhelmingly in
      both single-stranded I and II with no guanine adducts observed in either case,
      and only minor proportions of A adducts were detected in sequence II. However,
      guanine adducts are observed in oligonucleotides that contain only G and
      unreactive T residues. The relative levels of cyclic covalent adducts observed in
      single-stranded I, II, and duplex I.II are approximately 54:21:5, with only the
      end C groups in I modified in the I.II duplex. When 4-OHEN is reacted with calf
      thymus DNA, the reaction yield of cyclic adducts is more than approximately 10(3)
      fold lower than in I. The cyclic 4-OHEN adducts lead to a pronounced thermal
      destabilization of duplexes I.II. Overall, cyclic adduct formation is markedly
      dependent on the sequence context and secondary structure of the DNA. The latter
      effect is attributed to the poor accessibilities of 4-OHEN to the reactive
      nucleotide Watson-Crick hydrogen-bonding interface in the interior of the duplex.
      In the single-stranded oligonucleotides I and II, the strikingly different
      selectivities of adduct formation are attributed to the formation of noncovalent
      preassociation complexes that favor reaction geometries with C, rather than with
      A or G. Finally, the levels of several typical biomarkers of oxidative DNA damage
      (including 8-oxo-2'-deoxyguanosine) are formed in I in aqueous solutions with a
      yield at least 10 times smaller than the yield of cyclic 4-OHEN-dC adducts under
      identical reaction conditions.

PMID- 16300379
TI  - Site specific synthesis and polymerase bypass of oligonucleotides containing a 6
      hydroxy-3,5,6,7-tetrahydro-9H-imidazo[1,2-a]purin-9-one base, an intermediate in
      the formation of 1,N2-etheno-2'-deoxyguanosine.
AB  - The reaction of DNA with certain bis-electrophiles such as chlorooxirane and
      chloroacetaldehyde produces etheno adducts. These lesions are highly miscoding,
      and some of the chemical agents that produce them have been shown to be
      carcinogenic in laboratory animals and in humans. An intermediate in the
      formation of 1,N2-ethenoguanine is 6-hydroxy-3,5,6,7-tetrahydro-9H-imidazo[1,2
      a]purin-9-one (6-hydroxyethanoguanine), which undergoes conversion to the etheno
      adduct. The chemical properties and miscoding potential of the hydroxyethano
      adduct have not been previously studied. A synthesis of the hydroxyethano
      adducted nucleoside was developed, and it was site specifically incorporated into
      oligonucleotides. This adduct had a half-life of between 24 and 48 h at neutral
      pH and 25 degrees C at the nucleoside and oligonucleotide levels. The miscoding
      potential of the hydroxyethano adduct was examined by primer extension reactions
      with the DNA polymerases Dpo4 and pol T7-, and the results were compared to the
      corresponding etheno-adducted oligonucleotide. Dpo4 preferentially incorporated
      dATP opposite the hydroxyethano adduct and dGTP opposite the etheno adduct; pol
      T7- preferentially incorporated dATP opposite the etheno adduct while dGTP and
      dATP were incorporated opposite the hydroxyethano adduct with nearly equal
      catalytic efficiencies. Collectively, these results indicate that the
      hydroxyethano adduct has a sufficient lifetime and miscoding properties to
      contribute to the mutagenic spectrum of chlorooxirane and related genotoxic
      species.

PMID- 16300384
TI  - Use of isotopic signatures for mass spectral detection of protein adduction by
      chemically reactive metabolites of bromobenzene: studies with model proteins.
AB  - The cytotoxicity of many small organic compounds often apparently derives from
      their metabolic activation and covalent binding to cellular proteins. It is
      therefore of considerable interest to be able to determine, for a given protoxin,
      which metabolites modify which proteins at which sites. Our laboratory has
      identified more than 45 target proteins for bromobenzene metabolites in liver by
      peptide mass mapping after two-dimensional electrophoresis. Through all of this
      work, we have never observed a bromine-containing peptide. We therefore generated
      model adducted proteins by carbodiimide coupling of Nalpha-acetyl-Ntau-(p
      bromophenyl)-L-histidine (1) and Nalpha-acetyl-Nepsilon-(p-bromophenyl)-L-lysine
      (2) to bovine pancreatic ribonuclease A. For the adducts, RNase-(1)n and RNase
      (2)n, mass spectrometry indicated that n = 0-2 and 0-6, respectively. RNase-(2)n
      was submitted to in-gel and in-solution digestion with trypsin, and the digests
      were analyzed by matrix-assisted laser desorption ionization time-of-flight
      (MALDI-TOF) and liquid chromatgraphy electrospray ionization MS (LC/ESI-MS) and
      tandem MS (MS/MS). Sequence coverages observed ranged from 67% with only three
      modified lysines observed using in-gel digestion and MALDI-TOF analysis, to 100%
      coverage with all 10 lysines observed in both modified and unmodified form using
      in-solution digestion and LC/ESI-MS. In the mass spectra of all modified peptides
      up to 2000 Da, the bromine isotope pattern was obvious by visual inspection; for
      peptides up to 3600 Da, the isotopic signature could be recognized by visual
      comparison to simulated spectra. The presence of Br-containing adducts was
      confirmed by MS/MS analysis of selected peptides. The selection of peaks for
      MS/MS analysis was significantly facilitated by visual recognition of the bromine
      isotope pattern, even at signal-to-noise ratios of 10 (or lower in favorable
      cases). These results indicate that stable isotope labeling may have considerable
      potential for detecting and locating protein adducts of reactive metabolites.

PMID- 16300385
TI  - Characterization of adducts formed in the reaction of 2-chloro-4
      methylthiobutanoic acid with 2'-deoxyguanosine.
AB  - 2-chloro-4-methylthiobutanoic acid (CMBA) is a direct-acting mutagen found in
      salt-nitrite-treated Sanma fish or similarly treated methionine solution. In this
      study, CMBA was reacted with 2'-deoxyguanosine (dG) in phosphate buffer (pH 7.4)
      at 37 degrees C. The HPLC-UV analysis showed that two products were mainly formed
      during the reaction. These were isolated, purified by semipreparative HPLC, and
      characterized as N7-guanine adducts: N7-(3-carboxy-3-methylthiopropyl)guanine
      (A1) and N7-(1-carboxy-3-methylthiopropyl)guanine (A2). Furthermore, liquid
      chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS)
      analysis was employed to investigate the possible formation of minor products
      during the time-course of the reaction of CMBA with dG. It was found that N7-dG
      adducts, the precursors of A1 and A2, were formed early in the reaction and that
      subsequently the spontaneous depurination occurred to yield stable N7-guanine
      adducts A1 and A2. Stability studies in phosphate buffer (pH 7.4) at 37 degrees C
      showed that the amount of each N7-dG adduct decreased rapidly with a half-life of
      6 h and 4 h to yield A1/A2, respectively. A regioisomer of N7-dG adducts was also
      observed in the LC/ESI-MS/MS analysis, but it was not characterized in detail
      because it was present only in trace amounts. On the basis of structural
      features, A1 and A2 seemed to be formed from the reaction of dG with 1-methyl-2
      thietaniumcarboxylic acid, an intermediate resulting from the cyclization of
      CMBA. However, A2 might also have formed from the direct reaction of dG and CMBA.
      N7-Alkylation of the guanine residue and subsequent depurination are known to
      produce apurinic sites in DNA that induce point mutations and may be responsible
      for the observed CMBA-induced mutagenesis.

PMID- 16300387
TI  - Characterization of a deoxyguanosine adduct of tetrachlorobenzoquinone:
      dichlorobenzoquinone-1,N2-etheno-2'-deoxyguanosine.
AB  - Pentachlorophenol (PCP), a widespread environmental pollutant that is possibly
      carcinogenic to humans, is metabolically oxidized to tetrachloroquinone. DNA
      adducts attributable to tetrachloroquinone have been observed previously in vitro
      and detected in vivo. In addition, an unidentified adduct in these studies
      coeluted with the product of the reaction of deoxyguanosine (dG) and
      tetrachlorobenzoquinone (Cl4BQ). We have synthesized, isolated, purified, and
      characterized the predominant adduct formed from the reaction of dG and Cl4BQ.
      The preparation of a 13C-labeled version of this adduct facilitated its
      structural characterization. On the basis of 1H NMR, 13C NMR, MS, IR, UV, and
      cyclic voltammetry, we propose that the adduct is a dichlorobenzoquinone
      nucleoside in which two chlorine atoms in Cl4BQ have been displaced by reaction
      at the 1- and N2-positions of dG. The 1H and 13C NMR chemical shifts are
      consistent with the dichlorobenzoquinone assignment. In contrast, under standard
      analytical conditions, LC-MS data are consistent with a reduced hydroquinone
      structure, similar to what may be expected based on results from other
      chloroquinones. Data from the present study indicate that this reduction could be
      occurring in the electrospray ionization source and that the initial product of
      the reaction of dG and Cl4BQ is a dichlorobenzoquinone. The results of this study
      contribute to the hypothesis that direct reactions between chlorophenols and DNA
      may play a role in the toxic effects of chlorophenols and indicate a potential
      difference in reactivity and biological influence between PCP and other less
      substituted chlorophenols or phenols.

PMID- 16300386
TI  - Synthesis and structure identification of thiol conjugates of (-)
      epigallocatechin gallate and their urinary levels in mice.
AB  - (-)-Epigallocatechin gallate (EGCG), the most abundant and most biologically
      active compound in tea, has been proposed to have many beneficial health effects.
      The metabolic fate of EGCG, however, is not well understood. In the present
      study, we found that EGCG can be oxidized by peroxidase and hydrogen peroxide and
      then reacted with cysteine or glutathione to form conjugates. The structures of
      the cysteine and glutathione conjugates of EGCG were identified using 2D NMR and
      MS. Two thiol conjugates of EGCG (2'-cysteinyl EGCG and 2' '-cysteinyl EGCG) were
      identified by ESI-LC-MS/MS analysis from the urine samples of mice administered
      200 or 400 mg/kg EGCG, i.p. These conjugates were not found in urine samples of
      mice after receiving EGCG at 50 mg/kg i.p., or 2000 mg/kg i.g., or in human urine
      following consumption of 3 g of decaffeinated green tea solids (containing 333 mg
      EGCG). At high doses, EGCG is believed to be oxidized to form EGCG quinone, which
      can react with glutathione to form the thiol conjugates. These results suggest
      that detectable amounts of thiol conjugates of EGCG are formed only after rather
      high doses of EGCG are given to the mice.

PMID- 16300389
TI  - Guanine nucleotide exchange factors operate by a simple allosteric competitive
      mechanism.
AB  - Guanine nucleotide exchange factors are essential components of the mode of
      action of GTPases involved in signal transduction. Their fundamental mechanism is
      generally accepted to derive from stabilization of the nucleotide-free form of
      GTPases, which is reflected in an increase in the rate of GDP dissociation when
      such an exchange factor is bound to a GTPase. The known kinetic properties of
      exchange factors can be explained on the basis of this simple allosteric
      competitive mechanism. Here, we describe experiments designed to distinguish this
      mechanism from a newer model, which invokes an active role for the incoming
      (i.e., displacing) nucleotide, implying the transient formation of a quaternary
      complex consisting of an exchange factor, a GTPase, and two nucleotides, one
      which is being displaced while the other stimulates this displacement. We show
      that for a well-known system (the small GTPase Ras and its exchange factor Cdc25)
      there is no evidence for an effect of the concentration or the nature (i.e., GDP
      or GTP) of the displacing nucleotide on the rate constant of GDP release from the
      Cdc25.Ras.GDP complex, consistent with the simple allosteric competitive model,
      and in disagreement with the newer suggestion. In addition, we present arguments,
      which demonstrate how the erroneous conclusions leading to the alternative model
      were derived.

PMID- 16300390
TI  - Side-chain interactions in the folding pathway of a Fyn SH3 domain mutant studied
      by relaxation dispersion NMR spectroscopy.
AB  - A major challenge to the study of protein folding is the fact that intermediate
      states along the reaction pathway are generally unstable and thus difficult to
      observe. Recently developed NMR relaxation dispersion experiments present an
      avenue to accessing such states, providing kinetic, thermodynamic, and structural
      information for intermediates with small (greater than or equal to approximately
      1%) populations at equilibrium. We have employed these techniques to study the
      three-state folding reaction of the G48M Fyn SH3 domain. Using (13)C-, (1)H-, and
      (15)N-based methods, we have characterized backbone and side-chain interactions
      in the folded, unfolded, intermediate, and transition states, thereby mapping the
      energy landscape of the protein. We find that the intermediate, populated to
      approximately 1%, contains nativelike structure in a central beta-sheet, and is
      disordered at the amino and carboxy termini. The intermediate is stabilized by
      side-chain van der Waals contacts, yet (13)C chemical shifts indicate that methyl
      containing residues remain disordered. This state has a partially structured
      backbone and a collapsed yet mobile hydrophobic core and thus closely resembles a
      molten globule. Nonpolar side-chain contacts are formed in the unfolded
      intermediate transition state; these interactions are disrupted in the
      intermediate-folded transition state, possibly allowing side chains to rearrange
      as they adopt the native packing configuration. This work illustrates the power
      of novel relaxation dispersion experiments in characterizing excited states that
      are "invisible" in even the most sensitive of NMR experiments.

PMID- 16300391
TI  - Two conserved threonines collaborate in the Escherichia coli leucyl-tRNA
      synthetase amino acid editing mechanism.
AB  - The aminoacyl-tRNA synthetases covalently link transfer RNAs to their cognate
      amino acids. Some of the tRNA synthetases have employed an editing mechanism to
      ensure fidelity in this first step of protein synthesis. The amino acid editing
      active site for Escherichia coli leucyl-tRNA synthetase resides within the CP1
      domain that folds discretely from the main body of the enzyme. A portion of the
      editing active site is lined with conserved threonines. Previously, we identified
      one of these threonine residues (Thr(252)) as a critical amino acid specificity
      factor. On the basis of X-ray crystal structure information, two other nearby
      threonine residues (Thr(247) and Thr(248)) were hypothesized to interact with the
      editing substrate near its cleavage site. Single mutations of either of these
      conserved threonine residues had minimal effects on amino acid editing. However,
      double mutations that deleted the hydroxyl group from the neighboring threonine
      residues abolished amino acid editing activity. We propose that these threonine
      residues, which are also conserved in the homologous isoleucyl-tRNA synthetase
      and valyl-tRNA synthetase editing active sites, play a central role in amino acid
      editing. It is possible that they collaborate in stabilizing the transition
      state.

PMID- 16300392
TI  - Structure of the sodium borohydride-reduced N-(cyclopropyl)glycine adduct of the
      flavoenzyme monomeric sarcosine oxidase.
AB  - Monomeric sarcosine oxidase (MSOX) is a flavoprotein that contains covalently
      bound FAD [8a-(S-cysteinyl)FAD] and catalyzes the oxidation of sarcosine (N
      methylglycine) and other secondary amino acids, such as l-proline. Our previous
      studies showed that N-(cyclopropyl)glycine (CPG) acts as a mechanism-based
      inactivator of MSOX [Zhao, G., et al. (2000) Biochemistry 39, 14341-14347]. The
      reaction results in the formation of a modified reduced flavin that can be
      further reduced and stabilized by treatment with sodium borohydride. The
      borohydride-reduced CPG-modified enzyme exhibits a mass increase of 63 +/- 2 Da
      as compared with native MSOX. The crystal structure of the modified enzyme,
      solved at 1.85 A resolution, shows that FAD is the only site of modification. The
      modified FAD contains a fused five-membered ring, linking the C(4a) and N(5)
      atoms of the flavin ring, with an additional oxygen atom bound to the carbon atom
      attached to N(5) and a tetrahedral carbon atom at flavin C(4) with a hydroxyl
      group attached to C(4). On the basis of the crystal structure of the borohydride
      stabilized adduct, we conclude that the labile CPG-modified flavin is a 4a,5
      dihydroflavin derivative with a substituent derived from the cleavage of the
      cyclopropyl ring in CPG. The results are consistent with CPG-mediated
      inactivation in a reaction initiated by single electron transfer from the amine
      function in CPG to FAD in MSOX, followed by collapse of the radical pair to yield
      a covalently modified 4a,5-dihydroflavin.

PMID- 16300393
TI  - Composition of pH-sensitive triad in C-lobe of human serum transferrin.
      Comparison to sequences of ovotransferrin and lactoferrin provides insight into
      functional differences in iron release.
AB  - The transferrins (TF) are a family of bilobal glycoproteins that tightly bind
      ferric iron. Each of the homologous N- and C-lobes contains a single iron-binding
      site situated in a deep cleft. Human serum transferrin (hTF) serves as the iron
      transport protein in the blood; circulating transferrin binds to receptors on the
      cell surface, and the complex is internalized by endocytosis. Within the cell, a
      reduction in pH leads to iron release from hTF in a receptor-dependent process
      resulting in a large conformational change in each lobe. In the hTF N-lobe, two
      critical lysines facilitate this pH-dependent conformational change allowing
      entry of a chelator to capture the iron. In the C-lobe, the lysine pair is
      replaced by a triad of residues: Lys534, Arg632, and Asp634. Previous studies
      show that mutation of any of these triad residues to alanine results in
      significant retardation of iron release at both pH 7.4 and pH 5.6. In the present
      work, the role of the three residues is probed further by conversion to the
      residues observed at the equivalent positions in ovotransferrin (Q-K-L) and human
      lactoferrin (K-N-N) as well as a triad with an interchanged lysine and arginine
      (K534R/R632K). As expected, all of the constructs bind iron and associate with
      the receptor with nearly the same K(D) as the wild-type monoferric hTF control.
      However, interesting differences in the effect of the substitutions on the iron
      release rate in the presence and absence of the receptor at pH 5.6 are observed.
      Additionally, titration with KCl indicates that position 632 must have a
      positively charged residue to elicit a robust rate acceleration as a function of
      increasing salt. On the basis of these observations, a model for iron release
      from the hTF C-lobe is proposed. These studies provide insight into the
      importance of charge and geometry of the amino acids at these positions as a
      partial explanation for differences in behavior of individual TF family members,
      human serum transferrin, ovotransferrin, and lactoferrin. The studies
      collectively highlight important features common to both the N- and C-lobes of TF
      and the critical role of the receptor in iron release.

PMID- 16300394
TI  - Lipid-protein interactions of growth factor receptor-bound protein 14 in insulin
      receptor signaling.
AB  - Many retinal degenerative diseases show an early loss of rod cells followed by
      cone cells. In these degenerations the pathological phenotype is apoptosis. We
      have previously demonstrated the light-dependent tyrosine phosphorylation of the
      insulin receptor in the retina, which leads to the activation of anti-apoptotic
      signaling molecules. The mechanism of the regulation of the insulin receptor in
      the retina is not known. Yeast two-hybrid screening of a bovine retinal cDNA
      library with the cytoplasmic domain of the retinal insulin receptor (IRbeta)
      identified a member of the Grb7 (growth factor receptor-bound protein 7) gene
      family, Grb14. In this report, we describe the unique features of Grb14. Grb14
      forms a specific complex with the cytoplasmic domain of IRbeta when both are
      expressed as hybrid proteins in yeast cells. This interaction is strictly
      dependent upon receptor tyrosine kinase activity. Deletion mutagenesis on Grb14
      indicated a phosphorylated insulin receptor interacting (PIR) domain between the
      PH (pleckstrin homology) and SH2 (Src homology) domains that binds to IRbeta.
      Nuclear import assays in yeast indicated the presence of a functional nuclear
      localization signal in Grb14 between amino acids 63 and 68 (RRKKD). Subcellular
      localization of isolated retinas probed with anti-Grb14 antibody further
      confirmed the presence of Grb14 in nuclear fractions. Analysis using a protein
      lipid overlay assay indicated binding of Grb14 and its PH domain to D3
      phosphoinositides. In addition, Grb14-phosphoinositide 3,4,5-trisphosphate
      complexes are detected in lysates prepared from insulin-stimulated retina
      tissues, whereas Grb14-phosphoinositide 4,5-bisphosphate interactions are
      observed under non-insulin stimulated conditions. These findings suggest that
      Grb14 could be a diverse regulator of insulin receptor mediated pathways in the
      retina.

PMID- 16300395
TI  - Molecular mechanism of inhibition of nonclassical FGF-1 export.
AB  - Fibroblast growth factor (FGF-1) lacks a signal sequence and is exported by an
      unconventional release mechanism. The nonclassical export of FGF-1 has been shown
      to be inhibited by an anti-allergic and anti-inflammatory drug, amlexanox (AMX).
      We investigate the molecular mechanism(s) underlying the inhibitory action of AMX
      on the release of FGF-1, using a variety of biophysical techniques including
      multidimensional NMR spectroscopy. AMX binds to FGF-1 and enhances its
      conformational stability. AMX binds to locations close to Cys30 and sterically
      blocks Cu(2+)-induced oxidation, leading to the formation of the homodimer of FGF
      1. AMX-induced inhibition of the formation of the FGF-1 homodimer is observed
      both under cell-free conditions and in living cells. Results of this study
      suggest a novel approach for the design of drugs against FGF-1-mediated
      disorders.

PMID- 16300396
TI  - Mechanism of chaperone-like activity. Suppression of thermal aggregation of betaL
      crystallin by alpha-crystallin.
AB  - Thermal denaturation and aggregation of beta(L)-crystallin from bovine lens have
      been studied using differential scanning calorimetry (DSC) and dynamic light
      scattering (DLS). According to the DLS data, the distribution of the beta(L)
      crystallin aggregates by their hydrodynamic radius (R(h)) remains monomodal to
      the point of precipitating aggregates (sodium phosphate, pH 6.8; 100 mM NaCl; 60
      degrees C). The size of the start aggregates (R(h,0)) and duration of the latent
      stage (t(0)) leading to the formation of the start aggregates have been
      determined from the light scattering intensity versus the hydrodynamic radius
      plots and the dependences of R(h) on time. The R(h,0) value remains constant at
      variation of the beta(L)-crystallin concentration, whereas the t(0) value
      increases with diminishing beta(L)-crystallin concentration. The suppression of
      beta(L)-crystallin aggregation by alpha-crystallin is connected with the decrease
      in the R(h,0) value and increase in the t(0) value. In the presence of alpha
      crystallin the aggregate population is split into two components. The first
      component is represented by stable aggregates whose size remains constant in
      time. The aggregates of the other kind grow until they reach the size
      characteristic of aggregates prone to precipitation. The DSC data show that alpha
      crystallin has no appreciable influence on thermal denaturation of beta(L)
      crystallin.

PMID- 16300397
TI  - Dissecting the roles of a strictly conserved tyrosine in substrate recognition
      and catalysis by pseudouridine 55 synthase.
AB  - Sequence alignment of the TruA, TruB, RsuA, and RluA families of pseudouridine
      synthases (PsiS) identifies a strictly conserved aspartic acid, which has been
      shown to be the critical nucleophile for the PsiS-catalyzed formation of
      pseudouridine (Psi). However, superposition of the representative structures from
      these four families of enzymes identifies two additional amino acids, a lysine or
      an arginine (K/R) and a tyrosine (Y), from a K/RxY motif that are structurally
      conserved in the active site. We have created a series of Thermotoga maritima and
      Escherichia coli pseudouridine 55 synthase (Psi55S) mutants in which the
      conserved Y is mutated to other amino acids. A new crystal structure of the T.
      maritima Psi55S Y67F mutant in complex with a 5FU-RNA at 2.4 A resolution
      revealed formation of 5-fluoro-6-hydroxypseudouridine (5FhPsi), the same product
      previously seen in wild-type Psi55S-5FU-RNA complex structures. HPLC analysis
      confirmed efficient formation of 5FhPsi by both Psi55S Y67F and Y67L mutants but
      to a much lesser extent by the Y67A mutant when 5FU-RNA substrate was used.
      However, both HPLC analysis and a tritium release assay indicated that these
      mutants had no detectable enzymatic activity when the natural RNA substrate was
      used. The combined structural and mutational studies lead us to propose that the
      side chain of the conserved tyrosine in these four families of PsiS plays a dual
      role within the active site, maintaining the structural integrity of the active
      site through its hydrophobic phenyl ring and acting as a general base through its
      OH group for the proton abstraction required in the last step of PsiS-catalyzed
      formation of Psi.

PMID- 16300398
TI  - Identification of a specific inhibitor of the dishevelled PDZ domain.
AB  - The Wnt signaling pathways are involved in embryo development as well as in
      tumorigenesis. Dishevelled (Dvl) transduces Wnt signals from the receptor
      Frizzled (Fz) to downstream components in canonical and noncanonical Wnt
      signaling pathways. The Dvl PDZ domain is thought to play an essential role in
      both pathways, and we recently demonstrated that the Dvl PDZ domain binds
      directly to Fz receptors. In this study, using structure-based virtual ligand
      screening, we identified an organic molecule (NSC668036) from the National Cancer
      Institute small-molecule library that can bind to the Dvl PDZ domain. We then
      used molecular dynamics simulation to analyze the binding between the PDZ domain
      and NSC668036 in detail. In addition, we showed that, in Xenopus, as expected,
      NSC668036 inhibited the signaling induced by Wnt3A. This compound provides a
      basis for rational design of high-affinity inhibitors of the PDZ domain, which
      can block Wnt signaling by interrupting the Fz-Dvl interaction.

PMID- 16300399
TI  - Solution structure and interaction of the antimicrobial polyphemusins with lipid
      membranes.
AB  - The horseshoe crab cationic antimicrobial peptide polyphemusin I is highly active
      in vitro but not protective in mouse models of bacterial and LPS challenge, while
      a synthetic polyphemusin variant, PV5, was previously shown to be protective in
      vivo. In this study, we investigated the interaction of these peptides with lipid
      membranes in an effort to propose a mechanism of interaction. The solution
      structure of PV5 was determined by proton NMR in the absence and presence of
      dodecylphosphocholine (DPC) micelles. Like polyphemusin I, PV5 is a beta-hairpin
      but appeared less amphipathic in solution. Upon association with DPC micelles,
      PV5 underwent side chain rearrangements which resulted in an increased
      amphipathic conformation. Using fluorescence spectroscopy, both peptides were
      found to have limited affinity for neutral vesicles composed of
      phosphatidylcholine (PC). Incorporation of 25 mol % cholesterol or
      phosphatidylethanolamine into PC vesicles produced little change in the
      partitioning of either peptide. Incorporation of 25 mol % phosphatidylglycerol
      (PG) into PC vesicles, a simple prokaryotic model, resulted in a large increase
      in the affinity for both peptides, but the partition coefficient for PV5 was
      almost twice that of polyphemusin I. Differential scanning calorimetry studies
      supported the partitioning data and demonstrated that neither peptide interacted
      readily with neutral PC vesicles. Both peptides showed affinity for negatively
      charged membranes incorporating PG. The affinity of PV5 was much greater as the
      pretransition peak was absent at low peptide to lipid ratios (1:400) and the
      reduction in enthalpy of the main transition was greater than that produced by
      polyphemusin I. Both peptides decreased the lamellar to inverted hexagonal phase
      transition temperature of PE indicating the induction of negative curvature
      strain. These results, combined with previous findings that polyphemusin I
      promotes lipid flip-flop but does not induce significant vesicle leakage, ruled
      out the torroidal pore and carpet mechanisms of antimicrobial action for these
      polyphemusins.

PMID- 16300400
TI  - High-yield functional expression of human sodium/d-glucose cotransporter1 in
      Pichia pastoris and characterization of ligand-induced conformational changes as
      studied by tryptophan fluorescence.
AB  - Studies on the structure-function relationship of transporters require the
      availability of sufficient amounts of the protein in a functional state. In this
      paper, we report the functional expression, purification, and reconstitution of
      the human sodium/d-glucose cotransporter1 (hSGLT1) in Pichia pastoris and ligand
      induced conformational changes of hSGLT1 in solution as studied by intrinsic
      tryptophan fluorescence. hSGLT1 gene containing FLAG tag at position 574 was
      cloned into pPICZB plasmid, and the resulting expression vector pPICZB-hSGLT1 was
      introduced into P. pastoris strain GS115 by electroporation. Purification of
      recombinant hSGLT1 by nickel-affinity chromatography yields about 3 mg of
      purified recombinant hSGLT1 per 1-liter of cultured Pichia cells. Purified hSGLT1
      migrates on SDS-PAGE with an apparent mass of 55 kDa. Kinetic analysis of hSGLT1
      in proteoliposomes revealed sodium-dependent, secondary active, phlorizin
      sensitive, and stereospecific alpha-methyl-d-glucopyranoside transport,
      demonstrating its full catalytic activity. The position of the maximum intrinsic
      tryptophan fluorescence and titration with hydrophilic collisional quenchers KI,
      acrylamide, and trichloroethanol suggested that most of Trps in hSGLT1 in
      solution are in a hydrophobic environment. In the presence of sodium, sugars that
      have been identified earlier as substrate for the transporter increase intrinsic
      fluorescence in a saturable manner by a maximum of 15%. alpha-Methyl-d
      glucopyranoside had the highest affinity (K(d) = 0.71 mM), followed by d-glucose,
      d-galactose, d-mannose, and d-allose which showed a much lower affinity. l
      Glucose was without effect. d-Glucose also increased the accessibility of the
      Trps to hydrophilic collisional quenchers. On the contrary phlorizin, the well
      established inhibitor of SGLT1, decreased intrinsic fluorescence by a maximum of
      50%, and induced a blue shift of maximum (5 nm). Again, the effects were sodium
      dependent and saturable and a high affinity K(d) of 5 muM was observed. In
      addition the surface of hSGLT1 was labeled with 1-anilinonaphthalene-8-sulfonic
      acid, a reporter molecule for the surface hydrophobicity. In the presence of
      sodium, addition of d-glucose decreased ANS fluorescence whereas phlorizin
      increased ANS fluorescence. Thus three conformational states of SGLT1 could be
      defined which differ in their packing density and hydrophobicity of their
      surface. They reflect properties of the empty carrier, the d-glucose loaded
      carrier facing the outside of membrane and the complex of the outside-orientated
      carrier with phlorizin.

PMID- 16300401
TI  - The pathway by which the tetrameric protein transthyretin dissociates.
AB  - The homotetrameric protein transthyretin (TTR) must undergo rate-limiting
      dissociation to its constituent monomers in order to enable partial denaturation
      that allows the process of amyloidogenesis associated with human pathology to
      ensue. The TTR quaternary structure contains two distinct dimer interfaces, one
      of which creates the two binding sites for the natural ligand thyroxine. Tetramer
      dissociation could proceed through three distinct pathways; scission into dimers
      along either of the two unique quaternary interfaces followed by dimer
      dissociation represents two possibilities. Alternatively, the tetramer could lose
      monomers sequentially. To elucidate the TTR dissociation pathway, we employed two
      different TTR constructs, each featuring covalent attachment of proximal
      subunits. We demonstrate that tethering the A and B subunits of TTR with a
      disulfide bond (as well as the symmetrically disposed C and D subunits) allows
      urea-mediated dissociation of the resulting (TTR-S-S-TTR)(2) construct, affording
      (TTR-S-S-TTR)(1) retaining a stable 16-stranded beta-sheet structure that is
      equivalent to the dimer not possessing a thyroid binding site. In contrast,
      linking the A and C subunits employing a peptide tether (TTR-L-TTR)(2) affords a
      kinetically stable quaternary structure that does not dissociate or denature in
      urea. Both tethered constructs and wild-type TTR exhibit analogous stability
      based on guanidine hydrochloride denaturation curves. The latter denaturant can
      denature the tetramer, unlike urea, which can only denature monomeric TTR; hence
      urea requires dissociation to monomers to function. Under native conditions, the
      (TTR-S-S-TTR)(2) construct is able to dissociate and incorporate subunits from
      labeled WT TTR homotetramers at a rate equivalent to that exhibited by WT TTR. In
      contrast, the (TTR-L-TTR)(2) construct is unable to exchange any subunits, even
      after 180 h. All of the data presented herein and elsewhere demonstrate that the
      pathway of TTR tetramer dissociation occurs by scission of the tetramer along the
      crystallographic C(2) axis affording AB and CD dimers that rapidly dissociate
      into monomers. Determination of the mechanism of dissociation provides an
      explanation for why small molecules that bind at the AB/CD dimer-dimer interface
      impose kinetic stabilization upon TTR and disease-associated variants thereof.

PMID- 16300402
TI  - Methionine oxidation interferes with conversion of the prion protein into the
      fibrillar proteinase K-resistant conformation.
AB  - In recent studies, we developed a protocol for in vitro conversion of full-length
      mouse recombinant PrP (Mo rPrP23-230) into amyloid fibrils [Bocharova et al.
      (2005) J. Mol. Biol. 346, 645-659]. Because amyloid fibrils produced from
      recombinant Mo PrP89-230 display infectivity [Legname et al. (2004) Science 305,
      673-676], polymerizatiom of rPrPs in vitro represents a valuable model for
      elucidating the mechanism of prion conversion. Unexpectedly, when the same
      conversion protocol was used for hamster (Ha) rPrP23-231, we experienced
      substantial difficulties in forming fibrils. While searching for potential
      reasons of our failure to produce fibrils, we probed the effect of methionine
      oxidation in rPrP. We found that oxidation of methionines interferes with the
      formation of rPrP fibrils and that this effect is more profound for Ha than for
      Mo rPrP. To minimize the level of spontaneous oxidation, we developed a new
      protocol for rPrP purification, in which highly amyloidogenic Ha rPrP with
      minimal levels of oxidized residues was produced. Furthermore, our studies
      revealed that oxidation of methionines in preformed fibrils inhibited subsequent
      maturation of fibrils into proteinase K-resistant PrP(Sc)-like conformation (PrP
      res). Our data are consistent with the proposition that conformational changes
      within the central region of the protein (residues 90-140) are essential for
      adopting PrP-res conformation and demonstrate that methionine oxidation
      interferes with this process. These studies provide new insight into the
      mechanism of prion polymerization, solve a long-standing practical problem in
      producing PrP-res fibrils from full-length PrP, and may help in identifying new
      genetic and environmental factors that modulate prion disease.

PMID- 16300403
TI  - An inhibitor of TRPV1 channels isolated from funnel Web spider venom.
AB  - Capsaicin receptor channels (TRPV1) are nonselective cation channels that
      integrate multiple noxious stimuli in sensory neurons. In an effort to identify
      new inhibitors of these channels we screened a venom library for activity against
      TRPV1 channels and found robust inhibitory activity in venom from Agelenopsis
      aperta, a north American funnel web spider. Fractionation of the venom using
      reversed-phase HPLC resulted in the purification of two acylpolyamine toxins,
      AG489 and AG505, which inhibit TRPV1 channels from the extracellular side of the
      membrane. The activity of AG489 was characterized further, and the toxin was
      found to inhibit TRPV1 channels with a K(i) of 0.3 microM at -40 mV. Inhibition
      of TRPV1 channels by AG489 is strongly voltage-dependent, with relief of
      inhibition at positive voltages, consistent with the toxin inhibiting the channel
      through a pore-blocking mechanism. We used scanning mutagenesis throughout the
      TM5-TM6 linker, a region thought to form the outer pore of TRPV1 channels, to
      identify pore mutations that alter toxin affinity. Four mutants dramatically
      decrease toxin affinity and several mutants increase toxin affinity, consistent
      with the notion that the TM5-TM6 linker forms the outer vestibule of TRPV1
      channels and that AG489 is a pore blocker.

PMID- 16300404
TI  - Structural comparison of the unstable drkN SH3 domain and a stable mutant.
AB  - The N-terminal SH3 domain of the Drosophila adapter protein Drk (drkN SH3 domain)
      is marginally stable (DeltaG(U) = 1 kcal/mol) and exists in equilibrium between
      folded and highly populated unfolded states. The single substitution T22G,
      however, completely stabilizes the protein (DeltaG(U) = 4.0 kcal/mol). To probe
      the causes of instability of the wild-type (WT) protein and the dramatic
      stabilization of the mutant, we determined and compared nuclear magnetic
      resonance structures of the folded WT and mutant drkN SH3 domains. Residual
      dipolar coupling (RDC) and carbonyl chemical-shift anisotropy (C'-CSA) restraints
      measured for the WT and T22G domains were used for calculating the structures.
      The structures for the WT and mutant are highly similar. Thr22 of the WT and
      Gly22 of the mutant are at the i + 2 position of the diverging, type-II beta
      turn. Interestingly, not only Gly22 but also Thr22 successfully adopt an alpha(L)
      conformation, required at this position of the turn, despite the fact that
      positive phi values are energetically unfavorable and normally disallowed for
      threonine residues. Forcing the Thr22 residue into this unnatural conformation
      increases the free energy of the folded state of the WT domain relative to its
      T22G mutant. Evidence for residual helix formation in the diverging turn region
      has been previously reported for the unfolded state of the WT drkN SH3 domain,
      and this, in addition to other residual structure, has been proposed to play a
      role in decreasing the free energy of the unfolded state of the protein. Together
      these data provide evidence that both increasing the free energy of the folded
      state and decreasing the free energy of the unfolded state of the protein
      contribute to instability of the WT drkN SH3 domain.

PMID- 16300405
TI  - Interactions of thrombin with fibrinogen adsorbed on methyl-, hydroxyl-, amine-,
      and carboxyl-terminated self-assembled monolayers.
AB  - We have examined the initial phase of fibrin formation, thrombin-catalyzed
      fibrinopeptide cleavage, from adsorbed fibrinogen using surface plasmon resonance
      and liquid chromatography-mass spectrometry. Fibrinogen adsorption impaired
      thrombin-fibrinogen interactions compared to the interactions of thrombin with
      fibrinogen in solution. The properties of the underlying substrate significantly
      affected the extent and kinetics of fibrinopeptide cleavage, and the conversion
      of adsorbed fibrinogen to fibrin. Fibrinogen adsorbed on negatively charged
      surfaces (carboxyl-terminated self-assembled monolayers) released a smaller
      amount of fibrinopeptides, at a reduced rate relative to those of hydrophobic,
      hydrophilic, and positively charged surfaces (methyl-, hydroxyl-, and amine
      terminated self-assembled monolayers, respectively). Additionally, the conversion
      of adsorbed fibrinogen to fibrin was comparatively inefficient at the negatively
      charged surface. These data correlated well with trends previously reported for
      fibrin proliferation as a function of surface properties. We conclude that
      thrombin interactions with adsorbed fibrinogen determine the extent of subsequent
      fibrin proliferation on surfaces.

PMID- 16300406
TI  - Photoaffinity cross-linking of the corticotropin-releasing factor receptor type 1
      with photoreactive urocortin analogues.
AB  - Interaction of natural peptide ligands with class 2 GPCRs, which are targets of
      biologically important hormones such as glucagon, secretin, and corticotropin
      releasing factor (CRF), occurs with a common orientation, in that the ligand C
      terminus binds to the extracellular receptor N-terminus, whereas the ligand N
      terminus binds to the receptor juxtamembrane domain. N-Terminal truncation, by
      eight amino acids in the case of CRF, leads to antagonists, suggesting those
      residues constitute the receptor activating sequence. Here, we identified by
      photoaffinity cross-linking using p-benzoyl-l-phenylalanine (Bpa) analogues of
      urocortin (Ucn) the most affine CRF receptor agonist, interaction domains of
      CRF(1) receptor with Bpa residues at exclusive positions. Specific cleavage
      patterns of the corresponding ligand-receptor complexes, obtained using several
      cleavage methods in combination with SDS-PAGE for fragment size determination,
      showed that a Bpa group located N-terminally or in position 12 binds at the
      second and such in position 17 or 22 at the first extracellular receptor loop.
      Our results indicate that the very N-terminal ligand residues (1-11), which are
      responsible for receptor activation, are oriented to the juxtamembrane domain by
      interaction of amino acid residues 12, 17, and 22. Our findings contradict a
      recently proposed interaction model derived from ligand interaction with a
      soluble receptor N-terminus, indicating that conclusions drawn from such a
      reduced system may be of limited value to understand the interaction with the
      full-length receptor.

PMID- 16300407
TI  - Structural insights into the beta-xylosidase from Trichoderma reesei obtained by
      synchrotron small-angle X-ray scattering and circular dichroism spectroscopy.
AB  - The enzyme beta-xylosidase from Trichoderma reesei, a member of glycosil
      hydrolase family 3 (GH3), is a glycoside hydrolase which acts at the glycosidic
      linkages of 1,4-beta-xylooligosaccharides and that also exhibits alpha-l
      arabinofuranosidase activity on 4-nitrophenyl alpha-l-arabinofuranoside. In this
      work, we show that the enzyme forms monomers in solution and derive the low
      resolution molecular envelope of the beta-xylosidase from small-angle X-ray
      scattering (SAXS) data using the ab initio simulated annealing algorithm. The
      radius of gyration and the maximum dimension of the beta-xylosidase are 30.3 +/-
      0.2 and 90 +/- 5 A, respectively. In contrast to the fold of the only two
      structurally characterized members of GH3, the barley beta-d-glucan exohydrolase
      and beta-hexosaminidase from Vibrio cholerae, which have respectively two or one
      distinct domains, the shape of the beta-xylosidase indicates the presence of
      three distinct structural modules. Domain recognition algorithms were used to
      show that the C-terminal part of the amino acid sequence of the protein forms the
      third domain. Circular dichroism spectroscopy and secondary structure prediction
      programs demonstrate that this additional domain adopts a predominantly beta
      conformation.

PMID- 16300408
TI  - Herpes simplex virus 1 primase employs watson-crick hydrogen bonding to identify
      cognate nucleoside triphosphates.
AB  - We utilized NTP analogues containing modified bases to probe the mechanism of NTP
      selection by the primase activity of the herpes simplex virus 1 helicase-primase
      complex. Primase readily bound NTP analogues of varying base shape,
      hydrophobicity, and hydrogen-bonding capacity. Remarkably, primase strongly
      discriminated against incorporating virtually all of the analogues, even though
      this enzyme misincorporates natural NTPs at frequencies as high as 1 in 7. This
      included analogues with bases much more hydrophobic than a natural base (e.g., 4-
      and 7-trifluoromethylbenzimidazole), a base of similar hydrophobicity as a
      natural base but with the Watson-Crick hydrogen-bonding groups in unusual
      positions (7-beta-d-guanine), bases shaped almost identically to the natural
      bases (4-aminobenzimidazole and 4,6-difluorobenzimidazole), bases shaped very
      differently than a natural base (e.g., 5- and 6-trifluoromethylbenzimidazole),
      and bases capable of forming just one Watson-Crick hydrogen bond with the
      template base (purine and 4-aminobenzimidazole). The only analogues that primase
      readily polymerized into primers (ITP and 3-deaza-ATP) were those capable of
      forming Watson-Crick hydrogen bonds with the template base. Thus, herpes primase
      appears to require the formation of Watson-Crick hydrogen bonds in order to
      efficiently polymerize a NTP. In contrast to primase's narrow specificity for NTP
      analogues, the DNA-dependent NTPase activity associated with the herpes primase
      helicase complex exhibited very little specificity with respect to NTPs
      containing unnatural bases. The implications of these results with respect to the
      mechanism of the helicase-primase and current fidelity models are discussed.

PMID- 16300409
TI  - Initiator tRNA binding by e/aIF5B, the eukaryotic/archaeal homologue of bacterial
      initiation factor IF2.
AB  - To carry initiator Met-tRNA(i)(Met) to the small ribosomal subunit, eukaryal and
      archaeal cells use a heterotrimeric factor called e/aIF2. These cells also
      possess a homologue of bacterial IF2 called e/aIF5B. Several results indicate
      that the mode of action of e/aIF5B resembles some function of bacterial IF2. The
      e/aIF5B factor promotes the joining of ribosomal subunits. Moreover, there is
      genetic evidence that the factor participates in the binding of initiator tRNA to
      the small ribosomal subunit. However, up to now, an interaction between e/aIF5B
      and initiator tRNA was not evidenced. In this study, we use an assay based on
      protection of aminoacyl-tRNA against spontaneous deacylation to demonstrate that
      archaeal aIF5B indeed can interact with initiator tRNA. In complex formation,
      aIF5B shows specificity toward the methionyl moiety of the ligand. The complex
      between Saccharomyces cerevisiae eIF5B and methionylated initiator tRNA is less
      stable than that formed with aIF5B. In addition, this complex is almost
      indifferent to the side chain of the esterified amino acid. These results support
      the idea that, beyond the channeling of Met-tRNA(i)(Met) to the 40S subunit by
      e/aIF2, e/aIF5B comes to interact with initiator tRNA on the ribosome.
      Recognition of an aminoacylated tRNA species at this site would then allow
      translation to begin. In the case of archaea, this checkpoint would also include
      the verification of the presence of a methionine at the P site.

PMID- 16300410
TI  - CLAC binds to aggregated Abeta and Abeta fragments, and attenuates fibril
      elongation.
AB  - Deposition of amyloid beta-peptide (Abeta) into amyloid plaques is one of the
      invariant neuropathological features of Alzheimer's disease. Proteins that
      codeposit with Abeta are potentially important for the pathogenesis, and a
      recently discovered plaque-associated protein is the collagenous Alzheimer
      amyloid plaque component (CLAC). In this study, we investigated the molecular
      interactions between Abeta aggregates and CLAC using surface plasmon resonance
      spectroscopy and a solid-phase binding immunoassay. We found that CLAC binds to
      Abeta with high affinity, that the central region of Abeta is necessary and
      sufficient for CLAC interaction, and that the aggregation state of Abeta as well
      as the presence of negatively charged residues is important. We also show that
      this binding results in a reduced rate of fibril elongation. Taken together, we
      suggest that CLAC becomes involved at an intermediate stage in the pathogenesis
      by binding to Abeta fibrils, including fibrils formed from peptides with
      truncated N- or C-termini, and thereby slows their growth.

PMID- 16300411
TI  - Elafin and its precursor trappin-2 still inhibit neutrophil serine proteinases
      when they are covalently bound to extracellular matrix proteins by tissue
      transglutaminase.
AB  - Elafin and its precursor trappin-2 (also called pre-elafin) are potent protein
      inhibitors of neutrophil serine proteases such as leukocyte elastase and
      proteinase 3. Trappin-2 has unique conserved sequence motifs rich in Gln and Lys
      residues. These motifs are substrates for transglutaminases that may enable
      trappin-2 to be cross-linked to extracellular matrix proteins, thus anchoring the
      inhibitor at its site of action. We have used Western blotting and ELISA-based
      assays to demonstrate that both elafin and trappin-2 can be conjugated to various
      extracellular matrix proteins in vitro by a type 2 transglutaminase. Cross-linked
      elafin and trappin-2 still inhibited their target proteases. Surface plasmon
      resonance studies allowed the determination of the kinetic constants governing
      the interaction of fibronectin-bound elafin and trappin-2 with neutrophil
      elastase and proteinase 3. Both inhibitors were potent inhibitors when cross
      linked to fibronectin by transglutamination, with equilibrium dissociation
      constants K(i) for their interaction with target proteases of 0.3 nM (elastase
      elafin), 20 nM (proteinase 3-elafin), 0.3 nM (elastase-trappin-2), and 12 nM
      (proteinase 3-trappin-2). The conjugated inhibitors reacted more slowly with
      their target enzymes than did the soluble inhibitors, perhaps due to their
      immobilization, with association rate constants of 2-7 x 10(5) M(-)(1) s(-)(1)
      for elastase and 1-4 x 10(4) M(-)(1) s(-)(1) for proteinase 3. We believe this is
      the first demonstration that transglutaminase-mediated cross-linking of serine
      protease inhibitors to proteins preserves their inhibitory capacities.

PMID- 16300412
TI  - Analysis of the specificity of sialyltransferases toward mucin core 2, globo, and
      related structures. identification of the sialylation sequence and the effects of
      sulfate, fucose, methyl, and fluoro substituents of the carbohydrate chain in the
      biosynthesis of selectin and siglec ligands, and novel sialylation by cloned
      alpha2,3(O)sialyltransferase.
AB  - Sialic acids are key determinants in many carbohydrates involved in biological
      recognition. We studied the acceptor specificities of three cloned
      sialyltransferases (STs) [alpha2,3(N)ST, alpha2,3(O)ST, and alpha2,6(N)ST] and
      another alpha2,3(O)ST present in prostate cancer cell LNCaP toward mucin core 2
      tetrasaccharide [Galbeta1,4GlcNAcbeta1,6(Galbeta1,3)GalNAcalpha-O-Bn] and Globo
      [Galbeta1,3GalNAcbeta1,3Galalpha-O-Me] structures containing sialyl, fucosyl,
      sulfo, methyl, or fluoro substituents by identifying the products by electrospray
      ionization tandem mass spectral analysis and other biochemical methods. The Globo
      precursor was an efficient acceptor for both alpha2,3(N)ST and alpha2,3(O)ST,
      whereas only alpha2,3(O)ST used its deoxy analogue (d-Fucbeta1,3GalNAcbeta1,3-Gal
      alpha-O-Me); 2-O-MeGalbeta1,3GlcNAc and 4-OMeGalbeta1,4GlcNAc were specific
      acceptors for alpha2,3(N)ST. Other major findings of this study include: (i)
      alpha2,3 sialylation of beta1,3Gal in mucin core 2 can proceed even after
      alpha1,3 fucosylation of beta1,6-linked LacNAc. (ii) Sialylation of beta1,3Gal
      must precede the sialylation of beta1,4Gal for favorable biosynthesis of mucin
      core 2 compounds. (iii) alpha2,3 sialylation of the 6-O-sulfoLacNAc moiety in
      mucin core 2 (e.g., GlyCAM-1) is facilitated when beta1,3Gal has already been
      alpha2,3 sialylated. (iv) alpha2,6(N)ST was absolutely specific for the
      beta1,4Gal in mucin core 2. Either alpha1,3 fucosylation or 6-O-sulfation of the
      GlcNAc moiety reduced the activity. Sialylation of beta1,3Gal in addition to 6-O
      sulfation of GlcNAc moiety abolished the activity. (v) Prior alpha2,3 sialylation
      or 3-O-sulfation of beta1,3Gal would not affect alpha2,6 sialylation of
      Galbeta1,4GlcNAc of mucin core 2. (vi) A 3- or 4-fluoro substituent in beta1,4Gal
      resulted in poor acceptors for the cloned alpha2,6(N)ST and alpha2,3(N)ST,
      whereas 4-fluoro- or 4-OMe-Galbeta1,3GalNAcalpha was a good acceptor for cloned
      alpha2,3(O)ST. (vii) 4-O-Methylation of beta1,4Gal abolished the acceptor ability
      toward alpha2,6(N)ST but increased the acceptor efficiency considerably toward
      alpha2,3(N)ST. (viii) Just like LNCaPalpha1,2-FT and Gal-3-O-sulfotransferase T2,
      the cloned alpha2,3(N)ST which modifies terminal Gal in Galbeta1,4GlcNAc also
      efficiently utilizes the terminal beta1,3Gal in the Globo backbone. Utilization
      of C-3 blocked compounds such as 3-O-sulfo-Galbeta1,3GalNAcbeta1,3Galalpha-OMe as
      acceptors by cloned alpha2,3(O)ST and analyses of the resulting products by
      lectin chromatography and mass spectrometry indicate that alpha2,3(O)ST is
      capable of attaching NeuAc to another position in C-3-substituted beta1,3Gal.

PMID- 16300414
TI  - Functional amyloid formation within mammalian tissue.
AB  - Amyloid is a generally insoluble, fibrous cross-beta sheet protein aggregate. The
      process of amyloidogenesis is associated with a variety of neurodegenerative
      diseases including Alzheimer, Parkinson, and Huntington disease. We report the
      discovery of an unprecedented functional mammalian amyloid structure generated by
      the protein Pmel17. This discovery demonstrates that amyloid is a fundamental
      nonpathological protein fold utilized by organisms from bacteria to humans. We
      have found that Pmel17 amyloid templates and accelerates the covalent
      polymerization of reactive small molecules into melanin-a critically important
      biopolymer that protects against a broad range of cytotoxic insults including UV
      and oxidative damage. Pmel17 amyloid also appears to play a role in mitigating
      the toxicity associated with melanin formation by sequestering and minimizing
      diffusion of highly reactive, toxic melanin precursors out of the melanosome.
      Intracellular Pmel17 amyloidogenesis is carefully orchestrated by the secretory
      pathway, utilizing membrane sequestration and proteolytic steps to protect the
      cell from amyloid and amyloidogenic intermediates that can be toxic. While
      functional and pathological amyloid share similar structural features, critical
      differences in packaging and kinetics of assembly enable the usage of Pmel17
      amyloid for normal function. The discovery of native Pmel17 amyloid in mammals
      provides key insight into the molecular basis of both melanin formation and
      amyloid pathology, and demonstrates that native amyloid (amyloidin) may be an
      ancient, evolutionarily conserved protein quaternary structure underpinning
      diverse pathways contributing to normal cell and tissue physiology.

PMID- 16300415
TI  - CFH Y402H confers similar risk of soft drusen and both forms of advanced AMD.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of
      irreversible visual impairment in the developed world. The two forms of advanced
      AMD, geographic atrophy and neovascular AMD, represent different pathological
      processes in the macula that lead to loss of central vision. Soft drusen,
      characterized by deposits in the macula without visual loss, are considered to be
      a precursor of advanced AMD. Recently, it has been proposed that a common
      missense variant, Y402H, in the Complement Factor H (CFH) gene increases the risk
      for advanced AMD. However, its impact on soft drusen, GA, or neovascular AMD--or
      the relationship between them--is unclear. METHODS AND FINDINGS: We genotyped 581
      Icelandic patients with advanced AMD (278 neovascular AMD, 203 GA, and 100 with
      mixed neovascular AMD/GA), and 435 with early AMD (of whom 220 had soft drusen).
      A second cohort of 431 US patients from Utah, 322 with advanced AMD (244
      neovascular AMD and 78 GA) and 109 early-AMD cases with soft drusen, were
      analyzed. We confirmed that the CFH Y402H variant shows significant association
      to advanced AMD, with odds ratio of 2.39 in Icelandic patients (p = 5.9 x 10(
      12)) and odds ratio of 2.14 in US patients from Utah (p = 2.0 x 10(-9)) with
      advanced AMD. Furthermore, we show that the Y402H variant confers similar risk of
      soft drusen and both forms of advanced AMD (GA or neovascular AMD). CONCLUSION:
      Soft drusen occur prior to progression to advanced AMD and represent a
      histological feature shared by neovascular AMD and GA. Our results suggest that
      CFH is a major risk factor of soft drusen, and additional genetic factors and/or
      environmental factors may be required for progression to advanced AMD.

PMID- 16300416
TI  - Health care resources and costs for treating peripheral artery disease in a
      managed care population: results from analysis of administrative claims data.
AB  - OBJECTIVE: Peripheral arterial disease (PAD) is associated with high rates of
      morbidity and mortality and serves as an important marker for advanced systemic
      atherosclerosis accompanied by symptomatic or asymptomatic ischemia of the
      coronary, cerebral, and visceral vasculature. There are little published data on
      the use of health care resources and costs attributable to PAD. The objectives of
      this study were to evaluate, from a societal perspective, PAD-related health care
      resource utilization and to determine the total annualized costs and cost
      components for patients with PAD, with particular attention to the key outcomes
      of myocardial infarction (MI), transient ischemic attacks (TIA), stroke, and
      amputations. METHODS: This study examined medical, hospital and outpatient, and
      pharmacy claims from a large managed care database with dates of service from
      January 1, 1999, through August 31, 2003. Patients with PAD were identified from
      claims using International Classification of Diseases, Ninth Revision, Clinical
      Modification (ICD-9-CM) diagnosis codes (primary or secondary codes), ICD-9-CM
      procedure codes, current procedural terminology (CPT) codes, or by a pharmacy
      claim for cilostazol or pentoxifylline. The index date for each patient was the
      first occurrence of either a medical claim for PAD or a pharmacy claim for 1 of
      the 2 drugs. Patients were required to be a minimum of 18 years old with
      continuous plan eligibility. The prevalence of PAD in adults in a managed care
      setting was also determined, as were annual rates for the key outcomes of MI,
      TIA, stroke, and amputations. Health care resource utilization and costs were
      calculated for PAD patients after the index date for a period of at least 12
      months per patient for medications, outpatient/physician office visits,
      laboratory/diagnostic procedures, emergency department visits, and
      hospitalization. Cost was defined as the allowed charge on each administrative
      claim, including the amount paid by the insurer plus the amount paid by the
      health plan members (copay, deductible, and coinsurance). RESULTS: Prior to
      application of exclusion criteria for patients aged 18 years or older and the
      minimum period of continuous eligibility, the overall prevalence of PAD was 1.18%
      of the total managed care organization population.s 6.67 million members. The PAD
      study cohort consisted of 30,561 patients with a mean age of 70.7 years at index.
      The most common comorbidities identified in the preindex period for these PAD
      patients included hypertension (67% of patients); metabolic
      disorders/hypercholesterolemia (57%); heart disease including cardiomyopathy,
      dysrhythmias, and heart failure (55%); and ischemic heart disease (47%). Over a
      mean postindex period of 25.2 months (median 23.4 months), the total mean
      annualized PAD-related cost was $5,955 per patient per year (PPPY).
      Hospitalizations accounted for the largest component cost category, averaging
      $4,442 PPPY or 75% of the total annualized PAD-related cost per PAD patient. PAD
      related noncoronary procedures averaged $729 PPPY (12.2% of total annual PAD
      related costs), and PAD-related medications (including antihypertensives and
      lipid-lowering therapy) totaled $610 (10.2% of total annual costs), including
      $313 PPPY for antihypertensives and $207 for lipid-lowering therapy. For the
      subgroup of 24,075 newly identified PAD patients, 8,479 (35.2%) were hospitalized
      during an average 25.2 months of follow-up, with the mean time to first
      hospitalization of 8.9 months. CONCLUSIONS: Approximately 75% of the total PAD
      related patient cost in an average of 25 months of follow-up is contributed by
      hospital costs, and 35% of patients newly diagnosed with PAD experienced a
      hospitalization in a mean of 8.9 months after the index diagnosis. Based upon
      mean annual health and member costs of only $313 PPPY for antihypertensives and
      $207 for lipid-lowering therapy, drug therapy in PAD patients may be
      underutilized.

PMID- 16300417
TI  - Evaluation of omalizumab from a health plan perspective.
AB  - OBJECTIVE: To review the pathophysiology of allergic asthma and information on
      the pharmacology, clinical efficacy, safety profile, and direct drug costs for
      omalizumab to provide a basis for a defined role of this agent in allergic asthma
      therapy in managed care organizations. SUMMARY: Omalizumab is a monoclonal
      antibody targeting the high-affinity receptor binding site on human
      immunoglobulin E (IgE). When bound by omalizumab, IgE does not bind to basophils.
      As a result, degranulation is attenuated and allergic asthma symptoms are
      reduced. In asthma trials, omalizumab reduced inhaled corticosteroid and rescue
      medication requirements and improved asthma control and asthma quality of life in
      moderate-to-severe allergic asthmatics with disease poorly controlled by inhaled
      corticosteroids. Omalizumab has generally been well tolerated. However, injection
      site reactions occur in nearly 1 of every 2 patients, a problem that generally
      becomes less with continued dose administration. Severe injection site reactions
      are reported in 12% of patients. Other adverse events commonly reported in
      clinical trials include viral infections (23%), upper respiratory infections
      (20%), sinusitis (16%), headache (15%), and pharyngitis (11%). Because the
      acquisition cost of omalizumab is high (generally $15,000 to $44,000 per patient
      per year, before contractual discounts), its use is cost-prohibitive in all but
      the most severe, poorly controlled allergic asthmatic patients who are utilizing
      large amounts of emergency health care resources to manage exacerbations.
      Experience with use of this drug beyond 52 weeks is lacking. CONCLUSION: Although
      omalizumab has demonstrated efficacy and safety in adults and adolescents with
      uncontrolled moderate-to-severe allergic asthma, its use should be restricted to
      a narrowly defined population of allergic asthmatics who utilize large amounts of
      health care resources. If targeted only toward this population, cost-of-care
      studies suggest that the high cost of this product in these patients could be
      offset by savings resulting from the less frequent use of high-intensity medical
      services for asthma exacerbations. The use of omalizumab beyond 52 weeks needs
      evaluation.

PMID- 16300418
TI  - Product-line extensions and pricing strategies of brand-name drugs facing patent
      expiration.
AB  - OBJECTIVE: This study proposed an alternative to brand loyalty as the explanation
      for the continued price rigidity of patent-expired brand-name prescription drugs
      despite the increase in market entry of generic drugs facilitated by the 1984
      Drug Price Competition and Patent Term Restoration Act. Study hypotheses were to
      test (1) whether market entries of new-product extensions are associated with
      market success of original brand-name drugs before generic drug entry, and (2)
      whether original brand-name drugs exhibit price rigidity to generic entry only
      when they are extended. METHODS: The design is a retrospective follow-up study
      for the prescription drug brands that lost their patents between 1987 and 1992.
      The drug brands were limited to nonantibiotic, orally administered drugs
      containing only 1 active pharmaceutical ingredient. Information on patent
      expiration, entry of a product extension, and market success were determined from
      the U.S. Food and Drug Administration.s Orange Book, First DataBank, and American
      Druggist, respectively. Market success was defined as whether an original drug
      brand was listed in the top 100 prescriptions most frequently dispensed before
      facing generic entry. Product-line extension was defined as the appearance of
      another product that a company introduces within the same market after its
      existing product. Drug prices were average wholesale prices from the Drug Topics
      Red Book. The relationship between product-line extension and market success was
      examined using a logistic regression analysis. The price rigidity to entry was
      tested using a panel regression analysis. RESULTS: A total of 27 drug brands lost
      their patents between 1987 and 1992. Drug brands that achieved market success
      were 16 times more likely to be extended than were those that did not (OR=16, 95%
      confidence interval, 2.12-120.65). The price rigidity to entry existed in drug
      brands with extensions (beta=2.65%, P <0.033), but not in those brands without
      extensions (beta=-2.40%, P <0.001). CONCLUSION: This study provided some support
      for the alternative explanation to brand loyalty that a new product-line
      extension introduced for an original brand helps the original price be rigid
      despite the entry of generic drugs facilitated by the 1984 Drug Price Competition
      and Patent Term Restoration Act.

PMID- 16300419
TI  - Effect of a clinical pharmacy education program on improvement in the quantity
      and quality of venous thromboembolism prophylaxis for medically ill patients.
AB  - OBJECTIVE: The American College of Chest Physicians (ACCP) recommends
      unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) for
      prevention of venous thromboembolism (VTE) in medically ill patients. Despite
      these recommendations, a previous analysis at our institution revealed a low
      utilization of VTE prophylaxis in medically ill patients. Our objective was to
      evaluate the effects of a pharmacy-driven education program on the quantity and
      quality of VTE prophylaxis in medically ill patients. METHODS: An educational
      program focusing on the importance of VTE prophylaxis in medically ill patients
      was developed by clinical pharmacists and presented to nurses, pharmacists, and
      physicians in a 493-bed community teaching hospital. The educational program was
      conducted between June 2002 and June 2003 and consisted of in-service
      presentations, newsletters, and quality assurance presentations on VTE
      prophylaxis. The educational program focused on 4 main points: (1) hospitalized
      medically ill patients are at risk for developing VTE, (2) how to identify
      medically ill patients who require VTE prophylaxis, (3) the fact that VTE
      prophylaxis is currently underutilized in medically ill patients, and (4)
      appropriate VTE prophylaxis strategies for medically ill patients. A
      posteducation retrospective chart review was performed in medically ill patients
      with discharge dates between October 2003 and March 2004, and these posteducation
      medical chart data were compared with the results from a preeducation analysis of
      patents with discharge dates from January 2001 to March 2002. Data collection
      included patient demographics, VTE risk factors, and use and type of VTE
      prophylaxis. RESULTS: The posteducation retrospective chart review was performed
      for 297 medically ill patients with discharge dates between October 2003 and
      March 2004 and for 344 preeducation patients discharged between January 2001 and
      March 2002. Patient demographics and primary diagnoses were similar between the
      preeducation and posteducatin groups. The mean number of risk factors per patient
      in the preeducation group was 2.53 +/- 0.96 versus 2.38 +/- 0.88 in the
      posteducation group (P=0.626). Pharmacy education was associated with an increase
      in the utilization of any VTE prophylaxis (43% in the preperiod vs. 58% in the
      postperiod; P <0.001). Prophylaxis judged to be suitable (UFH 5,000 units twice
      daily, or UFH 5,000 units 3 times daily, or LMWH once daily), increased from 38%
      in the preeducation period to 49% in the posteducation period, P=0.006).
      Prophylaxis judged to be optimal (UFH 3 times daily or LMWH once daily) increased
      from 11% to 44% of patients, P <0.001). CONCLUSIONS: A hospital-wide clinical
      pharmacy education program was associated with significant improvement in the
      quantity and quality of VTE prophylaxis in medically ill patients in a community
      teaching hospital.

PMID- 16300420
TI  - Lipid levels and use of lipid-lowering drugs for patients in pharmacist-managed
      lipid clinics versus usual care in 2 VA Medical Centers.
AB  - OBJECTIVE: The objective of this study was to assess the effectiveness of
      pharmacist- managed dyslipidemia clinics at 2 Veterans Affairs medical centers
      since the release of the 2001 National Cholesterol Education Panel Adult
      Treatment Panel III (NCEP ATP III) guideline compared with the usual care (UC)
      provided by other health care professionals in the same setting. METHODS:
      Analysis was performed through retrospective chart review of patients with a
      diagnosis of dyslipidemia who received care in either the Amarillo or Lubbock,
      Texas, pharmacist-managed lipid clinics (LCs) or UC from a primary care
      physician. Data from medical charts were abstracted for dates of service from
      July 2001 to December 2003 for 115 patients selected randomly from LC rolls
      matched with 115 patients with a diagnosis of dyslipidemia selected randomly from
      UC. All patients had to have had at least 3 visits with the LC or 3 visits in UC
      with a billing code of dyslipidemia; they were followed for at least 6 months
      after an initial visit in July 2001 or thereafter and were enrolled in the VA
      health care system for at least 1 year. Baseline lipid values were available for
      LC but not UC patients. Cholesterol target goals were determined according to
      NCEP ATP III guideline. RESULTS: After an average of 21.6 months of follow-up,
      the proportion of patients in the LC group that attained goal level increased
      from 45.2% at baseline to 82.6% for total cholesterol (TC) and from 36.5% at
      baseline to 64.3% for lowdensity lipoprotein cholesterol (LDL-C [P <0.001 for
      both comparisons]). There was an average 24.5 mg/dL absolute reduction (relative
      reduction, 19.4%) in LDL-C along with significant improvements in the other lipid
      levels (P <0.001 for TC and LDL-C, P = 0.007 for triglycerides [TGs]) with the
      exception of highdensity lipoprotein cholesterol (HDL-C), which declined from
      40.0 mg/dL to 36.3 mg/dL (P <0.001). A total of 50 patients (43.5%) were on lipid
      lowering pharmacotherapy at baseline versus 108 patients (93.9%) at follow-up.
      Compared with UC, LC patients were more likely to have achieved goal LDL-C (64.3%
      vs. 15.7% for UC, P <0.001) and TC (82.6% vs. 40.9%, P <0.001), but there was no
      difference in the proportion of patients at TG goal for LC (65.2%) compared with
      UC (52.2%, P = 0.061) or at HDL-C goal (23.5% for LC vs. 33.0% for UC, P =
      0.143). A higher proportion of LC patients (93.9%) used lipid-lowering agents
      compared with UC patients (24.3%, P <0.001). Subanalysis of patients on a lipid
      lowering agent found that a significantly higher proportion (85.2%) in the LC
      group were at goal total cholesterol compared with 60.7% for UC (P = 0.012) and
      at goal LDL-C (66.7% for LC vs. 39.3% for UC, P = 0.016). However, a lower
      proportion were at goal HDL-C for LC (21.3%) versus 42.9% for UC (P = 0.043).
      Overall, only 11 LC patients (9.6%) attained goal levels for all 4 serum lipid
      values by the end of follow-up versus 2 UC patients (1.7%, P = 0.019).
      CONCLUSIONS: Nearly two thirds of patients diagnosed with dyslipidemia and
      enrolled in a pharmacist-managed LC had LDL-C levels at or below NCEP ATP III
      target goal compared with 16% of dyslipidemia patients who received UC from their
      primary care provider. The pharmacist-managed LC patients were also twice as
      likely (83 vs. 41%) to have attained the TC target goal, but there was no
      difference between the 2 groups in the proportion of patients who attained either
      TG or HDL-C target goals. Only 9.6% of LC patients were at goal for all 4
      individual lipid measures at the end of follow-up.

PMID- 16300421
TI  - Who Needs XR, LA, SR, XL, ER, or CR?

PMID- 16300422
TI  - Selectivity and specificity are the keys to cost-effective use of omalizumab for
      allergic asthma.

PMID- 16300423
TI  - Pharmacist intervention in safe and effective conversion of brand to generic
      drugs.

PMID- 16300424
TI  - Relationship of cocaine-induced c-Fos expression to behaviors and the role of
      serotonin 5-HT2A receptors in cocaine-induced c-Fos expression.
AB  - Serotonin 5-HT2A receptor antagonists have been shown to attenuate the locomotor
      stimulant effects of cocaine in rats. The present study used the expression of c
      Fos protein as a marker to identify brain areas through which 5-HT2A receptors
      may modulate cocaine-induced behaviors. Significant correlations were observed
      between cocaine-induced hyperactivity and c-Fos expression in the nucleus
      accumbens core (NAcC), caudate-putamen (CPu), and subthalamic nucleus. In a
      separate experiment, a low, behaviorally relevant dose of cocaine was found to
      increase c-Fos immunoreactivity in the medial CPu, NAcC, and nucleus accumbens
      shell (NAcSh). The selective 5-HT2A receptor antagonist M100907 significantly
      attenuated cocaine-induced c-Fos expression in the medial CPu and in the NAcSh.
      These data suggest that 5-HT2A receptors in the NAcSh and CPu or in afferents to
      these regions may contribute to genomic responses to cocaine in the brain as well
      as to cocaine-induced locomotor activity.

PMID- 16300425
TI  - Serotonin-1B receptor activity and expression modulate the aggression-stimulating
      effects of adolescent anabolic steroid exposure in hamsters.
AB  - Repeated high dose (5.0 mg/kg) anabolic-androgenic steroid (AAS) exposure during
      adolescence stimulates offensive aggression in male Syrian hamsters. These
      studies examined whether AAS-induced aggression was regulated by the activity of
      serotonin (5HT) type-1B receptors and correlated with altered 5HT1B expression.
      AAS-treated hamsters were tested for offensive aggression following the
      administration of the 5HT1B agonist anpirtoline (0.125-0.5 mg/kg). Anpirtoline
      dose-dependently reduced select components of the AAS-induced aggressive
      response, with significant reductions observed at 0.25 mg/kg. Aggressive, AAS
      treated hamsters showed significant decreases in the area covered by 5HT1B
      containing neuronal puncta and increases in the number of 5HT1B-containing
      neuronal somata in select brain regions implicated in aggression control.
      Together, these data support a role for site-specific alterations in 5HT1B
      signaling and expression in adolescent AAS-induced aggression.

PMID- 16300427
TI  - Combined dieting and stress evoke exaggerated responses to opioids in binge
      eating rats.
AB  - The authors developed an animal model of binge eating where history of caloric
      restriction with footshock stress (R + S) causes rats to consume twice the normal
      amount of palatable food. The authors tested the hypothesis that binge eating is
      mediated by changes in opioid control of feeding by comparing rats' anorectic and
      orexigenic responses to naloxone and butorphanol, respectively, and by testing
      the ability of butorphanol to elicit binge eating of chow when palatable food was
      absent. Mu/kappa opioid-receptor blockade and activation had exaggerated
      responses in the R + S rats with naloxone suppressing binge eating to control
      levels, and although butorphanol did not trigger chow binge eating, it enhanced
      binge eating of palatable food. These responses in sated normal-weight rats
      strengthen evidence that reward, over metabolic need, drives binge eating.

PMID- 16300426
TI  - Hyperphagia induced by GABAA receptor-mediated inhibition of the nucleus
      accumbens shell: dependence on intact neural output from the central amygdaloid
      region.
AB  - To investigate the role of corticolimbic input in modulating feeding-related
      nucleus accumbens (Acb) circuitry, researchers temporarily deactivated sites
      within the basolateral amygdaloid complex (BLA) or central amygdaloid region
      (CeA) via GABA(A) agonist (muscimol) infusions and measured feeding responses
      following muscimol infusions into the Acb shell. Hyperphagia elicited by intra
      Acb shell muscimol was not altered by coinfusions of intra-BLA muscimol. In
      contrast, muscimol infusions into the CeA dose-dependently reduced feeding
      elicited either by intra-Acb shell GABA(A) receptor stimulation or by food
      deprivation and produced a syndrome of forepaw treading. Intra-CeA tetrodotoxin
      infusions also blocked intra-Acb shell muscimol-induced hyperphagia. Hence,
      feeding elicited by intra-Acb shell GABA(A) receptor stimulation requires intact
      neural output from the CeA but not the BLA.

PMID- 16300428
TI  - Altered vulnerability to acute opiate withdrawal following stress: roles of N
      methyl-D-aspartate and glucocorticoid receptors.
AB  - Five experiments studied the modulation of acute opiate withdrawal by restraint
      stress. Rats were subjected to a 2-hr restraint stress, and 1, 3, or 7 days later
      they received a single injection of morphine followed by injection of naloxone.
      Naloxone precipitated a withdrawal syndrome. This syndrome was enhanced when it
      occurred 1 day after stress but was reduced when it occurred 7 days after stress.
      The enhancement of withdrawal by restraint stress was prevented by treatment with
      the N-methyl-d-aspartate (NMDA) receptor antagonist MK801 or the glucocorticoid
      receptor antagonist RU486 prior to stress. Together these experiments show that
      restraint stress alters vulnerability to opiate withdrawal and identify
      activation of NMDA and glucocorticoid receptors as causal to this vulnerability.

PMID- 16300429
TI  - A testosterone metabolite is rewarding to ovariectomized female rats.
AB  - Anabolic androgenic steroids have become a major class of drugs of abuse among a
      growing population of male and female adolescents. Although the rewarding and
      reinforcing properties of androgens have been demonstrated in male rodents, it is
      unknown whether these properties are apparent in female rats. In this study,
      conditioned place preference and self-administration paradigms showed that the
      endogenous androgen metabolite 3alphaDIOL is rewarding and reinforcing in
      ovariectomized female rats. Because 3alphaDIOL can be synthesized de novo in the
      brain, it is hypothesized that this neurosteroid provides a permissive
      neurochemical environment that modulates reward processes.

PMID- 16300430
TI  - Microlesions of the ventromedial nucleus of the hypothalamus: effects on
      sociosexual behaviors in male rats.
AB  - Electrolytic microlesions aimed at the dorsomedial portion of the ventromedial
      nucleus (VMN) of the hypothalamus were generated, and effects on copulation, 50
      kHz vocalizations, scent marking, and sexual motivation were measured. Male rats
      were tested before and after lesions, after castration, and after testosterone
      replacement. Three control groups were used: One received sham surgery, another
      received no surgery or testosterone replacement, and a 3rd received lesions
      primarily outside the VMN. VMN lesions produced impairments in testosterone's
      ability to restore ultrasonic vocalizations and scent marking, assessed with 2
      different test methods. Copulation, sexual motivation, and weight gain were
      largely unaffected, although some differences were observed in copulatory
      efficiency. The authors conclude that the integrity of the VMN is important for
      full expression of sociosexual behaviors in male rats.

PMID- 16300431
TI  - Lesions of the Edinger-Westphal nucleus alter food and water consumption.
AB  - The Edinger-Westphal nucleus (EW) produces several neuropeptides, including
      urocortin 1 and cocaine-amphetamine-regulated transcript, which regulate feeding,
      energy balance, and anxiety. Additionally, the EW projects to feeding and anxiety
      regulatory brain areas. The authors tested the effect of lesions of the EW on the
      consumption of food, water and flavored solutions, metabolic indices, and
      exploratory behavior on the elevated plus maze in male C57BL/6J mice. EW lesion
      significantly reduced basal and deprivation-induced food and fluid consumption
      compared with sham and placement controls, but it did not alter behavior on the
      elevated plus maze. EW lesion had no effect on indices of basal metabolic
      activity, including plasma glucose level and body temperature. These effects
      suggest that the peptidergic neurons of the EW regulate food consumption.

PMID- 16300432
TI  - Various aspects of feeding behavior can be partially dissociated in the rat by
      the incentive properties of food and the physiological state.
AB  - The authors investigated the role of food incentive properties and homeostatic
      state on the motivational, anticipatory, and consummatory aspects of feeding.
      Behavioral tests were carried out on food-sated and food-restricted rats that
      were presented with 2 kinds of food differing in their palatability level. Both
      food-sated and food-restricted rats consumed large quantities and were highly
      motivated when presented with very palatable food. In contrast, only food
      restricted rats developed anticipatory responses, regardless of the kind of food
      presented. These data suggest that food incentive properties play a key role in
      the control of consummatory and motivational components of feeding but seem less
      involved in the regulation of anticipatory behavior.

PMID- 16300433
TI  - Amygdalar unit activity during three learning tasks: eyeblink classical
      conditioning, Pavlovian fear conditioning, and signaled avoidance conditioning.
AB  - Neural activity in central and basolateral amygdala nuclei (CeA and BLA,
      respectively) was recorded during delay eyeblink conditioning, Pavlovian fear
      conditioning, and signaled barpress avoidance. During paired training, the CeA
      exhibited robust learning-related excitatory activity during all 3 tasks. By
      contrast, the BLA exhibited minimal activity during eyeblink conditioning, while
      demonstrating pronounced increases in learning-related excitatory responsiveness
      during fear conditioning and barpress avoidance. In addition, the relative amount
      of amygdalar activation observed appeared to be related to the relative intensity
      of the unconditioned stimulus and somatic requirements of the task. Results
      suggest the CeA mediates the Pavlovian association between sensory stimuli and
      the BLA mediates the modulation of instrumental responding through the assignment
      of motivational value to the unconditioned stimulus.

PMID- 16300434
TI  - Fear conditioning-induced plasticity in auditory thalamus and cortex: To what
      extent is it expressed during slow-wave sleep?
AB  - After fear conditioning to a tone, rats received nonawakening presentations of
      the tone alone during slow-wave sleep (SWS) episodes. Multiunit activity was
      recorded in the medial part of the medial geniculate (MGm) and in the primary
      auditory cortex (ACx). Although tone-evoked responses were increased in MGm and
      ACx during the 3 conditioning sessions, group data failed to show any significant
      changes during SWS. Nonetheless, the few recordings (5/29) that exhibited the
      strongest conditioned responses during wakefulness expressed enhanced responding
      during SWS. Compared with previous data obtained in MGm during paradoxical sleep,
      associative plastic changes were less easily expressed during SWS. These results
      are discussed with regard to functional changes that occur in the thalamocortical
      system across vigilance states.

PMID- 16300435
TI  - Involvement of the supramammillary nucleus in aversive conditioning.
AB  - Mechanisms for the retention and retrieval of conditioned taste aversions (CTAs)
      have yet to be fully defined. The authors explored relevant subcortical forebrain
      regions by tracking the expression of immediate early genes, c-fos and zif268.
      The supramammillary nucleus (SuM) was activated following both viscerally based
      CTA and somatically based inhibitory avoidance (IA). Excitotoxic lesions of the
      SuM before conditioning caused no disruption of acquisition but accelerated the
      extinction of both the CTA and IA. In contrast, lesions after CTA conditioning
      did not impair retention or retrieval. The present study indicates that the SuM
      is activated by memory-elicited discomfort during retrieval, suggesting that it
      plays a role in resisting the extinction of a long-term aversive memory.

PMID- 16300436
TI  - GluR-A-dependent synaptic plasticity is required for the temporal encoding of
      nonspatial information.
AB  - Four related experiments studied operant performance of mice on differential
      reinforcement of low rates of responding (DRL) paradigms. Experiment 1 showed
      that excitotoxic hippocampal lesions impaired performance of a 10-s DRL schedule
      (DRL-10). Experiments 2 and 3 showed that GluR-A AMPA receptor subunit knockout
      mice, which are deficient in CA3-CA1 long-term potentiation (LTP), were markedly
      impaired at 15 s (DRL-15), but less impaired at DRL-10. Experiment 4 compared DRL
      15 performance in mice from the 2 strains from which the GluR-A colony was
      derived and showed that they did not differ. The results show that GluR-A
      containing AMPA receptors are required for normal performance on hippocampus
      dependent, nonspatial working memory tasks, consistent with a role for GluR-A in
      the temporal encoding (what happened when) of nonspatial information.

PMID- 16300437
TI  - Dissociating the role of the parietal cortex and dorsal hippocampus for spatial
      information processing.
AB  - Dorsal hippocampus, parietal cortex, and control lesioned rats were tested on
      both a metric and topological task. The metric task consisted of 2 different
      objects placed 68 cm apart on a cheese board. After habituation, the objects were
      moved to a separation of 38 cm on Day 1 and to a separation of 98 cm on Day 2.
      The topological task consisted of 4 different objects placed in a square
      orientation. After habituation, the first 2 objects were switched, and after the
      rats habituated to that change, the back 2 objects were switched. This was
      repeated on a different day with 4 new objects. The data suggest that the
      hippocampus is necessary for metric representations, whereas the parietal cortex
      is necessary for topological representations.

PMID- 16300438
TI  - The influence of hippocampal lesions on the discrimination of structure and on
      spatial memory in pigeons (Columba livia).
AB  - Pigeons (Columba livia) were trained with a spatial structural discrimination,
      which was based on the spatial relationship among the components of a pattern,
      and a feature-binding structural discrimination, which was based on how different
      visual features within a pattern were combined. Neither discrimination was
      impaired by damage to the hippocampus and area parahippocampalis. The lesions
      impaired performance on a spatial working memory and a spatial reference memory
      task in open field. The results indicate an intact hippocampus is not essential
      for the solution of structural discriminations in pigeons and the hippocampus is
      important for processing some types of spatial information--that used in
      navigation, but not other types--that used in spatial structural discriminations.

PMID- 16300439
TI  - Chlordiazepoxide interactions with scopolamine and dizocilpine: novel cooperative
      and antagonistic effects on spatial learning.
AB  - The authors investigated the effects on spatial behavior of coadministrations of
      a benzodiazepine, chlordiazepoxide (CDP), with a noncompetitive N-methyl-d
      aspartate receptor antagonist (NMDAR), dizocilpine (DZP), and a muscarinic
      cholinergic receptor antagonist, scopolamine (SCP). Rats solved the Morris swim
      task in 2 settings; 1 in which a hidden escape platform was always in the same
      location (performance) and a 2nd in which the platform had been moved to a
      different location (acquisition) for repeated daily sessions. CDP (3.0 mg/kg)
      administered alone did not disrupt escape latencies or swim path accuracies. SCP
      and DZP each impaired acquisition and performance in a dose-dependent manner. CDP
      coadministered with 0.3 mg/kg SCP impaired escape only in the acquisition setting
      and when coadministered with 1.0 mg/kg SCP selectively exacerbated the escape
      impairment in the acquisition setting. CDP ameliorated deleterious effects of DZP
      in both settings.

PMID- 16300440
TI  - Bright light suppresses hyperactivity induced by excitotoxic dorsal hippocampus
      lesions in the rat.
AB  - The hippocampus has been implicated in anxiety, novelty detection, spatial-
      contextual processing, and hyperactivity. Accordingly, the authors contrasted the
      role of the dorsal hippocampus (DH) and the basolateral amygdala complex (BLA) in
      an open field task that presents the onset and termination of a bright light
      gradient. In the dark, DH rats demonstrated impaired habituation of locomotion
      behavior and hyperactivity, whereas in bright light their behaviors were normal.
      DH rats responded differentially to the onset and termination of the light
      stimulus, which indicates they have normal novelty detection. BLA lesion rats
      responded normally to bright light. These results demonstrate that a mild fear
      stimulus, such as bright light, can suppress DH lesion-evoked hyperactivity, and
      this hyperactivity results from impaired contextual processing.

PMID- 16300441
TI  - The human pulvinar and stimulus-driven attentional control.
AB  - The present study compared the behavioral effects of sudden motion onsets or
      color changes (i.e., featural changes) with the effects of new objects (i.e.,
      multiple changes). Experiments 1 and 2 showed that lesions of the pulvinar affect
      stimulus-driven attentional control only when it is triggered by featural
      changes, but not by new objects. Experiment 3 revealed that when appended on a
      new object, a featural change is processed as a part of a more massive new
      object: Its attentional effects are larger and remain undisturbed by lesions of
      the pulvinar. In Experiment 4 a temporal superiority effect was found for
      featural changes, but not for new objects in healthy subjects. These results
      suggest that featural changes and new objects may be processed through different
      pathways and that the pulvinar may be particularly involved in stimulus-driven
      attentional control by sudden events entailing featural changes.

PMID- 16300442
TI  - Nutritional deficits during early development affect hippocampal structure and
      spatial memory later in life.
AB  - Development rates vary among individuals, often as a result of direct competition
      for food. Survival of young might depend on their learning abilities, but it
      remains unclear whether learning abilities are affected by nutrition during
      development. The authors demonstrated that compared with controls, 1-year-old
      Western scrub jays (Aphelocoma californica) that experienced nutritional deficits
      during early posthatching development had smaller hippocampi with fewer neurons
      and performed worse in a cache recovery task and in a spatial version of an
      associative learning task. In contrast, performance of nutritionally deprived
      birds was similar to that of controls in 2 color versions of an associative
      learning task. These findings suggest that nutritional deficits during early
      development have long-term consequences for hippocampal structure and spatial
      memory, which, in turn, are likely to have a strong impact on animals' future
      fitness.

PMID- 16300443
TI  - Neonatal handling alters brain organization but does not influence recovery from
      perinatal cortical injury.
AB  - Handling rat pups by removing them from the nest during the preweaning period has
      been shown to influence brain and behavioral development. The authors
      hypothesized that handling rats with perinatal (Day 4) medial frontal cortex
      removals might attenuate behavioral deficits and reverse dendritic atrophy
      associated with such an injury. On the day after surgery, pups were removed from
      the nest for 15 min, 3 times per day until weaning. Animals were tested as adults
      in the Morris water task and on skilled reaching. Handled animals showed no
      improvement in behavioral performance. The handling procedure led to a decrease
      in dendritic length in parietal cortex, but spine density was unchanged. No
      therapeutic advantage was observed following the preweaning handling of brain
      injured rats.

PMID- 16300444
TI  - Maternally modulated infant separation responses are regulated by D2-family
      dopamine receptors.
AB  - Although dopamine is necessary for mammalian adult pair-bond formation and
      maternal behavior, its function in infant social behavior and attachment has been
      less thoroughly explored. The vocalization rate of an isolated rat pup is
      influenced by recent social contact. Interactions with the dam potentiate
      vocalization rate. Interactions with littermates or adult males do not. Systemic
      administration of the D2-family agonist quinpirole specifically blocked maternal
      potentiation at doses that did not alter vocalization rate in an isolation prior
      to dam contact. This result was not explained by quinpirole's effects on body
      temperature or locomotion. The results are consistent with a role for dopamine in
      infant social behavior.

PMID- 16300445
TI  - Memory impairment in obese Zucker rats: an investigation of cognitive function in
      an animal model of insulin resistance and obesity.
AB  - The genetically obese Zucker rat is a widely investigated model of pathological
      changes associated with type 2 diabetes. To assess cognitive function, obese and
      lean Zucker rats were tested on a variable-interval delayed alternation test of
      learning and memory. There were no group differences in learning the alternation
      rule or at short intervals, but obese rats were impaired at longer intervals
      where performance is hippocampus dependent. Plasma membrane association of the
      insulin sensitive glucose transporter, GLUT4, was reduced in the hippocampus of
      obese rats in the absence of changes in total GLUT4 and insulin receptor
      expression. These results parallel those of human studies in pointing to the
      susceptibility of the hippocampus and related structures to the adverse
      environment of diabetes mellitus.

PMID- 16300446
TI  - Dorsal hippocampus involvement in trace fear conditioning with long, but not
      short, trace intervals in mice.
AB  - Placing a "trace" interval between a warning signal and an aversive shock makes
      consolidation of the memory for trace conditioning hippocampus dependent. To
      determine the trace at which memory consolidation requires the hippocampus, mice
      were trained with 0-s, 1-s, 3-s, or 20-s trace intervals and tested for freezing
      to context and tone. Posttraining dorsal hippocampus (DH) lesions decreased
      context conditioning regardless of trace interval. However, DH lesions attenuated
      only the 20-s trace tone freezing. Like eyeblink conditioning, the DH is
      necessary for trace fear conditioning only at long trace intervals, but the time
      scale for the effective interval in fear conditioning is about 40 times longer.
      Manipulations that alter trace fear conditioning with short trace intervals
      probably do not reflect altered DH function. Given this difference in time scale
      along with the use of posttraining DH lesions, hippocampus dependency of trace
      conditioning is not related to a bridging function or response timing.

PMID- 16300447
TI  - A near hat trick for Harlow (1953) with further thoughts on drive: theoretical
      comment on Barbano and Cador (2005).

PMID- 16300448
TI  - Central and basolateral amygdala neurons crash the aversive conditioning party:
      Theoretical comment on Rorick-Kehn and Steinmetz (2005).

PMID- 16300449
TI  - The value of a comparative perspective: theoretical comment on Pearce et al.
      (2005).

PMID- 16300450
TI  - Adaptive priorities in brain development: theoretical comment on Pravosudov et
      al. (2005).

PMID- 16300451
TI  - Withdrawal.

PMID- 16300452
TI  - Hypertension in America: a national reading.
AB  - The prevalence of hypertension in the United States is increasing despite
      increased awareness of the importance of controlling blood pressure (BP). The
      growing prevalence of obesity is a major factor in the increased prevalence of
      hypertension; the aging of the population is another factor. Age, weight, and
      ethnicity are strong predictors of hypertension. Blacks, older individuals, and
      people with diabetes have the highest rates. Although Healthy People 2010 has
      established a target of 50% for hypertension control, the most recent National
      Health and Nutrition Examination Survey indicates that only about 30% of
      individuals with hypertension have their BP controlled. Several barriers to
      effective BP control have been identified, including patient access and adherence
      to therapy and provider failure to initiate or intensify therapy.

PMID- 16300453
TI  - Update on the efficacy of angiotensin receptor blockers in treatment of
      hypertension.
AB  - Angiotensin II, the principal effector peptide of the renin-angiotensin
      aldosterone system (RAAS), has potent vasoconstrictive and other effects that can
      lead to cardiac and renal complications. Angiotensin receptor blockers (ARBs),
      which block the effects of angiotensin II at the receptor level, antagonize
      angiotensin II's vasoconstrictive and prooxidant effects, decrease aldosterone
      secretion, and mitigate sympathetic activity. The antihypertensive efficacy of
      the ARBs has been demonstrated in large clinical trials. In addition to their
      blood pressure-lowering effect, these agents also provide cardiovascular (CV)
      protection and reduce CV mortality as effectively as other classes of
      antihypertensive agents. By inhibiting the RAAS, the ARBs also have
      renoprotective effects and are indicated for the treatment of hypertension in
      patients with diabetes. They have also been shown to lower the incidence of new
      onset diabetes in high-risk hypertensive patients. Combining ARBs with other
      antihypertensive drugs increases their antihypertensive efficacy.

PMID- 16300454
TI  - Tolerability and quality of life in ARB-treated patients.
AB  - Side effects associated with some antihypertensive agents can adversely affect
      patient adherence to a treatment regimen. Controlled clinical trials involving
      >11,000 patients have consistently shown that the angiotensin receptor blockers
      (ARBs) are generally well tolerated. Adverse effects, such as headache,
      lightheadedness, dizziness, nausea, and diarrhea, have been described as mild to
      moderate. The frequency of cough is significantly lower in patients treated with
      ARBs than in those receiving angiotensin-converting enzyme inhibitors (ACEIs).
      Angioedema, a less common but more serious side effect, also appears to be seen
      less frequent with ARBs than with ACEIs, although cross-reactivity is possible.
      Quality of life (QOL) is another important factor affecting treatment adherence.
      Recent studies have shown improvements in QOL measures in patients switched from
      other classes of antihypertensive agents to ARBs.

PMID- 16300455
TI  - After the diagnosis: adherence and persistence with hypertension therapy.
AB  - Poor adherence to therapy is a major reason that large percentage of patients
      with hypertension fail to achieve good blood pressure control. Side effects, such
      as cough, dizziness, nausea, and headache, are frequently cited as reasons for
      lack of adherence and persistence with hypertension therapy. Use of newer classes
      of antihypertensive agents with better tolerability than older agents may be one
      way to improve adherence and persistence. Recent studies have shown higher rates
      of adherence and persistence with therapy in patients treated with angiotensin
      receptor blockers, angiotensin-converting enzyme inhibitors, or newer calcium
      channel blockers compared with other antihypertensive agents. Health insurance
      coverage can also affect patient adherence and persistence.

PMID- 16300456
TI  - Angiotensin receptor blockers: impact on costs of care.
AB  - Direct and indirect costs related to the treatment of hypertension are estimated
      at nearly $60 billion annually. Short- and long-term costs of healthcare
      utilization and treatment are, therefore, important considerations in selection
      of antihypertensive therapy. Studies of patients with hypertension and type 2
      diabetes have shown that treatment with angiotensin receptor blockers (ARBs) can
      reduce healthcare costs as a result of a decreased incidence of end-stage renal
      disease and other clinical end points. ARBs also increase survival in these
      patients. Cost savings have also been reported in patients with heart failure as
      a result of reductions in office and emergency department visits, hospital
      admissions, and hospital stays.

PMID- 16300457
TI  - Epidemiology of hyperuricemia and gout.
AB  - Gout is an increasingly common medical problem. The traditional risk factors of
      male sex and high red meat or alcohol consumption have been joined by a wave of
      newer risk factors, such as increased longevity, the metabolic syndrome
      (hypertension, diabetes, dyslipidemia, truncal obesity, increased cardiovascular
      disease risk), use of diuretics, low-dose aspirin, or cyclosporine, and end-stage
      renal disease. Atypical presentations of gout in the elderly can mimic
      osteoarthritis and rheumatoid arthritis. There is a resurgence of interest in
      hyperuricemia as an independent and potentially modifiable cardiovascular risk
      factor. The pharmacologic management of gout in general practice suffers from a
      number of quality-control issues. This article reviews these and other new
      epidemiologic data on this ancient disease.

PMID- 16300458
TI  - Diagnosis of gout: clinical, laboratory, and radiologic findings.
AB  - Acute gouty arthritis typically presents with a sudden and severe exquisitely
      painful joint, most classically in the first metatarsophalangeal joint (toe).
      Demonstrating the presence of monosodium urate (MSU) crystals in the joint fluid
      or tophus has been the gold standard for the diagnosis of gout. However, many
      physicians do not perform synovial fluid analysis. In the absence of
      demonstrating the presence of MSU crystals in aspirated joint fluid or tophus,
      clinical, radiologic, and laboratory criteria are helpful. This article presents
      an overview of the various classification criteria, clinical presentations, and
      laboratory and radiologic studies needed to make the diagnosis of gout.

PMID- 16300459
TI  - Understanding treatments for gout.
AB  - Gout is one of the most readily manageable of the rheumatic diseases. This
      article reviews basic pathways in purine metabolism, uric acid handling, and the
      pathogenic mechanism of clinical gout, as well as the areas in those pathways
      amenable to intervention. Attention is also given to associated comorbidities,
      such as hyperuricemia and obesity, hypertension, hyperinsulinemia, and coronary
      artery disease. The significance of lifestyle modifications, such as weight loss
      and alcohol reduction, is discussed as an important adjunct to pharmacotherapy in
      gout. Current and investigational agents used in gout management are also
      reviewed. Finally, treatment recommendations for acute and chronic gout are
      suggested.

PMID- 16300460
TI  - Clinical, humanistic, and economic outcomes of gout.
AB  - Gout is a low prevalence disease not often considered by managed care
      organizations with regard to cost management. Understanding the development of
      the disease and its potential long-term, high-cost consequences can lead to
      appropriate treatment strategies and cost-management opportunities that can
      improve patient outcomes and potentially lower the overall cost of treatment of
      patients with gout in a managed care organization. The acute and chronic nature
      of the disease is best managed up front to avoid negative long-term effects.
      Adherence to medications can also impact the manifestation of the disease.

PMID- 16300461
TI  - Evaluation and treatment of asthma: an overview.
AB  - The delivery of optimal care to individuals with bronchial asthma remains a
      challenge to practicing physicians. Asthma is a chronic, inflammatory condition
      that requires diligent long-term follow-up. This article will address the
      diagnostic evaluation of patients with asthma and present an overview of drugs
      commonly used in treatment.

PMID- 16300462
TI  - Aligning patient care and asthma treatment guidelines.
AB  - This article describes how the National Asthma Education and Prevention Program
      Guidelines for the Diagnosis and Management of Asthma can be used in the clinical
      setting to improve a patient's everyday function and quality of life. Major
      recommendations are detailed and case studies provide a practical approach for
      patient management.

PMID- 16300463
TI  - Asthma treatment guidelines: how do we measure up?
AB  - The use of clinical guidelines for the management of asthma can help improve
      patient outcomes and control costs. This article explores ways that managed care
      organizations can encourage physicians to follow guidelines more consistently to
      achieve better asthma management outcomes among their patients and reduce
      healthcare spending.

PMID- 16300464
TI  - Targeting histone deacetylase 2 in chronic obstructive pulmonary disease
      treatment.
AB  - There is increasing evidence that histone acetylation plays a critical role in
      the regulation of inflammatory genes and in mediating the anti-inflammatory
      effects of corticosteroids. Inflammatory stimuli through transcription factors,
      such as NF-kappaB, recruit co-activator molecules with intrinsic histone
      acetyltransferase activity, leading to hyperacetylation of core histones and gene
      activation. Histone deacetylases (HDACs) reverse this process and suppress
      inflammatory genes. Corticosteroids, the most effective anti-inflammatory drugs
      so far available, recruit HDAC2 to activated inflammatory gene complexes through
      an interaction with glucocorticoid receptor and thus switch off activated
      inflammatory genes. In chronic obstructive pulmonary disease and in asthmatic
      patients who smoke, there is a reduction in HDAC2 activity and expression,
      resulting in amplification of inflammation and corticosteroid resistance.
      Therapeutic strategies to increase HDAC activity may, therefore, be expected to
      reduce inflammation and restore steroid responsiveness. These strategies include
      low doses of theophylline or antioxidants and nitric oxide synthase inhibitors.
      HDACs may be inhibited directly by siRNA and in the future by small-molecule
      activators may be discovered through high output screening. These drugs may
      represent a novel approach to treating chronic inflammatory diseases.

PMID- 16300465
TI  - IL-23: changing the verdict on IL-12 function in inflammation and autoimmunity.
AB  - IL-12 and IL-23 are molecules mainly produced by activated accessory and antigen
      presenting cells. The tools for studying the biology of IL-12 in man and
      laboratory rodents have greatly advanced our appreciation of the central role of
      this molecule in cell-mediated immunity and inflammation. In particular, IL-12 is
      thought to be the prime-regulator of TH1 development. Targeting what was thought
      to be IL-12 function in vivo, resulted in drastic amelioration of inflammation
      and autoimmunity firmly linking TH1 polarisation to autoimmune development. Upon
      discovery of IL-23 and the fact that the large subunit of IL-23 is shared by IL
      12, the research community only begins to grasp that the features attributed to
      IL-12 and TH1 development in inflammation are, in fact, dependent on IL-23 and
      not on IL-12. Hence, the perception of IL-12 biology is, to a large extent, based
      on a mistaken identity. In this review, the authors provide an overview of their
      current understanding of IL-12 and IL-23 biology in inflammation and
      autoimmunity, and how this viewpoint has been readjusted over the past 15 years.

PMID- 16300466
TI  - Hedgehog and spinal cord injury.
AB  - The hedgehog (Hh) pathway is a highly conserved signalling cascade involved in
      many developmental processes, including a key role in morphogenesis of many
      tissues including the limb bud, lung, gut, hair follicle and the neural tube. Hh
      role in adult tissue is less well-established, however, it is known that the
      pathway becomes activated and reutilised in situations of repair and
      regeneration. In the nervous system, tissue repair appears impeded in that mature
      neurons undergo their final cell divisions early in life and central axons do not
      easily regenerate. The Hh pathway has been shown to be activated in response to
      nerve damage, leading to the hypothesis that enhancing Hh pathway activation in
      damaged nerve tissue, inducing the repair process, could offer a potentially new
      approach to treating neurodegenerative diseases and dysfunction, including spinal
      cord injury.

PMID- 16300467
TI  - Recent advances in targeted therapy of human myelogenous leukaemia.
AB  - Despite major advances in the diagnosis and treatment of myelogenous leukaemia
      during the past few decades, this group of diseases remains a serious medical
      concern with > 15,000 new cases each year and a mortality rate of approximately
      10,000 in the US alone. Current available conventional therapies, including
      chemotherapy and bone marrow transplantation, often cause severe side effects
      owing mainly to the lack of specificity of the treatment. In the past years,
      significant progress has been made towards understanding the pathogenesis of
      myelogenous leukaemia from the molecular standpoint. To this end, a growing
      number of approaches are being exploited for the identification and validation of
      new therapeutic targets suitable for more potent and specific or 'targeted'
      intervention. In this review, the authors focus their discussion on the four most
      promising myelogenous leukaemia-associated molecular targets currently being
      pursued by major pharmaceutical and biotechnology companies, fms-like tyrosine
      kinase 3 (FLT3), CD33, farnesyl transferase and BCR-Abl, with emphasis on recent
      progress on the clinical development of therapeutic agents, including both kinase
      inhibitors and monoclonal antibodies, to these targets.

PMID- 16300468
TI  - Functional and prognostic role of ZAP-70 in chronic lymphocytic leukaemia.
AB  - It has become clear that the heterogeneity of chronic lymphocytic leukaemia (CLL)
      is not a continuous spectrum, but is bipolar. Originally distinguished by the
      mutational status of the immunoglobulin variable region genes, the two poles are
      perhaps better identified by the expression of ZAP-70, a signalling molecule
      normally utilised by T cells rather than B cells, but anomalously expressed in
      the more aggressive subtype of CLL. Assaying ZAP-70 expression has become
      progressively simplified so that a directly stained flow cytometric test is
      currently being evaluated, and a version of this should shortly be available to
      routine laboratories. In addition, the understanding of the nature of CLL has
      been advanced rapidly and this should lead to new, better targeted therapies,
      which in contrast to the current armoury, will work better for the more malignant
      variants of CLL than for the more benign. In particular, ZAP-70 is especially
      attractive because its aberrant expression in tumour cells from the more
      aggressive forms of CLL requires the chaperoning action of activated heat-shock
      protein 90, which may be specifically inhibited.

PMID- 16300469
TI  - EphA2 as a target for ovarian cancer therapy.
AB  - EphA2 is a receptor tyrosine kinase that is overexpressed by many human cancers,
      and is often associated with poor prognostic features. It is involved in many
      processes crucial to malignant progression, such as migration, invasion,
      metastasis, proliferation, survival and angiogenesis. Inducing EphA2
      downregulation by any one of several mechanisms (antibody-mediated inhibition of
      signalling, antibody-mediated downregulation of total EphA2 expression and siRNA
      mediated inhibition of expression) has been shown to decrease tumour growth,
      prolong survival and inhibit angiogenesis in multiple preclinical models of
      ovarian, breast and pancreatic cancer. Targeting EphA2 is especially attractive
      in ovarian cancer, in which overexpression is present in > 75% of cases. This
      disease is highly responsive to chemotherapy, and EphA2 inhibition is especially
      effective in combination with taxanes. This demonstrated efficacy, along with the
      low expression of EphA2 by normal adult tissues and lack of demonstrable
      toxicities in preclinical models, suggest that long-term treatment with EphA2
      targeting agents is an attractive approach for ovarian cancer therapy.

PMID- 16300470
TI  - Individualised cancer therapeutics: dream or reality?
AB  - Traditional measures for treating metastatic cancer involve identification of the
      originating organ from which the neoplasm arose and empirical treatment with
      cytotoxic chemotherapy. Arguably, with the exception of haematological
      malignancies, demonstration of efficacy in solid tumours has been limited. Over
      the past half-decade, theoretical and technological advances have resulted in
      greater application of molecular science to drug design, which has enabled
      development of new 'targeted' therapeutics. However, generic chemotherapy
      paradigms have not changed. Establishment of the optimal population for
      'targeted' therapeutics based on molecular diagnostics (i.e. genomic and
      proteomic characterisation) to identify sensitive tumour-host ecosystems in
      individual patients at the 'bedside', is not being done as part of routine
      oncology management. This review focuses on the concept of designing
      individualised therapeutics based on genomic and proteomic profile of malignant
      tissue. Genetic and epigenetic perturbations in signal pathways drive cancer
      growth, survival, invasion and metastatic spread. The burgeoning evidence which
      supports the concept that each patient's cancer has a unique complement of
      pathogenic genetic and molecular derangements is reviewed. Such evidence supports
      the strategy of individualised selection of a therapeutic complex from a menu of
      targeting options that best complements the specific oncomolecular profile of the
      'tumour-host' system.

PMID- 16300471
TI  - Targeting Ubc9 for cancer therapy.
AB  - Ubiquitin-conjugating enzyme (Ubc9) was originally thought to be a conjugating
      enzyme for ubiquitylation, but was later shown to be responsible for the most
      recently identified type of post-translational modification, (i.e., SUMO [small
      ubiquitin-related modifier]) conjugation or sumoylation. Like ubiquitylation,
      sumoylation modulates protein function through post-translational covalent
      attachment to lysine residues within targeted proteins. However, although
      ubiquitylation can lead to protein degradation through the 26S proteasome,
      sumoylation does not cause protein degradation; instead, it has been implicated
      in other cellular processes, such as regulating the activity of transcription
      factors, mediating nuclear translocation of proteins or the formation of
      subnuclear structures. Interestingly, some proteins can be modified at the same
      lysine residue by both SUMO and ubiquitin, but with distinct functional
      consequences. Given that many proteins involved in cell-cycle regulation,
      proliferation, apoptosis and DNA repair are targets for sumoylation, alterations
      of sumoylation could ultimately have an impact on cell growth, cancer development
      and drug responsiveness. As Ubc9 is the sole E2-conjugating enzyme required for
      sumoylation, and, in particular, Ubc9 is upregulated in an increasing number of
      human malignancies, such as ovarian carcinoma, melanoma and lung adenocarcinoma,
      it is a potential target for cancer therapy.

PMID- 16300472
TI  - Exploring the tumour environment: cancer-associated fibroblasts as targets in
      cancer therapy.
AB  - Stroma cells contribute to the microenvironment that is essential for cancer
      growth, invasion and metastatic progression. Fibroblasts, often termed
      myofibroblasts or cancer-associated fibroblasts (CAFs), represent the most
      abundant cell type in the tumour stroma. The demonstrated tumour-promoting
      capacities of CAFs has increased the interest to exploit them as drug targets for
      anticancer therapy. Although single factors, such as platelet-derived growth
      factor, transforming growth factor-beta1, hepatocyte growth factor and matrix
      metalloproteinases have been identified as mediators in the fibroblast tumour
      interaction, the morphological and functional differences of CAFs compared with
      their normal counterparts are only incompletely understood. Recently, novel
      global methods for gene expression profiling were applied to comprehensively
      characterise CAFs from breast, pancreas, colon and basal cell cancer in their in
      situ environment. The analysis of different CAF preparations revealed regulated
      genes that were previously not described in the tumour-stroma context.
      Additionally, besides a few striking overlaps, the comparison of the gene lists
      indicates a high level of heterogeneity in the expression pattern of CAFs from
      different tumour types. Together, these studies emphasise the importance of cross
      talk between stromal and malignant cells of the tumour. It is likely that the
      continued characterisation of this interaction, and the molecular identification
      of key mediators, will provide insights into tumour biology and suggest novel
      therapeutic options.

PMID- 16300473
TI  - Antibody-based antiangiogenic cancer therapy.
AB  - Monoclonal antibodies are beginning to fulfil their potential as therapeutics in
      different pathological conditions, with a special focus on cancer. At the same
      time, antiangiogenic therapy has evolved into one of the most active fields in
      cancer research. The logical combination of both strategies has produced a
      growing number of antibodies aimed to interfere with tumour angiogenesis at
      different steps of the angiogenic process. This development has taken advantage
      of recombinant technologies that have revolutionised the selection and production
      of monoclonal antibodies, and gene therapy approaches that achieve sustained and
      effective concentrations of therapeutic antibodies in vivo. Here, the current
      knowledge about these antibody-based antiangiogenic strategies is summarised and
      the authors propose a novel therapeutic approach based on the blocking of crucial
      binding sites present in the extracellular matrix.

PMID- 16300474
TI  - Genetic variation in G-protein-coupled receptors--consequences for G-protein
      coupled receptors as drug targets.
AB  - G-protein-coupled receptors (GPCRs), including 'orphan' GPCRs whose natural
      ligands are unknown, comprise the largest membrane receptor superfamily and are
      the most commonly used therapeutic targets. GPCR genetic loci harbour numerous
      variants, such as DNA insertions or deletions and single nucleotide polymorphisms
      that alter GPCR expression and function, thereby contributing to inter-individual
      differences in disease susceptibility/progression and drug responses. In this
      article, the authors review examples of GPCR genetic variants that influence
      transcription, translation, receptor folding and expression on cell surface (by
      affecting receptor trafficking, dimerisation, desensitisation/downregulation), or
      perturb receptor function (by altering ligand binding, G-protein coupling and
      receptor constitutive activity). In spite of such effects, assessment for genetic
      variants is not currently applied to the drug development and approval process or
      in the clinical use of GPCR drugs. Further insights will, the authors believe,
      alter drug discovery/development, therapeutics and likely provide new GPCR drug
      targets.

PMID- 16300475
TI  - The therapeutic potential of CXCR4 antagonists in the treatment of HIV infection,
      cancer metastasis and rheumatoid arthritis.
AB  - CXCR4 is the receptor of the chemokine CXCL12, which is involved in progression
      and metastasis of several types of cancer cells, HIV infection and rheumatoid
      arthritis. The authors developed selective CXCR4 antagonists, T22 and T140,
      initially as anti-HIV agents, which inhibit T cell line-tropic (X4-) HIV-1
      infection through their specific binding to CXCR4. Recently, T140 analogues have
      also been shown to inhibit CXCL12-induced migration of breast cancer cells,
      leukaemia T cells, pancreatic cancer cells, small cell lung cancer cells, chronic
      lymphocytic leukaemia B cells, pre-B acute lymphoblastic leukaemia cells and so
      on in vitro. Biostable T140 analogues significantly suppressed pulmonary
      metastasis of breast cancer cells and melanoma cells in mice. Furthermore, these
      compounds significantly suppressed the delayed-type hypersensitivity response
      induced by sheep red blood cells and collagen-induced arthritis, which represent
      in vivo mouse models of arthritis. Thus, T140 analogues proved to be attractive
      lead compounds for chemotherapy of these problematic diseases. This article
      reviews recent research on T140 analogues, referring to several other CXCR4
      antagonists.

PMID- 16300476
TI  - Phosphodiesterase-4 as a potential drug target.
AB  - Phosphodiesterase-4 (PDE4) is the predominant enzyme in some specific cell types
      that is responsible for the degradation of the second messenger, cAMP.
      Consequently, PDE4 plays a crucial role in cell signalling and, as such, it has
      been the target of clinical drug development of various indications, ranging from
      anti-inflammation to memory enhancement. In this review, the fundamental
      biological role of PDE4 in intracellular signalling, its tissue distribution and
      regulation are described. The historical development of various chemical classes
      of PDE4 inhibitors and the challenges that face these inhibitors as therapeutics
      are also discussed. Finally, recent advances in the structural biology of PDE4
      and their complexes with various inhibitors, as well as its potential impact on
      the rational design of potent and selective PDE4 inhibitors, are presented.

PMID- 16300477
TI  - Can intervention in inositol phosphate signalling pathways improve therapy for
      cystic fibrosis?
AB  - Airway epithelial cells from cystic fibrosis (CF) individuals cannot secrete
      adequate Cl- through cystic fibrosis transmembrane regulator, and their Na+
      channel (ENaC) activity is increased so that excessive Na+ and water is absorbed
      from the lumen. These aberrant transport activities can, at least partly, be
      compensated by pharmacologically increasing the activities of Ca2+-activated Cl-
      channels (CaCCs). The therapeutic value of this approach is currently being
      examined in clinical trials of candidate CF drugs such as INS-37217 (Inspire
      Pharmaceuticals) and Moli1901 (Lantibio, Inc.). This review argues that these
      drug development programmes will be helped if one can fully understand how the
      CaCCs are inhibited by inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P4), so
      that there can be pharmacological intervention in this process. Furthermore,
      genes that encode enzymes controlling Ins(3,4,5,6)P4 metabolism should be viewed
      as impacting upon CaCC activity; this, in turn, may influence the severity of the
      CF condition. Expression profiling of genes that regulate inositol phosphate
      metabolism may also illuminate variability in patient response to treatment
      regimens that target CaCCs. Compounds have been developed that can activate CaCCs
      by antagonising their inhibition by Ins(3,4,5,6)P4. One member of this drug
      family (INO-4995; Inologic) was recently shown to inhibit ENaC, thereby reducing
      fluid absorbtion by airway epithelial cells.

PMID- 16300478
TI  - Calmodulin kinase II as a target for inhibition in cardiac disease.

PMID- 16300479
TI  - Structural plasticity of the cyclic-cystine-knot framework: implications for
      biological activity and drug design.
AB  - The cyclotide family of plant proteins is of interest because of their unique
      topology, which combines a head-to-tail cyclic backbone with an embedded cystine
      knot, and because their remarkable chemical and biological properties make them
      ideal candidates as grafting templates for biologically active peptide epitopes.
      The present study describes the first steps towards exploiting the cyclotide
      framework by synthesizing and structurally characterizing two grafted analogues
      of the cyclotide kalata B1. The modified peptides have polar or charged residues
      substituted for residues that form part of a surface-exposed hydrophobic patch
      that plays a significant role in the folding and biological activity of kalata
      B1. Both analogues retain the native cyclotide fold, but lack the undesired
      haemolytic activity of their parent molecule, kalata B1. This finding confirms
      the tolerance of the cyclotide framework to residue substitutions and opens up
      possibilities for the substitution of biologically active peptide epitopes into
      the framework.

PMID- 16300480
TI  - Telomere length in white blood cells is not associated with morbidity or
      mortality in the oldest old: a population-based study.
AB  - Cross-sectional studies have repeatedly suggested peripheral blood monocyte
      telomere length as a biomarker of aging. To test this suggestion in a large
      population-based follow-up study of the oldest old, we measured telomere length
      at baseline in 598 participants of the Leiden 85-plus Study (mean age at baseline
      89.8 years). We also obtained second telomere measurements from 81 participants
      after an average time span of between 3.9 and 12.9 years. Telomere length at
      baseline was not predictive for mortality (P > 0.40 for all-cause, cardiovascular
      causes, cancer or infectious diseases, Cox regression for gender-adjusted
      tertiles of telomere length) or for the incidence of dementia (P = 0.78).
      Longitudinally, telomere length was highly unstable in a large fraction of
      participants. We conclude that blood monocyte telomere length is not a predictive
      indicator for age-related morbidity and mortality at ages over 85 years, possibly
      because of a high degree of telomere length instability in this group.

PMID- 16300481
TI  - CXCL12 overexpression and secretion by aging fibroblasts enhance human prostate
      epithelial proliferation in vitro.
AB  - The direct relationship between the aging process and the incidence and
      prevalence of both benign prostatic hyperplasia (BPH) and prostate cancer (PCa)
      implies that certain risk factors associated with the development of both
      diseases increase with the aging process. In particular, both diseases share an
      overly proliferative phenotype, suggesting that mechanisms that normally act to
      suppress cellular proliferation are disrupted or rendered dysfunctional as a
      consequence of the aging process. We propose that one such mechanism involves
      changes in the prostate microenvironment, which 'evolves' during the aging
      process and disrupts paracrine interactions between epithelial and associated
      stromal fibroblasts. We show that stromal fibroblasts isolated from the prostates
      of men 63-81 years of age at the time of surgery express and secrete higher
      levels of the CXCL12 chemokine compared with those isolated from younger men, and
      stimulate CXCR4-mediated signaling pathways that induce cellular proliferation.
      These studies represent an important first step towards a mechanistic elucidation
      of the role of aging in the etiology of benign and malignant prostatic diseases.

PMID- 16300482
TI  - Lifespan extension in hypomorphic daf-2 mutants of Caenorhabditis elegans is
      partially mediated by glutathione transferase CeGSTP2-2.
AB  - Electrophilic stress caused by lipid peroxidation products such as 4
      hydroxynonenal (4-HNE) and/or related compounds may contribute to aging. The
      major mode of 4-HNE metabolism involves glutathione conjugation catalyzed by
      specialized glutathione transferases. We have previously shown that glutathione
      transferase CeGSTP2-2, the product of the Caenorhabditis elegans gst-10 gene, has
      the ability to conjugate 4-HNE, and that its overexpression extends lifespan of
      C. elegans. We now demonstrate that the expression level of CeGSTP2-2 correlates
      highly with lifespan in a series of hypomorphic daf-2 mutants of C. elegans. The
      overexpression of CeGSTP2-2 in daf-2 is abrogated in daf-16; daf-2 mutants,
      indicating that expression of the gst-10 gene is modulated by insulin-like growth
      factor signaling. To determine whether the relationship between CeGSTP2-2 and
      lifespan is causal, we used RNAi to knock down CeGSTP2-2. Treatment with gst-10
      specific dsRNA decreased CeGSTP2-2 protein in wild-type N2 and in daf-2 strains
      to an approximately equal level. The ability to conjugate 4-HNE was similarly
      decreased by RNAi, suggesting that the increment of that activity in daf-2 over
      N2 is due largely to the overexpression of CeGSTP2-2. RNAi-mediated knock-down of
      CeGSTP2-2 led to an increased susceptibility to 4-HNE, paraquat, and heat shock,
      and to a shortening of lifespan by 13% in both N2 and daf-2 strains. These
      results indicate that CeGSTP2-2 significantly contributes to the maintenance of
      the soma, and that this function is augmented in daf-2 mutants concordantly with
      other longevity assurance genes, probably via insulin-like growth factor
      signaling.

PMID- 16300483
TI  - Behavioral, physical, and demographic changes in Drosophila populations through
      dietary restriction.
AB  - Dietary restriction (DR) is a valuable experimental tool for studying the aging
      process. Primary advancement of research in this area has relied on rodent
      models, but attention has recently turned toward Drosophila melanogaster.
      However, little is known about the baseline effects of DR on wild-type Drosophila
      and continued experimentation requires such information. The findings described
      here survey the effects of DR on inbred, wild-type populations of Canton-S fruit
      flies and demonstrate a robust effect of diet on longevity. Over a circumscribed
      range of dietary conditions, healthy lifespan varies by as much as 121% for wild
      type Drosophila females. Significant differences are also observed for male
      flies, but the magnitude of the DR effect is less robust. Mortality analyses of
      the survivorship data reveal that this variation in lifespan can be attributed to
      a modulation of the rate parameter for the mortality function - a change in the
      demographic rate of aging. Since the feeding of fruit flies is less easily
      controlled than that of rodents, this research also addresses the validity of
      applying a DR model to Drosophila populations. Feeding and body weight data for
      flies given the various dietary conditions surveyed indicate that Drosophila on
      higher-calorie diets consume a similar volume of food to those on a low-calorie
      diet, resulting in different levels of calorie intake. Fertility and activity
      levels demonstrate that the diets surveyed are comparable, and that increasing
      the calorie content of laboratory food up to twice the normal concentration is
      not pathologic for experimental fly populations.

PMID- 16300484
TI  - Raised cortisol:DHEAS ratios in the elderly after injury: potential impact upon
      neutrophil function and immunity.
AB  - The detrimental effect of stress on the immune response increases with age,
      though the mechanisms responsible are not fully understood. The physiological
      response to stress is regulated in part by the adrenocortical system. Adrenal
      hormones dehydroepiandrosterone sulphate (DHEAS) and cortisol have opposing
      effects on the innate immune system, DHEAS enhances while cortisol suppresses
      immunity and the molar ratio of cortisol to DHEAS increases with age. We found
      that elderly hip fracture patients produced a robust neutrophilia after injury,
      but circulating neutrophils showed an impaired antibacterial response. We
      therefore proposed that adrenocortical hormones mediate the heightened
      immunosuppression seen in the elderly after injury. We examined neutrophil
      function and adrenocortical hormone levels in elderly (> 65 years) hip fracture
      patients and age-matched healthy controls. Thirteen out of 35 elderly patients
      acquired infections following hip fracture. Neutrophil superoxide production was
      lower in elderly hip fracture patients compared with controls (P < 0.005) and
      lower in patients who acquired infection following injury compared with those who
      did not (P < 0.05). Serum cortisol:DHEAS ratio was higher in elderly hip fracture
      patients (0.56 +/- 0.38) compared with either age-matched controls (0.36 +/-
      0.21; P < 0.05) or young fracture patients (0.087 +/- 0.033; P < 0.0001).
      Moreover, cortisol: DHEAS was increased in elderly patients who succumbed to
      infection compared with those who did not (0.803 +/- 0.42 vs. 0.467 +/- 0.28; P <
      0.02). In vitro cortisol significantly decreased neutrophil superoxide generation
      (P < 0.05) and this was prevented by coincubation with DHEAS. We propose that
      increased cortisol:DHEAS ratios may contribute to reduced immunity following
      physical stress in the elderly.

PMID- 16300485
TI  - Apoptosis resistance of senescent human fibroblasts is correlated with the
      absence of nuclear IGFBP-3.
AB  - Signaling through the insulin/IGF axis plays a major role in determining the rate
      of aging in many species. IGF-binding proteins (IGFBPs) modulate the IGF pathway
      in higher organisms. IGFBP-3 accumulates in conditioned medium of senescent human
      fibroblasts, suggesting that it may contribute to the senescent phenotype. IGFBP
      3 can enhance apoptotic cell death in tumor cells due to its ability to target
      intracellular regulators of apoptosis, including nuclear transcription factors.
      Senescent fibroblasts are highly resistant to apoptosis, suggesting that IGFBP-3
      fails to induce apoptosis in this cell type; however, mechanisms of apoptosis
      resistance in senescent cells are poorly understood. To address this question, we
      studied the production and intracellular localization of IGFBP-3 in senescent
      fibroblasts. Whereas IGFBP-3 is highly overexpressed by senescent fibroblasts,
      IGFBP-3 was not detectable in the nucleus of senescent fibroblasts. In tumor
      cells, IGFBP-3 can be internalized by endocytosis, which is considered as a
      prerequisite for the intracellular functions of IGFBP-3 and probably also for its
      transport to the nucleus; we show here that endocytotic uptake of IGFBP-3 does
      not occur in senescent human fibroblasts. This is correlated with a generally
      decreased endocytotic activity of these cells, as shown with the model substrate
      transferrin. The data are consistent with a model where IGFBP-3 accumulation in
      conditioned medium of senescent fibroblasts contributes to growth arrest of these
      cells, whereas the failure to endocytose IGFBP-3 and the absence of nuclear IGFBP
      3 may contribute to the well-established apoptosis resistance of senescent human
      fibroblasts.

PMID- 16300486
TI  - Aging and p53: getting it straight. A commentary on a recent paper by Gentry and
      Venkatachalam.

PMID- 16300487
TI  - Aging, p53 and the '24 gene mutant': getting it right. A reply to Vijg and Hasty.

PMID- 16300492
TI  - Abstracts of the XXVth Congress of the European Association of Veterinary
      Anatomists (EAVA). July 28-31, 2004. Oslo, Norway.

PMID- 16300627
TI  - F-spondin promotes nerve precursor differentiation.
AB  - Cells in the developing nervous system secrete a large number of proteins that
      regulate the migration and differentiation of their neighbors. It is shown here
      that a clonal central nervous system cell line secretes a protein that causes
      both a rat hippocampal progenitor cell line and primary cortical neural cells to
      differentiate into cells with the morphological and biochemical features of
      neurons. This protein was identified as F-spondin. Analysis of F-spondin isoforms
      secreted from transfected cells shows that the core protein without the
      thrombospondin type 1 repeats is sufficient to promote neuronal differentiation
      when adsorbed to a surface. F-spondin can also inhibit neurite outgrowth while
      allowing the expression of nerve-specific proteins when present in a soluble form
      at high concentrations. Therefore, F-spondin can alter cell differentiation in
      multiple ways, depending upon its concentration and distribution between
      substrate-attached and soluble forms.

PMID- 16300628
TI  - Evidence that serotonin reuptake modulators increase the density of serotonin
      innervation in the forebrain.
AB  - The mechanism of action of commonly used antidepressants remains an issue of
      debate. In the experiments reported here we studied the effects of three
      representative compounds, the selective serotonin reuptake inhibitor fluoxetine,
      the selective serotonin reuptake enhancer tianeptine and the selective
      norepinephrine reuptake inhibitor desipramine on the structure of central
      serotonin pathways after a 4-week administration. We found that the serotonin
      modulators fluoxetine and tianeptine, but not desipramine, increase the density
      of 5-HT and serotonin transporter (SERT)-immunoreactive axons in the neocortical
      layer IV and certain forebrain limbic areas, such as piriform cortex and the
      shell region of nucleus accumbens. These changes were noted in the absence of a
      significant effect of serotonin antidepressants on the expression of tryptophan
      hydroxylase (TPH-2), i.e. the rate-limiting enzyme for 5-HT biosynthesis and of
      SERT at the mRNA level. In addition, we found that anterogradely filled terminal
      axons from injections of biotinylated dextran amine into the dorsal raphe showed
      significantly more branching in animals treated with fluoxetine compared with
      animals treated with liposyn vehicle. Our findings suggest that antidepressants
      may exert very selective structural effects on their cognate monoamine systems in
      normal animals and raise the possibility that neurotrophic mechanisms may play a
      role in their clinical efficacy.

PMID- 16300629
TI  - Neurochemical characterization of the release and uptake of dopamine in ventral
      tegmental area and serotonin in substantia nigra of the mouse.
AB  - In the present report, fast-scan cyclic voltammetry was used to identify the
      monoamines that were released by electrical stimulation in mouse brain slices
      containing ventral tegmental area (VTA), substantia nigra (SN) -pars compacta
      (SNc) and -pars reticulata (SNr). We showed that voltammograms obtained in mouse
      VTA were consistent with detection of a catecholamine, while those in both
      subregions of the SN were consistent with detection of an indolamine, based on
      the reduction peak potentials. We used pharmacological blockade and genetic
      deletion of monoamine transporters to further confirm the identity of released
      monoamines in mouse midbrain and to assess the control of monoamines by their
      transporters in each brain region. Inhibition of dopamine and norepinephrine
      transporters by nomifensine (1 and 10 microm) decreased uptake rates in the VTA,
      but did not change uptake rates in either subregion of the SN. Serotonin
      transporter inhibition by fluoxetine (10 microm) decreased uptake rates in the
      SNc and SNr, but was without effect in the VTA. Selective inhibition of the
      norepinephrine transporter by desipramine (10 microm) had no effect in any brain
      region. Using dopamine transporter- and serotonin transporter-knockout mice, we
      found decreased uptake rates in VTA and SN subregions, respectively. Peak signals
      recorded in each midbrain region were pulse number dependent and exhibited
      limited frequency dependence. Thus, dopamine is predominately detected by
      voltammetry in mouse VTA, while serotonin is predominately detected in mouse SNc
      and SNr. Furthermore, active uptake occurs in these areas and can be altered only
      by specific uptake inhibitors, suggesting a lack of heterologous uptake. In
      addition, somatodendritic dopamine release in VTA was not mediated by monoamine
      transporters. This work offers an initial characterization of voltammetric
      signals in the midbrain of the mouse and provides insight into the regulation of
      monoamine neurotransmission in these areas.

PMID- 16300630
TI  - Inhibitors of Rho-kinase modulate amyloid-beta (Abeta) secretion but lack
      selectivity for Abeta42.
AB  - Certain non-steroidal anti-inflammatory drugs (NSAIDs) preferentially inhibit
      production of the amyloidogenic Abeta42 peptide, presumably by direct modulation
      of gamma-secretase activity. A recent report indicated that NSAIDs could reduce
      Abeta42 by inhibition of the small GTPase Rho, and a single inhibitor of Rho
      kinase (ROCK) mimicked the effects of Abeta42-lowering NSAIDs. To investigate
      whether Abeta42 reduction is a common property of ROCK inhibitors, we tested
      commercially available compounds in cell lines that were previously used to
      demonstrate the Abeta42-lowering activity of NSAIDs. Surprisingly, we found that
      two ROCK inhibitors reduced total Abeta secretion in a dose-dependent manner but
      showed no selectivity for Abeta42. In addition, ROCK inhibitors did not increase
      Abeta38 secretion in cell-based assays or reduce Abeta production in gamma
      secretase in vitro assays, which are critical characteristics of Abeta42-lowering
      NSAIDs. The reduction in total Abeta levels by ROCK inhibitors was not
      accompanied by overall-changes in amyloid precursor protein processing. Targeting
      ROCK by expression of dominant-negative or constitutively active ROCK mutants
      failed to modulate Abeta secretion, indicating that ROCK inhibition may either be
      redundant or insufficient for Abeta reduction by ROCK inhibitors. Taken together,
      these results seem to exclude a mechanistic involvement of ROCK in the Abeta42
      lowering activity of NSAIDs.

PMID- 16300631
TI  - Transient changes in nucleus accumbens amino acid concentrations correlate with
      individual responsivity to the predator fox odor 2,5-dihydro-2,4,5
      trimethylthiazoline.
AB  - Predator odors elicit fear and defensive behavioral responses in rats, but a wide
      range of individual responsivity exists. The aim of this study was to examine
      whether individual differences in behavioral responsivity correlate with
      differences in amino acid neurotransmission to a predator fox odor, 2,5-dihydro
      2,4,5-trimethylthiazoline (TMT). We investigated the time course of behaviorally
      evoked amino acid neurotransmitter changes in the nucleus accumbens using on-line
      microdialysis coupled to capillary electrophoresis with 14-s temporal resolution.
      One subset of animals (high responders) showed a large, biphasic increase in
      amino acids, such as glutamate and GABA, which lasted about 3 min. These
      neurochemical changes were highly correlated with increases in locomotion and
      burrowing, but lagged behind the behavioral changes by 2 min. A second subset of
      rats (low responders) showed neither behavioral activation nor changes in amino
      acid neurotransmission. As a positive control, rats were subjected to tail pinch,
      which evoked transient changes in amino acids in all animals. Cocaine (2 mg/kg,
      i.v.) increased locomotion but not amino acid levels. This work demonstrates that
      rapid and transient increases in amino acid neurotransmitters correlate with
      behavioral reactivity to salient stimuli.

PMID- 16300632
TI  - Analysis of transmembrane domain mutants is consistent with sequential cleavage
      of Notch by gamma-secretase.
AB  - gamma-Secretase is a lipid-embedded, intramembrane-cleaving aspartyl protease
      that cleaves its substrates twice within their transmembrane domains (TMD): once
      near the cytosolic leaflet (at S3/epsilon) and again in the middle of the TMD (at
      S4/gamma). To address whether this unusual process occurs in two independent or
      interdependent steps, we investigated how mutations at the S3/epsilon site in
      Notch1-based substrates impact proteolysis. We demonstrate that such mutations
      greatly inhibit not only gamma-secretase-mediated cleavage at S3 but also at S4,
      independent of their impact on NICD stability. These results, together with our
      previous observations, suggest that hydrolysis at the center of the Notch
      transmembrane domain (S4/gamma) is dependent on the S3/epsilon cleavage. Notch
      (and perhaps all gamma-secretase substrates) may be cleaved by sequential
      proteolysis starting at S3.

PMID- 16300634
TI  - Neural tube closure depends on nitric oxide synthase activity.
AB  - Neural tube (NT) closure is a multifactorial process that involves yet unresolved
      molecular mechanisms. It had been shown previously that high levels of nitric
      oxide (NO) block the process of NT closure in the chick embryo by inhibiting
      methionine synthase (MS). The MS inhibition and its effect on NT closure could be
      alleviated by folic acid, suggesting the involvement of the folate-methionine
      pathway in the process. Here we test the hypothesis that endogenous nitric oxide
      synthase (NOS) activity regulates the MS activity required in the process of NT
      closure. The experiments described here reveal that NOS activity per se, is
      indeed critical for NT closure in the chick embryo. Inhibition of NOS activity
      with either 2,4-diamino-6-hydroxypyrimidine (DAHP), which blocks biosynthesis of
      the NOS co-factor tetrahydrobiopterin (BH4), or with calmidazolium, which blocks
      calcium-calmodulin binding to NOS, resulted in reduced MS activity and
      consequently ablated NT closure. Addition of BH4 or the calcium ionophore A23187
      restored NOS and MS activities, resulting in NT closure. The results described
      here imply that NOS and MS activities can serve as functional markers in this
      developmental process as they are essential in the process of NT closure.

PMID- 16300633
TI  - NMDA neuroprotection against a phosphatidylinositol-3 kinase inhibitor, LY294002
      by NR2B-mediated suppression of glycogen synthase kinase-3beta-induced apoptosis.
AB  - To identify the intracellular signaling pathways that mediate the pro-survival
      activity of NMDA receptors (NMDARs), we studied effects of exogenous NMDA on
      cultured rat cortical and hippocampal neurons that were treated with a
      phosphatidylinositol-3-kinase (PI3K) inhibitor, LY294002. NMDA at 5 or 10 microm
      protected against LY294002-induced apoptosis, suggesting NMDAR-mediated
      activation of a survival signaling pathway that is PI3K-independent. NR2B
      specific NMDAR blockers antagonized anti-apoptotic effects of NMDA, indicating a
      critical role of NR2B NMDARs in the neuroprotection. NMDA at 10 microm suppressed
      LY294002-induced activation of a pro-apoptotic kinase, glycogen synthase kinase
      3beta (GSK3beta). GSK3beta activation by LY294002 was associated with decreased
      levels of inhibitory GSK3beta phosphorylation at the Ser9 residue. However, NMDA
      did not prevent the LY294002-mediated decline of phospho-Ser9 levels. In
      addition, NMDA inhibited cortical neuron apoptosis induced by the overexpression
      of either wild type (wt) or Ser9Ala mutant form of GSK3beta, suggesting that NMDA
      suppressed GSK3beta in a Ser9-independent manner. Finally, inhibition of NR2B
      NMDARs reduced the NMDA protection against overexpression of GSK3betawt. These
      data indicate that moderate stimulation of NR2B NMDAR protects against inhibition
      of PI3K by a Ser9-independent inhibition of the pro-apoptotic activity of
      GSK3beta. Hence, the activation of NR2B and the Ser9-independent inhibition of
      GSK3beta are two newly identified elements of the signaling network that mediates
      the pro-survival effects of NMDA.

PMID- 16300635
TI  - Docosahexaenoic acid prevents neuronal apoptosis induced by soluble amyloid-beta
      oligomers.
AB  - A growing body of evidence supports the notion that soluble oligomers of amyloid
      beta (Abeta) peptide interact with the neuronal plasma membrane, leading to cell
      injury and inducing death-signalling pathways that could account for the
      increased neurodegeneration occurring in Alzheimer's disease (AD).
      Docosahexaenoic acid (DHA, C22:6, n-3) is an essential polyunsaturated fatty acid
      in the CNS and has been shown in several epidemiological and in vivo studies to
      have protective effects against AD and cognitive alterations. However, the
      molecular mechanisms involved remain unknown. We hypothesized that DHA enrichment
      of plasma membranes could protect neurones from apoptosis induced by soluble
      Abeta oligomers. DHA pre-treatment was observed to significantly increase
      neuronal survival upon Abeta treatment by preventing cytoskeleton perturbations,
      caspase activation and apoptosis, as well as by promoting extracellular signal
      related kinase (ERK)-related survival pathways. These data suggest that DHA
      enrichment probably induces changes in neuronal membrane properties with
      functional outcomes, thereby increasing protection from soluble Abeta oligomers.
      Such neuroprotective effects could be of major interest in the prevention of AD
      and other neurodegenerative diseases.

PMID- 16300638
TI  - Melatonin and 6-hydroxymelatonin protect against iron-induced neurotoxicity.
AB  - Oxidative damage of biological macromolecules is a hallmark of most
      neurodegenerative disorders such as Alzheimer, Parkinson and diffuse Lewy body
      diseases. Another important phenomenon involved in these disorders is the
      alteration of iron homeostasis, with an increase in iron levels. The present
      study investigated whether 6-hydroxymelatonin (6-OHM) can reduce Fe2+-induced
      lipid peroxidation and necrotic cell damage in the rat hippocampus in vivo. It
      was found that 6-OHM administration proved successful in reducing Fe2+-induced
      neurotoxicity in rat hippocampus. This study provides some evidence of the
      neuroprotective effects of 6-OHM.

PMID- 16300636
TI  - Enhanced episodic-like memory and kindling epilepsy in a rat model of tuberous
      sclerosis.
AB  - Tuberous sclerosis complex (TSC) is a common neurological autosomal-dominant
      syndrome caused by mutations in the TSC1 or TSC2 genes. TSC starts in early
      childhood and is characterized by cerebral hamartomas (benign tumours), severe
      epilepsy and cognitive deficits such as mental retardation and autism. The
      hamartomas are characterized by loss of the remaining wild-type TSC allele, and
      clinical data implicate cerebral hamartomas in the generation of epileptic
      seizures, which may play a significant role in the development of mental
      retardation. The TSC2 mutation predicts alterations in mitogen-associated protein
      kinase (MAPK) and, together with the TSC1 mutation, in mammalian target of
      rapamycin (mTOR) signalling pathways. Both pathways are involved in neuronal
      plasticity. We therefore hypothesized that the heterozygous mutation itself,
      besides cerebral hamartomas, contributes to the pathogenesis of cognitive
      deficits and possibly also epilepsy. Here, we show that young adult TSC2+/- rats,
      which are virtually free of cerebral hamartomas, exhibit enhanced episodic-like
      memory and enhanced responses to chemically-induced kindling. The activation of
      cyclic adenosine monophosphate (cAMP) in the hippocampus results in stronger
      induction of phospho-p42-MAPK in TSC2+/- rats than in wild-type animals. Thus,
      the cognitive phenotype and, possibly, epilepsy in TSC patients may result not
      only from the focal hamartomatous lesions but also, from altered neuronal
      plasticity in the heterozygous tissue.

PMID- 16300640
TI  - A presenilin-independent aspartyl protease prefers the gamma-42 site cleavage.
AB  - beta-Amyloid peptides (Abeta40 and Abeta42) are the major constituents of amyloid
      plaques, which are one of the hallmarks of Alzheimer's disease (AD). The Abeta is
      derived from sequential cleavages of amyloid precursor protein (APP) by beta- and
      gamma-secretases. gamma-Secretase consists of at least four proteins where
      presenilins (PS1 and PS2 or PS) are the catalytic subunit involved in the gamma
      site cleavage of APP. Secretion of both Abeta40 and Abeta42 is significantly
      reduced in PS1 knock-out cells and completely abolished in cells deficient for
      both PS1 and PS2. Consequently, both the PS proteins play essential roles in the
      production of the secretory of Abeta from cells. Recent studies in primary
      neurons, however, suggest that PSs are not required for intracellular Abeta42
      accumulation; thus the intracellular Abeta42 appears to be generated in a PS
      independent manner. Here we present the first biochemical evidence indicating
      that Abeta, especially Abeta42, can be generated in the absence of PS based on an
      in vitrogamma-secretase assay employing membranes prepared from PS-deficient
      Blastocyst-derived (BD) cells. This PS-independent gamma-secretase (PSIG)
      activity is sensitive to the changes in pH and displays an optimal activity at pH
      6.0. Pepstatin A is a potent inhibitor for this proteolytic activity with IC50 of
      1.2 nm and 0.4 nm for Abeta40 and Abeta42 generation, respectively. These results
      indicate that these PS-independent gamma-site cleavages are mediated by an
      aspartyl protease. More importantly, the PSIG activity displays a distinct
      preference in mediating the 42-site cleavage over the 40-site cleavage, thereby
      generating Abeta42 as the predominant product.

PMID- 16300639
TI  - c-Jun NH2-terminal kinase mediates interleukin-1beta-induced inhibition of
      lacrimal gland secretion.
AB  - Sjogren's syndrome, an inflammatory disease affecting the lacrimal and salivary
      glands, is the leading cause of aqueous tear-deficient type of dry eye. We
      previously showed that interleukin-1beta (IL-1beta) protein is up regulated in
      the lacrimal gland of a murine model of Sjogren's syndrome and that exogenous
      addition of this cytokine inhibits neurotransmitter release and lacrimal gland
      protein secretion. In the present study we investigated the role of c-Jun NH2
      terminal kinase (JNK) in IL-1beta-mediated inhibition of lacrimal gland secretion
      and tear production. In vitro, IL-1beta induced a time-dependent activation of
      JNK with a maximum 7.5-fold at 30 min. SP600125, a JNK inhibitor, inhibited, in a
      concentration-dependent manner, IL-1beta-induced activation of JNK with a maximum
      of 87% at 10(-4) m. In vivo, IL-1beta stimulated JNK and the expression of the
      inducible isoform of nitric oxide synthase (iNOS). IL-1beta inhibited high KCl
      and adrenergic agonist induced protein secretion by 85% and 66%, respectively.
      SP600125 alleviated the inhibitory effect of IL-1beta on KCl- and agonist-induced
      protein secretion by 79% and 47%, respectively, and completely blocked the
      expression of iNOS. Treatment for 7 days with SP600125 increased tear production
      in a murine model of Sjogren's syndrome dry eye. We conclude that JNK plays a
      pivotal role in IL-1beta-mediated inhibition of lacrimal gland secretion and
      subsequent dry eye.

PMID- 16300641
TI  - In vitro characterization of a gamma-secretase radiotracer in mammalian brain.
AB  - Inhibition of gamma-secretase is a potential therapeutic target for Alzheimer's
      disease (AD). The present studies have characterized the in vitro properties of a
      radiolabeled small molecule gamma-secretase inhibitor, [3H]compound D (Yan et
      al., 2004, J. Neurosci.24, 2942-2952) in mammalian brain. [3H]Compound D was
      shown to bind with nanomolar affinity (Kd = 0.32-1.5 nM) to a single population
      of saturable sites in rat, rhesus and human brain cortex homogenates, the density
      of binding sites ranging from 4 to 7 nM across the species. Competition studies
      with a structurally diverse group of gamma-secretase inhibitors with a wide range
      of binding affinities showed that the binding affinities of these compounds
      correlated well with their ability to inhibit gamma-secretase in vitro.
      Autoradiographic studies showed that the specific binding of [3H]compound D was
      widely distributed throughout adult rat, rhesus and normal human brain. There did
      not appear to be any difference in distribution of [3H]compound D specific
      binding sites in AD cortex compared with control human cortex as measured using
      tissue section autoradiography, nor any correlation between gamma-secretase
      binding and plaque burden as measured immunohistochemically. [3H]compound D is a
      useful tool to probe the expression and pharmacology of gamma-secretase in
      mammalian brain.

PMID- 16300642
TI  - 3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological
      mechanisms underlying striatal degeneration in Huntington's disease.
AB  - Huntington's disease (HD) is a neurodegenerative disorder caused by a mutation in
      the gene encoding Huntingtin. The mechanisms underlying the preferential
      degeneration of the striatum, the most striking neuropathological change in HD,
      are unknown. Of those probably involved, mitochondrial defects might play an
      important role. The behavioural and anatomical similarities found between HD and
      models using the mitochondrial toxin 3-nitropropionic acid (3NP) in rats and
      primates support this hypothesis. Here, we discuss the recently identified
      mechanisms of 3NP-induced striatal degeneration. Two types of important factor
      have been identified. The first are the 'executioner' components that have direct
      roles in cell death, such as c-Jun N-terminal kinase and Ca2+-activated protease
      calpains. The second are 'environmental' factors, such as glutamate, dopamine and
      adenosine, which modulate the striatal degeneration induced by 3NP.
      Interestingly, these recent studies support the hypothesis that 3NP and mutated
      Huntingtin have certain mechanisms of toxicity in common, suggesting that the use
      of 3NP might give new insights into the pathogenesis of HD. Research on 3NP
      provides additional proof that the neurochemical environment of a given neurone
      can determine its preferential vulnerability in neurodegenerative diseases.

PMID- 16300644
TI  - Biophysical characterization of longer forms of amyloid beta peptides: possible
      contribution to flocculent plaque formation.
AB  - Alzheimer's disease is characterized by amyloid deposits in the parenchyma and
      vasculature of the brain. The plaques are mainly composed of amyloid beta (Abeta)
      peptides ending in residues 40 and 42. Novel longer Abeta peptides were found in
      brain homogenates of mouse models of Alzheimer's disease and human brain tissue
      of patients carrying the familial amyloid precursor protein V717F mutation. The
      biophysical characteristics of these longer Abeta peptides and their role in
      plaque formation are not understood. We chose to focus our studies on Abeta
      peptides ending in residues Ile45, Val46 and Ile47 as these peptides were
      identified in human brain tissue. A combination of circular dichroism and
      electron microscopy was used to characterize the secondary and tertiary
      structures of these peptides. All three longer Abeta peptides consisted mainly of
      a beta-sheet secondary structure. Electron microscopy demonstrated that these
      beta-structured peptides formed predominantly amorphous aggregates, which convert
      to amyloid fibres over extended time periods. As these longer peptides may act as
      seeds for the nucleation of fibrils composed predominantly of shorter amyloid
      peptides, these interactions were studied. All peptides accelerated the random to
      beta-structural transitions and fibril formation of Abeta40 and 42.

PMID- 16300643
TI  - Comprehensive regional and temporal gene expression profiling of the rat brain
      during the first 24 h after experimental stroke identifies dynamic ischemia
      induced gene expression patterns, and reveals a biphasic activation of genes in
      surviving tissue.
AB  - In order to identify biological processes relevant for cell death and survival in
      the brain following stroke, the postischemic brain transcriptome was studied by a
      large-scale cDNA array analysis of three peri-infarct brain regions at eight time
      points during the first 24 h of reperfusion following middle cerebral artery
      occlusion in the rat. K-means cluster analysis revealed two distinct biphasic
      gene expression patterns that contained 44 genes (including 18 immediate early
      genes), involved in cell signaling and plasticity (i.e. MAP2K7, Sprouty2, Irs-2,
      Homer1, GPRC5B, Grasp). The first gene induction phase occurred at 0-3 h of
      reperfusion, and the second at 9-15 h, and was validated by in situ
      hybridization. Four gene clusters displayed a progressive increase in expression
      over time and included 50 genes linked to cell motility, lipid synthesis and
      trafficking (i.e. ApoD, NPC1, G3P-dehydrogenase1, and Choline kinase) or cell
      death-regulating genes such as mitochondrial CLIC. We conclude that a biphasic
      transcriptional up-regulation of the brain-derived neurotrophic factor (BDNF)-G
      protein coupled receptor (GPCR)-mitogen-activated protein (MAP) kinase signaling
      pathways occurs in surviving tissue, concomitant with a progressive and
      persistent activation of cell proliferation signifying tissue regeneration, which
      provide the means for cell survival and postischemic brain plasticity.

PMID- 16300645
TI  - Consequence of the presence of two different beta subunit isoforms in a GABA(A)
      receptor.
AB  - The major isoforms of GABA(A) receptors are thought to be composed of two alpha,
      two beta and one gamma subunit(s). GABA(A) receptors containing two beta1
      subunits respond differently to the anticonvulsive compound loreclezole and the
      general anaesthetic etomidate than receptors containing two beta2 subunits.
      Receptors containing beta2 subunits show a much larger allosteric stimulation by
      these agents than those containing beta1 subunits. We were interested to know how
      receptors containing both beta1 and beta2 subunits, in different positions
      respond to loreclezole and etomidate. To answer this question, subunits were
      fused at the DNA level to form dimeric and trimeric subunits. Concatenated
      receptors (alpha1-beta1-alpha1/gamma2-beta1, alpha1-beta2-alpha1/gamma2-beta1,
      alpha1-beta1-alpha1/gamma2-beta2 and alpha1-beta2-alpha1/gamma2-beta2) were
      expressed in Xenopus ooctyes and functionally compared in their response to the
      agonist GABA and to the positive allosteric modulators, loreclezole and
      etomidate. We have shown that (I) in the presence of both beta1 and beta2
      subunits in the same pentamer (mixed receptors) direct gating by etomidate is
      similar to exclusively beta1 containing receptors; (II) In mixed receptors,
      stimulation by etomidate assumed characteristics intermediate to exclusively
      beta1 or beta2 containing receptors, but the values for the concentrations < 10
      microM were always much closer to those observed in alpha1-beta1-alpha1/gamma2
      beta1 receptors; and (III) mixed receptors show no positional effects.

PMID- 16300647
TI  - Emerging themes of cancer stem cells: editorial--overview.

PMID- 16300646
TI  - Regulation of spinophilin Ser94 phosphorylation in neostriatal neurons involves
      both DARPP-32-dependent and independent pathways.
AB  - Spinophilin is a protein phosphatase-1 (PP-1)- and actin-binding protein that is
      enriched in dendritic spines. Phosphorylation of the actin-binding domain of rat
      spinophilin at one or more sites by protein kinase A (PKA) inhibits actin
      binding. Here, we investigated the regulation of mouse spinophilin that contains
      only a single PKA-site (Ser94) within its actin-binding domain. In vitro
      phosphorylation of Ser94 resulted in the dissociation of spinophilin from actin
      filaments. In mouse neostriatal slices, phospho-Ser94 (p-Ser94) was
      dephosphorylated mainly by PP-1 and also by PP-2A. Activation of dopamine D1
      receptors in striatonigral medium spiny neurons, and of adenosine A 2A receptors
      in striatopallidal medium spiny neurons increased, whereas activation of dopamine
      D2 receptors in striatopallidal neurons decreased, spinophilin Ser94
      phosphorylation. In neostriatal slices from DARPP-32 (dopamine- and cAMP
      regulated phosphoprotein of 32 kDa) knockout mice, the effects of D1, D2 and A 2A
      receptors were largely attenuated. Activation of NMDA receptors decreased Ser94
      phosphorylation in a PP-2A-dependent, but DARPP-32-independent, manner. These
      results suggest that PKA-dependent phosphorylation of spinophilin at Ser94 in
      both striatonigral and striatopallidal neurons requires synergistic contributions
      from the PKA and DARPP-32/PP-1 pathways. In addition, PP-2A plays a role in Ser94
      dephosphorylation in response to activation of both D2 and NMDA receptors.

PMID- 16300648
TI  - Retention of stem cell patterns in malignant cell lines.

PMID- 16300649
TI  - Cancer stem cells: lessons from leukaemia.
AB  - Increasing evidence suggests that leukaemias are sustained by leukaemic stem
      cells. Leukaemia can indeed be viewed as aberrant haematopoietic processes
      initiated by rare leukaemic stem cells that have maintained or re-acquired the
      capacity for indefinite proliferation through accumulated mutations and/or
      epigenetic changes. Yet, despite their critical importance, much remains to be
      learned about the developmental origin of leukaemic stem cells and the molecular
      pathways underlying the transformation of normal cells into leukaemic stem cells.
      This report will review our current knowledge on leukaemic stem cells development
      and finally demonstrate how these discoveries provide a paradigm for
      identification of cancer stem cells from solid tumours.

PMID- 16300650
TI  - Prostate epithelial stem cells.
AB  - The prostate gland is the site of the most commonly diagnosed cancer in men in
      USA and UK, accounting for one in five of new cases of male cancer. Common with
      many other cancer types, prostate cancer is believed to arise from a stem cell
      that shares characteristics with the normal stem cell. Normal prostate epithelial
      stem cells were recently identified and found to have a basal cell phenotype
      together with expression of CD133. Preliminary data have now emerged for a
      prostate cancer stem cell that also expresses cell surface CD133 but lacks
      expression of the androgen receptor. Here we examine the evidence supporting the
      existence of prostate cancer stem cells and discuss possible mechanisms of stem
      cell maintenance.

PMID- 16300651
TI  - Isolation and characterization of human mammary stem cells.
AB  - Since stem cells are present throughout the lifetime of an organism, it is
      thought that they may accumulate mutations, eventually leading to cancer. In the
      breast, tumours are predominantly oestrogen and progesterone receptor-positive
      (ERalpha/PR+). We therefore studied the biology of ERalpha/PR-positive cells and
      their relationship to stem cells in normal human mammary epithelium. We
      demonstrated that ERalpha/PR-positive cells co-express the putative stem cell
      markers p21(CIP1/WAF1), cytokeratin (CK) 19 and Musashi-1 when examined using
      dual label immunofluorescence on tissue sections. Next, we isolated a Hoechst dye
      effluxing 'side population' (SP) from the epithelium using flow cytometry and
      demonstrated them to be undifferentiated cells by lack of expression of
      myoepithelial and luminal cell-specific antigens such as CALLA and MUC1.
      Epithelial SP cells were shown to be enriched for the putative stem cell markers
      p21(CIP1/WAF1), Musashi-1 and ERalpha/PR-positive cells. Lastly, SP cells,
      compared to non-SP, were highly enriched for the capacity to produce colonies
      containing multiple lineages in 3D basement membrane (Matrigel) culture. We
      conclude that breast stem cells include two populations: a primitive ERalpha/PR
      negative stem cell necessary for development and a shorter term ERalpha/PR
      positive stem cell necessary for adult tissue homeostasis during menstrual
      cycling. We speculate these two basic stem cell types may therefore be the cells
      of origin for ERalpha-positive and -negative breast tumours.

PMID- 16300652
TI  - From gene mutations to tumours--stem cells in gastrointestinal carcinogenesis.
AB  - Stem cells share many properties with malignant cells, such as the ability to
      self-renew and proliferate. Cancer is believed to be a disease of stem cells. The
      gastrointestinal tract has high cancer prevalence partly because of rapid
      epithelial cell turnover and exposure to dietary toxins. The molecular pathways
      of carcinogenesis differ according to the tissue. Work on hereditary cancer
      syndromes including familial adenomatous polyposis (FAP) has led to advances in
      our understanding of the events that occur in tumour development from a
      gastrointestinal stem cell. The initial mutation involved in the adenoma
      carcinoma sequence is in the 'gatekeeper' tumour-suppressor gene adenomatous
      polyposis coli (APC). Somatic hits in this gene are non-random in FAP, with the
      type of mutation selected for by the position of the germline mutation. In the
      stomach, a metaplasia-dysplasia sequence occurs and is often related to
      Helicobacter pylori infection. Clonal expansion of mutated cells occurs by niche
      succession. Further expansion of the aberrant clone then occurs by the
      longitudinal division of crypts into two daughter units--crypt fission. Two
      theories seek to explain the early development of adenomas--the 'top down' and
      'bottom up' hypotheses. Initial studies suggested that colorectal tumours were
      monoclonal; however, later work on chimeric mice and a sex chromosome mixoploid
      patient with FAP suggested that up to 76% of early adenomas were polyclonal.
      Introduction of a homozygous resistance allele has reduced tumour multiplicity in
      the mouse and has been used to rule out random collision of polyps as the cause
      of these observations. It is likely that short-range interaction between adjacent
      initiated crypts is responsible for polyclonality.

PMID- 16300653
TI  - Liver cancer: the role of stem cells.
AB  - Studies of aggregation chimaeras and X-linked polymorphisms strongly suggest that
      liver tumours are derived from single cells (monoclonal), but the important
      question is, which cell? Stem cell biology and cancer are inextricably linked. In
      continually renewing tissues such as the gut mucosa and epidermis, where a steady
      flux of cells occurs from the stem cell zone to the terminally differentiated
      cells that are imminently to be lost, it is widely accepted that cancer is a
      disease of stem cells, since these are the only cells that persist in the tissue
      for a sufficient length of time to acquire the requisite number of genetic
      changes for neoplastic development. In the liver the identity of the founder
      cells for the two major primary tumours, hepatocellular carcinoma and
      cholangiocarcinoma, is more problematic. The reason for this is that no such
      obvious unidirectional flux occurs in the liver, although it is held that the
      centrilobular hepatocytes may be more differentiated (polyploid) and closer to
      cell senescence than those cells closest to the portal areas. Moreover, the
      existence of bipotential hepatic progenitor cells, along with hepatocytes endowed
      with longevity and long-term repopulating potential suggests there may be more
      than one type of carcinogen target cell. Cell proliferation at the time of
      carcinogen exposure is pivotal for 'fixing' any genotoxic injury into a heritable
      form, thus any proliferative cell in the liver can be susceptible to neoplastic
      transformation. Hepatocytes are implicated in many instances of hepatocellular
      carcinoma, direct injury to the biliary epithelium implicates cholangiocytes in
      some cases of cholangiocarcinoma, while hepatic progenitor cell/oval cell
      activation accompanies many instances of liver damage irrespective of aetiology,
      making such cells very likely carcinogen targets. Of course, we must qualify this
      assertion by stating that many carcinogens are both cytotoxic and cytostatic, and
      that hepatic progenitor cell proliferation may be merely a bystander effect of
      this toxicity. An in-depth discussion of causes of cancer in the liver is beyond
      the scope of this review, but infectious agents (e.g. hepatitis B and C viruses)
      play a major role, not just in transactivating or otherwise disrupting cellular
      proto-oncogenes (hepatitis B virus), but also in causing chronic inflammation
      (hepatitis C and B viruses). Sustained epithelial proliferation in a milieu rich
      in inflammatory cells, growth factors and DNA-damaging agents (reactive oxygen
      and nitrogen species--produced to fight infection), will lead to permanent
      genetic changes in proliferating cells. Up-regulation of the transcription factor
      NF-kappaB in transformed hepatocytes, through the paracrine action of TNF-alpha
      from neighbouring endothelia and inflammatory cells, may be critical for tumour
      progression given the mitogenic and antiapoptotic properties of proteins encoded
      by many of NF-kappaB's target genes.

PMID- 16300654
TI  - Cancer stem cells in the mammalian central nervous system.
AB  - Malignant tumours intrinsic to the central nervous system (CNS) are among the
      most difficult of neoplasms to treat effectively. The major biological features
      of these tumours that preclude successful therapy include their cellular
      heterogeneity, which renders them highly resistant to both chemotherapy and
      radiotherapy, and the propensity of the component tumour cells to invade,
      diffusely, the contiguous nervous tissues. The tumours are classified according
      to perceived cell of origin, gliomas being the most common generic group. In the
      1970s transplacental administration of the potent neurocarcinogen, N-ethyl-N
      nitrosourea (ENU), enabled investigation of the sequential development of brain
      and spinal neoplasms by electron microscopy and immunohistochemistry. The
      significance of the primitive cells of the subependymal plate in cellular origin
      and evolution of a variety of glial tumours was thereby established. Since then,
      the development of new cell culture methods, including the in vitro growth of
      neurospheres and multicellular tumour spheroids, and new antigenic markers of
      stem cells and glial/neuronal cell precursor cells, including nestin, Mushashi-1
      and CD133, have led to a reappraisal of the histological classification and
      origins of CNS tumours. Moreover, neural stem cells may also provide new vectors
      in exciting novel therapeutic strategies for these tumours. In addition to the
      gliomas, stem cells may have been identified in paediatric tumours including
      cerebellar medulloblastoma, thought to be of external granule cell neuronal
      derivation. Interestingly, while the stem cell marker CD133 is expressed in these
      primitive neuroectodermal tumours (PNETs), the chondroitin sulphate proteoglycan
      neuronal/glial 2 (NG2), which appears to denote increased proliferative, but
      reduced migratory activity in adult gliomas, is rarely expressed. This is in
      contrast to the situation in the histologically similar supratentorial PNETs. A
      possible functional 'switch' between proliferation and migration in developing
      neural tumour cells may exist between NG2 and ganglioside GD3. The divergent
      pathways of differentiation of CNS tumours and the possibility of stem cell
      origin, for some, if not all, such neoplasms remain a matter for debate and
      continued research, but the presence of self-renewing neural stem cells in the
      CNS of both children and adults strongly suggests a role for these cells in
      tumour initiation and resistance to current therapeutic strategies.

PMID- 16300655
TI  - Energy and fibre intake in a group of captive giraffe (Giraffa camelopardalis)
      offered increasing amounts of browse.
AB  - We investigated the effect of diet on intake of energy and fibre in a group of
      three captive adult giraffe by weighing offered diet items and leftovers for 7
      days after an adaptation period of 7 days. Digestion coefficients were calculated
      using, as internal marker, the acid detergent lignin content of a faecal sample
      pooled from subsamples taken during the last 5 days of intake measurement. Two
      lucerne hay-only diets of differing quality (L1, L2) were fed, as well as the
      regular diet of lucerne hay and concentrates (L2C), and the regular diet
      supplemented with 3 or 6 kg of edible, fresh browse material (L2CB3, L2CB6). The
      proportion of roughage in the ingested diets L2CB6 (45 +/- 5% dry matter), L2CB3
      (35 +/- 3%) and L2C (37 +/- 10%) did not differ significantly. Digestible energy
      intake was low on the hay-only diets [L1: 0.28 +/- 0.06 MJ/kg body weight
      (BW)0.75; L2: 0.33 +/- 0.10 MJ/kg BW0.75] and increased from L2C (0.60 +/- 0.13
      MJ/kg BW0.75) to a significant increase with L2CB3 (0.72 +/- 0.17 MJ/kg BW0.75);
      no further increase was obvious for L2CB6 (0.63 +/- 0.15MJ/kg BW0.75). The
      results confirm that giraffes are unlikely to meet energy requirements on lucerne
      hay-only diets. In a feeding scenario where both lucerne hay and the concentrate
      component of the diet are fed ad libitum, the animals tended to exchange hay for
      browse when browse was added. Only the higher level of browse supplementation led
      to a potentially beneficial increase in fibre intake. Whether additional browse
      supplementation will lead to increased intakes in a feeding scenario with
      restricted concentrate provision can be suspected but remains to be demonstrated.

PMID- 16300656
TI  - Abundance of mRNA of growth hormone receptor and insulin-like growth factors-1
      and -2 in duodenal and colonic biopsies of dogs with chronic enteropathies*.
AB  - Repair processes of the inflamed intestine are very important for dissolution of
      chronic enteropathies (CE). Therefore, we examined the mRNA abundance of growth
      hormone receptor (GHR), insulin-like growth factors (IGF)-1 and -2 in duodenal
      and colonic biopsies of dogs with CE such as food-responsive diarrhoea (FRD) and
      inflammatory bowel disease (IBD) before and after treatment as compared with each
      other and healthy dogs. A clinical score (Canine IBD Activity Index = CIBDAI) was
      applied to judge the severity of CE. Biopsies of duodenum and colon from client
      owned dogs with CE were sampled before (FRD(bef), n = 5; IBD(bef), n = 5) and
      after treatment (FRD(aft), n = 5; IBD(aft), n = 5). Intestinal control samples
      were available from a homogenous control population (n = 15; C). Intestinal
      samples were homogenized, total RNA was extracted, reverse transcribed and
      analysed by real-time polymerase chain reaction to measure mRNA levels of GHR,
      IGF-1 and IGF-2. Results were normalized with glyceraldehyde phosphate
      dehydrogenase as housekeeping gene. The CIBDAI decreased during the treatment
      period in FRD and IBD (P < 0.01). In duodenum, GHR mRNA levels were higher in all
      groups than in C (P < 0.001). Duodenal IGF-1 mRNA levels in FRD(aft) and IBD(aft)
      tended to be higher than in C (P < 0.1). The IGF-2 mRNA abundance in FRD(aft) was
      higher than in C (P < 0.05) in duodenum. In colon, mRNA levels of IGF-1 in
      IBD(aft) were higher than in FRD(aft) (P < 0.05) and levels differed between
      IBD(aft) and C (P < 0.05). In conclusion, mRNA levels of GHR, IGF-1 and IGF-2 in
      the gastrointestinal tract were increased during CE when compared with
      gastrointestinally healthy dogs. The data suggest that GHR, IGF-1 and IGF-2 are
      involved in gastrointestinal repair processes.

PMID- 16300657
TI  - Alpha1-adrenoceptor-mediated negative inotropic effect caused by intracellular
      ionic activities in guinea-pig papillary muscle.
AB  - In guinea-pig papillary muscle, phenylephrine (PE), an agonist of alpha1
      adrenoceptor (alpha1-AR), led to a transient negative inotropic effect (NIE) and
      a subsequent sustained positive inotropic effect (PIE). To clarify the ionic
      mechanisms underlying the NIE, we measured the [Na+]i or [pH]i by ion-selective
      microelectrodes. PE produced a decrease in the intracellular Na+ concentration
      ([Na+]i) and an increase in intracellular pH ([pH]i). During the phase of NIE, PE
      produced only a (-) change of [Na+]i (Delta[Na+]i). With a decrease in
      extracellular Na+ or an increase in extracellular Ca2+, the PE-induced NIE was
      attenuated and PE produced (+)Delta[Na+]i. The PE-induced NIE and (-)Delta[Na+]i
      were definitely strengthened by lowering the bath temperature or increasing the
      stimulation frequency. 2-(2,6-di-methoxyphenoxyethyl)amino-methyl-1,4
      benzidioxane HCl, an antagonist of alpha1A-AR, completely abolished the PE
      induced NIE and (-)Delta[Na+]i. Phorbol 12,13-dibutyrate, an activator of protein
      kinase C (PKC), decreased the baseline [Na+]i and twitch force and increased the
      baseline [pH]i in mimicry of PE. Pretreatment with 1-5(isoquinolinesulphonyl)-2
      methylpiperazine, an inhibitor of PKC, abolished the PE-induced NIE and (
      )Delta[Na+]i. During pretreatment with benzamil, an inhibitor of Na+/Ca2+
      exchange, we found that the PE-induced NIE and (-)Delta[Na+]i were reversibly
      abolished. Our results indicate the PE-induced NIE may be elicited upon the
      activation of Na+/Ca2+ exchange which can be attributed to the (-)Delta[Na+]i. (
      )Delta[Na+]i is mediated through a PKC-dependent pathway via an activation of
      alpha1A-AR subtype and its effect could be strengthened remarkably at high [Na+]i
      and [Ca2+]i values.

PMID- 16300658
TI  - The occurrence of nymphal stage of Linguatula serrata in water buffaloes (Bubalus
      bubalis): nymphal morphometry and lymph node pathology.
AB  - The mesenteric lymph nodes (MLN) of buffaloes (n = 100) were examined for the
      presence of parasitic infection. The nymphal stage of Linguatula serrata was
      observed in two buffaloes. A single white-coloured nymph with transversely
      striated spines on a segmented body, two pairs of oral suckers and hooks was
      observed in the MLN. The morphometrics of the nymphs were studied. The affected
      lymph nodes were grossly enlarged with cyst and showed pathological lesions of
      fibroblastic reaction with a mild underlying inflammatory zone.

PMID- 16300659
TI  - Pulmonary adenosquamous carcinoma in a dog.
AB  - A mass that developed in the lung of a 10-year-old mixed-breed dog was
      pathologically examined. Histopathological examination showed papillary and
      tubular growth of glandular epithelium-like cells in some areas and growth of
      squamous cells arranged in nests in other areas, showing coexistence of
      adenocarcinoma and squamous cell carcinoma in a lung tumour. Immunohistochemical
      staining with anti-keratin-cytokeratin antibody was strongly positive for
      cytoplasms in both components. Electron microscopically, the neoplastic cells of
      the adenocarcinoma component had features of glandular cells, with microvilli,
      numerous free ribosomes, large round secretory granules and intercellular
      desmosomes. Non-keratinized squamous cells had tonofilaments and intercellular
      desmosomes. These findings led to the diagnosis of primary adenosquamous
      carcinoma, which demonstrates phenotypic profiles characteristic of both
      epidermal keratinocytes and glandular epithelium.

PMID- 16300660
TI  - Cytological diagnosis of mandibular salivary gland adenocarcinoma in a dog.
AB  - A case of mandibular salivary gland adenocarcinoma in a 9-year-old female dog is
      described. Material collected by fine needle aspiration underwent cytological
      examination and after the diagnosis of salivary carcinoma the mass was surgically
      excised and then was processed for histological examination. The aim of this work
      is to describe the cytopathological features of this carcinoma and to emphasize
      the usefulness of fine needle aspiration technique, which is an effective,
      inexpensive and minimally invasive method of diagnosis that can be performed
      before incisional biopsy or even before surgical excision.

PMID- 16300661
TI  - The role of first line of defence mechanisms in the pathogenesis of cellulitis in
      broiler chickens: skin structural, physiological and cellular response factors.
AB  - The present study examined several basic attributes of first-line defence
      mechanisms in the skin as potential factors that may explain the susceptibility
      of broiler chickens to cellulitis. The variables including structural
      characteristics of the skin, physicochemical properties and cellular responses to
      the challenge with pathogens were compared between two categories of chickens, a
      strain of fast-growing commercial broiler chickens (susceptible to cellulitis)
      and leghorn chickens (resistant to cellulitis). There were substantial
      differences between leghorns and broilers with regard to physiological
      characteristics of the skin. Broiler skin was more amenable to injury and the
      wound-healing process was slow. Compared with leghorns, the lesions resulting
      from sub-dermal challenge in broilers were more severe and disseminated over a
      larger area. Mobilization of phagocytic cells (heterophils and macrophages) in
      leghorns was brisk even in the areas distant from the site of infection, whereas
      only few heterophils were recruited in the skin of broilers. The functional
      competence of heterophils in broilers was inferior when compared with leghorns.
      Based on the present finding, the predisposition of broilers to cellulitis
      appears to be primarily associated with the inferior first line of defence of
      their skin. Broilers in commercial situations may be at higher risk to succumb to
      even minor infection and eventually develop cellulitis because: (1) structural
      weaknesses of the skin may predispose broilers to skin injury and thus the risk
      of skin infection by pathogens is increased; (2) broiler skin surface is more
      likely to provide a conducive environment for colonization of Escherichia coli;
      (3) in the event of infection, poor recruitment of phagocytic cells to the site
      of infection may readily lead to widespread colonization of the tissue by
      pathogens causing cellulitis and (4) poor functional quality of the phagocytic
      cells that are mobilized compromise the ability of the host to contain the spread
      of infection.

PMID- 16300662
TI  - Tolerance of therapeutic doses of abamectin and doramectin in Istrian Pramenka
      sheep.
AB  - Avermectin endectocides are very effective and safe veterinary drugs, when used
      at recommended doses. Adverse reactions are described in some species and breeds
      of animals. In this study, the effects of therapeutic doses of abamectin and
      doramectin on some haematological and biochemical parameters in Istrian Pramenka
      sheep are discussed. In the pilot trial, we compared selected haematological and
      blood biochemical parameters of an experimental sheep flock (40 sheep) with the
      reference values. Then, two groups of 12 sheep (and their suckling lambs) were
      chosen from the experimental sheep flock. Each group was subdivided into a
      control (six animals) and treated (six sheep and their six suckling lambs)
      groups. We compared haematological and biochemical parameters between control and
      treated group before subcutaneous administration of abamectin or doramectin (0.2
      mg/kg b.w.) and on days 15 and 42 after treatment. In addition, animals were
      observed for neurological signs. We detected some significant differences (P <
      0.05) in some haematological and biochemical parameters between control and
      treated animals, but none of them appeared to be of clinical importance. No
      neurological symptoms were observed. Therefore, abamectin and doramectin might be
      well tolerated in Istrian Pramenka sheep.

PMID- 16300663
TI  - Epidemiologic risk factors for chronic prostatitis.
AB  - Chronic prostatitis/chronic pelvic pain syndrome is a multifactorial problem,
      which affects men of all ages and in all demographics. Recent studies have shown
      that the prevalence of prostatitis is approximately 2-10% among unselected men in
      North America, Europe and Asia. This data clearly indicates that chronic
      prostatitis constitutes an important problem in international health care.
      Nevertheless, the aetiology and pathogenesis of chronic prostatitis have yet to
      be clearly delineated, despite the numerous efforts which have been made, with
      regard to both basic and clinical research. In fact, factors other than
      leucocytes and bacteria have been shown to contribute to the symptoms typically
      associated with prostatitis. Studies of the epidemiology and determinants of
      prostatitis risk factors may also provide clues to the general aetiology of
      prostatitis. Other epidemiological data appears to indicate that certain as-yet
      unknown factors might be associated with an increased tendency towards the
      development of chronic prostatitis. However, findings from most studies are
      considered to represent only preliminary data, because of the small sample sizes
      or lack of generalizability inherent to most of the studies. The identification
      and characterization of these relevant risk factors might accelerate or augment
      the development of preventive, diagnostic, and therapeutic strategies for the
      treatment of these syndromes.

PMID- 16300664
TI  - Low total normal motile count values are associated with increased sperm disomy
      and diploidy rates in infertile patients.
AB  - This study was undertaken to evaluate the possibility of identifying men at
      increased risk of sperm aneuploidy and diploidy on the bases of specific cut-off
      values of the total normal motile count (TNMC). Twenty-seven consecutive,
      unselected male patients referred to our Unit were studied: 11 patients with
      normal sperm parameters (group A) suffering from unexplained infertility and 16
      infertile patients with abnormal sperm parameters (group B). Disomy rates for
      chromosomes 1, 4, 8, 12, 18, X and Y were ascertained for each patient by means
      of triple and double fluorescence in situ hybridization (FISH) experiments. Both
      univariate and multivariate statistical analyses by principal component analysis
      (PCA) were performed for comparisons between sperm aneuploidy rates and semen
      quality (TNMC). TNMC scores in the two groups were significantly different (23.5
      x 10(6) and 1.52 x 10(6), in groups A and B, respectively, p = 0.00002). In
      general, higher sperm disomy rates were noted for all chromosomes in group B
      compared with group A. Statistical significance was observed for disomy 1, total
      disomy rate (3.36% vs. 1.38%), and diploidy (0.49% vs. 0.19%) (p < 0.01). For
      disomy 4 and 8, differences resulted close to significance. PCA clearly showed
      how independent variables were inter-related. Infertile men with TNMC < 2 x 10(6)
      (male factor) were found to be at increased risk for sperm aneuploidy and
      diploidy. Multivariate analysis by PCA resulted as a useful method to visualize
      the information of the data sets on a bi-dimensional plot considering all the
      patients and all the variables at the same time.

PMID- 16300665
TI  - Effects of leucocytospermia on semen parameters and outcomes of intracytoplasmic
      sperm injection.
AB  - Leucocytes are present throughout the male reproductive tract but the clinical
      significance of leucocytic infiltration in the human ejaculate is controversial.
      The World Health Organization (WHO) defines leucocytospermia as the presence of
      peroxidase-positive leucocytes in concentrations of > or =1 x 10(6)/mL of semen.
      The goals of this study were to clarify the relationship between leucocytospermia
      and semen parameters including sperm concentration, progressive and total
      motility before and after semen preparation, and intracytoplasmic sperm injection
      (ICSI) outcomes, including fertilization, embryo development, embryo morphology,
      cleavage and pregnancy rates. We compared the semen parameters and ICSI outcome
      of 34 leucocytospermic and 36 non-leucocytospermic control couples who were
      undergoing ICSI because of male factor infertility including oligo and/or astheno
      and/or teratozoospermia. Semen parameters including progressive motility rate
      (1.5% vs. 3%) and sperm concentrations (12 vs. 29 million/mL) were significantly
      lower in the leucocytospermic group compared with the control group. Other semen
      parameters were not affected by the presence of leucocytes. ICSI outcome,
      including fertilization (82% vs. 87%) and embryo development rates (79% vs. 86%)
      were significantly lower in the leucocytospermic group compared with the control
      group although there were no statistical difference for embryo quality, embryo
      cleavage and pregnancy rates. These results indicate that some semen parameters
      and the outcome of ICSI were negatively affected by the presence of
      leucocytospermia.

PMID- 16300666
TI  - Outcomes in couples undergoing ICSI: comparison between fresh and frozen-thawed
      surgically retrieved spermatozoa.
AB  - We retrospectively evaluated the impact of cryopreservation on spermatozoa
      obtained from patients with azoospermia and used for intracytoplasmic sperm
      injection (ICSI). Frozen-thawed epididymal spermatozoa (FTEPS) was used in 34
      couples, whereas frozen-thawed testicular spermatozoa (FTTS) was used in 50
      couples for ICSI during assisted conception, and these results were compared with
      results using fresh spermatozoa for ICSI in the same individuals. The
      fertilization rate (FR) was significantly lower for FTTS (65.8%) but not for
      FTEPS (73.1%) compared with the FR using fresh spermatozoa (72.3% and 73.2%
      respectively). In contrast, neither the implantation nor the pregnancy rate was
      altered when FTEPS or FTTS was used. In conclusion, our results indicate that
      surgically retrieved spermatozoa can be efficiently used for ICSI after freezing
      and thawing without compromising the outcome.

PMID- 16300667
TI  - Electric waves recorded from the testicle: are they capsular or from the
      testicular tissue?
AB  - We demonstrated in a previous study that electric waves could be recorded from
      the testicle by applying the electrodes either directly to the tunica albuginea
      (TA) or transcutaneously. As the TA contains smooth muscle fibres which
      presumably transmit the electric waves, we investigated the hypothesis that the
      electric waves recorded from the testicle originated from the TA. During the
      repair of inguino-scrotal hernia in 24 men [age 36.6 +/- 8.6 years (mean +/-
      SD)], the tunica vaginalis was everted because of the presence of hydrocele. The
      electric activity of the TA was recorded by three surface electrodes and that of
      the testicle by three needle electrodes. The recorded potentials were amplified
      and displayed on an electromyographic apparatus. Triphasic slow waves (SWs) were
      recorded from the TA. They showed similar frequency, amplitude and conduction
      velocity from the three electrodes of the individual subject and were
      reproducible. They were followed or superimposed by bursts of action potentials
      (APs) which occurred randomly. No waves were recorded from the three needle
      electrodes inserted into the testicular tissue. The current study could
      demonstrate that the electric waves recorded from the electrodes applied to the
      testicle were derived from the TA and not from the testicular tissue. This
      finding apparently denotes that the TA has a resting tone and probably motile
      activity, the role of which in testicular function needs to be studied.

PMID- 16300668
TI  - Magnetic resonance imaging of experimental testicular torsion.
AB  - We investigated the feasibility of contrast enhanced (CE)-dynamic magnetic
      resonance imaging (MRI) for the detection of testicular torsion induced
      hypoperfusion in an experimental rat model. Adult Sprague-Dawley rats were
      subjected to unilateral testicular torsion of 360 or 720 degrees. After 1 h, the
      tail veins of the anaesthetized rats were cannulated and T2 -, diffusion-weighted
      and T1-weighted CE-dynamic MRI were subsequently performed by a 1.5 T MRI
      scanner. On apparent diffusion coefficient (ADC) images, the region of interest
      values of the ischaemic and control testes was compared. From CE-dynamic MR
      images, the maximal slopes of contrast enhancement were calculated and compared.
      In testicular torsion of 360 degrees, the maximal slope of contrast enhancement
      was 0.072%/s vs. 0.47%/s in the contralateral control testis (p < 0.001). A
      torsion of 720 degrees diminished the slope of contrast enhancement to 0.046%/s
      vs. 0.37%/s in the contralateral testis (p < 0.001). Diminished blood flow during
      torsion also followed in decreased ADC values in both 360 degrees (12.4%
      decrease; p < 0.05) and 720 degrees (10.8% decrease; p < 0.001) of torsion.
      Torsion of the testis causes ipsilateral hypoperfusion and decreased gadolinium
      uptake in a rat model that can be easily detected and quantified by CE-dynamic
      MRI. In diffusion-weighted MRI images, acute hypoperfusion results in a slight
      decrease of ADC values. Our results suggest that CE-dynamic MRI in combination
      with diffusion-weighted MRI can be used to detect compromised blood flow due to
      acute testicular torsion.

PMID- 16300669
TI  - N-terminal region of progesterone receptor B isoform in human spermatozoa.
AB  - Progesterone is known to act on human spermatozoa by an unidentified membrane
      receptor. Previous studies have demonstrated the existence of transcripts of
      conventional progesterone receptor (PR) in sperm RNA; antibodies directed against
      the C-terminal region of the conventional PR recognize a protein in sperm
      extracts. The present study aimed at characterizing the sperm PR using probes
      unique to the N-terminal region of the PR-B isoform. PR-B transcripts that were
      homologous to the conventional PR were detected in sperm RNA and localized in the
      midpiece region. Using specific antibody against the N-terminal region of PR-B,
      strong immunoreactivity was observed on the acrosomal region of digitonin-treated
      spermatozoa; Western blot analysis revealed a single band of approximately 55
      kDa. Immunogold labelling studies using the same antibody localized the protein
      at the inner acrosomal membrane of testicular spermatids. This antibody blocked
      the binding of fluorescent-tagged progesterone to digitonin-treated spermatozoa
      and inhibited the progesterone-mediated kinase activation. The results of the
      present study gives an insight to speculate that the sperm membrane PR may have
      homology at the N-terminal region of the conventional PR-B isoform, or the
      membrane PR protein may share structural motifs that allows progesterone binding
      and interactions with the antibodies against the conventional PR.

PMID- 16300670
TI  - Interchromosomal effect in sperm of males with translocations: report of 6 cases
      and review of the literature.
AB  - Somatic chromosomal abnormalities are frequently found in infertile men,
      particularly in those with low sperm count and/or seeking intracytoplasmic sperm
      injection. These abnormalities mostly consist of numerical sex chromosome
      abnormalities and translocations (Robertsonian or reciprocal). In this study, we
      searched for the occurrence of non-disjunction of chromosomes not involved in
      translocations during meiosis, phenomenon called interchromosomal effect (ICE)
      and first described by Lejeune (1965). Ejaculate samples of two patients carrying
      a Robertsonian translocation and four a reciprocal translocation patients and
      four controls (men with a 46,XY karyotype and normal sperm parameters) were
      studied in dual FISH 7-9, dual FISH 13-21 and triple FISH X-Y-18. A statistically
      significant increase of disomy X, Y and XY (P = 0.009, P = 0.004, P < 0.001) was
      found in the Robertsonian der(13;14)(q10;q10) carrier but not in the
      der(14;21)(q10;q10) carrier compared with controls. Among reciprocal
      translocation carriers, a significant increase of disomy 21 (P = 0.033) was
      observed in a sole patient with a t(9;22)(q21;q11.2). The increase of meiotic non
      disjunction for chromosome 21 and sex chromosomes is a recurrent event found in
      other studies. According to our results and published data, the ICE on some
      specific chromosomes is likely in men carrier of a translocation, although it
      cannot be excluded that the aneuploidy is related to the
      oligoasthenoteratozoospermia usually present in these men. Moreover, this
      phenomenon showed interindividual variations which cannot be predicted. The risk
      of aneuploidy in sperm of males used for ICSI need to be evaluated. It could be
      superadded to that of meiotic segregation of the translocation to give a more
      precise and personalized risk assessment of aneuploidy in the offspring of those
      men.

PMID- 16300672
TI  - A systematic review of existing national priorities for child health research in
      sub-Saharan Africa.
AB  - BACKGROUND: We systematically reviewed existing national child health research
      priorities in Sub-Saharan Africa, and the processes used to determine them.
      METHODS: Collaborators from a purposive sample of 20 WHO-AFRO Region countries,
      assisted by key informants from a range of governmental, non-governmental,
      research and funding organisations and universities, identified and located
      potentially eligible prioritisation documents. Included documents were those
      published between 1990 and 2002 from national or nationally accredited
      institutions describing national health research priorities for child health,
      alone or as part of a broader report in which children were a clearly
      identifiable group. Laboratory, clinical, public health and policy research were
      included. Two reviewers independently assessed eligibility for inclusion and
      extracted data. RESULTS: Eight of 33 potentially eligible reports were included.
      Five reports focused on limited areas of child health. The remaining three
      included child-specific categories in reports of general research priorities,
      with two such child-specific categories limited to reproductive health. In a
      secondary analysis of Essential National Health Research reports that included
      children, though not necessarily as an identifiable group, the reporting of
      priorities varied markedly in format and numbers of priorities listed, despite a
      standard recommended approach. Comparison and synthesis of reported priorities
      was not possible. CONCLUSION: Few systematically developed national research
      priorities for child health exist in sub-Saharan Africa. Children's interests may
      be distorted in prioritisation processes that combine all age groups. Future
      development of priorities requires a common reporting framework and specific
      consideration of childhood priorities.

PMID- 16300673
TI  - New paradigms, new hopes: the need for socially responsible research on
      carcinogenesis.

PMID- 16300674
TI  - Insulin induces a positive relationship between the rates of ATP and glycogen
      changes in isolated rat liver in presence of glucose; a 31P and 13C NMR study.
AB  - BACKGROUND: There is an emerging theory suggesting that insulin, which is known
      to be the predominant postprandial anabolic hormone, is also a major regulator of
      mitochondrial oxidative phosphorylation in human skeletal muscle. However, little
      is known about its effects in the liver. Since there is a theoretical
      relationship between glycogen metabolism and energy status, a simultaneous and
      continuous investigation of hepatic ATP and glycogen content was performed in
      intact and isolated perfused liver by 31P and 13C nuclear magnetic resonance
      (NMR) The hepatic rates of ATP and glycogen changes were evaluated with different
      concentrations of insulin and glucose during continuous and short-term supply.
      RESULTS: Liver from rats fed ad libitum were perfused with Krebs-Henseleit Buffer
      (KHB)(controls) or KHB containing 6 mM glucose, 30 mM glucose, insulin alone,
      insulin + 6 mM glucose, insulin + 30 mM glucose. In the control, glycogenolysis
      occurred at a rate of -0.53 +/- 0.021 % x min(-1) and ATP content decreased at a
      rate of -0.28 +/- 0.029 % x min(-1). In the absence of insulin, there was a close
      proportional relationship between the glycogen flux and the glucose
      concentration, whereas ATP rates never varied. With insulin + glucose, both
      glycogen and ATP rates were strongly related to the glucose concentration; the
      magnitude of net glycogen flux was linearly correlated to the magnitude of net
      ATP flux: flux(glycogen) = 72.543(fluxATP) + 172.08, R2 = 0.98. CONCLUSION: Only
      the co-infusion of 30 mM glucose and insulin led to (i) a net glycogen synthesis,
      (ii) the maintenance of the hepatic ATP content, and a strong positive
      correlation between their net fluxes. This has never previously been reported.
      The specific effect of insulin on ATP change is likely related to a rapid
      stimulation of the hepatic mitochondrial oxidative phosphorylation. We propose
      that variations in the correlation between rates of ATP and glycogen changes
      could be a probe for insulin resistance due to the action of substrates, drugs or
      pathologic situations. Consequently, any work evaluating insulin resistance on
      isolated organs or in vivo should determine both ATP and glycogen fluxes.

PMID- 16300675
TI  - Functional inaccessibility of quiescent herpes simplex virus genomes.
AB  - BACKGROUND: Newly delivered herpes simplex virus genomes are subject to
      repression during the early stages of infection of human fibroblasts. This host
      defence strategy can limit virus replication and lead to long-term persistence of
      quiescent viral genomes. The viral immediate-early protein ICP0 acts to negate
      this negative regulation, thereby facilitating the onset of the viral replication
      cycle. Although few mechanistic details are available, the host repression
      machinery has been proposed to assemble the viral genome into a globally
      inaccessible configuration analogous to heterochromatin, blocking access to most
      or all trans-acting factors. The strongest evidence for this hypothesis is that
      ICP0-deficient virus is unable to reactivate quiescent viral genomes, despite its
      ability to undergo productive infection given a sufficiently high multiplicity of
      infection. However, recent studies have shown that quiescent infection induces a
      potent antiviral state, and that ICP0 plays a key role in disarming such host
      antiviral responses. These findings raise the possibility that cells containing
      quiescent viral genomes may be refractory to superinfection by ICP0-deficient
      virus, potentially providing an alternative explanation for the inability of such
      viruses to trigger reactivation. We therefore asked if ICP0-deficient virus is
      capable of replicating in cells that contain quiescent viral genomes. RESULTS: We
      found that ICP0-deficient herpes simplex virus is able to infect quiescently
      infected cells, leading to expression and replication of the superinfecting viral
      genome. Despite this productive infection, the resident quiescent viral genome
      was neither expressed nor replicated, unless ICP0 was provided in trans.
      CONCLUSION: These data document that quiescent HSV genomes fail to respond to the
      virally modified host transcriptional apparatus or viral DNA replication
      machinery provided in trans by productive HSV infection in the absence of ICP0.
      These results point to global repression as the basis for HSV genome quiescence,
      and indicate that ICP0 induces reactivation by overcoming this global barrier to
      the access of trans-acting factors.

PMID- 16300676
TI  - Efficient gene-driven germ-line point mutagenesis of C57BL/6J mice.
AB  - BACKGROUND: Analysis of an allelic series of point mutations in a gene, generated
      by N-ethyl-N-nitrosourea (ENU) mutagenesis, is a valuable method for discovering
      the full scope of its biological function. Here we present an efficient gene
      driven approach for identifying ENU-induced point mutations in any gene in
      C57BL/6J mice. The advantage of such an approach is that it allows one to select
      any gene of interest in the mouse genome and to go directly from DNA sequence to
      mutant mice. RESULTS: We produced the Cryopreserved Mutant Mouse Bank (CMMB),
      which is an archive of DNA, cDNA, tissues, and sperm from 4,000 G1 male offspring
      of ENU-treated C57BL/6J males mated to untreated C57BL/6J females. Each mouse in
      the CMMB carries a large number of random heterozygous point mutations throughout
      the genome. High-throughput Temperature Gradient Capillary Electrophoresis (TGCE)
      was employed to perform a 32-Mbp sequence-driven screen for mutations in 38 PCR
      amplicons from 11 genes in DNA and/or cDNA from the CMMB mice. DNA sequence
      analysis of heteroduplex-forming amplicons identified by TGCE revealed 22
      mutations in 10 genes for an overall mutation frequency of 1 in 1.45 Mbp. All 22
      mutations are single base pair substitutions, and nine of them (41%) result in
      nonconservative amino acid substitutions. Intracytoplasmic sperm injection (ICSI)
      of cryopreserved spermatozoa into B6D2F1 or C57BL/6J ova was used to recover
      mutant mice for nine of the mutations to date. CONCLUSIONS: The inbred C57BL/6J
      CMMB, together with TGCE mutation screening and ICSI for the recovery of mutant
      mice, represents a valuable gene-driven approach for the functional annotation of
      the mammalian genome and for the generation of mouse models of human genetic
      diseases. The ability of ENU to induce mutations that cause various types of
      changes in proteins will provide additional insights into the functions of
      mammalian proteins that may not be detectable by knockout mutations.

PMID- 16300677
TI  - Evaluating changeability to improve fruit and vegetable intake among school aged
      children.
AB  - BACKGROUND: The purposes of this paper are two fold. First, to describe an
      approach used to identify fruits and vegetables to target for a child focused
      dietary change intervention. Second, to evaluate the concept of fruit and
      vegetable changeability and feasibility of applying it in a community setting.
      METHODS: Steps for identifying changeable fruits and vegetables include (1)
      identifying a dietary database (2) defining geographic and (3) personal
      demographics that characterize the food environment and (4) determining which
      fruits and vegetables are likely to improve during an intervention. The validity
      of these methods are evaluated for credibility using data collected from quasi
      experimental, controlled design among 7-9 year old children (n = 304)
      participating in a tutoring or mentoring program in St. Louis, MO. Using a 28
      item food frequency questionnaire, parents were asked to recall for their child
      how often foods were eaten the past 7 days. This questionnaire was repeated eight
      months later (response rate 84%). T-test analyses are used to determine mean
      serving differences from baseline to post test. RESULTS: The mean serving
      differences from baseline to post test were significant for moderately eaten
      fruits (p < .001), however, not for vegetables (p = .312). Among the intervention
      group, significantly more children ate grapes (p < .001), peaches (p = .022),
      cantaloupe (p < .001), and spinach (p = .044) at post testing - all identified as
      changeable with information tailored to participants. CONCLUSION: Data driven,
      food focused interventions directed at a priority population are feasible and
      practical. An empirical evaluation of the assumptions associated with these
      methods supports this novel approach. However, results may indicate that these
      methods may be more relevant to fruits than vegetables. This process can be
      applied to diverse populations for many dietary outcomes. Intervention strategies
      that target only those changeable fruits and vegetables are innovative and
      warrant further study.

PMID- 16300678
TI  - Stimulation of poliovirus RNA synthesis and virus maturation in a HeLa cell-free
      in vitro translation-RNA replication system by viral protein 3CDpro.
AB  - Poliovirus protein 3CDpro possesses both proteinase and RNA binding activities,
      which are located in the 3Cpro domain of the protein. The RNA polymerase (3Dpol)
      domain of 3CDpro modulates these activities of the protein. We have recently
      shown that the level of 3CDpro in HeLa cell-free in vitro translation-RNA
      replication reactions is suboptimal for efficient virus production. However, the
      addition of either 3CDpro mRNA or of purified 3CDpro protein to in vitro
      reactions, programmed with viral RNA, results in a 100-fold increase in virus
      yield. Mutational analyses of 3CDpro indicated that RNA binding by the 3Cpro
      domain and the integrity of interface I in the 3Dpol domain of the protein are
      both required for function. The aim of these studies was to determine the exact
      step or steps at which 3CDpro enhances virus yield and to determine the mechanism
      by which this occurs. Our results suggest that the addition of extra 3CDpro to in
      vitro translation RNA-replication reactions results in a mild enhancement of both
      minus and plus strand RNA synthesis. By examining the viral particles formed in
      the in vitro reactions on sucrose gradients we determined that 3CDpro has only a
      slight stimulating effect on the synthesis of capsid precursors but it strikingly
      enhances the maturation of virus particles. Both the stimulation of RNA synthesis
      and the maturation of the virus particles are dependent on the presence of an
      intact RNA binding site within the 3Cpro domain of 3CDpro. In addition, the
      integrity of interface I in the 3Dpol domain of 3CDpro is required for efficient
      production of mature virus. Surprisingly, plus strand RNA synthesis and virus
      production in in vitro reactions, programmed with full-length transcript RNA, are
      not enhanced by the addition of extra 3CDpro. Our results indicate that the
      stimulation of RNA synthesis and virus maturation by 3CDpro in vitro is dependent
      on the presence of a VPg-linked RNA template.

PMID- 16300679
TI  - Phylogenetic analyses suggest reverse splicing spread of group I introns in
      fungal ribosomal DNA.
AB  - BACKGROUND: Group I introns have spread into over 90 different sites in nuclear
      ribosomal DNA (rDNA) with greater than 1700 introns reported in these genes.
      These ribozymes generally spread through endonuclease-mediated intron homing.
      Another putative pathway is reverse splicing whereby a free group I intron
      inserts into a homologous or heterologous RNA through complementary base-pairing
      between the intron and exon RNA. Reverse-transcription of the RNA followed by
      general recombination results in intron spread. Here we used phylogenetics to
      test for reverse splicing spread in a taxonomically broadly sampled data set of
      fungal group I introns including 9 putatively ancient group I introns in the rDNA
      of the yeast-like symbiont Symbiotaphrina buchneri. RESULTS: Our analyses reveal
      a complex evolutionary history of the fungal introns with many cases of vertical
      inheritance (putatively for the 9 introns in S. buchneri) and intron lateral
      transfer. There are several examples in which introns, many of which are still
      present in S. buchneri, may have spread through reverse splicing into
      heterologous rDNA sites. If the S. buchneri introns are ancient as we postulate,
      then group I intron loss was widespread in fungal rDNA evolution. CONCLUSION: On
      the basis of these results, we suggest that the extensive distribution of fungal
      group I introns is at least partially explained by the reverse splicing movement
      of existing introns into ectopic rDNA sites.

PMID- 16300680
TI  - Protective effect of leptin against ischemia-reperfusion injury in the rat small
      intestine.
AB  - BACKGROUND: The small intestine is extremely sensitive to ischemia-reperfusion
      (I/R) injury and a range of microcirculatory disturbances which contribute to
      tissue damage. Previous studies have shown that leptin plays an important
      physiological role in the microvasculature. The aim of this study was to evaluate
      the protective effects of leptin in I/R--induced mucosal injury in the small
      intestine. METHODS: Forty rats were divided into 5 groups (n = 8). Group I was
      subjected to a sham operation. Following mesenteric ischemia in group II
      (control); physiologic saline 1 cm3, in group III; leptin 100 microg/kg, and
      physiologic saline 1 cm3, in group IV; NG-L-arginine methyl ester (L-NAME) 20
      mg/kg, and physiologic saline 1 cm3, in group V; leptin 100 microg/kg, L-NAME 20
      mg/kg, and physiologic saline 1 cm3 were given intra-peritoneally. In these
      groups, an I/R procedure was performed by occlusion of the superior mesenteric
      artery for 45 min followed by 120 min reperfusion. After reperfusion, the small
      intestines were resected for malondialdehyde (MDA) and nitric oxide (NO)
      concentration and histopathologic properties. Mucosal lesions were scored between
      0 and 5. Tissue MDA and NO concentration and histopathologic grades were compared
      statistically. RESULTS: Tissue MDA level significantly increased (P < 0.05),
      tissue NO level significantly decreased in group V animals, compared to group III
      animals respectively (P < 0.001). Histopathologically, intestinal injury
      significantly decreased in the leptin treated ischemic group. CONCLUSION: Leptin
      can be used safely in mesenteric occlusive diseases, since it induces NO
      formation and release in mesenteric vessels.

PMID- 16300681
TI  - Maximal COX-2 and ppRb expression in neurons occurs during early Braak stages
      prior to the maximal activation of astrocytes and microglia in Alzheimer's
      disease.
AB  - Neuronal expression of cyclooxygenase-2 (COX-2) and cell cycle proteins is
      suggested to contribute to neurodegeneration during Alzheimer's disease (AD). The
      stimulus that induces COX-2 and cell cycle protein expression in AD is still
      elusive. Activated glia cells are shown to secrete substances that can induce
      expression of COX-2 and cell cycle proteins in vitro. Using post mortem brain
      tissue we have investigated whether activation of microglia and astrocytes in AD
      brain can be correlated with the expression of COX-2 and phosphorylated
      retinoblastoma protein (ppRb). The highest levels of neuronal COX-2 and ppRb
      immunoreactivity are observed in the first stages of AD pathology (Braak 0-II,
      Braak A). No significant difference in COX-2 or ppRb neuronal immunoreactivity is
      observed between Braak stage 0 and later Braak stages for neurofibrillary changes
      or amyloid plaques. The mean number of COX-2 or ppRb immunoreactive neurons is
      significantly decreased in Braak stage C compared to Braak stage A for amyloid
      deposits. Immunoreactivity for glial markers KP1, CR3/43 and GFAP appears in the
      later Braak stages and is significantly increased in Braak stage V-VI compared to
      Braak stage 0 for neurofibrillary changes. In addition, a significant negative
      correlation is observed between the presence of KP1, CR3/43 and GFAP
      immunoreactivity and the presence of neuronal immunoreactivity for COX-2 and
      ppRb. These data show that maximal COX-2 and ppRb immunoreactivity in neurons
      occurs during early Braak stages prior to the maximal activation of astrocytes
      and microglia. In contrast to in vitro studies, post mortem data do not support a
      causal relation between the activation of microglia and astrocytes and the
      expression of neuronal COX-2 and ppRb in the pathological cascade of AD.

PMID- 16300682
TI  - Phosphoenolpyruvate carboxykinase and the critical role of cataplerosis in the
      control of hepatic metabolism.
AB  - BACKGROUND: The metabolic function of PEPCK-C is not fully understood; deletion
      of the gene for the enzyme in mice provides an opportunity to fully assess its
      function. METHODS: The gene for the cytosolic form of phosphoenolpyruvate
      carboxykinase (GTP) (EC 4.1.1.32) (PEPCK-C) was deleted in mice by homologous
      recombination (PEPCK-C-/- mice) and the metabolic consequences assessed. RESULTS:
      PEPCK-C-/- mice became severely hypoglycemic by day two after birth and then died
      with profound hypoglycemia (12 mg/dl). The mice had milk in their stomachs at day
      two after birth and the administration of glucose raised the concentration of
      blood glucose in the mice but did not result in an increased survival. PEPCK-C-/-
      mice have two to three times the hepatic triglyceride content as control
      littermates on the second day after birth. These mice also had an elevation of
      lactate (2.5 times), beta-hydroxybutyrate (3 times) and triglyceride (50%) in
      their blood, as compared to control animals. On day two after birth, alanine,
      glycine, glutamine, glutamate, aspartate and asparagine were elevated in the
      blood of the PEPCK-C-/- mice and the blood urea nitrogen concentration was
      increased by 2-fold. The rate of oxidation of [2-14C]-acetate, and [5-14C]
      glutamate to 14CO2 by liver slices from PEPCK-C-/- mice at two days of age was
      greatly reduced, as was the rate of fatty acid synthesis from acetate and
      glucose. As predicted by the lack of PEPCK-C, the concentration of malate in the
      livers of the PEPCK-C-/- mice was 10 times that of controls. CONCLUSION: We
      conclude that PEPCK-C is required not only for gluconeogenesis and
      glyceroneogenesis but also for cataplerosis (i.e. the removal of citric acid
      cycle anions) and that the failure of this process in the livers of PEPCK-C-/-
      mice results in a marked reduction in citric acid cycle flux and the shunting of
      hepatic lipid into triglyceride, resulting in a fatty liver.

PMID- 16300683
TI  - Opportunistic screening for iron-deficiency in 6-36 month old children presenting
      to the Paediatric Emergency Department.
AB  - BACKGROUND: The Complete Blood Count (CBC) is a test frequently performed on
      children presenting to the Pediatric Emergency Department (PED), usually for the
      evaluation of an infectious illness. The CBC also allows for screening for Iron
      deficiency Anemia. This study aims to determine the prevalence of a low Mean Cell
      Volume (MCV) in children having a CBC performed during a PED visit and whether
      physicians acted upon the abnormal value. METHODS: We present a retrospective
      cohort study. We reviewed the PED charts of all children 6-36 months of age who
      had a CBC performed during a 4-month period and the red blood cell mean cell
      volume was low. Our main outcome variable was whether or not the possible iron
      deficiency was addressed through documentation of either iron therapy or further
      investigation. RESULTS: 938 children had a CBC performed during the two periods.
      Of these, 78 (8%) had an abnormal MCV or Hemoglobin with no previously identified
      explanation. Physicians documented either treatment or follow-up investigations
      in 27 cases (35%, 95% CI: 24-46%). Factors associated with the physician
      documenting either treatment or investigation plan were the following: hemoglobin
      level (OR 12.6; 95%CI: 4.0, 39) and age < or = 18 months (OR 4.2; 95%CI: 1.4,
      13). CONCLUSION: Children who have had a CBC in the PED can be screened for iron
      deficiency at no additional cost. Physicians may be under-utilizing this
      information.

PMID- 16300684
TI  - Office bladder distention with electromotive drug administration (EMDA) is
      equivalent to distention under general anesthesia (GA).
AB  - BACKGROUND: Bladder distention is commonly used in diagnosis and treatment of
      interstitial cystitis (IC). Traditionally performed in the operating room under
      general or spinal anesthesia (GA), it is expensive and associated with short term
      morbidity. Office bladder distention using electromotive drug administration
      (EMDA) has been suggested as an alternative that is well tolerated by patients.
      We report the first comparative findings of patients undergoing both office
      distention with EMDA and distention in the operating room (OR) with GA. METHODS:
      This retrospective chart review identified 11 patients participating in two
      protocols of EMDA bladder distention who also underwent bladder distention under
      GA either prior to or after the EMDA procedure. RESULTS: The median absolute
      difference in bladder capacity between GA and EMDA was only 25 cc; the median
      percent difference was 5%. Cystoscopic findings, while not prospectively
      compiled, appear to have been similar. CONCLUSION: This study represents the
      first comparison between distention with EMDA versus GA and confirms the
      technical feasibility of performing bladder distention in an office setting. The
      distention capacity achieved in the office was nearly identical to that in the OR
      and the cystoscopic findings very similar. Further investigation into the
      comparative morbidity, cost, and other outcome measures is warranted to define
      the ultimate role of EMDA bladder distention in the clinical evaluation and care
      of patients with IC.

PMID- 16300686
TI  - Psychosocial and demographic factors associated with response to prophylactic
      lithium: a systematic review for bipolar disorders.
AB  - BACKGROUND: The aim was to systematically integrate the available evidence on
      psychosocial and demographic factors associated with response prediction to
      prophylactic lithium. METHOD: Each psychosocial or demographic variable that was
      related to lithium response in at least one study was examined with respect to
      response prediction. If several studies were located for the same variable
      results were integrated using a meta-analytical approach. To account for
      heterogeneity of primary studies aggregation of results was based on a random
      effects model. RESULTS: Out of 27 psychosocial and demographic variables
      investigated in this review, nine variables were identified as significantly
      related to outcome under to prophylactic lithium: (1) high social status, (2)
      social support, (3) good compliance, and (4) dominance may be protective against
      a recurrence under lithium. In contrast, (5) stress, (6) high expressed emotions,
      (7) neurotic personality traits, (8) unemployment, and (9) a high number of life
      events were identified as possible risk factors for poor response. CONCLUSIONS:
      This systematic review shows a surprisingly high number of psychosocial variables
      to be related to lithium response. Effect sizes were, however, small to moderate.
      Many variables should, therefore, be considered simultaneously to predict
      response.

PMID- 16300687
TI  - Internal source monitoring and communication disturbance in patients with
      schizophrenia.
AB  - BACKGROUND: This study examined the relationship between internal source
      monitoring and disordered speech in patients with schizophrenia or
      schizoaffective disorder. It was predicted that internal source monitoring would
      relate specifically to one type of communication disturbance, the missing
      information reference. METHOD: Immediate, working, and internal source memory
      were assessed in 47 out-patients diagnosed with schizophrenia or schizoaffective
      disorder. Speech samples were also collected from this sample and coded for six
      types of communication disturbance. RESULTS: Of the six types of communication
      disturbance coded in this study, internal source monitoring indices were uniquely
      related to the frequency of the missing information reference. Furthermore,
      internal source monitoring was the only type of short-term memory process
      assessed in this study that was related to the missing information reference.
      Neither immediate nor working-memory capacity was related significantly to the
      frequency of this type of communication disturbance. CONCLUSIONS: This study adds
      to our knowledge of the neurocognitive processes that underlie communication
      disturbance in the speech of patients with schizophrenia.

PMID- 16300688
TI  - Saccadic distractibility is elevated in schizophrenia patients, but not in their
      unaffected relatives.
AB  - BACKGROUND: Saccadic distractibility, as measured by the antisaccade task, has
      attracted attention as a putative endophenotypic marker for schizophrenia. Some
      studies have suggested that this measure is elevated in the unaffected relatives
      of schizophrenia patients. However, recent studies have called this into question
      and the topic remains controversial. METHOD: Saccadic distractibility was
      measured in 53 patients with DSM-IV schizophrenia, 80 unaffected first-degree
      relatives and 41 unaffected controls.Results. Schizophrenia patients performed
      worse than relatives and controls combined (p<0.00001), but relatives did not
      differ significantly from controls. Performance in multiply affected families was
      no worse than that in singly affected families. Relatives with a high presumed
      genetic risk for schizophrenia performed no worse than other relatives. The
      performance of the patients did not predict that of their relatives. CONCLUSIONS:
      These results demonstrate that saccadic distractibility is strongly associated
      with disease status but not with genetic loading for schizophrenia. We conclude
      that saccadic distractibility is unlikely to be useful as an endophenotypic
      marker in schizophrenia.

PMID- 16300689
TI  - Normal levels of prepulse inhibition in the euthymic phase of bipolar disorder.
AB  - BACKGROUND: Deficits in prepulse inhibition (PPI) of the acoustic startle
      response have been suggested as a potentially useful endophenotype for
      schizophrenia spectrum disorders and may explain certain symptoms and cognitive
      deficits observed in the psychoses. PPI deficits have also been found in mania,
      but it remains to be confirmed whether this dysfunction is present in the
      euthymic phase of bipolar disorder. METHOD: Twenty-three adult patients with DSM
      IV bipolar disorder were compared to 20 controls on tests of acoustic startle
      reactivity and PPI of the startle response. Sociodemographic and treatment
      variables were recorded and symptom scores assessed using the Hamilton Depression
      Inventory and the Young Mania Rating Scale. RESULTS: Overall, the patient and
      control groups demonstrated similar levels of startle reactivity and PPI,
      although there was a trend for the inter-stimulus interval to differentially
      affect levels of PPI in the two groups. CONCLUSIONS: In contrast to bipolar
      patients experiencing a manic episode, general levels of PPI were normal in this
      euthymic sample. Further studies are required to confirm this finding and to
      determine the mechanisms by which this potential disruption/normalization occurs.
      It is suggested that an examination of PPI in a high-risk group is required to
      fully discount dysfunctional PPI as a potentially useful endophenotype for
      bipolar disorder.

PMID- 16300690
TI  - Should excessive worry be required for a diagnosis of generalized anxiety
      disorder? Results from the US National Comorbidity Survey Replication.
AB  - BACKGROUND: Excessive worry is required by DSM-IV, but not ICD-10, for a
      diagnosis of generalized anxiety disorder (GAD). No large-scale epidemiological
      study has ever examined the implications of this requirement for estimates of
      prevalence, severity, or correlates of GAD. METHOD: Data were analyzed from the
      US National Comorbidity Survey Replication, a nationally representative, face-to
      face survey of adults in the USA household population that was fielded in 2001
      2003. DSM-IV GAD was assessed with Version 3.0 of the WHO Composite International
      Diagnostic Interview. Non-excessive worriers meeting all other DSM-IV criteria
      for GAD were compared with respondents who met full GAD criteria as well as with
      other survey respondents to consider the implications of removing the
      excessiveness requirement. RESULTS: The estimated lifetime prevalence of GAD
      increases by approximately 40% when the excessiveness requirement is removed.
      Excessive GAD begins earlier in life, has a more chronic course, and is
      associated with greater symptom severity and psychiatric co-morbidity than non
      excessive GAD. However, non-excessive cases nonetheless evidence substantial
      persistence and impairment of GAD, high rates of treatment-seeking, and
      significantly elevated co-morbidity compared with respondents without GAD. Non
      excessive cases also have sociodemographic characteristics and familial
      aggregation of GAD comparable to excessive cases. CONCLUSIONS: Individuals who
      meet all criteria for GAD other than excessiveness have a somewhat milder
      presentation than those with excessive worry, yet resemble excessive worriers in
      a number of important ways. These findings challenge the validity of the
      excessiveness requirement and highlight the need for further research into the
      optimal definition of GAD.

PMID- 16300691
TI  - Prevalence, service use, and demographic correlates of 12-month DSM-IV
      psychiatric disorders in Mexico: results from the Mexican National Comorbidity
      Survey.
AB  - BACKGROUND: This paper describes the 12-month prevalence, severity and
      demographic correlates of 16 DSM-IV psychiatric disorders and service utilization
      in the Mexican urban population aged 18-65 years of age. This is representative
      of 75% of the national adult population. METHOD: The sample design was a strict
      probability selection scheme. The response rate was 76.6%. The World Mental
      Health Survey version of the Composite International Diagnostic Interview was
      installed on laptops and administered by lay interviewers. An international WHO
      task force carried out its translation into Spanish. RESULTS: The 12-month
      prevalence of any disorder was 12.1%. The most common disorders were specific
      phobia (4.0%), major depressive disorder (3.7%) and alcohol abuse or dependence
      (2.2%). The 12-month prevalence of very severe disorders was 3.7% of which only
      24% used any services. Age was the only variable associated with any 12-month
      disorder, with the younger more likely to report any disorder. Income was
      associated with severity, with low and low-average incomes more likely to report
      a 12-month disorder. Females were more likely to report a mood and anxiety
      disorder, but less likely to report a substance disorder. The group of
      separated/widowed/divorced was more likely to report a mood and an impulse
      control disorder. CONCLUSIONS: The results show that while psychiatric disorders
      are common in the Mexican population, very severe mental disorders are less
      common and there is extreme under-utilization of mental health services.

PMID- 16300692
TI  - The relationship between post-traumatic stress disorder, depression and
      cardiovascular disease in an American Indian tribe.
AB  - BACKGROUND: Empirical findings suggest that psychiatric illness is associated
      with cardiovascular disease (CVD). The purpose of this study was to compare the
      strength of the association of lifetime post-traumatic stress disorder (PTSD) and
      lifetime major depression on CVD among Northern Plains American Indians. METHOD:
      A total of 1414 participants aged 18-57 years completed a structured interview
      that assessed psychiatric diagnoses, alcohol abuse/dependence, self-reported CVD,
      and traditional CVD risk factors including age, sex, education, diabetes, high
      blood pressure, and smoking. Logistic regression analyses compared the odds
      ratios of CVD in participants with and without diagnosed PTSD or major
      depression. RESULTS: The rates of lifetime PTSD and major depression were 15% and
      8% respectively. CVD was more commonly reported by participants with PTSD than by
      those without PTSD (12% v. 5%, p<or=0.01). Likewise, more participants with major
      depression reported CVD than did their non-depressed counterparts (14% v. 6%,
      p<or=0.05). PTSD was significantly associated with CVD even after controlling for
      traditional CVD risk factors and major depression (odds ratio 2.0, confidence
      interval 1.1-3.8). In contrast, the association of major depression with CVD was
      not significant after accounting for both traditional risk factors and PTSD.
      CONCLUSIONS: Rates of PTSD are high in American Indian communities. Rising CVD
      rates in this population may be better understood if PTSD is considered along
      with other traditional risk factors. Future research should examine the
      association and mechanisms of PTSD and CVD prospectively. Such data could lead to
      more effective CVD prevention efforts for American Indians.

PMID- 16300693
TI  - Immigrants from the former Soviet Union, 5 years post-immigration to Israel:
      adaptation and risk factors for psychological distress.
AB  - BACKGROUND: Studies about the effect of time on the degree of psychological
      distress among immigrants have reported conflicting findings. We investigated
      this issue in Israel, which supports actively the absorption of immigrants, and
      also looked for risk and protective factors for psychological distress 5 years
      post-immigration. METHOD: A nationwide sample of 600 subjects who emigrated from
      the former Soviet Union to Israel in 1990 were interviewed in 1995, with the
      demoralization subscale of the Psychiatric Epidemiologic Research Interview (PERI
      D) for psychological distress, and with a series of questions regarding
      sociodemographic characteristics, personal assets and their absorption
      experience. The results were compared with those obtained in a previous study for
      a sample of the same cohort of immigrants in their first year post-immigration. A
      multivariate analysis was carried out to examine the relation between the PERI
      score and the different independent variables. RESULTS: Although, 5 years after
      immigration, a favorable change in objective parameters of absorption was found,
      no decrease in psychological distress was observed. The main risk factors
      remaining significantly associated with psychological distress in the final model
      were: adverse life events, lack of perceived social support, poor family
      functioning, external locus of control, poor physical health status, non
      identification with host society and, to a lesser degree, poor material
      conditions. CONCLUSION: Psychological readjustment apparently takes longer than
      other processes of adaptation. Several years after immigration, social and
      psychological factors have a more important role for the well-being of immigrants
      than their material conditions.

PMID- 16300694
TI  - Psychiatric disorder in the children of antisocial parents.
AB  - BACKGROUND: Although parents with psychiatric disorders are likely to have
      children with psychiatric problems, the nature of disorder risk to offspring of
      antisocial parents has received limited attention. METHOD: We examined the
      prevalence of common externalizing and internalizing disorders in the pre
      adolescent and late adolescent offspring of antisocial parents. Lifetime
      diagnoses for a sample of 11-year-old twins (958 males, 1042 females) and a
      sample of 17-year-old twins (1332 males, 1434 females), as well as their parents,
      were obtained through in-person interviews. Odds ratios were calculated for the
      effect of the parent's diagnosis on the child's diagnosis, controlling for the
      effect of the co-parent's diagnosis.Results. We found that parental antisociality
      places the child at increased risk for developing a range of externalizing and
      internalizing disorders. This increase is evident by pre-adolescence and extends
      to a wide range of disorders by late adolescence. Each parent has an effect net
      any effects of the co-parent. CONCLUSIONS: Antisocial parents have children who
      have an increased likelihood of developing a broad range of psychiatric
      disorders.

PMID- 16300695
TI  - Internalizing and externalizing problems in adolescence: general and dimension
      specific effects of familial loadings and preadolescent temperament traits.
AB  - BACKGROUND: We investigated the links between familial loading, preadolescent
      temperament, and internalizing and externalizing problems in adolescence, hereby
      distinguishing effects on maladjustment in general versus dimension-specific
      effects on either internalizing or externalizing problems. METHOD: In a
      population-based sample of 2230 preadolescents (10-11 years) familial loading
      (parental lifetime psychopathology) and offspring temperament were assessed at
      baseline by parent report, and offspring psychopathology at 2.5-years follow-up
      by self-report, teacher report and parent report. We used purified measures of
      temperament and psychopathology and partialled out shared variance between
      internalizing and externalizing problems. RESULTS: Familial loading of
      internalizing psychopathology predicted offspring internalizing but not
      externalizing problems, whereas familial loading of externalizing psychopathology
      predicted offspring externalizing but not internalizing problems. Both familial
      loadings were associated with Frustration, low Effortful Control, and Fear.
      Frustration acted as a general risk factor predicting severity of maladjustment;
      low Effortful Control and Fear acted as dimension-specific risk factors that
      predicted a particular type of psychopathology; whereas Shyness, High-Intensity
      Pleasure, and Affiliation acted as direction markers that steered the conditional
      probability of internalizing versus externalizing problems, in the event of
      maladjustment. Temperament traits mediated one-third of the association between
      familial loading and psychopathology. Findings were robust across different
      composite measures of psychopathology, and applied to girls as well as boys.
      CONCLUSIONS: With regard to familial loading and temperament, it is important to
      distinguish general risk factors (Frustration) from dimension-specific risk
      factors (familial loadings, Effortful Control, Fear), and direction markers that
      act as pathoplastic factors (Shyness, High-Intensity Pleasure, Affiliation) from
      both types of risk factors. About one-third of familial loading effects on
      psychopathology in early adolescence are mediated by temperament.

PMID- 16300696
TI  - Nalbuphine prevents haemodynamic response to endotracheal intubation.
AB  - OBJECTIVE: To determine the efficacy of nalbuphine in preventing the increase in
      heart rate and mean arterial pressure in response to laryngoscopy and orotracheal
      intubation. DESIGN: A comparative trial. PLACE AND DURATION OF STUDY: Department
      of Anaesthesia, Pakistan Naval Hospital Shifa, Karachi, Pakistan, from January
      2001 to January 2002. PATIENTS AND METHODS: Forty healthy patients having general
      anaesthesia for elective surgery, were selected by convenient sampling to receive
      either saline [group I (control group); n= 20] or nalbuphine 0.2 mg/kg; (group
      II; n = 20) as a bolus dose, 5 minutes before laryngoscopy. Double blinding was
      done as the patient as well as the researcher was not aware of which study drug
      was being given. Heart rate (HR) and mean arterial pressure (MAP) were measured
      before induction of anaesthesia (time 1), just after intubation (time 2), then
      after every minute upto 5 minutes (time 3-7) and after 10 minutes of intubation
      (time 8). Twenty percent rise in heart rate (HR) and mean arterial pressure (MAP)
      was considered as significant. Data were analyzed by using SPSS version 10.
      Student's t-test was used for the significance of parameters at p < 0.05 and
      analysis of variance test (ANOVA) was interpreted for group analysis of the
      parameters. RESULTS: There was a significant increase (p <0.05) in heart rate
      (53.4%) in group I after intubation at time 2 compared with baseline at time 1,
      as compared to group II (15.5%). The HR gradually decreased during time 3 to 8
      but still remained slightly higher than group II. MAP also increased
      significantly (p <0.05) in group I, at time 2 (43.6%) compared with baseline at
      time 1 as compared to group II (10.5%). The MAP also gradually decreased during
      time 3 to 8 but remained on slightly higher level than group II. CONCLUSION:
      Nalbuphine 0.2 mg/kg prevented a marked rise in heart rate and mean arterial
      pressure associated with laryngoscopy and orotracheal intubation.

PMID- 16300697
TI  - Relationship of serum and seminal plasma zinc levels and serum testosterone in
      oligospermic and azoospermic infertile men.
AB  - OBJECTIVE: To measure the zinc level in fertile and infertile population and to
      find out relationship of serum and seminal plasma zinc levels and serum
      testosterone in oligospermic and azoospermic infertile men. DESIGN: Comparative
      study. PLACE AND DURATION OF STUDY: The Infertility Clinic, Jinnah Postgraduate
      Medical Center (JPMC), Karachi, from January 2002-July 2003. PATIENTS AND
      METHODS: Fifty-eight primary infertile male subjects, without any treatment, who
      had regular unprotected intercourse for at least 12 months without conception
      with their partners, aged 20-40 years, having normal and regular menstrual cycles
      without any uterine pathology or hormonal disturbance were selected from
      Infertile Clinic, Jinnah Postgraduate Medical Center, Karachi. After semen
      analyses, they were grouped as, oligospermic (30), and azoospermic (28).
      Twentyfive known fertile male selected from general population (their spouse had
      given birth to a child within one year) and after semen analysis were taken as
      normospermic control group . Semen analyzed according to WHO criteria and serum
      and seminal plasma zinc was estimated by 5Br. PAPS colorimetric method. Serum
      testosterone, LH, and FSH were measured by ELISA, using kits supplied by
      Diagnostic System Laboratories (DSL), U.S.A. RESULTS: The mean value for
      testosterone was significantly low in oligospermic, (8.04 -/+ 0.76) and
      azoospermic subjects (7.14 -/+ 0.27) as compared to normospermic (9.90 -/+ 0.14)
      control groups (p<0.05, p<0.001 respectively), serum LH (p<0.05, p<0.001
      respectively) and FSH (p<0.05) were significantly higher than normospermic
      control group. Serum and seminal plasma zinc levels was low in oligospermic, and
      azoospermic subjects when compared with normospermic control groups (p<0.05,
      p<0.001 respectively). This suggests its involvement in spermatogenesis and
      infertility in such patients. Seminal zinc level has weak correlation with
      testosterone in oligospermic (r=0.44, p<0.05) and with serum zinc in azoospermic
      subjects (r=0.49, p<0.05) while no correlation was observed with LH and FSH in
      all the groups. CONCLUSION: In this study, there was significant decrease in
      serum and seminal plasma zinc levels in oligospermic and azoospermic infertile
      males with significantly low androgen. It indicates zinc has a possible role for
      spermatogenesis and steroidogenesis. Therefore, zinc concentration in seminal
      plasma should be considered as one of the factors responsible for decreased
      testicular function in infertile male subjects.

PMID- 16300698
TI  - Increases in brain tryptophan concentration in stressed rats following ethanol
      administration.
AB  - OBJECTIVE: To determine the effect of acute ethanol administration on tryptophan
      metabolism in stressed and unstressed rats. DESIGN: Phase I clinical trial. PLACE
      AND DURATION OF STUDY: Department of Biochemistry, University of Karachi. The
      investigation was carried out in the year 2004. SUBJECTS AND METHODS: Male Albino
      Wistar rats (150-200 gm body wt) were selected and divided into four groups (n=5,
      in each group). Rats were injected either saline or 5% (v/v) ethanol (i.p) and
      were immediately subjected to 2 hours immobilization stress while respective
      control (non immobilized) groups remained in their home cages. RESULTS: There was
      no effect of 2 hours immobilization stress in male rats on peripheral liver
      tryptophan (Tp) metabolism, but brain Tp, 5-hydroxytryptamine (5-HT) and 5
      hydroxyindole acetic acid (5-HIAA) concentrations were increased by 71.6%
      (P<0.01), 80.4% (P<0.01) and 179% (P<0.01) respectively. Two hours immobilization
      stress immediately after ethanol (5% v/v, 2 ml/kg) administration in rats
      increases holo and total tryptophan pyrrolase enzyme activities by 276% (P<0.01)
      and 129% (P<0.01) in ethanol injected stressed rats when compared with ethanol
      injected unstressed rats. Holo enzyme was increased by 60.7% but apoenzyme was
      decreased by 41% in ethanol injected stressed rats when compared with similarly
      treated saline injected stressed rats. Liver and serum total tryptophan
      concentrations were decreased by 25.7% (P<0.05) and 45.6% (P<0.01) respectively.
      Brain Tp and 5-HIAA concentrations were increased by 176% (P<0.01) and 168%
      (P<0.01) respectively. In ethanol injected unstressed group of rats holo and
      total enzyme activities were inhibited by 65% (P<0.01) and 53.1% (P<0.01)
      respectively leading to increase in liver Tp concentrations by 75.4% (P<0.01).
      Serum total Tp concentration was decreased by 64.4% (P<0.01). Brain Tp and 5-HIAA
      concentrations were not effected by ethanol injected unstress rats but 5-HT
      concentrations were increased by 75.8% (P<0.01) when compared with saline
      injected unstressed rats. CONCLUSION: It was found that increases in brain Tp
      concentrations were greater in ethanol injected stressed rats than in saline
      injected stressed group of rats when compared with their respective controls.
      Conditioned stress and ethanol both increase brain 5-HT concentrations when
      compared to saline treated unstressed controls.

PMID- 16300699
TI  - Disaster psychiatry: need for appraisal.

PMID- 16300700
TI  - Oral candidal species among smokers and non-smokers.
AB  - OBJECTIVE: To determine the various oral Candidal species among healthy Malaysian
      adults. DESIGN: Case-control study. PLACE AND DURATION OF STUDY: This study was
      collaborated between the Department of Medical Microbiology, Faculty of Medicine
      and Department of Oral Pathology, Oral Medicine and Periodontology, Faculty of
      Dentistry, University of Malaya, Kuala Lumpur, Malaysia, between September 2002
      till January 2004. PATIENTS AND METHODS: One hundred adults (50 smokers and 50
      non-smokers), aged between 40 and 70 years were studied. Swabs and carbohydrate
      assimilation (Saboraud Dextrose Agar, Corn Meal Agar, API 20C AUX System) were
      performed. Specimens were collected from dorsum of the tongue, buccal mucosa and
      commissures (right and left each). Colony forms were established by positive
      colony forming units, on SDA medium (24-48 hours). Germ tube test for
      (true/pseudohyphae) growth was done on Corn Meal Agar Medium. Candida biotypes
      were evaluated by API 20C AUX system, which had a numerical 7 digit profile,
      added to evaluate a definite Candida species. RESULTS: Thirty-five percent of
      Malaysian adults harbored Candida intraorally. Candidal species identified among
      100 subjects had C. albicans (27) 77%, C. glabrata (3) 8%, C. famata, C.
      tropicalis, C. krusei, C. lusitaniae and C. guilliermondii (1) 3% each. Thirty
      three positive cases comprised of 35 species i.e. two cases had two species each.
      Fifty seven percent of these were smokers and 43% non-smokers. These included 40%
      Chinese, 36% Malays and 24% Indians. Species were, however, not specified
      according to intra-oral sites i.e. buccal, commissural mucosa and dorsum of
      tongue. CONCLUSION: On this series C. albicans is the most common species found
      in the oral cavity of Malaysian adults. It is equally frequent in smokers and non
      smokers, but showed a predilection for the ethnic Chinese group.

PMID- 16300701
TI  - The efficacy of local infiltration of triamcinolone acetonide with lignocaine
      compared with lignocaine alone in the treatment of postherpetic neuralgia.
AB  - OBJECTIVE: To assess the efficacy of local infiltration of corticosteroid with
      lignocaine compared to lignocaine alone in the treatment of postherpetic
      neuralgia. DESIGN: A randomized clinical trial. PLACE AND DURATION OF STUDY: The
      Skin Department, Military Hospital, Rawalpindi from September 2002 to March 2003.
      PATIENTS AND METHODS: Sixty patients were selected for the study. They were
      randomly assigned to two groups. Group-I received injection triamcinolone
      acetonide with lignocaine and group-II was given injection lignocaine alone.
      Three injections were given to each patient at fortnightly interval and pain
      relief was assessed by visual analogue scale at 6 and 12 weeks following the
      first injection. RESULTS: Follow-up at 6 weeks showed complete pain relief in
      63.3% (n=19) patients of group-I in comparison to 16.6% (n=5) of group-II. Chi
      square value was 13.3 (p<0.001). At 12 weeks follow-up group-I showed further
      improvement with complete pain relief in 83.3% (n=25) whereas group-II showed
      diminishing response with cure rates falling to 6.6% (n=2). Chi-square value was
      35.6 (p<0.001). CONCLUSION: Locally infiltrated injection triamcinolone acetonide
      with lignocaine was significantly more effective than injection lignocaine alone
      in the treatment of postherpetic neuralgia both at 6 and 12 weeks follow-up.

PMID- 16300702
TI  - Prediction of benignity or malignancy of a lesion using BI-RADS.
AB  - OBJECTIVE: To determine the Positive Predictive Value (PPV) of the Breast Imaging
      Reporting and Data System (BI-RADS) categories as confirmed by histopathology of
      localized lesion. DESIGN: An observational study. PLACE AND DURATION OF STUDY:
      All patients undergoing mammographic needle localizations for breast lesions from
      January 2001 to December 2003 were included in the study. The study was conducted
      at the Radiology Department of Aga Khan University Hospital, Karachi. PATIENTS
      AND METHODS: The medical records of all patients undergoing needle localization
      during the study period were retrospectively reviewed. In a total of 111
      patients, 114 mammographically-guided needle localizations were performed for
      breast lesions. In all these patients the mammographic finding and BI-RADS
      category were recorded. Statistical analysis was done on SPSS. Histopathological
      results of the localized sample were used as a gold standard to calculate the
      PPV. The PPV for each assessment category was calculated by dividing the number
      of patients positive for malignancy on histopathological examination by the total
      number of patients who underwent biopsy for each BI-RADS assessment category.
      RESULTS: In 114 localizations the histopathologic finding showed 25 (22%) cancers
      (10 [40%] were ductal carcinoma in situ (DCIS); (15 [60 %] were invasive cancers)
      and 89 (78 %) benign lesions. All the mammographic lesions were categorized as, 7
      (6%) category 0 lesions; 3 (2%) category 1 lesions, and 30 (26%) category 2
      lesions; the PPV was 0% for category 0,1,2 (0% of 7,3,30 lesions respectively).
      There were 18 (16 %) category 3 lesions; the PPV was 5% (1 of 18 lesions). One
      case of cancer in this group was DCIS. There were 50 (44%) category 4 lesions;
      the PPV was 34% (17 of 50 lesions). There were 6 (5%) category 5 lesions; the PPV
      was 83% (5 of 6 lesions). CONCLUSION: The number of biopsies performed for benign
      lesion can be reduced by using BI-RADS categories, as it has a good PPV.

PMID- 16300703
TI  - Healing during physician-patient consultation.
AB  - OBJECTIVE: To determine the patient perceptions regarding healing during a
      physician-patient consultation. DESIGN: A questionnaire-based survey. PLACE AND
      DURATION OF STUDY: Family Practice Center of the Aga Khan University Hospital,
      Karachi, Pakistan, in June 2004. PATIENTS AND METHODS: A questionnaire was
      designed that included the demographic profile of patients comprising age,
      gender, education and occupation as well as questions in line with the study
      objective. It was administered to 111 patients, visiting outpatient department of
      the hospital. Participants were explained the study objective, a written consent
      was taken and full confidentiality was assured. RESULTS: The mean age of the
      study population was 27.86 years. Majority of the subjects were males with 68%
      having graduate or more education. A physician-patient consultation has healing
      properties for patients and physicians, according to 99 (89%) and 67 (65%)
      respondents respectively, with 65 (58%) having had experienced healing during the
      consultation process. The competence of a physician, individual attention given
      by a physician and a cool and calm attitude of a physician, were reported to
      increase healing in a physician-patient consultation according to 34 (30%), 32
      (29%) and 13 (11%) respondents respectively. The unhelpful physician behavior,
      incorrect diagnosis and physician's rude and arrogant attitude were reported to
      decrease healing according to 42 (37%), 15 (14%) and 14 (13%) respondents
      respectively. CONCLUSION: The study shows that a majority of the patients believe
      a physician-patient consultation has healing properties on its own, based on
      healing potential in the consultation process itself. Physicians must try to find
      ways to improve their ability to act as healers during consultation with
      patients.

PMID- 16300704
TI  - Predictive power of Mannheim Peritonitis Index.
AB  - OBJECTIVE: To evaluate Mannheim Peritonitis Index (MPI) in predicting outcome in
      patients with secondary peritonitis and to assess each risk factor independently
      regarding its contribution towards final outcome. DESIGN: Prospective analytical
      study. PLACE AND DURATION OF STUDY: Surgical Unit-II of Rawalpindi General
      Hospital, from December 1999 to January 2001. PATIENTS AND METHODS: One hundred
      and twenty-six patients who presented to the department with secondary
      peritonitis were included in the study. MPI score was calculated for each patient
      on a pre-designed proforma and the patients were followed-up till death or
      discharged from the hospital. Death was the main outcome measure against which
      the MPI scores were analyzed under two categories; (i) score > or = 26 and < 26
      (ii) scores < 21, 2-29, and > 29. Data was analyzed on software SPSS (version
      11.0). Chi-square test was used to assess any significant association between
      scores and outcome. Odds ratios were calculated for individual risk factors.
      RESULTS: Mortality rate for MPI score > or = 26 was 28.1% while for scores less
      than 26 it was 4.3%. For MPI scores pound 20 mortality rate was 1.9%, for scores
      21-29 it was 21.9% and for score 30 or more it was 28.1%. Chi-square showed
      significant association between mortality and increasing MPI score (p < 0.01).
      Odd ratios calculated were significant for age > 50 years, malignancy, organ
      failure, pre-operative duration of peritonitis > 24 hours and cloudy, purulent
      exudate. CONCLUSION: Increasing MPI score is strongly associated with outcome in
      secondary peritonitis.

PMID- 16300705
TI  - Accuracy of sentinel lymph node biopsy for the assessment of axillary status in
      patients with early (T1) breast carcinoma.
AB  - OBJECTIVE: To determine the accuracy of SLN biopsy for the assessment of axillary
      status, and prognostic markers leading to lymphatic metastasis in patients with
      early (T1) breast cancer. DESIGN: Cross-sectional study. PLACE AND DURATION OF
      STUDY: Department of Surgery, Teaching and Research Hospital. Between January
      2000 and August 2004. PATIENTS AND METHODS: SLN mapping by blue dye method was
      performed on 39 patients with T1 breast carcinoma. SLNs, level 1 and 2 axillary
      nodes were dissected and excised. The size, pathologic features of the primary
      tumor, SLNs and other axillary nodes, and hormone receptors were evaluated by
      histopathologic examination. The rate of SLNs and non-SLNs involvement, and
      demographic, clinical and pathologic risk factors leading to nodal metastasis
      were established. The diagnostic accuracy of SLN for axillary status was
      calculated. RESULTS: SLNs were identified in 37 (95%) patients. The axilla had
      metastasis in 11 (28%) patients. Malignant cells involved SLNs in 8 patients. Non
      SLNs had metastasis in 3 patients without SLN involvement. The sensitivity,
      specificity and accuracy of SLN biopsy for predicting axillary status was
      calculated as 73%, 100% and 92% respectively. Four of 5 patients with non-SLN
      metastasis were pre-menopausal (p=0.03), and hormone receptor negative (p=0.04).
      All 5 patients had T1c tumors (p=0.14) and lymphovascular invasion (p=0.0004).
      CONCLUSION: SLN biopsy with high diagnostic accuracy may prevent unnecessary
      dissection of the axilla in the majority of patients with early (T1) breast
      carcinoma. Some risk factors as pre-menopausal status, absence of hormone
      receptors, and presence of lymphovascular invasion must be taken into account as
      important determinant of non-SLNs metastasis.

PMID- 16300706
TI  - Precut papillotomy outcome.
AB  - OBJECTIVE: To determine the success and complications of precut papillotomy using
      needle knife technique in common bile duct cannulation. DESIGN: Quasi
      interventional. PLACE AND DURATION OF STUDY: The Department of Gastroenterology
      and Hepatology, Federal Postgraduate Medical Institute, Sheikh Zayed Hospital,
      Lahore from April 2001 to August 2003. MATERIALS AND METHODS: From April 2001 to
      August 2003, a total of 347 ERCPs were performed at our institution. During this
      period, precut papillotomy was carried out in 79 patients. The data of these
      patients was evaluated for the success of the procedure and occurrence of short
      term complications. Other parameters such as age and gender of patients,
      appearance of ampulla, and the diagnoses were also recorded. RESULTS: Forty-five
      patients were women and 34 men. The mean age was 52 years (range 12-80 years).
      Precut helped to cannulate common bile duct in 67 patients at first attempt and
      in further 5 patients at second attempt with an overall success rate of 91.14%.
      Complications occurred in 8 (10.1%) patients. These include hemorrhage in 5
      (6.3%) patients and pancreatitis in 3 (3.8%). All complications were managed
      conservatively. CONCLUSION: Precut papillotomy is an effective technique in
      cannulating common bile duct in difficult cases with margin of safety, dependent
      on expertise.

PMID- 16300707
TI  - Prognostic factors in typhoid perforation.
AB  - OBJECTIVE: To discuss the effect of duration of illness before perforation and
      time interval between perforation and surgery on the prognosis of typhoid
      perforation. DESIGN: Comparative study. PLACE AND DURATION OF STUDY: Nishtar
      Hospital, Multan from September 2002 to September 2004. PATIENTS AND METHODS:
      Seventy-two patients of typhoid perforation were included in this study. The
      patients were divided into three groups A, B and C according to duration of
      illness before perforation. In these groups, typhoid perforation occurred during
      1st, 2nd and 3rd week respectively. Further patients were divided into group D, E
      and F according to time interval between perforation and surgery. In these groups
      surgery was carried out within 24 hours, 24-48 hours and after 48 hours
      respectively. RESULTS: Fifty-six patients were males and 16 were females. In
      groups A, B and C, mortality rate was 6.6%, 13.3% and 25%, while morbidity rate
      was 33.3%, 55.5% and 75% respectively. There were 12, 42 and 18 patients in Group
      D, E and F with mortality rate of 8.33%, 11.9% and 22.2% respectively. Group D
      had 41.6% morbidity rate while group E and F had 71.42% and 77.7% respectively.
      CONCLUSION: In this study, early perforation during the typhoid fever and short
      perforation-operation interval were good prognostic signs. So best results can be
      achieved by early patient's presentation and early operation.

PMID- 16300708
TI  - Early complications following pancreatico-duodenectomy.
AB  - OBJECTIVE: To determine the mortality and morbidity in patients after Whipple's
      pancreaticoduodenectomy. DESIGN: Descriptive study. PLACE AND DURATION OF STUDY:
      Department of General Surgery (Ward-2), Jinnah Postgraduate Medical Centre,
      Karachi. PATIENTS AND METHODS: All the patients who underwent standard Whipple's
      procedure were followed up during their hospital stay for early postoperative
      complication. The indicators for the development of complications included daily
      nasogastric (NG) tube output for delayed gastric emptying, ultrasound abdomen for
      intra-abdominal collections, presence of blood in drains and NG tubes for
      haemorrhage and measuring serum amylase for pancreatitis. RESULTS: Out of 30
      patients, 3 patients died in early postoperative period with 10% mortality while
      26.67% had wound infection, 16.67% had chest complications, 13.34% developed
      intra-abdominal collections, 10% had haemorrhage, 3.34% had delayed gastric
      emptying, 3.34% had pancreatic fistula and 3.34% had organ failure. CONCLUSION:
      In this series the procedure was associated with decreased mortality due to
      increased experience and skills but morbidity was still high due to lack of
      facilities for the detection and management of postoperative complications. It
      should only be performed in tertiary care centres with expert surgical teams and
      facilities for adequate management of postoperative complications.

PMID- 16300709
TI  - Impact of metformin therapy in patients with polycystic ovarian syndrome.
AB  - OBJECTIVE: To determine the effect of metformin therapy in achieving menstrual
      regularity, pregnancy, reducing obesity and hyperinsulinemia in patients with
      polycystic ovarian syndrome (PCOS). DESIGN: Interventional, quasi-experimental
      study. PLACE AND DURATION OF STUDY: Civil Hospital, Karachi from January 2002 to
      December 2003. PATIENTS AND METHODS: Thirty patients with PCOS diagnosed on
      clinical symptoms, ultrasound examination and hormonal assays were selected. All
      patients either had raised serum fasting insulin levels or fasting blood
      sugar/serum fasting insulin ratio of < 4:5. Patients were then given treatment
      with Metformin 500 mg TID and continued for six months. The patients were called
      back for follow-up on monthly basis and clinical and bio-chemical variables were
      recorded on a proforma at 3 months and 6 months of initiating metformin
      treatment. The chi-square test was done and p-value determined to assess the
      outcome. RESULTS: Significant effect of metformin therapy was observed at 3
      months follow-up visit, 5 (16.7%) women achieved pregnancy while 20 (66.6%) women
      had a regular menstrual cycle (p = 0.001), and a significant reduction in weight
      (67.4 vs. 65.4, p = 0.001) and hyperinsulinemia (FBS: FI = 3.34 vs. 6.63, p =
      0.001) was noted. After 6 months follow-up visit, 25 women were examined. Of
      these, 7 (28%) achieved pregnancy while 16 (64%) had regular menstrual cycle (p =
      0.001) and a significant reduction in weight and hyperinsulinemia (p = 0.001).
      CONCLUSION: Metformin is very effective in achieving menstrual regularity,
      ovulation and pregnancy in patients with polycystic ovarian syndrome.

PMID- 16300710
TI  - Frequency of hepatitis C in pregnancy and pregnancy outcome.
AB  - OBJECTIVE: To determine the frequency of HCV infections in pregnant women, to
      find out the risk factors for HCV infection in pregnant women and to compare
      pregnancy outcome of the sero-positive women with sero-negative women. DESIGN:
      Case-control study. PLACE AND DURATION OF STUDY: Shifa International Hospital,
      Islamabad, from June 2001 to May 2002. PATIENTS AND METHODS: Study was conducted
      on 947 booked pregnant women who were screened for HCV antibodies during
      antenatal consultation and were admitted for delivery in labour room. At the time
      of admission in labour ward, medical records of all patients were reviewed for
      anti HCV antibody testing and the presence of risk factors for HCV infection.
      Previous vaginal deliveries with episiotomy, previous surgeries, blood
      transfusions, and D&C for abortion or dysfunctional uterine bleeding were taken
      as independent variables. The obstetric outcome variables studied were: completed
      weeks of gestation by mother, birth weight and apgar score of newborns. The risk
      factors under study and the outcome variables were compared among HCV positive
      and negative women through a case-control study and measures of association
      calculated. RESULTS: The proportion of HCV sero-positivity among pregnant woman
      in our study was 3.27%. Among all the risk factors under study, previous surgery
      was found to have a significant association with HCV positive status of women
      (p=0.001). Other variables did not have significant association with HCV positive
      status in our study. There was no statistical difference in the mean birth weight
      of newborns (p= 0.94), mean Apgar score of newborns (p= 0.73) and mean
      gestational period among HCV positive cases and controls (p= 0.47). CONCLUSION:
      Prevalence of hepatitis C in pregnant women was 3.27%. Past history of surgical
      procedures was the most important factor for transmission of hepatitis C virus
      infection. No adverse effect on pregnancy outcome was observed in terms of
      gestational age, Apgar score and baby weight when compared with the controls.

PMID- 16300711
TI  - Outcome of surgery for bile duct injuries following laparoscopic cholecystectomy:
      Lahore General Hospital experience.
AB  - The objective of this study was to describe the management and outcome of repair
      in patients who sustained bile duct injuries (BDI) following laparoscopic
      cholecystectomy (LC). This study was conducted in the department of surgery,
      Postgraduate Medical Institute/Lahore General Hospital, Lahore, over a period of
      5 years from April 1999 to March 2004. Twelve patients of BDI following LC were
      managed during this period. Three out of 725 patients (0.4%) sustained BDI during
      LC in our own hospital, while 9 (75%) patients were referred from elsewhere.
      Strasberg type E accounted for majority of the injuries (66.6%). In 8 patients,
      Roux-en-Y hepaticojejunostomy was done. Excellent outcome after surgical
      reconstruction of BDI was noticed in 11(91%) patients.

PMID- 16300712
TI  - Left ventricular systolic dysfunction after transcatheter closure of a large
      patent ductus arteriosus.
AB  - A 12-year-old boy reported in outpatient department with history of shortness of
      breath and dyspnoea on moderate exertion. Physical examination was significant
      for bounding pulses and for a continuous murmur III/VI, best heard at the left
      upper sternal border. Echocardiography confirmed a large patent arterial duct
      with shortening fraction of 33%. He underwent successful transcatheter closure of
      the patent arterial, using Amplatzer duct occluder 12/10. Few hours later
      echocardiography revealed an unexpected, yet important depression of left
      ventricular systolic function with shortening fraction decreasing to 24% and then
      two weeks later decreasing further to 20%. At a follow-up after four months, he
      had improved clinically but left ventricular dysfunction still persisted with
      shortening fraction of 24%.

PMID- 16300713
TI  - Spontaneous cholecystocutaneous fistula.
AB  - We report a case of cholecystocutaneous fistula in a 90 years old female as a
      complication of gallstone disease. Patient presented with necrotizing fasciitis
      of anterior abdominal wall and cholecystocutaneous fistula. She was bedridden for
      the last 3 years due to cerebral vascular accident. She was a known case of
      chronic cholecystitis and 2 years back common bile duct stenting was done, in
      Jeddah, for obstructive jaundice but cholecystectomy was not done because patient
      was not fit for surgery.

PMID- 16300714
TI  - A huge malignant triton tumour.
AB  - A 45 years old man presented with progressively increasing abdominal mass of two
      years duration. The mass had rapidly increased in size in the past five months.
      The patient was emaciated, with a grossly protuberant abdomen. The biopsy
      revealed fibrosarcoma. Extirpation of the tumour was contemplated. A huge 82 x 53
      x 32 cm retroperitoneal mass was removed and the histopathology confirmed it as
      malignant triton tumour.

PMID- 16300715
TI  - Gastric stromal tumour.
AB  - This is a report of an old lady diagnosed with gastrointestinal stromal tumour
      (GIST) of the stomach with malignant potential and managed with subtotal
      gastrectomy. The patient showed good recovery. Four years postsurgery follow-up
      without any chemo-radiotherapy did not show any evidence of recurrent disease.
      Complete curative resection without any extensive lymphadenectomy has proven to
      provide four years disease-free survival.

PMID- 16300716
TI  - Hellp syndrome and subcapsular liver haematoma.
AB  - HELLP syndrome is a disease of variable presentation with high mortality and
      morbidity. Haemolysis in HELLP syndrome is microangiopathic. Obstruction of
      hepatic blood flow by fibrin deposits in sinusoids results in elevated liver
      enzymes. It also leads to periportal necrosis and, in severe cases, intrahepatic
      haemorrhage, subcapsular haematoma formation or hepatic rupture. This case report
      describes a patient presenting with mild hypertension with abruptio-placentae.
      She developed HELLP syndrome, subcapsular liver haematoma and pleural effusion
      after delivery.

PMID- 16300717
TI  - Sirenomelia (Mermaid baby).
AB  - Sirenomelia is a rare anomaly that rarely occurs as an isolated lesion. Several
      theories have been proposed regarding the etiopathogenesis. In this
      communication, we report a case of sirenomelia. Our patient was referred to
      hospital at the age of four hours. On examination, fusion of both lower limbs
      with hook shaped appendage, attached distally, absent genitalia and absent anal
      orifice was found. Spine was deficient in sacral region. Upper torso looked
      normal. Baby also had frothing from mouth. Abdomen was non-distended. Feeding
      tube no.10 was tried to pass through mouth, which got obstructed at the level of
      upper esophagus that suggested oesophageal atresia. The skeletogram revealed
      absence of pelvic bones, sacral agenesis, absent fibulae and fracture of both
      femora. The patient died at the age of 12 hours.

PMID- 16300718
TI  - Cancer treatment: what's ahead?
AB  - Surgery, chemotherapy, and radiation therapy are standard modalities for cancer
      treatment. Biological therapy (immunotherapy, biotherapy, or biological response
      modifier therapy) is a comparatively novel addition to this armamentarium.
      Biological therapies use the body's immune system, either directly or indirectly,
      to fight cancer or to lessen the side effects that may be caused by some cancer
      treatments. Biological therapeutic agents include interferons, interleukins,
      colony-stimulating factors, monoclonal antibodies, vaccines, gene therapy, and
      nonspecific immunomodulating agents. A promising form of cancer treatment is
      immunotherapy. Immunotherapy for cancer is essentially the stimulation of the
      immune system through a variety of reagents such as vaccines, infusion of T
      cells, or cytokines. These reagents act through one of several mechanisms
      including stimulating the anti-tumor response, decreasing suppressor mechanisms,
      altering tumor cells to increase their immunogenicity and making them more
      susceptible to immunologic defenses, and improving tolerance to cytotoxic agents
      or radiotherapy. This review describes some novel approaches in the immunotherapy
      in cancer.

PMID- 16300719
TI  - Burr hole craniostomy for chronic subdural hematoma.

PMID- 16300720
TI  - Earthquake in Northern Pakistan and AJK.

PMID- 16300721
TI  - Rabies control in Pakistan--the wise strategy.

PMID- 16300722
TI  - Intramolecular masking of nuclear localization signals: analysis of importin
      binding using a novel AlphaScreen-based method.
AB  - Active nuclear import of proteins requires the recognition of a nuclear
      localization sequence (NLS) by members of the importin (IMP) family of proteins.
      We have developed a modified AlphaScreen-based assay able to estimate the
      solution binding affinities of such interactions using biotinylated IMPs and His6
      tagged NLS-containing proteins. We describe this assay in detail as well as its
      application in documenting the phenomenon of intramolecular masking of NLSs using
      recombinant green fluorescent protein (GFP) fusion proteins containing sequences
      from the SV40 large tumor T antigen (T-ag). We also use it to examine, for the
      first time, IMP binding to the cancer cell-specific proapoptotic factor viral
      protein 3 (VP3) from the chicken anemia virus (CAV). High-affinity binding of the
      IMPalpha/beta heterodimer to the T-ag NLS was observed when the GFP tag was fused
      to its N terminus but not to its C terminus. Effects of flanking residues were
      also observed in GFP-T-ag fusion derivatives containing the Thr128 NLS
      inactivating mutation, whereby the absence of flanking sequences N terminal to
      the T-ag NLS appeared to decrease the specificity of the mutation in terms of
      oblating IMPalpha/beta binding. IMPbeta, but not IMPalpha or the IMPalpha/beta
      heterodimer, was found to bind to CAV VP3 with high affinity. Interestingly, GFP
      VP3(74-121) bound to IMPbeta with threefold higher affinity than the full-length
      protein, GFP-VP3(1-121), implying that the NLS is masked to a significant extent
      in the context of full-length protein. This may represent a regulatory mechanism
      to control nuclear import in a tumor cell-specific fashion.

PMID- 16300723
TI  - Effects of suppression and acceptance on emotional responses of individuals with
      anxiety and mood disorders.
AB  - The present investigation compared the subjective and physiological effects of
      emotional suppression and acceptance in a sample of individuals with anxiety and
      mood disorders. Sixty participants diagnosed with anxiety and mood disorders were
      randomly assigned to one of two groups. One group listened to a rationale for
      suppressing emotions, and the other group listened to a rationale for accepting
      emotions. Participants then watched an emotion-provoking film and applied the
      instructions. Subjective distress, heart rate, skin conductance level, and
      respiratory sinus arrhythmia were measured before, during, and after the film.
      Although both groups reported similar levels of subjective distress during the
      film, the acceptance group displayed less negative affect during the post-film
      recovery period. Furthermore, the suppression group showed increased heart rate
      and the acceptance group decreased heart rate in response to the film. There were
      no differences between the two groups in skin conductance or respiratory sinus
      arrhythmia. These findings are discussed in the context of the existing body of
      research on emotion regulation and current treatment approaches for anxiety and
      mood disorders.

PMID- 16300724
TI  - Acceptance and commitment therapy: model, processes and outcomes.
AB  - The present article presents and reviews the model of psychopathology and
      treatment underlying Acceptance and Commitment Therapy (ACT). ACT is unusual in
      that it is linked to a comprehensive active basic research program on the nature
      of human language and cognition (Relational Frame Theory), echoing back to an
      earlier era of behavior therapy in which clinical treatments were consciously
      based on basic behavioral principles. The evidence from correlational, component,
      process of change, and outcome comparisons relevant to the model are broadly
      supportive, but the literature is not mature and many questions have not yet been
      examined. What evidence is available suggests that ACT works through different
      processes than active treatment comparisons, including traditional Cognitive
      Behavior Therapy (CBT). There are not enough well-controlled studies to conclude
      that ACT is generally more effective than other active treatments across the
      range of problems examined, but so far the data are promising.

PMID- 16300725
TI  - Avoidance behavior in panic disorder: the moderating influence of perceived
      control.
AB  - The relations among anxiety sensitivity, perceived control, and agoraphobia were
      examined in 239 patients diagnosed with panic disorder (PD). Most patients
      exhibited agoraphobia accompanying their PD (98% situational avoidance; 90%
      experiential avoidance; and 80% endorsed interoceptive fear and avoidance).
      Anxiety sensitivity and perceived emotional control were associated with
      agoraphobia, and perceived threat control was found to moderate the relationship
      between anxiety sensitivity and agoraphobia. Lower levels of perceived control
      were associated with a stronger relationship between anxiety sensitivity and
      agoraphobia. Results were consistent for self-reported and clinician-rated
      agoraphobia. Implications for the role of perceived control in agoraphobia
      development and treatment are discussed.

PMID- 16300727
TI  - Effects of perfluorinated amphiphiles on backward swimming in Paramecium
      caudatum.
AB  - PFOS and PFOA are ubiquitous contaminants in the environment. We investigated the
      effects of fluorochemicals on calcium currents in Paramecium caudatum using its
      behavioral changes. Negatively charged amphiphiles prolonged backward swimming
      (BWS) of Paramecium. PFOS significantly prolonged BWS, while PFOA was less potent
      (EC(50): 29.8+/-4.1 and 424.1+/-124.0microM, respectively). The BWS prolongation
      was blocked by cadmium, indicating that the cellular calcium conductance had been
      modified. The positively charged amphiphile FOSAPrTMA shortened BWS (EC(50):
      19.1+/-17.3). Nonionic amphiphiles did not affect BWS. The longer-chain
      perfluorinated carboxylates PFNA and PFDA were more potent than PFOA (EC(50):
      98.7+/-20.1 and 60.4+/-10.1microM, respectively). However, 1,8
      perfluorooctanedioic acid and 1,10-perfluorodecanedioic acid did not prolong BWS.
      The critical micelle concentration (CMC) and BWS prolongation for negatively
      charged amphiphiles showed a clear correlation (r(2)=0.8008, p<0.001). In
      summary, several perfluorochemicals and PFOS and PFOA had similar effects in
      Paramecium, while chain length, CMC, and electric charge were major determinants
      of BWS duration.

PMID- 16300726
TI  - Phthalocyanine-mediated photodynamic therapy induces cell death and a G0/G1 cell
      cycle arrest in cervical cancer cells.
AB  - We have developed a series of novel photosensitizers which have potential for
      anticancer photodynamic therapy (PDT). Photosensitizers include zinc
      phthalocyanine tetra-sulphonic acid and a family of derivatives with amino acid
      substituents of varying alkyl chain length and degree of branching. Subcellular
      localization of these photosensitizers at the phototoxic IC(50) concentration in
      human cervical carcinoma cells (SiHa Cells) was similar to that of the lysosomal
      dye Lucifer Yellow. Subsequent nuclear relocalization was observed following
      irradiation with 665nm laser light. The PDT response was characterized using the
      Sulforhodamine B cytotoxicity assay. Flow cytometry was used for both DNA cell
      cycle and dual Annexin V-FITC/propidium iodide analysis. Phototoxicity of the
      derivatives was of the same order of magnitude as for tetrasulphonated
      phthalocyanine but with an overall trend of increased phototoxicity with
      increasing amino acid chain length. Our results demonstrate cell death,
      inhibition of cell growth, and G(0)/G(1) cell cycle arrest during the
      phthalocyanine PDT-mediated response.

PMID- 16300728
TI  - Induction of COX-2 protein expression by vanadate in A549 human lung carcinoma
      cell line through EGF receptor and p38 MAPK-mediated pathway.
AB  - Vanadate is a transition metal widely distributed in the environment. It has been
      reported that vanadate associated with air pollution particles can modify DNA
      synthesis, causing cell growth arrest, and apoptosis. Moreover, vanadium exposure
      was also found to cause the synthesis of inflammatory cytokines, such as
      interleukin-1, tumor necrosis factor-alpha, and prostaglandin E(2). Here, we
      found that exposure of A549 human lung carcinoma cells to vanadate led to
      extracellular signal-regulated kinase, c-Jun NH(2)-terminal protein kinases
      (JNKs), p38 mitogen-activated protein kinase (p38) activation, and COX-2 protein
      expression in a dose-dependent manner. SB203580, a p38 MAPK inhibitor, but not
      PD098059 and SP600125, specific inhibitor of MKK1 and selective inhibitor of JNK,
      respectively, suppressed COX-2 expression. Furthermore, the epithelial growth
      factor (EGF) receptor specific inhibitor (PD153035) reduced vanadate-induced COX
      2 expression. However, scavenging of vanadate-induced reactive oxygen species by
      catalase, a specific H(2)O(2) inhibitor, or DPI, an NADPH oxidase inhibitor,
      resulted in no inhibition on COX-2 expression. Together, we suggested that EGF
      receptor and p38 MAPK signaling pathway may be involved in vanadate-induced COX-2
      protein expression in A549 human lung carcinoma cell line.

PMID- 16300729
TI  - Metal mediated inhibition of methionine aminopeptidase by quinolinyl
      sulfonamides.
AB  - Quinolinyl sulfonamides, such as N-(quinolin-8-yl)methanesulfonamide (10) and N
      (5-chloroquinolin-8-yl)methanesulfonamide (11), were identified as potent
      methionine aminopeptidase (MetAP) inhibitors by high throughput screening of a
      diverse chemical library of small organic compounds. They showed different
      inhibitory potencies on Co(II)-, Ni(II)-, Fe(II)-, Mn(II)-, and Zn(II)-forms of
      Escherichia coli MetAP, and their inhibition is dependent on metal concentration.
      X-ray structures of E. coli MetAP complexed with 10 revealed that the inhibitor
      forms a metal complex with the residue H79 at the enzyme active site; the complex
      is further stabilized by an extended H-bond and metal interaction network.
      Analysis of the inhibition of MetAP by these inhibitors indicates that this is a
      typical mechanism of inhibition for many non-peptidic MetAP inhibitors and
      emphasizes the importance of defining in vitro conditions for identifying and
      evaluating MetAP inhibitors that will be capable of giving information relevant
      to the in vivo situation.

PMID- 16300730
TI  - RNA polymerase II mediated transcription from the polymerase III promoters in
      short hairpin RNA expression vector.
AB  - RNA polymerase III promoters of human ribonuclease P RNA component H1, human U6,
      and mouse U6 small nuclear RNA genes are commonly used in short hairpin RNA
      (shRNA) expression vectors due their precise initiation and termination sites.
      During transient transfection of shRNA vectors, we observed that H1 or U6
      promoters also express longer transcripts enough to express several reporter
      genes including firefly luciferase, green fluorescent protein EGFP, and red
      fluorescent protein JRed. Expression of such longer transcripts was augmented by
      upstream RNA polymerase II enhancers and completely inhibited by downstream polyA
      signal sequences. Moreover, the transcription of firefly luciferase from human H1
      promoter was sensitive to RNA polymerase II inhibitor alpha-amanitin. Our
      findings suggest that commonly used polymerase III promoters in shRNA vectors are
      also prone to RNA polymerase II mediated transcription, which may have negative
      impacts on their targeted use.

PMID- 16300731
TI  - ATF5 increases cisplatin-induced apoptosis through up-regulation of cyclin D3
      transcription in HeLa cells.
AB  - ATF5 transcription factor plays an essential role in hematopoietic and glioma
      cell survival and neuronal cell differentiation. Here, we report for the first
      time the pro-apoptosis role of ATF5 and identify Cyclin D3 as an ATF5-targeted
      apoptosis-related gene. The ectopic expression of ATF5 in HeLa cells could
      markedly increase cisplatin-induced apoptosis and the cleavage of Caspase-3, and
      induce Cyclin D3 mRNA expression via cooperation with E2F1 transcription factor.
      Moreover, the interference of Cyclin D3 expression by transfection with Cyclin D3
      RNAi could protect cells from ATF5-mediated apoptosis induced by cisplatin,
      indicating the contribution of Cyclin D3 in ATF5-mediated apoptosis. Taken
      together, these results suggest that ATF5 increases cisplatin-induced apoptosis
      through up-regulation of Cyclin D3 transcription, which elicits survival signals
      in HeLa cells.

PMID- 16300732
TI  - Organelle degradation during the lens and erythroid differentiation is
      independent of autophagy.
AB  - Autophagy is a bulk degradation system within cells through which cytoplasmic
      components are degraded within lysosomes. Primary roles of autophagy are
      starvation adaptation and intracellular protein quality control. In contrast to
      the ubiquitin-proteasome system, autophagy can also degrade organelles. Here we
      examined a possible role of autophagy in organelle degradation during lens and
      erythroid differentiation. We observed that autophagy occurs in embryonic lens
      cells. However, organelle degradation in lens and erythroid cells occurred
      normally in autophagy-deficient Atg5(-/-) mice. Our data suggest that degradation
      system(s) other than autophagy play major roles in organelle degradation during
      these processes.

PMID- 16300733
TI  - Recognition of cisplatin-damaged DNA by p53 protein: critical role of the p53 C
      terminal domain.
AB  - It was shown previously that the p53 protein can recognize DNA modified with
      antitumor agent cisplatin (cisPt-DNA). Here, we studied p53 binding to the cisPt
      DNA using p53 deletion mutants and via modulation of the p53-DNA binding by
      changes of the protein redox state. Isolated p53 C-terminal domain (CTD) bound to
      the cisPt-DNA with a significantly higher affinity than to the unmodified DNA. On
      the other hand, p53 constructs involving the core domain but lacking the C
      terminal DNA binding site (CTDBS) exhibited only small binding preference for the
      cisPt-DNA. Oxidation of cysteine residues within the CD of posttranslationally
      unmodified full length p53 did not affect its ability to recognize cisPt-DNA.
      Blocking of the p53 CTDBS by a monoclonal antibody Bp53-10.1 resulted in
      abolishment of the isolated CTD binding to the cisPt-DNA. Our results demonstrate
      a crucial role of the basic region of the p53 CTD (aa 363-382) in the cisPt-DNA
      recognition.

PMID- 16300734
TI  - Substrate phosphorylation affects degradation and interaction to endopeptidase
      24.15, neurolysin, and angiotensin-converting enzyme.
AB  - Recent findings from our laboratory suggest that intracellular peptides
      containing putative post-translational modification sites (i.e., phosphorylation)
      could regulate specific protein interactions. Here, we extend our previous
      observations showing that peptide phosphorylation changes the kinetic parameters
      of structurally related endopeptidase EP24.15 (EC 3.4.24.15), neurolysin (EC
      3.4.24.16), and angiotensin-converting enzyme (EC 3.4.15.1). Phosphorylation of
      peptides that are degraded by these enzymes leads to reduced degradation, whereas
      phosphorylation of peptides that interacted as competitive inhibitors of these
      enzymes alters only the K(i)'s. These data suggest that substrate phosphorylation
      could be one of the mechanisms whereby some intracellular peptides would escape
      degradation and could be regulating protein interactions within cells.

PMID- 16300735
TI  - Transcriptional activity of Pax3 is co-activated by TAZ.
AB  - Pax3 is a transcription factor which functions in embryonic development and human
      diseases. In a yeast two-hybrid screen with full-length Pax3 as bait, we isolated
      a clone encoding transcriptional co-activator with PDZ-binding motif (TAZ) from
      an E10.5 mouse embryo cDNA library. Co-immunoprecipitation and nuclear co
      localization of TAZ with Pax3 suggest that their association is functionally
      relevant. In situ hybridization revealed TAZ and Pax3 expression to partially
      overlap in the paraxial mesoderm, limb buds, and the neural tube. In C2C12
      myoblast cells and NIH3T3 cells, TAZ enhanced the transcriptional activity of
      Pax3 on artificial and microphthalmia-associated transcription factor promoter
      luciferase constructs, suggesting that TAZ can function as a co-activator of
      Pax3. Functional interaction between Pax3 and TAZ may provide a clue to
      clarifying the mechanism by which Pax3 serves as a transcriptional activator
      during embryogenesis.

PMID- 16300736
TI  - Analysis of a novel human gene, LOC92912, over-expressed in hypopharyngeal
      tumours.
AB  - We have identified by differential display a number of novel genes that are
      expressed in hypopharyngeal head and neck squamous cell carcinoma. We report here
      the characterisation of one of these novel human genes, LOC92912, that encodes a
      protein of 375 amino acids. The protein contains a RWD domain, a coiled-coil, and
      an E2 ubiquitin conjugating enzyme domain. LOC92912 is upregulated in about 85%
      of tumour samples. It is expressed in tumour masses and in invasive epithelium,
      and is located in the cytoplasm of cells. To gain insights into its functions, we
      identified potential interacting partners by immunoaffinity purification of the
      flag tagged protein followed by MALDI peptide mass fingerprinting mass
      spectrometry. Actin and six actin-binding proteins were unambiguously identified
      as potential interacting partners, suggesting that LOC92912's functions may be
      linked with the cytoskeleton. This novel human gene may represent a new target
      for cancer therapeutics.

PMID- 16300737
TI  - 5Alpha-bile alcohols function as farnesoid X receptor antagonists.
AB  - The farnesoid X receptor (FXR) is a bile acid/alcohol-activated nuclear receptor
      that regulates lipid homeostasis. Unlike other steroid receptors, FXR binds bile
      acids in an orientation that allows the steroid nucleus A ring to face helix 12
      in the receptor, a crucial domain for coactivator-recruitment. Because most
      naturally occurring bile acids and alcohols contain a cis-oriented A ring, which
      is distinct from that of other steroids and cholesterol metabolites, we
      investigated the role of this 5beta-configuration in FXR activation. The results
      showed that the 5beta-(A/B cis) bile alcohols 5beta-cyprinol and bufol are potent
      FXR agonists, whereas their 5alpha-(A/B trans) counterparts antagonize FXR
      transactivation and target gene expression. Both isomers bound to FXR, but their
      ability to induce coactivator-recruitment and thereby induce transactivation
      differed. These findings suggest a critical role for the A-ring orientation of
      bile salts in agonist/antagonist function.

PMID- 16300738
TI  - Ubiquitin-dependent degradation of adenovirus E1A protein is inhibited by BS69.
AB  - Adenovirus E1A protein perturbs the cell cycle and promotes cell transformation.
      Although E1A is relatively unstable, regulation of E1A stability has not been
      fully elucidated. Here, we showed that E1A was ubiquitinated and degraded using a
      proteasome in vivo system. Interestingly, we found that BS69, one of the E1A
      binding proteins, inhibited ubiquitination of E1A. BS69 mutants lacking the MYND
      domain could not bind to E1A and did not inhibit ubiquitination of E1A. Moreover,
      we demonstrated that overexpression of BS69 stabilized E1A in vivo. These results
      suggest that BS69 controls E1A stability via inhibition of ubiquitination.

PMID- 16300739
TI  - Exploring the antioxidant property of bioflavonoid quercetin in preventing DNA
      glycation: a calorimetric and spectroscopic study.
AB  - Reducing sugars for example glucose, fructose, etc., and their phosphate
      derivatives non-enzymatically glycate biological macromolecules (e.g., proteins,
      DNA and lipids) and is related to the production of free radicals. Here we
      present a novel study, using differential scanning calorimetry (DSC) along with
      UV/Vis absorption and photon correlation spectroscopy (PCS), on normal and
      glycated human placenta DNA and have explored the antioxidant property of the
      naturally occurring polyhydroxy flavone quercetin (3,3',4',5,7
      pentahydroxyflavone) in preventing the glycation. The decrease in the absorption
      intensity of DNA in presence of sugars clearly indicates the existence of sugar
      molecules between the two bases of a base pair in the duplex DNA molecule.
      Variations were perceptible in the PCS relaxation profiles of normal and glycated
      DNA. The melting temperature of placenta DNA was decreased when glycated
      suggesting a decrease in the structural stability of the double-stranded glycated
      DNA. Our DSC and PCS data showed, for the first time, that the dramatic changes
      in the structural properties of glycated DNA can be prevented to a significant
      extent by adding quercetin. This study provides valuable insights regarding the
      structure, function, and dynamics of normal and glycated DNA molecules,
      underlying the manifestation of free radical mediated diseases, and their
      prevention using therapeutically active naturally occurring flavonoid quercetin.

PMID- 16300740
TI  - Interaction of the stress protein p8 with Jab1 is required for Jab1-dependent p27
      nuclear-to-cytoplasm translocation.
AB  - p8 is an 80 amino-acid polypeptide identified because of its remarkable over
      expression in the stressed pancreas. This protein, apparently devoid of enzymatic
      activity, is a powerful regulator of several intracellular pathways, suggesting
      that it has to interact with several molecular partners to modulate their
      activity. We used two-hybrid screening of a pre-transformed human testes cDNA
      library to identify some of these partners. One of them was the multifunctional
      protein Jab1, its interaction with p8 being confirmed by His6-pull down and co
      immunoprecipitation assays. In addition, we could show that the two proteins co
      localized in the cell. Our functional data demonstrate that Jab1 requires direct
      interaction with p8 to induce the translocation of p27 from nucleus to cytoplasm
      and its subsequent degradation. Experiments showing that the knock-down of p8
      expression results in a strong inhibition of Jab1 activity confirmed that the
      mechanism by which Jab1 promotes cell growth by decreasing p27 level is p8
      dependent.

PMID- 16300741
TI  - Neurokinin-1 receptor in peripheral nerve terminals mediates thermal
      hyperalgesia.
AB  - Neurokinin-1 receptor (NK-1) plays an important role in nociception. The present
      study was to explore whether activation of peripheral NK-1 receptor, especially
      expressed on primary sensory afferents, could induce hyperalgesia and sensitize C
      type sensory afferents. (1) Intraplantar administration of NK-1 agonist [Sar9,
      Met(O2)11]SP (Sar-SP, 0.2, 1 nmol, 20 microl) produced significant thermal
      hyperalgesia and edema, which was blocked by co-injection of NK-1 antagonist
      WIN51,708 (10 nmol). But in the rats with compound 48/80 treatment for mast cell
      depletion, the Sar-SP-induced edema, but not hyperalgesia, was attenuated. (2)
      Close-arterial injection of Sar-SP (1 nmol, 0.1 ml) excited and sensitized
      sensory C afferents of the sural nerve to heat stimuli. The results suggest
      involvement of NK-1 receptors expressed on the peripheral afferent terminals in
      thermal hyperalgesia mediated by directly sensitizing C-type sensory afferents.

PMID- 16300742
TI  - The crystal structure of an odorant binding protein from Anopheles gambiae:
      evidence for a common ligand release mechanism.
AB  - The Anopheles gambiae mosquito is the main vector of malaria transmission in sub
      Saharan Africa. We present here a 1.5A crystal structure of AgamOBP1, an odorant
      binding protein (OBP) from the A. gambiae mosquito. The protein crystallized as a
      dimer with a unique binding pocket consisting of a continuous tunnel running
      through both subunits of the dimer and occupied by a PEG molecule. We demonstrate
      that AgamOBP1 undergoes a pH dependent conformational change that is associated
      with reduced ligand binding. A predominance of acid-labile hydrogen bonds
      involving the C-terminal loop suggests a mechanism in which a drop in pH causes C
      terminal loop to open, leaving the binding tunnel solvent exposed, thereby
      lowering binding affinity for ligand. Because proteins from two distantly related
      insects also undergo a pH dependent conformational change involving the C
      terminus that is associated with reduced ligand affinity, our results suggest a
      common mechanism for OBP activity.

PMID- 16300743
TI  - Inhibition of glycerophosphate-dependent H2O2 generation in brown fat
      mitochondria by idebenone.
AB  - The established protective effect of coenzyme Q (CoQ) analogs is dependent on the
      location of reactive oxygen species (ROS) generation. One of these analogs-
      idebenone (hydroxydecyl-ubiquinone) is used as an antioxidative therapeutic drug.
      We tested its scavenging effect on the glycerophosphate (GP)-dependent ROS
      production as this enzyme was shown as a new site in the mitochondrial
      respiratory chain where ROS can be generated. We observed that idebenone inhibits
      both GP- and succinate-dependent ROS production. Idebenone and CoQ1 were found to
      be more efficient in the scavenging activity (IC50: 0.052 and 0.075 microM,
      respectively) than CoQ3 (IC50: 45.8 microM). Idebenone also inhibited
      ferricyanide (FeCN)-activated, GP-dependent ROS production. Our data thus extend
      previous findings on the scavenging effect of idebenone and show that it can also
      eliminate GP-dependent ROS generation.

PMID- 16300744
TI  - Molecular cloning and characterization of rat LC3A and LC3B--two novel markers of
      autophagosome.
AB  - Rat microtubule-associated protein light chain 3 (LC3) is a homologue of yeast
      Atg8, an essential component of autophagy. Following synthesis, the C-terminus of
      rat LC3 is cleaved by a cysteine protease-Atg4, to produce LC3-I, which is
      located in cytosolic fraction. LC3-I can be converted to LC3-II through the
      processing by Atg7 (E1-like enzyme) and Atg3 (E2-like enzyme). LC3-II is modified
      by phosphatidylethanolamine on C-terminus and binds tightly to autophagosomal
      membrane. Here we reported the cloning of two novel variants of rat LC3, named
      LC3A and LC3B, respectively, and LC3B is an alternative splicing variant of LC3.
      LC3A, LC3B, and LC3 showed different expression patterns in rat tissues,
      suggesting a functional divergence among these proteins. When LC3A and LC3B were
      overexpressed, both exhibited two forms (18 and 16 kDa, representing types of I
      and II, separately), which might be due to post-translational modification
      including the characteristic C-terminal cleavage at these two proteins as similar
      to that found in rat LC3 and yeast Atg8. Subcellular localization demonstrated
      that both LC3A and LC3B are colocalized with LC3 and associated with the
      autophagic membranes. Mutation analysis further revealed that the conserved
      Gly120 residues of LC3A and LC3B are essential for their characteristic C
      terminal cleavage and localization to autophagic membranes. Present data
      suggested that LC3A and LC3B could also be used as two novel autophagosomal
      markers.

PMID- 16300745
TI  - Generation of adenosine A3 receptor functionally humanized mice for the
      evaluation of the human antagonists.
AB  - Although the adenosine A(3) receptor (A3AR), which is a G(i/o) protein-coupled
      receptor, has attracted considerable interest as a potential target for drugs
      against asthma or inflammation, the in vivo evaluation of the antagonists using
      rodents in the first step of drug development has been hampered by the lack of
      highly potent antagonists for the rodent A3AR. To evaluate the pharmacological
      effects of human A3AR antagonists in mice, we previously generated A3AR-humanized
      mice, in which the mouse A3AR gene was replaced by its human counterpart.
      However, the human A3AR did not lead to the phosphoinositide 3-kinase (PI3K)
      gamma-signaling pathway such as IgE/antigen-dependent mast cell degranulation,
      probably due to the uncoupling of the mouse G(i/o) protein(s). To overcome the
      uncoupling, we here generated A3AR functionally humanized mice by replacing the
      mouse A3AR gene with a human/mouse chimeric A3AR sequence in which whole
      intracellular regions of the human A3AR were substituted for the corresponding
      regions of the mouse A3AR. The chimeric A3AR led to intracellular Ca(2+)
      elevation and activation of the PI3Kgamma-signaling pathway, which are equivalent
      to the actions induced by A3AR in wild-type mice. The human A3AR antagonist had
      the same binding affinities for the chimeric A3AR as the human A3AR and
      completely antagonized this potentiation. This is the first direct evidence that
      the uncoupling of mouse G protein(s) to the human A3AR is due to a sequence
      difference in the intracellular regions of A3AR. The A3AR functionally humanized
      mice can be widely employed for pharmacological evaluations of the human A3AR
      antagonists.

PMID- 16300746
TI  - A protective role for proteinase activated receptor 2 in airways of
      lipopolysaccharide-treated rats.
AB  - Proteinase activated receptor-2 (PAR2), a seven transmembrane domain G protein
      coupled receptor, is expressed on airway epithelium and smooth muscle cells and
      over-expressed in human airways under pathological conditions, such as asthma and
      chronic obstructive pulmonary disease (COPD). However, the role of PAR2 in
      airways has not yet been defined. Aim of the present study, was to evaluate the
      in vitro rat bronchial response to a synthetic peptide activating PAR2 (PAR2-AP;
      SLIGRL), following an in vivo treatment with bacterial lipopolysaccharide (LPS).
      Bronchi from LPS-treated animals showed an increased relaxant response to PAR2
      AP, compared to naive animals, the effect was maximum after 20-h pre-treatment
      and reduced by epithelium removal. Western blot analysis showed an increased PAR2
      protein expression on bronchi removed 20h after LPS treatment. PAR2-AP-induced
      bronchorelaxation was inhibited by ibuprofen, by the selective cyclooxygenase2
      (COX-2) inhibitor, diisopropyl fluorophosphate (DFP) and partially by the
      calcitonin gene related peptide (CGRP) antagonist, rat-CGRP([8-37]). Furthermore,
      there was a strong immunoreactivity for COX-2 on bronchial epithelium of LPS
      treated rats. Prostaglandin E2 (PGE2) tissue release and CGRP tissue content were
      significantly increased following tissue incubation with PAR2-AP. The in vivo LPS
      treatment in rats strongly increases the bronchorelaxant effect of PAR2-AP, this
      effect correlates with an increased tissue protein receptor expression and the
      COX-2 localization on bronchial epithelium. Our work supports a role for PAR2 as
      a defence mechanism aimed to preserve bronchial functionality under systemic
      inflammatory conditions; both COX-2-derived PGE2 and CGRP are involved in this
      effect.

PMID- 16300747
TI  - The genetics of depression: a review.
AB  - Major depressive disorder (MDD) is common and moderately heritable. Recurrence
      and early age at onset characterize cases with the greatest familial risk. Major
      depressive disorder and the neuroticism personality trait have overlapping
      genetic susceptibilities. Most genetic studies of MDD have considered a small set
      of functional polymorphisms relevant to monoaminergic neurotransmission. Meta
      analyses suggest small positive associations between the polymorphism in the
      serotonin transporter promoter region (5-HTTLPR) and bipolar disorder, suicidal
      behavior, and depression-related personality traits but not yet to MDD itself.
      This polymorphism might also influence traits related to stress vulnerability.
      Newer hypotheses of depression neurobiology suggest closer study of genes related
      to neurotoxic and neuroprotective (neurotrophic) processes and to overactivation
      of the hypothalamic-pituitary axis, with mixed evidence regarding association of
      MDD with polymorphisms in one such gene (brain-derived neurotrophic factor
      [BDNF]). Several genome-wide linkage studies of MDD and related traits have been
      reported or are near completion. There is some evidence for convergence of
      linkage findings across studies, but more data are needed to permit meta
      analysis. Future directions will include more intensive, systematic study of
      linkage candidate regions and of the whole genome for genetic association; gene
      expression array studies; and larger-scale studies of gene-environment
      interactions and of depression-related endophenotypes.

PMID- 16300748
TI  - Amplitudes of head movements during putative eye-only saccades.
AB  - The mechanisms allowing humans and other primates to dissociate head and eye
      movements during saccades are poorly understood. A more precise knowledge of head
      movement behavior during apparent eye-only saccades may provide insight into
      those mechanisms. We studied the distributions of head amplitude in normal
      humans. In half of the subjects, these distributions indicated the presence of a
      population of minor ("residual") head movements during eye-only saccades,
      distinct from the continuum of head movements generated during frank eye-head
      saccades. Like full-sized head movements, the residual movements grew in
      proportion to target eccentricity, indicating their drive is derived from the
      premotor command for the saccade. Furthermore, their amplitudes related most
      strongly to the head amplitudes obtained when subjects produced full-sized head
      movements and were reduced when subjects were instructed to perform exclusively
      eye-only saccades. Both observations suggest that the drive for residual head
      movements originates downstream of the point in which the head movement command
      diverges from the generalized gaze shift command. The results are consistent with
      a model of head control in which a neural gate prevents the common gaze shift
      command from reaching the head premotor circuitry whenever an eye-only saccade is
      desired. However, the gate is either imperfect or the multiple pathways that
      relay gaze shift signals to the head motor circuitry allow for the gate to be
      circumvented. The results underscore the need for physiological studies to probe
      neuronal activity related to neck activation during eye-only saccades.

PMID- 16300749
TI  - Analysis of inducible costimulatory molecule participation during the induction
      and elicitation of granulomatous responses to mycobacterial and schistosomal
      antigens.
AB  - The contribution of inducible costimulatory molecule (ICOS) to Th1 and Th2 cell
      mediated immune responses was examined in well-defined pathogen antigen-elicited
      models of cell-mediated granuloma formation. Th1 and Th2 granulomas were
      respectively induced by intravenous challenge of CBA/J mice with Mycobacteria
      bovis purified protein derivative (PPD) or Schistosoma mansoni egg (SEA) antigen
      coated beads. Effects of anti-ICOS blocking antibody on granulomas and lymphoid
      responses were assessed during elicitation and sensitization. Anti-ICOS treatment
      during the elicitation abrogated Th1- but not Th2-cell-mediated granuloma
      formation. Treatment during sensitization augmented SEA-bead granulomas and Th2
      cytokines in lymphoid tissue. Anti-ICOS reduced the primary inflammatory response
      to PPD- but not to SEA-beads, despite comparable induction of ICOS-ligand and
      ICOS+ T cells. Treatment did not prevent early development of IFNgamma producing
      cells. Thus, post-activation effector Th1 activity was subject to ICOS blockade
      and chronic treatment caused diversion to Th2 dominance likely by eroding Th1
      effector function or survival.

PMID- 16300750
TI  - Comparative study of respiratory burst induced by phorbol ester and zymosan in
      human granulocytes.
AB  - OBJECTIVES: We have comparatively evaluated respiratory burst and some steps of
      its signaling in human granulocytes towards different stimuli. MATERIALS AND
      METHODS: An alternative method to remove erythrocytes by dextran differential
      sedimentation was employed. Respiratory burst (RB) was assessed in a flow
      cytometer by the oxidation of a fluorescent probe (dichlorodihydrofluorescein).
      Stimuli were phorbol ester (PMA) and zymosan. RESULTS: Granulocytes obtained with
      dextran sedimentation mounted a normal RB for the two stimuli but cells obtained
      by erythrocyte lysis were ineffective to respond to zymosan (P < 0.05). EGTA did
      not affect PMA-induced, but inhibited zymosan-induced RB (P < 0.05). PMA-induced
      RB was blocked by a protein kinase C inhibitor (P < 0.05), whereas zymosan was
      not. Microfilament integrity was essential for zymosan but not for PMA, whereas
      microtubule depolymerization does not seem to be essential for both stimuli.
      Granulocytes obtained from recently diagnosed leukemia patients responded
      relatively well to both stimuli but after chemotherapy, the response to zymosan
      was increased whereas cells were unable to respond to PMA. CONCLUSION: The use of
      the proposed method allows the study of both RB and phagocytosis, making it
      useful to study these granulocyte responses in the clinical and experimental
      settings.

PMID- 16300751
TI  - Investigation of oxidative stress and some antioxidants in patients with acute
      and chronic viral hepatitis B and the effect of interferon-alpha treatment.
AB  - OBJECTIVE: The aim of the study was to determine oxidative stress in patients
      with acute and chronic viral hepatitis B. DESIGN AND METHODS: 23 (11 F, 12 M)
      healthy controls, 23 (8 F, 15 M) patients with acute viral hepatitis B (AVHB) and
      25 (9 F, 16 M) patients with chronic viral hepatitis B (CVHB) were studied. Serum
      malondialdehyde (MDA), conjugated dienes (CD), ALT, AST, total and direct
      bilirubins, beta-carotene and whole blood reduced glutathione (GSH) levels of all
      subjects were measured. In patients with CVHB, these parameters were measured
      both before and 6 months after treatment with interferon-alpha (IFN-alpha).
      RESULTS: MDA, CD, ALT, AST and total and direct bilirubin levels of the patients
      with AVHB and CVHB before treatment were significantly higher (P<0.001) whereas
      GSH and beta-carotene levels were lower (P<0.001) than those of the controls.
      MDA, CD, GSH, beta-carotene, ALT, AST and total and direct bilirubin levels of
      the patients with CVHB returned approximately to normal levels 6 months after
      treatment with IFN-alpha. CONCLUSION: Our results clearly show that patients with
      AVHB and CVHB are under the influence of increased oxidative stress (MDA and CD
      were increased) associated with lower levels of some antioxidants (beta-carotene
      and GSH). These impairments return to normal levels after IFN-alpha treatment of
      CVHB patients. These findings suggest that antioxidant supplementation might be
      considered in patients with acute or chronic hepatitis B.

PMID- 16300752
TI  - chokh/rx3 specifies the retinal pigment epithelium fate independently of eye
      morphogenesis.
AB  - Despite the importance of the retinal pigment epithelium (RPE) for vision, the
      molecular processes involved in its specification are poorly understood. We
      identified two new mutant alleles for the zebrafish gene chokh (chk), which
      display a reduction or absence of the RPE. Unexpectedly, the neural retina (NR)
      in chk is specified and laminated, indicating that the regulatory network leading
      to NR development is largely independent of the RPE. Genetic mapping and
      molecular characterization revealed that chk encodes Rx3. Expression analyses
      show that otx2 and mitfb are not expressed in the prospective RPE of chk,
      indicating that the retinal homeobox gene rx3 acts upstream of the molecular
      network controlling RPE specification. Cellular transplantations demonstrate that
      rx3 function is autonomously required to specify the prospective RPE. Though rx2
      is also absent in chk, neither rx2 nor rx1 is required for RPE development. Thus,
      our data provide the first indication that, in addition to controlling optic lobe
      evagination and proliferation, chk/rx3 also determines cellular fate.

PMID- 16300753
TI  - Novel heterochronic functions of the Caenorhabditis elegans period-related
      protein LIN-42.
AB  - LIN-42, the Caenorhabditis elegans homolog of the Period (Per) family of
      circadian rhythm proteins, functions as a member of the heterochronic pathway,
      regulating temporal cell identities. We demonstrate that lin-42 acts broadly,
      timing developmental events in the gonad, vulva, and sex myoblasts, in addition
      to its well-established role in timing terminal differentiation of the
      hypodermis. In the vulva, sex myoblasts, and hypodermis, lin-42 activity prevents
      stage-specific cell division patterns from occurring too early. This general
      function of timing stage-appropriate cell division patterns is shared by the
      majority of heterochronic genes; their mutation temporally alters stage-specific
      division patterns. In contrast, lin-42 function in timing gonad morphogenesis is
      unique among the known heterochronic genes: inactivation of lin-42 causes the
      elongating gonad arms to reflex too early, a phenotype which implicates lin-42 in
      temporal regulation of cell migration. Three additional isoforms of lin-42 are
      identified that expand our view of the lin-42 locus and significantly extend the
      homology between LIN-42 and other PER family members. We show that, similar to
      PER proteins, LIN-42 has a dynamic expression pattern; its levels oscillate
      relative to the molts during postembryonic development. Transformation rescue
      studies indicate lin-42 is bipartite with respect to function. Intriguingly, the
      hallmark PAS domain is dispensable for LIN-42 function in transgenic animals.

PMID- 16300754
TI  - An 8-bp deletion in mNOTCH4 intron 10 leads to its retention in mRNA and to
      synthesis of a truncated protein.
AB  - Notch signaling participates in the development of multicellular organisms by
      maintaining self-renewal potential or inducing differentiation of numerous
      tissues. In this study, we characterized Notch4, the evolutionary most distant
      and least studied Notch family member. We identified a Notch4 inter-strain
      polymorphism with a previously undescribed mRNA variant. This longer Notch4 mRNA,
      which represented up to one-third of total Notch4 mRNA, resulted from intron 10
      retention. Analysis of Notch4 intron 10 revealed that an 8-bp deletion, reducing
      its length from 68 to 60 bp, strictly correlated with its retention. Further
      experiments demonstrated that intron length was the only cause of the mis
      splicing. Moreover, this mRNA variant resulted in a truncated protein containing
      half the extracellular domain of Notch4, including the ligand-binding domain.

PMID- 16300755
TI  - S14 protein in breast cancer cells: direct evidence of regulation by SREBP-1c,
      superinduction with progestin, and effects on cell growth.
AB  - Most breast cancers exhibit brisk lipogenesis, and require it for growth. S14 is
      a lipogenesis-related nuclear protein that is overexpressed in most breast
      cancers. Sterol response element-binding protein-1c (SREBP-1c) is required for
      induction of lipogenesis-related genes, including S14 and fatty acid synthase
      (FAS), in hepatocytes, and correlation of SREBP-1c and FAS expression suggested
      that SREBP-1c drives lipogenesis in tumors as well. We directly tested the
      hypothesis that SREBP-1c drives S14 expression and mediates lipogenic effects of
      progestin in T47D breast cancer cells. Dominant-negative SREBP-1c inhibited
      induction of S14 and FAS mRNAs by progestin, while active SREBP-1c induced
      without hormone and superinduced in its presence. Changes in S14 mRNA were
      reflected in protein levels. A lag time and lack of progestin response elements
      indicated that S14 and FAS gene activation by progestin is indirect. Knockdown of
      S14 reduced, whereas overexpression stimulated, T47D cell growth, while
      nonlipogenic MCF10a mammary epithelial cells were not growth-inhibited. These
      data directly demonstrate that SREBP-1c drives S14 gene expression in breast
      cancer cells, and progestin magnifies that effect via an indirect mechanism. This
      supports the prediction, based on S14 gene amplification and overexpression in
      breast tumors, that S14 augments breast cancer cell growth and survival.

PMID- 16300756
TI  - Changes in vesicular glutamate transporter 2, vesicular GABA transporter and
      vesicular acetylcholine transporter labeling of sacrocaudal motoneurons in the
      spastic rat.
AB  - Spasticity of the midline musculature can significantly hinder performing
      transfers and lead to development of pressure sores. Currently, significant gaps
      exist in our knowledge of the pathophysiology involved in spasticity development
      following SCI, especially regarding the axial musculature. The goals of this
      study were: (1) to determine the effects of S(2) transection on the number and
      distribution of glutamatergic, GABAergic and cholinergic inputs on more caudal
      motoneurons, (2) to correlate these changes with the development of spasticity
      within the tail musculature, which are the caudal counterparts to the axial
      musculature. Animals with S(2) spinal transection were tested behaviorally for
      the progression of spasticity within the tail musculature. At 1, 2, 4, or 12
      weeks post-injury, the animals were sacrificed and temporal changes in
      glutamatergic, GABAergic, and cholinergic inputs to sacrocaudal motoneurons were
      assessed using antibodies for the specific vesicular transporter of each
      neurotransmitter and confocal microscopy. At 1 week post-injury, when the tail
      musculature demonstrated decreased responsiveness, an overall increase in the
      ratio of excitatory to inhibitory input to sacrocaudal motoneurons was observed.
      From 2 to 12 weeks post-injury, when the tail musculature demonstrated increased
      reflex behavior, an overall decrease in the ratio of excitatory to inhibitory
      inputs was observed. Additionally, from 2 to 12 weeks following spinal
      transection, a progressive loss of cholinergic labeling of sacrocaudal
      motoneurons was observed. The increase in the overall level of excitation with a
      concomitant loss of cholinergic influence following spinal transection could, in
      part, explain the development of spasticity within the tail musculature.

PMID- 16300757
TI  - 3alpha-OL-5-beta-pregnan-20-one hemisuccinate, a steroidal low-affinity NMDA
      receptor antagonist improves clinical rating scores in a rabbit multiple infarct
      ischemia model: synergism with tissue plasminogen activator.
AB  - We previously showed that the neuroactive steroid 3alpha-ol-5-beta-pregnan-20-one
      hemisuccinate (ABHS), a low-affinity NMDA receptor antagonist, improves behavior
      in rabbits following spinal cord ischemia. The present study assessed whether
      this also occurs following cerebral ischemia. We used the rabbit small clot
      embolic stroke model (RSCEM), a model of multiple infarct ischemia, which has a
      well-defined behavioral endpoint. Quantal analysis for each treatment determines
      microclots (mg) that produce neurologic dysfunction in 50% of a group of animals
      (P(50)), with treatment considered beneficial if it increases the P(50) compared
      to controls. ABHS (25 mg/kg) injected 5 min post-embolization significantly (P =
      0.046) increased the P(50) to 2.60 +/- 0.69 mg compared to 1.15 +/- 0.19 mg in
      controls but was ineffective at longer intervals. For combination studies with
      tissue plasminogen activator (tPA), a cumulative control curve (P(50) = 1.18 +/-
      0.25 mg) was used for statistical comparisons. Low-dose tPA (0.9 mg/kg) and ABHS,
      given 60 min post-embolization, improved behavior synergistically (P(50) = 2.44
      +/- 0.44 mg), compared to tPA (P(50) = 1.25 +/- 0.25 mg) or ABHS (P(50) = 1.05 +/
      0.24 mg) alone. A standard tPA dose (3.3 mg/kg) significantly increased the
      P(50) at 60 (2.69 +/- 0.19 mg) but not 180 min (1.28 +/- 0.31 mg) post
      embolization. However, when combined with ABHS, an effect was evident even 180
      min post-embolization (P(50) = 2.31 +/- 0.48 mg). Although the therapeutic window
      for ABHS is limited, it significantly enhanced neuroprotection by low-dose tPA
      and increased the therapeutic window for tPA, suggesting that it may be most
      useful as a co-therapy with thrombolytics for stroke.

PMID- 16300758
TI  - Caspase inhibition therapy abolishes brain trauma-induced increases in Abeta
      peptide: implications for clinical outcome.
AB  - The detrimental effects of traumatic brain injury (TBI) on brain tissue integrity
      involve progressive axonal damage, necrotic cell loss, and both acute and delayed
      apoptotic neuronal death due to activation of caspases. Post-injury accumulation
      of amyloid precursor protein (APP) and its toxic metabolite amyloid-beta peptide
      (Abeta) has been implicated in apoptosis as well as in increasing the risk for
      developing Alzheimer's disease (AD) after TBI. Activated caspases proteolyze APP
      and are associated with increased Abeta production after neuronal injury.
      Conversely, Abeta and related APP/Abeta fragments stimulate caspase activation,
      creating a potential vicious cycle of secondary injury after TBI. Blockade of
      caspase activation after brain injury suppresses apoptosis and improves
      neurological outcome, but it is not known whether such intervention also prevents
      increases in Abeta levels in vivo. The present study examined the effect of
      caspase inhibition on post-injury levels of soluble Abeta, APP, activated caspase
      3, and caspase-cleaved APP in the hippocampus of nontransgenic mice expressing
      human Abeta, subjected to controlled cortical injury (CCI). CCI produced brain
      tissue damage with cell loss and elevated levels of activated caspase-3, Abeta(1
      42) and Abeta(1-40), APP, and caspase-cleaved APP fragments in hippocampal
      neurons and axons. Post-CCI intervention with intracerebroventricular injection
      of 100 nM Boc-Asp(OMe)-CH(2)F (BAF, a pan-caspase inhibitor) significantly
      reduced caspase-3 activation and improved histological outcome, suppressed
      increases in Abeta and caspase-cleaved APP, but showed no significant effect on
      overall APP levels in the hippocampus after CCI. These data demonstrate that
      after TBI, caspase inhibition can suppress elevations in Abeta. The extent to
      which Abeta suppression contributes to improved outcome following inhibition of
      caspases after TBI is unclear, but such intervention may be a valuable
      therapeutic strategy for preventing the long-term evolution of Abeta-mediated
      pathology in TBI patients who are at risk for developing AD later in life.

PMID- 16300759
TI  - Developmentally regulated changes in femoral nerve regeneration in the mouse and
      rat.
AB  - The attractive influence of muscle on regenerating motor neuron axons is well
      known. Less is known, however, about the intrinsic abilities of different nerve
      pathways to support these axons prior to end-organ contact. The age at which a
      nerve injury is sustained is also known to affect the relationship between
      regenerating motor axons and muscle. The femoral nerve model, with its distinct
      muscle and cutaneous pathways, is ideal to study intrinsic pathway properties
      because the influence of end-organs can easily be removed surgically. However,
      recent results using this model in adult mice are at odds with the same model in
      neonatal rats. To reconcile these discrepancies, we used the femoral nerve model
      to examine possible age differences in intrinsic pathway support for regenerating
      motor neurons in the mouse and rat. Rat motor neurons showed a preference to
      regenerate into the muscle pathway after axotomy at 3 weeks of age, but this
      preference was lost after axotomy at 6 weeks of age. Interestingly, mouse motor
      neurons showed no pathway preference after axotomy at 3 weeks of age but
      developed one for the cutaneous pathway after axotomy at 6 weeks of age. These
      results suggest that in the absence of end-organ contact there is no general
      preference for motor neurons to project to the muscle pathway.

PMID- 16300760
TI  - Glial metabolites of tryptophan and excitotoxicity: coming unglued.

PMID- 16300762
TI  - Simultaneous functional magnetic resonance imaging in the rat spinal cord and
      brain.
AB  - Functional magnetic resonance imaging (fMRI) method was developed to investigate
      the pattern and temporal relationship in neuronal pathways of brain and spinal
      cord. Signal intensity changes correlating with stimulation patterns were
      observed simultaneously in the rat spinal cord and brain using fMRI at 9.4 T.
      Electrical stimulation of the forepaw was used to elicit activity. A quadrature
      volume RF coil covering both brain and the cervical spinal cord was used. Sets of
      fast spin echo (FSE) images were acquire simultaneously for both brain and spinal
      cord fMRI. Experiments were repeated in single animal and across animals.
      Activities within the dorsal horn of the spinal cord and within the somatosensory
      cortex were observed consistently within each animal as well as across animals.

PMID- 16300761
TI  - Nerve growth factor regulates substance P in adult sensory neurons through both
      TrkA and p75 receptors.
AB  - Expression of the nociceptive peptide, substance P (SP) is regulated by the
      neurotrophin, nerve growth factor (NGF), and exogenous exposure to high levels of
      NGF increases its cellular content and release. NGF utilizes two receptors, the
      NGF-specific tyrosine kinase receptor, TrkA, and also the non-specific
      neurotrophin receptor, p75(NTR) (p75). The purpose of this study is to determine
      the relative involvement of these receptors in nociception. To investigate the
      role of TrkA in SP signaling, sensory neurons from adult rats were grown in vitro
      and exposed to a TrkA-blocking antibody. Pretreatment with the antibody inhibited
      NGF-induced SP elevation. Furthermore, when neurons were exposed to K252a, a
      relatively specific TrkA kinase inhibitor, the NGF effect on SP was also
      inhibited. K252a did not prevent SP up-regulation in cells exposed to forskolin
      or glial cell line-derived neurotrophic factor (GDNF), two agents which increase
      SP expression independently of TrkA. When p75 was blocked by antiserum, SP up
      regulation by NGF was also inhibited. The antiserum neither impacted neuronal
      survival or basal levels of SP expression, nor did it inhibit SP up-regulation
      induced by forskolin. Two other neurotrophins, which are also ligands for p75,
      brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) did not block
      NGF-induced SP up-regulation, raising the possibility that activated p75 is able
      to cooperate in SP regulation regardless of which neurotrophin ligand occupies
      it. Our data suggest that NGF up-regulation of SP expression requires the
      involvement of both TrkA and p75, although the specific contribution of each
      receptor to SP signaling remains to be determined.

PMID- 16300763
TI  - Plasmodium falciparum: polymorphism in the MSP-1 gene in Indian isolates and
      predominance of certain alleles in cerebral malaria.
AB  - Polymorphism in the block-2 region of merozoite surface protein-1 gene in 69
      North Indian Plasmodium falciparum isolates was studied by PCR and RFLP using Dra
      1 endonuclease. On the basis of molecular weight of the PCR products,
      considerable size polymorphism in target gene was seen and 69 isolates were
      classified into five allelic types. On RFLP, the isolates in three allelic types
      were further divided into two sub-allelic types each and thus eight genetic types
      could be identified. Interestingly, all five allelic types were identified in 47
      isolates from uncomplicated (non-cerebral) malaria patients while only two
      allelic types (Type 2 and 3) were seen amongst 22 isolates from cerebral malaria
      patients. Furthermore, on RFLP, one subtype (2A) was predominantly seen in
      cerebral malaria patients and one subtype (3A) was exclusively found in cerebral
      malaria patients. These observations suggest that a few, comparatively more
      virulent isolates prevalent in an area may cause severe disease (cerebral
      malaria) which can be identified by molecular techniques like PCR-RFLP.

PMID- 16300764
TI  - The effects of adrenalectomy and corticosterone replacement on maternal memory in
      postpartum rats.
AB  - Hormones associated with parturition prime rats to behave maternally, although
      hormonal changes are not necessary for these behaviors to occur. Experience with
      pups after birth enhances maternal responsiveness after a period of isolation,
      creating a maternal memory. The purpose of this study was to determine the role
      of corticosterone in the formation of maternal memory. Adrenalectomy or sham
      surgeries were performed in late gestation with corticosterone or vehicle pellets
      being given to adrenalectomized rats. Pups were removed immediately following
      parturition, and half of the rats received 4 h of pup experience, while the other
      half received only brief pup experience associated with parturition. Ten days
      following pup experience, foster pups were given to all rats. Latency to become
      maternal and maternal behaviors on the first 2 days of re-exposure and the first
      two maternal days were recorded. Among adrenalectomized rats given
      corticosterone, 4-h experience with pups decreased maternal latency when compared
      to brief experience with pups. This maternal experience effect was not found in
      comparisons between adrenalectomized rats not given corticosterone. In addition,
      corticosterone decreased latencies regardless of pup experience. Corticosterone
      also increased maternal behavior upon initial exposure to foster pups. In
      conclusion, corticosterone enhanced maternal memory and initial maternal behavior
      in postpartum rats.

PMID- 16300765
TI  - Reliability of mitochondrial DNA in an acanthocephalan: the problem of
      pseudogenes.
AB  - The utility of mitochondrial DNA as a molecular marker for evolutionary studies
      is well recognized. However, several problems can arise when using mitochondrial
      DNA, one of which is the presence of nuclear mitochondrial pseudogenes, or Numts.
      Pseudogenes of cytochrome oxidase I were preferentially amplified from
      Acanthocephalus lucii (Acanthocephala) using a universal PCR approach. To verify
      the presence and abundance of pseudogenes, length heterogeneity analysis of the
      PCR fragments was performed. PCR products obtained with universal primers often
      contained fragments of different sizes. Cloned sequences from universal PCR
      products nearly always contained sequence abnormalities such as indels and/or
      stop codons. Based on these sequences, new primers were developed to specifically
      target mitochondrial DNA. Sequences obtained with these specific primers lacked
      abnormalities. Phylogenetic analysis produced a single most parsimonious tree in
      which pseudogenes obtained with universal primers grouped together as did
      putative mitochondrial DNA sequences obtained with specific primers. The pattern
      of codon bias observed in the pseudogenes suggests a single nuclear integration
      event from the mitochondria. This is the first reported occurrence of pseudogenes
      in an acanthocephalan, and it demonstrates the potential dangers associated with
      the use of universal primers.

PMID- 16300766
TI  - The effect of desiccation and low temperature on the viability of eggs and
      emerging larvae of the tick, Rhipicephalus (Boophilus) microplus (Canestrini)
      (Ixodidae).
AB  - Process-based population models need sound and comprehensive data on an animal's
      response to climatic factors if they are to function reliably under a wide range
      of climatic conditions. To this end, different aged egg masses of the livestock
      tick, Rhipicephalus (Boophilus) microplus, were either desiccated in atmospheres
      with saturation deficits of 5, 10, 15 or 20 mmHg at 20 or 26 degrees C, or
      chilled at temperatures of 5, 10 or 14 degrees C with a saturation deficit of 1
      mmHg for varying periods. The survival rate of the eggs through to hatching was
      related to the initial age of the eggs, the severity of the treatments and the
      duration of exposure. We established a relationship between desiccation and
      weight loss of eggs and, secondarily between weight loss and mortality. Mortality
      increased with weight loss until it reached 100% when the weight loss was about
      35%. Low temperatures were increasingly detrimental to eggs as they reduced from
      14 to 5 degrees C. Freshly laid eggs were more susceptible to both low
      temperatures and desiccation than were older eggs. Larvae emerging from eggs that
      were stressed by either cold or desiccation lived for a shorter time under
      optimal conditions than did larvae from eggs incubated under optimal conditions.
      Larvae from eggs with the same hatching rate had the same viability, whether the
      stress was induced by desiccation or low temperatures. Models were developed to
      describe the dynamics of weight loss of eggs with desiccation, the accumulation
      of cold stress of the eggs, and their effects on egg survival and larval
      viability. These data provide a sound basis for the development of predictive
      models for use under field conditions, although the response of different aged
      eggs to low temperatures was too variable to allow us to develop an accurate
      model to describe that relationship. Field models will also need to take diurnal
      temperature fluctuations into account.

PMID- 16300767
TI  - Eimeria maxima: the influence of host genotype on parasite reproduction as
      revealed by quantitative real-time PCR.
AB  - The influence of host genotype on susceptibility to infection with Eimeria
      species has long been recognised, but beyond monitoring pathological severity or
      magnitude of oocyst excretion attempts to quantify fluctuations in parasite
      reproduction within the host have previously relied upon labour-intensive
      microscopic analysis. The development and application of a quantitative real-time
      PCR assay has opened this biological 'black box', permitting the sensitive and
      reproducible enumeration of parasite genomes throughout the course of infection.
      Generic and species-specific quantitative PCR methods are described, based upon
      the conserved 5S ribosomal RNA coding sequence of nine avian and murine Eimeria
      species and the Eimeria maxima MIC1 gene, respectively. These complementary
      assays have been applied to study the influence of host genotype on resistance to
      infection with E. maxima, revealing significant differences in parasite load
      between 'resistant' Line C and 'susceptible' Line 15I inbred chickens 5 days
      after infection. Parasite DNA remained detectable up to 20 days post-infection;
      11 days after the last oocysts had been detected leaving the host.

PMID- 16300768
TI  - Inhibition of atherogenesis in LDLR knockout mice by systemic delivery of adeno
      associated virus type 2-hIL-10.
AB  - Atherosclerosis is an inflammatory disease of the arteries. Interleukin-10 (IL
      10) is known to be an anti-inflammatory cytokine which might be useful for
      counteracting the development of atherosclerosis. As long-term systemic cytokine
      delivery is prohibitively expensive, gene therapy might be a suitable approach.
      To test this idea, low-density lipoprotein receptor (LDLR) knockout mice were
      injected with recombinant adeno-associated virus type 2 (AAV)/interleukin-10
      virus or AAV/granulocyte macrophage-colony stimulating factor (GM-CSF) virus and
      then put on a high-cholesterol diet. Upon harvesting the animals at 18 weeks,
      elevated blood lipids could be documented and AAV/IL-10 and AAV/GM-CSF DNA and
      mRNA could be found in various mouse organs. The mice receiving the AAV/IL-10
      virus had significantly lower levels of atherogenesis (Sudan IV-staining and
      histology) than the untreated or the AAV/GM-CSF-treated animals, dropping from
      53% to 17% (p < 0.05). The aortas of the AAV/IL-10-treated animals displayed
      higher IL-10 expression and lower CD68 and nitrotyrosine expression. These data
      are similar to those of Yoshioka et al. [Yoshioka, T, Okada, T, Maeda, Y, et al.
      Adeno-associatedvirus vector-mediated interleukin-10 gene transfer inhibits
      atherosclerosis in apolipoprotein E-deficient mice. Gene Ther 2004;11:1772-9] in
      which AAV/IL-10 was delivered into the tibial muscle of ApoE-deficient mice,
      instead of tail vein injection used here. These data indicate that systemic
      AAV/IL-10 gene delivery, with resulting inhibition of inflammation and oxidative
      stress, was able to limit atherogenesis, and suggest that this approach is worthy
      of further study.

PMID- 16300769
TI  - Pyridoxine prevents dysfunction of endothelial cell nitric oxide production in
      response to low-density lipoprotein.
AB  - Low-density lipoprotein (LDL) inhibits endothelium-dependent vasorelaxation. The
      aim of this study was to determine whether pyridoxine supplementation improves
      indices of LDL-induced endothelial dysfunction. Human umbilical vein endothelial
      cells (HUVEC) were incubated with native LDL (nLDL) from healthy subjects,
      oxidized LDL (oxLDL, formed by nLDL oxidation) or nLDL from type II diabetic
      patients (dLDL), in the absence or presence of pyridoxine; nitric oxide synthase
      (NOS) activity, cyclic GMP and expression of NOS isoforms were measured, as well
      as thiobarbituric acid reactive substances (TBARS) in HUVEC supernatants and
      amino acid concentrations in HUVEC lysates. All LDL species inhibited total NOS
      activity, whilst increasing the much smaller Ca2+-independent component of NOS
      activity, the effects of oxLDL being greatest and those of nLDL smallest; in
      accordance with these findings, NOS type 3 expression decreased and NOS type 2
      expression increased, with a resultant decrease in bioactive nitric oxide (NO),
      in HUVEC treated with each LDL species, with the same rank order of potency. LDL
      species also increased TBARS in HUVEC supernatants as well as homocysteine
      concentrations in HUVEC lysates, nLDL < dLDL < oxLDL. Pyridoxine largely
      prevented all LDL-induced changes in NOS activity and isoform expression, as well
      as in TBARS and homocysteine. The findings suggest that pyridoxine prevents LDL
      induced dysfunction of endothelial cell NO generation, most likely through its
      antioxidant effects as well as through its effects on cellular homocysteine
      metabolism. This has important potential therapeutic implications for
      cardiovascular disease prevention.

PMID- 16300770
TI  - One-month administration of hydroxytyrosol, a phenolic antioxidant present in
      olive oil, to hyperlipemic rabbits improves blood lipid profile, antioxidant
      status and reduces atherosclerosis development.
AB  - The present study analysed the effects of hydroxytyrosol (HT) on blood lipids,
      antioxidant status and the progression of aortic lesions in hyperlipemic rabbits.
      Sixty-four rabbits were distributed into eight groups of animals (n = 8). Animal
      groups C, A and H were fed for 1-month with a control diet containing sunflower
      oil (C), an atherogenic diet (A) high in saturated fat and cholesterol or the A
      diet together with HT, respectively. The other five groups were fed for 2-months
      with diets C or A (groups CC or AA, respectively), or for 1-month with the A-diet
      followed by a further month with diet C, extra virgin olive oil diet (O) or diet
      C with HT (groups AC, AO and AH, respectively). Four milligram of HT/kg body
      weight were used in the study. Fifty and 42% decrease in total cholesterol and
      triacylglycerols, respectively, and a 2.3-fold increase in HDL-cholesterol were
      observed in the AH group but not in the H group. The HT-supplemented groups
      improved their antioxidant status and reduced the size of atherosclerotic lesions
      measured as intimal layer areas of the aortic arch when compared with control
      animals. We conclude that HT supplementation may have cardioprotective effects in
      vivo.

PMID- 16300771
TI  - Respiratory flow in obstructed airways.
AB  - Chronic obstructive pulmonary disease (COPD) is one of the most common diseases
      in human community. The COPD always results in inflammation that leads to
      narrowing and obstruction of the airways. The obstructive airways have
      significant effect on respiratory flow. In order to understand the flow
      phenomenon in such obstructive airways, four three-dimensional four-generation
      lung models based on the 23-generation model of Weibel [1963. Morphometry of the
      Human Lung. Springer, Academic Press, Berlin, New York] are generated. The fully
      three-dimensional incompressible laminar Navier-Stokes equations are solved using
      computational fluid dynamics (CFD) solver on unstructured tetrahedral meshes.
      Therein, a symmetric four-generation airway model is served as the reference, the
      other three models are considered to be obstructed at each generation,
      respectively. The calculation results show that the obstructive airway has
      significant influence on the air flow in both up- and down-stream airways and it
      even results in flow separation in the conjunction region. The re-circulation
      cell blocks the air from entering the downstream branches. This may be the reason
      why COPD patients should breathe gently, and this also provides some valuable
      information for medicine powder deposition.

PMID- 16300772
TI  - Nonlinear adsorption isotherm as a tool for understanding and characterizing
      molecularly imprinted polymers.
AB  - Molecularly imprinted polymers (MIPs) have frequently been characterized by
      quantities which are easily determined from experiments but have no theoretical
      foundation. This makes it difficult to compare different MIP preparations or to
      transfer MIP based methods to different experimental conditions. Since the
      adsorption isotherms of MIPs are markedly nonlinear, one can build a better
      characterization strategy on isotherms as shown by examples in this paper.

PMID- 16300773
TI  - Development and application of a sol-gel immunosorbent-based method for the
      determination of isoproturon in surface water.
AB  - An immunosorbent was fabricated by encapsulation of monoclonal anti-isoproturon
      antibodies in sol-gel matrix. The immunosorbent-based loading, rinsing and
      eluting processes were optimized. Based on these optimizations, the sol-gel
      immunosorbent (SG-IS) selectively extracted isoproturon from an artificial
      mixture of 68 pesticides. In addition to this high selectivity, the SG-IS proved
      to be reusable. The SG-IS was combined with liquid chromatography-tandem mass
      spectrometry (LC-MS-MS) to determine isoproturon in surface water, and the linear
      range was up to 2.2 microg/l with correlation coefficient higher than 0.99 and
      relative standard deviation (RSD) lower than 5% (n=8). The limit of quantitation
      (LOQ) for 25-ml surface water sample was 5 ng/l.

PMID- 16300774
TI  - Novel polymer monolith microextraction using a poly(methacrylic acid-ethylene
      glycol dimethacrylate) monolith and its application to simultaneous analysis of
      several angiotensin II receptor antagonists in human urine by capillary zone
      electrophoresis.
AB  - Novel polymer monolith microextraction (PMME) using a poly(methacrylic acid
      ethylene glycol dimethacrylate) (poly(MAA-EGDMA)) monolith in conjunction with
      capillary zone electrophoresis (CZE) was developed for the determination of
      several angiotensin II receptor antagonists (ARA-IIs) in human urine. The
      extraction device consisted of a regular plastic syringe (1 mL), a poly(MAA
      EGDMA) monolithic capillary (2 cm x 530 microm I.D.) and a plastic pinhead
      connecting the former two components seamlessly. The extraction was achieved by
      driving the sample solution through the monolithic capillary tube using a syringe
      infusion pump, and for the desorption step, an aliquot of organic solvent was
      injected via the monolithic capillary and collected into a vial for subsequent
      analysis by CZE. The best separation was realized at 25 kV using a buffer that
      consisted of 50% acetonitrile and 50% buffer solution (v/v) containing 10 mM
      disodium hydrogenphosphate (adjusted to pH 2.3 with 1M hydrochloric acid). The
      method was successfully applied to the determination of telmisartan (T),
      irbesartan (I) and losartan (L) in urine samples with candesartan (C) as internal
      standard, yielding the detection limit of 15-20 ng/mL. Close correlation
      coefficients (R>0.999) and excellent method reproducibility were obtained for all
      the analytes over a linear range of 0.08-3 microg/mL.

PMID- 16300775
TI  - Anticipating colloidal instabilities in cationic vesicle dispersions by measuring
      collective motions with dynamic light scattering.
AB  - Vesicle dispersions are useful for many applications from medicinal to consumer
      products. However, using these dispersions requires some knowledge of and control
      over their colloidal properties. Measuring interparticle interactions between
      vesicles should allow framing the problem in terms of Smoluchowski kinetic models
      and consequently anticipating time-dependent aggregation and coalescence for the
      dispersions. However, this can be a difficult task for many complex mixtures. A
      primary goal of this paper is to show that it is possible to measure
      interparticle potential between small vesicles by measuring the concentration
      dependent collective motion using dynamic light scattering. These measurements
      allow determination of the second virial coefficient for the dispersion,
      providing a convenient platform for summing all contributions to the interaction
      potential over all vesicle conformations, thus making the analysis of complex
      mixtures more tractable. As a verification of the approach, a comparison is made
      to dispersions in which the stability is governed solely by electrostatics, using
      existing techniques to anticipate instabilities. A second goal of this paper is
      to build a simple potential model in which the Smoluchowski model can be used to
      quantitatively anticipate the aggregation behavior of the small vesicle
      dispersion. Together, these observations constitute a convenient approach to
      anticipating the behavior of vesicle (and other) dispersions in complex mixtures.

PMID- 16300776
TI  - Raspberry-like composite polymer particles by self-assemble heterocoagulation
      based on a charge compensation process.
AB  - Nano-sized poly(ethylene glycol dimethacrylate-co-acylic acid) (poly(EGDMA-co
      AA)) were effectively self-assembled on poly(divinylbenzene-co-styryl
      methylpyridinium chloride) (poly(DVB-co-StMPyCl)) surfaces to form the raspberry
      like composite by a charge compensation mechanism through the affinity complex
      between carboxylic group and pyridinium group. The effects of pH and salt
      electrolyte on the morphology of the self-assembled polymer composites were
      investigated. The resulting heterocoagulates were highly stable in water and acid
      solution. These heterocoagulates were reversible through the self-assembly in
      acidic or neutral media and the dissociation in the basic medium due to the
      charge compensation through the strong affinity complex between hydroxide anion
      and pyridinium group cation. The resulting heterocoagulates were characterized
      with scanning electron microscopy (SEM), field emission scanning electron
      microscopy (FESEM) and Fourier transform infrared spectroscopy (FTIR). As a
      result, a new method for tuning the structure of a charge compensation directed
      polymer composite was developed.

PMID- 16300777
TI  - Quantitative characterization of food products by two-dimensional D-T2 and T1-T2
      distribution functions in a static gradient.
AB  - We present new NMR techniques to characterize food products that are based on the
      measurement of two-dimensional diffusion-T2 relaxation and T1-T2 relaxation
      distribution functions. These measurements can be performed in magnets of modest
      strength and low homogeneity and do not require pulsed gradients. As an
      illustration, we present measurements on a range of dairy products that include
      milks, yogurt, cream, and cheeses. The two-dimensional distribution functions
      generally exhibit two distinct components that correspond to the aqueous phase
      and the liquid fat content. The aqueous phase exhibits a relatively sharp peak,
      characterized by a large T1/T2 ratio of around 4. The diffusion coefficient and
      relaxation times are reduced from the values for bulk water by an amount that is
      sample specific. The fat signal has a similar signature in all samples. It is
      characterized by a wide T2 distribution and a diffusion coefficient of 10(-11)
      m2/s for a diffusion time of 40 ms, determined by bounded diffusion in the fat
      globules of 3 microm diameter.

PMID- 16300778
TI  - The removal of uranium(VI) from aqueous solutions onto activated carbon: kinetic
      and thermodynamic investigations.
AB  - The adsorption of uranium(VI) from aqueous solutions onto activated carbon has
      been studied using a batch adsorber. The parameters that affect the uranium(VI)
      adsorption, such as contact time, solution pH, initial uranium(VI) concentration,
      and temperature, have been investigated and optimized conditions determined
      (contact time 240 min; pH 3.0+/-0.1; initial uranium concentration 100 mg/L;
      temperature 293.15 K). The experimental data were analyzed using sorption kinetic
      models (pseudo-first- and pseudo-second-order equations) to determine the
      equation that fits best our experimental results. Equilibrium isotherm studies
      were used to evaluate the maximum sorption capacity of activated carbon and
      experimental results showed this to be 28.30 mg/g. The Freundlich, Langmuir, and
      Dubinin-Radushkevich (D-R) models have been applied and the data correlate well
      with Freundlich model and that the sorption is physical in nature (the activation
      energy Ea=7.91 kJ/mol). Thermodynamic parameters (DeltaHads0=-50.53 kJ/mol,
      DeltaSads0=-98.76 J/mol K, DeltaGads(293.15 K)0=-21.61 kJ/mol) showed the
      exothermic heat of adsorption and the feasibility of the process.

PMID- 16300779
TI  - Structure and property studies of hybrid xerogels containing bridged positively
      charged 1,4-diazoniabicycle[2.2.2]octane dichloride.
AB  - The compound di-3-n-propyltrimethoxysilane (1,4-diazoniabicycle[2.2.2]octane)
      dichloride, [(MeO)3Si(CH2)3N+ (CH2CH2)3N+ (CH2)3Si(OME)3]Cl2 was obtained and was
      used as a precursor reagent to obtain hybrid xerogels where the organic molecule
      was bonded to a silica framework by reacting the ends of both sides of the
      precursor reagent. That is, both -Si(OME)3 groups react with
      tetraethylorthosilicate (TEOS) by hydrolysis-condensation reactions. The
      resulting hybrid xerogels with variable C/Si mole ratios were prepared and
      analyzed and their textural characteristics determined. The samples prepared
      presented micropores with diameter 1.5 nm, the chain length of which matched with
      the estimated length of the organic bridging group. The charged organic bridging
      groups allow the immobilization of hexacyanoferrate ions by an ion exchange
      process. The electron transfer process of the hexacyanoferrate anionic complex
      confined in the pores of the matrices was studied by cyclovoltammetry.

PMID- 16300780
TI  - Measurement and calculation of surface tension of molten Sn-Bi alloy.
AB  - The surface tension of molten Sn-Bi (mole fraction X(Bi) = 0.455) alloy has been
      determined by the sessile drop method at oxygen partial pressure (P(O2)) of
      1.0x10(-6) MPa and different temperatures. The experimental results have been
      analyzed and discussed, and the positive temperature coefficient of surface
      tension of molten Sn-Bi alloy has been elucidated. The surface tension of this
      molten alloy has also been obtained by calculation using STCBE based on Butler's
      equation and thermodynamic data. The experimental results agree well with the
      calculation values.

PMID- 16300781
TI  - Probing the viscoelastic response of glassy polymer films using atomic force
      microscopy.
AB  - The mechanical properties of glassy films and glass surfaces have been studied
      using an atomic force microscope (AFM) through various imaging modes and
      measuring methods. In this paper, we discuss the viscoelastic response of a
      glassy surface probed using an AFM. We analyzed the force-distance curves
      measured on a glassy film or a glassy surface at temperatures near the glass
      transition temperature, Tg, using a Burgers model. We found that the material's
      characteristics of reversible anelastic response and viscous creep can be
      extracted from a force-distance curve. Anelastic response shifts the repulsive
      force-distance curve while viscous creep strongly affects the slope of the
      repulsive force-distance curve. When coupled with capillary force, due to the
      condensation of a thin layer of liquid film at the tip-surface joint, the
      anelasticity and viscous creep can alter the curve significantly in the
      attractive region.

PMID- 16300782
TI  - Thermodynamics of micellization of tetraethylammonium perfluorooctylsulfonate in
      water.
AB  - Conductivity, density, and sound velocity measurements as functions of
      temperature were made on tetraethylammonium perfluorooctylsulfonate solutions to
      determine the Krafft point, the dependence on temperature of the critical micelle
      concentration, the micellar ionization degree, and several thermodynamic
      properties: Gibbs free energy, enthalpy and entropy of micellization, apparent
      molar partial volume, thermal expansion coefficient, and the adiabatic
      compressibility factor of both micellized and unmicellized surfactants. Important
      changes occur at about 30 degrees C. Results are interpreted on the basis of
      dehydration of surfactant on micellization and on temperature increase.

PMID- 16300783
TI  - Understanding the role of surfactants on the preparation of ZnS nanocrystals.
AB  - We have synthesized surface modified ZnS nanoparticles of size 2-3 nm using non
      ionic surfactant-stabilized reverse emulsions. The non-ionic surfactants in the
      Span series, i.e. sorbitan monolaurate (Span 20) and sorbitan monooleate (Span
      80) of hydrophilic-lipophilic balance (HLB) values of 8.6 and 4.3, respectively,
      have been used for the stabilization of emulsions. The role of these surfactants
      in controlling the size and properties of the ZnS nanoparticles has been
      discussed. The triethylamine (TEA) has been proved to be the effective surface
      modifying (capping) agent for the preparation of free-standing ZnS nanoparticles.
      The Span 20 with the higher HLB value of 8.6 has been found to be highly suitable
      in synthesizing TEA-capped ZnS nanoparticles of smaller size and higher
      photophysical characteristics compared to that of the Span 80 of lower HLB value
      of 4.3. A mechanism for the formation of TEA-capped ZnS nanoparticles from the
      surfactant-stabilized reverse emulsions has been proposed.

PMID- 16300784
TI  - Recent and fossil nematode parasites (Nematoda: Mermithidae) of neotropical ants.
AB  - The following new recent species of mermithid (Nematoda) parasites of Neotropical
      ants are described: Meximermis ectatommi n.gen., n. sp. from workers of Ectatomma
      ruidum Roger in Southern Mexico, Agamomermis cephaloti n. sp. from a worker of
      Cephalotes minutus (Fab.) collected in Brazil, Agamomermis ecitoni n. sp. from a
      worker of Eciton burchellii Westwood collected in Venezuela and Agamomermis
      costaricensis n. sp. from a worker of Odontomachus hastatus (Fab.) collected in
      Costa Rica. In addition, a fossil mermithid parasite of a worker of Linepithema
      sp. from Dominican amber is described as Heydenius myrmecophila n. sp. These
      parasites represent the first descriptions of Neotropical ant mermithids and
      together with previous records listed here, show that ant infection by mermithids
      in the Neotropics is widespread and has occurred for at least 20-30 million
      years.

PMID- 16300785
TI  - Detection of Deformed wing virus, a honey bee viral pathogen, in bumble bees
      (Bombus terrestris and Bombus pascuorum) with wing deformities.
AB  - Honey bees (Apis mellifera) productively infected with Deformed wing virus (DWV)
      through Varroa destructor (V. destructor) during pupal stages develop into adults
      showing wing and other morphological deformities. Here, we report for the first
      time the occurrence of bumble bees (Bombus terrestris, Bombus pascuorum)
      exhibiting wing deformities resembling those seen in clinically DWV-infected
      honey bees. Using specific RT-PCR protocols for the detection of DWV followed by
      sequencing of the PCR products we could demonstrate that the bumble bees were
      indeed infected with DWV. Since such deformed bumble bees are not viable DWV
      infection may pose a serious threat to bumble bee populations.

PMID- 16300786
TI  - Molecular basis for nucleotide-binding specificity: role of the exocyclic amino
      group "N2" in recognition by a guanylyl-ribonuclease.
AB  - Proteins interact with nucleotides to perform a multitude of functions within
      cells. These interactions are highly specific; however, the molecular basis for
      this specificity is not well understood. To identify factors critical for protein
      guanine nucleotide recognition the binding of two closely related ligands,
      guanosine 3'-monophosphate (3'GMP) and inosine 3'-monophosphate (3'IMP), to
      Ribonuclease Sa (RNase Sa), a small, guanylyl-endoribonuclease from Streptomyces
      aureofaciens, was compared using isothermal titration calorimetry, NMR, X-ray
      crystallography and molecular dynamics simulations. This comparison has allowed
      for the determination of the contribution of the exocyclic amino group "N2" of
      the guanine base to nucleotide binding specificity. Calorimetric measurements
      indicate that RNase Sa has a higher affinity for 3'GMP (K=(1.5+/-0.2)x10(5)) over
      3'IMP (K=(3.1+/-0.2)x10(4)) emphasizing the importance of N2 as a key determinant
      of RNase Sa guanine binding specificity. This result was unexpected as the
      published structural data for RNase Sa in complex with 3'GMP showed only a
      potential long-range interaction (>3.3A) between N2 and the side-chain of Glu41
      of RNase Sa. The observed difference in affinity is largely due to a reduction in
      the favorable enthalpy change by 10 kJ/mol for 3'IMP binding as compared to 3'GMP
      that is accompanied by a significant difference in the heat capacity changes
      observed for binding the two ligands. To aid interpretation of the calorimetric
      data, the first crystal structure of a small, guanylyl ribonuclease bound to
      3'IMP was determined to 2.0 A resolution. This structure has revealed small yet
      unexpected changes in the ligand conformation and differences in the
      conformations of the side-chains contacting the sugar and phosphate moieties as
      compared to the 3'GMP complex. The structural data suggest the less favorable
      enthalpy change is due to an overall lengthening of the contacts between RNase Sa
      and 3'IMP as compared to 3'GMP. The long-range interaction between N2 and Glu41
      is critical for positioning of the nucleotide in the binding cleft for optimal
      contact formation. Thus, combined, the data demonstrate how a long-range
      interaction can have a significant impact on nucleotide binding affinity and
      energetics.

PMID- 16300787
TI  - Identification of native and non-native structure in kinetic folding
      intermediates of apomyoglobin.
AB  - Site-directed mutagenesis has been used to probe the interactions that stabilize
      the equilibrium and burst phase kinetic intermediates formed by apomyoglobin.
      Nine bulky hydrophobic residues in the A, E, G and H helices were replaced by
      alanine, and the effects on protein stability and kinetic folding pathways were
      determined. Hydrogen exchange pulse-labeling experiments, with NMR detection,
      were performed for all mutants. All of the alanine substitutions resulted in
      changes in proton occupancy or an increased rate of hydrogen-deuterium exchange
      for amides in the immediate vicinity of the mutation. In addition, most mutations
      affected residues in distant parts of the amino acid sequence, providing insights
      into the topology of the burst phase intermediate and the interactions that
      stabilize its structure. Differences between the pH 4 equilibrium molten globule
      and the kinetic intermediate are evident: the E helix region plays no discernible
      role in the equilibrium intermediate, but contributes significantly to
      stabilization of the ensemble of compact intermediates formed during kinetic
      refolding. Mutations that interfere with docking of the E helix onto the
      preformed A/B/G/H helix core substantially decrease the folding rate, indicating
      that docking and folding of the E helix region occurs prior to formation of the
      apomyoglobin folding transition state. The results of the mutagenesis experiments
      are consistent with rapid formation of an ensemble of compact burst phase
      intermediates with an overall native-like topological arrangement of the A, B, E,
      G, and H helices. However, the experiments also point to disorder in docking of
      the E helix and to non-native contacts in the kinetic intermediate. In
      particular, there is evidence for translocation of the H helix by approximately
      one helical turn towards its N terminus to maximize hydrophobic interactions with
      helix G. Thus, the burst phase intermediate observed during kinetic refolding of
      apomyoglobin consists of an ensemble of compact, kinetically trapped states in
      which the helix docking appears to be topologically correct, but in which there
      are local non-native interactions that must be resolved before the protein can
      fold to the native structure.

PMID- 16300788
TI  - Actin interacts with CCT via discrete binding sites: a binding transition-release
      model for CCT-mediated actin folding.
AB  - The chaperones prefoldin and the cytosolic chaperonin CCT-containing TCP-1 (CCT)
      guide the cytoskeletal protein actin to its native conformation. Performing an
      alanine scan of actin, we identified discrete recognition determinants for CCT
      interaction. Interestingly, one of these is similar and functional in the non
      homologous protein Cdc20, suggesting that some of the binding information in the
      CCT target proteins is shared. The information in actin for recognition by CCT
      and for folding is different, as all but one of the mutants in the recognition
      determinants are folding-competent. In addition, some other actin mutants remain
      CCT-arrested and are not released in a native conformation, whereas others do
      fold but remain bound to CAP. Kinetic experiments provide evidence that CCT
      mediated folding of non-native actin occurs in at least two steps, in which
      initially the recognition determinant 245-249 contacts CCT and the other
      determinants interact at later stages. Actin mutants that are CCT-arrested
      demonstrate that some regions neighbouring the recognition determinants are
      involved in modulating the correct folding transitions of actin on CCT, or its
      release from this chaperonin. Further, we found that the ATP binding of actin is
      not a prerequisite for its release, and we suggest that CAP may be involved in
      charging the nucleotide. Based on the kinetics of CCT binding and folding of
      actin and actin mutants, we propose a multi-step recognition-transition-release
      model. This also implies that the currently accepted notion of CCT-mediated actin
      folding is probably more complex.

PMID- 16300789
TI  - Three key residues underlie the differential affinity of the TGFbeta isoforms for
      the TGFbeta type II receptor.
AB  - TGFbeta1, beta2, and beta3 are 25kDa homodimeric polypeptides that play crucial
      non-overlapping roles in development, tumor suppression, and wound healing. They
      exhibit 70-82% sequence identity and transduce their signals by binding and
      bringing together the TGFbeta type I and type II receptors, TbetaRI and TbetaRII.
      TGFbeta2 differs from the other isoforms in that it binds TbetaRII weakly and is
      dependent upon the co-receptor betaglycan for function. To explore the
      physicochemical basis underlying these differences, we generated a series of
      single amino acid TbetaRII variants based on the crystal structure of the
      TbetaRII:TGFbeta3 complex and examined these in terms of their TGFbeta isoform
      binding affinity and their equilibrium stability. The results showed that
      TbetaRII Ile53 and Glu119, which contact TGFbeta3 Val92 and Arg25, respectively,
      together with TbetaRII Asp32, Glu55, and Glu75, which contact TGFbeta3 Arg94,
      each contribute significantly, between 1 kcal mol(-1) to 1.5 kcal mol(-1), to
      ligand binding affinities. These contacts likely underlie the estimated 4.1 kcal
      mol(-1) lower affinity with which TbetaRII binds TGFbeta2 as these three ligand
      residues are unchanged in TGFbeta1 but are conservatively substituted in TGFbeta2
      (Lys25, Ile92, and Lys94). To test this hypothesis, a TGFbeta2 variant was
      generated in which these three residues were changed to those in TGFbetas 1 and
      3. This variant exhibited receptor binding affinities comparable to those of
      TGFbetas 1 and 3. Together, these results show that these three residues underlie
      the lowered affinity of TGFbeta2 for TbetaRII and that all isoforms likely induce
      assembly of the TGFbeta signaling receptors in the same overall manner.

PMID- 16300790
TI  - Molecular structure of fd (f1, M13) filamentous bacteriophage refined with
      respect to X-ray fibre diffraction and solid-state NMR data supports specific
      models of phage assembly at the bacterial membrane.
AB  - Filamentous bacteriophage (Inovirus) is a simple and well-characterized model
      system. The phage particle, or virion, is about 60 angstroms in diameter and
      several thousand angstrom units long. The virions are assembled at the bacterial
      membrane as they extrude out of the host without killing it, an example of
      specific transport of nucleoprotein assemblages across membranes. The Ff group
      (fd, f1 and M13) has been especially widely studied. Models of virion assembly
      have been proposed based on a molecular model of the fd virion derived by X-ray
      fibre diffraction. A somewhat different model of the fd virion using solid-state
      NMR data has been proposed, not consistent with these models of assembly nor with
      the X-ray diffraction data. Here we show that reinterpreted NMR data are also
      consistent with the model derived from X-ray fibre diffraction studies, and
      discuss models of virion assembly.

PMID- 16300792
TI  - Analysis of non-fatal and fatal injury rates for mine operator and contractor
      employees and the influence of work location.
AB  - INTRODUCTION: Mining injury surveillance data are used as the basis for assessing
      the severity of injuries among operator and contractor employees in the
      underground and surface mining of various minerals. METHOD: Injury rates during
      1983-2002 derived from Mine Safety and Health Administration (MSHA) database are
      analyzed using the negative binomial regression model. The logarithmic mean
      injury rate is expressed as a linear function of seven indicator variables
      representing Non-Coal Contractor, Metal Operator, Non Metal Operator, Stone
      Operator, Sand and Gravel Operator, Coal Contractor, and Work Location, and a
      continuous variable, RelYear, representing the relative year starting with 1983
      as the base year. RESULTS: Based on the model, the mean injury rate declined at a
      1.69% annual rate, and the mean injury rate for work on the surface is 52.53%
      lower compared to the rate for work in the underground. With reference to the
      Coal Operator mean injury rate: the Non-Coal Contractor rate is 30.34% lower, the
      Metal Operator rate is 27.18% lower, the Non-Metal Operator rate is 37.51% lower,
      the Stone Operator rate is 23.44% lower, the Sand and Gravel Operator rate is
      16.45% lower, and the Coal Contractor rate is 1.41% lower. Fatality rates during
      the same 20 year period are analyzed similarly using Poisson regression model.
      Based on this model, the mean fatality rate declined at a 3.17% annual rate, and
      the rate for work on the surface is 64.3% lower compared to the rate for work in
      the underground. With reference to the Coal Operator mean fatality rate: the Non
      Coal Contractor rate is 234.81% higher, the Metal Operator rate is 5.79% lower,
      the Non-Metal Operator rate is 47.36% lower, the Stone Operator rate is 8.29%
      higher, the Sand and Gravel Operator rate is 60.32% higher, and the Coal
      Contractor rate is 129.54% higher.

PMID- 16300791
TI  - Computerized experience sampling method (ESMc): assessing feasibility and
      validity among individuals with schizophrenia.
AB  - The Experience Sampling Method (ESM) is an ecologically valid, time-sampling of
      self-reports developed to study the dynamic process of person-environment
      interactions. ESM with digital wristwatch and booklets (paper-based ESM; ESMp)
      has been used extensively to study schizophrenia. The present study is designed
      to test the feasibility and validity of using Computerized ESM (ESMc) among
      individuals with schizophrenia. ESMc is advantageous in allowing for recording of
      precise time-stamps of responses. We used PDAs ("Personal Digital Assistant";
      Palm handheld computers) to collect data on momentary psychotic symptoms, mood,
      and thoughts over a one day period among 10 hospitalized schizophrenia patients
      and 10 healthy controls. ESMc was equally acceptable to both groups, with similar
      ratings of comfort carrying the PDAs and operating them, interference with daily
      activities, as well as response rates. The schizophrenia patients reported
      significantly higher ratings of auditory and visual hallucinations,
      suspiciousness, sense of unreality, lack of thought control, fear of losing
      control, difficulty expressing thoughts, as well as depression/sadness,
      loneliness and less cheerfulness. Significant inverse relationships were found
      among both groups between ratings of feeling cheerful and being stressed,
      irritated, and sad/depressed. Among the schizophrenia subjects, the correlation
      between ratings of suspiciousness on ESMc and Scale for Assessment of Positive
      Symptoms (SAPS) approached significance, as well as the link between
      suspiciousness and stress. Our results support the feasibility and validity of
      using ESMc for assessment of momentary psychotic symptoms, mood, and experiences
      among individuals with schizophrenia. The authors discuss the potential
      applications of combining ESMc with ambulatory physiological measures.

PMID- 16300793
TI  - Backseat safety belt use and crash outcome.

PMID- 16300794
TI  - Development and implementation of a driver safety history indicator into the
      roadside inspection selection system.

PMID- 16300795
TI  - Egocentric path integration models and their application to desert arthropods.
AB  - Path integration enables desert arthropods to find back to their nest on the
      shortest track from any position. To perform path integration successfully,
      speeds and turning angles along the preceding outbound path have to be measured
      continuously and combined to determine an internal global vector leading back
      home at any time. A number of experiments have given an idea how arthropods might
      use allothetic or idiothetic signals to perceive their orientation and moving
      speed. We systematically review the four possible model descriptions of
      mathematically precise path integration, whereby we favour and elaborate the
      hitherto not used variant of egocentric cartesian coordinates. Its simple and
      intuitive structure is demonstrated in comparison to the other models. Measuring
      two speeds, the forward moving speed and the angular turning rate, and
      implementing them into a linear system of differential equations provides the
      necessary information during outbound route, reorientation process and return
      path. In addition, we propose several possible types of systematic errors that
      can cause deviations from the correct homeward course. Deviations have been
      observed for several species of desert arthropods in different experiments, but
      their origin is still under debate. Using our egocentric path integration model
      we propose simple error indices depending on path geometry that will allow future
      experiments to rule out or corroborate certain error types.

PMID- 16300796
TI  - Predicting epidemics on directed contact networks.
AB  - Contact network epidemiology is an approach to modeling the spread of infectious
      diseases that explicitly considers patterns of person-to-person contacts within a
      community. Contacts can be asymmetric, with a person more likely to infect one of
      their contacts than to become infected by that contact. This is true for some
      sexually transmitted diseases that are more easily caught by women than men
      during heterosexual encounters; and for severe infectious diseases that cause an
      average person to seek medical attention and thereby potentially infect health
      care workers (HCWs) who would not, in turn, have an opportunity to infect that
      average person. Here we use methods from percolation theory to develop a
      mathematical framework for predicting disease transmission through semi-directed
      contact networks in which some contacts are undirected-the probability of
      transmission is symmetric between individuals-and others are directed
      transmission is possible only in one direction. We find that the probability of
      an epidemic and the expected fraction of a population infected during an epidemic
      can be different in semi-directed networks, in contrast to the routine assumption
      that these two quantities are equal. We furthermore demonstrate that these
      methods more accurately predict the vulnerability of HCWs and the efficacy of
      various hospital-based containment strategies during outbreaks of severe
      respiratory diseases.

PMID- 16300797
TI  - Characteristics of acid extrusion from Chinese hamster ovary cells expressing
      different prostaglandin EP receptors.
AB  - Acid extrusion responses to prostaglandin E2 were investigated in Chinese hamster
      ovary (CHO) cells heterologously expressing human EP1, EP2, and EP3I receptors
      (hEP1, hEP2 and hEP3I) by using a microphysiometer that detected small pH changes
      in the extracellular microenvironment. In the cells expressing hEP1, which is
      known to increase intracellular Ca2+, prostaglandin E2 (1 and 10 nM) slowly
      accelerated acid extrusion, but at higher concentrations an initial transient
      phase (approximately 5 times greater than the basal acidification) overlapped the
      slowly developing phase. In contrast, the cells expressing hEP2, which evokes
      cAMP production, showed dual responses to prostaglandin E2: an initial reduction
      followed by an acceleration of acid extrusion. In the cells expressing hEP3I,
      which is known to produce both a decrease in cAMP and a modest increase in
      intracellular Ca2+, acid extrusion was gradually accelerated by prostaglandin E2
      and reached a plateau at around 2 min. Elimination of extracellular Ca2+
      diminished the responses to prostaglandin E2 in hEP1 cells, but had little effect
      on the responses in hEP2 and hEP3I cells. Forskolin mimicked the dual effects of
      prostaglandin E2 observed in the hEP2 cells. Pretreatment with pertussis toxin
      inhibited the response to prostaglandin E2 in hEP3I cells, but the responses in
      hEP1 and hEP2 cells were not affected. Na+/H+ exchanger (NHE) inhibitors (EIPA
      and HOE642) suppressed all the responses induced by prostaglandin E2 in hEP1,
      hEP2, and hEP3I cells. These results suggest that EP receptor subtypes regulate
      acid extrusion mainly via NHE-1 through distinct signal transduction pathways in
      CHO cells.

PMID- 16300798
TI  - Transcriptional regulation of vascular bone morphogenetic protein by endothelin
      receptors in early autoimmune diabetes mellitus.
AB  - Endothelin (ET) and bone morphogenic proteins (BMP) have been implicated in the
      development of micro- and macrovascular complications of type 2 diabetes mellitus
      due to atherosclerosis. This study investigated vascular BMP-expression during
      early development of experimental autoimmune diabetes mellitus and whether ET(A)
      receptors are involved in its regulation, using the selective ET(A) receptor
      antagonist BSF461314. Specificity of BSF461314 was confirmed through ET-mediated
      p44/42 mitogen-activated protein kinase (ERK1/2) phosphorylation experiments. For
      animal studies, non-obese diabetic (NOD) and control mice at 16 weeks of age were
      treated with BSF461314 for 6 weeks. Plasma glucose levels were measured before
      and after treatment and vascular gene expression of BMP-2, BMP-7, and BMP-type II
      receptor was determined in the aorta by quantitative real-time polymerase chain
      reaction analysis. At the beginning of the study in all animals, plasma glucose
      levels were within the normal range. After 6 weeks gene expression of vascular
      BMP-2, BMP-7 and BMP-type II receptor was almost doubled in NOD mice compared
      with non-diabetic controls (p < 0.05). Concomitant treatment with BSF461314
      significantly reduced expression of all BMPs and lowered plasma glucose levels in
      NOD mice close to controls (all p < 0.05 versus untreated). In conclusion,
      vascular BMP-2, BMP-7, and BMP-type II receptor expression is upregulated in
      early stages of autoimmune diabetes mellitus. The data further indicate that
      ET(A) receptors inhibit diabetes-associated activation of vascular BMPs and
      regulate plasma glucose levels suggesting that ET(A) receptors might provide a
      new therapeutic target to interfere with the early development of atherosclerosis
      in patients with type 1 diabetes mellitus.

PMID- 16300799
TI  - Adenosine receptor-mediated coronary vascular protection in post-ischemic mouse
      heart.
AB  - This study evaluated the ability of A1 and A3 adenosine receptor (AR) agonism,
      and A1, A2A, A2B and A3AR antagonism (revealing "intrinsic" responses), to modify
      post-ischemic coronary dysfunction in mouse heart. Vascular function was assessed
      before and after 20 min global ischemia and 30-45 min reperfusion in Langendorff
      perfused C57/Bl6 mouse hearts. Ischemic insult impaired coronary sensitivity to
      the endothelial-dependent dilators ADP (pEC50=6.8+/-0.1 vs. 7.6+/-0.1, non
      ischemic) and acetylcholine (pEC50=6.1+/-0.1 vs. 7.3+/-0.1 in non-ischemic), and
      for the mixed endothelial-dependent/independent dilator 2-chloroadenosine
      (pEC50=7.5+/-0.1 vs. 8.4+/-0.1, non-ischemic). Endothelium-independent dilation
      in response to nitroprusside was unaltered (pEC50=7.0+/-0.1 vs. 7.1+/-0.1 in non
      ischemic). Pre-treatment with a selective A1AR agonist (50 nM CHA) failed to
      modify coronary dysfunction, whereas A1AR antagonism (200 nM DPCPX) worsened the
      effects of I/R (2-chloroadenosine pEC50=6.9+/-0.1). Conversely, A3AR agonism (100
      nM Cl-IB-MECA) did reduce effects of I/R (pEC50s=8.0+/-0.1 and 7.3+/-0.1 for 2
      chloroadenosine and ADP, respectively), whereas antagonism (100 nM MRS1220) was
      without effect. While A2AAR agonism could not be assessed (due to pronounced
      vasodilatation), A2AAR antagonism (100 nM SCH58261) was found to exert no effect,
      and antagonism of A2BARs (50 nM MRS1754) was also ineffective. The protective
      actions of A3AR agonism were also manifest as improved reactive hyperemic
      responses. Interestingly, post-ischemic coronary dysfunction was also limited by:
      Na+-H+ exchange (NHE) inhibition with 10 or 50 microM BIIB-513 (2-chloroadenosine
      pEC50s=7.8+/-0.1, either dose), an effect not additive with A3AR agonism; Ca2+
      antagonism with 0.3 microM verapamil (2-chloroadenosine pEC50=7.9+/-0.1); and
      Ca2+ desensitization with 5 mM BDM (2-chloroadenosine pEC50=7.8+/-0.1). In
      contrast, endothelin antagonism (200 nM PD142893) and anti-oxidant therapy (300
      microM MPG+150 U/ml SOD+600 U/ml catalase) were ineffective. Our data
      collectively confirm that ischemia selectively impairs endothelial function and
      reactive hyperemia independently of blood cells. Vascular injury is intrinsically
      limited by endogenous (but not exogenous) activation of A1ARs, whereas exogenous
      A3AR activation further limits dysfunction (improving post-ischemic
      vasoregulation). Finally, findings suggest this form of post-ischemic coronary
      injury is unrelated to endothelin or oxidant stress, but may involve modulation
      of Ca2+ overload and/or related ionic perturbations.

PMID- 16300800
TI  - The occurrence of the cold-water coral Lophelia pertusa (Scleractinia) on oil and
      gas platforms in the North Sea: colony growth, recruitment and environmental
      controls on distribution.
AB  - This study reports a newly established sub-population of Lophelia pertusa, the
      dominant reef-framework forming coral species in the north-east Atlantic, on oil
      and gas platforms in the northern North Sea. L. pertusa was positively identified
      on 13 of 14 platforms examined using existing oil and gas industry visual
      inspections. Two platforms were inspected in more detail to examine depth and
      colony size distributions. We recorded 947 colonies occurring between 59 and 132
      m depth that coincides with cold Atlantic water at depths below the summer
      thermocline in the northern North Sea. We suggest that these colonies provide
      evidence for a planktonic larval stage of L. pertusa with recruits initially
      originating from populations in the north-east Atlantic and now self recruiting
      to the platforms. Size class distribution showed a continuous range of size
      classes, but with few outlying large colonies. The break between the largest
      colonies and the rest of the population is considered as the point when colonies
      began self recruiting to the platforms, resulting in greater colonization
      success. We present the first documented in situ colony growth rate estimate (26
      +/- 5 mm yr(-1)) for L. pertusa based on 15 colonies from the Tern Alpha platform
      with evidence for yearly recruitment events starting the year the platform was
      installed. Evidence of contamination from drill muds and cuttings was observed on
      the Heather platform but appeared limited to regions close to drilling discharge
      points, where colonies experience partial as well as whole colony mortality.

PMID- 16300801
TI  - The effect of the "Prestige" oil spill on the plankton of the N-NW Spanish coast.
AB  - Chlorophyll, primary production, zooplankton biomass and the species composition
      of phytoplankton and zooplankton were studied in 2003, after the Prestige
      shipwreck. The information obtained was compared to previous data series
      available for the area affected by the spill. A large data series on plankton
      variables for the N-NW Spanish coast existed, and therefore a realistic
      evaluation of the effects by comparison with the range of natural variability
      could be carried out. We emphasized the evaluation of impact during the spring
      bloom, the first important biological event after the spill. Some minor changes
      were observed occasionally, but they did not show any clear pattern and were more
      related to the natural variability of the ecosystem than to effect of the spill.
      Plankton community structure did not undergo any changes. Only a few species were
      more abundant during spring 2003 than in previous years. No significant changes
      were detected in the planktonic community during productive periods, such as the
      spring bloom and the summer blooms related to intrusions of East North Atlantic
      Central Waters. The lack of evidence of the effects of the spill on planktonic
      communities is discussed in terms of the characteristics of the fuel, the high
      dynamics of the water masses, the biological mechanisms through which the fuel
      from the surface waters is transferred to the sea floor and, particularly, the
      influence of the natural variability by means of large and meso-scale
      hydrographic processes in the area under study. At the present time it is not
      possible to determine any minor effects the spill may have had on the plankton
      owing to the great variability of the planktonic cycles and the short-term impact
      of the oil from the Prestige on the pelagic system.

PMID- 16300802
TI  - Nitrogen isotope ratios in estuarine biota collected along a nutrient gradient in
      Narragansett Bay, Rhode Island, USA.
AB  - Stable nitrogen isotope ratios were used to study the incorporation of
      anthropogenically-derived nitrogen into the food webs of salt marsh systems along
      a contamination gradient in Narragansett Bay. Nitrogen isotope ratios
      (delta(15)N) were measured in six estuarine species collected from three marshes
      along this gradient, monthly from June to October between 1997 and 1999. A
      significant decrease in delta(15)N was found with distance along the estuary for
      four of the six species. Significant differences were found among monthly isotope
      ratios for some species. Nitrogen isotope ratios in sea lettuce (Ulva lactuca)
      increased during the summer season with highest delta(15)N values measured during
      September and October. This trend was most pronounced at the station receiving
      the highest nutrient inputs. Elevated delta(15)N values at this station appeared
      to correlate with seawater ammonia/nitrate concentration ratios. The temporal
      variations in delta(15)N suggest that care should be taken in species selection
      and the design of sampling schemes of studies using delta(15)N for monitoring
      anthropogenic nutrients in aquatic systems. Sampling programs designed to
      determine long-term trends should consider species that do not show rapid
      fluctuations in isotope ratios. The mud snail, Nassarius obsoletus, responded
      this way in the present study. Studies designed to measure short-term changes
      should include species such as U. lactuca, which rapidly respond to isotope
      changes. The results from this study also help to establish a baseline for
      nitrogen isotope values in Narragansett Bay. This information can be used to
      monitor future trends in nitrogen inputs to this estuary.

PMID- 16300803
TI  - The effects of acute and long-term lithium treatments on trkB neurotrophin
      receptor activation in the mouse hippocampus and anterior cingulate cortex.
AB  - As brain-derived neurotrophic factor (BDNF) and its receptor trkB are linked to
      the etiology and treatment of mood disorders, we examined the effects of acute
      and long-term treatment of mood-stabilizer lithium on trkB activation and
      signaling and BDNF levels in the mouse anterior cingulate cortex (AC) and
      hippocampus (HC). The trkB activity was measured using specific antibodies
      against the phosphorylated trkB catalytic domain (pY705/6) and the shc binding
      site (pY515). In the AC, both acute and long-term LiCl treatment enhanced the
      pY705/6 of trkB. In contrast, acute or long-term LiCl treatment did not
      significantly alter the pY705/6 of trkB in the HC. Interestingly, however, acute
      LiCl treatment significantly reduced the phosphorylation of cAMP related element
      binding protein (CREB), a major intracellular target of trkB, in the HC.
      Moreover, pY515 of trkB in the AC and HC was not altered by any of the treatment.
      Also, prolonged LiCl treatment had no significant effects on BDNF levels or CREB
      activation in either the AC or HC. The present results suggest that acute and
      long-term lithium treatment induces trkB activation in the AC but not in the HC.
      The activation of CREB is, however, significantly reduced in the HC after acute
      LiCl treatment.

PMID- 16300804
TI  - The posterior parietal cortex: sensorimotor interface for the planning and online
      control of visually guided movements.
AB  - We present a view of the posterior parietal cortex (PPC) as a sensorimotor
      interface for visually guided movements. Special attention is given to the role
      of the PPC in arm movement planning, where representations of target position and
      current hand position in an eye-centered frame of reference appear to be mapped
      directly to a representation of motor error in a hand-centered frame of
      reference. This mapping is direct in the sense that it does not require target
      position to be transformed into intermediate reference frames in order to derive
      a motor error signal in hand-centered coordinates. Despite being direct, this
      transformation appears to manifest in the PPC as a gradual change in the
      functional properties of cells along the ventro-dorsal axis of the superior
      parietal lobule (SPL), i.e. from deep in the sulcus to the cortical surface.
      Possible roles for the PPC in context dependent coordinate transformations,
      formation of intrinsic movement representations, and in online control of
      visually guided arm movements are also discussed. Overall these studies point to
      the emerging view that, for arm movements, the PPC plays a role not only in the
      inverse transformations required to convert sensory information into motor
      commands but also in 'forward' transformations as well, i.e. in integrating
      sensory input with previous and ongoing motor commands to maintain a continuous
      estimate of arm state that can be used to update present and future movement
      plans. Critically, this state estimate appears to be encoded in an eye-centered
      frame of reference.

PMID- 16300805
TI  - Revisiting unilateral neglect.
AB  - Unilateral neglect, a neurological disorder in which patients fail to detect or
      respond to contralesional stimuli, has long been considered a failure of
      attentional orienting mechanisms. This review provides a selective overview of
      the prominent biases in spatial orienting and exploratory motor behaviour
      observed in these patients before considering the impact of other factors on the
      presentation of the disorder and how those factors might inform current
      neurological models of neglect. In the latter part of the review, we intend to
      suggest that neglect is likely to be a combination of distinct but interacting
      impairments including biases in attentional orienting, exploratory motor
      behaviours and a deficit of spatial working memory. That is, we suggest that the
      cardinal symptom of neglect - a loss of awareness for contralesional stimuli and
      events - arises as a result of a combination of these impairments rather than
      being associated solely with the more dramatic and immediately evident biases in
      spatial attention.

PMID- 16300806
TI  - Brain areas involved in spatial working memory.
AB  - Spatial working memory entails the ability to keep spatial information active in
      working memory over a short period of time. To study the areas of the brain that
      are involved in spatial working memory, a group of stroke patients was tested
      with a spatial search task. Patients and healthy controls were asked to search
      through a number of boxes shown at different locations on a touch-sensitive
      computer screen in order to find a target object. In subsequent trials, new
      target objects were hidden in boxes that were previously empty. Within-search
      errors were made if a participant returned to an already searched box; between
      search errors occurred if a participant returned to a box that was already known
      to contain a target item. The use of a strategy to remember the locations of the
      target objects was calculated as well. Damage to the right posterior parietal and
      right dorsolateral prefrontal cortex impaired the ability to keep spatial
      information 'on-line', as was indicated by performance on the Corsi Block-Tapping
      task and the within-search errors. Moreover, patients with damage to the right
      posterior parietal cortex, the right dorsolateral prefrontal cortex and the
      hippocampal formation bilaterally made more between-search errors, indicating the
      importance of these areas in maintaining spatial information in working memory
      over an extended time period.

PMID- 16300807
TI  - Early life host-bacteria relations and development: long-term individual
      differences in neuroimmune function following neonatal endotoxin challenge.
AB  - Neonatal animals have a proportionately greater risk, relative to the adult
      animal, of developing a bacterial infection. Research has revealed that such
      infections can influence biological processes long after the actual infection has
      been resolved. Indeed, studies examining the long-term alterations induced by
      early-life infection, simulated using endotoxin, have indicated that some aspects
      of the systemic inflammatory response in the adult animal are susceptible to
      modification. Available evidence suggests that altered inflammatory activities
      observed in the neonatally endotoxin challenged adult may be the result of
      potentiated hypothalamic pituitary adrenal (HPA) activity, specifically increased
      corticosterone production. Few studies, however, have examined whether altered
      corticosterone production is actually associated with changes in systemic
      inflammation in the neonatally endotoxin challenged adult animal. The aim,
      therefore, of the current study was to simultaneously examine the relationship
      between altered inflammatory activities and corticosterone production in the
      neonatally endotoxin challenged adult rat. Our findings demonstrate no
      significant differences exist between adults neonatally treated with saline or
      endotoxin in terms of their production of corticosterone following endotoxin
      challenge. While not appearing to influence the production of corticosterone
      neonatal endotoxin challenge did result in a marked attenuation in the adult's
      febrile response following endotoxin challenge. Interestingly, circulating levels
      of IL-1beta and TNF-alpha were found to be equivalent in neonatal treatment
      groups following endotoxin administration in adulthood, indicating that the
      reduction in fever was unlikely to be the result of altered pro-inflammatory
      cytokine production. Further, no differences were found between neonatal
      treatment groups in net food consumption, water consumption or weight loss
      following endotoxin challenge in adulthood. Collectively, these findings
      demonstrate that neonatal endotoxin challenge does not affect a blanket down
      regulation of inflammatory processes but rather appears to induce highly specific
      alterations in the adult male Fischer-344 rat.

PMID- 16300808
TI  - A competitive effect of androgen signaling on male mouse attraction to volatile
      female mouse odors.
AB  - Olfaction plays an important role in animal communication. We hypothesized that
      males recognize the attractive volatile odors attributed to female reproductive
      ability. We measured the period during which a male mouse spent sniffing volatile
      odors from a sham-operated female mouse or an ovariectomized mouse without visual
      or tactile contact. Intact male mice spent more time sniffing volatile odors from
      proestrous, estrous or metestrous females than from ovariectomized females. There
      was no difference in castrated male mice. To investigate the involvement of
      sexual hormone in this behavior, castrated male mice were treated with 17 alpha
      estradiol (E), dihydrotestosterone (DHT), or both. E-treatment did not affect
      sniffing behavior. Regardless of the estrous stages, DHT-treated castrated males
      spent less time sniffing the volatile odors from sham-operated than from
      ovariectomized female mice. Both E- and DHT-treated castrated males spent less
      time sniffing the volatile odors from proestrous or estrous females than from
      ovariectomized females. These results suggest that neither androgen nor estrogen
      is sufficient for reproducing male attraction to volatile female mouse odors, and
      that androgen signaling has a competitive effect against the attraction.

PMID- 16300809
TI  - Alkaloids from Oriciopsis glaberrima Engl. (Rutaceae).
AB  - Two alkaloid derivatives, oriciacridone A and B, were isolated from the stem bark
      of Oriciopsis glaberrima (Rutaceae). The structures were elucidated by a detailed
      spectroscopic analysis. The extract exhibited in vitro significant antimicrobial
      activity against a range of micro-organisms.

PMID- 16300810
TI  - Transition state analysis of adenosine nucleosidase from yellow lupin (Lupinus
      luteus).
AB  - The transition state of adenosine nucleosidase (EC 3.2.2.7) isolated from yellow
      lupin (Lupinus luteus) was determined based upon a series of heavy atom kinetic
      isotope effects. Adenosine labeled with 13C, 2H, and 15N was analyzed by liquid
      chromatography/electrospray mass spectrometry to determine kinetic isotope
      effects. Values of 1.024+/-0.004, 1.121+/-0.005, 1.093+/-0.004, 0.993+/-0.006,
      and 1.028+/-0.005 were found for [1'-13C], [1'-2H], [2'-2H], [5'-2H], and [9-15N]
      adenosine, respectively. Using a bond order bond energy vibrational analysis, a
      transition state consisting of a significantly broken C-N bond, formation of an
      oxocarbenium ion in the ribose ring, a conformation of C3-exo for the ribose
      ring, and protonation of the heterocyclic base was proposed. This transition
      state was found to be very similar to the transition state for nucleoside
      hydrolase, another purine metabolizing enzyme, isolated from Crithidia
      fasciculata.

PMID- 16300811
TI  - Isolation and chemotaxonomic significance of tuberostemospironine-type alkaloids
      from Stemona tuberosa.
AB  - An alkaloid named 6alpha-hydroxycroomine (1) as well as the known croomine (2),
      both belonging to the tuberostemospironine-alkaloid type, were isolated from
      Stemona tuberosa as the major components. The structure of 1 was elucidated
      through extensive spectroscopic analyses. Comparison of the HPLC profiles of the
      total alkaloids and the crude methanol extract showed that both compounds are
      naturally occurring. The first isolation of 1 and 2 from S. tuberosa has
      chemotaxonomic significance, confirming the close relationship between Stemona
      and Croomia. The trnL sequences of plants from the four genera of Stemonaceae
      cluster together as a clade, further lending support to retaining them in a
      single family.

PMID- 16300812
TI  - Regeneration of the replication-associated proteins tandem direct repeat
      recognition nucleotide sequence at the origin of DNA replication of porcine
      circovirus type 1.
AB  - Four copies of a hexanucleotide (H) sequence are located to the right of the
      palindrome at the origin of DNA replication of the porcine circovirus type 1
      (PCV1) genome. These sequences are organized in two direct tandems, the proximal
      H1/H2 and the distal H3/H4 repeats, and they have been shown to be binding sites
      for the essential Rep and Rep' proteins. Previous work demonstrated that
      infectious PCV1 virion can accommodate a variable number of H sequences at the
      origin of DNA replication. In this work, mutational analysis was conducted to
      elucidate the critical core element within the hexanucleotide with respect to
      self-DNA replication and progeny virus synthesis. It was found that while a
      single H sequence abutting the palindrome is sufficient for PCV1 viability, a
      tandem repeat arrangement is the more stable and thus preferred configuration.
      Within the H sequence, selected nucleotides at specific positions are critical
      for Rep-associated protein recognition and for viral DNA replication.

PMID- 16300813
TI  - Individual contributions of the human metapneumovirus F, G, and SH surface
      glycoproteins to the induction of neutralizing antibodies and protective
      immunity.
AB  - We evaluated the individual contributions of the three surface glycoproteins of
      human metapneumovirus (HMPV), namely the fusion F, attachment G, and small
      hydrophobic SH proteins, to the induction of serum HMPV-binding antibodies, serum
      HMPV-neutralizing antibodies, and protective immunity. Using reverse genetics,
      each HMPV protein was expressed individually from an added gene in recombinant
      human parainfluenza virus type 1 (rHPIV1) and used to infect hamsters once or
      twice by the intranasal route. The F protein was highly immunogenic and
      protective, whereas G and SH were only weakly or negligibly immunogenic and
      protective, respectively. Thus, in contrast to other paramyxoviruses, the HMPV
      attachment G protein is not a major neutralization or protective antigen. Also,
      although the SH protein of HMPV is a virion protein that is much larger than its
      counterparts in previously studied paramyxoviruses, it does not appear to be a
      significant neutralization or protective antigen.

PMID- 16300814
TI  - Diverse suppressors of RNA silencing enhance agroinfection by a viral replicon.
AB  - Launching the Beet yellows virus (BYV) minireplicon by agrobacterial delivery
      resulted in an unexpectedly low number of infected cells per inoculated leaf.
      This effect was due to a strong RNA silencing response in the agroinfiltrated
      leaves. Strikingly, ectopic co-expression of p21, a BYV RNA silencing suppressor,
      increased minireplicon infectivity by three orders of magnitude. Mutational
      analysis demonstrated that this effect correlates with suppressor activity of
      p21. Five diverse, heterologous viral suppressors were also active in this
      system, providing a useful approach for a dramatic, up to 10,000-fold, increase
      of the efficiency of agroinfection. The minireplicon agroinfection assay was also
      used to identify a new suppressor, a homolog of BYV p21, derived from Grapevine
      leafroll-associated virus-2. In addition, we report preliminary data on the
      suppressor activity of the p10 protein of Grapevine virus A and show that this
      protein belongs to a family of Zn-ribbon-containing proteins encoded by
      filamentous plant RNA viruses from three genera. The members of this family are
      predicted to have RNA silencing suppressor activity.

PMID- 16300815
TI  - Illusory motion induced by the offset of stationary luminance-defined gradients.
AB  - An illusory motion induced by the offset of a stationary gradient stimulus is
      characterized. When a gradient stimulus, whose luminance contrast ranges
      gradually from white on one side to black on the other, is made to disappear all
      at once so that only the uniform white background remains visible, illusory
      motion is perceived. This motion lasts approximately 700 ms, as if the stimulus
      moves from the low to the high luminance contrast side. This gradient-offset
      induced motion does not occur for equiluminant color-defined gradient offsets,
      suggesting that it relies mainly on the magnocellular pathway. Our data are
      consistent with the hypothesis that this illusion is caused by the decay of the
      gradient afterimage.

PMID- 16300816
TI  - Optimizing experimental design to estimate ammonia and nitrite oxidation
      biokinetic parameters from batch respirograms.
AB  - Knowledge of relative NH(4+)-N to NO(2-)-N oxidation and NO(2-)-N to NO(3-)-N
      oxidation dynamics is essential before application of either single-step or two
      step nitrification models to fit batch nitrification respirograms. We have
      previously shown that two step nitrification models based on respirometry permit
      the estimation of kinetic parameters for both nitrification steps from a single
      respirogram associated with NH(4+)-N to NO(3-)-N oxidation. However, two-step
      model parameter estimates are meaningful only under circumstances when the
      respirograms contain sufficient kinetic information pertaining to both steps. In
      this study, we present an operationally amenable extant batch nitrification
      respirometric assay to engender maximal information content in the resulting
      respirograms with respect to both constituent nitrification steps. The developed
      design consists of an initial NH(4+)-N pulse to a nitrifying biomass sample
      followed by an additional NO(2-)-N pulse at an optimal time point, which can be
      rigorously determined by maximizing the value of the determinant of the Fisher
      information matrix, Det(F) or, alternatively, by visually identifying the point
      of NH(4+)-N depletion during the respirometric assay. The proposed design is
      applicable for accurate determination of the Monod kinetic parameter estimates
      for both nitrification steps from batch respirograms even when the pseudo-first
      order rate coefficients for the two nitrification steps are nearly equal; a
      condition under which standard NH(4+)-N to NO(3-)-N respirograms typically lack
      information with respect to NO(2-)-N oxidation.

PMID- 16300817
TI  - Variation in modern human enamel formation times.
AB  - Most of what we know about the timing of human enamel formation comes from
      radiographic studies on children of known age. Here, we present new longitudinal
      data derived from a histological analysis of tooth enamel. Two samples, one from
      southern Africa and one from northern Europe, contained all anterior and molar
      tooth types. Two further samples contained only one tooth type: canines from a
      medieval Danish sample and third molars from a modern North American sample. Data
      were collected on 326 molars and 352 anterior teeth. Each tooth was sectioned and
      prepared for polarized light microscopy. We used daily enamel cross striations to
      determine cuspal enamel formation time, recorded the periodicity of long-period
      striae in the lateral enamel, and used this value to calculate enamel formation
      times for each decile of crown length. We present data that reveal some of the
      processes whereby differences in enamel formation times arise between our
      samples. Mean cuspal enamel formation times were similar in southern African and
      northern European anterior teeth, but differed in certain molar cusps. All the
      southern African anterior teeth completed enamel formation earlier. The greatest
      difference in mean chronological age at enamel completion was 5.2 vs. 6.2 years
      of age in lower canines. However, enamel completion times in the molar teeth
      showed few differences between the samples, with mean times for the longest
      forming cusps all falling between 3.0 years and 3.45 years. Our data suggest
      fewer differences between samples and smaller ranges of variation than in many
      radiographic studies and present a more realistic picture of worldwide variation
      in enamel formation times.

PMID- 16300818
TI  - Comparisons of low-cost adsorbents for treating wastewaters laden with heavy
      metals.
AB  - In this article, the removal performance and cost-effectiveness of various low
      cost adsorbents derived from agricultural waste, industrial by-product or natural
      material are evaluated and compared to those of activated carbon for the removal
      of heavy metals (Cd(II), Cr(III), Cr(VI), Cu(II), Ni(II) and Zn(II)) from metals
      contaminated wastewater. To highlight their technical applicability, selected
      information on pH, dose required, initial metal concentration, adsorption
      capacity and the price of the adsorbents is presented. It is evident from the
      survey of 102 published studies (1984-2005) that low cost adsorbents derived from
      agricultural waste have demonstrated outstanding capabilities for the removal of
      heavy metal (Cr(VI): 170 mg/g of hazelnut shell activated carbon, Ni(II): 158
      mg/g of orange peel, Cu(II): 154.9 mg/g of soybean hull treated with NaOH and
      citric acid, Cd(II): 52.08 mg/g of jackfruit), compared to activated carbon
      (Cd(II): 146 mg/g, Cr(VI): 145 mg/g, Cr(III): 30 mg/g, Zn(II): 20 mg/g).
      Therefore, low-cost adsorbents can be viable alternatives to activated carbon for
      the treatment of metals-contaminated wastewater. It is important to note that the
      adsorption capacities presented in this paper vary, depending on the
      characteristics of the individual adsorbent, the extent of surface modification
      and the initial concentration of the adsorbate. In general, technical
      applicability and cost-effectiveness are the key factors that play major roles in
      the selection of the most suitable adsorbent to treat inorganic effluent.

PMID- 16300819
TI  - Ovarian metastasis in carcinoma of the uterine cervix.
AB  - BACKGROUND: The present study was conducted to determine the frequency and
      clinicopathological features of ovarian metastasis in a large population of
      patients with stage Ib-IIb cervical cancer. METHODS: The study population
      consisted of 3471 patients with stage Ib to IIb cervical cancer who underwent
      radical hysterectomy, including pelvic lymphadenectomy and bilateral salpingo
      oophorectomy, at our six institutions between 1981 and 2000. To our knowledge,
      this study is the largest review of patients with ovarian metastasis from
      cervical cancer. We reviewed the patients' medical records to determine
      clinicopathological features. RESULTS: Fifty-two patients (1.50%) had ovarian
      metastases: 6 in stage Ib1, 12 in stage Ib2, 5 in stage IIa, and 29 in stage IIb.
      The mean age of patients with ovarian metastasis was 49.9 years (range: 29-73
      years). The incidence of ovarian metastasis in patients with cervical cancer was
      0.22% for stage Ib, 0.75% for stage IIa, and 2.17% for stage IIb with squamous
      cell carcinoma, and 3.72%, 5.26%, and 9.85%, respectively, in adenocarcinoma.
      Ovarian metastasis occurred more frequently among patients with adenocarcinoma
      than among those with squamous cell carcinoma (5.31% vs. 0.79%). Outcome for
      patients with ovarian metastasis was very poor and not related to FIGO stage and
      histological type. The presence of ovarian metastasis did not correlate with
      lymph node involvement or parametrial invasion. CONCLUSION: Study results
      indicate that ovaries can be preserved in patients with stage Ib-IIa squamous
      cell carcinoma but removed in all patients with adenocarcinoma.

PMID- 16300820
TI  - Insulin-like growth factor receptor I targeting in epithelial ovarian cancer.
AB  - OBJECTIVES: Preclinical evaluation of the anti-neoplastic activity of an insulin
      like growth factor I receptor (IGF-IR) kinase inhibitor in ovarian cancer.
      METHODS: The OVCAR-3 and OVCAR-4 cell lines were investigated under serum-free
      tissue culture conditions. IGF-I and IGF-II production were evaluated by standard
      ELISA and immunohistochemistry. IGF-IR expression and protein levels were
      evaluated by Western blotting. Cytotoxicity assays were performed in triplicates
      using the Alamar colorimetric assay. Apoptosis was evaluated by flow cytometry
      and by Western blotting for PARP. RESULTS: The OVCAR-3 and OVCAR-4 cell lines
      produce IGF-I and IGF-II, and express IGF-IR, detectable by Western blotting,
      supporting the existence of an autocrine loop. The existence of this loop
      justified studies of NVP-AEW541, a small molecular weight inhibitor of the IGF-IR
      kinase. We observed growth inhibition of the ovarian cancer cell lines, with IC50
      between 5 and 15 microM. We also observed that NVP-AEW541 sensitized cells to
      cisplatin in vitro. Western blotting demonstrated that NVP-AEW541 induced
      apoptosis at the concentrations that were used in the cytotoxicity assays, and
      decreased the concentration of the phosphorylated AKT signaling protein
      downstream of the IGF-IR. CONCLUSIONS: IGF-IR is a potential new molecular target
      in ovarian cancer. The anti-neoplastic activity of NVP-AEW541 in ovarian cancer
      was observed at concentrations higher than those previously reported for multiple
      myeloma, suggesting the possibility that a portion of the observed anti
      neoplastic activity could involve targets other than the IGF-IR. Experiments are
      being conducted to investigate the cytotoxicity profile in vivo and the clinical
      relevance of NVP-AEW541 in ovarian cancer treatment.

PMID- 16300821
TI  - Integration of HPV-16 and HPV-18 DNA in vulvar intraepithelial neoplasia.
AB  - OBJECTIVE: Vulvar intraepithelial neoplasia (VIN) is a premalignant disease of
      the lower genital tract. The increased occurrence of high-risk human
      papillomavirus (HPV) infection seems to be associated with the increasing
      frequency of VIN. Integration of HPV DNA into host chromosome has been
      hypothesized to be a critical step in the carcinogenesis of cervical neoplasia
      resulting in altered expression of two viral transforming genes E6 and E7.
      METHOD: We analyzed HPV-16 and HPV-18 DNA, and integrated transcripts of HPV-16
      and HPV-18 genomes in 30 VIN cases with 53 lesions using a PCR-based protocol for
      the amplification of papillomavirus oncogene transcripts (APOT). RESULT: 24 of 30
      VIN lesions (80%) harbored HPV-16 (in 23 cases) and HPV-18 DNA. Integration of
      HPV-16 and HPV-18 genome was observed in eight (38.1%) of 21 HPV-16/18 positive
      VIN III cases. All eight VIN were multifocal and had multicentric disease
      (CIN/VAIN) including one case that progressed to vulvar carcinoma. Five of eight
      lesions were found to have E7 specific viral-cellular fusion transcripts only,
      two of eight showed E7-E4 viral-cellular fusion transcripts, and one of eight had
      both episomally derived and E7-E4 viral-cellular fusion transcripts. In 10
      (83.3%) of 12 multifocal VIN III patients, all specimens derived from the same
      patient harbored the same HPV type and HPV transcript pattern suggesting
      monoclonality. CONCLUSION: HPV-16 is the most prevalent type among VIN II/III.
      HPV-16 and HPV-18 DNA integration into host cell genome seems to be related to
      the progression stage of vulvar dysplasia and, therefore, may be necessary for
      development of HPV-associated invasive vulvar carcinoma.

PMID- 16300822
TI  - Primary and metastatic mucinous adenocarcinomas of the ovary: Evaluation of the
      diagnostic approach using tumor size and laterality.
AB  - OBJECTIVE: To evaluate the usefulness of the recently proposed algorithm (Seidman
      JD, Kurman RJ, Ronnett BM. Primary and metastatic mucinous adenocarcinomas in the
      ovaries: incidence in routine practice with a new approach to improve
      intraoperative diagnosis. Am J Surg Pathol 2003; 27: 985-93 [5]) that classifies
      mucinous adenocarcinomas of the ovary as primary when they were unilateral > or
      =10 cm and as metastatic when they were unilateral <10 cm or bilateral. METHODS:
      Malignant ovarian neoplasms, which were resected in Chiang Mai University
      Hospital between 1992 and 2003, were histologically reviewed. Mucinous
      adenocarcinomas involving the ovary were identified. The medical records and
      radiologic materials were reviewed in correlation with the pathologic features to
      identify the primary site. RESULTS: There were 74 cases of mucinous
      adenocarcinomas; 16 were primary ovarian; 52, metastatic; and 6 of indeterminate
      primary site (primary versus metastatic). Primary mucinous adenocarcinomas had a
      mean size of 16.4 cm and bilateral involvement in 13%. Metastatic mucinous
      adenocarcinomas had a mean size of 11.7 cm and bilateral involvement in 77%.
      Excluding the 6 tumors of indeterminate primary site, the proposed algorithm
      correctly classified primary and metastatic tumors in 84% of 68 cases. Of 21
      unilateral mucinous adenocarcinomas > or =10 cm, 62% were primary ovarian. Of 5
      unilateral tumors <10 cm, 80% were metastatic. Of 42 bilateral mucinous
      adenocarcinomas, 95% were metastatic. CONCLUSION: The algorithm provided high
      accuracy in the overall prediction of primary and metastatic mucinous
      adenocarcinomas of the ovary, with major strength in the identification of
      metastatic tumors by bilaterality or size <10 cm. However, the prediction of
      primary mucinous adenocarcinomas by unilaterality and size > or =10 cm was less
      reliable than previously reported. Due to the overlapping features between
      primary and metastatic tumors and the higher frequency of the latter, the
      possibility of metastases should always be borne in mind in the evaluation of
      mucinous adenocarcinomas of the ovary.

PMID- 16300823
TI  - Can a handwashing intervention make a difference? Results from a randomized
      controlled trial in Jerusalem preschools.
AB  - BACKGROUND: Preschools are often focal points for the spread of illness among
      young children. The objective of this preschool intervention trial was to
      determine whether a hygiene program can promote handwashing and thereby reduce
      illness absenteeism. METHODS: This cluster randomized trial included 40 Jerusalem
      preschools with 1029 children for 6 baseline days and 66 study days, yielding
      73,779 child days. The main outcomes were rates of handwashing and illness
      absenteeism. The intervention included an educational program and environmental
      changes. A simultaneous subtrial was run to test a home component. RESULTS: This
      multi-site intervention program produced sustained behavioral and environmental
      changes over a 6-month period. An approximately threefold increase in handwashing
      with soap was observed among preschool children exposed to the intervention.
      Neither the preschool nor the home intervention program reduced illness
      absenteeism or overall absenteeism. CONCLUSIONS: This trial illuminates the
      potential of the preschool as a promising venue for health promotion activities
      leading to sustained behavioral change, yet suggests the need for enhanced
      approaches for reducing illness absenteeism.

PMID- 16300824
TI  - Variability in perisylvian brain anatomy in healthy adults.
AB  - Gray matter volumes of Heschl's gyrus (HG), planum temporale (PT), pars
      triangularis (PTR), and pars opercularis were measured on MRI in 48 healthy right
      handers. There was the expected leftward PT asymmetry in 70.8%, and leftward PTR
      asymmetry in 64.6% of the sample. When asymmetry patterns within individuals were
      examined, there was not one typical pattern, rather several typical
      configurations were found. In addition, some combinations of asymmetry did not
      exist in our sample suggesting that some perisylvian anatomical configurations
      may provide a more suitable neural substrate for the development of language than
      others. There were also sex differences in HG. Men had rightward asymmetry and
      women demonstrated leftward asymmetry, due to women having smaller right HG,
      compared to men.

PMID- 16300826
TI  - Extension of a one-step self-etch adhesive into a multi-step adhesive.
AB  - One-step self-etch adhesives are undoubtedly the most user-friendly adhesives,
      but have been associated with lower bonding effectiveness as compared to two-step
      and three-step adhesives. Conversion of a one-step self-etch system into a two
      step self-etch adhesive by adding a bonding step, or into a three-step etch&rinse
      adhesive by adding a beforehand etching step and a bonding step might be tempting
      in order to improve bond strength. OBJECTIVES: The objective of this study was to
      investigate whether adding application steps influences the bond strength of a
      one-step self-etch adhesive. METHODS: In this study, the bonding effectiveness of
      two experimental one-step self-etch adhesives and three different commercial
      adhesives to enamel and dentin was determined using a micro-tensile bond-strength
      protocol. This procedure was repeated for the experimental adhesives transformed
      into two-step self-etch and three-step etch&rinse adhesives. In addition, their
      interaction with tooth tissue was investigated using TEM and Feg-SEM. RESULTS:
      Transforming a one-step into a two-step self-etch adhesive did improve the bond
      strength to enamel and dentin, though not significantly. By adding a preceding
      etching step, the bond strength to enamel was significantly improved, but that to
      dentin was decreased considerably. The latter must be attributed to hampered
      resin infiltration of the one-step self-etch adhesive within the relatively
      deeply exposed collagen fibril network. SIGNIFICANCE: Additional application of a
      hydrophobic bonding agent slightly improved bonding effectiveness. Adding a
      preceding etching step is beneficial for enamel but should be avoided for dentin
      as this will decrease bond strengths, and may even jeopardize the bonding
      durability.

PMID- 16300827
TI  - STAT3-mediated constitutive expression of SOCS3 in an undifferentiated rat
      trophoblast-like cell line.
AB  - In the trophoblast, constitutive expression of SOCS3 is important for the
      negative regulation of trophoblast giant cell differentiation. In this study, we
      analyzed the signaling pathway regulating the constitutive SOCS3 expression in
      undifferentiated Rcho-1 cells, which were derived from rat choriocarcinoma and
      consist of trophoblast stem cells that are capable of differentiating to
      trophoblast giant cells in vitro. PD98059, an MEK inhibitor, repressed the SOCS3
      expression but AG490, a JAK2 inhibitor, did not. Promoter deletion analysis
      revealed that the STAT response element (SRE) in the SOCS3 promoter is necessary
      for the promoter activity. Overexpression of STAT3 increased the SOCS3 promoter
      activity, whereas expression of dominant-negative STAT3 reduced it. Constitutive
      STAT3 tyrosine phosphorylation that was not inhibited by either AG490 or PD98059
      was demonstrated. Electrophoretic mobility shift assays showed the existence of a
      protein that bound to SRE and was supershifted with STAT3 antibody. This binding
      reaction was inhibited by neither AG490 nor PD98059. These findings imply that
      the ERK/MAPK pathway and STAT3 are involved in the constitutive activation of
      SOCS3 in undifferentiated Rcho-1 cells. Moreover, they indicate that the
      constitutive STAT3 tyrosine phosphorylation and the DNA binding activity of STAT3
      do not depend on the ERK/MAPK or JAK kinase pathway. These results suggest that a
      trophoblast-specific STAT3 activation pathway is important for the regulation of
      giant cell differentiation.

PMID- 16300828
TI  - L-carnitine is synthesized in the human fetal-placental unit: potential roles in
      placental and fetal metabolism.
AB  - Carnitine plays an indispensable role in fatty acid oxidation. Previous studies
      revealed that fetal carnitine is derived from the mother via transplacental
      transfer. Recent studies demonstrated the presence and importance of an active
      fatty acid oxidation system in the human placenta and in the human fetus. In view
      of these findings we decided to study carnitine metabolism in the fetal-placental
      unit by measuring carnitine metabolites, intermediary metabolites of carnitine
      biosynthesis, as well as the activity of carnitine biosynthesis enzymes in human
      term placenta, cord blood and selected embryonic and fetal tissues (5-20 weeks of
      development). Placenta contained low but detectable activity of gamma
      butyrobetaine dioxygenase. This enzyme, which was considered to be expressed only
      in kidney, liver and brain, catalyzes the last step in the carnitine biosynthesis
      pathway. In addition, our results show that human fetal kidney, liver and spinal
      cord already have the capacity to synthesize carnitine. The ability of the
      placenta and fetus to synthesize carnitine suggests that in circumstances when
      maternal carnitine supply is limited, carnitine biosynthesis by the fetal
      placental unit may supply sufficient carnitine for placental and fetal
      metabolism.

PMID- 16300829
TI  - Low dose hydroxylated PCB induces c-Jun expression in PC12 cells.
AB  - Polychlorinated biphenyls (PCBs) are known as environmental pollutants that may
      cause adverse health problems. Recently, accumulating evidence shows that PCBs
      express neurotoxicity through alteration of gene expression and signal
      transduction. On the other hand, c-Jun, a component of AP-1, is likely to
      coordinate transcription programs in response to various extracellular signals.
      However, little is known about the effects of PCBs on c-Jun expression. Here we
      investigated the expression of c-Jun in response to PCB. PC12 cells were
      incubated with hydroxylated PCB (4(OH)-2',3,3',4',5'-penta chlorobiphenyl, OH
      PCB) at a final concentration from 10(-8) to 10(-5)M. The level of c-Jun
      expression was increased by OH-PCB at relatively low-dose; concentration of OH
      PCB at 10(-8)M and 10(-7)M produced a 2.4- and 3.5-fold increase of c-Jun
      expression in respectively, compared with the values without OH-PCB treatment.
      Thyroid hormone (T3) did not induce such c-Jun expression, indicating that the
      effect of OH-PCB is not mediated through thyroid hormone signaling pathway. OH
      PCB also enhanced phosphorylation of c-Jun NH2-terminal kinases. To determine
      whether the activation of Ca2+ channel is involved in the OH-PCB-induced c-Jun
      expression, we examined it using a L-type voltage-gated Ca2+ channel blocker
      nimodipine. Nimodipine partially inhibited OH-PCB-induced c-Jun expression by
      50%. Moreover, Na+ channel antagonist tetrodotoxin inhibited OH-PCB-induced c-Jun
      expression completely. Taken together, our results indicate that exposure to OH
      PCB induces c-Jun expression, and the response may be triggered by depolarization
      of a plasma membrane via Na+ influx, followed by Ca2+ influx partially through
      voltage-gated Ca2+ channels.

PMID- 16300830
TI  - Human stem cells isolated from adult skeletal muscle differentiate into neural
      phenotypes.
AB  - Multipotent neural stem cells have been isolated from the adult [Kirschenbaum B,
      Nedergaard M, Preuss A, Barami K, Fraser RA, Goldman SA. In vitro neuronal
      production and differentiation by precursor cells derived from the adult human
      forebrain. Cereb Cortex 1994;4(6):576-89; Laywell ED, Kukekov VG, Steindler DA.
      Multipotent neurospheres can be derived from forebrain subependymal zone and
      spinal cord of adult mice after protracted postmortem intervals. Exp Neurol
      1999;156:430-3; Pluchino S, Quattrini A, Brambilla E, Gritti A, Salani G, Dina G,
      et al. Injection of adult neurospheres induces recovery in a chronic model of
      multiple sclerosis. Nature 2003;422:688-94] and embryonic [Vescovi AL, Parati EA,
      Gritti A, Poulin P, Ferrario M, Wanke E, et al. Isolation and cloning of
      multipotential stem cells from the embryonic human CNS and establishment of
      transplantable human neural stem cell lines by epigenetic stimulation. Exp Neurol
      1999;156:71-83] central nervous system (CNS). In addition, neural cells can be
      obtained from sources other than the CNS by differentiating stem cells from a non
      neural source down a neural lineage. This has previously been performed with
      pluripotent embryonic stem cells and adult stem cells derived from rat bone
      marrow [Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone
      marrow stromal cells differentiate into neurons. J Neurosci Res 2000;61:364-70;
      Woodbury D, Reynolds K, Black IB. Adult bone marrow stromal stem cells express
      germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis. J
      Neurosci 2002;69(6):908-17] and skeletal muscle [Romero-Ramos M, Vourc'h P, Young
      HE, Lucas PA, Wu Y, Chivatakarn O, et al. Neuronal differentiation of stem cells
      isolated from adult muscle. J Neurosci Res 2002;69:894-907]. Previously, we have
      isolated adult stem cells from human skeletal muscle with the potential to
      differentiate into mesoderm, ectoderm, and endoderm. The following in vitro
      experiments were designed to determine whether human adult stem cells behaved
      similarly to rat adult stem cells when both were isolated from skeletal muscle by
      the same procedure [Romero-Ramos M, Vourc'h P, Young HE, Lucas PA, Wu Y,
      Chivatakarn O, et al. Neuronal differentiation of stem cells isolated from adult
      muscle. J Neurosci Res 2002;69:894-907] and subjected to the same protocols to
      induce neurogenesis. The neural phenotypes that were created through the
      neurococktail or neurosphere protocol were analyzed for neural characteristics
      through morphology and immunohistochemistry antibody labeling for proteins to
      neurons (RT-97, beta-tubulin III, NF-160, NF-200, and synapsin), oligodendrocytes
      (CNPase and RIP), and astrocytes (GFAP). A calcium uptake assay also showed
      response to the neuronal excitotoxic agent glutamic acid. In conclusion, the
      neural differentiated stem cells derived from adult skeletal muscle may be a less
      invasive alternative for the treatment of CNS disorders over CNS derived neural
      stem cells.

PMID- 16300831
TI  - Mast cells modulate maintained neuronal activity in the thalamus in vivo.
AB  - Single cell unit activity of 187 neurons of 24 rats were analysed to study the
      possible involvement of intracranial mast cells on modifying thalamic neuronal
      activity. Mast cells were activated with microiontophoretical application of
      compound 48/80. This substance did not modify the firing rate of cortical or
      hippocampal neurons (no mast cells are found here), however it caused excitation
      (70% in females, 11% in males), or inhibition (7% in females, 33% in males) on
      thalamic neurons, possibly due to mast cell activation. In consecutive anatomical
      evaluation many partially or fully degranulated mast cells were found in the
      recorded thalamic areas.

PMID- 16300832
TI  - Human class-I restricted T cell associated molecule is highly expressed in the
      cerebellum and is a marker for activated NKT and CD8+ T lymphocytes.
AB  - We have previously reported the characterization of a novel immunoglobulin
      supergene family member, designated class-I MHC-restricted T cell associated
      molecule (CRTAM). Here we further characterize human CRTAM and find that it is
      highly expressed in the cerebellum, notably in Purkinje neurons. We identify
      CRTAM as a new member of the nectin-like (Necls) family and find significant
      expression of Necl-2 (IGSF4), a protein known to bind CRTAM and another member of
      the nectin superfamily, in the cerebellum. These findings suggest that CRTAM/Necl
      2 binding may contribute to neuronal interactions. We also show that, in the
      immune system, CRTAM expression is restricted to activated class-I MHC-restricted
      T cells, including NKT and CD8 T cells. CRTAM represents one of the most highly
      expressed surface markers of activated human CD8 T cells and NKT cells,
      suggesting it may have diagnostic uses in various human viral and autoimmune
      diseases.

PMID- 16300833
TI  - Infrared fluorescent immunofocus assay (IR-FIFA) for the quantitation of non
      cytopathic and minimally cytopathic viruses.
AB  - A novel method was developed for the precise quantitation of viruses using
      infrared fluorescent detection of foci of infection in conventional cell culture
      plates. In this assay, termed the infrared fluorescent immunofocus assay (IR
      FIFA), appropriate cell cultures were infected with serial dilutions of hepatitis
      A virus (HAV) or measles virus (MV) and maintained with a semi-solid overlay for
      1-5 days. Cell monolayers were fixed with formaldehyde, and then stained in
      succession with a primary monoclonal antibody and an Alexa Fluor 680 conjugate.
      Foci of infection (analogous to plaques) were detected by scanning culture plates
      using the Odyssey infrared imaging system and counted to determine the virus
      titre, expressed as focus forming units (FFU) per mL, as is done for conventional
      plaque assays. HAV and MV were used as models of minimally cytopathic viruses,
      and showed a linear dose-response between focus formation and virus dilution.
      Viral titres calculated using this method were comparable to conventionally used
      methods. The IR-FIFA was also successfully adapted to quantify duck hepatitis B
      virus (DHBV) as a model for a non-cytopathic virus. This simple and sensitive
      assay will have wide use for the quantitation of non-cytopathic and minimally
      cytopathic viruses.

PMID- 16300834
TI  - Development of a quantitative Light Cycler real-time RT-PCR for detection of
      avian reovirus.
AB  - A robust, ultrasensitive, and accurate quantitative assay was developed for avian
      reovirus (ARV) with the Light Cycler SYBR Green-based real-time reverse
      transcription-PCR (real-time LC RT-PCR). The assay exhibited high specificity as
      all negative controls and other avian pathogens, such as Newcastle disease virus
      (NDV), infectious bronchitis virus (IBV), infectious bursal disease virus (IBDV),
      avian influenza virus (AIV), and mycoplasma synovia (MS), failed to show any
      positive detection. A minimum of 39 copies/microl of ARV genomic RNA could be
      detected by the assay. By dilution analysis, the real-time LC RT-PCR developed in
      this study was 3-log more sensitive than the conventional RT-PCR for the
      detection of ARV. The vaccine and field isolates of ARV were detected by the real
      time LC RT-PCR. As a result of the high sensitivity and specificity of the assay
      with a relatively rapid and simple procedure, the real-time LC RT-PCR will be
      useful as a routine assay for the clinical diagnosis of ARV infection.

PMID- 16300835
TI  - Multiplex real-time PCR assay for simultaneous quantitation of human
      cytomegalovirus and herpesvirus-6 in polymorphonuclear and mononuclear cells of
      transplant recipients.
AB  - Human cytomegalovirus (HCMV) and human herpesvirus-6 (HHV-6) are two closely
      related viruses, which belong to the Herpesviridae family. Following primary
      infection, they are thought to persist for life as latent forms in mononuclear
      cells. HCMV and HHV-6 can cause considerable morbidity in immunocompromised
      individuals, such as transplant patients. A sensitive and specific LightCycler
      multiplex real-time PCR assay based on fluorescence energy transfer (known as
      FRET) was developed. This assay, by using two sets of hybridization probes
      specific for HHV-6 (A and B) and HCMV, can differentiate reliably and quantify
      simultaneously both viruses in order to diagnose reactivation processes. The
      assay was optimized and the lower limit of detection for both viruses was
      determined to be 10 viral genome copies per reaction. Both viruses were
      quantified in 83 peripheral blood mononuclear cells (PBMCs) and 87
      polymorphonuclear leukocytes (PMNLs) collected from 32 transplant recipients.
      This multiplex real-time quantitative PCR was finally compared with two other
      quantitation and detection assays used daily in laboratory (PCR DIG detection and
      antigenemia for HCMV, TaqMan Assay for HHV-6). This technique can be useful for
      the differentiation and quantitation of HCMV and HHV-6 for monitoring transplant
      patients.

PMID- 16300836
TI  - Development of a real-time PCR assay using SYBR Green chemistry for monitoring
      Marek's disease virus genome load in feather tips.
AB  - Feather follicles of birds infected with Marek's disease virus (MDV) serve as the
      sole source of infectious virus particles. The present study was aimed at
      developing a SYBR Green real-time PCR assay to detect and quantify MDV loads in
      feather tips targeting meq gene of the virus. The assay had a dynamic range of 8
      logs, mean inter- and intra-assay coefficient variation (CV) of <5% and minimum
      detection limit of 15 MDV genome copies when plasmid DNA was used as the
      template. The sensitivity of the assay was compared with that of the conventional
      PCR technique and found to be 2.5-10 times more sensitive than the conventional
      PCR technique. The assay was validated using feather tip DNA preparations derived
      from chickens infected with 250 plaque forming units (PFU) of RB1B strain of MDV
      and sampled on days 7, 14, 21 and 28 post-infection (p.i.) along with uninfected
      chickens. MDV genome was quantifiable in feather tips of infected birds by day 7
      p.i. and the number of MDV copies peaked by day 14 p.i., but then gradually
      decreased by day 28. This reliable real-time PCR assay may be used for monitoring
      MDV genome loads in tissues of experimentally or naturally infected birds.

PMID- 16300837
TI  - A real-time RT-PCR assay for the quantitative determination of adenoviral gene
      expression in tumor cells.
AB  - Oncolytic adenoviruses are exploited as possible anticancer agents in clinical
      trails. To monitor adenoviral gene expression, a real-time RT-PCR method with a
      LightCycler was developed that allows the rapid and easy quantification of a
      number of early and late adenoviral genes in infected tumor cells. Primers were
      designed that can amplify the spliced forms of the genes encoding E1A13S, DNA
      polymerase (Pol), pre-terminal protein (pTP), adenoviral death protein (ADP),
      Hexon (Hex) and Penton (Pent) genes. Standard curves were generated using two
      fold serial dilutions of cDNAs derived from non-small cell lung cancer (NSCLC)
      H460 cells infected for 24h with wild-type adenovirus serotype 5. For all genes
      correlation coefficients of the standard curves of 0.984 or higher were obtained.
      The dynamic range of the assay was sufficient to allow the quantitative
      determination of adenoviral gene expression during a lytic cycle. This RT-PCR
      assay could be used as a research tool to study the effect of host-cell factors
      or exogenous treatments on adenoviral gene expression. As example, it is shown
      that the procedure is suitable to detect changes in adenoviral gene expression in
      infected H460 cells treated with paclitaxel that is known to enhance the
      antitumor effect of oncolytic adenoviruses.

PMID- 16300838
TI  - Use of an internal control in a quantitative RT-PCR assay for quantitation of
      porcine epidemic diarrhea virus shedding in pigs.
AB  - Porcine epidemic diarrhea virus (PEDV), a member of the family Coronaviridae, has
      caused a devastating enteric disease in the Korean swine industry. Previously,
      the differences between virulent field PEDV strains and a Vero cell culture
      adapted PEDV DR13 strain were determined using restriction fragment length
      polymorphism analysis (RFLP), and PEDV shedding patterns in pigs were reported.
      In an extension to these studies, an internal control was constructed and
      quantitative analysis of virus shedding after oral inoculation was established. A
      parent field PEDV and a cell culture adapted PEDV DR13 were inoculated orally to
      colostrum-deprived 1-day-old piglets, commercial 2-week-old pigs, and sows (1-5
      ml dose, 10(5.8)-10(6.0) TCID(50)/0.1 ml). PEDV shedding was monitored every day
      and virus levels were measured using a quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) method. In fecal samples from experimentally
      inoculated pigs, the level of virus excreted peaked at 2 days after oral
      inoculation and gradually decreased thereafter. In addition, PEDV from field
      specimens was quantified using the same RT-PCR assay to determine shedding viral
      load. This suggests that measurement of PEDV shedding viral load in pigs, by
      quantitative RT-PCR, may be a useful tool for estimating the transmission
      potential of PEDV in the swine population.

PMID- 16300839
TI  - Atrazine concentrations, gonadal gross morphology and histology in ranid frogs
      collected in Michigan agricultural areas.
AB  - The triazine herbicide atrazine has been suggested to be a potential disruptor of
      normal sexual development in male frogs. The goals of this study were to collect
      native ranid frogs from sites in agricultural and non-agricultural areas and
      determine whether hypothesised atrazine effects on the gonads could be observed
      at the gross morphological and histological levels. Juvenile and adult green
      frogs (Rana clamitans), bullfrogs (R. catesbeiana) and leopard frogs (R. pipiens)
      were collected in the summers of 2002 and 2003. Atrazine concentrations were
      below the limit of quantification at non-agricultural sites, and concentrations
      did not exceed 2 microg/L at most agricultural sites. One concentration greater
      than 200 microg atrazine/L was measured once at one site in 2002. Hermaphroditic
      individuals with both male and female gonad tissue in either one or both gonads,
      were found at a low incidence at both non-agricultural and agricultural sites,
      and in both adults and juveniles. Testicular oocytes (TO) were found in male
      frogs at most of the sites, with the greatest incidence occurring in juvenile
      leopard frogs. TO incidence was not significantly different between agricultural
      and non-agricultural sites with the exception of juveniles collected in 2003.
      Atrazine concentrations were not significantly correlated with the incidence of
      hermaphroditism, but maximum atrazine concentrations were correlated with TO
      incidence in juvenile frogs in 2003. However, given the lack of a consistent
      relationship between atrazine concentrations and TO incidence, it is more likely
      the TOs observed in this study result from natural processes in development
      rather than atrazine exposure.

PMID- 16300840
TI  - The 5S ribosomal RNA gene from the early diverging protozoa Trichomonas
      vaginalis.

PMID- 16300841
TI  - Characterization of protein geranylgeranyltransferase I from the enteric protist
      Entamoeba histolytica.
AB  - Entamoeba histolytica is a unique protozoan parasite possessing both protein
      farnesyltransferase and geranylgeranyltrasferase I (GGT-I) for isoprenylation of
      small GTPases. In this study, we demonstrated unique enzymological properties of
      the amebic GGT-I (EhGGT-I), including substrate specificity and insensitivity to
      known mammalian inhibitors. Some of important residues of the catalytic beta
      subunit implicated in the specificity for GTPase acceptors and prenyl donors are
      substituted in EhGGT-I. Recombinant alpha and beta subunits of EhGGT-I, co
      expressed in Escherichia coli, showed activity to transfer geranylgeranyl to both
      human wild-type (CVLS) and mutant (CVLL) H-Ras, while the mammalian GGT-I
      geranylgeranylated, but not farnesylated, only mutant H-Ras. All the
      representative amebic Ras and Rho/Rac small GTPases with phenylalanine, leucine,
      methionine, or alanine terminus were preferentially geranylgeranylated by EhGGT
      I. This indicates that the acceptor specificity of the amebic GGT-I is remarkably
      broader than that of its mammalian counterpart. In contrast to EhFT, which
      farnesylates but not geranylgeranlylates solely EhRas4-CVVA, EhGGT-I also showed
      significant farnesyltransferase activity against Ras GTPase acceptors. EhGGT-I
      showed remarkable resistance to peptidomimetics known to inhibit mammalian GGT-I.
      Together with our previous observation that this parasite does not appear to
      depend on farnesylation for a majority of Ras and Rho/Rac, these data indicate
      that biological and biochemical advantages leading to the evolutional selection
      of this isoprenyl modification must exist uniquely in this parasitic protist.
      Finally, remarkable biochemical differences in binding to substrates and
      inhibitors between amebic and mammalian GGT-I highlight this enzyme as an
      attractive target for the development of new chemotherapeutics against amebiasis.

PMID- 16300842
TI  - Potentials and pitfalls of DNA array analysis of the endothelial stress response.
AB  - Endothelial cells respond to inflammatory stimuli with complex genetic
      alterations that determine the immune response and the outcome of the
      inflammatory process. An additional layer of complexity is added by the different
      phenotypes and functional heterogeneity of endothelial cells in the various
      tissues. To understand these complex gene response patterns and the regulatory
      pathways involved, many investigators increasingly use DNA microarray analysis.
      There are, however, many potential pitfalls in the use of microarrays that can
      result in false data and erroneous conclusions. This review surveys the
      principles of DNA microarray technology and its applications in endothelial cell
      research. We also attempt to outline some of the caveats and standard criteria
      that have to be considered in order to realize the full potential of microarrays
      in inflammation research.

PMID- 16300843
TI  - Endovascular stent for the aortic coarctation in a 1.7-kg premie presenting
      intractable heart failure.

PMID- 16300844
TI  - Chronic bifascicular block with intermittent complete atrioventricular block
      induced by hyperthyroidism.

PMID- 16300845
TI  - Beta-blocker therapy can mask ECG signs of pericarditis.
AB  - PR-segment changes of ECG can help differentiate acute myocardial infarct from
      pericarditis preventing the patient from an unnecessary coronarography. Here we
      present a case where beta-blocker therapy masked PR-segment changes.

PMID- 16300846
TI  - Radiation therapy: intensity modulated, image guided, biologically optimized and
      evidence based.

PMID- 16300847
TI  - Limb sparing approach: adjuvant radiation therapy in adults with intermediate or
      high-grade limb soft tissue sarcoma.
AB  - BACKGROUND: Limb soft tissue sarcomas (STS) are currently treated with limb
      sparing surgery (LSS) followed by radiation therapy (RT). PATIENTS AND METHODS:
      Between October 1994 and October 2002, 133 adult patients with intermediate or
      high-grade limb STS were approached by LSS+RT. RESULTS: RT related toxicity was
      manageable, with a low rate of severe effects. At 4-year median follow-up, there
      were 48 recurrences of any type, 23 of isolated local failure, and 35 of systemic
      spread w/o local failure. DFS and OS were influenced by disease stage II vs I,
      primary site in the upper limb vs lower limb, MPNST vs other types, induction
      therapy vs no induction, adequate resection vs marginal resection or involved
      margins, and good response to induction therapy vs bad response. DFS and OS were
      Patient's age and sex, tumor depth, acute or late toxicity of RT, or the interval
      of time between the date of definitive surgery and the start of RT did not affect
      DFS and or OS. CONCLUSIONS: The RT protocol is applicable in the era of
      complicated, expensive and time-consuming 3D therapy. Our results of LSS+RT in
      adults with limb HG STS are satisfactory.

PMID- 16300848
TI  - Role of radiotherapy in anaplastic ependymoma in children under age of 3 years:
      results of the prospective German brain tumor trials HIT-SKK 87 and 92.
AB  - BACKGROUND AND PURPOSE: To evaluate the outcome of very young children with
      anaplastic ependymoma after delayed or omitted radiotherapy (RT). MATERIALS AND
      METHODS: Children under age of 3 years with anaplastic ependymoma were enrolled
      in the HIT-SKK 87 trial from 1987. After surgery, low-risk patients (R0, M0)
      received maintenance chemotherapy until elective RT at age of three. In high-risk
      patients (R+, M+) intensive induction chemotherapy was followed by maintenance
      chemotherapy and subsequently delayed RT. If there was, progression radiotherapy
      started immediately. In the HIT-SKK 92, trial MTX-based chemotherapy was applied.
      RT was administered in non-responders only. RESULTS: Thirty-four children with
      anaplastic ependymoma were eligible (age 1.0-33.0 months). All children received
      chemotherapy. In 13 children, no RT was administered. Preventive RT after
      chemotherapy was given in nine, and salvage RT in 12 children. OS and PFS rates
      after 3-year were 55.9 and 27.3%, respectively. Twenty-five children relapsed.
      Positive impact on survival was observed in children with higher age, M0-stage,
      complete resection, and treatment with radiotherapy. Without RT only 3/13,
      children survived. CONCLUSION: Delaying RT jeopardizes survival even after
      intensive chemotherapy. Predominant site of failure is the primary tumor site. RT
      of the neuraxis should be omitted in localized disease.

PMID- 16300849
TI  - Effect of maternal deprivation on milk intake in normal and bilaterally facial
      nerve-injured developing rats.
AB  - We examined effect of maternal deprivation (2, 4 and 6h) on milk intake in
      developing rats. Milk intake was obtained by body weight gain after 1h lactation.
      The amounts of milk intake significantly differed depending on the duration of
      the deprived periods at P7 and P14 with proportional increase by longer
      deprivation. Further, milk intake was measured in the bilaterally facial nerve
      injured neonatal rats. The results show that milk intake is increased during
      development affected by maternal deprivation, and that milk intake of the facial
      nerve-injured group is decreased by 35% (2h), 7% (4h) and 7% (6h) at P7, and 25%
      (2h), 20% (4h) and 27% (6h) at P14 compared to that of the control group.

PMID- 16300850
TI  - Antimicrobial resistance of Escherichia coli O157 from cattle in Korea.
AB  - Of 45 Escherichia coli O157 isolates from cattle feces, which were collected
      between May 2000 and September 2003 in Korea, 32 were resistant to at least 1
      antibiotic and 28 were resistant to 4 or more antibiotics, with 32, 30 and 30 of
      the isolates being resistant to streptomycin, tetracycline and sulfisoxazole,
      respectively. Two isolates were resistant to fluoroquinolones and to 10 or more
      of the 22 other antimicrobial agents that were tested. Thirteen antimicrobial
      resistant patterns were observed. The most frequent resistance type, which was
      found for 11 isolates, was streptomycin-tetracycline-kanamycin-ampicillin
      piperacillin-cephalothin-sulfisoxazole-ticarcillin. Polymerase chain reaction
      (PCR) analysis of the isolates for E. coli O157 virulence markers revealed that
      25 of the resistant E. coli O157 isolates tested positive for stx2 or both stx1
      and stx2 genes. These findings suggest that many of the resistant E. coli O157
      isolates might cause disease in humans.

PMID- 16300851
TI  - Influence of the poly(lactide-co-glycolide) type on the leuprolide release from
      in situ forming microparticle systems.
AB  - The objective was to investigate the influence of poly(lactide-co-glycolide)
      (PLGA) type (molecular weight and end-group functionality) on the leuprolide
      release from in situ forming microparticle (ISM) systems. ISM systems are based
      on an emulsion of the PLGA solution dispersed in an oil phase. The polymer
      droplets solidify after contact with aqueous fluids and form microparticles in
      situ. In contrast to microparticles prepared by the classical solvent evaporation
      method, the use of the lower molecular weight PLGA resulted in ISM with a lower
      initial release than ISM prepared with the higher molecular weight PLGA. ISM
      prepared with PLGA combinations showed a decreasing initial release with
      increasing low-molecular-weight PLGA content. A slower solvent diffusion from the
      low-molecular-weight PLGA solution droplets into the release medium led to a less
      porous structure of the resulting microparticles, thus explaining the lower
      initial release. PLGA with free carboxylic acid end groups led to a lower drug
      release compared to PLGA with esterified end groups. 6-month controlled release
      leuprolide ISM could be obtained by blending poly(lactides) (PLA) with different
      molecular weights.

PMID- 16300852
TI  - [Functional status, scholastic placement after rehabilitation and follow-up of
      children with traumatic brain injury: a retrospective study of 48 patients].
AB  - OBJECTIVE: To evaluate the follow-up of children with traumatic brain injury
      (TBI). POPULATION AND METHODS: A retrospective study during 4.5 years of 48
      children with TBI. We measured GOS during admission and after rehabilitation and
      where children were placed after hospitalisation. RESULTS: Most patients were
      males; the mean age was 9.4 years (range 14 months to 16.5 years). The
      rehabilitation length was 11.4 months. Most children (77%) had a good functional
      outcome. For 23%, placement was in establishments for severely handicapped
      people, for 35.4%, an environment with specific support, and for 37.5%, an
      environment without specific support. After 2 years, 43.7% of infants were lost
      to follow up. CONCLUSION: Rehabilitation and functional results have improved for
      children with TBI, but some improvements must be made.

PMID- 16300853
TI  - Quality of care from the patient's perspective in pediatric diabetes care.
AB  - This study aimed to investigate perceived quality of diabetes care. A geographic
      population of 400 type 1 diabetes patients <20 years received the validated
      questionnaire quality of care from the patient's perspective (QPP) including
      additional context-specific items. Primary endpoints were perceived reality of
      care by specific items and factors and their subjective importance, respectively.
      Relations to severe hypoglycemia, HbA1c, insulin dose, BMI, age, duration and
      sociodemographic factors were also studied. On average, a high perceived quality
      of care was reported from both parents and adolescents (response rate 285/400
      (71%) and 155/237 (65%), respectively); highest regarding possibility to talk to
      nurse/doctor in privacy, respect, general atmosphere, continuity in patient
      physician relationship and patient participation. Lower perceived reality with
      higher subjective importance was seen for information about results from medical
      examinations and treatments and information about self-care, access to care and
      waiting time. While parents' and their adolescents' mean ratings correlated well
      for reality r=0.95 (p<0.001) and importance r=0.53 (p=0.023), parents rated
      reality level higher (p=0.012) and importance even higher (p<0.001). The QPP
      instrument used with additional context-specific items can provide specific
      information to be used in quality of care development. In our setting,
      improvements are needed regarding patient information, access to care and waiting
      time.

PMID- 16300854
TI  - Lung cancer, a new challenge in the HIV-infected population.
AB  - HIV infection predisposes patients to AIDS-defining malignancies, some of which,
      such as Kaposi's sarcoma and non-Hodgkin lymphoma, can affect the lungs. In 1996,
      AIDS-related mortality started to fall sharply in industrialized countries
      following the introduction of highly active antiretroviral treatments (HAART).
      This was accompanied by an increase in the proportion of deaths attributable to
      non AIDS-defining solid tumors, and especially lung cancer (LC). The increased
      risk of LC relative to the general population of the same age seems to be due
      partly to a higher prevalence of smoking among HIV-infected subjects. The average
      age of HIV-infected patients at LC diagnosis is about 45 years. Most patients are
      symptomatic at diagnosis and have only mild or moderate immunosuppression. LC is
      diagnosed when it is locally advanced or metastatic (stages III-IV) in 75-90% of
      cases, as in patients with unknown HIV serostatus. Adenocarcinoma is the most
      frequent histologic type. The prognosis of LC is poorer in HIV-infected patients
      than in the general population. Data on the efficacy and toxicity of chemotherapy
      in this setting are rare and rather imprecise. Surgery remains the reference
      treatment for localized disease in patients with adequate functional status and
      general health, regardless of their immune status. Prospective clinical trials
      are needed to define the optimal LC treatment strategies in HIV-infected
      patients.

PMID- 16300855
TI  - Differential response of photosynthesis in greenhouse- and field-ecotypes of
      tomato to long-term chilling under low light.
AB  - Three greenhouse- and four field-ecotype varieties of domestic tomato
      (Lycopersicon esculentum) were compared for the sensitivity of their
      photosynthetic apparatus to chilling under low light intensity. After chilling at
      12/7 degrees C under 100 micromolm(-2)s(-1) of light for 10 days, they were
      allowed to recover at 25/18 degrees C and 600 micromolm(-2)s(-1) of light for 10
      days. For both pre-chilling and recovered plants, greenhouse-ecotype varieties
      did not necessarily show higher net CO(2) assimilation rate (A), quantum yield of
      electron transport at PSII (Phi(PSII)) and photochemical quenching (q(P)) than
      field-ecotype varieties. However for the post-chilling period, greenhouse-ecotype
      varieties, exhibited higher A, and Phi(PSII) values than field-ecotype varieties.
      The difference in Phi(PSII) was found to be largely due to q(P). The absence of
      ecotypic differences in pre-chilling plants indicates that the trait was not
      expressed constitutively, but relied mainly on adaptation/acclimation mechanisms.
      Greenhouse-ecotype varieties were able to adapt to low temperature and low light
      more quickly, and then exhibited higher A, Phi(PSII), q(P) values and greater re
      growth capacity after chilling than field-ecotype varieties. Plant re-growth
      capacity after chilling was highly correlated with Phi(PSII) and q(P) measured in
      chilled plants, suggesting the usefulness of Phi(PSII) and q(P) measured at low
      temperature after defined chilling stresses as screening indexes for chilling
      tolerance in breeding programs.

PMID- 16300856
TI  - Vascular determinants of cholinergic deficits in Alzheimer disease and vascular
      dementia.
AB  - Alzheimer's disease (AD) and vascular dementia (VaD) are widely accepted as the
      most common forms of dementia. Cerebrovascular lesions frequently coexist with
      AD, creating an overlap in the clinical and pathological features of VaD and AD.
      This review assembles evidence for a role for cholinergic mechanisms in the
      pathogenesis of VaD, as has been established for AD. We first consider the
      anatomy and vascularization of the basal forebrain cholinergic neuronal system,
      emphasizing its susceptibility to the effects of arterial hypertension, sustained
      hypoperfusion, and ischemic cerebrovascular disease. The impact of aging and
      consequences of disruption of the cholinergic system in cognition and in control
      of cerebral blood flow are further discussed. We also summarize preclinical and
      clinical evidence supporting cholinergic deficits and the use of cholinesterase
      inhibitors in patients with VaD. We postulate that vascular pathology likely
      plays a common role in initiating cholinergic neuronal abnormalities in VaD and
      AD.

PMID- 16300857
TI  - Design, synthesis and antiproliferative activity of some new azapyranoxanthenone
      aminoderivatives.
AB  - Some novel aminosubstituted azapyranoxanthenones, bearing structural similarity
      to the acridone alkaloid acronycine, have been designed and synthesized. Their in
      vitro cytotoxicities against the murine L1210 leukemia and the human solid tumor
      HT-29 cell lines have been investigated. Their eventual selective effect on a
      phase of the cell cycle was evaluated, using HT-29 cells. A number of the new
      derivatives exhibited interesting cytotoxic activity against the human solid
      tumor cell line.

PMID- 16300858
TI  - Cancer chemopreventive activity of sulforamate derivatives.
AB  - Chemoprevention can be defined as an intervention in the carcinogenic process by
      use of natural or synthetic substances. Induction of Phase II enzyme is an
      important mechanism of chemoprevention. In the present studies we have
      synthesized several derivatives of (+)(-) 4-methylsulfinyl-1-(S
      methyldithiocarbamyl)-butane (sulforamate) and evaluated their effectiveness as
      monofunctional inducer of the NAD(P)H Quinone oxidoreductase [quinone reductase
      (QR)] a phase II enzyme in cultured Hepa1c1c7 murine hepatoma cells. The
      cytotoxicity of some of the derivatives was strongly reduced in comparison to [(
      )-1-isothiocyanato-4(R)-(methylsulfinyl)butane] (sulforaphane). However, the
      induction potential of these compounds was comparable to sulforaphane. On the
      basis of these results sulforamate derivatives can be regarded as simple,
      inexpensive and readily available chemopreventive agents.

PMID- 16300859
TI  - Synthesis and leishmanicidal activities of 1-(4-X-phenyl)-N'-[(4-Y
      phenyl)methylene]-1H-pyrazole-4-carbohydrazides.
AB  - 1H-pyrazole-4-carbohydrazides were synthesized and their leishmanicidal in vitro
      activities and cytotoxic effects were investigated. The drugs prototypes of these
      new compounds (ketoconazole, benznidazole, allopurinol and pentamidine) were also
      tested. It was found that among all the 1H-pyrazole-4-carbohydrazides derivatives
      examined, the most active compounds were those with X = Br, Y = NO2 (27) and X =
      NO2, Y = Cl (15) derivatives which showed to be most effective on promastigotes
      forms of L. amazonensis than on L. chagasi and L. braziliensis species. When
      tested against murine peritoneal macrophages as mammalian host cell controls of
      toxicity, 1-(4-Br-phenyl)-N'-[(4-NO(2)-phenyl)methylene]-1H-pyrazole-4
      carbohydrazides (27) (EC50 = 50 microM l(-1)) and 1-(4-NO2-phenyl)-N'-[(4-Cl
      phenyl)methylene]-1H-pyrazole-4-carbohydrazides (15) EC50 = 80 microM l(-1))] was
      reasonably toxic. However, both compounds were less toxic than pentamidine and
      ketoconazole. These results provide new perspectives on the development of drugs
      with activities against Leishmania parasite.

PMID- 16300860
TI  - Synthesis and antiamoebic activity of new 1-N-substituted thiocarbamoyl-3,5
      diphenyl-2-pyrazoline derivatives and their Pd(II) complexes.
AB  - Some 1-N-substituted thiocarbamoyl-3,5-diphenyl-2-pyrazoline derivatives (L), 1-8
      were synthesized by a base-catalyzed Claisen-Schmidt condensation of benzaldehyde
      with acetophenone followed by cyclization with various N-4 substituted
      thiosemicarbazides. The palladium(II) complexes [PdLCl2], 1a-8a of these ligands
      were obtained by reacting them with [Pd(DMSO)2Cl2]. All compounds have been
      characterized by means of elemental analyses, electronic, IR, 1H NMR and mass
      spectroscopic data, while the complexes have additionally been characterized by
      thermogravimetric patterns. The in vitro antiamoebic activity was evaluated
      against the HM1:IMSS strain of Entamoeba histolytica and the results were
      compared with the standard drug, metronidazole. The preliminary test results
      showed that the complexes had better antiamoebic activity than their respective
      ligands. Moreover, the complexes showed better inhibition of the test organism.
      The results suggest that the ligands 4, 7 and the complexes 2a-4a, 6a-8a were
      found with IC50 lower than that of the standard drug metronidazole and thus are
      better inhibitor of growth of E. histolytica.

PMID- 16300861
TI  - [Use of anticoagulant treatments in the elderly].
AB  - PURPOSE: The frequency of pathologies requiring anticoagulant treatment
      (thromboembolic disease, atrial fibrillation) is particularly high in people
      above 75. The risk of haemorrhagic complications is also highest in this
      population of patients.Therefore, the assessment of the risk/benefit ratio of an
      anticoagulant treatment may overestimate the haemorrhagic risk and lead to the
      under-using of anticoagulant treatment in such pathologies as atrial
      fibrillation. CURRENT KNOWLEDGE AND KEY-POINTS: However, the use of "classical"
      anticoagulant treatments such as non-fractionated heparin, low-molecular-weight
      heparin, and above all, antivitamin K requires special precautions. Several
      hemorrhagic risk factors are well known and should be spotted out. Finally, the
      risk/benefit ratio of an anticoagulant treatment in the elderly patients must
      rely on a comprehensive geriatric assessment. PROSPECTS AND PROJECTS: In the era
      of "new anticoagulant treatments", and particularly of per-os antithrombin, it
      may seem anachronous to issue a statement over the use of "classical
      anticoagulant treatments", but in the present state of knowledge, the evaluation
      of these new molecules is not sufficient in the elderly population of patients.

PMID- 16300862
TI  - Using on-line video clips to enhance self-efficacy toward dealing with difficult
      situations among nursing students.
AB  - The aim of the study was twofold. The first aim was to develop on-line video clip
      material that showed examples of nurses dealing with potentially difficult and
      delicate patient groups. The second aim was to evaluate the effectiveness of
      video clip materials for enhancing nursing student's self-efficacy to effectively
      communicate with the type of patients described above. The production of
      contextually relevant video clip material involved the identification of relevant
      material based on real experiences, writing appropriate scripts, recruiting
      actors, recording the performances and producing them in a form that could be
      accessed on-line. Self-report questionnaires were used to assess the
      effectiveness of video clip material. Level 1 (n = 145) nursing students
      completed a self-efficacy measure that assessed confidence to deal with
      situations such as breaking news of death, working with children, people with
      disability and aggressive behaviour at the start and the end of the module.
      Results indicated that student's self-efficacy increased noticeably over the
      course of the module. Differences between increases in self-efficacy attributed
      to watching videos or attending lectures were marginal. Findings suggest that
      using video clips that show students effectively coping with adverse situations
      provide an effective teaching approach for enhancing self-efficacy. Future
      research is needed to test the extent to which self-efficacy measures relate with
      nursing performance.

PMID- 16300864
TI  - A preliminary evaluation of alternative adjuvants to alum using a range of
      established and new generation vaccine antigens.
AB  - Although alum is the most commonly used vaccine adjuvant, it has some limitations
      for use with the next generation recombinant antigens. We explored the use of
      alternative adjuvant formulations (poly lactide co-glycolide (PLG)
      microparticles, MF59 emulsion, CAP and l-tyrosine suspension) in comparison with
      five different vaccine antigens--namely, diphtheria toxoid (DT), tetanus toxoid
      (TT), HBsAg, Men C conjugate and MB1. The results indicated that although alum
      was optimal for bacterial toxoid based vaccines, it was not highly potent for
      MB1, Men C or HBsAg antigens. MF59 emulsion stood out as a good alternative to
      alum for TT, HBsAg, MB1 and Men C vaccines. On the other hand l-tyrosine
      suspension and CAP did not enhance immune responses over alum with most antigens.
      PLG microparticles were comparable or better than alum with both MB1 and Men C
      conjugate vaccine. The study indicates that it is possible to replace alum with
      other adjuvant formulations like MF59 and PLG and maintain and/or improve immune
      responses with some vaccine antigens.

PMID- 16300863
TI  - Protective efficacy of an oral vaccine to reduce carriage of Borrelia burgdorferi
      (strain N40) in mouse and tick reservoirs.
AB  - Lyme disease is caused by the spirochete Borrelia burgdorferi, which is
      transmitted through the bite of infected Ixodes ticks. Vaccination of mice with
      outer surface protein A (OspA) of B. burgdorferi has been shown to both protect
      mice against B. burgdorferi infection and reduce carriage of the organism in
      feeding ticks. Here we report the development of a murine-targeted OspA vaccine
      utilizing Vaccinia virus to interrupt transmission of disease in the reservoir
      hosts, thus reducing incidence of human disease. Oral vaccination of mice with a
      single dose of Vaccinia expressing OspA resulted in high antibody titers to OspA,
      100% protection of vaccinated mice from infection with B. burgdorferi, and
      significant clearance of B. burgdorferi from infected ticks fed on vaccinated
      animals. The results indicate the vaccine is effective and may provide a manner
      to reduce incidence of Lyme disease.

PMID- 16300865
TI  - Immunological adjuvant effect of Glycyrrhiza uralensis saponins on the immune
      responses to ovalbumin in mice.
AB  - In this study, the haemolytic activities of Glycyrrhiza uralensis saponins (GLS)
      and its adjuvant potentials on the cellular and humoral immune responses of ICR
      mice against ovalbumin (OVA) were evaluated. We determined the haemolytic
      activity of GLS using 0.5% rabbit red blood cell. Haemolytic percents of GLS
      treated red blood cell were 11.20 and 5.54% at the concentrations of 500 and 250
      microg/ml, respectively. ICR mice were immunized subcutaneously with OVA 100
      microg alone or with OVA 100 microg dissolved in saline containing Alum (200
      microg), QuilA (10 and 20 microg), or GLS (50, 100, or 200 microg) on Days 1 and
      15. Two weeks later (Day 28), concanavalin A (Con A)-, lipopolysaccharide (LPS)-,
      and OVA-stimulated splenocyte proliferation and OVA-specific serum antibodies
      were measured. GLS significantly enhanced the Con A-, LPS-, and OVA-induced
      splenocyte proliferation in the OVA-immunized mice at a dose of 100 microg
      (P<0.025). OVA-specific IgG, IgG1, and IgG2b antibody titers in serum were also
      significantly enhanced by GLS compared with OVA control group (P<0.025).
      Moreover, no significant differences (P>0.05) were observed between enhancing
      effect of GLS and QuilA on the OVA-specific IgG, IgG1, and IgG2b antibody
      responses to OVA in mice. The results suggest that GLS showed a slight haemolytic
      effect and enhanced significantly a specific antibody and cellular response
      against OVA in mice, and deserved further researches to be developed as
      immunological adjuvant.

PMID- 16300866
TI  - Cross-protective immunity in calves conferred by a DNA adenine methylase
      deficient Salmonellaenterica serovar Typhimurium vaccine.
AB  - The global trend towards intensive livestock production is associated with
      increased fecal oral pathogen transmission resulting in a high prevalence of
      Salmonella. Since many pathogenic Salmonella serovars are often endemic to
      livestock production systems, it is desirable to develop a vaccine that is
      capable of eliciting immunity to more than one serovar. Here we examined whether
      immunization with a modified live Salmonella enterica serovar Typhimurium vaccine
      strain lacking the DNA adenine methylase (Dam) conferred protection in calves
      against a heterologous S. enterica Dublin challenge. Vaccinated animals
      challenged with a virulent Dublin strain exhibited a significant attenuation of
      clinical disease (improved attitude scores and reduced fever and diarrhea) and a
      concomitant reduction in Dublin fecal shedding and colonization of mesenteric
      lymph nodes (MLN) compared to non-vaccinated control animals. These data suggest
      that vaccination with a dam(-) Typhimurium vaccine strain conferred significant
      cross-protection against clinical disease in cattle attributable to heterologous
      challenge with Dublin.

PMID- 16300867
TI  - Candidate peptide-vaccines induced immunity against CSFV and identified
      sequential neutralizing determinants in antigenic domain A of glycoprotein E2.
AB  - Antigenic domain A is a highly conserved unit on envelope protein E2 of classical
      swine fever virus (CSFV). It was found that mutant E2 containing only unit A,
      with the unit BC deleted, provided immunized pigs with complete protection
      against the lethal challenge. In this study, six overlapping peptides (A1-A6)
      covering this unit were synthesized and conjugated to bovine serum albumin (BSA).
      Two candidate multi-peptide-vaccines (MPVs) using aluminum adjuvant successfully
      induced potent immunity against CSFV in pigs. Although both candidate MPVs failed
      to provide complete protection, they showed better protective activity than that
      induced by C-strain. Subsequently, neutralizing epitopes in unit A were
      identified using a panel of peptide-vaccines (PVs). Six candidate peptide
      vaccines (PV-An, n=1-6) were separately given to six groups of pigs. Among these
      candidates, PV-A2 and PV-A6 exhibited the most potent protective activity, while
      the other four showed weaker or almost no effects. Moreover, the polyclonal
      antibodies induced by PV-A2 and PV-A6 were capable of neutralizing C-strain virus
      at the dilution 1:16 in vitro. Thus, two principal sequential neutralizing
      determinants covered by peptide A2 (aa792-814) and A6 (aa844-865) were
      demonstrated to exist in the antigenic domain A, and can be recruited in
      developing new effective "marker vaccine" against CSFV.

PMID- 16300868
TI  - Influence of clinical outcome and outcome period definitions on estimates of
      absolute clinical and economic benefits of influenza vaccination in community
      dwelling elderly persons.
AB  - Studies assessing the clinical and economic benefits of vaccination in the
      elderly have used different clinical outcomes (e.g. hospitalizations for
      pneumonia or influenza versus hospitalizations for respiratory and cardiovascular
      causes) and different outcome periods (e.g. peak versus total influenza season)
      on which to base estimates of clinical effectiveness and cost effectiveness. We
      explored the implications of these varying approaches by comparing two health
      economic analysis models of influenza vaccination of community-dwelling elderly
      persons. We developed computerized models using clinical data from 3 large US
      HMOs for the 1998-1999 and 1999-2000 influenza seasons. The primary health
      economic model used a broad definition of clinical events and outcome period and
      included hospitalizations for all respiratory and cardiovascular events that
      occurred during the entire influenza season. The alternative model used more
      restrictive definitions and included pneumonia or influenza hospitalizations
      occurring during the peak influenza season. The results of Monte Carlo simulation
      showed that, with the more inclusive primary model, influenza vaccination
      resulted in net medical care cost savings due to fewer respiratory or
      cardiovascular hospitalizations of Dollars 71/person vaccinated (5th-95th
      percentile Dollars 32-118) and net savings of Dollars 809/year of life saved (5th
      95th percentile Dollars 331-1450). In contrast, the alternate model found costs
      of Dollars 3.50/person vaccinated (5th-95th percentile Dollars -11 to 5) and net
      costs of Dollars 91/year of life saved (5th-95th percentile Dollars -309 to 126).
      Our findings confirm that influenza vaccination of the elderly is most likely
      cost saving and supports policies and programs that advocate routine immunization
      of all persons 65 and older. They also highlight how different outcome
      definitions can influence the results of health economic analyses.

PMID- 16300869
TI  - CpG oligodeoxynucleotides activate dendritic cells in vivo and induce a
      functional and protective vaccine immunity against a TERT derived modified
      cryptic MHC class I-restricted epitope.
AB  - The use of synthetic peptides derived from tumor-associated Ags is attractive for
      the development of antitumoral vaccines as far as strong adjuvants are found to
      render them immunogenic. Here, we investigated the possibility to enhance the CD8
      response against the human and mouse shared TERT(572Y) HLA-A*0201 restricted
      modified cryptic peptide by using ODN-CpG as adjuvant. Humanized transgenic mice
      were immunized with the TERT(572Y) modified cryptic peptide in the presence of
      ODN-CpG and compared to mice immunized in IFA. By contrast with IFA, we first
      showed that, in vivo, ODN-CpG leads to the recruitment of dendritic cells in the
      lymph nodes draining the injection site. Those cells and especially the CD11c+
      CD11b- CD8a+ lymphoid and the CD11c+ B220+ plasmacytoid dendritic cells were
      activated as shown by up-regulation of CD40 at their cell surface. Immunization
      against TERT(572Y) peptide in the presence of ODN-CpG rather than IFA led to a
      strong CD8 response and can delayed mortality in an induced tumor model. Study of
      the CD8 response obtained after antigenic challenge suggested that a functional
      memory response is induced upon vaccination with ODN-CpG. Thus, MHC class I
      restricted epitope in combination of ODN-CpG is a promising and rather simple
      cancer vaccine formulation.

PMID- 16300870
TI  - The wealthy get healthy, the poor get poorly? Lay perceptions of health
      inequalities.
AB  - Research repeatedly identifies an association between health and socio-economic
      status-richer people are healthier than poorer people. Richard Wilkinson has
      posited that socio-psychological mechanisms may be part of the explanation for
      the fact that socio-economic inequalities run right across the social spectrum in
      wealthy societies. He argues that polarised income distributions within countries
      have a negative impact on stress, self-esteem and social relations which, in
      turn, impact on physical well-being. How people experience and perceive
      inequalities is central to his thesis. However, relatively little empirical work
      has explored such lay perceptions. We attempt to address this gap by exploring
      how people see inequality, how they theorise its impact on health, and the extent
      to which they make personal and social comparisons, by drawing on 14 focus group
      discussions in Scotland and the north of England. Contrary to other research
      which suggests that people from more deprived backgrounds are more reluctant to
      acknowledge the effects of socio-economic deprivation, our findings demonstrate
      that, in some contexts at least, people from less favourable circumstances
      converse in a way to suggest that inequalities deeply affect their health and
      well-being. We discuss these findings in the light of the methodological
      challenges presented for pursuing such research.

PMID- 16300871
TI  - Men's involvement in the South African family: engendering change in the AIDS
      era.
AB  - The literature on the South African family and its response to the HIV/AIDS
      epidemic is rife with accounts of men that reflect a deficit model of male
      involvement. Few acknowledge the historical, economic and social complexities of
      male involvement in family life. As the South African family undergoes
      demographic, social and economic transformation there is a need to describe the
      range of roles played by all household members, including men. This paper
      examines data collected over two and a half years from a small sample of
      households affected by HIV/AIDS in rural KwaZulu Natal, South Africa. Non
      participant observations were made during outreach visits by research staff to
      twenty households caring for at least one adult with disease symptoms indicative
      of TB or AIDS. We find that men are positively involved with their families and
      households in a wide range of ways. They care for patients and children,
      financially support immediate and extended family members and are present at
      home, thereby enabling women to work or support other households. As the
      qualitative data demonstrate, however, such activities are often not
      acknowledged. The dominant perception of both female respondents and research
      assistants continues to be that men are not caring for their families because
      they are irresponsible and profligate. We consider reasons why this disjuncture
      exists and how more men might be encouraged to fulfil such roles and activities
      as their families and households suffer the social and economic impacts of
      HIV/AIDS.

PMID- 16300872
TI  - Perospirone in the treatment of schizophrenia: effect on verbal memory
      organization.
AB  - The present study was performed to determine if perospirone, a novel
      antipsychotic drug with D2/5-HT2A antagonist and partial 5-HT1A agonist
      properties, would improve memory organization in twelve patients with chronic
      schizophrenia. Switching to equivalent dose of perospirone from prior
      antipsychotic medication was associated with a significant improvement in indices
      of verbal memory organization of the Auditory Verbal Learning Test. Negative
      symptoms and extrapyramidal side effects were also ameliorated after switching to
      perospirone. The distinct cognitive enhancement profile of perospirone may be
      attributable to its partial 5-HT1A agonist action.

PMID- 16300873
TI  - Binding analyses for the interaction between plant virus genome-linked protein
      (VPg) and plant translational initiation factors.
AB  - The turnip mosaic virus (TuMV) genome-linked protein (VPg) and Arabidopsis
      thaliana translation initiation factors were expressed and purified in order to
      investigate their binding properties and kinetics. Affinity chromatography on
      m(7)GTP-sepharose showed that bound A. thaliana eIF(iso)4E was eluted with crude
      TuMV VPg. Further column studies with purified VPg and other A. thaliana eIF4E
      isoforms showed that VPg preferentially bound eIF(iso)4E. Structural data
      implicate Trp-46 and Trp-92 in eIF(iso)4E in cap recognition. When Trp-46 or Trp
      92 were changed to Leu, eIF(iso)4E lost the ability to form a complex with both
      VPg and m(7)GTP-sepharose. This suggests that the VPg-binding site is located in
      or near the cap-recognition pocket on eIF(iso)4E. Affinity constants for the
      interactions with eIF(iso)4E of VPg and capped RNA oligomer were determined using
      surface plasmon resonance (SPR). The K(D) values showed that the binging affinity
      of VPg for eIF(iso)4E is stronger than that of capped RNA. This suggests that
      viral VPg can interfere with formation of a translational initiation complex on
      host plant cellular mRNA by sequestering eIF(iso)4E. Further experiments with
      affinity chromatography showed that VPg forms a ternary complex with eIF(iso)4E
      and eIF(iso)4G. Thus, VPg may participate in viral translational initiation by
      functioning as an alternative cap-like structure.

PMID- 16300874
TI  - The restless legs syndrome.
AB  - The restless legs syndrome (RLS) is one of the commonest neurological
      sensorimotor disorders at least in the Western countries and is often associated
      with periodic limb movements (PLM) during sleep leading to severe insomnia.
      However, it remains largely underdiagnosed and its underlying pathogenesis is
      presently unknown. Women are more affected than men and early-onset disease is
      associated with familial cases. A genetic origin has been suggested but the mode
      of inheritance is unknown. Secondary causes of RLS may share a common underlying
      pathophysiology implicating iron deficiency or misuse. The excellent response to
      dopaminegic drugs points to a central role of dopamine in the pathophysiology of
      RLS. Iron may also represent a primary factor in the development of RLS, as
      suggested by recent pathological and brain imaging studies. However, the way
      dopamine and iron, and probably other compounds, interact to generate the
      circadian pattern in the occurrence of RLS and PLM symptoms remains unknown. The
      same is also the case for the level of interaction of the two compounds within
      the central nervous system (CNS). Recent electrophysiological and animals studies
      suggest that complex spinal mechanisms are involved in the generation of RLS and
      PLM symptomatology. Dopamine modulation of spinal reflexes through dopamine D3
      receptors was recently highlighted in animal models. The present review suggests
      that RLS is a complex disorder that may result from a complex dysfunction of
      interacting neuronal networks at one or several levels of the CNS and involving
      numerous neurotransmitter systems.

PMID- 16300875
TI  - Negative second virial coefficients as predictors of protein crystal growth:
      evidence from sedimentation equilibrium studies that refutes the designation of
      those light scattering parameters as osmotic virial coefficients.
AB  - The effects of ammonium sulphate concentration on the osmotic second virial
      coefficient (BAA/MA) for equine serum albumin (pH 5.6, 20 degrees C) have been
      examined by sedimentation equilibrium. After an initial steep decrease with
      increasing ammonium sulphate concentration, BAA/MA assumes an essentially
      concentration-independent magnitude of 8-9 ml/g. Such behaviour conforms with the
      statistical-mechanical prediction that a sufficient increase in ionic strength
      should effectively eliminate the contributions of charge interactions to BAA/MA
      but have no effect on the covolume contribution (8.4 ml/g for serum albumin). A
      similar situation is shown to apply to published sedimentation equilibrium data
      for lysozyme (pH 4.5). Although termed osmotic second virial coefficients and
      designated as such (B22), the negative values obtained in published light
      scattering studies of both systems have been described incorrectly because of the
      concomitant inclusion of the protein-salt contribution to thermodynamic
      nonideality of the protein. Those negative values are still valid predictors of
      conditions conducive to crystal growth inasmuch as they do reflect situations in
      which there is net attraction between protein molecules. However, the source of
      attraction responsible for the negative virial coefficient stems from the protein
      salt rather than the protein-protein contribution, which is necessarily positive.

PMID- 16300876
TI  - Cardiovascular risk factors in patients aged 85 or older with ischemic stroke.
AB  - OBJECTIVES: To define a cardiovascular risk factor profile in very old patients
      with ischemic stroke. PATIENTS AND METHODS: Data from a prospective hospital
      based stroke registry was collected. Demographic characteristics and
      cardiovascular risk factors in individuals aged 85 years or older with ischemic
      stroke (n=303) were compared with patients under 85 years (n=1537). RESULTS: The
      study population accounted for 16.5% of all cases of ischemic stroke. The mean
      (S.D.) age was 88.2 (2.8) years (70% women). Hypertension occurred in 44.9% of
      patients, atrial fibrillation in 42.6%, diabetes in 16.2%, and congestive heart
      failure in 15.5%. The most frequent stroke subtypes were cardioembolic (36%) and
      atherothrombotic (31.4%) infarction. Congestive heart failure (odds ratio
      [OR]=3.62), chronic renal disease (OR=2.54), female sex (OR=2.27), previous
      cerebrovascular disease (OR=1.71), and atrial fibrillation (OR=1.38) were
      significantly associated with ischemic stroke, whereas diabetes (OR=0.68),
      hypertension (OR=0.61), hyperlipidemia (OR=0.45), and heavy smoking (OR=0.21)
      occurred more frequently in patients under 85 years. CONCLUSION: Adequate
      treatment of potentially modifiable risk factors, including congestive heart
      failure, chronic renal disease, and atrial fibrillation may contribute to prevent
      ischemic stroke in very old people.

PMID- 16300877
TI  - Potential anticancer activity of litchi fruit pericarp extract against
      hepatocellular carcinoma in vitro and in vivo.
AB  - Litchi fruit pericarp (LFP) extract contains significant amounts of polyphenolic
      compounds, and exhibits powerful antioxidative activity against fat oxidation in
      vitro. The purpose of this study is to confirm the anticancer activity of LFP
      extract against hepatocellular carcinoma in vitro and in vivo, and to elucidate
      the mechanism of its activity. Human hepatocellular carcinoma cell line was
      tested in vitro for cytotoxicity, colony formation inhibition, and cell cycle
      distribution through flow cytometry after treatment with water-soluble crude
      ethanolic extract (CEE) from LFP. Murine hepatoma bearing-mice were fed doses of
      0.15, 0.3, and 0.6g/kg/day of water-soluble CEE in DH(2)O p.o. for 10 days,
      respectively, to test the anticancer activity and BrdU incorporation of cancer
      cells in vivo. LFP extract demonstrated a dose- and time-dependent inhibitory
      effect on cancer cell growth; IC(50) was 80microg/ml, and significantly inhibited
      colony formation in vitro, tumor growth and BrdU incorporation into cancer cells
      in vivo. The tumor inhibitory rates at doses of 0.15, 0.3, and 0.6g/kg/day were
      17.31% (P>0.05), 30.77% (P<0.05), and 44.23% (P<0.01), respectively. BrdU labeled
      tumor cells of treated animals were 11.80+/-2.79%, and were significantly lower
      than that in untreated controls (23.00+/-5.42%, P<0.05). Our findings showed that
      LFP extract exhibited potential anticancer activity against hepatocellular
      carcinoma in vitro and in vivo through proliferating inhibition and apoptosis
      induction of cancer cells.

PMID- 16300878
TI  - Aloe-emodin induced DNA damage through generation of reactive oxygen species in
      human lung carcinoma cells.
AB  - The DNA aggregation was found in aloe-emodin-induced H460 cell apoptosis in this
      study. Aloe-emodin (40microM)-induced DNA single strand breaks were observed by
      comet assay. Aloe-emodin induced decreases in the mRNA of DNA repair enzymes such
      as hMTH1, hOGG1 and APE. Although the activity of the radical-scavenging enzyme
      SOD was enhanced by aloe-emodin, the effects of aloe-emodin on H460 cell
      apoptosis were suspected to result from the prooxidant. These results suggest
      that aloe-emodin induced DNA damage through generation of reactive oxygen species
      in human lung carcinoma cells.

PMID- 16300879
TI  - Suppressive effect of Clostridium perfringens-produced heat-stable substance(s)
      on proliferation of human colon adenocarcinoma HT29 cells in culture.
AB  - Clostridium perfringens has been regarded as one of the intestinal bacteria
      increasing colon cancer risk. In previous studies, we have shown that the oral
      administration of C. perfringens culture medium can inhibit the mutagen-induced
      formation of pre-neoplastic lesions in rat colon, thus proposing the existence of
      factor(s) preventing colon tumorigenesis in this culture medium. However, the
      properties of effective factor(s) and the mechanism of this inhibitory action
      still remain to be investigated. Then, the effect of C. perfringens culture
      medium on human colon adenocarcinoma HT29 cells was examined. The exposure of
      HT29 cells to C. perfringens culture medium was found to suppress the
      proliferation of these cells probably through the reduction of immediate early
      gene egr-1 expression. These observations suggest that C. perfringens culture
      medium has a cytostatic action on colon tumor cells, which may be responsible for
      the prevention of pre-neoplastic formation in rat colon.

PMID- 16300880
TI  - Concentrations of ambient air particulates (TSP, PM2.5 and PM2.5-10) and ionic
      species at offshore areas near Taiwan Strait.
AB  - The concentrations of total suspended particulate (TSP), fine particles PM(2.5)
      (with aerodynamic diameter <2.5 microm), coarse particles PM(2.5-10) (with
      aerodynamic diameter 2.5-10 microm,), and water-soluble inorganic ions were
      studied at two offshore sampling sites, Taichung Harbor (TH) and Wuci Traffic
      (WT), near Taiwan Strait in central Taiwan during March 2004 to January 2005.
      Statistical analyses were also carried out to estimate the possible sources of
      particulate pollution. Experimental results showed that the average mass
      concentrations of TSP, PM(2.5) and PM(2.5-10) at TH and WT sampling sites were
      154.54 +/- 31.45 and 113.59 +/- 31.94 microg m(-3), 54.03 +/- 16.92 and 42.76 +/-
      12.52 microg m(-3), and 30.31+/- 9.79 and 24.16 +/- 7.27 microg m(-3),
      respectively. The dominant inorganic ions at two sampling sites were SO(4)(2-),
      NO(3)(-), and NH(4)(+) for TSP and PM(2.5), but that were Ca(2+), Cl(-), and
      Na(+) for PM(2.5-10). The concentrations of most particulates and inorganic ions
      were higher in winter at both two sampling sites, and were higher at TH than WT
      sampling site in each season. From statistical analysis, air-slake of crust
      surface, sea-salt aerosols, agriculture activities, coal combustion, and mobile
      vehicles were the possible emission sources of particulate pollution at TH and WT
      sampling sites.

PMID- 16300881
TI  - Ambient BTEX and MTBE in the neighborhoods of different industrial parks in
      Southern Taiwan.
AB  - This study assessed the concentrations of five volatile organic compounds (VOCs),
      including BTEX (the acronym for benzene, toluene, ethylbenzene, and xylene) and
      methyl tertiary-butyl ether (MTBE), in six different industrial park
      neighborhoods in southern Taiwan, including the Nei-Pu, Ping-Tung, Ping-Nan, Ren
      Wu, Lin-Yuan and Nan-Zi industrial parks. The concentrations of MTBE and BTEX
      ranged from undetectable to 145.6 microg/m3. Average MTBE-BTEX ratios of Nei-Pu,
      Ping-Tung, Ping-Nan, Ren-Wu, Lin-Yuan and Nan-Zi were (13.4:3.6:4.7:1.0:7.4),
      (2.9:1.0:1.7:1.3:2.9), (3.0:1.0:2.7:1.0:2.7), (5.2:1.0:8.6:1.7:4.9),
      (3.1:3.1:2.8:1.0:3.3) and (4.3:1.2:3.6:1.0:3.8), respectively. Moreover, average
      T/B ratios in Nei-Pu, Ping-Tung, Ping-Nan, Ren-Wu, Lin-Yuan and Nan-Zi were 1.3,
      1.7, 2.6, 8.6, 0.9 and 2.9, respectively. High T/B ratio (8.6) in the
      neighborhood of the Ren-Wu industrial park suggested that the emission of large
      additional sources of toluene from this industrial park, or the existence of
      major differences in the auxiliary fuels used. Average X/E ratios in Nei-Pu, Ping
      Tung, Ping-Nan, Ren-Wu, Lin-Yuan and Nan-Zi were 7.4, 2.2, 2.7, 2.9, 3.3 and 3.8,
      respectively. The lower X/E ratio (2.2) in the Ping-Tung neighborhood compared to
      elsewhere indicates an aged air parcel. Furthermore, principal component analysis
      also confirmed that the dominant influences in the six different industrial park
      neighborhoods were related to the emissions of MTBE, benzene and toluene.

PMID- 16300882
TI  - Use of rice straw and radiation-modified maize starch/acrylonitrile in the
      treatment of wastewater.
AB  - Graft copolymerization of acrylonitrile onto maize starch by a simultaneous
      irradiation technique using gamma-rays as the initiator was studied with regard
      to the various parameters of importance: the monomer-to-maize starch ratio and
      total dose (kGy). The water absorption of the modified maize starch was measured.
      The starch modified by acrylonitrile gives low water absorbance. Conversion of
      the copolymer to the amidoxime form gives high swelling. The gel (%) and the
      grafting efficiency were measured. An investigation was carried out to study the
      adsorption of basic violet 7, basic blue 3, direct yellow 50 and acid red 37 from
      aqueous solutions by the water-insoluble modified starch containing amidoxime
      groups and rice straw. The effects of initial pH of the solution, pollutant
      concentration and treatment time on the adsorption were studied and it was found
      that the maximum adsorption was at 1:2 (starch/acrylonitrile) at irradiation dose
      30 kGy.

PMID- 16300883
TI  - Prediction of heat of formation and related parameters of high energy materials.
AB  - Heat of formation is one of the most important parameters in the performance
      prediction of explosive and propellant formulations and their individual
      ingredients. This paper reports the development of user-friendly computer code
      for the prediction of heat of formation based on two approaches. In first
      methodology, the logic of Benson's Group additivity method and in the second
      method, the logic of Pedley method was used for predicting the heats of formation
      of high energy materials (HEMs). The predicted heats of formation by Benson
      method for various classes of high energy materials gave deviation in the range
      of 2-10%, whereas nearly 10-15% deviation was observed using Pedley methodology
      in comparison to experimental values. The linear regression coefficient values
      (R(2)) of 0.9947 and 0.9637 are obtained for heat of formation values predicted
      by this code using methodologies I and II, respectively. The newly developed code
      LOTUSES (version 1.3) has been validated by calculating the heats of formation of
      standard explosives such as TNT, pentaerythritol tetranitrate (PETN), RDX, HMX,
      etc., To the best of our knowledge, no such code is reported in literature which
      can predict heats of formation values integrated with performance parameters of
      HEMs belonging to all categories of organic compounds viz. aliphatic, aromatic
      and heterocyclic materials. The code can also be used to obtain parameters such
      as velocity of detonation, C-J pressure, volume of explosion products, power
      index, temperature of explosion and oxygen balance of HEMs. The code has been
      developed in Visual Basic having enhanced Windows environment. This software
      namely LOTUSES 1.3 is an updated version of the earlier ones namely LOTUSES 1.1
      and 1.2 which do not cater for the calculation of heat of formation and
      temperature of explosion of HEMs. LOTUSES 1.3 is, therefore, a totally integrated
      software for computing most of the vital parameters of HEMs requiring mainly the
      molecular structural information of an explosive under consideration.

PMID- 16300884
TI  - Electrochemical pilot-scale plant for oil field produced wastewater by M/C/Fe
      electrodes for injection.
AB  - Oil field produced water by separated with crude oil were treated by an
      electrochemical process in laboratory pilot-scale plant, using double anodes with
      active metal (M) and graphite (C) and iron as cathode and a noble metal content
      catalyst with big surface. Due to the strong oxidizing potential of the chemicals
      produced (Cl(2), O(2), OCl(-), HO and so on), when the wastewater pass through
      the laboratory pilot-scale plant the organic pollutants including bacteria were
      oxidized and coagulated by produced M(n+) ion. It can be concluded that the
      catalytic electrochemical treatment of oil field produced wastewater is
      effective. Both chemical oxygen demand (COD) and biochemical oxygen demand (BOD)
      were reduced by over 90% in 6 min, suspense solids (SS) by 99%, Ca(2+) content by
      22%, corrosion rate by 98% and bacteria (sulphate reducing bacteria (SRB),
      saprophytic bacteria (TGB) and iron bacteria) by 99% in 3 min under 15V/120A.
      These results indicate that this catalytic electrochemical method could be used
      for effective oil field wastewater treatment for injection purpose.

PMID- 16300885
TI  - Methods to improve electrochemical treatment effect of dye wastewater.
AB  - Several methods, including changing electrolyte concentration, temperature,
      stirring, and voltage were studied to improve the degradation effect of
      electrochemical treatment in dye wastewater. In addition, nanophase TiO2 catalyst
      and Co-Bi-PbO2/Ti anode have been prepared to expedite color removal. Enhancement
      of temperature leads to proportional increase of color removal. As for voltage,
      at low levels its increase could greatly improves color removal. After voltage
      reaches about 3.0 V, its improvement effect declines quickly. The influence of
      electrolyte concentration and aerating on color removal are similar to that of
      voltage. So it favored to degrade organic pollutants using high salt
      concentration, high voltages and large electric current to improve treatment
      effect. However, the efficiency of energy supplied during electrolysis decreases.
      A nonlinear model is established to evaluate the influence of electrolyte
      concentration and voltage on color removal. The model agrees with the experiment
      data very well. It is suggested by the simulation result of this model that
      electrolysis degradation should better be carried out at about 3.0 V, in 0.01 M
      Na2SO4 concentration for high energy efficiency. Additionally, either catalyst or
      Co-Bi-PbO2/Ti anode brings about 0.15 times more color removal without increasing
      electric current. Together, they could bring forth some 0.22 times higher color
      removal.

PMID- 16300886
TI  - Development of a pentylenetetrazole-induced seizure model to evaluate kinase
      inhibitor efficacy in the central nervous system.
AB  - c-Jun N-terminal kinases (JNKs) are implicated in cell death in neurodegenerative
      disorders. Therefore, JNK inhibitors could act as neuroprotective agents. To
      evaluate potential candidates, reproducible and quantitative CNS in vivo models
      are required. To that end, a pentylenetetrazole-induced seizure model was
      explored. c-Jun phosphorylation was detected in hippocampal extracts by blotting
      c-Jun immunoprecipitates with phosphorylation-specific antibodies.
      Pentylenetetrazole administration induced rapid and reproducible increases in c
      Jun phosphorylation. However, special attention had to be paid to the composition
      of the extraction buffer to ensure stabilization of protein phosphorylation, as
      demonstrated using internal standards of phosphorylated recombinant c-Jun. As JNK
      and its upstream activator MKK4 are activated by phosphorylation, these events
      were also evaluated. In principle, kinase inhibitors could act at the level of
      JNK or upstream kinases to inhibit c-Jun phosphorylation. MKK4 phosphorylation
      was dramatically increased in response to pentylenetetrazole but, again, only
      when appropriate phosphatase inhibitors were in the extraction buffer. In
      contrast, JNK was found to be constitutively phosphorylated and unaltered upon
      pentylenetetrazole treatment. The JNK inhibitor SP600125 was shown to inhibit c
      Jun phosphorylation without affecting MKK4 phosphorylation. Our procedures enable
      analysis of JNK pathway signalling in a CNS model and, also, should be applicable
      to that of other protein phosphorylation events in vivo.

PMID- 16300887
TI  - Ketogenic diet decreases the level of proenkephalin mRNA induced by kainic acid
      in the mouse hippocampus.
AB  - The ketogenic diet (KD) has been used to control medically refractory epilepsy in
      children for more than 80 years. Despite the clinical efficacy of the KD, its
      underlying bases are still obscure. Previous work from our laboratory has
      established that the KD has an antiepileptic and neuroprotective effect in the
      kainic acid (KA)-induced seizure model. The neuronal excitation caused by KA
      leads to increases in the expression of a variety of genes, including immediate
      early genes and opioid peptides derived from proenkephalin (PENK) and
      prodynorphin (PDYN). In particular, the up-regulated PENK gene that is induced by
      KA in the hippocampal dentate granule cells has proconvulsant properties. PENK is
      regulated by the c-jun amino-terminal kinase (JNK) signaling pathway, the crucial
      role of which is involved in the regulation of transcription factors, such as Jun
      and Fos. In the present study, we examined the effect of the KD on the increase
      of PENK, Fos, Jun, AP-1 DNA-binding activity and JNK gene expression induced by
      KA in the mouse hippocampus. Using in situ hybridization and northern blot
      analysis, we found that the KD significantly decreases the level of PENK gene
      expression induced by KA of the granular cells in the hippocampus. In addition,
      we have also found that KD diminished KA-induced AP-1 DNA-binding activity, Fos
      and Jun expression, and phoshorylated form of the three types of JNKs. These
      results suggest that the KD suppresses KA-induced activation of JNK signaling
      pathways, followed by a decrease of PENK gene expression in the hippocampus,
      thereby resulting in antiepileptic effects.

PMID- 16300888
TI  - Increased opioid receptor binding and G protein coupling in the accumbens and
      ventral tegmental area of postnatal day 2 rats.
AB  - In some regions of the developing rat brain such as the nucleus accumbens (Acb),
      mu opioid (MOP) receptor specific binding in the perinatal period exceeds that in
      the adult. To investigate the significance of these developmental changes, MOP
      and nociceptin/orphanin FQ (NOP) receptor binding and G protein coupling as
      determined by GTPgammaS binding experiments were examined in mesolimbic regions
      of postnatal day 2 (P2) pups and compared to those of their dams. Acb of the P2
      pup exhibited 2-fold greater MOP receptor specific binding than that of the dam.
      In the ventral tegmental area (VTA), NOP specific binding was about 2-fold higher
      in the P2 pup. A correlation was found between MOP and NOP binding and their
      coupling to G protein on dam and P2 pup brain sections. However, the magnitude of
      increases in MOP and NOP receptor G protein coupling to G protein in P2 pups
      exceeded the 2-fold differences in binding between pups and dams. Furthermore,
      the amplitude of the MOP receptor G protein coupling in female P2 Acb was greater
      than increases in male P2 pup Acb. Differences in MOP and NOP binding and G
      protein coupling in other mesolimbic regions between P2 pups and dams were rarely
      observed. The data indicate that greater binding and G protein coupling of MOP
      and NOP receptors occur in discrete, mesolimbic regions of P2 pups when compared
      to their dams. It may be of significance that these brain regions, Acb and VTA,
      are undergoing maturation on P2.

PMID- 16300889
TI  - Effects of gender, age, and body parameters on the ventricular volume of Korean
      people.
AB  - The purpose of this study was to measure the average ventricular volume of normal
      Koreans (aged in their 20s or 40s) and to analyze the effects of gender, age, and
      body parameters, such as height and weight on ventricle size. Magnetic resonance
      brain images were recorded for 118 people in their 20s (58 men, 60 women) and 100
      in their 40s (41 men, 59 women). Using automatic and manual segmentation
      techniques, the volumes of the lateral and the third and fourth ventricles were
      calculated. To investigate the different and interactive effects of gender and
      age on ventricular volume, two-way analysis of variance (ANOVA) with gender and
      age as independent variables was carried out. Multiple regression analysis was
      used to investigate the effect of body parameters, such as height and weight
      according to gender on changes in ventricular volume. The average ventricular
      volume for people in their 20s was 16.2 cm3, and that for people in their 40s was
      24.9 cm3. The average ventricular volume for men and women was 22.9 and 18.1 cm3,
      respectively. The average ventricular volume for men was greater than that for
      women, and that for people in their 40s was greater than that in their 20s.
      Enlargement of the ventricles on aging was more markedly observed in men than in
      women. There was a positive relationship between the body height and ventricular
      volume for men but not for women. There was no relationship between weight and
      ventricular volume for either men or women.

PMID- 16300890
TI  - Calcium oscillations in type-1 astrocytes, the effect of a presenilin 1 (PS1)
      mutation.
AB  - Stimulation of type-1 astrocytes, by a number of agonists, has been shown to
      increase cytosolic Ca2+ concentrations in an oscillatory manner. However, it is
      unknown how these are driven or altered by aging, injury or disease. Therefore,
      we characterized the signaling properties of rat type-1 astrocytes in monolayer
      cultures. Ca2+ responses were recorded in astrocytes stimulated with ATP or
      glutamate. Oscillations were evident in cultures at 3 days in vitro (DIV 3) with
      a peak percentage (26%) of cells responding by DIV 7. The presence or absence of
      serum in the culture medium did not influence this percentage. Likewise, long
      term culture (DIV 30+) did not increase the oscillating cell numbers. ATP was
      found to have a more potent effective dose (50 microM) than glutamate (10 mM).
      Membrane potential was recorded with fluorescent voltage-sensitive dye (membrane
      potential dye for FLIPR) and was similar regardless of the culture age and
      intracellular Ca2+ response. This suggests that mechanisms associated with the
      intracellular release of Ca2+ from endogenous Ca2+ stores, rather than ion fluxes
      across the plasma membrane, may contribute to the oscillations in the astrocytes.
      In order to identify a possible pathological significance of this response, we
      transfected astrocytes with wild-type presenilin (PS1) as well as PS1 harboring a
      mutation linked to familial Alzheimer's disease (FAD). PS mutation expressing
      astrocytes oscillated at lower ATP and glutamate concentrations when compared to
      wild-type PS1 expressing astrocytes. This indicates that PS1 mutation may
      introduce aberrations in the intracellular Ca2+ mobilization in astrocytes
      contributing to the accelerated pathogenesis in FAD.

PMID- 16300891
TI  - Expression patterns of neurexin-1 and neuroligins in brain and retina of the
      chick embryo: Neuroligin-3 is absent in retina.
AB  - Neuroligins (NLs) constitute a family of cell-surface proteins that interact with
      neurexins (beta-Nxs), another class of neuronal cell-surface proteins, one of
      each class functioning together in synapse formation. The localization of the
      various neurexins and neuroligins, however, has not yet been clarified in
      chicken. Therefore, we studied the expression patterns of neurexin-1 (Nx-1) and
      neuroligin-1 and -3 during embryonic development of the chick retina and brain by
      reverse-transcriptase polymerase chain reaction (RT-PCR) and in situ
      hybridization (ISH). While neurexin-1 increased continuously in both brain and
      retina, the expression of both neuroligins was more variable. As shown by ISH, Nx
      1 is expressed in the inner half retina along with differentiation of ganglion
      and amacrine cells. Transcripts of NL-1 were detected as early as day 4 and
      increased with the maturation of the different brain regions. In different brain
      regions, NL-1 showed a different time regulation. Remarkably, neuroligin-3 was
      entirely absent in retina. This study indicates that synaptogenetic processes in
      brain and retina use different molecular machineries, whereby the neuroligins
      might represent the more distinctly regulated part of the neurexin-neuroligin
      complexes. Noticeably, NL-3 does not seem to be involved in the making of retinal
      synapses.

PMID- 16300892
TI  - Differential effects of morphine- and cocaine-induced nNOS immunoreactivity in
      the dentate gyrus of hippocampus of mice lacking mu-opioid receptors.
AB  - This study investigated the expression of nNOS after repeated morphine or cocaine
      administration in order to determine if nNOS (neuronal nitric oxide synthase) is
      involved in the morphine- or cocaine-induced behavioral sensitization in mu
      opioid receptor knockout (MOR(-/-)) mice. Higher numbers of nNOS-positive cells
      were observed in the dentate gyrus of the hippocampus (DG) of the wild-type
      (MOR(+/+)) mice repeatedly treated with either morphine or cocaine than in the
      saline treated MOR(+/+) mice (morphine, +122%; cocaine, +82%). Moreover, the MOR(
      /-) mice also showed significantly higher morphine- or cocaine-induced nNOS
      expression levels in the DG than in the saline treated MOR(+/+) mice (morphine,
      +234%; cocaine, +54%). The MOR(-/-) mice showed a significantly higher morphine
      induced nNOS expression level (+103%) or a lower cocaine-induced nNOS expression
      level (+38%) in the DG than in the morphine- or cocaine-treated MOR(+/+) mice.
      These results suggest that morphine and cocaine sensitization is differentially
      regulated by the mu-opioid receptors in MOR(-/-) mice via the nNOS systems in the
      DG.

PMID- 16300893
TI  - Aquaporin 1 expression in cystic hemangioblastomas.
AB  - Hemangioblastomas of the central nervous system (CNS) become clinically manifest
      through the development of huge associated cysts. The mechanism underlying these
      fluid collections is as yet largely unexplained. Aquaporins (AQPs) are cell
      proteins responsible for transmembrane water transport that have been extensively
      studied in the last 10 years. We analyzed AQP1 water channel expression by an
      immunostaining technique in ten specimens of operated cerebellar cystic
      hemangioblastomas, for which complete clinical and follow-up records were
      available. Tumour and associated cyst volumes were determined by neuroimaging and
      then compared with immunohistochemical scores. Stromal cancer cells showed
      surprisingly high AQP1 expression, and huge cyst volume development showed
      correlation with higher immunostaining scores. Heavy AQP1 expression in cystic
      hemangioblastomas could shed new light on the mechanisms of satellite cyst
      development.

PMID- 16300894
TI  - Moderate state-anxiety differently modulates visual and auditory response times
      in normal- and very low trait-anxiety subjects.
AB  - Because relationships between mood states, personality and motor performances
      remain ambiguous, we investigated in very low trait-anxiety (VLTA) and normal
      trait-anxiety (NTA) subjects, the effects of moderate state-anxiety, tension and
      fatigue induced by the video-recorded Stroop Color-Word Interference Test on
      reaction time and movement time in visual and auditory tasks. Our results show
      that visual response time performances were improved in NTA subjects, while
      auditory response time performances were improved in VLTA subjects. In both
      groups, improvement of performance occurred at the reaction time and movement
      time level. Our results show that allocation of attentional resources can be
      modulated by personality traits, such as trait-anxiety, and furthermore highlight
      personality and individual differences as regards to the human/environment
      interaction.

PMID- 16300895
TI  - Regulation of phosphorylation of NMDA receptor NR1 subunits in the rat
      neostriatum by group I metabotropic glutamate receptors in vivo.
AB  - Group I metabotropic glutamate receptors (mGluRs) are Galphaq-protein-coupled
      receptors and are densely expressed in medium-sized spiny projection neurons of
      the neostriatum. Among different subtypes of glutamate receptors, group I mGluRs
      have been demonstrated to actively interact with the ionotropic glutamate
      receptor N-methyl-d-aspartate (NMDA) subtypes for regulating various forms of
      cellular activities and synaptic plasticity. In this study, the possible role of
      group I mGluRs in regulating serine phosphorylation of NMDA receptor NR1 subunits
      in the neostriatum was investigated in vivo. We found in chronically cannulated
      rats that injection of the group I mGluR agonist 3,5-dihydroxyphenylglycine
      (DHPG) into the dorsal striatum (caudate putamen) significantly increased
      phosphorylation of the two serine residues (serine 896 and serine 897) on the
      intracellular C-terminus of the NR1. The increase in NR1 phosphorylation was dose
      dependent and DHPG had no effect on basal levels of NR1 proteins. Intrastriatal
      infusion of the group I mGluR antagonist N-phenyl-7
      (hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC) significantly
      attenuated the DHPG-stimulated NR1 phosphorylation. Pretreatment with the mGluR5
      antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) also produced
      the same effect. These data suggest that group I mGluRs, likely mGluR5 subtypes,
      possess the ability to upregulate protein phosphorylation of NMDA receptor NR1
      subunits in striatal neurons in vivo.

PMID- 16300896
TI  - Early evidence of a regulated response to hypoxaemia in sheep that preserves the
      brain cortex.
AB  - Hypoxaemia consequent to inspired carbon monoxide (CO), and to other causes,
      often does not injure the brain cortex. At least five types of brain and heart
      protective cardiovascular response to hypoxaemia have been reported. The
      underlying mechanism is unknown. The present study was designed to test the
      hypothesis that the reaction to inspired CO involves the amygdala as this
      structure is thought to be central to stress responsivity; involvement would
      support the additional hypothesis that the somatic response to CO-hypoxaemia is
      regulated. Eighteen ewes were randomly allocated to control and two CO groups.
      The CO groups were exposed to 1% CO for 120 min and killed either 5 or 15 days
      later. This exposure caused isolated white matter brain injury and a transient
      increase in protein-kinase C (gamma) activity in the pyramidal neurons in the
      nuclei of the central and basal-lateral amygdala and in the neurons of the audio
      cortex (p < 0.05). This was associated with evidence of a sympathetic response.
      It would seem reasonable to hypothesise both that the amygdala is important in
      the processes by which the hypoxaemic effects of CO on the brain are prevented,
      delayed and/or mitigated and that these processes are regulated.

PMID- 16300897
TI  - Cathepsin L cysteine proteinase in the diagnosis of bovine Fasciola gigantica
      infection.
AB  - Cathepsin L cysteine proteinase from Fasciola gigantica was evaluated for its
      potential in the early prepatent detection of this helminth infection in bovine
      calves. Five cross-bred bovine calves were experimentally infected with 400
      metacercariae/calf and evaluated for anti-cathepsin L antibody response. F.
      gigantica infection in these calves could be detected 4 weeks post-infection
      using an ELISA, dipstick ELISA and Western blotting with 100% sensitivity. The
      antigen was also used to detect F. gigantica field infection in cattle, by
      screening 256 sera of these animals by an ELISA, which demonstrated an overall
      infection rate of 26.95%. Preliminary studies showed that F. gigantica cathepsin
      L cysteine proteinase does not cross-react with Paramphistomum epiclitum,
      Gigantocotyle explanatum and hydatid cyst antigens. However, extensive studies on
      the cross-reactivity of this antigen with related helminth parasites of cattle
      and buffaloes are required, before this antigen can be considered suitable for
      immuno-diagnosis of fasciolosis in these ruminants.

PMID- 16300898
TI  - The effect of an experimentally induced acute mastitis on the test results of an
      Ostertagia ostertagi milk ELISA.
AB  - Antibody levels against Ostertagia ostertagi in the milk are a promising
      parameter to identify dairy cows or herds with production losses due to
      gastrointestinal nematodes. However, milk antibody levels can be influenced by
      udder-related factors. In this study, the effect of an experimentally induced
      mastitis on the test results (ODR) of a milk O. ostertagi ELISA was investigated.
      Twenty-five cows that were naturally infected with gastrointestinal nematodes,
      were inoculated in their left udder quarters with Escherichia coli P4:O32 and
      quarter milk samples were collected at several intervals from 24 h before until
      144 h after experimental infection. The effect of the contribution of milk from
      one or more infected quarters on the bulk tank milk ODR was estimated, based on a
      titration experiment. The mean O. ostertagi antibody levels of the infected udder
      quarters were significantly (P < 0.001) higher than those of the uninfected udder
      quarters at each sampling time post-infection. The largest difference was
      observed at 24 h post-infection with a mean difference of 0.251 ODR (95%CI:
      0.172; 0.330). There was also a significant increase (P < 0.001) in total IgG
      levels with the largest difference being observed at 24 h post-infection. Highly
      significant (P < 0.005) correlation coefficients were observed between O.
      ostertagi ODR, total IgG ODR, Na+ and Cl- ion concentration and log transformed
      somatic cell counts at 24 h post-infection. The results demonstrate that an acute
      mastitis causes a flow of specific and non-specific antibodies from serum to milk
      with a subsequent increase in the O. ostertagi ODR values. The effect of the
      contribution of milk from infected quarters on the bulk tank milk O. ostertagi
      ODR was estimated to be minor if the relative number of infected quarters is
      small (< 3%).

PMID- 16300899
TI  - Colorectal cancer metastases affect the biochemical characteristics of the human
      liver beta-adrenoceptor-G-protein-adenylate cyclase system.
AB  - The sympathetic-catecholamine system is involved in the regulation of hepatic
      metabolic pathways mainly through cAMP-linked beta2-adrenoceptors (beta2-ARs) in
      humans and to a lesser extent through cAMP-independent mechanisms, but no
      information is available about the possible biochemical changes of beta2-ARs and
      their signalling pathways in human colorectal cancer (CRC) and colorectal cancer
      hepatic metastases (CRCHM). Changes in density and distribution of beta-ARs as
      well as in post-receptor signalling components were studied in membranes of human
      liver with CRCHM, and for comparison, in membranes of nonadjacent, non-metastatic
      human liver (NA-NM) obtained from 13 patients, using binding and competition
      binding studies. Studies were also carried out using normal and cancerous human
      colon tissues. In CRCHM, the density of beta-ARs (B(max)) was significantly
      reduced, compared to NA-NM liver tissues (40.09+/-2.83 vs. 23.09+/-3.24 fmol/mg
      protein; P<0.001). A similar decrease in the beta-AR density was observed in the
      colon with primary colorectal cancer compared to healthy colon (37.6+/-2.2 vs.
      23.8+/-3.5 fmol/mg protein), whereas the affinity of ICYP binding to the receptor
      remained unaffected. Desensitized beta-ARs were uncoupled from stimulatory G
      protein (G(S)), as total density of beta-adrenoceptors in the high affinity state
      was significantly reduced. Concomitantly, CRCHM elicited decrease in the
      catalytic adenylate cyclase (AC) activity (cAMP formation) in response to
      isoproterenol plus GTP or forskolin or NaF. In NA-NM and CRCHM liver, the
      inhibition-concentration curves of ICI 118.551 showed the presence of a
      homogeneous population of the beta2-AR subtypes. Neither the binding patterns nor
      the inhibition constant (K(i)) of ICI 118.551 were altered in CRCHM. In CRCHM,
      the hepatic beta-AR-G-protein(s)-AC signalling system was markedly impaired,
      thus, these changes may well influence beta-AR-mediated functions in both organs.

PMID- 16300900
TI  - Ionic interventions that alter the association of troponin C C-domain with the
      thin filaments of vertebrate striated muscle.
AB  - The regulatory complex of vertebrate skeletal muscle integrates information about
      cross-bridge binding, divalent cations and other intracellular ionic conditions
      to control activation of muscle contraction. Relatively little is known about the
      role of the troponin C (TnC) C-domain in the absence of Ca2+. Here, we use a
      standardized condition for measuring isometric tension in rabbit psoas skinned
      fibers to track TnC attachment and detachment in the absence of Ca2+ under
      different conditions of ionic strength, pH and MgATP. In the presence of MgATP
      and Mg2+, TnC detaches more readily and has a 1.5- to 2-fold lower affinity for
      the intact thin filament at pH 8 and 250 mM K+ than at pH 6 or in 30 mM K+;
      changes in affinity are fully reversible. The response to ionic strength is lost
      when Mg2+ and MgATP are absent, whereas the response to pH persists, suggesting
      that weaker electrostatic TnC-TnI-TnT interactions can be overridden by strongly
      bound cross-bridges. In solution, titration of a fluorescent C-domain mutant
      (F154W TnC) with Mg2+ reveals no significant changes in Mg2+ affinity with pH or
      ionic strength, suggesting that these parameters influence TnC binding by acting
      directly on electrostatic forces between TnC and TnI rather than by changing Mg2+
      binding to C-domain sites III and IV.

PMID- 16300901
TI  - What can research on schizophrenia tell us about the cognitive neuroscience of
      working memory?
AB  - Work with individuals with lesions to specific brain regions has long been used
      to test or even generate theories regarding the neural systems that support
      specific cognitive processes. Work with individuals who have neuropsychiatric
      disorders that also involve neurobiological disturbances may be able to play a
      similar role in theory testing and building. For example, schizophrenia is a
      psychiatric disorder thought to involve a range of neurobiological disturbances.
      Further, individuals with schizophrenia are known to suffer from deficits in
      working memory, meaning that examining the work on the neurobiology of working
      memory deficits in schizophrenia may help to further our understanding of the
      cognitive neuroscience of working memory. This article discusses the pros and
      cons of extrapolating from work in schizophrenia to models of healthy working
      memory function, and reviews the literature on working memory function in
      schizophrenia in relationship to existing human and non-human primate models of
      the cognitive neuroscience of working memory.

PMID- 16300902
TI  - Mixed antagonistic effects of bilobalide at rho1 GABAC receptor.
AB  - Bilobalide was found to be a moderately potent antagonist with a weak use
      dependent effect at recombinant human rho(1) GABA(C) receptors expressed in
      Xenopus oocytes using two-electrode voltage clamp methodology. Antagonism of
      bilobalide at homomeric rho(1) GABA(C) receptors appeared to be mixed. At low
      concentration, bilobalide (3 microM) caused a parallel right shift and
      surmountable GABA maximal response of the GABA dose-response curve characteristic
      of a competitive antagonist. At high concentrations, bilobalide (10-100 microM)
      caused nonparallel right shifts and reduced maximal GABA responses of GABA dose
      response curves characteristic of a noncompetitive antagonist. The potency of
      bilobalide appears to be dependent on the concentrations of GABA and was more
      potent at lower GABA concentrations. The mechanism of action of bilobalide at
      rho(1) GABA(C) receptors appears to be similar to that of the chloride channel
      blocker picrotoxinin.

PMID- 16300903
TI  - Madness explained: why we must reject the Kraepelinian paradigm and replace it
      with a 'complaint-orientated' approach to understanding mental illness.
AB  - This article is a synopsis of the argument outlined in my book Madness explained:
      Psychosis and human nature, in which I describe a new paradigm (which might be
      called a 'complaint-orientated' approach) for understanding the psychotic
      disorders, the most disabling forms of psychiatric illness. Despite extensive
      efforts to study the genetics, pathophysiology and neuropsychology of the
      psychoses, replicable findings have been rare. I argue that this is because the
      phenomena concerned have been poorly defined. Since the end of the 19th century,
      research into the psychoses has been dominated by the system of classification
      first proposed by the German psychiatrist Emil Kraepelin, which assumes that the
      severe mental illnesses fall into discrete types such as 'schizophrenia' and
      'manic depression', and that there is a clear dividing line between madness and
      normal functioning. However, Kraepelinian diagnoses fail all empirical tests of
      their validity. For example, they do not identify patients with common symptoms,
      with common aetiologies, who respond to specific treatments. I suggest that we
      therefore need to abandon psychiatric diagnoses altogether and must instead
      attempt to explain the specific complaints ('symptoms') that patients bring to
      our attention. These include hallucinations, delusional beliefs, thought and
      communication disorders, which are much more widely experienced than was
      previously thought (for example, about 10% of the population have experienced
      hallucinations). I show that recent psychological research has revealed much
      about the mechanisms underlying each of these complaints. For example, auditory
      hallucinations occur when the individual mistakes inner speech for an external
      stimulus, and delusions appear to be the product of abnormal inferential
      processes. The new approach has implications for aetiology. For example,
      researchers working within the Kraepelinian paradigm have often assumed that the
      psychoses are endogenous. However, there is compelling evidence that the risk of
      experiencing psychotic complaints is influenced by adverse environmental factors
      such as insecure attachment relations and exposure to sexual and other kinds of
      trauma. These associations are relatively easy to understand once the
      psychological mechanisms leading to specific complaints are known. When all of
      the psychotic complaints have been explained, there will be no 'schizophrenia' or
      'manic depression' left behind awaiting explanation. The approach that I advocate
      is not only more scientific than the Kraepelinian approach, but also more humane.
      In contrast to the Kraepelinian approach, which has encouraged disrespect for
      patients' experiences, it encourages us to treat patients as rational agents and
      to take what they say seriously.

PMID- 16300904
TI  - Arsenic and nickel: Unavoidable constituents of our everyday diet.

PMID- 16300905
TI  - Neuropharmacology of cognition and memory: a unifying theory of neuromodulator
      imbalance in psychiatry and amnesia.
AB  - The case of HM, a man with intractable epilepsy who became amnesic following
      bilateral medial temporal lobe surgery nearly half a century ago has instigated
      ongoing research and theoretical speculation on the nature of memory and the role
      of the hippocampus. Neuropsychological testing showed that although HM had
      extensive anterograde memory loss he could still acquire motor and cognitive
      skills implicitly, but could not remember the context of this learning. This has
      lead to declarative and procedural descriptions of the memory process.
      Cholinergic and monoaminergic neurotransmitter systems have also been implicated
      in the memory process and anticholinergic drugs traditionally have been
      associated with impairment of declarative memory. The cholinergic hypothesis of
      Alzheimer's disease is a classic example of an application of these
      neuropharmacological findings. In schizophrenia, preattentive deficits have been
      amply demonstrated by unconscious priming studies. Memory processes are also
      impaired in these patients. Dopamine, glutamate and even cholinergic dysfunction
      has been implicated in the clinical picture of schizophrenia. The present paper
      will attempt to bring together both the anatomical and pharmacological data from
      these disparate fields of research under a cohesive theory of cognition and
      memory. A hypothesis is presented for an inverse relationship between
      monoaminergic and cholinergic systems in the modulation of implicit (unconscious)
      and explicit (conscious) cognitive processes. It is postulated that muscarinic
      cholinergic receptors and monoaminergic systems facilitate unconscious and
      conscious processes, respectively, and they disfacilitate conscious and
      unconscious processes, respectively (the purported inverse relationship). In
      fact, the muscarinic and monoaminergic modulations of a neural network are
      proposed to be finely balanced such that, if, the activity of one receptor system
      is modified then this by necessity has effects on the other system. It takes into
      account receptor subtypes and their effects mediated through excitatory and
      inhibitory G-protein complexes. For example, m1/D2 and D1/m4 paired receptor
      subtypes, colocalized on separate neurons would have opposing functional effects.
      A theory is then presented that the critical underlying pathophysiology of
      schizophrenia involves a hypofunctional muscarinic cholinergic system, which
      induces abnormal facilitation of monoaminergic subsystems such as dopamine (e.g.,
      a decrease in m1R function would potentiate D2R function). This extends the idea
      of an inverted U function for optimal monoaminergic concentrations. Not only
      would this impair unconscious preattentive processes, but according to the
      hypothesis, explicit cognition as well including memory deficits and would
      underlie the mechanism of psychosis. Contrary to current thinking a different
      view is also presented for the role of the hippocampus in the memory process. It
      is postulated that long-term explicit memory traces in the neocortex are laid
      down by phasic coactivation of forebrain projecting monoaminergic systems above
      some basal firing rate, such as the rostral serotonergic raphe, which projects
      diffusely to the cortex and according to a modified Hebbian principle. This is
      the proposed principal function of the hippocampal theta rhythm. The phasic
      activation of the cholinergic basal forebrain is mediated by projections from a
      separate cortical structure, possibly the lateral prefrontal cortex. Phasic
      muscarinic receptor activation is proposed to strengthen implicit memory traces
      (at a synaptic level) in the neocortex. Thus, the latter are spared by medial
      temporal surgery explaining the dissociation of explicit from implicit memory.

PMID- 16300906
TI  - Cytotoxicity of cycloartane triterpenoids from aerial part of Cimicifuga foetida.
AB  - Our previous study had demonstrated cytotoxicity of EtOAc fraction from aerial
      part of Cimicifuga foetida on various cancer cell lines. In the present study, we
      investigated the cytotoxicity of five cycloartane triterpenoids isolated from the
      EtOAc fraction. Compounds (1,2,3) showed moderate cytotoxic activity on R-HepG2
      cells and drug resistant sub line R-HepG2 but exhibited less toxicity against
      primary cultured normal mouse hepatocytes. Compounds (4) and (5) were inactive on
      all tested cell lines.

PMID- 16300907
TI  - Work-family conflicts and drinking behaviours among employed women and men.
AB  - OBJECTIVE: To examine the relationship between work-family conflicts and drinking
      behaviours among women and men, and to discover whether the relationship remains
      the same after taking into account family structure and socio-economic status.
      METHOD: Cross-sectional surveys were carried out by postal questionnaires in 2001
      and 2002 among female and male municipal employees aged 40-60, of Helsinki,
      Finland; 4228 women and 1043 men participated, with a response rate of 66%.
      Dependent variables were heavy drinking-for men >12 standard portions per week
      and for women >9 portions per week; weekly binge drinking including 6 or more
      portions per occasion; and problem drinking, as measured by the CAGE
      questionnaire. Independent variables were work-to-family conflicts and family-to
      work conflicts. Covariates were age, family structure, education, income, and
      occupational class. RESULTS: Work-family conflicts were strongly related to
      problem drinking among both women and men and also associated with heavy drinking
      among women. Taking family structure and socio-economic status into account did
      not markedly change the relationship between work-family conflicts and heavy
      drinking among women, but strengthened slightly the association with problem
      drinking among both women and men. CONCLUSIONS: Work-family conflicts are
      particularly important issues in problem drinking among men and women and also in
      heavy drinking among women. Improving the balance between work and family may be
      a way to prevent problem drinking.

PMID- 16300908
TI  - A new vector for controllable expression of an anti-HER2/neu mini-antibody
      barnase fusion protein in HEK 293T cells.
AB  - Tumor-targeted vectors with controllable expression of therapeutic genes and
      specific antitumor antibodies are promising tools for the reduction of malignant
      tumors. Here we describe a new plasmid for the eukaryotic expression of an anti
      HER2/neu mini-antibody-barnase fusion protein (4D5 scFv-barnase-His(5)) with an
      NH(2)-terminal leader peptide. The 4D5 scFv-barnase-His(5) gene was placed
      downstream of the tetracycline responsive-element minimal promoter in the vector
      using the Tet-Off gene-expression system. The Bacillus amyloliquefaciens
      ribonuclease barnase is toxic for the host cells. To overcome this problem,
      barstar gene under its own minimal cytomegalovirus promoter was used in designed
      vector. Barstar inhibits the background level of barnase in the cells in the
      presence of tetracycline in culture medium. The HEK 293T cells were transfected
      with the designed vector, and the 4D5 scFv-barnase-His(5) fusion protein was
      identified by anti-barnase antibodies in cell culture medium and after
      purification from cell lysates using metal-affinity chromatography. The
      overexpression of the anti-HER2/neu mini-antibody-barnase fusion protein
      decreased the intensity of fluorescence of HEK 293T cells co-transfected with the
      generated plasmid and a plasmid containing the gene of enhanced green fluorescent
      protein (pEGFP-N1), in comparison with the intensity of fluorescence of HEK 293T
      cells transfected with pEGFP-N1, in the absence of tetracycline in the medium.
      The effect of the 4D5 scFv-barnase-His(5) on EGFP fluorescence indicates that the
      introduced barnase functions as a ribonuclease inside the cells. The anti
      HER2/neu mini-antibody could be used to deliver barnase to HER2/neu-positive
      cells and provide its penetration into the target cells, as HER2/neu is a ligand
      internalizing receptor. This expression vector has potential applications to both
      gene and antibody therapies of cancer.

PMID- 16300909
TI  - Molecular and serological detection of A. centrale- and A. marginale-infected
      cattle grazing within an endemic area.
AB  - A reverse line blot hybridization (RLB) one-stage nested PCR (nPCR) for Anaplasma
      centrale and a nested PCR for Anaplasma marginale were used to detect infected
      cattle grazing within an endemic region in Israel. A novel set of PCR primers and
      oligonucleotide probes based on a 16S ribosomal RNA gene was designed for RLB
      detection of both Anaplasma species, and the performance of the molecular assays
      compared. The immunofluorescent antibody test (IFA) was used to detect antibodies
      to both Anaplasma species, whereas, a highly sensitive and specific competitive
      enzyme-linked immunosorbent assay (cELISA) was used to detect antibodies in A.
      centrale-vaccinated cattle. The RLB and the nested PCR procedures showed
      bacteremia with sensitivity of 50 infected erythrocytes per milliliter. Up to 93%
      of the A. centrale vaccinates carried specific antibodies that were detected by
      cELISA, and up to 71% of the vaccinated cattle were found to be naturally
      infected with A. marginale according to the PCR and the RLB assays. Nevertheless,
      no severe outbreaks of A. marginale infection occurred among vaccinated herds in
      this endemic region. It appears that both, molecular tools and serology are
      useful for evaluation of the vaccine efficacy. In the light of wide natural field
      infection with A. marginale, strong recommendations to continue the A. centrale
      vaccination program regime will continue until a new generation of non-blood
      based vaccine will be developed.

PMID- 16300910
TI  - IS900-PCR-based detection and characterization of Mycobacterium avium subsp.
      paratuberculosis from buffy coat of cattle and sheep.
AB  - Johne's disease is one of the main causes of economic losses in ruminants and a
      major health hazard in the developing and developed world. Up till now, many
      microbiological, serological and molecular methods have been tried for the
      detection of Mycobacterium avium subsp. paratuberculosis (MAP). In this study, we
      attempt a PCR-based detection of IS900, distinct insertion sequences of MAP from
      the buffy coat of cattle (n=262) and sheep (n=78), and direct genotyping by
      single strand conformational polymorphism (SSCP). A total of 30 (11.45%) cattle
      and one sheep (1.28%) were positive for MAP-IS900. This IS900-based PCR detection
      proved highly specific, particularly when tested on other non-MAP strains. SSCP
      analysis grouped the MAP-IS900 into four distinct clusters based on different
      band patterns. Nucleotide sequence variability between MAPs detected from sheep
      (GenBank accession ) and cattle (GenBank accession -) was noticed in the study.
      Although, in recent years IS900-PCR-based detection of MAP from WBCs is being
      used in human, its use in animals is still limited. Our work not only supports
      its use in animals but also suggests further IS900-SSCP-based MAP-genotyping,
      coupled with DNA sequencing, as a promising tool for rapid and effective Johne's
      disease surveillance.

PMID- 16300911
TI  - PCR detection of virulence-associated genes in Campylobacter jejuni strains with
      differential ability to invade Caco-2 cells and to colonize the chick gut.
AB  - In this study, the presence of 20 putative virulence genes was examined in 11
      Campylobacter jejuni isolates with different colonization and invasion abilities
      as determined in a chick colonization model and on Caco-2 cells, respectively.
      The majority of the genes were detected in all strains. Among them, there were
      genes of the flagellar secretion apparatus like flhA, flhB, flgB, flgE2, the
      flagellin genes flaA and flaB, invasion-associated genes like ciaB and iamA, the
      cytotoxin genes cdtA-C, the adhesion related gene cadF, and some genes involved
      in the colonization process (docA, docB). The plasmid gene virB11 could not be
      detected in any strain. Specific differences between the isolates were observed
      only in genes cgtB and wlaN involved in lipo-oligosaccharide (LOS) biosynthesis.
      The gene cgtB was only detectable in three of five strains with strong
      colonization and invasion abilities. Probably, wlaN can overcome the lack of cgtB
      in the two cgtB- isolates.

PMID- 16300912
TI  - Decrease of genital organ weights and plasma testosterone levels in rats
      following oral administration of leuprolide microemulsion.
AB  - Studies were conducted to develop oral leuprolide microemulsions using oleic acid
      as an absorption enhancer and to evaluate its absorption and pharmacological
      responses in rats. Oral administration of leuprolide microemulsion at a dose of 3
      mg/kg showed a greater in vivo exposure level (C(max) and AUC) than its saline
      solution. When male rats were orally given a microemulsion formulation of
      leuprolide acetate at 0.25, 0.5, and 1mg/day for 14 consecutive days, a
      significant decrease in testis, prostate and seminal vesicle weights was
      observed. In a 35-day study, the reduction of the male genital organ weights by
      once a day treatment (2 mg/rat, qd) was similar to that by twice a day treatment
      (1 mg/rat, bid) at the same dose level. From both 14- and 35-day studies, plasma
      testosterone levels were sharply increased at the beginning of the treatment, and
      then significantly decreased to below normal control level which was also
      maintained during the treatment. In female rats, similar reduction of uterus and
      ovary weights was obtained following oral administration of leuprolide
      microemulsion for 35 days. These antagonistic activities from oral leuprolide
      microemulsion were similar to a single subcutaneous injection of Lupron depot
      (3.75 mg/rat), a commercial leuprolide product. The results indicated that
      leuprolide absorbed into systemic blood circulation from the oral microemulsion
      containing oleic acid reached the plasma level which can exert its
      pharmacological effects. Increasing oral absorption of leuprolide observed in
      this study could be mediated by improved membrane permeation from oleic acid and
      reduced enzymatic degradation from microemulsions. These findings suggest that
      systemic absorption of highly water-soluble protein or peptide drugs could be
      enhanced by oral microemulsions containing oleic acid.

PMID- 16300913
TI  - Design and physicochemical characterisation of a bioadhesive patch for dose
      controlled topical delivery of imiquimod.
AB  - Clinical use of the imidazoquinoline immunomodulator imiquimod for the topical
      treatment of dysplastic and neoplastic lesions has increased markedly in recent
      years. However, despite guidance from the manufacturer of the proprietary
      imiquimod cream, there seems to be little consensus between clinicians as to the
      topically applied dose. Given that patients often apply the cream themselves at
      home, further dosing variability is expected and, consequently, accurate
      comparison of the results of different published studies is difficult. This paper
      describes, for the first time, the formulation and physicochemical
      characterisation of a bioadhesive patch for dose-controlled topical delivery of
      imiquimod as well as a new HPLC method for sensitive fluorescence determination
      of imiquimod released from such systems. Patches containing imiquimod loadings of
      4.75, 9.50 and 12.50 mg cm(-2) all released significantly more drug across a
      model membrane than the proprietary cream over a period of 6h. Inclusion of
      imiquimod in patches did not adversely affect their physicochemical properties.
      Of major importance, patches contained defined drug loadings per unit area;
      therefore, their use could reduce inter-clinician variability. This would make
      critical comparison of clinical studies and determination of an appropriate
      imiquimod dose for successful treatment much simpler. Since bioadhesive
      formulations are capable of adhering to body tissues in moist environments, the
      use of a bioadhesive patch system may allow extension of the clinical uses of
      imiquimod to the treatment of neoplastic conditions of the oral cavity and
      cervix, as well as the vulva.

PMID- 16300914
TI  - Thiolated chitosan microparticles: a vehicle for nasal peptide drug delivery.
AB  - The goal of this study was to develop a microparticulate delivery system based on
      a thiolated chitosan conjugate for the nasal application of peptides. Insulin was
      used as model peptide. For thiolation of chitosan 2-iminothiolane was covalently
      linked to chitosan. The resulting chitosan-TBA (chitosan-4-thiobutylamidine)
      conjugate featured 304.89+/-63.45 micromol thiol groups per gram polymer. 6.5% of
      these thiol groups were oxidised. A mixture of the chitosan-TBA conjugate,
      insulin and the permeation mediator reduced glutathione were formulated to
      microparticles. Control microparticles comprised unmodified chitosan and insulin.
      As second control served mannitol-insulin microparticles. All microparticulate
      systems were prepared via the emulsification solvent evaporation technique. In
      100 mM phosphate buffer pH 6.8 chitosan-TBA-insulin microparticles swelled 4.39+/
      0.52-fold in size, whereas chitosan based microparticles did not swell at all.
      Chitosan-TBA microparticles showed a controlled release of fluorescein
      isothiocyanate (FITC)-labelled insulin over 6 h. Nasal administered chitosan-TBA
      insulin microparticles led to an absolute bioavailability of 7.24+/-0.76%
      (means+/-S.D.; n=3) in conscious rats. In contrast, chitosan-insulin
      microparticles and mannitol-insulin microparticles exhibited an absolute
      bioavailability of 2.04+/-1.33% and 1.04+/-0.27%, respectively (means+/-S.D.;
      n=4). Because of these results microparticles comprising chitosan-TBA and reduced
      glutathione seem to represent a useful formulation for the nasal administration
      of peptides.

PMID- 16300915
TI  - The preparation of silybin-phospholipid complex and the study on its
      pharmacokinetics in rats.
AB  - The aim of the present study was to find a way of prepare silybin-phospholipid
      complex to make oral bioavailability of silybin increase and to study its
      physicochemical properties and to compare the pharmacokinetic characteristics and
      bioavailability after oral administration of silybin-phospholipid complex and
      silybin-N-methylglucamine in rats. Using ethanol as a reaction medium, silybin
      and phospholipids were resolved into the medium, after the organic solvent was
      removed under vacuum condition, silybin-phospholipid complex was formed. The new
      complex's physicochemical properties including scanning electron microscopy
      (SEM), transmission electron microscopy (TEM), differential scanning calorimetry
      (DSC), solubility, dissolution, etc., were tested. The concentrations of silybin
      after oral administration of silybin-phospholipid complex and silybin-N
      methylglucamine at different time in rats were determined by RP-HPLC. The
      pharmacokinetic parameters were computed by software program 3p97. Our data
      showed that silybin and phospholipids in the silybin-phospholipid complex were
      combined by non-covalent-bond, not forming a new compound and the solubility of
      silybin-phospholipid complex in water and in n-octanol was effectively enhanced.
      We found that mean plasma concentration-time curve of silybin after oral
      administration of silybin-phospholipid complex and silybin-N-methylglucamine in
      rats was both in accordance with open single-compartment model with first-order
      absorption. Pharmacokinetic parameters of silybin in rats were Tmax 10 and 5 min;
      Cmax 126.72 and 104.29 ng ml(-1); AUC(0-infinity) 1020.33 and 235.81 ng ml(-1)h,
      respectively. The bioavailability of silybin in rats was increased remarkably
      after oral administration of silybin-phospholipid complex comparing to silybin-N
      methylglucamine. This was mainly due to an impressive improvement of the
      lipophilic property of silybin-phospholipid complex and improvement of the
      biological effect of silybin.

PMID- 16300916
TI  - Virological analysis in the diagnosis of sudden children death: a medico-legal
      approach.
AB  - Infections are considered to be an important cause of unexpected death in
      children. It has also been assumed that respiratory viruses are involved in the
      genesis of sudden infant death syndrome (SIDS). The Spanish National Institute of
      Toxicology and Forensic Sciences act as the forensic reference centre for Spain.
      We analyse the experience of this centre in the virological study of 64 cases of
      sudden children death where viral serology, virological cultures, herpesviruses
      polymerase chain reaction (PCR) and electron microscopy were performed. According
      to pathological findings, death could only be attributed to an adenovirus
      infection in one amygdalitis with upper airways stenosis and asphyxia. Human
      herpes virus 6 (HHV-6) was detected by PCR in one case with pathological findings
      characteristic of SIDS. Recent infection by respiratory syncytial virus (RSV),
      Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were also detected. Meanwhile,
      85.9% of the cases yielded negative viral results. Twenty-eight infants were
      finally categorised as SIDS. Pathological findings of infection were detected in
      12 patients despite the negativity of viral analyses. Although viral infection is
      an uncommon cause of sudden children death, a complete microbiological
      investigation will help to solve the puzzle of SIDS. Definitive guidelines for
      microbiological analyses need to be updated whilst new pathogens are discovered
      or new techniques are implemented in order to clarify unsolved cases.

PMID- 16300917
TI  - HPLC-DAD determination of opioids, cocaine and their metabolites in plasma.
AB  - High performance liquid chromatography with diode array detection (HPLC-DAD) was
      used to develop a method for the simultaneous determination of morphine, codeine,
      6-acetylmorphine (6AM), cocaine, benzoylecgonine (BEG), cocaethylene, methadone
      and its metabolite, 2-ethylidene-1,5-dimethyldiphenylpyrrolidine (EDDP), in
      plasma. Following solid-phase extraction with Bond Elut Certify cartridges,
      chromatography was performed on an X-Terra RP8 column (250 mm x 4.6 mm i.d., 5
      microm particle size), using acetonitrile-phosphate buffer pH 6.53 as mobile
      phase and elution in the gradient mode. The detector response was linear at
      concentrations over the range 0.1-10 microg/mL in plasma, and the correlation
      coefficients for the eight drugs studied were all higher than 0.99. The average
      extraction recoveries from plasma ranged from 60% for BEG to 95% for methadone.
      The precision was acceptable, with coefficients of variation oscillating between
      2.55% and 6.45%. The accuracy was found to be within satisfactory limits (+/-
      8.1%). Finally, the method was applied to 21 plasma samples from fatal overdoses,
      obtaining positive results for two or more drugs.

PMID- 16300918
TI  - Catechin derivatives in Jatropha macrantha stems: characterisation and
      LC/ESI/MS/MS quali-quantitative analysis.
AB  - A phytochemical investigation on methanol extract of stems of Jatropha macrantha
      led to the isolation of catechin, catechin-7-O-beta-glucopyranoside and
      proanthocyanidin B-3 along with other catechin polymers. Their structures were
      established by NMR and ESI/MS experiments. Additionally, an LC/ESI/MS qualitative
      study and an LC/ESI/MS/MS quantitative study of the phenolic fraction of J.
      macrantha stems were performed. Combination of high performance liquid
      chromatography (HPLC) (DAD) with positive electrospray ionisation (ESI) and
      tandem mass spectrometry (MS/MS) performed with Ion Trap analyser permitted to
      have qualitative data on catechin derivatives: several other proanthocyanidins
      were detected. A mixture of proanthocyanidin polymers was characterised by direct
      introduction ESI-MS analysis. An LC/ESI/MS/MS method was developed and validated
      for separation and quantification of catechin, catechin-7-O-beta-glucopyranoside
      and proanthocyanidin B-3. Due to the sensitivity and the repeatability of the
      assay, we suggest this method as suitable for industrial quality control of raw
      materials and final products. Quantitative analyses results confirmed that
      compounds 1-3 are major compounds of the plant and, in particular,
      proanthocyanidin B-3 appears to be the most abundant.

PMID- 16300919
TI  - Color measurement of a solid active pharmaceutical ingredient as an aid to
      identifying key process parameters.
AB  - The color of a powdered active pharmaceutical ingredient (API) in an
      investigational drug was found to be the result of a number of process
      parameters. Color measurements of the solid material were derived from
      reflectance data obtained from a sphere spectrophotometer. These data provided a
      convenient and non-destructive way to track the effects of variations to the
      process parameters on the resulting material. Visual evaluation could not provide
      an objective, quantitative assessment of the material. Color of solution (COS)
      measurements did not provide adequate sensitivity to distinguish some of the
      samples from each other, even when visual differences were apparent.

PMID- 16300920
TI  - Comparison of the ability of the three endogenous GnRHs to stimulate release of
      follicle-stimulating hormone and luteinizing hormone in chickens.
AB  - It is well established that GnRH can stimulate the release of LH and FSH in
      mammals. Two GnRHs have been found in the chicken hypothalamus, cGnRH-I and -II.
      There is controversy as to whether either peptide can stimulate release of FSH in
      birds. The present studies compared the ability of cGnRH-I and -II to stimulate
      the release of FSH and LH in chickens. Lamprey (l) GnRH-III may be a specific
      releasing factor for FSH, as it selectively stimulates FSH release in rodents and
      cattle, and has been detected in the hypothalamus of rodents, sparrows and
      chickens. Therefore, the ability of lGnRH-III to stimulate LH and FSH release was
      also examined. In our first experiment, the effects of cGnRH-I and -II were
      studied using 17-week prepubertal females. Intravenous injection of cGnRH-II at 1
      and 10 microg/kg BW significantly increased LH secretion more than did cGnRH-I.
      Neither peptide significantly increased plasma FSH levels. In our second study,
      we administered cGnRH-I, -II or lGnRH-III to mature males maintained on a short
      photoperiod. cGnRH-II was again more potent than cGnRH-I in stimulating LH
      release, while lGnRH-III produced a modest LH rise. No GnRH peptide provided
      specific or potent stimulus to FSH secretion, although the high dose of cGnRH-II
      modestly enhanced FSH levels in the adult male (P < 0.05). Our results are not
      consistent with the view that lGnRH-III is a specific FSH-releasing hormone
      across multiple classes of vertebrates. We conclude that the mechanism by which
      independent release of FSH occurs in chickens remains unresolved.

PMID- 16300921
TI  - The role of axillary lymph node dissection in breast cancer patients with
      sentinel lymph node micrometastases.
AB  - AIM: To identify by means of clinical and histopathological features a subset of
      breast cancer patients with sentinel lymph-node (sN) micrometastases and
      metastatic disease confined only to the sN in order to spare them an unnecessary
      axillary lymph node dissection (ALND). MATERIALS AND METHODS: From January 1998
      to December 2004, 116 patients with sN micrometastases underwent standard ALND
      for early-stage (T1-2 N0 M0) invasive breast cancer; clinical and histopathologic
      parameters were prospectively collected and evaluated by means of univariate and
      logistic regression analysis in order to identify which patients with sN
      micrometastases were free of metastasis in axillary non-sN. RESULTS: Sixteen of
      116 patients with sN micrometastases had tumour involvement of non-sN, with six
      and 10 patients having non-sN micrometastases and macrometastases, respectively.
      None of 19 patients with primary tumour measuring </= 10 mm had tumour-positive
      non-sN; moreover, none of 15 patients with G1 tumours had non-sN metastases. The
      mean tumour size in patients with non-sN involvement was 21.3 mm (range, 12-40
      mm). Univariate test of association between clinical and histopathologic features
      and non-sN status showed that the primary tumour size (P=0.005) and the presence
      of lymphovascular invasion (P=0.000) were the only significant predictors of non
      sN involvement. By logistic regression, primary tumour size (P=0.011),
      lymphovascular invasion (P=0.001), and size of sN micrometastases were the only
      variables remaining into the model, although the latter parameter was not
      statistically significant. CONCLUSIONS: In patients with sN micrometastases,
      primary tumour size and lymphovascular invasion significantly predict non-sN
      status; notably, no patient with T1a-T1b and/or G1 tumours had non-sN metastases
      so that they could be spared an unnecessary ALND.

PMID- 16300922
TI  - Identification of novel pathway regulation during myogenic differentiation.
AB  - Stem cell differentiation is governed by extracellular signals that activate
      intracellular networks (or pathways) to drive phenotypic specification. Using a
      novel gene clustering strategy we determined pathway relationships from a genome
      wide transcriptional dataset of skeletal myoblast differentiation. Established
      myogenic pathways, including cell contractility and cell-cycle arrest, were
      predicted with extreme statistical significance (p approximately 0). In addition,
      gene sets associated with angiogenesis, neuronal activity, and mRNA splicing were
      regulated, exposing developmental and therapeutic implications. Acquisition of
      transcriptional data spanning the entire differentiation time course provided
      context for a dynamic landscape of functional pathway regulation. This novel
      perspective on myogenic cell differentiation revealed previously unrecognized
      patterns of regulation. We predict that similar analyses will facilitate ongoing
      efforts to define molecular mechanisms in other stem cell and developmental
      paradigms. Finally, by combining an iterative process of analysis with
      supplementation of novel pathways, this application may evolve into a powerful
      discovery tool.

PMID- 16300923
TI  - Identification of pathogenic Helicobacter species by chaperonin-60
      differentiation on plastic DNA arrays.
AB  - A microarray method for bacterial species identification based on cpn60 and 16S
      rDNA hybridization was developed. Specific cpn60 or 16S rDNA oligonucleotides
      from various Helicobacter or Campylobacter species were printed and immobilized
      onto a proprietary plastic solid support. Using universal primers, fragments
      derived from either cpn60 or 16S rDNA genes from single isolates or from a
      complex human waste sludge DNA sample spiked with Helicobacter pylori were
      biotinylated and hybridized to the plastic slide. Subsequent querying with a
      streptavidin-horseradish peroxidase conjugate followed by color development using
      tetramethylbenzidine resulted in accurate Helicobacter species identification
      with no cross-hybridization to either the 16S rDNA or the cpn60 sequence of a
      closely related strain of Campylobacter jejuni. The combination of a
      nonfluorescence visual detection system with a polymer-based DNA microarray slide
      has resulted in a molecular tool that should prove useful in numerous
      applications requiring rapid, low-cost bacterial species identification.

PMID- 16300924
TI  - Human mitochondrial pyrophosphatase: cDNA cloning and analysis of the gene in
      patients with mtDNA depletion syndromes.
AB  - Pyrophosphatases (PPases) catalyze the hydrolysis of inorganic pyrophosphate
      generated in several cellular enzymatic reactions. A novel human pyrophosphatase
      cDNA encoding a 334-amino-acid protein approximately 60% identical to the
      previously identified human cytosolic PPase was cloned and characterized. The
      novel enzyme, named PPase-2, was enzymatically active and catalyzed hydrolysis of
      pyrophosphate at a rate similar to that of the previously identified PPase-1. A
      functional mitochondrial import signal sequence was identified in the N-terminus
      of PPase-2, which targeted the enzyme to the mitochondrial matrix. The human
      pyrophosphatase 2 gene (PPase-2) was mapped to chromosome 4q25 and the 1.4-kb
      mRNA was ubiquitously expressed in human tissues, with highest levels in muscle,
      liver, and kidney. The yeast homologue of the mitochondrial PPase-2 is required
      for mitochondrial DNA maintenance and yeast cells lacking the enzyme exhibit
      mitochondrial DNA depletion. We sequenced the PPA2 gene in 13 patients with
      mitochondrial DNA depletion syndromes (MDS) of unknown cause to determine if
      mutations in the PPA2 gene of these patients were associated with this disease.
      No pathogenic mutations were identified in the PPA2 gene of these patients and we
      found no evidence that PPA2 gene mutations are a common cause of MDS in humans.

PMID- 16300925
TI  - Visualization and quantification of the medial surface dynamics of an excised
      human vocal fold during phonation.
AB  - SUMMARY: The purpose of this investigation was to investigate physical mechanisms
      of vocal fold vibration during normal phonation through quantification of the
      medial surface dynamics of the fold. An excised hemilarynx setup was used. The
      dynamics of 30 microsutures mounted on the medial surface of a human vocal fold
      were analyzed across 18 phonatory conditions. The vibrations were recorded with a
      digital high-speed camera at a frequency of 4,000 Hz. The positions of the
      sutures were extracted and converted to three-dimensional coordinates using a
      linear approximation technique. The data were reduced to principal eigenfuctions,
      which captured over 90% of the variance of the data, and suggested mechanisms of
      sustained vocal fold oscillation. The vibrations were imaged as the following
      phonatory conditions were manipulated: glottal airflow, an adductory force
      applied to the muscular process, and an elongation force applied to the thyroid
      cartilage. Over the range of variables studied, only the variation in glottal
      airflow yielded significant changes in subglottal pressure and fundamental
      frequency. All recordings showed high correlation for the distribution of the
      dynamics across the medial surface of the vocal fold. The distribution of the
      different displacement directions and velocities showed the highest variations
      around the superior region of the medial surface. Although the computed vibration
      patterns of the two largest empirical eigenfunctions were consistent with
      previous experimental observations, the relative prominence of the two
      eigenfunctions changed as a function of glottal airflow, impacting theories of
      vocal efficiency and vocal economy.

PMID- 16300926
TI  - Physiological studies of retrusive movements of the human tongue.
AB  - SUMMARY: This study identified that physiologically the superior pharyngeal
      constrictor muscle at the level of the base of the tongue contributes to
      retrusive movement of the tongue with constriction of the mid-pharyngeal cavity
      and possesses unique properties in terms of motor speech control along with the
      genioglossus muscle. From a kinematic study involving trans-nasal fiberscopy and
      lateral X-ray fluorography, retrusive movement of the tongue was highly
      correlated with constrictive movement of the mid-pharyngeal cavity. An
      electromyographic study revealed that the superior pharyngeal constrictor muscle
      at the level of the base of the tongue contributes to retrusive movement of the
      tongue and that the genioglossus muscle contributes to protrusive movement. We
      also noted that this relationship between the activities of these two muscles
      were in response to postural changes during vowel productions without changes in
      the acoustic features. These findings suggest that these two muscles act not only
      antagonistically to produce retrusive and protrusive movement of the tongue, but
      also they complement each other to conserve the shape of the vocal tract for
      speech production. The functional relationship between these two muscles could
      contribute the consecutive movement of human speech production under various
      conditions and might be useful when applying rehabilitation approaches for the
      patients with neurological speech and swallowing disorders.

PMID- 16300927
TI  - A neural network model for coordination of hand gesture during reach to grasp.
AB  - In this paper a neural network model for spatio-temporal coordination of hand
      gesture during prehension is proposed. The model includes a simplified control
      strategy for whole hand shaping during grasping tasks, that provides a realistic
      coordination among fingers. This strategy uses the increasing evidence that
      supports the view of a synergistic control of whole fingers during prehension. In
      this control scheme, only two parameters are needed to define the evolution of
      hand shape during the task performance. The proposal involves the design and
      development of a Library of Hand Gestures consisting of motor primitives for
      finger pre-shaping of an anthropomorphic dextrous hand. Through computer
      simulations, we show how neural dynamics of the model leads to simulated grasping
      movements with human-like kinematic features. The model can provide clear-cut
      predictions for experimental evaluation at both the behavioural and neural levels
      as well as a neural control system for a dextrous robotic hand.

PMID- 16300928
TI  - Constructing a speculative kernel machine for pattern classification.
AB  - We propose and investigate the performance of a new geometry-based algorithm
      designed to identify potentially informative data points for classification. An
      incremental QR update scheme is used to build a classifier using a subset of
      these points as radial basis function centers. The minimum descriptive length and
      the leave-one-out error criteria are employed for automatic model selection. The
      proposed scheme is shown to generate parsimonious models, which perform
      generalization comparable to the state-of-the-art support and relevance vector
      machines.

PMID- 16300929
TI  - Caspases 3 and 9 are translocated to the cytoskeleton and activated by thrombin
      in human platelets. Evidence for the involvement of PKC and the actin filament
      polymerization.
AB  - Platelets express, among others, initiator caspase 9 and effector caspase 3. Upon
      activation by physiological agonists, calcium ionophores or under shear stress
      they might develop apoptotic events. Although it is well known that the
      cytoskeletal network plays a crucial role in apoptosis, the relationship between
      caspases 3 and 9 and the cytoskeleton is poorly understood. Here we demonstrate
      that the physiological agonist thrombin is able to induce activation of caspases
      3 and 9 in human platelets and significantly increases the amount in the
      cytoskeleton of the active forms of both caspases and the procaspases 3 and 9.
      After stimulation with thrombin the amount of active caspases 3 and 9 in the
      cytosolic and cytoskeletal fractions were significantly reduced in Ro-31-8220
      treated cells, which demonstrates that caspases activation and association with
      the cytoskeleton needs the contribution of PKC. Inhibition of actin
      polymerization by cytochalasin D inhibits translocation and activation of both
      caspases, suggesting that thrombin stimulates caspase 3 and 9 activation and
      association with the reorganizing actin cytoskeleton. Finally, our results show
      that inhibition of thrombin-induced caspase activation has no effect on their
      translocation to the cytoskeleton although impairment of thrombin-evoked caspase
      translocation has negative effects on caspase activity, suggesting that
      translocation to the cytoskeleton might be important for caspase activation by
      thrombin in human platelets.

PMID- 16300930
TI  - Heightened stimulus salience renders deluded schizophrenics less susceptible to
      the 'famous names illusion'.

PMID- 16300931
TI  - Infant motor development and adult cognitive functions in schizophrenia.
AB  - BACKGROUND: Childhood neuromotor dysfunction is a risk factor for schizophrenia,
      a disorder in which cognitive deficits are prominent. The relationship between
      early neurodevelopment and adult cognition in schizophrenia remains unclear.
      METHODS: We examined the associations between infant motor development and adult
      cognitive functions in schizophrenia (n = 61) and the general population (n =
      104) in a sample drawn from the The Northern Finland 1966 Birth Cohort. Data on
      ages of learning to stand and walk with or without support were obtained at age
      12 months by health visitor assessment. Neurocognitive measures at age 33-35
      included executive function, verbal and visual episodic memory, and visuo-spatial
      working memory. RESULTS: The schizophrenia group achieved neuromotor milestones
      later and performed significantly worse than the control group on all measures of
      cognition. In pooled analyses there were associations between infant motor
      development and adult cognition in the domains of executive function, verbal
      learning and visuospatial working memory, but not in visual object learning. The
      pattern of associations between development and cognition was similar in
      schizophrenia and the general population. CONCLUSIONS: These findings are
      consistent with the hypothesis that in schizophrenia mild infant motor
      developmental delay and adult cognitive deficits (at least in some domains) are
      age dependent manifestations of the same underlying neural process. Thus, they
      may be better considered as part of a single longitudinal syndrome.

PMID- 16300932
TI  - Optimization and validation of a colorimetric assay for Tetrahymena sp. survival.
AB  - A colorimetric assay based on the reduction of 3-(4,5-dimethyl-2-thiazol-2-yl)
      2,5-diphenyl-2h-tetrazolium bromide (MTT), for the quantification of Tetrahymena
      sp. survival is described. An increase in the concentration of Tetrahymena sp.
      cells from 0 to 1 x 10(6) cells/ml produced a linear (R(2)=0.9965) increase in
      the optical density (OD, 570-630 nm), and dead cells (pre-exposed to 250 mg/l
      formalin for 4 h) did not produce a background reading. Cells exposed to
      sublethal concentrations to formalin (100 mg/l or less for 4 h) recovered their
      growth. Using the MTT assay, we determined that Tetrahymena sp. is sensitive to
      formalin, chloramine-T, hydrogen peroxide, copper sulfate and NaCl. The
      sensitivity increased with increasing chemical concentrations and exposure time.
      Tetrahymena sp. was resistant to bromex and malachite green. The use of this
      assay in drug screening for the development of treatments for tetrahymenosis and
      as a bioassay to evaluate the toxicity of environmental toxicants is discussed.

PMID- 16300933
TI  - Testing of a whole genome PCR scanning approach to identify genomic variability
      in four different species of lactic acid bacteria.
AB  - Genomes can be markedly heterogeneous in conspecific bacterial strains. Genome
      sequences can be used to analyze genome plasticity via a PCR(2) (plasticity of
      chromosome revealed by PCR) approach. Small-sized chromosomes can indeed be fully
      amplified by long-range PCR with a set of primers designed using a reference
      strain and then applied to several other strains. Analysis of the resulting
      patterns can reveal genome plasticity. GenoFrag, a software package for the
      design of primers optimized for PCR(2) [N. Ben Zakour, M. Gautier, R. Andonov, D.
      Lavenier, M.F. Cochet, P. Veber, A. Sorokin, Y. Le Loir, GenoFrag: Software to
      design primers optimized for whole genome scanning by long-range PCR
      amplification, Nucleic Acids Res. 32 (2004) 17-24] was developed for the analysis
      of bacterial genome plasticity by whole genome amplification in approximately 10
      kb-long fragments. By applying GenoFrag, we provide herewith evidence that genome
      plasticity can be analyzed in lactic acid bacteria using a PCR(2) approach. The
      genome sequences of Lactococcus lactis IL1403, Lactobacillus plantarum WCFS1,
      Lactobacillus bulgaricus ATCC11842 and Bifidobacterium longum NCC2705 were used
      to design four sets of primers. Each set was evaluated in silico to check that it
      ensured optimum coverage of the bacterial chromosome. To validate the primers
      generated by GenoFrag, a subset of primers was successfully used in LR-PCR
      experiments on genomic DNA from four L. bulgaricus strains.

PMID- 16300934
TI  - Potential application of poly(N-isopropylacrylamide) gel containing polymeric
      micelles to drug delivery systems.
AB  - We have investigated rapidly thermo-responsive NIPA gel containing polymer
      surfactant PMDP (NIPA-PMDP gel) as a potential drug carrier using (+)-l-ascorbic
      acid as a model drug. In the NIPA-PMDP gel system micelles of polymer surfactant
      PMDP are trapped by the entanglement of polymer chains inside the gel networks.
      Therefore, in principle the gel system tightly stores targeted drug in the
      micelles and rapidly releases controlled amount of the drug by switching on-off
      of external stimuli such as temperature or infrared laser beam. In our
      investigation on release profile, the NIPA-PMDP gel system showed completely
      different releasing behavior from that of the conventional NIPA gel. The NIPA
      PMDP gel released rapidly all loaded (+)-l-ascorbic acid above the phase
      transition temperature (ca. 34 degrees C), while slowly released the
      corresponding amount of the drug below the temperature. In contrast, the
      conventional NIPA gel released more slowly limited amount of the drug above the
      phase transition temperature while similarly did to the NIPA-PMDP gel below the
      temperature. The release profile of the NIPA-PMDP gel seems to be governed by
      only kinetics of volume phase transition of the gel network but not by the
      hydrophobic domains of the micelles probably because of too hydrophilic nature of
      (+)-l-ascorbic acid.

PMID- 16300935
TI  - [Morbidity and mortality in a pediatric hospital at Dakar].

PMID- 16300936
TI  - [Breast feeding: health benefits for child and mother].
AB  - Breast milk contains hormones, growth factors, cytokines, cells, etc., and offers
      many advantages over cow's milk or soy protein infant formulae. The composition
      of breast milk is influenced by gestational and postnatal age. Prevalence of
      breastfeeding in France is one of the lowest in Europe: in 2003, only 58% of
      infants were breastfed when leaving the maternity ward, for a median duration of
      10 weeks. Breastfeeding allows normal growth until at least 6 months of age, and
      can be prolonged until the age of 2 years or more, provided that complementary
      feeding is started after 6 months. Breastfeeding is associated with slightly
      enhanced performance on tests of cognitive development. Exclusive breastfeeding
      for at least 3 months is associated with a lower incidence and severity of
      diarrhoea, otitis media and respiratory infection. Exclusive breastfeeding for at
      least 6 months is associated with a lower incidence of allergic disease in at
      risk infants (infants with at least one first-degree relative presenting with
      allergy). Breastfeeding is also associated with a lower incidence of obesity
      during childhood and adolescence, as well as with a lower incidence of
      hypertension and hypercholesterolemia in adulthood. Maternal infection with
      hepatitis B and C virus is not a contraindication to breastfeeding, as opposed to
      HIV infection and galactosemia. A supplementation with vitamin D and K is
      necessary in the breastfed infant. Very few medications contraindicate
      breastfeeding. Premature babies can be breastfed and/or receive mother's milk
      and/or bank milk, provided they receive energy, protein and mineral supplements.
      Return to prepregnancy weight is earlier in breastfeeding mothers. Breastfeeding
      is also associated with a decreased risk of breast and ovarian cancer in the
      premenopausal period, and of hip fractures and osteoporosis in the postmenopausal
      period.

PMID- 16300937
TI  - [Adoption: ethical bases of an awaited amendment].

PMID- 16300938
TI  - Tandem Sp1/Sp3 sites together with an Ets-1 site cooperate to mediate alpha11
      integrin chain expression in mesenchymal cells.
AB  - Alpha11beta1 integrin is a collagen receptor, which is expressed in a highly
      regulated manner in a specific subset of ectomesenchymally and mesodermally
      derived cells. We previously established that a 3 kb region upstream of the
      transcription start site of the ITGA11 gene efficiently induced alpha11
      transcription in a cell-type specific manner. Using the human fibrosarcoma cell
      line HT1080 and human skin fibroblasts, we now report that the majority of the
      activity in the proximal promoter resides in a region spanning nt +25 to nt -176.
      Mutation and deletion analyses using luciferase reporter assays showed that
      tandem low affinity Sp1/Sp3 binding sites, together with an Ets-1-like binding
      site, were needed for the proximal promoter activity in mesenchymal cells. EMSAs
      and supershift assays showed that Sp1 and Sp3 both bind to the Sp1/Sp3 binding
      sites, whereas occupation of the Ets-1 binding site appears to be Sp3-dependent.
      Chromatin immunoprecipitation assays verified that Sp1, Sp3 and Ets-1 can bind
      the promoter in vivo. In heterologous Drosophila SL2 cells, Sp1, Sp3 and Ets-1
      all transactivated the alpha11 promoter, with Sp1 being the most efficient
      activator. The lack of any synergistic effect of Sp1/Sp3 and Ets-1 in SL2 cells
      indicates that an Ets family member other than Ets-1 might be involved in
      regulating alpha11 transcription in mesenchymal cells. The central role of Sp1 in
      regulating alpha11 RNA transcription was further verified by the ability of the
      Sp1 inhibitor mithramycin A to efficiently attenuate alpha11 RNA and protein
      levels in primary fibroblasts. The proximal promoter itself was able to confer
      cell-type specific transcription on HT1080 cells and embryonic fibroblasts but
      not on U2OS and JAR cells. We speculate that the "mesenchymal signature" of
      alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3,
      fibroblast-specific combinations of Ets family members and yet unidentified
      enhancer-binding transcription factors.

PMID- 16300939
TI  - Age, sex, material deprivation and respiratory mortality.
AB  - The aim of this study was to examine the effects of age, sex and social
      deprivation on mortality rates for respiratory infection. An ecological study was
      undertaken, using official public health mortality data and population census
      data for the West Midlands health region, UK. Postcodes at the time of death were
      used to assign Townsend deprivation scores and the resulting deprivation
      quintile. Poisson regression analysis was used to estimate the association
      between respiratory mortality, deprivation quintile, age and sex. In most age
      groups there was a statistically significant trend of increasing mortality with
      increasing deprivation. The relative risk for the most deprived was highest in
      the 45-64 year age-group (RR=4.4, 95% CI 4.0, 4.8). However, the absolute risks
      were greater in those aged 75-84 years (RR=1.3, 95% CI 1.3, 1.4) where the annual
      death rate was 669 per 100,000. Consistently higher mortality rates were seen in
      males. These results suggest that the risk of mortality from respiratory
      infection varies by sex and generally increases with increasing age and
      deprivation quintile. The identified association between deprivation and
      mortality from respiratory infections is consistent with the effect of
      deprivation on many other diseases. Addressing the social determinants of ill
      health may help to reduce the high burden of respiratory mortality in the UK.
      However, individual level studies and examination of other areas are needed to
      explain the mechanisms by which deprivation increases the risk of mortality from
      respiratory infection, and thereby identify target groups for effective
      interventions.

PMID- 16300940
TI  - Probability of real-time detection versus probability of infection for
      aerosolized biowarfare agents: a model study.
AB  - Real-time biosensors are expected to provide significant help in emergency
      response management should a terrorist attack with the use of biowarfare, BW,
      agents occur. In spite of recent and spectacular progress in the field of
      biosensors, several core questions still remain unaddressed. For instance, how
      sensitive should be a sensor? To what levels of infection would the different
      sensitivity limits correspond? How the probabilities of identification correspond
      to the probabilities of infection by an agent? In this paper, an attempt was made
      to address these questions. A simple probability model was generated for the
      calculation of risks of infection of humans exposed to different doses of
      infectious agents and of the probability of their simultaneous real-time
      detection/identification by a model biosensor and its network. A model biosensor
      was defined as a single device that included an aerosol sampler and a device for
      identification by any known (or conceived) method. A network of biosensors was
      defined as a set of several single biosensors that operated in a similar way and
      dealt with the same amount of an agent. Neither the particular deployment of
      sensors within the network, nor the spacious and timely distribution of agent
      aerosols due to wind, ventilation, humidity, temperature, etc., was considered by
      the model. Three model biosensors based on PCR-, antibody/antigen-, and MS
      technique were used for simulation. A wide range of their metric parameters
      encompassing those of commercially available and laboratory biosensors, and those
      of future, theoretically conceivable devices was used for several hundred
      simulations. Based on the analysis of the obtained results, it is concluded that
      small concentrations of aerosolized agents that are still able to provide
      significant risks of infection especially for highly infectious agents (e.g. for
      small pox those risk are 1, 8, and 37 infected out of 1000 exposed, depending on
      the viability of the virus preparation) will remain undetected by the present,
      most advanced, or even future, significantly refined real-time biosensors.

PMID- 16300941
TI  - Kinetic properties of a commercial and a native inoculum for aerobic milk fat
      degradation.
AB  - The aerobic fat biodegradation potential and growth characteristics of a
      commercial and a native inoculum (activated sludge from a dairy wastewater
      treatment pond), were evaluated. Batch tests were conducted with a medium based
      on butter oil, as the sole source of carbon, and mineral salts. Residual fat,
      biomass and CO(2) production were measured. Overall fat removal values were above
      78% for both inocula. The growth kinetics of the commercial and native inocula
      followed Haldane and Monod models respectively. Both inocula showed a similar
      behaviour when butter oil concentration was under 360 mg/l; at higher values, the
      difference between the growth rates increased as a consequence of the inhibition
      exhibited by the commercial inoculum. The selection of an inoculum for
      bioaugmentation of bioreactors in the wastewater treatment requires a
      comprehensive knowledge of their degradation ability and tolerance to fluctuating
      compounds and of the operational conditions that will be utilized.

PMID- 16300942
TI  - Synthesis and reactivity with beta-lactamases of a monobactam bearing a retro
      amide side chain.
AB  - The monobactam sodium 3-benzylcarbamoyl-2-oxo-1-azetidinesulfonate, bearing a
      retro (vs classical beta-lactam)-amide side chain, has been synthesized and the
      kinetics of its reaction with typical beta-lactamases studied. The new compound
      is generally a poorer substrate than the analogous compound with a normal side
      chain but its formation of a transiently stable complex with a class C beta
      lactamase sustains the retro-amide side-chain concept.

PMID- 16300943
TI  - Inhibition of DNA helicases with DNA-competitive inhibitors.
AB  - Helicases form an attractive protein family for drug discovery because they are
      involved in various human diseases. In this report, we show that it is possible
      to inhibit both the ATPase and the helicase activities of a DNA helicase with
      dibenzothiepins that bind at its nucleic acid binding site. These results suggest
      a drug discovery strategy to inhibit DNA helicases.

PMID- 16300944
TI  - Design, synthesis, and evaluation of 2-alkoxydihydrocinnamates as PPAR agonists.
AB  - A series of 2-alkoxydihydrocinnamates were synthesized as PPARgamma and PPARalpha
      dual agonists. In vitro studies in cell model showed that these compounds were
      efficacious. Compound 1g was found to be a potent PPARalpha/gamma dual agonist
      and will be further evaluated for the treatment of type II diabetes.

PMID- 16300945
TI  - Aplysamine-1 and related analogs as histamine H3 receptor antagonists.
AB  - Aplysamine-1 (1), a marine natural product, was synthesized and screened for in
      vitro activity at the human and rat histamine H3 receptors. Aplysamine-1 (1) was
      found to possess a high binding affinity for the human H3 receptor (Ki = 30+/-4
      nM). Synthetic analogs of 1, including des-bromoaplysamine-1 (10) and dimethyl-{2
      [4-(3-piperidin-1-yl-propoxy)-phenyl]-ethyl}-amine (13), were potent H3
      antagonists.

PMID- 16300946
TI  - Design and total synthesis of a fluorescent phorboxazole A analog for cellular
      studies.
AB  - To enable studies to elucidate the intracellular processing and targeting of the
      potent cytostatic/apoptotic anticancer natural products phorboxazoles A and B, a
      fluorescent derivative has been developed. This involved the total syntheses of
      the terminal alkyne 33-O-Me-45,46-dehydrobromophorboxazole A (MDHBPA) and a
      terminal vinyl iodide derivative of the blue fluorescent dye N,N,-dimethyl-7
      aminocoumarin (DMC). Sonogashira coupling of these partners provided enyne DMC
      MDHBPA in high yield.

PMID- 16300947
TI  - Substituted 4-hydroxyphenyl sulfonamides as pathway-selective estrogen receptor
      ligands.
AB  - The transcription factor nuclear factor-kappaB (NF-kappaB) is a key component in
      the onset of inflammation. We describe here a series of 4-hydroxyphenyl
      sulfonamide estrogen receptor (ER) ligands that selectively inhibit NK-kappaB
      transcriptional activity but are devoid of conventional estrogenic activity.

PMID- 16300948
TI  - Insertion of the force applied to handles into centre of pressure calculation
      modifies the amplitude of centre of pressure shifts.
AB  - This study examined situations where handles were used as additional postural
      supports. It aimed at determining the amplitude of centre of pressure (COP)
      shifts when considering or not the vertical handles reaction force. Eight healthy
      male subjects (24+/-6 years, body mass 65+/-5kg and height 175+/-7cm) voluntarily
      took part in the experiment. Subjects had to voluntarily rock on their heels or
      rise on their toe-tips while using handles. The vertical component of the handles
      forces and ground reaction force was measured and the shifts of the COP were
      calculated while inserting or not the handles forces. Significant differences
      were observed when comparing the amplitude of COP shifts calculated with or
      without the insertion of the handles forces. This study shows that the
      measurement of the handles forces should not be omitted, for a rigorous analysis
      of postural tasks performed in conditions including additional postural supports
      like handles.

PMID- 16300949
TI  - Biomechanical implications of the negative heel rocker sole shoe: gait kinematics
      and kinetics.
AB  - Rocker sole shoes are commonly prescribed to diabetic patients with insensate
      feet. Recent passage of the therapeutic shoe bill has drawn an increased focus to
      prescription rehabilitative footwear. The purpose of this work is to investigate
      the dynamics of lower extremity joints (hip, knee and ankle) with the application
      of a negative heel rocker sole shoe under controlled lab conditions. Forty normal
      adults volunteered for gait evaluations using controlled baseline and
      prescription negative heel rocker sole shoes. Three-dimensional motion analysis
      techniques were used to acquire kinematic and kinetic data using a six-camera
      Vicon 370 motion system and two AMTI force plates. No significant change in
      walking speed or stride length was seen with the negative heel rocker shoe,
      although cadence was increased. The most significant kinematic changes with the
      application of the negative heel shoe occurred at the ankle in the sagittal plane
      with increased plantarflexion at terminal stance. Significant hip and knee
      changes were also noted with increased mid-stance hip extension and knee flexion.
      The most significant kinetic effects were seen in the transverse plane followed
      by changes in the sagittal and coronal planes. Changes in power were mostly noted
      in the sagittal plane. Other statistically significant changes in gait kinematics
      and kinetics were observed, although the magnitudes and durations were limited
      and as a result were not considered clinically significant. The study results
      indicated the negative heel rocker shoe significantly altered proximal joint
      metrics (hip and knee). The most significant distal joint alterations were seen
      in sagittal plane ankle kinetics. These kinematic and kinetic changes, along with
      previously studied effects of pressure relief at the metatarsal heads, should aid
      medical professionals in prescribing prophylactic footwear.

PMID- 16300950
TI  - Tuberculosis of patella.
AB  - Osteoarticular tuberculosis is rare and affects the knee in about 8% of cases and
      the patella in less than 0.1%. This study reports a series of five patients who
      were immunologically competent but living in an endemic area for tuberculosis.
      Treatment with antituberculous therapy and early mobilization of the knee joint
      led to a successful outcome in all cases without patellectomy or arthrodesis.

PMID- 16300951
TI  - Soft tissue allografts in the knee: a survey of UK usage and a report of a
      combined user/provider collaborative group.

PMID- 16300952
TI  - Self-aggregation of synthetic zinc chlorophyll derivative possessing a
      perfluoroalkyl group in a fluorinated solvent.
AB  - Zinc 3(1)-hydroxy-13(1)-oxo-chlorin possessing a perfluoroheptyl group on the 17
      propionate was prepared by modifying chlorophyll a. The synthetic compound self
      aggregated in 0.1% (v/v) THF and HCFC225cb (CClF2CF2CHClF) to give similar large
      oligomers to natural light-harvesting antennae of green photosynthetic bacteria
      and their models. Visible absorption, circular dichroism, and fluorescence
      emission spectra showed that F-F interaction between the perfluoroheptyl side
      chain and the fluorinated solvent (HCFC225cb) stabilized the supramolecular
      structure. The core part of the supramolecular structure was constructed by a
      special bond of Zn...O3(1)-H...O=C13(1) and pi-pi stacking, and the 17
      propionates were at the peripheral part.

PMID- 16300953
TI  - Synthesis and antibacterial activity of some new 1-heteroaryl-5-amino-3H/methyl-4
      phenylpyrazoles.
AB  - The regioselective synthesis of 1-heteroaryl-5-amino-4-phenylpyrazoles 3a-g and 1
      heteroaryl-5-amino-3-methyl-4-phenylpyrazoles 3h-n was achieved by the treatment
      of heteroarylhydrazines 1a-g with alpha-phenylformylacetonitrile 2a and alpha
      phenylacetylacetonitrile 2b, respectively. The structures of the compounds 3 were
      established by the combined use of 1H and 13C NMR spectroscopy. All the fourteen
      compounds were tested for their in vitro antibacterial activity against three
      Gram-positive and two Gram-negative bacteria. Six compounds 3a, 3d, 3e, 3g, 3l,
      and 3n from this series were found to be equipotent or more potent than the
      commercial antibiotics (Linezolid and Cefroxime axetil).

PMID- 16300954
TI  - A combined 148Gd/244Cm source for energy calibration of alpha-spectrometers.
AB  - For high-resolution alpha-particle spectroscopy, detector calibration sources of
      highest performance are required concerning thickness and homogeneity. In
      addition, the alpha-emitting radionuclides must have adequate half-lives and
      alpha-emission energies. This paper describes a new type of alpha-emitting
      calibration source, represented by a mixture of 148Gd and 244Cm. This system
      covers an alpha-energy range from 3.18 MeV (148Gd) to 5.76 and 5.80 MeV (244Cm).
      The source has been prepared by electrolytic deposition and has good performance
      in terms of thickness and homogeneity.

PMID- 16300955
TI  - A facile method for post-conjugation prosthetic radioiodination of "mini
      peptides".
AB  - Prosthetic radioiodination methods were developed to facilitate the labeling of
      proteins devoid of tyrosine(s) or when these moieties are crucial for biological
      activity. This method involves the use of the so-called Bolton-Hunter-type
      reagents. However, the in vivo instability of the label prompted the search for
      more stable groups. Although these second generation reagents have worked well
      with proteins and peptides, the current reaction scheme takes a long time to
      perform. A simplified method may be more appropriate especially from radiation
      safety point of view. More importantly, for short-lived halogens, advantage may
      be gained utilizing a shorter reaction time. Recently we reported on the
      radioiodination of interleukin-8 (IL-8) using the pyridine carboxylate-derived
      activated ester. We have successfully conjugated this prosthetic group to tri-
      and tetrapeptides harboring the somatostatin (SST) receptor recognition units and
      characterized by HPLC and MS. The radioiodination was accomplished using the
      Iodogen method in a reasonable yield (mean=60%). The total synthesis time was
      approximately 60 min, which was 3-4 times shorter than the classical two-step
      method. Preliminary biodistribution of the radiolabeled peptide showed uptake in
      some of the organs known to express SST receptors. Injection of a low specific
      activity tracer significantly decreased the retention of radioactivity in these
      organs.

PMID- 16300956
TI  - Transient striatal delivery of GDNF via encapsulated cells leads to sustained
      behavioral improvement in a bilateral model of Parkinson disease.
AB  - Numerous studies have shown the neuroprotective and regenerative benefits of
      glial cell line-derived neurotrophic factor (GDNF) in animal models of PD. Brain
      delivery of GDNF can, however, be associated with limiting side-effects in both
      primates and PD patients, rendering the duration of delivery a critical factor.
      In the present study, the effects of transient vs. sustained GDNF delivery by
      encapsulated cells were evaluated in a bilateral animal model, closely mimicking
      advanced PD. One week following bilateral striatal 6-hydroxydopamine injections
      in rats, capsules loaded with human fibroblasts genetically engineered to release
      GDNF were bilaterally implanted in the striatum. GDNF delivery resulted in a
      significant improvement of movement initiation and swimming performance in the
      lesioned animals, associated with striatal reinnervation of dopaminergic fibers.
      To test the sustainability of the behavioral improvement, GDNF-secreting capsules
      were withdrawn in a subgroup of animals, 7 weeks post-implantation. Strikingly,
      both the behavioral and morphological improvements were maintained until the
      sacrifice of the animals 6 weeks post-GDNF withdrawal. The sustained cellular and
      behavioral benefits after GDNF washout suggest the need for temporary delivery of
      the trophic factor in PD. Retrievable encapsulated cells represent an attractive
      delivery tool to achieve this purpose.

PMID- 16300957
TI  - Loss of function mutations of the GJB2 gene detected in patients with DFNB1
      associated hearing impairment.
AB  - Mutations in GJB2, which encodes the gap junction protein connexin 26 (Cx26), are
      one of the major causes for inherited and sporadic nonsyndromic hearing
      impairment. This study aimed to functionally characterize more frequent GJB2
      mutations identified in patients showing nonsyndromic hearing impairment.
      Following injection of wild type and mutated cRNA in Xenopus oocytes, Cx26
      hemichannel activity was measured by depolarization activated conductance in
      noncoupled oocytes. All mutants showed a partially or completely defective
      phenotype, except (V27I)Cx26, a polymorphism tested as positive control.
      Coexpression of wild type and mutant Cx26 injected at equimolar levels revealed
      that p.M34T, p.V37I and p.I82M, but not p.G59V, p.L90P, p.R127H and p.R143W exert
      a dominant inhibitory effect. When coexpressed with Cx30, a connexin partially
      colocalized with Cx26 in the cochlea, all mutants had a dominant behavior. This
      study provides data that might be important for the improvement of genetic
      diagnosis and counseling for patients with hearing impairment.

PMID- 16300958
TI  - The electric field induced by light can explain cellular responses to
      electromagnetic energy: a hypothesis of mechanism.
AB  - When cells are irradiated with visible and near-infrared wavelengths a variety of
      stimulatory effects are observed in their metabolism. To explain the observed
      light effects, researchers try to identify the chromophores that are involved in
      the processes. However, the mechanism of light absorption by a chromophore does
      not explain many of the experimental observations and therefore the primary
      mechanism for cellular light responses remains unproven. In addition to the
      ability of photons to produce electronic excitation in chromophores, light
      induces a wave-like alternating electric field in a medium that is able to
      interact with polar structures and produce dipole transitions. These dipole
      transitions are analyzed in the present article at different cellular and
      biochemical levels, leading to the proposal that the primary mechanism for the
      observed light effects is related to the light-induced electric field.

PMID- 16300959
TI  - The antithrombotic action of propylene glycol mannite sulfate (PGMS).
AB  - In order to reveal the antithrombotic mechanism of propylene glycol mannite
      sulfate (PGMS) on gene level and explore the correlation between PGMS and
      fibrinolytic system, the urokinase-type plasminogen activator (uPA) mRNA
      expression and uPA activity were detected in vitro and in vivo with semi
      quantitative reverse transcription (RT)-PCR and chromogenic method. The results
      showed that PGMS was able to increase uPA activity in dosage-dependent manner in
      rat plasma, which resulted in the increase of rat fibrinolytic activity. The
      change of rat uPA mRNA expression with PGMS was similar to that of uPA activity.
      The results of experiments with cultured cells were similar to those results of
      experiments in vivo. The uPA mRNA expression and activities of cultured cells
      showed increases with PGMS in a concentration-dependent manner. All of these
      results indicated that PGMS may induce the expression of uPA mRNA. The increase
      of uPA mRNA expression may therefore reflect, in part, an increase in the
      stability of uPA mRNA and/or processing of nuclear uPA transcription, which, in
      turn, may increase the uPA activity in rat plasma and trigger the fibrinolytic
      system.

PMID- 16300960
TI  - Involvement of SLP-65 and Btk in tumor suppression and malignant transformation
      of pre-B cells.
AB  - Signals from the precursor-B cell receptor (pre-BCR) are essential for selection
      and clonal expansion of pre-B cells that have performed productive immunoglobulin
      heavy chain V(D)J recombination. In the mouse, the downstream signaling molecules
      SLP-65 and Btk cooperate to limit proliferation and induce differentiation of pre
      B cells, thereby acting as tumor suppressors to prevent pre-B cell leukemia. In
      contrast, recent observations in human BCR-ABL1(+) pre-B lymphoblastic leukemia
      cells demonstrate that Btk is constitutively phosphorylated and activated by the
      BCR-ABL1 fusion protein. As a result, activated Btk transmits survival signals
      that are essential for the transforming activity of oncogenic Abl tyrosine
      kinase.

PMID- 16300961
TI  - Involvement of nectins in the formation of puncta adherentia junctions and the
      mossy fiber trajectory in the mouse hippocampus.
AB  - Synapses are specialized intercellular junctions whose specificity and plasticity
      are mediated by synaptic cell adhesion molecules. In hippocampus, the mossy
      fibers form synapses on the apical dendrites of the CA3 pyramidal cells where
      synaptic and puncta adherentia junctions (PAJs) are highly developed. Synaptic
      junctions are the sites of neurotransmission, while PAJs are regarded as
      mechanical adhesion sites. Cell-cell adhesion molecules nectin-1 and nectin-3
      asymmetrically localize at the pre- and post-synaptic sides of PAJs,
      respectively. To reveal the definitive role of nectins, we analyzed nectin-1-/-
      and nectin-3(-/-) mice. In both the mutant mice, the number of PAJs at the
      synapses between the mossy fiber terminals and the dendrites of the CA3 pyramidal
      cells was reduced. In addition, the abnormal mossy fiber trajectory was observed.
      These results indicate that nectins are involved in the formation of PAJs, which
      maintain the proper mossy fiber trajectory.

PMID- 16300962
TI  - Recombinant production of anti-HIV protein, griffithsin, by auto-induction in a
      fermentor culture.
AB  - Griffithsin (GRFT) is a novel anti-HIV protein isolated from the red alga
      Griffithia sp. The potent anti-viral activity of GRFT against both laboratory and
      primary isolates of HIV at picomolar concentrations makes this protein an
      attractive candidate microbicide to prevent sexual transmission of HIV. Here, we
      describe the recombinant production and purification of a biologically active
      hexa-histidine-tagged GRFT (His-GRFT) from Escherichia coli. To facilitate a
      large-scale production of recombinant His-GRFT, we tested different expression
      conditions to optimize the expression in the cytoplasm of E. coli to increase the
      overall production of soluble His-GRFT. Attempts to express His-GRFT in shake
      flask cultures resulted in a modest yield of soluble His-GRFT, with a large
      accumulation of the protein in inclusion bodies. The use of a fermenter and of a
      rich, auto-inducing medium allowed the total amount of His-GRFT per liter to be
      increased by about 45-fold, with approximately 70% of the protein expressed in
      the soluble fraction. N-terminal sequencing and MALDI-TOF analyses of the
      recombinant His-GRFT confirmed that the initial methionine residue was cleaved
      off. Recombinant His-GRFT showed equivalent activity with natural GRFT, both in
      respect to gp120-binding characteristics as well as anti-HIV activity. Size
      exclusion chromatography analysis showed that both native GRFT and recombinant
      His-GRFT existed as homodimers in solution. The expression system described in
      this work provides a basis for the mass production of GRFT to allow further
      studies of the protein and investigation of therapeutic and preventive strategies
      against HIV.

PMID- 16300963
TI  - Purification and characterization of a soluble form of the recombinant human
      galactose-beta1,3-glucuronosyltransferase I expressed in the yeast Pichia
      pastoris.
AB  - The galactose-beta1,3-glucuronosyltransferase I (GlcAT-I) catalyzes the transfer
      of glucuronic acid from UDP-alpha-D-glucuronic acid onto the terminal galactose
      of the trisaccharide glycosaminoglycan-protein linker region of proteoglycans.
      This enzyme plays a key role in the process of proteoglycan assembly since the
      completion of the linkage region is essential for the conversion of a core
      protein into a functional proteoglycan. To investigate the enzymatic properties
      of human GlcAT-I, we established an expression system for producing a soluble
      form of enzyme in the methylotrophic yeast Pichia pastoris and developed a three
      step purification procedure using a combination of anion exchange, cation
      exchange and heparin chromatographies. This procedure yielded 1.6 mg homogeneous
      enzyme from 200 ml yeast cell culture, with a specific activity value of 1.5
      micromol/min/mg protein. Analysis of the specificity of GlcAT-I towards Galbeta1
      3Gal and Galbeta1-4GlcNAc derivatives known as substrates of the beta1,3
      glucuronosyltransferases, showed that the enzyme exhibited a strict selectivity
      towards Galbeta1-3Gal structures. Thus, the large source of purified active
      enzyme allowed the determination of the kinetic parameters of GlcAT-I towards the
      donor substrate UDP-GlcA and the acceptor substrate digalactoside Galbeta1-3Gal.

PMID- 16300964
TI  - Coexpression of the subunits of T7 DNA polymerase from an artificial operon
      allows one-step purification of active gp5/Trx complex.
AB  - T7 DNA polymerase expression was performed from an artificial operon by cloning
      its cofactor, thioredoxin, downstream of a N-terminal 9xHis-tagged T7 gene 5
      (gp5). Up to 90% of gp5 was soluble in the presence, but not in the absence of
      thioredoxin coexpression suggesting that free-form thioredoxin assisted
      solubilization of gp5. Expression and single-step nickel-agarose affinity
      purification resulted in recovery of an enzyme that was 97% pure. Copurification
      of thioredoxin was observed and the estimated molar ratio of thioredoxin to gp5
      was 1:1 in the purified DNA polymerase complex. Purified T7 DNA polymerase
      exhibited full polymerase activity compared to the commercial enzyme and required
      no exogenous thioredoxin for activity.

PMID- 16300965
TI  - Cortical activation in the processing of passive sentences in L1 and L2: an fMRI
      study.
AB  - The question of whether the bilingual brain processes a first and second language
      (L1 and L2, respectively) differently is a central issue in many psycholinguistic
      and neurolinguistic studies. This study used functional magnetic resonance
      imaging (fMRI) to investigate whether late bilinguals process structurally
      complex sentences in L1 and L2 in different cortical networks. For this purpose,
      we directly compared brain activity during the processing of active and passive
      sentences in both L1 and L2. We asked 36 healthy subjects to judge whether or not
      a presented sentence was semantically plausible. Both L1 and L2 activated the
      left hemispheric language-related regions such as the left inferior frontal,
      superior/middle temporal, and parietal cortices. However, we found different
      activation patterns between L1 and L2 in the processing of passive sentences.
      Passive sentences elicited greater activation than their active counterparts in
      the left pars triangularis, the premotor area, and the superior parietal lobule
      in Japanese, but not in English. Furthermore, there was a significant interaction
      between sentence type (active versus passive) and language (Japanese versus
      English) in the left pars orbitalis. The results of this study indicate that late
      bilinguals use similar cortical regions to comprehend both L1 and L2. However,
      when late bilinguals are presented with structurally complex sentences, the
      involvement of these regions differs between L1 and L2. These results suggest
      that, in addition to age of L2 acquisition and L2 proficiency, differences in
      grammatical construction affect cortical representation during the comprehension
      of L1 and L2.

PMID- 16300966
TI  - Brain correlates of negative and positive visuospatial priming in adults.
AB  - A balance of inhibitory and facilitatory mechanisms is essential for efficient
      and goal-directed behaviors. These mechanisms may go awry in several
      neuropsychiatric disorders characterized by uncontrolled, repetitive behaviors.
      The visuospatial priming paradigm is a well-established probe of inhibition and
      facilitation that has been used to demonstrate behavioral deficits in patients
      with Tourette syndrome and obsessive-compulsive disorder. However, the brain
      correlates of this visuospatial priming paradigm are not yet well established. In
      the present study, we used a visuospatial priming paradigm and event-related
      functional MRI, to probe inhibitory and facilitatory brain mechanisms in healthy
      adult women. When subjects performed the negative priming (i.e., inhibitory)
      task, several regions of the prefrontal cortex were selectively activated
      relative to the neutral condition. Non-overlapping regions of the prefrontal
      cortex were deactivated in the positive priming condition. These results support
      the notion that the prefrontal cortex is involved in both inhibitory and
      facilitatory processing and demonstrate that this visuospatial priming task
      shares brain correlates with other positive and negative priming tasks. In
      conjunction with functional MRI, this visuospatial priming task may be useful for
      studying the pathophysiology of neuropsychiatric disorders in which deficient
      inhibitory processing or excessive facilitation is a feature.

PMID- 16300967
TI  - Declarative memory impairments in Alzheimer's disease and semantic dementia.
AB  - Semantic dementia (SD) and Alzheimer's disease (AD) are both disorders in which
      early pathology affects the temporal lobe yet they produce distinct syndromes of
      declarative memory impairment-loss of established semantic knowledge with
      relatively preserved episodic memory in the former and the converse in the
      latter. Groups with mild SD and mild AD who showed a double dissociation in these
      two aspects of declarative memory were studied-the SD group's episodic memory and
      the AD group's semantic knowledge each being comparable to controls. Positron
      emission tomography and volumetric magnetic resonance imaging were used to map
      deficits in regional cerebral metabolic rate and mesial temporal lobe (MTL)
      atrophy, respectively. Episodic memory impairment in AD was associated with
      dysfunction of an integrated network (mesial temporal lobe, mamillary bodies,
      dorso-mesial thalamus and posterior cingulate). Semantic memory impairment in SD
      was associated with bilateral rostral temporal lobe hypometabolism. The SD group
      had comparable MTL atrophy and hypometabolism to that found in AD but the
      remainder of their limbic-diencephalic network was preserved suggesting that the
      latter explains their ability to acquire new episodic memories. The results
      challenge the view that amnesia in early AD can be explained by the degree of MTL
      damage alone while showing that semantic impairment can occur with damage
      restricted to the rostral temporal lobes.

PMID- 16300968
TI  - Reliability in multi-site structural MRI studies: effects of gradient non
      linearity correction on phantom and human data.
AB  - Longitudinal and multi-site clinical studies create the imperative to
      characterize and correct technological sources of variance that limit image
      reproducibility in high-resolution structural MRI studies, thus facilitating
      precise, quantitative, platform-independent, multi-site evaluation. In this work,
      we investigated the effects that imaging gradient non-linearity have on
      reproducibility of multi-site human MRI. We applied an image distortion
      correction method based on spherical harmonics description of the gradients and
      verified the accuracy of the method using phantom data. The correction method was
      then applied to the brain image data from a group of subjects scanned twice at
      multiple sites having different 1.5 T platforms. Within-site and across-site
      variability of the image data was assessed by evaluating voxel-based image
      intensity reproducibility. The image intensity reproducibility of the human brain
      data was significantly improved with distortion correction, suggesting that this
      method may offer improved reproducibility in morphometry studies. We provide the
      source code for the gradient distortion algorithm together with the phantom data.

PMID- 16300969
TI  - Identification of degenerate neuronal systems based on intersubject variability.
AB  - Group studies implicitly assume that all subjects activate one common system to
      sustain a particular cognitive task. Intersubject variability is generally
      treated as well-behaved and uninteresting noise. However, intersubject
      variability might result from subjects engaging different degenerate neuronal
      systems that are each sufficient for task performance. This would produce a
      multimodal distribution of intersubject variability. We have explored this idea
      with the help of Gaussian Mixture Modeling and Bayesian model comparison
      procedures. We illustrate our approach using a crossmodal priming paradigm, in
      which subjects perform a semantic decision on environmental sounds or their
      spoken names that were preceded by a semantically congruent or incongruent
      picture or written name. All subjects consistently activated the superior
      temporal gyri bilaterally, the left fusiform gyrus and the inferior frontal
      sulcus. Comparing a One and Two Gaussian Mixture Model of the unexplained
      residuals provided very strong evidence for two groups with distinct activation
      patterns: 6 subjects exhibited additional activations in the superior temporal
      sulci bilaterally, the right superior frontal and central sulcus. 11 subjects
      showed increased activation in the striate and the right inferior parietal
      cortex. These results suggest that semantic decisions on auditory-visual compound
      stimuli might be accomplished by two overlapping degenerate neuronal systems.

PMID- 16300970
TI  - Visual working memory for simple and complex features: an fMRI study.
AB  - Visual working memory (VWM) allows us to hold visual information briefly in our
      minds after its disappearance. It is important for bridging the present to the
      immediate past. Previous neuroscience studies on VWM have shown that several
      parietal, frontal, and occipitotemporal brain regions subserve this function.
      Those studies, however, have often focused on VWM for a single property, such as
      color. Yet, in behavior, the capacity of VWM is sensitive to the complexity of to
      be-remembered visual features. How do different brain areas represent VWM for
      visual features of different complexity and for combination of features? To
      address this question, we used functional MRI to study the response profile of
      several brain regions in three VWM tasks. In all tasks, subjects saw 1 to 7
      colored polygons and had to remember their color (a simple feature), shape (a
      complex feature), or both color and shape. Behavioral performance showed that VWM
      reached capacity limit at about 3 colors, 2 shapes, and 2 compound objects. In
      the fMRI data, we found different functional profiles for frontal, parietal, and
      occipitotemporal regions. Specifically, the posterior parietal cortex was
      sensitive to both featural and VWM load manipulations. The prefrontal regions
      were sensitive to VWM load manipulation but relatively insensitive to featural
      differences. The occipitotemporal regions were sensitive to featural differences,
      but not to VWM load manipulation. We propose that the response properties of
      these regions can jointly account for several findings in human VWM behavior.

PMID- 16300971
TI  - A streamlined method to predict hepatic clearance using human liver microsomes in
      the presence of human plasma.
AB  - INTRODUCTION: Human liver microsomal incubations are often used to predict the
      metabolic lability of new chemical entities. The clearance values are scaled-up
      from in vitro data and mathematically corrected for plasma protein binding, or in
      some cases the free fraction ratio of plasma to microsomes, using well
      established scaling methods such as the well-stirred model. This can be time
      consuming for multiple compounds since it requires separate experiments to
      determine in vitro lability, and free fraction. METHODS: We attempted to
      streamline clearance predictions by combining experiments into one. Firstly, we
      combined the free fraction experiments into one free fraction ratio by measuring
      the partitioning of compound between plasma and microsomes, and by applying this
      experimental ratio to clearance predictions found that it performed at least as
      well as free fractions determined separately. We also incubated compounds with
      plasma added to the incubation mixture and compared the predicted clearances to
      values determined using traditional mathematical protein binding corrections.
      RESULTS: Consistently, incubations with added plasma resulted in CL predictions
      closer to literature values than incubations only mathematically corrected for
      protein binding. For example, incorporating plasma into a ketamine incubation
      resulted in a CL value of 15.1 mL/min/kg, compared with a value of 10.2 using
      mathematical binding corrections. The literature value is 16.4 mL/min/kg.
      DISCUSSION: This work characterizes this new method and compares it to the
      traditional microsomal incubation method using several literature compounds, and
      suggests that streamlining the methods may generate quality data faster and with
      less resource investment.

PMID- 16300972
TI  - Glucosamine decreases expression of anabolic and catabolic genes in human
      osteoarthritic cartilage explants.
AB  - OBJECTIVE: To investigate the effect of glucosamine (GlcN) in a human
      osteoarthritic explant model on expression of genes involved in anabolic and
      catabolic activities of chondrocytes. METHODS: Human osteoarthritic explants,
      obtained during knee arthroplasty surgery, were pre-cultured (3 days) and treated
      with glucosamine-hydrochloride (GlcN-HCl) or glucosamine-3-sulphate (GlcN-S) at
      0.5mM and 5mM (4 days). RNA was isolated from the explants and real time RT-PCR
      was performed. Additionally, total matrix metalloproteinase (MMP) activity was
      measured in culture medium. RESULTS: Addition of 5mM GlcN led to significant down
      regulation of aggrecan (2.65-7.73-fold) and collagen type II (7.75-22.17-fold)
      gene expression, indicating inhibited anabolic activity. Considering catabolic
      activities, 5mM GlcN significantly down-regulated aggrecanase-1 and MMP3 and 5mM
      GlcN-S additionally down-regulated aggrecanase-2 and tissue inhibitor of MMP gene
      expression significantly. Gene expression was not significantly altered by 0.5mM
      GlcN. Total MMP activity in culture medium was only significantly reduced after
      addition of 5mM GlcN-HCl. CONCLUSION: The effects of GlcN on gene expression in a
      human osteoarthritic explant model suggest that enzymatic breakdown of the extra
      cellular matrix might be reduced by the addition of 5mM GlcN. Additionally,
      restoration of already damaged cartilage is not to be expected, because gene
      expression of anabolic genes is also down-regulated. We suggest that
      chondroprotective properties of GlcN in vivo may be based on inhibiting further
      degradation due to catabolic activities, rather than on the ability to rebuild
      cartilage.

PMID- 16300973
TI  - Nitric oxide stimulates PC12 cell proliferation via cGMP and inhibits at higher
      concentrations mainly via energy depletion.
AB  - We investigated the mechanisms by which nitric oxide (NO) from an NO donor
      (DETA/NO) regulates proliferation of pheochromocytoma PC12 cells. The NO donor
      stimulated proliferation at low concentrations, but reversibly and completely
      inhibited proliferation at higher concentrations. The stimulation (but not the
      inhibition) of proliferation was apparently due to NO stimulation of soluble
      guanylate cyclase to produce cGMP, as it was prevented by a specific cyclase
      inhibitor (ODQ), and replicated by a cell-permeable form of cGMP. The NO-induced
      cytostasis was not reversed by inhibitors of MEK kinase or poly(ADP
      ribose)polymerase, or by treatments that bypass inhibition of ribonucleotide
      reductase or ornithine decarboxylase. Cytostatic concentrations of DETA/NO
      strongly inhibited respiration of PC12 cells, and specific respiratory inhibitors
      (rotenone, myxothiazol, or azide) caused complete cytostasis. Uridine and
      pyruvate reversed the cytostasis induced by the specific respiratory inhibitors,
      but not that induced by DETA/NO. However, the combination of uridine, pyruvate,
      and N-acetyl-cysteine did reverse DETA/NO-induced cytostasis. DETA/NO strongly
      and progressively inhibited glycolysis measured by glucose consumption, lactate
      production, and ATP level, and a specific glycolytic inhibitor (5 mM 2-deoxy-d
      glucose) caused complete cytostasis. Our results indicate that NO at low
      concentrations increases cell proliferation via cGMP, while high concentrations
      of NO block proliferation via inhibition of both glycolysis and respiration,
      causing energy depletion.

PMID- 16300974
TI  - Pain induced by low-grade stress in patients with fibromyalgia and chronic
      shoulder/neck pain, relation to surface electromyography.
AB  - The mechanisms of pain causation in fibromyalgia (FMS) and chronic shoulder/neck
      pain (SNP) are still debated. We wanted to compare muscle activity and pain
      development during and after low-grade mental stress in FMS and SNP patients.
      Twenty-three women with FMS, 29 women with chronic SNP and 35 healthy women
      performed a stressful task lasting 60 min followed by a 30 min recovery period.
      We recorded surface electromyography over the trapezius, neck, temporalis and
      frontalis muscles. Subjects reported their pain at the corresponding locations
      together with the development of fatigue and perceived tension. Significant
      differences between FMS and SNP groups were not observed either for muscular or
      subjective responses. SNP patients and controls responded with more pain in the
      trapezius and neck regions than in the forehead, in contrast to FMS patients who
      had a more generalized pain response. Development of pain, tension and fatigue
      was not related to muscle activity for any group. We conclude that FMS and SNP
      patients have similar pain and electromyographic responses. The results suggest
      that similar pathophysiological mechanisms are involved although the responses
      are more generalised in FMS than in SNP patients. Muscular activity did not
      explain the pain which developed during the stressful task for either group. Pain
      lasted longer during recovery in both FMS and SNP patients compared to healthy
      controls, possibly a result of disease-related sensitisation in pain pathways.

PMID- 16300975
TI  - Impairments as measured by ISS do not greatly change between one and eight years
      after CRPS 1 diagnosis.
AB  - BACKGROUND: Complex Regional Pain Syndrome type 1 (CRPS 1) is a potentially
      incapacitating complication in which pain seems to be the most disabling factor.
      We performed a late follow up study of a well-defined CRPS 1 population more than
      eight years after diagnosis. The relationships between early and late impairments
      were studied with a view to outcome prediction and to investigate possible
      differences in long-term impairments according to initial CRPS 1 subdiagnosis
      (i.e. "warm" or "cold", diagnosed according to skin temperature measured via
      infrared thermometer). METHODS: We again measured patients using the Impairment
      Level SumScore (ISS) (T8). These data were compared with earlier ISS measurements
      at CRPS diagnosis (T0) and after one year's treatment (T1). Correlations were
      determined between these measures. RESULTS: Forty-five patients participated in
      the present study. Total median ISS improved by 55% (statistically/clinically
      significant) after one year's treatment (T1), and worsened (non-significantly) by
      14% from T1 to T8 - without differences according to original subdiagnosis. ISS
      correlations were stronger for T1 vs. T8 than for T0 vs. T1 or T0 vs. T8, being
      strongest for the ISS factors related to pain. CONCLUSIONS: Considerable
      impairments, as measured by ISS, are still present over eight years after first
      CRPS 1 diagnosis. These do not greatly change between one and eight years post
      diagnosis. ISS outcomes are similar for "cold" and "warm" CRPS 1 diagnostic
      subgroups. Component ISS scores associated with pain appear to possess greatest
      predictive power.

PMID- 16300976
TI  - Psychometric evaluation of multidimensional pain inventory (Swedish version) in a
      sample of elderly people.
AB  - OBJECTIVES: The aim was to psychometrically evaluate the Swedish version of the
      Multidimensional Pain Inventory (MPI-S) and the "brief screening version of MPI
      S" for use in an elderly sample. METHODS: This study comprised 175 people aged 76
      99 years reporting pain and in need of help to manage daily living. The
      instrument's factor structures were investigated through factor analyses,
      convergent and discriminant validity were assessed through inter-scale
      correlations and correlations with items from SF-12. Reliability was assessed by
      Cronbach's alpha. RESULTS: The full-length version of MPI-S did not, in general,
      show any satisfactory validity and reliability when used among elderly. It had
      acceptable convergent and discriminant validity, but the factor analysis did not
      show a good model fit. Low alpha values were found for most of the sub-scales.
      However, the brief screening version of MPI showed acceptable validity and
      reliability, except for rather low alpha values in sections 3 and 4. CONCLUSION:
      The MPI-S instrument may not be very useful for measuring pain among frail
      elderly. The brief screening version may instead be a better alternative to the
      full version of the MPI-S. However, the small number of observations may be the
      reason to the lack of fit, and further studies are warranted.

PMID- 16300977
TI  - Interaction between tramadol and two anti-emetics on nociception and
      gastrointestinal transit in mice.
AB  - BACKGROUND: Clinical studies suggest that tramadol-induced analgesia is partially
      antagonized by ondansetron. AIMS: To investigate the type of interaction between
      tramadol and two anti-emetics on antinociception and gastrointestinal transit in
      mice. METHODS: We assessed the antinociceptive (acetic acid writhing test,
      plantar test) and antitransit (charcoal meal) effects of tramadol individually,
      and combined with ondansetron or droperidol in female Swiss CD-1 mice.
      Isobolograms and analysis of variance were used to determine the type of
      interaction. RESULTS: In the writhing test, tramadol, ondansetron and droperidol,
      each induced dose-related inhibition of nociception. The ED(50)'s were: tramadol
      4.2+/-0.33 mg kg(-1); ondansetron 1.03+/-0.05 mg kg(-1), and droperidol 1.00+/
      0.14 mg kg(-1). Dose-response curves were also obtained with tramadol combined
      with ondansetron or droperidol at 1:1 fixed ratios. The isobolographic analysis
      demonstrated antagonism for both combinations. In the plantar test, the ED(50)
      for tramadol was 51.4+/-2.3 mg kg(-1), but no dose-response curves could be
      obtained with ondansetron or droperidol individually. The interaction was
      assessed from dose-response curves to tramadol in the presence of a fixed dose of
      ondansetron (0.1 mg kg(-1)) or droperidol (0.05 mg kg(-1)). The results show
      antagonism between tramadol-ondansetron (p<0.05) and no interaction for the
      tramadol-droperidol combination. Both anti-emetics antagonized the antitransit
      effects of tramadol. CONCLUSIONS: The interaction of tramadol with ondansetron or
      droperidol on antinociception can be antagonistic or additive, depending on the
      type of stimuli. Both anti-emetics antagonize the anti-transit effects of
      tramadol. The results demonstrate antagonism between tramadol and the two anti
      emetics for analgesia and inhibition of gastrointestinal transit, supporting
      previous clinical studies.

PMID- 16300978
TI  - Computation of through-space NMR shielding effects by functional groups common to
      peptides.
AB  - The GIAO-HF method in Gaussian 03 was employed to calculate the isotropic
      shielding values of a covalently bonded hydrogen probe and to predict the through
      space proton NMR shielding increment surfaces near models of simple structures
      containing functional groups common to peptides. The functional groups examined
      include the carboxylate anion, carboxylic acid, amide, amino, ammonium and
      guanidinium groups. Our previously developed methodology involving the use of
      diatomic hydrogen as a probe of through-space shielding effects was employed.
      Substantial shielding or deshielding effects were observed only in the cases of
      the charged (ionic) groups, each of which displayed shielding or deshielding
      effects of greater than 1 ppm at distances comparable to those observed in
      peptides. Equations for predicting the shielding increments of these groups as a
      function of the Cartesian coordinate position of the affected proton were
      determined. The validity of using simple structures as models of shielding by
      comparable functional groups in peptides was confirmed by computing the shielding
      effects at selected positions above a model of glycylglycylglycine and its
      hydrogen-bonded dimer. Knowledge of these through-space shielding effects should
      aid in the tertiary structure determination of peptides by NMR.

PMID- 16300980
TI  - [Radiotherapy for PSA failure after prostatectomy: which volumes?].
AB  - After prostatectomy, radiotherapy is a potential curable treatment. From the
      surgery series, it is possible to identify all the localization at risk in case
      of biochemical relapse after prostatectomy. The target volume of irradiation has
      to be defined according to the pathological findings. The CTV is limited to the
      pelvic fascia laterally, to the anterior wall of the rectum behind. The inferior
      limit includes the anastomosis, and the superior is easier to define with the
      length of the prostatic gland. The inclusion of area of seminal vesicles and
      pelvic node areas should be discussed. The use of surgical clips on the
      anastomosis and image fusionning techniques including the preoperative imaging
      would help physicians to define the CTV's limits.

PMID- 16300981
TI  - [Soft sarcoma tissue of extremities: medical imagery in post-therapeutic follow
      up].
AB  - After treatment of primary soft tissue sarcoma, a third of patients will develop
      local or distant (lung in 90% of cases) recurrence. For an individual patient,
      the issue of cancer recurrence is a binary event. However, when developing
      surveillance strategies for large groups of patients, knowledge of the risks
      (tumor biology, natural history of the disease), the benefits (potential efficacy
      of salvage therapy) and diagnosis test performances is necessary to formulate a
      rationale and resource effective follow-up algorithm.

PMID- 16300982
TI  - [Radiation-induced sarcomas after breast cancer: experience of Institute Curie
      and review of literature].
AB  - Adjuvant radiotherapy to the breast plays a significant role in preventing local
      failure in women treated for early stage breast cancer. This fact is supported by
      multiple clinical trials demonstrating that adjuvant radiotherapy decreases the
      risk of local recurrence and increases the rate of breast preservation, and
      actually the rules of adjuvant breast irradiation are clearly established.
      Sarcomas are a rare but recognized complication of radiation therapy for breast
      carcinoma, and are associated with poor prognosis. The first case of a bone
      sarcoma after radiation therapy of breast cancer was described by Beck in 1922.
      In 1948, Cahan et al. defined the criteria for diagnosis of radiation-induced
      sarcoma. Since then, some studies have reported the incidence of radiation
      induced sarcoma after radiotherapy for different cancers. This article reports
      and discusses the incidence, management and treatment outcome of radiation
      induced sarcomas occurring after radiotherapy for breast cancer in our institute.
      The incidence, histology, latency of appearance, genesis, their treatment and the
      prognostic factors of these rare tumors are discussed and the literature is
      reviewed.

PMID- 16300983
TI  - [Surgery of retroperitoneal sarcomas].
AB  - Retroperitoneal sarcomas comprise approximately 15% of all soft tissue sarcomas
      and 50% of all retroperitoneal tumours. Helical CT of the abdomen and pelvis,
      with selective use of MRI will establish the extent of the tumour, its
      retroperitoneal location, the degree of necrosis, and the evidence of metastasis.
      A CT guided core needle biopsy is the optimal pre operative tissue sampling. A
      complete surgical resection is the mainstay of the treatment with a rim of normal
      tissue that often requires removal of adjacent organs. The 5-year probability of
      local control is approximately 50%. The role of adjuvant therapy is evolving and
      at present should not be used outside the investigational setting.

PMID- 16300984
TI  - Mycobacterial trehalose-containing glycolipid with immunomodulatory activity on
      human CD4+ and CD8+ T-cells.
AB  - Protection against Mycobacterium tuberculosis is based on cell-mediated immunity,
      most importantly involving CD4+ and CD8+ T-cell subsets. One of the key features
      of the tubercle bacillus is its cell envelope, characterized by extremely
      abundant and specific lipids. The cell-surface glycolipid 2,3-di-O-acyl-trehalose
      (DAT) has been consistently found in M. tuberculosis strains. In this study,
      analysis of proliferation, activation markers and cytokine release was performed
      in human peripheral blood mononuclear cells (PBMC) activated in the presence and
      absence of DAT. We present evidence that mycobacterial DAT is able to reduce
      antigen-induced proliferation of human CD4+ and CD8+ T-cell subsets. We show that
      the effect is associated with a decrease of cells expressing the T-cell surface
      activation markers CD25 and CD69, and down-modulation of IL-2, IL-12, TNF-alpha
      and IL-10 cytokines. Data indicating that fine acyl chain structural variations
      in the trehalose-containing lipid may be involved in the degree of immune
      modulation are also presented.

PMID- 16300985
TI  - Real-time analysis of human immunodeficiency virus type 1 Env-mediated membrane
      fusion by fluorescence resonance energy transfer.
AB  - Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env)-mediated
      membrane fusion occurs as a sequence of events that is triggered by CD4 binding
      to the Env gp120 subunit. In this study, we analyzed the dynamics of Env-mediated
      membrane fusion at the single-cell level using fluorescent fusion proteins and
      confocal laser fluorescent microscopy. Either enhanced cyan or yellow fluorescent
      protein (CFP and YFP, respectively) was fused to the end of the cytoplasmic
      regions of the HIV-1 receptors (CD4 and CCR5) and Env proteins. Real-time imaging
      of membrane fusion mediated by these recombinant proteins revealed that the
      kinetics of fusion in our system was faster than that previously reported.
      Analysis of the receptor interaction by fluorescence resonance energy transfer
      (FRET) at the single-cell level demonstrated a tendency for oligomerization of
      CD4-CD4, but not of CD4-CCR5, in the absence of Env-expressing cells. However,
      when Env-expressing cells attached to the receptor cells, FRET produced by CD4
      CCR5 interaction was increased; the FRET intensity began to decline before the
      formation of the fusion pore. These changes in FRET may represent the temporal
      association of these receptors, triggered by gp120 binding, and their
      dissociation during the formation of the fusion pore. In addition, the FRET
      analysis of receptor interactions in the presence of fusion inhibitors showed
      that not only inhibitors acting on CCR5 but also the gp41-derived peptide T-20
      interfered with CD4-CCR5 interaction during fusion. These data suggest that T-20
      could affect the formation of Env-receptors complexes during the membrane fusion.

PMID- 16300986
TI  - Low growth ability of recent influenza clinical isolates in MDCK cells is due to
      their low receptor binding affinities.
AB  - Madin Darby canine kidney (MDCK) cells have generally been used to isolate
      influenza viruses from patients. However, in recent years, most fresh isolates of
      the H3N2 subtype have shown poor growth in MDCK cell cultures. Such low-growth
      viruses were often converted to high-growth viruses after several passages
      through MDCK cell cultures. In the present study, viruses were found to lose a
      potential glycosylation site near the receptor-binding pocket of hemagglutinin
      (HA), at the same time as they acquired the high-growth property. The growth
      curves of viruses in MDCK cell cultures revealed that multi-cycle replication did
      not function well in the low-growth viruses. However, the production of progeny
      viruses within a single cycle of growth did not differ much between the low- and
      high-growth viruses. The high-growth viruses showed higher infection efficiency
      in MDCK cell cultures than the low-growth viruses. The HA genes of both low- and
      high-growth viruses were separately cloned into the SV40 vector to compare their
      receptor binding affinities. The HA of high-growth viruses showed a much higher
      receptor binding affinity than that of low-growth viruses, when assayed by
      hemadsorption and the release kinetics of erythrocytes with bacterial
      neuraminidase. Reverse genetics studies demonstrated that HA was a crucial
      determinant for multi-cycle replication in MDCK cell cultures. Taken together,
      these results demonstrate that inefficient multi-cycle growth of fresh isolates
      is due to their low receptor binding affinities.

PMID- 16300987
TI  - Statins in rheumatology.
AB  - Statins were developed for the treatment of lipid disorders and have been proved
      to reduce cardiovascular morbidity and mortality when used for primary or
      secondary prevention. Beneficial effects in patients with osteoporotic fractures
      or rheumatoid arthritis (RA) have been suggested but remain unproven.
      Cardiovascular morbidity and mortality are increased in patients with RA or
      systemic lupus erythematosus, who should undergo serum lipid assays. When these
      show dyslipidemia, statin therapy should be started according to current
      recommendations.

PMID- 16300988
TI  - Standardization of measuring power output during wheelchair propulsion on a
      treadmill Pitfalls in a multi-center study.
AB  - OBJECTIVE: In a multi-center study the power output of wheelchair propulsion,
      attained by a wheelchair drag test, differed among rehabilitation centers. The
      purpose of this study was to investigate what causes the differences in drag
      force among centers. METHODS: A set of standardized drag tests was performed
      while systematically varying the calibration set of the force transducer, the
      tester and the wheelchair. In addition, the actual calibrated velocity and slope
      of the treadmill were measured. RESULTS: Difference in drag force among centers
      was due to variation in wheelchair set-up and differences in the slopes between
      treadmills. The drag force was not significantly different when different testers
      performed the test. The belt velocity in almost all centers was lower than the
      manufacturer specified (assumed) velocity. CONCLUSION: The drag test appeared a
      robust test as far as the tester is considered. Variation in wheelchairs and
      differences in the actual slopes of the treadmills affected the imposed drag
      force. The assumed velocity of the treadmill led to an overestimation of the
      power output. The power output in the multi-center study should be recalculated
      using the measured velocities and the wheelchair set-up should be more
      standardized.

PMID- 16300989
TI  - Comparative studies of intracellular Ca2+ in strongly and weakly metastatic rat
      prostate cancer cell lines.
AB  - The metastatic ability of prostate cancer cells involves differential expression
      of ionic mechanisms. In the present study, using electrophysiological recordings
      and intracellular Ca2+ measurements, we investigated Ca2+ related signalling in
      two rat prostate cancer (MAT-LyLu and AT-2) cell lines of markedly different
      metastatic potential. Whole-cell voltage clamp experiments indicated the absence
      of an inward current carried through voltage-dependent Ca2+ channels in either
      cell line. A Ca2+-dependent component was also absent in the voltage-activated
      outward K+ currents. Indo-1 microfluorimetry confirmed these results and also
      revealed marked differences in the resting level of intracellular Ca2+ and the
      ability of the two cell lines to regulate intracellular Ca2+. The weakly
      metastatic AT-2 cells displayed a significantly higher resting intracellular Ca2+
      than the related but strongly metastatic MAT-LyLu cell line. Increasing
      extracellular K+ decreased intracellular Ca2+ in the AT-2 but had no effect on
      intracellular Ca2+ levels in the MAT-LyLu cells. Furthermore, increasing
      extracellular Ca2+ increased intracellular Ca2+ in AT-2 but, again, had no effect
      on MAT-LyLu cells. These results suggested the presence of a tonic, voltage
      independent Ca2+ permeation mechanism operating specifically in the AT-2 cells.
      The influx of Ca2+ into the AT-2 cells was suppressed by both CdCl2 (100-300
      microM) and SKF-96365 (10-30 microM). It is concluded that the strongly
      metastatic MAT-LyLu cell line lacks a voltage-independent basal Ca2+ influx
      mechanism that is present in the weakly metastatic AT-2 cells.

PMID- 16300990
TI  - Expression of procollagen C-proteinase enhancer-1 in the remodeling rat heart is
      stimulated by aldosterone.
AB  - Excessive collagen deposition is a common complication of myocardial infarction
      that causes progressive heart disease. Several pro-fibrotic cytokines and
      hormones, including aldosterone, control this process. Procollagen processing by
      procollagen C-proteinase(s) is critical for collagen deposition and is
      potentiated by procollagen C-proteinase enhancer proteins (PCPEs). We have shown
      previously that, in addition to stimulation of collagen I expression, aldosterone
      increases PCPE-1 expression in cultured heart fibroblasts. The present study was
      designed to examine whether aldosterone acts similarly in vivo. Rats underwent
      coronary artery ligation to induce myocardial infarction. They were then left
      either untreated (control) or treated with spironolactone (an aldosterone
      receptor antagonist) for 5 weeks when they were sacrificed and their hearts
      removed for analysis. In situ hybridization co-localized PCPE-1 and collagen I
      mRNAs to fibroblasts surrounding the scar region and adjacent blood vessels. The
      levels of both transcripts in the remodeling myocardium of untreated rats
      increased twofold as compared to sham-operated controls, an increase greatly
      reduced by spironolactone. Correspondingly, a 2-5 fold increase in PCPE-1 and
      collagen I was observed in the hearts of untreated rats as compared to both the
      spironolactone-treated and sham-operated controls. The results establish
      aldosterone as a physiological stimulator of PCPE-1 expression in the remodeling
      myocardium after infarction. Since PCPE-1 itself is a positive regulator of
      collagen deposition, this finding suggests PCPE-1 as a new potential target for
      intervention with cardiac fibrosis.

PMID- 16300991
TI  - Transplantation of rat hepatic stem-like (HSL) cells with collagen matrices.
AB  - Organ restitution using somatic stem cells is of great clinical interest. Recent
      advances in the field of tissue engineering have demonstrated that the use of
      collagen matrices as scaffolds facilitates tissue reconstruction. Here, we
      examine the efficacy of transplantation of HSL cells, a previously established
      liver epithelial cell line with a potential for differentiation, using collagen
      scaffolds. To this end, HSL cells were transplanted into Nagase's analbuminemic
      rat with spongy or gelatinous type I collagen matrices. Consequently,
      immunohistochemical analyses and genomic PCR experiments revealed engraftment of
      the transplanted cells. Furthermore, the levels of serum albumin in recipient
      rats were found to increase up to 2.5-fold relative to controls after
      transplantation. These findings suggest that HSL cells are able to differentiate
      into functional hepatocytes in vivo, and that biodegradable collagen matrices
      enhance this phenomenon by providing an appropriate microenvironment for
      hepatocytic repopulation.

PMID- 16300992
TI  - Breast milk as a source for acquisition of cytomegalovirus (HCMV) in a premature
      infant with sepsis syndrome: detection by real-time PCR.
AB  - Symptomatic disease due to human cytomegalovirus (HCMV) has been increasingly
      recognized in low birth weight (LBW) premature infants. Breast milk has been
      identified as a potential source for these infections. At approximately 60 days
      of life a LBW, premature infant was diagnosed with HCMV sepsis syndrome,
      prompting further investigation of the source for HCMV acquisition. The infant
      had received a combination of both fresh and frozen breast milk from his mother
      throughout his first 2 months of life. We utilized a real-time PCR assay for HCMV
      DNA to retrospectively examine viral genome copy number in serial samples of
      stored, frozen breast milk. This analysis indicated an increase in breast milk
      viral load over the first 45 days of life, heralding the HCMV sepsis syndrome
      that was observed clinically. Real-time PCR may be a useful tool in the
      evaluation of HCMV viral load in breast milk.

PMID- 16300993
TI  - Localization of cholesterol, phosphocholine and galactosylceramide in rat
      cerebellar cortex with imaging TOF-SIMS equipped with a bismuth cluster ion
      source.
AB  - Time-of-flight secondary-ion-mass-spectrometry (TOF-SIMS) was utilized to address
      the issue of co-localization of cholesterol, phosphocholine and
      galactosylceramide in rat cerebellar cortex. Rat cerebellum was fixed, freeze
      protected by sucrose, frozen and sectioned by cryoultramicrotomy and dried at
      room temperature. The samples were analyzed in an imaging TOF-SIMS instrument
      equipped with a Bi(1-7)+-source. The cholesterol signal (m/z 369 and 385) was
      localized in Purkinje cells and in nuclei of granular layer cells. The
      phosphocholine headgroup of phosphatidylcholine and sphingomyelin was localized
      by imaging a specific fragment (m/z 86). This signal was localized in the
      molecular layer of cerebellar cortex, in Purkinje cells and in parts of the
      granular layer probably representing the synapse-rich glomeruli. The
      galactosylceramide was localized by imaging the quasi-molecular ions at m/z 835
      and 851, showed a clear colocalization with cholesterol, but also a specific
      localization in dots (diameter <or=700 nm) in the molecular layer in the vicinity
      of Purkinje cells, at Purkinje cells and at cells in the granular layer. The
      results show a heterogeneous distribution of lipids between different cell types
      not previously described. In order to avoid redistribution artefacts, controls
      were made by a technique, based on high pressure freezing ,freeze fracturing and
      freeze drying of samples which were then analyzed by bombardment with a Bi3+
      liquid metal ion gun. The galactosylceramide and cholesterol were found
      distributed as spots in the granular layer. The spots were of homogeneous size
      with a diameter of <700 nm. Although the galactosylceramide and cholesterol were
      localized to the same areas, there were clear differences in their distribution
      at higher resolution.

PMID- 16300994
TI  - A systematic study of yeast sterol biosynthetic protein-protein interactions
      using the split-ubiquitin system.
AB  - Sterol biosynthesis occurs in the ER and most sterol biosynthetic enzymes have
      transmembrane domains. However, due to difficulties in characterizing membrane
      protein-protein interactions, the nature of the sterol biosynthetic complex as
      well as in vivo interactions between various enzymes have not been described. We
      employed a split-ubiquitin membrane protein yeast two-hybrid system to
      characterize interactions between sterol biosynthetic proteins. Fourteen bait
      constructs were co-transformed into a reporter yeast strain with 14 prey
      constructs representing all sterol enzymatic reactions beginning with the
      synthesis of squalene. Our results not only confirmed several previous
      interactions, but also allowed us to identify novel interactions. Based on these
      results, ergosterol biosynthetic enzymes display specific protein-protein
      interactions forming a functional complex we designate, the ergosome. In this
      complex, Erg11p, Erg25p, Erg27p, and Erg28p appear to form a core center that can
      interact with other enzymes in the pathway. Also Erg24p and Erg2p, two enzymes
      that are sensitive to morpholine antifungals, appear to interact with one
      another; however, the profile of protein interaction partners appears to be
      unique. Erg2p and Erg3p, two enzymes catalyzing sequential reactions also appear
      to have different interaction partners. Our results provide a working model as to
      how sterol biosynthetic enzymes are topologically organized not only in yeast but
      in plant and animal systems that share many of these biosynthetic reactions.

PMID- 16300995
TI  - To 'B' regulated: B cells as members of the regulatory workforce.
AB  - Until recently, immune regulation was thought to be predominantly mediated by
      specialized subsets of T lymphocytes. However, although B lymphocytes have
      previously been shown to have regulatory properties in autoimmunity, a recent
      report by Knoechel et al. establishes a role for B lymphocytes in the control of
      pathogenic autoreactive T cell responses arising when the number of lymphocytes
      is abnormally low (lymphopenia).

PMID- 16300996
TI  - Lymphocyte selection by starvation: glucose metabolism and cell death.
AB  - It has recently been shown by Ciaofani and Zuniga-Pflucker that the Notch
      signaling pathway is important in the regulation of thymocyte glucose metabolism
      during beta-selection. Control of cell metabolism has key roles in the regulation
      of cell death pathways. Changes in glucose metabolism might affect cell death
      pathways and be crucial in the development and selection of T lymphocytes.

PMID- 16300997
TI  - Lipid biology of Apicomplexa: perspectives for new drug targets, particularly for
      Toxoplasma gondii.
AB  - Development of effective therapies for intracellular eukaryotic pathogens is a
      serious challenge, given the protected location of these pathogens and the
      similarity of their biology to that of the host. Identifying cellular processes
      that are unique to the parasite is therefore a crucial step towards defining
      appropriate drug targets. In the case of the apicomplexan parasite Toxoplasma
      gondii, the need to find alternative treatments is imperative because of the poor
      tolerability and frequent side-effects associated with existing therapeutic
      strategies. The discovery that the parasite uses lipid synthetic pathways which
      are different from, or absent in, the mammalian host is now driving a renewed
      interest in T. gondii lipid biology. Recent achievements in this field are
      promising and suggest that the elucidation of lipid pathways will provide new
      opportunities for designing potent antiparasitic strategies.

PMID- 16300998
TI  - Two words colliding: resistance to changes in the scientific names of animals-
      Aedes vs Stegomyia.

PMID- 16300999
TI  - Risk factors in the spread of leishmaniases: towards integrated monitoring?
AB  - Environmental changes, immune status and treatment failure constitute the three
      major risk factors for the (re-)emergence and spread of leishmaniases. Except for
      Leishmania-HIV co-infection, these risk factors are not systematically monitored
      and their interaction is poorly studied and understood. Recently, the
      multidisciplinary network Leish-Med was launched to document this issue around
      the Mediterranean and to promote transborder control strategies.

PMID- 16301000
TI  - Multilocus consensus genetic maps (MCGM): formulation, algorithms, and results.
AB  - In process of creating genetic maps different labs/research groups obtain
      overlapping parts of the map. Merging these parts into one integrative map is
      based on looking for maximum shared marker orders among the maps. Really, not all
      shared markers of such maps have consensus order that obstructs building of the
      integrative maps. In this paper we propose a new approach to build verified
      multilocus consensus genetic maps in which shared markers always are integrated
      in stable consensus order. The approach is based on combined analysis of initial
      mapping data rather than manipulating with previously constructed maps. We show
      that more effective and reliable solutions may be obtained based on "synchronized
      ordering" facilitated by cycles of "re-sampling-->ordering-->removing unstable
      markers". The proposed formulation of consensus genetic mapping can be considered
      as a version of traveling salesperson problem (TSP) that we refer to as
      synchronized-TSP. From the viewpoint of optimization, synchronized-TSP belongs to
      discrete constrained optimization problems. Earlier we developed new powerful and
      fast guided evolution strategy algorithms for some types of discrete constrained
      optimization. These algorithms were used here as a basis for solving more
      challenging problems of consensual marker ordering.

PMID- 16301001
TI  - Insulin-dependent diabetes loci Idd5 and Idd9 increase sensitivity to
      experimental autoimmune encephalomyelitis.
AB  - The spontaneous development of autoimmune diabetes in NOD mice suggests that they
      are unable to establish and maintain immunologic self-tolerance. Congenic NOD
      mice expressing B10-derived alleles are protected from pancreatic beta cell
      destruction and autoimmune diabetes. To determine if the B10 alleles in loci Idd5
      and Idd9 could influence susceptibility to autoimmunity in other organs, we
      compared MOG35-55-induced EAE in NOD mice to that of diabetes-resistant
      NOD.B10.Idd5 and NOD.B10.Idd9 mice. Surprisingly, the severity and chronicity of
      EAE were enhanced in the diabetes-resistant congenic mice. Our findings indicate
      that some alleles may influence susceptibility to immune-mediated damage in an
      organ or tissue-specific fashion, and highlight the necessity of disease-specific
      investigations.

PMID- 16301002
TI  - Intracellular trafficking of plasmids during transfection is mediated by
      microtubules.
AB  - Little is known about how plasmids move through the cytoplasm to the nucleus. It
      has been suggested that the dense latticework of the cytoskeleton impedes free
      diffusion of large macromolecules, including DNA. However, since transfections do
      work, there must be mechanisms by which DNA circumvents cytoplasmic obstacles.
      One possibility is that plasmids become cargo on cytoskeletal motors, much like
      viruses do, and move to the nucleus in a directed fashion. Using microinjection
      and electroporation approaches in the presence of drugs that alter the dynamics
      and organization of the cytoskeleton, we show that microtubules are involved in
      plasmid trafficking to the nucleus. Further, by co-injecting inhibitory
      antibodies, we find that dynein likely facilitates this movement. These results
      were confirmed using an in vitro spin-down assay that demonstrated that plasmids
      bind to microtubules through adaptor proteins provided by cytoplasmic extracts.
      Taken together, these results suggest that plasmids, like most viruses, utilize
      the microtubule network and its associated motor proteins to traffic through the
      cytoplasm to the nucleus.

PMID- 16301003
TI  - Angiotensin II-dependent vascular alterations in young cardiomyopathic hamsters:
      role for oxidative stress.
AB  - Recent studies indicate the presence of vascular alterations in 2-month-old
      Syrian cardiomyopathic hamsters (SCH). These alterations include enhanced
      angiotensin-converting enzyme (ACE) activity in the aorta, increased contractile
      response to angiotensin II and impaired vasorelaxation to acetylcholine in
      norepinephrine-precontracted aortic rings. The mechanisms leading to these
      vascular alterations are not known nor has their relationship to the cardiac
      abnormalities been established. We assessed the status of the cardiovascular
      system of 2-month-old hamsters first to establish if the observed vascular
      alterations are secondary to cardiac dysfunction, and second to examine the role
      of oxidative stress in the etiology of vascular dysfunction. Cardiac function
      parameters evaluated by echocardiography included stroke volume (SV), left
      ventricular end-diastolic volume (LVEDV), left ventricular fractional shortening
      (LVFS), ejection fraction (EF), cardiac output index (COI), heart rate (HR) and
      left ventricular posterior wall thickness (LVPWT). In addition, heart/body weight
      (heart/BW) ratios and systolic blood pressure were determined in normal hamsters
      and SCH. Our results indicated that systolic blood pressure increased 56% in SCH
      when compared to control animals (P<0.05). The increased blood pressure coexisted
      with normal COI, SV, LVEDV, LVPWT, LVFS, EF, HR and heart/BW ratios. NAD(P)H
      oxidase activity increased 77% in SCH compared to control animals (P<0.02). The
      increased oxidase activity was abolished by pre-treatment of animals with the
      angiotensin II type 1 receptor blocker losartan (25 mg/kg BW/day) for 10 days.
      Losartan also abolished the increased blood pressure observed at 2 months of age.
      The antioxidant N-acetylcysteine (NAC) abrogated the increased blood pressure
      when administered for 30 days to 1-month-old animals. Altogether, these findings
      suggest that the angiotensin II-dependent vascular abnormalities present in young
      cardiomyopathic hamsters are associated with oxidative stress and precede the
      echocardiographic abnormalities characteristic of heart failure.

PMID- 16301004
TI  - Transmission of respiratory rhythm: midline-crossing connections at the level of
      the phrenic motor nucleus?
AB  - We used three methods to test for the existence of transmission of respiratory
      rhythm across the midline at the level of the phrenic motor nucleus in rats using
      the in situ preparation over a range of ages from neonatal to juvenile. Stimulus
      triggered averages of phrenic activity for stimuli applied to one side of the
      spinal cord at C2 and C3 produced large peaks in the ipsilateral averages but no
      discernible peaks in the contralateral averages, unless the stimulating
      microelectrode was placed close to the midline in the ventral funiculus.
      Following mid-sagittal section of the medulla, respiratory rhythm was maintained
      for all ages, with bursts occurring on one phrenic nerve that were absent on the
      other. Cross-correlations of left and right phrenic discharges displayed peaks
      indicative of short time-scale synchronisation before the medullary transections
      but not afterwards. We therefore could not find evidence for transmission of
      respiratory rhythm across the midline at the phrenic motoneurone level; we did
      find evidence that that transmission via ipsilaterally descending axons of
      medullary phrenic pre-motor neurones is present at all ages.

PMID- 16301005
TI  - Multi residue screening of intact testosterone esters and boldenone undecylenate
      in bovine hair using liquid chromatography electrospray tandem mass spectrometry.
AB  - The abuse of esters of natural androgenic steroids in cattle fattening and sports
      is hard to control via routine urine testing. The esters are rapidly hydrolysed
      in vivo into substances which are also endogenously present in urine. In
      veterinary control strange findings of 17beta-testosterone and 17alpha
      testosterone in urine are often ignored because of the lack of statistically
      sound reference data of naturally occurring levels. An interesting alternative
      for inconclusive urine analyses in veterinary control can be provided by the
      analysis of the administered steroids themselves, i.e. the analysis of intact
      steroid esters in hair. Unfortunately, the analysis of intact steroid esters is
      complicated not only by the vulnerability of the esters which precludes alkaline
      hydrolysis of the hair, but also by the wide polarity range of short and long
      chain esters yielding very poor recoveries for either the one or the other. In
      this study, a multi-steroid esters LC/MS/MS screening method is presented for
      trace analysis of the synthetic intact esters of 17beta-testosterone and the
      undecylenate ester of 17beta-boldenone in bovine hair. The method, requiring only
      200 mg of pulverised hair, features a mild digestion procedure using tris(2
      carboxyethyl)phosphine hydrochloride (TCEP) and the use of four deuterium
      labelled steroid esters as internal standards covering the wide polarity range of
      the analytes. In spiked hair samples for most of the analytes the limit of
      detection and the accuracy using isotope dilution were 2-5 ng/g and 97-105%,
      respectively. The applicability was demonstrated using hair samples from a
      controlled experiment in which six bovines were injected intramuscularly with two
      different doses of two commercial mixtures of testosterone esters, and with two
      different doses of boldenone undecylenate. Depending on the dose all administered
      testosterone- and boldenone esters were found to be incorporated in bovine hair
      following a single intramuscular injection, except testosterone propionate which
      dose might have been too low.

PMID- 16301006
TI  - Simultaneous analysis of human plasma catecholamines by high-performance liquid
      chromatography with a reversed-phase triacontylsilyl silica column.
AB  - The clinical importance of simultaneous analysis of 3,4-dihydroxyphenylglycol
      with other human plasma catecholamines has been investigated to better understand
      the sympathetic nervous system. However, previous reports have had analytical
      difficulties with both resolution and extraction. The current study uses a
      reversed-phase triacontylsilyl silica (C30) column under the mobile phase
      condition without ion-pair reagents to separate catecholamines and their
      metabolites, with above 91% recoveries for intra-assay, above 85% for inter
      assay, and less than 10% (n=5) coefficient of variation. Lower detection limits
      (S/N=4) and quantification limits (S/N=6) were 40 and 100 pg/mL for
      norepinephrine, 3,4-dihydroxyphenylglycol, and 3,4-dihydroxyphenylalanine, 10 and
      20 pg/mL for epinephrine, 10 and 40 pg/mL for dopamine. Linear ranges were from
      40 to 5000 pg/mL for norepinephrine and 3,4-dihydroxyphenylalanine, from 100 to
      5000 pg/mL for 3,4-dihydroxyphenylglycol, and from 10 to 2000 pg/mL for
      epinephrine and dopamine. The C30 column may prove clinically useful, as it
      provides a convenient and simultaneous method of evaluation of human plasma
      catecholamines.

PMID- 16301007
TI  - Efficient high performance liquid chromatograph/ultraviolet method for
      determination of diclofenac and 4'-hydroxydiclofenac in rat serum.
AB  - A rapid and sensitive high-performance liquid chromatographic method was
      developed for determination of diclofenac and its major metabolite, 4'
      hydroxydiclofenac, in serum from rats treated with diclofenac. The method is
      simple with a one-step extraction procedure, isocratic HPLC separation, and UV
      detection at 280 nm. Use of N-phenylanthranilic acid as the internal standard
      provided good accuracy without interference by endogenous compounds or 5
      hydroxydiclofenac, another metabolite of interest. Limits of detection for
      diclofenac and 4'-hydroxydiclofenac were 0.0225 and 0.0112 microg/ml,
      respectively. Average extraction efficiencies of diclofenac, 4'
      hydroxydiclofenac, and the internal standard were >/=76%. The method was applied
      to serum collected at 3h after rats were treated with an experimentally useful
      dosage range of 3, 10 and 50mg/kg diclofenac. Recovery (as a percentage of dose)
      for the 4'-hydroxy metabolite in serum was found to consistently average from
      0.10 to 0.12% following each dosage, whereas recovery of diclofenac in serum
      declined from 0.45 to 0.37%. Thus, the method is suitable for measurement of a
      major diclofenac metabolite in experimental studies.

PMID- 16301008
TI  - Gastric bezoar creating a ball-valve effect.

PMID- 16301009
TI  - Chronic pancreatitis and quality of life.

PMID- 16301010
TI  - Short- and long-term therapeutic efficacy of nutritional therapy and
      corticosteroids in paediatric Crohn's disease.
AB  - BACKGROUND: Comparative data on the therapeutic efficacy of different enteral
      nutrition formulas and corticosteroids to obtain clinical remission and to induce
      mucosal healing influencing long-term disease course in paediatric Crohn's
      disease are still scarce. AIMS: To investigate the efficacy of nutritional
      therapy using three different formulas versus corticosteroids to achieve clinical
      remission as well as to induce intestinal mucosal healing in active Crohn's
      disease children. Duration of remission and effect on growth recovery were also
      assessed. PATIENTS AND METHODS: Clinical, laboratory, endoscopic and histological
      data of all new diagnosed active Crohn's disease paediatric cases were
      retrospectively recorded and reviewed. Thirty-seven children (median age 12.1
      years) received nutritional therapy (12 polymeric; 13 semi-elemental; 12
      elemental diet) and 10 subjects (median age 12.4 years) received corticosteroids.
      RESULTS: Similar clinical remission rate were observed after 8 weeks of
      treatment: 86.5% children receiving nutritional therapy versus 90% treated with
      corticosteroids. Improvement in mucosal inflammation occurred in 26 out of 37
      (64.8%) patients on nutritional therapy and in 4 out of 10 (40%) children on
      steroids (p < 0.05). Finally, seven subjects on nutritional therapy and none on
      corticosteroids achieved complete mucosal healing (p < 0.005) at the end of the
      treatment. Nutritional therapy was more effective than corticosteroids in
      improving nutritional status and linear growth recovery. Compared to
      corticosteroids, the duration of clinical remission was longer in the nutritional
      therapy groups without differences among the three different formulas.
      CONCLUSIONS: In children with active Crohn's disease, nutritional therapy is more
      effective than corticosteroids to improve intestinal inflammation and to maintain
      a more sustained clinical remission.

PMID- 16301011
TI  - The use of micro-CT to evaluate cortical bone geometry and strength in nude rats:
      correlation with mechanical testing, pQCT and DXA.
AB  - In both clinical and experimental settings, access to quantitative methods
      enabling the objective evaluation of cortical bone mass, structure, geometry and
      strength are essential for the assessment of efficacy and safety of different
      treatments aimed to improve bone strength. The ability of non-invasive
      methodologies (DXA, pQCT and micro-CT) to assess and quantify cortical bone mass
      and geometry was tested in a nude rat model in which bone loss was induced by
      surgical castration. Treatment with a bone antiresorptive (alendronate) or a bone
      forming (PTH) drug was used to: (A) validate the nude rat model in terms of bone
      metabolism, (B) test the ability of each technology to detect change in cortical
      bone geometry and (C) correlate cortical bone geometry with bone strength data
      obtained by 3-point bending method. Our observations regarding effect of
      castration and treatment with PTH and alendronate on cortical bone parameters in
      nude rats is in general agreement with previously published data obtained in
      immunocompetent male rats under similar experimental conditions. Data presented
      here support the hypothesis that nude rats have similar bone physiology and
      response to known bone therapies to that observed in normal rats and therefore
      could be effectively used to predict skeletal response in humans. All three
      technologies deployed in this study (DXA, pQCT and micro-CT) proved useful in
      describing cancellous and/or cortical bone parameters and positive correlations
      were demonstrated between data obtained by different methods. The cross-sectional
      area of a bone structure is crucial for resisting loads in bending or torsion and
      is described as "areal moment of inertia" for bending, and as "polar moment of
      inertia" in torsion. Novel, three-dimensional micro-CT methodology used in this
      study to assess geometry of cortical bone provides data that accurately describes
      cortical bone geometry and parallels cortical bone strength results obtained by
      the 3-point bending method. Our micro-CT data meet the criteria of providing
      quick, reproducible and accurate answers regarding cortical bone geometry as a
      predictor of cortical bone strength.

PMID- 16301012
TI  - Predicting bulimic symptoms: an interactive model of self-efficacy,
      perfectionism, and perceived weight status.
AB  - An interactive model of perfectionism, perceived weight status, and self-efficacy
      was tested on 406 women to predict the bulimic symptoms of binge eating and
      inappropriate compensatory behaviors separately. This longitudinal study assessed
      hypothesized vulnerabilities of high perfectionism and low self-efficacy and the
      stressor of feeling overweight at Time 1 and then gathered weekly assessments of
      binge eating, vomiting, laxative use, fasting, and diet pill use for 11 weeks. As
      predicted, results showed that perfectionism, weight perception, and self
      efficacy interacted to prospectively predict binge eating. In particular, women
      high in perfectionism who felt they were overweight and who had low self-efficacy
      reported the most number of weeks of binge eating. This interactive model did not
      predict inappropriate compensatory behaviors. Future directions and clinical
      implications are discussed.

PMID- 16301013
TI  - Reliability of the Eating Disorder Examination-Questionnaire in patients with
      binge eating disorder.
AB  - This study examined the test-retest reliability of the Eating Disorder
      Examination-Questionnaire (EDE-Q) in patients with binge eating disorder (BED).
      Short-term (mean days = 4.8; SD = 3.6) test-retest reliability of the EDE was
      examined in a sample of 86 patients with BED. Test-retest reliability was
      excellent for objective bulimic episodes (correlation = .84), but poor to
      unacceptable for subjective bulimic episodes and objective overeating episodes
      (correlations = .51 and .39, respectively). Test-retest reliabilities were good
      for the EDE-Q scales (correlations = .66 to .77), albeit somewhat variable for
      the individual EDE-Q items (.54 to .78). These findings support the reliability
      of the EDE-Q for patients with BED. The EDE-Q has utility for assessing the
      number of binge eating episodes (objective bulimic episodes) and associated
      features of eating disorders in patients with BED. The results for subjective
      bulimic episodes are consistent with previous studies in suggesting that these
      eating behaviors may not be reliable indicators of eating disorders for patients
      with BED.

PMID- 16301014
TI  - Eating Disorder Examination Questionnaire (EDE-Q): norms for young adult women.
AB  - In order to establish norms for the Eating Disorder Examination Questionnaire
      (EDE-Q) among young adult women, the questionnaire was administered to a large
      general population sample of women aged 18-42 yr in the Australian Capital
      Territory (ACT) region of Australia. Normative data were derived for EDE-Q
      subscales and for the occurrence of specific eating disorder behaviours, for each
      of five age bands (18-22, 23-27, 28-32, 33-37, 38-42 yr). Mean scores (SDs) for
      the Restraint, Eating Concern, Weight Concern and Shape Concern subscales for the
      total sample (n = 5,255) were, respectively, 1.30 (1.40), 0.76 (1.06), 1.79
      (1.51) and 2.23 (1.65). The mean global score was 1.52 (1.25). The regular
      occurrence of objective and subjective overeating episodes was reported by 10.6%
      and 12.7% of participants, respectively. The regular use of self-induced
      vomiting, laxative misuse, and use of diuretics, was reported by 1.4%, 1.0%, and
      0.3%, of participants, respectively, while 2.2% of participants reported
      regularly using diet pills. "Extreme dietary restraint" and "excessive exercise"
      were reported by 3.4% and 4.9% of participants, respectively. Both attitudinal
      and behavioural features of eating disorder psychopathology tended to decrease
      with increasing age. These data will inform researchers intending to use the EDE
      Q in epidemiological studies.

PMID- 16301015
TI  - Personal standards and evaluative concerns dimensions of "clinical"
      perfectionism: a reply to Shafran et al. (2002, 2003) and Hewitt et al. (2003).
AB  - Shafran, Cooper, and Fairburn (2002, 2003) provided a cognitive-behavioral
      analysis of "clinical" perfectionism, a construct they considered to involve both
      the determined pursuit of self-imposed standards and extremely vulnerable self
      evaluation. They argued against a multidimensional perspective to studying
      perfectionism. We respond to Shafran et al. (2002, 2003) and Hewitt, Flett,
      Besser, Sherry, and McGee's (2003) reply to Shafran et al. (2002) by considering
      the theoretical, empirical, and clinical implications of findings identifying two
      higher-order dimensions of perfectionism reflecting personal standards (PS) and
      self-critical evaluative concerns. Analyses of data from two diverse study
      groups, a college student sample (N = 527) and a clinical sample of patients with
      binge eating disorder (N = 236), revealed that self-criticism accounts for the
      relation between perfectionism measures and depressive, anxious, and eating
      disorder symptoms. We conclude that possessing high PS is not by itself
      maladaptive. Rather, self-critical evaluative tendencies are more relevant than
      PS to the critical processes Shafran et al. (2002) suggested contribute to the
      maintenance of clinical perfectionism.

PMID- 16301016
TI  - Responses to symptom induction exercises in panic disorder.
AB  - Exposure to panic symptoms (interoceptive exposure) is often included as part of
      treatment for panic disorder (PD), although little is known about the relative
      effects of particular symptom induction exercises. This study describes responses
      of individuals with PD and nonclinical controls to 13 standard symptom induction
      exercises and 3 control exercises. Generally, individuals with PD responded more
      strongly to symptom induction exercises than did controls. The exercises
      producing the most fear included spinning, hyperventilation, breathing through a
      straw, and using a tongue depressor. This study also reports findings regarding
      specific symptoms triggered by each exercise, the percentage of participants
      reporting fear during each exercise, and predictors of fear.

PMID- 16301017
TI  - A meta-analysis of psychological and pharmacological treatments for Body
      Dysmorphic Disorder.
AB  - Although psychological and pharmacological treatment approaches for Body
      Dysmorphic Disorder have been evaluated, the relative effectiveness of these two
      types of interventions has not been examined. We conducted a meta-analysis of
      randomized clinical trials and case series studies involving psychological (i.e.,
      behavioural, cognitive-behavioural, cognitive) or medication therapies. Our
      findings support the effectiveness of both types of therapy, but suggest that
      cognitive-behavioural treatment may be the most useful. These findings require
      cross-validation through large-scale clinical trials.

PMID- 16301018
TI  - Self-concept certainty in social phobia.
AB  - Two studies are reported which examined the content of beliefs about self
      attributes in social phobia, and the level of certainty with which these beliefs
      are held. The results of both studies indicated that individuals with social
      phobia held less positive beliefs about their personality characteristics in
      comparison to non-anxious individuals. In addition, social anxiety was associated
      with reduced subjective confidence in self-descriptiveness ratings for
      personality attributes (Study 1), as well as longer reaction times in making self
      descriptiveness decisions relative to general decisions about trait adjectives
      (Study 2). The association between social anxiety and reduced certainty in
      negative attribute ratings was evident after controlling for depression, general
      anxiety, stress, and the extent to which negative attributes were endorsed as
      being self-descriptive. Results are discussed in terms of the potential role that
      reduced self-concept certainty may play in social phobia.

PMID- 16301019
TI  - The structure of childhood obsessions and compulsions: dimensions in an
      outpatient sample.
AB  - While obsessive-compulsive disorder (OCD) is defined as a unitary condition,
      prior research has identified meaningful and distinct symptom dimensions in adult
      samples. In contrast, there have been no investigations of symptom dimensions in
      samples of children diagnosed with OCD. The present study sought to address this
      gap. Children diagnosed with OCD (n = 137) were administered the Children's Yale
      Brown Obsessive-Compulsive Scale symptom checklist and severity index. Symptoms
      were analyzed using principal components analysis. As with adult samples, four
      factors were identified from the checklist. However, these four factors
      (compulsions, sexual/aggressive obsessions, superstitions, and
      hoarding/ordering/somatic concerns) were different in content from adult studies.
      Further, several symptoms significantly contributed to more than one dimension.
      Each dimension was significantly correlated with scores from the severity index,
      with the exception of the obsession score with the hoarding/ordering/somatic
      concerns factor. Results suggest that there are distinct dimensions of symptoms
      in childhood OCD, but that these dimensions do not correspond to those identified
      in adults. Instead, it appears that some factors share variance, and the
      dimensions themselves are separated based upon developmental trajectories. The
      dimensions examined may be useful in future treatment studies using
      pharmacological and/or behavioral interventions.

PMID- 16301020
TI  - Accuracy of endoscopic optical coherence tomography in the detection of dysplasia
      in Barrett's esophagus: a prospective, double-blinded study.
AB  - BACKGROUND: Endoscopic optical coherence tomography (EOCT) is a high-resolution,
      cross-sectional tissue-imaging technique that provides microscopic morphologic
      information. EOCT should detect dysplasia in Barrett's epithelium, but this has
      not been established in a prospective blinded study. This study evaluated the
      accuracy of EOCT for the diagnosis and the exclusion of dysplasia in patients
      with Barrett's esophagus. METHODS: A 2.4-mm diameter EOCT probe was modified for
      use with a cap-fitted, two-channel endoscope. Pairs of EOCT image streams and
      jumbo biopsy specimens were obtained. Endoscopy/EOCT procedures were performed by
      4 endoscopists who separately reviewed the EOCT digital images for the absence or
      the presence of dysplasia (low grade, high grade, or cancer) for each biopsy
      specimen obtained. The endoscopists were blinded to the interpretation of the
      pathology. An experienced pathologist blinded to the endoscopic/EOCT findings
      evaluated each biopsy for the absence or the presence of dysplasia. The setting
      of the study was a major academic medical center. Adult patients with documented
      Barrett's esophagus greater than 2 cm were included in the study. The main
      outcome measurement was the accuracy of EOCT in the detection of dysplasia in
      patients with Barrett's esophagus. RESULTS: A total of 314 usable EOCT image
      stream/biopsy pairs were obtained in 33 patients. By using histology as the
      standard, the performance of EOCT was sensitivity, 68%; specificity, 82%;
      positive predictive value, 53%; negative predictive value, 89%; and diagnostic
      accuracy, 78%. Diagnostic accuracy for the 4 endoscopists ranged from 56% to 98%.
      Limitations of the study were the variability in endoscopists' accuracy rates,
      difficulty in real-time interpretation, and the need for refined criteria of
      dysplasia by EOCT imaging. CONCLUSIONS: The current EOCT system has an accuracy
      of 78% for the detection of dysplasia in patients with Barrett's esophagus. EOCT
      could be used to target biopsies to areas of Barrett's epithelium with a higher
      probability for the presence of dysplasia. However, further modifications,
      including increased resolution and identification of further potential OCT
      characteristics of dysplasia, are needed before EOCT can be used clinically.

PMID- 16301021
TI  - Optical coherence tomography and the detection of dysplasia in Barrett's
      esophagus.

PMID- 16301022
TI  - Patients with functional heartburn are more likely to report retrosternal
      discomfort during wireless pH monitoring.
AB  - BACKGROUND: Although the wireless Bravo pH system is effective, some patients
      experience retrosternal sensations possibly caused by esophageal sensitivity that
      may complicate clinical application. METHODS: Ambulatory pH of 40 consecutive
      patients with GERD who had erosive esophagitis or nonerosive reflux disease, were
      monitored for 2 days with the Bravo system. Results were stratified and compared
      on the basis of self-awareness of the intraesophageal capsule. RESULTS:
      Pathologic acid reflux was diagnosed in 20 patients and normal reflux was
      diagnosed in 20 patients. Seventeen patients (42.5%) reported retrosternal
      discomfort, and 12 of them (70.6%) had normal reflux. Patients with retrosternal
      discomfort were less likely to have moderate endoscopic esophagitis, i.e., Los
      Angeles classification grades B, C, and D endoscopic esophagitis (p = 0.006), and
      were less likely to have significantly elevated esophageal acid exposure (p =
      0.0036) than those who did not perceive the discomfort. Reported discomfort was
      not associated with age, gender, or the presence of endoscopic esophagitis.
      CONCLUSIONS: The negative correlation between Bravo-capsule-induced retrosternal
      discomfort and esophageal-acid exposure indicates modified mechanical afferent
      nerve function after long-term acid stimulation. Capsule-induced retrosternal
      discomfort in the presence of normal acid exposure suggests functional heartburn.

PMID- 16301023
TI  - Cryoablation of Barrett's esophagus: a pilot study.
AB  - BACKGROUND: Numerous ablative modalities have demonstrated varying degrees of
      efficacy in the eradication of Barrett's esophagus (BE). However, they are
      associated with either high cost, patient discomfort, complications, tedious
      application, residual underlying BE, or some combination of the above. The aim of
      this study was to evaluate the safety and the efficacy of a new cryogenic device
      by using liquid nitrogen sprayed through an open tipped cryogenic catheter placed
      through the accessory channel of an upper endoscope. METHODS: A prospective,
      single center study was performed on patients with a long-standing history of BE
      followed in a Barrett's registry. Patients with degrees of dysplasia ranging from
      none to multifocal high-grade dysplasia were treated. All patients were treated
      with 40 mg rabeprazole 3 times per day during the treatment period. Elimination
      of acid reflux was confirmed via 24-hour esophageal pH studies. Cryoablation was
      applied hemicircumferentially to 4-cm-long segments at monthly intervals, until
      the entire segment of BE was eliminated. RESULTS: Eleven patients were treated.
      There was reversal of BE in all patients. In 9 of 11 (78%) patients who completed
      the protocol, there was complete endoscopic and histologic reversal of BE. There
      was no subsquamous specialized intestinal metaplasia at the 6-month follow-up. No
      complications occurred. CONCLUSIONS: Based on preliminary results, low-pressure
      spray cryoablation of BE under direct endoscopic visualization is safe and easy
      to perform. Its relative lack of patient discomfort and its simplicity and
      demonstrated efficacy make it a modality that should be further explored in the
      ablation of GI mucosal lesions such as BE and perhaps early esophageal cancer.

PMID- 16301024
TI  - Can deep freezing join the endoscopic Barrett's mucosal ablation party? Cautious
      optimism is warranted.

PMID- 16301025
TI  - The effect of GI bleeding on Helicobacter pylori diagnostic testing: a
      prospective study at the time of bleeding and 1 month later.
AB  - BACKGROUND: Some case series and cohort studies suggest that acute GI bleeding
      decreases the sensitivity of Helicobacter pylori diagnostic testing. OBJECTIVE:
      To assess H pylori biopsy testing in patients with acute upper-GI bleeding and 1
      month later. DESIGN: Prospective cohort study using patients as their own
      controls. SETTING: Urban county hospital. PATIENTS: Sixty-one patients with acute
      variceal bleeding. INTERVENTIONS: Antral and body endoscopic biopsies at
      admission and 1 month later. MAIN OUTCOME MEASUREMENTS: CLOtest and histologic
      examinations were performed and biopsy specimens were coded and mixed for blinded
      histologic examination for H pylori density and inflammation. RESULTS: CLOtest
      results changed from H pylori negative at baseline to H pylori positive at 1
      month in two patients (3%), from H pylori positive to H pylori negative in 6
      patients (10%), and remained the same in 53 (87%). Histologic results changed
      from H pylori negative at baseline to H pylori positive at 1 month in two
      patients (3%), from H pylori positive to H pylori negative in 5 patients (8%),
      and remained the same in 54 (89%). Changes occurred only in patients with low H
      pylori density. No significant increase in H pylori density or change in
      inflammatory cell infiltration was seen. CLOtest sensitivity was 8% higher with
      bleeding vs. 1 month after bleeding (79% vs. 71%; 95% CI of difference was -11%
      to 27%; i.e., maximal potential decrease in sensitivity with bleeding is 11%).
      LIMITATIONS: The population is not one for which H pylori testing is recommended,
      and biopsy test performance was less consistent than expected. CONCLUSIONS: Acute
      GI bleeding did not decrease the sensitivity of rapid urease testing, unless the
      effect lasts more than 1 month. Furthermore, bleeding did not produce falsely
      negative histologic examinations for H pylori, decrease H pylori density, or
      alter inflammatory cell infiltration. However, given the lower than expected
      overall CLOtest sensitivity and frequent use of proton pump inhibitors for GI
      bleeding, histology may be preferred in this setting.

PMID- 16301026
TI  - The learning curve for EMR with circumferential mucosal incision in treating
      intramucosal gastric neoplasm.
AB  - BACKGROUND: EMR with circumferential mucosal incision facilitates en bloc
      resection, which is the most important predictor for complete resection in the
      treatment of intramucosal gastric neoplasm. The objective of the study was to
      evaluate the efficacy and the safety of EMR with circumferential mucosal incision
      in relation to the endoscopist's experience. METHODS: In this retrospective
      study, we analyzed the outcome of 80 EMR procedures performed by a single
      endoscopist at the National Cancer Center, Goyang, Korea. The EMR procedure with
      circumferential mucosal incision was performed with a conventional needle knife.
      We compared the en bloc resection rate, the complete resection rate, the duration
      of the procedure time, and the associated complications by quartiles. RESULTS:
      From the first to the last quartile, en bloc resection rates were 55%, 45%, 85%,
      and 85% (p = 0.006), and complete resection rates were 65%, 60%, 90%, and 85% (p
      = 0.039). The increase in the mean en bloc and complete resection rates between
      the first two quartiles and the second two quartiles was significant (p = 0.002
      and p = 0.019, respectively). Three perforations (15%) were reported in the first
      quartile and only one (1.7%) in the remaining 3 quartiles (p = 0.046). The
      procedure time also decreased after the first 20 cases (p = 0.004). CONCLUSIONS:
      For an experienced endoscopist, EMR with circumferential mucosal incision could
      be performed effectively and safely after the experience of 40 cases.

PMID- 16301027
TI  - A learning curve for advanced endoscopic resection.

PMID- 16301028
TI  - Treatment of early gastric cancer in the elderly patient: results of EMR and
      gastrectomy at a national referral center in Japan.
AB  - BACKGROUND: The Japanese population is rapidly aging, and the actual number of
      elderly patients with gastric cancer, including early cancer, has been
      increasing, even though the standardized incidence of gastric cancer in the
      population is decreasing. The optimal treatment for these patients remains a
      challenge to the surgeon. The aim of this retrospective analysis was to describe
      the results of gastrectomy and EMR for early gastric cancer in elderly patients
      (80 years of age and over). METHODS: This is a retrospective review of 93 elderly
      patients who had undergone gastrectomy or EMR at the National Cancer Center
      Hospital for early gastric cancer. EMR was performed aiming en bloc local
      resection with a clear curative margin (R0). The clinicopathologic
      characteristics, comorbidity, postoperative mortality, and outcome were recorded.
      RESULTS: Gastrectomy was performed in 44 patients (surgery group) and EMR in 49
      patients (EMR group). There were significant differences in mean tumor size (p <
      0.05), histologic type (p < 0.05), and depth of tumor invasion (p < 0.05) between
      the two groups. There was no significant difference in comorbidity between the
      two groups. No operative death was reported in either group. In the EMR group, 7
      patients were reported to have recurrence of local disease and two patients died
      of advanced disease. There were no significant differences in the overall 3-year
      survival rate or the 5-year survival rate between the surgery group and EMR group
      (73.5% vs. 82.5% and 55.0% vs. 62.5%, respectively). CONCLUSIONS: EMR (R0)
      resection was performed safely in the elderly, and the overall results were
      excellent, the same as the results with gastrectomy. Gastrectomy can still be
      performed if EMR is unsuccessful.

PMID- 16301029
TI  - Treatment of early gastric cancer in the elderly: leave it, cut out, peel out?

PMID- 16301030
TI  - Utilization of colonoscopy in the United States: results from a national
      consortium.
AB  - BACKGROUND: To assess capacity for colonoscopy, we need to understand current
      utilization of colonoscopy in diverse clinical practice settings. The objective
      of this study was to determine the utilization of colonoscopy in diverse clinical
      practice settings. METHODS: The Clinical Outcomes Research Initiative (CORI) data
      repository, which receives endoscopy reports from 73 diverse adult practice sites
      in the United States was used. Colonoscopy reports from January 2000 to August
      2002 were analyzed to determine the demographic characteristics of adult patients
      who received a colonoscopy and the procedure indication. The relationship of age,
      race, gender, and procedure indication was analyzed. RESULTS: Results of
      colonoscopies in 146,457 unique patients were analyzed. Of the reports, 68% came
      from nonacademic settings. Patients less than 50 years of age accounted for 20%
      of colonoscopies. The most common indications were rectal bleeding (33.6%),
      irritable bowel symptoms (23.8%), or screening because of a positive family
      history of colorectal cancer (22.4%) and screening with a primary colonoscopy or
      a fecal occult blood test (FOBT) (12.8%). In patients 50 years and older,
      asymptomatic screening (average-risk screening colonoscopy, positive family
      history, or FOBT positivity) accounted for 38.1% of all colonoscopies.
      Surveillance colonoscopy in patients with previous cancer or polyps accounted for
      21.9% of colonoscopies performed in this age group. Differences in utilization
      were noted, based on gender and race. CONCLUSIONS: Colonoscopy utilization varies
      based on age, gender, and race. Colonoscopy often is performed in patients less
      than 50 years old for irritable bowel symptoms; rectal bleeding; or average-risk
      screening, for which benefits are uncertain. In patients older than 50 years,
      surveillance after polyp removal is a common indication and may be overused.
      Understanding utilization can lead to further study to determine outcomes, to
      optimize utilization, and to provide a basis for shifting limited resources.

PMID- 16301031
TI  - Meeting the challenge of colorectal cancer screening.

PMID- 16301032
TI  - Sporadic colonic hamartomas in adults: a retrospective study.
AB  - BACKGROUND: Colonic hamartomas are uncommon in adults. The aims of this study
      were to determine (1) the prevalence of colonic hamartomas in an adult population
      undergoing colonoscopy and (2) the clinical, endoscopic, and histologic features
      of colonic hamartomas in adult patients. METHODS: A pathology database identified
      19 adult patients of 12,707 patients with colonic hamartomas in the 11-year study
      period from January 1992 to October 2002. An endoscopic computer database
      provided information about the number of colonoscopies performed and the presence
      or the absence of colonic polyp(s) in study patients. Charts of patients with
      colonic hamartomas were reviewed, and clinical and demographic data were
      collated. RESULTS: Nineteen patients were found to have colonic hamartomas. The
      mean age of these patients was 55 years, with an age distribution ranging from 25
      to 81 years. The prevalence of colonic hamartomas in this study population was
      0.15%. The prevalence of hamartomas in patients with colon polyps at index
      colonoscopy was 0.073%. Colonic hamartomas were more common in men than in women.
      The indication for colonoscopy for the majority (68%) of patients was
      hematochezia or the presence of occult blood in the stool. Three fourths of the
      polyps were greater than 1 cm in diameter, and 89% were pedunculated. Two thirds
      of the hamartomatous polyps were localized to the rectosigmoid region. Endoscopic
      characteristics of hamartomas were indistinguishable from adenomas. CONCLUSIONS:
      Colonic hamartomas in adults are rare. They tend to be single, pedunculated, and
      localized predominantly in the rectosigmoid region. Endoscopic resection of
      colonic hamartomas was successful in all patients.

PMID- 16301033
TI  - Is a negative colonoscopy associated with reassurance or improved health-related
      quality of life in irritable bowel syndrome?
AB  - BACKGROUND: Although colonoscopy is rarely of clinical use in irritable bowel
      syndrome (IBS), it is, nonetheless, frequently performed in IBS. Proponents
      contend that a normal colonoscopy provides reassurance and improves health
      related quality of life (HRQOL). However, no previous data have measured these
      effects. We sought to measure the association of a normal colonoscopy with
      reassurance and HRQOL in patients with IBS aged <50 years. METHODS: We
      retrospectively evaluated 458 patients with IBS, aged 18 to 49 years. Subjects
      completed a symptom questionnaire, the Symptom Checklist 90 (SCL-90) psychometric
      checklist, and the Short Form 36 (SF-36) Health Survey. The main outcomes were
      HRQOL as measured by the mental component score (MCS) and the physical component
      score (PCS) of the SF-36 and reassurance as operationalized by a negative
      response to the question: "Do you think there is something seriously wrong with
      your body?" The independent variable was presence or absence of a previous normal
      colonoscopy. We performed regression analysis to control for potential
      confounders, including timing of colonoscopy. RESULTS: The unadjusted mean SF-36
      PCS was 42 +/- 10 (0-100 scale: 0, worst) in patients with recent colonoscopy
      (<12 months), 45 +/- 11 in patients with distant colonoscopy (>12 months), and 45
      +/- 10 in patients without colonoscopy (p = 0.78). The mean SF-36 MCS in the 3
      groups were 42 +/- 13, 44 +/- 11, and 43 +/- 11 (p = 0.57). Colonoscopy did not
      impact the proportion reassured (69.3%, 67.2%, 66.6%; p = 0.85). There were no
      significant differences between groups for any outcomes when adjusting for
      potential confounders. CONCLUSIONS: We found no independent association between a
      negative colonoscopy and reassurance or improved HRQOL in IBS patients aged <50
      years. These results suggest that the role of colonoscopy in IBS may be limited
      but require confirmation in prospective trials.

PMID- 16301034
TI  - Colonoscopy in irritable bowel syndrome: whom are we reassuring?

PMID- 16301035
TI  - Endoscopic removal of malfunctioning biliary self-expandable metallic stents.
AB  - BACKGROUND: Endoscopic removal of malfunctioning self-expandable metallic biliary
      stents (SEMS) is difficult and not well described. The aim of this study is to
      review the indications, the techniques, and the results of SEMS removal in a
      cohort of patients with malfunctioning stents. METHODS: All patients who
      underwent an attempt at endoscopic removal of biliary SEMS over a 5-year period
      were retrospectively identified. The main indications for SEMS removal were the
      following: distal migration of the stent or impaction to the duodenum, impaction
      into the bile-duct wall, tissue ingrowth, and inappropriate length of the stent
      causing occlusion of intrahepatic ducts. SEMS were removed by using foreign-body
      forceps or polypectomy snares. RESULTS: Endoscopic removal of 39 SEMS (13
      uncovered and 26 covered) was attempted in 29 patients (17 men; mean age, 66
      years). SEMS extraction was attempted after a mean of 7.5 months (8.75 months
      standard deviation) post-SEMS insertion. Removal was successful in 20 patients
      (68.9%) and in 29 SEMS (74.3%). Covered SEMS were effectively removed more
      frequently than uncovered ones: 24 of 26 (92.3%) and 5 of 13 (38.4%),
      respectively (p < 0.05). No major complications were recorded. Multivariate
      analysis showed that the time interval between insertion and removal, SEMS
      length, stent-mesh design (zigzag vs. interlaced), and indication for removal
      were not predictive of success at stent removal. CONCLUSIONS: Endoscopic removal
      of biliary SEMS is feasible and safe in more than 70% of cases. Because only 38%
      of uncovered SEMS were removable, the presence of a stent covering is the only
      factor predictive of successful stent extraction. The presence of diffuse and
      severe ingrowth was the main feature limiting SEMS removal.

PMID- 16301036
TI  - SEMS removal: salvage technique or new paradigms.

PMID- 16301037
TI  - EUS training and practice patterns among gastroenterologists completing training
      since 1993.
AB  - BACKGROUND: EUS training and practice patterns vary widely. The aim of this study
      was to assess EUS training methods, volumes, and practice patterns, and to obtain
      subjective assessment of endoscopic competence from endosonographers. METHODS: A
      survey was sent to over 1400 U.S. and international gastroenterologists who
      completed training since 1993. We assessed demographics, whether EUS is
      performed, how EUS training was obtained, and volume and type of EUS procedures
      performed in training and at present. Subjective assessment of adequacy of
      training was also obtained. RESULTS: A total of 157 physicians responded,
      including 76 EUS performers, of whom 67% completed advanced endoscopy fellowship,
      14% were EUS trained during GI fellowship, and 19% learned via other means. EUS
      performers were subgrouped into those who had and had not completed advanced
      endoscopy fellowship, and those within and outside of an academic practice. There
      were significant associations between the number of upper EUS,
      pancreaticobiliary, and EUS-guided FNAs performed during training (p < 0.001 for
      all 3 groups) and completion of advanced endoscopy fellowship. Physicians in
      academic practice performed more EUS and FNAs per month than physicians in other
      types of practice (p values <0.001 and 0.001, respectively); 93.3% of respondents
      felt they received adequate instruction in diagnostic EUS, regardless of type of
      training; 88.9% of EUS performers felt they received adequate instruction in
      performing FNA. CONCLUSIONS: Most EUS performers are in academic practice. Those
      with advanced training obtained higher training volumes and perform higher
      volumes of EUS. The majority of respondents felt well trained regardless of
      training type and the number of procedures performed during training. This is the
      first analysis to assess these aspects of EUS training and practice.

PMID- 16301038
TI  - Efficacy and costs of a one-day hands-on EASIE endoscopy simulator train-the
      trainer workshop.
AB  - BACKGROUND: The efficacy of an intensive hands-on training in endoscopic
      hemostasis on the compactEASIE simulator has been previously demonstrated in a
      randomized prospective trial. In the current study, we evaluated how quickly and
      effectively new tutors, without simulator training experience, are able to
      acquire teaching skills in endoscopic hemostasis. METHODS: Five tutors with prior
      Erlangen Active Simulator for Interventional Endoscopy (EASIE) teaching
      experience instructed 7 endoscopists without prior EASIE experience on how to
      teach when using the model. These new tutors then independently conducted a
      workshop for 8 fellows in 4 hemostasis techniques. Results were compared with a
      historical control trained similarly by experienced tutors. Two one-day workshops
      in endoscopic hemostasis on the compactEASIE ex vivo endoscopy simulator were
      conducted in a category A hospital in New York City, New York. Skill scores at
      the end of training were compared with baseline skills assessments, and
      qualitative ratings of the new tutors were obtained from both the trainees and
      the experienced tutors. RESULTS: Significant improvement was achieved by the
      fellows in all 4 skills areas. Both the expert tutors and the trainees
      consistently rated the teaching skill of the new tutors highly. Fellows' skill
      acquisition using new tutors was of similar magnitude to that achieved in the
      prior EASIE trial using experienced trainers teaching the fellows. CONCLUSIONS:
      It is feasible to conduct an effective EASIE train-the-trainer course in one day.
      Tutors trained in this manner are able to provide a similar educational
      experience with objective improvement in trainee skill to experts who have
      conducted many hands-on workshops.

PMID- 16301039
TI  - Validation of low-temperature steam with formaldehyde sterilization for
      endoscopes, using validation device.
AB  - BACKGROUND: Validation of sterilization is an important step before clinical use
      of medical equipment. Adequate validation of sterilization of the endoscope has
      not been reported. One reason for this is the lack of suitable devices for
      validation. METHODS: The VDES (validation device for endoscope sterilization;
      Olympus prototype model, Olympus, Tokyo, Japan) was designed in two types (type A
      and type B) and resembles gastroscopes and duodenoscopes, respectively. Each type
      consists of inner and outer tubing and a central capsule containing a biological
      indicator. The device was designed to examine the effectiveness of low
      temperature sterilizers, such as ethylene oxide gas, hydrogen peroxide gas
      plasma, and low-temperature steam with formaldehyde (LTSF) sterilizer. The aim of
      this study was to validate the sterilization of GI endoscopes by the LTSF
      sterilizer. Sterilization was assessed using both types of VDES after a 60-min
      application of LTSF. RESULTS: Culture of the biological indicator confirmed the
      complete eradication of the bacteria in a total of 10 experiments with each type
      of VDES after LTSF sterilization. CONCLUSIONS: Our results confirm that the LTSF
      sterilizer may sterilize endoscopes currently distributed by Olympus.
      Commercialization of VDES will make it possible to evaluate the reliability of
      sterilization when it is set in the sterilization device with endoscopes.

PMID- 16301040
TI  - Tissue damage of different submucosal injection solutions for EMR.
AB  - BACKGROUND: When choosing submucosal injection solutions for EMR, tissue damage
      should be considered, as well as the lesion-lifting ability. The objective of the
      study was to find out the potential tissue damage of submucosal injection
      solutions. METHODS: The submucosal injection solutions examined were the
      following: normal saline solution (NS), 3.75% NaCl, 20% and 50% dextrose water
      (DW), a glycerin solution (Glyceol; 10% glycerin with 0.9% NaCl plus 5%
      fructose), and two hyaluronic acid (HA) solutions (0.25% 1900 kDa/NS solution and
      0.125% 1900 kDa/ Glyceol solution). Furthermore, DW with different concentrations
      (5%, 10%, 15%, 30%, 40%) also was examined to find out the tolerable
      concentration without tissue damage. A total of 2 mL of each solution per stomach
      were injected by endoscopy into the submucosal layer at the separate sites of 4
      living minipigs. Two minipigs were euthanized after 30 minutes of endoscopic
      observations, and the others were euthanized after additional endoscopic
      observations a week after injection. RESULTS: There was no apparent tissue damage
      in NS, 5% and 10% DW, Glyceol, or two solutions of HA, whereas, hypertonic
      solutions, except Glyceol and 10% DW, have more or less potency of tissue damage.
      In 3.75% NaCl and DW with concentrations of >or=20%, considerable tissue damage
      was observed, which might affect resected EMR specimens and ulcer healing.
      CONCLUSIONS: Use of hypertonic solutions except Glyceol is not recommended with
      respect to tissue damage. A combination of HA and Glyceol is the most favorable
      submucosal injection solution, considering tissue damage and lesion-lifting
      ability.

PMID- 16301041
TI  - Submucosal injection: safety cushion at what cost?

PMID- 16301042
TI  - Compensation philosophies.

PMID- 16301043
TI  - Ethical and medicolegal aspects of PEG-tube placement and provision of artificial
      nutritional therapy.

PMID- 16301044
TI  - Reevaluating PEG tube placement in advanced illness.

PMID- 16301045
TI  - The study of dynamic chemical magnifying endoscopy in gastric neoplasia.
AB  - BACKGROUND: We assessed the usefulness of acetic acid-enhanced magnifying
      endoscopy in the diagnosis of gastric neoplasia. METHODS: Forty-five patients (27
      men, 18 women; median age 61.6 years) with gastric carcinoma or adenoma were
      enrolled in a prospective trial of enhanced magnifying endoscopy after
      instillation of 1.5% acetic acid. Acetic acid-enhanced magnified views of
      carcinoma or adenoma and the surrounding non-neoplastic mucosa were observed, and
      the duration of whitening time of each lesion was recorded. OBSERVATIONS:
      Magnified views of carcinoma showed a minute, grain-like pattern that differed
      from the surrounding noncancerous mucosa. The histopathologic diagnostic criteria
      were based on the Vienna classification of GI epithelial neoplasia. The mean
      duration of whitening differed with each histologic type: low-grade adenoma, 94
      seconds; high-grade adenoma, 24.3 seconds; noninvasive carcinoma, 20.1 seconds;
      invasive intramucosal carcinoma, 3.5 seconds; and submucosal carcinoma or beyond,
      2.5 seconds. The duration in the non-neoplastic surrounding mucosa was 90
      seconds. After the disappearance of whitening in the carcinoma, the irregular
      pattern of the carcinoma reappeared, and the contrast between carcinomatous
      microvessels and the whitened non-neoplastic tissue became very clear on
      magnifying endoscopy. In accordance with the duration of whitening, more than 1
      minute was termed "continuous whitening," from 31 to 60 seconds was "delayed
      disappearance of whitening," from 30 to 6 seconds was "early disappearance of
      whitening," and 0 to 5 seconds was "no response." CONCLUSIONS: Acetic acid
      enhanced magnifying endoscopy was useful for the diagnosis of gastric
      adenocarcinoma. The duration of whitening differed among grades of neoplasia, and
      it was possible to observe changes in the whitening with time. Acetic acid
      enhanced magnifying endoscopy, therefore, can be termed "dynamic chemical
      magnifying endoscopy."

PMID- 16301046
TI  - In vivo optical coherence tomography imaging of the pancreatic and biliary ductal
      system.
AB  - BACKGROUND: In vivo optical coherence tomography (OCT) imaging has not yet been
      applied to the pancreatic ductal system. The aim of this study was to obtain in
      vivo OCT images of dog pancreatic and biliary ducts, and to correlate the images
      with histology. METHODS: Images of dog pancreatic and biliary ducts were obtained
      by using an in vivo OCT probe introduced through the respective papillary
      orifices. Each duct was imaged in multiple locations, and the site of imaging was
      marked with injected India ink. After imaging, the dogs were euthanized, and the
      pancreaticobiliary system was harvested. Histologic cross sections were
      correlated with in vivo OCT images by measuring the structures seen on in vivo
      OCT images and correlating them with structures seen on corresponding histology
      slides that contained India ink. OBSERVATIONS: Eighteen pairs of in vivo OCT
      images and histology slides from the bile duct and the pancreatic duct were
      obtained from 5 dogs. The entire duct wall could be visualized. A low reflective
      in vivo OCT layer corresponding to the epithelium could be discerned on many
      images. The bile duct showed a more complex architecture and had greater
      variations within the reflective OCT layers, possibly because of greater
      cellularity within the lamina propria. Nuclei within cells could not be
      identified, and structures adjacent to the ducts could not be imaged.
      CONCLUSIONS: In vivo OCT is capable of imaging the pancreaticobiliary ductal
      system and of identifying the epithelial layer. Because of limited depth of
      imaging (320-845 micron), OCT is unlikely to serve the purpose of tumor staging.

PMID- 16301047
TI  - Simultaneous decompression colonoscopy and radiologic G-tube insertion in a
      patient with megacolon because of chronic colonic pseudo-obstruction.

PMID- 16301048
TI  - Rectal carcinoid tumor mimicking colonic adenomatous lesion.

PMID- 16301049
TI  - Liesegang rings: EUS appearance and FNA cytomorphology of a perirenal cyst.

PMID- 16301050
TI  - Rectal endometriosis.

PMID- 16301051
TI  - Mediastinitis after EUS-guided FNA biopsy of a posterior mediastinal metastatic
      teratoma.

PMID- 16301052
TI  - Rapid alternating recorder exchange in capsule endoscopy allows early detection
      of bleeding source in acute GI bleeding of obscure origin.

PMID- 16301053
TI  - Intestinal pseudo-obstruction as the initial presentation of systemic lupus
      erythematosus: the need for enteroscopic evaluation.

PMID- 16301054
TI  - Balloon-assisted intubation of the ileocecal valve to facilitate retrograde
      double-balloon enteroscopy.

PMID- 16301055
TI  - Endoloop ligation of a large colonic lipoma: a novel technique.

PMID- 16301056
TI  - Endoscopic placement of video capsule in a pediatric population.

PMID- 16301057
TI  - Endoscopic mucosal resection for lateral spreading tumors of the colorectum:
      further randomized studies are required.

PMID- 16301060
TI  - Because they can.

PMID- 16301062
TI  - Double-balloon enteroscopy for the detection of midgut carcinoids.

PMID- 16301064
TI  - Management of primary early gastric cancers.

PMID- 16301065
TI  - Application of multivariate curve resolution methods to on-flow LC-NMR.
AB  - The application of evolving window factor analysis (EFA), subwindow factor
      analysis (SFA), iterative target transformation factor analysis (ITTFA),
      alternating least squares (ALS), Gentle, automatic window factor analysis
      (AUTOWFA) and constrained key variable regression (CKVR) to resolve on-flow LC
      NMR data of eight compounds into individual concentration and spectral profiles
      is described. CKVR has been reviewed critically and modifications are suggested
      to obtain improved results. A comparison is made between three single variable
      selection methods namely, orthogonal projection approach (OPA), simple-to-use
      interactive self-modelling mixture analysis approach (SIMPLISMA) and simplified
      Borgen method (SBM). It is demonstrated that LC-NMR data can be resolved if NMR
      peak cluster information is utilised.

PMID- 16301066
TI  - A virtual-modeling and multivariate-optimization examination of HPLC parameter
      interactions and opportunities for saving analysis time.
AB  - The interrelations of parameters in HPLC are very complicated, even in a simple
      problem. Optimization requires considering all the adjustable parameters in
      concert, but the amount of work required to do this experimentally is
      prohibitive. However, if we first choose the selectivity parameters, we can then
      successfully and rapidly perform a multivariate optimization of the efficiency
      parameters within a numerical model. By examining this process with a level of
      detail not normally necessary in routine work, we reveal the complexity of
      parameter interactions in a simple separation, and the potential for large
      savings of analysis time by properly balancing parameter values. We show how to
      reduce a 13 min experimental separation to less than 2 min without utilizing
      ultra-small particles or pressure beyond the capabilities of an ordinary HPLC
      instrument. Ultra-small particles will often improve analysis times when the
      separation is plate-number-limited, but if the particles are smaller than optimal
      for the required separation, then larger particles will require less analysis
      time.

PMID- 16301067
TI  - Probability theory for number of mixture components resolved by n independent
      columns.
AB  - A general theory is proposed for the probability of different outcomes of success
      and failure of component resolution, when complex mixtures are partially
      separated by n independent columns. Such a separation is called an n-column
      separation. An outcome of particular interest is component resolution by at least
      one column. Its probability is identified with the probability of component
      resolution by a single column, thereby defining the effective saturation of the n
      column separation. Several trends are deduced from limiting expressions of the
      effective saturation. In particular, at low saturation the probability that
      components cluster together as unresolved peaks decreases exponentially with the
      number of columns, and the probability that components cluster together on
      addition of another column decreases by a factor equal to twice the column
      saturation. The probabilities of component resolution by n-column and two
      dimensional separations also are compared. The theory is applied by interpreting
      three sets of previously reported retention indices of the 209 polychlorinated
      biphenyls (PCBs), as determined by GC. The origin of column independence is
      investigated from two perspectives. First, it is suggested that independence
      exists when the difference between indices of the same compound on two columns is
      much larger than the interval between indices required for separation. Second, it
      is suggested that independence exists when the smaller of the two intervals
      between a compound and its adjacent neighbors is not correlated with its
      counterpart on another column.

PMID- 16301068
TI  - The chemometric resolution and quantification of overlapped peaks form
      comprehensive two-dimensional liquid chromatography.
AB  - The chemometric resolution and quantification of overlapped peaks from
      comprehensive two-dimensional (2D) liquid chromatography (LCxLC) data are
      demonstrated. The LCxLC data is produced from an in-house LCxLC analyzer that
      couples an anion-exchange column via a multi-port valve with a reversed-phase
      column connected to a UV absorbance detector. Three test mixtures, each
      containing a target analyte, are subjected to partial LCxLC separations to
      simulate likely cases of signal overlap. The resulting unresolved target-analyte
      signals are then analyzed by the standard-addition method and two chemometric
      methods. The LCxLC analyses of a test mixture and its corresponding standard
      addition mixture results in two data matrices, one for each mixture. The stacking
      of these two data matrices produces a data structure that can then be analyzed by
      trilinear chemometric methods. One method, the generalized rank annihilation
      method (GRAM), uses a non-iterative eigenvalue-based approach to mathematically
      resolve overlapped trilinear signals. The other method, parallel factor analysis
      (PARAFAC), uses an iterative approach to resolve trilinear signals by the
      optimization of initial estimates using alternating least squares and signal
      constraints. In this paper, GRAM followed by PARAFAC analysis is shown to produce
      better qualitative and quantitative results than using each method separately.
      For instance, for all three test mixtures, the GRAM-PARAFAC approach improved
      quantitative accuracy by at least a factor of 4 and quantitative precision by
      more than 2 when compared to GRAM alone. This paper also introduces a new means
      of correcting run-to-run retention time shifts in comprehensive 2D
      chromatographic data.

PMID- 16301069
TI  - Optimisation of high performance liquid chromatography separation of
      neuroprotective peptides. Fractional experimental designs combined with
      artificial neural networks.
AB  - The study of experimental design conjunction with artificial neural networks for
      optimisation of isocratic ion-pair reverse phase HPLC separation of
      neuroprotective peptides is reported. Different types of experimental designs
      (full-factorial, fractional) were studied as suitable input and output data
      sources for ANN training and examined on mixtures of humanin derivatives. The
      independent input variables were: composition of mobile phase, including its pH,
      and column temperature. In case of a simple mixture of two peptides, the
      retention time of the most retentive component and resolution were used as the
      dependent variables (outputs). In case of a complex mixture with unknown number
      of components, number of peaks, sum of resolutions and retention time of ultimate
      peak were considered as output variables. Fractional factorial experimental
      design has been proved to produce sufficient input data for ANN approximation and
      thus further allowed decreasing the number of experiments necessary for
      optimisation. After the optimal separation conditions were found, fractions with
      peptides were collected and their analysis using off-line matrix assisted laser
      desorption/ionisation time of flight mass spectrometry (MALDI-TOF-MS) was
      performed.

PMID- 16301070
TI  - Identification of Africanized honeybees.
AB  - Gas chromatography and pattern recognition methods were used to develop a
      potential method for differentiating European honeybees from Africanized
      honeybees. The test data consisted of 237 gas chromatograms of hydrocarbon
      extracts obtained from the wax glands, cuticle, and exocrine glands of European
      and Africanized honeybees. Each gas chromatogram contained 65 peaks corresponding
      to a set of standardized retention time windows. A genetic algorithm (GA) for
      pattern recognition was used to identify features in the gas chromatograms
      characteristic of the genotype. The pattern recognition GA searched for features
      in the chromatograms that optimized the separation of the European and
      Africanized honeybees in a plot of the two or three largest principal components
      of the data. Because the largest principal components capture the bulk of the
      variance in the data, the peaks identified by the pattern recognition GA
      primarily contained information about differences between gas chromatograms of
      European and Africanized honeybees. The principal component analysis routine
      embedded in the fitness function of the pattern recognition GA acted as an
      information filter, significantly reducing the size of the search space since it
      restricted the search to feature sets whose principal component plots showed
      clustering on the basis of the bees' genotype. In addition, the algorithm focused
      on those classes and/or samples that were difficult to classify as it trained
      using a form of boosting. Samples that consistently classify correctly are not as
      heavily weighted as samples that are difficult to classify. Over time, the
      algorithm learns its optimal parameters in a manner similar to a neural network.
      The pattern recognition GA integrates aspects of artificial intelligence and
      evolutionary computations to yield a "smart" one-pass procedure for feature
      selection and classification.

PMID- 16301071
TI  - Use of Legendre moments for the fast comparison of two-dimensional polyacrylamide
      gel electrophoresis maps images.
AB  - In this paper, Legendre moments are calculated to extract the global information
      from a set of two-dimensional polyacrylamide gel electrophoresis map images. The
      dataset contains 18 samples belonging to two different cell lines (PACA44 and
      T3M4) of control (untreated) and drug-treated pancreatic ductal carcinoma cells.
      The aim of this work was to obtain the correct classification of the 18 samples,
      using the Legendre moments as discriminant variables. For each image the Legendre
      moments up to a maximum order of 100 were computed. The stepwise linear
      discriminant analysis (LDA) was performed in order to select the moments with the
      highest discriminating power. The results demonstrate that the Legendre moments
      can be successfully applied for fast classification purposes and similarity
      analysis.

PMID- 16301072
TI  - A column capacity study of single, serial, and parallel linked rod monolithic
      high performance liquid chromatography columns.
AB  - The loading capacity of rod monolithic C18 columns was found to be sensitive to
      the injection volume, but essentially insensitive to the mass loading for a
      separation of oligostyrenes. When rod monoliths were coupled in series the
      injection volume loading increased, as too did the resolution of the oligomers,
      but at the expense of separation time. The volume load capacity of these serially
      connected monoliths was, however, not directly proportional to the number of
      columns connected. The volume load capacity was, however, directly proportional
      to the number of columns when the monoliths were connected in parallel and the
      flow stream split between each of the monolithic channels. When the number of
      monoliths in each channel equaled the number of monoliths that were connected in
      a single channel serial system the peak capacity and retention time was
      equivalent for both systems, but the volume load capacity of the parallel system
      was twice that of the serial connection each time the number of channels doubled.
      The results of this study indicate that parallel connection of rod monolithic
      columns may be useful for preparative scale and multidimensional separations
      where it is important that the volume load capacity is high.

PMID- 16301073
TI  - Classification of gasoline data obtained by gas chromatography using a piecewise
      alignment algorithm combined with feature selection and principal component
      analysis.
AB  - A fast and objective chemometric classification method is developed and applied
      to the analysis of gas chromatography (GC) data from five commercial gasoline
      samples. The gasoline samples serve as model mixtures, whereas the focus is on
      the development and demonstration of the classification method. The method is
      based on objective retention time alignment (referred to as piecewise alignment)
      coupled with analysis of variance (ANOVA) feature selection prior to
      classification by principal component analysis (PCA) using optimal parameters.
      The degree-of-class-separation is used as a metric to objectively optimize the
      alignment and feature selection parameters using a suitable training set thereby
      reducing user subjectivity, as well as to indicate the success of the PCA
      clustering and classification. The degree-of-class-separation is calculated using
      Euclidean distances between the PCA scores of a subset of the replicate runs from
      two of the five fuel types, i.e., the training set. The unaligned training set
      that was directly submitted to PCA had a low degree-of-class-separation (0.4),
      and the PCA scores plot for the raw training set combined with the raw test set
      failed to correctly cluster the five sample types. After submitting the training
      set to piecewise alignment, the degree-of-class-separation increased (1.2), but
      when the same alignment parameters were applied to the training set combined with
      the test set, the scores plot clustering still did not yield five distinct
      groups. Applying feature selection to the unaligned training set increased the
      degree-of-class-separation (4.8), but chemical variations were still obscured by
      retention time variation and when the same feature selection conditions were used
      for the training set combined with the test set, only one of the five fuels was
      clustered correctly. However, piecewise alignment coupled with feature selection
      yielded a reasonably optimal degree-of-class-separation for the training set
      (9.2), and when the same alignment and ANOVA parameters were applied to the
      training set combined with the test set, the PCA scores plot correctly classified
      the gasoline fingerprints into five distinct clusters.

PMID- 16301074
TI  - Solving liquid chromatography mass spectrometry coelution problems in the
      analysis of environmental samples by multivariate curve resolution.
AB  - Multivariate curve resolution-alternating least squares (MCR-ALS) is shown to be
      a powerful tool to resolve coelution problems in liquid chromatograpy-mass
      spectrometry (LC-MS) in scan mode. This investigation was performed using two
      types of LC columns, one traditional LC column of 25 cm length with a slow
      gradient and a shorter LC column of 7.5 cm with a rapid gradient which allowed
      much faster analysis and save of reagents and solvents. Mixtures of multiple
      biocide compounds were simultaneously analyzed in standard mixtures and in
      environmental samples (sediment and wastewater samples) with little sample
      pretreatment. Using the more traditional LC 25 cm column, all biocide compounds
      were properly resolved by MCR-ALS and quantitatively analyzed with estimated
      errors always below 20%. When fast chromatography (LC column of 7.5 cm) was used,
      MCR-ALS resolution of the more strongly coeluted compounds was also achieved but
      limitations were found in their simultaneous quantitative determination,
      specially for environmental samples.

PMID- 16301075
TI  - Robust interpretive optimisation in high-performance liquid chromatography
      considering uncertainties in peak position.
AB  - In the context of interpretive chromatographic optimisation, robustness is
      usually calculated by introducing deliberated shifts in the nominal optimal
      conditions and evaluating their effects on the monitored objective function,
      mimicking thus the experimental procedures used in method validation. However,
      such strategy ignores a major source of error: the uncertainties associated to
      the modelling step, that may give rise to deceiving results when conditions that
      were expected to yield baseline separation are reproduced in the chromatograph.
      Two approaches, based on the peak purity concept, are here proposed to evaluate
      the robustness of the objective function under the perspective of measurement
      errors and modelling. The first approach implements these uncertainties as an
      extra band broadening for each chromatographic peak. The second one implements
      them as peak fluctuations in simulated replicated assays, which gives rise to a
      distribution of peak purities, easily computed through Monte-Carlo simulations.
      Both approaches predict satisfactorily a decreased separation capability, with
      respect to the conventional approach, for those situations where the
      uncertainties in peak position make the objective function critical. The first
      approach is less optimistic and formally less rigorous than the second one, but
      its computation is simpler. It can be used to map the critical resolution
      regions, to be comprehensively appraised further by the slower, although more
      rigorous, Monte-Carlo approach.

PMID- 16301076
TI  - Automatic program for peak detection and deconvolution of multi-overlapped
      chromatographic signals part I: peak detection.
AB  - A series of two papers describing a procedure for automated peak deconvolution is
      presented. The goal is to develop a package of routines that can be used by non
      experienced users. Part I (this paper) concerns peak detection, whereas Part II
      is dedicated to the deconvolution itself. In this first part, the most
      interesting features of the peak detection algorithms, which precede the
      deconvolution step, are outlined. High-order derivatives provide valuable
      information to assess the number of underlying compounds under a given peak
      cluster. A smoothing technique was found essential to compute properly the
      derivatives, since the noise is amplified when differences are calculated. The
      Savitsky-Golay smoother was applied in combination with the Durbin-Watson
      criterion to automate the window size selection. This strategy removed the noise
      without loosing valuable information. In some cases, it was found preferable to
      split the chromatogram in different elution regions, and apply the Durbin-Watson
      test and the Savitsky-Golay smoother to each region, separately. The derivatives
      allowed obtaining estimates of both peak parameters and the corresponding ranges
      for each eluting compound to be used in the deconvolution. An algorithm oriented
      to compare peaks from different chromatograms is also presented to perform
      deconvolution, using information from several related chromatograms.

PMID- 16301077
TI  - Automatic program for peak detection and deconvolution of multi-overlapped
      chromatographic signals part II: peak model and deconvolution algorithms.
AB  - Several interlinked algorithms for peak deconvolution by non-linear regression
      are presented. These procedures, together with the peak detection methods
      outlined in Part I, have allowed the implementation of an automatic method able
      to process multi-overlapped signals, requiring little user interaction. A
      criterion based on the evaluation of the multivariate selectivity of the
      chromatographic signal is used to auto-select the most efficient deconvolution
      procedure for each chromatographic situation. In this way, non-optimal local
      solutions are avoided in cases of high overlap, and short computation times are
      obtained in situations of high resolution. A new algorithm, fitting both the
      original signal and the second derivatives is proved to avoid local optima in
      intermediate coelution situations. This allows achieving the global optimum
      without the need of background knowledge by the user. A previously reported peak
      model, a Gaussian with a polynomial standard deviation whose complexity can be
      modulated to enhance the fitting quality, was applied. However, the original
      formulation was modified to account baseline outside the peak region. Also, the
      optimal model complexity was auto-selected via error propagation theory. The
      method is able to process simultaneously several related chromatograms. The
      software was tested with both simulated and experimental chromatograms obtained
      with monolithic silica columns.

PMID- 16301078
TI  - Simultaneous resolution of overlapping peaks in high-performance liquid
      chromatography and micellar electrokinetic chromatography with diode array
      detection using augmented iterative target transformation factor analysis.
AB  - In this paper, augmentation has been applied to data matrices, which originate
      from hyphenated methods that share the same mode of detection, but use different
      separation methods, HPLC-DAD and MEKC-DAD. A novel method, wavelength shift
      eigenstructure tracking (WET), has been proposed for the alignment between the
      wavelength scale of both detectors. WET proves to be suitable for the detection
      as well as correction of wavelength shift between both detectors. After
      correction of the wavelength scale, data obtained on both systems have been
      augmented and submitted to iterative target transformation factor analysis.
      Augmented curve resolution provides significantly better estimates of the
      chromatographic and electrophoretic profiles and spectra than the use of non
      augmented curve resolution on HPLC and MEKC data separately. It is particularly
      useful when the pure fraction of a chromatographic peak is less than 0.10.
      Finally, the relative weight of MEKC versus HPLC in augmentation may be increased
      using intensity and noise normalisation. However, since noise normalisation and
      its accompanying decrease in signal-to-noise ratio leads to a loss of
      information, and, since intensity normalisation may cause a failure of the
      augmented curve resolution algorithm, benefits and drawbacks of normalisation
      should be weighed on a case-by-case basis.

PMID- 16301079
TI  - Prediction of total green tea antioxidant capacity from chromatograms by
      multivariate modeling.
AB  - In this paper, a fast strategy for determining the total antioxidant capacity of
      Chinese green tea extracts is developed. This strategy includes the use of
      experimental techniques, such as fast high-performance liquid chromatography
      (HPLC) on monolithic columns and a spectrophotometric approach to determine the
      total antioxidant capacity of the extracts. To extract the chemically relevant
      information from the obtained data, chemometrical approaches are used. Among them
      there are correlation optimized warping (COW) to align the chromatograms, robust
      principal component analysis (robust PCA) to detect outliers, and partial least
      squares (PLS) and uninformative variable elimination partial least squares (UVE
      PLS) to construct a reliable multivariate regression model to predict the total
      antioxidant capacity from the fast chromatograms.

PMID- 16301080
TI  - Selection of orthogonal reversed-phase HPLC systems by univariate and auto
      associative multivariate regression trees.
AB  - In order to select chromatographic starting conditions to be optimized during
      further method development of the separation of a given mixture, so-called
      generic orthogonal chromatographic systems could be explored in parallel. In this
      paper the use of univariate and multivariate regression trees (MRT) was studied
      to define the most orthogonal subset from a given set of chromatographic systems.
      Two data sets were considered, which contain the retention data of 68
      structurally diversive drugs on sets of 32 and 38 chromatographic systems,
      respectively. For both the univariate and multivariate approaches no other data
      but the measured retention factors are needed to build the decision trees. Since
      multivariate regression trees are used in an unsupervised way, they are called
      auto-associative multivariate regression trees (AAMRT). For all decision trees
      used, a variable importance list of the predictor variables can be derived. It
      was concluded that based on these ranked lists, both for univariate and
      multivariate regression trees, a selection of the most orthogonal systems from a
      given set of systems can be obtained in a user-friendly and fast way.

PMID- 16301081
TI  - Diabetes mellitus in children.

PMID- 16301082
TI  - The classification of diabetes mellitus: a conceptual framework.
AB  - Diabetes is the extreme manifestation of a spectrum conditions in which the
      balance of insulin secretion and insulin action (or insulin resistance) has been
      altered. Loss of euglycemia is caused by relative insulin deficiency in the
      presence of insulin resistance, or by absolute insulin deficiency. There are
      related conditions in which an alteration of insulin resistance or beta-cell
      dysfunction exists, but because of compensation glucose homeostasis has not been
      lost. The elucidation of the causes of insulin resistance and -cell failure and
      the attention to the different degrees of insulin deficiency and insulin
      resistance allow for better diagnosis, treatment, and prevention of diabetes and
      its related conditions.

PMID- 16301083
TI  - Type 1 diabetes mellitus: etiology, presentation, and management.
AB  - This article reviews our current understanding of the etiology, presentation, and
      management of type 1 diabetes. The discussion includes a review of the natural
      history of diabetes, the complex relationship between genetic and environmental
      risk for type 1 diabetes, and current methods for prediction of type 1 diabetes.
      The article also reviews the current management of children who have new-onset
      type 1 diabetes, age-appropriate management goals, and diabetes complications.
      Finally, the article discusses the future of diabetes screening programs and the
      progress toward the ultimate goal of curing type 1 diabetes.

PMID- 16301084
TI  - Type 2 diabetes mellitus in youth: the complete picture to date.
AB  - Type 2 diabetes mellitus is a heterogeneous condition in which the clinical
      manifestation of hyperglycemia is a reflection of the impaired balance between
      insulin sensitivity and insulin secretion. Clinical experience and research in
      youth type 2 diabetes mellitus are in an early stage because of the relative
      novelty of the condition in pediatrics. This article discusses the amassed
      information in type 2 diabetes mellitus of youth to date with respect to the
      epidemiology, pathophysiology, risk factors, clinical presentation, screening,
      and management strategies.

PMID- 16301085
TI  - Pediatric diabetic ketoacidosis and hyperglycemic hyperosmolar state.
AB  - Diabetic ketoacidosis is an important complication of diabetes in children and is
      the most frequent diabetes-related cause of death in childhood. The
      pathophysiology of this condition can be viewed as an exaggeration of the normal
      physiologic mechanisms responsible for maintaining an adequate fuel supply to the
      brain and other tissues during periods of fasting and physiologic stress. The
      optimal therapy has been a subject of controversy, particularly because the most
      frequent serious complication of diabetic ketoacidosis-cerebral edema-and the
      relationship of this complication to treatment are incompletely understood. In
      this article, the author reviews the pathophysiology of diabetic ketoacidosis and
      its complications and presents an evidence-based approach to the management of
      this condition.

PMID- 16301086
TI  - Monogenic and other unusual causes of diabetes mellitus.
AB  - This article covers some unusual or rare causes of diabetes mellitus chosen not
      necessarily on the basis of frequency or rarity, but rather on the basis of how
      well the disease and its implications in diabetes management is understood. A
      specific diagnosis is of help in these rare syndromes but not absolutely
      necessary for optimal management. The basic principles of diabetes management are
      well-defined, regardless of etiology. What is important is to understand the
      relative contribution of insulin resistance versus insulin deficiency, regardless
      of etiology, as the most important guide to management.

PMID- 16301087
TI  - Insulin analogues in children and teens with type 1 diabetes: advantages and
      caveats.
AB  - This article reviews the advantages to and caveats of the use of newer insulin
      formulations (insulin analogues) and regimens in children and teens who have type
      1 diabetes, their affect on glycemic control, frequency of hypoglycemic events,
      daily insulin requirements, and adverse affects such as excessive weight gain,
      which provides a further major challenge in adolescents. We also address briefly
      the use of adjunctive agents in the treatment of type 1 diabetes in children and
      teens.

PMID- 16301088
TI  - Insulin pump treatment of childhood type 1 diabetes.
AB  - Current goals for the treatment of children and adolescents with type 1 diabetes
      mellitus include achieving near-normal blood sugar levels, minimizing the risk of
      hypoglycemia, optimizing quality of life, and preventing or delaying long-term
      microvascular complications. Continuous subcutaneous insulin infusion (CSII)
      provides a treatment option that can assist in the attainment of all of these
      goals in all ages of children. Usage of CSII has been demonstrated to reduce
      glycosylated hemoglobin levels and frequency of severe hypoglycemia, without
      sacrifices in safety, quality of life, or weight gain, particularly in
      conjunction with the use of new insulin analogs and improvements in pump
      technology. Clinical studies of safety and efficacy of CSII in children are
      reviewed.

PMID- 16301089
TI  - Oral agents in managing diabetes mellitus in children and adolescents.
AB  - Type 2 diabetes mellitus is a chronic disease with potentially devastating long
      term complications. Despite the tremendous body of research and experience in the
      adult population, relatively little is established regarding this condition and
      its optimal management in children and adolescents. The pediatric community
      awaits results of ongoing trials as well as further study of optimal intervention
      in children, as they continue to extrapolate management practices from their
      adult counterparts.

PMID- 16301090
TI  - Hypoglycemia: a complication of diabetes therapy in children.
AB  - The experience of hypoglycemia is probably the most feared and hated consequence
      of life with type 1 diabetes among pediatric patients and their parents. Although
      transient detrimental effects are clearly disturbing and may have severe results,
      there is surprisingly little evidence of long-term CNS damage, even after
      multiple hypoglycemic episodes, except in rare instances. Despite the latter
      evidence, we advocate that every treatment regimen be designed to prevent
      hypoglycemia without inducing unacceptable hyperglycemia and increasing the risk
      of micro- and macrovascular complications.

PMID- 16301091
TI  - Complications of diabetes mellitus in childhood.
AB  - Complications of diabetes include retinopathy, nephropathy, neuropathy,
      macrovascular disease, and associated autoimmune diseases. Clinical
      manifestations of complications uncommonly present in childhood and adolescence.
      Screening during the early years can identify subclinical disease and it offers
      an opportunity for early intervention. The Diabetes and Complications Control
      Trial has provided evidence for the long-term benefits of good glycemic control
      in preventing and delaying the onset of microvascular complications.
      Complications begin to manifest during adolescence, during which time all efforts
      should be made to educate and support young persons in achieving optimal diabetes
      control.

PMID- 16301092
TI  - The psychologic context of pediatric diabetes.
AB  - During the past few decades, there has been an explosion of behavioral science
      research on family management of pediatric diabetes. This article distills the
      major conclusions from that literature, emphasizing how primary care providers
      can apply these findings in clinical practice.

PMID- 16301093
TI  - A look to the future: prediction, prevention, and cure including islet
      transplantation and stem cell therapy.
AB  - Type 1 diabetes mellitus (T1DM) is characterized by the almost complete absence
      of insulin secretion, which is secondary to an autoimmune destruction or
      dysfunction of the insulin-producing cells of the pancreatic islets of
      Langerhans. Because T1DM is an autoimmune disease with a long preclinical course,
      the predictive testing of individuals before the clinical onset of the disease
      has provided a real opportunity for the identification of risk markers and the
      design of therapeutic intervention. With such a high degree of predictability
      using a combination of immunologic markers, strategies to prevent T1DM may become
      possible. A number of novel therapeutic strategies are under investigation in
      newly diagnosed T1DM patients and might ultimately be applied to prevent T1DM.

PMID- 16301095
TI  - Sleep and cardiovascular disease.
AB  - Sleep is an important modulator of cardiovascular function, both in physiological
      conditions and in disease states. In individuals without a primary sleep
      disorder, sleep may exert significant effects on the autonomic nervous system,
      systemic hemodynamics, cardiac function, endothelial function, and coagulation.
      Some of these influences can be directly linked to specific modulatory effects of
      sleep stages per se; others result from the natural circadian rhythm of various
      physiological processes. There is a temporal association between physiological
      sleep and occurrence of vascular events, cardiac arrhythmias, and sudden death.
      Epidemiological and pathophysiological studies also indicate that there may be a
      causal link between primary sleep abnormalities (sleep curtailment, shift work,
      and sleep-disordered breathing) and cardiovascular and metabolic disease, such as
      hypertension, atherosclerosis, stroke, heart failure, cardiac arrhythmias, sudden
      death, obesity, and the metabolic syndrome. Finally, sleep disturbances may occur
      as a result of several medical conditions (including obesity, chronic heart
      failure, and menopause) and may therefore contribute to cardiovascular morbidity
      associated with these conditions. Further understanding of specific
      pathophysiological pathways linking sleep disorders to cardiovascular disease is
      important for developing therapeutic strategies and may have important
      implications for cardiovascular chronotherapeutics.

PMID- 16301096
TI  - Chronic low-level mercury exposure, BDNF polymorphism, and associations with
      cognitive and motor function.
AB  - Potential cognitive and motor effects from exposure to elemental mercury (Hg(0))
      were examined in the presence and absence of a polymorphism (Val66Met) in brain
      derived neurotrophic factor (BDNF). A group of 194 male dentists (DDs) and 233
      female dental assistants (DAs) were occupationally exposed to mercury and had no
      history of kidney or nervous system disorders. Acute exposure was measured using
      spot urinary Hg (HgU) concentrations (average 3.32 and 1.98 microg/l,
      respectively) and indices of chronic occupational exposure (26.3 and 14.9 years,
      respectively, weighted for historical exposures). The BDNF status was 68% and 66%
      wild type, 26% and 30% single substitution, and 5% and 4% full mutation for DDs
      and DAs, respectively. DDs and DAs were evaluated separately. Regression analyses
      controlled for age, premorbid intelligence, alcohol consumption, and education.
      Statistically significant adverse associations with HgU (p<.05) were found for
      nine measures among DDs (Digit Span (Forward), Digit and Spatial Span(Backward),
      Visual Reproduction, Finger Tapping(Dominant, Alternate, and Alternate
      Partialed), Hand Steadiness, and Tracking), and eight measures among DAs (Digit
      Span(Forward), Visual Reproduction, Pattern Discrimination(Rate), Symbol
      Digit(Rate), Trailmaking B, Finger Tapping(Dominant and Alternate Partialed), and
      Hand Steadiness). The BDNF status was associated with four measures in DDs and
      three measures in DAs. Joint effects were found for Finger Tapping(Alternate and
      Alternate Partialed) in DDs and Hand Steadiness and Trailmaking B in DAs. Joint
      effects were additive in all cases. Performance on verbal intelligence and
      reaction time were not associated with either HgU or BDNF status. A test of
      threshold effect for the association of Hand Steadiness with HgU demonstrated no
      lower boundary in both DDs and DAs. No associations were observed with estimates
      of chronic mercury exposure. Our findings are applicable to exposure levels of
      the general population and identify a potentially vulnerable group with a BDNF
      polymorphism.

PMID- 16301097
TI  - Genetics of vocal quality characteristics in monozygotic twins: a multiparameter
      approach.
AB  - The main purpose of this study was to determine the vocal quality characteristics
      among the 45 monozygotic cotwins (MT). As the performance of the voice is related
      to several genetically determined anatomical and physiological factors, the
      authors hypothesized that the vocal characteristics and the overall vocal quality
      by means of the Dysphonia Severity Index (DSI) will be identical in MT. An
      additional objective of this study was to determine whether sex and age influence
      vocal similarities in MT and to compare the voice characteristics of MT with the
      normative data of unrelated peers. As more environmental factors influence the
      aging of the voice, age-related differences were expected. No sex-related
      differences were expected. Subjective and objective assessment techniques
      determined the vocal quality. No significant differences were obtained, and most
      comparisons resulted in significant correlation coefficients. For the acoustic
      parameters jitter and shimmer only, no significant correlation coefficients could
      be obtained. It is clear that the perceptual voice characteristics, the laryngeal
      aerodynamic measurements of maximum phonation time (MPT), the vocal performances,
      and the overall vocal quality by means of the DSI are similar in MT. These vocal
      characteristics are not influenced either by the subjects' age or sex and are
      situated within the normative range of unrelated peers. To what extent other
      aspects (environment, anxiety, tension, etc) might play a role in the acoustical
      dimensions regarding frequency and amplitude perturbation, which were in the
      normal range, is a subject of further research.

PMID- 16301098
TI  - Perturbation and nonlinear dynamic analyses of voices from patients with
      unilateral laryngeal paralysis.
AB  - This study used perturbation methods (eg, jitter and shimmer) and nonlinear
      dynamic methods (eg, phase space reconstruction and correlation dimension) to
      analyze sustained voices generated by normal subjects and patients with
      unilateral laryngeal paralysis. We found that normal and pathological voices had
      low-dimensional dynamic characteristics. For nearly periodic voices, jitter and
      shimmer values of pathological voices from patients with unilateral laryngeal
      paralysis were significantly different from normal voices. For nearly periodic
      and aperiodic voices, the correlation dimensions of pathological voices were
      statistically higher than normal voices. Receiver operating characteristic
      analysis was used to evaluate the diagnostic performances of jitter, shimmer, and
      correlation dimension. High sensitivity and specificity of these three acoustic
      analyses in distinguishing unilateral laryngeal paralysis patients from normal
      subjects were found. We concluded that combining traditional perturbation
      analysis and nonlinear dynamic analysis might provide efficient descriptions of
      pathological voices and represent a valuable tool for clinical diagnosis of
      laryngeal paralysis.

PMID- 16301099
TI  - Histopathological changes of vocal folds induced by chronic pollutant exposure:
      an experimental study.
AB  - Calcium carbonate (CaCO(3)) particles, the main component of chalk, are an
      important pollutant in the Brazilian school environment. However, there are few
      reports of the effect of this pollutant in the vocal folds and its influence in
      voice disorder in the literature. METHODS: Thirty rats (Wistar), randomly divided
      into two groups, the control group and the experimental group, were submitted to
      air or to CaCO(3) inhalation, respectively, during 15, 30, and 90 days. Then, the
      larynx region was dissected and embedded in paraffin, and 5-mum sections were
      obtained for microscopic analysis. RESULTS: No histopathological alteration was
      found on the vocal folds in the control group. In the experimental group, a
      moderate chronic inflammatory infiltrate, characterized by macrophage cells, was
      found in the vocal folds after 30 and 90 days of the CaCO(3) inhalation.
      CONCLUSIONS: This study suggests that the inhalation of pollutant particles, such
      as CaCO(3), induces inflammatory alterations in the larynx; this can affect the
      vibration of the vocal folds, which influence vocal function.

PMID- 16301100
TI  - The relationship between vocal pitch-matching skills and pitch discrimination
      skills in untrained accurate and inaccurate singers.
AB  - Few studies have compared the relationship between pitch discrimination accuracy
      and the accuracy of fundamental frequency (F(o)) control. This study investigated
      the relationship between vocal pitch-matching skills, which is one method of
      testing F(o) control, and pitch discrimination skills in untrained accurate and
      inaccurate singers, and the effect of timbre on their pitch discrimination
      accuracy. Data showed that accurate singers had more precise discrimination and
      pitch-matching abilities compared with their inaccurate counterparts. Pitch
      discrimination was differentially affected by the timbre (eg, spectral
      differences) of comparison tones. In addition, results showed a significant
      relationship between pitch discrimination abilities and pitch-matching accuracy.
      The results suggest that accurate F(o) control is at least partially dependent on
      pitch discrimination abilities, which are important for accurate singing.

PMID- 16301101
TI  - The relative contributions of speaking fundamental frequency and formant
      frequencies to gender identification based on isolated vowels.
AB  - The purpose of this study was to determine the accuracy with which listeners
      could identify the gender of a speaker from a synthesized isolated vowel based on
      the natural production of that speaker when (1) the fundamental frequency was
      consistent with the speaker's gender, (2) the fundamental frequency was
      inconsistent with the the speaker's gender, and (3) the speaker was
      transgendered. Ten male-to-female transgendered persons, 10 men and 10 women,
      served as subjects. Each speaker produced the vowels /i/, /u/, and //. These
      vowels were analyzed for fundamental frequency and the first three formant
      frequencies and bandwidths. Formant frequency and bandwidth information was used
      to synthesize two vowel tokens for each speaker, one at a fundamental frequency
      of 120 Hz and one at 240 Hz. Listeners were asked to listen to these tokens and
      determine whether the original speaker was male or female. Listeners were not
      aware of the use of transgendered speakers. Results showed that, in all cases,
      gender identifications were based on fundamental frequency, even when fundamental
      frequency and formant frequency information was contradictory.

PMID- 16301102
TI  - Reliability in perceptual analysis of voice quality.
AB  - This study focuses on speaking voice quality in male teachers (n = 35) and male
      actors (n = 36), who represent untrained and trained voice users, because we
      wanted to investigate normal and supranormal voices. In this study, both
      substantial and methodologic aspects were considered. It includes a method for
      perceptual voice evaluation, and a basic issue was rater reliability. A listening
      group of 10 listeners, 7 experienced speech-language therapists, and 3 speech
      language therapist students evaluated the voices by 15 vocal characteristics
      using VA scales. Two sets of voice signals were investigated: text reading (2
      loudness levels) and sustained vowel (3 levels). The results indicated a high
      interrater reliability for most perceptual characteristics. Connected speech was
      evaluated more reliably, especially at the normal level, but both types of voice
      signals were evaluated reliably, although the reliability for connected speech
      was somewhat higher than for vowels. Experienced listeners tended to be more
      consistent in their ratings than did the student raters. Some vocal
      characteristics achieved acceptable reliability even with a smaller panel of
      listeners. The perceptual characteristics grouped in 4 factors reflected
      perceptual dimensions.

PMID- 16301103
TI  - The effect of speaking task on perceptual judgment of the severity of dysphonic
      voice.
AB  - This study investigated the effect of speaking task on auditory-perceptual
      judgment of the severity of dysphonia. Three speech-language pathologists
      experienced in evaluating of disordered voices rated 29 recorded speakers, each
      of whom produced speech elicited via the same three tasks: sustained vowel /a/,
      oral reading of a standard passage, and connected speech describing a standard
      picture. Stimuli were played in sound field, and raters used direct magnitude
      estimation with a visual analog scale. A repeated measures analysis of variance
      (ANOVA) revealed a statistically significant (P < .05) effect of speaking task,
      with post hoc analyses that indicate a statistically significant difference
      between ratings for the sustained vowel versus connected speech elicited via
      picture description (P < .05). No statistically significant difference in ratings
      was found between oral reading and picture description or between oral reading
      and the sustained vowel. The ANOVA also revealed a statistically significant
      difference among raters (P < 0.001), but no statistically significant task by
      rater interaction. Possible reasons for an effect of speaking task are discussed.
      Also, the implications of one task for determination of dysphonic severity are
      discussed, as is the possibility of a task effect when determining other
      clinically useful vocal parameters.

PMID- 16301104
TI  - Revisiting the pitch controversy: changes in speaking fundamental frequency (SFF)
      after management of functional dysphonia.
AB  - Speaking fundamental frequency (SFF) and its perceptual correlate "habitual
      pitch" have been considered important and contentious parameters in voice
      assessment and treatment. In clinical circles, disagreement exists regarding the
      role of habitual pitch in the development, maintenance, and treatment of
      disordered voices. Despite these divergent opinions, few studies have objectively
      evaluated SFF changes associated with voice improvement after therapy. To
      determine whether consistent directional and magnitude changes in SFF occur after
      management, pretreatment and posttreatment audio recordings of 40 women with
      functional dysphonia were analyzed. All subjects were treated with manual
      circumlaryngeal therapy, a treatment approach that does not directly target pitch
      as a perceptual entity to be manipulated. Results indicated that, as a group, no
      significant change in mean SFF was observed after successful management. Although
      no consistent directional pattern was identified, 80% of the subjects experienced
      pitch changes greater than one semitone; this suggests that voice improvement is
      often accompanied by a shift in SFF. Clinical implications of the data are
      discussed.

PMID- 16301105
TI  - Fundamental frequency in speakers of Portuguese for different voice samples.
AB  - The purpose of this research was to obtain information on the mean fundamental
      frequency (Fo) levels of Portuguese speakers and to investigate (1) whether
      differences exist between two groups with different voice qualities (normal and
      dysphonia), genders, ages, and speech tasks; and (2) which variables contribute
      to the variance. To this end, 109 subjects (52 dysphonics and 57 controls)
      participated in the study. Speech material included three sustained vowels ([u],
      [i], and [a]), a standard written passage, and a conversation produced at a
      comfortable conversational pitch and loudness level. Electroglottographic (EGG)
      data were obtained. Although the results show that, overall, the dysphonics had
      lower Fo than did controls for all speaking conditions, and that there were
      differences according to age, these contrasts were not statistically significant.
      Gender and speech task effects were statistically significant. Additionally, the
      mean Fo variance is explained by a high prediction model (between 59% and 73%).

PMID- 16301106
TI  - Resonant voice: spectral and nasendoscopic analysis.
AB  - Although resonant voice therapy is a widely used therapeutic approach, little is
      known about what characterizes resonant voice and how it is physiologically
      produced. The purpose of this study was to test the hypothesis that resonant
      voice is produced by narrowing the laryngeal vestibule and is characterized by
      first formant tuning and more ample harmonics. Videonasendoscopic recordings of
      the laryngeal vestibule were made during nonresonant and resonant productions of
      /i/ in six subjects. Spectrums of the two voice types were also obtained.
      Spectral analysis showed that first formant tuning was exhibited during resonant
      voice productions and that the degree of harmonic enhancement in the range of 2.0
      to 3.5 kHz was related to voice quality: nonresonant voice had the least amount
      of energy in this range, whereas a resonant-relaxed voice had more energy, and a
      resonant-bright voice had the greatest amount of energy. Visual-perceptual
      judgments of the videoendoscopic data indicated that laryngeal vestibule
      constriction was not consistently associated with resonant voice production.

PMID- 16301107
TI  - Neck and shoulder muscle activity and thorax movement in singing and speaking
      tasks with variation in vocal loudness and pitch.
AB  - The aim of this study was to examine respiratory phasing and loading levels of
      sternocleidomastoideus (STM), scalenus (SC), and upper trapezius (TR) muscles in
      vocalization tasks with variation in vocal loudness and pitch. Eight advanced
      singing students, aged 22 to 28 years, participated. Surface electromyographic
      (EMG) activity was recorded from STM, SC, and TR. Thorax movement was detected by
      two strain gauge sensors placed around the upper (upper TX) and lower (lower TX)
      thorax. A glissando and simplified singing and speaking tasks were performed.
      Sustained vowels /a:-i-ae-o:/ were sung in a glissando from lowest to highest
      pitch (mixed voice/falsetto) back to lowest pitch and in short singing sequences
      at comfortable, low, and high pitches. The same vowels were spoken softly and
      loudly for about the same length. The subjects inhaled between the vowels. It was
      concluded that the inspiratory phased STM and SC muscles produced a counterforce
      to compression of upper TX at high pitches in glissando. STM and SC were
      activated to higher levels during phonation than in inhalation. As breathing
      demands were reduced, STM and SC activity was lowered and the respiratory phasing
      of peak amplitude changed to inhalation. TR contributed to exhalation in
      demanding singing with long breathing cycles, but it was less active in singing
      tasks with short breathing cycles and was essentially inactive in simplified
      speaking tasks.

PMID- 16301108
TI  - Effects of topical anesthetic and flexible fiberoptic laryngoscopy on
      professional sopranos.
AB  - This study examined the acoustic and perceptual effects of topical anesthetic and
      flexible fiberoptic laryngoscopy (FFL) against a control condition on the singing
      voices of ten professional sopranos. Recordings of a section of an aria, various
      scales, and a messa di voce exercise were obtained in the three experimental
      conditions. Acoustic analyses of the same aria section recorded during the three
      conditions were similar with respect to the distribution of energy across the
      spectrum (LTAS) and vibrato rate and extent. The ability of the participants to
      achieve their highest and lowest notes or to complete the messa di voce was also
      not affected by the anesthetic or FFL. Perceptual ratings of a variety of
      parameters by experienced singing teachers also revealed little difference across
      conditions with only "appropriate velopharyngeal closure" found to differ in one
      comparison. These results indicate that highly experienced operatic sopranos are
      either not affected by or appear to have the ability to compensate for the
      presence of anesthetic and the FFL. The most likely explanation is that this
      group of singers relied on a solid vocal technique. Results will need to be
      replicated on less accomplished singers before concluding that this medical
      procedure does not affect the operatic singing voice.

PMID- 16301109
TI  - Vocal cord medialization by transcutaneous injection of calcium hydroxylapatite.
AB  - Transcutaneous vocal cord augmentation has increasingly become the method of
      choice when treating causes of vocal cord insufficiency. Many substances have
      accompanied this technique, but they all have problems. One newer substance is
      calcium hydroxylapatite (CaHA). CaHA may produce fewer problems and offer a
      longer-lasting treatment. Twenty-one patients were treated in the Pacific Voice
      Clinic with trancutaneous injection of CaHA for vocal cord paralysis (n = 19) and
      vocal scarring (n = 2). Maximum phonation time (MPT) was the measure of vocal
      performance. An improvement was seen in 20 patients with the MPT, who improved
      from 4.6 seconds before treatment to 10.8 seconds at posttreatment of 3 months (n
      = 15). This improvement was maintained at 6 months (MPT = 12 seconds, n = 12).
      Follow-up was incomplete because of the terminal nature of some diagnoses and the
      large geographical area covered by the clinic. Three subjects had submucosal
      injection of CaHA (two resolving spontaneously). Two other patients had extrusion
      of the material. With short-term and medial-term follow-up on a small group of
      patients, encouraging results were seen with transcutaneous injection of CaHA for
      vocal cord augmentation.

PMID- 16301110
TI  - Repetitive phonatory tasks for identifying vocal fold paresis.
AB  - Vocal fold paresis may be present in patients with voice complaints.
      Identification of paresis is important so that appropriate neurolaryngologic
      evaluation can be ordered and the appropriate treatment can be offered.
      Repetitive phonatory tasks (RPTs) fatigue patients vocally and may elicit signs
      of subtle paresis. In this study, four laryngologists independently reviewed the
      RPT portions of routine fiberoptic voice examinations of 100 patients in a
      blinded fashion. All patients had presented with voice complaints, were suspected
      of having a movement disorder of the larynx, and had been referred for laryngeal
      electromyography (LEMG). Predictions were compared with LEMG results and with
      predictions made at the time of each initial evaluation. Although RPTs are useful
      to laryngologists, predictions based on the entire examination are more accurate.
      LEMG can confirm clinical suspicions or identify paresis missed on fiberoptic
      laryngeal examination.

PMID- 16301111
TI  - Arytenoid cartilage dislocation: a 20-year experience.
AB  - SUMMARY: Arytenoid cartilage dislocation is an infrequently diagnosed cause of
      vocal fold immobility. Seventy-four cases have been reported in the literature to
      date. Intubation is the most common origin, followed by external laryngeal
      trauma. Decreased volume and breathiness are the most common presenting symptoms.
      We report on 63 patients with arytenoid cartilage dislocation treated by the
      senior author (RTS) since 1983. Significantly more posterior than anterior
      dislocations were represented. Although reestablishing joint mobility is
      difficult, endoscopic reduction should be considered to align the heights of the
      vocal processes. This process may result in significant voice improvement even
      long after the dislocation. Strobovideolaryngoscopy, laryngeal electromyography,
      and laryngeal computed tomography (CT) imaging are helpful in the evaluation of
      patients with vocal fold immobility to help distinguish arytenoid cartilage
      dislocation from vocal fold paralysis. Familiarity with signs and symptoms of
      arytenoid cartilage dislocation and current treatment techniques improves the
      chances for optimal therapeutic results.

PMID- 16301112
TI  - Inhibition of invasiveness of human lung cancer cell line H1299 by over
      expression of cofilin.
AB  - The Rho-LIM-kinase (LIMK) signaling pathway, believed to be involved in the
      regulation of tumor invasion, specifically regulates the activity of cofilin.
      However, it is unclear whether cofilin plays a pivotal role in tumor
      invasiveness. In this paper we show using a tet-on gene expression system that
      over-expression of cofilin inhibits the invasiveness of human lung cancer H1299
      cells. Over-expressed cofilin disrupts the actin cytoskeleton at the leading edge
      of the cell and up-regulates p27(kip1), which is known to be involved in
      regulating cell motility. Removal of cofilin over-expression normalizes the
      p27(kip1) level and concomitantly restores the invasiveness of the cultured
      cells. These findings suggest that excessive cofilin production might prevent
      cancer cell invasion.

PMID- 16301113
TI  - Lycopene as a chemopreventive agent in the treatment of high-grade prostate
      intraepithelial neoplasia.
AB  - OBJECTIVE: Because of its long latency, slow growing nature, and high prevalence,
      prostate cancer is the best model for chemoprevention. High-grade prostate
      intraepithelial neoplasia (HGPIN) is a precursor of prostate cancer.
      Chemoprevention with lycopene has shown definite results in prostate cancer. We
      undertook a study to use lycopene as a chemopreventive agent in the treatment of
      HGPIN for preventing prostate cancer from developing in this vulnerable group of
      patients. MATERIALS AND METHODS: A total of 40 patients with HGPIN were
      randomized into 2 groups: one received 4 mg lycopene twice a day for one year,
      and the other was periodically followed up. Total follow-up was one year.
      RESULTS: Our results show that lycopene can delay or prevent HGPIN from
      developing into occult prostate cancer, and there exists an inverse relationship
      between lycopene and prostate-specific antigen. Being a vegetable carotenoid,
      lycopene is a safe drug to be used for a longer period without any adverse
      reaction. CONCLUSION: Lycopene is an effective chemopreventive agent in the
      treatment of HGPIN, with no toxicity and good patient tolerance.

PMID- 16301115
TI  - Comparisons of prostate cancer mortality rates with dietary practices in the
      United States.
AB  - From 1930 to 1992, prostate cancer mortality rates in the United States doubled
      and then declined somewhat until 2000. The objective of this study is to
      determine whether variations in prostate cancer mortality rates correlate with
      dietary changes that occurred over that period. Simple linear regression models
      were applied to age-adjusted prostate cancer mortality rates and per-capita
      consumption rates for 18 foods from 1930 to 2000. Correlation coefficients were
      calculated while comparing food consumption rates to prostate cancer mortality
      rates for the same year. Correlation coefficients were then recalculated when the
      prostate cancer mortality rates were compared with food consumption rates that
      occurred: 1 yr; 2 yr; 3 yr; and continuing in progression for 21 yr before the
      occurrence of the prostate cancer mortality. The largest positive correlation
      coefficients were associated with the consumption of: total meat (red meat,
      poultry and fish) (R = 0.83, T between 0 and 1); added fats and oils (R = 0.83, T
      = 21); ice cream (R = 0.83, T = 20); margarine (R = 0.81, T = 4); salad/cooking
      oil (R = 0.82, T between 3 and 4) and; vegetable shortening (R = 0.81, T between
      1 and 2) where R is the correlation coefficient and T is the time in years
      between consumption and mortality. In conclusion, this study found strong
      positive correlations between prostate cancer mortality and the consumption of:
      total meat; added fats and oils, ice cream, salad/cooking oils, margarine, and
      vegetable shortening. The connection between total meat consumption and prostate
      cancer risk is consistent with previous studies in the literature. The link
      between salad/cooking oil consumption and prostate cancer risk may be consistent
      with past studies which suggest that mu-linolenic acid (a component of
      salad/cooking oils) is a suspected risk factor for prostate cancer.

PMID- 16301114
TI  - A phase II clinical trial of oral bropirimine in combination with intravesical
      bacillus Calmette-Guerin for carcinoma in situ of the bladder: a Southwest
      Oncology Group Study.
AB  - OBJECTIVES: To estimate the probability of response when intravesical bacille
      Calmette-Guerin (BCG) is given in combination with oral bropirimine for bladder
      carcinoma in situ, and to evaluate toxicity when the 2 agents are combined.
      METHODS: A total of 51 patients with histologic evidence of carcinoma in situ and
      no prior treatment with BCG or bropirimine were enrolled in a cooperative group
      multicenter phase II trial. Initial treatment included Tice BCG 50 mg weekly for
      6 weeks and oral bropirimine 3.0 g/day for 3 consecutive days each week for 12
      weeks. Response was assessed after 12 weeks by cystoscopy, biopsy, and barbotage
      cytology. Most patients received a second course followed by an identical
      assessment. Toxicity was recorded according to the Southwest Oncology Group
      toxicity criteria. RESULTS: A total of 51 patients were enrolled and treated.
      There were 42 patients who were eligible and valuable for response and toxicity.
      There were 28 complete responders (67%, 50% to 80% 95% confidence interval). The
      5-year progression-free survival estimate is 53%, and the 5-year survival
      estimate is 80%. There were no deaths, 2 patients had grade 4 toxicity, 14 grade
      3 toxicity, 17 grade 2 toxicity, 6 grade 1 toxicity, and only 3 had no toxicity
      reported as their worst toxicity grade. CONCLUSIONS: The combination failed to
      show an estimated response higher than 80%. It is not recommended that further
      evaluation of this combination be conducted.

PMID- 16301116
TI  - Immunohistochemical demonstration of gonadotropin-releasing hormone receptors in
      prostate carcinoma.
AB  - The antiandrogen and gonadotropin-releasing hormone (Gn-RH) analogue treatment of
      prostate carcinoma is based on decreased proliferative and increased apoptotic
      activity of tumor cells, induced by androgen ablation. Gn-RH analogues decrease
      the serum level of androgens by breaking the pituitary-gonadal axis, but
      increasing evidence points to the direct effect of Gn-RH analogues on tumor
      cells. Immunohistochemical demonstration of Gn-RH receptors recently became
      possible. Cryostat and paraffin sections of prostate biopsy samples of 10
      untreated patients with prostate carcinoma (T2-T3, Gleason score 5-8) were
      investigated for Gn-RH receptors (Gn-RHR) and androgen receptors, respectively,
      using the immunoperoxidase method. Membrane bound, focal Gn-RHR positivity was
      found in 5 samples. Nuclear androgen receptor positivity appeared in 7 samples.
      No correlation between Gn-RHR and androgen receptor positivity was found, neither
      receptor status and tumor-nodes-metastasis stage nor Gleason score could be
      related to each other. Correlation between Gn-RHR positivity and response to
      luteinizing hormone-releasing hormone analogue treatment will be investigated
      further.

PMID- 16301117
TI  - Aberrant expression of E-cadherin and beta-catenin in human prostate cancer.
AB  - Cadherin-catenin complexes play a key role in embryonic development, and are
      associated with carcinogenesis and metastasis. We studied the expression of the
      major members of the family, including E-cadherin and beta-catenin in prostate
      cancer (PC), and correlated with Gleason grade and pathologic stage.
      Immunohistochemistry was performed on serial sections of paraffinized radical
      prostatectomy specimens to evaluate E-cadherin (n = 16) and beta-catenin (n = 17)
      expression using heat induced epitope retrieval. Benign appearing prostate
      epithelium was used as an internal control in each specimen. Two pathologists
      independently reviewed and scored the intensity and extent of immunostaining
      using a semiquantitative scale. The Mantel-Haenszel method, stratified by
      reviewer, was used to test for an association among Gleason score, pathologic
      stage, and the expression of E-cadherin or beta-catenin in PC. Gleason grade > or
      =7 cancers showed significantly lower expression of E-cadherin and beta-catenin
      compared to Gleason grade < 7 PC, P = 0.015 and 0.025, respectively. In addition,
      beta-catenin was down regulated in 4 of 5 (80%) specimens with identifiable high
      grade prostatic intraepithelial neoplasia and had demonstrable nuclear staining
      in higher grade PC (P = 0.0001). However, E-cadherin and beta-catenin membranous
      or nuclear expressions were not significantly associated with final pathologic
      stage of the specimens (P values >0.05). Overall, the expression of E-cadherin
      and beta-catenin is significantly down regulated in PC compared to surrounding
      benign appearing prostate, which correlates with increasing Gleason grade.
      Furthermore, nuclear localization of beta-catenin in high grade PC may be a
      useful biomarker for aggressive PC.

PMID- 16301118
TI  - Tissue transglutaminase interacts with protein kinase A anchor protein 13 in
      prostate cancer.
AB  - We have previously described that tissue transglutaminase (tTG) is a high level
      phenotypic biomarker in prostate cancer, which is down regulated in prostate
      cancer and surrounding premalignant field compared to benign prostate glands. To
      understand the function of tTG in prostate cancer, we sought to identify proteins
      that interact with the transglutaminase moiety of tTG using a human prostate
      cancer complementary deoxyribonucleic acid library in a Yeast 2-Hybrid system.
      The Yeast 2-Hybrid experiments identified a strong and novel interaction between
      the transglutaminase moiety and protein kinase A anchor protein 13 (AKAP13),
      which was quantified by beta-galactosidase assay, confirmed in vitro by
      immunoprecipitation experiments using PC3 prostate cancer cell lysates, and in
      vivo colocalization was confirmed by immunofluorescence studies in PC3 cells.
      Because AKAP plays a major role in protein kinase A and Rho protein mediated
      signaling, functional studies are underway to elucidate the significance of tTG
      AKAP13 interaction in prostate cancer.

PMID- 16301119
TI  - Micro-array analysis of the effect of post-transurethral bladder tumor resection
      urine on transforming growth factor-beta1 dependent gene expression in
      transitional cell carcinoma.
AB  - INTRODUCTION AND OBJECTIVES: Prior studies have shown that bladder trauma
      occurring during transurethral bladder tumor resection increases urinary levels
      of the cytokine transforming growth factor (TGF)-beta1. This study used
      complementary deoxyribonucleic acid micro-array technology to identify additional
      genes in human transitional cell carcinoma (TCC), whose expression is altered as
      a consequence of increased urinary levels of TGF-beta1. METHODS: The human TCC
      line 253J was cultured in standard media, or media spiked with either 10% post
      transurethral bladder tumor resection urine (PTU), or PTU and anti-TGF-beta1
      neutralizing antibody. Messenger ribonucleic acid from these conditions, together
      with messenger ribonucleic acid from stably transfected 253J cells over
      expressing TGF-beta1, was hybridized with ATLAS micro-array membranes (Clontech,
      Palo Alto, CA) containing 588 human genes. Hybridization signal intensity was
      quantified using phospho-imaging. An analytic strategy based on the variance in
      the signal intensity ratio of specific housekeeping genes in control and
      experimental comparisons was used to identify significant changes in gene
      expression. Reverse transcriptase polymerase chain reaction of target genes was
      used to confirm gene over-expression and TGF-beta1 responsiveness. RESULTS: Seven
      genes were identified on micro-array: v-RAF-1, colony stimulating factor-1
      receptor, v-FGR, insulin growth factor-1 receptor, epidermal growth factor
      receptor, alpha5 integrin, and interferon receptor-1. Reverse transcriptase
      polymerase chain reaction confirmed over-expression in the autocrine TGF-beta1
      producing cell line and increased expression in response to exogenous TGF-beta1.
      CONCLUSIONS: TGF-beta1 in PTU alters the expression of multiple genes in human
      TCC in vitro. The impact of these changes on the biologic phenotype of the
      malignant cell and the efficacy of adjuvant therapies requires further
      evaluation.

PMID- 16301120
TI  - Prostatic extramedullary leukemia as a first site of relapse of acute
      nonlymphocytic leukemia.
AB  - Extramedullary leukemia (EML) is an uncommon clinical diagnosis in patients with
      acute nonlymphocytic leukemia (ANLL). Prostatic EML as a first site of ANLL
      relapse is even more rare. To our knowledge, only three cases have been reported.
      We describe an additional case of prostatic EML as a site of ANLL relapse. An
      asymptomatic male in ANLL remission was found to have a normal prostate-specific
      antigen (PSA) and a myeloid leukemic infiltrate in a newly diagnosed prostate
      nodule. Staging was negative for ANLL relapse. Local prostate radiation resolved
      the nodule, and the post-treatment needle biopsies were negative. He subsequently
      developed clinical relapse in bone marrow, blood, and small bowel and received
      salvage chemotherapy with mitoxantrone and etoposide.

PMID- 16301122
TI  - Pathologic findings and therapeutic outcome of desperation post-chemotherapy
      retroperitoneal lymph node dissection in advanced germ cell cancer.
AB  - Increased serum tumor markers after cisplatin-based chemotherapy have usually
      been considered a contraindication to surgery because of the presence of
      persistent active germ cell elements. However, a select population of patients
      with elevated serum tumor markers have undergone post-chemotherapy
      retroperitoneal lymph node dissection (RPLND) with curative intent. We evaluated
      the role of surgery to resect retroperitoneal-only marker positive tumor. Long
      term survival was observed in 50% of patients. Residual germ cell cancer was
      identified in 50% of patients, with a third alive at 5 years with no observed
      benefit from adjuvant chemotherapy. Select patients with increased tumor markers
      after chemotherapy are cured with surgery.

PMID- 16301123
TI  - Treatment of nonretroperitoneal residual germ cell tumor masses.
AB  - The appropriate treatment of residual disease outside the retroperitoneum after
      chemotherapy is a crucial component of the comprehensive approach to treating
      advanced testicular germ cell tumors (GCT). Residual nonretroperitoneal disease
      is most commonly found in the thorax but can also be identified in other sites,
      including the neck, liver, and brain. Although some data suggest that certain
      variables such as retroperitoneal lymph node dissection histology can accurately
      predict nonretroperitoneal histology, a multitude of studies show significant
      histologic discordance among different sites. Therefore, in patients with
      normalized serum tumor markers, we recommend resection of all sites of residual
      disease outside the retroperitoneum. Surgical approaches to the various lesions
      must minimize morbidity, and synchronous resections under the same anesthetic
      should be performed if technically feasible. After excision of residual viable
      GCT, evidence suggests that at least intermediate-risk patients who have received
      only induction chemotherapy will benefit from further systemic treatment.
      Patients with residual nonretroperitoneal viable GCT after salvage chemotherapy
      receive no benefit from additional systemic chemotherapy.

PMID- 16301124
TI  - Editorial comment on "Treatment of nonretroperitoneal residual germ cell tumor
      masses".

PMID- 16301125
TI  - Late relapse of testicular germ cell tumors.
AB  - The successful multidisciplinary approach for the management of germ cell tumors
      of the testis has resulted in survival rates of greater than 90% overall. While
      the majority of relapses in patients with germ cell tumors occur within the first
      2 years of treatment, the incidence of late relapse beyond 2 years has been
      increasing over recent years. The pattern of late relapse suggests that an
      inadequately controlled retroperitoneum is a major predisposing factor, with up
      to 80% of late relapses occurring in the retroperitoneum. These tumors tend to be
      chemorefractory and overall prognosis for patients with late relapse of germ cell
      tumors is relatively poor, with survival rates of approximately 30% to 40%. In
      this review, we present the recent data regarding the clinical presentation,
      patterns of relapse, histologic findings, appropriate treatment options, and
      outcomes for men with late relapse of germ cell tumors.

PMID- 16301126
TI  - Editorial comment on "Late relapse of testicular germ cell tumors".

PMID- 16301127
TI  - Complications of surgery and chemotherapy for testicular cancer.
AB  - Testicular cancer is a malignancy for which an interdisciplinary approach offers
      the highest likelihood of cure. In many patients, both chemotherapy and surgery
      play a prominent role in their care. Although cure can be achieved in a majority
      of patients, the treatment can occasionally leave the patient with late sequelae.
      This article discusses the long-term toxicity of curative surgical or cytotoxic
      therapy for germ cell tumors.

PMID- 16301128
TI  - Evolving strategies for renal tumor surgery: whether by open or by laparoscopic
      approaches, do the right operation!

PMID- 16301142
TI  - Intraosseous mucoepidermoid carcinoma of the maxilla in a teenager: a case report
      and review of literature.
AB  - Central mucoepidermoid carcinoma is a rare central bony lesion in teenagers. We
      report on an 11-year-old girl with a central pathologic lesion in the right
      hemimaxilla.

PMID- 16301143
TI  - A message from the ACOMS president.

PMID- 16301144
TI  - An evaluation of the clinical application of three different biodegradable
      osteosynthesis materials for the fixation of zygomatic fractures.
AB  - OBJECTIVE: The aim of this prospective study was to compare the clinical handling
      of 3 different biodegradable osteosynthesis materials and to determine whether
      they can be used for the fixation of all types of zygomatic fractures. STUDY
      DESIGN: A total of 54 consecutive patients who presented with displaced fractures
      of the zygomatic bone between October 2001 and May 2003 were randomly allocated
      to 3 biodegradable material groups for the fixation of the fractures. A titanium
      fixation system was used as rescue osteosynthesis whenever biodegradable
      materials failed. RESULTS: Seventy-one (75.5%) of 94 fracture sites were fixed
      with biodegradable osteosynthesis; 23 (24.5%) had to be fixed with titanium
      plates and screws. No statistically significant difference was found between the
      3 biodegradable materials with regard to their suitability for zygomatic fracture
      fixation (P = .16). Nonstable fixation (n = 7) or the need to fix small fragments
      (n = 16) were the reasons for using the titanium fixation system as rescue
      osteosynthesis at these sites. Biodegradable materials were most frequently
      unfeasible for use at the infraorbital rim and in the
      zygomaticomaxillary/anterior sinus wall area. CONCLUSIONS: It was possible to
      stabilize 3 of 4 zygomatic fractures with 1.5- or 1.7-mm biodegradable
      osteosynthesis. Insufficient fracture stabilization, especially at the
      infraorbital rim and the zygomaticomaxillary crest/anterior sinus wall, was the
      main reason to switch to titanium osteosynthesis. The biodegradable screw design
      is possibly too bulky for these particular bony structures.

PMID- 16301145
TI  - Fibula flap reconstruction of the condyle in disarticulation resections of the
      mandible: a case report and review of the technique.
AB  - Segmental resection of the mandible with disarticulation of the temporomandibular
      joint is occasionally required in the management of extensive tumors. The
      reconstruction of these deformities is complex, frequently involves staged
      procedures, and may result in significant deformity and loss of function for
      patients. The fibula free flap has become a standard treatment option for primary
      restoration of segmental mandibular deformities. However, little is published
      about its role in reconstructing the mandibular condyle. This paper describes a
      simplified technique for primary reconstruction of mandibular defects, including
      the mandibular condyle, in disarticulation resections of the mandible utilizing
      the fibula free flap.

PMID- 16301146
TI  - Early healing pattern of autogenous bone grafts with and without e-PTFE
      membranes: a histomorphometric study in rats.
AB  - OBJECTIVE: The aim of this study was to perform quantitative and qualitative
      analyses of the initial repair pattern of an autogenous bone block graft when
      covered or not with e-PTFE membranes. STUDY DESIGN: Sixty male Wistar rats
      received a bone graft plus an e-PTFE membrane (MB) or just the graft (B). A block
      graft was harvested from the animal's calvarium and was laid and stabilized on
      the external cortical area near the angle of the mandible. Descriptive histology
      and histomorphometric analyses were carried out and the data were analyzed
      statistically by ANOVA and the Tukey test, with the level of significance set at
      5%. RESULTS: The results for group B showed that there was bone loss during the
      healing period (B0 = 1.38, B45 = 1.05, F = 7.91 > F(C) = 3.02), that is, the
      initial volume of the graft decreased in time. Bone tissue loss was about 24%. In
      contrast, the MB group showed bone tissue gain along the observation period (MB0
      = 1.54, MB45 = 2.40, F = 7.91 > F(C) = 3.02), meaning that the total volume of
      newly formed bone was greater than the original graft area. Bone tissue gain was
      approximately 55%. MB showed significantly greater bone gain when compared to B
      (B45 = 1.05, MB45 = 2.40, F = 39.86 > F(C) = 1.90). These significant differences
      between B and MB could already be observed after 21 days. CONCLUSIONS: The bone
      block graft underwent resorption at an early healing stage, while additional new
      bone formation was observed when the bone graft was covered with an e-PTFE
      membrane.

PMID- 16301147
TI  - Expression of capsaicin receptor TRPV-1 in synovial tissues of patients with
      symptomatic internal derangement of the temporomandibular joint and joint pain.
AB  - OBJECTIVE: To elucidate expression of capsaicin receptor TRPV-1 in synovial
      tissues of the human temporomandibular joint (TMJ) with internal derangement and
      discuss its relationship with joint pain. STUDY DESIGN: Fifty-four TMJs in 54
      patients were examined using an immunohistochemical technique. As controls, 10
      TMJs with habitual dislocation without pain were also examined. RESULTS: TRPV-1
      was expressed mainly in the blood vessels beneath the lining cells in synovial
      tissues from 31 of the 54 joints with internal derangement and from 8 of the 10
      control joints. The extent score of TRPV-1-stained cells with internal
      derangement was not significantly higher than that of controls. The extent score
      of TRPV-1 showed no correlation with joint pain. CONCLUSIONS: TRPV-1 was detected
      in the region of the posterior disk attachment of synovial tissues from the TMJ
      in patients with internal derangement and controls. TRPV-1 may play a role in
      maintenance of the physiologic condition of the TMJ.

PMID- 16301148
TI  - Evaluation of oral and nasal halitosis parameters in patients with repaired cleft
      lip and/or palate.
AB  - OBJECTIVE: The objective of this study was to investigate the relationship
      between halitosis parameters in patients with and without cleft lip and/or
      palate. STUDY DESIGN: Forty-two subjects were examined. They were divided into
      group I, postgraduate students of Bauru Dental School (FOB); and group II,
      individuals with repaired cleft lip and/or palate. The concentration of volatile
      sulfur compounds (VSC) was assessed with a portable sulfide monitor and the
      values were correlated to the salivary flow rate and weight of tongue coating.
      RESULTS: There was a relationship between the presence of tongue coating and VSC
      levels, as well as between salivary flow rate and VSC levels in group II. The
      same group also revealed a significant correlation between weight of tongue
      coating and salivary flow rate. There were no significant differences between
      groups as regards the Halimeter oral measurement. CONCLUSIONS: Individuals with
      repaired cleft lip and/or palate can have the same VSC levels as subjects without
      clefts.

PMID- 16301149
TI  - Identification and treatment of scurvy: a case report.
AB  - Scurvy is a nondiscriminatory disease process resulting from a nutritional
      deficiency of ascorbic acid (vitamin C). The severe vitamin deficiency produces a
      breakdown in the cellular structure of the body. This case report describes a
      middle-age woman with a history of edema, bruising of the lower extremities,
      anemia, and severe periodontal disease. Her presentation and medical history are
      classic for the signs of scurvy. Scurvy is now only uncommonly seen in developed
      countries, but there are still vulnerable populations whose nutritional status
      can lead to scurvy. The aim of this report is to help the clinician identify and
      treat scurvy, a disease that was once feared for its high mortality but is now
      easily treatable, even in cases that have progressed to multiple organ
      dysfunction and failure.

PMID- 16301150
TI  - Treatment of severe temporomandibular joint clicking with botulinum toxin in the
      lateral pterygoid muscle in two cases of anterior disc displacement.
AB  - A novel treatment procedure is introduced for severe clicking of the
      temporomandibular joint (TMJ) associated with anterior disc displacement (ADD),
      using injections with botulinum toxin (BTX-A) in the lateral pterygoid muscle
      (LP). It has been suggested that ADD may be caused, precipitated, or maintained
      by LP activity, but the role of the LP in the dynamics of the TMJ clicking is
      uncertain. The case report includes 2 women, followed with clinical examinations,
      TMJ imaging, and electromyography (EMG), in whom local anesthetics in the LP
      could abolish the clicking for several days. BTX-A block of the LP (30 U Botox,
      given twice under EMG guidance with 6-month interval) temporarily reduced the
      action of the muscle, but the clicking was permanently eliminated and did not
      return during the observation period of 1 year, and a small but distinctive
      positional improvement in the disc-condyle relationship was obtained. However,
      the precise mechanisms behind the favourable treatment outcome are unclear.

PMID- 16301151
TI  - The effect of HAART on salivary microbiota in the Women's Interagency HIV Study
      (WIHS).
AB  - OBJECTIVE: Study the prevalence of potentially pathogenic microorganisms in
      saliva of HIV-positive women in the Women's Interagency HIV Study. STUDY DESIGN:
      157 HIV-positive and 31 HIV-negative women were studied. At baseline and every 6
      months over 4 years, information was collected on socioeconomic and educational
      status, oral and systemic health, including HIV markers and antiretroviral
      therapy, and frequency of professional oral care utilization. Bacterial and yeast
      pathogenic isolates from stimulated whole saliva were tentatively identified
      using standard methodologies. RESULTS: The prevalence of microorganisms in
      stimulated saliva of HIV-positive women was not significantly different from that
      of HIV-negative women. In HIV-positive women, highly active antiretroviral
      therapy (HAART) was independently and significantly associated with the presence
      of a variety of salivary bacterial species. HAART increased the risk for
      recovering Fusobacterium species (P < .001), enteric gram-negative rods (P <
      .05), Peptostreptococcus micros (P < .05), Campylobacter species (P < .0001),
      Eubacterium species (P < .001), and Tannerella forsythia (P < .01). In contrast,
      HAART led to decreased recovery rate of yeasts (Candida albicans and Candida
      dubliniensis) (P < .0001). CONCLUSION: The present findings suggest that the
      institution of HAART promotes an increasingly pathogenic salivary microbiota, at
      least temporarily. Similar findings have been reported for various nonoral
      microbial ecosystems.

PMID- 16301152
TI  - Papillon-Lefevre syndrome with albinism: a review of the literature and report of
      2 brothers.
AB  - BACKGROUND: Papillon-Lefevre syndrome (PLS) is a very rare autosomal recessive
      disorder characterized by palmoplantar hyperkeratosis and severe early onset of
      destructive periodontitis leading to premature loss of both primary and permanent
      dentitions. The etiopathogenesis of the condition suggests that there is a
      genetic basis for susceptibility to specific virulent pathogens. Variation in the
      clinical presentation of PLS has recently been observed. OBJECTIVE: The objective
      was to present the first report, which describes the concurrence of PLS and
      albinism. The etiology, pathology, and management of the condition were reviewed
      and genetic analysis was performed. SUBJECTS AND CLINICAL PRESENTATION: The
      probands are Jordanian brothers aged 13 and 20 years on their initial
      presentation. The parents were second cousins and not affected. The patients
      exhibited the typical clinical features of PLS with type 1 oculocutaneous
      albinism (OCA1). They also had increased susceptibility to infection manifested
      in recurrent tonsillitis, respiratory tract infection, pyoderma, onychogryphosis,
      and other pathosis. Skin biopsy demonstrated hyperkeratosis, focal parakeratosis,
      hypergranulosis, and acanthosis. Ectopic calcification of the dura was noticed in
      one of the probands. Hematological parameters tested were within the normal
      limits. The probands were tested for mutations in the causative genes of PLS and
      OCA1, cathepsin C (CTSC), and tyrosinase, respectively. Independent mutations
      (c.318-1G>A and c.817G>C/p.W272C) were identified in CTSC and tyrosinase,
      respectively. The probands were homozygous and their sister who had only PLS was
      homozygous for the same (CTSC) mutation but heterozygous for tyrosinase gene.
      CONCLUSION: We hope that this report of coinheritance PLS and albinism will
      initiate further investigations to disclose other possible variations that may
      enhance our knowledge on gene mutations of this intriguing syndrome.

PMID- 16301153
TI  - Epithelioid hemangioendothelioma of the oral cavity: report of two cases and
      review of the literature.
AB  - The epithelioid hemangioendothelioma is an uncommon vascular neoplasm of
      borderline or intermediate malignant potential. Although numerous sites of
      involvement are possible, these tumors most commonly arise in soft tissue, liver,
      and lung. Involvement of the oral cavity is rare. Only 12 cases of intraoral
      epithelioid hemangioendothelioma have been reported in the English language
      literature. We review the salient features of these previously reported cases and
      present 2 additional intraoral cases--one presenting as an asymptomatic
      radiolucency in the posterior mandible of a 23-year-old female, and the other
      presenting as an asymptomatic, erythematous to purplish gingival nodule in a 28
      year-old female. Intraoral tumors most commonly involve the gingival soft tissues
      and often are associated with adjacent alveolar bone resorption. Although it is
      not possible to estimate with accuracy the potential for recurrence and
      metastasis among intraoral tumors given the small number of previously reported
      cases, wide local excision with close clinical follow-up appears to be the
      treatment of choice for these tumors because of their unpredictable clinical
      behavior.

PMID- 16301154
TI  - Plasmablastic lymphoma of the oral cavity in an HIV-positive child.
AB  - A 7-year-old boy with a positive history of vertical HIV transmission presented
      with a painful swelling over the left upper jaw of 20 days' duration. A
      provisional diagnosis of non-Hodgkin's lymphoma or embryonal rhabdomyosarcoma was
      made. Fine-needle aspiration cytology findings were inconclusive, and incisional
      biopsy tissue on routine stains gave an impression of small round cell tumor with
      plasmacytoid features. A series of histochemical stains and immunohistochemical
      studies was carried out to differentiate and characterize this tumor. The salient
      immunostaining was negativity with all routine small round cell tumor markers and
      positivity with CD138 and lambda light chain restriction. The heterogeneous
      presentation of plasmablastic lymphoma as a variant of diffuse large B-cell
      lymphoma and its histogenesis is documented. Potential pitfalls and differential
      characterization of AIDS-plasmablastic lymphoma from other closely related tumors
      are addressed. The importance of excluding other common pediatric small round
      cell tumors by immunohistochemistry is highlighted. To the best of our knowledge,
      this is the first report of this entity in a vertically transmitted HIV-positive
      child.

PMID- 16301155
TI  - Submandibular gland mucocele: report of two cases.
AB  - Submandibular gland mucocele should be remembered in the differential diagnosis
      of swelling at the submandibular triangle. In the cystic lesion of the
      submandibular area, the biochemical analysis of aspirated material for amylase
      should be performed. The cases with submandibular gland mucocele should be
      treated by removing the lesion with both the submandibular and the sublingual
      glands.

PMID- 16301156
TI  - Clinical features of tricho-dento-osseous syndrome and presentation of three new
      cases: an addition to clinical heterogeneity.
AB  - OBJECTIVE: Tricho-dento-osseous dysplasia is a rare autosomal dominant disorder
      which involves increased bone density, enamel hypoplasia, enlarged pulp chambers,
      and molar taurodontism. This study discusses the phenotypic variability of this
      condition and describes 3 new cases from a large family. STUDY DESIGN: Three
      affected females and 1 unaffected female from the same family were clinically and
      radiographically evaluated. Mutation analysis was performed in the candidate gene
      DLX3. Phenotypes of affected individuals from 3 generations were compared to an
      unaffected control. RESULTS: All affected subjects show increased bone density in
      long bones and increased thickness and bone density in the skull, especially the
      skull base. Mandibles are within the upper normal size limits and display
      increased trabeculation and bone density. No bone loss or regression of the
      alveolar ridge occurs in older subjects after teeth have been lost. CONCLUSION:
      The mutation in DLX3 has positive effects on bone density throughout life.
      Although the mutation in this family is identical with mutations found in other
      families it results in clinical and phenotypic variability.

PMID- 16301157
TI  - Correlation of mandibular deviation with temporomandibular joint MR dimensions,
      MR disk position, and clinical symptoms.
AB  - OBJECTIVE: The objective of this study was to investigate the difference of the
      temporomandibular joint (TMJ) between deviated and nondeviated sides of the
      mandible in adult patients with mandibular deviation. STUDY DESIGN: TMJ size,
      disk displacement, and clinical symptoms of 28 patients were examined clinically
      and by magnetic resonance imaging (MRI). Twelve age- and sex-matched control
      subjects were also used to evaluate which side of the mandible in patients was
      similar to the control. RESULTS: The TMJ on the deviated side showed a smaller
      condyle and a higher incidence of disk displacement than the nondeviated side and
      those in the controls. However, the clinical symptoms showed no differences
      between the deviated and nondeviated sides, and no association with disk
      displacement. CONCLUSIONS: Our results suggest that the deviated side was the
      abnormal side and may have some association with mandibular deviation. However,
      the clinical symptoms could not indicate those differences.

PMID- 16301158
TI  - Quantitative analysis of errors in alveolar crest level caused by discrepant
      projection geometry in digital subtraction radiography: an in vivo study.
AB  - OBJECTIVE: This study compared the difference between 3 intraoral radiographic
      techniques on digital subtraction radiography (DSR) in vivo that are commonly
      used in a clinical setting. STUDY DESIGN: We evaluated and statistically analyzed
      the errors in the DSR image in 6 regions with 3 radiographic techniques:
      paralleling technique with a bite block attached to XCP, paralleling technique
      using XCP, and bisecting-angle technique. RESULTS: The amount of error using the
      bisecting-angle technique was too large for DSR, compared to that of the
      paralleling technique with a bite block attached to XCP. In the mandibular
      anterior region, the paralleling technique using XCP was not different from
      paralleling technique with a bite block attached to XCP. The lowest degree of
      error was present in the anterior region whereas the highest was present in the
      molar region. CONCLUSION: Bisecting-angle technique should be avoided, and
      paralleling technique using XCP can be used in the mandibular anterior region for
      DSR.

PMID- 16301159
TI  - Effectiveness of a calcium hydroxide and chlorhexidine digluconate mixture as
      disinfectant during retreatment of failed endodontic cases.
AB  - OBJECTIVE: The purpose of this in vivo investigation is to compare the effect of
      a slurry of Ca(OH)2 mixed in aqueous 2% chlorhexidine (CHX) versus aqueous
      Ca(OH)2 slurry alone on the disinfection of the pulp space of failed root-filled
      teeth during endodontic retreatment. STUDY DESIGN: Forty single-rooted previously
      root-filled teeth with associated periradicular lesions were included. The teeth
      were nonsurgically retreated and medicated over 3 treatment visits with 7-10-day
      intervals with either Ca(OH)2 in water or Ca(OH)2 in 2% aqueous CHX. Root canal
      cultures were collected in fluid thioglycollate, and bacterial growth was
      assessed by turbidity daily for 1 week, then weekly for an additional 3 weeks.
      The presence of enterococci in the root canals at the initial treatment session
      was determined. RESULTS: Of the total sample population, 12 of 40 (30%) were
      positive for bacteria before root filling. The control medication disinfected 12
      of 20 (60%) teeth including 2 of 4 teeth originally diagnosed with enterococci.
      The experimental medication resulted in disinfected 16 of 20 (80%) teeth at the
      beginning of the third appointment. None of the teeth originally containing
      enterococci showed remaining growth. This difference between the overall positive
      cultures was not statistically significant (P > .05). CONCLUSIONS: Canal dressing
      with a mixture of 2% CHX and Ca(OH)2 slurry is as efficacious as aqueous Ca(OH)2
      on the disinfection of failed root-filled teeth.

PMID- 16301160
TI  - Postoperative pain after root-end resection and filling.
AB  - OBJECTIVE: To evaluate the pain experience following root-end resection and
      filling with Mineral Trioxide Aggregate or Intermediate Restorative Material.
      STUDY DESIGN: Referred adult patients recruited using strict entry criteria were
      randomly allocated to receive either material. A standardized surgical technique
      was employed. Postoperative instructions and a pain questionnaire were given to
      each patient to record the severity of their pain at 3 time intervals-3-5 hours,
      24 hours, and 48 hours after surgery-on a standard visual analog scale (VAS).
      Patients were also asked to record consumption of any self-prescribed analgesics,
      the type, and dosage. RESULTS: At 3-5 hours after surgery, regardless of the
      material used, 90% of all patients experienced some level of postoperative pain.
      Twenty-four hours after surgery 82% of patients experienced pain, as did 72%
      after 48 hours. Thirty-seven percent of patients did not take any analgesics at
      all. In order of popularity, the analgesics taken were ibuprofen, acetaminophen,
      and acetaminophen plus codeine phosphate. The VAS measurements were reduced over
      time in both treatment groups (P < .001). There was no statistically significant
      difference in the proportion of subjects taking analgesics in each treatment
      group. Patients who used analgesics showed higher median VAS measurements at all
      time periods (P < .05). CONCLUSIONS: There was no significant difference in the
      pain experienced by both treatment groups. The postoperative pain was of a
      relatively short duration, at its maximum intensity early in the postoperative
      period but progressively decreased with time. Even if pain relief medication was
      needed, nonprescription analgesics were adequate and effective.

PMID- 16301161
TI  - Effects of intracanal carbon dioxide laser irradiation on cultured human
      fibroblasts.
AB  - OBJECTIVE: The purpose of this study was to evaluate, under various conditions,
      the damage that might occur to viable cells after CO2 laser irradiation of the
      root canal. STUDY DESIGN: A laser tip was placed within the root canal of
      extracted human teeth that were positioned above cultured fibroblasts (NB cells),
      and then irradiation was applied. The irradiation modes used were either pulse
      (40 pps) or super-pulse (151 pps). The laser energy was set at 32 J in both
      modes, and the tip of the laser beam was positioned to a point 2 mm from the
      fibroblasts. RESULTS: When the pulse mode irradiation was applied, there was
      significant difference (P < .05) in the percentage of viable cells between teeth
      with closed apical foramen (1-mm wall between root canal and root apex) and the
      #15 group (No. 15 K-file used), #30 group (No. 30 K-file), or #50 group (No. 50 K
      file). The difference between the #30 group and the #50 group (P < .05) was also
      significant. The larger the diameter of the apical foramen became, the lower was
      the percentage of viable cells. CONCLUSION: If a CO2 laser irradiates a root
      canal system enlarged to within 1 mm of the root canal length, little damage to
      the periapical tissues would be expected to occur.

PMID- 16301162
TI  - A case of multiple idiopathic external root resorption: a 6-year follow-up study.
AB  - Multiple idiopathic external root resorption of permanent teeth is a very
      infrequent phenomenon. This paper describes a case of multiple idiopathic
      external root resorption at cement-enamel junction in 21 of 25 teeth followed up
      for 6 years. In addition to clinical features and radiographs, we present results
      of histological and bacteriological examinations.

PMID- 16301163
TI  - Diagnosis and interpretation of injuries: a study of Dutch general practitioners.
AB  - This study explores the ability of Dutch general practitioners (GPs) in
      recognising types of injury. In the three sample cases, 48-91% classified the
      injury correctly. Only 9% of GPs recognised self-harm injury and in the 3rd case
      (child abuse) only 15% referred to the improbability of the account given. Only
      13% appeared able to assess two or three cases (almost) correctly. Recognition
      and description by Dutch GPs of these injuries is inadequate. This may have far
      reaching consequences for the victims. The increasing incidence of cases of
      violence demands that more attention should be paid to the issue during both
      basic and specialist medical training.

PMID- 16301164
TI  - Two of these or two of those?
AB  - Symmetrically dividing neuroepithelial cells may produce two daughters that are
      both proliferating or both postmitotic, as highlighted by Zigman et al. in this
      issue of Neuron and Sanada and Tsai in a recent issue of Cell. Here, I will
      attempt to offer a simple explanation why these results may be so different.

PMID- 16301165
TI  - Local axon guidance in cerebral cortex and thalamus: are we there yet?
AB  - Normal brain function requires the development of precise connections between
      thalamus and cerebral cortex. In this issue of Neuron, Cang et al. and Tori and
      Levitt argue that EphA/ephrin-A signaling in the target tissue guides sensory
      thalamic axons to the correct cortical area, and sensory cortical axons to
      precise thalamic targets. Although EphA/ephrin-A signaling organizes sensory maps
      within areas, and thalamocortical axons in the internal capsule, both papers
      argue that each developmental event is dissociable from the others.

PMID- 16301166
TI  - Origin and classification of neocortical interneurons.
AB  - Neocortical interneurons are very diverse in morphological, physiological,
      molecular, and developmental characteristics. Recent work is discovering strong
      correlations between these phenotypic features, confirming the intuition of Cajal
      and Lorente that distinct classes of interneurons exist, each presumably
      mediating a different circuit function. A paper by Butt et al. in this issue of
      Neuron describes correlations between the developmental origin of interneurons
      and their anatomical, electrophysiological, and molecular properties. An effort
      to standardize the nomenclature of interneurons is underway. Because different
      interneuron subtypes have different ontogenic origin, they could be classified
      based on their developmental specification by transcription factors.

PMID- 16301167
TI  - A rose by any other code.
AB  - In this issue of Neuron, Mazor and Laurent demonstrate that the internal
      representation of an odor in the antennal lobe of locusts is broadly distributed
      across the population of projection neurons and is formatted in a manner that
      requires deciphering of response transients rather than steady-state activity
      patterns.

PMID- 16301168
TI  - Cortical map reorganization without cholinergic modulation.
AB  - Acetylcholine has been shown to modulate many forms of cortical plasticity. New
      evidence indicates that reorganization of adult primary auditory cortex is still
      possible after removal of cholinergic inputs. This finding suggests that
      acetylcholine may act less as a gate and more as a gain control on cortical
      plasticity.

PMID- 16301169
TI  - Come together, right...now: synchronization of rhythms in a mammalian circadian
      clock.
AB  - In mammals, the suprachiasmatic nuclei (SCN) of the hypothalamus act as a
      dominant circadian pacemaker, coordinating rhythms throughout the body and
      regulating daily and seasonal changes in physiology and behavior. This review
      focuses on the mechanisms that mediate synchronization of circadian rhythms
      between SCN neurons. Understanding how these neurons communicate as a network of
      circadian oscillators has begun to shed light on the adaptability and dysfunction
      of the brain's master clock.

PMID- 16301170
TI  - Searching for "the top" in top-down control.
AB  - Although numerous theoretical models implicate the prefrontal cortex (PFC) as a
      source of top-down control signals, empirical support is limited. In this review,
      we highlight direct evidence for this view of PFC function and discuss several
      lines of other supportive findings. Most evidence to-date is only suggestive due
      to methodological challenges in tracking the spatiotemporal dynamics of cortical
      networks. However, we discuss several promising approaches that could further our
      understanding of the role of the PFC in goal-directed behavior.

PMID- 16301171
TI  - Mammalian inscuteable regulates spindle orientation and cell fate in the
      developing retina.
AB  - During mammalian neurogenesis, progenitor cells can divide with the mitotic
      spindle oriented parallel or perpendicular to the surface of the neuroepithelium.
      Perpendicular divisions are more likely to be asymmetric and generate one
      progenitor and one neuronal precursor. Whether the orientation of the mitotic
      spindle actually determines their asymmetric outcome is unclear. Here, we
      characterize a mammalian homolog of Inscuteable (mInsc), a key regulator of
      spindle orientation in Drosophila. mInsc is expressed temporally and spatially in
      a manner that suggests a role in orienting the mitotic spindle in the developing
      nervous system. Using retroviral RNAi in rat retinal explants, we show that
      downregulation of mInsc inhibits vertical divisions. This results in enhanced
      proliferation, consistent with a higher frequency of symmetric divisions
      generating two proliferating cells. Our results suggest that the orientation of
      neural progenitor divisions is important for cell fate specification in the
      retina and determines their symmetric or asymmetric outcome.

PMID- 16301172
TI  - Autonomous function of synaptotagmin 1 in triggering synchronous release
      independent of asynchronous release.
AB  - Ca(2+) triggers neurotransmitter release in at least two principal modes,
      synchronous and asynchronous release. Synaptotagmin 1 functions as a Ca(2+)
      sensor for synchronous release, but its role in asynchronous release remains
      unclear. We now show that in cultured cortical neurons stimulated at low
      frequency (<or.1 Hz), deletion of synaptotagmin 1 blocks synchronous GABA and
      glutamate release without significantly increasing asynchronous release. At
      higher stimulation frequencies (>or Hz), deletion of synaptotagmin 1 also alters
      only synchronous, not asynchronous, release during the stimulus train, but
      dramatically enhances "delayed asynchronous release" following the stimulus
      train. Thus synaptotagmin 1 functions as an autonomous Ca(2+) sensor independent
      of asynchronous release during isolated action potentials and action potential
      trains, but restricts asynchronous release induced by residual Ca(2+) after
      action potential trains. We propose that synaptotagmin 1 occupies release "slots"
      at the active zone, possibly in a Ca(2+)-independent complex with SNARE proteins
      that are freed when action potential-induced Ca(2+) influx activates
      synaptotagmin 1.

PMID- 16301173
TI  - Encoding light intensity by the cone photoreceptor synapse.
AB  - How cone synapses encode light intensity determines the precision of information
      transmission at the first synapse on the visual pathway. Although it is known
      that cone photoreceptors hyperpolarize to light over 4-5 log units of intensity,
      the relationship between light intensity and transmitter release at the cone
      synapse has not been determined. Here, we use two-photon microscopy to visualize
      release of the synaptic vesicle dye FM1-43 from cone terminals in the intact
      lizard retina, in response to different stimulus light intensities. We then
      employ electron microscopy to translate these measurements into vesicle release
      rates. We find that from darkness to bright light, release decreases from 49 to
      approximately 2 vesicles per 200 ms; therefore, cones compress their 10,000-fold
      operating range for phototransduction into a 25-fold range for synaptic vesicle
      release. Tonic release encodes ten distinguishable intensity levels, skewed to
      most finely represent bright light, assuming release obeys Poisson statistics.

PMID- 16301174
TI  - Dissociation of corticothalamic and thalamocortical axon targeting by an EphA7
      mediated mechanism.
AB  - Molecular mechanisms generating the topographic organization of corticothalamic
      (CT) circuits, which comprise more than three-quarters of the synaptic inputs
      onto sensory relay neurons, and their interdependence with thalamocortical (TC)
      axon development are unknown. Using in utero electroporation-mediated gene
      transfer, we show that EphA7-mediated signaling on neocortical axons controls the
      within-nucleus topography of CT projections in the thalamus. Notably, CT axons
      that mis-express EphA7 do not shift the relative positioning of their pathway
      within the subcortical telencephalon (ST), indicating that they do not depend
      upon EphA7/ephrin-A signaling in the ST for establishing this topography.
      Moreover, mis-expression of cortical EphA7 results in disrupted topography of CT
      projections, but unchanged inter- and intra-areal topography of TC projections.
      Our results support a model in which EphA/ephrin-A signaling controls
      independently the precision with which CT and TC projections develop, yet is
      essential for establishing their topographic reciprocity.

PMID- 16301175
TI  - Ephrin-as guide the formation of functional maps in the visual cortex.
AB  - Ephrin-As and their receptors, EphAs, are expressed in the developing cortex
      where they may act to organize thalamic inputs. Here, we map the visual cortex
      (V1) in mice deficient for ephrin-A2, -A3, and -A5 functionally, using intrinsic
      signal optical imaging and microelectrode recording, and structurally, by
      anatomical tracing of thalamocortical projections. V1 is shifted medially,
      rotated, and compressed and its internal organization is degraded. Expressing
      ephrin-A5 ectopically by in utero electroporation in the lateral cortex shifts
      the map of V1 medially, and expression within V1 disrupts its internal
      organization. These findings indicate that interactions between gradients of
      EphA/ephrin-A in the cortex guide map formation, but that factors other than
      redundant ephrin-As are responsible for the remnant map. Together with earlier
      work on the retinogeniculate map, the current findings show that the same
      molecular interactions may operate at successive stages of the visual pathway to
      organize maps.

PMID- 16301176
TI  - The temporal and spatial origins of cortical interneurons predict their
      physiological subtype.
AB  - Interneurons of the cerebral cortex represent a heterogeneous population of cells
      with important roles in network function. At present, little is known about how
      these neurons are specified in the developing telencephalon. To explore whether
      this diversity is established in the early progenitor populations, we conducted
      in utero fate-mapping of the mouse medial and caudal ganglionic eminences (MGE
      and CGE, respectively), from which most cortical interneurons arise. Mature
      interneuron subtypes were assessed by electrophysiological and immunological
      analysis, as well as by morphological reconstruction. At E13.5, the MGE gives
      rise to fast-spiking (FS) interneurons, whereas the CGE generates predominantly
      regular-spiking interneurons (RSNP). Later at E15.5, the CGE produces RSNP
      classes distinct from those generated from the E13.5 CGE. Thus, we provide
      evidence that the spatial and temporal origin of interneuron precursors in the
      developing telencephalic eminences predicts the intrinsic physiological
      properties of mature interneurons.

PMID- 16301177
TI  - Activity-dependent dendritic spine structural plasticity is regulated by small
      GTPase Rap1 and its target AF-6.
AB  - Activity-dependent remodeling of dendritic spines is essential for neural circuit
      development and synaptic plasticity, but the mechanisms that coordinate synaptic
      structural and functional plasticity are not well understood. Here we investigate
      the signaling pathways that enable excitatory synapses to undergo activity
      dependent structural modifications. We report that activation of NMDA receptors
      in cultured cortical neurons induces spine morphogenesis and activation of the
      small GTPase Rap1. Rap1 bimodally regulates spine morphology: activated Rap1
      recruits the PDZ domain-containing protein AF-6 to the plasma membrane and
      induces spine neck elongation, while inactive Rap1 dissociates AF-6 from the
      membrane and induces spine enlargement. Rap1 also regulates spine content of AMPA
      receptors: thin spines induced by Rap1 activation have reduced GluR1-containing
      AMPA receptor content, while large spines induced by Rap1 inactivation are rich
      in AMPA receptors. These results identify a signaling pathway that regulates
      activity-dependent synaptic structural plasticity and coordinates it with
      functional plasticity.

PMID- 16301178
TI  - Sorting of vesicular monoamine transporter 2 to the regulated secretory pathway
      confers the somatodendritic exocytosis of monoamines.
AB  - The release of monoamine neurotransmitters from cell bodies and dendrites has an
      important role in behavior, but the mechanism (vesicular or non vesicular) has
      remained unclear. Because the location of vesicular monoamine transporter 2
      (VMAT2) defines the secretory vesicles capable of monoamine release, we have
      studied its trafficking to assess the potential for monoamine release by
      exocytosis. In neuroendocrine PC12 cells, VMAT2 localizes exclusively to large
      dense-core vesicles (LDCVs), and we now show that cytoplasmic signals target
      VMAT2 directly to LDCVs within the biosynthetic pathway. In neurons, VMAT2
      localizes to a population of vesicles that we now find undergo regulated
      exocytosis in dendrites. Although hippocampal neurons do not express typical LDCV
      proteins, transfected chromogranins A, B, and brain-derived neurotrophic factor
      (BDNF) colocalize with VMAT2. VMAT2 thus defines a population of secretory
      vesicles that mediate the activity-dependent somatodendritic release of multiple
      retrograde signals involved in synaptic function, growth, and plasticity.

PMID- 16301179
TI  - Coupling between NMDA receptor and acid-sensing ion channel contributes to
      ischemic neuronal death.
AB  - Acid-sensing ion channels (ASICs) composed of ASIC1a subunit exhibit a high
      Ca(2+) permeability and play important roles in synaptic plasticity and acid
      induced cell death. Here, we show that ischemia enhances ASIC currents through
      the phosphorylation at Ser478 and Ser479 of ASIC1a, leading to exacerbated
      ischemic cell death. The phosphorylation is catalyzed by Ca(2+)/calmodulin
      dependent protein kinase II (CaMKII) activity, as a result of activation of NR2B
      containing N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) during
      ischemia. Furthermore, NR2B-specific antagonist, CaMKII inhibitor, or
      overexpression of mutated form of ASIC1a with Ser478 or Ser479 replaced by
      alanine (ASIC1a-S478A, ASIC1a-S479A) in cultured hippocampal neurons prevented
      ischemia-induced enhancement of ASIC currents, cytoplasmic Ca(2+) elevation, as
      well as neuronal death. Thus, NMDAR-CaMKII cascade is functionally coupled to
      ASICs and contributes to acidotoxicity during ischemia. Specific blockade of
      NMDAR/CaMKII-ASIC coupling may reduce neuronal death after ischemia and other
      pathological conditions involving excessive glutamate release and acidosis.

PMID- 16301180
TI  - Endocannabinoids control the induction of cerebellar LTD.
AB  - The long-term depression (LTD) of parallel fiber (PF) synapses onto Purkinje
      cells plays a central role in motor learning. Endocannabinoid release and LTD
      induction both depend upon activation of the metabotropic glutamate receptor
      mGluR1, require postsynaptic calcium increases, are synapse specific, and have a
      similar dependence on the associative activation of PF and climbing fiber
      synapses. These similarities suggest that endocannabinoid release could account
      for many features of cerebellar LTD. Here we show that LTD induction is blocked
      by a cannabinoid receptor (CB1R) antagonist, by inhibiting the synthesis of the
      endocannabinoid 2-arachidonyl glycerol (2-AG), and is absent in mice lacking the
      CB1R. Although CB1Rs are prominently expressed presynaptically at PF synapses,
      LTD is expressed postsynaptically. In contrast, a previously described transient
      form of inhibition mediated by endocannabinoids is expressed presynaptically.
      This indicates that Purkinje cells release 2-AG that activates CB1Rs to both
      transiently inhibit release and induce a postsynaptic form of LTD.

PMID- 16301181
TI  - Transient dynamics versus fixed points in odor representations by locust antennal
      lobe projection neurons.
AB  - Projection neurons (PNs) in the locust antennal lobe exhibit odor-specific
      dynamic responses. We studied a PN population, stimulated with five odorants and
      pulse durations between 0.3 and 10 s. Odor representations were characterized as
      time series of vectors of PN activity, constructed from the firing rates of all
      PNs in successive 50 ms time bins. Odor representations by the PN population can
      be described as trajectories in PN state space with three main phases: an on
      transient, lasting 1-2 s; a fixed point, stable for at least 8 s; and an off
      transient, lasting a few seconds as activity returns to baseline. Whereas all
      three phases are odor specific, optimal stimulus separation occurred during the
      transients rather than the fixed points. In addition, the PNs' own target neurons
      respond least when their PN-population input stabilized at a fixed point. Steady
      state measures of activity thus seem inappropriate to understand the neural code
      in this system.

PMID- 16301182
TI  - Basal forebrain cholinergic input is not essential for lesion-induced plasticity
      in mature auditory cortex.
AB  - The putative role of the basal forebrain cholinergic system in mediating lesion
      induced plasticity in topographic cortical representations was investigated.
      Cholinergic immunolesions were combined with unilateral restricted cochlear
      lesions in adult cats, demonstrating the consequence of cholinergic depletion on
      lesion-induced plasticity in primary auditory cortex (AI). Immunolesions almost
      eliminated the cholinergic input to AI, while cochlear lesions produced broad
      high-frequency hearing losses. The results demonstrate that the near elimination
      of cholinergic input does not disrupt reorganization of the tonotopic
      representation of the lesioned (contralateral) cochlea in AI and does not affect
      the normal representation of the unlesioned (ipsilateral) cochlea. It is
      concluded that cholinergic basal forebrain input to AI is not essential for the
      occurrence of lesion-induced plasticity in AI.

PMID- 16301183
TI  - Human dorsal and ventral auditory streams subserve rehearsal-based and echoic
      processes during verbal working memory.
AB  - To hear a sequence of words and repeat them requires sensory-motor processing and
      something more-temporary storage. We investigated neural mechanisms of verbal
      memory by using fMRI and a task designed to tease apart perceptually based
      ("echoic") memory from phonological-articulatory memory. Sets of two- or three
      word pairs were presented bimodally, followed by a cue indicating from which
      modality (auditory or visual) items were to be retrieved and rehearsed over a
      delay. Although delay-period activation in the planum temporale (PT) was
      insensible to the source modality and showed sustained delay-period activity, the
      superior temporal gyrus (STG) activated more vigorously when the retrieved items
      had arrived to the auditory modality and showed transient delay-period activity.
      Functional connectivity analysis revealed two topographically distinct fronto
      temporal circuits, with STG co-activating more strongly with ventrolateral
      prefrontal cortex and PT co-activating more strongly with dorsolateral prefrontal
      cortex. These argue for separate contributions of ventral and dorsal auditory
      streams in verbal working memory.

PMID- 16301185
TI  - How many people develop fractures with what outcome?
AB  - Osteoporosis is an important clinical and public health problem because of its
      association with fractures. Osteoporotic fractures result in significant
      morbidity, mortality and health and social care costs. Hip fracture is the major
      adverse health consequence associated with the disease, although other fractures
      are also linked with significant adverse outcomes. Because of current demographic
      trends, the number of men and women with osteoporosis and osteoporotic fractures
      is set to increase dramatically over the next 50 years unless effective
      preventive measures are adopted. Over and above this demographic trend there is
      evidence that the age-specific rates of fractures have increased during the last
      century. This chapter reviews the epidemiology of osteoporotic fractures,
      including their occurrence, descriptive epidemiology and impact.

PMID- 16301186
TI  - Determinants of skeletal fragility.
AB  - Strategies to reduce fracture risk must be based on a sound understanding of the
      mechanisms that underline the increased incidence of fractures with age and with
      certain diseases. There is evidence that in addition to bone minerals density,
      other factors influence bone strength. The chapter reviews the biomechanical
      aspects of age-related fractures, including the interacting roles of traumatic
      loading and bone strength, and the factors that determine a bones resistances to
      fracture. Also discussed are the mechanisms by which anti-catabolic and anabolic
      therapies for osteoporosis may affect bone strength. Finally, several current and
      future methodologies for improving assessment of bone strength in patients are
      evaluated.

PMID- 16301187
TI  - What is the role of falls?
AB  - There is now firm evidence to support interventions in the prevention of falls in
      older people, and emerging data support prevention of falls as a method of
      fracture prevention. This chapter discusses the epidemiology of falls, risk
      factors associated with an increased risk of falling, assessment of the older
      faller, and evidence-based approaches to the prevention of falls in the older
      person. Several randomized controlled trials have found that hip protectors, if
      worn, probably prevent hip fractures, but that poor compliance is a major issue
      limiting the effectiveness of this form of intervention. More data are needed to
      support the role of prevention of falls in preventing fractures, as well as
      comparative cost-effectiveness data with other evidence-based approaches to
      preventing fractures in an older population.

PMID- 16301188
TI  - Assessment of fracture risk: who should be treated for osteoporosis?
AB  - The clinical significance of osteoporosis arises from the fractures that occur.
      Of these, the hip fracture in particular is associated with high morbidity,
      mortality and socio-economic costs. The primary goal of osteoporosis treatment is
      fracture prevention. In this chapter we try to answer the question of how to
      assess fracture risk and how to identify those above a given risk threshold so
      that treatment can be given to those in whom fractures can be prevented (cost-)
      effectively. At first, the two main strategies for fracture prevention-
      population screening and case finding--are discussed. Then a fracture risk
      assessment score, based on easily identifiable clinical risk factors, is
      proposed. This clinical risk factor analysis can guide the decisions whether
      additional bone assessment is relevant and whether treatment should be started.
      Finally, we advocate that absolute fracture risk is important for communication
      with the patient about the decision whether or not to initiate treatment.

PMID- 16301189
TI  - What is the role of DXA, QUS and bone markers in fracture prediction, treatment
      allocation and monitoring?
AB  - There is evidence that treatment can decrease the risk of fractures in
      osteoporotic patients, and screening of these patients is therefore relevant.
      Diagnosis of osteoporosis is based on the T-score calculated from bone mineral
      density (BMD) measurements. BMD measurements have been widely used for the
      management of osteoporosis, and a low BMD is a strong risk factor for fractures.
      But BMD measurement has several limitations in both diagnosis, prediction of
      fracture risk, and treatment follow-up. Quantitative ultrasound (QUS) parameters,
      an alternative to BMD in the assessment of bone, are independent risk factors for
      osteoporotic fracture. However, the use of QUS cannot be recommended for both
      allocation and monitoring of treatment. Biochemical markers of bone remodelling
      can be useful for both prediction of fracture risk and monitoring of treatment if
      sources of variability are controlled.

PMID- 16301190
TI  - Who will benefit from antiresorptive treatment (bisphosphonates)?
AB  - Bisphosphonates are very effective treatments of postmenopausal osteoporosis.
      They suppress bone turnover, increase bone mineral density (BMD), and maintain or
      improve structural and material properties of bone, thereby decreasing the risk
      of fractures. All patients selected for treatment according to current
      international guidelines can benefit from bisphosphonate therapy independently of
      their prevalent rate of bone turnover. Long-term extensions (up to 10 years) of
      pivotal clinical trials with daily bisphosphonate administration showed sustained
      efficacy with no evidence of adverse effects on bone metabolism and skeletal
      fragility. Recent studies focus on the resolution of the effects of
      bisphosphonates on bone metabolism and fracture risk following cessation of long
      term treatment. Such studies may help to formulate treatment recommendations
      according to the risk of the individual patient.

PMID- 16301191
TI  - Who will benefit from treatment with selective estrogen receptor modulators
      (SERMs)?
AB  - Clinical trials have demonstrated that the selective estrogen receptor modulator
      raloxifene can reduce the risk of vertebral fracture, but have not unequivocally
      demonstrated an effect on non-vertebral fracture. Consequently it is recommended
      that raloxifene be used mainly in postmenopausal women with milder osteoporosis
      as a preventive measure or for treatment in those with predominantly spinal
      osteoporosis. Since the effects of raloxifene on bone mineral density and bone
      turnover may reverse soon after cessation, it is recommended that raloxifene be
      used as long-term therapy for 5-10 years. Because of its quicker offset, use of
      raloxifene may have advantages over potent bisphosphonates if use of anabolic
      agents are contemplated in an individual patient.

PMID- 16301192
TI  - Newer drug treatments: their effects on fracture prevention.
AB  - Drug treatment of osteoporosis is based on the knowledge of mechanisms of bone
      turnover and the manipulation of the cellular components of bone turnover in
      terms of recruitment, activation and apoptosis of the cells involved. Based on
      their mechanisms of action, drugs used in the treatment of osteoporosis can be
      divided into those that inhibit bone turnover (bisphosphonates, SERMs,
      calcitonin), those that stimulate bone turnover (parathyroid hormone), and those
      with mixed effects (strontium ranelate). In this chapter we discuss the anti
      fracture effects of some newer drugs together with innovative aspects of intake
      (monthly oral intake for ibandronate) or mechanisms of action (parathyroid
      hormone and strontium ranelate). Some new drugs that are being studied for their
      potential anti-fracture effects are listed.

PMID- 16301193
TI  - How to manage osteoporosis in children.
AB  - Osteoporosis is increasingly being seen in young people. The primitive forms are
      relatively rare, but the secondary forms--particularly in long-term
      corticosteroid therapy--are a relevant problem given the much longer survival in
      chronic diseases such as cystic fibrosis, chronic renal insufficiency, leukaemia,
      and Duchenne muscular dystrophy. Controlled, prospective studies to evaluate the
      results of prevention and therapy in children are still lacking. The basis of
      therapy is the correct daily intake of calcium and the use of vitamin D (or
      active metabolites). This helps the growing skeleton to restore its equilibrium
      in many cases. Restraining the long-term use of corticosteroids to the minimum
      effective dose and shorter duration is essential. In severe cases, particularly
      in the presence of fractures, bisphosphonates can be remarkably effective. In
      some cases, such as idiopathic juvenile osteoporosis, the rule is spontaneous
      resolution, and the advisability of an aggressive drug therapy is discussed.

PMID- 16301194
TI  - How to manage osteoporosis after the menopause.
AB  - Many women seek advice about bone health at the time of the menopause. Although
      fracture probability is low in the majority, treatment may be cost-effective if
      targeted at those at highest risk. Optimal selection of individuals for
      intervention is based on a case-finding approach, fracture probability being
      estimated using a combination of bone mineral density and clinical risk factors.
      A variety of therapeutic interventions is available for the prevention of
      osteoporotic fractures in postmenopausal women. Hormone replacement therapy (HRT)
      is a second-line option in most, although it has a place in the management of
      perimenopausal women with menopausal symptoms who are at risk from fracture and
      in other postmenopausal women who express a preference for HRT over other
      options, after being fully informed about known risks and benefits.

PMID- 16301195
TI  - The management of secondary osteoporosis.
AB  - Secondary osteoporosis is common among patients being evaluated for osteoporosis.
      All men and premenopausal women with unexplained bone loss or a history of a
      fragility fracture should undergo a work-up for secondary osteoporosis. Also,
      postmenopausal women with risk factors for secondary osteoporosis should be
      carefully evaluated. The evaluation should include a thorough history, physical
      examination, bone mineral density testing, and laboratory testing. While there is
      no consensus for a cost-effective laboratory evaluation, some recommendations
      include: 25-hydroxyvitamin D, parathyroid hormone (PTH), serum and urine calcium,
      phosphate, creatinine, liver function tests, a complete blood count, testosterone
      in men, and thyroid-stimulating hormone. After a thorough review of the
      evaluation for secondary osteoporosis, this chapter reviews the pathophysiology
      and treatment of secondary osteoporotic disorders, including vitamin D
      insufficiency, osteomalacia, the osteoporosis of erosive inflammatory arthritis,
      ankylosing spondylitis, systemic lupus erythematosus, and osteoporosis related to
      anti-androgenic therapy for prostate cancer and aromatase inhibitor therapy for
      breast cancer. Physicians have a significant responsibility to evaluate and treat
      the underlying medical problem that is the cause of secondary osteoporosis and to
      optimize bone health in the individual patient.

PMID- 16301196
TI  - In whom and how to prevent glucocorticoid-induced osteoporosis.
AB  - Glucocorticoid use is widespread in medicine. While it is often life-saving, side
      effects are well known. The most common side-effect is osteoporosis. Today we
      have therapies with proven efficacy for the prevention of vertebral fractures and
      bone loss. Consequently recognition of glucocorticoid-induced osteoporosis is
      extremely important given the availability of effective therapy.

PMID- 16301197
TI  - Bone loss in inflammatory arthritis: mechanisms and therapeutic approaches with
      bisphosphonates.
AB  - The inflammatory process in rheumatoid arthritis provokes intense bone
      resorption, evidenced as bone erosions, juxta-articular osteopenia and
      generalized osteoporosis. These types of bone loss share a common pathogenesis,
      and the role of osteoclasts in focal bone erosion was verified in elegant animal
      studies. The tumour necrosis factor (TNF) family of cytokines and receptors-
      specifically TNF-alpha, RANKL, RANK and OPG--are dominant regulators of
      osteoclastic bone resorption in rheumatoid arthritis. The confirmation of the
      osteoclast mechanism provides new insight into the structural joint protection
      afforded by disease-modifying drugs and suggests innovative approaches to limit
      bone destruction. Emerging treatment strategies for bone disease in rheumatoid
      arthritis are the use of monoclonal antibodies to neutralize RANKL, and powerful
      bisphosphonates that target pathogenic osteoclasts.

PMID- 16301198
TI  - Setting up an osteoporosis fracture liaison service: background and potential
      outcomes.
AB  - A large evidence base now exists for treatment interventions that will reduce
      fracture risk. However, the key area of practice now is how to get this evidence
      base into clinical practice. All health-care systems are subject to financial
      constraints, and therefore it is important that all areas of clinical practice
      can demonstrate that they are able to deliver care in a cost-effective manner. It
      has become increasingly recognized within the area of osteoporosis that treatment
      interventions should be targeted at patients at the highest absolute risk of
      fracture in order to maximize the cost-effectiveness of the service. One key
      subgroup of patients who are at higher absolute fracture risk are patients who
      present with an incident fracture. Although it has long been recognized that this
      is a key group to be considered for investigation and intervention, it is also
      clear that any form of structured care for this group has not been developed.
      This chapter will review the background and practical aspects of running a
      fracture liaison service. This service addresses the issue of secondary
      prevention of fracture while also considering both the absolute risk of fracture
      and the absolute benefit of the intervention. Issues relating to the background
      evidence base underpinning the service as well as the practical issues relating
      to the actual running of a service are discussed. Some of the potential service
      outcomes are also reviewed.

PMID- 16301200
TI  - Food, toys, and love: pediatric palliative care.

PMID- 16301202
TI  - 'Protein Peeling': an approach for splitting a 3D protein structure into compact
      fragments.
AB  - MOTIVATION: The object of this study is to propose a new method to identify small
      compact units that compose protein three-dimensional structures. These fragments,
      called 'protein units (PU)', are a new level of description to well understand
      and analyze the organization of protein structures. The method only works from
      the contact probability matrix, i.e. the inter Calpha-distances translated into
      probabilities. It uses the principle of conventional hierarchical clustering,
      leading to a series of nested partitions of the 3D structure. Every step aims at
      dividing optimally a unit into 2 or 3 subunits according to a criterion called
      'partition index' assessing the structural independence of the subunits newly
      defined. Moreover, an entropy-derived squared correlation R is used for assessing
      globally the protein structure dissection. The method is compared to other
      splitting algorithms and shows relevant performance. AVAILABILITY: An Internet
      server with dedicated tools is available at http://www.ebgm.jussieu.fr/~gelly/

PMID- 16301203
TI  - Accurate anchoring alignment of divergent sequences.
AB  - MOTIVATION: Obtaining high quality alignments of divergent homologous sequences
      for cross-species sequence comparison remains a challenge. RESULTS: We propose a
      novel pairwise sequence alignment algorithm, ACANA (ACcurate ANchoring
      Alignment), for aligning biological sequences at both local and global levels.
      Like many fast heuristic methods, ACANA uses an anchoring strategy. However,
      unlike others, ACANA uses a Smith-Waterman-like dynamic programming algorithm to
      recursively identify near-optimal regions as anchors for a global alignment.
      Performance evaluations using a simulated benchmark dataset and real promoter
      sequences suggest that ACANA is accurate and consistent, especially for divergent
      sequences. Specifically, we use a simulated benchmark dataset to show that ACANA
      has the highest sensitivity to align constrained functional sites compared to
      BLASTZ, CHAOS and DIALIGN for local alignment and compared to AVID, ClustalW,
      DIALIGN and LAGAN for global alignment. Applied to 6007 pairs of human-mouse
      orthologous promoter sequences, ACANA identified the largest number of conserved
      regions (defined as over 70% identity over 100 bp) compared to AVID, ClustalW,
      DIALIGN and LAGAN. In addition, the average length of conserved region identified
      by ACANA was the longest. Thus, we suggest that ACANA is a useful tool for
      identifying functional elements in cross-species sequence analysis, such as
      predicting transcription factor binding sites in non-coding DNA. AVAILABILITY:
      ACANA software and test sequence data are publicly available at
      http://BioMedEmpire.org/

PMID- 16301204
TI  - The SWISS-MODEL workspace: a web-based environment for protein structure homology
      modelling.
AB  - MOTIVATION: Homology models of proteins are of great interest for planning and
      analysing biological experiments when no experimental three-dimensional
      structures are available. Building homology models requires specialized programs
      and up-to-date sequence and structural databases. Integrating all required tools,
      programs and databases into a single web-based workspace facilitates access to
      homology modelling from a computer with web connection without the need of
      downloading and installing large program packages and databases. RESULTS: SWISS
      MODEL workspace is a web-based integrated service dedicated to protein structure
      homology modelling. It assists and guides the user in building protein homology
      models at different levels of complexity. A personal working environment is
      provided for each user where several modelling projects can be carried out in
      parallel. Protein sequence and structure databases necessary for modelling are
      accessible from the workspace and are updated in regular intervals. Tools for
      template selection, model building and structure quality evaluation can be
      invoked from within the workspace. Workflow and usage of the workspace are
      illustrated by modelling human Cyclin A1 and human Transmembrane Protease 3.
      AVAILABILITY: The SWISS-MODEL workspace can be accessed freely at
      http://swissmodel.expasy.org/workspace/

PMID- 16301205
TI  - Inferring functional information from domain co-evolution.
AB  - MOTIVATION: Co-evolution is a powerful mechanism for understanding protein
      function. Prior work in this area has shown that co-evolving proteins are more
      likely to share the same function than those that do not because of functional
      constraints. Many of the efforts founded on this observation, however, are at the
      level of entire sequences, implicitly assuming that the complete protein sequence
      follows a single evolutionary trajectory. Since it is well known that a domain
      can exist in various contexts, this assumption is not valid for numerous multi
      domain proteins. Motivated by these observations, we introduce a novel technique
      called Coevolutionary-Matrix that captures co-evolution between regions of two
      proteins. Instead of using existing domain information, the method exploits
      residue-level conservation to identify co-evolving regions that might correspond
      to domains. RESULTS: We show that the Coevolutionary-Matrix method can detect
      greater number of known functional associations for the Escherichia coli proteins
      when compared with earlier implementations of phylogenetic profiles. Furthermore,
      co-evolving regions of proteins detected by our method enable us to make
      hypotheses about their specific functions, many of which are supported by
      existing biochemical studies.

PMID- 16301206
TI  - A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues
      myonephropathic metabolic syndrome in severe hindlimb ischemia.
AB  - The therapeutic use of angiogenic factors shows promise in the treatment of
      critical limb ischemia; however, its potential for myonephropathic metabolic
      syndrome (MNMS), a fatal complication caused by arterial reconstruction, has not
      been elucidated. The objective of this study was to evaluate the effectiveness of
      recombinant Sendai virus-mediated gene transfer of fibroblast growth factor-2
      (FGF-2) directly compared with that of a radical scavenger, MCI-186, in a rat
      model of MNMS. MNMS was surgically induced by aortic occlusion below renal
      arteries for 4 h, followed by 6 h of reperfusion. Administration of MCI-186
      (twice; iv 5 min before induced ischemia and ip 5 min before reperfusion; 10
      mg/kg, respectively), but not FGF-2 gene transfer (once, 48 h before induced
      ischemia), dramatically prevented the increase of serum biochemical markers as
      well as the edema of the gastrocnemius muscle. The effect of MCI-186 was
      accompanied by the marked suppression of the neutrophilic infiltration into the
      local (muscle) and remote (lung) organs. Although serum and muscular levels of a
      neutrophil-chemoattractant (growth-related oncogene/cytokine-induced neutrophil
      chemoattractant-1) were not affected by any treatment, the serum level of soluble
      intercellular adhesion molecule-1 was decreased by treatment with MCI-186 but not
      by treatment with FGF-2. These results suggest the distinct mechanism of MNMS
      from critical limb ischemia without reperfusion. Therefore, radical scavenging
      should be paid more attention than therapeutic angiogenesis when arterial
      circulation is reconstructed.

PMID- 16301207
TI  - Documenting the effectiveness of an educational tool and group discussion for
      understanding the cardiovascular adjustments to upright posture.

PMID- 16301208
TI  - Jehovah's Witnesses in A&E.

PMID- 16301209
TI  - Constructing the parental linkage phase and the genetic map over distances <1 cM
      using pooled haploid DNA.
AB  - A new statistical approach for construction of the genetic linkage map and
      estimation of the parental linkage phase based on allele frequency data from
      pooled gametic (sperm or egg) samples is introduced. This method can be applied
      for estimation of recombination fractions (over distances <1 cM) and ordering of
      large numbers (even hundreds) of closely linked markers. This method should be
      extremely useful in species with a long generation interval and a large genome
      size such as in dairy cattle or in forest trees; the conifer species have haploid
      tissues available in megagametophytes. According to Mendelian expectation, two
      parental alleles should occur in gametes in 1:1 proportions, if segregation
      distortion does not occur. However, due to mere sampling variation, the observed
      proportions may deviate from their expected value in practice. These deviations
      and their dependence along the chromosome can provide information on the parental
      linkage phase and on the genetic linkage map. Usefulness of the method is
      illustrated with simulations. The role of segregation distortion as a source of
      these deviations is also discussed. The software implementing this method is
      freely available for research purposes from the authors.

PMID- 16301210
TI  - Change in the redox state of glutathione regulates differentiation of tracheary
      elements in Zinnia cells and Arabidopsis roots.
AB  - Exogenously applied GSH and GSSG can control the in vitro differentiation of
      mesophyll cells to tracheary elements (TEs) in Zinnia elegans, and de novo GSH
      synthesis is essential for the early differentiation. The purpose of the present
      study is to address how GSH and GSSG control TE differentiation. GSSG transiently
      accumulated during the in vitro TE differentiation and exogenously applied GSSG
      down-regulated transcript levels of GSSG reductase (GR), an enzyme maintaining
      glutathione in a reduced redox state, while there were no significant changes in
      transcript levels of enzymes involved in GSH synthesis. Transgenic Arabidopsis
      overexpressing the GR gene showed delayed TE formation in the root, which was
      attributed to the suppression of cell division. Exogenously applied GSH had an
      effect similar to overexpression of the GR gene. These findings suggest that
      reduced states of glutathione suppress TE differentiation. In wild-type
      Arabidopsis, TE formation was promoted by application of GSSG at an appropriate
      concentration, but was suppressed at higher concentrations. A T-DNA-inserted
      knockout mutant of cytosolic GR exhibited delayed TE formation; this phenotype
      was little affected by GSSG application. Taken together, the process of the redox
      changes in glutathione is considered to be controlled via GR activity for TE
      differentiation.

PMID- 16301211
TI  - Differential phosphoprotein labeling (DIPPL), a method for comparing live cell
      phosphoproteomes using simultaneous analysis of (33)P- and (32)P-labeled
      proteins.
AB  - We developed a differential method to reveal kinase-specific phosphorylation
      events in live cells. In this method, cells in which the specified kinase is
      inactive are labeled with (32)Pi, whereas cells in which the kinase is active are
      labeled with (33)Pi. The two cell extracts are then mixed, and proteins are
      separated on a single two-dimensional gel. The dried gel is exposed twice. The
      first exposure reveals both (32)P- and (33)P-labeled proteins; the kinase
      specific spots are revealed because of (33)P labeling. The second exposure is
      conducted with two acetate sheets intervening between the gel and the detection
      plate. This maneuver screens out the less energetic (33)P-labeled proteins while
      allowing the more energetic (32)P-labeled proteins to be detected, thus leaving
      only those spots that were phosphorylated independently of the specified kinase.
      We demonstrate the utility of this method for detecting kinase substrates in rare
      tissue by focusing on extracellular signal-regulated kinase-specific
      phosphorylation of stathmin/OP18 in primary rat sympathetic neurons.

PMID- 16301213
TI  - Mapping common regulatory variants to human haplotypes.
AB  - Inter-individual variation in gene expression has proven to be in part governed
      by genetic determinants, which may be trans- or cis-acting. The underlying cause
      of cis-acting regulatory variation has been identified in only a handful of the
      hundreds of genes shown to display differential allelic expression. In this
      report, we describe a systematic effort to map common cis-acting variants in 64
      genes, using association methods in HapMap samples. We identified 16 loci (25%),
      each of which harbors common haplotypes that affect total expression of a gene,
      and a further 17 loci (27%) with evidence of haplotypes affecting relative
      allelic expression in heterozygote samples. Our survey suggests that detailed
      mapping of allele-specific in vivo expression will provide a rich source of
      regulatory SNPs or haplotypes that should be given high priority in association
      studies of human phenotypes.

PMID- 16301212
TI  - Loss of polycystin-1 or polycystin-2 results in dysregulated apolipoprotein
      expression in murine tissues via alterations in nuclear hormone receptors.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations of
      PKD1 and PKD2. Murine gene targeting studies have shown that these genes play an
      essential role in development, with homozygous inactivation resulting in
      embryonic lethality. Recently, Pkd1-/- lethality has been linked to placental
      insufficiency. In this study, the placenta was used as a model to identify
      factors involved in these developmental abnormalities. Microarray analysis of
      Pkd1-/- placentae showed upregulation of a set of apolipoprotein-related genes.
      These changes were validated and were found to be associated with increased
      quantities of apolipoproteins in the amniotic fluid. Increased apolipoprotein
      gene expression was also observed in Pkd2-/-placentae and in cystic kidneys of
      Pkd1cond/-; Meox2cre/+ mice. Using chromatin immunoprecipitation assays, we
      determined that the activity of HNF-4alpha, a major regulator of apolipoprotein
      gene expression, was also increased in these organs. These findings suggest a
      potential role for dysregulation of nuclear hormone receptors in the pathogenesis
      of ADPKD.

PMID- 16301214
TI  - Meta-analysis of genome-wide linkage studies for quantitative lipid traits in
      African Americans.
AB  - Genetic influences on lipid traits have been suggested by numerous studies. In
      addition to heritability studies, over 50 genome scans have been performed to
      identify regions of linkage for quantitative lipid levels. Five of these scans
      have been performed in African Americans (four univariate and one bivariate
      linkage analysis), but with results that have been largely inconclusive. Linkage
      analyses are often limited by both sample size and heterogeneity, which may lead
      to nominal LOD scores or lack of evidence for linkage; the use of meta-analysis
      to combine linkage results from populations with similar ethnic backgrounds may
      help overcome some of these limitations. Thus, we performed a meta-analysis using
      data from four genome scans conducted in African American families to identify
      chromosomal regions showing evidence of linkage for total cholesterol (TC),
      triglycerides (TG), low density lipoprotein cholesterol (LDL) and high density
      lipoprotein cholesterol (HDL). Significant evidence (i.e. P<0.00042) for linkage
      was found for LDL on chromosome 1q32.1-q41 (Pweighted=0.00014 and
      Punweighted=0.00007) and 1q41-q44 (Pweighted=0.00017 and Punweighted=0.00014). We
      found suggestive evidence (i.e. P<0.00847) for TG on 16p12.1-q11.2 and for HDL on
      4p15.1-p11. We also assessed heterogeneity between studies and found significant
      evidence for low heterogeneity for both regions on chromosome 1q (P=0.0300 and
      P=0.0279, respectively) for LDL and chromosome 16 (P=0.0429) for TG.
      Statistically significant evidence for linkage and low heterogeneity on
      chromosome 1q therefore suggest that this region may harbor a gene underlying the
      inheritance of LDL in African Americans.

PMID- 16301215
TI  - T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and
      stimulates lactase promoter activity in vitro.
AB  - Two phenotypes exist in the human population with regard to expression of lactase
      in adults. Lactase non-persistence (adult-type hypolactasia and lactose
      intolerance) is characterized by a decline in the expression of lactase-phlorizin
      hydrolase (LPH) after weaning. In contrast, lactase-persistent individuals have a
      high LPH throughout their lifespan. Lactase persistence and non-persistence are
      associated with a T/C polymorphism at position -13,910 upstream the lactase gene.
      A nuclear factor binds more strongly to the T-13,910 variant associated with
      lactase persistence than the C-13,910 variant associated with lactase non
      persistence. Oct-1 and glyceraldehyde-3-phosphate dehydrogenase were co-purified
      by DNA affinity purification using the sequence of the T-13,910 variant.
      Supershift analyses show that Oct-1 binds directly to the T-13,910 variant, and
      we suggest that GAPDH is co-purified due to interactions with Oct-1. Expression
      of Oct-1 stimulates reporter gene expression from the T and the C-13,910
      variant/LPH promoter constructs only when it is co-expressed with HNF1alpha.
      Binding sites for other intestinal transcription factors (GATA-6, HNF4alpha, Fox
      and Cdx-2) were identified in the region of the -13,910 T/C polymorphism. Three
      of these sites are required for the enhancer activity of the -13,910 region. The
      data suggest that the binding of Oct-1 to the T-13,910 variant directs increased
      lactase promoter activity and this might provide an explanation for the lactase
      persistence phenotype in the human population.

PMID- 16301216
TI  - Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome
      type 1 and type 2.
AB  - Usher syndrome (USH) is the most frequent cause of combined deaf-blindness in
      man. USH is clinically and genetically heterogeneous with at least 11 chromosomal
      loci assigned to the three USH types (USH1A-G, USH2A-C, USH3A). Although the
      different USH types exhibit almost the same phenotype in human, the identified
      USH genes encode for proteins which belong to very different protein classes and
      families. We and others recently reported that the scaffold protein harmonin
      (USH1C-gene product) integrates all identified USH1 molecules in a USH1-protein
      network. Here, we investigated the relationship between the USH2 molecules and
      this USH1-protein network. We show a molecular interaction between the scaffold
      protein harmonin (USH1C) and the USH2A protein, VLGR1 (USH2C) and the candidate
      for USH2B, NBC3. We pinpoint these interactions to interactions between the PDZ1
      domain of harmonin and the PDZ-binding motifs at the C-termini of the USH2
      proteins and NBC3. We demonstrate that USH2A, VLGR1 and NBC3 are co-expressed
      with the USH1-protein harmonin in the synaptic terminals of both retinal
      photoreceptors and inner ear hair cells. In hair cells, these USH proteins are
      also localized in the signal uptaking stereocilia. Our data indicate that the
      USH2 proteins and NBC3 are further partners in the supramolecular USH-protein
      network in the retina and inner ear which shed new light on the function of USH2
      proteins and the entire USH-protein network. These findings provide first
      evidence for a molecular linkage between the pathophysiology in USH1 and USH2.
      The organization of USH molecules in a mutual 'interactome' related to the
      disease can explain the common phenotype in USH.

PMID- 16301217
TI  - Usherin, the defective protein in Usher syndrome type IIA, is likely to be a
      component of interstereocilia ankle links in the inner ear sensory cells.
AB  - Usher syndrome type IIa (USH2A) combines moderate to severe congenital hearing
      impairment and retinitis pigmentosa. It is the most common genetic form of USH.
      USH2A encodes usherin, which was previously defined as a basement membrane
      protein. A much larger USH2A transcript predicted to encode a transmembrane (TM)
      isoform was recently reported. Here, we address the role of TM usherin in the
      inner ear. Analysis of the usherin alternative transcripts in the murine inner
      ear revealed the existence of several predicted TM usherin isoforms with modular
      ectodomains of different lengths. In addition, we identified in the usherin
      cytoplasmic region a predicted 24 amino acid peptide, derived from a newly
      defined exon that is predominantly expressed in the inner ear but not in the
      retina. In mouse and rat inner ears, we show that TM usherin is present at the
      base of the differentiating stereocilia, which make up the mechanosensitive hair
      bundles receptive to sound. The usherin immunolabeling is transient in the hair
      bundles of cochlear hair cells (HCs), but persists in mature hair bundles of
      vestibular HCs. Several lines of evidence support the involvement of TM usherin
      in the composition of the ankle links, a subset of filamentous lateral links
      connecting stereocilia at the base. By co-immunoprecipitation and in vitro
      binding assays, we establish that the usherin cytodomain can bind to whirlin and
      harmonin, two PDZ domain-containing proteins that are defective in genetic forms
      of isolated deafness and USH type I, respectively. These PDZ proteins are
      suitable to provide the anchoring of interstereocilia lateral links to the F
      actin core of stereocilia. Our results strongly suggest that congenital deafness
      in USH type I and type II shares similar pathogenic mechanisms, i.e. the
      disruption of hair bundle links-mediated adhesion forces that are essential for
      the proper organization of growing hair bundles.

PMID- 16301218
TI  - Deletion of the ANKRD15 gene at 9p24.3 causes parent-of-origin-dependent
      inheritance of familial cerebral palsy.
AB  - A four-generation family was studied in which nine children had congenital
      cerebral palsy (CP), characterized by quadriplegia and mental retardation. All
      the affected children were born to healthy, related fathers, whereas the children
      of their healthy female relatives were unaffected. Linkage analysis attributed
      the condition to chromosome 9p24.3, where a 225 kb deletion was identified. The
      deletion spans a single gene, ANKRD15 (ankyrin repeat domain 15), which is
      ubiquitously expressed. In the affected children, the ANKRD15 is not expressed in
      lymphoblastoid cells, whereas in their healthy fathers, who harbor the same
      deletion, the expression of ANKRD15 did not deviate from controls. This
      expression pattern can be interpreted as a maternal imprinted gene that is
      expressed only from the paternal allele. The expression of ANKRD15 in
      lymphoblastoid cells from the control group was monoallelic but not imprinted.
      The monoallelic expression was restricted to the ANKRD15 gene, whereas biallelic
      expression was found in the DOCK8 gene, which resides at the telomeric side of
      the deletion. No correlation was found between the expression of the ANKRD15 gene
      and the pattern of DNA methylation in the CpG islands 5' of the gene. However,
      differences in methylation pattern were found in the CpG islands flanking the
      DMRT1 gene, which is located at the 3' side of the ANKRD15 gene. In the affected
      individuals, as in the control group, the CpG islands were hypo-methylated,
      whereas in the healthy fathers, the CpG islands were hyper-methylated in cis with
      the deletion. This unique family demonstrates a phenomenon of a deletion that
      creates imprinting-like inheritance. The implication of this family to sporadic
      CP is discussed.

PMID- 16301221
TI  - Increasing heart size and age attenuate anesthetic preconditioning in guinea pig
      isolated hearts.
AB  - Anesthetic preconditioning (APC) reduces myocardial ischemia/reperfusion injury.
      Recent investigations have reported that older hearts are not susceptible to APC.
      We investigated if increasing heart size with age determines the susceptibility
      to APC in young guinea pigs. Langendorff-prepared guinea pig hearts of different
      weights (1.1-2.2 g) and ages (2-7 wks) were exposed to 1.3 mM sevoflurane for 15
      min followed by 30 min washout (APC; n = 20) before 30 min global ischemia and
      120 min reperfusion. Control hearts (n = 20) were not subject to APC. Left
      ventricular pressure was measured isovolumetrically and infarct size was
      determined by triphenyltetrazolium staining. Functional data were not different
      between groups at the beginning of the experiments nor did they correlate with
      heart weight or age. At 120 min reperfusion, left ventricular pressure, coronary
      flow, and tissue viability showed significant negative correlations with
      increasing heart weight and age in APC but not in control hearts; i.e., APC
      improved function and attenuated infarct size better in smaller/younger hearts
      than in larger/older hearts. Thus, increasing age and heart size attenuate the
      susceptibility for APC even in younger guinea pigs. This may have important
      implications for further basic science research and the possible clinical
      applicability of APC in humans.

PMID- 16301222
TI  - Ischemic preconditioning improves energy state and transplantation survival in
      obese Zucker rat livers.
AB  - Livers from obese donors often have fatty infiltrates and are more susceptible to
      ischemia-reperfusion injury and subsequent graft dysfunction. This often leads to
      the exclusion of organs from obese donors. We investigated whether ischemic
      preconditioning (IP, 10 min ischemia, 10 min reperfusion) preserves cellular
      metabolism in livers from obese Zucker rats during cold ischemia. Liver samples (
      IP and +IP) were collected from obese and control lean rats at different time
      points of cold ischemia (CI) and analyzed by magnetic resonance spectroscopy (1H-
      and 31P-MRS) to assess whether IP improves hepatic cellular metabolism. IP
      significantly improved high energy metabolism in IP livers from obese rats when
      compared with obese controls during the first hours of CI. At 4 h of cold
      storage, obese IP livers were not different from control lean non-IP livers. The
      beneficial metabolic effect of IP on livers form obese rats, however, was absent
      at 8 h of reperfusion. In contrast, in livers from lean rats, IP resulted in
      improved high-energy metabolism during the entire observation period of 8 h. In a
      later part of the study, IP of liver grafts from obese rats before 4 h of cold
      storage improved recipient survival after graft transplantation. IP of liver
      grafts from obese rats before 4 h of CI increases 24-h survival of recipient
      animals from 25% to 88%.

PMID- 16301223
TI  - Isoflurane protects renal function against ischemia and reperfusion through
      inhibition of protein kinases, JNK and ERK.
AB  - Isoflurane has a pharmacological preconditioning effect against ischemia in the
      heart and brain, but whether this also occurs in the kidney is unclear. In this
      study, we investigated pharmacological preconditioning by isoflurane in the rat
      kidney. In the isoflurane preconditioning group (1.5% isoflurane for 20 min
      before renal ischemia) serum creatinine (1.2 +/- 0.7 and 1.1 +/- 0.2 mg/dL) and
      blood urea nitrogen (99 +/- 29 and 187 +/- 31 mg/dL) were significantly smaller
      at 24 and 48 h after reperfusion than in the nonpreconditioning group
      (creatinine; 2.4 +/- 1.2 and 2.9 +/- 0.9 mg/dL, urea; 62 +/- 19 and 79 +/- 20
      mg/dL). We also investigated the intracellular signal transduction involved in
      isoflurane preconditioning in the kidney. The activities of the stress protein
      kinases, JNK and ERK but not p38, were significantly less in the kidneys of the
      preconditioning group than in those of the nonpreconditioning group (P < 0.05).
      We conclude that isoflurane has a preconditioning effect against renal
      ischemia/reperfusion injury when administered before ischemia. Inhibition of the
      protein kinases, JNK and ERK, might be involved in the mechanisms of isoflurane
      preconditioning.

PMID- 16301224
TI  - Inhibition of mitochondrial permeability transition enhances isoflurane-induced
      cardioprotection during early reperfusion: the role of mitochondrial KATP
      channels.
AB  - Inhibition of the mitochondrial permeability transition pore (mPTP) mediates the
      protective effects of brief, repetitive ischemic episodes during early
      reperfusion after prolonged coronary artery occlusion. Brief exposure to
      isoflurane immediately before and during early reperfusion also produces
      cardioprotection, but whether mPTP is involved in this beneficial effect is
      unknown. We tested the hypothesis that mPTP mediates isoflurane-induced
      postconditioning and also examined the role of mitochondrial KATP (mKATP)
      channels in this process. Rabbits (n = 102) subjected to a 30-min coronary
      occlusion followed by 3 h reperfusion received 0.9% saline (control), isoflurane
      (0.5 or 1.0 MAC) administered for 3 min before and 2 min after reperfusion, or
      the mPTP inhibitor cyclosporin A (CsA, 5 or 10 mg/kg) in the presence or absence
      of the mPTP opener atractyloside (5 mg/kg) or the selective mK(ATP) channel
      antagonist 5-hydroxydecanoate (5-HD; 10 mg/kg). Other rabbits received 0.5 MAC
      isoflurane plus 5 mg/kg CsA in the presence and absence of atractyloside or 5-HD.
      Isoflurane (1.0 but not 0.5 MAC) and CsA (10 but not 5 mg/kg) reduced (P < 0.05)
      infarct size (21% +/- 4%, 44% +/- 6%, 24% +/- 3%, and 43% +/- 6%, respectively,
      mean +/- sd of left ventricular area at risk; triphenyltetrazolium staining) as
      compared with control (42% +/- 7%). Isoflurane (0.5 MAC) plus CsA (5 mg/kg) was
      also protective (27% +/- 4%). Neither atractyloside nor 5-HD alone affected
      infarct size, but these drugs abolished protection by 1.0 MAC isoflurane, 10
      mg/kg CsA, and 0.5 MAC isoflurane plus 5 mg/kg CsA. The results indicate that
      mPTP inhibition enhances, whereas opening abolishes, isoflurane-induced
      postconditioning. This isoflurane-induced inhibition of mitochondrial
      permeability transition is dependent on activation of mitochondrial KATP channels
      in vivo.

PMID- 16301225
TI  - Cardiac output measurement using the transesophageal Doppler method is less
      accurate than the thermodilution method when changing PaCO2.
AB  - Cardiac output (CO) determination using transesophageal Doppler is based on the
      measurement of descending aortic blood flow. Because cerebral blood flow is
      dependent on PaCO2, an increase in PaCO2 would result in an increase of CO
      because of the increase in cerebral blood flow and vice versa. We enrolled 30
      patients undergoing off-pump coronary artery graft surgery in the study. The CO
      was determined by both transesophageal Doppler and thermodilution while PaCO2 was
      maintained at either 30 mmHg or 40 mmHg in random order. The CO by thermodilution
      was significantly higher at PaCO2 of 40 mmHg (4.17 +/- 0.94 L/min) than at 30
      mmHg (3.78 +/- 0.85 L/min). On the other hand, there were no significant
      differences in CO by transesophageal Doppler: 3.85 +/- 0.76 L/min at PaCO2 of 40
      mmHg and 3.77 +/- 0.74 at 30 mmHg. Bland-Altman analysis yielded bias and
      precision of -0.32 and 0.49 L/min at PaCO2 of 40 mmHg, and -0.01 and 0.34 L/min
      at 30 mmHg. These results indicate that both methods of CO measurement are in
      agreement at 30 mmHg of PaCO2, but the thermodilution method provides higher
      values at 40 mmHg of PaCO2.

PMID- 16301226
TI  - Aprotinin in major orthopedic surgery: a systematic review of randomized
      controlled trials.
AB  - Aprotinin therapy is a promising strategy for reducing blood loss and blood
      transfusion requirements. The efficacy and safety of aprotinin in orthopedic
      surgery, however, remain controversial. We searched electronic databases for
      randomized controlled trials on the efficacy and safety of the use of aprotinin
      in orthopedic surgery. Thirteen trials that included a total of 506 patients who
      underwent major orthopedic surgery were analyzed. The pooled intraoperative and
      perioperative blood loss was significantly less in the aprotinin-treated patients
      than in the control patients (weighted mean difference [WMD] for intraoperative
      blood loss = -229 mL, 95% confidence interval [CI] = -367 to -91 mL, P = 0.0011;
      WMD for perioperative blood loss = -557 mL; 95% CI = -860 to -254 mL; P <
      0.0001). The pooled amounts of red blood cell (RBC) units (U) transfused
      intraoperatively and perioperatively were significantly less in the aprotinin
      treated patients than in the control patients (WMD for intraoperative RBC U = 
      1.1 U; 95% CI = -1.7 to -0.4 U; P = 0.0001; WMD for perioperative RBC U = -1.1 U;
      95% CI = -1.7 to -0.5 U; P < 0.0001). Aprotinin was not associated with an
      increased incidence of deep vein thrombosis (odds ratio = 0.39; 95% CI = 0.14 to
      1.05, P = 0.061). The authors conclude that aprotinin reduces the intraoperative
      and perioperative blood loss and allogeneic blood transfusion requirement and may
      not be associated with increased risk of deep vein thrombosis in the presence of
      pharmacological or mechanical prophylaxis in patients undergoing major orthopedic
      surgery.

PMID- 16301227
TI  - Four cases of cardiopulmonary thromboembolism during liver transplantation
      without the use of antifibrinolytic drugs.
AB  - Orthotopic liver transplantation (OLT) is one of the most demanding surgical
      procedures performed. Intraoperative bleeding can be substantial and related to
      both surgical and nonsurgical causes. A less common but previously reported
      phenomenon is intraoperative cardiopulmonary thromboembolism precipitating major
      patient morbidity and mortality. In this paper, we present four cases of
      intraoperative thromboembolism during OLT. These cases were performed without the
      concomitant use of antifibrinolytic drugs. We performed a review and analysis of
      previously reported cases of intraoperative thromboembolism during OLT. Possible
      causes of thromboembolism, clinical management, use of thromboelastography, and
      the role of antifibrinolytic drugs are discussed.

PMID- 16301228
TI  - Parachute mitral valve.

PMID- 16301229
TI  - Airway protective reflexes evoked by laryngeal instillation of distilled water
      under sevoflurane general anesthesia in children.
AB  - To investigate how sevoflurane modifies airway protective reflexes in
      anesthetized children, we recruited patients younger than 12-yr-old for our
      study. Anesthesia was induced with inhaled sevoflurane in oxygen. The airway was
      managed with a laryngeal mask airway and the patient breathing spontaneously.
      Depending on the depth of anesthesia, the subjects were divided into two groups:
      Group 1 and Group 2 (1% and 2% of end-tidal sevoflurane concentration,
      respectively). Behaviors of the larynx were assessed mainly by the fiberscopic
      images of the larynx as well as respiratory flow and esophageal pressure. A small
      dose, 0.02 mL/kg of distilled water (minimum 0.2 mL) was instilled to the larynx
      through a channel of the scope to evoke an airway protective reflex from the
      larynx. The responses were categorized into passive (laryngeal closure,
      laryngospasm, and apnea) and active (cough, expiration reflex, and swallowing
      reflex) responses. Ten subjects were included in each group. In both groups, the
      primary responses were passive; however, in Group 1, active reflexes were also
      observed in 8 of 10 subjects; no subjects in Group 2 had active reflexes (P <
      0.01). We concluded that, in children, the depth of general anesthesia with
      sevoflurane modified airway protective reflexes.

PMID- 16301230
TI  - Clonidine treatment for agitation in children after sevoflurane anesthesia.
AB  - Clonidine is effective in treating sevoflurane-induced postanesthesia agitation
      in children. We conducted a study on 169 children to quantify the risk reduction
      of clonidine agitation in patients admitted to our day-surgery pediatric clinic.
      Children were randomly allocated to receive clonidine 2 mug/kg or placebo before
      general anesthesia with sevoflurane that was also supplemented with a regional or
      central block. An observer blinded to the anesthetic technique assessed recovery
      variables and the presence of agitation. Pain and discomfort scores were
      significantly decreased in the clonidine group; the incidence of agitation was
      reduced by 57% (P = 0.029) and the incidence of severe agitation by 67% (P =
      0.064). Relative risks for developing agitation and severe agitation were 0.43
      (95% confidence interval, 0.24-0.78) and 0.32 (0.09-1.17), respectively.
      Clonidine produces a substantial reduction in the risk of postsevoflurane
      agitation in children.

PMID- 16301231
TI  - The safety of patient-controlled analgesia by proxy in pediatric oncology
      patients.
AB  - Between February 1999 and December 2003, we studied the use of patient-controlled
      analgesia (PCA) to control pain in 1011 children and young adults with cancer, by
      evaluating 4972 24-h periods of PCA usage, 576 of which involved PCA by proxy.
      Selection of patients for PCA by proxy was based on younger age group,
      neuromuscular limitation, expectation of repeated painful procedures, and
      terminal disease. We measured the incidence of respiratory and neurological
      complications related to the use of PCA. Major complications were observed during
      70 of the 4972 24-h observations, with 28 of 4972, or 0.56%, involving
      respiratory complications, 35 of 4972, or 0.7%, involving neurological
      complications, and 7 of 4972 24-h observations, or 0.14%, involving both
      respiratory and neurological complications. In the PCA by proxy group two
      respiratory complications, two neurological complications and one mixed
      respiratory and neurological complication were observed [corrected] Reversal of
      opioid-related respiratory or neurological effects with naloxone was required in
      three instances, two in the standard PCA group and one in the PCA by proxy group.
      Recommendations to ensure continuing safety include careful patient selection,
      education of proxy users, appropriate documentation, and institutional
      guidelines.

PMID- 16301232
TI  - Aortic valve repair in a patient with congenital afibrinogenemia.
AB  - We describe the management of cardiopulmonary bypass (CPB) in a patient with
      congenital afibrinogenemia (AF). Although this state is akin to the state after
      hirudin administration, where CPB has been successfully performed, heparinization
      is still essential to preserve other clotting factors and prevent excessive
      bleeding. Aprotinin further helps in preservation of clotting factors. There are
      case reports of thrombosis associated with AF, but aprotinin can be safely used
      because it is, by definition, an anticoagulant. Cryoprecipitate effectively
      restores the fibrinogen and produces normal clotting.

PMID- 16301233
TI  - Is regional anesthesia really better than general anesthesia?

PMID- 16301234
TI  - A comparison of regional versus general anesthesia for ambulatory anesthesia: a
      meta-analysis of randomized controlled trials.
AB  - Both regional anesthesia and general anesthesia have been proposed to provide
      optimal ambulatory anesthesia. We searched MEDLINE and other databases for
      randomized controlled trials comparing regional anesthesia and general anesthesia
      in ambulatory surgery patients for meta-analysis. Only major conduction blocks
      were considered to be regional anesthesia. Regional anesthesia was further
      separated into central neuraxial block and peripheral nerve block. Fifteen (1003
      patients) and 7 (359 patients) trials for central neuraxial block and peripheral
      nerve block were included in the meta-analysis. Both central neuraxial block and
      peripheral nerve block were associated with increased induction time, reduced
      pain scores, and decreased need for postanesthesia care unit analgesics. However,
      central neuraxial block was not associated with decreased postanesthesia care
      unit bypass or time or reduced nausea despite reduced analgesics, and it was
      associated with a 35-min increase in total ambulatory surgery unit time. In
      contrast, peripheral nerve block was associated with decreased postanesthesia
      care unit need and decreased nausea but, again, not with decreased ambulatory
      surgery unit time. This meta-analysis indicates potential advantages for regional
      anesthesia, such as decreased postanesthesia care unit use, nausea, and
      postoperative pain. Although these factors have been proposed to reduce
      ambulatory surgery unit stay, neither central neuraxial block nor peripheral
      nerve block were associated with reduced ambulatory surgery unit time. Other
      factors, such as unsuitable discharge criteria and limitations of meta-analysis,
      may explain this discrepancy.

PMID- 16301235
TI  - Postdischarge symptoms after ambulatory surgery: first-week incidence, intensity,
      and risk factors.
AB  - Minor sequelae, such as pain, nausea, and drowsiness, often occur in surgical
      outpatients in the immediate postdischarge period. In this prospective,
      observational study was defined the daily incidence and intensity of several
      symptoms during the first week after surgery and determined predictive factors of
      minor morbidity. In two similar mixed ambulatory surgery units, 3910 patients
      received a questionnaire to grade daily the intensity of predefined symptoms on a
      4-point scale. Multinomial logistic regression was used to analyze risk factors,
      with adults and children as separate groups. Of these patients, 2754 (70%)
      responded. Patients experienced numerous minor sequelae during the first week
      after ambulatory surgery. Symptoms were common (up to 86% of all patients) on the
      initial days after surgery and were still reported by 24% of adults on the
      postoperative Day 7. In adults, pain was the most common symptom and, in
      comparison with other symptoms, was more often moderate or severe. Drowsiness was
      most common in children. Younger adults, older children, and women were more
      prone to experience minor morbidity. Longer duration of surgery led to increased
      likelihood of pain and nausea in all patients and increased the risk of several
      other symptoms in adults.

PMID- 16301236
TI  - The comparative effects of remifentanil or magnesium sulfate versus placebo on
      attenuating the hemodynamic responses after electroconvulsive therapy.
AB  - In this prospective, randomized, double-blind, placebo-controlled, crossover
      study we compared the effects of remifentanil or magnesium sulfate (MgSO4) versus
      placebo in attenuating the sympathetic response to electroconvulsive therapy.
      Twenty adults underwent a total of 115 anesthetics for therapeutic
      electroconvulsive therapy. Patients were randomly allocated twice into each of
      the three test groups: placebo control, MgSO4 30 mg/kg, or remifentanil 1.0
      microg/kg. Systolic and diastolic arterial blood pressures, heart rate, and
      oxygen saturations were recorded before IV access was established. Anesthesia was
      induced with thiopental 4 mg/kg. The trial drug was then administered and
      neuromuscular blockade was followed with succinylcholine 0.5 mg/kg before
      electroconvulsive therapy was performed. All measurements were repeated at 0, 1,
      3 and 10 min after the seizure ended. Remifentanil and MgSO4 produced a
      statistically significant attenuation of the increase in systolic arterial blood
      pressure at 0, 1, and 3 min (P < 0.05). Remifentanil, but not MgSO4 or placebo,
      attenuated the increase in heart rate at 1 and 3 min but not the peak rate.
      Remifentanil increased the duration of apnea (mean 90 s), with no other adverse
      respiratory effects. Mean seizure duration time was 33 (+/- 14) s, with no
      difference among the groups. In conclusion, remifentanil 1.0 microg/kg and MgSO4
      30 mg/kg attenuated the systolic arterial blood pressure response to
      electroconvulsive therapy without reducing the duration of seizure activity.
      Because MgSO4 has less effect on HR, it might offer advantages over remifentanil
      in patients at risk for post-electroconvulsive therapy bradycardia.

PMID- 16301237
TI  - An evaluation of general and spinal anesthesia techniques for prostate
      brachytherapy in a day surgery setting.
AB  - We evaluated four anesthetic techniques for transperineal brachytherapy of the
      prostate in a day-surgery setting: general anesthesia with either fentanyl and
      propofol total IV anesthesia (TIVA) or with fentanyl, thiopental, and isoflurane
      (F-P-I), versus spinal block using 5 mg of 0.5% large-dose spinal hyperbaric
      bupivacaine (LDS) or 2.5 mg of 0.5% hyperbaric bupivacaine plus fentanyl 25 mug
      small-dose spinal (SDS). Operating room time was shorter in the general
      anesthesia groups. TIVA patients voided earlier (103 +/- 41 min) than F-P-I
      patients (131 +/- 65 min), SDS (126 +/- 55 min), and LDS patients (169 +/- 65
      min; P < 0.05 TIVA versus all groups and between spinal groups). TIVA patients
      were discharged earlier (119 +/- 42 min) than F-P-I patients (160 +/- 69 min) and
      SDS or LDS patients (132 +/- 53 and 186 +/- 72 min, respectively; P < 0.05 versus
      all groups and between the spinal groups). There were no intergroup differences
      regarding postanesthesia nausea or vomiting, pain score, return to normal
      function at home, or overall satisfaction. Whereas all four techniques are
      suitable for this procedure, TIVA provides the earliest voiding and consequently
      fastest discharge. Between spinal techniques, the SDS technique requires more
      intraoperative sedation but provides earlier voiding and consequently earlier
      discharge. TIVA, general anesthesia with isoflurane and fentanyl, and two spinal
      techniques (5 mg of bupivacaine 0.5% or 2.5 mg of bupivacaine 0.5% plus 25 mug of
      fentanyl) are suitable techniques for transperineal brachytherapy in the day
      surgery setting. TIVA allows for earliest voiding and therefore fastest discharge
      home. Spinal block with 2.5 mg of bupivacaine plus 25 mug of fentanyl provides
      earlier voiding and consequently earlier discharge than 5 mg of bupivacaine
      alone.

PMID- 16301238
TI  - Inguinal herniorrhaphy under monitored anesthesia care with ilioinguinal
      iliohypogastric block: the impact of adding clonidine to ropivacaine.
AB  - There is no information concerning the association of ropivacaine and clonidine
      for ilioinguinal-iliohypogastric block. In this prospective, double-blind study,
      we randomly assigned 40 adult patients scheduled for inguinal herniorrhaphy under
      monitored anesthesia care to receive either 225 mg ropivacaine (7.5 mg/mL) alone
      (control group) or combined with 75 mug clonidine (clonidine group) for
      preoperative ilioinguinal-iliohypogastric block. After completion of surgery,
      patients were transferred to the postanesthesia care unit and were asked to stand
      up and walk around at the second postoperative hour. After leaving the
      postanesthesia care unit, patients could take oral propacetamol (500 mg) and
      codeine (30 mg) on request. Pain intensity was assessed with a 100 mm visual
      analog scale. Time to first request of supplemental analgesics (median [95%
      confidence interval]) was 10 h (7.1-14.5 h) and 9 h (6.4->24 h) respectively in
      the clonidine and control groups (P = 0.83). Pain at rest did not differ between
      groups whereas pain at motion was reduced on the third postoperative day in the
      clonidine group. More patients who received clonidine experienced orthostatic
      hypotension upon standing up within the first postoperative hours (6 of 20 versus
      1 of 20 in the control group; P < 0.05). In conclusion, the benefit of adding
      clonidine 75 mug to ropivacaine for ilioinguinal-iliohypogastric block for motion
      pain on the third postoperative day must be balanced with an increasing risk of
      orthostatic hypotension in the immediate postoperative period.

PMID- 16301239
TI  - Peripheral nerve block techniques for ambulatory surgery.
AB  - Peripheral nerve blocks (PNBs) have an increasingly important role in ambulatory
      anesthesia and have many characteristics of the ideal outpatient anesthetic:
      surgical anesthesia, prolonged postoperative analgesia, and facilitated
      discharge. Critically evaluating the potential benefits and supporting evidence
      is essential to appropriate technique selection. When PNBs are used for upper
      extremity procedures, there is consistent opioid sparing and fewer treatment
      related side effects when compared with general anesthesia. This has been
      demonstrated in the immediate perioperative period but has not been extensively
      investigated after discharge. Lower extremity PNBs are particularly useful for
      procedures resulting in greater tissue trauma when the benefits of dense
      analgesia appear to be magnified, as evidenced by less hospital readmission. The
      majority of current studies do not support the concept that a patient will have
      difficulty coping with pain when their block resolves at home. Initial
      investigations of outpatient continuous peripheral nerve blocks demonstrate
      analgesic potential beyond that obtained with single-injection blocks and offer
      promise for extending the duration of postoperative analgesia. The encouraging
      results of these studies will have to be balanced with the resources needed to
      safely manage catheters at home. Despite supportive data for ambulatory PNBs,
      most studies have been either case series or relatively small prospective trials,
      with a narrow focus on analgesia, opioids, and immediate side effects.
      Ultimately, having larger prospective data with a broader focus on outcome
      benefits would be more persuasive for anesthesiologists to perform procedures
      that are still viewed by many as technically challenging.

PMID- 16301240
TI  - Vasodilation from sufentanil in humans.
AB  - Sufentanil is a potent opioid that occasionally has been associated with
      hypotension. The mechanism behind this hypotension is unclear. We hypothesized
      that sufentanil had a direct effect on vascular smooth muscle to cause
      vasodilation. Sufentanil was infused into the brachial artery of 10 young,
      healthy volunteers at rates of 0.083, 0.167, 0.333, and 0.833 microg/min. Forearm
      blood flow was measured in both the experimental and control arms with venous
      occlusion plethysmography. The forearm blood flow in the infused arm increased in
      a dose-dependent fashion from 3.2 to 5.2 mL/min per 100 mL of tissue whereas
      simultaneous measurements in the control (non-infused) arm did not increase.
      Heart rate and mean arterial blood pressure were unchanged during the infusions.
      Furthermore, respiratory rate did not change at any infusion level and sedation
      did not occur. Thus, the data support that significant systemic "spillover" of
      sufentanil did not occur. We conclude that sufentanil has a direct, vasodilatory
      effect on human vascular tissue that is likely independent of a neurogenic or
      systemic mechanism.

PMID- 16301241
TI  - Peripheral N-methyl-D-aspartate receptors modulate nonadrenergic noncholinergic
      lower esophageal sphincter relaxation in rabbits.
AB  - We investigated the role of peripheral N-methyl-D-aspartate (NMDA) receptors in
      the myenteric plexus in mediating nonadrenergic noncholinergic (NANC) nitrergic
      relaxation of the lower esophageal sphincter (LES). Isometric contraction of LES
      strips from Japanese White rabbits was measured. NANC relaxation was induced by
      KCl (30 mM) in the presence of atropine and guanethidine. The concentration of
      3',5'-cyclic guanosine monophosphate (cGMP) was measured using a
      radioimmunoassay. The muscle strips were exposed to diethyldithiocarbamic acid
      (DETCA; 3 mM) to inactivate Cu/Zn superoxide dismutase. MK801 (5-methyl-10,11
      dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imine) inhibited NANC relaxation in a
      concentration-dependent manner (EC50 = 1.5 x 10(-5) M), accompanied by a decrease
      in cGMP production. NMDA induced a concentration-dependent relaxation, which was
      antagonized by MK801. NMDA stimulated cGMP production, which was inhibited by
      N(G)-nitro-L-arginine. Superoxide dismutase (100 U/mL) shifted the concentration
      response relationship of MK801-mediated inhibition of NANC relaxation to the
      right (EC50 = 3.4 x 10(-5) M), whereas catalase did not. Treatment with DETCA
      shifted the concentration-response relationships of pyrogallol-, ketamine- and
      MK801-mediated inhibition of NANC relaxation to the left. These findings suggest
      that the peripheral NMDA receptors mediate NANC smooth muscle relaxation, and
      modulate it, in part, through extracellular production of superoxide anions, thus
      eliminating the relaxant effect of endogenous nitric oxide.

PMID- 16301242
TI  - Identification of the central imidazoline receptor subtype involved in modulation
      of halothane-epinephrine arrhythmias in rats.
AB  - We previously reported that imidazoline receptors in the central nervous system
      are involved in modulation of halothane-epinephrine arrhythmias. These receptors
      have been subclassified as I1 and I2 subtypes, but it is not known which receptor
      subtype is involved in halothane-epinephrine-induced arrhythmias. We designed the
      present study to clarify the involvement of central imidazoline receptor subtype
      in the modulation of halothane-epinephrine-induced arrhythmias. Rats were
      anesthetized with halothane and monitored continuously for systemic arterial
      blood pressure and premature ventricular contractions. The arrhythmogenic dose of
      epinephrine was defined as the smallest dose that produces three or more
      premature ventricular contractions within a 15-s period. Intracisternal
      moxonidine dose-dependently inhibited the epinephrine-induced arrhythmias during
      halothane anesthesia. Intracisternal efaroxan, a selective I1 antagonist with
      little affinity for I2 subtype, but not rauwolscine, an alpha2 antagonist without
      affinity for imidazoline receptors, blocked the antiarrhythmic effect of
      moxonidine. Intracisternal BU 224 and 2-BFI, selective I2 ligands, also inhibited
      the epinephrine-induced arrhythmias dose-dependently; however, these effects were
      abolished by efaroxan. We conclude that central I1, but not I2, receptors play an
      important role in inhibition of halothane-epinephrine arrhythmia.

PMID- 16301243
TI  - Compartmental pharmacokinetics of dantrolene in adults: do malignant hyperthermia
      association dosing guidelines work?
AB  - Dantrolene is the only drug proven effective for prevention and treatment of
      malignant hyperthermia (MH). Current dosing recommendations are based on
      noncompartmental analyses and are largely empiric. They are also divergent, as
      evidenced by differing recommendations from the Malignant Hyperthermia
      Association of the United States (MHAUS) and European Sources. We determined the
      compartmental pharmacokinetics of dantrolene, simulated the concentration time
      course based on currently recommended dosing, and suggest an optimal regimen.
      Nine volunteers (55-89 kg) received IV infusions of dantrolene (5 mg/kg over 30
      min followed by 0.05 mg.kg(-1) . h(-1) for 5 h). Venous blood samples were drawn
      for up to 60 h, and dantrolene plasma concentrations were determined by reverse
      phase, high-performance liquid chromatography. One, two, and three compartmental
      models were fitted to the data, and a covariate analysis was performed. All
      calculations were performed with NONMEM using the population approach. The data
      were adequately described by a two-compartment model with the following typical
      variable values (median +/- se): volumes of distribution V1= 3.24 +/- 0.61 L; V2=
      22.9 +/- 1.53 L; plasma clearance CL el= 0.03 +/- 0.003 L/min; and distributional
      clearance CL dist= 1.24 +/- 0.22 L/min. All parameters were scaled linearly with
      weight. Simulations of European recommendations for treatment of MH lead to
      plasma concentrations converging to 14-18 mg/L within 24 h. Simulating MHAUS
      guidelines (intermittent bolus administration) yielded peak and trough plasma
      concentrations ranging from 6.7-22.6 mg/L. Based on our findings, we propose an
      infusion regimen adjusted to the initial bolus dose(s) required to control
      symptoms. This strategy maintains the individualized therapeutic concentrations
      and improves stability of plasma concentrations.

PMID- 16301244
TI  - Neuroendocrine stress response and heart rate variability: a comparison of total
      intravenous versus balanced anesthesia.
AB  - Attenuating intraoperative stress is a key factor in improving outcome. We
      compared neuroendocrine changes and heart rate variability (HRV) during balanced
      anesthesia (BAL) versus total IV anesthesia (TIVA). Forty-three patients randomly
      received either BAL (sevoflurane/remifentanil) or TIVA (propofol/remifentanil).
      Depth of anesthesia was monitored by bispectral index. Stress hormones were
      measured at 7 time points (P1 = baseline; P2 = tracheal intubation; P3 = skin
      incision; P4 = maximum operative trauma; P5 = end of surgery; P6 = tracheal
      extubation; P7 = 15 min after tracheal extubation). HRV was analyzed by power
      spectrum analysis: very low frequency (VLF), low frequency (LF), high frequency
      (HF), LF/HF ratio, and total power (TP). LF/HF was higher in TIVA at P6 and TP
      was higher in TIVA at P3-7 (P3: 412.6 versus 94.2; P4: 266.7 versus 114.6; P5:
      290.3 versus 111.9; P6: 1523.7 versus 658.1; P7: 1225.6 versus 342.6 ms2)). BAL
      showed higher levels of epinephrine (P7: 100.5 versus 54 pg/mL), norepinephrine
      (P3: 221 versus 119.5; P4: 194 versus 130.5 pg/mL), adrenocorticotropic hormone
      (P2 10.5 versus 7.7; P5: 5.3 versus 3.6; P6: 10.9 versus 5.3; P7: 20.5 versus 7.1
      pg/mL) and cortisol (P7: 6.9 versus 3.9 microg/dL). This indicates a higher
      sympathetic outflow using BAL versus TIVA during ear-nose-throat surgery.

PMID- 16301245
TI  - The dosing-time dependent effects of intravenous hypnotics in mice.
AB  - Chronobiology, which focuses on the biological rhythms that occur in the
      organization of living organisms, has been studied for several decades.
      Chronopharmacology, however, has received little attention until recently. We
      examined the hypnotic duration of intraperitoneally administered ketamine,
      pentobarbital, propofol, midazolam, and ethanol, to test whether they have
      obvious dosing-time dependent effects. Male C57BL/6 mice, which showed clear
      circadian rhythms of water-intake under a strict 12-h lighting cycle, were used.
      All tested drugs had significantly longer episodes of loss of righting reflex
      when administered at 22:00 (early active phase) than at 10:00 (early inactive
      phase). This dosing-time dependent hypnotic duration did not depend on the
      contents and activities of cytochrome P450 enzymes in the liver. These findings
      might be of clinical benefit in deciding the administration time and doses of
      anesthetics.

PMID- 16301246
TI  - Hetastarch allergy and positive latex radioallergosorbent test in a patient
      suffering cardiovascular decompensation during multiple perioperative periods.
AB  - The cause of sudden cardiovascular collapse in the perioperative period can be
      elusive. Allergy may be overlooked as a cause. When allergy is considered, latex
      is often suspected. Because hetastarch is frequently used in situations involving
      hypovolemia and hypotension, and because allergic reactions to it are rare, it
      may be overlooked as a possible allergen. We report a case of a patient suffering
      cardiovascular decompensation during four nonconsecutive perioperative periods
      before it was determined that she was allergic to hetastarch. She also had a very
      highly positive latex radioallergosorbent test, suggesting a latex allergy.

PMID- 16301247
TI  - The influence of a muscle relaxant bolus on bispectral and datex-ohmeda entropy
      values during propofol-remifentanil induced loss of consciousness.
AB  - Studies investigating the influence of muscle relaxants on the bispectral index
      have yielded contradictory results. In our prospective, randomized, double-blind
      experiments, patients received a fixed target concentration of remifentanil along
      with a target-controlled infusion of propofol, titrated until loss of
      consciousness. Two minutes after loss of consciousness, the study group received
      a bolus injection of atracurium, whereas the control group received a placebo.
      The following variables were recorded: bispectral index, spectral edge frequency,
      electromyographic activity, state entropy, and response entropy provided by the
      Datex-Ohmeda Entropy monitor. Similar values were obtained in both groups at loss
      of consciousness. Placebo administration induced a decrease in bispectral index
      (P < 0.002), spectral edge frequency (P < 0.05), electromyographic activity (P <
      0.02), state entropy (P < 0.05), and response entropy (P < 0.01) compared with
      the values measured at loss of consciousness. Atracurium administration induced a
      decrease in bispectral index (P < 0.0001), spectral edge frequency (P < 0.01),
      electromyographic activity (P < 0.0001), state entropy (P < 0.0001), and response
      entropy (P < 0.0001) values. Decreases in bispectral index (P < 0.05),
      electromyographic activity (P < 0.0001), and response entropy (P < 0.01) were
      larger after atracurium than placebo injection. In lightly anesthetized patients,
      myorelaxant administration decreases bispectral index and response entropy, but
      not state entropy values.

PMID- 16301248
TI  - An evaluation of a vibro-tactile display prototype for physiological monitoring.
AB  - Visual displays and auditory alarms are used to convey information on
      physiological variables in an operating room. However, the exponential growth in
      the number of physiological variables and the high probability of false alarms
      has amplified demands on the clinician's attention. We have extended existing
      tactile technology to improve situational awareness and produce a practical
      clinical advisory device. A vibro-tactile display, using two vibrating motors
      applied to the volar surface of the forearm, was compared to an auditory alarm in
      a simulated clinical environment. Compared with auditory alarms, the vibro
      tactile alarm was as easy to learn and had a better identification rate when used
      alone or combined with the auditory alarm. Most users preferred the vibro-tactile
      alarm although the prototype caused some discomfort. Furthermore, a combined
      vibro-tactile and auditory alarm had reduced accuracy when compared with the
      vibro-tactile alarm alone. The vibro-tactile modality shows considerable promise
      for clinical practice but will require further clinical testing and refinement,
      especially with regard to user comfort.

PMID- 16301249
TI  - Radiation exposure to anesthesia personnel: the impact of an electrophysiology
      laboratory.
AB  - Anesthesia care providers are vulnerable to radiation exposure during a number of
      diagnostic and therapeutic procedures. In this study I examined the radiation
      exposure to members of a small department of anesthesiology. The aggregate
      radiation exposure to all members of the department doubled subsequent to the
      introduction of an electrophysiology laboratory.

PMID- 16301250
TI  - Tolerance to opioid analgesia: why do we differ from rats?

PMID- 16301251
TI  - Spinal L-type calcium channel blockade abolishes opioid-induced sensory
      hypersensitivity and antinociceptive tolerance.
AB  - Recent studies have suggested that prolonged exposure to morphine results in the
      development of paradoxical, abnormal enhanced pain. It has also been suggested
      that this enhanced pain state may be interpreted as antinociceptive tolerance.
      Although the precise mechanisms that drive opioid-induced abnormal pain are not
      well known, considerable evidence suggests that this state may be supported by
      enhanced, stimulus-evoked excitatory transmission. We hypothesized that blockade
      of L-type calcium channels, which are critical for excitatory neurotransmitter
      release, would alter the development of opioid-induced hyperalgesia and
      antinociceptive tolerance. Male, Swiss-Webster mice received twice-daily
      intrathecal injections of morphine (10 microg) alone or in combination with
      amlodipine (10 microg) for 8 days. Mice receiving repeated morphine injections
      developed enhanced responses to tactile and thermal stimuli. These
      hypersensitivities were prevented by the coadministration of the putative
      selective L-type calcium channel blocker amlodipine. Moreover, mice receiving
      morphine for 8 days demonstrated a significant rightward shift of the morphine
      antinociceptive dose-response curve, indicative of antinociceptive tolerance,
      whereas those that also received amlodipine along with morphine did not
      demonstrate tolerance. These results suggest that blockade of the L-type calcium
      channels with amlodipine prevented opioid-induced hyperalgesia and the expression
      of antinociceptive tolerance to spinal morphine, presumably by reducing stimulus
      induced excitatory neurotransmitter release.

PMID- 16301252
TI  - Local anesthetics for the treatment of neuropathic pain: on the limits of meta
      analysis.

PMID- 16301253
TI  - Systemic administration of local anesthetics to relieve neuropathic pain: a
      systematic review and meta-analysis.
AB  - We reviewed randomized controlled trials to determine the efficacy and safety of
      systemically administered local anesthetics compared with placebo or active
      drugs. Of 41 retrieved studies, 27 trials of diverse quality were included in the
      systematic review. Ten lidocaine and nine mexiletine trials had data suitable for
      meta-analysis (n = 706 patients total). Lidocaine (most commonly 5 mg/kg IV over
      30-60 min) and mexiletine (median dose, 600 mg daily) were superior to placebo
      (weighted mean difference on a 0-100 mm pain intensity visual analog scale = 
      10.60; 95% confidence interval: -14.52 to -6.68; P < 0.00001) and equal to
      morphine, gabapentin, amitriptyline, and amantadine (weighted mean difference = 
      0.60; 95% confidence interval: -6.96 to 5.75) for neuropathic pain. The
      therapeutic benefit was more consistent for peripheral pain (trauma, diabetes)
      and central pain. The most common adverse effects of lidocaine and mexiletine
      were drowsiness, fatigue, nausea, and dizziness. The adverse event rate for
      systemically administered local anesthetics was more than for placebo but
      equivalent to morphine, amitriptyline, or gabapentin (odds ratio: 1.23; 95%
      confidence interval: 0.22 to 6.90). Lidocaine and mexiletine produced no major
      adverse events in controlled clinical trials, were superior to placebo to relieve
      neuropathic pain, and were as effective as other analgesics used for this
      condition.

PMID- 16301254
TI  - A single dose of intrathecal morphine in rats induces long-lasting hyperalgesia:
      the protective effect of prior administration of ketamine.
AB  - An active pronociceptive process involving N-methyl-D-aspartate (NMDA) receptor
      activation is initiated by opioid administration, leading to opioid-induced pain
      sensitivity. Experimental observations in rats have reported reduction of
      baseline nociceptive threshold after prolonged spinal opioid administration. In
      this study we sought to determine whether a single dose of intrathecal morphine
      can induce hyperalgesia in uninjured rats and to assess the effects of
      pretreatment with the NMDA-antagonist ketamine on nociceptive thresholds.
      Sensitivity to nociceptive stimuli (paw pressure test) was assessed for several
      days after an acute intrathecal injection of morphine (5 microg and 10 microg) in
      male Sprague-Dawley rats. The effects of subcutaneously administered NMDA
      receptor antagonist ketamine (10 mg/kg) before intrathecally administered
      morphine were also evaluated. A single intrathecal injection of morphine led to a
      biphasic effect on nociception; early analgesia associated with an increase in
      the nociceptive threshold lasting 3-5 h was followed by delayed hyperalgesia
      associated with a decrease in the nociceptive threshold lasting 1-2 days.
      Subcutaneous ketamine did not significantly modify the early analgesic component
      but almost completely prevented the delayed decrease in nociceptive threshold
      after intrathecal administration of morphine. A single intrathecal injection of
      morphine in rats produces a delayed and sustained hyperalgesia linked to the
      development of opioid-induced pain sensitivity.

PMID- 16301255
TI  - A role for endothelin in neuropathic pain after chronic constriction injury of
      the sciatic nerve.
AB  - The purpose of this study was to explore the role of endothelin in neuropathic
      pain. Endothelins (ET) are a family (ET-1, ET-2, ET-3) of ubiquitously expressed
      peptides involved in control of vascular tone. Injected ET-1 causes intense pain
      via activation of ETA receptors, modulated by analgesic signals initiated by ETB
      receptor activation. Using a rat model of chronic constriction injury of the
      sciatic nerve, we found that pharmacologic ETA receptor antagonism acutely and
      significantly reduced thermal and mechanical hyperalgesic responses 5 days after
      injury. Furthermore, ET-1 and the ETA receptor are locally upregulated at the
      site of chronic constriction injury at both the message and the protein levels,
      suggesting that ET-1 may be involved in establishing pain after the injury. These
      data point to ET-1 as an important mediator of pain in general and suggest that
      ETA antagonism deserves study as a potential novel therapy for neuropathic pain.

PMID- 16301256
TI  - The effects of diacerhein on mechanical allodynia in inflammatory and neuropathic
      models of nociception in mice.
AB  - In this study we analyzed the systemic antiallodynic properties of diacerhein, a
      drug used to treat osteoarthritis, in inflammatory and neuropathic models of
      nociception in mice. The effects of diacerhein were compared with those of
      gabapentin, a drug used clinically for the management of neuropathic pain.
      Similar to gabapentin, diacerhein was able to significantly reverse the
      mechanical allodynia induced by carrageenan. A significant inhibition of
      carrageenan-induced nociception was also observed when diacerhein was
      administered by the intrathecal but not by the intraplantar route. The treatment
      with diacerhein or with gabapentin also inhibited the mechanical allodynia
      induced by complete Freund's adjuvant (CFA) or after the partial ligation of the
      sciatic nerve (PLSN). In the same range of doses, diacerhein or gabapentin did
      not affect the locomotor activity, motor coordination, or body temperature of the
      animals. The present results indicate that diacerhein produces marked
      antiallodynic effects in carrageenan and CFA nociception models and also inhibits
      the neuropathic pain after PLSN, with an efficacy similar to that observed for
      gabapentin. Diacerhein may be a potentially interesting tool for the management
      of inflammatory and neuropathic pain.

PMID- 16301257
TI  - Measuring the size of the extracellular fluid space using bromide, iohexol, and
      sodium dilution.
AB  - There is a need to find methods to assess the size of the extracellular fluid
      (ECF) volume without involving radioactive tracers. For this purpose, we applied
      3 methods for measuring the ECF volume in 10 male volunteers (mean age, 34 yr).
      Steady-state plasma bromide concentration (control) was compared to the results
      of kinetic analysis of plasma iohexol and to kinetic analysis of the dilution of
      serum sodium after IV infusion of 1 L of isotonic mannitol. The volume of
      distribution of these tracers was used to indicate the ECF volume. The results
      disclosed statistically significant correlations between the results of all 3
      methods, although the average sodium dilution showed 0.7 L lower values than
      iohexol and 1.4 L lower than bromide. All three methods correlated significantly
      with body weight. The percentage of the body weight indicated by the methods was
      18.3% (3.1%) for sodium, 19.6% (1.0%) for iohexol, and 20.5% (1.1%) for bromide.
      We conclude that sodium dilution may be performed at bedside but iohexol and
      bromide showed less intersubject variability. Iohexol simultaneously measures the
      glomerular filtration rate and should be a viable clinical option if the hospital
      performs routine assessments of kidney function using this tracer.

PMID- 16301258
TI  - Central venous catheter colonization in critically ill patients: a prospective,
      randomized, controlled study comparing standard with two antiseptic-impregnated
      catheters.
AB  - In this prospective, randomized, controlled, unblinded study, we compared
      colonization rates of a standard, unimpregnated central venous catheter (CVC)
      with rates for silver-coated and chlorhexidine-silversulfadiazine (CH-SS)
      impregnated CVC. Patient characteristics, CVC insertion site, indwelling time,
      and colonization detected by semiquantitative and quantitative microbiologic
      techniques were documented. Two-hundred-seventy-five critically ill patients were
      included into the study protocol. One-hundred-sixty standard, 160 silver (S)
      coated, and 165 externally impregnated CH-SS CVC were inserted. There was a
      significant difference in CVC colonization rates among study groups (P = 0.029).
      There was no difference in the colonization rate and the colonization per 1000
      catheter days between standard and S-coated (P = 0.564; P = 0.24) or CH-SS-coated
      CVC (P= 0.795; P = 0.639). When comparing antiseptic CVC with each other,
      colonization rates were significantly less with CH-SS-impregnated than with S
      coated CVC (16.9% versus 7.3%; P = 0.01; 18.2 versus 7.5 of 1000 catheter days; P
      = 0.003; relative risk, 0.43; 95% confidence interval, 0.21-0.85). Whereas
      standard and S-coated CVC were first colonized 2 and 3 days after insertion,
      respectively, CH-SS CVC were first colonized only after 7 days. In conclusion,
      antiseptic-impregnated CVC could not prevent catheter colonization when compared
      with standard polyurethane catheters in a critical care setting with infrequent
      catheter colonization rates and CVC left in place for >10 days.

PMID- 16301259
TI  - Early colloid replacement therapy in a near-fatal model of hemorrhagic shock.
AB  - Several controlled, experimental, hypotensive models of hemorrhagic shock have
      evaluated the effects of timing, rate, and types of fluid replacement. In a near
      fatal experimental model we evaluated the hemodynamic and metabolic effects of
      two types of solutions for fluid resuscitation. In this study, 30 young Large
      White pigs were randomly assigned to three groups: Group I (control, n= 10), not
      bled; Group II (hydroxyethyl starch, HES, n = 10), submitted to controlled
      hemorrhage to a mean arterial blood pressure (MAP) of 30 mmHg and blood lactate
      >10 mM/L, at which time resuscitation was initiated with 7 mL/kg of HES 130/0.4
      6% followed by 33 mL/kg of lactated Ringer's solution (LR) and retransfusion;
      Group III (LR, n = 10), submitted to controlled hemorrhage to a MAP of 30 mmHg
      and blood lactate >10 mM/L, at which time resuscitation was initiated with 40
      mL/kg of LR followed by retransfusion. The resuscitation with HES 130/0.4 proved
      to be superior to LR, expressed by hemodynamic and perfusion variables. Despite
      improvement in tissue perfusion, MAP did not totally return to baseline values.
      In conclusion, early colloid infusion resulted in prompt recovery of tissue
      perfusion when compared with infusion with an equal volume of crystalloid.

PMID- 16301260
TI  - A single adrenocorticotropic hormone stimulation test does not reveal adrenal
      insufficiency in septic shock.
AB  - The diagnosis of adrenocortical insufficiency in critically ill patients is
      complex. The adrenocorticotropic hormone (ACTH) stimulation test is a widely
      accepted method for assessing the adequacy of adrenal function in intensive care
      units, but it is possible that there may be wide variations in responses to the
      test over a short period of time. In this prospective study, we investigated the
      reproducibility of the ACTH stimulation test in 20 patients with sepsis, in 20
      patients with septic shock, and in 20 critically ill patients without sepsis. Two
      consecutive ACTH stimulation tests were performed within 24 h after intensive
      care unit admission or at the onset of sepsis. In patients without sepsis there
      was good correlation between ACTH responses on days 1 and 2 (Pearson's
      correlation coefficient, 0.689; P = 0.001). In contrast, in patients with septic
      shock no correlation was observed between the two ACTH responses (Pearson's
      correlation coefficient, 0.401; P = 0.080). We conclude that the results of the
      ACTH stimulation tests are poorly reproducible in septic shock and a single ACTH
      stimulation test may not be the best method to diagnose adrenal insufficiency in
      these patients.

PMID- 16301261
TI  - Inhibition of poly (ADP-ribose) synthetase improves pulmonary arterial
      endothelium-dependent relaxation after ischemic-reperfusion injury of splanchnic
      artery in rats.
AB  - The role of poly (adenosine diphosphate-ribose) synthetase (PARS) in the
      contractile and relaxant responses of pulmonary arteries injured by ischemia and
      reperfusion (IR) of splanchnic artery has not been evaluated. We examined these
      responses by using 3-aminobenzamide, a pharmacological inhibitor of PARS. IR
      models in rats were induced by clamping the superior mesenteric artery for 60
      min, followed by release of the clamp for 60 min. In the 2 treated groups, 5 or
      10 mg/kg of 3-aminobenzamide was administered as an IV bolus at 10 min before
      reperfusion, followed by infusion rates of 5 and 10 mg.kg(-1).h(-1),
      respectively, during the period of reperfusion (IR + PARS inhibitor 5 and 10
      groups). In the vehicle-treated group, 3-aminobenzamide was not given, but IV
      saline was administered (IR group). In the control group, surgery was performed,
      but the superior mesenteric artery was not occluded (sham group). The pulmonary
      arteries were isolated, and effects of drugs were evaluated in vitro. The IR
      group showed no attenuation of the contractile responses of the pulmonary artery
      to phenylephrine. The relaxant responses to endothelium-dependent vasodilators,
      acetylcholine, and A23187 in the IR group were significantly inhibited when
      compared with the sham group. The reduction in the relaxant response to
      endothelium-dependent vasodilators was improved in the IR + PARS inhibitor 5 and
      10 groups when compared with the IR group. We concluded that IR attenuated the
      relaxant responses of the pulmonary artery to endothelium-dependent vasodilators
      and that PARS inhibitors ameliorate the reduction in the relaxant response.

PMID- 16301262
TI  - Drotrecogin alfa (activated) does not affect intracellular production of
      interleukin-6 and tumor necrosis factor-alpha in endotoxin-stimulated human
      monocytes.
AB  - In this ex vivo laboratory study, we investigated the effects of drotrecogin alfa
      (activated) (DA(a)), a recombinant form of human activated protein C, on the
      intracellular expression of interleukin (IL)-6 and tumor necrosis factor (TNF)
      alpha on lipopolysaccharide (LPS)-stimulated human monocytes in a whole blood
      system. Whole blood samples from 10 healthy volunteers were stimulated with LPS
      (0.2 ng/mL) and incubated with 0.01, 0.1, 1, 10, and 100 nM of (final
      concentration) DA(a) for 3 h at 37 degrees C and 5% CO2. Intracellular expression
      of IL-6 and TNF-alpha was assessed by flow cytometry. Our investigation showed
      that DA(a), at any of the concentrations tested, did not affect intracellular IL
      6 and TNF-alpha production in LPS-stimulated human monocytes after 3 h of
      incubation. The results of this investigation led us to conclude that any
      antiinflammatory activity of DA(a), if present, does not occur via detectible
      decreases in the production of proinflammatory cytokines IL-6 and TNF-alpha in
      human monocytes.

PMID- 16301263
TI  - The use of small-dose theophylline for the treatment of bradycardia in patients
      with spinal cord injury.
AB  - Small-dose theophylline can be a useful alternative in the treatment of
      bradycardia in patients with spinal cord injury. In this series of three cases, I
      describe its successful use for this indication. In one case, initiation of
      theophylline treatment also increased respiratory drive and minute ventilation. A
      possible mechanism is that theophylline increases the force of contraction of
      diaphragmatic muscles because of enhancement of calcium uptake through an
      adenosine-mediated channel. The antibradycardiac effect is probably mediated
      through one or more different molecular mechanisms, which seem to be mediated by
      inhibition of phosphodiesterase 3.

PMID- 16301264
TI  - Airway problems caused by hypogonadism in male patients undergoing neurosurgery.
AB  - Unanticipated difficult endotracheal intubations can pose challenges for the
      anesthesiologist. Risks include airway injury, hypoxemia, and death. There is
      intubation difficulty in various conditions including Downs syndrome,
      achondroplasia, acromegaly, and dwarfism. We describe difficulty in intubating
      the trachea with an appropriate sized endotracheal tube in two young male
      patients with hypogonadism presenting for neurosurgical procedures under general
      anesthesia. We discuss the role of hypogonadism and the effects of gonadotropin
      hormones on pubertal laryngeal growth in male patients.

PMID- 16301265
TI  - Circulating mature adrenomedullin is related to blood volume in full-term
      pregnancy.
AB  - Plasma adrenomedullin concentration increases during pregnancy. We measured blood
      volume and mature adrenomedullin concentration in plasma and cerebrospinal fluid
      and examined whether mature adrenomedullin in plasma and cerebrospinal fluid was
      associated with increasing blood volume during pregnancy. We enrolled 47 women
      undergoing surgery with spinal anesthesia in this study. We first measured mature
      adrenomedullin concentration in plasma and cerebrospinal fluid of nonpregnant
      women undergoing orthopedic surgery, pregnant women between 15 and 18 wk of
      gestation undergoing gynecological surgery, and pregnant women at full-term
      undergoing cesarean delivery. The second study included 20 healthy and full-term
      parturients scheduled for cesarean delivery. We measured arterial blood pressure
      and blood volume by noninvasive pulse spectrophotometry using indocyanine green.
      Plasma-mature adrenomedullin concentration was 1.24 +/- 0.98, 2.79 +/- 1.23, 4.79
      +/- 2.61 fmol/mL (mean +/- sd) in the nonpregnant, the early gestation, and the
      full-term groups, respectively. But in cerebrospinal fluid, mature adrenomedullin
      did not significantly increase. Furthermore, mature adrenomedullin in plasma, but
      not cerebrospinal fluid, had a significant correlation with blood volume per unit
      body weight (r2= 0.46; P = 0.0009). These findings demonstrate that plasma-mature
      adrenomedullin concentration increased and that increased plasma-mature
      adrenomedullin is associated with increased blood volume during pregnancy.

PMID- 16301266
TI  - The use of central neuraxial techniques in parturients with factor V leiden
      mutation.
AB  - The factor V Leiden (FVL) mutation is a leading cause of thrombosis, particularly
      during pregnancy. During pregnancy, women with thrombotic disorders including FVL
      are often considered candidates for antepartum anticoagulation with low molecular
      weight heparin. Pregnancy complications related to thrombosis and the
      unpredictable timing of labor cause unique challenges with regard to the
      provision of regional anesthesia. A patient with heterozygotic FVL presenting
      with thrombotic disease and a complicated anticoagulation status lead us to
      review 16 additional parturients with FVL. This report focuses on the anesthetic
      implications that arise in parturients with FVL. We recommend that
      anesthesiologists be made aware of FVL patients before their due date,
      anticoagulation with low molecular weight heparin should be transitioned to
      unfractionated heparin before the 38th gestational week, and multidisciplinary
      collaborative investigation and care should continue for this disorder.

PMID- 16301267
TI  - Continuous femoral nerve blockade or epidural analgesia after total knee
      replacement: a prospective randomized controlled trial.
AB  - Because postoperative pain after total knee replacement (TKR) can be severe, we
      compared the analgesic efficacy of continuous femoral nerve blockade (CFNB) and
      continuous epidural analgesia (CEA) after TKR in this prospective randomized
      trial. Patients undergoing TKR under spinal anesthesia were randomized to receive
      either a femoral infusion of bupivacaine 0.2% (median infusion rate 9.3 mL/h) (n
      = 53) or an epidural infusion of ropivacaine 0.2% with fentanyl 4 microg/mL
      (median infusion rate 7.6 mL/h) (n = 55). Adjuvant analgesics were oral rofecoxib
      and oxycodone and IV morphine. Pain, nausea and vomiting, hypotensive episodes,
      motor block, range of knee movement, and rehabilitation milestones were assessed
      postoperatively. There were equivalent pain scores, range of movement, and
      rehabilitation in both groups. There was significantly less nausea and vomiting
      in the CFNB group (P < 0.002). The CFNB group received more rofecoxib (P < 0.04)
      and oxycodone (P < 0.005) than the CEA group. The operative limb displayed more
      motor block than the nonoperative limb in both groups at the level of the hip and
      knee for up to 48 h (P < 0.05, Mann-Whitney U-test), but there was no difference
      between groups in the nonoperative limb. CFNB is an effective regional component
      of a multimodal analgesic strategy after TKR.

PMID- 16301268
TI  - A prospective comparative study of two indirect methods for confirming the
      localization of an epidural catheter for postoperative analgesia.
AB  - We prospectively evaluated, in randomized order, 2 indirect methods of confirming
      the localization of an epidural catheter for postoperative analgesia in 218
      surgical patients: epidural stimulation test (EST) and epidural pressure waveform
      analysis (EPWA). The epidural space was localized by using a loss of resistance
      technique. All catheters were inserted 5 cm into the epidural space and primed
      with 5 mL of 0.9% normal saline. There were no differences between the methods:
      the positive predictive value and specificity were high (100% in both groups),
      but the sensitivity was moderate (80% for EST and 81% for EPWA) and the negative
      predictive value was low (16% for EST and 17% for EPWA). Combining both methods
      yielded better sensitivity (97%) and negative predictive value (57%) (P < 0.001).
      The sensitivity of EST was increased to 87% (P < 0.05) if sensory response was
      included as well as motor response for stimulation less than 10 mA. We suggest
      the inclusion of sensory response in the appropriate dermatome at a current <10
      mA as a criterion for adequate epidural catheter localization for EST testing.
      EPWA sensitivity was significantly better with older patients: 94% for patients
      older than 80 yr compared with 63% for patients younger than 40, 73% for patients
      40 to 60, and 85% for patients aged 60 to 80 yr (P = 0.03). We conclude that the
      two tests are comparable for confirming catheter placement.

PMID- 16301269
TI  - Epidural fentanyl speeds the onset of sensory and motor blocks during epidural
      ropivacaine anesthesia.
AB  - In this study we examined the onset times of sensory and motor block during
      epidural ropivacaine anesthesia with and without the addition of fentanyl to the
      epidural solution. Forty-five young male patients undergoing knee arthroscopic
      surgery were randomly allocated into 3 groups of 15 patients each: epidural
      fentanyl (EF; epidural administration of 15 mL of 1% ropivacaine plus 100 mug
      fentanyl followed by IV injection of 2 mL of normal saline); IV fentanyl (IF;
      epidural administration of 15 mL of 1% ropivacaine plus 2 mL of normal saline
      followed by IV injection of 100 mug fentanyl); and control (C; epidural
      administration of 15 mL of 1% ropivacaine plus 2 mL of normal saline followed by
      IV injection of 2 mL of normal saline). The sensory and motor blocks were
      assessed by pinprick and modified Bromage scale, respectively. The hemodynamic
      changes, postepidural shivering, and side effects of epidural fentanyl were also
      recorded. There was no difference in the distribution of age, weight, and height
      among the 3 groups. The onset time of sensory block to the T10 dermatome was
      significantly more rapid in the EF group (13.0 +/- 3.0 min) than in the IF group
      (16.2 +/- 3.5 min, P < 0.05) or C group (17.7 +/- 3.6 min, P < 0.05). The onset
      times of motor block up to Bromage scale 1 and 2 were significantly more rapid in
      the EF group (11.9 +/- 4.6 and 24.4 +/- 5.9 min) than in the IF group (16.9 +/-
      4.7 and 30.8 +/- 5.6 min, P < 0.05) or C group (18.3 +/- 4.9 and 32.7 +/- 5.7
      min, P < 0.05). There was no difference in the incidence of shivering among the
      three groups. Pruritus was observed in three patients of the EF group and one
      patient of the IF group. No nausea, vomiting, respiratory depression, urinary
      retention, or hypotension was observed in any patient. We conclude that epidural
      administration of the mixture of 100 mug fentanyl and 1% ropivacaine solution
      accelerated the onset of sensory and motor blocks during epidural ropivacaine
      anesthesia without significant fentanyl-related side effects.

PMID- 16301270
TI  - Tissue injury from tricyclic antidepressants used as local anesthetics.
AB  - Neurotoxicity has been reported with tricyclic antidepressants (TCAs) used as
      local anesthetics. We examined the hypothesis that TCAs cause tissue injury,
      particularly myotoxicity, as occurs with many local anesthetics. Animals were
      given sciatic nerve injections with 0-80 mM doxepin, amitriptyline, or
      bupivacaine (1.5 mL for histological studies, 0.3 mL for neurobehavioral
      studies). Four days after injection, the TCAs caused ischemic tissue injury.
      Subcutaneous tissue showed expansion and hardening, with hemorrhage and adhesion
      to overlying skin. Muscle was diffusely pale. Histopathology showed coagulative
      necrosis of muscle and surrounding soft tissues, with thrombus formation in
      vasculature near affected areas. These findings were much reduced with
      bupivacaine. TCA-injected and bupivacaine-injected animals also developed
      characteristic local anesthetic myotoxicity. Amitriptyline proved less potent
      than bupivacaine as a local anesthetic: the concentrations required to provide
      100 min of nerve block were 20 mM and 3 mM, respectively. Some animals receiving
      large concentrations of amitriptyline developed spontaneous recrudescence of
      nerve blockade or had irreversible nerve blockade, both of which may reflect
      nerve injury. Neither finding occurred in animals injected with bupivacaine. TCAs
      do not appear to offer any advantages over conventional local anesthetics and do
      appear to risk substantially increased toxicity.

PMID- 16301271
TI  - Signs of inflammation after sciatic nerve block in pigs.
AB  - Nerve stimulators are widely used to assist with peripheral nerve blocks but do
      not eliminate the risk of nerve injury. We evaluated the histologic findings 6 h
      after sciatic nerve block with bupivacaine in pigs. When a motor response was
      still obtained with a current <0.2 mA (n = 10), the postmortem microscopic
      evaluation revealed lymphocytes and granulocytes sub-, peri-, and intraneurally
      in 5 (50%) of 10 pigs. No signs of inflammation were observed when the muscle
      contraction was achieved with a current between 0.3 and 0.5 mA (P = 0.03). In
      conclusion, the current required to elicit a motor response, the position of the
      needle tip, and the subsequent likelihood of nerve damage merit further
      evaluation.

PMID- 16301272
TI  - Persistent cauda equina syndrome with no identifiable facilitating condition
      after an uneventful single spinal administration of 0.5% hyperbaric bupivacaine.
AB  - We diagnosed cauda equina syndrome 15 h after uneventful single spinal
      administration of 0.5% hyperbaric bupivacaine 12.5 mg through a 27-gauge pencil
      point type needle. No preexisting neurologic disorder was recorded. There was no
      pain or paresthesia during needle placement or drug injection. The sensory levels
      were bilateral, symmetric, and caudal to T8. Resolution of most of the symptoms
      occurred within a few days but some foot drop persisted for 2 yr after the
      procedure. Bupivacaine neurotoxicity is suggested by the absence of any other
      identifiable cause for this neurologic deficit.

PMID- 16301274
TI  - Detection, evaluation, and management of anemia in the elective surgical patient.
AB  - The prevalence of anemia in elective surgical patients may be as frequent as 75%
      in certain populations. A national audit demonstrated that 35% of patients
      scheduled for joint replacement therapy have a hemoglobin <13 g/dL on
      preadmission testing. Standard practice currently consists of preadmission
      testing 3 to 7 days before an elective operative procedure, precluding the
      opportunity to effectively evaluate and manage a patient with unexpected anemia.
      Therefore, a standardized approach for the detection, evaluation, and management
      of anemia in the preoperative surgical setting was identified as an unmet medical
      need. To address this knowledge gap, we convened a panel of physicians to develop
      a clinical care pathway for anemia management in this setting. Elective surgery
      patients should receive a hemoglobin (Hgb) determination a minimum of 30 days
      before the scheduled surgical procedure. Because the identification and
      evaluation of anemia in this setting will assist in expedited diagnosis and
      treatment of underlying comorbidities and will improve patient outcomes,
      unexplained anemia (Hgb <12 g/dL for females and <13 g/dL for males) should cause
      elective surgery to be deferred until an evaluation can be performed.

PMID- 16301273
TI  - Independent risk factors for postoperative shivering.
AB  - Postoperative shivering (PAS) is uncomfortable for patients and potentially
      risky. In this observational trial we sought to identify independent risk factors
      for PAS after general anesthesia. Potential risk factors for PAS were recorded in
      1340 consecutive patients. Signs of shivering, peripheral and core temperature,
      and thermal comfort were recorded in the postanesthetic care unit. The data were
      split into an evaluation data set (n = 1000) and a validation data set (n = 340).
      The first was used to identify independent risk factors for PAS and to formulate
      a risk score using backward-elimination logistic regression analysis. The
      proposed model was subsequently tested for its discrimination and calibration
      properties using receiver operating characteristic (ROC)-curve analysis and
      linear correlation between the predicted and the actual incidences of PAS in the
      validation group. The incidence of PAS was 11.6%. There were three major risk
      factors: young age, endoprosthetic surgery, and core hypothermia, with age being
      the most important. The risk score derived from this analysis had a reasonable
      discriminating power, with an area under the ROC-curve of 0.69 (95% confidence
      interval, 0.60-0.78; P < 0.0001). Furthermore the equation of the calibration
      curve (y = 0.69x + 6; R2= 0.82; P < 0.05) indicated a good and statistically
      significant agreement between predicted and actual PAS incidence. Postoperative
      shivering can be predicted with acceptable accuracy using the four risk factors
      identified in the present study. The presented model may serve as a clinical tool
      to help clinicians to rationally administer prophylactic antishivering drugs.

PMID- 16301275
TI  - A multicenter study of the Ambu laryngeal mask in nonparalyzed, anesthetized
      patients.
AB  - We designed this multicenter trial to evaluate the performance and safety of the
      Ambu laryngeal mask, a new disposable supraglottic airway device, in patients
      scheduled for elective surgery. One-hundred-eighteen nonparalyzed, anesthetized
      patients (ASA physical status I-II, age, 18-65 yr, body mass index, 18-30 kg/m(
      2)) receiving total IV anesthesia were included in this study. After device
      insertion, fiberoptic position and oropharyngeal leak pressure were determined at
      an intracuff pressure of 60 cm H2O. Ease of ventilation was determined by
      controlling ventilation at 6 mL/kg tidal volume. Any complications were noted and
      recorded. Device placement was successful in all patients on the first or second
      attempt (92.4% or 7.6%, respectively) with an insertion time (removal of face
      mask until first tidal volume) of 44.9 +/- 37.91 s. Adequate ventilation was
      achieved in all patients and the vocal cords could be visualized by fiberoptic
      endoscopy in 91.5% of patients. Oropharyngeal leak pressures were 24.1 +/- 5.44
      cm H2O. Blood was detected on the device in 8.5% of patients. Complications and
      patient complaints were minor and quickly resolved. The Ambu laryngeal mask is
      easy and quick to insert and provides a safe and efficient seal during positive
      pressure ventilation in nonparalyzed patients scheduled for elective surgery.

PMID- 16301276
TI  - Perioperative management for chronic schizophrenic patients.
AB  - Schizophrenic patients are at increased risk for perioperative complications, as
      their biological response to stress is impaired. The increased complications are
      associated with physical disorders, antipsychotic or hazardous health behaviors,
      and interactions between antipsychotics and anesthetic drugs. Thus,
      anesthesiologists must not only be aware of the perioperative problems of these
      patients but must also learn how to manage their perioperative course.

PMID- 16301277
TI  - The relationship between salivary biomarkers and state-trait anxiety inventory
      score under mental arithmetic stress: a pilot study.
AB  - Measurement of stress hormones is a common objective method for assessment of
      mental stress. However, the stress of blood sampling alone may also increase
      stress hormone levels. In the present study, we sampled salivary biomarkers from
      healthy volunteers under noninvasive conditions and determined their efficacy to
      assess mental stress. Specifically, we examined the relationship between State
      Anxiety Inventory score (STAI-s) in subjects exposed to arithmetic stress and
      salivary chromogranin-A, alpha-amylase, or cortisol. The STAI-s was significantly
      correlated to salivary alpha-amylase (r = 0.589; P < 0.01) but not to salivary
      chromogranin-A or cortisol. Therefore, salivary alpha-amylase is a useful
      indicator of psychosocial stress.

PMID- 16301278
TI  - The Cohen flexitip endobronchial blocker: an alternative to a double lumen tube.
AB  - One-lung ventilation (OLV) is usually achieved by the use of a double-lumen tubes
      (DLTs). With increasing need for use of OLV for video-assisted thoracoscopic
      procedures, the limitations of traditional DLT's, including difficult insertion
      and positioning, have become evident. This has led to renewed interest in
      devising alternative methods of achieving lung separation, such as the Univent
      tube or Arndt endobronchial blocker. This report describes the technical features
      and clinical use of a new tip-deflecting endobronchial blocker.

PMID- 16301279
TI  - The evidence that deep anesthesia impacts long term mortality is not compelling.

PMID- 16301280
TI  - Bilateral giant posterior laryngeal granulomas with dyspnea: a rare complication
      of endotracheal intubation.

PMID- 16301281
TI  - Through-the-LMA fiberoptic intubation of the trachea in a patient with an
      unexpected difficult airway.

PMID- 16301282
TI  - Tetraplegia after coronary artery bypass grafting in a patient with undiagnosed
      cervical stenosis.

PMID- 16301283
TI  - The combination of tramadol and morphine may be recommended for postoperative
      analgesia.

PMID- 16301284
TI  - Carotid endarterectomy using single injection posterior cervical paravertebral
      block.

PMID- 16301285
TI  - What is the appropriate anticoagulation therapy in patients with a history of
      heparin-induced thrombocytopenia?

PMID- 16301286
TI  - Major post-partum hemorrhage and treatment with recombinant factor VIIa.

PMID- 16301287
TI  - Treatment of postoperative nausea and vomiting with dolasetron versus
      ondansetron: is there a conflict of interest?

PMID- 16301288
TI  - The LMA is a critical rescue device in airway emergencies.

PMID- 16301289
TI  - Web-based data collection: security is only as good as the weakest link.

PMID- 16301290
TI  - Allogeneic blood transfusion and wound healing disturbance after orthopaedic
      surgery.

PMID- 16301291
TI  - An unusual cause of faulty Tec 7 vaporizer.

PMID- 16301292
TI  - Thoracic epidural anesthesia in pediatric liver transplantation.

PMID- 16301293
TI  - Intraduodenal milk injection after induction of general anesthesia is safe and
      useful during surgical treatment for intractable chylothorax.

PMID- 16301294
TI  - Retrograde submental intubation after faciomaxillary trauma.

PMID- 16301295
TI  - Severe metabolic acidosis secondary to organophosphate poisoning.

PMID- 16301296
TI  - Quantifying ascertainment bias and species-specific length differences in human
      and chimpanzee microsatellites using genome sequences.
AB  - Surveys of variability of homologous microsatellite loci among species reveal an
      ascertainment bias for microsatellite length where microsatellite loci isolated
      in one species tend to be longer than homologous loci in related species. Here,
      we take advantage of the availability of aligned human and chimpanzee genome
      sequences to compare length difference of homologous microsatellites for loci
      identified in humans to length difference for loci identified in chimpanzees. We
      are able to quantify ascertainment bias for a range of motifs and microsatellite
      lengths. Because ascertainment bias should not exist if a microsatellite selected
      in one species is as likely to be longer as it is to be shorter than its
      homologue, we propose that the nature of ascertainment bias can provide evidence
      for understanding how microsatellites evolve. We show that bias is greater for
      longer microsatellites but also that many long microsatellites have short
      homologues. These results are consistent with the notion that growth of long
      microsatellites is constrained by an upper length boundary that, when reached,
      sometimes results in large deletions. By evaluating ascertainment bias separately
      for interrupted and uninterrupted repeats we also show that long microsatellites
      tend to become interrupted, thereby contributing a second component of
      ascertainment bias. Having accounted for ascertainment bias, in agreement with
      results published elsewhere, we find that microsatellites in humans are longer on
      average than those in chimpanzees. This length difference is similar among repeat
      motifs but surprisingly comprises two roughly equal components, one associated
      with the repeats themselves and one with the flanking sequences. The differences
      we find can only be explained if microsatellites are both evolving directionally
      under a biased mutation process and are doing so at different rates in different
      closely related species.

PMID- 16301297
TI  - Pulmonary physicians in the practice of sleep medicine.

PMID- 16301298
TI  - Intensive insulin therapy in critical illness.

PMID- 16301299
TI  - Reevaluating neonatal resuscitation with 100% oxygen.

PMID- 16301300
TI  - Once upon a time. . . improved intermittent therapy for tuberculosis--fact or
      fable?

PMID- 16301301
TI  - ATS/ERS statement: raised volume forced expirations in infants: guidelines for
      current practice.

PMID- 16301302
TI  - Antibiotic therapy and outcome in critically ill patients with pneumococcal
      bacteremia.

PMID- 16301303
TI  - Potential mechanisms for mortality reduction associated with combination
      antibiotic therapy among severely ill patients with pneumococcal bacteremia.

PMID- 16301304
TI  - Is combination the only issue?

PMID- 16301305
TI  - Progressive decline in FRC in infants: physiology or technology?

PMID- 16301306
TI  - Use and misuse of a discount voucher scheme as a subsidy for insecticide-treated
      nets for malaria control in southern Tanzania.
AB  - Since 1997, discount vouchers for insecticide-treated nets (ITNs) have been used
      in two rural districts of southern Tanzania as a way to target subsidies to
      children under 5 years and pregnant women. We assessed appropriate use and misuse
      of discount vouchers through a follow-up study of 104 randomly selected vouchers.
      We traced these vouchers from their original issue in mother-and-child health
      (MCH) clinics through to being redeemed at a sales agent. We found that all
      vouchers that reached the target population (100%, 56/56) were used to buy an
      ITN. Moreover, 94% of the ITNs bought with vouchers were used by those intended,
      women and children under 5 years. However, up to 48% (50/104) of the vouchers had
      been misused at the clinics that issued them. Nevertheless, large-scale misuse
      occurred only at three of 21 clinics. Although most women slept under a net while
      pregnant, the use of voucher-subsidized ITNs during pregnancy was low despite
      widespread knowledge of the scheme. Parents had apparently decided to buy the
      subsidized ITNs once the child was born and not during pregnancy. Importantly, in
      20% of households the only existing net had been bought with a voucher. Our
      findings suggest that vouchers are properly used by the target population, and
      that to minimize voucher leakage, control measures are needed at MCH clinics and
      to a certain extent for commercial sales agents. Increased awareness among the
      whole community on the right to receive a discount voucher may also help to
      control misuse at health facilities.

PMID- 16301307
TI  - Do malaria preventive interventions reach the poor? Socioeconomic inequities in
      expenditure on and use of mosquito control tools in Sudan.
AB  - OBJECTIVES: To determine levels of socioeconomic inequities in the prevention of
      malaria, and to examine the implications of the findings for improving the
      equitable control of malaria in the Sudan. METHODS: A cross-sectional survey
      using a pre-tested interviewer-administered questionnaire was administered to 720
      randomly selected householders from six localities in Gezira and Khartoum States.
      A socioeconomic status (SES) index, which was developed using principal
      components analysis, was used to examine socioeconomic inequity in the prevention
      of malaria. FINDINGS: Socioeconomic status was positively related to expenditures
      and use of vector control tools. The poorest households spent the least amounts
      of money to prevent malaria and were the least likely to own mosquito nets.
      CONCLUSION: The inequity in the prevention of malaria in the study areas has to
      be redressed before malaria can be effectively controlled in Sudan. Malaria
      control managers should continually determine the extent to which malaria
      preventive tools reach the poorest socioeconomic groups, and fashion strategies
      that will ensure that equity is always maintained.

PMID- 16301308
TI  - Hybrid hierarchical clustering with applications to microarray data.
AB  - In this paper, we propose a hybrid clustering method that combines the strengths
      of bottom-up hierarchical clustering with that of top-down clustering. The first
      method is good at identifying small clusters but not large ones; the strengths
      are reversed for the second method. The hybrid method is built on the new idea of
      a mutual cluster: a group of points closer to each other than to any other
      points. Theoretical connections between mutual clusters and bottom-up clustering
      methods are established, aiding in their interpretation and providing an
      algorithm for identification of mutual clusters. We illustrate the technique on
      simulated and real microarray datasets.

PMID- 16301309
TI  - Intrinsic protein disorder, amino acid composition, and histone terminal domains.
AB  - Core and linker histones are the most abundant protein components of chromatin.
      Even though they lack intrinsic structure, the N-terminal "tail" domains (NTDs)
      of the core histones and the C-terminal tail domain (CTD) of linker histones bind
      to many different macromolecular partners while functioning in chromatin. Here we
      discuss the underlying physicochemical basis for how the histone terminal domains
      can be disordered and yet specifically recognize and interact with different
      macromolecules. The relationship between intrinsic disorder and amino acid
      composition is emphasized. We also discuss the potential structural consequences
      of acetylation and methylation of lysine residues embedded in intrinsically
      disordered histone tail domains.

PMID- 16301310
TI  - The copper-enzyme family of dopamine beta-monooxygenase and peptidylglycine alpha
      hydroxylating monooxygenase: resolving the chemical pathway for substrate
      hydroxylation.

PMID- 16301311
TI  - Modulation of monocarboxylic acid transporter-1 kinetic function by the cAMP
      signaling pathway in rat brain endothelial cells.
AB  - MCT1 (monocarboxylic acid transporter 1) facilitates bidirectional monocarboxylic
      acid transport across membranes. MCT1 function and regulation have not been
      characterized previously in cerebral endothelial cells but may be important
      during normal cerebral energy metabolism and during brain diseases such as
      stroke. Here, by using the cytoplasmic pH indicator 2',7'-bis-(2-carboxyethyl)-5
      (and-6)-carboxyfluorescein-acetoxymethyl ester, the initial rates of
      monocarboxylate-dependent cytoplasmic acidification were measured as an
      indication of MCT1 kinetic function in vitro using the rat brain endothelial cell
      (RBE4) model of blood-brain transport. The initial rate of L-lactate-dependent
      acidification was significantly inhibited by 5-10-min incubations with agonists
      of intracellular cAMP-dependent cell signaling pathways as follows: dibutyryl
      cAMP, forskolin, and isoproterenol. Isoproterenol reduced V(max) but did not
      affect K(m) values. The effects of forskolin were completely reversed by the
      protein kinase A inhibitor H89, whereas H89 alone increased transport rates.
      Cytoplasmic cAMP levels, measured by radioimmunoassay, were increased by
      forskolin or isoproterenol, and the effect of isoproterenol was inhibited by
      propranolol. MCT1-independent intracellular pH control mechanisms did not
      contribute to the forskolin or H89 effects on MCT1 kinetic function as determined
      with amiloride, monocarboxylate-independent acid loading, or the transport
      inhibitor alpha-cyano-4-hydroxycinnamate. The data demonstrate the direct
      modulation of MCT1 kinetic function in cerebral endothelial cells by agents known
      to affect the beta-adrenergic receptor/adenylyl cyclase/cAMP/protein kinase A
      intracellular signaling pathway.

PMID- 16301312
TI  - The first glycosynthase derived from an inverting glycoside hydrolase.
AB  - Reducing end xylose-releasing exooligoxylanase (Rex, EC 3.2.1.156) is an
      inverting GH that hydrolyzes xylooligosaccharides (> or = X3) to release X1 at
      their reducing end. The wild-type enzyme exhibited the Hehre resynthesis
      hydrolysis mechanism, in which alpha-X2F was hydrolyzed to X2 and HF in the
      presence of X1 as an acceptor molecule. However, the transglycosidation product
      (X3) was not detectable in the reaction. To convert reducing end xylose-releasing
      exooligoxylanase to glycosynthase, derivatives with mutations in the catalytic
      base (Asp-263) were constructed by saturation random mutagenesis. Nine amino acid
      residue mutants (Asp-263 to Gly, Ala, Val, Thr, Leu, Asn, Cys, Pro, or Ser) were
      found to possess glycosynthase activity forming X3 from alpha-X2F and X1. Among
      them, D263C showed the highest level of X3 production, and D263N exhibited the
      fastest consumption of alpha-X2F. The D263C mutant showed 10-fold lower
      hydrolytic activity than D263N, resulting in the highest yield of X3. X2 was
      formed from the early stage of the reaction of the D263C mutant, indicating that
      a portion of the X3 formed by condensation was hydrolyzed before its release from
      the enzyme. To acquire glycosynthase activity from inverting enzymes, it is
      important to minimize the decrease in F(-)-releasing activity while maximizing
      the decrease in the hydrolytic activity. The present study expands the
      possibility of conversion of glycosynthases from inverting enzymes.

PMID- 16301313
TI  - Formation of a distinctive complex between the inducible bacterial lysine
      decarboxylase and a novel AAA+ ATPase.
AB  - AAA+ ATPases are ubiquitous proteins that employ the energy obtained from ATP
      hydrolysis to remodel proteins, DNA, or RNA. The MoxR family of AAA+ proteins is
      widespread throughout bacteria and archaea but is largely uncharacterized.
      Limited work with specific members has suggested a potential role as molecular
      chaperones involved in the assembly of protein complexes. As part of an effort
      aimed at determining the function of novel AAA+ chaperones in Escherichia coli,
      we report the characterization of a representative member of the MoxR family,
      YieN, which we have renamed RavA (regulatory ATPase variant A). We show that the
      ravA gene exists on an operon with another gene encoding a protein, YieM, of
      unknown function containing a Von Willebrand Factor Type A domain. RavA
      expression is under the control of the sigmaS transcription factor, and its
      levels increase toward late log/early stationary phase, consistent with its
      possible role as a general stress-response protein. RavA functions as an ATPase
      and forms hexameric oligomers. Importantly, we demonstrate that RavA interacts
      strongly with inducible lysine decarboxylase (LdcI or CadA) forming a large cage
      like structure consisting of two LdcI decamers linked by a maximum of five RavA
      oligomers. Surprisingly, the activity of LdcI does not appear to be affected by
      binding to RavA in a number of in vitro and in vivo assays, however, complex
      formation results in the stimulation of RavA ATPase activity. Data obtained
      suggest that the RavA-LdcI interaction may be important for the regulation of
      RavA activity against its targets.

PMID- 16301314
TI  - Alpha-latrotoxin induces exocytosis by inhibition of voltage-dependent K+
      channels and by stimulation of L-type Ca2+ channels via latrophilin in beta
      cells.
AB  - The spider venom alpha-latrotoxin (alpha-LTX) induces massive exocytosis after
      binding to surface receptors, and its mechanism is not fully understood. We have
      investigated its action using toxin-sensitive MIN6 beta-cells, which express
      endogenously the alpha-LTX receptor latrophilin (LPH), and toxin-insensitive HIT
      T15 beta-cells, which lack endogenous LPH. alpha-LTX evoked insulin exocytosis in
      HIT-T15 cells only upon expression of full-length LPH but not of LPH truncated
      after the first transmembrane domain (LPH-TD1). In HIT-T15 cells expressing full
      length LPH and in native MIN6 cells, alpha-LTX first induced membrane
      depolarization by inhibition of repolarizing K(+) channels followed by the
      appearance of Ca(2+) transients. In a second phase, the toxin induced a large
      inward current and a prominent increase in intracellular calcium ([Ca(2+)](i))
      reflecting pore formation. Upon expression of LPH-TD1 in HIT-T15 cells just this
      second phase was observed. Moreover, the mutated toxin LTX(N4C), which is devoid
      of pore formation, only evoked oscillations of membrane potential by reversible
      inhibition of iberiotoxin-sensitive K(+) channels via phospholipase C, activated
      L-type Ca(2+) channels independently from its effect on membrane potential, and
      induced an inositol 1,4,5-trisphosphate receptor-dependent release of
      intracellular calcium in MIN6 cells. The combined effects evoked transient
      increases in [Ca(2+)](i) in these cells, which were sensitive to inhibitors of
      phospholipase C, protein kinase C, or L-type Ca(2+) channels. The latter agents
      also reduced toxin-induced insulin exocytosis. In conclusion, alpha-LTX induces
      signaling distinct from pore formation via full-length LPH and phospholipase C to
      regulate physiologically important K(+) and Ca(2+) channels as novel targets of
      its secretory activity.

PMID- 16301315
TI  - Function and evolution of a mosquito salivary protein family.
AB  - Saliva of blood-sucking arthropods contains a complex and diverse mixture of
      antihemostatic, antiinflammatory, and immunomodulatory compounds. The D7 salivary
      family of proteins is abundantly expressed in blood-feeding Diptera and is
      distantly related to the odorant-binding protein superfamily. In mosquitoes, two
      subfamilies exist, the long and short D7 proteins. Ticks and kissing bugs evolved
      salivary lipocalins that act as efficient scavengers of biogenic amines, and a
      similar function was postulated for the D7 proteins. Accordingly, we expressed
      the five members of the small D7 family of the African malaria vector Anopheles
      gambiae and a D7 long form from Aedes aegypti and showed by isothermal
      microcalorimetry, a modified and very sensitive non-equilibrium
      chromatography/spectrum distortion method, and by smooth muscle bioassay that
      four of these five short D7 proteins and the D7 long form bind serotonin with
      high affinity, as well as histamine and norepinephrine. The nonbinding D7 protein
      is poorly expressed in the salivary glands and appears to be on the path to
      becoming a pseudogene. Scavenging of host amines would antagonize their
      vasoconstrictor, platelet-aggregating, and pain-inducing properties. It appears
      that counteracting biogenic amines is of strong adaptive value in the convergent
      evolution of arthropods to hematophagy. This adaptation has been solved
      independently in ticks, bugs, and mosquitoes by co-option of either member of the
      lipocalin or, as shown here, by the odorant-binding protein families.

PMID- 16301316
TI  - Mon2, a relative of large Arf exchange factors, recruits Dop1 to the Golgi
      apparatus.
AB  - The protein Mon2 is distantly related to the guanine nucleotide exchange factors
      (GEFs) that activate Arf1 on Golgi membranes. However, unlike these "large" Arf
      GEFs, Mon2 lacks the Sec7 domain that catalyzes nucleotide exchange on Arf1. Here
      we report that yeast Mon2 shares extensive homology with the noncatalytic parts
      of both the BIG and Golgi brefeldin A resistance factor subfamilies of Arf GEFs
      and is located to the trans-Golgi. Moreover, we find that Mon2 forms a complex
      with Dop1, a large cytoplasmic protein conserved in evolution from humans to
      protozoa. Deletion of Mon2 results in mislocalization of Dop1 from the Golgi and
      defects in cycling between endosomes and the Golgi. However, unlike Mon2, Dop1 is
      essential for yeast viability. A conditional allele of Dop1 shows that loss of
      Dop1 activity not only affects endosome to Golgi transport but also causes a
      severe perturbation of the organization of the endoplasmic reticulum. Thus, it
      appears that Dop1 plays a widespread role in membrane organization, and Mon2 acts
      as a scaffold to recruit the Golgi-localized pool of Dop1.

PMID- 16301317
TI  - The role of properdin in the assembly of the alternative pathway C3 convertases
      of complement.
AB  - Complement is a powerful host defense system that contributes to both innate and
      acquired immunity. There are three pathways of complement activation, the
      classical pathway, lectin pathway, and alternative pathway. Each generates a C3
      convertase, a serine protease that cleaves the central complement protein, C3.
      Nearly all the biological consequences of complement are dependent on the
      resulting cleavage products. Properdin is a positive regulator of complement
      activation that stabilizes the alternative pathway convertases (C3bBb). Properdin
      is composed of multiple identical protein subunits, with each subunit carrying a
      separate ligand-binding site. Previous reports suggest that properdin function
      depends on multiple interactions between its subunits with its ligands. In this
      study I used surface plasmon resonance assays to examine properdin interactions
      with C3b and factor B. I demonstrated that properdin promotes the association of
      C3b with factor B and provides a focal point for the assembly of C3bBb on a
      surface. I also found that properdin binds to preformed alternative pathway C3
      convertases. These findings support a model in which properdin, bound to a target
      surface via C3b, iC3b, or other ligands, can use its unoccupied C3b-binding sites
      as receptors for nascent C3b, bystander C3b, or pre-formed C3bB and C3bBb
      complexes. New C3bP and C3bBP intermediates can lead to in situ assembly of
      C3bBbP. The full stabilizing effect of properdin on C3bBb would be attained as
      properdin binds more than one ligand at a time, forming a lattice of properdin:
      ligand interactions bound to a surface scaffold.

PMID- 16301318
TI  - Changes in cytosolic Ca2+ levels regulate Bcl-xS and Bcl-xL expression in
      spermatogenic cells during apoptotic death.
AB  - Bcl-x exists in two isoforms, the anti-apoptotic form Bcl-xL and the proapoptotic
      form Bcl-xS. The critical balance between the two forms appears to be important
      for cell survival; however, it is still not clear exactly how the vital balance
      is maintained. Using an in vitro spermatogenic cell apoptosis model, this study
      provides a new insight into the possible role of Ca2+ in regulating the Bcl-xS
      and Bcl-xL expression. 2,5-Hexanedione, a metabolite of the common industrial
      solvent n-hexane, caused a significant increase in reactive oxygen species
      followed by an enhancement of intracellular Ca2+ through the T-type Ca2+
      channels. Consequent to the above changes, expression of Bcl-xS increased with a
      concomitant drop in Bcl-xL expression, thus altering the ratio of the two
      proteins. Impediment of Ca2+ influx by using a T-type Ca2+ channel blocker
      pimozide resulted in a decrease in Bcl-xS and an increase in Bcl-xL expression.
      This caused prevention of mitochondrial potential loss, reduction of caspase-3
      activity, inhibition of DNA fragmentation, and increase in cell survival.
      Alternatively, Ca2+ ionophores caused an increase of Bcl-xS encoding isoform over
      the Bcl-xL-encoding isoform. Therefore, this study proposes a role for Ca2+ in
      regulation of Bcl-xS and Bcl-xL expression and ultimately cell fate.

PMID- 16301319
TI  - Erbin inhibits RAF activation by disrupting the sur-8-Ras-Raf complex.
AB  - Erbin is a member of the LAP (leucine-rich repeat (LRR) and PDZ domain) family.
      It inhibits Ras-mediated activation of ERK in response to growth factors. In this
      study, we investigated the mechanisms by which Erbin regulates the Ras-Raf-MEK
      pathway. The N-terminal LRR domain was necessary and sufficient to inhibit
      neuregulin-activated expression of epsilon416-Luc, a reporter of ERK activation.
      On the other hand, Erbin had no effect on Ras activation, but it attenuated
      neuregulin-induced Raf activation, suggesting that Erbin may regulate Raf
      activation by Ras. Via the LRR domain, Erbin interacts with Sur-8, a scaffold
      protein necessary for the Ras-Raf complex. Expression of Erbin attenuated the
      interaction of Sur-8 with active Ras and Raf. Moreover, Erbin-shRNA, which
      suppressed Erbin expression at mRNA and protein levels, increased the interaction
      of Sur-8 with Ras and Raf, ERK activation, and neuregulin-induced expression of
      endogenous acetylcholine receptor epsilon-subunit mRNA. These results demonstrate
      a regulatory role of Erbin in the Ras-Raf-MEK pathway, suggesting that Erbin may
      inhibit ERK activation by disrupting the Sur-8-Ras/Raf interaction.

PMID- 16301320
TI  - Phosphorylation of P-Rex1 by the cyclic AMP-dependent protein kinase inhibits the
      phosphatidylinositiol (3,4,5)-trisphosphate and Gbetagamma-mediated regulation of
      its activity.
AB  - Rac activation is a key step in chemotaxis of hematopoietic cells, which is both
      positively and negatively regulated by receptors coupled to heterotrimeric G
      proteins. P-Rex1, a Rac-specific guanine nucleotide exchange factor, is dually
      activated by phosphatidylinositol (3,4,5)-trisphosphate (PIP(3)) and the
      Gbetagamma subunits of heterotrimeric G proteins. This study explored the
      regulation of P-Rex1 by phosphorylation with the cAMP-dependent protein kinase
      (protein kinase A) in vitro and by G(i)- and G(s)-coupled receptors in HEK293T
      cells. P-Rex1 isolated from Sf9 and HEK293T cells migrates as two distinct bands
      that are partially phosphorylated. Phosphorylation of P-Rex1 with protein kinase
      A (PKA) inhibits the PIP(3)- and Gbetagamma-stimulated P-Rex1 guanine nucleotide
      exchange activity on Rac. The guanine nucleotide exchange factor activity of
      three different forms of P-Rex1 (native Sf9, de-phosphorylated, and
      phosphorylated) was examined in the presence of PIP(3) and varying concentrations
      of Gbeta(1)gamma(2). Gbeta(1)gamma(2) was 47-fold less potent in activating the
      phosphorylated form of P-Rex1 compared with the de-phosphorylated form. HEK293T
      cells expressing P-Rex1 were labeled with (32)P and stimulated with
      lysophosphatidic acid (LPA) to release Gbetagamma or isoproterenol to activate
      PKA. Treatment with isoproterenol or S(p)-cAMPS, a potent activator of PKA,
      increased the incorporation of (32)P into P-Rex1. LPA increased the amount of GTP
      bound Rac in the cells and isoproterenol reduced basal levels of GTP-bound Rac
      and blunted the effect of LPA. Treatment of the cells with S(p)-cAMPS also
      reduced the levels of GTP-bound Rac. These results outline a novel mechanism for
      G(s)-linked receptors to regulate the function of P-Rex1 and inhibit its function
      in cells.

PMID- 16301321
TI  - Differential sensitivity of P-Rex1 to isoforms of G protein betagamma dimers.
AB  - P-Rex1 is a specific guanine nucleotide exchange factor (GEF) for Rac, which is
      present in high abundance in brain and hematopoietic cells. P-Rex1 is dually
      regulated by phosphatidylinositol (3,4,5)-trisphosphate and the Gbetagamma
      subunits of heterotrimeric G proteins. We examined which of the multiple G
      protein alpha and betagamma subunits activate P-Rex1-mediated Rac guanine
      nucleotide exchange using pure, recombinant proteins reconstituted into synthetic
      lipid vesicles. AlF(-)(4) activated G(s),G(i),G(q),G(12), or G(13) alpha subunits
      were unable to activate P-Rex1. Gbetagamma dimers containing Gbeta(1-4) complexed
      with gamma(2) stimulated P-Rex1 activity with EC(50) values ranging from 10 to 20
      nm. Gbeta(5)gamma(2) was not able to stimulate P-Rex1 GEF activity. Dimers
      containing the beta(1) subunit complexed with a panel of different Ggamma
      subunits varied in their ability to stimulate P-Rex1. The beta(1)gamma(3),
      beta(1)gamma(7), beta(1)gamma(10), and beta(1)gamma(13HA) dimers all activated P
      Rex1 with EC(50) values ranging from 20 to 38 nm. Dimers composed of
      beta(1)gamma(12) had lower EC(50) values (approximately 112 nm). The farnesylated
      gamma(11) subunit is highly expressed in hematopoietic cells; surprisingly,
      dimers containing this subunit (beta(1)gamma(11)) were also less effective at
      activating P-Rex1. These findings suggest that the composition of the Gbetagamma
      dimer released by receptor activation may differentially activate P-Rex1.

PMID- 16301322
TI  - Structural changes of region 1-16 of the Alzheimer disease amyloid beta-peptide
      upon zinc binding and in vitro aging.
AB  - Amyloid deposits within the cerebral tissue constitute a characteristic lesion
      associated with Alzheimer disease. They mainly consist of the amyloid peptide
      Abeta and display an abnormal content in Zn(2+) ions, together with many
      truncated, isomerized, and racemized forms of Abeta. The region 1-16 of Abeta can
      be considered the minimal zinc-binding domain and contains two aspartates subject
      to protein aging. The influence of zinc binding and protein aging related
      modifications on the conformation of this region of Abeta is of importance given
      the potentiality of this domain to constitute a therapeutic target, especially
      for immunization approaches. In this study, we determined from NMR data the
      solution structure of the Abeta-(1-16)-Zn(2+) complex in aqueous solution at pH
      6.5. The residues His(6), His(13), and His(14) and the Glu(11) carboxylate were
      identified as ligands that tetrahedrally coordinate the Zn(II) cation. In vitro
      aging experiments on Abeta-(1-16) led to the formation of truncated and
      isomerized species. The major isomer generated, Abeta-(1-16)-l-iso-Asp(7),
      displayed a local conformational change in the His(6)-Ser(8) region but kept a
      zinc binding propensity via a coordination mode involving l-iso-Asp(7). These
      results are discussed here with regard to Abeta fibrillogenesis and the
      potentiality of the region 1-16 of Abeta to be used as a therapeutic target.

PMID- 16301324
TI  - Complement regulatory protein Crry/p65-mediated signaling in T lymphocytes: role
      of its cytoplasmic domain and partitioning into lipid rafts.
AB  - Crry/p65 is a type I glycoprotein, which protects mouse T cells from complement
      attack. We have previously shown that complement receptor I-related protein
      Crry/p65 (Crry) ligation has a costimulatory effect on mouse CD4+ T cell
      activation. Here, we have examined the mechanisms responsible for Crry
      costimulation, addressing the question of whether Crry potentiates signal
      transduction starting at the T cell receptor (TCR)/CD3 complex or promotes
      distinct costimulatory signals. We show that Crry increases early TCR-dependent
      activation signals, including p56lck-, zeta-associated protein-70 (ZAP-70), Vav
      1, Akt, and extracellular signal-regulated kinase (ERK) phosphorylation but also
      costimulation-dependent mitogen-activated protein kinases (MAPK), such as the
      stress-activated c-Jun N-terminal kinase (JNK). It is intriguing that Crry
      costimulus enhanced p38 MAPK activation in T helper cell type 1 (Th1) but not in
      Th2 cells. A fraction of Crry is found consistently in the detergent-insoluble
      membrane fraction of Th1 or Th2 cells or CD4+ lymphoblasts. Crry costimulation
      induced clustering of lipid rafts, increasing their content in Crry, CD3epsilon,
      and p59-60 forms of p56lck, and caused actin polymerization close to the site of
      activation in Th2 cells. Such events were inhibited by wortmannin, suggesting a
      role for phosphatidylinositol-3 kinase in these effects. The Crry cytoplasmic
      domain was required for JNK activation and interleukin-4 secretion but not for
      the presence of Crry in rafts or activation of p56lck, ZAP-70, Akt, Vav-1, or
      ERK. This suggests that Crry costimulation involves two different but not
      mutually exclusive signal transduction modules. The dual function of Crry as a
      complement regulatory protein and as a T cell costimulator illustrates the
      importance of complement regulatory proteins as links between innate and adaptive
      immunity.

PMID- 16301325
TI  - Phagocytosis stimulates mobilization and shedding of intracellular CD16A in human
      monocytes and macrophages: inhibition by HIV-1 infection.
AB  - Surface and intracellular staining coupled with flow cytometric analysis was used
      to show for the first time that human macrophages and a minor subset of
      peripheral blood monocytes have an internal pool of CD16A, which is mobilized and
      shed during Fc receptor for immunoglobulin G-mediated phagocytosis. Human
      immunodeficiency virus type 1 (HIV-1) infection of monocyte-derived macrophages
      in vitro led to a reduction in the phagocytosis-induced up-regulation in CD16A
      shedding. These results suggest that monocytes and macrophages may be a source of
      soluble CD16A, which is elevated in the serum of patients in a variety of disease
      states and that the mobilization and shedding of CD16A in response to
      phagocytosis are disrupted by HIV-1 infection.

PMID- 16301326
TI  - Shiga toxin 1-induced cytokine production is mediated by MAP kinase pathways and
      translation initiation factor eIF4E in the macrophage-like THP-1 cell line.
AB  - Upon binding to the glycolipid receptor globotriaosylceramide, Shiga toxins
      (Stxs) undergo retrograde transport to reach ribosomes, cleave 28S rRNA, and
      inhibit protein synthesis. Stxs induce the ribotoxic stress response and cytokine
      and chemokine expression in some cell types. Signaling mechanisms necessary for
      cytokine expression in the face of toxin-mediated protein synthesis inhibition
      are not well characterized. Stxs may regulate cytokine expression via multiple
      mechanisms involving increased gene transcription, mRNA transcript stabilization,
      and/or increased translation initiation efficiency. We show that treatment of
      differentiated THP-1 cells with purified Stx1 resulted in prolonged activation of
      c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK)
      cascades, and lipopolysaccharides (LPS) rapidly triggered transient activation of
      JNK and p38 and prolonged activation of extracellular signal-regulated kinase
      cascades. Simultaneous treatment with Stx1 + LPS mediated prolonged p38 MAPK
      activation. Stx1 increased eukaryotic translation initiation factor 4E (eIF4E)
      activation by 4.3-fold within 4-6 h, and LPS or Stx1 + LPS treatment increased
      eIF4E activation by 7.8- and 11-fold, respectively, within 1 h. eIF4E activation
      required Stx1 enzymatic activity and was mediated by anisomycin, another
      ribotoxic stress inducer. A combination of MAPK inhibitors or a MAPK-interacting
      kinase 1 (Mnk1)-specific inhibitor blocked eIF4E activation by all stimulants.
      Mnk1 inhibition blocked the transient increase in total protein synthesis
      detected in Stx1-treated cells but failed to block long-term protein synthesis
      inhibition. The MAPK inhibitors or Mnk1 inhibitor blocked soluble interleukin
      (IL)-1beta and IL-8 production or release by 73-96%. These data suggest that Stxs
      may regulate cytokine expression in part through activation of MAPK cascades,
      activation of Mnk1, and phosphorylation of eIF4E.

PMID- 16301327
TI  - The IgD-binding domain of the Moraxella IgD-binding protein MID (MID962-1200)
      activates human B cells in the presence of T cell cytokines.
AB  - Moraxella catarrhalis immunoglobulin D (IgD)-binding protein (MID) is an outer
      membrane protein with specific affinity for soluble and cell-bound human IgD.
      Here, we demonstrate that mutated M. catarrhalis strains devoid of MID show a 75%
      decreased activation of human B cells as compared with wild-type bacteria. In
      contrast to MID-expressing Moraxella, the MID-deficient Moraxella mutants did not
      bind to human CD19+ IgD+ B cells. The smallest MID fragment with preserved IgD
      binding capacity comprises 238 amino acids (MID(962-1200)). To prove the
      specificity of MID(962-1200) for IgD, a Chinese hamster ovary (CHO) cell line
      expressing membrane-anchored human IgD was manufactured. MID(962-1200) bound
      strongly to the recombinant IgD on CHO cells. Moreover, MID(962-1200) stimulated
      peripheral blood lymphocyte (PBL) proliferation 5- and 15-fold at 0.1 and 1.0
      microg/ml, respectively. This activation could be blocked completely by
      antibodies directed against the CD40 ligand (CD154). MID(962-1200) also activated
      purified B cells in the presence of interleukin (IL)-2 or IL-4. An increased IL-6
      production was seen after stimulation with MID(962-1200), as revealed by a human
      cytokine protein array. MID(962-1200) fused to green fluorescent protein (GFP)
      bound to human B cells and activated PBL to the same degree as MID(962-1200).
      Taken together, MID is the only IgD-binding protein in Moraxella. Furthermore,
      the novel T cell-independent antigen MID(962-1200) may, together with MID(962
      1200)-GFP, be considered as promising reagents in the study of IgD-dependent B
      cell activation.

PMID- 16301328
TI  - Signal-mediated export of proteins from the malaria parasite to the host
      erythrocyte.
AB  - Intracellular parasites from the genus Plasmodium reside and multiply in a
      variety of cells during their development. After invasion of human erythrocytes,
      asexual stages from the most virulent malaria parasite, P. falciparum,
      drastically change their host cell and export remodelling and virulence proteins.
      Recent data demonstrate that a specific NH(2)-terminal signal conserved across
      the genus Plasmodium plays a central role in this export process.

PMID- 16301329
TI  - The conserved kinase NHK-1 is essential for mitotic progression and unifying
      acentrosomal meiotic spindles in Drosophila melanogaster.
AB  - Conventional centrosomes are absent from the spindle in female meiosis in many
      species, but it is not clear how multiple chromosomes form one shared bipolar
      spindle without centrosomes. We identified a female sterile mutant in which each
      bivalent chromosome often forms a separate bipolar metaphase I spindle. Unlike
      wild type, prophase I chromosomes fail to form a single compact structure within
      the oocyte nucleus, although the integrity of metaphase I chromosomes appears to
      be normal. Molecular analysis indicates that the mutant is defective in the
      conserved kinase nucleosomal histone kinase-1 (NHK-1). Isolation of further
      alleles and RNA interference in S2 cells demonstrated that NHK-1 is also required
      for mitotic progression. NHK-1 itself is phosphorylated in mitosis and female
      meiosis, suggesting that this kinase is part of the regulatory system
      coordinating progression of mitosis and meiosis.

PMID- 16301330
TI  - Coordinated transport of phosphorylated amyloid-beta precursor protein and c-Jun
      NH2-terminal kinase-interacting protein-1.
AB  - The transmembrane protein amyloid-beta precursor protein (APP) and the vesicle
      associated protein c-Jun NH(2)-terminal kinase-interacting protein-1 (JIP-1) are
      transported into axons by kinesin-1. Both proteins may bind to kinesin-1 directly
      and can be transported separately. Because JIP-1 and APP can interact, kinesin-1
      may recruit them as a complex, enabling their cotransport. In this study, we
      tested whether APP and JIP-1 are transported together or separately on different
      vesicles. We found that, within the cellular context, JIP-1 preferentially
      interacts with Thr(668)-phosphorylated APP (pAPP), compared with
      nonphosphorylated APP. In neurons, JIP-1 colocalizes with vesicles containing
      pAPP and is excluded from those containing nonphosphorylated APP. The
      accumulation of JIP-1 and pAPP in neurites requires kinesin-1, and the expression
      of a phosphomimetic APP mutant increases JIP-1 transport. Down-regulation of JIP
      1 by small interfering RNA specifically impairs transport of pAPP, with no effect
      on the trafficking of nonphosphorylated APP. These results indicate that the
      phosphorylation of APP regulates the formation of a pAPP-JIP-1 complex that
      accumulates in neurites independent of nonphosphorylated APP.

PMID- 16301331
TI  - Androgen-dependent apoptosis in male germ cells is regulated through the proto
      oncoprotein Cbl.
AB  - The proto-oncoprotein Cbl is known to control several signaling processes. It is
      highly expressed in the testis, and because spermatogenesis is androgen
      dependent, we investigated the androgen dependency expression of Cbl through its
      testicular sub-localization and its expression levels in rats that were exposed
      to the antiandrogen flutamide or were hypophysectomized. We report the androgen
      dependency of Cbl as it localizes in pachytene spermatocytes during androgen
      dependent stages, is down-regulated upon flutamide exposure, and is up-regulated
      with testosterone in hypophysectomized rats. Coculture experiments showed the key
      control exerted by the Sertoli cell on Cbl activity. As flutamide induces germ
      cell apoptosis, we investigate members of the Bcl-2 family upon flutamide
      exposure. We show that the proapoptotic Bcl-2 family member Bim mirrored Cbl
      expression through a posttranscriptional process. We also show that in Cbl
      knockout mouse testes, the imbalance between the high expression of Bim and
      Smac/Diablo and anti-apoptotic factors such as cellular inhibitor of apoptosis 2
      favors a survival process, which makes these mice unresponsive to androgen
      withdrawal and could explain their hypofertility.

PMID- 16301332
TI  - Pleiotropic effects of FGFR1 on cell proliferation, survival, and migration in a
      3D mammary epithelial cell model.
AB  - Members of the fibroblast growth factor (FGF) family and the FGF receptors
      (FGFRs) have been implicated in mediating various aspects of mammary gland
      development and transformation. To elucidate the molecular mechanisms of FGFR1
      action in a context that mimics polarized epithelial cells, we have developed an
      in vitro three-dimensional HC11 mouse mammary epithelial cell culture model
      expressing a drug-inducible FGFR1 (iFGFR1). Using this conditional model, iFGFR1
      activation in these growth-arrested and polarized mammary acini initially led to
      reinitiation of cell proliferation, increased survival of luminal cells, and loss
      of cell polarity, resulting in the disruption of acinar structures characterized
      by the absence of an empty lumen. iFGFR1 activation also resulted in a gain of
      invasive properties and the induction of matrix metalloproteinase 3 (MMP-3),
      causing the cleavage of E-cadherin and increased expression of smooth muscle
      actin and vimentin. The addition of a pan MMP inhibitor abolished these
      phenotypes but did not prevent the effects of iFGFR1 on cell proliferation or
      survival.

PMID- 16301333
TI  - Control of lateral migration and germ cell elimination by the Drosophila
      melanogaster lipid phosphate phosphatases Wunen and Wunen 2.
AB  - In most organisms, primordial germ cells (PGCs) arise far from the region where
      somatic gonadal precursors (SGPs) are specified. Although PGCs in general
      originate as a single cluster of cells, the somatic parts of the gonad form on
      each site of the embryo. Thus, to reach the gonad, PGCs not only migrate from
      their site of origin but also split into two groups. Taking advantage of high
      resolution real-time imaging, we show that in Drosophila melanogaster PGCs are
      polarized and migrate directionally toward the SGPs, avoiding the midline.
      Unexpectedly, neither PGC attractants synthesized in the SGPs nor known midline
      repellents for axon guidance were required to sort PGCs bilaterally. Repellent
      activity provided by wunen (wun) and wunen-2 (wun-2) expressed in the central
      nervous system, however, is essential in this migration process and controls PGC
      survival. Our results suggest that expression of wun/wun-2 repellents along the
      migratory paths provides faithful control over the sorting of PGCs into two
      gonads and eliminates PGCs left in the middle of the embryo.

PMID- 16301334
TI  - Dissecting independent channel and scaffolding roles of the Drosophila transient
      receptor potential channel.
AB  - Drosophila transient receptor potential (TRP) serves dual roles as a cation
      channel and as a molecular anchor for the PDZ protein, INAD (inactivation no
      afterpotential D). Null mutations in trp cause impairment of visual transduction,
      mislocalization of INAD, and retinal degeneration. However, the impact of
      specifically altering TRP channel function is not known because existing loss-of
      function alleles greatly reduce protein expression. In the current study we
      describe the isolation of a set of new trp alleles, including trp(14) with an
      amino acid substitution juxtaposed to the TRP domain. The trp(14) flies stably
      express TRP and display normal molecular anchoring, but defective channel
      function. Elimination of the anchoring function alone in trp(Delta)(1272), had
      minor effects on retinal morphology whereas disruption of channel function caused
      profound light-induced cell death. This retinal degeneration was greatly
      suppressed by elimination of the Na(+)/Ca(2+) exchanger, CalX, indicating that
      the cell death was due primarily to deficient Ca(2+) entry rather than disruption
      of the TRP-anchoring function.

PMID- 16301335
TI  - Specific integrin alpha and beta chain phosphorylations regulate LFA-1 activation
      through affinity-dependent and -independent mechanisms.
AB  - Integrins are adhesion receptors that are crucial to the functions of
      multicellular organisms. Integrin-mediated adhesion is a complex process that
      involves both affinity regulation and cytoskeletal coupling, but the molecular
      mechanisms behind this process have remained incompletely understood. In this
      study, we report that the phosphorylation of each cytoplasmic domain of the
      leukocyte function-associated antigen-1 integrin mediates different modes of
      integrin activation. alpha Chain phosphorylation on Ser1140 is needed for
      conformational changes in the integrin after chemokine- or integrin ligand
      induced activation or after activation induced by active Rap1 (Rap1V12). In
      contrast, the beta chain Thr758 phosphorylation mediates selective binding to 14
      3-3 proteins in response to inside-out activation through the T cell receptor,
      resulting in cytoskeletal rearrangements. Thus, site-specific phosphorylation of
      the integrin cytoplasmic domains is important for the dynamic regulation of these
      complex receptors in cells.

PMID- 16301337
TI  - Block of peripheral nerve sodium channels selectively inhibits features of
      neuropathic pain in rats.
AB  - Several sodium channel blockers are used clinically to treat neuropathic pain.
      However, many patients fail to achieve adequate pain relief from these highly
      brain-penetrant drugs because of dose-limiting central nervous system side
      effects. Here, we describe the functional properties of trans-N-{[2'
      (aminosulfonyl)biphenyl-4-yl]methyl}-N-methyl-N'-[4
      (trifluoromethoxy)benzyl]cyclopentane-1,2-dicarboxamide (CDA54), a peripherally
      acting sodium channel blocker. In whole-cell electrophysiological assays, CDA54
      blocked the inactivated states of hNa(V)1.7 and hNa(V)1.8, two channels of the
      peripheral nervous system implicated in nociceptive transmission, with affinities
      of 0.25 and 0.18 microM, respectively. CDA54 displayed similar affinities for the
      tetrodotoxin-resistant Na+ current in small-diameter mouse dorsal root ganglion
      neurons. Peripheral nerve injury causes spontaneous electrical activity in
      normally silent sensory neurons. CDA54 inhibited these injury-induced spontaneous
      action potentials at concentrations 10-fold lower than those required to block
      normal A- and C-fiber conduction. Consistent with the selective inhibition of
      injury-induced firing, CDA54 (10 mg/kg p.o.) significantly reduced behavioral
      signs of neuropathic pain in two nerve injury models, whereas the same dose of
      CDA54 did not affect acute nociception or motor coordination. In anesthetized
      dogs, CDA54, at plasma concentrations of 6.7 microM, had no effect on cardiac
      electrophysiological parameters including conduction. Thus, the peripheral nerve
      sodium channel blocker CDA54 selectively inhibits sensory nerve signaling
      associated with neuropathic pain.

PMID- 16301336
TI  - Ablation of beta1 integrin in mammary epithelium reveals a key role for integrin
      in glandular morphogenesis and differentiation.
AB  - Integrin-mediated adhesion regulates the development and function of a range of
      tissues; however, little is known about its role in glandular epithelium. To
      assess the contribution of beta1 integrin, we conditionally deleted its gene in
      luminal epithelia during different stages of mouse mammary gland development and
      in cultured primary mammary epithelia. Loss of beta1 integrin in vivo resulted in
      impaired alveologenesis and lactation. Cultured beta1 integrin-null cells
      displayed abnormal focal adhesion function and signal transduction and could not
      form or maintain polarized acini. In vivo, epithelial cells became detached from
      the extracellular matrix but remained associated with each other and did not
      undergo overt apoptosis. beta1 integrin-null mammary epithelial cells did not
      differentiate in response to prolactin stimulation because of defective Stat5
      activation. In mice where beta1 integrin was deleted after the initiation of
      differentiation, fewer defects in alveolar morphology occurred, yet major
      deficiencies were also observed in milk protein and milk fat production and Stat5
      activation, indicating a permissive role for beta1 integrins in prolactin
      signaling. This study demonstrates that beta1 integrin is critical for the
      alveolar morphogenesis of a glandular epithelium and for maintenance of its
      differentiated function. Moreover, it provides genetic evidence for the
      cooperation between integrin and cytokine signaling pathways.

PMID- 16301338
TI  - Vasorelaxation in space.
AB  - During everyday life, gravity constantly stresses the cardiovascular system in
      upright humans by diminishing venous return. This decreases cardiac output and
      induces systemic vasoconstriction to prevent blood pressure from falling. We
      therefore tested the hypothesis that entering weightlessness leads to a prompt
      increase in cardiac output and to systemic vasodilatation and that these effects
      persist for at least a week of weightlessness in space. Cardiac output and mean
      arterial pressure were measured in 8 healthy humans during acute 20-s periods of
      weightlessness in parabolic airplane flights and on the seventh and eighth day of
      weightlessness in 4 astronauts in space. The seated 1-G position acted as
      reference. Entering weightlessness promptly increased cardiac output by 29+/-7%,
      from 6.6+/-0.7 to 8.4+/-0.9 L min(-1) (mean+/-SEM; P=0.003), whereas mean
      arterial pressure and heart rate were unaffected. Thus, systemic vascular
      resistance decreased by 24+/-4% (P=0.017). After a week of weightlessness in
      space, cardiac output was increased by 22+/-8% from 5.1+/-0.3 to 6.1+/-0.1 L min(
      1) (P=0.021), with mean arterial pressure and heart rate being unchanged so that
      systemic vascular resistance was decreased by 14+/-9% (P=0.047). In conclusion,
      entering weightlessness promptly increases cardiac output and dilates the
      systemic circulation. This vasorelaxation persists for at least a week into
      spaceflight. Thus, it is probably healthy for the human cardiovascular system to
      fly in space.

PMID- 16301339
TI  - Prothrombotic mutations, hormone therapy, and venous thromboembolism among
      postmenopausal women: impact of the route of estrogen administration.
AB  - BACKGROUND: Oral estrogen increases the risk of venous thromboembolism (VTE) in
      postmenopausal women, particularly in those with a prothrombotic mutation.
      Transdermal estrogen may be safe with respect to VTE. We investigated the impact
      of the route of estrogen administration on the association between a
      prothrombotic mutation (factor V Leiden or prothrombin G20210A mutation) and VTE
      risk. METHODS AND RESULTS: We performed a multicenter case-control study of VTE
      among postmenopausal women who were enrolled in 1999 through 2004 at 7 clinical
      centers in France. We recruited 235 consecutive patients with a first documented
      episode of idiopathic VTE and 554 controls. Factor V Leiden was associated with a
      3.4-fold-increased risk of VTE (95% confidence interval [CI], 2.0 to 5.8), and a
      prothrombin mutation was associated with a 4.8-fold-increased risk of VTE (95%
      CI, 2.5 to 9.4). Oral but not transdermal estrogen was associated with an
      increased risk of VTE (odds ratio [OR], 4.3; 95% CI, 2.6 to 7.2; and OR, 1.2; 95%
      CI, 0.8 to 1.7, respectively). After adjustment for potential confounding
      factors, the combination of either factor V Leiden or prothrombin G20210A
      mutation and oral estrogen gave a 25-fold-increased risk of VTE compared with
      nonusers without mutation (95% CI, 6.9 to 95.0). However, the risk for women with
      prothrombotic mutation using transdermal estrogen was similar to that of women
      with a mutation who were not using estrogen (OR, 4.4; 95% CI, 2.0 to 9.9; and OR,
      4.1; 95% CI, 2.3 to 7.4, respectively). CONCLUSIONS: In contrast to oral
      estrogen, transdermal estrogen does not confer additional risk on women who carry
      a prothrombotic mutation. The safety of transdermal estrogen has to be confirmed
      in randomized trials.

PMID- 16301340
TI  - Effect of thalidomide on cardiac remodeling in chronic heart failure: results of
      a double-blind, placebo-controlled study.
AB  - BACKGROUND: Inflammation and matrix degradation may play a pathogenic role in
      chronic heart failure (CHF), and therefore, we examined whether thalidomide, a
      drug with potential immunomodulating and matrix-stabilizing properties, could
      improve left ventricular (LV) function in patients with CHF secondary to
      idiopathic dilated cardiomyopathy (IDCM) or coronary artery disease (CAD).
      METHODS AND RESULTS: Fifty-six patients with CHF and an LV ejection fraction
      (LVEF) <40% who were already on optimal conventional cardiovascular treatment
      were randomized to thalidomide (25 mg QD increasing to 200 mg QD) or placebo and
      followed up for 12 weeks. Our main findings were as follows: (1) During
      thalidomide treatment but not during placebo, there was a marked increase in LVEF
      (&7 EF units) along with a significant decrease in LV end-diastolic volume and
      heart rate. (2) This improvement in LVEF was accompanied by a decrease in matrix
      metalloproteinase-2 without any changes in its endogenous tissue inhibitor,
      suggesting a matrix-stabilizing net effect. (3) Thalidomide also induced a
      decrease in total neutrophil count and an increase in plasma levels of tumor
      necrosis factor-alpha, suggesting both proinflammatory and antiinflammatory
      effects. (4) The effect of thalidomide on LVEF was more marked in IDCM than in
      CAD, possibly partly reflecting that the former group was able to tolerate a
      higher thalidomide dosage. CONCLUSIONS: Although our results must be confirmed in
      larger studies that also examine the effects on morbidity and mortality, our
      findings suggest a role for thalidomide in the management of CHF in addition to
      traditional cardiovascular medications.

PMID- 16301341
TI  - Deficiency of neuronal nitric oxide synthase increases mortality and cardiac
      remodeling after myocardial infarction: role of nitroso-redox equilibrium.
AB  - BACKGROUND: Neuronal nitric oxide synthase (NOS1) plays key cardiac physiological
      roles, regulating excitation-contraction coupling and exerting an antioxidant
      effect that maintains tissue NO-redox equilibrium. After myocardial infarction
      (MI), NOS1 translocates from the sarcoplasmic reticulum to the cell membrane,
      where it inhibits beta-adrenergic contractility, an effect previously predicted
      to have adverse consequences. Counter to this idea, we tested the hypothesis that
      NOS1 has a protective effect after MI. METHODS AND RESULTS: We studied mortality,
      cardiac remodeling, and upregulation of oxidative stress pathways after MI in
      NOS1-deficient (NOS1(-/-)) and wild-type C57BL6 (WT) mice. Compared with WT,
      NOS1(-/-) mice had greater mortality (hazard ratio, 2.06; P=0.036), worse left
      ventricular (LV) fractional shortening (19.7+/-1.5% versus 27.2+/-1.5%, P<0.05),
      higher LV diastolic diameter (5.5+/-0.2 versus 4.9+/-0.1 mm, P<0.05), greater
      residual cellular width (14.9+/-0.5 versus 12.8+/-0.5 microm, P<0.01), and
      equivalent beta-adrenergic hyporesponsiveness despite similar MI size. Superoxide
      production increased after MI in both NOS1(-/-) and WT animals, although NO
      increased only in WT. NADPH oxidase (P<0.05) activity increased transiently in
      both groups after MI, but NOS1(-/-) mice had persistent basal and post-MI
      elevations in xanthine oxidoreductase activity. CONCLUSIONS: Together these
      findings support a protective role for intact NOS1 activity in the heart after
      MI, despite a potential contribution to LV dysfunction through beta-adrenergic
      hyporesponsiveness. NOS1 deficiency contributes to an imbalance between oxidative
      stress and tissue NO signaling, providing a plausible mechanism for adverse
      consequences of NOS1 deficiency in states of myocardial injury.

PMID- 16301342
TI  - Association of WNK1 gene polymorphisms and haplotypes with ambulatory blood
      pressure in the general population.
AB  - BACKGROUND: Blood pressure (BP) is a heritable trait of major public health
      concern. The WNK1 and WNK4 genes, which encode proteins in the WNK family of
      serine-threonine kinases, are involved in renal electrolyte homeostasis.
      Mutations in the WNK1 and WNK4 genes cause a rare monogenic hypertensive
      syndrome, pseudohypoaldosteronism type II. We investigated whether polymorphisms
      in these WNK genes influence BP in the general population. METHODS AND RESULTS:
      Associations between 9 single-nucleotide polymorphisms (SNPs) in WNK1 and 1 in
      WNK4 with ambulatory BP were studied in a population-based sample of 996 subjects
      from 250 white European families. The heritability estimates of mean 24-hour
      systolic BP (SBP) and diastolic BP (DBP) were 63.4% and 67.9%, respectively. We
      found statistically significant (P<0.05) associations of several common SNPs and
      haplotypes in WNK1 with mean 24-hour SBP and/or DBP. The minor allele (C) of
      rs880054, with a frequency of 44%, reduced mean 24-hour SBP and DBP by 1.37 (95%
      confidence interval, -2.45 to -0.23) and 1.14 (95% confidence interval, -1.93 to 
      0.38) mm Hg, respectively, per copy of the allele. CONCLUSIONS: Common variants
      in WNK1 contribute to BP variation in the general population. This study shows
      that a gene causing a rare monogenic form of hypertension also plays a
      significant role in BP regulation in the general population. The findings provide
      a basis to identify functional variants of WNK1, elucidate any interactions of
      these variants with dietary intake or with response to antihypertensive drugs,
      and determine their impact on cardiovascular morbidity and mortality.

PMID- 16301343
TI  - Mortality and morbidity remain high despite captopril and/or Valsartan therapy in
      elderly patients with left ventricular systolic dysfunction, heart failure, or
      both after acute myocardial infarction: results from the Valsartan in Acute
      Myocardial Infarction Trial (VALIANT).
AB  - BACKGROUND: The elderly constitute an increasing proportion of acute myocardial
      infarction patients and have disproportionately high mortality and morbidity.
      Those with heart failure or impaired left ventricular left ventricular function
      after acute myocardial infarction have high complication and mortality rates.
      Little is known about outcomes with contemporary therapies in these patients.
      METHODS AND RESULTS: The Valsartan in Acute Myocardial Infarction Trial (VALIANT)
      randomized 14,703 patients with heart failure and/or left ventricular ejection
      fraction <40% to receive captopril, valsartan, or both. Mortality and a composite
      end point, including cardiovascular mortality, readmission for heart failure,
      reinfarction, stroke, and resuscitated cardiac arrest, were compared for the age
      groups of <65 (n=6988), 65 to 74 (n=4555), 75 to 84 (n=2777), and > or =85
      (n=383) years. With increasing age, 3-year mortality almost quadrupled (13.4%,
      26.3%, 36.0%, and 52.1%, respectively), composite end-point events more than
      doubled (25.2%, 41.0%, 52.3%, and 66.8%), and hospital admissions for heart
      failure almost tripled (12.0%, 23.1%, 31.3%, and 35.4%). Outcomes did not differ
      between the 3 study treatments in any age group. Adverse events associated with
      captopril and valsartan were more common in the elderly and in patients receiving
      combination therapy. With increasing age, use of aspirin, beta-blockers, and
      statins declined, and use of digoxin, calcium-channel blockers, and non-potassium
      sparing diuretics increased. On 3-year multivariable analysis, each 10-year age
      increase was associated with a hazard ratio of 1.49 (95% CI, 1.426 to 1.557;
      P<0.0001) for mortality and an odds ratio of 1.38 (95% CI, 1.31 to 1.46;
      P<0.0001) for readmission with heart failure. CONCLUSIONS: Outcomes remained poor
      in elderly patients with heart failure and/or impaired left ventricular systolic
      function after acute myocardial infarction, although most received beta-blockers
      and all received an ACE inhibitor and/or an angiotensin receptor blocker. Better
      therapies and increased use of aspirin, beta-blockers, and statins are needed in
      this important and increasing patient group.

PMID- 16301344
TI  - Risk of high blood pressure among young men increases with the degree of
      immaturity at birth.
AB  - BACKGROUND: Survivors of preterm birth constitute a new generation of young
      adults, but little is known about their long-term health. We investigated the
      association between gestational age (GA) and risk of high blood pressure (HBP) in
      young Swedish men and whether GA modified the risk of HBP; ie, whether HBP was
      related to being born small for gestational age (SGA). METHODS AND RESULTS: This
      population-based cohort study included 329 495 Swedish men born in 1973 to 1981
      who were conscripted for military service in 1993 to 2001. Multivariate linear-
      and logistic-regression analyses were performed. Main outcome measures were
      systolic and diastolic BPs at conscription. Linear-regression analyses showed
      that systolic BP increased with decreasing GA (regression coefficient -0.31 mm
      Hg/wk, P<0.001). Systolic and diastolic BPs both increased with decreasing birth
      weight for GA, but the association with systolic BP was most evident (regression
      coefficient -0.67 mm Hg per SD score in birth weight for GA, P<0.001). Compared
      with men born at term (GA, 37 to 41 weeks), the adjusted odd ratios (95%
      confidence intervals [CIs]) for high systolic BP (> or =140 mm Hg) were as
      follows: moderately preterm (33 to 36 weeks), 1.25 (1.19 to 1.30); very preterm
      (29 to 32 weeks), 1.48 (1.30 to 1.68); and extremely preterm (24 to 28 weeks),
      1.93 (1.34 to 2.76). Being SGA was associated only with an increased risk of high
      systolic BP among men born at 33 weeks or later. The risk estimates for high
      diastolic BP (> or =90 mm Hg) increased with decreasing GA, but the risk reached
      significance only among men born moderately preterm. CONCLUSIONS: Preterm birth,
      a common pregnancy complication, is a risk factor for HBP in young men. The risk
      of high systolic BP associated with birth weight for GA is modified by GA,
      suggesting that perinatal contributions to BP elevation later in life may be
      induced by different biological pathways.

PMID- 16301345
TI  - Joint effects of systolic blood pressure and serum cholesterol on cardiovascular
      disease in the Asia Pacific region.
AB  - BACKGROUND: Although interest in multifactorial interventions for cardiovascular
      disease is increasing, data on the strength and shape of the joint effects of
      blood pressure and cholesterol levels on the risk of cardiovascular disease are
      scarce, confined primarily to coronary heart disease (CHD) mortality in early
      middle-aged Western populations. METHODS AND RESULTS: This analysis included 29
      cohorts from Asia (78% of the total 380,216 participants) and 7 from Australia
      and New Zealand, with a total of 2,547,447 person-years of observation.
      Stratified time-dependent Cox proportional-hazards analyses were used to regress
      time until first event against baseline systolic blood pressure (SBP) and total
      cholesterol levels. A total of 3079 CHD and 4247 stroke events occurred; stroke
      subtypes were confirmed by CT, MRI, or necropsy in 1471 (35%) stroke events.
      Usual values of SBP were strongly linearly associated with ischemic stroke,
      hemorrhagic stroke, and CHD. The slope of the association with SBP became steeper
      with decreasing levels of cholesterol for ischemic stroke (P=0.007) and CHD (P<
      or =0.0001). For example, for the cholesterol groups of <4.75, 4.75 to 5.49, 5.50
      to 6.24, and > or =6.25 mmol/L, each 10-mm Hg-higher systolic pressure was
      associated with 34% (95% CI, 30% to 37%), 28% (95% CI, 21% to 35%), 25% (95% CI,
      18% to 32%), and 21% (95% CI, 13% to 27%) higher CHD risk, respectively.
      Adjustments for other leading cardiovascular risk factors made no appreciable
      differences in these results. CONCLUSIONS: In Asia-Pacific populations, there are
      hazards of increasing SBP at all cholesterol levels and hazards of increasing
      cholesterol at all levels of SBP, but the associations of SBP with CHD risk and
      ischemic stroke risk are slightly steeper among those with low cholesterol
      levels. The joint effects of SBP and total cholesterol on cardiovascular disease
      seem consistent across various Western and Asian populations.

PMID- 16301346
TI  - In vivo quantitative measurement of intact fibrous cap and lipid-rich necrotic
      core size in atherosclerotic carotid plaque: comparison of high-resolution,
      contrast-enhanced magnetic resonance imaging and histology.
AB  - BACKGROUND: Previous studies with contrast-enhanced magnetic resonance imaging
      (CEMRI) have shown that the fibrous cap (FC) in atherosclerotic carotid plaques
      enhances with gadolinium-based contrast agents. Conversely, the lipid-rich
      necrotic core (LR-NC), lacking both vasculature and matrix, shows no or only
      slight enhancement. The goal of this study was to assess whether CEMRI can be
      used to accurately measure the dimensions of the intact FC and LR-NC. METHODS AND
      RESULTS: Twenty-one patients scheduled for carotid endarterectomy were imaged
      with a 1.5-T scanner. Precontrast images and CEMRI were obtained. One hundred
      eight locations with an intact FC were matched between MRI and the excised
      histology specimens. Quantitative measurements of FC length along the lumen
      circumference, FC area, and LR-NC area were collected from CEMRI images and
      histology sections. Blinded comparison of corresponding MR images and histology
      slices showed moderate to good correlation for length (r=0.73, P<0.001) and area
      (r=0.80, P<0.001) of the intact FC. The mean percentage LR-NC areas (LR-NC
      area/wall area) measured by CEMRI and histology were 30.1% and 32.7%,
      respectively, and were strongly correlated across locations (r=0.87, P<0.001).
      CONCLUSIONS: In vivo high-resolution CEMRI is capable of quantitatively measuring
      the dimensions of the intact FC and LR-NC. These new parameters may be useful to
      evaluate plaque vulnerability and provide continuous variables for characterizing
      the intact FC and LR-NC in progression and regression studies.

PMID- 16301347
TI  - Images in cardiovascular medicine. Unusual case of pheochromocytoma with a
      surprising response to the intravenous administration of norepinephrine.

PMID- 16301348
TI  - Images in cardiovascular medicine. Cardiac metastasis: visualization with
      positron emission tomography, computed tomography, magnetic resonance imaging,
      positron emission tomography/computed tomography, and positron emission
      tomography/magnetic resonance imaging.

PMID- 16301349
TI  - Images in cardiovascular medicine. Serial changes of the electrocardiogram during
      the progression of subarachnoidal hemorrhage.

PMID- 16301350
TI  - Letter regarding article by Koch et al, "Impact of prothesis-patient size on
      functional recovery after aortic valve replacement".

PMID- 16301351
TI  - Oral anticoagulation for atrial fibrillation after ST-elevation myocardial
      infarction: new evidence to guide clinical practice.

PMID- 16301352
TI  - Biomarkers of ischemia in patients with known coronary artery disease: do
      interleukin-6 and tissue factor measurements during dobutamine stress
      echocardiography give additional insight?

PMID- 16301353
TI  - Modulation of myocardial energetics: emerging evidence for a therapeutic target
      in cardiovascular disease.

PMID- 16301354
TI  - Resting blood flow in hypocontractile myocardium: resolving the controversy.

PMID- 16301355
TI  - Anticoagulation therapy in atrial fibrillation in combination with acute
      myocardial infarction influences long-term outcome: a prospective cohort study
      from the Register of Information and Knowledge About Swedish Heart Intensive Care
      Admissions (RIKS-HIA).
AB  - BACKGROUND: The American and European guidelines do not agree with regard to
      antithrombotic treatment in patients with atrial fibrillation (AF) and acute
      myocardial infarction (AMI), thus causing uncertainty among physicians. We
      investigated the prescription of oral anticoagulation (OAC) in patients
      discharged alive with AF after an AMI and the influence of OAC treatment on 1
      year mortality. METHODS AND RESULTS: This was a prospective cohort study using
      data from the Register of Information and Knowledge about Swedish Heart Intensive
      care Admissions (RIKS-HIA) on patients admitted to the coronary care units of 72
      Swedish hospitals from 1995 to 2002. A total of 6182 patients discharged alive
      with first registry-recorded AMI and AF on discharge ECG were included. One-year
      mortality data were obtained from the Swedish National Cause of Death Register.
      Only 30% (n=1848) of the 6182 patients with AF were prescribed OAC. At 1 year,
      the unadjusted mortality was 31% (1183 deaths) in the platelet-inhibitors only
      group and 22% (414 deaths) in the OAC-treated group. In Cox regression analysis
      with adjustment for confounding factors, OAC treatment was associated with a
      reduction in 1-year mortality (relative risk 0.73; 95% CI 0.62 to 0.86; P<0.001)
      in hospital survivors of AMI with AF. The reduction in mortality appeared to be
      caused primarily by a lower rate of ischemic heart death (55.6% versus 62.0%) and
      fatal stroke (5.7% versus 7.5%) in the OAC group. This reduction of mortality was
      similar among most subgroups based on age, sex, baseline characteristics,
      previous disease manifestations, and medications. CONCLUSIONS: In daily clinical
      practice, OAC was only given to a minority (30%) of AMI patients with AF, despite
      the fact that OAC was associated with a 29% relative and 7% absolute reduction in
      1-year mortality after adjustment for confounding variables. The results
      emphasize the importance of OAC treatment for AF after AMI.

PMID- 16301356
TI  - Dietary alpha-linolenic acid intake and risk of sudden cardiac death and coronary
      heart disease.
AB  - BACKGROUND: Alpha-linolenic acid, an intermediate-chain n-3 fatty acid found
      primarily in plants, may decrease the risk of fatal coronary heart disease (CHD)
      through a reduction in fatal ventricular arrhythmias and sudden cardiac death
      (SCD). METHODS AND RESULTS: We prospectively examined the association between
      dietary intake of alpha-linolenic acid assessed via updated food-frequency
      questionnaires and the risk of SCD, other fatal CHD, and nonfatal myocardial
      infarction (MI) among 76,763 women participating in the Nurses' Health Study who
      were free from cancer and completed a dietary questionnaire at baseline in 1984.
      During 18 years of follow-up, we identified 206 SCDs, 641 other CHD deaths, and
      1604 nonfatal MIs. After controlling for coronary risk factors and other fatty
      acids, including long-chain n-3 fatty acids, the intake of alpha-linolenic acid
      was inversely associated with the risk of SCD (P for trend, 0.02) but not with
      the risk of other fatal CHD or nonfatal MI. Compared with women in the lowest
      quintile of alpha-linolenic acid intake, those in the highest 2 quintiles had a
      38% to 40% lower SCD risk. This inverse relation with SCD risk was linear and
      remained significant even among women with high intakes of long-chain n-3 fatty
      acids. CONCLUSIONS: These prospective data suggest that increasing dietary intake
      of alpha-linolenic acid may reduce the risk of SCD but not other types of fatal
      CHD or nonfatal MI in women. The specificity of the association between alpha
      linolenic acid and SCD supports the hypothesis that these n-3 fatty acids may
      have antiarrhythmic properties.

PMID- 16301357
TI  - New mechanism contributing to drug-induced arrhythmia: rescue of a misprocessed
      LQT3 mutant.
AB  - BACKGROUND: The cardiac sodium channel (SCN5A) mutation L1825P has been
      identified in a patient with drug-induced torsade de pointes precipitated by the
      IKr blocker cisapride. Although L1825P generates late sodium current typical of
      SCN5A-linked long-QT syndrome (LQT3) in vitro, the patient reported had a normal
      QT interval before administration of the drug. To address this discrepancy, we
      tested the hypothesis that this mutant channel is not processed normally. METHODS
      AND RESULTS: CHO cells transfected with L1825P displayed significantly reduced
      peak INa (209+/-36 versus 23+/-3 pA/pF, P<0.05). Confocal imaging and cell
      counting studies using epitope-tagged constructs demonstrated that cell surface
      expression of the mutant was only approximately 9% of wild-type. Incubating
      transfected cells with cisapride partially rescued misprocessing to 30% of wild
      type. As a result, "late" sodium current increased with cisapride from 1.2+/-0.11
      to 5.04+/-0.77 pA/pF (P<0.05). CONCLUSIONS: L1825P fails to generate QT
      prolongation because it does not reach the cell surface. Moreover, the data
      suggest that cisapride caused torsade de pointes not only by blocking IKr but
      also by rescuing cell surface expression of the mutant channel, further
      exaggerating the LQT3 phenotype. This not only represents a new mechanism in the
      drug-induced long-QT syndrome but also strongly supports the concept that
      variable cell surface expression contributes to clinical variability in the LQT3
      phenotype.

PMID- 16301358
TI  - Cardiac magnetic resonance imaging after stage I Norwood operation for
      hypoplastic left heart syndrome.
AB  - BACKGROUND: After the Norwood operation, a patient's suitability for proceeding
      to a bidirectional cavopulmonary connection (BCPC) is assessed by a combination
      of echocardiography and diagnostic cardiac catheterization. In this study, we
      describe the results of 37 patients who underwent cardiovascular magnetic
      resonance (MR) assessment before BCPC. METHODS AND RESULTS: Cardiovascular MR and
      echocardiography were performed in 37 infants with hypoplastic left heart
      syndrome before BCPC, and the findings were compared with surgical findings. MR
      assessment of ventricular function and valvar regurgitation were compared with
      echocardiography. MR exhibited high sensitivity and specificity for
      identification of neoaortic (sensitivity 86%, specificity 97%) and left pulmonary
      artery (sensitivity 100%, specificity 94%) obstruction. Echocardiography
      exhibited poor sensitivity for identification of vascular stenosis. The mean
      right ventricular ejection fraction calculated from the MR data was 50+/-10%.
      There was general agreement between MR and echocardiographic measures of
      ventricular function, although patients with good function on echocardiography
      demonstrated a wide range of ejection fractions. There was good agreement between
      MR and echocardiography for identification of valvar regurgitation. CONCLUSIONS:
      Cardiovascular MR can be used to define ventricular and valvar function and
      vascular anatomy in infants with hypoplastic left heart syndrome after the
      Norwood operation. We have shown how this information can be used to plan the
      BCPC and identify any revisions or additional valvar surgery.

PMID- 16301359
TI  - Metabolic modulation with perhexiline in chronic heart failure: a randomized,
      controlled trial of short-term use of a novel treatment.
AB  - BACKGROUND: Chronic heart failure (CHF) is a major cause of morbidity and
      mortality that requires a novel approach to therapy. Perhexiline is an
      antianginal drug that augments glucose metabolism by blocking muscle
      mitochondrial free fatty acid uptake, thereby increasing metabolic efficiency. We
      assessed the effects of perhexiline treatment in CHF patients. METHODS AND
      RESULTS: In a double-blind fashion, we randomly assigned patients with optimally
      medicated CHF to either perhexiline (n=28) or placebo (n=28). The primary end
      point was peak exercise oxygen consumption (VO2max), an important prognostic
      marker. In addition, the effect of perhexiline on myocardial function and quality
      of life was assessed. Quantitative stress echocardiography with tissue Doppler
      measurements was used to assess regional myocardial function in patients with
      ischemic CHF. 31P magnetic resonance spectroscopy was used to assess the effect
      of perhexiline on skeletal muscle energetics in patients with nonischemic CHF.
      Treatment with perhexiline led to significant improvements in VO2max (16.1+/-0.6
      to 18.8+/-1.1 mL . kg(-1) . min(-1); P<0.001), quality of life (Minnesota score
      reduction from 45+/-5 to 34+/-5; P=0.04), and left ventricular ejection fraction
      (24+/-1% to 34+/-2%; P<0.001). Perhexiline treatment also increased resting and
      peak dobutamine stress regional myocardial function (by 15% and 24%,
      respectively) and normalized skeletal muscle phosphocreatine recovery after
      exercise. There were no adverse effects during the treatment period. CONCLUSIONS:
      In patients with CHF, metabolic modulation with perhexiline improved VO2max, left
      ventricular ejection fraction, symptoms, resting and peak stress myocardial
      function, and skeletal muscle energetics. Perhexiline may therefore represent a
      novel treatment for CHF with a good safety profile, provided that the dosage is
      adjusted according to plasma levels.

PMID- 16301360
TI  - Accelerated atherosclerosis in autoimmune rheumatic diseases.

PMID- 16301361
TI  - Atherosclerosis 2005: recent discoveries and novel hypotheses.

PMID- 16301362
TI  - Medical director responsibilities for outpatient cardiac rehabilitation/secondary
      prevention programs: a scientific statement from the American Heart
      Association/American Association for Cardiovascular and Pulmonary Rehabilitation.

PMID- 16301363
TI  - Our approach to addressing potential conflicts of interest.

PMID- 16301364
TI  - Quantitative detection of substitute voice generator during phonation in patients
      undergoing laryngectomy.
AB  - OBJECTIVE: To evaluate the vibration pattern of the substitute voice generator of
      patients who have undergone laryngectomy. For automatic quantification of the
      oscillations of the pharyngoesophageal (PE) segments, image processing of digital
      high-speed video sequences is applied. DESIGN: Physiologic analysis. SETTING: An
      acute care hospital. PATIENTS: Endoscopic recordings were taken of 10 men who
      underwent laryngectomy (mean +/- SD age, 61.5 +/- 5.2 years) during sustained
      phonation of a vowel using a 90 degree endoscope coupled to a high-speed camera.
      MAIN OUTCOME MEASURES: An image-processing algorithm was developed to
      automatically define the pseudoglottis in each recording and track its movements.
      RESULTS: The clinical assessment of the high-speed technique for the endoscopic
      examination of the substitute voice generator yields the following results. The
      forms and oscillation characteristics of the pseudoglottides varied considerably:
      3 pseudoglottides were circular, 6 were split shaped, and 1 was triangle shaped.
      A quasi-periodic opening and closing were observed and automatically detected by
      the described algorithm in each recording independently from quality of the
      recording and from morphologic and oscillation characteristics of the PE segment.
      The frequencies of the extracted oscillations of the pseudoglottides correspond
      to the structure of the acoustic signals. CONCLUSIONS: Automatic image processing
      of PE segments derived from high-speed endoscopic recordings enables the
      detection and quantification of the substitute voice generator's oscillations in
      high temporal resolution. These data directly prove that the detected
      pseudoglottis is the source of the substitute voice. Close relations between
      substitute voice and functional properties of the PE segment exist. In the
      future, these data will be interpreted by applying biomechanical models of the PE
      segment. Presumably, results may help to optimize surgical and adaptive
      procedures for specific substitute voice restoration.

PMID- 16301365
TI  - Long-term performance of indwelling tracheoesophageal speaking valves in Chinese
      patients undergoing laryngectomy.
AB  - OBJECTIVES: To assess the use of indwelling tracheoesophageal speaking valves in
      Chinese patients undergoing laryngectomy, to identify the clinicopathologic
      factors for favorable outcome, and to evaluate the factors that determine
      prosthesis lifetime. DESIGN: Retrospective review. SETTING: Tertiary care
      institution. PATIENTS: Sixty consecutive patients with total laryngectomy were
      included. All had indwelling tracheoesophageal speaking valves for voice
      restoration. INTERVENTION: Anterograde replacement of voice prosthesis in case of
      failure of functional speech production or leakage of saliva. MAIN OUTCOME
      MEASURES: Incidence of successful tracheoesophageal speech rehabilitation for
      daily communication, influence of different clinicopathologic factors on the
      outcome, and prosthesis lifetime and its relationship to different
      clinicopathologic factors. RESULTS: The success rate of speech rehabilitation was
      78%. Age younger than 60 years was the only clinicopathologic factor associated
      with successful speech rehabilitation (P = .04, Fisher exact test). The median
      device lifetime was 8.2 months. Both age of 60 years or older and the use of
      subsequent prosthetic valves were identified as risk factors for valve failure on
      univariate analysis (n = 192; log-rank test; P = .02 and P = .03, respectively),
      with age of 60 years or older as the only risk factor that reduced the device
      lifetime in the Cox proportional hazards model (P = .03; relative hazard ratio,
      1.5; 95% confidence interval, 1.1-2.4). CONCLUSIONS: Our success rate in using
      indwelling tracheoesophageal speaking valves was comparable to that reported in
      the Western literature. The median device lifetime of 8.2 months was
      satisfactory. Patient age was found to be a significant predictor of successful
      tracheoesophageal speech rehabilitation, with age of 60 years or more adversely
      affecting device lifetime.

PMID- 16301366
TI  - Validity and reliability of the glottal function index.
AB  - OBJECTIVE: To evaluate a symptom-focused vocal impairment instrument for the
      evaluation of patients with voice disorders. DESIGN: Prospective, nonrandomized
      study of patients with voice disorders undergoing treatment with validation of a
      new symptom index, the Glottal Function Index (GFI). SETTING: Voice disorders
      clinic at an academic tertiary care hospital. PATIENTS: Consecutive patients
      undergoing therapy for glottal insufficiency, adductor spasmodic dysphonia,
      nodules, and granuloma (40 patients in each group) and 40 control patients.
      INTERVENTIONS: The Pearson correlation coefficient was used to evaluate GFI
      reproducibility and to compare it with the Voice Handicap Index (VHI). The paired
      samples t test was used to compare pretherapy and posttherapy GFI values. MAIN
      OUTCOME MEASURES: Correlation of GFI with VHI; comparison of the GFI in normals,
      and in pretherapy and posttherapy GFI and VHI scores. RESULTS: The mean +/- SD
      normative GFI score was 0.87 +/- 1.32. The correlation coefficient for GFI
      between independent pretherapy measurements was 0.56 (P<.001). The correlation
      coefficient between total GFI and total VHI scores was 0.61 (P<.001). The mean
      posttherapy GFI scores improved among all groups as follows: glottal
      insufficiency: presenting GFI score, 12.7 +/- 4.1; posttherapy GFI score, 6.8 +/-
      5.4; nodules: presenting GFI score, 12.9 +/- 4.2; posttherapy GFI score, 8.9 +/-
      4.6; adductor spasmodic dysphonia: presenting GFI score, 13.2 +/- 4.1;
      posttherapy GFI score, 8.9 +/- 4.9; and granuloma: presenting GFI score, 7.8 +/-
      4.6; posttherapy GFI score, 3.8 +/- 2.1. Relative to controls, the GFI score at
      presentation was significantly elevated and demonstrated significant reduction
      following treatment across each of these entities (P<.05). CONCLUSIONS: The GFI
      is a reliable, reproducible, 4-item, self-administered symptom index with
      excellent criterion-based and construct validity. Its advantages over existing
      indexes include brevity and ease of administration. The GFI is a useful adjunct
      in the evaluation and treatment of patients with glottal dysfunction.

PMID- 16301367
TI  - Effectiveness of superselective and selective neck dissection for advanced nodal
      metastases after chemoradiation.
AB  - OBJECTIVE: To determine the efficacy of selective and superselective neck
      dissection for patients with bulky or residual nodal metastasis treated with
      concomitant intra-arterial cisplatin and radiotherapy. DESIGN: Prospective study.
      SETTING: University of Tennessee, Memphis. PATIENTS: A total of 240 patients with
      stage III or IV head and neck squamous cell carcinoma. INTERVENTIONS: Treatment
      with cisplatin, 150 mg/m2 intra-arterially, and sodium thiosulfate, 9 g/m2
      intravenously, weekly for 4 weeks; and radiotherapy, 2 Gy per fraction per day, 5
      times weekly, for a total of 68 to 74 Gy over 6 to 7 weeks. MAIN OUTCOME
      MEASURES: Regional control, distant metastases, and overall survival for patients
      undergoing radical or modified radical neck dissection (n = 12), selective neck
      dissection (n = 65), and superselective neck dissection (levels II-III only) (n =
      7). RESULTS: Among the total group of 240 patients, 106 neck dissections were
      performed on 84 patients who had bulky nodal disease. With a median follow-up of
      58 months (range, 12-96 months), regional failure occurred in 11 (4.6%) of 240
      patients: 2 (17%) of the 12 who had modified radical neck dissection, 3 (5%) of
      the 65 who had selective neck dissection, none of the 7 patients who had
      superselective neck dissection, and 6 (4%) of the 156 who had no neck dissection.
      The rates of overall survival and distant metastases were not significantly
      different among the 3 neck dissection subsets. CONCLUSION: Selective and
      superselective neck dissection, which spare function and minimize morbidity, are
      viable therapeutic alternatives for patients with residual disease confined to 1
      level after intra-arterial chemoradiation treatment, and possibly for other
      chemoradiation protocols.

PMID- 16301368
TI  - Pill swallowing by adults with dysphagia.
AB  - OBJECTIVE: To evaluate differences in swallowing physiology and safety in
      patients with dysphagia between conventional tablets and a new method of tablet
      transportation, orally disintegrating technology (ODT) (RapiTab; Schwarz Pharma
      Inc, Milwaukee, Wis). DESIGN: The study observed a single group, crossover
      design. SETTING: Outpatient clinic within an academic teaching hospital.
      PARTICIPANTS: A total of 36 adult dysphagic patients referred to the clinic.
      INTERVENTIONS: All subjects underwent simultaneous nasopharyngeal endoscopic
      evaluation, surface electromyographic (sEMG) measurement, and respiratory
      monitoring during swallowing. Subjects were evaluated swallowing the ODT and a
      conventional tablet formulation. Tablets were randomly and blindly presented to
      each subject. Subjects completed a preference survey subsequent to swallowing
      both tablets. RESULTS: Significant differences included greater sEMG amplitude
      and longer apneic duration when swallowing a conventional tablet compared with
      the ODT (P<.001). Patients with dysphagia demonstrated significantly longer total
      swallow durations (P<.001), a higher number of swallows per tablet (P<.002), and
      the need for fluid to assist in the clearance of the conventional tablet
      (P<.001). No significant difference was noted between the 2 tablet preparations
      in amount of residue or airway compromise during or following the swallow. On a
      postevaluation survey, patients reported that they preferred the ODT preparation
      for most of the parameters assessed. CONCLUSIONS: Patients with dysphagia
      frequently complain of trouble swallowing medication. In this study, an ODT
      formulation provided a method of delivery that required less effort to swallow,
      did not result in increased levels of airway compromise, and was preferred by
      dysphagic patients. The ODT medication delivery technology may provide benefit to
      adults with dysphagia in convenience, compliance, and accuracy of dosing.

PMID- 16301369
TI  - Differences between orthonasal and retronasal olfactory functions in patients
      with loss of the sense of smell.
AB  - OBJECTIVE: To investigate differences between orthonasal and retronasal olfaction
      in patients with loss of the sense of smell without taste complaints. DESIGN:
      Electrophysiological and psychophysical testing of orthonasal and retronasal
      olfactory functions. SETTING: Outpatient clinics. PATIENTS: A series of 18
      patients who had olfactory loss due to various reasons but no "taste" complaints.
      MAIN OUTCOME MEASURES: Orthonasal and retronasal olfactory functions assessed by
      olfactory event-related potentials and psychophysical smell tests. RESULTS:
      Psychophysical testing revealed retronasal olfaction to be normal or slightly
      altered, whereas orthonasal olfaction was either absent or severely compromised.
      Findings from nasal endoscopic examinations and computed tomographic scans were
      within the reference range in all subjects. In response to orthonasal stimulation
      there were neither detectable olfactory event-related potentials nor any with
      small amplitudes, whereas olfactory event-related potentials in response to
      retronasal stimulation were clearly present in some patients. CONCLUSION: These
      clinical observations, together with the psychophysical and electrophysiological
      findings, suggest that orthonasal and retronasal olfaction might be processed
      differently.

PMID- 16301370
TI  - Otopathogenic Pseudomonas aeruginosa strains as competent biofilm formers.
AB  - OBJECTIVE: To determine whether Pseudomonas aeruginosa, a common cholesteatoma
      pathogen, known to form biofilms in other chronic infections, is capable of
      contributing to biofilm formation in cholesteatoma. DESIGN: We tested 12 OPPA
      isolates for several aspects of biofilm formation, including adherence to human
      keratinocytes, expression of quorum-sensing genes, twitching motility, and
      production of extracellular matrix as determined by both crystal violet staining
      and carbazole reaction. RESULTS: Ten OPPA strains demonstrated increased
      adherence (1.5- to 12-fold) to human keratinocytes relative to PAO1, a laboratory
      strain. Expression of las and rhl quorum-sensing products were detected in 11
      OPPA strains. By crystal violet staining, we found biofilm formation in all OPPA
      strains equal to or greater than that found in PAO1 (2- to 18-fold). In addition,
      OPPA strains demonstrated mucoid characteristics, including down-regulation of
      twitching motility and increased alginate production. CONCLUSIONS: Strains of
      OPPA isolated from cholesteatoma are strongly adherent to keratinocytes and
      capable of forming biofilm. In addition, OPPA strains have mucoid characteristics
      in vitro. When these bacteria assume a biofilm phenotype, they are highly
      resistant to antibiotics and host defenses. These data suggest that OPPA can
      contribute to biofilm formation in cholesteatoma, leading to the persistence of
      this infection.

PMID- 16301371
TI  - Altered pigment epithelium-derived factor and vascular endothelial growth factor
      levels in lymphangioma pathogenesis and clinical recurrence.
AB  - OBJECTIVE: To determine the role of angiogenesis in the clinical behavior and
      pathogenesis of lymphangioma tumors. DESIGN: A retrospective study. Median follow
      up period was 44.5 months. SETTING: Children's Memorial Hospital, Chicago, Ill.
      PATIENTS: Tumor specimens from 12 pediatric patients who underwent surgical
      excision of cervicofacial lymphangioma were examined for expression of angiogenic
      inducer vascular endothelial growth factor (VEGF) and angiogenic inhibitor
      pigment epithelium-derived factor (PEDF) using immunohistochemical analysis.
      Specimens were divided into recurrent and nonrecurrent tumors based on clinical
      information. MAIN OUTCOME MEASURES: Staining patterns of VEGF and PEDF were
      evaluated in lymphangioma specimens. Staining patterns were then compared in both
      recurrent and nonrecurrent groups and graded in a blinded fashion. Histological
      evidence of increased angiogenesis including microvascular density, stromal
      fibrosis, and inflammation were graded in each group and correlated with
      recurrence. RESULTS: Lymphangioma specimens demonstrated histological evidence of
      increased angiogenic activity including multiple areas of increased VEGF staining
      combined with little PEDF staining. Sex, age at onset, or tumor location did not
      correlate with recurrence. Furthermore, recurrent specimens had increased
      histological evidence of angiogenesis as well as increased VEGF and decreased
      PEDF activity compared with nonrecurrent lesions. CONCLUSIONS: Lymphangiomas
      exhibit tumorlike pathogenesis owing to the high expression of angiogenic
      inducers compared with the low expression of inhibitors. Recurrence may be
      influenced by this imbalance of angiogenic mediators. Further research with
      antiangiogenic therapy using agents such as PEDF analogues or anti-VEGF receptor
      antibodies is indicated because they may stabilize or suppress the growth of
      these neoplasms.

PMID- 16301372
TI  - Vertigo and imbalance in children: a retrospective study in a Helsinki University
      otorhinolaryngology clinic.
AB  - OBJECTIVE: To determine medical characteristics of children with vertigo who
      visited an otorhinolaryngology (ENT) clinic during a 5-year period. DESIGN: A
      retrospective chart review carried out between 2000 and 2004. SETTING: Helsinki
      University Central Hospital tertiary referral center ENT clinic. SUBJECTS: A
      total of 119 children (63 girls and 56 boys), ranging in age from 7 months to 17
      years (mean age, 10.9 years at examination). MAIN OUTCOME MEASURES: Patients were
      identified from the ENT clinic database based on hospital discharge codes, with
      data stored in the database and the SPSS program applied for statistical
      analysis. RESULTS: Only 0.7% of children visiting the hospital during the 5-year
      period had vertigo. Benign paroxysmal vertigo of childhood, migraine-associated
      dizziness, vestibular neuronitis, and otitis media-related dizziness accounted
      for vertigo in most of the children. CONCLUSIONS: Vertigo is a rare primary
      complaint of children in an ENT clinic. In achieving a diagnosis, the most
      valuable tools are medical history, an otoneurologic examination,
      electronystagmography, and audiography.

PMID- 16301374
TI  - Distribution of type IV collagen in the cochlea in Alport syndrome.
AB  - OBJECTIVE: To determine the distribution of alpha1, alpha3, and alpha5 chains of
      type IV collagen in the cochlea in Alport syndrome. DESIGN: Case-control study.
      PATIENTS: Two patients with sensorineural hearing loss due to Alport syndrome.
      Both patients had known mutations in the COL4A5 gene. MAIN OUTCOME MEASURES:
      Immunostaining was used to study the distribution of type IV collagen (alpha1,
      alpha3, and alpha5 chains) within the cochlea. Immunostaining was also performed
      in the cochlear tissues of an unaffected individual used as a control. RESULTS:
      In the control ear, alpha1 staining was observed in the basement membrane
      overlying the basilar membrane, in the basement membrane of cochlear blood
      vessels and Schwann cells, and within the spiral limbus. In the control ear, we
      also observed strong staining for alpha3 and alpha5 chains in the basement
      membrane overlying the basilar membrane and within the spiral ligament. In both
      cases with Alport syndrome, no immunostaining was observed for alpha3 or alpha5
      chains within the cochlea, whereas alpha1 staining was present in locations
      similar to that seen in the control ear. CONCLUSIONS: The results indicate that
      isotype switching does not occur within the cochlea in Alport syndrome. The
      results are also consistent with the hypothesis that the sensorineural hearing
      loss in Alport syndrome may be due to alterations in cochlear micromechanics
      and/or dysfunction of the spiral ligament.

PMID- 16301373
TI  - Evaluation of importance of Toll-like receptor 4 in acute Streptococcus
      pneumoniae sinusitis in mice.
AB  - OBJECTIVES: To investigate the effect of RC-527, a synthetic toll-like receptor 4
      (TLR4) agonist, on stimulating the immune response before acute Streptococcus
      pneumoniae sinusitis in a mouse model, and to determine the importance of TLR4 in
      modulating the response to S. pneumoniae. Toll-like receptor 4 agonists have been
      shown to induce protective innate immune responses when administered before some
      bacterial or viral challenges in mice. DESIGN: We intranasally inoculated BALB/c,
      TLR4 complex-deficient C3H/HeJ, and wild-type C3H/HeOuJ mice with S. pneumoniae
      24 hours after treatment with 10 or 1 microg of RC-527 or vehicle. Bacterial
      counts from nasal lavage culture and the cell markers GR1, CD11b, CD3, CD4, and
      CD8 in sinus tissue were quantified at postinoculation days 2, 5, and 14. MAIN
      OUTCOME MEASURE: Immune response induced by RC-527. RESULTS: Treatment with RC
      527 induced an immune response through TLR4, as demonstrated by recruitment of
      phagocytes in uninfected wild-type C3H/HeOuJ mice, but not in TLR4 complex
      deficient C3H/HeJ mice. The immune response was also demonstrated by a
      significant increase of CD3+, CD4+, and CD8+ T cells in infected and uninfected
      wild-type C3H/HeOuJ mice, but not in TLR4 complex-deficient C3H/HeJ mice.
      However, the enhancement of the immune response induced by the TLR4 agonist
      showed a limited effect on bacterial clearance. CONCLUSIONS: Our studies in mice
      suggest that stimulation of TLR4 plays a minor role in the overall response to S.
      pneumoniae infection of the upper airway, and stimulating this receptor before
      infection does not significantly enhance the immune response of immunocompetent
      mice to clear S. pneumoniae infection.

PMID- 16301375
TI  - The effect of body position on sleep apnea in children younger than 3 years.
AB  - OBJECTIVE: To determine the association between body position and obstructive
      events during sleep as determined by polysomnography (PSG) in very young children
      (age, < or = 3 years) with obstructive sleep apnea syndrome. DESIGN:
      Retrospective chart review. SUBJECTS: Children aged 3 years and younger who
      underwent PSG to evaluate obstructive sleep apnea and subsequently underwent
      adenotonsillectomy between December 1, 2000, and November 30, 2003, were included
      in the study. The PSGs were analyzed for data on the respiratory disturbance
      index (RDI), time spent in each body position, number of apneic events in each
      position, oxygen saturation, and time spent in each stage of sleep. The results
      determined the statistical significance of these parameters. RESULTS: Sixty
      patients satisfied the criteria for inclusion in the study. The mean supine sleep
      RDI was 8.5 compared with 4.9 for the mean nonsupine sleep RDI. The mean RDI
      increased from 5.6 to 8.5 when more than 50% of the time was spent in supine
      sleep. There was a further increase to 10.5 when supine sleep increased to 75% of
      the total sleep time. The mean RDI in rapid eye movement sleep was 20.5 compared
      with 5.3 in non-rapid eye movement sleep. The mean +/- SD supine sleep RDI was
      18.5 +/- 5.1, and the mean nonsupine RDI was 7.2 +/- 1.9, which was statistically
      significant (P = .02). CONCLUSIONS: There is an increase in the RDI with
      increased time spent in supine sleep in very young children with obstructive
      sleep apnea. Inadequate time spent in that position may lead to an
      underestimation of the severity of obstructive sleep apnea. A combination of
      reduced rapid eye movement sleep and increased nonsupine sleep may invalidate the
      findings of PSG in these children.

PMID- 16301376
TI  - Microbiology of intracranial abscesses and their associated sinusitis.
AB  - OBJECTIVE: To evaluate the organisms recovered from infected sinuses and
      associated intracranial abscesses (IAs). DESIGN: Retrospective review of findings
      from aspirate of pus from 10 infected sinuses and their corresponding IAs.
      SETTING: Academic medical center. PATIENTS: Ten patients diagnosed as having
      sinusitis (age range, 7-58 years). MAIN OUTCOME MEASURE: Aerobic and anaerobic
      bacteria findings from infected sinuses and IAs. RESULTS: Polymicrobial flora was
      found in 9 sinuses and 8 IAs. Anaerobes were isolated from all sinuses and 9 IAs.
      A total of 26 isolates (2.6 isolates per specimen) were recovered from the
      sinuses: 19 anaerobic, 6 aerobic or facultative, and 1 microaerophilic; 17
      isolates were found in the IAs (1.7 isolates per site): 13 anaerobic, 2 aerobic
      or facultative, and 2 microaerophilic. The predominant anaerobes were
      Fusobacterium species (in 5 corresponding sinuses and abscesses, 1 in a sinus
      only, and 1 in an IA only), Prevotella species (in 3 corresponding sinuses and
      abscesses), Peptostreptococcus species (in 2 corresponding sinuses and abscesses,
      and 4 in a sinus only), Staphylococcus aureus, Haemophilus influenzae type b,
      microaerophilic streptococci, and Bacteroides ureolyticus (in 1 corresponding
      sinus and abscess each). Streptococcus pneumoniae was recovered 2 times, only
      from a sinus. Alpha-hemolytic streptococci and beta-hemolytic streptococci group
      F were each isolated once from the sinus. Concordance in the microbiological
      findings between the sinus and the IA was found in all instances. However,
      certain organisms were present at only one or the other site. CONCLUSION: These
      data illustrate the concordance in the recovery of organisms from infected
      sinuses and their associated IA and confirm the importance of anaerobic bacteria
      in sinusitis and IA.

PMID- 16301377
TI  - Prelingual siblings of children with GJB2 hearing loss: issues to consider.

PMID- 16301378
TI  - Radiology quiz case 1. Melanotic-type mucosal malignant melanoma (MMM).

PMID- 16301379
TI  - Radiology quiz case 2. Facial nerve schwannoma.

PMID- 16301380
TI  - Radiology quiz case 3. Hydatid cyst of the neck.

PMID- 16301381
TI  - Radiology quiz case 4. Intramuscular angioma (IMA).

PMID- 16301382
TI  - Multiple apocrine hidrocystoma of the face treated with a 1450-nm diode laser.

PMID- 16301383
TI  - Imiquimod treatment of exuberant granulation tissue in a nonhealing diabetic
      ulcer.

PMID- 16301384
TI  - The effect of short-contact topical tretinoin therapy for foot ulcers in patients
      with diabetes.
AB  - OBJECTIVE: To determine the efficacy and safety of short-contact administration
      of topical tretinoin on foot ulcers in patients with diabetes. DESIGN:
      Randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinic at
      a Veterans Affairs medical center. PATIENTS: Twenty-four volunteers with diabetic
      foot ulcers but without evidence of peripheral arterial disease or infection.
      INTERVENTIONS: Patients were randomized to 4 weeks of daily treatment with either
      topical 0.05% tretinoin solution (Retin-A) or placebo saline solution.
      Photographs and assessment of wound size and appearance were assessed every 2
      weeks for a total of 16 weeks. MAIN OUTCOME MEASURES: The proportion of ulcers
      that healed in each group and the degree of change in ulcer size. RESULTS: Twenty
      two patients, with a total of 24 foot ulcers, completed the study. At the end of
      16 weeks, 2 (18%) of 11 ulcers in the control group and 6 (46%) of 13 ulcers in
      the tretinoin treatment group healed completely. Topical tretinoin therapy
      significantly decreased ulcer area and depth compared with placebo treatment over
      the 16 weeks of the study (P < .01 for surface area; P = .02 for depth). Adverse
      effects mainly consisted of mild pain at the ulcer site. CONCLUSIONS: Short
      contact application of topical tretinoin improved the healing of foot ulcers in
      patients with diabetes. The tretinoin therapy was generally well tolerated,
      without serious local or systemic adverse effects.

PMID- 16301385
TI  - The spectrum of Spitz nevi: a clinicopathologic study of 83 cases.
AB  - OBJECTIVE: To achieve a clinicopathologic classification of Spitz nevi by
      comparing their clinical, dermoscopic, and histopathologic features. DESIGN:
      Eighty-three cases were independently reviewed by 3 histopathologists and
      preliminarily classified into classic or desmoplastic Spitz nevus (CDSN, n = 11),
      pigmented Spitz nevus (PSN, n = 14), Reed nevus (RN, n = 16), or atypical Spitz
      nevus (ASN, n = 14); the remaining 28 cases were then placed into an intermediate
      category (pigmented Spitz-Reed nevus, PSRN) because a unanimous diagnosis of
      either PSN or RN was not reached. SETTING: University dermatology and pathology
      departments and general hospital pathology departments. PATIENTS: A sample of
      subjects with excised melanocytic lesions. MAIN OUTCOME MEASURE: Frequency of
      dermoscopic patterns within the different histopathologic subtypes of Spitz nevi.
      RESULTS: Overlapping clinical, dermoscopic, and histopathologic findings were
      observed among PSN, RN, and PSRN, thereby justifying their inclusion into the
      single PSRN diagnostic category. Asymmetry was the most frequent indicator of
      histopathologic ASN (79%; n = 11); in only 4 cases did dermoscopic asymmetry show
      no histopathologic counterpart, and in those cases the discrepancy was probably
      the result of an artifact of the gross sampling technique carried out with no
      attention to the dermoscopic features. CONCLUSIONS: Among Spitz nevi,
      histopathologic distinction between PSN and RN is difficult, not reproducible,
      and may be clinically useless. A simple clinicopathologic classification of these
      neoplasms might therefore be structured as CDSN, PSRN, and ASN. Asymmetry should
      be assessed using both dermoscopic and histopathologic analysis, and reliability
      in histopathologic diagnosis may be enhanced by the simultaneous evaluation of
      the corresponding dermoscopic images.

PMID- 16301386
TI  - The performance of SolarScan: an automated dermoscopy image analysis instrument
      for the diagnosis of primary melanoma.
AB  - OBJECTIVE: To describe the diagnostic performance of SolarScan (Polartechnics
      Ltd, Sydney, Australia), an automated instrument for the diagnosis of primary
      melanoma. DESIGN: Images from a data set of 2430 lesions (382 were melanomas;
      median Breslow thickness, 0.36 mm) were divided into a training set and an
      independent test set at a ratio of approximately 2:1. A diagnostic algorithm
      (absolute diagnosis of melanoma vs benign lesion and estimated probability of
      melanoma) was developed and its performance described on the test set. High
      quality clinical and dermoscopy images with a detailed patient history for 78
      lesions (13 of which were melanomas) from the test set were given to various
      clinicians to compare their diagnostic accuracy with that of SolarScan. SETTING:
      Seven specialist referral centers and 2 general practice skin cancer clinics from
      3 continents. Comparison between clinician diagnosis and SolarScan diagnosis was
      by 3 dermoscopy experts, 4 dermatologists, 3 trainee dermatologists, and 3
      general practitioners. PATIENTS: Images of the melanocytic lesions were obtained
      from patients who required either excision or digital monitoring to exclude
      malignancy. MAIN OUTCOME MEASURES: Sensitivity, specificity, the area under the
      receiver operator characteristic curve, median probability for the diagnosis of
      melanoma, a direct comparison of SolarScan with diagnoses performed by humans,
      and interinstrument and intrainstrument reproducibility. RESULTS: The melanocytic
      only diagnostic model was highly reproducible in the test set and gave a
      sensitivity of 91% (95% confidence interval [CI], 86%-96%) and specificity of 68%
      (95% CI, 64%-72%) for melanoma. SolarScan had comparable or superior sensitivity
      and specificity (85% vs 65%) compared with those of experts (90% vs 59%),
      dermatologists (81% vs 60%), trainees (85% vs 36%; P =.06), and general
      practitioners (62% vs 63%). The intraclass correlation coefficient of
      intrainstrument repeatability was 0.86 (95% CI, 0.83-0.88), indicating an
      excellent repeatability. There was no significant interinstrument variation (P =
      .80). CONCLUSIONS: SolarScan is a robust diagnostic instrument for pigmented or
      partially pigmented melanocytic lesions of the skin. Preliminary data suggest
      that its performance is comparable or superior to that of a range of clinician
      groups. However, these findings should be confirmed in a formal clinical trial.

PMID- 16301387
TI  - In vivo confocal scanning laser microscopy of a series of congenital melanocytic
      nevi suggestive of having developed malignant melanoma.
AB  - OBJECTIVE: To determine the utility of confocal scanning laser microscopy (CSLM)
      in the in vivo evaluation of congenital melanocytic nevi (CMNs) that are
      suggestive of having developed melanoma. DESIGN: The CMNs suggestive of melanoma
      by clinical and dermoscopic examination were imaged by CSLM, and the findings
      correlated with the features seen on dermoscopic and histologic examination.
      SETTING: Dermatology clinic specializing in pigmented lesions. PATIENTS: Seven
      patients with clinically irregular small to medium CMNs. INTERVENTIONS: The areas
      imaged by CSLM were sampled with 3-mm punch biopsy specimens. The entire lesion
      was subsequently excised. The punch biopsy specimens were step sectioned
      horizontally to correlate with the CSLM images. Excised samples were step
      sectioned and processed routinely. Histologic features observed on CSLM were
      correlated with the features seen on dermoscopic and light microscopic
      examination. MAIN OUTCOME MEASURE: Correlation of the structures seen using CSLM
      with the dermoscopic and histologic features of CMNs and melanoma. RESULTS: The
      CSLM illustrated histologic characteristics of CMNs, including the presence of
      hyperpigmented keratinocytes, nevus cells, melanophages, and a normal "honeycomb"
      epidermal architecture. Features suggestive of melanoma were not evident by CSLM
      in 6 histologically proven benign CMNs. Histologic features associated with
      melanoma, such as an increased number of intraepidermal atypical melanocytes
      (pagetoid) and loss of normal epidermal cellular architecture, were identified by
      CSLM in 1 lesion, which on histologic analysis revealed melanoma in association
      with a CMN. CONCLUSION: Our results illustrate that CSLM may be useful for
      clinicopathologic correlations and for the preliminary noninvasive diagnosis of
      pigmented neoplasms in vivo.

PMID- 16301388
TI  - Specific dermoscopy patterns and amplifications of the cyclin D1 gene to define
      histopathologically unrecognizable early lesions of acral melanoma in situ.
AB  - OBJECTIVE: To define early lesions of acral melanoma in situ that cannot be
      recognized histopathologically. DESIGN: A retrospective review of the clinical,
      dermoscopic, and histopathological findings. SETTING: University department of
      dermatology. PATIENTS: Thirty-three patients with melanocytic lesions on acral
      volar skin that were clinically suspected of being early melanomas. MAIN OUTCOME
      MEASURES: Fluorescent in situ hybridization studies to detect the cyclin D1 gene
      amplification in proliferating melanocytes, which is a characteristic genetic
      aberration recently found in acral melanoma. RESULTS: Seventeen of 33 lesions
      were histopathologically diagnosed as either melanoma in situ (8 lesions) or
      benign melanocytic nevi (9 lesions). Amplification of the cyclin D1 gene was
      observed in 2 (25%) of the 8 melanomas in situ. None of the 9 nevi showed the
      amplification. The remaining 16 lesions were, however, difficult to classify
      histopathologically because most of them showed only a slight increase of
      nonatypical melanocytes in the basal cell layer of the epidermis. On dermoscopic
      examination, 9 of these 16 lesions exhibited the parallel ridge pattern that has
      been reported to be highly specific to melanoma in situ, and 4 (44%) of them had
      amplifications of the cyclin D1 gene. Amplifications were not found in any of the
      remaining 7 lesions that showed dermoscopic patterns suggestive of melanocytic
      nevi. CONCLUSIONS: Cyclin D1 gene amplification detected by fluorescent in situ
      hybridization identified a very early progression phase of acral melanoma that
      precedes histopathologically defined melanoma in situ. The present study also
      indicates the specificity of the parallel ridge pattern on dermoscopy to detect
      melanomas on acral volar skin at such a very early developmental phase.

PMID- 16301389
TI  - Association of clinical progression in classic Kaposi's sarcoma with reduction of
      peripheral B lymphocytes and partial increase in serum immune activation markers.
AB  - OBJECTIVE: To evaluate various immunologic markers in the peripheral blood of
      patients with early and advanced classic Kaposi's sarcoma (CKS). DESIGN: Cross
      sectional study. SETTING: A major referral center for skin and venereal diseases.
      PATIENTS: Sixty-eight patients with histologically confirmed CKS staged according
      to a modified version of the Mitsuyasu-Groopman classification in stage I-II
      (cutaneous involvement only) and stage IV (skin and systemic involvement). MAIN
      OUTCOME MEASURES: Concentrations of neopterin and beta2-microglobulin, titer of
      anti-human herpesvirus 8 antibodies, number of natural killer cells, and numbers
      of total lymphocytes, B lymphocytes, T lymphocytes, and their subsets in
      peripheral blood. RESULTS: The median values of beta2-microglobulin and neopterin
      were elevated in patients with CKS in stage IV (median, 3.679 microg/mL [312.72
      nmol/L] and 14.0 nmol/L, respectively) compared with patients in stage I-II
      (median, 2.406 microg/mL [204.51 nmol/L] and 6.5 nmol/L, respectively). A
      statistically significant reduction in total lymphocyte and B-lymphocyte counts
      was observed in patients with advanced-stage CKS (1679/microL and 79/microL,
      respectively) compared with patients in earlier stages of the disease
      (2142/microL and 224/microL, respectively). The human herpesvirus 8 antibody
      titer, determined by latent immunofluorescent assay, decreased from stage I-II to
      stage IV, although not at a statistically significant level (P = .14).
      CONCLUSION: The evolution of CKS from the early stages of the disease to the more
      advanced may be associated with a partial activation of the immune system and a
      gradual decrease in the number of total and B lymphocytes.

PMID- 16301390
TI  - Infection with Kaposi's sarcoma-associated herpesvirus among families of patients
      with classic Kaposi's sarcoma.
AB  - BACKGROUND: Classic Kaposi's sarcoma (CKS) primarily affects elderly
      Mediterranean or Eastern European men. Incidence rates of CKS in Israel are among
      the world's highest. In practically all cases, antibodies against Kaposi's
      sarcoma-associated herpesvirus (KSHV) can be detected. A relatively high
      seroprevalence rate of KSHV in Israel generally correlates with the incidence of
      CKS. A sexual mode of virus transmission is recognized among homosexual men,
      whereas the precise transmission routes in the heterosexual population and those
      with CKS are still unclear. OBJECTIVE: To better assess the transmission routes
      of KSHV in Israeli patients with CKS and their first-degree relatives as compared
      with a control group. DESIGN: Serum was collected from all study participants and
      tested for KSHV antibodies by means of latent and lytic immunofluorescence
      assays. An open reading frame 65 (ORF65) Western blot assay was applied as a
      confirmatory tool. SETTING: Three dermatological departments in Israel. PATIENTS:
      Sixty-four Jewish patients with CKS, 143 of their first-degree relatives, and 186
      hospital-based control subjects. RESULTS: Seropositivity to KSHV was detected in
      62 (96.9%) of the patients with CKS, in 56 (39.2%) of their first-degree
      relatives, and in only 21 (11.3%) of the hospital controls (P<.001). The specific
      relationship with the index patient (spouse, offspring, or sibling) had no
      significant effect on the prevalence of serpositivity in the family members.
      CONCLUSION: Our serologic evidence of familial clustering of KSHV infection
      suggests a predominantly nonsexual horizontal transmission route of the virus.

PMID- 16301391
TI  - Soft tissue cervicofacial emphysema after dental treatment: report of 2 cases
      with emphasis on the differential diagnosis of angioedema.
AB  - BACKGROUND: The development of soft tissue cervicofacial emphysema after dental
      treatment is a rare complication, with few descriptions in the dermatologic
      literature. It is usually restricted to only moderate local swelling. However,
      spread of larger amounts of air into deeper spaces may sometimes cause serious
      complications, including airway compromise due to accumulation of air in the
      retropharyngeal space, pneumomediastinum, and pneumopericardium. Fatal air
      embolism and soft tissue infections through dissemination of oral flora
      microorganisms along the emphysematous tracts have also been described.
      Therefore, early recognition is important, but the unfamiliarity of
      dermatologists with this condition often causes diagnostic problems. Important
      differential diagnoses include angioedema, soft tissue infections, and hematoma.
      OBSERVATIONS: We describe 2 patients with different severity of the emphysema and
      airway compromise, representing the wide spectrum of its clinical expression. Our
      first case was remarkable, because the emphysema was massive and extended far
      into deep spaces, including the orbita, mediastinum, and pleural cavity. The
      present case is only the third report of pneumothorax associated with dental
      treatment published to date. The patient's condition was initially misdiagnosed
      and treated as angioedema. CONCLUSIONS: Dermatologists should be aware that soft
      tissue emphysema can cause acute swelling of the cervicofacial region after
      dental procedures. Angioedema is an important differential diagnosis, because it
      may be caused by the use of nonsteroidal anti-inflammatory drugs or local
      anesthetics, which are often administered during dental treatments.

PMID- 16301392
TI  - The role of dermoscopy and digital dermoscopy analysis in the diagnosis of
      pigmented skin lesions.

PMID- 16301393
TI  - Topical negative pressure devices: use for enhancement of healing chronic wounds.
AB  - Chronic wounds present a significant challenge, because there are few available
      treatment options for timely healing. Topical negative pressure devices have been
      used in a number of different types of wounds, including chronic wounds. They are
      believed to hasten wound healing by (1) maintaining a moist environment, (2)
      removing wound exudates, (3) increasing local blood flow, (4) increasing
      granulation tissue formation, (5) applying mechanical pressure to promote wound
      closure, and (6) reducing bacterial loads in the wound. Multiple nonrandomized,
      noncontrolled studies have reported that the use of these devices results in
      faster healing times and more successful closures. Five small randomized,
      controlled trials have also shown favorable outcomes with the use of topical
      negative pressure devices compared with conventional treatment. Adverse effects
      include discomfort, pain, and excessive tissue growth into the dressing.
      Complications are limited if the device is used properly. In light of the current
      treatment options, topical negative pressure devices may be considered useful as
      adjuvant therapy for chronic wounds; however, there is inadequate definitive
      evidence that wound healing is substantially better with these devices than with
      traditional therapy.

PMID- 16301394
TI  - Painful purpuric plaques on edematous hands.

PMID- 16301395
TI  - Nonhealing verrucous plaque on the forearm.

PMID- 16301397
TI  - Facial erythema and onychoschizia.

PMID- 16301396
TI  - Erythematous plaques on the flexural surfaces.

PMID- 16301398
TI  - Association of frequent indoor UV tanning with seasonal affective disorder.

PMID- 16301399
TI  - A stomatitis due to artificial cinnamon-flavored chewing gum.

PMID- 16301400
TI  - Histologic evaluation of melanomas.

PMID- 16301401
TI  - Value of dermoscopy?

PMID- 16301402
TI  - A bipartite interaction between Pseudomonas aeruginosa and fungi in
      onychomycosis.

PMID- 16301403
TI  - A potential pathogenic role for aberrant DNA rearrangements in bridging
      dyscrasias of undetermined significance and lymphoma?

PMID- 16301404
TI  - Topical tacrolimus.

PMID- 16301405
TI  - Nutrigenomics.

PMID- 16301406
TI  - The integration of the internet, mobile phones, digital photography, and computer
      aided design software to achieve telemedical wound measurement and care.

PMID- 16301407
TI  - Oral lichen planus: mercury and its kin.

PMID- 16301408
TI  - Defective prelamin A processing resulting from LMNA or ZMPSTE24 mutations as the
      cause of restrictive dermopathy.

PMID- 16301409
TI  - Drug-induced bullous pemphigoid caused by a generic Canadian medication obtained
      over the internet.

PMID- 16301410
TI  - Combination therapy of doxycycline and topical tacrolimus for venous ulcers.

PMID- 16301411
TI  - Clinical and dermoscopic features of an evolving deep-penetrating nevus.

PMID- 16301412
TI  - In tribute. Claude H Organ, Jr.

PMID- 16301439
TI  - Notes from the field: a resident's perspective on international surgery.

PMID- 16301440
TI  - Volunteerism.

PMID- 16301441
TI  - Continuing refinements in surgical antibiotic prophylaxis.

PMID- 16301442
TI  - September 11, 2001, revisited: a review of the data.
AB  - HYPOTHESIS: The September 11, 2001, World Trade Center (WTC) attack was a
      disaster of epic proportion in New York City, NY. It was unprecedented in terms
      of the number of people who were killed in the bombings, as well as in terms of
      the volume of patients received at local (New York City) hospitals. The strain on
      local emergency medical services, hospitals, and the citywide trauma system is
      still felt today as the hospitals, physicians, and agencies involved struggle to
      train for similar events that may occur in the future, cope with the
      psychological and social aftermath, and even pay for the response to the bombing.
      The objective of this review of the data was to determine the major causes of
      morbidity (ie, hospital visits) during the hours immediately after the September
      11, 2001, WTC attack, as well as to detail the costs involved in the medical
      response to a disaster of this scale and to identify some lessons learned with
      respect to the hospital's response to an event of this magnitude. DESIGN: Review
      of records and cost data submitted by Saint Vincent's Hospital, Manhattan, NY, to
      the state of New York and federal sources for financial relief from the September
      11, 2001, WTC attack. SETTING: Saint Vincent's Hospital is an academic medical
      center of New York Medical College and a New York City-designated level I trauma
      center. PATIENTS: All medical records for the patients registered at Saint
      Vincent's Hospital on September 11, 2001, after 8:50 am were reviewed. RESULTS:
      The major cause of morbidity for the September 11, 2001, patients was smoke
      inhalation (30.0%); followed closely by chemical conjunctivitis and corneal
      abrasions (16%); lacerations, abrasions, and soft-tissue injuries (15.5%);
      isolated orthopedic complaints (12%); and psychiatric complaints (10%). Multiple
      trauma patients were 3% of the patients seen. There were 5 fatalities at Saint
      Vincent's Hospital. CONCLUSIONS: The WTC disaster was a source of major morbidity
      and mortality to the people of New York City. The possibility that Saint
      Vincent's will again serve in that role is in the forefront of the minds of
      everyone involved in updating our contingency plan.

PMID- 16301443
TI  - Women authors of surgical research.
AB  - HYPOTHESIS: The number of women authors in the surgical literature has increased
      during the past 20 years. DESIGN: Randomly selected issues of odd-year journals
      in Archives of Surgery and Annals of Surgery from January 1, 1985, to December
      31, 2003, were reviewed. We determined the gender of each author and reported
      trends in the occurrence of women authors over time. RESULTS: The percentage of
      women authors has increased over time and parallels the percentage of women
      faculty in academic surgery positions. A much higher percentage of women authors
      than men authors are nonphysicians. The trend for increased authorship by women
      over time was significant in Archives of Surgery. CONCLUSION: Although the number
      of women first authors is low, their contributions to the field of surgery should
      be acknowledged, and efforts to provide women with the resources and
      opportunities to conduct research and publish their findings should be a focus
      for surgical departments looking to increase their research productivity.

PMID- 16301444
TI  - Classifying surgical complications: a critical appraisal.
AB  - HYPOTHESIS: Inconsistency exists in methods of classifying complications after
      colorectal surgery with anastomosis, which may result in incomplete availability
      of data. DESIGN: Retrospective study. SETTING: Nonuniversity teaching hospital.
      PATIENTS: All patients with complications after colorectal surgery with
      anastomosis performed from January 1, 1995, through December 31, 2001.
      INTERVENTIONS: Incidence and type of complications and classification systems
      used were recorded. Complications were classified according to the systems of the
      Association of Surgery of The Netherlands and the Trauma Registry of the American
      College of Surgeons. MAIN OUTCOME MEASURES: Classification of complications and
      systems used to record them. RESULTS: Colorectal surgery was performed in 505
      patients. In 181 patients, 437 complications were recorded, and 350 (80%) of
      these events represented 13 types of complications. Different classification
      systems were used, and no consistent approach in classifying was seen.
      Anastomotic disruption (n = 40), the most serious complication after colorectal
      surgery, was recorded as dehiscence 32 times (80%) in the Association of Surgery
      of The Netherlands system and as anastomotic leak (code 4001) 24 times (60%) in
      the Trauma Registry of the American College of Surgeons system. CONCLUSIONS:
      Diverse classification systems were used for major complications after colorectal
      surgery. The differences in classifying seemed to be based on the interpretation
      of the recording physician. Emphasis should be placed on training physicians on a
      regular basis in documenting and classifying complications and providing
      feedback. The reporting process should focus on adequate and uniform classifying
      of events with major significance, eg, anastomotic disruption in colorectal
      surgery.

PMID- 16301445
TI  - Variation in the use of laparoscopic cholecystectomy for acute cholecystitis: a
      population-based study.
AB  - HYPOTHESIS: There is wide variation in the use of laparoscopic cholecystectomy
      (LC) for acute cholecystitis among all public hospitals in Hong Kong. The
      objective of this study was to determine the factors responsible for the use of
      LC for acute cholecystitis in a stable population. DESIGN: A retrospective survey
      on 2353 patients with pathologically proven acute cholecystitis treated with
      cholecystectomy in Hong Kong from 1998 to 2002. SETTING: All public hospitals in
      Hong Kong. RESULTS: The rate of using LC for acute cholecystitis increased by
      30.4% from 1998 to 2002. We observed a wide variation in the use of LC for acute
      cholecystitis ranging from 3.7% to 92.9% (P<.001). There was no correlation
      between the number of cholecystectomies performed and the percentage of LCs
      performed in each hospital (P = .39). Logistic regression analysis showed that
      the hospital, year of operation, and age of the patients were independent
      variables for LC. CONCLUSIONS: A wide variation in the use of LC for acute
      cholecystitis was observed among the public hospitals in Hong Kong. Young female
      patients from selected hospitals recently are more likely to be treated with LC.

PMID- 16301446
TI  - Cardiac surgery in octogenarians: does age alone influence outcomes?
AB  - HYPOTHESIS: Outcome differences in octogenarians vs patients younger than 80
      years undergoing coronary artery bypass grafting or valve surgery can be analyzed
      to isolate the effect of age alone on morbidity and mortality. DESIGN: Eight-year
      hospitalization cohort study. Physicians, nurses, and perfusionists prospectively
      collected data on 225 variables. SETTING: Community hospital. PATIENTS: A
      consecutive sample of 7726 patients undergoing coronary artery bypass grafting or
      valve surgery between October 1, 1993, and February 28, 2001. MAIN OUTCOME
      MEASURES: There were 9 main outcomes of interest: mortality, length of hospital
      stay, gastrointestinal tract complications, neurologic complications, pulmonary
      complications, renal complications, return to intensive care unit, intraoperative
      complications, and reoperation to treat bleeding. We controlled for 16 potential
      confounding variables to isolate outcome differences according to age. RESULTS:
      Of 7726 patients who fit the inclusion criteria, 522 were octogenarians. Compared
      with nonoctogenarians, octogenarians had a significantly higher New York Heart
      Association functional classification, higher incidence of hypertension, and
      underwent a greater number of coronary artery bypass grafting plus valve surgical
      procedures (P<.05). They also had significantly lower body surface area, fewer
      total number of grafts used, less history of tobacco use, and less abnormal left
      ventricular hypertrophy, and there were fewer nonwhite patients and fewer men. At
      multivariate analysis, octogenarians had a higher risk for death (relative risk
      [RR], 1.72; 95% confidence interval [CI], 1.52-1.83), longer hospital stay (RR,
      1.03; 95% CI, 1.01-1.04), more neurologic complications (RR, 1.51; 95% CI, 1.26
      1.67), and were more likely to undergo a reoperation to treat bleeding (RR, 1.49;
      95% CI, 1.09-1.72). Univariate analyses revealed no difference between
      octogenarians and nonoctogenarians for diabetes mellitus, urgency of procedure,
      prior myocardial infarction, time since last myocardial infarction,
      cerebrovascular history, chronic obstructive pulmonary disease, or pump time.
      CONCLUSIONS: Age alone has been shown to influence outcomes after cardiac bypass
      or valve surgery. Octogenarians undergoing cardiac surgery have more
      comorbidities and higher mortality even after controlling for 16 potential
      confounding variables, compared with nonoctogenarians.

PMID- 16301447
TI  - Effect of antecolic reconstruction on delayed gastric emptying after the pylorus
      preserving Whipple procedure.
AB  - HYPOTHESIS: Antecolic duodenojejunostomy prevents delayed gastric emptying (DGE)
      after a pylorus-preserving Whipple (ppW) procedure better than retrocolic
      duodenojejunostomy. DESIGN: A single operation team's experience with antecolic
      and retrocolic duodenojejunostomy in ppW is analyzed on a prospective database
      using univariate and multivariate models. SETTING: Tertiary referral center that
      focuses on pancreatic diseases. PATIENTS AND INTERVENTIONS: One hundred
      consecutive patients undergoing a ppW procedure with retrocolic reconstruction
      between January 1, 1996, and December 31, 2001, and 100 consecutive patients
      undergoing a ppW procedure with antecolic reconstruction between January 1, 2002,
      and December 31, 2003. Characteristics such as median age, median hospital stay,
      sex, diagnosis, previous operations, blood loss, surgical and medical
      complications, American Society of Anesthesiologists risk groups, stent
      implantation, and especially DGE were matched for the comparison groups. MAIN
      OUTCOME MEASURES: We compared DGE, characteristics, and perioperative variables
      in patients with antecolic vs retrocolic reconstruction after ppW. RESULTS: The
      DGE occurred significantly more often in patients with retrocolic reconstruction
      than in those with antecolic reconstruction (P < .001). The antecolic and
      retrocolic study groups were comparable in age (P = .25), sex (P = .48), and
      postoperative surgical (P = .19) and medical (P = .054) complications. The
      univariate analysis between patients with and without DGE did not show
      significant differences regarding diagnosis, previous operations, blood loss,
      surgical and medical complications, American Society of Anesthesiologists
      classification, or stent implantation. In the multivariate analysis, only the
      type of reconstruction (P = .006) and sex (P = .04) seemed to affect DGE.
      CONCLUSION: We recommend antecolic duodenjejunostomy in patients undergoing a ppW
      procedure regardless of their diagnosis.

PMID- 16301448
TI  - Extension of right portal vein embolization to segment IV portal branches.
AB  - HYPOTHESIS: Routine embolization of segment IV, combined with right portal vein
      embolization (PVE), has been suggested in patients who are candidates for right
      trisegmentectomy to induce higher and faster hypertrophy of segments II-III. Our
      objective was to compare hypertrophy of segments II-III induced by PVE with and
      without extension to segment IV in patients undergoing major hepatectomy.
      METHODS: Twenty-six consecutive patients were prospectively evaluated; the future
      remnant liver volume was calculated using the portal phase of spiral computed
      tomographic scans before and 3 to 4 weeks after right PVE (group R, n = 13),
      which was extended to segment IV branches in 13 patients (group L). RESULTS:
      Twenty patients (76.9%) underwent the scheduled hepatic resection. Of the 6
      patients who did not undergo the planned operation, 5 showed disease progression;
      in 1 patient (group L), there was an insufficient increase of the future remnant
      liver volume due to the presence of embolizing material in the left lobe. The
      mean +/- SD time between PVE and volume measurements was 31.8 +/- 9.3 days. The
      overall mean +/- SD future remnant liver volume increase was 53.1% +/- 24.8%; the
      increase for segment IV was significantly higher in group R than group L. The
      mean +/- SD post-PVE volumes of segments II-III and the rate of volume increase
      were similar in the 2 groups: group R, 348.4 +/- 83.1 cm3 and 67.8% +/- 30.8%,
      respectively, vs group L, 391.2 +/- 78.05 cm3 and 56.1% +/- 35.1%, respectively
      (P = .20 and P = .40). CONCLUSION: Extension of embolization to segment IV portal
      branches should not be routinely used because a similar volume increase of
      segments II-III can be simply achieved by right PVE.

PMID- 16301449
TI  - Autoimmune pancreatitis: unveiling a hidden entity.
AB  - HYPOTHESIS: After alcohol-induced and hereditary disease, idiopathic chronic
      pancreatitis is the most common cause of calcifying pancreatitis. This
      designation is used when no associated cause of chronic pancreatitis is found. We
      present 6 cases of idiopathic pancreatitis in which the postoperative
      pathological examination results demonstrated lymphoplasmacytic sclerosing
      pancreatitis or autoimmune pancreatitis. DESIGN: Retrospective case series. The
      medical records of 6 patients referred and treated for autoimmune pancreatitis
      were reviewed. The duration of follow-up varies, the longest being 5 years. The
      disease and a literature review are reported. SETTING: A 200-bed community
      hospital located in a large city. The patients were referred after being treated
      elsewhere for recurrent pancreatitis. PATIENTS AND METHODS: Six patients with
      chronic recurrent pancreatitis were evaluated. They were selected because
      pathological review indicated that they all had autoimmune pancreatitis. RESULTS:
      Six cases of lymphoplasmacytic sclerosing pancreatitis are presented and suggest
      that lymphoplasmacytic sclerosing pancreatitis should be thought of more often in
      chronic autoimmune pancreatitis. CONCLUSION: Lymphoplasmacytic sclerosing
      pancreatitis is an increasingly recognized cause of chronic pancreatitis and
      should be considered in the evaluation of patients with chronic pancreatitis and
      no discernible cause.

PMID- 16301450
TI  - Surgery for gastric cancer combined with cardiac and aortic surgery.
AB  - HYPOTHESIS: Therapeutic strategies for patients who require procedures for both
      cardiac or aortic diseases and gastric cancer are controversial. Prognostic
      factors for them should be clearly identified. DESIGN: Retrospective review of 14
      patients who underwent surgical intervention for both gastric cancer and cardiac
      or aortic diseases between January 1, 2000, and June 30, 2004. SETTING: Tertiary
      referral university hospital. PATIENTS: Cardiac and aortic diseases included
      coronary artery disease in 5 patients, thoracic aortic aneurysms in 3 patients,
      and abdominal aortic aneurysms in 6 patients. Coronary artery bypass graftings
      were performed with an off-pump procedure, and aneurysms were replaced with
      prosthetic grafts in all of the cases. The surgical stages of gastric cancers
      were stage I in 8 patients, stage II in 2 patients, stage III in 3 patients, and
      stage IV in 1 patient. According to our original therapeutic strategies, 4
      patients underwent simultaneous procedures and 10 received staged procedures.
      MAIN OUTCOME MEASURE: Overall survival rates. RESULTS: There was 1 hospital death
      caused by multiple organ failure. No prosthetic graft infection was noted.
      Thirteen patients were discharged, and 3 died of cancer recurrence during an
      average follow-up period of 26.3 months. The cumulative survival rate was 76.6%
      at 1 year and 68.1% at 3 years. One-year survival rates were 90.0% in stages I
      and II gastric cancer and 50.0% in stages III and IV gastric cancer. CONCLUSION:
      Prognosis of patients who underwent surgical intervention for both gastric cancer
      and cardiac or aortic diseases was mainly limited by the clinical stage of
      gastric cancer.

PMID- 16301451
TI  - Predictors of outcome after hyperthermic isolated limb perfusion: role of tumor
      response.
AB  - HYPOTHESIS: Analysis of multiple clinical and pathological factors in patients
      undergoing therapeutic hyperthermic isolated limb perfusion for extremity
      melanoma can identify variables with prognostic significance. DESIGN:
      Retrospective review of a prospectively collected limb perfusion database with a
      median follow-up interval of 32.2 months. SETTING: Single-institution tertiary
      care surgical oncology unit. PATIENTS: We report a series of 59 consecutive
      therapeutic hyperthermic isolated limb perfusion treatments (14 upper extremity
      and 45 lower extremity) in 54 patients with melanoma from January 1, 1995,
      through December 31, 2002, using a standard melphalan dosing protocol. At the
      time of perfusion, 31 cases had fewer than 10 lesions, with none greater than 3
      cm in diameter. The remaining 28 cases had 10 or more lesions or at least 1
      lesion greater than 3 cm in diameter. MAIN OUTCOME MEASURES: Response,
      recurrence, and survival were assessed in relation to multiple demographic,
      clinical, and technical variables using chi2, log-rank, and Kaplan-Meier survival
      analyses. RESULTS: The 3-year survival for the entire cohort was 54%. Thirty
      three (56%) of the 59 perfusion treatments resulted in a persistent complete
      response of at least 6 months' duration. Statistical analysis showed that
      patients with no evidence of regional nodal involvement had a significantly lower
      incidence of distant recurrence (P = .02). Those patients achieving a complete
      response to therapy had a survival advantage (P = .03). CONCLUSION: In patients
      undergoing therapeutic hyperthermic isolated limb perfusion for in-transit
      melanoma, the ability to achieve a complete response following treatment,
      independent of regional nodal status, was the strongest predictor of long-term
      survival.

PMID- 16301452
TI  - Image of the month. Littoral cell angioma.

PMID- 16301453
TI  - Effect of obesity on mortality in severely injured blunt trauma patients remains
      unclear.

PMID- 16301454
TI  - Are young surgeons incompetent?

PMID- 16301455
TI  - Permanent injectables for soft tissue augmentation: avoiding misinformation and a
      reprise of the breast implant debacle.

PMID- 16301456
TI  - Nasal tip overprojection: algorithm of surgical deprojection techniques and
      introduction of medial crural overlay.
AB  - OBJECTIVES: To discuss the evaluation of the overprojected nasal tip, present an
      algorithm of various treatments for deprojection of the nasal tip, and introduce
      our experience of greater than 10 years with medial crural overlay. DESIGN:
      Retrospective review of a large sequential series of patients undergoing
      rhinoplasty who were treated with various deprojection techniques by the senior
      author (R.W.H.K.) from January 1, 1991, through December 31, 2002. Patients
      underwent preoperative and postoperative evaluation during this period on a
      regular basis to record the effects of various approaches on nasal projection,
      rotation, need for revision, and patient satisfaction. Medical records and
      photographic documentation were reviewed. The occurrence of postoperative
      complications and secondary revision procedures were noted. We used the
      information obtained to evaluate and expound on an algorithmic paradigm for
      treatment of nasal tip overprojection. RESULTS: From 1991 to 2002, 130 cases used
      1 or more of the senior author's preferred methods for deprojection. Ten patients
      were excluded owing to the primarily reconstructive nature of their surgery. Of
      the remaining 120 patients, 3 (2.5%) underwent minor revision of dorsal
      irregularities and another 5 (4.2%) underwent tip revision. Only 9 patients
      (7.5%) required concomitant alar base reduction. One patient had postoperative
      epistaxis, and there were no cases of postoperative functional complaints.
      CONCLUSIONS: Deprojection of the overprojected nasal tip can be accomplished
      successfully with a handful of properly used techniques. Once proper analysis has
      been accomplished, an algorithm can be used to help simplify the approach to
      deprojection. These techniques offer sound functional approaches to effect
      deprojection while controlling the level of rotation. The beneficial effects
      observed using this algorithm are attested to by the minimal number of
      complications, the relatively low number of patients requiring revision, and the
      overall long-term patient satisfaction with their results.

PMID- 16301457
TI  - Postoperative management of nasal vestibular stenosis: the custom-made vestibular
      device.
AB  - OBJECTIVE: To evaluate the effect of a custom-made postoperative vestibular
      device on the occurrence and severity of restenosis. DESIGN: This was a
      retrospective study conducted at the Department of Otorhinolaryngology/Head and
      Neck Surgery, Center for Facial Plastic and Reconstructive Surgery of the
      Academic Medical Center. In this tertiary care center between January 1994 and
      December 2000, 52 patients treated for nasal vestibular stenosis received a
      vestibular device directly postoperatively, with the intention to decrease the
      risk of restenosis. The vestibular device was composed of thermoplastic acrylic
      material and had a lumen to facilitate breathing. The shape of the device was
      custom-made within 1 week after surgery and was subsequently worn by the patient
      for 12 weeks (6 weeks continuously and 6 weeks only during the night). After this
      period, the occurrence and severity of restenosis of the nasal vestibule were
      evaluated and the necessity for a potential adjuvant operation was assessed.
      RESULTS: Preoperatively, of the 52 patients, 38 (73%) had severe stenosis, 13
      (25%) had moderate stenosis, and 1 (2%) had mild stenosis. Postoperatively, 15
      (29%) of the patients had mild restenosis, 1 had a case of moderate stenosis, and
      1 had a case of severe stenosis. Only the latter patient required a subsequent
      revision. Functional improvement was noticed in 51 (98%) of the patients, whereas
      49 (94%) of the patients showed aesthetic improvement after the initial
      procedure. CONCLUSIONS: In case of surgical treatment of vestibular stenosis, the
      use of a custom-made vestibular device may help prevent restenosis. In addition
      to functional improvement, the device may also improve the aesthetic result. The
      device does not seem to have any negative adverse effects, was easy to make, and
      was comfortable for the patient to wear.

PMID- 16301458
TI  - Use of precontoured positioning plates and pericranial flaps in midfacial
      reconstruction to optimize aesthetic and functional outcomes.
AB  - OBJECTIVES: To present our experience with reconstruction of midfacial defects
      using "precontoured positioning plates" with or without pericranial flaps and to
      describe our technique in detail. METHODS: Thirty-two consecutive patients with
      midfacial defects subsequent to oncologic resection that were reconstructed
      primarily with cranial bone grafts and precontoured positioning plates were
      reviewed for type of defect, functional outcome, complications, and postoperative
      appearance. RESULTS: Primary reconstruction of all defects in this series was
      performed. Defects involved the orbital rim, orbital floor, or both in 28
      patients (88%), the body of the zygoma in 24 patients (75%), and extended to the
      skull base in 16 patients (50%). Pericranial flaps were used to cover the bone
      grafts in 22 patients (69%). Postoperative radiotherapy was performed in 22
      patients (69%), preoperative radiotherapy in 5 (16%), and the other 5 (16%) had
      no radiotherapy. There were no intraoperative complications, and postoperative
      complications included plate exposure (n = 2), ectropion (n = 3), and partial
      bone graft loss or resorption subsequent to completion of radiotherapy (n = 2).
      Postoperatively, appearance was excellent in 24 patients, fair in 6 patients, and
      poor in 2 patients. Secondary reconstructive procedures were performed in 4
      patients (12%). Follow-up ranged from 12 months to 6 years (median, 4.2 years).
      CONCLUSIONS: Precontoured positioning plates with or without pericranial flaps
      enable precise reconstruction of midfacial defects with precise incorporation of
      cranial bone grafts. In our series we routinely covered the bone grafts with well
      vascularized tissues, leading to a low incidence of complications and excellent
      aesthetic results.

PMID- 16301459
TI  - Use of BioGlue surgical adhesive for brow fixation in endoscopic browplasty.
AB  - OBJECTIVE: To determine the efficacy, longevity, and safety of BioGlue Surgical
      Adhesive for periosteal fixation in endoscopic browlifts. METHODS: Retrospective
      review of 80 patients who underwent endoscopic browlift using BioGlue as the
      primary means of periosteal fixation. Visits were categorized as preoperative, 1
      to 2 months, 3 to 6 months, and 7 to 12 months, and photographs of the first 15
      patients were evaluated for change in brow position at each of these visits. Brow
      position was measured at the lowest brow hairs at the midpupillary and lateral
      canthus positions. Follow-up was 3 months to 3 years. RESULTS: All of the first
      15 patients were included in the 1- to 2-month postoperative grouping, 13 in the
      3- to 6-month grouping, and 10 in the 7- to 12-month grouping. At all
      postoperative visits, brow elevation was significantly maintained during 12-month
      follow-up. Revision has been required in only 1 of 80 patients to date.
      CONCLUSIONS: BioGlue is an effective and safe method of maintaining brow position
      in endoscopic browplasty. Brow elevation achieved using BioGlue was significantly
      maintained during the 7- to 12-month postoperative period. Tissue adhesives such
      as BioGlue have the potential to become significant adjuncts in facial plastic
      surgery and warrant more critical evaluation.

PMID- 16301460
TI  - Distraction osteogenesis for cleft palate closure in a canine model.
AB  - OBJECTIVE: To assess the utility of distraction osteogenesis (DO) when applied to
      closure of a hard palate cleft in dogs. METHODS: A midline hard palate cleft was
      created in 10 mature dogs. Two were controls and had no distraction; the other 8
      dogs underwent osteotomies with installation of customized DO devices to the hard
      palate. After a 10-day latency, distraction commenced at 1 mm/d. After a 14-day
      consolidation period, the device was removed and the mucosa closed. Each dog was
      injected with fluorochrome labels and serially killed at 2-week intervals. Bone
      healing was analyzed further with traditional histologic analysis and
      fluorochrome labeling. RESULTS: No serious complications occurred. Bone
      resorption and cleft widening occurred in both control dogs. Complete bone
      closure of the hard palate cleft was achieved with DO in 5 of 8 experimental
      dogs. Three experimental dogs had bone resorption and incomplete palatal closure.
      CONCLUSIONS: The application of DO techniques in closure of a hard palate cleft
      in a canine model is safe and well tolerated. Furthermore, in some cases, it
      proved effective in achieving bony closure of the cleft. Further investigation is
      warranted into innovative use of DO in treating children born with cleft palate.

PMID- 16301461
TI  - Limitations of distraction osteogenesis in children.

PMID- 16301462
TI  - Viability of cultured human nasal septum chondrocytes after crushing.
AB  - OBJECTIVE: To investigate how different degrees of crushing affect the viability
      of human nasal septum chondrocytes in adherent cell cultures. METHODS: Cartilage
      grafts were harvested from the nasal septa of 15 patients who underwent
      submucosal resection. Five cartilage pieces were prepared from each specimen as
      follows: the cartilage was left intact, slightly crushed, moderately crushed,
      significantly crushed, or severely crushed. Chondrocytes were isolated for trypan
      blue dye exclusion testing, and the numbers of viable cells were determined at 1,
      2, 3, and 10 days after culturing. Comparisons were made among the groups.
      RESULTS: The day 1 viability rates for the intact, slightly crushed, moderately
      crushed, significantly crushed, and severely crushed cartilage preparations were
      96%, 92%, 82%, 72%, and 54%, respectively. The corresponding rates on day 10 were
      93%, 90%, 84%, 75%, and 68%. CONCLUSIONS: The viability and proliferative
      capacity of crushed human septal cartilage depend on the degree of crushing
      sustained. Slightly or moderately crushed cartilage grafts show good chondrocyte
      viability and proliferation and are valuable for fashioning soft nasal contours,
      filling defects, and concealing dorsal irregularities. However, significant or
      severe crushing reduces chondrocyte viability and proliferation and may result in
      unpredictable degrees of graft volume loss.

PMID- 16301463
TI  - Powered endoscopic septoplasty for septal deviation and isolated spurs.
AB  - Septoplasty is commonly performed for nasal airway obstruction or rhinologic
      headache due to contact irritation, often in conjunction with other nasal
      procedures, including cosmetic rhinoplasty and endoscopic sinus
      surgery.Traditionally, it is performed before these procedures via a "headlight"
      technique. This article describes the use of the microdebrider in 29 cases of
      endoscopic septoplasty. Many of the procedures were performed in conjunction with
      functional endoscopic sinus surgery; however, several were performed as an
      isolated procedure or with inferior turbinoplasty. The technique is described in
      detail. All 29 patients had significant improvement in their symptoms, and no
      patient developed a perforation or postoperative hematoma. Conversion to a
      traditional septoplasty was required in 1 case because of the severity of the
      deviation. Power-assisted endoscopic septoplasty is a useful adjunct in cases
      involving isolated septal spurs or moderate septal deviations. Patients with
      severe nasal obstruction due to caudal deflection of the septum off the nasal
      spine are better served with traditional headlight septoplasty.

PMID- 16301464
TI  - Technical advances in nasal surgery.

PMID- 16301465
TI  - Interlocked transdomal suture technique for the wide interdomal space in
      rhinoplasty.

PMID- 16301466
TI  - Postauricular transposition flap for cutaneous auricular defects.

PMID- 16301468
TI  - Straightening the crooked middle third of the nose: use of high-density porous
      polyethylene extended spreader grafts.

PMID- 16301469
TI  - Hospital transfer and death resulting from in-office surgical procedures:
      vigilance still required.

PMID- 16301470
TI  - The importance of good outcomes data in studies of nasal and sinus surgery.

PMID- 16301473
TI  - Beyond social awkwardness: problems with "reading" faces?

PMID- 16301474
TI  - Clinical findings of the phakomatoses: tuberous sclerosis.

PMID- 16301475
TI  - Molecular types of Creutzfeldt-Jakob disease: the strange diversity of prions.

PMID- 16301476
TI  - When should we warn the surgeon? Diagnosis-based warning criteria for BAEP
      monitoring.

PMID- 16301477
TI  - Diffusion MRI in multiple sclerosis.
AB  - Diffusion imaging is a quantitative, MR-based technique potentially useful for
      the study of multiple sclerosis (MS), due to its increased pathologic specificity
      over conventional MRI and its ability to assess in vivo the presence of tissue
      damage occurring outside T2-visible lesions, i.e., in the so-called normal
      appearing white and gray matter. The present review aims at critically
      summarizing the state-of-the-art and providing a background for the planning of
      future diffusion studies of MS. Several pieces of evidence suggest that diffusion
      weighted and diffusion tensor MRI are sensitive to MS damage and able to detect
      its evolution over relatively short periods of time. Although a significant
      relationship between diffusion-weighted MRI findings and MS clinical disability
      was not found in the earliest studies, with improved diffusion imaging technology
      correlations between diffusion abnormalities and MS clinical aspects are now
      emerging. However, the best acquisition and postprocessing strategies for MS
      studies remain a matter of debate and the contribution of newer and more
      sophisticated techniques to diffusion tensor MRI investigations in MS needs to be
      further evaluated. Although changes in diffusion MRI indices reflect a net loss
      of structural organization, at present we can only speculate on their possible
      pathologic substrates in the MS brain. Postmortem studies correlating diffusion
      findings with histopathology of patients with MS are, therefore, also warranted.

PMID- 16301478
TI  - Blood pressure recovery from Valsalva maneuver in patients with autonomic
      failure.
AB  - BACKGROUND: Blood pressure (BP) changes in response to the Valsalva maneuver (VM)
      reflect the integrity of the baroreflex that regulates BP, and the phases of VM
      are widely used indices of adrenergic evaluation. OBJECTIVE: To study the BP
      recovery time (PRT) following termination of VM back to baseline to determine if
      it could be an additional and better indicator of adrenergic function. METHODS:
      The authors evaluated three groups of patients with increasing degrees of
      adrenergic failure and an age-matched control group. Adrenergic failure was
      graded on the basis of systolic blood pressure (SBP) reduction to tilt: Group 1,
      orthostatic hypotension (OH; SBP > or = 30 mm Hg); Group 2, borderline OH (BOH;
      30 > SBP > 10 mm Hg); and Group 3, sympathetic sudomotor failure. RESULTS: PRT
      was found to vary directly with severity of adrenergic impairment. PRT
      significantly correlated with previously utilized phases of the VM and baroreflex
      gain, with highest correlations with phases II_L (reflex vasoconstriction
      following initial fall in BP) and IV (BP overshoot following the VM). PRT extends
      the indices for the quantitation of adrenergic failure, since it will continue to
      parallel increasing adrenergic failure after phase II_L is lost and is a reliable
      index when II_L cannot be recorded. CONCLUSIONS: Pressure recovery time is a
      valuable index of adrenergic failure. It extends the value of the Valsalva
      maneuver by providing a quantitative index that is measurable in patients with
      severe adrenergic failure.

PMID- 16301479
TI  - Neuronal intranuclear hyaline inclusion disease showing motor-sensory and
      autonomic neuropathy.
AB  - BACKGROUND: Neuronal intranuclear hyaline inclusion disease (NIHID), a rare
      neurodegenerative disease in which eosinophilic intranuclear inclusions develop
      mainly in neurons, has not yet been described to present as hereditary motor
      sensory and autonomic neuropathy. METHODS: Patients in two NIHID families showing
      peripheral neuropathy were evaluated clinically, electrophysiologically, and
      histopathologically. RESULTS: In both families, patients had severe muscle
      atrophy and weakness in limbs, limb girdle, and face; sensory impairment in the
      distal limbs; dysphagia, episodic intestinal pseudoobstruction with vomiting
      attacks; and urinary and fecal incontinence. No patients developed symptoms
      suggesting CNS involvement. Electrophysiologic study showed the reduced motor and
      sensory nerve conduction velocities and amplitudes, and also extensive
      denervation potentials. In sural nerve specimens, numbers of myelinated and
      unmyelinated fibers were decreased. In two autopsy cases, eosinophilic
      intranuclear inclusions were widespread, particularly in sympathetic and
      myenteric ganglion neurons, dorsal root ganglion neurons, and spinal motor
      neurons. These neurons also were decreased in number. CONCLUSION: Patients with
      neuronal intranuclear hyaline inclusion disease (NIHID) can manifest symptoms
      limited to those of peripheral neuropathy. NIHID therefore is part of the
      differential diagnosis of hereditary motor-sensory neuropathy associated with
      autonomic symptoms. Intranuclear hyaline inclusions in Schwann cells and in the
      myenteric plexus may permit antemortem diagnosis of NIHID.

PMID- 16301480
TI  - Brainstem auditory evoked potential monitoring: when is change in wave V
      significant?
AB  - BACKGROUND: The probability of hearing loss during cerebellopontine angle (CPA)
      surgery can be reduced by using brainstem auditory evoked potential (BAEP)
      intraoperative monitoring (IOM). A wave V latency prolongation of 1.0
      milliseconds or amplitude decrement of greater than 50% is arbitrarily considered
      the point when damage to hearing occurs. OBJECTIVE: To determine the accuracy of
      wave V changes in predicting hearing impairment. METHODS: Patients undergoing
      BAEP IOM for surgery in the CPA region were evaluated. The greatest wave V
      latency and amplitude change was determined. Patients were divided into four
      groups depending on degree of change of wave V: Group 1 consisted of minimal
      change, whereas Group 4 was permanent loss of wave V. The frequency of hearing
      loss in each group was compared. RESULTS: Data from 156 patients were reviewed.
      When all patients were analyzed, the frequency of hearing loss was not
      significantly different between the groups. When patients with CPA tumor were
      excluded, a significantly higher number of patients in Group 4 had hearing loss.
      Analysis of the patients with CPA tumor showed no difference in the frequency of
      hearing loss in any of the groups; even a large number (50%) of Group 1 patients
      had hearing impairment. CONCLUSIONS: During brainstem auditory evoked potential
      intraoperative monitoring, the type of surgery is important when interpreting
      significance of changes of wave V. For non-cerebellopontine angle tumor surgery,
      hearing loss occurs usually only with permanent loss of wave V; much smaller
      changes may be important in cerebellopontine angle tumor surgery.

PMID- 16301481
TI  - Chronic migraine is an earlier stage of transformed migraine in adults.
AB  - BACKGROUND: Chronic migraine (CM) is characterized by 15 or more migraine days
      per month. Most adults with chronic daily headache (CDH) that evolved from
      migraine have < 15 days of migraine/month. They are often classified as
      transformed migraine (TM), a disorder not addressed in the International Headache
      Society classification. OBJECTIVE: To test the hypothesis that early in the
      course of migraine chronification, the frequency of migraine attacks is high and
      that as illness progresses the frequency of nonmigraine headaches increases.
      METHODS: Information was collected on 402 adults with TM and was divided into two
      groups. Group 1 TM had > or = 15 days of migraine/month, whereas Group 2 TM had <
      15 days of migraine/month. Risk factors were modeled for number of migraine days
      per month using logistic regression. RESULTS: Of 402 subjects with TM, 121
      (30.1%) were in Group 1. The proportion of Group 1 subjects decreased with age,
      from 71% below age 30 to 22% age 60 or above. The correspondent proportion of
      Group 2 increased from 29 to 78%. More than 15 days of migraine per month was
      independently predicted by younger ages (< 40 years; p = 0.002), shorter interval
      from episodic to CDH (< 5 years; p = 0.003), and shorter time since the
      development of CDH (< 6 years; p < 0.0001). CONCLUSION: Chronic migraine is an
      earlier stage of transformed migraine.

PMID- 16301482
TI  - "Silent event-related" fMRI reveals reduced sensorimotor activation in laryngeal
      dystonia.
AB  - OBJECTIVE: To study with fMRI the pattern of sensorimotor activation in patients
      with spasmodic dysphonia (laryngeal dystonia) compared to healthy controls.
      METHODS: The authors performed fMRI measurements during vocal motor tasks in 12
      patients with laryngeal dystonia and compared them with those of 12 healthy
      volunteers. Patients were scanned before (pre) and after (post) treatment with
      local injections of botulinum toxin (BTX). They examined two different motor
      tasks: simple vocalization inducing dystonia and whispering without appearance of
      dystonic symptoms. To avoid movement artifacts with oral motor tasks, the authors
      used a silent event-related fMRI approach involving noncontinuous sampling with
      no data acquisition during task performance. RESULTS: They found reduced
      activation of primary sensorimotor as well as of premotor and sensory association
      cortices during vocalization in patients with laryngeal dystonia pre-BTX. This
      was partly observed also during the asymptomatic whispering task. BTX treatment
      did not result in reversal of reduced cortical activation. CONCLUSION: fMRI
      signal is reduced in sensorimotor cortices associated with movement of the
      affected body part in laryngeal dystonia, supporting a dystonic basis for this
      voice disorder.

PMID- 16301483
TI  - Factors influencing susceptibility to compulsive dopaminergic drug use in
      Parkinson disease.
AB  - BACKGROUND: In the course of treatment, a small group of patients with Parkinson
      disease (PD) develop a harmful pattern of compulsive dopaminergic drug use,
      called the dopamine dysregulation syndrome (DDS). Individual factors may
      influence susceptibility. OBJECTIVES: To identify predisposing factors to DDS in
      a population of outpatients with PD. METHODS: The authors compared clinical
      features, impulsive sensation seeking (ISS) personality traits, past experimental
      drug use, alcohol consumption, smoking behaviors, and depressive symptoms in 25
      patients with DDS to an outpatient sample of 100 patients with PD who were not
      compulsively overusing dopaminergic medication. RESULTS: Patients with DDS had a
      significantly younger age at disease onset, higher dopaminergic drug intake,
      greater past experimental drug use, more depressive symptoms, scored higher on
      ISS ratings, and tended to have higher alcohol intake. Using logistic regression
      analysis, we found that novelty seeking personality traits, depressive symptoms,
      alcohol intake, and age at PD onset were significant predictors of DDS.
      CONCLUSIONS: These factors may help to identify early patients who are more
      vulnerable to developing a pattern of compulsive dopaminergic drug use and help
      minimize its consequences.

PMID- 16301484
TI  - Education and occupations preceding Parkinson disease: a population-based case
      control study.
AB  - OBJECTIVE: To investigate the association of Parkinson disease (PD) with
      education and occupations using a case-control study design. METHODS: The authors
      used the medical records-linkage system of the Rochester Epidemiology Project to
      identify all subjects who developed PD in Olmsted County, MN, from 1976 through
      1995. Each incident case was matched by age (+/-1 year) and sex to a general
      population control. The authors collected information about education and
      occupations using two independent sources of data: a review of the complete
      medical records in the system and a telephone interview. Occupations were coded
      using the 1980 Standard Occupational Classification. RESULTS: Subjects with 9 or
      more years of education were at increased risk of PD (OR = 2.0; 95% CI = 1.1 to
      3.6; p = 0.02), and there was a trend of increasing risk with increasing
      education (test for linear trend, p = 0.02; medical records data). Physicians
      were at significantly increased risk of PD using both sources of occupational
      data. By contrast, four occupational groups showed a significantly decreased risk
      of PD using one source of data: construction and extractive workers (e.g.,
      miners, oil well drillers), production workers (e.g., machine operators,
      fabricators), metal workers, and engineers. These associations with increased or
      decreased risk did not change noticeably after adjustment for education.
      CONCLUSION: Subjects with higher education and physicians have an increased risk
      of Parkinson disease (PD), while subjects with some occupations presumed to
      involve high physical activity have a decreased risk of PD.

PMID- 16301485
TI  - Damage within a network of white matter regions underlies executive dysfunction
      in CADASIL.
AB  - OBJECTIVE: To identify the important sites of white matter disruption that
      underpin executive dysfunction in CADASIL (cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy), a genetic model
      of pure subcortical vascular disease. METHODS: The anatomic pattern of
      correlation between tissue integrity and executive function was explored with
      diffusion tensor imaging (DTI), which provides quantitative measures of tissue
      integrity. Eighteen nondemented patients with CADASIL underwent DTI and cognitive
      assessment. DTI was normalized to a standard template and correlations assessed
      at every voxel across the brain with Statistical Parametric Mapping with cluster
      level correction for multiple comparisons. RESULTS: For executive tasks,
      correlations were found in a number of discrete regions in the white matter of
      the frontal lobes. A distinct, nonoverlapping pattern of correlation was seen for
      verbal memory. Significant independent correlations remained in some regions
      after co-varying for age and IQ. CONCLUSIONS: Different cognitive functions
      correlate with structural integrity at different sites in the white and
      subcortical gray matter. The distribution of regions correlating specifically
      with executive function provides clues to the organization of the relevant
      cognitive networks and their important white matter projections. The cingulum
      bundle is one candidate tract that may carry anteroposterior connections
      important for executive processes.

PMID- 16301486
TI  - A room from Jean-Martin Charcot's house at the Metropolitan Museum of Art.

PMID- 16301488
TI  - Diabetes and cognitive function in a middle-aged cohort: findings from the
      Whitehall II study.
AB  - OBJECTIVE: To compare cognitive performance in those with diabetes, impaired
      glucose tolerance, and normoglycemia in a middle-aged cohort. METHODS: The
      authors analyzed data from a prospective occupational cohort study begun in 1985
      1988 (baseline). Diabetes was classified from oral glucose tolerance tests that
      were performed in 1992-1993 (phase 3) and 1997-1999 (phase 5) and self reported
      diagnosis of diabetes from questionnaire at baseline, 1989 (phase 2), phase 3,
      1995 (phase 4), and phase 5 of the study. A battery of cognitive tests (memory,
      Alice Heim 4 [AH 4], Mill Hill vocabulary test, phonemic fluency, and categorical
      fluency) were measured at phase 5 in 4,020 men and 1,627 women with a mean age of
      56 and free of symptoms of stroke. RESULTS: At phase 5, a total of 208 (5%) men
      and 101 (6%) women had diabetes while 405 (10%) men and 192 (12%) women had
      impaired glucose tolerance. Those with diabetes were at increased risk of poor
      performance in AH 4 compared to those without (men: OR, 2.45; 95% CI, 1.77 to
      3.38; women: OR, 1.83; 95% CI, 1.09 to 3.08). These effects were independent of
      age, social position, vascular problems, and health-related behaviors. Impaired
      glucose tolerance was not related to any measure of cognition. CONCLUSIONS: Type
      2 diabetes is associated with poor performance in some aspects of cognition in
      middle-aged men and women.

PMID- 16301487
TI  - Association of sex steroid hormones with brain morphology and cognition in
      healthy elderly men.
AB  - BACKGROUND: There is inconsistent evidence of the presence and direction of the
      relationship between sex hormone concentrations and cognitive function in older
      men, and there is little published literature on the relationship of sex hormone
      concentrations and brain volume as measured by MRI. OBJECTIVE: To examine the
      hypothesis that midlife total serum concentrations of testosterone (T),
      estradiol, estrone, and sex hormone binding globulin (SHBG) predict cognitive
      task performance and regional brain volumes at 10- to 16-year follow-up, in a
      longitudinal sample of World War II veteran twin men. METHODS: Treating twins as
      individuals, linear regression models were used, adjusting analyses for age,
      education, depressive symptomatology, blood pressure, alcohol consumption, years
      of cigarette smoking, and APOE epsilon4 allele status. RESULTS: There were no
      significant associations between sex hormone or SHBG concentrations and
      performance on a series of cognitive tasks measuring global and executive
      function, visual and verbal learning and memory. Higher midlife T concentrations
      were associated with larger hemispheric, frontal, and parietal regional brain
      volumes and with smaller left occipital brain volume. Higher estradiol and
      estrone concentrations were also associated with smaller right (estradiol) and
      both right and left (estrone) occipital volumes, but with no other brain regions.
      Owing to the multiple comparisons conducted, some significant associations may
      have occurred by chance. CONCLUSIONS: Overall, the pattern of results suggests a
      role for sex hormones in brain volume that predates potentially observable
      associations between sex hormones and cognitive task performance.

PMID- 16301489
TI  - Seizure focus affects regional language networks assessed by fMRI.
AB  - OBJECTIVE: To investigate the degree of language dominance in patients with left
      and right hemisphere seizure foci compared to normal volunteers using a fMRI
      reading comprehension task. METHODS: Fifty patients with complex partial
      epilepsy, aged 8 to 56 years and 33 normal volunteers, aged 7 to 34 had fMRI (1.5
      T) and neuropsychological testing. Participants silently named an object
      described by a sentence compared to a visual control. Data were analyzed with
      region of interest (ROI) analysis based on t maps for inferior frontal gyrus
      (IFG), midfrontal gyrus (MFG), and Wernicke area (WA). Regional asymmetry indices
      (AIs) were calculated [(L - R)/(L + R)]; AI > 0.20 was deemed left dominant and
      AI < 0.20 as atypical language. RESULTS: Left hemisphere focus patients had a
      higher likelihood of atypical language than right hemisphere focus patients (21%
      vs 0%, chi2 < 0.002). Left hemisphere focus patients, excluding those with
      atypical language, had lower regional AI in IFG, MFG, and WA than controls. Right
      hemisphere focus patients were all left language dominant and had a lower AI than
      controls in WA and MFG, but not for IFG. AI in MFG and WA were similar between
      left hemisphere focus/left language patients and right hemisphere focus patients.
      Patients activated more voxels than healthy volunteers. Lower AIs were
      attributable to greater activation in right homologous regions. Less activation
      in the right-side WA correlated with better verbal memory performance in right
      focus/left hemisphere-dominant patients, whereas less strongly lateralized
      activation in IFG correlated better with Verbal IQ in left focus/left hemisphere
      dominant patients. CONCLUSIONS: Patients had lower asymmetry indices than healthy
      controls, reflecting increased recruitment of homologous right hemisphere areas
      for language processing. Greater right hemisphere activation may reflect greater
      cognitive effort in patient populations, the effect of epilepsy, or its
      treatment. Regional activation patterns reflect adaptive efforts at recruiting
      more widespread language processing networks that are differentially affected
      based on hemisphere of seizure focus.

PMID- 16301490
TI  - Dystonic posturing in seizures of mesial temporal origin: electroclinical and
      metabolic patterns.
AB  - OBJECTIVE: To test the hypothesis that extratemporal neuronal networks are
      involved in dystonic posturing (DP) observed in mesial temporal epilepsy (MTLE).
      METHODS: The authors analyzed electroclinical findings in 36 patients with MTLE
      with or without DP. Three DP types were defined (types I, II, III) corresponding
      to a gradual increase in duration and complexity. Interictal
      [18F]fluorodeoxyglucose-PET in different groups and subgroups was compared with
      control subjects using statistical parametric mapping software (SPM99). RESULTS:
      DP was found in 20 patients (55%), contralateral to the epileptogenic focus in
      95%. Patients with DP had longer seizure duration, higher frequency of head
      deviation, salivation, motor manifestations, secondary generalization, severe
      clouding of consciousness, and prolonged postictal confusion when compared with
      patients without DP. Ictal discharge patterns during DP consisted of fast
      rhythmic activity spreading to frontal or suprasylvian areas, whereas slow
      rhythmic activity restricted to the temporal areas occurred in the absence of DP.
      In patients with DP, widespread temporal and extratemporal hypometabolism
      including the putamen was found. Hypometabolism was restricted to the
      anteromesial part of the temporal lobe and anterior insula in patients without
      DP. Putaminal hypometabolism was found in all DP types, but different
      extratemporal cortical involvements were found in DP subgroups: insula and
      inferior frontal gyrus in type I, inferior and superior frontal gyri and anterior
      cingulate gyrus in type II, and parietal areas in type III. CONCLUSION: Dystonic
      posturing may result from involvement of both putaminal and extratemporal
      cortical areas. Moreover, different frontal or parietal networks may be involved
      according to the duration or complexity of dystonic posturing.

PMID- 16301491
TI  - Perception of facial expression and facial identity in subjects with social
      developmental disorders.
AB  - BACKGROUND: It has been hypothesized that the social dysfunction in social
      developmental disorders (SDDs), such as autism, Asperger disorder, and the
      socioemotional processing disorder, impairs the acquisition of normal face
      processing skills. The authors investigated whether this purported perceptual
      deficit was generalized to both facial expression and facial identity or whether
      these different types of facial perception were dissociated in SDDs. METHODS:
      They studied 26 adults with a variety of SDD diagnoses, assessing their ability
      to discriminate famous from anonymous faces, their perception of emotional
      expression from facial and nonfacial cues, and the relationship between these
      abilities. They also compared the performance of two defined subgroups of
      subjects with SDDs on expression analysis: one with normal and one with impaired
      recognition of facial identity. RESULTS: While perception of facial expression
      was related to the perception of nonfacial expression, the perception of facial
      identity was not related to either facial or nonfacial expression. Likewise,
      subjects with SDDs with impaired facial identity processing perceived facial
      expression as well as those with normal facial identity processing. CONCLUSION:
      The processing of facial identity and that of facial expression are dissociable
      in social developmental disorders. Deficits in perceiving facial expression may
      be related to emotional processing more than face processing. Dissociations
      between the perception of facial identity and facial emotion are consistent with
      current cognitive models of face processing. The results argue against hypotheses
      that the social dysfunction in social developmental disorder causes a generalized
      failure to acquire face-processing skills.

PMID- 16301492
TI  - Axonal injury in early multiple sclerosis is irreversible and independent of the
      short-term disease evolution.
AB  - OBJECTIVE: To define the nature and the temporal evolution of neuronal/axonal
      injury in patients at the earliest clinical stage of multiple sclerosis (MS),
      using whole brain N-acetylaspartate (WBNAA) proton MR spectroscopy (1H-MRS).
      METHODS: Thirty-five patients at presentation with clinically isolated syndromes
      (CIS) and MRI evidence of disease dissemination in space were studied. The
      following scans of the brain were acquired within 3 months from the onset of the
      disease and after 12 months: 1) dual-echo; 2) WBNAA 1H-MRS; 3) pre- and
      postcontrast T1-weighted. The same scans were obtained in 12 age-matched healthy
      subjects, without contrast administration. In patients, conventional MRI scans
      were also repeated 3 months after the first scanning session, to assess the
      presence of early disease dissemination in time (DIT). RESULTS: Over the study
      period, 24 patients showed MRI evidence of disease DIT, thus fulfilling the
      criteria for a diagnosis of MS. The average WBNAA amount was lower in CIS
      patients than in controls both at baseline (13.7 vs 16.9 mM, p < 0.001) and at 1
      year follow-up (12.6 vs 16.2 mM, p < 0.001), but the average yearly percentage
      change of WBNAA did not differ between the two groups. No MRI or 1H-MRS
      quantities were significantly associated with the disease DIT over the study
      period. CONCLUSION: Irreversible brain damage associated with axonal dysfunction
      occurs at a very early stage in patients with clinically isolated syndromes, but
      it does not seem to be related with the disease evolution in the subsequent short
      term period.

PMID- 16301493
TI  - Transmission ratio distortion in the spinal muscular atrophy locus: data from 314
      prenatal tests.
AB  - BACKGROUND: Spinal muscular atrophy (SMA) is a recessive neurodegenerative
      disorder characterized by the loss of alpha-motor neurons in the spinal cord and
      subsequent death of motor neuron cells. SMA occurs with a frequency of 1 in 6,000
      live births, with a carrier frequency of 1 in 40, and is a leading genetic cause
      of infant mortality. SMA is caused by loss or mutation of the telomeric survival
      motor neuron gene (SMN1), which is deleted in almost 94% of SMA patients
      OBJECTIVE: To analyze the transmission ratio at the SMA locus, examining the
      segregation of the SMN1-deleted alleles in 314 fetuses from carrier parents who
      requested prenatal testing for the disease. METHODS: Prenatal diagnosis of SMA in
      families at 25% risk of the disease has been performed on chorionic villous
      sampling specimens, through direct detection of the SMN1 gene mutation and
      linkage analysis using microsatellite markers from the 5q13 region. Analysis of
      the genotypic/allelic frequencies of the SMN1 gene was performed using the chi2
      test, assuming a recessive mendelian inheritance. RESULTS: Of 314 fetuses
      analyzed, 95 were homozygous for the wild-type allele (30.3%), 154 were carriers
      (49.0%), and the remaining 65 were homozygous for the mutated allele (20.7%).
      Statistical analysis demonstrated that proportion of fetuses predicted with SMA
      is lower than 25% expected for a recessive disorder, resulting in a transmission
      rate of the SMN1-deleted allele deviant from the 50% expected in a random the
      segregation of a mendelian tract (p = 0.016) CONCLUSIONS: This is the first study
      to evaluate the genotypic frequencies at the spinal muscular atrophy (SMA) locus
      based on data derived from prenatal analysis, which are not subject to
      ascertainment bias. The analysis showed a transmission ratio distortion at the
      SMA locus in favor of the SMN1 wild-type alleles.

PMID- 16301494
TI  - Similar brain tau pathology in DM2/PROMM and DM1/Steinert disease.
AB  - Neurofibrillary degeneration (NFD) occurs in the brains of patients with myotonic
      dystrophy (DM) type 1. The authors report a similar tau pathology in the CNS of a
      patient with DM2 and compare it to that of patients with DM1. A reduced
      expression of tau exon 2 and exon 3 epitopes is observed in both DM1 and DM2.
      This suggests a similar physiopathologic process that may contribute to common
      neurologic features in patients with DM.

PMID- 16301495
TI  - Multifocal motor sensory demyelinating neuropathy: inflammatory demyelinating
      polyradiculoneuropathy.
AB  - The authors present two cases that provide the first autopsy findings in
      multifocal acquired demyelinating sensory and motor neuropathy (MADSAMN). Both
      cases documented multifocal but asymmetric demyelinating neuropathy with rare
      axonal degeneration. One case clearly documented an inflammatory
      polyradiculoplexoneuropathy, confirming the inflammatory nature of this
      neuropathy. This study showed that MADSAMN is an inflammatory demyelinating
      polyradiculoneuropathy that shares histologic features observed in chronic
      inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy
      (MMN), suggesting a similar immunopathogenesis for these entities.

PMID- 16301496
TI  - Lack of association between VEGF polymorphisms and ALS in a Dutch population.
AB  - Sequence alterations in the promoter region of the vascular endothelial growth
      factor (VEGF) gene have been implicated in increasing the risk of developing ALS.
      VEGF promoter haplotypes were determined in 373 patients with sporadic ALS and
      615 matched healthy controls in The Netherlands. No significant association
      between the previously reported at-risk haplotypes and ALS was found. Pooling our
      results with the previously studied population still showed a significant
      association with the AAG haplotype.

PMID- 16301497
TI  - Significance of phrenic nerve electrophysiological abnormalities in Guillain
      Barre syndrome.
AB  - The authors investigated whether the amplitude and latency of diaphragm compound
      muscle action potential helped predict respiratory failure in Guillain-Barre
      syndrome. Both variables were significantly but weakly correlated with vital
      capacity (VC) and were similar in unventilated (n = 60) and ventilated (n = 10)
      patients. In ventilated patients, motor loss severity, progression, and VC
      reduction were significantly greater, and bulbar dysfunction was more common.
      Predicting respiratory failure must rely on clinical features and VC.

PMID- 16301498
TI  - Tearing without pain after trigeminal root section for cluster headache.
AB  - The cranial autonomic symptoms (CAS) in patients with cluster headache (CH) are
      considered to occur as a result of intense ophthalmic division pain. Five CH
      patients underwent transection of the trigeminal nerve root but continued to
      experience periodic CAS without pain, whereas another five patients continued to
      experience typical cluster headaches. These findings confirm that CH is generated
      by a central pacemaker and the pain may be expressed without activation of the
      peripheral trigeminovascular network.

PMID- 16301499
TI  - Increased frequency of restless legs syndrome in a French-Canadian population
      with multiple sclerosis.
AB  - The authors evaluated the co-occurrence of multiple sclerosis (MS) and restless
      legs syndrome (RLS) using an RLS questionnaire. They evaluated 200 patients with
      MS, 100 with rheumatoid arthritis (RA), and 100 controls, all French-Canadians.
      They found that 37.5% of MS patients, 31% of RA patients, and 16% of controls
      fulfilled the criteria for RLS. MS can cause RLS, or MS and RLS may have common
      susceptibility factors.

PMID- 16301500
TI  - Benefits of rivastigmine on attention in dementia associated with Parkinson
      disease.
AB  - In a 24-week, randomized, double-blind, placebo-controlled, multicenter study of
      rivastigmine, 487 patients with dementia associated with Parkinson disease
      underwent assessment of attention on the Cognitive Drug Research computerized
      cognitive assessment system before dosing and 16 and 24 weeks later. Significant
      benefits of rivastigmine over placebo were seen on all aspects of attention
      assessed: sustained attention, focused attention, consistence of responding, and
      central processing speed.

PMID- 16301501
TI  - H2(15)O or 13NH3 PET and electromagnetic tomography (LORETA) during partial
      status epilepticus.
AB  - The authors evaluated the feasibility and source localization utility of H2(15)O
      or 13NH3 PET and low-resolution electromagnetic tomography (LORETA) in three
      patients with partial status epilepticus (SE). Results were correlated with
      findings from intraoperative electrocorticographic recordings and surgical
      outcomes. PET studies of cerebral blood flow and noninvasive source modeling with
      LORETA using statistical nonparametric mapping provided useful information for
      localizing the ictal activity in patients with partial SE.

PMID- 16301502
TI  - Hemispheric asymmetry of gaze deviation and relationship to neglect in acute
      stroke.
AB  - Using data from the Trial of Org 10172 in Acute Stroke Treatment (TOAST), the
      authors studied the anatomy of gaze deviation (GD) after stroke and its co
      occurrence with neglect. GD was more frequent and persistent after right
      hemisphere damage. GD was most common with lesions involving the frontal lobes,
      although rates with lesions restricted to other hemispheric regions were not
      significantly different. There was no difference in its rate of co-occurrence
      with neglect between right- and nonright-handed patients.

PMID- 16301503
TI  - Early posttraumatic subarachnoid hemorrhage due to dissecting aneurysms in three
      children.
AB  - Subarachnoid hemorrhage (SAH) due to a ruptured saccular aneurysm is uncommon in
      children. Pediatric traumatic aneurysms have been reported relatively frequently,
      tending to bleed after an interval of weeks after head injury. The authors
      describe three children with acute SAH after head injury caused by intracranial
      dissecting aneurysms. When head trauma in children is complicated by SAH in basal
      cisterns, dissecting aneurysms should be considered and treated, because
      rebleeding may occur.

PMID- 16301504
TI  - Increased incidence of genetic human prion disease in Hungary.
AB  - The authors performed analysis of the prion protein gene (PRNP) in 27 out of 109
      confirmed prion disease patients between 1994 and 2004. E200K mutation was found
      in 17 cases. Another 10 patients, lacking PRNP analysis, showed positive family
      history. The mean annual incidence (0.27/million) and proportion (25.6%) of
      genetic prion disease is unusually high in Hungary and might be related to the
      migration of ancestors from the Slovakian focus.

PMID- 16301505
TI  - Gross muscle pseudohypertrophy in myeloma-associated light chain amyloidosis.

PMID- 16301506
TI  - Dysarthria and dysphagia from light chain amyloidosis.

PMID- 16301507
TI  - X-linked Charcot-Marie-Tooth disease and progressive-relapsing central
      demyelinating disease.

PMID- 16301508
TI  - Autoimmune hearing loss in chronic inflammatory demyelinating polyneuropathy.

PMID- 16301509
TI  - Herpes encephalitis after meningioma resection.

PMID- 16301510
TI  - Rotational vestibular epilepsy from the temporo-parieto-occipital junction.

PMID- 16301511
TI  - Pacemaker-induced tachycardia caused by inappropriate response to parkinsonian
      tremor.

PMID- 16301512
TI  - Essay: Cultivating simple virtues in medicine.

PMID- 16301513
TI  - Intracranial arterial dolichoectasia is associated with enlarged descending
      thoracic aorta.

PMID- 16301514
TI  - Progressive outer retinal necrosis presenting with isolated optic neuropathy.

PMID- 16301515
TI  - Posterior thalamic hemorrhage induces "pusher syndrome".

PMID- 16301516
TI  - Cardiovascular risk factors and migraine: the GEM population-based study.

PMID- 16301517
TI  - Gene transfer of human acid sphingomyelinase corrects neuropathology and motor
      deficits in a mouse model of Niemann-Pick type A disease.
AB  - Niemann-Pick type A disease is a lysosomal storage disorder caused by a
      deficiency in acid sphingomyelinase (ASM) activity. Previously we showed that
      storage pathology in the ASM knockout (ASMKO) mouse brain can be corrected by
      adeno-associated virus serotype 2 (AAV2)-mediated gene transfer. The present
      experiment compared the relative therapeutic efficacy of different recombinant
      AAV serotype vectors (1, 2, 5, 7, and 8) using histological, biochemical, and
      behavioral endpoints. In addition, we evaluated the use of the deep cerebellar
      nuclei (DCN) as a site for injection to facilitate global distribution of the
      viral vector and enzyme. Seven-week-old ASM knockout mice were injected within
      the DCN with different AAV serotype vectors encoding human ASM (hASM) and then
      killed at either 14 or 20 weeks of age. Results showed that AAV1 was superior to
      serotypes 2, 5, 7, and 8 in its relative ability to express hASM, alleviate
      storage accumulation, and correct behavioral deficits. Expression of hASM was
      found not only within the DCN, but also throughout the cerebellum, brainstem,
      midbrain, and spinal cord. This finding demonstrates that targeting the DCN is an
      effective approach for achieving widespread enzyme distribution throughout the
      CNS. Our results support the continued development of AAV based vectors for gene
      therapy of the CNS manifestations in Niemann-Pick type A disease.

PMID- 16301518
TI  - Probing conformational changes in T7 RNA polymerase during initiation and
      termination by using engineered disulfide linkages.
AB  - During the transition from an initiation complex to an elongation complex (EC),
      the single-subunit bacteriophage T7 RNA polymerase (RNAP) undergoes dramatic
      conformational changes. To explore the significance of these changes, we
      constructed mutant RNAPs that are able to form disulfide bonds that limit the
      mobility of elements that are involved in the transition (or its reversal) and
      examined the effects of the crosslinks on initiation and termination. A crosslink
      that is specific to the initiation complex conformation blocks transcription at 5
      6 nt, presumably by preventing isomerization to an EC. A crosslink that is
      specific to the EC conformation has relatively little effect on elongation or on
      termination at a class I terminator (T), which involves the formation of a stable
      stem-loop structure in the RNA. Crosslinked ECs also pause and resume
      transcription normally at a class II pause site (concatamer junction) but are
      deficient in termination at a class II terminator (PTH, which is found in human
      preparathyroid hormone gene), both of which involve a specific recognition
      sequence. The crosslinked amino acids in the EC lie close to the upstream end of
      the RNA-DNA hybrid and may prevent a movement of the polymerase that would assist
      in displacing or releasing RNA from a relatively unstable DNA-RNA hybrid in the
      paused PTH complex.

PMID- 16301519
TI  - Root functioning modifies seasonal climate.
AB  - Hydraulic redistribution (HR), the nocturnal vertical transfer of soil water from
      moister to drier regions in the soil profile by roots, has now been observed in
      Amazonian trees. We have incorporated HR into an atmospheric general circulation
      model (the National Center for Atmospheric Research Community Atmospheric Model
      Version 2) to estimate its impact on climate over the Amazon and other parts of
      the globe where plants displaying HR occur. Model results show that
      photosynthesis and evapotranspiration increase significantly in the Amazon during
      the dry season when plants are allowed to redistribute soil water. Plants draw
      water up and deposit it into the surface layers, and this water subsidy sustains
      transpiration at rates that deep roots alone cannot accomplish. The water used
      for dry season transpiration is from the deep storage layers in the soil,
      recharged during the previous wet season. We estimate that HR increases dry
      season (July to November) transpiration by approximately 40% over the Amazon. Our
      model also indicates that such an increase in transpiration over the Amazon and
      other drought-stressed regions affects the seasonal cycles of temperature through
      changes in latent heat, thereby establishing a direct link between plant root
      functioning and climate.

PMID- 16301520
TI  - Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling
      protein off the mitochondria to evade innate immunity.
AB  - Hepatitis C virus (HCV) is a global epidemic manifested mainly by chronic
      infection. One strategy that HCV employs to establish chronic infection is to use
      the viral Ser protease NS3/4A to cleave some unknown cellular targets involved in
      innate immunity. Here we show that the target of NS3/4A is the mitochondrial
      antiviral signaling protein, MAVS, that activates NF-kappaB and IFN regulatory
      factor 3 to induce type-I interferons. NS3/4A cleaves MAVS at Cys-508, resulting
      in the dislocation of the N-terminal fragment of MAVS from the mitochondria.
      Remarkably, a point mutation of MAVS at Cys-508 renders MAVS resistant to
      cleavage by NS3/4A, thus maintaining the ability of MAVS to induce interferons in
      HCV replicon cells. NS3/4A binds to and colocalizes with MAVS in the
      mitochondrial membrane, and it can cleave MAVS directly in vitro. These results
      provide an example of host-pathogen interaction in which the virus evades innate
      immunity by dislodging a pivotal antiviral protein from the mitochondria and
      suggest that blocking the cleavage of MAVS by NS3/4A may be applied to the
      prevention and treatment of HCV.

PMID- 16301521
TI  - Frequency effects in compound production.
AB  - Four experiments investigated the role of frequency information in compound
      production by independently varying the frequencies of the first and second
      constituent as well as the frequency of the compound itself. Pairs of Dutch noun
      noun compounds were selected such that there was a maximal contrast for one
      frequency while matching the other two frequencies. In a position-response
      association task, participants first learned to associate a compound with a
      visually marked position on a computer screen. In the test phase, participants
      had to produce the associated compound in response to the appearance of the
      position mark, and we measured speech onset latencies. The compound production
      latencies varied significantly according to factorial contrasts in the
      frequencies of both constituting morphemes but not according to a factorial
      contrast in compound frequency, providing further evidence for decompositional
      models of speech production. In a stepwise regression analysis of the joint data
      of Experiments 1-4, however, compound frequency was a significant nonlinear
      predictor, with facilitation in the low-frequency range and a trend toward
      inhibition in the high-frequency range. Furthermore, a combination of structural
      measures of constituent frequencies and entropies explained significantly more
      variance than a strict decompositional model, including cumulative root frequency
      as the only measure of constituent frequency, suggesting a role for paradigmatic
      relations in the mental lexicon.

PMID- 16301522
TI  - Studies of the distribution of Escherichia coli cAMP-receptor protein and RNA
      polymerase along the E. coli chromosome.
AB  - Chromatin immunoprecipitation and high-density microarrays have been used to
      monitor the distribution of the global transcription regulator Escherichia coli
      cAMP-receptor protein (CRP) and RNA polymerase along the E. coli chromosome. Our
      results identify targets occupied by CRP and genes transcribed by RNA polymerase
      in vivo. Many of the loci of CRP binding are at known CRP regulated promoters.
      However, our results show that CRP also interacts with thousands of weaker sites
      across the whole chromosome and that this "background" binding can be used as a
      probe for organization within the E. coli folded chromosome. In rapidly growing
      cells, we show that the major sites of RNA polymerase binding are approximately
      90 transcription units that include genes needed for protein synthesis. Upon the
      addition of rifampicin, RNA polymerase is distributed among >500 functional
      promoters. We show that the chromatin immunoprecipitation and high-density
      microarrays methodology can be used to study the redistribution of RNA polymerase
      induced by environmental stress, revealing previously uncharacterized aspects of
      RNA polymerase behavior and providing an alternative to the "transcriptomics"
      approach for studying global transcription patterns.

PMID- 16301523
TI  - Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late
      onset mitochondrial disease in mice.
AB  - Defects of mitochondrial DNA (mtDNA) maintenance have recently been associated
      with inherited neurodegenerative and muscle diseases and the aging process.
      Twinkle is a nuclear-encoded mtDNA helicase, dominant mutations of which cause
      adult-onset progressive external ophthalmoplegia (PEO) with multiple mtDNA
      deletions. We have generated transgenic mice expressing mouse Twinkle with PEO
      patient mutations. Multiple mtDNA deletions accumulate in the tissues of these
      mice, resulting in progressive respiratory dysfunction and chronic late-onset
      mitochondrial disease starting at 1 year of age. The muscles of the mice
      faithfully replicate all of the key histological, genetic, and biochemical
      features of PEO patients. Furthermore, the mice have progressive deficiency of
      cytochrome c oxidase in distinct neuronal populations. These "deletor" mice do
      not, however, show premature aging, indicating that subtle accumulation of mtDNA
      deletions and progressive respiratory chain dysfunction are not sufficient to
      accelerate aging. This model is a valuable tool for therapy development and
      testing for adult-onset mitochondrial disorders.

PMID- 16301524
TI  - Activation-coupled inactivation in the bacterial potassium channel KcsA.
AB  - X-ray structures of the bacterial K+ channel KcsA have led to unparalleled
      progress in our understanding of ion channel structures. The KcsA channel has
      therefore been a prototypic model used to study the structural basis of ion
      channel function, including the gating mechanism. This channel was previously
      found to close at near-neutral intracellular pH (pH(i)) and to open at acidic
      pH(i). Here, we report the presence of a previously unknown channel inactivation
      process that occurs after the KcsA channel is activated. In our experiments,
      mammalian cells transfected with a codon-optimized synthetic gene encoding the
      KcsA protein expressed K+-selective channels that activated in response to a
      decrease in pH(i). Using patch-clamp and rapid solution exchange techniques, we
      observed that the KcsA channels inactivated within hundreds of milliseconds after
      channel activation. At all tested pHs, inactivation always accompanied
      activation, and it was profoundly accelerated in the same pH range at which
      activation increased steeply. Recovery from inactivation was observed, and its
      extent depended on the pH(i) and the amount of time that the channel was
      inactive. KcsA channel inactivation can be described by a kinetic model in which
      pH(i) controls inactivation through pH-dependent activation. This heretofore
      undocumented inactivation process increases the complexity of KcsA channel
      function, but it also offers a potential model for studying the structural
      correspondence of ion channel inactivation.

PMID- 16301525
TI  - Inactivation of the Snf5 tumor suppressor stimulates cell cycle progression and
      cooperates with p53 loss in oncogenic transformation.
AB  - Snf5 (Ini1/Baf47/Smarcb1), a core member of the Swi/Snf chromatin remodeling
      complex, is a potent tumor suppressor whose mechanism of action is largely
      unknown. Biallelic loss of Snf5 leads to the onset of aggressive cancers in both
      humans and mice. We have developed an innovative and widely applicable analytical
      technique for cross-species validation of cancer models and show that the gene
      expression profiles of our Snf5 murine models closely resemble those of human
      Snf5-deficient rhabdoid tumors. We exploit this system to produce what we believe
      to be the first report documenting the effects on gene expression of inactivating
      a Swi/Snf subunit in normal mammalian cells and to identify the transcriptional
      pathways regulated by Snf5. We demonstrate that the tumor suppressor activity of
      Snf5 depends on its regulation of cell cycle progression; Snf5 inactivation leads
      to aberrant up-regulation of E2F targets and increased levels of p53 that are
      accompanied by apoptosis, polyploidy, and growth arrest. Further, conditional
      mouse models demonstrate that inactivation of p16Ink4a or Rb (retinoblastoma)
      does not accelerate tumor formation in Snf5 conditional mice, whereas mutation of
      p53 leads to a dramatic acceleration of tumor formation.

PMID- 16301526
TI  - Identification of oligonucleotide sequences that direct the movement of the
      Escherichia coli FtsK translocase.
AB  - FtsK from Escherichia coli is a fast and sequence-directed DNA translocase with
      roles in chromosome dimer resolution, segregation, and decatenation. From the
      movement of single FtsK particles on defined DNA substrates and an analysis of
      skewed DNA sequences in bacteria, we identify GNGNAGGG, its complement, or both
      as a sequence motif that controls translocation directionality. GNGNAGGG is
      skewed so that it is predominantly on the leading strand of chromosomal
      replication. Translocation across this octamer from the 3' side of the G-rich
      strand causes FtsK to pause, turn around, and translocate in the opposite
      direction. Only 39 +/- 4% of the encounters between FtsK and the octamer result
      in a turnaround, congruent with our optimum turnaround probability prediction of
      30%. The probability that the observed skew of GNGNAGGG within 1 megabase of dif
      occurred by chance in E. coli is 1.7 x 10(-57), and similarly dramatic skews are
      found in the five other bacterial genomes we examined. The fact that FtsK acts
      only in the terminus region and the octamer skew extends from origin to terminus
      implies that this skew is also important in other basic cellular processes that
      are common among bacteria. Finally, we show that the FtsK translocase is a
      powerful motor that is able to displace a triplex-forming oligo from a DNA
      substrate.

PMID- 16301527
TI  - Beta-catenin regulates myogenesis by relieving I-mfa-mediated suppression of
      myogenic regulatory factors in P19 cells.
AB  - Wnt/beta-catenin signaling plays a critical role in embryonic myogenesis. Here we
      show that, in P19 embryonic carcinoma stem cells, Wnt/beta-catenin signaling
      initiates the myogenic process depends on beta-catenin-mediated relief of I-mfa
      (inhibitor of MyoD Family a) suppression of myogenic regulatory factors (MRFs).
      We found that beta-catenin interacted with I-mfa and that the interaction was
      enhanced by Wnt3a. In addition, we found that the interaction between beta
      catenin and I-mfa was able to attenuate the interaction of I-mfa with MRFs,
      relieve I-mfa-mediated suppression of the transcriptional activity and cytosolic
      sequestration of MRFs, and initiate myogenesis in a P19 myogenic model system
      that expresses exogenous myogenin. This work reveals a mechanism for the
      regulation of MRFs during myogenesis by elucidating a beta-catenin-mediated, but
      lymphoid enhancing factor-1/T cell factor independent, mechanism in regulation of
      myogenic fate specification and differentiation of P19 mouse stem cells.

PMID- 16301528
TI  - Negative regulation of Salmonella pathogenicity island 2 is required for
      contextual control of virulence during typhoid.
AB  - Salmonella enterica relies on a type III secretion system encoded in Salmonella
      pathogenicity island-2 (SPI-2) to survive and replicate within macrophages at
      systemic sites during typhoid. SPI-2 virulence is induced upon entry into
      macrophages, but the mechanisms of SPI-2 gene control in vivo remain unclear,
      particularly with regard to negative regulators that control the contextual
      activation of SPI-2. Here, we identified and characterized YdgT as a negative
      modulator of the SPI-2 pathogenicity island and established that this negative
      regulation is central to systemic pathogenesis because ydgT mutants
      overexpressing typhoid virulence genes were ultimately attenuated during
      infection. ydgT mutants displayed a biphasic virulence phenotype during in vivo
      competitive infections that consisted of an early "gain-of-virulence" dependent
      on SPI-2 activation, followed by attenuation later in infection indicating that
      proper contextual regulation of SPI-2 by YdgT is necessary for full virulence
      during systemic colonization. These data suggest that overexpression of virulence
      associated type III secretion genes can have an adverse effect on bacterial
      pathogenesis in vivo.

PMID- 16301529
TI  - Aryl hydrocarbon receptor-dependent liver development and hepatotoxicity are
      mediated by different cell types.
AB  - The aryl hydrocarbon receptor (AHR) plays a role in three areas of biology that
      include the adaptive metabolism of xenobiotics, the toxic responses associated
      with exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), and vascular
      remodeling of the developing embryo. To test the hypothesis that receptor
      signaling in different cell types is responsible for these aspects of AHR
      biology, we generated a conditional Ahr allele where exon 2 is flanked by loxP
      sites. Through the use of Cre-lox technology, we then investigated the role of
      AHR signaling in hepatocytes or endothelial cells in mediating prototypical
      endpoints of adaptive, toxic, or developmental signaling. Using this model, we
      provide evidence that AHR signaling in endothelial/hematopoietic cells is
      necessary for developmental closure of the ductus venosus, whereas AHR signaling
      in hepatocytes is necessary to generate adaptive and toxic responses of the liver
      in response to dioxin exposure. Taken together, these data illustrate the
      importance of cell-specific receptor signaling for the generation of distinct AHR
      dependent physiological outcomes.

PMID- 16301530
TI  - Transgenic rice for allergy immunotherapy.

PMID- 16301531
TI  - Crosstalk in G protein-coupled receptors: changes at the transmembrane homodimer
      interface determine activation.
AB  - Functional crosstalk between G protein-coupled receptors in a homo- or
      heterodimeric assembly likely involves conformational changes at the dimer
      interface, but the nature of this interface is not yet established, and the
      dynamic changes have not yet been identified. We have mapped the homodimer
      interface in the dopamine D2 receptor over the entire length of the fourth
      transmembrane segment (TM4) by crosslinking of substituted cysteines. Their
      susceptibilities to crosslinking are differentially altered by the presence of
      agonists and inverse agonists. The TM4 dimer interface in the inverse agonist
      bound conformation is consistent with the dimer of the inactive form of rhodopsin
      modeled with constraints from atomic force microscopy. Crosslinking of a
      different set of cysteines in TM4 was slowed by inverse agonists and accelerated
      in the presence of agonists; crosslinking of the latter set locks the receptor in
      an active state. Thus, a conformational change at the TM4 dimer interface is part
      of the receptor activation mechanism.

PMID- 16301532
TI  - Gemin proteins are required for efficient assembly of Sm-class
      ribonucleoproteins.
AB  - Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by
      loss of spinal motor neurons. The gene encoding the survival of motor neurons
      (SMN) protein is mutated in >95% of SMA cases. SMN is the central component of a
      large oligomeric complex, including Gemins2-7, that is necessary and sufficient
      for the in vivo assembly of Sm proteins onto the small nuclear (sn)RNAs that
      mediate pre-mRNA splicing. After cytoplasmic assembly of the Sm core, both SMN
      and splicing snRNPs are imported into the nucleus, accumulating in Cajal bodies
      for additional snRNA maturation steps before targeting to splicing factor
      compartments known as "speckles." In this study, we analyzed the function of
      individual SMN complex members by RNA interference (RNAi). RNAi-mediated
      knockdown of SMN, Gemin2, Gemin3, and Gemin4 each disrupted Sm core assembly,
      whereas knockdown of Gemin5 and Snurportin1 had no effect. Assembly activity was
      rescued by expression of a GFP-SMN construct that is refractive to RNAi but not
      by similar constructs that contain SMA patient-derived mutations. Our results
      also demonstrate that Cajal body homeostasis requires SMN and ongoing snRNP
      biogenesis. Perturbation of SMN function results in disassembly of Cajal bodies
      and relocalization of the marker protein, coilin, to nucleoli. Moreover, in SMN
      deficient cells, newly synthesized SmB proteins fail to associate with U2 snRNA
      or accumulate in Cajal bodies. Collectively, our results identify a previously
      uncharacterized function for Gemin3 and Gemin4 in Sm core assembly and correlate
      the activity of this pathway with SMA.

PMID- 16301533
TI  - The DHHC protein Pfa3 affects vacuole-associated palmitoylation of the fusion
      factor Vac8.
AB  - Vacuole biogenesis depends on specific targeting and retention of peripheral
      membrane proteins. At least three palmitoylated proteins are found exclusively on
      yeast vacuoles: the fusion factor Vac8, the kinase Yck3, and a novel adaptor
      protein implicated in microautophagy, Meh1. Here, we analyze the role that
      putative acyltransferases of the DHHC family play in their localization and
      function. We find that Pfa3/Ynl326c is required for efficient localization of
      Vac8 to vacuoles in vivo, while Yck3 or Meh1 localization is not impaired in any
      of the seven DHHC deletions. Vacuole-associated Vac8 appears to be palmitoylated
      in a pfa3 mutant, but this population is refractive to further palmitoylation on
      isolated vacuoles. Vacuole morphology and inheritance, which both depend on Vac8
      palmitoylation, appear normal, although there is a reduction in vacuole fusion.
      Interestingly, Pfa3 is required for the vacuolar localization of not only an SH4
      domain that is targeted by myristate/palmitate (as in Vac8) but also one that is
      targeted by a myristate/basic stretch (as in Src). Our data indicate that Pfa3
      has an important but not exclusive function for Vac8 localization to the vacuole.

PMID- 16301534
TI  - "Clonal" population structure of the malaria agent Plasmodium falciparum in high
      infection regions.
AB  - The population genetic structure of Plasmodium falciparum, the agent of malignant
      malaria, has been shown to be predominantly "clonal" (i.e., highly inbred) in
      regions of low infectivity; in high-infectivity regions, it is often thought to
      be panmictic, or nearly so, although there is little supporting evidence for
      this. The matter can be settled by investigating the parasite's genetic makeup in
      the midgut oocysts of the mosquito vector, where the products of meiosis can
      directly be observed. The developmental stages of P. falciparum are haploid,
      except in the oocysts of infected mosquito vectors, where two gametes fuse,
      diploidy occurs, and meiosis ensues. We have investigated genetic polymorphisms
      at seven microsatellite loci located on five chromosomes by assaying 613 oocysts
      in 145 mosquitoes sampled from 11 localities of Kenya, where malignant malaria is
      perennial and intense. There is considerable allelic variation, 16.3 +/- 2.1
      alleles per locus, and considerable inbreeding, approximately 50% on the average.
      The inbreeding is caused by selfing (approximately 25%) and nonrandom genotype
      distribution of oocysts among mosquito guts (35%). The observed frequency of
      heterozygotes is 0.43 +/- 0.03; the expected frequency, assuming random mating,
      is 0.80 +/- 0.05. Linkage disequilibrium is statistically significant for all 21
      pairwise comparisons between loci, even though 19 comparisons are between loci in
      different chromosomes, which is consistent with strong deviation from panmixia
      and the consequent reproduction of genomes as clones, without recombination
      between gene loci. This is of considerable evolutionary significance and of
      epidemiological consequence, concerning the spread of multilocus drug and vaccine
      resistance.

PMID- 16301535
TI  - Light-switching excimer probes for rapid protein monitoring in complex biological
      fluids.
AB  - Quantitative protein bioanalysis in complex biological fluids presents
      considerable challenges in biological studies and disease diagnosis. The major
      obstacles are the background signals from both the probe and the biological
      fluids where the proteins reside. We have molecularly engineered light-switching
      excimer aptamer probes for rapid and sensitive detection of a biomarker protein,
      platelet-derived growth factor (PDGF). Labeled with one pyrene at each end, the
      aptamer switches its fluorescence emission from approximately 400 nm (pyrene
      monomer) to 485 nm (pyrene excimer) upon PDGF binding. This fluorescence
      wavelength change from monomer to excimer emission is a result of aptamer
      conformation rearrangement induced by target binding. The excimer probe is able
      to effectively detect picomolar PDGF in homogeneous solutions. Because the
      excimer has a much longer fluorescence lifetime (approximately 40 ns) than that
      of the background (approximately 5 ns), time-resolved measurements were used to
      eliminate the biological background. We thus were able to detect PDGF in a cell
      sample quantitatively without any sample pretreatment. This molecular engineering
      strategy can be used to develop other aptamer probes for protein monitoring.
      Combined with lifetime-based measurements and molecular engineering, light
      switching excimer aptamer probes hold great potential in protein analysis for
      biomedical studies.

PMID- 16301536
TI  - A data integration methodology for systems biology: experimental verification.
AB  - The integration of data from multiple global assays is essential to understanding
      dynamic spatiotemporal interactions within cells. In a companion paper, we
      reported a data integration methodology, designated Pointillist, that can handle
      multiple data types from technologies with different noise characteristics. Here
      we demonstrate its application to the integration of 18 data sets relating to
      galactose utilization in yeast. These data include global changes in mRNA and
      protein abundance, genome-wide protein-DNA interaction data, database
      information, and computational predictions of protein-DNA and protein-protein
      interactions. We divided the integration task to determine three network
      components: key system elements (genes and proteins), protein-protein
      interactions, and protein-DNA interactions. Results indicate that the
      reconstructed network efficiently focuses on and recapitulates the known biology
      of galactose utilization. It also provided new insights, some of which were
      verified experimentally. The methodology described here, addresses a critical
      need across all domains of molecular and cell biology, to effectively integrate
      large and disparate data sets.

PMID- 16301537
TI  - A data integration methodology for systems biology.
AB  - Different experimental technologies measure different aspects of a system and to
      differing depth and breadth. High-throughput assays have inherently high false
      positive and false-negative rates. Moreover, each technology includes systematic
      biases of a different nature. These differences make network reconstruction from
      multiple data sets difficult and error-prone. Additionally, because of the rapid
      rate of progress in biotechnology, there is usually no curated exemplar data set
      from which one might estimate data integration parameters. To address these
      concerns, we have developed data integration methods that can handle multiple
      data sets differing in statistical power, type, size, and network coverage
      without requiring a curated training data set. Our methodology is general in
      purpose and may be applied to integrate data from any existing and future
      technologies. Here we outline our methods and then demonstrate their performance
      by applying them to simulated data sets. The results show that these methods
      select true-positive data elements much more accurately than classical
      approaches. In an accompanying companion paper, we demonstrate the applicability
      of our approach to biological data. We have integrated our methodology into a
      free open source software package named POINTILLIST.

PMID- 16301538
TI  - Knockout of caspase-like gene, YCA1, abrogates apoptosis and elevates oxidized
      proteins in Saccharomyces cerevisiae.
AB  - In our previous study, we established that inhibition of apoptosis by the general
      caspase inhibitor is associated with an increase in the level of oxidized
      proteins in a multicellular eukaryotic system. To gain further insight into a
      potential link between oxidative stress and apoptosis, we carried out studies
      with Saccharomyces cerevisiae, which contains a gene (YCA1) that encodes
      synthesis of metacaspase, a homologue of the mammalian caspase, and is known to
      play a crucial role in the regulation of yeast apoptosis. We show that upon
      exposure to H(2)O(2), the accumulation of protein carbonyls is much greater in a
      Delta yca1 strain lacking the YCA1 gene than in the wild type and that apoptosis
      was abrogated in the Delta yca1 strain, whereas wild type underwent apoptosis as
      measured by externalization of phosphatidylserine and the display of TUNEL
      positive nuclei. We also show that H(2)O(2)-mediated stress leads to up
      regulation of the 20S proteasome and suppression of ubiquitinylation activities.
      These findings suggest that deletion of the apoptotic-related caspase-like gene
      leads to a large H(2)O(2)-dependent accumulation of oxidized proteins and up
      regulation of 20S proteasome activity.

PMID- 16301539
TI  - Fcp1 directly recognizes the C-terminal domain (CTD) and interacts with a site on
      RNA polymerase II distinct from the CTD.
AB  - Fcp1 is an essential protein phosphatase that hydrolyzes phosphoserines within
      the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II).
      Fcp1 plays a major role in the regulation of CTD phosphorylation and, hence,
      critically influences the function of Pol II throughout the transcription cycle.
      The basic understanding of Fcp1-CTD interaction has remained ambiguous because
      two different modes have been proposed: the "dockingsite" model versus the
      "distributive" mechanism. Here we demonstrate biochemically that Fcp1 recognizes
      and dephosphorylates the CTD directly, independent of the globular non-CTD part
      of the Pol II structure. We point out that the recognition of CTD by the
      phosphatase is based on random access and is not driven by Pol II conformation.
      Results from three different types of experiments reveal that the overall
      interaction between Fcp1 and Pol II is not stable but dynamic. In addition, we
      show that Fcp1 also interacts with a region on the polymerase distinct from the
      CTD. We emphasize that this non-CTD site is functionally distinct from the
      docking site invoked previously as essential for the CTD phosphatase activity of
      Fcp1. We speculate that Fcp1 interaction with the non-CTD site may mediate its
      stimulatory effect on transcription elongation reported previously.

PMID- 16301540
TI  - Structure of a nonheme globin in environmental stress signaling.
AB  - RsbR is a regulator of sigma(B), the RNA polymerase sigma factor subunit
      responsible for transcribing the general stress response genes when environmental
      stress is imposed on Bacillus subtilis. The C-terminal domain of RsbR and its
      paralogues is a substrate for the kinase function of another sigma(B) regulator,
      RsbT, but the amino acid sequence of the N-terminal domain of RsbR does not
      reveal any obvious biochemical function. RsbR, its paralogues, and other
      regulators of sigma(B), including RsbS and RsbT, form large signaling complexes,
      called stressosomes. We have determined and present here the crystal structure of
      the N-terminal domain of RsbR. Unexpectedly, this structure belongs to the globin
      fold superfamily, but there is no bound cofactor. The globin domain from globin
      coupled sensory systems replaces the N-terminal domain of RsbR in some bacteria,
      indicating a common genetic ancestry for RsbR and the globin family. We suggest
      that the globin fold has been "recycled" in RsbR and that one more activity can
      be included in the repertoire of globin functions, namely the ability to bind
      signaling macromolecules such as RsbT.

PMID- 16301541
TI  - Oxygen isotopes indicate most intracellular water in log-phase Escherichia coli
      is derived from metabolism.
AB  - The transport of water into and out of unicellular organisms is a seemingly
      simple process in which water diffuses either through pores or directly across
      the membrane. Because of the rates at which water can theoretically diffuse, it
      is generally accepted that intracellular water is indistinguishable from
      extracellular water. Using stable isotope ratio mass spectrometry, we directly
      tested this assumption. Here we demonstrate that under active growth, up to 70%
      of the intracellular water in log-phase Escherichia coli cells was actually
      generated during metabolism and was isotopically distinct from extracellular
      water. The contribution of metabolism to intracellular water was substantially
      less in stationary-phase or quiescent cells.

PMID- 16301542
TI  - Transcriptome profiling of bacterial responses to root exudates identifies genes
      involved in microbe-plant interactions.
AB  - Molecules exuded by plant roots are thought to act as signals to influence the
      ability of microbial strains to colonize the roots and to survive in the
      rhizosphere. Differential bacterial responses to signals from different plant
      species may mediate the selection of specific rhizosphere populations. Very
      little, however, is known about the effects of plant exudates on patterns of
      bacterial gene expression. Here, we have tested the concept that plant root
      exudates modulate expression of bacterial genes involved in establishing microbe
      plant interactions. We have examined the influence on the Pseudomonas aeruginosa
      PA01 transcriptome of exudates from two varieties of sugarbeet that select for
      genetically distinct pseudomonad populations in the rhizosphere. The response to
      the two exudates showed only a partial overlap; the majority of those genes with
      altered expression was regulated in response to only one of the two exudates.
      Genes with altered expression included those with functions previously implicated
      in microbe-plant interactions, such as aspects of metabolism, chemotaxis and type
      III secretion, and a subset with putative or unknown function. Use of a panel of
      mutants with targeted disruptions allowed us to identify previously
      uncharacterized genes with roles in the competitive ability of P. aeruginosa in
      the rhizosphere within this subset. No genes with host-specific effects were
      identified. Homologues of the genes identified occur in the genomes of both
      beneficial and pathogenic root-associated bacteria, suggesting that this strategy
      may help to elucidate molecular interactions that are important for biocontrol,
      plant growth promotion, and plant pathogenesis.

PMID- 16301543
TI  - Identifying the conserved network of cis-regulatory sites of a eukaryotic genome.
AB  - A major focus of genome research has been to decipher the cis-regulatory code
      that governs complex transcriptional regulation. We report a computational
      approach for identifying conserved regulatory motifs of an organism directly from
      whole genome sequences of several related species without reliance on additional
      information. We first construct phylogenetic profiles for each promoter, then use
      a BLAST-like algorithm to efficiently search through the entire profile space of
      all of the promoters in the genome to identify conserved motifs and the promoters
      that contain them. Statistical significance is estimated by modified Karlin
      Altschul statistics. We applied this approach to the analysis of 3,524
      Saccharomyces cerevisiae promoters and identified a highly organized regulatory
      network involving 3,315 promoters and 296 motifs. This network includes nearly
      all of the currently known motifs and covers >90% of known transcription factor
      binding sites. Most of the predicted coregulated gene clusters in the network
      have additional supporting evidence. Theoretical analysis suggests that our
      algorithm should be applicable to much larger genomes, such as the human genome,
      without reaching its statistical limitation.

PMID- 16301545
TI  - Tongue tie.

PMID- 16301544
TI  - Charting biologically relevant chemical space: a structural classification of
      natural products (SCONP).
AB  - The identification of small molecules that fall within the biologically relevant
      subfraction of vast chemical space is of utmost importance to chemical biology
      and medicinal chemistry research. The prerequirement of biological relevance to
      be met by such molecules is fulfilled by natural product-derived compound
      collections. We report a structural classification of natural products (SCONP) as
      organizing principle for charting the known chemical space explored by nature.
      SCONP arranges the scaffolds of the natural products in a tree-like fashion and
      provides a viable analysis- and hypothesis-generating tool for the design of
      natural product-derived compound collections. The validity of the approach is
      demonstrated in the development of a previously undescribed class of selective
      and potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 with activity
      in cells guided by SCONP and protein structure similarity clustering. 11beta
      hydroxysteroid dehydrogenase type 1 is a target in the development of new
      therapies for the treatment of diabetes, the metabolic syndrome, and obesity.

PMID- 16301546
TI  - Children with diabetes benefit from exercise.

PMID- 16301547
TI  - Inter-hospital transport for children and their parent(s).

PMID- 16301548
TI  - "The joy to bless and to relieve mankind": child healthcare at Northampton
      General Infirmary 1744.
AB  - For more than a century before the opening of Great Ormond Street Hospital for
      Children (1852), children in England were treated and even admitted in voluntary
      hospitals in spite of rules prohibiting such care. The earliest English
      eighteenth century records, that contain the patient's age, are held in
      Northampton. Reviewing records from the Northampton General Infirmary (from 1903
      the Northampton General Hospital) for the period 1744-45 gives a flavour of
      hospital child health care in an era before the formal recognition of paediatrics
      as a medical specialty and the construction of specialist provision. Indeed the
      first patient admitted to the Northampton General Infirmary on 29 March 1744 was
      Thomasin Grace, a 13 year old child. In Northampton, in its first year of
      operation, children as young as 2 years of age were seen in outpatients and from
      8 years were admitted. Paediatric cases up to and including those 16 years of age
      made up 26% of the number of patients seen for that year. Within the first year
      of opening for children of 10 years of age and under, there were eight inpatient
      admissions and 18 children were treated in outpatients.

PMID- 16301549
TI  - Sleep disturbance in Sanfilippo syndrome: a parental questionnaire study.
AB  - AIMS: To determine the incidence, manifestations, and best management of sleep
      disturbance in Sanfilippo syndrome (mucopolysaccharidosis (MPS) type III).
      METHODS: Families were ascertained through the MPS societies of Australasia, the
      UK, and the USA. Questionnaires were sent by mail and were answered anonymously.
      Identical questions regarding sleep disturbance were asked about unaffected
      siblings to provide control data. Sleep disturbance was quantified by a total
      sleep disturbance score. RESULTS: A total of 141 responses were received; 91.5%
      of children with Sanfilippo syndrome had sleep disturbance and this was
      significantly higher than for their unaffected sibs; 77.5% of parents had used
      medication for this problem, with melatonin and antihistamines being most
      commonly used. Melatonin and benzodiazepines were reported as the most
      efficacious. Many different environmental modifications had been employed for
      this problem and some parents reported success with behavioural therapies.
      CONCLUSIONS: Sleep disturbance is common, severe, and difficult to manage in
      Sanfilippo syndrome. Based on the parental responses and its safety profile,
      melatonin is the first line drug that should be tried. Behavioural therapy should
      be tried in all with Sanfilippo syndrome and sleep disturbance.

PMID- 16301550
TI  - Hospitalisations from birth to 5 years in a population cohort of Western
      Australian children with intellectual disability.
AB  - AIMS: To describe the hospitalisation history in the first five years of life for
      all children born in Western Australia (WA) between 1983 and 1992 and diagnosed
      with intellectual disability (ID). METHODS: Unit record linkage of the WA
      Midwives Collection, WA Intellectual Disability Database, and the WA Hospital
      Morbidity Dataset provided the population database of WA born children with and
      without ID. Affected children were divided into those co-affected with autism
      spectrum disorders (ASD), and those whose ID had or had no known biomedical
      cause. Those without a biomedical cause were further subdivided into mild
      moderate and severe categories. RESULTS: On average, ID affected children were
      more likely than non-affected children to be admitted to hospital (RR: 1.64; 95%
      CI 1.6 to 1.7), on more occasions (5.3 versus 2.2 admissions), for longer (29.6
      versus 8.3 days), and for a larger range of clinical diagnoses. The only
      exception was the group of children co-diagnosed with ASD whose hospitalisation
      profile resembled more that of non-affected children. CONCLUSIONS: This total
      population study is unique because of the availability of the system of linkable
      population registers and administrative health databases in WA. The results
      indicated that this vulnerable population of children with ID has substantial
      medical needs. This paper points to the need for authorities to develop
      supportive programmes for this population especially in the current climate of de
      medicalisation of ID. More research is not only needed on the welfare of the
      affected children but also on the impact of the substantial medical and other
      needs of affected children on the rest of their immediate and extended families.

PMID- 16301551
TI  - Scientific ethics committees: a user's guide.

PMID- 16301552
TI  - Stimulants for paediatricians.

PMID- 16301553
TI  - Managing medication in schools.
AB  - Increasing numbers of children and young people are prescribed medication to be
      taken in school. This article discusses general principles of prescribing
      medication for use in school, specific conditions for which medicines may be
      prescribed, and the key role of nurses in liaison with schools. Decisions about
      prescribing medication for use in schools do not only depend on evidence of
      therapeutic effectiveness but need to take into account other social and
      educational benefits and harms that may occur when children need to use
      medication in school.

PMID- 16301554
TI  - Haemopoietic stem cell transplantation for genetic disorders.
AB  - Stem cell transplantation (SCT) is used to cure or greatly ameliorate a wide
      variety of genetic diseases, ranging from inherent defects of haemopoietic cell
      production or function to metabolic diseases mostly affecting solid organs. It
      ranks as one of the most remarkable therapeutic advances of the past 40 years.
      Despite rapid technological improvements, however, there are still many short
      term risks and potential long term toxicities. As a consequence, the rapid
      emergence of alternative therapies (including new drugs, enzyme and gene
      therapies), necessitate constant re-evaluation of the risk/benefit ratio for each
      disease and hence the appropriateness of SCT. This review describes the major
      aspects of the transplant process, indications for transplantation, outcome
      statistics, and areas where alternative therapies are becoming available.

PMID- 16301555
TI  - Chromosome analysis: what and when to request.
AB  - Chromosome abnormalities have long been recognised as an important cause of
      learning disability and multiple malformation syndromes; 0.8% of live born
      infants have numerical or structural chromosomal anomalies resulting in an
      abnormal phenotype. The identification of such anomalies is important, both
      clinically and for accurate genetic counselling. Recently, the human genome
      sequence has enabled higher resolution screens for chromosome anomalies using
      both molecular cytogenetic and array based techniques. This review suggests a
      simple algorithm for the targeted use of diagnostic cytogenetic tools in specific
      patient groups commonly seen in paediatric practice.

PMID- 16301557
TI  - Palpation reveals the diagnosis.

PMID- 16301556
TI  - Review of Staphylococcus aureus infections requiring admission to a paediatric
      intensive care unit.
AB  - AIMS: To review clinical features and outcome of children with severe
      Staphylococcus aureus sepsis (SAS) presenting to a paediatric intensive care unit
      (PICU) with particular focus on ethnicity, clinical presentation, cardiac
      involvement, and outcome. METHODS: Retrospective chart review of patients coded
      for SAS over 10 years (October 1993 to April 2004). RESULTS: There were 58
      patients identified with SAS over the 10 year study period; 55 were community
      acquired. This accounted for 4% of hospital admissions for SAS over this time;
      children with staphylococcal illness comprised 1% of all admissions to the PICU.
      Maori and Pacific children with SAS were overly represented in the PICU (81%)
      from a paediatric population where they contribute 21.6%. Musculoskeletal
      symptoms (79%) dominated presentation rather than isolated pneumonia (10%). An
      aggressive search for foci and surgical drainage of infective foci was required
      in 50% of children. Most children had multifocal disease (67%) and normal cardiac
      valves (95%); the few children (12%) presenting with methicillin resistant S
      aureus (MRSA) had community acquired infection. The median length of stay in the
      PICU was 3 (mean 5.8, SD 7.6, range 1-44) days. The median length of stay in
      hospital was 15 (mean 21, SD 22.7, range 2-149) days. Mortality due to SAS was
      8.6% (95% CI 1.4-15.8%) compared with the overall mortality for the PICU of 6%
      (95% CI 5.3-6.7%). Ten children had significant morbidity after discharge.
      CONCLUSIONS: Community acquired SAS affects healthy children, is multifocal, and
      has high morbidity and mortality, in keeping with the high severity of illness
      scores on admission. It is imperative to look for sites of dissemination and to
      drain and debride foci. Routine echocardiography had low yield in the absence of
      pre-existing cardiac lesions, persisting fever, or persisting bacteraemia.

PMID- 16301558
TI  - An unwell child with a florid rash.

PMID- 16301560
TI  - Test/don't test?

PMID- 16301559
TI  - Hospital planning for acts of terrorism and other public health emergencies
      involving children.
AB  - In today's world the increased potential of terrorist attacks places unique
      burdens and consequences on health care workers. Hospitals and hospital personnel
      must now be prepared to react immediately to such events. They must also
      implement, in advance, policies to protect their own health care personnel while
      providing care to victims. In this review, we discuss the four major forms of
      mass casualty terrorism (biological, chemical, nuclear, and thermomechanical)
      including clinical signs and symptoms for each, the impact on health care
      personnel, and special considerations for children. We will then outline key
      principles of hospital preparation with regard to paediatrics in anticipation of
      such emergencies.

PMID- 16301561
TI  - Towards evidence based medicine for paediatricians.

PMID- 16301562
TI  - Are the Ottawa ankle rules helpful in ruling out the need for x ray examination
      in children?

PMID- 16301563
TI  - Can transcutaneous bilirubinometry reduce the need for serum bilirubin
      estimations in term and near term infants?

PMID- 16301564
TI  - What is the risk of cancer in a child with hemihypertrophy?

PMID- 16301565
TI  - Dialogue, death, and life choices: a parent's perspective.

PMID- 16301566
TI  - Effectiveness of tonsillectomy depends on stringency of indications.

PMID- 16301567
TI  - The dental health of children with refractory epilepsy in a residential school.

PMID- 16301568
TI  - Bruising in preschool children with special needs.

PMID- 16301569
TI  - A strategy to minimise the impact of maternal HIV.

PMID- 16301570
TI  - Global gene expression profiling: a complement to conventional histopathologic
      analysis of neoplasia.
AB  - Transcriptional profiling of entire tumors has yielded considerable insight into
      the molecular mechanisms of heterogeneous cell populations within different types
      of neoplasms. The data thus acquired can be further refined by microdissection
      methods that enable the analyses of subpopulations of neoplastic cells.
      Separation of the various components of a neoplasm (i.e., stromal cells,
      inflammatory infiltrates, and blood vessels) has been problematic, primarily
      because of a paucity of tools for accurate microdissection. The advent of laser
      capture microdissection combined with powerful tools of linear amplification of
      RNA and high-throughput microarray-based assays have allowed the transcriptional
      mapping of intricate and highly complex networks within pure populations of
      neoplastic cells. With this approach, specific "molecular signatures" can be
      assigned to tumors of distinct or even similar histomorphology, thereby aiding
      the desired objective of pattern recognition, tumor classification, and
      prognostication. This review highlights the potential benefits of global gene
      expression profiling of tumor cells as a complement to conventional
      histopathologic analyses.

PMID- 16301571
TI  - Neuroanatomical phenotyping in the mouse: the dopaminergic system.
AB  - Voluntary movement in animals is modulated by a number of subcortical systems.
      One of these resides in the basal nuclei and their associated projections and
      utilizes dopamine as a neurotransmitter. Apart from regulating movement, the
      dopaminergic axis is also involved in the control of goal-oriented behavior,
      cognition, and mood. Disorders of this system result in common human neurologic
      disorders such as Parkinson's and Huntington's diseases, as well contributing to
      a host of behavioral conditions, such as schizophrenia, attention deficit
      hyperactivity disorder, and addiction. Many individual mouse models of human
      dopaminergic dysfunction have been described in varying degrees of detail.
      However, when evaluating this region of the brain, the veterinary pathologist is
      confronted by a paucity of information summarizing the comparative aspects of the
      anatomy, physiology, and pathology of the central dopaminergic system. In this
      review, a systematic approach to anatomic phenotyping of the central dopaminergic
      system in the mouse is described and illustrated using tyrosine hydroxylase
      immunohistochemistry. Differences between murine neuroanatomy and comparable
      regions of the nonhuman primate brain are highlighted. Although the mouse is the
      focus of this review, conditions in domestic animals characterized by lesions
      within the basal nuclei and its projections are also briefly described. Murine
      behavioral and motor tests that accompany abnormalities of specific anatomic
      regions of the dopaminergic axis are summarized. Finally, we review mouse models
      of Parkinson's and Huntington's diseases, as well as those genetically altered
      mice that elucidate aspects of dopamine metabolism and receptor function.

PMID- 16301573
TI  - Cyclooxygenase-2 expression is associated with histologic tumor type in canine
      mammary carcinoma.
AB  - Cyclooxygenase-2 (COX-2) is an inducible member of the family of cyclooxygenase
      enzymes that has been implicated in the genesis of numerous cancers. The role of
      COX-2 in canine mammary neoplasia remains to be more clearly elucidated. The goal
      of the study reported here was to determine whether a direct association between
      levels of COX-2 expression and tumor histologic subtype exists in canine mammary
      carcinoma. Immunohistochemical analysis was performed using a polyclonal
      antiprostaglandin G/H synthase 2 IgG COX-2 antibody. Sections from the kidneys of
      young dogs, which stain positive for COX-2 in the macula densa, served as
      positive controls. Slides were reviewed by a single pathologist, and were
      evaluated for COX-2 expression according to previously established scales.
      Positive-staining tumors were given a COX-2 staining distribution (on the basis
      of the percentage of positive staining cells in five 400x fields) and intensity
      score according to previously established scales. The product of the COX-2
      staining distribution and intensity scores was calculated to create a COX-2
      staining index. COX-2 expression was detected in 28 of 50 (56%) samples
      evaluated. Anaplastic carcinomas had a significantly higher COX-2 staining
      distribution, intensity, and index, compared with those for adenocarcinomas (P <
      0.0001). The overall percentage of positive tumors (56%) was consistent with that
      of prior studies. To the authors' knowledge, these results indicate, for the
      first time, a direct association between COX-2 expression and tumor histologic
      subtype in canine mammary carcinomas. Future research directed at measuring tumor
      response in canine mammary carcinoma patients treated with a selective COX-2
      inhibitor is indicated.

PMID- 16301574
TI  - E-cadherin and beta-catenin reduction influence invasion but not proliferation
      and survival in canine malignant mammary tumors.
AB  - E-Cadherin and beta-catenin are known for their role in tumor invasion, but both
      proteins also exert an influence on tumor proliferation. This study, performed on
      canine mammary tumors, aimed to analyze the influence of E-cadherin (E-cad) and
      beta-catenin (beta-cat), immunohistochemically assessed singly and in combination
      (E-cad/beta-cat), on survival and their relationship with several proliferation
      indices (AgNOR index, MIB1 index, mitotic index). Immunohistochemistry was
      carried out on 60 formalin-fixed, paraffin wax-embedded specimens of canine
      mammary malignancies. The labeling was defined as preserved when prevalent on
      cell membranes of more than 75% of cells and reduced in other forms of expression
      (i.e., membranous less than 75%, cytoplasmic, and negative). E-cad, beta-cat, and
      E-cad/beta-cat were preserved respectively in 22, 12, and 11 out of 60 cases.
      Immunohistochemical expression of the two proteins in the same tumors was
      significantly correlated (P = 0.0001; R = 0.57). Survival analysis revealed no
      difference in outcome comparing the preserved versus reduced cases (E-cad, P =
      0.31; beta-cat, P = 0.29; E-cad/beta-cat P = 0.36). Grouping cases for histologic
      invasiveness, the expression of E-cad or beta-cat and E-cad/beta-cat showed a
      progressive reduction that paralleled an increase in invasiveness from
      noninfiltrating to stage-II tumors (E-cad, P < 0.001; beta-cat, P < 0.05; E
      cad/beta-cat, P < 0.05). No significant difference was obtained comparing mitotic
      index, MIB 1 index, and AgNOR index by analysis of variance between the cases
      grouped for preserved or reduced E-cad, beta-cat, and E-cad/beta-cat variables.
      In conclusion, reduced expression of E-cad, beta-cat, or E-cad/beta-cat was
      significantly associated with the progression from noninfiltrating to highly
      infiltrating tumors but not with proliferation or survival.

PMID- 16301575
TI  - Characterization of stages of Hepatozoon americanum and of parasitized canine
      host cells.
AB  - American canine hepatozoonosis is caused by Hepatozoon americanum, a protozoan
      parasite, the definitive host of which is the tick, Amblyomma maculatum.
      Infection of the dog follows ingestion of ticks that harbor sporulated H.
      americanum oocysts. Following penetration of the intestinal mucosa, sporozoites
      are disseminated systemically and give rise to extensive asexual multiplication
      in cells located predominantly in striated muscle. The parasitized canine cells
      in "onion skin" cysts and in granulomas situated within skeletal muscle, as well
      as those in peripheral blood leukocytes (PBL), were identified as macrophages by
      use of fine structure morphology and/or immunohistochemical reactivity with
      macrophage markers. Additionally, two basic morphologic forms of the parasite
      were observed in macrophages of granulomas and PBLs. The forms were presumptively
      identified as merozoites and gamonts. The presence of a "tail" in some gamonts in
      PBLs indicated differentiation toward microgametes. Recognition of merozoites in
      PBLs supports the contention that hematogenously redistributed merozoites
      initiate repeated asexual cycles and could explain persistence of infection for
      long periods in the vertebrate host. Failure to clearly demonstrate a host cell
      membrane defining a parasitophorous vacuole may indicate that the parasite
      actively penetrates the host cell membrane rather than being engulfed by the host
      cell, as is characteristic of some protozoans.

PMID- 16301576
TI  - Histologic features associated with tritrichomonas foetus-induced colitis in
      domestic cats.
AB  - Tritrichomonas foetus is a venereal pathogen of naturally bred cattle. In
      domestic cats, T. foetus colonizes the colon, resulting in chronic, large-bowel
      diarrhea. The infection is prevalent among young, densely housed cats, and there
      is no effective treatment. To the authors' knowledge, the characteristic
      microscopic lesions of T. foetus infection in naturally infected cats have not
      been described. The aim of the study reported here was to characterize the
      histologic changes in the colon of seven cats with T. foetus infection and
      chronic diarrhea. All cats were 1 year old or younger (mean, 6.7 +/- 1.7 months),
      and a diagnosis of T. foetus infection was made on the basis of direct fecal
      smear examination (five cats), fecal culture in InPouch TF medium (four cats),
      single-tube nested polymerase chain reaction (PCR) analysis of DNA extracted from
      feces (two cats), or observation of trichomonads in sections of colon followed by
      PCR confirmation on DNA extracted from paraffin-embedded tissue (two cats). The
      presence of colonic trichomonads was the most diagnostic histologic feature.
      Organisms were identified in all cats, but in only 24 of 43 (56%) sections of
      colon. Trichomonads were generally present in close proximity to the mucosal
      surface and less frequently in the lumen of colonic crypts. The presence of
      colonic trichomonads was consistently associated with mild-to-moderate
      lymphoplasmacytic and neutrophilic colitis, crypt epithelial cell hypertrophy,
      hyperplasia and increased mitotic activity, loss of goblet cells, crypt
      microabscesses, and attenuation of the superficial colonic mucosa. In two of the
      cats, histologic lesions were more severe and were associated with invasion of
      trichomonads into the lamina propria and/or deeper layers of the colon.

PMID- 16301577
TI  - Aberrant p53 expression in feline vaccine-associated sarcomas and correlation
      with prognosis.
AB  - Eighty spontaneously occurring feline vaccine-associated sarcomas (VAS) were
      evaluated to determine the immunohistochemical expression of the tumor suppressor
      gene p53. Sixty-five of 80 VAS (81%) exhibited positive immunoreactivity with
      Mab240, a murine monoclonal antibody that specifically recognizes mutated p53.
      Only 44 of 81 tumors (55%) were positive with rabbit polyclonal antibody CM-1. CM
      1 often yielded nonspecific staining of nonneoplastic tissues. Nonspecific
      staining was greatly reduced or absent with Mab240. Cytoplasmic staining for p53
      was a consistent pattern of VAS, occurring in 44% of tumors evaluated. Cats with
      tumors that exhibited cytoplasmic p53 had significantly shorter time to tumor
      recurrence compared to those cats with tumors that exhibited nuclear p53 staining
      (P = 0.0284), but no significant difference in survival outcome was observed.
      Immunohistochemical detection of p53 offers a prognostic tool for VAS, and,
      because abnormal p53 expression appears to be a common feature of feline VAS,
      molecular targeting of mutant p53, may offer a promising new therapeutic
      opportunity for this cancer.

PMID- 16301578
TI  - Bovine papillomavirus type-2 (BPV-2) infection and expression of uroplakin IIIb,
      a novel urothelial cell marker, in urinary bladder tumors of cows.
AB  - Several immunohistochemical markers have been used to define the differentiation
      pattern of urothelial cell tumors of the urinary bladder. We investigated the
      expression of the recently characterized uroplakin (UP) IIIb, an urothelium
      specific and differentiation-dependent protein, in 39 urothelial tumors of the
      urinary bladder in cows that had suffered from chronic enzootic hematuria for
      several years. Bovine papillomavirus type 2 DNA was amplified and UP IIIb protein
      was detected in all these tumors. In papillomas and papillary carcinomas, UP IIIb
      expression was mostly seen as superficial staining; luminal and peripheral
      patterns were also observed. In nonpapillary carcinomas, UP IIIb appeared to
      define clearly the cell membrane lining intercellular and intracellular lumina as
      well as the cell borders in deeper cell layers. In benign and malignant lesions,
      an intracytoplasmic immunoreactivity was also detected. Coarse intracytoplasmic
      UP IIIb-positive material close to the nucleus occurred in some malignant cells.
      Focally strong membraneous immunostaining that marked single cells with complete
      ringlike peripheral pattern was seen. Although UP IIIb expression does not seem
      to correlate with the biological behavior of urothelial tumors, it appears to be
      a highly sensitive marker for bovine urothelial tumors.

PMID- 16301579
TI  - Extramedullary plasmacytoma of the salivary gland in two Syrian hamsters
      (Mesocricetus auratus).
AB  - Two Syrian hamsters developed marked swelling of the ventral neck. Histologic
      examination of both masses revealed that the submaxillary salivary glands were
      effaced by large numbers of neoplastic plasma cells. In one hamster, neoplastic
      cells had infiltrated the adjacent lymph node. The neoplastic cells expressed
      CD79a antigen and were negative for CD3, lambda, and kappa light chains.
      Ultrastructural features of neoplastic cells in the salivary gland of one hamster
      included abundant cytoplasmic rough endoplasmic reticulum profiles, and
      peripherally displaced nuclei that contained marginated heterochromatin,
      consistent with plasma cells. Salivary gland plasmacytomas are extremely rare in
      humans and have not previously been reported in nonhuman species. The occurrence
      of such neoplasms in two hamsters suggests that this species may be predisposed
      to developing tumors of this type.

PMID- 16301580
TI  - Incidence of polysaccharide storage myopathy: necropsy study of 225 horses.
AB  - Muscle samples were obtained at necropsy from 225 horses and ponies 1 year of age
      or older. Samples were processed in routine manner and were stained with
      hematoxylin and eosin and with periodic acid-Schiff for glycogen. Sections were
      examined for abnormal glycogen content and amylase-resistant complex
      polysaccharide and for chronic myopathic change (excessive fiber size variation,
      increase in number of internal nuclei). A total of 101 horses and ponies with
      lesions of polysaccharide storage myopathy were identified. Age of affected
      horses ranged from one to 30 years, with a mean of 14.7 years. Mean age of
      nonaffected horses was 12 years. Incidence of polysaccharide storage myopathy
      varied depending on breed; Thoroughbreds had the lowest (27%) and draft-related
      horses had the highest (86%) incidence. Chronic myopathic changes were more
      severe in polysaccharide storage myopathy-affected horses than in nonaffected
      horses. Results of this study indicate that polysaccharide storage myopathy is a
      common disorder of many breeds of horses and ponies.

PMID- 16301581
TI  - Canine carcinosarcomas in the head.
AB  - Four cases of neoplasms in the heads of old dogs were studied. All the dogs
      showed both carcinomatous and sarcomatous malignant components in an admixed
      growing pattern. Histologic analysis of the tumors showed that the carcinomatous
      cells resembled squamous cell carcinoma in all dogs except one, where an adenoid
      arrangement of the neoplastic cells was also observed. The sarcomatous component
      showed osteoid matrix produced by pleomorphic poorly differentiated cells, which
      is regarded as a typical feature of osteosarcomas. Immunohistochemical analysis
      demonstrated that the components were positive only for cytokeratin
      (carcinomatous component) or vimentin (sarcomatous component). This observation
      led us to classify the neoplasms as true carcinosarcomas, thus providing evidence
      of a new preferential location for this unusual tumor in dog.

PMID- 16301582
TI  - Primitive neuroectodermal tumor in the spinal cord of a brahman crossbred calf.
AB  - A variety of embryonal tumors of the central nervous system, typically malignant
      and occurring in young individuals, are recognized in humans and animals. This
      report describes an invasive subdural but predominantly extramedullary primitive
      neuroectodermal tumor developing at the lumbosacral junction in a 6-month-old
      Brahman crossbred calf. The tumor was composed of spindloid embryonal cells
      organized in interlacing fascicles. The cells had oval to elongate or round
      hyperchromic nuclei, single to double nucleoli, and scant discernible cytoplasm.
      Immunohistochemical staining for neuron-specific enolase, synaptophysin, and S
      100 protein and formation of pseudorosettes suggested neuronal and possibly
      ependymal differentiation.

PMID- 16301583
TI  - Erythropoietin receptor expression in canine mammary tumor: an
      immunohistochemical study.
AB  - Erythropoietin (EPO) is a cytokine primarily involved in the regulation of the
      erythropoiesis. Recently, it has been demonstrated that EPO and its receptor
      (EPOR) are expressed in several neoplastic cell lines and solid tumors.
      Furthermore, in vitro and in vivo studies have shown that EPO could promote human
      breast carcinoma growth by means of the binding with its receptor, although a
      clear function for EPO in this setting has not been yet established. While the
      human medical literature has been accumulating strong evidence on EPO's role in
      oncogenesis, to date, there are no veterinary reports focusing on such an issue.
      The aim of the present study was to investigate the immunohistochemical
      expression of EPOR in canine mammary gland dysplastic and neoplastic lesions. Our
      results show a weak to moderate EPOR expression in dysplastic glands, being
      immunoreactivity enhanced as the lesion shows an increasing malignant pattern. On
      the basis of these findings, this study describes, for the first time, the
      evidence for EPOR expression in canine mammary gland tumor and suggests a
      feasible EPO's role for canine mammary tumor progression.

PMID- 16301584
TI  - Bacterial meningoencephalitis and ventriculitis due to migrating plant foreign
      bodies in three dogs.
AB  - Regional suppurative meningoencephalitis and ventriculitis of variable chronicity
      was diagnosed in three young dogs residing in Colorado. Grass awns were grossly
      identified in the right occipital cortex of one dog and in the right lateral
      ventricle of another. Intralesional plant material was microscopically evident in
      the dura mater overlying the right occipital cortex of the third dog. One grass
      awn was identified as a floret of Hordeum jabatum. In each case, aerobic culture
      of brain tissue identified multiple isolates of bacteria. The dogs presented with
      clinically variable, rapidly progressive neurologic dysfunction, including
      tetraplegia, depressed mentation, and episodic extensor rigidity, ataxia,
      circling, stupor, vocalization, and head-pressing. Encephalitis due to bacteria
      introduced from migrating plant foreign material is a potential sequela of
      intranasal, periocular, or pharyngeal foreign bodies.

PMID- 16301585
TI  - Second passage of sheep scrapie and transmissible mink encephalopathy (TME)
      agents in raccoons (Procyon lotor).
AB  - To determine the transmissibility and pathogenicity of sheep scrapie and
      transmissible mink encephalopathy (TME) agents derived from raccoons (first
      passage), raccoon kits were inoculated intracerebrally with either TME (one
      source) or scrapie (two sources-each in separate groups of raccoons). Two
      uninoculated raccoon kits served as controls. All animals in the TME-inoculated
      group developed clinical signs of neurologic dysfunction and were euthanatized
      between postinoculation month (PIM) 6 and 8. Raccoons in the two scrapie
      inoculated groups manifested similar clinical signs of disease, but such signs
      were observed much later and the animals were euthanized between PIM 12 and 18.
      Necropsy revealed no gross lesions in any of the raccoons. Spongiform
      encephalopathy was observed by use of light microscopy, and the presence of
      protease-resistant prion protein (PrPres) was detected by use of
      immunohistochemical (IHC) and Western blot analytic techniques. Results of IHC
      analysis indicated a distinct pattern of anatomic distribution of PrPres in the
      TME- and scrapie-inoculated raccoons. These findings confirm that TME and sheep
      scrapie are experimentally transmissible to raccoons and that the incubation
      periods and IHC distribution for both agents are distinct. Therefore, it may be
      possible to use raccoons for differentiating unknown transmissible spongiform
      encephalopathy (TSE) agents. Further studies, with regard to the incubation
      period and the pattern of PrPres deposition by use of IHC analysis in bovine
      spongiform encephalopathy and for other isolates of scrapie, chronic wasting
      disease, and TME in raccoons are needed before the model can be further
      characterized for differentiation of TSE agents.

PMID- 16301586
TI  - Peripheral nerve pathology in two rottweilers with neuronal vacuolation and
      spinocerebellar degeneration.
AB  - Neuronal vacuolation and spinocerebellar degeneration in young Rottweiler dogs is
      a neurodegenerative condition characterized by neuronal vacuolation of several
      nuclei in the central nervous system and degeneration of the spinal cord white
      matter. Here, we describe the morphologic and ultrastructural findings in
      laryngeal muscles and peripheral nerves of a 16-week-old female and a 32-week-old
      female Rottweiler dog affected by progressive ataxia and tetraparesis associated
      with laryngeal paralysis. Lesions were characterized by neurogenic muscle atrophy
      of the intrinsic laryngeal muscles, and a loss of large myelinated fibers in the
      recurrent laryngeal nerve, accompanied by demyelinating/remyelinating features
      affecting the small myelinated fibers. No significant changes were detected in
      the cranial laryngeal, vagus, phrenic, ulnar, or peroneal nerves. These findings
      were indicative of a selective distal neuropathy of the recurrent laryngeal nerve
      with early severe axonal degeneration, mainly of the large myelinated fibers.

PMID- 16301587
TI  - Meningoencephalitis tuberculosa in a holstein cow.
AB  - The gross and histopathologic lesions of meningoencephalitis tuberculosa in a 4
      year-old Holstein cow showing clinical signs compatible with bovine spongiform
      encephalopathy are described in this report. Grossly, numerous gray to yellow,
      firm and caseous nodules were seen on the ventral surfaces of the brain and in
      the lateral and fourth ventricles. Histopathologically, foci of caseation and
      dystrophic mineralization were surrounded by multinucleated giant cells,
      epitheloid macrophages, plasma cells, lymphocytes and fibrous proliferation.
      Ziehl-Neelsen stains of the lesions revealed masses of slender acid-fast bacilli
      in the necrotic centers of lesions and within surrounding giant cells.

PMID- 16301589
TI  - Improving long-term outcomes for patients with liver metastases from colorectal
      cancer.

PMID- 16301590
TI  - Standards for reporting prognostic tumor marker studies.

PMID- 16301591
TI  - Mechanisms of late cardiovascular toxicity from cancer chemotherapy.

PMID- 16301592
TI  - The epothilone dilemma.

PMID- 16301593
TI  - Epidermal growth factor receptor inhibitors in lung cancer: smaller or larger
      molecules, selected or unselected populations?

PMID- 16301594
TI  - Using practice guidelines to assess cancer care quality.

PMID- 16301595
TI  - Phase I dose-finding study of weekly single-agent patupilone in patients with
      advanced solid tumors.
AB  - PURPOSE: To evaluate the safety and maximum-tolerated dose (MTD) of weekly
      patupilone, a natural epothilone B, in patients with advanced solid tumors.
      PATIENTS AND METHODS: Patients were treated with patupilone (0.3 to 3.6 mg/m2)
      for 6 weeks on/3 weeks off or 3 weeks on/1 week off. Dose-limiting toxicities
      (DLTs), MTD, and pharmacokinetics were determined for each schedule of
      administration. RESULTS: Ninety-one patients were enrolled. The most common tumor
      types included ovarian, breast, and colon cancers. Doses of patupilone less than
      2.5 mg/m2 using either the 6 weeks on/3 weeks off or the 3 weeks on/1 week off
      schedule were tolerated well. At higher doses, DLTs were observed using both
      dosing schedules, with diarrhea the most common DLT. The MTD for both treatment
      schedules was 2.5 mg/m2. After a short infusion, patupilone blood concentrations
      declined in a multiphasic manner with a terminal half-life of 4 days. Drug
      clearance was nonrenal and was not related to body-surface area. Over the dose
      range evaluated, systemic drug exposure was approximately dose proportional.
      Three patients achieved a partial response, and 31 patients had stable disease.
      Two patients experiencing a partial response had received prior taxane therapy.
      CONCLUSION: Patupilone is well tolerated when administered at a dose of 2.5
      mg/m2, using either a 6 weeks on/3 weeks off or a 3 weeks on/1 week off schedule.
      In contrast with murine studies, patupilone has a relatively prolonged terminal
      half-life in humans. The partial responses in patients previously treated with
      taxanes is consistent with promising preclinical results.

PMID- 16301596
TI  - Acute chemotherapy-induced cardiovascular changes in patients with testicular
      cancer.
AB  - PURPOSE: After cisplatin- and bleomycin-containing chemotherapy for testicular
      cancer, part of the patient population will develop acute or long-term
      cardiovascular toxicity. It is largely unknown whether standard tests can be used
      to assess chemotherapy-induced cardiovascular changes. PATIENTS AND METHODS: In
      65 testicular cancer patients (median age, 27 years; range, 18 to 48 years), we
      measured the following cardiovascular parameters before and within 10 weeks after
      completion of cisplatin-based chemotherapy: platelet numbers, plasma levels of
      hemostatic and fibrinolytic factors, 24-hour ambulatory blood pressure,
      baroreflex sensitivity, intima-media thickness of the common carotid artery, and
      flow-mediated vasodilation of the brachial artery. RESULTS: Compared with
      prechemotherapy values, the intima-media thickness of the carotid artery and
      plasma von Willebrand factor levels increased significantly after treatment.
      Platelet numbers and plasma levels of other hemostatic and fibrinolytic factors
      did not appear to change significantly. Blood pressure decreased significantly,
      but flow-mediated vasodilation and baroreflex sensitivity did not change.
      CONCLUSION: In testicular cancer patients treated with cisplatin-based
      chemotherapy, we found an increase in plasma von Willebrand factor levels and in
      the intima-media thickness of the carotid artery. These changes may indicate
      chemotherapy-induced vascular damage and be of prognostic significance for the
      development of cardiovascular complications in the long term.

PMID- 16301597
TI  - Phase I/IIa study of cetuximab with gemcitabine plus carboplatin in patients with
      chemotherapy-naive advanced non-small-cell lung cancer.
AB  - PURPOSE: This multicenter, open-label, phase I/IIa study was undertaken to
      establish the safety/toxicity profile of cetuximab in combination with
      gemcitabine and carboplatin in patients with chemotherapy-naive, epidermal growth
      factor receptor-positive, stage IV non-small-cell lung cancer. Secondary
      objectives were to gather preliminary evidence of efficacy including tumor
      response rate, time to progression, and overall survival. PATIENTS AND METHODS:
      Thirty-five patients received a total of 264 3-week cycles of treatment with
      cetuximab, carboplatin, and gemcitabine. An initial dose of cetuximab 400 mg/m2
      intravenously was administered the first week, followed by weekly doses of 250
      mg/m2. Carboplatin (area under the curve = 5, day 1) and gemcitabine 1,000 mg/m2
      on days 1 and 8 were administered every 3 weeks. Patients were evaluated for
      tumor response after every two cycles of therapy. RESULTS: The most frequently
      reported adverse events related to cetuximab included an acne-like rash (88.6%),
      dry skin (34.3%), asthenia and skin disorders (31.4%), mucositis/stomatitis
      (25.7%), fever/chills (20%), and nausea/vomiting (17.1%). The majority of these
      toxicities were mild to moderate. One patient withdrew from the study because of
      a grade 3 allergic reaction. Myelosuppression was the most frequently observed
      toxicity related to chemotherapy. Responses among 35 assessable patients included
      10 partial responses (28.6%). Twenty-one patients had stable disease. The median
      time to progression was 165 days, and the median overall survival was 310 days.
      CONCLUSION: The combination of cetuximab, carboplatin, and gemcitabine was well
      tolerated with an acceptable toxicity profile. Most grade 3 adverse events were
      attributable to chemotherapy. The response rate and median survival are
      encouraging and warrant additional investigation.

PMID- 16301598
TI  - Insurance status and the use of guideline therapy in the treatment of selected
      cancers.
AB  - PURPOSE: This study estimates the impact of type of insurance coverage on the
      receipt of guideline therapy in a population-based sample of cancer patients
      treated in the community. PATIENTS AND METHODS: Patients (n = 7,134) from the
      National Cancer Institute's Patterns of Care studies who were newly diagnosed
      with 11 different types of cancer were analyzed. The definition of guideline
      therapy was based on the National Comprehensive Cancer Network treatment
      recommendations. Insurance status was categorized as a mutually exclusive
      hierarchical variable (no insurance, any private insurance, any Medicaid,
      Medicare only, and all other). Multivariate analyses were used to examine the
      association between insurance and receipt of guideline therapy. RESULTS:
      Adjusting for clinical and nonclinical variables, insurance status was a modest,
      although statistically significant, determinant of receipt of guideline therapy,
      with 65% of the privately insured patients receiving recommended therapy compared
      with 60% of patients with Medicaid. Seventy percent of the uninsured patients
      received guideline therapy, which was nonsignificantly different compared with
      private insurance. When stratified by race, insurance was a statistically
      significant predictor of the receipt of guideline therapy only for non-Hispanic
      blacks. CONCLUSION: Overall, levels of guideline treatment were lower than
      expected and particularly low for patients with Medicaid or Medicare only. The
      use of guideline therapy for ovarian and cervical cancer patients and for
      patients with rectal cancers was unrelated to type of insurance. Of particular
      concern is the significantly lower use of guideline therapy for non-Hispanic
      black patients with Medicaid. After adjusting for other factors, only half of
      these patients received guideline therapy.

PMID- 16301599
TI  - A yeast RNA-hybrid system for the detection of RNA-RNA interactions in vivo.
AB  - RNA-RNA interactions play a crucial role at many different levels of the cellular
      metabolism such as plasmid replication control, viral encapsidation, or
      transcriptional and translational regulation. Therefore, methods are necessary to
      investigate the molecular determinants of given interactions, including their
      stabilities, or to screen for new interacting partners. We designed an RNA-hybrid
      system in S. cerevisiae, based on the yeast three-hybrid system. In this setup,
      the activation of a reporter gene is dependent on the interaction of two RNAs. A
      loop-loop interaction similar to the dimerization initiation site of the HIV
      genome was used as a model system, demonstrating that in this novel RNA-hybrid
      system only cognate RNAs promote the activation of the reporter gene. Levels of
      reporter activation correlate well with interaction stabilities determined in
      vitro by UV melting analyses, suggesting that conditions used for the analysis of
      in vitro structural stabilities translate well into the intracellular
      environment. Furthermore, the system was applicable for a screen against a test
      library. Nine out of ten selected clones were identified as predicted interaction
      partners for the bait RNA. In summary, we present a yeast reporter system
      depending on RNA-RNA interactions, which can be used alternatively for analysis
      of known interactions or for screening libraries in search for new interaction
      partners.

PMID- 16301600
TI  - A base-specific recognition signal in the 5' consensus sequence of rotavirus plus
      strand RNAs promotes replication of the double-stranded RNA genome segments.
AB  - Replication of the segmented double-stranded (ds)RNA genome of rotavirus requires
      the viral RNA-dependent RNA polymerase (RdRP) to use 11 different (+)RNAs as
      templates for (-) strand synthesis. Complementary sequences proximal to the 5'
      and 3' termini are predicted to direct cyclization of the (+)RNAs by forming
      panhandle structures from which short highly conserved terminal sequences
      protrude as single-stranded tails. Cell-free replication assays indicate that
      such structural organization of the 5'- and 3'-ends is required for efficient
      dsRNA synthesis. Multiple specifically recognized elements exist at the 3'-end
      that promote dsRNA synthesis including RdRP-recruitment signals and a (-) strand
      initiation sequence. In contrast to the 3'-end, the role of the 5'-end has been
      less well defined. In this study, we determined that the 5'-end contains a base
      specific recognition signal that plays an important role in the assembly of the
      RdRP and cofactors into a stable initiation complex for (-) strand synthesis. The
      5' recognition signal is associated with the G2 residue of the 5'-consensus
      sequence, a residue that shows absolute conservation among all rotavirus groups
      (A, B, and C) examined to date. From our results, we suggest that rotavirus
      (+)RNA cyclization, although likely initiated by 5'- 3' nucleotide
      complementarity, may be stabilized by RdRP-dependent bridging. Given that
      synthesis of the (-) strand on the (+)RNA template will disrupt 5'-3' nucleotide
      interactions, RdRP-dependent bridging may be the sole mechanism by which the
      dsRNA product can be held in the necessary cyclized conformation required for
      efficient multiple rounds of transcription.

PMID- 16301601
TI  - A 3' UTR sequence stabilizes termination codons in the unspliced RNA of Rous
      sarcoma virus.
AB  - Eukaryotic cells target mRNAs to the nonsense-mediated mRNA decay (NMD) pathway
      when translation terminates within the coding region. In mammalian cells, this is
      presumably due to a downstream signal deposited during pre-mRNA splicing. In
      contrast, unspliced retroviral RNA undergoes NMD in chicken cells when premature
      termination codons (PTCs) are present in the gag gene. Surprisingly, deletion of
      a 401-nt 3' UTR sequence immediately downstream of the normal gag termination
      codon caused this termination event to be recognized as premature. We termed this
      3' UTR region the Rous sarcoma virus (RSV) stability element (RSE). The RSE also
      stabilized the viral RNA when placed immediately downstream of a PTC in the gag
      gene. Deletion analysis of the RSE indicated a smaller functional element. We
      conclude that this 3' UTR sequence stabilizes termination codons in the RSV RNA,
      and termination codons not associated with such an RSE sequence undergo NMD.

PMID- 16301602
TI  - Small interfering RNAs containing full 2'-O-methylribonucleotide-modified sense
      strands display Argonaute2/eIF2C2-dependent activity.
AB  - RNA interference (RNAi) is a process by which short interfering RNAs (siRNAs)
      direct the degradation of complementary single-strand RNAs. In this study, we
      investigated the effects of full-strand phosphorothioate (PS) backbone and 2'-O
      methyl (2'-OMe) sugar modifications on RNAi-mediated silencing. In contrast to
      previous reports, we have identified active siRNA duplexes containing full 2'-OMe
      modified sense strands that display comparable activity to the unmodified analog
      of similar sequence. The structure of these modified siRNAs is the predominant
      determinant of their activity, with sequence and backbone composition being
      secondary. We further show, by using biotin-tagged siRNAs and affinity-tagged
      hAgo2/eIF2C2, that activity of siRNA duplexes containing full 2'-OMe
      substitutions in the sense strand is mediated by the RNA-induced silencing
      complex (RISC) and that strand-specific loading (or binding) to hAgo2 may be
      modulated through selective incorporation of these modifications.

PMID- 16301603
TI  - Conformational changes involved in initiation of minus-strand synthesis of a
      virus-associated RNA.
AB  - Synthesis of wild-type levels of turnip crinkle virus (TCV)-associated satC
      complementary strands by purified, recombinant TCV RNA-dependent RNA polymerase
      (RdRp) in vitro was previously determined to require 3' end pairing to the large
      symmetrical internal loop of a phylogenetically conserved hairpin (H5) located
      upstream from the hairpin core promoter. However, wild-type satC transcripts,
      which fold into a single detectable conformation in vitro as determined by
      temperature-gradient gel electrophoresis, do not contain either the
      phylogenetically inferred H5 structure or the 3' end/H5 interaction. This implies
      that conformational changes are required to produce the phylogenetically inferred
      H5 structure for its pairing with the 3' end, which takes place subsequent to the
      initial conformation assumed by the RNA and prior to transcription initiation.
      The DR region, located 140 nucleotides upstream from the 3' end and previously
      determined to be important for transcription in vitro and replication in vivo, is
      proposed to have a role in the conformational switch, since stabilizing the
      phylogenetically inferred H5 structure decreases the negative effects of a DR
      mutation in vivo. In addition, high levels of aberrant transcription correlate
      with a specific conformational change in the Pr while maintaining the same
      conformation of the 3' terminus. These results suggest that a series of events
      that promote conformational changes is needed to expose the 3' terminus to the
      RdRp for accurate synthesis of wild-type levels of complementary strands in
      vitro.

PMID- 16301604
TI  - Effective inhibition of human cytomegalovirus gene expression and growth by
      intracellular expression of external guide sequence RNA.
AB  - RNase P complexed with external guide sequence (EGS) represents a novel nucleic
      acid-based gene interference approach to modulate gene expression. In this study,
      a functional EGS RNA was constructed to target the overlapping mRNA region of two
      human cytomegalovirus (HCMV) capsid proteins, the capsid scaffolding protein
      (CSP) and assemblin. The EGS RNA was shown to be able to direct human RNase P to
      cleave the target mRNA sequence efficiently in vitro. A reduction of
      approximately 75%-80% in the mRNA and protein expression levels of both CSP and
      assemblin and a reduction of 800-fold in viral growth were observed in human
      cells that expressed the functional EGS, but not in cells that either did not
      express the EGS or produced a "disabled" EGS that carried nucleotide mutations
      that precluded RNase P recognition. The action of the EGS is specific as the
      RNase P-mediated cleavage only reduces the expression of the CSP and assemblin
      but not other viral genes examined. Further studies of the antiviral effects of
      the EGS indicate that the expression of the functional EGS has no effect on HCMV
      genome replication but blocks viral capsid maturation, consistent with the notion
      that CSP and assemblin play essential roles in HCMV capsid formation. Our study
      provides the first direct evidence that EGS RNAs effectively inhibit HCMV gene
      expression and growth. Moreover, these results demonstrate the utility of EGS
      RNAs in gene therapy applications, including the treatment of HCMV infection by
      inhibiting the expression of virus-encoded essential proteins.

PMID- 16301605
TI  - Mechanism of the phosphatase component of Clostridium thermocellum polynucleotide
      kinase-phosphatase.
AB  - Polynucleotide kinase-phosphatase (Pnkp) from Clostridium thermocellum catalyzes
      ATP-dependent phosphorylation of 5'-OH termini of DNA or RNA polynucleotides and
      Ni(2+)/Mn(2+)-dependent dephosphorylation of 2',3' cyclic phosphate, 2'
      phosphate, and 3'-phosphate ribonucleotides. CthPnkp is an 870-amino-acid
      polypeptide composed of three domains: an N-terminal module similar to
      bacteriophage T4 polynucleotide kinase, a central module that resembles the
      dinuclear metallo-phosphoesterase superfamily, and a C-terminal ligase-like
      adenylyltransferase domain. Here we conducted a mutational analysis of CthPnkp
      that identified 11 residues required for Ni(2+)-dependent phosphatase activity
      with 2'-AMP and 3'-AMP. Eight of the 11 CthPnkp side chains were also required
      for Ni(2+)-dependent hydrolysis of p-nitrophenyl phosphate. The ensemble of
      essential side chains includes the conserved counterparts (Asp187, His189,
      Asp233, Arg237, Asn263, His264, His323, His376, and Asp392 in CthPnkp) of all of
      the amino acids that form the dinuclear metal-binding site and the phosphate
      binding site of bacteriophage lambda phosphatase. Three residues (Asp236, His264,
      and Arg237) required for activity with 2'-AMP or 3'-AMP were dispensable for
      Ni(2+)-dependent hydrolysis of p-nitrophenyl phosphate. Our findings, together
      with available structural information, provide fresh insights to the
      metallophosphoesterase mechanism, including the roles of His264 and Asp236 in
      proton donation to the leaving group. Deletion analysis defined an autonomous
      phosphatase domain, CthPnkp-(171-424).

PMID- 16301607
TI  - Shaping the T cell repertoire.

PMID- 16301606
TI  - A protein related to the vaccinia virus cap-specific methyltransferase VP39 is
      involved in cap 4 modification in Trypanosoma brucei.
AB  - The spliced-leader (SL) RNA plays a key role in the biogenesis of mRNA in
      trypanosomes by providing the m(7)G-capped SL sequence to the 5' end of every
      mRNA. The cap structure of the SL RNA is unique in eukaryotes with 4 nucleotides
      after the cap carrying a total of seven methyl groups and by convention is
      referred to as "cap 4". Although the enzymatic machinery for cap addition has
      been characterized in several organisms, including Trypanosoma brucei, the
      identification of methyltransferases dedicated to the generation of higher order
      cap structures has lagged behind, except in viruses. Here we describe T. brucei
      MT57 (TbMT57), a primarily nuclear polypeptide with structural and functional
      similarities to vaccinia virus VP39, a bifunctional protein acting at the mRNA 5'
      end as a cap-specific 2'-O-methyltransferase. Down-regulation by RNAi or genetic
      ablation of TbMT57 resulted in the accumulation of SL RNA missing 2'-O-methyl
      groups at positions +3 and +4 and thus bearing a cap 2 rather than a cap 4.
      Furthermore, competitive binding studies indicated that modifications at the +3
      and +4 positions are important for binding to the nuclear cap-binding complex.
      Genetic ablation of MT57 resulted in viable cells with no apparent defect in SL
      RNA trans-splicing, suggesting that MT57 is not essential or that trypanosomes
      have developed alternate mechanisms to counteract the absence of this protein.
      Interestingly, MT57 homologs are only found in trypanosomatid protozoa that have
      a cap 4 structure and in poxviruses, of which vaccinia virus is a prototype.

PMID- 16301608
TI  - The major histocompatibility complex determines susceptibility to cytotoxic T
      cells directed against minor histocompatibility antigens. 1975.

PMID- 16301609
TI  - Granulocyte colony-stimulating factor: a novel mediator of T cell tolerance.
AB  - In recent years, several investigators have unraveled a previously unrecognized
      role for G-CSF in the regulation of T cell and dendritic cell functions. The
      experimental evidence in favor of G-CSF-mediated immune regulation includes the
      ability to switch T cell cytokine secretion profile to Th2 responses and the
      promotion of regulatory T cell and tolerogenic dendritic cell differentiation.
      Interestingly, G-CSF is beneficial in animals for the prevention and/or treatment
      of immune-mediated diseases, e.g., graft-vs-host disease, multiple sclerosis,
      systemic lupus erythematosus, inflammatory bowel disease, and diabetes,
      suggesting a potential role in human autoimmune diseases. This review summarizes
      the growing body of evidence that supports a critical role for G-CSF as a novel
      mediator of T cell tolerance.

PMID- 16301610
TI  - Cutting edge: CD8+CD122+ regulatory T cells produce IL-10 to suppress IFN-gamma
      production and proliferation of CD8+ T cells.
AB  - We recently identified CD8+CD122+ regulatory T cells that directly control CD8+
      and CD4+ cells without intervention of APCs. In this study, we investigated the
      effector mechanism of CD8+CD122+ regulatory T cells by using an in vitro
      regulation system. The profile of cytokine expression revealed that IL-10 was
      predominantly produced by CD8+CD122+ cells, whereas other cytokines were
      similarly expressed in CD8+CD122+ cells and CD8+CD122- cells. Suppression of both
      proliferation and IFN-gamma production by CD8+CD122- cells by CD8+CD122+ cells
      was blocked by adding anti-IL-10 Ab to the culture but not by adding anti-TGF
      beta Ab. When IL-10 was removed from the conditioned medium from CD8+CD122+
      cells, the conditioned medium no longer showed regulatory activity. Finally,
      CD8+CD122+ cells from IL-10-deficient mice had no regulatory activity in vitro
      and reduced regulatory activity in vivo. Our results clearly indicate that IL-10
      is produced by CD8+CD122+ cells and mediates the regulatory activity of these
      cells.

PMID- 16301611
TI  - Cutting edge: murine CD59a modulates antiviral CD4+ T cell activity in a
      complement-independent manner.
AB  - CD59 blocks formation of the membrane attack complex of complement by inhibiting
      binding of C9 to the C5b-8 complex. To investigate a role for CD59 in promoting T
      cell responses, we compared T cell activation in CD59a-deficient (Cd59a-/-) and
      wild-type (WT) mice after in vitro stimulation and after infection with rVV.
      Virus-specific CD4+ T cell responses were significantly enhanced in Cd59a-/- mice
      compared with WT mice. Similarly, Cd59a-/- T cells responded more vigorously to
      in vitro stimulation with CD3-specific Abs compared with WT mice. This effect of
      CD59a on T cell proliferation was found to be complement-independent.
      Collectively, these results demonstrate that CD59a down-modulates CD4+ T cell
      activity in vitro and in vivo, thereby revealing another link between complement
      regulators and T cell activation.

PMID- 16301612
TI  - Cutting edge: the development of IL-4-producing B cells (B effector 2 cells) is
      controlled by IL-4, IL-4 receptor alpha, and Th2 cells.
AB  - Although IL-4-producing B cells (B effector 2 cells) are found following
      infection and immunization, the signals regulating IL-4 production by Be2 cells
      are unknown. We show that culturing naive B cells with Th2 cells induces up
      regulation of IL-4 in the B cells with a concomitant down-regulation of T-bet, IL
      12Rbeta2, and IFN-gamma. Up-regulation of IL-4 in the Be2 cells is dependent on
      both T cells and IL-4 as IL-4Ralpha-deficient B cells primed with Th2 cells did
      not transcribe IL-4, and B cells primed in the presence of IL-4-deficient Th2
      cells produced IFN-gamma instead of IL-4. Likewise, the in vivo development of IL
      4-expressing B cells in a nematode infection model was dependent on both T cells
      and IL-4Ralpha-mediated signals. Thus, the differentiation of naive B cells into
      IL-4-expressing Be2 cells is regulated by a combination of T cell-dependent
      signals and the cytokine environment and this process is critically dependent
      upon the IL-4/IL-4R signaling pathway.

PMID- 16301613
TI  - CXCR5-dependent seeding of follicular niches by B and Th cells augments antiviral
      B cell responses.
AB  - The chemokine receptor CXCR5 and its ligand CXCL13 define the structure of B cell
      follicles within secondary lymphoid organs. Here, we examined the impact of CXCR5
      on antiviral B cell responses in vivo. CXCR5-/- mice showed a normal production
      of IgM and IgG acutely after infection with vesicular stomatitis virus (VSV) and
      developed VSV-specific germinal centers. However, impaired Ig class switch and Ab
      production were observed under conditions of limited availability of Ag (i.e.,
      after immunization with nonreplicating viral particles or soluble Ag). Adoptive
      transfer of CXCR5-deficient, VSV-specific B and Th cells demonstrated that CXCR5
      expression on both B and Th cells is required for an efficient Ig class switch.
      These experiments revealed that CXCR5 is critical for the coordinated interaction
      of antiviral T and B cells through its impact on initial B cell expansion and the
      recruitment of Ag-specific B and Th cells to germinal centers.

PMID- 16301614
TI  - Modulation of ovalbumin-induced airway inflammation and hyperreactivity by
      tolerogenic APC.
AB  - Allergic asthma is mediated in part by unregulated Th2 inflammation in response
      to an allergen. Induction of peripheral tolerance by inoculation of Ags into the
      anterior chamber of the eye (ocular tolerance) before sensitization blocks Th2
      responses. Thus, we proposed that induction of ocular tolerance to the allergen
      might modulate an ongoing allergen-induced Th2 pathogenesis in the lung. We
      initiated ocular tolerance in previously immunized mice in a classic mouse model
      of OVA-induced pulmonary allergic inflammation. In the model of ocular tolerance,
      the need for inoculation of Ag into the anterior chamber can be bypassed by i.v.
      inoculation of in vitro-generated tolerogenic (TGF-beta2-treated, Ag-pulsed) APC
      (tol-APC). We observed that with i.v. inoculation, such tolerogenic APC, but not
      control APC, reduced eosinophil and lymphocyte pulmonary infiltration in
      experimental mice. Similarly, production of Th2 cytokines (IL-4, -5, and -13),
      but not IFN-gamma, was reduced. Importantly, airway hyperresponsiveness and mucus
      production were significantly reduced after treatment with the tol-APC. We also
      show that in vitro suppression of IL-13 production from OVA-sensitized effector T
      cells was mediated by CD8+, not CD4+, T regulatory cells. Thus, i.v. inoculation
      of the tol-APC induced peripheral tolerance that suppressed Th2-mediated
      pathogenesis in the lungs of presensitized mice. The ability of the tol-APC to
      induce peripheral tolerance and suppress existing Th2 immune inflammation may
      lead to novel therapies for pulmonary allergic inflammation and its related
      pathology.

PMID- 16301615
TI  - B cells productively engage soluble antigen-pulsed dendritic cells: visualization
      of live-cell dynamics of B cell-dendritic cell interactions.
AB  - Interactions between B lymphocytes and Ag-bearing dendritic cells (DC) likely
      occur at inflammatory sites and within lymphoid organs. To better understand
      these interactions we imaged B cells (TgB) from hen egg lysozyme (HEL) transgenic
      mice and DC pulsed with HEL (DC-HEL) in collagen matrices. Analysis of live-cell
      dynamics revealed autonomous movements and repeated encounters between TgB cells
      and DC-HEL that are best described by a "kiss-run and engage" model, whereas
      control B cells had only short-lived interactions. Ag localized at contact sites
      between TgB cells and DC-HEL, and both cell types rearranged their actin
      cytoskeletons toward the contact zone. The interaction of a TgB cell with a HEL
      bearing DC triggered strong Ca2+ transients in the B cells. Thus, B cells can
      productively interact with DC displaying their cognate Ag.

PMID- 16301616
TI  - CD4+CD25+ T cells prevent the development of organ-specific autoimmune disease by
      inhibiting the differentiation of autoreactive effector T cells.
AB  - Thymic-derived, naturally occurring, CD4+CD25+ regulatory T cells (nTreg) are
      potent suppressors of immune responses. A detailed understanding of which
      components of the development and activation of pathogenic effector T cells are
      inhibited by nTreg during the course of T cell-mediated, organ-specific
      autoimmunity is as yet unknown. We have analyzed the effects of polyclonal nTreg
      on the development of autoimmune gastritis. The nTreg inhibited the development
      of disease, but failed to inhibit the migration of effector cells into the
      gastric lymph node or stomach. Notably, nTreg did not inhibit the expansion of
      autoreactive T cells in the gastric lymph node. The primary effect of nTreg
      appeared to be inhibition of differentiation of autoantigen-specific T cells to
      Th1 effector cells, as reflected by a decrease in Ag-stimulated IFN-gamma
      production and a reduction in T-bet expression.

PMID- 16301617
TI  - STAT4 expression in human T cells is regulated by DNA methylation but not by
      promoter polymorphism.
AB  - STAT4, which plays a pivotal role in Th1 immune responses, enhances IFN-gamma
      transcription in response to the interaction of IL-12 with the IL-12R. Mice
      deficient in STAT4 lack IL-12-induced IFN-gamma production and Th1
      differentiation and display a predominantly Th2 phenotype. Although these
      findings indicate that STAT4 expression levels are important for the development
      of cytokine-producing Th1 cells, the transcriptional and posttranscriptional
      mechanisms regulating STAT4 expression are unknown. We sought to identify and
      characterize the transcriptional regulatory elements in the promoter region of
      the human STAT4 gene. We found that disruption of multiple transcriptional
      regions covering the CREB, OCT1, and SP1 motifs significantly reduced STAT4
      promoter activity. However, genomic DNA isolated from 91 patients with asthma or
      rheumatoid arthritis showed no evidence of mutations in the defined STAT4
      essential promoter region. The 5' flanking region of the promoter was found to
      contain a -149A/G change in approximately 20-35% of patients, but this
      polymorphism had no effect on promoter activity. Interestingly, STAT4 expression
      was drastically increased in human T cells following treatment with a DNA
      methyltransferase inhibitor, and truncation of methylation sites in the proximal
      regulatory elements of the STAT4 promoter markedly enhanced transcriptional
      activity. Thus, our findings provide molecular insight into STAT4 expression and
      suggest that, in human T cells, STAT4 expressional regulation is associated with
      DNA hypermethylation, but not promoter polymorphisms.

PMID- 16301618
TI  - Sphingosine-1-phosphate agonists increase macrophage homing, lymphocyte contacts,
      and endothelial junctional complex formation in murine lymph nodes.
AB  - The sphingosine-1-phosphate (S1P) receptor agonist, phosphorylated FTY720 (FTY
      P), causes lymphopenia, lymphocyte sequestration in mesenteric lymph nodes
      (MLNs), and immunosuppression. Using multiple techniques to analyze MLN cells
      harvested from mice treated with S1P receptor agonists, we saw a redistribution
      of lymphocytes out of nodal sinuses and an expansion of follicles. Although
      changes in circulating monocytes were not observed with overnight exposure to
      FTY720, we saw a significant increase in S1P receptor 1 (S1P1)-expressing CD68+
      macrophages in subcapsular sinuses of FTY-P-treated MLNs. This was confirmed by
      quantitative analysis of F4/80+ cells in MLN suspensions. The sinus volume and
      number of S1P1-positive cells within sinuses were also increased by FTY-P. High
      endothelial venules and lymphatic endothelium expressed high levels of S1P1, and
      treatment with FTY-P resulted in intense staining and colocalization of CD31,
      beta-catenin, and zona occludens 1 in junctions between sinus cells. Transmission
      electron microscopy showed that FTY-P greatly reduced lymphocyte microvilli and
      increased cell-cell contacts in the parenchyma. Immunoelectron microscopy
      revealed that intranodal lymphocytes lacked surface expression of S1P1, whereas
      S1P1 was evident on the surface and within the cytoplasm of macrophages,
      endothelial cells, and stromal cells. This subcellular pattern of intranodal
      receptor distribution was unchanged by treatment with FTY-P. We conclude that
      S1P1 agonists have profound effects on macrophages and endothelial cells, in
      addition to inducing lymphopenia.

PMID- 16301619
TI  - Helicobacter pylori activates NF-kappaB via the alternative pathway in B
      lymphocytes.
AB  - Helicobacter pylori causes various gastroduodenal diseases including gastric MALT
      lymphoma, but the mechanism underlying H. pylori-induced carcinogenesis is not
      known. The alternative pathway for NF-kappaB activation, which involves the
      processing of NF-kappaB2/p100 to p52, has been implicated in lymphocyte survival,
      attenuated apoptosis, and secondary lymphoid tissue development. In this study,
      we investigated H. pylori-induced activation of NF-kappaB through the alternative
      pathway in B lymphocytes. In immunoblot and EMSA, H. pylori induced NF
      kappaB2/p100 processing to p52 and subsequent nuclear accumulation in IM-9 (human
      B cell line) cells and human peripheral blood B cells, but not in AGS (human
      gastric cancer cell line) cells. The activation of the alternative pathway was
      LPS-dependent but not cag pathogenicity island-dependent. Alternative pathway
      activation by H. pylori was associated with attenuated apoptosis. The expression
      levels of B lymphocyte chemoattractant, EBI-1 ligand chemokine, and stromal cell
      derived factor-1alpha mRNAs were up-regulated in cocultured human B cells and in
      infected human gastric mucosa. In the infected mucosa, NF-kappaB2/p100 and p52
      were detected immunohistochemically in the cytoplasm and nuclear compartments of
      lymphocytes, but not in epithelial cells. In summary, H. pylori activates the
      alternative NF-kappaB pathway in B lymphocytes. The effects on chemokine
      production and antiapoptosis mediated by H. pylori-induced processing of NF
      kappaB2/p100 to p52 may drive lymphocytes to acquire malignant potential.

PMID- 16301620
TI  - An hour after immunization peritoneal B-1 cells are activated to migrate to
      lymphoid organs where within 1 day they produce IgM antibodies that initiate
      elicitation of contact sensitivity.
AB  - Elicitation of contact sensitivity (CS), a classic example of T cell-mediated
      immunity, requires Ag-specific IgM Abs to trigger an initiation process. This
      early process leads to local recruitment of CS-effector T cells after secondary
      Ag challenge. These Abs are produced by the B-1 subset of B cells within 1 day
      after primary skin immunization. In this study we report the surprising
      observation that B-1 cells in the peritoneal cavity are activated as early as 1 h
      after naive mice are painted with a contact-sensitizing Ag on the skin of the
      trunk and feet to begin the initiation of CS. B-1 cells in the spleen and
      draining lymph nodes produce the initiating Abs by 1 day after immunization, when
      we found increased numbers of Ag-specific IgM Ab-producing cells in these tissues
      by ELISPOT assay. Importantly, we show that contact-activated peritoneal B-1
      cells migrate to these lymphoid tissues and then differentiate into Ag-specific
      IgM Ab-producing cells, resulting in specific CS-initiating IgM Abs in the serum
      by 1 day. Furthermore, pertussis toxin, which is known to inhibit signaling via G
      protein-coupled chemokines, inhibited the migration of contact-activated
      peritoneal B-1 cells to the lymphoid tissues, probably due to BLR-1 (Burkitt
      lymphoma receptor-1). These findings indicate that within 1 h after contact skin
      immunization, B-1 cells in the peritoneal cavity are activated to migrate to the
      lymphoid tissues by chemokine-dependent mechanisms to produce serum Ag-specific
      IgM Abs within 1 day after immunization, leading to local recruitment of CS
      effector T cells.

PMID- 16301621
TI  - RasGRP1 and RasGRP3 regulate B cell proliferation by facilitating B cell receptor
      Ras signaling.
AB  - The RasGRPs are a family of Ras activators that possess diacylglycerol-binding C1
      domains. In T cells, RasGRP1 links TCR signaling to Ras. B cells coexpress
      RasGRP1 and RasGRP3. Using Rasgrp1 and Rasgrp3 single and double null mutant
      mice, we analyzed the role of these proteins in signaling to Ras and Erk in B
      cells. RasGRP1 and RasGRP3 both contribute to BCR-induced Ras activation,
      although RasGRP3 alone is responsible for maintaining basal Ras-GTP levels in
      unstimulated cells. Surprisingly, RasGRP-mediated Ras activation is not essential
      for B cell development because this process occurs normally in double-mutant
      mice. However, RasGRP-deficient mice do exhibit humoral defects. Loss of RasGRP3
      led to isotype-specific deficiencies in Ab induction in immunized young mice. As
      reported previously, older Rasgrp1-/- mice develop splenomegaly and antinuclear
      Abs as a result of a T cell defect. We find that such mice have elevated serum Ig
      levels of several isotypes. In contrast, Rasgrp3-/- mice exhibit
      hypogammaglobulinemia and show no signs of splenomegaly or autoimmunity. Double
      mutant mice exhibit intermediate serum Ab titers, albeit higher than wild-type
      mice. Remarkably, double-mutant mice exhibit no signs of autoimmunity or
      splenomegaly. B cell proliferation induced by BCR ligation with or without IL-4
      was found to be RasGRP1- and RasGRP3-dependent. However, the RasGRPs are not
      required for B cell proliferation per se, because LPS-induced proliferation is
      unaffected in double-mutant mice.

PMID- 16301622
TI  - Membranous glomerulonephritis development with Th2-type immune deviations in
      MRL/lpr mice deficient for IL-27 receptor (WSX-1).
AB  - MRL/lpr mice develop spontaneous glomerulonephritis that is essentially identical
      with diffuse proliferative glomerulonephritis (World Health Organization class
      IV) in human lupus nephritis. Lupus nephritis is one of the most serious
      complications of systemic lupus erythematosus. Diffuse proliferative
      glomerulonephritis is associated with autoimmune responses dominated by Th1 cells
      producing high levels of IFN-gamma. The initial mounting of Th1 responses depends
      on the function of the WSX-1 gene, which encodes a subunit of the IL-27R with
      homology to IL-12R. In mice deficient for the WSX-1 gene, proper Th1
      differentiation was impaired and abnormal Th2 skewing was observed during
      infection with some intracellular pathogens. Disruption of the WSX-1 gene
      dramatically changed the pathophysiology of glomerulonephritis developing in
      MRL/lpr mice. WSX-1-/- MRL/lpr mice developed disease resembling human membranous
      glomerulonephritis (World Health Organization class V) with a predominance of
      IgG1 in glomerular deposits, accompanied by increased IgG1 and IgE in the sera. T
      cells in WSX-1-/- MRL/lpr mice displayed significantly reduced IFN-gamma
      production along with elevated IL-4 expression. Loss of WSX-1 thus favors Th2
      type autoimmune responses, suggesting that the Th1/Th2 balance may be a pivotal
      determinant of human lupus nephritis development.

PMID- 16301623
TI  - Interaction of Fas ligand and Fas expressed on osteoclast precursors increases
      osteoclastogenesis.
AB  - We incidentally found that osteoclast precursors and mature osteoclasts express
      Fas ligand (FasL) as well as Fas, which was confirmed by flow cytometry,
      immunofluorescent staining, and RT-PCR. The aim of this study was to determine
      the role of FasL in differentiation and cell death of osteoclasts. To study the
      role of FasL in osteoclastogenesis, neutralizing anti-FasL mAb or rFasL was added
      during receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis
      using bone marrow-derived macrophages. Neutralization of endogenous FasL by anti
      FasL mAb decreased osteoclastogenesis, whereas rFasL enhanced osteoclast
      differentiation in a dose-dependent manner. In addition, rFasL up-regulated the
      secretion of osteoclastogenic cytokines, such as IL-1beta and TNF-alpha, and the
      activation of NF-kappaB. Functional blocking of IL-1beta and TNF-alpha using IL-1
      receptor antagonist and soluble TNFR confirmed that those cytokines mediated the
      effect of FasL on osteoclastogenesis. The osteoclast precursors were relatively
      resistant to rFasL-induced apoptosis especially before RANKL treatment, resulting
      in minimal cell loss by rFasL treatment during osteoclastogenesis. Although rFasL
      increased the cell death of mature osteoclasts, growth factor withdrawal induced
      much more cell death. However, anti-FasL mAb did not affect the survival of
      mature osteoclasts, suggesting that the endogenous FasL does not have a role in
      the apoptosis of osteoclasts. Finally, in contrast to the effect on apoptosis,
      rFasL-assisted osteoclastogenesis was not mediated by caspases. In conclusion,
      FasL has a novel function in bone homeostasis by enhancing the differentiation of
      osteoclasts, which was not considered previously.

PMID- 16301624
TI  - Glucosamine abrogates the acute phase of experimental autoimmune
      encephalomyelitis by induction of Th2 response.
AB  - Glucosamine, a natural glucose derivative and an essential component of
      glycoproteins and proteoglycans, has been safely used to relieve osteoarthritis
      in humans. Recent studies have shown that glucosamine also possesses
      immunosuppressive properties and is effective in prolonging graft survival in
      mice. Whether this reagent is effective in human multiple sclerosis (MS), an
      inflammatory demyelination in the CNS, is not known. We thus investigated the
      therapeutic effect of glucosamine on experimental autoimmune encephalomyelitis
      (EAE), an animal model of MS. We demonstrated that oral, i.p., or i.v.
      administration of glucosamine significantly suppressed acute EAE, with reduced
      CNS inflammation and demyelination. A significant, albeit not strong, blockade of
      Th1 response and an up-regulation of Th2 cytokines (IL-5 and IL-10) are observed
      in the splenocytes of glucosamine-treated mice. Glucosamine also regulates IL-5
      and IL-10 in vitro. As glucosamine is able to effectively suppress acute EAE, has
      low or absent toxicity, and has been safely used in humans orally, our study
      suggests a potential use for this drug alone or in combination with other disease
      modifying immunotherapies to enhance their efficacy and reduce their doses in MS
      and possibly other autoimmune disorders. Furthermore, because glucosamine
      functions not simply as an immunosuppressant, but as a mild immunomodulator,
      administration of glucosamine provides a novel immunoregulatory approach for
      autoimmune disorders.

PMID- 16301625
TI  - Identification of the immunodominant HY H2-D(k) epitope and evaluation of the
      role of direct and indirect antigen presentation in HY responses.
AB  - Minor histocompatibility Ags derive from self-proteins and provoke allograft
      rejection and graft-vs-host disease in MHC-matched donor-recipient combinations.
      In this study, we define the HYD(k) epitope of the HY minor histocompatibility Ag
      as the 8mer peptide RRLRKTLL derived from the Smcy gene. Using HY tetramers, the
      response to this peptide was found to be immunodominant among the four
      characterized MHC class I-restricted HY epitopes (HYD(k)Smcy (defined here),
      HYK(k)Smcy, HYD(b)Uty, and HYD(b)Smcy). Indirect presentation stimulated a robust
      primary HYD(k)Smcy response. Indirect presentation and priming of HY-specific
      CD8+ T cells is also operative in the presence of a full MHC mismatch. To
      determine whether the indirect route of Ag presentation is required for HY
      priming, female parent into F1 (H2bxk) female recipient bone marrow chimeras were
      immunized with male cells of the other parental haplotype, limiting presentation
      to the direct pathway. The dominant H2b HY response (HYD(b)Uty) was dependent on
      indirect presentation. However, the dominant H2k HY response (HYD(k)Smcy) could
      be stimulated efficiently by the direct pathway. In contrast, secondary expansion
      of both HYD(k)Smcy and HYD(b)Uty-specific CD8+ T cells was effective only when Ag
      was presented by the direct route. Transgenic overproduction of Smcy mRNA within
      the immunizing cells resulted in a corresponding increase in the HYD(k)Smcy,
      HYD(b)Smcy, and HYK(k)Smcy-specific CD8+ T cell responses when presented via the
      direct pathway but did not enhance indirect presentation demonstrating the
      independent regulation of MHC class I-peptide occupancy in the two Ag-processing
      pathways.

PMID- 16301626
TI  - A role for double-stranded RNA-activated protein kinase PKR in Mycobacterium
      induced cytokine expression.
AB  - Following infection of the host by Mycobacterium tuberculosis, induction of
      cytokines is a major defense mechanism to limit the pathogen invasion. Cytokines
      interact with each other to form an intertwined network of pathways. For example,
      IFN and TNF have been shown to interact through common pathways including IFN
      inducible, dsRNA-activated serine/threonine protein kinase (PKR) induction. As a
      signal transducer, it has been conventionally known to regulate the induction of
      cytokine expression in response to virus infection through NF-kappaB. In light of
      the critical role of TNF in immunity and its cytotoxic effects mediated by PKR,
      we examined the role of the kinase in the regulation of immune response against
      M. tuberculosis using the interaction of bacillus Calmette-Guerin (BCG) and
      primary human blood monocytes as a model. Our results showed that BCG stimulates
      the induction of cytokine expression in human primary blood monocytes including
      TNF-alpha, IL-6, and IL-10. With the suppression of PKR by using PKR-mutant gene
      or 2-aminopurine as PKR inhibitor, we showed that the BCG-induced cytokine
      expression in human monocytes is regulated by the phosphorylation and activation
      of PKR. We also demonstrated that downstream of PKR induction is the activation
      of MAPK and translocation of NF-kappaB into the nucleus. NF-kappaB in turn
      mediates the transcription of specific cytokine genes. Taken together, PKR plays
      a critical role in the regulation of immune responses to mycobacterial infection
      and may serve as an important molecule in the innate antimycobacterial defense.

PMID- 16301627
TI  - Primary human T lymphocytes engineered with a codon-optimized IL-15 gene resist
      cytokine withdrawal-induced apoptosis and persist long-term in the absence of
      exogenous cytokine.
AB  - IL-15 is a common gamma-chain cytokine that has been shown to be more active than
      IL-2 in several murine cancer immunotherapy models. Although T lymphocytes do not
      produce IL-15, murine lymphocytes carrying an IL-15 transgene demonstrated
      superior antitumor activity in the immunotherapy of B16 melanoma. Thus, we sought
      to investigate the biological impact of constitutive IL-15 expression by human
      lymphocytes. In this report we describe the generation of a retroviral vector
      encoding a codon-optimized IL-15 gene. Alternate codon usage significantly
      enhanced the translational efficiency of this tightly regulated gene in
      retroviral vector-transduced cells. Activated human CD4+ and CD8+ human
      lymphocytes expressed IL-15Ralpha and produced high levels of cytokine upon
      retroviral transduction with the IL-15 vector. IL-15-transduced lymphocytes
      remained viable for up to 180 days in the absence of exogenous cytokine. IL-15
      vector-transduced T cells showed continued proliferation after cytokine
      withdrawal and resistance to apoptosis while retaining specific Ag recognition.
      In the setting of adoptive cell transfer, IL-15-transduced lymphocytes may
      prolong lymphocyte survival in vivo and could potentially enhance antitumor
      activity.

PMID- 16301628
TI  - Analysis of anthrax and plague biowarfare vaccine interactions with human
      monocyte-derived dendritic cells.
AB  - The anti-biowarfare anthrax and plague vaccines require repeated dosing to
      achieve adequate protection. To test the hypothesis that this limited
      immunogenicity results from the nature of vaccine interactions with the host
      innate immune system, we investigated molecular and cellular interactions between
      vaccines, dendritic cells (DCs), and T cells and explored the potential for
      adjuvants (pertussis) to boost induction of host immunity. Human monocyte-derived
      DCs were matured in the presence of vaccines and analyzed for their ability to
      induce Th1/Th2 development from naive T cells, expression of cell surface
      maturation/costimulation molecules, and cytokine production. The vaccines showed
      different behavior patterns. Although the plague vaccine is equivalent to control
      maturation factors in maturation and stimulation of DCs and induces strong MLR
      and Th outgrowth, the anthrax vaccine is a poor inducer of DC maturation, as
      indicated by low levels of HLA-DR, CD86, and CD83 induction and minimal
      proinflammatory cytokine production. Interestingly, however, anthrax vaccine
      treated DCs stimulate Th1 and Th2 outgrowth and a limited MLR response. There was
      no sustained negative modulatory effects of the anthrax vaccine on DCs, and its
      limited stimulatory effects could be overridden by coculture with pertussis.
      These results were supported by analysis of anthrax vaccine recall responses in
      subjects vaccinated using pertussis as an adjuvant, who demonstrate anthrax
      specific effector T cell responses. These data show that the anthrax vaccine is a
      suboptimal DC stimulus that may in part explain the observation that it requires
      repeated administration in vivo and offer a rational basis for the use of
      complementary DC-maturing adjuvants in combined immunotherapy.

PMID- 16301629
TI  - Apoptosis of antigen-specific T lymphocytes upon the engagement of CD8 by soluble
      HLA class I molecules is Fas ligand/Fas mediated: evidence for the involvement of
      p56lck, calcium calmodulin kinase II, and Calcium-independent protein kinase C
      signaling pathways and for NF-kappaB and NF-AT nuclear translocation.
AB  - The binding of soluble HLA class I (sHLA-I) molecules to CD8 on EBV-specific CTL
      induced up-regulation of Fas ligand (FasL) mRNA and consequent sFasL protein
      secretion. This, in turn, triggered CTL apoptosis by FasL/Fas interaction.
      Molecular analysis of the biochemical pathways responsible for FasL up-regulation
      showed that sHLA-I/CD8 interaction firstly induced the recruitment of src-like
      p56(lck) and syk-like Zap-70 protein tyrosine kinases (PTK). Interestingly,
      p59(fyn) was activated upon the engagement of CD3/TCR complex but not upon the
      interaction of sHLA-I with CD8. In addition, sHLA-I/CD8 interaction, which is
      different from signaling through the CD3/TCR complex, did not induce nuclear
      translocation of AP-1 protein complex. These findings suggest that CD8- and
      CD3/TCR-mediated activating stimuli can recruit different PTK and transcription
      factors. Indeed, the engagement of CD8 by sHLA-I led to the activation of Ca2+
      calmodulin kinase II pathway, which eventually was responsible for the NF-AT
      nuclear translocation. In addition, we found that the ligation of sHLA-I to CD8
      recruited protein kinase C, leading to NF-kappaB activation. Both NF-AT and NF
      kappaB were responsible for the induction of FasL mRNA and consequent CTL
      apoptosis. Moreover, FasL up-regulation and CTL apoptotic death were down
      regulated by pharmacological specific inhibitors of Ca2+/calmodulin/calcineurin
      and Ca2+-independent protein kinase C signaling pathways. These findings clarify
      the intracellular signaling pathways triggering FasL up-regulation and apoptosis
      in CTL upon sHLA-I/CD8 ligation and suggest that sHLA-I molecules can be proposed
      as therapeutic tools to modulate immune responses.

PMID- 16301630
TI  - The inhibition of autoreactive T cell functions by a peptide based on the CDR1 of
      an anti-DNA autoantibody is via TGF-beta-mediated suppression of LFA-1 and CD44
      expression and function.
AB  - Systemic lupus erythematosus (SLE), which is characterized by the increased
      production of autoantibodies and defective T cell responses, can be induced in
      mice by immunization with a human anti-DNA mAb that expresses a major Id,
      designated 16/6Id. A peptide based on the sequence of the CDR1 of the 16/6Id
      (human CDR1 (hCDR1)) ameliorated the clinical manifestations of SLE and down
      regulated, ex vivo, the 16/6Id-induced T cell proliferation. In this study, we
      examined the mechanism responsible for the hCDR1-induced modulation of T cell
      functions related to the pathogenesis of SLE. We found that injection of hCDR1
      into BALB/c mice concomitant with their immunization with 16/6Id resulted in a
      marked elevation of TGF-beta secretion 10 days later. Addition of TGF-beta
      suppressed the 16/6Id-stimulated T cell proliferation similarly to hCDR1. In
      addition, we provide evidence that one possible mechanism underlying the hCDR1-
      and TGFbeta-induced inhibition of T cell proliferation is by down-regulating the
      expression, and therefore the functions, of a pair of key cell adhesion
      receptors, LFA-1 (alphaLbeta2) and CD44, which operate as accessory molecules in
      mediating APC-T cell interactions. Indeed, T cells of mice treated with hCDR1
      showed a TGF-beta-induced suppression of adhesion to the LFA-1 and CD44 ligands,
      hyaluronic acid and ICAM-1, respectively, induced by stromal cell-derived factor
      1alpha and PMA. The latter suppression is through the inhibition of ERK
      phosphorylation. Thus, the down-regulation of SLE-associated responses by hCDR1
      treatment may be due to the effect of the up-regulated TGF-beta on the expression
      and function of T cell adhesion receptors and, consequently, on T cell
      stimulation, adhesion, and proliferation.

PMID- 16301631
TI  - Anti-CD25 antibody enhancement of vaccine-induced immunogenicity: increased
      durable cellular immunity with reduced immunodominance.
AB  - An efficacious vaccine strategy must be capable of inducing strong responses of
      an appropriate phenotype that are long lasting and sufficiently broad to prevent
      pathogen escape mechanisms. In the present study, we use anti-CD25 mAb to augment
      vaccine-induced immunity in mice. We demonstrate that coformulation of Ab and
      poxviral- or adenoviral-vectored vaccines induces significantly increased T cell
      responses to a malaria Ag; prior anti-CD25 Ab administration was not required for
      this effect. Furthermore, this vaccination approach subverts immunodominant
      epitope hierarchies by enhancing responses to subdominant epitopes induced by
      recombinant modified vaccinia virus Ankara immunization. Administration of anti
      CD25 with a vaccine also induces more durable immunity compared with vaccine
      alone; significantly higher T cell responses were observed 100 days after the
      primary immunization. Enhanced immunogenicity is observed for multiple vaccine
      types with enhanced CD4+ and CD8+ T cell responses induced by bacillus Calmette
      Guerin and a recombinant subunit protein vaccine to hepatitis B virus and with
      multiple Ags of tumor, viral, bacterial, and parasitic origin. Vaccine strategies
      incorporating anti-CD25 lead to improved protection against pre-erythrocytic
      malaria challenge. These data underpin new strategies for the design and
      development of more efficacious vaccines in clinical settings.

PMID- 16301632
TI  - Early kinetic window of target T cell susceptibility to CD25+ regulatory T cell
      activity.
AB  - Peripheral tolerance is maintained in part by thymically derived CD25+CD4+ T
      cells (regulatory T cells (Tregs)). Their mechanism of action has not been well
      characterized. Therefore, to get a better understanding of Treg action, we
      investigated the kinetics of murine Treg activity in vitro. Tregs were
      suppressive within a surprisingly narrow kinetic window: necessary and sufficient
      only in the first 6-10 h of culture. Visualization of this time frame, using a
      sensitive single-cell assay for IL-2, revealed the early elaboration of target
      cell IL-2 producers in the first 6 h despite the presence of CD25+CD4+ Tregs.
      However, after 6 h, a rapid rise in the number of IL-2 producers in the absence
      of Tregs was dramatically abrogated by the presence of Tregs. Importantly, the
      timing of suppression was dictated by the kinetics of target T cell activation
      suggesting that early target T cell signals may alter susceptibility to
      suppression. Modulating target T cell activation signals with provision of CD28,
      IL-2, or high Ag dose all abrogated suppression of proliferation late in culture.
      However, only CD28 signals enabled target T cells to resist the early Treg
      induced down-regulation of IL-2. Therefore the quality of early target T cell
      activation signals, in particular engagement of CD28, represents an important
      control point in the balance between vulnerability and resistance to Treg
      suppression.

PMID- 16301633
TI  - Plasmacytoid dendritic cells of different origins have distinct characteristics
      and function: studies of lymphoid progenitors versus myeloid progenitors.
AB  - Plasmacytoid dendritic cells (pDCs) play a central role in host innate and
      adaptive immunity and are thought to be of lymphoid origin. However, in IL
      7Ralpha-/- mice, which are deficient in T and B lymphocytes, pDCs are still found
      in lymphoid organs, which suggests that there is a lymphoid-independent pathway
      for the development of pDCs. Previous work has demonstrated that pDCs originate
      from both lymphoid and myeloid progenitors (MPs). However, it is not clear
      whether the function of pDCs is different relative to their origin. In an effort
      to compare the characteristics and functions between pDCs generated from
      different progenitors, we performed adoptive transfer studies using highly
      enriched populations of common lymphoid progenitors (CLPs) and MPs from the bone
      marrow of control mice and examined their potential and developmental kinetics
      for the generation of pDCs. Interestingly, although CLPs were polarized to
      generate pDCs, MPs were polarized to generate conventional dendritic cells and
      the kinetics of pDC generation from MPs was reached earlier than from CLPs.
      Furthermore, CLPs have the potential to generate more pDCs on a per cell basis.
      Moreover, MP-derived pDCs produce relatively higher levels of IFN-alpha than CLP
      derived pDCs following CpG stimulation. These data indicate that MPs are
      multipotential and have the capacity to develop into not only myeloid cells, but
      also pDCs, which have distinct characteristics and function compared to that of
      lymphoid origin and, therefore, imply a more important role for MP-derived pDCs
      in conditions where the function of lymphoid progenitors is impaired or
      compromised.

PMID- 16301634
TI  - Cooperation between 4-1BB and ICOS in the immune response to influenza virus
      revealed by studies of CD28/ICOS-deficient mice.
AB  - CD28, ICOS, and 4-1BB each play distinct roles in the CD8 T cell response to
      influenza virus. CD28-/- mice are severely impaired in primary CD8 T cell
      expansion and fail to mount a secondary response to influenza. Influenza-specific
      CD8 T cells expand normally in ICOS-/- mice, with only a small and transient
      defect late in the primary response and an unimpaired secondary response.
      Conversely, 4-1BB/4-1BBL interaction is dispensable for the primary CD8 T cell
      response to influenza, but maintains CD8 T cell survival and controls the size of
      the secondary response. Previous results showed that a single dose of agonistic
      anti-4-1BB Ab at priming allowed partial restoration of primary CD8 T cell
      expansion and full recovery of the secondary CD8 T cell responses to influenza in
      CD28-/- mice. In this study we show that anti-4-1BB fails to correct the CD8 T
      cell defect in CD28-/-ICOS-/- mice, suggesting that ICOS partially compensates
      for CD28 in this model. In support of this hypothesis, we found that anti-4-1BB
      enhances ICOS expression on both T cell subsets and that anti-4-1BB and anti-ICOS
      can synergistically activate CD4 and CD8 T cells. Furthermore, ICOS and 4-1BB can
      cooperate to directly stimulate isolated CD28-/- CD8 T cells. These results
      reveal a novel interaction between the ICOS and 4-1BB costimulatory pathways as
      well as unexpected redundancy between CD28 and ICOS in primary CD8 T cell
      expansion. These findings have implications for costimulation of human T cell
      responses in diseases such as AIDS or rheumatoid arthritis, in which CD28- T
      cells accumulate.

PMID- 16301635
TI  - A novel mucosal vaccine based on live Lactococci expressing E7 antigen and IL-12
      induces systemic and mucosal immune responses and protects mice against human
      papillomavirus type 16-induced tumors.
AB  - Current strategies to prevent or treat human papillomavirus type 16 (HPV-16)
      infection are promising, but remain costly. More economical but efficient
      vaccines are thus needed. In this study, we evaluated the protective effects of
      mucosally coadministered live Lactococcus lactis strains expressing cell wall
      anchored E7 Ag and a secreted form of IL-12 to treat HPV-16-induced tumors in a
      murine model. When challenged with lethal levels of tumor cell line TC-1
      expressing E7, immunized mice showed full prevention of TC-1-induced tumors, even
      after a second challenge, suggesting that this prophylactic immunization can
      provide long-lasting immunity. Therapeutic immunization with L. lactis
      recombinant strains, i.e., 7 days after TC-1 injection, induced regression of
      palpable tumors in treated mice. The antitumor effects of vaccination occurred
      through a CTL response, which is CD4+ and CD8+ dependent. Furthermore, immunized
      mice developed an E7-specific mucosal immune response. These preclinical results
      suggest the feasibility of the low-cost mucosal vaccination and/or immunotherapy
      strategies against HPV-related cervical cancer in humans.

PMID- 16301636
TI  - Targeted expression of human CD1d in transgenic mice reveals independent roles
      for thymocytes and thymic APCs in positive and negative selection of Valpha14i
      NKT cells.
AB  - CD1d-dependent invariant Valpha14 (Valpha14i) NKT cells are innate T lymphocytes
      expressing a conserved semi-invariant TCR, consisting, in mice, of the invariant
      Valpha14-Jalpha18 TCR alpha-chain paired mostly with Vbeta8.2 and Vbeta7. The
      cellular requirements for thymic positive and negative selection of Valpha14i NKT
      cells are only partially understood. Therefore, we generated transgenic mice
      expressing human CD1d (hCD1d) either on thymocytes, mainly CD4+ CD8+ double
      positive, or on APCs, the cells implicated in the selection of Valpha14i NKT
      cells. In the absence of the endogenous mouse CD1d (mCD1d), the expression of
      hCD1d on thymocytes, but not on APCs, was sufficient to select Valpha14i NKT
      cells that proved functional when activated ex vivo with the Ag alpha-galactosyl
      ceramide. Valpha14i NKT cells selected by hCD1d on thymocytes, however, attained
      lower numbers than in control mice and expressed essentially Vbeta8.2. The low
      number of Vbeta8.2+ Valpha14i NKT cells selected by hCD1d on thymocytes was not
      reversed by the concomitant expression of mCD1d, which, instead, restored the
      development of Vbeta7+ Valpha14i NKT cells. Vbeta8.2+, but not Vbeta7+, NKT cell
      development was impaired in mice expressing both hCD1d on APCs and mCD1d. Taken
      together, our data reveal that selective CD1d expression by thymocytes is
      sufficient for positive selection of functional Valpha14i NKT cells and that both
      thymocytes and APCs may independently mediate negative selection.

PMID- 16301637
TI  - The neuropeptide vasoactive intestinal peptide generates tolerogenic dendritic
      cells.
AB  - Tolerogenic dendritic cells (DCs) play an important role in maintaining
      peripheral tolerance through the induction/activation of regulatory T cells
      (Treg). Endogenous factors contribute to the functional development of
      tolerogenic DCs. In this report, we present evidence that two known
      immunosuppressive neuropeptides, the vasoactive intestinal peptide (VIP) and the
      pituitary adenylate cyclase-activating polypeptide (PACAP), contribute to the
      development of bone marrow-derived tolerogenic DCs in vitro and in vivo. The
      VIP/PACAP-generated DCs are CD11c(low)CD45RB(high), do not up-regulate CD80,
      CD86, and CD40 following LPS stimulation, and secrete high amounts of IL-10. The
      induction of tolerogenic DCs is mediated through the VPAC1 receptor and protein
      kinase A, and correlates with the inhibition of IkappaB phosphorylation and of NF
      kappaBp65 nuclear translocation. The VIP/PACAP-generated DCs induce functional
      Treg in vitro and in vivo. The VIP/DC-induced Treg resemble the previously
      described Tr1 in terms of phenotype and cytokine profile, suppress primarily Th1
      responses including delayed-type hypersensitivity, and transfer suppression to
      naive hosts. The effect of VIP/PACAP on the DC-Treg axis represents an additional
      mechanism for their general anti-inflammatory role, particularly in anatomical
      sites which exhibit immune deviation or privilege.

PMID- 16301638
TI  - Murine and human IL-7 activate STAT5 and induce proliferation of normal human pro
      B cells.
AB  - The role of IL-7 in lymphoid development and T cell homeostasis has been
      extensively documented. However, the role of IL-7 in human B cell development
      remains unclear. We used a xenogeneic human cord blood stem cell/murine stromal
      cell culture to study the development of CD19+ B-lineage cells expressing the IL
      7R. CD34+ cord blood stem cells were cultured on the MS-5 murine stromal cell
      line supplemented with human G-CSF and stem cell factor. Following an initial
      expansion of myeloid/monocytoid cells within the initial 2 wk, CD19+/pre-BCR- pro
      B cells emerged, of which 25-50% expressed the IL-7R. FACS-purified CD19+/IL-7R+
      cells were larger and, when replated on MS-5, underwent a dose-dependent
      proliferative response to exogenous human IL-7 (0.01-10.0 ng/ml). Furthermore,
      STAT5 phosphorylation was induced by the same concentrations of human IL-7.
      CD19+/IL-7R- cells were smaller and did not proliferate on MS-5 after stimulation
      with IL-7. In a search for cytokines that promote human B cell development in the
      cord blood stem cell/MS-5 culture, we made the unexpected finding that murine IL
      7 plays a role. Murine IL-7 was detected in MS-5 supernatants by ELISA,
      recombinant murine IL-7 induced STAT5 phosphorylation in CD19+/IL-7R+ pro-B cells
      and human B-lineage acute lymphoblastic leukemias, and neutralizing anti-murine
      IL-7 inhibited development of CD19+ cells in the cord blood stem cell/MS-5
      culture. Our results support a model wherein IL-7 transduces a replicative signal
      to normal human B-lineage cells that is complemented by additional stromal cell
      derived signals essential for normal human B cell development.

PMID- 16301639
TI  - Bone marrow-derived dendritic cells reverse the anergic state of CD4+CD25+ T
      cells without reversing their suppressive function.
AB  - Dendritic cells (DC) are potent inducers of immunity to foreign Ags, but also
      contribute to self-tolerance by induction of regulatory T cells or
      deletion/anergy of self-reactive T cells. In this study, we have studied the
      capacity of DC to activate naturally occurring CD4+CD25+ regulatory T cells as
      well as the ability of CD4+CD25+ T cells to suppress the DC-mediated activation
      of CD4+CD25- T cells. Mature bone marrow-derived dendritic cells, but not splenic
      DC, were able to induce the proliferation of CD4+CD25+ T cells in the presence of
      a polyclonal stimulus and in the absence of exogenous IL-2. The DC-induced
      proliferative response of the CD4+CD25+ T cells was partially dependent on IL-2
      produced by a small number of contaminating CD25+ effector cells. Because bone
      marrow-derived dendritic cells induce proliferation of both CD4+CD25+ and
      CD4+CD25- T cells in vitro, it was impossible to assay the suppressive function
      of the CD4+CD25+ T cells using [3H]TdR uptake or CFSE dilution. We therefore
      measured IL-2 production in cocultures of CD4+CD25+ and CD4+CD25- T cells using
      the IL-2 secretion assay. Surprisingly, CD4+CD25+ T cells markedly suppressed IL
      2 secretion by the CD4+CD25- T cells without inhibiting their proliferation.
      Collectively, these results suggest that Ag presentation by DC can induce the
      expansion of CD4+CD25+ T cells while simultaneously activating their ability to
      suppress cytokine secretion by effector T cells.

PMID- 16301640
TI  - The ICOS molecule plays a crucial role in the development of mucosal tolerance.
AB  - The ICOS molecule stimulates production of the immunoregulatory cytokine IL-10,
      suggesting an important role for ICOS in controlling IL-10-producing regulatory T
      cells and peripheral T cell tolerance. In this study we investigate whether ICOS
      is required for development of oral, nasal, and high dose i.v. tolerance. Oral
      administration of encephalitogenic myelin oligodendrocyte glycoprotein (MOG) 35
      55 peptide to ICOS-deficient (ICOS-/-) mice did not inhibit experimental
      autoimmune encephalomyelitis (EAE), T cell proliferation, or IFN-gamma
      production, in striking contrast to wild-type mice. Similarly, intranasal
      administration of MOG(35-55) before EAE induction suppressed EAE and T cell
      responses in wild-type, but not in ICOS-/-, mice. In contrast, ICOS-/- mice were
      as susceptible as wild-type mice to high dose tolerance. These results indicate
      that ICOS plays an essential and specific role in mucosal tolerance and that
      distinct costimulatory pathways differentially regulate different forms of
      peripheral tolerance. Surprisingly, CD4+ cells from MOG-fed wild-type and ICOS-/-
      mice could transfer suppression to wild-type recipients, indicating that
      functional regulatory CD4+ cells can develop in the absence of ICOS. However,
      CD4+ T cells from MOG-fed wild-type mice could not transfer suppression to ICOS-/
      recipients, suggesting that ICOS may have a key role in controlling the effector
      functions of regulatory T cells. These results suggest that stimulating ICOS may
      provide an effective therapeutic approach for promoting mucosal tolerance.

PMID- 16301641
TI  - Effects of aryl hydrocarbon receptor signaling on the modulation of TH1/TH2
      balance.
AB  - An orally active antiallergic agent, M50367, skews the Th1/Th2 balance toward Th1
      dominance by suppressing naive Th cell differentiation into Th2 cells in vitro.
      Administration results in the suppression of IgE synthesis and peritoneal
      eosinophilia in vivo. In this report, we determined that M50354 (an active
      metabolite of M50367) was a ligand for the aryl hydrocarbon receptor (AhR); the
      immunological effects of this compound on in vitro Th1/Th2 differentiation from
      naive Th cells and Th1/Th2 balance in vivo were manifested through binding to
      AhR. These effects were completely abolished in AhR-deficient mice. AhR
      expression in the naive Th cell was significantly up-regulated by costimulation
      of TCR and CD28. Suppression of naive Th cell differentiation into Th2 cells via
      binding of M50354 to AhR was associated with inhibition of GATA-3 expression in
      Th cells. In addition, forced expression of a constitutively active form of AhR
      or activation of AhR by the addition of representative ligands suppressed naive
      Th cell differentiation into Th2 cells. Based on these results, we conclude that
      AhR functions as a modulator of the in vivo Th1/Th2 balance through activation in
      naive Th cells.

PMID- 16301642
TI  - Human white blood cells synthesize morphine: CYP2D6 modulation.
AB  - Human plasma contains low, but physiologically significant, concentrations of
      morphine that can increase following trauma or exercise. We now demonstrate that
      normal, human white blood cells (WBC), specifically polymorphonuclear cells,
      contain and have the ability to synthesize morphine. We also show that WBC
      express CYP2D6, an enzyme capable of synthesizing morphine from tyramine,
      norlaudanosoline, and codeine. Significantly, we also show that morphine can be
      synthesized by another pathway via l-3,4-dihydroxyphenylalanine (L-DOPA).
      Finally, we show that WBC release morphine into their environment. These studies
      provide evidence that 1) the synthesis of morphine by various animal tissues is
      more widespread than previously thought and now includes human immune cells. 2)
      Moreover, another pathway for morphine synthesis exists, via L-DOPA,
      demonstrating an intersection between dopamine and morphine pathways. 3) WBC can
      release morphine into the environment to regulate themselves and other cells,
      suggesting involvement in autocrine signaling since these cells express the mu3
      opiate receptor subtype.

PMID- 16301643
TI  - Aberrant IgM signaling promotes survival of transitional T1 B cells and prevents
      tolerance induction in lupus-prone New Zealand black mice.
AB  - New Zealand Black (NZB) mice develop a lupus-like syndrome. Although the precise
      immune defects leading to autoantibody production in these mice have not been
      characterized, they possess a number of immunologic abnormalities suggesting that
      B cell tolerance may be defective. In the bone marrow, immature self-reactive B
      cells that have failed to edit their receptors undergo apoptosis as a consequence
      of Ig receptor engagement. Splenic transitional T1 B cells are recent bone marrow
      emigrants that retain these signaling properties, ensuring that B cells
      recognizing self-Ags expressed only in the periphery are deleted from the naive B
      cell repertoire. In this study we report that this mechanism of tolerance is
      defective in NZB mice. We show that NZB T1 B cells are resistant to apoptosis
      after IgM cross-linking in vitro. Although extensive IgM cross-linking usually
      leads to deletion of T1 B cells, in NZB T1 B cells we found that it prevents
      mitochondrial membrane damage, inhibits activation of caspase-3, and promotes
      cell survival. Increased survival of NZB T1 B cells was associated with aberrant
      up-regulation of Bcl-2 after Ig receptor engagement. We also show that there is a
      markedly increased proportion of NZB T1 B cells that express elevated levels of
      Bcl-2 in vivo and provide evidence that up-regulation of Bcl-2 follows encounter
      with self-Ag in vivo. Thus, we propose that aberrant cell signaling in NZB T1 B
      cells leads to the survival of autoreactive B cells, which predisposes NZB mice
      to the development of autoimmunity.

PMID- 16301644
TI  - Programmed death-1 (PD-1):PD-ligand 1 interactions inhibit TCR-mediated positive
      selection of thymocytes.
AB  - Positive selection during thymocyte development is driven by the affinity and
      avidity of the TCR for MHC-peptide complexes expressed in the thymus. In this
      study, we show that programmed death-1 (PD-1), a member of the B7/CD28 family of
      costimulatory receptors, inhibits TCR-mediated positive selection through PD-1
      ligand 1 (PD-L1):PD-1 interactions. Transgenic mice that constitutively
      overexpress PD-1 on CD4+CD8+ thymocytes display defects in positive selection in
      vivo. Using an in vitro model system, we find that PD-1 is up-regulated following
      TCR engagement on CD4+CD8+ murine thymocytes. Coligation of TCR and PD-1 on
      CD4+CD8+ thymocytes with a novel PD-1 agonistic mAb inhibits the activation of
      ERK and up-regulation of bcl-2, both of which are downstream mediators essential
      for positive selection. Inhibitory signals through PD-1 can overcome the ability
      of positive costimulators, such as CD2 and CD28, to facilitate positive
      selection. Finally, defects in positive selection that result from PD-1
      overexpression in thymocytes resolve upon elimination of PD-L1, but not PD-1
      ligand 2, expression. PD-L1-deficient mice have increased numbers of CD4+CD8+ and
      CD4+ thymocytes, indicating that PD-L1 is involved in normal thymic selection.
      These data demonstrate that PD-1:PD-L1 interactions are critical to positive
      selection and play a role in shaping the T cell repertoire.

PMID- 16301645
TI  - Respiratory tolerance is inhibited by the administration of corticosteroids.
AB  - Corticosteroids constitute the most effective current anti-inflammatory therapy
      for acute and chronic forms of allergic diseases and asthma. Corticosteroids are
      highly effective in inhibiting the effector function of Th2 cells, eosinophils,
      and epithelial cells. However, treatment with corticosteroids may also limit
      beneficial T cell responses, including respiratory tolerance and the development
      of regulatory T cells (T(Reg)), which actively suppress inflammation in allergic
      diseases. To examine this possibility, we investigated the effects of
      corticosteroid administration on the development of respiratory tolerance.
      Respiratory exposure to Ag-induced T cell tolerance and prevented the subsequent
      development of allergen-induced airway hyperreactivity. However, treatment with
      dexamethasone during the delivery of respiratory Ag prevented tolerance, such
      that allergen sensitization and severe airway hyperreactivity subsequently
      occurred. Treatment with dexamethasone during respiratory exposure to allergen
      eliminated the development of IL-10-secreting dendritic cells, which was required
      for the induction of IL-10-producing allergen-specific T(Reg) cells. Therefore,
      because allergen-specific T(Reg) cells normally develop to prevent allergic
      disease and asthma, our results suggest that treatment with corticosteroids,
      which limit the development of T(Reg) cells and tolerance to allergens, could
      enhance subsequent Th2 responses and aggravate the long-term course of allergic
      diseases and asthma.

PMID- 16301646
TI  - CD8 T cell sensory adaptation dependent on TCR avidity for self-antigens.
AB  - Adaptation of the T cell activation threshold may be one mechanism to control
      autoreactivity. To investigate its occurrence in vivo, we engineered a transgenic
      mouse model with increased TCR-dependent excitability by expressing a Zap70 gain
      of-function mutant (ZAP-YEEI) in postselection CD8 thymocytes and T cells.
      Increased basal phosphorylation of the Zap70 substrate linker for activation of T
      cells was detected in ZAP-YEEI-bearing CD8 T cells. However, these cells were not
      activated, but had reduced levels of TCR and CD5. Moreover, they produced lower
      cytokine amounts and showed faster dephosphorylation of linker for activation of
      T cells and ERK upon activation. Normal TCR levels and cytokine production were
      restored by culturing cells in the absence of TCR/spMHC interaction,
      demonstrating dynamic tuning of peripheral T cell responses. The effect of
      avidity for self-ligand(s) on this sensory adaptation was studied by expressing
      ZAP-YEEI in P14 or HY TCR transgenic backgrounds. Unexpectedly, double-transgenic
      animals expressed ZAP-YEEI prematurely in double-positive thymocytes, but no
      overt alteration of selection processes was observed. Instead, modifications of
      TCR and CD5 expression due to ZAP-YEEI suggested that signal tuning occurred
      during thymic maturation. Importantly, although P14 x ZAP-YEEI peripheral CD8 T
      cells were reduced in number and showed lower Ag-induced cytokine production and
      limited lymphopenia-driven proliferation, the peripheral survival/expansion and
      Ag responsiveness of HY x ZAP-YEEI cells were enhanced. Our data provide support
      for central and peripheral sensory T cell adaptation induced as a function of TCR
      avidity for self-ligands and signaling level. This may contribute to buffer
      excessive autoreactivity while optimizing TCR repertoire usage.

PMID- 16301647
TI  - Short-interfering RNA-mediated Lck knockdown results in augmented downstream T
      cell responses.
AB  - The Src family kinase Lck is essential for T cell Ag receptor-mediated signaling.
      In this study, we report the effects of acute elimination of Lck in Jurkat TAg
      and primary T cells using RNA interference mediated by short-interfering RNAs. In
      cells with Lck knockdown (kd), proximal TCR signaling was strongly suppressed as
      indicated by reduced zeta-chain phosphorylation and intracellular calcium
      mobilization. However, we observed sustained and elevated phosphorylation of
      ERK1/2 in Lck kd cells 30 min to 2 h after stimulation. Downstream effects on
      immune function as determined by activation of a NFAT-AP-1 reporter, and TCR/CD28
      stimulated IL-2 secretion were strongly augmented in Jurkat and primary T cells,
      respectively. As expected, overexpression of SHP-1 in Jurkat cells inhibited TCR
      induced NFAT-AP-1 activation, but this effect could be overcome by simultaneous
      kd of Lck. Furthermore, acute elimination of Lck also suppressed TCR-mediated
      activation of SHP-1, suggesting the possible role of SHP-1 in a negative feedback
      loop originating from Lck. This report underscores Lck as an important mediator
      of proximal TCR signaling, but also indicates a suppressive role on downstream
      immune function.

PMID- 16301648
TI  - A distal regulatory region is required for constitutive and IFN-beta-induced
      expression of murine TLR9 gene.
AB  - TLR9 is critical for the recognition of unmethylated CpG DNA in innate immunity.
      Accumulating evidence suggests distinct patterns of TLR9 expression in various
      types of cells. However, the molecular mechanism of TLR9 expression has received
      little attention. In the present study, we demonstrate that transcription of
      murine TLR9 is induced by IFN-beta in peritoneal macrophages and a murine
      macrophage cell line RAW264.7. TLR9 is regulated through two cis-acting regions,
      a distal regulatory region (DRR) and a proximal promoter region (PPR), which are
      separated by approximately 2.3 kbp of DNA. Two IFN-stimulated response
      element/IFN regulatory factor-element (ISRE/IRF-E) sites, ISRE/IRF-E1 and
      ISRE/IRF-E2, at the DRR and one AP-1 site at the PPR are required for
      constitutive expression of TLR9, while only the ISRE/IRF-E1 motif is essential
      for IFN-beta induction. In vivo genomic footprint assays revealed constitutive
      factor occupancy at the DRR and the PPR and an IFN-beta-induced occupancy only at
      the DRR. IRF-2 constitutively binds to the two ISRE/IRF-E sites at the DRR, while
      IRF-1 and STAT1 are induced to bind to the two ISRE/IRF-E sites and the ISRE/IRF
      E1, respectively, only after IFN-beta treatment. AP-1 subunits, c-Jun and c-Fos,
      were responsible for the constitutive occupancy at the proximal region. Induction
      of TLR9 by IFN-beta was absent in STAT1-/- macrophages, while the level of TLR9
      induction was decreased in IRF-1-/- cells. This study illustrates the crucial
      roles for AP-1, IRF-1, IRF-2, and STAT1 in the regulation of murine TLR9
      expression.

PMID- 16301649
TI  - Stat1-dependent synergistic activation of T-bet for IgG2a production during early
      stage of B cell activation.
AB  - During the adaptive phase of an immune response, naive B cells receive multiple
      signals to become activated. Among them are the engagement of the B cell Ag
      receptor and stimulation by cytokines. Specifically for an anti-microbial
      response, the recognition of viral or bacterial Ags by the BCR and the
      stimulation of IFN-gamma result in the predominant production of IgG2a. The T-bet
      protein has been shown to be required for class switching to IgG2a. In this
      report we further investigated the regulation of T-bet gene expression during the
      early stage of B cell activation. We show that there is a striking synergistic
      activation of T-bet in primary B cells when both the BCR and IFN-gamma signaling
      pathways are activated. The synergistic activation of T-bet correlates with a
      100% increase in the number of B cells that produce IgG2a. This transcription
      synergy on T-bet is transient in the first 24 h of B cell activation.
      Furthermore, we demonstrate that the synergistic activation of T-bet is dependent
      on Stat1 and that Stat1 is required for the IgG2a germline transcription and the
      production of IgG2a in response to the simultaneous signaling of BCR and IFN
      gamma. Finally, we show that Stat1 directly regulates the expression of T-bet by
      binding to the T-bet promoter. These results reveal the mechanism of regulation
      of T-bet expression and uncover a novel physiological function of Stat1 for B
      cell activation.

PMID- 16301650
TI  - Developmental changes in the human heavy chain CDR3.
AB  - The CDR3 of the Ig H chain (CDR3(H)) is significantly different in fetal and
      adult repertoires. To understand the mechanisms involved in the developmental
      changes in the CDR3(H) of Ig H chains, sets of nonproductive V(H)DJ(H)
      rearrangements obtained from fetal, full-term neonates and adult single B cells
      were analyzed and compared with the corresponding productive repertoires.
      Analysis of the nonproductive repertoires was particularly informative in
      assessing developmental changes in the molecular mechanisms of V(H)DJ(H)
      recombination because these rearrangements did not encode a protein and therefore
      their distribution was not affected by selection. Although a number of
      differences were noted, the major reasons that fetal B cells expressed Ig H
      chains with shorter CDR3(H) were both diminished TdT activity in the DJ(H)
      junction and the preferential use of the short J(H) proximal D segment D7-27. The
      enhanced usage of D7-27 by fetal B cells appeared to relate to its position in
      the locus rather than its short length. The CDR3(H) progressively acquired a more
      adult phenotype during ontogeny. In fetal B cells, there was decreased recurrent
      DJ(H) rearrangements before V(H)-DJ(H) rearrangement and increased usage of
      junctional microhomologies both of which also converted to the adult pattern
      during ontogeny. Overall, these results indicate that the decreased length and
      complexity of the CDR3(H) of fetal B cells primarily reflect limited enzymatic
      modifications of the joins as well as a tendency to use proximal D and J(H)
      segments during DJ(H) rearrangements.

PMID- 16301651
TI  - Distal enhancer elements transcribe intergenic RNA in the IL-10 family gene
      cluster.
AB  - The IL-10 gene and homologs IL-19, IL-20, and IL-24 are expressed within a highly
      conserved 145-kb cytokine gene cluster. Like the Th2 IL-4 cytokine gene cluster,
      it is feasible that there is coordinate regulation of these cytokines by distal
      regulatory elements spanning the locus. We initiated a search to characterize
      regulatory elements within the IL-10 family locus and present data herein on a
      conserved 40-kb region between the IL-19 and IL-10 genes. We map the location of
      17 DNase I-hypersensitive sites in different murine T cell populations and
      identify three enhancer elements, which function in T cells in vitro. Two of
      these enhancer elements, located 9 kb upstream and 6.45 kb downstream of IL-10,
      display cell-specific function in the Th1-Th2 cell clones AE7 and D10 and also
      exhibit basic promoter activity. The downstream element, IL-10CNS+6.45, binds AP
      1 in the absence of NFAT and expresses intergenic RNA in a Th2-specific manner,
      further validating its role as a Th2-specific enhancer/promoter element. We show
      that the five most highly conserved noncoding sequences in the 40-kb region
      transcribe intergenic RNA; four of these regions possess promoter activity in
      vitro that could account for the expression of these transcripts. Hence, we
      speculate that these novel regulatory elements in the IL-10 family gene locus
      function via an intermediate regulatory RNA.

PMID- 16301652
TI  - Multiple TLRs are expressed in human cholangiocytes and mediate host epithelial
      defense responses to Cryptosporidium parvum via activation of NF-kappaB.
AB  - Infection of epithelial cells by Cryptosporidium parvum triggers a variety of
      host-cell innate and adaptive immune responses including release of
      cytokines/chemokines and up-regulation of antimicrobial peptides. The mechanisms
      that trigger these host-cell responses are unclear. Thus, we evaluated the role
      of TLRs in host-cell responses during C. parvum infection of cultured human
      biliary epithelia (i.e., cholangiocytes). We found that normal human
      cholangiocytes express all known TLRs. C. parvum infection of cultured
      cholangiocytes induces the selective recruitment of TLR2 and TLR4 to the
      infection sites. Activation of several downstream effectors of TLRs including IL
      1R-associated kinase, p-38, and NF-kappaB was detected in infected cells.
      Transfection of cholangiocytes with dominant-negative mutants of TLR2 and TLR4,
      as well as the adaptor molecule myeloid differentiation protein 88 (MyD88),
      inhibited C. parvum-induced activation of IL-1R-associated kinase, p-38, and NF
      kappaB. Short-interfering RNA to TLR2, TLR4, and MyD88 also blocked C. parvum
      induced NF-kappaB activation. Moreover, C. parvum selectively up-regulated human
      beta-defensin-2 in directly infected cells, and inhibition of TLR2 and TLR4
      signals or NF-kappaB activation were each associated with a reduction of C.
      parvum-induced human beta-defensin-2 expression. A significantly higher number of
      parasites were detected in cells transfected with a MyD88 dominant-negative
      mutant than in the control cells at 48-96 h after initial exposure to parasites,
      suggesting MyD88-deficient cells were more susceptible to infection. These
      findings demonstrate that cholangiocytes express a variety of TLRs, and suggest
      that TLR2 and TLR4 mediate cholangiocyte defense responses to C. parvum via
      activation of NF-kappaB.

PMID- 16301653
TI  - Human cytomegalovirus encodes an MHC class I-like molecule (UL142) that functions
      to inhibit NK cell lysis.
AB  - Clinical and low passage strains of human CMV (HCMV) encode an additional MHC
      class I-related molecule UL142, in addition to the previously described UL18. The
      UL142 open reading frame is encoded within the ULb' region which is missing from
      a number of common high passage laboratory strains. Cells expressing UL142
      following transfection, and fibroblasts infected with a recombinant adenovirus
      expressing UL142, were used to screen both polyclonal NK cells and NK cell
      clones, in a completely autologous system. Analysis of 100 NK cell clones derived
      from five donors, revealed 23 clones that were inhibited by fibroblasts
      expressing UL142 alone. Small-interfering RNA-mediated knockdown of UL142 mRNA
      expression in HCMV-infected cells resulted in increased sensitivity to lysis.
      From these data we conclude that UL142 is a novel HCMV-encoded MHC class I
      related molecule which inhibits NK cell killing in a clonally dependent manner.

PMID- 16301654
TI  - Heterogeneous human NK cell responses to Plasmodium falciparum-infected
      erythrocytes.
AB  - Human NK cells can respond rapidly to Plasmodium falciparum-infected RBC (iRBC)
      to produce IFN-gamma. In this study, we have examined the heterogeneity of this
      response among malaria-naive blood donors. Cells from all donors become partially
      activated (up-regulating CD69, perforin, and granzyme) upon exposure to iRBC but
      cells from only a subset of donors become fully activated (additionally up
      regulating CD25, IFN-gamma, and surface expression of lysosomal-associated
      membrane protein 1 (LAMP-1)). Although both CD56dim and CD56bright NK cell
      populations can express IFN-gamma in response to iRBC, CD25 and LAMP-1 are up
      regulated only by CD56dim NK cells and CD69 is up-regulated to a greater extent
      in this subset; by contrast, perforin and granzyme A are preferentially up
      regulated by CD56bright NK cells. NK cells expressing IFN-gamma in response to
      iRBC always coexpress CD69 and CD25 but rarely LAMP-1, suggesting that individual
      NK cells respond to iRBC either by IFN-gamma production or cytotoxicity.
      Furthermore, physical contact with iRBC can, in a proportion of donors, lead to
      NK cell cytoskeletal reorganization suggestive of functional interactions between
      the cells. These observations imply that individuals may vary in their ability to
      mount an innate immune response to malaria infection with obvious implications
      for disease resistance or susceptibility.

PMID- 16301655
TI  - Coordinate expression of CC chemokine ligand 5, granulysin, and perforin in CD8+
      T cells provides a host defense mechanism against Mycobacterium tuberculosis.
AB  - The ability of CD8+ T cells to kill intracellular pathogens depends upon their
      capacity to attract infected cells as well as their secretion of cytolytic and
      antimicrobial effector molecules. We examined the Ag-induced expression of three
      immune effector molecules contained within cytoplasmic granules of human CD8+ T
      cells: the chemokine CCL5, the cytolytic molecule perforin, and the antimicrobial
      protein granulysin. Macrophages infected with virulent Mycobacterium tuberculosis
      triggered the expression of CCL5 in CD8+ T cells only in donors with previous
      exposure to the tuberculosis bacteria, not in naive donors. Functionally, CCL5
      efficiently attracted M. tuberculosis-infected macrophages, but failed to exert
      direct antibacterial activity. Infected macrophages also triggered the expression
      of granulysin in CD8+ T cells, and granulysin was found to be highly active
      against drug-susceptible and drug-resistant M. tuberculosis clinical isolates.
      The vast majority of CCL5-positive cells coexpressed granulysin and perforin.
      Taken together, this report provides evidence that a subset of CD8+ T cells
      coordinately expresses CCL5, perforin and granulysin, thereby providing a host
      mechanism to attract M. tuberculosis-infected macrophages and kill the
      intracellular pathogen.

PMID- 16301656
TI  - Toll-IL-1 receptor domain-containing adaptor protein is critical for early lung
      immune responses against Escherichia coli lipopolysaccharide and viable
      Escherichia coli.
AB  - Pulmonary bacterial diseases are a leading cause of mortality in the U.S. Innate
      immune response is vital for bacterial clearance from the lung, and TLRs play a
      critical role in this process. Toll-IL-1R domain-containing adaptor protein
      (TIRAP) is a key molecule in the TLR4 and 2 signaling. Despite its potential
      importance, the role of TIRAP-mediated signaling in lung responses has not been
      examined. Our goals were to determine the role of TIRAP-dependent signaling in
      the induction of lung innate immune responses against Escherichia coli LPS and
      viable E. coli, and in lung defense against E. coli in mice. LPS-induced
      neutrophil sequestration; NF-kappaB translocation; keratinocyte cell-derived
      chemokine, MIP-2, TNF-alpha, and IL-6 expression; histopathology; and VCAM-1 and
      ICAM-1 expression were abolished in the lungs of TIRAP-/- mice. A cell-permeable
      TIRAP blocking peptide attenuated LPS-induced lung responses. Furthermore, immune
      responses in the lungs of TIRAP-/- mice were attenuated against E. coli compared
      with TIRAP+/+ mice. TIRAP-/- mice also had early mortality, higher bacterial
      burden in the lungs, and more bacterial dissemination following E. coli
      inoculation. Moreover, we used human alveolar macrophages to examine the role of
      TIRAP signaling in the human system. The TIRAP blocking peptide abolished LPS
      induced TNF-alpha, IL-6, and IL-8 expression in alveolar macrophages, whereas it
      attenuated E. coli-induced expression of these cytokines and chemokines. Taken
      together, this is the first study illustrating the crucial role of TIRAP in the
      generation of an effective early immune response against E. coli LPS and viable
      E. coli, and in lung defense against a bacterial pathogen.

PMID- 16301657
TI  - A model vaccine exploiting fungal mannosylation to increase antigen
      immunogenicity.
AB  - Ag mannosylation represents a promising strategy to augment vaccine
      immunogenicity by targeting Ag to mannose receptors (MRs) on dendritic cells.
      Because fungi naturally mannosylate proteins, we hypothesized that Ags engineered
      in fungi would have an enhanced capacity to stimulate T cell responses. Using the
      model Ag OVA, we generated proteins that differentially expressed N- and O-linked
      mannosylation in the yeast Pichia pastoris and compared them to their
      unglycosylated counterparts produced in Escherichia coli. We found that yeast
      derived OVA proteins containing N-linkages, extensive O-linkages, or both were
      more potent than the unmannosylated Ags at inducing OVA-specific CD4+ T cell
      proliferation. This elevated response to fungal Ags was inhibited by mannan,
      suggesting involvement of MRs. However, the macrophage MR (CD206) was not
      essential, because macrophage MR-deficient dendritic cells were fully competent
      in presenting yeast-derived OVA Ags. Thus, the use of fungal glycosylation to
      provide N-linked and/or extensive O-linked mannosylation increased the capacity
      of the model Ag OVA to stimulate Ag-specific T cell responses in an MR-dependent
      manner. These data have implications for vaccine design by providing proof of
      principle that yeast-derived mannosylation can enhance immunogenicity.

PMID- 16301658
TI  - The complex mechanism of antibody-mediated clearance of Bordetella from the lungs
      requires TLR4.
AB  - Although the antibacterial effects of Abs are well studied in in vitro systems,
      the in vivo effects of Abs cannot always be accurately predicted. Complicated
      cross-talk between different effector functions of Abs and various arms of the
      immune system can affect their activities in vivo. Using the mouse respiratory
      pathogen Bordetella bronchiseptica, we examined the mechanisms of Ab-mediated
      clearance of bacteria from the respiratory tract. Interestingly, although TLR4
      was not necessary for protective immunity following infection, it was required
      for rapid bacterial clearance in mice that were vaccinated or adoptively
      transferred Abs. TLR4 was important for the rapid recruitment of neutrophils that
      are necessary for Ab-mediated bacterial clearance via a mechanism that requires
      both FcgammaR and CR3. These data are consistent with a model in which TLR4
      mediated inflammatory responses aid in the recruitment of neutrophils, which
      phagocytose Ab- and complement-opsonized bacteria via FcgammaRs and CR3. Although
      pattern recognition receptors are known to be involved in innate immunity and the
      generation of adaptive immunity, their contributions to specific adaptive immune
      functions should be considered in ongoing efforts to improve vaccine-induced
      protective immunity.

PMID- 16301659
TI  - The exopolysaccharide alginate protects Pseudomonas aeruginosa biofilm bacteria
      from IFN-gamma-mediated macrophage killing.
AB  - The ability of Pseudomonas aeruginosa to form biofilms and cause chronic
      infections in the lungs of cystic fibrosis patients is well documented. Numerous
      studies have revealed that P. aeruginosa biofilms are highly refractory to
      antibiotics. However, dramatically fewer studies have addressed P. aeruginosa
      biofilm resistance to the host's immune system. In planktonic, unattached
      (nonbiofilm) P. aeruginosa, the exopolysaccharide alginate provides protection
      against a variety of host factors yet the role of alginate in protection of
      biofilm bacteria is unclear. To address this issue, we tested wild-type strains
      PAO1, PA14, the mucoid cystic fibrosis isolate, FRD1 (mucA22+), and the
      respective isogenic mutants which lacked the ability to produce alginate, for
      their susceptibility to human leukocytes in the presence and absence of IFN
      gamma. Human leukocytes, in the presence of recombinant human IFN-gamma, killed
      biofilm bacteria lacking alginate after a 4-h challenge at 37 degrees C.
      Bacterial killing was dependent on the presence of IFN-gamma. Killing of the
      alginate-negative biofilm bacteria was mediated through mononuclear cell
      phagocytosis since treatment with cytochalasin B, which prevents actin
      polymerization, inhibited leukocyte-specific bacterial killing. By direct
      microscopic observation, phagocytosis of alginate-negative biofilm bacteria was
      significantly increased in the presence of IFN-gamma vs all other treatments.
      Addition of exogenous, purified alginate to the alginate-negative biofilms
      restored resistance to human leukocyte killing. Our results suggest that although
      alginate may not play a significant role in bacterial attachment, biofilm
      development, and formation, it may play an important role in protecting mucoid P.
      aeruginosa biofilm bacteria from the human immune system.

PMID- 16301660
TI  - The impairment of CD8 responses limits the selection of escape mutations in acute
      hepatitis C virus infection.
AB  - Evasion from protective CD8 responses by mutations within immunodominant epitopes
      represents a potential strategy of HCV persistence. To investigate the
      pathogenetic relevance of this mechanism, a careful search for immunodominant CD8
      epitopes was conducted in six patients with chronic evolution of HCV infection by
      analyzing their global CD8 response with a panel of overlapping synthetic
      peptides covering the overall HCV sequence and by studying the CD8 frequency by
      tetramer staining. Immunodominant responses were followed longitudinally from the
      time of acute onset in relation to the evolution of the epitopic sequences.
      Although intensity of CD8 responses and frequency of HCV-specific CD8 cells
      declined over time in all patients, mutations emerged in only three of the six
      acute patients studied. Variant sequences were less efficiently recognized by CD8
      cells than parental epitopes and were poorly efficient in inducing a CD8 response
      in vitro. CD8 epitopes undergoing mutations were targeted by high avidity CD8
      cells more efficient in effector function. Our data support the view that
      immunodominant CD8 responses are affected by inhibitory mechanisms operating
      early after infection and that the emergence of escape mutations represents an
      additional mechanism of virus evasion from those CD8 responses that are
      functionally preserved.

PMID- 16301661
TI  - Lung NF-kappaB activation and neutrophil recruitment require IL-1 and TNF
      receptor signaling during pneumococcal pneumonia.
AB  - Pulmonary inflammation is an essential component of the host defense against
      Streptococcus pneumoniae infection of the lungs. The early response cytokines,
      TNF-alpha and IL-1, are rapidly induced upon microbial exposure. Mice deficient
      in all TNF- and IL-1-dependent signaling receptors were used to determine the
      roles of these cytokines during pneumococcal pneumonia. The deficiency of
      signaling receptors for TNF and IL-1 decreased bacterial clearance. Neutrophil
      recruitment to alveolar air spaces was impaired by receptor deficiency, as was
      pulmonary expression of the neutrophil chemokines KC and MIP-2. Because NF-kappaB
      mediates the expression of both chemokines, we assessed NF-kappaB activation in
      the lungs. During pneumococcal pneumonia, NF-kappaB proteins translocate to the
      nucleus and activate gene expression; these functions were largely abrogated by
      the deficiency of receptors for TNF-alpha and IL-1. Thus, the combined deficiency
      of TNF and IL-1 signaling reduces innate immune responses to S. pneumoniae in the
      lungs, probably due to essential roles for these receptors in activating NF
      kappaB.

PMID- 16301662
TI  - A predominant role for antibody in acquired immunity to chlamydial genital tract
      reinfection.
AB  - Acquired immunity to murine Chlamydia trachomatis genital tract reinfection has
      long been assumed to be solely dependent on cell-mediated immunity. However, in
      this study, we identify a previously unrecognized protective role for Ab.
      Immunity develops in Ab-deficient mice following the resolution of primary
      chlamydial genital infection. Subsequent depletion of CD4+ T cells, but not CD8+
      T cells, in those immune Ab-deficient mice before secondary infectious challenge,
      resulted in an infection that did not resolve. Passive immunization with immune
      (convalescent) serum conferred a marked level of protective immunity to
      reinfection, which was characterized by a striking decrease in bacterial
      shedding, from >100,000 inclusion forming units to fewer than 10 inclusion
      forming units, and a shortened duration of infection. Furthermore, mAbs to the
      chlamydial major outer membrane protein and LPS conferred significant levels of
      immunity to reinfection and reduced chlamydial shedding by >100-fold. Anti-heat
      shock protein 60 mAb had no protective effect. In contrast to the marked
      protective efficacy of immune serum on reinfection, the course of primary
      infection was essentially unaltered by the passive transfer of immune serum. Our
      results convincingly demonstrate that Abs contribute importantly to immunity to
      chlamydial genital tract reinfection, and that Ab-mediated protection is highly
      dependent on CD4+ T cell-mediated adaptive changes that occur in the local
      genital tract tissues during primary infection. These results impact our
      understanding of immunity to chlamydial genital infection and may provide
      important insight into vaccine development.

PMID- 16301663
TI  - Molecular and cellular basis of the retrovirus resistance in I/LnJ mice.
AB  - Previously, we showed that IFN-gamma elicited by mouse mammary tumor virus (MMTV)
      infection in I/LnJ mice stimulated production of virus-neutralizing Abs, mostly
      of the IgG2a isotype. These Abs coated virions secreted by infected I/LnJ cells,
      and thus completely prevented virus transmission to offspring. However, the
      mechanism of virus neutralization by isotype-specific Abs remained unknown. Ab
      coating is capable of blocking virus infection by interfering with receptor-virus
      binding, by virus opsonization, by complement activation, and via FcgammaR
      mediated effector mechanisms. The aim of the studies described in this work was
      to uncover the cellular basis of anti-virus Ab production, to evaluate the
      importance of the IgG2a subclass of IgGs in virus neutralization, and to
      investigate which of the blocking mechanisms plays a role in virus
      neutralization. We showed that I/LnJ-derived bone marrow cells, specifically IFN
      gamma-producing CD4+ T cells, were key cells conferring resistance to MMTV
      infection in susceptible mice upon transfer. We also established that a unique
      bias in the subclass selection toward the IgG2a isotype in infected I/LnJ mice
      was not due to their potent neutralizing ability, as anti-virus Abs of other
      isotypes were also able to neutralize the virus, but were a product of virally
      induced IFN-gamma. Finally, we demonstrated that F(ab')2 of anti-MMTV IgGs
      neutralized the virus as efficiently as total IgGs, suggesting that Ab-mediated
      interference with viral entry is the sole factor inhibiting virus replication in
      I/LnJ mice. We propose and discuss possible mechanisms by which infected I/LnJ
      mice eradicate retrovirus.

PMID- 16301664
TI  - Diversity in the acute CD8 T cell response to vaccinia virus in humans.
AB  - Orthopoxviruses have complex proteomes. Infection provokes a brisk CD8 response,
      which is required in some systems for recovery from primary infection. Little is
      known concerning the Ags and epitopes recognized by CD8 T cells. We examined the
      fine specificity of cloned and bulk human vaccinia-specific CD8 CTL by expressing
      polypeptide fragments from a library of vaccinia genomic DNA. This epitope
      discovery method emphasizes virus-specific biological activity, as the responder
      cells are all reactive with whole vaccinia virus. Sixteen novel epitopes,
      restricted by several HLA A and B alleles, were defined to the nomamer peptide
      level in diverse vaccinia open reading frames. An additional seven epitope were
      mapped to short regions of vaccinia proteins. Targets of the CD8 response
      included proteins assigned to structural, enzymatic, transcription factor, and
      immune evasion functions, and included members of all viral kinetic classes. Most
      epitopes were conserved in other orthopoxviruses. Responses to at least 18
      epitopes were detected within a single blood sample, revealing a surprising
      degree of diversity. These epitopes will be useful in natural history studies of
      CD8 responses to vaccinia, a nonpersisting virus with long-term memory, and in
      the design and evaluation of attenuated and replication-incompetent vaccinia
      strains being tested for variola and monkeypox prevention and for the delivery of
      heterologous Ags.

PMID- 16301665
TI  - Cationic polypeptides are required for anti-HIV-1 activity of human vaginal
      fluid.
AB  - Mucosal surfaces of the vagina are the portals for heterosexual transmission of
      HIV-1 and therefore play a fundamental role in the pathogenesis of primary
      infection. In the search for direct biological evidence for the role of human
      vaginal fluid in innate host defense, we characterized the anti-HIV-1 function of
      cationic polypeptides within minimally manipulated vaginal fluid. In the current
      study we revealed that vaginal fluid confers intrinsic anti-HIV-1 properties
      against both X4 and R5 strains of HIV-1 and could protect against HIV-1 infection
      and reduce proviral genome integration in organotypic cultures of human
      cervicovaginal tissue. The majority of this activity was contained in the
      cationic polypeptide fraction, and the depletion of cationic polypeptides using a
      selective cation exchange resin ablated most of the intrinsic activity against
      HIV-1. By adding the cationic polypeptide fraction to depleted vaginal fluid, we
      were able to restore activity against HIV-1. Using a proteomic approach, we
      identified 18 cationic polypeptides within vaginal fluid, nearly all of which are
      either known antimicrobials or have other purported roles in host defense.
      Interestingly, physiologic concentrations of 13 of the cationic polypeptides were
      not active alone against HIV-1, yet in concert they partially restored the anti
      HIV-1 activity of cation-depleted vaginal fluid. These results suggest that
      synergism between cationic polypeptides is complex, and full anti-HIV-1 activity
      probably involves the aggregate of the cationic peptides and proteins in vaginal
      fluid.

PMID- 16301666
TI  - Human NK cells inhibit cytomegalovirus replication through a noncytolytic
      mechanism involving lymphotoxin-dependent induction of IFN-beta.
AB  - NK cells play a key role in host defense against the beta-herpesvirus CMV through
      perforin-dependent cytolysis. In this study, we show that human NK cells can also
      control human CMV (HCMV) infection by a noncytolytic mechanism involving
      induction of IFN-beta in the virus-infected cell. Both IL-2-activated primary NK
      cells and an IL-2-dependent NK cell line (NK-92) exhibited potent, noncytolytic
      anti-HCMV activity at very low E:T cell ratios (<0.1:1). Activated NK cells
      expressed lymphotoxin (LT)alphabeta on their cell surface, and secreted LTalpha
      and TNF, all of which contributed to the NF-kappaB-dependent release of IFN-beta
      from infected fibroblasts. IFN-beta produced by fibroblasts and NK cell-produced
      IFN-gamma combined to inhibit HCMV replication after immediate early gene
      expression. These results highlight an efficient mechanism used by NK cells to
      activate IFN-beta expression in the infected target cell that contributes to the
      arrest of virion production and virus spread without cellular elimination.

PMID- 16301667
TI  - Human CD4+ T cells induced by synthetic peptide malaria vaccine are comparable to
      cells elicited by attenuated Plasmodium falciparum sporozoites.
AB  - Peptide vaccines containing minimal epitopes of protective Ags provide the
      advantages of low cost, safety, and stability while focusing host responses on
      relevant targets of protective immunity. However, the limited complexity of
      malaria peptide vaccines raises questions regarding their equivalence to immune
      responses elicited by the irradiated sporozoite vaccine, the "gold standard" for
      protective immunity. A panel of CD4+ T cell clones was derived from volunteers
      immunized with a peptide vaccine containing minimal T and B cell epitopes of the
      Plasmodium falciparum circumsporozoite protein to compare these with previously
      defined CD4+ T cell clones from volunteers immunized with irradiated P.
      falciparum sporozoites. As found following sporozoite immunization, the majority
      of clones from the peptide-immunized volunteers recognized the T* epitope, a
      predicted universal T cell epitope, in the context of multiple HLA DR and DQ
      molecules. Peptide-induced T cell clones were of the Th0 subset, secreting high
      levels of IFN-gamma as well as variable levels of Th2-type cytokines (IL-4, IL
      6). The T* epitope overlaps a polymorphic region of the circumsporozoite protein
      and strain cross-reactivity of the peptide-induced clones correlated with
      recognition of core epitopes overlapping the conserved regions of the T* epitope.
      Importantly, as found following sporozoite immunization, long-lived CD4+ memory
      cells specific for the T* epitope were detectable 10 mo after peptide
      immunization. These studies demonstrate that malaria peptides containing minimal
      epitopes can elicit human CD4+ T cells with fine specificity and potential
      effector function comparable to those elicited by attenuated P. falciparum
      sporozoites.

PMID- 16301668
TI  - Preferential targeting of CD4-CCR5 complexes with bifunctional inhibitors: a
      novel approach to block HIV-1 infection.
AB  - Two receptors, CD4 and one of several chemokine receptors, are required for
      cellular HIV-1 infection, with CCR5 being the main coreceptor for macrophage
      tropic strains. We have designed bifunctional fusion proteins, consisting of
      RANTES/CCL5 and a single-chain Fv Ab fragment against CD4 to simultaneously block
      CD4 and CCR5. The fusion proteins bind to both receptors, compete with
      RANTES/CCL5 binding, and induce down-modulation of CCR5 approximately 10 times
      more efficiently on CD4+ compared with CD8+ T cells. Moreover, after short
      incubation and subsequent washout, a significant down-modulation of CCR5 was only
      seen with the fusion proteins and only on CD4+ cells, but not with unmodified
      RANTES or on CD4- cells, indicating a preferential targeting of CCR5 on CD4+ T
      cells. The fusion proteins block M-tropic HIV infection more efficiently than
      RANTES/CCL5 and CD4 Abs alone or in combination. To our knowledge this is the
      first report of simultaneous blockade of an HIV-1 receptor and coreceptor with
      bifunctional inhibitors.

PMID- 16301669
TI  - Viral inhibition of IL-1- and neutrophil elastase-induced inflammatory responses
      in bronchial epithelial cells.
AB  - Previously, we elucidated the intracellular mechanisms by which neutrophil
      elastase (NE) up-regulates inflammatory gene expression in bronchial epithelial
      cells. In this study, we examine the effects of both IL-1 and NE on inflammatory
      gene expression in 16HBE14o- bronchial epithelial cells and investigate
      approaches to abrogate these inflammatory responses. IL-1 induced IL-8 protein
      production in time- and dose-dependent fashions, an important observation given
      that IL-8 is a potent neutrophil chemoattractant and a key inflammatory mediator.
      IL-1 and NE were shown to activate the p38 MAPK pathway in 16HBE14o- cells.
      Western blot analysis demonstrated IL-1R-associated kinase 1 (IRAK-1) degradation
      in response to stimulation with both IL-1 and NE. In addition, the expression of
      dominant negative IRAK-1 (IRAK-1delta), IRAK-2delta, or IRAK-4delta inhibited IL
      1- and NE-induced NF-kappaB-linked reporter gene expression. Dominant negative
      versions of the intracellular adaptor proteins MyD88 (MyD88delta) and MyD88
      adaptor-like (Mal P/H) abrogated NE-induced NF-kappaB reporter gene expression.
      In contrast, only MyD88delta was found to inhibit IL-1-induced NF-kappaB reporter
      activity. We also investigated the vaccinia virus proteins, A46R and A52R, which
      have been shown to antagonize IL-1 signaling. Transfection with A46R or A52R cDNA
      inhibited IL-1- and NE-induced NF-kappaB and IL-8R gene expression and IL-8
      protein production in primary and transformed bronchial epithelial cells.
      Furthermore, cytokine array studies demonstrated that IL-1 and NE can up-regulate
      the expression of IL-6, oncostatin M, epithelial cell-derived neutrophil
      activating peptide-78, growth-related oncogene family members, vascular
      endothelial growth factor, and GM-CSF, with induction of these proteins inhibited
      by the viral proteins. These findings identify vaccinia virus proteins as
      possible therapeutic agents for the manifestations of several inflammatory lung
      diseases.

PMID- 16301670
TI  - Impaired FcepsilonRI-dependent gene expression and defective eicosanoid and
      cytokine production as a consequence of Fyn deficiency in mast cells.
AB  - Fyn kinase is a key contributor in coupling FcepsilonRI to mast cell
      degranulation. A limited macroarray analysis of FcepsilonRI-induced gene
      expression suggested potential defects in lipid metabolism, eicosanoid and
      glutathione metabolism, and cytokine production. Biochemical analysis of these
      responses revealed that Fyn-deficient mast cells failed to secrete the
      inflammatory eicosanoid products leukotrienes B4 and C4, the cytokines IL-6 and
      TNF, and chemokines CCL2 (MCP-1) and CCL4 (MIP-1beta). FcepsilonRI-induced
      generation of arachidonic acid and normal induction of cytokine mRNA were
      defective. Defects in JNK and p38 MAPK activation were observed, whereas ERK1/2
      and cytosolic phospholipase A2 (S505) phosphorylation was normal. Pharmacological
      studies revealed that JNK activity was associated with generation of arachidonic
      acid. FcepsilonRI-mediated activation of IkappaB kinase beta and IkappaBalpha
      phosphorylation and degradation was defective resulting in a marked decrease of
      the nuclear NF-kappaB DNA binding activity that drives IL-6 and TNF production in
      mast cells. However, not all cytokine were affected, as IL-13 production and
      secretion was enhanced. These studies reveal a major positive role for Fyn kinase
      in multiple mast cell inflammatory responses and demonstrate a selective negative
      regulatory role for certain cytokines.

PMID- 16301671
TI  - Potentiation of caspase-1 activation by the P2X7 receptor is dependent on TLR
      signals and requires NF-kappaB-driven protein synthesis.
AB  - The proinflammatory cytokines IL-1beta and IL-18 are inactive until cleaved by
      the enzyme caspase-1. Stimulation of the P2X7 receptor (P2X7R), an ATP-gated ion
      channel, triggers rapid activation of caspase-1. In this study we demonstrate
      that pretreatment of primary and Bac1 murine macrophages with TLR agonists is
      required for caspase-1 activation by P2X7R but it is not required for activation
      of the receptor itself. Caspase-1 activation by nigericin, a K+/H+ ionophore,
      similarly requires LPS priming. This priming by LPS is dependent on protein
      synthesis, given that cyclohexamide blocks the ability of LPS to prime
      macrophages for activation of caspase-1 by the P2X7R. This protein synthesis is
      likely mediated by NF-kappaB, as pretreatment of cells with the proteasome
      inhibitor MG132, or the IkappaB kinase inhibitor Bay 11-7085 before LPS
      stimulation blocks the ability of LPS to potentiate the activation of caspase-1
      by the P2X7R. Thus, caspase-1 regulation in macrophages requires inflammatory
      stimuli that signal through the TLRs to up-regulate gene products required for
      activation of the caspase-1 processing machinery in response to K+-releasing
      stimuli such as ATP.

PMID- 16301672
TI  - Inhibitory effects of chloride on the activation of caspase-1, IL-1beta
      secretion, and cytolysis by the P2X7 receptor.
AB  - The P2X7 receptor (P2X7R) is an ATP-gated cation channel that activates caspase-1
      leading to the maturation and secretion of IL-1beta. Because previous studies
      indicated that extracellular Cl- exerts a negative allosteric effect on ATP
      gating of P2X7R channels, we tested whether Cl- attenuates the P2X7R-->caspase-1-
      >IL-1beta signaling cascade in murine and human macrophages. In Bac1 murine
      macrophages, substitution of extracellular Cl- with gluconate produced a 10-fold
      increase in the rate and extent of ATP-induced IL-1beta processing and secretion,
      while reducing the EC50 for ATP by 5-fold. Replacement of Cl- with gluconate also
      increased the potency of ATP as an inducer of mature IL-1beta secretion in
      primary mouse bone marrow-derived macrophages and in THP-1 human
      monocytes/macrophages. Our observations were consistent with actions of Cl- at
      three levels: 1) a negative allosteric effect of Cl-, which limits the ability of
      ATP to gate the P2X7R-mediated cation fluxes that trigger caspase-1 activation;
      2) an intracellular accumulation of Cl- via nonselective pores induced by P2X7R
      with consequential repression of caspase-1-mediated processing of IL-1beta; and
      3) a facilitative effect of Cl- substitution on the cytolytic release of
      unprocessed pro-IL-1beta that occurs with sustained activation of P2X7R. This
      cytolysis was repressed by the cytoprotectant glycine, permitting dissociation of
      P2X7R-regulated secretion of mature IL-1beta from the lytic release of pro-IL
      1beta. These results suggest that under physiological conditions P2X7R are
      maintained in a conformationally restrained state that limits channel gating and
      coupling of the receptor to signaling pathways that regulate caspase-1.

PMID- 16301673
TI  - Protein kinase Ctheta controls Th1 cells in experimental autoimmune
      encephalomyelitis.
AB  - Molecules that regulate encephalitogenic T cells are of interest for multiple
      sclerosis. In this study we show that protein kinase Ctheta (PKCtheta) is
      critical for the development of Ag-specific Th1 cells in experimental allergic
      encephalomyelitis (EAE), a model of multiple sclerosis. PKCtheta-deficient mice
      immunized with myelin oligodendrocyte glycoprotein failed to develop cell
      infiltrates and Th1 cytokines in the CNS and were resistant to the development of
      clinical EAE. CD4 T cells became primed and accumulated in secondary lymphoid
      organs in the absence of PKCtheta, but had severely diminished IFN-gamma, TNF,
      and IL-17 production. Increasing Ag exposure and inflammatory conditions failed
      to induce EAE in PKCtheta-deficient mice, showing a profound defect in the myelin
      oligodendrocyte glycoprotein-reactive T cell population. These data provide
      evidence of a pivotal role for PKCtheta in the generation and effector function
      of autoimmune Th1 cells.

PMID- 16301674
TI  - Resistance of collagenase-2 (matrix metalloproteinase-8)-deficient mice to TNF
      induced lethal hepatitis.
AB  - Acute fulminant liver failure is a serious worldwide health problem. Despite
      maximal supportive intensive care treatment, the disease offers a poor prognosis,
      with mortality rates of >80%. We have previously shown that a broad-spectrum
      inhibitor of matrix metalloproteinases (MMPs) confers complete protection in a
      mouse model of TNF-induced lethal hepatitis, thereby suggesting the possibility
      of protecting cancer patients against the deleterious side effects of TNF
      therapy. In our search for the individual matrix metalloproteinases involved, we
      found that the recently generated MMP-8-deficient mice are significantly
      protected against TNF-induced acute hepatitis. In contrast to their wild-type
      counterparts, MMP-8-null mice display very little hepatocyte necrosis and
      apoptosis, resulting in a much better survival outcome. We found that these
      animals clearly display impaired leukocyte influx into the liver and no release
      of the neutrophil-specific, LPS-induced CXC chemokine. Our findings provide
      evidence that MMP-8 plays an essential role in acute liver failure and might be a
      promising new target for the treatment for this illness.

PMID- 16301675
TI  - A role for the neuronal protein collapsin response mediator protein 2 in T
      lymphocyte polarization and migration.
AB  - The semaphorin-signaling transducer collapsin response mediator protein 2 (CRMP2)
      has been identified in the nervous system where it mediates Sema3A-induced growth
      cone navigation. In the present study, we provide first evidence that CRMP2 is
      present in the immune system and plays a critical role in T lymphocyte function.
      CRMP2 redistribution at the uropod in polarized T cells, a structural support of
      lymphocyte motility, suggests that it may regulate T cell migration. This was
      evidenced in primary T cells by small-interfering RNA-mediated CRMP2 gene
      silencing and blocking Ab, as well as CRMP2 overexpression in Jurkat T cells
      tested in a chemokine- and semaphorin-mediated transmigration assay. Expression
      analysis in PBMC from healthy donors showed that CRMP2 is enhanced in cell
      subsets bearing the activation markers CD69+ and HLA-DR+. Heightened expression
      in T lymphocytes of patients suffering from neuroinflammatory disease with
      enhanced T cell-transmigrating activity points to a role for CRMP2 in
      pathogenesis. The elucidation of the signals and mechanisms that control this
      pathway will lead to a better understanding of T cell trafficking in
      physiological and pathological situations.

PMID- 16301676
TI  - Hepatic ischemia/reperfusion injury involves functional TLR4 signaling in
      nonparenchymal cells.
AB  - Endogenous ligands from damaged cells, so-called damage-associated molecular
      pattern molecules, can activate innate immunity via TLR4 signaling. Hepatic warm
      ischemia and reperfusion (I/R) injury and inflammation is largely TLR4 dependent.
      We produced TLR4 chimeric mice to assess whether the TLR4-dependent injury
      required TLR4 expression on liver parenchymal or nonparenchymal cells. Chimeric
      mice were produced by adoptive transfer of donor bone marrow cells into
      irradiated recipient animals using reciprocal combinations of TLR4 wild-type (WT;
      C3H/HeOuj) and TLR4 mutant (C3H/HeJ) mouse bone marrow. Wild-type chimeric mice
      bearing TLR4 mutant hemopoietic cells and TLR4 mutant mice transplanted with
      their own bone marrow-derived cells were protected from hepatic I/R and exhibited
      decreased JNK and NF-kappaB activation compared with WT chimeric mice
      transplanted with their own bone marrow. In contrast, TLR4 mutant mice
      transplanted with TLR4 WT bone marrow were not protected from liver I/R and
      demonstrated pronounced increases in JNK and NF-kappaB activation when compared
      with autochthonous transplanted mutant mice. In addition, depletion of phagocytes
      taking up gadolinium chloride failed to provide any additional protection to TLR4
      mutant mice, but substantially reduced damage in WT mice after hepatic I/R.
      Together, these results demonstrate that TLR4 engagement on actively phagocytic
      nonparenchymal cells such as Kupffer cells is required for warm I/R-induced
      injury and inflammation in the liver.

PMID- 16301677
TI  - Evidence for multiple shared antigenic determinants within Ro60 and other lupus
      related ribonucleoprotein autoantigens in human autoimmune responses.
AB  - Ab responses directed against several ribonucleoprotein (RNP) Ags are a
      characteristic feature of systemic lupus erythematosus (SLE). Previous work in
      our laboratory using mouse model systems had revealed that both epitope spreading
      and inherent cross-reactivity between ribonucleoproteins contributes to the
      observed multiple specificities in autoimmune sera. We have now extended these
      studies to human autoimmune responses. Using purified polyclonal and mAbs derived
      from SLE patients, cross-reactivity between Ro60 and SmD was demonstrated. The
      cross-reactive epitope was mapped to nonhomologous regions on Ro60(481-505) and
      SmD(88-102). Five mAbs specifically recognized apoptotic cells, demonstrated
      variable levels of cross-reactivity toward other nonhomologous ribonucleoprotein
      targets and bound multiple, nonoverlapping and nonhomologous epitopes on Ro60.
      Our study demonstrates that cross-reactivity between frequently targeted
      autoantigens is an important aspect of human systemic autoimmune responses. The
      presence of multiple cross-reactive epitopes on Ro60 might be important for the
      generation of anti-Ro60 Ab in SLE patients and in normal individuals displaying
      no evidence of clinical disease.

PMID- 16301678
TI  - T cell-regulated neutrophilic inflammation in autoinflammatory diseases.
AB  - Previous studies of acute generalized exanthematous pustulosis, a peculiar drug
      hypersensitivity reaction, suggested that CXCL8-producing T cells regulate
      sterile, polymorphonuclear neutrophil-rich skin inflammations. In this study, we
      test the hypothesis of whether CXCL8-producing T cells are present in
      autoinflammatory diseases like pustular psoriasis and Behcet's disease.
      Immunohistochemistry of normal skin revealed few CD4+ and CD8+ T cells, few
      CXCL8+ cells, and no neutrophilic infiltration, whereas in acute exacerbations of
      atopic dermatitis, numerous CD4+ T cells but few CD8+ T cells, neutrophils, or
      CXCL8+ cells were detected. In contrast, a pronounced infiltration of neutrophils
      and of predominantly CD4+ T cells was observed in skin biopsies from pustular
      psoriasis, Behcet's disease, and acute generalized exanthematous pustulosis, with
      infiltrating T cells strongly positive for CXCL8 and the chemokine receptor CCR6.
      Skin-derived T cell clones from pustular skin reactions were positive for CCR6
      but negative for CCR8 and secreted high amounts of CXCL8 and GM-CSF, often
      together with IFN-gamma and TNF-alpha after in vitro stimulation. Moreover, some
      skin-derived T cell clones from Behcet's disease and from pustular psoriasis
      predominantly produced CXCL8 and GM-CSF, but failed to secrete IL-5 and IFN
      gamma. These cells might represent a particular subset as they differ from both
      Th1 as well as Th2 T cells and are associated with a unique, neutrophil-rich
      sterile inflammation. Our findings suggest that CXCL8/GM-CSF-producing T cells
      may orchestrate neutrophil-rich pathologies of chronic autoinflammatory diseases
      like pustular psoriasis and Behcet's disease.

PMID- 16301679
TI  - Enhancement of adenovirus-mediated gene delivery to rheumatoid arthritis
      synoviocytes and synovium by fiber modifications: role of arginine-glycine
      aspartic acid (RGD)- and non-RGD-binding integrins.
AB  - Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) do not express the
      coxsackie-adenovirus (Ad) receptor and are poorly permissive to Ad serotype 5
      (Ad5). Genetically modified, coxsackie-Ad receptor-independent Ad5 vectors were
      studied for gene delivery in human RA FLS and synovium explants and murine
      collagen-induced arthritis. Short-fiber Ad5 vectors with seven fiber shaft
      repeats Ad5GFP-R7-knob, Ad5GFP-R7-arginine-glycine-aspartic acid (RGD) (RGD
      liganded), and Ad5GFPDeltaknob (knob-deleted) were compared with Ad5GFP-FiWT, a
      conventional wild-type (WT) Ad5 vector. Gene transfer by Ad5GFP-R7-knob and
      Ad5GFP-R7-RGD was 40- to 50-fold and 25-fold higher, respectively, than Ad5GFP
      FiWT in FLS. Ad5GFPDeltaknob was more efficacious than its knob-bearing version
      Ad5GFP-R7-knob in FLS transduction. Virus attachment and entry required RGD- and
      LDV-binding integrins including alpha(v), alpha(v)beta3, a(v)beta5, and beta1.
      Ad5GFP-R7-knob infection of FLS was partially neutralized by synovial fluid (SF),
      but remained 30- to 40-fold higher than Ad5GFP-FiWT in the presence of SF.
      Ad5GFPDeltaknob was partially neutralized by SF at low virus input, but escaped
      viral neutralization by SF at higher virus input. Gene transfer to human synovium
      ex vivo explants and murine collagen-induced arthritis in vivo was also more
      efficient with short fiber-modified vectors (with and without the knob domain)
      than Ad5GFPFiWT. Gene transfer by short fiber-modified vectors was enhanced by
      inflammatory cytokines in vitro and in the presence of inflammation in murine
      synovium in vivo. Our data indicated that the highly efficient gene delivery RA
      was mediated by RGD- and non-RGD-binding integrins and enhanced by inflammation.
      Short fiber modifications with knob ablation may be a strategy to enhance gene
      delivery, reducing vector dose and vector-induced inflammation and toxicity.

PMID- 16301680
TI  - Cell- rather than antibody-mediated immunity leads to the development of profound
      thrombocytopenia during experimental Plasmodium berghei malaria.
AB  - Experimental malarial thrombocytopenia can reach life-threatening levels and is
      believed to be due to Abs targeting platelets for destruction by the
      reticuloendothelial system. However, we report that Abs account for at most 15%
      of platelet destruction as Plasmodium berghei-infected B cell-deficient mice
      exhibited profound thrombocytopenia (83%) as did C57BL/6 controls (98%). Further,
      no significant increase in Abs bound to intact platelets was observed during
      infection. P. berghei infection can enhance the activity of anti-platelet Abs as
      indicated by a significantly (p < 0.005) increased thrombocytopenia on day 4 of
      infection in mice that were administered a low dose anti-CD41 mAb compared with
      rat IgG1-injected controls. RAG1-/- and CD4- plus CD8-deficient mice were
      markedly protected from thrombocytopenia (p < 0.005) and malarial pathogenesis.
      CD8- or TCRgammadelta-deficient mice were not protected from thrombocytopenia and
      CD4-deficient mice were modestly protected. RAG1-/- mice exhibited significantly
      (p < 0.05) lower levels of plasma TNF, IFN-gamma, and IL-12 during infection.
      IFNgamma-/- and IL-12-/- mice exhibited increased survival but similar
      thrombocytopenia to C57BL/6 controls. Collectively, these data indicate that
      thrombocytopenia is necessary but not sufficient for malarial pathogenesis and
      Abs are not the major contributors to malarial thrombocytopenia. Rather, we
      propose that both CD4+ and CD8+ T cell populations play key roles in malarial
      thrombocytopenia; a complex bidirectional interaction between cell-mediated
      immunity and platelets exists during experimental severe malaria that regulates
      both responses.

PMID- 16301681
TI  - Increased expression of integrin alpha(v)beta3 contributes to the establishment
      of autocrine TGF-beta signaling in scleroderma fibroblasts.
AB  - The constitutive secretion of latent TGF-beta by many cell types in culture
      suggests that extracellular mechanisms to control the activity of this potent
      cytokine are important in the pathogenesis of the diseases in which this cytokine
      may be involved, including fibrotic disorders. In this study, we focused on the
      alpha(v)beta3 integrin, which is recently demonstrated to function as an active
      receptor for latent TGF-beta1 through its interaction with latency-associated
      peptide-beta1, and investigated the involvement of this integrin in the
      pathogenesis of scleroderma. Scleroderma fibroblasts exhibited increased
      alpha(v)beta3 expression compared with normal fibroblasts in vivo and in vitro.
      In scleroderma fibroblasts, ERK pathway was constitutively activated and such
      abnormality induced the up-regulation of alpha(v)beta3. Transient overexpression
      of alpha(v)beta3 in normal fibroblasts induced the increase in the promoter
      activity of human alpha2(I) collagen gene and the decrease in that of human MMP-1
      gene. These effects of alpha(v)beta3 were almost completely abolished by the
      treatment with anti-TGF-beta Ab or TGF-beta1 antisense oligonucleotide.
      Furthermore, the addition of anti-alpha(v)beta3) Ab reversed the expression of
      type I procollagen protein and MMP-1 protein, the promoter activity of human
      alpha2(I) collagen gene, and the myofibroblastic phenotype in scleroderma
      fibroblasts. These results suggest that the up-regulated expression of
      alpha(v)beta3 contributes to the establishment of autocrine TGF-beta loop in
      scleroderma fibroblasts, and this integrin is a potent target for the treatment
      of scleroderma.

PMID- 16301682
TI  - Staphylococcal protein a deletes B-1a and marginal zone B lymphocytes expressing
      human immunoglobulins: an immune evasion mechanism.
AB  - Protein A (SpA) of Staphylococcus aureus is endowed with the capacity to interact
      with the H chain variable region (V(H)) of human Abs and to target >40% of B
      lymphocytes. To investigate whether this property represents a virulence factor
      and to determine the in vivo consequences of the confrontation of SpA with B
      lymphocytes, we used transgenic mice expressing fully human Abs. We found that
      administration of soluble SpA reduces B-1a lymphocytes of the peritoneal cavity
      and marginal zone B lymphocytes of the spleen, resulting in a markedly deficient
      type 2 humoral response. Single-cell PCR analysis and sequencing of the Ab V(H)
      gene repertoire revealed a significant reduction of V(H)3+ marginal zone B cells.
      Since the two B lymphocyte subsets targeted are involved in innate immune
      functions, our data suggest that crippling of humoral immunity by S. aureus
      represents an immune evasion mechanism that may aggravate recurrent infections.

PMID- 16301683
TI  - Tolerogenic treatment of lupus mice with consensus peptide induces Foxp3
      expressing, apoptosis-resistant, TGFbeta-secreting CD8+ T cell suppressors.
AB  - Lupus-prone (NZB x NZW)F1 mice spontaneously develop elevated titers of anti-DNA
      Abs that contain T cell determinants in their V(H) regions. We have previously
      shown that tolerization with an artificial peptide based on these T cell
      determinants (pConsensus (pCons)) can block production of anti-DNA Abs and
      prolong survival of the mice. In this study, we show that this protection depends
      in part on the generation of peripheral TGFbeta- and Foxp3-expressing inhibitory
      CD8+ (Ti) cells. These CD8+ Ti cells suppress anti-DNA IgG production both in
      vitro and in vivo and require up-regulated expression of both Foxp3 and TGFbeta
      to exert their suppressive function, as indicated by microarray analyses, small
      interfering RNA inhibition studies, and blocking experiments. Additionally, CD8+
      Ti cells from pCons-tolerized mice were longer-lived suppressors that up
      regulated expression of Bcl-2 and were more resistant to apoptosis than similar
      cells from naive mice. These data indicate that clinical suppression of
      autoimmunity after administration of pCons depends in part on the generation of
      CD8+ Ti cells that suppress secretion of anti-DNA Ig using mechanisms that
      include Foxp3, TGFbeta, and resistance to apoptosis.

PMID- 16301684
TI  - Effector function of diabetogenic CD4 Th1 T cell clones: a central role for TNF
      alpha.
AB  - Effector function of T cells in autoimmune diabetes has been widely studied with
      mixed populations of lymphoid T cells stimulated ex vivo, but this approach does
      not permit evaluation of the contribution by a single T cell clone in the
      inflammatory site during pathogenesis. We have investigated cytokine production
      both in vitro and in vivo in a panel of diabetogenic CD4 Th1 T cell clones
      derived from the NOD mouse. SuperArray analysis showed a common pattern of mRNA
      expression for inflammatory cytokines and receptors in vitro after TCR
      stimulation. Ex vivo intracellular cytokine staining demonstrated that two
      important inflammatory cytokines, IFN-gamma and TNF-alpha, were being made by
      these T cells recovered from the pancreas 6 days following adoptive transfer. TNF
      alpha produced in the pancreas by pathogenic T cell clones and recruited
      macrophages was not the membrane-bound form. Secreted TNF-alpha can lead to
      production of multiple inflammatory chemokines, as were observed in the
      pathogenic clones by intracellular cytokine staining. Our results not only define
      the nature of an inflammatory cytokine response critical to development of
      diabetes, but also suggest its role in the regulation of other events during
      pathogenesis induced by CD4 T cells. Similar analyses in other models
      demonstrated that disease induced by CD4 T cell clones closely resembles
      spontaneous autoimmune diabetes in which both CD4 and CD8 T cells are required.
      Thus, cloned T cells in effect amplify effector function of T cells which
      otherwise may be difficult to detect without ex vivo stimulation.

PMID- 16301685
TI  - Analysis of the cellular mechanism of antitumor responses and autoimmunity in
      patients treated with CTLA-4 blockade.
AB  - We have demonstrated previously that the administration of CTLA-4 blockade has
      mediated objective cancer regression and autoimmunity in patients with metastatic
      melanoma. To explore the mechanism of these in vivo effects, we have studied the
      changes in lymphocyte phenotype and function in patients receiving anti-CTLA-4 Ab
      (MDX-010). Patients with stage IV melanoma or renal cell cancer were treated
      every 3 wk with an anti-CTLA-4 Ab with or without peptide immunization. Pheresis
      samples were analyzed using flow cytometry to determine lymphocyte cell surface
      markers. Gene expression analyses and proliferation assays were conducted on
      purified T cell subsets. Anti-CTLA-4 Ab did not inhibit the suppressive activity
      of CD4+CD25+ cells in vitro or in vivo. In addition, there was no decrease in the
      expression of CD4+CD25+ cells in whole PBMC, nor a decrease in Foxp3 gene
      expression in the CD4+ or CD4+CD25+ purified cell populations posttreatment. The
      percentage of CD4+, CD8+, CD4+CD25+, and CD4+CD25- T cells in PBMC expressing the
      activation marker HLA-DR increased following anti-CTLA-4 Ab administration.
      Therefore, our results suggest that the antitumor effects of CTLA-4 blockade are
      due to increased T cell activation rather than inhibition or depletion of T
      regulatory cells.

PMID- 16301686
TI  - Analysis of GAD65 autoantibodies in Stiff-Person syndrome patients.
AB  - Autoantibodies to the 65-kDa isoform of glutamate decarboxylase GAD65 (GAD65Ab)
      are strong candidates for a pathological role in Stiff-Person syndrome (SPS). We
      have analyzed the binding specificity of the GAD65Ab in serum and cerebrospinal
      fluid (CSF) of 12 patients with SPS by competitive displacement studies with
      GAD65-specific rFab-derived from a number of human and mouse mAbs specific for
      different determinants on the Ag. We demonstrate considerable differences in the
      epitope specificity when comparing paired serum and CSF samples, suggesting local
      stimulation of B cells in the CSF compartment of these patients. Moreover, these
      autoantibodies strongly inhibit the enzymatic activity of GAD65, thus blocking
      the formation of the neurotransmitter gamma-aminobutyric acid. The capacity of
      the sera to inhibit the enzymatic activity of GAD65 correlated with their binding
      to a conformational C-terminal Ab epitope. Investigation of the inhibitory
      mechanism revealed that the inhibition could not be overcome by high
      concentrations of glutamate or the cofactor pyridoxal phosphate, suggesting a
      noncompetitive inhibitory mechanism. Finally, we identified a linear epitope on
      amino acids residues 4-22 of GAD65 that was recognized solely by autoantibodies
      from patients with SPS but not by serum from type 1 diabetes patients. A mAb (N
      GAD65 mAb) recognizing this N-terminal epitope was successfully humanized to
      enhance its potential therapeutic value by reducing its overall immunogenicity.

PMID- 16301687
TI  - In vivo correction of complement regulatory protein deficiency with an inhibitor
      targeting the red blood cell membrane.
AB  - Because of the complement system's involvement in many human diseases and
      potential complications associated with its systemic blockade, site-specific
      regulation of this effector system is an attractive concept. We report on further
      developments of such an approach using a single-chain Ab fragment as a vehicle to
      deliver complement regulatory proteins to a defined cell type. In a model system
      in which RBCs deficient in complement receptor 1-related gene/protein y (Crry)
      are rapidly cleared after injection into wild-type animals by a complement
      dependent mechanism, we selectively reconstituted these cells with N- and C
      terminally targeted recombinant forms of Crry. Transfusion of Crry-coated
      knockout RBCs into C57BL/6 mice extended their in vivo half-life from <5 min to
      approximately 2 days. Maintenance of protective levels of Crry (by a combined
      treatment of donor and recipient RBCs) led to nearly normal RBC survival. Uniform
      in vitro and in vivo coating of the RBCs and the more efficient complement
      inhibitory capacity of C-terminally tagged Crry were other interesting features
      of this experimental system. These results suggest the possibility of using the
      single-chain Ab fragment-mediated targeting concept of complement regulatory
      proteins to restrict complement inhibition to the site of its excessive
      activation.

PMID- 16301688
TI  - Clinical practice guidelines and conflict of interest.

PMID- 16301689
TI  - All provinces likely to join tobacco litigation.

PMID- 16301690
TI  - National wait time standards remain elusive.

PMID- 16301691
TI  - Quebec's official numbers: 409 C. difficile deaths.

PMID- 16301692
TI  - Pandemic preparedness: begin at the source.

PMID- 16301694
TI  - Medicine by media: did a critical television documentary affect the prescribing
      of cyproterone--estradiol (Diane-35)?

PMID- 16301695
TI  - The use of provisionally licensed international medical graduates in Canada.

PMID- 16301696
TI  - Dermatologic emergencies.

PMID- 16301697
TI  - Legionella infection.

PMID- 16301698
TI  - Renal failure and ascites after remote laparoscopy.

PMID- 16301699
TI  - Is the timing of infant cereal introduction a risk factor for celiac disease
      autoimmunity?

PMID- 16301700
TI  - Measuring the severity of depression and remission in primary care: validation of
      the HAMD-7 scale.
AB  - BACKGROUND: Symptomatic remission is the optimal outcome in depression. A brief,
      validated tool for symptom measurement that can indicate when remission has
      occurred in mental health and primary care settings is unavailable. We evaluated
      a 7-item abbreviated version (HAMD-7) of the 17-item Hamilton Depression Rating
      Scale (HAMD-17) in a randomized controlled clinical trial of patients with major
      depressive disorder being cared for in primary care settings. METHODS: We
      enrolled 454 patients across 47 primary care settings who met DSM-IV-TR criteria
      for a major depressive disorder. Of these, 410 patients requiring antidepressant
      medication were randomized to have their symptoms rated with either HAMD-7 (n =
      205) or HAMD-17 (n = 205) as the primary measurement tool. The primary outcome
      was the proportion of patients who achieved a-priori defined responses to 8 weeks
      of therapy using each instrument. RESULTS: Of the 205 participants per group, 67%
      of those evaluated with HAMD-7 were classified as having responded to therapy
      (defined as a > or = 50% reduction from the pretreatment score), compared with
      74% of those evaluated with HAMD-17 (p = 0.43). The difference between the
      groups' changes in scores from baseline (pretreatment) to endpoint was
      significant (p < 0.001), without a main effect of group (p = 0.84) or group-by
      time (p = 0.83) interaction. The HAMD-7 test was brief to administer (e.g., 3-4
      min for 85% of the primary care physicians evaluated), which facilitated the
      efficient and structured evaluation of salient depressive symptoms.
      INTERPRETATION: The abbreviated HAMD-7 depression scale is equivalent to the HAMD
      17 in assessing remission in patients with a major depressive disorder undergoing
      drug therapy.

PMID- 16301701
TI  - When patients have to pay a share of drug costs: effects on frequency of
      physician visits, hospital admissions and filling of prescriptions.
AB  - BACKGROUND: Previous research has shown that patient cost-sharing leads to a
      reduction in overall health resource utilization. However, in Canada, where
      health care is provided free of charge except for prescription drugs, the
      converse may be true. We investigated the effect of prescription drug cost
      sharing on overall health care utilization among elderly patients with rheumatoid
      arthritis. METHODS: Elderly patients (> or = 65 years) were selected from a
      population-based cohort with rheumatoid arthritis. Those who had paid the maximum
      amount of dispensing fees (200 dollars) for the calendar year (from 1997 to 2000)
      were included in the analysis for that year. We defined the period during which
      the annual maximum co-payment had not been reached as the "cost-sharing period"
      and the one beyond which the annual maximum co-payment had been reached as the
      "free period." We compared health services utilization patterns between these
      periods during the 4 study years, including the number of hospital admissions,
      the number of physician visits, the number of prescriptions filled and the number
      of prescriptions per physician visit. RESULTS: Overall, 2968 elderly patients
      reached the annual maximum cost-sharing amount at least once during the study
      periods. Across the 4 years, there were 0.38 more physician visits per month (p <
      0.001), 0.50 fewer prescriptions filled per month (p = 0.001) and 0.52 fewer
      prescriptions filled per physician visit (p < 0.001) during the cost-sharing
      period than during the free period. Among patients who were admitted to the
      hospital at least once, there were 0.013 more admissions per month during the
      cost-sharing period than during the free period (p = 0.03). INTERPRETATION: In a
      predominantly publicly funded health care system, the implementation of cost
      containment policies such as prescription drug cost-sharing may have the
      unintended effect of increasing overall health utilization among elderly patients
      with rheumatoid arthritis.

PMID- 16301702
TI  - Prescription drug coverage: an essential service or a fringe benefit?

PMID- 16301703
TI  - Preventive care: so many recommendations, so little time.

PMID- 16301704
TI  - Short QT syndrome.
AB  - The QT interval on an electrocardiogram signifies the time required for the heart
      to repolarize after depolarization. It has long been appreciated that a long QT
      interval predisposes patients to life-threatening ventricular arrhythmia. Short
      QT syndrome is a newly described disease characterized by a shortened QT interval
      and by episodes of syncope, paroxysmal atrial fibrillation or life-threatening
      cardiac arrhythmias. The syndrome usually affects young and healthy people with
      no structural heart disease and may be present in sporadic cases as well as in
      families. Our understanding of a new disease has rarely benefitted so quickly
      from research in genetics, molecular biology and biophysics. It was first
      described in 2000 in a handful of patients, and since then 3 different genes
      associated with the disease and the biophysical basis have been described, and
      therapy has been made available. Here we review the current understanding of the
      pathophysiology, clinical presentation and treatment of short QT syndrome.

PMID- 16301705
TI  - A hypertensive snow bird.

PMID- 16301706
TI  - A hypertensive snow bird.

PMID- 16301707
TI  - Doctors and patients in the health care debate.

PMID- 16301708
TI  - Conforming to ICMJE principles.

PMID- 16301712
TI  - Vitamin B12 and homocysteine.

PMID- 16301714
TI  - Refresher on rubella.

PMID- 16301715
TI  - Vitamin B12 and homocysteine.

PMID- 16301716
TI  - Three- and 4-dimensional ultrasound in obstetrics and gynecology: proceedings of
      the American Institute of Ultrasound in Medicine Consensus Conference.
AB  - The American Institute of Ultrasound in Medicine convened a panel of physicians
      and scientists with interest and expertise in 3-dimensional (3D) ultrasound in
      obstetrics and gynecology to discuss the current diagnostic benefits and
      technical limitations in obstetrics and gynecology and consider the utility and
      role of this type of imaging in clinical practice now and in the future. This
      conference was held in Orlando, Florida, June 16 and 17, 2005. Discussions
      considered state-of-the-art applications of 3D ultrasound, specific clinical
      situations in which it has been found to be helpful, the role of 3D volume
      acquisition for improving diagnostic efficiency and patient throughput, and
      recommendations for future investigations related to the utility of volume
      sonography in obstetrics and gynecology.

PMID- 16301717
TI  - Three- and 4-dimensional ultrasound in obstetric practice: does it help?
AB  - OBJECTIVE: The purpose of this article was to review the published literature on
      3-dimensional ultrasound (3DUS) and 4-dimensional ultrasound (4DUS) in obstetrics
      and determine whether 3DUS adds diagnostic information to what is currently
      provided by 2-dimensional ultrasound (2DUS) and, if so, in what areas. METHODS: A
      PubMed search was conducted for articles reporting on the use of 3DUS or 4DUS in
      obstetrics. Seven-hundred six articles were identified, and among those, 525 were
      actually related to the subject of this review. Articles describing technical
      developments, clinical studies, reviews, editorials, and studies on fetal
      behavior or maternal-fetal bonding were reviewed. RESULTS: Three-dimensional
      ultrasound provides additional diagnostic information for the diagnosis of facial
      anomalies, especially facial clefts. There is also evidence that 3DUS provides
      additional diagnostic information in neural tube defects and skeletal
      malformations. Large studies comparing 2DUS and 3DUS for the diagnosis of
      congenital anomalies have not provided conclusive results. Preliminary evidence
      suggests that sonographic tomography may decrease the examination time of the
      obstetric ultrasound examination, with minimal impact on the visualization rates
      of anatomic structures. CONCLUSIONS: Three-dimensional ultrasound provides
      additional diagnostic information for the diagnosis of facial anomalies,
      evaluation of neural tube defects, and skeletal malformations. Additional
      research is needed to determine the clinical role of 3DUS and 4DUS for the
      diagnosis of congenital heart disease and central nervous system anomalies.
      Future studies should determine whether the information contained in the volume
      data set, by itself, is sufficient to evaluate fetal biometric measurements and
      diagnose congenital anomalies.

PMID- 16301718
TI  - Transitional cell carcinoma involving the distal ureter: assessment with
      transrectal and color Doppler ultrasonography.
AB  - OBJECTIVE: The purpose of this study was to compare the feasibility of
      transrectal ultrasonography (TRUS) and color Doppler ultrasonography (CDUS) with
      transabdominal ultrasonography (TAUS) for the diagnosis of transitional cell
      carcinoma (TCC) involving the distal ureter. METHODS: Our study group consisted
      of 12 patients having TCC involving the distal ureter who had undergone TAUS and
      TRUS. Verification of the TCC involving the distal ureter was made by surgery (n
      = 9) or urine cytologic examination combined with the imaging findings (n = 3).
      The gray scale images of TAUS and TRUS were retrospectively evaluated to
      determine whether the ureteral mass was visualized. The CDUS findings were
      compared with the T stage, the histopathologic grade, and the mean microvessel
      density of histopathologically proved distal ureteral TCCs (n = 8). RESULTS:
      Transabdominal ultrasonography showed hypoechoic ureteral dilatation in 6
      patients, a ureteral mass in 5, and anechoic ureteral dilatation in 1.
      Transrectal ultrasonography showed a ureteral mass in all 12 patients. Color
      Doppler ultrasonography could show blood flow in the ureteral mass in all
      patients. The tumor vascularity on CDUS showed no statistically significant
      relationship with the T stage, the histopathologic grade, and the mean
      microvessel density. CONCLUSIONS: Compared with TAUS, TRUS seems to improve the
      ability to detect TCC involving the distal ureter. In conjunction with TRUS, CDUS
      shows blood flow in the ureteral mass, and this may be helpful for the diagnosis
      of TCC involving the distal ureter.

PMID- 16301720
TI  - Value of Doppler sonography for predicting clinical outcome after renal artery
      revascularization in atherosclerotic renal artery stenosis.
AB  - OBJECTIVE: The purpose of this study was to prospectively evaluate the usefulness
      of Doppler sonography for predicting blood pressure and renal function
      improvement after percutaneous renal angioplasty in patients with unilateral
      atherosclerotic renal artery stenosis. METHODS: Thirty-six patients with
      successfully revascularized unilateral atherosclerotic renal artery stenosis were
      included. Patients were evaluated by Doppler sonography before treatment, with
      the resistive index (RI) and acceleration being measured in both kidneys. Blood
      pressure, number of antihypertensive drugs, and serum creatinine concentration
      were assessed before treatment and thereafter during a 23 +/- 15-month (mean +/-
      SD) period. RESULTS: In 20 of the 36 patients (55%), the RI was less than 0.80
      before revascularization. After treatment, blood pressure improved in 17 (85%) of
      those 20 patients and improved in 8 (50%) of 16 patients with an RI of greater
      than 0.80 (P < .05). Twenty-five patients had renal insufficiency pretreatment,
      and 11 (44%) had a baseline RI of less than 0.80. Improvement in renal function
      after angioplasty was shown in 5 (45%) of these 11 patients and in 4 (28.5%) of
      14 in the group with high RI (P > .05, not significant). On analysis of
      acceleration, blood pressure improved in 9 (69%) of 13 patients with acceleration
      of greater than 3 m/s(2) and in 16 (69.5%) of 23 with acceleration of less than 3
      m/s(2) (P > .05). In patients with renal insufficiency, 5 (50%) of 10 cases with
      normal baseline acceleration and 4 (27%) of 15 with low acceleration showed
      improvement in renal function (P > .05). CONCLUSIONS: An elevated RI should not
      exclude patients from a revascularization procedure because, although renal RI
      does correlate with blood pressure response to revascularization, it is not a
      useful parameter in predicting renal function outcome. Acceleration has no
      prognostic value.

PMID- 16301719
TI  - Contrast-enhanced ultrasonography in the diagnosis of solid renal tumors.
AB  - OBJECTIVE: The purpose of this study was to evaluate the usefulness of contrast
      enhanced ultrasonography (CEUS) in the diagnosis of solid renal tumors. METHODS:
      Twenty-nine patients with solid tumors detected on gray scale ultrasonography
      underwent resection for suspected renal malignancy. Findings of arterial phase
      contrast computed tomography (CT) and CEUS were compared for each diagnosis.
      RESULTS: Histopathologic examination of resected lesions showed malignancy in 26
      patients (clear cell carcinoma, n = 18; papillary renal cell carcinoma, n = 6;
      collecting duct carcinoma, n = 1; and infiltrative urothelial carcinoma, n = 1)
      and benign tumors in 3 patients (oncocytoma, n = 2; and angiomyolipoma, n = 1).
      Contrast CT failed to show tumor blood flow in 5 of 29 patients, whereas CEUS
      showed this in all patients. Positive predictive values of CEUS and contrast CT
      in the diagnosis of renal malignancy were 100% and 82.8%, respectively. Among
      clear cell carcinomas, hypervascularity was observed on contrast CT in 16 of 18
      patients and on CEUS in 17 of 18 patients. On the basis of hypervascularity,
      diagnostic sensitivity values for clear cell carcinoma were 94.4% for CEUS and
      88.9% for contrast CT, whereas specificity values were 45.5% for CEUS and 72.7%
      for contrast CT. Among papillary cell carcinomas, contrast CT showed avascular
      lesions in 4 of 6 patients. However, CEUS showed blood flow in these lesions,
      leading to diagnosis of hypovascular renal tumors. CONCLUSIONS: Contrast-enhanced
      ultrasonography was more sensitive for detecting slight tumor blood flow than
      contrast CT and was useful in preoperatively diagnosing malignant hypovascular
      renal tumors but was less so for hypervascular renal tumors.

PMID- 16301721
TI  - Is fluid ingestion really necessary during ultrasonography for detecting ureteral
      stones? A prospective randomized study.
AB  - OBJECTIVE: Ultrasonographic evaluation of ureteral stones is usually performed
      after fluid ingestion for filling the bladder to visualize the ureterovesical
      junction better. We hypothesized that water ingestion may decrease the imaging
      quality of ultrasonography for detecting ureter stones. In our prospective
      randomized study, the accuracy of ultrasonography for detecting ureteral stones
      performed with or without fluid intake were evaluated. METHODS: The study
      population comprised 150 consecutive patients thought to have ureteral stones who
      underwent ultrasonography. Patients were divided into 2 groups. Group A patients
      ingested 500 mL of water to distend the bladder before ultrasonographic
      examination. Group B patients were restricted from drinking any water at least 4
      hours before the procedure. RESULTS: Ultrasonography showed 35 (67.30%) of 52
      stones in group A and 68 (93.15%) of 73 stones in group B. The difference of
      detection rates between the 2 groups was statistically significant (P < .001).
      The greatest improvement in detection rates was noted in the middle ureter
      stones. The evaluated sensitivity and specificity rates for group A were 67% and
      82%, respectively, and those for group B were 93% and 94%. When the 2 methods
      were compared, total accuracy of ultrasonography increased from 71% in group A to
      93% in group B. CONCLUSIONS: This prospective randomized study showed that the
      diagnostic accuracy of ultrasonography for detection of middle ureteral stones
      increased significantly when performed without any water ingestion before the
      procedure. We recommend that patients thought to have ureteral stones should be
      first examined without any fluid ingestion.

PMID- 16301722
TI  - Follow-up of the transrectal ultrasonographic features of the prostate after
      biopsy: does any ultrasonographically detectable lesion form secondary to the
      first biopsy?
AB  - OBJECTIVE: The purpose of this study was to evaluate the transrectal
      ultrasonographic features of the prostate after biopsy and to find out whether
      any ultrasonographically detectable lesion forms secondary to biopsy. METHODS:
      Prebiopsy transrectal ultrasonographic findings in 60 consecutive patients who
      underwent repeated biopsies were evaluated. Detected lesions that were not
      defined before the first biopsy were considered postbiopsy-formed lesions and
      were sampled during the second biopsy. All transrectal ultrasonographically
      detected lesions were correlated with histopathologic results in the same
      locations. RESULTS: There were 7 (11.6%) patients with new hypoechoic lesions
      formed after the first biopsy. Histopathologic analysis of postbiopsy-detected
      lesions showed that 38.5% were cancer; 62.5% of the detected benign lesions were
      prostatitis foci. CONCLUSIONS: Prostate biopsy does not give rise to formation of
      fibrotic scar tissue in the peripheral zone. Most postbiopsy-detected lesions are
      prostatitis foci, but all hypoechoic lesions must be sampled during repeated
      prostate biopsies because of the 38.5% cancer detection rate.

PMID- 16301723
TI  - Acoustic output as measured by mechanical and thermal indices during routine
      obstetric ultrasound examinations.
AB  - OBJECTIVE: The purpose of this study was to quantify the acoustic output of
      clinical ultrasound instruments, as expressed by the thermal index (TI) and
      mechanical index (MI), during routine obstetric examinations. METHODS: A
      prospective, observational study was conducted. Sonographers were unaware of the
      data being sought. Data were collected regarding duration of the examination and
      specific duration spent at each MI and TI. RESULTS: A total of 11 first
      trimester, 14 second-trimester, and 12 third-trimester examinations were
      evaluated. The mean duration of the first-trimester examination was 8.9 minutes.
      The mean MI was 0.73 (range, 0.3-1.3), and the mean TI was 0.34 (0.1-1.7). The
      mean duration of the second-trimester examination was 31.8 minutes. The mean MI
      was 1.04 (0.5-1.5), and the mean TI was 0.28 (0.1-2.4). The mean duration of the
      third-trimester examination was 16.3 minutes. The mean MI was 1.06 (0.2-1.5), and
      the mean TI was 0.32 (0.1-2.4). Statistical significance existed across
      trimesters with regard to examination durations and MI (P < .001). However, no
      statistical significance existed in the TI across trimesters. During the third
      trimester, 3.5% of the examinations had a TI of greater than 1.0. Of these, 2.4%
      were between 1.0 and 1.49 and 1.1% were greater than 1.5. These changes (of TI >
      or = 1) were brief (mean +/- SD, 0.17 +/- 0.08 minutes) and were observed during
      the short periods of color Doppler imaging. CONCLUSIONS: Output levels during
      routine obstetric ultrasound examinations, as expressed by the MI and TI, are
      generally low. However, higher output levels, particularly TI levels of greater
      than 1.5, can be achieved, although they account for only a very small proportion
      of examination time.

PMID- 16301724
TI  - Intraoperative sonography for neurosurgery.
AB  - OBJECTIVE: The purpose of this study was to review the technical aspects and the
      clinical applications of intraoperative sonography of the central nervous system
      (CNS) as well as the characteristic appearances of brain and spine diseases.
      METHODS: A pictorial review of cases is presented on the basis of the performance
      and interpretation of intraoperative sonography of the CNS from January 1998 to
      December 2004 at a single academic institution. RESULTS: This technique is most
      commonly used for the localization and characterization of intracranial and
      spinal masses. Indications for intraoperative sonography of the CNS are biopsy
      guidance, tumor resection, and drainage or removal of inflammatory masses. It
      provides important additional information to the surgeon at the time of the
      operation and contributes to intraoperative decision making and surgical
      planning. This article reviews the advantages and limitations of intraoperative
      sonography of the CNS and highlights the typical appearance of CNS diseases.
      CONCLUSIONS: Intraoperative sonography of the CNS is an interactive technique and
      helps the neurosurgeon in decision making and surgical planning.

PMID- 16301725
TI  - Tomographic ultrasound imaging of the fetal heart: a new technique for
      identifying normal and abnormal cardiac anatomy.
AB  - OBJECTIVE: In 2003 and 2004, the American College of Radiology, the American
      Institute of Ultrasound in Medicine, and the American College of Obstetricians
      and Gynecologists published guidelines for the standard ultrasound examination of
      the fetus. Each group recommended that the outflow tracts of the fetal heart be
      examined if technically feasible. One method to accomplish this task is to
      perform a free-hand sweep of the transducer beam directed in a transverse plane
      from the 4-chamber view to the fetal neck. One problem with this approach is that
      the examiner may not direct the beam transversely and, therefore, may not
      accurately identify the outflow tract anatomy. METHODS: A new technology,
      tomographic ultrasound imaging (TUI), allows the examiner to obtain a volume data
      set that simultaneously displays multiple images at specific distances from the 4
      chamber view. This study examined TUI technology for identifying normal and
      abnormal fetal cardiac anatomy with the use of either static or spatiotemporal
      image correlation volume data sets. RESULTS: The 4 views used in the screening
      examination of the outflow tracts of the fetal heart (4-chamber, 5-chamber, 3
      vessel, and tracheal views) could be identified with the use of TUI technology in
      fetuses between 13 and 40 weeks' gestation. Examples of fetuses with abnormal
      cardiac anatomy of the outflow tracts (tetralogy of Fallot, transposition of the
      great vessels, and pulmonary stenosis) all showed abnormal anatomy on TUI.
      CONCLUSIONS: Tomographic ultrasound imaging technology enables the fetal examiner
      to evaluate the 4-chamber view and the outflow tracts in a systematic manner to
      identify normal and abnormal cardiac anatomy.

PMID- 16301726
TI  - Magnetic resonance imaging of the kinked fetal brain stem: a sign of severe
      dysgenesis.
AB  - OBJECTIVE: Magnetic resonance imaging (MRI) allows visualization of the fetal
      brain stem in a manner not previously possible. A "kinked" brain stem is a sign
      of severe neurodysgenesis. The purpose of this series was to describe cases of a
      kinked brain stem detected on prenatal MRI and to discuss the possible genetic
      and syndromic etiologies. METHODS: Seven cases of a kinked brain stem on fetal
      MRI (gestational age range, 18-34 weeks) were reviewed and correlated with other
      clinical, genetic, imaging, and autopsy findings. RESULTS: In all cases, there
      was associated cerebellar hypogenesis. Additional findings were ventriculomegaly
      (4 cases), cerebral hypogenesis (3 cases), microcephaly (4 cases), schizencephaly
      (1 case), cephalocele (1 case), hypogenesis of the corpus callosum (1 case), and
      hydrocephalus (1 case). In 2 cases, prenatal sonography misidentified the kinked
      brain stem as the cerebellum. CONCLUSIONS: A kinked brain stem is an indicator of
      severe neurodysgenesis arising early in gestation. Magnetic resonance imaging
      provides the necessary resolution to detect this sign and delineate any
      associated anomalies in utero to assist with further genetic evaluation,
      management, and counseling.

PMID- 16301727
TI  - Intratesticular varicocele: gray scale and color Doppler sonographic appearance.
AB  - OBJECTIVE: The purpose of this study was to evaluate the gray scale and color
      Doppler appearances of intratesticular varicocele (ITV) in a relatively large
      series of men and to compare the findings with those previously reported.
      METHODS: Fifteen ITVs found in 12 men referred for sonographic examination of a
      variety of scrotal conditions were retrospectively evaluated. Review of the side,
      location, shape, and diameter of the dilated veins, the presence of an
      extratesticular varicocele (ETV), and the color Doppler appearance of the ITV
      before and during the Valsalva maneuver was performed. RESULTS: Seven (47%) of 15
      ITVs were located in the left testis, 2 (13%) in the right, and 3 (20%)
      bilateral. Eighty-six percent of the ITVs were associated with an ipsilateral
      ETV. The locations of the ITVs were subcapsular in 60% of the cases and within or
      near the mediastinum of the testis in 40%. The shapes of the ITVs were tubular in
      46%, oval in 27%, and both tubular and oval in the remaining 27%. Color Doppler
      imaging showed spontaneous flow in 60% of cases, whereas in the remaining 40%,
      the blood flow could be seen only after the Valsalva maneuver. CONCLUSIONS:
      Intratesticular varicocele is a rare condition with a variable clinical and
      sonographic appearance. It is usually associated with ETV. It occurs in the left,
      right, or both testes and may be subcapsular or mediastinal in location. The
      prevalence of a subcapsular location of ITVs in this series was by far higher
      than previously mentioned in the literature. The Valsalva maneuver plays a very
      important role in the diagnosis of ITV because in almost half of cases, the flow
      will not show up spontaneously.

PMID- 16301728
TI  - Testicular adrenal rest tumors in a patient with congenital adrenal hyperplasia:
      sonographic and magnetic resonance imaging findings.

PMID- 16301729
TI  - Plasmacytoma of the testis.

PMID- 16301730
TI  - Fragile x syndrome associated with testicular microlithiasis in siblings.

PMID- 16301731
TI  - Vesical hirudiniasis: an unusual cause of bleeding from the urethra.

PMID- 16301732
TI  - Prenatal diagnosis of marshall syndrome by targeted sonography.

PMID- 16301733
TI  - Endometrial and subendometrial vascularity measurements in patients with
      intramural uterine fibroids * reply.

PMID- 16301734
TI  - Monoamniotic twin pregnancy discordant for body stalk anomaly: case report with
      nosologic implications.

PMID- 16301735
TI  - Fetal escape from the amniotic sac: follow-up from first trimester to delivery.

PMID- 16301736
TI  - The new obstetric ultrasound guidelines: some concerns.

PMID- 16301737
TI  - Eicosapentaenoic acid (20:5 n-3) increases fatty acid and glucose uptake in
      cultured human skeletal muscle cells.
AB  - This study was conducted to evaluate the chronic effects of eicosapentaenoic acid
      (EPA) on fatty acid and glucose metabolism in human skeletal muscle cells. Uptake
      of [14C]oleate was increased >2-fold after preincubation of myotubes with 0.6 mM
      EPA for 24 h, and incorporation into various lipid classes showed that cellular
      triacylgycerol (TAG) and phospholipids were increased 2- to 3-fold compared with
      control cells. After exposure to oleic acid (OA), TAG was increased 2-fold.
      Insulin (100 nM) further increased the incorporation of [14C]oleate into all
      lipid classes for EPA-treated myotubes. Fatty acid beta-oxidation was unchanged,
      and complete oxidation (CO2) decreased in EPA-treated cells. Basal glucose
      transport and oxidation (CO2) were increased 2-fold after EPA, and insulin (100
      nM) stimulated glucose transport and oxidation similarly in control and EPA
      treated myotubes, whereas these responses to insulin were abolished after OA
      treatment. Lower concentrations of EPA (0.1 mM) also increased fatty acid and
      glucose uptake. CD36/FAT (fatty acid transporter) mRNA expression was increased
      after EPA and OA treatment compared with control cells. Moreover, GLUT1
      expression was increased 2.5-fold by EPA, whereas GLUT4 expression was unchanged,
      and activities of the mitogen-activated protein kinase p38 and extracellular
      signal-regulated kinase were decreased after treatment with OA compared with EPA.
      Together, our data show that chronic exposure of myotubes to EPA promotes
      increased uptake and oxidation of glucose despite a markedly increased fatty acid
      uptake and synthesis of complex lipids.

PMID- 16301738
TI  - Measurement of stable isotopic enrichment and concentration of long-chain fatty
      acyl-carnitines in tissue by HPLC-MS.
AB  - We have developed a new method for the simultaneous measurements of stable
      isotopic tracer enrichments and concentrations of individual long-chain fatty
      acyl-carnitines in muscle tissue using ion-pairing high-performance liquid
      chromatography-electrospray ionization quadrupole mass spectrometry in the
      selected ion monitoring (SIM) mode. Long-chain fatty acyl-carnitines were
      extracted from frozen muscle tissue samples by acetonitrile/methanol. Baseline
      separation was achieved by reverse-phase HPLC in the presence of the volatile ion
      pairing reagent heptafluorobutyric acid. The SIM capability of a single
      quadrupole mass analyzer allows further separation of the ions of interest from
      the sample matrixes, providing very clean total and selected ion chromatograms
      that can be used to calculate the stable isotopic tracer enrichment and
      concentration of long-chain fatty acyl-carnitines in a single analysis. The
      combination of these two separation techniques greatly simplifies the sample
      preparation procedure and increases the detection sensitivity. Applying this
      protocol to biological muscle samples proves it to be a very sensitive, accurate,
      and precise analytical tool.

PMID- 16301739
TI  - How Heidelberger and Avery sweetened immunology.
AB  - In 1923, a young chemist-turned-microbiologist and his mentor made the startling
      discovery that bacterial sugars could be targeted by the immune system--a
      groundbreaking finding that helped launch the field of immunochemistry.

PMID- 16301740
TI  - Humanized mice: are we there yet?
AB  - Animal models have been instrumental in increasing the understanding of human
      physiology, particularly immunity. However, these animal models have been limited
      by practical considerations and genetic diversity. The creation of humanized mice
      that carry partial or complete human physiological systems may help overcome
      these obstacles. The National Institute of Allergy and Infectious Diseases
      convened a workshop on humanized mouse models for immunity in Bethesda, MD, on
      June 13-14, 2005, during which researchers discussed the benefits and limitations
      of existing animal models and offered insights into the development of future
      humanized mouse models.

PMID- 16301741
TI  - Schistosoma mansoni secretes a chemokine binding protein with antiinflammatory
      activity.
AB  - The coevolution of humans and infectious agents has exerted selective pressure on
      the immune system to control potentially lethal infections. Correspondingly,
      pathogens have evolved with various strategies to modulate and circumvent the
      host's innate and adaptive immune response. Schistosoma species are helminth
      parasites with genes that have been selected to modulate the host to tolerate
      chronic worm infections, often for decades, without overt morbidity. The
      modulation of immunity by schistosomes has been shown to prevent a range of
      immune-mediated diseases, including allergies and autoimmunity. Individual immune
      modulating schistosome molecules have, therefore, therapeutic potential as
      selective manipulators of the immune system to prevent unrelated diseases. Here
      we show that S. mansoni eggs secrete a protein into host tissues that binds
      certain chemokines and inhibits their interaction with host chemokine receptors
      and their biological activity. The purified recombinant S. mansoni chemokine
      binding protein (smCKBP) suppressed inflammation in several disease models.
      smCKBP is unrelated to host proteins and is the first described chemokine binding
      protein encoded by a pathogenic human parasite and may have potential as an
      antiinflammatory agent.

PMID- 16301742
TI  - Yersinia virulence factor YopJ acts as a deubiquitinase to inhibit NF-kappa B
      activation.
AB  - The bacterial pathogens of the genus Yersinia, the causative agents of plague,
      septicemia, and gastrointestinal syndromes, use a type III secretion system to
      inject virulence factors into host target cells. One virulence factor, YopJ, is
      essential for the death of infected macrophages and can block host
      proinflammatory responses by inhibiting both the nuclear factor kappaB (NF
      kappaB) and mitogen-activated protein kinase pathways, which might be important
      for evasion of the host immune response and aid in establishing a systemic
      infection. Here, we show that YopJ is a promiscuous deubiquitinating enzyme that
      negatively regulates signaling by removing ubiquitin moieties from critical
      proteins, such as TRAF2, TRAF6, and IkappaBalpha. In contrast to the
      cylindromatosis tumor suppressor CYLD, which attenuates NF-kappaB signaling by
      selectively removing K63-linked polyubiquitin chains that activate IkappaB
      kinase, YopJ also cleaves K48-linked chains and thereby inhibits proteasomal
      degradation of IkappaBalpha. YopJ, but not a catalytically inactive YopJ mutant,
      promoted deubiquitination of cellular proteins and cleaved both K48- and K63
      linked polyubiquitin. Moreover, an in vitro assay was established to demonstrate
      directly the deubiquitinating activity of purified YopJ.

PMID- 16301743
TI  - Toll-like receptor-independent gene induction program activated by mammalian DNA
      escaped from apoptotic DNA degradation.
AB  - Deoxyribonuclease (DNase) II in macrophages cleaves the DNA of engulfed apoptotic
      cells and of nuclei expelled from erythroid precursor cells. DNase II-deficient
      mouse embryos accumulate undigested DNA in macrophages, and die in feto because
      of the activation of the interferon beta (IFNbeta) gene. Here, we found that the
      F4/80-positive macrophages in DNase II(-/-) fetal liver specifically produce a
      set of cytokines such as IFNbeta, TNFalpha, and CXCL10. Whereas, IFN-inducible
      genes (2'5'-oligo(A) synthetase, IRF7, and ISG15) were expressed not only in
      macrophages but also in other F4/80-negative cells. When DNase II(-/-)
      macrophages or embryonal fibroblasts engulfed apoptotic cells, they expressed the
      IFNbeta and CXCL10 genes. The ablation of Toll-like receptor (TLR) 3 and 9, or
      their adaptor molecules (MyD88 and TRIF), had no effect on the lethality of the
      DNase II(-/-) mice. These results indicate that there is a TLR-independent
      sensing mechanism to activate the innate immunity for the endogenous DNA escaping
      lysosomal degradation.

PMID- 16301745
TI  - Where CD4+CD25+ T reg cells impinge on autoimmune diabetes.
AB  - Foxp3 is required for the generation and activity of CD4(+)CD25(+) regulatory T
      (T reg) cells, which are important controllers of autoimmunity, including type-1
      diabetes. To determine where T reg cells affect the diabetogenic cascade, we
      crossed the Foxp3 scurfy mutation, which eliminates T reg cells, with the BDC2.5
      T cell receptor (TCR) transgenic mouse line. In this model, the absence of T reg
      cells did not augment the initial activation or phenotypic characteristics of
      effector T cells in the draining lymph nodes, nor accelerate the onset of T cell
      infiltration of the pancreatic islets. However, this insulitis was immediately
      destructive, causing a dramatic progression to overt diabetes. Microarray
      analysis revealed that T reg cells in the insulitic lesion adopted a gene
      expression program different from that in lymph nodes, whereas T reg cells in
      draining or irrelevant lymph nodes appeared very similar. Thus, T reg cells
      primarily impinge on autoimmune diabetes by reining in destructive T cells inside
      the islets, more than during the initial activation in the draining lymph nodes.

PMID- 16301744
TI  - BAFF regulates B cell survival by downregulating the BH3-only family member Bim
      via the ERK pathway.
AB  - The B cell activating factor belonging to the tumor necrosis factor family (BAFF)
      is required for B cell survival and maturation. The mechanisms by which BAFF
      mediates B cell survival are less understood. We found that BAFF and a
      proliferation-inducing ligand (APRIL), which are related, block B cell antigen
      receptor (BCR)-induced apoptosis upstream of mitochondrial damage, which is
      consistent with a role for Bcl-2 family proteins. BCR ligation strongly increased
      expression of the proapoptotic Bcl-2 homology 3-only Bcl-2 protein Bim in both
      WEHI-231 and splenic B cells, and increases in Bim were reversed by BAFF or
      APRIL. Small interfering RNA vector-mediated suppression of Bim blocked BCR
      induced apoptosis. BAFF also induced Bim phosphorylation and inhibited BCR
      induced association of Bim with Bcl-2. BAFF induced delayed but sustained
      stimulation of extracellular signal-regulated kinase (ERK) and its activators,
      mitogen-activated protein kinase/ERK activating kinase (MEK) and c-Raf, and MEK
      inhibitors promoted accumulation and dephosphorylation of Bim. These results
      suggest that BAFF inhibits BCR-induced death by down-regulating Bim via sustained
      ERK activation, demonstrating that BAFF directly regulates Bim function. Although
      transitional immature type 1 (T1) B cell numbers are normal in Bim(-/-) mice, T2
      and follicular mature B cells are elevated and marginal zone B cells are reduced.
      Our results suggest that mature B cell homeostasis is maintained by BAFF-mediated
      regulation of Bim.

PMID- 16301746
TI  - PU.1 is not strictly required for B cell development and its absence induces a B
      2 to B-1 cell switch.
AB  - In this paper, we describe the unexpected outgrowth of B lineage cells from PU.1(
      /-) fetal liver cultures. The cells express all early B cell genes tested,
      including the putative PU.1 target genes IL-7R and EBF but not B220, and can
      produce immunoglobulin M. However, we observed a delay in the PU.1(-/-) B cell
      outgrowth and reduced precursor frequencies, indicating that although PU.1 is not
      strictly required for B cell commitment, it facilitates B cell development. We
      also ablated PU.1 in CD19-expressing B lineage cells in vivo, using a Cre-lox
      approach that allows them to be tracked. PU.1 excision resulted in a shift from B
      2 cells to B-1-like cells, which dramatically increased with the age of the mice.
      Our data indicate that this shift is predominantly caused by a B-2 to B-1 cell
      reprogramming. Furthermore, we found that B-2 cells express substantially more
      PU.1 than B-1 cells, which is consistent with the idea that maintenance of the B
      2 cell phenotype requires relatively high levels of PU.1, but B-1 cells require
      little.

PMID- 16301747
TI  - PKC beta regulates BCR-mediated IKK activation by facilitating the interaction
      between TAK1 and CARMA1.
AB  - The B cell antigen receptor (BCR)-mediated activation of IkappaB kinase (IKK) and
      nuclear factor-kappaB require protein kinase C (PKC)beta; however, the mechanism
      by which PKCbeta regulates IKK is unclear. Here, we demonstrate that another
      protein kinase, TGFbeta-activated kinase (TAK)1, is essential for IKK activation
      in response to BCR stimulation. TAK1 interacts with the phosphorylated CARMA1
      (also known as caspase recruitment domain [CARD]11, Bimp3) and this interaction
      is mediated by PKCbeta. IKK is also recruited to the CARMA1-Bcl10-mucosal
      associated lymphoid tissue 1 adaptor complex in a PKCbeta-dependent manner.
      Hence, our data suggest that phosphorylation of CARMA1, mediated by PKCbeta,
      brings two key protein kinases, TAK1 and IKK, into close proximity, thereby
      allowing TAK1 to phosphorylate IKK.

PMID- 16301749
TI  - The very 5' end and the constant region of Ig genes are spared from somatic
      mutation because AID does not access these regions.
AB  - Somatic hypermutation (SHM) is restricted to VDJ regions and their adjacent
      flanks in immunoglobulin (Ig) genes, whereas constant regions are spared.
      Mutations occur after about 100 nucleotides downstream of the promoter and extend
      to 1-2 kb. We have asked why the very 5' and most of the 3' region of Ig genes
      are unmutated. Does the activation-induced cytosine deaminase (AID) that
      initiates SHM not gain access to these regions, or does AID gain access, but the
      resulting uracils are repaired error-free because error-prone repair does not
      gain access? The distribution of mutations was compared between uracil DNA
      glycosylase (Ung)-deficient and wild-type mice in endogenous Ig genes and in an
      Ig transgene. If AID gains access to the 5' and 3' regions that are unmutated in
      wild-type mice, one would expect an "AID footprint," namely transition mutations
      from C and G in Ung-deficient mice in the regions normally devoid of SHM. We find
      that the distribution of total mutations and transitions from C and G is
      indistinguishable in wild-type and Ung-deficient mice. Thus, AID does not gain
      access to the 5' and constant regions of Ig genes. The implications for the role
      of transcription and Ung in SHM are discussed.

PMID- 16301750
TI  - Reliability and validity of the Outcome Expectations for Exercise Scale-2.
AB  - Development of a reliable and valid measure of outcome expectations for exercise
      for older adults will help establish the relationship between outcome
      expectations and exercise and facilitate the development of interventions to
      increase physical activity in older adults. The purpose of this study was to test
      the reliability and validity of the Outcome Expectations for Exercise-2 Scale
      (OEE-2), a 13-item measure with two subscales: positive OEE (POEE) and negative
      OEE (NOEE). The OEE-2 scale was given to 161 residents in a continuing-care
      retirement community. There was some evidence of validity based on confirmatory
      factor analysis, Rasch-analysis INFIT and OUTFIT statistics, and convergent
      validity and test criterion relationships. There was some evidence for
      reliability of the OEE-2 based on alpha coefficients, person- and item-separation
      reliability indexes, and R(2)values. Based on analyses, suggested revisions are
      provided for future use of the OEE-2. Although ongoing reliability and validity
      testing are needed, the OEE-2 scale can be used to identify older adults with low
      outcome expectations for exercise, and interventions can then be implemented to
      strengthen these expectations and improve exercise behavior.

PMID- 16301748
TI  - Selective accumulation of differentiated CD8+ T cells specific for respiratory
      viruses in the human lung.
AB  - The lungs are frequently challenged by viruses, and resident CD8(+) T cells
      likely contribute to the surveillance of these pathogens. To obtain insight into
      local T cell immunity to respiratory viruses in humans, we determined the
      specificity, phenotype, and function of lung-residing CD8(+) T cells and
      peripheral blood CD8(+) T cells in a paired analysis. The lung contained markedly
      higher frequencies of influenza (FLU)-specific and respiratory syncytial virus
      (RSV)-specific CD8(+) T cells when compared with the circulation. This contrasted
      with an equal distribution of cytomegalovirus- and Epstein-Bar virus-specific
      CD8(+) T cells. Noticeably, a substantial fraction of the lung-residing FLU- and
      RSV-specific CD8(+) T cells had progressed to a relatively late differentiation
      phenotype, reflected by low expression of CD28 and CD27. Lung-derived FLU
      specific CD8(+) T cells had low activation requirements, as expansion of these
      cells could be initiated by cognate peptide in the absence of helper cell-derived
      signals. Thus, the human lung contains high numbers of differentiated FLU- and
      RSV-specific memory CD8(+) T cells that can readily expand upon reexposure to
      virus. Resident lung T cells may provide immediate immunological protection
      against pulmonary virus infections.

PMID- 16301751
TI  - Development of a lateral mobility task to identify individuals at risk for
      mobility disability and functional decline.
AB  - Lateral mobility is integral to many activities of daily living involving
      transfer from one position to another. The objective of this study was to develop
      and evaluate the validity and test-retest reliability of a lateral-mobility
      (LATMOB) task for older adults. Measurements of lateral mobility, balance, and
      strength and self-reported and performance-based physical functioning were
      obtained in 63 women and 77 men > or = 50 years of age. The LATMOB task was
      significantly correlated with age, knee-extensor strength, grip strength,
      functional reach, and one-leg-stance time. Test-retest reliability of the task
      was excellent. The LATMOB task was highly correlated with the car task. Balance
      was significantly correlated with time to get into and out of a car and
      performance on the LATMOB task. The LATMOB task was significantly correlated with
      the Short Physical Performance Battery score. The LATMOB task is valid and
      reliable, but additional work is needed to assess its sensitivity to change and
      predictive validity.

PMID- 16301752
TI  - Force steadiness in the lower extremities as an independent predictor of
      functional performance in older women.
AB  - The relationship between isometric force control and functional performance is
      unknown. Submaximal steadiness and accuracy were measured during a constant force
      matching task at 50% of maximal isometric voluntary contraction (MVC) of the knee
      extensors in 19 older women (70-89 years). Other variables included MVC, rate of
      torque development, and EMG activity. Functional performance was assessed during
      maximal performance of walking endurance, chair rising, and stair climbing.
      Isometric steadiness (but not accuracy) was found to independently predict chair
      rise time and stair-climbing power and explained more variance in these tasks
      than any other variable. Walking endurance was related to muscle strength but not
      steadiness. These results suggest that steadiness is an independent predictor of
      brief, stressful functional-performance tasks in older women with mild functional
      impairment. Thus, improving steadiness might help reduce functional limitations
      or disability in older adults.

PMID- 16301753
TI  - Dropout from exercise programs for seniors: a prospective cohort study.
AB  - This study examines dropout incidence, moment of dropout, and switching behavior
      in organized exercise programs for seniors in the Netherlands, as determined in a
      prospective cohort study (with baseline measurements at the start of the exercise
      program and follow-up after 6 months; N = 1,725, response rate 73%). Participants
      were community-living individuals 50+ who participated in different forms of
      organized exercise programs. The average dropout incidence was 0.15 per 6 months,
      which is lower than that for the general population. The dropout incidence and
      the timing of dropout differed substantially between the exercise programs. In
      total, 31% of people who dropped out of one type of exercise program switched to
      another type of exercise. The type of program and exercise had a strong effect on
      differences in this switching behavior. It is recommended that switching behavior
      be monitored in future studies.

PMID- 16301754
TI  - Misconceptions about strength exercise among older adults.
AB  - The purposes of this study were to determine current opinions of strength
      exercise among older adults and whether knowledge of recommended protocols
      differs between strength-exercise participants and nonparticipants. One hundred
      twenty-nine older adults (77.5 +/- 8.6 years) responded to questions about their
      opinions, experiences, and knowledge of strength-exercise recommendations. Some
      misconceptions were identified in the sample, with 48.4% of participants
      responding "no" to "strength training increases muscle mass," 45% responding "no"
      to "increasing weight is more important than number of repetitions for building
      strength," and 37% responding that walking is more effective than lifting weights
      at building muscle strength. The number of correct responses was related to the
      number of years in school (semipartial r(2)= .046). More education is needed
      about the benefits and recommendations to ensure proper use of current strength
      exercise protocols among older adults.

PMID- 16301755
TI  - Chronic osteoarthritis and adherence to exercise: a review of the literature.
AB  - Osteoarthritis (OA) is a chronic disease that disables many aging adults. People
      with OA are often asked to adhere to prescribed exercise regimens that must be
      undertaken in the presence of pain and other disease-related symptoms. We
      conducted a review of literature that focused on what is known about exercise
      adherence and the factors that influence exercise adherence among people with OA.
      Results revealed multiple determinants of exercise adherence; however, these
      determinants have not been carefully studied in the context of exercise adherence
      and OA. Almost all studies of exercise adherence among people with OA are short
      term and do not use validated measures of adherence. Moreover, poor adherence is
      the most compelling explanation for the declining impact of the benefits of
      exercise over time. We conclude that interventions to enhance self-efficacy,
      social support, and skills in long-term monitoring of progress are necessary to
      foster exercise adherence among people with OA.

PMID- 16301756
TI  - Suitability of physical activity questionnaires for older adults in fall
      prevention trials: a systematic review.
AB  - The purpose of the study was to identify physical activity questionnaires for
      older adults that might be suitable outcome measures in clinical trials of fall
      injury-prevention intervention and to undertake a systematic quality assessment
      of their measurement properties. PubMed, CINAHL, and PsycINFO were systematically
      searched to identify measurements and articles reporting the methodological
      quality of relevant measures. Quality extraction relating to content, population,
      reliability, validity, responsiveness, acceptability, practicality, and
      feasibility was undertaken. Twelve outcome measures met the inclusion criteria.
      There is limited evidence about the measures' properties. None of the measures is
      entirely satisfactory for use in a large-scale trial at present. There is a need
      to develop suitable measures. The Stanford 7-day Physical Activity Recall
      Questionnaire and the Community Health Activities Model Program for Seniors
      questionnaire might be appropriate for further development. The results have
      implications for the designs of large-scale trials investigating many different
      geriatric syndromes.

PMID- 16301757
TI  - Reverse epidemiology of blood pressure in dialysis patients: implications for
      treatment?

PMID- 16301758
TI  - Reverse epidemiology: paradoxical observations in haemodialysis patients.
AB  - Traditional risk factors, such as high blood pressure (BP), obesity and
      hypercholesterolaemia, play an important role in the development of
      cardiovascular disease (CVD), not only in the general population but also in
      patients with chronic renal disease. In recent years, it has become less clear
      whether these conventional risk factors are responsible for the extremely high
      risk of CVD in chronic haemodialysis (CHD) patients. Recent studies have shown
      that low BP, body mass index (BMI) and serum cholesterol are often correlated
      with an unfavourable clinical outcome. Thus, whereas traditional risk factors of
      CVD are correlated with an unfavourable outcome in the general population and
      patients with chronic renal failure not yet on dialysis, in CHD patients these
      factors appear to be protective and associated with an improved survival.
      Therefore, these phenomena have been referred to as 'paradoxical or reverse
      epidemiology'. The aetiology of this inverse relationship is not clear.
      Interestingly, in CHD patients, both C-reactive protein, a marker of
      inflammation, and (pre)albumin, a marker of nutrition, are important independent
      predictors of mortality. It has been speculated that what is known as the
      malnutritioninflammation-atherosclerosis complex underlies, at least partly, the
      phenomenon of reverse epidemiology, since malnutrition causes a low BMI and
      hypocholesterolaemia. Hence, besides care for adequate nutrition, attempts should
      be made to reduce inflammation. In this respect, various haemodialysis-related
      factors, such as the purity of the dialysate and several characteristics of the
      dialyser, deserve attention.

PMID- 16301759
TI  - Cytokines and biotrauma in ventilator-induced lung injury: a critical review of
      the literature.
AB  - BACKGROUND: Mechanical ventilation is known to induce and aggravate lung injury.
      One of the underlying mechanisms is biotrauma, an inflammatory response in which
      cytokines play a crucial role. OBJECTIVE: To review the literature on the role of
      cytokines in ventilator-induced lung injury (VILI) and multiple organ dysfunction
      syndrome (MODS). MATERIAL AND METHODS: 57 English written, peer-reviewed articles
      on cytokines in in-vitro settings (n=5), ex-vivo models (n=9) in-vitro models
      (n=19) and clinical trials (n=24). RESULTS: Mechanical ventilation (MV) can
      induce cytokine upregulation in both healthy and injured lungs. The underlying
      mechanisms include alveolar cellular responses to stretch with subsequent
      decompartimentalisation due to concomitant cellular barrier damage. The cytokines
      involved are interleukin (IL)-8 and CXC chemokines, and probably IL-6, IL-1beta
      and tumour necrosis factor (TNF)-alpha. Cytokines are important for signalling
      between inflammatory cells and recruiting leucocytes to the lung. There is strong
      circumstantial evidence that the release of cytokines into the systemic
      circulation contributes to the pathogenesis of MODS. Multiple studies demonstrate
      the relation between elevated proinflammatory cytokine concentrations and
      mortality. CONCLUSION: Cytokines are likely to play a role in the various
      interrelated processes that lead to VILI and other MV-related complications, such
      as MODS and possibly ventilatorassociated pneumonia. Cytokines are good surrogate
      endpoints in exploring the pathogenesis and pathophysiology of VILI in both
      experimental and clinical studies.

PMID- 16301760
TI  - Idiopathic focal segmental glomerulosclerosis: a favourable prognosis in
      untreated patients?
AB  - BACKGROUND: Patients with focal segmental glomerulosclerosis (FSGS) are
      considered to have a poor prognosis and spontaneous remissions are seldom
      reported. However, FSGS is not a single disease entity. Our aim was to describe
      the clinical course in initially untreated patients with recently diagnosed
      idiopathic FSGS. METHODS: This was a retrospective study of patients with a
      diagnosis of FSGS by histology, who fulfilled the following criteria: proteinuria
      >3.5 g/day, normal renal function, duration of proteinuria or hypertension of
      less than one year, normal-sized kidneys, no underlying renal disease, and a
      negative family history. Renal biopsies were reviewed without knowledge of the
      clinical course. RESULTS: Twenty patients (13 male, 7 female) fulfilled the study
      criteria. Median age was 49.3 (range 21.8 to 73.0) years, serum creatinine 90 +/-
      20 micromol/l, proteinuria 10.0 +/- 5.5 g/day and serum albumin 24 +/- 6 g/l.
      After a median follow-up of 9.4 (2.1-18.6) years, 13 patients (65%) were in
      remission of proteinuria. Renal function deterioration occurred in seven
      patients, and prompted treatment in four of them. The ten-year death-censored
      renal survival was 89%. Renal function deterioration and remission rate could be
      predicted by selectivity index, serum albumin at three months after renal biopsy
      and the percentage of glomeruli with segmental sclerosis. CONCLUSION: Focal
      glomerulosclerosis is not a single disease. Case definition using strict clinical
      criteria identifies a subgroup of patients with idiopathic FSGS who have a good
      prognosis. In the majority of these patients immunosuppressive therapy is not
      warranted.

PMID- 16301761
TI  - Long-term blood pressure monitoring and echocardiographic findings in patients
      with end-stage renal disease: reverse epidemiology explained?
AB  - BACKGROUND: In patients with end-stage renal disease (ESRD) hypertension is
      common and often leads to left ventricular (LV) hypertrophy and diastolic
      dysfunction, but hypotension at the onset of dialysis is associated with
      increased mortality. We studied blood pressure data over longer periods of time
      in patients on haemodialysis and related them to echocardiographic outcome, in
      order to elucidate these contradictory findings. METHODS: In 50 haemodialysis
      patients mean arterial pressure (MAP) and pulse pressure (PP) were calculated in
      the first three months of haemodialysis, the complete period from the start of
      haemodialysis until echocardiography and the last three months of haemodialysis
      before echocardiography. Hypertension load, pulse pressure and interdialytic
      weight gain were quantified and related to echocardiography. RESULTS: LV mass
      index was associated with MAP in all three periods, and also with the
      hypertension load, PP and PP load. In patients with LV dilatation, MAP and PP
      averaged over the complete period of dialysis were 5 to 7 mmHg higher than in
      patients without LV dilatation. Blood pressure parameters were the same in
      patients with or without LV diastolic dysfunction or systolic dysfunction.
      Systolic dysfunction was more frequent in patients undergoing long-term
      haemodialysis treatment. Interdialytic weight gain was not associated with any of
      the echocardiographic variables. CONCLUSION: When long-term blood pressure values
      are considered, hypertension is associated with parameters of early cardiac
      damage such as increased LV mass index and not with parameters of advanced heart
      failure such as systolic dysfunction. This supports the hypothesis that the
      presence of advanced heart failure reciprocally influences blood pressure in a
      negative way, thereby explaining the 'reverse epidemiology' of blood pressure and
      mortality in ESRD.

PMID- 16301762
TI  - Mediastinal mass.

PMID- 16301763
TI  - Initial cytomegalovirus prophylaxis with ganciclovir: no guarantee for prevention
      of late serious manifestations of CMV after solid organ transplantation.
AB  - A 37-year-old woman presented with malaise, upper abdominal pain and fever seven
      months after renal transplantation. She was seronegative for cytomegalovirus
      (CMV) and had received a kidney from a seropositive donor. She had received CMV
      prophylaxis (oral ganciclovir) for three months after transplantation. During
      this period all tests for CMV remained negative. On admission, she presented with
      symptoms compatible with an acute abdomen and with deterioration of renal
      function. On emergency laparotomy a perforation of the ileum was found. The
      resected specimen showed an ulcer with vasculitis at the site of perforation,
      with both microscopic (owl's eye inclusion bodies), as well as
      immunohistochemical evidence for a CMV infection. CMV can reactivate (usually in
      the first three months) after transplantation, sometimes resulting in serious
      morbidity. The use of antiviral prophylaxis during and after transplantation has
      certainly decreased the number and severity of CMV infections. This case
      illustrates that life-threatening infections such as CMV can still emerge a long
      time after transplantation. Unrelenting awareness of this condition is mandatory,
      even after apparently adequate anti-CMV prophylaxis.

PMID- 16301764
TI  - Psoas abscess: report of a series and review of the literature.
AB  - We describe a series of twelve patients with a psoas abscess seen in a three-year
      period in a university hospital and a large teaching hospital in the Netherlands.
      In our series, five of the 12 patients had a primary psoas abscess. The
      predisposing conditions were intravenous drug use, diabetes mellitus, prostate
      carcinoma and haematoma in the psoas muscle in a patient with haemophilia A.
      Seven of the 12 patients had a secondary psoas abscess. Five cases were due to
      vertebral osteomyelitis including two cases of tuberculosis. In the other two
      cases it was due to colitis and urinary tract infection. It is remarkable that in
      our series there was only one patient with a psoas abscess secondary to a disease
      of the digestive tract, while this is the most common cause of a secondary psoas
      abscess in the literature. There were two cases of tuberculosis which is an
      emerging disease again.

PMID- 16301765
TI  - Healthons: errorless healthcare with bionic hugs and no need for quality control.
AB  - Errorless, invisible, continuous and infrastructure-free healthcare should become
      our goal. In order to achieve that goal, we need to rapidly move from current
      episodic and emergency-driven "healthcare delivery system" to an intelligent and
      extelligent health environment. That requires introduction of distributed
      affective Intelligent Caring Creatures (ICCs) consisting of healthons. Healthons
      are tools combining prevention with diagnosis and treatment based on continuous
      monitoring and analyzing of vital signs and biochemistry. Unlike humans, who
      posses only two or three dimensions of thinking, healthons can assure errorless
      health because of their adaptability, flexibility, and multidimensional reasoning
      capability. ICCs can do "the right thing" based on (1) state-of-art medical
      knowledge, (2) data about emotional, physiological, and genetic state of a
      consumer and (3) moral values of a consumer. The transition to the intelligent
      health environment based on ICCs requires the solutions to many currently
      unsolved healthcare problems. This paper lists the unsolved problems (by analogy
      to mathematical unsolved problems list) and explains why errorless healthcare
      with bionic hugs and no need for quality control is possible.

PMID- 16301766
TI  - The prospects for medical technology in the next decade.
AB  - Powerful forces encourage the growth of medical technology (health benefits,
      private equity capital, public funding, pervasive academic research, consumer
      demand, specialist training, reimbursement mechanisms, and industry competition).
      Countervailing forces that inhibit growth are the costs of the technology,
      difficulty in evaluating clinical and cost effectiveness, unequal patient access,
      and misuse, overuse, and underuse. While technology funding sources continue to
      expand, so do the methodologies for technology assessment. They are part of a
      broad movement to better manage the diffusion of medical technology. Specific
      proposals include more centralized planning, more discriminating federal funding,
      drug price controls, curtailing insurance reimbursements, more selective adoption
      of new technologies, and more rigorous attention to cost effectiveness. Savvy
      develops of and investors in new medical technology will anticipate these changes
      and take them into account in their planning.

PMID- 16301767
TI  - Innovation in telehealth and a role for the government.
AB  - The convergence of information technology and telecommunications, including
      Internet technologies, is emerging as a key tool to drive increased efficiency
      and effectiveness in health systems worldwide. With part of its roots in medical
      research for military and space applications, telemedicine is expected to make it
      possible to link medical expertise with patients in the most distant locations
      providing clinicians with valuable new tools for remote monitoring, diagnosis,
      and intervention.

PMID- 16301768
TI  - Present and future challenges in medical data management: economics, ethics, and
      the law.
AB  - Electronically-linked knowledge plays an increasingly central role in the
      delivery of health services worldwide. Medical data collection, archival, and
      analysis are all increasing in both rate and volume; large, cohesive collections
      of personal health information are emerging rapidly. Factors driving this
      integration include value-added methods of diagnosis and therapy, interest in
      evidence-based practices, safety concerns, and increased consumer demand for
      personalized, comprehensive medical services. Practitioners, businesses,
      patients, and the public at large would be well-served to develop and sustain a
      dialogue addressing these phenomena, including assessments their of economic,
      ethical, legal implications.

PMID- 16301769
TI  - Healthwear: medical technology becomes wearable.
AB  - Widespread adoption of sensors that monitor the wearer's vital signs and other
      indicators promises to improve care for the aged and chronically ill while
      amassing a database that can enhance treatment and reduce medical costs.

PMID- 16301770
TI  - Interfacing biology and computing for health: the future of home diagnostics.
AB  - Major advances in science and technology are converging to enable the development
      of a broad range of diagnostic aids for use in the home. These range from devices
      designed to diagnose infectious disease, to real-time continuous monitoring of
      endogenous biomarkers for cancer, cardiovascular health, and the like. This
      chapter briefly reviews some of the technical, biological, and social challenges
      associated with home diagnostic aids. In addition to providing several scenarios
      of how such devices might be used, we describe our own efforts in this area.

PMID- 16301771
TI  - Designing and Evaluating Home-Based, Just-in-Time Supportive Technology.
AB  - At MIT, a multi-disciplinary team of researchers is studying how to create
      pervasive computing environments for the home. We are developing technologies and
      design strategies that use context-aware sensing to empower people with
      information by presenting it at precisely the right time and place. Contrary to
      many visions of future home environments in the literature, we advocate an
      approach that uses technology to teach as opposed to using technology primarily
      for automated control. We have constructed a "living laboratory" that will
      provide a unique, flexible infrastructure for scientifically studying the power
      of pervasive computing for motivating learning and behavior change in the home.
      This facility, called the PlaceLab, is being used to study technology for
      creating homes that are supportive.

PMID- 16301772
TI  - Health. Care. Anywhere. Today.
AB  - What if clinical quality medical equipment were available to every consumer in a
      form factor that was inexpensive, accurate, and easy to use? What if this
      equipment provided information that previously was un-measurable or very
      difficult to measure? What if the physiological state of individuals, at
      resolutions measured in thousandths of a second instead of in visits per year,
      could be measured easily, making it possible to ascertain caloric intake and
      expenditure, patterns of sleep, contextual activities such as working-out and
      driving, even parameters of mental state and health. What aspect of healthcare
      would not change? We present a system that is available today that enables this
      vision. This award-winning multi-channel wearable physiological monitor has
      enabled the collection of more than 90 million minutes of data in natural
      settings from thousands of subjects engaged in diverse activities. Data modeling
      efforts are resulting in applications that present meaningful and actionable
      information in real-time to users and their designated collaborators (physicians,
      family members, counselors, coaches, etc.) We describe the SenseWear system, its
      design, and a summary of validation studies, current commercial applications, and
      ongoing research. This discussion will show how the convergence of design for
      wearability, advances in machine learning, and improvements in wireless
      technology will manifest the future of health care as personal, ubiquitous, and
      collaborative.

PMID- 16301773
TI  - How do we get the medical intelligence out?
AB  - Two factors are driving a new wave of medical products. The first is the use of
      technology to make products "intelligent"--that is, build them not only to
      measure a particular parameter, like blood glucose, but to help patients and
      caregivers manage conditions. This allows the users of these products focus less
      on the technical aspects of treating a condition (e.g. calculating the proper
      amount of insulin to treat a given level of blood glucose) and more on the
      overall management of the disease. The second development is the rapid movement
      of devices from the doctor's office to the home. Chain drug stores carry dozens
      of medical devices for home use by consumers. The challenge for manufacturers and
      designers is to present the medical device's intelligence in a way that is
      palatable to the consumer. One important theme is that medical product consumers
      are also consumers of everything else: home electronics, appliances, clothing,
      etc. These consumers are applying the same decision-making processes they use
      when buying a blender to the process of buying a medical device. It is therefore
      necessary for medical product manufacturers to create devices that interact with
      consumers in consumer-friendly ways. Putting intelligence into a product is one
      thing; helping the consumer utilize and appreciate it is quite another. This
      chapter covers some principles to keep in mind, and discusses a framework for
      better design of intelligent medical products that connect with consumers on
      emotional and functional levels beyond simple medical efficacy.

PMID- 16301774
TI  - Future of computer implant technology and intelligent human-machine systems.
AB  - Linking the human nervous system and brain directly to a computer opens up
      innumerable possibilities, not only in the future world of medicine, but also as
      a potential way of technically evolving all humans. This, however, presents
      something of an ethical problem. Nevertheless, the only way to actually find out
      what is realistically possible and what is not is to carry out practical
      experimentation using implant technology and to witness the results. This chapter
      describes the most recent self-experimentation trials carried out by the author
      and his team.

PMID- 16301775
TI  - Future of caring machines.
AB  - Feeling cared for has profound effects on physiology, cognition and emotional
      state, and has significant health ramifications whether the source of this
      feeling is an intimate other, friend or health provider. Unfortunately, not
      everyone has access to social networks populated with caring individuals or has
      health providers who are patient, empathic and reliably available when emotional
      support is needed. Over the last decade, a range of computational artifacts and
      technologies have been developed that could help fill this unmet need in many
      peoples' lives. Caring machines are technologies that interact with an individual
      to accomplish a goal while also behaving in ways that give the individual the
      feeling of being cared for. This chapter presents evidence that these machines
      can begin to lead to significant health benefits, such as increased adherence to
      prescribed health behavior change and medication regimens.

PMID- 16301776
TI  - Cyber-anthropology: a new study on human and technological co-evolution.
AB  - For the first time cyber-anthropology is defined as a concept and a new field of
      study aimed at the analysis of person's reciprocal relations with the computer
      generated (CG) world evolved as a result of technological progress. In the cyber
      era, simulated reality has come to the point of becoming a force that has the
      potential to transform the human race. Digital beings such as virtual and
      embodied agents, although not a part of the natural human habitat, have become
      necessary elements of people's surroundings and life conditions. As a theoretical
      construct, Cyber-anthropology is concerned with the merger of natural and
      artificial worlds mediated by the human imagination, as well as compatibility
      between people and digital life they have created. As an empirical study, Cyber
      anthropology deals with the psychophysiology and psychophysics, semantic and
      semiotics of human engagement with computer-generated reality that is viewed as a
      Complex Interactive System. Personal competence as a crucial element of any cyber
      system underlines the importance of psychological culture in artificial world
      exploration. A newly developed concept of Psychological Culture is viewed as an
      essential part of Cyber-anthropology while concentrating on the following core
      issues: (1) ethical questions, such as whether or not technological tools can be
      employed to solve human problems; (2) moral consequences of bringing cutting edge
      technology into our every day life; (3) studies of individual differences
      regarding psychological competence of technology users through effective vs.
      ineffective, independent vs. addictive, and active vs. passive dichotomies.
      Psychological Culture is defined as the study of a person's competence associated
      with the use of modern technology and individual acceptability of technological
      innovations. Several crucial dilemmas arise when a human being is engaged in a
      simulated environment, and artificial agents inhabit a human world. The ultimate
      goal of Psychological Culture is to provide people with the knowledge necessary
      for adequate recognition of scientific innovations to overcome obstacles in the
      process of implementing technology to enhance human well being.

PMID- 16301777
TI  - Harnessing the power of an intelligent health environment in cancer control.
AB  - In 1971, when Congress declared "war on cancer," the public's perception was
      driven by an image of a single cure for a single disease. What researchers have
      learned since that time is that cancer is a formidable enemy made up of more than
      100 different disease etiologies. The war on cancer became a war of the 21st
      century; a war to be fought on multiple fronts against a diffuse enemy and for
      which prevention was the most judicious path to victory. To fight this new war on
      cancer, the National Cancer Institute must seek to harness the power of health
      informatics to create a supportive environment for transforming science,
      delivering safe and patient-centric health care, and creating an environment of
      personal empowerment in public health. Three different types of health
      informatics applications are implicated: (a) applications in bioinformatics,
      which are intended to revitalize the engine of scientific discovery; (b)
      applications in medical informatics, which will create a safer and more effective
      environment for delivery; and (c) applications in consumer informatics, which
      will enable individuals to advance the charge of their own ongoing health care
      over the course of their lives. To keep these applications on track, health care
      administrators must take a sociotechnical approach to implementation. The new
      systems must be built into the health care environment in such a way that they
      support human capacities, provide failsafe backups in the face of cognitive and
      physical limitations, and support continuous quality improvement.

PMID- 16301778
TI  - Future of anti-addiction vaccines.
AB  - The medical rational for using anti-drug antibodies in the serum as a treatment
      is to reduce drug levels in the brain and to bind drug before it enters the
      brain. Drugs of abuse are small molecules that can readily cross the blood brain
      barrier, while antibodies are larger molecules that cannot get into the brain.
      Thus, any drug that is bound to antibody also cannot cross the blood brain
      barrier and cannot enter the brain. Active anti-drug vaccines stimulate the body
      to makes its own antibodies, but the small size of abused drugs prevents them
      from stimulating an immune response. Thus, individuals do not ordinarily produce
      antibodies to abused drugs, and vaccines to stimulate antibodies are made by
      chemically linking these abused drugs to toxins such as cholera toxin.
      Alternatively, passive immunotherapy uses monoclonal antibodies that are
      generated in a laboratory and then administered via intravenous injection.
      Antibodies can be used to treat drug overdose; to reduce drug use relapse; or to
      protect certain at risk populations who have not yet become drug dependent. The
      advantages of anti-addiction vaccines are that antibodies target the drug, not
      the drug's sites of action in the brain and antibody binding inactivates the
      drug. These vaccines can complement behavioral and other medical therapies with
      minimal side effects and are not addictive like some chemical agonists.
      Technology advances in manufacturing and delivery systems will improve future
      anti-addiction vaccines, but social acceptance of anti-addiction vaccines will
      depend on substance abuse program staff and the families of substance abusers,
      who have some values that oppose medical solutions to addictive diseases and view
      addictions as moral problems.

PMID- 16301779
TI  - Automating addiction treatment: enhancing the human experience and creating a fix
      for the future.
AB  - The country's system of providing treatment for people struggling with addiction
      requires a fundamental overhaul. To address these daunting problems, a group of
      experts from outside the addiction field met in an intensive retreat and
      envisioned a new future for addiction treatment that would use the latest
      available technology. Retreat leaders employed creative techniques to help free
      up thinking beyond incremental improvement ideas. Current and former addicts or
      alcoholics and family members also attended the retreat to provide the panelists
      with a real-world understanding of their lives. Through this process, the
      panelists generated eight idea categories that visualized future treatments for
      addiction using technology. They were: (1) Integrated System and Record; (2)
      Monitoring/Treatment; (3) Virtual Experiences; (4) Treatment Access and "One Stop
      Shop"; (5) Networks; (6) Tailored Media Campaigns; (7) Diagnostic Tools; and (8)
      Help for Family. Two stories illustrate how these ideas could help a heroin
      addict and an alcoholic. The sponsors plan another meeting to bring these
      visionary concepts closer to real application.

PMID- 16301780
TI  - A strategy for postponing aging indefinitely.
AB  - It may seem premature to be discussing approaches to the effective elimination of
      human aging as a cause of death at a time when essentially no progress has yet
      been made in even postponing it. However, two aspects of human aging combine to
      undermine this assessment. The first is that aging is happening to us throughout
      our lives but only results in appreciable functional decline after four or more
      decades of life: this shows that we can postpone aging arbitrarily well without
      knowing how to prevent it completely. The second is that the typical rate of
      refinement of dramatic technological breakthroughs is rather reliable (so long as
      public enthusiasm for them is abundant) and is fast enough to change such
      technologies (be they in medicine, transport, or computing) almost beyond
      recognition within a natural human lifespan. Here I explain, first, why it is
      reasonable to expect that (presuming adequate funding for the initial preclinical
      work) therapies that can add 30 healthy years to the remaining lifespan of
      healthy 55-year-olds will arrive within the next few decades, and, second, why
      those who benefit from those therapies will very probably continue to benefit
      from progressively improved therapies indefinitely and thus avoid debilitation or
      death from age-related causes at any age.

PMID- 16301781
TI  - Future of caring for an aging population: trends, technology, and caregiving.
AB  - Demographic trends clearly indicate that the US population aging patterns will
      continue to skew increasingly older for decades to come. Driven largely by
      healthcare and environmental improvements, the average life expectancy in the
      industrialized world has increased almost 30 years in the last century, allowing
      people to routinely live well into their 70s and beyond. A concomitant trend has
      also emerged as a result of increased longevity - the increased number of family
      caregivers responsible for managing the diverse needs of an elderly spouse or
      parent. This chapter reviews these emerging trends and their ramifications in
      more detail. It will also provide insights into some of the issues facing family
      caregivers as they attempt to balance this added responsibility along with other
      demands in their lives. Finally, this chapter will outline some of the technology
      driven, needs-based solutions that are necessary for maintaining the quality of
      life for both the family caregiver and the care recipient.

PMID- 16301782
TI  - Promoting safe and comfortable driving for elders.
AB  - Americans are life-long drivers. It is imperative that aging drivers remain on
      the road safely. This chapter addresses one strategy for achieving this end,
      namely the utilization of low-tech vehicle modifications for addressing
      challenges with driving due to functional deficits that normally occur with
      aging. It focuses primarily on the selection of useful features to be
      demonstrated in a video intervention in a research project to assess whether
      watching the video would increase elders' awareness of and likelihood of using
      the features. The features were chosen with the assistance of a panel of experts
      in transportation, aging, rehabilitation, and related fields plus a focus group
      of older drivers. Selecting the features, developing survey instruments, and
      producing the video constitute Phase I of the study. Phase II investigates
      whether watching a video would increase older drivers' awareness of such features
      and motivate them to use any of them. This chapter also includes an overview of
      Phase II and some comments with respect to high-tech features and the future of
      automobile travel.

PMID- 16301783
TI  - Global medicine technology.
AB  - In little more than a decade, linkages between health care technologies of
      different cultures and continents have merged, resulting in global medicine
      technology. The next generation of young scientists and clinicians from both the
      research and clinical communities are merging established ancient technologies
      from outside the U.S. with modern medical technology and forging new ground in an
      increasingly challenging health care climate. Presently researchers, clinicians
      and communities are active in finding ways of using global medical technology to
      attack our most difficult and chronic (therefore expensive) health care problems.
      Using recent inventions, such as the fMRI, researchers and clinicians are
      understanding how and why they work. This chapter briefly discusses key ideas in
      the movement towards global medical technology: healthcare culture, mind-brain
      body dialogue, and self-care including a self care exercise for the spine.

PMID- 16301784
TI  - Shaping a healthy future: megabyte, not mega bite!
AB  - The globalization of obesity is not a myth. Scientific and technologic advances
      have increased food production and availability while decreasing demand for
      physical activity. These developments, in turn, have contributed to peoples'
      cognitive and behavioral relationship with food selection and consumption. The
      more you see, the more you want. Although disparities in food distribution and
      personal economics still exist, the problem of over consumption is becoming
      widespread among low income groups in developed countries and among the high
      income in developing countries. The development of innovative technologies such
      as described in this chapter may help ebb the tide of obesity and improve the
      global future of health.

PMID- 16301785
TI  - Digital literacy in a landscape of data: a plea for a broader definition for
      citizens and patients.
AB  - The term 'digital literacy' is taking on a broader definition and greater
      urgency, as ubiquitous computing becomes a reality, and individuals and
      communities find their bodies and actions creating an exuberant wellspring of
      rich, complex data. These biological and sociological data can be ignored, used
      alone or shared with others for various reasons - for personal or social good or
      ill. Although strategies to protect our data from commercial, criminal, and
      governmental access are already being debated daily in the media, this paper is a
      brief plea for why we need to expand our concerns beyond the current financial
      and medical record security issues.

PMID- 16301786
TI  - Situated, strategic, and AI-Enhanced technology introduction to healthcare.
AB  - We work hard on creating AI-wings for physicians to let them fly higher and
      faster in diagnosing patients--a task that physicians do not want to automate.
      What we do not work hard on is determining the ENVIRONMENT in which physicians'
      AI wings are supposed to function. It seems to be a job for social/business
      analysts that have their own separate kingdom. For the sake of all of us
      (potential patients!) social/business consultants and their methodologies should
      not be treated as a separate kingdom. The most urgent task is to achieve synergy
      between (1) AI/Fuzzy/Neural research, (2) Applied medical AI, (3) Social/Business
      research on medical institutions. We need this synergy in order to assure
      humanistic medical technology; technology flexible and sensitive enough to
      facilitate healthcare work while leaving space for human pride and creativity. In
      order to achieve humanistic technology, designers should consider the impact of
      technological breakthroughs on the organizations in which this technology will
      function and the nature of work of humans destined to use this technology.
      Situated (different for each organization), Strategic (based on an in-depth
      knowledge of Healthcare business), and AI-Enhanced (ended with a dynamic model)
      method for introducing technology to Healthcare allows identifying areas where
      technology can make medical work easier. Using this method before automating
      human work will get us closer to the ideal where there is no discontinuity
      between design and use of programs; where the technology matches users' needs
      perfectly--the world with humanistic technology and healthcare workers with AI
      wings.

PMID- 16301787
TI  - Towards an intelligent hospital environment: OR of the future.
AB  - Patients, providers, payers, and government demand more effective and efficient
      healthcare services, and the healthcare industry needs innovative ways to re
      invent core processes. Business process reengineering (BPR) showed adopting new
      hospital information systems can leverage this transformation and workflow
      management technologies can automate process management. Our research indicates
      workflow technologies in healthcare require real time patient monitoring,
      detection of adverse events, and adaptive responses to breakdown in normal
      processes. Adaptive workflow systems are rarely implemented making current
      workflow implementations inappropriate for healthcare. The advent of evidence
      based medicine, guideline based practice, and better understanding of cognitive
      workflow combined with novel technologies including Radio Frequency
      Identification (RFID), mobile/wireless technologies, internet workflow,
      intelligent agents, and Service Oriented Architectures (SOA) opens up new and
      exciting ways of automating business processes. Total situational awareness of
      events, timing, and location of healthcare activities can generate self
      organizing change in behaviors of humans and machines. A test bed of a novel
      approach towards continuous process management was designed for the new Weinburg
      Surgery Building at the University of Maryland Medical. Early results based on
      clinical process mapping and analysis of patient flow bottlenecks demonstrated
      100% improvement in delivery of supplies and instruments at surgery start time.
      This work has been directly applied to the design of the DARPA Trauma Pod
      research program where robotic surgery will be performed on wounded soldiers on
      the battlefield.

PMID- 16301788
TI  - Framework for measuring adaptive knowledge-rich systems performance.
AB  - The universe is non repeatable in nature--most of events cannot be prestated and
      do not repeat themselves. The only way to create systems that are truly useful is
      to make them adaptive (able to reason by analogy and learn) and rich in knowledge
      (including common sense knowledge). Adaptive and knowledge-rich health management
      could get us closer to errorless health care where small incremental adjustments
      happen all the time preventing occurrence of an error. In the era of adaptive
      systems we need to have a way to evaluate their performance. Are they truly
      adaptive? How adaptive are they? Are they accurate enough? Are they fast enough?
      Are they cost effective? This chapter presents general framework for measuring
      adaptive knowledge-rich systems' performance and includes among others
      definitions of adaptiveness factor, britt (a unit of brittleness) and uso-quant
      (unit of usefulness of a piece of knowledge). Measuring adaptive knowledge-rich
      systems performance is one of the most important research areas that can have a
      big pay-off in healthcare now and in the future.

PMID- 16301789
TI  - Enhancing drop stability in protein crystallization by chemical patterning.
AB  - The motion of protein drops on crystallization media during routine handling is a
      major factor affecting the reproducibility of crystallization conditions. Drop
      stability can be enhanced by chemical patterning to more effectively pin the
      drop's contact line. As an example, a hydrophilic area is patterned on an
      initially flat hydrophobic glass slide. The drop remains confined to the
      hydrophilic area and the maximum drop size that remains stable when the slide is
      rotated to the vertical position increases. This simple method is readily
      scalable and has the potential to significantly improve the outcomes of hanging
      drop and sitting-drop crystallization.

PMID- 16301791
TI  - Non-steroidal anti-inflammatory drugs as potent inhibitors of phospholipase A2:
      structure of the complex of phospholipase A2 with niflumic acid at 2.5 Angstroms
      resolution.
AB  - Phospholipase A(2) (PLA(2); EC 3.1.3.4) catalyzes the first step of the
      production of proinflammatory compounds collectively known as eicosanoids. The
      binding of phospholipid substrates to PLA(2) occurs through a well formed
      hydrophobic channel. Surface plasmon resonance studies have shown that niflumic
      acid binds to Naja naja sagittifera PLA(2) with an affinity that corresponds to a
      dissociation constant (K(d)) of 4.3 x 10(-5) M. Binding studies of PLA(2) with
      niflumic acid were also carried out using a standard PLA(2) kit that gave an
      approximate binding constant, K(i), of 1.26 +/- 0.05 x 10(-6) M. Therefore, in
      order to establish the viability of PLA(2) as a potential target molecule for
      drug design against inflammation, arthritis and rheumatism, the three-dimensional
      structure of the complex of PLA(2) with the known anti-inflammatory agent
      niflumic acid [2-[3-(trifluoromethyl)anilino]nicotinic acid] has been determined
      at 2.5 Angstroms resolution. The structure of the complex has been refined to an
      R factor of 0.187. The structure determination reveals the presence of one
      niflumic acid molecule at the substrate-binding site of PLA(2). It shows that
      niflumic acid interacts with the important active-site residues His48 and Asp49
      through two water molecules. It is observed that the niflumic acid molecule is
      completely buried in the substrate-binding hydrophobic channel. The conformations
      of the binding site in PLA(2) as well as that of niflumic acid are not altered
      upon binding. However, the orientation of the side chain of Trp19, which is
      located at the entry of the substrate-binding site, has changed from that found
      in the native PLA(2), indicating its familiar role.

PMID- 16301792
TI  - Structure of a DNA duplex with all-AT base pairs.
AB  - The structure of the oligonucleotide duplex d(AAATATTT)(2) has been obtained in
      two crystal forms. In both cases the duplexes show Watson-Crick base pairs and
      are organized as a helical arrangement of stacked oligonucleotides. The helices
      contain either 11 duplexes in seven turns (form I) or 14 duplexes in nine turns
      (form II). As a result, the crystals have rather large unit cells. Such an
      organization of DNA duplexes has not been previously described in oligonucleotide
      crystal structures. The columns of stacked duplexes are organized in a
      pseudohexagonal arrangement. They do not show any direct lateral interactions;
      instead, these are indirectly mediated by shared and disordered hydrated ions.
      Such interactions are similar to those found in DNA fibres. The structural
      parameters of the individual base steps coincide with those found in other
      structures which contain CG terminal base pairs.

PMID- 16301790
TI  - Structure of murine angiogenin: features of the substrate- and cell-binding
      regions and prospects for inhibitor-binding studies.
AB  - Angiogenin is an unusual member of the pancreatic ribonuclease superfamily that
      induces blood-vessel formation and is a promising anticancer target. The three
      dimensional structure of murine angiogenin (mAng) has been determined by X-ray
      crystallography. Two structures are presented: one is a complex with sulfate ions
      (1.5 Angstroms resolution) and the other a complex with phosphate ions (1.6
      Angstroms resolution). Residues forming the putative B(1), P(1) and B(2) subsites
      occupy positions similar to their hAng counterparts and are likely to play
      similar roles. The anions occupy the P(1) subsite, sulfate binding conventionally
      and phosphate adopting two orientations, one of which is novel. The B(1) subsite
      is obstructed by Glu116 and Phe119, with the latter assuming a less invasive
      position than its hAng counterpart. Hydrophobic interactions between the C
      terminal segment and the main body of the protein are more extensive than in hAng
      and may underly the lower enzymatic activity of the murine protein. Elsewhere,
      the structure of the H3-B2 loop supports the view that hAng Asn61 interacts
      directly with cell-surface molecules and does not merely stabilize adjacent
      regions of the hAng structure. mAng crystals appear to offer small-molecule
      inhibitors a clear route to the active site and may even withstand a
      reorientation of the C-terminal segment that provides access to the cryptic B(1)
      subsite. These features represent considerable advantages over crystalline hAng
      and bAng.

PMID- 16301793
TI  - Anatomy of a trans-cis peptide transition during least-squares refinement of
      rubrerythrin.
AB  - A detailed view is presented of the effects of one round of 20 cycles of
      restrained least-squares refinement of rubreythrin in which a trans peptide
      between Gly78 and Ile79 converts to a cis conformation automatically. While the
      omega angle for the peptide changes by nearly 180 degrees , the maximum shift in
      any atomic position is 1.32 Angstroms. The peptide converts by passing through a
      non-ideal structure containing a nearly linear C-N-C(alpha) bond angle. The
      overall motion is not possible for real or virtual molecular models with ideal
      bond lengths, angles and torsion angles. Strengthening the stereochemical bond
      length and bond angle restraints halts the structural change.

PMID- 16301794
TI  - Conformational flexibility of Mycobacterium tuberculosis thioredoxin reductase:
      crystal structure and normal-mode analysis.
AB  - The thioredoxin system exists ubiquitously and participates in essential
      antioxidant and redox-regulation processes via a pair of conserved cysteine
      residues. In Mycobacterium tuberculosis, which lacks a genuine glutathione
      system, the thioredoxin system provides reducing equivalents inside the cell. The
      three-dimensional structure of thioredoxin reductase from M. tuberculosis has
      been determined at 3 A resolution. TLS refinement reveals a large libration axis,
      showing that NADPH-binding domain has large anisotropic disorder. The relative
      rotation of the NADPH domain with respect to the FAD domain is necessary for the
      thioredoxin reduction cycle, as it brings the spatially distant reacting sites
      close together. Normal-mode analysis carried out based on the elastic network
      model shows that the motion required to bring about the functional conformational
      change can be accounted for by motion along one single mode. TLS refinement and
      normal-mode analysis thus enhance our understanding of the associated
      conformational changes.

PMID- 16301795
TI  - High-throughput phase-diagram mapping via powder diffraction: a case study of
      HEWL versus pH.
AB  - 44 samples of tetragonal hen egg-white lysozyme (HEWL) were obtained as a series
      of polycrystalline precipitates at 277 K and room temperature in the pH range
      between 6.56 and 3.33. The precipitates were investigated by the collection of
      high-resolution powder X-ray diffraction data at 295 K, which reveal the
      tetragonal or orthorhombic forms of lysozyme depending on the temperature and pH
      of crystallization. The use of a new robotic sample changer greatly facilitated
      these measurements. LeBail analyses of the powder patterns display a
      characteristic behaviour for the pH dependence of the tetragonal unit-cell
      parameters of HEWL crystallized at both temperatures. More detailed analysis
      shows that molecular replacement can give a suitable starting point for
      structural refinements, illustrating that powder data can be sufficient for this
      approach. Pawley or Rietveld refinements that fit a single model to four data
      sets simultaneously from four samples crystallized at pH values across the range
      studied benefit from improved powder data quality via the anisotropic changes in
      the unit cell. The Rietveld analysis gave an average structural model with
      excellent goodness of fit and stereochemistry.

PMID- 16301796
TI  - Extending the resolution and phase-quality limits in automated model building
      with iterative refinement.
AB  - Previously, the direct use of prior phase information from a single-wavelength
      anomalous diffraction (SAD) experiment with a multivariate likelihood function
      applied to automated model building with iterative refinement has been proposed
      [Skubak et al. (2004), Acta Cryst. D60, 2196-2201]. In this approach, the
      anomalous information from the experimental data is used in refinement to derive
      phase information in a maximum-likelihood formalism and provided a more
      theoretically valid way of incorporating prior phase information compared with
      current approaches. In the present work, the SAD multivariate likelihood function
      that directly uses prior phase information is tested against currently used
      functions on many different SAD data sets which exhibit a wide range of
      resolution limits and anomalous signal. The results clearly show the importance
      of the more theoretically valid utilization of prior phase information: the SAD
      function extends the resolution and phase-quality limits needed for successful
      automated model building with iterative refinement. Indeed, the multivariate
      likelihood function reduces the overfitting in the refinement procedure and
      performs consistently better than the current refinement targets in terms of the
      quality of the models obtained and the number of residues built.

PMID- 16301797
TI  - Structure of aluminium-bound ovotransferrin at 2.15 Angstroms resolution.
AB  - Transferrin, well known as an iron-transport protein, can bind other metal ions,
      including toxic ones, and is considered to play an important role in the
      transportation of such metal ions. Here, a crystal structure of aluminium-bound
      transferrin is described for the first time. Colourless needle-shaped crystals of
      aluminium-bound ovotransferrin were obtained in PEG 400 solution. Structural
      determination was performed by molecular replacement using diferric (iron-bound)
      ovotransferrin as a model and the structural refinement was performed in the 50
      2.15 Angstroms resolution range. The overall organization of the aluminium-bound
      form is almost the same as the iron-bound form: the protein is folded into two
      homologous lobes (N- and C-lobes) with two domains; two metal-binding sites are
      located within the inter-domain clefts of each lobe. Four residues (one Asp, two
      Tyr and one His) and one bicarbonate anion were found to bind an aluminium ion in
      either lobe, as in the iron-bound form. The highly similar domain-closed
      structure of the Al(3+)-bound form may permit the binding of Al(3+)-bound
      transferrin to the transferrin receptor. An unusual interaction, the dilysine
      trigger, which facilitates iron release at low pH in the endosome, was also found
      in the Al(3+)-bound form. These findings support the participation of transferrin
      in the transport of Al(3+) ions in vivo.

PMID- 16301798
TI  - Three-dimensional model-free experimental error correction of protein crystal
      diffraction data with free-R test.
AB  - Experimental error correction and scaling is the last step in X-ray diffraction
      data processing. It is also critical in obtaining good-quality data. In this
      study, an algorithm is proposed to more generally and efficiently correct
      experimental error in X-ray crystal diffraction data. With this algorithm, the
      experimental error is represented by a symbolic three-dimensional function C(xi,
      eta, t) in the detecting space. Here, (xi, eta) are the coordinates of the
      diffraction spots on the image and t represents the data-collection time. While
      the theoretical form of C(xi, eta, t) is not known, it will be determined from
      the data through computer-aided analysis. The free R(merge) is introduced to
      check the validity of the solution. The three-dimensional symbolic function does
      not carry any assumptions and thus can generally account for experimental errors
      in various X-ray crystal diffraction experiments that are normally too
      complicated to be described by any fixed formula. Tests will be given to compare
      the results from different algorithms.

PMID- 16301799
TI  - Structure of Escherichia coli ribonucleotide reductase R2 in space group P6122.
AB  - A new crystal form of wild-type ribonucleotide reductase R2 from Escherichia coli
      was obtained. Crystals grow in space group P6(1)22 with one R2 monomer in the
      asymmetric unit. A twofold crystallographic symmetry axis generates the
      physiological dimeric form of R2. Co-crystallization with CoCl(2) or MnCl(2)
      results in full occupancy of the dinuclear metal site. The structure of the
      Mn(II)-loaded form was determined to 2.6 Angstroms resolution by molecular
      replacement. The crystallization conditions, backbone conformation, crystal
      packing interactions and metal centers are compared with those of previously
      determined crystal forms.

PMID- 16301800
TI  - The structure at 1.6 Angstroms resolution of the protein product of the At4g34215
      gene from Arabidopsis thaliana.
AB  - The crystal structure of the At4g34215 protein of Arabidopsis thaliana was
      determined by molecular replacement and refined to an R factor of 14.6% (R(free)
      = 18.3%) at 1.6 Angstroms resolution. The crystal structure confirms that
      At4g34215 belongs to the SGNH-hydrolase superfamily of enzymes. The catalytic
      triad of the enzyme comprises residues Ser31, His238 and Asp235. In this
      structure the catalytic serine residue was found to be covalently modified,
      possibly by phenylmethylsulfonyl fluoride. The structure also reveals a
      previously undescribed variation within the active site. The conserved asparagine
      from block III, which provides a hydrogen bond for an oxyanion hole in the SGNH
      hydrolase superfamily enzymes, is missing in At4g34215 and is functionally
      replaced by Gln30 from block I. This residue is positioned in a catalytically
      competent conformation by nearby residues, including Gln159, Gly160 and Glu161,
      which are fully conserved in the carbohydrate esterase family 6 enzymes.

PMID- 16301801
TI  - Tapping the Protein Data Bank for crystallization information.
AB  - A database application has been developed for the collection of crystallographic
      information. This database (the BDP) has been populated with the information
      found in the Protein Data Bank (PDB). The tool has been used to store
      crystallization data parsed out of the PDB and these data may be used to extend
      the crystallization information found in the Biological Macromolecule
      Crystallization Database (BMCD) and could be used to refine crystallization
      methodology. A standard is proposed for describing a crystallization experiment
      that will ease future crystallization data collations and analyses.

PMID- 16301802
TI  - Structure of BthA-I complexed with p-bromophenacyl bromide: possible correlations
      with lack of pharmacological activity.
AB  - The crystal structure of an acidic phospholipase A(2) isolated from Bothrops
      jararacussu venom (BthA-I) chemically modified with p-bromophenacyl bromide (BPB)
      has been determined at 1.85 Angstroms resolution. The catalytic, platelet
      aggregation inhibition, anticoagulant and hypotensive activities of BthA-I are
      abolished by ligand binding. Electron-density maps permitted unambiguous
      identification of inhibitor covalently bound to His48 in the substrate-binding
      cleft. The BthA-I-BPB complex contains three structural regions that are modified
      after inhibitor binding: the Ca(2+)-binding loop, beta-wing and C-terminal
      regions. Comparison of BthA-I-BPB with two other BPB-inhibited PLA(2) structures
      suggests that in the absence of Na(+) ions at the Ca(2+)-binding loop, this loop
      and other regions of the PLA(2)s undergo structural changes. The BthA-I-BPB
      structure reveals a novel oligomeric conformation. This conformation is more
      energetically and conformationally stable than the native structure and the
      abolition of pharmacological activities by the ligand may be related to the
      oligomeric structural changes. A residue of the ;pancreatic' loop (Lys69), which
      is usually attributed as providing the anticoagulant effect, is in the dimeric
      interface of BthA-I-BPB, leading to a new hypothesis regarding the abolition of
      this activity by BPB.

PMID- 16301803
TI  - Conceptions and first results on the electrocrystallization behaviour of
      ferritin.
AB  - The role of electrochemical processes on Fe and CdSO(4) in the crystallization of
      horse spleen ferritin has been investigated using the cyclic voltammetry
      technique. It was found that although both species exhibit important redox
      properties in the presence of an external applied potential, CdSO(4) played a
      leading role not only in the nucleation process but also in the growth behaviour
      and morphology of ferritin crystals.

PMID- 16301804
TI  - Lactobacillus acidophilus expressing recombinant K99 adhesive fimbriae has an
      inhibitory effect on adhesion of enterotoxigenic Escherichia coli.
AB  - The most common enteric colibacillosis in neonatal and newborns is caused by
      enterotoxigenic Escherichia coli(ETEC). Colonization of ETEC in the small
      intestine is associated with adhesions using fimbriae, which is known as a
      specific adhesion factor and provides highly specific means for anchoring and
      prerequisite for an infectious agent. In the present study we have engineered
      Lactobacillus acidophilus to produce recombinant K99 fimbriae, which is used for
      the colonization to the intestine of pigs. The expression of K99 fimbrial protein
      was confirmed using SDS-PAGE, immunoblot and agglutination analyses. To evaluate
      a function of the K99 fimbrial protein, inhibition and competition tests were
      performed on pre-screened intestinal brush border from pigs. The tests showed
      that recombinant L. acidophilus, not control L. acidophilus, had a significant
      inhibitory effect to and competition against K99+ E. coli in a dose dependent
      manner. In conclusion, we demonstrated that recombinant K99 fimbriae producing L.
      acidophilus was able to prevent E. coli binding to intestinal brush border.

PMID- 16301805
TI  - Gene cloning and characterization of four MATE family multidrug efflux pumps from
      Vibrio cholerae non-O1.
AB  - There are six putative genes for multidrug and toxic compound extrusion (MATE)
      family multidrug efflux pumps in the chromosome of Vibrio cholerae. We have so
      far analyzed two MATE family pumps in V. cholerae non-O1 NCTC4716. Here we cloned
      four remaining genes for putative MATE family efflux pumps by the PCR method from
      this microorganism and designated them as vcmB, vcmD, vcmH and vcmN. Each one of
      the four genes was introduced and expressed in the drug hypersusceptible host
      Escherichia coli KAM32 cells. We observed elevated MICs of multiple antimicrobial
      agents, such as fluoroquinolones, aminoglycosides, ethidium bromide and Hoechst
      33342 in the transformants. Energydependent efflux of substrate was observed with
      the transformed cells. We found that efflux activities of VcmB, VcmD and VcmH
      were Na+-dependent, but that of VcmN was Na+-independent. Thus, all six of the
      MATE family multidrug efflux pumps of V. cholerae non-O1 have been characterized.
      We also found that all six genes were expressed in cells of V. cholerae non-O1.

PMID- 16301806
TI  - Prospective surveillance of community-onset and healthcare-associated methicillin
      resistant Staphylococcus aureus isolated from a university-affiliated hospital in
      Japan.
AB  - We conducted a prospective comparative study of community-onset (CO) and
      healthcare-associated (HA) methicillin-resistant Staphylococcus aureus(MRSA)
      strains between 2000 and 2001 at Tokyo Women's Medical University Hospital (1,500
      beds) in Japan. Of the 172 consecutive MRSA isolates analyzed, 13 (8%) were
      categorized as CO-MRSA. The mean age of patients with CO-MRSA was significantly
      younger than that of patients with HA-MRSA. Most CO-MRSA strains were isolated
      from skin and more likely to be susceptible to erythromycin, clindamycin,
      tetracycline, levofloxacin, and spectinomycin compared to HA-MRSA isolates.
      Pulsed-field gel electrophoresis (PFGE) analysis, staphylococcal cassette
      chromosome mec(SCCmec) typing, and multi-locus sequence typing (MLST) revealed
      that CO-MRSA strains were divided into the following multi-clones: 3 clone A: II:
      ST5 (PFGE type: SCCmec type: MLST sequence type); 1 L: II: ST5; 1 H: IV: ST1; 1
      I: IV: ST81; 2 D: IV: ST8; 1 B: IV: ST89; 1 B: IV: ST379; and 3 B: IV: ST91. Of
      the 159 HAMRSA strains, 124 (78%) belonged to a single clone (PFGE clone A:
      SCCmec type II: tst and sec positive: coagulase type II: multi-drug resistance).
      Four CO-MRSA strains belonging to PFGE clone B: SCCmec type IV: MLST clonal
      complex 509 (ST89, 91, 379) had the exfoliative toxin B (etb) genes, but all CO
      MRSA and HA-MRSA strains did not possess the Panton-Valentine leukocidin (pvl)
      genes. These results demonstrate that multiple lineages of CO-MRSA have the
      potential for dissemination in the community in Japan.

PMID- 16301807
TI  - Characterization of M gene-deficient rabies virus with advantages of effective
      immunization and safety as a vaccine strain.
AB  - Matrix (M) protein of rabies virus is known to play an important role in assembly
      and budding of the progeny virus. We generated an M gene-deficient rabies virus,
      RC-HLDeltaM, using a reverse genetics system of rabies virus RC-HL strain to
      develop a novel type of vaccine. RC-HLDeltaM infection was confined within a
      single cell in mouse neuroblastoma cells. This deficient virus failed to generate
      the progeny virus in the cells. In contrast, RC-HLDeltaM propagated in BHK cells
      inductively expressing M protein. Suckling and adult mice inoculated
      intracerebrally with the parental RC-HL strain showed lethal infection and
      transient body weight loss, respectively, whereas both suckling and adult mice
      inoculated with RC-HLDeltaM showed no symptoms. The neutralizing antibody against
      rabies virus was successfully induced by intramuscular immunization with 10(5)
      focus-forming units of RC-HLDeltaM but not UV-inactivated RC-HL. Intranasal
      immunization with RC-HLDeltaM resulted in almost the same antibody titer to
      rabies virus as that in the case of immunization with live RC-HL strain. These
      findings indicate that RC-HLDeltaM is a candidate for a novel rabies vaccine that
      is safer and more effective than are current vaccines.

PMID- 16301808
TI  - Contribution of anaphylatoxins to allergic inflammation in human lungs.
AB  - The contribution of complement activation to allergic asthma remains
      controversial. In order to elucidate the role played by the complement split
      products, anaphylatoxins C3a and C5a, we evaluated their effects on production of
      cysteinyl-leukotrienes (cysLTs) by human lung fragments following an anaphylactic
      reaction. The lung tissues obtained from two patients with lung cancer showed
      C5aR-, C5L2R-, and C3aR-mRNA expression. When the chopped lung fragments
      passively sensitized with human IgE were incubated with anti-human IgE antibody,
      a significant amount of cysLTs was generated in comparison with the control
      (without anti-IgE antibody). The co-addition of human C5a at doses of 0.1 to 10
      ng/ml to the anti-IgE antibody potentiated cysLT production. The response was
      bell-shaped in distribution, significant, and peaked at a C5a concentration of 1
      ng/ml. The co-addition of human C3a up to 1,000 ng/ml seemed to increase cysLT
      production, but not to any significant extent. A novel C5a receptor complementary
      peptide, acetylated peptide A, dose-dependently inhibited cysLT production by the
      human lung fragments following the anaphylactic reaction in the presence of 1
      ng/ml C5a. However, this peptide did not inhibit cysLT production in the presence
      of 100 ng/ml C3a. It is suggested that the anaphylatoxin C5a potentiates cysLT
      production in human lung tissues and contributes to allergic inflammation in
      disorders such as asthma, thus acetylated peptide A may be useful for suppressing
      allergic inflammation in the lungs.

PMID- 16301809
TI  - Detection and quantification of four species of the genus Clostridium in infant
      feces.
AB  - To determine the composition of Clostridium in the feces of infants approximately
      30 days old, we have developed a detection and quantification method of
      Clostridium paraputrificum, Clostridium perfringens, Clostridium tertium, and
      Clostridium difficile by species-specific primers. C. perfringens and C.
      difficile were detected in four fecal samples from 22 infants (18.2%), whereas C.
      paraputrificum was detected in three samples (16.7%). C. tertium was detected in
      two samples (9.1%). Moreover, the occurrences of the four species in bottle-and
      mix-fed infants were relatively higher than in breast-fed infants (P< 0.05).
      Subsequently, positive samples detected by nested PCR (polymerase chain reaction)
      were subjected to realtime PCR. The results showed that the numbers of C.
      paraputrificum, C. perfringens, C. tertium, and C. difficile ranged from about
      1x10(5) to 3x10(7) cells/g wet feces.

PMID- 16301810
TI  - Effect of orally administered non-viable Lactobacillus cells on murine humoral
      immune responses.
AB  - BALB/c mice were immunized intraperitoneally with the food antigen ovalbumin
      (OVA) while they were fed with Lactobacillus GG heated killed cell preparation.
      The oral administration of Lactobacillus GG did not appear to modify the antigen
      augmented serum IgE in the tested mice but significantly augmented serum OVA
      specific IgG in the tested mice fed with a diet containing 0.1% Lactobacillus GG
      as the non-viable cell preparation (P< 0.05). The fecal OVA specific IgA of the
      tested mice fed with nonviable Lactobacillus GG cells was also significantly
      elevated (P< 0.05) compared to those from OVA immunized mice. The spleen cells of
      mice fed with non-viable Lactobacillus GG cells secreted more IL-6 (P< 0.01).
      These results suggest that the non-viable Lactobacillus GG can augment the
      systemic and mucosal immune responses in a host animal favoring secretory IgA but
      not IgE in an adjuvant-like manner.

PMID- 16301811
TI  - Gene cloning and properties of the RND-type multidrug efflux pumps MexPQ-OpmE and
      MexMN-OprM from Pseudomonas aeruginosa.
AB  - We cloned two operons for putative RND-type multidrug efflux pumps from
      Pseudomonas aeruginosa by a PCR method. We designated the genes in one operon
      mexPQ(-opmE) and in another operon mexMN. Introduction of the mexPQ-opmE into
      drug hypersensitive cells resulted in elevated MICs of macrolides,
      fluoroquinolones and some other drugs. Introduction of the mexMN into the
      hypersensitive cells possessing oprM, but not into cells not possessing oprM,
      resulted in elevated MICs of chloramphenicol and thiamphenicol. Thus, we conclude
      that MexPQ-OpmE and MexMN-OprM are functional multidrug efflux pumps when
      expressed in P. aeruginosa.

PMID- 16301812
TI  - Mycobacterial RNase E-associated proteins.
AB  - RNase E and its complex with other proteins ('degradosome') play an important
      role in RNA processing and decay in Escherichia coli and in many other bacteria.
      To identify the proteins which can potentially interact with this enzyme in
      mycobacteria, Mycobacterium tuberculosis H37Rv RNase E was cloned and expressed
      as a 6HisFLAG-tagged fusion protein. Analysis of the mycobacterial RNase E
      overexpressed and purified from M. bovis BCG revealed the presence of GroEL and
      two other copurified proteins, products of the Mb1721 (inorganic
      polyphosphate/ATP-NAD kinase) and Mb0825c (acetyltransferase) genes. Identical
      copies of these two genes can be found in M. tuberculosis H37Rv.

PMID- 16301813
TI  - Identification of an HLA-A24-restricted OY-TES-1 epitope recognized by cytotoxic
      T-cells.
AB  - OY-TES-1 was identified as a human homologue of the mouse, guinea pig, and pig
      proacrosin binding protein sp32 precursor. Differential expression levels of OY
      TES-1 mRNA between testis and other normal tissues, and its expression in cancers
      indicated that OY-TES-1 would be classified as a cancer/testis antigen and
      considered to be a candidate of target antigen for cancer immunotherapy. In this
      study, we showed identification of HLA-A24-binding OY-TES-1 peptide, TES(401-409)
      (KTPFVSPLL) recognized by CD8 T-cells. Purified CD8 T-cells from healthy donors
      stimulated in vitro with the peptide-pulsed autologous DC and PBMC produced
      IFNgamma in response to the peptide-pulsed PBMC and showed cytotoxicity against
      the peptide-pulsed autologous EBV-B specifically. Furthermore, cytotoxicity was
      also observed against an OY-TES-1 mRNA-expressing tumor line, LK79. The retention
      time of the fraction in HPLC of the acid eluate from LK79 cells that showed
      positive sensitization against autologous EBV-B cells in recognition by CD8 CTL
      was the same as that of the fraction of the TES(401-409) peptide itself,
      suggesting that the TES(401-409) was a naturally processed peptide on LK79.

PMID- 16301814
TI  - Band 3/complement-mediated recognition and removal of normally senescent and
      pathological human erythrocytes.
AB  - Band 3 modifications that normally occur during physiological red blood cell
      (RBC) senescence in humans, and occasionally in pathological conditions are
      described in the context of their role in enhancing RBC recognition and
      phagocytic removal. Band 3 modifications are mostly due to oxidative insults that
      gradually accumulate during the RBC lifespan or impact massively in a shorter
      time period in pathological conditions. The oxidative insults that impact on the
      RBC, the protective mechanisms that counteract those damages and the phenotypic
      modifications that accumulate during the RBC lifespan are described. It is shown
      how specific oxidative as well as non-oxidative band 3 modifications enhance RBC
      membrane affinity for normally circulating anti-band 3 antibodies, and how
      membrane-bound anti-band 3 antibodies bring about a limited complement activation
      and membrane deposition of complement C3 fragments. The partially covalent
      complexes between anti-band 3 antibodies and complement C3 fragments are very
      powerful opsonins readily recognized by the CR1 complement receptor on the
      phagocyte. Band 3 modifications typically encountered in old RBCs have
      crystallized to a number of band 3-centered models of RBC senescence. One of
      those band 3-centered models, the so-called 'band 3/complement RBC removal model'
      first put up by Lutz et al. is discussed in more detail. Finally, it is shown how
      the genetic deficiency of glucose-6-phosphate dehydrogenase (G6PD) plus fava bean
      consumption, and a widespread RBC parasitic disease, P. falciparum malaria, may
      lead to massive and rapid destruction of RBCs by a mechanism comparable to a
      dramatic, time-compressed enhancement of normal RBC senescence.

PMID- 16301815
TI  - Chloride channel inhibition prevents ROS-dependent apoptosis induced by ischemia
      reperfusion in mouse cardiomyocytes.
AB  - Apoptosis of cardiomyocytes following ischemia and reperfusion is of clinical
      importance. However, little is known about the mechanism by which it is induced.
      Recently, essential roles of a Cl- channel whose activity triggers the apoptotic
      volume decrease and of reactive oxygen species (ROS) in activation of this
      channel have been identified in mitochondrion-mediated apoptosis. Therefore, in
      this study, involvement of Cl- channels and ROS in apoptosis was studied in
      primary mouse cardiomyocyte cultures subjected to ischemia-reperfusion. Apoptotic
      cell death as measured by caspase-3 activation, chromatin condensation, DNA
      laddering, and cell viability reduction was observed tens of hours after
      reperfusion but never immediately after ischemia. A non-selective Cl-channel
      blocker (DIDS or NPPB) rescued cells from apoptotic death when applied during the
      reperfusion, but not ischemia, period. Another blocker relatively specific to the
      volume-sensitive outwardly rectifying (VSOR) Cl-channel (phloretin) was also
      effective in protecting ischemic cardiomyocytes from apoptosis induced by
      reperfusion. A profound increase in intracellular ROS was detected in
      cardiomyocytes during the reperfusion, but not ischemia, period. Scavengers for
      ROS, H2O2 and superoxide all inhibited apoptosis induced by ischemia-reperfusion.
      Thus, it is concluded that the mechanism by which cardiomyocyte apoptosis is
      induced by ischemia-reperfusion involves VSOR Cl- channel activity and
      intracellular ROS production.

PMID- 16301816
TI  - Potassium and sodium balance in U937 cells during apoptosis with and without cell
      shrinkage.
AB  - Staurosporine (STS) and etoposide (Eto) induced apoptosis of the human
      histiocytic lymphoma cells U937 were studied to determine the role of monovalent
      ions in apoptotic cell shrinkage. Cell shrinkage, defined as cell dehydration,
      was assayed by measurement of buoyant density of cells in continuous Percoll
      gradient. The K+ and Na+ content in cells of different density fractions was
      estimated by flame emission analysis. Apoptosis was evaluated by confocal
      microscopy and flow cytometry of acridine orange stained cells, by flow DNA
      cytometry and by effector caspase activity. Apoptosis of U937 cells induced by 1
      muM STS for 4 h was found to be paralleled by an increase in buoyant density
      indicating cell shrinkage. An increase in density was accompanied by a decrease
      in K+ content (from 1.1 to 0.78 mmol/g protein), which exceeded the increase in
      Na+ content (from 0.30 to 0.34 mmol/g) and resulted in a significant decrease of
      the total K+ and Na+ content (from 1.4 to 1.1 mmol/g). In contrast to STS, 50
      microM Eto for 4 h or 0.8-8 microM Eto for 18-24 h induced apoptosis without
      triggering cell shrinkage. During apoptosis of U937 cells induced by Eto the
      intracellular K(+)/Na+ ratio decreased like in the cells treated with STS, but
      the total K+ and Na+ content remained virtually the same due to a decrease in K+
      content being nearly the same as an increase in Na+ content. Apoptotic cell
      dehydration correlated with the shift of the total cellular K+ and Na+ content.
      There was no statistically significant decrease in K+ concentration per cell
      water during apoptosis induced by either Eto (by 13.5%) or STS (by 8%), whereas
      increase in Na+ concentration per cell water was statistically significant (by
      27% and 47%, respectively). The data show that apoptosis can occur without cell
      shrinkage-dehydration, that apoptosis with shrinkage is mostly due to a decrease
      in cellular K+ content, and that this decrease is not accompanied by a
      significant decrease of K+ concentration in cell water.

PMID- 16301817
TI  - Choline produces cytoprotective effects against ischemic myocardial injuries:
      evidence for the role of cardiac m3 subtype muscarinic acetylcholine receptors.
AB  - BACKGROUND/AIMS: Accumulating evidence indicates the presence of functional M3
      subtype of acetylcholine muscarinic receptors (M(3)-mAChR), in addition to the
      well-recognized M(2)-mAChR, in the heart of various species including man.
      However, the pathophysiological role of the cardiac M(3)-mAChR remain undefined.
      This study was designed to explore the possible role of M(3)-mAChR in
      cytoprotection of myocardial infarction and several related signaling pathways as
      potential mechanisms. METHODS: Studies were performed in a rat model of
      myocardial infarction and in isolated myocytes. RESULTS: We found that choline
      relieved myocardial injuries during ischemia or under oxidative stress, which was
      achieved by correcting hemodynamic impairment, diminishing ventricular
      arrhythmias and protecting cardiomyocytes from apoptotic death. The beneficial
      effects of choline were reversed by the M(3)-selective antagonists but not by the
      M(2)-selective antagonist. Choline/M(3)-mAChR activated several survival
      signaling molecules (antiapoptotic proteins Bcl-2 and ERKs), increased endogenous
      antioxidant reserve (SOD), and reduced apoptotic mediators (proapoptotic proteins
      Fas and p38 MAPK) and intracellular Ca2+ overload. CONCLUSION: Choline improves
      cardiac function and reduces ischemic myocardial injuries via stimulating the
      cardiac M(3)-mAChRs which in turn result in alterations of multiple signaling
      pathways leading to cytoprotection. The findings suggest M(3)-mAChR as a new
      target for drug development for improving cardiac function and preventing cardiac
      injuries during ischemia/reperfusion.

PMID- 16301818
TI  - Activation of beta3 adrenergic receptor decreases DNA synthesis in human skin
      fibroblasts via cyclic GMP/nitric oxide pathway.
AB  - BACKGROUND: Evidences have shown that beta1 and beta2 adrenoceptors co-exist in
      human fibroblasts, but it is not yet clear the functional expression of beta3
      adrenoceptor in these cells. The aim of this study was to investigate the
      expression and biological effect of beta3 adrenoceptor activation in human skin
      fibroblast and the different signaling pathways involved in its effect. METHODS:
      For this purpose in vitro cultures of human skin fibroblast were established from
      human foreskin and grown in Dulbecco's modified Eagle's medium. The effect of ZD
      7114 (beta3 agonist) on cell DNA synthesis, radioligand binding assay, cyclic GMP
      and cyclic AMP accumulation and nitric oxide synthase (NOS) activity were
      evaluated. RESULTS: 3H-CGP binding to human fibroblast membranes was a saturable
      process to a single class of binding site. The equilibrium parameters were: Kd
      20+/-3 pM and Bmax 222+/-19 fmol/mg protein. Ki values showed that these cells
      express a high number of beta(3)adrenoceptor subtypes. ZD 7114 stimulation of
      beta3 adrenoceptor exerts a concentration-dependent inhibition of DNA synthesis
      and cAMP accumulation with parallel increase in NOS activity that led to cGMP
      accumulation. All these effects were blocked by the beta3 adrenoceptor antagonist
      (SR 59230A). The effect of ZD 7114 on DNA synthesis significantly correlated with
      its action either on cAMP or NOS-cGMP signaling system. Inhibitors of NOS
      activity and NO-sensitive guanylate cyclase prevented the inhibitory effect of ZD
      7114 on DNA synthesis. In addition, the beta3 adrenoceptor-dependent increase in
      cGMP and activation of NOS were blocked by the inhibition of phospholipase C
      (PLC), calcium/calmodulin (CaM), endothelial NOS activity and cGMP accumulation.
      CONCLUSIONS: beta3 adrenoceptor activation exerts inhibitory effect on human
      fibroblast DNA synthesis as a result of the activation of NO-cGMP pathway and the
      inhibition of adenylate cyclase activity. The mechanism appears to occurs
      secondarily to stimulation of PLC and CaM. This in turn triggers cascade reaction
      leading to increase production of NO-cGMP with decrease in cAMP accumulation.

PMID- 16301819
TI  - Osmotic regulation of MG-132-induced MAP-kinase phosphatase MKP-1 expression in
      H4IIE rat hepatoma cells.
AB  - BACKGROUND/AIMS: Proteasome inhibitors such as MG-132 are considered as potential
      therapeutical tools in different clinical settings. The dual specificity MAP
      kinase phosphatase MKP-1 plays a role in balancing signals mediating cell death
      or survival. Here the effect of cell hydration on MG-132-induced MKP-1 expression
      was investigated in H4IIE rat hepatoma cells. RESULTS: Hyperosmolarity
      (405mosmol/l) increased MKP-1 expression by MG-132, which was accompanied by an
      induction of c-Fos, c-Jun, cJun Ser73 phosphorylation, and AP-1 DNA binding. MKP
      1 induction by MG-132 plus hyperosmolarity was sensitive to inhibition of
      p38(MAPK) and c-Jun-N-terminal kinases (JNKs) but not extracellular signal
      regulated kinases Erk-1/Erk-2, and was accompanied by a decline of MAP-kinase
      activities. Although hyperosmolarity increased overall protein ubiquitination in
      presence of MG-132, ubiquitination of MKP-1 was found under normo-, but not
      hyperosmotic conditions. Hyperosmolarity also enabled MG-132 to induce poly-ADP
      ribose polymerase (PARP) cleavage which was sensitive to inhibition of p38(MAPK)
      and JNKs but not Erk-1/Erk-2. PARP cleavage and caspase-3 activation in H4IIE
      cells treated with hyperosmolarity plus MG-132 was further increased by vanadate,
      consistent with a contribution of MKP-1 to counterbalance proapoptotic MAP-kinase
      signals. CONCLUSION: The findings suggest that among other factors cell hydration
      critically determines the cellular response to proteasome inhibitors.

PMID- 16301820
TI  - ERK-dependent signaling pathway and transcriptional factor Ets-1 regulate matrix
      metalloproteinase-9 production in transforming growth factor-beta1 stimulated
      glomerular podocytes.
AB  - The unregulated synthesis of glomerular basement membrane (GBM) components,
      extracelluar matrix (ECM) proteins, or the secretion of ECM-degradation enzymes,
      matrix metalloproteinases (MMPs), by podocytes under pathological conditions
      might be major factors in GBM damage. The present study examined the effects and
      the underlying molecular mechanism of transforming growth factor beta1 (TGFbeta1)
      on the production of gelatinase in cultured murine podocytes. Our results showed
      that TGFbeta1 is the most potent inducer of MMP-9 secretion in both a dose- and
      time-dependent manner, but has very little effect on MMP-2 secretion. TGFbeta1
      upregulated MMP-9 mRNA levels, but did not affect the expression of matrix
      mettaloproteinases TIMP-1 mRNA. TGFbeta1 induced activation of both Smad2 and
      extracellular signal-regulated kinases (ERK1/2). However, blockade of Smad2
      signaling pathway by Staurosporine did not affect the TGFbeta1-stimulated
      secretion of MMP-9, whereas inhibition of activation of ERK1/2 by PD98059
      abolished TGFbeta1-stimulated secretion of MMP-9 and expression of MMP-9 mRNA.
      Protein levels of the transcriptional factor Ets-1 increased and were sustained
      for 12 h by TGFbeta1-stimulation. Our data also showed that blockage of ERK1/2
      activation by PD98059 led to a reduction in the level of Ets-1 protein and to a
      consequent decrease in MMP-9 mRNA levels. These results demonstrate that TGFbeta1
      can induce the production of MMP-9 in podocytes through the ERK1/2 MAPK pathway,
      and suggested that an increase in MMP-9 enzymatic activities may be involved in
      the damage of the GBM in response to inflammatory factors, ultimately leading to
      glomerulosclerosis.

PMID- 16301822
TI  - Pregnancy effects on rat adipose tissue lipolytic capacity are dependent on
      anatomical location.
AB  - Pregnancy is characterized by changes in maternal adiposity. The aim of this
      study was to carry out a detailed analysis of the different steps of the
      adrenergic pathway, lipoprotein lipase (LPL) levels and adipocyte size, in order
      to evaluate the response of white adipose tissue (WAT) to the metabolic changes
      during pregnancy depending on the anatomical location. In general, the levels of
      the proteins of the lipolytic pathway decreased with pregnancy. In
      retroperitoneal WAT adenylate cyclase (AC) levels decreased from 100% in controls
      to 44% by day 13 and 11% by day 20. In mesenteric WAT the alpha (2A)/beta (3)
      adrenergic receptor balance seemed to be one of the main regulatory points of the
      lipolytic pathway and the reduction in the postreceptor element levels was
      clearly lower than for the other two depots (PKA levels reduced from 100% in
      controls to 72% by day 20, while in the other two depots it decreased to 30%, and
      AC and HSL levels did not show statistically significant changes in this depot).
      In contrast, the LPL-to-HSL ratio may be a major regulatory point in gonadal WAT.
      In summary, we describe regional differences in the regulation of WAT metabolism
      throughout pregnancy, which may be of great importance to determine the role of
      the different fat depots during late pregnancy. Thus, gonadal and mesenteric WAT
      changed to a lipolytic state to sustain the rapid foetal growth, although with
      differences between them in the main regulatory points, while retroperitoneal WAT
      could have a role later on, during lactation.

PMID- 16301821
TI  - Inhibition of insulin receptor gene expression and insulin signaling by fatty
      acid: interplay of PKC isoforms therein.
AB  - Fatty acids are known to play a key role in promoting the loss of insulin
      sensitivity causing insulin resistance and type 2 diabetes. However, underlying
      mechanism involved here is still unclear. Incubation of rat skeletal muscle cells
      with palmitate followed by I(125)- insulin binding to the plasma membrane
      receptor preparation demonstrated a two-fold decrease in receptor occupation. In
      searching the cause for this reduction, we found that palmitate inhibition of
      insulin receptor (IR) gene expression effecting reduced amount of IR protein in
      skeletal muscle cells. This was followed by the inhibition of insulin-stimulated
      IRbeta tyrosine phosphorylation that consequently resulted inhibition of insulin
      receptor substrate 1 (IRS 1) and IRS 1 associated phosphatidylinositol-3 kinase
      (PI3 Kinase), phosphoinositide dependent kinase-1 (PDK 1) phosphorylation. PDK 1
      dependent phosphorylation of PKCzeta and Akt/PKB were also inhibited by
      palmitate. Surprisingly, although PKCepsilon phosphorylation is PDK1 dependent,
      palmitate effected its constitutive phosphorylation independent of PDK1. Time
      kinetics study showed translocation of palmitate induced phosphorylated
      PKCepsilon from cell membrane to nuclear region and its possible association with
      the inhibition of IR gene transcription. Our study suggests one of the pathways
      through which fatty acid can induce insulin resistance in skeletal muscle cell.

PMID- 16301823
TI  - SGK1-mediated fibronectin formation in diabetic nephropathy.
AB  - The serum and glucocorticoid inducible kinase SGK1 has been shown to be up
      regulated in fibrosing tissue including diabetic nephropathy. The present study
      has been performed to determine the time course of SGK1 transcription in mouse
      kidneys following induction of diabetes by streptozotocin (STZ). Moreover, the
      study aimed to explore whether SGK1 may play an active role in the stimulation of
      matrix protein formation during hyperglycemia. The induction of diabetes in 8
      weeks old male C57Bl/6 mice was indeed followed by a significant (p< 0.001)
      increase of SGK1 transcript levels (up to 2.5-fold) and protein abundance (up to
      2.8-fold) both peaking 4 weeks after STZ treatment. The SGK1 transcript levels
      and protein abundance declined thereafter but remained significantly elevated up
      to 12 weeks (p<0.05). Exposure to high extracellular glucose concentration (25
      mM) significantly increased SGK1 transcript levels in human mesangial cells
      (HMCs). At low extracellular glucose concentration (5.5 mM), transfection with
      constitutively active (S422D)SGK1 and transdominant inhibitory (K127N)SGK1 did
      not significantly modify fibronectin formation by HMCs. Exposure to high
      extracellular glucose concentration stimulated fibronectin formation (by 2.2
      fold), an effect abrogated by transfection with inactive (K127N)SGK1 (1.2 fold)
      and markedly enhanced by transfection with (S422D)SGK1 (4.7 fold). In conclusion,
      hyperglycemia of diabetes mellitus leads to partially transient increase of SGK1
      transcription and translation. SGK1 overexpression alone has little effect on
      fibronectin formation but potentiates the effect of hyperglycemia. Thus, SGK1 is
      upregulated in diabetic nephropathy and actively participates in the stimulation
      of matrix protein deposition in this common deleterious complication of diabetic
      hyperglycemia.

PMID- 16301824
TI  - Identification and electrophysiological characteristics of isoforms of T-type
      calcium channel Ca(v)3.2 expressed in pregnant human uterus.
AB  - Electrophysiological characteristics were compared among four cloned human
      alpha1H isoforms transcripted by alternative splicings of exons 25B and 26
      [Delta25B/+26 (native form; alpha1H-a), Delta25B/Delta?6 (alpha1H-b),
      +25B/Delta26, and +25B/+26] in the intracellular loop between domains III and IV
      (III-IV linker) of a human T-type calcium channel (Ca(v)3.2). The native isoform
      Delta25B/+26 predominated in ovary and non-pregnant uterus, while isoform
      Delta25B/Delta26 (alpha1H-b) predominated in pregnant uterus and testis.
      Expressions of the newly identified +25B/Delta26 and +25B/+26 isoforms were
      greater in the uterus at gestation than in the non-pregnant uterus. When
      expressed in Xenopus laevis oocytes, all isoforms produced transient inward
      currents with low voltage-dependent activation and inactivation characterized in
      typical T-type Ca2+ currents. Each isoform possessing exon 25B (+25B/?Delta26 or
      +25B/+26) showed current activation and inactivation at a more negative membrane
      potential than the respective isoform (Delta25B/Delta26 or Delta25B/+26) lacking
      it. Moreover, the current activation and inactivation rates were faster for the
      two isoforms possessing exon 25B than for the respective isoforms lacking it. By
      itself, exon 26 seemed not to affect any electrophysiological characteristics.
      Increasing the net positive charge (relative to the native form), as occurred in
      isoforms Delta25B/Delta26, +25B/Delta26, and +25B/+26, caused recovery from short
      term inactivation to become faster. Our results show that molecular-structure
      variations within the III-IV linker influence the voltage-dependence and kinetics
      of both activation and inactivation. Although the role of T-type Ca2+ channels in
      uterine tissue remains unknown, changes in the uterine expression of these
      alpha1H isoforms may influence physiological functions during pregnancy.

PMID- 16301825
TI  - Regulation of KCNQ4 potassium channel prepulse dependence and current amplitude
      by SGK1 in Xenopus oocytes.
AB  - The KCNQ gene family comprises voltage-gated potassium channels expressed in
      epithelial tissues (KCNQ1, KCNQ5), inner ear structures (KCNQ1, KCNQ4) and the
      brain (KCNQ2-5). KCNQ4 is expressed in inner and outer hair cells of the inner
      ear where it determines electrical excitability. Accordingly, loss of function
      mutations of the KCNQ4 gene cause hearing loss. Several K+ channels including the
      closely related KCNQ1/KCNE1 channel are regulated by the serum- and
      glucocorticoid-inducible kinase (SGK) family. The present study utilized the
      Xenopus oocyte system to explore effects of SGK isoforms on KCNQ4 mediated K(+)
      currents: KCNQ4 channels activated in a voltage dependent manner with half
      maximal activation at -10 mV. The peak channel activity was significantly
      increased by prepulsing. Coexpression of wild type SGK1 but not coexpression of
      the inactive mutant (K127N)SGK1 significantly increased current amplitudes (by 67
      %) and significantly increased the resting potential of KCNQ4 expressing oocytes.
      Here we describe for the first time a prepulse dependence of KCNQ4 channels with
      increased currents after hyperpolarizing prepulses. Coexpression of SGK1
      significantly attenuated the effect of prepulsing on peak currents. Mutation of
      Ser to Asp or Ala in the putative phosphorylation consensus sequence in KCNQ4
      significantly decreased the sensitivity to SGK1-coexpression. In conclusion, SGK1
      regulates current amplitudes and kinetic properties of KCNQ4 channel activity, an
      effect sensitive to mutations in the SGK1 consensus sequence of the channel.

PMID- 16301826
TI  - Modulation of basal and peptide hormone-stimulated Na transport by membrane
      cholesterol content in the A6 epithelial cell line.
AB  - These studies examined the effect of altering plasma membrane cholesterol on
      basal Na+ flux as well as on the natriferic responses to the peptide hormones,
      insulin and anti-diuretic hormone (ADH) in the A6 model renal cell line. Membrane
      cholesterol concentrations were depleted or enriched using methyl-beta
      cyclodextrin (MbetaCD) or a MbetaCD/cholesterol inclusion complex respectively.
      Effects of changes in the apical and basolateral plasma membranes were examined
      independently. Apical membrane cholesterol removal or supplementation had no
      effect on the basal Na+ transport rate. Short-term apical membrane cholesterol
      supplementation also had no effect on insulin-stimulated Na+ transport or on the
      initial phase of the ADH response. Interestingly, the additional apical membrane
      cholesterol had an inhibitory effect on the ADH response after 30 minutes. Apical
      membrane cholesterol depletion partially inhibited the responses to both insulin
      and ADH. Conversely, supplementation of basolateral cholesterol caused a
      significant increase in basal Na+ flux. Removal of cholesterol from the
      basolateral plasma membrane caused a decrease in basal Na+ flux with a time
      course analogous to channel turnover and completely inhibited peptide hormone
      responses. None of the changes in membrane cholesterol content decreased
      transcellular resistance. These results indicate an important role for membrane
      cholesterol content in the regulation of ENaC-mediated Na+ uptake.

PMID- 16301827
TI  - Functional and molecular adaptation of Cl/HCO3- exchanger to chronic alkaline
      media in renal cells.
AB  - The Cl(-)/HCO3- exchanger (AE) is one of the mechanisms that cells have developed
      to adjust pH Despite its importance, the role of AE isoforms in controlling
      steady-state pH during alkalosis has not been widely investigated. In the present
      study, we have evaluated whether conditions simulating acute and chronic
      metabolic alkalosis affected the transport activity and protein levels of Cl
      /HCO3- exchangers in a rat cortical collecting duct cell line (RCCD1). pH(i) was
      monitored using the fluorescent dye BCECF in monolayers grown on permeable
      supports. Anion exchanger function was assessed by the response of pH(i) to acute
      chloride removal. RT-PCR and immunoblot assays were also performed. Our results
      showed that RCCD1 cells express two members of the anion exchanger gene family:
      AE2 and AE4. Functional studies demonstrated that while in acute alkalosis pH(i)
      became alkaline and was not regulated, after 48 h adaptation; steady-state pH(i)
      reached a value similar to the physiological one. Chronic treated cells also
      resulted in a 3-fold rise in Cl(-)/HCO3- exchange activity together with a 2.2
      fold increase in AE2, but not AE4, protein abundance. We conclude that RCCD1
      cells can adapt to chronic extracellular alkalosis reestablishing its steady
      state pH(i) and that AE2 would play a key role in cell homeostasis.

PMID- 16301828
TI  - Establishment and characterization of a novel polarized MDCK epithelial cellular
      model for CFTR studies.
AB  - F508del is the most common mutation in the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene that is responsible for the genetic disease
      Cystic Fibrosis (CF). It results in a major failure of CFTR to traffic to the
      apical membrane of epithelial cells, where it should function as a chloride (Cl-)
      channel. Most studies on localization, processing and cellular trafficking of
      wild-type (wt) and F508del-CFTR have been performed in non-epithelial cells.
      Notwithstanding, polarized epithelial cells possess distinctly organized and
      regulated membrane trafficking pathways. We have used Madin-Darby canine kidney
      (MDCK) type II cells (proximal tubular cells which do not express endogenous
      CFTR) to generate novel epithelial, polarized cellular models stably expressing
      wt- or F508del-CFTR through transduction with recombinant lentiviral vectors.
      Characterization of these cell lines shows that wt-CFTR is correctly processed
      and apically localized, producing a cAMP-activated Cl- conductance. In contrast,
      F508del-CFTR is mostly detected in itsimmature form, localized intracellularly
      and producing only residual Cl- conductance. These novel cell lines constitute
      bona fide models and significantly improved resources to investigate the
      molecular mechanisms of polarized membrane traffic of wt- and F508del-CFTR in the
      same cellular background. They are also useful to identify/validate novel
      therapeutic compounds for CF.

PMID- 16301829
TI  - Introduction. Critical role of anti-angiogenesis and VEGF inhibition in
      colorectal cancer.

PMID- 16301830
TI  - VEGF as a key mediator of angiogenesis in cancer.
AB  - Vascular endothelial growth factor (VEGF) is a homodimeric glycoprotein with a
      molecular weight of approximately 45 kDa. It is the key mediator of angiogenesis
      (the formation of new blood vessels), and binds two VEGF receptors (VEGF receptor
      1 and VEGF receptor-2), which are expressed on vascular endothelial cells. In
      healthy humans, VEGF promotes angiogenesis in embryonic development and is
      important in wound healing in adults. VEGF is the key mediator of angiogenesis in
      cancer, in which it is up-regulated by oncogene expression, a variety of growth
      factors and also hypoxia. Angiogenesis is essential for cancer development and
      growth: before a tumor can grow beyond 1-2 mm, it requires blood vessels for
      nutrients and oxygen. The production of VEGF and other growth factors by the
      tumor results in the 'angiogenic switch', where new vasculature is formed in and
      around the tumor, allowing it to grow exponentially. Tumor vasculature formed
      under the influence of VEGF is structurally and functionally abnormal. Blood
      vessels are irregularly shaped, tortuous, have dead ends and are not organized
      into venules, arterioles and capillaries. They are also leaky and hemorrhagic,
      which leads to high interstitial pressure. These characteristics mean that tumor
      blood flow is suboptimal, resulting in hypoxia and further VEGF production. This
      central role of VEGF in the production of tumor vasculature makes it a rational
      target for anticancer therapy.

PMID- 16301831
TI  - VEGF as a therapeutic target in cancer.
AB  - Tumors require nutrients and oxygen in order to grow, and new blood vessels,
      formed by the process of angiogenesis, provide these substrates. The key mediator
      of angiogenesis is vascular endothelial growth factor (VEGF), which is induced by
      many characteristics of tumors, most importantly hypoxia. Therefore, VEGF is an
      appealing target for anticancer therapeutics. In addition, VEGF is easy to access
      as it circulates in the blood and acts directly on endothelial cells. VEGF
      mediated angiogenesis is rare in adult humans (except wound healing and female
      reproductive cycling), and so targeting the molecule should not affect other
      physiological processes. Tumor blood vessels, formed under the influence of VEGF,
      are disorganized, tortuous and leaky with high interstitial pressure, reducing
      access for chemotherapies. Inhibiting VEGF would reduce the vessel abnormality
      and increase the permeability of the tumor to chemotherapies. Several approaches
      to targeting VEGF have been investigated. The most common strategies have been
      receptor-targeted molecules and VEGF-targeting molecules. The disadvantage of
      receptor-targeted approaches is that the VEGF receptors also bind different
      members of the VEGF super-family and affect systems other than angiogenesis. The
      best-studied and most advanced approach to VEGF inhibition is the humanized
      monoclonal antibody bevacizumab (Avastin), which is the only anti-angiogenic
      agent approved for treatment of cancer.

PMID- 16301832
TI  - Bevacizumab combined with standard fluoropyrimidine-based chemotherapy regimens
      to treat colorectal cancer.
AB  - For several decades, 5-fluorouracil (5-FU) with or without leucovorin defined the
      standard of care for the treatment of metastatic colorectal cancer (CRC). The
      addition of other chemotherapy regimens to 5-FU has improved survival, but often
      at the expense of increased toxicity. Recent advances in our understanding of the
      molecular basis of CRC have led to the production of novel targeted agents, such
      as bevacizumab (Avastin). Bevacizumab is currently approved for the first-line
      treatment of metastatic CRC and is currently being tested in combination with
      standard therapies for a range of indications. Phase II/III trials have
      demonstrated that the addition of bevacizumab to 5-FU-based first-line
      chemotherapy improves survival, progression-free survival and response rate
      compared with chemotherapy alone. Combination therapy does not appear to
      exacerbate side effects known to be associated with the chemotherapy regimen. The
      most common side effects attributable to bevacizumab therapy include
      hypertension, proteinuria and bleeding. Although uncommon, gastrointestinal
      perforation and arterial thromobembolic events are the most serious side effects
      reported to date. Bevacizumab is currently being evaluated in combination with
      oxaliplatin (Eloxatin)-based therapies and preliminary data are encouraging.
      Ongoing trials of bevacizumab in combination with standard first-line
      chemotherapy regimens will evaluate bevacizumab's potential in a range of cancer
      types. .

PMID- 16301834
TI  - The future development of bevacizumab in colorectal cancer.
AB  - Bevacizumab (Avastin), the first approved therapy designed to inhibit tumor
      angiogenesis, has significant clinical benefits in the management of colorectal
      cancer (CRC). When bevacizumab is added to IFL (5-fluorouracil [5-FU]/leucovorin
      [LV]/irinotecan [Camptosar)]) as first-line therapy for metastatic CRC,
      significant overall and progression-free survival benefits are obtained. Similar
      survival benefits may be achieved when bevacizumab is added to 5-FU/LV alone. In
      addition, additive and synergistic effects with a range of chemotherapeutic
      agents illustrate that bevacizumab has considerable potential in combination with
      existing therapeutic options. Clinical data indicate that bevacizumab is the only
      agent in addition to chemotherapy that has demonstrated survival benefit in the
      first- and second-line settings. In addition, bevacizumab is expected to produce
      clinical benefit in the adjuvant setting: inhibition of vascular endothelial
      growth factor should prevent the angiogenic switch in micrometastases, which is a
      key factor in malignancy. The clinical program is examining the activity of
      bevacizumab in combination with the likely future standard of care in both the
      metastatic and adjuvant treatment settings. Phase III trials (NO16966C, CONcePT
      and TREE-2) are studying the benefit of combining bevacizumab with oxaliplatin
      (Eloxatin)-based regimens. Similarly, in the adjuvant setting, phase III trials
      are assessing the efficacy and tolerability of bevacizumab in combination with
      oxaliplatin-based chemotherapy (AVANT, NSABP C-08).

PMID- 16301833
TI  - Managing patients treated with bevacizumab combination therapy.
AB  - The anti-angiogenic agent bevacizumab (Avastin) has been rationally designed to
      target vascular endothelial growth factor (VEGF), a key mediator of tumor
      angiogenesis. Based on its limited roles in adults, VEGF inhibition using
      bevacizumab would be expected to have limited side effects. Furthermore, because
      its mechanism of action is different to that of standard chemotherapeutic agents,
      bevacizumab would not be expected to cause typical cytotoxic agent-related
      toxicity or to exacerbate the toxicity of concomitant chemotherapy. We have
      reviewed clinical trials published to date, primarily in metastatic colorectal
      cancer, and describe the safety profile of bevacizumab. The review focuses on
      hypertension, proteinuria, arterial thrombosis, effects on wound healing,
      bleeding and gastrointestinal (GI) perforation, which are the principal
      bevacizumab-related events seen in clinical trials. These events are for the most
      part mild to moderate in severity and clinically manageable (hypertension,
      proteinuria, minor bleeding) or occur uncommonly (wound healing complications, GI
      perforations and arterial thrombosis). The side-effect profile of bevacizumab
      makes it a suitable adjunct to standard chemotherapy in settings where efficacy
      has been demonstrated, and it is now approved for use in the USA, the European
      Union and other markets worldwide.

PMID- 16301835
TI  - Investigating the potential of bevacizumab in other indications: metastatic renal
      cell, non-small cell lung, pancreatic and breast cancer.
AB  - Bevacizumab (Avastin) has unprecedented survival benefit in patients with
      metastatic colorectal cancer. Trials are already in progress to investigate the
      potential of bevacizumab in indications including metastatic renal cell cancer
      (RCC), non-small cell lung cancer (NSCLC), pancreatic cancer, breast and ovarian
      cancer. Bevacizumab offers the potential to increase survival without
      substantially altering the toxicity profile in these tumor types. Bevacizumab has
      shown activity in patients with refractory metastatic RCC, where progression-free
      survival (PFS) was significantly longer in patients treated with bevacizumab (10
      mg/kg every 2 weeks) than those treated with placebo (hazard ratio=2.55,
      p<0.001). In addition, combining bevacizumab with erlotinib (Tarceva) has shown a
      median time to progression of more than 11 months. In NSCLC, a phase II trial
      revealed that adding bevacizumab to chemotherapy increased therapeutic benefit
      compared with chemotherapy alone. Adverse events were mild and easily managed,
      but six patients receiving bevacizumab developed severe hemoptysis. Entry
      criteria for NSCLC trials have been adjusted to exclude patients with squamous
      cell histology to try to avoid this issue. Adding bevacizumab (10 mg/kg) to the
      current standard of care, gemcitabine, in stage IV pancreatic cancer has also
      shown promising efficacy. Partial responses were seen in 19% of patients, with a
      further 48% having stable disease. Several ongoing clinical trials are also
      studying bevacizumab with various chemotherapy and radiotherapy regimens.
      Bevacizumab combined with carboplatin (Paraplatin)/paclitaxel (Taxol) was further
      examined in a phase III randomized trial that accrued 878 patients with advanced
      non-squamous cell NSCLC. Patients given chemotherapy (paclitaxel and carboplatin)
      plus bevacizumab had a higher response rate, longer PFS and an increase in
      survival compared with patients on chemotherapy alone. Both regimens were
      generally well tolerated. Bevacizumab has also shown activity in patients with
      metastatic breast cancer. In 715 patients, a significant, 2-fold increase in
      response rate was observed in patients receiving bevacizumab plus paclitaxel
      compared with paclitaxel alone. Median PFS was also significantly increased
      (p<0.001). Bevacizumab has the potential to provide significant efficacy benefits
      for patients with metastatic RCC, NSCLC, pancreatic cancer, and other tumor types
      when used first line in combination with standard therapy.

PMID- 16301836
TI  - Neuroprotective role of vascular endothelial growth factor: signalling
      mechanisms, biological function, and therapeutic potential.
AB  - Vascular endothelial growth factor (VEGF or VEGF-A) and its receptors play
      essential roles in the formation of blood vessels during embryogenesis and in
      disease. Most biological effects of VEGF are mediated via two receptor tyrosine
      kinases, VEGFR1 and VEGFR2, but specific VEGF isoforms also bind neuropilins (NP)
      1 and 2, non-tyrosine kinase receptors originally identified as receptors for
      semaphorins, polypeptides with essential roles in neuronal patterning. There is
      abundant evidence that VEGF-A has neurotrophic and neuroprotective effects on
      neuronal and glial cells in culture and in vivo, and can stimulate the
      proliferation and survival of neural stem cells. VEGFR2 and NP1 are the major
      VEGF receptors expressed on neuronal cells and, while the mechanisms mediating
      neuroprotective effects of VEGF are not fully understood, VEGF stimulates several
      signalling events in neuronal cell types, including activation of phospholipase C
      gamma, Akt and ERK. Findings in diverse models of nerve damage and disease
      suggest that VEGF has therapeutic potential as a neuroprotective factor. VEGF is
      a key mediator of the angiogenic response to cerebral and peripheral ischaemia,
      and promotes nerve repair following traumatic spinal injury. Recent work has
      revealed a role for reduced VEGF expression in the pathogenesis of amyotrophic
      lateral sclerosis, a rare neurodegenerative disease caused by selective loss of
      motor neurons. In many instances, the neuroprotective effects of VEGF appear to
      result from a combination of the indirect consequences of increased angiogenesis,
      and the direct stimulation of neuronal function. However, more work is required
      to determine the specific functional role of direct neuronal effects of VEGF.

PMID- 16301837
TI  - Postnatal changes in functional activities of the pig's brain: a combined
      functional magnetic resonance imaging and immunohistochemical study.
AB  - Developmental changes in brain activation after pain stimulation and after
      passive movement of the hind paw were assessed by functional magnetic resonance
      imaging (fMRI) in pigs of postnatal ages 2, 4 and 6 months. Response patterns
      were correlated with histological maturation parameters. At 2 months, fMRI failed
      to detect brain activation after pain stimulation and revealed weak, but
      widespread activation after passive movement. At 4 months, strong reaction of
      numerous cortical areas on the contralateral side was seen after pain
      stimulation. Following passive movement, activation was weaker but more
      widespread, and the brainstem was also involved. By 6 months, cortical activation
      became more restricted to the contralateral sensory cortex and brainstem after
      pain stimulation and to the contralateral sensory and ipsilateral premotor and
      motor cortices after passive movement. Neocortical synaptophysin immunoreaction
      increased significantly between 2 and 4 months and slightly decreased by 6
      months. The density of GABA-immunoreactive neurons and fibers significantly
      increased, reaching a maximum at 6 months. Our studies indicate that remodeling
      of synapses and development of inhibitory GABA neurons last until 6 months
      postnatally, when the fMRI response of the pig's brain also attains its mature
      adult pattern.

PMID- 16301838
TI  - Neurons in the rat lateral hypothalamic area integrate information from the
      gastric vagal nerves and the cerebellar interpositus nucleus.
AB  - Previous investigations have demonstrated that the neuronal activity in the
      lateral hypothalamic area (LHA) is respectively modulated by afferent inputs from
      the gastric vagal nerves innervating the upper gastrointestinal tract, as well as
      the cerebellar interpositus nucleus (IN). The aim of this study was to examine
      whether the gastric vagal and cerebellar IN inputs converge onto single LHA
      neurons in rats, especially those sensitive to glycemia. Of the 114 LHA neurons
      recorded, 60 (52.6%) and 51 (44.7%) responded to gastric vagal and cerebellar IN
      stimulation, respectively. Of the 60 LHA neurons responsive to gastric vagal
      stimulation, 30 also responded to the cerebellar IN stimulus, indicating a
      convergence of gastric vagal and cerebellar inputs onto single hypothalamic
      cells. When the gastric vagal nerves and cerebellar IN were stimulated
      simultaneously, a summation of the responses was observed in all 6 neurons
      tested. Moreover, of 24 neurons that responded to both the gastric vagal and
      cerebellar IN stimuli, 15 (62.5%) were identified as glycemia-sensitive. These
      results demonstrate that the visceral information transmitted by the gastric
      vagal nerves and the somatic information forwarded by the cerebellar IN converge
      onto single LHA neurons, especially those sensitive to glycemia. The findings
      also suggest that integration of somatic-visceral responses related to short-term
      feeding regulation may take place in the LHA.

PMID- 16301839
TI  - Calcium signals activated by arachidonic acid in embryonic chick ciliary ganglion
      neurons.
AB  - Arachidonic acid (AA, 20:4) has been reported to modulate a variety of calcium
      permeable ionic channels, both in the plasma membrane and in the endoplasmic
      reticulum. We have studied the effects of AA on calcium signaling in a well
      characterized model of developing peripheral neurons, embryonic chick ciliary
      ganglion neurons in culture. When given at low non-micellar concentrations (5
      microM), in the majority of cells AA directly activated a delayed and long
      lasting increase in [Ca2+]i, involving both the cytoplasm and the nucleoplasm,
      that was completely reversed by abolition of extracellular calcium. Other fatty
      acids (FAs), either saturated like arachidic acid (20:0), or unsaturated like
      linoleic (18:2) and docosahexaenoic acid (22:6), shared its ability to activate
      calcium influx. This entry was not suppressed by voltage-dependent calcium
      channel inhibitors omega-conotoxin and nifedipine, by the voltage-independent
      calcium channel antagonist LOE-908, by pre-treatment with blockers of AA
      metabolic pathways or with pertussis toxin. The arachidonate-activated calcium
      pathway was permeable to Mn2+ and blocked by La3+, Gd3+ and Ni2+. In a neuronal
      subpopulation, AA at the same concentration was also able to elicit calcium
      release from thapsigargin-sensitive intracellular stores; we provide evidence
      that cytochrome P450 epoxygenase is involved in this process.

PMID- 16301840
TI  - Alterations of hypoxia-inducible factor-1 alpha in the hippocampus of mice
      acutely and repeatedly exposed to hypoxia.
AB  - This work aims at investigating the effects of hypoxic preconditioning on hypoxia
      inducible factor-1 alpha (HIF-1alpha) expression in the hippocampus of mice
      during acute and repeated hypoxic exposures. The mice were randomly divided into
      three groups and exposed, respectively, to hypoxia for 4 runs (group H4), 1 run
      (group H1), and 0 run (group H0). Reverse transcription-polymerase chain reaction
      (RT-PCR), Western blot, electrophoretic mobility shift assay (EMSA), and
      chromatin immunoprecipitation were used to examine the HIF-1alpha responses in
      the mouse hippocampus following exposure to hypoxia. The tolerance of mice to
      hypoxia increased significantly following acute and repetitive exposure to
      autoprogressive hypoxia. Total mRNA, total protein, and nuclear protein were
      extracted from the hippocampus for RT-PCR, Western blot, and EMSA, respectively.
      The HIF-1alpha mRNA levels were found to be increased in group H1 and decreased
      in group H4. The HIF-1alpha protein levels and HIF-1 DNA-binding activities were
      increased in group H1 and markedly increased in group H4. One of the HIF-1 target
      genes, vascular endothelial growth factor, increased in group H4. HIF-1
      activation is thought to be involved in the protection of the brain of hypoxic
      preconditioned mice.

PMID- 16301841
TI  - Protein kinase A and Ca(v)1 (L-Type) channels are common targets to facilitatory
      adenosine A2A and muscarinic M1 receptors on rat motoneurons.
AB  - At the rat motor endplate, pre-synaptic facilitatory adenosine A2A and muscarinic
      M1 receptors are mutually exclusive. We investigated whether these receptors
      share a common intracellular signalling pathway. Suppression of McN-A-343-induced
      M1 facilitation of [3H]ACh release was partially recovered when CGS21680C (an A2A
      agonist) was combined with the cyclic AMP antagonist Rp-cAMPS. Forskolin,
      rolipram and 8-bromo-cyclic AMP mimicked CGS21680C blockade of M1 facilitation.
      Both Rp-cAMPs and nifedipine reduced augmentation of [3H]ACh release by McN-A-343
      and CGS21680C. Activation of M1 and A2A receptors enhanced Ca2+ recruitment
      through nifedipine-sensitive channels. Nifedipine inhibition revealed by McN-A
      343 was prevented by chelerythrine (a PKC inhibitor) and Rp-cAMPS, suggesting
      that Ca(v)1 (L-type) channels phosphorylation by PKA and PKC is required. Rp
      cAMPS inhibited [3H]ACh release in the presence of phorbol 12-myristate 13
      acetate, but PKC inhibition by chelerythrine had no effect on release in the
      presence of 8-bromo-cyclic AMP. This suggests that the involvement of PKA may be
      secondary to M1-induced PKC activation. In conclusion, competition of M1 and A2A
      receptors to facilitate ACh release from motoneurons may occur by signal
      convergence to a common pathway involving PKA activation and Ca2+ influx through
      Ca(v)1 (L-type) channels.

PMID- 16301842
TI  - Umbilical cord levels of interleukin-1 receptor antagonist and neonatal outcome.
AB  - BACKGROUND: Previous studies indicate that there may be infant gender differences
      in cytokine expression associated with differences in neonatal morbidity.
      OBJECTIVE: We tested the hypothesis that umbilical cord interleukin-1 receptor
      antagonist (IL-1ra) correlates with infant gender and neonatal outcome in preterm
      infants. STUDY DESIGN: IL-1ra was measured in cord blood taken from 58 preterm
      infants (33 males, 25 females) with gestational age less than 32 weeks. Receiver
      operating characteristics (ROC) curve were used for identifying IL-1ra values
      with high sensitivity and specificity for neonatal morbidity and adverse outcome,
      i.e., death or survival with severe intraventricular hemorrhage or
      periventricular leukomalacia. RESULTS: In the female infants, but not the male
      infants, cord IL-1ra values correlated with postnatal depression, expressed as
      Apgar scores at 1 min (correlation coefficient, r(s); p value: -0.542; 0.005), 5
      min (-0.571; 0.018), and 10 min (-0.442; 0.035); and postnatal age at intubation
      (-0.799; 0.001). The ROC area under the curve (AUC) was 0.735 for adverse outcome
      (p=0.013), and 0.683 for bronchopulmonary dysplasia (p=0.021) when all infants
      were included. However, there was a significant gender difference in the ROC
      curve for adverse outcome (p=0.026), with AUC 0.640 (p=0.240) in males and AUC
      0.929 (p=0.008) in females. Above a chosen cutoff at 13,500 ng/l for IL-1ra cord
      the sensitivity and specificity for predicting adverse outcome was 100 and 81%,
      respectively in females versus 50 and 84% in males. CONCLUSION: Increased levels
      of cord IL-1ra levels are associated with neonatal morbidity and adverse outcome
      in preterm infants. Comparable levels of IL-1ra have different predictive value
      depending on infant gender.

PMID- 16301843
TI  - [Pseudomembranous colitis after 5-fluorouracil chemotherapy in rectal cancer
      patient].

PMID- 16301844
TI  - [Pancreatitis--etiology and pathogenesis].
AB  - Pancreatic inflammatory disease can be classified as acute pancreatitis (AP) and
      chronic pancreatitis (CP) primarily by clinical criteria, with an obvious
      difference by restoration of normal function in the former or by permanent
      residual damage in the latter. Gallstones and alcohol are the most common causes
      of AP. Recent investigations have established that AP from all cause may disrupt
      normal stimulus-secretion coupling function within the acinar cell. This
      disruption within the acinar cell leads to an event termed 'co-localization' in
      which the digestive and lysosomal enzymes merge resulting in a premature
      activation of proteases. The mechanisms of inflammatory cells which adhere to
      endothelial cell are determined by a variety of mediators of cytokines released
      at the site of tissue damage. Cytokines hold the key for both local and systemic
      inflammatory response in AP. Besides, CP is a debilitating disease characterized
      by progressive and irreversible destruction of pancreatic tissue leading to
      exocrine and endocrine insufficiencies. Alcohol intake is the most common cause
      of CP. Mutations in the cationic trypsinogen gene were identified as causative
      gene for hereditary pancreatitis. The recognition of frequent cystic fibrosis
      transmembrane conductance regulator (CFTR) mutations and serine protease
      inhibitor, Kazal type 1 (SPINK1) mutations in idiopathic CP has hightened the
      awareness of importance of genetic mutations in CP. Pancreatic stellate cells
      represent the main cellular source of extracellular matrix in CP and play a key
      role in pancreatic fibrosis.

PMID- 16301845
TI  - [Diagnosis and predicting severity in acute pancreatitis].
AB  - Acute pancreatitis is an inflammatory disease of pancreas which come from various
      etiologies. The pathologic spectrum of acute pancreatitis varies from mild
      edematous pancreatitis to severe necrotizing pancreatitis. To diagnose and to
      predict severity in acute pancreatitis, various biochemical marker, imaging
      modalities and clinical scoring system are needed. Ideal parameters should be
      accurate, be performed easily and enable earlier assess. Unfortunately, no ideal
      parameter is available up to date. Serum amylase and lipase are still useful for
      the diagnosis but meaningless in predicting severity. C-reactive protein and
      inflammatory cytokines are promising single parameters to predict the severity.
      CT finding is also an useful determinant of severity, but is expensive and is
      delayed in assessment.

PMID- 16301846
TI  - [Medical management of acute pancreatitis and complications].
AB  - Medical management of acute pancreatitis relies on supportive care such as fluid
      resuscitation and pain control. Prophylactic antibiotics can reduce the
      opportunity of infection in severe pancreatitis. The effect of somatostatin or
      protease inhibitors still needs to be evaluated through further study. Early
      endoscopic retrograde cholangiopancreatography (ERCP) can ameliorate the course
      of severe biliary pancreatitis. Although sterile pancreatic necrosis, acute fluid
      collection, and pseudocyst usually resolve spontaneously, endoscopic or
      percutaneous drainages are needed when these complications are infected.

PMID- 16301847
TI  - [Natural course and medical treatment of chronic pancreatitis].
AB  - Chronic pancreatitis is a progressive disease without curative treatment.
      Abdominal pain is the most predominant symptom of chronic pancreatitis that
      initially brings most of the patients to the physician's attention. Some studies
      have correlated the course of pain in chronic pancreatitis in comparison with the
      duration of the disease, progressing exocrine and endocrine pancreatic
      insufficiency, and morphological changes such as pancreatic calcification and
      duct abnormalities. Furthermore, the course of pain has been studied after
      alcohol abstinence or surgery in some groups. However, there are only few well
      performed and valid studies, and some of them even have produced diversing
      results, in part. Further controlled studies harboring a large number of patients
      in a multicenter setting should be considered. Therapeutic efforts on chronic
      pancreatitis have focused on palliative treatment of pain which is present in
      about 80% of cases. Endoscopic treatment of pain in chronic pancreatitis is
      useful and feasible in many patients. Selecting candidate for endotherapy is
      mandatory. Main indication of pancreatic stent insertion in chronic pancreatitis
      is the presence of an obvious ductal stricture. Complications of chronic
      pancreatitis are also indications of endoscopic intervention. Exocrine and
      endocrine insufficiencies should be meticulously managed to prevent complications
      and to maintain good quality of life.

PMID- 16301848
TI  - [Surgical treatment of pancreatitis].
AB  - The management of pancreatitis remained controversial over the past decades,
      varying from conservative medical treatment to surgical treatment. However, in
      recent years, treatment of severe acute pancreatitis is shifting from an early
      surgical debridement and necrosectomy to an aggressive intensive medical care.
      While the treatment is conservative in the earlier phase of the disease, surgery
      might be considered in the later phase. In chronic pancreatitis and in pancreatic
      pseudocyst, various surgical approaches are available these days. Apart from the
      conventional open surgery, laparoscopic procedure became popular since it is
      minimally invasive and effective. In addition, with the great improvements in
      interventional radiology and endoscopic techniques, multidisciplinary approaches
      including medical, interventional, and surgical management become much more
      important in the proper treatment of pancreatitis. In this review, pancreatitis
      is classified into three categories (acute pancreatitis, chronic pancreatitis,
      and pancreatic pseudocyst) for convenience, and the surgical treatment is
      described in each category.

PMID- 16301849
TI  - [Hereditary pancreatitis].
AB  - The first family of hereditary pancreatitis was described in 1952. The mode of
      inheritance is autosomal dominant trait with an 80% of penetrance rate. Although
      hereditary pancreatitis is rare, this disorder has provided valuable insights in
      understanding the pathophysiology of pancreatitis and pancreatic cancer. The
      causative gene of hereditary pancreatitis was identified in 1996 through
      mutational analysis of genes within chromosome 7q35. Most forms of hereditary
      pancreatitis are caused by one of two common mutations, R122H in the third exon
      or N29I in the second exon of the cationic trypsinogen gene (protease serine 1,
      PRSS1). R122H mutation is the most common PRSS1 mutation. Additional mutations of
      the cationic trypsinogen gene have been described. In Korea, first family of
      hereditary pancreatitis with cationic trypsinogen gene mutation revealed an
      arginine to histidine amino acid substitution at the residue 122. Patients with
      hereditary pancreatitis present with symptoms at an early age and have
      significant risk for the development of chronic pancreatitis and pancreatic
      cancer. The risk of pancreatic cancer is estimated to be 53-fold higher after the
      age of 50 years than the general population. The risk of pancreatic cancer is not
      related to the type of mutation. Since hereditary pancreatitis is a strong risk
      factor for pancreatic cancer, it is important to establish a diagnostic criteria
      for diagnosis and surveillance. However, there are potential benefits, risks and
      limitations in genetic testing for hereditary pancreatitis. It is difficult to
      provide the proper treatment, but recent developments in therapeutic approaches
      may be helpful in caring hereditary pancreatitis. This article includes the
      current status, pathogenesis, clinical features, and management of hereditary
      pancreatitis including the aspects of pancreatic cancer.

PMID- 16301850
TI  - [Effectiveness of triple therapy and quadruple therapy for Helicobacter pylori
      eradication].
AB  - BACKGROUND/AIMS: Quadruple therapy can be considered as a first-line therapy in
      areas where the resistance rate to clarithromycin is high. Comparison study of
      triple therapy and quadruple therapy for Helicobacter pylori (H. pylori)
      eradication is still lacking in Korea despite the increasing prevalence of
      antibiotic resistance. This study was conducted to compare the efficacy of triple
      and quadruple therapy as a first-line treatment in H. pylori infected patients
      with peptic ulcer. METHODS: Consecutive 149 cases of peptic ulcer disease
      associated with H. pylori infection were randomized either to proton pump
      inhibitor (PPI, bid), amoxicillin (1,000 mg, bid), and clarithromycin (500 mg,
      bid) (PAC group) or to PPI (bid), bismuth subcitrate (300 mg, qid), metronidazole
      (500 mg, tid), and tetracycline (500 mg, qid) (PBMT group) eradication treatments
      for 7 days. Outcome of eradication therapy was assessed by 13C-urea breath test
      performed 4-6 weeks after eradication. RESULTS: Eradication rates in PAC and PBMT
      group were 78.7% (59/75) and 71.6% (53/74) by intention to treat analysis,
      respectively (p=0.424). By per protocol analysis, eradication rates of PAC and
      PBMT group were 85.5% (59/69) and 85.5% (53/62), respectively (p=1.012). Adverse
      reactions occurred in 5 (6.6%) and 7 (9.5%) patients in PAC and PBMT group,
      respectively (p=0.346). CONCLUSIONS: One week-quadruple therapy as a first-line
      treatment for H. pylori infection does not offer any advantage over PPI-based
      triple therapy in Korean patients.

PMID- 16301851
TI  - [The influence of non-steroidal anti-inflammatory drugs on clinical outcome in
      patients with bleeding peptic ulcers].
AB  - BACKGROUND/AIMS: We conducted this study to find the clinical characteristics of
      ulcer bleeding that occurred in patients who had been taking non-steroidal anti
      inflammatory drugs (NSAIDs) and to evaluate the influences of NSAIDs on clinical
      outcomes. METHODS: Between January 2000 and December 2002, a total of 310
      patients with ulcer bleeding were analyzed. Study group composed of 49 patients
      who had taken NSAIDs regularly for at least 4 weeks before the admission. Other
      261 patients who had not taken NSAIDs were classified as control group. Relevant
      informations were obtained from the medical records. RESULTS: Of the NSAIDs
      group, aspirin was the most common medication. The mean age and the proportion of
      females in the NSAIDs group were significantly higher than those of the control
      group. Prevalence of co-morbid illness was significantly higher in the NSAIDs
      group than in the control group (85.7% vs 30.7%, p<.001). The severity of
      bleeding which was assessed by hemoglobin level at presentation, amount of
      transfusion, and duration of admission, was not different between two groups.
      There were no significant differences in frequency of re-bleeding, urgent
      surgery, and mortality. CONCLUSIONS: Ulcer bleeding among patients taking NSAIDs
      occurred more frequently in older females with co- morbid illness. However,
      NSAIDs is not associated with higher morbidity and mortality.

PMID- 16301852
TI  - [Colonoscopic surveillance after curative resection for colorectal cancer with
      synchronous adenoma].
AB  - BACKGROUND/AIMS: Guidelines for current postoperative colonoscopic surveillance
      are not specified in colorectal cancer (CRC) patients with synchronous adenoma
      (SA). We performed this retrospective study to determine the postoperative
      colonoscopic surveillance interval for the CRC patients with SA. METHODS: One
      hundred and twenty-four CRC patients with SA (SA-group) and the same number of
      patients without SA (NSA-group) were selected from our database. Two groups were
      matched by the stage of CRC. Median colonoscopic surveillance period was 55 (12
      99) months. The colonoscopic surveillance frequency and interval were similar
      between the two groups. RESULTS: Mean age was higher and male was more frequent
      in SA-group than NSA-group (p= 0.0001). The incidence of missed adenoma, advanced
      missed adenoma and metachronous adenoma (MA) were higher in SA-group (30.8% vs.
      5.8% at 1st yr., p=0.0001; 4.4% vs. 0%, p=0.0001; 31.1% vs. 9.1% at 2nd yr.,
      p=0.016) during the first consecutive two years of surveillance. The MA- and
      advanced-MA-free survival rate were lower in SA-group (24.6% vs. 6.6%, p=0.0001;
      4.1% vs. 0%, p=0.02) during three years after surgery. Dysplasia of the SA
      (p=0.04; OR, 110.3; 95% CI, 1.13-10742.6) and presence of missed adenoma
      (p=0.036; OR, 43.6; 95% CI, 1.28-1490.1) were risk factors for the advanced MA on
      a multivariate analysis in SA-group. CONCLUSIONS: Postoperative colonoscopic
      surveillance at first year after surgery is warranted in CRC patients with SA.

PMID- 16301853
TI  - [Effects of tamoxifen on the voltage-dependent ionic currents in mouse colonic
      smooth muscle cells].
AB  - BACKGROUND/AIMS: Tamoxifen is a widely used anticancer drug for breast cancer
      with frequent gastrointestinal side effects. Changes in gastrointestinal motility
      is associated with altered activities of membrane ion channels. Ion channels have
      important role in regulating membrane potential and cell excitability. This study
      was performed to investigate the effects of tamoxifen on the membrane ionic
      currents in colonic smooth muscle cells. METHODS: Murine colonic smooth muscle
      cells were isolated from the proximal colon using collagenase, and the membrane
      currents were recorded using a whole-cell patch clamp technique. RESULTS: Two
      types of voltage-dependent K(+) currents were recorded (A-type and delayed
      rectifier K(+) currents). Tamoxifen inhibited both types of voltage-dependent
      K(+) currents in a dose-dependent manner. However, tamoxifen did not change the
      half-inactivation potential and the recovery time of voltage-dependent K(+)
      currents. Chelerythrine, a protein kinase C inhibitor or phorbol 12, 13
      dibutyrate, a protein kinase C activator did not affect the voltage-dependent
      K(+) currents. Guanosine 5'-O-(2-thio-diphosphate) did not affect the tamoxifen
      induced inhibition of voltage-dependent K(+) currents. Tamoxifen inhibited
      voltage-dependent Ca(2+) currents completely in whole-test ranges. CONCLUSIONS:
      These results suggest that tamoxifen can alter various membrane ionic currents in
      smooth muscle cells and cause some adverse effects on the gastrointestinal
      motility.

PMID- 16301854
TI  - [Disintegration of pancreatic duct stones with extracorporeal shockwave
      lithotripsy].
AB  - BACKGROUND/AIMS: Treatment of pancreatic duct stones by extracorporeal shockwave
      lithotripsy (ESWL) serves as a nonsurgical treatment modality in patients with
      stones that are located in upstream of the strictures or in patients with
      impacted stones. We present the results of ESWL in endoscopically unretrievable
      pancreatic duct stones in the past 2 years. METHODS: Between January 2002 and
      December 2003, 58 patients with chronic pancreatitis were treated by ESWL for
      pancreatic duct stones. ESWL was performed with an electrohydraulic lithotripter
      ultrasound focusing system. RESULTS: The mean number of shockwave treatments was
      2.5, and the patients received 4,578 (1,527-10,155) shockwave discharges with a
      mean energy of 15.8 kV. Fragmentations of the stones were achieved in 54 patients
      (93.2%), and complete clearance of the stones were noticed in 27 patients
      (46.6%). Fragmentation of stones equal or less than 3 mm in diameter was
      associated with successful removal of stones (p<0.05). Complete relief of pain
      occurred in 32 patients (55.2%). The procedures were well tolerated and no
      patient had significant complications such as acute pancreatitis. CONCLUSIONS:
      ESWL is an effective and a safe procedure for endoscopically unretrievable main
      pancreatic duct stones. ESWL combined with endoscopic therapy can increase the
      success rate of nonsurgical removal of pancreatic duct stones in patients with
      chronic pancreatitis.

PMID- 16301855
TI  - [A case of primary angiosarcoma of small intestine presenting as recurrent
      gastrointestinal bleeding].
AB  - Angiosarcoma is a rare malignant tumor which occurs frequently in the skin and
      soft subcutis. Moreover, primary gastrointestinal angiosarcomas are very rare.
      This tumor manifests as non-specific symptoms such as gastrointestinal bleeding,
      abdominal pain and nausea. The diagnosis is often made at an advanced stage.
      Surgery, chemotherapy and radiotherapy are the mainstay of treatment. However,
      the prognosis is very poor. We report a case of primary angiosarcoma of the small
      intestine presenting as recurrent gastrointestinal bleeding. A 54-year-old man
      was admitted with recurrent gastrointestinal bleeding. An abdominal CT scan
      revealed an ileo-ileal intussusception. Segmental resection was performed with
      ileo-ileal anastomosis. The ileal mass was diagnosed as angiosarcoma on
      immunohistochemical stain. He received 3 cycles of chemotherapy, but died 5
      months after the diagnosis.

PMID- 16301856
TI  - [A case of metastasis-induced acute pancreatitis improved by chemotherapy].
AB  - Pancreatic metastases are found in up to 40% of patients with small cell lung
      cancer, but metastasis-induced acute pancreatitis is rare. Treatment of
      metastasis-induced acute pancreatitis is initially supportive, but failure of
      conservative management are common. There are few reports on aggressive treatment
      with chemotherapy which lead to rapid clinical improvement and prolongation of
      survival in patients with metastasis-induced acute pancreatitis. We experienced a
      case of metastasis-induced acute pancreatitis in a patient with small cell lung
      cancer. Despite conservative treatment with dietary restriction and intravenous
      fluid supply, serum amylase levels increased persistently with severe abdominal
      pain. After chemotherapy with irinotecan and carboplatin, abdominal pain and
      serum amylase levels resolved dramatically.

PMID- 16301857
TI  - [Endoscopic injection treatment for gastric dieulafoy lesion in two newborn
      infants].
AB  - Dieulafoy lesion is an abnormally large calibered submucosal artery associated
      with a minute mucosal defect in the gastrointestinal mucosa. It is a rare cause
      of profuse, but intermittent gastrointestinal bleeding. The lesion is usually
      located in the stomach, although it may occur anywhere in the gastrointestinal
      tract. Dieulafoy lesion is extremely rare in the neonates. We report two newborn
      infants with a gastric Dieulafoy lesion which was treated by endoscopic
      epinephrine injection therapy without complication and recurrence.

PMID- 16301858
TI  - [Role of extracorporeal shockwave lithotripsy for the treatment of pancreatic
      duct stone].

PMID- 16301860
TI  - Genetic variation associated with preterm birth: a HuGE review.
AB  - Preterm birth (PTB) is a major public health concern because of its high
      prevalence, associated mortality and morbidity, and expense from both short-term
      hospitalization and long-term disability. In 2002, 11.9% of U.S. births occurred
      before 37 weeks gestation. Epidemiologic studies have identified many
      demographic, behavioral, and medical characteristics associated with PTB risk. In
      addition, recent evidence indicates a role for genetic susceptibility. We
      reviewed 18 studies published before June 1, 2004, that examined associations
      between polymorphisms in the maternal or fetal genome and PTB risk. Studies of a
      polymorphism in tumor necrosis factor-alpha, a proinflammatory cytokine, showed
      the most consistent increase in the risk of PTB. Environmental factors such as
      infection, stress, and obesity, which activate inflammatory pathways, have been
      associated with PTB, suggesting that environmental and genetic risk factors might
      operate and interact through related pathways. This review highlights maternal
      and fetal genetic susceptibilities to PTB, the potential relationships with
      environmental risk factors, and the need for additional well-designed studies of
      this critical public health problem.

PMID- 16301861
TI  - Deficiency of knowledge of genetics and genetic tests among general
      practitioners, gynecologists, and pediatricians: a global problem.
AB  - PURPOSE: The objective of this study was to assess knowledge of genetics and
      awareness of genetic tests among Dutch general practitioners (GPs), gynecologists
      (GYNs), and pediatricians (PEDs), as well as factors influencing their knowledge
      and awareness. METHODS: An anonymous questionnaire inquiry was used, validated
      with a sample of 52 clinical geneticists (CGs). The study was carried out in
      primary care (general practice) and secondary care (general and university
      hospitals) in The Netherlands. A random sample of 200 GPs, 300 GYNs, and 265 PEDs
      received a questionnaire. In addition, all registered CGs (58) received a
      questionnaire for validation. In total, 122 GPs, 187 GYNs, 164 PEDs, and 52 CGs
      returned a completed questionnaire. The main outcome measures were differences in
      knowledge scores between physicians working in different disciplines and factors
      influencing these scores. RESULTS: Knowledge scores of GPs (mean 64% correct
      answers, 61%-66% [95% confidence interval]), GYNs (mean 75% correct answers, 73%
      76% [95% confidence interval]), and PEDs (mean 81% correct answers, 79%-82% [95%
      confidence interval]) were lower than those in the CG validation group (mean 95%
      correct answers, 94%-96% [95% confidence interval]). The 5th percentile of GPs,
      GYNs, and PEDs was at approximately 40%, 52% and 62% correct answers,
      respectively. There was a specific lack of knowledge about DNA testing. In
      addition to specialty, important factors positively associated with the knowledge
      scores of nongeneticists are more recent graduation, having taken an elective
      course in genetics, and providing genetic counseling in their own practice.
      CONCLUSION: The overall knowledge levels of genetics in many nongeneticist health
      care providers show clear deficiencies. This is in line with reports from other
      countries, showing that these deficiencies are a global problem.

PMID- 16301862
TI  - Clinical testing for the nevoid basal cell carcinoma syndrome in a DNA diagnostic
      laboratory.
AB  - PURPOSE: This study determines which clinical features predict positive test
      results among samples submitted for DNA-based diagnostic nevoid basal cell
      carcinoma syndrome (NBCCS) testing, and further defines the mutational spectrum
      of the PTCH gene. METHODS: DNA was extracted from peripheral blood leukocytes,
      and polymerase chain reaction products from exons 1 to 23 of the PTCH gene were
      directly sequenced. Pedigree phenotypic information was obtained by written
      questionnaire. RESULTS: Among 106 presumably unrelated pedigrees, 44 independent
      mutations were found in 47 families. There were 11 nonsense mutations; 1 in-frame
      deletion; 17 deletions, 6 insertions, and 1 deletion-insertion that generated
      frameshifts; 5 splice-site mutations; 1 in-frame duplication; and 2 presumptive
      missense mutations. Twenty-seven of 46 pedigrees (58.7%) with two or more typical
      radiographic or pathologic features of NBCCS tested positive for PTCH mutations.
      Of these, 26 had jaw cysts in combination with other characteristics or neoplasms
      including basal cell carcinomas, palmar pits, skeletal abnormalities, ocular
      abnormalities, medulloblastomas, cardiac or ovarian fibromas, calcification of
      the falx cerebri, polydactyly, cleft lip and/or palate, and agenesis of the
      corpus callosum or other central nervous system malformations. None of the 13
      pedigrees solely affected by multiple or early-onset basal cell carcinomas and
      none of the four pedigrees with jaw cysts alone had PTCH mutations. CONCLUSIONS:
      Pedigrees with multiple features of NBCCS were most likely to test positive for
      PTCH mutations. Pedigrees with multiple or early-onset basal cell carcinomas
      without other features of the disease did not test positive for PTCH mutations.

PMID- 16301863
TI  - Cytogenetic and molecular evaluation of 241 small supernumerary marker
      chromosomes: cooperative study of 19 Italian laboratories.
AB  - PURPOSE: We evaluated the experiences of 19 Italian laboratories concerning 241
      small supernumerary marker chromosomes (sSMCs) with the aim of answering
      questions arising from their origin from any chromosome, their variable size and
      genetic content, and their impact on the carrier's phenotype. METHODS:
      Conventional protocols were used to set up the cultures and chromosome
      preparations. Both commercial and homemade probes were used for the fluorescent
      in situ hybridization analyses. RESULTS: A total of 113 of the 241 sSMCs were
      detected antenatally, and 128 were detected postnatally. There were 52 inherited
      and 172 de novo cases. Abnormal phenotype was present in 137 cases (57%), 38 of
      which were antenatally diagnosed. A mosaic condition was observed in 87 cases
      (36%). In terms of morphology, monocentric and dicentric bisatellited marker
      chromosomes were the most common, followed by monocentric rings and short-arm
      isochromosomes. The chromosomes generating the sSMCs were acrocentric in 132
      cases (69%) and non-acrocentric chromosomes in 60 cases (31%); a neocentromere
      was hypothesized in three cases involving chromosomes 6, 8, and 15. CONCLUSION:
      The presented and published data still do not allow any definite conclusions to
      be drawn concerning karyotype-phenotype correlations. Only concerted efforts to
      characterize molecularly the sSMCs associated or not with a clinical phenotype
      can yield results suitable for addressing karyotype-phenotype correlations in
      support of genetic counseling.

PMID- 16301864
TI  - Tay Sachs disease carrier screening in schools: educational alternatives and
      cheekbrush sampling.
AB  - PURPOSE: Tay Sachs disease carrier screening programs have been offered
      successfully worldwide since 1970. The programs typically offer education,
      testing, and counseling to provide reproductive choices. One such program has
      been offered to Jewish school students in Melbourne since 1998. In a time of
      increasing public awareness of genetics, programs require continuous evaluation
      and updating. METHODS: Over 2 successive years, a longitudinal evaluation
      involved students attending Jewish schools in Melbourne. Both qualitative and
      quantitative techniques were used to analyze alternative methods for education
      and sampling procedures. Comparisons involved (1) a computer-based resource
      versus an oral educational presentation and (2) blood sampling for enzyme and
      genetic testing versus cheekbrush testing for genetic sampling alone. RESULTS:
      The education session was effective in significantly increasing students'
      knowledge (10.5% +/- 1.2%, P < .0001) and decreasing their anxiety about being a
      carrier (-12.2% +/- 1.6%, P < .0001). For the students, no significant
      differences were found between the computer-based resource and oral presentation.
      There were significantly more students accepting a carrier test and anxiety was
      lower when a cheekbrush test was offered compared with when a blood test was
      offered. CONCLUSIONS: Computer-based instruction is equally effective, in
      addition to offering advantages of self-paced learning and minimization of human
      resources as an oral presentation within a genetic carrier screening program.
      Cheekbrush sampling is preferred to blood sampling and should be implemented into
      current practices for offering genetic screening programs. These results present
      alternatives to practices for genetic screening reflecting the current developing
      technology.

PMID- 16301865
TI  - Technical validation of a multiplex platform to detect thirty mutations in eight
      genetic diseases prevalent in individuals of Ashkenazi Jewish descent.
AB  - PURPOSE: This study determines the analytic accuracy of a Luminex bead-based
      commercial analyte-specific reagent for the simultaneous analysis of 30 mutations
      prevalent in Ashkenazi Jews at eight genetic disease loci. METHODS: DNA from 20
      samples with known abnormal genotypes were run a total of 109 times. DNA from 820
      patients with unknown genotypes submitted for Ashkenazi Jewish testing panels
      were analyzed using our current laboratory techniques. The 820 samples were then
      stripped of identifiers, coded, and reanalyzed using the Tm Biosciences (Toronto,
      Canada) Ashkenazi Jewish panel analyte-specific reagent in a blinded fashion. For
      the controls, comparisons were made with their known genotypes. For the patient
      samples, the results of the Tm assay were compared with the results of our
      current assay. For 24 of the 30 mutations, we had genomic DNA controls or
      detected patients' samples heterozygous for these mutations. RESULTS: There were
      no discrepant results in the control or patient samples. In the patient samples,
      19,680 genotyping reactions were performed without error in both our laboratory
      developed single-disease assays and the Tm multiplex assay. Including the
      controls, 22,296 genotypes were determined without error. CONCLUSION: The Tm
      Biosciences Ashkenazi Jewish analyte-specific reagent is capable of performing
      accurate analyses of 24 different mutations in eight different genes in a single
      multiplex reaction and can be used with confidence in the clinical molecular
      genetics laboratory.

PMID- 16301866
TI  - Association between screening family medical history in general medical care and
      lower burden of cancer worry among women with a close family history of breast
      cancer.
AB  - PURPOSE: Soliciting family medical history (FMH) is the initial step in the
      process of screening for heritable cancer risk in medical care. We investigate
      whether recent solicitation of FMH in general medical care is associated with
      cancer worry among a sample of women having a first-degree relative with a breast
      cancer diagnosis. METHODS: Surveys were mailed to women registered with the
      Cancer Genetics Network having a first-degree relative with a breast cancer
      diagnosis and a regular source of medical care. The independent measure consisted
      of two items for solicitation of FMH based on validated measures of clinical
      interactions with one's physician; the dependent measure was a novel measure of
      cancer worry based on validated patient-centered measure of distress; and the
      secondary measures were 6-point scales for perceived likelihood of developing
      breast cancer and perceived severity of breast cancer as a health outcome.
      RESULTS: A total of 353 women responded and met eligibility criteria (76.4%
      minimum response rate). One fifth reported no cancer worry during the past 4
      weeks. After adjustment for age, education, pedigree features, and clustering
      within families, recent FMH solicitation was associated with lower odds of cancer
      worry (odds ratio = 0.58; 95% confidence interval = 0.51-0.70). FMH solicitation
      was associated with lower perceptions of the severity of developing breast cancer
      but not with the perception of cancer likelihood. CONCLUSIONS: Our data do not
      support the hypothesis that FMH solicitation in general medical practice causes
      cancer worry. In fact, we observed a protective association possibly explained by
      influences on perceptions of breast cancer severity. Prospective research among
      less select populations is necessary.

PMID- 16301867
TI  - The molecular basis of UDP-galactose-4-epimerase (GALE) deficiency galactosemia
      in Korean patients.
AB  - PURPOSE: UDP-galactose-4-epimerase (GALE) deficiency galactosemia is an autosomal
      recessive disorder and the prevalence of the disease varies among ethnic groups.
      We aimed to investigate molecular characteristics of the Korean patients with
      attenuated GALE activity and elevated galactose-1-phosphate levels in blood.
      METHODS: In order to characterize the molecular defects underlying GALE
      deficiency, the GALE gene of 7 patients showing severe activity decreases was
      sequenced. PCR-RFLP was performed to confirm the presence of the mutations
      identified by sequencing. RESULTS: Nine mutations were identified: 8 missense
      mutations (p.A25V, p.R40C, p.D69E, p.E165K, p.R169W, p.R239W, p.G302D, and
      p.R335H) and one nonsense mutation (p.W336X). Except for p.R335H, all of these
      mutations are novel. Six patients were compound heterozygotes (p.D69E/p.G302D,
      p.R40C/p.R169W, p.D69E/p.E165K, p.R239W/p.R335H, p.A25V/p.R169W, and
      p.G302D/p.R335H) and the remaining patient had only one mutation (p.W336X/not
      detected). Thirty patients with moderately reduced GALE activity were also tested
      by PCR-RFLP for the presence of the above mutation, and mutations were detected
      in 17 of these 30 patients. The frequency of p.G302D (9/30), p.R239W (6/30) and
      p.R169W (5/30) in our Korean patients with GALE deficiency galactosemia was
      relatively high. CONCLUSIONS: We detected 9 mutations of the GALE gene in Korean
      galactosemia patients, and confirmed allelic heterogeneity in this disease.

PMID- 16301869
TI  - Sporadic breast cancer among relatives of BRCA mutation carriers.

PMID- 16301868
TI  - American College of Medical Genetics guideline on the cytogenetic evaluation of
      the individual with developmental delay or mental retardation.
AB  - DISCLAIMER: This guideline is designed primarily as an educational resource for
      medical geneticists and other health care providers to help them provide quality
      medical genetic services. Adherence to this guideline does not necessarily assure
      a successful medical outcome. This guideline should not be considered inclusive
      of all proper procedures and tests or exclusive of other procedures and tests
      that are reasonably directed to obtaining the same results. In determining the
      propriety of any specific procedure or test, the geneticist should apply his or
      her own professional judgment to the specific clinical circumstances presented by
      the individual patient or specimen. It may be prudent, however, to document in
      the patient's record the rationale for any significant deviation from this
      guideline.

PMID- 16301870
TI  - Should the MTHFR 1298A>C polymorphism be considered in the clinical evaluation of
      patients at risk for thrombotic disease?

PMID- 16301875
TI  - A family member's experience with ECT.

PMID- 16301876
TI  - Grateful for grateful parents.

PMID- 16301877
TI  - Atropine coma: a historical note.
AB  - Insulin coma and various types of convulsive therapies were the major biologic
      treatment modalities in psychiatry before the psychopharmacological era. Except
      for electroconvulsive therapy (ECT), these methods disappeared from the
      psychiatric armamentarium after the introduction of psychotropic drugs. Atropine
      coma therapy (ACT) was one variety of nonconvulsive coma therapy used from the
      1950s in a few state mental hospitals in the United States and in several Middle-
      and Eastern European countries until the late 1970s. In ACT, a coma of 6-10
      hours' duration was induced with doses of parenteral atropine sulfate that were
      hundreds of times greater than the therapeutic dose administered in internal
      medicine. Although ACT was given to thousands of patients with a variety of
      diagnoses for nearly 3 decades, it is rarely mentioned, even in papers on the
      history of psychiatry. The method, indications, contraindications and adverse
      effects of ACT are summarized together with patients' personal accounts.
      Hypotheses concerning its mode of action are briefly mentioned. The reasons why
      ACT never gained wider acceptance are explored in the context of both
      contemporary psychiatric practice and the broader sociocultural climate of the
      era.

PMID- 16301878
TI  - Bifrontal versus right unilateral and bitemporal electroconvulsive therapy in
      major depressive disorder.
AB  - OBJECTIVES: We sought to evaluate the safety and efficacy of three
      electroconvulsive therapy (ECT) methods: moderate-dose bifrontal, low-dose
      bitemporal, and high-dose right unilateral in the treatment of a major depressive
      episode. METHODS: In an 8-session, double-blinded parallel group study, 45
      consecutive depressive patients who were referred for ECT to Noor Hospital were
      assigned randomly to bifrontal, moderate dose (50% above seizure threshold; n =
      15); bitemporal, low dose (just above seizure threshold; n = 15); and right
      unilateral, high dose (400% above the seizure threshold; n = 15) ECT
      applications. Primary outcome measures included assessment by Mini-Mental State
      Examination and Hamilton Depression Rating Scale. RESULTS: Thirty-nine of the
      patients completed the course of treatment. Two patients in bifrontal, 1 in
      bitemporal, and 3 in right unilateral dropped out of the study. The 3 groups did
      not show any difference in baseline characteristics. There was a significant
      difference between standardized Mini-Mental State scores of patients in bifrontal
      group compared with bitemporal and right unilateral patients (P < 0.05). The
      effectiveness of the 3 ECT methods, assessed by Hamilton Depression Rating Scale,
      did not show any significant difference (P > 0.05). CONCLUSION: Moderate-dose
      bifrontal ECT revealed fewer cognitive side effects in comparison with bitemporal
      and right unilateral. Moderate-dose bifrontal ECT had the same efficacy compared
      with low-dose bitemporal and high-dose right unilateral in the treatment of
      depression.

PMID- 16301879
TI  - What do psychiatrists mean by medication resistance as an indication for
      electroconvulsive therapy?
AB  - OBJECTIVES: Resistance to antidepressant medication is the commonest stated
      indication for electroconvulsive therapy (ECT) by psychiatrists, but what this
      means in practice has not been described. Our aims were to survey what
      antidepressant drug treatment had been prescribed to patients before they
      underwent ECT and to what extent this treatment would satisfy operational
      criteria for adequate antidepressant drug treatment used in ECT research.
      METHODS: The survey was conducted prospectively among 37 depressed patients
      referred for a new course of bilateral ECT and where antidepressant medication
      resistant was identified as the indication for ECT. RESULTS: Only half the sample
      had been prescribed more than one antidepressant drug, and only 38% had been
      prescribed any augmentation compound. Although the majority of patients were
      resistant to medication when rated by the older operational criteria, only half
      the sample met contemporary criteria for medication resistance. CONCLUSIONS: The
      findings suggest a lack of agreement between clinicians and researchers in what
      constitutes medication resistance as a possible indication for ECT. It will take
      some time to establish if the revised UK Royal College of Psychiatrists ECT
      Handbook will encourage more intensive medical treatment of depressive illness
      before the use of ECT.

PMID- 16301880
TI  - Long-term follow-up in depressed patients treated with electroconvulsive therapy.
AB  - DESIGN: Our aim was to study the long-term effects of electroconvulsive therapy
      (ECT) in depression. A total of 55 patients were followed-up 20 to 24 years after
      an ECT series; 13 patients were still alive, and 10 agreed to participate in the
      study. All 55 patients had been investigated with clinical and neuropsychological
      assessment and with neurophysiological measurements and with regional cerebral
      blood flow (rCBF) and EEG before the first ECT, 6 months later, and after
      approximately 1 year. These investigations were repeated in the 10 patients.
      RESULTS: Before the original ECT series, all patients had suffered from severe
      mood disorder. At follow-up, the 10 patients showed no clear signs of mood
      disorder or cognitive impairment. There was a slightly subnormal performance in
      working memory and in verbal as well as visual episodic memory on all 3 occasions
      after the ECT series. The rCBF measurement showed a significant average CBF
      decrease from the first to the last measurement. There was, moreover, a
      significant rCBF decrease in frontal areas at the last measurement compared with
      the 3 previous assessments. CONCLUSION: All ten patients followed-up 20 to 24
      years after an ECT series were mentally healthy and thus besides a moderate
      visual memory dysfunction, no severe side effects were observed with clinical and
      neuroimaging techniques.

PMID- 16301881
TI  - One-year outcome of psychotic depression after successful electroconvulsive
      therapy.
AB  - BACKGROUND: Psychotic depression is thought to have a higher relapse frequency
      after electroconvulsive therapy (ECT) compared with nonpsychotic depression,
      although this observation is contradicted by previous studies that have found the
      opposite. In this study, the 1-year risk of relapse after successful ECT was
      determined prospectively in patients with psychotic depression and compared with
      the risk of relapse observed for depressed patients without psychotic features.
      METHOD: Fifty-nine responders to ECT (a decrease in Hamilton Rating Scale for
      Depression [HAM-D] score > or = 50%) were followed for 1 year: 29 with and 30
      without psychotic features. Relapse was defined as meeting DSM-IV criteria for
      major depressive disorder and a HAM-D score > or = 16. The frequency of relapse
      after 4 and 12 months was compared between both samples, adjusted for the co
      variables duration of the index episode and type of post-ECT pharmacotherapy.
      RESULTS: : At both 4 and 12 months after ECT, instances of relapse were
      significantly lower in patients with psychotic depression compared with
      nonpsychotic patients: 3/28 (11%) versus 16/27 (59%) and 4/27 (15%) versus 19/28
      (68%), respectively. CONCLUSIONS: The main finding of the present study is the
      favorable 1-year outcome for patients with psychotic depression after response to
      ECT with a trend toward the same result at 4 months. The 1-year outcome of the
      total sample is also more favorable than expected.

PMID- 16301882
TI  - Patient satisfaction after electroconvulsive therapy.
AB  - OBJECTIVE: We sought to determine the degree of satisfaction with bifrontal and
      right unilateral electroconvulsive therapy (ECT) and to investigate the relation
      with treatment-related variables, such as memory complaints, and patient-related
      variables, such as self-rated depression severity and negative affectivity.
      METHODS: Subjects included all patients who started a course of ECT between May
      2001 and December 2003, or still were receiving continuation or maintenance ECT
      (C/M-ECT) at the time of the study. A psychiatric nurse that was not a member of
      the treatment team conducted semi-structured interviews based on a battery of
      questionnaires (Patient Satisfaction Survey [PSS], Mini-Mental State Examination
      [MMSE], Squire Subjective Memory Questionnaire [SSMQ], Beck Depression Inventory
      [BDI], and Positive and Negative Affect Schedule [PANAS]). RESULTS: Of 50
      eligible subjects, 36 (72%) completed the survey. Fourteen patients refused to
      participate. At the time of the interview, 19 patients (52.8%) were hospitalized,
      and 14 (38.9%) were receiving C/M-ECT. The mean time between last treatment
      session and interview was 282 days. Diagnostic categories were depressive
      disorder (50%) and psychotic disorder (47.2%). Bifrontal electrode position was
      used in 25 (69.4%) of the study patients and unilateral in 4 (11.1%). Patients
      had a considerable degree of satisfaction (mean PSS 153.41; SD 16.29), although
      they had prominent cognitive complaints (mean score SSMQ -11.86; SD 21.30). In a
      multiple regression model, in which satisfaction was predicted on the basis of
      age, sex, and scores on BDI, SSMQ, PANAS, and GAF, only the GAF-score at the time
      of the interview was significantly related to satisfaction. All other predictors
      were not significant. CONCLUSION: Patients receiving bifrontal or right
      unilateral ECT do have considerable memory complaints, even a long time after
      their treatment. However, the degree of these complaints does not seem to predict
      satisfaction with the treatment. Only 38% of the variance of satisfaction could
      be predicted on the basis of age, sex, BDI, SSMQ, Negative Affectivity subscale
      of the PANAS, and GAF-scores, which proves that satisfaction with ECT is based on
      other factors than just the relief of symptoms or the occurrence of side-effects.
      The factors that contribute to patients' satisfaction remain largely unknown.

PMID- 16301883
TI  - The effect of electroconvulsive therapy treatments on blood sugar in nondiabetic
      patients.
AB  - There are conflicting data in the literature about the effects of
      electroconvulsive therapy (ECT) on blood sugar. In general, glycemic control and
      insulin requirements show no changes over a course of treatments, although there
      is interindividual variation. What is understudied is the acute effect of single
      ECT treatments on blood sugar in the post-ictal time period. To shed more light
      on this issue, we conducted a simple study of blood sugar assessed by fingerstick
      before and 20 minutes after ECT treatments in 33 nondiabetic patients. There was
      a small though statistically significant rise of 9 mg/dL in blood glucose after
      ECT treatments, without effect of age or gender. We conclude that ECT does not
      have a clinically significant effect on blood sugar in non-diabetic patients.

PMID- 16301884
TI  - Remifentanil supplementation of propofol during electroconvulsive therapy: effect
      on seizure duration and cardiovascular stability.
AB  - OBJECTIVES: Electroconvulsive therapy (ECT) is standard treatment of severe
      depression. The induction of a seizure is a core event in successful ECT.
      Although propofol is a frequently used anesthetic agent, one of its limitations
      is a reduction of seizure duration. No such effects have been reported regarding
      remifentanil, an ultrarapid-acting opioid that is used to induce and maintain
      anesthesia. The simultaneous administration of propofol and remifentanil may have
      similar safety and efficacy in terms of induction of anesthesia during ECT as
      propofol alone and significantly increase seizure duration. METHODS: Twenty-one
      ECT patients (10 men, 11 women, aged 24 to 81 years) were recruited. Muscle
      paralysis was achieved with succinylcholine (0.5-0.75 mg/kg intravenously [IV]).
      Unconsciousness was induced by either propofol (1 mg/kg IV) or propofol (0.5
      mg/kg IV) + remifentanil (1 microg/kg) in a crossover format. ECT was
      administered according to established clinical protocols at the Sheba Medical
      Center, Israel. No changes in ECT current were permitted in the 2 protocols of
      each patient. Statistical analysis was based on paired t tests. RESULTS: In all
      but 2 cases, seizure duration was significantly longer in the remifentanil group
      than in the control group (motor seizure 53.7 +/- 28.3 seconds vs. 29.5 +/- 10.9
      seconds, t = 4.017, P = 0.0007; Electroencephalographic (EEG) seizures 60.8 +/-
      25.1 seconds vs. 40.1 +/- 17.0 seconds, t = 3.971, P = 0.001). No significant
      differences were found in mean recovery time, post-treatment elevation in blood
      pressure, heart-beat, or oxygen saturation. CONCLUSION: During anesthesia, the
      addition of remifentanil to propofol appears to be as effective as propofol alone
      with regard to anesthesia efficacy and cardiovascular function while
      significantly increasing seizure duration. Whether this discovery is of relevance
      to the clinical efficacy of ECT remains to be tested.

PMID- 16301885
TI  - The clinical utility of inhalational anesthesia with sevoflurane in
      electroconvulsive therapy.
AB  - Anesthesia in electroconvulsive therapy (ECT) almost always is induced with
      intravenous agents, typically barbiturates, etomidate, or propofol. There are,
      however, circumstances in which an inhalational agent would be preferable for
      induction of general anesthesia. These uncommon clinical scenarios include severe
      needle stick phobia, agitation preventing insertion of an intravenous catheter,
      and poor tolerance of intravenous induction agents. Among the inhalational agents
      available, sevoflurane has several properties that make it the most desirable. In
      this case series, we describe several patients in our ECT practice in whom
      inhalational induction of general anesthesia with sevoflurane was deemed
      appropriate. In all patients, this method was well tolerated and offered distinct
      advantages compared with an intravenous induction agent. We conclude that ECT
      practitioners should keep this option in mind for select patients.

PMID- 16301886
TI  - Motor cortical excitability in depressive patients after electroconvulsive
      therapy and repetitive transcranial magnetic stimulation.
AB  - Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation
      (rTMS) of the dorsolateral prefrontal cortex are brain stimulation techniques
      that are used as therapeutic interventions in major depression. However, the
      exact therapeutic mode of action needs further clarification. In this case
      report, we describe the impact of these stimulation techniques on motor cortical
      excitability, as revealed by transcranial magnetic stimulation-elicited motor
      evoked potentials in 2 patients who received consecutively both rTMS and ECT.
      Both patients showed a decrease in motor cortical excitability after response to
      antidepressant brain stimulation, whereas parameters of motor cortical
      excitability remained unchanged after the first non-successful intervention.
      These results suggest that both ECT and rTMS may have an impact on parameters of
      motor cortical neuronal excitability. Furthermore, measurement of motor cortical
      excitability may be a useful tool for investigating and monitoring inhibitory
      brain effects of different antidepressant stimulation techniques.

PMID- 16301887
TI  - Gilles de la Tourette syndrome: response to electroconvulsive therapy.
AB  - Tourette syndrome is a chronic disease characterized by vocal and motor ticks.
      Self-injurious behavior is observed in one third of the patients and can be life
      threatening. Current medical therapy includes dopamine receptor antagonists and
      atypical antipsychotics. In certain cases, there has been some evidence about the
      efficacy of electroconvulsive therapy (ECT). The case study below is a Tourette
      syndrome patient with self-injurious behavior and psychotic features and poor
      response to medical therapy. Two years of remission was achieved after 7 sessions
      of ECT and carbamezapine maintance therapy. In conclusion, ECT can be used as an
      efficacious treatment modality for Tourette patients with self-injurious
      behavior, psychotic features, or for those that are unresponsive to traditional
      methods.

PMID- 16301888
TI  - Supraorbital edema induced by electroconvulsive therapy.
AB  - This is a case report of an unusual side effect-unilateral supraorbital edema
      occurring immediately after electroconvulsive therapy ECT during each treatment
      occasion-in a depressed patient who was otherwise well. The affected upper eyelid
      appeared normal before ECT with no history of injury or abnormality. Trauma
      during ECT, allergic reaction to anesthetic agents, and complications of manual
      ventilation were found to be unlikely causes. The supraorbital edema occurred as
      an isolated, benign, complication of ECT and resolved spontaneously.

PMID- 16301889
TI  - Successful use of continuation electroconvulsive therapy in a case of late-onset
      Leonhard's confusion psychosis.
AB  - A 56-year-old married woman with late-onset Leonhard's confusion psychosis was
      treated successfully with acute electroconvulsive therapy (ECT) after failing to
      respond to antidepressants, neuroleptics, and benzodiazepines. Symptoms relapsed
      within 1 year despite the combined use of olanzapine and paroxetine. The patient
      responded to a second course of acute ECT, but a second relapse occurred within 3
      months despite her use of olanzapine and paroxetine. The symptoms resolved with
      continuation ECT and lithium combined with paroxetine after response to a third
      course of acute ECT. To date, relapse has been prevented for 2 years.
      Continuation ECT and lithium combined with paroxetine after response to acute ECT
      may be effective in maintaining remission of Leonhard's confusion psychosis.

PMID- 16301890
TI  - ECT devices in India.

PMID- 16301892
TI  - ECT and aortic aneurysm.

PMID- 16301891
TI  - Unsupported claims of ECT risk.

PMID- 16301893
TI  - Electroconvulsive therapy in organic bipolar disorder with multiple system
      atrophy.

PMID- 16301894
TI  - Knowledge about and attitudes towards ECT: methodological issues.

PMID- 16301896
TI  - The bed bath.

PMID- 16301897
TI  - WCET and WOCN: what is the difference?

PMID- 16301898
TI  - Budding bariatrics.

PMID- 16301900
TI  - Mechanical bowel preparation before elective colorectal surgery.

PMID- 16301901
TI  - Writing a grant proposal: part 6: the budget, budget justification, and resource
      environment.

PMID- 16301902
TI  - Health-related quality of life in diabetic patients with foot ulcers: literature
      review.
AB  - Foot ulcers are a common, serious, and costly complication of diabetes, preceding
      84% of lower extremity amputations in diabetic patients and increasing the risk
      of death by 2.4-fold over diabetic patients without ulcers. Health-related
      quality of life (HRQOL) is worse among individuals with diabetes than individuals
      without diabetes, and complications of diabetes, including foot ulcers, have a
      major negative effect on HRQOL. Diabetic foot ulcers are associated with reduced
      mobility and deficits related to activities of daily living that adversely affect
      HRQOL. Qualitative studies have confirmed clinical observations that diabetic
      foot ulcers have a huge negative psychological and social effect, including
      reduction in social activities, increased family tensions for patients and their
      caregivers (spouses or partners), limited employment, and financial hardship.
      Quantitative studies confirm the findings of qualitative studies that diabetic
      foot ulcers exert a negative effect on physical functioning, psychological
      status, and social situation. Recent advances include the development and
      validation of disease-specific HRQOL surveys for diabetic patients with foot
      ulcers. Disease-specific surveys may improve the evaluation of HRQOL as a
      function of ulcer healing, the effect of different treatment methods on HRQOL,
      and the relationship between treatment-specific HRQOL, patient compliance, and
      treatment efficacy.

PMID- 16301903
TI  - Care of the obese patient with an ostomy.
AB  - Obesity has become the number one health problem in the United States. The
      patients who is obese and undergoing a surgical procedure that results in the
      formation of fecal or urinary diversion requires advanced skills of a
      multidisciplinary healthcare team. Patients who are obese carry a high risk of
      wound and cardiopulmonary complications and often present a serious challenge in
      terms of stoma creation and management. The purpose of this article is to examine
      the risk factors that face the patient who is obese and undergoing stoma surgery,
      the challenges of stoma creation, and the resultant stoma management problems.

PMID- 16301905
TI  - Current issues and challenges in the management of bariatric patients.
AB  - Morbid obesity is an increasingly common healthcare problem, and providers and
      patients currently face numerous challenges in dealing with this problem
      effectively. Issues addressed in this article include the effect of stigma, the
      need for more evidence regarding effective management options, and the declining
      insurance coverage for bariatric surgery. The role of bariatric surgery in
      effective management of morbid obesity is discussed, along with the effect on and
      possible reasons for declining coverage. A comparison between benefits and
      coverage for bariatric surgery and angioplasty/stent placement is included.

PMID- 16301906
TI  - Surgical treatment for obesity: ensuring success.
AB  - In the United States, obesity has reached epidemic proportions. Serious medical
      complications, impaired quality of life, and premature mortality are all
      associated with obesity. Medical conditions such as type 2 diabetes mellitus,
      hypertension, hyperlipidemia, or sleep apnea can improve or be cured with weight
      loss. Medical treatment programs focused on diet, behavior modification, and/or
      pharmacologic intervention have met with limited long-term success. Although
      surgical treatments for obesity have become popular in recent years, they should
      only be used as a last resort for weight loss. Not all patients can be considered
      appropriate candidates for surgery; therefore, guidelines based on criteria from
      the National Institutes of Health should be used preoperatively to help identify
      suitable persons. Most individuals who opt for weight-loss surgery have usually
      struggled for many years with losing weight and keeping it off, but surgery alone
      will not ensure successful weight loss. Patient education is imperative for long
      term success. Moreover, any such educational regimen should include information
      on diet, vitamin and mineral supplementation, and lifestyle changes, as well as
      expected weight-loss results and improvements in comorbid conditions. Patients
      must be willing to commit to a long-term follow-up program intended to promote
      successful weight loss and weight maintenance and to prevent metabolic and
      nutritional complications.

PMID- 16301907
TI  - Meeting bariatric patient care needs: procedures and protocol development.
AB  - Regardless of whether your facility has an existing surgical bariatric program,
      ongoing attention to staff education and the organization's physical environment
      is key in identifying potential areas of risk and need for improvements in
      meeting the needs of this special patient population. Development of an
      organization-wide protocol specifically designed to meet the needs of all
      bariatric patients will facilitate the provision of safe and dignified care for
      both patient and caregiver. Protocol parameters to include are assessment for
      body mass index, abdominal-hip girth, mobility level, and skin complications.
      Assessment findings trigger care planning for optimal patient outcomes.

PMID- 16301908
TI  - Promoting effective preceptorship experiences.
AB  - Preceptors and students alike want and need a positive preceptorship experience.
      There are some factors, however, that must be considered when arranging such
      experiences, including sufficient time, workload management, use of space,
      monetary payment for preceptorship, preparation for the role, the one-to-one
      relationship, and the learning environment. This article concludes with specific
      strategies that address these factors. The first uses a theoretical model, one
      advocated by the authors, the Preceptor Enabling Model. This model delineates the
      roles and responsibilities of students, preceptors, staff, and faculty.
      Preceptors, too, need preparatory workshops, paid time for orientation to the
      role, evaluation of preceptors, and finally, support.

PMID- 16301909
TI  - Enhancing rigor in qualitative description: a case study.
AB  - Qualitative description has generally been viewed as the "poor cousin" to more
      developed qualitative methods, such as grounded theory. As such, little has been
      written about rigor in qualitative description, and researchers lack a
      navigational map to guide them and facilitate decision making. The novice, in
      particular, can be faced with numerous challenges and uncertainties. Using an
      incontinence project as a case study, the authors describe the issues that arose
      within a qualitative descriptive study and approaches used to maintain rigor. The
      overall credibility of the study depended on the researcher's ability to capture
      an insider (emic) perspective and to represent that perspective accurately.
      Strategies to enhance rigor included flexible yet systematic sampling, ensuring
      participants had the freedom to speak, ensuring accurate transcription and data
      driven coding, and on-going attention to context.

PMID- 16301910
TI  - Venous stasis ulcers in the patient who is obese.

PMID- 16301913
TI  - My journey from there to here.

PMID- 16301916
TI  - Films or fabrics: is it time to re-appraise postoperative dressings?
AB  - Post-operative wounds healing by primary intention are often seen as the simplest
      areas of modern wound care. However, have we overlooked the problems that can
      exist and are we really looking at postoperative dressing selection with the same
      vigour we attach to other areas of wound care? This article outlines the
      development of modern post operative dressings, both fabric and film-based and
      raises the question 'if postoperative wound infection is a problem should we
      consider more effective barrier dressings?'

PMID- 16301917
TI  - The role of silver in wound healing.
AB  - Bacteria present in wounds can have a negative impact on healing, so the increase
      in multi-resistant bacterial strains is a cause of concern for wound care. Silver
      has been demonstrated to have anti-microbial effects and has not as yet been
      shown to suffer from bacterial resistance, so an increasing number of
      manufacturers have launched wound care products utilising silver. A number of
      research studies have examined the effectiveness of silver-based products in
      reducing bacterial burden and treating wound infection. The general conclusion of
      these studies is that silver can be a useful tool in treating infected wounds,
      but the effectiveness of silver-based products is dependent upon the form of
      silver used and the delivery mechanism.

PMID- 16301918
TI  - TVNA goes to Parliament.

PMID- 16301919
TI  - Nutrition and wound healing: the necessity of assessment.
AB  - Wound healing is an intricate affair and good nutritional status is essential to
      promote effective growth and repair of body tissue. Nutrients play vital roles in
      the constitution of a well-balanced diet and any depletion in a person's
      nutritional intake, especially proteins, can lead to malnutrition and protein
      energy malnutrition, conditions which are known to have considerable impact on
      health and well-being and on the wound healing process. A holistic nutritional
      assessment is paramount to the early detection of nutritional deficiency and the
      use of recognized nutritional assessment tools can significantly increase
      practitioners' awareness in its undertaking. While nurses are renowned to have a
      central role in the management of the patient who, nutritionally are at risk, it
      is equally important to remember that overall management is essentially a
      multidisciplinary task.

PMID- 16301920
TI  - Using honey to heal a chronic wound in a patient with epidermolysis bullosa.
AB  - This case study details the healing of a chronic wound (20 years' duration) in a
      patient with dystrophic epidermolysis bullosa (EB). Many different dressings and
      creams had been used, and on occasions the wound began to heal but never
      progressed to closure. A honey impregnated dressing was used and the wound healed
      in 15 weeks. A brief overview of the dystrophic form of EB is given and some
      evidence for the efficacy of honey is presented.

PMID- 16301921
TI  - Keeping sight of the domestic 'flu threat.

PMID- 16301922
TI  - Understanding cachexia and excessive weight loss in cancer.
AB  - Cachexia, a wasting condition often seen in advanced cancer, is often confused
      with anorexia but they are two separate conditions. It is evident that cachexia
      frequently leads to anorexia but anorexia alone cannot cause cachexia. The
      cachexia syndrome is weight loss with a specific cause--the action of cytokines,
      chemical messengers that are produced both by the body in response to the tumour
      and by the tumour to ensure its growth and spread. Treatment of cachexia is very
      difficult. Drugs to improve appetite have little effect, however, supplementing
      the diet with fish oils and vitamin E seems to be beneficial. Increasing a
      patient's level of exercise, even if bed-bound, does seem to have a positive
      effect and helps to synthesize skeletal muscle protein and delay the ravages of
      cachexia. Increasing exercise also has a positive effect on fatigue levels, a
      side-effect of cachexia.

PMID- 16301923
TI  - Exploring district nurses' experience of a hospice at home service.
AB  - Hospice at home (HAH) services complement the role of the district nursing team,
      providing 24-hour palliative home care. However, little is known about district
      nurses' experience or perceptions of working alongside the HAH service. This
      study surveyed a representative sample of district nurses (DNs) to ascertain
      their experience of working alongside an HAH service. A self-completed postal
      questionnaire comprised of 14 items was distributed to 128 DNs. The evaluation
      found significant levels of satisfaction. All respondents indicated that they
      would refer a patient to the service again. However, the need for improved
      communication and increased awareness among DNs about the HAH service were also
      identified. The findings support the idea that an HAH service can enable patients
      with advanced progressive disease to be cared for at home. While the findings of
      this study cannot be generalized, they add to the growing body of research about
      HAH services in palliative care.

PMID- 16301924
TI  - Application of standard precautions in the community setting.
AB  - Healthcare associated infections (HAI) are a major source of morbidity, as well
      as being a significant cause of concern for patients and healthcare workers.
      Nurses have a duty to prevent infection wherever possible. This article provides
      an overview of the standard precautions that all community healthcare workers
      must implement to reduce the incidence of HAI.

PMID- 16301925
TI  - Developing career pathways for new nurses: lessons from inner London.
AB  - Inner city primary care trusts (PCTs) often have difficulty in recruiting nursing
      staff, while newly qualified nurses are often unaware of what opportunities
      community settings offer. This article reports the development of a rotational
      scheme designed to reduce recruitment problems and to assist understanding by
      newly qualified nurses of the interface between hospital and primary care. The
      scheme was jointly run by a PCT, a hospital and an academic unit. Various
      difficulties were encountered, as revealed in an interim evaluation. For example,
      the impression was created among some participating staff nurses and their
      mentors and managers that they had student status, which limited their
      opportunities both to learn and to provide care. The scheme was re-designed in
      the light of the evaluation, and a further evaluation found that participating
      staff nurses appreciated the opportunities the scheme offered, and that their
      work was valued by placement mentors and managers.

PMID- 16301926
TI  - Does compliance therapy improve use of antipsychotic medication?
AB  - Non-compliance with prescribed antipsychotic medication is common among people
      diagnosed with schizophrenia and is associated with high relapse rates.
      Compliance therapy is an intervention to promote compliance, developed from
      motivational interviewing and cognitive behavioural therapy. This mini-review
      aims to examine the evidence for the effect of compliance therapy on promoting
      compliance with antipsychotic medication, compared to usual advice. Online
      medical databases were searched for randomized controlled trials (RCTs) which
      compared a group of participants who received compliance therapy with a group who
      did not. Articles were only considered if the participants were on antipsychotic
      medication; received 4-6 sessions of compliance therapy (as defined by Kemp et al
      (1998)), which lasted 20-60 minutes; and an outcome measure of compliance and
      psychotic symptoms was given. Two RCTs met the inclusion criteria. One reported
      compliance therapy had a significant effect on compliance but not on symptoms.
      The other RCT reported no significant effects from compliance therapy. However,
      methodological flaws effected the validity of both findings. Further quality
      research is required in this important area.

PMID- 16301927
TI  - Self-assessment of health and social care needs by older people: a review.
AB  - This article explores the meaning and significance of 'self-assessment', a term
      that is increasingly being used in relation to developments affecting community
      practice. Self-assessment for health and social care needs has been used over a
      considerable period of time and for purposes as diverse as case finding for
      depression to assessment of housing options. Self-assessment has usually involved
      the use of short scales and questionnaires, but it can involve the use of
      physiological tests (such as testing urine for glucose) or complex, computerized
      decision-support systems. Although often explored as a simple means for extending
      the 'reach' of professional assessments (e.g. mass screening) and ensuring
      'appropriate' use of health services (e.g. self-care algorithms), self-assessment
      is increasingly being advocated as a means of actively involving and empowering
      service users. However, a recent review of the topic (Griffiths et al, 2005)
      revealed the complexity of the topic and the pitfalls of a simplistic approach to
      self-assessment, which those engaged in developing the process should bear in
      mind.

PMID- 16301928
TI  - Advising patients with medication-related dysphagia: caution required.

PMID- 16301929
TI  - Hard choices: what can we afford?

PMID- 16301930
TI  - Spotlight on bereavement services and support.

PMID- 16301931
TI  - The NHS Redress Bill: a rocky road lies ahead.

PMID- 16301932
TI  - Matron of a residential home who failed to manage staff or patients.

PMID- 16301933
TI  - What is a good death? Issues to examine in critical care.
AB  - The decision to limit care for critically ill intensive care patients is not
      uncommon, and most deaths in the intensive care unit are now preceded by do not
      resuscitate (DNR) orders, which are regarded by some as a way to make death more
      humane and respect patient autonomy. When a patient receives a poor diagnosis the
      family needs to discuss the medical care and respect the patient's wishes. Many
      relatives hesitate to discuss these issues, because they wish to avoid discussing
      the idea of death or any serious change to the patient's condition. This article
      aims to address DNR orders and discuss the mechanisms available to achieve a good
      death for patients and their relatives, instead of enduring a distressing and
      undignified end.

PMID- 16301935
TI  - Evolution and healthcare impact of a 21st Century avian flu pandemic.
AB  - The risk of an outbreak of avian flu is greater now than at any time since 1968.
      This article will explore the history of influenza and will discuss the evolution
      and healthcare impact of a 21st Century avian flu pandemic. It highlights the
      need for healthcare professionals to be adequately prepared for such a pandemic
      and discusses the responses and infection control precautions required for
      dealing with avian flu patients.

PMID- 16301934
TI  - An audit of nurses' views on DNR decisions in 1989 and 2003.
AB  - Guidelines on making do not resuscitate (DNR) decisions have changed in recent
      years in keeping with changing attitudes and legislation. Decisions should now be
      discussed with all competent patients, and nursing staff should be involved in
      the process. The views of nursing staff in 1989 and 2003 were compared, focusing
      on what factors they thought were important in coming to a DNR decision and any
      implications it had for other treatment. A patient's wishes, their previous
      quality of life and the chances of successful resuscitation were rated highly in
      both studies. Advanced age was rated as important less often in 2003 but was
      still thought to be an important factor by 61% respondents. In 2003 nurses were
      significantly more likely to state that active treatment, such as admission to an
      intensive care unit or surgical intervention, could be appropriate for patients
      with DNR orders. However, the number of respondents who considered intravenous
      fluids (18%) or antibiotics (26%) inappropriate for patients not for
      resuscitation was concerning.

PMID- 16301936
TI  - The carcinogenic and protective effects of food.
AB  - It has been estimated that 70% of all cancers are caused by the food that we
      consume and smoking tobacco (Wogan et al, 2004). Currently, food health advice
      focuses on maintaining a diet which is low in fat and calories, rather than
      concentrating on the cooking methods used and the amount of meat that is
      consumed. More time should be spent educating individuals on the importance of
      cooking in different ways and eating a varied diet which includes cruciferous
      vegetables, such as broccoli. Nurses can be influential in the provision of
      health education advice to patients on the types of cooking methods that can be
      used to reduce the risk of developing forms of cancer and also the types of food
      that offer protection against cancer.

PMID- 16301937
TI  - Midwifery Records and legal issues surrounding them.
AB  - Midwives are subject to statutory supervision and the Midwives' Rules. The
      Nursing and Midwifery Council has set out very special and very strict rules on
      how midwives records should be kept, stored, handled and supervised. Rule 9 sets
      out stipulations in relation to the keeping of midwifery records. Rule 10
      requires them to permit the inspection of their records by the supervisor, the
      local supervising authority and the NMC.

PMID- 16301938
TI  - Review of homecare packages for paediatric HPN patients.
AB  - This study explored the existing nursing homecare packages required by children
      who receive home parenteral nutrition and their families, in order to evaluate
      the effectiveness of the support required. The study forms the basis for ongoing
      financial discussions with PCTs to ensure high-quality nursing services are
      available and meet the needs of families. Families' views about homecare packages
      developed in response to the needs of care for parenterally fed children were
      explored. Findings indicated three emergent themes that families face: physical,
      psychological and burden of care. Homecare packages developed in response to
      family needs were highlighted as being essential. A 24-hour on-call service with
      expert paediatric nursing staff was a key factor for families to feel secure. It
      was felt that the individualized homecare packages supported the vulnerable
      patient group. Families felt that nursing their child at home was a major
      advantage in the homecare package, but improved delivery of social and medical
      care was necessary to meet individual child and family needs.

PMID- 16301939
TI  - Expert Patient Programme: managing patients with long-term conditions.
AB  - It is estimated that currently there may be as many as 17.5 million adults in
      Great Britain who are living with a long-term condition. Often these conditions
      will have a huge impact on the quality of life experienced by the person and any
      carers who might be involved. The impact on health care services is also
      profound. Long-term conditions potentially pose serious problems for healthcare
      systems in terms of adequate and appropriate resources to deal with the
      complexity of care required. Empowerment programmes which develop individuals'
      ability to self-manage their conditions are one way of helping people to maintain
      their independence and maximise their well-being. This article outlines one model
      (the Expert Patient Programme) and describes key issues with developing this
      approach in one acute Trust.

PMID- 16301940
TI  - Pilot study to show the loss of important data in nursing handover.
AB  - A good nursing handover process is a crucial part of providing quality nursing
      care in a modern healthcare environment. The conservation of patient data during
      the handover process is vital to ensure good continuity of care and safe
      practice. Any errors or omissions made during the handover process may have
      dangerous consequences. The authors observed the handover of 12 simulated
      patients over five consecutive handover cycles between nurses. Three handover
      styles were used and the amount of data loss was recorded for each style. A
      purely verbal handover style resulted in the loss of all data after three cycles.
      A note-taking style (the traditional style used in most hospital wards) resulted
      in only 31% of data being transferred correctly after five cycles. When a typed
      sheet was included with the verbal handover, data loss was minimal. Current
      handover methods may result in significant loss of important data that may impact
      on patient care. The authors recommend that prior to handover, a formal handover
      sheet be constructed that can be transferred as part of the handover process.

PMID- 16301941
TI  - The 'Been There, Done That' attitude.

PMID- 16301942
TI  - Hey, if they're good enough to kick Beckham out....

PMID- 16301943
TI  - Lean but not mean: economics of the NHS.

PMID- 16301944
TI  - Physiological and general health effects of chlamydia on men.
AB  - While chlamydia is a sexually transmitted infection that predominately affects
      females, this article concerns men and chlamydia. This article discusses the
      epidemiology, aetiology and signs and symptoms associated with a chlamydia
      infection. An outline of the consequences following infection will be presented
      along with the recommended treatment regimen. Chlamydia has the potential to
      become the interface between men's health and women's health. Most cases of
      chlamydia in women are a result of sexual contact with an infected man, and
      nearly all cases of chlamydia in the male, therefore, are the result of sexual
      contact with an infected woman. Addressing the sexual healthcare needs of men in
      relation to chlamydia has the potential to prevent the detrimental effects
      chlamydia may have on the female.

PMID- 16301945
TI  - Restoring pelvic floor function in men: review of RCTs.
AB  - The male pelvic floor muscles support the abdominal contents, are active during
      breathing, maintain urinary and faecal continence, increase local blood supply
      and are active during sexual intercourse. It was hypothesized that weak pelvic
      floor muscles would compromise these functions in men and lead to urinary and
      faecal incontinence and sexual dysfunction and that pelvic floor muscle
      strengthening would restore normal function. After a literature search of
      randomized controlled trials was undertaken, it was found that weak pelvic floor
      muscles compromised normal pelvic floor function and led to urinary incontinence
      and erectile dysfunction. Strengthening the pelvic floor muscles was shown to
      significantly improve post-prostatectomy urinary continence, post-micturition
      dribble and erectile function. It would be prudent for all men to exercise their
      pelvic floor muscles to maintain normal pelvic floor function.

PMID- 16301947
TI  - Consent to treatment records.
AB  - This article analyses the use of documentation to establish that consent has been
      given to treatment and that the necessary information about the possibility of
      significant risks of substantial harm has been given. The Department of Health
      has provided guidance as to when consent should be obtained in writing and also
      provided specimen forms which could be adapted for use by adults and young
      persons over 16 years; parents on behalf of children; procedures where no loss of
      consciousness is involved and for those situations where adults lack the capacity
      to give consent. The amendment of the forms is also considered together with
      discussion over the retention of the records.

PMID- 16301946
TI  - Use of lubricant in female urethral catheterization.
AB  - Urethral catheterization is a commonly undertaken nursing procedure, with up to
      12.6% of hospitalized and 4% of community patients having indwelling urethral
      catheters (Rew and Woodward, 2001). It is well known that this is often a
      procedure that can cause physical trauma to the urethra and can be painful for
      the patient and a recent systematic review identified that urethral trauma and
      discomfort could be minimized by using a sterile-use lubricant or anaesthetic gel
      (Department of Health, 2001). This article will consider the use of lubricants
      for female urethral catheterization.

PMID- 16301948
TI  - Angels and swingers, matrons and sinners: nursing stereotypes.
AB  - Media sexual stereotyping of the nursing profession is a well-recognized
      phenomenon; however the sexual stereotyping of the image of the nurse by the
      sex/pornography industry is a much less publicized or discussed phenomenon within
      the nursing profession. This paper aims to examine the presentation of the sexual
      stereotyping of nurses by newspapers and the sex/pornography industry. Both
      national and local newspapers in the UK frequently use derogatory terminology to
      depict the sexual stereotyping of nurses. Images and sexual stereotyping of
      nursing by the sex industry is also noted. The media was found to emphasize both
      positive and negative nursing stereotypes and in comparison with other
      occupations and professions sexual stereotyping was prevalent. The utilization of
      nursing imagery is also significantly visible across a wide range of pornographic
      and sex industry material.

PMID- 16301949
TI  - Case of the deputy ward manager who broke patient confidentiality.

PMID- 16301950
TI  - Identifying eating disorders.
AB  - While most nurses are familiar with anorexia and bulimia, how many nurses have
      heard of compulsive overeating, also known as binge eating? This is not a new
      condition but the medical profession has been very slow to recognize it as a
      problem, let alone as an eating disorder. This article looks at the different
      types of eating disorders, their differences, how to identify sufferers and where
      to refer them. Identifying patients with eating disorders is a very hard task
      since sufferers have learned the art of secrecy, denial and deception.

PMID- 16301951
TI  - The essence of continuing education in nursing.

PMID- 16301952
TI  - How does the media portray cancer?

PMID- 16301953
TI  - The experience of suffering as lived by women with breast cancer.
AB  - BACKGROUND: The advances in screening and treatment technologies for breast
      cancer allow many women to survive. However, their experience of suffering
      throughout this illness journey is not understood totally. AIM: To explore the
      experience of suffering as lived by women with breast cancer. DESIGN: A
      qualitative inquiry based on Heidegger's phenomenological approach was used to
      collect, code and analyse the data. Open-ended questions were asked to six women
      during an individual interview to allow the participants to voice their lived
      experiences. RESULTS: The voicing of their stories revealed a process of
      transformation as a response to the suffering experienced. The descriptions were
      deeply spiritual and connected to nature. The self-descriptions of their lived
      experience led to the construction of the Five Seasons of the Tree of Life.
      CONCLUSION: Nurses need to be cognizant of the multidimensionality of suffering
      so that interventions can be developed.

PMID- 16301954
TI  - Reviewing the progress of cancer networks in the UK.

PMID- 16301955
TI  - Loss of appetite: a poetic exploration of cancer patients' and their carers'
      experiences.
AB  - AIM: To explore the experience of loss of appetite among palliative care cancer
      patients and their carers supported by a specialist palliative care team in the
      community. METHOD: Semistructured interviews were conducted with seven palliative
      care cancer patients and their carers in the community. A poetic transcription of
      participants' words was made to capture and communicate the essence of each
      person's experience before the thematic analysis was undertaken. FINDINGS: Six
      common themes emerged from the data: a fickle phenomenon; the cost of caring;
      facing uncertainty and death; adaptations; accepting limitations; and what
      patients want: 'listen to me'. These were illustrated by the poetic
      transcriptions. CONCLUSION: Meeting the differing needs of palliative care
      patients with loss of appetite and their carers is challenging. It demands a
      thorough assessment of symptoms, an understanding of the underlying
      pathophysiology and of the role food plays in society. An understanding of the
      experience of loss of appetite is essential to the provision of appropriate care
      and support to those affected by it. The study demonstrated that, although
      unusual, poetic transcriptions can be an effective method of presenting data in
      terms of acceptability to participants and communicating their experience to
      others.

PMID- 16301956
TI  - Bereavement care for families part 1: a review of a paediatric follow-up
      programme.
AB  - The World Health Organization suggests that palliative care needs to offer a
      support system to the family during the patient's illness as well as during
      his/her bereavement. Bereavement follow-up services in paediatrics offer families
      an additional source of support in their grieving process. This article reviews
      the development of a bereavement follow-up programme delivered by the paediatric
      palliative care team and explores the lessons learnt and challenges faced in
      developing the programme.

PMID- 16301957
TI  - Palliative care for all: the global challenge.

PMID- 16301958
TI  - What influences decisions around the place of care for terminally ill cancer
      patients?
AB  - AIM: To explore what factors influence decisions around the place of care for
      terminally ill cancer patients in a rural area in West Highland, Scotland.
      DESIGN: This was a descriptive, explorative, qualitative study using taped
      semistructured interviews. SAMPLE: A purposive sample of eight terminally ill
      cancer patients. RESULTS: The determinants for the desired place of care were
      organized into three main themes: carer resource and support; past experiences
      with death; and communication of wishes. The study evidenced that individuals
      often changed their preferred place of care at the end of life as the need for
      care increased. Those involved in the study found a therapeutic and emotional
      benefit by being able to discuss end-of-life care in a safe and secure
      environment. CONCLUSION: For many, the preference for place of care at the end of
      life was conditional on how the process of their disease advanced. It was not a
      clear and positive choice, but it did include the desire to be cared for in a
      place other than home. Carer availability and ability were influencing factors;
      however, decisions reflected the patient's perceptions of resources rather than
      those of the carer, even when the carer was available and able. The challenge to
      those who work with the terminally ill is to develop effective interventions to
      facilitate discourses around end-of-life care, and thereafter, where possible, to
      facilitate those preferences.

PMID- 16301959
TI  - [Bird flu: too much ado about it?].

PMID- 16301960
TI  - [Defending clinical research in anorexia nervosa].

PMID- 16301961
TI  - [Retrospective study of anorexia nervosa: reduced mortality and stable recovery
      rates].
AB  - OBJECTIVES: Anorexia nervosa is an eating disorder that combines malnutrition,
      amenorrhea, and distorted body image. To learn more about the course of this
      disease we undertook a retrospective study of girls diagnosed with anorexia
      nervosa in the Saint Etienne Endocrinology Department between 1979 and 2004.
      METHODS: Patients were diagnosed according to DSMIV criteria. Data collected to
      complete the Morgan-Russell outcome assessment schedule included chronology of
      illness, patients' morphological features, anorexia type, treatment choice,
      patient's gynecological history, and social status. RESULTS: The study included
      206 cases. The average follow-up period was 8.3 +/- 5.3 years. Defining recovery
      as stable BMI>17.5 kg/m2 for at least one year and recovery of normal
      menstruation, full recovery was observed in 55.8% and partial recovery in 25.7%,
      while 18.5% remained chronically ill. Early onset (i.e., during adolescence) was
      associated with good prognosis, and advanced emaciation and delayed or
      insufficient medical care with poor prognosis. CONCLUSIONS: The seriousness of
      this disease is due more to the incidence of cases that become chronic than to
      the mortality rate. Prediction of severity would be improved by taking into
      account underlying personality traits, such as addictive tendencies and
      depression.

PMID- 16301962
TI  - [Immune reconstitution syndrome and mycobacterial disease during highly active
      antiretroviral therapy. Retrospective study of six cases].
AB  - INTRODUCTION: Soon after starting highly active antiretroviral therapy (HAART),
      some patients experience clinical deterioration due to the reactivation of their
      immune system. Mycobacteria are the principal agents complicating this immune
      reconstitution period. CASES: A retrospective examination of patients with
      mycobacterial disease before or shortly after beginning HAART at Grenoble
      University Hospital from January 2001 through July 2004 identified six subjects
      (among 650 outpatients per year) with a new or aggravated mycobacterial disease
      after starting HAART. Clinical manifestations were: adenopathy (4/6),
      hyperthermia (3/6), thoracic pain (2/6), abscess (2/6), and neurological
      deterioration (1/6). DISCUSSION: Severely immunosuppressed patients who begin
      HAART may reactivate or aggravate a mycobacterial disease such as tuberculosis.
      In such cases, current recommendations call for continuing HAART, beginning or
      continuing the antimycobacterial therapy, and considering corticosteroids on a
      case-by-case basis. For patients with AIDS, opportunistic infections that might
      be reactivated should be actively sought before HAART.

PMID- 16301963
TI  - [Intimal sarcoma of the inferior vena cava].
AB  - INTRODUCTION: Primary sarcomas of the great vessels, that is, the aorta,
      pulmonary artery, and inferior vena cava, are rare. They can be classified
      according to the location of the sarcoma in the vessel wall and by their gross
      appearance. Most often they are leiomyosarcomas or fibrosarcomas. CASE: We report
      here a case of an intimal sarcoma of the inferior vena cava. Histological and
      immunohistochemical findings confirmed the diagnosis for this 17-year-old girl
      and distinguished it from leiomyosarcoma and angiosarcoma, both of which have
      better prognoses. DISCUSSION: Intimal sarcoma of the inferior vena cava is rare
      and difficult to diagnose before surgery or biopsy. Histologically, it is a
      poorly differentiated tumor with the worst prognosis among the primary vascular
      sarcomas. Pathologic findings and immunohistochemical staining are useful for a
      positive diagnosis.

PMID- 16301964
TI  - [Osteofluorosis caused by excess use of toothpaste].
AB  - BACKGROUND: Osteofluorosis is caused by chronic fluoride intoxication. Fluoride
      is used in toothpaste for the prevention of dental caries, and dental fluorosis
      has often been reported among children and attributed to ingestion of fluoride
      toothpaste. We report a case of chronic fluoride intoxication caused by excess
      use of toothpaste in an adult. CASE: A 45-year-old woman consulted a
      rheumatologist for painful swelling of the fingers, phalangeal rather than
      articular. She also had brown staining on her teeth. Radiography of the hands
      showed periosteal apposition on the phalanges. Further work-up ruled out tumoral
      or thyroid causes. Laboratory tests showed elevated fluoride levels in the blood
      (50.9 micromol/L, normal<1.5 micromol/L) and in the urine (721 micromol/L,
      normal<46 micromol/L). On questioning, we found only one cause for chronic
      fluoride intoxication: excess and unusual use of toothpaste. The patient brushed
      her teeth 18 times a day and swallowed the toothpaste, because she liked the
      taste. She consumed a tube of toothpaste every 2 days, thereby swallowing 68.5 mg
      of fluoride every day. Suspecting fluorosis from toothpaste, we asked the patient
      to use a toothpaste without fluoride. Sixteen weeks later, the pain had ceased,
      and laboratory tests showed massively reduced but still elevated fluoride levels
      in the blood (6.9 micromol/L) and urine (92.7 micromol/L). CONCLUSION: In this
      rare case of fluoride intoxication, misuse of a normally innocuous product caused
      osteofluorosis.

PMID- 16301965
TI  - [Whipple disease, initially diagnosed as sarcoidosis].
AB  - INTRODUCTION: Whipple disease is a multisystem infectious disease caused by
      Tropheryma whipplei. We report a case in which an initial diagnosis of
      sarcoidosis was changed to Whipple disease endocarditis. CASE: Based on clinical,
      radiographic, endoscopic and histologic findings, this 61-year-old man was
      diagnosed with sarcoidosis. Initial response to corticotherapy was good, but the
      patient required 35 mg of prednisone daily. The subsequent onset of clinical and
      laboratory signs of inflammation cast doubt on the diagnosis. After cardiac
      ultrasound revealed a mass 1 cm in diameter on the mitral valve, apparently
      vegetation, we diagnosed culture-negative infective endocarditis and ruled out
      most possible causes. PCR of a duodenal biopsy sample showed Tropheryma whipplei,
      thus confirming the diagnosis of Whipple disease, despite normal histological
      findings. After 3 weeks of intravenous gentamicin and amoxicillin treatment, oral
      cotrimoxazole was substituted. Follow-up transesophageal ultrasound showed no
      mitral vegetation. The patient, still under cotrimoxazole, has been off
      prednisone for 13 months and is completely asymptomatic. CONCLUSION: This case is
      an illustration of the difficulty in distinguishing Whipple disease from
      sarcoidosis in practice and of the importance of that distinction.

PMID- 16301966
TI  - [Significance of cholesterol levels in patients 75 years or older].
AB  - Increasing comorbidity with aging reduces the predictive power of cardiovascular
      risk factors. From the age of 70 onward, total cholesterol levels decrease,
      perhaps associated with changes in the composition of some lipoprotein fractions.
      In subjects older than 75 years, being in the lowest quartile of cholesterol,
      insulinemia or serum albumin concentrations is associated with increased
      mortality. Cholesterol levels below 189 mg/dL in subjects older than 75 years
      should be considered an early sign of unidentified comorbidity or of rapid
      functional decline. HDL cholesterol levels, rather than total or LDL cholesterol,
      were inversely associated with increased mortality from ischemic coronary disease
      and stroke appears to rise as HDL cholesterol levels fall, rather than total or
      LDL cholesterol. On the other hand, LDL concentrations below 106 mg/dL and HDL
      concentrations below 36 mg/dL were associated with an increased risk of death
      from infectious disease. Stroke incidence, in particular, ischemic stroke, is
      highest in subjects older than 75 years. HDL cholesterol levels above 35 mg/dL
      appear to have a protective effect against ischemic stroke in subjects younger
      than 70 years. Two interventional drug studies investigating the effects of two
      statins (simvastatin and pravastatin) found that in subgroups of subjects older
      than 75 these drugs were associated with a reduction in all-cause mortality and
      cardiovascular morbidity, regardless of total cholesterol levels, but had no
      short-term effect on cognitive function.

PMID- 16301967
TI  - [Obstructive sleep apnea syndrome].
AB  - Obstructive sleep apnea syndrome is characterized by recurrent total or partial
      upper airway collapse during sleep. Although this disease affects more than 5% of
      general population, it remains largely undiagnosed. It is associated with an
      increase in cardiovascular risk and with a decrease in sustained attention that
      may cause automobile accidents or occupational injuries. Several simplified
      diagnostic tools (polysomnography) now allow easier diagnosis in a sleep
      laboratory or on an outpatient basis. Nasal continuous positive airway pressure
      remains the reference treatment, acting as a pneumatic splint that maintains
      airway patency. CPAP is effective in reducing daytime somnolence and controlling
      cardiovascular risk. Prosthetic management is an alternative to CPAP in cases of
      moderate sleep apnea with or without retrognathism in normal-weight patients. The
      effectiveness of surgery has not been proven, and it is indicated only in
      exceptional cases.

PMID- 16301968
TI  - [Do serial ANCA titres predict relapse in ANCA-associated vasculitis?].
AB  - Antineutrophil cytoplasm autoantibodies (ANCA) are essential for the diagnosis of
      small-vessel vasculitis. Information for and against their usefulness to predict
      relapse exists. Different approaches, using various methods and definitions, have
      been used to answer the role of ANCA in predicting disease relapse.
      Multinational, multicentric prospective studies are needed to address this
      question using uniform definitions and preferably the best latest tools for ANCA
      detection.

PMID- 16301969
TI  - [Consensus statement on severe dementia].
AB  - Under the auspices of the French Society of Gerontology and Geriatrics, a
      multidisciplinary group of experts, including geriatricians, neurologists,
      epidemiologists, psychiatrists, pharmacologists, and public health specialists
      developed consensus recommendations about care for patients with severe dementia.
      They defined 21 recommendations for general practitioners, long-term care
      physicians, and specialists, based on the knowledge currently available (2005).
      The aim of care at all stages is to mitigate the quality-of-life of patient,
      caregiver, and family insofar as possible, combining care and future planning
      until the end of life. Management, to take into account problems including
      nutritional status, behavior disorders, and ability (or inability) to perform
      activities of daily living, must be global, multidisciplinary, and coordinated
      and must optimize use of local medical and social resources. The group also
      stressed the importance of clinical research to improve knowledge of disease
      course and assess management strategies and recommended specific area for
      research.

PMID- 16301970
TI  - [Magnetic resonance images of amyotrophic lateral sclerosis].

PMID- 16301971
TI  - [Better breast cancer screening: how?].

PMID- 16301972
TI  - [Perspectives on pulmonary vascular diseases].

PMID- 16301973
TI  - [Diagnostic approach to venous thromboembolic disease].
AB  - The diagnosis of pulmonary embolism (PE) and deep venous thrombosis (DVT) has
      long been based on purely clinical grounds. Pulmonary angiography and
      scintigraphy, as well as venography, reveal the poor diagnostic value of signs
      and symptoms of PE and DVT, which are now reduced to the role of triggers for
      these diagnostic tests. The development of simpler, but still imperfect,
      diagnostic tools (mainly, D-dimer plasma level, venous compression ultrasound,
      clinical probability of PE or DVT, spiral CT pulmonary angiography) has led to
      the development of diagnostic strategies, which use combinations of tests, not to
      provide diagnostic certainty for every patient (presence or absence of clots),
      but rather to select populations of patients who need treatment and others who
      can safely remain untreated. Such pragmatic approaches must be validated in
      appropriate outcome studies. The choice of a diagnostic strategy should depend
      not only on the strategy's cost-effectiveness in the population under study but
      also on the local facilities and expertise required for its use.

PMID- 16301974
TI  - [Treatment of venous thromboembolic disease].
AB  - Adequate initial anticoagulant treatment is required to prevent thrombus growth
      and recurrence. Intravenous unfractionated heparin is being replaced by low
      molecular-weight heparin as the anticoagulant of choice for initial treatment of
      venous thromboembolism. Vitamin K antagonists remain the only oral anticoagulant
      available (target international normalized ratio: 2.5). The duration of therapy
      should be individualized according to the risk of recurrence and the risk of
      bleeding. Three months of treatment is usually adequate if thrombosis was
      provoked by a reversible risk factor such as surgery. For patients with
      unprovoked ("idiopathic") thrombosis, anticoagulant treatment for at least 6
      months is indicated. For patients with a recurrence of venous thromboembolism or
      with an irreversible risk factor such as cancer, indefinite anticoagulant therapy
      is recommended. Long-term treatment with low-molecular-weight heparin is usually
      preferable for patients with active cancer. Systemic thrombolysis is indicated
      for patients with massive pulmonary embolism but controversy persists for those
      with isolated right ventricular dysfunction.

PMID- 16301975
TI  - [Diagnosis and classification of pulmonary arterial hypertension].
AB  - The clinical classification of types of pulmonary hypertension has made it
      possible to better standardize the approach to the diagnosis and treatment of
      patients, to perform clinical studies among homogeneous patients, and to discover
      common laboratory abnormalities that may serve as markers or help elucidate
      mechanisms of disease. Pulmonary arterial hypertension groups together different
      diseases that affect the small-caliber pulmonary arteries and lead to a
      progressive increase in pulmonary arterial resistance and right heart failure. A
      specific diagnosis of pulmonary arterial hypertension is generally based on a
      detailed and methodical clinical evaluation. Pulmonary biopsy is rarely
      indicated. Work-up in a center specialized in the management of this disease is
      frequently appropriate when the cause of the hypertension is not clear or when a
      specific treatment is envisaged.

PMID- 16301976
TI  - [Treatment of pulmonary arterial hypertension].
AB  - Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, in
      situ thrombosis, and vascular remodeling of small pulmonary arteries. It induces
      a fixed pulmonary arterial obstruction, persistent elevation of pulmonary
      arterial resistance, and eventually right heart failure. Conventional therapy is
      based on simple measures (exercise limitation) and nonspecific treatments
      (warfarin, diuretics, and oxygen). Pure vasodilators, such as calcium channel
      blockers, are effective only in a minority of patients who have an acute response
      to vasodilator testing. Intravenous prostacyclin (epoprostenol) and endothelin
      receptor blockers have vasodilator and antiproliferative properties. Epoprostenol
      therapy has significantly improved PAH prognosis and remains the first-line
      treatment for patients with the most severe disease. Bosentan is an interesting
      first-line treatment for NYHA functional class III patients. Availability of
      novel specific drugs (endothelin receptor type A antagonists, prostacyclin
      analogues, type 5 phosphodiesterase inhibitors) is opening new perspectives in
      PAH treatment. The long-term benefit of these drugs remains to be evaluated and
      their respective place in treatment of these patients is still uncertain. The
      evolution of therapy from vasodilators to antiproliferative agents reflects the
      advancement in our understanding of the mechanisms mediating pulmonary arterial
      hypertension.

PMID- 16301977
TI  - [Treatment for pulmonary arterial hypertension under the new French hospital
      financing system. Recommendations of the Pulmonary Vascular Diseases Working
      Group of the French Society of Pulmonary Medicine].
AB  - Activity-based financing (that is, casemix-based hospital payments, known as T2A)
      is intended to harmonize and improve the fairness of remuneration of public and
      private hospitals. T2A will ultimately rely mainly on a flat rate per admission,
      set according to the diagnosis-related group (DRG). Although payment for drugs is
      usually included in the DRG price, some expensive drugs will be reimbursed on an
      additional cost basis after implementation of a "best practices" agreement. Four
      drugs used for treatment of pulmonary arterial hypertension are eligible for this
      additional reimbursement: 3 prostacyclin derivatives (intravenous epoprostenol,
      inhaled iloprost, and subcutaneous treprostinil), and oral bosentan, an
      endothelin receptor antagonist. The Pulmonary Vascular Diseases working group of
      the French Society of Pulmonary Medicine has developed guidelines for the best
      practices in use of these drugs.

PMID- 16301978
TI  - [Pulmonary hypertension associated with disorders of the respiratory system].
AB  - Pulmonary hypertension associated with disorders of the respiratory system is
      defined by a pulmonary artery mean pressure above 20 mmHg at rest in stable
      disease. The most frequent form of precapillary pulmonary hypertension is
      associated with chronic obstructive pulmonary disease, because of its high
      prevalence. Pulmonary vascular remodeling occurs in the small pulmonary arteries
      and is due mainly to chronic alveolar hypoxia. Pulmonary hypertension associated
      with disorders of the respiratory system is usually mild to moderate, with
      resting pulmonary artery mean pressure ranging between 20 and 35 mm Hg. It may
      increase markedly during sleep, exercise or exacerbation of respiratory failure,
      however. Abrupt postload elevation can lead to right heart failure, an
      indisputable indicator of prognosis. Because the symptoms of pulmonary
      hypertension are minimal relative to those of the chronic hypoxic lung disease,
      noninvasive diagnosis is difficult, particularly in patients with chronic
      obstructive pulmonary disease. Oxygen therapy (at least 16 h/day) is currently
      the best treatment for this type of pulmonary arterial hypertension.

PMID- 16301979
TI  - [Surgical treatment of chronic thromboembolic pulmonary hypertension].
AB  - Chronic thromboembolic pulmonary hypertension is a condition that has long
      remained in the shadows, a kind of orphan disease, because of the lack of any
      curative treatment. The renewal of interest by pulmonary specialists,
      cardiologists and thoracic surgeon is due to the development over the past 20
      years of major new treatments: lung transplantation, continuous prostacyclin
      infusion, and pulmonary endarterectomy, in chronological order. Most patients
      with postembolic pulmonary arterial hypertension (PEPAH) in a sufficiently
      proximal location can benefit from curative surgical treatment by bilateral
      endarterectomy of the pulmonary arteries. This complex surgery, performed under
      deep hypothermic circulatory arrest, clears out the pulmonary vascular bed down
      through its subsegmental branches and results in a frank reduction in pulmonary
      vascular resistance and normalization of cardiopulmonary function. It is a
      curative procedure with a perioperative mortality rate less than 7% and a
      definitive result, unlike pulmonary and cardiopulmonary transplantation, which
      have a postoperative mortality rate of 20% and a 5-year survival rate of 50%. It
      is difficult to recognize the postembolic nature of pulmonary hypertension
      because there is no known history of venous thrombosis or embolic phenomena in
      more than 50% of cases. Diagnosis is based on the presence of mismatched
      segmental defects in the radioisotopic ventilation-perfusion scanning. To be
      accessible to endarterectomy, lesions must involve the main, lobar, or segmental
      arteries. When conducted by experienced operators according to specific
      protocols, pulmonary (frontal and lateral views of each lung) and multislice CT
      angiography optimize assessment of the lesion site. When the pulmonary vascular
      resistance evaluated by catheterization is correlated with the anatomical
      obstruction visible on the images, pulmonary endarterectomy has a mortality rate
      below 4% and offers the patient a substantial chance to regain normal
      cardiorespiratory function. In cases of pulmonary arterial hypertension due to
      older embolisms, major arteriolitis occurs in the nonobstructed areas and
      aggravates the pulmonary hypertension, which may become suprasystemic. The
      endarterectomy mortality rate is then higher, and in specific cases justifies
      preoperative medical treatment. Pulmonary or cardiopulmonary transplantation is
      indicated in this disease only when the lesions are too distal and thus
      inaccessible to endarterectomy.

PMID- 16301980
TI  - [Pulmonary vascular manifestations in hereditary hemorrhagic telangiectasia].
AB  - Hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber disease) is a genetic
      disorder with autosomal dominance, variable penetrance, and an estimated
      prevalence of 1/10,000 inhabitants in France. Diagnosis is based on clinical
      criteria including epistaxis, telangiectasia, visceral manifestations, and
      familial occurrence. Pulmonary arteriovenous malformations, present in 15-33% of
      patients, are its primary visceral complications. The disease may be revealed by
      infectious and ischemic neurological manifestations due to paradoxical embolism.
      The high frequency of neurologic complications even in asymptomatic patients
      justifies systematic screening for pulmonary arteriovenous malformations.
      Treatment of these malformations is based on percutaneous transcatheter coil
      embolization of the feeding artery. Pulmonary arterial hypertension is rare in
      this disease. It may be due to systemic arteriovenous shunting in the liver,
      which increases cardiac output, or be similar to idiopathic pulmonary
      hypertension.

PMID- 16301981
TI  - Health highlights. Good news that greeted women in 2005.

PMID- 16301982
TI  - Risk of tooth loss greater in postmenopausal women.

PMID- 16301983
TI  - Eating fruits and vegetables may reduce cataract risk in women.

PMID- 16301985
TI  - Wound repair. The remarkable healing power of the human body.

PMID- 16301984
TI  - Keeping ovaries may aid long-term health, survival.

PMID- 16301986
TI  - DHEA supplements. Benefits are promising, but proof is lacking.

PMID- 16301987
TI  - Mayo Clinic office visit. Independent living. An interview with Paul Takahashi,
      M.D.

PMID- 16301988
TI  - Get a move on. Exercising when walking is not an option.

PMID- 16301989
TI  - How long can the average woman expect to live these days?

PMID- 16301990
TI  - Should I follow a special diet while taking warfarin?

PMID- 16301991
TI  - Will taking an antidepressant cause me to gain weight?

PMID- 16301992
TI  - v-Src requires Ras signaling for the suppression of gap junctional intercellular
      communication.
AB  - Cell transformation by v-Src causes suppression of gap junctional intercellular
      communication (GJIC). Although tyrosine phosphorylation of connexin43 (Cx43), a
      gap junctional component, appears to be necessary for the suppression,
      involvement of other signaling remains unclear. We investigated the role of Ras
      signaling in the suppression of GJIC by v-Src. Conditional expression of either
      S17N Ras or mtGap1m dramatically recovered GJIC in v-Src-transformed cells.
      Although expression of S17N Ras or mtGap1m substantially decreased the levels of
      active Ras, tyrosine phosphorylation of cellular proteins including Cx43 remained
      unchanged. Similarly, treatment of v-Src-transfomed cells with a Ras
      farnesyltransferase inhibitor, manumycin A, restored GJIC, whereas tyrosine
      phosphorylation of Cx43 remained unchanged. Thus, these results strongly suggest
      that, in addition to Cx43 phosphorylation, constitutive activation of Ras
      signaling is required for the suppression of GJIC by v-Src.

PMID- 16301993
TI  - The G12/13-RhoA signaling pathway contributes to efficient lysophosphatidic acid
      stimulated cell migration.
AB  - The membrane redistribution and phosphorylation of focal adhesion kinase (FAK)
      have been reported to be important for cell migration. We previously showed that
      Lysophosphatidic acid (LPA) induced FAK membrane redistribution and
      autophosphorylation in ovarian cancer SK-OV3 cells and the signaling pathway
      consisting of Gi-Ras-MEKK1 mediated LPA-induced FAK membrane redistribution but
      not FAK autophosphorylation. We also showed that the disruption of the Gi-Ras
      MEKK1 pathway led to a significant reduction in LPA-stimulated cell migration.
      These findings raised the question of whether LPA-induced FAK autophosphorylation
      was required for LPA-stimulated cell migration and what signaling mechanism was
      involved in LPA-induced FAK autophosphorylation. In this study, we expressed the
      membrane anchored wild-type FAK (CD2-FAK) in SK-OV3 cells and found that the
      expression of CD2-FAK greatly rescued LPA-stimulated cell migration in Gi or Ras
      inhibited cells. However, Gi inhibitor pertussis toxin or dominant-negative H-Ras
      still significantly inhibited LPA-stimulated cell migration in cells expressing
      the membrane anchored FAK containing a mutation in the autophosphorylation site
      [CD2-FAK(Y397A)]. These results suggest that FAK autophosphorylation plays a role
      in LPA-stimulated cell migration. With the aid of p115RhoGEF-RGS, G12 and G13
      minigenes to inhibit G12/13, we found that the G12/13 pathway was required for
      LPA-induced FAK autophosphorylation and efficient cell migration. Moreover, LPA
      activated RhoA and Rho kinase (ROCK) in a G12/13-dependent manner and their
      activities were required for LPA-induced FAK autophosphorylation. However, Rho or
      ROCK inhibitors displayed no effect on LPA-induced FAK membrane redistribution
      although they abolished LPA-induced cytoskeleton reorganization. Our studies show
      that the G12/13-RhoA-ROCK signaling pathway mediates LPA-induced FAK
      autophosphorylation and contributes to LPA-stimulated cell migration.

PMID- 16301994
TI  - Regulation of cyclin D2 and the cyclin D2 promoter by protein kinase A and CREB
      in lymphocytes.
AB  - Lymphocyte proliferation is key to the regulation of the immune system. Cyclin D2
      is the first cell cycle protein induced following stimulation through the T-cell
      receptor, the B-cell receptor or cytokines. The promoter of this cyclin
      integrates a diverse range of signals. Through investigating the regulation of
      this promoter by interleukin-2 and phosphatidylinositol 3-kinase, we have
      identified a role for the transcription factor CREB, cAMP response element
      binding protein. Mutation of the CREB-binding site reduced cyclin D2 promoter
      activity 5-10-fold. CREB-1 is phosphorylated at serine 133, a critical site for
      activity, in both T cells and Epstein-Barr virus immortalized B cells. The
      introduction of an S133A mutant of CREB-1 reduces IL-2 induction of cyclin D2
      promoter activity, demonstrating a role for this phosphorylation site in promoter
      activity. Two inhibitors of protein kinase A reduce lymphocyte proliferation and
      CREB-1 phosphorylation. This study demonstrates that the cyclin D2 promoter is
      capable of being regulated by PI3K and CREB and identifies CREB-1 and protein
      kinase A as potential targets for altering lymphocyte proliferation.

PMID- 16301995
TI  - Identification of the p53 family-responsive element in the promoter region of the
      tumor suppressor gene hypermethylated in cancer 1.
AB  - The tumor suppressor gene hypermethylated in cancer 1 (HIC1), located on human
      chromosome 17p13.3, is frequently silenced in cancer by epigenetic mechanisms.
      Hypermethylated in cancer 1 belongs to the bric a brac/poxviruses and zinc-finger
      family of transcription factors and acts by repressing target gene expression. It
      has been shown that enforced p53 expression leads to increased HIC1 mRNA, and
      recent data suggest that p53 and Hic1 cooperate in tumorigenesis. In order to
      elucidate the regulation of HIC1 expression, we have analysed the HIC1 promoter
      region for p53-dependent induction of gene expression. Using progressively
      truncated luciferase reporter gene constructs, we have identified a p53
      responsive element (PRE) 500 bp upstream of the TATA-box containing promoter P0
      of HIC1, which is sequence specifically bound by p53 in vitro as assessed by
      electrophoretic mobility shift assays. We demonstrate that this HIC1 p53
      responsive element (HIC1.PRE) is necessary and sufficient to mediate induction of
      transcription by p53. This result is supported by the observation that abolishing
      endogenous wild-type p53 function prevents HIC1 mRNA induction in response to UV
      induced DNA damage. Other members of the p53 family, notably TAp73beta and
      DeltaNp63alpha, can also act through this HIC1.PRE to induce transcription of
      HIC1, and finally, hypermethylation of the HIC1 promoter attenuates inducibility
      by p53.

PMID- 16301996
TI  - DDX3, a DEAD box RNA helicase, is deregulated in hepatitis virus-associated
      hepatocellular carcinoma and is involved in cell growth control.
AB  - Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths
      worldwide and is highly correlated with hepatitis virus infection. Our previous
      report shows that a DEAD box RNA helicase, DDX3, is targeted and regulated by
      hepatitis C virus (HCV) core protein, which implicates the involvement of DDX3 in
      HCV-related HCC development. In this study, the potential role of DDX3 in
      hepatocarcinogenesis is investigated by examining its expression in surgically
      excised human HCC specimens. Here we report the differential deregulation of DDX3
      expression in hepatitis virus-associated HCC. A significant downregulation of
      DDX3 expression is found in HCCs from hepatitis B virus (HBV)-positive patients,
      but not from HCV-positive ones, compared to the corresponding nontumor tissues.
      The expression of DDX3 is differentially regulated by the gender and, moreover,
      there is a tendency that the downregulation of DDX3 expression in HCCs is more
      frequent in males than in females. Genetic knockdown of DDX3 with small
      interfering RNAs (siRNA) in a nontransformed mouse fibroblast cell line, NIH-3T3,
      results in a premature entry to S phase and an enhancement of cell growth. This
      enhanced cell cycle progression is linked to the upregulation of cyclin D1 and
      the downregulation of p21(WAF1) in the DDX3 knockdown cells. In addition,
      constitutive reduction of DDX3 expression increases the resistance of NIH-3T3
      cells to serum depletion-induced apoptosis and enhances the ras-induced anchorage
      independent growth, indicating the involvement of DDX3 in cell growth control.
      These findings together with the previous study suggest that the deregulation of
      DDX3, a DEAD box RNA helicase with cell growth-regulatory functions, is involved
      in HBV- and HCV-associated pathogenesis.

PMID- 16301997
TI  - Functional Fas (Cd95/Apo-1) promoter polymorphisms in inbred mouse strains
      exhibiting different susceptibility to gamma-radiation-induced thymic lymphoma.
AB  - The Fas death receptor is a cell surface molecule involved in apoptosis as well
      as in proliferative or activating signals of many cells types, including T
      lymphocytes. Using quantitative real-time reverse transcription-PCR analysis, we
      confirm that expression of this gene is scarcely perceptible in thymic lymphomas
      induced by gamma-irradiation in C57BL/6J mice. Notably, we also demonstrate for
      the first time that Fas expression is significantly upregulated in vivo both
      after single high dose of radiation and in thymic lymphoma-free mice. In
      addition, we determined its levels of expression in five mouse strains exhibiting
      different degrees of susceptibility (SPRET/Ei, SEG/Pas, BALB/cJ, C57BL/6J and
      RF/J). Interestingly, we found the highest levels of expression in SPRET/Ei and
      SEG/Pas strains (both derived from the Mus spretus species), which are known to
      have the most resistant phenotype, and the lowest levels in the most susceptible
      strains C57BL/6J and RF/J. DNA sequencing of the Fas promoter in all five strains
      showed many polymorphisms that can be classified into three functional haplotypes
      by using luciferase assays: (1) C57BL/6J and RF/J, (2) BALB/cJ and (3) SPRET/Ei
      and SEG/Pas. Promoter activities in response to single high doses of radiation
      correlated well with the levels of Fas expression and are consistent with the
      degree of strain susceptibility.

PMID- 16301998
TI  - Dissociation of caspase-mediated events and programmed cell death induced via HLA
      DR in follicular lymphoma.
AB  - Human leukocyte antigens (HLA) class II antigen-mediated apoptosis has been
      documented in antigen-presenting cells and B lymphoproliferations.
      Characteristics of the apoptosis include rapidity and selectivity for mature
      cells. Follicular lymphomas are particularly refractory to apoptosis. The B-cell
      lymphoma Ramos shares characteristics of this subgroup and is insensitive to
      apoptosis via simple HLA-DR engagement. However, oligomerization of HLA-DR
      antigens induced caspase activation followed by phosphatidylserine
      externalization, activation of PKC-delta and cleavage of nuclear lamin B.
      Mitochondrial injury was also detected. However, inhibition of caspase activation
      simply delayed the apoptotic phenotype but neither protected against cell death
      nor prevented mitochondrial injury. The data in this report demonstrate that the
      requirements for the initiating signal (oligomerization versus engagement) as
      well as the molecular pathways varies between different B lymphoproliferations
      despite their common expression of HLA-DR. Finally, blockade of caspase
      activation in parallel with HLA-DR mAb stimulation could provide a potent
      autovaccination stimulus by leading to necrotic death of B-cell lymphomas.

PMID- 16301999
TI  - Thioredoxin-interacting protein (txnip) is a glucocorticoid-regulated primary
      response gene involved in mediating glucocorticoid-induced apoptosis.
AB  - Glucocorticoid hormones induce apoptosis in lymphoid cells. This process is
      transcriptionally regulated and requires de novo RNA/protein synthesis. However,
      the full spectrum of glucocorticoid-regulated genes mediating this cell death
      process is unknown. Through gene expression profiling we discovered that the
      expression of thioredoxin-intereacting protein (txnip) mRNA is significantly
      induced by the glucocorticoid hormone dexamethasone not only in the murine T-cell
      lymphoma line WEHI7.2, but also in normal mouse thymocytes. This result was
      confirmed by Northern blot analysis in multiple models of dexamethasone-induced
      apoptosis. The induction of txnip mRNA by dexamethasone appears to be mediated
      through the glucocorticoid receptor as it is blocked in the presence of RU486, a
      glucocorticoid receptor antagonist. Deletion and mutation analysis of the txnip
      promoter identified a functional glucocorticoid response element in the txnip
      promoter. Reporter assays demonstrated that this glucocorticoid response element
      was necessary and sufficient for induction of txnip by dexamethasone. Expression
      of a GFP-TXNIP fusion protein was sufficient to induce apoptosis in WEHI7.2
      cells, and repression of endogenous txnip by RNA interference inhibited
      dexamethasone-induced apoptosis in WEHI7.2 cells. Together, these findings
      indicate that txnip is a novel glucocorticoid-induced primary target gene
      involved in mediating glucocorticoid-induced apoptosis.

PMID- 16302000
TI  - G-Quadruplex stabilization by telomestatin induces TRF2 protein dissociation from
      telomeres and anaphase bridge formation accompanied by loss of the 3' telomeric
      overhang in cancer cells.
AB  - Inhibition of telomerase activity by telomerase inhibitors induces a gradual loss
      of telomeres, and this in turn causes cancer cells to enter to a crisis stage.
      Here, we report the telomerase inhibitor telomestatin, which is known to
      stabilize G-quadruplex structures at 3' single-stranded telomeric overhangs (G
      tails), rapidly dissociates TRF2 from telomeres in cancer cells within a week,
      when given at a concentration that does not cause normal cells to die. The G
      tails were dramatically reduced upon short-term treatment with the drug in cancer
      cell lines, but not in normal fibroblasts and epithelial cells. In addition,
      telomestatin also induced anaphase bridge formation in cancer cell lines. These
      effects of telomestatin were similar to those of dominant negative TRF2, which
      also causes a prompt loss of the telomeric G-tails and induces an anaphase
      bridge. These results indicate that telomestatin exerts its anticancer effect not
      only through inhibiting telomere elongation, but also by rapidly disrupting the
      capping function at the very ends of telomeres. Unlike conventional telomerase
      inhibitors that require long-term treatments, the G-quadruplex stabilizer
      telomestatin induced prompt cell death, and it was selectively effective in
      cancer cells. This study also identifies the TRF2 protein as a therapeutic target
      for treating many types of cancer which have the TRF2 protein at caps of the
      telomere DNA of each chromosome.

PMID- 16302001
TI  - QN1/KIAA1009: a new essential protein for chromosome segregation and mitotic
      spindle assembly.
AB  - We previously reported the involvement of QN1 (quail neuroretina 1) protein in
      cell cycle control during retinal development. We show here that QN1 is an ATPase
      conserved through evolution, from fugu to humans. We show that chicken/quail QN1
      protein is orthologous to the KIAA1009 protein in humans, the function of which
      was not known. We demonstrate here for the first time that QN1/KIAA1009 protein
      is located at the spindle poles of the mitotic apparatus and at centrosomes
      during mitosis. The siRNA-mediated depletion of KIAA1009 led to abnormal mitosis
      with chromosome segregation defects and abnormal centrosome separation leading to
      the death of PC12 and MCF7 cells. Thus, QN1/KIAA1009 is a new microtubule
      associated ATPase involved in cell division.

PMID- 16302002
TI  - Neuroendocrine-like differentiation of non-small cell lung carcinoma cells:
      regulation by cAMP and the interaction of mac25/IGFBP-rP1 and 25.1.
AB  - The need to develop more effective therapies for lung cancer has led to
      investigations in understanding the molecular mechanisms of the differentiation
      process, in particular neuroendocrine (NE) differentiation. Recent studies have
      demonstrated that NE differentiation in non-small cell lung carcinoma (NSCLC) is
      not uncommon. Those NSCLCs with NE differentiation are considered a form of in
      transition NE carcinoma and show a more aggressive clinical course compared with
      NSCLC without NE differentiation. 25.1, a novel protein interacting with
      mac25/insulin-like growth factor-binding protein-related protein 1 (mac25/IGFBP
      rP1), induced NE-like differentiation when collectively overexpressed in M12
      prostate cancer cells. We have examined mac25/IGFBP-rP1 and 25.1 as potential
      molecular regulators in vitro of the NE-differentiation process in lung cancer.
      In a panel of SCLC and NSCLC cell lines, mac25/IGFBP-rP1 and 25.1 were expressed
      at higher levels in SCLC. An increase and sustained activation of adenosine 3',5'
      cyclic monophosphate (cAMP) levels induced NE-like differentiation in NSCLC cell
      lines, and a concomitant increase in the expression of mac25/IGFBP-rP1 and 25.1
      was observed during the cAMP-regulated differentiation of NCI-H157 cells,
      suggesting the involvement of these proteins. Furthermore, the collective
      overexpression of mac25/IGFBP-rP1 and 25.1 in NSCLC cells induced NE-like
      differentiation as early as 6 h postinfection. The present data suggest that
      mac25/IGFBP-rP1 and 25.1 may play a functional role in the NE differentiation of
      NSCLC cell lines and may provide a novel therapeutic target for treating lung
      cancers, in particular NSCLC with NE differentiation.

PMID- 16302003
TI  - Targeting cyclin D1, a downstream effector of INI1/hSNF5, in rhabdoid tumors.
AB  - Rhabdoid tumors (RTs) are aggressive and currently incurable pediatric
      malignancies. INI1/hSNF5 is a tumor suppressor biallelically inactivated in RTs.
      Our previous studies have indicated that cyclin D1 is a key downstream target of
      INI1/hSNF5 and genesis and/or survival of RTs in vivo is critically dependent on
      the presence of cyclin D1. In this report, we have tested the hypothesis that
      therapeutic targeting of cyclin D1 is an effective means of treating RTs. We
      found that RNA interference of cyclin D1 in rhabdoid cells was sufficient to
      induce G1 arrest and apoptosis. Furthermore, we found that pharmacological
      intervention with low micromolar concentrations of N-(4-hydroxyphenyl)retinamide
      (4-HPR), which downmodulates cyclin D1, induced G1 arrest and apoptosis in
      rhabdoid cell lines. 4-HPR in combination with 4-hydroxy-tamoxifen (4OH-Tam),
      synergistically inhibited survival as well as anchorage-dependent and 
      independent growth of rhabdoid cells and caused synergistic induction of cell
      cycle arrest and apoptosis. 4-HPR and tamoxifen exhibited synergistic growth
      inhibition of RTs in xenograft models in vivo. The effects of combination of
      drugs were correlated to the depletion of cyclin D1 levels both in in vitro and
      in vivo tumor models. These results demonstrate that 4-HPR and tamoxifen are
      effective chemotherapeutic agents for RTs. We propose that downmodulation of
      cyclin D1 is a novel and effective therapeutic strategy for RTs.

PMID- 16302004
TI  - Impact of dietary and lifestyle factors on the prevalence of hypertension in
      Western populations.
AB  - The impact of dietary and lifestyle factors on the prevalence of hypertension was
      quantified for Finland, Italy, The Netherlands, UK and USA. For this purpose, we
      combined data of blood pressure (BP) and risk factors distributions in these five
      countries with BP estimates from randomized controlled trials of dietary and
      lifestyle factors to obtain population attributable risk percentages (PAR%) for
      hypertension. Overweight made a substantial contribution to hypertension (PAR%:
      11-17%), as was the case for excessive sodium intake (9-17%), low potassium
      intake (4-17%), physical inactivity (5-13%), and low intake of fish oil (3-16%).
      PAR% were smaller for low calcium intake (2-8%), low magnesium intake (4-8%),
      excessive coffee consumption (1-9%) and excessive alcohol intake (2-3%). We
      conclude that diet and lifestyle have a major impact on hypertension in Western
      societies. The relative significance of different risk factors varies among
      populations, which is important for preventive strategies.

PMID- 16302005
TI  - Why and how to implement sodium, potassium, calcium, and magnesium changes in
      food items and diets?
AB  - The present average sodium intakes, approximately 3000-4500 mg/day in various
      industrialised populations, are very high, that is, 2-3-fold in comparison with
      the current Dietary Reference Intake (DRI) of 1500 mg. The sodium intakes
      markedly exceed even the level of 2500 mg, which has been recently given as the
      maximum level of daily intake that is likely to pose no risk of adverse effects
      on blood pressure or otherwise. By contrast, the present average potassium,
      calcium, and magnesium intakes are remarkably lower than the recommended intake
      levels (DRI). In USA, for example, the average intake of these mineral nutrients
      is only 35-50% of the recommended intakes. There is convincing evidence, which
      indicates that this imbalance, that is, the high intake of sodium on one hand and
      the low intakes of potassium, calcium, and magnesium on the other hand, produce
      and maintain elevated blood pressure in a big proportion of the population.
      Decreased intakes of sodium alone, and increased intakes of potassium, calcium,
      and magnesium each alone decrease elevated blood pressure. A combination of all
      these factors, that is, decrease of sodium, and increase of potassium, calcium,
      and magnesium intakes, which are characteristic of the so-called Dietary
      Approaches to Stop Hypertension diets, has an excellent blood pressure lowering
      effect. For the prevention and basic treatment of elevated blood pressure,
      various methods to decrease the intake of sodium and to increase the intakes of
      potassium, calcium, and magnesium should be comprehensively applied in the
      communities. The so-called 'functional food/nutraceutical/food-ceutical'
      approach, which corrects the mineral nutrient composition of extensively used
      processed foods, is likely to be particularly effective in producing immediate
      beneficial effects. The European Union and various governments should promote the
      availability and use of such healthier food compositions by tax reductions and
      other policies, which make the healthier choices cheaper than the conventional
      ones. They should also introduce and promote the use of tempting nutrition and
      health claims on the packages of healthier food choices, which have an increased
      content of potassium, calcium, and/or magnesium and a lowered content of sodium.
      Such pricing and claim methods would help the consumers to choose healthier food
      alternatives, and make composition improvements tempting also for the food
      industry.

PMID- 16302006
TI  - Effects of exercise, diet and their combination on blood pressure.
AB  - Epidemiological studies suggest an inverse relationship between physical activity
      or fitness and blood pressure. In a meta-analysis of 44 randomized controlled
      intervention trials, the weighted net change in conventional systolic/diastolic
      blood pressure in response to dynamic aerobic training averaged -3.4/-2.4 mmHg (P
      < 0.001). The effect on blood pressure was more pronounced in hypertensives than
      in normotensives. This type of training also lowered the blood pressure measured
      during ambulatory monitoring and during exercise. However, exercise appears to be
      less effective than diet in lowering blood pressure (P < 0.02), and adding
      exercise to diet does not seem to further reduce blood pressure.

PMID- 16302007
TI  - Hypertension prevention: from nutrients to (fortified) foods to dietary patterns.
      Focus on fatty acids.
AB  - Diet affects significantly the incidence and severity of cardiovascular diseases
      and fatty acid intake, in its qualitative as well as quantitative aspects, and
      influences several risk factors including cholesterol (total, LDL and HDL),
      triglycerides, platelet aggregation and blood pressure, as evidenced in the 2001
      WHO report. This review focuses on the qualitative concern of lipid intake, the
      various classes of fatty acids of the lipid fraction of the diet, saturated,
      monounsaturated and polyunsaturated, and their effects on blood pressure.
      Saturated fat have a bad file and several experimental studies in the rat showed
      a progressive increase in blood pressure in response to a highly saturated diet.
      Moreover, a highly saturated diet during gestation led to offspring which, when
      adults, presented a gender-related hypertension. The mechanism of this effect may
      be related to the polyunsaturated/saturated ratio (p/s). During the past 20
      years, trans fatty acids have been suspected of deleterious health effects, but
      the investigations have shown that these fatty acids display a biological
      behaviour close to that of saturated fatty acids (SFA). Moreover, epidemiological
      investigations did not confirm the relationship between trans fatty acids and
      cardiovascular pathology. Polyunsaturated fatty acids have been shown to exert a
      positive action on hypertension. This effect could be attributed to the
      alteration of the p/s, but mainly to the omega3 polyunsaturated fatty acids
      (PUFAs). The comparison of several animal models led to the conclusion that long
      chain omega3 PUFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA))
      can prevent the increase in blood pressure and reduce established hypertension,
      but the efficient dose remains an object of discussion. Moreover, the two long
      chain omega3 PUFAs, EPA and DHA, display specific effects, which vary with the
      aetiology of hypertension, because their mechanism of action is different. DHA
      acts on both blood pressure and heart function (heart rate and ECG) and
      interferes with the adrenergic function. Conversely, EPA, which is not
      incorporated in cardiac phospholipids, has no effect on the heart and its
      mechanism of action is largely unknown. Although it is accepted by the scientific
      community that the intake of EPA and DHA needs to be increased, we will have to
      discover new ways to do it, since marine products are the main source of these
      fatty acids, and this source is not inexhaustible.

PMID- 16302008
TI  - Hypertension, single sugars and fatty acids.
AB  - Macronutrients may induce various hemodynamic effects. In the fructose-fed rat
      blood pressure increase is associated with insulin resistance and enhanced
      sympathetic activity. In humans, oral glucose intake induces a slight and
      transient increase of blood pressure secondary to sympathetic activation. This
      increase may be higher in hypertensive subjects and followed by a significant
      fall in blood pressure in elderly subjects. Saturated fatty acid-enriched diet
      induces in male rats a significant increase in blood pressure related to
      sympathetic activation. Some observational and interventional studies suggest
      that n-3 polyunsaturated fatty-acids may reduce blood pressure in humans. Thus,
      both carbohydrates and fatty acid balance may contribute to blood pressure
      changes. The clinical relevance of these data should be evaluated in long-term
      trials, in particular in overweight and hypertensive subjects.

PMID- 16302009
TI  - Genetic association of ubiquilin with Alzheimer's disease and related
      quantitative measures.
AB  - The gene coding for ubiquilin 1 (UBQLN1) is located near a linkage peak on
      chromosome 9q22.2 and it also impacts the function of presenilin proteins
      involved in early-onset Alzheimer's disease (AD). Recently, genetic variation in
      UBQLN1 has been shown to affect the risk of AD in two independent family-based
      samples. The purpose of this study was to confirm the reported association in a
      large case-control sample and to also examine the association of UBQLN1 SNPs with
      quantitative measures of AD progression, namely age-at-onset (AAO), disease
      duration and Mini-Mental State Examination (MMSE) score. We examined the
      associations of three SNPs in the UBQLN1 gene (intron 6/A>C, intron 8/T>C and
      intron 9/A>G) in up to 978 LOAD cases and 808 controls. All SNPs were in
      significant linkage disequilibrium (P<0.0001). While modest significant
      associations were observed in the single-site regression analysis, 3-site
      haplotype analysis revealed significant associations (P<0.0001 for overall
      haplotype analysis). One common haplotype (H4) defined by intron 6/A-intron 8/C
      intron 9/G alleles was associated with AD risk and one less common haplotype (H5)
      defined by intron 6/C-intron 8/C-intron 9/A alleles was associated with
      protection. The adjusted odds ratios with potentially one and two copies of risk
      haplotype H4 were 1.5 (95% CI: 0.99-2.26; P=0.054) and 3.66 (95% CI: 1.43-9.39;
      P=0.007), respectively, and odds ratio for haplotype H5 carriers was 0.31 (95%
      CI: 0.10-0.95; P=0.0398). In addition to disease risk, the homozygosity of the
      risk haplotype was also associated with older AAO, longer disease duration and
      lower MMSE score. In summary, our data from a large case-control cohort indicate
      that genetic variation in the UBQLN1 gene has a modest effect on risk, AAO and
      disease duration of AD. Our haplotype data suggest the presence of additional
      putative functional variants either in the UBQLN1 gene or nearby genes and
      provide strong justification for additional work in this region on chromosome 9.

PMID- 16302010
TI  - Mapping of hippocampal gene clusters regulated by the amygdala to nonlinkage
      sites for schizophrenia.
AB  - A recent study using a 'partial' rodent model of schizophrenia has employed
      amygdalar activation to induce reported changes in the expression of hippocampal
      genes associated with metabolic and signaling pathways in response to amygdalar
      activation. The amygdalo-hippocampal pathway plays a central role in the
      regulation of the stress response and emotional learning. In the current study,
      we have performed a chromosome mapping analysis to determine whether genes
      showing changes in response to environmental stress may form clusters and, if so,
      whether they might show a topographical association with linkage sites for
      schizophrenia. When the hippocampal genes showing changes in expression were
      topographically mapped on specific rat chromosomes, significant clustering was
      observed on chromosomes 1, 4 and 8, although chromosome 1 showed the largest
      amount of clustering. When these same rodent genes were mapped to human
      chromosomes, most of the genes found on chromosome 1 in rat mapped to chromosome
      11 in human. The vast majority of the genes showing changes in regulation were
      excluded from known linkage sites for schizophrenia. Based on these findings, we
      postulate that environmental factors may contribute to the endophenotype for
      schizophrenia through the activation and/or deactivation of specific genetic
      clusters, ones that do not appear to be directly associated with susceptibility
      genes for this disorder.

PMID- 16302011
TI  - Characteristics and prevalence of the metabolic syndrome among three ethnic
      groups in Canada.
AB  - OBJECTIVE: To compare the characteristics and prevalence of the metabolic
      syndrome (MetS) among Native Indians, Inuit, and non-Aboriginal Canadians.
      METHODS: The study was based on four cross-sectional studies conducted in the
      late 1980s and early 1990s involving three ethnic groups living in contiguous
      regions in central Canada: Oji-Cree Indians from several reserves in northern
      Ontario and Manitoba, Inuit from the Keewatin region of the Northwest
      Territories, and non-Aboriginal Canadians (predominantly of European heritage) in
      the province of Manitoba. The MetS was identified among adult subjects according
      to the National Cholesterol Education Program (NCEP) definition. Prevalence rates
      were standardized to the 1991 Canadian national population. RESULTS: The age
      standardized prevalence of the MetS varied by ethnic group, ranging from as high
      as 45% among Native Indian women to as low as 8% among Inuit men. Compared with
      Canadians of European origin, Indians had a worse metabolic profile, while Inuit
      had a better metabolic profile except for a high rate of abdominal obesity. The
      NCEP criteria in identifying individuals with the MetS were compared to those of
      the World Health Organization (WHO) in a subset of subjects with the requisite
      laboratory data. There was moderate agreement between the NCEP and WHO
      definitions, with a kappa value of 0.63 (95% confidence interval 0.56-0.70).
      CONCLUSIONS: The results indicate that the MetS is prevalent in diverse ethnic
      groups in Canada but varies in the pattern of phenotypic expression. Given the
      diverse nature of these populations, careful consideration should be given to
      developing culturally appropriate community-based prevention strategies aimed at
      reducing the frequency of this syndrome.

PMID- 16302012
TI  - Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans.
AB  - OBJECTIVE: Oxidative stress may be the unifying mechanism underlying the
      development of comorbidities in obesity. Evidence suggests that a clustering of
      sources of oxidative stress exists in obesity: hyperglycemia, hyperleptinemia,
      increased tissue lipid levels, inadequate antioxidant defenses, increased rates
      of free radical formation, enzymatic sources within the endothelium, and chronic
      inflammation. METHOD: This review provides a summary of the available evidence on
      systemic oxidative stress in humans and specific metabolic pathways by which
      obesity may elevate systemic oxidant stress. The authors suggest possible methods
      of reducing oxidative stress such as antioxidant supplementation, caloric
      restriction and/or physical activity and surgical intervention to combat free
      radicals and reduce adipose tissue. RESULTS: Obesity is associated with oxidative
      stress and can be reduced with weight loss (regardless of exercise or surgery
      induced weight loss), caloric restriction or antioxidant rich diets. CONCLUSION:
      Oxidative stress levels are elevated in human obesity, and these levels are
      modifiable with various lifestyle modifications and surgical interventions.

PMID- 16302013
TI  - The definition of weight maintenance.
AB  - There is currently no consensus on the definition of weight maintenance in
      adults. Issues to consider in setting a standard definition include expert
      opinion, precedents set in previous studies, public health and clinical
      applications, comparability across body sizes, measurement error, normal weight
      fluctuations and biologic relevance. To be useful, this definition should
      indicate an amount of change less than is clinically relevant, but more than
      expected from measurement error or fluctuations in fluid balance under normal
      conditions. It is an advantage for the definition to be graded by body size and
      to be easily understood by the public as well as scientists. Taking all these
      factors into consideration, the authors recommend that long-term weight
      maintenance in adults be defined as a weight change of <3% of body weight.

PMID- 16302014
TI  - Obesity and depression: results from the longitudinal Northern Finland 1966 Birth
      Cohort Study.
AB  - OBJECTIVE: To examine the association between body size and depression in a
      longitudinal setting and to explore the connection between obesity and depression
      in young adults at the age of 31 years. DESIGN: This study forms part of the
      longitudinal Northern Finland 1966 Birth Cohort Study (N = 12,058). The follow-up
      studies were performed at 14 and 31 years. Data were collected by postal inquiry
      at 14 years and by postal inquiry and clinical examination at 31 years. SUBJECTS:
      A total of 8,451 subjects (4,029 men and 4,422 women) who gave a written informed
      consent and information on depression by three depression indicators at 31 years.
      MEASUREMENTS: Body size at 14 (body mass index (BMI) and 31 (BMI and waist-to-hip
      ratio (WHR)) years and depression at 31 years by three different ways: depressive
      symptoms by the HSCL-25-depression questionnaire (HSCL-25), the use of
      antidepressants and self-reported physician-diagnosed depression. RESULTS:
      Obesity at 14 years associated with depressive symptoms at 31 years; among male
      subjects using the cutoff point 2.01 in the HSCL-25 (adjusted odds ratio (OR)
      1.97, 95% CI 1.06-3.68), among female subjects using the cutoff point 1.75
      (adjusted OR 1.64, 95% CI 1.16-2.32). Female subjects who were obese both at
      baseline and follow-up had depressive symptoms relatively commonly (adjusted OR
      1.40, 95% CI 1.06-1.85 at cutoff point 1.75); a similar association was not found
      among male subjects. The proportion of those who used antidepressants was 2.17
      fold higher among female subjects who had gained weight compared to female
      subjects who had stayed normal-weighted (adjusted OR 2.17, 95% CI 1.28-3.68). In
      the cross-sectional analyses male subjects with abdominal obesity (WHR >or=85th
      percentile) had a 1.76-fold risk of depressive symptoms using the cutoff 2.01 in
      the HSCL-25 (adjusted OR 1.76, 95% CI 1.08-2.88). Abdominally obese male subjects
      had a 2.07-fold risk for physician-diagnosed depression (adjusted OR 2.07, 95% CI
      1.23-3.47) and the proportion of those who used antidepressants was 2.63-fold
      higher among obese male subjects than among male subjects without abdominal
      obesity (adjusted OR 2.63, 95% CI 1.33-5.21). Abdominal obesity did not associate
      with depression in female subjects. CONCLUSION: Obesity in adolescence may be
      associated with later depression in young adulthood, abdominal obesity among male
      subjects may be closely related to concomitant depression, and being
      overweight/obese both in adolescence and adulthood may be a risk for depression
      among female subjects.

PMID- 16302015
TI  - Relationships among acylation stimulating protein, adiponectin and complement C3
      in lean vs obese type 2 diabetes.
AB  - OBJECTIVE: The purpose of this study was to determine the relationships between
      adipocyte hormones acylation stimulating protein (ASP), adiponectin, complement
      C3 (C3) (ASP precursor) and insulin, C-reactive protein (CRP), lipid profiles and
      insulin resistance in lean vs obese type 2 diabetes subjects. SUBJECTS: Lean type
      2 diabetes subjects (DL n = 27) vs obese type 2 diabetes subjects (DO n = 55)
      were compared to age-matched nondiabetic groups (Obese, OB n = 55 and control,
      CTL n = 50). RESULTS: The DO group demonstrated significant increases in plasma
      ASP and C3 with decreases in plasma adiponectin as compared to CTL.
      Interestingly, these increases in ASP and C3 were as high, or greater, in the DL
      group in spite of normal weight. By contrast adiponectin in the DL group was
      comparable to CTL, in spite of marked insulin resistance. C3 correlated with
      insulin, glucose and homeostasis model assessment of insulin resistance (HOMA
      IR); ASP correlated with body mass index (BMI), glucose, insulin and plasma lipid
      parameters (non-esterified fatty acids (NEFA), triglyceride, cholesterol and
      apolipoprotein B). Adiponectin correlated with BMI, glucose, NEFA, triglyceride,
      high-density lipoprotein cholesterol and apolipoprotein A1 but not HOMA-IR, ASP
      or C3. CRP correlated only with HOMA-IR. CONCLUSION: Increased ASP and C3 are
      both associated with diabetes and related lipid factors but are not regulated
      coordinately. Adiponectin appears to be more closely related to body size
      (decreased in obese subjects) than insulin resistance in these subjects.

PMID- 16302016
TI  - Effects of the biliopancreatic diversion on energy balance in the rat.
AB  - OBJECTIVE: This study was carried out to determine the effects of the
      biliopancreatic diversion (BPD), a bariatric surgery applied to the treatment of
      morbidly obese humans, on energy balance in rats. METHODS: BPD was performed on a
      group of male Wistar rats. Body weight and food intake were measured daily
      throughout the study. Feces were also collected to assess energy losses and the
      determination of digestible energy. Energy expenditure and body composition were
      also determined for the 50-day length of the protocol. On the day of killing, the
      brain, the entire intestinal tract and white and brown adipose tissues were
      collected and weighed. Expression of neuropeptide Y (NPY) and agouti-related
      protein (AgRP) in the ARC nucleus were assessed by in situ hybridization.
      RESULTS: Marked changes in the regulation of energy balance were observed in the
      BPD-operated rats. A decrease in digestible energy and food intake coupled with
      an increase in the fecal energy density and protein fecal energy led to an
      important weight loss in the BPD-operated rats. This weight loss was observed in
      the loss of fat mass (specifically the white epididymal, inguinal,
      retroperitoneal and brown adipose tissues). The rats modified their food intake
      pattern to be able to potentially eat more during the entire day. An increase in
      the surfaces of all intestinal structures (muscular and mucosal layers) was
      observed in the BPD-operated rats. The NPY and AgRP expression in the brain were
      both shown to be greater in the BPD-operated rats than in the control animals. At
      the beginning of the study, the surgery led to an energy expenditure decrease,
      which, however, did not persist throughout the study despite the fact that BPD
      operated rats exhibited persistent lower fat free masses. CONCLUSION: BPD led to
      a noticeable reduction in weight and fat gains in rats, which was in large part
      owing to a decrease in digestible energy intake led to by the gastrectomy, the
      intestinal malabsorption inherent to the surgery and to potentially a
      thermogenesis stimulation that occurred in the second end of the study. The
      reduction in energy gain occurs despite adaptations to thwart the intestinal
      malabsorption and the hunger signals from the central nervous system.

PMID- 16302017
TI  - Depressive mood and obesity in US adults: comparison and moderation by sex, age,
      and race.
AB  - OBJECTIVE: Sustained depressive mood is a gateway symptom for a major depressive
      disorder. This paper investigated whether the association between depressive mood
      and obesity differs as function of sex, age, and race in US adults after
      controlling for socio-economic variables of martial status, employment status,
      income level and education level. METHODS: A total of 44,800 nationally
      representative respondents from the 2001 Behavioral Risk Factor Surveillance
      Survey were studied. Respondents were classified as having experienced a
      depressive mood if they felt sad, blue, or depressed at least for 1 week in the
      previous month. The depressive mood was operationalized in terms of duration and
      sustenance, both defined based on number of days with depressive mood: 7+ and 14+
      days. Age groups were classified as young (18-64 years) and old (65+ years).
      Obesity status was classified as: not overweight/obese (BMI<25); overweight
      (25<or=BMI<30); obese (BMI>or=30). RESULTS: Prevalence of prior-month depressive
      mood was 14.3 and 7.8% for 7+ and 14+ days, respectively. Controlling for race
      and socio-economic variables, both young overweight and obese women were
      significantly more likely to have experienced depressive mood than
      nonoverweight/nonobese women. Young overweight, but not obese, men were
      significantly more likely to have experienced depressive mood than
      nonoverweight/nonobese men. Young obese women were also significantly more likely
      to have a sustained depressive mood than nonoverweight/nonobese women. For old
      respondents, depressive mood and its sustenance were not associated with obesity
      in either sex. DISCUSSION: The relationship between the depressive mood and
      obesity is dependent upon gender, age, and race. Young obese women, Hispanics in
      particular, are much more prone to depressive mood than nonobese women. Future
      studies testing associations between depression and obesity should be sensitive
      to the influence of these demographic and socio-economic variables.

PMID- 16302019
TI  - Calcium and weight loss.

PMID- 16302022
TI  - Pharmacogenetics and the concept of individualized medicine.
AB  - Adverse drug reaction in patients causes more than 2 million hospitalizations
      including 100,000 deaths per year in the United States. This adverse drug
      reaction could be due to multiple factors such as disease determinants,
      environmental and genetic factors. In order to improve the efficacy and safety
      and to understand the disposition and clinical consequences of drugs, two rapidly
      developing fields--pharmacogenetics (focus is on single genes) and
      pharmacogenomics (focus is on many genes)--have undertaken studies on the genetic
      personalization of drug response. This is because many drug responses appear to
      be genetically determined and the relationship between genotype and drug response
      may have a very valuable diagnostic value. Identification and characterization of
      a large number of genetic polymorphisms (biomarkers) in drug metabolizing enzymes
      and drug transporters in an ethnically diverse group of individuals may provide
      substantial knowledge about the mechanisms of inter-individual differences in
      drug response. However, progress in understanding complex diseases, its negative
      psychosocial consequences, violation of privacy or discrimination, associated
      cost and availability and its complexity (extensive geographic variations in
      genes) may become potential barriers in incorporating this pharmacogenetic data
      in risk assessment and treatment decisions. In addition, it requires increased
      enthusiasm and education in the clinical community and an understanding of
      pharmacogenetics itself by the lay public. Although individualized medications
      remain as a challenge for the future, the pharmacogenetic approach in drug
      development should be still continued. If it becomes a reality, it delivers
      benefits to improve public health and allow genetically subgroup diseases thereby
      avoiding adverse drug reactions (by knowing in advance who should be treated with
      what drug and how).

PMID- 16302021
TI  - Response to fluoxetine and serotonin 1A receptor (C-1019G) polymorphism in Taiwan
      Chinese major depressive disorder.
AB  - Serotonin systems appear to play a key role in the pathogenesis of major
      depression and the therapeutic mechanisms of antidepressants. The firing rate of
      dorsal raphe serotonergic neurons is controlled by somatodendritic 5
      hydroxytryptamine 1A (HTR1A) autoreceptors, and desensitization of these
      receptors is implicated in the antidepressant mechanism of selective serotonin
      reuptake inhibitors. We tested whether a functional polymorphism (C-1019G) in the
      promoter region of the HTR1A gene and serotonin-related genetic variants are
      related to fluoxetine antidepressant effect. We genotyped the HTR1A C-1019G
      polymorphism as well as polymorphisms in the serotonin transporter gene-linked
      polymorphic region (SERTPR), variable-number tandem-repeat polymorphisms in
      intron 2 (STin2) of the serotonin transporter gene, serotonin 2A receptor
      (T102C), tryptophan hydroxylase (A218C), and G-protein beta3 subunit (C825T) in
      224 Chinese patients from southern Taiwan with major depression, who accepted 4
      week fluoxetine treatment and therapeutic evaluation. Our results demonstrated
      that the HTR1A -1019C/C carriers (P=0.009) and SERTPR l/l carriers (P<0.001)
      showed a better response to fluoxetine, while other polymorphisms were not
      associated with fluoxetine therapeutic response. The major limitation of this
      study is the lack of a placebo control. Future prospective study with placebo
      control may help to predict and individualize antidepressant treatment.

PMID- 16302023
TI  - Does in vitro replicative senescence of human CD8+ cells reflect the phenotypic
      changes observed during in vivo ageing?
AB  - Immunosenescence is viewed as a remodeling process with the exhaustion of naive T
      cells and filling up of the immunological space with memory cells. In this study
      some phenotypic changes of CD8(+) human cells during in vivo ageing were compared
      with those observed in long term cultures of lymphocytes derived from cord blood
      or from peripheral blood from donors of different age. Both in vivo and in vitro
      a significant decrease of the fraction of CD8(+)CD28(+) cells was observed.
      Comparing the proportions of other T cell subpopulations (the CD4/CD8(+) ratio,
      CD56, CD57, CD27) made it possible to conclude that replicative senescence in
      vitro partially reflects in vivo ageing.

PMID- 16302024
TI  - Modulation of ERK1/2 activity is crucial for sphingosine-induced death of glioma
      C6 cells.
AB  - In this study the contribution of the ERK1/2 pathway to sphingosine-induced death
      and morphological changes of the actin cytoskeleton in glioma C6 cells was
      investigated. Surprisingly, the level of ERK1/2 phosphorylation does not change
      after incubation of cells with sphingosine. Despite this, sphingosine induces
      rounding and detachment of cells without formation of apoptotic bodies. To shed
      light on this process, a specific inhibitor of ERK1/2 phosphorylation, U0126, was
      used. Cells incubated simultaneously with sphingosine and U0126 not only
      detached, but also exhibited formation of apoptotic-like blebs. These data
      suggest that during sphingosine-induced glioma C6 cell death apoptotic blebbing
      is dependent on ERK1/2 signalling and occurs only when ERK1/2 activity is
      decreased or abolished.

PMID- 16302025
TI  - Expression of recombinant forms of human 21.5 kDa myelin basic protein and
      proteolipid protein in CHO cells.
AB  - MBP and PLP are major structural protein components of myelin. Both proteins play
      a functional role in formation of myelin sheath and in maintenance of its
      compaction. Immune responses to MBP and PLP have been implicated in the
      pathogenesis of multiple sclerosis (MS), an auto-immune disease of the central
      nervous system. Recombinant forms of both proteins isolated and purified from
      bacterial or insect cell systems are commonly used to study the specificity of
      auto-response in MS. We have prepared recombinant forms of MBP and PLP stably
      expressed in CHO cells. Several clones with proper cytoplasmic MBP or surface PLP
      localization were obtained and characterized by flow cytometry and indirect
      immunostaining. CHO cells expressing the recombinant forms of MBP and PLP can be
      very useful in studies on the autoimmune mechanism of MS.

PMID- 16302026
TI  - Effect of aging and oxidative/genotoxic stress on poly(ADP-ribose) polymerase-1
      activity in rat brain.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1, EC 2.4.2.30), a DNA-bound enzyme, plays a
      key role in genome stability, but after overactivation can also be responsible
      for cell death. The aim of the present study was to investigate PARP-1 activity
      in the hippocampus, brain cortex, striatum and cerebellum in adult (4 months) and
      aged (24 months) specific pathogen free Wistar rats and to correlate it with PARP
      1 protein level and p53 expression. Moreover, the response of PARP-1 in adult and
      aged hippocampus to oxidative/genotoxic stress was evaluated. Our data indicated
      a statistically significant enhancement of PARP-1 activity in aged hippocampus
      and cerebral cortex comparing to adults without statistically significant changes
      in PARP-1 protein level. The expression of p53 mRNA was elevated in all aged
      brain parts with the exception of the cerebral cortex. Our data suggest that
      enhancement of PARP-1 activity and p53 expression in aged brain may indicate
      higher DNA damage. Our data also indicate that during excessive
      oxidative/genotoxic stress there is no response of PARP-1 activity in aged
      hippocampus in contrast to a significant enhancement of PARP-1 activity in adults
      which may have important consequences for the physiology and pathology of the
      brain.

PMID- 16302027
TI  - Isolation and expression pattern of RGS21 gene, a novel RGS member.
AB  - Regulators of G-protein signaling (RGS) proteins are known for the RGS domain
      that is composed of a conserved stretch of 120 amino acids, which binds directly
      to activated G-protein alpha subunits and acts as a GTPase-activating protein
      (GAP), leading to their deactivation and termination of downstream signals. In
      this study, a novel human RGS cDNA (RGS21), 1795 bp long and encoding a 152-amino
      acid polypeptide, was isolated by large-scale sequencing analysis of a human
      fetal brain cDNA library. Unlike other RGS family members, RGS21 gene has no
      additional domain/motif and may represent the smallest known member of RGS
      family. It may belong to the B/R4 subfamily, which suggests that it may serve
      exclusively as a negative regulator of alphai/o family members and/or alphaq/11.
      PCR analysis showed that RGS21 mRNA was expressed ubiquitously in the 16 tissues
      examined, implying general physiological roles.

PMID- 16302028
TI  - Tissue distribution of a menthyl-conjugated oligodeoxyribonucleotide antisense to
      PAI-1 mRNA.
AB  - The inhibitory effect of numerous analogues of PO-16, an
      hexadecadeoxyribonucleotide antisense to sequences -22 to -17 of PAI-1 mRNA
      coding for a fragment of the signal peptide, on the expression of PAI-1 in
      endothelial cells, and physiological consequences of the subsequently reduced PAI
      1 activity tested in vitro and in vivo, were described in our previous studies.
      Of particular interest was PO-16 5'-O-conjugated with menthyl phosphorothioate
      (MPO-16R). In this work, tissue localisation of MPO-16R labelled with [(35)S]
      phosphorothioate at the 3'-end, was determined. [(35)S]MPO-16R and control
      [(35)S]MPO-16R-SENSE oligonucleotides were administered intravenously into 22
      rats and organ distribution of the labelled bioconjugates was assessed after 24
      and 48 h. For this purpose, tissue sections were subjected to autoradiography,
      and quantitated by liquid scintillation after solubilisation. Overall clearance
      of radioactivity was already seen after 24 h, with the radioactivity recovered
      mainly in the kidney and liver. A smaller fraction of radioactivity was also
      retained in the spleen and heart. The kidney concentration of the labelled probe
      was higher than that of liver by 50%. The distribution of PAI-1 mRNA in untreated
      rat kidney, liver, spleen and heart established by two independent techniques:
      Ribonuclease Protection Assay and Real-Time PCR, shows the same pattern as that
      observed for [(35)S]MPO-16R antisense.

PMID- 16302029
TI  - Calling a spade a spade: meaningful definitions of health conditions.

PMID- 16302030
TI  - Breaking the vicious circle of determinants and consequences of harmful alcohol
      use.

PMID- 16302031
TI  - Getting health care to vulnerable communities.

PMID- 16302032
TI  - Fighting genital mutilation in Sierra Leone.

PMID- 16302033
TI  - Can a new UN emergency fund help southern Africa?

PMID- 16302034
TI  - Poor countries need help to fight bird flu.

PMID- 16302035
TI  - WHO assists with relief efforts in south Asia.

PMID- 16302037
TI  - Alcohol consumption and increased mortality in Russian men and women: a cohort
      study based on the mortality of relatives.
AB  - OBJECTIVE: To examine the relations between frequency of alcohol consumption and
      of binge drinking and adult mortality in Russian men and women. METHODS: Using
      modified indirect demographic techniques, a convenience cohort was constructed
      based on survey respondents' information about their close relatives. A random
      sample general population of the Russian Federation of 7172 respondents (response
      rate 61%) provided information on 10 475 male and 3129 female relatives,
      including age, vital status, and frequency of alcohol consumption and binge
      drinking. These relatives formed the cohort analysed in this report. The outcome
      measure was all-cause mortality after the age of 30 years. FINDINGS: There was a
      strong linear relation between frequency of drinking and of binge drinking and
      all-cause mortality in men; after controlling for smoking and calendar period of
      birth, the relative risk of death in daily drinkers compared to occasional
      drinkers was 1.52 (95% confidence interval (CI) 1.33-1.75). Male binge drinkers
      had higher mortality than drinkers who did not binge, which persisted after
      adjustment for drinking frequency (adjusted relative risk 1.09, 95% CI 1.00
      1.19). In women, the increased mortality was confined to a small group of those
      who binged at least once a month (adjusted relative risk 2.68, 95% CI 1.54-4.66).
      CONCLUSION: The results suggest a positive association between alcohol and
      mortality in the Russian Federation. There was no evidence for the protective
      effect of drinking seen in western populations. Alcohol appears to have
      contributed to the high long-term mortality rates in Russian men, but it is
      unlikely to be a major cause of female mortality.

PMID- 16302038
TI  - WHO study on Prevention of REcurrences of Myocardial Infarction and StrokE (WHO
      PREMISE).
AB  - OBJECTIVE: To determine the extent of secondary prevention of coronary heart
      disease (CHD) and cerebrovascular disease (CVD) in low- and middle-income
      countries. METHODS: A descriptive cross-sectional survey of a sample of 10 000
      CHD (85.2%) and CVD (14.8%) patients (6252 men; 3748 women) was conducted over 6
      months in geographically defined areas. The mean age was 59.2 years (standard
      deviation (SD), 10.8). Consecutive patients were recruited from a stratified
      random sample of primary, secondary and tertiary care facilities in defined areas
      in 10 countries (Brazil, Egypt, India, Indonesia, Islamic Republic of Iran,
      Pakistan, Russian Federation, Sri Lanka, Tunisia and Turkey). The main outcome
      measures were levels of lifestyle and physiological risk factors, and the use of
      drugs for secondary prevention of CHD and CVD. FINDINGS: Approximately 82%, 89%
      and 77% of patients were aware of the cardiovascular benefits of quitting
      smoking, a heart-healthy diet and regular physical activity, respectively. About
      half (52.5%) engaged in less than 30 minutes of physical activity per day, 35%
      did not follow a heart-healthy diet and 12.5 % were current tobacco users. Blood
      pressure had been measured in 93.8% (range 71-100%), blood cholesterol in 85.5%
      (range 29-97%) and blood sugar in 75.5% (range 65-99%) in the preceding 12
      months. The proportions who had received medications among CHD and CVD patients
      were: aspirin, 81.2%, 70.6%; beta-blockers, 48.1%, 22.8%; angiotensin-converting
      enzyme inhibitor, 39.8%, 37.8%; statins, 29.8%, 14.1%, respectively. About one
      fifth of patients with CHD had undergone revascularization. CONCLUSION: A
      significant proportion of patients did not receive appropriate medications. About
      47% of patients had at least two or more modifiable risk factors (smoking,
      physical inactivity, hypertension, diabetes or hypercholesterolaemia). There are
      considerable missed opportunities for prevention of recurrences in those with
      established CVD in low- and middle-income countries.

PMID- 16302039
TI  - Role of socioeconomic markers and state prohibition policy in predicting alcohol
      consumption among men and women in India: a multilevel statistical analysis.
AB  - OBJECTIVE: To investigate the independent contribution of individual
      socioeconomic markers and state prohibition policy on alcohol consumption among
      men and women in India. METHODS: The study used a multilevel cross-sectional
      analysis of alcohol consumption from the 1998-1999 Indian national family health
      survey of 301 984 adult individuals in 92 447 households in 3215 villages in 440
      districts in 26 states, stratified by sex. FINDINGS: Men with no education were
      more likely to consume alcohol that those with a post graduate education (OR,
      2.28; 95% CI, 2.08-2.50). Unlike men, women showed a U-shaped association between
      education and alcohol consumption. Men and women living in households at the
      lowest standard-of-living quintile were more likely to consume alcohol (OR, 1.92;
      95% CI, 1.81-2.03, and OR, 2.72, 95% CI, 2.18-3.39), respectively, than those
      classified as living in the top quintile. Members of scheduled tribes and castes
      and other backward classes were more likely to consume alcohol than members of
      other caste groups. There was no difference in alcohol consumption between men
      from states that were not under prohibition (OR, 1.36; 95% CI 0.69-2.03) and
      those that were. By contrast, states not under prohibition has higher alcohol use
      by women (OR, 3.04, 95% CI, 1.59-4.48) than those under partial or complete
      prohibition. CONCLUSION: Caste, education and standard of living independently
      influence alcohol use in India. Prohibition policies appear to have little effect
      on alcohol use by men, but may reduce the proportion of women who consume
      alcohol. The socioeconomic patterning of health behaviours is likely to feed
      substantially into inequalities in health outcomes. Further investigation is
      required to understand how social and cultural factors in more localized contexts
      (e.g. districts) influence alcohol consumption.

PMID- 16302040
TI  - Socioeconomic inequality in infant mortality in Iran and across its provinces.
AB  - OBJECTIVE: To measure the socioeconomic inequality in infant mortality in Iran
      (the Islamic Republic of Iran). METHODS: We analysed data from the provincially
      representative Demographic and Health Survey, which was done in Iran in 2000. We
      used a dichotomous hierarchical ordered probit model to develop an indicator of
      socioeconomic status of households. We assessed the inequality in infant
      mortality by using the odds ratio of infant mortality between the lowest and
      highest socioeconomic quintiles at both the provincial and national levels, and
      the concentration index, an inequality measure based on the entire socioeconomic
      distribution. RESULTS: We found a decreasing trend in the infant mortality rate
      in relation to socioeconomic quintiles. The poorest to richest odds ratio was
      2.34 (95% CI = 1.78-3.09). The concentration index of infant mortality in Iran
      was -0.1789 (95% CI = -0.2193--0.1386). Furthermore, the inequality of infant
      mortality between the lowest and highest quintiles was significant and favoured
      the better-off in most of the provinces. However, this inequality varied between
      provinces. CONCLUSION: Socioeconomic inequality in infant mortality favours the
      better-off in the country as a whole and in most of its provinces, but the degree
      of this inequality varies between the provinces. As well as its national average,
      it is important to consider the provincial distribution of this indicator of
      population health.

PMID- 16302041
TI  - Differences in willingness to pay for artemisinin-based combinations or
      monotherapy: experiences from the United Republic of Tanzania.
AB  - OBJECTIVE: The cost of combination treatment is thought to be one of the greatest
      barriers to their deployment, but this has not been tested directly. Estimates of
      willingness to pay were compared across four drug combinations used to treat
      Tanzanian children with uncomplicated malaria. The reasons behind respondents'
      valuations and the effect of socioeconomic status on willingness to pay were
      explored. METHODS: One hundred and eighty mothers whose children had been
      recruited into a recently completed randomized effectiveness trial of amodiaquine
      + artesunate (AQ+AS), amodiaquine + sulfadoxine-pyrimethamine (AQ+SP), artemether
      lumefantrine (coartemether) and amodiaquine monotherapy (AQ) were interviewed
      about their willingness to pay for these drugs two weeks after treatment.
      Estimates of willingness to pay were elicited with the bidding game technique.
      FINDINGS: A significant difference was detected in the mean amounts respondents
      were willing to pay, with those who received AQ+AS willing to pay the most,
      followed by co-artemether, AQ+SP and finally AQ. The amounts patients' mothers
      were willing to pay for the artemisinin-based combinations, however, fell well
      short of the market costs. Socioeconomic status was not found to have a
      statistically significant effect on mean willingness to pay scores for any
      treatment group. CONCLUSION: This study shows that families who live in an area
      in which drug resistance to monotherapy is very high are willing to pay more for
      more effective artemisinin-based combination therapies. These amounts, however,
      are nowhere near the real costs of delivering the new drugs. Only with subsidies
      will artemisinin-based combination therapies realistically have any impact.

PMID- 16302042
TI  - A new definition of drowning: towards documentation and prevention of a global
      public health problem.
AB  - Drowning is a major global public health problem. Effective prevention of
      drowning requires programmes and policies that address known risk factors
      throughout the world. Surveillance, however, has been hampered by the lack of a
      uniform and internationally accepted definition that permits all relevant cases
      to be counted. To develop a new definition, an international consensus procedure
      was conducted. Experts in clinical medicine, injury epidemiology, prevention and
      rescue from all over the world participated in a series of "electronic"
      discussions and face-to-face workshops. The suitability of previous definitions
      and the major requirements of a new definition were intensely debated. The
      consensus was that the new definition should include both cases of fatal and
      nonfatal drowning. After considerable dialogue and debate, the following
      definition was adopted: "Drowning is the process of experiencing respiratory
      impairment from submersion/immersion in liquid." Drowning outcomes should be
      classified as: death, morbidity, and no morbidity. There was also consensus that
      the terms wet, dry, active, passive, silent, and secondary drowning should no
      longer be used. Thus a simple, comprehensive, and internationally accepted
      definition of drowning has been developed. Its use should support future
      activities in drowning surveillance worldwide, and lead to more reliable and
      comprehensive epidemiological information on this global, and frequently
      preventable, public health problem.

PMID- 16302043
TI  - Treatment of tuberculosis: present status and future prospects.
AB  - Over recent years, tuberculosis (TB) and disease caused by human immunodeficiency
      virus (HIV) have merged in a synergistic pandemic. The number of new cases of TB
      is stabilizing and declining, except in countries with a high prevalence of HIV
      infection. In these countries, where HIV is driving an increase in the TB burden,
      the capacity of the current tools and strategies to reduce the burden has been
      exceeded. This paper summarizes the current status of TB management and describes
      recent thinking and strategy adjustments required for the control of TB in
      settings of high HIV prevalence. We review the information on anti-TB drugs that
      is available in the public domain and highlight the need for continued and
      concerted efforts (including financial, human and infrastructural investments)
      for the development of new strategies and anti-TB agents.

PMID- 16302044
TI  - The Public Health Act of 1848.

PMID- 16302045
TI  - An Act for promoting the Public Health. [31st August 1848].

PMID- 16302046
TI  - Successful sanitation promotion must recognize the use of latrine wastes in
      agriculture--the example of Viet Nam.

PMID- 16302047
TI  - Infant feeding in the context of HIV-positive mothers.

PMID- 16302048
TI  - Exclusive breastfeeding recommendation unchanged.

PMID- 16302050
TI  - Exclusive breastfeeding and postnatal transmission of HIV.

PMID- 16302052
TI  - [Women's mental health: what don't we know?].

PMID- 16302053
TI  - [Anxiety disorders in women: does gender matter to treatment?].
AB  - Women have a substantially higher risk of developing lifetime anxiety disorders
      compared with men. In addition, research evidence has generally observed an
      increased symptom severity, chronic course, and functional impairment in women
      with anxiety disorders in comparison to men. However, the reasons for the
      increased risk in developing an anxiety disorder in women are still unknown and
      have yet to be adequately investigated. Evidence from various studies has
      suggested that genetic factors and female reproductive hormones may play
      important roles in the expression of these gender differences. The significant
      differences in onset and course of illness observed in men and women diagnosed
      with anxiety disorders warrants investigations into the need of differential
      treatment; however, evidence of gender differences in treatment response to
      different anxiety disorders are varying and remain largely inconclusive. This
      article reviews the prevalence, epidemiology, and phenomenology of the major
      anxiety disorders in women, as well as the implications of such differences for
      treatment.

PMID- 16302054
TI  - [Domestic violence, alcohol and substance abuse].
AB  - Domestic violence and substance abuse are common in primary care patients.
      Although these problems are associated with severe physical and psychological
      sequelae, they are often undiagnosed. This article provides an overview of the
      prevalence of these problems, the health-related consequences for adults,
      children and elderly, as well as the challenges for clinicians in screening,
      assessment and referral.

PMID- 16302055
TI  - [Postpartum depression: we know the risks, can it be prevented?].
AB  - In the past 20 years, there has been increasing recognition that for some women,
      pregnancy may be burdened with mood problems, in particular depression, that may
      impact both mother and child. With identification of risk factors for postpartum
      depression and a growing knowledge about a biologic vulnerability for mood change
      following delivery, research has accumulated on attempts to prevent postpartum
      depression using various psychosocial, psychopharmacologic, and hormonal
      strategies. The majority of psychosocial and hormonal strategies have shown
      little effect on postpartum depression. Notwithstanding, results from preliminary
      trials of interpersonal therapy, cognitive-behavioural therapy, and
      antidepressants indicate that these strategies may be of benefit. Information on
      prevention of postpartum depression using dietary supplements is sparse and the
      available evidence is inconclusive. Although a few studies show promising
      results, more rigorous trials are required. The abounding negative evidence in
      the literature indicates that postpartum depression cannot be easily prevented,
      yet.

PMID- 16302056
TI  - [Trauma & the reproductive lifecycle in women].
AB  - Women are at significantly higher risk for developing post-traumatic stress
      disorder (PTSD) than men, resulting in increased psychosocial burden and
      healthcare related costs. Recent research has shown complex interactions between
      the impact of traumatic experiences, and the reproductive lifecycle in women. For
      example, women suffering from premenstrual dysphoric disorder (PMDD) who also
      report a history of sexual or physical abuse are more likely to present with
      different neuroendocrine reactivity to stressors, when compared to premenstrual
      dysphoric disorder subjects without prior history of trauma or abuse or non
      premenstrual dysphoric disorder subjects. In addition, women with a history of
      abuse or trauma may experience re-emergence of symptoms during pregnancy. Lastly,
      females who experience miscarriage may present with even higher prevalence rates
      of post-traumatic stress disorder symptoms. In this manuscript we examine the
      existing data on gender differences in post-traumatic stress disorder, with
      particular focus on psychological and physiological factors that might be
      relevant to the development of symptoms after exposure to traumatic events
      associated with the reproductive life cycle. Current options available for the
      treatment of such symptoms, including group and counselling therapies and
      debriefing are critically reviewed.

PMID- 16302057
TI  - [Women's Mental Health in Brazil: clinical challenges and perspectives in
      research].
AB  - Women's Mental Health in Brazil remains underserved due to the lack of
      specialized clinical centers and poor research training or productivity.
      Nonetheless, there have been some promising initiatives over the last two decades
      to integrate gynecologic and mental health services and provide more
      multidisciplinary clinical care. This paper reviews such initiatives and
      discusses their strengths and pitfalls.

PMID- 16302058
TI  - The use of biodiversity as source of new chemical entities against defined
      molecular targets for treatment of malaria, tuberculosis, and T-cell mediated
      diseases--a review.
AB  - The modern approach to the development of new chemical entities against complex
      diseases, especially the neglected endemic diseases such as tuberculosis and
      malaria, is based on the use of defined molecular targets. Among the advantages,
      this approach allows (i) the search and identification of lead compounds with
      defined molecular mechanisms against a defined target (e.g. enzymes from defined
      pathways), (ii) the analysis of a great number of compounds with a favorable
      cost/benefit ratio, (iii) the development even in the initial stages of compounds
      with selective toxicity (the fundamental principle of chemotherapy), (iv) the
      evaluation of plant extracts as well as of pure substances. The current use of
      such technology, unfortunately, is concentrated in developed countries,
      especially in the big pharma. This fact contributes in a significant way to
      hamper the development of innovative new compounds to treat neglected diseases.
      The large biodiversity within the territory of Brazil puts the country in a
      strategic position to develop the rational and sustained exploration of new
      metabolites of therapeutic value. The extension of the country covers a wide
      range of climates, soil types, and altitudes, providing a unique set of selective
      pressures for the adaptation of plant life in these scenarios. Chemical diversity
      is also driven by these forces, in an attempt to best fit the plant communities
      to the particular abiotic stresses, fauna, and microbes that co-exist with them.
      Certain areas of vegetation (Amazonian Forest, Atlantic Forest, Araucaria Forest,
      Cerrado-Brazilian Savanna, and Caatinga) are rich in species and types of
      environments to be used to search for natural compounds active against
      tuberculosis, malaria, and chronic-degenerative diseases. The present review
      describes some strategies to search for natural compounds, whose choice can be
      based on ethnobotanical and chemotaxonomical studies, and screen for their
      ability to bind to immobilized drug targets and to inhibit their activities.
      Molecular cloning, gene knockout, protein expression and purification, N-terminal
      sequencing, and mass spectrometry are the methods of choice to provide
      homogeneous drug targets for immobilization by optimized chemical reactions.
      Plant extract preparations, fractionation of promising plant extracts,
      propagation protocols and definition of in planta studies to maximize product
      yield of plant species producing active compounds have to be performed to provide
      a continuing supply of bioactive materials. Chemical characterization of natural
      compounds, determination of mode of action by kinetics and other spectroscopic
      methods (MS, X-ray, NMR), as well as in vitro and in vivo biological assays,
      chemical derivatization, and structure-activity relationships have to be carried
      out to provide a thorough knowledge on which to base the search for natural
      compounds or their derivatives with biological activity.

PMID- 16302059
TI  - A survey on Triatoma dimidiata in an urban area of the province of Heredia, Costa
      Rica.
AB  - Triatoma dimidiata has been found in several cities and towns of those countries
      where the insect is a domestic or peridomestic pest. In Central America, urban
      infestations occur in the capitals of at least five countries. During 2001 and
      2002 a survey was carried out in the county of San Rafael, Heredia province,
      located 15 km northwest of San Jose, capital of Costa Rica, in order to determine
      the degree of infestation by T. dimidiata in an entire city block. Six
      peridomestic colonies of the insect were detected in the backyards of eight
      households. The ecotopes occupied by the insects consisted of store rooms with
      old objects, wood piles or firewood, and chicken coops. A total of 1917 insects
      were found in the six foci, during two sampling periods, and a mean infection
      rate by Trypanosoma cruzi of 28.4% was found in 1718 insects examined. The
      largest colony found in one of the households yielded 872 insects that were
      thriving mainly at the expenses of two dogs. Opossums and adult insects were
      common visitors of the houses and it became evident that this marsupial is
      closely related to the peridomestic cycle of the Chagas disease agent. Lack of
      colonization of the insect inside the human dwellings is explained by the type of
      construction and good sanitary conditions of the houses, in contrast to the
      situation in most peridomiciliary areas. Stomach blood samples from the insects
      showed that the main hosts were, in order of decreasing frequency: rodents, dogs,
      fowl, humans, opossums, and cats. The fact that no indication of infection with
      Chagas disease could be detected in the human occupants of the infested houses,
      vis a vis the high infection rate in dogs, is discussed.

PMID- 16302060
TI  - Serological survey of Babesia bovis, Babesia bigemina, and Anaplasma marginale
      antibodies in cattle from the semi-arid region of the state of Bahia, Brazil, by
      enzyme-linked immunosorbent assays.
AB  - The objectives of this work were to determine the prevalence of Babesia bovis,
      Babesia bigemina, and Anaplasma marginale detecting antibodies in cattle raised
      in the semi-arid region of the state of Bahia, Brazil, through indirect enzyme
      linked immunosorbent assays (ELISA) and to compare the performances of indirect
      enzyme-linked immunosorbent assays with crude (I-ELISA-CrAnaAg) and recombinant
      major surface protein-5 (I-ELISA-MSP-5Ag), as antigens to detect antibodies
      against A. marginale. An stable enzootic area was found in Senhor do Bonfim and
      Euclides da Cunha for B. bovis that showed 86 and 95.5% of prevalence,
      respectively, and for B. bigemina with 90.8 and 91.3%. On the other hand, Uaua
      and Juazeiro, were characterized as enzootically unstable areas, since
      prevalences were: B. bovis--63.7 and 56.4% and B. bigemina--53 and 54.8%,
      respectively. The prevalence of A. marginale in the four municipalities was above
      97% with I-ELISA-CrAnaAg and 94.8% with I-ELISA-MSP-5Ag which is an indication of
      stable enzootic condition for the rickettsia. The I-ELISA-CrAnaAg and I-ELISA-MSP
      5Ag showed a highly significant association (r = 0.977), which means that both
      ELISA tests are suitable for epidemiological studies of A. marginale.

PMID- 16302061
TI  - Experimental infection of Leishmania (L.) chagasi in a cell line derived from
      Lutzomyia longipalpis (Diptera:Psychodidae).
AB  - The present work describes the in vitro infection of a cell line Lulo, derived
      from Lutzomyia longipalpis embryonic tissue, by Leishmania chagasi promastigotes.
      This infection process is compared with a parallel one developed using the J774
      cell line. The L. chagasi MH/CO/84/CI-044B strain was used for experimental
      infection in two cell lines. The cells were seeded on glass coverslips in 24-well
      plates to reach a final number of 2 x 10(5) cells/well. Parasites were added to
      the adhered Lulo and J774 cells in a 10:1 ratio and were incubated at 28 and 37
      masculineC respectively. After 2, 4, 6, 8, and 10 days post-infection, the cells
      were extensively washed with PBS, fixed with methanol, and stained with Giemsa.
      The number of internalized parasites was determined by counting at least 400
      cultured cells on each coverslip. The results showed continuous interaction
      between L. chagasi promastigotes with the cell lines. Some ultrastructural
      characteristics of the amastigote forms were observed using transmission electron
      microscopy. The highest percentage of infection in Lulo cells was registered on
      day 6 post-infection (29.6%) and on day 4 in the J774 cells (51%). This work
      shows similarities and differences in the L. chagasi experimental infection
      process in the two cell lines. However, Lulo cells emerge as a new model to study
      the life-cycle of this parasite.

PMID- 16302062
TI  - Maintenance and breeding of Thrichomys (Trouessart, 1880) (Rodentia: Echimyidae)
      in captivity.
AB  - South American histricognath rodents Thrichomys apereoides laurentius and
      Thrichomys pachyurus are natural hosts of Trypanosoma cruzi, agent of Chagas
      disease. We established breeding colonies of these species to serve as
      experimental models in various parasitological studies. Both species of
      Thrichomys have all the requirements necessary to become excellent laboratory
      models: they can be easily maintained in the standard laboratory conditions and
      breed throughout the year and they do not have any special dietary demands and
      can be fed by standard food pellets designed for laboratory mice. Both species
      produce precocious offspring that have their eyes and ears open, teeth erupted,
      fur well developed, and can eat solid food in the first week of life. T. a.
      laurentius has larger litter sizes and lower body masses at birth and weaning
      than T. pachyurus. Moreover, females of T. a. laurentius reach puberty earlier
      and with lower body mass than T. pachyurus.

PMID- 16302063
TI  - Variability and genetic differentiation among Anopheles (Ano.) intermedius
      Chagas, 1908 and Anopheles (Ano.) mattogrossensis Lutz & Neiva, 1911 (Diptera:
      Culicidae) from the Brazilian Amazon.
AB  - Anopheles (Anopheles) intermedius and Anopheles (Ano.) mattogrossensis are
      Brazilian anopheline species belonging to the scarcely studied Anopheles
      subgenus. Few studies have been done on the genetic differentiation of these
      species. Both species have been found infected by Plasmodium and are sympatric
      with other anopheline species from the Nyssorhynchus subgenus. Eighteen enzymatic
      loci were analyzed in larval specimens of An. intermedius and An. mattogrossensis
      aiming to estimate the variability and genetic differentiation between these
      species. An. mattogrossensis population showed higher genetic variability (P =
      44.4 and Ho = 0.081 +/- 0.031) than that of An. intermedius (P = 33.3 and Ho =
      0.048 +/- 0.021). Most analyzed loci showed genotypic frequencies according to
      Hardy-Weinberg equilibrium, except for LAP1 and LAP2 in An. intermedius, and EST1
      and PGM loci in An. mattogrossensis. The genetic distance between these species
      (D = 0.683) was consistent with the inter-specific values reported for Anopheles
      subgenus. We verified that the polymorphism and heterozygosity percentile values
      found in both species and compared to those in the literature, showed no relation
      between the level of isozyme variability and geographical distribution. The low
      variability found in these two species is probably more related to the niche they
      occupy than to their geographic distribution.

PMID- 16302064
TI  - Genetic lineages in the yellow fever mosquito Aedes (Stegomyia) aegypti (Diptera:
      Culicidae) from Peru.
AB  - The yellow fever mosquito Aedes aegypti was introduced in Peru in 1852 and was
      considered to be eradicated in 1958. In 2001, Ae. aegypti had been recorded in 15
      out of 24 Peruvian Departments. Peru has great ecological differences between the
      east and west sides of Andes. Because of this, we consider that Ae. aegypti
      populations of both east and west sides can have a genetically distinct
      population structure. In this study we examined genetic variability and
      genealogical relationships among three Ae. aegypti Peruvian populations: Lima,
      Piura (west Andes), and Iquitos (east Andes) using a fragment of the ND4 gene of
      the mitochondrial genome. Three haplotypes were detected among 55 samples. Lima
      and Iquitos showed the same haplotype (Haplotype I), whereas Piura has two
      haplotypes (Haplotype II and III). Haplotype II is four mutational steps apart
      from Haplotype I, while Haplotype III is 13 mutational steps apart from Haplotype
      I in the network. The analysis of molecular variation showed that mostly of the
      detected genetic variation occurs at interpopulational level. The significant
      value Phi(st) suggests that Piura population is structured in relation to Lima
      and Iquitos populations and the gene flow of the ND4 is restricted in Piura when
      compared to Lima and Iquitos. Genetic relationship between haplotype I and
      haplotype II suggests introduction of the same mtDNA lineage into those
      localities. However the existence of a genetically distant haplotype III also
      suggests introduction of at least two Ae. aegypti lineages in Peru.

PMID- 16302065
TI  - Isolation of a fragment homologous to the rp49 constitutive gene of Drosophila in
      the Neotropical malaria vector Anopheles aquasalis (Diptera: Culicidae).
AB  - The constitutive ribosomal gene rp49 is frequently used as an endogenous control
      in Drosophila gene expression experiments. Using the degenerate primer PCR
      technique we have cloned a fragment homologous to this gene in Anopheles
      aquasalis Curry, a Neotropical vector of malaria. In addition, based on this
      first sequence, a new primer was designed, which allowed the isolation of
      fragments of rp49 in two other species, Aedes aegypti (Linnaeus) and Culex
      quinquefasciatus Say, suggesting that it could be used to clone fragments of this
      gene in a number of other mosquito species. Primers were also designed to
      specifically amplify rp49 cDNA fragments in An. aquasalis and Ae. aegypti,
      showing that rp49 could be used as a good constitutive control in gene expression
      studies of these and other vectorially important mosquito species.

PMID- 16302066
TI  - [Comparative morphology of eggs and nymphs of Triatoma vandae Carcavallo,
      Jurberg, Rocha, Galvao, Noireau & Lent, 2002 and Triatoma williami Galvao, Souza
      & Lima, 1965].
AB  - Eggs and all nymphs of these species were studied employing light microscopy (LM)
      and scanning electron microscopy (SEM). The major differences observed by LM in
      the eggs were related to the presence and the distribution of pores on the
      surface of their chorion. Morphological differences among three nymphal stages
      (1st, 3rd, and 5th) development of each species were observed. The differential
      characteristics are chromatic and in the shape of connexival spots. The
      ultrastructure of the ventral region of the head and the IX, X, and XI abdominal
      segments (anal tube) of the both species were described demonstrating
      morphological differences that can be used for diagnosis of the species.

PMID- 16302067
TI  - The neuraminidase gene is present in the non-toxigenic Vibrio cholerae Amazonia
      strain: a different allele in comparison to the pandemic strains.
AB  - The neuraminidase gene, nanH, is present in the O1, non-toxigenic Vibrio cholerae
      Amazonia strain. Its location has been assigned to a 150 kb NotI DNA fragment,
      with the use of pulsed-field gel electrophoresis and DNA hybridization. This NotI
      fragment is positioned inside 630 kb SfiI and 1900 kb I-CeuI fragments of
      chromosome 1. Association of the pathogenicity island VPI-2, carrying nanH and
      other genes, with toxigenic strains has been described by other authors. The
      presence of nanH in a non-toxigenic strain is an exception to this rule. The
      Amazonia strain nanH was sequenced (Genbank accession No. AY825932) and compared
      to available V. cholerae sequences. The sequence is different from those of
      pandemic strains, with 72 nucleotide substitutions. This is the first description
      of an O1 strain with a different nanH allele. The most variable domain of the
      Amazonia NanH is the second lectin wing, comprising 13 out of 17 amino acid
      substitutions. Based on the presence of nanH in the same region of the genome,
      and similarity of the adjacent sequences to VPI-2 sequences, it is proposed that
      the pathogenicity island VPI-2 is present in this strain.

PMID- 16302068
TI  - Antimicrobial susceptibility patterns of unusual nonfermentative gram-negative
      bacilli isolated from Latin America: report from the SENTRY Antimicrobial
      Surveillance Program (1997-2002).
AB  - The antimicrobial susceptibility of 176 unusual non-fermentative gram-negative
      bacilli (NF-GNB) collected from Latin America region through the SENTRY Program
      between 1997 and 2002 was evaluated by broth microdilution according to the
      National Committee for Clinical Laboratory Standards (NCCLS) recommendations.
      Nearly 74% of the NF-BGN belonged to the following genera/species: Burkholderia
      spp. (83), Achromobacter spp. (25), Ralstonia pickettii (16), Alcaligenes spp.
      (12), and Cryseobacterium spp. (12). Generally, trimethoprim/sulfamethoxazole
      (MIC50, < 0.5 microg/ml) was the most potent drug followed by levofloxacin
      (MIC50, 0.5 microg/ml), and gatifloxacin (MIC50, 1 microg/ml). The highest
      susceptibility rates were observed for levofloxacin (78.3%), gatifloxacin
      (75.6%), and meropenem (72.6%). Ceftazidime (MIC50, 4 microg/ml; 83.1%
      susceptible) was the most active beta-lactam against B. cepacia. Against
      Achromobacter spp. isolates, meropenem (MIC50, 0.25 microg/ml; 88% susceptible)
      was more active than imipenem (MIC50, 2 microg/ml). Cefepime (MIC50, 2 microg/ml;
      81.3% susceptible), and imipenem (MIC50, 2 microg/ml; 81.3% susceptible) were
      more active than ceftazidime (MIC50, >16 microg/ml; 18.8% susceptible) and
      meropenem (MIC50, 8 microg/ml; 50% susceptible) against Ralstonia pickettii.
      Since selection of the most appropriate antimicrobial agents for testing and
      reporting has not been established by the NCCLS for many of NF-GNB species,
      results from large multicenter studies may help to guide the best empiric
      therapy.

PMID- 16302069
TI  - Pathology and first report of natural infections of the eye trematode
      Philophthalmus lachrymosus Braun, 1902 (Digenea, Philophthalmidae) in a non-human
      mammalian host.
AB  - The avian eye trematode Philophthalmus lachrymosus Braun, 1902 is for the first
      time referred naturally occurring in a non-human mammalian host. Previously,
      natural infections with P. lachrymosus and other species of Philophthalmus have
      been occasionally reported from man, with few data on experimental infections of
      non-human mammals. Results presented here are related to the report of two cases
      of philophthalmosis due to natural infections of wild Brazilian capybaras,
      Hydrochaeris hydrochaeris L., 1766 with P. lachrymosus and associated pathology.
      Clinical signs, gross and microscopic lesions as well as new morphometric data on
      the parasite are presented.

PMID- 16302070
TI  - The first confirmed case of Diphyllobothrium latum in Brazil.
AB  - Diphyllobothriasis is an infection of the small intestine by the broad tapeworm
      Diphyllobothrium sp. The associated symptomatology is nonspecific, but
      megaloblastic anemia is a well-described complication. Although the infection is
      common in temperate regions, descriptions in South America have so far been
      limited to Chile, Peru, and a few cases in Argentina. This paper presents the
      first confirmed Brazilian case of diphyllobothriasis. A 29-years-old woman living
      in Salvador (state of Bahia) apparently acquired the infection from eating sushi.
      The diagnosis was based on fecal examination that revealed a large quantity of
      operculated eggs. A single dose of praziquantel (600 mg) was sufficient to cure
      the infection.

PMID- 16302071
TI  - Leishmania (Viannia) lainsoni (Kinetoplastida: Trypanosomatidae), a divergent
      Leishmania of the Viannia subgenus--a mini review.
AB  - Leishmania (Viannia) lainsoni is the Leishmania species that presents the most
      distinct biological (morphology, growth in axenic culture medium), biochemical
      (enzymatic electrophoresis profile), and molecular biology characteristics, when
      compared to other species of the Viannia subgenus. Development of promastigote
      forms of this parasite attached to the wall of the pyloric and hind gut regions
      of sand fly vectors is a solid characteristic that allows its positioning in the
      Viannia subgenus. However, taxonomic data from biochemical and molecular
      techniques on this Leishmania species are still not conclusive. It is evident the
      difficulty in taxonomically positioning this borderline Leishmania species. In
      this review we present the data accumulated since L. (Viannia) lainsoni has been
      described and we discuss its position in the Viannia subgenus.

PMID- 16302073
TI  - [Reflections on perspectives on post-graduate education].

PMID- 16302074
TI  - Hypertonic saline and hemorrhagic shock: hepatocellular function and integrity
      after six hours of treatment.
AB  - PURPOSE: The comparison after 6 h of hemorrhagic shock (HS) treatment with NaCl
      7.5% (Hypertonic Saline Solution-SSH) or Ringer Lactate (RL) on liver function
      and integrity. METHODS: Male Wistar rats were submitted to HS (Mean Arterial
      Pressure-MAP= 45 mmHg) during 60 min and then treated with NaCl 7.5% (SSH, 10% of
      blood loss, n=8) or Ringer Lactate (RL, 400% of blood loss, n=8). After 6 h rats
      were anesthetized, hepatic function was assessed by bile flow measurement and
      liver integrity evaluated by determination of alanine aminotransferase (ALT) and
      bilirubin activities. RESULTS: There was no difference in MAP between the groups
      during the whole experiments. Biliary flow showed a significant recovery after
      SSH treatment (p<0.05), and significant decrease of ALT (p<0.001) and bilirubin
      levels (p<0.001) in comparison to RL. CONCLUSION: Resuscitation of HS with NaCl
      7.5% promoted better recovery of liver function and lesser hepatocellular damage
      after 6 h of treatment compared to RL. The improvement is very likely related to
      increased microvascular perfusion provided by small volume resuscitation.

PMID- 16302075
TI  - A new experimental model to study preneoplastic lesions in achalasia of the
      esophagus.
AB  - PURPOSE: Develop an experimental model to study esophageal preneoplastic lesions
      induced by diethylnitrosamine in rats with achalasia. METHODS: Male Wistar rats
      were divided into four groups: control--C (n=8); rats with megaesophagus--B
      (n=8); rats treated with DEN--D (n=15) and rats with megaesophagus plus DEN--BD
      (n=15). Megaesophagus can be experimentally obtained in rats by topical
      application of benzalkonium chloride. The morphology and PCNA labeling index of
      the epithelium were evaluated. RESULTS: The morphometric analysis showed an
      increase in epithelial thickness in the animals of group BD (2166+/-1012 mm2)
      when compared to the other groups (C = 878+/-278 mm2; B = 1746+/-144 mm2 and D =
      1691+/-697 mm2), mainly due to basal layer hyperplasia, besides an increase in
      the keratin of the superficial layer. The PCNA labeling index in the basal layer
      was significantly higher in the group BD (0.695+/-0.111) when compared to the
      other groups (C = 0.490+/-0.132; B = 0.512+/-0.215 and D = 0.477+/-0.198).
      CONCLUSIONS: Our data confirm in an experimental model the previous observation
      in humans of increased epithelial cell proliferation during the esophageal
      carcinogenic process in achalasia and may be useful to further studies on the
      mechanisms of the esophageal carcinogenesis and the the design of follow-up
      endoscopic studies for patients with achalasia.

PMID- 16302076
TI  - Assessment of staging, prognosis and mortality of colorectal cancer by tumor
      markers: receptor erbB-2 and cadherins.
AB  - PURPOSE: To evaluate the prognostic significance and correlation with staging and
      degree of cell differentiation of the tumoral expression of the proteins c-erbB-2
      and E-cadherin, in patients with colorectal adenocarcinoma. METHODS: The study
      included 117 patients with an average age of 63.1 years and an average follow-up
      duration of 28.1 months. The disease-free interval, survival, incidence of
      recurrence and specific mortality were evaluated. c-erbB-2 anti-oncoprotein
      antibodies (Dako) were utilized via the streptavidin-biotin technique. Samples
      were considered to be positive for c-erbB-2 if 10% or more of the tumor cell
      membranes were stained. The anti-E-cadherin antibodies (Dako), evaluated this
      protein and is considered positive, if 50% or more of the cell membranes were
      stained. Statistical analysis was performed using Pearson's chi-squared test,
      Fisher's exact test, Kaplan-Meier's estimator, the log-rank test and Wilcoxon's
      test (Breslow version), setting the level of statistical significance at 5%
      (p<0.05). RESULTS: 52 of 108 patients studied for c-erbB-2 were positive (48.1%),
      47 of 93 patients studied for E-cadherin were negative (50.5%). These data do not
      express any correlation with TNM (tumor, node and metastasis) staging and the
      degree of cell differentiation or with the tumor recurrence rate. The disease
      free interval among patients who were positive for c-erbB-2 and negative for E
      cadherin was 68.0 months and did not differ from those with c-erbB-2 negative and
      E-cadherin positive (55.0 months--p = 0.5510). The average survival among
      patients positive for c-erbB-2 and negative for E-cadherin was 75 months without
      statistical significance difference with the other group (61 months--p = 0.5256).
      Specific mortality occurred in 20.0% of the cases and did not correlate with the
      expression of c-erbB-2 (p=0.446), E-cadherin (p=0.883). CONCLUSION: The tumoral
      expression of c-erbB-2 and E-cadherin did not demonstrate a correlation with the
      staging and degree of cell differentiation, and it did not present prognostic
      value regarding disease recurrence, disease-free interval, survival and specific
      mortality among patients with colorectal adenocarcinoma.

PMID- 16302077
TI  - Effects of different temperatures and periods of preservation in menisci
      cellularity in rabbits.
AB  - PURPOSE: Quantify the progressive decrease of the cellular viability of rabbit
      meniscus preserved for transplants over a 30 day period at different freezing
      temperatures. METHODS: 180 menisci were removed from 45 rabbits. Menisci were
      frozen from 2 to 30 days at -7.2 degrees Celsius -21.4 degrees Celsius and -73
      degrees Celsius. Four menisci from each temperature were thawed every two days
      and the number of present cells was quantified. RESULTS: On the 14th freezing day
      at -7.2 degrees Celsius, there were 92.38% mean viable cells. However, as from
      the 16th day, there has been a significant 12% decrease (p = 0.001), as compared
      to 14th day mean. Mean cell viability at -21.4 degrees Celsius and -73 degrees
      Celsius, until the 16th day was statistically similar. As from the 18th day at 
      21.4 degrees Celsius, there has been significant cell count decrease (p < 0.001),
      especially from the 28th (54.5%) to the 30th (30%) freezing day. The number of
      viable cells at -73 degrees Celsius has shown insignificant 2.3% decrease (p =
      1.000) from the 28th (40.2%) to the 30th (37.9%) day. CONCLUSION: The amount of
      viable meniscus cells is similar up to the 14th day of preservation, under any of
      the used temperatures. However, from the 14th day to the 30th day, the amount of
      viable cells is smaller in lower temperatures.

PMID- 16302078
TI  - Oxidized tissue proteins after intestinal reperfusion injury in rats.
AB  - PURPOSE: To analyse if the carbonyl proteins measurement could be validated as a
      method that allows the identification of an intestinal oxidative stress after
      ischemia and reperfusion injury. METHODS: Twenty-five male Wistar rats (n = 21)
      weighting 200 to 250 g were divided into three groups. Group I--control (n = 10).
      Group II--sham (n = 5) and Group III (n = 10) subjected to 60 minutes of
      intestinal ischemia and equal period of reperfusion. For this purpose it was
      clamped the superior mesenteric artery in its distal third. Histological changes
      and carbonyl protein levels were determined in the samples of all groups. In
      group III, samples of both normal and reperfused ileal segment were studied.
      RESULTS: All the reperfused segments showed mucosal and submucosal swelling and
      inflammatory infiltrate of the lamina propria. Levels of carbonyl protein rose in
      group III, including in the non-ischemic segments. The sensitivity and
      specificity of the carbonyl protein tissue levels were respectively 94% and 88%.
      CONCLUSION: The carbonyl protein method is a useful biologic marker of oxidative
      stress after the phenomenon of intestinal ischemia and reperfusion in rats. It
      was also noteworthy that the effects of oxidative stress could be seen far from
      the locus of the primary injury.

PMID- 16302079
TI  - Experimental model of gastroesophageal reflux in rats.
AB  - PURPOSE: To develop an experimental model of gastroesophageal reflux in rats.
      METHODS: Sixty Wistar rats underwent surgery and were assigned to one of the
      three groups of twenty animals each. The animals in group A underwent total
      esophageal myectomy and, in group (B), underwent partial myectomy. The third
      group was the control group (C). A contrast radiographic study of the esophagus
      was performed to evaluate gastroesophageal reflux. The anatomopathological study
      of the esophagus was used to evaluate esophagitis. RESULTS: During the 30-day
      postoperative follow-up, 14 animals in group A presented with reflux of barium in
      the esophagus. The presence of barium in the esophagus was observed in 7 animals
      in group B and in 2 animals in the control group. The result of the
      histopathology examination was controversial. A marked weight loss in the rats
      undergoing total myectomy was observed, however there was no significant
      statistical difference. CONCLUSION: Total myectomy in the lower third of the
      esophagus caused gastroesophageal reflux in the majority of the animals.

PMID- 16302080
TI  - Effects of L-alanyl-glutamine upon the blood and kidney biochemical parameters in
      the rat hind limb model of ischemia/reperfusion.
AB  - PURPOSE: To investigate the effects of l-alanyl-glutamine (Ala-Gln) intragastric
      administration upon blood and kidney metabolic parameters alterations in rats
      subjected to ischemia/reperfusion of hind limb. METHODS: Forty-eight male rats
      were randomized in 2 groups offered via gavage either saline 2.0 mL (G-1) or Ala
      Gln solution 0.75 mgKg-1(G-2) once a day at 7 AM during 7 days. One-hour after
      the last gavage (Day 7) all rats were submitted to ether anesthesia, laparotomy
      and clamping of the left iliac artery for 3 h. Kidney and blood samples were
      collected at the end of ischemic period (3 h) and at 1-3-6 h during reperfusion
      period for metabolites (pyruvate, lactate, glucose and ketone bodies) enzymatic
      analysis. ATP was also assayed in kidney samples. RESULTS: Lactacemia and
      ketonemia were significantly increased in Ala-Gln treated rats during
      reperfusion. Kidney pyruvate concentrations were significantly decreased and
      tissue lactate concentrations were significantly increased during reperfusion (1
      h and 3 h) in G-2 rats compared with respective controls. Glucose, ATP and ketone
      bodies concentrations were significantly increased in the kidney in L-Ala-Gln
      treated rats at 3 hours after reperfusion as compared to respective controls.
      CONCLUSIONS: Unilateral hind limb ischemia in L-Ala-Gln pre-treated rats may
      induce increased lactacemia and increased kidney lactate concentrations,
      indicating increased glycolytic activity in renal medulla and in other peripheral
      tissues. Higher ketonemia during reperfusion may reflect a possible increase in
      ketogenesis due to lower insulin plasma concentration hepatic signaling as a
      result of increased glucose oxidation in peripheral tissues, caused by the intra
      gastric administration of glutamine dipeptide, suggesting also decreased insulin
      resistance.

PMID- 16302081
TI  - Influence of minoxidil on ischemic cutaneous flaps in rats.
AB  - PURPOSE: To evaluate the influence of minoxidil, a well known vasodilator, on
      ischemic flap necrosis prevention in rats. METHODS: Ventral cutaneous flaps,
      measuring 8x4 cm, were designed in 20 Wistar rats based on the right cranial
      epigastric artery. In the experiment group, 50 mg/kg/day of minoxidil sulfate was
      administered by orogastric tube and the same amount of saline solution was
      administered to the control group. Such procedure was initiated 24 h before
      surgery and kept once a day through the 7th postoperative day. Microcirculation
      was evaluated with laser fluxometry 24 h before surgical procedure, at immediate
      postoperative and at the 7th postoperative day. Flap necrosis area was evaluated
      by 2 methods: planimetry and weight/paper ratio. RESULTS: A significant flow
      increase in distal and medial extremity at M1 (medial point 1) (p=0.0484) was
      observed in the experiment group. There was significant difference in flap
      necrosis prevention in the experiment group (p=0.0433), although after necrosis
      took place there was no significant difference in necrosis size. (p=0.1051 and
      p=0.2799). CONCLUSION: Minoxidil sulfate is effective in avoiding necrosis in
      ischemic flaps, but after necrosis is present there is no difference in survival
      area between experimental and control groups.

PMID- 16302082
TI  - Hypertonic glucose solution 10%-25% on the mesenterium and peritoneum of the rat:
      macroscopic and microscopic study.
AB  - PURPOSE: The objective of the experimental study is to detect the macroscopic and
      microscopic alterations of the mesenterium and parietal peritoneum when
      hypertonic glucose aqueous solution 10%-25% is administrated into the peritoneal
      cavity of the rat. METHODS: 90 Wistar females young rats adults were used
      weighing between 180-250 g, numbered 1 to 90, establishing unique group and
      divided in three groups (A, B, C) of 30 animals chosen aleatory manner. 0.9%
      saline solution was used called control group, or group A, 10% glucose solution
      named group B, and in the others 30 was used 25% glucose solution named group C,
      differing in the observation period, (06 h, 24 h and 48 h), but with the same
      procedure. A midline abdominal wall laparotomy was made and in the animals of the
      control group was injected 2 ml of a 0.9% saline solution into the peritoneal
      cavity. After, we made a suture in mass without to include the peritoneum. For
      the others groups (B, C) the rats received 10% glucose solution and 25% glucose
      solution injected into the peritoneal cavity respectively. All groups were kept
      under observation and the results were submitted to statistical analysis by a
      longitudinal and transversal comparative study. RESULTS: A new surgery was done
      in 6 h, 24 h and 48 h, and we observed in macroscopic evaluation, the presence of
      fluid, serous uniform and rosy all over the cavity. Vascular congestion was
      present. We dried out 90 fragments of mesenterium and 90 fragments of parietal
      peritoneum bilateral. In the microscopic study, necrosis was not present. For the
      mesenterium histological study we observed 16 cases (17.8%) unspecific chronic
      inflammation, 30 cases (33.4%) hyperplasc linfonod, 10 cases (11.1%) high
      vascular congestion, 6 cases (6.6%) reaction fibrosis and 28 cases (31.1%) no
      alteration. For the parietal peritoneum histological study we observed 6 cases
      (3.3%) reaction fibrosis and 174 cases (96.7%) no alteration. Giant cell was not
      present. In the statistical analysis statistic there is no significance between
      the groups (p>0.05). CONCLUSION: Hypertonic glucose solution and NaCl 0.9% on the
      mesenterium and parietal peritoneum do not produce tissue necrosis in a rat and
      the inflammation process has the same intensity.

PMID- 16302083
TI  - Effects of the polypropylene mesh implanted through inguinotomy in the spermatic
      funiculus, epididium and testis of dogs.
AB  - PURPOSE: To investigate the effects of polypropylene mesh, implanted by
      inguinotomy, in the spermatic funiculus, epididium and testis of dogs. METHODS:
      Eighteen dogs were considered (12-23 Kg), separated in three groups. Group A
      (n=7): left side (with mesh) versus right side (without mesh); Group B (n=7):
      left side (without mesh) versus right side (with mesh) and Group C (n=4): without
      any surgical manipulation (control group). After being observed for 60 days, the
      animals were subjected to bilateral removal of the spermatic funiculus, epididium
      and testis that were submitted to histological analysis. During the re-operation,
      a macroscopic evaluation was performed. RESULTS: On the mesh side, we noted 100%
      of mesh adherence to the posterior wall of the inguinal canal, as well as the
      adherence of the spermatic funiculus to the mesh. A congestion of the pampiniform
      plexus was noted in three animals. Chronic inflammation reaction and foreign body
      reaction in the spermatic funiculus was observed in 100% of the animals. On the
      side that did not carry a mesh, chronic inflammatory reaction was observed in 71%
      of the animals. All the animals presented chronic inflammatory reaction in the
      deferent duct in the mesh side and in eleven animals in the side without the
      mesh. These alterations were not found in Group C. There was a considerable
      statistical reduction in the average difference of the diameter of the lumen of
      the deferent duct in the mesh side. In the epididium and testis, macro and
      microscopic alterations were not significant, although one animal presented a
      marked reduction of spermatogenesis on the mesh side. CONCLUSION: The
      polypropylene mesh, when in contact with the spermatic funiculus of dogs, causes
      a more intense chronic inflammatory reaction and a significant reduction in the
      diameter of the lumen of the deferent duct.

PMID- 16302084
TI  - [Effect of allopurinol on rat testicles morphology, submitted to ischaemia for
      spermatic cord torsion followed by reperfusion].
AB  - PURPOSE: In this investigation has been studied the effect of the allopurinol on
      the reperfusion injury phenomenon in testicles of rats. METHODS: Eighty adults
      Wistar rats were divided in 4 groups: sham without allopurinol, sham with
      allopurinol, right testicular torsion for one hour without allopurinol and right
      testicular torsion for one hour with allopurinol. Bilateral orchiectomy was
      performed 60 days of the experiment and the testis were processed for optical
      microscopy, and examined to asses the seminiferous ducts and the spermatogenic
      cells. RESULTS: There was significant atrophy and histological damage of the
      right testis. CONCLUSION: Allopurinol did not protected the testis against the
      effects of the reperfusion injury.

PMID- 16302085
TI  - [Rats resistance to fecal peritonitis when subjected to total splenectomy and
      auto-implant of the spleen in the retroperitoneum].
AB  - PURPOSE: This study was developed to evaluated the effects of spleen transplants
      in the protection against abdominal sepsis in young and old Wistar rats. METHODS:
      Fifty-four young and old Wistar rats were utilized (90 and 180 days respectively)
      being distributed in three groups as follows: Sham Group, where the animal were
      submitted to laparotomy with manipulation of only intestine (n=12 young and adult
      animals), Splenectomy Group, in which the animals were subjected to total
      splenectomy (n=20 young and adult animals) and an Auto-implant Group, where the
      animals were subjected to total splenectomy and a third of the spleen was
      implanted in a bag in the retroperitoneum (n=22 young and adult animals). After
      three months the animals were subjected to a new laparotomy with binding and
      caecum perforation to stimulate abdominal sepsis and were accompanied until the
      moment of death to establish a mortality curve. RESULTS: There was recuperation
      of the spleen implanted in all animals. There was no significant difference in
      the time of death among the groups. The young animals apparently had a better
      response, however it was not statistically significant. CONCLUSION: This study
      demonstrated that spleen implant in the retroperitoneum do not prove to be an
      effective protection against abdominal sepsis in comparison with the
      splenectomized rats.

PMID- 16302086
TI  - Laser for the treatment of twin to twin transfusion syndrome.
AB  - PURPOSE: To report the initial experience in our country with a new technique for
      twin to twin transfusion syndrome (TTTS) treatment, using laser to coagulate the
      placental vessels responsible for the twin transfusion during gestation. METHODS:
      Prospective study of eight cases diagnosed with TTTS evaluated in our service
      from january 2001 to june 2005. Through percutaneous introduction of a 2,0mm
      diameter fetoscope in the uterine cavity, placental surface vessels where
      directly visualized. Those identified as responsible for the transfusion were
      laser coagulated. The procedure combines ultrasonography and fetoscopy, in a so
      called sonoendoscopic technique (FETENDO). RESULTS: Among the eight pregnancies
      evaluated, five cases were submitted to the procedure (10 fetuses). All fetuses
      survived for at least five weeks after surgery. A total of eight fetuses were
      born alive and five survived the neonatal period. In a 18 months follow-up after
      birth, all five are still alive and well and their mean age is now 10,6 months.
      The total survival rate was 50% and in three pregnancies, at least one fetus
      survived. CONCLUSIONS: Laser fetoscopy is actually the "gold-standard" treatment
      of TTTS. Nevertheless is a sophisticated technique that depends of proper
      training. Our service is the first in our country to offer this therapeutic
      technique. Our success rate is comparable with the international literature.

PMID- 16302087
TI  - Hepatitis C virus infection, cryoglobulinemia, and peripheral neuropathy: a case
      report.
AB  - Hepatitis C virus (HCV) is essentially hepatotropic but its manifestations can
      extend beyond the liver. It can be associated with autoimmune diseases, such as
      mixed cryoglobulinemia, membranoproliferative glomerulonephritis, autoimmune
      thyroiditis, and lymphoproliferative disorders. The mechanisms that trigger these
      manifestations are not completely understood. We describe a 48-year-old man with
      chronic HCV infection (circulating HCV RNA and moderate hepatitis as indicated by
      liver biopsy), cryoglobulinemia, and sensory and motor peripheral neuropathy. The
      diagnosis of multineuropathy was confirmed by clinical examination and
      electromyographic tests. A nerve biopsy revealed an inflammatory infiltrate in
      the perineurial space and signs of demyelination and axonal degeneration. The
      patient had no improvement of neurological symptoms with the use of analgesics
      and neuro-modulators. He was then treated with interferon-alpha (3 million units
      subcutaneously, 3 times per week) and ribavirin (500 mg orally, twice a day) for
      48 weeks. Six months after the end of therapy, the patient had sustained viral
      response (negative HCV RNA) and remission of neurological symptoms, but
      cryoglobulins remained positive. A review of the literature on the pathogenesis
      and treatment of neurological manifestations associated with HCV infection is
      presented. This report underscores the need for a thorough evaluation of HCV
      infected patients because of the possibility of extrahepatic manifestations.
      Antiviral treatment with interferon and ribavirin can be effective and should be
      considered in patients with neurological complications associated with HCV
      infection.

PMID- 16302088
TI  - Protein-mediated surface structuring in biomembranes.
AB  - The lipids and proteins of biomembranes exhibit highly dissimilar conformations,
      geometrical shapes, amphipathicity, and thermodynamic properties which constrain
      their two-dimensional molecular packing, electrostatics, and interaction
      preferences. This causes inevitable development of large local tensions that
      frequently relax into phase or compositional immiscibility along lateral and
      transverse planes of the membrane. On the other hand, these effects constitute
      the very codes that mediate molecular and structural changes determining and
      controlling the possibilities for enzymatic activity, apposition and
      recombination in biomembranes. The presence of proteins constitutes a major
      perturbing factor for the membrane sculpturing both in terms of its surface
      topography and dynamics. We will focus on some results from our group within this
      context and summarize some recent evidence for the active involvement of
      extrinsic (myelin basic protein), integral (Folch-Lees proteolipid protein) and
      amphitropic (c-Fos and c-Jun) proteins, as well as a membrane-active amphitropic
      phosphohydrolytic enzyme (neutral sphingomyelinase), in the process of lateral
      segregation and dynamics of phase domains, sculpturing of the surface topography,
      and the bi-directional modulation of the membrane biochemical reactivity.

PMID- 16302089
TI  - The RNA interference revolution.
AB  - The discovery of double-stranded RNA-mediated gene silencing has rapidly led to
      its use as a method of choice for blocking a gene, and has turned it into one of
      the most discussed topics in cell biology. Although still in its infancy, the
      field of RNA interference has already produced a vast array of results, mainly in
      Caenorhabditis elegans, but recently also in mammalian systems. Micro-RNAs are
      short hairpins of RNA capable of blocking translation, which are transcribed from
      genomic DNA and are implicated in several aspects from development to cell
      signaling. The present review discusses the main methods used for gene silencing
      in cell culture and animal models, including the selection of target sequences,
      delivery methods and strategies for a successful silencing. Expected developments
      are briefly discussed, ranging from reverse genetics to therapeutics. Thus, the
      development of the new paradigm of RNA-mediated gene silencing has produced two
      important advances: knowledge of a basic cellular mechanism present in the
      majority of eukaryotic cells and access to a potent and specific new method for
      gene silencing.

PMID- 16302090
TI  - Prostanoids modulate inflammation and alloimmune responses during graft
      rejection.
AB  - Acute rejection of a transplanted organ is characterized by intense inflammation
      within the graft. Yet, for many years transplant researchers have overlooked the
      role of classic mediators of inflammation such as prostaglandins and thromboxane
      (prostanoids) in alloimmune responses. It has been demonstrated that local
      production of prostanoids within the allograft is increased during an episode of
      acute rejection and that these molecules are able to interfere with graft
      function by modulating vascular tone, capillary permeability, and platelet
      aggregation. Experimental data also suggest that prostanoids may participate in
      alloimmune responses by directly modulating T lymphocyte and antigen-presenting
      cell function. In the present paper, we provide a brief overview of the
      alloimmune response, of prostanoid biology, and discuss the available evidence
      for the role of prostaglandin E2 and thromboxane A2 in graft rejection.

PMID- 16302091
TI  - Differential activity of a lectin from Solieria filiformis against human
      pathogenic bacteria.
AB  - A lectin isolated from the red alga Solieria filiformis was evaluated for its
      effect on the growth of 8 gram-negative and 3 gram-positive bacteria cultivated
      in liquid medium (three independent experiments/bacterium). The lectin (500
      microg/mL) stimulated the growth of the gram-positive species Bacillus cereus and
      inhibited the growth of the gram-negative species Serratia marcescens, Salmonella
      typhi, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus sp, and Pseudomonas
      aeruginosa at 1000 microg/mL but the lectin (10-1000 microg/mL) had no effect on
      the growth of the gram-positive bacteria Staphylococcus aureus and B. subtilis,
      or on the gram-negative bacteria Escherichia coli and Salmonella typhimurium. The
      purified lectin significantly reduced the cell density of gram-negative bacteria,
      although no changes in growth phases (log, exponential and of decline) were
      observed. It is possible that the interaction of S. filiformis lectin with the
      cell surface receptors of gram-negative bacteria promotes alterations in the flow
      of nutrients, which would explain the bacteriostatic effect. Growth stimulation
      of the gram-positive bacterium B. cereus was more marked in the presence of the
      lectin at a concentration of 1000 microg/mL. The stimulation of the growth of B.
      cereus was not observed when the lectin was previously incubated with mannan (125
      microg/mL), its hapten. Thus, we suggest the involvement of the binding site of
      the lectin in this effect. The present study reports the first data on the
      inhibition and stimulation of pathogenic bacterial cells by marine alga lectins.

PMID- 16302092
TI  - Immunophenotype of hematopoietic stem cells from placental/umbilical cord blood
      after culture.
AB  - Identification and enumeration of human hematopoietic stem cells remain
      problematic, since in vitro and in vivo stem cell assays have different outcomes.
      We determined if the altered expression of adhesion molecules during stem cell
      expansion could be a reason for the discrepancy. CD34+CD38- and CD34+CD38+ cells
      from umbilical cord blood were analyzed before and after culture with
      thrombopoietin (TPO), FLT-3 ligand (FL) and kit ligand (KL; or stem cell factor)
      in different combinations: TPO + FL + KL, TPO + FL and TPO, at concentrations of
      50 ng/mL each. Cells were immunophenotyped by four-color fluorescence using
      antibodies against CD11c, CD31, CD49e, CD61, CD62L, CD117, and HLA-DR. Low
      density cord blood contained 1.4 +/- 0.9% CD34+ cells, 2.6 +/- 2.1% of which were
      CD38-negative. CD34+ cells were isolated using immuno-magnetic beads and cultured
      for up to 7 days. The TPO + FL + KL combination presented the best condition for
      maintenance of stem cells. The total cell number increased 4.3 +/- 1.8-fold, but
      the number of viable CD34+ cells decreased by 46 +/- 25%. On the other hand, the
      fraction of CD34+CD38- cells became 52.0 +/- 29% of all CD34+ cells. The absolute
      number of CD34+CD38- cells was expanded on average 15 +/- 12-fold when CD34+
      cells were cultured with TPO + FL + KL for 7 days. The expression of CD62L, HLA
      DR and CD117 was modulated after culture, particularly with TPO + FL + KL,
      explaining differences between the adhesion and engraftment of primary and
      cultured candidate stem cells. We conclude that culture of CD34+ cells with TPO +
      FL + KL results in a significant increase in the number of candidate stem cells
      with the CD34+CD38- phenotype.

PMID- 16302094
TI  - Effect of salbutamol on innervated and denervated rat soleus muscle.
AB  - The objective of the present investigation was to perform a 14-day time-course
      study of treatment with salbutamol, a beta2 adrenoceptor agonist, on rat soleus
      muscle in order to assess fiber type selectivity in the hypertrophic response and
      fiber type composition. Male Wistar rats were divided into four groups: control
      (N = 10), treated with salbutamol (N = 30), denervated (N = 30), and treated with
      salbutamol after denervation (N = 30). Salbutamol was injected intraperitoneally
      in the rats of the 2nd and 4th groups at a concentration of 0.3 mg/kg twice a day
      for 2 weeks. The muscles were denervated using the crush method with pean. The
      animals were sacrificed 3, 6, 9, 12, and 14 days after treatment. Frozen cross
      sections of soleus muscle were stained for myosin ATPase, pH 9.4. Cross-sectional
      area and percent of muscle fibers were analyzed morphometrically by computerized
      image analysis. Treatment with salbutamol induced hypertrophy of all fiber types
      and a higher percentage of type II fibers (21%) in the healthy rat soleus muscle.
      Denervation caused marked atrophy of all fibers and conversion from type I to
      type II muscle fibers. Denervated muscles treated with salbutamol showed a
      significantly larger cross-sectional area of type I muscle fibers, 28.2% compared
      to the denervated untreated muscle. Moreover, the number of type I fibers was
      increased. These results indicate that administration of salbutamol is able to
      induce changes in cross-sectional area and fiber type distribution in the early
      phase of treatment. Since denervation-induced atrophy and conversion from type I
      to type II fibers were improved by salbutamol treatment we propose that
      salbutamol, like other beta2 adrenoceptor agonists, may have a therapeutic
      potential in improving the condition of skeletal muscle after denervation.

PMID- 16302093
TI  - Curcumin induces human HT-29 colon adenocarcinoma cell apoptosis by activating
      p53 and regulating apoptosis-related protein expression.
AB  - Curcumin, a major yellow pigment and active component of turmeric, has multiple
      anti-cancer properties. However, its molecular targets and mechanisms of action
      on human colon adenocarcinoma cells are unknown. In the present study, we
      examined the effects of curcumin on the proliferation of human colon
      adenocarcinoma HT-29 cells by the 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide method and confirmed the curcumin-induced apoptosis
      by morphology and DNA ladder formation. At the same time, p53, phospho-p53
      (Ser15), and other apoptosis-related proteins such as Bax, Bcl-2, Bcl-xL, pro
      caspase-3, and pro-caspase-9 were determined by Western blot analysis. The colon
      adenocarcinoma cells were treated with curcumin (0-75 microM) for 0-24 h. We
      observed that p53 was highly expressed in HT-29 cells and curcumin could up
      regulate the serine phosphorylation of p53 in a time- and concentration-dependent
      manner. An increase in expression of the pro-apoptotic factor Bax and a decrease
      in expression of the anti-apoptotic factor Bcl-2 were also observed in a time
      dependent manner after exposure of 50 microM curcumin, while the expression of
      the anti-apoptotic factor Bcl-xL was unchanged. Curcumin could also down-regulate
      the expression of pro-caspase-3 and pro-caspase-9 in a time-dependent manner.
      These data suggest a possible underlying molecular mechanism whereby curcumin
      could induce the apoptosis signaling pathway in human HT-29 colon adenocarcinoma
      cells by p53 activation and by the regulation of apoptosis-related proteins. This
      property of curcumin suggests that it could have a possible therapeutic potential
      in colon adenocarcinoma patients.

PMID- 16302095
TI  - Genetic potential for an acute inflammatory response in IgA glomerulonephritis in
      mice.
AB  - Mice selected on the basis of an acute inflammatory response (AIR) can provide
      information about the immunopathological mechanisms of glomerulonephritis. We
      studied the differences between mice selected for a maximal AIR (AIRmax that
      attract more polymorphonuclear cells to the site of injury) or a minimal AIR
      (AIRmin that attract more mononuclear cells) in an experimental model of IgA
      nephropathy in order to investigate the effect of genetic background on
      glomerular disease progression and the participation of the monocyte
      chemoattractant protein-1 (MCP-1) chemokine. IgA nephropathy was induced by
      intraperitoneal ovalbumin injection and bile duct ligation in AIRmax and AIRmin
      mice. Histological changes, urinary protein/creatinine ratio, serum IgA levels,
      immunofluorescence for IgA, IgG and complement C3 fraction, immunohistochemistry
      for macrophages and MCP-1, and MCP-1 levels in macerated kidney were determined.
      Mesangial IgA deposition was seen only in AIRmin mice, which presented more renal
      lesions. Increased serum IgA levels (1.5 +/- 0.4 vs 0.3 +/- 0.1 mg/mL, P <
      0.001), high glomerular MCP-1 expression and decreased monocyte/macrophage
      infiltration in the interstitial area (0.3 +/- 0.3 vs 1.1 +/- 0.9
      macrophages/field, P < 0.05) were detected in AIRmin mice compared to AIRmax
      mice. No glomerular monocyte/macrophage infiltration was detected in either
      strain. In spite of the absence of IgA deposition, AIRmax mice presented discrete
      or absent mesangial proliferation. The study showed that there are differences
      between mice selected for AIRmax and AIRmin with respect to serum IgA levels,
      histological damage and MCP-1 chemokine production after ovalbumin injection in
      combination with bile duct ligation.

PMID- 16302096
TI  - Effect of intraperitoneally administered hydrolyzed whey protein on blood
      pressure and renal sodium handling in awake spontaneously hypertensive rats.
AB  - The present study evaluated the acute effect of the intraperitoneal (ip)
      administration of a whey protein hydrolysate (WPH) on systolic arterial blood
      pressure (SBP) and renal sodium handling by conscious spontaneously hypertensive
      rats (SHR). The ip administration of WPH in a volume of 1 ml dose-dependently
      lowered the SBP in SHR 2 h after administration at doses of 0.5 g/kg (0.15 M
      NaCl: 188.5 +/- 9.3 mmHg vs WPH: 176.6 +/- 4.9 mmHg, N = 8, P = 0.001) and 1.0
      g/kg (0.15 M NaCl: 188.5 +/- 9.3 mmHg vs WPH: 163.8 +/- 5.9 mmHg, N = 8, P =
      0.0018). Creatinine clearance decreased significantly (P = 0.0084) in the WPH
      treated group (326 +/- 67 microL min-1 100 g body weight-1) compared to 0.15 M
      NaCl-treated (890 +/- 26 microL min-1 100 g body weight-1) and captopril-treated
      (903 +/- 72 microL min-1 100 g body weight-1) rats. The ip administration of 1.0
      g WPH/kg also decreased fractional sodium excretion to 0.021 +/- 0.019% compared
      to 0.126 +/- 0.041 and 0.66 +/- 0.015% in 0.15 M NaCl and captopril-treated rats,
      respectively (P = 0.033). Similarly, the fractional potassium excretion in WPH
      treated rats (0.25 +/- 0.05%) was significantly lower (P = 0.0063) than in
      control (0.91 +/- 0.15%) and captopril-treated rats (1.24 +/- 0.30%),
      respectively. The present study shows a decreased SBP in SHR after the
      administration of WPH associated with a rise in tubule sodium reabsorption
      despite an angiotensin I-converting enzyme (ACE)-inhibiting in vitro activity
      (IC50 = 0.68 mg/mL). The present findings suggest a pathway involving ACE
      inhibition but measurements of plasma ACE activity and angiotensin II levels are
      needed to support this suggestion.

PMID- 16302097
TI  - Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice.
AB  - Nitric oxide (.NO) is a diffusible messenger implicated in Trypanosoma cruzi
      resistance. Excess production of .NO and oxidants leads to the generation of
      nitrogen dioxide (.NO2), a strong nitrating agent. Tyrosine nitration is a post
      translational modification resulting from the addition of a nitro (-NO2) group to
      the ortho-position of tyrosine residues. Detection of protein 3-nitrotyrosine is
      regarded as a marker of nitro-oxidative stress and is observed in inflammatory
      processes. The formation and role of nitrating species in the control and
      myocardiopathy of T. cruzi infection remain to be studied. We investigated the
      levels of .NO and protein 3-nitrotyrosine in the plasma of C3H and BALB/c mice
      and pharmacologically modulated their production during the acute phase of T.
      cruzi infection. We also looked for protein 3-nitrotyrosine in the hearts of
      infected animals. Our results demonstrated that C3H animals produced higher
      amounts of .NO than BALB/c mice, but their generation of peroxynitrite was not
      proportionally enhanced and they had higher parasitemias. While N G-nitro
      arginine methyl ester treatment abolished .NO production and drastically
      augmented the parasitism, mercaptoethylguanidine and guanido-ethyl disulfide, at
      doses that moderately reduced the .NO and 3-nitrotyrosine levels, paradoxically
      diminished the parasitemia in both strains. Nitrated proteins were also
      demonstrated in myocardial cells of infected mice. These data suggest that the
      control of T. cruzi infection depends not only on the capacity to produce .NO,
      but also on its metabolic fate, including the generation of nitrating species
      that may constitute an important element in parasite resistance and collateral
      myocardial damage.

PMID- 16302099
TI  - Patterns of cerebral activation during lexical and phonological reading in
      Portuguese.
AB  - According to the concepts of cognitive neuropsychology, there are two principal
      routes of reading processing: a lexical route, in which global reading of words
      occurs and a phonological route, responsible for the conversion of the graphemes
      into their respective phonemes. In the present study, functional magnetic
      resonance imaging (fMRI) was used to investigate the patterns of cerebral
      activation in lexical and phonological reading by 13 healthy women with a formal
      educational level greater than 11 years. Participants were submitted to a silent
      reading task containing three types of stimuli: real words (irregular and foreign
      words), nonwords and illegitimate graphic stimuli. An increased number of
      activated voxels were identified by fMRI in the word reading (lexical processing)
      than in the nonword reading (phonological processing) task. In word reading,
      activation was greater than for nonwords in the following areas: superior, middle
      and inferior frontal gyri, and bilateral superior temporal gyrus, right
      cerebellum and the left precentral gyrus, as indicated by fMRI. In the reading of
      nonwords, the activation was predominant in the right cerebellum and in the left
      superior temporal gyrus. The results of the present study suggest the existence
      of differences in the patterns of cerebral activation during lexical and
      phonological reading, with greater involvement of the right hemisphere in reading
      words than nonwords.

PMID- 16302098
TI  - Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2
      virus for rhesus monkeys.
AB  - A chimeric yellow fever (YF)-dengue serotype 2 (dengue 2) virus was constructed
      by replacing the premembrane and envelope genes of the YF 17D virus with those
      from dengue 2 virus strains of Southeast Asian genotype. The virus grew to high
      titers in Vero cells and, after passage 2, was used for immunogenicity and
      attenuation studies in rhesus monkeys. Subcutaneous immunization of naive rhesus
      monkeys with the 17D-D2 chimeric virus induced a neutralizing antibody response
      associated with the protection of 6 of 7 monkeys against viremia by wild-type
      dengue 2 virus. Neutralizing antibody titers to dengue 2 were significantly lower
      in YF-immune animals than in YF-naive monkeys and protection against challenge
      with wild-type dengue 2 virus was observed in only 2 of 11 YF-immune monkeys. An
      anamnestic response to dengue 2, indicated by a sharp increase of neutralizing
      antibody titers, was observed in the majority of the monkeys after challenge with
      wild-type virus. Virus attenuation was demonstrated using the standard monkey
      neurovirulence test. The 17D-D2 chimera caused significantly fewer histological
      lesions than the YF 17DD virus. The attenuated phenotype could also be inferred
      from the limited viremias compared to the YF 17DD vaccine. Overall, these results
      provide further support for the use of chimeric viruses for the development of a
      new live tetravalent dengue vaccine.

PMID- 16302100
TI  - Changes in the biogenic amine content of the prefrontal cortex, amygdala, dorsal
      hippocampus, and nucleus accumbens of rats submitted to single and repeated
      sessions of the elevated plus-maze test.
AB  - It has been demonstrated that exposure to a variety of stressful experiences
      enhances fearful reactions when behavior is tested in current animal models of
      anxiety. Until now, no study has examined the neurochemical changes during the
      test and retest sessions of rats submitted to the elevated plus maze (EPM). The
      present study uses a new approach (HPLC) by looking at the changes in dopamine
      and serotonin levels in the prefrontal cortex, amygdala, dorsal hippocampus, and
      nucleus accumbens in animals upon single or double exposure to the EPM (one-trial
      tolerance). The study involved two experiments: i) saline or midazolam (0.5
      mg/kg) before the first trial, and ii) saline or midazolam before the second
      trial. For the biochemical analysis a control group injected with saline and not
      tested in the EPM was included. Stressful stimuli in the EPM were able to elicit
      one-trial tolerance to midazolam on re-exposure (61.01%). Significant decreases
      in serotonin contents occurred in the prefrontal cortex (38.74%), amygdala
      (78.96%), dorsal hippocampus (70.33%), and nucleus accumbens (73.58%) of the
      animals tested in the EPM (P < 0.05 in all cases in relation to controls not
      exposed to the EPM). A significant decrease in dopamine content was also observed
      in the amygdala (54.74%, P < 0.05). These changes were maintained across trials.
      There was no change in the turnover rates of these monoamines. We suggest that
      exposure to the EPM causes reduced monoaminergic neurotransmission activity in
      limbic structures, which appears to underlie the "one-trial tolerance"
      phenomenon.

PMID- 16302101
TI  - Acute effects of selective serotonin reuptake inhibitors on neuroleptic-induced
      catalepsy in mice.
AB  - Depression found in Parkinson disease (PD) usually responds to selective
      serotonin reuptake inhibitors (SSRIs). Drugs that modify experimental neuroleptic
      catalepsy (NC) might affect extrapyramidal symptoms in PD. Therefore, the effects
      of SSRIs on NC were tested in mice, 26-36 g, separated by sex. Catalepsy was
      induced with haloperidol (H; 1 mg/kg, ip) and measured at 30-min intervals using
      a bar test. An SSRI (sertraline, ST; paroxetine, PX; fluoxetine) or vehicle (C)
      was injected ip 30 min before H. Dunnett's test was used for comparison of means.
      ST (1-5 mg/kg) or PX (1-5 mg/kg) attenuated NC, with a similar inhibition found
      in both sexes (5 mg/kg, 180 min: ST - males: 124 +/- 10 vs 714 +/- 15 s in C;
      females: 116 +/- 10 vs 718 +/- 6 s in C; PX - males: 106 +/- 10 vs 714 +/- 14 s
      in C; females: 102 +/- 10 vs 715 +/- 14 s in C). At 0.3 mg/kg, neither of these
      drugs affected NC. Fluoxetine (1-25 mg/kg) also inhibited catalepsy, although the
      effect was not dose-dependent; no differences were observed between males and
      females (5 mg/kg, 180 min: males, 185 +/- 14 vs 712 +/- 14 s in C; females, 169
      +/- 10 vs 710 +/- 19 s in C). For these SSRIs, maximal inhibition of NC was
      obtained with 5 mg/kg, 180 min after H. These results are consistent with the
      hypothesis that serotonergic mechanisms modulate nigrostriatal transmission, and
      suggest that SSRIs are possibly safe in depressive PD patients.

PMID- 16302102
TI  - Antiprotozoal and molluscicidal activities of five Brazilian plants.
AB  - Leishmaniasis, Chagas' disease and schistosomiasis (bilharzia) are parasitic
      diseases with wide distribution on the American continent, affecting millions of
      people. In the present study, biological assays for antiprotozoal and
      molluscicidal activities were carried out with ethanolic extracts of plant
      species from the Brazilian part of the Upper Parana River. Crude extracts were
      obtained by percolation with absolute ethanol from the leaves of Cayaponia
      podantha Cogn., Nectandra falcifolia (Nees) Castiglioni and Paullinia elegans
      Cambess., as well as from the aerial parts of Helicteres gardneriana St. Hil. &
      Naud. and Melochia arenosa Benth., all belonging to genera used in folk medicine.
      Trypanocidal activity of plants was assayed on epimastigote cultures in liver
      infusion tryptose. Anti-leishmanial activity was determined over cultures of
      promastigote forms of the parasite in Schneider's Drosophila medium. Microscopic
      countings of parasites, after their incubation in the presence of different
      concentrations of the crude extracts, were made in order to determine the
      percentage of growth inhibition. C. podantha and M. arenosa, at a concentration
      of 10 microg/mL, showed 90.4 +/- 11.52 and 88.9 +/- 2.20% growth inhibition,
      respectively, of epimastigote forms of Trypanosoma cruzi, whereas N. falcifolia
      demonstrated an LD50 of 138.5 microg/mL against promastigote forms of Leishmania
      (Viannia) braziliensis. Regarding molluscicidal activity, the acute toxicity of
      the extracts on Biomphalaria glabrata was evaluated by a rapid screening
      procedure. M. arenosa was 100% lethal to snails at 200 microg/mL and showed an
      LD50 of 143 microg/mL. Screening of plant extracts represents a continuous effort
      to find new antiparasitic drugs.

PMID- 16302103
TI  - Pharmacokinetic and parasitological evaluation of the bone marrow of dogs with
      visceral leishmaniasis submitted to multiple dose treatment with liposome
      encapsulated meglumine antimoniate.
AB  - The aim of the present study was to evaluate the impact of a multiple dose
      regimen of a liposomal formulation of meglumine antimoniate (LMA) on the
      pharmacokinetics of antimony in the bone marrow of dogs with visceral
      leishmaniasis and on the ability of LMA to eliminate parasites from this tissue.
      Dogs naturally infected with Leishmania chagasi received 4 intravenous doses of
      either LMA (6.5 mg antimony/kg body weight, N = 9), or empty liposomes (at the
      same lipid dose as LMA, N = 9) at 4-day intervals. A third group of animals was
      untreated (N = 8). Before each administration and at different times after
      treatment, bone marrow was obtained and analyzed for antimony level (LMA group)
      by electrothermal atomic absorption spectrometry, and for the presence of
      Leishmania parasites (all groups). There was a significant increase of antimony
      concentration from 0.76 microg/kg wet organ (4 days after the first dose) to 2.07
      microg/kg (4 days after the fourth dose) and a half-life of 4 days for antimony
      elimination from the bone marrow. Treatment with LMA significantly reduced the
      number of dogs positive for parasites (with at least one amastigote per 1000 host
      cells) compared to controls (positive dogs 30 days after treatment: 0 of 9 in the
      LMA group, 3 of 9 in the group treated with empty liposomes and 3 of 8 in the
      untreated group). However, complete elimination of parasites was not achieved. In
      conclusion, the present study showed that multiple dose treatment with LMA was
      effective in improving antimony levels in the bone marrow of dogs with visceral
      leishmaniasis and in reducing the number of positive animals, even though it was
      not sufficient to achieve complete elimination of parasites.

PMID- 16302104
TI  - Electrocardiographic studies of the three-toed sloth, Bradypus variegatus.
AB  - Electrocardiograms (ECG) obtained with standard limb leads and augmented unipolar
      limb leads were recorded from 17 unanesthetized adult sloths. The animals were
      held in their habitual position in an experimental chair. We determined heart
      rate and rhythm from the R-R intervals, the amplitude and duration of each wave,
      and the duration of the segments and intervals of the ECG. The mean electrical
      axes of P and T waves and QRS complex were calculated on the basis of the
      amplitude of these waves in leads I, II, III, aV R, aV L, and aV F. The P wave
      appeared positive in most tracings with low amplitude in lead II, the QRS complex
      was generally negative in leads aV R, III and aV F, and no arrhythmias were
      observed. With a mean +/- SD heart rate for all recordings of 81 +/- 18 bpm, the
      duration of P and T waves, QRS complex, and PR, QT and RR intervals averaged 0.05
      +/- 0.02, 0.15 +/- 0.05, 0.07 +/- 0.02, 0.13 +/- 0.02, 0.38 +/- 0.04, and 0.74 +/
      0.17 s, respectively. The ECG shape had a definite configuration on each lead.
      The angles of the mean +/- SD electrical axes for atrial and ventricular
      depolarization and ventricular repolarization in the horizontal plane were +34 +/
      68 masculine, -35 +/- 63 masculine, and -23 +/- 68 masculine, respectively. All
      electrical axes showed great variations and their mean values suggest that, when
      the sloth is in a seated position, the heart could be displaced by the diaphragm
      to a semi-horizontal position.

PMID- 16302105
TI  - Socio-demographic and epidemiological characteristics associated with human
      immunodeficiency virus type I (HIV-1) infection in HIV-1-exposed but uninfected
      individuals, and in HIV-1-infected patients from a southern Brazilian population.
AB  - The ability to control human immunodeficiency virus type 1 (HIV-1) infection and
      progression of the disease is regulated by host and viral factors. This cross
      sectional study describes the socio-demographic and epidemiological
      characteristics associated with HIV-1 infection in 1,061 subjects attended in
      Londrina and region, south of Brazil: 136 healthy individuals (Group 1), 147 HIV
      1-exposed but uninfected individuals (Group 2), 161 HIV-1-infected asymptomatic
      patients (Group 3), and 617 patients with AIDS (Group 4). Data were obtained by a
      standardized questionnaire and serological tests. The age of the individuals
      ranged from 15.1 to 79.5 years, 54.0% and 56.1% of the Groups 3 and 4 patients,
      respectively, were men. The major features of groups 2, 3, and 4 were a
      predominance of education level up to secondary school (55.8%, 60.2% and 62.4%,
      respectively), sexual route of exposure (88.4%, 87.0% and 82.0%, respectively),
      heterosexual behavior (91.8%, 75.2% and 83.7%, respectively), and previous
      sexually transmitted diseases (20.4%, 32.5%, and 38.1%, respectively). The
      patients with AIDS showed the highest rates of seropositivity for syphilis
      (25.6%), of anti-HCV (22.3%), and anti-HTLV I/II obtained by two serological
      screening tests (6.2% and 6.8%, respectively). The results documenting the
      predominant characteristics for HIV-1 infection among residents of Londrina and
      region, could be useful for the improvement of current HIV-1 prevention,
      monitoring and therapeutic programs targeted at this population.

PMID- 16302106
TI  - Patients with chronic hepatitis C and normal transaminases.
AB  - Hepatitis C virus infection evolves progressively persisting in the majority of
      patients (85%). Most patients have high ALT (alanine aminotransferase) levels and
      approximately 25% normal ALT. The latter are usually female and there is no
      association between genotype and severity of hepatic lesion. Histologic analysis
      usually shows small lesion and absence or low amount of fibrosis, despite
      cirrhosis having been reported. Aiming at assessing prevalence, demographic,
      genotypical and anatomopathological characteristics in patients with normal ALT
      levels, we have carried out a study of 68 chronic hepatitis C patients between
      January 1997 and April 2000. There was a prevalence of 13.8% chronic hepatitis C
      patients with normal ALT levels, 45.6% of which were male and 54.4% female, the
      mean age being 38 +/- 13 years. We found a predominance of genotype 1 in 84.7% of
      the patients, genotype 2 in 6.8% and genotype 3 in 10.7%. In 52.9% of the cases
      liver biopsies revealed liver reaction, periportal activity score 0-1 was
      observed in 85.3% of the patients and score 2-4 was seen in 14.7%. Structural
      activity score 0-1 was seen in 73.5% of the patients and score 2-4 in 26.5% of
      them. Periportal activity > or = 2 and structural activity > 1 was seen in 29%,
      but steatosis was not seen in 73.5%. Our results suggest the need to revisit for
      liver biopsy practice in patients with chronic hepatitis C and normal
      transaminases.

PMID- 16302107
TI  - Antifungal susceptibilities of clinical and environmental isolates of
      Cryptococcus neoformans in Goiania city, Goias, Brazil.
AB  - We evaluated the antifungal activities of amphotericin B, fluconazole,
      itraconazole and voriconazole in 70 Cryptococcus neoformans strains obtained from
      cerebrospinal fluid from AIDS patients and 40 C. neoformans strains isolated from
      the environment. Four clinical isolates were identified as C. neoformans var.
      gattii. The susceptibility test was done using a broth microdilution method
      according to NCCLS M27-A2. Range minimal inhibitory concentrations (MICs) for C.
      neoformans clinical isolates were 0.06-1.0 microg/mL for amphotericin B, 0.125-8
      microg/mL for fluconazole, 0.03-0.5 microg/mL for itraconazole and 0.03-0.25
      microg/mL for voriconazole. C. neoformans environmental isolates showed range
      MICs 0.015-0.125 microg/mL, 0.25-2.0 microg/mL, 0.007-0.125 microg/mL and 0.03
      0.25 microg/mL for amphotericin B, fluconazole, itraconazole and voriconazole
      respectively. The MICs results obtained from clinical and environmental isolates
      showed similar pattern of susceptibility and no resistance has been found in our
      isolates.

PMID- 16302108
TI  - Virulence profile of ten Paracoccidioides brasiliensis isolates: association with
      morphologic and genetic patterns.
AB  - Ten isolates of Paracoccidioides brasiliensis were examined for differences in
      virulence in outbred mice intravenously inoculated with the fungus, associated
      with mycelial morphology, and genetic patterns measured by random amplified
      polymorphic DNA (RAPD). Virulence was evaluated by viable yeast cell recovery
      from lungs and demonstration of histopathologic lesions in different organs. The
      results showed that the isolates presented four virulence degrees: high
      virulence, intermediate, low and non-virulence. RAPD clustered the isolates
      studied in two main groups with 56% of genetic similarity. Strains with low
      virulence, Pb265 or the non-virulent, Pb192, showed glabrous/cerebriform
      morphology and high genetic similarity (98.7%) when compared to the other
      isolates studied. The same was observed with Bt79 and Bt83 that shared 96%
      genetic similarity, cottony colonies and high virulence. The RAPD technique could
      only discriminate P. brasiliensis isolates according to glabrous/cerebriform or
      cottony colonies, and also high from low virulence strains. Isolates with
      intermediate virulence such as Pb18, Pb18B6, Bt32 and Bt56 showed variability in
      their similarity coefficient suggesting that RAPD was able to detect genetic
      variability in this fungal species. Virulence profile of P. brasiliensis
      demonstrated that both mycelial morphologic extreme phenotypes may be associated
      with fungal virulence and their in vitro subculture time. Thus, RAPD technique
      analysis employed in association with virulence, morphologic and immunologic
      aspects might prove adequate to detect differences between P. brasiliensis
      isolates.

PMID- 16302109
TI  - Inhibitory effect of deferoxamine on Paracoccidioides brasiliensis survival in
      human monocytes: reversal by holotransferrin not by apotransferrin.
AB  - The mechanisms used by Paracoccidioides brasiliensis to survive into phagocytic
      cells are not clear. Cellular iron metabolism is of critical importance to the
      growth of several intracellular pathogens whose capacity to multiply in
      mononuclear phagocytes is dependent on the availability of intracellular iron.
      Thus, the objective of this paper was to investigate the role of intracellular
      iron in regulating the capacity of P. brasiliensis yeast cells to survive within
      human monocytes. Treatment of monocytes with deferoxamine, an iron chelator,
      suppressed the survival of yeasts in a concentration-dependent manner. The effect
      of deferoxamine was reversed by iron-saturated transferrin (holotransferrin) but
      not by nonsaturated transferrin (apotransferrin). These results strongly suggest
      that P. brasiliensis survival in human monocytes is iron dependent.

PMID- 16302110
TI  - Failure of nitric oxide production by macrophages and decrease in CD4+ T cells in
      oral paracoccidioidomycosis: possible mechanisms that permit local fungal
      multiplication.
AB  - Paracoccidioidomycosis is a chronic granulomatous disease that induces a specific
      inflammatory and immune response. The participation of nitric oxide (NO), a
      product of the inducible nitric oxide synthase enzyme (iNOS), as an important
      fungicidal molecule against Paracoccidioides brasiliensis has been demonstrated.
      In order to further characterize the Oral Paracoccidioidomycosis (OP), we
      undertook an immunohistochemical study of iNOS+, CD45RO+, CD3+, CD8+, CD20+,
      CD68+ cells and mast cells. The samples were distributed in groups according to
      the number of viable fungi per mm2. Our results showed weak immunolabeling for
      iNOS in the multinucleated giant cells (MNGC) and in most of the mononuclear (MN)
      cells, and the proportion of iNOS+ MN/MNGC cells in the OP were comparable to
      Control (clinically healthy oral tissues). Additionally, our analysis revealed a
      similarity in the number of CD4+ cells between the Control and the OP groups with
      higher numbers of fungi. These findings suggest that a low expression of iNOS and
      a decrease in the CD4+ T cells in OP may represent possible mechanisms that
      permit the local fungal multiplication and maintenance of active oral lesions.

PMID- 16302111
TI  - Co-infection between influenza virus and flagellated bacteria.
AB  - Trypsin is required in the hemagglutinin (HA) cleavage to in vitro influenza
      viruses activation. This HA cleavage is necessary for virus cell entry by
      receptor-mediated endocytosis. Bacteria in the respiratory tract are potential
      sources of proteases that could contribute to the cleavage of influenza virus in
      vivo. From 47 samples collected from horses, pigs, and from humans, influenza
      presence was confirmed in 13 and these samples demonstrated co-infection of
      influenza with flagellated bacteria, Stenotrophomonas maltophilia from the
      beginning of the experiments. Despite treatment with antibiotics, the bacteria
      remained resistant in several of the co-infected samples (48.39%). These
      bacteria, considered opportunistic invaders from environmental sources, are
      associated with viral infections in upper respiratory tract of hosts. The
      protease (elastase), secreted by Stenotrophomonas maltophilia plays a role in the
      potentiation of influenza virus infection. Proteolytic activity was detected by
      casein agar test. Positive samples from animals and humans had either a
      potentiated influenza infectivity or cytopathic effect (CPE) in MDCK and NCI H292
      cells, Stenotrophomonas maltophilia were always present. Virus and bacteria were
      observed ultrastructurally. These in vitro findings show that microbial proteases
      could contribute to respiratory complications by host protease activity
      increasing inflammation or destroying endogenous cell protease inhibitors.

PMID- 16302112
TI  - St. Louis encephalitis virus: first isolation from a human in Sao Paulo State,
      Brazil.
AB  - This paper reports the isolation of St. Louis encephalitis virus (SLEV) from a
      febrile human case suspected to be dengue, in Sao Pedro, Sao Paulo State. A MAC
      ELISA done on the patient's acute and convalescent sera was inconclusive and
      hemagglutination inhibition test detected IgG antibody for flaviviruses. An
      indirect immunofluorescent assay done on the C6/36 cell culture inoculated with
      the acute serum was positive for flaviviruses but negative when tested with
      dengue monoclonal antibodies. RNA extracted from the infected cell culture
      supernatant was amplified by RT-PCR in the presence of NS5 universal flavivirus
      primers and directly sequenced. Results of BLAST search indicated that this
      sequence shares 93% nucleotide similarity with the sequence of SLEV (strain
      MSI.7), confirmed by RT-PCR performed with SLEV specific primers. Since SLEV was
      identified as the cause of human disease, it is necessary to improve surveillance
      in order to achieve early detection of this agent in the state of Sao Paulo and
      in Brazil. This finding is also an alert to health professionals about the need
      for more complete clinical and epidemiological investigations of febrile
      illnesses as in the reported case. SLEV infections can be unrecognized or
      confused with other ones caused by an arbovirus, such as dengue.

PMID- 16302113
TI  - Rotavirus serotypes and electropherotypes identified among hospitalised children
      in Sao Luis, Maranhao, Brazil.
AB  - During June 1997-June 1999 rotavirus infection was screened in infants aged up to
      2 years and hospitalised with acute diarrhoea in Sao Luis, Northeastern Brazil.
      Altogether, 128 stool samples were collected from diarrhoeic patients and
      additional 122 faecal specimens from age and temporal matched inpatients without
      diarrhoea were obtained; rotavirus positivity rates for these groups were 32.0%
      (41/128) and 9.8% (12/122), respectively (p < 0.001). Both electropherotyping and
      serotyping could be performed in 42 (79.2%) of the 53 rotavirus-positive stool
      samples. Long and short electropherotypes were detected at similar rates--38.1%
      and 40.5% of specimens, respectively. Overall, a G serotype could be assigned for
      35 (83.3%) of specimens, the majority of them (66.7%) bearing G1-serotype
      specificity. Taking both electropherotypes and serotypes together, G1 rotavirus
      strains displaying long and short RNA patterns accounted for 30.9% and 19.0% of
      tested specimens, respectively; all G2 strains had short electropherotype.
      Rotavirus gastroenteritis was detected year-round and, in 1998, the incidence
      rates tended to be higher during the second semester than in the first semester:
      45.2% and 26.1% (p = 0.13), respectively. Rotavirus infections peaked at the
      second semester of life with frequencies of 30.1% and 13.5% for diarrhoeic
      children and controls, respectively. While the six rotavirus strains bearing G2
      type specificity were circulating throughout the whole study period, G1 serotypes
      (n = 27) emerged as from June 1998 onwards, 20 (74.1%) of which clustering in
      1998. These data underscore the importance of rotaviruses in the aetiology of
      severe infantile gastroenteritis in Northeastern Brazil and sustain the concept
      that a future vaccine should confer protection against more than one serotype.

PMID- 16302114
TI  - Optimization of random amplified polymorphic DNA techniques for use in genetic
      studies of Cuban Triatominae.
AB  - Random amplified polymorphic DNA (RAPD) technique is a simple and reliable method
      to detect DNA polymorphism. Several factors can affect the amplification
      profiles, thereby causing false bands and non-reproducibility of assay. In this
      study, we analyzed the effect of changing the concentration of primer, magnesium
      chloride, template DNA and Taq DNA polymerase with the objective of determining
      their optimum concentration for the standardization of RAPD technique for genetic
      studies of Cuban Triatominae. Reproducible amplification patterns were obtained
      using 5 pmoL of primer, 2.5 mM of MgCl2, 25 ng of template DNA and 2 U of Taq DNA
      polymerase in 25 microL of the reaction. A panel of five random primers was used
      to evaluate the genetic variability of T. flavida. Three of these (OPA-1, OPA-2
      and OPA-4) generated reproducible and distinguishable fingerprinting patterns of
      Triatominae. Numerical analysis of 52 RAPD amplified bands generated for all five
      primers was carried out with unweighted pair group method analysis (UPGMA).
      Jaccard's Similarity Coefficient data were used to construct a dendrogram. Two
      groups could be distinguished by RAPD data and these groups coincided with
      geographic origin, i.e. the populations captured in areas from east and west of
      Guanahacabibes, Pinar del Rio. T. flavida present low interpopulation variability
      that could result in greater susceptibility to pesticides in control programs.
      The RAPD protocol and the selected primers are useful for molecular
      characterization of Cuban Triatominae.

PMID- 16302115
TI  - Infection by Cryptosporidium sp. in immunocompromised haematological patients.
AB  - The frequency of intestinal infection by Cryptosporidium sp. was determined in 60
      patients, attended at the Haematological and Haemotherapeutical Service of "Santa
      Casa de Misericordia" of Sao Paulo, suffering lymphoproliferative diseases (Group
      1). As control group (Group 2) 59 persons without haematological diseases, but
      with the same life time and living at the same place of that of haematological
      patients, had been examined. The stool parasitological tests performed disclosed
      Cryptosporidium sp. oocysts in six (10%) individuals belonging to Group 1,
      whereas, in Group 2, nobody showed infection by this coccidian. Among the
      patients infected by Cryptosporidium sp. only one showed diarrhoeal faeces.

PMID- 16302116
TI  - Severe Pneumocystis pneumonia in a renal transplant recipient after long term
      mycophenolate mofetil treatment.

PMID- 16302117
TI  - [Current imaging in Takayasu arteritis].

PMID- 16302127
TI  - [The future of radiology -- from the necessity of a vision].

PMID- 16302128
TI  - [Comment to the editorial].

PMID- 16302129
TI  - Initial clinical results with a new needle screen storage phosphor system in
      chest radiograms.
AB  - PURPOSE: To evaluate image quality and anatomical detail depiction in dose
      reduced digital plain chest radiograms using a new needle screen storage phosphor
      (NIP) in comparison to full dose conventional powder screen storage phosphor
      (PIP) images. MATERIALS AND METHODS: 24 supine chest radiograms were obtained
      with PIP at standard dose and compared to follow-up studies of the same patients
      obtained with NIP with dose reduced to 50 % of the PIP dose (all imaging systems:
      AGFA-Gevaert, Mortsel, Belgium). In both systems identical versions of post
      processing software supplied by the manufacturer were used with matched
      parameters. Six independent readers blinded to both modality and dose evaluated
      the images for depiction and differentiation of defined anatomical regions
      (peripheral lung parenchyma, central lung parenchyma, hilum, heart, diaphragm,
      upper mediastinum, and bone). All NIP images were compared to the corresponding
      PIP images using a five-point scale (- 2, clearly inferior to + 2, clearly
      superior). Overall image quality was rated for each PIP and NIP image separately
      (1, not usable to 5, excellent). RESULTS: PIP and dose reduced NIP images were
      rated equivalent. Mean image noise impression was only slightly higher on NIP
      images. Mean image quality for NIP showed no significant differences (p > 0.05,
      Mann-Whitney U test). CONCLUSION: With the use of the new needle structured
      storage phosphors in chest radiography, dose reduction of up to 50 % is possible
      without detracting from image quality or detail depiction. Especially in patients
      with multiple follow-up studies the overall dose can be decreased significantly.

PMID- 16302130
TI  - [MR imaging in cardiomyopathies].
AB  - According to the WHO classification, cardiomyopathies are a group of diseases
      which are associated with myocardial dysfunction and can be classified either as
      primary or secondary cardiomyopathies. Genetic disorders have been identified in
      certain primary cardiomyopathies, however often the etiology remains unknown. The
      term "secondary cardiomyopathy" is used to specify diseases with the clinical
      indications of a cardiomyopathy, but can be attributed to a certain
      pathophysiological mechanism such as exposure to toxic substances, metabolic
      syndromes or systemic diseases. Based on morphological and functional criteria,
      primary cardiomyopathies are divided into dilated cardiomyopathy (DCM),
      hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular
      cardiomyopathy (ARVC) and restrictive cardiomyopathy (RCM). During the last two
      decades MR imaging has emerged to a well established diagnostic tool for the
      understanding and treatment of cardiomyopathies. Morphological and functional
      information can be achieved with a high level of accuracy and reproducibility.
      Tissue alteration of the myocardium can be detected assessing regional contrast
      enhancement, T1- and T2-signal intensities and chemical shift phenomena. This
      article describes characteristic aspects of MR imaging for the diagnosis of
      primary and secondary cardiomyopathies.

PMID- 16302131
TI  - [Radiologic features of inflammatory pseudotumors].
AB  - Inflammatory pseudotumor is a rare benign tumor entity. Because inflammatory
      pseudotumors mimic malignant tumors both clinically and radiologically, the
      radiologist should be familiar with this entity. Inflammatory pseudotumor most
      commonly involves the lung and the orbit, but it has been reported to occur in
      nearly every site in the body. For making a definite diagnosis a biopsy is often
      essential. The treatment options are varied and consist of surgery, high-dose
      steroids, irradiation, and chemotherapeutics.

PMID- 16302132
TI  - [Thoracic real-time MRI: experience from 2200 examinations in acute and ill
      defined thoracic diseases].
AB  - PURPOSE: To retrospectively assess the indication for thoracic real-time MRI,
      demonstrate typical findings, analyze the diagnostic potential in subgroups with
      suspected pulmonary embolism (PE) and aortic dissection (AD), and describe the
      influence of real-time MRI on the role of MRI in acute thoracic diseases.
      MATERIALS AND METHODS: From July 2001 to February 2005, real-time MRI was applied
      in 2,256 examinations in 1,714 patients. MRI was the primary diagnostic modality
      for these thoracic diseases as computed tomography has been available only since
      2003. Characteristics of the TrueFISP sequence applied were: TR/TE/flip angle 3.1
      ms/1.6 ms/59 degrees , respectively. FOV 340 - 360 mm, matrix size 156 to 192 x
      256 pixels, slice thickness 3 to 4 mm, slices overlapped by 50 %. Acquisition
      time was 0.4 to 0.5 s per image. Three hundred and twenty transverse, coronal and
      sagittal images were acquired in three minutes. No breath holding, and only
      minimal patient cooperation, was required. Turbo-spin-echo sequences as well as
      ECG-gated and contrast-enhanced sequences were added depending on the indication.
      RESULTS: Most common indications were: acute thoracic nonspecified disease (n =
      276, 12.24 %), PE (n = 573, 25.4 %), bleeding (n = 154, 6.8 %), AD (n = 222, 9.8
      %), topographic information in complex findings (n = 654, 29.0 %). Real-time MRI
      was the sole MRI technique applied in 180 examinations (8.0 %), ECG-gated real
      time MRI was applied in 87 examinations and breath hold was used in 107
      examinations. PE was diagnosed in 181 examinations; reference techniques (MRI,
      computed tomography, single photon emission computed tomography) confirmed 170 of
      these and detected 19 more cases (sensitivity 90.0 %, specificity 97.1 %). Real
      time MRI detected 141 suspected AD and 53 more nonsuspected AD. Of these, 191
      were confirmed by other MRI techniques, surgery or clinical course (98.5 %). Real
      time MRI coincidentally detected 56 pulmonary tumors, all were confirmed with
      computed tomography. Thus, especially vascular diseases could be easily assessed
      with real-time MRI, while computed tomography had advantages in the evaluation of
      the lung parenchyma. CONCLUSION: Real-time MRI both enables emergency MRI
      examinations for thoracic diseases in clinical patients in unstable condition and
      allows an explorative style of working in patients with nondefined acute thoracic
      diseases.

PMID- 16302133
TI  - [Preoperative mapping of speech-eloquent areas with functional magnetic resonance
      imaging (fMRI): comparison of different task designs].
AB  - PURPOSE: Functional magnetic resonance imaging (fMRI) is a well-established, non
      invasive method for pre-operative mapping of speech-eloquent areas. This
      investigation tests three simple paradigms to evaluate speech lateralisation and
      visualisation of speech-eloquent areas. MATERIALS AND METHODS: 14 healthy
      volunteers and 16 brain tumour patients were given three tasks: to enumerate
      months in the correct order (EM), to generate verbs fitting to a given noun (GV)
      and to generate words fitting to a given alphabetic character (GW). We used a
      blocked design with 80 measurements which consisted of 4 intervals of speech
      activation alternating with relaxation periods. The data were analysed on the
      basis of the general linear model using Brainvoyager(R). The activated clusters
      in the inferior frontal (Broca) and the posterior temporal (Wernicke) cortex were
      analysed and the laterality indices calculated. RESULTS: In both groups the
      paradigms GV and GW activated the Broca's area very robustly. Visualisation of
      the Wernicke's area was best achieved by the paradigm GV. The paradigm EM did not
      reliably stimulate either the frontal or the temporal cortex. Frontal
      lateralisation was best determined by GW and GV, temporal lateralisation by GV.
      CONCLUSION: The paradigms GV and GW visualise two essential aspects of speech
      processing: semantic word processing and word production. In a clinical setting
      with brain tumour patients, both, GV and GW can be used to visualise frontal and
      temporal speech areas, and to determine speech dominance.

PMID- 16302134
TI  - [Incidence of cerebral ischemia in patients with suspected cervical artery
      dissection: first results of a prospective study].
AB  - PURPOSE: Aim of this prospective study was to investigate the incidence of
      spontaneous cervical artery dissection (sCAD) and cerebral ischemia in patients
      with suspected sCAD by using a combined head-neck MR-imaging protocol. MATERIALS
      AND METHODS: 51 consecutive patients (24 m, 27 f, mean age 39.5 years, range 18 -
      55 yrs) admitted to our stroke unit with suspected sCAD according to clinical
      criteria and age < 55 years underwent a combined head and neck MR examination
      within 24 hours of admission (Gyroscan Intera 1.5 T, Philips). Head MRI included
      ax FLAIR, ax T (1), ax DWI and TOF angiography (imaging time 12 min). Neck MRI
      consisted of ax T1w-TSE, T2w-TSE, contrast enhanced T1w-TSE and CE-MRA (imaging
      time 17 min). Three radiologists assessed both studies in consensus with regard
      to the presence of sCAD and acute ischemia. RESULTS: One patient had to be
      excluded because of motion artefacts. In 17 of 50 patients sCAD was diagnosed,
      and in 20 of 50 patients cerebral ischemia. In 5 patients cerebral ischemia was
      caused by sCAD. CONCLUSION: The proposed combined MR protocol allows imaging work
      up of patients with suspected sCAD within approximately 30 min, resulting in
      conclusive information about the status of the extracranial vasculature and the
      presence of ischemia. The high incidence of patients with definite sCAD and the
      low incidence of cerebral ischemia indicates the necessity of an early definite
      diagnosis in order to start timely anticoagulation to prevent development of
      stroke.

PMID- 16302136
TI  - [Diagnostic mammography and sonography: concordance of the breast imaging
      reporting assessments and final clinical outcome].
AB  - PURPOSE: The purpose of the study was to assess the final clinical outcome of BI
      RADS Categories for diagnostic mammography and sonography. MATERIAL AND METHODS:
      We analysed 632 mammography and sonography examinations from women with
      diagnostic indications (age: 23 - 100, mean 58) performed during 2001 and 2003.
      All patients received mammography and sonography examinations at different
      outside facilities and all patients received an additional sonography examination
      at the university radiology department and if necessary supplemental mammographic
      views. Final clinical outcome (Histology: 554; follow-up: 78) was ascertained in
      each case and concordance of BI-RADS-categories for mammography and sonography
      and final diagnosis were analysed. RESULTS: Final diagnosis yielded 230 benign
      lesions (36 %) and 402 cancers (64 %). Concordance of BI-RADS Assessment and
      final outcome was documented in 542 cases (86 %). There were 11 correct category
      1 and 2 assessments (2 %). 142 lesions were classified with BI-RADS 3 (22 %) with
      5 false negative ratings. There were 264 category 4 lesions (42 %) with a PPV for
      a malignant lesion of 71 % (187/264) and finally 215 BI-RADS 5 lesions with a PPV
      of 98 % (210/215). Overall sensitivity of mammography was 92 % with specificity
      of 75 % and for sonography 86 % and 76 %. Mammography had a significantly higher
      detection rate for malignant lesions than sonography. The highest correlation
      between BI-RADS category and final outcome was documented for the diagnostic
      combination of mammography and sonography with a kappa-value of 0.817 (p <
      0.001), followed by mammography (kappa: 0.684) and sonography (kappa: 0.631). The
      overall correlation was 0.681 (p < 0.001). CONCLUSION: BI-RADS assessments of
      diagnostic mammography and sonography yields in a high cancer detection rate with
      a justifiable part of false positive ratings.

PMID- 16302135
TI  - [Clinical relevance of multislice CT of the spine after osteosynthesis].
AB  - PURPOSE: To examine the clinical relevance of multislice CT (MSCT) scans in
      postoperative checks of the spine after osteosynthesis. MATERIAL AND METHODS: The
      results of x-rays (apical lateral) in 30 patients having spinal surgery involving
      osteosynthesis (5 x metastasis, 20 x fractures, 3 x spondylolisthesis, 2 x
      scoliosis) were correlated to those of MSCT (140 kV, 200 mAs, collimation 4 x 1
      mm, pitch 0.75; VolumeZoom, Siemens, Erlangen, Germany) with multiplanar
      reconstruction. Two radiologists independently checked the conventional x-ray and
      multislice CT scans for anatomical positioning, damage of osteosynthetic
      material, and intraspinal dislocation of bone fragments. RESULTS: By correlating
      conventional spinal x-rays with MSCT, additional diagnostic information was
      gained. In 9 of 30 patients MSCT revealed the extraosseal location of a screw tip
      (x-ray, 5/30), in 8/30 patients a narrowing of the spinal canal by osteosynthetic
      material was detected in MSCT (x-ray, 4/30), in 2/30 patients osteal fragments
      were detected in the vertebral canal by MSCT (x-ray, 0/30). In MSCT and in
      conventional x-ray a fracture of the osteosynthesis was correctly diagnosed in 3
      patients. One patient underwent corrective surgery for dislocated osteosynthetic
      material, which was solely diagnosed with MSCT. CONCLUSION: Due to the high
      degree of additional diagnostic information MSCT seems to be the method of choice
      for postoperative spinal surgery involving osteosynthesis.

PMID- 16302137
TI  - [Cortical reorganization in children with connatal spastic hemiparesis -- a
      functional magnetic resonance imaging (FMRI) study].
AB  - PURPOSE: We applied fMRI to investigate atypical cortical activation in patients
      with connatal spastic hemiparesis using voluntary movements of the hand, foot,
      and tongue. The relation between the findings from fMRI and the motor dysfunction
      was examined. MATERIALS AND METHODS: 11 patients with connatal spastic
      hemiparesis were studied. Eight of these patients had periventricular
      leukomalacia (PVL), and three patients had cortical-subcortical lesions. To
      evaluate the severity of motor impairment tests for the upper and lower limb were
      performed. fMRI data were obtained in a block design using hand, foot, and tongue
      movements. As a control group, 14 healthy volunteers were examined with the fMRI
      protocol. RESULTS: A laterally cortical representation of the paretic foot was
      found in three patients with PVL. In patients with cortical-subcortical lesions,
      tongue movements were associated with cortical activation restricted to the
      unaffected hemisphere. Movements of the paretic limb showed more ipsilateral
      activation in patients with PVL than in patients with cortical-subcortical
      lesions. CONCLUSION: Different types of structural damage such as PVL and
      cortical-subcortical lesions show differences in fMRI examination.

PMID- 16302138
TI  - [16-row multidetector CT angiography of the aortoiliac system and lower extremity
      arteries: contrast enhancement and image quality using a standarized examination
      protocol].
AB  - PURPOSE: To assess the degree of enhancement and image quality of 16-slice
      multidetector CT angiography (MDCTA) of pelvic and lower limb arteries with a
      monophasic contrast medium injection protocol. MATERIALS AND METHODS: Fifty
      patients underwent a CT angiography of the pelvic and lower limb arteries using
      the following parameters: collimation 16 x 1.5 mm, rotation time 0.5 s, table
      feed 40 mm/sec, slice thickness 2 mm, reconstruction interval 1.2 mm, 100 ml
      Iomeprol 400 + 60 ml normal saline, flow rate 4 ml/s, bolus tracking (threshold
      of 250 DeltaHU in aorta). Arterial enhancement was measured in all arterial
      segments. Maximum intensity projections (MIP) together with axial images were
      reviewed by two radiologists (consensus). If the results were inconclusive for
      stenosis, additional curved multiplanar reformations (MPR) were performed.
      RESULTS: The mean arterial enhancement values were aorta: 314 +/- 69, pelvis: 342
      +/- 105, thigh: 347 +/- 139, calf: 231 +/- 109 DeltaHU. The image quality was
      judged as excellent in 346 (77.6 %), adequate in 76 (17 %), and inadequate in 24
      (5.4 %, all but one in calf and foot) of 446 arterial territories. An override of
      the contrast bolus below the knee occurred in 2 patients rendering the calf
      arteries nondiagnostic. Venous enhancement occurred in 13 patients but this
      compromised the diagnostic assessment in only one case. Additional MPRs were
      required accurately to assess stenoses in 22 of 200 arterial levels in 16
      patients with marked arterial calcifications. CONCLUSION: 16-slice MDCTA with a
      monophasic contrast bolus of Iomeprol 400 provided good arterial enhancement and
      diagnostic image quality in 94.6 % of the depicted arterial segments. The
      majority (67 %) of nondiagnostic segments were below the ankle. MPRs were
      required in patients with marked calcification for accurate assessment of
      stenosis.

PMID- 16302139
TI  - [Differential diagnosis of focal liver lesions using contrast-enhanced MRI with
      SHU 555 A in comparison with unenhanced MRI and multidetector spiral-CT].
AB  - PURPOSE: To evaluate the ability of contrast-enhanced MRI with SHU 555 A to
      provide additional information for characterization of focal liver tumors
      compared with non-enhanced MRI and multislice spiral CT. MATERIALS AND METHODS:
      In a prospective manner the images of 45 patients who underwent multislice spiral
      CT, unenhanced MRI alone and unenhanced and SHU 555 A-enhanced MRI including
      dynamic imaging at a field strength of 1.0 T were analyzed in a blinded reading.
      The readers had to determine on a scale from 1 to 5 whether a tumor was benign or
      malignant. Furthermore, the readers had to give a definitive diagnosis for each
      lesion. A true cut needle biopsy served as gold standard against which all
      imaging procedures were compared. RESULTS: The sensitivity for differentiation
      malignant vs. benign lesion was 77 % with spiral CT, 72 % with unenhanced MRI and
      94 % with SHU 555 A-enhanced MRI, respectively (p < 0.05). The specificity for
      spiral CT was 73 %, for unenhanced MRI 83 % and for contrast-enhanced MRI 83 %,
      respectively (n. s.). Compared with the histopathologic results, the correct
      diagnosis was made with spiral CT in 25/45 (56 %), unenhanced MRI in 16/45 (36 %)
      and contrast-enhanced MRI in 32/45 (71 %) of the patients (p < 0.05). For the
      subgroup of patients with liver cirrhosis, the correct diagnosis was established
      with spiral CT in 16/23 (70 %), unenhanced MRI in 9/23 (39 %) and contrast
      enhanced MRI in 19/23 (83 %) of the patients (p < 0.05). CONCLUSION: Contrast
      enhanced MRI with SHU 555 A has the ability to improve the differential diagnosis
      of focal liver tumors compared with unenhanced MRI and multislice spiral CT.

PMID- 16302140
TI  - [Left ventricular pseudoaneurysm with subcutaneous herniation in an adult patient
      with complex heart defect].

PMID- 16302141
TI  - [Juvenile bone cyst, osteochondroma and non-ossifying fibroma in a male patient.
      A case report with description of entities].

PMID- 16302142
TI  - [Infratentorial progressive multifocal leukoencephalopathy in a patient with
      pulmonary sarcoidosis].

PMID- 16302143
TI  - [Secondary osteonecrosis: steroid therapy and its possible sequelae].

PMID- 16302144
TI  - [Benign mediastinal schwannoma of the left supraaortic branch of the vagus
      nerve].

PMID- 16302151
TI  - Fibrin D-dimer testing for venous and arterial thrombotic disease.

PMID- 16302152
TI  - Validation, calibration, and specificity of quantitative D-dimer assays.
AB  - Assays for D-dimer antigen are based on monoclonal antibodies reactive with
      epitopes found on fibrin fragment D-dimer but not on fibrinogen fragment D, other
      fibrinogen degradation products, or native fibrinogen. The antibodies react with
      conformational epitopes generated by factor XIII-induced linkage of the C
      terminal appendages of the fibrin gamma-chains of adjacent D-domains within a
      fibrin polymer. For some monoclonal antibodies, degradation of the cross-linked
      fibrin compound by plasmin is an additional requirement for the generation of the
      epitope. In clinical plasma samples, D-dimer antigen assays detect an array of
      fibrin compounds of different molecular weights, including fibrin fragment D
      dimer as well as higher-molecular-weight fibrin degradation products and fibrin X
      oligomers. Most D-dimer antigen represents cross-linked soluble fibrin present in
      circulation rather than degradation products from particulate clots. Due to
      differences in epitope reactivity, harmonization of D-dimer antigen assays can
      only be achieved with standard preparations containing a similar variety of cross
      linked fibrin compounds. Assay technologies include manual latex agglutination
      assays, automated latex-enhanced light-scattering immunoassays, enzyme-linked
      immunoassays, and others.

PMID- 16302153
TI  - The harmonization of quantitative test results of different D-dimer methods.
AB  - Nowadays D-dimer testing is frequently applied in the diagnosis of venous
      thromboembolism. However, the test results of different quantitative D-dimer
      tests can differ significantly. The background of this variability, which is
      mainly caused by the variety of fibrin degradation products in plasma, the
      specificity of D-dimer assays, and the calibrators used in the test, is
      summarized here. Because D-dimer is not a single entity in plasma but a mixture
      of heterogeneous fibrin degradation products, method standardization is in
      principle impossible. Efforts undertaken in the past to standardize D-dimer
      methods are summarized. All these projects failed and it was concluded that only
      harmonization of D-dimer test results seems to be feasible. The results of a
      large field study on which a new approach to the harmonization of quantitative D
      dimer methods will be based is summarized in this article. This approach seems to
      be an adequate solution for overcoming the practical problem of variation of test
      outcome in different D-dimer assays.

PMID- 16302154
TI  - Comparability of D-dimer assays in clinical samples.
AB  - D-dimers (DD) have shown sufficient proof of their efficiency in the last 10
      years to play an important role in hemostasis laboratories for excluding
      thromboembolic events. Numerous reagents are available on the market but their
      performances differ. This overview takes stock of the methods used to evaluate
      the performances of DD assays, the results published in the literature, the
      technical parameters influencing assay performance, the difficulties caused by
      the lack of harmonization of DD units, and the attempts to tackle this problem.
      It raises the issue of the potential optimization of their use with regard to
      better adaptation to multidisciplinary diagnostic strategies and to target
      patient populations.

PMID- 16302155
TI  - The role of qualitative D-dimer assays, clinical probability, and noninvasive
      imaging tests for the diagnosis of deep vein thrombosis and pulmonary embolism.
AB  - Recent advances in the management of patients with suspected venous
      thromboembolism have both improved diagnostic accuracy as well as made management
      algorithms safer and more accessible. It is now clear that determination of
      clinical probability prior to diagnostic testing will improve patient management.
      D-dimer testing can be employed to decrease the need for imaging tests. Patients
      at low risk with a negative qualitative D-dimer can avoid imaging tests. Imaging
      test interpretation benefits from consideration of pretest probability also as
      this helps clinicians determine when a test may be falsely negative or falsely
      positive. Diagnostic strategies should include pretest clinical probability, D
      dimer assays, and noninvasive imaging tests.

PMID- 16302156
TI  - Screening for deep vein thrombosis and pulmonary embolism in outpatients with
      suspected DVT or PE by the sequential use of clinical score: a sensitive
      quantitative D-dimer test and noninvasive diagnostic tools.
AB  - The requirement for a safe diagnostic strategy should be based on an overall
      posttest incidence of venous thromboembolism (VTE) of less than 1% during 3-month
      follow-up. The negative predictive value (NPV) during 3 months of follow-up is
      98.1 to 99% after a normal venogram, 97 to 98% after a normal compression
      ultrasonography (CUS), and > 99% after serial CUS testing. Serial CUS testing is
      safe but 100 CUS must be repeated to find one or two CUS positive for deep vein
      thrombosis (DVT), which is not cost-effective and indicates the need to improve
      the diagnostic workup of DVT by the use of clinical score assessment and D-dimer
      testing. The NPV varies from 97.6 to 99.4% for low clinical score followed by a
      negative SimpiRED test, indicating the need for a first CUS. The NPV is 98.4 to
      99.3% for a normal rapid enzyme-linked immunosorbent assay (ELISA) VIDAS D-dimer
      test result (< 500 ng/mL) irrespective of clinical score. The NPV is more than
      99% for a negative CUS followed by either a negative SimpiRED test or an ELISA
      VIDAS test result of < 1000 ng/mL without the need to repeat a second CUS within
      1 week. The sequential use of a sensitive, rapid ELISA D-dimer and clinical score
      assessment will safely reduce the need for CUS testing by 40 to 60%. Large
      prospective outcome studies demonstrate that with one negative examination with
      complete duplex color ultrasonography (CCUS) of the proximal and distal veins of
      the affected leg with suspected DVT, it is safe to withhold anticoagulant
      treatment, with a negative predictive value of 99.5%. This may indicates that
      CCUS is equal to serial CUS or the combined use of clinical score, D-dimer
      testing, and CUS. Pulmonary angiography is the gold standard for segmental
      pulmonary embolism (PE) but not for subsegmental PE. A normal perfusion lung scan
      and a normal rapid ELISA VIDAS D-dimer test safely excludes PE. Helical spiral
      computed tomography (CT) detects all clinically relevant PE and a large number of
      alternative diagnoses in symptomatic patients with suspected PE and can replace
      both the ventilation perfusion scan and pulmonary angiography to safely rule in
      PE and to rule out PE with an NPV of > 99%. The combination of clinical
      assessment, a rapid ELISA VIDAS D-dimer, followed by CUS will reduce the need for
      helical spiral CT by 40 to 50%.

PMID- 16302157
TI  - D-dimer, oral anticoagulation, and venous thromboembolism recurrence.
AB  - Venous thromboembolism (VTE) requires prolonged treatment to prevent late
      recurrences. However, the optimal duration of vitamin K antagonist (VKA) therapy
      is still controversial. More recently, D-dimer (D-d) has emerged as a predictive
      factor for recurrences. D-d has been evaluated both during and after VKA
      treatment. Some patients with DVT of the lower limbs have persistently high D-d
      during anticoagulation and this could reflect insufficient anticoagulation
      despite apparently adequate antithrombotic treatment. Altered D-d during
      anticoagulation is more frequent in patients with idiopathic or cancer-associated
      VTE than in those with secondary VTE. In subjects with an unprovoked VTE event,
      the time spent at near normal international normalization ratio (INR) values (<
      1.5) during the first 3 months of treatment is associated with higher D-d during
      and after VKA treatment and with a higher risk for late recurrences. Moreover,
      the combination of altered D-d and inherited thrombophilia, and not residual
      venous obstruction, is associated with a significantly higher hazard ratio for
      recurrence. Preliminary results of a management study, the PROLONG study,
      indicate that subjects with normal D-d at 1 month after VKA withdrawal have a low
      risk of recurrence, and those with altered D-d have a significantly higher risk
      and deserve prolonged treatment.

PMID- 16302158
TI  - D-dimer levels, constitutional thrombophilia, and venous thrombosis prediction:
      clinical aspects and implications.
AB  - The negative predictive value of D-dimers in the diagnosis of a recent venous
      thromboembolism (VTE) episode is well established. The plasma level of D-dimer is
      usually increased in hypercoagulable states. The measurement of D-dimer could be
      of clinical interest in patients with constitutional thrombophilia as there is no
      close relationship between the clinical expression and the genotype indicating
      the existence of a hypercoagulable state. Moreover, the predictive value of D
      dimer testing in patients with thrombophilia has been questioned. The review of
      the literature and results of a recent study of our group are presented.
      Decreased levels of D-dimer are observed in patients receiving an oral
      anticoagulant treatment versus untreated patients. In contrast, no significant
      difference was observed between those with and those without thrombophilia among
      treated or untreated patients. Patients with constitutional thrombophilia are
      supposed to have an increased risk of postoperative VTE. The review of the
      existing literature could not confirm this opinion but this could be due to the
      fact that most patients receive a prophylactic treatment. Thus, there is an
      indirect evidence of its efficacy in these patients.

PMID- 16302159
TI  - D-dimer testing in pregnancy.
AB  - Normal pregnancy is associated with alterations of the hemostatic system toward a
      hypercoagulable state. Elevated markers of coagulation and fibrinolytic system
      activation, such as D-dimer, indicate increased thrombin activity and increased
      fibrinolysis following fibrin formation throughout pregnancy. Testing for D-dimer
      in pregnant women could be useful for the diagnosis and prediction of a venous
      thromboembolic event or pregnancy-related complications and for monitoring
      antithrombotic treatment. This approach, however, is hampered by the fact that
      even an uncomplicated pregnancy in healthy women is accompanied by a substantial
      increase of D-dimer. Thus, prior to clinical application reference values of D
      dimer according to gestational age need to be validated. A substantial increase
      of D-dimer during pregnancy is seen despite thromboprophylaxis with low-molecular
      weight heparin (LMWH), indicating that further studies are needed to evaluate
      monitoring of LMWH during pregnancy and to investigate the optimal beginning and
      dose of LMWH thromboprophylaxis in pregnant women.

PMID- 16302160
TI  - D-dimer testing in ischemic stroke and cerebral sinus and venous thrombosis.
AB  - D-dimer measurement is commonly included in the diagnostic workup of patients
      with suspected acute symptomatic deep venous thrombosis and pulmonary embolism.
      As a haemostatic marker, it could be theoretically useful in other thromboembolic
      disorders, such as acute cerebrovascular events. In this review we summarize
      published literature on D-dimer testing in acute ischemic stroke and cerebral
      sinus and venous thrombosis (CSVT), discussing possible clinical diagnostic and
      therapeutical applications. In ischemic stroke, mounting evidence suggests a
      possible role of D-dimer in the acute diagnosis of ischemic stroke subtypes,
      especially in identifying tromboembolic and lacunar stroke. Its prognostic role
      still remains unclear, due to conflicting data. D-dimer could be also an useful
      screening test for excluding CSVT in patients presenting with acute headache,
      making the presence of cerebral thrombosis unlikely with low plasma levels. In
      this clinical setting sensitivity and negative predictive value are comparable to
      that reported in the diagnosis of acute thromboembolic disease. However, more
      studies are needed to confirm these recent findings as well as management studies
      to correctly introduce D-dimer measurement in clinical daily practice of ischemic
      stroke and CSVT.

PMID- 16302161
TI  - Fibrin D-dimer and cardiovascular risk.
AB  - Fibrin D-dimer, the most commonly used clinical assay for detection of
      coagulation activation and in vivo fibrin formation and lysis in circulating
      blood, has been associated with risks of cardiovascular diseases in studies
      published over the past 15 years. This review discusses, in turn, analytic and
      preanalytic considerations; associations with risk factors; and associations with
      coronary heart disease, atrial fibrillation, stroke and cerebrovascular disease,
      peripheral arterial disease, and venous thromboembolism. These associations
      suggest that activated coagulation and in vivo fibrin formation and lysis may
      play a role in arterial, intracardiac, and venous thromboembolism. The potential
      clinical utility of D-dimer in prediction of cardiovascular risk, in indicating
      patient groups for prophylactic anticoagulation and in monitoring of
      anticoagulation, requires further study. Harmonization of results from different
      assays would increase clinical utility.

PMID- 16302162
TI  - Congenital pulmonary myofibroblastic tumor--pathology and prenatal sonographic
      appearance.

PMID- 16302163
TI  - Apert syndrome associated with increased fetal nuchal translucency.

PMID- 16302164
TI  - Prenatal diagnosis of low-level mosaic trisomy 7 by amniocentesis.

PMID- 16302165
TI  - Prenatal diagnosis of partial trisomy 10q (10q25.3-->qter) and partial monosomy
      18q (18q23-->qter).

PMID- 16302166
TI  - Hypospadias in sons of women exposed to ditheylstilbestrol: a true trans
      generational effect?

PMID- 16302167
TI  - Superoxide anion radical generation in the NaOH/H(2)O(2)/Fe(III) system: a spin
      trapping ESR study.
AB  - Formation of free radical intermediates in a NaOH/H(2)O(2)/Fe(III) system has
      been studied by ESR spectroscopy in the presence of the spin trap 5,5-dimethy-1
      pyrroline N-oxide (DMPO). DMPO/O(2(*) ) (-) and DMPO/(*)OH signals were
      simultaneously detected in this system, but only the DMPO/(*)OH signal could be
      observed in the absence of Fe(III). Effects of pH values and Fe(III)
      concentrations on the ESR signal intensities were investigated in detail.
      Formation of DMPO/O(2(*) ) (-) adduct was inhibited by the addition of superoxide
      dismutase (SOD), catalase or nitro blue tetrazolium (NBT), and by chelating the
      Fe(III) with some chelators, including ethylenediaminetetraacetic acid (EDTA),
      diethylenetriaminepentaacetic acid (DTPA), and desferrioxamine (DFO).
      Deoxygenation from the NaOH/H(2)O(2)/Fe(III) mixture had a slight effect on the
      formation of DMPO/O(2(*) ) (-). DMPO/O(2(*) ) (-) signal was also detected from
      the NaOH/H(2)O(2)/Fe(II) mixture, but it can be totally suppressed under
      anaerobic conditions. Considering the hydrolysis of Fe(III) into polymerization
      iron species with oxide phases in the alkaline medium, Fe(2)O(3) was directly
      suspended into a mixture of NaOH/H(2)O(2) for comparison. Fortunately, the
      presence of Fe(2)O(3) suspension was found to be of benefit to the production of
      DMPO/O(2(*) ) (-). Influence of aging time of hydrolytic iron species on the
      superoxide anion radical generation was also studied. These results suggest that
      the generation of O(2(*) ) (-) from the NaOH/H(2)O(2)/Fe(III) system was probably
      caused by the heterogeneous surface catalysis initiated by hydrolytic iron
      species.

PMID- 16302168
TI  - The prenatal diagnosis of cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL) by mutation analysis.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is an important cause of hereditary stroke.
      Mutations in the Notch3 gene are clearly causally linked to this progressive
      vascular disorder. Cerebral ischemic attacks, cognitive decline, strokes, and
      vascular dementia constitute the major manifestations of this disorder. This
      report details the prenatal detection of a Notch3 mutation in the fetus of a
      couple where the father had a known mutation in this gene. This is the first
      report of a prenatal diagnosis of CADASIL, and another example of a serious,
      highly penetrant, and relentlessly progressive degenerative genetic disorder
      presenting decades after birth and for which prenatal diagnosis is an option.

PMID- 16302169
TI  - Peptidyl-prolyl isomerase inhibitors.
AB  - Designed peptidyl-prolyl isomerase (PPIase) inhibitors of Pin1, cyclophilin
      (CyP), and FK506 binding protein (FKBP) are reviewed. Emphasis is placed on the
      design, structure, and biological activity of the inhibitors. While CyP and FKBP
      inhibitors have been explored fairly thoroughly, inhibitors of the relatively new
      Pin1 cell cycle regulator are in their infancy. Ligands designed for Pin1 and CyP
      have primarily been ground state analogues: alkenes and bicyclic compounds. For
      FKBP, more of the focus has been on analogues of bonds at the reactive center,
      the prolyl amide, because of the idea that the alpha-ketoamide of FK506 is an
      analogue of the twisted amide in the transition state.

PMID- 16302171
TI  - Genotoxic effects of extremely low frequency (ELF) magnetic fields (MF) evaluated
      by the Tradescantia-micronucleus assay.
AB  - Extremely low frequency (ELF) electric fields (EF) and magnetic fields (MF) are
      generated during the production, transmission, and use of electrical energy.
      Although epidemiology studies suggest that there is a cancer risk associated with
      exposure to ELF-MF, short-term genotoxicity assays with bacteria and mammalian
      cells have produced inconsistent results. In the present study, we investigated
      the possible genotoxicity of ELF-MF by using the Tradescantia-micronucleus (Trad
      MN) assay, a sensitive, reproducible, well-standardized assay for genotoxicity
      testing. A 50 Hz ELF-MF was generated by a laboratory exposure system consisting
      of a pair of parallel coils in a Helmholtz configuration. Exposure of
      Tradescantia (clone # 4430) inflorescences to the ELF-MF, at a flux density (B)
      corresponding to 1 mT, for 1, 6, and 24 h resulted in a time-dependent increase
      in MN frequency. The results indicate that a 50 Hz MF of 1 mT field strength is
      genotoxic in the Trad-MN bioassay and suggest that this assay may be suitable as
      a biomonitor for detecting the genotoxicity of ELF-MF in the field.

PMID- 16302170
TI  - Seasonal dynamics of the hepatotoxic microcystins in various organs of four
      freshwater bivalves from the large eutrophic lake Taihu of subtropical China and
      the risk to human consumption.
AB  - So far, little is known on the distribution of hepatotoxic microcystin (MC) in
      various organs of bivalves, and there is no study on MC accumulation in bivalves
      from Chinese waters. Distribution pattern and seasonal dynamics of MC-LR, -YR and
      -RR in various organs (hepatopancreas, intestine, visceral mass, gill, foot, and
      rest) of four edible freshwater mussels (Anodonta woodiana, Hyriopsis cumingii,
      Cristaria plicata, and Lamprotula leai) were studied monthly during Oct. 2003
      Sep. 2004 in Lake Taihu with toxic cyanobacterial blooms in the summer.
      Qualitative and quantitative determinations of MCs in the organs were done by LC
      MS and HPLC. The major toxins were present in the hepatopancreas (45.5-55.4%),
      followed by visceral mass with substantial amount of gonad (27.6-35.5%), whereas
      gill and foot were the least (1.8-5.1%). The maximum MC contents in the
      hepatopancreas, intestine, visceral mass, gill, foot, and rest were 38.48, 20.65,
      1.70, 0.64, 0.58, and 0.61 microg/g DW, respectively. There were rather good
      positive correlation in MC contents between intestines and hepatopancreas of the
      four bivalves (r=0.75-0.97, p<0.05). There appeared to be positive correlations
      between the maximum MC content in the hepatopancreas and the delta13C (r=0.919)
      or delta15N (r=0.878) of the foot, indicating that the different MC content in
      the hepatopancreas might be due to different food ingestion. A glutathione (GSH)
      conjugate of MC-LR was also detected in the foot sample of C. plicata. Among the
      foot samples analyzed, 54% were above the provisional WHO tolerable daily intake
      (TDI) level, and the mean daily intakes from the four bivalves were 8-23.5 times
      the TDI value when the bivalves are eaten as a whole, suggesting the high risk of
      consuming bivalves in Lake Taihu.

PMID- 16302172
TI  - Effect of a long-term fire retardant (Fire Trol 934) on the germination of nine
      Mediterranean-type shrub species.
AB  - Fire Trol 934 is a long-term fire retardant commonly used in fire prevention and
      extinction. Our objective was to determine the effect of this chemical on seed
      germination of nine plant species from Mediterranean-type shrublands, where these
      chemicals are potentially used. Seeds were exposed to five different Fire Trol
      concentrations, (0 (control) to 10%, on a log scale) and monitored in a
      germination chamber for nine weeks. Seeds from four Cistus species were subjected
      to an additional heat treatment that simulated thermal scarification caused by
      fire. Retardant exposure caused a significant decrease in total germination in
      all species, and exposure to the highest Fire Trol concentration (10%) resulted
      in complete inhibition of germination. However, the sensitivity to Fire Trol
      varied across species and this differential species sensitivity may potentially
      lead to different impacts in the soil seed banks depending on whether sites are
      burned or unburned. Exposure to Fire Trol 934 may affect recruitment of shrubland
      species particularly during dry autumns, due to limited leaching of these
      chemicals from the soil surface. Consequently, its use should be avoided in sites
      where particularly sensitive plant species are present.

PMID- 16302173
TI  - Investigation of histopathological and cytogenetic effects on Lepomis gibbosus
      (Pisces: Perciformes) in the Cine stream (Aydin/Turkey) with determination of
      water pollution.
AB  - Water quality and the distribution of some heavy metals in three different organs
      of Lepomis gibbosus from the Cine Stream were studied. Also, histopathological
      changes in gill, liver, and muscle tissue were examined at light microscopical
      level. Micronucleus (MN) formation in fish erytrocytes, as an indicator of
      chromosomal damage, has been increasingly used to detect the genotoxic potential
      of environmental contaminants. The frequency of MN was examined from samples of
      fish from the Cine Stream and a control group. MN frequency was higher in fish
      samples caught from the Cine Stream than that in the control group. The chemicals
      ammonia, nitrite, nitrate, orthophosphate, and sulphate were determined as
      parameters that possibly affect the gill, liver, and muscle morphology. Zn was
      the most accumulated metal in tissues as well as in water. Maximum metal
      accumulation occurred in both liver and gills. For histopathological
      examinations, samples of gills, liver, and muscle tissues of L. gibbosus were
      studied by using light microscopy. In this study, a significant decrease in mean
      length of primary and secondary lamellae were observed. Moreover, cellular
      proliferation developed with secondary lamellae fusion, ballooning degenerations
      or club deformation of secondary lamellae, as well as distribution of necrotic,
      hyperplastic and clavate secondary lamellae. In the liver, altered staining,
      swollen and ruptured parenchymal cells, loss of cord structure, reduce of
      glycogen in hepatocytes, and vacuolar structure filled with cellular debris and
      many dark particles were seen. In muscle tissue, focal necrosis, cellular
      dissolution, and a decline or loss of striation in muscle fibres were found.

PMID- 16302174
TI  - Variation in the response of juvenile and adult gastropods (Lymnaea stagnalis) to
      cyanobacterial toxin (microcystin-LR).
AB  - Owing to the increasing public health problem related to the proliferation of
      toxin-producing cyanobacteria in aquatic ecosystems, we have investigated the
      response of the pond snail Lymnaea stagnalis exposed to 33 microg/L microcystin
      LR for 6 weeks, through its life traits (survival, growth, fecundity) and
      locomotion; uptake of microcystin-LR was also quantified in the snail body
      tissues. To study the potential plasticity of the response related to the
      development stage, snails were exposed to the toxin as sexually immature and
      mature. According to our results, microcystin-LR accumulated in snail tissues at
      a higher level in juveniles (7.96 ng/g fresh weight) versus adults (2.17 ng/g
      fresh weight). Whatever the age, survival, growth, and locomotion were not
      affected by the toxin, and fecundity of polluted adults was reduced by half.
      These results are discussed in terms of negative effects of aqueous microcystin
      LR occurrence on the dynamics of natural populations of gastropods.

PMID- 16302175
TI  - Analysis of cyanobacterial-derived saxitoxins using high-performance ion exchange
      chromatography with chemical oxidation/fluorescence detection.
AB  - A single run HPLC method utilizing ion exchange as the separation mode with a
      novel mobile phase system coupled to chemical postcolumn oxidation and
      fluorescence detection has been developed and demonstrated to be applicable to
      the quantitative analysis of paralytic shellfish poisons (PSPs) produced by
      Australian cyanobacteria (Anabaena circinalis) and other cyanobacteria. Both the
      cyanobacterial matrix and natural water constituents did not significantly affect
      the performance of this method. The daily precision of this method was adequate
      for it to be considered as a routine analytical tool for direct PSP analysis
      (prePSP concentration is not required) of cyanobacterial extracts and water
      bodies containing PSPs (C1, C2, GTX2, GTX3, NEO, STX) in the low parts per
      billion concentration range (10-70 ppb).

PMID- 16302176
TI  - The role of cardiopulmonary fitness and its genetic influences on surgical
      outcomes.
AB  - BACKGROUND: Outcome after major surgery remains poor in some patients. There is
      an increasing need to identify this cohort and develop strategies to reduce
      postsurgical morbidity and mortality. Central to outcome is the ability to mount
      cardiovascular output in response to the increased oxygen demand associated with
      major surgery. METHODS: A medline search was performed using keywords to identify
      factors that affect, and genetic influences in, disease and outcome from surgery,
      and all relevant English language articles published between 1980 and 2005 were
      retrieved. Secondary references were obtained from key articles. RESULTS:
      Preoperative cardiopulmonary exercise testing assesses patient fitness,
      highlights those at particular risk and, combined with triage to critical care,
      facilitates significant improvement in surgical outcome. However, genetic factors
      also influence responses to increased oxygen demand, and some patients are
      genetically predisposed to mounting increased inflammatory responses, which raise
      oxygen demand further. Polymorphisms in genes influencing fitness (angiotensin
      converting enzyme) and immune and inflammatory responses (such as interleukin 6)
      may associate with surgical outcome. CONCLUSIONS: Development of preoperative
      screening methods like cardiopulmonary exercise testing and genotype analysis to
      identify index factors may permit better patient stratification, provide targets
      for future tailored treatments and so improve surgical outcome.

PMID- 16302177
TI  - Operability and early outcome in 100 consecutive laparotomies for peritoneal
      malignancy.
AB  - BACKGROUND: Peritoneal malignancy is common at the terminal stages of many intra
      abdominal neoplasms. In selected patients a novel approach of complete
      macroscopic tumour removal by extensive surgical cytoreduction, combined with
      intraperitoneal chemotherapy, provides a possibility of cure. Initial experience
      with 100 consecutive laparotomies is reported. METHODS: Between 1994 and 2002,
      218 patients with peritoneal malignancy were referred to a specialized unit. One
      hundred underwent laparotomy, of whom 85 had a primary appendiceal tumour.
      Treatment aims were complete macroscopic tumour excision combined with
      intraoperative intraperitoneal chemotherapy. RESULTS: Sixty-five patients had
      complete macroscopic tumour excision, 28 palliative major cytoreduction and seven
      were inoperable. The overall mortality rate was 8 per cent. The most common
      complications were pulmonary (25 per cent) and wound (14 per cent) infection. At
      a median follow-up of 30 (range 3-113) months, 44 of 51 patients with primary
      appendiceal tumours who had complete macroscopic cytoreduction were alive and 36
      were disease free. CONCLUSION: Cytoreduction combined with intraperitoneal
      chemotherapy is an emerging technique with promising results in selected patients
      with peritoneal malignancy.

PMID- 16302178
TI  - Low barrier kinetics: dependence on observables and free energy surface.
AB  - Dynamics on free energy surfaces with high activation barriers are usually
      treated by few-state kinetics models, yielding characteristic rate coefficients
      and amplitudes depending on the connectivity of the states. When the barriers are
      low (< 3 kT), the assumption of instantaneous equilibration of the transition
      state, and hence, the few-state kinetics treatment, break down. Langevin dynamics
      is used here to explore the characteristic trends that occur in such cases, as a
      function of barrier height, number of barriers, dimensionality of the free energy
      surface, and switching functions that describe how spectroscopic probes vary from
      reactant to product. The result is a systematic phenomenological description of
      low barrier kinetics and dynamics.

PMID- 16302179
TI  - Local recurrence after curative resection for rectal cancer is associated with
      anterior position of the tumour.
AB  - BACKGROUND: Mobilization of rectal cancer can be difficult if the tumour is
      located anteriorly and may result in a higher incidence of local recurrence. The
      aim of this study was to determine whether local recurrence and survival
      following curative resection of rectal cancer were associated with the position
      of the tumour. METHODS: Data were drawn from a comprehensive, prospective
      hospital registry of all resections for rectal cancer from January 1990 to
      December 1998, with follow-up to December 2003. RESULTS: The 5-year local
      recurrence rate was 15.9 (95 per cent confidence interval (c.i.) 11.0 to 22.8)
      per cent in 176 patients with tumours that had an anterior component compared
      with 5.8 (95 per cent c.i. 2.8 to 11.9) per cent in 132 patients with tumours
      without an anterior component (P = 0.009). This association persisted after
      adjustment for other factors linked to local recurrence (hazard ratio (HR) 2.4
      (95 per cent c.i. 1.1 to 5.4)). Similarly, anterior position had a significant
      negative independent association with survival (HR 1.4 (95 per cent c.i. 1.0 to
      2.00)). CONCLUSION: Anterior position is an independent negative prognostic
      factor for both local recurrence and survival after curative resection of rectal
      cancer.

PMID- 16302182
TI  - Extending mechanistic routes in heterazolium catalysis--promising concepts for
      versatile synthetic methods.

PMID- 16302183
TI  - Atmospheric aerosols: composition, transformation, climate and health effects.
AB  - Aerosols are of central importance for atmospheric chemistry and physics, the
      biosphere, climate, and public health. The airborne solid and liquid particles in
      the nanometer to micrometer size range influence the energy balance of the Earth,
      the hydrological cycle, atmospheric circulation, and the abundance of greenhouse
      and reactive trace gases. Moreover, they play important roles in the reproduction
      of biological organisms and can cause or enhance diseases. The primary parameters
      that determine the environmental and health effects of aerosol particles are
      their concentration, size, structure, and chemical composition. These parameters,
      however, are spatially and temporally highly variable. The quantification and
      identification of biological particles and carbonaceous components of fine
      particulate matter in the air (organic compounds and black or elemental carbon,
      respectively) represent demanding analytical challenges. This Review outlines the
      current state of knowledge, major open questions, and research perspectives on
      the properties and interactions of atmospheric aerosols and their effects on
      climate and human health.

PMID- 16302184
TI  - An efficient design for the rigid assembly of four bidentate chromophores in
      water-stable highly luminescent lanthanide complexes.

PMID- 16302185
TI  - Thyroid hormone stimulates gamma-glutamyl transpeptidase in the developing rat
      cerebra and in astroglial cultures.
AB  - Hypothyroidism in the developing rat brain is associated with enhanced oxidative
      stress, one of the earliest manifestations of which is a decline in the level of
      glutathione (GSH). To investigate the role of thyroid hormone (TH) on GSH
      homeostasis, the effect of TH on gamma-glutamyl transpeptidase (gammaGT), the key
      enzyme involved in the catalysis of GSH, was studied. Hypothyroidism declined the
      specific activity of cerebral gammaGT at all postnatal ages examined (postnatal
      day 1-20) with a maximum inhibition of 42% at postnatal day 10. Intraperitoneal
      injection of TH to 15-day-old rat pups increased the specific activity of gammaGT
      by 25-30% within 4-6 hr. Treatment of primary cultures of astrocytes by TH also
      enhanced the specific activity of gammaGT by 30-40% within 4-6 hr. The induction
      of gammaGT by TH was blocked by actinomycin D or cycloheximide. gammaGT is an
      ectoenzyme that is normally involved in the catabolism of GSH released by
      astrocytes. In the presence of the gammaGT-inhibitor, acivicin, GSH released in
      the culture medium of astrocytes increased linearly for at least 6 hr and TH had
      no effect on this accumulation pattern. In the absence of acivicin, GSH content
      of the medium from TH-treated cells was significantly lower than that of
      untreated controls due to activation of gammaGT by TH and a faster processing of
      GSH. Because the products of gammaGT reaction are putative precursors for
      neuronal GSH, the activation of gammaGT by TH may be conducive to GSH synthesis
      in neurons and their protection from oxidative stress.

PMID- 16302186
TI  - PDT-induced death of sensory neurons and glial cells in the isolated crayfish
      stretch receptor after proteolytic treatment.
AB  - To study the involvement of neuroglial interactions in photodynamic damage of
      crayfish stretch receptor, which consists of only two neurons surrounded by
      satellite glial cells (SGCs), we attempted to proteolytically uncouple neurons
      and glia and then compare the responses of these cells to photosensitization when
      intercellular communications were intact or impaired. After incubation of
      isolated stretch receptors with pronase or collagenase they were photosensitized
      with Photosens, a mixture of sulfonated alumophthalocyanines AlPcS(n) (n = 2, 3,
      and 4; mean n = 3.1). In the next 6 hr the preparations were double fluorochromed
      with propidium iodide and Hoechst-33342 to visualize necrotic and apoptotic
      cells. Proteolytic treatment shortened bioelectric neuron response and
      precipitated its functional inactivation; however, it did not significantly
      impair neuron morphology and did not induce its necrosis either in the darkness
      or under photosensitization. Photodynamic treatment induced necrosis of neurons
      and SGC and apoptosis of glial cells. Pronase but not collagenase increased
      percent of necrotic and apoptotic SGCs in the darkness and thus reduced the
      number of glial cells around the neuron; however, both pronase and collagenase
      prevented photodynamically induced apoptosis of glial cells. The involvement of
      neuron-to-glia signaling interactions in this phenomenon is suggested.

PMID- 16302187
TI  - Nerve growth factor increases connexin43 phosphorylation and gap junctional
      intercellular communication.
AB  - The function of gap junctions is regulated by the phosphorylation state of their
      connexin subunits. Numerous growth factors are known to regulate connexin
      phosphorylation; however, the effect of nerve growth factor on gap junction
      function is not understood. The phosphorylation of connexin subunits is a key
      event during many aspects of the lifecycle of a connexin, including open/close
      states, assembly/trafficking, and degradation, and thus affects the functionality
      of the channel. PC12 cells infected with connexin43 (Cx43) retrovirus were used
      as a neuronal model to characterize the signal transduction pathways activated by
      nerve growth factor (NGF) that potentially affect the functional state of Cx43.
      Immunoblot analysis demonstrated that Cx43 and the mitogen-activated protein
      kinase (MAPK), ERK-1/2, were phosphorylated in response to TrkA activation via
      NGF and that phosphorylation could be prevented by treatment with the MEK-1/2
      inhibitor U0126. The effects of NGF on gap junction intercellular communication
      were examined by monitoring fluorescence recovery after photobleaching PC12-Cx43
      cells preloaded with calcein. Fluorescence recovery in the photobleached area
      increased after NGF treatment and decreased when pretreated with the MEK-1/2
      inhibitor U0126. These data are the first to show a direct signaling link between
      neurotrophins and the phosphorylation of connexin proteins through the MAPK
      pathway resulting in increased gap junctional intercellular communication.
      Neurotrophic regulation of connexin activity provides a novel mechanism of
      regulating intercellular communication between neurons during nervous system
      development and repair.

PMID- 16302188
TI  - Apotransferrin and the cytoskeleton of oligodendroglial cells.
AB  - Apotransferrin (aTf), has been shown to accelerate the differentiation of
      oligodendroglial cells (OLGcs) in primary cultures and to increase the expression
      of different components of the myelin cytoskeleton (CSK). We examined the
      incorporation and distribution of human aTf (aTfh) exogenously added to OLGcs
      cultures and its effects on the CSK of the OLGcs. When OLGcs treated with aTfh
      were extracted with a CSK-stabilizing buffer containing detergent, aTfh was found
      in the soluble fraction. In vitro experiments showed that purified tubulin was
      not altered by the addition of aTfh. In OLGc primary cultures treated with aTfh,
      this glycoprotein showed a punctate distribution pattern along the OLGc
      processes. Treatment of the cultures with colchicine, cytochalasin, or taxol
      induced a displacement of the immunoreactivity of aTfh toward the OLGc soma.
      Analysis of the effects of aTfh on the cell distribution of tyrosinated and
      detyrosinated tubulin and STOP (stable tubule only polypeptide), showed that aTfh
      added to OLGc cultures promoted changes suggesting a stabilizing effect on the
      microtubules (MT) at the tip of the processes. Kinesin and dynein were found to
      colocalize with the aTfh, indicating that these motors participate in the
      transport of the added glycoprotein. Moreover, after treatment with aTfh,
      clathrin immunoreactivity was displaced from the OLGc body toward the cell
      processes. These results indicate that although aTfh added to OLGcs does not
      interact directly with CSK components, it seems to be transported in clathrin
      coated vesicles from the cell body to the tips of the OLGc processes where it
      promotes their stabilization. This mechanism may be of importance in the
      increased formation of the myelin membrane induced by aTf.

PMID- 16302189
TI  - Contact endoscopic findings in hereditary hemorrhagic telangiectasia.
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia is characterized by
      angiodysplastic lesions. So far, knowledge is limited on the vascular
      architecture and rate of occult manifestation of telangiectases. Contact
      endoscopy has not been used for this task before. METHODS: Eleven patients with
      hereditary hemorrhagic telangiectasia were examined with contact endoscopy to
      identify occult telangiectases. Sixty enoral telangiectases were studied in
      detail to characterize their architecture. RESULTS: No occult telangiectases
      could be detected. In most cases, telangiectases consisting of a simple dilated
      loop were small. In contrast, most of the complex telangiectases were larger.
      CONCLUSIONS: Visually normal areas in patients with hereditary hemorrhagic
      telangiectasia did not seem to have abnormal vascularization. Simple dilated
      capillary loops might be precursors of telangiectases with a more complex
      structure. Contact endoscopy seems to be a promising tool for the in vivo
      monitoring of therapies and the natural course of vascular disorders in humans
      and in animal models.

PMID- 16302190
TI  - Deep plane cervicofacial flap: a useful and versatile technique in head and neck
      surgery.
AB  - BACKGROUND: Large oncosurgical defects of the cheek present a challenging
      reconstructive problem, especially when skin resections are combined with other
      procedures such as parotidectomy and/or neck dissection. METHODS: We present our
      experience with the deep plane cervicofacial flap (DPCFF) for reconstructing zone
      1 (n=7), zone 2 (n=6), and zone 3 (n=5) cheek defects resulting from excision of
      primary cutaneous malignancies (n=13) and metastatic parotid (n=6) and/or neck
      (n=4) disease with skin involvement. The patients were between 65 and 88 years of
      age (mean, 76.7 years). The design of the flap was determined by the location of
      the defect and the need for simultaneous parotidectomy and/or neck dissection.
      Sixteen flaps were anteriorly based, whereas two were posteriorly based. RESULTS:
      Twelve patients underwent simultaneous parotidectomy (n=11) and/or neck
      dissection (n=10) and/or facial reanimation procedures (n=6). The size of the
      cutaneous defects ranged from 4 x 4 to 10 x 10 (mean, 5.6 x 5.3) cm. Eight
      patients received postoperative adjuvant radiotherapy to the primary site and/or
      parotid bed and neck. Superficial marginal flap necrosis occurred in one of the
      three patients who received definitive radiotherapy before salvage surgery and
      repair with DPCFF. Other complications included one hematoma, one ectropion, and
      one retraction of the lower eyelid. Apart from mild facial contour deficiency in
      two patients, excellent functional and cosmetic outcome with good skin color and
      texture match were achieved in all patients. CONCLUSIONS: The DPCFF is a
      versatile reconstructive technique in head and neck surgery. It provides a simple
      solution for a variety of cheek defects as an excellent alternative to regional
      or free tissue transfer. It can be used when simultaneous parotidectomy and/or
      neck dissection and/or facial reanimation procedures are required. This composite
      musculo-fascio-cutaneous unit is reliable with excellent vascularity, because it
      has an axial blood supply. Division of the facial suspensory ligaments during
      elevation of the flap in the sub-superficial musculo-aponeurotic system (SMAS)
      plane increases the mobility of this flap, which facilitates transfer.

PMID- 16302191
TI  - Association between high collagenase-3 expression levels and poor prognosis in
      patients with head and neck cancer.
AB  - BACKGROUND: Squamous cell carcinoma of the head and neck (HNSCC) is a common
      cancer type. The ability for curative treatment with surgery and radiotherapy
      (RT) is usually highly dependent on tumor stage at the time of diagnosis.
      METHODS: The purpose of this study was to determine whether the expression of a
      cancer-specific proteinase, collagenase-3 (matrix metalloproteinase-13 [MMP-13]),
      is associated with survival parameters in patients with HNSCC. We studied MMP-13
      expression in tumors of 81 patients with stage I-IV HNSCC treated with surgery
      alone or in combination with radiotherapy. RESULTS: We found a subgroup of
      patients with high MMP-13 expression level in their tumors (>/=90% MMP-13
      positive tumor cells) associated with unfavorable prognosis (median overall
      survival [OS], 11.8 vs 19.6 months, p = .032). In addition, the median disease
      specific survival (DSS) time was markedly reduced in this subgroup (13.8 months
      vs 40.7 months, p = .062). When the subgroup of patients treated with a curative
      intent was studied, the same association was found in OS (13.8 vs 24.6 months, p
      = .023) and DSS (p = .004). In addition, there was a trend for association
      between >/=90% MMP-13 positivity and a recurrent tumor (p = .078) in curatively
      treated patients. CONCLUSIONS: The short survival time associated with high MMP
      13 expression levels could not be predicted by tumor size or local lymph node
      invasion. These results show that a high MMP-13 expression level is associated
      with aggressiveness of HNSCC and may have prognostic value in patient evaluation.

PMID- 16302192
TI  - Functional outcomes after laryngopharyngectomy with anterolateral thigh flap
      reconstruction.
AB  - BACKGROUND: We examined speech and swallowing outcomes and complications in
      patients with anterolateral thigh (ALT) flap reconstruction of cervical
      esophageal defects. METHODS: We retrospectively reviewed 29 patients treated with
      laryngopharyngectomy and ALT flap reconstruction at The University of Texas M. D.
      Anderson Cancer Center from March 2002 to July 2004. We compared complication
      rates, nutritional intake, number of tracheoesophageal punctures (TEPs), speech
      fluency and use, operative defects, and radiotherapy effects. RESULTS: Twenty-two
      patients had circumferential defects, and seven had partial defects. Twenty-four
      patients had radiotherapy. Eleven patients underwent TEP. Higher complication
      rates in patients after TEP compared with those without TEP were not
      statistically significant (p = .268). Ninety percent of patients with TEP spoke
      fluently. Ninety percent of all patients returned to oral alimentation without
      significant effect from TEP (p = 1.00), complications (p = 1.00), radiation
      therapy (p = 1.00), or surgical defect (p = .56). CONCLUSIONS: The ALT flap
      successfully reconstructs laryngopharyngeal defects with excellent speech and
      swallowing results.

PMID- 16302194
TI  - Meta-analysis of glutathione S-transferase M1 genotype and risk toward head and
      neck cancer.
AB  - BACKGROUND: We sought to evaluate the estimated risk of GSTM1 null genotype and
      squamous cell carcinoma of the head and neck (SCCHN). METHODS: The studies done
      so far for GSTM1 null genotype as a risk factor associated with head and neck
      cancer are not conclusive and have shown conflicting results. A meta-analysis has
      been carried out on 22 case-control studies collected from the literature.
      Precision of the risk estimate and presence of publication bias in those studies
      are also evaluated by funnel plot analysis. RESULTS: A total of 3527 cases and
      4211 controls constitute the subjects of meta-analysis. The principal outcome
      measured was the odds ratio (OR) for the risk of head and neck cancer. Pooling
      the studies together, the OR was 1.50 (95% confidence interval [CI], 1.21-1.87).
      When stratified according to Asians and Caucasians, the OR increased in the
      Asians (OR, 1.93; 95% CI, 1.29-2.90), suggesting that the risk is more pronounced
      in Asians. However, a substantial amount of publication bias is also associated
      with studies conducted on the Asian population. CONCLUSION: A review of the 22
      case-control studies for risk of SCCHN and GSTM1 null genotype indicate that
      greater attention should be paid to designing future studies so that a more
      precise risk estimate can be achieved.

PMID- 16302193
TI  - Site of disease and treatment protocol as correlates of swallowing function in
      patients with head and neck cancer treated with chemoradiation.
AB  - BACKGROUND: The relationship between type of chemoradiation treatment, site of
      disease, and swallowing function has not been sufficiently examined in patients
      with head and neck cancer treated primarily with chemoradiation. METHODS: Fifty
      three patients with advanced-stage head and neck cancer were evaluated before and
      3 months after chemoradiation treatment to define their swallowing disorders and
      characterize their swallowing physiology by site of lesion and chemoradiation
      protocol. One hundred forty normal subjects were also studied. RESULTS: The most
      common disorders at baseline and 3 months after treatment were reduced tongue
      base retraction, reduced tongue strength, and slowed or delayed laryngeal
      vestibule closure. Frequency of functional swallow did not differ significantly
      across disease sites after treatment, although frequency of disorders was
      different at various sites of lesion. The effects of the chemotherapy protocols
      were small. CONCLUSIONS: The site of the lesion affects the frequency of
      occurrence of specific swallow disorders, whereas chemoradiation protocols have
      minimal effect on oropharyngeal swallow function.

PMID- 16302195
TI  - p53 apoptotic response to DNA damage dependent on bcl2 but not bax in head and
      neck squamous cell carcinoma lines.
AB  - BACKGROUND: In many tumors, the p53 gene has been mutated or deleted. p53 null
      mutant mice are prone to development of a variety of neoplasms at an early age.
      In head and neck cancer, p53 mutations are detected in most cases. p53 has been
      shown to induce growth arrest, differentiation, and death when overexpressed in
      cancer cell lines. p53 responds to DNA damage by arresting the cell cycle in G1
      or G2 phase until repair can be completed. If DNA damage is severe, p53 may
      trigger programmed cell death by means of proapoptotic genes such as bax. Studies
      have suggested that p53 target genes must be intact for proper functioning of the
      tumor suppressor. METHODS: We stably expressed transcriptionally active p53 in
      head and neck squamous cell carcinoma (SCC) lines in which the endogenous gene
      was inactivated by mutation. We performed proliferation, cell death, cell cycle,
      and gene expression analysis in control clones and those treated with the DNA
      damaging agent etoposide. RESULTS: These clones proliferated slowly with
      accumulation of cells at the G1/S phase boundary but did not undergo growth
      arrest or apoptosis. Coexpression of the proapoptotic gene bax (a known target of
      p53) failed to induce apoptosis in these clones. However, p53 expression
      sensitized these cells to DNA damage-induced apoptosis by means of inhibition of
      bcl2 protein levels. CONCLUSION: We concluded that the p53 apoptotic response to
      DNA damage was dependent on bcl2 but not bax in head and neck SCC lines.

PMID- 16302196
TI  - An integrated instrumental setup for the combination of atomic force microscopy
      with optical spectroscopy.
AB  - In recent years, the study of single biomolecules using fluorescence microscopy
      and atomic force microscopy (AFM) techniques has resulted in a plethora of new
      information regarding the physics underlying these complex biological systems. It
      is especially advantageous to be able to measure the optical, topographical, and
      mechanical properties of single molecules simultaneously. Here an AFM is used
      that is especially designed for integration with an inverted optical microscope
      and that has a near-infrared light source (850 nm) to eliminate interference
      between the optical experiment and the AFM operation. The Tip Assisted Optics
      (TAO) system consists of an additional 100 x 100-microm(2) X-Y scanner for the
      sample, which can be independently and simultaneously used with the AFM scanner.
      This allows the offset to be removed between the confocal optical image obtained
      with the sample scanner and the simultaneously acquired AFM topography image. The
      tip can be positioned exactly into the optical focus while the user can still
      navigate within the AFM image for imaging or manipulation of the sample. Thus the
      tip-enhancement effect can be maximized and it becomes possible to perform single
      molecule manipulation experiments within the focus of a confocal optical image.
      Here this is applied to simultaneous measurement of single quantum dot
      fluorescence and topography with high spatial resolution.

PMID- 16302198
TI  - Phytochemical phenolics in organically grown vegetables.
AB  - Fruit and vegetable intake is inversely correlated with risks for several chronic
      diseases in humans. Phytochemicals, and in particular, phenolic compounds,
      present in plant foods may be partly responsible for these health benefits
      through a variety of mechanisms. Since environmental factors play a role in a
      plant's production of secondary metabolites, it was hypothesized that an organic
      agricultural production system would increase phenolic levels. Cultivars of leaf
      lettuce, collards, and pac choi were grown either on organically certified plots
      or on adjacent conventional plots. Nine prominent phenolic agents were quantified
      by HPLC, including phenolic acids (e. g. caffeic acid and gallic acid) and
      aglycone or glycoside flavonoids (e. g. apigenin, kaempferol, luteolin, and
      quercetin). Statistically, we did not find significant higher levels of phenolic
      agents in lettuce and collard samples grown organically. The total phenolic
      content of organic pac choi samples as measured by the Folin-Ciocalteu assay,
      however, was significantly higher than conventional samples (p < 0.01), and
      seemed to be associated with a greater attack the plants in organic plots by flea
      beetles. These results indicated that although organic production method alone
      did not enhance biosynthesis of phytochemicals in lettuce and collards, the
      organic system provided an increased opportunity for insect attack, resulting in
      a higher level of total phenolic agents in pac choi.

PMID- 16302199
TI  - Ochratoxin A induces oxidative DNA damage in liver and kidney after oral dosing
      to rats.
AB  - The nephrotoxic/carcinogenic mycotoxin ochratoxin A (OTA) occurs as a contaminant
      in food and feed and may be linked to human endemic Balkan nephropathy. The
      mechanism of OTA-derived carcinogenicity is still under debate, since reactive
      metabolites of OTA and DNA adducts have not been unambiguously identified.
      Oxidative DNA damage, however, has been observed in vitro after incubation of
      mammalian cells with OTA. In this study, we investigated whether OTA induces
      oxidative DNA damage in vivo as well. Male F344 rats were dosed with 0, 0.03,
      0.1, 0.3 mg/kg bw per day OTA for 4 wk (gavage, 7 days/wk, five animals per dose
      group). Subsequently, oxidative DNA damage was determined in liver and kidney by
      the comet assay (single cell gel electrophoresis) with/without use of the repair
      enzyme formamido-pyrimidine-DNA-glycosylase (FPG). The administration of OTA had
      no effect on basic DNA damage (determined without FPG); however, OTA-mediated
      oxidative damage was detected with FPG treatment in kidney and liver DNA of all
      dose groups. Since the doses were in a range that had caused kidney tumors in a 2
      year carcinogenicity study with rats, the oxidative DNA damage induced by OTA may
      help to explain its mechanism of carcinogenicity. For the selective induction of
      tumors in the kidney, increased oxidative stress in connection with severe
      cytotoxicity and increased cell proliferation might represent driving factors.

PMID- 16302200
TI  - Safety assessment of high pressure treated foods.

PMID- 16302203
TI  - On the accuracy of polypeptide masses measured in a linear ion trap.

PMID- 16302204
TI  - Determination of the enantiomer fraction of PBB 149 by gas
      chromatography/electron capture negative ionization tandem mass spectrometry in
      the selected reaction monitoring mode.
AB  - Enantioselective determination of the atropisomers of 2,2',3,4',5',6
      hexabromobiphenyl (PBB 149) in a purified sample from a bird egg was attempted in
      this work. By application of the classic method for PBB determination, i.e. gas
      chromatography coupled to electron capture negative ionization mass spectrometry
      (GC/ECNI-MS) using the bromide ions, the enantiomers interfered with another
      brominated compound. Subsequent measurements clarified that this interference did
      not occur in the mass chromatogram of the molecular ion of PBB 149. Therefore, a
      GC/ECNI tandem mass spectrometry (MS/MS) method was developed, based on the
      fragmentation of [M]-. A suitable precursor-product ion transition was found for
      m/z 627.5 --> 80 +/- 1.5, representing the most abundant ion trace of the
      molecular ion and the bromide ions. Optimization of the ion source temperature,
      the methane gas pressure, and the collision voltages resulted in a robust method
      that could solve the problem. Subsequent injections of a technical PBB product
      (Firemaster BP-6) resulted in the anticipated racemic proportion (enantiomer
      fraction (EF) = 0.50 +/- 0.02 (n = 8)). By contrast, the EF in the purified
      extract of a bird egg was found to be 0.42 +/- 0.02 (n = 10), indicative of a
      significant enantioenrichment of the second eluting atropisomer. Additional
      measurements were performed on a non-chiral column. These measurements allowed
      for the detection of 16 hexabromobiphenyls (hexa-BBs) in Firemaster BP-6. These
      comparisons verified that PBB 149 enantiomers did not interfere with an isomer
      that could falsify the enantiomer fraction in the sample. The novel method using
      GC/ECNI-MS/MS in the selected reaction monitoring (SRM) mode was eight times more
      sensitive than application of conventional GC/ECNI-MS selected ion monitoring
      (SIM) analysis of the molecular ion.

PMID- 16302205
TI  - Performance characteristics of cholesterol oxidase for kinetic determination of
      total cholesterol.
AB  - The enzymatic method for cholesterol determination can use either an endpoint or
      a kinetic method. Not much is known concerning the properties (K(m) and V(max))
      of the commercial enzyme for the kinetic method. We measured the K(m) and V(max)
      of Brevibacterium, Streptomyces, Pseudomonas fluorescens, and Cellulomonas
      cholesterol oxidase. Brevibacterium gave the highest K(m) value (230.3 x 10(-4)
      M), followed by Streptomyces (2.17 x 10(-4) M), Cellulomonas (0.84 x 10(-4) M),
      and Pseudomonas (0.61 x 10(-4) M). The K(m) values and the linearity obtained
      from Streptomyces (2.6 mmol/L), Pseudomonas (2.1 mmol/L), or Cellulomonas (2.1
      mmol/L) were too low. Dichlorophenol isomers, acting as inhibitors, increased the
      enzyme's K(m). The addition of 3,4-dichlorophenol raised the K(m) of Streptomyces
      from 2.17 x 10(-4) to 24.89 x 10(-4) M. The linearity was increased from 2.6 to
      13.0 mmol/L. The high K(m) of Brevibacterium resulted in an insensitive reaction
      and low cholesterol linearity (7.8 mmol/L). An increase in the sample-to-reagent
      ratio from 1:100 to 1:10 enhanced the reaction rate and the linearity from 7.8 to
      20.7 mmol/L. We suggest that Brevibacterium and Streptomyces cholesterol oxidase
      (with the addition of 3,4 dichlorophenol) are good sources for serum cholesterol
      determination by the kinetic method.

PMID- 16302206
TI  - Influence of pigments and pH of urine on the determination of N-acetyl-beta-D
      glucosaminidase activity with 2-methoxy-4-(2'-nitrovinyl)-phenyl-N-acetyl-beta-D
      glucosaminide.
AB  - The influence of urinary pigments and urine pH on the spectrophotometric
      determination of N-acetyl-beta-D-glucosaminidase (NAG; EC 3.2.1.30) activity with
      2-methoxy-4-(2'-nitrovinyl)-phenyl-N-acetyl-beta-D-glucosaminide as a substrate
      was studied. The investigation was performed with human and rabbit urine samples.
      It was found that alkaline urine pH values influenced NAG activity in two ways:
      1) NAG activity decreased due to enzyme instability with pH increase, and 2) NAG
      activity increased because of the contribution of urinary pigments to absorbance
      of 2-methoxy-4-(2'-nitrovinyl)-phenol (MNP) at 505 nm. It was shown that besides
      the maximum (I) in the range of 350-360 nm of the absorption spectra of alkaline
      urine, there was a maximum (II) in the range of 380-460 nm. With the increase of
      pH, maximum II was shifted toward higher wavelengths and contributed to MNP
      absorption (5-90%). On the other hand, the maximum of MNP absorption was shifted
      toward lower wavelengths (495-400 nm) with increasing pH. Two procedures to
      eliminate the influence of urinary pigments are presented. The justification of
      applying a correction to the values of NAG activity in human and rabbit urine (a
      model system for studying the toxic effects of cadmium) was discussed.

PMID- 16302207
TI  - Lack of association between cardiac troponin T and D-dimer in the evaluation of
      myocardial damage.
AB  - Acute myocardial infarction (AMI) disrupts cardiac cell membranes, releasing
      intracellular cardiac proteins into the vascular system. Some of these proteins,
      including the cardiac troponin subunits T and I, have proven useful for
      diagnosing myocardial damage. Intracoronary thrombosis plays a key role in the
      pathogenesis of AMI, and the formation of an occlusive thrombus usually precedes
      the development of myocardial damage. To evaluate whether there is an association
      between the size of intracoronary thrombosis and myocardial damage, we analyzed D
      dimer and cTnT levels in blood samples from patients suspected to have myocardial
      damage. We investigated 102 patients who were admitted to emergency service for
      suspected myocardial damage. D-dimer was assessed with the use of the immunoassay
      Liatest D-dimer, and cTnT levels were measured with an electrochemiluminescence
      immunoassay (Troponin T STAT). D-dimer levels were lower in patients with cTnT <
      0.01 than in patients presenting cTnT > 0.01 ng/mL. We investigated the
      relationship between D-dimer and cTnT levels in the patients with cTnT > 0.01
      ng/mL (0.40 +/- 0.10 ng/mL), and no significant agreement (r = 0.20, P > 0.05)
      was observed. The levels of D-dimer were not associated with the levels of cTnT
      in patients with cTnT > 0.01 ng/mL.

PMID- 16302208
TI  - Modified salting-out method: high-yield, high-quality genomic DNA extraction from
      whole blood using laundry detergent.
AB  - Different approaches have been used to extract DNA from whole blood. In most of
      these methods enzymes (such as proteinase K and RNAse A) or toxic organic
      solvents (such as phenol or guanidine isothiocyanate) are used. Since these
      enzymes are expensive, and most of the materials that are used routinely are
      toxic, it is desirable to apply an efficient DNA extraction procedure that does
      not require the use of such materials. In this study, genomic DNA was extracted
      by the salting-out method, but instead of using an analytical-grade enzyme and
      chemical detergents, as normally used for DNA isolation, a common laundry powder
      was used. Different concentrations of the powder were tested, and proteins were
      precipitated by NaCl-saturated distilled water. Finally, DNA precipitation was
      performed with the use of 96% ethanol. From the results, we conclude that the
      optimum concentration of laundry powder for the highest yield and purity of
      isolated DNA is 30 mg/mL. The procedure was optimized, and a final protocol is
      suggested. Following the same protocol, DNA was extracted from 100 blood samples,
      and their amounts were found to be >50 microg/mL of whole blood. The integrity of
      the DNA fragments was confirmed by agarose gel electrophoresis. Furthermore, the
      extracted DNA was used as a template for PCR reaction. The results obtained from
      PCR showed that the final solutions of extracted DNA did not contain any
      inhibitory material for the enzyme used in the PCR reaction, and indicated that
      the isolated DNA was of good quality. These results show that this method is
      simple, fast, safe, and cost-effective, and can be used in medical laboratories
      and research centers.

PMID- 16302209
TI  - Endothelial NOS G894 T and MMP-3 5A/6A gene polymorphisms and hypertension in
      Serbian population.
AB  - The incidence of hypertension is increasing and it is more common in man than in
      women. Up to date, MMP-3 5A/6A polymorphism has been associated with artery
      stiffening and elevated blood pressure, whereas results considering association
      of endothelial NOS (eNOS) G894 T polymorphism with hypertension are
      controversial. The aim of our study was to analyze the possible association of
      eNOS G894 T and MMP-3 5A/6A gene polymorphisms with hypertension in Serbian
      population. Study sample consisted of 172 hypertensive and 200 normotensive
      subjects divided by gender. Both female and male group was truncated according to
      age. All subjects were genotyped for MMP-3 5A/6A and eNOS G894 T polymorphism.
      There was a significantly higher (P < 0.05) prevalence of 5A/5A genotype in
      hypertensive females compared to normotensive ones (19.30 % vs. 10.84%) even more
      pronounced in group > or =50 years, according to its recessive effect. In young
      males (<40 years), we found 3.7-fold increased risk for hypertension associated
      with allele 6A (P < 0.01), and 8.1-fold with genotype 6A/6A (P = 0.01) according
      to recessive model. We found no association of eNOS G894 T polymorphism with
      hypertension. These results indicate that there were gender- and age-specific
      differences in association of MMP-3 5A/6A polymorphism with hypertension in
      Serbian population.

PMID- 16302210
TI  - Urinary protein analysis in pre- and postoperative cancer patients.
AB  - Urinary proteins from six patients with esophageal cancer and two with stomach
      cancer were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE). Analyses were performed on days-1 to 3, 5, 7, 10, 14, and 21 (or 22)
      after surgery. The protein patterns were scanned by densitometry and divided into
      nine fractions. The main proteins in the fractions (Fr.) were identified as
      follows: immunoglobulin G in Fr. A, Tamm-Horsfall glycoprotein (THP) in Fr. B,
      transferrin in Fr. C, albumin in Fr. D, alpha(1)-acid glycoprotein in Fr. E,
      alpha(1)-microglobulin in Fr. F, retinol binding protein in Fr. G, and beta(2)
      microglobulin in Fr. I. The protein in Fr. H was not identified. The percentage
      of each fraction was calculated from the densitometry pattern of each lane. The
      percentage values were averaged among all the patients, and pre- and
      postoperative data were compared. The percentage of Frs. E, F, and G increased on
      days 1-7, and the changes in these three proteins were similar to changes in
      serum C-reactive protein (CRP). In particular, the percentage of Fr. G peaked
      within 1 day of operation, which was faster than for CRP. Conversely, other
      fractions decreased. These results suggest that urinary protein analysis is
      useful for monitoring the response to surgical stress.

PMID- 16302211
TI  - Association of the -183 polymorphism in the IFN-gamma gene promoter with
      hepatitis B virus infection in the Chinese population.
AB  - Interferon-gamma (IFN-gamma) is a pleiotropic cytokine that plays an important
      role in regulating cellular immune responses. Regulation of IFN-gamma expression
      is considered to be strictly controlled at the transcriptional level. Two single
      nucleotide polymorphisms (SNPs) within the human IFN-gamma promoter (at positions
      -183 and -155) are considered to influence the promoter activity by altering the
      acting transcription factor-1 (AP-1) binding. We sought to assess the association
      between the SNPs of the IFN-gamma promoter and the host susceptibility to
      hepatitis B virus (HBV) infection, as well as its interaction with age and
      gender. No polymorphism at position-155 was detected in any of the participants,
      but a significant difference was found in the polymorphism at position -183
      between the cases and controls (G/T and T/T vs. GG; P < 0.01, odds ratio (OR) =
      4.50 (95% confidence interval (CI) = 2.23-9.09). A susceptibility analysis
      revealed a gradually increased trend of the OR value from the young to the old
      group (OR = 3.03, 4.17, and 5.56). Similarly, the association of the -183
      polymorphism was markedly different in females (OR = 5.71). Our data suggest that
      the polymorphism at position -183 of the IFN-gamma gene promoter may be
      associated with susceptibility to HBV infection, and age and gender factors are
      coordinative risk factors.

PMID- 16302212
TI  - Detection of single nucleotide polymorphisms in coagulation factor XI deficient
      patients by multitemperature single-strand conformation polymorphism analysis.
AB  - Factor XI (FXI) deficiency is a rare inherited disorder which can cause bleeding
      complications especially in case of hemostatic challenge and/or in tissues with
      high fibrinolytic activity. A number of causative mutations have been described
      in FXI deficient individuals which have been detected by various screening
      methods. In this study, we present the application of the multitemperature single
      strand conformation polymorphism analysis (MSSCP) on the FXI gene, a recently
      developed methodology for the detection of single nucleotide exchanges. We
      analyzed a total of 217 polymerase chain reaction (PCR) fragments from the
      promoter region as well as from exons 1-7 and 11-15 and compared the results to
      automatic fluorescent sequencing. A total of 29 PCR fragments showed single
      nucleotide exchanges in conventional fluorescent sequencing, representing 10
      different mutations (nine missense mutations, one small deletion) and four
      frequent polymorphisms. With MSSCP electrophoresis at a standard temperature
      profile (gel temperature 35-20-10 degrees C) we were able to detect 13 of 14
      (93%) different nucleotide exchanges in 25 of 29 PCR fragments (86%). Hence, the
      detection rate for genetic variations in the FXI gene was 86%. To evaluate the
      reproducibility, MSSCP was performed twice for 174 PCR fragments and the
      consistency between two electrophoretic runs was 99%. We conclude that the MSSCP
      is a sensitive, fast, and cost effective screening method for the detection of
      FXI gene mutations.

PMID- 16302213
TI  - Evaluation of a standardized procedure for [corrected] microscopic cell counts
      [corrected] in body fluids.
AB  - A standardized urinalysis and manual microscopic cell counting system was
      evaluated for its potential to reduce intra- and interoperator variability in
      urine and cerebrospinal fluid (CSF) cell counts. Replicate aliquots of pooled
      specimens were submitted blindly to technologists who were instructed to use
      either the Kova system with the disposable Glasstic slide (Hycor Biomedical,
      Inc., Garden Grove, CA) or the standard operating procedure of the University of
      California-Irvine (UCI), which uses plain glass slides for urine sediments and
      hemacytometers for CSF. The Hycor system provides a mechanical means of obtaining
      a fixed volume of fluid in which to resuspend the sediment, and fixes the volume
      of specimen to be microscopically examined by using capillary filling of a
      chamber containing in-plane counting grids. Ninety aliquots of pooled specimens
      of each type of body fluid were used to assess the inter- and intraoperator
      reproducibility of the measurements. The variability of replicate Hycor
      measurements made on a single specimen by the same or different observers was
      compared with that predicted by a Poisson distribution. The Hycor methods
      generally resulted in test statistics that were slightly lower than those
      obtained with the laboratory standard methods, indicating a trend toward
      decreasing the effects of various sources of variability. For 15 paired aliquots
      of each body fluid, tests for systematically higher or lower measurements with
      the Hycor methods were performed using the Wilcoxon signed-rank test. Also
      examined was the average difference between the Hycor and current laboratory
      standard measurements, along with a 95% confidence interval (CI) for the true
      average difference. Without increasing labor or the requirement for attention to
      detail, the Hycor method provides slightly better interrater comparisons than the
      current method used at UCI.

PMID- 16302214
TI  - Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) treated
      with 2-chlorodeoxyadenosine.
AB  - Sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease
      (RDD) is a rare but well-defined histiocytic proliferative disorder of unknown
      etiology that usually presents with cervical lymphadenopathy, fever,
      leukocytosis, and hypergammaglobulinemia in an otherwise healthy child. Although
      many patients undergo spontaneous remission, a subset of patients with systemic
      disease has a more serious course. For those patients with a poor outcome,
      steroids and chemotherapeutic agents such as etoposide or 6-mercaptopurine plus
      low dose methotrexate have been used. We present a child with a massive cervical
      lymphadenopathy treated with 2-chlorodeoxyadenosine (2-CdA, cladribine) after
      other approaches failed.

PMID- 16302215
TI  - Response to vinorelbine and low-dose cyclophosphamide chemotherapy in two
      patients with desmoplastic small round cell tumor.
AB  - We report two cases of abdominal desmoplastic small round cell tumor (DSRCT) that
      showed a clinical response to the vinorelbine/low-dose cyclophosphamide
      combination that has been claimed to be effective for rhabdomyosarcoma. This
      observation may prompt further investigation into the activity of such a regimen
      in DSRCT patients with recurrent or refractory disease, with a view to a possible
      future role as maintenance therapy in controlling minimal residual disease in
      patients who achieve complete remission with intensive induction multimodality
      therapy.

PMID- 16302216
TI  - Autologous transplantation of CD133 selected hematopoietic progenitor cells for
      treatment of relapsed acute lymphoblastic leukemia.
AB  - A 21-year-old white male with relapsed acute lymphoblastic leukemia (ALL)
      developed an invasive Zygomycosis infection 3 weeks after beginning re-induction
      chemotherapy. Because of the high risk of fatal recurrence of the fungal
      infection, neither long-term maintenance chemotherapy nor allogeneic
      hematopoietic stem cell transplant (HSCT) was considered appropriate. Because his
      ALL blasts expressed CD34 but lacked CD133, he received a CD133 selected
      autologous graft following high-dose consolidation chemotherapy. The patient
      survives in remission 19 months after HSCT.

PMID- 16302217
TI  - Minimal residual disease (MRD) measurement as a tool to compare the efficacy of
      chemotherapeutic drug regimens using Escherichia Coli-asparaginase or Erwinia
      asparaginase in childhood acute lymphoblastic leukemia (ALL).
AB  - BACKGROUND: L-asparaginase is a crucial drug in childhood acute lymphoblastic
      leukemia (ALL) induction therapy, but much debate remains regarding the optimal
      formulation and dosage. As minimal residual disease (MRD) can accurately measure
      extremely low levels of lymphoblasts, it is a sensitive reflection of leukemia
      cell kill. We utilized MRD to compare the efficacy of Erwinia-asparaginase
      (Erwinia-asp) and E. coli-asparaginase (E. coli-asp) during induction therapy for
      childhood ALL. PROCEDURE: Of 116 precursor-B ALL patients, 22 were treated with
      Erwinia-asp, 90 with E. coli-asp, and 4 were switched from E. coli-asp to Erwinia
      asp. MRD levels at the end of induction were analyzed for 90 patients (Erwinia
      asp = 16; E. coli-asp = 74). Patients were stratified into MRD > or =10(-2),
      between 10(-2)-10(-4) and < or =10(-4). Toxicity information during induction was
      available for 110 patients. RESULTS: MRD was the only significant prognosticator
      compared to conventional criteria. Patients treated with Erwinia-asp were 6.7
      times more likely to have MRD levels > or =10(-2) (P = 0.031), reflecting slower
      lymphoblast clearance. While non-asparaginase related toxicities were similar in
      both groups, more E. coli-asp patients experienced severe asparaginase-related
      toxicity. CONCLUSION: E. coli-asp is superior to Erwinia-asp in childhood ALL
      induction. Although E. coli-asp is more toxic, this is balanced by better
      response to therapy. Early response to treatment as measured by MRD is a direct
      reflection of leukemic cell kill and is a significant prognosticator of eventual
      outcome, making it a good surrogate marker to evaluate the efficacy of induction
      drugs in childhood ALL.

PMID- 16302218
TI  - Continuous or repeated prolonged cisplatin infusions in children: a prospective
      study on ototoxicity, platinum concentrations, and standard serum parameters.
AB  - BACKGROUND: To overcome the ototoxicity of cisplatin, single bolus infusions were
      replaced by repeated prolonged infusions of lower doses or by continuous
      infusions at still lower infusion rates. However, considering ototoxicity little
      is, in fact, known about the tolerance of repeated prolonged or continuous
      infusion in children. PROCEDURE: Auditory function was monitored along with
      plasma concentrations of free and total platinum (Pt), and with standard serum
      parameters (sodium, potassium, calcium, magnesium, phosphate, chloride, and
      creatinine) in 24 children receiving cisplatin by continuous infusion for the
      treatment of neuroblastoma and osteosarcoma or by repeated 1 or 6 hr infusions
      for the treatment of germ cell tumors. RESULTS: Hearing deteriorated in 10/15
      osteosarcoma patients, 2/3 neuroblastoma patients, and 1/6 patients with germ
      cell tumors. Ototoxicity occurred after cumulative doses between 120 and 360
      mg/m(2) cisplatin. In osteosarcoma patients, ototoxicity was associated with a
      comparatively higher mean plasma concentration of free Pt. However, Pt plasma
      concentrations did not discriminate between patients with or without ototoxicity.
      In patients experiencing ototoxicity serum creatinine increased by 45% compared
      to pre-treatment levels (mean). Serum creatinine increased by 26% in patients
      without ototoxicity (P < 0.05, Mann-Whitney Rank sum test). Despite standardized
      hydration, discrete but significant changes of potassium, sodium, magnesium, and
      phosphate were observed during and/or after cisplatin infusion, which, however,
      did not discriminate between patients with and without ototoxicity. CONCLUSIONS:
      While continuous cisplatin infusions are less nephrotoxic than repeated prolonged
      infusions, we observed considerable ototoxicity in patients treated with
      continuous cisplatin infusions, which necessitates further evaluations on the
      tolerance of continuous cisplatin infusions in children.

PMID- 16302219
TI  - Comparison of conventional to intensity modulated radiation therapy for abdominal
      neuroblastoma.
AB  - OBJECTIVE: To compare three different techniques of irradiating abdominal
      neuroblastoma. PATIENTS AND METHODS: Six children with a median age of 4.1 years
      underwent radiotherapy (RT) to the primary site as part of treatment for high
      risk neuroblastoma. Four had midline disease while two had well-lateralized
      lesions. Three different RT techniques were compared. Technique A used parallel
      opposed AP/PA fields prescribed to the midplane of the patient. For Techniques B
      and C, intensity modulated radiation therapy (IMRT) plans were developed using
      inverse treatment planning with a sliding window or dynamic multileaf collimator
      approach, seven coplanar beams, and a 0.25 x 0.5 cm minimum beam resolution. The
      clinical target volume (CTV) included the tumor present prior to second look
      surgery but after induction chemotherapy with a 1.5 cm margin. The planning
      target volume (PTV) was the CTV with a 0.5 cm margin. The CTV was planned to
      receive 100% of the prescribed dose. For Technique C, the vertebral bodies
      adjacent to the tumor were included in the PTV to minimize heterogeneity of dose.
      Six MV photons were used for all techniques. Bilateral kidneys, liver, spine,
      spleen, stomach and bilateral iliac crests were contoured. RESULTS: Dose to the
      PTV and CTV were not significantly different using the three techniques. In
      comparison to Technique A, Techniques B and C delivered a lower mean dose to the
      bilateral kidneys in the four children with midline tumors but not the two
      children with a lateralized tumor where the contralateral kidney received a
      higher mean dose. Dose to the spine was less homogeneous with Technique B
      compared to Techniques A and C. The spleen, liver and stomach mean doses were
      higher using Techniques B and C compared to Technique A. CONCLUSION: Although
      Technique C was the best method of RT delivery in midline tumors with respect to
      kidney doses, this was at a cost of a higher mean dose to the liver, stomach, and
      spleen. This, together with the theoretical increase in secondary malignancies,
      should be considered when treating a child with IMRT techniques. IMRT was not
      found to be better than the conventional AP/PA field for lateralized tumors.

PMID- 16302220
TI  - Peptide fragment studies on the folding elements of dihydrofolate reductase from
      Escherichia coli.
AB  - One of the necessary conditions for a protein to be foldable is the presence of a
      complete set of "folding elements" (FEs) that are short, contiguous peptide
      segments distributed over an amino acid sequence. The FE-assembly model of
      protein folding has been proposed, in which the FEs play a role in guiding
      structure formation through FE-FE interactions early in folding. However, two
      major issues remain to be clarified regarding the roles of the FEs in determining
      protein foldability. Are the FEs AFUs that can form nativelike structures in
      isolation? Is the presence of only the FEs without mutual connections a
      sufficient condition for a protein to be foldable? Here, we address these
      questions using peptide fragments corresponding to the FEs of DHFR from
      Escherichia coli. We show by CD measurement that the FE peptides are unfolded
      under the native conditions, and some of them have the propensities toward non
      native helices. MD simulations also show the non-native helical propensities of
      the peptides, and the helix contents estimated from the simulations are well
      correlated with those estimated from the CD in TFE. Thus, the FEs of DHFR are not
      AFUs, suggesting the importance of the FEs in nonlocal interactions. We also show
      that equimolar mixtures of the FE peptides do not induce any structural
      formation. Therefore, mutual connections between the FEs, which should strengthen
      the nonlocal FE-FE interactions, are also one of the necessary conditions for a
      protein to be foldable.

PMID- 16302221
TI  - Fatal pneumonitis in children with metastatic rhabdomyosarcoma following whole
      lung radiotherapy and sequential epirubicin.
AB  - Interstitial pneumonitis is a recognized complication following whole lung
      radiotherapy. We report two cases in which fatal pneumonitis appeared to be
      precipitated by the administration of epirubicin-containing combination
      chemotherapy within 7 weeks of completion of whole lung radiotherapy. These cases
      highlight a potentially fatal interaction between radiotherapy and modern
      chemotherapy regimens.

PMID- 16302222
TI  - Diagnosis of Burkitt lymphoma in pediatric patients by thoracentesis.
AB  - The diagnosis of Burkitt lymphoma by thoracentesis has been rarely reported in
      the literature, particularly in children. From 1995 to 2004, we diagnosed six
      pediatric patients with mature B-cell neoplasms using thoracentesis as the
      initial diagnostic procedure. The cytology, immunophenotyping, and cytogenetic
      results of the pleural fluid cells were consistent with mature B-cell
      malignancies. We conclude that thoracentesis for the diagnosis of Burkitt
      lymphoma in children is safe, fast, and accurate. It should be strongly
      considered as an initial diagnostic procedure for pediatric patients with pleural
      effusions who are suspected of having B-cell malignancies.

PMID- 16302223
TI  - Numerical instabilities in the computation of pseudopotential matrix elements.
AB  - Steep high angular momentum Gaussian basis functions in the vicinity of a nucleus
      whose inner electrons are replaced by an effective core potential may lead to
      numerical instabilities when calculating matrix elements of the core potential.
      Numerical roundoff errors may be amplified to an extent that spoils any result
      obtained in such a calculation. Effective core potential matrix elements for a
      model problem are computed with high numerical accuracy using the standard
      algorithm used in quantum chemical codes and compared to results of the MOLPRO
      program. Thus, it is demonstrated how the relative and absolute errors depend an
      basis function angular momenta, basis function exponents and the distance between
      the off-center basis function and the center carrying the effective core
      potential. Then, the problem is analyzed and closed expressions are derived for
      the expected numerical error in the limit of large basis function exponents. It
      is briefly discussed how other algorithms would behave in the critical case, and
      they are found to have problems as well. The numerical stability could be
      increased a little bit if the type 1 matrix elements were computed without making
      use of a partial wave expansion.

PMID- 16302224
TI  - In vitro hemocompatibility of albumin-heparin multilayer coatings on
      polyethersulfone prepared by the layer-by-layer technique.
AB  - Polyethersulfone foils (PES)--a unique material for blood purification membranes-
      were coated with a multilayer assembly of heparin (unfractionated or high
      anticoagulant activity fraction heparin) and albumin (albumin-heparin coatings),
      or with a multilayer of albumin (albumin coating), using the layer-by-layer
      technique. The coatings combine advantages of albumin (reduction of nonspecific
      interactions) and heparin (specific interactions with blood coagulation
      proteins). The differences between the two heparins, while significant for their
      biological activity, had only a minor effect on the multilayer assembly with
      albumin monitored in situ by reflection infrared spectroscopy (FTIR MIRS).
      Uncoated as well as modified PES surfaces were evaluated using an in vitro assay
      with freshly drawn, slightly heparinized (1.5 IU heparin/mL) human whole blood.
      The blood was circulated with a roller pump over the sample surfaces in shear
      flow across rectangular slit channels ( app. 6 mL/min and 120 s(-1)) for 1.5 h at
      37 degrees C. All coatings effectively reduced platelet adhesion and activation
      according to the PF4 release. The activation of coagulation evaluated as TAT
      generation was significantly lowered for the coating composed of albumin and high
      activity heparin. A further beneficial effect of the heparin containing coatings
      was reduced complement activation as determined by different complement
      fragments.

PMID- 16302225
TI  - Development, implantation, in vivo elution, and retrieval of a biocompatible,
      sustained release subretinal drug delivery system.
AB  - A biocompatible, sustained-release subretinal drug-delivery platform was
      developed to overcome the therapeutic accessibility limitations of current
      retinal disease treatments. The prototype implants were fabricated by coating
      nitinol, poly(methyl methacrylate) or chromic gut core filaments, with a drug
      eluting polymer matrix. The polymer coatings are manufactured and coated by
      SurModics. The coating is a mixture of poly(butyl methacrylate) and poly(ethylene
      co-vinyl acetate). The drug is either triamcinolone acetonide or sirolimus. The
      rods were successfully implanted into the subretinal space of 20/24 rabbits. Four
      rabbits were lost to early surgery from a dysfunctional infusion line and
      hemorrhage. No serious complications were observed during the 4-week follow-up
      period. Slight conjunctival redness was reported in all rabbits by 1-day follow
      up, but the redness had subsided by the following week. Intraocular lens touch
      occurred in six rabbits during the implantations; of these, four had a lensectomy
      at the time of surgery, and the remaining two developed cataract. Corneal edema
      developed in three rabbits by 1-week follow-up, but subsided within 2 weeks.
      Initial observations of the implantation and elution characteristics revealed
      that the implants are well tolerated by the retinal tissue and that the implant
      can elute triamcinolone acetonide for a period of at least 4 weeks without
      eliciting an inflammatory response or complications. There were adverse clinical
      indications with the sirolimus-loaded implants at the delivered dose. Device
      retrieval required an uncomplicated surgical procedure, and revealed no
      associated or adherent tissue. Implant drug content analysis and opacity changes
      to the polymer matrix coating following retrieval demonstrated the sustained
      elution of the drug.

PMID- 16302226
TI  - Synthesis, characterization, and in vitro 5-Fu release behavior of poly(2,2
      dimethyltrimethylene carbonate)-poly(ethylene glycol)-poly(2,2
      dimethyltrimethylene carbonate) nanoparticles.
AB  - Novel ABA-type amphiphilic triblock copolymers composed of poly (ethylene glycol)
      (PEG) as hydrophilic segment and poly (2,2-dimethyltrimethylene carbonate) (PDTC)
      as hydrophobic segment were synthesized by ring-opening polymerization of 2,2
      dimethyltrimethylene carbonate (DTC) initiated by dihydroxyl PEG. The influence
      of introducing PEG block on crystalline behavior of PDTC segment was investigated
      by DSC. Polymeric micelles in aqueous medium were characterized by fluorescence
      spectroscopy and dynamic light scattering. The critical micelle concentration of
      these copolymers was in the range of 5.1-50.5 mg/L. Particle size was 80-280 nm.
      Core-shell-type nanoparticles were prepared by the dialysis technique. Zeta
      potential was measured by laser Doppler anemometry, and all nanoparticles had
      negative zeta potential. Transmission electron microscopy images demonstrated
      that these nanoparticles were spherical in shape. Anticancer drug 5-fluorouracil
      (5-Fu) as a model drug was loaded in the polymeric nanoparticles. X-ray powder
      diffraction demonstrated that 5-Fu was encapsulated into polymeric nanoparticles
      as molecular dispersion. In vitro cytotoxicity of nanoparticles was evaluated by
      MTT assay. In vitro release behavior of 5-Fu was investigated, and sustained drug
      release was achieved.

PMID- 16302227
TI  - Assuring the ethical conduct of clinical cancer trials in the developing world.

PMID- 16302228
TI  - FDG-PET in carcinoma of the uterine cervix with endometrial extension.
AB  - BACKGROUND: The authors wished to determine whether pretreatment pathologic
      evidence of endometrial invasion correlated with fluorine-18 fluorodeoxyglucose
      positron emission tomography (FDG-PET) findings and outcomes in patients with
      carcinoma of the uterine cervix. METHODS: Pretreatment whole body FDG-PET was
      performed in 58 patients with cervical carcinoma who also underwent pathologic
      evaluation of the endometrium by biopsy or dilation and curettage. FDG-PET lymph
      node status, disease free survival, and overall survival were evaluated. RESULTS:
      Thirty seven (64%) patients had pathologic evidence of endometrial invasion.
      Pelvic lymph node metastases were three times more frequent in patients with
      evidence of endometrial invasion compared with those without endometrial invasion
      (70% vs. 23%, P < 0.001). Patients with endometrial invasion also had a
      significantly increased risk of paraaortic and supraclavicular lymph node
      metastases at presentation (30% vs. 0% P = 0.006). Endometrial invasion was
      associated with a decreased 2-year disease-free survival (78% vs. 58%, P = 0.046)
      and overall survival (92% vs. 65%, P = 0.047). CONCLUSIONS: Endometrial extension
      in cervical cancer correlated strongly with risk of FDG-PET detected lymph node
      metastases in this study's population and was associated with a poor prognosis.

PMID- 16302229
TI  - Low-frequency stimulation induces a new form of LTP, metabotropic glutamate
      (mGlu5) receptor- and PKA-dependent, in the CA1 area of the rat hippocampus.
AB  - Low frequency-induced short-term synaptic plasticity was investigated in
      hippocampal slices with 60-electrode recording array. Remarkably, the application
      of low-frequency stimulation (1 Hz) for a short duration (3-5 min) resulted in
      the induction of a slow-onset long-term potentiation (LTP) in the immediate
      vicinity of the stimulated electrode. This phenomenon was observed exclusively in
      the CA1 subfield, neither in the CA3 area nor in the dentate gyrus. The induction
      of this slow-onset LTP required neither N-methyl-D-aspartate (NMDA) nor non-NMDA
      ionotropic receptor activation but was strongly dependent on metabotropic
      glutamate mGlu(5) receptor stimulation and [Ca(2+)]i increase. In addition, this
      form of synaptic plasticity was associated with an increase in cAMP concentration
      and required protein kinase A activation. Paired-pulse facilitation ratio and
      presynaptic fiber volley amplitude were unaffected when this LTP was triggered,
      suggesting the involvement of postsynaptic modifications. Although mitogen
      activated protein kinase pathway was stimulated after the application of low
      frequency, the induction and maintenance of this slow-onset LTP were not
      dependent on the activation of this intracellular pathway. The direct activation
      of adenylyl cyclase with forskolin also induced a synaptic enhancement displaying
      similar features. This new form of LTP could represent the mnesic engram of mild
      and repetitive stimulation involved in latent learning.

PMID- 16302230
TI  - Overexpression of the Del1 gene causes dendritic branching in the mouse
      mesentery.
AB  - In the present study, we established transgenic mice overexpressing Del1, a
      ligand of integrins, to examine the effect of overexpression of Del1 on vascular
      morphogenesis. In the wild-type mouse, mesenteric vessels are shaped like rakes
      consisting of a long stalk and short branches at the periphery. In contrast,
      those in transgenic mice showed typical dendritic architecture consisting of a
      few large primary branches with smaller spreading branches. The phenotype of mice
      overexpressing Del1 suggests the existence of a tissue-specific mechanism for
      branching morphogenesis in the mesentery.

PMID- 16302232
TI  - Medical student participation in surface anatomy classes.
AB  - Surface anatomy is an integral part of medical education and enables medical
      students to learn skills for future medical practice. In the past decade, there
      has been a decline in the teaching of anatomy in the medical curriculum, and this
      study seeks to assess the attitudes of medical students to participation in
      surface anatomy classes. Consequently, all first year medical students at the
      Guy's, King's and St Thomas's Medical School, London, were asked to fill in an
      anonymous questionnaire at the end of their last surface anatomy session of the
      year. A total of 290 medical students completed the questionnaires, resulting in
      an 81.6% response rate. The students had a mean age of 19.6 years (range 18-32)
      and 104 (35.9%) of them were male. Seventy-six students (26.2%) were subjects in
      surface anatomy tutorials (60.5% male). Students generally volunteered because no
      one else did. Of the volunteers, 38.2% would rather not have been subjects,
      because of embarrassment, inability to make notes, or to see clearly the material
      being taught. Female medical students from ethnic minority groups were especially
      reluctant to volunteer to be subjects. Single-sex classes improved the volunteer
      rate to some extent, but not dramatically. Students appreciate the importance of
      surface anatomy to cadaveric study and to future clinical practice. Computer
      models, lectures, and videos are complementary but cannot be a substitute for
      peer group models, artists' models being the only alternative.

PMID- 16302233
TI  - Branching patterns of the common and superficial fibular nerves in fetus.
AB  - In this study, we focused on finding out whether branching patterns of the common
      fibular (CFN) and superficial fibular (SFN) nerves change throughout the early
      period of life. The popliteal fossa and legs on both sides of 20 fetuses (13
      females and 7 males) were dissected. The ages of the fetuses varied between 20
      and 36 weeks. The levels where the CFN diverged from the sciatic nerve, the CFN
      diverged to its terminal branches, and the cutaneous branches of the SFN became
      superficial and diverged were evaluated, together with the similarity of the
      patterns of these nerves on both sides. We observed that, comparing with the
      results of previous studies on adults, both the sciatic and the CFNs in the
      fetuses were diverging into their terminal branches more distally. Additionally,
      the SFN appeared to become superficial more proximally in the fetus than in the
      adult. SFN was piercing the crural fascia before diverging into its terminal
      branches in 29 legs. Only in 8 of them, it was becoming superficial within the
      middle one-third of the leg, which was observed more frequently in males (42.9%
      of 14 legs) than in females (13.3% of 15 legs). But there was no statistically
      significant gender difference (P = 0.07). The medial dorsal cutaneous (MDCN) and
      intermediate dorsal cutaneous (IDCN) nerves which were piercing the crural fascia
      separately were observed in 27.5% of the subjects, all females. In these, MDCN
      was piercing the fascia superior to the level where the SPN becomes superficial,
      whereas the IDCN was piercing it to a level lower to this and always in the
      inferior one-third of the leg. We suggest that the detailed information about the
      branching patterns of the CPN and SPN in early ages will be beneficial,
      particularly in tumor and deformity surgery. The reason for different patterns
      and piercing levels of the nerves may be the effect of the elongating extremity
      during aging that enforces the fascia and modifies its position with a more
      stable structure, the nerve.

PMID- 16302235
TI  - Does anatomy need the Diener?

PMID- 16302236
TI  - Applications of the Colorado Visible Human Project in gastroenterology.
AB  - Several applications of the University of Colorado Visible Human project have
      recently been developed in clinical gastroenterology, including a textbook of
      endoscopic ultrasound anatomy, an internet-based journal, articles on internet
      web-sites, and simulators. Details surrounding some of these projects are
      described.

PMID- 16302237
TI  - Crystal structure of ADP/AMP complex of Escherichia coli adenylate kinase.

PMID- 16302238
TI  - A novel surgical approach to the carpal tunnel with disputed feasibility.

PMID- 16302239
TI  - Anatomical considerations of the anterior approach for central venous catheter
      placement.
AB  - Central venous catheterization (CVC) entails the catheterization of the superior
      vena cava via either the subclavian or the internal jugular vein (IJV). This
      study looked at the frequency in which a needle was inserted into the IJV using
      the anterior CVC approach, which entails inserting the needle into the apex of
      Sedillot's triangle, formed by the sternal and clavicular heads of
      sternocleidomastoid (SCM). The ipsilateral distances from the apex of Sedillot's
      triangle to the superior aspect of the sternoclavicular joint and the diameter of
      the IJV were also measured. A needle was inserted into the apex of Sedillot's
      triangle in 36 adult cadavers with mean age of 62 +/- 19 years (mean +/- SD),
      mean height of 1.6 +/- 0.18 m, and a mean weight of 55 +/- 16 kg. Subsequent
      dissections of this area revealed the relation of the needle to the IJV. Results
      indicate that on the right, the needle was inserted into the IJV in 97.14% of the
      cases. On the left, the needle entered the IJV in 78.79% of the cases. From the
      sternoclavicular joint, the apex of Sedillot's triangle was found to be 40.87 +/-
      1.62 mm and 38.73 +/- 6.34 mm on the right and left, respectively. The IJV
      diameter was 17.29 +/- 1.07 mm on the right and 15.30 +/- 0.25 mm on the left. We
      conclude that the anterior CVC approach is an anatomically accurate technique. It
      is furthermore important to realize that when performing any invasive procedure,
      a sound anatomical knowledge of the region is extremely important, as
      complications are often due to lack of understanding or misunderstanding of the
      relevant anatomy.

PMID- 16302240
TI  - Comment on ion transit pathways and gating in ClC chloride channels.

PMID- 16302241
TI  - Radial nerve contribution to brachialis in the UK Caucasian population: position
      is predictable based on surface landmarks.
AB  - The midline of the brachialis muscle is now regarded by many surgeons as an
      internervous plane, between the musculocutaneous nerve supply to the medial
      portion and a radial nerve contribution to the lateral portion, a principle
      applied in anterior approaches to the humerus. The radial nerve to brachialis has
      been described previously in East Asian specimens (Ip and Chang, 1968, Anat Rec
      162:363-371; Mahakkanukrauh and Somsarp, 2002, Clin Anat 15:206-209). We sought
      to investigate the occurrence and character of this nerve in the UK Caucasian
      population. Dissection of the musculocutaneous nerve and radial nerve was carried
      out in Caucasian cadaveric arms (n = 42). The radial nerve was dissected from the
      spiral groove to the lateral epicondyle. Where a branch to brachialis was
      encountered, its course and level of origin relative to the length of the arm
      were noted. The musculocutaneous nerve innervated the brachialis in all
      specimens. Upon investigation 67% of specimens were found to have a radial nerve
      branch to brachialis. Sixty-one percent of these branches went straight into the
      muscle, 13% descended, and 26% recurred. The level of origin of the radial nerve
      branch to brachialis was at a mean of 23% of the distance between the lateral
      epicondyle and the acromion (n = 31, range 17-37%, SD = 5.3). In three specimens,
      two branches were observed. A radial nerve contribution to the innervation of the
      brachialis was present in 67% of UK Caucasian cadavers, which is less than that
      noted by others in East Asian specimens. The level of the origin of these
      branches is predictable based on surface landmarks. This fact may be of use
      during humeral surgery.

PMID- 16302243
TI  - Vastus medialis obliquus.

PMID- 16302245
TI  - Split spinal cord malformation.
AB  - The split spinal cord is a rare congenital malformation. We report the rare
      finding of a split cord malformation in a young girl. Further evaluation of this
      anomaly revealed a Type I split cord malformation (midline bony septation), with
      no other concomitant pathological entities. Various hypotheses have been made
      regarding the embryology of this unusual form of spinal dysraphism, and these are
      reviewed along with the common clinical manifestations of this intriguing
      pathological entity.

PMID- 16302246
TI  - Attitudes of professional anatomists to curricular change.
AB  - Throughout the world, recent developments in medical curricula have led to marked
      changes in the teaching of gross anatomy. This change has involved decreasing
      curricular student contact time and the use of new methods for anatomical
      teaching. Some "modern" anatomists have welcomed the arrival of these novel
      methods while other, more "traditional," anatomists have fought to maintain the
      use of cadaveric dissection. Consequently, controversy over teaching methods has
      developed to the point that "modernist" and "traditionalist" views within the
      community of professional anatomists seem to have diverged such that the
      importance of gross anatomy in the medical curriculum is disputed and that
      cadaveric dissection by students is no longer the preferred method of teaching.
      This study tests this hypothesis using Thurstone and Chave attitude analyses to
      assess attitudes to educational change and the importance of anatomy in medicine
      and a matrix questionnaire that required professional anatomists to relate course
      aims to different teaching methods. In total, 112 completed questionnaires were
      received from anatomists who are employed at higher education institutions that
      use various teaching methods and who span the academic hierarchy. The results
      suggest that over 90% of anatomists favor educational change and approximately
      98% of professional anatomists believe that gross anatomy has an important role
      to play in clinical medicine. A clear majority of the anatomists (69%) favored
      the use of human cadaveric dissection over other teaching methods (this method
      seeming to achieve a range of different course aims/objectives) (P < 0.001;
      Kruskal-Wallis). Using Kruskal-Wallis statistical tests, the order-of-preference
      for teaching methods was found to be as follows: 1. Practical lessons using
      cadaveric dissection by students. 2. Practical lessons using prosection. 3.
      Tuition based upon living and radiological anatomy. 4. Electronic tuition using
      computer aided learning (CAL). 5. Didactic teaching alone (e.g. lectures/class
      room-based tuition). 6. Use of models. The preference for the use of human
      cadaveric dissection was evident in all groups of anatomists, whether
      "traditionalist" or "modernist" (P = 0.002, Chi-squared). These findings are
      therefore not consistent with our initial hypothesis.

PMID- 16302247
TI  - Magnetic resonance imaging study of cross-sectional area of the cervical extensor
      musculature in an asymptomatic cohort.
AB  - Magnetic Resonance Imaging (MRI) can be regarded as the gold standard for muscle
      imaging; however there is little knowledge about in vivo morphometric features of
      neck extensor muscles in healthy subjects and how muscle size alters across
      vertebral segments. It is not known how body size and activity levels may
      influence neck muscle cross-sectional area (CSA) or if the muscles differ from
      left and right. The purpose of this study was to establish relative CSA (rCSA)
      data for the cervical extensor musculature with a reliable MRI measure in
      asymptomatic females within a defined age range and to determine if side-side and
      vertebral level differences exist. MRI of the cervical spine was performed on 42
      asymptomatic female subjects within the age range of 18-45. The rCSA values for
      the cervical extensor muscles were measured from axial T1-weighted images. We
      found significant side-side rCSA differences for the rectus capitis posterior
      minor, major (P < 0.001), multifidus (P = 0.002), and the semispinalis
      cervicis/capitis (P = 0.001, P < 0.001). There were significant vertebral level
      differences in rCSA of the semispinalis cervicis/capitis, multifidus, splenius
      capitis, and upper trapezius (P < 0.001). Activity levels were shown to impact on
      the size of semispinalis cervicis (P = 0.027), semispinalis capitis (P = 0.003),
      and the splenius capitis (P = 0.004). In conclusion, measuring differences in
      neck extensor muscle rCSA with MRI in an asymptomatic population provides the
      basis for future study investigating relationships between muscular atrophy and
      symptoms in patients suffering from persistent neck pain. Clin.

PMID- 16302248
TI  - Right-sided vagus nerve stimulation inhibits induced spinal cord seizures.
AB  - We have previously shown that left-sided vagus nerve stimulation results in
      cessation of induced spinal cord seizures. To test our hypothesis that right
      sided vagus nerve stimulation will also abort seizure activity, we have initiated
      seizures in the spinal cord and then performed right-sided vagus nerve
      stimulation in an animal model. Four pigs were anesthetized and placed in the
      lateral position and a small laminectomy performed in the lumbar region. Topical
      penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord,
      was next applied to the dorsal surface of the exposed cord. With the exception of
      the control animal, once seizure activity was discernible via motor convulsion or
      increased electrical activity, the right vagus nerve previously isolated in the
      neck was stimulated. Following multiple stimulations of the vagus nerve and with
      seizure activity confirmed, the cord was transected in the midthoracic region and
      vagus nerve stimulation performed. Right-sided vagus nerve stimulation resulted
      in cessation of spinal cord seizure activity in all animals. Transection of the
      spinal cord superior to the site of seizure induction resulted in the
      ineffectiveness of vagus nerve stimulation in causing cessation of seizure
      activity in all study animals. As with left-sided vagus nerve stimulation, right
      sided vagus nerve stimulation results in cessation of induced spinal cord
      seizures. Additionally, the effects of right-sided vagus nerve stimulation on
      induced spinal cord seizures involve descending spinal pathways. These data may
      aid in the development of alternative mechanisms for electrical stimulation for
      patients with medically intractable seizures and add to our knowledge regarding
      the mechanism for seizure cessation following peripheral nerve stimulation.

PMID- 16302249
TI  - Comparison of the effectiveness of two liquid-based Papanicolaou systems in the
      handling of adverse limiting factors, such as excessive blood.
AB  - BACKGROUND: Excessive blood may compromise gynecologic Papanicolaou (Pap) smears.
      Liquid-based cytologic techniques have been developed in part to address this
      problem. In the current study, conditions of excessive blood were simulated to
      compare the ability of two liquid-based systems, ThinPrep and SurePath, to
      satisfactorily process specimens in the presence of this potentially limiting
      factor. METHODS: Equal volumes of washed epithelial cells derived from pooled
      residues of liquid Pap vials were added to a series of ThinPrep and SurePath
      vials. Increasing volumes of freshly drawn, packed erythrocytes were added to the
      vials in progressive amounts from 50 microL or 100 microL up to 3000 microL. The
      vials were processed on their respective instruments according to U.S. Food and
      Drug Administration-approved procedures for a total of six test runs. The
      cellularity of the slides was measured by averaging epithelial cell counts in a
      total of five 40x fields. RESULTS: SurePath preparations were uncompromised by
      blood until aliquots from 1000 microL to 3000 microL were reached. The ThinPrep
      system invariably was overwhelmed by the first 50-microL or 100-microL aliquot of
      blood, with epithelial cell counts dropping immediately to near zero.
      CONCLUSIONS: The cell enrichment process of the SurePath system capably handled
      significantly greater amounts of potentially obscuring blood than the membrane
      filtration method of the ThinPrep system, which was compromised by as little as
      <or= 1 drop of packed erythrocytes (1 drop = 65 microL).

PMID- 16302250
TI  - Comparison of ureteral washing and biopsy specimens in the community setting.
AB  - BACKGROUND: Ureteral lesions can be difficult to diagnose. The value of ureteral
      biopsy in addition to ureteral washings has not been defined clearly. METHODS:
      All ureteral washings and biopsies with follow-up that were performed at a single
      institution were reviewed. RESULTS: In total, 39 patients underwent ureteral
      washing, ureteral biopsy, or both and had follow-up: Eighteen patients had
      urothelial tumors at follow-up (14 high-grade carcinomas, 3 low-grade carcinomas,
      and 1 papillary urothelial neoplasm of low malignant potential). The sensitivity
      was 79% for washings and 71% for biopsies (P = 1.0), for a combined sensitivity
      of 100%. Biopsies often were scant, and cell blocks from biopsies and washings
      often were of value. CONCLUSIONS: Ureteral washings and biopsies had similar
      sensitivity and appeared to be complementary. Cell blocks often are useful for
      both specimen types.

PMID- 16302251
TI  - Rapid prescreening of Papanicolaou smears: a practical and efficient quality
      control strategy.
AB  - BACKGROUND: Efficient quality control (QC) is essential to ensure high
      sensitivity of Papanicolaou (Pap) smears. For this purpose, rescreening of 10%
      random negative smears is ineffective. Rapid rescreening (RR) of all negative Pap
      smears is more practical and has received widespread acceptance, especially in
      Europe, although its sensitivity is difficult to monitor and its retrospective
      nature may influence the vigilance of the screeners. The method of rapid
      prescreening (RPS) overcomes these drawbacks because rapid review of Pap smears
      occurs before routine full screening. METHODS: All routine conventional Pap
      smears over 2 months underwent RPS by 12 cytotechnologists. Approximately 30
      seconds were allowed to prescreen each slide. The presence of abnormal cells
      (atypical squamous cells of undetermined significance [ASCUS] or above),
      infection or endometrial cells detected on RPS was documented. All slides
      subsequently underwent routine full screening. Results of both screening methods
      were compared. RESULTS: Of a total of 8364 Pap smears, 310 (3.7%) cases were
      categorized as abnormal after final diagnosis. Of those, 135 were also detected
      on RPS (sensitivity of 43.5%). Seventeen abnormal cases were detected only on
      RPS: these consisted of 13 ASCUS cases, 3 low-grade squamous intraepithelial
      lesions, and 1 high-grade squamous intraepithelial lesion. The sensitivity of RPS
      for infections and endometrial cells was 51.6% and 28.3%, respectively.
      Implementation of RPS did not significantly impact the work flow in our
      laboratory. CONCLUSIONS: RPS is an efficient and practical QC tool. It is a
      reliable method with which to monitor sensitivity and reduce the false-negative
      rate, and because it is done before finalizing the case, it allows for timely
      corrections to the diagnosis and avoids the need to amend reports.

PMID- 16302252
TI  - Pulmonary tuberculosis in a child presenting with acute hemoptysis.
AB  - We report on a tuberculous child whose only presenting symptom was acute
      hemoptysis. His chest radiograph revealed a mass-like lesion occupying the
      posterior basal segment of the right lower lung field. Multidetector computerized
      tomography (MDCT) of the chest showed a hypodense mass supplied by the bronchial
      artery and drained by the pulmonary vein. Surgical specimens revealed caseating
      granulomatous inflammation, positive for acid-fast bacilli. The child was
      successfully treated with a short-course (6-month) regimen of antituberculous
      drugs.

PMID- 16302254
TI  - Expanded bed adsorption as a primary recovery step for the isolation of the
      insulin precursor MI3 process development and scale up.
AB  - Expanded bed adsorption (EBA) was evaluated for the isolation of the human
      insulin precursor MI3, expressed and secreted by the yeast Saccharomyces
      cerevisiae. The isoelectric point of the insulin precursor (pH 5.3) makes cation
      exchange a prime candidate for direct adsorption. In order to find a suitable
      window of operation for the process the adsorption equilibrium was analysed in a
      wide range of operating conditions (pH and conductivity) and for three different
      stationary phases. The same array of operating conditions was examined with
      regard to stable fluidisation of the adsorbents in S. cerevisiae suspensions.
      Interactions of the yeast with the fluidised stationary phase were investigated
      by a pulse response technique and the hydrodynamics of the fluidised bed under
      process conditions by residence time distribution analysis. The case study
      demonstrates that by parallel examination of product binding and fluidisation
      quality a window of operation can be found. Analysis of the binding kinetics by
      breakthrough experiments and modelling led to the definition of a set of
      operating conditions, which yield a compromise between optimal use of the
      equilibrium capacity provided by the adsorbent and high throughput required for
      an industrial separation. After initial experiments on the bench scale the
      protocol was transferred successfully to pilot scale demonstrating the design of
      a reliable operation.

PMID- 16302255
TI  - Influence of secondary reactions on the synthetic efficiency of DHAP-aldolases.
AB  - The effect of secondary reactions on DHAP-dependent aldolase stereoselective
      synthesis yields is reported. The fuculose-1-phosphate aldolase catalyzed
      synthesis between DHAP and Cbz-S-alaninal has been chosen as case study. It has
      been demonstrated that DHAP is not only chemically degraded in the reaction
      medium, but also enzymatically. The last reaction has been shown to take place
      when type II aldolases are used as biocatalysts. In order to minimize the effect
      of non-desired reactions, temperature reduction has been shown to be favorable,
      and operation at 4 degrees C has been chosen as appropriate. On the other hand,
      the fed-batch addition of DHAP also increased the synthesis yields and, combined
      with low temperature, led to almost quantitative conversion.

PMID- 16302256
TI  - Role of erythrocyte deformability during capillary wetting.
AB  - Deformability of erythrocyte was found to fundamentally alter the wetting
      dynamics of red blood cell (RBC) suspensions during their invasion into
      capillaries. Normal RBC suspensions failed to penetrate more than 1 cm into a
      glass capillary when the capillary radius was smaller than a critical value that
      is dependent on the erythrocyte concentration (about 50 microm for whole blood).
      In contrast, suspensions of rigidified RBCs, after cross-linking with different
      concentrations of glutaraldehyde or incubating with 100 ng/mL of an endotoxin,
      could penetrate any capillary larger than the erythrocyte dimension. The effect
      of RBC deformability on penetration was attributed to the enhanced shear-induced
      migration of normal deformable RBCs toward the capillary centreline, which
      imparted a higher average velocity to the RBCs than the average plasma velocity.
      As a result, the erythrocytes advanced into the capillary faster than the wetting
      meniscus, packing behind it to form a concentrated slug. This tightly packed slug
      had a high hydrodynamic resistance that could arrest the penetrating flow of
      concentrated suspensions into the small capillaries.

PMID- 16302257
TI  - Synthesis of enantiomerically pure trans-(1R,2R)- and cis-(1S,2R)-1-amino-2
      indanol by lipase and omega-transaminase.
AB  - Syntheses of trans-(1R,2R) and cis-(1S,2R)-1-amino-2-indanol (AI) were
      accomplished by a series of enantioselective enzymatic reactions using lipase and
      transaminase (TA). Lipase catalysed enantioselective hydrolysis of 2
      acetoxyindanone was employed to prepare (R)-2-hydroxy indanone (HI). trans-AI (5
      mM) (de > 98%) was produced from 20 mM (R)-2- HI using omega-TA and 50 mM (S)-1
      aminoindan as an amino donor in water-saturated ethyl acetate. For the production
      of cis-AI, the diastereomeric (2R)-AI was synthesized from (R)-2-HI using
      reductive amination, and the kinetic resolution was performed with omega-TA. The
      enantioselectivity of omega-TA for (2R)-AI was increased to 22.1 in the presence
      of 5% gamma-cyclodextrin. cis-AI (15.4 mM) (96% de) was obtained from 40 mM (2R)
      AI using 30 mM pyruvate and omega-TA (25 mg) in 10 mL of 100 mM phosphate buffer
      (pH 7.0).

PMID- 16302258
TI  - High yield production of a mutant Nippostrongylus brasiliensis
      acetylcholinesterase in Pichia pastoris and its purification.
AB  - The mutant M301A of the acetylcholinesterase B from Nippostrongylus brasiliensis
      (NbAChE) was produced in a high-cell-density fermentation of a recombinant
      methylotrophic yeast Pichia pastoris. Dissolved oxygen (DO) spikes were used as
      an indicator for feeding the carbon source. Wet cell weight (WCW) reached after 8
      days a maximum value of 316 g/L and the OD600 at this time was 280. The
      acetylcholinesterase activity increased up to 6,600 U/mL corresponding to an
      expression rate of 2 g of NbAChE per liter supernatant. The specific activity of
      the mutant NbAChE was determined after purification as 3,300 U/mg. Active site
      titration with chlorpyrifos, a strong AChE inhibitor, yielded in a specific
      activity of 3,400 U/mg. The enzyme was secreted by Pichia pastoris. Therefore, it
      could be concentrated from culture broth by cross-flow-filtration (50 kDa cut-off
      membrane). It was further purified in one-step anion-exchange chromatography,
      using a XK 50/20 column filled with 125 mL Q Sepharose HP. Mutant NbAChE was
      purified 1.9-fold up to a purity of 97% and a yield of 87%. The isolated enzyme
      was nearly homogenous, as seen on the silver stained SDS-PAGE as well as by a
      single peak after gel filtration. This extraordinary high expression rate and the
      ease of purification is an important prerequisite for their practical
      application, for example in biosensors for the detection of neurotoxic
      insecticides.

PMID- 16302259
TI  - Structured kinetic model to represent the utilization of multiple substrates in
      complex media during rifamycin B fermentation.
AB  - Industrial fermentations typically use media that are balanced with multiple
      substitutable substrates including complex carbon and nitrogen source. Yet, much
      of the modeling effort to date has mainly focused on defined media. Here, we
      present a structured model that accounts for growth and product formation
      kinetics of rifamycin B fermentation in a multi-substrate complex medium. The
      phenomenological model considers the organism to be an optimal strategist with an
      in-built mechanism that regulates the sequential and simultaneous uptake of the
      substrate combinations. This regulatory process is modeled by assuming that the
      uptake of a substrate depends on the level of a key enzyme or a set of enzymes,
      which may be inducible. Further, the fraction of flux through a given metabolic
      branch is estimated using a simple multi-variable constrained optimization. The
      model has the typical form of Monod equation with terms incorporating multiple
      limiting substrates and substrate inhibition. Several batch runs were set up with
      varying initial substrate concentrations to estimate the kinetic parameters for
      the rifamycin overproducer strain Amycolatopsis mediterranei S699. Glucose and
      ammonium sulfate (AMS) demonstrated significant substrate inhibition toward
      growth as well as product formation. The model correctly predicts the
      experimentally observed regulated simultaneous uptake of the substitutable
      substrate combinations under different fermentation conditions. The modeling
      results may have applications in the optimization and control of rifamycin B
      fermentation while the modeling strategy presented here would be applicable to
      other industrially important fermentations.

PMID- 16302260
TI  - Antitumor activity and downregulation of pro-angiogenic molecules in human
      prostate cancer cells by a novel thiazolidione compound.
AB  - BACKGROUND: Current treatments for prostate cancer are effective in many patients
      with locally advanced disease, but many of these patients eventually have
      recurrence. It is therefore important to develop alternative therapeutic agents
      with improved efficacy and tolerability. We recently identified a synthetic
      thiazolidin compound, 5-(2,4-dihydroxybenzylidene)-2-(phenylimino)-1,3
      thiazolidione (DBPT), that induces apoptosis in human colon cancer cells,
      independent of p53 and P-glycoprotein status. Here, we investigated the antitumor
      properties and mechanisms of action of this compound in human prostate cancer
      cell lines. METHODS: The effect of DBPT on cell-cycle progression and apoptosis
      in LNCaP and DU145 cells was examined by flow cytometry and Western blotting. The
      effect of DBPT on pro-angiogenic molecules was analyzed by Western blotting and
      by an enzyme-linked immunosorbent assay. RESULTS: DBPT inhibited the growth of
      LNCaP and DU145 cells with 50% inhibitory concentrations ranging from 1.6 to 5.9
      microM. Treating LNCaP and DU145 cells with DBPT led to a time-dependent cell
      cycle arrest in the G(2)/M phase and increased levels of G(2)/M checkpoint
      proteins, such as cyclin B1, cdc25C, phosphorylated histone H(3), and MPM-2. DBPT
      induced the phosphorylation of Bcl-xL and Bim, and induced apoptosis, as
      evidenced by cleavage of caspase and poly (ADP-ribose) polymerase. DBPT also
      effectively induced apoptosis in Bcl-2-overexpressing DU145 cells. Furthermore,
      DBPT decreased hypoxia-inducible factor 1 alpha and vascular endothelial growth
      factor expression in LNCaP cells under both normoxia and hypoxia. CONCLUSIONS:
      DBPT can suppress proliferation, induce apoptosis, and down regulate pro
      angiogenic molecules in prostate cancer cells, and might be useful in treating
      prostate cancer.

PMID- 16302261
TI  - Polymorphisms in genes involved in sex hormone metabolism may increase risk of
      benign prostatic hyperplasia.
AB  - BACKGROUND: This study investigates associations between polymorphisms in genes
      involved in sex hormone metabolism and measures of benign prostatic hyperplasia
      (BPH). METHODS: Community-dwelling Caucasian men (n=510, median age 60 years in
      2000) from the Olmsted County, MN, participated in a longitudinal study of BPH.
      From 1990 through 2000, urologic measures of BPH were assessed biennially from
      lower urinary tract symptom severity, peak flow rates, prostate volume, serum
      prostate specific antigen (PSA) level, acute urinary retention, and treatment for
      BPH. Men were genotyped for polymorphisms in genes involved in sex hormone
      metabolism. RESULTS: With the wildtype genotype as reference, men with HSD3B1
      (c.1100 A/C) heterozygous genotype (hazard ratio (HR)=0.7, 95% confidence
      intervals (CI)=0.6, 0.9) were at decreased risk of an enlarged prostate and men
      with CYP19 (TTTA)(n) genotype homozygous for >or=175 TTTA repeats (HR=1.5, 95%
      CI=1.1, 2.1), and CYP19 (c.1531 C/T) homozygous T variant (HR=1.6, 95% CI=1.1,
      2.2) were at increased risk of an enlarged prostate. The homozygous A variant of
      the PSA gene (g.-252 G/A), was associated with treatment for BPH (HR=2.3, 95%
      CI=1.2, 4.4). In multivariate analyses, the homozygous variant genotypes of
      AKR1C3 (c.15 G/A and c.90 G/A) were associated with a decreased risk of an
      enlarged prostate (HR=0.56, 95% CI=0.35, 0.90 and HR=0.57, 95% CI=0.33, 0.98).
      CONCLUSIONS: Polymorphisms in HSD3B1, CYP19, AKR1C3 genes may be associated with
      an enlarged prostate in older men. These data provide insights into genes that
      should be examined further for their potential role in the pathogenesis of BPH.

PMID- 16302262
TI  - Prostate cell lines secrete IL-8 in response to Mycoplasma hominis through Toll
      like receptor 2-mediated mechanism.
AB  - BACKGROUND: The roles of Toll-like receptor 2 (TLR2) and Mycoplasma in prostate
      inflammation remain unclear. We investigated whether Mycoplasma induced
      inflammatory cytokine secretion through TLR2-mediated mechanism in prostate
      cancer cell line. METHODS: Cell surface expression of TLR2 on PC-3 cells were
      examined by flowcytometry. PC-3 cells were stimulated with Mycoplasma hominis (M.
      hominis), and IL-8 secretion and NF-kappaB activation were examined. RESULTS: PC
      3 cells expressed TLR2 mRNA and cell surface TLR2 protein. The membrane fraction
      of M. hominis induced IL-8 secretion from PC-3 cells and NF-kappaB activation in
      a concentration-dependent manner. Transient transfection of the dominant negative
      mutant TLR2(P681H) into PC-3 cells attenuated M. hominis-induced IL-8 secretion
      and NF-kappaB activation. Antibody against the extracellular TLR2 domain
      significantly suppressed M. homnis-induced IL-8 secretion from the prostate cell
      lines including PC-3, PrEC, and transformed myofibroblasts. CONCLUSIONS: These
      results clearly demonstrate that the prostate cell line can secrete inflammatory
      cytokine in response to M. hominis through a TLR2-mediated mechanism.

PMID- 16302263
TI  - Protein kinase G-induced activation of K(ATP) channels reduces contractility of
      human prostate tissue.
AB  - BACKGROUND: Human cultured prostatic stromal cells respond to protein kinase G
      (PKG) activators and the nitric oxide donor, sodium nitroprusside (SNP) by
      opening ATP-sensitive potassium channels (K(ATP) channels) to reduce nifedipine
      sensitive phorbol ester-induced contractility. METHODS: PKG activators, SNP,
      diazoxide, nifedipine, isoprenaline, forskolin, and Sp-8-Br-cAMP were used to
      inhibit alpha(1)-adrenoceptor-induced contractions in tissue from transurethral
      resections of the prostate (TURP). The selective K(ATP) and large conductance
      Ca(2+) activated K(+) (BK(Ca)) channel inhibitors, glibenclamide and
      charybdotoxin, respectively were used to inhibit responses to PKG activators. RT
      PCR identified the K(ATP) channel subunits present in TURP tissue and cultured
      cells. RESULTS: The PKG activators, APT-cGMP (1 nM-100 microM) and PET-cGMP (1 nM
      100 microM), and also SNP (1 nM-100 microM), forskolin (10 microM), diazoxide
      (100 microM) and nifedipine (3 microM) inhibited phenylephrine (20 microM)
      induced contractions. The effect of APT-cGMP (1 nM-100 microM) could be reversed
      by glibenclamide, but not by charybdotoxin. TURP tissue contained mRNA for PKG
      Ialpha, Ibeta, and II and the K(ATP) channel subunits Kir6.1, Kir6.2, SUR2B, and
      SUR1. Cultured stromal cells contained only Kir6.1 and SUR2B subunit mRNA. SUR1
      mRNA was detected in one of five cultured epithelial cell lines. CONCLUSIONS: PKG
      activators reduce alpha(1)-adrenoceptor-induced contractility in TURP tissue via
      the activation of K(ATP) channels. (c) 2005 Wiley-Liss, Inc.

PMID- 16302264
TI  - Establishing normal reference ranges for PSA change with age in a population
      based study: The Krimpen study.
AB  - BACKGROUND: We aim to establish the normal pattern of prostate specific antigen
      (PSA) change with age to provide a baseline from which disease progression might
      be identified in prostate cancer patients included in active surveillance
      programs. METHODS: In a community-based study, PSA values were determined at
      baseline and after 2.1 and 4.2 years in men without prostate cancer. A bivariate
      multilevel growth curve model was used to estimate the pattern of change of PSA
      with age. RESULTS: The final model showed that PSA was related to age only. The
      future PSA of an individual can be predicted based on his age and known history
      of PSA. The model was also used to calculate PSA doubling time for men with
      different PSA values at different ages. CONCLUSIONS: This method establishes
      normal PSA levels by age using PSA history in men without prostate cancer. The
      model provides baseline data from which disease progression might be detected.

PMID- 16302265
TI  - Aberrant expression of transmembrane mucins, MUC1 and MUC4, in human prostate
      carcinomas.
AB  - BACKGROUND: Mucins are considered important markers for early diagnosis and
      targeted therapy due to their aberrant and unique expression pattern during
      malignant progression of carcinomas. Recent findings have provided substantial
      evidence for the involvement of transmembrane mucins, MUC1 and MUC4, in altered
      cell signaling, tumor growth, and metastasis. METHODS: Immunohistochemical
      analyses were performed on prostate tumor tissues for expression profiling of the
      two transmembrane mucins, MUC1 and MUC4. In cancer cell lines, the expression was
      studied by RT-PCR and immunoblot analyses. Cells were treated with DNA-methylase
      and histone-deacetylase inhibitors to examine the implication of epigenetic
      mechanism(s) in MUC4 regulation. RESULTS: The expression of MUC4 was
      significantly down regulated in prostate cancer tissues (n=38, P=0.0026) compared
      to normal/benign prostatic hyperplastic regions. A faint to moderate staining was
      observed in 26.3% cases of cancer, while 84.2% cases of adjacent normal were
      positive for MUC4 with moderate to strong staining in most cases. Similar
      observations were made in immortalized normal prostate epithelial and cancer cell
      lines. MUC1 also showed a reduced expression in prostate tumor tissues; however,
      its expression was comparable in all normal prostate epithelial and cancer cell
      lines. Interestingly, we also found that epigenetic mechanism(s) might be
      implicated in MUC4 gene silencing. CONCLUSIONS: Our data suggest that MUC4
      downregulation may be of significance for diagnostic applications in prostate
      cancer.

PMID- 16302266
TI  - Allelotyping analysis at chromosome 13q of high-grade prostatic intraepithelial
      neoplasia and clinically insignificant and significant prostate cancers.
AB  - BACKGROUND: Loss of heterozygosity (LOH) at 13q is one of the most common
      chromosomal alterations in high-stage prostate cancer, yet little is known about
      genetic changes in earlier-stage prostate cancer. METHODS: We used five
      microsatellite markers at 13q14, 21, and 33 to compare LOH frequencies in 51
      lesions of high-grade prostatic intraepithelial neoplasia (HGPIN), 21 cases of
      incidental prostate cancers (IPCs), 31 cases of latent prostate cancers (LPCs),
      and 102 cases of clinical prostate cancers (CPCs). RESULTS: The frequency of LOH
      at 13q with at least 1 marker was 0%, 38%, 56%, and 49% in HGPIN, IPCs, LPCs, and
      CPCs, respectively. No statistically significant difference was found between the
      types of prostate cancer. Allelic loss at 13q14 was significantly more frequent
      in pT4 tumors than in earlier-stage tumors (P=0.011). CONCLUSIONS: Allelic loss
      at 13q is not only an important event in the metastasis of prostate cancer, but
      also associated with the initiation of the tumor.

PMID- 16302267
TI  - A preliminary analysis and model of prostate injection distributions.
AB  - PURPOSE: Understanding the internal dynamics of prostate injections, particularly
      injection pattern distribution is a key step to developing new therapies for
      prostate disease that may be best served with a direct injection approach. Due to
      excellent properties involving liquid contrast agents, MRI can be used for
      targeting and monitoring of injections into organs and tissues. MATERIALS AND
      METHODS: Eleven intraprostatic injections were performed in vivo with canines
      using a custom transrectal guiding and imaging system for use in a standard 1.5 T
      MR scanner. In addition, 25 injections were performed on excised cadaveric human
      prostates, using a MedRad Spectris injector system. MRI was used to guide the
      injections and monitor intraparenchymal injection distribution. RESULTS: T1 and
      T2-weighted MR images were correlated with histology to produce three-dimensional
      data sets that can be used to analyze trends in injection patterns. This analysis
      was used to develop strategies for injection prediction such as gadolinium pre
      injections and diffusion-weighted imaging guidance. In addition, a rough model of
      prostate injections is described, and a preliminary injection guide is developed
      that takes into account the individual clinician's goals for therapy.
      CONCLUSIONS: MR visualization of injected therapeutic agents allows for
      prediction and monitoring of drug distributions, possibly improving efficacy and
      reducing side effects. Injection analysis and modeling may be used to assist in
      optimizing clinical treatments that require or would benefit from focal
      parenchymal injections into the prostate.

PMID- 16302268
TI  - Effects of MAP kinase inhibitors on epidermal growth factor-induced neoplastic
      transformation of human keratinocytes.
AB  - We previously reported data regarding the mechanism of neoplastic transformation
      in JB6 Cl41 mouse skin epidermal cells. However, experimental in vitro models for
      studying neoplastic transformation of human cells could provide further insight
      into the mechanisms of human cancer development. In this study, we have
      established a neoplastic transformation model with HaCaT cells, a human
      keratinocyte cell line, and showed the usefulness of this cell line for studying
      the mechanisms of neoplastic transformation. Epidermal growth factor (EGF)
      treatment induced a dose-dependent anchorage-independent cell transformation in
      HaCaT cells. Furthermore, PD98059, a mitogen-activated protein (MAP) kinase/ERK
      kinase (MEK) inhibitor, or SP600125, c-Jun N-terminal kinase (JNK) inhibitor,
      decreased cell growth, EGF-induced DNA synthesis and transformation. Unlike
      observations in the JB6 mouse epidermal cell model, SB203580, a stress-activated
      protein kinase-2/p38 alpha and beta (p38) inhibitor, increased EGF-induced
      transformation in HaCaT cells. These results suggest that extracellular-signal
      regulated kinase (ERK), JNK, or p38 are implicated in EGF-induced neoplastic
      transformation of human cells.

PMID- 16302270
TI  - Differences in muscle activation patterns during pelvic floor muscle contraction
      and Valsalva maneuver.
AB  - AIMS: To investigate the different muscle activation patterns around the abdomino
      pelvic cavity in continent women and their effect on pressure generation during a
      correct pelvic floor muscle (PFM) contraction and a Valsalva maneuver. METHODS:
      Thirteen continent women were assessed. Abdominal, chest wall, and PFM activity
      and vaginal and intra-abdominal pressure (IAP), were recorded during two tasks:
      PFM contraction and Valsalva whilst bladder base position was monitored on trans
      abdominal ultrasound. A correct PFM contraction was defined as one that resulted
      in bladder base elevation and a Valsalva resulted in bladder base depression.
      RESULTS: Comparison of the mean of the normalized EMG activity of all the
      individual muscle groups was significantly different between PFM contraction and
      Valsalva (P = 0.04). During a correct PFM contraction, the PFM were more active
      than during Valsalva (P = 0.001). During Valsalva, all the abdominal muscles (IO
      (P = 0.006), EO (P < 0.001), RA (P = 0.011)), and the chest wall (P < 0.001) were
      more active than during PFM contraction. The change in IAP was greater during
      Valsalva (P = 0.001) but there was no difference in the change in vaginal
      pressure between PFM contraction and Valsalva (P = 0.971). CONCLUSIONS: This
      study demonstrates a difference in muscle activation patterns between a correct
      PFM contraction and Valsalva maneuver. It is important to include assessment of
      the abdominal wall, chest wall, and respiration in the clinical evaluation of
      women performing PFM exercises as abdominal wall bracing combined with an
      increase in chest wall activity may cause rises in IAP and PFM descent.

PMID- 16302269
TI  - Nuclear translocation of the pro-apoptotic Bcl-2 family member Bok induces
      apoptosis.
AB  - The anti-apoptotic members of the Bcl-2 family, such as Bcl-2 and Bcl-XL, play a
      central role in preventing the induction of apoptosis via the intrinsic apoptotic
      pathway. It has been previously shown that induction of apoptosis by the pro
      apoptotic Bcl-2 family member Bok is not antagonized by either Bcl-2 or Bcl-xL,
      suggesting that Bok might have a unique role in the apoptotic cascade. We showed
      here that human Bok is the only member of the Bcl-2 family to have a leucine-rich
      sequence indicative of a nuclear export signal within its BH3 domain. Western
      blot analysis of nuclear and cytoplasmic fractions identified Bok in both the
      nucleus and the cytoplasm of HEK 293T cells, HeLa cells, and breast cancer cells,
      and its nuclear concentration increased after treatment of those cells with
      leptomycin B, an inhibitor of the exportin Crm1. Immunocytochemistry of flag
      tagged Bok confirmed its nuclear localization. Mutating the nuclear export signal
      of Bok by site-directed mutagenesis resulted in an increase in its nuclear
      localization and apoptotic activity. We also found that Crm1 interacted with wild
      type Bok but not with the mutated form. These results suggest that nuclear export
      of Bok is a regulated process mediated by Crm1, and constitutes the first report
      of a link between the apoptotic activity and nuclear localization of a pro
      apoptotic member of the Bcl-2 family.

PMID- 16302271
TI  - Pharmacokinetics, biodistribution, and antitumor efficacy of a human glandular
      kallikrein 2 (hK2)-activated thapsigargin prodrug.
AB  - BACKGROUND: Prostate cancer cells secrete unique proteases such as prostate
      specific antigen (PSA) and human glandular kallikrein 2 (hK2) that represent
      targets for the activation of prodrugs as systemic treatment of metastatic
      prostate cancer. Previously, a combinatorial peptide library was screened to
      identify a highly active peptide substrate for hK2. The peptide was coupled to an
      analog of the potent cytotoxin thapsigargin, L12ADT, to generate an hK2-activated
      prodrug that was efficiently hydrolyzed by purified hK2, stable to hydrolysis in
      human and mouse plasma in vitro and selectively toxic to hK2 producing prostate
      cancer cells in vitro. METHODS: In the current study, toxicology,
      pharmacokinetics, prodrug biodistribution, and antitumor efficacy studies were
      performed to evaluate the hK2-activated prodrug in vivo. RESULTS: The single
      intravenous maximally tolerated dose of prodrug was 6 mg/kg (i.e., 3.67
      micromole/kg) which produced peak serum concentration of approximately 36 microM
      and had a half-life of approximately 40 min. In addition, over a 24 hr period
      <0.5% of free L12ADT analog was observed in plasma. The prodrug demonstrated
      significant antitumor effect in vivo while it was being administered, but
      prolonged intravenous administration was not possible due to local toxicity to
      tail veins. Subcutaneous administration of equimolar doses produced lower plasma
      AUC compared to intravenous dosing but equivalent intratumoral levels of prodrug
      following multiple doses. CONCLUSIONS: The hK2-activated prodrug was stable in
      vivo. The prodrug, however, was rapidly cleared and difficult to administer over
      prolonged dosing interval. Additional studies are underway to assess antitumor
      efficacy with prolonged administration of higher subcutaneous doses of prodrug.
      Second-generation hK2-activated thapsigargin prodrugs with increased half-lives
      and improved formulations are also under development.

PMID- 16302272
TI  - The androgen receptor pathway is by-passed in prostate cancer cells generated
      after prolonged treatment with bicalutamide.
AB  - BACKGROUND: Experimental work in various prostate cancer models revealed that the
      androgen receptor is frequently upregulated and implicated in tumor progression.
      However, little attention has been paid to the androgen receptor-signaling
      pathway in the development of therapy resistance in patients who receive chronic
      treatment with a non-steroidal anti-androgen. METHODS: We have generated a novel
      subline, LNCaP-Bic, after prolonged treatment with androgen and bicalutamide in
      vitro. Proliferation of LNCaP-Bic cells in the absence or presence of androgen,
      tocopherol succinate, and/or bicalutamide was assessed by cell counting. Androgen
      receptor expression was determined by Western blot. Luciferase activity was
      measured in cells transfected with an androgen-responsive reporter. RESULTS: In
      basal conditions, proliferation of LNCaP-Bic cells increased more than threefold
      over that of control LNCaP cells. Neither synthetic androgen R1881 nor
      bicalutamide showed any effect on LNCaP-Bic growth in vitro. Androgen receptor
      expression did not differ between the cell subline generated in the presence of
      bicalutamide and parental LNCaP cells. The ability of R1881 to induce reporter
      gene activity in LNCaP-Bic cells was reduced by 56%. Tocopherol succinate caused
      inhibition of proliferation only in the parental cell line although the androgen
      receptor and prostate-specific antigen were down regulated by the vitamin E
      derivative in both parental LNCaP and LNCaP-Bic cells. CONCLUSIONS: Androgen
      receptor-mediated signal transaction is not enhanced in cells selected in the
      presence of bicalutamide. Our data may suggest that a more differentiated
      approach in targeting the androgen receptor is needed in prostate cancers that
      become resistant to classic endocrine treatment.

PMID- 16302273
TI  - Comparison of the growth-promoting effects of testosterone and 7-alpha-methyl-19
      nor-testosterone (MENT) on the prostate and levator ani muscle of LPB-tag
      transgenic mice.
AB  - BACKGROUND: 7-alpha-methyl-19-nortestosterone (MENT) is being considered for
      androgen replacement in testosterone deficient men and as a male contraceptive.
      Because androgenic effects on the prostate are a major concern, we have evaluated
      MENT in a transgenic model of prostate cancer. METHODS: LPB-Tag mice were
      castrated and infused with testosterone (T; 5 or 30 microg/day) or MENT (5 or 30
      microg/day) for 4 weeks. Prostate, seminal vesicle, and levator ani muscle (LAM)
      weights were compared. RESULTS: At an equivalent dose, MENT maintained or
      stimulated the mean weights of these organs more than T. However, the
      dorsolateral prostate/LAM ratio of weights did not favor MENT, but DNA/mg tissue
      and Ki 67 immunostaining suggested that MENT may increase DNA less than T.
      CONCLUSIONS: MENT is more potent than T in maintaining or stimulating prostate,
      seminal vesicle, and LAM. Using doses that resulted in comparable stimulation of
      the levator ani muscle, MENT had similar effect on prostate weight, but increased
      DNA/mg prostate less than T in this transgenic mouse model of prostate cancer.

PMID- 16302274
TI  - Proteomic analysis of fibrillin-rich microfibrils.
AB  - MS has been used to investigate the composition of fibrillin-rich microfibrils
      from non-elastic and elastic tissues, and to compare fibrillin-1 tryptic
      fingerprints derived from whole zonules, microfibrils and recombinant fibrillin
      1. In all microfibril preparations, fibrillin-1 was abundant and the only
      fibrillin isoform. MAGP-1 was the only other microfibril-associated molecule.
      gamma-Crystallin co-purified with zonular microfibrils, so this association may
      contribute to ciliary zonule anchorage to lens. Recombinant fibrillin-1 tryptic
      peptides mapped throughout the molecule and included virtually all predicted
      peptides except for those larger than 4.5 kDa, smaller than 600 Da or post
      translationally modified. In contrast, fewer microfibril tryptic fibrillin-1
      peptides were detected, although they were derived from domains throughout the
      molecule and included two peptides after the C-terminal furin processing site.
      Several microfibril-derived N- and C-terminal domains never yielded any peptides,
      while tryptic peptides from other domains yielded numerous peptides, suggesting
      that some tissue microfibril features are retained after trypsinisation. This
      first MS analysis of a purified extracellular matrix assembly has provided new
      insights into microfibril composition and fibrillin-1 organisation within them.

PMID- 16302275
TI  - Low temperature-induced systems failure in Escherichia coli: insights from rescue
      by cold-adapted chaperones.
AB  - The growth of Escherichia coli cells is impaired at temperatures below 21 degrees
      C and stops at 7.5 degrees C; however, growth of a transgenic strain producing
      the cold-adapted chaperones Cpn60 and Cpn10 from the psychrophilic bacterium
      Oleispira antarctica is good at low temperatures. The E. coli cpn(+) transgene
      offers a novel opportunity for examining the essential protein for cell viability
      at low temperatures. By screening a large-scale protein map (proteome) of cells
      of K-12 and its Cpn(+) transgene incubated at 4 degrees C, we identified 22
      housekeeping proteins involved in systems failure of E. coli when confronted with
      low temperature. Through co-immunoprecipitation of Cpn60, Northern blot, and in
      vitro refolding, we systematically identified that protein-chaperone interactions
      are key determinants of their protein functions at low temperatures. Furthermore,
      chromosomal gene deletion experiments suggest that the mechanism of cold-induced
      systems failure in E. coli is cold-induced inactivation of the GroELS chaperonins
      and the resulting failure to refold cold-inactivated Dps, ClpB, DnaK and RpsB
      proteins. These findings: (1) indicate the potential importance of chaperones in
      cold sensitivity, cold adaptation and cold tolerance in cellular systems, and (2)
      suggest the identity of a few key cold-sensitive chaperone-interacting proteins
      that get inactivated and ultimately cause systems failure in E. coli cells at low
      temperatures.

PMID- 16302276
TI  - Proteomic investigation of the molecular pathophysiology of dysferlinopathy.
AB  - Mutations in dysferlin gene cause several types of muscular dystrophy in humans,
      including the limb-girdle muscular dystrophy type 2B and the distal muscular
      dystrophy of Miyoshi. The dysferlin gene product is a membrane-associated protein
      belonging to the ferlins family of proteins. The function of the dysferlin
      protein and the cause of deterioration and regression of muscle fibres in its
      absence, are incompletely known. A functional clue may be the presence of six
      hydrophilic domains, C2, that bind calcium and mediate the interaction of
      proteins with cellular membranes. Dysferlin seems to be involved in the membrane
      fusion or repair. Molecular diagnosis of dysferlinopathies is now possible and
      the types of gene alterations that have been characterized so far include
      missense mutations, deletions and insertions.

PMID- 16302278
TI  - The cytosolic, cell surface and extracellular proteomes of the biotechnologically
      important soil bacterium Corynebacterium efficiens YS-314 in comparison to those
      of Corynebacterium glutamicum ATCC 13032.
AB  - Reference maps of the cytosolic, cell surface and extracellular proteome
      fractions of the amino acid-producing soil bacterium Corynebacterium efficiens YS
      314 were established. The analysis window covers a pI range from 3 to 7 along
      with a molecular mass range from 10 to 130 kDa. After second-dimensional
      separation on SDS-PAGE and Coomassie staining, computational analysis detected
      635 protein spots in the cytosolic proteome fraction, whereas 76 and 102 spots
      were detected in the cell surface and extracellular proteomes, respectively. By
      means of MALDI-TOF-MS and tryptic peptide mass fingerprinting, 164 cytosolic
      proteins, 49 proteins of the cell surface and 89 extracellular protein spots were
      identified, representing in total 177 different proteins. Additionally, reference
      maps of the three cellular proteome fractions of the close phylogenetic relative
      Corynebacterium glutamicum ATCC 13032 were generated and used for comparative
      proteomics. Classification according to the Clusters of Orthologous Groups of
      proteins scheme and abundance analysis of the identified proteins revealed
      species-specific differences. The high abundance of molecular chaperones and
      amino acid biosynthesis enzymes in C. efficiens points to environmental
      adaptations of this recently discovered amino acid-producing bacterium.

PMID- 16302277
TI  - Visualisation and analysis of proteomic data from the procyclic form of
      Trypanosoma brucei.
AB  - We have undertaken a large scale study of the proteins expressed in the procyclic
      form of the parasite Trypanosoma brucei, which causes African sleeping sickness,
      using 2-DE and MS. The complete data set encompasses over 2000 identifications,
      of which 770 are distinct proteins. We have discovered that multiple protein
      isoforms appear to be common in T. brucei, as most proteins have been matched to
      more than one gel spot. We have developed visualisation software to investigate
      the differences between isoforms, based on the information from the results of
      database searches with MS data. We are able to highlight instances where PTMs are
      the most likely cause of variant forms. In other cases, spots that appear
      reproducibly across replicates contain fragments of proteins, arising either as
      experimental artefacts or as part of protein degradation. We are also able to
      classify clusters of gel spots into different groups based on the pattern of
      peptides that have been matched from MS data. The entire data set is stored
      within a relational database system that allows complex queries (
      http://www.gla.ac.uk/functionalgenomics). Using specific proteins as examples, we
      demonstrate how the visualisation software and the database query facilities can
      be used.

PMID- 16302279
TI  - Proteomic studies support the use of multi-product immunoassays to monitor host
      cell protein impurities.
AB  - In the biopharmaceutical industry, recombinant protein drugs are commonly
      produced in Chinese hamster ovary (CHO) cells. During the development process,
      removal of CHO cell-derived proteins from the biopharmaceutical product is
      monitored using multi-product immunoassays. Such immunoassays are developed by
      raising antibodies to a single CHO cell protein preparation. However, these
      assays are utilized to monitor CHO cell protein impurities during the recovery of
      products from different CHO cell lines. To address whether underlying differences
      between CHO cell lines result in sufficient protein expression changes to exclude
      the suitability of multi-product immunoassays, a comparative proteomics study of
      three independently generated CHO cell lines was performed. Statistical analysis
      of over 1000 proteins resolved by 2-D PAGE demonstrated that the protein
      expression profiles of three different CHO cell lines exhibit very few
      differences in protein expression. Only 11 qualitative changes in protein
      expression and 26 quantitative changes greater than two-fold were observed.
      Identification of protein spots by mass spectrometry revealed that many of the
      observed changes were due to post-translational modifications rather than
      expression of novel proteins in each cell line. These results suggest that multi
      product immunoassays are suitable for monitoring host cell proteins in
      biopharmaceuticals produced in different CHO cell lines.

PMID- 16302280
TI  - A general precursor ion-like scanning mode on quadrupole-TOF instruments
      compatible with chromatographic separation.
AB  - MS protein identification and quantitation are key proteomic techniques in
      biological research. Besides identification of proteins, MS is used increasingly
      to characterize secondary protein modifications. This often requires trimming the
      analytical strategy to a specific type of modification. Direct analysis of
      protein modifications in proteomic samples is often hampered by the limited
      dynamic range of current analytical tools. Here we present a fast, sensitive,
      multiplexed precursor ion scanning mode--implemented on a quadrupole-TOF
      instrument--that allows the specific detection of any modified peptide or
      molecule that reveals itself by a specific fragment ion or pattern of fragment
      ions within a complex proteomic sample. The high mass accuracy of the TOF mass
      spectrometer is available for the marker ion specificity and the precursor ion
      mass determination. The method is compatible with chromatographic separation.
      Fragment ions and intact molecular ions are acquired quasi-simultaneously by
      continuously switching the collision energy between elevated and low levels.
      Using this technique many secondary modifications can be analyzed in parallel;
      however, the number of peptides carrying a specific modification that can be
      analyzed successfully is limited by the chromatographic resolution or, more
      generally, by the depth of the resolved time domain.

PMID- 16302281
TI  - 2-D protein maps of rat gastrocnemius and soleus muscles: a tool for muscle
      plasticity assessment.
AB  - Functional characterization of muscle fibers relies on ATPase activity and on
      differential measurements of metabolic proteins, including mitochondrial and
      glycolytic enzymes, glucose, lactate and lactic acid transporters, calcium
      cycling proteins and components of the contractile machinery. The recent
      introduction of microarray technology has enabled detailed gene expression
      studies under different physiological and pathological conditions, thus
      generating novel hypotheses on muscle function. However, microarray approaches
      are limited by the incomplete genome coverage of currently available chips, and
      by poor correlation between mRNA concentration and protein expression level. We
      have used 2-DE and MS to build a reference map of proteins from rat mixed
      gastrocnemius and soleus muscle, and to assess qualitative and quantitative
      differences in protein distribution between these two functionally dissimilar
      muscles. More than 800 spots on each gel were detected by silver staining, of
      which 167 were excised, digested in-gel with trypsin and analyzed by ESI-MS/MS.
      One hundred and twenty eight distinct gene products were identified, including
      metabolic, transport and contractile proteins. Forty one spots displayed
      differences in relative expression level between mixed gastrocnemius and soleus
      samples. These data not only enable differentiation of functionally distinct slow
      twitch and fast-twitch fiber types, but also provide tools for investigating
      muscle plasticity in response to physiological and environmental conditions such
      as aging or hypoxia.

PMID- 16302282
TI  - A model for second-trimester Down syndrome sonographic screening based on facial
      landmarks and digit length measurement.
AB  - OBJECTIVE: To determine whether Down syndrome can be detected by combining
      measurements of fetal nasal bone (NB) length, prenasal thickness (PT) and digits
      2 and 3 of the hand. METHODS: Two hundred and fifty-four normal and 25 Down
      syndrome fetuses were scanned between 15 and 33 weeks' gestation. Physicians
      performing the scans were not blinded to the fetal karyotype. Both PT and NB were
      measured in a mid-sagittal plane. For PT measurement calipers were placed between
      the frontonasal angle and the outer skin edge. Digits 2 and 3 of one hand were
      also measured. The results (except for PT/NB ratio) were expressed in multiples
      of the normal gestation-specific median (MoM). A logistic regression model was
      used to estimate the odds of the fetus having Down syndrome given different
      combinations of NB, PT, PT/NB ratio, and digits 2 and 3 measurements. The odds
      were used to calculate the risk of Down syndrome for each pregnant woman from her
      age and measurements. RESULTS: The median PT MoM for unaffected fetuses and Down
      syndrome fetuses was 1.12 vs. 1.35 (P < 0.0001). The median NB MoM for unaffected
      and Down-syndrome fetuses was 1.03 vs. 0.81 (P < 0.001) and the PT/NB ratio MoM
      for unaffected and Down-syndrome fetuses was 0.63 vs. 0.96 (P < 0.001). The
      respective median MoM values for digits 2 and 3 of the Down-syndrome fetuses were
      significantly smaller (0.81 vs. 0.93 and 0.89 vs. 0.95, respectively, P = 0.003).
      Only the PT/NB ratio and digit 2 were finally included in the logistic regression
      equation. Using a 1 in 200 risk cut-off, the observed sensitivity and false
      positive rate were 76% and 6.7%, respectively. CONCLUSION: Combining the PT/NB
      ratio and digit 2 measurements yielded a promising screening detection rate.
      Confirmation of our findings in a prospective study is needed before the method
      can be used clinically.

PMID- 16302283
TI  - A rare abnormal karyotype (45,X/47,XY + 18) associated with increased nuchal
      translucency thickness.

PMID- 16302284
TI  - Metopic suture in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation.
AB  - OBJECTIVE: To investigate the development of the frontal bones and metopic suture
      in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation. METHODS: Three
      dimensional (3D) ultrasound was used to measure the height of and gap between the
      frontal bones in 75 fetuses with trisomy 21 and these were compared to the
      measurements in 200 normal fetuses at 11 + 0 to 13 + 6 (median, 12 + 6) weeks of
      gestation. RESULTS: In the fetuses with trisomy 21, compared to the normal
      fetuses, there was no significant difference in either the height of the frontal
      bones (mean difference 0.16 SD, range -1.78 to 2.17 SD; P = 0.369) or the gap
      between them (mean difference 0.012, 95% CI -0.073 to 0.097; P = 0.780).
      Additionally, within the group of trisomy 21 fetuses there were no significant
      differences in the development of the frontal bones and metopic suture between
      those with absent (n = 46) and those with present (n = 29) nasal bone.
      CONCLUSIONS: In trisomy 21 the development of the frontal bones and metopic
      suture is as normal and is independent from the development of the nasal bones.

PMID- 16302285
TI  - The extent of endosonographic anal sphincter defects after primary repair of
      obstetric sphincter tears increases over time and is related to anal
      incontinence.
AB  - OBJECTIVE: To describe and classify endosonographic obstetric sphincter defects
      at 1 week, 3 months and 1 year after primary repair, and to relate the
      endosonographic results to anal sphincter pressure and to symptoms of anal
      incontinence over time. METHODS: Forty-one women who had suffered a third- or
      fourth-degree perineal tear at delivery underwent anal endosonography and anal
      manometry 1 week, 3 months and 1 year after primary suture of the tear. The
      extent of the endosonographic defects was described using defect scores ranging
      from 0 (no defect) to 16 (maximal defect), the score taking into account the
      location and the longitudinal and circumferential extent of the defect. The women
      answered a questionnaire with regard to bowel function 1 and 4 years after
      delivery, the degree of incontinence being expressed as a Wexner score. RESULTS:
      Some 90% (37/41) of the women had endosonographic defects at 1 week, 3 months and
      1 year. The endosonographic defect scores increased significantly between the
      first and second examinations and then remained unchanged. At 1 year there was a
      negative correlation between endosonographic sphincter defect score and sphincter
      pressure. At 1 and 4 years, 54% (22/41) and 61% (25/41) of the women,
      respectively, had a Wexner score >/= 1. There was a positive correlation between
      the endosonographic sphincter defect score at 1 week, 3 months and 1 year and the
      Wexner incontinence score at 1 and 4 years. The endosonographic sphincter defect
      score at 1 week was the variable that was most predictive of the Wexner score at
      4 years (r = 0.48, P = 0.002). CONCLUSION: The higher the endosonographic
      sphincter defect score after primary repair of an obstetric sphincter tear the
      lower the sphincter pressure and the higher the risk of anal incontinence.

PMID- 16302286
TI  - Exercise capacity in subjects with type 1 diabetes mellitus in eu- and
      hyperglycaemia.
AB  - BACKGROUND: Circumstantial evidence suggests that an increase in plasma glucose
      availability improves exercise capacity in subjects with type 1 diabetes
      mellitus. The aim of this study was to assess exercise capacity in eu- and
      hyperglycaemic conditions in subjects with type 1 diabetes. METHODS: Eight
      moderately exercise-trained male subjects with type 1 diabetes on continuous
      subcutaneous insulin infusion were studied. Using identical insulin infusion
      rates, the patients were randomly allocated to perform two stepwise ergometer
      tests in eu- and hyperglycaemic clamp conditions. The primary endpoint was the
      peak power output; the secondary endpoints comprised the rate of perceived
      exertion, lactate levels, heart rate, and respiratory exchange ratio. RESULTS: Eu
      and hyperglycaemic clamp conditions were observed at a plasma glucose
      concentration of 5.3 +/- 0.6 mmol/L and 12.4 +/- 2.1 mmol/L, respectively (mean
      +/- SD), and remained stable throughout the physical exercise. Insulin levels
      were similar in both conditions. Hyperglycaemia did not result in a significant
      increase in the peak power output compared to euglycaemia (mean paired difference
      of 4.96 W, 95% CI - 11.3 to 21.2, p = 0.49). Hyperglycaemia did not have a
      significant impact on the secondary endpoints compared to euglycaemia.
      Sensitivity analyses confirmed these results. CONCLUSIONS: In subjects with type
      1 diabetes, exercise capacity is not influenced by hyperglycaemia. Comparable
      levels of lactate and similar respiratory exchange ratio suggest that an increase
      in extracellular glucose availability did not translate into increased
      intracellular glucose oxidation.

PMID- 16302287
TI  - Pharmacokinetics of a ginseng saponin metabolite compound K in rats.
AB  - The absorption, dose-linearity and pharmacokinetics of compound K, a major
      intestinal bacterial metabolite of ginsenosides, were evaluated in vitro and in
      vivo. Using the Caco-2 cell monolayers, compound K showed moderate permeability
      with no directional effects, thus suggesting passive diffusion. After intravenous
      dose (i.v.; 1, 2, and 10 mg/kg), no significant dose-dependency was found in Cl
      (17.3-31.3 ml/min/kg), Vss (1677-2744 ml/kg), dose-normalized AUC (41.8-57.8
      microg.min/ml based on 1 mg/kg) and t1/2. The extent of urinary excretion was
      minimal for both i.v. and oral doses. The extent of compound K recovered from the
      entire gastrointestinal tract at 24h were 24.4%-26.2% for i.v. doses and 54.3%
      81.7% for oral doses. Following oral administration (doses 5-20 mg/kg), dose
      normalized AUC (based on 5 mg/kg) was increased at the 20 mg/kg dose (85.3
      microg.min/ml) compared with those at lower doses (4.50-10.5 microg.min/ml).
      Subsequently, the absolute oral bioavailability (F) was increased from 1.8%-4.3%
      at the lower doses to 35.0% at the 20 mg/kg dose. The increased F could be
      related to the saturation of carrier-mediated hepatic uptake and esterification
      of compound K with fatty acids in the liver.

PMID- 16302288
TI  - Gender differences in the pharmacokinetics of DA-6034, a derivative of
      flavonoids, in rats.
AB  - Gender differences in the pharmacokinetics of DA-6034 were evaluated after
      intravenous and oral administration at a dose of 50 mg/kg to male and female
      Sprague-Dawley rats. After intravenous administration to male rats, although the
      total area under the plasma concentration-time curve from time zero to time
      infinity of DA-6034 was not significantly different between male and female rats,
      the plasma concentrations of DA-6034 were lower from 30 min to 480 min, the mean
      residence time was significantly shorter (6.28 versus 12.2 min), the percentage
      of intravenous dose of DA-6034 excreted in 24 h urine as unchanged drug was
      significantly greater (14.4% versus 10.5% of intravenous dose). After oral
      administration, the pharmacokinetic parameters of DA-6034 were not significantly
      different between male and female rats.

PMID- 16302289
TI  - Effects of acute renal failure on the pharmacokinetics of DA-7867, a new
      oxazolidinone, in rats.
AB  - The pharmacokinetic parameters of DA-7867 were compared after intravenous and
      oral administration at a dose of 10 mg/kg to control rats and rats with acute
      renal failure induced by uranyl nitrate (rats with U-ARF). After intravenous
      administration in rats with U-ARF, the time-averaged total body clearance (Cl)
      was significantly faster (2.45 versus 0.932 ml/min/kg) than controls due to
      significantly faster nonrenal clearance (2.25 versus 0.855 ml/min/kg) in rats
      with U-ARF. The faster nonrenal clearance could be due to significantly greater
      gastrointestinal (including biliary) excretion; the amount of unchanged DA-7867
      recovered from the entire gastrointestinal tract at 24 h was significantly
      greater (30.3% versus 9.38% of intravenous dose) in rats with U-ARF. In rats with
      U-ARF, the Vss was significantly larger (1420 ml/kg compared with 580 ml/kg), but
      this was not due to a difference in plasma protein binding; the values were
      comparable between the two groups of rats. After oral administration to rats with
      U-ARF, the total area under the plasma concentration-time from time zero to time
      infinity (AUC) of DA-7867 was significantly smaller than the controls (2560
      microg min/ml versus 7440 microg min/ml), and this was not due mainly to a
      decrease in absorption from the gastrointestinal tract in rats with U-ARF.

PMID- 16302290
TI  - Requests for information by family and friends of cancer patients calling the
      National Cancer Institute's Cancer Information Service.
AB  - PURPOSE: To characterize their information needs, we examined the main topics of
      inquiry and discussion (subjects of interaction, SOI) of calls made by family and
      friends of cancer patients to the National Cancer Institute's Cancer Information
      Service's (CIS) 1-800-4-CANCER telephone information service and summarized
      differences by sociodemographic characteristics. DESIGN AND ANALYSIS: Data from
      26 789 family or friends of cancer patients calling the CIS between September
      2002 and August 2003 were analyzed. Frequencies, chi(2)'s, and logistic
      regressions were conducted to ascertain sample characteristics and
      sociodemographic correlates of each SOI. RESULTS AND CONCLUSIONS: The greatest
      proportion of calls concerned specific treatment information (54.9%) and general
      cancer site information (36.9%). Calls about specific treatment information were
      more likely among Asians, Hawaiian Natives, and Pacific Islanders (OR = 1.23,
      1.04-1.45), and those with higher education (OR = 1.21, 1.18-1.25). As age
      increased, the odds of calls about specific treatment information also increased
      (OR = 1.05, 1.03-1.07). Females (OR = 0.78, 0.72-0.84), Hispanics (OR = 0.77,
      0.67-0.89), African-Americans (OR = 0.68, 0.61-0.76), and American-Indians and
      Alaskan Natives (OR = 0.74, 0.58-0.93) were less likely to inquire about specific
      treatment information. Inquiries about general cancer site information were more
      likely among females (OR = 1.14, 1.06-1.23) and less likely among younger callers
      (OR = 0.95, 0.93-0.97) and African-Americans (OR = 0.87, 0.78-0.98). Differences
      in inquiries made by sociodemographic subgroups can inform the CIS' and other
      cancer-related organizations' efforts to develop and disseminate cancer
      information for family and friends of cancer patients.

PMID- 16302291
TI  - Depressive symptoms after lung cancer surgery: Their relation to coping style and
      social support.
AB  - Lung cancer patients may experience greater emotional distress than patients with
      other cancers. Studies have shown social support to predict adjustment in other
      cancers, but findings among lung cancer patients have been equivocal. Coping
      style has been shown to predict distress among lung cancer patients, but has not
      been examined in the context of social support. We examined coping style and
      social support as predictors of depressive symptoms one week after surgery among
      119 patients with non-small cell lung cancer. The Beck Depression Inventory was
      the primary outcome measure. Predictors included age, ECOG performance status,
      stage of disease, and measures of adaptive coping, less adaptive coping,
      Directive instrumental social support and Nondirective instrumental social
      support. Results indicated that 29% of lung cancer patients had scores above a
      standard cutoff for clinically significant depression. Results also showed that
      depressive symptoms were directly related to use of less adaptive coping methods
      and Directive instrumental social support, inversely related to age and use of
      adaptive coping methods, and unrelated to nondirective social support, stage of
      disease and performance status. Results extend previous findings by showing that
      adaptive coping methods are related to severity of distress, and that the
      benefits of social support may depend on the characteristics of that support.

PMID- 16302292
TI  - Cancer-related beliefs and health behavior change among breast cancer survivors
      and their first-degree relatives.
AB  - It is unclear why some cancer survivors and their relatives are motivated by the
      (personal or vicarious) cancer experience to make positive health behavior
      changes while others are not. Consistent with Leventhal's Commonsense Model, we
      hypothesized that breast cancer survivors and their first-degree relatives (FDRs)
      would change behaviors they believed: (1) had caused the survivor's cancer or (2)
      could prevent a future cancer incidence. Sixty-five breast cancer survivors
      (stages 0-III) and 33 FDRs were recruited. Assessments occurred within three
      months of the survivor completing treatment (i.e. all surgery, chemotherapy, and
      radiation) and again three months later. Findings indicate that survivors who
      believed that unhealthy diet, insufficient exercise, or alcohol consumption
      contributed to their cancer were more likely to modify the relevant behavior.
      Likewise, survivors were more likely to implement healthy changes they believed
      would ward off a recurrence. Findings were similar when data from FDRs was added
      to the sample. Thus, healthy lifestyle changes after a personal (and possibly a
      vicarious) cancer diagnosis are tied to whether individuals believe changes can
      affect cancer outcomes. Given the role of health behavior change in reducing
      medical risks, these findings have important implications for maintaining the
      health of cancer survivors.

PMID- 16302293
TI  - Approachable award-winner.

PMID- 16302294
TI  - Looking at US versus European exit opportunities.

PMID- 16302295
TI  - Virtual reality: the promise and pitfalls of going virtual.

PMID- 16302296
TI  - Modern management of myocardial infarction: introduction.

PMID- 16302297
TI  - [Treatment concepts for fractures of the thoracolumbar junction and lumbar
      spine].
AB  - Thoracolumbar vertebral fractures are not only characterized by frequent
      osteoligamentous instability, but also often by irreversible damage to to the
      intervertebral disk. Treatment guidelines can be formulated based on an accurate
      classification system. In addition to reconstructing the axis of rotation, it is
      crucial that the width of the spinal canal be restored when neurological deficits
      are present. Both indirect dorsal compression and ventral endoscopically guided
      direct decompression are equally of decisive importance. To achieve long-term
      stability with as little corrective loss as possible, the ventral column
      absorbing pressure is surgically stabilized by diligently resecting a destroyed
      intervertebral disk and vertebral fragments and replacing it with a
      corticocancellous bone graft or cage. The goal should always be to keep the
      fusion length as short as possible.

PMID- 16302298
TI  - [Diagnosis and treatment of disorders of the foot in children].
AB  - During the skeletal development of the axis and foot of the child physiological
      specialties can occur. Those are thick fatty sole, increased valgus in the ankle
      joint, tibial varus as a toddler with first varus, later on valgus in the knee,
      increased laxity of the ligaments, increased anteversion of the femoral neck with
      "kneeing in" and "toeing in", and with knees first in flexion, later on
      hyperextension. The knowledge of those specialties is important to be able to
      diagnose and treat deformities of the foot during childhood. Included are club
      foot, flexible flatfoot, vertical talus, pes adductus, equinus, cavus foot and
      talipes calcaneovalgus. If treated at the right time, those disorders of the feet
      can resolve completely. If an operation can't be avoided, the indication has to
      be chosen with care.

PMID- 16302299
TI  - China: the air pollution capital of the world.

PMID- 16302300
TI  - How Vioxx is changing US drug regulation.

PMID- 16302301
TI  - Fever: when to worry.

PMID- 16302302
TI  - Vaccine helps prevent pneumonia and meningitis.

PMID- 16302303
TI  - Management of cough in advanced cancer.
AB  - Cough is a common symptom in cancer, with causes that can be benign or malignant.
      When severe, it affects patients' quality of life and well being. Treatment
      begins with a detailed history and careful physical examination, followed by
      chest imaging. Managing cough is directed at correcting the reversible causes.
      Empiric treatment of cough is valuable in both reversible and irreversible
      causes. We prefer hydrocodone as first-line empiric treatment, but when the cough
      is resistant to this, our second-line therapy would be the addition or
      substitution of benzonatate. Bronchodilators, as well as corticosteroids, are
      commonly employed in our practice and can be useful in unsuspected bronchospasm.

PMID- 16302304
TI  - CBT, drugs effective for insomnia.

PMID- 16302305
TI  - [Acute hepatitis associated to amoxicillin-clavulanic acid combination].

PMID- 16302306
TI  - [EKG changes in a patient with respiratory infection].

PMID- 16302307
TI  - [Empyema caused by Fusobacterium necrophorum].

PMID- 16302308
TI  - [HIV-1 infection and inflammatory bowel disease].

PMID- 16302309
TI  - [Necrotizing fasciitis due to a brachial plexus block].

PMID- 16302310
TI  - [Liver abscess caused by Klebsiella oxytoca].

PMID- 16302311
TI  - [How does the infectious spondylodiscitis appear?].

PMID- 16302312
TI  - Functional devices.

PMID- 16302313
TI  - Substance abuse treatment in the Commonwealth of Massachusetts: gaps,
      consequences and solutions.
AB  - This issue brief outlines five strategies for improving the quality of treatment
      in Massachusetts: (1) Engaging detoxification clients in a broader continuum of
      treatment, (2) Improving retention in treatment, (3) Providing client/family
      centered services, (4) Increasing the use of evidence-based treatment approaches,
      and (5) Supporting recovery to address the chronic nature of substance use
      disorders. These strategies are essential to maximizing the impact of our
      substance abuse dollars. We need to do it right and then expand access to
      treatment more broadly and fill the treatment gap. Although not the focus of this
      report we need to think harder about upfront prevention and efforts to encourage
      more people to seek care. Part of the public strategy also requires better
      coordination between BSAS, MassHealth, provider organizations, and other state
      agencies, including criminal justice and mental health agencies. Through these
      efforts we can reduce the costs and consequences of substance abuse and build a
      healthier, more productive community.

PMID- 16302314
TI  - Supplier discretion over provision: theory and an application to medical care.
AB  - Suppliers who are better informed than purchasers, such as physicians treating
      insured patients, often have discretion over what to provide. I show how, when
      the purchaser observes what is supplied but neither the recipient type nor the
      actual cost incurred, optimal provision differs from what would be efficient if
      the purchaser had full information, weather or not the supplier can extract
      informational rent. The analysis is applied to, among other things, data on tests
      for coronary artery disease and to Medicare diagnosis-related groups defined by
      the treatment given, not just the diagnosis, illustrating the biases in provision
      that result.

PMID- 16302315
TI  - More answers on reinsurance.

PMID- 16302316
TI  - [Musculoskeletal disorders in occupational health. Bologna, Italy 22-24 October
      2002, meeting proceedings].

PMID- 16302317
TI  - The UNESCO Bioethics Declaration 'social responsibility' principle and cost
      effectiveness price evaluations for essential medicines.
AB  - The United Nations Scientific, Education and Cultural Organisation (UNESCO) has
      commenced drafting a Universal Bioethics Declaration. Some in the relevant UNESCO
      drafting committee have previously desired to restrict its content to general
      principles concerning the application (but not necessarily the goals) of science
      and technology. As potentially a crucial agenda-setting statement of global
      bioethics, however, it is arguable important the Universal Bioethics Declaration
      transparently address major bioethical dilemmas in the field of public health,
      such as universal access to affordable, essential medicines. Article 13 (Social
      Responsibility) of the Preliminary Draft Universal Bioethics Declaration states:
      'Any decision or practice shall ensure that progress in science and technology
      contributes, wherever possible, to the common good, including the achievement of
      goals such as: (i) access to quality health care and essential medicines,
      including for reproductive health and health of children.' Cost effectiveness
      pricing systems, such as that most notably used in Australia's Pharmaceutical
      Benefits Scheme (PBS), arguably represent one of the most scientifically
      effective mechanisms whereby public monies may be utilised to assist in the
      provision of medicines for the common good. They contain two essential elements:
      first, a process of scientific evaluation of objectively demonstrated therapeutic
      significance, and then, a fiscal lever (the government reimbursement price)
      attached to that evaluation. It is now well established that the US
      Pharmaceutical Research and Manufacturers Association (Pharma), through the
      assistance of the US Trade Representative (USTR), saw the Australia United States
      Free Trade Agreement (AUSFTA) as an opportunity to fulfill a legislative mandate
      to 'eliminate' the cost-effectiveness pricing system in Australia's PBS. One of
      the most remarkable features of the arguments raised against the PBS in this
      context was the fact that they made almost no reference to the normative
      discourse of bioethics or international human rights. Provisions such as Article
      13 in UNESCO's Universal Bioethics Declaration, although they will create no
      immediate obligations under international law, may play an extremely valuable
      role in legitimising the use of bioethical and human rights concepts in access to
      medicines debates surrounding multilateral and bilateral international trade
      deals such as the AUSFTA.

PMID- 16302318
TI  - Financial incentives, cross-purposes, and moral motivation in health care
      provision.
AB  - Financial incentives and disincentives are fundamental to a category of
      proposals, usually characterised as forms of managed care, whereby the pecuniary
      interests of health care providers are directly affected by their clinical
      decision-making. Presently, Australian health care administrators and private
      insurers are adopting financial incentives as a means of ensuring provider
      compliance with 'health outcome' and cost-constraint objectives. To the extent
      that this has occurred, health-care relationships are transformed to emulate,
      more closely, a commercial transaction. This paper questions the ideological
      assumptions which inform the use of financial incentives in the health care
      domain and raises concerns with regard to the potential for financial incentives
      to undermine the moral integrity of clinical decision-making. It also challenges
      the legitimacy of rationing health care resources through the use of this
      measure, particularly when adopted by private insurers of health care.

PMID- 16302319
TI  - Best interests, dementia, and end of life decision-making: the case of Mrs S.
AB  - In this paper, I present an ethical analysis of the case of an elderly woman with
      dementia, Mrs S. The hospital treating Mrs S sought to cease her dialysis
      treatment despite Mrs S's family's protestations that continuing the treatment
      was in her best interests. Assuming Brock's framework as a theoretical
      background, I consider the case in terms of three questions. Firstly, was 'best
      interests' the appropriate basis for deciding on a course of action in this
      situation? Secondly, assuming the appropriateness of a best interests principle,
      was it in Mrs S's best interests for the dialysis treatment to be withdrawn as
      the hospital suggested? And thirdly, if it was in Mrs S's best interests for
      dialysis to be withdrawn, was the hospital right to pursue this course of action
      in light of the family's disagreement? Based on the changes to the patient's
      'self' associated with dementia, I argue that a best interests principle was
      appropriate, that continuing dialysis was not in Mrs S's best interests, and that
      the hospital should have pursued cessation of treatment, even in light of the
      family's contrary wishes.

PMID- 16302320
TI  - The ethics of complementary and alternative medicine research: a case study of
      traditional Chinese medicine at the University of Technology, Sydney.
AB  - This article considers various approaches used in complementary and alternative
      medicine research, and discusses the challenges that reviewing such research
      poses for Human Research Ethics Committees. Drawing on our experience with the
      University of Technology Sydney HREC, we offer some suggestions about how ethical
      principles governing conventional medical research can be applied in the context
      of research in complementary and alternative medicine. We argue that effective
      HREC review requires members to gain familiarity with such research, which helps
      ensure that such research is conducted rigorously and ethically.

PMID- 16302321
TI  - Commentary on C Zaslawski and S Davis, 'The ethics of complementary and
      alternative medicine research'.

PMID- 16302322
TI  - Easing abortion's pain: the new fight to help the unborn.

PMID- 16302323
TI  - Most researchers favor NIH policy that requires less information, survey finds.

PMID- 16302324
TI  - Playing it safe with research risk: if you fail to follow the rules, you could
      conduct an entire project and be forbidden to publish the results.

PMID- 16302325
TI  - An observer-blind parallel-group, randomized, multicentre clinical and
      microbiological study of a topical clindamycin/zinc gel and a topical clindamycin
      lotion in patients with mild/moderate acne.
AB  - INTRODUCTION: A topical acne treatment in which clindamycin phosphate equivalent
      to 1% clindamycin is presented in a gel formulation has received marketing
      authorizations in a number of EU and non-EU countries. Clindamycin/zinc gel
      contains zinc acetate in a formulation that reduces systemic absorption of
      clindamycin through the skin. OBJECTIVES: To compare the efficacy and safety of a
      1% clindamycin/zinc gel when applied to the face once daily or twice daily with a
      1% clindamycin lotion applied twice daily for 16 weeks in patients with mild to
      moderate acne vulgaris. METHODS: This was a randomized, comparative, observer
      blind, parallel-group, multicentre study involving 246 acne patients. RESULTS:
      The study demonstrated therapeutic similarity between clindamycin/zinc gel
      applied once and twice daily with clindamycin lotion applied twice daily. All
      three regimens produced a gradual and time-dependent reduction in inflamed
      lesions, non-inflamed lesions and overall grade. Side effects were similar and
      minimal, consisting predominantly of mild irritant dermatitis. All regimes
      produced a time-related significant reduction in skin surface and follicular
      Propionibacterium spp. and Micrococcaceae. The emergence of resistant strains was
      less than 5% and was similar with all three regimes. CONCLUSION: The equivalent
      efficacy and safety of clindamycin/zinc gel either once or twice daily to
      clindamycin lotion twice daily has been demonstrated. It is suggested that a
      treatment regime of one application per day may significantly enhance compliance
      and thus treatment success in acne patients.

PMID- 16302326
TI  - The William Harvey stamp.

PMID- 16302327
TI  - Caleb Hillier Parry (1755-1822).

PMID- 16302328
TI  - Quackery and scientific medicine in Georgian England.

PMID- 16302329
TI  - The relation between swelling properties and cross-linking of hydrogels designed
      for colon-specific drug delivery.
AB  - Copolymers of 2-hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA)-based
      hydrogels containing 5% and 10% of a cross-linking agent were studied as drug
      delivery systems. Terephthalic acid was covalently linked with HEMA, abbreviated
      as CA (cross-linking agent). Free radical cross-linking copolymerization of HEMA
      and methacrylic acid (MAA) in three different molar ratios, mixed with a
      particulate 3, 3-azobis (6-hydroxy benzoic acid) (ABHB) as an azo derivative of 5
      aminosalicylic acid with the various ratios CA as cross-linking agent were
      carried out with using 2, 2, Azobisisobutyronitrile as initiator at the
      temperature range 60-70 degrees C. The compositions of the cross-linked three
      dimensional polymers were determined by FTIR spectroscopy. Glass transition
      temperature of the network polymers was determined calorimetrically. The
      hydrolysis of drug-polymer conjugates was carried out in cellophane membrane
      dialysis bags containing an aqueous buffer solution (pH 7.4 and pH 1) at 37
      degrees C. The drug-release profiles indicate that the amount of drug release
      depends on its degree of swelling and cross-linking.

PMID- 16302330
TI  - Profiles in family nursing leadership: honoring the authors of family nursing
      textbooks.

PMID- 16302331
TI  - Comparison of MRI features of different grades of DCIS and invasive carcinoma of
      the breast.
AB  - The purpose of the study is to compare mammography and magnetic resonance (MR)
      mammography in detection and assessment of extent, of histologically proven
      ductal carcinoma in situ (DCIS) and to compare MR features of DCIS, with features
      of invasive carcinoma. Forty histopathologically proven and MR detected pure DCIS
      lesions were described and compared with 213 enhancing invasive carcinomas.
      Histopathological examination revealed 49 pure DCIS, MR detected 40 of them
      (81.6%). There was a good correlation between diameter measured on mammography,
      MR and histopathology. MR was able to detect additional foci. Ductal enhancement,
      a focal area or a mass were perceived in respectively 8 (20%), 8 (20%) and 24
      (60%) DCIS and in 0, 6 (2.8%) and 207 (97.2%) invasive lesions. Maximal contrast
      enhancement after 3 minutes was seen in 60.9% of DCIS and before 3 minutes in 61%
      of invasive masses. Signal intensity increase of more than 100% was seen in 76.9%
      of DCIS and in 91.1% of invasive carcinomas. DCIS had a wash out in 53.8% and
      invasive carcinomas in 65.3%. MR was able to detect 81.6% of DCIS. Diameter
      prediction was good on mammography and MR mammography. The only MR feature
      exclusively seen in DCIS was ductal enhancement.

PMID- 16302332
TI  - Diagnosis of inguinal bladder hernias: the current role of sonography.
AB  - We present a case of inguinal bladder hernia detected initially with sonography
      in an adult patient. Compared with digestive or omental hernias, inguinocrural
      bladder herniations are a rarer occurrence (1 to 4% of all cases). Their
      detection is nevertheless highly imperative in order to avoid inadvertent injury
      to the bladder during routine hemiorrhaphy. Since the advent of high frequency
      equipment, ultrasonography has become the essential method of diagnosing vesical
      hernias. It is simple and fast, totally non-invasive, inexpensive, and widely
      available.

PMID- 16302333
TI  - Fibrolamellar hepatocellular carcinoma in a 65-year-old woman: CT features.
AB  - A 65-year old woman with recurrent deep vein thrombosis underwent a CT scan of
      the upper abdomen for detection of underlying malignancy. A fibrolamellar
      hepatocellular carcinoma with extrahepatic subdiaphragmatic satellite lesion was
      found. This uncommon tumor has distinct clinical, pathological, radiological and
      prognostic features and therefore it is important to distinguish it from benign
      liver tumors, especially FNH, and from other malignant liver tumors such as
      conventional HCC. Though the tumor characteristically occurs in younger patients,
      our case proves that older patients can also be affected.

PMID- 16302335
TI  - Left ovarian Brenner tumor.
AB  - Ovarian Brenner tumors are uncommon neoplasms of the ovary, representing
      approximately 2% of all ovarian neoplasms. Nowadays there is general agreement
      that Brenner tumors are derived from the surface epithelium of the ovary or the
      pelvic mesothelium through transitional cell metaplasia. Association with other
      surface-derived neoplasms, either in the ipsilateral or contralateral ovary, is
      reported in 30% of the cases. We report a case of benign ovarian Brenner tumor
      and discuss the typical features on magnetic resonance imaging (MRI) and computed
      tomography (CT) scan as well as the differential diagnosis.

PMID- 16302334
TI  - Spurious absence of signal on 3D time-of-flight MR angiograms on 1 and 3 tesla
      magnets in cerebral arteries associated with a giant ophthalmic segment aneurysm:
      the need for alternative techniques.
AB  - There are many high-resolution MR angiographic techniques available today for the
      evaluation of circle of Willis. We report a case of bilateral aneurysms of the
      carotico-ophthalmic segment, the left one being a giant aneurysm, in a 41-year
      old woman. She underwent different MRA sequences on both 1 and 3Tesla magnets and
      a digital subtraction angiography. 3D time-of-flight angiograms can give spurious
      information on giant aneurysms and other techniques like phase contrast and
      dynamic contrast enhanced angiographies can supplement if not replace it. High
      field strength improves the objective quality of MR angiograms, but in the case
      of large aneurysms, intra aneurysmal and distal vessel signal loss can be a
      significant problem.

PMID- 16302336
TI  - Pachymeningitis in intracranial liquor hypotension syndrome.

PMID- 16302337
TI  - Pneumoparotitis.

PMID- 16302338
TI  - [MRI and metabolic brain pathology].

PMID- 16302339
TI  - [The radiologic contribution to surgical aspects of kidney tumors in children].

PMID- 16302340
TI  - [The thoraco-abdominal applications of MRI in the fetus].

PMID- 16302341
TI  - [Data transmission of images to clinicians: technical and organizational
      aspects].

PMID- 16302343
TI  - [The status of strategic choices in liver surgery and transplantation].

PMID- 16302342
TI  - [The use of diffusion imagery in pediatric neuroradiology].

PMID- 16302344
TI  - [Imaging in neonatal intestinal obstruction].

PMID- 16302345
TI  - [Urinary MRI in children].

PMID- 16302346
TI  - [Bone densitometry in pediatric practice].

PMID- 16302347
TI  - [Inflammatory digestive pathology: indications for computed tomography].

PMID- 16302348
TI  - [Which diagnostics and which technics in fetal neuro-MRI?].

PMID- 16302349
TI  - [Innovations in interventional pediatric neuroradiology].

PMID- 16302350
TI  - [What future for pediatric radiology].

PMID- 16302351
TI  - [What remains of small intestine transit in 2004?].

PMID- 16302352
TI  - [The uncertainties of hospital informatics].

PMID- 16302353
TI  - [Varicocele. The pediatric experience].

PMID- 16302354
TI  - [Inflammatory pathology of the digestive tract. Indications for ultrasonography].

PMID- 16302355
TI  - [Atypical glandular cells (AGC) on Papanicolaou smears--the great challenge of
      cervix screening programs].
AB  - The "grey zone" diagnostic category for glandular cells in the Bethesda System
      2001 (TBS 2001) has undergone significant modification since its last version in
      1991. PATIENTS: The aim of the study was to follow up patients with "atypical
      glandular cells of undetermined significance" (AGUS)/ "atypical glandular cells"
      (AGC), and adenocarcinoma cytological interpretation, based on a three-year
      material between 2000-2002 at the Department of Cytopathology of National
      Institute of Oncology, Hungary. The smears were reviewed and interpreted
      according to TBS 2001. Histological slides were reviewed and cytohistologic
      correlations were investigated. RESULTS: Out of 36193 conventional Papanicolaou
      smears, there were 276 AGC-NOS (AGUS, favour reactive in TBS1991) and 7 AGC
      favour neoplastic (AGUS, favour neoplastic in TBS 1991) (altogether 0.78%) and 35
      (0.1%) adenocarcinoma interpretations. Histology was available in 136 (AGC-NOS:
      106, AGC-favour neoplastic: 7 and adenocarcinoma: 23) cases. Among the followed
      106 patients with AGC-NOS, there were 24 cases with concurrent "grey zone"
      squamous, ASC-US, interpretation. Clinically significant lesions were found in
      5/7 (71%) of cases of the AGC-favour neoplastic group, and in 27/106 (25%) of the
      all AGC-NOS group, the difference is statistically significant. This ratio is
      16/82 (20%) in the AGC-NOS only cases, while 11/24 (46%), in the AGC-NOS with
      concurrent ASC-US cases, the difference is statistically significant. The high
      grade lesions were mostly squamous. CONCLUSION: The results suggest that AGC-NOS
      with concurrent ASC-US interpretation represent a group of potential patients
      with statistically significant higher risk of clinically significant (among them
      high-grade) lesions.

PMID- 16302356
TI  - [The effect of controlled and uncontrolled dynamic lower extremity training in
      the rehabilitation of patients with chronic obstructive pulmonary disease].
AB  - Pulmonary rehabilitation has become a part of the integrated management of
      patients with chronic obstructive pulmonary disease (COPD). The lower extremity
      dynamic training has been proved to be the most effective element of the program.
      OBJECTIVE: Does the supervised training have more favorable effect in case of
      similar program? PATIENTS AND METHODS: In two groups: 54 patients, supervised
      (group K, n = 22) and not supervised (group NK, n = 32) by physiotherapists,
      chosen at random have been investigated. Both groups consisted of hospitalized
      patients of the same severity (forced expiratory volume in one second) [FEV1
      (average +/- SD)]: K: 51.0 +/- 16.1 vs. NK: 51.9 +/- 15.6% pred). Group K
      performed physiotherapist-supervised cycling training in the Pulmonology
      Ambulance Unit 3-4 times a week for 45 minutes doing an 8-week period and group
      NK performed training in the form of cycling, stepping on stairs or dynamic
      walking at home with the same duration, weekly periodicity and time interval.
      RESULTS: After rehabilitation vital capacity (VC) (K: 3.0 +/- 0.8 vs. 3.3 +/- 0.7
      l, p < 0.05), emphysema ratio (RV/TLC): K: 53.5 +/- 10.1 vs. 51.6 +/- 9.9, p <
      0.05) in the supervised group, and alveolar volume (VA) in the not supervised
      group (NK: 4.3 +/- 0.9 vs. 4.7 +/- 0.9 l, p < 0.05) significantly improved.
      Improvement of exercise capacity was more effective in group K (K: 92.7 +/- 33.9
      vs. 106.4 +/- 34.5 W, p < 0.001; NK: 95.8 +/- 36.7 vs. 99.9 +/- 35.1 W, p <
      0.05). In both groups aerobic capacity (VO2: K: 1.2 +/- 0.4 vs. 1.3 +/- 0.4
      l/min, p < 0.01, NK: 1.1 +/- 0.4 vs. 1.2 +/- 0.4 l/min, p < 0.01; VO2/kg: K: 16.1
      +/- 5.5 vs. 17.5 +/- 5.8 ml/kg/mm, p < 0.01, NK: 16.2 +/- 5.3 vs. 16.7 +/- 4.8
      ml/kg/ min, p < 0.01) and anaerobic threshold level [AT (pred VO2%)] (K: 36.6 +/-
      9.8 vs. 42.8 +/- 10.2%, p < 0.001; NK: 40.8 +/- 12.0 vs. 44.6 + 11.6%, p < 0.001)
      significantly improved. Heart rate reserve: (K: 17.7 +/- 22.7 vs. 28.8 +/- 31.5
      l/min, p < 0.01; NK: 20.4 +/- 21.2 vs. 25.0 +/- 21.6 l/min, p < 0.01) improved at
      the same level of exercise. The Borg scale of dyspnea (0-10): (K: 6.4 +/- 2.5 vs.
      5.7 +/- 2.7, p < 0.05; NK: 7.5 +/- 1.8 vs. 6.9 +/- 2.2, p < 0.05) was reduced and
      quality of life score (0-24): K: 11.5 +/- 0.7 vs. 9.0 +/- 2.8, p < 0.005; NK:
      11.6 +/- 2.3 vs. 7.0 +/- 1.9, p < 0.005) was improved. CONCLUSION: In both group
      dynamic lower extremity training caused improvement in exercise capacity. The
      favorable metabolic effect of training was shown by the change of anaerobic
      threshold resulting in less carbon dioxide production during analogous exercise.
      This reduction led to less ventilation reducing the work of breathing in
      supervised group. The more favorable adaptation taking place in the group
      supervised by physiotherapists might have resulted from the controlled higher
      intensity of the training.

PMID- 16302357
TI  - [Molecular detection and sequence analysis of hepatitis A virus (HAV) in two
      outbreaks in 2004 in North East Hungary].
AB  - INTRODUCTION: Hepatitis A virus (HAV) is the most important cause of acute
      infectious hepatitis worldwide. In Hungary, the reported number of HAV infections
      decreasing in the last decades, however, in every year approximately 500-800 new
      cases occur. In Hungary, particularly in North East region not only sporadic
      cases but also outbreaks of HAV are happen from time to time. Serology is
      routinely used laboratory method for diagnosis of HAV infections, although, there
      was no direct molecular detection and sequence analysis for the circulating HAV
      strains in Hungary. AIMS: Author's aims were to detection and genetic
      characterization of hepatitis A virus in outbreaks of hepatitis by molecular
      methods for reason of molecular epidemiology in Hungary. MATERIALS AND METHODS:
      Sera samples from symptomatic patients were tested from two acute hepatitis
      outbreaks in two settlements (Hajduboszormeny and Kazsmark) in North East Hungary
      in 2004 by enzim-immunoassay (EIA) and reverse transcription-polymerase chain
      reaction (RT-PCR). RESULTS: Sera in 58 (100%) and 4 (28.6%) symptomatic patients
      were positive in outbreaks of Hajduboszormeny and Kazsmark by HAV IgM EIA,
      however, 4 (57.1%) and 2 (66.6%) HAV IgM positive samples were positive by RT
      PCR. By sequence analysis, outbreaks caused by the same hepatitis A virus which
      belongs to genotype I, subtype IA. These viruses had 98.4% nucleotide identity to
      IT-SCH-00 virus detected in year 2000 in Italy the closest match in GenBank.
      CONCLUSIONS: Methods of molecular biology give new opportunity for surveillance
      of infectious diseases in public health. Firstly characterized hepatitis A
      viruses in Hungary show that the subtype IA have an important epidemiological
      role in outbreaks. It is also suggested that genotype IA HAV play a part in
      sporadic HAV cases in endemic region in Hungary, too.

PMID- 16302358
TI  - [Cycle vomiting syndrome as a clinical appearance of eosinophilic
      gastroenteritis].
AB  - The authors report the case study of a 16-year old boy who presented with cyclic
      vomiting syndrome. His main clinical symptoms had been unpredictable sudden-onset
      vomiting episodes interrupting long episodes of full health lasting for several
      months since the patient was a toddler. Histological results of the upper tract
      endoscopy showed eosinophil gastroenteritis with long-existing, undetected cow
      milk allergy as the likely underlying reason. The patient became symptomless
      following the elimination of cow milk from his diet. The symptoms did not recur
      following a cow milk load test carried out half a year later, and the patient
      continues to be symptomless after more than one-year of continuous cow milk
      consumption. In this paper, the authors would like to highlight the importance of
      EG int the differential diagnosis of any chronic, recidive gastrointestinal
      symptoms and discuss the likely underlying causes of EG in paediatrics.

PMID- 16302359
TI  - [Hungarian pioneers in contact lens development].

PMID- 16302360
TI  - [Imre Magyar (1910-1984), the belletrist physician].

PMID- 16302361
TI  - [The 125 years history of Science and its future].

PMID- 16302362
TI  - "Mom, I think I'm really sick".

PMID- 16302363
TI  - Ethics are everything.

PMID- 16302364
TI  - Loose in the caboose: restraining for keeps.

PMID- 16302365
TI  - Underground attack. How London's disaster plan worked for EMS.

PMID- 16302366
TI  - Bugs without borders. What EMS needs to know about emerging infections.

PMID- 16302367
TI  - Cardiac arrest care: out with the old CPR, in with the new.

PMID- 16302368
TI  - Drug seekers: do you recognize the signs?

PMID- 16302369
TI  - Carbon monoxide poisoning: incidence, diagnosis & treatment.

PMID- 16302370
TI  - Invent your future.

PMID- 16302371
TI  - Hawaii air ambulance faces unique challenges.

PMID- 16302372
TI  - Baseball, lobsters, and our genetic relationship to the banana. Presidential
      address given at the BAFS AGM on 1 june 2005.

PMID- 16302373
TI  - Homicide in the Canadian prairies: spousal killers, amnesia and self-harm.
AB  - This study identifies the incidence of claims of amnesia in homicide offenders
      and explores the associations with other psychopathology. It is a retrospective
      file review and analysis of 901 nonselective, adult men convicted of homicide.
      Claims of amnesia occurred in 31% (280) of the total homicide population and 46%
      of spousal killers compared to 28% of non-spousal killers. Claims in both groups
      were significantly associated with alcohol use and in the spousal group with
      actual or threats of self-harm at the time of the killing. Spousal killers were
      more likely to claim some degree of amnesia for the homicide and engage in or
      threaten self-harm after the killing. These and other features suggest that some
      spousal killers may have borderline personality traits/disorders. This study
      proposes a new classification for spousal homicides.

PMID- 16302374
TI  - The Galbraith judgment and the defence of diminished responsibility in Scotland.
AB  - New case law on diminished responsibility in Scotland (Galbraith v. HM Advocate
      2001) re-defined the defence and clarified the role of expert witnesses. We
      examined how this judgment affected the use of the defence, provision of expert
      evidence and the outcome of trials. We studied homicide cases in one area of
      Scotland in the year before and the year after the new judgment. Results
      indicated little change in the number of cases where the defence was used, but a
      difference in how psychiatrists set out their opinions.

PMID- 16302375
TI  - Factors influencing treatment entry in sex offenders against children.
AB  - The study examined the psychosocial characteristics of 99 sex offenders against
      children referred for treatment to a forensic community sex offender programme.
      The subjects had high levels of substance misuse problems and personality
      disorder but low rates of Axis I disorder. Subjects accepted for treatment could
      not be distinguished from those rejected as unsuitable on the Child Sex
      Questionnaire (CSQ) (Beckett et al., 1994), apart from the question on whether or
      not subjects believed it was wrong to have sexual contact with children.
      Substance misuse, antisocial personality disorder and past criminal history did
      not determine whether subjects were accepted or rejected. Differences in scores
      on actuarial measures of risk (STATIC-99) were also not significant. Clinicians'
      ratings of motivation, level of denial and poor social skills were the key
      factors determining rejection for treatment. Reconviction rates in the treatment
      group were low (7%) at five-year follow-up.

PMID- 16302376
TI  - An audit of urgent referrals by the Procurator Fiscal to the Tayside Forensic
      Psychiatric Service.
AB  - This study describes the demographic, offence and diagnostic characteristics of
      subjects referred by the Procurators Fiscal operating from three courts in
      Tayside, Scotland. A comparison is made of referrals made between 1988 to 1995
      and 1997 to 1998. There was an increased rate of referral on an urgent basis over
      time, primarily involving patients already in contact with the psychiatric
      services, 37% of whom were detained and admitted to hospital. This urgent
      assessment ensured that mentally-disordered offenders were not remanded in
      custody simply for the preparation of a report, and it allowed an early
      assessment to be made regarding the suitability for diversion from prosecution.
      This outcome is compatible with guidelines issued by the Home Office in 1990
      (Home Office, 1990).

PMID- 16302377
TI  - Shoplifting in the mentally ill: the role of bipolar affective disorder and
      mental retardation.
AB  - This study explores shoplifting behaviour in mentally ill patients, and evaluates
      the association between shoplifting and different mental illnesses in a local
      Chinese population. A comparison is made between shoplifting offenders and a
      matched control group of non-offenders among the psychiatric patients registered
      at a university department of psychiatry. Major depression, bipolar affective
      disorder (BAD) and mental retardation (MR) are the most common diagnoses among
      mentally ill shoplifters, while patients with a diagnosis of BAD or MR are at
      higher risk of committing an offence than patients with other diagnoses. Bipolar
      affective disorder has not been described as a risk factor for shoplifting
      behaviour in the psychiatric literature. Such a possibility should be seriously
      considered in the psychiatric assessment of shoplifting cases.

PMID- 16302378
TI  - Neck structure injuries in Hanging--comparing retrospective and prospective
      studies.
AB  - Deaths due to hanging are common among suicides. Various studies in the forensic
      literature have reported considerable differences in the frequency of hyoid bone
      or thyroid cartilage fractures and injuries to the musculature and the
      vasculature of the neck. Some important reasons to which these variations could
      be attributed include: lack of a common method for examination of neck
      structures, varying degrees of thoroughness in examining the neck structures and
      lack of seriousness in the documentation of the findings (as cases of hanging are
      almost always suicidal) thus affecting the results of retrospective studies. The
      present study was conducted retrospectively (1994 to 1999) and prospectively
      (2000 to 2003) on 108 cases of hanging. Seventy-one per cent of the cases were
      male and 29% female, aged between 15 to 60 years. Hanging was typical in 20% of
      cases and atypical in 80%; it was complete hanging in 46% of cases and incomplete
      in 54% of cases. Neck structure fractures were found to be more common in
      atypical complete hangings; the incidence was found to be 10% in the
      retrospective group and 27% in the prospective group. Contusions and lacerations
      of musculature were found in 20% of cases in the retrospective group and 34% in
      the prospective group, thus stressing the need for thorough postmortem
      examinations and meticulous documentation of the findings.

PMID- 16302379
TI  - Redeveloping secure psychiatric services for women.
AB  - Historically, a substantial proportion of women have been unduly detained in
      conditions of high security in England due to the lack of suitable alternative
      facilities. There have been no studies that have comprehensively examined the
      individual needs of these women in relation to their placement needs. A cross
      sectional survey was undertaken of the individual and placement needs of all
      females detained in the three high security psychiatric hospitals (HSPHs) in
      England on 18th October 1999. Whilst there are clearly differences in
      accommodation needs among the women, those requiring lower secure services are
      significantly less likely to have needs in relation to violence (OR 0.29, 95% CI
      0.14-0.62) and drugs (OR 0.29, 95% CI 0.12-0.67) when length of stay is taken
      into account. They also have lower security, treatment and dependency needs than
      women still requiring HSPH treatment. A significant reorganisation of services is
      required. There is a need to gain further understanding of the relationships
      between traumatic histories, clinical presentation and antisocial behaviour and
      how these impact on assessed risk, treatment and care needs and outcome. The
      special needs of these women should be considered a priority when developing
      treatment and care packages.

PMID- 16302380
TI  - Traumatic death from rival gang violence in Rivers State, Nigeria.
AB  - A prospective autopsy study in Rivers State, Nigeria, was undertaken to evaluate
      the patterns of death as a result of rival gang clashes and to highlight the
      menace of rival gang violence. Between 1 January 1999 and 31 December 2003 medico
      legally autopsied bodies in Rivers State, where death was the result of gang
      violence, were studied after being served with the coroner's form. In all cases,
      standard autopsy procedures were adopted and reports were issued. A total of 58
      bodies were autopsied for the study. Three (5.2%) were females and 55 (94.8%)
      were males, giving a female to male ratio of 1:18.3. The age group of 10-29 years
      recorded the highest frequency of death (65.6%) with a peak in the age group 20
      29 years (39.7%). Gang violence and politically motivated mob action were the
      most common precipitating factors (60.3% and 20.7% respectively). Firearms
      (41.4%) was the most common method applied for the killing. Death was more common
      in the rural areas of Rivers State. Gang clashes, volatile political rallies,
      illegal drug peddling and illegal oil bunkering should be banned and stringent
      laws be passed. Such laws should also cover gun handling and should be enforced.

PMID- 16302381
TI  - Underlying factors for the rapid increase of suicide in Mie Prefecture, Japan.
AB  - The number of suicides in Japan increased from about 22,000 per year during the
      period 1988 to 1997 to over 30,000 since 1998. The number of suicides has also
      been increasing in Mie Prefecture. In the present study we examined the incidence
      and the circumstances for all suicidal cases during the seven-year period, 1996
      2002, that were reported to Mie Prefectural Police Headquarters. In Mie
      Prefecture, the number of suicides per year averaged 421 cases: from a minimum of
      319 in 1997 to a maximum of 501 in 1998. The most frequent month for suicides was
      July, while the lowest number occurred in February. Suicide was most common in
      the 50-59 year age group in men, and in the 70-79 year group in women. Regarding
      the means of suicide, hanging was the most frequent (61.6%) in both sexes.
      Psychiatric disorders were the most serious causative factors in all generations,
      accounting for 23.8% in general but being especially prevalent in the younger
      generation of people under 39 years. Further reasons for suicide were economic
      problems for the 40-64 age-group in men and suffering from illness for the
      elderly age-groups in both sexes. In order to prevent suicide, urgent strategies
      for effective medical treatments and improved working circumstances are required.

PMID- 16302382
TI  - Arrhythmogenic right ventricular cardiomyopathy/dysplasia mimicking rape
      homicide: a case report.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC), also known as
      arrhythmogenic right ventricular dysplasia, is a known cause of sudden
      unexplained death in young, otherwise healthy adults. In the forensic setting,
      several cases of fatal ARVC have been reported, mostly occurring during physical
      exercise. However, a very few cases present where the death scene is mistaken for
      a homicide. We report here the case of a 23-year-old woman, found dead, lying in
      the snow on an isolated property. The woman's genitals were exposed, with her
      trousers down over her thighs. Rape homicide was strongly suspected, but autopsy
      findings proved otherwise.

PMID- 16302383
TI  - An autopsy case of sudden death in a boy with primary pulmonary hypertension: a
      case report.
AB  - We report a rare autopsy case of sudden death due to primary pulmonary
      hypertension. A seven-year-old boy, who had been diagnosed with primary pulmonary
      hypertension at the age of four years, died suddenly. Forensic autopsy and
      histopathologic examination revealed extensive obstruction of small muscular
      pulmonary arteries by plexiform lesions and concentric intimal thickenings,
      compatible with primary pulmonary hypertension. We concluded that plexiform
      lesions of pulmonary arteries produced right ventricular hypertrophy and
      dilatation, decreased the preload of the left ventricle and subsequently led to
      biventricular failure. This autopsy and histopathologic examination suggested a
      possible pathophysiologic mechanism of sudden death due to primary pulmonary
      hypertension in a child.

PMID- 16302385
TI  - Guided light and diffraction model of human-eye photoreceptors.
AB  - The photoreceptors of the living human eye are known to exhibit waveguide
      characteristic features. This is evidenced by the Stiles-Crawford effect observed
      for light incident near the pupil rim, and by the directional component of light
      reflected off the retina in the related optical Stiles-Crawford effect. We
      describe a model for the coupling of light to/from photoreceptors on the basis of
      waveguide theory that includes diffraction between the eye pupil and the
      photoreceptor apertures, and we show that valuable insight can be gained from a
      Gaussian approximation to the mode field. We apply this knowledge to a detailed
      study of the relationship between the Stiles-Crawford effect and its optical
      counterpart.

PMID- 16302384
TI  - Color category influences heterogeneous visual search for color.
AB  - Many previous studies have revealed chromatic characteristics of visual search
      using relatively simple stimuli. They suggested that color difference between a
      target and distractors was a crucial factor. However, it may not be applicable to
      natural environments that contain numerous colors. This study demonstrates the
      existence of a color-category effect on heterochromatic visual search. Color
      differences between a target and distractors were constant in the OSA uniform
      color scales; however, the search times varied widely. This suggests that color
      differences alone do not explain search performance. To clarify the mediation of
      a higher-order categorical color process, search times were analyzed using 11
      basic colors. When the color category of a target was shared by a larger number
      of distractors, the search performance declined. However, when the color category
      of a target was not shared with distractors, the target was easily detected. The
      results suggest that heterochromatic stimuli could be segregated by categorical
      color perception.

PMID- 16302386
TI  - Spatial coherence in strongly scattering media.
AB  - We study the spatial coherence of an optical beam in a strongly scattering medium
      confined in a slab geometry. Using the radiative transfer equation, we study
      numerically the behavior of the transverse spatial coherence length in the
      different transport regimes. Transitions from the ballistic to the diffusive
      regimes are clearly identified.

PMID- 16302387
TI  - Comparison of reconstruction algorithms for optical diffraction tomography.
AB  - A recently developed inverse scattering algorithm [A. J. Devaney and M. Dennison,
      Inverse Probl., 19, 855 (2003) and M. Dennison and A. J. Devaney, Inverse Probl.,
      20, 1307 (2004)] is described and applied in a computer simulation study of
      optical diffraction tomography (ODT). The new algorithm is superior to standard
      ODT reconstruction algorithms, such as the filtered backpropagation algorithm, in
      applications employing a limited number of scattering experiments (the so-called
      limited-view case) and also in cases where multiple scattering occurs between the
      object being interrogated and the (known) background in which the object is
      embedded. The new algorithm is compared and contrasted with the filtered
      backpropagation algorithm in a computer simulation of ODT of weakly inhomogeneous
      cylindrical objects being interrogated in a limited number of scattering
      experiments employing incident plane waves. Our study has potential applications
      in biomedical imaging and tomographic microscopy.

PMID- 16302388
TI  - Convex approximation to the likelihood criterion for aperture synthesis imaging.
AB  - Aperture synthesis allows one to measure visibilities at very high resolutions by
      coupling telescopes of reasonable diameters. We consider the case where
      visibility amplitudes and phase are measured separately. It leads to an
      estimation problem where the noise model yields a nonconvex data-likelihood
      criterion. We show how to optimally approximate the noise model while keeping the
      criterion convex. This approximation has been validated both on simulations and
      on experimental data.

PMID- 16302389
TI  - Defocus morphing in real aperture images.
AB  - A new concept called defocus morphing in real aperture images is introduced. View
      morphing is an existing example of shape-preserving image morphing based on the
      motion cue. It is proved that images can also be morphed based on the depth
      related defocus cue. This illustrates that the morphing operation is not
      necessarily a geometric process alone; one can also perform a photometry-based
      morphing wherein the shape information is implicitly buried in the image
      intensity field. A theoretical understanding of the defocus morphing process is
      presented. It is shown mathematically that, given two observations of a three
      dimensional scene for different camera parameter settings, we can obtain a
      virtual observation for any camera parameter setting through a simple nonlinear
      combination of these observations.

PMID- 16302390
TI  - Light diffraction by a three-dimensional object: differential theory.
AB  - The differential theory of diffraction of light by an arbitrary object described
      in spherical coordinates is developed. Expanding the fields on the basis of
      vector spherical harmonics, we reduce the Maxwell equations to an infinite first
      order differential set. In view of the truncation required for numerical
      integration, correct factorization rules are derived to express the components of
      D in terms of the components of E, a process that extends the fast Fourier
      factorization to the basis of vector spherical harmonics. Numerical overflows and
      instabilities are avoided through the use of the S-matrix propagation algorithm
      for carrying out the numerical integration. The method can analyze any shape
      and/or material, dielectric or conducting. It is particularly simple when applied
      to rotationally symmetric objects.

PMID- 16302391
TI  - Fast iterative, coupled-integral-equation technique for inhomogeneous profiled
      and periodic slabs.
AB  - A fast coupled-integral-equation (CIE) technique is developed to compute the
      plane-TE-wave scattering by a wide class of periodic 2D inhomogeneous structures
      with curvilinear boundaries, which includes finite-thickness relief and rod
      gratings made of homogeneous material as special cases. The CIEs in the spectral
      domain are derived from the standard volume electric field integral equation. The
      kernel of the CIEs is of Picard type and offers therefore the possibility of
      deriving recursions, which allow the computation of the convolution integrals
      occurring in the CIEs with linear amounts of arithmetic complexity and memory. To
      utilize this advantage, the CIEs are solved iteratively. We apply the biconjugate
      gradient stabilized method. To make the iterative solution process faster, an
      efficient preconditioning operator (PO) is proposed that is based on a formal
      analytical inversion of the CIEs. The application of the PO also takes only
      linear complexity and memory. Numerical studies are carried out to demonstrate
      the potential and flexibility of the CIE technique proposed. Though the best
      efficiency and accuracy are observed at either low permittivity contrast or high
      conductivity, the technique can be used in a wide range of variation of material
      parameters of the structures including when they contain components made of both
      dielectrics with high permittivity and typical metals.

PMID- 16302392
TI  - Statistical properties of light reflected and transmitted by a thick horizontally
      inhomogeneous turbid layer.
AB  - The paper is devoted to the introduction of simple analytical relationships
      between statistical distributions of various radiative transfer characteristics
      for an inhomogeneous turbid layer with the extinction coefficient varying in the
      horizontal direction. Results are valid for an optically thick light-scattering
      layer having arbitrary local scattering laws and single-scattering albedos. It is
      shown that the statistical distribution of the optical thickness can be obtained
      directly from the measured statistical distribution of the reflectance or
      transmittance of a horizontally inhomogeneous light-scattering layer.

PMID- 16302393
TI  - Calculation of emittance of a coating layer with the Kubelka-Munk theory and the
      Mie-scattering model.
AB  - The radiative transfer equation in a coating layer with a not too high
      concentration of pigment particles, which is attached to a substrate, is resolved
      in terms of Kubelka-Munk theory and a Mie-scattering model. In the case of a
      coating layer constituted with aluminum spherical particles, the dependence of
      emittance of the coating layer on particle radius and thickness of the layer are
      studied. The optimum radius of a pigment particle is suggested as well.

PMID- 16302394
TI  - Scattering, absorption, and extinction by thin fibers.
AB  - For electromagnetic wave incidence on a thin fiber at an angle theta i with the
      fiber axis, induced currents are described by linear combinations of driven and
      traveling waves exp(+/-ikz cos theta i) and exp(+/-imkz), where the complex
      factor m serves to remove singularities in the normalizing constants of the
      currents. The fiber may be solid, hollow, or coated, with quite general
      constitutive parameters. Results are given for scattering, absorption,
      extinction, and radar cross sections, using energy conservation and reciprocity
      as consistency checks, and compared with independent computations, including the
      Born approximation for tenuous conductors and dielectrics. In addition, the far
      field amplitude of a 50 wavelength conductor is obtained and compared with the
      well-known long-wire approximation.

PMID- 16302395
TI  - Detailed analytical approach to the Gaussian surface bidirectional reflectance
      distribution function specular component applied to the sea surface.
AB  - A statistical sea surface specular BRDF (bidirectional reflectance distribution
      function) model is developed that includes mutual shadowing by waves, wave facet
      hiding, and projection weighting. The integral form of the model is reduced to an
      analytical form by making minor and justifiable approximations. The new form of
      the BRDF thus allows one to compute sea reflected radiance more than 100 times
      faster than the traditional numerical solutions. The repercussions of the
      approximations used in the model are discussed. Using the analytical form of the
      BRDF, an analytical approximation is also obtained for the reflected sun radiance
      that is always good to within 1% of the numerical solution for sun elevations of
      more than 10 degrees above the horizon. The model is validated against measured
      sea radiances found in the literature and is shown to be in very good agreement.

PMID- 16302396
TI  - Geometrical theory of aberrations near the axis in classical off-axis reflecting
      telescopes.
AB  - A geometrical theory of aberrations for the vicinity of the focus of arbitrary
      off-axis sections of conic mirrors is derived. It is shown that an off-axis conic
      mirror introduces linear astigmatism in the image. However, in classical two
      mirror telescopes this aberration can be eliminated by tilting the secondary
      parent mirror axis. It is also shown that the practical geometrical-optics
      performance of a classical off-axis two-mirror telescope with no linear
      astigmatism is equivalent to the performance of an on-axis system, proving that
      both systems have identical third-order coma. To demonstrate the applicability of
      the theory developed in a practical system, a fast (i.e., f/2), compact,
      obstruction-free classical off-axis Cassegrain telescope is designed.

PMID- 16302397
TI  - Theory of "frozen waves": modeling the shape of stationary wave fields.
AB  - In this work, starting by suitable superpositions of equal-frequency Bessel
      beams, we develop a theoretical and experimental methodology to obtain localized
      stationary wave fields (with high transverse localization) whose longitudinal
      intensity pattern can approximately assume any desired shape within a chosen
      interval 0 < or = z < or = L of the propagation axis z. Their intensity envelope
      remains static, i.e., with velocity v = 0, so we have named "frozen waves" (FWs)
      these new solutions to the wave equations (and, in particular, to the Maxwell
      equation). Inside the envelope of a FW, only the carrier wave propagates. The
      longitudinal shape, within the interval 0 < or = z < or = L, can be chosen in
      such a way that no nonnegligible field exists outside the predetermined region
      (consisting, e.g., in one or more high-intensity peaks). Our solutions are
      notable also for the different and interesting applications they can have-
      especially in electromagnetism and acoustics--such as optical tweezers, atom
      guides, optical or acoustic bistouries, and various important medical
      apparatuses.

PMID- 16302398
TI  - Analysis of reentrant two-mirror nonplanar ring laser cavity.
AB  - A rigorous analysis is performed on the reentrant nonplanar ring laser cavity
      constructed by a Herriott-type multipass cell. Since the cavity is highly
      nonplanar, the angle between the incident planes at each reflection becomes
      different from that of the image rotation angles. The beam rotation, astigmatism,
      and spherical aberration are considered to obtain a self-consistent solution of
      the Gaussian beam. It turns out that spherical aberration is an important issue
      for this nonplanar resonator. Without taking into account the spherical
      aberration, a stable resonator would be difficult to realize. Using a self
      consistent Gaussian beam propagation method, the laser beam characteristics are
      solved analytically. The results are compared with that of the 2 x 2 ABCD method.

PMID- 16302399
TI  - Dihedral representations and statistical geometric optics. I. Spherocylindrical
      lenses.
AB  - The linear 2-dim irreducible representations of the dihedral groups (Dn) are
      interpreted as classical linear operators of geometrical optics. It is shown that
      the 2-dim irreducible representation of D4 is simply the refractive group
      described by Campbell [Optom. Vision Sci. 74, 381 (1997)]. The dihedral Fourier
      inverse mechanism is introduced and shown to provide a systematic connection
      between the standard refractive data and their vector space representation, as
      proposed by Thibos et al. [Vision Sci. Appl. 2, 14 (1994)].

PMID- 16302400
TI  - Spectrum of an optical resonator with spherical aberration.
AB  - By using an operator description we derive the spectrum of a symmetric two-mirror
      resonator in the presence of spherical aberration.

PMID- 16302401
TI  - Spatial phase-shift interferometry--a wavefront analysis technique for three
      dimensional topometry.
AB  - We describe a new wavefront analysis method, in which certain wavefront
      manipulations are applied to a spatially defined area in a certain plane along
      the optical axis. These manipulations replace the reference-beam phase shifting
      of existing methods, making this method a spatial phase-shift interferometry
      method. We demonstrate the system's dependence on a defined spatial Airy number,
      which is the ratio of the characteristic dimension of the manipulated area and
      the Airy disk diameter of the optical system. We analytically obtain the
      resulting intensity data of the optical setup and develop various methods to
      accurately reconstruct the inspected wavefront out of the data. These
      reconstructions largely involve global techniques, in which the entire
      wavefront's pattern affects the reconstruction of the wavefront in any given
      position. The method's noise sensitivity is analyzed, and actual reconstruction
      results are presented.

PMID- 16302402
TI  - High-efficiency, liquid-crystal-based, controllable diffraction grating.
AB  - We propose a new reflective liquid-crystal diffraction grating design attained by
      combining the use of a polymer wall to reduce the detrimental effect of the
      fringing electric field in a high-resolution grating and a quarter-wave plate to
      make the device polarization independent. This design could offer significant
      performance advantages in a projection display system. Results of calculations
      are compared with experimental data.

PMID- 16302403
TI  - Eigenvalue and field equations of three-layered uniaxial fibers and their
      applications to the characteristics of long-period fiber gratings with applied
      axial strain.
AB  - By using the Debye potentials, the exact eigenvalue equations and the
      corresponding field distributions of the core and cladding modes for three
      layered, radially stratified, and dielectric uniaxial optical fibers are derived
      completely; the modes include TE, TM, and hybrid HE/EH modes. The strain
      characteristics of long-period fiber gratings' (LPFGs') with applied axial strain
      are investigated theoretically by studying three-layered uniaxial optical fibers.
      When uniform axial strain is applied to fiber, the core, and inner and outer
      cladding become uniaxial crystal optically; that is, the optical axes are
      parallel to the fiber's axis. Analytic expressions of the strain sensitivities of
      LPFGs are derived. The analysis reveals that the strain sensitivities of LPFGs
      based on various cladding modes, including the shift value and direction of the
      resonance wavelength, differ greatly.

PMID- 16302404
TI  - On the wavefront spacing of focused, radially polarized beams.
AB  - We analyze the phase behavior of strongly focused, radially polarized
      electromagnetic fields. It is shown that, under certain circumstances, the
      spacing between successive wavefronts can be either greater or smaller than that
      of a plane wave of the same frequency. Also, this spacing can be significantly
      larger than that which is predicted for a linearly polarized field that is
      focused by the same system.

PMID- 16302405
TI  - Cramer-Rao lower bounds on the estimation of the degree of polarization in
      coherent imaging systems.
AB  - We analyze the estimation precision of the parameter of the orthogonal state
      contrast image (OSCI) under coherent illumination. This parameter represents the
      degree of polarization of the light if the materials that compose the scene are
      purely depolarizing. Two different estimation modes are considered, depending on
      the uniformity of the illumination of the scene. We first determine lower bounds
      on the estimation precision in both cases by computing the Cramer-Rao lower
      bounds (CRLBs) for unbiased estimation. This allows us to compare the potential
      precision that can be reached in each mode. We then consider the estimators based
      on empirical averaging of the data, and we show that there are cases where they
      are strongly biased. We thus propose and characterize another estimator based on
      the natural representation of the OSCI, which is asymptotically unbiased and
      whose variance is close to the unbiased CRLB.

PMID- 16302406
TI  - Vector propagation of radially polarized Gaussian beams diffracted by an axicon.
AB  - On the basis of the vectorial Rayleigh diffraction integrals and stationary-phase
      method, the analytic expression describing the vectorial field distribution of
      radially polarized Gaussian beams diffracted by an axicon is derived. The
      theoretical analysis and simulation calculation show that the radial component of
      the diffraction field is the propagation-invariant first-order Bessel beam when
      the radially polarized Gaussian beam illuminates the axicon. However, the
      longitudinal component possesses no such behavior because of its intrinsic r
      dependence, and its central intensity is the maximum. The longitudinal component
      is related to the open angle and index of the axicon, which has to be considered
      when the open angle and index are large. For a small open angle and index, the
      longitudinal component can be neglected, and the scalar approximation is valid.

PMID- 16302407
TI  - Coherence and polarization properties of far fields generated by quasi
      homogeneous planar electromagnetic sources.
AB  - In studies of radiation from partially coherent sources the so-called quasi
      homogeneous (QH) model sources have been very useful, for instance in elucidating
      the behavior of fields produced by thermal sources. The analysis of the fields
      generated by such sources has, however, been largely carried out in the framework
      of scalar wave theory. In this paper we generalize the concept of the QH source
      to the domain of the electromagnetic theory, and we derive expressions for the
      elements of the cross-spectral density matrix, for the spectral density, the
      spectral degree of coherence, the degree of polarization, and the Stokes
      parameters of the far field generated by planar QH sources of uniform states of
      polarization. We then derive reciprocity relations analogous to those familiar in
      connection with the QH scalar sources. We illustrate the results by determining
      the properties of the far field produced by transmission of an electromagnetic
      beam through a system of spatial light modulators.

PMID- 16302408
TI  - Angular dependence of the reflectance from an isotropic polydomain medium: the
      influence of absorption.
AB  - The angular dependence of the reflectance from an absorbing randomly oriented
      polydomain medium consisting of domains either small or large compared with the
      wavelength is investigated. Besides the two conventional cases, where the
      refractive index of the incidence medium is either smaller or larger than the
      averaged index of refraction (small-domain limit) or every principal index of
      refraction of the domains (large-domain limit), we also discuss a third principal
      case, which exists only in the large-domain limit. In this third case, only one
      of the principal indices of refraction is larger than that of the incidence
      medium, while the averaged index of refraction is smaller. Thus, in contrast to
      the small-domain limit, total reflection is completely suppressed even in the
      absence of absorption. A characteristic property of such a polydomain medium is
      its ability to considerably depolarize linear polarized light in spite of being
      optically isotropic. Additionally, the parallel polarized reflectance Rp can
      exceed the perpendicular polarized reflectance Rs over certain angle of incidence
      ranges. Absorption decreases these domain-size-dependent properties, even under
      the assumption of constant anisotropy. Nevertheless, for materials with low
      absorption indices, these effects can affect the optical properties
      significantly.

PMID- 16302409
TI  - Surface plasmon photonic bandgap in azopolymer gratings sputtered with gold.
AB  - Surface plasmons (SPs) are generated on a doubly corrugated gold-covered surface.
      The corrugations were obtained by direct holographic inscription of surface
      relief gratings on an azopolymer film. This method permits the superposition of
      multiple surface profiles with easy control of the grating spacing. One grating
      is inscribed to act as coupler for the incident light to the SP and a second
      grating is inscribed to generate a gap in the SP dispersion curve. The coupling
      and the gap can be observed by measuring the reflectivity of the gold surface as
      a function of the angle of incidence and the wavelength of the probe beam.

PMID- 16302410
TI  - Application of the fractional Fourier transformation to digital holography
      recorded by an elliptical, astigmatic Gaussian beam.
AB  - The authors have studied the diffraction pattern produced by a particle field
      illuminated by an elliptic and astigmatic Gaussian beam. They demonstrate that
      the bidimensional fractional Fourier transformation is a mathematically suitable
      tool to analyse the diffraction pattern generated not only by a collimated plane
      wave [J. Opt. Soc. Am A 19, 1537 (2002)], but also by an elliptic and astigmatic
      Gaussian beam when two different fractional orders are considered. Simulations
      and experimental results are presented.

PMID- 16302411
TI  - [Whether sick or healthy -- the life style decides. Down from the couch!].

PMID- 16302412
TI  - [Typical autumn poisoning. trouble when the pumpkin tastes bitter].

PMID- 16302413
TI  - [MMW- Drug Prize 2005 for simvastatin/ezetimib (Inegy). LDL goal values are
      easier to reach now].

PMID- 16302414
TI  - [Natural substances and pharmaceutical preparations can prevent cancer.
      Chemoprevention instead of chemotherapy].

PMID- 16302415
TI  - [Are you prepared for avian flu?].

PMID- 16302416
TI  - [Treatment of ovarian cancer--an update].

PMID- 16302417
TI  - [Sonography of malignant ovarian tumors].
AB  - For the diagnosis and differential diagnosis of malignant tumors of the ovaries,
      transvaginal ultrasound is currently the preferred method. Ultrasound is
      indispensable for the pre-operative assessment of the biological significance of
      an ovarian tumor. With its aid,the indication for a surgical procedure can be
      established with a high degree of sensitivity and specificity and, where
      appropriate, the therapeutic approach definitively established. A further
      important application is screening for the early detection of an ovarian cancer.
      Although a high level of sensitivity and specificity can also be achieved for
      such an indication, an otherwise desirable screening procedure--at least in high
      risk groups and post-menopausal women--is nevertheless controversial on account
      of the low prevalence of ovarian carcinoma and the associated poor positive
      predictive value (PPV).

PMID- 16302418
TI  - [Surgical treatment of ovarian cancer].
AB  - Surgical Treatment of Ovarian Cancer Primary radical surgery of ovarian carcinoma
      determines the further course of the disease, and thus also the outcome of the
      patient. Postoperative residual tumor is one of the most important prognostic
      factors. The overriding aim is complete removal of the tumor. A high level of
      surgical expertise, an interdisciplinary team and optimal postoperative intensive
      care are indispensable prerequisites for the best possible surgical treatment of
      ovarian carcinoma. Neither chemotherapy nor any other measures are capable of
      rescuing a suboptimal postoperative situation.

PMID- 16302419
TI  - [Pharmacotherapy in ovarian carcinoma].
AB  - Pharmacotherapy in Ovarian Carcinoma Although recent years have seen considerable
      progress in the treatment of primary and recurrent ovarian carcinoma, the
      mortality rate continues to be very high. Possibilities for improvement include
      compliance with the current treatment recommendations both in the surgical and
      medical areas, as well as the participation in clinical studies or treatment in
      study centers.

PMID- 16302420
TI  - [Acquired effluvium of head hair: common conditions in women].
AB  - Acquired disorders of hair growth in women may present clinically either as
      effluvium or alopecia. The relevant pathologies include androgenetic alopecia,
      postpartum effluvium, tinea capitis, trichotillomania and alopecia areata.

PMID- 16302421
TI  - [Efficacy and safety of treatment of erectile dysfunction with Vardenafil under
      routine conditions].

PMID- 16302422
TI  - [Cardiovascular protection in diabetic patients with heart disease in the
      doctor's office].
AB  - The long-term care of diabetic patients with heart disease poses a particular
      challenge. Various combinations of risk factors, progression of the coronary
      heart disease, and complications with further organic damage by the underlying
      diabetes, frequently necessitate a differentiated diagnostic work-up and
      management. This can be implemented only by close cooperation between the various
      specialities. Structured processes may be useful provided they are correctly
      applied and implemented. Guideline-based treatment of detected cardiovascular
      risk factors can improve quality of life, reduce morbidity and cardiovascular
      mortality and thus save costs over the long term.

PMID- 16302423
TI  - [Physicians more often accused of false information. Do I have to inform minors,
      too?].

PMID- 16302424
TI  - [When the envy poisons practice climate: against discontent, envy and conflicts
      in practice team there are some remedies].

PMID- 16302425
TI  - [Ray of hope for therapy of severe allergic asthma: blockade of IgE closes the
      treatment gap].

PMID- 16302426
TI  - [Highly concentrated omega-3-fatty acids. A new means in the secondary
      prevention].

PMID- 16302427
TI  - [Long-chain omega-3 fatty acids: highly concentrated only as ethyl ester].

PMID- 16302428
TI  - [Patient complains about sleep disorders: place "restless legs" therein].

PMID- 16302429
TI  - [Palm phlegmon. There is treatment need].

PMID- 16302430
TI  - Too much information; not enough wisdom.

PMID- 16302431
TI  - Health-related issues on the agenda.

PMID- 16302432
TI  - Outsourcing: friend or foe.
AB  - With rising costs and tight controls on reimbursement, physicians need to dig
      deeper into expenses and find ways to reduce costs while tapping into an equal or
      higher level of expertise. Outsourcing offers an attractive solution. This
      article identifies the areas where outsourcing is most valuable and effective,
      and provides some methodologies for achieving a successful result.

PMID- 16302433
TI  - Performance evaluation, part 3: Communicating with employees in the evaluation
      process.
AB  - In the first of three articles (MPM 2005; Vol. 20 #5: 229-232), the author
      reviewed the broad concept of performance evaluation, defined the term validity
      in the evaluation process as a standard derived from court decisions, and
      detailed objective criteria that managers should follow in rating employees. The
      second article (MPM 2005; Vol. 21 #1: 21-26) stressed the development of
      standards, cited examples applicable to daily practice, and detailed errors that
      are commonly made in rating personnel. This last article covers the very
      important topic of communicating the results of performance evaluation with
      employees.

PMID- 16302434
TI  - Myriad pieces of facility development, part 1.
AB  - Medical practices often find that they have outgrown their office space and
      cannot relocate within the same building or in the vicinity of their current
      location. They are confronted with the need and desire to develop and build a new
      facility. Part 1 of this article discusses a plausible strategy to this intricate
      task. The central concept is to use a team approach by calling on specialists to
      accomplish certain functions. Although this process may seem complex and
      expensive, it is likely to provide significant value. This value may express
      itself not only in greater efficiency of the practice as a result of rational
      planning of the space, but also in the intrinsic worth of the facility as a real
      estate investment.

PMID- 16302436
TI  - Silent PPOs: the stealth discounting of provider reimbursement.
AB  - Physicians are losing millions of dollars per year from payers engaging in
      abusive discounting practices. One of the worst of these practices is the silent
      PPO. This article explains what a silent PPO is and how it unlawfully reduces a
      provider's reimbursement. The article discusses how providers can recognize
      silent PPOs and how to protect their practices from this discounting. The article
      also reviews statutes that prohibit or regulate silent PPOs and recent court
      decisions finding in favor of providers and against silent PPOs.

PMID- 16302437
TI  - Introduction to group medical appointments.
AB  - Both patients and providers suffer from time constraints that limit their face-to
      face time. With increasing limitations in reimbursement, office (and hospital)
      visits tend to become more condensed. This leads to dissatisfied patients and
      unfulfilled providers. In an effort to remedy this situation, many practices have
      adopted group medical appointments. This article outlines the; concept,
      mechanics, responsibilities of the parties, and the reimbursementfeatures of this
      relatively novel and seemingly paradoxical initiative.

PMID- 16302435
TI  - Improving the bottom line through a better understanding of rules and statutes.
AB  - In an effort to improve their incomes, providers are often deterred from
      undertaking certain initiatives that they have heard to be illegal under various
      statutes or contracts. Though the statutes do limit joint ventures, certain
      referrals, and other practices, some of these beliefs are based on
      misinterpretations or "myths. " In reality, practitioners may have more
      flexibility than they assume. This article discusses some of the matters that
      confront practitioners in regard to Stark laws, anti-kickback regulations, and
      other statutes when they consider contractual arrangements with various sources
      of services for their patients. The authors explain why clinicians may have more
      recourse than they estimate in appealing Medicare reimbursement rulings.

PMID- 16302438
TI  - Tax planning in the wake of the new tax shelter regulations.

PMID- 16302439
TI  - Don't lose your home in a lawsuit...or waste the equity.
AB  - Like most of us, a physician's home constitutes a major asset. Under normal
      circumstances, it is subject to attachment by creditors in a malpractice judgment
      or in any other litigation settlement that may exceed the limits of insurance
      coverage. This article describes the author's view of substandard options to
      shield a home from creditors. While some of these techniques have validity for
      certain planning purposes, they do not provide the optimal protection that
      physicians may desire. The author then proposes strategies that may be suitable
      for many individuals.

PMID- 16302440
TI  - The electronic medical record: a valuable partner.
AB  - Clinical technology within the U.S. healthcare system is among the most advanced
      in the world. Basic administrative capabilities are lagging, however. Lack of
      standardization affecting the ability to integrate diverse systems and the
      prohibitive costs associated with acquisition and implementation are two major
      obstacles to improving administrative capacities. This article describes the
      basics of electronic medical records (EMR) implementation failures and successes
      and the evolution of the electronic health record (EHR) as part of the future of
      healthcare IT and continuity of care.

PMID- 16302441
TI  - Hospitals under attack.
AB  - This article presents an overview of recent cases brought by plaintiffs all over
      the nation against nonprofit hospitals and their charity care practices. The
      article focuses on Illinois law and the context of these cases and provides a
      background for the impetus of this influx of charitable care lawsuits.

PMID- 16302442
TI  - Ongoing concerns.

PMID- 16302443
TI  - Reviewing staff performance and salaries.
AB  - Do you feel like you're on shaky ground when it comes time to evaluate your
      staffs performance or to give them raises? If so, you're not alone. Staff
      performance and salary reviews are among the most dreaded tasks among medical
      practice managers. Yet, they are among the most effective techniques you can use
      to motivate, manage, correct, and reward your staff. This article provides an
      overview of the different kinds of appraisals you will need to conduct with your
      staff and the order in which to do them. It suggests that you begin the process
      by establishing concrete goals for your medical practice and then help your staff
      follow suit by developing their own performance goals for the next six months.
      This article also provides how-to guidance about conducting regular interim
      progress reviews with your staff to keep abreast of progress, changes, and
      problems and to issue ongoing assistance and feedback. It explains how to conduct
      tension-free semi-annual staff performance reviews and semi-annual or annual
      salary reviews, including a formula for calculating potential raises for each
      employee in nine increments. Finally, this article offers additional tips for
      evaluating your staffs performance, including job description updates and staff
      surveys.

PMID- 16302444
TI  - Coding for asthma patient education in the primary care setting.
AB  - Counseling and education for chronic diseases is a common service provided by
      primary care physicians. By not using and understanding the basic concepts in
      documentation and coding, primary care providers deny themselves proper
      reimbursement for the quality care they provide. Although we have used asthma as
      an example, concepts discussed here can be applied to other chronic diseases that
      require patient self-management. We review coding strategies that should be used
      when counseling and education are the main focus of the patient visit. We review
      additional procedures and techniques to make office flow, documentation, and
      coding proceed more smoothly.

PMID- 16302445
TI  - Trends in the consumer price index.

PMID- 16302446
TI  - Canine transposition.
AB  - Transposition is described as an interchange in the position of two teeth within
      the same quadrant of the dental arch. Canine transposition is reportedly the most
      common transposition in human dentition. The incidence of maxillary canine
      premolar transposition is reported to be 0.135-0.510%. Although the exact
      mechanism of canine transposition is unclear, it seems to be closely related to
      genetically influenced, retained deciduous canine, and a history of trauma. In
      this article, we focus on the classification, incidence, etiology, and treatment
      modalities of tooth transposition. We hope this information will help clinicians
      treating patients with this kind of dental anomaly.

PMID- 16302447
TI  - Determination of the minmum effective dosages of praziquantel, albendazole, and
      mebendazole against Clonorchis sinensis infection in rats.
AB  - In order to determine the minimum effective dosages of praziquantel, albendazole,
      and mebendazole against Clonorchis sinensis infection in Sprague-Dawley rats,
      each rat was infected with 30 metacercariae and treated with one of three drugs.
      The rats were killed and examined 25 days after praziquantel treatment or 11 days
      after albendazole or mebendazole treatment. The minimum effective dosages were a
      single dose of praziquantel 375 mg/kg, albendazole 150 mg/kg, and mebendazole 150
      mg/kg. Trials are required to determine whether these dosages are useful in the
      treatment of human clonorchiasis.

PMID- 16302448
TI  - Cerebral radionecrosis in patients with nasopharyngeal carcinoma.
AB  - This study involved seven patients with cerebral radionecrosis following
      radiation therapy for nasopharyngeal carcinoma (NPC). Their charts were reviewed
      and the relationship of extracranial malignancies to cerebral radionecrosis was
      investigated. The radiation dose ranged from 70 to 135 Gy, and the latency was
      from 6 to 39 months. Two of seven patients died of NPC-related complications
      during follow-up. The crude incidence of cerebral radionecrosis in patients with
      NPC was 0.93% in our series. Improvement of symptoms could be achieved by
      corticosteroid therapy, with or without surgery. In a review of the literature,
      there were 306 cases of cerebral radionecrosis in extracranial malignancies. The
      nasopharynx is the most common primary site in cerebral radionecrosis of
      extracranial malignancies, followed by the scalp and sinonasal tract. The 3-year
      overall survival rate in our series was 68.57%, as provided by the Kaplan-Meier
      product limited method. Cerebral radionecrosis in NPC patients should be
      differentiated from tumor recurrence, in order to apply the appropriate
      treatment.

PMID- 16302449
TI  - Effects of total coronary artery occlusion on vascular endothieial growth factor
      and transforming growth factor beta.
AB  - Vascular endothelial growth factor (VEGF) and transforming growth factor beta
      (TGF-beta1) play an important role in angiogenesis. We wanted to determine if
      concentrations of growth factors in the coronary sinus (CS) and right atrium (RA)
      are higher in coronary artery disease patients with total occlusions than in
      those with partial occlusions. Fifty-one patients scheduled for coronary artery
      angiography were evaluated for possible recruitment. A 6F Goodale-Lubin catheter
      was used to collect blood from the CS and RA. Data for all but four patients were
      gathered successfully, leaving 47 study patients. The reviewer was blinded to
      growth factor data when interpreting coronary angiographic findings. Of the 47
      enrolled patients, 32 had at least one diseased vessel, seven of whom had at
      least one major total epicardial coronary occlusion. In all 32 patients, the
      concentrations of VEGF in the CS were higher than those in the RA (31.5 +/- 2.7
      vs 27.1 +/- 1.8 pg/mL; p = 0.005). Patients with total occlusions had higher VEGF
      concentrations in the CS than those with non-total occlusions (38.9 +/- 8.0 vs
      29.5 +/- 2.6 pg/mL; p = 0.037). The differences in TGF-beta1 in the two groups
      were not statistically significant. The higher CS VEGF concentrations in patients
      with total occlusion indicate that VEGF may play a part in the development of
      angiogenesis.

PMID- 16302450
TI  - Noninfectious hypopion after intravitreal triamcinolone acetonide injection for
      central retinal vein occlusion: a case report.
AB  - Although it is rare, infectious endophthalmitis is a severe ocular complication
      resulting from intravitreal injection of triamcinolone acetonide (TA). Therefore,
      care must be taken by ophthalmologists to differentiate between what is
      infectious and noninfectious endophthalmitis. We report on a 62-year-old woman
      who received an intravitreal injection of TA for treatment of central retinal
      vein occlusion. One day after the injection, a hypopion (a white-yellowish
      deposit) was noted in the inferior anterior chamber. The patient complained that
      her vision had deteriorated, but there was no pain, eyelid edema, increased
      conjunctival injection or corneal edema. The hypopion gradually diminished and by
      the fifth postoperative day, resolved completely without the administration of
      intravitreal or systemic antibiotic therapy.

PMID- 16302451
TI  - HCV infection complicated with nephrotic syndrome, immune complex crescentic
      glomerulonephritis and acute renal failure: a case report.
AB  - There is ample evidence suggesting that hepatitis C virus (HCV)-associated
      autoimmunity plays a role in a broad spectrum of autoimmune diseases, which are
      usually overlooked. We report on a case of nephrotic syndrome, palpable purpura,
      cryoglobulinemia, hypocomplementemia, and acute renal failure complicated by
      immune complex glomerulonephritis (GN). The patient is a 64-year-old man with HCV
      infection, who was initially considered to present only an HCV-associated
      cryoglobulinemic GN. However, renal biopsy revealed a "full house" immune complex
      crescentic GN, which led to our subsequent investigation. The attending
      clinicians faced what is a common dilemma, where an HCV-associated autoimmune
      disease inevitably switches to a lupus-like GN. Hence, we also discuss treatment.

PMID- 16302452
TI  - Concurrent extravasation mucocele and epidermoid cyst of the lower lip: a case
      report.
AB  - An uncommon case of concurrent extravasation mucocele and epidermoid cyst in the
      lower lip of a 13-year-old boy is described. To our knowledge, there is no other
      report of such a concurrence, neither at the same site nor at different
      locations, involving these two lesions in the oral mucosa.

PMID- 16302453
TI  - Basal cell carcinoma of the nipple-areola complex: a case report.
AB  - Basal cell carcinoma (BCC) of the nipple-areola complex is very rare. Only 24
      cases were reported in the literature and 17 (70.8%) of these cases arose in men.
      Most of the cases were treated with simple excision. We report on a case of BCC
      of the nipple-areola complex in a 46-year-old woman, treated with partial
      mastectomy. Metastasis to the axillary lymph nodes had been noted in 3 (12.5%) of
      the 24 reported cases of BCC of the nipple-areola complex. Thus, we applied the
      concept of the sentinel lymph node to detect possible metastases of axillary
      lymph nodes, letting us avoid the unnecessary axillary lymph node dissection and
      possible future morbidity.

PMID- 16302454
TI  - Spontaneous fractures and root resorption in 3rd. molars of Wistar rats.

PMID- 16302455
TI  - Effect of a chlorhexidine varnish on Streptococcus mutans in saliva.
AB  - The aim of the present work was to evaluate the effect of a thymol/chlorhexidine
      varnish at 1% on Streptococcus mutans (S. mutans) in saliva applied after
      teaching and evaluating an oral hygiene technique and dressing the cavities to
      reduce the bacterial load. Streptococcus mutans levels in saliva samples and
      dental status were evaluated in 38 girls between 6 and 13 years of age with high
      risk of caries. The girls were then trained and assessed in oral hygiene. On day
      seven, oral hygiene assessment was repeated and supragingival plaque control was
      performed. After 15 days (day 21) another culture was performed and the level of
      S. mutans in saliva samples was determined. Evaluation and reinforcement of the
      oral hygiene technique were repeated and the cavities were dressed to reduce the
      bacterial load. At 36 days from the onset of the experiment, culture S. mutans
      counts were performed; evaluation and reinforcement of the oral hygiene technique
      were undertaken and the girls were divided randomly into two groups: 1 The teeth
      of the experimental group were painted with a varnish containing 1% chlorhexidine
      and thymol. 2 The teeth of the control group were painted with a placebo varnish
      containing only thymol. After a further 15 days (day 51), another culture and S.
      mutans counts were performed. The results showed a gradual reduction in the S.
      mutans counts in saliva in each subsequent experimental period analyzed.
      Significant differences between the experimental group and the control group were
      recorded after treatment. It can be concluded that the levels of S. mutans
      decreased in each subsequent experimental period and that the application of a 1%
      chlorhexidine varnish elicited a significant reduction in S. mutans levels.

PMID- 16302456
TI  - Transportation of curved canals instrumented with manual and mechanical
      techniques.
AB  - The purpose of this study was to compare the effect of manual and mechanical
      instrumentation techniques in curved root canals using area of dentine removed
      and canal axis movement as the end-points. Sixty mandibular molars with curved
      root canals with angulations ranging from 15 degrees to 45 degrees were selected.
      The teeth were embedded in transparent resin in a grilon key-like muffle using
      Bramante's procedure. The roots were horizontally sectioned at three levels and
      pre and post instrumentation photographs were taken. The sections were
      reassembled in the muffle and the canals were instrumented with manual and
      mechanical techniques using Cursor (W&H). Anatomic measurements of transportation
      were made employing pre and post instrumentation photographs and Macintosh Image
      1.45 Software. Statistical analysis of the data was performed by ANOVA. There
      were no significant differences in canal center axis movement among the groups.
      Differences in area of dentine removed between manual and mechanical
      instrumentation techniques were observed at the apical level only.

PMID- 16302457
TI  - Shaping of curved root canals instrumented with stainless steel and nickel
      titanium files.
AB  - The cleaning efficiency and the quality of the surgical preparation is mainly
      conditioned by root canal anatomy, the instruments and the technique employed.
      The purpose of the present study was to evaluate the extent of straightening of
      curved root canals and the changes in endodontic anatomy caused by the use of
      Flex-R, Onyx-R and Nitiflex files with the balanced forces technique. Sixty
      mandibular molars were selected for evaluation of angulation and transportation.
      Pre and post instrumentation radiographs were taken of the mesiodistal and
      buccolingual aspects of each tooth. The radiographs were projected on a
      transparent sheet, the contours of each tooth and file were outlined and the
      canal curvature was measured. Pre and post instrumentation tracings were overlaid
      and the extent of transportation was measured with a micrometric caliper.
      Statistical analysis of the data was performed employing Student's "t" test,
      Analysis of Variance and Bonferroni's test. The results showed that all the
      instruments reduced canal curvature significantly. Transportation in the
      mesiodistal direction did not reach statistical significance whereas
      transportation in the buccolingual direction was statistically significant.

PMID- 16302458
TI  - Analysis of the epidemiological features of oral cancer in the city of Buenos
      Aires.
AB  - Oral cancer comprises 0.6 to 5% of all human malignant tumors. It is accepted in
      the literature that the clinical evolution of oral cancer has a bad prognosis,
      i.e. the five year survival rate ranges from 34% to 56%. The aim of the present
      study was to present a metaanalysis of the most relevant publications on oral
      cancer in the city of Buenos Aires, including our own series. The publications
      reviewed herein include the following series: 517 cases (1950-1970), 243 cases
      (1961-1968), 336 cases (1972-1984), and 274 cases (1992-2000). The clinical end
      points evaluated were: age, distribution by sex, tumor site, presence of
      metastatic adenopathies, and clinical stage. A comparative statistical evaluation
      of the clinical parameters assessed was performed. Survival was evaluated by the
      test of Kaplan-Meier. The male/female ratio was 7.1:1 for the 1950-1970 period,
      4.3:1 for the 1961-1968 period; 2.3:1 for the 1972-1984 period; and 1.24:1 in our
      series (1992-2000). The most frequent tumor site (21 to 35% of the cases) was the
      tongue. At the time of diagnosis, 60-71% of the patients had advanced TNM
      clinical stages (III and IV). Our follow-up revealed a five-year survival rate
      after diagnosis of 39%. The overall analysis of all the cases corresponding to
      the 1950-2000 period revealed that the prevalence of oral cancer in women has
      risen alarmingly and that the percentage of patients with advanced stages of
      tumor development continues to be high.

PMID- 16302459
TI  - Agnor as a marker of malignant transformation in odontogenic keratocysts.
AB  - Nucleolar Organizer Region (AgNOR) counts have been reported as a useful,
      complementary diagnostic tool for several neoplasias. The morphometric evaluation
      of AgNOR has also been shown to contribute to the detection of incipient cellular
      alterations. The aim of the present study was to perform a morphometric analysis
      of AgNOR in keratocysts (KC), and in three rare cases of malignant transformation
      of keratocysts (KCm) to explore their use as a marker of the process of malignant
      transformation in this entity. We performed a study of the 3 cases of keratocysts
      that had suffered transformation into squamous cell carcinoma (SCC) that were
      available in our files and of 8 cases of solitary keratocysts (KCs). Paraffin
      sections were silver stained and employed to perform a morphometric analysis of 7
      parameters related to number, size and shape of AgNORs. A comparative analysis of
      the epithelium of solitary keractocyts (KCs), the cystic epithelium adjacent to
      the area of transformation (KCm) and the epithelium of the SCC cords was
      performed. The epithelia of KCs and KCm exhibited statistically significant
      differences for four of the parameters analyzed: nuclear volume (VNUC), single
      AgNOR volume (VNOR), Total AgNOR per nucleus (TVNOR) and Contour Index of nuclei
      (CINUC). KCs and SCC exhibited statistically significant differences for all of
      the parameters. Given the ease with which this technique can be applied to
      routine histopathological material, we propose AgNOR evaluation as a diagnostic
      and prognostic aid in cystic entities that are suspected to have a neoplastic
      potential.

PMID- 16302460
TI  - A safe, effective and affordable HIV vaccine--an urgent global need.
AB  - The need for a safe, effective and affordable HIV vaccine has never been greater.
      In 2004 almost five million people became infected with HIV. In addition,
      providing access to antiretrovirals in Africa remains a huge challenge. A
      successful vaccine against HIV will probably need to stimulate the innate immune
      system, generate high levels of neutralizing antibodies, induce strong cellular
      immune responses and mucosal immunity, and should induce broad-spectrum immunity
      able to cover all HIV subtypes. In this review, we describe the limitations and
      challenges of developing a safe and effective HIV vaccine. We also emphasize
      possible approaches for overcoming immune escape in HIV infection, the lessons
      learned from the clinical trials of HIV-1 candidate vaccines, and the most
      important scientific highlights of the Keystone 2005 Symposium. When an effective
      vaccine is eventually found, we will face the enormous task of making it
      accessible to those who need it most.

PMID- 16302461
TI  - Enfuvirtide, the first fusion inhibitor to treat HIV infection.
AB  - Entry inhibitors are a new class of drugs for the treatment of HIV infection.
      Enfuvirtide is the first compound of this family to be approved for clinical use.
      It blocks HIV fusion to host cells. It is a synthetic peptide that mimics an HR2
      fragment of gp41, blocking the formation of a six-helix bundle structure which is
      critical in the fusion process. Enfuvirtide is a good therapeutic option as
      rescue therapy in combination with other active antiretrovirals and works against
      different HIV-1 variants, including all group M subtypes and group O. However, it
      is not active against HIV-2. The main mechanism of resistance to enfuvirtide
      depends of the selection of changes in a 10-amino acid domain between residues 36
      to 45 in the HR1 region of gp41. Single and double mutations in this region have
      been shown to result in high-level resistance to enfuvirtide. A negative impact
      of enfuvirtide-resistance mutations on viral fitness has been postulated, since
      resistance mutations tend to disappear soon after drug discontinuation and
      because immunologic benefits have been noticed despite virologic failure in
      patients undergoing enfuvirtide treatment.

PMID- 16302462
TI  - First-line antiretroviral therapy in Africa--how evidence-base are our
      recommendations?
AB  - According to the World Health Organization guidelines, a non-nucleoside reverse
      transcriptase inhibitor (NNRTI) along with two nucleoside reverse transcriptase
      inhibitors (NRTI) is the treatment of choice as first-line antiretroviral
      therapy. The results of the 2NN and different cohort studies performed in
      developed countries do not provide sufficient evidence by which to select between
      nevirapine and efavirenz as the first-line NNRTI for antiretroviral therapy in
      Africa. The current first-line NNRTI-containing antiretroviral therapy regimens
      used in Africa are certainly not ideal. Nevirapine interacts with rifampicin and
      therefore is not indicated in patients with tuberculosis. On the other hand,
      efavirenz should not be given to pregnant women. NNRTI-containing regimens may be
      less effective in women who received nevirapine monotherapy at delivery.
      Stavudine, used in the nucleoside backbone, may lead to lipoatrophy, lactic
      acidosis and polyneuritis. Zidovudine may cause serious anemia. Mainly because of
      cost considerations, the generic fixed-drug combination of nevirapine plus two
      NRTI seems at the moment to be the best choice. It is clear, however, that
      antiretroviral programs should not rely only on this combination for initial
      antiretroviral treatment. Most importantly, more HIV clinical trials need to be
      conducted in Africa, and African cohorts of patients on antiretroviral therapy
      need to be established in order to develop recommendations that are evidence
      based.

PMID- 16302463
TI  - High-risk dysmetabolism disorders associated with HAART-treated HIV disease, and
      reimbursement of lipid-lowering drugs, in a clinical and a socio-economic
      perspective.
AB  - The significant advances achieved in the management of HIV disease, thanks to
      highly active antiretroviral therapy, are at risk of being frustrated by the
      recent changes in the cost reimbursement rules for all lipid-lowering drugs
      available in Italy. Unfortunately, the remarkably increased life expectancy
      achieved since mid-1996 by HIV-infected persons after the introduction of
      protease inhibitors and combined anti-HIV treatment, is accompanied by
      significant risks of developing diet-uncontrolled hypercholesterolemia and/or
      hypertriglyceridemia, often concurrent with insulin resistance, visceral
      adiposity, and hypertension, all known factors which can strongly predispose to
      severe cardiovascular events. International and national health care system
      recommendations regarding the reimbursability of lipid-lowering drugs have to
      take into careful consideration of this "special" category of patients (HIV
      infected ones). These patients are exposed to a very frequent and severe, drug
      induced dyslipidemia, and a subsequently elevated and progressively increasing
      cardiovascular risk, despite their proportionally lower mean age compared with
      that of the general at-risk population, and the lack of many concurrent risk
      factors which are employed to calculate the strict need for a lipid-lowering
      therapy, and its consequent cost reimbursement by the different health care
      systems.

PMID- 16302464
TI  - Antiretroviral therapy in chronic liver disease: focus on HIV/HCV coinfection-
      statements of the First Italian Consensus Workshop.
AB  - Hepatitis C virus common transmission routes and HCV coinfection is frequent in
      persons living with HIV. Liver enzyme elevation following the initiation of
      antiretroviral therapy is frequently seen in HIV-infected patients with chronic
      liver disease, particularly those with chronic hepatitis C. This complication may
      lead to treatment discontinuation, complicating HIV therapeutic management.
      Multiple factors influence the risk of liver toxicity under antiretroviral
      therapy, including the specific drug in use (e.g. use of full doses of
      ritonavir), and environmental factors (e.g. alcohol abuse). However a beneficial
      effect of antiretroviral therapy on liver disease has been supported by some
      studies. Despite increasing knowledge of HCV/HIV coinfection, there is no clear
      consensus on how to treat HIV in HCV-coinfected patients An Italian group of
      experts were invited to discuss in detail the current risks and implications of
      antiretroviral treatment in HIV-infected persons with chronic hepatitis C, and
      their main conclusions are summarized in this consensus document.

PMID- 16302465
TI  - Proinflammatory cytokines in HIV disease-a review and rationale for new
      therapeutic approaches.
AB  - Antiretroviral drugs currently in use for treating HIV-1 infection are very
      effective at maintaining low viral loads and clinical stability, but have been
      limited by their inability to eradicate virus in infected individuals, resulting
      in the need for indefinite therapy. The inability of antiretroviral drug therapy
      to eliminate HIV-1 infection is thought to be due to incomplete restoration of
      host immunity to the virus. New strategies to improve control of HIV-1 infection
      during antiretroviral therapy should target enhancement of host immunity.
      Proinflammatory cytokines are the central mediators of both innate and adaptive
      immunity, and modulation of these cytokines has been shown to alter anti-HIV-1
      reactivity in vitro. Modulation of proinflammatory cytokines could therefore be
      utilized in strategies for immunotherapy of HIV-1 infection. The ultimate goal is
      to find regimens that could more durably suppress viral replication and
      potentially eliminate the need for indefinite antiretroviral therapy. This review
      presents what is known about the dysregulation of proinflammatory cytokines in
      HIV-1 infection, highlighting newly available immune-based therapies that could
      augment antiretroviral drug therapies.

PMID- 16302466
TI  - Criminality and mental health: implications for society.

PMID- 16302467
TI  - A quality of care issue: appropriate use and efficacy knowledge of five
      contraceptive methods: views of men and women living in low socioeconomic
      settlements of Karachi, Pakistan.
AB  - OBJECTIVE: To assess knowledge regarding availability, affordability, appropriate
      use and efficacy for five non-permanent contraceptive methods. METHODS: Married
      Muslim women and men (500 each) were randomly selected from two low socioeconomic
      settlements in Karachi, Pakistan. Interviews to assess their knowledge on a range
      of contraceptive and abortion themes were conducted. Four hundred men and 357
      women were selected from this larger sample based on their knowledge of condoms,
      withdrawal, oral pills, injectables and IUDs. RESULTS: Nearly half of the sampled
      men (56%) and women (48%) were contraceptive users. Knowledge regarding
      contraception, a specific method, its availability and affordability was high.
      Appropriate use knowledge for condoms was 73% among men (users 78%, non-users
      60%; p-value < or = 0.001 ) and 5% among women. Efficacy knowledge was generally
      poor. CONCLUSIONS: Low knowledge levels regarding appropriate use and efficacy
      even among contraceptive users suggests, that quality of family planning services
      should not be limited to service delivery issues but extend to appropriate use
      and efficacy knowledge levels among clients.

PMID- 16302468
TI  - Control of postpartum and post abortal haemorrhage with uterine packing.
AB  - OBJECTIVE: To determine safety and effectiveness of uterine packing to stop
      hemorrhage in postpartum and post abortal cases. METHODS: Patients who delivered
      either vaginally or via Caesarian section who developed primary post partum
      haemorrhage and post abortal patients developing primary post partum haemorrhage
      refractory to conventional medical treatment, were included in the study. Packing
      was done using 8-10 meters sterilized gauze from the fundus to cervix and was
      left for 12-24 hours or removed earlier in cases of failure to control
      hemorrhage. Morbidity and effectiveness was assessed. RESULTS: Intractable
      primary hemorrhage was encountered in 20 patients of whom 2 had bleeding after
      caesarian section, 14 after vaginal delivery and 4 patients had post abortal
      haemorrhage. Uterine atony was the commonest cause. Failure of packing to control
      haemorrhage was seen in 3 cases. It was successful in 17 cases. CONCLUSION:
      Whether used early or late in the management of post partum haemorrhage, uterine
      packing is a safe, quick and effective procedure.

PMID- 16302469
TI  - Comparison of 24 hours urinary citrate levels in urolithiasis patients and
      healthy controls.
AB  - OBJECTIVE: To identify the difference in urinary citrate excretion between Stone
      Formers (SF) and Healthy Volunteers (HV) as a metabolic risk factor, that
      predisposes to urinary stone formation and to compare levels of urinary citrate
      in (HV) with reference values. METHODS: The 24 hours urinary citrate was
      evaluated in 40 patients treated for renal citrate and declared stone free, and
      40 age matched healthy adults taken as controls. Both the groups had a similar
      living environment, extrinsic factors, diet and similar genetic descent. RESULTS:
      There was no significant difference in urinary citrate excretion level among
      stone formers (mean 262 SD 197) and normal volunteer subjects (mean 269 SD 140).
      Using the previously defined normal values (200) of urinary citrate in the local
      population, 55% of stone patients in our study group were hypocitric. While using
      the same value, 45% of our normal volunteers were also hypocitric. If 320 was
      taken as normal limit, 70% of the patient's population and 72% of controls were
      hypocitric. The prevalence of hypocitraturia was similar in the age matched adult
      groups. CONCLUSION: Certain intrinsic factors in our local subjects may account
      for the high prevalence of urolithiasis than in western population. Although the
      urinary citrate excretion of stone patients is similar to normal volunteers,
      uniformly low urinary citrate excretion may be a feature as a nation and not a
      predisposing factor for the lithogenesis. This supports the view that there may
      be more often prominent influences in stone formers possibly of genetic origin.

PMID- 16302470
TI  - Anaesthetic reasons for cancellation of elective surgical inpatients on the day
      of surgery in a teaching hospital.
AB  - OBJECTIVE: A prospect audit was conducted to find out the anaesthetic reasons for
      cancellation of surgical in patients on the day of surgery, and to plan for
      future suggestive corrective actions to reduce unnecessary cancellations.
      METHODS: The audit was conducted at Aga Khan University Hospital for one year
      from 1st January to 31st December 2003. Data was collected monthly on a pre
      designed form and the files of cases that were cancelled were reviewed by two
      consultants and labeled as justifiable or not justifiable cancellation. RESULTS:
      Eight thousand, five hundred and twenty six patients were scheduled for surgery
      during the study period, 359 (4%) were cancelled on the day of surgery after
      their names appeared on the operating room schedule. Only 28 (8%) of all
      cancellation were anaesthetic cancellations, 15 of which fell in nonjustifiable
      category. CONCLUSION: Although anaesthetic cancellations were only 0.3% of total
      elective admissions, this number can be improved further in the interest of the
      patients by implementing and following the recommendations that have been
      proposed following this audit.

PMID- 16302471
TI  - Role of isoniazid prophylaxis for prevention of tuberculosis in haemopoietic stem
      cell transplant recipients.
AB  - OBJECTIVE: To evaluate the role of isoniazid prophylaxis in prevention of
      tuberculosis among allogeneic stem cell transplant recipients. METHODS: This
      study was conducted at Armed Forces Bone Marrow Transplant Center Rawalpindi,
      Pakistan from July 2001 to October 2003. Patients suffering from various
      haematological disorders undergoing allogeneic stem cell transplantation were
      included in the study. The demographic information, primary diagnoses and
      relevant investigations were recorded. Patients had negative tuberculin skin
      tests and chest X-Ray at pre-transplant assessment. First 25 patients (group I)
      did not receive isoniazid prophylaxis while the next 25 (group II) were given
      isoniazid in a dose of 5-10 mg/kg (maximum 300 mg/day). Isoniazid prophylaxis was
      started on day-1 and continued for 6 months post transplant. The patients
      developing tuberculosis were treated with rifampicin, ethambutol, isoniazid, and
      pyrazinamide during first 3 months followed by 2 drugs for a total duration of 12
      months. Minimum follow up in group I and II was 783 and 403 days respectively.
      RESULTS: There was significant difference (p < 0.001) in frequency of
      tuberculosis between two groups. In group I, four patients developed Tuberculosis
      (frequency 16%) whereas none of the patients in group II had the disease. Out of
      these four cases 3 had extrapulmonary disease. One patient died two weeks after
      the start of anti tuberculosis treatment while others successfully completed the
      treatment. CONCLUSION: Tuberculosis in stem cell transplant recipients is an
      important opportunistic infection especially in areas of high disease prevalence
      like Pakistan. Isoniazid prophylaxis for 6 months is effective in preventing
      tuberculosis among this class of patients.

PMID- 16302473
TI  - Xanthogranulomatous pyelonephritis due to calculi: report of 63 cases and review
      of literature.
AB  - OBJECTIVE: To examine the relationship between clinical history and results of
      renal investigations in patients with xanthogranulomatous pyelonephritis.
      METHODS: A retrospective review was conducted on 63 cases presenting with
      histopathological diagnosis of xanthogranulomatous pyelonephritis between 1995 to
      2002, at the department of Urology, Bolan Medical College and Sandeman Provincial
      Teaching Hospital Quetta. RESULTS: There were 26 males and 37 females having an
      average follow up of two years. Positive findings on examination and
      investigations at presentation were fever and flank pain in 59 (93.6%) patients
      and pyuria in 34 (53.9%) patients. All the patients had renal and ureteric
      calculi with no or severe reduction in the function of the affected kidney on
      DTPA scan. Hypertrophy of the contra lateral kidney was seen in 56 (88.8%)
      patients. CONCLUSION: Xanthogranulomatous pyelonephritis is a common entity in
      this part of the world. Late referral leads to loss of the kidney. Pre-operative
      diagnosis of the condition is desirable and if surgery is mandatory then all
      infected tissues have to be removed.

PMID- 16302472
TI  - Prevalence of microalbuminuria in type 2 diabetic patients in Karachi: Pakistan:
      a multi-center study.
AB  - OBJECTIVE: To determine the frequency of microalbuminuria and its associations in
      type-2 diabetic subjects attending diabetes centers/clinics across Karachi,
      Pakistan. METHODS: Two thousand one hundred subjects with type-2 diabetes were
      screened for microalbuminuria using Micral test strip II. A single screening test
      was performed in 25 diabetes centers/units in different districts of Karachi from
      January 2003 to December 2003. RESULTS: The overall prevalence of
      microalbuminuria was 34%. Mean age of subjects was 53.1 years +/- 11.9 years,
      mean BMI was 25.8 +/- 4.1 and mean duration of diabetes was 8.8 +/- 5.21 years.
      Fifty seven percent were males and 43% females. Sixty two percent of the subjects
      had a systolic blood pressure > or = 130 mmHg. Forty five percent had a family
      history of diabetes and 5% had a family history of hypertension. Univariate
      analyses demonstrated significant associations between microalbuminuria and age,
      duration of diabetes, male gender, smoking status, microvascular and
      macrovascular complications, hypertension, high triglycerides, high serum LDL,
      low serum HDL, and high fasting and random blood sugars. When adjusted for the
      effects of other variables in the model, age, diastolic blood pressure, serum LDL
      and retinopathy were found to be significantly associated with microalbuminuria.
      CONCLUSION: The prevalence of microalbuminuria in type 2 diabetic subjects in
      this cross-sectional multicentre study across Karachi was 34% and this was
      significantly related to age, diastolic blood pressure, serum LDL and
      retinopathy.

PMID- 16302474
TI  - Risk factors assessment for hypertension in a squatter settlement of Karachi.
AB  - OBJECTIVE: To assess the risk factors for hypertension in adults (age more than
      15 years) in a squatter settlement of Karachi. METHODS: Cross-sectional survey of
      adults more than 15 years old in a squatter settlement of Karachi through random
      sampling method. RESULTS: A total of 327 adults were approached, 165 (50.5%) were
      males and 162 (49.5%) females. Blood pressure was measured in 63 (38%) males and
      135 (83%) females. Out of which, 11 (17.5%) males and 19 (14%) females were
      screened hypertensive. Hypertensives were older as compared to normotensives (p <
      0.001). The mean BMI of hypertensives (25.6 +/- 4.5 kg/m2) was significantly
      higher (p = 0.008) than normotensives (22.9 +/- 5.0 kg/m2). Hypertensives were
      9.7 times more likely to be diabetic as compared to normotensives in this study
      (p < 0.001). On analyzing the relationship of hypertension with other variables,
      no significant difference was noticed for education (p = 0.68), smoking status (p
      = 0.46), family history (p = 0.31) and occupation (p = 0.27). CONCLUSION:
      Prevention and control of hypertension is essential as the life expectancy is
      increasing in developing countries as well. The main emphasis according to this
      study, should be on controlling the BMI through weight reduction and regular
      exercise. Awareness about the risk factors for hypertension among the population
      is required to decrease the double burden on the society.

PMID- 16302475
TI  - Depression in primary care: difficulties and paradoxes.
AB  - The presentation of depression in primary care is in many ways different from
      that seen in psychiatric settings. The process of detection and treatment is also
      different. This is particularly so in developing countries like Pakistan, which
      has high prevalence rates of depression but poorly organized primary health care
      services and primary care physicians (PCPs) who have little psychiatric training,
      either at undergraduate or postgraduate levels. There is a need to review
      difficulties faced by primary care physicians in detection and management of
      depression. It is hoped this would lead to better and more effective management
      of depression at primary health care level.

PMID- 16302476
TI  - Cerebral deep venous thrombosis: case report and literature review.
AB  - The case of a 28 years old woman presenting with headache, drowsiness and
      vomiting of a short duration, is presented. She was diagnosed as deep cerebral
      venous thrombosis on the basis of MRI findings. Treatment with heparin gave
      completed recovery.

PMID- 16302477
TI  - Ischemic monomelic neuropathy: a complication of vascular access procedure.
AB  - Ischemic monomelic neuropathy (IMN) is an infrequently recognized type of
      ischemic neuropathy produced by shunting of blood or due to acute noncompressive
      occlusion of the major proximal limb artery. Most reports about this complication
      appear in the neurology literature. IMN predominantly occurs in diabetic patients
      with evidence of peripheral neuropathy and atherosclerotic peripheral vascular
      disease. We report a case of ischemic monomelic neuropathy occurring in a patient
      with end stage diabetic nephropathy following PTFE (polytetrafluoroethylene)
      graft placement in proximal upper limb for chronic maintenance hemodialysis.

PMID- 16302478
TI  - Lymphoepithelioma-like carcinoma of urinary bladder: (LELCA).
AB  - Lymphoepithelioma-like carcinoma of the bladder (LELCA) is an uncommon neoplasm
      of the urinary bladder and up till now only 49 cases have been reported in the
      English literature. It is imperative to distinguish between lymphoepithelioma
      like carcinoma and malignant lymphoma as primary bladder lymphoma is extremely
      rare. We report a case of a 55 year old lady who presented with the complaint of
      burning micturition and gross hematuria for the past 5 months. There were no
      other known comorbids. Pelvic ultrasound was normal. Cystoscopy showed a 4x4 cm
      sessile mass in the bladder. Histopathological examination was consistent with
      the diagnosis of lymphoepithelioma like carcinoma of the urinary bladder.

PMID- 16302479
TI  - General practice to family practice: a necessary change.

PMID- 16302481
TI  - Doctors, patients and informed consent.

PMID- 16302480
TI  - HIV testing in low prevalence populations.

PMID- 16302482
TI  - [Family physician has an important function in the early diagnosis. Do not wait
      until the kidney dies!].

PMID- 16302483
TI  - [Fatal delays until emergency call. Why do myocardial infarct patients give
      themselves so much time?. Interviewed by Judith Neumaier].

PMID- 16302484
TI  - [Patient with rhinoplasty. When does insurance pay?].

PMID- 16302485
TI  - [7-minute medicine instead of "consulting hour": the patient is dispatched].

PMID- 16302486
TI  - [Practical Nutritional therapy--a major component of the treatment and
      prophylaxis concept].

PMID- 16302487
TI  - [Homocysteine--risk factor or risk indicator?].
AB  - Since many patients experience cardiovascular events despite the absence of such
      classical risk factors as hypertension, high blood lipid levels, diabetes or
      smoking, the search for the underlying causes of arteriosclerotic vascular
      disease is continuing. The data accumulated to date are by no means unequivocal.
      Although the intake of vitamin B6, B12 and folic acid is associated with a
      decrease in the homocysteine level, more recent studies have failed to detect any
      significant reduction in the cardiovascular risk of these patients. Consequently,
      screening for homocysteine would not appear to make good sense at the present
      time.

PMID- 16302489
TI  - [Food allergies are often an unrecognized cause of clinical complaints].
AB  - While 6% of children under three years of age suffer from a food allergy, the
      figure for adults varies between 1.5 and 3%. Leading allergens in foodstuffs are
      glycoproteins having a molecular weight of between 10,000 and 60,000. The
      symptoms of an immediate type nutrient allergy mediated by IgE usually manifest
      within a matter of a few minutes to two hours after ingestion of the offending
      nutrient and take the form, for example, of tingling and itching, tissue swelling
      in the mouth, hoarseness, asthma, gastrointestinal complaints or acute urticaria;
      in severe cases anaphylactic shock may even occur. In contrast, no IgE antibodies
      are to be found in nutrient-induced enterocolitis, which is associated with
      diarrhea and vomiting occurring after a delay of one to six hours. Differential
      diagnostic considerations must include intolerance for certain foodstuffs, such
      as lactose intolerance, or pseudoallergic reactions.

PMID- 16302488
TI  - [Food-drug interactions: an underestimated risk].
AB  - With only few exceptions, administration of medicaments should, in principle, be
      independent of food intake (at least half an hour before or two hours after
      eating). This ensures uniform and assessable bioavailability. However, it also
      entails the risk that the patient is more likely to forget to take medication
      postponed to 2 hours after a meal, than when it is directly coupled to a meal.
      Certain foodstuffs or food constituents, such as, for example, grapefruit,
      Seville orange juice, red wine, alcoholic drinks in general, or large quantities
      of caffeine and garlic should be avoided during drug treatment. In addition,
      specific interactions with certain drugs must also be taken into account (e.g.
      MAO inhibitors and tyramine, curamine and vitamin K).

PMID- 16302490
TI  - [Diagnosing urinary incontinence in the elderly woman].
AB  - The diagnostic work-up of the elderly incontinent woman should always be done on
      an individual basis. Temporary episodes of incontinence caused by the use of
      certain drugs or by difficulty in getting to a toilet can be identified by a
      stepwise diagnostic approach and easily dealt with, for example, by replacing the
      drug by another, or effecting changes in the environment that improve the
      patient's access to a toilet. A mandatory aspect of the systematic diagnostic
      work-up is an attempt to achieve a positive effect through the use, for example,
      of anticholinergics or local hormone replacement therapy, so as to spare the
      patient stressful examinations.

PMID- 16302491
TI  - [Peculiar ways in medical students' education. Narrow-gauged physician as family
      physician substitute].

PMID- 16302492
TI  - [Certificate for the assistants. Unusual signature not allowed].

PMID- 16302494
TI  - [Federal Court sees offense against competition law. Low labor prices forbidden].

PMID- 16302493
TI  - [Gynecologists and ophthalmologists are advanced. Family physicians only a
      little].

PMID- 16302495
TI  - [Type 2 diabetics are high risk patients. Concerning LDL-cholesterol to approach
      effectively to two sources].

PMID- 16302496
TI  - [New approach in the therapy of type 2 diabetes mellitus. Exenatide lowers HbA1c
      and body weight].

PMID- 16302497
TI  - [Visit in the museum for sepulchral culture. Death between piety and technique].

PMID- 16302498
TI  - [Look diagnosis. Only a cosmetic problem?].

PMID- 16302499
TI  - It all started 25 years ago...

PMID- 16302500
TI  - Scar evaluation and management: recommendations.

PMID- 16302501
TI  - Gene delivery of PDGF for wound healing therapy.

PMID- 16302502
TI  - A novel approach for lower limb ulcers--Kerraboot.

PMID- 16302503
TI  - [New knowledge about amyloid can result in new treatment of Alzheimer disease].

PMID- 16302504
TI  - [Health of the elderly: an issue difficult to penetrate! The medical angle of
      approach does not give a sufficient answer, quality of life is equally
      important].

PMID- 16302505
TI  - [How do the elderly feel actually? Contradictory research results indicate both
      improved and impaired health].
AB  - As expected life span increases, researchers are asking if the years added to
      life are healthy or characterized by illness and disability. The question of
      compression or expansion of morbidity is complex and entails numerous
      methodological challenges. International and Swedish health trends in elderly
      populations are reviewed. Differences in methods concerning sampling, time period
      and health indicators make comparisons difficult and can explain why studies have
      divergent results. Despite the differences, a general trend can be seen showing
      an increase in poor health during the late nineties. However, the trend is seen
      primarily in disease and functional limitations, but not disability. If this is
      the case and this trend continues, the future may bring less disability than
      would be expected according to today's calculations based on demographic
      development. But at the same time, demands for medical care may increase due to
      increases in chronic illnesses that can be managed but not cured.

PMID- 16302506
TI  - [Acute poisonings among adults and adolescents in the year of 2000. Positive
      development--but alarming when it comes to narcotics and analgesics].

PMID- 16302507
TI  - [Over-the-counter paracetamol a common cause of poisoning among teenage girls.
      The Poison Control Center's report on analgesics poisoning].

PMID- 16302508
TI  - [Left ventricular reconstruction in ischemic heart disease. Good surgical
      alternative in advanced heart failure].
AB  - Left ventricular (LV) dilatation occurs after myocardial infarction and leads to
      heart failure. LV reconstruction or surgical ventricular restoration (SVR) by
      means of the Dor procedure reduces LV volume and restores normal LV shape. Mitral
      repair and surgery for ventricular tachycardia are performed as needed. SVR
      improves LV function and early and long-term results are good in terms of
      survival and arrhythmia control. International results as well as the experience
      of the procedure at Karolinska University Hospital are presented and illustrated
      with a case report.

PMID- 16302509
TI  - [What is the therapeutic effect if a patient gets better but nobody knows how
      much? Analysis of change when the data material consists of ordered categories].
AB  - Assessments on scales and questionnaires generate ordered categorical data.
      Characteristic feature is the ordered structure with lack of information
      regarding size and inter-categorical distances. These limited mathematical
      properties of ordered categorical data mean that the most common statistical
      methods for evaluation of change, the Student's paired t-test and the Wilcoxon
      sign rank test, are not appropriate to use as they are based on differences. This
      paper presents classical methods useful for dichotomous data but they are
      appropriate for dichotomised ordered categorical data as well.

PMID- 16302510
TI  - ["The institution is working"--a professor's group portraits of himself and his
      staff].

PMID- 16302511
TI  - [Need-directed leadership development for physicians. Concentration on the
      leadership can result in a better and more efficient work environment].

PMID- 16302512
TI  - [Asylum seeking children with refusal symptoms: politicizing delays medical
      anchorage and creates medical "care disputes"].

PMID- 16302513
TI  - [MTS, ATS, CTAS or ESI--dies anything fit the Swedish emergency department
      triage?].

PMID- 16302514
TI  - [External auscultation--a success in advanced and clinical education].

PMID- 16302515
TI  - [I wasn't drunk--it was vitamin B12 deficiency!].

PMID- 16302516
TI  - [Complementary and alternative medicine a question of patients' freedom of
      choice].

PMID- 16302517
TI  - [New concepts are questioned].

PMID- 16302518
TI  - [Project: personal nurses' budget].

PMID- 16302519
TI  - [Nursing specialties: breast care nurse].

PMID- 16302520
TI  - [Mobility--the project for maintaining personal independence and health in old
      age].

PMID- 16302521
TI  - [Professional handwashing for nurses].

PMID- 16302522
TI  - [A nursing concept for the future?].

PMID- 16302523
TI  - [Medicine discovers the differences between the sexes].

PMID- 16302525
TI  - [Baden-Wurttemberg].

PMID- 16302524
TI  - [Being bedridden is not one's fate].

PMID- 16302526
TI  - [Bayern].

PMID- 16302527
TI  - [Brandenburg, Mecklenburg-Vorpommern].

PMID- 16302528
TI  - [International form: the European Union and the nursing market].

PMID- 16302529
TI  - [Preserving inner balance in professional stress].

PMID- 16302530
TI  - [Lying in one's imagination].

PMID- 16302531
TI  - [Cherry stones--a vitamin depot].

PMID- 16302532
TI  - [Gratitude is necessary for nurses].

PMID- 16302533
TI  - [The daily race with time].

PMID- 16302534
TI  - Limitations to the spacing effect: demonstration of an inverted u-shaped
      relationship between interrepetition spacing and free recall.
AB  - The spacing effect refers to the finding that memory for repeated items improves
      when the interrepetition interval increases. To explain the spacing effect in
      free-recall tasks, a two-factor model has been put forward that combines
      mechanisms of contextual variability and study-phase retrieval (e.g.,
      Raaijmakers, 2003; Verkoeijen, Rikers, & Schmidt, 2004). An important, yet
      untested, implication of this model is that free recall of repetitions should
      follow an inverted u-shaped relationship with interrepetition spacing. To
      demonstrate the suggested relationship an experiment was conducted. Participants
      studied a word list, consisting of items repeated at different interrepetition
      intervals, either under incidental or under intentional learn instructions.
      Subsequently, participants received a free-recall test. The results revealed an
      inverted u-shaped relationship between free recall and interrepetition spacing in
      both the incidental-learning condition and the intentional-learning condition.
      Moreover, for intentionally learned repetitions, the maximum free-recall
      performance was located at a longer interrepetition interval than for
      incidentally learned repetitions. These findings are interpreted in terms of the
      two-factor model of spacing effects in free-recall tasks.

PMID- 16302535
TI  - Blocking is sensitive to causal structure in 4-year-old and 8-year-old children.
AB  - In a contingency learning task, 4-year-old and 8-year-old children had to predict
      the outcome displayed on the back of a card on the basis of cues presented on the
      front. The task was embedded in either a causal or a merely predictive scenario.
      Within this task, either a forward blocking or a backward blocking procedure was
      implemented. Blocking occurred in the causal but not in the predictive scenario.
      Moreover, blocking was affected by the scenario to the same extent in both age
      groups. The pattern of results was similar for forward and backward blocking.
      These results suggest that even young children are sensitive to the causal
      structure of a contingency learning task and that the occurrence of blocking in
      such a task defies an explanation in terms of associative learning theory.

PMID- 16302536
TI  - Relative weight of local and global properties depends on both the position of
      local elements and the saliency of global form.
AB  - Love, Rouder, and Wisniewski (1999) and Ripoll and Marty (2005) showed that
      subjects could process global properties very quickly in a same/different task on
      abstract visual scenes for which the conspicuity of local and global properties
      had been controlled. In this new experiment, two important new factors were
      manipulated: saliency of the global pattern and location of local similarity. The
      results showed that the saliency of the global form as well as the location of
      local similarity determines the strength of global and local effects. Global
      effects continue to manifest themselves even when the extraction of the global
      form is difficult. Finally, the whole pattern of results suggests that local and
      global processing proceeds simultaneously and involves two attentional systems
      whose spatial characteristics are very different.

PMID- 16302537
TI  - A pictorial version of the Extrinsic Affective Simon Task: sensitivity to
      generally affective and phobia-relevant stimuli in high and low spider fearful
      individuals.
AB  - This study assessed whether a pictorial, rather than a verbal, Extrinsic
      Affective Simon Task (EAST: De Houwer, 2003) is, 1) sensitive to the affective
      valence of normatively positive, neutral, and negative pictures, 2) sensitive to
      interindividual differences pertaining to fear-relevant affective associations,
      and 3) a valid predictor for strategic and/or reflexive fear responses. High (n =
      35) and low (n = 35) spider fearful individuals completed an EAST comprising of
      universal positive, negative, neutral, and spider pictures. The pictorial EAST
      was sensitive to normatively valenced stimuli, tended to differentiate between
      high and low fearful individuals with respect to spider pictures, and showed
      independent predictive validity for avoidance behavior.

PMID- 16302538
TI  - Automatic processing of dominance and submissiveness.
AB  - We investigated whether people are able to detect in a relatively automatic
      manner the dominant or submissive status of persons engaged in social
      interactions. We used a nonaffective variant of the affective Simon paradigm of
      De Houwer and Eelen (1998) in which participants responded by saying either
      "dominant" or "submissive" depending on the right or left spatial position of a
      target person who was engaged as either the dominant or the submissive agent in a
      social interaction. We observed that responses were facilitated when the status
      connotation of the target person and the correct response corresponded. These
      results provide new information about the automatic nature of information related
      to emotion-antecedent appraisals.

PMID- 16302539
TI  - Valence, comparison focus and self-positivity biases: does it matter whether
      people judge positive or negative traits?
AB  - The present research questions whether mere valence affects self-other
      comparisons in the domain of trait characteristics. While some previous studies
      have reported greater positivity bias for the self when traits were positive than
      when traits were negative, we suggest that this is an ambiguous finding, because
      valence and content were confounded. When we unconfounded content and valence,
      valence had no effect on the magnitude of self-positivity bias displayed. We also
      replicate several findings for our unconfounded set of traits. Firstly, comparing
      others to the self, rather than comparing the self to others, lowered self
      positivity for positive and negative traits (focus effect). Secondly, extremely
      positive and negative traits triggered greater positivity bias than did more
      moderately evaluated ones. Finally, we suggest that comparative self-positivity
      biases may be based on a general positivity bias.

PMID- 16302540
TI  - When should ethics consultants risk giving their personal views?

PMID- 16302541
TI  - Specters, traces, and regret in ethics consultation.

PMID- 16302542
TI  - "Amputate my arm please--I don't want it anymore".

PMID- 16302543
TI  - Helping staff help a "hateful" patient: the case of T.J.

PMID- 16302544
TI  - Misjudging needs: a messy spiral of complexity.

PMID- 16302545
TI  - The sound of chains: a tragedy.

PMID- 16302546
TI  - "But how can we choose?".

PMID- 16302547
TI  - Ethics first aid: reframing the role of "principlism" in clinical ethics
      education and practice.

PMID- 16302548
TI  - Confidence and knowledge of medical ethics among interns entering residency in
      different specialties.

PMID- 16302549
TI  - In defense of tongue splitting.

PMID- 16302550
TI  - Cochlear implants in children: ethics, informed consent, and parental decision
      making.

PMID- 16302551
TI  - Dying while homeless: is it a concern when life itself is such a struggle?

PMID- 16302552
TI  - Raging against the night: dying homeless and alone.

PMID- 16302553
TI  - Ethical dilemmas encountered by clinical researchers.

PMID- 16302554
TI  - Evidence based or theoretical concern? Pseudotumor cerebri and depression as
      acitretin side effects.
AB  - Oral retinoids are among the first line agents for treatment of pustular and
      erythrodermic psoriasis, and they are effective in combination with phototherapy
      and other topical and systemic agents for the treatment of plaque psoriasis.
      Acitretin is the leading oral retinoid used today for the treatment of psoriasis.
      Recently, possible side effects such as pseudotumor cerebri and depression have
      gained a warning and precaution respectively on the acitretin package insert.
      This paper presents a review of the scientific literature and attempts to clarify
      whether warnings of these side effects have arisen from a scientific evidence
      base or from theoretical concern/class labeling. A paucity of scientific evidence
      was found in this review for acitretin-associated pseudotumor cerebri and
      depression. The authors conclude that these 2 acitretin side effects must be
      further investigated to assess whether these associations are scientifically
      certain or if class labeling has led to inclusion in the package insert.

PMID- 16302555
TI  - Factors affecting prescription of ultra-high potency topical corticosteroids in
      skin disease: an analysis of US national practice data.
AB  - Of the topical preparations available, the ultra-high potency corticosteroids
      have an important role in treating psoriasis. However, the use of these agents in
      many other conditions and patient populations may not be appropriate. This study
      examines the prescribing patterns of Class I topical corticosteroids in patients
      with skin disease by analyzing data from the National Ambulatory Medical Care
      Survey (1990-2000). Of the nearly 718 million visits for skin disease, Class I
      topical corticosteroids were prescribed in nearly 3% of all skin disease-related
      visits, with prescription rates being highest in psoriasis (22%). The study found
      greater prescription rates of Class I topical steroids by dermatologists compared
      to non-dermatologists [Odds Ratio (OR) = 4.39 (95% CI: 2.15, 8.99)]. However,
      there were also a large number of questionable prescriptions for other
      conditions, which could be construed as misuse of these medications. Despite
      limitations and the potential dubious use seen here, Class I topical
      corticosteroid use is relatively commonplace. Education efforts and novel
      preparations of Class I agents will help to ensure the best possible care for
      patients suffering from significant skin diseases like psoriasis.

PMID- 16302556
TI  - Imiquimod as an antiangiogenic agent.
AB  - Imiquimod (imidazoquinoline 5%) is a topical immune response modifier agent that
      inhibits angiogenesis, the growth of new blood vessels. In addition to its
      stimulation of cell-mediated immunity, imiquimod's antiangiogenic activity
      contributes to its clinical efficacy by interfering with pathological
      neovascularization that promotes disease progression. The antiangiogenic
      mechanisms of imiquimod are due to its: 1) induction of cytokines that themselves
      inhibit angiogenesis (interferons, IL-10, IL-12); 2) local up-regulation of
      endogenous angiogenesis inhibitors (TIMP, TSP-1); 3) local down-regulation of pro
      angiogenic factors (bFGF, MMP-9); and 4) promotion of endothelial cell apoptosis.
      This report discusses these mechanisms and the rationale for imiquimod's use as
      an antiangiogenic agent. Key principles of antiangiogenic therapy are presented
      to describe how imiquimod may be applied in a well-tolerated fashion to treat a
      broad range of angiogenesis-dependent dermatological conditions, including
      actinic keratosis (AK), basal cell carcinoma (BCC), squamous cell carcinoma
      (SCC), lentigo maligna, hemangiomas, Kaposi's sarcoma, pyogenic granuloma, and
      external genital warts.

PMID- 16302557
TI  - Safety and efficacy of alefacept in elderly patients and other special
      populations.
AB  - BACKGROUND: The safety of biologic agents for psoriasis treatment is of
      particular importance in patient groups at higher risk for adverse events. We
      assessed the safety and efficacy of alefacept in elderly, obese, and diabetic
      patients with moderate to severe chronic plaque psoriasis by integrating data
      from phase 2 and 3 clinical studies and their extensions. OBSERVATIONS: Ninety
      nine elderly, 652 obese, and 122 diabetic patients received at least 1 course of
      alefacept. In each cohort, accidental injury, headache, and pharyngitis were
      among the most common adverse events; infections were primarily common colds; and
      malignancies were mostly skin carcinomas. No opportunistic infections were
      reported. Safety was maintained over repeated courses. The safety profile of
      alefacept in each cohort was consistent with that of the overall population;
      however, additional data are needed to confirm our findings in the elderly and
      diabetic subgroups in the later courses due to the limited sample sizes. In
      course 1, 24% to 33% of patients achieved 75% or greater improvement in Psoriasis
      Area and Severity Index (PASI) at any time, with further enhancement of benefit
      with subsequent courses (eg, course 3, 41% to 58%). CONCLUSIONS: Alefacept was
      well-tolerated and effective in elderly, obese, and diabetic patients with
      psoriasis.

PMID- 16302558
TI  - Cumulative irritation potential of metronidazole gel compared to azelaic acid gel
      after repeated applications to healthy skin.
AB  - BACKGROUND: Metronidazole 0.75% gel and azelaic acid 15% gel are commonly used to
      treat rosacea. Irritation is a common side effect. OBJECTIVE: To assess the
      cumulative irritation potential of metronidazole 0.75% gel and azelaic acid 15%
      gel. METHODS: Metronidazole 0.75% gel, azelaic acid 15% gel, and a white
      petrolatum negative control were applied under occlusive conditions to the upper
      back of a total of 33 healthy subjects. There were twelve 24-hour applications (4
      times a week) and three 72-hour applications on weekends during a 3-week period.
      Skin reactions (erythema score +/- other local reaction) were assessed within 15
      to 30 minutes of removal of the products. RESULTS: The mean cumulative irritancy
      index of metronidazole 0.75% gel was significantly lower than that of azelaic
      acid 15% gel and not significantly higher than the negative control product.
      There was increasing cumulative irritancy with azelaic acid; no cumulative
      irritancy was seen for either metronidazole or white petrolatum. CONCLUSION:
      Metronidazole 0.75% gel is less irritating in sustained use than azelaic acid 15%
      gel.

PMID- 16302559
TI  - Puerto Rico psoriasis study group: efficacy and safety of etanercept.
AB  - BACKGROUND: Although major advances in the understanding of its pathogenesis have
      been achieved, psoriasis remains an incurable disease. In April 2004, etanercept,
      an antagonist of TNF-alpha, was approved by the Food and Drug Administration for
      the treatment of chronic, moderate to severe plaque psoriasis in adults. In this
      study we intend to document the efficacy and further establish the safety profile
      of etanercept for the treatment of moderate to severe psoriasis in our population
      and compare our data to the Leonardi et al study published in 2003. METHODS: A
      total of 26 patients were followed for a period of 24 weeks. Subjects were
      administered 25 mg of etanercept subcutaneously twice weekly for 24 weeks.
      Patients were seen every 4 weeks to measure clinical improvement by means of the
      psoriasis area and severity index (PASI) scores. Development of side effects was
      also assessed. RESULTS: Ninety-two percent of the patients had an improvement of
      greater than 50% in their PASI score, with 79% of these patients with a PASI
      improvement of 75% or greater. Adverse events were uncommon and none required the
      permanent discontinuation of treatment. CONCLUSION: Treatment with etanercept was
      well-tolerated and resulted in significant sustained improvement of psoriasis
      throughout a period of 24 weeks. Our data strongly correlates with the findings
      reported by Leonardi et al in 2003.

PMID- 16302560
TI  - Cystic acne improved by photodynamic therapy with short-contact 5-aminolevulinic
      acid and sequential combination of intense pulsed light and blue light
      activation.
AB  - Photodynamic therapy with short-contact 5-aminolevulinic acid (Levulan Kerastick,
      Dusa Pharmaceuticals, Inc.) and activation by intense pulsed light in an initial
      treatment and blue light in 3 subsequent treatments has resulted in significant
      improvement in severity of acne, reduction in the number of lesions, improvement
      in skin texture, and smoothing of scar edges in an Asian patient with severe
      (class 4) facial cystic acne and scarring.

PMID- 16302561
TI  - Bullous pemphigoid following therapy with an oral beta-blocker.
AB  - A causal relationship is thought to exist between several medications and the
      development of bullous pemphigoid. Commonly implicated medications include
      furosemide, penicillins, and ibuprofen. The following is a case report of an
      elderly man who developed generalized bullous pemphigoid for the first time after
      beginning therapy with an oral beta-blocker. A literature search revealed only 2
      other reports of beta-blocker associated bullous pemphigoid. As both bullous
      pemphigoid and beta-blockers are common in elderly patients, dermatologists may
      want to consider beta-blockers as potential etiological agents in the development
      of bullous pemphigoid.

PMID- 16302562
TI  - Dermatofibrosarcoma protuberans following tanning bed use.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a rare, slowly growing, malignant
      dermal tumor first described by Darier and Ferrand in 1924. It typically occurs
      in individuals aged 20 to 40 years and frequently arises on the trunk. Although
      the cellular origin of DFSP is not entirely clear, dermal stem cells or
      undifferentiated mesenchymal cells with fibroblastic, muscular, and
      neuroectodermal features have been implicated. DFSP is a locally aggressive tumor
      with a high recurrence rate, largely attributed to the spread of tumor by direct
      local invasion through peripheral and deeply penetrating neoplastic cells into
      subcutaneous tissue and muscle. As such, there is growing evidence that Mohs
      micrographic surgery is the treatment of choice. Although reports of chromosomal
      aberrations and gene mutations have been described in the literature, excessive
      sun exposure is not regarded as a risk factor for the development or progression
      of DFSP. We describe a case of DFSP in a patient with a history of prolonged
      tanning bed use.

PMID- 16302563
TI  - Tolerance to calcitriol and tacalcitol in three patients with allergic contact
      dermatitis to calcipotriol.
AB  - We describe 3 cases of psoriatic patients who developed a severe eczematous
      eruption after the use of calcipotriol ointment. For all of them, the dermatitis
      recovered after the suspension of the calcipotriol ointment and topical
      application of corticosteroids. We performed patch tests with the standard series
      of SIDAPA (Italian Society of Environmental, Occupational and Allergological
      Dermatology), with an integrative series of vehicles and preservatives, with the
      commercial ointment containing calcipotriol, with its excipients and, finally,
      with a series of diluted calcipotriol in isopropanol and petrolatum. They all
      revealed a strong allergic reaction to calcipotriol and also to its dilution in
      isopropanol (for all patients) and in petrolatum (only one patient). It is
      interesting to underline that the reactions always occurred on the legs, even if
      the patients had applied the ointment elsewhere. We can hypothesize that the
      venom stasis dermatitis of the legs, associated with xerosis, may have favored
      the penetration of the drug through the skin, increasing the risk of allergic
      contact sensitization. Finally, cross-reactivity to other vitamin D3 analogue,
      tacalcitol, and calcitriol was excluded.

PMID- 16302564
TI  - Treatment of erythematotelangiectactic rosacea with a KTP YAG laser.
AB  - The flushing and telangiectasias associated with rosacea are notoriously
      difficult to treat with standard medications. Newer technologies, namely medical
      lasers and light sources, have made it possible to control and improve
      erythematotelangietatic signs of rosacea. The potassium-titanyl-phosphate laser
      in particular is an efficacious and safe tool for treatment of this disease.

PMID- 16302565
TI  - Trichophyton tonsurans associated tinea corporis infection with the development
      of Majocchi's granuloma in a renal transplant patient.
AB  - Trichophyton tonsurans is an uncommon cause of tinea corporis, and an even more
      uncommon cause of Majocchi's granuloma. We report a patient who developed tinea
      corporis with Majocchi's granuloma from T. tonsurans infection. Immunocompromised
      hosts are predisposed to develop cutaneous fungal infections, as was the case
      with this patient. Majocchi's granuloma is a rare complication with
      immunosuppression, but is significant to consider when a fungal infection is
      suspected because it may require more aggressive therapy.

PMID- 16302566
TI  - Q-switched alexandrite laser-assisted treatment of melasma: 2-year follow-up
      monitoring.
AB  - Melasma is a common disorder of hyperpigmentation involving sun exposed face and
      neck areas. Three clinical patterns of melasma are recognized: the centrofacial,
      the malar, and the mandibular ones. Several factors have been implicated in the
      pathogenesis of this disorder including pregnancy, oral contraceptive therapy,
      sun exposure, genetic factors, cosmetics, and race. This condition is most
      frequently observed in women and affects all racial groups; however, it is
      commonly found in darker-complexioned individuals (skin types IV through VI) and
      in Asian women who live and work under strong sunlight exposure for long periods.
      Melasma is very difficult to treat and often resistant to therapy. Treatment of
      melasma includes various hypopigmenting agents, chemical peeling, and laser
      surgery with unsatisfactory results. We report 3 cases of facial melasma
      successfully treated with a Q-switched Alexandrite laser.

PMID- 16302567
TI  - Nodular melanoma: how current approaches to early detection are failing.

PMID- 16302568
TI  - Exploring the issue of abused hyperactive children in Taiwan.

PMID- 16302569
TI  - Infantile wheezing and bronchodilator treatment.
AB  - Wheezing is a symptom, not a diagnosis. Wheezing disorders are not equal to
      childhood asthma. Wheezing in the youngest children is often episodic, associated
      with upper respiratory infection. Early wheezing disorders, particularly in the
      first 2-3 years of life, should be considered as largely independent of later
      childhood asthma. It is difficult to distinguish an initial episode of asthma
      triggered by a viral respiratory infection from acute viral bronchiolitis. Most
      of the infants with wheezing have transient conditions associated with diminished
      airway function at birth and do not have increased risks of asthma or allergies
      later in life. There is no evidence for an overall beneficial clinical effect of
      nebulized a2-agonists in acute severe wheezing episodes or acute bronchiolitis in
      infants, although some may seem to respond.

PMID- 16302570
TI  - Persistent truncus arteriosus: twenty years experience in a tertiary care center
      in Taiwan.
AB  - BACKGROUND: Persistent truncus arteriosus (PTA) is a rare congenital heart
      disease. The disease spectrum and outcome in the Oriental are still unclear.
      METHODS AND RESULTS: A total of 35 patients with PTA were identified from the
      Pediatric Cardiology Database of this institution, giving an incidence of 0.47%.
      According to the Van Praagh classification, we found type A1 in 16, A2 in 10, A3
      in 4 and A4 in 5 patients. The most common truncal valves were still tricuspid
      (57.1%) and quadricuspid (28.5%), with the latter being associated with moderate
      to severe truncal regurgutation. Eleven patients had not received surgery and all
      died. We classified the era of operation as early (between 1980 and 1995) or late
      (1996-2001), and further classified the type of PTA as simple (type A1 or A2) or
      complex (interrupted aortic arch-A4, absent orifice of one PA from truncal root
      A3 or moderate truncal valve insufficiency). The overall surgical mortality was
      67%. Statistical analysis revealed that age at operation (older than 6 months),
      early operation era and complex PTA were risk factors for survival. CONCLUSIONS:
      PTA is a rare form of congenital heart disease in Taiwan and probably also in the
      Oriental. The surgical reparation seems to improve with experience. Early
      operation may prevent pulmonary vasculopathy. However, the results in complex PTA
      remain poor.

PMID- 16302571
TI  - Positive blood cultures in pediatric emergency department patients:
      epidemiological and clinical characteristics.
AB  - OBJECTIVE: To determine the frequency of the emergency department (ED) visits of
      bacteraemic children and to compare the clinical characteristics of the
      discharged patients with those of the admitted patients. METHODS: We
      retrospectively reviewed the visits of the pediatric ED patients younger than 18
      years old in a medical center located in southern Taiwan during a 17-month period
      between September 1, 2001 and January 31, 2003, and the blood cultures
      significant organisms were isolated. RESULTS: Totally, 48,279 pediatric patients
      visited the ED. The blood cultures were ordered for 16% (7,923) of the patients,
      whose positive result was 4.2% (329), whose 0.8% (60) was, however, from where
      true pathogen isolated, and whose contamination rate was 3.4% (269). Seventeen
      patients (28%) were discharged and 43 patients (72%) were admitted who
      subsequently proved to be bacteraemic. The latter had significantly higher white
      blood cell count (13.03+/-5.75 vs. 8.75+/-3.25 x10(3)/mm(3)), higher C-reactive
      Protein (75.48+/-59.48 vs. 12.96+/-0.73 mg/L), more antibiotic treatment and more
      Pneumococcus bacteremia (28% vs. 0%) than the former which had significantly more
      Moraxella catarrhalis bacteremia (29.4% vs. 0%) than the latter. Non-typhi
      Salmonella were the most common isolated organisms, regardless of the ED children
      who were discharged (52.9%) or admitted (37.2%). There were no significant
      differences between the two groups in terms of the distribution of gender, age,
      major initial diagnosis and the percentage of band and segment form of WBC. Of
      the seventeen pediatric patients who were discharged initially, no focal
      suppurative complication or mortality was disclosed later. CONCLUSION: Careful
      clinical examination and laboratory data assessment (WBC and CRP) in the ED
      prevented no discharge of some pediatric patients who were subsequently found to
      be bacteremic. As the pathogens of the ED patients who were discharged earlier
      were rarely susceptible to the selected antibiotics, we believe that close
      contact and regular follow up of these patients who have the blood cultures done
      in the ED are preferable to empiric antibiotic therapy.

PMID- 16302572
TI  - Transcatheter closure of secundum atrial septal defect using the Amplatzer Septal
      Occluder: initial results of a single medical center in Taiwan.
AB  - The Amplatzer Septal Occluder (ASO) is the first and only device to receive full
      approval for clinical use in patients with secundum atrial septal defect (ASD)
      from the United States Food and Drug Administration. This study reports the
      device's initial results in Taichung Veterans General Hospital, a tertiary
      medical center in central Taiwan. Between October 2001 and December 2004, 39
      consecutive patients (31 females, 8 males) with secundum ASD underwent attempt at
      transcatheter closure using the ASO under general anesthesia and transesophageal
      echocardiographic guidance. Six patients were excluded due to deficient rims (2
      patients), multiple ASDs (1 patient), too large a defect (1 patient), too small a
      defect (1 patient) and 1 patient with associated atrial flutter. A total of 33
      patients (26 females, 7 males) underwent the device closure procedure. The median
      age was 10.6 years (range 3.1-57.5 years) and median weight was 42 kg (range 13.5
      73 kg). The median Qp/Qs ratio was 2.12 (range 1.02-5.52). The median balloon
      stretched diameter of the defect by sizing plate was 16 mm (range 5-37 mm). A
      total of 33 devices (median size 17 mm, range 7-38 mm) were implanted in 33
      patients. The median fluoroscopy time was 10.1 minutes (range 5.9-29 minutes) and
      the median procedure time was 55 minutes (range 30-105 minutes). Complications
      included asymptomatic device embolization to the right ventricle in 1 patient
      (surgical removal) and transient complete atrioventricular block in 1 patient.
      Follow-up echocardiography at 10 minutes, 24 hours, 1 month, 6 months, 1 year and
      2 years after the procedure showed complete closure rates of 76% (25/33), 91%
      (30/33), 100% (32/32), 100% (22/22), 100% (22/22), and 100% (9/9), respectively.
      In conclusion, transcatheter closure of secundum ASD using the Amplatzer Septal
      Occluder is safe and effective, with a very low complication rate.

PMID- 16302574
TI  - Diffuse type pulmonary arteriovenous malformations: report of one case.
AB  - Pulmonary arteriovenous malformations are direct communications between pulmonary
      arteries and veins via a tortuous vascular space. They can cause severe pulmonary
      and neurologic complications. Most PAVMs are located in the lower lobes and can
      be seen on radiography or angiography. However, a few patients with PAVMs have a
      more severe and diffuse pattern of disease. These patients generally present with
      more profound cyanosis and a poorer prognosis. The widespread distribution and
      small size of these lesions make both diagnosis and management very difficult. We
      report a 12-year-old patient with diffuse bilateral PAVMs confirmed by contrast
      echocardiography and technetium-labeled macroaggregated albumin perfusion scan.

PMID- 16302573
TI  - Tissue necrosis after intramuscular administration of diclofenac: report of one
      case.
AB  - A seven-year-old girl received intramuscular injection of diclofenac for
      symptomatic treatment of her fever. Aseptic tissue necrosis occurred around the
      injection site. Although there was no sequela left after wound care and surgical
      interventions, unwanted morbidity had resulted. Fever is just a symptom but not a
      disease itself. We should work more aggressively to evaluate the potential
      infection rather than treat the fever only. If it is necessary to lower the body
      temperature, external cooling, oral medication would suffice. Suppository is
      reserved for children when oral intake is not possible, and injection should be
      the last resort.

PMID- 16302575
TI  - Moyamoya syndrome with inherited proteins C and S deficiency: report of one case.
AB  - Moyamoya disease (MMD) is a vascular abnormality characterized by progressive
      narrowing of the internal carotid, middle, anterior and posterior cerebral
      arteries and the development of basal collaterals forming the classic
      angiographic appearance-moyamoya. Protein C (PC) and its cofactor, protein S
      (PS), which are vitamin-K dependent, act as inhibitors of coagulation cascade by
      inactivating factor Va and factor VIIIa and facilitating thrombolysis.
      Deficiencies of these proteins leading to a prothrombotic state increase the risk
      of ischemic cerebrovascular accident. Herein we report a 3-year-old girl, who had
      an acute onset of right-side hemiparesis during an episode of herpetic
      gingivostomatitis. She was noted to have moyamoya syndrome in the angiographic
      examination and was later proved to have inherited deficiencies of both PC and
      PS. She received warfarin medical treatment and then bilateral encephalo-duro
      arterio-synangiosis (EDAS) and encephalo-myo-synangiosis (EMS) due to
      neurological deterioration and is now under the use of low molecular weight
      heparin for preventing further ischemic stroke. The motor deterioration improved
      after medical and surgical intervention. We conclude that coagulopathy like PC or
      PS deficiency should be considered in children presenting with moyamoya syndrome.

PMID- 16302576
TI  - 49, XXXXY syndrome with severe vesico-ureteral reflux and hydronephrosis: report
      of one case.
AB  - The 49, XXXXY syndrome was first reported in 1960. It represents a rare sex
      chromosome aneuploidy syndrome. Some consider it as the most severe variant of
      Klinefelter syndrome (47, XXY). The approximate incidence is 1 in 85,000 male
      births. The karyotype arises from maternal non-disjunction during both meiosis I
      and meiosis II. The clinical presentations of 49, XXXXY syndrome include mental
      deficiency, hypogonadism, severe speech delay, multiple skeletal anomalies,
      cardiac defects and characteristic facial features. It might be mistaken for Down
      syndrome and needs chromosome analysis for confirmation. According to literature
      review, urinary tract anomaly in association with 49, XXXXY syndrome was
      extremely rare. Here we report a case of 49, XXXXY with Down syndrome-like facial
      dysmorphism, who was found to have patent ductus arteriosus and hypotonia.
      Moreover, he also got grade V vesico-ureteral reflux, R't with hydronephrosis and
      urinary tract infection. We hope to remind clinicians to arrange chromosomal
      analysis if multiple congenital anomalies exist in a neonate. And remember to
      exclude congenital genitourinary tract anomaly if karyotype 49, XXXXY is
      diagnosed.

PMID- 16302577
TI  - Child abuse: acute water intoxication in a hyperactive child.
AB  - A 4-year-8-month-old boy was brought to our emergency department with coma and
      seizure. Initial physical examination showed evidence of physical child abuse and
      sudden body weight gain of 3.4 kg in one day. The laboratory results showed
      normal renal function with severe hyponatremia and the MRI study showed diffuse
      brain swelling. All of these findings were compatible with the diagnosis of acute
      water intoxication. Careful history taking from the boy and his parents
      separately confirmed the course of chronic polydipsia with acute compulsive water
      drinking. After clinical assessment and follow-up by psychiatrist, the patient
      was diagnosed with hyperactivity disorder. We present this case and show the
      possibility of correlation between compulsive water drinking, child abuse and
      hyperactivity disorder on acute water intoxication.

PMID- 16302578
TI  - Central diabetes insipidus following intracranial hemorrhage due to vitamin K
      deficiency in a neonate.
AB  - A previously healthy 30-day-old girl presented with seizures, irritability and
      inability to sleep for three days. Vitamin K was not given just after birth. She
      was lethargic. A multifocal clonic seizure was evident during examination.
      Anisocoria was diagnosed on eye examination. Brain magnetic resonance imaging
      showed intracerebral hemorrhage, ventricular dilatation, and hematoma in the left
      temporofrontal region extending to the hypothalamus. Central diabetes insipidus
      was diagnosed by water deprivation due to dehydration and hypernatremia, and then
      desmopressin was added to phenobarbital. The possible mechanism of central
      diabetes insipidus in our patient is damage of vasopressin pathway resulting from
      compression of hemorrhage. An operation of ventriculoperitoneal shunt was also
      performed due to hydrocephalus. While she was symptom-free except for
      neurological sequel during routine control examinations after discharging from
      hospital, the parents said that she died, most probably from bronchopneumonia, at
      the age of 7.5 months. In conclusion, we emphasize that prophylactic vitamin K
      should be administrated to all babies just after birth, and infants with
      intracranial hemorrhage should carefully be monitored for central diabetes
      insipidus.

PMID- 16302579
TI  - Hyperammonemia in neonates: a transient phenomenon or an early sign of inborn
      errors of metabolism?

PMID- 16302580
TI  - Insulin resistance in obese adolescents.
AB  - The prevalence of obesity in adolescents is increasing rapidly. Obesity is
      associated with insulin resistance, which increases the risk for type 2 diabetes.
      We investigated insulin resistance in obese adolescents and its relationship to
      acanthosis nigricans. Height, weight and body mass index (BMI) were measured and
      each was expressed as a standard deviation score (SDS) based on national growth
      standards. Insulin resistance was estimated by using the homeostasis model
      assessment (HOMA-IR) score, calculated as fasting insulin (microU/mL) x fasting
      glucose (mmol/L)/22.5. Obese adolescents had significantly greater weight-SDS,
      BMI-SDS, fasting insulin levels, and HOMA-IR than did controls with normal
      weight. Acanthosis nigricans was present in 58.4% of obese adolescents. Fasting
      insulin levels and BMI-SDS were positively correlated with the degree of
      acanthosis nigricans (r = 0.383, P<0.0001 and r = 0.164, P < 0.05, respectively).
      On multiple regression analysis, HOMA-IR and BMI-SDS explained 16.8% of the
      degree of acanthosis nigricans (P<0.0001). Acanthosis nigricans thus may be a
      marker of insulin resistance and should be carefully looked for in obese
      adolescents.

PMID- 16302581
TI  - System-based strategy for the management of meconium aspiration syndrome: 198
      consecutive cases observations.
AB  - To evaluate whether the system-based strategy for management of meconium
      aspiration syndrome (MAS) could reduce the morbidity and mortality rate of MAS in
      our institute, a prospective consecutive clinical observation was conducted.
      System-based strategy including appropriately trained the relevant medical staff
      to familiar with neonatal resuscitation program, early surfactant replacement or
      lavage following with high-frequency ventilator (HFV) and/or inhaled nitric oxide
      (iNO). Outcome measurements were the morbidity and mortality rates of MAS. All
      infants of MAS in the study period were included except cases of congenital
      malformations or cyanotic congenital heart disease (CHD). Oxygen, nasal
      continuous positive airway pressure (CPAP), and intermittent mandatory
      ventilation (IMV) were applied as clinically indicated. Surfactant was used as
      replacement or lavage therapy for MAS infants whose oxygen index (OI) exceeded 20
      or value for AaDO2 exceeded 400 within 6 hours of age. High-frequency oscillator
      ventilation (HFO) was applied for infants of MAS that demonstrated intractable
      respiratory failure with conventional mechanical ventilation and 100% oxygen.
      Inhaled nitric oxide (iNO) was used with IMV or HFO for infants of persistent
      pulmonary hypertension (PPHN) when it was unresponsive to conventional therapy.
      Dexamethasone was prescribed in infants of severe hypotension that did not
      respond to dopamine and epinephrine. A series of 198 consecutive infants of MAS
      born in this hospital during 9 years were analyzed. There was no mortality.
      Fourteen infants developed PPHN, 11 had pneumothorax, 1 had pulmonary hemorrhage,
      2 had neurologic sequelae because of severe asphyxia, and 2 developed
      bronchopulmonary dysplasia. Our results indicated that appropriately trained
      relevant medical staff with neonatal resuscitation program to avoid complicated
      MAS and early surfactant replacement or lavage following with HFO and/or iNO
      could reduce the morbidity and mortality rate of MAS even without extracorporeal
      membrane oxygenation (ECMO).

PMID- 16302582
TI  - Epidemiology of respiratory syncytial virus in children with lower respiratory
      tract infection.
AB  - Respiratory syncytial virus (RSV) is the most frequent pathogen found in
      hospitalized young children with lower respiratory tract infection, and the virus
      is distributed worldwide. Respiratory distress and respiratory failure are caused
      by RSV in some severe cases. Its appearance always varies every year and depends
      on differences of latitudes, altitudes and climates. The purpose of this study
      was to investigate the epidemiology of hospitalized children from a hospital
      located in northern Taiwan with RSV induced lower respiratory tract infection.
      This study was conducted from January 2001 to December 2003, and the selected
      patients were children aged under five and diagnosed with lower respiratory tract
      infection. The means adopted in this study were analyses of clinical
      presentations and laboratory tests (including viral identification with either
      virus culture or RSV antigen rapid test from the nasopharyngeal aspirate). The
      results showed that 153 children were positive with RSV identification. These
      cases were diagnosed in clinical practice all year round, and its peak was in
      spring, especially in March and April. Thirteen percent of all RSV-infected
      children in this study presented as severe form with respiratory distress and a
      need of respiratory support. However, none of these cases died from this disease,
      and all cases recovered without long-term respiratory complication. We concluded
      that RSV infection was still a common pathogen for young children in northern
      Taiwan; in addition, March and April were regarded as peak months of epidemic.
      Patients aged under 12 months or suffered from underlying cardiopulmonary disease
      were at high risk of getting severe forms of RSV infection.

PMID- 16302583
TI  - Serial sonographic findings of lenticulostriate vasculopathy.
AB  - The vessels supplying basal ganglia and thalami are not usually detectable on the
      neurosonogram in the neonates. In recent studies, bright linear echogenesitis in
      these regions have been well decribed and were defined as lentriculostriate
      vasculopathy (LSV). These lesions suggested as a marker of a previous insult to
      the fetal or neonatal brain and the hemodynamics in the immature brain play an
      important role in its pathogenesis. In a period of 2 year and 5 months, we
      collected 39 cases of neonates and prematurities with LSV. These include 16 cases
      of premature babies, 16 cases of normal full-term neonates and 7 cases with
      perinatal insults. LSV was detected incidentally in most cases, distinctly
      different from the previous reports that LSV are linked with congenital anomaly,
      chromosomal anomaly, prematurity, perinatal insult or congenital infection, etc.
      There are early onset (< or = 7 days) LSV in 23 cases (59%) and late onset (>7
      days) in 16 cases (41%). 16 cases (41%) had total remission, 7 cases (18%) had
      partial remission, and 16 cases (41%) remained persistantly. Rare reports remined
      of the long term effect of LSV including tics, attention deficit hyperactive
      disorder and developmental delay. An isolated LSV generally has a good long term
      prognosis and a grave neurologic deficit may be mainly due to its associated
      brain damage.

PMID- 16302584
TI  - Comparison of right atrial pressure and central venous pressures measured at
      various anatomical locations in children.
AB  - PURPOSE: To compare the right atrial pressure to the central venous pressures
      measured at different points in spontaneously breathing children and try to find
      a formula to estimate right atrial pressure by central venous pressure
      measurement. METHODS: Fifty-one children, aged 5 +/- 4.7 years, who underwent
      right heart catheterization were studied. All patients were sedated and breathed
      naturally. The mean pressure was the electronic mean of nine heart beats
      calculated by Philips BC4000 digital angiographic system. Mean pressure of the
      right atrium was compared to those measured at the high superior vena cava (SVC),
      low SVC, high inferior vena cava (IVC) (T10-11), middle IVC (L1-2), low IVC (L3
      4), and iliac vein (L5-S1). RESULTS: Mean pressures of central veins were
      significantly higher than that of the right atrium (all p<0.01). Adjusted central
      venous pressures of SVC-0.5, high IVC-1.5, middle IVC-2, low IVC-2.5, and iliac
      vein-3 (mmHg) had a good agreement with the right atrial pressure. CONCLUSIONS:
      Central venous pressures are significantly higher than the right atrial pressure
      in spontaneously breathing children. Adjusted pressures of SVC-0.5, high IVC-1.5,
      middle IVC-2, low IVC-2.5, and iliac vein-3 (mmHg) can accurately reflect the
      right atrial pressure.

PMID- 16302585
TI  - Disseminated staphylococcal disease: report of one case.
AB  - Childhood septic arthritis is not only an uncommon presentation with
      polyarticular involvement, but is also rarely complicated with thromboembolism.
      We report a case of a 10-year-old boy who suffered multiple staphylococcal
      arthritis, deep vein thrombosis, pulmonary embolism, pericardial effusion and
      occlusion of the anterior parietal branch of the right middle cerebral artery.
      Oxacillin-sensitive Staphylococcus aureus was isolated from blood, synovial fluid
      and pericardial effusion. Intravenous six-week oxacillin combined with two-week
      gentamicin for eradicating the pathogen, arthrotomy for debridment and
      subcutaneous low-molecular-weight heparin for preventing further thromboembolism
      were administered during admission. In addition, surveys for immunodeficiency,
      connective tissue disease and hemostatic dysfunction produced negative findings.
      The patient was discharged with neither painful disability of involved joints nor
      neurological sequelae.

PMID- 16302586
TI  - Proximal weakness of lower limbs as the sole presentation of hyperthyroidism:
      report of one case.
AB  - Most children with acute or chronic flaccid limb weakness have a disorder of
      motor unit. However, it is very important to exclude cerebral or other upper
      motor neuron disorders before we approach such patients as pure muscle disorders.
      In general, neuropathy results in distal limb weakness, myopathy manifests with
      proximal weakness. There are exceptions, however. Accurate diagnosis in this wide
      array of disorders is dependent on a careful clinical assessment followed by the
      appropriate investigations. Here we report a 14-year-old girl who presented with
      progressive difficulty in rising up from the floor for one month. Neurological
      examination revealed an obese, clumsy but clear girl with stable vital signs. The
      muscle power of neck and upper limbs was normal. There was positive Gower sign,
      but the toe and heel gaits were acceptable. The initial blood work and
      motor/sensory nerve conduction velocity were unremarkable. Further study for
      thyroid function showed a hyperthyroid state. The proximal myopathy recovered
      soon after medical treatment. There were no other symptoms, and signs indicating
      hyperthyroidism and proximal myopathy of lower limbs was the isolated clinical
      feature. Hyperthyroid myopathy is common in hyperthyroidism, but is unusual as
      the sole presenting symptom.

PMID- 16302587
TI  - Transient hyperammonemia in a neonate.
AB  - Neonatal hyperammonemia is a medical emergency requiring a multidisciplinary
      teamwork for early recognition and early treatment. The causes of neonatal
      hyperammonemia vary. The transient hyperammonemia of the neonate (THAN) occurs
      mostly in premature babies, and the prognosis is usually better than for urea
      cycle disorders. Here we present a near-term premature male infant with THAN. He
      exhibited the symptoms during the first 36 hours of life and survived after
      continuous arteriovenous hemodiafiltration (CAVHD). Nutritional support and
      sodium benzoate were also given. The diagnosis was based on laboratory tests.
      Long-term follow-up of neurodevelopment was suggested.

PMID- 16302588
TI  - Feminizing adrenocortical adenoma presenting as heterosexual precocious puberty:
      report of one case.
AB  - We report on a case of a 2 2/12-year-old boy with heterosexual precocious puberty
      secondary to a feminizing adrenocortical adenoma. The boy, with no previous
      history of disease or treatment, presented with bilateral gynecomastia and pubic
      hair development (Tanner III breasts and Tanner II pubic hair). Plasma estradiol
      and testosterone were 410.9 pg/ml and 126.2 ng/dl respectively. Basal plasma LH
      and FSH levels were within the normal range. Bolus i.v. injection of GnRH showed
      unresponsiveness of LH and FSH. Abdominal echography and abdominal magnetic
      resonance imaging revealed a well-defined mass at the left suprarenal region
      (measuring 4.0 x 2.7 x 3.6 cm in size). After removal of the adrenal tumor, the
      estradiol and testosterone levels fell to normal in 2 weeks. The gynecomastia and
      pubic hair regressed with time. The pathology of the tumor showed compact pattern
      with polygonal cells containing moderate eosinophilic cytoplasm without mitotic
      figure. These findings were consistent with an adrenocortical adenoma secreting
      estradiol and testosterone as the cause of the patient's heterosexual precocious
      puberty.

PMID- 16302589
TI  - Partial androgen insensitivity syndrome with R840H mutation in androgen receptor:
      report of one case.
AB  - Androgen insensitivity syndrome (AIS) is the major cause of male
      pseudohermaphroditism. The severity of the disorders varies widely, ranging from
      the phenotypic women with female external genitalia in cases of complete AIS to
      the phenotype of ambiguous genitalia in partial androgen insensitivity syndrome
      (PAIS) and a rare group of phenotypic normal males with azoospermia. Here, we
      report an infant of PAIS with a missense mutation at position 2881 (G-->A) in
      exon 7, encoding substitution of histidine for arginine at codon 840 of the
      androgen receptor (AR) gene. Both the biochemical and molecular studies are
      presented. Establishing the diagnosis of PAIS is very important for gender
      assignment to an infant of ambiguous genitalia. The molecular analysis will
      facilitate genetic counselling to the maternal side relatives for carrier
      detection and prenatal diagnosis.

PMID- 16302590
TI  - Streptococcal toxic shock syndrome with initial manifestation of abdominal pain
      and cholecystitis.
AB  - Streptococcal toxic shock syndrome with the initial manifestation of abdominal
      pain and cholecystitis is rare. We report the case of a 10-year-old boy who
      presented with abdominal pain, cholecystitis and shock initially. Acute
      respiratory distress syndrome, renal and hepatic insufficiency and disseminated
      intravascular coagulation developed soon after admission. Skin rash and
      desquamation were found subsequently during the recovery phase. The blood and
      sputum cultures were sterile. Acute and convalescent plasma from the patient
      showed increased anti-streptolysin O titer (ASLO titer). Measurement of the ASLO
      titer on Day 11 after the onset of disease had an ASLO titer of 242 IU/ml (N
      Latex ASL, Dade Behring Marburg GmbH, USA), and the ASLO titer on Day 21 after
      the onset of disease showed an increase to 875 IU/ml. These clinical findings and
      the plasma analysis were consistent with streptococcal toxic shock syndrome.

PMID- 16302591
TI  - Caries experience associated with attention-deficit/hyperactivity disorder.
AB  - The purpose of this cross-sectional study was to examine whether children with
      attention-deficit/hyperactivity disorder (ADHD) had a total caries experience
      that was equivalent to children without the disorder. METHODS: The test sample
      included children ages 6 to 10 years old diagnosed with ADHD by physicians at
      Duke University Medical Center. The control group also included healthy children
      6 to 10 years old without the diagnosis of ADHD. A visual dental exam for caries
      was performed and a sample of whole, unstimulated saliva was collected. The
      parent/guardian of each participant completed a health/medication history and a
      questionnaire concerning the child's oral health and habits, daily routine, and
      demographic information. RESULTS: Wilcoxon and chi-square tests showed that
      children with ADHD have significantly more enamel caries in the primary and
      permanent dentitions and a significantly higher prevalence of total caries
      experience when compared to controls. There was no significant difference in
      whole saliva production between the ADHD children and the controls. CONCLUSIONS:
      Dentists should be aware that children with ADHD are at higher risk for caries.

PMID- 16302592
TI  - Plaque and salivary pH changes after consumption of fresh fruit juices.
AB  - The concept of health has prevailed for centuries and the dietary habits are
      apparently changing with modernization. "Healthy eating" is now perceived to be
      important. The desirability of a healthful lifestyle has led to an increased
      consumption of juices. Drinking large amount of fruit juice is frequently
      practiced these days and the consumption of these juices is further modified with
      behavioral habits such as swishing and frothing the drinks around the mouth,
      sucking frozen fruit juices, use of feeder cups at bed time etc. Hence this study
      was conducted to find the acidogenic potential of the commonly consumed fresh
      fruit juices (Grapes, orange, and pineapple) and the juices stored at various
      temperatures (room temperature, refrigerator and freezer) on the plaque and
      saliva at various intervals. It was observed that grape juice was more acidogenic
      compared to orange and pineapple juice. Frozen fruit juices caused a greater drop
      in plaque and salivary pH followed by the refrigerated juice.

PMID- 16302593
TI  - Mouthwash ingestion by preschool children.
AB  - Even though fluoride provides a significant contribution in dental caries
      prevention, it is known that its random employment may lead to enamel alterations
      such as dental fluorosis, besides the possibility of severe systemic alterations.
      The aim of this study was to evaluate the ingestion of mouthwashes administered
      to preschool children. It was concluded that parents and teachers of young
      children must be very careful during the accomplishment of educational programs
      comprising fluoridated mouthwashes, because of the high possibility of ingestion.

PMID- 16302594
TI  - Sex identification from exfoliated primary teeth--a PCR study.
AB  - Teeth endure postmortem degradation and extreme changes in ambient temperature
      and pressure better than most human tissues. In the present day scenario the
      growing number of crime against children in the form of battering,
      physical/sexual abuse, abduction and kidnapping, the use of exfoliated primary
      teeth, become many times the only evidence available at the crime scene. Despite
      exposure of the body to burial, mutilation, explosion or incineration, it is
      usually possible to extract DNA from pulp tissue of tooth with sufficient quality
      and quantity. Hence the present study was undertaken to find out the sex of a
      child from exfoliated/extracted deciduous teeth using a Polymerase Chain reaction
      (PCR) based analysis. Tooth samples were stored in room temperature after double
      coding for various periods. Dental pulp tissue was collected from each sample and
      DNA was isolated by proteinase-k digestion and phenol chloroform extraction
      methods. PCR amplification was done with two sets of oligonucleiotide primers.
      Amplification of X (131bp) and Y-specific sequences (172bp) in males and that of
      the X-specific sequence in females was observed and compared with the template
      DNA showing male and female controls. Determination of sexes of all freshly
      collected samples within 24 hours and after 1 month of extraction respectively
      gave 100% result. However, PCR was not found to be an effective method for sex
      determination after 6 months post extraction.

PMID- 16302595
TI  - Effect of oral anticipatory guidance on oral health and oral hygiene practices in
      preschool children.
AB  - Thirty children (6 to 18 months), enrolled in a dental program since birth, make
      up the intervention group. Control group consisted of thirty children who were of
      similar age and gender but had never been to a dental office. The presence of
      visible dental plaque and the performance of oral hygiene differed statistically
      between both groups. The dental program was effective in reducing visible dental
      plaque, and in establishing oral health habits among parents and young children.

PMID- 16302596
TI  - A modified technique on the reattachment of permanent tooth fragments following
      dental trauma. Case report.
AB  - Fractured anterior teeth can be restored by adhesive bonding of the fractured
      fragment to the remaining tooth structure. One of the major challenges for the
      practitioner treating traumatized anterior teeth with immediate fragment
      reattachment is disguising the fracture line, through the correct use of masking
      and restorative resins to make the restorations imperceptible to the eye as well
      as improve the retention of the restoration. This paper discusses a modified
      technique for reattaching a permanent tooth fragment following dental trauma. The
      initial procedure involved simple reattachment using light cured composite resin
      between the fragment and the remnant part of the tooth, without additional
      preparation. The surplus resin was spread across it in an attempt to optimize
      marginal seal and improve the aesthetics of the restoration. Finally, after
      taking into account the occlusion, the lingual surfaces of the teeth were
      veneered with microfilled composite to improve the retention of the reattached
      fragments.

PMID- 16302597
TI  - An assessment of a new reminder therapy technique for ceasing digit sucking
      habits in children.
AB  - Twenty-one digit-sucker children aged 4-12 old years participated in the
      assessment of a new reminder therapy technique called "long sleeve sleeping gown
      ". The result of this study indicated that fifteen children (71.4%) out of 21
      were able to stop digit-sucking habits after the application of long sleeve's
      gown during child's bedtime for 6 weeks. The children who failed to cease this
      digit-sucking habit (28.6%) were found to not accept to complete the trial period
      or their mothers thought that they were too young to stop the habit. Among the
      success group no child was reported to return to digit-sucking 3 months after
      implementation of long sleeves gown.

PMID- 16302598
TI  - Flowable resin used as a sealant in molars affected by dental fluorosis: a
      comparative study.
AB  - The decline in prevalence and incidence of dental caries in developed countries
      over the last two decades is considered to be due mainly to the widespread use of
      fluoride in different forms, but simultaneously with decline in caries, an
      increase in dental fluorosis has been reported. The aim of this study was to
      compare the Conventional Sealant Technique (CST) and Enameloplasty Sealant
      Technique (EST) using a flowable resin as sealant in molars affected by dental
      fluorosis. A total of 40 extracted third molars affected by dental fluorosis were
      divided at random into two groups of 20 teeth each, and Tetric Flow resin was
      used as sealant. All teeth were studied for lateral adaptation and resin
      penetration by direct and indirect techniques; all samples were replicated in
      epoxy resin and were evaluated with Scanning Electron Microscopy (SEM). The
      results demonstrated that EST allowed a deeper sealant penetration and a superior
      sealant adaptation than CST, both in direct and indirect evaluations by SEM. The
      most important variables being penetration-interface and penetration depth both
      being statistically significant (p<0.05). The CST did not flow into the bottom of
      the fissures, leaving spaces that can favor the fracture of the material and
      initiate the process of dental caries. We conclude that a flowable ceromer is an
      excellent material alternative to be used as sealant and that EST is quite
      necessary in molars affected by dental fluorosis, the combination of both being a
      reliable method to be used as primary prevention approach of dental caries in
      endemic areas of dental fluorosis.

PMID- 16302599
TI  - Composite resin bond strength to primary dentin prepared with Er, Cr:YSSG laser.
AB  - This in vitro study evaluated the shear bond strength of a hybrid composite resin
      bonded to primary dentin prepared with an Er, Cr:YSGG hydrokinetic laser compared
      to conventional bur prepared primary dentin. The results suggest that primary
      dentin surfaces treated with the Er, Cr:YSGG laser, with or without etching, may
      provide comparable or increased composite resin bond strengths depending upon
      bonding agent used.

PMID- 16302600
TI  - Colony forming unit levels of salivary Lactobacilli and Streptococcus mutans in
      orthodontic patients.
AB  - The purpose of this study was to compare the levels of Lactobacilli (LB) and
      Streptococcus mutans (SM) colony forming units (CFU) in the saliva of subjects
      before and after orthodontic appliance placement. This was a controlled,
      prospective two-group, two-measurement, clinical trial performed on 64 study
      patients, 12-15 years old. Subjects in the experimental group were sampled for LB
      and SM in stimulated saliva collected on the same day but prior to band and
      bracket placement. The subjects in the control group were sampled on their first
      screening appointment two months prior to band and bracket placement. The second
      samples of LB and SM were taken from the experimental and control groups after
      two months. Saliva was transferred to a selective agar carrier and incubated for
      48 hours at 37 degrees C / 99 degrees F. LB and SM colonies forming units were
      compared with standard densities. The experimental group wearing orthodontic
      appliances had significantly higher mean LB CFU counts than the control group at
      the 2 month follow-up (3.25 vs. 2.57, p = 0.0036). The two groups, however, did
      not show any difference in mean SM CFU counts at the 2 month follow-up (3.0 vs.
      3.1, p = 0.66). The results of this study showed that a higher number of CFUs of
      LB were associated with the group wearing orthodontic appliances after two months
      and may play a role in the increased levels of plaque seen in many orthodontic
      patients.

PMID- 16302601
TI  - Ectodermal dysplasia--an unusual dental presentation.
AB  - Ectodermal dysplasia (ED) is a rare group of disorders affecting the hair, teeth,
      nails and sweat glands to a variable degree. There is a wide range of clinical
      presentation of ED. Missing teeth or abnormal tooth form may be the first
      indicator of the presence of the disorder. There is typically hypodontia with
      microdontia. We present an unusual case of ED with severe hypodontia and
      macrodontia affecting all first permanent molar teeth. We also consider the
      classification and presentation of this disorder.

PMID- 16302602
TI  - Oral-clinical findings and management of epidermolysis bullosa.
AB  - Epidermolysis bullosa (EB) is a diverse group of disorders that have as a common
      feature blister formation with tissue occuring at variable depths in the skin
      and/or mucosa. This article reports two cases of EB and review oral-clinical
      findings of the EB types and approaches for managing the oral-clinical
      manifestations. While systemic treatment remains primarily palliative, it is
      possible to prevent destruction and subsequent loss of the dentition through
      appropriate interventions and dental therapy.

PMID- 16302603
TI  - Focal dermal hypoplasia: oral and dental findings.
AB  - Focal Dermal Hypoplasia/Goltz Gorlin syndrome is a rare syndrome characterized by
      widespread dysplasia affecting tissues of mesodermal and ectodermal origin with
      cutaneous, osseous, ocular, oral and dental defects. Enamel hypoplasia is the
      most commonly reported dental manifestation and has recently been described as a
      possible manifestation of Lyonisation. This article reviews the reported dental
      findings and reports a new case with typical findings of focal dermal hypoplasia,
      which has been under review on our department for 10 years. It discusses the
      differential diagnosis as well as newer concepts of aetiology and pathogenesis in
      relation to dental anomalies. Enamel hypoplasia may make plaque control
      difficult, resulting in generalized gingivitis. Hand anomalies may limit
      dexterity and exacerbate this. From the dental standpoint we emphasize the
      implementation of timely preventive and/or therapeutic strategies. Since there
      are periods of exacerbation during the course of this syndrome, regular
      surveillance from an early age with the frequency of visits increasing during and
      after adolescence is indicated. The role of the dentist in improving aesthetics
      and function can have tremendous psychological impact to enhance self-esteem of
      such patients.

PMID- 16302604
TI  - Atypical Hallerman-Streif syndrome: a case report.
AB  - Hallerman Streif syndrome is a rare congenital disorder characterized by
      dyscephaly, dental anomalies, proportionate nazism, hypotrichosis, cutaneous
      atrophy limited to the head, bilateral congenital cataracts and bilateral
      microphthalmia. Despite the marked craniofacial characteristics and oral
      findings, a relative lack of reports in the dental literature has been noted. In
      this article, a case of a 8 year old boy with dental problems is described.

PMID- 16302605
TI  - Clinical features, dental findings and dental care management in osteogenesis
      imperfecta.
AB  - This article reports the case of a child diagnosed with type III osteogenesis
      imperfecta, assessing the clinical features observed, with emphasis on the
      craniofacial, oral and dental findings, and describes the dental care management
      rendered for this special needs patient. The issues addressed and discussed
      throughout the paper shows that, as far as the oral health professionals are
      familiarized with the disease-specific clinical manifestations and the possible
      implications of this condition, there are no hindrances for a successful, high
      quality dental and behavioural management.

PMID- 16302606
TI  - Axenfeld-Rieger syndrome: report on dental and craniofacial findings.
AB  - Axenfeld-Rieger syndrome is a rare autosomal dominant disorder characterized by
      various ocular and extraocular malformations. Dental abnormalities are considered
      as definitive features for the diagnosis and differentiation of Rieger syndrome
      from other anterior chamber of the eye malformations. A case of Rieger syndrome
      with distinct dental and craniofacial anomalies is described. Significant cranio
      dento-facial findings that have been observed are, teeth with short and
      dilacerated roots, hyperplastic frenums and underdeveloped maxilla. There was an
      anterior crossbite, bilateral posterior open-bite and moderate to severe anterior
      crowding.

PMID- 16302607
TI  - Oral manifestations of HIV infection in 36 Nigerian children.
AB  - Oral manifestations of HIV/AIDS are early and common clinical indicators of HIV
      infection. There has been no report on the clinical prevalence of oral lesions
      associated with HIV infection in children in sub-Saharan Africa. We report the
      findings of a cross sectional study of 36 Nigerian children seen at the
      Pediatrics Infectious Disease Clinic of the AIDS Prevention Initiative in Nigeria
      (APIN), Jos University Teaching Hospital (JUTH) Jos, Nigeria.

PMID- 16302608
TI  - Endoscopic fourth ventricular aqueductoplasty.

PMID- 16302609
TI  - Endoscopic cerebral aqueductoplasty: a trans-fourth ventricle approach.
AB  - OBJECT: Advances in endoscopic technology have afforded the neurosurgeon new
      avenues in the treatment of hydrocephalus, rendering many patients independent of
      shunts, thus averting shunt complications and failure. Cerebral aqueductoplasty
      has gained popularity as an effective treatment for membranous and short-segment
      stenoses of the sylvian aqueduct. Traditionally, this procedure has been
      performed via a coronal approach, passing through the lateral ventricle, foramen
      of Monro, and third ventricle into the aqueduct. The authors report on the
      success of a novel technique for this operation, in which they use a suboccipital
      foramen magnum trans-fourth ventricle approach. METHODS: A retrospective chart
      review was performed to document the success of cerebral aqueductoplasty
      procedures via the foramen magnum trans-fourth ventricle approach in patients who
      had membranous or short-segment stenosis of the cerebral aqueduct. Nine patients
      underwent 11 cerebral aqueductoplasty procedures. At a mean of 21 months of
      postoperative follow up, all patients demonstrated resolution of their
      preoperative symptoms. The only surgical complication was transient vertical
      diplopia or upgaze weakness in two patients. There was no permanent morbidity.
      Recurrent aqueductal stenosis developed in one patient twice, requiring the
      placement of an aqueductal stent via the same approach. CONCLUSIONS: The authors
      state that in their experience, performing cerebral aqueductoplasty via the
      foramen magnum trans-fourth ventricle approach is both effective and safe. They
      advocate the use of this technique, if performed by an experienced
      neuroendoscopist, for select cases involving membranous or short-segment stenosis
      of the cerebral aqueduct, a trapped fourth ventricle, or aqueductal stent
      placement.

PMID- 16302610
TI  - Endoscopic third ventriculostomy: an outcome analysis of primary cases and
      procedures performed after ventriculoperitoneal shunt malfunction.
AB  - OBJECT: The authors analyzed the role of endoscopic third ventriculostomy (ETV)
      as a primary treatment for hydrocephalus and also as an alternative to shunt
      revision for malfunctioning and infected ventriculoperitoneal (VP) shunts.
      METHODS: A retrospective analysis of clinical notes, operation records, and
      magnetic resonance imaging procedures before and after ventriculostomy was
      performed to determine the success or failure of ETVs in 170 patients who
      underwent a primary ETV and in 63 patients who underwent an ETV for shunt
      malfunction (secondary ETV). The patients' data were derived from an endoscopy
      database inaugurated in 1998. Of the 63 patients with shunt malfunctions, 49
      patients (78%) had mechanical malfunction only and 14 patients (22%) had both
      infection and malfunction. Seventy-four percent (126 of 170) of patients in the
      primary ETV group and 70% (44 of 63) of patients in the secondary ETV had a
      successful outcome at the time of analysis. The success rate for ETVs in cases
      involving a mechanical shunt malfunction alone was 67% (33 of 49) compared with
      79% (11 of 14) in those cases involving an infected shunt. The origin of the
      hydrocephalus in the primary and shunt malfunction groups was evaluated as a
      factor contributing to the success of the ETV. In the primary group, patients
      with a history of intraventricular hemorrhage (IVH) and meningitis as a cause for
      hydrocephalus had a poor rate of success after the ETV--27% (four of 15) and 0%
      (none of two), respectively. This pattern was not seen in the series involving
      shunt malfunction after the ETV, with 71% (five of seven) and 75% (three of four)
      of cases having a hydrocephalus origin of IVH and meningitis, respectively, in
      which a successful outcome was attained. A two-way mixed-model analysis of
      variance yielded a significant effect for origin (p = 0.011), a significant
      interaction between group and origin (p = 0.028), and a marginally nonsignificant
      effect of group (p = 0.0686). More than 95% of failures were evident within 1
      month of the ETV in both groups. Complications were minimal in both groups, and
      there were no procedure-related deaths. CONCLUSIONS: An ETV is a safe procedure
      with few complications and a high success rate in both primary and secondary
      groups. An ETV to address shunt malfunction, unlike a primary ETV, is not
      particularly origin specific. A bonus is its success in dealing with infected
      shunts. Most failures will be evident early, but long-term follow up is vital.

PMID- 16302611
TI  - Long-term outcome after surgical treatment of temporal lobe epilepsy in children.
AB  - OBJECT: Surgery is an accepted treatment for carefully selected patients with
      focal epilepsy. In the present study, the authors assessed clinical and surgery
      related data obtained in a large series of children suffering from intractable
      temporal lobe epilepsy (TLE). METHODS: Etiological, pathological, and clinical
      features of possible prognostic significance were studied in 109 children who
      underwent surgery for TLE at the Montreal Neurological Institute and Hospital and
      the Montreal Children's Hospital between 1985 and 2000. The mean age of patients
      at seizure onset was 5.5 years and the duration of epilepsy ranged from 0.1 to
      17.6 years. Preoperative magnetic resonance imaging revealed mesial sclerosis in
      51 patients, a mass lesion in 45, and no visible abnormalities in 12. In six
      patients invasive monitoring was required. Cortical amygdalohippocampectomy was
      performed in 72% of patients, whereas 20% underwent transcortical selective
      amygdalohippocampectomy. In 23 patients a second surgical intervention was
      necessary. Low-grade tumors were found in 35% and mesial sclerosis was confirmed
      on pathological evaluation in 45%. Outcome was excellent (seizure free or > 90%
      reduction) in 94 patients (86%). The patients were followed prospectively for a
      median of 10.9 years (range 5-20.2 years). There were no permanent neurological
      complications and no deaths. CONCLUSIONS: Successful postsurgical outcomes,
      especially in patients treated for mesial temporal lobe sclerosis and lesion
      related epilepsies, can be obtained in pediatric patients suffering minimal
      complications. Unfavorable outcomes are most likely to occur when epileptiform
      discharges are bitemporal or multifocal in distribution and in cases involving
      incomplete resection of mesiotemporal structures.

PMID- 16302612
TI  - Single-center experience with pediatric Cushing's disease.
AB  - OBJECT: Despite ongoing advances in surgical and radiotherapeutic techniques,
      pediatric Cushing's disease remains a diagnostic and therapeutic challenge. The
      authors report on the results of a single-center retrospective review of 33
      pediatric patients with Cushing's disease, providing details with respect to
      clinical presentation, diagnostic evaluation, therapeutic course, complications,
      and outcomes. METHODS: There were 17 female and 16 male patients whose mean age
      was 13 years (range 5-19 years) in whom a diagnosis of Cushing's disease was
      based on clinical and biochemical criteria. Typical symptoms included weight gain
      (91%), prepubertal growth delay (83%), round facies (61%), hirsutism (58%),
      headache (45%), abdominal striae (42%), acne (33%), amenorrhea (24%), and
      hypertension (24%). In 67% of the cases, preoperative magnetic resonance images
      revealed a pituitary lesion and in 82% of the cases the imaging studies
      effectively predicted lateralization. Inferior petrosal sinus sampling was
      performed in seven patients (21%), and in all of these cases lateralization was
      100% reliable. Fifty-five percent underwent selective adenomectomies and 45%
      underwent subtotal hypophysectomies. Complications included one case of diabetes
      insipidus, one of persistent hypocortisolemia necessitating prolonged
      glucocorticoid replacement therapy, and one minor vascular injury that did not
      necessitate postoperative management modification or cause sequelae. There were
      no surgery-related deaths and no cases of postoperative cerebrospinal fluid
      leakage or meningitis. During a mean follow-up period of 44 months, clinical
      remission was ultimately achieved in 91% of patients: 76% after transsphenoidal
      surgery alone and an additional 15% after adjuvant radiosurgery and/or
      adrenalectomy following surgical failure. Three patients (12%) experienced
      disease recurrence and underwent a second surgical procedure at 18, 81, and 92
      months, respectively; based on clinical and biochemical criteria a second
      remission was achieved in all. Three patients (9%) remain with persistent
      disease. CONCLUSIONS: Pediatric Cushing's disease is a rare condition, often
      requiring a multidisciplinary diagnostic and a multimodal therapeutic approach
      for successful long-term remission.

PMID- 16302613
TI  - Influence of tumor location on the presentation and evolution of
      craniopharyngiomas.
AB  - OBJECT: This study was performed to optimize the management of
      craniopharyngiomas, particularly by identifying factors predicting weight changes
      to prevent obesity. METHODS: A series of 35 patients who had undergone surgery at
      a mean age of 7.4 +/- 3.7 years (standard deviation [SD]) and had been followed
      up until 14.9 +/- 5 years of age by the same endocrinologist were assigned to one
      of three groups according to their hypothalamic involvement: Group 1 (10
      patients) had no involvement, Group 2 (eight patients) had compression without
      involvement, and Group 3 (17 patients) had severe involvement. Abnormal height
      and/or weight evolution indicated the craniopharyngioma in only 17% of the
      patients, although these elements were present at diagnosis in 85%. Before
      surgery, 85% of the patients lacked growth hormone, 24% lacked thyroid
      stimulating hormone, 15% lacked adrenocorticotropin hormone, and 12% lacked
      antidiuretic hormone. All had complete hypothalamic-pituitary deficiencies after
      surgery. The body mass index (BMI) before surgery (mean SD 1.1 +/- 1.6) was
      positively correlated with BMI 1 year after surgery (mean SD 3.1 +/- 2), which
      correlated with the BMI at the last evaluation (mean SD 3.1 +/- 1.9; p < 0.0001
      for both). Before surgery, patients in Group 3 had a greater BMI than did Group 1
      (p < 0.02). The BMI of Group 1 patients did not change, but those of Groups 2 and
      3 patients increased during the 1st year after surgery (p < 0.02 and p = 0.0003,
      respectively), with no further change. The changes occurred mainly during the
      first 3 months after surgery in Group 1, during the first 6 months in Group 2,
      and throughout the year in Group 3. CONCLUSIONS: The degree of hypothalamic
      involvement by the craniopharyngioma determines the presentation and predicts
      weight changes after surgery.

PMID- 16302614
TI  - Chemical analysis of fluid obtained from intracranial arachnoid cysts in
      pediatric patients.
AB  - OBJECT: The authors analyzed the chemical composition of intracranial arachnoid
      cyst fluid to gain greater understanding of potential causes of cyst growth.
      METHODS: The authors studied 54 pediatric patients who underwent craniotomies for
      arachnoid cyst fenestration. Cyst fluid was analyzed and results were compared
      with expected values (EVs) for cerebrospinal fluid (CSF). The arachnoid cyst
      fluid values were as follows: protein (median 37 mg/dl, mean 178.2 mg/dl, and EV
      25.6 mg/dl), osmolality (median 284 mOsm/kg, mean 285.5 mOsm/kg, and EV 287.2
      mOsm/kg), potassium (median 2.6 mEq/L, mean 2.68 mEq/L, and EV 2.88 mEq/L),
      sodium (median 140 mEq/L, mean 142.2 mEq/L, and EV 143.3 mEq/L), and chloride
      (median 122 mEq/L, mean 120.77 mEq/L, and EV 120.3 mEq/L). Median glucose was 51
      mg/dl (range 26-98 mg/dl). The median white blood cell count in cyst fluid was
      1/mm3, and the median red blood cell (RBC) count was 1.5/mm3. All Gram stains and
      cultures were negative. No statistically significant correlations were found
      between arachnoid cyst fluid protein level and elevated RBC count, patient age,
      or the subsequent need for a shunt. Elevated RBC count in cyst fluid was also not
      associated with the subsequent need for a shunt. CONCLUSIONS: Fluid from
      arachnoid cysts has a chemical composition similar to that of CSF, but some of
      them have significantly elevated protein levels. The authors hypothesize that
      elevated protein content may contribute to arachnoid cyst expansion in some
      patients.

PMID- 16302615
TI  - Risk factors for postoperative ischemic complications in patients with moyamoya
      disease.
AB  - OBJECT: The aim of this study was to determine the risk factors associated with
      the development of postoperative ischemic complications after surgical
      revascularization used to treat pediatric patients with ischemic moyamoya
      disease. METHODS: The clinical, imaging, and perioperative data from 170
      procedures in 90 children who underwent indirect revascularization surgery were
      retrospectively reviewed. To clarify the risk factors, cases with identified
      ischemic complications and those without such events were compared. For this
      study, a postoperative ischemic complication was defined as a newly developed
      infarction within 2 weeks after surgery, which was confirmed by follow-up imaging
      studies. CONCLUSIONS: The higher ischemic risks from surgical treatment should be
      considered for patients with moyamoya disease who are younger than 3 years of age
      and have a preoperative cerebral infarction. It is also recommended that the
      revascularization surgery be delayed for at least 6 weeks after the development
      of the previous cerebral infarction.

PMID- 16302616
TI  - Headache in pediatric moyamoya disease: review of 204 consecutive cases.
AB  - OBJECT: Patients with moyamoya disease complain of headache before surgery, after
      surgery, or in both periods. To clarify the pathophysiological features of these
      headaches which are one of the major symptoms in moyamoya disease after indirect
      bypass surgery, the authors reviewed data obtained in patients with moyamoya
      disease who underwent such surgery at their institute. METHODS: The authors
      surveyed 204 children with moyamoya disease younger than 17 years of age who
      underwent indirect bypass surgery consecutively between 1988 and 2000. If
      headache and associated symptoms disturbed their daily activity, required rest
      and/or medication, and occurred at least once a month, the headache was regarded
      as significant and the patient was included in the study. A postoperative
      headache was defined as the presence of significant headache 12 months after the
      operation or later. Preoperative headache was documented in 44 patients.
      Postoperative headache was observed in 63% (28 of 44) of the patients with
      preoperative headache and in 6.3% (10 of 160) of those without preoperative
      headache. Aggravation on postoperative magnetic resonance images or single-photon
      emission computerized tomography scans did not correlate with this symptom (p =
      0.729 and 0.203, respectively). The clinical course had the following features:
      1) a coexisting stage of headache and transient ischemic attack; 2) a second
      stage of headache only; and 3) a final stage of improvement or disappearance of
      headache. CONCLUSIONS: The authors demonstrated that headaches can persist or
      develop after indirect bypass surgery despite successful prevention of cerebral
      ischemia. In addition to decreased cerebral blood flow, progressive recruitment
      and redistribution of blood flow should be considered as a cause of headaches in
      patients with moyamoya disease.

PMID- 16302617
TI  - Terminal myelocystocele.
AB  - OBJECT: The authors describe the cases of eight patients with terminal
      myelocystoceles and report on their initial diagnoses, neuroimaging findings,
      surgical procedures, and clinical follow-up examinations. METHODS: There were
      seven girls and one boy. The initial age at diagnosis ranged from prenatal age
      (determined by imaging) to 14 years. Operative correction was performed from 6
      weeks to 14 years of age. One patient presented with a large prevertebral
      (intraabdominal) meningocele. Four patients have associated abdominal wall
      defects and are significantly handicapped. Two are wheelchair bound and the other
      two ambulate with prosthetic devices; all are incontinent. The four patients
      without abdominal wall defects are fully ambulatory; one wears an ankle-foot
      orthosis. One patient has normal bowel and bladder functions, and the other three
      require intermittent clean catheterization. No patient to date has had clinical
      evidence of retethering, although a low-set conus medullaris and residual lipoma
      were visible on postoperative neuroimaging. No patient in this series had
      hydrocephalus or Chiari malformation. CONCLUSIONS: It is concluded that patients
      with myelocystoceles without abdominal wall defects have a favorable neurological
      outcome when compared with those having ventral wall defects.

PMID- 16302618
TI  - Identification of phenotypic neural stem cells in a pediatric astroblastoma.
AB  - OBJECT: The goal of this study was to illustrate the findings of a significant
      subpopulation of cells within a pediatric astroblastoma that have the specific
      cell surface phenotype found on known human neural stem cells. METHODS: Cells
      with a cell surface marker profile characteristic of human neural stem cells were
      isolated using fluorescence-activated cell sorting from a mostly nonmitotic
      astroblastoma removed from the brain of an 11-year-old girl. An unusually high
      proportion (24%) of the cells were CD133 positive and CD24, CD34, and CD45
      negative (CD133(+)CD24(-)CD34(-)CD45(-) cells), the phenotypic antigenic pattern
      associated with neural stem cells; very few CD133-positive cells were not also
      CD24, CD34, and CD45 negative. Some cells (12%) were CD34 positive, indicating
      the presence within the tumor of hematopoietic stem cells. Cells formed
      cytospheres that resembled neurospheres when seeded into stem cell media and
      coexpressed beta-tubulin and glial fibrillary acidic protein (GFAP) but did not
      express the oligodendrocyte marker O4. Cell proliferation was demonstrated by
      incorporation of bromodeoxyuridine. The cells lost their capacity for self
      renewal in vitro after four to six passages, although they continued to coexpress
      beta-tubulin and GFAP. The cells did not differentiate into neurons or astrocytes
      when placed in differentiation medium. CONCLUSIONS: Although this astroblastoma
      contained a high proportion of phenotypic neural stemlike cells, the cells had
      limited proliferative capacity and multipotency. Their role in astroblastoma
      formation and growth is unknown.

PMID- 16302620
TI  - Pediatric orbital multifocal cavernous hemangiomas associated with bilateral
      arachnoid cysts of the middle cranial fossa. Case report and review of the
      literature.
AB  - Cavernous hemangiomas of the orbit are benign vascular growths that commonly
      occur in adults and account for 6% of all intraorbital tumors. Multifocal
      intraorbital cavernous hemangiomas are quite rare. The reported incidence of
      arachnoid cysts accounts for only 1% of lesions that occupy intracranial space,
      and they are nearly always sporadic and single. So far, the authors have not
      encountered any study reporting the coexistence of bilateral arachnoid cysts of
      the middle cranial fossa and orbital multifocal cavernous hemangiomas. In this
      report, they describe a 10-year-old boy with such a hemangioma that included the
      eyelid, conjunctiva, and retrobulbar space. His was the first case of a
      surgically treated pediatric orbital multifocal cavernous hemangioma associated
      with bilateral arachnoid cysts of the middle cranial fossa. An association
      between arachnoid cysts, intracranial cavernous malformations, and bilateral
      arachnoid cysts and metabolic disorders has been reported. The authors report on
      the coexistence of orbital multifocal cavernous hemangiomas and bilateral
      arachnoid cysts of the middle cranial fossa. Based on these observations, they
      believe that all patients with bilateral temporal arachnoid cysts should be
      screened for genetic disorders. In addition, the possibility of orbital cavernous
      malformations should be kept in mind for the follow-up period, and patients
      should be evaluated for possible symptoms of this condition.

PMID- 16302619
TI  - A congenital brain tumor associated with assisted in vitro fertilization. Case
      report.
AB  - In this report the authors describe the clinical features of a rare neonatal
      anaplastic astrocytoma in the setting of in vitro fertilization (IVF). The infant
      had been conceived using IVF and was born full term to a 29-year-old prima
      gravida mother. At birth, the baby boy was irritable and demonstrated poor
      feeding. Cranial ultrasonography and magnetic resonance imaging revealed an
      echogenic mass in the left hemisphere with midline shift and hydrocephalus.
      Grosstotal resection of an anaplastic astrocytoma was followed by chemotherapy
      with temozolomide and vincristine. Previous cases of neonatal brain tumors
      occurring in the setting of assisted reproduction are reviewed. A possible
      association between IVF and congenital neuroepithelial tumors is highlighted.

PMID- 16302621
TI  - Delayed intracranial hypertension and cerebellar tonsillar necrosis associated
      with a depressed occipital skull fracture compressing the superior sagittal
      sinus. Case report.
AB  - Depressed skull fractures overlying the major venous sinus are often managed
      nonoperatively because of the high associated risks of surgery in these
      locations. In the presence of clinical and radiographic evidence of sinus
      occlusion, however, surgical therapy may be necessary. The authors present the
      case of a 9-year-old boy with a depressed skull fracture overlying the posterior
      third of the superior sagittal sinus. After initial conservative treatment,
      delayed signs of intracranial hypertension and a symptomatic tonsillar herniation
      with tonsillar necrosis developed. Possible causes as well as diagnostic and
      treatment options are reviewed.

PMID- 16302622
TI  - Endovascular treatment of spinal arteriovenous fistula in a young child with
      hereditary hemorrhagic telangiectasia. Case report.
AB  - Hereditary hemorrhagic telangiectasia ([HHT] or Osler-Weber-Rendu syndrome) can
      manifest as sudden onset of epistaxis or neurological deficit in a child with
      characteristic mucocutaneous telangiectasias or as an asymptomatic bruit with or
      without overlying cutaneous vascular lesions. The authors present a case study of
      a pediatric patient with HHT in whom a screening computerized tomography (CT)
      scan of the chest revealed an asymptomatic arteriovenous malformation (AVM) of
      the spine. An 18-month-old child with a strong family history of HHT, including
      fatal central nervous system (CNS) hemorrhage and pulmonary AVMs, presented with
      a cutaneous telangiectasia of the pinna. The child was subsequently screened for
      potentially morbid pulmonary and CNS AVMs by using chest CT scanning and brain
      magnetic resonance (MR) imaging. A spinal MR image revealed a perimedullary macro
      AVF (MAVF) resulting in a large venous varix within the parenchyma of the
      thoracic spinal cord. A transarterial embolization of the fistula was performed
      using N-butyl cyanoacrylate and ethiodol. Postembolization angiography confirmed
      obliteration of the fistula, and MR imaging revealed thrombosis and reduction in
      size of the venous varix. There were no neurological sequelae due to the
      treatment. In families with HHT and a high risk of sudden severe morbidity or
      death from undisclosed pulmonary or CNS AVMs, screening chest CT scanning and CNS
      MR imaging should be considered. Interdisciplinary teams of neurosurgery and
      interventional radiology specialists should evaluate and treat such patients by
      using diagnostic and therapeutic angiography and, if necessary, surgery.

PMID- 16302623
TI  - Arrested hydrocephalus and the presyrinx state. Case report.
AB  - Hydrocephalus is known to be associated with syringomyelia; however, the
      association between arrested hydrocephalus and syringomyelia has been reported
      only once before. This presyrinx state is a recently recognized condition that is
      known to resolve with proper treatment. This case report highlights a rare
      association between arrested hydrocephalus and the presyrinx state and outlines
      the implications for treatment and etiopathogenesis. A 6-year-old girl with
      arrested hydrocephalus presented with a recent history of difficulty in walking
      despite no antecedent trauma or infection. An examination revealed macrocrania
      and features of cervical myelopathy, and magnetic resonance (MR) imaging revealed
      panventriculomegaly with evidence of the presyrinx state on both T1- and T2
      weighted images of the cervical spine. The patient underwent a procedure to
      insert a ventriculoperitoneal shunt that used a mediumpressure system. After the
      shunt was inserted, the patient's myelopathic symptoms gradually improved over a
      period of 6 months. Postoperative MR images obtained 1 year later revealed
      decompression of the ventricular system and complete resolution of the presyrinx
      state in the cervical spinal cord. Decompensation in arrested hydrocephalus is a
      well-known phenomenon. This case illustrates the concept that the presyrinx state
      may be one of the manifestations of decompensated arrested hydrocephalus. The
      importance of early recognition of this condition and its implications for the
      pathogenesis of syringomyelia are discussed.

PMID- 16302624
TI  - Anterior penetrating sacral injury in a child. Case illustration.

PMID- 16302625
TI  - Neonatal aneurysms.

PMID- 16302626
TI  - Cervical arthroplasty after previous surgery: results of treating 24 discs in 15
      patients.
AB  - OBJECT: The potential role of cervical arthroplasty in patients who have
      undergone previous cervical surgery is unknown. The authors performed a
      prospective study involving nonrandomized clinical and radiological assessment in
      patients who had undergone either previous posterior cervical foraminotomy or
      anterior interbody fusion and who suffered new or persistent arm/neck symptoms
      related to neural compression. METHODS: During a 30-month period, 15 patients who
      had previously undergone cervical spinal surgery underwent cervical arthroplasty
      that involved placement of the Bryan disc for neck or arm symptoms related to
      cervical disc disease. A total of 24 devices were implanted. Six of the 15
      patients had undergone a previous posterior foraminotomy, and in nine cases an
      anterior interbody fusion had been perfomed at some stage prior to surgery.
      Clinical and radiological evaluations were performed preoperatively and after
      surgery to assess outcomes. A total of 24 arthroplasties were performed
      encompassing between one and three levels. There were no major perioperative
      complications or immediate device-related failures. Two patients were lost to
      follow up. The follow-up period ranged from 12 to 43 months (mean 24.2 +/- 10.5
      months). Good results were obtained in all cases as reflected by an increase in
      the visual analog scale score of 6.4 in terms of neck/arm pain (p < 0.05). There
      was no difference in Oswestry Disability Index scores for neck pain (p > 0.05)
      and no patient required surgery at the same level. In one patient hypermobility
      developed with internal subluxation of the device, which suggested a compromise
      adjacent to a two-level fusion at 21 months. The segment was hypermobile
      preoperatively. The patient has experienced recurrent neck pain but otherwise
      remains clinically well and has not required revision surgery to date.
      CONCLUSIONS: Insertion of the Bryan artificial cervical disc in patients who have
      previously undergone cervical fusion or posterior foraminotomy, in general,
      appears to be safe. It provided encouraging early clinical results, although
      patients with preoperative hypermobility should be treated with caution. Issues
      such as accelerated device-related wear and the use of arthroplasty after
      aggressive facetectomy resection will need further study; however, in carefully
      selected patients who have undergone previous surgery cervical arthroplasty may
      provide an additional tool in the management of cervical disc disease.

PMID- 16302627
TI  - Magnetic resonance imaging evaluation of adjacent segments after disc
      arthroplasty.
AB  - OBJECT: Disc arthroplasty in the lumbar spine is an alternative to fusion when
      treating discogenic pain. Its theoretical benefits include preservation of the
      motion segment and the potential prevention of adjacent-segment degeneration.
      Despite the need to evaluate the benefit of preserving the adjacent segments
      after disc replacement, no study has been conducted to assess the ability of
      magnetic resonance (MR) imaging to depict the adjacent segments in patients who
      have undergone disc replacement surgery. METHODS: Postoperative lumbar MR images
      were obtained in the first 10 patients in whom a metal-on-metal disc arthroplasty
      system was used to treat the L4-5 or L5-S1 levels. At the superior adjacent
      level, the superior endplate and disc space were demonstrated on 90% of the
      images on both T1-weighted fluid-attenuated inversion-recovery (FLAIR) and T2
      weighted sequences despite the presence of artifacts. The inferior endplate at
      this level was documented on 70% of both T1-weighted FLAIR and T2-weighted
      sequences. At the level below the disc replacement in patients who underwent L4-5
      surgery, the superior endplate was demonstrated on 66.7% of the T1-weighted FLAIR
      sequences but only 33.3% of the T2-weighted images. The disc space and inferior
      endplate were depicted on 66.7% of both T1-weighted FLAIR and T2-weighted
      sequences. Axial images revealed an artifact in every adjacent space except at
      the L5-S1 level. CONCLUSIONS: Based on the results of this pilot study, it
      appears that sagittal MR imaging can be undertaken to evaluate the adjacent
      motion segment for degenerative changes following total disc arthroplasty in most
      patients. This imaging modality will provide an additional measure to assess the
      long-term efficacy of this intervention compared with other treatment modalities
      and the natural history of lumbar disc degeneration.

PMID- 16302628
TI  - Clinical and prognostic analysis of ossified ligamentum flavum in a Chinese
      population.
AB  - OBJECT: The authors performed a retrospective study of clinical and radiological
      data obtained in 27 Chinese patients with myelopathy induced by ossification of
      the ligamentum flavum (OLF) who underwent surgery between March 1990 and March
      2002. The factors related to surgical outcome of thoracic OLF-induced myelopathy
      were also assessed. METHODS: The preoperative clinical features and radiological
      findings were reviewed retrospectively. Preoperative and postoperative
      neurological status was assessed using the Japanese Orthopaedic Association (JOA)
      scoring system and the Nurick Scale. The ossified lesions were classified into
      five types (lateral, extended, enlarged, fused, and tuberous). Multiple linear
      regression and logistic regression analyses were performed to establish the
      factors affecting surgical outcome. The patients' chief complaints were lower
      limb weakness and gait disturbance (93%), numbness and sensory deficit (89%), and
      low-back pain (48%). The coexisting pathological entities were disc herniation,
      canal stenosis, and ossification of posterior longitudinal ligament. The ossified
      ligamentum flavum was mainly located at the T10-12 (67%) and T1-3 (15%) levels.
      Symptoms in 26 patients improved but resolved completely in only 14 after
      surgery. The mean overall JOA score was 5.3 +/- 1.9 preoperatively and 7.9 +/-
      2.3 postoperatively. There is a significant difference between the pre- and
      postoperative neurological status (p < 0.05) determined by the Student t-test.
      The recovery rate was 46.3 +/- 9.4%. Multiple regression analysis revealed
      negative correlation between the duration of preoperative symptoms and surgical
      outcome as well as a positive correlation between the preoperative JOA score and
      surgical outcome. Logistic regression analysis demonstrated that fecal and/or
      urinary incontinence, positive patellar and/or ankle clonus, and intramedullary
      high T2-weighted magnetic resonance (MR) imaging signal change had negative
      effects on the surgical outcome. CONCLUSIONS: The clinical and radiological
      features of OLF in the Chinese population are similar to those observed in the
      Japanese population. The duration of preoperative symptoms and JOA score are the
      most important predictors of the postoperative JOA score and recovery rate. The
      patients with fecal and/or urinary incontinence, positive patellar and/or ankle
      clonus, and intramedullary high T2-weighted MR imaging signal change were at
      higher risk of poor outcome after surgery.

PMID- 16302629
TI  - Surgical treatment of thoracic outlet syndrome: a randomized trial comparing two
      operations.
AB  - OBJECT: Various surgical approaches have been proposed for the treatment of
      thoracic outlet syndrome (TOS). The authors of this study focused on the
      differences in outcome after supraclavicular neuroplasty of brachial plexus (SNBP
      [no rib resection]) and transaxillary first rib resection (TFRR) in patients in
      whom the dominant clinical problem was pain. METHODS: Fifty-five patients were
      randomized to undergo TFRR or SNBP. Patients with an anomalous cervical rib,
      intrinsic weakness, and primarily vascular findings were excluded from the study.
      Preoperatively, the following findings were typically observed: provocation of
      symptoms by certain postures (the so-called spear-throwing position as well as
      downward tugging of the shoulder) and marked tenderness in the supraclavicular
      fossa. The intergroup severity of the symptoms was comparable. Eight patients
      were lost to follow up. There were 24 TFRRs (in two cases the procedure was
      bilateral) and 25 SNBPs. The mean follow-up interval was 37 months. In both
      groups pain decreased significantly after surgery. By all measures the TFRR
      operation conferred superior results. Patients reported significantly less pain
      (39 +/- 7 compared with 61 +/- 7; score range 0-100 on a visual analog scale),
      greater percentage of pain relief (52 +/- 8% compared with 30 +/- 7%), and less
      pain (3.7 +/- 0.4 compared with 5.1 +/- 0.5) on an affective scale (all p < 0.05)
      in the TFRR and SNBP groups, respectively). In the TFRR group, 75% of patients
      reported good or excellent outcomes compared with 48% in the SNBP group (p <
      0.05). CONCLUSIONS: Transaxillary first rib resection provided better relief of
      symptoms than SNBP. The major compressive element in patients with TOS-associated
      pain appeared to be the first rib.

PMID- 16302630
TI  - Effects of pilot hole preparation technique on pedicle screw fixation in
      different regions of the osteoporotic thoracic and lumbar spine.
AB  - OBJECT: The authors evaluated the effects of pilot hole preparation technique on
      insertional torque and axial pullout resistance in osteoporotic thoracic and
      lumbar vertebrae. METHODS: Using a probe technique and fluoroscopy, 102 pedicle
      screws were placed in 51 dual-energy x-ray absorptiometry-proven osteoporotic
      thoracic and lumbar levels. Screws were inserted using the same-size tapping, one
      size-under tapping, or no-tapping technique. Insertional torque and axial pullout
      resistance were measured. Analysis of variance, Fisher exact test, and regression
      analysis were performed. Same-size tapping decreased pullout resistance in the
      lumbar spine. There was no effect on pullout resistance in the thoracic spine.
      Pullout resistance values were lower for all insertion techniques in the upper
      thoracic spine. Insertional torque and bone mineral density correlated with
      pullout resistance in the thoracic and lumbar spine. CONCLUSIONS: Tapping
      decreased pedicle screw pullout resistance in the osteoporotic human lumbar
      spine, although it did not affect pullout strength in the thoracic spine. Tapping
      decreased insertional torque in upper thoracic levels. Surgeons should optimize
      overall construct rigidity when placing thoracic pedicle screws in patients with
      spinal segment osteoporosis.

PMID- 16302631
TI  - Quantitative anatomical and morphological classification of the iliac vessels
      anterior to the lumbosacral vertebrae.
AB  - OBJECT: Anterior surgical approaches to the lumbosacral disc spaces are being
      undertaken with increasing frequency. This increase and the use of minimally
      invasive techniques themselves have the potential to raise the incidence of major
      vessel injuries. The purpose of this study was to determine the variability of
      the vascular anatomy anterior to the lumbosacral spine and to draw conclusions
      regarding surgical accessibility of the L5-S1 disc space. METHODS: Thirty-five
      cadavers (age range at the time of death 31-87 years) were obtained to evaluate
      the anatomical features of iliac vessels with respect to the anterior approach to
      the lumbosacral spine. Direct measurement and morphological classification
      regarding the relations of these great vessels to the four arbitrary reference
      points of the lumbosacral disc space were performed. The mean width and height of
      the L5-S1 disc were 56.4 mm (range 41.6-65.4 mm) and 18.8 mm (range 10-24 mm),
      repectively. According to the authors' morphological classification, nine
      specimens (26%) were found to be Type A (standard), 12 (34%) Type B (narrow), two
      (6%) Type C (ajar), and 12 (34%) Type D (obstacle). CONCLUSIONS: The authors have
      noted quite a variation in the venous vascular anatomy anterior to the
      lumbosacral disc. During surgical planning for the anterior approach to the
      lumbosacral spine when using any technique, it is vital to assess carefully
      radiographic and neuroimaging studies to minimize potentially disastrous vascular
      complications.

PMID- 16302632
TI  - Superficial landmarks for the spinal accessory nerve within the posterior
      cervical triangle.
AB  - OBJECT: The spinal accessory nerve (SAN) within the posterior cervical triangle
      (PCT) is the most commonly iatrogenically injured nerve in the body.
      Nevertheless, there is a paucity of published information regarding superficial
      landmarks for the SAN in this region. Additional identifiable landmarks of this
      nerve may assist the surgeon in identifying it for repair, use of it in
      peripheral nerve neurotization, or avoiding it as in proximal brachial plexus
      repair. The present study was undertaken to provide reliable superficial
      landmarks for the identification of the SAN within the PCT. METHODS: The PCT was
      dissected in 30 cadaveric sides. Measurements were made between the SAN and
      surrounding landmarks. The mean distances between the entry site of the SAN into
      the trapezius and a midpoint of the clavicle, mastoid process, acromion process,
      and lateral aspect of the sternocleidomastoid (SCM) muscle were 6, 7, 5.5, and
      3.5 cm, respectively. The mean distances between the angle of the mandible and
      the mastoid process and the exit point of the SAN from the posterior border of
      the SCM muscle were 6 and 5 cm, respectively. The mean width and length of the
      SAN were 3 and 3.5 cm, respectively. CONCLUSIONS: It is the authors' hope that
      these data will aid those who may need to locate or avoid the SAN while
      undertaking surgery in the PCT and thus decrease morbidity that may follow
      manipulation of this region.

PMID- 16302633
TI  - Anatomical data on the craniocervical junction and their correlation with
      degenerative changes in 30 cadaveric specimens.
AB  - OBJECT: The goal of this project was to measure vertebral dimensions at the
      craniocervical junction and to investigate degenerative changes in this region
      and their correlations with the anatomical data. These studies will assist in an
      understanding of biomechanical conditions in this region, which are clinically
      relevant in cases of cervicogenic headaches and vertigo. METHODS: The authors
      examined 30 cadaveric specimens obtained from patients ranging in age from 24 to
      88 years at death. Measurements of angles of the vertebrae were conducted using
      an imprint method. Microsections of osseous endplates and articular cartilage
      were graded according to their degrees of degeneration by using the Petersson
      classification (0, no sign of degeneration; I, superficial degeneration with
      several fragmentations; II, deeper degeneration with cartilaginous disintegration
      and penetrating ulceration; or III, complete cartilaginous degeneration with the
      appearance of subchondral bone in > 50% of the articular surface). The authors
      found Grade I changes in 100% of the occiput specimens. In the superior articular
      cartilage of C-1 no changes (Grade 0) were found in two specimens, whereas 6% of
      the specimens exhibited Grade II changes and 89% exhibited Grade I changes. In
      the inferior articular cartilage of C-1, 57% of the specimens displayed Grade I
      changes, 14% Grade II, and 20% Grade III changes. In the superior articular
      cartilage of C-2, 62.5% of the specimens displayed Grade I changes and 25% Grade
      II changes. At the occiput-C1 level the authors found a higher frequency of
      degeneration at the upper left articular surface of the atlas (Quadrants 1 and
      3), and at the C1-2 level they found a higher frequency of degeneration at the
      upper left and upper right articular surfaces of the axis (Quadrants 2 and 3,
      respectively). Using the McNemar test, the authors investigated the frequency of
      affection of single quadrants in a left-right side comparison (lateral reversal).
      Significant differences were identified for Quadrant 2 of the upper left
      articular surface of C-2 and Quadrant 3 of the upper right articular surface of C
      2. These results correlate with the analysis of single articular surfaces of the
      axis, but contradict the results for the atlas, in which no significant
      difference in the left-right side comparison was found. CONCLUSIONS: Severe
      degeneration in the atlantooccipital joints appears to be a rare condition, with
      no Grade II or III degeneration found in the occipital condyles and 6% Grade I,
      89% Grade II, but no Grade III changes in the superior articular cartilage of the
      atlas. Degeneration of the inferior articular cartilage of C-1 and the superior
      articular cartilage of C-2 indicates that the atlantoaxial joint faces more
      intense mechanical exposure, which is increased at the upper joint surfaces.

PMID- 16302634
TI  - Dural arteriovenous fistula coexisting with a lumbar lipomeningocele. Case
      report.
AB  - The authors describe the case of a 44-year-old woman who presented with recent
      onset of progressive paraparesis and bladder involvement; she had an asymptomatic
      lumbosacral lipomatous swelling that was present since birth. Magnetic resonance
      imaging confirmed the diagnosis of a lipomeningocele. It also revealed
      intramedullary hyperintensity on T2-weighted images and serpiginous flow voids
      suggestive of a dural arteriovenous fistula (DAVF) at the same level; the lesion
      was confirmed by spinal angiography. Both lesions were surgically managed, and
      the patient subsequently experienced neurological improvement. The coexistence of
      a DAVF and a lipomeningocele at the same level is unusual and can lead to
      treatment failure if missed.

PMID- 16302635
TI  - Retrograde intraventricular hemorrhage caused by a traumatic sacral
      pseudomeningocele in the presence of spina bifida occulta. Case report.
AB  - The authors present the case of a large, posttraumatic sacral pseudomeningocele
      in the presence of spina bifida occulta. A pseudomeningocele in the sacral region
      is associated with trauma and with Marfan syndrome, but only one occurrence has
      been reported in association with spinal dysraphism. Trauma resulted in bleeding
      into the pseudomeningocele and retrograde passage of blood and fat into the
      ventricles. An oculomotor nerve palsy subsequently developed in the patient. The
      authors suspected a subarachnoid hemorrhage caused by a posterior communicating
      artery aneurysm, although this hypothesis was refuted on further investigation.
      The pseudomeningocele was drained by direct exposure of the neck and opening of
      the sac. Postoperatively, communicating hydrocephalus developed and the patient
      underwent ventriculoperitoneal shunt placement, resulting in resolution of the
      cranial nerve palsies. This first report of intradural bleeding from direct
      trauma to a pseudomeningocele illustrates the rare phenomenon of retrograde
      passage of blood from the sacral region to the brain. It also illustrates a
      possible but unlikely differential diagnosis of intraventricular blood and fat.

PMID- 16302636
TI  - Epithelioid hemangioendothelioma of the spine. Report of two cases.
AB  - Epithelioid hemangioendothelioma (EH) is a rare tumor of vascular origin. The
      authors describe two cases of spinal EH, one involving the T-10 vertebra and the
      second involving the upper cervical spine. In the first case the patient
      underwent resection of the tumor; this case represents the longest reported
      follow-up period for spinal EH. In the second case, extensive involvement of C-2,
      C-3, and C-4 as well as encasement of both vertebral arteries precluded safe
      tumor resection, and posterior occipitocervical stabilization was performed. The
      patient subsequently died of metastatic disease. The findings in these two cases
      underscore the difficulty in predicting the clinical behavior of spinal EH based
      solely on histological and clinical features as well as the uncertainty of the
      roles of surgery, chemotherapy, and radiotherapy in the oncological management of
      a spinal tumor for which clinical data are very limited.

PMID- 16302637
TI  - Split cord malformation with associated type IV spinal cord perimedullary
      arteriovenous fistula. Case report.
AB  - The authors describe the case of a 62-year-old woman with a Type II split cord
      malformation (SCM). At the initial time of workup, the authors observed an
      associated Klippel-Feil deformity at the level of the SCM and a low-lying conus
      medullaris; however, they discovered an associated Type IV perimedullary spinal
      cord arteriovenous fistula (AVF) only after the patient continued to deteriorate
      following a spinal cord untethering procedure. Although prominent blood vessels
      have been reported within the median cleft of SCMs, an angiographically and
      surgically proven perimedullary AVF has not previously been described. The
      potential coexistence of SCM and perimedullary AVF has significant clinical
      implications and its recognition is critically important prior to surgical
      treatment.

PMID- 16302638
TI  - Lumbar spinous process-splitting laminectomy for lumbar canal stenosis. Technical
      note.
AB  - In conventional laminectomy for lumbar canal stenosis (LCS), intraoperative
      damage of posterior supporting structures can lead to irreversible atrophy of
      paraspinal muscles. In 2001, the authors developed a new procedure for lumbar
      laminectomy, the lumbar spinous process-splitting laminectomy (LSPSL). In this
      new procedure, the spinous process is split longitudinally in the middle and then
      divided at its base from the posterior arch, leaving the bilateral paraspinal
      muscles attached to the lateral aspects. Ample working space for laminectomy is
      obtained by retracting the split spinous process laterally together with its
      attached paraspinal muscles. After successfully decompressing nerve tissues, each
      half of the split spinous process is reapproximated using a strong suture. Thus,
      the supra- and interspinous ligaments are preserved, as is the spinous process,
      and damage to the paraspinal muscles is minimal. Eighteen patients with LCS
      underwent surgery in which this new technique was used. Twenty patients in whom
      conventional laminectomy was undertaken were chosen as controls. At 2 years, the
      clinical outcomes (as determined using the Japanese Orthopaedic Association [JOA]
      scores and recovery rate) and the rate of measured magnetic resonance imaging
      documented paravertebral muscle atrophy were evaluated and compared between the
      two groups. The mean JOA score recovery rates were 67.6 and 59.2%, respectively,
      for patients treated with LSPSL and conventional laminectomy; the mean rates of
      paravertebral muscle atrophy were 5.3 and 23.9%, respectively (p = 0.0005).
      Preservation of posterior supporting structures and satisfactory recovery rate
      after 2 years indicated that this technique can be a useful alternative to
      conventional decompression surgery for lumbar canal stenosis.

PMID- 16302639
TI  - Translaminar rigid screw fixation of the axis. Technical note.
AB  - Rigid fixation of the axis with C1-2 transarticular screws or C-2 pedicle screws
      results in high fusion rates but remains technically demanding because of the
      risk of injury to the vertebral artery (VA) and the limitations imposed by
      anatomical variability. Translaminar fixation of the axis with crossing bilateral
      screws provides rigid fixation and is technically simple, is not affected by
      variations in individual anatomy, and does not place the VA at risk. The long
      term results in 20 patients treated with translaminar fixation for
      craniocervical, atlantoaxial, and axial-subaxial instability are presented, with
      100% fusion rates and no neurological or vascular complications. Translaminar
      screws may be a good option for rigid fixation of the axis for surgeons not
      proficient in the more technically demanding methods of stabilization.

PMID- 16302640
TI  - [Results of the study on antibiotic resistance emergence among pathogens of
      community-acquired urinary tract infections in Moscow. Phase I].
AB  - A rise of resistance in uropathogens to all agents used for the management of
      urinary tract infections has been observed in Moscow. However, because of the
      broad spectrum and favourable safety parameters, fluoroquinolones remain the
      drugs of choice for the treatment of community-acquired urinary tract infections.
      Among them levofloxacin is preferable. When the use of fluoroquinolones is
      contraindicated, the 1st-3rd generation cephalosporins are advisable. Nitrofurans
      are expedient in the treatment of acute and relapsing cystitis. By the
      antibacterial activity and bioavailability sodium furasidin is advantages among
      the nitrofurans.

PMID- 16302641
TI  - [Problems of prophylaxis and treatment of infectious complications in
      reconstructive surgery].
AB  - Infectious complications due to polyresistant staphylococci as well as strepto-
      and enterococci are of serious problem in reconstructive surgery, since the
      number of such strains isolated within 1999-2004 has amounted to 58.4-59.7% of
      all the isolates. Susceptibility testing of 195 isolates showed that 100% of them
      was susceptible to linezolid that was used in the postoperative treatment of 28
      patients after reconstructive surgical operations including those with artificial
      circulation under conditions of a multiprofile surgical hospital. Linezolid
      proved to be a highly effective agent in the prophylaxis and treatment of
      infectious complications due to polyresistant grampositive pathogens. Step-by
      step therapy with linezolid was shown possible. In the treatment of pediatric
      cases no side effects of linezolid were recorded.

PMID- 16302642
TI  - [Rational use of antibiotics in mucoviscidosis pediatric cases with an account of
      local microbiological monitoring].
AB  - The results of local microbiological monitoring of bronchial secretion in 482
      children with mucoviscidosis observed within 2000-2004 in the Republican Centre
      of Mucoviscidosis are presented. The results provided development of
      recommendations for rational use of antibiotics in the treatment of infectious
      processes in pediatric patients with mucoviscidosis. Since the emergence of MRSA
      in such patients is low, it is recommended to use antistaphylococcal betalactams
      (oxacillin, cefazolin, amoxycillin/clavulanate) for the treatment of infections
      due to S. aureus. For the treatment of infections due to some other pathogens,
      except S. maltophilia, the most active betalactams were carbapenems (imipenem and
      meropenem). Ciprofloxacin was active against numerous etiological agents causing
      low respiratory tract infections in children with mucoviscidosis except S.
      maltophila and A. xylosoxidans subsp. xylosoxidans. For the treatment of
      infections due to P. aeruginosa, P. aeruginosa muc. and K. pneumoniae the most
      active aminoglycosides were amikacin and tobramycin (for P. aeruginosa and P.
      aeruginosa muc.), while gentamicin was not active in such cases. As for
      antibiotics of other groups, high activity against S. aureus in the treatment of
      children with mucoviscidosis was recarded with the use of vancomycin, fusidic
      acid and rifampicin. Azithromycin and co-trimoxazole were active against H.
      influenzae. Chloramphenicol was active against S. maltophilia, B. cepacia and H.
      influenzae in the treatment of such patients.

PMID- 16302643
TI  - [Conference: validation. quality provision. Problems and solutions].

PMID- 16302644
TI  - Obesity, adipocytes and squirrels.

PMID- 16302645
TI  - Insulin resistance and cardiovascular disease: the role of PPARgamma activators
      beyond their anti-diabetic action.
AB  - Over the past few years it has been recognised that insulin resistance (IR) is an
      independent risk factor for major cardiovascular events. In addition, IR is
      associated with other factors such as hypertension, dyslipidaemia and endothelial
      dysfunction, and this cluster of metabolic disorders contributes to the
      cardiovascular risk of patients with IR. Given the increasing number of patients
      with IR, the modulation of their cardiovascular risk is a major task in
      diabetology and vascular medicine. This review will focus on the role of IR as a
      cardiovascular risk factor and on the potential of activators of the nuclear
      transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma)
      to modulate these risk factors associated with IR.

PMID- 16302646
TI  - Effects of low-dose continuous combined HRT on vascular function in women with
      type 2 diabetes.
AB  - BACKGROUND: Improvement in vascular endothelial function is widley cited as a
      beneficial effect of hormone replacement therapy (HRT). Women with type 2
      diabetes (T2DM) are at increased cardiovascular risk and have impaired
      endothelial function. Any benefits of HRT on endothelial function in this group
      are of particular interest. OBJECTIVES: We assessed effects on vascular function
      of oral 17beta oestradiol (1 mg) and norethisterone (0.5 mg) in postmenopausal
      women with T2DM. DESIGN: Double-blind, randomised, placebo-controlled trial.
      ASSESSMENTS: Twenty-eight women had pulse wave velocity (PWV) and adhesion
      molecules VCAM-1 and ICAM-1 assessed before and after three months' treatment.
      Twenty-four women also had gluteal fat biopsy for assessment of resistance vessel
      function (using wire myography). RESULTS: HRT did not affect PWV, VCAM-1, ICAM-1
      or carbachol response. Effects of L-NAME and indomethacin on carbachol
      sensitivity were similar in both groups. CONCLUSIONS: This HRT preparation had no
      detectable effect on these measures of endothelial function in women with T2DM.

PMID- 16302647
TI  - Enhanced left ventricular systolic function early in type 2 diabetic mice:
      clinical implications.
AB  - It is unclear whether the increase in availability of substrates for energy
      production in diabetes can lead to enhanced systolic function early in the
      disease, before the onset of structural changes to the myocardium. To examine
      this issue, BKS.Cg-m +/+ Lepr db (db/db) mice with type 2 diabetes and wild type
      controls had left ventricular pressure-volume relationships determined in situ.
      We demonstrated that the db/db mice, when compared to their wild type controls,
      generated greater left ventricular pressure and an enhancement of left
      ventricular systolic function based on enhanced power/EDV, positive dP/dt,
      preload recruitable stroke work, dP/dt--EDV relationship, and curvilinear end
      systolic elastance. This enhancement in systolic function occurred despite the
      db/db mice having greater body weight, but similar preload (end-diastolic volume)
      and afterload (effective arterial elastance). We postulate that the previously
      described enhancement in renal glomerular filtration rate seen early in type 2
      diabetes may be in part due to enhanced left ventricular systolic function early
      in this disease.

PMID- 16302648
TI  - [Multiple abdominal trauma: therapeutical options].
AB  - OBJECTIVE: To revise a series of multiple abdominal trauma in order to evaluate
      the type of diagnosis process and therapy undertaken, the complication and
      patient survival rates. PATIENTS: Three hundred ten patients of whom 294 (94.8%)
      with a single abdominal organ injury associated or not with trauma of extra
      abdominal organs (thorax, mediastinum, brain, bone) and 16 patients with a
      multiple abdominal injury (2 or more organs) associated or not with trauma of
      extra-abdominal organs. Age, gender, vital parameters, injury dynamics, number of
      organs, site of injury, Injury Severity Score (ISS), Abdominal Trauma Index (ATI)
      and Glasgow Coma Scale (GCS) have been recorded at admission. RESULTS: Multiple
      abdominal trauma represent 5% of all abdominal trauma. All trauma were closed
      ones: 14 street accident and 2 precipitations. A non operative management was
      undertaken in 6 patients, successfully completed in 2, while 4 patients required
      a surgical intervention to control bleeding within 12 hours of observation. Ten
      patients underwent immediate operation for unstable vital signs. The mean number
      of abdominal organs damaged was 2.8/patient. The mortality rate was 43.7% (7/16).
      All patients died during surgery. By comparing dead and surviving patient,
      initial haemodynamics and severity of ISS, GCS, and ATI scores were significant
      negative prognostic factors. The median length of hospitalisation of survivors
      was 12 days. CONCLUSIONS: Non operative management of multiple abdominal injury
      seems to be feasible in a small percentage and possibly only in selected cases.

PMID- 16302649
TI  - [Thyroid microcarcinoma in benign thyroid diseases].
AB  - INTRODUCTION: Thyroid microcarcinoma is a malignant thyroid tumor with potential
      multifocality and a maximum of 1 cm of diameter. This carcinoma has been
      discovered more frequently like incidentaloma. AIM OF THE STUDY: To appraise the
      incidence of MCT in the benign thyroid diseases and the advantages offered from
      the total thyroidectomy, performed for benign diffused thyroid diseases, which
      surgical treatment "therapeutic" performed for these malignant tumors. MATERIALS
      AND METHODS: The study was conducted on 600 patients operated with total
      thyroidectomy for benign thyroid disease, admitted from 1999 to 2003. RESULTS:
      All patients were alive and free of disease at last control. DISCUSSION: The MCT
      is a carcinoma that presents frequently a behavior little malignant and a good
      prognosis. His principal characteristic is the absence of clinical
      demonstrations. Therefore his discovery, almost always accidental on a thyroid
      removed for other pathology, it has signaled by histologic study CONCLUSIONS:
      Thyroid microcarcinoma is a slow growing tumor, with a good prognosis and with a
      good disease-free survival. It can present a better aggressiveness for his
      multifocal localization and invasion. Therefore total thyroidectomy can be
      considered best treatment and also be surgical treatment oncologically correct
      for this tumor.

PMID- 16302650
TI  - Laparoscopic adrenalectomy: transperitoneal lateral approach. Cases study.
AB  - AIM OF THE STUDY: To compare the results of the laparoscopic adrenalectomy
      achieved with the traditional laparotomic one. MATERIAL AND METHOD: In the period
      1997-September 2004 we treated 17 patients with adrenal pathology: eight patients
      underwent to an open anterior transperitoneal adrenalectomy and nine patients
      underwent a laparoscopic adrenalectomy with lateral transperitoneal approach.
      RESULTS: Among the immediate results a longer operative time was evident in the
      laparoscopic approach and a greater blood loss in the open approach; there were
      no conversions to a laparotomic procedure. In the postoperative period there were
      some bronchopneumonic infiltrates and some infections of the laparotomy in the
      open group; in the laparoscopic group there was a parietal haematomas that
      cleared up spontaneously, in correspondence of a trocar access. DISCUSSION: Both
      procedures allow to achieve the complete resolution of the adrenal pathology if
      it is confined within the gland and no more than 8 cm. in size. The morbidity in
      the mininvasive approach is surely much lower than the open technique. The
      advantages of a laparoscopic approach can be found in a minor surgical stress.
      The evident datum that results from the literature analysis of the results of the
      the laparoscopic adrenalectomies, is the very rapid resumption of the normal
      activities in the postoperative course. CONCLUSIONS: The laparoscopic
      adrenalectomy with lateral transperitoneal approach is a safe and efficacious
      procedure. Therefore, the AA can believe that the laparoscopic approach is at
      present the gold standard in the treatment of all benign adrenal pathologies with
      a no more than 8 cm. size.

PMID- 16302651
TI  - Surgical treatment and MRI in phyllodes tumors of the breast: our experience and
      review of the literature.
AB  - AIMS: To reassess the relationship between magnetic resonance imaging (MRI)
      findings and surgical resection margins in an attempt to address the issue of
      appropriate surgical management of phyllodes tumors (PT). METHODS: Three female
      patients with a large palpable mass suspicious for phyllodes tumors were studied
      by mammography (MX), ultrasound (US) and dynamic MRI and then underwent surgery.
      RESULTS: MRI demonstrated a rapidly and markedly enhancing multi-lobulated
      lesion. T1-weighted and T2-weighted sequences showed inhomogeneous signal
      intensity for the presence of cystic areas with internal septation and
      hemorrhage. Some areas of linear enhancement were present around the mass only in
      one case. Surgical management was mastectomy in one patient and wide excision in
      the other two patients. The margins in one of the latter patients were not clear,
      so mastectomy with immediate prosthetic reconstruction was subsequently
      performed. Pathological results showed 1 case of benign phylloides tumor, 1 case
      of borderline phylloides tumor and 1 case of malignant phylloides tumor.
      CONCLUSIONS: MRI enabled complete visualization of the tumor even in the region
      close to the chest wall, as well as clear delineation from healthy glandular
      tissue and may help to define the appropriate surgical management of phylloides
      tumor.

PMID- 16302652
TI  - [Follow-up of patients submitted to antireflux laparoscopic treatment. A study by
      a telephone questionnaire].
AB  - OBJECTIVE: As it is difficult to submit patients to instrumental follow-up after
      laparoscopic treatment of the gastroesophageal reflux disease (GERD), it is not
      easy to have a complete patients analysis after fundoplication. Telephone
      questionnaire can be a valid instrument to investigate clinical outcome and
      patients satisfaction to surgery. METHODS: This study discusses the results
      acquired through a telephone questionnaire which has been administered to
      patients undergoing laparoscopic fundoplication to study postoperative clinical
      evolution of GERD and satisfaction to surgery through a numerical rating scale
      from 1 to 10. RESULTS: Sixty three patients, who had a laparoscopic antireflux
      procedure at Department of General Surgery of the University of Udine (Italy),
      answered to telephone questionnaires. Fifty patients (74.9%) reported no
      symptoms. Patients satisfaction to surgery was 7.93 +/- 2.36. Fifty eight
      patients (92.1%) would have repeated the operation and 59 (93.6%) would have
      advised it to a friend suffering of GERD. A significant difference of patients
      satisfaction between preoperative typical and atypical symptoms has been found
      (8.43 +/- 2.04 vs. 6.95 +/- 2.71 p < 0.05). DISCUSSION AND CONCLUSION: Telephone
      questionnaire is comparable with face to face consultation, allowing to do a
      correct clinical follow-up, to exclude patients accusing pathological acid reflux
      after fundoplication; however preoperative symptoms are not so accurate as
      postoperative symptoms. Their presence giustifies a postoperative oesophageal pH
      metry.

PMID- 16302653
TI  - [Surgical treatment of liver hydatidosis: our experience with diagnostic and
      therapeutic consideration].
AB  - OBJECTIVE: The Authors report on their experience in diagnosis and treatment of
      liver hydatidosis (LH). MATERIALS AND METHODS: From January 2000 to December
      2003, we observed 24 patients (10 male = 42% and 14 female = 58%, male/female
      ratio 1:1.4, range of age 23 - 80 years, mean age 45.25 years). The most frequent
      initial symptom was hepigastric and hypocondriac pain (82.6%), meanwhile acute
      abdominal pain was only in 26.1%. In one half of cases performed radical surgery
      (total pericistectomy), in 35% of cases the AA subtotal pericistectomy and only
      in 17% the AA partial pericistectomy. Only one left hepatectomy during total
      pericistectomy we performed. Major complications were registered, except a post
      operative bleeding treated with 3 blood transfusion. The mean time of bedridden
      was 68 days (range 4 - 35, mode 7 days, median 7 days). All patients are actually
      in clinical, instrumental and serological follow-up as outpatients (3 months - 2
      years): we not encountered any relapse. CONCLUSIONS: The surgical treatment of
      liver hydatidosis must to be radical (as in total pericistectomy), free from
      severe and disabling complications and without risks and relapses. The choice of
      type of surgery (radical or conservative) must came from attempt examination of
      anatomo-clinical tools and experience and agreement of surgical team.

PMID- 16302655
TI  - [Nonoperative management of traumatic liver injuries].
AB  - BACKGROUND: Nonoperative management (TNO) of traumatic liver injury is the choice
      in hemodinamically stable patients without other abdominal injuries requiring
      celiotomy, apart from liver injury grading and amount of free peritoneal blood.
      CT-scan and angiographic embolization availability increase TNO feasibility.
      AIMS: To investigate feasibility of TNO in 16-months period consecutive liver
      injuries. MATERIALS AND METHODS: All data of severe trauma patients admitted to
      our facility during the study period were recorded. Clinical decision scheme of
      our facility indicates TNO in hemodynamically stable patients with liver injury
      and no need for celiotomy. CT-scan is performed and injury grading evaluated.
      Angiographic embolization is done if contrast medium extravasation is present at
      CT-scan. Laparoscopy is suggested if ongoing bleeding with negative CT-scan for
      blushing. RESULTS: Liver injury was detected in 34 of 452 severe trauma patients.
      Fifty percents of patients underwent TNO. In this group, bleeding control was
      achieved by angiographic embolization in 8 cases and by laparoscopy in 1. None of
      these patients needed celiotomy. None of TNO patients died. CONCLUSIONS: In a
      trauma referral center TNO of liver injury is possible in about 50%. TNO in
      severe trauma is improved if a correct CT-scan evaluation at the admission is
      performed and angiography correctly applied. Laparoscopy is an useful adjunctive
      tool in control of bleeding.

PMID- 16302654
TI  - [Typology of defunctioning colostomy and state of art in the treatment of bowel
      emergencies].
AB  - BACKGROUND: A trend toward avoidance of a defunctioning colostomy at emergency
      large-bowel surgery has been placed in recent years. The surgical management of
      patients with acute colonic disease has been evolving from multiple to single
      operations with a reduced use of colostomy. METHODS AND RESULTS: One hundred four
      consecutive non-selected patients underwent surgery for left-sided large bowel
      emergencies between 1980-2003. Defunctioning colostomy was performed in 10 out of
      58 resection-anastomosis procedures. Thirty-seven patients underwent Hartmann
      procedure, 9 received only diverting colostomy. Postoperative morbidity was
      28.8%. Postoperative mortality 8.2%. Anastomotic leak occurred in 1 and 6
      patients with and without defunctioning colostomy respectively. Four out of the 6
      patients without colostomy needed reintervention, while patient with covering
      colostomy underwent conservative treatment. Six (10.5%) out 56 patients with
      colostomy experienced major stoma related complications and underwent
      reintervention. DISCUSSION: Although there is general acceptance of one-stage
      surgery for right-sided colon emergencies, the surgical management of left-side
      large bowel obstruction and peritonitis remains controversal. Risk of anastomotic
      dehiscence associated with large-bowel anastomosis in unfavourable circumstance
      must be balanced against the high complications and low closure rates of a
      temporary colostomy. CONCLUSION: Primary resection and anastomosis without
      diverting colostomy for left-sided acute obstruction and peritonitis may be
      performed in selected patients. Diffuse purulent and faecal peritonitis are
      contraindications to one-stage surgery being necessary a two- stage procedure
      with loop or end colostomy. Colostomy remain a valid surgical option when high
      risk of dehiscence is suspected.

PMID- 16302656
TI  - [Extremity vascular traumas].
AB  - OBJECTIVE: The Authors report on a series of 61 vascular traumas treated over a 7
      years, separated in two groups. The first one includes 35 cases, that are street
      accidents, on the work and gunshot wounds. The second group includes 26
      iatrogenic causes due to arterial catheterism. METHODS: All patients underwent
      ecocolor Doppler directly in the operating theatre and, when this diagnostic
      procedure was not enough, pre-operating angiography was used (10 cases of complex
      traumas of the lower limb). RESULTS: One death was reported far each groups
      (3.27%). In 55 cases (90.1%), limb savage was achieved. In the others 4 (6.93%)
      of the first group, limb demolition was necessary for different causes. In the
      first group, severe neurological sequelaes were observed in 2 cases and motor
      deficits caused by tendon lesions in 1 case. CONCLUSION: The good results
      obtained are the result of the short ischemic interval between the acute event
      and treatment, thanks to a multidisciplinary approach of a specific equipe, that
      is rapid as possible.

PMID- 16302657
TI  - Iatrogenic splenic injuries.
AB  - Inadvertent intraoperative injuries to the spleen by the surgical team represent
      an underestimated complication of many abdominal procedures. Surgical reports
      often lack the necessary details and frequently a clear justification as why a
      splenectomy was indicated is not provided. The wide variability of the incidence
      reported in literature makes it is difficult to evaluate the morbidity and
      mortality associated to these injuries and to assess the early and late
      consequences of this complication, although it is still possible to infer some of
      the reasons for these inconsistencies and to roughly estimate both clinical and
      socio-economical effects of this injury. Given the degree of uncertainty on the
      incidence of iatrogenic and traumatic splenic injuries and on the immediate and
      long-term sequelae suffered by asplenic patients, we thought that a multicentric
      prospective study was warranted. We are therefore announcing the start of a study
      involving several Institutions within the Regione Campania, aimed at obtaining an
      unbiased estimate of the incidence of these injuries, together with the extent
      and severity of their long-term complications. We also aim to help promoting a
      more effective prevention.

PMID- 16302658
TI  - [Laparoscopic colorectal surgery: is the "learning curve" necessary?].
AB  - AIM OF THE STUDY: To present the early experience of the Authors' division in the
      field of colorectal laparoscopic surgery, in order to evaluate the so-called
      "learning curve". MATERIALS AND METHOD: From February 2003 to May 2004, we have
      performed 220 surgical procedures for colorectal pathology: 63 were conducted by
      a laparoscopic approach with 10 patients who, converted to a laparotomic
      procedure in theatre, were not taken under consideration. The present work is
      thus based on a population of 53 patients, 27 men and 26 women, at a median age
      of 64.4 y.o. (range 42-81). RESULTS: We performed 1 total colectomy, 24 right
      hemicolectomy, 1 resection of the splenic flexure, 12 left hemicolectomy (in 1
      case a left hepatic lobectomy was associated), 11 anterior resection of the
      rectum, 1 Hartmann' sigmoid resection and 3 abdomino-perineal resection. Mean
      operative time was 200.34 +/- 64.17 min, while the mean hospital stay was 6.44 +/
      2.68 days. Peri-operative mortality was 0%, 30-days mortality was 1/53 patients
      (9%) while morbidity was 5/53 patients (9.4%): in 2 cases reintervention was
      necessary. DISCUSSION: From the evaluation of the results, we found some
      significant data: first, the conversion rate was similar to those reported by
      other authors, so also the mortality and morbidity rates. CONCLUSIONS: The
      advantages of the laparoscopic technique, indirectly documented by shorter in
      hospital stay. At least for patients submitted to right or left hemicolectomy
      without complications (5.5 e 5.7 days, respectively), could be seen also after
      only a 1 year of activity. As far as the "learning curve" is concerned, dividing
      our activity into 3 times, we verified a progressive shortening of the operative
      time and, at least for the patients submitted to a right emicolecomy, also of the
      morbidity rates.

PMID- 16302659
TI  - Haemostasis and chemoprophylasis using a specific nasal packing after
      rhinosurgery.
AB  - AIM OF THE STUDY: This study evaluated the effect of a new type of haemostatic-
      chemoprophylactic nasal packing (gel-tampon) on wound healing following the
      surgical removal of nasal polyps. These tampons are coated with a haemostatic
      hydrocolloid gel supported by a latex of microfibres and were soaked in solution
      of cortisone and antimycotic or antibiotic medicament. MATERIAL AND METHODS:
      Seventy nine patients (56 M, 23 F, age 21-81, mean age 43 years) were studied
      following the above procedure. The gel-tampon was soaked in a solution of
      cortisone plus either antibiotic or antimycotic before postoperative application.
      A control group consisted of patients undergoing similar surgery and given nasal
      packing consisting of gel-tampon without having soaked them in any of the above
      solutions. The placement of the gel-tampon was easy and well tolerated by the
      patients. It was sufficient for haemostasis in all cases. Pain reported during
      removal of the gel-tampon soaked in solution was similar than in the controls.
      Subsequent haemorrhage in the study groups was both less frequent than in the
      controls, while the inflammation rate was considerable lower in the study groups
      in which was used antibiotic and cortisone. Soaking the gel-tampon in antibiotic
      + cortisone appeared to produce a better result than the use of antimycotic +
      cortisone. CONCLUSION: In conclusion it seems that the gel-tampon soaked in
      cortisone and antibiotic is a good possible solution for postoperative
      haemostatic and anti-inflammatory care following intranasal surgery.

PMID- 16302660
TI  - Neuromuscolar and vascular hamartoma of the duodenum. A clinical case and review
      of the literature.
AB  - BACKGROUND AND AIMS: The NMVH of the intestine is a rare lesion, typical located
      in the small bowel. After the first 2 cases, reported in 1982, other 12 cases
      have been described, ten localized in the jejunual or ileal tract, only 1 in the
      cecum. SUBJECTS AND METHODS: A case of NMVH of the duodenum, simulating a Crohns
      disease, is described. The lesion extended about 12 cm. and it caused intestinal
      stenosis. The microscopic analysis on the operative specimen highlighted the
      presence of a neuronal hyperplasia at mucous membranae and submucosal levels,
      associated to muscolaris mucosae hypertrophy and disorganisation. Expanded and
      ectasic veins, proliferation of nervous fibres and ganglion cells in the
      submucosal were also observed. RESULTS: NMVH is a non-epithelial hamartomatous,
      submucosally based proliferation of mature submucosal elements capable of causing
      small bowel obstruction. In the controversy about the nature of the NMVH, we
      consider it a separate entity, where the final diagnosis depend on the
      clinicopathologic setting, as well as on the location and number of the lesions.
      CONCLUSIONS: The Authors analyse the main characteristics of this rare pathology
      with regard to clinical, diagnostic and therapeutic aspects.

PMID- 16302661
TI  - [A rare complication of ERCP: Mallory-Weiss syndrome].
AB  - OBJECTIVE: To describe the management and outcome after endoscopic treatment of
      hematemesis by Mallory-Weiss Syndrome (MWS) occurred after CPRE (suspected
      choledocolithiasis). BACKGROUND DATA: Although cough and retching is common
      during EGD or CPRE, MWS resulting from endoscopy seems to be uncommon (0.0001
      0.04%) and always self-limiting. CASE REPORT: The patient was submitted to CPRE
      with the suspicion of choledocholithiasis. Eight hours after CPRE the patient
      presented with hematemesis and hypotension. With emergency EGD, the AA identified
      a small bleeding mucosal tear (visible vessel with spurting) just proximal to the
      esophagogastric junction. The patient was safely treated with endoscopic
      hemoclipping after the failure of sclerotherapy. CONCLUSIONS: The usefulness of
      hemoclipping in MWS is emphasized: although always self-limiting, endoscopic
      hemostasis is mandatory in high risk patients. The hemoclips are effective and
      safe in hemostasis in the case of bleeding visible vessel (spurting or oozing),
      even with or after sclerotherapy. The hemoclips not obstacles the healing.

PMID- 16302662
TI  - Gallstone ileus: report of a case successfully treated by a laparoscopically
      assisted enterolithotomy.
AB  - Gallstone ileus is an unusual cause of small bowel obstruction that occurs more
      frequently in elderly patients. The diagnosis is always very challenging and in
      most of cases this rare complication is misdiagnosed before surgery. The Authors
      report on a 81-year-old woman with small bowel obstruction who was
      laparoscopically diagnosed with gallstone ileus and successfully treated by a
      laparoscopically-assisted enterolithotomy.

PMID- 16302663
TI  - Bioethics consultation in the private sector.

PMID- 16302664
TI  - The ethics and aesthetics of for-profit bioethics consultation.

PMID- 16302665
TI  - Corporate ethics in the life sciences: can bioethics help? Should it?

PMID- 16302666
TI  - Bioethics consultation in the private sector: what is an appropriate model?

PMID- 16302667
TI  - Professional independence and corporate employment in bioethics.

PMID- 16302668
TI  - The epistemic explanation of government failure and the UK National Health
      Service.

PMID- 16302669
TI  - Promising, professional obligations, and the refusal to provide service.

PMID- 16302670
TI  - Professional promises and limits on the scope of practice.

PMID- 16302671
TI  - Protection of children and adolescents in psychiatric research: an unfinished
      business.

PMID- 16302672
TI  - Palliative care and its holistic model.

PMID- 16302673
TI  - Antiphospholipid antibodies and cell activation: crucial role of p38 MAPK
      pathway.

PMID- 16302674
TI  - Review: intravenous immunoglobulin therapy and thromboembolic complications.
AB  - Intravenous immunglobulin (IVIg) is used to treat a number of immune-deficiences
      and autoimmune diseases. Safety concerns related to a number of reported
      thromboembolic complications prompted us to review the literature. These
      complications happened mainly in individuals that had risk factors for
      thromboembolism, like advanced age, previous thromboembolic diseases, bed-ridden,
      and in individuals in which high doses or high infusion rates of IVIg were
      administered. The mechanism responsible for these events seems to be a rise in
      plasma viscosity that can trigger a thromboembolic event, especially in cases in
      which there is an underlying circulation impairment. Complications can be
      minimized by using IVIg only in clear-cut indications, weighting risk versus
      benefit in patients who are at high risk for thromboembolism and by sticking to
      carefully monitored slow infusion rates. IVIg for the treatment of autoimmune
      disorders should be administered as a five-day course of 2 g/kg of body weight.
      Each daily dose of 400 mg/kg should be given in not less than eight hours.

PMID- 16302676
TI  - Mast cells, TGF-beta1 and myofibroblasts expression in lupus nephritis outcome.
AB  - Renal biopsies of 69 patients with lupus nephritis were studied according to the
      WHO classification. The aim of the present study was to correlate the
      interstitial tryptase-positive mast cells with the interstitial TGF-beta1 and
      alpha-SM actin expression and clinical outcome of lupus nephritis, and identify
      the pathological role of the interstitial tryptase-positive mast cells in lupus
      nephritis. The mean follow-up time was 70.7 +/- 54.4 months. Eight patients were
      grouped as WHO class II lupus nephritis, 15 patients as class III, 28 patients as
      class IV and 18 patients as class V. Interstitial tryptase-positive mast cells
      were not correlated with clinical outcome and interstitial TGF-beta1 expression
      in lupus nephritis. Interstitial tryptase-positive mast cells were correlated
      with tubulo-interstitial alpha-SM actin expression for WHO class V lupus
      nephritis, but not to the other classes. In conclusion, in spite of interstitial
      tryptase-positive mast cells being related to renal interstitial fibrosis
      process, their expression according to the clinical outcome of lupus nephritis
      was not significant.

PMID- 16302675
TI  - Lymphocyte subpopulations and intima media thickness in primary antiphospholipd
      syndrome.
AB  - The aim of this study was to evaluate a possible association between lymphocyte
      subsets and intima media thickness (IMT) of carotid arteries in primary
      antiphospholipid syndrome (PAPS). We used a cross-sectional study on PAPS
      patients (n = 18) and healthy controls (n = 16). IgG anti-cardiolipin antibody
      (aCL), IgG anti-beta2glycoprotein-I (anti-beta2GPI), IgG anti-beta2glycoprotein-I
      complexed to oxidized low-density lipoprotein (oxLDL) and to a specific oxidized
      moiety of LDL (oxLig1), and beta2GPI-oxLDL were measured by ELISA. Lymphocyte
      immunophenotyping was performed using pairs of monoclonal antibodies directly
      labelled with fluorescein isothiocyanate, or phycoerythrin or phycoerythrin-Texas
      red-X. Intima media thickness (IMT) of carotid arteries was determined by high
      resolution sonography. Total peripheral blood lymphocytes did not differ between
      PAPS and controls. Memory CD4+/CD45RO + T cells were lower in PAPS than controls
      (P = 0.0007) as well as CD16+56+ natural killer cells (P = 0.02). In PAPS memory
      T CD45RO + cells positively correlated with IgG anti-beta2GPI-oxLigl (P = 0.002)
      and to IMT of carotid arteries (common carotid P = 0.02, bifurcation P = 0.007).
      Naive CD4+/CD45RA+ T cells inversely correlated with beta2GPI-oxLDL (P = 0.009).
      The relation between IgG anti-beta2GPI-oxLig1 and IMT of carotid arteries with
      memory CD45RO + T lymphocytes suggests a role for the latter in PAPS related
      atherogenesis.

PMID- 16302677
TI  - Serositis related to systemic lupus erythematosus: prevalence and outcome.
AB  - The objective of this study was to describe the prevalence and outcome of disease
      related serositis in Chinese patients with systemic lupus erythematosus (SLE).
      The records of all SLE patients who attended the medical clinics of Tuen Mun
      Hospital, Hong Kong were retrospectively reviewed. Patients with disease-related
      serositis at any stage of their illness were identified and the outcome of these
      serositis episodes was reported. Three-hundred and ten patients (90% women) who
      fulfilled at least four of the ACR criteria for SLE were studied. The mean age of
      SLE onset was 32.6 +/- 13.1 years. sixty-nine episodes of SLE-related serositis
      occurred in 37 patients - 18 (26%) episodes were pericarditis/ pericardial
      effusion, 30 (44%) were pleuritis/pleural effusion and 21 (30%) were
      peritonitis/ascites. The prevalence of serositis was 12%. At the time of
      serositis, 34 (92%) patients had active SLE in other systems. Nonsteroidal anti
      inflammatory drugs (NSAIDs) were initially used in 13 (35%) patients. Moderate to
      high doses of oral prednisolone was used in 28 (76%) patients for both serositis
      and concomitant disease activity in other organs. All episodes of serositis
      resolved completely within two months. Over a mean observation of 46 months, nine
      patients had 18 relapses of serositis, which were responsive to either NSAIDs or
      augmentation of prednisolone dosage. Pleural fibrosis developed in three
      patients. Serosal complications are not uncommon in patients with SLE and can be
      life-threatening. NSAIDs and corticosteroids are often effective but more
      aggressive immunosuppressive therapy is required for severe or refractory cases.
      The prognosis of lupus serositis is generally good. Relapse or progression to
      fibrotic disease is uncommon.

PMID- 16302678
TI  - Acute lupus myocarditis: clinical features and outcome of an oriental case
      series.
AB  - Symptomatic myocarditis in systemic lupus erythematosus (SLE) is uncommon. We
      describe the clinical characteristics, management and outcomes of 11 SLE patients
      without any atherosclerotic risk factors, who presented with acute lupus
      myocarditis (ALM). All patients were female, 46% Chinese with mean age of 27 +/-
      10 years at diagnosis of SLE. ALM was one of the initial manifestations of SLE in
      eight (73%) patients. The median duration from onset ALM to initiation of
      treatment was two weeks (range: 0.3-8). All had clinical feature of left
      ventricle dysfunction. The most common electrocardiographic feature was
      nonspecific ST/T wave changes (91%). Common echocardiographic findings included
      segmental wall motion abnormalities (81%) and decreased left ventricular ejection
      fraction (81%). Median SLE disease activity index at presentation was 16 (range:
      4-30). All patients received high dose corticosteroids and 64% received
      intravenous pulse cyclophosphamide. There were two deaths (18%) from infections.
      The remaining nine survivors had no recurrence of ALM nor suffer any SLE-related
      damage (median SLICC damage score of 0), up to a median follow-up of four years
      (range: 2.5-10.1). Repeat echocardiography after six months or later showed
      normal LVEF in eight patients (89%). Early immunosuppressive therapy in ALM, with
      high dose corticosteroids and pulse intravenous cyclophosphamide, results in good
      cardiac outcome.

PMID- 16302679
TI  - Clinical and serological features of 35 patients with anti-Ki autoantibodies.
AB  - The objective of this study was to analyse clinical and serological associations
      of anti-Ki antibodies. Thirty-five patients with anti-Ki antibodies, detected by
      CIE, selected from laboratory routine, were studied. All patients were affected
      by autoimmune diseases: SLE and pSS were the most frequent diagnoses. The cohort
      was constituted by 27 female and eight males. Main clinical features were skin
      involvement (60%), xerophtalmia (48.6%), Raynaud's phenomenon (43%),
      photosensitivity (34%), xerostomia (31.4%). CNS involvement was present in four
      (11.4%) and renal disease in seven cases (20%). ANA, anti-dsDNA and RF were
      detected in 100%, 60% and 34.5%. In SLE, anti-Ki was detected in 6% of cases,
      more frequently in males compared to other SLE patients without anti-Ki (P <
      0.004). Nineteen anti-Ki positive patients affected by SLE showed more frequently
      malar rash and multiple autoantibody specificities compared to 16 anti-Ki
      positive patients with other diseases (P = 0.044 and P = 0.0003, respectively).
      Our study confirms a preferential occurrence of anti-Ki antibodies in patients
      with sicca and skin involvement. Malar rash and multiple ANA specificities were
      significantly associated with SLE compared to other diseases in our study. Anti
      Ki were detected in 6% of patients with SLE with a significant prevalence in
      males.

PMID- 16302680
TI  - The functional p53 codon 72 polymorphism is associated with systemic lupus
      erythematosus.
AB  - The aim of the study is to investigate whether the functional p53 codon 72
      polymorphism is associated with susceptibility to SLE and its clinical features.
      A polymerase chain reaction of genomic DNA-restriction fragment length
      polymorphism was used to determine genotypes of the p53 codon 72 in 90 SLE
      patients and 114 healthy controls. Clinical/serological manifestations were
      analysed in each patient and correlated with the genotypes. The OR of the
      association of the Pro allele with SLE was 1.70 (95% CI, 1.15-2.53, P = 0.0079)
      and the OR of the Pro/Pro (a recessive model) was significantly increased (OR =
      2.58, 95% CI = 1.24-5.39, P = 0.0093). The Armitage's trend test indicated a
      significant dosage effect of the Pro allele for SLE (OR = 1.73, chi-square =
      7.08, P = 0.0078). However, there was no significant association of the
      polymorphism with clinical/serological manifestations studied here. In
      conclusion, our finding suggests the functional p53 codon 72 polymorphism may be
      associated with SLE susceptibility, suggesting individuals who carry the Pro
      allele may have a higher risk to SLE susceptibility than those with the Arg
      allele. Further studies for replications are needed to confirm that the p53
      polymorphism contributes to SLE.

PMID- 16302681
TI  - QT-interval parameters are increased in systemic lupus erythematosus patients.
AB  - Systemic lupus erythematosus (SLE) patients have increased cardiovascular
      morbidity and mortality. QT-interval parameters are presumed markers of
      cardiovascular risk and have not been previously evaluated in SLE. Standard 12
      lead ECGs were obtained from 140 female SLE outpatients and 37 age and body mass
      index-matched controls. QT interval was measured in each lead and heart rate
      corrected maximum QT-interval duration (QTcmax) and QT-interval dispersion (QTd)
      were calculated. Risk factors for cardiovascular disease and lupus clinical
      features, disease treatment, disease activity and damage index were recorded. SLE
      patients have increased QT-interval parameters when compared to controls (QTcmax:
      427.91 +/- 31.53 ms(1/2) versus 410.05 +/- 15.45 ms(1/2), P < 0.001; QTd: 52.38
      +/- 22.21 ms versus 37.12 +/- 12.88 ms, P < 0.001). These differences persisted
      after excluding those patients with arterial hypertension, diabetes and with ECG
      abnormalities (QTcmax: 419.90 +/- 28.78 ms(1/2) versus 409.15 +/- 15.85 ms(1/2),
      P = 0.041; QTd: 54.74 +/- 26.00 ms versus 37.96 +/- 13.05 ms, P = 0.001).
      Multivariate linear regression for factors associated with QTcmax selected the
      presence of electrocardiographic left ventricular hypertrophy (ECG-LVH) (P =
      0.003), nonspecific ST-T-wave abnormalities (P = 0.022) and left atrial
      enlargement (P = 0.044). Multivariate associates with QTd were age (P = 0.018),
      ECG-LVH (P = 0.022) and ST-T abnormalities (P = 0.031). In conclusion, SLE
      patients have increased QT interval parameters when compared to controls. This
      prolongation may lead to an increased cardiovascular risk. This finding might be
      due to subclinical atherosclerotic cardiovascular disease.

PMID- 16302682
TI  - Can systemic lupus erythematosus be the cause of collapsing glomerulopathy?
AB  - Collapsing glomerulopathy is a severe form of glomerular injury, closely
      associated with HIV infection, characterized by the collapsing feature of
      glomerular damage with frequent tubulointerstitial involvement and rapid
      progression to terminal renal failure. The etiopathogenesis in non-HIV infected
      patients remains obscure. We reported a patient whose diagnosis of collapsing
      glomerulopathy (CG) and systemic lupus erythematosus (SLE) was done
      simultaneously and described the diseases characteristics suggesting that SLE
      could be an etiologic factor for the induction of this glomerulopathy, clinical
      evolution and treatment.

PMID- 16302683
TI  - Mycophenolate mofetil for refractory haemolytic anemia in systemic lupus
      erythematosus.
AB  - Mycophenolate mofetil (MMF) has been increasingly used in patients with systemic
      lupus erythematosus (SLE). While most information concentrates on lupus
      nephritis, its efficacy in nonrenal manifestations of SLE has not been
      systematically studied. We describe the successful use of MMF in a patient with
      SLE-related hemolytic anemia that was refractory to cyclophosphamide, pulse
      methylprednisolone, intravenous immunoglobulin and cyclosporine. The mechanisms
      of action of MMF are briefly reviewed.

PMID- 16302684
TI  - Epidemiology of systemic lupus erythematosus in rural Wisconsin.
AB  - We investigated the epidemiology of systemic lupus erythematosus (SLE) in the
      Marshfield Epidemiologic Study Area (MESA), a defined rural region where nearly
      all residents obtain their health care from a large clinic system. Computerized
      medical records were searched to identify MESA residents diagnosed with SLE from
      1991 through 2001. Medical records were manually reviewed for all selected
      patients to identify cases of SLE using the 1982 revised American College of
      Rheumatology criteria. Patients with > or = 4 criteria were classified as
      definite SLE. Age- and gender-specific SLE incidence rates (1991-2001), the
      population prevalence rate of SLE on 31 December 2001 and survival rates were
      calculated. We identified 117 MESA residents with definite SLE. The average age
      adjusted incidence of definite SLE was 5.1 per 100 000 per year (95% CI: 3.6,
      6.6) and the age-adjusted population prevalence was 78.5 per 100 000 (95% CI:
      59.0, 98.0). The mean age at diagnosis among the 44 incident cases was 51.7 years
      (range: 14-90 years). Positive anti-nuclear antibody (ANA), hematologic
      abnormalities, arthritis and renal disease were common at diagnosis. Five- and 10
      year survival rates were 88% and 76%, respectively. Epidemiologic characteristics
      of SLE in this rural Caucasian population are generally similar to those reported
      by other US studies. One notable difference is a relatively high incidence of SLE
      in older adults.

PMID- 16302685
TI  - Ethnic disparities in health and disease: the need to account for ancestral
      admixture when estimating the genetic contribution to both (LUMINA XXVI).

PMID- 16302686
TI  - Avascular necrosis prevention with lipitor in lupus erythematosus.

PMID- 16302688
TI  - Membrane HSP70: the molecule triggering gammadelta T cells in the early stage of
      tumorigenesis.
AB  - Many studies support the supposition that HSPs expressed on the cell membrane
      play an important role in cancer immunity. In the present study, we demonstrated
      that HSP60 and HSP70 are markedly increased on the cell membrane of human Epstein
      Barr virus (EBV) transformed B cells. In order to investigate whether these
      molecules were involved in the response of human gammasigma T cells to
      transformed cells, the cytotoxicities of gammasigma T cells to transformed cells
      with or without an HSP60/70 gene knockdown were evaluated. gammasigma T cells
      showed marked cytotoxities to transformed cells. Down-regulation of HSP70
      expression could inhibit the reactions, whereas down-regulation of HSP60
      expression had little such effect. Moreover, HSP72 could significantly induce
      human gammasigma T cells to proliferate in vitro. Taken together, our data
      indicated that HSP60 and HSP70 could be valuable biomarkers for the prediction of
      early stage in tumorigenesis. Additionally, HSP72 might be a potential candidate
      of the adjuvant for gammasigma T cells in tumor immunotherapy.

PMID- 16302687
TI  - The production and characterization of novel heavy-chain antibodies against the
      tandem repeat region of MUC1 mucin.
AB  - Camelidae are known to produce immunoglobulins (Igs) devoid of light chains and
      constant heavy-chain domains (CH1). Antigen-specific fragments of these heavy
      chain IgGs (VHH) are of great interest in biotechnology applications. This paper
      describes the first example of successfully raised heavy-chain antibodies in
      Camelus dromedarius (single-humped camel) and Camelus bactrianus (two-humped
      camel) against a MUC1 related peptide that is found to be an important epitope
      expressed in cancerous tissue. Camels were immunized against a synthetic peptide
      corresponding to the tandem repeat region of MUC1 mucin and cancerous tissue
      preparation obtained from patients suffering from breast carcinoma. Three IgG
      subclasses with different binding properties to protein A and G were purified by
      affinity chromatography. Both conventional and heavy-chain IgG antibodies were
      produced in response to MUC1-related peptide. The elicited antibodies could react
      specifically with the tandem repeat region of MUC1 mucin in an enzyme linked
      immunosorbant assay (ELISA). Anti-peptide antibodies were purified after passing
      antiserum over two affinity chromatography columns. Using ELISA,
      immunocytochemistry and Western blotting, the interaction of purified antibodies
      with different antigens was evaluated. The antibodies were observed to be
      selectively bound to antigens namely: MUC1 peptide (tandem repeat region), human
      milk fat globule membrane (HMFG), deglycosylated human milk fat globule membrane
      (D-HMFG), homogenized cancerous breast tissue and a native MUC1 purified from
      ascitic fluid. Ka values of specific polyclonal antipeptide antibodies were
      estimated in C. dromedarius and C. bactrianus, as 7 x 10(10) M(-1) and 1.4 x
      10(10) M(-1) respectively.

PMID- 16302689
TI  - Introduction to 'picturing eggs, embryos and cells'.
AB  - Some twenty years ago, the historian of technology Henri Michel, who studied the
      history of instruments, wanted to draw our attention to the images des sciences
      (Michel 1977). Obviously, an instrument historian is well trained in dealing with
      pictorial matter, whether it may be blueprints of instruments, or detailed
      instructions about how to use and improve them. Further, instruments are
      extremely well suited media to demonstrate that theoretical knowledge has to be
      practically acquired, whether by making instruments, or by hand drawings. Also,
      historians of art have extensively worked, published and communicated on the
      issue of 'science and art' or 'science in art', and how their relationship shaped
      intellectual and technical history for several decades. As visualization denotes
      our ability to perceive, and to conceptualize, philosophy in general, and
      philosophy of science, in particular reflected about it and tried to grasp the
      scientists' epistemology. Over the last 25 years, an exceptional body of work was
      published on pictorial representation, either from a socio-cultural perspective,
      with an emphasis on the technology, or from the epistemic issue of how to
      conceptualize an eidon.

PMID- 16302690
TI  - Karl ernst von Baer's 'Uber Entwickelungsgeschichte der Thiere II' and its
      unpublished drawings.
AB  - In 1828 Karl Ernst von Baer (1792-1876) published his seminal Uber
      Entwickelungsgeschichte der Thiere. Beobachtung und Reflexion. In the preface he
      announced that a second volume with one copper plate would be finished 'in a few
      weeks'. However, it took nine years until the unfinished second volume was
      released, with four copperplates. In his 'Autobiography', von Baer did not
      clarify the reasons why he did not finish his research program of comparative
      embryology. The paper attempts to elucidate them, furnished by archival documents
      and von Baer's unpublished embryological drawings. Our sketch of a few figures
      will show that (1) von Baer searched for 'analogies' (homologies) as a unifying
      principle and (2) explained the mechanisms of embryogenesis by physiological
      reasoning (electromagnetism). The main objective is to show that technical
      problems in illustrating and conceptual difficulties impeded von Baer's ambitious
      research program.

PMID- 16302691
TI  - The history of the plant embryo. Terminology and visualization from ancient until
      modern times.
AB  - Since ancient times comparisons between embryonic forms of humans, animals, and
      plants are known. In deciphering a plant embryo and its development, one applied
      a specific zoomorphic terminology. Until the 17th century naturalists who studied
      plants were inspired by the concepts of ancient natural philosophy. Since then
      plant embryos are visualized by drawings and diagrammatic sketches. In the 18th
      century the embryo became an important issue in debates concerning theories of
      generation and the analogy between animal egg and vegetable seed was emphasized.
      Due to the cell theory and refined microscopic techniques around 1850 botanists
      described the 'plant embryo' as an aggregate of cells. The 20th century profited
      of further technical improvements, e.g. microphotography, SEM, and plant tissue
      culture. The spell of the word embryo integrated morphological and morphogenetic
      data in botany and served as a code to decipher botanic forms. The paper presents
      a short history of the concept of 'plant embryo' and focuses on its distinct
      meanings over centuries, supported by different images.

PMID- 16302692
TI  - The virtue of being too early: Paul A. Weiss and 'axonal transport'.
AB  - The essay introduces how Paul A. Weiss (1898-1989) analyzed his data on neuronal
      outgrowth and axonal transport, supported by constriction experiments of
      thousands of living mature nerve fibers. At the University of Chicago his group
      measured the steady proximo-distal flow of nerve fibers. To visualize the data he
      used tissue culturing, light microscopy, radioactive tracers, time-lapse motion
      pictures and electronmicroscopy. The work resulted in the discovery of
      fasciculation of outgrowing nerves and a computation of the rate of axonal
      transport, published in a classical article in 1948. He stated that the outgrowth
      of nerve fibers occurs from nerve centers in their nucleated cell bodies by
      fasciculation and protein synthesis. However, at that time one suspected the
      published microphotograph to be an idealized image and, therefore, did not accept
      the analysis, or the 'new' knowledge. In the mid 1960s the improved technique of
      autoradiography confirmed in an indirect way Weiss data and analysis of axonal
      transport. The objective here is to show (1) how Weiss employed the visibility of
      micrographs and drawings to corroborate his observations and analysis on axonal
      dynamics, and (2) to offer some tentative suggestions why his colleagues did not
      accept the 'neuro-images' as an evidence of new knowledge.

PMID- 16302693
TI  - From experimental imaging techniques to virtual embryology.
AB  - Modern embryology increasingly relies on descriptive and functional three
      dimensional (3D) and four dimensional (4D) analysis of physically, optically, or
      virtually sectioned specimens. To cope with the technical requirements, new
      methods for high detailed in vivo imaging, as well as the generation of high
      resolution digital volume data sets for the accurate visualisation of transgene
      activity and gene product presence, in the context of embryo morphology, were
      recently developed and are under construction. These methods profoundly change
      the scientific applicability, appearance and style of modern embryo
      representations. In this paper, we present an overview of the emerging techniques
      to create, visualise and administrate embryo representations (databases, digital
      data sets, 3-4D embryo reconstructions, models, etc.), and discuss the
      implications of these new methods on the work of modern embryologists, including,
      research, teaching, the selection of specific model organisms, and potential
      collaborators.

PMID- 16302694
TI  - 'Show me your original face before you were born': the convergence of public
      fetuses and sacred DNA.
AB  - Embryology is an intensely visual field, and it has provided the public with
      images of human embryos and fetuses. The responses to these images can be
      extremely powerful and personal, and the images (as well as our reactions to
      them) are conditioned by social and political agendas. The image of the
      'autonomous fetus' abstracts the fetus from the mother, the womb, and from all
      social contexts, thereby emphasizing 'individuality'. The image of 'sacred DNA'
      emphasizes DNA as the unmoved mover, the eidos, the soul of the human being.
      Since fertilization involves the forming of a new constellation of DNA in the
      zygote, the act of fertilization is being perceived as the secular and technical
      equivalent of ensoulment. This privileges fertilization above the other possible
      scientifically valued times when 'human life' begins.

PMID- 16302695
TI  - Selected works by Ivan Timofeevich Frolov (1929-1999) relative to the philosophy
      of homo sapiens et humanus.

PMID- 16302696
TI  - Milestone in the history of hematology.

PMID- 16302697
TI  - The value of the deoxyuridine suppression test in megaloblastic anaemia.

PMID- 16302698
TI  - Clinical effect of urokinase on chronic glomerulonephritis (group study).

PMID- 16302699
TI  - The action of some veratrum alkaloids on isolated frog nevre.

PMID- 16302700
TI  - Acute renal failure in a glucose-6-phosphate dehydrogenase deficient individual
      with infectious mononucleosis.

PMID- 16302701
TI  - Surface markers of lymphocytes and immunoglobulin alterations in chronic
      lymphocytic leukemia (CLL).

PMID- 16302702
TI  - Platelet aggregation and adhesiveness in severe iron deficiency due to
      menorrhage.

PMID- 16302703
TI  - [Use and mechanism of botulinum toxin in overactive bladder treatment].
AB  - Overactive bladder is very frequent in central neurogenic patients; it is a major
      cause of refractory incontinence despite anticholinergic treatment. In non
      neurogenic patients it results in very distressing symptoms that associate
      urgency with or without incontinence and frequency. Botulinum toxin A is a well
      known agent used previously in the treatment of striated muscle spasmodism, which
      blocks the release of acetylcholine from nerve endings and neuro-muscular
      transmission. Its recent use in urology revealed a dramatic improvement in
      clinical and urodynamic parameters of the overactive bladder, associated with a
      long lasting effect over 6 to 9 months and an excellent tolerance. In neurogenic
      patients, the efficacy of botulinum injection was demonstrated over a placebo
      control group. Toxin was injected at 20 to 30 different sites in the detrusor
      muscle, with cystoscopy guidance. Recent studies showed a sub-epithelial
      mechanism of action on neuropeptides, which could explain an inhibitory effect of
      both efferent and afferent arms of the micturition reflex. Further studies remain
      necessary regarding the respective doses of Dysport and Botox toxin, selection of
      patients, combination with anticholinergic treatment, effects of repeated
      injections.

PMID- 16302704
TI  - [Intermittent hormone therapy for prostate cancer].
AB  - Intermittent hormone therapy in prostate cancer consists in disrupting treatment
      after the nadir PSA has been reached, and reinitiating treatment when the PSA
      increases over a certain threshold. Theoretical advantages of intermittent
      hormone therapy are to delay the occurrence of hormone-independence and to
      decrease treatment-related side effects. Some phase II trials have demonstrated
      the feasibility of intermittent hormone therapy. The percent time without
      treatment varies between 40 and 50%. Oncologic results of intermittent hormone
      therapy are, at least, equivalent to those of continuous therapy. Moreover, the
      side effects of treatment are decreased and the quality of life is improved
      during off treatment phases. Due to the lack of comparative studies, the
      superiority of intermittent upon continuous treatment has not been established at
      long-term follow-up. Prospective comparative trials are ongoing; they will
      determine the true benefit of intermittent hormone therapy in prostate cancer.

PMID- 16302705
TI  - [Suburethral bands in women urinary stress incontinence: a review of the various
      techniques].
AB  - With more than 1,000,000 procedures in the world and the good results that have
      been published (85% recovery rate, low morbidity), Tension free Vaginal Tape
      (TVT) is now considered the gold standard for the treatment of female urinary
      stress incontinence. Currently, advances are noticed concerning the material used
      (monofilament, multifilament or extruded cross-linked polypropylene), the
      surgical access (ascending or descending retropubic, transobturator approach),
      and the ancillary instruments. The surgeon's vigilance is essential in selecting
      the most adapted material and access to obtain good results and the lower
      morbidity rate.

PMID- 16302706
TI  - [Extra corporeal shock wave lithotripsy (ESWL) procedure in urology].
AB  - Since 1980, extra corporeal shock wave lithotripsy (ESWL) has become the first
      line treatment for most stones in adults and children. The indications are based
      on criteria depending on localization, chemical composition and size of the renal
      and ureteral calculi. Since the DORNIER HM 3 which remains the gold standard of
      first generation lithotripters, many devices of second and third generation have
      been built (electro hydrolic, piezo electric and electromagnetic) with
      fluoroscopic and ultrasound localization systems. SWL may now be performed on an
      out-patient basis without anaesthesia or under neuroleptic analgesia. Indications
      and evaluation criteria on 3 months plain abdominal X-ray are better defined
      since 1996. Nevertheless, comparison of reported results remains difficult due to
      the multiplicity of lithotripter types and the lack of consensus on efficacy
      criteria. Today, the third generation of mobile electromagnetic lithotripters
      give an average of 80% stone free rate of patients with kidney and ureteral
      calculi whatever the localization and size.

PMID- 16302707
TI  - [Tribute to Andrew V. Schally].

PMID- 16302708
TI  - [Recent data on GnRH receptors].
AB  - The main intracellular pathway activated by stimulation of GnRH receptors is
      related to Gq protein which induces a cytoplasmic metabolic cascade responsible
      for activation of genes producing gonadotrophins and regulating their secretion.
      Two other activation pathways were identified, a Gs protein-mediated pathway
      involved in pulsatile secretion of GnRH and a Gi protein-mediated pathway with an
      inhibitory and apototic effect on tumor cells. Finally, GnRH receptors may
      directly interact with membrane integrins and generate other cytoplasmic signals.
      Hence, GnRH receptors are not only involved in pituitary secretion but also in
      tumoral disease. The inhibitory effect of GnRH analogs on the secretion of sex
      steroids is responsible for the indirect anti-tumoral action already used in
      routine practice for the treatment of hormone-dependent cancer. However, the
      presence of GnRH receptors in tumor tissues suggests that they are directly
      involved in cancerous disease. The conformational variability of these receptors
      permits certain ligands to stabilize them in a form privileging various
      intracellular signals with activation of metabolic pathways involving protein
      kinase systems and generating a direct antitumoral effect by inhibition of cell
      growth and?or apotosis. The absence of an intracytoplasmic C-terminal tail in the
      structure of these receptors is an essential condition for the anti-proliferative
      effect of various ligands, agonists or antagonists, with an anti-tumoral activity
      varying according to their specificity. This will make it possible in the future
      to establish a new classification of GnRH analogs. The discovery of this direct
      antitumoral effect has therefore opened up a new therapeutic approach for hormone
      independant cancers with GnRH receptors and the direct cytotoxic effect
      reinforces the hormonal action in hormone-dependant cancers.

PMID- 16302709
TI  - [GnRH resistance and the GPR54 gene].
AB  - Current data make it possible to relate idiopathic hypogonadotrophic hypogonadism
      to mutations affecting the GnRH I-1 receptor and also to new "loss-of-function"
      mutations concerning another receptor, GPR54. It now seems that mutations of the
      pituitary GnRH receptor are not the only explanation of most cases of sporadic
      isolated hypogonadotrophic hypogonadism, and, on the contrary, there are certain
      familial forms, where no mutation has been demonstrated, suggesting the potential
      involvement of other genes. The role of another G protein-coupled glycoprotein
      membrane receptor, GRP54, already known for its involvement as a metastasis
      suppressor, has been demonstrated. Bioclinical studies of families affected with
      the disorder by pheno/genotypic correlation demonstrated that "loss-of-function"
      mutations affecting the GPR54 gene coding for GRP54 are the cause of
      hypogonadotrophic hypogonadism. GPR54 therefore appears to be involved at
      hypothalamic and pituitary level. It is not involved in sexual differentiation,
      but may modulate GnRH secretion or affect its pituitary response. Further
      investigations are required to determine the levels of action of this receptor
      which may provide a new pharmacological target in the future.

PMID- 16302710
TI  - [The discovery of hypothalamic hormones and the development of antitumor
      analogs].
AB  - Although after the discovery of GnRH, research was initially directed towards the
      treatment of infertility, the development during the last twenty-five years of
      synthetic GnRH analogs has led to major advances in the diagnosis and treatment
      of endocrine disorders and cancer. Agonists are 50-100 times more potent than the
      natural neuropeptide and induce an intense and constant secretion of
      gonadotrophins, while their continuous administration induces hypophyseal
      desensitization with a fall in FSH and LH production leading to a reduction in
      sex hormones production and therefore chemical castration. This has been used for
      the treatment of precocious puberty, in vitro fertilization protocols and
      management of various hormone-dependent cancers such as prostate and breast
      cancer, a field where these indications are being continually extended. LHRH
      antagonists, used at doses higher than those of agonists, induce an immediate
      inhibition of gonadotrophin secretion and rapidly reduce sex steroid levels.
      Their development is more recent, and they have begun to find a role in prostatic
      diseases, cancer and benign prostatic hypertrophy. The discovery of GnRH
      receptors in various types of cancer has suggested a direct cytotoxic effect on
      cancer cells as well as the indirect hormonal effect. Research currently in the
      preclinical stage involves the use of combinations of ligand analogs and
      cytotoxic agents to increase the anti-tumoral specificity of chemotherapy and
      provide greater efficacy and reduced collateral toxicity. The management strategy
      of prostate, breast and ovarian cancers may therefore be considerably modified.
      Likewise, this concept of targeted chemotherapy using analogs acting as cytotoxic
      agent carriers up to the tumor site is the aim of research to evaluate
      somatostatin and bombesin.

PMID- 16302712
TI  - [GnRH antagonists: present and future].
AB  - Antagonists act by competitive inhibition of pituitary GnRH receptors for which
      they have a high affinity with a dose-dependent activity. The inhibition concerns
      LH but also FSH by inhibiting their secretion for 24 hours. At this time, only
      three molecules are available. Cetrorelix is mainly used for in vitro
      fertilization protocols, but research is currently being carried out in benign
      prostatic hypertrophy. Ganirelix is only used in medically assisted procreation.
      Abarelix is used in the United States as a monthly "depot" injection for the
      treatment of prostate cancer resistant to other therapies. Other molecules
      including orally active antagonists are in the course of clinical evaluation or
      in preclinical phases. The development of this therapeutic class is hampered by
      conflicting industrial interests and also by problems of tolerability in
      particular because of the side effects due to induced histamine release. The
      current indications in France are therefore limited to Assisted Reproductive
      Technology, and, recently, prostate cancer pending comparative studies versus
      agonists. The indications under development are endometriosis, myoma and
      precocious puberty, fields in which agonists have already been found to be
      effective. Male contraception seems to have a future however this therapeutic
      regimen remains very expensive. Finally, in benign prostatic hypertrophy, the
      antagonists administrated intermittently may be used to rapidly improve urinary
      flow.

PMID- 16302711
TI  - [GnRH agonists versus antagonists during in vitro fertilization].
AB  - During in vitro fertilization (IVF) GnRH antagonists or agonists are used to
      optimize the control of organization of oocyte collection. The choice of
      stimulation protocol also takes into account the ovulatory, clinical, biological
      and ultrasound characteristics of the FIV candidate, as well as any stimulation
      measures already taken. Age appears to be the major predictive factor of oocyte
      response to stimulation and ultrasonography on the 3rd day is a predictive
      element of the success of oocyte collection. Determination of hormonal parameters
      on the 3rd day of the cycle (FSH, oestradiol, inhibin B, anti-mullerian hormone)
      makes it possible to refine the choice of therapy. All these elements are used to
      define various categories of patients in terms of response to hormonal
      stimulation. Agonists induce a suppression of pituitary secretion which inhibits
      the preovulatory LH peak and blocks natural ovulation. Nevertheless, there is an
      initial transient stimulating effect (flare-up) for a few days and a risk of
      prolonged ovarian desensitization responsible for side effects. The antagonists,
      administered just before the supposed ovulatory phase, provoke a rapid diminution
      in LH while avoiding the flare-up and prolonged ovarian desensitization. Various
      meta-analyses to compare both types of treatments currently suggest that agonists
      are superior in terms of number of oocytes produced, though the percentage of
      mature oocytes obtained as well as the levels of fertility are comparable
      whatever the type of treatment. In practice, organization of stimulation
      protocols using agonists is easier especially for teams working in a sequential
      manner. However, protocols using antagonists may be particularly useful in poor
      responders and are globally better tolerated.

PMID- 16302713
TI  - [GnRH agonists and breast pathology].
AB  - The discovery of hormone receptors and tamoxifen has revolutionized the
      management of breast cancer in women as the existence of oestrogen receptors has
      improved the response rate to hormone treatment from 30 to 50-70% with a further
      increase in this efficacy if there are also progesterone-positive receptors. LH
      RH analogs induce medical castration. Their efficacy in combination with
      tamoxifen was demonstrated in terms of survival in pre-menopausal women with
      metastatic cancer. In the adjuvant situation, a meta-analysis of the 1980s
      demonstrated a benefit in terms of survival without relapse confirmed by more
      recent studies showing a reduction in the relative risk of relapse. On
      radiotherapy or ovariectomy, which are radical treatments, medical castration
      with LH-RH agonist analogs in combination with tamoxifen is therefore an
      alternative, reversible therapy for outpatients in particular now that a possible
      direct anti-tumor effect has been suggested by in vitro studies. Nevertheless, at
      present in France, Marketing Authorisation has not yet been granted for
      metastatic cancer.

PMID- 16302714
TI  - [GnRH analogs and prostate cancer treatment].
AB  - Prostate cancer is currently the main indication of LH-RH analogs. This class,
      which in recent years has replaced diethylstilbestrol and surgical castration,
      now plays a major role at all stages of the disease. Numerous studies with
      contradictory results have compared total hormonal blockage, an alog combined
      with an anti-androgen, with analog alone in locally advanced prostate cancer. A
      recent metaanalysis showed a slight though globally non-significant advantage in
      favour of total blockage, but with a significant advantage in the case of a
      nonsteroidal anti-androgen. In stage T3 cancers, adjuvant hormone therapy over
      three years in combination with radiotherapy versus external radiotherapy alone
      was more effective in terms of local or metastatic progression and survival.
      Institution during radiotherapy and a prolonged duration of treatment gives a
      greater benefit though this was only significant for the subgroup of patients
      with a Gleason score > or = 8. For localized stages but at high risk (PSA > 15 ng
      / ml and?or Gleason score > 7), adjuvant hormone therapy after prostatectomy
      improved recurrence-free survival in comparison with prostatectomy followed-up by
      simple monitoring. On the other hand, the administration of analogs two or three
      months before radical prostatectomy did not seem to provide any additional
      benefit. Medical castration prolonged by LH-RH analogs engenders multiple side
      effects which become all the more worrying as patient survival is prolonged by
      this hormone therapy. In phase I-II studies, intermittent treatment is equivalent
      to continuous treatment for "hormone sensitive" patients (PSA nadir at six months
      < 0.5 ng). Phase III studies are in progress to confirm this equivalence. This
      intermittent hormone therapy may be a useful solution for elderly patients (> 78
      years old) with a biologically highly active cancer and remains to be evaluated
      in relatively young subjects after radical prostatectomy or radiotherapy.
      Combination of analogs with chemotherapy has been used very recently for patients
      who have reached hormonal escape and may be a useful immediate option for
      patients with cancers with a high risk of progression.

PMID- 16302715
TI  - [GnRH antagonists and benign prostatic hyperplasia].
AB  - Early treatment of benign prostatic hyperplasia (BPH) helps to decrease the need
      for surgery and thus places the medical treatment at the forefront which implies,
      optimising its efficacy and tolerance. Alpha-blockers and 5-alpha-reductase
      inhibitors are the two main classes of currently used drugs. The role in the
      growth of glandular, muscular and fibroblastic tissues of the prostate of
      androgens, testosterone and especially intraprostatic dihydrotestosterone was
      properly established. These physiopathological data prompted to evaluate the
      efficacy of inhibition of the hypothalamic-pituitary-gonadal axis, by means of LH
      RH analogues. The agonists lead to a biological castration associated with a
      significant improvement of BPH symptoms. Unfortunately clinical relapse is
      systematic when treatment is discontinued. The antagonists, particulary
      cetrorelix, improve BPH symptoms, with a persistant benefit after treatment,
      discontinuation, although the effect on the prostate volume reduction is
      transitory. It can be suggested that beside the well known hormonal action, there
      is a direct apoptic effect cells as well as inhibition of the intratissue growth
      factors. The LH-RH antagonists could thus become an alternative to the current
      drugs by offering a relatively short treatment with a prolonged benefit.

PMID- 16302716
TI  - [Pharmacokinetics and pharmacodynamics of triptorelin].
AB  - GnRH agonists are derived from the native molecule by substitution of a D-amino
      acid in position 6 which increases their resistance to enzymatic breakdown and
      their affinity for LH-RH receptors in comparison with the native hormone. Because
      of this improved resistance which increases their half-life they have a super
      agonistic effect. In 1973, two years only after he characterized LH-RH, A.V.
      Schally synthesized several GnRH analogs, including D-TRP6-LHRH obtained by
      substituting the glycine-6 with a D-tryptophan. The biological half life of this
      agonist injected by the subcutaneous route is 10 times greater than that observed
      after intravenous injection because of the progressive release of the peptide
      from the injection site. Pharmaceutical research has led to the development of
      delayed-release formulations allowing doses to be spaced by intervals of several
      weeks, or even three months when needed in some indications (Decapeptyl slow
      release). Triptorelin, as the other GnRH agonists, strongly reduces LH secretion,
      by preventing the production of the LH-beta subunit. On the opposite, the
      production of LH-alpha subunit is markedly increased and remains responsive to
      exogenous GnRH injection, demonstrating that the agonist does not induce actual
      pituitary desensitization. Compared with LH-RH antagonists which inhibit both LH
      alpha and LH-beta subunit secretion, agonists offer the advantage of a sustained
      efficacy even after one or two days of withdrawal, while the effect of the
      agonist disappeared as soon as the administration is stopped. On the other hand,
      GnRH antagonists do not induce the initial hyperstimulation of the gonadotrophs,
      the so-called flare up, characteristic of the superagonistic effect.

PMID- 16302717
TI  - [Treatment of precocious puberty by GnRH agonists].
AB  - The objective of GnRH agonist treatment in precocious puberty is to block
      pubertal development, and to reduce the action of sex steroids on bone maturation
      in order to restore normal long-term growth of the skeleton. Currently available
      studies show a positive benefit-risk ratio of GnRH analogs in the treatment of
      precocious puberty. Adult heights obtained are in average greater than those
      predicted in the absence of treatment and close to the normal target height. The
      side effects observed during treatment such as headaches, asthenia or hot
      flushes, are related to sex steroid deprivation and are observed in 20 to 30% of
      cases. Questions remain concerning the impact of these treatments on intellectual
      development and body composition. Finally, to assess the impact on fertility,
      IPSEN laboratories decided to organize a prospective study on patients treated in
      the 1980-1990s. In pediatrics, a reduction in the number of injections is an
      important objective to improve compliance. "Depot" formulations with prolonged
      release over three months, already used in adult indications, represent a useful
      progress in pediatrics and have recently been assessed. The efficacy and safety
      of triptorelin acetate (Decapeptyl) administered at a dose of 11.25 mg every
      trimester for one year were evaluated in a European multicentre open trial
      including 54 girls and 10 boys. The LH peak during the GnRH test at three months
      was used as primary end-point. This slow release triptorelin was shown to be
      effective, similarly to delayed-acting leuprorelin. The auxological effects, in
      particular on adult height, were not evaluated in this study.

PMID- 16302718
TI  - Governor "takes under advisement" nurses' objections to his proposed
      reorganization.

PMID- 16302719
TI  - Comm. Bicknell attacks nurses' stand on H6120, accuses RN's of "arrogant
      irresponsibility".

PMID- 16302720
TI  - H 6120 vis-a-vis the public interest.

PMID- 16302721
TI  - "Achieve the Fix in '06" KMA launches campaign for liability reform.

PMID- 16302723
TI  - Dementia with Lewy bodies: a commonly unrecognized cause of dementia.
AB  - Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause
      of dementia of the elderly following Alzheimer's disease. The significant
      clinical features include: fluctuating cognition with pronounced variations in
      attention and alertness, recurrent visual hallucinations, and spontaneous motor
      features of parkinsonism. As an alpha-synucleinopathy, DLB is characterized by
      Lewy bodies of both classical and cortical types with neuritic degeneration. This
      report describes an autopsy of an elderly woman with DLB and reviews the clinical
      and pathologic features of dementia with Lewy bodies.

PMID- 16302722
TI  - Lethal envenomation: medicolegal aspects of snakebites and religious snake
      handlers in Kentucky: a report of three cases with comment on medical, legal, and
      public policy ramifications.
AB  - Ritualistic serpent qua snake handling, which rests upon inveterate religious
      conviction arising out of literal interpretation of selected passages of the New
      Testament, is a rare ceremony practiced by a distinct minority of Christians
      predominantly in rural Appalachian regions of the United States commonly referred
      to as the Bible belt. The fervent, frenzied pursuit by anointed "sign-followers"
      of intimate contact with a variety of poisonous snakes, however, puts the handler
      together with sect members or bystanders at risk for lethal envenomation,
      particularly when prompt medical attention is held by the congregation of faith
      to contravene God's will. The authors report three separate cases of death due to
      envenomation by snakebite during a church service and the handler's faith-based
      refusal to seek treatment. Postmortem examination of each yielded similar
      physical findings attributable to various toxic sequelae of the complex venoms. A
      review of the injurious constituents of these chemical toxins also includes a
      discussion of complex pathophysiological mechanisms causing death. In addition,
      the authors review the history of representative legislative and judicial
      responses to the sensationally mortal phenomenon, all of which ineluctably
      grapple with fundamental Constitutional issues devolving from such controversial
      religious practices. We underscore the view that a thoroughly documented
      medicolegal investigation and autopsy are indispensable to both inform matters of
      public health and thereby contribute to the formulation of sound public policy.

PMID- 16302724
TI  - Commitment.

PMID- 16302725
TI  - Osteoporosis.

PMID- 16302726
TI  - Multiple roles of cyclooxygenase-2 in endometrial cancer.
AB  - Cyclooxygenase-2 (COX-2) plays a critical role not only in maintenance of the
      endometrium during the menstrual cycle, but also in the progression of
      endometrial cancer. The role of COX-2 in tumor growth and development is complex
      and multifaceted. This review presents evidence for the expression of COX-2 being
      linked to angiogenesis, tumor cell apoptosis, tumor cell growth, metastasis and
      local immunosuppression in cancer progression. It also outlines the
      clinicopathological and prognostic significance of COX-2 in endometrial cancer.

PMID- 16302727
TI  - Gc protein (vitamin D-binding protein): Gc genotyping and GcMAF precursor
      activity.
AB  - The Gc protein (human group-specific component (Gc), a vitamin D-binding protein
      or Gc globulin), has important physiological functions that include involvement
      in vitamin D transport and storage, scavenging of extracellular G-actin,
      enhancement of the chemotactic activity of C5a for neutrophils in inflammation
      and macrophage activation (mediated by a GalNAc-modified Gc protein (GcMAF)). In
      this review, the structure and function of the Gc protein is focused on
      especially with regard to Gc genotyping and GcMAF precursor activity. A
      discussion of the research strategy "GcMAF as a target for drug discovery" is
      included, based on our own research.

PMID- 16302728
TI  - Immunohistochemical staining of hedgehog pathway-related proteins in human
      thymomas.
AB  - The thymus plays an essential role in the maturing of progenitor cells to
      functional T cells. Recent studies suggest that the Hedgehog (Hh) signaling
      pathway contributes to this differentiation process. However, there is limited
      information concerning the expression of Hh pathway-related proteins (Hh
      proteins) in the human thymus. The staining of Hh proteins in the thymic
      epithelium of 26 surgically resected thymoma tissues was examined by
      immunohistochemistry. The staining of sonic Hh (Shh) correlated relatively well
      with the World Health Organization histological classification of thymoma. The
      higher the grade, the fainter the staining. However, no significant difference in
      Shh staining was found between normal and neoplastic epithelia. Interestingly,
      Gli1 staining in thymomas was significantly greater than that in normal thymus (p
      < 0.0001). Thus, some members of the Hh signaling pathway may contribute to the
      development of thymoma.

PMID- 16302729
TI  - Purification, characterization and biological significance of tumor-derived
      exosomes.
AB  - Exosomes are nanovesicles that are released into the extracellular environment
      during the fusion of multivesicular bodies with the plasma membrane. Exosomes
      released from dendritic cells, dexosomes, have several biological functions, for
      example as immunostimulants. Some tumor cells also secrete exosomes (Tu
      exosomes). Although experimental data obtained with the use of dexosomes suggest
      a biological function of Tu-exosomes, this still remains poorly understood. To
      examine the function of Tu-exosomes, we established a method for collecting
      highly purified Tu-exosomes, using paramagnetic beads coated with antibodies
      against tumor-specific proteins such as HER2/neu. With these antibody-coated
      beads (Ab-beads), it was possible to collect HER2-expressing Tu-exosomes of high
      purity. Tu-exosomes were also collected from malignant ascites, which contain
      exosomes secreted from various types of cells such as tumor cells, lymphoid cells
      and mesothelial cells. The isolation of Tu-exosomes was confirmed by FACS
      analysis. With regard to their biological functions, Tu-exosomes cultured with a
      human breast cancer cell line bound to the cell surface and increased tumor cell
      proliferation. These data indicate that Tu-exosomes may have physiological
      functions.

PMID- 16302730
TI  - Efficacy of immuno-cell therapy in patients with advanced pancreatic cancer.
AB  - BACKGROUND: Patients with advanced pancreatic carcinoma have a risk of relapse
      after primary therapy, and the prognosis for these patients remains bleak. The
      effect of immuno-cell therapy in advanced pancreatic carcinoma, with or without
      other standard therapies, was examined. PATIENTS AND METHODS: Forty-six patients
      with advanced pancreatic carcinoma, undergoing immuno-cell treatment, were
      evaluated. RESULTS: Of all the patients, those who received immuno-cell therapy
      alone accounted for 15.4% of partial response (PR), 23.1% of long-term stable
      disease (SD), 46.2% of SD and 15.4% of progressive disease (PD), and had a 50%
      survival time of 14.5 months. The respective values for the 28 patients
      undergoing immuno-cell therapy with gemcitabine were 10.7% of PR, 10.7% of long
      term SD, 32.1% of SD and 46.4% of PD, with a 50% survival time of 15.8 months;
      for 5 patients undergoing immuno-cell therapy with UFT or TS-1, the values were
      0% of PR, 0% of SD, 20.0% of SD and 80.0% of PD, with a 50% survival time of 16.1
      months. CONCLUSION: The combination of immuno-cell therapies with standard
      therapies may be effective in the short-term in patients with advanced pancreatic
      cancer. Long-term survival depends on the presence of metastases and the duration
      of coadministration with these standard therapies.

PMID- 16302731
TI  - Efficacy and feasibility of procarbazine, ranimustine and vincristine
      chemotherapy, and the role of surgical resection in anaplastic oligodendroglioma.
AB  - The safety, tolerance and preliminary efficacy of a chemotherapy regimen
      consisting of procarbazine (PCB), ranimustine (MCNU) and vincristine (VCR) were
      assessed for patients with newly diagnosed supratentorial anaplastic
      oligodendroglioma. MATERIALS AND METHODS: Between October 1999 and September
      2003, 5 patients were enrolled. The initial regimens were prescribed as adjuvant
      therapy in conjunction with radiotherapy following standard surgical treatment.
      All patients received a chemotherapy comprising ranimustine (100 mg/m2)
      intravenously on Day 1, procarbazine (60 mg/m2) on Days 8 to 21, and vincristine
      (1.4 mg/m2, maximum total 2 mg) on Days 8 and 29. The cycles were repeated every
      8 weeks until tumor progression was evident, or for a total of 6 cycles over a 1
      year period. The primary end-points were safety and tolerability, while the
      secondary end-point was overall survival. RESULTS: Five consecutive eligible
      patients were treated. Of the 4 evaluable patients, 3 partially responded to the
      treatment (PR), while 1 had a complete response (CR): all patients are still
      alive. However, 3 of the 5 patients showed relapse, with a time to tumor
      progression (TTP) of 50, 143 and 241 weeks, respectively. Two of these patients
      received combined treatment with carboplatin, etoposide and recombinant human
      mutant tumor necrosis factor-alpha at the first relapse. This regimen appeared to
      be safe and neither neurological toxicity, severe or life-threatening
      hematological toxicity, nor fatal toxicity (WHO Grade 4) were experienced.
      CONCLUSION: These results suggest that a chemotherapy regimen consisting of PCB,
      MCNU and VCR in this patient population seems to be safe and tolerable, and the
      response rate was high. Thus, wide resection with a risk of major neurological
      morbidity due to nearby functionally critical areas can be avoided. However,
      since the relapse rate was high, a second-line chemotherapy should be developed
      for anaplastic oligodendroglioma to improve the long-term control of the disease.

PMID- 16302732
TI  - Re-targeting of cytotoxic T lymphocytes and/or natural killer cells to CEA
      expressing tumor cells with anti-CEA antibody activity.
AB  - Cellular immunity, in which cytotoxic T lymphocytes (CTLs) and natural killer
      (NK) cells are main effector cells, plays an important role in the antitumor
      defense mechanism. T cell immunotherapy is based on the assumption that tumor
      antigen (TA) peptides are correctly presented by HLA class I molecules on target
      tumor cells, while NK cell immunotherapy is based on the hypothesis that cell
      surface TAs or ligands for NK receptors are widely expressed in tumor cells.
      However, human tumor cells are well known to often lose HLA class 1 molecules,
      and target cell ligands for NK receptors are not always expressed in human tumor
      cells. This altered HLA class 1 expression and non-ubiquitous distribution of NK
      receptor ligands constitute the major tumor escape mechanism facing tumor
      specific CTL and/or NK cell-mediated responses. These facts also indicate that it
      is not easy to eliminate the target tumors only by activating tumor-specific CTLs
      or NK cells. On the other hand, although the protective role of humoral immunity
      in cancer seems not to be imperative, it is easily confirmed by immunostaining
      whether or not antibody-recognized TAs such as carcinoembryonic antigen (CEA)
      exist on the cell surface of target tumor cells. Therefore, endowing CTLs or NK
      cells with antigen-binding specificity of anti-TA antibody is promising for re
      targeting the activities of these effector cells to tumor cells in an HLA
      independent manner. This mini-review provides a brief overview of the following
      four technologies for re-targeting CTLs or NK cells to CEA-expressing tumor cells
      with anti-CEA antibody activity: i) bispecific antibody technology, ii) antibody
      cytokine fusion protein technology, iii) chimeric immune receptor technology, and
      iv) antibody-HLA/peptide complex technology.

PMID- 16302733
TI  - Preparation of human IgG and IgM monoclonal antibodies for MK-1/Ep-CAM by using
      human immunoglobulin gene-transferred mouse and gene cloning of their variable
      regions.
AB  - For antibody-based therapy of cancer, monoclonal antibodies (mAbs) of human
      origin are superior to mouse, mouse/human chimeric or humanized mAbs, because of
      their minimum immunogenicity to humans and their efficient collaboration with
      human effector cells. In the present study, human mAbs were prepared against a
      pancarcinoma antigen, MK-1 (Ep-CAM), using a genetically-engineered mouse (KM
      mouse) that contains the human immunoglobulin genes. Spleen cells from KM mice,
      immunized with recombinant MK-1, were fused with P3-U1 mouse myeloma cells. Of 44
      anti-MK-1 clones analyzed, two were of IgG4 and the others of IgM clones.
      Although the two IgG4 clones were suggested to recognize the same antigenic
      determinant or two closely located determinants, their VK regions were encoded by
      different light-chain genes while their VH sequences were identical. The two IgG4
      and one of the IgM clones tested revealed antibody-dependent cell-mediated
      cytotoxicity and complement-dependent cytotoxicity, respectively, against MK-1
      expressing cells in vitro, suggesting that these fully human mAbs produced
      against MK-1 and their V-region genes, which are applicable for the preparation
      of engineered antibody fragments that may be useful for antibody-based therapy of
      cancer.

PMID- 16302734
TI  - Combined immunocell therapy using activated lymphocytes and monocyte-derived
      dendritic cells for malignant melanoma.
AB  - BACKGROUND: The beneficial effects of immunocell therapy, using either activated
      lymphocytes (ALs) or dendritic cells (DCs), in the treatment of melanoma has been
      demonstrated. DCs are professional antigen-presenting cells that induce cytotoxic
      T lymphocytes against tumor cells. DC therapy may be promising when combined with
      ALs. PATIENTS AND METHODS: Patients with advanced melanoma, who underwent
      immunocell therapy with both ALs and DCs, were reviewed. DCs were pulsed with
      tumor lysates, peptides or both. RESULTS: Side-effects were occasional slight
      fever and skin erythema. Among 8 of the 14 patients treated with immunocell
      therapy alone, 1 showed a mixed response (MR) and 1 prolonged stable disease
      (SD). In the remaining 6 patients treated with immunocell therapy and other
      conventional therapies, 1 CR, 1 MR and 1 prolonged SD for 24 months were
      observed. CONCLUSION: Combined immunocell therapy was well tolerated and showed a
      relatively high tumor response. This treatment may have therapeutic potential for
      some refractory malignancies.

PMID- 16302735
TI  - Innate-immune therapy for lung carcinoma based on tissue-macrophage activation
      with lipopolysaccharide.
AB  - BACKGROUND: Over the last decade, tumor-specific antigens have been discovered,
      but so far it has not been possible to use them as part of an effective acquired
      immunotherapy. This failure may be due to the fact that the expression of the MHC
      class 1 is low and in lung cancer cells is heterogeneous. Therefore, it may be
      advantageous to develop techniques that activate the antitumor mechanism of the
      innate immune system. An experimental model was developed for testing lung cancer
      therapies that are based on the stimulation of macrophages, which then activate
      innate immunity. MATERIALS AND METHODS: A549, a human lung adenocarcinoma cell
      line, was co-cultured with a rat macrophage cell line (NR8383), or a human
      macrophage cell line (THP 1) at the ratios of 1:1 or 1:5. The experiments were
      performed with lipopolysaccharide (LPS) or in its absence. The cytotoxicity rate
      to A549 cells was estimated over time using a dye-uptake method and the amount of
      lactate dehydrogenase released was measured. The amount of nitric oxide (NO)
      induced in the medium was assayed, because it may be a candidate as a useful
      cytotoxic factor. RESULTS: High cytotoxicity was observed to A549 cells when co
      cultured with NR8383 cells in the presence of LPS. This effect was not observed
      in the absence of LPS. Similar results, although to a lesser extent, were
      observed when A549 cells were co-cultured with THP-1 cells. A high concentration
      of NO was measured in the co-culture medium of A549 cells and NR8383 cells when
      LPS was present. CONCLUSION: The induction of cell death in lung cancer cells
      occurred after contact with macrophages that had been activated by LPS. The NO
      that was produced by macrophages in response to LPS was responsible for some of
      this effect.

PMID- 16302736
TI  - Expression levels of thymidine phosphorylase (TP) and dihydropyrimidine
      dehydrogenase (DPD) in patients with gastrointestinal cancer.
AB  - BACKGROUND: Thymidine phosphorylase (TP) is a key enzyme involved in pyrimidine
      nucleoside metabolism. Dihydropyrimidine dehydrogenase (DPD) is the major
      catabolic enzyme of 5-fluorouracil (5-FU). These are important enzymes in the
      pyrimidine salvage pathway and are considered to be key enzymes for determining
      the prognosis of patients with gastrointestinal cancer. In the present study, TP
      and DPD were quantified and evaluated in gastric and colorectal cancer. PATIENTS
      AND METHODS: In 111 cases of malignancy, including 30 gastric cancers and 81
      colorectal cancers, the expression levels of both TP and DPD in fresh-frozen
      samples from either tumor or adjacent normal tissue were quantified using enzyme
      linked immunosorbent assay (ELISA). The relationships between TP or DPD
      expression levels in tumor tissues or adjacent normal tissues and
      clinicopathological factors were evaluated. RESULTS: The TP expression levels in
      gastric or colorectal tumor tissues were found to be significantly higher than
      those in the adjacent normal tissue. Although the DPD expression levels in
      gastric tumor tissue were significantly higher than those in adjacent normal
      tissue, the DPD expression levels in colorectal tumor tissue were nearly
      identical to those in the adjacent normal tissue. The DPD expression levels in
      gastric tumor tissues were significantly higher than those in colorectal tumor
      tissues. The TP expression levels correlated significantly with the DPD
      expression levels in tumor or adjacent normal tissues. The DPD expression levels
      in tumor tissues significantly correlated with those in adjacent normal tissue.
      CONCLUSION: The difference in DPD expressions between gastric and colorectal
      cancer tissues may reflect the organ specificity of the carcinomas and a
      difference in chemotherapeutic sensitivity to 5-FU or its analogs. The
      correlation between TP and DPD expression levels suggests the existence of a
      common regulatory pathway.

PMID- 16302737
TI  - Anti-allergic Psidium guajava extracts exert an antitumor effect by inhibition of
      T regulatory cells and resultant augmentation of Th1 cells.
AB  - Th1 polarization is one of the mechanisms underlying the therapeutic effects of
      herbal medicine. The action of anti-allergic agents from Psidium guajava (P.
      guajava) on T cell immunity in mice was investigated. The addition of P. guajava
      extracts blocked IL-10-mediated, in vitro induction of T regulatory (Tr) cells
      from CD4+ splenocytes of C57BL/6 mice, whereas the extracts exerted only a weak
      or no effect on the development of Th1 and Th2 cells. Accordingly, Tr cells were
      not induced from splenocytes of mice administered orally with the extracts.
      Furthermore, P. guajava extracts shifted the Th1/Th2 balance to a Th1 dominant
      status by directly attenuating Tr cell activity. In a study of tumor immunity,
      mice pretreated with the extracts exhibited retarded growth of s.c. inoculated
      B16 melanoma cells. These findings suggest that P. guajava extracts are
      efficacious for the prevention of tumor development by depressing Tr cells and
      subsequently shifting to Th1 cells.

PMID- 16302738
TI  - Combination therapy with tumor cell-pulsed dendritic cells and activated
      lymphocytes for patients with disseminated carcinomas.
AB  - This phase I study was performed to assess the safety and immune response of
      tumor cell-pulsed dendritic cell (DC) vaccine therapy against cancer patients
      with multiple metastases. DCs, generated from adherent cells of peripheral blood
      mononuclear cells (PBMCs) using interleukin-4 (IL-4) and granulocyte/monocyte
      colony-stimulating factor, were loaded with autologous necrotic whole tumor
      cells. Thereafter, the DCs were matured with culture supernatants of OK-432
      stimulated PBMCs. Activated lymphocytes were also induced from non-adherent cells
      of PBMCs using OKT-3 and IL-2. Patients received a subcutaneous injection of DCs
      loaded with tumor cells every 2 weeks and received an intravenous injection of
      activated lymphocytes every 4 weeks. This combination therapy was named tumor
      pulsed DC vaccine therapy. Tumor-pulsed DC vaccine therapy was continued as long
      as possible in 19 patients. No particular adverse reactions, except for low-grade
      fever, were found. The patients could be divided into two groups according to the
      survival time, i.e., 6 responders (long survival patients) and 13 non-responders
      (short survival patients). Based on the laboratory data of responders,
      eligibility criteria were determined. Using the eligibility criteria, a phase
      I/II study was recently performed with 15 patients. A delayed-type
      hypersensitivity reaction against tumor-pulsed DCs became positive in 13 of the
      15 patients within 6 months after the therapy. This therapy was again safe, and
      no evidence of autoimmune disease was noted. The survival time of these 15
      patients was significantly prolonged compared with that of the 13 non-responders
      of the phase I study (p < 0.0001). This continuous tumor-pulsed DC vaccine
      therapy was well tolerated in patients with disseminated carcinomas.

PMID- 16302739
TI  - Reveal protein molecular structural-chemical differences between two types of
      winterfat (forage) seeds with physiological differences in low temperature
      tolerance using synchrotron-based Fourier transform infrared microspectroscopy.
AB  - Winterfat (Krascheninnikovia lanata) (forage seed) is a long-lived native shrub
      with superior forage quality for livestock and wildlife. The objectives of this
      study were to use advanced synchrotron technology [S-Fourier transform infrared
      microspectroscopy (FTIR)] as a novel approach to reveal protein molecular
      structural-chemical differences in terms of protein secondary structures between
      the two types of winterfat (forage) seeds, which show physiological differences
      in low-temperature tolerances. This experiment was performed at beamline U10B at
      the National Synchrotron Light Source (NSLS) in Brookhaven National Laboratory
      (BNL), U.S. Department of Energy (NSLS-BNL, New York). The results showed that
      with the synchrotron analytical technique (S-FTIR), the molecular structural
      chemical makeup and characteristics of the winterfat seed tissues could be imaged
      and revealed. The protein secondary structures differed between the large and the
      small seed tissues. By using the multicomponent peaks modeling method, the
      results show that the large seeds contained no significant differences (P > 0.05)
      in percentage of beta-sheet (average 37.0%) and alpha-helix (average 24.1%).
      However, the large seeds contained a lower (P < 0.05) percentage of beta-turns
      (18.1 vs 20.1%) and a lower (P < 0.05) ratio of beta-turns to alpha-helices (0.8
      vs 0.9) and beta-turns to beta-sheets (0.5 vs 0.6). Our results demonstrate the
      potential of highly spatially resolved synchrotron-based FTIR microspectroscopy
      to reveal differences of structural molecular chemistry and protein secondary
      structures, which are associated with seed size variation and may affect
      germination behaviors.

PMID- 16302740
TI  - Microchemical structure of soybean seeds revealed in situ by ultraspatially
      resolved synchrotron Fourier transformed infrared microspectroscopy.
AB  - The distribution of water in soybean seeds during imbibition varies with the
      chemical composition of the tissue. To understand the dynamics of imbibition, the
      proteins, lipids, and carbohydrates of the cotyledons and hilum region in mature
      soybean seeds were mapped using synchrotron Fourier transformed infrared
      microspectroscopy, based on characteristic peaks for each component: amide I at
      1650 cm(-1) and amide II at 1550 cm(-1) for protein, lipid ester stretch at 1545
      cm(-1), and the region from 1200 to 900 cm(-1) for carbohydrates. The amount and
      configuration of the proteins varied across the cotyledon, as well as the amount
      of lipid and carbohydrate. It was found that protein distribution across the
      cotyledon is similar to water distribution during imbibition. The chemistry of
      the hilum region was also studied, as this is the point of water entry, and
      differences in the chemical composition of the tissues studied were observed.

PMID- 16302741
TI  - Event specific qualitative and quantitative polymerase chain reaction detection
      of genetically modified MON863 maize based on the 5'-transgene integration
      sequence.
AB  - Because of the genetically modified organisms (GMOs) labeling policies issued in
      many countries and areas, polymerase chain reaction (PCR) methods were developed
      for the execution of GMO labeling policies, such as screening, gene specific,
      construct specific, and event specific PCR detection methods, which have become a
      mainstay of GMOs detection. The event specific PCR detection method is the
      primary trend in GMOs detection because of its high specificity based on the
      flanking sequence of the exogenous integrant. This genetically modified maize,
      MON863, contains a Cry3Bb1 coding sequence that produces a protein with enhanced
      insecticidal activity against the coleopteran pest, corn rootworm. In this study,
      the 5'-integration junction sequence between the host plant DNA and the
      integrated gene construct of the genetically modified maize MON863 was revealed
      by means of thermal asymmetric interlaced-PCR, and the specific PCR primers and
      TaqMan probe were designed based upon the revealed 5'-integration junction
      sequence; the conventional qualitative PCR and quantitative TaqMan real-time PCR
      detection methods employing these primers and probes were successfully developed.
      In conventional qualitative PCR assay, the limit of detection (LOD) was 0.1% for
      MON863 in 100 ng of maize genomic DNA for one reaction. In the quantitative
      TaqMan real-time PCR assay, the LOD and the limit of quantification were eight
      and 80 haploid genome copies, respectively. In addition, three mixed maize
      samples with known MON863 contents were detected using the established real-time
      PCR systems, and the ideal results indicated that the established event specific
      real-time PCR detection systems were reliable, sensitive, and accurate.

PMID- 16302742
TI  - Excitation-emission fluorescence spectroscopy combined with three-way methods of
      analysis as a complementary technique for olive oil characterization.
AB  - This paper shows the potential of excitation-emission fluorescence spectroscopy
      (EEFS) and three-way methods of analysis [parallel factor analysis (PARAFAC) and
      multiway partial least-squares (N-PLS) regression] as a complementary technique
      for olive oil characterization. The fluorescence excitation-emission matrices of
      a set of Spanish extra virgin, virgin, pure, and olive pomace oils were measured,
      and the relationship between them and some of the quality parameters of olive
      oils (peroxide value, K232, and K270) was studied. N-PLS was found to be more
      suitable than PARAFAC combined with multiple linear regression for correlating
      fluorescence and quality parameters, yielding better fits and lower prediction
      errors. The best results were obtained for predicting K270. EEFS allowed
      detection of extra virgin olive oils highly degraded at early stages (with high
      peroxide value) and little oxidized pure olive oils (with low K270). The proposed
      methodology may be used as an aid to analyze doubtful samples.

PMID- 16302743
TI  - Efficient analysis of egg yolk proteins and their thermal sensitivity using
      sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing and
      nonreducing conditions.
AB  - The multiple functional properties of egg yolk are mostly influenced by its
      complex protein composition. The high lipid content of egg yolk as well as the
      low solubility of delipidated egg yolk lipoproteins make analysis by conventional
      chromatographic or electrophoretic techniques a difficult task. This work
      describes a method to profile egg yolk proteins after delipidation with acetone
      using sodium dodecyl sulfate polyacrylamide gel electrophoresis on precast 8-18%
      T polyacrylamide gradient gels. Twenty bands were obtained for the whole egg yolk
      profile with molecular weights ranging between 5 and 221 kDa. The bands were
      identified based on their molecular weight and by comparison with isolated egg
      yolk subfractions. The dissociation behavior under reducing and nonreducing
      conditions provided additionally helpful information for identification and
      characterization of the yolk proteins. The method presented is very well suited
      for assaying the thermal sensitivity of whole yolk and its components and thus
      for the characterization of heat treatment processes.

PMID- 16302744
TI  - Near-infrared spectroscopy in saffron quality control: determination of chemical
      composition and geographical origin.
AB  - Near-infrared reflectance spectroscopy has been applied for the first time to
      saffron spice to determine the chemical composition and geographical origin of
      111 samples from the there main producers' countries: Iran, Greece, and Spain.
      The validation procedures with the results obtained by UV-vis and HPLC-DAD
      measurements demonstrated that this technique is appropriate to determine the
      following parameters: moisture and volatile content, coloring strength, (250 nm),
      and (330 nm), established on the ISO 3632 Technical Specification Normative and
      used to certify saffron quality in the international market. Also, it can be used
      to estimate the content of the five main crocetin glycosides, the compounds
      responsible for saffron color, the best correlations being for trans-crocetin di
      (beta-D-gentibiosyl) ester (R2= 0.93), trans-crocetin (beta-D-glucosyl)-(beta-D
      gentibiosyl) (R2= 0.94), and picrocrocin (R2= 0.92), the compound accepted as
      responsible for saffron bitterness. Finally, a discriminant analysis among the
      three geographical origins reveals that Iranian samples are the most different,
      whereas Greek and Spanish samples are more similar. All of these results reveal
      that NIRS spectroscopy has an enormous potential for its application to saffron
      quality control as the results are obtained in 2 min and without any sample
      manipulation.

PMID- 16302745
TI  - Quantification of lignans in food using isotope dilution gas chromatography/mass
      spectrometry.
AB  - The optimization and validation of a protocol for the quantification of six
      dietary lignans, i.e., secoisolariciresinol, matairesinol, lariciresinol,
      pinoresinol, medioresinol, and syringaresinol, in food are presented. The method
      incorporates isotope dilution to ensure correct accuracy and precision,
      introducing the utilization of individual stable 13C3-labeled lignans. To
      demonstrate the potential of this new method, preliminary results of the levels
      of dietary lignans in selected foods are presented. It is concluded that the
      method fulfils the reliability criteria and can be applied to the analysis of the
      most common lignans in human food, being an essential asset to establish the
      intake of lignans in a determined population and their relation with disease
      prevention.

PMID- 16302746
TI  - Accelerated solvent extraction of ochratoxin a from rice samples.
AB  - In this paper, accelerated solvent extraction (ASE) for the analysis of
      ochratoxin A (OTA) is applied for the first time. Optimization of the method is
      given for the extraction of OTA from rice samples. Several parameters such as
      type of solvent, temperature, pressure, static time, and cell size were
      investigated thoroughly to find the optimal extraction conditions. The optimum
      ASE operating conditions were methanol as extraction solvent, 1500 psi, 40
      degrees C, 5 min of static time, 50% flush volume, 60 s of purge, 1 cycle, and 11
      mL cell size. The total extraction time was approximately 15 min. OTA was
      determined by liquid chromatography coupled with a fluorescence detector and
      confirmed by methyl ester derivatization. The analytical performance of the
      method was monitored with quality control parameters. Finally, the optimized
      method was used to evaluate 12 rice samples, 1 of which was positive with an OTA
      content of 4.17 ng/g. The proposed method offers the possibility of a fast and
      simple process to obtain a quantitative extraction of OTA.

PMID- 16302747
TI  - Highly sensitive enzyme-linked immunosorbent assay for chlorpyrifos. Application
      to olive oil analysis.
AB  - Highly sensitive enzyme-linked immunoassays for chlorpyrifos, one of the most
      applied insecticides, are presented. Several haptens were synthesized for
      immunoreagent production and ELISA development. The best immunoassays obtained
      are based on an indirect coated-plate immunoassay format. Two assays were
      optimized; one shows a limit of detection of 0.3 ng L(-1), an I50 of 271 ng L(
      1), and a dynamic range between 4 and 16 474 ng L(-1). The other one has a limit
      of detection of 0.07 ng L(-1), an I50 of 7 ng L(-1), and a dynamic range between
      0.4 and 302 ng L(-1). The assays were used to quantify chlorpyrifos in olive oil
      using a simple and rapid sample extraction procedure. The good recoveries
      achieved in both assays (109% mean value) and the agreement with values given by
      the GC reference method (110% mean value) indicate their potential for either
      screening or laboratory quantification.

PMID- 16302748
TI  - Origin of French virgin olive oil registered designation of origins predicted by
      chemometric analysis of synchronous excitation-emission fluorescence spectra.
AB  - The authentication of virgin olive oil samples requires usually the use of
      sophisticated and very expensive analytical techniques, so there is a need for
      fast and inexpensive analytical techniques for use in a quality control
      methodology. Virgin olive oils present an intense fluorescence spectra.
      Synchronous excitation-emission fluorescence spectroscopy (SEEFS) was assessed
      for origin determination of virgin olive oil samples from five French registered
      designation of origins (RDOs) (Nyons, Vallee des Baux, Aix-en-Provence, Haute
      Provence, and Nice). The spectra present bands between 600 and 700 nm in emission
      due to chlorophylls a and b and pheophytins a and b. The bands between 275 and
      400 nm in emission were attributed to alpha-, beta-, and gamma-tocopherols and to
      phenolic compounds, which characterize the virgin olive oils compared to other
      edible oils. The chemometric treatment (PLS1) of synchronous excitation-emission
      fluorescence spectra allows one to determine the origin of the oils from five
      French RDOs (Baux, Aix, Haute-Provence, Nice, and Nyons). Results were quite
      satisfactory, despite the similarity between two denominations of origin (Baux
      and Aix) that are composed by some common cultivars (Aglandau and Salonenque).
      The interpretation of the regression coefficients shows that RDOs are correlated
      to chlorophylls, pheophytins, tocopherols, and phenols compounds, which are
      different for each origin. SEEFS is part of a global analytic methodology that
      associates spectroscopic and chromatographic techniques. This approach can be
      used for traceability and vindicates the RDOs.

PMID- 16302749
TI  - Identification of isolutein (lutein epoxide) as cis-antheraxanthin in orange
      juice.
AB  - The carotenoid profile of orange juice is very complex, a common characteristic
      for citrus products in general. This fact, along with the inherent acidity of the
      product, which promotes the isomerization of some carotenoids, makes the correct
      identification of some of these pigments quite difficult. Thus, one of the
      carotenoids occurring in orange juice has been traditionally identified as
      isolutein, a term used to refer to lutein epoxide, although enough evidence to
      support that identification has not been given. In this study, the carotenoid
      previously identified as isolutein/lutein epoxide in orange juice has been
      isolated and identified as a 9 or 9'-cis isomer of antheraxanthin as a result of
      different tests. To support this identification, a mixture of geometrical isomers
      of lutein epoxide isolated from petals of dandelions was analyzed under the same
      conditions used for orange juice carotenoids to check that neither their
      retention times nor their spectroscopic features matched with those of the orange
      juice carotenoid now identified as a cis isomer of antheraxanthin.

PMID- 16302750
TI  - Evaluation of supercritical fluid extraction/aminopropyl solid-phase "in-line"
      cleanup for analysis of pesticide residues in rice.
AB  - Supercritical fluid extraction (SFE) and the use of aminopropyl solid-phase
      material for "in-line" cleanup was evaluated for residue analysis of 22 GC
      amenable pesticides in wild- and white-rice samples with a fat content of 1.9 and
      0.4%, respectively. After optimizing the extraction conditions on glass beads as
      inert material and evaluating the fat amount extracted from rice by SFE, the use
      of Florisil, Celite, Extrelut, Hydromatrix, and an aminopropyl material as fat
      retention materials for SFE "in-line" cleanup was assessed, aminopropyl being the
      most suitable material for this cleanup of fat. Pesticide mean recoveries
      obtained from rice samples, at fortification levels around 0.5 mg/kg, by means of
      the SFE/in-line cleanup method finally proposed (15-mL CO2 volume, 50 degrees C
      temperature, 200 atm pressure, 200 muL of methanol static modifier, and a 1-cm
      layer of aminopropyl at the bottom of the extraction vessel), ranged between 74
      and 98%, except for captafol and dimethoate for which mean recoveries lower than
      21% were determined.

PMID- 16302751
TI  - Stable isotope characterization of the ortho-oxygenated phenylpropanoids:
      coumarin and melilotol.
AB  - The natural abundance 2H NMR spectra of extractive coumarin 10 and of its
      dihydroderivative melilotol 11 produced by baker's yeast reduction has been
      compared with synthetic materials. Diagnostic for the differentiation of 10 are
      the (D/H)beta values, which are in the 128.1-133.6 ppm interval for the natural
      compounds but 258.5 and 189.8 ppm for the synthetic materials. Such a dramatic
      difference is also found for methyl cinnamate 12, which shows (D/H)beta values of
      127.2 and 515.8 ppm, respectively. In extractive 10, the ratio
      (D/H)4para/(D/H)6ortho = 1.24 is similar to that observed in structurally related
      salicin and methyl salicylate. Coumarin 10 is transformed in salicyl alcohol 9,
      providing diacetate 14, showing in the natural series the trend (D/H)3meta >
      (D/H)4para > (D/H)5meta approximately (D/H)6ortho. A similar trend is shown also
      by the synthetic 10. A clear distinction between extractive and synthetic 10 is
      obtained through delta18O determinations on 10 and on chroman 13. The bulk
      delta18O values in the extractive series of 10 are 20.3, 23.6, and 22.6 per
      thousand, while those of the aromatic oxygen are 2.3, 0.5, and -0.5 per thousand.
      In the synthetic sample, the values are 12.6 and 5.6 per thousand, respectively.
      As a final product, the reduction of 10 leads to the dihydroderivative 11. Both
      the baker's yeast reduction and the catalytic hydrogenation lead to a marked
      decrease of the deuterium content of 11, which is stronger for the beta-position
      than for the alpha-position.

PMID- 16302752
TI  - Use of electrochemical biosensor and gas chromatography for determination of
      dichlorvos in wheat.
AB  - Two methods for the determination of dichlorvos in durum wheat by electrochemical
      assay and gas chromatography, respectively, have been developed. Dichlorvos, an
      organophosphorus anticholinesterase pesticide, was extracted from wheat with
      hexane, and the filtered extract was directly analyzed by gas chromatography with
      nitrogen-phosphorus flame detection (NPD). Recoveries of dichlorvos from milled
      wheat spiked at 0.25-1.5 microg/g ranged from 96.5 to 100.9%, and the limit of
      detection was 0.02 microg/g. The electrochemical assay was based on the detection
      of choline, the acetylcholinesterase product, via a choline oxidase biosensor. An
      aliquot of the filtered hexane extract was partitioned with phosphate buffer
      solution, and the organic layer was evaporated prior to electrochemical analysis.
      A limit of detection of 0.05 microg/g of dichlorvos was obtained with mean
      recoveries of 97-103% at spiking levels of 0.25-1.5 microg/g. A good correlation
      (r = 0.9919) was found between the results obtained with the electrochemical and
      those obtained with the gas chromatographic methods. The electrochemical method
      was peer-validated in two laboratories that analyzed 10 blind samples (5
      duplicates), including a blank and 4 spiked samples with dichlorvos at levels of
      0.25, 0.60, 1.00, and 1.50 microg/g. Within-laboratory repeatability (RSDr) and
      between-laboratory reproducibility (RSDR) ranged from 5.5 to 7.8% and from 9.9 to
      17.6%, respectively.

PMID- 16302753
TI  - Dietary fibers from mushroom sclerotia: 1. Preparation and physicochemical and
      functional properties.
AB  - Preparation of three novel dietary fibers (DFs) from mushroom sclerotia, namely,
      Pleurotus tuberregium, Polyporous rhinocerus, and Wolfiporia cocos, by a scale-up
      modified AOAC procedure using industrial enzymes was investigated. A remarkably
      high level of total dietary fiber (TDF) ranging from 81.7 to 96.3% sample dry
      matter (DM), in which a content of nonstarch polysaccharide (NSP) ranging from
      86.6 to 94.3% sclerotial TDF DM, was obtained from the three sclerotia. All
      sclerotial DFs were rich in beta-glucan (the glucose residue ranged from 89.7 to
      94.5% NSP DM) with a very low level of resistant glycogen (ranged from 3.77 to
      3.94% sclerotial TDF DM). All three novel sclerotial DFs also exhibited similar,
      if not better, physicochemical and functional properties (pH, color, water
      binding capacity, oil holding capacity, and emulsifying properties) as those of
      barely DF control and commercial DF-rich ingredients. The potential use of the
      three mushroom sclerotial DFs as a new beta-glucan type DF-rich ingredient in the
      food industry was discussed.

PMID- 16302754
TI  - Dietary fibers from mushroom Sclerotia: 2. In vitro mineral binding capacity
      under sequential simulated physiological conditions of the human gastrointestinal
      tract.
AB  - The in vitro mineral binding capacity of three novel dietary fibers (DFs)
      prepared from mushroom sclerotia, namely, Pleurotus tuber-regium, Polyporous
      rhinocerus, and Wolfiporia cocos, to Ca, Mg, Cu, Fe, and Zn under sequential
      simulated physiological conditions of the human stomach, small intestine, and
      colon was investigated and compared. Apart from releasing most of their
      endogenous Ca (ranged from 96.9 to 97.9% removal) and Mg (ranged from 95.9 to
      96.7% removal), simulated physiological conditions of the stomach also attenuated
      the possible adverse binding effect of the three sclerotial DFs to the exogenous
      minerals by lowering their cation-exchange capacity (ranged from 20.8 to 32.3%)
      and removing a substantial amount of their potential mineral chelators including
      protein (ranged from 16.2 to 37.8%) and phytate (ranged from 58.5 to 64.2%). The
      in vitro mineral binding capacity of the three sclerotial DF under simulated
      physiological conditions of small intestine was found to be low, especially for
      Ca (ranged from 4.79 to 5.91% binding) and Mg (ranged from 3.16 to 4.18%
      binding), and was highly correlated (r > 0.97) with their residual protein
      contents. Under simulated physiological conditions of the colon with slightly
      acidic pH (5.80), only bound Ca was readily released (ranged from 34.2 to 72.3%
      releasing) from the three sclerotial DFs, and their potential enhancing effect on
      passive Ca absorption in the human large intestine was also discussed.

PMID- 16302755
TI  - Dietary fibers from mushroom sclerotia: 3. In vitro fermentability using human
      fecal microflora.
AB  - The in vitro fermentability of three novel dietary fibers (DFs) prepared from
      mushroom sclerotia, namely, Pleurotus tuber-regium, Polyporous rhinocerus, and
      Wolfiporia cocos, was investigated and compared with that of the cellulose
      control. All DF samples (0.5 g each) were fermented in vitro with a human fecal
      homogenate (10 mL) in a batch system (total volume, 50 mL) under strictly
      anaerobic conditions (using oxygen reducing enzyme and under argon atmosphere) at
      37 degrees C for 24 h. All three novel sclerotial DFs exhibited notably higher
      dry matter disappearance (P. tuber-regium, 8.56%; P. rhinocerus, 13.5%; and W.
      cocos, 53.4%) and organic matter disappearance (P. tuber-regium, 9.82%; P.
      rhinocerus, 14.6%; and W. cocos, 57.4%) when compared with those of the cellulose
      control. Nevertheless, only the W. cocos DF was remarkably degraded to produce
      considerable amounts of total short chain fatty acids (SCFAs) (5.23 mmol/g DF on
      organic matter basis, with a relatively higher molar ratio of propionate) that
      lowered the pH of its nonfermented residue to a slightly acidic level (5.89).
      Variations on the in vitro fermentability among the three sclerotial DFs might
      mainly be attributed to their different amounts of interwoven hyphae present
      (different amounts of enzyme inaccessible cell wall components) as well as the
      possible different structural arrangement (linkage and degree of branching) of
      their beta-glucans.

PMID- 16302756
TI  - Synergistic antioxidative effects of alkamides, caffeic acid derivatives, and
      polysaccharide fractions from Echinacea purpurea on in vitro oxidation of human
      low-density lipoproteins.
AB  - Preparations of Echinacea are widely used as alternative remedies to prevent the
      common cold and infections in the upper respiratory tract. After extraction,
      fractionation, and isolation, the antioxidant activity of three extracts, one
      alkamide fraction, four polysaccharide-containing fractions, and three caffeic
      acid derivatives from Echinacea purpurea root was evaluated by measuring their
      inhibition of in vitro Cu(II)-catalyzed oxidation of human low-density
      lipoprotein (LDL). The antioxidant activities of the isolated caffeic acid
      derivatives were compared to those of echinacoside, caffeic acid, and rosmarinic
      acid for reference. The order of antioxidant activity of the tested substances
      was cichoric acid > echinacoside > or = derivative II > or = caffeic acid > or =
      rosmarinic acid > derivative I. Among the extracts the 80% aqueous ethanolic
      extract exhibited a 10 times longer lag phase prolongation (LPP) than the 50%
      ethanolic extract, which in turn exhibited a longer LPP than the water extract.
      Following ion-exchange chromatography of the water extract, the majority of its
      antioxidant activity was found in the latest eluted fraction (H2O-acidic 3). The
      antioxidant activity of the tested Echinacea extracts, fractions, and isolated
      compounds was dose dependent. Synergistic antioxidant effects of Echinacea
      constituents were found when cichoric acid (major caffeic acid derivative in E.
      purpurea) or echinacoside (major caffeic acid derivative in Echinacea pallida and
      Echinacea angustifolia) were combined with a natural mixture of alkamides and/or
      a water extract containing the high molecular weight compounds. This contributes
      to the hypothesis that the physiologically beneficial effects of Echinacea are
      exerted by the multitude of constituents present in the preparations.

PMID- 16302757
TI  - Humic substances can modulate the allelopathic potential of caffeic, ferulic, and
      salicylic acids for seedlings of lettuce (Lactuca sativa L.) and tomato
      (Lycopersicon esculentum Mill.).
AB  - The capacity of a leonardite humic acid (LHA), a soil humic acid (SHA), and a
      soil fulvic acid (SFA) in modulating the allelopathic potential of caffeic acid
      (CA), ferulic acid (FA), and salicylic acid (SA) on seedlings of lettuce (Lactuca
      sativa L.) and tomato (Lycopersicon esculentum Mill.) was investigated. Lettuce
      showed a sensitivity greater than that of tomato to CA, FA, and SA phytotoxicity,
      which was significantly reduced or even suppressed in the presence of SHA or SFA,
      especially at the highest dose, but not LHA. In general, SFA was slightly more
      active than SHA, and the efficiency of the action depended on their
      concentration, the plant species and the organ examined, and the allelochemical.
      The daily measured residual concentration of CA and FA decreased drastically and
      that of SA slightly in the presence of germinating seeds of lettuce, which were
      thus able to absorb and/or enhance the degradation of CA and FA. The adsorption
      capacity of SHA for the three allelochemicals was small and decreased in the
      order FA > CA > SA, thus suggesting that adsorption could be a relevant
      mechanism, but not the only one, involved in the "antiallelopathic" action.

PMID- 16302758
TI  - Novel chemotaxonomic markers of the Alternaria infectoria species-group.
AB  - Two new structurally related metabolites, novae-zelandin A (1) and novae-zelandin
      B (2), as well as the novel metabolite 4Z-infectopyrone (3) were purified from
      extracts of filamentous fungi belonging to the Alternaria infectoria species
      group. The structures were elucidated by a combination of 1D and 2D NMR
      spectroscopic data and MS data. 1-3 are important chemotaxonomic markers of the
      A. infectoria species-group and exhibit structures similar to those of known
      biologically active compounds, suggesting that they could be potential
      phytotoxins.

PMID- 16302759
TI  - Phytosterol composition of nuts and seeds commonly consumed in the United States.
AB  - Phytosterols were quantified in nuts and seeds commonly consumed in the United
      States. Total lipid extracts were subjected to acid hydrolysis and then alkaline
      saponfication, and free sterols were analyzed as trimethylsilyl derivatives by
      capillary GC-FID and GC-MS. Delta5-Avenasterol was quantified after alkaline
      saponification plus direct analysis of the glucoside. Sesame seed and wheat germ
      had the highest total phytosterol content (400-413 mg/100 g) and Brazil nuts the
      lowest (95 mg/100 g). Of the products typically consumed as snack foods,
      pistachio and sunflower kernel were richest in phytosterols (270-289 mg/100 g).
      beta-Sitosterol, Delta5-avenasterol, and campesterol were predominant.
      Campestanol ranged from 1.0 to 12.7 mg/100 g. Only 13 mg/100 g beta-sitosterol
      was found in pumpkin seed kernel, although total sterol content was high (265
      mg/100 g). Phytosterol concentrations were greater than reported in existing food
      composition databases, probably due to the inclusion of steryl glycosides, which
      represent a significant portion of total sterols in nuts and seeds.

PMID- 16302760
TI  - Chemistry and phytotoxicity of thaxtomin A alkyl ethers.
AB  - The thaxtomin phytotoxins (1 and 2) from scab-producing Streptomyces pathogens of
      the potato are 2,5-dioxopiperazines consisting of modified l-tryptophanyl and l
      phenylalanyl units. Thaxtomin A (1) is hydroxylated at C-14, the alpha carbon of
      the modified l-phenylalanyl moiety. Refluxing thaxtomin A in acidified MeOH,
      EtOH, and i-PrOH afforded C-14 thaxtomin A methyl- (3a and 3b), ethyl- (4a and
      4b), and isopropyl- (5a and 5b) ethers, respectively, in both the 11S,14R (3a,
      4a, and 5a) and 11S,14S (3b, 4b, and 5b) configurations. Crystal structures were
      determined for 3a and 4a. Extensive NMR as well as other spectroscopic data
      supported structural assignments for all of the derivatives. The 11S,14R
      configured derivatives were slightly less potent than the natural products (1 and
      2) as inhibitors of lettuce seedling root growth, whereas the activity of the
      11S,14S epimers was much reduced, indicating that the configuration at C-14 found
      in the naturally occurring thaxtomins is essential for biological activity. Among
      the 11S,14R-configured compounds, potency decreased with an increasing size of
      the substituted alkoxy group.

PMID- 16302761
TI  - Determination of the chemical composition and antioxidant activity of the
      essential oil of Artemisia dracunculus and of the antifungal and antibacterial
      activities of Turkish Artemisia absinthium, A. dracunculus, Artemisia santonicum,
      and Artemisia spicigera essential oils.
AB  - The essential oil isolated from Turkish tarragon (Artemisia dracunculus) by
      hydrodistillation was analyzed by GC-MS. Thirty compounds representing 99.5% of
      total oil were identified. The predominant components in the oil were (Z)
      anethole (81.0%), (Z)-beta-ocimene (6.5%), (E)-beta-ocimene (3.1%), limonene
      (3.1%), and methyleugenol (1.8%). The antibacterial and antifungal activities of
      the essential oils isolated from A. dracunculus, Artemisia absinthium, Artemisia
      santonicum, and Artemisia spicigera oils were also evaluated. In general, the
      oils exhibited potent antifungal activity at a wide spectrum on the growth of
      agricultural pathogenic fungi. Among the oils, the weakest antifungal activity
      was shown by the oil of A. dracunculus. In many cases, the oils of A. absinthium,
      A. santonicum, and A. spicigera completely inhibited the growth of some fungal
      species. As compared with antibacterial activities of all of tested oils, A.
      santonicum and A. spicigera oils showed antibacterial activities over a very wide
      spectrum. However, the essential oils tested showed lower inhibition zones than
      the inhibition zones of penicillin. In addition, antioxidant and 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radical scavenging activities of tarragon oil were
      determined, and weak antioxidant and DPPH radical scavenging activities were
      found in comparison to butylated hydroxytoluene.

PMID- 16302762
TI  - Flavonoids in baby spinach (Spinacia oleracea L.): changes during plant growth
      and storage.
AB  - The variation in flavonoid concentration and composition was investigated in baby
      spinach (Spinacia oleracea L.) cv. Emilia sown on three occasions, each harvested
      at three growth stages at 6-day intervals. After harvest, leaves were stored in
      polypropylene bags at 2 or 10 degrees C. Flavonoids were analyzed by reversed
      phase HPLC. Twelve flavonoid peaks were detected. The main flavonoid, making up
      on average 43% of the total flavonoid concentration, was identified as 5,3',4'
      trihydroxy-3-methoxy-6:7-methylenedioxyflavone-4'-glucuronide. Four other
      flavonoids each contributed 7-12% of the total flavonoid content. Total flavonoid
      content was relatively stable during normal retail storage conditions, although
      some of the individual flavonoid compounds showed considerable variation. The
      youngest plants had the highest flavonoid concentration, indicating that by
      harvesting the baby spinach a few days earlier than the current commercial stage
      of harvest, the flavonoid concentration in the product may be increased and the
      content of potentially health-promoting compounds enhanced.

PMID- 16302763
TI  - Antioxidant characterization of some Sicilian edible wild greens.
AB  - Epidemiological studies have demonstrated that many antioxidants and the total
      antioxidant capacity (TAC) of the diet may protect against cancers and
      cardiovascular disease. Common fruits and vegetables are good sources of
      antioxidants, although in some Mediterranean areas traditional wild greens are
      responsible for a significant percentage of total dietary antioxidant intake. In
      the European Prospective Investigation into Cancer and Nutrition cohort of Ragusa
      (Sicily), a high number of subjects were found to frequently eat wild greens,
      including Sinapis incana and Sinapis nigra, Diplotaxis erucoides, Cichorium
      intybus, Asparagus acutifolius, and Borrago officinalis. On the basis of these
      observations, detailed characterization of single antioxidant components (i.e.,
      polyphenols, carotenoids, chlorophylls, and ascorbic acid) and the TAC of these
      edible wild traditional plants was performed. The wild plants examined were found
      to be very rich in antioxidants, such as flavonoids and carotenoids, with high
      TAC values, suggesting that the importance of these vegetables, not only in the
      traditional but even in the contemporary diet, needs to be emphasized.

PMID- 16302764
TI  - Nasunin from eggplant consists of cis-trans isomers of delphinidin 3-[4-(p
      coumaroyl)-L-rhamnosyl (1-->6)glucopyranoside]-5-glucopyranoside.
AB  - Two major anthocyanins were isolated from the acidified methanolic extract of
      eggplant (Solanum melongena L.) by column chromatography and preparative high
      performance liquid chromatography. These anthocyanins were interconvertible under
      room light illumination condition. By means of tandem time-of-flight mass
      spectrometry and nuclear magnetic resonance spectroscopy, their structures were
      identified and elucidated as delphinidin 3-[4-(cis-p-coumaroyl)-l-rhamnosyl(1-
      >6)glucopyranoside]-5-glucopyranoside (compound 1) and delphinidin 3-[4-(trans-p
      coumaroyl)-l-rhamnosyl-(1-->6)glucopyranoside]-5-glucopyranoside (compound 2),
      respectively. The results indicated that nasunin comprised cis and trans isomers
      of the p-coumaric acid moiety in its structure.

PMID- 16302765
TI  - Stability of tea polyphenol (-)-epigallocatechin-3-gallate and formation of
      dimers and epimers under common experimental conditions.
AB  - (-)-Epigallocatechin-3-gallate (EGCG), the most abundant and biologically active
      compound in tea, has been extensively studied for its activities related to
      disease prevention in animal models and in vitro. However, its stability under
      different experimental conditions has not been well-characterized. In the present
      study, the stability of EGCG in animal drinking fluid and under cell culture
      conditions and the factors that affect its stability under these conditions were
      investigated. Our results demonstrated that auto-oxidation and epimerization are
      the two major reactions causing the instability of EGCG. The structures of the
      major oxidation products, EGCG dimers, were identified. The rates of these
      reactions were affected by the temperature, pH, the partial pressure of oxygen,
      the level of antioxidants, the concentration of EGCG, and other components of
      tea. In future studies with EGCG, its stability should be considered in order to
      avoid possible artifacts.

PMID- 16302766
TI  - Synthesis of diethylamine-functionalized soybean oil.
AB  - Specialty chemicals based on renewable resources are desirable commodities due to
      their eco-friendly nature and "green" product characteristics. These chemicals
      can demonstrate physical and chemical properties comparable to those of
      conventional petroleum-based products. Suitably functionalized amines in the
      triacylglycerol structure can function as an antioxidant, as well as an
      antiwear/antifriction agent. In addition, the amphiphilic nature of seed oils
      makes them an excellent candidate as base fluid. The reaction of amine and
      epoxidized seed oils in the presence of a catalyst almost always leads to
      different intra/intermolecular cross-linked products. In most cases, the
      triacylglycerol structure is lost due to disruption of the ester linkage.
      Currently, there is no reported literature describing the aminolysis of vegetable
      oil without cross-linking. Here the epoxy group of the epoxidized soybean oil has
      been selectively reacted with amines to give amine-functionalized soybean oil.
      The optimization procedure involved various amines and catalysts for maximum
      aminolysis, without cross-linking and disruption of the ester linkage.
      Diethylamine and ZnCl2 were found to be the best. NMR, IR, and nitrogen analysis
      were used to characterize the products.

PMID- 16302767
TI  - Examination of 1,5-anhydro-D-fructose and the enolone ascopyrone P, metabolites
      of the anhydrofructose pathway of glycogen and starch degradation, for their
      possible application in fruits, vegetables, and beverages as antibrowning agents.
AB  - The anhydrofructose pathway describes the degradation of glycogen and starch to
      1,5-anhydro-D-fructose (1,5AnFru) and its further conversion to the enolone
      ascopyrone P (APP) via the transit intermediate ascopyrone M. The two products,
      1,5AnFru and APP, were examined in this study for their effects in controlling
      the browning of selected fruits, vegetables, and beverages. The results showed
      that 1,5AnFru had an antibrowning effect in green tea and was able to slow
      turbidity development in black currant wine. APP proved to be an antibrowning
      agent comparable to kojic acid. It showed an antibrowning effect in a range of
      agricultural products, such as various cultivars of apple, pear, potato, lettuce,
      and varieties of green tea in an efficacy concentration range from 300 to 500
      ppm. Mechanism studies indicated that, like kojic acid, APP showed inhibition
      toward plant polyphenol oxidase and was able to decolor quinones.

PMID- 16302768
TI  - Laccases of Pleurotus sapidus: characterization and cloning.
AB  - Peanut shells, a major waste stream of food processing, served as a renewable
      substrate for inducing the production of laccases by basidiomycetes. Of 46
      surface cultures examined, 29 showed laccase activity under the experimental
      conditions. The edible fungus Pleurotus sapidus was selected as the most active
      producer, immobilized on the shells, and cultivated in the fed-batch mode. A
      continuous rise in laccase activity was found, indicating the inducibility of
      laccase secretion by the peanut shells and the reusability of the mycelium. Two
      laccase isoenzymes were purified by decoupled 2-D electrophoresis, and amino acid
      sequence information was obtained by electrospray ionization tandem mass
      spectrometry. cDNAs of the corresponding gene and another laccase were cloned and
      sequenced using a PCR-based screening of a synthesized P. sapidus cDNA library.
      Data bank searches against public databases returned laccases of P. ostreatus and
      P. sajor-caju as the best hits. The potential use of laccases by the food
      industry is discussed.

PMID- 16302769
TI  - Pectinesterase inhibitor from jelly-fig (Ficus awkeotsang Makino) achenes reduces
      methanol content in carambola wine.
AB  - Crude pectinesterase (PE) inhibitor (PEI) extracted from jelly-fig achenes (JFA)
      (Ficus awakeosang Makino) was added to carambola (Averrhoa carambola L.) puree to
      determine the change in methanol production during fermentation. Addition of
      pectin or microbial pectic enzyme to puree increased dose-dependently the
      methanol content in fermented products. Decreasing ratio (from 1:0 to 1:19, v:v)
      of pectic enzyme to diluted crude PEI solution in the puree-enzyme mixture
      decreased the PE activity remarkably. Except for transmittance (%T), addition of
      crude PEI to puree did not affect apparently the physical and chemical properties
      of wine; however, it reduced methanol content in the control from 256 to 58 ppm.
      The degree of esterification (DE) of pectin in starting puree was approximately
      70%. It decreased to approximately 27% in the control group and reduced slightly
      to approximately 67% in fermented puree with crude PEI added after 14 days of
      fermentation. This reveals that crude PEI solution was potent in inhibiting
      intrinsic carambola PE activity and appeared to be a potential alternative for
      methanol reduction in wines.

PMID- 16302770
TI  - Effects of heating and illumination on trans-cis isomerization and degradation of
      beta-carotene and lutein in isolated spinach chloroplasts.
AB  - The influence of thermal treatment and light exposure on degradation and
      isomerization of the predominant carotenoids (lutein and beta-carotene) occurring
      in green leafy vegetables was assessed. The effect of lipid addition on
      carotenoid stability was also evaluated. For the first time, the stabilities of
      pure carotenoids and chloroplast-bound carotenoids were compared. Besides
      degradation, heating caused carotenoid isomerization in all samples. Whereas pure
      carotenoids favor 13-cis isomers, in native chloroplasts and heated chloroplasts
      9-cis isomers were predominant. Illumination of freshly prepared chloroplast
      isolates caused an initial increase in the level of lutein (9.6%) and beta
      carotene (29.8%), while pure carotenoids exhibited time-dependent degradation.
      The addition of lipids to chloroplast preparations had the reverse effects on the
      retention of both carotenoids after heating; isomerization was not significantly
      affected. It was demonstrated that carotenoid stability has to be evaluated for
      every individual pigment in its genuine environment. Stability data based on
      model systems (e.g., pure carotenoids) may not be transferred to complex food
      matrices without intensive investigation.

PMID- 16302771
TI  - Effect of high-intensity pulsed electric fields processing and conventional heat
      treatment on orange-carrot juice carotenoids.
AB  - Liquid chromatography (LC) was the method of choice for quantification of
      carotenoids (including geometrical isomers) to evaluate the effects of high
      intensity pulsed electric field (HIPEF), a nonthermal preservation method, with
      different parameters (electric field intensities and treatment times), on an
      orange-carrot juice mixture (80:20, v/v). In parallel, a conventional heat
      treatment (98 degrees C, 21 s) was applied to the juice. HIPEF processing
      generally caused a significant increase in the concentrations of the carotenoids
      identified as treatment time increased. HIPEF treatment at 25 and 30 kV/cm
      provided a vitamin A concentration higher than that found in the pasteurized
      juice.

PMID- 16302772
TI  - Pigments in the fruit of red-fleshed kiwifruit (Actinidia chinensis and Actinidia
      deliciosa).
AB  - Kiwifruit cultivars (Actinidia chinensis and A. deliciosa) generally have fruit
      with yellow or green flesh when ripe. A small number of genotypes also have red
      pigments, usually restricted to the inner pericarp but varying in intensity and
      in distribution within the fruit. Carotenoids, chorophylls, and anthocyanins were
      extracted from the fruit pericarp of such red-fleshed kiwifruit selections.
      Pigments were analyzed by HPLC and identified by comparison with authentic
      standards and by liquid chromatography-mass spectroscopy to obtain a tentative
      identification of the major anthocyanins in red-fleshed kiwifruit. The yellow and
      green colors of the outer fruit pericarp are due to different concentrations and
      proportions of carotenoids and chlorophylls. The red color found mainly in the
      inner pericarp is due to anthocyanins. In the A. chinensis genotypes tested the
      major anthocyanin was cyanidin 3-O-xylo(1-2)-galactoside, with smaller amounts of
      cyanidin 3-O-galactoside. In the A. deliciosa genotypes analyzed, cyanidin 3-O
      xylo(1-2)-galactoside was not detected; instead, the major anthocyanins
      identified were cyanidin 3-O-galactoside and cyanidin 3-O-glucoside. However, the
      two species did not differ consistently in anthocyanin composition.

PMID- 16302773
TI  - Determination of anthocyanins from camu-camu (Myrciaria dubia) by HPLC-PDA, HPLC
      MS, and NMR.
AB  - Camu-camu [Myrciaria dubia (HBK) McVaugh] is a small fruit native to the
      Amazonian rain forest. Its anthocyanin profile has now been investigated for the
      first time. Fruits from two different regions of the Sao Paulo state, Brazil,
      were analyzed. The major anthocyanins were isolated by high-speed countercurrent
      chromatography. HPLC-PDA, HPLC-MS/MS, and 1H NMR were used to confirm the
      identity of the main anthocyanins of camu-camu. Cyanidin-3-glucoside was
      identified as the major pigment in the fruits from both regions, representing
      89.5% in the fruits produced in Iguape and 88.0% in those from Mirandopolis,
      followed by the delphinidin-3-glucoside, ranging between 4.2 and 5.1%,
      respectively. Higher total anthocyanin contents were detected in the fruits from
      Iguape (54.0 +/- 25.9 mg/100 g) compared to those from Mirandopolis (30.3 +/- 6.8
      mg/100 g), most likely because of the lower temperatures in the Iguape region.

PMID- 16302774
TI  - Disposition of selected flavonoids in fruit tissues of various tomato
      (lycopersicon esculentum mill.) Genotypes.
AB  - Flavonoids have been studied extensively because they offer great potential
      health benefits. In this study, enzymatic hydrolysis of glycosylated quercetin,
      kaempferol, and naringin was used to obtain their sugar-free aglycones. The
      investigation also employed a validated HPLC method to obtain the chiral
      disposition of the aglycone naringenin enantiomers. These analyses were conducted
      on exocarp, mesocarp, and seed cavity tissues of field-grown tomato (Lycopersicon
      esculentum Mill.) mutants (anthocyanin absent, atroviolacea, and high pigment-1)
      and their nearly isogenic parent (cv. Ailsa Craig) at immature green, "breaker",
      and red ripe maturity stages. Concentrations of all flavonoids using enzymatic
      hydrolysis were significantly higher than previously reported concentrations
      using acid hydrolysis. Presumably, this occurred due to a more specific and rapid
      hydrolysis of the glycoside moiety by the beta-glucosidase enzyme. The glycoside
      S-naringin was the predominant enantiomer in all fruit tissues, although the
      aglycones free R- and S-naringenin were detected in both exocarp and mesocarp.
      Whereas there was significantly more quercetin than kaempferol in exocarp tissue,
      they were present in about equal concentrations in the mesocarp. Quercetin
      concentrations were higher in the exocarp and mesocarp of immature green and
      breaker fruit of the high pigment-1 mutant than in the other genotypes,
      supporting the observed photoprotection and potential health benefits of the high
      pigment-1 tomato genotype.

PMID- 16302776
TI  - Characterization of dietary fiber lignins from fruits and vegetables using the
      DFRC method.
AB  - Insoluble fiber fractions from 11 fruits and vegetables were investigated for
      their lignin composition using the derivatization followed by reductive cleavage
      (DFRC) methodology. To enrich lignin contents and to minimize polysaccharide
      excess that led to nonanalyzable DFRC chromatograms, the insoluble fibers were
      degraded by a carbohydrolases mixture. The residues that were found to be
      representative for the insoluble fiber lignins were analyzed. The investigated
      fibers differ considerably in their lignin contents and also in their lignin
      compositions. With the exception of radish fiber, only trace amounts (or none) of
      the products resulting from p-hydroxyphenyl units were detected. Lignins
      noticeably differed in the ratio of the DFRC products resulting from syringyl
      units (S) and guaiacyl (G) units (G/S ratios ranged from approximately 39 to
      0.2). The insoluble fiber lignins were classified as G-rich lignins (G/S ratio >
      3; carrot, spinach, kiwi, curly kale, radish, and asparagus), S-rich lignins (S/G
      ratio > 3; rhubarb), or balanced lignins (0.3 < G/S ratio < 3; pear, apple, small
      radish, and kohlrabi). Information about further structural characteristics, for
      example, cinnamyl endgroups, was obtained from the analysis of DFRC minor
      products.

PMID- 16302775
TI  - Characterization and quantitation of phenolic compounds in new apricot (Prunus
      armeniaca L.) varieties.
AB  - Thirty-seven apricot varieties, including four new releases (Rojo Pasion,
      Murciana, Selene, and Dorada) obtained from different crosses between apricot
      varieties and three traditional Spanish cultivars (Currot, Mauricio, and Bulida),
      were separated according to flesh color into four groups: white, yellow, light
      orange, and orange (mean hue angles in flesh were 88.1, 85.0, 77.6, and 72.4,
      respectively). Four phenolic compound groups, procyanidins, hydroxycinnamic acid
      derivatives, flavonols, and anthocyanins, were identified by HPLC-MS/MS and
      individually quantified using HPLC-DAD. Chlorogenic and neochlorogenic acids,
      procyanidins B1, B2, and B4, and some procyanidin trimers, quercetin 3
      rutinoside, kaempferol 3-rhamnosyl-hexoside and quercetin 3-acetyl-hexoside,
      cyanidin 3-rutinoside, and 3-glucoside, were detected and quantified in the skin
      and flesh of the different cultivars. The total phenolics content, quantified as
      the addition of the individual compounds quantified by HPLC, ranged between 32.6
      and 160.0 mg 100 g(-1) of edible tissue. No correlation between the flesh color
      and the phenolic content of the different cultivars was observed.

PMID- 16302777
TI  - Phenolic extraction from apple peel by cellulases from Thermobifida fusca.
AB  - With the optimization of the pretreatment conditions for the crude Thermobifida
      fusca cellulase activity and phenolic release from apple peel, we focused on the
      activity of individual purified cellulase related to the antioxidant activity.
      The overall phenolic release was significantly increased in a synergistic manner
      with combined pretreatment, not with individual pretreatment such as boiling,
      acid, and pectinase treatment. Approximately 60 mg of reducing sugar equivalent
      were produced per g of apple peel by treatment with T. fusca crude extract, and
      up to 3 times more reducing sugars were released when the apple peel was boiled
      and then treated with acid and pectinase. There was good correlation between the
      release of phenolics and reducing sugar by cellulase treatment and also between
      the amount of total phenolics and antioxidant capacity by each enzyme treatment
      (r2> 0.95). Among the tested enzymes purified from T. fusca cell extract,
      cellulase activity on apple peel was the highest with cellulase 6A (Cel 6A; 43%
      digestion), and the highest antioxidant capacity was obtained by incubation with
      Cel 6B (16 mg vitamin C equiv/g). Synergism in the activity was found from the
      combined treatment with Cel 6A and 6B in both cellulase activity and antioxidant
      capacity after 20 h of incubation. Cel 9A (progressive endocellulase) exhibited
      greater cellulase activity and antioxidant capacity than Cel 9A cd which lacks in
      cellulose-binding module, indicating that the cellulose-binding domain might play
      important roles in cellulolysis of apple peel. This study could provide some
      insights into the action mechanism of various cellulases on the digestion of
      cellulose-containing byproducts and expand the opportunity for cellulase
      utilization in the extraction of functional ingredients from the plant-derived
      byproducts.

PMID- 16302778
TI  - Synthesis and herbicidal evaluation of novel 3-[(alpha-hydroxy
      substituted)benzylidene]pyrrolidine-2,4-diones.
AB  - A series of 3-[(alpha-hydroxy-substituted) benzylidene]pyrrolidine-2,4-dione
      derivatives were synthesized as candidate herbicides by reacting different aroyl
      acetates with N-substituted glycine esters. The new compounds were identified by
      1H NMR spectroscopy and elemental analyses. Their herbicidal activities were
      evaluated. Some compounds exhibited excellent herbicidal activities at a dose of
      187.5 g/ha. A suitable electron-donating substituent at the 2- and/or 4-position
      of the phenyl ring was essential for high herbicidal activity, a result that has
      not been reported before. It was also found that the title compound's structure
      activity relationships were different from those of other similar kinds of
      earlier compounds, a result that may depend on the enol structure difference.

PMID- 16302779
TI  - Degradation of alachlor in natural and sludge-amended soils, studied by gas and
      liquid chromatography coupled to mass spectrometry (GC-MS and HPLC-MS).
AB  - Alachlor [2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)acetamide] is an
      herbicide used worldwide. The relative rates of disappearance of alachlor, the
      formation kinetics of alachlor ethane sulfonic acid (ESA), and the formation of
      other degradation products in two different soils (a soil with natural organic
      matter and a sludge-amended soil) has been studied. For such a purpose, soil
      samples were spiked with alachlor at 2.5 mg kg(-1), concentration generally
      applied in agricultural soils, and were submitted to sunlight, simulating natural
      field conditions. Extracts were analyzed by GC-MS and HPLC-MS in scan mode. A
      good correlation was observed between both techniques, and HPLC-MS allowed the
      determination of two eluting peaks corresponding to the two stereoisomeric forms
      of alachlor ESA. Degradation of alachlor in the two soils followed first-order
      kinetics. Half-life in the natural soil was 4.2 +/- 0.1 days, and half-life in
      the sludge-amended soil was 5.8 +/- 0.8 days. The higher half-life observed in
      the sludge-amended soil was attributed to the higher sorption of alachlor to this
      soil compared to the natural soil. The degradation of alachlor in both soils gave
      rise to the production of alachlor ESA. Its concentration increased during the
      incubation period, and after 27 days, its concentration was about 0.59 mg kg(-1)
      in the natural soil and 0.37 mg kg(-1) in the sludge-amended soil. The other two
      alachlor transformation products were identified using GC-MS, and the abundance
      of these degradation products increased while alachlor was degraded.

PMID- 16302780
TI  - Carbonyl odorants contributing to the in-oven roast beef top note.
AB  - Among the few papers related to the gas chromatography (GC)-olfactometric
      determination of important odorants in cooked beef aroma, only one uses roasting
      conditions, but none of them investigates the appealing aroma during the cooking
      of the piece of meat. The present paper investigates this top note as perceived
      from the oven, by analyzing the oven headspace using GC-"SNIF", a GC
      olfactometric technique. From the different functional classes of odorants
      participating in overall in-oven aroma, this first paper focuses only on the role
      of aldehydes and ketones, as they represent the majority of aroma compounds
      formed during cooking. To ascertain the identification of these odorants, a
      microderivatization technique was used, based on (2,3,4,5,6
      pentafluorophenyl)hydrazine. The resulting hydrazones exhibit very specific mass
      spectrometric fragments, leading to a sensitive and specific detection. A total
      of 23 carbonyl compounds were shown to contribute to the roast beef top note.

PMID- 16302781
TI  - Production of natural methyl anthranilate by microbial N-demethylation of N
      methyl methyl anthranilate by the topsoil-isolated bacterium Bacillus megaterium.
AB  - Bacillus megaterium, isolated in a screening process from topsoil, was used for N
      demethylation of natural N-methyl methyl anthranilate to produce natural methyl
      anthranilate. Maximal productivity of 70 mg/L/day was achieved under laboratory
      scale conditions without further optimization. No byproducts were observed. Thus,
      production of "natural" methyl anthranilate using B. megaterium is a significant
      improvement over comparable already existing procedures.

PMID- 16302782
TI  - Pressure-induced unfolding and aggregation of the proteins in whey protein
      concentrate solutions.
AB  - Whey protein concentrate solutions (12% w/v, pH 6.65 +/- 0.05) were pressure
      treated at 800 MPa for 20-120 min and then examined using size exclusion
      chromatography (SEC), small deformation rheology, transmission electron
      microscopy, and various types of one-dimensional (1D) and two-dimensional (2D)
      polyacrylamide gel electrophoresis (PAGE). The pressure-treated samples showed a
      time-dependent loss of native whey proteins by SEC and 1D PAGE and a
      corresponding increase in non-native proteins and protein aggregates of different
      sizes. These aggregates altered the viscosity and opacity of the samples and were
      shown to be cross-linked by intermolecular disulfide bonds and by noncovalent
      interactions using 1D PAGE [alkaline (or native), sodium dodecyl sulfate (SDS),
      and SDS of reduced samples (SDS(R))] and 2D PAGE (native:SDS and SDS:SDS(R)). The
      sensitivity of the major whey proteins to pressure was in the order beta
      lactoglobulin B (beta-LG B) > beta-LG A > bovine serum albumin (BSA) > alpha
      lactalbumin (alpha-LA), and the large internal hydrophobic cavity of beta-LG may
      have been partially responsible for its sensitivity to high-pressure treatments.
      It seemed likely that, at 800 MPa, the formation of a beta-LG disulfide-bonded
      network preceded the formation of disulfide bonds between alpha-LA or BSA and
      beta-LG to form multiprotein aggregates, possibly because the disulfide bonds of
      alpha-LA and BSA are less exposed than those of beta-LG either during or after
      pressure treatment. It may be possible that intermolecular disulfide bond
      formation occurred at high pressure and that hydrophobic association became
      important after the high-pressure treatment.

PMID- 16302783
TI  - Protective effects of synthetic hydroxytyrosol acetyl derivatives against
      oxidative stress in human cells.
AB  - Chemically stable di- and triacetyl derivatives of the natural o-diphenol
      antioxidant hydroxytyrosol were synthesized, and their chemical and biological
      antioxidant activities were assessed in comparison with that of the native
      synthetic compound. The chemical antioxidant activity of the selected compounds
      was evaluated by measuring the ferric reducing antioxidant power (FRAP). The data
      clearly indicate that, as expected, the hydroxytyrosol analogues, modified in the
      o-diphenolic ring, are devoid of any chemical antioxidant activity. On the
      contrary, both acetyl derivatives, at micromolar concentrations, equally protect
      against tert-butylhydroperoxide-induced oxidative damages in Caco-2 cells and
      human erythrocytes. This paper for the first time reports that chemically stable
      hydroxytyrosol acetyl derivatives, although devoid of chemical antioxidant
      activity, are as effective as the parent compound in protecting human cells from
      oxidative stress-induced cytotoxicity, after metabolization by esterases at the
      intestinal level, suggesting their possible utilization in either nutritional
      (functional food), cosmetic, or pharmaceutical preparations.

PMID- 16302784
TI  - Synthesis of carbonated fatty methyl esters using supercritical carbon dioxide.
AB  - The two-step syntheses of the cyclic carbonates carbonated methyl oleate (CMO)
      and carbonated methyl linoleate (CML) are reported. First, synthesis of epoxides
      through well-precedented chemical reactions of unsaturated fatty methyl esters
      with hydrogen peroxide and formic acid was accomplished. Next, a carbonation
      reaction with a simple tetrabutylammonium bromide catalyst was performed,
      allowing the direct incorporation of carbon dioxide into the oleochemical. These
      syntheses avoid the use of the environmentally unfriendly phosgene. The
      carbonated products are characterized by IR, 1H NMR, and 13C NMR spectroscopy and
      studied by thermogravimetric analysis (TGA). Also reported is the synthesis of a
      similar cyclic carbonate from the commercially available 2-ethylhexyl epoxy
      soyate. These carbonates show properties that may make them useful as
      petrochemical replacements or as biobased industrial product precursors.

PMID- 16302785
TI  - Direct spectrophotometric determination of bitterness in virgin olive oil without
      prior isolation by pH gradient.
AB  - Bitter taste, an organoleptic characteristic of virgin olive oil, has been
      related to phenolic compound composition. The usual method to assess this
      attribute is by a sensorial panel of tasters, while in the laboratory; methods
      based on physicochemical properties have been assayed as K225, the most widely
      used one. However, a direct determination of bitterness in virgin olive oil is
      useful for quality-control purposes. The proposed method is supported by the
      observable spectral change undergone by the compounds responsible for bitterness
      as pH varied. This measurement was carried out directly in the oil, without prior
      isolation of bitter analytes. The difference of absorbance between alkaline and
      neutral medium showed a highly significant correlation (r = 0.988, p < 0.0001)
      with the conventional parameter (K225). The method was rapid, required a small
      sample, allowed direct determination of bitterness in virgin olive oil, and could
      be easily automated.

PMID- 16302786
TI  - Isomerization of trans-astaxanthin induced by copper(II) ion in ethanol.
AB  - Carotenoids are unstable and susceptible to disruption by environmental factors
      such as heat, light, and solvents. However, there is little information on the
      effect of metal ions on stability of carotenoids, especially those essential
      elements in human nutrition. Astaxanthin is one of the few carotenoids containing
      four oxygen donors. Usually, these oxygen donors can coordinate with heavy metal
      ions such as Cu(II) and Fe(III). In the present study, the interaction of trans
      astaxanthin with Cu(II) was examined. It was found that Cu(II) markedly induces
      the conversion of trans-astaxanthin to its cis forms, which mainly consist of 9
      cis-astaxanthin and 13-cis-astaxanthin as suggested by UV-visible spectra and
      HPLC measurements. Increasing either incubation time of Cu(II) and trans
      astaxanthin in ethanol or the Cu(II)/astaxanthin ratio results in an increased
      percentage of cis isomers derived from trans-astaxanthin. All these results
      provide important information on the effects of dietary factors on the
      bioavailability and bioactivity of trans-astaxanthin.

PMID- 16302787
TI  - Impact of lipid physical state on the oxidation of methyl linolenate in oil-in
      water emulsions.
AB  - The purpose of this research was to examine the influence of the physical state
      of lipids on iron-promoted oxidation of methyl linolenate in octadecane oil-in
      water emulsions. Octadecane and methyl linolenate oil-in-water emulsions were
      prepared that contained droplets having the octadecane as either liquid or solid.
      The physical state of the octadecane was confirmed by a differential scanning
      calorimeter (DSC). The effect of the physical state of the lipid on oxidation
      rates was determined as a function of iron concentration (80 and 160 microM), pH
      (3.0 or 7.0), emulsifier type, and cooling rate. Oxidation of methyl linolenate
      was determined by lipid hydroperoxides and thiobarbituric acid reactive
      substances (TBARS). Emulsions containing solid octadecane had higher rates of
      lipid hydroperoxide and TBARS formation than those containing liquid octadecane.
      The rate at which the emulsions were cooled had no influence on oxidation rates.
      Oxidation rates in both emulsions increased with increasing iron concentration
      and decreasing pH. Oxidation rates were lowest in emulsions with cationic droplet
      membranes (dodecyl trimethylammonium bromide-stabilized), presumably due to the
      repulsion of iron from the oxidizable methyl linolenate in the emulsion droplet
      core. These results suggest that upon crystallization of octadecane, the liquid
      methyl linolenate migrated to the emulsion droplet surface, where it was more
      prone to oxidation because it was in closer contact with the iron ions in the
      aqueous phase.

PMID- 16302788
TI  - Conjugated linoleic acid-induced fatty liver can be attenuated by combination
      with docosahexaenoic acid in C57BL/6N mice.
AB  - We investigated the effect of dietary combination of conjugated linoleic acid
      (CLA) and docosahexaenoic acid (DHA) to attenuate CLA-induced fatty liver in
      C57BL/6N mice. Mice were fed semisynthetic diets that contained either 6% high
      linoleic safflower oil (HL-SAF), 4% HL-SAF + 2% CLA, or 3.5% HL-SAF + 2% CLA +
      0.5% DHA for 4 weeks. This 4 week feeding of CLA showed hepatic lipid
      accumulation concomitant with the decrease in adipose tissue weight in mice.
      However, 0.5% supplementation of DHA to the CLA diet could alleviate fatty liver
      without decreasing the antiobesity effect of CLA. The CLA diet promoted fatty
      acid synthesis in the liver, but DHA supplementation significantly attenuated the
      increase in enzyme activity induced by CLA. On the other hand, serum
      adipocytokines, leptin and adiponectin, were drastically decreased by CLA
      feeding, and DHA supplementation did not affect those levels. These results show
      that DHA supplementation to the CLA diet can attenuate CLA-induced fatty liver
      through the reduction of hepatic fatty acid synthesis without affecting
      adipocytokine production in C57BL/6N mice.

PMID- 16302789
TI  - Fumonisin mycotoxins in traditional Xhosa maize beer in South Africa.
AB  - The production and consumption of home-brewed Xhosa maize beer is a widespread
      traditional practice in the former Transkei region of South Africa. HPLC
      determination of fumonisins B1 (FB1), B2 (FB2), and B3 (FB3) in maize beer
      samples collected in two magisterial areas, Centane and Bizana, showed a wide
      range of levels. All samples were positive for FB(1), with a mean level of 281 +/
      262 ng/mL and a range from 38 to 1066 ng/mL. Total fumonisins (FB1 + FB2 + FB3)
      ranged from 43 to 1329 ng/mL, with a mean of 369 +/- 345 ng/mL. Data on the
      consumption of home-brewed beer are not available. On the basis of published data
      for the consumption of commercial beer in South Africa, the fumonisin exposure in
      these districts among the consumers of maize beer was found to be well above the
      provisional maximum tolerable daily intake of 2 mug/kg of body weight/day set by
      the Joint FAO/WHO Expert Committee on Food Additives.

PMID- 16302791
TI  - Heat shock protein 90 inhibitors. A text book example of medicinal chemistry?

PMID- 16302792
TI  - Rhodamine-labeled 2beta-carbomethoxy-3beta-(3,4-dichlorophenyl)tropane analogues
      as high-affinity fluorescent probes for the dopamine transporter.
AB  - Novel fluorescent ligands were synthesized to identify a high-affinity probe that
      would enable visualization of the dopamine transporter (DAT) in living cells.
      Fluorescent tags were extended from the N- or 2-position of 2beta-carbomethoxy
      3beta-(3,4-dichlorophenyl)tropane, using an ethylamino linker. The resulting 2
      substituted (5) and N-substituted (9) rhodamine-labeled ligands provided the
      highest DAT binding affinities expressed in COS-7 cells (Ki= 27 and 18 nM,
      respectively) in the series. Visualization of the DAT with 5 and 9 was
      demonstrated by confocal fluorescence laser scanning microscopy in stably
      transfected HEK293 cells.

PMID- 16302793
TI  - Discovery of a potent, orally available, and isoform-selective retinoic acid
      beta2 receptor agonist.
AB  - 4'-Octyl-4-biphenylcarboxylic acid (1g, AC-55649) was identified as a highly
      isoform-selective agonist at the human RARbeta2 receptor in a functional intact
      cell-based screening assay. The subsequent hit to lead optimization transformed
      the lipophilic, poorly soluble hit into a more potent and orally available
      compound (2, AC-261066) with retained beta2 selectivity and greatly improved
      physiochemical properties. Being an isoform-selective RARbeta2 receptor agonist
      that discriminates between nuclear receptor isoforms having identical ligand
      binding domains, 2 will be useful as a pharmacological research tool but also a
      valuable starting point for drug development.

PMID- 16302794
TI  - Design and synthesis of tri-ring P3 benzamide-containing aminonitriles as potent,
      selective, orally effective inhibitors of cathepsin K.
AB  - We have prepared a series of achiral aminoacetonitriles, bearing tri-ring
      benzamide moieties and an aminocyclohexanecarboxylate residue at P2. This
      combination of binding elements resulted in sub-250 pM, reversible, selective,
      and orally bioavailable cathepsin K inhibitors. Lead compounds displayed single
      digit nanomolar inhibition in vitro (of rabbit osteoclast-mediated degradation of
      bovine bone). The best compound in this series, 39n (CRA-013783/L-006235), was
      orally bioavailable in rats, with a terminal half-life of over 3 h. 39n was dosed
      orally in ovariectomized rhesus monkeys once per day for 7 days. Collagen
      breakdown products were reduced by up to 76% dose-dependently. Plasma
      concentrations of 39n above the bone resorption IC50 after 24 h indicated a
      correlation between functional cellular and in vivo assays. Inhibition of
      collagen breakdown by cathepsin K inhibitors suggests this mechanism of action
      may be useful in osteoporosis and other indications involving bone resorption.

PMID- 16302795
TI  - Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular
      potencies against off-target cathepsins and reduced functional selectivity.
AB  - The lysosomal cysteine protease cathepsin K is a target for osteoporosis therapy.
      The aryl-piperazine-containing cathepsin K inhibitor CRA-013783/L-006235 (1)
      displays greater than 4000-fold selectivity against the lysosomal/endosomal
      antitargets cathepsin B, L, and S. However, 1 and other aryl-piperazine
      containing analogues, including balicatib (10), are approximately 10-100-fold
      more potent in cell-based enzyme occupancy assays than against each purified
      enzyme. This phenomenon arises from their basic, lipophilic nature, which results
      in lysosomal trapping. Consistent with its lysosomotropic nature, 1 accumulates
      in cells and in rat tissues of high lysosome content. In contrast, nonbasic aryl
      morpholino-containing analogues do not exhibit lysosomotropic properties.
      Increased off-target activities of basic cathepsin K inhibitors were observed in
      a cell-based cathepsin S antigen presentation assay. No potency increases of
      basic inhibitors in a functional cathepsin K bone resorption whole cell assay
      were detected. Therefore, basic cathepsin K inhibitors, such as 1, suffer from
      reduced functional selectivities compared to those predicted using purified
      enzyme assays.

PMID- 16302796
TI  - Combining in silico tools and NMR data to validate protein-ligand structural
      models: application to matrix metalloproteinases.
AB  - A combination of in silico tools and experimental NMR data is proposed for
      relatively fast determination of protein-ligand structural models and
      demonstrated from known inhibitors of matrix metalloproteinases (MMP). The 15N 1H
      heteronuclear single quantum coherence (HSQC) spectral assignment and the 3D
      structure, either X-ray or NMR, are needed. In this method, the HSQC spectrum
      with or without the ligand is used to determine the interaction region of the
      ligand. Docking calculations are then performed to obtain a set of structural
      models. From the latter, the nuclear Overhauser effects (NOEs) between the ligand
      and the protein can be predicted. Guided by these predictions, a number of NOEs
      can be detected and assigned through a HSQC NOESY experiment. These data are used
      as structural restraints to reject/refine the initial structural models through
      further in silico work. For a test protein (MMP-12, human macrophage
      metalloelastase), a final structure of a protein-ligand adduct was obtained that
      matches well with the full structural determination. A number of structural
      predictions were then made for adducts of a similar protein (MMP-1, human
      fibroblast collagenase) with the same and different ligands. The quality of the
      final results depended on the type and number of experimental NOEs, but in all
      cases, a well-defined ligand conformation in the protein binding site was
      obtained. This protocol is proposed as a viable alternative to the many
      approaches described in the literature.

PMID- 16302797
TI  - 2-(Quinazolin-4-ylamino)-[1,4]benzoquinones as covalent-binding, irreversible
      inhibitors of the kinase domain of vascular endothelial growth factor receptor-2.
AB  - A series of 2-(quinazolin-4-ylamino)-[1,4] benzoquinone derivatives that function
      as potent covalent-binding, irreversible inhibitors of the kinase domain of
      vascular endothelial growth factor receptor-2 (VEGFR-2) has been prepared by
      ceric ammonium nitrate oxidation of substituted (2,5-dimethoxyphenyl)(6,7
      disubstituted-quinazolin-4-yl)amines and by displacement of the chlorine atom of
      substituted 2-chloro-5-(6,7-disubstituted-quinazolin-4-ylamino)
      [1,4]benzoquinones with various amines, anilines, phenols, and alcohols. Enzyme
      studies were conducted in the absence and presence of glutathione and plasma.
      Several of the compounds inhibit VEGF-stimulated autophosphorylation in intact
      cells. Kinetic experiments were performed to study the reactivity of selected
      inhibitors toward glutathione. Reactivities correlated with LUMO energies
      calculated as averages of those of individual conformers weighted by the
      Boltzmann distribution. These results and molecular modeling were used to
      rationalize the biological observations. The compounds behave as non-ATP
      competitive inhibitors. Unequivocal evidence, from mass spectral studies,
      indicates that these inhibitors form a covalent interaction with Cys-1045. One
      member of this series displays antitumor activity in an in vivo model.

PMID- 16302798
TI  - Crystal structures for HIV-1 reverse transcriptase in complexes with three
      pyridinone derivatives: a new class of non-nucleoside inhibitors effective
      against a broad range of drug-resistant strains.
AB  - In the treatment of AIDS, the efficacy of all drugs, including non-nucleoside
      inhibitors (NNRTIs) of HIV-1 reverse transcriptase (RT), has been limited by the
      rapid appearance of drug-resistant viruses. Lys103Asn, Tyr181Cys, and Tyr188Leu
      are some of the most common RT mutations that cause resistance to NNRTIs in the
      clinic. We report X-ray crystal structures for RT complexed with three different
      pyridinone derivatives, R157208, R165481, and R221239, at 2.95, 2.9, and 2.43 A
      resolution, respectively. All three ligands exhibit nanomolar or subnanomolar
      inhibitory activity against wild-type RT, but varying activities against drug
      resistant mutants. R165481 and R221239 differ from most NNRTIs in that binding
      does not involve significant contacts with Tyr181. These compounds strongly
      inhibit wild-type HIV-1 RT and drug-resistant variants, including Tyr181Cys and
      Lys103Asn RT. These properties result in part from an iodine atom on the
      pyridinone ring of both inhibitors that interacts with the main-chain carbonyl
      oxygen of Tyr188. An acrylonitrile substituent on R165481 substantially improves
      the activity of the compound against wild-type RT (and several mutants) and
      provides a way to generate novel inhibitors that could interact with conserved
      elements of HIV-1 RT at the polymerase catalytic site. In R221239, there is a
      flexible linker to a furan ring that permits interactions with Val106, Phe227,
      and Pro236. These contacts appear to enhance the inhibitory activity of R221239
      against the HIV-1 strains that carry the Val106Ala, Tyr188Leu, and Phe227Cys
      mutations.

PMID- 16302799
TI  - 3,6-disubstituted coumarins as mechanism-based inhibitors of thrombin and factor
      Xa.
AB  - In this work, coumarins were screened on thrombin (THR) and factor Xa (FXa), two
      of the most promising targets for the development of anticoagulant drugs. This
      allowed us to highlight compound 30, characterized by a 2,5-dichlorophenyl ester
      in the 3-position and a chloromethyl moiety in the 6-position, as a very potent
      THR inhibitor (ki/KI= 37,000 M(-1) s(-1)). Moreover, this compound exhibits good
      selectivity over FXa (168-fold) and trypsin (54-fold). The mechanism of
      inactivation was investigated in this series and significantly differs from that
      previously observed with alpha-chymotrypsin. Indeed, the addition of hydrazine on
      the THR-inhibitor complex promotes a partial induced THR reactivation. This
      reactivation, confirmed by LC/MS, showed the resurgence of the native THR and a
      new dihydrazide complex. Docking experiments were then efficiently used to
      explain the trends observed in the enzymatic assays as well as to corroborate the
      postulated inhibition mechanism. Finally, the cell permeability of our
      derivatives was estimated using a computational approach.

PMID- 16302800
TI  - Structural basis of inhibitor specificity of the human protooncogene proviral
      insertion site in moloney murine leukemia virus (PIM-1) kinase.
AB  - The kinase PIM-1 plays a pivotal role in cytokine signaling and is implicated in
      the development of a number of tumors. The three-dimensional structure of PIM-1
      is characterized by an unique hinge region which lacks a second hydrogen bond
      donor and makes it particularly important to determine how inhibitors bind to
      this kinase. We determined the structures of PIM-1 in complex with
      bisindolylmaleimide (BIM-1) and established the structure-activity relationship
      (SAR) for this inhibitor class. In addition, we screened a kinase targeted
      library and identified a number of high affinity inhibitors of PIM-1 such as
      imidazo[1,2-b]pyridazines, pyrazolo[1,5-a]pyrimidines, and members of the
      flavonoid family. In this paper we present an initial SAR of the identified
      scaffolds determined on the basis of a thermostability shift assay, calorimetric
      binding data, and biochemical assays which may find applications for the
      treatment of PIM-1 dependent cancer types.

PMID- 16302801
TI  - Pharmacophoric features of biguanide derivatives: an electronic and structural
      analysis.
AB  - The structure and electronic structure of drugs determine their mechanism of
      action. Correct structural representation of drugs helps in the proper
      identification of pharmacophoric features. Biguanide derivatives are a very
      important class of drugs, but their electronic structure was not clearly
      understood. Ab initio MO and density functional studies revealed the structure of
      the most stable tautomer of biguanide. (i) Electron delocalization, (ii) 1,3-H
      shift, (iii) 1,5-H shift, (iv) protonation, and (v) deprotonation processes,
      etc., have been investigated for biguanide. The molecular electrostatic potential
      (MESP) surfaces of neutral, protonated, and deprotonated biguanide have been
      shown to be similar in their most stable arrangements. The electrostatic
      potential of the complementary surface where these systems may bind also could be
      identified. Finally, the most stable structure of the important biguanide
      derivatives has been given after performing a conformational search.

PMID- 16302802
TI  - Preorganization of the hydroxyethylene dipeptide isostere: the preferred
      conformation in solution resembles the conformation bound to BACE.
AB  - Conformational analysis in solution of beta-secretase inhibitors 1 and 2 by NMR
      spectroscopy reveals that the hydroxyethylene isostere, an apparently flexible
      fragment widely used as a scissile bond replacement in aspartic protease
      inhibitors, exists in one predominant conformation in solution. This preferred
      conformation is similar to that adopted by the hydroxyethylene core of 1 in
      complex with beta-secretase and that adopted by hydroxyethylene cores of related
      compounds when bound to aspartic proteases, indicating that this structural unit
      is preorganized in solution.

PMID- 16302803
TI  - Identification of the structural requirements of the receptor-binding affinity of
      diphenolic azoles to estrogen receptors alpha and beta by three-dimensional
      quantitative structure-activity relationship and structure-activity relationship
      analysis.
AB  - Three-dimensional (3D) quantitative structure-activity relationship (QSAR) and
      structure-activity relationship (SAR) analyses were applied concurrently to a
      data set of highly selective estrogen receptor beta (ERbeta) agonists. The data
      set consisted of diphenolic azoles characterized by similar structural skeletons
      but with different binding modes to the estrogen receptor site. Models were
      developed separately with respect to the relative binding affinities (RBAs) to
      ERalpha and ERbeta. Steric and electrostatic fields were calculated for a
      training set of 72 compounds using comparative molecular field analysis (CoMFA).
      The model developed for ERalpha RBA yielded R2 of 0.91 and q(cv)2 of 0.60. The
      model developed for ERbeta RBA yielded R2 of 0.95 and q(cv)2 of 0.40. Both models
      were validated successfully using an external test set of 32 compounds. A new
      concept of test set evaluation based on the variability of the biological
      response due to the variability of the living organism has been introduced. The
      CoMFA analysis was supported by a SAR study. In addition to the most favorable
      steric and electrostatic regions identified by CoMFA, a number of structural
      descriptors were identified as being important for binding. These are the number
      of substituents attached to the main skeleton of each compound, the largest
      distance between the oxygen atoms of each molecule, and the angle defined by the
      planes that split the phenyl or the naphthyl and the benzisoxazole or the
      benzoxazole moiety in a morphometrically longitudinal way.

PMID- 16302804
TI  - N-benzylisatin sulfonamide analogues as potent caspase-3 inhibitors: synthesis,
      in vitro activity, and molecular modeling studies.
AB  - A number of isatin sulfonamide analogues were prepared and their potencies for
      inhibiting caspase-1, -3, -6, -7, and -8 were evaluated in vitro. Several
      compounds displaying a nanomolar potency for inhibiting the executioner caspases,
      caspase-3 and caspase-7, were identified. These compounds were also observed to
      have a low potency for inhibiting the initiator caspases, caspase-1 and caspase
      8, and caspase-6. Molecular modeling studies provided further insight into the
      interaction of this class of compounds with activated caspase-3. The results of
      the current study revealed a number of non-peptide-based caspase inhibitors that
      may be useful in assessing the role of inhibiting the executioner caspases in
      minimizing tissue damage in disease conditions characterized by unregulated
      apoptosis.

PMID- 16302806
TI  - Design, synthesis, and microbiological evaluation of new Candida albicans CYP51
      inhibitors.
AB  - In a program aimed at the design and synthesis of novel azole inhibitors of
      Candida albicans CYP51 (CA-CYP51), a series of azole 1,4-benzothiazines (BT) and
      1,4-benzoxazines (BO) were recently synthesized. A morphological study of the
      enzyme active site highlighted a hydrophobic access channel, and a docking study
      pointed out that the C-2 position of the BT or BO nucleus was oriented toward the
      access channel. Here, we report the design, synthesis, and microbiological
      evaluation of C-2-alkyl BT and BO compounds. In both series, introduction of the
      alkyl chain maintained and in some cases improved the anti-Candida in vitro
      activity; however, there was not always a strict correlation between in vitro and
      in vivo activity for several compounds.

PMID- 16302805
TI  - Doxazolidine, a proposed active metabolite of doxorubicin that cross-links DNA.
AB  - A crystal structure establishes doxoform as a dimeric formaldehyde conjugate of
      the oxazolidine of doxorubicin. Doxoform is a prodrug of doxazolidine, a
      monomeric doxorubicin formaldehyde-oxazolidine. Both doxoform and doxazolidine
      inhibit the growth of cancer cells at 1-4 orders of magnitude lower concentration
      than doxorubicin. They also inhibit the growth of cancer cells better than
      doxsaliform, a prodrug for an acyclic doxorubicin-formaldehyde conjugate.
      Doxoform rapidly hydrolyzes to doxazolidine, which then hydrolyzes to doxorubicin
      with a half-life of 3 min in human serum at 37 degrees C. Both doxoform and
      doxazolidine are taken up by multidrug-resistant MCF-7/Adr cells 3- to 4-fold
      better than doxorubicin. A molecular model suggests that doxazolidine can cross
      link DNA by direct reaction with a G-base in a tautomeric form with synchronous
      ring opening of the oxazolidine. These results point to doxoform being a prodrug
      for doxazolidine that is the reactive species that directly cross-links DNA.

PMID- 16302807
TI  - Conformationally constrained CCK4 analogues incorporating IBTM and BTD beta-turn
      mimetics.
AB  - To test whether a turnlike arrangement is involved in the bioactive conformation
      of CCK4 analogues upon CCK1 receptor recognition, we describe the preparation of
      two series of CCK4 derivatives, in which the central dipeptide Met-Asp has been
      replaced by recognized beta-turn mimetics {(2S,5S,11bR)- and (2R,5R,11bS)-2-amino
      5-carboxy-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole (IBTM) and
      beta-turn dipeptide, 2-oxo-7-thio-1-azabicyclo[4.3.0]nonane (BTD)}. The
      incorporation of the indolizinoindole IBTM type II beta-turn mimetic is preferred
      over its type II' counterpart for efficient CCK1 receptor recognition, while BTD
      derivatives were completely inactive. The structure-conformation-activity
      relationship study in the IBTM series has shown some essential requirement of
      these CCK4 derivatives to favorably interact with CCK1 receptors: (a) the
      adoption of turnlike conformations, (b) the presence of an L-Phe residue and a C
      terminal carboxamide moiety, and (c) the indole ring of the IBTM skeleton.
      Moreover, the existence of pi-pi interactions between the phenyl ring of d-Phe
      residues and the indole ring of IBTM framework is detrimental for binding
      affinity. A series of potent and selective CCK1 receptor antagonists, exemplified
      by compounds 8a and 8b, emerges among these IBTM-containing derivatives.

PMID- 16302808
TI  - Grafting aminocyclopentane carboxylic acids onto the RGD tripeptide sequence
      generates low nanomolar alphaVbeta3/alphaVbeta5 integrin dual binders.
AB  - Eleven gamma-aminocyclopentane carboxylic acid (Acpca) platforms, including four
      dihydroxy representatives (19-22), three hydroxy analogues (34-36), and four
      deoxy derivatives (30-33), were prepared in a chiral nonracemic format. These
      simple units were then grafted onto an Arg-Gly-Asp (RGD) tripeptide framework by
      a mixed solid phase/solution protocol delivering an ensemble of 11 macrocyclic
      analogues of type cyclo-[-Arg-Gly-Asp-Acpca-], 1-11. The individual compounds
      were evaluated for their binding affinity toward the alphaVbeta3 and alphaVbeta5
      integrin receptors. The analogue 10 exhibited a very interesting activity profile
      (IC50/alphaVbeta3= 1.5 nM; IC50/alphaVbeta5= 0.59 nM), comparable to that of
      reference compounds EMD121974 and ST1646. Closely related congeners 6, 8, and 9
      also proved to be excellent dual binders with activity levels in the low
      nanomolar range. The three-dimensional (3D) NMR solution structures were
      determined, and docking studies to X-ray crystal structure of the extracellular
      segment of integrin alphaVbeta3 in complex with the reference compound EMD121974
      were performed on selected analogues to elucidate the interplay between structure
      and function in these systems and to evidence the subtle bases for receptorial
      recognition. The results prove that the principle of isosteric dipeptide
      replacement for peptidomimetics design and synthesis can be violated, without
      detriment to the development of highly effective integrin binders.

PMID- 16302809
TI  - Interaction of papain-like cysteine proteases with dipeptide-derived nitriles.
AB  - A series of 44 dipeptide nitriles with various amino acids at the P2 position and
      glycine nitrile at position P1 were prepared and evaluated as inhibitors of
      cysteine proteinases. With respect to the important contribution of the P2-S2
      interaction to the formation of enzyme-inhibitor complexes, it was focused to
      introduce structural diversity into the P2 side chain. Nonproteinogenic amino
      acids were introduced, and systematic fluorine, bromine, and phenyl scans for
      phenylalanine in the P2 position were performed. Moreover, the N-terminal
      protection was varied. Kinetic investigations were carried out with cathepsin L,
      S, and K as well as papain. Changes in the backbone structure of the parent N
      (tert-butoxycarbonyl)-phenylalanyl-glycine-nitrile (16), such as the introduction
      of an R-configured amino acid or an azaamino acid into P2 as well as methylation
      of the P1 nitrogen, resulted in a drastic loss of affinity. Exemplarily, the
      cyano group of 16 was replaced by an aldehyde or methyl ketone function.
      Structure-activity relationships were discussed with respect to the substrate
      specificity of the target enzymes.

PMID- 16302810
TI  - Mono- or diphenylpyridazines connected to N-(2,4-difluorophenyl)-N'-heptylurea as
      acyl-CoA:cholesterol acyltransferase inhibitors.
AB  - Mono- and diphenylpyridazine ureido derivatives, structurally related to DuP 128,
      were synthesized and tested for their inhibitory activity against ACAT isolated
      from rat liver microsomes. Several compounds displayed ACAT inhibition in the
      micromolar range. The amino derivatives 4a-c were also tested against hACAT-1 and
      hACAT-2 isoforms. They retained the same trend shown in the previous assay.
      Modeling studies on representative terms were performed. Significant similarities
      between the geometrical features of the model DuP 128 and the most active
      pyridazine derivatives were observed.

PMID- 16302811
TI  - Binding of the anticancer prodrug CB1954 to the activating enzyme NQO2 revealed
      by the crystal structure of their complex.
AB  - CB1954 is an attractive prodrug for directed-enzyme prodrug therapy (DEPT) and a
      conventional prodrug against tumors in which the enzyme NQO2 is highly expressed.
      We have determined the crystal structure of the NQO2-CB1954 complex to 2.0 A
      resolution. The binding of the prodrug is governed by hydrophobic forces, while
      two key electrostatic contacts determine the specific orientation of the ligand.
      The structure also reveals an unfavorable interaction, therefore suggesting
      possible avenues for DEPT-tailored engineering studies.

PMID- 16302812
TI  - Syntheses, biological evaluation, and molecular modeling of 18F-labeled 4
      anilidopiperidines as mu-opioid receptor imaging agents.
AB  - The synthesis, evaluation, and molecular modeling of a series of 18F-labeled 4
      anilidopiperidines with high affinities for the mu-opioid receptor (mu-OR) are
      reported. On the basis of the high brain uptake and selective retention in brain
      regions that contain a high concentration of the mu-OR, combined with a good
      metabolic stability, [18F]fluoro-pentyl carfentanil ([18F]4) and 2-(+/
      )[18F]fluoropropyl-sufentanil ([18F]6) were selected as the lead compounds for
      further evaluation. The binding affinity to the human mu-OR was 0.74 and 0.13 nM
      for [18F]4 and [18F]6, respectively. In vitro autoradiography of [18F]4 and
      [18F]6 on rat brain sections produced patterns in accordance with the known
      distribution of mu-OR expression. Structure-activity relationships of the
      fluorinated compounds are discussed with respect to the interaction with an
      activated-state model of the mu-OR. Taken together, the in vivo and in vitro data
      indicate that [18F]4 and [18F]6 hold promise for studying the mu-opioid receptor
      in humans by means of positron emission tomography.

PMID- 16302813
TI  - Novel lavendamycin analogues as antitumor agents: synthesis, in vitro
      cytotoxicity, structure-metabolism, and computational molecular modeling studies
      with NAD(P)H:quinone oxidoreductase 1.
AB  - Novel lavendamycin analogues with various substituents were synthesized and
      evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor
      agents. Pictet-Spengler condensation of quinoline- or quninoline-5,8-dione
      aldehydes with tryptamine or tryptophans yielded the lavendamycins. Metabolism
      studies with recombinant human NQO1 revealed that addition of NH2 and CH2OH
      groups at the quinolinedione-7-position and indolopyridine-2'-position had the
      greatest positive impact on substrate specificity. The best and poorest
      substrates were 37 (2'-CH2OH-7-NH2 derivative) and 31 (2'-CONH2-7-NHCOC3H7-n
      derivative) with reduction rates of 263 +/- 30 and 0.1 +/- 0.1 micromol/min/mg
      NQO1, respectively. Cytotoxicity toward human colon adenocarcinoma cells was
      determined for the lavendamycins. The best substrates for NQO1 were also the most
      selectively toxic to the NQO1-rich BE-NQ cells compared to NQO1-deficient BE-WT
      cells with 37 as the most selective. Molecular docking supported a model in which
      the best substrates were capable of efficient hydrogen-bonding interactions with
      key residues of the active site along with hydride ion reception.

PMID- 16302814
TI  - Structure-activity relationships in 1,4-benzodioxan-related compounds. 8.(1) {2
      [2-(4-chlorobenzyloxy)phenoxy]ethyl}-[2-(2,6-dimethoxyphenoxy)ethyl]amine
      (clopenphendioxan) as a tool to highlight the involvement of alpha1D- and alpha1B
      adrenoreceptor subtypes in the regulation of human PC-3 prostate cancer cell
      apoptosis and proliferation.
AB  - A series of new alpha1-adrenoreceptor antagonists (5-18) was prepared by
      introducing various substituents (Topliss approach) into the ortho, meta, and
      para positions of the benzyloxy function of the phendioxan open analogue 4
      ("openphendioxan"). All the compounds synthesized were potent antagonists and
      generally displayed, similarly to 4, the highest affinity values at alpha1D- with
      respect to alpha1A- and alpha1B-AR subtypes and 5-HT1A subtype. By sulforhodamine
      B (SRB) assay on human PC-3 prostate cancer cells, the new compounds showed
      antitumor activity (estimated on the basis of three parameters GI50, TGI, LC50),
      at low micromolar concentration, with 7 ("clopenphendioxan") exhibiting the
      highest efficacy. Moreover, this study highlighted for the first time alpha1D-
      and alpha1B-AR expression in PC3 cells and also demonstrated the involvement of
      these subtypes in the modulation of apoptosis and cell proliferation. A
      significant reduction of alpha1D- and alpha1B-AR expression in PC3 cells was
      associated with the apoptosis induced by 7. This depletion was completely
      reversed by norepinephrine.

PMID- 16302815
TI  - Docking studies and ligand recognition in folylpolyglutamate synthetase.
AB  - Folylpolyglutamate synthetase (FPGS) catalyzes the sequential addition of several
      glutamates to folate, forming gamma-linked polyglutamate folates of varying
      lengths. To understand how this protein is capable of accommodating ligands of
      different length and net charge, we have performed docking studies for folate
      substrates and glutamate based on the ternary crystal structure of Lactobacillus
      casei FPGS. Our results suggest two locations for folate binding, the one seen in
      the crystal structure and another distinct cavity. According to our model and
      experimental data, it is highly probable that folate can bind in both sites, and
      we suggest that the new pocket is especially important for the initial addition
      of the first glutamate residue. Docking longer substrates, di- and
      triglutamylated folates, showed how these molecules bind in the same sites. The
      longer folates also adopted transition-state-like conformations that may help us
      to understand the ligation reaction in FPGS and influence the design of mechanism
      based inhibitors for anticancer or antimicrobial therapy.

PMID- 16302816
TI  - Conformationally sampled pharmacophore for peptidic delta opioid ligands.
AB  - Opioids represent the frontline treatment for acute pain, despite their side
      effects, motivating efforts toward developing novel opioid analgesics. To
      facilitate these efforts, a novel modeling approach, the conformationally sampled
      pharmacophore (CSP), has been developed that increases the probability of
      including the receptor bound form in the model. This method, originally used for
      developing a nonpeptidic delta opioid efficacy pharmacophore, is extended to
      peptidic ligands using replica exchange molecular dynamics simulation for
      conformational sampling. The developed 2D CSP indicates that the spatial
      relationship of the basic nitrogen and the hydrophobic moiety in the delta opioid
      ligands differentiates activity. In addition, results indicate that both peptidic
      and nonpeptidic ligands have the same binding mode with the receptor. Thus, the
      CSP approach distinguishes both peptidic and nonpeptidic delta opioid agonists
      and antagonists and is anticipated to be of general utility for the development
      of pharmacophores for species with multiple rotatable bonds.

PMID- 16302817
TI  - Small molecule inhibitors of dynamin I GTPase activity: development of dimeric
      tyrphostins.
AB  - Dynamin I is a GTPase enzyme required for endocytosis and is an excellent target
      for the design of potential endocytosis inhibitors. Screening of a library of
      tyrphostins, in our laboratory, against the GTPase activity of dynamin I gave
      rise to a microM potent lead, 2-cyano-3-(3,4-dihydroxyphenyl)thioacrylamide (1,
      IC50 70 microM). Our initial investigations suggested that only the dimeric form
      of 1 displayed dynamin I GTPase inhibitory activity. Subsequent synthetic
      iterations were based on dimeric analogues and afforded a number of small
      molecules, low microM potent, inhibitors of dynamin I GTPase, in particular,
      symmetrical analogues with a minimum of two free phenolic -OHs: catechol
      acrylamide (9) (IC50= 5.1 +/- 0.6 microM), its 3,4,5-trihydroxy congener (10)
      (IC50= 1.7 +/- 0.2 microM), and the corresponding 3-methyl ether (11) (IC50= 9 +/
      3 microM). Increasing the length of the central alkyl spacer from ethyl to
      propyl (22-24) afforded essentially identical activity with IC50's of 1.7 +/-
      0.2, 1.7 +/- 0.2, and 5 +/- 1 microM, respectively. No decrease in activity was
      noted until the introduction of a hexyl spacer. Our studies highlight the
      requirement for two free amido NHs with neither the mono-N-methyl (86) nor the
      bis-N-methyl (87) analogues inhibiting dynamin I GTPase. A similar effect was
      noted for the removal of the nitrile moieties. However, modest potency was
      observed with the corresponding ester analogues of 9-11: ethyl ester (90), propyl
      ester (91), and butyl ester (92), with IC50's of 42 +/- 3, 38 +/- 2, and 61 +/- 2
      microM, respectively. Our studies reveal the most potent and promising dynamin I
      GTPase inhibitor in this series as (22), which is also known as BisT.

PMID- 16302818
TI  - Design, synthesis, and biological evaluation of sirtinol analogues as class III
      histone/protein deacetylase (Sirtuin) inhibitors.
AB  - In a search for potent inhibitors of class III histone/protein deacetylases
      (sirtuins), a series of sirtinol analogues have been synthesized and the degree
      of inhibition was assessed in vitro using recombinant yeast Sir2, human SIRT1,
      and human SIRT2 and in vivo with a yeast phenotypic assay. Two analogues, namely,
      3- and 4-[(2-hydroxy-1-naphthalenylmethylene)amino]-N-(1-phenylethyl)benzamide
      (i.e., m- and p-sirtinol), were 2- to 10-fold more potent than sirtinol against
      human SIRT1 and SIRT2 enzymes. In yeast in vivo assay, these two small molecules
      were as potent as sirtinol. Compounds lacking the 2-hydroxy group at the
      naphthalene moiety or bearing several modifications at the benzene 2'-position of
      the aniline portion (carbethoxy, carboxy, and cyano) were 1.3-13 times less
      potent than sirtinol, whereas the 2'-carboxamido analogue was totally inactive.
      Both (R)- and (S)-sirtinol had similar inhibitory effects on the yeast and human
      enzymes, demonstrating no enantioselective inhibitory effect.

PMID- 16302819
TI  - Evaluating the molecular mechanics poisson-boltzmann surface area free energy
      method using a congeneric series of ligands to p38 MAP kinase.
AB  - The recently described molecular mechanics Poisson-Boltzmann surface area (MM
      PBSA) method for calculating free energies is applied to a congeneric series of
      16 ligands to p38 MAP kinase whose binding constants span approximately 2 orders
      of magnitude. These compounds have previously been used to test and compare other
      free energy calculation methods, including thermodynamic integration (TI), OWFEG,
      ChemScore, PLPScore, and Dock Energy Score. We find that the MM-PBSA performs
      relatively poorly for this set of ligands, yielding results much inferior to
      those from TI or OWFEG, inferior to Dock Energy Score, and not appreciably better
      than ChemScore or PLPScore but at an appreciably larger computational cost than
      any of these other methods. This suggests that one should be selective in
      applying the MM-PBSA method and that for systems that are amenable to other free
      energy approaches, these other approaches may be preferred. We also examine the
      single simulation approximation for MM-PBSA, whereby the required ligand and
      protein trajectories are extracted from a single MD simulation rather than two
      separate MD runs. This assumption, sometimes used to speed the MM-PBSA
      calculation, is found to yield significantly inferior results with only a
      moderate net percentage reduction in total simulation time.

PMID- 16302820
TI  - Adenosine kinase inhibitors. 6. Synthesis, water solubility, and antinociceptive
      activity of 5-phenyl-7-(5-deoxy-beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidines
      substituted at C4 with glycinamides and related compounds.
AB  - 4-(Phenylamino)-5-phenyl-7-(5-deoxy-beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine
      1 and related compounds known as "diaryltubercidin" analogues are potent
      inhibitors of adenosine kinase (AK) and are orally active in animal models of
      pain such as the rat formalin paw model (GP3269 ED50= 6.4 mg/kg). However, the
      utility of this compound class is limited by poor water solubility that can be
      attributed to the high energy of crystallization caused by stacking of the
      parallel C4 and C5 aryl rings in the solid state (compound 1 and GP3269 each with
      pH 7.4 solubility <0.05 microg/mL). To increase water solubility, the hydrophobic
      C4-phenylamino substituent was replaced with a more hydrophilic group,
      glycinamide. This modification resulted in improved water solubility while
      retaining AK inhibition potency. Analogues were studied where changes in the
      glycinamide moiety were combined with changes to the base and sugar. A lead
      compound, 4-N-(N-cyclopropylcarbamoylmethyl)amino-5-phenyl-7-(5-deoxy-beta-D
      ribofuranosyl)pyrrolo[2,3-d]pyrimidine (16c) (IC50= 3 nM and water solubility =
      32 +/- 9 microg/mL at pH 7.4), was further characterized in biological assays.
      Compound 16c exhibited strong oral efficacy in the rat formalin paw model (ED50
      of 2.5 mg/kg). In the most advanced assay, 16c was found to inhibit bradykinin
      induced licking in marmoset monkeys with an ED50 estimated at 0.9 mg/kg without
      producing evidence of side effects such as ataxia, sedation, and emesis at this
      dose. However, lethal toxicity in the rat formalin paw model occurred with high
      doses of 16c, and further work on this series was discontinued.

PMID- 16302821
TI  - Platinum-based antitumor drugs containing enantiomerically pure alpha
      trifluoromethyl alanine as ligand.
AB  - Synthetic amino acids such as fluorinated alpha-amino acids are currently
      actively investigated for their biological activity. Herein, we report on the
      synthesis and characterization of platinum complexes containing an N,O-chelated
      pure enantiomer of alpha-trifluoromethylalanine (alpha-Tfm-Ala). The compounds
      are either anionic, K[PtCl2(alpha-Tfm-Ala)], or cationic, [PtAm2(alpha-Tfm
      Ala)](NO3) (Am2= (NH3)2, ethylendiamine (en), 1,10-phenanthroline (phen), and 2,9
      dimethyl-1,10-phenanthroline (Me2phen)). All complexes are highly soluble in
      water and have been fully characterized by NMR spectroscopy. In vitro
      cytotoxicity assays on different human tumor cell lines have been performed on
      some of the isolated compounds. [Pt(NH3)2(alpha-Tfm-Ala)] with R configuration of
      the amino acid proved to have an activity comparable to that of the reference
      compound cisplatin. Flow cytometric analysis on NCI-H460 tumor cells (absence of
      G2/M arrest, which instead is observed in the case of cisplatin) suggests a
      mechanism of action different from that of cisplatin.

PMID- 16302822
TI  - Discovery of potent chromen-4-one inhibitors of the DNA-dependent protein kinase
      (DNA-PK) using a small-molecule library approach.
AB  - Structure-activity relationships for inhibition of DNA-dependent protein kinase
      (DNA-PK) have been defined for substituted chromen-4-ones. For the 2-amino
      substituted benzo[h]chromen-4-ones, a morpholine substituent at this position was
      essential for activity. Small libraries of 6- and 7-alkoxy-substituted chromen-4
      ones showed that a number of 7-alkoxy-substituted chromenones displayed improved
      activity. Focused libraries incorporating 6-, 7-, and 8-aryl and heteroaryl
      substituents were prepared. In these cases, 6- and 7-substitution was disfavored,
      whereas 8-substitution was largely tolerated. Surprisingly, two compounds, 2-N
      morpholino-8-dibenzofuranyl-chromen-4-one (NU7427, 32{38}) and the 2-N-morpholino
      8-dibenzothiophenyl-chromen-4-one (NU7441, 32{26}) were excellent inhibitors
      (IC50 vs DNA-PK = 40 and 13 nM, respectively). The ring-saturated analogue 2-N
      morpholino-8-(6',7',8',9'-tetrahydrodibenzothiophene)chromen-4-one, 36, retained
      potent activity (IC50 vs DNA-PK = 23 nM). The dibenzothiophene 32{38} sensitized
      HeLa cells to ionizing radiation in vitro, with dose modification factors of 2.5
      at 10% survival being observed at 0.5 microM. The cytotoxicity of the
      topoisomerase II inhibitor etoposide was also potentiated.

PMID- 16302823
TI  - On the use of nonfluorescent dye labeled ligands in FRET-based receptor binding
      studies.
AB  - The efficiency of fluorescence resonance energy transfer (FRET) is dependent upon
      donor-acceptor proximity and spectral overlap, whether the acceptor partner is
      fluorescent or not. We report here on the design, synthesis, and characterization
      of two novel pirenzepine derivatives that were coupled to patent blue VF and
      pinacyanol dyes. These nonfluorescent compounds, when added to cells stably
      expressing enhanced green fluorescent protein (EGFP)-fused muscarinic M1
      receptors, promote EGFP fluorescence extinction in a time-, concentration-, and
      atropine-dependent manner. They display nanomolar affinity for the muscarinic
      receptor, determined using either FRET or classical radioligand binding
      conditions. We provide evidence that these compounds behave as potent acceptors
      of energy from excited EGFP with quenching efficiencies comparable to those of
      analogous fluorescent bodipy or rhodamine red pirenzepine derivatives. The
      advantages they offer over fluorescent ligands are illustrated and discussed in
      terms of reliability, sensitivity, and wider applicability of FRET-based receptor
      binding assays.

PMID- 16302824
TI  - Carbonic anhydrase inhibitors. The mitochondrial isozyme VB as a new target for
      sulfonamide and sulfamate inhibitors.
AB  - A lately discovered carbonic anhydrase (hCA, EC 4.2.1.1), the mitochondrial hCA
      VB, was cloned, expressed, and purified. Kinetic parameters proved it to be 3.37
      times more effective than hCA VA as a catalyst for the physiological reaction,
      with kcat = 9.5 x 10(5) s(-1) and kcat/K(M) = 9.8 x 10(7) M(-1) s(-1), being
      second only to hCA II among the 16 isoforms presently known in humans. We
      investigated the inhibition of hCA VB with a library of sulfonamides/sulfamates,
      some of which are clinically used compounds. Benzenesulfonamides were ineffective
      inhibitors, whereas derivatives bearing 4-amino, 4-hydrazino, 4-methyl, 4-carboxy
      moieties or halogenated sulfanilamides were more effective (Ki's of 1.56-4.3
      microM). Among the 10 clinically used compounds, acetazolamide, benzolamide,
      topiramate, and indisulam showed effective inhibitory activity (Ki's of 18-62
      nM). Three compounds showed better activity against hCA VB over hCA II, among
      which were sulpiride and ethoxzolamide, which were 2 times more effective
      inhibitors of the mitochondrial over the cytosolic isozyme. hCA VB is a druggable
      target and some of its inhibitors may lead to the development of novel
      antiobesity therapies.

PMID- 16302825
TI  - Synthesis and pharmacology of willardiine derivatives acting as antagonists of
      kainate receptors.
AB  - The natural product willardiine (8) is an AMPA receptor agonist while 5
      iodowillardiine (10) is a selective kainate receptor agonist. In an attempt to
      produce antagonists of kainate and AMPA receptors analogues of willardiine with
      substituents at the N3 position of the uracil ring were synthesized. The N3-4
      carboxybenzyl substituted analogue (38c) was found to be equipotent at AMPA and
      GLUK5-containing kainate receptors in the neonatal rat spinal cord. The N3-2
      carboxybenzyl substituted analogue (38a) proved to be a potent and selective
      GLUK5 subunit containing kainate receptor antagonist when tested on native rat
      and human recombinant AMPA and kainate receptor subtypes. The GLUK5 kainate
      receptor antagonist activity was found to reside in the S enantiomer (44a)
      whereas the R enantiomer (44b) was almost inactive. 5-Iodo substitution of the
      uracil ring of 44a gave 45, which was found to have enhanced potency and
      selectivity for GLUK5.

PMID- 16302826
TI  - Discovery and development of a new class of potent, selective, orally active
      oxytocin receptor antagonists.
AB  - We report a novel chemical class of potent oxytocin receptor antagonists showing
      a high degree of selectivity against the closely related vasopressin receptors
      (V1a, V1b, V2). An initial compound, 7, was shown to be active in an animal model
      of preterm labor when administered by the intravenous but not by the oral route.
      Stepwise SAR investigations around the different structural elements revealed one
      position, the arenesulfonyl moiety, to be amenable to structural changes.
      Consequently, this position was used to introduce a variety of substituents to
      improve the physicochemical properties. Some of the resulting analogues were
      found to be superior to 7 both in terms of potency in vitro and aqueous
      solubility, which translated into significantly improved efficacy in the animal
      model after intravenous and oral administration. The best compound, 73, potently
      inhibited oxytocin-induced uterine contractions in nonpregnant rats and reduced
      spontaneous uterine contractions in late-term pregnant rats.

PMID- 16302827
TI  - Design, synthesis, and biological evaluation of hybrid molecules containing alpha
      methylene-gamma-butyrolactones and alpha-bromoacryloyl moieties.
AB  - The synthesis and biological activity of hybrids 8-18 prepared combining alpha
      methylene-gamma-butyrolactones and alpha-bromoacryloylamides have been described
      and their structure-activity relationships discussed. All these
      heterobifunctional compounds demonstrate good antileukemic activity,
      significantly superior to that of both alkylating units alone. Using the human
      leukemia HL-60 cell line, selected compounds 10, 11, 13, and 17 were found to
      induce morphological changes and internucleosomal DNA fragmentation
      characteristic of apoptotic cell death.

PMID- 16302828
TI  - Structure of a synthetic fragment of the lipopolysaccharide (LPS) binding protein
      when bound to LPS and design of a peptidic LPS inhibitor.
AB  - Peptidic lipopolysaccharide (LPS) antagonists are the subject of intensive
      research. We report an NMR and modeling study of LBP-14 (RVQGRWKVRASFFK), a
      synthetic fragment of the LPS binding protein (LBP). In a mixture with LPS we
      observed the transferred nuclear Overhauser effect and determined the LPS-bound
      structure of LBP-14 that was used for docking calculations to LPS. The derived
      complex was used to design a peptide that displayed more than 50% increase in LPS
      inhibition in vitro.

PMID- 16302830
TI  - Disasters and children.

PMID- 16302831
TI  - Racial/ethnic disparities in child health: familiar problems and unknown
      solutions.

PMID- 16302832
TI  - Disparities for latino children in the timely receipt of medical care.
AB  - OBJECTIVE: It is not known whether Latino children, the largest minority
      population in the United States, experience disparities in the timeliness of
      their access to health care. We compared timeliness of care among Latino, white,
      and African American children. METHODS:  DESIGN: cross-sectional cohort from the
      2000 Medical Expenditure Panel Survey. PATIENTS: children with a usual source of
      care. OUTCOME MEASURE: timeliness of care was assessed using parent reports of
      their child's 1) routine care, 2) illness care, 3) phone help, and 4)
      experiencing of a brief wait time. ANALYSIS: multiple logistic regression was
      used to determine the adjusted odds of not always receiving timely medical care.
      RESULTS: Four-thousand one-hundred twenty children were included. Latino children
      were less likely to always (P < .05) receive timely care compared with whites and
      African Americans, respectively, in 3 areas: routine care, phone help, and brief
      wait time. Multiple regression revealed decreased relative risks (RR, 95% CI) of
      always receiving timely medical care for Latinos in the same areas: routine care,
      compared with whites (0.88, 0.79-0.98) and African Americans (0.81, 0.70-0.93);
      phone help, compared with whites (0.84, 0.76-0.92) and African Americans (0.86,
      0.76-0.960); and brief wait time, compared with whites (0.71, 0.65-0.80) and
      African Americans (0.81, 0.70-0.92). With parental survey language in the model,
      Latinos experienced decreased timeliness of care for routine care compared with
      African Americans (0.85, 0.72-0.98); phone help compared with whites (0.87, 0.77
      0.96); and brief wait times compared with whites (0.79, 0.71-0.87). CONCLUSIONS:
      Latino children experience marked disparities in obtaining timely medical care,
      only some of which is associated with language differences.

PMID- 16302833
TI  - Characteristics of families that complain following pediatric emergency visits.
AB  - OBJECTIVE: The voicing of unsolicited observations by patients and families is a
      form of participation in the health care system. We investigated whether visits
      by patients of different race/ethnicities were equally represented in unsolicited
      complaints filed with a medical center's Office of Patient Affairs (OPA)
      regarding pediatric emergency visits. METHODS: We conducted a population-based
      retrospective study, including pediatric emergency visits, at a large academic
      medical center between January 1999 and December 2002. We identified complaints
      to the OPA and conducted bivariate and multivariable analyses to determine
      whether patient race/ethnicity was associated with filing a complaint. RESULTS:
      Among 105 322 total visits, the overall complaint rate was 1.22/1000 visits.
      Visits by white children had a complaint rate of 1.78/1000 visits compared with
      0.37/1000 visits by African American children (P < .001). In multivariable
      analysis, visits by African American children remained less likely to be
      associated with a complaint to the OPA compared with visits by white children
      (adjusted odds ratio 0.30, 95% CI 0.17-0.55) after controlling for factors such
      as payer status. CONCLUSIONS: Emergency-department visits by African American
      children were less likely to be associated with a complaint than visits by white
      children. Programs that use complaints in service recovery, quality assurance,
      and risk management efforts may unintentionally exclude segments of the patient
      population served by the institution.

PMID- 16302834
TI  - How Medicaid and the State Children's Health Insurance Program can do a better
      job of insuring uninsured children: the perspectives of parents of uninsured
      Latino children.
AB  - BACKGROUND: Eight and a half million US children are uninsured, despite the 1997
      enactment of the State Children's Health Insurance Program (SCHIP) with $39
      billion in funding, and Latinos continue to be the most uninsured racial/ ethnic
      group, with 24% (3 million) uninsured. Why SCHIP and Medicaid have not been more
      successful insuring uninsured children is unclear. OBJECTIVE: To identify reasons
      why parents are unable to insure uninsured Latino children in a state where all
      low-income children are eligible for insurance. METHODS: Bilingual focus groups
      of parents of uninsured Latino children from Boston communities with the highest
      proportion of uninsured Latino children. RESULTS: The 30 parents interviewed in 6
      focus groups had a mean age of 39 years; 63% never graduated high school and 33%
      were US citizens. The mean age of their children was 12 years, and the median
      annual family income was $9120. Parents reported 52 barriers to insuring
      children. Major obstacles included lack of knowledge about the application
      process and eligibility (especially misconceptions about work, welfare, and
      immigration), language barriers, immigration issues, income, hassles, pending
      decisions, family mobility, misinformation from insurance representatives (being
      told insurance is too expensive and parents must work), and system problems
      (including lost applications, discrimination, and excessive waits). Parents
      universally agreed case managers would be helpful in insuring uninsured children.
      CONCLUSIONS: Even in a state where all low-income children are eligible for
      health insurance, current SCHIP and Medicaid outreach and enrollment are not
      effectively reaching uninsured Latino children. Parents need better information
      about programs, eligibility, and the application process, and a more efficient,
      user-friendly system.

PMID- 16302835
TI  - The co-occurrence of maternal depressive symptoms and smoking in a national
      survey of mothers.
AB  - CONTEXT: Both maternal smoking and depression are common and can adversely impact
      child health and functioning, yet few studies have explored their co-occurrence
      among mothers. OBJECTIVE: To determine the prevalence and associations of
      depression and smoking among mothers in the United States. DESIGN: Random-digit
      dial national telephone survey of 1530 households conducted in 2002. Respondents
      were asked about their sociodemographic characteristics, smoking status, and
      their children's receipt of Medicaid. A validated 3-item depression screen was
      administered. Bivariate and multiple regression analyses for maternal smoking and
      a positive depression screen were performed. SETTING: National sample.
      PARTICIPANTS: Seven hundred two mothers with children aged less than 19 years
      living in their homes. RESULTS: The response rate was 61%. Among mothers, 24.3%
      were smokers, 24.4% had a positive depression screen, 8.1% had both, and 40.6%
      were smokers and/or had a positive depression screen. All rates were greater
      among mothers whose children receive Medicaid (37.6%, 47.5%, 20.6%, and 64.5%)
      than those whose children do not receive Medicaid (21.1%, 19.0%, 4.8%, and 35.3%)
      (P < .001) for each. In multivariate analyses, maternal smoking was independently
      associated with a 70% increased risk of depressive symptoms (odds radio, 1.7; 95%
      confidence interval, 1.1-2.6). CONCLUSIONS: This study highlights both the
      frequency and the co-occurrence of maternal smoking and maternal depressive
      symptoms, two negative influences on children's health and development, as well
      as their increased prevalence among mothers whose children receive Medicaid,
      thereby highlighting the economic disparities associated with both. These
      findings have significant implications for our nation's children, health care
      clinicians, and health care payers.

PMID- 16302837
TI  - Breast-feeding history and overweight in Latino preschoolers.
AB  - OBJECTIVE: Describe the relationship between breast-feeding history and risk of
      overweight in the preschool years in a sample of primarily Mexican-origin
      Latinos. METHODS: Children's breast-feeding history, health history, and
      demographics were obtained in interviewer-administered questionnaires of a
      convenience sample of 364 parents of children ages 2-5 in an outpatient clinic
      waiting room serving a predominantly Mexican immigrant population in a large
      Midwestern city. Child weight status was determined by weighing and measuring
      each child and calculating age- and sex-specific body mass index (BMI) percentile
      using 2000 Centers for Disease Control reference values, with children > or =95th
      percentile defined as overweight. RESULTS: Seventy-six of 364 children (21%) were
      overweight. Eighty-seven percent of children had been breast-fed. Increased
      duration of breast-feeding was associated with a linearly decreased risk of
      overweight in bivariate analysis, ranging from an overweight prevalence of 35%
      for those never breast-fed to 12% for those breast-fed for at least a year. This
      inverse relationship remained significant in the smaller sample for which
      maternal BMI data were available (n = 127), as each additional month of breast
      feeding was associated with a 10% decreased odds ratio (OR) of overweight
      (adjusted OR = 0.90; 95% CI = 0.81, 0.99) after controlling for child's sex,
      current age, prematurity, birth-weight category, maternal education level, and
      maternal weight status. CONCLUSION: This sample of children of Mexican-origin
      immigrant families had high rates of overweight at very young ages but also very
      high rates of breast-feeding. Duration of breast-feeding was strongly and
      inversely related with prevalence of overweight as a preschooler.

PMID- 16302836
TI  - Barriers to following the back-to-sleep recommendations: insights from focus
      groups with inner-city caregivers.
AB  - BACKGROUND: African American infants have a higher incidence of SIDS and
      increased risk of being placed in the prone position for sleep. OBJECTIVE: To
      determine new barriers and more information about previously identified barriers
      that interfere with adherence to the Back-to-Sleep recommendations among inner
      city, primarily African Americans. DESIGN/METHODS: We conducted 9 focus groups
      with caregivers of infants and young children from women, infants, and children
      centers and clinics in New Haven and Boston. Themes were identified using
      standard qualitative techniques. RESULTS: Forty-nine caregivers participated, of
      whom 86% were African American, 6% were Hispanic, 4% were white, and 4% were
      other. Four themes were identified: 1) SAFETY: Participants chose the position
      for their infants based on which position they believed to be the safest. Some
      participants did not choose to put their infants in the supine position for sleep
      because they feared their infants would choke; 2) Advice: Participants relied on
      the advice of more experienced female family members. Health care providers were
      not uniformly a trusted source of advice; 3) Comfort: Participants made choices
      about their infants sleeping positions based on their perceptions of whether the
      infants appeared comfortable. Participants thought that their infants appeared
      more comfortable in the prone position; 4) Knowledge: Some participants had
      either limited or erroneous knowledge about the Back-to-Sleep recommendations.
      CONCLUSIONS: We identified multiple barriers to adherence to recommendations
      regarding infant sleep position. Data obtained from these focus groups could be
      used to design educational interventions aimed at improving communication about
      and adherence to the Back-to-Sleep recommendations.

PMID- 16302838
TI  - Analgesic effects of breast-feeding or pacifier use with maternal holding in term
      infants.
AB  - OBJECTIVES: First, to compare analgesic effects of breast-feeding versus pacifier
      use in newborn infants undergoing blood collection via heel sticks. Second, to
      compare analgesic effects of pacifier use with maternal holding versus
      nonmaternal holding. DESIGN: A prospective, randomized, controlled trial.
      SETTING: Normal newborn nursery at academic teaching hospital. PARTICIPANTS: Full
      term breast-feeding infants scheduled for routine newborn screening blood test
      via heel stick (n = 96). Interventions.-Infants randomized to 3 groups for
      analgesia: 1) breast-feeding, 2) pacifier use while held by mothers, 3) pacifier
      use while held by research assistants (nonmothers). OUTCOME MEASURES: Primary
      outcome was crying (percent of infants who cried during the procedure and mean
      percent of procedure time that infants cried). Secondary outcomes were
      physiologic measures. RESULTS: Fewer breast-feeding infants cried than infants
      using a pacifier while held by nonmothers both during the procedure (69% vs 100%,
      P < .01) and after the procedure (28% vs 60%, P = .03). Those infants crying
      during the procedure cried for less time if held by their mothers either breast
      feeding (33%, P < .01) or using a pacifier (45%, P = .03) than those using a
      pacifier while being held by nonmothers (66%). CONCLUSION: Breast-feeding is more
      analgesic than pacifier use with nonmaternal holding. Maternal holding with
      either breast-feeding or pacifier use is more analgesic than nonmaternal holding
      with pacifier use, suggesting that maternal holding itself has an analgesic
      effect. Breast-feeding and maternal holding should be considered as pain-control
      measures for the neonate during heel-stick procedures.

PMID- 16302839
TI  - Knowledge and beliefs about guidelines for exclusion of ill children from child
      care.
AB  - BACKGROUND: The American Academy of Pediatrics published national child care
      illness exclusion guidelines in 1992 and 2002. To our knowledge, no published
      studies have examined child care providers', parents', and pediatricians'
      knowledge or beliefs about these guidelines. OBJECTIVE: To compare parents',
      pediatricians', and center-based child care providers' (CCPs) knowledge and
      beliefs about exclusion guidelines. DESIGN: Cross-sectional survey conducted in
      2000 of 80 CCPs, 142 parents, and 36 pediatricians in Baltimore City. Main
      outcome measures included familiarity with and knowledge of exclusion guidelines
      and beliefs about exclusion effectiveness among these groups. RESULTS: Response
      rates were 58% for parents, 59% for pediatricians, 85% for CCPs. Sixteen percent
      of child care providers (CCPs), 39% of parents, and 53% of pediatricians had not
      seen any written exclusion guidelines. Compared with national guidelines for 12
      common symptoms, responses from CCPs and parents indicated overexclusion, while
      pediatricians indicated underexclusion. The groups scored similarly in number of
      correct answers on knowledge items (CCPs 63%, parents 64%, pediatricians 61%, P =
      .44). More CCPs and parents than pediatricians believed that exclusion
      effectively controlled infection spread and that sick children should be excluded
      because they spread disease, would be more comfortable, and recover faster at
      home (P < .001). CONCLUSIONS: This survey found CCPs, parents, and pediatricians
      all failed to recognize how national guidelines recommended managing 4 out of 10
      common conditions on average. CCPs were more likely than pediatricians to believe
      that exclusion was warranted to control infection or for the child's personal
      needs.

PMID- 16302840
TI  - Anticipatory guidance topics: are more better?
AB  - OBJECTIVE: Anticipatory guidance is a cornerstone of primary care pediatrics.
      Despite the fact that retention of information is essential for later action,
      data are lacking on what parents recall immediately after the visit and 1 month
      later and how the total number of topics discussed affects this outcome. METHODS:
      Parents and practitioners completed postvisit surveys of anticipatory guidance
      topics discussed during health-maintenance visits for children ages 2-11.
      Postvisit and 1 month later, parental recall was compared with provider report of
      topics discussed. We examined the relationship between parental recall and the
      total number of topics discussed. RESULTS: Families with children ages 2-11 years
      from across the United States participated in this study (N = 861). Providers
      reported discussing the topics of nutrition, car restraints, dental care, and
      reading aloud most often (72%- 93%). Concordance between parent and provider was
      high for all topics (72%-90%). Immediately postvisit, parents reported 6.33 (SD
      2.9) as the mean number of topics discussed while providers reported 6.9 (SD 2.7)
      as the mean number of topics discussed. However, parental recall decreased
      significantly with more topics (> or =9) discussed. The same trend existed 1
      month later. CONCLUSIONS: Providers and parents have good agreement about topics
      discussed or not discussed during a well-child visit; however, parental recall
      dwindles with increasing numbers of topics discussed. Rethinking well-child care
      to limit the total number of topics discussed is warranted.

PMID- 16302841
TI  - Pediatric obesity-related counseling in the outpatient setting.
AB  - OBJECTIVE: To determine rates of pediatric obesity-related counseling in the
      outpatient setting. METHODOLOGY: The 1993-2002 data from the National Ambulatory
      Medical Care Survey (NAMCS) and the National Hospital Ambulatory Care Survey
      (NHAMCS) were extracted for estimates of 1) percentage of all pediatric
      encounters that included obesity-related counseling and 2) percentage of all
      pediatric encounters that included general growth/ development counseling.
      Obesity-related counseling rates were compared with corresponding
      growth/development counseling rates and with the number of pediatric-obesity
      articles listed in Medline for each year. RESULTS: The rate of obesity-related
      counseling steadily improved and was correlated with the number of published
      obesity articles (Spearman's rho .721) between 1993 and 2002. In 1995, for
      example, 4.3% of encounters included such counseling, compared with 19.0% in 2001
      and 15.4% in 2002. CONCLUSIONS: Obesity-related counseling has become an
      important part of ambulatory care, which suggests increasing awareness of this
      serious problem.

PMID- 16302842
TI  - Luminescence quenching of Eu(III) carboxylates by Cu(II) in a composite polymer
      xerogel film.
AB  - Three Eu(III) luminescent compounds were separately entrapped in a xerogel porous
      silica matrix and finely ground particles of it were deposited on a glass support
      with polyvinylacetate (PVAc) as a binder to build a thin film sensor. These 3
      devices were immersed in aqueous solutions of Cu(II) and the content of this
      metal was evaluated by emission-quenching experiments. The sensor containing the
      highly luminescent antenna chelate of diethylenetriaminepentaacetic acid (dtpa)
      sensitized with Coumarin120 rendered the largest Stern-Volmer constant (K(SV) =
      1.49 x 10(4) M(-1)), showing no leaching of the Eu(III) complex to the aqueous
      solution and a reproducible value of the luminescence ratio between water and
      Cu(II) solution. The in situ sensor we developed can measure the concentration of
      Cu(II) in aqueous media down to the ppm level by emission-quenching experiments.
      This methodology permits a simple calibration of the sensor and an easy to use
      reusable device.

PMID- 16302843
TI  - Public health challenges in Kyrgyzstan: developing a new curriculum.
AB  - INTRODUCTION: The public health challenges facing the Central Asian Republic of
      Kyrgyzstan are rooted in the social, economic and political conditions that
      emerged after the collapse of the Soviet Union in 1991. Geographically remote and
      with a substantial part of it's population living in mountainous rural villages,
      economic recovery and the maintenance of basic standards of public health is now
      a major problem for the Kyrgyz people. This project report sets out the case for
      restructuring public health education in Kyrgyzstan. It also explains how a new
      public health curriculum will equip Kyrgyz students with the knowledge and skills
      to work effectively with urban and rural communities in this geographically
      remote region of Central Asia. METHODS: With financial support from the European
      Union's Tempus program St Martin's College, the Kyrgyz State Medical Academy
      (KSMA) and Pirkanmaa Polytechnic (Finland) worked together to develop a new
      public health curriculum for Kyrgyzstan. Project activities took place in
      Kyrgyzstan and Europe throughout 2002-2004 and included English language
      training, fact finding visits to partner institutions and health services.
      Seminars and workshops were used to develop curriculum content and to support the
      design of new programs. A core curriculum team from KSMA, supported by European
      project staff, devised the new curriculum now on offer in Kyrgyzstan. RESULTS:
      The project achieved its three main goals: (1) development of a new public health
      curriculum; (2) establishment of an international forum for public health in
      Kyrgyzstan; and (3) dissemination of the project's findings via an international
      conference and the provision of web based support services. CONCLUSIONS: New
      courses in Preventive Medicine and Public Health Nursing at KSMA represent a
      significant cultural shift within public health in Central Asia, complementing
      the structural reforms of health care introduced in the 1990s. Emphasis on
      community engagement, health promotion and preventive action enhances knowledge,
      develops new skills and refocuses work practices for public health staff serving
      Kyrgyzstan's remote rural communities.

PMID- 16302845
TI  - Catabolism of endogenous and overexpressed APH1a and PEN2: evidence for
      artifactual involvement of the proteasome in the degradation of overexpressed
      proteins.
AB  - PS (presenilin)-dependent gamma-secretase occurs as a high-molecular-mass complex
      composed of either PS1 or PS2 associated with Nct (nicastrin), PEN2 (presenilin
      enhancer 2 homologue) and APH1 (anterior pharynx defective 1 homologue). Numerous
      reports have documented the very complicated physical and functional cross-talk
      between these proteins that ultimately governs the biological activity of the
      gamma-secretase, but very few studies examined the fate of the components of the
      complex. We show that, in both HEK-293 cells and the TSM1 neuronal cell line, the
      immunoreactivities of overexpressed myc-tagged-APH1a and -PEN2 were enhanced by
      the proteasome inhibitors ZIE and lactacystin, whereas a broad range of protease
      inhibitors had no effect. By contrast, proteasome inhibitors were totally unable
      to affect the cellular expression of endogenous APH1aL and PEN2 in HEK-293 cells,
      TSM1 and primary cultured cortical neurons. To explain this apparent discrepancy,
      we examined the degradation of myc-tagged-APH1a and -PEN2, in vitro, by cell
      extracts containing endogenous proteasome and by purified 20S proteasome.
      Strikingly, myc-tagged-APH1a and -PEN2 resist proteolysis by endogenous
      proteasome and purified 20S proteasome. We also show that endogenous PEN2
      expression was drastically higher in wild-type than in PS- and Nct-deficient
      fibroblasts and was enhanced by proteasome inhibitors only in the two deficient
      cell systems. However, here again, purified 20S proteasome appeared unable to
      cleave endogenous PEN2 present in PS-deficient fibroblasts. The levels of
      endogenous APH1aL-like immunoreactivity were not modified by proteasome
      inhibitors and were unaffected by PS deficiency. Altogether, our results indicate
      that endogenous PEN2 and APH1aL do not undergo proteasomal degradation under
      physiological conditions in HEK-293 cells, TSM1 cells and fibroblasts and that
      the clearance of PEN2 in PS- and Nct-deficient fibroblasts is not mediated by 20S
      proteasome. Whether the 26S proteasome participates to PEN2 proteolysis in
      deficient fibroblasts remains to be established.

PMID- 16302846
TI  - Side-effects of L-dopa on venous tone in Parkinson's disease: a leg-weighing
      assessment.
AB  - In the present study, the effects of L-dopa treatment on cardiovascular variables
      and peripheral venous tone were assessed in 13 patients with Parkinson's disease
      (PD) with Hoehn and Yahr stages 1-4. Patients were investigated once with their
      regular treatment and once after 12 h of interruption of L-dopa treatment. L-Dopa
      intake significantly reduced systolic and diastolic blood pressure, heart rate
      and plasma noradrenaline and adrenaline in both the supine and upright (60
      degrees ) positions. A significant reduction in stroke volume and cardiac output
      was also seen with L-dopa. The vascular status of the legs was assessed through
      thigh compression during leg weighing, a new technique developed in our
      laboratory. Healthy subjects were used to demonstrate that this technique
      provided reproducible results, consistent with those provided by strain gauge
      plethysmography of the calf. When using this technique in patients with PD, L
      dopa caused a significant lowering of vascular tone in the lower limbs as shown,
      in particular, by an increase in venous distensibility. Combined with the results
      of the orthostatic tilting, these findings support that the treatment-linked
      lowering of plasma noradrenaline in patients with PD was concomitant with a
      significant reduction in blood pressure, heart rate and vascular tone in the
      lower limbs. These pharmacological side-effects contributed to reduce venous
      return and arterial blood pressure which, together with a lowered heart rate,
      worsened the haemodynamic status.

PMID- 16302847
TI  - Agrobacterium-mediated delivery of marker genes to Phanerochaete chrysosporium
      mycelial pellets: a model transformation system for white-rot fungi.
AB  - The lack of an efficient transformation system in filamentous fungi is one of the
      major problems in carrying out cloning and expression of genes to produce a value
      added product at the commercial level. Therefore an attempt has been made to
      develop an efficient, convenient and expeditious genetic transformation system
      for successful transfer of transferred DNA, carrying the genes coding for GUS
      (beta-glucuronidase) (uidA), green fluorescent protein (gfp) and hygromycin
      phosphotransferase (hpt) to the nuclear genome of Phanerochaete chrysosporium, a
      widely studied lignin-degrading white-rot fungus. The transformation of the
      marker gene was confirmed through GUS, PCR and Southern-blot hybridization.
      Transformation with acetosyringone, in the presence of light with partial
      bleaching for 1 h, were found to be a better combination for fungal
      transformation with 48% efficiency. The agro-transformation method to transform
      the modified mycelial pellets offers a practical means for exploiting transgenic
      approaches in genetic manipulation and improvement of P. chrysosporium, a model
      white-rot fungus. Moreover, it has the potential to overcome the technical
      hurdles in genetic manipulation to bio-technologically exploit many other
      filamentous fungi of industrial importance.

PMID- 16302848
TI  - Effects of peptide C corresponding to the Glu724-Pro760 region of the II-III loop
      of the DHP (dihydropyridine) receptor alpha1 subunit on the domain- switch
      mediated activation of RyR1 (ryanodine receptor 1) Ca2+ channels.
AB  - The Leu720-Leu764 region of the II-III loop of the dihydropyridine receptor is
      believed to be important for both orthograde and retrograde communications with
      the RyR (ryanodine receptor), but its actual role has not yet been resolved. Our
      recent studies suggest that voltage-dependent activation of the RyR channel is
      mediated by a pair of interacting N-terminal and central domains, designated as
      the 'domain switch'. To investigate the effect of peptide C (a peptide
      corresponding to residues Glu724-Pro760) on domain- switch-mediated activation of
      the RyR, we measured Ca2+ release induced by DP (domain peptide) 1 or DP4 (which
      activates the RyR by mediation of the domain switch) and followed the Ca2+
      release time course using a luminal Ca2+ probe (chlortetracycline) under Ca2+
      clamped conditions. Peptide C produced a significant potentiation of the domain
      switch-mediated Ca2+ release, provided that the Ca2+ concentration was
      sufficiently low (e.g. 0.1 microM) and the Ca2+ channel was only partially
      activated by the domain peptide. However, at micromolar Ca2+ concentrations,
      peptide C inhibits activation. Covalent cross-linking of fluorescently labelled
      peptide C to the RyR and screening of the fluorescently labelled tryptic
      fragments permitted us to localize the peptide-C-binding site to residues 450
      1400, which may represent the primary region involved in physical coupling. Based
      on the above findings, we propose that the physiological role of residues Glu724
      Pro760 is to facilitate depolarization-induced and domain-switch-mediated RyR
      activation at sub- or near-threshold concentrations of cytoplasmic Ca2+ and to
      suppress activation upon an increase of cytoplasmic Ca2+.

PMID- 16302849
TI  - L-cysteate sulpho-lyase, a widespread pyridoxal 5'-phosphate-coupled
      desulphonative enzyme purified from Silicibacter pomeroyi DSS-3(T).
AB  - Quantitative utilization of L-cysteate (2-amino-3-sulphopropionate) as the sole
      source of carbon and energy for growth of the aerobic, marine bacterium
      Silicibacter pomeroyi DSS-3(T) was observed. The sulphonate moiety was recovered
      in the medium largely as sulphite, and the appropriate amount of the ammonium ion
      was also observed. Genes [suyAB (3-sulpholactate sulpho-lyase)] encoding the
      known desulphonation reaction in cysteate degradation were absent from the
      genome, but a homologue of a putative sulphate exporter gene (suyZ) was found,
      and its neighbour, annotated as a D-cysteine desulphhydrase, was postulated to
      encode pyridoxal 5'-phosphate-coupled L-cysteate sulpho-lyase (CuyA), a novel
      enzyme. Inducible CuyA was detected in cysteate-grown cells. The enzyme released
      equimolar pyruvate, sulphite and the ammonium ion from L-cysteate and was
      purified to homogeneity by anion-exchange, hydrophobic-interaction and gel
      filtration chromatography. The N-terminal amino acid sequence of this 39-kDa
      subunit confirmed the identification of the cuyA gene. The native enzyme was
      soluble and homomultimeric. The K(m)-value for L-cysteate was high (11.7 mM) and
      the enzyme also catalysed the D-cysteine desulphhydrase reaction. The gene cuyZ,
      encoding the putative sulphite exporter, was co-transcribed with cuyA. Sulphite
      was exported despite the presence of a ferricyanide-coupled sulphite
      dehydrogenase. CuyA was found in many bacteria that utilize cysteate.

PMID- 16302850
TI  - In situ-produced 7-chlorokynurenate has different effects on evoked responses in
      rats with limbic epilepsy in comparison to naive controls.
AB  - PURPOSE: Uncontrolled epilepsy remains a significant health concern and requires
      new approaches to therapy. N-methyl-d-aspartate (NMDA) receptor blockade has been
      considered, but the adverse cognitive and behavioral effects of conventional NMDA
      receptor antagonists have prevented the development of clinically useful
      compounds. An alternative approach may be the blockade of the glycine coagonist
      ("glycine(B)") site of the NMDA receptor. METHODS: As a first step in the
      exploration of this approach, we examined the effect of 4-chloro-kynurenine (4-Cl
      KYN), which is converted by astrocytes to the potent NMDA glycine-site antagonist
      7-chloro-kynurenic acid (7-Cl-KYNA), on the in vivo epileptiform evoked
      potentials in the CA1 region of rats with chronic limbic epilepsy (CLE). 4-Cl-KYN
      (100 mg/kg) was administered intraperitoneally to naive and epileptic rats.
      Evoked potentials were induced in area CA1 of the hippocampus by electrical
      stimulation of the midline region of the thalamus. Simultaneous microdialysis was
      performed in the contralateral hippocampus to determine the extracellular levels
      of 7-Cl-KYNA over the course of the experiment. RESULTS: Administration of 4-Cl
      KYN caused a significant reduction in the amplitude of the population spike and
      in the number of population spikes in epileptic animals (p < 0.01) but had no
      effect on the evoked response in naive rats. In contrast, 4-Cl-KYN significantly
      altered the paired response in naive animals (p < 0.01), but had no significant
      effect on this parameter in epileptic animals. The levels of 7-Cl-KYNA measured
      achieved known pharmacologically effective concentrations and paralleled the
      observed physiological effects. CONCLUSIONS: The use of glial cells for the
      neosynthesis and local delivery of neuroactive compounds may be a viable strategy
      for the treatment of limbic epilepsy. These results also underscore the unique
      pharmacology of neurons in epilepsy.

PMID- 16302851
TI  - Expression of neural stem cell surface marker CD133 in balloon cells of human
      focal cortical dysplasia.
AB  - PURPOSE: Focal cortical dysplasia (CD) is characterized by the presence of
      dysmorphic neurons, laminar and columnar disorganization. A few patients with CD
      have balloon cells intermixed with dysmorphic neurons. The cellular
      characteristics of balloon cells remain unknown. This study was intended to
      determine further the cellular characteristics of balloon cells. METHODS:
      Neocortical tissue resected from five patients with medically intractable focal
      epilepsy due to CD was studied. The presence of balloon cells (large opalescent
      cells with eccentric nuclei) was confirmed in all five patients by using
      cresylecht violet staining. Immunocytochemistry used antibodies against markers
      of pluripotential stem cells (CD133), multipotential progenitor cells (nestin),
      antiapoptotic gene products (Bcl-2), immature neurons (beta-tubulin 3, TUJ1),
      immature glia (vimentin), mature neurons (MAP2 and NeuN), and astrocytes (glial
      fibrillary acidic protein; GFAP). RESULTS: Balloon cells (BCs) were found to be
      immunoreactive to Bcl-2 (46%), vimentin (41%), Nestin (28%), CD133 (28%), MAP2
      (27%), GFAP (14%), and TUJ1 (10%). An extremely small number of BCs were
      immunopositive for NeuN. Confocal double labeling showed that balloon cells were
      dually immunopositive for CD133/nestin; CD133/GFAP; CD133/Bcl-2, and nestin/GFAP.
      CONCLUSIONS: These results show that balloon cells are heterogeneous cell
      populations expressing cell-surface markers for pluripotential stem cells and
      proteins for multipotent progenitors, or immature neurons/glia. The presence of
      stem cell/progenitor markers in the balloon cells could be due to a persistent
      postnatal neurogenesis or early embryonic insult that resulted in arrest of
      proliferation/differentiation at their early stages. Additionally, the
      coexpression of Bcl-2 in CD133-positive balloon cells suggests that a resistance
      to programmed cell death may be involved in the pathogenesis of cortical
      dysplasia.

PMID- 16302852
TI  - Brain inflammation in epilepsy: experimental and clinical evidence.
AB  - Inflammatory reactions occur in the brain in various CNS diseases, including
      autoimmune, neurodegenerative, and epileptic disorders. Proinflammatory and
      antiinflammatory cytokines and related molecules have been described in CNS and
      plasma, in experimental models of seizures and in clinical cases of epilepsy.
      Inflammation involves both the innate and the adaptive immune systems and shares
      molecules and pathways also activated by systemic infection. Experimental studies
      in rodents show that inflammatory reactions in the brain can enhance neuronal
      excitability, impair cell survival, and increase the permeability of the blood
      brain barrier to blood-borne molecules and cells. Moreover, some antiinflammatory
      treatments reduce seizures in experimental models and, in some instances, in
      clinical cases of epilepsy. However, inflammatory reactions in brain also can be
      beneficial, depending on the tissue microenvironment, the inflammatory mediators
      produced in injured tissue, the functional status of the target cells, and the
      length of time the tissue is exposed to inflammation. We provide an overview of
      the current knowledge in this field and attempt to bridge experimental and
      clinical evidence to discuss critically the possibility that inflammation may be
      a common factor contributing, or predisposing, to the occurrence of seizures and
      cell death, in various forms of epilepsy of different etiologies. The elucidation
      of this aspect may open new perspectives for the pharmacologic treatment of
      seizures.

PMID- 16302853
TI  - In vivo epileptogenicity of focal cortical dysplasia: a direct cortical paired
      stimulation study.
AB  - PURPOSE: Alternation of the intracortical inhibitory and excitatory mechanisms in
      focal cortical dysplasia (FCD) has not been well elucidated in vivo in humans. We
      investigated in vivo alternation of these mechanisms in epileptogenesis of FCD by
      means of paired-pulse direct cortical electrical stimulation. METHODS: A 31-year
      old man with FCD at the left foot primary somatosensory (SI) and motor areas who
      underwent invasive monitoring with subdural electrodes was studied. By means of
      subdural electrodes, paired-pulse electrical stimulation was performed at the
      epileptic focus (foot SI) and control cortex (hand SI) with interstimulus
      interval (ISI) of 1-100 ms. Instead of using motor evoked potentials to
      investigate the degree of cortical excitability in response to motor cortex
      stimulation, we evaluated the size change of corticocortical evoked potentials
      (CCEPs), which are elicited at the adjacent cortex by direct cortical stimulation
      via fiber projection and thus reflect direct and indirect excitation of
      corticocortical projection neurons at the site of stimulation. RESULTS: During
      the interictal state, paired-pulse stimulation of the focus revealed abnormally
      enhanced intracortical inhibition at ISI of 1-10 ms (maximum, 22%) compared with
      control stimulation of the hand SI (ISI of 1-2 ms; maximum, 18%) (p < 0.01).
      While the patient was having the somatosensory aura that later evolved into the
      left-leg clonic seizure, single and paired stimulation at the focus showed
      increased cortical excitability (enlarged CCEP) and decreased intracortical
      inhibition, respectively. CONCLUSIONS: During the aura, interictally enhanced
      intracortical inhibition at the focus was replaced by increased cortical
      excitability and decreased intracortical inhibition, suggesting increased net
      intrinsic epileptogenicity during seizure generation in this patient with FCD.

PMID- 16302854
TI  - Ipsilateral head deviation in frontal lobe seizures.
AB  - PURPOSE: The lateralizing value of ictal head deviation (HD) in frontal lobe
      epilepsy (FLE) is a matter of debate. Although FLE is typically associated with
      tonic or clonic HD contralateral to seizure onset, ipsilateral HD has been noted
      in numerous reports. Whether both types of HD can be distinguished according to
      their clinical patterns has not yet been specifically investigated. METHODS: We
      studied the clinical pattern and time of occurrence of HD of 129 seizures in 13
      consecutive patients, who underwent successful surgery for FLE, including 12
      investigated with an intracerebral stereotactic EEG procedure. RESULTS: Ictal HD
      was ipsilateral to the epileptogenic zone (EZ) in four (30%) patients and 27
      (20.9%) seizures and contralateral in five (38%) patients and 15 (11.6%)
      seizures. Ipsilateral HD was rarely tonic and never associated with clonic
      manifestation. Contralateral HD was always tonic, unnatural, and associated with
      hemifacial clonic movements in 86% of seizures. Ipsilateral HD occurred earlier
      than contralateral HD (p < 0.03), with a mean delay of 1 +/- 2 s after the first
      detectable ictal sign, as compared with a delay of 17 +/- 11 s for contralateral
      HD. Moreover, ipsilateral HD always occurred before contralateral HD when both
      signs coexisted in the same seizure. Our patients with ipsilateral HD
      demonstrated either an anterior or dorsolateral frontal EZ. CONCLUSIONS:
      Ipsilateral HD is a common ictal sign during FLE and can be distinguished from
      contralateral HD by its time of occurrence at or immediately after seizure onset
      and its lacking association with clonic movements.

PMID- 16302855
TI  - Hippocampal formation involvement in a language-activation task in patients with
      mesial temporal lobe epilepsy.
AB  - PURPOSE: The study aims to explore the contribution of the hippocampal formation
      to the retained language-comprehension network in patients with unilateral mesial
      temporal lobe epilepsy (TLE). METHODS: We performed a functional magnetic
      resonance (MRI) study based on a language comprehension paradigm in 45 right
      handed patients with unilateral mesial TLE and 35 healthy control subjects.
      Activations in the hippocampal formations in both hemispheres were analyzed for
      each subject as well as for groups of left TLE, right TLE, and controls. RESULTS:
      In sum, 82% of TLE patients displayed hippocampal activations. A significant
      difference in hippocampal activation between left and right TLE was found: Right
      TLE patients showed increased activity in the left hippocampal formation compared
      with left TLE patients. In contrast, patients with left TLE did not show
      increased activity in the right hippocampal formation compared with right TLE
      patients. In comparison with a healthy control group, right TLE patients
      activated the left hippocampal formation to a greater extent, whereas patients
      with left TLE did not activate the right hippocampal formation to a greater
      degree. These findings point to an increased involvement of the left hippocampal
      formation during a language-comprehension task in right TLE patients. In
      contrast, left TLE in right-handed patients seems not associated with an enhanced
      involvement of the right hippocampal formation in retained language
      comprehension. CONCLUSIONS: These findings suggest that effective language
      comprehension in right-handed subjects with TLE depends on the involvement of the
      left hippocampal formation and underline the risks of postoperative language
      decline in patients with left TLE.

PMID- 16302856
TI  - Unilateral intracarotid amobarbital procedure for language lateralization.
AB  - PURPOSE: The determination of language dominance as part of the presurgical
      workup of patients with pharmacoresistant epilepsies has experienced fundamental
      changes. With the introduction of noninvasive functional magnetic resonance
      imaging (fMRI), the number of patients receiving intracarotid amobarbital
      procedures (IAPs) for assessment of language dominance has decreased
      considerably. However, recent studies show that because of methodologic
      limitations of fMRI, IAP remains an important tool for language lateralization.
      The current study examines whether unilateral instead of bilateral IAP is an
      adequate way to apply IAP with reduced invasiveness. METHODS: We retrospectively
      examine the predictive value of unilateral IAP for the results of bilateral IAP
      based on a sample of 75 patients with various types of language dominance. Target
      parameters are the prediction of the language-dominant hemisphere and the
      identification of patients with atypical language dominance. For language
      assessment based on unilateral IAP, we introduce the measure hemispheric language
      capacity (HLC). RESULTS: Unilateral IAP performed on the side of intended surgery
      quantifies language capacity contralateral to the intended surgery. It detects
      atypical (bilateral or right) language dominance in the majority of patients.
      Experience with a separate series of 107 patients requiring presurgical language
      lateralization shows that in >80%, bilateral IAPs are redundant. CONCLUSIONS:
      Unilateral IAP is principally sufficient for language lateralization in the
      presurgical evaluation of patients with pharmacoresistant epilepsies. Necessity
      of bilateral IAP is restricted to few indications (e.g., callosotomy). In times
      of noninvasive language lateralization, we propose unilateral IAP as the method
      of choice for the verification of doubtful (bilateral) fMRI activation patterns.

PMID- 16302857
TI  - Utility of the Boston naming test in predicting ultimate side of surgery in
      patients with medically intractable temporal lobe epilepsy.
AB  - PURPOSE: Confrontation naming tasks have long been presumed to be sensitive to
      left temporal dysfunction and, consequently, are frequently used in the
      evaluation of surgical epilepsy patients. Despite wide and frequent use, few
      studies have examined the utility of confrontation naming tasks in individuals
      with temporal lobe epilepsy (TLE). METHODS: The current study examined the
      presurgical Boston Naming Test (BNT) performance of 217 right-handed adult
      patients with intractable TLE (left, 108; right, 109) to determine the utility of
      this measure in predicting ultimate side of surgery. RESULTS: The results support
      the clinical utility of the BNT in determining ultimate side of surgery and
      suggest that the BNT has incremental validity over and above presurgical delayed
      memory and intelligence scores. This relation was found to be moderated by Full
      Scale IQ (FSIQ), age at seizure onset, and duration of epilepsy. The use of a
      logistic regression equation to predict side of surgery revealed that prediction
      of left temporal surgery was best among patients with low BNT scores, high FSIQs,
      and late age at seizure onset. In contrast, right temporal surgery was best
      predicted among patients with high BNT scores, low FSIQs, and short duration of
      epilepsy. CONCLUSIONS: This study supports the clinical utility of the BNT in the
      preoperative evaluation of candidates for TLE surgery and highlights the
      importance of examining potential moderating variables when making predictions
      about side of surgery. This study further provides clinicians with a regression
      equation that can be used to predict side of surgery in patients with temporal
      lobe epilepsy.

PMID- 16302858
TI  - Cognitive decline in severe intractable epilepsy.
AB  - PURPOSE: To explore the relation between seizure-related variables and cognitive
      change in patients with severe intractable epilepsy. METHODS: A retrospective
      analysis of data from 136 patients who had undergone a cognitive assessment on
      two occasions at an interval of > or =10 years. Cognitive measures included tests
      of memory and executive skills in addition to intelligence quotients (IQ).
      Details were available regarding seizure type and frequency in the intertest
      interval. RESULTS: Cognitive decline was severe and occurred across a wide range
      of cognitive functions. The frequency of generalised tonic-clonic seizures was
      the strongest predictor of decline. Complex partial seizure frequency was
      associated with a decline in memory and executive skills but not in IQ. Seizure
      related head injuries and advancing age carried a poor cognitive prognosis,
      whereas periods of remission were associated with a better cognitive outcome.
      Early age at onset was not implicated, and duration of epilepsy was a much less
      potent predictor of cognitive decline than has been reported in cross-sectional
      studies. No evidence indicated that a higher level of cognitive function
      protected against cognitive decline. CONCLUSIONS: Our findings, together with
      those from animal studies and surgically treated patients, suggest that seizures
      can have a direct adverse effect on cognition and that good seizure control even
      after years of intractability can have a beneficial impact on cognitive
      prognosis. This study was based on individuals who merited two cognitive
      assessments > or =10 years apart and hence is biased in favor of those with the
      most severe forms of refractory epilepsy and those with decline.

PMID- 16302859
TI  - Measuring outcome in psychogenic nonepileptic seizures: how relevant is seizure
      remission?
AB  - PURPOSE: To examine whether seizure remission is a comprehensive marker of
      outcome in psychogenic nonepileptic seizures (PNESs). METHODS: A postal
      questionnaire was returned by 147 patients with PNESs a mean of 4.2 years after
      diagnosis (mean age at follow-up, 38.1 years). The proportion of patients who
      were "unproductive" (receiving health-related state benefits) at follow-up was
      determined, with a comparison of markers of ongoing psychopathology (Global
      Severity Index, anxiety and depression scores of the Symptom Checklist 90,
      Somatization Index DSM of the SOMS-2) in three outcome groups: group 1,
      continuing seizures; group 2, seizures stopped but patients "unproductive;" and
      group 3, seizures stopped, patients "productive." RESULTS: Of the patients, 71.4%
      continued to have seizures, and 28.6% had achieved seizure remission; 60.0% of
      patients with continuing seizures and 42.7% of patients in remission were
      "unproductive" (difference, NS). Ongoing psychopathology was related to the
      factor "group membership" with higher values in groups 2 and 3 than in group 1
      (GSI, p < 0.001; anxiety, p = 0.01; depression, p = 0.02; Somatization Index DSM,
      p < 0.001). Across all patients and in the subgroup with PNESs and additional
      epilepsy, differences were significant only between groups 2 and 3, not between
      groups 1 and 2. In patients with PNESs alone, differences were significant only
      between groups 1 and 2. CONCLUSIONS: Seizure remission is not a comprehensive
      measure of good medical or psychosocial outcome in PNESs. Nearly half the
      patients who become seizure free remain unproductive. Many of these patients
      continue to report symptoms of psychopathology. Seizure control should not be the
      only focus of treatment in clinical practice or outcome observation in research
      studies.

PMID- 16302860
TI  - Childhood absence epilepsy: evolution and prognostic factors.
AB  - PURPOSE: To evaluate how diagnostic criteria influence remission rates for
      patients with childhood absence epilepsy (CAE) and to assess clinical and EEG
      parameters as predictors of outcome. METHODS: One hundred nineteen patients were
      diagnosed with CAE, according to International League Against Epilepsy (ILAE)
      classification criteria. They were subsequently evaluated according to stricter
      diagnostic criteria. Sixty-two subjects fulfilled these criteria as group 2; 57
      did not and constituted group 1. Diagnostic parameters that prevented patients of
      group 1 from entering group 2, and variables such as sex, familial history of
      generalized epilepsy, and personal history of febrile convulsions also were
      tested as prognostic factors for terminal remission. RESULTS: Compared with those
      in group 1, patients of group 2 had significantly higher rates of seizure control
      (95% vs. 77%), higher rates of terminal remission (82% vs. 51%), fewer
      generalized tonic-clonic seizures (8% vs. 30%), and shorter mean periods of
      treatment (2.2 vs. 3.8 years). Significantly fewer patients were receiving
      polytherapy in group 2 than in group 1 (11% vs. 47%), and fewer patients had
      seizure relapses at antiepileptic drug discontinuation (0 vs. 22%). CONCLUSIONS:
      Remission rates of patients with CAE are greatly influenced by the classification
      criteria used for selection. Stricter diagnostic criteria allow the definition of
      a homogeneous group of patients with excellent prognosis. Factors predicting
      unfavorable prognosis were generalized tonic-clonic seizures in the active stage
      of absences, myoclonic jerks, eyelid myoclonia or perioral myoclonia, and EEG
      features atypical for CAE.

PMID- 16302861
TI  - Vagus nerve stimulation induces concomitant respiratory alterations and a
      decrease in SaO2 in children.
AB  - PURPOSE: To analyze respiratory alterations and effects on SaO(2) caused by vagus
      nerve stimulation (VNS) in children with epilepsy. METHODS: Polysomnographic
      recordings, including electroencephalography, thoracoabdominal distention, nasal
      airflow, SaO(2), and VNS artifact were evaluated in 10 children with
      pharmacoresistant epilepsy treated with VNS. RESULTS: Each VNS caused a
      significant increase in respiratory frequency (p < 0.05) throughout the
      stimulation period and a decrease in thoracoabdominal-distention amplitude (p <
      0.05), especially at the beginning of the stimulation. These respiratory
      alterations induced a decrease in SaO(2) from 1 to 5%. The effects of VNS on
      respiration differed significantly between rapid-eye-movement (REM) and non-REM
      (NREM) sleep states. CONCLUSIONS: VNS caused a pronounced change in respiration
      in children with epilepsy, and this induced a decrease in SaO(2). It is possible
      that VNS has a neuroprotective effect, and this possibility calls for further
      investigation.

PMID- 16302862
TI  - Fasting versus gradual initiation of the ketogenic diet: a prospective,
      randomized clinical trial of efficacy.
AB  - PURPOSE: The ketogenic diet (KD) is a 90% fat diet that is an effective treatment
      for intractable epilepsy. Rapid initiation of the KD requires hospital admission
      because of the complexity of the protocol and frequent mild and moderate adverse
      events. The purpose of the study was to compare the efficacy of a gradual KD
      initiation with the standard KD initiation preceded by a 24- to 48-h fast.
      METHODS: Children ages 1 to 14 years with intractable epilepsy were randomized to
      a fasting initiation (FAST-KD) or gradual initiation (GRAD-KD). Baseline seizure
      activity was recorded daily for 28 days before admission and continued for the 3
      month duration of the study. Effectiveness was measured in two ways: (a) the
      proportion of subjects with >50% reduction in target seizure type from baseline
      to 3-month evaluation, and (b) percentage reduction in the frequency of the
      target seizure type from baseline to 3-month evaluation. Blood glucose was
      assessed q4 to 6h, and weights, electrolytes, hydration status, vomiting, acid
      balance, need for interventions (citric acid and sodium citrates (Bicitra) and IV
      fluids) were assessed daily. Fisher's exact tests were used to examine the
      association between protocol and occurrence of adverse events, and longitudinal
      mixed-effects models were used to look for trends in tolerability data over time.
      RESULTS: Forty-eight subjects, 24 in each arm, were randomized. In the FAST-KD
      protocol, 58% of the children had >50% reduction in the target seizure type at 3
      months, and 21% were seizure free. In the GRAD-KD protocol, 67% had a >50%
      reduction at 3 months, and 21% were seizure free. The two protocols were
      equivalent in efficacy (p = 0.033). At 3 months, the FAST-KD median percentage
      seizure reduction rate was 78% (ranging from 100% reduction to 73% increase in
      seizures per week) and was 94% (ranging from 100% reduction to 161% increase in
      seizures per week) for the GRAD-KD protocol. By using a logarithmic transformed
      percentage reduction rate and an equivalence limit difference of 20%, the
      efficacy of the two protocols was equivalent (p = 0.0002). Children in the GRAD
      protocol lost significantly less weight (p = 0.006), and had fewer and less
      severe episodes of hypoglycemia (p < 0.001), fewer treatments for acidosis
      (citric acid and sodium citrates) (p < 0.04) and dehydration (IV fluids) (p <
      0.04), but no difference in vomiting was noted. CONCLUSIONS: These data suggest
      that in children with intractable epilepsy, a gradual initiation results in fewer
      adverse events and is tolerated better overall while maintaining the efficacy of
      the KD.

PMID- 16302863
TI  - The impact of epilepsy on health status among younger and older adults.
AB  - PURPOSE: The incidence of epilepsy is highest among the elderly, yet our
      understanding of the impact of epilepsy is based predominantly on inferences from
      studies of younger adults. This study examines the impact of epilepsy on
      patients' subjective health status in a population that includes both younger and
      older adults. METHODS: We used national administrative and survey databases from
      the Veterans Health Administration to examine health status as measured by a
      modification of the SF-36 (RV-36) in patients from three age cohorts: young
      adults (18-40 years), middle-aged adults (41-64 years), and older adults (65
      years and older). Because chronicity of epilepsy may influence these outcomes, we
      compared scores for patients with new-onset epilepsy, chronic epilepsy, and no
      epilepsy by using analysis of covariance, controlling for patient demographic and
      clinical characteristics that may also affect health status. RESULTS: With the
      exception of physical status measures, older adults appeared to cope better with
      their epilepsy than did middle-aged patients. Young adults with new-onset
      epilepsy reported poor general health and worse mental health, but high levels of
      physical function and physical activity. Middle-aged patients with new-onset
      epilepsy scored lowest in all domains, and their peers with chronic epilepsy also
      reported poor general physical health and emotional functioning. CONCLUSIONS:
      Although having fewer physiologic reserves, older adults appeared most resilient
      in facing this chronic illness, and middle-aged adults fared the worst.
      Interventions to improve quality of life among patients with epilepsy should be
      tailored to age and epilepsy chronicity.

PMID- 16302864
TI  - Prevalence and characteristics of epilepsy in the Aeolian islands.
AB  - PURPOSE: To estimate the prevalence and define the clinical characteristics of
      epileptic disorders in the 13,431 residents of the Sicilian Aeolian archipelago,
      on June 1, 1999. METHODS: All established or suspected cases were identified by
      the neurologists of our working group from available medical information sources.
      Possible epilepsy cases were then evaluated by the epileptologists by using a
      standardized questionnaire. The patients were further reviewed by the whole
      research team to confirm the clinical diagnosis. For a more detailed syndromic
      definition, some patients underwent EEG or neuroradiologic investigations or
      both. RESULTS: The crude point prevalence rate of active epilepsy was 3.13 (95%
      confidence interval, 2.2-4.2). The prevalence rate age-adjusted to the 2001
      Italian population was 3.01. Females had a slightly higher prevalence rate than
      did males. The highest age-specific prevalence was found in patients aged 5 to 14
      years (5.05) and in those aged 65 to 74 years (5.41). Partial seizures with or
      without secondary generalization were more common (61.7%) than were generalized
      seizures. Eighty-three percent of cases had symptomatic or cryptogenic
      localization-related epilepsies, and 8.5% had idiopathic (generalized or partial)
      epilepsies. Epilepsy was unclassified in 8.5% of cases. CONCLUSIONS: The
      prevalence of active epilepsy in the Aeolian islands is lower than that in other
      developed areas, including northern Italy, but is similar to that in Sicily.
      Partial seizures were the most common type, and localization-related symptomatic
      epilepsies were the largest syndromic category.

PMID- 16302865
TI  - Victor Horsley's contribution to Jacksonian epileptology.
AB  - PURPOSE: To describe Victor Horsley's contribution to John Hughlings Jackson's
      understanding of the mechanisms involved in the generalization of convulsive
      epileptic seizures. METHODS: I reviewed Horsley's writings and other relevant
      late 19th century medical literature. RESULTS: Horsley's combination of
      strategically sited surgical lesions and cerebral cortex stimulation studies in
      experimental animals showed that, contrary to Hughlings Jackson's earlier belief,
      epileptic activity arising in one cerebral hemisphere had to spread to the
      contralateral hemisphere before bilateral convulsing could occur. CONCLUSIONS: On
      the basis of well-designed experiments, Horsley made a major contribution to the
      understanding of epileptic seizure propagation mechanisms.

PMID- 16302866
TI  - Effect of plasma exchange on carbamazepine levels in a patient with myasthenia
      gravis and epilepsy.
AB  - PURPOSE: Patients taking antiepileptic medications may require plasma exchange
      (PEX) for treatment of an unrelated condition. METHODS: We studied total serum
      levels of carbamazepine (CBZ) serially, before and after five PEX cycles, in an
      epilepsy patient who underwent PEX for myasthenia gravis. RESULTS: A small but
      consistent reduction in the CBZ levels was noted immediately after each cycle,
      and a gradual and cumulative increase in the serum levels was observed over the
      duration of the PEX cycles. CONCLUSIONS: We conclude that alterations in the
      serum CBZ levels with PEX are not clinically significant to merit adjustment of
      the CBZ dose.

PMID- 16302867
TI  - Nonketotic hyperglycemia-related epilepsia partialis continua with ictal
      unilateral parietal hyperperfusion.

PMID- 16302869
TI  - Idiopathic generalized epilepsies: a review and modern approach.

PMID- 16302870
TI  - Historical aspects of idiopathic generalized epilepsies.
AB  - Early in these proceedings, the origin of the three terms in the title,
      "idiopathic generalized epilepsy," is discussed with respect to their
      significance over time, and typical misunderstandings. In the mid-20th century, a
      rather chaotic use of a multitude of often loosely defined terms had developed,
      which increasingly became an obstacle to a meaningful international discussion.
      The International League against Epilepsy (ILAE) took the initiative to develop
      an internationally accepted terminology with a classification system consisting
      of a classification of seizures (1981) and a classification of syndromes (1989).
      The Idiopathic Generalized Epilepsies are one of its four major groups emerging
      from a double dichotomy of generalized versus localization-related and idiopathic
      versus symptomatic. The inclusion of biologic aspects such as syndrome-specific
      ages of onset ("age-related syndromes") or syndrome-specific relations of seizure
      occurrence to the sleep-wake cycle ("Epilepsy with Grand Mal on Awaking") meant
      that the syndrome classification merged the more biological views of the German
      school with the more neurophysiological ones of the French. Apart from
      establishing a common international language concerning epilepsy, the
      International Classification of Epilepsies and Epileptic Syndromes became an
      important stimulator of research, especially concerning the idiopathic
      epilepsies. In particular, genetic and functional imaging investigations aim at a
      better understanding of these conditions. It is now understood that most
      idiopathic syndromes have a--sometimes complex--genetic background, but we are
      also becoming aware of the inappropriateness of the time-honored term
      "generalized" and part of our dichotomies. Both localization-related and
      "generalized" idiopathic epilepsies seem to share a principle of ictogenesis
      based on functional anatomic pathogenic networks, and we seem to move toward
      understanding them as functional system disorders of the brain.

PMID- 16302871
TI  - Epidemiology of idiopathic generalized epilepsies.
AB  - Idiopathic generalized epilepsies (IGEs) are a relatively new category of
      disorders defined by strict clinical and electroencephalogram (EEG) features
      proposed by the International League Against Epilepsy (ILAE) classification of
      epileptic syndromes. IGEs are usually easy to diagnose when clinical and EEG data
      are collected, but epilepsy is not synonymous with epileptic syndrome. So far,
      IGEs are studied in the large group of epilepsies of undetermined or unknown
      etiology although the genetic origin is now largely accepted. ILAE-proposed
      criteria are helpful in the clinical and therapeutic management of IGEs, but many
      epidemiologic studies still confuse the cryptogenic and idiopathic groups. Some
      syndromes in childhood, which are completely described by strict electroclinical
      criteria such as the absence epilepsies, juvenile myoclonic epilepsies, are
      usually included and analyzed in epidemiologic studies; however, other epileptic
      syndromes observed in infancy, such as benign familial neonatal seizures and
      benign myoclonic epilepsy in infancy, are quite rare and are usually excluded
      from epidemiologic surveys because they are difficult to describe completely in
      electro-clinical terms. Another strong limitation in the study of epidemiology of
      IGEs is the lack of EEG data, either because EEG is not available or the routine
      EEG is normal. This is particularly relevant in the inclusion of patients with
      only tonic-clonic seizures. IGEs encompass several different syndromes, and a few
      patients shift from one phenotype to another. The overlapping of some syndromes
      during infancy and adolescence increased the difficulty to individualize strictly
      the correct syndrome. Many discrepancies can be observed in the distribution of
      the different syndromes included in the group of IGEs, because the strict
      criteria for classifying these syndromes proposed by the ILAE are often not
      respected. With this understanding, the general frequency of IGEs can be assessed
      at 15-20% of all epilepsies. The frequency and the distribution of incidence and
      prevalence of the different syndromes are tentatively reported and discussed.
      When the term idiopathic is used following the restrictive ILAE criteria, the
      mortality data concerning patients with idiopathic epilepsies do not show an
      increased standardized mortality ratio.

PMID- 16302872
TI  - Genetics of idiopathic generalized epilepsies.
AB  - The idiopathic generalized epilepsies (IGEs) are considered to be primarily
      genetic in origin. They encompass a number of rare mendelian or monogenic
      epilepsies and more common forms which are familial but manifest as complex, non
      mendelian traits. Recent advances have demonstrated that many monogenic IGEs are
      ion channelopathies. These include benign familial neonatal convulsions due to
      mutations in KCNQ2 or KCNQ3, generalized epilepsy with febrile seizures plus due
      to mutations in SCN1A, SCN2A, SCN1B, and GABRG2, autosomal-dominant juvenile
      myoclonic epilepsy (JME) due to a mutation in GABRA1 and mutations in CLCN2
      associated with several IGE sub-types. There has also been progress in
      understanding the non-mendelian IGEs. A haplotype in the Malic Enzyme 2 gene,
      ME2, increases the risk for IGE in the homozygous state. Five missense mutations
      have been identified in EFHC1 in 6 of 44 families with JME. Rare sequence
      variants have been identified in CACNA1H in sporadic patients with childhood
      absence epilepsy in the Chinese Han population. These advances should lead to new
      approaches to diagnosis and treatment.

PMID- 16302873
TI  - Cellular and network mechanisms of spike-wave seizures.
AB  - Spike-wave seizures are often considered a relatively "pure" form of epilepsy,
      with a uniform defect present in all patients and involvement of the whole brain
      homogeneously. Here, we present evidence against these common misconceptions.
      Rather than a uniform disorder, spike-wave rhythms arise from the normal inherent
      network properties of brain excitatory and inhibitory circuits, where they can be
      provoked by many different insults in several different brain networks. Here we
      discuss several different cellular and molecular mechanisms that may contribute
      to the generation of spike-wave seizures, particularly in idiopathic generalized
      epilepsy. In addition, we discuss growing evidence that electrical, neuroimaging,
      and molecular changes in spike-wave seizures do not involve the entire brain
      homogeneously. Rather, spike-wave discharges occur selectively in some
      thalamocortical networks, while sparing others. It is hoped that improved
      understanding of the heterogeneous defects and selective brain regions involved
      will ultimately lead to more effective treatments for spike-wave seizures.

PMID- 16302874
TI  - Seizures of idiopathic generalized epilepsies.
AB  - Idiopathic generalized epilepsies (IGEs) comprise at least 40% of epilepsies in
      the United States, 20% in Mexico, and 8% in Central America. Here, we review
      seizure phenotypes across IGE syndromes, their response to treatment and advances
      in molecular genetics that influence nosology. Our review included the Medline
      database from 1945 to 2005 and our prospectively collected Genetic Epilepsy
      Studies (GENESS) Consortium database. Generalized seizures occur with different
      and similar semiologies, frequencies, and patterns, ages at onset, and outcomes
      in different IGEs, suggesting common neuroanatomical pathways for seizure
      phenotypes. However, the same seizure phenotypes respond differently to the same
      treatments in different IGEs, suggesting different molecular defects across
      syndromes. De novo mutations in SCN1A in sporadic Dravet syndrome and germline
      mutations in SCN1A, SCN1B, and SCN2A in generalized epilepsies with febrile
      seizures plus have unraveled the heterogenous myoclonic epilepsies of infancy and
      early childhood. Mutations in GABRA1, GABRG2, and GABRB3 are associated with
      absence seizures, while mutations in CLCN2 and myoclonin/EFHC1 substantiate
      juvenile myoclonic epilepsy as a clinical entity. Refined understanding of
      seizure phenotypes, their semiology, frequencies, and patterns together with the
      identification of molecular lesions in IGEs continue to accelerate the
      development of molecular epileptology.

PMID- 16302875
TI  - Idiopathic generalized epilepsies recognized by the International League Against
      Epilepsy.
AB  - There are eight syndromes currently recognized by the International League
      Against Epilepsy (ILAE) that would fit the original operational definition of
      idiopathic generalized epilepsy (IGE) syndromes, including benign myoclonic
      epilepsy in infancy; generalized epilepsy with febrile seizures plus, an entity
      in evolution; epilepsy with myoclonic absences; epilepsy with myoclonic-astatic
      seizures; childhood absence epilepsy; juvenile absence epilepsy; juvenile
      myoclonic epilepsy; and epilepsy with generalized tonic-clonic seizures only. All
      of these syndromes can be easily diagnosed when distinctive features are present.
      In some cases, such features are not present or only appear later in the course
      of the disease, making it challenging to distinguish the various syndromes.
      Electroencephalogram (EEG) is the most helpful laboratory test and often will
      strongly support the diagnosis of IGE, but may not be very helpful in
      discriminating between several of the syndromes with overlapping features. The
      same applies for genetic testing, although it is expected that further research
      exploring the genotype-phenotype relationships will enhance our abilities to make
      definitive diagnoses. At the current time, clinical features are still the
      cornerstone of accurate classification, and accurate classification, in turn, is
      the best predictor of outcome.

PMID- 16302876
TI  - Syndromes of idiopathic generalized epilepsies not recognized by the
      International League Against Epilepsy.
AB  - This chapter assesses probable epileptic syndromes within the idiopathic
      generalized epilepsies (IGE) that have not yet been recognized by the
      International League Against Epilepsy (ILAE). Jeavons syndrome, a purely reflex
      IGE that predominantly manifests with eyelid myoclonia and electroencephalogram
      (EEG) abnormalities on eye closure, is the most distinct and undisputed of the
      syndromes. Another is autosomal-dominant cortical tremor, myoclonus, and
      epilepsy, a purely monogenic disorder that has been documented in numerous
      reports, mainly from Japan and Italy. Perioral myclonia with absences is
      certainly a seizure type that may constitute an IGE syndrome when it is
      associated with a number of other clinical and EEG manifestations. Similarly,
      many patients suffer for years from phantom absences, a type of mild absence,
      before a first generalized tonic-clonic seizure that usually occurs in adulthood.
      Both perioral myoclonia with absences and phantom absences are clinically
      significant because they are probably lifelong and are associated with a very
      high incidence (around 50%) of absence status epilepticus that may escape
      diagnosis and appropriate treatment. The position of early childhood IGE, which
      manifests mainly with typical absence seizures that are distinctly different from
      childhood absence epilepsy and other recognized IGE syndromes, is less clear. The
      prevalence of these syndromes is significant. Their identification allows better
      clinical management and is important for genetic research and counselling. In
      addition, their recognition permits application of exclusion criteria for a more
      purified definition and a better understanding of the true boundaries of the
      other IGE syndromes already accepted by the ILAE.

PMID- 16302877
TI  - Photosensitivity in idiopathic generalized epilepsies.
AB  - Photosensitivity is an abnormal visual sensitivity of the brain in reaction to
      flickering light sources or patterns and is expressed in the electroencephalogram
      as generalized spike-and-wave discharge and in more susceptible individuals as
      clinical seizures. The most common types of seizures are generalized tonic
      clonic, followed by myoclonic and absence. The photosensitive epilepsies are
      classified as pure photosensitive, where seizures occur only with the flickering
      light source/pattern or during intermittent photic stimulation (IPS) in the
      laboratory, and epilepsy with photosensitivity, where spontaneous seizures also
      occur. Positive response to IPS in idiopathic epilepsy syndromes, which are
      included in the International Classification or are in development, is reported
      to range from 7.5% in juvenile absence epilepsy to 100% in pure photosensitive
      epilepsy. The treatment of photosensitivity and pure photosensitive epilepsy with
      rare seizures includes general and specific protective measures. For most
      patients, however, combination treatment with antiepileptic drugs is necessary.
      Valproic acid monotherapy has a success rate of 73-86%. Levetiracetam appears to
      be a new alternative therapeutic option. Clobazam, lamotrigine, ethosuximide, and
      topiramate also have been recommended as second-choice therapies.

PMID- 16302878
TI  - Status epilepticus in idiopathic generalized epilepsy.
AB  - Status epilepticus (SE) can take various forms in idiopathic generalized epilepsy
      (IGE), some of which forms also occur in symptomatic or focal epilepsies.
      Although the clinical semiology of the SE episodes may be similar in these
      different epilepsies, the frequency, response to treatment and prognosis differ.
      (a) Convulsive SE is surprisingly uncommon in IGE and much less common than in
      the secondarily generalized or partial epilepsies. Also, when it does occur, it
      usually responds rapidly to treatment. (b) Typical absence SE occurs only in
      patients with IGE (the subcategories with typical absence seizures) and also in
      the syndrome of de novo absence SE of late onset. This form of nonconvulsive SE
      should be differentiated from atypical absence SE, which occurs in the
      secondarily generalized epilepsy encephalopathies, and from complex partial SE
      which occurs in focal epilepsy. The clinical symptoms of these three types
      overlap but the prognosis and response to treatment are different. The mechanisms
      underlying absence SE are uncertain and may include both genetic and
      environmental factors. The termination of absence seizures has been hypothesized
      to be due to persistent activation of a depolarizing current in thalamocortical
      neurons that inactivates T-type calcium channels. SE could thus result from
      dysfunction of this channel or mechanisms that hyperpolarize thalamocortical
      neurons-these include decreased cortical inhibition, increased reticular thalamic
      neuronal activity or increased thalamocortical neuron GABA(B)-receptor
      activation. (c) Generalized electrographic SE is encountered in IGE in the
      syndrome of phantom absence with GTCS. It also occurs in ESES and in the Landau
      Kleffner syndrome. The seizure phenomenology overlaps with the focal SE of
      temporal or frontal lobe epilepsy. (d) Myoclonic SE is also uncommon in IGE but
      occurs in juvenile myoclonic epilepsy. It is more commonly encountered in
      progressive myoclonic epilepsies, myoclonic-astatic epilepsy and in the Dravet
      syndrome. (e) Autonomic status occurs largely in the Panayiotopoulos syndrome. It
      is included here under the rubric of IGE, although the epilepsy has focal as well
      as generalized features and its nosological position is controversial. Fifty
      percent of seizures in this syndrome could be classified as status epilepticus.
      There is no doubt that convulsive SE can result in cerebral damage. In animal
      models of focal SE, nonconvulsive forms can also result in cerebral damage, but
      cerebral damage is not observed in animal models of absence SE. Similarly,
      cerebral damage seems not to occur in the forms of nonconvulsive SE in human IGE.

PMID- 16302879
TI  - Nonepileptic disorders imitating generalized idiopathic epilepsies.
AB  - Differential diagnosis between epileptic and nonepileptic paroxysmal disorders is
      fundamental not only to allow correct management of patients but also to avoid
      the burden of unnecessary antiepileptic medication. The focus of this chapter is
      limited to imitators of idiopathic generalized epilepsies (IGE) which are
      expressed through myoclonic, tonic-clonic, tonic, atonic, and absence seizures.
      Apparent losses of consciousness and drop attacks also have to be considered.
      Benign myoclonus of early infancy is the main nonepileptic disorder in the
      differential diagnosis of infantile spasms, but is not dealt with here because
      West syndrome is not an IGE. Hyperekplexia, metabolic disorders, hypnagogic
      myoclonus, and disturbed responsiveness caused by the use of drugs are listed in
      Table 1. Other conditions that may imitate more focal epileptic seizures are
      omitted. Benign neonatal sleep myoclonus, apnea and apparent life-threatening
      events in infants, cyanotic and pallid breath-holding spells, syncope, staring
      spells, psychogenic seizures, hyperventilation syndrome, and narcolepsy have been
      selected based on frequency or difficulties in differential diagnosis with the
      intention to cover the most conspicuous imitators of IGE in different ages.

PMID- 16302881
TI  - Idiopathic generalized epilepsies imitating focal epilepsies.
AB  - Classification of epileptic seizures and epilepsy syndromes as either focal or
      generalized is a fundamental and early part in the diagnostic process and is
      generally fairly easily accomplished. However, in patients with idiopathic
      generalized epilepsies, seizure and EEG features may suggest, particularly to the
      unwary, the occurrence of focal rather than generalized seizures.
      Misinterpretation of typical absence seizures as focal seizures, especially as
      temporal lobe seizures and of myoclonic seizures as focal clonic seizures, is a
      relatively common error and focal features during generalized tonic-clonic
      seizures may also be quite common. Sequences of seizures in idiopathic
      generalized epilepsies (such as absences or jerks followed by generalized tonic
      clonic seizures) may also cause confusion. Versive and circling seizures are
      seizure types whose ictal semiology is clearly focal; nevertheless such seizures
      are described in idiopathic generalized epilepsies accompanied by generalized EEG
      discharges. The occurrence of focal EEG abnormalities in certain idiopathic
      generalized epilepsy syndromes is common. This is best known in juvenile
      myoclonic epilepsy.

PMID- 16302880
TI  - Symptomatic epilepsies imitating idiopathic generalized epilepsies.
AB  - The diagnosis of idiopathic generalized epilepsies (IGEs) is not generally
      difficult if one follows the clinical and electroencephalogram (EEG) definitions
      of each subsyndrome that constitutes IGEs. In contrast, symptomatic epilepsies
      develop based on organic brain lesions and are easily diagnosed by the presence
      of developmental delay, neurologic abnormalities, and a characteristic seizure
      and EEG pattern. However, in clinical practice, it is sometimes difficult to
      differentiate IGEs from symptomatic epilepsies, especially when the clinical
      course from the onset of epilepsy is too short to exhibit typical clinical and
      EEG findings of either epilepsy type, or when patients with symptomatic
      epilepsies have atypical features that imitate the clinical characteristics of
      IGEs. The neurodegenerative or metabolic disorders at times start during the
      clinical course with epileptic seizures and later show typical neurologic
      abnormalities. The newly recognized metabolic disorder of glucose transporter
      type 1 deficiency syndrome (Glut-1 DS) may start with myoclonic seizures at an
      age of less than 1 year and imitate benign myoclonic epilepsy in infancy early in
      the clinical course. Progressive myoclonus epilepsies (PMEs) that develop at 1-4
      years of age at times imitate epilepsy with myoclonic-astatic seizures with
      respect to the presence of astatic seizures and an epileptic encephalopathic EEG
      pattern. In addition, young children with focal cortical dysplasia may also have
      similar clinical and EEG patterns, although the latter may become localized after
      treatment. Approximately 15% of patients with juvenile myoclonic epilepsy (JME)
      are resistant to antiepileptic drugs (AEDs) and may require extensive study to
      make a differential diagnosis from symptomatic epilepsies. PMEs that develop
      during adolescence may imitate JME early in the clinical course; however, a
      detailed history and the differentiation between myoclonic seizures and myoclonus
      would help to distinguish both conditions. The diagnosis of IGEs is very
      demanding for patients with atypical features with regard to seizure type, EEG
      findings, and response to appropriate AEDs.

PMID- 16302882
TI  - Use and abuse of EEG in the diagnosis of idiopathic generalized epilepsies.
AB  - This article concentrates on the role of electroencephalograms (EEGs) in the
      diagnosis and management of patients with idiopathic generalized epilepsies
      (IGEs). We review the morphologic and behavioral characteristics of the
      interictal and ictal EEG markers of IGE that should guide recording strategies to
      augment its diagnostic yield, and we attempt to delineate those particular
      features that may be relevant to different IGE syndromes. We also explore the
      electrographic boundaries between IGEs and cryptogenic/symptomatic generalized
      and focal epilepsies, and focal/secondary generalized epilepsies, with particular
      relevance to the phenomena of focal abnormalities and secondary bilateral
      synchrony, commenting on possible diagnostic pitfalls and areas of uncertainty.

PMID- 16302883
TI  - Brain imaging in idiopathic generalized epilepsies.
AB  - While it is generally accepted that there is no neuroimaging abnormality in
      idiopathic generalized epilepsy (IGE), image processing and quantitative magnetic
      resonance imaging (MRI) studies suggest that there may be subtle structural
      abnormalities. Magnetic resonance spectroscopy indicates neuronal dysfunction
      with differing abnormalities in the IGE subsyndromes, and high concentrations of
      glutamate and glutamine have been inferred in the frontal lobes, and low gamma
      aminobutyric acid levels in the occipital lobe. Studies of cerebral blood
      distribution at the time of absences have given complex results. The general
      consensus is of an increase in the thalamus and broad decreases in the neocortex,
      reflecting a suppression of neuronal activity, but with some increases, that may
      indicate focal areas of activation. Positron emission tomography (PET) ligand
      studies with an opioid tracer have inferred neocortical release of endogenous
      opioids at the time of serial absences. In combination with neurophysiological
      methods, PET studies with specific ligands have the potential to clarify the
      functional anatomy and neurochemical circuits that underlie IGE.

PMID- 16302884
TI  - Management guidelines for children with idiopathic generalized epilepsy.
AB  - Most idiopathic generalized epilepsy (IGE) begins in childhood. Clinicians face
      many important management decisions for these children; however the existing
      literature provides little scientific guidance. TIME OF DIAGNOSIS: At the time of
      presentation, it is unclear how accurately IGE seizures and syndromes are
      diagnosed and how consistent are the EEG correlates. Investigations beyond EEG
      are of uncertain value but probably are not needed. Selection of an initial
      antiepileptic drug (AED) is not based on any adequately powered, blinded,
      randomized comparative trials; however, reasonable evidence supports the use of
      valproic acid (VPA), lamotrigine and ethosuccimide as initial treatment for
      childhood absence epilepsy (CAE). Many large case series suggest the value of VPA
      for juvenile myoclonic epilepsy (JME) but the relative value of other, newer AEDs
      has not been established. FIRST YEARS OF TREATMENT: Once AED treatment is
      started, it is difficult to establish that absence seizures are completely
      controlled and the importance of interictal spike-wave discharge remains
      uncertain. The value of restrictions on the child's activities has not been well
      studied; however serious accidents appear to be a justifiable concern in children
      with uncontrolled absence. Assessing the risk from photosensitivity in JME is
      challenging. LENGTH OF TREATMENT: The optimal length of treatment for IGE is
      unclear. There is a high rate of remission in CAE when AEDs are discontinued
      after 1-2 years of seizure freedom; however, long-term remission in CAE occurs in
      only 65%. It is usually assumed that treatment for JME is life long, although
      about 10% appear to have permanent remission in adolescence. Discontinuing AED
      treatment in JME requires a very individual risk assessment. PREPARATION FOR
      ADULT LIFE: Long-term social outcome for children with CAE is often
      unsatisfactory even if the epilepsy remits. The reasons are unclear and
      successful interventions have not been described. Long-term social outcome for
      JME has not been adequately described. CONCLUSIONS: Further research is needed to
      justify the direction of many of the necessary management decisions in the
      diagnosis and treatment of IGE syndromes.

PMID- 16302885
TI  - Best practice guidelines for the management of women with epilepsy.
AB  - Being a woman with epilepsy is not the same as being a man with epilepsy.
      Epilepsy affects sexual development, menstrual cycle, aspects of contraception,
      fertility, and reproduction. MENSTRUAL CYCLE, EPILEPSY, AND FERTILITY: The
      diagnosis of epilepsy and the use of antiepileptic drugs (AEDs) present women of
      childbearing age with many problems; both the disease and its treatment can alter
      the menstrual cycle and fertility. CONTRACEPTION IN EPILEPSY: There are no
      contraindications to the use of nonhormonal methods of contraception in women
      with epilepsy (see Table 3). Nonenzyme-inducing AEDs (valproate sodium,
      benzodiazepines, ethosuximide, and levetiracetam) do not show any interactions
      with the combined oral contraceptive pill. There are interactions between the
      COCP and hepatic microsomal-inducing AEDs (phenytoin, barbiturates,
      carbamazepine, topiramate [doses above 200 mg/day], and oxcarbazepine) and also
      lamotrigine. SEXUALITY: The majority of women with epilepsy appear to have normal
      sex lives, although in some women with epilepsy, both the desire and arousal
      phases may be inhibited. PRECONCEPTION COUNSELING: Preconception counseling
      should be available to all women with epilepsy who are considering pregnancy.
      Women with epilepsy should be aware of a number of issues relating to future
      pregnancy, including methods and consequences of prenatal screening, genetics of
      their seizure disorder, teratogenicity of AEDs, folic acid and vitamin K
      supplements, labor, breast feeding, and childcare. PREGNANCY: The lowest
      effective dose of the most appropriate AED should be used, aiming for monotherapy
      where possible. Recent pregnancy databases have suggested that valproate is
      significantly more teratogenic than carbamazepine, and the combination of
      valproate sodium and lamotrigine is particularly teratogenic. Most pregnancies
      are uneventful in women with epilepsy, and most babies are delivered healthy with
      no increased risk of obstetric complications in women. BREAST FEEDING: All women
      with epilepsy should be encouraged to breastfeed their babies. The AED
      concentration profiled in breast milk follows the plasma concentration curve. The
      total amount of drug transferred to infants via breast milk is usually much
      smaller than the amount transferred via the placenta during pregnancy. However,
      as drug elimination mechanisms are not fully developed in early infancy, repeated
      administration of a drug such as lamotrigine via breast milk may lead to
      accumulation in the infant. THE CARE OF CHILDREN OF MOTHERS WITH EPILEPSY:
      Although there is much anxiety about the possible risks to a child from the
      mother's epilepsy, there is little published evidence. The risk of the child
      being harmed depends on the type of seizure and its severity and frequency, and
      this risk is probably small if time is taken to train mothers and caregivers in
      safety precautions. MENOPAUSE: During menopause, about 40% of women report
      worsening of their seizure disorder, 27% improve, and a third had no change.
      Hormone replacement therapy is significantly associated with an increase in
      seizure frequency during menopause, and this is more likely in women with a
      history of catamenial epilepsy. BONE HEALTH: Women with epilepsy are at increased
      risk of fractures, osteoporosis, and osteomalacia.

PMID- 16302886
TI  - Practical management issues for idiopathic generalized epilepsies.
AB  - The idiopathic generalized epilepsies (IGE) are a group of epilepsies that are
      genetically determined, have no structural or anatomic cause, and usually begin
      early in life. Neurologic examination, intelligence, and imaging studies are
      normal, and EEG shows only epileptiform abnormalities (i.e., no abnormal slow
      activity or evidence for diffuse encephalopathy). In some IGE, the genetic
      substrate has been identified, whereas in most, it remains unknown. Depending on
      the age at onset and predominant seizure type, individual subtypes of IGE
      (syndromes) are defined. However, overall, there are more similarities than there
      are differences among the various subtypes, and the IGE are best viewed as a
      spectrum or continuum of conditions. In general, IGE respond to treatment, with
      80-90% becoming fully controlled. However, not all antiepileptic drugs (AED) are
      equally effective in IGE. Some AED are ill advised because they either do not
      work or exacerbate seizure types other than generalized tonic-clonic (GTC)
      seizures, that is, absence and myoclonic seizures. These include carbamazepine,
      oxcarbazepine, phenytoin, gabapentin, and tiagabine. Their use is the main cause
      of "pseudo-intractability," and at least in the United States where PHT and CBZ
      are the most commonly used AEDs, patients with IGE are often on inadequate
      medications. For patients with clear IGE, the drug of choice is generally
      valproic acid because it effectively controls absence myoclonic seizures and GTC
      seizures. Second-line drugs (when first-line drugs fail or are not tolerated) may
      include benzodiazepines, but the use of second-line drugs is evolving rapidly.
      Some of the newer AEDs are considered broad spectrum, meaning that they work in
      IGE and focal epilepsies, although the evidence is largely preliminary at this
      point. These newer AEDs include lamotrigine, topiramate, levetiracetam, and
      zonisamide.

PMID- 16302887
TI  - Seizure aggravation in idiopathic generalized epilepsies.
AB  - Seizures in the idiopathic generalized epilepsies (IGEs) usually remit completely
      with antiepileptic drugs (AEDs). Occasionally, however, they may be aggravated by
      AEDs. Before attributing exacerbation of seizures to an AED, alternative
      explanations need to be excluded. These include natural fluctuation of seizures,
      irregular compliance, maladjustment to the disease, comorbid illness, and
      development of tolerance. Aggravation may be due to a paradoxical reaction or
      drug-induced encephalopathy, sedative effects, or inappropriate use of a drug;
      and this need to be established, as it will guide management. An important caveat
      is that most data on aggravation of generalized seizures are based on anecdotal
      case reports or case series. Whether considering efficacy or aggravation, the
      interpretation of data from uncontrolled studies and case reports must be treated
      with caution. In practice, despite the fact that clear evidence is lacking, the
      possibility of seizure aggravation must be considered when treating people with
      IGEs. Predictive factors for seizure aggravation in a particular patient with a
      specific drug are yet to be fully defined. It is paramount to classify seizure
      type correctly in all patients. If this is not possible, a broad-spectrum AED
      should be used. Drugs that modulate Na+-channels and GABAergic drugs seem to be
      more prone to aggravating seizures, and therefore are best avoided in the initial
      management of IGE. Further studies are required to elucidate this phenomenon in
      full. It is interesting to speculate that paradoxical responses to AEDs may have
      pharmacogenetic value, serving as tools for a more precise and useful
      characterization of the epilepsies.

PMID- 16302888
TI  - Properties of antiepileptic drugs in the treatment of idiopathic generalized
      epilepsies.
AB  - Although valproate is considered to be the drug of first choice for the treatment
      of idiopathic generalized epilepsies (IGEs), other antiepileptic drugs (AEDs),
      both old (ethosuximide, clobazam, and clonazepam) and new (lamotrigine,
      levetiracetam, topiramate, and zonisamide) are also available. These AEDs do not
      appear to have a common mechanism of action in that both inhibitory gamma
      aminobutyric acid (GABA; e.g., clobazam, clonazepam, and valproate) and
      excitatory glutamate (e.g., lamotrigine and topiramate) mechanisms are involved.
      Ethosuximide primarily acts by blocking T-type voltage-gated calcium channels in
      thalamic neurones while topiramate and zonisamide have multiple mechanisms of
      action. In contrast, levetiracetam is unique in that it may act via a specific
      binding site in the brain. In terms of their pharmacokinetic characteristics, all
      eight AEDs are rapidly absorbed after oral ingestion with peak blood
      concentration being achieved within 1-4 hours. Bioavailability is 100% with the
      exception clonazepam (90%) and topiramate (81-95%). Plasma protein binding is
      variable with valproate (90%), clobazam (85%) and clonazepam (86%) showing
      substantial binding, lamotrigine (55%) and zonisamide (50%) intermediate binding,
      and levetiracetam (0%), ethosuximide (0%) and topiramate (10%) being minimally
      bound. However, the binding by zonisamide is complicated by its binding to
      erythrocytes as well as albumin. All AEDs, with the exception of lamotrigine and
      levetiracetam, undergo elimination as a result of extensive metabolism by hepatic
      cytochrome P450 enzymes, which are highly amenable to induction and inhibition by
      other drugs and therefore susceptible to pharmacokinetic interactions.
      Lamotrigine metabolism is via hepatic glucuronidation, a process that is also
      susceptible to induction and inhibition by concurrent drugs. Levetiracetam is
      minimally metabolized (by hydrolysis in blood), is excreted predominantly
      unchanged in urine, and to date has not been associated with any clinically
      significant pharmacokinetic interactions. Using a semiquantitative
      pharmacokinetic rating system, based on 16 pharmacokinetic characteristics, a
      direct comparison between AEDs is possible. Thus valproic acid, regarded as the
      drug of first choice in the treatment of IGEs, rates lowest with respect to
      favorable pharmacokinetic characteristics, mostly because of its nonlinear
      pharmacokinetics, extensive hepatic metabolism, and its high propensity to
      interact both with other AEDs and non-AEDs. Levetiracetam rates highest with
      topiramate in second place.

PMID- 16302889
TI  - Evidence-based treatment of idiopathic generalized epilepsies with older
      antiepileptic drugs.
AB  - Older antiepileptic drugs continue to play a major role in the treatment of the
      idiopathic generalized epilepsies. Comparative studies of ethosuximide and
      valproate have demonstrated equivalence in the treatment of childhood absence
      epilepsy. Valproate can be regarded as the recommended first-line treatment for
      juvenile myoclonic epilepsy based on case series reports. Studies in patients
      with generalized tonic-clonic seizures have not separated out idiopathic from
      secondary generalized events. Treatment for the other idiopathic generalized
      epilepsy syndromes lacks evidence other than a few case reports and diverse
      expert opinion. Further randomized controlled trials of older antiepileptic drugs
      are recommended to solidify the evidence-based treatment of the idiopathic
      generalized epilepsies.

PMID- 16302890
TI  - Levetiracetam in the treatment of idiopathic generalized epilepsies.
AB  - Since its introduction into clinical practice in 1999, levetiracetam, the S
      enantiomer of piracetam, has rapidly found a secure place, initially in the
      therapy of partial onset seizures and subsequently in the treatment of idiopathic
      generalized epilepsies (IGE). It has many of the properties of an "ideal"
      antiepileptic drug, including rapid absorption, linear pharmokinetics, and sparse
      drug interactions. Tolerabiliy is generally excellent in both adults and
      children, although tiredness is a common dose-limiting adverse effect.
      Occasionally the drug can precipitate behavioral abnormalities, especially in
      patients with learning disability. There is a wide safety margin in overdose. In
      common with most antiepileptic drugs its mode of action remains uncertain.
      Levetiracetam binds to a specific site in the brain, influences intracellular
      calcium currents and reverses negative allosteric modulators of GABA- and glycine
      gated currents in vitro. Its effectiveness has been demonstrated in animal models
      of epilepsy and in clinical trials of partial onset and IGE. Treatment of IGEs
      may be straightforward, with many patients demonstrating an excellent and robust
      response to valproate monotherapy. However, there remains a significant minority
      of patients for whom valproate is unsuitable, including those who experience
      unacceptable adverse effects (e.g., weight gain or hair loss) and women of
      childbearing age in whom the teratogenic potential of valproate is unacceptable.
      Therapeutic response to lamotrigine in this group is often disappointing, and
      many clinicians now are turning to the choice of levetiracetam. Efficacy in
      generalized tonic-clonic seizures and myoclonus is usually apparent and some
      patients experience improvement in typical absences. Experience of combinations
      of levetiracetam with other antiepileptic drugs is limited in IGE and the
      responses are largely anecdotal. In our hands, patients with refractory IGEs may
      respond to combinations of levetiracetam with valproate, lamotrigine, and
      phenobarbital, and adverse effects when they occur are usually limited to
      tiredness. Levetiracetam does not interact with the oral contraceptive pill,
      simplifying treatment in women of childbearing age. Although animal data look
      encouraging, questions over levetiracetam's teratogenic potential and overall
      safety in pregnancy will remain for many years to come.

PMID- 16302891
TI  - Evidence-based treatment of idiopathic generalized epilepsies with new
      antiepileptic drugs.
AB  - With the introduction of over ten new antiepileptic drugs (AEDs) since 1993, the
      hope has been that at least some of these agents would be useful for not just
      partial seizures, but also for the primary generalized seizures of the idiopathic
      generalized epilepsies (IGE). The development of evidence-based treatment
      guidelines in the IGE, however, faces a number of challenges, particularly after
      an antiepileptic drug (AED) receives approval for one indication. The majority of
      patients with IGE are controlled with first-line therapy if appropriately
      selected. Case reports or series typically appear with use in refractory
      patients, but these studies lack the rigor to allow formulation of guidelines.
      Still we are beginning to see some good class I and II data to support use of
      selected second-generation AEDs. It is postulated that lamotrigine (LTG),
      levetiracetam (LEV), topiramate (TPM), and zonisamide (ZSM) may have efficacy for
      a broad spectrum of seizure types including those of IGE. At the present time
      good class I and II evidence exists to support the use of LTG for typical
      absence, LEV for idiopathic myoclonic seizures, and TPM for primary generalized
      tonic-clonic seizures, even though only TPM has FDA approval for primary
      generalized seizures. This article examines the available rigorous evidence that
      can support these uses and also discusses some selected other reports that
      suggest a spectrum of efficacy for these new agents.

PMID- 16302892
TI  - Catheter ablation of long-lasting persistent atrial fibrillation: critical
      structures for termination.
AB  - BACKGROUND: The relative contributions of different atrial regions to the
      maintenance of persistent atrial fibrillation (AF) are not known. METHODS: Sixty
      patients (53 +/- 9 years) undergoing catheter ablation of persistent AF (17 +/-
      27 months) were studied. Ablation was performed in a randomized sequence at
      different left atrial (LA) regions and comprised isolation of the pulmonary veins
      (PV), isolation of other thoracic veins, and atrial tissue ablation targeting all
      regions with rapid or heterogeneous activation or guided by activation mapping.
      Finally, linear ablation at the roof and mitral isthmus was performed if sinus
      rhythm was not restored after addressing the above-mentioned areas. The impact of
      ablation was evaluated by the effect on the fibrillatory cycle length in the
      coronary sinus and appendages at each step. Activation mapping and entrainment
      maneuvers were used to define the mechanisms and locations of intermediate focal
      or macroreentrant atrial tachycardias. RESULTS: AF terminated in 52 patients
      (87%), directly to sinus rhythm in 7 or via the ablation of 1-6 intermediate
      atrial tachycardias (total 87) in 45 patients. This conversion was preceded by
      prolongation of fibrillatory cycle length by 39 +/- 9 msec, with the greatest
      magnitude occurring during ablation at the anterior LA, coronary sinus and PV-LA
      junction. Thirty-eight atrial tachycardias were focal (originating dominantly
      from these same sites), while 49 were macroreentrant (involving the mitral or
      cavotricuspid isthmus or LA roof). Patients without AF termination displayed
      shorter fibrillatory cycles at baseline: 130 +/- 14 vs 156 +/- 23 msec; P =
      0.002. CONCLUSION: Termination of persistent AF can be achieved in 87% of
      patients by catheter ablation. Ablation of the structures annexed to the left
      atrium-the left atrial appendage, coronary sinus, and PVs-have the greatest
      impact on the prolongation of AF cycle length, the conversion of AF to atrial
      tachycardia, and the termination of focal atrial tachycardias.

PMID- 16302893
TI  - Catheter ablation of long-lasting persistent atrial fibrillation: clinical
      outcome and mechanisms of subsequent arrhythmias.
AB  - BACKGROUND: Catheter ablation of atrial fibrillation (AF) is challenging in
      patients with long-standing persistent AF. The clinical outcome and subsequent
      arrhythmia recurrence after using an ablation method targeting multiple left
      atrial sites with the aim of achieving acute AF termination has not been
      characterized. METHODS: Sixty patients (mean age: 53 +/- 9 years) with persistent
      AF (mean duration: 17 +/- 27 months) were prospectively followed after catheter
      ablation. Catheter ablation targeting the following sites was performed in a
      random sequence: (i) electrical isolation of all pulmonary veins (PV); (ii)
      disconnection of other thoracic veins; (iii) atrial ablation at sites possessing
      complex electrical activity, activation gradients, or short cycle lengths.
      Finally, linear ablation of the LA roof and mitral isthmus was performed if sinus
      rhythm was not restored following energy delivery to the above sites. At 1, 3, 6,
      and 12 months after ablation, patients underwent clinical review and 24-hour
      ambulatory ECG monitoring to identify asymptomatic arrhythmia. Repeat mapping and
      catheter ablation was performed in any patient experiencing recurrent atrial
      tachycardia (AT). Clinical success was defined as the absence of any sustained
      atrial arrhythmia. RESULTS: AF terminated during ablation in 52 patients (87%).
      The fluoroscopy and procedural durations were 84 +/- 30 minutes and 264 +/- 77
      minutes, respectively. Three months after ablation, sustained ATs were documented
      in 24 patients (associated with AF in 2). Mapping in 23 patients showed a single
      AT in 7 while multiple ATs were observed in 16. Macroreentry was confirmed to be
      due to gaps in the ablation lines, while focal ATs originated from discrete sites
      or isthmuses near the left atrial appendage, coronary sinus, pulmonary veins, or
      fossa ovalis; these sites were similar to those at which the greatest impact was
      observed on the fibrillatory process during the initial ablation procedure. After
      repeat ablation, at 11 +/- 6 months of follow-up, 57 patients (95%) were in sinus
      rhythm and 3 developed recurrent AF or AT. All patients in sinus rhythm
      demonstrated improved exercise capacity and all but 2 had evidence of atrial
      transport as assessed by Doppler echocardiography (mitral A wave velocity 34 +/-
      17 cm/sec) by 6 months. CONCLUSION: Catheter ablation of long-lasting persistent
      AF associated with acute AF termination achieves medium to long-term restoration
      and maintenance of sinus rhythm in 95% of patients. Arrhythmia recurrence in the
      majority of patients is AT.

PMID- 16302894
TI  - Catheter ablation for persistent atrial fibrillation: are we ready for "prime
      time"?

PMID- 16302895
TI  - Left mitral isthmus ablation associated with PV Isolation: long-term results of a
      prospective randomized study.
AB  - BACKGROUND: The deployment of an ablation line connecting the left inferior PV to
      the mitral annulus (mitral isthmus line [MIL]) enhances the efficacy of pulmonary
      vein disconnection (PVD) in preventing atrial fibrillation (AF) recurrences.
      OBJECTIVES: To investigate the long-term effect of the additional linear lesion
      in a prospective randomized study. METHODS: One hundred and eighty-seven patients
      (37 females, mean age: 55 +/- 11 years) with paroxysmal (126) or persistent (61
      patients) AF, were prospectively randomized into two groups: PVD (group A, 92
      patients) or PVD combined with MIL (group B, 95 patients), performed by means of
      an irrigated-tip ablation catheter. RESULTS: Successful disconnection of all PVs
      was achieved in all patients. A bidirectional block (BB) along the left atrial
      isthmus was obtained in 72 of 95 (76%) patients in group B, most of whom required
      additional RF pulses from within the distal CS. A transient ischemic attack
      occurred in 1 patient of group A, and a cardiac tamponade occurred in 1 patient
      of group B. At 1 year, 53 +/- 5% (group A) and 71 +/- 5% (group B) remained
      arrhythmia free (P = 0.01); subgroup analysis highlights a higher improvement
      among patients with persistent AF (74 +/- 9% vs 36 +/- 9%; P < 0.01) than what
      was observed in paroxysmal AF (76 +/- 6% vs 62 +/- 6%; P < 0.05); antiarrhythmic
      drugs were continued in 56% and 50%, respectively, in groups A and B (P = ns).
      CONCLUSIONS: The addition of mitral isthmus line to the PV disconnection allows a
      significant improvement of sinus rhythm maintenance rate, particularly in
      patients with persistent AF, without the risk for major complications.

PMID- 16302896
TI  - Mitral isthmus ablation for atrial fibrillation.

PMID- 16302897
TI  - Left ventricular-based cardiac stimulation post AV nodal ablation evaluation (the
      PAVE study).
AB  - BACKGROUND: Chronic right ventricular pacing has been reported to promote cardiac
      dyssynchrony. The PAVE trial prospectively compared chronic biventricular pacing
      to right ventricular pacing in patients undergoing ablation of the AV node for
      management of atrial fibrillation with rapid ventricular rates. METHODS AND
      RESULTS: One hundred and eighty-four patients requiring AV node ablation were
      randomized to receive a biventricular pacing system (n = 103) or a right
      ventricular pacing system (n = 81). The study endpoints were change in the 6
      minute hallway walk test, quality of life, and left ventricular ejection
      fraction. Patient characteristics were similar (64% male; age: 69 +/- 10 years,
      ejection fraction: 0.46 +/- 0.16; 83%, NYHA Class II or III). At 6 months
      postablation, patients treated with cardiac resynchronization had a significant
      improvement in 6-minute walk distance, (31%) above baseline (82.9 +/- 94.7 m),
      compared to patients receiving right ventricular pacing, (24%) above baseline
      (61.2 +/- 90.0 m) (P = 0.04). There were no significant differences in the
      quality-of-life parameters. At 6 months postablation, the ejection fraction in
      the biventricular group (0.46 +/- 0.13) was significantly greater in comparison
      to patients receiving right ventricular pacing (0.41 +/- 0.13, P = 0.03).
      Patients with an ejection fraction <or=45% or with NYHA Class II/III symptoms
      receiving a biventricular pacemaker appear to have a greater improvement in 6
      minute walk distance compared to patients with normal systolic function or Class
      I symptoms. CONCLUSION: For patients undergoing AV node ablation for atrial
      fibrillation, biventricular pacing provides a significant improvement in the 6
      minute hallway walk test and ejection fraction compared to right ventricular
      pacing. These beneficial effects of cardiac resynchronization appear to be
      greater in patients with impaired systolic function or with symptomatic heart
      failure.

PMID- 16302898
TI  - PAVEing the way for cardiac resynchronization therapy.

PMID- 16302899
TI  - The impact of cardiac resynchronization therapy on ventricular
      tachycardia/fibrillation: an analysis from the combined Contak-CD and InSync-ICD
      studies.
AB  - OBJECTIVES: To determine the potential influence of cardiac resynchronization
      therapy (CRT) on the frequency and types of ventricular arrhythmia (VA) in
      patients with an indication for the implantable cardioverter-defibrillator (ICD),
      we performed a retrospective electrogram (EGM) analysis of stored VA events from
      the two largest CRT-ICD trials. BACKGROUND: Previous reports suggest that CRT
      might promote polymorphic VT (PVT), while a beneficial effect of CRT on
      ventricular function might reduce the frequency of monomorphic VT (MVT).
      Theoretically, a balanced effect produces no change in overall VA. METHODS: We
      analyzed stored EGMs from patients in the Contak-CD and Insync-ICD studies
      receiving appropriate therapy for VA. EGM inspection distinguishes MVT and PVT
      using morphologic criteria rather than cycle length classification alone.
      RESULTS: Of 1,041 subjects entering the two trials, 880 were randomized CRT (N =
      439) or control (N = 441). We were able to analyze 840 EGMs in 150 patients with
      VA, including 678 MVT episodes and 162 PVT episodes. These events were
      distributed among 68 patients with active CRT (390 MVT vs 111 PVT) and 82
      patients assigned to control (288 MVT compared to 51 PVT). The apparent increase
      in PVT episodes in the CRT group is not significant and can be explained by a
      disproportionate number of episodes in a few patients. We were unable to identify
      clinical variables predictive of PVT during CRT. CONCLUSIONS: CRT is not
      associated with a measurable increase in the incidence of PVT, or in a reduction
      in MVT in the combined InSync-ICD and Contak-CD populations.

PMID- 16302900
TI  - Outcomes after cardiac perforation during radiofrequency ablation of the atrium.
AB  - BACKGROUND: Perforation during catheter procedures in either the atrium or
      ventricle is relatively uncommon, but potentially fatal if tamponade ensues. This
      study analyzes the occurrence and outcomes of cardiac perforation during catheter
      based radiofrequency ablation procedures in the left atrium. METHODS: All
      patients with a periprocedure perforation who have undergone radiofrequency
      ablation for atrial fibrillation (AF) or tachycardia were included. RESULTS: Of
      632 procedures performed from January 1999 to October 2004, 15 (2.4%) were
      complicated by perforation requiring pericardiocentesis. The perforation site was
      left atrium in 9 (60.0%), right atrium in 1 (6.7%), and right ventricle in 5
      (33.3%). Intracardiac echocardiography was used in 13 (86.7%) and revealed an
      effusion before overt instability in 11 (73.3%). Thirteen (86.7%) patients
      developed a blood pressure <60 mmHg. The pressure stabilized in all patients
      after pericardiocentesis (hypotension to intervention: 10.1 +/- 5.1 minutes). The
      total blood volume removed was 848 +/- 880 mL (left atrium/right atrium: 1,074 +/
      1,002 vs right ventricle: 396 +/- 266, P = 0.168). Two patients required surgery
      to close left atrium dome perforations. The ablation was completed in 7 (46.7%)
      patients. Ten (66.7%) later developed early reoccurrence of AF. All patients were
      neurologically intact at hospital discharge. During a 1.5 +/- 1.1 year follow-up,
      AF was eliminated (n = 4) or controlled (n = 1) in 5 (71.4%) patients with
      complete procedures, and 2 (20.0%) patients underwent successful repeat ablation.
      CONCLUSION: The incidence of perforation during ablation of the left atrium is
      low. Most perforations occur in the left atrium; however, few require surgical
      closure. Although less than with uncomplicated procedures, the majority of
      patients with complete ablations achieve long-term elimination of AF.

PMID- 16302901
TI  - Percutaneous pulmonary vein stenting for the treatment of severe stenosis after
      pulmonary vein isolation.
AB  - INTRODUCTION: Pulmonary vein stenosis (PVS) is a potential complication of
      pulmonary vein isolation (PVI) using radiofrequency energy. The aim of our study
      was the evaluation of the severity and long-term outcome of primary angioplasty
      and angioplasty with pulmonary vein stenting for PVS. METHODS AND RESULTS: Twelve
      patients with 15 PVS (greater than 70% stenosis) were prospectively evaluated.
      Primary dilation of the stenosis was performed because of clinical symptoms (10
      patients) and/or the lung perfusion scans showed a significant perfusion defect
      (11 patients). Magnetic resonance imaging and lung perfusion scans performed
      before, directly after, during 3-month, and 6-month follow-up. In the stenting
      group additional multislice CT-scans directly after, during 6-month, and 12-month
      follow-up were performed. Within 2 months after primary balloon angioplasty, the
      PV size parameters were significantly reduced (P < 0.001) with recurrence of PVS
      in 11 of 15 PVs (73%). Pulmonary vein stenting in 8 patients and 11 PVs resulted
      in no vein stenosis during 12-month follow-up. Normalization of lung perfusion
      was noted in 8 of 12 patients. We observed 2 patients with hemoptysis during PV
      dilation, as severe complications with potential life-threatening character.
      CONCLUSION: PVS stenting seems to be superior to balloon angioplasty and
      effective at least over a period of 12 months in treating acquired PVS after
      pulmonary vein isolation.

PMID- 16302902
TI  - Dietary fish oil protects against stretch-induced vulnerability to atrial
      fibrillation in a rabbit model.
AB  - INTRODUCTION: Dietary fish oil is thought to reduce sudden cardiac death by
      suppressing ventricular arrhythmias but little is known about its impact on
      atrial arrhythmias. We examined the effect of dietary fish oil on the rabbit
      model of stretch-induced vulnerability to atrial fibrillation (AF). METHODS AND
      RESULTS: Six-week-old rabbits were fed standard rabbit pellets supplemented with
      5% tuna fish oil (n = 6) or supplemented with 5% sunflower oil (n = 6) for 12
      weeks. Six rabbits raised on the standard diet were used as controls. In
      Langendorff-perfused hearts intraatrial pressures were increased in a stepwise
      manner and rapid burst pacing applied to induce AF at increasing intraatrial
      pressures until AF was sustained (>1 minute). Atrial refractory periods were
      recorded at each pressure. Increased atrial pressure resulted in a reduction in
      atrial refractory period and a propensity for induction of sustained AF. Higher
      pressures were needed to induce and sustain AF in the fish oil group compared
      with the sunflower oil and control groups. The stretch-induced drop in refractory
      period was also less marked in the fish oil group. Red blood cell, atrial, and
      ventricular omega-3 fatty acid levels were significantly higher in the fish oil
      group. The ratio of atrial n-6/n-3 polyunsaturated fatty acids was 13 +/- 0.9
      with sunflower oil and 1.5 +/- 0.01 with fish oil (P < 0.001). CONCLUSIONS:
      Incorporation of dietary omega-3 fatty acids into atrial tissue reduces stretch
      induced susceptibility to AF.

PMID- 16302903
TI  - Drugs, ablation, denervation... and now fish oil: the global war on AF.

PMID- 16302904
TI  - Evidence that activation following failed defibrillation is not caused by
      triggered activity.
AB  - BACKGROUND: Earliest postshock activation following failed defibrillation shocks
      slightly lower than the defibrillation threshold (DFT) in large animals appears
      to arise from a focus. We tested the hypothesis that these foci are caused by
      early or delayed afterdepolarizations (EADs or DADs) by performing epicardial
      electrical mapping and giving the EAD inhibitor pinacidil or the DAD inhibitor
      flunarizine to see if the foci were extinguished or altered in timing or
      location. METHODS AND RESULTS: A sock containing 504 electrodes was placed over
      the entire ventricular epicardium of 12 open-chested pigs. After the DFT was
      determined and additional shocks given, pinacidil was administered to 6 pigs and
      flunarizine to 6 pigs. Then, the DFT was again determined and additional shocks
      were given. Pinacidil significantly shortened the effective refractory period
      (ERP) (162 +/- 16 vs 130 +/- 28 msec) and action potential duration (APD(90))
      (179 +/- 6 vs 149 +/- 19 msec) and significantly increased the peak frequency of
      the power spectrum of a left ventricle (LV) electrode during ventricular
      fibrillation (VF) (9.3 +/- 0.6 vs 10.5 +/- 1.0 Hz), while flunarizine did not
      significantly alter the ERP (162 +/- 8 vs 167 +/- 18 msec) or APD(90) (187 +/- 12
      vs 191 +/- 20) but significantly reduced the peak frequency (9.2 +/- 0.5 vs 7.5
      +/- 1.0 Hz). These findings suggest the drugs had their expected
      electrophysiological effects. However, the DFT was not significantly changed by
      either drug. Following the same strength shock 10% below the predrug DFT,
      earliest postshock activation arose in a focal epicardial pattern from the
      anterior-apical LV both before and after the drugs. The time from the shock until
      the appearance of this activation was not significantly different before and
      after either drug. CONCLUSION: The lack of change in DFT as well as the lack of
      change in the incidence, location, and timing of the postshock focus with sub-DFT
      strength shocks before and after pinacidil and flunarizine provide evidence that
      these foci are not caused by triggered activity.

PMID- 16302905
TI  - The puzzle of defibrillation: putting the pieces together.

PMID- 16302907
TI  - Preservation of sinus node function by Angiotensin converting enzyme inhibitors.

PMID- 16302906
TI  - Enalapril preserves sinus node function in a canine atrial fibrillation model
      induced by rapid atrial pacing.
AB  - METHODS AND RESULTS: Seventeen beagles were pretreated with either placebo (group
      I, n = 9) or enalapril 1 mg/kg/day (group II, n = 8) and paced at 500/min from
      the right atrial appendage for 4 weeks. Every week, corrected sinus node recovery
      time (CSNRT) and sinus cycle length (SCL) were measured. Quantitative analysis of
      interstitial fibrosis (IF) and adipose tissue (AT) in the SN was performed with
      Masson's trichrome stain, and apoptosis of the sinus nodal cells were detected
      with terminal deoxynucleotidyl transferase nick end-labeling. In group I, rapid
      atrial pacing prolonged both CSNRT and SCL. After 4 weeks of pacing, CSNRT and
      SCL were significantly shorter in group II (CSNRT, 410 +/- 37 msec; SCL, 426 +/-
      34 msec) than in group I (CSNRT, 717 +/- 52 msec, P < 0.005; SCL, 568 +/- 73
      msec, P < 0.05). Both IF and AT of the SN were greater in group I (IF, 9.7 +/-
      1.9%; AT, 32.6 +/- 5.9%) than in seven sham dogs (IF, 2.4 +/- 0.9%, P < 0.05; AT,
      4.0 +/- 1.7%, P < 0.05) and in group II dogs (IF, 4.0 +/- 2.0%, P < 0.05; AT, 4.0
      +/- 1.7%, P < 0.05). End-labeling assay was positive in three of nine dogs in
      group I, but negative in group II and sham dogs. CONCLUSIONS: Rapid atrial pacing
      impaired SN function through IF and AT of the SN. Enalapril prevented these
      pacing-induced degenerative changes and improved SN function.

PMID- 16302908
TI  - Comparison of cryothermia and radiofrequency current in safety and efficacy of
      catheter ablation within the canine coronary sinus close to the left circumflex
      coronary artery.
AB  - INTRODUCTION: A canine model was used to compare cryoablation and radiofrequency
      ablation (RFA) within the coronary sinus (CS) in the ability to create a
      transmural CS myocardial (Trans-CSM) lesion and risk of coronary artery stenosis.
      METHODS: After CS and left circumflex (LCx) coronary angiography, an
      intravascular ultrasound (IVUS) probe was placed in LCx in 29 dogs. An irrigated
      RFA catheter (8 dogs) or N(2)O cryoablation catheter (21 dogs) was inserted into
      the CS and positioned within 2 mm of LCx, confirmed by IVUS. RF (30-50W) was
      applied for 60 seconds at 10 CS sites. Cryoablation (-75 degrees C) was performed
      with one (n = 7) or two (n = 14) 4-minute applications. Dogs were sacrificed at 1
      week (8 RFA and 13 cryoablation) or 3 months (8 cryoablation). RESULTS: During
      RFA, IVUS showed wall thickening and LCx narrowing in 9 of 10 sites. Angiography
      at 5-minute post-RFA identified LCx narrowing (25-90%) at 6 of 10 sites and 25
      75% narrowing at 4 of 9 sites at 1-week post-RFA. During cryoablation, IVUS
      showed reversible ice ball compression of LCx, and no LCx narrowing by
      angiography at 5 minutes, 1 week, or 3 months. Histology showed Trans-CSM lesion
      at 10 of 10 RFA sites and 20 of 21 cryoablation sites. RFA produced LCx medial
      necrosis at 7 of 10 sites, involving 20-50%(median 32.5%) of LCx circumference
      with loss of intima at 5 of 7 sites. Single and twice 4-minute cryoablation
      produced LCx medial necrosis at 2 of 7 and 8 of 14 sites (5-40%, median 25%
      circumference). Intima was preserved at 1 week (13/13) with minor proliferation
      (without narrowing) at 2 of 8 sites at 3 months. CONCLUSIONS: Cryoablation in CS
      within 2 mm of LCx produces Trans-CSM lesions similar to RFA with lower risk of
      LCx stenosis than RFA.

PMID- 16302909
TI  - The mechanism of atrial antiarrhythmic action of RSD1235.
AB  - INTRODUCTION: RSD1235 is a novel drug recently shown to convert AF rapidly and
      safely in patients.(1) Its mechanism of action has been investigated in a rat
      model of ischemic arrhythmia, along with changes in action potential (AP)
      morphology in isolated rat ventricular myocytes and effects on cloned channels.
      METHODS AND RESULTS: Ischemic arrhythmias were inhibited with an ED50 of 1.5
      micromol/kg/min, and repolarization times increased with non-significant effects
      on PR and QRS durations. AP prolongation was observed in rat myocytes at low
      doses, with plateau elevation and a reduction in the AP overshoot at higher
      doses. RSD1235 showed selectivity for voltage-gated K+ channels with IC50 values
      of 13 microM on hKv1.5 (1 Hz) versus 38 and 30 microM on Kv4.2 and Kv4.3,
      respectively, and 21 microM on hERG channels. RSD1235 did not block IK1 (IC50 > 1
      mM) nor ICa,L (IC50= 220 microM) at 1 Hz in guinea pig ventricular myocytes (n =
      4-5). The drug displayed mild (IC50= 43 microM at 1 Hz) open-channel blockade of
      Nav1.5 with rapid recovery kinetics after rate reduction (10-->1 Hz, 75% recovery
      with tau= 320 msec). Nav1.5 blocking potency increased with stimulus frequency
      from an IC50= 40 microM at 0.25 Hz, to an IC50= 9 microM at 20 Hz, and with
      depolarization increasing from 107 microM at -120 mV to 31 microM at -60 mV (1
      Hz). CONCLUSIONS: These data suggest that RSD1235's clinical selectivity and AF
      conversion efficacy result from block of potassium channels combined with
      frequency- and voltage-dependent block of INa.

PMID- 16302910
TI  - Epicardial idiopathic ventricular tachycardia originating within the left main
      coronary artery ostium area: identification using the LocaLisa nonfluoroscopic
      catheter navigation system.
AB  - Idiopathic ventricular tachycardia (IVT) in patients without structural heart
      disease commonly arises from the right or left outflow tracts, but there remain
      arrhythmias that can only be ablated by an epicardial approach. We report a case
      of an epicardial ventricular tachycardia originating within the left main
      coronary artery ostium area, as identified using the LocaLisa nonfluoroscopic
      catheter navigation system. Due to the high risk of coronary artery thrombosis,
      ventricular tachycardia was successfully ablated by a transthoracic surgical
      approach using cryoenergy. Ventricular ectopy disappeared and ventricular
      tachycardia did not recur during long-term follow-up.

PMID- 16302911
TI  - Sinus node injury as a complication of superior vena cava isolation.
AB  - We report a case with SVC ectopy initiating AF; the origin and breakout point of
      the sinus node was inside the SVC, and the SVC ectopy was conducted through the
      same path as the sinus node activation to depolarize the right atrium. Injury to
      the sinus node happened after successful isolation of SVC.

PMID- 16302912
TI  - Human histopathology of electroanatomic mapping after cooled-tip radiofrequency
      ablation to treat ventricular tachycardia in remote myocardial infarction.
AB  - INTRODUCTION: Catheter ablation of ventricular tachycardia (VT) in remote
      myocardial infarction (MI) often requires excessive mapping procedures.
      Documentation of the electrical substrate via electrogram amplitude may help to
      identify regions of altered myocardium resembling exit areas of reentrant VTs.
      METHODS AND RESULTS: A patient with multiple symptomatic monomorphic VTs
      (biventricular ICD, remote MI) underwent electroanatomic substrate mapping
      (CARTOtrade mark) for VT ablation. Regions of scar (bipolar electrogram
      amplitudes <or=0.5 mV), normal myocardium (>or=1.5 mV), and "altered" myocardium
      (0.5-1.5 mV) were identified. Ablation was directed to regions with "altered"
      myocardium based on pace map correlation. After ablation the clinical VT did not
      reoccur. The patient died due to worsening of heart failure 7 days afterward.
      During postmortal evaluation specified sites of electroanatomic mapping were
      correlated to histopathological findings. Annotated scar areas were documented to
      consist of areas with massive fibrosis (>or=80% of mural composition). Ablations
      were found to span through regions with intermediate fibrosis (21-79%) mapped as
      "altered" myocardium. Ablation produced transmural coagulation necrosis of mesh
      like fibrotic tissue with interspersed remnants of myocardial cells up to a
      maximum depth of 7.0 mm. Subendocardial intramural bleedings were universal
      findings 7 days after ablation. CONCLUSIONS: Electroanatomic substrate mapping
      for VT ablation sufficiently identified regions of scar and normal myocardium.
      Regions with bipolar electrogram amplitudes between 0.5 and 1.5 mV were found to
      correlate to areas of "intermediate" fibrosis (21-79%) with only remnant strands
      of myocardial cells and were identified as target region for ablation. Cooled-tip
      endocardial radiofrequency ablation lead to transmural coagulation necrosis up to
      a depth of 7.0 mm.

PMID- 16302913
TI  - Alternating R-R intervals during broad-complex tachycardia: what is the
      mechanism?

PMID- 16302914
TI  - Arrhythmias after cell transplantation for myocardial regeneration: natural
      history or result of the intervention?

PMID- 16302915
TI  - Is Wolff-Parkinson-White syndrome a genetic disease?
AB  - Family studies, and more recent molecular genetic investigations, indicate that
      the Wolff-Parkinson-White (WPW) syndrome and associated preexcitation disorders
      can have a substantial genetic component. Because preexcitation disorders are
      sometimes inherited as single gene disorders, key mechanistic insights can be
      gained that are expected to be relevant also to the more common multifactorial
      forms of these traits. Potentially, such insights will inform the future
      management of these conditions. Where WPW is inherited as a familial trait, with
      or without associated cardiac defects or a systemic syndrome, there are clinical
      genetic ramifications that are already of practical importance.

PMID- 16302917
TI  - Quantitative assessment on microvolt T-wave alternans (MTWA) in 204 consecutive
      patients with congestive heart failure.

PMID- 16302919
TI  - Association of matrix metalloproteinase-1 promoter polymorphism with generalized
      aggressive periodontitis in a Chinese population.
AB  - BACKGROUND: A single nucleotide polymorphism in the promoter region of -1607 bp
      of the human matrix metalloproteinase-1 (MMP-1) gene has been found to be
      associated with an increased risk of various inflammatory diseases and cancer
      metastasis. OBJECTIVES: The present study aimed to examine the distribution of
      MMP-1 genotypes in a group of Chinese subjects with generalized aggressive
      periodontitis and a group of periodontally healthy subjects, and to evaluate the
      possible association of the MMP-1 promoter polymorphism with aggressive
      periodontitis. METHODS: Genomic DNA was obtained from whole blood samples in 40
      Chinese subjects with generalized aggressive periodontitis and 52 periodontally
      healthy subjects as controls. MMP-1 promoter fragment was amplified by polymerase
      chain reaction, and the polymorphisms were analyzed by restriction endonuclease
      cleavage. The alleles were detected by polyacrylamide gel electrophoresis and
      visualized with ethidium bromide. RESULTS: The detection frequency of 2G allele
      was significantly higher in the subjects with generalized aggressive
      periodontitis (68.7%) than in the control subjects (49%) (p < 0.01). The genotype
      of 2G/2G was found in 52.5% of the patients, which was significantly greater than
      that of control subjects (23.1%) (p < 0.05). CONCLUSION: The present study
      suggests that a single nucleotide polymorphism in the MMP-1 promoter region of 
      1607 bp may be associated with generalized aggressive periodontitis in Chinese
      population.

PMID- 16302920
TI  - Retinoic acid is a potential negative regulator for differentiation of human
      periodontal ligament cells.
AB  - BACKGROUND AND OBJECTIVES: Retinoic acid (RA) exerts a wide variety of effects on
      development, cellular differentiation and homeostasis in various tissues.
      However, little is known about the effects of RA on the differentiation of
      periodontal ligament cells. In this study, we investigated whether RA can affect
      the dexamethasone-induced differentiation of periodontal ligament cells. METHODS
      AND RESULTS: Human periodontal ligament cells were differentiated via culturing
      in the presence of dexamethasone, ascorbic acid, and beta-glycerophosphate for
      mineralized nodule formation, as characterized by von Kossa staining. Continuous
      treatment with all-trans-RA inhibited the mineralization in a dose-dependent
      manner, with complete inhibition over 1 microm RA. Other RA analogs, 9-cis-RA and
      13-cis-RA, were also effective. Furthermore, addition of RA for just the first 4
      days completely inhibited the mineralization; however, as RA was added at later
      stages of culture, the inhibitory effect was diminished, suggesting that RA had a
      phase-dependent inhibition of mineralization. RA receptor (RAR)-alpha agonist (AM
      580), but not retinoid X receptor agonist (methoprene acid), inhibited the
      mineralization, and reverse transcription-polymerase chain reaction analysis
      revealed that RAR-alpha was expressed on the cells, suggesting that RAR-alpha was
      involved in the inhibitory mechanism. This inhibition was accompanied by
      inhibition of alkaline phosphatase activity; however, neither expression of
      platelet-derived growth factor (PDGF) receptor-alpha, PDGF receptor-beta, or
      epidermal growth factor (EGF) receptor, nor phosphorylation of extracellular
      signal-regulated kinases triggered by PDGF-ascorbic acid or PDGF-BB was changed,
      as assessed by flow cytometry or western blot analyses. CONCLUSIONS: These
      findings suggest that RA is a potential negative regulator for differentiation of
      human periodontal ligament cells.

PMID- 16302921
TI  - Bone response to different strength orthodontic forces in animals with
      periodontitis.
AB  - BACKGROUND: Occlusal alterations resulting from tooth movements caused by
      periodontitis-related bone loss are often corrected with orthodontic treatments.
      Although the outcome is usually satisfactory, a quantitative histomorphometric
      study of bone response would contribute to improving treatment planning and
      optimizing results. METHODS AND RESULTS: This study is a histomorphometric
      analysis of alveolar bone response to 51 and 75-g orthodontic forces applied to
      rat molars subjected to experimental periodontitis by placing a ligature around
      the neck of the molar during 48 h. The orthodontic device consisted of two bands
      with a tube welded to their palatine aspect, through which the arms of a
      helicoidal spring were threaded so as to exert force toward palatine. The device
      was placed immediately and 48 h after removing the ligatures. When applied 48 h
      post-removal of the ligature, both orthodontic forces caused an increase in bone
      volume in the periodontitis group. CONCLUSIONS: Our study shows that application
      of orthodontic forces once periodontal infection has been controlled contributes
      to increasing alveolar bone volume, consequently improving bone quality.

PMID- 16302922
TI  - Genetic relatedness of oral yeasts within and between patients with marginal
      periodontitis and subjects with oral health.
AB  - BACKGROUND: Yeasts are found in periodontal pockets at a frequency of 15-21%.
      However, the genetic relatedness of oral yeasts within and between patients with
      marginal periodontitis is not clear. OBJECTIVES: Assay genetic relatedness of
      oral yeasts from marginal periodontitis patients and oral health subjects, as
      well as genetic relatedness of yeasts from different oral sites in these two
      groups of participants. MATERIAL AND METHODS: Yeast isolates were collected from
      23 marginal periodontitis patients and 19 oral health subjects. Random amplified
      polymorphic DNA (RAPD) fingerprinting and the Dendron computer-assisted program
      for gel analyses were applied for estimation of genetic relatedness of yeasts.
      RESULTS: The similarity coefficient (S(AB)) of the marginal periodontitis group
      ranged from 0.49 to 1.00 with an average of 0.64 +/- 0.11, whereas the S(AB) of
      the oral health group ranged from 0.62 to 1.00 with an average of 0.72 +/- 0.07.
      Three genetic clusters and 73 genotypes were obtained from the marginal
      periodontitis group, whereas three genetic clusters and 55 genotypes were found
      in the oral health group. In the pooled dendrogram, 57% of the yeast isolates and
      the type strain of Candida albicans fell in a major cluster V. There were no
      significant differences between the frequencies of clusters from the different
      oral sites within the two participant groups. CONCLUSIONS: Genetically
      heterogeneous yeasts were found in the oral cavities of marginal periodontitis
      patients and oral health subjects. Similar genetic clustering patterns were
      obtained from the yeasts of the two groups, with cluster V being most
      predominant. Yeasts of the marginal periodontitis group were more genetically
      diverse than yeasts of the oral health group, and some yeasts of the marginal
      periodontitis group exhibited unique genetic patterns. There was no clear
      association between yeast genetic clusters and oral sites in the two participant
      groups.

PMID- 16302923
TI  - The correlation between the bone probing, radiographic and histometric
      measurements of bone level after regenerative surgery.
AB  - BACKGROUND AND OBJECTIVE: The most accurate method of assessing bone level is to
      elevate the flap and measure the bone level directly. However, this method causes
      discomfort to the patient and can damage the tissues. Therefore, many studies
      have been conducted to find an alternative method that can be used to assess the
      bone level clinically with accuracy and reliability. In the present study, we
      evaluated the clinical reliability and accuracy of bone probing and radiographic
      measurements, by comparing the bone levels obtained by both of these measurement
      techniques with the histometrically confirmed bone levels, after four different
      kinds of regenerative therapy. METHODS: Twenty-four intrabony defects (4 x 4 mm
      one-wall intrabony defects) were surgically created bilaterally in the mandibular
      second and fourth premolars of six beagle dogs. The control group underwent a
      conventional flap operation. The graft group was treated with calcium phosphate
      glass only, the guided tissue regeneration group was treated with guided tissue
      regeneration only, and the graft + guided tissue regeneration group was treated
      with calcium phosphate glass and guided tissue regeneration. Bone probing and
      radiographic measurements were performed to assess the bone level 8 weeks after
      the operation and then the subjects were killed to perform the histometric
      measurements. The correlation between the bone probing depths and the histometric
      bone levels, and that between the radiographic bone levels and the histometric
      bone levels were analyzed by Spearman's rank correlation analysis. The
      statistical significance with respect to the type of regenerative therapy was
      analyzed by the Kruskal-Wallis test. RESULTS: The difference between the bone
      probing depth and the histometric bone level measurements was 0.14, and that
      between the radiographic bone level and histometric bone level was 0.6. The
      coefficient of correlation between the bone probing depth and the histometric
      bone level was 0.90, and that between the radiographic bone level and the
      histometric bone level was 0.73. The type of regenerative therapy had no
      significant effect on the difference between the histometric bone level and the
      other measurements. CONCLUSION: The results of the present study suggest that the
      bone probing measurement may be a reliable method for the assessment of the
      actual bone level following any type of periodontal regenerative therapy.

PMID- 16302924
TI  - Suppression of lipopolysaccharide-induced cytokine production of gingival
      fibroblasts by a soybean, Kunitz trypsin inhibitor.
AB  - BACKGROUND: Human bikunin, a Kunitz-type trypsin inhibitor, inhibits inflammation
      by down-regulating the expression of proinflammatory cytokines such as tumor
      necrosis factor-alpha (TNF-alpha) in tumor cells and inflammatory cells.
      OBJECTIVES: We analyzed the effect of a soybean-derived Kunitz trypsin inhibitor
      (KTI) on TNF-alpha production in human gingival fibroblasts stimulated by
      lipopolysaccharide (LPS), an inflammatory inducer. MATERIAL AND METHODS: Mitogen
      activated protein kinase (MAPK) activation and cytokine levels were monitored
      using western blot and a specific enzyme-linked immunosorbent assay (ELISA).
      RESULTS: Here, we show (i) a soybean KTI abrogates LPS-induced up-regulation of
      TNF-alpha mRNA and protein expression in a dose-dependent manner in gingival
      fibroblasts, (ii) KTI also blocks the induction of TNF-alpha target molecules
      interleukin-1beta (IL-1beta) and IL-6 proteins, (iii) inhibition by KTI of TNF
      alpha induction correlates with the suppressive capacity of extracellular signal
      regulated kinase 1/2 (ERK1/2) and p38 signaling pathways, implicating repressed
      ERK1/2 and p38 signalings in the inhibition, and (iv) pretreatment of cells with
      KTI blocked LPS-induced nuclear factor kappaB (NFkappaB) activation. CONCLUSION:
      Our results indicate that KTI inhibits LPS-induced up-regulation of cytokine
      expression possibly through suppression of ERK1/2 and p38 kinase-mediated
      NFkappaB activation. These findings may identify anti-inflammatory properties of
      KTI at the level of gingival fibroblasts and may be relevant to the use of KTI in
      modulating inflammation, including periodontal disease.

PMID- 16302925
TI  - Inhibitory effects of a super pulsed carbon dioxide laser at low energy density
      on periodontopathic bacteria and lipopolysaccharide in vitro.
AB  - OBJECTIVE AND BACKGROUND: Previous studies have described the effect of
      irradiation by a carbon dioxide (CO2) laser at high energy density on oral
      bacteria, and various side-effects have also been observed. However, no published
      studies have examined the effect of irradiation by a CO2 laser at low energy
      density on oral bacteria. The purpose of this study was to investigate the
      effects of super pulsed CO2 laser irradiation on periodontopathic bacteria and
      lipopolysaccharide (LPS). METHODS: Bacterial suspensions of two species of
      periodontopathic bacteria received laser irradiation at energy densities of 0
      12.5 J/cm2. The suspensions were then spread over agar plates and incubated
      anaerobically. The bactericidal effects were evaluated based on colony formation.
      Samples of LPS were laser-irradiated at energy densities of 0-12.5 J/cm2. The
      biological activity was measured, and LPS was analyzed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: The irradiation at low
      energy densities of 7.5 and 12.5 J/cm2 killed more than 99.9 and 99.999% of
      Porphyromonas gingivalis and more than 99% of Actinobacillus
      actinomycetemcomitans was sterilized by the irradiation at 7.5 J/cm2. LPS
      biological activity was significantly decreased by laser irradiation at energy
      densities of more than 7.5 J/cm2 (p < 0.05), and the components of LPS analyzed
      by SDS-PAGE was diminished non-specifically. CONCLUSION: The results indicate
      that CO2 laser irradiation at low power is capable of bactericidal effect on
      periodontopathic bacteria and decreasing LPS activity.

PMID- 16302926
TI  - Expression of human beta-defensin-3 in gingival epithelia.
AB  - OBJECTIVE: This study aimed to investigate the expression patterns of the newly
      discovered human beta-defensin-3 (hBD-3) in human gingiva. BACKGROUND: Human beta
      defensins (hBDs) are a group of small, broad-spectrum, cationic antimicrobial
      peptides. Our recent study showed that the expression levels of hBD-1 and 2
      peptides were associated with periodontal conditions. METHODS: A total of 49
      gingival biopsies were collected, including 33 samples from 21 patients with
      chronic periodontitis and 16 samples from 16 periodontally healthy subjects. The
      expression of hBD-3 was detected by immunohistochemistry and in situ
      hybridization. Double staining was undertaken to identify hBD-3 peptide-positive
      cells, using CD-1a and cytokeratin 20 as markers for Langerhans cells and Merkel
      cells, respectively. RESULTS: hBD-3 peptide was detected in 88% of the samples,
      which was confined to the gingival epithelia. In healthy control subjects, hBD-3
      peptide was more frequently detected in the basal layer as compared to the
      patients (53% vs. 18%, p < 0.05). In patients, hBD-3 expression extended from the
      basal layer to the spinous layers (82%), in which hBD-3 was confined to the basal
      and deep spinous layers in clinically healthy tissues from patients, whereas it
      extended to the superficial spinous layers in pocket tissues from patients (0%
      vs. 50%, p < 0.05). In both groups, hBD-3 peptide was expressed not only in
      gingival keratinocytes, but also in Langerhans cells and Merkel cells. hBD-3
      transcripts were detected in 90% of the samples and they were confined to the
      basal and/or suprabasal layers of gingival epithelia. CONCLUSIONS: This study
      shows that hBD-3 is frequently expressed in gingival epithelia. The appropriate
      expression of hBD-3 peptide may contribute to the maintenance of periodontal
      homeostasis, possibly through its antimicrobial effect and promotion of adaptive
      immune responses.

PMID- 16302927
TI  - The distribution of Tannerella forsythia in an adolescent and adult population.
AB  - BACKGROUND: The fact that Tannerella forsythia, an important periopathogen, is
      difficult to cultivate from mixed infections has impeded precise estimates of its
      distribution within a given population. In order to discern T. forsythia alone
      from the mixed infection of plaque, the use of sensitive 16S ribosomal RNA based
      polymerase chain reaction (PCR) detection is necessary. OBJECTIVES: The aim of
      the present study was to determine the distribution of T. forsythia in an adult
      and in an adolescent population. MATERIAL AND METHODS: Subgingival plaque samples
      were obtained from 498 Australian adults and from 228 adolescent subjects from
      Manchester, UK. Tannerella forsythia was detected using PCR and confirmed by
      restriction analysis. Semi-quantitation of the organisms was carried out using
      two specific primers of differing sensitivities. RESULTS: In the adolescent
      population, 25% were found to carry T. forsythia, albeit in relatively low
      numbers. In the adult population, a total of 37.8% and 11% were found to carry
      the organism with primer 2 and primer 1, respectively, suggesting that around 27%
      had between 10(3) and 10(7) organisms. Although there was an apparent increased
      proportion of T. forsythia positive subjects in those aged > or = 50 years, this
      was not statistical significant. However, T. forsythia positive male smokers
      showed increased disease severity compared with T. forsythia negative subjects.
      CONCLUSION: This study has shown that at least 25% of the adolescent population
      carry low numbers of T. forsythia, whereas at least 37% of adults carry the
      organism, with some 11% having relatively high numbers. The relationship between
      T. forsythia and disease progression in these populations, however, remains to be
      determined.

PMID- 16302928
TI  - In vitro cell-type specific biological response of human periodontally related
      cells to platelet-rich plasma.
AB  - OBJECTIVES: Platelet-rich plasma is a blood-derived fraction containing high
      concentrations of platelets and growth factors. Applied in the form of a gel on
      surgical wounds, it is able to stimulate hard and soft tissue repair and has been
      proposed for use in the field of periodontal regeneration. However to date,
      little is known about the biological interactions between platelet-rich plasma
      and periodontally related cells. In this study, we investigated the effects
      between platelet-rich plasma and cell populations involved in periodontal
      regeneration, namely primary human periodontal ligament cells, gingival
      fibroblasts and keratinocytes. MATERIAL AND METHODS: The proliferation of human
      periodontal ligament cells, gingival fibroblasts and keratinocytes by
      [3H]thymidine incorporation was assessed. The alkaline phosphatase activity and
      type I collagen levels of human periodontal ligament cells were also evaluated by
      a spectrophotometric assay and western blot analysis, respectively. RESULTS:
      Incubation of human periodontal ligament cells with platelet-rich plasma resulted
      in time-dependent growth stimulation (up to fourfold of control at 72 h).
      Likewise, an increase in the specific activity of alkaline phosphatase (fourfold
      at 6 days) and collagen (twofold at 7 days) was observed. Platelet-rich plasma
      also enhanced human gingival fibroblasts proliferation by twofold, whereas it
      inhibited human keratinocytes growth by 40%, with respect to their own controls
      at 72 h. CONCLUSION: Cell populations related to periodontal tissue were
      differently affected by platelet-rich plasma. In fact, a strong stimulation of
      human periodontal ligament cells proliferation, a minor increase in the growth
      rate of human gingival fibroblasts and a marked decrease of human keratinocytes
      proliferation were evident. In addition, in human periodontal ligament cells
      increased collagen and alkaline phosphatase activity levels were observed. These
      findings appear interesting in view of platelet-rich plasma utilization in
      periodontal regeneration.

PMID- 16302929
TI  - Do we realize when we do not know? Recognizing uncertainty in clinical medicine.

PMID- 16302930
TI  - Blunt trauma cardiac tamponade: what really counts in management.

PMID- 16302931
TI  - Does the detection of occult pneumothorax by the focused assessment with
      sonography trauma examination value add to the management of the trauma patient?

PMID- 16302932
TI  - Sourcing toxicology treatment advice.

PMID- 16302933
TI  - Professional issues in emergency medicine: UK perspective.
AB  - The present paper describes the history, the professional development and current
      state of the specialty of emergency medicine in the UK, and outlines the role of
      parent bodies that administer the specialty.

PMID- 16302934
TI  - Impact on patients triage distribution utilizing the Australasian Triage Scale
      compared with its predecessor the National Triage Scale.
AB  - OBJECTIVE: To assess the impact of the change from the National Triage Scale
      (NTS) to the Australasian Triage Scale (ATS) within a hospital ED. METHODS: A
      retrospective audit of consecutive adult patients attending the ED of Auckland
      Hospital from July to September 2001, during which patients were triaged
      according to the NTS, were compared with patients triaged according to the ATS
      during July to September 2002. RESULTS: In total, 8715 patients attended the
      department during July to September 2001 compared with 9047 patients during July
      to September 2002. There was a significant shift in the triage ratios with
      patient number increases of 28 and 24% in triage categories two and three,
      respectively, and decreases of 15 and 67% in categories four and five,
      respectively. CONCLUSIONS: The revision of the ATS has had a significant impact
      on the triage distribution of patients who present to ED. The change of
      distribution might have implications for meeting performance criteria and
      assessing casemix.

PMID- 16302935
TI  - Factors associated with walkout of patients from New South Wales hospital
      emergency departments, Australia.
AB  - OBJECTIVE: To explore the association between daily patient numbers,
      sociodemographic, clinical and system characteristics and walkout rates of
      patients from New South Wales (NSW) public hospital ED (without seeing a medical
      officer). METHODS: This was a secondary analysis of the NSW Emergency Department
      Data Collection, between 1 January 1999 and 31 December 2001, with a total of 4
      356 323 ED attendances. Bivariate and multiple logistic regression analyses were
      performed to explore the relationship of walkout from ED and explanatory
      variables. RESULTS: About 5.7% of the patients attending in NSW public hospital
      ED left without seeing a doctor. The results from bivariate and multivariate
      analyses revealed that walkout rates significantly varied by sociodemographic and
      clinical characteristics of the patients. Patient groups that more likely to walk
      out were those aged 15-44 years, from a non-English-speaking background,
      Aboriginal, with lower socioeconomic status, with no private health insurance
      coverage and longer waiting times for triage. Patient volume in the ED showed a
      significant positive association with walkout rates. CONCLUSIONS: After adjusting
      for triage category (urgency of presentation) and triage time, patients from
      lower socioeconomic backgrounds and those without private health insurance
      coverage were more likely to leave ED without treatment. These results have
      important implications for Health Services. Future strategies aimed at minimizing
      walkouts from public hospital ED should prioritize and target factors identified
      in the present study.

PMID- 16302936
TI  - Prehospital intubation and chest decompression is associated with unexpected
      survival in major thoracic blunt trauma.
AB  - OBJECTIVE: Application of the Trauma and Injury Severity Score (TRISS) to a
      trauma population identifies patients with 'unexpected survival'. This study used
      TRISS analysis to identify 'unexpected survivors' suffering major thoracic
      trauma, who survived to hospital discharge. Further analysis determined
      prehospital interventions that appeared to contribute to 'unexpected survival'.
      METHODS: The present study was a single-centre, retrospective case review with
      comparative statistical analysis. Patients were identified from the Alfred Trauma
      Registry between 1 July 2002 and 30 June 2003. RESULTS: There were 336 adult
      trauma patients treated at The Alfred Trauma Centre with an Injury Severity Score
      >15 (major trauma) and at least one thoracic Anatomical Injury Score of 3
      (severe) or greater. Of the eligible patients, 322/336 (95.8%, 95%[confidence
      interval] CI 95.1-96.5%) had complete data available for analysis. The study
      population mortality was 42/322 (13.0%, 95% CI 12.3-13.7%). There were 20
      'unexpected survivors' (5.9%) and 5 (1.5%) 'unexpected deaths' on TRISS analysis.
      Chest decompression and/or endotracheal intubation prehospital was performed on
      16/20 'unexpected survivors'. GCS for 'unexpected survivors' and 'expected
      deaths' (3.8 vs 3.5, P = 0.27) was not a predictor of survival. Respiratory rate
      per minute (16.2 vs 8.8, P = 0.01) and systolic blood pressure - mmHg (98 vs 80,
      P = 0.03) were significantly greater in the 'unexpected survivors' group compared
      with the 'expected death' group. CONCLUSION: For patients sustaining severe
      thoracic blunt trauma, prehospital intubation and chest decompression appear to
      be associated with unexpected survival. A low GCS at scene is not predictive of
      'unexpected survival' or 'expected death'.

PMID- 16302937
TI  - Self-reported antibiotic compliance: emergency department to general practitioner
      follow up.
AB  - BACKGROUND: General practitioner (GP) follow up is important in the management of
      patients who are discharged from an ED. OBJECTIVES: To determine the antibiotic
      compliance and GP follow-up compliance rates in a population of patients seen and
      discharged from the ED with an antibiotic prescription. To test the hypothesis
      that the ability to nominate a GP is associated with improved antibiotic and GP
      follow-up compliance. DESIGN: A prospective cohort study enrolling consecutive
      adults who were discharged from the ED with antibiotic prescriptions over a 3
      month period. Patients were divided into those who nominated a GP at the time of
      ED presentation and those who did not. Two weeks after enrollment, patients were
      contacted and asked standardized questions regarding compliance. RESULTS: In
      total, 123 patients were enrolled into the study. Of patients 76% were able to
      nominate a GP upon ED presentation. Analysis revealed that those patients who
      were able to nominate a GP had better compliance to follow up instructions (85 vs
      44%, P < 0.01) and improved antibiotic compliance (99 vs 88%, P = 0.01).
      CONCLUSION: The majority of patients who were seen and discharged from the ED
      with an antibiotic prescription were able to nominate a GP and this was
      associated with improved follow-up compliance and antibiotic compliance.
      Improving follow-up compliance and thus the quality of patient care would involve
      identifying those patients who present to the ED who are unable to nominate a GP.

PMID- 16302938
TI  - Non-urgent presentations to a paediatric emergency department: parental
      behaviours, expectations and outcomes.
AB  - OBJECTIVES: To identify factors that influence the attendance of children with
      non-urgent medical problems to a tertiary paediatric ED and to define parental
      expectations of the hospital visit. METHODS: A questionnaire administered to a
      convenience sample of 200 parents/carers who attended the paediatric ED and whose
      children were categorized as having non-urgent problems that had been present for
      at least 4 weeks. Subsequent outpatient attendances were then analysed
      retrospectively. RESULTS: Most patients had visited a general practitioner but
      remained unhappy with the outcome of the consultation. The hospital was expected
      to provide immediate diagnosis and initiate appropriate treatment by the vast
      majority of parent. Only four patients required admission. CONCLUSIONS: The
      expectations of parents who attend the paediatric ED with children who have non
      urgent chronic complaints are high. Rapid access to outpatient clinics might
      provide an acceptable alternative for these patients, and free valuable ED
      resources.

PMID- 16302939
TI  - Techniques for reduction of anteroinferior shoulder dislocation.
AB  - Dislocation of the shoulder joint is common. The shoulder is affected in up to
      60% of all major joint dislocations, one study citing an incidence of 1.7% in the
      general population. The most common form is anteroinferior dislocation. A variety
      of techniques to reduce shoulder dislocation has been described. The key to
      successful relocation is a thorough understanding of the anatomy of both the
      enlocated and the dislocated shoulder joint.

PMID- 16302940
TI  - Primary care patients in the emergency department: who are they? A review of the
      definition of the 'primary care patient' in the emergency department.
AB  - OBJECTIVE: To review the definition of 'primary care' and 'inappropriate'
      patients in ED and develop a generally acceptable working definition of a
      'primary care' presentation in ED. METHOD: A Medline review of articles on
      primary care in ED and the definitions used. RESULTS: A total of 34 reviewed
      papers contained a proposed definition or comment on the definition for potential
      'primary care', 'general practice', or 'inappropriate' patients in ED. A
      representative definition was developed premised on the common factors in these
      papers: low urgency/acuity--triage categories four or five in the Australasian
      Triage Scale, self-referred--by definition, patients referred by general
      practitioner/community primary medical services are not primary care cases
      because a primary care service has referred them on, presenting for a new episode
      of care (i.e. not a planned return because planned returns are not self
      referred), unlikely to be admitted (in the opinion of Emergency Nurse
      interviewers) or ultimately not admitted. DISCUSSION: This definition can be
      applied either prospectively or retrospectively, depending on the purpose.
      Appropriateness must be considered in light of a legitimate role for ED in
      primary care and the balance of resources between primary care and emergency
      medicine in local settings.

PMID- 16302941
TI  - Difference in trauma team activation criteria between hospitals within the same
      region.
AB  - OBJECTIVES: The present study was conducted to establish the current criteria for
      trauma team activation (TTA) in hospitals in the Metropolitan Sydney area, and
      examine the rationale behind their use. METHODS: A cross-sectional survey was
      undertaken of the seven hospitals in the Metropolitan Sydney area designated to
      receive adult major trauma in March 2004. Trauma coordinators in each hospital
      provided the criteria used for adult TTA within their hospital. RESULTS: All
      seven hospitals replied with their TTA criteria and completed the survey. The
      results show a wide variation in those criteria used by hospitals to activate
      their trauma team. Universally used criteria included penetrating injury to the
      head, neck or torso, limb amputation, spinal cord injury and systolic blood
      pressure <90 mmHg. Physiological limits for TTA varied between hospitals, with
      different limits for pulse rate and GCS used in different hospitals. All
      hospitals used mechanism of injury criteria alone as an activation prompt.
      CONCLUSIONS: The criteria for TTA differ between hospitals within the same
      region. The criteria currently used will result in over-triage of trauma
      patients, but this might be of benefit in training the trauma team in centres
      that do not see a large volume of trauma patients. There are several advantages
      in standardization of criteria including optimization of patient care, training,
      research and audit. Further work is needed to validate existing criteria for use
      throughout the region.

PMID- 16302942
TI  - Occult pneumothorax in trauma patients: should this be sought in the focused
      assessment with sonography for trauma examination?
AB  - OBJECTIVE: At present, CT scan is the gold standard for detecting occult
      traumatic pneumothorax not apparent on supine chest X-ray radiograph. Recently
      there were suggestions to expand focused assessment with sonography for trauma
      (FAST) to include thoracic ultrasound for detecting pneumothorax. The aim of the
      present study is to determine the incidence of occult pneumothorax (as shown by
      CT) in the subgroup of trauma patients undergoing FAST. METHODS: Review of all
      trauma patients with FAST done from 1 June 2001 to 31 October 2002. Incidence of
      occult pneumothorax as diagnosed by CT was determined. Patients were not counted
      as having true occult pneumothorax if they had chest drains inserted before
      arrival or imaging studies. Selected clinical findings were tested for
      association with occult pneumothorax. RESULTS: In total, 143 patients underwent
      FAST, of whom 137 (95.8%) had chest X-ray examination performed. Of the 137
      patients 59 required CT abdomen and/or thorax. Occult pneumothorax was found in
      three patients (2.1%). A history of thorax and/or abdominal injury plus one or
      more of: (i) mechanisms potentially causing major trauma; (ii) abnormal chest
      examination; and (iii) chest X-ray radiograph abnormality in the absence of
      pneumothorax, was significantly associated with the presence of occult
      pneumothorax (P = 0.03, Fisher's exact test; sensitivity: 100%; specificity: 71%;
      likelihood ratio: 3.42). CONCLUSION: The incidence of occult pneumothorax in the
      subgroup of trauma patients undergoing FAST is low. It implies that routine
      screening for its presence by adding thoracic ultrasound to FAST is unnecessary.
      Identifying those at risk of occult pneumothorax for further investigation
      appeared feasible.

PMID- 16302943
TI  - Definitive management of acute cardiac tamponade secondary to blunt trauma.
AB  - Blunt cardiac injuries are a leading cause of fatalities following motor-vehicle
      accidents. Injury to the heart is involved in 20% of road traffic deaths.
      Structural cardiac injuries (i.e. chamber rupture or perforation) carry a high
      mortality rate and patients rarely survive long enough to reach hospital. Chamber
      rupture is present at autopsy in 36-65% of death from blunt cardiac trauma,
      whereas in clinical series it is present in 0.3-0.9% of cases and is an uncommon
      clinical finding. Patients with large ruptures or perforations usually die at the
      scene or in transit--the rupture of a cardiac cavity, coronary artery or
      intrapericardial portion of a major vein or artery is usually instantly fatal
      because of acute tamponade. The small, rare, remaining group of patients who
      survive to hospital presentation usually have tears in a cavity under low
      pressure and prompt diagnosis and surgery can now lead to a survival rate of 70
      80% in experienced trauma centres. As regional trauma systems evolve, patients
      with severe, but potentially survivable cardiac injury are surviving to ED. Two
      distinct syndromes are apparent--haemorrhagic shock and cardiac tamponade. Any
      patient with severe chest trauma, hypotension disproportionate to estimated loss
      of blood or with an inadequate response to fluid administration should be
      suspected of having a cardiac cause of shock. For patients with severe
      hypotension or in extremis, the treatment of choice is resuscitative thoracotomy
      with pericardotomy. Closed chest cardiopulmonary resuscitation is ineffective in
      these circumstances. Blunt traumatic cardiac injury presenting with shock is
      associated with a poor prognosis. The majority of survivors of blunt or
      penetrating cardiac injury present to the ED/trauma centre with vital signs. The
      main pathophysiologic determinant for most survivors is acute pericardial
      tamponade. The presence of normal clinical signs or normal ECG studies does not
      exclude tamponade. In recent years the widespread availability and use of
      ultrasound for the initial assessment of severely injured patients has
      facilitated the early diagnosis of cardiac tamponade and associated cardiac
      injuries. Two cases of survival from blunt traumatic cardiac trauma are described
      in the present paper to demonstrate survivability in the context of rapid
      assessment and intervention.

PMID- 16302944
TI  - Use of glycoprotein IIb/IIIa inhibitors in unstable angina and non-ST-elevation
      myocardial infarction.
AB  - Acute coronary syndromes (ACS) are a major cause of morbidity and mortality in
      Western society. The commonest underlying pathology is the coronary
      atherosclerotic plaque complicated by thrombosis. Platelets play a central role.
      As the glycoprotein IIb/IIIa receptor is involved in the final step of platelet
      thrombus formation development and investigation of its blockage in ACS is at the
      fore. Initial hospital management of ACS occur in the ED setting. The present
      article outlines the above topics and clarifies the place of glycoprotein
      IIb/IIIa receptor inhibition in ED.

PMID- 16302945
TI  - Quality of poisoning management advice in the Monthly Index of Medical
      Specialties Annual.
AB  - BACKGROUND: The Monthly Index of Medical Specialties (MIMS) contains Therapeutic
      Goods Administration-approved product information supplied by manufacturers. It
      is widely used by health-care professionals but is not specifically designed as a
      toxicology reference. OBJECTIVES: To determine how widespread the use of MIMS is
      as a toxicology reference. To evaluate the quality of poisoning management advice
      it contains. METHODS: First, a survey of 500 consecutive calls to the NSW Poison
      Information Centre (PIC) was undertaken asking health-care workers which
      toxicology references were consulted prior to calling and which references they
      would use if the PIC were not available. Second, a consensus opinion for
      poisoning management was obtained, for 25 medications which are either commonly
      involved in poisoning or potentially life-threatening in overdose, by review of 5
      current toxicology references for contraindicated treatments, ineffective
      treatments and specific recommended treatments and antidotes. MIMS poisoning
      management advice was then compared with this toxicology consensus opinion.
      RESULTS: In total, 276 doctors and 222 nurses were surveyed. Prior to calling the
      PIC 22.8% of doctors and 6.8% of nurses consulted MIMS. In total, 25.7% of
      doctors and 39.6% nurses stated they would use the MIMS for poisoning management
      advice if the PIC were not available. For the 25 drugs assessed, 14 contained
      inaccurate poisoning management: 1 recommended ineffective treatments and 14
      omitted specific treatments or antidotes. CONCLUSION: The MIMS is often used as a
      toxicology reference by physicians prior to calling the PIC. It contains a number
      of significant inaccuracies pertaining to management of poisonings and should not
      be used as a primary reference for poisoning advice.

PMID- 16302946
TI  - Unusual cause of sudden onset headache: spontaneous intracranial hypotension.
AB  - Spontaneous intracranial hypotension is a very distinctive but unusual cause of
      acute headache. The postural nature of the headache can be easily overlooked in
      the celerity to exclude subarachnoid haemorrhage. We describe the clinical and
      radiological features of a case that emphasizes some of the diagnostic
      difficulties. An approach to management and treatment for this condition is
      outlined.

PMID- 16302949
TI  - Hear ye, hear ye: emergency department 10 commandments.

PMID- 16302950
TI  - Prioritizing health-care delivery in the Solomon Islands: first things first.

PMID- 16302951
TI  - Loop-mediated isothermal amplification: an emerging technology for detection of
      fish and shellfish pathogens.
AB  - Fish and shellfish diseases are a constant threat to the sustainability and
      economic viability of aquaculture. Early diagnosis plays a vital role in
      management of fish and shellfish diseases. Traditionally, various biochemical and
      serological tests have been used for fish disease diagnosis. However, the time
      and expertise required for such diagnoses makes it difficult for aquaculturists
      to easily adopt them under production conditions. Polymerase chain reaction and
      probe-based nucleic acid detection have become increasingly popular in fish and
      shellfish diagnostics. Recently, a novel technique called loop-mediated
      isothermal amplification (LAMP) has been developed, which is highly sensitive and
      rapid. LAMP has been used for the detection of bacterial, viral, fungal and
      parasitic diseases in both animal and plants. In aquaculture, LAMP-based
      detection of pathogens like Edwardsiella tarda, E. ictaluri, Nocardia seriolae,
      Tetracapsuloides bryosalmonae, white spot syndrome virus and infectious
      haematopoietic necrosis virus have been reported. In this review, the application
      of LAMP for the detection of aquaculture-associated pathogens is discussed.

PMID- 16302952
TI  - The effect of environmental factors on the distribution of Neoparamoeba
      pemaquidensis in Tasmania.
AB  - Aquaculture in Tasmania is mostly carried out in estuaries. These estuarine
      habitats show a great variety and form unique environments in which Neoparamoeba
      pemaquidensis, the amoebic gill disease (AGD)-causing protozoan, may or may not
      survive. Tasmania is divided into two zones, one where AGD is present and one
      where AGD is absent, but any ecological data to rationalize this distribution is
      lacking. In in vitro trials N. pemaquidensis strains were exposed to different
      concentrations of ammonium sulphate, copper sulphate, copper sulphate and tannin,
      and different Neoparamoeba densities, salinities and temperatures. A trial using
      field water samples investigated the survival of N. pemaquidensis in waters
      sourced from AGD-free and AGD-positive zones, and water analysis was performed to
      determine any differences. Significantly decreased protozoan survival was found
      with exposure to increasing copper sulphate concentrations from 10 to 100,000
      microM (P < 0.001), salinity of 15 per thousand (P < 0.001), low Neoparamoeba
      densities of 625 and 1,250 cells mL(-1) (P = 0.0005), and water sourced from
      Macquarie Harbour (P < 0.001). The water chemistry of this AGD-free zone showed
      significantly lower dissolved calcium and magnesium concentrations which may
      contribute to this area being AGD-free. Understanding of the ecology of N.
      pemaquidensis will enable better control and prevention strategies for Tasmanian
      salmon growers.

PMID- 16302953
TI  - Modulation of beta-actin, insulin-like growth factor 1 and glucose-6-phosphate
      dehydrogenase gene expression during vibriosis of sea bream, Sparus
      (=Rhabdosargus) sarba Forsskal.
AB  - Gene expression changes, related to growth regulation, were investigated in
      silver sea bream, Sparus (=Rhabdosargus) sarba, subjected to vibriosis. Using
      reverse transcriptase polymerase chain reaction assays, transcript levels of beta
      actin, insulin-like growth factor 1 (IGF-1) and glucose-6-phosphate dehydrogenase
      (G6PDH) were analysed. A tissue-specific response for beta-actin was found, as
      transcript levels in the kidney increased during early- and mid-stage vibriosis,
      but remained unchanged in liver tissue. The gene transcript levels of IGF-1 were
      found to decrease in both liver and kidney from an early stage of vibriosis. The
      gene transcript levels of G6PDH increased at early and mid stages of vibriosis in
      liver and kidney before decreasing during the late stage of vibriosis. Further
      studies on G6PDH demonstrated that chemical inhibition of G6PDH in silver sea
      bream fibroblasts resulted in increased cell death upon exposure to hydrogen
      peroxide. The results from the present study demonstrate the complexity of growth
      related gene expression events that occur in fish tissues during disease.

PMID- 16302954
TI  - A mathematical model of the growth of sea lice, Lepeophtheirus salmonis,
      populations on farmed Atlantic salmon, Salmo salar L., in Scotland and its use in
      the assessment of treatment strategies.
AB  - Sea lice are a persistent problem for farmed and wild salmonid populations.
      Control can be achieved through the use of veterinary medicines. A model was
      developed to describe the patterns of sea lice infection on salmon farms in
      Scotland and to predict the likely effect of various treatment strategies. This
      model takes into account development rates and mortality using compartments
      representing life history stages and external infection pressure. The national
      sea lice infection pattern was described using parameters representing stage
      survival, background infection levels and egg viability rates. The patterns
      observed across farms varied greatly and the model gave broad agreement to
      observed trends with different parameters being required in the model for sites
      using hydrogen peroxide and cypermethrin treatments. The parameter estimates
      suggest that the background infection pressure on sites where cypermethrin was
      administered was higher than for those using hydrogen peroxide. Both models had
      comparable magnitudes of sensitivity with survival from one stage to another
      being the most sensitive parameter, followed by feedback rates at which gravid
      females produce eggs, with background infection levels the least sensitive. The
      effect of different cypermethrin treatment strategies was assessed using the
      model. Increasing treatments in a production cycle gave more effective control.
      However, the model showed that timing of treatments is most important if sea lice
      are to be effectively controlled.

PMID- 16302955
TI  - Detection of Renibacterium salmoninarum in chinook salmon, Oncorhynchus
      tshawytscha (Walbaum), using quantitative PCR.
AB  - A quantitative polymerase chain reaction (QPCR) assay has been developed to
      detect varying levels of Renibacterium salmoninarum, the causative agent of
      bacterial kidney disease. This assay allows for the direct enumeration of
      bacterial DNA or RNA copy number within tissues and body fluids. The assay can be
      applied non-lethally and can be used to determine whether R. salmoninarum is
      transcriptionally active. The presence of R. salmoninarum in kidney tissues from
      430 chinook salmon collected from five Idaho Fish and Game operated hatcheries
      was initially evaluated using the widely employed enzyme-linked immunosorbent
      assay (ELISA) with two sets of Kirkegaard and Perry Laboratories polyclonal
      antibodies, 'mother batches' 1 and 2. The same tissue samples were then analysed
      using the novel QPCR assay and the results compared. At moderate to high levels
      of infection [optical density (OD > 0.5)], ELISA values and estimated DNA copy
      number were highly correlated (r(2) > 0.80), although correlation to specific
      antibody batches varied. However, lower ELISA values (OD < 0.5) observed with
      either antibody batch did not correlate well with the QPCR assay (R(2) <or=
      0.43). Negative controls, run concurrently with the PCR assay, did not indicate
      extraneous DNA contamination in the PCR samples.

PMID- 16302956
TI  - Successful treatment of largemouth bass, Micropterus salmoides (L.), with
      epitheliocystis hyperinfection.

PMID- 16302958
TI  - Amyloid fibrils.

PMID- 16302959
TI  - Aspects on human amyloid forms and their fibril polypeptides.
AB  - Amyloid is an in vivo fibrillar substance containing a fibril protein and several
      additional molecules. Presently, 25 proteins have been reported as main fibril
      components. Why just a few proteins form amyloid in vivo is still insufficiently
      understood. Many fibril proteins appear as fragments of larger precursors and for
      some types it is not clear whether fragmentation comes before or after
      fibrillation. The self-assembly by amyloid proteins can be speeded up by seeding
      with preformed fibrils. In mice, systemic amyloidoses are transmissible by a
      seeding mechanism. Whether this prion-like mechanism occurs in humans is not
      known, but can definitely not be ruled out.

PMID- 16302960
TI  - Structures for amyloid fibrils.
AB  - Alzheimer's disease and Creutzfeldt-Jakob disease are the best-known examples of
      a group of diseases known as the amyloidoses. They are characterized by the
      extracellular deposition of toxic, insoluble amyloid fibrils. Knowledge of the
      structure of these fibrils is essential for understanding the process of
      pathology of the amyloidoses and for the rational design of drugs to inhibit or
      reverse amyloid formation. Structural models have been built using information
      from a wide variety of techniques, including X-ray diffraction, electron
      microscopy, solid state NMR and EPR. Recent advances have been made in
      understanding the architecture of the amyloid fibril. Here, we describe and
      compare postulated structural models for the mature amyloid fibril and discuss
      how the ordered structure of amyloid contributes to its stability.

PMID- 16302961
TI  - The Yin and Yang of protein folding.
AB  - The study of protein aggregation saw a renaissance in the last decade, when it
      was discovered that aggregation is the cause of several human diseases, making
      this field of research one of the most exciting frontiers in science today.
      Building on knowledge about protein folding energy landscapes, determined using
      an array of biophysical methods, theory and simulation, new light is now being
      shed on some of the key questions in protein-misfolding diseases. This review
      will focus on the mechanisms of protein folding and amyloid fibril formation,
      concentrating on the role of partially folded states in these processes, the
      complexity of the free energy landscape, and the potentials for the development
      of future therapeutic strategies based on a full biophysical description of the
      combined folding and aggregation free-energy surface.

PMID- 16302962
TI  - Mechanisms of amyloid fibril self-assembly and inhibition. Model short peptides
      as a key research tool.
AB  - The formation of amyloid fibrils is associated with various human medical
      disorders of unrelated origin. Recent research indicates that self-assembled
      amyloid fibrils are also involved in physiological processes in several micro
      organisms. Yet, the molecular basis for the recognition and self-assembly
      processes mediating the formation of such structures from their soluble protein
      precursors is not fully understood. Short peptide models have provided novel
      insight into the mechanistic issues of amyloid formation, revealing that very
      short peptides (as short as a tetrapeptide) contain all the necessary molecular
      information for forming typical amyloid fibrils. A careful analysis of short
      peptides has not only facilitated the identification of molecular recognition
      modules that promote the interaction and self-assembly of fibrils but also
      revealed that aromatic interactions are important in many cases of amyloid
      formation. The realization of the role of aromatic moieties in fibril formation
      is currently being used to develop novel inhibitors that can serve as therapeutic
      agents to treat amyloid-associated disorders.

PMID- 16302963
TI  - The influence of heterodimer partner ultraspiracle/retinoid X receptor on the
      function of ecdysone receptor.
AB  - A pair of nuclear receptors, ecdysone receptor (EcR) and ultraspiracle (USP),
      heterodimerize and transduce ecdysteroid signals. The EcR and its nonsteroidal
      ligands are being developed for regulation of transgene expression in humans,
      animals and plants. In mammalian cells, EcR:USP heterodimers can function in the
      absence of ligand, but EcR/retinoid X receptor (EcR:RXR) heterodimers require the
      presence of ligand for activation. The heterodimer partner of EcR can influence
      ligand sensitivity of EcR so that the EcR/Locusta migratoria RXR (EcR:LmRXR)
      heterodimers are activated at lower concentrations of ligand when compared with
      the concentrations of ligand required for the activation of EcR/Homo sapiens RXR
      (EcR:HsRXR) heterodimers. Analysis of chimeric RXRs containing regions of LmRXR
      and HsRXR and point mutants of HsRXR showed that the amino acid residues present
      in helix 9 and in the two loops on either end of helix 9 are responsible for
      improved activity of LmRXR. The EcR:Lm-HsRXR chimera heterodimer induced reporter
      genes with nanomolar concentration of ligand compared with the micromolar
      concentration of ligand required for activating the EcR:HsRXR heterodimer. The
      EcR:Lm-HsRXR chimera heterodimer, but not the EcR:HsRXR heterodimer, supported
      ligand-dependent induction of reporter gene in a C57BL/6 mouse model.

PMID- 16302964
TI  - Template-independent ligation of single-stranded DNA by T4 DNA ligase.
AB  - T4 DNA ligase is one of the workhorses of molecular biology and used in various
      biotechnological applications. Here we report that this ligase, unlike
      Escherichia coli DNA ligase, Taq DNA ligase and Ampligase, is able to join the
      ends of single-stranded DNA in the absence of any duplex DNA structure at the
      ligation site. Such nontemplated ligation of DNA oligomers catalyzed by T4 DNA
      ligase occurs with a very low yield, as assessed by quantitative competitive PCR,
      between 10(-6) and 10(-4) at oligonucleotide concentrations in the range 0.1-10
      nm, and thus is insignificant in many molecular biological applications of T4 DNA
      ligase. However, this side reaction may be of paramount importance for diagnostic
      detection methods that rely on template-dependent or target-dependent DNA probe
      ligation in combination with amplification techniques, such as PCR or rolling
      circle amplification, because it can lead to nonspecific background signals or
      false positives. Comparison of ligation yields obtained with substrates differing
      in their strandedness at the terminal segments involved in ligation shows that an
      acceptor duplex DNA segment bearing a 3'-hydroxy end, but lacking a 5'-phosphate
      end, is sufficient to play a role as a cofactor in blunt-end ligation.

PMID- 16302965
TI  - Purification and sequence identification of anserinase.
AB  - Anserinase (Xaa-methyl-His dipeptidase, EC 3.4.13.5) is a dipeptidase that mainly
      catalyzes the hydrolysis of Nalpha-acetylhistidine in the brain, retina and
      vitreous body of all poikilothermic vertebrates. The gene encoding anserinase has
      not been previously identified. We report the molecular identification of
      anserinase, purified from brain of Nile tilapia Oreochromis niloticus. The
      determination of the N-terminal sequence of the purified anserinase allowed the
      design of primers permitting the corresponding cDNA to be cloned by PCR. The
      anserinase cDNA has an ORF of 1485 nucleotides and encodes a signal peptide of 18
      amino acids and a mature protein of 476 amino acids with a predicted molecular
      mass of 53.3 kDa. Sequence analysis showed that anserinase is a member of the
      M20A metallopeptidase subfamily in MEROPS peptidase database, to which 'serum'
      carnosinase (EC 3.4.13.20) and cytosolic nonspecific dipeptidase (EC 3.4.13.18,
      CNDP) belong. A cDNA encoding CNDP-like protein was also isolated from tilapia
      brain. Whereas anserinase mRNA was detected only in brain, retina, kidney and
      skeletal muscle, CNDP-like protein mRNA was detected in all tissues examined.

PMID- 16302966
TI  - Fish and molluscan metallothioneins.
AB  - Metallothioneins (MTs) are noncatalytic peptides involved in storage of essential
      ions, detoxification of nonessential metals, and scavenging of oxyradicals. They
      exhibit an unusual primary sequence and unique 3D arrangement. Whereas vertebrate
      MTs are characterized by the well-known dumbbell shape, with a beta domain that
      binds three bivalent metal ions and an alpha domain that binds four ions,
      molluscan MT structure is still poorly understood. For this reason we compared
      two MTs from aquatic organisms that differ markedly in primary structure: MT 10
      from the invertebrate Mytilus galloprovincialis and MT A from Oncorhyncus mykiss.
      Both proteins were overexpressed in Escherichia coli as glutathione S-transferase
      fusion proteins, and the MT moiety was recovered after protease cleavage. The MTs
      were analyzed by gel electrophoresis and tested for their differential reactivity
      with alkylating and reducing agents. Although they show an identical cadmium
      content and a similar metal-binding ability, spectropolarimetric analysis
      disclosed significant differences in the Cd7-MT secondary conformation. These
      structural differences reflect the thermal stability and metal transport of the
      two proteins. When metal transfer from Cd7-MT to 4-(2-pyridylazo)resorcinol was
      measured, the mussel MT was more reactive than the fish protein. This confirms
      that the differences in the primary sequence of MT 10 give rise to peculiar
      secondary conformation, which in turn reflects its reactivity and stability. The
      functional differences between the two MTs are due to specific structural
      properties and may be related to the different lifestyles of the two organisms.

PMID- 16302967
TI  - Evaluation of detergents for the soluble expression of alpha-helical and beta
      barrel-type integral membrane proteins by a preparative scale individual cell
      free expression system.
AB  - Cell-free expression has become a highly promising tool for the fast and
      efficient production of integral membrane proteins. The proteins can be produced
      as precipitates that solubilize in mild detergents usually without any prior
      denaturation steps. Alternatively, membrane proteins can be synthesized in a
      soluble form by adding detergents to the cell-free system. However, the effects
      of a representative variety of detergents on the production, solubility and
      activity of a wider range of membrane proteins upon cell-free expression are
      currently unknown. We therefore analyzed the cell-free expression of three
      structurally very different membrane proteins, namely the bacterial alpha-helical
      multidrug transporter, EmrE, the beta-barrel nucleoside transporter, Tsx, and the
      porcine vasopressin receptor of the eukaryotic superfamily of G-protein coupled
      receptors. All three membrane proteins could be produced in amounts of several mg
      per one ml of reaction mixture. In general, the detergent 1-myristoyl-2-hydroxy
      sn-glycero-3-[phospho-rac-(1-glycerol)] was found to be most effective for the
      resolubilization of membrane protein precipitates, while long chain
      polyoxyethylene-alkyl-ethers proved to be most suitable for the soluble
      expression of all three types of membrane proteins. The yield of soluble
      expressed membrane protein remained relatively stable above a certain threshold
      concentration of the detergents. We report, for the first time, the high-level
      cell-free expression of a beta-barrel type membrane protein in a functional form.
      Structural and functional variations of the analyzed membrane proteins are
      evident that correspond with the mode of expression and that depend on the
      supplied detergent.

PMID- 16302968
TI  - The variable C-terminal extension of G-protein-coupled receptor kinase 6
      constitutes an accessorial autoregulatory domain.
AB  - G-protein-coupled receptor kinases (GRK) are known to phosphorylate agonist
      occupied G-protein-coupled receptors. We expressed and functionally characterized
      mouse GRK6 proteins encoded by four distinct mRNAs generated by alternative RNA
      splicing from a single gene, mGRK6-A to mGRK6-D. Three isoforms, mGRK6-A to mGRK6
      C differ in their C-terminal-most portion, which is known to mediate membrane
      and/or receptor interaction and regulate the activity of GRK4-like kinases. One
      isoform, mGRK6-D, is identical to the other mGRK6 variants in the N-terminal
      region, but carries an incomplete catalytical domain. Mouse GRK6-D was
      catalytically inactive and specifically present in the nucleus of transfected
      cells. Recombinant mouse GRK6-A to mGRK6-C were found to be membrane-associated
      in cell-free systems and in transfected COS-7 cells, suggesting that the very C
      terminus of GRK6-A, lacking in GRK6-B and mGRK6-C and carrying consensus sites
      for palmitoylation, is not required for membrane interaction. Interestingly, the
      shortest catalytically active variant, mGRK6-C, was conspicuously more active in
      phosphorylating light-activated rhodopsin than mGRK6-A and mGRK6-B, implying that
      the C-terminus of the latter two variants may fulfil an autoinhibitory function.
      Mutation and removal of C-terminal-most region of mGRK6-A by site-directed
      mutagenesis revealed that this region contains three autoregulatory elements: two
      discontinuous inhibitory elements consisting of a single residue, D560, and the
      sequence between residues S566 and L576, and an intervening stimulatory element.
      The results suggest that mGRK6-C may be considered a basic, prototypic
      representative of the GRK4-like kinases, which is capable of interacting with
      both plasma membrane and its receptor substrate, but is resistant to further
      regulatory modification conferred to the prototype via C-terminal extension.

PMID- 16302969
TI  - SHIP2 interaction with the cytoskeletal protein Vinexin.
AB  - The src homology 2 (SH2) domain-containing inositol 5-phosphatase 2 (SHIP2)
      catalyses the dephosphorylation of phosphatidylinositol 3,4,5-trisphosphate
      [PtdIns(3,4,5)P3] to phosphatidylinositol 3,4-bisphosphate [PtdIns(3,4)P2]. We
      report the identification of the cytoskeletal protein Vinexin as a protein
      interacting with SHIP2. This was achieved by yeast two-hybrid screening using the
      C-terminal region of SHIP2 as bait. Vinexin has previously been identified as a
      vinculin-binding protein that plays a key role in cell spreading and cytoskeletal
      organization. The interaction between SHIP2 and Vinexin was confirmed in lysates
      of both COS-7 cells and mouse embryonic fibroblasts (MEF). The C-terminus was
      involved in the interaction, as shown by the transfection of a truncated C
      terminus mutant of SHIP2. In addition, we showed the colocalization between
      Vinexin alpha and SHIP2 at the periphery of transfected COS-7 cells. When added
      in vitro to SHIP2, Vinexin did not affect the PtdIns(3,4,5)P3 5-phosphatase
      activity of SHIP2. Enhanced cell adhesion to collagen-I-coated dishes was shown
      upon transfection of either SHIP2 or Vinexin to COS-7 cells. This effect was no
      longer observed with either a catalytic mutant or the C-terminus mutant of SHIP2.
      It also appears SHIP2 specific; this was not seen with SHIP1. Adhesion to the
      same matrix was decreased in SHIP2-/- MEF cells compared with MEF+/+ cells. Our
      data suggest that SHIP2 interaction with Vinexin promotes the localization of
      SHIP2 at the periphery of the cells leaving its catalytic site intact. The
      complex formation between Vinexin and SHIP2 may increase cellular adhesion. The
      data reinforce the concept that SHIP2 is active both as a PtdIns(3,4,5)P3 5
      phosphatase and as a modulator of focal contact formation.

PMID- 16302970
TI  - Structure and mechanism of the ThDP-dependent benzaldehyde lyase from Pseudomonas
      fluorescens.
AB  - Pseudomonas fluorescens is able to grow on R-benzoin as the sole carbon and
      energy source because it harbours the enzyme benzaldehyde lyase that cleaves the
      acyloin linkage using thiamine diphosphate (ThDP) as a cofactor. In the reverse
      reaction, this lyase catalyses the carboligation of two aldehydes with high
      substrate and stereospecificity. The enzyme structure was determined by X-ray
      diffraction at 2.6 A resolution. A structure-based comparison with other proteins
      showed that benzaldehyde lyase belongs to a group of closely related ThDP
      dependent enzymes. The ThDP cofactors of these enzymes are fixed at their two
      ends in separate domains, suspending a comparatively mobile thiazolium ring
      between them. While the residues binding the two ends of ThDP are well conserved,
      the lining of the active centre pocket around the thiazolium moiety varies
      greatly within the group. Accounting for the known reaction chemistry, the
      natural substrate R-benzoin was modelled unambiguously into the active centre of
      the reported benzaldehyde lyase. Due to its substrate spectrum and
      stereospecificity, the enzyme extends the synthetic potential for carboligations
      appreciably.

PMID- 16302971
TI  - The hyperfluidization of mammalian cell membranes acts as a signal to initiate
      the heat shock protein response.
AB  - The concentrations of two structurally distinct membrane fluidizers, the local
      anesthetic benzyl alcohol (BA) and heptanol (HE), were used at concentrations so
      that their addition to K562 cells caused identical increases in the level of
      plasma membrane fluidity as tested by 1,6-diphenyl-1,3,5-hexatriene (DPH)
      anisotropy. The level of membrane fluidization induced by the chemical agents on
      isolated membranes at such concentrations corresponded to the membrane fluidity
      increase seen during a thermal shift up to 42 degrees C. The formation of
      isofluid membrane states in response to the administration of BA or HE resulted
      in almost identical downshifts in the temperature thresholds of the heat shock
      response, accompanied by increases in the expression of genes for stress proteins
      such as heat shock protein (HSP)-70 at the physiological temperature. Similarly
      to thermal stress, the exposure of the cells to these membrane fluidizers
      elicited nearly identical increases of cytosolic Ca2+ concentration in both Ca2+
      containing and Ca2+-free media and also closely similar extents of increase in
      mitochondrial hyperpolarization. We obtained no evidence that the activation of
      heat shock protein expression by membrane fluidizers is induced by a protein
      unfolding signal. We suggest, that the increase of fluidity in specific membrane
      domains, together with subsequent alterations in key cellular events are
      converted into signal(s) leading to activation of heat shock genes.

PMID- 16302972
TI  - Cardiac troponin C-L29Q, related to hypertrophic cardiomyopathy, hinders the
      transduction of the protein kinase A dependent phosphorylation signal from
      cardiac troponin I to C.
AB  - We investigated structural and functional aspects of the first mutation in TNNC1,
      coding for the calcium-binding subunit (cTnC) of cardiac troponin, which was
      detected in a patient with hypertrophic cardiomyopathy [ Hoffmann B, Schmidt
      Traub H, Perrot A, Osterziel KJ & Gessner R (2001) Hum Mut17, 524]. This mutation
      leads to a leucine-glutamine exchange at position 29 in the nonfunctional calcium
      binding site of cTnC. Interestingly, the mutation is located in a putative
      interaction site for the nonphosphorylated N-terminal arm of cardiac troponin I
      (cTnI) [ Finley NL, Abbott MB, Abusamhadneh E, Gaponenko V, Dong W, Seabrook G,
      Howarth JW, Rana M, Solaro RJ, Cheung HC et al. (1999) EJB Lett453, 107-112].
      According to peptide array experiments, the nonphosphorylated cTnI arm interacts
      with cTnC around L29. This interaction is almost abolished by L29Q, as observed
      upon protein kinase A-dependent phosphorylation of cTnI at serine 22 and serine
      23 in wild-type troponin. With CD spectroscopy, minor changes are observed in the
      backbone of Ca2+-free and Ca2+-saturated cTnC upon the L29Q replacement. A small,
      but significant, reduction in calcium sensitivity was detected upon measuring the
      Ca2+-dependent actomyosin subfragment 1 (actoS1)-ATPase activity and the sliding
      velocity of thin filaments. The maximum actoS1-ATPase activity, but not the
      maximum sliding velocity, was significantly enhanced. In addition, we performed
      our investigations at different levels of protein kinase A-dependent
      phosphorylation of cTnI. The in vitro assays mainly showed that the Ca2+
      sensitivity of the actoS1-ATPase activity, and the mean sliding velocity of thin
      filaments, were no longer affected by protein kinase A-dependent phosphorylation
      of cTnI owing to the L29Q exchange in cTnC. The findings imply a hindered
      transduction of the phosphorylation signal from cTnI to cTnC.

PMID- 16302973
TI  - Purification, cDNA cloning, and expression profiles of the cyclobutane pyrimidine
      dimer photolyase of Xenopus laevis.
AB  - Photolyase is a light-dependent enzyme that repairs pyrimidine dimers in DNA. Two
      types of photolyases have been found in frog Xenopus laevis, one for repairing
      cyclobutane pyrimidine dimers (CPD photolyase) and the other for pyrimidine
      pyrimidone (6-4)photoproduct [(6-4)photolyase]. However, little is known about
      the former type of the Xenopus photolyases. To characterize this enzyme and its
      expression profiles, we isolated the entire coding region of a putative CPD
      photolyase cDNA by extending an EST (expressed sequence tag) sequence obtained
      from the Xenopus database. Nucleotide sequence analysis of the cDNA revealed a
      protein of 557 amino acids with close similarity to CPD photolyase of rat
      kangaroo. The identity of this cDNA was further established by the molecular mass
      (65 kDa) and the partial amino acid sequences of the major CPD photolyase that we
      purified from Xenopus ovaries. The gene of this enzyme is expressed in various
      tissues of Xenopus. Even internal organs like heart express relatively high
      levels of mRNA. A much smaller amount was found in skin, although UV damage is
      thought to occur most frequently in this tissue. Such expression profiles suggest
      that CPD photolyase may have roles in addition to the photorepair function.

PMID- 16302974
TI  - Mutual effects of proton and sodium chloride on oxygenation of liganded human
      hemoglobin.
AB  - The different effects of pH and NaCl on individual O2-binding properties of alpha
      and beta subunits within liganded tetramer and dimer of human hemoglobin (HbA)
      were examined in a number of laser time-resolved spectroscopic measurements. A
      previously proposed approach [Dzhagarov BM & Lepeshkevich SV (2004) Chem Phys
      Lett390, 59-64] was used to determine the extent of subunit dissociation rate
      constant difference and subunit affinity difference from a single flash
      photolysis experiment. To investigate the effect of NaCl concentration on the
      association and dissociation rate constants we carried out a series of
      experiments at four different concentrations (0.1, 0.5, 1.0 and 2.0 m NaCl) over
      the pH range of the alkaline Bohr effect. As the data suggest, the individual
      properties of the alpha and beta subunits within the completely liganded
      tetrameric hemoglobin did not depend on pH under salt-free conditions. However,
      different effects NaCl on the individual kinetic properties of the alpha and beta
      subunits were revealed. Regulation of the O2-binding properties of the alpha and
      beta subunits within the liganded tetramer is proposed to be attained in two
      quite different ways.

PMID- 16302975
TI  - Secondary structure assignment of mouse SOCS3 by NMR defines the domain
      boundaries and identifies an unstructured insertion in the SH2 domain.
AB  - SOCS3 is a negative regulator of cytokine signalling that inhibits Janus kinase
      signal transduction and activator of transcription (JAK-STAT) mediated signal
      tranduction by binding to phosphorylated tyrosine residues on intracellular
      subunits of various cytokine receptors, as well as possibly the JAK proteins.
      SOCS3 consists of a short N-terminal sequence followed by a kinase inhibitory
      region, an extended SH2 domain and a C-terminal suppressor of cytokine signalling
      (SOCS) box. SOCS3 and the related protein, cytokine-inducible SH2-containing
      protein, are unique among the SOCS family of proteins in containing a region of
      mostly low complexity sequence, between the SH2 domain and the C-terminal SOCS
      box. Using NMR, we assigned and determined the secondary structure of a murine
      SOCS3 construct. The SH2 domain, unusually, consists of 140 residues, including
      an unstructured insertion of 35 residues. This insertion fits the criteria for a
      PEST sequence and is not required for phosphotyrosine binding, as shown by
      isothermal titration calorimetry. Instead, we propose that the PEST sequence has
      a functional role unrelated to phosphotyrosine binding, possibly mediating
      efficient proteolytic degradation of the protein. The latter half of the kinase
      inhibitory region and the entire extended SH2 subdomain form a single alpha
      helix. The mapping of the true SH2 domain, and the location of its C terminus
      more than 50 residues further downstream than predicted by sequence homology,
      explains a number of previously unexpected results that have shown the importance
      of residues close to the SOCS box for phosphotyrosine binding.

PMID- 16302976
TI  - Intrabodies against the EVH1 domain of Wiskott-Aldrich syndrome protein inhibit T
      cell receptor signaling in transgenic mice T cells.
AB  - Intracellularly expressed antibodies (intrabodies) have been used to inhibit the
      function of various kinds of protein inside cells. However, problems with
      stability and functional expression of intrabodies in the cytosol remain
      unsolved. In this study, we show that single-chain variable fragment (scFv)
      intrabodies constructed with a heavy chain variable (V(H)) leader signal sequence
      at the N-terminus were translocated from the endoplasmic reticulum into the
      cytosol of T lymphocytes and inhibited the function of the target molecule,
      Wiskott-Aldrich syndrome protein (WASP). WASP resides in the cytosol as a
      multifunctional adaptor molecule and mediates actin polymerization and
      interleukin (IL)-2 synthesis in the T-cell receptor (TCR) signaling pathway. It
      has been suggested that an EVH1 domain in the N-terminal region of WASP may
      participate in IL-2 synthesis. In transgenic mice expressing anti-EVH1 scFvs
      derived from hybridoma cells producing WASP-EVH1 mAbs, a large number of scFvs in
      the cytosol and binding between anti-EVH1 scFvs and native WASP in T cells were
      detected by immunoprecipitation analysis. Furthermore, impairment of the
      proliferative response and IL-2 production induced by TCR stimulation which did
      not affect TCR capping was demonstrated in the scFv transgenic T cells. We
      previously described the same T-cell defects in WASP transgenic mice
      overexpressing the EVH1 domain. These results indicate that the EVH1 intrabodies
      inhibit only the EVH1 domain function that regulates IL-2 synthesis signaling
      without affecting the overall domain structure of WASP. The novel procedure
      presented here is a valuable tool for in vivo functional analysis of cytosolic
      proteins.

PMID- 16302977
TI  - Complexes of Thermoactinomyces vulgaris R-47 alpha-amylase 1 and pullulan model
      oligossacharides provide new insight into the mechanism for recognizing
      substrates with alpha-(1,6) glycosidic linkages.
AB  - Thermoactinomyces vulgaris R-47 alpha-amylase 1 (TVAI) has unique hydrolyzing
      activities for pullulan with sequence repeats of alpha-(1,4), alpha-(1,4), and
      alpha-(1,6) glycosidic linkages, as well as for starch. TVAI mainly hydrolyzes
      alpha-(1,4) glycosidic linkages to produce a panose, but it also hydrolyzes alpha
      (1,6) glycosidic linkages with a lesser efficiency. X-ray structures of three
      complexes comprising an inactive mutant TVAI (D356N or D356N/E396Q) and a
      pullulan model oligosaccharide (P2; [Glc-alpha-(1,6)-Glc-alpha-(1,4)-Glc-alpha
      (1,4)]2 or P5; [Glc-alpha-(1,6)-Glc-alpha-(1,4)-Glc-alpha-(1,4)]5) were
      determined. The complex D356N/P2 is a mimic of the enzyme/product complex in the
      main catalytic reaction of TVAI, and a structural comparison with Aspergillus
      oryzaealpha-amylase showed that the (-) subsites of TVAI are responsible for
      recognizing both starch and pullulan. D356N/E396Q/P2 and D356N/E396Q/P5 provided
      models of the enzyme/substrate complex recognizing the alpha-(1,6) glycosidic
      linkage at the hydrolyzing site. They showed that only subsites -1 and -2 at the
      nonreducing end of TVAI are effective in the hydrolysis of alpha-(1,6) glycosidic
      linkages, leading to weak interactions between substrates and the enzyme. Domain
      N of TVAI is a starch-binding domain acting as an anchor in the catalytic
      reaction of the enzyme. In this study, additional substrates were also found to
      bind to domain N, suggesting that domain N also functions as a pullulan-binding
      domain.

PMID- 16302978
TI  - Interaction of gymnemic acid with cyclodextrins analyzed by isothermal titration
      calorimetry, NMR and dynamic light scattering.
AB  - The physiological phenomenon that the antisweet taste effect of gymnemic acid
      (GA) is diminished by application of gamma-cyclodextrin (gamma-CD) to the mouth
      was evaluated at the molecular level using isothermal titration calorimetry, NMR
      and dynamic light scattering. These analyses showed that GA specifically binds to
      gamma-CD. Thermodynamic analysis using isothermal titration calorimetry revealed
      that the association constant of GA and gamma-CD is 10(5)-10(6) m(-1) with
      favorable enthalpy and entropy changes. The heat capacity change was negative and
      large, despite the change in accessible surface area upon binding being small.
      These thermodynamics indicate that the binding is dominated by hydrophobic
      interactions, which is in agreement with inclusion complex formation of gamma-CD.
      In addition, NMR measurements showed that in solution the spectra of GA are broad
      and sharpened by the addition of gamma-CD, indicating that unbound GA is in a
      water-soluble aggregate that is dispersed when it forms a complex with gamma-CD.
      Dynamic light scattering showed that the average diameter of unbound GA is > 30
      nm and that of GA and gamma-CD complex is 2.2 nm, similar to unbound gamma-CD,
      supporting the aggregate property of GA and the inclusion complexation of GA by
      gamma-CD.

PMID- 16302979
TI  - Studies on the interaction of Nile red with horseradish peroxidase in solution.
AB  - The interaction of an extrinsic probe (Nile red) with an enzyme (horseradish
      peroxidase) in solution was investigated using fluorescence techniques. Nile red
      fluorescence is very environmentally sensitive and the presence of domains of
      differing polarity within the enzyme was ascertained by the decomposition of the
      Nile red emission spectrum. Further evidence for the position of the probe inside
      the enzyme was obtained from a molecular modeling study. A decrease in the
      emission intensity of the dye during incubation with horseradish peroxidase was
      explained by the occurrence of resonance energy transfer between the Nile red and
      the heme group in the enzyme. This was supported by a calculation of the critical
      transfer distance and a comparison of the fluorescence intensity of the dye in
      both the holo- and apo-enzyme. These data were then applied to the study of the
      effect of temperature on the structure of the enzyme, where changes in
      conformation were elucidated.

PMID- 16302980
TI  - Functional analysis of disease-causing mutations in human UDP-galactose 4
      epimerase.
AB  - UDP-galactose 4-epimerase (GALE, EC 5.1.3.2) catalyses the interconversion of UDP
      glucose and UDP-galactose. Point mutations in this enzyme are associated with the
      genetic disease, type III galactosemia, which exists in two forms - a milder, or
      peripheral, form and a more severe, or generalized, form. Recombinant wild-type
      GALE, and nine disease-causing mutations, have all been expressed in, and
      purified from, Escherichia coli in soluble, active forms. Two of the mutations
      (N34S and G319E) display essentially wild-type kinetics. The remainder (G90E,
      V94M, D103G, L183P, K257R, L313M and R335H) are all impaired in turnover number
      (k cat) and specificity constant (k cat/Km), with G90E and V94M (which is
      associated with the generalized form of galactosemia) being the most affected.
      None of the mutations results in a greater than threefold change in the Michaelis
      constant (Km). Protein-protein crosslinking suggests that none of the mutants are
      impaired in homodimer formation. The L183P mutation suffers from severe
      proteolytic degradation during expression and purification. N34S, G90E and D103G
      all show increased susceptibility to digestion in limited proteolysis
      experiments. Therefore, it is suggested that reduced catalytic efficiency and
      increased proteolytic susceptibility of GALE are causative factors in type III
      galactosemia. Furthermore, there is an approximate correlation between the
      severity of these defects in the protein structure and function, and the symptoms
      observed in patients.

PMID- 16302981
TI  - Inhibition of proinflammatory cytokine expression by NF-kappaB (p65) antisense
      oligonucleotide in Helicobacter pylori-infected mice.
AB  - BACKGROUND: Helicobacter pylori induces the expression of proinflammatory
      cytokines in vitro by activating nuclear factor-kappaB, a transcriptional
      regulator. However, it has not been clarified whether H. pylori-induced
      proinflammatory cytokines are also mediated through nuclear factor-kappaB in
      vivo. The aim of this study was to evaluate the role of nuclear factor-kappaB on
      the expressions of proinflammatory cytokines in H. pylori-infected mice.
      MATERIALS AND METHODS: We evaluated nuclear factor-kappaB (p65) activation in the
      H. pylori-infected gastric mucosa of mice by immunofluorescent staining using
      antip65 polyclonal antibody, and the expressions of proinflammatory cytokines
      with inhibition of nuclear factor-kappaB pathway by using phosphorothioate
      antisense and sense oligonucleotide against the nuclear factor-kappaB (p65).
      RESULTS: In the H. pylori-infected gastric mucosa of mice, immunofluorescent
      staining using antip65 polyclonal antibody showed nuclear factor-kappaB (p65)
      activation, which was particularly localized to epithelial cells. Tumor necrosis
      factor-alpha and interleukin-1beta concentrations in gastric mucosa by enzyme
      linked immunosorbent assay (ELISA) were elevated in the infected group versus the
      uninfected group. Pretreatment with nuclear factor-kappaB (p65) antisense
      oligonucleotide inhibited the activation of nuclear factor-kappaB and the
      expressions of tumor necrosis factor-alpha and interleukin-1beta in H. pylori
      infected gastric mucosa. Sense oligonucleotide did not influence on the
      expression of proinflammatory cytokines. CONCLUSIONS: H. pylori infection was
      found to activate the expressions of proinflammatory cytokines via nuclear factor
      kappaB in vivo, and this may play an important role in the initiation of H.
      pylori-induced gastric inflammation.

PMID- 16302982
TI  - A novel mechanism of autolysis in Helicobacter pylori: possible involvement of
      peptidergic substances.
AB  - BACKGROUND: Helicobacter pylori survival in a hostile acidic environment is known
      to be caused by its production of urease, which is not released by known
      secretion pathways. It has been proposed that H. pylori cells undergo spontaneous
      autolysis during cultivation and that urease becomes surface-associated only
      concomitant with bacterial autolysis. The aim of this study was to elucidate
      mechanisms by which H. pylori cells undergo autolysis during cultivation.
      MATERIALS AND METHODS: Autolysis of H. pylori KZ109 cells was estimated by
      measuring the turbidity of the culture, by detection of cytoplasmic protein
      release into the culture supernatant and by scanning electron microscopic
      observation of H. pylori cells during cultivation. An autolysis-inducing factor
      (AIF) was partially purified from the culture supernatant by a partition method
      using ethyl acetate. RESULTS: Bacterial turbidity of KZ109 cells was drastically
      decreased after late-log phase accompanying release of urease and HspB into the
      extracellular space. Concomitantly, cell lytic activity was detected in the
      culture supernatant. Scanning electron microscopic observation suggested that
      partially purified AIF induced cell lysis. It was also shown that the AIF is
      different from other autolytic enzymes or substances so far reported.
      CONCLUSIONS: This study demonstrated the presence of the peptidergic autolytic
      substances in the culture supernatant of H. pylori KZ109 cells. The results of
      this study should be useful for further studies aimed at elucidation of the
      strategy of survival of H. pylori in the gastric environment and elucidation of
      the mechanisms of pathogenesis induced by H. pylori.

PMID- 16302983
TI  - Lower prevalence of Helicobacter pylori infection with vacAs1a, cagA-positive,
      and babA2-positive genotype in erosive reflux esophagitis disease.
AB  - BACKGROUND: Increased prevalence of esophagitis has been recognized in the West.
      Helicobacter pylori infection, particularly virulent strains, is proposed as a
      protective factor against the development of gastroesophageal reflux disease. To
      evaluate the relationship of reflux esophagitis with virulent H. pylori
      infection, we studied the prevalence of reflux esophagitis among H. pylori
      infected and -uninfected patients and the genotype of isolates in Taiwan.
      METHODS: Patients who had routine physical examination were investigated. The
      severity of esophagitis was evaluated using the Los Angeles grading system. H.
      pylori status was assessed by histology, rapid urease test, and bacterial
      culture. Genotyping of vacA, cagA, and babA2 was determined by polymerase chain
      reaction (PCR). Risk factors for severe esophagitis were evaluated. RESULTS:
      Reflux esophagitis was found in 21.2% of 1622 patients. The prevalence of H.
      pylori infection was found in 33.0% of 276 patients with reflux esophagitis
      compared with 67.5% of 378 patients with normal esophagus (p < .001). Esophagitis
      occurred in a significantly lower rate among H. pylori-positive patients with
      peptic ulcer than those without peptic ulcer. cagA, babA2, and vacAs1a were
      detected in 100% of 143 isolates. Factors that predicted severe esophagitis
      included age, gender, and hiatus hernia but not H. pylori infection. CONCLUSIONS:
      Our study suggests significantly lower incidence of H. pylori infection with the
      triple-positive virulent genotype in patients with reflux esophagitis in Taiwan.

PMID- 16302984
TI  - Effect of long-term Helicobacter felis infection in a mouse model of
      streptozotocin-induced diabetes.
AB  - BACKGROUND: We previously REPORTED that mice with diabetes and short-term
      Helicobacter felis infection had an increase in glycated hemoglobin (HbA1c). Here
      we report the effect of long-term infection. MATERIALS AND METHODS: Six-week-old
      C57BL/6 mice were injected with streptozotocin to induce diabetes and started on
      daily insulin. Following streptozotocin injection, animals were paired according
      to their HbA1c values and randomized to orally receive either H. felis or culture
      medium alone. Weight and HbA1c were monitored monthly for 6 months. RESULTS:
      Thirty animals corresponding to 15 pairs were included in the study. H. felis
      infected diabetic mice developed significantly more gastritis than uninfected
      animals. Sixteen mice died during the observation period. As compared to
      uninfected animals, infected mice died more frequently (40% versus 67%, p = .14)
      and earlier (160 versus 61 days, p = .20); both variables combined showed that H.
      felis infection significantly decreased the chances of survival during the study
      period (p = .045). In addition, infected mice showed a trend for higher increase
      in their HbA1c (0.97 +/- 2.5% versus - 0.22 +/- 3.0%; p = .21) and lower weight
      gain (2.0 +/- 3.4 g versus 2.9 +/- 2.0 g; p = .15) than uninfected mice.
      CONCLUSION: Long-term H. felis infection had a deleterious effect in mice with
      streptozotocin-induced diabetes resulting in increased mortality. If the same
      phenomenon occurs in humans this could lead to interventions to improve the long
      term outcome of patients with diabetes.

PMID- 16302985
TI  - Multiple displacement amplification of isolated DNA from human gallstones:
      molecular identification of Helicobacter DNA by means of 16S rDNA-based
      pyrosequencing analysis.
AB  - BACKGROUND: Molecular typing of Helicobacter spp. in clinical biopsy specimens
      has become increasingly important. By means of nested polymerase chain reaction
      (PCR) amplification and Southern blot analysis of the PCR amplicons, we have
      shown that Helicobacter spp. DNA is present in human gallstones. In this study we
      have investigated the possibility of using multiple displacement amplification
      (MDA) of isolated gallstone DNA and pyrosequencing analysis for the molecular
      identification of Helicobacter spp. MATERIALS AND METHODS: DNA isolated from the
      nucleus of 33 human gallstones and one control strain were used in a MDA assay.
      Subsequently, pyrosequencing analysis was performed either directly on MDA-DNA
      using primers flanking the Helicobacter spp. 16S rDNA variable V3 region or on
      PCR amplicons derived from broad-range primers flanking the 16S rDNA variable V3,
      V4, and V9 regions. RESULTS: Pyrosequencing analysis of 16S rDNA derived from MDA
      DNA revealed that Helicobacter spp.-like DNA was present in 25 of 33
      (approximately 76%) gallstones. Using an H. pylori-specific Southern blot
      analysis, Helicobacter spp.-like DNA was present in 20 of 33 [approximately 61%]
      of the gallstones. Using MDA-DNA directly in pyrosequencing analysis,
      Helicobacter spp.-like DNA was present in 13 of 33 [approximately 39%]
      gallstones. CONCLUSIONS: We conclude that multiple displacement amplification
      combined with pyrosequencing enables a rapid and accurate molecular typing of
      Helicobacter spp. from small and precious biopsy specimens.

PMID- 16302986
TI  - No correlation of babA2 with vacA and cagA genotypes of Helicobacter pylori and
      grading of gastritis from peptic ulcer disease patients in Brazil.
AB  - BACKGROUND: The babA2 gene, which encodes a blood-group antigen-binding adhesin
      that mediates attachment of Helicobacter pylori to human Lewis(b) antigens on
      gastric epithelial cells, has been associated with a higher risk of peptic ulcer
      and gastric cancer. The purpose of this study was to ascertain the frequency of
      babA2 genotype in H. pylori strains of patients with peptic ulcer and to
      correlate with other virulence factors. MATERIALS AND METHODS: vacA, cagA, and
      babA2 genotypes of H. pylori were determined by using polymerase chain reaction
      (PCR). DNA was extracted from positive urease test gastric samples of 150
      patients with peptic ulcer. Antrum and corpus biopsies were taken for histologic
      examination according to the updated Sydney system classification. RESULTS: babA2
      genotype was present in 104 (69.3%) and cagA in 113 (75.3%) gastric samples. No
      significant correlation was observed between babA2 and vacAs1 genotype or between
      babA2 and cagA status. The correlation of vacAs1 genotype with positive cagA was
      statistically significant ( p < .001). The babA2-positive strain was more
      frequently found from the gastric samples of men, than of women (p = .01).
      Strains harboring cagA, vacAs1, and babA2 genotypes had no association to the
      grading of gastritis, presence of glandular atrophy, or intestinal metaplasia.
      The simultaneous presence of cagA, vacAs1, and babA2 was found in 32.6% of the H.
      pylori strains. CONCLUSIONS: babA2 genotype is frequently found in H. pylori
      strains from peptic ulcer disease in Brazil, although it has no significant
      correlation to the worsening of the gastritis and to other virulence markers such
      as vacAs1 and cagA.

PMID- 16302987
TI  - Asymptomatic Helicobacter pylori infection increases asymmetric dimethylarginine
      levels in healthy subjects.
AB  - BACKGROUND: Chronic infections have been demonstrated to be early factors of
      atherosclerosis and cardiovascular diseases, and their relevance increases when
      they are caused by agents with extremely broad spectrum of disease outcome such
      as Helicobacter pylori. The consequent endothelial impairment leads to a reduced
      bioavailability of nitric oxide. Increasing evidences have pointed out that the
      endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine,
      defined as a risk factor for cardiovascular disease, may increase in infections
      and plays an important role impairing the vascular functions of the endothelium.
      Starting from these findings, we aim to investigate whether H. pylori may affect
      asymmetric dimethylarginine levels. MATERIALS AND METHODS: The study was carried
      out on a group of 186 subjects (age 46.2 +/- 14.9 years). We evaluated asymmetric
      dimethylarginine, symmetric dimethylarginine, L-arginine, presence of H. pylori
      by 13C-urea breath test, and the main parameters of glyco and lipo metabolic
      balance. RESULTS: Increased levels of asymmetric dimethylarginine were found in
      H. pylori-positive subjects with respect to H. pylori-negative subjects (0.46 x/
      / 1.13 versus 0.42 x/ / 1.23 mol/l, p < .001, respectively). No differences were
      detected in L-arginine levels between the two groups. Multiple regression
      analysis performed in H. pylori-positive subjects and H. pylori-negative subjects
      showed profound differences in the variables related to asymmetric
      dimethylarginine (R2 = 66.9%, p < .01 versus 34.3%, p < .01, respectively) and
      symmetric dimethylarginine (R2 = 39.2%, p < .01 versus 20.6%, p = .09,
      respectively) levels. CONCLUSIONS: Our data clearly demonstrate that H. pylori
      infection increases asymmetric dimethylarginine levels. Moreover, this infection
      causes a profound metabolic modification that alters the role of the known
      determinants of asymmetric dimethylarginine levels. We conclude that H. pylori
      infection must be taken into account as a cause of increased asymmetric
      dimethylarginine levels and that the eradication of H. pylori may therefore lead
      to a decrease in asymmetric dimethylarginine levels, which is a further reason
      for the reduction of the risk for cardiovascular disease in this large portion of
      population.

PMID- 16302988
TI  - 13C-urea breath test to assess Helicobacter pylori bacterial load.
AB  - BACKGROUND: Some authors have reported, using different protocols, that 13C-urea
      breath test (13C-UBT) is capable of assessing the intragastric Helicobacter
      pylori bacterial load, whereas others have not confirmed these data. Our aim is
      to evaluate the correlation between 13C-UBT values and H. pylori bacterial load.
      MATERIALS AND METHODS: One hundred ninety-two patients diagnosed H. pylori
      positive by rapid urease test, histology, and 13C-UBT were enrolled. H. pylori
      bacterial load (H. pylori score) and gastritis activity (activity score) were
      evaluated according to the Updated Sydney System. 13C-UBT was performed according
      to the European Standard Protocol. Breath samples were obtained every 10 minutes
      for 60 minutes in 52 patients and at 30 minutes (T30) in 140 patients and
      analyzed by mass spectrometry. RESULTS: At T30, mean +/- SD excess delta 13CO2
      excretion was 17.4 +/- 1.1, 29.9 +/- 2.2, and 48.7 +/- 4.8 in patients with H.
      pylori scores 1, 2, and 3, respectively. This difference was statistically
      significant: H. pylori score 1 versus 2, p < .005; score 1 versus 3, p < .05;
      score 2 versus 3, p < .05. A significant positive correlation (G = 0.59) was
      found between H. pylori score and activity score of chronic gastritis. At T40 and
      T50 significant correlation between mean excess delta 13CO2 excretion and
      bacterial load was achieved only in patients with H. pylori scores 1 and 3.
      CONCLUSIONS: 13C-UBT European Standard Protocol values correlate with H. pylori
      bacterial load and the activity of gastritis at T30 breath sampling time.

PMID- 16302989
TI  - Major influence of oxygen supply on 13CO2:12CO2 ratio measurement by
      nondispersive isotope-selective infrared spectroscopy.
AB  - BACKGROUND: The nondispersive isotope-selective infrared spectroscopy (NDIRS) is
      a valid method for the measurement of the 13CO2:12CO2 ratio in breath samples.
      Methodical influences have to be considered to obtain valid results. AIM: To
      evaluate the effect of oxygen supply to patients on the measurement of 13C:12C
      ratio in breath samples by NDIRS. METHODS: Breath samples of 26 healthy
      volunteers were taken before, immediately after, and 5 minutes after inhalation
      of 100% oxygen via a continuous positive air pressure (CPAP) mask. Analysis of
      breath samples was performed by NDIRS. RESULTS: Delta per thousand before oxygen
      inhalation was -25.8 +/- 0.2. Immediately after 5 minutes of 100% oxygen
      inhalation, delta per thousand increased to -14.8 +/- 0.5 (delta over baseline
      [DOB] 11.0 +/- 0.4) and after additional 5 minutes of room air inhalation, delta
      per thousand normalized to -25.6 +/- 0.2 (DOB 0.2 +/- 0.1). CONCLUSIONS: Oxygen
      supply to patients and, therefore, changes in gas composition in breath samples
      clearly influence 13CO2 measurement by NDIRS. This has to be taken into account
      in the clinical setting. Thus, oxygen supply during measurement of exhaled 13CO2
      by NDIRS has to be avoided or maintained at a strictly constant level.

PMID- 16302990
TI  - Is there a possible relation between atrophic gastritis and premature
      atherosclerosis?
AB  - BACKGROUND: In this study, we have aimed to show the possible relation between
      atrophic gastritis and premature atherosclerosis via hyperhomocysteinemia.
      MATERIALS AND METHODS: Thirty-four patients with atrophic gastritis were enrolled
      to the study. The control group consisted of 35 patients with non-atrophic
      gastritis. Classical cardiovascular disease risk factors did not significantly
      differ between atrophic gastritis and control subjects. The presence and degree
      of atrophic gastritis were assessed histologically and Helicobacter pylori
      infection was determined by both histologic and serologic methods. Body mass
      index was measured by standard technique blood fasting glucose, serum creatinine,
      total cholesterol, triglyceride, low-density lipoprotein cholesterol, high
      density lipoprotein cholesterol, vitamin B12, folic acid, and homocysteine levels
      were measured by biochemical methods. Carotid intima-media thickness was measured
      by B-mode ultrasonography to examine the premature atherosclerosis. RESULTS:
      Plasma vitamin B12 levels were significantly lower (p = .00) and homocysteine
      levels were significantly higher (p = .01) in the atrophic gastritis group. There
      was no statistically significant difference in plasma folic acid levels between
      the two groups (p = .728). Carotid intima-media thickness was higher in the
      atrophic gastritis group than in the control group (0.516 mm versus 0.465 mm),
      but this difference did not show any statistical significance (p = .062).
      CONCLUSION: Our results showed that atrophic gastritis may cause
      hyperhomocysteinemia, which is an independent risk factor for atherosclerosis and
      cardiovascular diseases. However, when compared with controls, carotid intima
      media thickness of the atrophic gastritis patients was found to be higher but did
      not reach statistically significant levels.

PMID- 16302991
TI  - Methodology and transport medium for collection of Helicobacter pylori on a
      string test in remote locations.
AB  - BACKGROUND: Helicobacter pylori can be isolated from patients using the string
      test but contaminating oral and nasopharyngeal microflora need to be suppressed
      by rapid plating out onto selective culture media. Recently, use of this
      diagnostic method was enhanced by using a novel transport medium to collect
      specimens from subjects in a remote Australian clinic over 1300 km from the
      laboratory. METHODS: Retrieved string tests were transported to the laboratory in
      chilled polystyrene boxes in 5 ml screw-cap bottles with 3 ml of a brain heart
      infusion broth plus antibiotics. These were 20 g/ml vancomycin, 10 g/ml
      trimethoprim, 10 g/ml cefsulodin, and 10 g/ml amphotericin B. A comparison was
      made between subjects who gargled with a chlorhexidine mouthwash before
      swallowing the string test and those who did not. RESULTS: Forty-five urea breath
      test-positive subjects were tested and H. pylori was isolated from 34 of them.
      Successful culture was achieved from string tests that were in transit for up to
      29 hours and where the maximum temperature in the transport box was 14 degrees C.
      The additional use of a mouthwash had a marked effect on the isolation rate. H.
      pylori was cultured from 75% of subjects who gargled but only from 39% who did
      not. CONCLUSIONS: This methodology and transport medium can broaden the use of
      the string test to more remote geographic areas where endoscopy is not feasible
      so that H. pylori isolates may still be obtained for diagnostic and epidemiologic
      studies. The value of this promising methodology of collection and transport
      should be assessed in a controlled study.

PMID- 16302992
TI  - Dendritic cells: tools and targets for transplant tolerance.
AB  - Our knowledge of the role of dendritic cells (DC) in the generation and
      maintenance of T-cell tolerance has expanded rapidly and is now a key area of
      research in basic and applied DC biology. This minireview highlights recent
      developments in the field that are leading to new avenues for exploiting DC in
      the promotion of transplant tolerance.

PMID- 16302993
TI  - Metabolomics: the principles and potential applications to transplantation.
AB  - This review provides a summary of the applications and potential applications of
      metabolite profiling (i.e. metabolomics) in monitoring organ transplants. While
      the concept of metabolomics is relatively new to organ transplantation, the idea
      of measuring metabolites as a quick, noninvasive probe of organ function is not.
      Indeed, metabolite measurements of serum creatinine have long been used to assess
      pre- and post-operative organ function. Over the past 10 years, a number of
      lesser-known, organ-specific metabolites have also been shown to be good
      diagnostic indicators of both organ function and viability. In general,
      metabolomics offers a complementary picture to what can be revealed via
      techniques based on genomics, proteomics or histology. Because metabolic changes
      typically happen within seconds or minutes after an 'event', whereas some
      transcript, protein abundance or tissue changes may take place over days or
      weeks, metabolomic measurements may offer a particularly useful and inexpensive
      diagnostic tool to monitor donor organ viability or to detect organ rejection.
      The excitement associated with metabolomics, however, must be tempered by the
      fact that the technology for rapid metabolite identification is still in its
      infancy, and that metabolites are but one part of a very complex picture
      pertaining to organ function.

PMID- 16302994
TI  - Differing mechanisms of early and late B cell hyporesponsiveness induced by mixed
      chimerism.
AB  - Mixed hematopoietic chimerism induced via nonmyeloablative bone marrow
      transplantation (BMT) leads to unresponsiveness of anti-Gal alpha1,3Gal
      beta1,4G1cNAc (Gal) natural antibody (NAb)-producing cells in alpha1,3
      galactosyltransferase deficient (GalT(-/-)) mice. We analyzed the mechanisms of
      anti-Gal-producing B cell unresponsiveness induced by Gal(+/+) BMT. C57BL/6 (B6)
      GalT(-/-) mice received 3Gy whole-body irradiation and BMT from B6-CD45 congenic
      mice. BMT led to marked reductions in serum anti-Gal IgM levels and in the
      numbers of splenic anti-Gal-producing cells by 2 weeks post-BMT. B cells with
      anti-Gal Ig receptors were present in the spleens of 2-week but not 12-week
      chimeras. In vitro studies and adoptive transfer studies using B6 GalT(-/-)B cell
      deficient recipients showed that B cell hyporesponsiveness to Gal at 2 weeks, but
      not 12 weeks, depended on persistent Gal antigen. Thus, pre-existing B-1 cells
      are anergic when there is continuous exposure to Gal, whereas long-term
      unresponsiveness does not require persistent antigen, implicating clonal deletion
      and/or receptor editing. These results have implications for the potential use of
      mixed hematopioetic chimerism as an approach to performing organ transplantation
      in recipients with pre-existing anti-donor IgM antibodies.

PMID- 16302995
TI  - Intra-ductal glutamine administration reduces oxidative injury during human
      pancreatic islet isolation.
AB  - Oxidative stress during islet isolation induces a cascade of events injuring
      islets and hampering islet engraftment. This study evaluated islet isolation and
      transplantation outcomes after intra-ductal glutamine administration. Human
      pancreata deemed unsuitable for pancreas or islet transplantation were treated
      with either a 5 mM solution of l-glutamine (n = 6) or collagenase enzyme alone (n
      = 6) through the main pancreatic duct. Islet yield, viability, in vitro function;
      markers of oxidative stress [malondialdehyde (MDA) and Glutathione (GSH)] and
      apoptosis were assessed. Islet yields were significantly increased in the
      glutamine group compared to controls (318, 559 +/- 25, 800 vs. 165, 582 +/- 39,
      944 mean +/- SEM, p < 0.01). The amount of apoptotic cells per islet was smaller
      in the glutamine group than the control. The percentage of nude mice rendered
      normoglycemic with glutamine-treated islets was higher than the controls (83% n =
      10/12 vs. 26% n = 6/23; p < 0.01), and the time to reach normoglycemia was
      decreased in the glutamine group (1.83 +/- 0.4 vs. 7.3 +/- 3 days; p < 0.01).
      Glutamine administration increased GSH levels (7.6 +/- 1.7 nmol/mg protein vs.
      4.03 +/- 0.5 in control, p < 0.05) and reduced lipid-peroxidation (MDA 2.45 +/-
      0.7 nmol/mg of protein vs. 6.54 +/- 1.7 in control; p < 0.05). We conclude that
      intra-ductal administration of glutamine reduces oxidative injury and apoptosis
      and improves islet yield and islet graft function after transplantation.

PMID- 16302996
TI  - Primary alloproliferative TH1 response induced by immature plasmacytoid dendritic
      cells in collaboration with myeloid DCs.
AB  - The role played by dendritic cell (DC) subsets in the immune response to
      alloantigens is not well defined. In vitro experiments have extensively shown
      that freshly isolated myeloid (M)DCs induce a strong T lymphocyte proliferation
      whereas plasmacytoid (P)DCs do not, unless activated by CD40 ligation. The aim of
      these studies was to explore whether the interplay among PDCs, MDCs and T cells
      modulates alloresponse. Freshly isolated MDCs and PDCs were merged in different
      proportions and used as antigen presenting cells (APCs) in mixed lymphocyte
      cultures (MLC). As described, isolated PDCs only induced a mild alloresponse,
      while MDCs were potent inducers of alloproliferation. Unexpectedly, when PDCs
      were merged with even low numbers of MDCs (down to 100 cells) and used as APCs, a
      potent Th1 cell proliferation was detected. Survival and maturation of PDCs was
      increased in these MLC conditions, which could partially explain the magnitude of
      the T-cell response. Interestingly, the proportion of IFNgamma-producing cells
      generated in such cultures was higher compared to MDC-stimulated cultures. These
      data suggest that the interaction between both DC subsets is determinant to
      generate a potent Th1 response, at least in an allogeneic situation, and may be
      relevant to the outcome of allogeneic stem cell transplantation.

PMID- 16302997
TI  - Mechanisms of everolimus-induced glomerulosclerosis after glomerular injury in
      the rat.
AB  - Despite the lack of nephrotoxicity, adverse effects of the new antiproliferative
      immunosuppressant everolimus have been reported. By varying time point and dose
      of everolimus treatment as well as the degree of glomerular injury, the specific
      conditions and potential mechanisms leading to adverse actions in the anti-Thy1
      model have been determined. Only the combination of early and high-dose
      everolimus treatment (1-3 mg/kg bw) with a severe glomerular lesion ('full-dose'
      anti-Thy1 model) caused adverse effects with a high mortality rate, progressive
      apoptosis, crescent formation and glomerulosclerosis. In contrast, either later
      start or low-dose (0.3 mg/kg bw) therapy or treatment of a less severe lesion
      ('reduced dose' anti-Thy1 model) appeared to be relatively safe for the
      glomerular architecture. The adverse effects of everolimus were linked to its
      marked inhibition of endothelial cell, but not necessarily mesangial cell
      proliferation. In addition, everolimus markedly inhibited the angiogenic cytokine
      vascular endothelial growth factor in nephritic glomeruli in vivo. These
      experimental results suggest special caution regarding the use of everolimus in
      all situations of severe glomerular cell injury requiring extensive capillary
      repair, where at least adaption to a low dose needs to be considered.

PMID- 16302998
TI  - Mannitol but not dantrolene prevents myocardial dysfunction following intra
      cranial hypertension in rats.
AB  - Cardiac complications stemming from intra-cranial hypertension may result from
      impaired intra-cellular Ca(2+) homeostasis. The aim of this study was to examine
      the effects of dantrolene, a blocker of sarcoplasmic reticulum (SR) Ca(2+)
      release, on myocardial dysfunction associated with intra-cranial hypertension in
      rats. Dantrolene (10 mg) with and without 15% mannitol was administered to
      halothane-anesthetized rats prior to induction of intra-cranial hypertension by
      subdural balloon inflation. Its effects were compared to 3% and 15% mannitol and
      5% Pentaspan. Dantrolene with mannitol or 15% mannitol alone prevented the
      transient intra-cranial hypertension-induced hyperdynamic response and ensuing
      circulatory collapse that was found in animals pre-treated with 3% mannitol
      solution or pentaspan. Moreover, hemodynamic function was preserved irrespective
      of TnI cleavage. However, only animals treated with high dose 15% mannitol
      exhibited lower lipid peroxidation content in the heart. In contrast, pre
      treatment with dantrolene alone did not prevent the cardiac complications
      associated with intra-cranial hypertension. In conclusion, 15% mannitol
      attenuated the cardiopulmonary complications associated with intra-cranial
      hypertension. Dantrolene without mannitol was without effect. Since mannitol
      exhibits free radical scavenging properties, protection could be the result of a
      decrease in oxidative stress after intra-cranial hypertension.

PMID- 16302999
TI  - Peritubular capillary damage in acute humoral rejection: an ultrastructural study
      on human renal allografts.
AB  - The ultrastructural features of peritubular capillary (PC) damage was studied in
      12 kidney allografts with acute humoral rejection (AHR). AHR manifested in
      diffuse linear PC staining for C4d, and histology consistent with Banff grade III
      in 7 recipients and Banff grade II in 5. Allografts with acute tubular necrosis
      served as controls. First biopsies (post-transplantation day 16.2 +/- 2.2): The
      intra-capillary exudate comprised monocytes (59%), polymorphonuclears (14%),
      lymphocytes (12%) and not otherwise specified mononuclears (15%). Three patterns
      of focal PC endothelial injury were observed: lysis, an increased rate of
      apoptosis and fragmentation. No correlation was found between the respective
      damage types and the inflammatory cell types or the Banff grades. Controls
      revealed endothelial swelling, detachment from basement membrane and
      fragmentation. Follow-up biopsies: Monocytes transformed into macrophages intra
      luminally. The reparative changes comprised endothelial cytoplasmic protrusions,
      binucleated endothelial cells and capillary sprouts. Early transplant
      capillaropathy and transplant glomerulopathy were noted in 2 recipients.
      Literature data indicate that lysis is mediated by anti-HLA alloantibodies;
      apoptosis, demonstrated first in the present study, may be induced by non-HLA
      type anti-endothelial antibodies. Fragmentation is caused by ischemia. Ongoing
      endothelial injury leads to transplant capillaropathy and transplant
      glomerulopathy, the characteristic lesions of chronic rejection.

PMID- 16303000
TI  - Glomerular size in early protocol biopsies is associated with graft outcome.
AB  - Long-term consequences of glomerular enlargement after transplantation are not
      well understood. The aim is to evaluate the relationship between glomerular
      volume (Vg) estimated in protocol biopsies, graft function and graft survival. Vg
      and Banff chronic damage score were evaluated in protocol biopsies at 4 months.
      Creatinine clearance (CrCl) was estimated by the Cockroft-Gault formula. Vg
      estimated in 144 patients was 4.8 +/- 2.0 x 10(6)mu(3). It was associated with
      donor age (r = 0.23, p < 0.01), recipient body mass index (r = 0.17, p = 0.04),
      delayed graft function (Vg = 5.9 +/- 2.3 vs. 4.6 +/- 1.9 x 10(6)mu(3), p < 0.01)
      and CrCl (r = 0.17, p = 0.04). The best cutoff of Vg, Banff chronic damage score
      and CrCl was determined by Cox regression analysis, being 5.0 x 10(6)mu(3) for Vg
      (relative risk (RR): 2.4, 95% confidence interval (CI): 1.03-5.6), >2 for chronic
      damage score (RR: 3.4, 95% CI: 1.03-8.9) and 60 mL/min for CrCl (RR: 3.5, 95% CI:
      1.04-11.9). These variables were independent predictors of death-censored graft
      survival. According to Vg and CrCl, four groups of patients were defined.
      Patients with small glomeruli and high CrCl had a 95% graft survival while
      patients with large glomeruli and low CrCl had a 45% graft survival at 15 years
      (p < 0.01). Large glomerular volume, high Banff chronic score and poor early
      renal function in stable grafts are independently associated with death-censored
      graft survival.

PMID- 16303001
TI  - Molecular evaluation of BK polyomavirus nephropathy.
AB  - Understanding at a molecular level, the immunologic response of polyomavirus
      nephropathy (PVN), a critical cause of kidney graft loss, could lead to new
      targets for treatment and diagnosis. We undertook a transcriptional evaluation of
      kidney allograft biopsies from recipients with PVN or acute rejection (AR), as
      well as from recipients with stable allograft function (SF). In both the PVN and
      AR groups, Banff histologic scores and immunohistochemical analysis of
      inflammatory infiltrates were similar. Despite their different etiologies, the
      transcriptional profiles of PVN and AR were remarkably similar. However,
      transcription of genes previously linked to AR including CD8 (65.9 +/- 18.8) and
      related molecules IFN-gamma(55.1 +/- 17.0), CXCR3 (49.9 +/- 12.8) and perforin
      (153.8 +/- 50.4) were significantly higher in PVN compared to AR (30.9 +/- 2.0,
      14.0 +/- 7.3, 12.1 +/- 7.3 and 15.6 +/- 3.8-fold, respectively; p < 0.01).
      Importantly, transcription of molecules associated with graft fibrosis including
      matrix collagens, TGFbeta, MMP2 and 9, as well as markers of epithelial
      mesenchymal transformation (EMT) were significantly higher in PVN than AR. Thus,
      renal allografts with PVN transcribe proinflammatory genes equal in character and
      larger in magnitude to that seen during acute cellular rejection. BK infection
      creates a transcriptional microenvironment that promotes graft fibrosis. These
      findings provide new insights into the intrarenal inflammation of BK infection
      that promotes graft loss.

PMID- 16303002
TI  - Ganciclovir and acyclovir reduce the risk of post-transplant lymphoproliferative
      disorder in renal transplant recipients.
AB  - Given its association with Epstein-Barr virus (EBV), there is considerable
      interest in assessing the impact of prophylactic anti-viral therapy on post
      transplant lymphoproliferative disorder (PTLD). A recently completed multi center
      case-control study assessed the impact of immunosuppressive therapy on PTLD risk
      among renal transplant patients and collected information on the use of anti
      viral therapy. Biopsy-confirmed PTLD cases (n = 100) were matched to 375 controls
      by center, date of transplant, and age. Data were collected on immunosuppression
      and rejection therapies, demographics, pre-transplant viral status, number of
      rejections, and anti-viral use. With adjustment for known risk factors,
      prophylactic anti-viral use was associated with up to 83% reduction in the risk
      of PTLD, depending on the anti-viral agent. These results were stronger for the
      first year post-transplant. For every 30 days of ganciclovir treatment, risk of
      PTLD during the first year was lower by 38% (Odds Ratio [OR]= 0.62; 95%
      confidence interval [CI]= 0.38-1.0); acyclovir effects were less striking (OR =
      0.83; 95% CI = 0.59-1.16). Anti-viral therapy appears to play a role in reducing
      the risk of PTLD in renal transplant patients. Ganciclovir may be more potent
      than acyclovir.

PMID- 16303003
TI  - Effect of anti-CD 20 antibody rituximab in patients with post-transplant
      lymphoproliferative disorder (PTLD).
AB  - Post-transplant lymphoproliferative disorders (PTLD) are a life-threatening
      complication following solid organ transplantation. Treatment with rituximab, a
      humanized anti-CD20 monoclonal antibody, has proved to be a promising approach
      and shown a low toxicity profile. Between February 1999 and April 2002, we
      conducted a multicentre phase II trial investigating rituximab as single agent in
      17 patients with PTLD. Transplanted organs were heart (n = 5), kidney (n = 4),
      lung (n = 4) and liver (n = 4). Patients were treated with four weekly doses of
      375 mg/m(2) of rituximab. The mean follow-up time is 24.2 months. Histology was
      distributed in 10 diffuse large cell-, 2 marginal zone-, 1 Burkitt-like lymphoma,
      1 Hodgkin-like PTLD and 3 polymorphic lymphoproliferations. Therapy was well
      tolerated and no severe adverse events were observed. The mean overall survival
      period is 37.0 months with 11 patients still living. In total, 9 patients (52.9%)
      achieved a complete remission, with a mean duration of 17.8 months. Partial
      remission was observed in 1 patient, minor remission in 2 patients, no change in
      3 patients and 1 patient experienced progressive disease. Two patients relapsed,
      at intervals 3 and 5 months after obtaining complete remission. Rituximab proved
      to be well tolerated and effective in the treatment of PTLD.

PMID- 16303005
TI  - HBsAg seropositive status and survival after renal transplantation: meta-analysis
      of observational studies.
AB  - The natural history of hepatitis B virus (HBV) infection after renal
      transplantation (RT) remains unclear. We conducted a systematic review of the
      published medical literature on the impact of HBV surface antigen (HBsAg)
      seropositivity on survival of RT recipients. We used the random effects model of
      DerSimonian and Laird to generate a summary estimate of the relative risk for
      mortality and graft loss in HBsAg positive RT recipients across the published
      studies. We identified six observational studies (6050 unique patients); all of
      them being cohort, retrospective studies. Pooling of study results demonstrated
      that HBsAg in serum was an independent and significant risk factor for death
      after RT; the summary estimate for relative risk was 2.49 with a 95% confidence
      interval (95% CI) of 1.64-3.78. A test for homogeneity of the relative risk
      across the studies gave a p-value of <0.0001. HBsAg seropositivity was an
      independent and significant risk factor for graft failure after RT; the summary
      estimate was 1.44 with a 95% CI of 1.02-2.04 (homogeneity test, p <0.0001). This
      meta-analysis shows that HBsAg positive RT recipients have an increased risk for
      mortality and graft failure compared to seronegative patients.

PMID- 16303004
TI  - Preemptive plasmapheresis and recurrence of FSGS in high-risk renal transplant
      recipients.
AB  - Recurrent focal segmental glomerulosclerosis (FSGS) following transplantation is
      ascribed to the presence of a circulating FSGS permeability factor (FSPF).
      Plasmapheresis (PP) can induce remission of proteinuria in recurrent FSGS. This
      study addressed the efficacy of pre-transplant PP in decreasing the incidence of
      recurrence in high-risk patients. Ten patients at high-risk for FSGS recurrence
      because of rapid progression to renal failure (n = 4) or prior transplant
      recurrence of FSGS (n = 6) underwent a course of 8 PP treatments in the peri
      operative period. Recurrences were identified by proteinuria >3 g/day and
      confirmed by biopsy. Seven patients, including all 4 with first grafts and 3 of 6
      with prior recurrence, were free of recurrence at follow-up (238-1258 days).
      Final serum creatinine in 8 patients with functioning kidneys averaged 1.53
      mg/dL. FSGS recurred within 3 months in 3 patients, each of whom had lost prior
      transplants to recurrent FSGS. Two of these progressed to end-stage renal disease
      (ESRD) and the third has significant renal dysfunction. Based on inclusion
      criteria, recurrence rates of 60% were expected if no treatment was given.
      Therefore, PP may decrease the incidence of recurrent FSGS in high-risk patients.
      Definitive conclusions regarding optimal management can only be drawn from
      larger, randomized, controlled studies.

PMID- 16303006
TI  - One-year post-transplant weight gain is a risk factor for graft loss.
AB  - Metabolic syndrome (MS) and obesity participate in the pathogenesis of kidney
      disease. We explored the impact of MS and post-transplant weight gain on graft
      survival. Two hundred ninety-two renal transplant recipients (RTRs) were included
      in the study. Various parameters (e.g. anthropometric, biological) were measured
      at the time of transplantation as well as 1 year post-transplant. The proportion
      of patients with overweight or obesity significantly increased during the first
      year post-transplant (p = 0.04). Mean weight gain was 2.7 +/- 5.8 kg. Thirty
      patients (10.3%) lost their graft during follow-up. In multivariate analysis,
      patients with an increase in body mass index (BMI) of more than 5% at 1 year post
      transplant had an increased risk of graft loss with (HR: 2.82 [95% CI: 1.11
      7.44], p = 0.015) or without death censoring (HR: 2.31 [95% CI: 1.06-5.04], p =
      0.035). Low creatinine clearance (HR: 4.72 [95% CI: 1.63-13.69], p = 0.004), high
      urinary protein excretion (HR: 3.21 [95% CI: 1.27-8.18], p = 0.014) and delayed
      graft function (DGF) (HR: 2.621 [95% CI: 1.07-6.39], p = 0.036) were also
      independent risk factors for graft loss. MS did not independently predict graft
      loss, partly due to significant interactions with low-grade inflammation. We
      conclude that post-transplant weight gain significantly reduces graft survival.

PMID- 16303007
TI  - Long-term cardiac outcomes in renal transplant recipients receiving fluvastatin:
      the ALERT extension study.
AB  - Renal transplant recipients (RTR) have an increased risk of premature
      cardiovascular disease. The ALERT study is the first trial to evaluate the effect
      of statin therapy on cardiac outcomes following renal transplantation. Patients
      initially randomized to fluvastatin or placebo in the 5-6 year ALERT study were
      offered open-label fluvastatin XL 80 mg/day in a 2-year extension to the original
      study. The primary endpoint was time to first major adverse cardiac event (MACE).
      Of 1787 patients who completed ALERT, 1652 (92%) were followed in the extension.
      Mean total follow-up was 6.7 years. Mean LDL-cholesterol was 98 mg/dL (2.5
      mmol/L) at last follow-up compared to a pre-study level of 159 mg/dL (4.1
      mmol/L). Patients randomized to fluvastatin had a reduced risk of MACE (hazards
      ratio [HR] 0.79, 95% CI 0.63-0.99, p = 0.036), and a 29% reduction in cardiac
      death or definite non-fatal MI (HR 0.71, 95% CI 0.55-0.93, p = 0.014). Total
      mortality and graft loss did not differ significantly between groups. Fluvastatin
      produces a safe and effective reduction in LDL-cholesterol associated with
      reduced risk of MACE in RTR. The lipid-lowering and cardiovascular benefits of
      fluvastatin are comparable to those of statins in other patient groups, and
      support use of fluvastatin in RTR.

PMID- 16303008
TI  - Influence of co-medication with sirolimus or cyclosporine on mycophenolic acid
      pharmacokinetics in kidney transplantation.
AB  - The pharmacokinetics of mycophenolic acid (MPA)--the active metabolite of
      mycophenolate mofetil (MMF)--is significantly influenced by co-medications. The
      impact of sirolimus on daily MPA exposure, however, has not been investigated so
      far. As a part of the study aimed at investigating the efficacy of Campath-1H
      induction therapy in a steroid-free regimen in kidney transplantation, MPA plasma
      levels were serially measured in 21 patients treated with low-dose sirolimus
      (SRL) or low-dose CsA both in addition to low-dose MMF over 12 months post
      operatively. Full pharmacokinetic profiles were compared at month 6 and 12 post
      surgery. Mean dose-adjusted MPA trough levels were 4.4-fold higher in patients on
      combined SRL and MMF than in those given CsA and MMF. Pharmacokinetic studies
      demonstrated that mean MPA C(max) and T(max) were comparable in the two groups,
      while mean MPA AUC(0-12) was higher in SRL than CsA treated patients. The
      pharmacokinetic profile of SRL- but not of CsA-group showed a second peak
      consistent with the enterohepatic recirculation of MPA. These findings suggest
      that SRL and CsA have different effects on MPA metabolism and/or excretion
      eventually affecting its immunosuppressive property and/or toxicity. CsA, but not
      SRL, inhibits MPA enterohepatic recirculation, reducing MPA daily exposure.

PMID- 16303009
TI  - Dendritic cell deficiency in the blood of kidney transplant patients on long-term
      immunosuppression: results of a prospective matched-cohort study.
AB  - Evidence from in vitro studies suggests that immunosuppressive drugs interfere
      with key functions of dendritic cells (DCs), but the in vivo relevance of these
      findings is elusive. We prospectively analyzed the major DC precursor subsets in
      the blood of kidney transplant recipients on long-term immunosuppression (> or =1
      year). A total of 87 patients were compared to 87 age- and sex-matched controls.
      Total DC numbers and the precursor subsets, myeloid type 1 DCs, myeloid type 2
      DCs (mDC1, mDC2) and plasmacytoid DCs (pDCs) were identified by four color flow
      cytometry. Long-term immunosuppression was associated with significant reduction
      of all major DC subsets in comparison to healthy controls (mDC1 p < 0.001; mDC2 p
      < 0.0001; two-tailed Mann-Whitney U-test) with the strongest negative impact on
      pDCs (p < 0.00001). In contrast, total leukocyte numbers were not significantly
      affected. Analysis of the relative impact of different agents revealed a
      significant impact of prednisolone on pDCs (p = 0.009) and mDCs2 (p = 0.006). The
      functional relevance of pDC deficiency was confirmed independently by Interferon
      alpha analysis after Toll-like receptor 7 (p < or = 0.001) and 9 (p < 0.05)
      stimulation. These results indicate for the first time a profound negative impact
      of long-term immunosuppression on major DC subsets in kidney transplant
      recipients. DC deficiency may have important implications with respect to viral
      infections and tumor development.

PMID- 16303010
TI  - Prospective registry-based observational cohort study of the long-term risk of
      malignancies in renal transplant patients treated with mycophenolate mofetil.
AB  - This large prospectively conducted observational cohort study examined the risk
      of lymphoma and other malignancies with mycophenolate mofetil (MMF) in de novo
      renal transplant recipients. A total of 6751 patients receiving MMF, and an equal
      number of matched controls receiving non-MMF-based immunosuppression, were
      identified from two large registries (Organ Procurement and Transplantation
      Network/United Network for Organ Sharing (OPTN/UNOS) and Collaborative Transplant
      Study (CTS)) and followed for 3 years. The primary endpoint was development of
      lymphoma. Secondary endpoints included development of any malignancy. There was
      no evidence of any increased risk of developing lymphoma or malignancy with MMF.
      The risk of developing lymphoma with MMF compared with the non-MMF cohort was not
      higher in either the CTS registry (relative risk (95% confidence interval); 0.4
      (0.17-0.94)) or the OPTN/UNOS registry (1.04 (0.61-1.78)). In the MMF group,
      there was a trend toward a lower risk of malignancy in both registries (OPTN/UNOS
      0.86 (0.69-1.07); CTS 0.79 (0.61-1.02)) and a significant increase in time to
      malignancy in the CTS dataset (p < 0.026). This study has demonstrated that MMF
      is not associated with an increased risk of lymphoma or other malignancies post
      renal transplant, and may even be associated with a lower risk in some
      populations.

PMID- 16303011
TI  - Addition of MMF to dual immunosuppression does not increase the risk of malignant
      short-term death after liver transplantation.
AB  - Immunosuppression is often incriminated for the increased risk of post-transplant
      malignancies. To examine whether triple- (MMF+Tacro+CS) versus dual-drug therapy
      (Tacro+CS) is associated with an increased incidence of malignancy, or death due
      to malignancy, data from a large registry of liver transplant recipients were
      analyzed. Data from adult primary liver recipients reported to the Scientific
      Registry of Transplant Recipients between June 1, 1995, and April 30, 2004, and
      recorded at transplant on triple-drug (n = 9180) or dual-drug (n = 10 099)
      therapy were included. Kaplan-Meier survival analysis showed no significant
      differences in death due to malignancy 4 years post-transplantation between the
      treatment groups. Multivariable analysis using Cox proportional hazard models
      confirmed no differences in risk of death due to malignancy between the groups
      (HR: 0.83, p = 0.107). Incidence of any post-transplant malignancy was also not
      significantly different. Older recipient age and cause of liver disease were
      significantly associated with an increased risk of malignancy-related death.
      These data utilizing relatively short follow-up suggest the addition of MMF to
      Tacro+CS at transplant is not associated with death due to malignancy, at least
      in the short term. Individual recipient factors appear to be important risk
      factors for malignancy-related death; elucidating these risk factors can assist
      in identifying who should be monitored most aggressively for post-transplant
      malignancies.

PMID- 16303012
TI  - Acute graft versus host disease after liver transplantation: patterns of
      lymphocyte chimerism.
AB  - The diagnosis of acute graft versus host disease (aGVHD) following liver
      transplantation can be difficult, since many of the clinical signs can be caused
      by drug reactions or viral infections. To establish criteria for the persistence
      of donor T-cells versus engraftment, we measured donor T-cells by short tandem
      repeat (STR) assays in 49 liver transplant patients for 8 or more weeks post
      transplant. Donor CD3+ T-cells were detected in 38 of 49 patients, on POD 2 with
      a mean level of 5%. The top of the 99% confidence interval for weeks 1, 2, 3, 4
      and 8 were 11, 6, 3, 2 and 3%. Donor CD8+ T-cells were measured in eight
      patients. The level of CD8+ T-cells was much less than that for CD3+ T-cells,
      except in two cases of apparent aGVHD. One patient developed severe aGVHD with
      donor T-cells as high as 84%. The other had 10% donor T-cells for more than 16
      weeks associated with fever and neutropenia. We tested the sensitivity of PCR-ssp
      typing of HLA DR/DQ for donor T-cells. At least one donor type was detected in
      all samples with 1% or more donor DNA. Thus, higher levels of donor T-cell
      chimerism, particularly with a high proportion of CD8+ T-cells, strongly supports
      a diagnosis of aGVHD.

PMID- 16303013
TI  - Select utilization of obese donors in living donor liver transplantation:
      implications for the donor pool.
AB  - Living donor liver transplantation evolved in response to donor shortage. Current
      guidelines recommend potential living donors (LD) have a body mass index (BMI)
      <30. With the current obesity epidemic, locating nonobese LD is difficult. From
      September 1999 to August 2003, 68 LD with normal liver function test (LFTs) and
      without significant comorbidities underwent donor hepatectomy at our center. Post
      operative complications were collected, including wound infection, pneumonia,
      hernia, fever, ileus, biliary leak, biliary stricture, thrombosis, bleeding,
      hepatic dysfunction, thrombocytopenia, deep venous thrombosis, pulmonary
      embolism, difficult to control pain, depression and anxiety. Complication rates
      for LD with BMI >30 (n = 16) and BMI <30 (n = 52) were compared. The incidence of
      wound infection increased with BMI, 4% for nonobese and 25% for obese LD (p =
      0.024). There were no statistically significant differences for all other
      complications. No LD died. Recipient survival was 100% with obese LD and 80% with
      nonobese LD (p = 0.1). Select donors with a BMI >30 may undergo donor hepatectomy
      with acceptable morbidity and excellent recipient results. Updating current
      guidelines to include select LD with BMI >30 has the potential to safely increase
      the donor pool.

PMID- 16303014
TI  - Human herpesvirus 6 in bronchalveolar lavage fluid after lung transplantation: a
      risk factor for bronchiolitis obliterans syndrome?
AB  - Bronchiolitis obliterans syndrome (BOS) is the limiting factor to long-term
      survival after lung transplantation. Previous studies suggested respiratory viral
      tract infections are associated with the development of BOS. To identify the
      impact of virus detection in bronchoalveolar lavage (BAL) fluid, we analyzed BAL
      samples from 87 consecutive lung transplant recipients for human herpesvirus
      (HHV)-6, Epstein-Barr virus, Herpes simplex virus 1/2, Cytomegalovirus,
      respiratory syncytical virus and adenovirus by PCR. Acute rejection, BOS and
      death were recorded for a mean follow-up time of 3.27 +/- 0.47 years. Results of
      PCR analysis and other potential risk factors were entered into a Cox regression
      analysis of BOS predictors and death. Only acute rejection was a distinct risk
      factor for BOS of all stages, death and death from BOS. HHV-6 was detected in 20
      patients. Univariate and multivariate analysis revealed that HHV-6 was associated
      with an increased risk to develop BOS > orb = stage 1 and death, separate from
      the risk attributable to acute rejection. Identification of HHV-6 DNA in BAL
      fluid is a potential risk factor for BOS. Our results warrant further studies to
      elucidate a possible causal link between HHV-6 and BOS.

PMID- 16303015
TI  - Prevention of bleeding after islet transplantation: lessons learned from a
      multivariate analysis of 132 cases at a single institution.
AB  - Islet transplantation is being offered increasingly for selected patients with
      unstable type 1 diabetes. Percutaneous transhepatic portal access avoids a need
      for surgery, but is associated with potential risk of bleeding. Between 1999 and
      2005, we performed 132 percutaneous transhepatic islet transplants in 67
      patients. We encountered bleeding in 18/132 cases (13.6%). In univariate
      analysis, the risk of bleeding in the absence of effective track ablation was
      associated with an increasing number of procedures (2nd and 3rd procedures with
      an odds ratio (OR) of 9.5 and 20.9, respectively), platelets count <150,000 (OR
      4.4), elevated portal pressure (OR 1.1 per mm Hg rise), heparin dose > or =45
      U/kg (OR 9.8) and pre-transplant aspirin (81 mg per day) (OR 2.6, p = 0.05). A
      multivariate analysis further confirmed the cumulative transplant procedure
      number (p < 0.001) and heparin dose > or =45 U/kg (p = 0.02) as independent risk
      factors for bleeding. Effective mechanical sealing of the intrahepatic portal
      catheter tract with thrombostatic coils and tissue fibrin glue completely
      prevented bleeding in all subsequent procedures (n = 26, p = 0.02). We conclude
      that bleeding after percutaneous islet implantation is an avoidable complication
      provided the intraparenchymal liver tract is sealed effectively.

PMID- 16303016
TI  - Do incentives matter? Providing benefits to families of organ donors.
AB  - Whether the number of organs available for transplant would be positively or
      negatively affected by providing benefits to families of organ donors has been
      debated by policymakers, ethicists and the transplant community at large. We
      designed a telephone survey to measure public opinion regarding the use of
      benefits in general and of five types in particular: funeral benefits, charitable
      contributions, travel/lodging expenses, direct payments and medical expenses. Of
      the 971 adults who completed the survey (response rate = 69%), all were from
      Pennsylvania households, 45.6% were registered organ donors, and 51.7% were
      nonwhite. Although 59% of respondents favored the general idea of incentives,
      support for specific incentives ranged from 53% (direct payment) to 84% (medical
      expenses). Among those registered as donors, more nonwhites than whites supported
      funeral benefits (88% vs. 81%; p = 0.038), direct payment (63% vs. 41%; p <
      0.001) and medical expenses (92% vs. 84%; p = 0.013). Among those not registered
      as donors, more nonwhites supported direct payment (64% vs. 46%; p = 0.001). Most
      respondents believed that benefits would not influence their own behavior
      concerning donation but would influence the behavior of others. While benefits
      appear to be favored, their true impact can only be assessed through pilot
      programs.

PMID- 16303017
TI  - Alemtuzumab induction and sirolimus plus mycophenolate mofetil maintenance for
      CNI and steroid-free kidney transplant immunosuppression.
AB  - We performed a pilot study in which 22 kidney recipients (14 LD: 8 DCD) were
      given alemtuzumab induction (30 mg day 0 and 1), steroids (500 mg mp day 0 and 1,
      none thereafter), mycophenolate mofetil (MMF) maintenance (500 mg b.i.d) and
      sirolimus (concentration controlled 8-12 ng/mL). With a mean follow-up of 15.9
      months, patient survival is (21/22) 96% and graft survival (19/22) 87%. Acute
      rejections occurred in (8) 36.3% (two humoral). Of 19 surviving grafts, 18 (95%)
      remain steroid and 15 (79%) CNI-free. At 1 year, mean creatinine was 1.43 mg/dL.
      Overall infection rates were low, but 2 patients developed severe acute
      respiratory distress syndrome (ARDS) at month 3 and 7, respectively, resulting in
      mortality in one and a graft loss in the other. No cancer or PTLD was observed.
      Leukopenia was common and MMF dose was reduced or eliminated in 6/22 (27%)
      patients. The reported higher than expected rate of acute rejection, leukopenia
      and possible pulmonary toxicity suggests excessive morbidity. Modifications such
      as an initial period of CNI use should be considered.

PMID- 16303018
TI  - Renal cell carcinoma in kidney allografts: a case series from a single center.
AB  - In kidney transplant recipients, renal cell carcinoma (RCC) occurs either in the
      native kidney or, less frequently, in the grafted kidney. Here, we report a
      series of rare cases involving 5 patients from a single center who developed RCC
      in their grafts. The diagnosis was made serendipitously by ultrasound. The time
      lapse post-transplant varied from 4 to 17 years. Surgical treatment consisted of
      nephron-sparing surgery (NSS) in four cases and a secondary radical nephrectomy
      in one case. All tumors were less than 4 cm in diameter. The histopathology was
      clear cell type in four cases and papillary RCC in one case. Patients treated by
      NSS retained kidney function for 2 years or more, and none of them presented
      early neoplasia recurrence. In conclusion, NSS can be performed safely in grafted
      kidneys to treat incidental RCC. It prevents an immediate return to dialysis for
      patients.

PMID- 16303019
TI  - Is administration of rituximab at 375 mg/m without splenectomy appropriate for
      ABO-incompatible renal transplant?

PMID- 16303021
TI  - Chimerism after solid organ transplantation.

PMID- 16303023
TI  - Calcineurin inhibitor withdrawal from sirolimus-based therapy in kidney
      transplantation: a systematic review of randomized trials.

PMID- 16303025
TI  - Pleistophora infestation in fathead minnows, Pimephales promelas (Rafinesque).
AB  - Pleistophora infestation was observed in adult fathead minnows, Pimephales
      promelas, held under laboratory conditions. Fish were clinically healthy, and
      presented no gross findings at necropsy. Histopathology revealed parasitic stages
      only in the ovaries. Spores within sporophorous vesicles were mainly encountered
      in late vitellogenic oocytes and were ultrastructurally identified as a
      microsporidian parasite. Heavily parasitized oocytes underwent degeneration
      followed by the release of spores into the ovarian interstitium. Degenerating
      oocytes and interstitial spores caused ovarian inflammation. Male fish showed no
      parasites in the testes. Parasitic infestation was compared with body length,
      body weight, gonadal weight, gonadosomatic index and plasma vitellogenin levels,
      and revealed no statistically significant differences between non-parasitized and
      parasitized females. The isolated holding conditions of the fish and the presence
      of parasitic stages in the ovaries suggested that an infestation with
      Pleistophora ovariaeSummerfelt, 1964 was more probable than that with
      Pleistophora mirandellae (Vaney & Conte, 1901).

PMID- 16303026
TI  - Mortality patterns in infectious salmon anaemia virus outbreaks in New Brunswick,
      Canada.
AB  - Mortality levels attributed to infectious salmon anaemia viral (ISAV) infections
      were examined at the net pen and site level in the 1996 smolt year class in three
      areas of New Brunswick, Canada. The year class in this region was the first known
      to have potential exposure to ISAV beginning at the time of seawater transfer.
      There was considerable variability in mortality patterns among net pen groups of
      fish. Net pen outbreak definitions were based on at least seven high mortality
      days in which there were at least 100 per 100 000 fish per day or >5% cumulative
      mortality for the study period. There were 106 net pen outbreaks in a study
      population consisting of 218 net pens. Although the number of new cases decreased
      as water temperature decreased, overall mortality levels at the study sites did
      not decrease noticeably. The median peak daily mortality rate during outbreaks
      was 492 per 100 000 fish per day, with 10% of cases experiencing >5200
      mortalities per 100 000 fish per day. The median duration of outbreaks in net
      pens for which the fish were not slaughtered during the outbreak was 33 days and
      the median total loss in those outbreaks was 6600 per 100 000 fish.

PMID- 16303027
TI  - Risk factors associated with mortalities attributed to infectious salmon anaemia
      virus in New Brunswick, Canada.
AB  - Outbreaks of unexplained mortalities attributed to infectious salmon anaemia
      (ISA) were examined in the 1996 year class of Atlantic salmon in three regions of
      New Brunswick, Canada. A total of 218 net pens at 14 sites deemed to have been
      exposed to ISA virus (ISAV) were surveyed for mortality records and management,
      environmental and host characteristics. Based on definitions of mortality
      patterns, clinical ISA disease outbreaks occurred in 106 net pens. There were
      eight sites in which >50% of net pens experienced ISA outbreaks during the study
      period. Factors related to their potential role in transmission of virus to new
      sites or new net pens at the same site were identified as sea lice vectors,
      divers visiting multiple sites, sites belonging to companies with more than one
      site, exposure to other year classes at the site, and proximity to other infected
      net pens. Host resistance factors associated with greater risk of outbreaks were
      identified as larger groupings, general health following smolt transfer,
      stressful husbandry procedures during growout, and health or productivity during
      colder water periods. Despite very close proximity between sites, modification of
      these management factors would probably influence the severity of mortalities
      caused by ISAV.

PMID- 16303028
TI  - Spatio-temporal variation in serum chemistry of the lobster, Homarus americanus
      Milne-Edwards.
AB  - Monthly variations in serum chemistry of the American lobster, Homarus americanus
      Milne-Edwards, were investigated at one location in Long Island Sound (LIS).
      Comparisons between three locations within and outside LIS were also made for a
      single time point. Most serum analytes displayed significant fluctuation over the
      study period and between locations. Temporal patterns could be classified as: low
      in cool months/high in warm months, i.e. Na, Cl, Na:K ratio, Ca, albumin:globulin
      ratio, percentage Fe saturation; high in cool months/low in warm months, i.e. pH,
      K, urea, total protein, albumin, globulin, alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), lipaemia; June spike, i.e. glucose,
      cholesterol, creatine kinase, iron, transferrin iron-binding capacity; other less
      obvious fluctuations, i.e. Mg, PO4; and no apparent fluctuation, i.e. HCO3,
      alkaline phosphatase. The proportion of samples correctly classified into month
      of collection by a subset of 13 analytes using discriminant analysis improved as
      the months progressed from May (0.75) to October (>0.95). Discriminant analysis
      also resolved 96.5% of samples by location. The significant depression of serum
      calcium at the eastern LIS site correlates with excretory calcinosis, a calcium
      storage disease described from lobsters at this site, but contrasts with a
      seasonal elevation in serum calcium recorded in the temporal component of the
      study. Serum proteins, the electrolytes Ca and K and the enzymes ALT and AST
      proved to have the strongest spatio-temporal patterns of variation. Serum
      chemistry is a useful research tool for lobster populations, but the dearth of
      information on the homology of analyte functions in this species with those in
      vertebrate species makes interpretation of the results challenging. Late
      summer/autumn water conditions appear to cause stress for lobsters in LIS.

PMID- 16303029
TI  - Influence of dietary lipid composition on cardiac pathology in farmed Atlantic
      salmon, Salmo salar L.
AB  - The present study investigated the short-term (5 months) effect of replacing
      dietary marine oils with vegetable oils on the development of arteriosclerotic
      changes in the heart of Atlantic salmon, Salmo salar. The experiment was
      performed as a randomized observer-blinded and controlled trial. Farmed Atlantic
      salmon were randomly sampled from a study population containing 900 individuals.
      The salmon were divided into three groups and given diets with either 100% fish
      oil (Diet 1), a 50/50% mixture of fish oil and rapeseed oil (Diet 2) or 100%
      rapeseed oil (Diet 3). Ten sexually immature salmon from each dietary group were
      sampled in March and August 2002. Additionally, 47 sexually mature wild salmon
      were randomly collected in mid-September 2001. Serial histological sections were
      taken from the bulbus arteriosus and ventricle wall for histopathological
      evaluation of the coronary arteries and myocardium. No significant differences in
      mean coronary changes recorded by the main variable 'mean range lesion' (MRL)
      were detected between the groups in March or August. MRL increased significantly
      between March and August with Diet 2 (P < 0.01), was nearly significant with Diet
      3 (P = 0.06) and was unchanged with Diet 1. This pattern coincided with the Diet
      2 group having the highest increase in heart weight. MHC class II immunoreactive
      cells in the coronary changes were detected in sections from one individual in
      each group. Heart weight was the most dominant variable in the data set and
      explained linearly 15.5% of the variation in MRL. Body weight, fish length and
      heart weight were all significantly, positively and linearly correlated to MRL.
      The Diet 2 group had the highest growth rate and also exhibited a significant
      increase in MRL. The possible influence of diet composition on weight gain and
      MRL needs to be further elucidated. Increase in heart weight seems to be the
      dominating predictor of the appearance of MRL in Atlantic salmon. However, the
      present results cannot exclude the possibility that differences in fatty acid
      composition of fish feed can influence the development of arteriosclerotic
      changes in Atlantic salmon.

PMID- 16303030
TI  - Clinical implications of immediate-release PPI therapy in the management of GERD
      and upper GI bleeding. Introduction.

PMID- 16303031
TI  - Review article: oesophageal pH monitoring--technologies, interpretation and
      correlation with clinical outcomes.
AB  - Using a simple 'test' to diagnose gastro-oesophageal reflux disease is difficult
      because accurately measuring gastric refluxate and correlating reflux events with
      symptom episodes is complex. This paper reviews the safety, tolerability and
      diagnostic accuracy of Bravo (Medtronic, Shoreview, MN, USA), ambulatory
      oesophageal pH monitoring technology. Catheter-based pH electrodes inhibit
      patients' normal activity, and can yield erroneous results because of placement
      or subsequent migration of the probe or errors in the thermal compensation
      algorithm that is requisite for antimony pH electrodes. Bravo pH studies reliably
      discriminated oesophagitis patients from controls, but are less discriminatory in
      endoscopy-negative gastro-oesophageal reflux disease patients. The Bravo system
      can be accurately placed using endoscopic landmarks and pH studies demonstrated
      more accurate in vivo pH recording than with a catheter-based system. The Bravo
      system detected fewer reflux events of short duration compared with a catheter
      based system. Studies examining the correlation between reflux events and
      symptoms have not yet been conducted using the Bravo system. In conclusion, the
      Bravo system offers a more user-friendly ambulatory pH monitoring technique that
      more accurately records pH compared with a catheter-based system. More research
      is needed to determine whether the detection of reflux events with Bravo will
      provide a good correlation with symptom episodes.

PMID- 16303032
TI  - Review article: the unmet needs in delayed-release proton-pump inhibitor therapy
      in 2005.
AB  - Proton-pump inhibitors have been highly effective in managing acid-related
      gastrointestinal disorders, but challenges remain. This paper reviews the
      challenges in the management of patients with gastro-oesophageal symptoms who do
      not respond adequately to proton-pump inhibitor therapy; the treatment of
      patients with non-variceal upper gastrointestinal bleeding; the prevention of
      stress-related mucosal bleeding; the treatment and prevention of non-steroidal
      anti-inflammatory drug-related gastrointestinal injury; and the optimal
      combination of antisecretory and antibiotic therapy for the eradication of
      Helicobacter pylori infection, all of which represent unmet clinical needs.
      Antisecretory therapy with a rapid onset of action and sustained antisecretory
      effect may help to address some of the unmet needs discussed, especially in the
      management of gastro-oesophageal reflux disease, non-variceal upper
      gastrointestinal bleeding and non-steroidal anti-inflammatory drug-related
      gastrointestinal complications.

PMID- 16303033
TI  - Review article: similarities and differences among delayed-release proton-pump
      inhibitor formulations.
AB  - Proton-pump inhibitors are acid-labile, and require an enteric coating to protect
      them from degradation in the stomach when given orally. However, this leads to
      delayed absorption and onset of action of the proton-pump inhibitor. This article
      aims to review the similarities and differences between the various formulations
      of delayed release proton-pump inhibitors. Delayed-release omeprazole and delayed
      release lansoprazole have been suspended in sodium bicarbonate for tube
      administration; however, for omeprazole, absorption is further impaired and
      antisecretory effects are disappointing. Although such formulations may be more
      convenient for clinical use in certain patient groups, absorption of the proton
      pump inhibitor is still influenced by residual enteric coating. There are few
      differences among the currently available delayed-release proton-pump inhibitors
      with respect to their pharmacodynamic effects during chronic administration.
      There are minor formulation-based pharmacokinetic differences among these agents,
      primarily reflected in their bioavailability following the first few doses.
      Differences in bioavailability may explain slight differences in the rate of
      onset of maximal antisecretory effect. However, minor pharmacodynamic and
      pharmacokinetic differences are not associated with meaningful differences in
      clinical outcomes.

PMID- 16303034
TI  - Review article: immediate-release proton-pump inhibitor therapy--potential
      advantages.
AB  - The absorption of most oral proton-pump inhibitors is delayed by the enteric
      coating required to protect the acid-labile proton-pump inhibitor from
      degradation in the stomach and, as a result, antisecretory effect is also
      delayed. This article provides an overview of the pharmacokinetics and
      pharmacodynamics of a new immediate-release omeprazole [(IR-OME) Zegerid power
      for oral suspension; Santarus Inc., San Diego, CA, USA] and its potential
      advantages over delayed-release proton-pump inhibitors. Immediate-release
      omeprazole has a higher mean peak plasma omeprazole concentration (C(max)) and a
      significantly shorter mean time to reach C(max) (t(max)) than delayed-release
      omeprazole. Immediate-release omeprazole 40 mg has a prolonged antisecretory
      effect with median intragastric pH above 4.0 for 18.6 h/day at steady-state,
      after 7 days of once daily dosing. The sodium bicarbonate in immediate-release
      omeprazole protects the uncoated omeprazole from degradation by gastric acid. The
      accelerated antisecretory action of immediate-release omeprazole compared with
      delayed-release omeprazole may be due to the activation of proton pumps by the
      rapid neutralization of intragastric acid by the sodium bicarbonate. The faster
      onset of action seen with immediate-release omeprazole is not achieved by using
      an antacid with a delayed-release proton-pump inhibitor, because administering
      antacids with conventional delayed-release proton-pump inhibitors does not
      significantly enhance absorption of the proton-pump inhibitor. In conclusion,
      immediate-release omeprazole is associated with rapid absorption of omeprazole
      and rapid onset of antisecretory effect, without compromising the duration of
      acid suppression.

PMID- 16303035
TI  - Review article: putting immediate-release proton-pump inhibitors into clinical
      practice--improving nocturnal acid control and avoiding the possible
      complications of excessive acid exposure.
AB  - Nocturnal gastro-oesphageal reflux is an under-appreciated clinical challenge.
      This condition may cause symptoms such as nocturnal heartburn, or it may be
      asymptomatic. In addition, patients may experience sleep disturbances that can
      potentially lead to complications such as erosive oesophagitis and Barrett's
      oesophagus, and may be a risk factor for development of oesophageal
      adenocarcinoma. Delayed-release proton-pump inhibitors (PPIs) have traditionally
      been effective in treating both daytime and night-time reflux symptoms, but are
      limited in control of nocturnal acidity by their pharmacodynamic characteristics.
      This narrative review addresses the prevalence, impact and pharmacologic
      approaches used to control nocturnal acidity. Methods to optimize nocturnal acid
      control include careful attention to dosing schedule, using higher doses of PPIs,
      adding an histamine H2-receptor antagonist at bedtime to once or twice daily
      delayed-release PPI, or using immediate-release omeprazole (Zegerid powder for
      oral suspension; Santarus, Inc., San Diego, CA, USA). This new formulation
      appears to provide sustained control of intragastric pH at steady state, and when
      dosed at bedtime, and may be effective in improving control of nocturnal pH and
      treating night-time GERD.

PMID- 16303036
TI  - Review article: alternative approaches to the long-term management of GERD.
AB  - Although proton-pump inhibitors are highly effective for the treatment of gastro
      oesophageal reflux disease, there are issues with long-term maintenance therapy:
      not all patients require full daily dose for maintenance treatment, some patients
      are reluctant to take long-term daily medication, and long-term PPI therapy is
      inadequate for some patients. This article aims to review alternatives to daily
      proton-pump inhibitor therapy for the long-term management of gastro-oesophageal
      reflux disease, including intermittent or on-demand proton-pump inhibitor use, as
      well as endoscopic and surgical options. On-demand proton-pump inhibitor therapy
      has demonstrated efficacy in achieving acceptable symptom control, healing and
      maintenance of quality of life for a proportion of patients with gastro
      oesophageal reflux disease. Endoscopic antireflux procedures can reduce the need
      for proton-pump inhibitor therapy, but safety and durability of these procedures
      require more study. Surgical treatment of gastro-oesophageal reflux disease in
      properly selected patients has demonstrated efficacy in reducing symptoms and the
      need for proton-pump inhibitor therapy; however, long-term follow-up suggests
      that it is not a permanent solution for many patients. While daily proton-pump
      inhibitor therapy remains the main treatment regimen option for most patients
      with gastro-oesophageal reflux disease, on-demand therapy may prove effective for
      many patients. Endoscopic anti-reflux therapies and surgery are options for
      patients who prefer nonpharmacological treatment, but experience is limited at
      this point in time for the former.

PMID- 16303037
TI  - Review article: prevention of stress-related mucosal bleeding with proton-pump
      inhibitors.
AB  - Stress-related gastric mucosal bleeding occurs in a substantial number of
      critically ill patients, with clinically important gastrointestinal bleeding
      prolonging intensive care stay and increasing mortality. This paper reviews the
      role of proton-pump inhibitors in the prevention of stress-related mucosal
      bleeding. Bleeding prophylaxis appears to be warranted in patients in intensive
      care units on mechanical ventilation or those who have coagulopathy. Intravenous
      histamine H2 receptor antagonists, particularly cimetidine, have demonstrated
      efficacy for the prevention of bleeding in critically ill patients. Standard
      delayed-release proton-pump inhibitors have not been extensively studied in this
      patient group, but there are some data to support their efficacy in increasing
      intragastric pH, and in the case of intravenous pantoprazole in preventing
      gastrointestinal bleeding. In a large, randomized controlled trial, immediate
      release omeprazole [(IR-OME) Zegerid powder for oral suspension; Santarus Inc.,
      San Diego, CA, USA] administered via gastric tube, was as effective as
      intravenous cimetidine in the prevention of clinically significant bleeding, and
      more effective in increasing gastric pH. Effective antisecretory therapy does not
      appear to increase the risk of nosocomial pneumonia. In conclusion, immediate
      release omeprazole provides a safe and effective alternative to intravenous
      cimetidine for the prevention of stress-related mucosal bleeding in critically
      ill patients.

PMID- 16303038
TI  - Review article: the role of antisecretory therapy in the management of non
      variceal upper gastrointestinal bleeding.
AB  - Non-variceal, upper gastrointestinal bleeding accounts for 300,000
      hospitalizations annually in the US and the risk of rebleeding and mortality
      remain high. The aim of this study was to review the incidence and causes of non
      variceal upper gastrointestinal haemorrhage, criteria for early discharge, risk
      stratification and intravenous vs. oral proton-pump inhibitor use. Peptic ulcer
      disease accounts for 45% of all admissions for upper gastrointestinal bleeding.
      Clinical and endoscopic predictors of adverse outcome have been identified. The
      Rockall scoring system identifies patients who can be considered for early
      discharge after endoscopy. Evidence supports the use of intravenous proton-pump
      inhibitor therapy for patients with bleeding ulcers associated with high-risk
      stigmata. Patients who are clinically stable and in whom upper endoscopy has
      shown an ulcer with a clean base or a flat pigmented spot have a low risk for
      rebleeding and may be discharged early on oral proton-pump inhibitor therapy.
      Proton-pump inhibitor treatment reduces ulcer rebleeding but does not affect
      overall mortality. In the US, most patients with ulcer bleeding have low-risk
      stigmata, and thus, can be treated with oral proton-pump inhibitors and
      discharged early.

PMID- 16303039
TI  - Can the management of mild dyskaryosis be refined?

PMID- 16303040
TI  - Prevalence of high-grade CIN following mild dyskaryotic smears in different age
      groups.
AB  - OBJECTIVE: The new guidelines of the British Society of Colposcopy and Cervical
      Pathology suggest that women should be offered colposcopy after only one mildly
      dyskaryotic smear. This is expected to generate increased workload for the
      colposcopy clinics, at least in the short term. The main objective of this study
      was to estimate the incidence of high-grade cervical intraepithelial neoplasia
      (CIN) in women with mildly dyskaryotic smears and investigate whether there is
      any variation in different age groups. The rationale was to determine whether we
      could reduce the burden on colposcopy services by prioritizing the mild
      dyskaryotic referrals by age, as we hypothesized that high-grade CIN is less
      frequent in younger women. METHODS: The study sample included all women who were
      referred for colposcopy with a cervical smear suggesting mild dyskaryosis (with
      or without koilocytosis) from April 2000 to March 2003. RESULTS: We studied 510
      women. They were divided into three age groups (<20, 20-25 and >25 years). The
      overall prevalence of high-grade CIN (CIN II and III) was 28.7%. The positive
      predictive value of a mildly dyskaryotic smear for high-grade CIN was similar in
      all groups. CONCLUSIONS: Our results show that we are not in a position to
      prioritize our referrals by age group and reduce the initial pressure for
      colposcopies. We are also concerned that with the implementation of the new
      guidelines, a significant number of women <25 years will be carrying high-grade
      CIN for more than 5 years before they are first screened.

PMID- 16303041
TI  - Outcome of women with index smear showing mild dyskaryosis: effects of age and
      evidence of HPV infection.
AB  - OBJECTIVE: Recent national guidelines (NHSCSP Document 20) recommend colposcopy
      referral after one mildly dyskaryotic smear, compared with the current practice
      of cytological surveillance and referral if the abnormality persists. The aim of
      this study was to identify the percentage of women whose first abnormal smear,
      showing mild dyskaryosis, returned to normal with cytological surveillance.
      Colposcopy could therefore be avoided in this group. This study also assessed
      whether age or human papillomavirus (HPV) status affected this outcome and the
      impact of non-attenders on the reliability of surveillance. METHODS: This was a
      retrospective study examining the follow-up of 1484 women whose first abnormal
      smear showed mild dyskaryosis between 1996 and 1998. The possible outcomes were:
      persisting abnormality referred to colposcopy, follow-up by cytology alone
      (negative follow-up), lost to follow-up or moved out of the area. Results were
      further assessed in terms of age (over or under 35 years) and cytological
      evidence of HPV effect. RESULTS: In this study 50.9% of women, presenting with a
      mildly dyskaryotic smear, returned to normal without colposcopy within the follow
      up period of 6-8 years. Age (over/under 35) or cytological evidence of HPV did
      not significantly affect this figure. CONCLUSIONS: Immediate colposcopy would
      overtreat 50% of the study group resulting in 159 extra colposcopies in this unit
      per year. High-grade abnormalities were twice as prevalent (22% versus 11%) in
      the younger age group, suggesting that younger rather than older women would
      benefit from immediate referral.

PMID- 16303042
TI  - Cytological study of early cervical adenocarcinoma: special reference to the
      depth of invasion.
AB  - OBJECTIVE: Early cervical adenocarcinoma (ECA) with a tumour depth of <3 mm has a
      good prognosis. To clarify the cytological features of ECAs with depth <3 mm,
      these were compared with those of ECA with 3-5 mm and invasive adenocarcinoma
      (IA) invading the cervical wall with more than 5 mm in depth. METHODS: The
      cervical cytological features of ECAs with depth <3 mm (14 cases) were compared
      with those of ECA with 3-5 mm (four cases) and IA (13 cases). Cytologically, the
      presence or absence of tumour diathesis, number of atypical cells, crowded cell
      groups, groups with glandular structures, feathering, groups with palisading
      borders, rosettes, clusters, cell shape and size, nuclear shape and size,
      nucleolar shape and size, chromatin distribution, border and character of
      cytoplasm, and single cell pattern were evaluated. RESULTS: A tumour diathesis
      was seen in five of 14 ECA <3 mm in depth (36%), all four ECA with 3-5 mm (100%)
      and 11 of 13 IA with more than 5 mm (85%). Single cells, macronucleoli and
      coarsely granular chromatin pattern were less frequent in ECA of <3 mm than that
      in ECA with 3-5 mm and IA. The number of atypical cells and glandular structures
      in ECA was significantly less than that in IA. Cell crowding, feathering,
      palisading and rosettes were common in both ECA and IA. CONCLUSION: The
      characteristic cytological features of ECA with depth <3 mm, having a good
      prognosis, were clean background, fewer single cells and macronucleoli, and less
      frequent coarsely granular chromatin pattern compared with those in ECA with 3-5
      mm and IA. The number of atypical cells and glandular structures in ECA was
      significantly less than that in IA. Familiarity with the cytological features of
      ECA and its mimics is essential.

PMID- 16303043
TI  - Atypical glandular cells: criteria to discriminate benign from neoplastic lesions
      and squamous from glandular neoplasia.
AB  - OBJECTIVE: To evaluate the presence of some criteria in cervical smears with
      atypical glandular cells and their correlation with histological patterns to
      identify pre-neoplastic and neoplastic lesions. METHODS: Seventy-three women
      referred with an atypical glandular cell smear, who had undergone conization or
      hysterectomy, were included in this study. Referral Pap smears were reviewed
      using the set of 27 cyto-morphological criteria that was correlated with the
      histological diagnosis. RESULTS: Histological results showed intraepithelial or
      invasive neoplasia in 35 (48%) cases and benign lesions in 38 (52%) cases. After
      logistic regression and decision tree analysis an increased nuclear/cytoplasmic
      ratio and the presence of dyskeratotic cells were strongly associated with
      intraepithelial or invasive neoplasia and the differential cyto-morphological
      criteria for glandular lesions were decreased cytoplasm, irregular nuclear
      membranes and the presence of nucleoli. CONCLUSION: The analysis of individual
      cyto-morphological criteria can better predict intraepithelial or invasive
      neoplasia and differentiate glandular from squamous lesions.

PMID- 16303044
TI  - Epidermal growth factor receptor and proliferating cell nuclear antigen
      expression in urine ThinPrep specimens.
AB  - OBJECTIVE: To evaluate proliferating cell nuclear antigen (PCNA) and epidermal
      growth factor receptor (EGFR) expression in urine ThinPrep (TP) specimens, to
      compare these findings with clinical and histological features and to determine
      whether these immunomarkers are predictive of clinical stage. PATIENTS AND
      METHODS: The TP processed urine samples and the corresponding tissue sections
      from 42 patients with newly diagnosed bladder cancer (18 non-muscle invasive and
      24 muscle invasive) were included in our study. Urine was collected for
      cytological evaluation before transurethral resection. Tumour grade and clinical
      stage were assessed from the transurethral resection specimens. The EGFR and PCNA
      expression was obtained by an automated immunostainer. RESULTS: There was a
      remarkable concordance in the expression of both antibodies in TP smears and
      tissue sections. No significant association was detected for any of the
      immunomarkers examined with regard to tumour grade. The EGFR expression as well
      as grade of malignancy were significantly associated with stage of disease (P =
      0.0001). PCNA was not found to be a significant predictor of stage (P = 0.210).
      CONCLUSION: Our data suggest that the evaluation of grade of malignancy and EGFR
      immunopositivity can be considered as reliable predictors of disease stage in
      urine TP specimens.

PMID- 16303045
TI  - Multiple visceral and subcutaneous nodules in a 4-month infant.

PMID- 16303046
TI  - Fine needle aspiration cytology of a non-ulcerated penile lump.

PMID- 16303047
TI  - Routine cervical cytology has no role after primary chemoradiation for cervical
      cancer.

PMID- 16303048
TI  - Microfilariae in cytology smears: real culprits or trapped accidentally by
      needles? A study of 10 cases.

PMID- 16303049
TI  - Micrococcus tetragenus: an unusual commensal in a cervical smear.

PMID- 16303050
TI  - Granular cell tumour of the subcutis: a cytological diagnosis.

PMID- 16303051
TI  - Activation of nuclear factor kappa B (NF-kappaB) by connective tissue growth
      factor (CCN2) is involved in sustaining the survival of primary rat hepatic
      stellate cells.
AB  - BACKGROUND/AIMS: Connective tissue growth factor (CCN2) is a matricellular
      protein that plays a role in hepatic stellate cell (HSC)-mediated fibrogenesis.
      The aim of this study was to investigate the regulation by CCN2 of cell survival
      pathways in primary HSC. METHODS: Primary HSC were obtained by in situ enzymatic
      perfusion of rat liver. NF-kappaB activation was assessed by immunoblotting for
      IkappaBalpha phosphorylation and degradation and by NF-kappaB p50 or p65 nuclear
      accumulation. NF-kappaB DNA-binding activity was determined by gel mobility shift
      assay while NF-kappaB response gene expression was evaluated using a luciferase
      reporter. Cell viability was assessed by Trypan blue staining or ATP luminescent
      assay while apoptosis was evaluated by caspase-3 activity. RESULTS: CCN2 induced
      IkappaBalpha phosphorylation and degradation as well as nuclear accumulation of
      NF-kappaB. Activated NF-kappaB comprised three dimers, p65/p65, p65/p50 and
      p50/p50, that individually bound to DNA-binding sites and subsequently triggered
      transcriptional activity. This was confirmed by showing that CCN2 promoted
      activity of a NF-kappaB luciferase reporter. CCN2 promoted survival of serum
      starved HSC and protected the cells from death induced by blocking the NF-kappaB
      signaling pathway using Bay-11-7082, a specific inhibitor of IkappaBalpha
      phosphorylation. CONCLUSION: CCN2 contributes to the survival of primary HSC
      through the NF-kappaB pathway.

PMID- 16303052
TI  - Review of the temporal and geographical distribution of measles virus genotypes
      in the prevaccine and postvaccine eras.
AB  - Molecular epidemiological investigation of measles outbreaks can document the
      interruption of endemic measles transmission and is useful for establishing and
      clarifying epidemiological links between cases in geographically distinct
      clusters. To determine the distribution of measles virus genotypes in the
      prevaccine and postvaccine eras, a literature search of biomedical databases,
      measles surveillance websites and other electronic sources was conducted for
      English language reports of measles outbreaks or genetic characterization of
      measles virus isolates. Genotype assignments based on classification systems
      other than the currently accepted WHO nomenclature were reassigned using the
      current criteria. This review gives a comprehensive overview of the distribution
      of MV genotypes in the prevaccine and postvaccine eras and describes the
      geographically diverse distribution of some measles virus genotypes and the
      localized distributions of other genotypes.

PMID- 16303053
TI  - Therapeutic lung lavages in children and adults.
AB  - BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare disease, characterized
      by excessive intra-alveolar accumulation of surfactant lipids and proteins.
      Therapeutic whole lung lavages are currently the principle therapeutic option in
      adults. Not much is known on the kinetics of the wash out process, especially in
      children. METHODS: In 4 pediatric and 6 adult PAP patients 45 therapeutic half
      lung lavages were investigated retrospectively. Total protein, protein
      concentration and, in one child with a surfactant protein C mutation, aberrant
      pro-SP-C protein, were determined during wash out. RESULTS: The removal of
      protein from the lungs followed an exponential decline and averaged for adult
      patients 2-20 g and <0.5 to 6 g for pediatric patients. The average protein
      concentration of consecutive portions was the same in all patient groups, however
      was elevated in pediatric patients when expressed per body weight. The amount of
      an aberrant pro-SP-C protein, which was present in one patient with a SP-C
      mutation, constantly decreased with ongoing lavage. Measuring the optical density
      of the lavage fluid obtained allowed to monitor the wash out process during the
      lavages at the bedside and to determine the termination of the lavage procedure
      at normal protein concentration. CONCLUSION: Following therapeutic half lung
      lavages by biochemical variables may help to estimate the degree of alveolar
      filling with proteinaceous material and to improve the efficiency of the wash
      out, especially in children.

PMID- 16303054
TI  - Phenytoin as a novel anti-vitiligo weapon.
AB  - Vitiligo is a psychologically devastating clinical conundrum which affects
      approximately 1% of the general population. The exact cause of the illness is an
      enigma, but several hypotheses about its pathogenesis are advanced. The
      autoimmune hypothesis proposes an autoimmune attack against melanocytes. Although
      anti-melanocyte autoantibodies have been demonstrated in vitiligo, recent
      research casts doubt on their pathogenic role and instead supports the
      involvement of cell-mediated autoimmune response in the pathobiology of this
      disorder, which is characterized by increase of suppressor T-cells and decrease
      of the helper/suppressor ratio in association with the presence of type-1
      cytokine secreting cytotoxic T cells in the vicinity of disappearing melanocytes.
      The neural hypothesis proposes that increased release of norepinephrine, a
      melanocytotoxin, from the autonomic nerve endings in the microenvironment of
      melanocytes injures these cells. Moreover, norepinephrine induces the
      catecholamine degrading enzyme monoamine oxidase (MAO), which favors the
      formation of toxic levels of hydrogen peroxide in the vicinity of melanocytes.
      Another theory suggests that abnormal permeability of melanosome membrane, which
      normally prevents the diffusion of toxic melanin precursors into the cytoplasm,
      may cause melanocyte damage. Phenytoin, the widely-used anticonvulsant, has been
      employed both topically and systemically in the treatment of some dermatological
      disorders. The drug has been shown to significantly suppress mitogen-induced
      activation of lymphocytes and cytotoxic T lymphocyte activity and to polarize the
      immune response toward the type-2 pathway. It also significantly decreases
      suppressor T cells and increases the helper/suppressor ratio. At high
      concentrations, the drug inhibits the release of norepinephrine and the activity
      of MAO. Moreover, phenytoin is suggested to interact with membrane lipids, which
      may promote stabilization of the membranes. The hydantoin moiety of phenytoin
      exerts a direct stimulatory action on melanocytes; facial hyperpigmentation is a
      recognized side effect of orally administered phenytoin. Altogether, the above
      evidence suggests that phenytoin could be therapeutically effective against
      vitiligo. As phenytoin stimulates collagen production and inhibits its breakdown,
      its concomitant use with topical steroids could prevent steroid-induced skin
      atrophy while potentiating the anti-vitiligo effect of these agents.

PMID- 16303056
TI  - Teratoma occupying the left hemithorax.
AB  - BACKGROUND: Teratomas are manifested with a great variety of clinical and
      radiological features, while sometimes they simply represent incidental findings.
      CASE PRESENTATION: A rare case of benign teratoma of the dermoid cyst type, in an
      adult 40-year-old female patient, is reported. The patient had presented
      recurrent pulmonary infections for the previous 2 months, persistent cough, and
      progressively aggravating dyspnea. A chest X-ray showed total atelectasis of the
      left lung, and the thoracic CT-scan revealed a huge mass, containing multiple
      elements of heterogeneous density, probably originating from the mediastinum,
      occupying the whole left hemithorax. The mass compressed the vital structures of
      the mediastinum, great vessels and airways, and a chest MRI was performed to
      accurately detect the anatomical relations. The patient underwent left
      thoracotomy and the tumor was totally resected. The size of the tumor was
      extremely large although no invasion to the vessels or to the airway had
      occurred. Adherence to the adjacent left pulmonary artery and left main bronchus
      was present, but without erosion or fistulization. The postoperative course was
      uneventful, while the histological examination confirmed a teratoma. CONCLUSION:
      A teratoma is a non-homogeneous pathological entity, clinically, radiologically
      or histologically. It is predominantly diagnosed between the second and fourth
      decade and the incidence is equal for both sexes. Symptoms are absent in one half
      of the patients. The case reported is noteworthy as the tumor appeared with total
      atelectasis of the left lung, and symptoms started 2 months prior to diagnosis.
      Total removal of the tumor is adequate treatment for this type of teratoma and
      the prognosis is excellent.

PMID- 16303055
TI  - Smoking, oxidative stress and inflammation: impact on resting energy expenditure
      in diabetic nephropathy.
AB  - BACKGROUND: Inflammation is associated with increased resting energy expenditure
      (REE) in patients with chronic kidney disease. Oxidative stress, on the other
      hand, appears not to increase REE. Smoking is a common mechanism for generating
      oxidative stress and inflammation. Whether smokers have increased REE and if so,
      whether it is accounted for by the pro-oxidant and inflammatory state is not
      known. METHODS: A case control study of 11 smokers and 24 non-smokers with overt
      diabetic nephropathy was performed to evaluate the chronic effect of smoking on
      REE. REE (indirect calorimetry), glomerular filtration rate (iothalamate
      clearance), markers of oxidative stress (urinary and plasma malondialdehyde
      (MDA), and protein carbonyls) and inflammation (C-reactive protein, tumor
      necrosis factor-alpha, interleukin-6) were measured on two occasions four months
      apart. RESULTS: Biomarkers of inflammation (C-reactive protein) and oxidative
      stress (urinary and plasma MDA) were increased in smokers. REE was increased in
      smokers, 24.3 kcal/kg/day compared to 21 kcal/kg/day (p = 0.009) in non-smokers.
      After adjusting for age, GFR, MDA, C-reactive protein, and hemoglobin A1C the
      difference in REE between the two groups persisted (adjusted difference 3.51
      kcal/kg/d, 95% confidence interval 0.59-6.45, p = 0.020). CONCLUSION: Patients
      with overt diabetic nephropathy who smoke have a higher REE, oxidative and
      inflammatory state. Elevated REE is not attributable to heightened oxidative
      stress and inflammatory state. Smoking is an independent risk factor for elevated
      REE in patients with diabetic nephropathy and provides an additional mechanism by
      which it may lead to poor outcomes.

PMID- 16303057
TI  - Expression and genomic organization of zonadhesin-like genes in three species of
      fish give insight into the evolutionary history of a mosaic protein.
AB  - BACKGROUND: The mosaic sperm protein zonadhesin (ZAN) has been characterized in
      mammals and is implicated in species-specific egg-sperm binding interactions. The
      genomic structure and testes-specific expression of zonadhesin is known for many
      mammalian species. All zonadhesin genes characterized to date consist of meprin
      A5 antigen receptor tyrosine phosphatase mu (MAM) domains, mucin tandem repeats,
      and von Willebrand (VWD) adhesion domains. Here we investigate the genomic
      structure and expression of zonadhesin-like genes in three species of fish.
      RESULTS: The cDNA and corresponding genomic locus of a zonadhesin-like gene (zlg)
      in Atlantic salmon (Salmo salar) were sequenced. Zlg is similar in adhesion
      domain content to mammalian zonadhesin; however, the domain order is altered.
      Analysis of puffer fish (Takifugu rubripes) and zebrafish (Danio rerio) sequence
      data identified zonadhesin (zan) genes that share the same domain order, content,
      and a conserved syntenic relationship with mammalian zonadhesin. A zonadhesin
      like gene in D. rerio was also identified. Unlike mammalian zonadhesin, D. rerio
      zan and S. salar zlg were expressed in the gut and not in the testes. CONCLUSION:
      We characterized likely orthologs of zonadhesin in both T. rubripes and D. rerio
      and uncovered zonadhesin-like genes in S. salar and D. rerio. Each of these genes
      contains MAM, mucin, and VWD domains. While these domains are associated with
      several proteins that show prominent gut expression, their combination is unique
      to zonadhesin and zonadhesin-like genes in vertebrates. The expression patterns
      of fish zonadhesin and zonadhesin-like genes suggest that the reproductive role
      of zonadhesin evolved later in the mammalian lineage.

PMID- 16303058
TI  - Chromosomal phylogeny of Robertsonian races of the house mouse on the island of
      Madeira: testing between alternative mutational processes.
AB  - The ancestral karyotype of the house mouse (Mus musculus) consists of 40
      acrocentric chromosomes, but numerous races exist within the domesticus
      subspecies characterized by different metacentric chromosomes formed by the
      joining at the centromere of two acrocentrics. An exemplary case is present on
      the island of Madeira where six highly divergent chromosomal races have
      accumulated different combinations of 20 metacentrics in 500-1000 years.
      Chromosomal cladistic phylogenies were performed to test the relative performance
      of Robertsonian (Rb) fusions, Rb fissions and whole-arm reciprocal translocations
      (WARTs) in resolving relationships between the chromosomal races. The different
      trees yielded roughly similar topologies, but varied in the number of steps and
      branch support. The analyses using Rb fusions/fissions as characters resulted in
      poorly supported trees requiring six to eight homoplasious events. Allowance for
      WARTs considerably increased nodal support and yielded the most parsimonious
      trees since homoplasy was reduced to a single event. The WART-based trees
      required five to nine WARTs and 12 to 16 Rb fusions. These analyses provide
      support for the role of WARTs in generating the extensive chromosomal
      diversification observed in house mice. The repeated occurrence of Rb fusions and
      WARTs highlights the contribution of centromere-related rearrangements to
      accelerated rates of chromosomal change in the house mouse.

PMID- 16303059
TI  - Psychotic-like experiences in the general community: the correlates of CIDI
      psychosis screen items in an Australian sample.
AB  - BACKGROUND: Apart from individuals with clinical psychosis, community surveys
      have shown that many otherwise well individuals endorse items designed to
      identify psychosis. The aim of this study was to characterize the demographic
      correlates of individuals who endorse psychosis screening items in a large
      general community sample. METHOD: The National Survey of Mental Health and
      Wellbeing interviewed 10641 individuals living in private dwellings in Australia.
      As part of a diagnostic interview (the CIDI), respondents were asked between
      three and six items originally designed to screen for potential psychosis. We
      examined the impact of selected demographic variables on endorsement of these
      items including sex, age, marital status, migrant status, urban/rural status,
      employment, education, and socio-economic status. RESULTS: An estimated 11.7% of
      the Australian population endorsed at least one psychosis-screening item.
      Significantly higher endorsement was associated with younger age, migrants from
      non-English-speaking backgrounds, those who had never married or who were
      divorced/separated or unemployed, those living in urban regions and those from
      the lowest socio-economic levels. CONCLUSIONS: Many of the correlates of
      endorsement of psychosis-screen items are also associated with psychosis.
      Unravelling the factors that contribute to this broader non-clinical phenotype
      will aid our understanding of psychosis.

PMID- 16303060
TI  - No evidence of time trends in the urban-rural differences in schizophrenia risk
      among five million people born in Denmark from 1910 to 1986.
AB  - BACKGROUND: There have been conflicting reports on time trends in urban-rural
      differences in the incidence of schizophrenia. This study explored the potential
      time trends in these differences with regard to birth cohort and age at onset.
      METHOD: Linking data from the Danish Civil Registration system with data from the
      Danish Psychiatric Central Register, a cohort born in Denmark from 1910 to 1986
      was established (5.05 million people). Overall, 23051 people were classified with
      schizophrenia in 1970-2001. RESULTS: Urban-rural differences in schizophrenia
      risk may have existed for people born in Denmark since 1910, and have existed at
      a constant level for people born from 1945 to 1986. Males aged <20 years had a
      risk of 3.90 [95% confidence interval (CI) 3.28-4.65] associated with urban birth
      while males >or=20 years had a risk of 2.12 (1.98-2.27). Females <20 years had a
      risk of 2.49 (95% CI 2.01-3.09) associated with urban birth while females >or=20
      years had a risk of 1.90 (95% CI 1.74-2.08). At age 46, 1.84% (95% CI 1.76-1.93)
      of males and 1.05% (95% CI 0.99-1.12) of females born in the capital area had
      developed schizophrenia, while 0.81% (95% CI 0.75-0.86) of males and 0.56% (95%
      CI 0.51-0.60) of females born in the rural area had developed schizophrenia.
      CONCLUSIONS: There was no evidence of time trends in the urban-rural differences
      in the incidence of schizophrenia in Denmark, suggesting that the cause(s)
      responsible for these differences were not related to exposures that became more
      prevalent in urban areas over time. This finding is in contrast to findings from
      Finland and The Netherlands.

PMID- 16303061
TI  - Ethno-psychometric evaluation of the General Health Questionnaire in rural China.
AB  - BACKGROUND: Most mental health research tools are developed in Western, urban
      contexts. Few studies have evaluated the applicability of these research tools in
      rural populations of non-Western countries. We examined the cultural acceptance
      and psychometric performance of the 12-item General Health Questionnaire (GHQ) in
      China's rural villages. METHOD: Ethnographic investigations were conducted to
      assess the cultural applicability of self-report rating scales among villagers.
      This was followed by a survey of 1401 rural residents, randomly selected from 48
      villages of Shandong province using stratified multistage cluster sampling. The
      respondents were administered the GHQ and the Composite International Diagnostic
      Interview (CIDI). RESULTS: The GHQ, when administered by trained interviewers,
      was culturally acceptable to rural residents. The scale had good psychometric
      properties in the study population. The area under the curve was 0.86. At a cut
      off of 1/2, the sensitivity and specificity were 80.6% and 79.3% respectively.
      CONCLUSIONS: The ethno-psychometric evaluation showed that the GHQ was both
      culturally valid and psychometrically sound in the Chinese rural context.

PMID- 16303062
TI  - A review on pelvic inflammatory disease.
AB  - Pelvic inflammatory disease (PID) remains a significant cause of morbidity
      worldwide, with the potential to result in serious reproductive complications.
      Much of the definitive work regarding PID was completed in the 1960s and 1970s.
      More recently, however, there have been a range of studies published that have
      contributed to our understanding of PID. Aetiologically, the main pathogens are
      chlamydia and gonorrhoea, but may include Mycoplasma genitalium and anaerobic
      Gram-negative rods. Risk factors associated with the development of PID include
      inconsistent barrier contraception, possibly vaginal douching, and the oral
      contraceptive pill likely masking the clinical severity of the disease. The small
      risk associated with the intrauterine device is limited to the first few weeks
      after insertion. New diagnostic techniques being evaluated include Doppler
      ultrasound and magnetic resonance imaging. Management must be prompt to prevent
      complications, and there are no apparent differences in clinical outcomes,
      whether treated as an inpatient or outpatient. Effective disease prevention
      includes widespread chlamydia screening and improving education.

PMID- 16303064
TI  - Biological false-positive tests comprise a high proportion of Venereal Disease
      Research Laboratory reactions in an analysis of 300,000 sera.
AB  - This retrospective study on syphilis screening at the sexually transmitted
      infection (STI) unit of a University Department emphasizes the necessity of a
      treponemal-specific test as the appropriate screening test. The Venereal Disease
      Research Laboratory (VDRL) test for syphilis screening may, under certain
      circumstances, yield positive results in patients not infected with Treponema
      pallidum, a phenomenon referred to as biological false-positive (BFP) VDRL test.
      The aim of this study was to determine the frequency of BFP tests in a large
      sample of sera. In this retrospective study, we analysed the results of parallel
      VDRL and T. pallidum haemagglutination (TPHA) testing of a total of 514,940 blood
      samples obtained from patients at the Vienna General Hospital between January
      1988 and November 1999. Patients' sera with incomplete data on stage and sex and
      duplicate sera were excluded, leaving 300,000 sera for analysis. The
      seroprevalence for syphilis was 1.77% (n = 5320), as determined by a positive
      TPHA test. It was significantly higher in male than in female patients (2.03%
      versus 1.58%, P<0.001). Of the patients reactive in the TPHA test, 3257 (61.2%)
      were negative in the VDRL. With regard to reactivity in VDRL testing, 2799
      patients (0.92%) of the study population were positive, of whom 736 (26%) were
      biological false positive. BFP reactivity was found in 0.24% of all patients and
      was significantly higher in women than in men (0.27% versus 0.20%, P<0.001) and
      in patients over 60 years of age (0.34%) as compared with those under 60 (0.25%,
      P<0.001). This proportion might be even higher, as reactivity in the VDRL at 1:0
      and 1:2 dilutions without a positive treponemal test was not reported. The
      subgroup of HIV-positive patients (n = 1415) revealed a 10-fold higher rate of
      BFP tests (2.1% versus 0.24), an effect being statistically significant. In a low
      syphilis prevalence population, BFP reactions comprise a high proportion of all
      VDRL reactors. Therefore, the use of the VDRL as a screening procedure is
      challenged.

PMID- 16303065
TI  - Self-sampling versus physician-sampling for human papillomavirus testing.
AB  - We evaluated the detection of human papillomavirus (HPV) infection using two
      sampling methods of cervical exfoliated cells, consisting of self-sampling of
      vaginal cells and cervical sampling performed by the physician. Women included
      were 379 patients of the general population attending outpatient clinics in
      Northern Greece for routine cytological cervical dysplasia screening. HPV DNA
      detection was similar with both sampling techniques. The HPV prevalences in self
      collected samples were 4.7% and 3.7% in the physician-collected samples (P>0.05).
      The Kappa statistic for HPV DNA agreement between the two methods was 0.54 (95%
      Confidence interval = 0.33-0.75). Self-sampling of cervico-vaginal exfoliated
      cells could be used as an alternative option to test for HPV infection.

PMID- 16303066
TI  - The three-year positivity rate of sexually transmitted infections among a group
      of HIV-infected men attending the Department of Genitourinary Medicine,
      Edinburgh, UK.
AB  - The aim of this study was to investigate the prevalence of sexually transmitted
      infections (STI) among patients at the time of and subsequent to the diagnosis of
      HIV, and possible immunological or virological features of patients with STI. An
      observational study was carried out on the results of annual STI screenings
      conducted on consecutive HIV-infected men in the Department of Genitourinary
      Medicine, Edinburgh between 1 January 1999 and 1 January 2003. Patients were
      tested for syphilis, gonococcal, and chlamydial infections. Among the 79 male
      patients in the study cohort, the frequencies of all STI rose within the study
      period. The three-year positivity rates of episodes of gonorrhoea, chlamydia, and
      syphilis were (42/131) 32%, (21/127) 16%, and (13/150) 9%, respectively. Patients
      with STI had significantly higher median CD4+ T-cells (P<0.02) and lower median
      viral loads (P<0.0001), and a higher proportion of them were on highly active
      anti-retroviral therapy (HAART) (P<0.0002) compared with those without an STI.
      Routine screening for STI and counselling for safe sex should be part of care for
      all HIV-infected patients.

PMID- 16303067
TI  - Chronic herpes simplex virus type-2 infection and HIV viral load.
AB  - By December 2003, the estimated adult HIV/AIDS prevalence rate in sub-Saharan
      Africa was 7.5-8.5%, and rates of herpes simplex virus type-2 (HSV-2) infection
      among adults aged >30 years ranged from 60% to 82%. However, little is known
      about the natural history of HIV/HSV-2 co-infection in this population. We
      evaluated HIV viral load and CD4+ cell counts among persons with and without
      chronic HSV-2 co-infection in a cross-sectional study of HIV-infected persons not
      receiving antiretroviral therapy. HSV-2 and HIV co-infection was associated with
      a 0.3 log copies/mL higher HIV viral load compared with persons without HSV-2
      infection (P=0.014). Chronic HSV-2 infection may have a negative effect on the
      clinical course of persons with HIV.

PMID- 16303068
TI  - Recurrent bacterial vaginosis: the use of maintenance acidic vaginal gel
      following treatment.
AB  - Bacterial vaginosis (BV) frequently recurs after treatment. One option in the
      management of recurrences is to keep the vaginal pH at 4.5 or less, in order to
      prevent overgrowth of bacteria, until the normal lactobacilli are re-established.
      We report the outcome of using maintenance acetic acid vaginal gel, after
      treatment of BV, in a sample of 49 women with frequent recurrences. Half of the
      women had no further recurrences, and in those who did there was a significant
      increase in time to first recurrence (4.8 months) after commencing the gel
      compared with the previous recurrence (2.1 months). Prior to using acidic gel,
      the mean recurrence rate in 49 women was 4.4 per woman/year, and this was reduced
      to 0.6 recurrences per woman/year. As there are few effective therapies for women
      with recurrent BV, we feel this offers an option that can currently be used in
      clinical practice.

PMID- 16303069
TI  - Reported condom use and condom use difficulties in street outreach samples of men
      of four racial and ethnic backgrounds.
AB  - The epidemiology of the HIV/AIDS epidemic in the United States has focused
      research attention on lesbian, gay, bisexual and transgendered communities as
      well as on racial and ethnic minorities. Much of that attention has, however,
      been focused on specific racial and ethnic groups, and specific sexual
      minorities. We report on the results of a study that examined the association
      between condom use and partnership types among men from four major racial/ethnic
      groups. Self-reported data on sexual identity (homosexual, bisexual, and
      heterosexual) and condom use in the past three months were collected from 806
      African Americans, Hispanic, Asian, and white men intercepted in public places in
      Houston, TX. Data indicated that condom use was lowest in African Americans and
      Hispanic men, bisexual men reported the highest levels of use, with heterosexual
      men reporting the lowest use. African Americans and Hispanic men reported
      generally that it was very difficult to use a condom during sexual contact,
      although the patterns for self-identified homosexual, heterosexual, and bisexual
      men varied across race/ethnicity. Homosexual African American men reported the
      least difficulty, and white homosexual men the most difficulty compared with
      heterosexual and bisexual peers. For homosexually identified men, there were
      considerable differences across race/ethnicity in the proportion of partners who
      never or rarely disagreed to use condoms, with Asians disagreeing least, and
      African Americans most. Within racial/ethnic groups, the levels of condom use and
      difficulty were similar for male and female partners, suggesting that it is
      sexual identity, rather than partner gender, that has impacted condom-use
      messages. These data suggest that racial/ethnic targeting of condom use is likely
      to be most efficacious in increasing condom use in men.

PMID- 16303070
TI  - Male sex workers in Antwerp, Belgium: a descriptive study.
AB  - The objective of this study was to describe the prevalence of sexually
      transmitted infections (STI), sociodemographic and behavioural characteristics in
      a population of male sex workers (MSW) in Antwerp, Belgium. Between September
      1999 and March 2004, 129 MSW were reached by Gh@pro, an outreach programme
      providing preventive health care, free STI check-up and hepatitis B vaccination,
      to sex workers (SW). Sera were collected from 121 men, urine samples from 115 men
      and a questionnaire was filled in by 43 MSW. In 45.5% of MSW one or more STI were
      diagnosed (including hepatitis B), 76% on laboratory testing at first screening,
      9% through symptomatology at first visit. The prevalence of HIV was 10.8%,
      hepatitis B virus (HBV) infection 28.9%, syphilis 12.5%, gonorrhoea 1.7% and
      Chlamydia trachomatis 9.7%. More than 50% of non-immune MSW completed their three
      dose hepatitis B vaccination course. Prevalence of STI is concordant with
      published data on MSW; this population clearly requests and deserves particular
      attention and approach. There is an important difference in sociodemographic and
      behavioural characteristics between MSW working in the red light district and
      those working on the street. Health promotion should be tailored to the different
      subpopulations and outreach appears to be a successful tool.

PMID- 16303071
TI  - Hepatitis C virus infection, HIV co-infection, and associated risk among
      injecting drug users in Togliatti, Russia.
AB  - The objective of this study was to estimate the prevalence of hepatitis C virus
      (HCV) infection and co-infection with HIV among injecting drug users (IDUs) in
      Togliatti City, Russia. Unlinked anonymous cross-sectional survey of IDUs
      recruited from community settings, with oral fluid sample collection for HCV and
      HIV antibody (anti-HCV, anti-HIV) testing, was carried out. The anti-HCV
      prevalence was 87% (357/411), anti-HIV prevalence 56% (234/418), and 93%
      (214/230) of HIV-positive IDUs were co-infected with HCV. Only 23% (94/411) of
      those HCV positive self-reported as such. In an adjusted model, increased odds of
      HCV positivity were associated with needle and syringe, as well as injecting
      paraphernalia sharing in the last four weeks. IDUs injecting more than once with
      the same needle also had raised odds. There were no marked associations between
      HCV positivity and the duration of injecting or age group. Almost all IDUs were
      HCV positive, and almost all HIV-positive IDUs were HCV co-infected. There is an
      urgent need to maximize syringe distribution coverage, develop health promotion
      targeting HCV prevention for IDUs, and improve access among IDUs to treatments
      for HIV and HCV infection.

PMID- 16303072
TI  - The feasibility of voluntary counselling and HIV testing for pregnant women using
      community volunteers in Zimbabwe.
AB  - The purpose of this pilot project was to assess the feasibility and acceptability
      of voluntary counselling and HIV testing (VCT) by pregnant women using community
      volunteers in Zimbabwe to prevent mother to child transmission (MTCT) of HIV.
      From July 1999 to June 2001, a short-course zidovudine (ZDV)-based perinatal HIV
      prevention programme was initiated in two antenatal clinics. Community
      volunteers, recruited from local community organizations, underwent a two-week
      training course in VCT, which included HIV/AIDS facts, systematic counselling
      approach, and practical counselling techniques using scripts and role-play. Rapid
      HIV testing was performed after informed consent. Lay counsellors conducted
      individual pre- and post-test counselling for HIV. A total of 35 women community
      volunteers were trained in VCT; 34 graduated and committed to work four hours per
      week in the clinic. Of the 6051 pregnant women presenting for antenatal clinics
      (ANC), 1824 (30%) underwent pre-test counselling and 1547 (26%) were tested, and
      429 (28%) were HIV infected. Overall, 1283 (83%) returned for their test results
      including 406 (95%) of HIV-infected women. Of the 406 HIV-infected women who
      collected their test results, only 203 (50%) opted for ZDV prophylaxis to prevent
      MTCT of HIV. Over the two-year study period, two counsellors died and three
      sought employment at other organizations. Adherence to duty roster was 97% and no
      breach of confidentiality was reported. Despite many challenges, VCT delivered by
      community volunteers is feasible and acceptable for pregnant women aiming to
      reduce their risk of transmitting HIV to their infants. This programme is being
      implemented at several urban and rural MTCT sites in Zimbabwe and can serve as a
      model for other resource-poor countries.

PMID- 16303073
TI  - Management of recurrent genital herpes: a survey of UK genitourinary medicine
      clinics in 2003.
AB  - We carried out a survey of all UK genitourinary (GU) medicine clinics, via postal
      questionnaire, in order to evaluate the current management of recurrent genital
      herpes (RGH) in the GU medicine setting. Respondents were invited to answer
      questions regarding various aspects of herpes simplex virus (HSV) management.
      There was a 62% response rate. Analysis of the returned surveys revealed that the
      vast majority of clinics (96%) provided drug treatment for RGH, with 81% having a
      clinic policy for the management of genital herpes (GH). A majority (64%) of
      clinics had access to some type of counselling or psychological therapy and 47%
      encouraged collaboration with primary care for follow-up prescribing. Of the
      clinics providing drug therapy for RGH, 80% used aciclovir alone with smaller
      numbers having access to aciclovir, famciclovir and valaciclovir. While many
      clinics are meeting the British Association of Sexual Health and HIV (BASHH)
      guidelines, improvements can be made to increase the availability of
      psychological support to patients with HSV and improve links with primary care.

PMID- 16303074
TI  - Pneumonia complicating Shigella sonnei dysentery in an HIV-infected adult male.
AB  - An HIV-1-infected adult presented with a short history of dyspnoea, productive
      cough and myalgia with fever. Shortly after presentation, he developed the abrupt
      onset of high-volume watery diarrhoea: stool culture grew Shigella sonnei. At the
      same time, he became hypoxaemic, and thoracic imaging showed bilateral lower lobe
      consolidation/collapse. Culture of sputum and blood was negative. The patient
      recovered with fluid resuscitation and ciprofloxacin monotherapy. This is the
      first reported case of pneumonia complicating S. sonnei dysentery in an HIV
      infected adult.

PMID- 16303075
TI  - A case of penile superficial basal cell carcinoma involving the inner surface of
      foreskin.
AB  - Basal cell carcinoma accounts for most skin malignancies. Genital basal cell
      carcinoma, however, is very rare. We report the first case of superficial basal
      cell carcinoma involving the inner surface of foreskin. Shared expertise within a
      multidisciplinary clinic was necessary for early diagnosis of the present case.

PMID- 16303076
TI  - Mycoplasma genitalium and asymptomatic chlamydia-negative non-gonococcal
      urethritis revisited.

PMID- 16303077
TI  - Neuropsychiatric effects of efavirenz: delayed onset.

PMID- 16303078
TI  - Asymptomatic urethritis needs to be defined and the value of its diagnosis
      measured.

PMID- 16303079
TI  - Routine screening of asymptomatic men for Chlamydia trachomatis-negative
      urethritis.

PMID- 16303080
TI  - Red urine in a returning traveller.

PMID- 16303081
TI  - Lymphogranuloma venereum and genital ulceration.

PMID- 16303082
TI  - Treatment of genital lichen sclerosus with topical calcipotriol.

PMID- 16303083
TI  - Why no accessible condom-vending machines in UK high streets?

PMID- 16303084
TI  - Lichen sclerosus: are there really no long-term disturbances in sexual function?

PMID- 16303087
TI  - New insights into the post-translational modification of Toll-like receptor
      signaling molecules.
AB  - Deregulation of Toll-like receptor (TLR) mediated responses can have devastating
      effects on the host if left unchecked. It is, therefore, critical that control is
      exerted at several levels. In this review, we discuss post-translational
      modification of TLRs and their associated signaling molecules as one such means
      of control. In particular, we focus on the phosphorylation, ubiquitination and de
      ubiquitination of various components of TLR signaling pathways.

PMID- 16303088
TI  - Mutations in TLR4 signaling that lead to increased susceptibility to infection in
      humans: an overview.
AB  - In this overview, we will present current information on known mutations in the
      TLR4 signaling pathway that have been associated with increased susceptibility to
      disease. To date, mutations in the extracellular domain of TLR4 itself, IRAK-4,
      NEMO (IKK gamma), and I kappa B alpha have been identified and profoundly affect
      the host response to infection.

PMID- 16303089
TI  - Synthesis of lipid A and its analogues for investigation of the structural basis
      for their bioactivity.
AB  - As a step to elucidate the structural requirements for the endotoxic and
      antagonistic activity of lipid A derivatives, we have focused, in the present
      study, on the effects of the acyl moieties and acidic groups at the 1- and 4'-
      positions. We synthesized a new analogue corresponding to Rubrivivax gelatinosus
      lipid A, which has a characteristic symmetrical distribution of acyl groups on
      the two glucosamine residues with shorter acyl groups (decanoyl groups [C(10)]
      and lauryl groups [C(12)]) than Escherichia coli lipid A. Carboxymethyl analogues
      in which one of the phosphates was replaced with a carboxymethyl group were also
      synthesized with different distribution of acyl groups. Biological tests revealed
      that the distribution of acyl groups strongly affected the bioactivity. The
      synthetic Ru. gelatinosus type lipid A showed potent antagonistic activity
      against LPS, whereas its 1-O-carboxymethyl analogue showed weak endotoxic
      activity. These results demonstrated that when the lipid A has shorter (C(10),
      C(12)) hexa-acyl groups, the bioactivity of lipid A is easily affected with small
      structural difference, such as the difference of acidic group or the distribution
      of acyl groups, and the bioactivity changes from endotoxic to agonistic or vice
      versa at this structural boundary for the bioactivity. We also designed, based on
      molecular mechanics calculations, and synthesized lipid A analogues possessing
      acidic amino acid residues in place of the non-reducing end phosphorylated
      glucosamine. Definite switching of the endotoxic or antagonistic activity was
      also observed depending on the difference of the acidic groups (phosphoric acid
      or carboxylic acid) in the lipid A analogues.

PMID- 16303090
TI  - Structure/function relationships of lipoteichoic acids.
AB  - The role of lipoteichoic acids (LTAs) from Gram-positive bacteria as
      immunostimulatory molecules was controversial for many years, as inadequate
      preparation methods as well as heterogeneous and endotoxin-contaminated
      commercial preparations led to conflicting results. An improved purification
      methodology for LTA now yields potent bioactive and chemically defined material,
      which is currently being characterized in various models. A synthetic analogue of
      Staphylococcus aureus LTA has proven the structure/function relationship. The key
      role of D-alanine esters for the immune response of LTA was confirmed by
      synthetic derivatives. The glycolipid anchor of LTA plays a central role
      analogous to the lipid A of LPS. Methodological aspects and criteria for quality
      assessment of LTA preparations are discussed.

PMID- 16303091
TI  - Role of surfactant protein D (SP-D) in innate immunity in the gastric mucosa:
      evidence of interaction with Helicobacter pylori lipopolysaccharide.
AB  - Surfactant protein D (SP-D) is a collagenous glycoprotein, a collectin, which
      functions as a pathogen-associated molecular pattern (PAMP) recognition receptor
      in the innate immune response. Although originally identified in the lung as a
      component of surfactant, SP-D also occurs in the gastric mucosa at the luminal
      surface and within gastric pits of mucus-secreting cells. Infection with the
      gastroduodenal pathogen Helicobacter pylori up-regulates expression of SP-D in
      human patients with gastritis, and its influence on colonization has been
      demonstrated in a Helicobacter SP-D-deficient (SP-D(-/-)) mouse model. SP-D binds
      and agglutinates H. pylori cells in a lectin-specific manner, and has been shown
      to bind H. pylori lipopolysaccharide. Furthermore, evidence indicates that H.
      pylori varies LPS O-chain structure to evade SP-D binding which is speculated
      aids persistence of this chronic infection.

PMID- 16303092
TI  - Inhibition of TLR-4/MD-2 signaling by RP105/MD-1.
AB  - Activation of Toll-like receptor (TLR) signaling by microbial and host molecular
      signatures is critical to the induction of immune responses. Such signaling is,
      perforce, kept under tight control. We recently discovered a novel endogenous
      inhibitor of TLR-4 - RP105. Initially identified as a B-cell-specific molecule
      with a role in B-cell proliferation in response to RP105 mAb and LPS, RP105 is a
      TLR-4 homologue. Further, like TLR-4 whose surface expression and signaling
      depends upon co-expression of the secreted protein MD-2, surface expression of
      RP105 is dependent upon co-expression of the MD2 homologue, MD-1. Unlike the
      TLRs, however, RP105 lacks a signaling domain, having the apparent structure of a
      TLR inhibitor. Further, RP105 is not B-cell-specific; its expression directly
      mirrors that of TLR-4 on dendritic cells and macrophages. These considerations
      suggested a role for RP105 as a physiological inhibitor of TLR-4 signaling.
      Indeed, we have recently found that: (i) RP105 is a specific inhibitor of TLR-4
      signaling in HEK293 cells; (ii) RP105/MD-1 interacts directly with TLR-4/MD-2,
      inhibiting the ability of this signaling complex to bind LPS; (iii) RP105
      regulates TLR-4 signaling in dendritic cells and macrophages; and (iv) RP105
      regulates in vivo responses to LPS.

PMID- 16303093
TI  - Antibodies against human Toll-like receptors (TLRs): TLR distribution and
      localization in human dendritic cells.
AB  - We have produced monoclonal antibodies (mAbs) against human Toll-like receptors
      (TLRs). These mAbs recognize the natural conformation of the extracellular domain
      leucine-rich repeats and, thereby, are suitable for immunoprecipitation, flow
      cytometric analysis and immunostaining. Using these mAbs, we determined the
      distribution of TLRs in a variety of human cell populations. Human TLRs that
      recognize bacterial components, particularly TLR-1, TLR-2, TLR-4 and TLR-6,
      reside on the cell surface and are expressed in myeloid and monocyte-derived
      dendritic cells (DCs) but not in plasmacytoid DCs (pDCs). Human TLR-3 resides in
      putative endosomes in myeloid DCs. Thus, the human myeloid DC subset harbors a
      unique and distinctive TLR repertoire. These mAbs will be useful to test the
      localization and distribution of human TLRs in a variety of cells and organs.
      Functional studies of human TLRs will also be feasible since certain of them are
      function-blocking mAbs.

PMID- 16303094
TI  - The role and regulation of apoptosis in sepsis.
AB  - Today, sepsis continues to be a growing problem in the critically ill patient
      population. A number of laboratories have been interested in understanding how
      changes in immune cell apoptosis during sepsis appear to contribute to septic
      morbidity. Consistently, it has been found that immune cell apoptosis is altered
      in a variety of tissue sites and cell populations both in experimental animals
      and humans. While divergent mediators, such as steroids and TNF, contribute to
      some of these apoptotic changes, their effects are tissue and cell population
      selective. Inhibition of FasL-Fas signaling (by either FasL gene deficiency, in
      vivo gene silencing [siRNA] or with FasL binding protein) protects septic mice
      from the onset of marked apoptosis and the morbidity/mortality seen in sepsis.
      Further, this extrinsic apoptosis response appears to utilize aspects of the Bid
      induced mitochondrial pathway. This is in keeping with the findings that pan
      specific caspase inhibition or the overexpression of Bcl-2 also protect these
      animals from the sequellae of sepsis.

PMID- 16303096
TI  - How Toll-like receptors and Nod-like receptors contribute to innate immunity in
      mammals.
AB  - Innate immune detection of pathogens relies on specific classes of microbial
      sensors called pattern-recognition molecules (PRM). In mammals, such PRM include
      Toll-like receptors (TLRs) and the intracellular proteins NOD1 and NOD2, which
      belong to the family of Nod-like receptors (NLRs). Over the last decade as these
      molecules were discovered, a function in innate immunity has been assigned for
      the majority of them and, for most, the microbial motifs that these molecules
      detect were identified. One of the next challenges in innate immunity is to
      establish a better understanding of the complex interplay between signaling
      pathways induced simultaneously by distinct PRMs and how this affects tailoring
      first-line responses and the induction of adaptive immunity to a given pathogen.

PMID- 16303095
TI  - Peptidoglycan recognition by the Drosophila Imd pathway.
AB  - The structural requirements for recognition of peptidoglycan (PGN) by PGRP-LC and
      activation of the Drosophila IMD pathway are not yet clear. In order to examine
      this question more carefully, the activity of peptidoglycan from different types
      of bacteria was compared in cell-based and whole animal assays. Drosophila S2*
      cells, but not adult flies, responded to Lys-type Micrococcus luteus PGN, but
      with significantly less potency compared to Dap-type Escherichia coli PGN, while
      intact Lys-type PGN from Staphylococcus aureus was inactive. After treatment with
      lysostaphin, which digests the cross-bridging peptides, S. aureus PGN weakly
      stimulated the IMD pathway, similar to M. luteus PGN. Further digestion with
      mutanolysin, which creates monomeric PGN fragments, abolished the activity of S.
      aureus PGN. On the other hand, monomeric E. coli PGN, generated by mutanolysin
      digestion, was still active but required different isoforms of PGRP-LC for
      recognition. Polymeric PGN required only PGRP-LCx, while monomeric E. coli PGN
      required both the PGRP-LCa and PGRP-LCx isoforms. These results suggest that the
      recognition by PGRP-LCx alone requires polymeric PGN, and that polymeric Dap-type
      PGN is a more potent PGRP-LCx agonist, compared to Lys-type PGN. These results
      also suggest that the heteromeric PGRP-LCa/LCx receptor complex recognizes
      monomeric Dap-type, but not Lys-type, PGN.

PMID- 16303097
TI  - Evidence for the requirement for CD40-CD154 interactions in resistance to
      infections with attenuated Salmonella.
AB  - Salmonella species include facultative intracellular pathogens which reside
      preferentially within cells of the host's reticulo-endothelial system. Resistance
      to Salmonella involves a collaboration between cells of the innate and adaptive
      immune systems, and protective immunity requires cell-mediated and humoral-immune
      responses. CD40-CD154 interactions are of central importance in the induction of
      cellular immune responses. In the present study, CD154-deficient (CD154(-/-))
      mice were used to assess the role of CD40-CD154 interactions in immunity to
      Salmonella infection. Compared to C57BL/6 (CD154(+/+)) controls, CD154(-/-) mice
      were hypersusceptible to infection by an attenuated strain of Salmonella enterica
      serovar Typhimurium (S. typhimurium), as evidenced by a significantly decreased
      survival rate. CD154(-/-) mice exhibited a defect in the production of IFN-gamma
      and NO in the acute phase of the disease, which resulted in a failure to control
      bacterial replication. We conclude that intercellular communications via the CD40
      CD154 pathway play a critical role in the induction type-1 cytokine responses and
      protection against primary infections with attenuated Salmonella.

PMID- 16303098
TI  - The clinical and cost-effectiveness of left ventricular assist devices for end
      stage heart failure: a systematic review and economic evaluation.
AB  - OBJECTIVES: To assess the clinical and cost-effectiveness of left ventricular
      assist devices (LVADs) as a bridge to heart transplantation (BTT), as a bridge to
      myocardial recovery (BTR) or as a long-term chronic support (LTCS) for people
      with end-stage heart failure (ESHF). DATA SOURCES: For the systematic review,
      electronic databases and bibliographies of related publications plus experts and
      manufacturers. For the economic evaluations, data originated from the systematic
      review of clinical and cost-effectiveness, UK hospitals, device manufacturers and
      expert opinion. REVIEW METHODS: For the systematic review, studies were selected
      and assessed against a set of rigorous criteria; data were then synthesised using
      a narrative approach through subgroup analysis based on the indication for
      treatment, type of LVAD and quality of studies. The economic evaluation developed
      two models to evaluate the use of LVADs, first as a BTT and second as LTCS for
      patients suffering from ESHF. RESULTS: Sixteen studies assessed the clinical
      effectiveness of LVADs as a BTT. Despite the poor methodological quality of the
      evidence, LVADs appeared beneficial compared to other treatment options (i.e.
      inotropic agents or usual care) or to no care (i.e. the natural history of ESHF)
      improving the survival of people with ESHF during the period of support and
      following heart transplantation. Patients supported by an LVAD appeared to have
      an improved functional status compared with those on usual care and experienced
      an improvement in their quality of life from before device implantation to the
      period during support. Serious adverse events are a risk for patients with an
      LVAD. With a scarcity of evidence directly comparing different devices, it is
      difficult to identify specific devices as the most clinically effective. The
      HeartMate LVAD is the only device that has evidence comparing it with the
      different alternatives, appearing to be more clinically effective than inotropic
      agents and usual care and as clinically effective as the Novacor device. Second
      generation devices, such as Jarvik 2000 and MicroMed Debakey LVADs, are early in
      their development but show considerable promise that should be assessed through
      long-term studies. Evidence of the clinical effectiveness of LVADs as a BTR was
      limited to seven non-comparative observational studies that appeared to show that
      the LVADs were beneficial in providing support until myocardial recovery. It was
      not possible to assess whether the LVADs are more effective than other
      alternatives or specific devices. No evidence was found on the quality of life or
      functional status of patients and limited information on adverse events was
      reported. Six studies assessed the clinical effectiveness of LVADs as an LTCS and
      from these it was evident that LVADs provided benefits in terms of improved
      survival, functional status and quality of life. Nineteen studies assessed the
      costs and cost-effectiveness of LVADS for people with ESHF, with the majority
      being simple costing studies and very few studies of the cost-effectiveness of
      LVADs. With no relevant cost-effectiveness studies available, an economic
      evaluation for BTT and LTCS was developed. The economic evaluation has shown that
      neither LVAD indication considered, that is, BTT and LTCS, is a cost-effective
      use. For the HeartMate LVAD used as a BTT the cost per QALY was pound 65,242. In
      the less restrictive indication, LTCS, where LVADs are not just given to patients
      awaiting transplantation, the analysis has shown that LTCS is not cost-effective.
      The baseline cost per QALY of the first-generation HeartMate LVAD was pound
      170,616. One- and multi-way sensitivity analysis had limited effect on the cost
      per QALY. A hypothetical scenario based on the cost of a second-generation
      MicroMed DeBakey device illustrated that a 60% improvement in survival over first
      generation devices was necessary before the incremental cost-effectiveness
      approached pound 40,000 per QALY. CONCLUSIONS: Although the review showed that
      LVADs are clinically effective as a BTT with ESHF, the economic evaluation
      indicated that they are not cost-effective. With the limited and declining
      availability of donor hearts for transplantation, it appears that the future of
      the technology is in its use as an LTCS. Further research is needed to examine
      the clinical effectiveness of LVADs for people with ESHF, assessing patient
      survival, functional ability, quality of life and adverse events. Evaluations of
      the clinical effectiveness of LVADs should include economic evaluations, as well
      as data on quality of life, utilities, resources and costs. A systematic review
      of the epidemiology of ESHF should be undertaken to assess its potential impact.

PMID- 16303099
TI  - The effectiveness of the Heidelberg Retina Tomograph and laser diagnostic
      glaucoma scanning system (GDx) in detecting and monitoring glaucoma.
AB  - OBJECTIVES: To determine the potential of optic nerve head tomography [Heidelberg
      Retina Tomograph (HRT)] and scanning laser polarimetry (GDx) for identifying
      patients with glaucomatous visual field loss. DESIGN: Examinations were performed
      with the HRT, GDx and Humphrey Field Analyzer (HFA). Glaucoma was defined by the
      presence of a field defect. Patients within the cross-sectional groups underwent
      a single examination, whereas patients in the longitudinal groups were examined 6
      monthly, for an average of 3.5 years. SETTING: Manchester Royal Eye Hospital, UK.
      PARTICIPANTS: Patients with primary open angle glaucoma (POAG) or who were at
      risk of developing glaucoma. INTERVENTIONS: The diagnostic accuracies of the HRT
      and GDx were compared; specificity was set at 95%. The rate of change was
      determined by linear regression. To estimate the clinical application of the
      instruments, the proportion of an unselected group of patients on whom the
      examinations could be performed was calculated. Additionally, the time taken to
      perform and process each examination was measured. MAIN OUTCOME MEASURES: The
      ability of the techniques to identify cases showing deterioration. The level of
      agreement and applicability of the techniques. Time taken to perform and process
      each examination. RESULTS: From the cross-sectional group, the maximum
      sensitivities of the HRT and GDx were 59% and 45%, respectively (at 95%
      specificity). From the two longitudinal cohorts, the level of agreement between
      the three instruments for identification of the development and deterioration of
      POAG was low. The applicability of the techniques was 80% (HRT), 88% (GDx) and
      98% (HFA). The length of time to perform a full examination with each instrument
      was 12.3, 11.8 and 28.3 minutes, respectively. Agreement of HRT and GDx
      parameters between and within observers was largely good. CONCLUSIONS: There is
      poor agreement for detection of glaucoma between the HFA, HRT and GDx. The
      techniques are amenable to use in the clinical environment, but no single
      examination has sufficient diagnostic precision to be used in isolation; also,
      the imaging techniques were not universally applicable. Neither the HRT nor GDx
      should be viewed as a replacement for visual field examination. Further research
      is needed into why most patients within the longitudinal arms of the study showed
      very little deterioration and into determining aspects of the structure versus
      function relationship in glaucoma that may explain why any one technique fails to
      detect a proportion of cases.

PMID- 16303100
TI  - Autoimmune mechanisms in children with systemic lupus erythematosus.
AB  - Although the pathogenesis of SLE remains poorly understood, there is consensus
      that it involves a combination of genetic, hormonal, and environmental factors.
      New technologies applied to genomic and gene expression studies have revealed
      novel gene mutations and cytokine alterations in this disease. Recently, advances
      in monoclonal antibodies and recombinant DNA technology have resulted in the
      development of new drugs to arrest disease progression and restore physiologic
      immune responses without major side effects. Clinical trials to test several of
      these novel therapies are currently underway.

PMID- 16303101
TI  - Blau syndrome and related genetic disorders causing childhood arthritis.
AB  - Blau Syndrome (BS) is an inheritable disorder characterized by granulomatous
      polyarthritis, panuveitis, and exanthema. It was described by Edward Blau in
      1985, the same year in which Douglas Jabs reported a very similar family.
      Clinically indistinguishable from early onset sarcoidosis (EOS), both are now
      known to share a mutated form of caspase recruitment domain-15 (CARD 15), a
      protein involved in activation of nuclear factor kappa B which is in turn an up
      regulator of pro-inflammatory cytokine transcription. An association between BS
      and EOS was suspected for years given the striking similarities of the core triad
      (arthritis-uveitis-dermatitis) and a common emerging pattern of systemic
      involvement. Hence, the familial form (BS) and the sporadic form (EOS) are almost
      certainly the same illness/defect, inherited in the first and acquired in the
      second as a result in most cases of a de novo mutation. Another form of
      granulomatous arthritis with uveitis, Crohn's disease, has also been associated
      with mutations in CARD 15 (albeit at a different domain) and despite similar
      phenotypes there are obvious differences including gut inflammation and pyoderma
      gangrenosum in Crohn's disease. This paper will review the clinical
      characteristics of these three disorders and their association with mutations in
      the CARD 15 gene.

PMID- 16303102
TI  - The use of anakinra in juvenile arthritis.
AB  - Interleukin-1 (IL-1), one of the major pro-inflammatory cytokines, plays an
      important role in the pathophysiology and progression of adult and pediatric
      arthritis. Inhibiting IL-1 activity by using a recombinant human IL-1 receptor
      antagonist (anakinra) given alone or in combination with methotrexate, moderately
      reduced the signs and symptoms of active arthritis in adults and slowed the rate
      of radiographic destruction. Preliminary results from an open label portion of a
      trial in children with polyarticular arthritis show similar outcomes with 58% of
      children exhibiting clinical improvements based on the Juvenile Arthritis 30%
      Core Set Criteria. The drug has an overall favorable safety profile and injection
      site reactions are the most commonly reported adverse event in both groups.
      However despite its rather disappointing effect in polyarticular arthritis,
      anakinra is being discovered as an effective treatment of systemic arthritis and
      children with mutations in the NALP3/CIAS1/PYPAF1 genes leading to autoimmune
      inflammatory disorders such as neonatal- onset multisystem inflammatory disease.

PMID- 16303103
TI  - Long-term outcomes in juvenile dermatomyositis: how did we get here and where are
      we going?
AB  - Juvenile dermatomyositis (JDM) affects two to four children per million. Prior to
      treatment with corticosteroids, JDM had a high mortality rate (> 30%) and left
      50% of those who survived with serious permanent impairments. After the
      introduction of corticosteroids, mortality rapidly dropped to less than 10%, and
      is currently reported to be less than 2% to 3%. Because most children now survive
      this illness, there is greater interest in long term outcomes. However, review of
      the literature shows while much is known about mortality, relatively little is
      known about long term outcomes such as physical function, quality of life, pain,
      educational and vocational achievement, patient satisfaction, and ongoing disease
      activity. Furthermore, the literature that has been published has not typically
      used the same outcomes making comparisons across studies difficult. Current
      efforts to identify key outcomes and validate measures for those outcomes will
      allow researchers in the future to provide this much needed information.

PMID- 16303104
TI  - Quality of life in children with systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) in children is a chronic multi-system disease
      with wide ranging effects on their quality of life (QOL). While SLE's impact on
      different arenas of life and well-being has been extensively examined in the
      adult population, its effect on children has not received adequate attention.
      This paper briefly discusses the multidimensional aspect of QOL, the
      biopsychosocial implications of SLE, factors complicating QOL measurement in the
      affected population, and the different generic and disease-specific scales used
      for measuring QOL and related constructs, and it also highlights the need for SLE
      specific pediatric QOL instruments.

PMID- 16303105
TI  - Hormone therapy in systemic lupus erythematosus.

PMID- 16303106
TI  - New therapies and preventive strategies to treat and minimize damage in lupus.
AB  - Systemic lupus erythematosus is a complex disease characterized by a loss of
      immune tolerance leading to autoantibody production, immune complex deposition in
      target organs, and resultant tissue damage. There are currently only three
      medications approved for the treatment of lupus; hydroxychloroquine, aspirin, and
      prednisone. This limited spectrum of medications is contrasted by the dozen
      clinical trials in lupus underway or planned for the next 2 years. These new
      therapeutic agents hold promise for being more effective with fewer side effects
      than the current available agents. Increased awareness of co-morbid diseases in
      lupus is also leading to new approaches for the prevention of "disease damage" in
      lupus.

PMID- 16303107
TI  - Interferon pathway activation in systemic lupus erythematosus.
AB  - The recognition that a multitude of interferon (IFN)- inducible genes are
      coordinately expressed in peripheral blood cells of patients with systemic lupus
      erythematosus (SLE) has contributed to considerable interest in the IFN pathway
      as a therapeutic target in lupus. Together with data that have accumulated over
      the past four decades implicating IFN-alpha in SLE, the gene expression data have
      resulted in emergence of this cytokine pathway as a focal point for understanding
      mechanisms of autoimmunity and inflammation in systemic autoimmune diseases.
      Assays that measure IFN-inducible gene expression in patient cells and tissues
      and plasma assays that quantify IFN-alpha protein are providing tools for
      identification of patients with active disease and who may be responsive to
      inhibition of the innate immune system component of the altered immune response
      in SLE. In addition, investigations of the mechanisms of induction of IFN pathway
      activation are suggesting clues to the triggers of autoimmunity in SLE.

PMID- 16303108
TI  - New insights into the pathogenesis of systemic lupus erythematosus.
AB  - Although the etiology of systemic lupus erythematosus is unknown, recent studies
      have shed light on the pathogenetic pathways that lead to tissue damage. The
      immune system in systemic lupus erythematosus is characterized by a complex
      interplay between overactive B cells, abnormally activated T cells, and antigen
      presenting cells. This leads to the production of an array of inflammatory
      cytokines, diverse autoantibodies, and immune complexes that in turn activate
      effector cells and the complement system leading to the clinical manifestations
      of the disease.

PMID- 16303109
TI  - Revisiting the issue of malignancy risk in systemic lupus erythematosus.
AB  - Certain cancers occur more frequently in systemic lupus erythematosus (SLE) as
      compared with the general population, as recent data substantiates. The risk
      appears to be most heightened for lymphoma. Several pathogenic mechanisms may
      explain these observations, although little is definitively known. One particular
      concern relates to whether cancer risk in SLE is increased by medication
      exposures. Cooperative efforts to evaluate this have been undertaken by the
      Systemic Lupus International Collaborating Clinics and the Canadian Network for
      Improved Outcomes in Systemic Lupus research groups. This and other works in
      progress will, it is hoped, considerably advance the knowledge regarding the
      association between autoimmune diseases and malignancy.

PMID- 16303110
TI  - Bone health and systemic lupus erythematosus.
AB  - Osteoporosis is a potentially preventable condition frequently encountered in
      patients with systemic lupus erythematosus (SLE). Bone loss in SLE is likely a
      multi- factorial process involving traditional osteoporosis risk factors along
      with lupus-related factors. Recognizing potential contributors to bone loss in
      patients with SLE may allow earlier detection of osteoporosis, optimize bone
      health, and minimize future fracture risk. This paper discusses recent
      epidemiologic information related to osteoporosis and fractures in SLE, and
      highlights relevant developments regarding evaluation and treatment of patients
      at risk for bone loss.

PMID- 16303111
TI  - Osteoprotegerin as a potential therapy for osteoporosis.
AB  - The discovery and characterization of the RANKL/RANK/OPG signaling pathway and
      the identification of its role in the pathogenesis of bone loss have provided the
      rationale for the development of drugs with the ability to modulate RANK-induced
      osteoclastogenesis. In vivo studies have identified interfering with the
      RANKL/RANK interaction as a potential therapeutic target in the management of
      osteoporosis. Two agents capable of blocking the binding of RANKL to RANK have
      been so far tested in clinical studies--osteoprotegerin (Fc-OPG fusion molecule)
      and the RANKL-antibody (AMG 162). Both have been found to have profound
      inhibitory effects on bone resorption, with AMG 162 appearing to be overall
      superior to OPG. Data are still very scarce, however, and much remains to be
      uncovered before novel strategies capable of modulating the RANKL/OPG signaling
      pathway could be safely and effectively used in the management of osteoporosis.

PMID- 16303112
TI  - Detection of vertebral fractures.
AB  - Despite the importance of vertebral compression fractures, there is much that
      remains uncertain. There is no "gold standard" for the definition which has led
      to epidemiologic and study differences. Height loss is a way to suspect vertebral
      fractures but it has its own issues. There are multiple radiographic systems for
      defining vertebral fractures, both prevalent and incident; risk factors for
      prevalent fractures have already been delineated. Recent studies have elucidated
      the risk factors for incident vertebral fractures including age, low weight, late
      menarche, lower bone mineral density, history of vertebral and nonvertebral
      fractures, smoking, and use of a walking aid. Fan beam densitometers have had
      improving ability to image the spine, a procedure now known as vertebral fracture
      assessment (VFA). Recently (in the United States) a CPT code and reimbursement
      was established. Yet, many vertebral fractures go undiagnosed, diagnosed but
      unreported, or reported but not utilized in patient care. Because of this, the
      International Osteoporosis Foundation developed a Vertebral Fracture Initiative
      for radiologists and the International Society for Clinical Densitometry began a
      VFA course. Both teaching programs use the semi-quantitative assessment of Genant
      to aid the radiologists and clinicians in detecting vertebral fractures.

PMID- 16303113
TI  - Update on bone density testing.
AB  - Bone mineral density (BMD) testing is a noninvasive measurement to diagnose
      osteoporosis or low bone density, predict fracture risk, and monitor changes in
      bone density over time. The "gold-standard" technology for diagnosis and
      monitoring is dual-energy x-ray absorptiometry of the spine, hip, or forearm.
      Fracture risk can be predicted using a variety of technologies at many skeletal
      sites. BMD is usually reported as T-score, the standard deviation variance of the
      patient's BMD compared with a normal young-adult reference population. In
      untreated postmenopausal women, there is a strong correlation between T-score and
      fracture risk, with fracture risk increasing approximately two-fold for every
      standard deviation decrease in bone density. BMD in postmenopausal women is
      classified as normal, osteopenia, or osteoporosis according to criteria
      established by the World Health Organization. Standardized methodologies are
      being developed to establish intervention thresholds for pharmacologic therapy
      based on T-score combined with clinical risk factors for fracture.

PMID- 16303114
TI  - Anabolic therapy for osteoporosis: parathyroid hormone.
AB  - Recombinant human parathyroid hormone (PTH 1-34) is the only anabolic agent
      currently approved for the treatment of osteoporosis. The term anabolic is based
      on mechanism of action. PTH stimulates bone formation, in contrast to
      antiresorptive agents, which reduce bone resorption and formation. Recent
      investigations involving the PTH(1-34) and PTH(1-84) peptides, alone and in
      combination or sequential regimens with antiresorptive agents, have provided a
      greater understanding of the place of PTH in the armamentarium against
      osteoporosis. These studies indicate that adding a bisphosphonate to PTH in
      previously untreated individuals does not produce additional bone benefit;
      however, sequential use of PTH followed-up by an antiresorptive agent is highly
      effective at increasing BMD. Adding PTH after an antiresorptive agent also
      produces substantial bone density increments, though the magnitude of bone
      density increase may differ for different antiresorptive agents. PTH can repair
      underlying micro-architectural defects in bone, improve bone mass substantially,
      and perhaps change macro-architecture and geometry of bone. There are still many
      unanswered questions regarding PTH treatment of osteoporosis, including the
      optimal duration of treatment, optimal dosing regimen, mechanism of resistance to
      its effect after 18-24 months, and the effect of subsequent rechallenge.

PMID- 16303115
TI  - Combination therapy for osteoporosis: considerations and controversy.
AB  - Combination therapy, the simultaneous use of two pharmaceutical agents with the
      goal being reduction of fracture risk, is an area of substantial clinical
      interest. This paper summarizes the rationale, existing clinical trials data, and
      other considerations relevant to combination therapy for osteoporosis.
      Combinations of antiresorbers (eg, estrogen plus bisphosphonates) produce greater
      increases in bone mass than either treatment alone. Conversely, combining
      anabolic agents (parathyroid hormone) with bisphosphonates does not produce
      additive effects. None of the existing studies are large enough to determine
      whether combination treatment reduces fracture risk to a greater extent than use
      of a single agent. However, it is certain that combination treatment will
      increase cost and likely that it will increase side effects and reduce therapy
      adherence. Given the absence of demonstrated fracture reduction benefit,
      increased cost and likely increase in adverse events, combination therapy is not
      currently recommended.

PMID- 16303116
TI  - Mass transport in micellar surfactant solutions: 1. Relaxation of micelle
      concentration, aggregation number and polydispersity.
AB  - The surfactant transfer in micellar solutions includes transport of all types of
      aggregates and the exchange of monomers between them. Such processes are
      theoretically described by a system containing tens of kinetic equations, which
      is practically inapplicable. For this reason, one of the basic problems of
      micellar kinetics is to simplify the general set of equations without loosing the
      adequacy and correctness of the theoretical description. Here, we propose a
      model, which generalizes previous models in the following aspects. First, we do
      not use the simplifying assumption that the width of the micellar peak is
      constant under dynamic conditions. Second, we avoid the use of the quasi
      equilibrium approximation (local chemical equilibrium between micelles and
      monomers). Third, we reduce the problem to a self-consistent system of four
      nonlinear differential equations. Its solution gives the concentration of
      surfactant monomers, total micelle concentration, mean aggregation number, and
      halfwidth of the micellar peak as functions of the spatial coordinates and time.
      Further, we check the predictions of the model for the case of spatially uniform
      bulk perturbations (such as jumps in temperature, pressure or concentration). The
      theoretical analysis implies that the relaxations of the three basic parameters
      (micelle concentration, mean aggregation number, and polydispersity) are
      characterized by three different characteristic relaxation times. Two of them
      coincide with the slow and fast micellar relaxation times, which are known in the
      literature. The third time characterizes the relaxation of the width of the
      micellar peak (i.e. of the micelle polydispersity). It is intermediate between
      the slow and fast relaxation times, in the case of not-too-low micellar
      concentrations. For low micelle concentrations, the third characteristic time is
      close to the fast relaxation time. Procedure for obtaining the exact numerical
      solution of the problem is formulated. In addition, asymptotic analytical
      expressions are derived, which compare very well with the exact numerical
      solution. In the second part of this study, the obtained set of equations is
      applied for theoretical modeling of surfactant adsorption from micellar solutions
      under various dynamic conditions, corresponding to specific experimental methods.

PMID- 16303117
TI  - Expression of gamma-glutamyltransferase in cancer cells and its significance in
      drug resistance.
AB  - The expression of gamma-glutamyltransferase (GGT), a cell surface enzyme involved
      in cellular glutathione homeostasis, is often significantly increased in human
      tumors, and its role in tumor progression, invasion and drug resistance has been
      repeatedly suggested. As GGT participates in the metabolism of cellular
      glutathione, its activity has been mostly regarded as a factor in reconsitution
      of cellular antioxidant/antitoxic defences. On this basis, an involvement of GGT
      expression in resistance of cancer cells to cytotoxic drugs (in particular,
      cisplatin and other electrophilic agents) has been envisaged. Mechanistic aspects
      of GGT involvement in antitumor pharmacology deserve however further
      investigations. Recent evidence points to a more complex role of GGT in
      modulation of redox equilibria, with effects acting both intracellularly and in
      the extracellular microenvironment. Indications exist that the protective effects
      of GGT may be independent of intracellular glutathione, and derive rather from
      processes taking place at extracellular level and involving reactions of
      electrophilic drugs with thiol metabolites originating from GGT-mediated cleavage
      of extracellular glutathione. Although expression of GGT cannot be regarded as a
      general mechanism of resistance, the involvement of this enzyme in modulation of
      redox metabolism is expected to have impact in cellular response to several
      cytotoxic agents. The present commentary is a survey of data concerning the role
      of GGT in tumor cell biology and the mechanisms of its potential involvement in
      tumor drug resistance.

PMID- 16303118
TI  - Identification of novel subtype selective RAR agonists.
AB  - Drugs targeting retinoid receptors have been developed to treat a variety of
      therapeutic indications, but their success has been limited in part due to lack
      of selectivity. A novel functional cell-based assay R-SATtrade mark was employed
      to screen a small molecule chemical library and identify a variety of novel RAR
      agonists with various subtype selectivities, including RARbeta/gamma and RARgamma
      selective agonists. A novel class of synthetic compounds that distinguishes
      between the different RARbeta isoforms is described. This pharmacophore displays
      anti-proliferative activity and induces differentiation in a neuronal cell line,
      consistent with a classical retinoid mechanism of action while providing unique
      subtype selectivity. These novel subtype selective RAR agonists could serve as
      powerful tools to probe into subtype and isoform-specific retinoid function.

PMID- 16303119
TI  - Cloning and characterization of Thermotoga maritima beta-glucuronidase.
AB  - The putative beta-glucuronidase from Thermotoga maritima, comprising 563 amino
      acid residues conjugated with a Hisx6 tag, was cloned and expressed in
      Escherichia coli. The enzyme has a moderately broad specificity, hydrolysing a
      range of p-nitrophenyl glycoside substrates, but has greatest activity on p
      nitrophenyl beta-D-glucosiduronic acid (kcat=68 s(-1), kcat/K(M)= 4.5x10(5) M(-1)
      s(-1)). The enzyme also shows a relatively broad pH-dependence with activity from
      pH4.5 to 7.5 and a maximum at pH6.5. As expected the enzyme is stable towards
      heat denaturation, with a half life of 3h at 85 degrees C, in contrast to the
      mesophilic E. coli enzyme, which has a half life of 2.6h at 50 degrees C. The
      identity of the catalytic nucleophile was confirmed as Glu476 within the sequence
      VTEFGAD by trapping the glycosyl-enzyme intermediate using the mechanism-based
      inactivator, 2-deoxy-2-fluoro-beta-D-glucosyluronic acid fluoride and identifying
      the labeled peptide in peptic digests by HPLC-MS/MS methodologies. Consistent
      with this, the Glu476Ala mutant was shown to be hydrolytically inactive. The
      acid/base catalyst was confirmed as Glu383 by generation and kinetic analysis of
      enzyme mutants modified at that position, Glu383Ala and Glu383Gln. The
      demonstration of activity rescue by azide is consistent with the proposed role
      for this residue. This enzyme therefore appears suitable for use in enzymatic
      oligosaccharide synthesis in either the transglycosylation mode or by use of
      glycosynthase and thioglycoligase approaches.

PMID- 16303120
TI  - Junctional and extrajunctional acetylcholinesterase in skeletal muscle fibers.
AB  - The asymmetric A12 acetylcholinesterase (AChE) molecular form, consisting of
      three tetrameric catalytic oligomers and three non-catalytic subunits of collagen
      Q (ColQ), is the functional AChE form in the neuromuscular junction. Its
      extremely high concentration and sharp localization in the junction is mostly due
      to the binding of this AChE form to perlecan in the synaptic basal lamina. In the
      rat neuromuscular junctions, about two-thirds of AChE molecules appear to be
      bound by ionic interactions involving calcium and the rest is probably bound
      covalently. In immature rat muscles, the A12 AChE forms are expressed also
      extrajunctionally. During the early post-natal period, this expression is
      completely suppressed in rat fast muscles, whereas it extends into adulthood in
      the slow soleus muscles because of the differences in the extrajunctional
      expression of ColQ between fast and slow muscles. The level of the A12 molecular
      forms of AChE in the extrajunctional muscle regions is regulated by the motor
      nerve, probably via the pattern of muscle fibre activations triggered by the
      nerve. The pattern of muscle activations also regulates the extrajunctional
      expression of the catalytic subunits of AChE: phasic, infrequent, high frequency
      activations enhance expression, whereas prolonged tonic low-frequency activations
      tend to decrease it. Calcineurin signalling pathway seems to be involved.

PMID- 16303121
TI  - A long ripple phase in DLPC-decylglucoside mixture evidenced by synchrotron SAXS
      coupled to DSC.
AB  - For the first time, the secondary ripple phase in a system containing dilauroyl
      phosphatidylcholine (DLPC) is observed by small-angle X-ray diffraction (SAXS).
      The SAXS profile exhibits many well-resolved peaks. The fast formation of this
      phase upon cooling from the liquid crystalline lamellar phase L(alpha) is induced
      by addition of C10G with molar ratio 0.17< or = R = [C10G]/[DLPC]< or = 0.49. For
      R < 0.17, the primary P(beta') ripple phase is observed. In contrast to the
      P(beta') phase, which shows a sawtooth shape, the secondary ripple structure is
      thought to be symmetric. The ripple length (190 angstroms) and the bilayer
      spacing (74 angstroms) are larger than in the primary ripple phase. Lattice
      parameters of the new long ripple phase, which are quite insensitive to
      temperature, vary slightly linearly with R. In this study, structural and
      thermodynamic changes within the samples were followed as a function of
      temperature by time-resolved X-ray diffraction coupled to DSC.

PMID- 16303122
TI  - The relationship between ACE insertion/deletion polymorphism and coronary artery
      disease with or without myocardial infarction.
AB  - OBJECTIVES: Presence of the D allele or homozygosity for the deletion (D) allele
      of the angiotensicen-converting enzyme (ACE) insertion/deletion (I/D)
      polymorphism has been discussed as potent risk factor for coronary artery disease
      (CAD) and myocardial infarction (MI). The D allele is associated with higher
      levels of circulating ACE and therefore may predispose one to cardiovascular
      damage. DESIGN AND METHODS: The study presented here was performed to investigate
      the association between the ACE genotype and ACE levels. The study group was
      comprised of 118 angiographically verified CAD patients. 65 patients were MI (+)
      and 53 patients were MI (-) in this group. A total of 70 healthy individuals were
      taken as controls. Genomic DNA of 188 subjects was extracted from whole blood.
      The polymerase chain reaction was used for ACE genotyping, and ACE levels were
      measured by ELISA. RESULTS: The D allele was found to be significantly more
      frequent in patients with MI (+) compared with controls (P = 0.024). ACE levels
      were significantly higher in both MI (-) and MI (+) groups with CAD patients than
      in controls (P < 0.005). Plasma ACE level was higher in all three groups in the
      DD genotype compared to II genotype. In groups I and III, this was statistically
      significant (P < 0.0001, P < 0.01). CONCLUSIONS: It was shown that the I/D
      polymorphism in the gene for ACE is a genetic risk factor for CAD patients who
      have a history of MI. ACE insertion/deletion gene polymorphism is also associated
      with plasma ACE levels in CAD patients with a history of MI.

PMID- 16303123
TI  - Fetal lung maturity.
AB  - Respiratory distress syndrome of the newborn infant caused by immaturity of the
      fetal lung continues to be a clinical problem. Measurement of pulmonary
      surfactant production is the most effective way to evaluate pulmonary maturity.
      Since the first fetal lung maturity test was described more than two decades ago,
      advances in methodology have produced diagnostically sensitive tests that are
      both rapid and precise. Unfortunately, currently available tests continue to
      demonstrate low diagnostic specificity and remain poor predictors of fetal lung
      immaturity. We review the background, methodology, pre-analytical and analytical
      concerns, and clinical performance of various fetal lung maturity assays, and
      discuss the appropriate use and interpretation of these tests.

PMID- 16303124
TI  - Ionotropic glutamatergic neurotransmission in the ventral tegmental area
      modulates DeltaFosB expression in the nucleus accumbens and abstinence syndrome
      in morphine withdrawal rats.
AB  - The present study sought to assess whether the blockade of ionotropic glutamate
      receptors in the ventral tegmental area could modulate morphine withdrawal in
      morphine-dependent rats and the expression of stable DeltaFosB isoforms in the
      nucleus accumbens during morphine withdrawal. Rats were injected (i.p.) with
      increasing doses of morphine for 1 week to develop physical dependence, and
      withdrawal was then precipitated by one injection of naloxone (2 mg/kg, i.p.).
      Abstinence signs such as jumping, wet-dog shake, writhing posture, weight loss,
      and Gellert-Holtzman scale score were recorded to evaluate naloxone-induced
      morphine withdrawal. Two ionotropic glutamate receptor antagonists, dizocilpine
      (MK-801) and 6, 7-dinitroquinnoxaline-2, 3-dione (DNQX), were microinjected
      unilaterally into the ventral tegmental area 30 min before naloxone
      precipitation. A second injection of naloxone (2 mg/kg i.p.) was given 1 h after
      the first naloxone injection to sustain a maximal level of withdrawal so that the
      expression of stable DeltaFosB isoforms in the nucleus accumbens could be
      measured. This would enable determination of the correlation between the MK-801
      or DNQX-induced decrease in somatic withdrawal signs and the change in neuronal
      activity in the nucleus accumbens. The results showed that both MK-801 and DNQX
      significantly alleviated all symptoms of morphine withdrawal except for weight
      loss and reduced the expression of stable DeltaFosB isoforms within the nucleus
      accumbens. These data suggest that ionotropic glutamatergic neurotransmission in
      the ventral tegmental area regulates the levels of stable DeltaFosB isoforms in
      the nucleus accumbens, which play a very important role in modulating opiate
      withdrawal.

PMID- 16303125
TI  - Pericytes and vascular stability.
AB  - Newly formed endothelial tubes are initially unstable and subsequently become
      stabilized through the formation of a perivascular matrix and the association
      with pericytes. The presence of pericyte per se is not sufficient for vascular
      stability. Instead, specific qualities of the cells are required that seem to
      correlate with marker expression and the nature of the endothelial-pericyte
      contacts. Most likely, specific intercellular signals are required as mediators
      of endothelial and pericyte cell function and vascular stability. Several ligand
      receptor systems have been implicated in endothelial-pericyte interactions. Here,
      we discuss the role of some of these signaling systems in the regulation of
      vascular stability.

PMID- 16303126
TI  - Lenticular chaperones suppress the aggregation of the cataract-causing mutant T5P
      gamma C-crystallin.
AB  - The T5P mutation in human gamma C-crystallin produces a lens cataract. Here, we
      have investigated the effects of the T5P mutation upon the aggregation of gamma C
      crystallin in vitro and in transfected cells. By sedimentation assay and sucrose
      gradient centrifugation, the mutation significantly increased the aggregation of
      the protein and reduced dramatically its solubility in vitro. Similar effects
      were seen when T5P gamma C-crystallin was transfected into tissue culture cells,
      resulting in the formation of cytoplasmic aggregates of T5P gamma C-crystallin.
      Interestingly, the major lenticular protein chaperones, alpha A- and alpha B
      crystallin, increased the solubility of the T5P gamma C-crystallin both in vitro
      and in transfected cells. More importantly, the size of the T5P gamma C
      crystallin aggregates were also significantly reduced in the presence of the
      lenticular chaperones. These data therefore suggest a dual role for these
      chaperones in maintaining transparency in the lens. The first is that these
      protein chaperones increase the proportion of the soluble T5P gamma C-crystallin
      and the second is that they also reduce light scatter by reducing the aggregate
      size of T5P gamma C-crystallin. Both activities could modify the cataract
      phenotype and help explain the observed variability reported for identical gamma
      crystallin mutations, which identify cataract as a polygenic disease.

PMID- 16303127
TI  - Stromal haze, myofibroblasts, and surface irregularity after PRK.
AB  - The aim of this study was to investigate the relationship between the level of
      stromal surface irregularity after photorefractive keratectomy (PRK) and
      myofibroblast generation along with the development of corneal haze. Variable
      levels of stromal surface irregularity were generated in rabbit corneas by
      positioning a fine mesh screen in the path of excimer laser during ablation for a
      variable percentage of the terminal pulses of the treatment for myopia that does
      not otherwise generate significant opacity. Ninety-six rabbits were divided into
      eight groups: [see table in text]. Slit lamp analysis and haze grading were
      performed in all groups. Rabbits were sacrificed at 4 hr or 4 weeks after surgery
      and histochemical analysis was performed on corneas for apoptosis (TUNEL assay),
      myofibroblast marker alpha-smooth muscle actin (SMA), and integrin alpha4 to
      delineate the epithelial basement membrane. Slit-lamp grading revealed severe
      haze formation in corneas in groups IV and VI, with significantly less haze in
      groups II, III, and VII and insignificant haze compared with the unwounded
      control in groups I and V. Analysis of SMA staining at 4 weeks after surgery, the
      approximate peak of haze formation in rabbits, revealed low myofibroblast
      formation in group I (1.2+/-0.2 cells/400x field) and group V (1.8+/-0.4), with
      significantly more in groups II (3.5+/-1.8), III (6.8+/-1.6), VII (7.9+/-3.8), IV
      (12.4+/-4.2) and VI (14.6+/-5.1). The screened groups were significantly
      different from each other (p < 0.05), with myofibroblast generation increasing
      with higher surface irregularity in the -4.5 diopter PRK groups. The -9.0 diopter
      PRK group VI had significantly more myofibroblast generation than the -9.0
      diopter PRK with PTK-smoothing group VII (p < 0.01). Areas of basement membrane
      disruption were demonstrated by staining corneas for integrin alpha4 and were
      prominent in corneas with grade I or higher haze. SMA-positive myofibroblasts
      tended to be present sub-adjacent to basement membrane defects. Late apoptosis
      was detected at 1 month after surgery within clusters of myofibroblasts in the
      sub-epithelial stroma. In conclusion, these results demonstrated a relationship
      between the level of corneal haze formation after PRK and the level of stromal
      surface irregularity. PTK-smoothing with methylcellulose was an effective method
      to reduce stromal surface irregularity and decreased both haze and associated
      myofibroblast density. We hypothesize that stromal surface irregularity after PRK
      for high myopia results in defective basement membrane regeneration and increased
      epithelium-derived TGFbeta signalling to the stroma that increases myofibroblast
      generation. Late apoptosis appears to have a role in the disappearance of
      myofibroblasts and haze over time.

PMID- 16303128
TI  - Neuroanatomical approaches of the tectum-reticular pathways and
      immunohistochemical evidence for serotonin-positive perikarya on neuronal
      substrates of the superior colliculus and periaqueductal gray matter involved in
      the elaboration of the defensive behavior and fear-induced analgesia.
AB  - Deep layers of the superior colliculus, the dorsal periaqueductal gray matter and
      the inferior colliculus are midbrain structures involved in the generation of
      defensive behavior and fear-induced anti-nociception. Local injections of the
      GABA(A) antagonist bicuculline into these structures have been used to produce
      this defense reaction. Serotonin is thought to be the main neurotransmitter to
      modulate such defense reaction in mammals. This study is the first attempt to
      employ immunohistochemical techniques to locate serotonergic cells in the same
      midbrain sites from where defense reaction is evoked by chemical stimulation with
      bicuculline. The blockade of GABA(A) receptors in the neural substrates of the
      dorsal mesencephalon was followed by vigorous defensive reactions and increased
      nociceptive thresholds. Light microscopy immunocytochemistry with streptavidin
      method was used for the localization of the putative cells of defensive behavior
      with antibodies to serotonin in the rat's midbrain. Neurons positive to serotonin
      were found in the midbrain sites where defensive reactions were evoked by
      microinjection of bicuculline. Serotonin was localized to somata and projections
      of the neural networks of the mesencephalic tectum. Immunohistochemical studies
      showed that the sites in which neuronal perikarya positive to serotonin were
      identified in intermediate and deep layers of the superior colliculus, and in the
      dorsal and ventral columns of the periaqueductal gray matter are the same which
      were activated during the generation of defense behaviors, such as alertness,
      freezing, and escape reactions, induced by bicuculline. These findings support
      the contention that serotonin and GABAergic neurons may act in concert in the
      modulation of defense reaction in the midbrain tectum. Our neuroanatomical
      findings indicate a direct neural pathway connecting the dorsal midbrain and
      monoaminergic nuclei of the descending pain inhibitory system, with profuse
      synaptic terminals mainly in the pontine reticular formation, gigantocellularis
      nucleus, and nucleus raphe magnus. The midbrain tectum-gigantocellularis complex
      and midbrain tectum-nucleus raphe magnus neural pathways may provide an
      alternative output allowing the organization of the fear-induced anti-nociception
      by mesencephalic networks.

PMID- 16303129
TI  - Conventional and color Doppler sonography in preoperative assessment of ovarian
      tumors.
AB  - OBJECTIVE: To study the vascular patterns of ovarian tumors by color Doppler
      imaging (CDI) and compare the findings of conventional sonographic studies and
      CDI with histopathologic findings for the same tumors. METHODS: Fifty nonpregnant
      women scheduled for elective surgery for ovarian tumors were examined by
      sonographic scanning and CDI by the same physician. Sonographic morphology scores
      [SMSs] were used, and the pulsatility index (PI) and resistance index (RI) were
      calculated after locating vessels in and around the tumors by CDI. RESULTS: It
      was possible to obtain CDI results in 26 of the 50 women. The sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      were 100%, 71.43%, 73.33%, and 100%, respectively, for SMS. With CDI, the
      sensitivity, specificity, PPV, and NPV were 100%, 85.72%, 95%, and 100% for PI
      and 100%, 71.43%, 90.48%, and 100% for RI. RI sensitivity and specificity were
      identical to those of SMS, i.e., 100% and 71.43%, respectively, but PI
      specificity was better (85.72%). CONCLUSION: In this study, CDI was definitely
      better than SMS when color flow could be obtained through the tumors. The overall
      efficiency in diagnosing the nature of tumors is very high if SMS and CDI are
      both used in patients having ovarian tumors.

PMID- 16303130
TI  - Multiple headspace single-drop microextraction-a new technique for quantitative
      determination of styrene in polystyrene.
AB  - Single-drop microextraction (SDME), an emerging miniaturised extraction
      technique, was for the first time combined with multiple headspace extraction
      (MHE) to enable the quantitative determination of volatiles in solid matrixes by
      SDME technique. The concept of multiple headspace single-drop microextraction
      (MHS-SDME) was then applied for quantitative determination of styrene in
      polystyrene (PS) samples. Good linearity for the multiple headspace extraction
      was obtained when the migration of styrene was facilitated by grinding the
      samples and incubating them for 1 h at 150 degrees C prior the first extraction.
      Two microlitres of butyl acetate was used as the single-drop microextraction
      solvent and the extraction time was 5 min per cycle. The relative standard
      deviation (RSD) for single-drop microextraction of styrene standard at n=6 was
      7.6%. Linearity was shown for styrene concentrations between 0.005 and 0.75
      microg/ml (R2=0.999). This corresponds to total amount of styrene between 0.1 and
      15 microg. The limit of quantitation for styrene standard at S/N 10 was 0.005
      microg/ml. The developed method was validated against and showed good agreement
      with an earlier reported dissolution-precipitation method.

PMID- 16303131
TI  - Electroosmotic flow in poly(dimethylsiloxane) microchannels.
AB  - This paper reports on the study of electroosmotic flow (EOF) in
      poly(dimethylsiloxane) (PDMS) microchannels on the basis of indirect amperometric
      detection method. Gradual increase of EOF rate in freshly prepared PDMS
      microchannels was observed with the running buffer of phosphate buffer solution
      (PBS). With the same concentration (10 mM) of PBS containing different cations
      and the same pH value (7.0) and, the time of the stable EOF in PDMS microchannels
      under the applied separation voltage of 1000 V was 49.8 s (Li+ -PBS), 57.1 s (Na+
      -PBS), 91 s (K+ -PBS), respectively. Meanwhile, the different adsorption of
      cations (Li+, Na+ and K+) on hydrophobic PDMS wall was observed through their
      separation in PDMS microchannels. Such experimental results demonstrated that the
      EOF in PDMS microchannels came from the cations and anions adsorbed on PDMS wall.
      This study would not only help us understand the surface state of PDMS, but also
      provide a useful guidance for establishing the effective surface modification
      methods in PDMS microchip CE.

PMID- 16303132
TI  - Incidence and transmission of a granulovirus in a large codling moth [Cydia
      pomonella L. (Lepidoptera: Tortricidae)] rearing facility.
AB  - Incidences of potential per os Cydia pomonella granulovirus (CpGV) transmission
      within a large codling moth colony were identified. CpGV was detected in the
      water which is used to wash egg sheets. When pre-neonates were extracted from
      eggs prior to emergence and tested for the presence of CpGV, 40% were found to
      carry amounts of CpGV detectable by a polymerase chain reaction (PCR) assay,
      suggesting possible transovarial transmission of the virus. Although symptoms
      typical of virus infection and larval death were found infrequently within
      communal rearing trays, the frequency with which CpGV DNA was detected by PCR
      assays increased from a mean of 31% of 10-day-old larvae to 94% of 25-day-old
      larvae. CpGV in codling moth cadavers remained virulent after being held at 60
      degrees C for 3 days under conditions similar to the treatment of spent diet at
      the rearing facility before its disposal. PCR tests of surface samples taken from
      air filters and rearing rooms of the rearing facility were found to contain CpGV.
      Bioassays of surface samples from the diet trash bin and a filter through which
      outside air is passed before entering the rearing chambers resulted in
      significant codling moth neonate mortality. The virulence of CpGV in dust from
      the spent diet and the original inadvertent positioning of the diet trash bin
      directly below one of the air intake ducts are suggested as a possible additional
      source of CpGV contamination within the facility.

PMID- 16303133
TI  - Determinants of product topology in a hybrid Cre-Tn3 resolvase site-specific
      recombination system.
AB  - Many natural DNA site-specific recombination systems achieve directionality
      and/or selectivity by making recombinants with a specific DNA topology. This
      property requires that the DNA architecture of the synapse and the mechanism of
      strand exchange are both under strict control. Previously we reported that Tn3
      resolvase-mediated synapsis of the accessory binding sites from the Tn3
      recombination site res can impose topological selectivity on Cre/loxP
      recombination. Here, we show that the topology of these reactions is profoundly
      affected by subtle changes in the hybrid recombination site les. Reversing the
      orientation of loxP relative to the res accessory sequence, or adding 4 bp to the
      DNA between loxP and the accessory sequence, can switch between two-noded and
      four-noded catenane products. By analysing Holliday junction intermediates, we
      show that the innate bias in the order of strand exchanges at loxP is maintained
      despite the changes in topology. We conclude that a specific synaptic structure
      formed by resolvase and the res accessory sequences permits Cre to align the
      adjoining loxP sites in several distinct ways, and that resolvase-mediated
      intertwining of the accessory sequences may be less than has been assumed
      previously.

PMID- 16303134
TI  - Environmental control of the in vivo oligomerization of nucleoid protein H-NS.
AB  - The nucleoid-associated transcriptional repressor H-NS forms both dimers and
      tetramers in vivo. Two types of two-hybrid systems, one capable of detecting
      protein dimerization and the other protein tetramerization, have been used to
      determine whether environmental changes could affect the oligomerization capacity
      of this protein in the cell. Increasing the temperature from 37 degrees C to 48
      degrees C and changing the pH between 4.0 and 9.0 did not influence either
      dimerization or tetramerization, whereas lowering the temperature below 25
      degrees C and increasing osmolarity were found to reduce the formation of H-NS
      tetramers, which are the active form of this protein, without affecting
      dimerization. These findings provide a rationale to explain the induction of H-NS
      expression during cold-shock, suggest a mechanism contributing to derepressing
      osmotic-shock genes transcriptionally regulated by H-NS and indicate that changes
      of the oligomerization properties of H-NS do not play a role in the H-NS and
      temperature-dependent control of virulence gene expression.

PMID- 16303135
TI  - Analysis of interactions between mismatch repair initiation factors and the
      replication processivity factor PCNA.
AB  - In eukaryotes, the DNA replication factor PCNA is loaded onto primer-template
      junctions to act as a processivity factor for DNA polymerases. Genetic and
      biochemical studies suggest that PCNA also functions in early steps in mismatch
      repair (MMR) to facilitate the repair of misincorporation errors generated during
      DNA replication. These studies have shown that PCNA interacts directly with
      several MMR components, including MSH3, MSH6, MLH1, and EXO1. At present, little
      is known about how these interactions contribute to the mismatch repair
      mechanism. The interaction between MLH1 and PCNA is of particular interest
      because MLH1-PMS1 is thought to act as a matchmaker to signal mismatch
      recognition to downstream repair events; in addition, PCNA has been hypothesized
      to act in strand discrimination steps in MMR. Here, we utilized both genetic and
      surface plasmon resonance techniques to characterize the MLH1-PMS1-PCNA
      interaction. These analyses enabled us to determine the stability of the complex
      (K(D) = 300 nM) and to identify residues (572-579) in MLH1 and PCNA (126,128)
      that appear important to maintain this stability. We favor a model in which PCNA
      acts as a scaffold for consecutive protein-protein interactions that allow for
      the coordination of MMR steps.

PMID- 16303136
TI  - Destabilization of human IAPP amyloid fibrils by proline mutations outside of the
      putative amyloidogenic domain: is there a critical amyloidogenic domain in human
      IAPP?
AB  - Islet amyloid polypeptide (IAPP; amylin) is responsible for amyloid formation in
      type-2 diabetes. Not all organisms form islet amyloid, and amyloid formation
      correlates strongly with variations in primary sequence. Studies of human and
      rodent IAPP have pointed to the amino acid residues 20-29 region as the important
      amyloid-modulating sequence. The rat 20-29 sequence contains three proline
      residues and does not form amyloid, while the human sequence contains no proline
      and readily forms amyloid. This has led to the view that the 20-29 region
      constitutes a critical amyloidogenic domain that dictates the properties of the
      entire sequence. The different behavior of human and rat IAPP could be due to
      differences in the 20-29 region or due simply to the fact that multiple proline
      residues destabilize amyloid fibrils. We tested how critical the 20-29 region is
      by studying a variant identical with the human peptide in this segment but with
      three proline residues outside this region. We designed a variant of the
      amyloidogenic 8-37 region of human IAPP (hIAPP(8-37) 3xP) with proline
      substitutions at positions 17, 19 and 30. Compared to the wild-type, the 3xP
      variant was much easier to synthesize and had dramatically greater solubility.
      Fourier transform infra red spectroscopy, transmission electron microscopy, Congo
      red staining and thioflavin-T binding indicate that this variant has a reduced
      tendency to form beta-sheet structure and forms deposits with much less
      structural order than the wild-type. Far-UV CD studies show that the small amount
      of beta-sheet structure developed by hIAPP(8-37) 3xP after long periods of
      incubation dissociates readily into random-coil structure upon dilution into Tris
      buffer. The observation that proline substitutions outside the putative core
      domain effectively abolish amyloid formation indicates that models of IAPP
      aggregation must consider contributions from other regions.

PMID- 16303137
TI  - Secondary structure of alpha-synuclein oligomers: characterization by raman and
      atomic force microscopy.
AB  - Formation of alpha-synuclein aggregates is proposed to be a crucial event in the
      pathogenesis of Parkinson's disease. Large soluble oligomeric species are
      observed as probable intermediates during fibril formation and these, or related
      aggregates, may constitute the toxic element that triggers neurodegeneration.
      Unfortunately, there is a paucity of information regarding the structure and
      composition of these oligomers. Here, the morphology and the conformational
      characteristics of the oligomers and filaments are investigated by a combined
      atomic force microscopy (AFM) and Raman microscopic approach on a common mica
      surface. AFM showed that in vitro early stage oligomers were globular with
      variable heights, while prolonged incubation caused the oligomers to become
      elongated as protofilaments. The height of the subsequently formed alpha
      synuclein filaments was similar to that of the protofilaments. Analysis of the
      Raman amide I band profiles of the different alpha-synuclein oligomers
      establishes that the spheroidal oligomers contain a significant amount of alpha
      helical secondary structure (47%), which decreases to about 37% in
      protofilaments. At the same time, when protofilaments form, beta-sheet structure
      increases to about 54% from the approximately 29% observed in spheroidal
      oligomers. Upon filament formation, the major conformation is beta-sheet (66%),
      confirmed by narrowing of the amide I band and the profile maximum shifting to
      1667 cm(-1). The accumulation of spheroidal oligomers of increasing size but
      unchanged vibrational spectra during the fibrillization process suggests that a
      cooperative conformational change may contribute to the kinetic control of
      fibrillization.

PMID- 16303138
TI  - Concordant exploration of the kinetics of RNA folding from global and local
      perspectives.
AB  - Time-resolved small-angle X-ray scattering (SAXS) with millisecond time
      resolution reveals two discrete phases of global compaction upon Mg2+-mediated
      folding of the Tetrahymena thermophila ribozyme. Electrostatic relaxation of the
      RNA occurs rapidly and dominates the first phase of compaction during which the
      observed radius of gyration (R(g)) decreases from 75 angstroms to 55 angstroms. A
      further decrease in R(g) to 45 angstroms occurs in a well-defined second phase.
      An analysis of mutant ribozymes shows that the latter phase depends upon the
      formation of long-range tertiary contacts within the P4-P6 domain of the
      ribozyme; disruption of the three remaining long-range contacts linking the
      peripheral helices has no effect on the 55-45 angstroms compaction transition. A
      better understanding of the role of specific tertiary contacts in compaction was
      obtained by concordant time-resolved hydroxyl radical (OH) analyses that report
      local changes in the solvent accessibility of the RNA backbone. Comparison of the
      global and local measures of folding shows that formation of a subset of native
      tertiary contacts (i.e. those defining the ribozyme core) can occur within a
      highly compact ensemble whose R(g) is close to that of the fully folded ribozyme.
      Analyses of additional ribozyme mutants and reaction conditions establish the
      generality of the rapid formation of a partially collapsed state with little to
      no detectable tertiary structure. These studies directly link global RNA
      compaction with formation of tertiary structure as the molecule acquires its
      biologically active structure, and underscore the strong dependence on salt of
      both local and global measures of folding kinetics.

PMID- 16303139
TI  - Recidivism study of New Mexico's convicted DWI offenders 2000-2003.

PMID- 16303140
TI  - Suicides and other fatalities from train-person collisions on Swedish railroads:
      a descriptive epidemiologic analysis as a basis for systems-oriented prevention.
AB  - PROBLEM: Suicide is a dominating, although hidden, safety problem on Swedish
      railroads. The aim of this paper is to describe the epidemiology of fatal train
      person collisions as a basis for systems-oriented prevention. METHOD: Data on
      collision circumstances were collected from narrative reports at the Swedish
      National Rail Administration. RESULTS: The events were evenly distributed by
      months and weekdays, however, most suicides occur during the day while
      unintentional events usually occur at night. Most train-person collisions
      happened in densely populated areas, and 75% of the suicide victims were waiting
      on the track before the collision. Significance test between types of injury
      event (suicide, accident, or unknown intent) showed small or no differences.
      CONCLUSION: Traditional approaches to accident prevention by systems modification
      seem largely applicable to combat railroad suicide as well. IMPACT ON INDUSTRY:
      Our findings show promising preventive potentials.

PMID- 16303141
TI  - Autoantibodies against HSP70 family proteins were detected in the cerebrospinal
      fluid from patients with multiple sclerosis.
AB  - We evaluated the specific IgG antibodies against heat shock proteins (HSPs) in
      cerebrospinal fluids (CSF) from patients with multiple sclerosis (MS). ELISA was
      employed to examine IgG antibodies against ten HSPs (HSP27, alphaA and alphaB
      crystallins, HSP60, CCT, Mycobacterium bovis HSP65, Escherichia coli GroEL,
      HSP70, HSC70 and HSP90) in CSF from 30 patients with MS, and 25 patients with
      motor neuron diseases (MND). Significantly higher antibody titers against HSP70
      and HSC70 proteins were found in CSF obtained from patients with MS as compared
      with MND independent of CSF total protein, IgG concentrations and IgG indices,
      respectively. The antibody titers against HSP70 were indicated to be
      significantly higher in the progressive cases than in cases of remission. The
      results suggest that IgG antibodies against specific types of HSPs especially
      HSP70 family proteins (HSP70 and HSC70) in CSF may play an important role in the
      pathophysiology of MS through the modification of immune response and
      cytoprotective functions of molecular chaperons.

PMID- 16303142
TI  - A mathematical analysis of the action potential plateau duration of a human
      ventricular myocyte.
AB  - The plateau phase of a human ventricular myocyte is analysed. The plateau
      duration is a function of the time required for a myocyte's transmembrane voltage
      to decrease by a certain voltage, DeltaV. The timing of the plateau is shown to
      be controlled by two slowly changing gate variables, the inactivation gate that
      controls the inward/depolarizing L-type calcium current and the inactivation gate
      that controls the outward/repolarizing slow rectifier potassium current. The
      amount of current controlled by these variables is a function of the net
      conductivity of the corresponding sodium and potassium channels. An equation is
      derived that relates action potential duration to these net conductivities and
      the time dependence of the slowly moving variables. This equation is used to
      estimate plateau duration for a given value of DeltaV. The initial conditions of
      the slowly moving inactivation variables are shown to affect plateau duration.
      These initial conditions depend on the amount of time that has elapsed between a
      previous repolarization and a current depolarization (diastolic interval). The
      analysis thus helps to quantify the characteristics of action potential duration
      restitution.

PMID- 16303144
TI  - Caffeic acid phenethyl ester ameliorates cerebral infarction in rats subjected to
      focal cerebral ischemia.
AB  - The effects of caffeic acid phenethyl ester (CAPE), an antioxidant derived from
      propolis, on the infarct volume elicited by focal cerebral ischemia were studied
      on Long-Evans rats. Cerebral infarction was induced by microsurgical procedures
      with ligation of the right middle cerebral artery (MCA) and clipping of bilateral
      common carotid arteries (CCA) for 60 min. The rats were sacrificed 24 h later and
      serial brain slices of 2 mm thickness were taken and stained for the measurement
      of infarct area. CAPE was administered intravenously 15 min before MCA occlusion.
      Pretreatment of CAPE (0.1, 1 and 10 microg/kg) significantly reduced the total
      infarct volume from 169.6 +/- 14.5 mm3 (control) to 61.0 +/- 24.1 mm3 (0.1
      microg/kg CAPE), 47.4 +/- 9.1 mm3 (1 microg/kg CAPE), and 42.4 +/- 8.7 mm3 (10
      microg/kg CAPE), respectively. Plasma nitric oxide (NO) content was significantly
      increased in rats subjected to focal cerebral ischemia. It is concluded that CAPE
      possesses neuroprotective properties in focal cerebral ischemia injury in rats
      possibly through its antioxidant effect and/or via the upregulation of NO
      production.

PMID- 16303143
TI  - Immunosuppressant FK506 inhibits matrix metalloproteinase-9 induction in TNF
      alpha-stimulated human hepatic stellate cells.
AB  - Activated hepatic stellate cells (HSCs) play a key role in the pathogenesis of
      hepatic inflammation and fibrosis through the production of matrix
      metalloproteinases (MMPs). Cytokines and growth factors are thought to activate
      HSCs. TNF-alpha has pleiotropic functions in hepatitis, but its role in liver
      fibrosis remains elusive. In this study we investigated the regulation of tumor
      necrosis factor-alpha (TNF-alpha) in the expression of MMPs by HSCs. We also
      examined whether the immunosuppressant FK506 influences the MMPs expression in
      human HSCs. Human HSCs, LI90, were treated with TNF-alpha in the presence of
      FK506. Release of MMPs into culture media, levels of MMP-9 mRNA and activation of
      NF-kappaB were compared between the cells cultured with or without FK506.
      Stimulation of human HSCs, LI90 cells, with TNF-alpha caused the induction of pro
      MMP-9. Further, TNF-alpha stimulation induced the degradation of IkappaB-alpha
      and resulted in the transcriptional activation of NF-kappaB. FK506 suppressed
      this TNF-alpha-induced NK-kappaB activation, alone with pro-MMP-9 mRNA and
      protein induction, in HSC. TNF-alpha contributes to the perpetuation of liver
      fibrosis through MMP-9 production from HSCs and that FK506 inhibits the induction
      of MMP-9 through NF-kappaB pathway suggesting the anti-inflammatory properties of
      FK506.

PMID- 16303145
TI  - A novel alternative splice variant of nicastrin and its implication in Alzheimer
      disease.
AB  - Nicastrin interacts with gamma-secretase complex components predominantly via the
      N-terminal third of the transmembrane domain. The authentic transmembrane domain
      is critically required for the interaction with gamma-secretase complex
      components and for formation of an active gamma-secretase complex. In this study,
      we have identified a novel alternatively spliced transcript of nicastrin in human
      brain tissue. This transcript (NCSTN-DeltaE16) lacks exon 16 of nicastrin mRNA,
      which leads to deletion of 71 amino acids just upstream of its transmembrane
      domain. Its expression pattern was analyzed in the hippocampus of patients with
      pathologically diagnosed Alzheimer disease (cases) and non-Alzheimer dementia
      (controls). In patients with the APOE-epsilon4 allele, the frequency of Alzheimer
      disease appeared to be increased in the NCSTN-DeltaE16-positive group, but the
      association was not statistically significant. In conclusion, the expression of
      NCSTN-DeltaE16 transcript may confer some additional risk for developing
      Alzheimer disease beyond the risk due to ApoE-epsilon4 allele. Further
      investigation in larger scale population would be necessary to address its
      potential implication in Alzheimer disease.

PMID- 16303146
TI  - Age- and gender-related difference of ACE2 expression in rat lung.
AB  - Epidemiologic data suggested that there was an obvious predominance of young
      adult patients with a slight female proneness in severe acute respiratory
      syndrome (SARS). The angiotensin-converting enzyme 2 (ACE2) was very recently
      identified as a functional receptor for SARS virus and is therefore a prime
      target for pathogenesis and pharmacological intervention. Rats of both genders at
      three distinct ages (young-adult, 3 months; middle-aged, 12 months; old, 24
      months) were evaluated to determine the characteristic of ACE2 expression in lung
      and the effect of aging and gender on its expression. ACE2 was predominantly
      expressed in alveolar epithelium, bronchiolar epithelium, endothelium and smooth
      muscle cells of pulmonary vessels with similar content, whereas no obvious signal
      was detected in the bronchiolar smooth muscle cells. ACE2 expression is
      dramatically reduced with aging in both genders: young-adult vs. old P < 0.001
      (by 78% in male and 67% in female, respectively) and middle-aged vs. old P <
      0.001 (by 71% in male rats and 59% in female rats, respectively). The decrease of
      ACE2 content was relatively slight between young-adult and middle-aged groups (by
      25% in male and 18% in female, respectively). Although there was no gender
      related difference of ACE2 in young-adult and middle-aged groups, a significantly
      higher ACE2 content was detected in old female rats than male. In conclusion, the
      more elevated ACE2 in young adults as compared to aged groups may contribute to
      the predominance in SARS attacks in this age group.

PMID- 16303147
TI  - Neuroprotective effect of arundic acid, an astrocyte-modulating agent, in mouse
      brain against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity.
AB  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes the damage of
      dopaminergic neurons as seen in Parkinson's disease. Oxidative stress has been as
      one of several pathogenic hypotheses for Parkinson's disease. Here we
      investigated whether arundic acid, an astrocyte-modulating agent, can protect
      against alterations of nitric oxide synthase (NOS) and superoxide dismutase (SOD)
      expression on MPTP neurotoxicity in mice, utilizing an immunohistochemistry. For
      this purpose, anti-tyrosine hydroxylase (TH) antibody, anti-dopamine transporter
      (DAT) antibody, anti-Cu/Zn-SOD antibody, anti-Mn-SOD antibody, anti-nNOS
      antibody, anti-eNOS antibody and anti-iNOS antibody were used. The present study
      showed that the arundic acid had a protective effect against MPTP-induced
      neuronal damage in the striatum and substantia nigra of mice. The protective
      effect may be, at least in part, caused by the reductions of the levels of
      reactive nitrogen (RNS) and oxygen species (ROS) against MPTP neurotoxicity.
      These results suggest that the pharmacological modulation of astrocyte may offer
      a novel therapeutic strategy for the treatment of Parkinson's disease.
      Furthermore, our results provide further evidence that a combination of nNOS
      inhibitors, iNOS inhibitors and free radical scavengers may be effective in the
      treatment of neurodegenerative diseases. Thus our present results provide
      valuable information for the pathogenesis of degeneration of the nigrostriatal
      dopaminergic neuronal pathway.

PMID- 16303148
TI  - Sex differences in the activation of language cortex during childhood.
AB  - Sex differences have been well documented in the behavioral literature but have
      occurred inconsistently in the neuroimaging literature. This investigation
      examined the impact of subject age, language task, and cortical region on the
      occurrence of sex differences in functional magnetic resonance imaging. Two
      hundred and five (104 m, 101 f) right handed, monolingual English speaking
      children between the ages of 5 and 18 years were enrolled in this study. The
      study used fMRI at 3T to evaluate BOLD signal variation associated with sex, age,
      and their interaction. Children completed up to four language tasks, which
      involved listening to stories, prosody processing, single word vocabulary
      identification, and verb generation. A sex difference for behavioral performance
      was found for the prosodic processing task only. Brain activation in the
      classical left hemisphere language areas of the brain and their right homologues
      were assessed for sex differences. Although left lateralization was present for
      both frontal and temporal regions for all but the prosody task, no significant
      sex differences were found for the degree of lateralization. Sex x age
      interaction effects were found for all but the task involving single word
      vocabulary. However effect sizes associated with the sex differences were small,
      which suggests that relatively large sample sizes would be needed to detect these
      effects reliably.

PMID- 16303149
TI  - Cortical correlates of face and scene inversion: a comparison.
AB  - Face recognition is more strongly impaired by stimulus inversion than nonface
      object recognition. This phenomenon, known as the face inversion effect (FIE),
      suggests that the visual system contains specialized processing mechanisms that
      are more engaged by upright faces than by inverted faces or nonface objects.
      Neuroimaging and neuropsychological studies indicate that environmental scenes
      may also recruit specialized-purpose processing machinery but a comparable
      inversion effect for scenes has not been established. Here we demonstrate that
      both face and scene inversion lead to behavioral penalties during performance of
      a continuous visual matching task; however, the scene inversion effect was less
      robust and declined in magnitude over the course of the experiment. Scene
      inversion led to greater neural response in the functionally defined lateral
      occipital (LO) object area for inverted versus upright scenes and reduced
      response in the parahippocampal place area (PPA), while face inversion lead to
      greater response in LO and the right middle fusiform (MF) object area for
      inverted versus upright faces but no change in the fusiform face area (FFA). A
      whole-brain analysis revealed several regions that responded more strongly to
      either upright versus inverted faces or upright versus inverted scenes, some of
      which may be involved in post-recognition processing. These results demonstrate
      that both face and scene inversion cause a shift from specialized processing
      streams towards generic object-processing mechanisms; however, this shift only
      leads to a reliable behavioral penalty in the case of face inversion.

PMID- 16303150
TI  - What have we learned about cognitive development from neuroimaging?
AB  - Changes in many domains of cognition occur with development. In this paper, we
      discuss neuroimaging approaches to understanding these changes at a neural level.
      We highlight how modern imaging methods such as functional magnetic resonance
      imaging (fMRI) and diffusion tensor imaging (DTI) are being used to examine how
      cognitive development is supported by the maturation of the brain. Some reports
      suggest developmental changes in patterns of brain activity appear to involve a
      shift from diffuse to more focal activation, likely representing a fine-tuning of
      relevant neural systems with experience. One of the challenges in investigating
      the interplay between cognitive development and maturation of the brain is to
      separate the contributions of neural changes specific to development and
      learning. Examples are given from the developmental neuroimaging literature. The
      focus is on the development of cognitive control, as the protracted developmental
      course of this ability into adolescence raises key issues. Finally, the relevance
      of normative studies for understanding neural and cognitive changes in
      developmental disorders is discussed.

PMID- 16303151
TI  - Repeated measurements of contrast sensitivity reveal limits to visual plasticity
      after early binocular deprivation in humans.
AB  - Contrast sensitivity improves in visually normal children until 7 years of age
      and is impaired in children who experienced early visual deprivation from
      bilateral congenital cataracts. Here, we investigated whether the deficits after
      early visual deprivation change during childhood by retesting the contrast
      sensitivity of seven patients treated for bilateral congenital cataract who had
      been first tested before 7.5 years of age, and of two patients first tested after
      11 years of age. For the younger group, contrast sensitivity at low spatial
      frequencies improved after 1- and 2-year intervals, while their sensitivity at
      mid and high spatial frequencies did not change. There was no systematic change
      in the two older patients. The results indicate that early visual input sets up
      the neural substrate for later improvement in contrast sensitivity at mid and
      high spatial frequencies. However, there is sufficient plasticity during middle
      childhood to allow some recovery at low spatial frequencies. The results shed new
      light on the role of early visual experience and the nature of developmental
      plasticity.

PMID- 16303152
TI  - Temporal and probabilistic discounting of rewards in children and adolescents:
      effects of age and ADHD symptoms.
AB  - This study investigated whether age and ADHD symptoms affected choice preferences
      in children and adolescents when they chose between (1) small immediate rewards
      and larger delayed rewards and (2) small certain rewards and larger probabilistic
      uncertain rewards. A temporal discounting (TD) task and a probabilistic
      discounting (PD) task were used to measure the degree to which the subjective
      value of a large reward decreased as one had to wait longer for it (TD), and as
      the probability of obtaining it decreased (PD). Rewards used were small amounts
      of money. In the TD task, the large reward (10 cents) was delayed by between 0
      and 30s, and the immediate reward varied in magnitude (0-10 cents). In the PD
      task, receipt of the large reward (10 cents) varied in likelihood, with
      probabilities of 0, 0.25, 0.5, 0.75, and 1.0 used, and the certain reward varied
      in magnitude (0-10 cents). Age and diagnostic group did not affect the degree of
      PD of rewards: All participants made choices so that total gains were maximized.
      As predicted, young children, aged 6-11 years (n = 25) demonstrated steeper TD of
      rewards than adolescents, aged 12-17 years (n = 21). This effect remained
      significant even when choosing the immediate reward did not shorten overall task
      duration. This, together with the lack of interaction between TD task version and
      age, suggests that steeper discounting in young children is driven by reward
      immediacy and not by delay aversion. Contrary to our predictions, participants
      with ADHD (n = 22) did not demonstrate steeper TD of rewards than controls (n =
      24). These results raise the possibility that strong preferences for small
      immediate rewards in ADHD, as found in previous research, depend on factors such
      as total maximum gain and the use of fixed versus varied delay durations. The
      decrease in TD as observed in adolescents compared to children may be related to
      developmental changes in the (dorsolateral) prefrontal cortex. Future research
      needs to investigate these possibilities.

PMID- 16303153
TI  - EEG spectral power and cognitive performance during sleep inertia: the effect of
      normal sleep duration and partial sleep deprivation.
AB  - Sleep inertia (SI) is a transient period occurring immediately after awakening,
      usually characterized by performance decrement. When sleep is sufficient, SI is
      moderate, and produces few or no deficit. When it is associated with prior sleep
      deprivation, SI shows dose-dependent negative effects on cognitive performance,
      especially when subjects have been awaken in slow wave sleep (SWS). In the
      present study, spectral analysis was applied during the last 10 min before and
      the first 10 min after awakening, and during 1 h after awakening while subjects
      performed the Stroop test. Seventeen subjects were divided into a Control group
      who slept 8 h, and a Sleep Deprived group who slept only 2 h. The results show
      that performance was normal in the Control group, whereas reaction time was
      increased during the first half hour and error level during the second half hour
      in the Sleep Deprived group. Spectral analysis applied on the waking EEG during
      the whole test session showed that alpha activity was increased in both groups,
      but theta power only in the Sleep Deprived group. There was a high positive
      correlation in sleep deprived subjects between delta power during the last 10 min
      of sleep and subsequent performance decrement in speed and accuracy. Comparison
      of individual records showed a high positive correlation between spectral power
      before and after awakening in the Control group (generally in the sense of an
      increased frequency band), but no correlation was found in the Sleep Deprived
      group who exhibited a rather disorganized pattern. We discuss these results in
      terms of incoherence in the EEG continuity during sleep offset after prior sleep
      loss, which could partly account for the performance decrement observed during SI
      in sleep deprived subjects.

PMID- 16303154
TI  - l-DOPA improves odor discrimination learning in rats.
AB  - Using a forced-choice odor discrimination task in rats, we show here that
      intraperitoneal injections of l-DOPA improve rats' odor discrimination
      performance in comparison to control rats injected with saline. Although the
      exact mechanism of l-DOPA and potential action on dopamine receptors remains
      unclear, the present results indicate that rats injected with the 20-50 mg/kg of
      l-DOPA performed significantly better in an odor discrimination task than did
      control rats. In addition, we observed a significant correlation between the
      concentration of l-DOPA and odor discrimination performance.

PMID- 16303155
TI  - Phytochemical constituents and hepatoprotective activity of Viburnum tinus.
AB  - From the leaves of Viburnum tinus L. (Adoxaceae) two acylated iridoid glucosides
      (viburtinoside A and B), a coumarin diglucoside scopoletin 7-O-beta-D-sophoroside
      and a natural occurred dinicotinic acid ester 2,6-di-C-methyl-nicotinic acid 3,5
      diethyl ester were isolated. In addition to these, 10 known compounds were
      isolated, namely two bidesmosidic saponins, a hexamethoxy-flavone and five
      flavonol glycosides, as well as suspensolide A and oleanolic acid were isolated
      for the first time in this genus and species, respectively. The structures were
      determined mainly by spectroscopic methods (UV, IR, ESI-MS, 1H-, 13C NMR and
      DEPT). Toxicity of the investigated extract was determined (LD50=500 mg/kg). CCl4
      induced hepatotoxicity has been evaluated in terms of the determination of
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipid peroxide
      and nitric oxide levels in serum and compared using adult male rats weighing 150
      180 g. Their highly elevated levels were significantly reduced by treatment with
      the investigated aqueous methanol extract in dose-dependent manner.

PMID- 16303156
TI  - Community-based monitoring of diarrhea in urban Brazilian children: incidence and
      associated pathogens.
AB  - Community-based monitoring was conducted in order to investigate the occurrence
      of diarrhea in 'sentinel areas' of Salvador, Brazil, and to establish a
      preliminary profile of the most common pathogens present in children's diarrhea
      by screening stool samples. This report describes the results obtained from twice
      weekly home visits to identify and follow diarrhea episodes and testing of carer
      requested stool sample collection over a 6-month period. Participants were
      selected from a large longitudinal study in 21 areas representing the city's
      poorer socioeconomic and sanitary conditions. Fecal samples were examined for the
      presence of pathogenic bacteria, viruses and protozoa. The mean incidence of
      diarrhea was 4.97 episodes per child-year, and longitudinal prevalence was 13.6
      days per child-year (3.7%). Pathogens were found in 44% of the fecal samples
      examined. Bacteria were the most frequently encountered pathogens (isolated in
      22% of samples), followed by protozoa (19.5%) and viruses (16%). Viral and
      bacterial pathogens were associated with episodes of severe diarrhea, while viral
      and protozoan pathogens were associated with longer episodes. The study
      demonstrated the importance of a public health monitoring system based on
      'sentinel areas'.

PMID- 16303157
TI  - Ornithosaponins A-D, four new polyoxygenated steroidal glycosides from the bulbs
      of Ornithogalumthyrsoides.
AB  - By analyzing the steroidal glycoside content of fresh bulbs of Ornithogalum
      thyrsoides (Liliaceae), we were able to isolate four new polyoxygenated steroidal
      glycosides, which we named ornithosaponins A-D (1-4). The structures of 1-4 were
      elucidated on the basis of extensive spectroscopic analysis, including that of 2D
      NMR data, and the results of acidic or alkaline hydrolysis. The aglycone
      structure of 1-4 has not been previously reported. It is also notable that
      ornithosaponins B-D (2-4) have been found to contain 6-deoxy-beta-D-gulopyranose
      as a sugar component, which is rarely encountered in plant glycosides.

PMID- 16303158
TI  - Envenomation by Amazonian freshwater stingray Potamotrygon motoro: 2 cases
      reported in Europe.
AB  - Freshwater stingrays of the Potamotrygon genus are regarded by native people in
      the Amazonia as dangerous fishes responsible of frequent stings. Small freshwater
      stingrays are imported to Europe and sold as aquarium fish because they are easy
      to keep captive. The purpose of this report is to describe two new cases
      involving envenomation by freshwater stingray. One patient was an experienced 45
      year-old French hobbyist. The second patient was a 35-year-old German pet store
      assistant. The clinical picture in both cases featured severe local pain with
      minimal systemic manifestations. Both patients recovered fully after symptomatic
      treatment. These two cases of envenomation call attention to the potential for
      injury among persons in close contact with venomous pets.

PMID- 16303159
TI  - Calcium plays a key role in the effects induced by a snake venom Lys49
      phospholipase A2 homologue on a lymphoblastoid cell line.
AB  - A catalytically-inactive Lys49 phospholipase A2 homologue from the venom of the
      snake Bothrops asper induces diverse effects (necrosis, apoptosis and
      proliferation) in a lymphoblastoid cell line, depending on the toxin
      concentration. The increments in cytosolic Ca2+ levels induced by this toxin in
      this cell line were assessed. At high toxin concentration (100 microg/mL) the
      toxin induces drastic disruption of the plasma membrane, associated with a
      prominent Ca2+ influx and necrosis. Previous incubation of the cells with the
      chelating agent EGTA or with ruthenium red, an inhibitor of the uniporter
      mitochondrial Ca2+ transport, greatly reduced necrosis. At a toxin concentration
      of 12.5 microg/mL, apoptosis is the predominant response, being associated with
      lower increments in cytosolic Ca2+. This effect was inhibited by preincubation
      with ruthenium red and the cytosolic Ca2+ chelator BAPTA-AM. The proliferative
      response, which occurs at a low toxin concentration (0.5 microg/mL), is
      associated with a small and oscillatory increment in cytosolic Ca2+. It was
      inhibited by EGTA, ruthenium red and BAPTA-AM, by inhibitors of the endoplasmic
      reticulum Ca2+ -ATPase (SERCA) and by blockade of the ryanodine receptor. It is
      concluded that necrosis and apoptosis induced by this toxin are associated with
      increments in cytosolic Ca2+ levels following plasma membrane perturbation,
      together with the involvement of mitochondria. The cellular proliferative
      response depends on a limited Ca2+ influx through the plasma membrane, being
      associated with a concerted functional unit constituted by SERCA, the ryanodine
      receptor and mitochondria, which regulate the observed oscillations in cytosolic
      Ca2+ concentration.

PMID- 16303160
TI  - SARS coronavirus 7a protein blocks cell cycle progression at G0/G1 phase via the
      cyclin D3/pRb pathway.
AB  - The genome of severe acute respiratory syndrome-associated coronavirus (SARS-CoV)
      contains four structural genes that are homologous to genes found in other
      coronaviruses, and also contains six subgroup-specific open reading frames
      (ORFs). Expression of one of these subgroup-specific genes, ORF7a, resulted in
      apoptosis via a caspase-dependent pathway. Here, we observed that transient
      expression of ORF7a protein fused with myc or GFP tags at its N or C terminus
      inhibited cell growth and prevented BrdU incorporation in different cultural
      cells, suggesting that ORF7a expression may regulate cell cycle progression.
      Analysis by flow cytometry demonstrated that ORF7a expression was associated with
      blockage of cell cycle progression at G0/G1 phase in HEK 293 cells after 24 to 60
      h post-transfection. Similar results were observed in COS-7 and Vero cells.
      Mutation analysis of ORF7a revealed that the domain spanning aa 44-82 of 7a
      protein was essential for its cytoplasmic localization and for induction of the
      cell cycle arrest. After analyzing the cellular proteins involving in regulation
      of cell cycle progression, we demonstrated that ORF7a expression was correlated
      with a significant reduction of cyclin D3 level of mRNA transcription and
      expression, and phosphorylation of retinoblastoma (Rb) protein at ser795 and
      ser809/811, not with the expression of cyclin D1, D2, cdk4 and cdk6 in HEK 293
      cells. These results suggest that the insufficient expression of cyclin D3 may
      cause a decreased activity of cyclin D/cdk4/6, resulting in the inhibition of Rb
      phosphorylation. Accumulation of hypo- or non-phosphorylated pRb thus prevents
      cell cycle progression at G0/G1 phase.

PMID- 16303161
TI  - Ubiquitination of APOBEC3 proteins by the Vif-Cullin5-ElonginB-ElonginC complex.
AB  - APOBEC3 proteins are antiviral host factors for a wide variety of retroviruses.
      HIV-1 Vif overcomes the antiviral activity of APOBEC3G by ubiquitinating the
      protein. In this study, we examined the ability of Vif to antagonize other family
      members of APOBEC3 proteins, together with its mechanism. Using HIV infectivity,
      virion incorporation, immunoprecipitation, and in vitro ubiquitin conjugation
      assays, we show that the ability of Vif to inhibit antiviral activity of APOBEC3
      proteins positively correlates with its ability to bind and ubiquitinate these
      proteins by a Vif-Cullin5-ElonginB-ElonginC (Vif-BC-Cul5) complex. These results
      suggest that Vif exhibits its anti-APOBEC3 activity by the ubiquitin ligase
      activity of the Vif-BC-Cul5 complex.

PMID- 16303162
TI  - Prolonged activation of NF-kappaB by human cytomegalovirus promotes efficient
      viral replication and late gene expression.
AB  - Infection of fibroblasts by human cytomegalovirus (HCMV) rapidly activates the NF
      kappaB signaling pathway, which we documented promotes efficient transactivation
      of the major immediate-early promoter (DeMeritt, I.B., Milford, L.E., Yurochko,
      A.D. (2004). Activation of the NF-kappaB pathway in human cytomegalovirus
      infected cells is necessary for efficient transactivation of the major immediate
      early promoter. J. Virol. 78, 4498-4507). Because a second, sustained increase in
      NF-kappaB activity following the initial phase of NF-kappaB activation was also
      observed, we investigated the role that this prolonged NF-kappaB activation
      played in viral replication and late gene expression. We first investigated HCMV
      replication in cells in which NF-kappaB activation was blocked by pretreatment
      with NF-kappaB inhibitors: HCMV replication was significantly decreased in these
      cultures. A decrease in replication was also observed when NF-kappaB was
      inhibited up to 48 h post-infection, suggesting a previously unidentified role
      for NF-kappaB in the regulation of the later class of viral genes.

PMID- 16303163
TI  - Nitrobacter and Nitrospira genera as representatives of nitrite-oxidizing
      bacteria: detection, quantification and growth along the lower Seine River
      (France).
AB  - Pollution from agriculture and urban effluents influences the ecology and
      biochemical functioning of the Seine River. Nitrification dominates nitrogen
      transformations downstream of the effluents of the Paris wastewater treatment
      plant (WWTP) at Acheres, treating, by activated sludge the wastewater of 6.5
      million inhabitant equivalents from Paris and its suburbs, without nitrification
      and denitrification treatment. It discharges effluents containing large amounts
      of nitrogen, ammonium mostly (approximately 30 mg L(-1) N-NH(4+) L(-1)), on
      average 45 mg L(-1) of suspended particulate matter, high quantities of total
      organic carbon (approximately 30 mg C L(-1)) largely biodegradable (40%), and
      high concentration in total phosphorus ( approximately 3 mg Tot P L(-1)), as well
      as microorganisms. Ammonium, brought into the river system, is slowly nitrified
      in the lower Seine River and especially in the freshwater estuary. The nitrifying
      activities can be observed by measuring inorganic nitrogen compound
      concentrations and potential activities. To understand the contributions of the
      WWTP effluents, the upstream agricultural runoff water and the Seine tributaries,
      it is useful to investigate the bacterial community. Whereas ammonia oxidation
      has been widely studied, the second step, i.e. nitrite oxidation, is less well
      understood. We have previously analysed the ammonium-oxidizing bacterial (AOB)
      community in the Seine (Cebron, A., Berthe, T., Garnier, J., 2003. Nitrification
      and nitrifying bacteria in the lower Seine River and estuary (France). Appl.
      Environ. Microbiol. 69, 7091-7100; Cebron, A., Coci, M., Garnier, J., Laanbroek,
      H.J., 2004. DGGE analysis of the ammonia oxidizing bacterial community structure
      in the lower Seine River: impact of the Paris wastewater effluents. Appl.
      Environ. Microbiol. 70, 6726-6737), and focus here on the composition of the
      nitrite-oxidizing bacterial (NOB) community. As no general molecular probe
      targeting all known NOBs is currently available, we chose to target and quantify
      (by competitive PCR) the two genera Nitrobacter and Nitrospira assumed to be the
      major players in nitrite oxidation in freshwater environments. Nitrobacter
      species were dominant in the upstream Seine River basin but Nitrospira was the
      dominant NOB downstream of the WWTP. These two genera were equally represented in
      WWTP effluents. In the Seine River estuary, especially in the salinity gradient,
      the Nitrobacter proportion increases and that of Nitrospira disappears, possibly
      due dilution by seawater.

PMID- 16303164
TI  - Short-term physiological responses to a severe acid stress in three
      macroinvertebrate species: a comparative study.
AB  - The present study focuses on the sensitivity among freshwater invertebrate
      species to acidic stress. Three common macroinvertebrate species in the Vosges
      Mountains (North-Eastern France), Gammarus fossarum (Amphipoda), Hydropsyche
      pellucidula (Trichoptera) and Dinocras cephalotes (Plecoptera) were exposed for
      24, 72 and 120 h to natural acidified water (pH=4.73+/-0.08, [Ca2+]=39.1+/-0.6
      micromol l(-1), [Al(tot)]=28.4+/-1 micromol l(-1)). Short-term exposure to acid
      stress caused significant decreases both in survival rate and haemolymph ions
      ([Cl-] and [Na+]). The relative sensitivity to a natural acidic stress slightly
      differed among the species and was in the following order: G. fossarum, as the
      most sensitive, then H. pellucidula and D. cephalotes. Results of this study
      confirm the interest of in situ tests to assess the toxicity of short-term acid
      exposure. Finally, our results reinforce the hypothesis that transient
      acidification can offset the recovery of sensitive species of macroinvertebrates
      in streams chemically recovering from acidification either through liming or
      declining deposition.

PMID- 16303166
TI  - Ferrate(VI): green chemistry oxidant for degradation of cationic surfactant.
AB  - Iron in its familiar form exists in the +2 and +3 oxidation states, however,
      higher oxidation state of iron +6, ferrate(VI) (Fe(VI)O(4)(2-)) can be obtained.
      The high oxidation power of ferrate(VI) can be utilized in developing cleaner
      ("greener") technology for remediation processes. This paper demonstrates the
      unique property of ferrate(VI) to degrade almost completely the cationic
      surfactant, cetylpyridinium chloride (C(5)H(5)N(+)(CH(2))(15)CH(3).H(2)O Cl(-),
      CPC). The Rate law for the oxidation of CPC by ferrate(VI) at pH 9.2 was found to
      be: -d[Fe(VI)]/dt = k[Fe(VI)][CPC](2). Ferrate(VI) oxidizes CPC within minutes
      and molar consumption of ferrate(VI) was nearly equal to the oxidized CPC. The
      decrease in total organic carbon (TOC) from CPC was more than 95%; suggesting
      mineralization of CPC to carbon dioxide. Ammonium ion was the other product of
      the oxidation. This is the first report in which Fe(VI)O(4)(2-) ion opens the
      pyridine ring and mineralizes the aliphatic chain of the organic molecule giving
      inorganic ions.

PMID- 16303165
TI  - A method for determination of methyl chloride concentration in air trapped in ice
      cores.
AB  - A method for measuring the concentration of methyl chloride (CH3Cl) in air
      trapped in an ice core was developed. The method combines the air extraction by
      milling the ice core samples under vacuum and the analysis of the extracted air
      with a cryogenic preconcentration/gas chromatograph/mass spectrometry system. The
      method was applied to air from Antarctic ice core samples estimated to have been
      formed in the pre-industrial and/or early industrial periods. The overall
      precision of the method deduced from duplicate ice core analyses was estimated to
      be better than +/-20 pptv. The measured CH3Cl concentration of 528+/-26 pptv was
      similar to the present-day concentration in the remote atmosphere as well as the
      CH3Cl concentration over the past 300 years obtained from Antarctic firn air and
      ice core analyses.

PMID- 16303167
TI  - The influence of paddy soil drying on Tc insolubilization by bacteria.
AB  - Tc insolubilization in four soils samples was compared by pre-incubating them in
      both dry and wet states, then measuring Tc concentrations in solution when the
      samples were saturated with an excess of water spiked with 99Tc. Soils pre
      incubated in a dry state showed higher Tc insolubilization than soils incubated
      in a wet state. To clarify the difference in Tc insolubilization, Eh, bacterial
      abundances, and bacterial species compositions in the dry and wet ponding water
      samples were determined. For the wet ponding water samples, Eh values were forced
      to decrease, but no increase in Tc insolubilization was observed. The dry and wet
      ponding water samples had similar numbers of bacteria. However, denaturing
      gradient gel electrophoresis analysis revealed that they had different bacterial
      species compositions. These results suggested the difference in bacterial species
      compositions would account for the difference in Tc insolubilization.

PMID- 16303168
TI  - Uptake and elimination of perchlorate in eastern mosquitofish.
AB  - The purpose of this study was to investigate the uptake and elimination of
      perchlorate in eastern mosquitofish (Gambusia holbrooki). Fish were exposed to
      0.1-1000 mg/l sodium perchlorate for 12h, 1, 2, 5, 10, and 30 days, and
      perchlorate was determined in whole body extracts. Perchlorate was not detected
      in mosquitofish exposed to the low concentrations of perchlorate (0, 0.1, and
      1mg/l sodium perchlorate), regardless of the exposure time, whereas it was
      detected when fish were exposed to 10, 100, and 1000 mg/l. The tissue
      concentrations were approximately 10 times less than that in the water. There was
      no difference in the uptake of perchlorate depending upon the exposure time,
      however, a difference in perchlorate uptake depending upon the concentration of
      the exposure dose (P<0.001) was observed. Uptake (K(u)) and elimination (K(e))
      rate constants were 0.09 l/mg day and 0.70 day(-1), respectively. The half-life
      (T1/2) of perchlorate was 0.99 day. Thus, it appears that perchlorate is rapidly
      taken up and eliminated in eastern mosquitofish. These results are critical and
      may be used to develop models of fate, effects, and transport of perchlorate in
      natural systems, as well as to assess ecological risk in affected ecosystems.

PMID- 16303169
TI  - Changes in nutrient concentrations and ratios during mucilage events in the
      period 1999-2002.
AB  - Nutrient and chlorophyll a concentrations and salinity were measured,
      approximately monthly, from June 1999 to July 2002 at 20 stations along three
      transects in the northern Adriatic Sea, north of the line Susak Island
      Senigallia, with the aim of confirming or rejecting the hypothesis that changes
      in nutrient ratios may have an important role in the mucilage phenomenon. The
      data analyses were focused on the two major water types identified in the region:
      lower salinity (32-37) and oxygenated surface waters (type 1) in which the
      mucilage phenomenon primarily developed, and high salinity water originating from
      other parts of the Adriatic (type 4). Marked variability of dissolved inorganic
      nitrogen (DIN) in type 1 waters was roughly correlated with extreme fluctuations
      of the Po River flow rate during the investigated period. In contrast, the
      orthophosphate (PO4) concentration was primarily controlled by phytoplankton
      assimilation. The nutrient discharges and DIN/PO4 ratios (median 120) in the
      freshened surface layer were much higher and more variable in the period before
      the mucilage event in 2001 than in 2000 (median 75), and particularly in 2002
      (median 30), although intensity and duration of the 2001 event were the lowest.
      However, in that period of 2000 and 2002 significant transversal transport of
      freshened waters occurred, despite the unusually low Po flow rates. In summer, in
      conditions of low freshwater discharge and the prevailing of semi-enclosed
      circulation in the region, more efficient DIN assimilation by phytoplankton
      occurred, probably due to a faster recycling of PO4. However, in 2002 this
      process appeared to have already started in March. Changes of the orthosilicate
      (SiO4)/DIN ratio were mainly dependent on DIN concentrations. In the more saline
      waters (type 4) the nutrient concentrations, particularly DIN, were much lower
      and no significant relationships were noticed among the studied parameters.
      Nutrient concentration and ratio changes do not trigger mucilage events, although
      very probably they have an essential role in combination with several other
      physical (pulsing freshwater discharge, marked stratification, minimal water
      exchange) and biological (e.g., increased plankton excretion, limited bacterial
      degradation) factors.

PMID- 16303170
TI  - Tumorigenesis of K-ras mutation in human endometrial carcinoma via upregulation
      of estrogen receptor.
AB  - OBJECTIVE: To investigate the tumorigenesis of mutant [12Asp]-K-ras in
      endometrial carcinoma and its relationship with ER. METHODS: We constructed pcDI
      [12Asp]K-ras4B by inserting full-length [12Asp]K-ras4B from human endometrial
      carcinoma Hec-1A cells, into pcDI vector. Cell proliferation of NIH3T3 after
      transfection with pcDI-[12Asp]K-ras4B was measured by MTT assay. The cell
      transformation was determined by colony formation and tumor nodule development.
      [12Asp]-K-ras4B-NIH3T3 cells were transfected with constitutively active pCMV
      RafCAAX and dominant-negative pCMV-RafS621A. Cell growth was measured by MTT
      assay and [3H]thymidine incorporation. After transfected with pcDI-[12Asp]K-ras4B
      or pCMV-RafS621A, the cells were harvested for Western blot and reporter assay to
      determine the expression and transcriptional activity of ERalpha and ERbeta,
      respectively. RESULTS: [12Asp]-K-ras4B enhanced NIH3T3 cells proliferation after
      48 h post-transfection (P < 0.05). More colonies were grown 10 days after
      incubating pcDI-[12Asp]-K-ras4B-NIH3T3 cells (13.48%) than pcDI-NIH3T3 (4.26%) or
      untreated NIH3T3 (2.33%). The pcDI-[12Asp]-K-ras4B-NIH3T3 cells injected to the
      nude mice Balb/C developed tumor nodules with poor-differentiated cells after 12
      days. An increase of ERalpha and ERbeta was observed in pcDI-[12Asp]-K-ras4B
      NIH3T3 cells. RafS621A downregulated ERalpha and ERbeta expression. Estrogen
      induced the ER transcriptional activity by 5-fold in pcDI-NIH3T3 cells, 13-fold
      in pcDI-[12Asp]K-ras4B-NIH3T3 and 19-fold in HEC-1A. RafS621A suppressed the ER
      transcriptional activity. CONCLUSIONS: K-ras mutation induces tumorigenesis in
      endometrium, and this malignant transformation involves Raf signaling pathway and
      ER.

PMID- 16303171
TI  - Maternal programming of steroid receptor expression and phenotype through DNA
      methylation in the rat.
AB  - Increased levels of pup licking/grooming and arched-back nursing by rat mothers
      over the first week of life alter the epigenome at a glucocorticoid receptor gene
      promoter in the hippocampus of the offspring. Differences in the DNA methylation
      pattern between the offspring of High and Low licking/grooming--arched-back
      mothers emerge over the first week of life, are reversed with cross-fostering,
      persist into adulthood and are associated with altered histone acetylation and
      transcription factor (NGFI-A) binding to the glucocorticoid receptor promoter.
      Central infusion of the adult offspring with the histone deacetylase inhibitor
      trichostatin A removes the previously defined epigenomic group differences in
      histone acetylation, DNA methylation, NGFI-A binding, glucocorticoid receptor
      expression, and hypothalamic-pituitary-adrenal responses to stress, thus
      suggesting a causal relation between the epigenomic state, glucocorticoid
      receptor expression and the effects of maternal care on stress responses in the
      offspring. These findings demonstrate that an epigenomic state of a gene can be
      established through a behavioral mode of programming and that in spite of the
      inherent stability of this epigenomic mark, it is dynamic and potentially
      reversible.

PMID- 16303172
TI  - An approach for producing transgenic cloned cows by nuclear transfer of cells
      transfected with human alpha 1-antitrypsin gene.
AB  - In an attempt to produce transgenic cloned cows secreting alpha 1-antitrypsin
      (alpha1-AT) protein into milk, bovine cumulus cells were transfected with a
      plasmid containing an alpha1-AT gene and green fluorescent protein (GFP) reporter
      gene using Fugene 6 as a lipid carrier. The GFP-expressing cells were selected
      and transferred into enucleated bovine oocytes. Couplets were fused, chemically
      activated and cultured. Developmental competence was monitored and the number of
      inner cell mass (ICM) and trophectoderm (TE) cells in blastocysts were counted
      after differential staining. The percentage of blastocysts was lower (P < 0.05)
      in transgenic cloned embryos compared to non-transgenic cloned embryos (23%
      versus 35%). No difference in the numbers of ICM and TE cells between the two
      groups of embryos was observed. One or two GFP-expressing blastocysts were
      transferred into the uterus of each recipient cow. Out of 49 recipient cows,
      three pregnancies were detected by non-return estrus and rectal palpation.
      However, the pregnancies failed to maintain to term; two fetuses were aborted at
      Day 60 and 150, respectively, and one fetus at Day 240. The genomic DNA from the
      aborted fetus was amplified by polymerase chain reaction (PCR) to investigate
      integration of the transgene in the fetus. The expected PCR product was sequenced
      and was identical to the sequence of alpha1-AT transgene. In conclusion, the
      present study demonstrated that developmental competence of cloned embryos
      derived from transgenic donor cells was lower than embryos derived from non
      transfected donor cells. Although we failed to obtain a viable transgenic cloned
      calf, integration of alpha1-AT gene into the fetus presents the possibility of
      producing transgenic cloned cows by somatic cell nuclear transfer.

PMID- 16303173
TI  - Water uptake of bonding systems applied on root dentin surfaces: a SEM and
      confocal microscopic study.
AB  - OBJECTIVES: Dentin adhesives have been proposed as desensitizing agents to seal
      exposed root dentin surfaces. Simplified 'one-step' dentin adhesives are highly
      permeable to water. The authors hypothesized that a lactic acid challenge may
      increase permeability of simplified adhesives and may induce fast degradation of
      bonding. This phenomenon adversely affects their durability as long term
      desensitizing agents. The aim of this in vitro study was to evaluate the ability
      of four dentin adhesives to seal root dentin surfaces that were exposed to water
      and lactic acid challenges. METHODS: Four commercially-available dentin adhesives
      were applied with a small sponge to the root dentin of extracted human molars as
      de-sensitizing agents. Impression replicas of the adhesive-covered root dentin
      were fabricated after water immersion, as a control, and after lactic acid
      challenge. The replicas were examined with SEM for quantitative comparison of
      fluid droplet formation on the surfaces. The bonded specimens were also examined
      using reflected light confocal microscopy. RESULTS: Replicas of water droplets
      were observed on the adhesive surfaces, by SEM which corresponded with direct
      confocal observation of blisters and voids from the surface of the bonded
      specimens. There were significantly more water droplets from samples that were
      subjected to lactic acid challenge than water only immersion. SIGNIFICANCE:
      Although the dentin adhesives examined were able to cover exposed root dentin,
      they all exhibited fluid transudation through the polymerized adhesives. Dentin
      adhesives were also susceptible to surface degradation after lactic acid
      challenge. As simplified self-etch adhesives were highly water permeable and
      exhibited the most extensive surface damage, they may not be the best adhesives
      to be used for long-term dentin desensitization. These preliminary in vitro
      findings warrant validation in vivo.

PMID- 16303174
TI  - Wet spinning of Bombyx mori silk fibroin dissolved in N-methyl morpholine N-oxide
      and properties of regenerated fibres.
AB  - Silk fibroin (SF) was dissolved in N-methyl morpholine N-oxide (NMMO) at a
      polymer concentration of 13% (w/w); thermal and rheological solution properties
      were characterized. The melting/crystallization behaviour of NMMO was influenced
      by SF presence. Melting of NMMO hydrate decreased to 71 degrees C and a cold
      crystallization peak appeared at 35 degrees C on heating. None crystallization
      occurred on cooling. Quenching at a temperature of 50 degrees C or higher did not
      induce any crystallization on heating. Viscosity of SF-NMMO solutions decreased
      as a function of temperature. At 75 degrees C, viscosity remained constant for
      360 min. SF-NMMO dope was spun by using a lab-scale wet spinning line. The
      extruded filament was coagulated in an ethanol bath. Regenerated SF fibres were
      collected at different draw ratios and their morphological, physical, and
      mechanical properties were characterized. Fibre diameters ranged from 133 to
      19mum, cross-section was regularly circular, and surface was generally smooth,
      with a very fine granular aspect. Birefringence increased with increasing the
      draw ratio, especially when take up and post-spinning draw were coupled. FT-IR
      spectra and DSC thermograms confirmed that SF fibres crystallized into Silk II
      structure. The IR crystallinity index did not change as a function of drawing.
      Regenerated SF fibres undrawn or drawn only during the coagulation step showed
      the mechanical behaviour typical of a brittle material. However, when both take
      up and post-spinning draw were applied, fibres displayed a ductile-stable
      behaviour. Typical values of the mechanical parameters of regenerated SF fibres
      were: E=8.7 GPa, sigma(b)=120 MPa and epsilon(b)=35%.

PMID- 16303175
TI  - Fatigue crack propagation resistance of virgin and highly crosslinked, thermally
      treated ultra-high molecular weight polyethylene.
AB  - To prolong the life of total joint replacements, highly crosslinked ultra-high
      molecular weight polyethylenes (UHMWPEs) have been introduced to improve the wear
      resistance of the articulating surfaces. However, there are concerns regarding
      the loss of ductility and potential loss in fatigue crack propagation (FCP)
      resistance. The objective of this study was to evaluate the effects of gamma
      radiation-induced crosslinking with two different post-irradiation thermal
      treatments on the FCP resistance of UHMWPE. Two highly crosslinked and one virgin
      UHMWPE treatment groups (ram-extruded, orthopedic grade, GUR 1050) were examined.
      For the two highly crosslinked treatment groups, UHMWPE rods were exposed to 100
      kGy and then underwent post-irradiation thermal processing either above the melt
      temperature or below the melt temperature (2 h-150 degrees C, 110 degrees C).
      Compact tension specimens were cyclically loaded to failure and the fatigue crack
      growth rate, da/dN, vs. cyclic stress intensity factor, DeltaK, behavior was
      determined and compared between groups. Scanning electron microscopy was used to
      examine fracture surface characteristics. Crosslinking was found to decrease the
      ability of UHMWPE to resist crack inception and propagation under cyclic loading.
      The findings also suggested that annealing as a post-irradiation treatment may be
      somewhat less detrimental to FCP resistance of UHMWPE than remelting. Scanning
      electron microscopy examination of the fracture surfaces demonstrated that the
      virgin treatment group failed in a more ductile manner than the two highly
      crosslinked treatment groups.

PMID- 16303176
TI  - Angiotensin II-induced changes of calcium sparks and ionic currents in human
      atrial myocytes: potential role for early remodeling in atrial fibrillation.
AB  - AIMS: Atrial angiotensin II (ANG II) levels have been shown to be increased in
      atrial fibrillation (AF). The purpose of the study was to evaluate a potential
      role of ANG II in the early remodeling and susceptibility to chronicization of
      AF. METHODS AND RESULTS: Isolated human atrial myocytes were incubated in ANG II
      and/or angiotensin type 1 receptor blocker candesartan. ANG II markedly increased
      the frequency of spontaneous Ca(2+) sparks, spark full duration, time to peak
      Ca(2+) fluorescence and decay time measured by confocal imaging. Sarcoplasmic
      reticulum calcium content estimated by caffeine-evoked calcium release did not
      differ between ANG II-treated cells and controls. Patch-clamp recordings revealed
      that ANG II significantly decreased I(to) and increased I(Ca,L) current
      densities. Candesartan blocked these ANG II-mediated alterations. ANG II
      exhibited no effect on I(K1), I(Kur) and I(f) current size. Expression of
      connexin 40 and connexin 43 was not significantly changed by ANG II as assessed
      by immunohistochemistry and Western blot analysis. CONCLUSION: ANG II-induced
      alterations of calcium handling and electrophysiological changes in human atrial
      cells similar to those previously observed in the onset of AF. Prevention of
      these alterations by candesartan might constitute a useful pharmacological
      strategy for the treatment of AF.

PMID- 16303177
TI  - Tuning caged calcium: photolabile analogues of EGTA with improved optical and
      chelation properties.
AB  - The physico-chemical properties of several Ca(2+)-selective, photolabile
      chelators are described. These molecules have been developed as part of an effort
      to produce a caged Ca(2+) that improved upon the Ca(2+) chelation properties and
      light absorption capability of nitrophenyl-EGTA (NP-EGTA). Four dimethoxy-ortho
      nitrophenyl derivatives of EGTA (called DMNPE-1 through -4), and one analogue of
      EGTA (DMNPE-5) have been characterized, each of which is bisected upon
      irradiation. One of these cages has a higher affinity than NP-EGTA: DMNPE-4 has a
      K(d) for Ca(2+) of 48 nm at pH 7.2 (19 nM at pH 7.4). Furthermore, this cage has
      a large extinction coefficient of 5120 M(-1)cm(-1) at 350 nm (cf. 975 M(-1)cm(-1)
      for NP-EGTA). The other physico-chemical properties of DMNPE-4 are: quantum yield
      of photolysis of 0.09; bipasic Ca(2+) release kinetics (70% released with a rate
      of about 48,000 s(-1) and 30% at 1.5s(-1)) and photoproducts that bind Ca(2+)
      with very low affinity (K(d) in the range of 2mM, pH 7.2), hence most of the
      bound Ca(2+) is released rapidly and efficiently upon photolysis. Thus, DMNPE-4
      has a unique combination of properties that make it an extremely effective Ca(2+)
      cage.

PMID- 16303178
TI  - Non-anthracycline based remission induction therapy for newly diagnosed patients
      with acute myeloid leukemia aged 60 or older.
AB  - We assessed remission rates and toxicity in 24 consecutive elderly (age>or=60)
      patients with untreated Acute myeloid leukemia (AML) who received the
      anthracycline-free combination of fludarabine, cytosine arabinoside and G-CSF
      (FLAG) as initial induction chemotherapy at our center. CR was achieved following
      one cycle of FLAG in 14 patients (58%). Another four patients cleared blasts from
      their bone marrow by day 30 without complete platelet recovery. Three patients
      died from infections prior to neutrophil recovery (12%). No other grade 3/4
      toxicities and no clinically significant mucositis were seen. No significant
      association was found between age, WBC and cytogenetic risk group with likelihood
      of achieving CR. Fifteen patients proceeded to consolidation therapy and seven
      patients received a stem cell transplant (six autologous, one allogeneic).
      Primary induction with FLAG in elderly AML patients achieves a high remission
      rate without prohibitive mucosal or cardiac toxicity and may thus be considered
      as an alternative to standard anthracycline-based regimens in this setting.

PMID- 16303179
TI  - Additional Her 2/neu gene copies in patients with Sezary syndrome.
AB  - BACKGROUND: Her 2/neu gene amplification has been reported in several types of
      cancer. Monoclonal antibodies against the Her 2/neu receptor are used as a
      treatment in e.g. metastatic breast cancer. AIM: The aim of this study was to
      determine the frequency of additional Her 2/neu gene copies in relations to the
      number of chromosome 17 centromeres of patients with Sezary syndrome. METHODS:
      Fluorescence in situ hybridization (FISH) with probes specific for the Her 2/neu
      gene locus and the centromere of chromosome 17 was performed on nuclei from
      peripheral blood cells of 9 patients with Sezary syndrome. For analysis of Her
      2/neu protein expression immunostaining was performed. In addition, FISH was used
      to analyze distribution of typical lymphocytes on cryo-cut sections of affected
      skin of two patients. RESULTS: 7/9 cases showed additional Her 2/neu gene copies
      in relation to the number of chromosome 17 centromeres. 4/5 cases with additional
      Her 2/neu gene copies in which immunostaining was performed expressed Her 2/neu
      protein. On cryo-cut sections atypical lymphocytes with additional Her 2/neu gene
      copies were detected in the dermis as well as in the epidermis of affected skin.
      DISCUSSION: These data suggest that Her 2/neu might be involved in the
      pathogenesis of Sezary syndrome and that Her 2/neu might be a promising target
      for antitumor therapy in a subgroup of patients.

PMID- 16303180
TI  - ELF4 is fused to ERG in a case of acute myeloid leukemia with a t(X;21)(q25
      26;q22).
AB  - We report a novel chromosomal translocation in AML, t(X;21)(q25-26;q22),
      resulting in a fusion transcript between two ETS domain family members, ELF4 (at
      Xq25) and ERG (at 21q22). ERG has been associated previously with other fusion
      partners, specifically FUS and EWSR1, and implicated in both AML and Ewing's
      sarcoma. RT-PCR analysis of RNA isolated from bone marrow samples from the
      patient demonstrates that the translocation occurs within intron 1 of ERG isoform
      1 (ERG-1) and intron 2 of ELF4 resulting in an in-frame fusion joining exon 2
      from ELF4 with exon 2 of ERG. This is the first reported case of an ELF4-ERG
      fusion and identification of the specific ERG exon involved in the fusion that
      differentiates ERG isoforms. In addition, this case also directly implicates a
      new role for ELF4 in cancer.

PMID- 16303181
TI  - TCR gamma chain diversity in the spleen of the duckbill platypus (Ornithorhynchus
      anatinus).
AB  - TCR gamma (TRG) chain diversity in splenic gammadelta T cells was determined for
      an egg-laying mammal (or monotreme), the duckbill platypus. Three distinct V
      subgroups were found in the expressed TRG chains and these three subgroups are
      members of a clade not found so far in eutherian mammals or birds. Each subgroup
      contains approximately five V gene segments, and their overall divergence is much
      less than is found in eutherians and birds, consistent with their recent
      evolution from an ancestral V gene segment. The platypus TRG locus also contains
      three C region genes and many of the residues involved in TCR function, such as
      interactions with CD3, were conserved in the monotreme C regions. All non
      eutherian mammals (monotremes and marsupials) lacked the second cysteine residue
      necessary to form the intradomain disulfide bond in the C region, a loss
      apparently due to independent mutations in marsupials and monotremes. Monotreme
      TRGC regions also had among the most variation in the length of the connecting
      peptide region described for any species due to repeated motifs.

PMID- 16303182
TI  - Treating the vulnerable in England and Wales: the impact of law reform and
      changing policy.
AB  - This article considers the role of treatment in the provision of mental health
      care in England and Wales. The current legislative position with regard to the
      making of treatment choices following compulsory commitment will be examined.
      Consideration will also be given to the position of the informal hospitalised
      patient, as in the case of R v. Bournewood Community and Mental Health NHS Trust,
      ex parte L and finally, the role of the common law in establishing (in)capacity
      in relation to the non-consensual provision of treatment for physical conditions.
      Attention will then be given to the reform process, which is currently ongoing in
      England and Wales, and its likely impact on treatment provision. The Mental
      Capacity Act 2005 received Royal Assent on the 7th April 2005, while the draft
      Mental Health Bill 2004 underwent detailed examination by the Joint Scrutiny
      Committee, a report of which was published on the 23rd March 2005. On the 13th
      July 2005 the British Government outlined its response following the publication
      of the Scrutiny Committee's recommendations and despite it accepting many of the
      recommendations put forward, some significant areas of concern remain making the
      draft Mental Health Bill 2004 "a long way from acceptable legislation".

PMID- 16303183
TI  - Gene expression of the constant region of the heavy chain of immunoglobulin G
      (IgG CRHC) is down-regulated in human decidua in association with preeclampsia.
AB  - An aberrant interaction at the maternal/fetal interface between the genetically
      distinct fetal trophoblast cells and cells of the maternal decidua has been
      proposed as an initiating factor in one of the major complications of human
      pregnancy, preeclampsia. Biochemical and epidemiological studies suggest that the
      immune system plays an important role in preeclampsia. Thus, the aim of this
      study was to determine the decidual gene expression status in preeclampsia of one
      of the key components of the adaptive immune system. Total RNA was extracted from
      decidua collected from women with normal pregnancies and those complicated by
      preeclampsia. Reverse Northern analysis was performed on 72 cDNAs from human
      decidua and differentially expressed genes identified were analysed further using
      semi-quantitative RT-PCR and Northern blot analysis. Expression of the gene
      encoding the constant region of the heavy chain of immunoglobulin G (IgG CRHC)
      was shown to be down-regulated in association with preeclampsia. These data
      support the hypothesis that immune maladaptation may play an important role in
      the pathogenesis of preeclampsia.

PMID- 16303185
TI  - Influence of reactivity to novelty and anxiety on hypothalamic-pituitary-adrenal
      and prolactin responses to two different novel environments in adult male rats.
AB  - Since stressor-induced activation of the hypothalamic-pituitary-adrenal (HPA)
      axis is involved in some stress-related pathologies, much attention has been paid
      in laboratory animals to the study of the relationship between endocrine,
      particularly HPA, responsiveness to stressors and other individual
      characteristics, such as reactivity to novelty and fear/anxiety. In the present
      study, adult male rats were classified as high or low reactive to novelty (HR
      versus LR), as a function of the horizontal activity displayed during 30 min in a
      circular corridor, and as high or low anxiety (HA versus LA) as a function of the
      time spent in the open arms of the elevated plus-maze. Then, the behavioural and
      hormonal response to two distinct novel environments (the hole-board and the
      light-dark) was assessed in the same subjects, using a counterbalanced design.
      Plasma prolactin, ACTH and corticosterone responses to the hole-board were higher
      than to the light-dark, a good correlation between the two tests being found for
      each hormone. Whereas the hormonal response to the novel environments was not
      affected by anxiety, HR rats showed a consistently higher HPA response than LR
      rats when the criteria to classify the animals were the activity during the first
      15 min in the circular corridor, but not when the activity during the second 15
      min was considered. Neither trait affected prolactin response. The present
      results demonstrate a good within-individual consistency of the endocrine
      response to novel environments and support the hypothesis of a higher HPA
      response to stressors for HR versus LR rats. In contrast, no contribution of
      fear/anxiety to endocrine responsiveness was observed.

PMID- 16303184
TI  - 9-Cis-retinoic acid suppresses inflammatory responses of microglia and
      astrocytes.
AB  - Retinoic acid (RA) regulates a wide range of biologic process, including
      inflammation. Previously, RA was shown to inhibit the clinical signs of
      experimental autoimmune encephalomyelitis (EAE), an animal model of multiple
      sclerosis (MS). The current study investigated the effects of 9-cis-RA on primary
      mouse microglia and astrocytes, two cell types implicated in the pathology of MS
      and EAE. The studies demonstrated that 9-cis-RA inhibited the production of
      nitric oxide (NO) as well as the pro-inflammatory cytokines TNF-alpha, IL-1beta
      and IL-12 p40 by LPS-stimulated microglia. However, this retinoid had no effect
      on IL-6 secretion and increased MCP-1 production by LPS-stimulated microglia. In
      LPS-stimulated astrocytes, 9-cis-RA inhibited NO and TNF-alpha production but had
      not effect on IL-1beta, IL-6 and MCP-1 secretion. These results suggest that RA
      modulates EAE, at least in part, by suppressing the production of NO and specific
      inflammatory cytokines from activated glia and suggests that RA might be
      effective in the treatment of MS.

PMID- 16303186
TI  - Differential involvement of 5-HT projections within the amygdala in prepulse
      inhibition but not in psychotomimetic drug-induced hyperlocomotion.
AB  - While there is abundant evidence for a role of 5-HT and the amygdala in anxiety
      and depression, the role of 5-HT in this brain region in schizophrenia is less
      well understood. We therefore examined the effects of local 5-HT depletion in the
      amygdala on psychotomimetic drug-induced locomotor hyperactivity and prepulse
      inhibition, two animal model of aspects of schizophrenia. Pentobarbital
      anaesthetized (60 mg/kg, i.p.) male Sprague-Dawley rats were stereotaxically
      micro-injected with 0.5 microl of a 5 microg/mul solution of the 5-HT neurotoxin
      5,7-dihydroxytryptamine (5,7-DHT) into either the basolateral (BLA) or central
      nucleus of amygdala (CeN). Two weeks after the surgery, rats with BLA lesions did
      not show changes in either psychotomimetic drug-induced locomotor hyperactivity
      or prepulse inhibition. In contrast, rats with CeN lesions showed significant
      disruption of prepulse inhibition, but no changes in psychotomimetic drug-induced
      locomotor hyperactivity. Neurochemical analysis and autoradiographic labelling of
      5-HT transporter sites showed that a good degree of anatomical selectivity was
      obtained. Following administration of 5,7-DHT into the amygdala, the
      concentration of 5-HT was significantly reduced. Similarly, 5-HT transporter
      autoradiographs showed differential and selective lesions of 5-HT innervation in
      targeted subregions of the amygdala. These results provide evidence for
      differential involvement of 5-HT projections within the amygdala in prepulse
      inhibition but not locomotor hyperactivity. Thus, the present study supports the
      view that 5-HT in the amygdala may be involved in aspects of schizophrenia and a
      target for antipsychotic drug action.

PMID- 16303188
TI  - MDCT detection of congenital absence of the left circumflex artery associated
      with atherosclerotic coronary artery disease.

PMID- 16303187
TI  - Identification and molecular cloning of the Neospora caninum SAG4 gene
      specifically expressed at bradyzoite stage.
AB  - Here, we identify and clone the NcSAG4 gene, orthologue to the Toxoplasma gondii
      TgSAG4 gene, and the first reported gene to be expressed specifically during the
      Neospora caninum bradyzoite stage. To isolate NcSAG4, we designed degenerate
      oligonucleotides based on the TgSAG4 protein amino acid sequence. A 312-bp DNA
      fragment was amplified by PCR from N. caninum genomic DNA, whose sequence showed
      65% identity to TgSAG4 gene over 257 bp. NcSAG4 gene sequence was obtained by PCR
      genome walking. Nucleotide sequencing of amplified DNA fragments showed a single
      uninterrupted 522-bp ORF that encoded a 173-amino-acid protein with a predicted
      molecular mass of 18,394 Da, with 69% similarity to the TgSAG4 antigen. A 28
      residue putative signal peptide was found at the NH2-terminus, followed by a
      strongly hydrophilic region. An amino acid motif for a phosphatidylinositol
      glycan anchor was identified at the COOH-terminus. The NcSAG4 protein lacking the
      putative signal peptide at the NH2-terminus was expressed in Escherichia coli and
      was recognized in western blot by sera from congenitally infected cattle. A mouse
      polyclonal anti-rNcSAG4 serum was produced for immunofluorescence studies, and
      revealed stage-specific NcSAG4 antigen expression in in vitro-cultured
      bradyzoites. Real-time reverse transcription-PCR analysis with samples from in
      vitro stage-conversion assay showed increasing levels of NcSAG4 transcript over
      time, suggesting a developmental upregulation of this gene.

PMID- 16303189
TI  - Surgical validation of real-time transthoracic 3D echocardiographic assessment of
      atrioventricular septal defects.
AB  - BACKGROUND: The purpose of this study was to evaluate the accuracy of AV valve
      morphology assessed by real-time transthoracic 3D echocardiography (RT-3DE)
      compared to surgical findings and to assess whether RT-3DE is applicable in
      clinical practice. METHODS: Between June 2004 to May 2005, 19 patients with an
      atrioventricular septal defect (AVSD) undergoing surgical treatment at our
      institution were enrolled in the study. RT-3DE was performed with Philips Sonos
      7500 echo-system and off-line analysis with TomTec Echoview software. The AVSD
      was assessed for the morphology of AV valve, with particular interest to the
      superior and inferior bridging leaflets. 3D data were compared with measurements
      and descriptions acquired during the surgical procedure. RESULTS: Acquisition of
      RT-3DE datasets was feasible in all patients. Of the 19 patients, there were 11
      infants (age <1 year). The duration of 3D data acquisition was 12+/-3 min for
      patients above 1 year and 4+/-2 for infants. Reconstruction time was 22+/-8 min.
      In all patients the AV valve orifice and RT-3DE observations of the superior and
      inferior bridging leaflets were all correctly identified by RT-3DE compared with
      the surgical findings. CONCLUSION: Real-time transthoracic 3D echocardiography
      provides accurate assessment of AVSDs and correctly depicts the AV valve
      morphology. After a short learning curve, RT-3DE is easily applicable during
      daily clinical practice.

PMID- 16303190
TI  - Circumstances and mode of in-hospital death in 5750 consecutive patients
      undergoing percutaneous transluminal coronary angioplasty.

PMID- 16303191
TI  - Comprehensive coronary risk determination in primary prevention: an imaging and
      clinical based definition combining computed tomographic coronary artery calcium
      score and national cholesterol education program risk score.
AB  - Cardiovascular disease (CVD) is the leading cause of mortality and a major cause
      of morbidity. Coronary heart disease (CHD) accounts for nearly half of all CVD
      deaths. Currently estimation of risk in primary prevention is based on the
      Framingham risk equations, which inputs traditional risk factors and is helpful
      in predicting the development of CHD in asymptomatic individuals. However many
      individuals suffer events in the absence of established risk factors for
      atherosclerosis and broad based population risk estimations may have little
      precision when applied to a given individual. To meet the challenge of CHD risk
      assessment, several tools have been developed to identify atherosclerotic disease
      in its preclinical stages. This paper aims to incorporate information from
      coronary artery calcification (CAC) scoring from a computed tomographic
      "heartscan" (using Electron Beam Tomography (EBT) as the validated prototype)
      along with current Framingham risk profiling in order to refine risk on an
      absolute scale by combining imaging and clinical data to affect a more
      comprehensive calculation of absolute risk in a given individual. For CAC scores
      above the 75th percentile but <90th percentile, 10 years is added to
      chronological age, and for CAC scores above the 90th percentile, 20 years is
      added to current chronological age. Among those in whom a positive CAC score is
      the norm such as older individuals (men> or =55 years, women> or =65 years) a CAC
      = 0 will result in an age point score corresponding to the age-group whose median
      CAC score is zero i.e., 40-44 years for men and 55-59 years for women. The
      utilization of CAC scores allows the inclusion of sub-clinical disease definition
      into the context of modifiable risk factors as well as identifies high-risk
      individuals requiring aggressive treatment.

PMID- 16303192
TI  - Bumpversion vs. thumpversion.

PMID- 16303193
TI  - Time-course of cardiac remodeling following transcatheter closure of atrial
      septal defect.
AB  - BACKGROUND: Right chamber dilatation and right-to-left volumetric unbalance are
      well-known cardiac consequences of atrial septal defect (ASD) shunt, accounting
      for most of its long-term complications. Thus, cardiac volumetric unloading is a
      major aim of ASD closure. Different from surgery, transcatheter option might be
      considered as an "unbiased" tool to evaluate the cardiac geometric remodeling
      following ASD closure. METHODS: Extent and time-course of cardiac geometric
      changes were assessed by echocardiography 24 h, 1 and 6 months after percutaneous
      closure of large ASD (mean diameter 17+/-6 mm, QP/QS 2.2+/-0.9) in 42
      asymptomatic patients (age 22+/-18 years). RESULTS: Transcatheter closure was
      accomplished using the Amplatzer Septal Occluder device (mean 23+/-7 mm, median
      24 mm), achieving a complete occlusion in all patients at the 6-month follow-up
      control. After ASD closure, right atrial (RA) volume reduced from 45+/-24 to 28+/
      12 ml (-37.8%, p<0.001), while left atrial (LA) volume did not significantly
      change. Inlet and infundibulum right ventricular (RV) end-diastolic diameters
      reduced by 23+/-2% and 23+/-3%, respectively (p<0.001 for both measurements),
      although with a different time-course of changes. Finally, transverse left
      ventricular (LV) end-diastolic diameter increased from 39+/-7 to 44+/-5 mm
      (+11.4%, p<0.01). These geometric changes resulted in an RV/LV diameter ratio
      decrease by 34+/-3% (p<0.001). Nearly 90% of cardiac remodeling ensued within 1
      month from shunt disappearance (50% within 24 h). CONCLUSIONS: Percutaneous ASD
      closure results in early and striking cardiac geometric changes that almost
      completely revert the right-to-left volumetric unbalance. Most of this geometric
      remodeling ensues within a few weeks from ASD closure.

PMID- 16303194
TI  - Directional atherectomy before stenting versus stenting alone in percutaneous
      coronary interventions: a meta-analysis.
AB  - Plaque debulking before stenting is still controversial. We performed a meta
      analysis of 12 randomized and non-randomized trials comparing directional
      coronary atherectomy (DCA) before stenting versus stenting alone. Angiographic
      end points were acute gain, late loss and angiographic restenosis rate. Clinical
      end points were early major adverse cardiac events [MACEs: death, Q-wave
      myocardial infarction (MI), non-Q-wave MI], late MACEs (death, Q-wave MI) and
      target lesion revascularization (TLR). Data are expressed as odds ratio (OR) with
      95% confidence intervals (CI) or weighted mean difference (WMD) with 95% CI, as
      appropriate. A total of 1216 patients undergoing DCA before stent and 1484
      patients undergoing stent alone have been included. DCA before stent was
      associated to a better acute gain compared to stenting alone (WMD 0.23, [0.18
      0.28]; p<0.0001), to a striking reduction of angiographic restenosis rate (OR of
      0.67, [0.54-0.84], p=0.0003) and to a significantly lower rate of late TLR (OR
      0.73 [0.59-0.91], p=0.006). Late loss did not differ between the two groups (WMD
      0.00 [-0.08 and 0.08], p=0.98). We found a higher rate of early MACEs for the
      combined approach (OR 1.87 [1.16-3.02], p=0.01), with similar prevalence of late
      MACEs (OR 0.83 [0.65-1.06], p=0.13). In conclusion, this meta-analysis
      demonstrates that DCA before stenting is superior to stenting alone with regard
      to acute angiographic results and TLR with a similar prevalence of late MACEs.
      The higher prevalence of early MACEs with DCA before stenting, however, is
      disturbing and probably related to distal embolization.

PMID- 16303195
TI  - Stakeholder position paper: poultry.
AB  - There has been renewed concern in recent years about the use of antibiotics in
      food animal production and the potential risk it may pose to public health due to
      transfer of antibiotic resistance factors via the food supply. Although a
      legitimate concern, it bears reminding that this debate is not new. It has been
      ongoing for decades, yet there is still no documented case of human treatment
      failure due to antibiotic resistant bacteria acquired from USDA-inspected meat
      and poultry. This fact strongly suggests that the issue is not the imminent
      threat as has been portrayed by certain individuals or advocacy groups. The
      poultry industry as a whole has been using antibiotics responsibly for several
      decades, and there are strong beneficial arguments for their continued use.
      Responsible public policy demands a science-based approach be utilized in the
      decision making process before attempting to restrict or remove certain products
      due to overestimated risks. Part of this scientific review should include
      antibiotic use data, however this information has definite limitations and
      shortcomings which need to be understood before attempting to make any valid
      antibiotic resistance associations.

PMID- 16303196
TI  - Does trade affect child health?
AB  - Frankel and Romer [Frankel, J., Romer, D., 1999. Does trade cause growth?
      American Economic Review 89 (3), 379-399] documented positive effects of
      geographically determined trade openness on economic growth. At the same time,
      critics fear that openness can lead to a "race to the bottom" that increases
      pollution and reduces government resources for investments in health and
      education. We use Frankel and Romer's gravity model of trade to examine how
      openness to trade affects children. Overall, we find little harm from trade, and
      potential benefits largely through slightly faster GDP growth.

PMID- 16303197
TI  - Dynamics of boar semen motility inhibition as a semi-quantitative measurement of
      Bacillus cereus emetic toxin (Cereulide).
AB  - Qualitative and quantitative application of a computer assisted sperm analyzer
      (CASA) for detection and quantification of cereulide was described. The plot of
      the decrease of the percentage of boar semen progressive motility (PMOT%) in
      function of time and the visual inspection of curves provided a qualitative
      comparison between different samples (curve slope corresponds to the amount of
      cereulide in the sample). If the change of PMOT% over a time required for
      achieving PMOT% drop to 10% (DeltaPMOT%/Deltatau) is plotted against the standard
      curve (obtained with known concentrations of valinomycin), a semi-quantitative
      estimation of the amount of cereulide in the sample is obtained. An optimized
      CASA method was applied to determine the production of cereulide under different
      conditions. No cereulide was found in aerated samples and in samples incubated at
      12 degrees C. The amount of cereulide produced depended on the agar medium used,
      type of Bacillus cereus strain and the amount of oxygen present in the
      atmosphere.

PMID- 16303198
TI  - In vivo function of Rnd2 in the development of neocortical pyramidal neurons.
AB  - The present study examined the in vivo role of Rnd2, a Rho family small GTPase,
      in brain development. Rnd2 was expressed by radially migrating cells, which
      primarily develop to pyramidal neurons, during their stay in the subventricular
      zone of embryonic cerebral cortex and hippocampus. Exogenous expression of wild
      type and a constitutively active Rnd2, but not a negative mutant of Rnd2, in
      radially migrating cells by in utero electroporation disturbed their morphology
      and migration to upper layers. These results indicate that Rnd2 functions in vivo
      as a regulator of the migration and morphological changes associated with the
      development of pyramidal neurons.

PMID- 16303199
TI  - Modeling the survival of Salmonella spp. in chorizos.
AB  - The survival of Salmonella spp. in chorizos has been studied under the effect of
      storage conditions; namely temperature (T=6, 25, 30 degrees C), air inflow
      velocity (F=0, 28.4 m/min), and initial water activity (a(w0)=0.85, 0.90, 0.93,
      0.95, 0.97). The pH was held at 5.0. A total of 20 survival curves were
      experimentally obtained at various combinations of operating conditions. The
      chorizos were stored under four conditions: in the refrigerator (Ref: T=6 degrees
      C, F=0 m/min), at room temperature (RT: T=25 degrees C, F=0 m/min), in the hood
      (Hd: T=25 degrees C, F=28.4 m/min), and in the incubator (Inc: T=30 degrees C,
      F=0 m/min). Semi-logarithmic plots of counts vs. time revealed nonlinear trends
      for all the survival curves, indicating that the first-order kinetics model
      (exponential distribution function) was not suitable. The Weibull cumulative
      distribution function, for which the exponential function is only a special case,
      was selected and used to model the survival curves. The Weibull model was fitted
      to the 20 curves and the model parameters (alpha and beta) were determined. The
      fitted survival curves agreed with the experimental data with R(2)=0.951, 0.969,
      0.908, and 0.871 for the Ref, RT, Hd, and Inc curves, respectively. Regression
      models relating alpha and beta to T, F, and a(w0) resulted in R(2) values of
      0.975 for alpha and 0.988 for beta. The alpha and beta models can be used to
      generate a survival curve for Salmonella in chorizos for a given set of operating
      conditions. Additionally, alpha and beta can be used to determine the times
      needed to reduce the count by 1 or 2 logs t(1D) and t(2D). It is concluded that
      the Weibull cumulative distribution function offers a powerful model for
      describing microbial survival data. A comparison with the pathogen modeling
      program (PMP) revealed that the survival kinetics of Salmonella spp. in chorizos
      could not be adequately predicted using PMP which underestimated the t(1D) and
      t(2D). The mean of the Weibull probability density function correlated strongly
      with t(1D) and t(2D), and can serve as an alternative to the D-values normally
      used with first-order kinetic models. Parametric studies were conducted and
      sensitivity of survival to operating conditions was evaluated and discussed in
      the paper. The models derived herein provide a means for the development of a
      reliable risk assessment system for controlling Salmonella spp. in chorizos.

PMID- 16303200
TI  - The molecular epidemiology of rabies associated with chiropteran hosts in Mexico.
AB  - While large-scale dog vaccination campaigns have significantly reduced urban
      rabies throughout Mexico, reports of sylvatic rabies, including cases of spill
      over of bat strains into livestock and humans, are increasing. To improve
      knowledge of these epidemiological trends, 64 Mexican rabies virus isolates from
      various host species, have been characterized. Phylogenetic analysis at the viral
      P locus identified distinct viral strains associated with terrestrial reservoirs
      (dog, skunk and fox/bobcat) and a variant associated with the insectivorous bat,
      T. brasiliensis, consistent with prior reports. Of the two distinct clades of
      viruses associated with the vampire bat reservoir, one comprised just four
      specimens and formed an outlying group to all other vampire bat rabies isolates
      including those from South America and the Caribbean, a finding consistent with
      the early emergence of the vampire bat reservoir in Mexico. Antigenic variation
      of the vampire bat specimens did not correlate with the main genetic groupings;
      moreover complete N gene sequence analysis of selected specimens indicated
      limited variation within the encoded nucleoprotein that could form the basis of
      antigenic variation. A single isolate recovered from a cat represents a new viral
      variant not previously identified in North America that probably circulates in a
      species of insectivorous bat.

PMID- 16303201
TI  - Translational control by viral proteinases.
AB  - Most RNA viruses have evolved strategies to regulate cellular translation in
      order to promote preferential expression of the viral genome. Positive strand RNA
      viruses express large portions, or all of their proteome via translation of large
      polyproteins that are processed by embedded viral proteinases or host
      proteinases. Several of these viral proteinases are known to interact with host
      proteins, particularly with the host translation machinery, and thus, encompass
      the dual functions of processing of viral polyproteins and exerting translation
      control. Picornaviruses are perhaps the best characterized in regards to
      interaction of their proteinases with the host translation machinery and will be
      emphasized here. However, new findings have shown that similar paradigms exist in
      other viral systems which will be discussed.

PMID- 16303202
TI  - Structural optimization of a "smart" doxorubicin-polypeptide conjugate for
      thermally targeted delivery to solid tumors.
AB  - A thermoresponsive, genetically engineered, elastin-like polypeptide (ELP)
      containing a C-terminal cysteine residue was synthesized and purified by inverse
      transition cycling (ITC) and conjugated to doxorubicin (Dox) molecules through
      four different pH-sensitive, maleimide-activated, hydrazone linkers. The
      efficiency of Dox activation, conjugation ratios to ELP and biophysical
      characterization-hydrodynamic radius (Rh) and the temperature transition kinetics
      of the ELP-Dox conjugates and pH-mediated release of Dox were quantified in this
      study. Conjugation ratios of the maleimide-activated Dox to the thiol group of a
      unique cysteine in the ELP were close to unity. The Rh of the conjugate increased
      as the linker length between the ELP backbone and Dox was increased. The linker
      structure and length had little effect on the Tt of the ELP-Dox conjugates, as
      all conjugates exhibited Tt's that were similar to the native ELP. However, the
      ELP-Dox conjugates with longer linkers exhibited slower transition kinetics
      compared to the ELP-Dox conjugates with shorter linkers. The highest release of
      the ELP-Dox conjugate by cleavage of the hydrazone bond at pH 4 was nearly 80%
      over 72 h and was exhibited by the conjugate with the shortest linker.

PMID- 16303203
TI  - Normative values of carotid artery intima-media thickness in healthy Korean
      adults and estimation of macrovascular diseases relative risk using this data in
      type 2 diabetes patients.
AB  - The objectives of this study were to determine normative values of carotid intima
      media thickness (IMT) in healthy Korean subjects and to use these values to
      estimate the relative risk of macrovascular diseases in patients with type 2
      diabetes mellitus (T2DM). High-resolution B-mode ultrasonography was performed in
      1,229 healthy subjects and 830 T2DM patients. Height, weight, blood pressure,
      fasting plasma glucose, total cholesterol, triglyceride, HDL-cholesterol, LDL
      cholesterol, and fasting insulin level were measured. Subjects were classified as
      healthy subjects; T2DM patients without ischemic heart disease (IHD), stroke, and
      peripheral arterial occlusive diseases (PAOD); T2DM patients with IHD, stroke, or
      PAOD. IMT was significantly increased as age increased. Patients with T2DM had
      higher IMTs compared to healthy subjects. Independent risk factors of IMT were
      age, systolic blood pressure, BMI for healthy subjects, and age, duration of
      diabetes, LDL-cholesterol for T2DM subjects. According to presence of increased
      IMT, the relative risks of IHD, stroke, and PAOD in diabetic subjects, were 2.34
      (CI; 1.32-4.14), 2.95 (CI; 1.46-5.54), and 3.64 (CI; 1.66-7.40), respectively.
      This study suggests normative values that can be used as an index for carotid
      artery IMT of healthy Korean subjects, and that IMT data reflects the risk of
      macrovascular diseases in T2DM.

PMID- 16303204
TI  - Priority setting of public spending in developing countries: do not try to do
      everything for everybody.
AB  - BACKGROUND: Public spending on health care in many developing countries falls
      short to provide a comprehensive set of essential health services, which
      indicates the need to target and prioritize resources. However, governments often
      attempt to provide free services to the whole population, and often spend
      resources on low-impact services. This results in an inequitable and inefficient
      use of resources. METHODS: This paper presents a rational approach to targeting
      and prioritization of public spending, with an application to Ghana. First,
      interventions were tested against the economic justification for public funding,
      to define to whom spending should be targeted. Second, resulting interventions
      were prioritized on the basis of medical and non-medical criteria. RESULTS: The
      step-wise approach led to a rank ordering of interventions with a specification
      whether public spending should be targeted at the whole population or the poor
      only. Disease control priorities are prevention of mother-to-child HIV/AIDS
      transmission and oral rehydration therapy to treat diarrhea in childhood, and
      public funding of these interventions is warranted for the whole population. Case
      management of pneumonia in childhood is also a priority but public funding should
      be targeted at the poor only. Low priorities for public funding are certain
      interventions to control blood pressure, tobacco and alcohol abuse, be it for the
      whole population or the poor only. CONCLUSION: Governments should not try to
      provide everything for everybody. This may help health systems to move towards a
      more equitable and efficient use of resources.

PMID- 16303205
TI  - A method for calculation of arterial acid-base and blood gas status from
      measurements in the peripheral venous blood.
AB  - In non-emergency medical departments such as internal medicine sampling of
      arterial blood and analysis for acid-base status is not routinely performed.
      Peripheral venous blood is routinely taken but interpretation of its acid-base
      status is difficult. This paper presents a method for calculation of arterial
      acid-base and blood gas status from measurements in peripheral venous blood
      combined with a pulse oximeter measurement of arterial saturation. The use of the
      method has been illustrated using the data of three patients with different acid
      base, haemodynamic, and metabolic conditions. The sensitivity of the method has
      been tested for measurement errors including venous blood acid-base and blood gas
      status and pulse oximetry; errors due to physiological assumptions including the
      values of RQ and strong acid production at the tissues; and errors due to air
      bubbles in the blood. Errors due to these effects are relatively insignificant
      except for errors in calculated arterial PO(2), particularly when SpO(2) is
      greater than 97%; and errors when the change in base excess across the sampling
      site due to strong acid production is greater that 1.3 mmol/l.

PMID- 16303206
TI  - Vertebral axial rotation measurement method.
AB  - This study presents a new method for measuring axial rotation of vertebra.
      Anatomical landmarks of the vertebral body were first recognized in X-ray film.
      By employing appropriate geometrical relationships, vertebral body shape
      parameters and a computer iteration method, the rotation angle of vertebra on the
      transverse plane can rapidly be obtained. A cadaver lumbar spine axial rotation
      fixation device was designed to confirm the accuracy of the proposed methodology.
      Rotation angles on CT images were adopted as the golden standard and compared
      with analytical results based on X-ray films. Analytical results demonstrated
      that the proposed method obtained more accurate and reliable results than
      previous methods.

PMID- 16303208
TI  - Modelling the migration of contaminants through variably saturated dual-porosity,
      dual-permeability chalk.
AB  - In the Hesbaye region in Belgium, tracer tests performed in variably saturated
      fissured chalk rocks presented very contrasting results in terms of transit
      times, according to artificially controlled water recharge conditions prevailing
      during the experiments. Under intense recharge conditions, tracers migrated
      across the partially or fully saturated fissure network, at high velocity in
      accordance with the high hydraulic conductivity and low effective porosity
      (fracture porosity). At the same time, a portion of the tracer was temporarily
      retarded in the almost immobile water located in the matrix. Under natural
      infiltration conditions, the fissure network remained inactive. Tracers migrated
      downward through the matrix, at low velocity in relation with the low hydraulic
      conductivity and the large porosity of the matrix. Based on these observations,
      Brouyere et al. (2004a) [Brouyere, S., Dassargues, A., Hallet, V., 2004a.
      Migration of contaminants through the unsaturated zone overlying the Hesbaye
      chalky aquifer in Belgium: a field investigation, J. Contam. Hydrol., 72 (1-4),
      135-164, doi: 10.1016/j.conhyd.2003.10.009] proposed a conceptual model in order
      to explain the migration of solutes in variably saturated, dual-porosity, dual
      permeability chalk. Here, mathematical and numerical modelling of tracer and
      contaminant migration in variably saturated fissured chalk is presented,
      considering the aforementioned conceptual model. A new mathematical formulation
      is proposed to represent the unsaturated properties of the fissured chalk in a
      more dynamic and appropriate way. At the same time, the rock water content is
      partitioned between mobile and immobile water phases, as a function of the water
      saturation of the chalk rock. The groundwater flow and contaminant transport in
      the variably saturated chalk is solved using the control volume finite element
      method. Modelling the field tracer experiments performed in the variably
      saturated chalk shows the adequacy and usefulness of the new conceptual,
      mathematical and numerical model.

PMID- 16303209
TI  - Dip-angle influence on areal DNAPL recovery by co-solvent flooding with and
      without pre-flooding.
AB  - A two-dimensional (2D) laboratory model was used to study effects of gravity on
      areal recovery of a representative dense non-aqueous phase liquid (DNAPL)
      contaminant by an alcohol pre-flood and co-solvent flood in dipping aquifers.
      Recent studies have demonstrated that injection of alcohol and co-solvent
      solutions can be used to reduce in-situ the density of DNAPL globules and
      displace the contaminant from the source zone. However, contact with aqueous
      alcohol reduces interfacial tension and causes DNAPL swelling, thus facilitating
      risk of uncontrolled downward DNAPL migration. The 2D laboratory model was
      operated with constant background gradient flow and a DNAPL spill was simulated
      using tetrachloroethene (PCE). The spill was dispersed to a trapped, immobile PCE
      saturation by a water flood. Areal PCE recovery was studied using a double
      triangle well pattern to simulate a remediation scheme consisting of an alcohol
      pre-flood using aqueous isobutanol ( approximately 10% vol.) followed by a co
      solvent flood using a solution of ethylene glycol (65%) and 1-propanol (35%).
      Experiments were conducted with the 2D model oriented in the horizontal plane and
      compared to experiments at the 15 degrees and 30 degrees dip-angle orientations.
      Injection was applied either in the downward or upward direction of flow.
      Experimental results were compared to theoretical predictions for flood front
      stability and used to evaluate effects of gravity on areal PCE recovery.
      Sensitivity experiments were performed to evaluate effects of the alcohol pre
      flood on PCE areal recovery. For experiments conducted with the alcohol pre-flood
      and the 2D model oriented in the horizontal plane, results indicate that 89-93%
      of source zone PCE was recovered. With injection oriented downward, results
      indicate that areal PCE recovery was 70-77% for a 15 degrees dip angle and 57-59%
      for a 30 degrees dip angle. With injection oriented upward, results indicate that
      areal PCE recovery was 57-60% at the 30 degrees dip angle, which was similar to
      PCE recovery for injection in the downward flow direction. Lower areal PCE
      recovery at greater dip angles in either direction of flow was attributed to
      DNAPL swelling and migration, flood front instabilities and bypassing of the
      displaced fluid past the extraction wells during the alcohol pre-flood.
      Additional results demonstrate that the use of an alcohol pre-flood can be
      beneficial in improving DNAPL recovery in the horizontal orientation, but pre
      flooding may reduce areal recovery efficiency in dip-angle orientations. This
      study also demonstrates the use of theoretical perturbation (fingering) analysis
      in predicting NAPL recovery efficiency for flooding processes in remediating
      aquifers with dip angles.

PMID- 16303210
TI  - Ypt32p regulates the translocation of Chs3p from an internal pool to the plasma
      membrane.
AB  - The transport of the chitin synthase III, Chs3p, to the plasma membrane is
      temporally and spatially regulated. Chs3p is delivered to the plasma membrane at
      the beginning of the cell cycle, forming chitin rings, and at the end of the cell
      cycle, forming the primary septum. During the rest of the cell cycle, it is
      maintained in intracellular compartments, termed chitosomes that share
      characteristics with the late Golgi and the early endosomes. Chs5p and Chs6p are
      required for the cell cycle-dependent delivery of Chs3p to the cell surface, but
      the mechanisms underlying the temporal regulation are still unknown. The Rab
      proteins, Ypt31/32p, are required for exit of secretory vesicles from the late
      Golgi and for recycling of proteins between the late Golgi and early endosomes.
      Either gain of Ypt32p function, by overexpression, or loss-of-function mutations
      alter the localization of Chs3p-GFP. Moreover, cells overexpressing Ypt32p
      accumulate chitin at the cell surface independent of Chs5p. Overexpression of
      Ypt32p also disrupts the localization of the late Golgi protein Sec7. We propose
      that Ypt31/32p have a role in regulating the delivery of Chs3p to the plasma
      membrane and deposition of chitin at the cell surface.

PMID- 16303211
TI  - Structure-activity studies of new melanocortin peptides containing an aromatic
      amino acid at the N-terminal position.
AB  - Cyclic melanotropin peptides, designed with an aromatic amino acid substitution
      at the N-terminal position of the MT-II-type scaffold, were prepared by solid
      phase peptide synthesis and evaluated for their ability to bind to and activate
      human melanocortin-1, -3, -4, and -5 receptors. The structure-activity studies of
      these MT-II analogues have identified a selective antagonist at the hMC4R (H-Phe
      c[Asp-Pro-d-Nal(2')-Arg-Trp-Gly-Lys]-NH(2), pA(2)=8.7), a selective partial
      agonist at the hMC4R (H-d-Nal(2')-c[Asp-Pro-d-Phe-Arg-Trp-Gly-Lys]-NH(2),
      IC(50)=11nM, EC(50)=56nM), and a selective partial agonist at the hMC3R (H-d-Phe
      c[Asp-Pro-d-Phe-Arg-Trp-Lys]-NH(2), IC(50)=3.7nM, EC(50)=4.9nM). Aromatic amino
      acid substitution at the N-terminus in conjuction with the expansion of the 23
      membered cyclic lactam MT-II scaffold to a 26-membered scaffold by addition of a
      Gly residue in position 10 leads to melanotropin peptides with enhanced receptor
      selectivity.

PMID- 16303212
TI  - A tryptic hydrolysate from bovine milk alphaS1-casein improves sleep in rats
      subjected to chronic mild stress.
AB  - The putative effects of a tryptic bovine alphaS1-casein hydrolysate on stress
      induced sleep disorders were investigated and their possible link with typical
      blood stress parameters such as plasma corticosterone concentrations and
      glycaemia was assessed. Rats were subjected to chronic stress in the form of
      environmental disturbances, while receiving an oral administration of the alphaS1
      casein hydrolysate (CH). Chronic stress significantly reduced sleep duration in
      control rats during the first 2 days of the stress period, but stress-induced
      sleep disturbance was prevented in CH-treated rats. Indeed, CH administration
      allowed the maintenance of slow wave sleep (SWS) duration and even a slight
      increase in paradoxical sleep (PS) duration in treated rats. Results on plasma
      corticosterone concentrations and on glycemia values were inconclusive with
      respect to the implication of the HPA axis in this study. However, the protective
      effect of the alphaS1-casein hydrolysate on sleep during exposure to our chronic
      mild stress conditions may be mediated by modulation of the central adrenergic
      response.

PMID- 16303213
TI  - A role for cyclic nucleotide monophosphates in synaptic modulation by a crayfish
      neuropeptide.
AB  - DF2 (DRNFLRFamide), a FMRFamide-like peptide, has been shown to increase the
      amount of transmitter released at crayfish neuromuscular junctions. Here, we
      examined a possible role for the cyclic nucleotide monophosphates, cAMP and cGMP,
      in DF2's effects on synaptic transmission. The effects of DF2 on synaptic
      transmission were monitored by recording excitatory postsynaptic potentials
      (EPSPs) in the deep abdominal extensor muscles of the crayfish, Procambarus
      clarkii. A number of activators and inhibitors were used to determine whether or
      not cAMP, cGMP, protein kinase A (PKA) and protein kinase G (PKG) mediate the
      effect of this neuropeptide. Phosphodiesterase inhibitors, known to inhibit the
      breakdown of cAMP (IBMX) and/or cGMP (mdBAMQ), potentiate the effect of DF2 on
      synaptic transmission. Activators of PKA (Sp-cAMPS) and PKG (8-pCPT-cGMP)
      increase EPSP amplitude, mimicking the effects of DF2. Inhibitors of PKA (Rp
      cAMPS) and PKG (Rp-8-pCPT-cGMPS) each block a portion of the response to the
      peptide, and when applied together these two inhibitors completely block the
      response. Taken together, these results indicate that cyclic nucleotides and
      cyclic nucleotide-dependent protein kinases are necessary components of the
      pathway underlying modulation by this neuropeptide.

PMID- 16303214
TI  - Molecular characterization of attenuated Japanese encephalitis live vaccine
      strain ML-17.
AB  - The Japanese encephalitis (JE) zoonotic vaccine strain ML-17 was sequenced and
      compared to related JE virus strains to identify genomic attenuation markers.
      Relative to its parental strain, JaOH0566, 25 nucleotide alterations and 10 amino
      acid changes to, prM/M(2), NS2A(1), NS4B(3) and NS5(4) proteins were recorded.
      Both structural-gene changes were in the prM/M region (127Met-->Ile and 274Asn-
      >Thr). To study the effects of these prM/M changes, mutants bearing the changes
      were prepared using an infectious clone of JaOArS982 previously established at
      this lab. Compared with JaOArS982, mutant 127(Met-->Ile) showed marked reduction
      in murine neuroinvasiveness. Mutant 274(Asn-->Thr), showed slight reduction.
      Neither mutant recorded ML-17-equivalent attenuation, implying that prM/M changes
      need to combine with other recorded genomic differences to cause attenuation.
      Importantly, ML-17 with its unchanged E region, presents a possible backbone
      candidate for preparation of "E-replacement" type live attenuated flavivirus
      chimeric vaccines.

PMID- 16303215
TI  - Safety and immunogenicity of a Proteosome -trivalent inactivated influenza
      vaccine, given nasally to healthy adults.
AB  - We studied the safety and immunogenicity of a nasally administered vaccine
      comprising three monovalent inactivated influenza antigens (A/New Caledonia/20/99
      (H1N1), A/Panama/2007/99 (H3N2), and B/Guangdong/120/2000) non-covalently
      associated with outer membrane proteins of Neisseria meningitidis (Proteosome) in
      normal, healthy adults. In a randomized, double-blind trial participants (n = 78)
      were allocated to placebo or a single nasal dose of vaccine containing 15, 30, or
      45 microg of each of the three HA antigens, or two nasal doses containing 30
      microg of each HA, separated by 2 weeks. The vaccine was generally well tolerated
      in all doses tested, and in a one or two-dose schedule. A shallow vaccine
      reactogenicity dose-response was seen. The most common local reaction was nasal
      congestion, which occurred in up to 48.3% of vaccine recipients in days 0-6 after
      vaccine but was mild and self-limiting; this reaction was not significantly more
      common among active vaccine recipients than placebo recipients. Mild to moderate
      headache was the most commonly reported systemic reactogenicity complaint in all
      treatment groups, and was the only solicited complaint to increase significantly
      in frequency after a second active dose. No severe systemic reactions occurred. A
      positive and statistically significant antibody response was observed, in serum
      and in nasal secretions, to increasing dose for all three antigens. Serum HAI
      titre responses and nasal secretory IgA immune responses were elicited against
      all three antigens. Further testing of this nasal influenza vaccine is warranted
      to determine its safety and immunogenicity in these populations and its efficacy
      in the prevention of clinical illness.

PMID- 16303217
TI  - Immunogenicity of a recombinant, yeast-derived, anti-hepatitis-B vaccine after
      alternative dosage and schedule vaccination in Pakistani children.
AB  - A controlled, randomized trial was conducted in urban areas of Karachi and Lahore
      with the aim to look for ways to improve the cost-effectiveness of hepatitis B
      vaccination. Children under 15 years old (including neonates) were selected and
      screened for immunization by three regimens according to the frequency and doses
      of the recombinant vaccine used (Heberbiovac HB, Heber Biotec, Havana). Group A
      received 10 microg at 0, 1 months; group B (control) received 10 microg at 0, 1
      and 2 months (standard regime), and group C received 5 microg at 0, 1 and 2
      months. Antibody levels were titrated 2 months after the last dose. Cut-off for
      seroprotection and hyperresponse were taken as 10 and 100 IU/L, respectively.
      Nine hundred and ninety children were included and evaluated after discarding
      those positive for serological hepatitis virus infection markers. Seroprotection
      rates were 100, 99.7 and 99.7%, and hyperresponse was achieved by 92.7, 99.4, and
      97% of the vaccinees in groups A, B, and C, respectively. The same good result
      was obtained in extreme ages subgroups (< or =1 year and > or =10 years old). The
      1-year follow up of the children from Karachi showed good persistence of
      seroprotection (98, 100, and 99.4%) and hyperresponse (79.7, 96.7, and 87.4%). It
      is concluded that it is feasible to improve the cost-benefit ratio and compliance
      of hepatitis B vaccination by means of a two-shots or reduced dose schedule of
      the vaccine employed in the trial.

PMID- 16303216
TI  - Immunogenicity and safety of four different doses of Haemophilus influenzae type
      b-tetanus toxoid conjugated vaccine, combined with diphtheria-tetanus-pertussis
      vaccine (DTP-Hib), in Indonesian infants.
AB  - Widespread use of Haemophilus influenzae type b (Hib) conjugated vaccine in
      industrialized countries has resulted in a dramatic decline in the incidence of
      invasive Hib diseases, but the vaccine's cost has prevented its inclusion in
      basic immunization programs in developing countries. To overcome this problem,
      combination with diphtheria-tetanus-pertussis (DTP) vaccine or reduction in the
      dose of Hib vaccine has been proposed. To evaluate the immunogenicity and adverse
      reactions from lower doses of Hib-polyribosylphosphate (PRP) conjugated with
      tetanus toxoid (PRP-T), a double-blind study was conducted in Jakarta, Indonesia,
      and its suburbs. A total of 1048 infants 6 weeks to 6 months of age received
      three doses of DTP vaccine combined with the usual 10 microg dose or with a
      reduced dose of 5, 2.5 or 1.25 microg of PRP-T at two-monthly intervals.
      Antibodies were measured prior to the first dose and 4-6 weeks following the
      third dose. Adverse reactions were similar among all four groups. The only
      significant difference was a higher rate of irritability (p<0.02) and of
      temperature elevation >38 degrees C (p<0.009) after doses 1 and 2 in the lowest
      dose group (1.25 microg PRP-T) compared to the other groups. All participants
      tested had a 4-fold increase in antibodies against all DTP antigens. In addition,
      after a fourth booster dose of Hib, 99.6% of infants produced >or=0.15 microg/ml
      of antibody to Hib-PRP, and 96.4% showed levels >or=1.0 microg/ml after primary
      immunization, level that correlate with short- and long-term immunity,
      respectively. Antibody titers to the PRP antigen showed no significant
      differences among dosage groups with the exception of the 5.0 microg group, which
      had a significantly higher GMC than the 1.25 microg group (p<0.012). This study
      demonstrates that primary vaccination with half, one-fourth, or one-eighth of the
      usual dose of PRP-T, combined with DTP vaccine, produces protective immune
      responses, and has side effects that are comparable to DTP vaccination alone. In
      these lower dosages, PRP-T conjugate vaccine can lower vaccine costs to a level
      that is affordable for infant immunization programs in developing countries.

PMID- 16303218
TI  - Naturally occurring radioactive material (NORM) from a former phosphoric acid
      processing plant.
AB  - In recent years there has been an increasing awareness of the radiological impact
      of non-nuclear industries that extract and/or process ores and minerals
      containing naturally occurring radioactive material (NORM). These industrial
      activities may result in significant radioactive contamination of (by-) products,
      wastes and plant installations. In this study, scale samples were collected from
      a decommissioned phosphoric acid processing plant. To determine the nature and
      concentration of NORM retained in pipe-work and associated process plant, four
      main areas of the site were investigated: (1) the 'Green Acid Plant', where crude
      acid was concentrated; (2) the green acid storage tanks; (3) the Purified White
      Acid (PWA) plant, where inorganic impurities were removed; and (4) the solid
      waste, disposed of on-site as landfill. The scale samples predominantly comprise
      the following: fluorides (e.g. ralstonite); calcium sulphate (e.g. gypsum); and
      an assemblage of mixed fluorides and phosphates (e.g. iron fluoride hydrate,
      calcium phosphate), respectively. The radioactive inventory is dominated by 238U
      and its decay chain products, and significant fractionation along the series
      occurs. Compared to the feedstock ore, elevated concentrations (< or =8.8 Bq/g)
      of 238U were found to be retained in installations where the process stream was
      rich in fluorides and phosphates. In addition, enriched levels (< or =11 Bq/g) of
      226Ra were found in association with precipitates of calcium sulphate. Water
      extraction tests indicate that many of the scales and waste contain significantly
      soluble materials and readily release radioactivity into solution.

PMID- 16303219
TI  - Perfluorooctanesulfonate and related fluorochemicals in biological samples from
      the north coast of Colombia.
AB  - Perfluorinated compounds are widespread pollutants of toxicological importance
      that have been detected in environmental matrices. However, little is known on
      their distribution in South America. In this study, distribution of
      perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA),
      perfluorohexanesulfonate (PFHxS), and perfluorooctanesulfonamide (PFOSA) was
      determined in the bile of mullet, Mugil incilis, and in tissues of pelicans
      (Pelecanus occidentalis) collected from North Colombia. Analysis was performed by
      HPLC mass spectrometry after ion-pair extraction. PFOS was found in all bile
      samples and PFOA and PFHxS were detected at lower frequency. Average
      concentrations of PFOS, PFOA, and PFHxS in bile of fish from Cartagena Bay, an
      industrialized site, and Totumo marsh, a reference site, were 3673, 370, 489 and
      713, 47.4, 1.27 ng/mL, respectively. PFOS concentrations in pelican organs
      decreased in the order of spleen>liver>lung>kidney>brain>heart>muscle. These
      results suggest, for the first time, that perfluorinated compounds are also found
      in wildlife from Latin American countries.

PMID- 16303220
TI  - What do cancer support groups provide which other supportive relationships do
      not? The experience of peer support groups for people with cancer.
AB  - This qualitative study examined the questions of what cancer support groups
      provide that other supportive relationships do not, and what the self perceived
      consequences are of support group attendance. Nine representative Australian
      cancer peer support groups, consisting of a total of 93 interviewees, 75 women,
      and 18 men, with a mean age of 62, took part in participant observation and focus
      group interviews, with the data analysed using positioning theory. Support groups
      were positioned by participants as providing a unique sense of community,
      unconditional acceptance, and information about cancer and its treatment, in
      contrast to the isolation, rejection, and lack of knowledge about cancer
      frequently experienced outside the group. Groups were also positioned as
      occasionally emotionally challenging, in contrast to the experience of
      normalising support from family and friends. Increased empowerment and agency
      were positioned as the most significant consequences of group support, consisting
      of increased confidence and a sense of control in relation to self, living with
      cancer, and interactions with others, in particular the medical profession. The
      support group was also positioned as facilitating positive relationships with
      family and friends because of relieving their burden of care, by providing a safe
      space for the expression of emotion. No difference was found between
      professionally led and peer led support groups, suggesting that it is not the
      professional background of the leader which is of importance, but whether the
      group provides a supportive environment, mutuality, and a sense of belonging, and
      whether it meets the perceived needs of those attending. It is suggested that
      future research should examine the construction and experience of social support
      in those who drop out of, or who do not attend, cancer support groups, in order
      to provide further insight into the contrast between social support within groups
      and support in other contexts.

PMID- 16303221
TI  - The burden of disease associated with being African-American in the United States
      and the contribution of socio-economic status.
AB  - The burden of disease associated with being African-American in the US, and the
      contribution of socio-economic status (SES) to that burden have not been
      quantified. We derived burden of disease estimates for African-Americans and
      whites by age group, with and without adjustment for SES (income and education).
      We used (1) EQ-5D Index scores from the 2000 US Medical Expenditure Panel Survey
      to derive quality-adjusted life year (QALY) compatible estimates of health
      related quality of life (HRQL); (2) 1990-1992 US National Health Interview Survey
      data linked to National Death Index data through 1995 to derive mortality risks;
      and (3) 2000 US mortality data from the National Center for Health Statistics to
      derive current mortality estimates for the US population. We found that relative
      to whites, African-Americans suffer 67,000 more deaths annually, resulting in 2.2
      million years of life lost, and 1.1 million years after SES adjustment. Total
      QALYs lost (HRQL and mortality) dropped from 2.3 million to 902,000 after SES
      adjustment. SES differences between African-Americans and whites appear to
      explain all the HRQL disparity but only half the mortality disparity. Better
      understanding of the disparate effects of SES may inform interventions to address
      health disparities adversely affecting African-Americans.

PMID- 16303222
TI  - Female sex workers as health educators with men who buy sex: utilising narratives
      of rationalisations.
AB  - This paper reports on findings from an ethnographic study of female sex workers
      who work in the indoor sex markets in a British city. An unexpected finding was
      the collective narratives that sex workers construct to rationalise their
      involvement in the sex industry. Fifty-five respondents who took part in in-depth
      interviews maintained that prostitution is a useful occupation and function in
      society. Narratives included providing emotional support to male clients; a
      service for men who are socially or physically disabled; preventing men having
      adulterous affairs; and health education, disease prevention and as therapists
      for sexual dysfunction. This paper evaluates how the latter narrative of sexual
      health promotion is an example of how sex workers are ideally placed to work as
      health educators with men who buy sex. Arguing against gender specific sexual
      health policies, men who buy sex are described as a 'high risk' group who are
      also a hidden population. Limitations posed by ideological, ethical and practical
      concerns relating to the specific conditions of the sex industry suggest that
      this proposal could be partially successful. In conclusion, I suggest the sexual
      health of the nation and the place of sex workers in society must be considered
      with regard to recent policy debates on the management of prostitution and the
      cultural construction of the sex worker.

PMID- 16303223
TI  - Acute effects of tianeptine on circulating neurotransmitters and cardiovascular
      parameters.
AB  - Tianeptine is a serotonin-uptake enhancer drug whose antidepressant effectiveness
      is based on its ability to reduce rather than increase serotonin availability at
      the synaptic cleft. This paradoxical neuropharmacological mechanism has raised
      doubt among neuropharmacologists and psychiatrists as to the role of tianeptine
      as a trusty-reliable antidepressant drug. This controversial issue led us to
      investigate the acute effects of a single, oral dose (12.5 mg) of this drug on
      circulating neurotransmitters and cardiovascular parameters in 50 healthy
      subjects. The drug provoked a striking and significant reduction of plasma
      noradrenaline (NA) and plasma serotonin (f-5-HT) while it increased plasma
      dopamine (DA) and platelet serotonin (p-5-HT) concentrations within the 4-h study
      period. No adrenaline (Ad) changes were registered. The NA/Ad ratio and the f-5
      HT/p-5-HT ratio showed significant reduction throughout the test. Finally,
      although diastolic blood pressure (DBP) showed significant decrease, neither
      systolic blood pressure (SBP) nor heart rate (HR) showed significant change.
      These findings are consistent with the postulation that tianeptine reduces both
      neural sympathetic activity and parasympathetic activity without affecting
      adrenal sympathetic activity, enabling us to discuss the possible mechanisms
      involved in the antidepressant effects of tianeptine. The well-known fact that
      major depressed patients always show raised NA plus lower than normal p-5-HT
      levels, both disorders which are normalized by tianeptine, gives neurochemical
      support to the clinical improvement triggered by the drug in these patients.
      Summarizing, the results presented in this study demonstrate that tianeptine
      triggers significant reduction of circulating noradrenaline and plasma serotonin
      while increasing circulating dopamine and platelet serotonin. Other possible
      neuropharmacological effects are also discussed.

PMID- 16303224
TI  - Effects of clozapine plus lamotrigine on phencyclidine-induced hyperactivity.
AB  - There is growing evidence from both uncontrolled and controlled clinical studies
      that lamotrigine (LTG) significantly augments clozapine (CLZ) in the treatment of
      refractory schizophrenia (RS) [Dursun, S.M., McIntosh, D., Milliken, H., 1999.
      Clozapine plus lamotrigine in treatment-resistant schizophrenia. Arch. Gen.
      Psychiatry 56, 950; Dursun, S.M., Deakin, J.F.W., 2001. Augmenting antipsychotic
      treatment with lamotrigine or topiramate in patients with treatment-resistant
      schizophrenia: a naturalistic case-series outcome study. J. Psychopharmacol. 15,
      297-301; Tiihonen, J., Hallikainen, T., Ryynanen, O.P., Repo-Tiihonen, E.,
      Kotilinen, I., Eronen, M., Toivonen, P., Wahlbeck, K., Putkonen, A., 2003.
      Lamotrigine in treatment-resistant schizophrenia; a randomized placebo-controlled
      cross over trial. Biol. Psychiatry 54, 1241-1248; Kremer, I., Vass, A., Gorelik,
      I., Bar, G., Blanaru, M., Javitt, D.C., Heresco-Levy, U., 2004. Placebo
      controlled trial of lamotrigine added to conventional and atypical antipsychotics
      in schizophrenia. Biol. Psychiatry. 56, 441-446]. However, the precise mechanism
      of action of this synergistic augmentation between clozapine and lamotrigine
      remains unclear. Therefore, the goal of this research is to explore the mechanism
      of action of this synergistic interaction between CLZ and LTG, utilizing a
      pharmacological animal model of schizophrenia by using phencyclidine (PCP). The
      effects of CLZ plus LTG were assessed by measuring PCP-induced hyper-locomotion
      and stereotyped behaviours in rats. Adult male rats (250-300 g) were pre-treated
      via intra-peritoneal (i.p.) injection with vehicle or drug 30 min before a PCP (5
      mg/kg) or saline challenge. The behaviours were recorded and analysed for a 90
      min period using the Etho Vision-computer based system. PCP produced hyper
      locomotion, which was maximal at 30 min. LTG (10 mg/kg) significantly increased
      hyperlocomotion induced with PCP. However, a combination treatment of CLZ (5
      mg/kg) plus LTG (10 mg/kg) significantly blocked the potentiation of PCP-induced
      hyper-locomotion observed with LTG (10 mg/kg) alone. Furthermore, the PCP-induced
      locomotion in the combination CLZ plus LTG-treated rats was significantly
      decreased when compared to vehicle. Therefore, LTG at doses that do not induce
      ataxia enhanced PCP-induced hyper-locomotion in rats, whereas the combination of
      LTG and CLZ significantly decreased PCP-induced hyper-locomotion consistent with
      clinical data.

PMID- 16303225
TI  - Are nonpharmacological induced rewards related to anhedonia? A study among
      skydivers.
AB  - It is well-known that persons with a drug addiction experience feelings of
      anhedonia during "normal" daily activities. It has been proposed that these
      symptoms of anhedonia are the result of direct pharmacological influences of
      drugs on the dopamine system. To test the assumption that nonpharmacological
      processes are also involved in anhedonia, we studied anhedonic symptoms in
      skydivers who regularly expose themselves to thrillful extreme sport activity and
      then experience intense hedonic feelings. A group of skydivers completed
      anhedonia scales and their scores were compared to a control group (a group of
      rowers). The main finding of the present study was that subjects who engage in
      the high-risk activity of skydiving, experienced more anhedonic symptoms than
      subjects who do not engage in such an extreme sport, but rather prefer a low-risk
      activity like rowing. This finding supports the notion that skydiving has
      similarities with addictive behaviors and that frequent exposure to "natural
      high" experiences is related to anhedonia. This suggests that the negative
      emotional state as observed in drug users may not be exclusively the results of
      exogenous psychopharmacological effects, but might also result from psychological
      mechanisms that are partly responsible for these anhedonic feelings.

PMID- 16303226
TI  - Background noise decreases both prepulse elicitation and inhibition of acoustic
      startle blink responding.
AB  - Prepulse inhibition of startle (PPI) has proved to be useful in distinguishing
      between schizophrenia patients and normal controls, although not all studies in
      this area find such group differences. One reason for this inconsistency may be
      the fact that some research labs present the startle eliciting and inhibiting
      stimuli over a steady background noise (70 dB), whereas others present stimuli in
      ambient noise conditions (30-56 dB). The present study tested the impact of
      background noise (30, 50, and 70 dB) on PPI in normal college adults, with
      prepulses at intensities of 75, 80, and 85 dB, and with prepulse rise times of 1
      or 10 ms. Background noise decreased the amount of PPI caused by the prepulses,
      and also decreased the ability of the prepulses to themselves elicit blink
      responses. We conclude that background noise interferes with the processing of
      the prepulse, attenuating its effect as both an elicitor and inhibitor of the
      startle reflex. By elevating the difficulty of prepulse processing, this
      attenuation may be a necessary condition for observing differences in PPI between
      patient and control groups.

PMID- 16303227
TI  - Lack of association between the CYP11B2 gene polymorphism and preeclampsia,
      eclampsia, and the HELLP syndrome in Turkish women.
AB  - OBJECTIVES: It is possible that altered control of aldosterone synthase gene
      (CYP11B2) expression or translation may be responsible for hypertension.
      Hypertension is one of the major components of preeclampsia. We present here a
      study investigating the association between the CYP11B2 gene polymorphism in the
      promoter region at the position of -344 and preeclampsia. STUDY DESIGN: We
      analyzed a group of Turkish women for preeclampsia (n=143), eclampsia (n=36), and
      the HELLP syndrome (n=55) and compared them with controls (n=147). Genotypes for
      CYP11B2 were determined by polymerase chain reaction followed by digestion with
      BsuRI restriction enzyme. RESULTS: The -344T/T, -344C/T, and -344C/C genotypes
      were found at comparable frequencies among the study groups, between the study
      and control groups, and between the study groups combined and the control group
      (p>0.05). We combined the genotypes of TC and CC (polymorphic) and compared them
      with the TT (wild-type) genotype. There was no significant difference in the
      frequency of the TC plus CC genotypes among the study groups, between the study
      and control groups, and between the study groups combined and the control group
      (p>0.05). There was no association of the CYP11B2 polymorphism among the
      preeclampsia, eclampsia, and HELLP groups and controls. CONCLUSIONS: The CYP11B2
      gene polymorphism is not directly associated with preeclampsia, eclampsia, and
      the HELLP syndrome in women with these conditions. Therefore, this polymorphism
      may not be a risk factor for these disorders, at least not in the Turkish
      population.

PMID- 16303228
TI  - Cost effectiveness of a screen-and-treat program for asymptomatic vaginal
      infections in pregnancy: towards a significant reduction in the costs of
      prematurity.
AB  - OBJECTIVE: The purpose of this investigation was to determine the cost-saving
      potential of a simple screen-and-treat program for vaginal infection, which has
      previously been shown to lead to a reduction of 50% in the rate of preterm
      births. STUDY DESIGN: To determine the potential cost savings, we compared the
      direct costs of preterm delivery of infants with a birth weight below 1900g with
      the costs of the screen-and-treat program. We used a cut-off birth weight of
      1900g because, in our population, all infants with a birth weight below 1900g
      were transferred to the neonatal intensive care unit. The direct costs associated
      with preterm delivery were defined to include the costs of the initial
      hospitalization of both mother and infant and the costs of outpatient follow-up
      throughout the first 6 years of life of the former preterm infant. The costs of
      the screen-and-treat program were defined to include the costs of the screening
      examination and the resulting costs of antimicrobial treatment and follow-up. All
      calculations were based on health-economic data obtained in the metropolitan area
      of Vienna, Austria. RESULTS: The number of preterm infants with a birth weight
      below 1900g was 12 (0.5%) in the intervention group (N=2058) and 29 (1.3%) in the
      control group (N=2097). The direct costs per preterm birth were found to amount
      to EUR (euro) 60262. Overall, the expected total savings in direct costs achieved
      by the screen-and-treat program and the ensuing 50% reduction in the number
      preterm births with a birth weight below 1900g amounted to more than euro 11
      million. The costs of screening and treatment were found to amount to merely 7%
      of the direct costs saved as a result of the screen-and-treat program.
      CONCLUSION: A simple preterm prevention program, consisting of screening and
      antimicrobial treatment and follow-up of women with asymptomatic vaginal
      infection, leads not only to a significant reduction in the rate of preterm
      births but also to substantial savings in the direct costs associated with
      prematurity.

PMID- 16303229
TI  - Intestinal endometriosis without evident pelvic foci treated with gonadotropin
      releasing hormone agonist.

PMID- 16303230
TI  - Receiver operator characteristics and diagnostic value of progesterone and CA-125
      in the prediction of ectopic and abortive intrauterine gestations.
AB  - OBJECTIVE: The study was designed to investigate the predictive value of
      progesterone and CA-125 in the diagnosis of ectopic pregnancy (EP) and inevitable
      miscarriage. METHODS: Forty women with EP, 20 with intrauterine (IU) abortive
      gestation and 20 regular pregnant women (controls) were studied. IU abortive and
      EP were confirmed and treated by surgery. Serum progesterone and CA-125 levels
      were measured at the time of presentation and 24h after surgery. RESULTS: Women
      with EP had significantly lower progesterone concentrations, compared to both
      women with IU abortive pregnancy and controls. Women with IU abortion had
      significantly higher CA-125 levels, compared to the other two groups. When using
      a progesterone concentration of less than 10.75 ng/ml as a cut-point for the
      diagnosis of EP, sensitivity, specificity, positive and negative predictive
      values were 85%. When using CA-125 concentration of more than 41.9 U/ml as a
      threshold for the diagnosis of IU abortive pregnancy, sensitivity was 80%,
      specificity 87%, the positive predictive value was 66% and the negative
      predictive value 93%. CONCLUSION: The measurement of progesterone and CA-125
      levels is useful in discriminating ectopic and intrauterine abortive from normal
      gestations.

PMID- 16303231
TI  - Mistakes prevent mistakes: experience from intraoperative consultation with
      frozen section.

PMID- 16303232
TI  - Correlation between NQR parameters and residue size of aliphatic amino acids and
      their dimers.
AB  - Nuclear quadrupole coupling constants (NQCC), chi, and asymmetry parameters, eta,
      of 2D, 14N and 17O nuclei have been calculated for aliphatic amino acids and
      their dimers using MP2/6-311++G** method to shed some light on the differences
      between the structural parameters in the aliphatic amino acids and their dimers.
      For this purpose, electric field gradient (EFG) at the sites of quadrupolar
      nuclei have been calculated and evaluated for each compound. A correlation is
      observed between the calculated NQCC parameters and the conformational structures
      of the compounds, showing that extraction of structural data from the NQR spectra
      might be promising. Our results showed that 17O NQCC of terminal carboxylic acid
      and 14N NQCC of the terminal amino groups are, respectively, the least and the
      most sensitive parameters to the variation of the size of the residue. It is
      found also that conformation of R (i.e. values of the dihedral angles) plays a
      very effective role in the determination of the values of the calculated NQCC
      parameters. Sensitivity of the NQR parameters to the changes in the
      conformational structure is significantly greater (nearly 20-fold) than that to
      the changes in the other structural parameters such as bond lengths.

PMID- 16303233
TI  - Van't Hoff analysis of K degrees (T): how good...or bad?
AB  - Binding constant data K degrees (T) are commonly subjected to van't Hoff analysis
      to extract estimates of DeltaH degrees, DeltaS degrees, and DeltaCP degrees for
      the process in question. When such analyses employ unweighted least-squares
      fitting of lnK degrees to an appropriate function of the temperature T, they are
      tacitly assuming constant relative error in K degrees. When this assumption is
      correct, the statistical errors in DeltaG degrees, DeltaH degrees, DeltaS
      degrees, DeltaCP degrees, and the T-derivative of DeltaCP degrees (if determined)
      are all independent of the actual values of K degrees and can be computed from
      knowledge of just the T values at which K degrees is known and the percent error
      in K degrees. All of these statistical errors except that for the highest-order
      constant are functions of T, so they must normally be calculated using a form of
      the error propagation equation that is not widely known. However, this
      computation can be bypassed by defining DeltaH degrees as a polynomial in (T-T0),
      the coefficients of which thus become DeltaH degrees, DeltaCP degrees, and 1/2
      dDeltaCP degrees/dT at T=T0. The errors in the key quantities can then be
      computed by just repeating the fit for different T0. Procedures for doing this
      are described for a representative data analysis program. Results of such
      calculations show that expanding the T range from 10-40 to 5-45 degrees C gives
      significant improvement in the precision of all quantities. DeltaG degrees is
      typically determined with standard error a factor of approximately 30 smaller
      than that for DeltaH degrees. Accordingly, the error in TDeltaS degrees is nearly
      identical to that in DeltaH degrees. For 4% error in K degrees, the T-derivative
      in DeltaCP degrees cannot be determined unless it is approximately 10 cal mol-1 K
      2 or greater; and DeltaCP degrees must be approximately 50 cal mol-1 K-1. Since
      all errors scale with the data error and inversely with the square root of the
      number of data points, the present results for 4% error cover any other relative
      error and number of points, for the same approximate T structure of the data.

PMID- 16303234
TI  - Inhibition of DNA hybridization by small metal nanoparticles.
AB  - The inhibition of DNA hybridization by small metal nanoparticles has been
      examined in detail. DNA melting point analysis showed that the oligonucleotides
      adsorb strongly and nonspecifically on small metal nanoparticles, inhibiting the
      hybridization of complementary DNA sequences in common buffered solutions. The
      nonspecific interaction is even strong enough to disrupt pre-existing hydrogen
      bonds in short double-stranded DNA. The nonspecific interaction could be weakened
      by increasing the particle size. As an example, a core-shell assisted method was
      used to successfully assemble Pt nanoparticles by DNA hybridization that could
      not be done otherwise.

PMID- 16303235
TI  - Regeneration of Nothofagus pumilio [Poepp. et Endl.] Krasser forests after five
      years of seed tree cutting.
AB  - Nothofagus pumilio [Poepp. et Endl.] Krasser is a deciduous tree species that
      grows in Chile and adjacent Argentina between 36 and 56 degrees S, often forming
      the Andean tree line. Silvicultural systems proposed for this species integrate
      both regeneration and intermediate level operations in an orderly process for
      managing forest stands. The seed-tree method of regeneration has been used to
      manage even-aged stands of this species. This paper investigates the effect of
      seed tree cuttings on the regeneration of Nothofagus pumilio [Poepp. et Endl.]
      Krasser forest located in the Magallanes region (Chile). The studied forest was
      managed on an even-aged basis using a seed tree silvicultural system for
      regeneration with an intensity of cutting of 65-70% of the basal area and a
      minimum of 15 dominant lenga trees per hectare retained. A regeneration inventory
      sampling was used to quantify regeneration attributes in the study area.
      Regeneration was found to be significantly affected by the seed tree cuttings. In
      fact, the number of established individuals rose from 0.39 to 26.7 plants m(-2)
      pre-harvest to 9.2-21.5 plants m(-2) post-harvest, depending on the particular
      development stage. Total regeneration ranged from 9.5 to 48.2 plants m(-2). The
      number of plants established over the period 1992-1997 was related to the
      residual basal area, coverage and number of trees. However, mean tree height was
      not significantly related to any regeneration variable. Significant variables
      were used to establish a regeneration prediction model using single and multiple
      linear equations (R2<0.418). Consequently, the seed tree method of regeneration
      can be considered feasible for commercially valuable lenga forests, although this
      method, in its strictest application, will create many large, irregularly shaped,
      even-aged groups.

PMID- 16303236
TI  - Overland flow model for asphalt oil spills.
AB  - Along the asphalt production line, the hot asphalt oil needs to undergo a cooling
      process that involves temporary storage in a tank. Safety is always a concern as
      to what if the tank is ruptured. Scenario studies of asphalt oil spills are
      required when designing the layout and open space for such a cooling process in
      the refinery yard. Applying the laminar flow theory to an asphalt oil spill, this
      paper presents an overland flow model to calculate the possible range of spread.
      The major parameters used in this model include fluid viscosity, ground slope,
      hydraulic conveyance, and asphalt oil volume. As a simplified model for a quasi
      steady state flow condition, a hot asphalt oil spill for a typical case in a
      refinery yard can run approximately 400 to 600 feet before the asphalt mass cools
      down and becomes solid-like.

PMID- 16303237
TI  - An efficient technology to treat heavy metal--lead--contaminated soil by
      microwave radiation.
AB  - Microwave (MW) technology can be used to vitrify contaminated soil wastes and
      immobilize heavy metal ions in soils. More than 93% of the Pb(II)-contaminated
      soil was vitrified to a glass/ceramic formation after 30 min of MW radiation. In
      a 6-year study, the Pb(II) concentration of the vitrified soil in the leaching
      test was less than 1.0 mg/l, which is substantially below the USEPA regulatory
      limit of 5.0 mg/l.

PMID- 16303238
TI  - Estimating the effects of urban residential development on water quality using
      microdata.
AB  - In this study, we examine the impact on water quality of urbanization using
      disaggregate data from Wake County, North Carolina. We use a unique panel data
      set tracing the conversion of individual residentially zoned land parcels to
      relate the density of residential development and the change in residential land
      use to three measures of water quality. Using a spatial econometrics model, we
      relate spatially and temporally referenced monitoring station readings to our
      measures of residential land use while controlling for other factors affecting
      water quality. We find that both the density of residential land use and the rate
      of land conversion have a negative impact on water quality. The impacts of these
      non-point sources are found to be larger in magnitude than those from urban point
      sources.

PMID- 16303239
TI  - Metabolomic networks in plants: Transitions from pattern recognition to
      biological interpretation.
AB  - Nowadays techniques for non-targeted metabolite profiling allow for the
      generation of huge amounts of relevant data essential for the construction of
      dynamic metabolomic networks. Thus, metabolomics, besides transcriptomics or
      proteomics, provides a major tool for the characterization of postgenomic
      processes. In this work, we introduce comparative correlation analysis as a
      complementary approach to characterize the physiological states of various organs
      of diverse plant species with focus on specific participation of metabolites in
      different reaction networks. The correlations observed are induced by diminutive
      fluctuations in environmental conditions, which propagate through the system and
      induce specific patterns depending on the genomic background. In order to examine
      this hypothesis, numeric examples of such fluctuations are computed and compared
      with experimentally obtained metabolite data.

PMID- 16303240
TI  - Generalized concept of minimal cut sets in biochemical networks.
AB  - Recently, the concept of minimal cut sets has been introduced for studying
      structural fragility and identifying knock-out strategies in biochemical reaction
      networks. A minimal cut set (MCS) has been defined as a minimal set of reactions
      whose removal blocks the operation of a chosen objective reaction. In this report
      the theoretical framework of MCSs is refined and extended increasing the
      practical applicability significantly. An MCS is now defined as a minimal
      (irreducible) set of structural interventions (removal of network elements)
      repressing a certain functionality specified by a deletion task. A deletion task
      describes unambiguously the flux patterns (or the functionality) to be repressed.
      It is shown that the MCSs can be computed from the set of target modes, which
      comprises all elementary modes that exhibit the functionality to be attacked.
      Since a deletion task can be specified by several Boolean rules, MCSs can now be
      determined for a large variety of complex deletion problems and may be utilized
      for inhibiting very special flux patterns. It is additionally shown that the
      other way around is also possible: the elementary modes belonging to a certain
      functionality can be computed from the respective set of MCSs. Therefore,
      elementary modes and MCSs can be seen as dual representations of network
      functions and both can be converted into each other. Moreover, there exist a
      strong relationship to minimal hitting sets known from set theory: the MCSs are
      the minimal hitting sets of the collection of target modes and vice versa.
      Another generalization introduced herein is that MCSs need not to be restricted
      to the removal of reactions they may also contain network nodes. In the light of
      the extended framework of MCSs, applications for assessing, manipulating, and
      designing metabolic networks in silico are discussed.

PMID- 16303241
TI  - Prevention of osteoporosis in glucocorticoid-treated neurology patients.
AB  - OBJECTIVES: Iatrogenic, including corticosteroid-induced osteoporosis is
      preventable with administration of osteoprotective biphosphonates. The best
      medical practice is published in the National Guidelines: UK Osteoporosis
      Consensus Group (1998, update 2002). We conducted an audit in prednisolone
      treated general neurology patients, to assess compliance to national guidelines,
      raise awareness of osteoporosis prevention, and improve clinical practice in a
      tertiary neurology referral centre. METHODS AND RESULTS: Preintervention: Of the
      48 cases (21 male) identified twenty-nine (61%) received osteoporosis
      prophylaxis. Nineteen (40%) were given biphosphonates, while 10 (21%) hormone
      replacement therapy or calcium and Vitamin D. INTERVENTION: Results were
      presented to the consultant body. Postintervention: Data were collected
      prospectively on 48 patients (30 male) in year 2001. Thirty-eight (79%) received
      prophylaxis: 35 (73%) were started on biphosphonates, while 3 (6%) on calcium and
      Vitamin D. This process was repeated 2 years later to assess sustainability. Of
      the 48 patients, 44 (92%) received prophylaxis: 41 (86%) were taking
      biphosphonates, while 3 (6%) calcium and Vitamin D. CONCLUSION: We present an
      original and complete audit on osteoporosis prophylaxis in a typical population
      of neurology patients. Though initial results were similar to previous reports,
      our audit led to significant improvement in clinical practice. National
      guidelines could not be followed meticulously, as our centre has no regular
      access to bone densitometry. Our patient population had other risk factors for
      osteoporosis apart from steroid use. Therefore, we recommend that neurologists in
      this setting use osteoporosis prophylaxis for all their patients on long-term
      corticosteroids.

PMID- 16303242
TI  - Translesion DNA replication proteins as molecular targets for cancer prevention.
AB  - Mutations in DNA are generally considered to have an etiologic role in the
      development of cancer. If so, it follows that reducing the frequency of such
      mutations will reduce the incidence of cancer induced by mutagens. Recent
      advances in elucidating the molecular mechanisms of carcinogen-induced
      mutagenesis indicate that replication of DNA templates that contain replication
      blocking adducts is accomplished with error-prone DNA polymerases. These
      polymerases have relaxed base-pairing requirements, and can insert bases across
      from adducted templates, but with potentially mutagenic consequences. In
      principle, these proteins present new and attractive molecular targets to reduce
      mutagenesis. If this can be done in vivo without increasing cytotoxic responses
      to carcinogens, then novel chemopreventive strategies can be designed to reduce
      the risk of cancer in exposed populations prior to the appearance of disease
      symptoms.

PMID- 16303243
TI  - Functional SNPs of the breast cancer resistance protein-therapeutic effects and
      inhibitor development.
AB  - Breast cancer resistance protein (BCRP) is a half-molecule ATP-binding cassette
      transporter that pumps out various anticancer agents such as 7-ethyl-10
      hydroxycamptothecin, topotecan and mitoxantrone. We have previously identified
      three polymorphisms within the BCRP gene, G34A (substituting Met for Val-12),
      C376T (substituting a stop codon for Gln-126) and C421A (substituting Lys for Gln
      141). C421A BCRP-transfected murine fibroblast PA317 cells showed markedly
      decreased protein expression and low-level drug resistance when compared with
      wild-type BCRP-transfected cells. In contrast, G34A BCRP-transfected PA317 cells
      showed a similar protein expression and drug resistance profile to wild-type. The
      C376T polymorphism would be expected to have a considerable impact as active BCRP
      protein will not be expressed from a T376 allele. Hence, people with C376T and/or
      C421A polymorphisms may express low levels of BCRP, resulting in hypersensitivity
      of normal cells to BCRP-substrate anticancer agents. Estrogens, estrone and
      17beta-estradiol, were previously found to restore drug sensitivity levels in
      BCRP-transduced cells by increasing the cellular accumulation of anticancer
      agents. BCRP transports sulfated estrogens but not free estrogens and in a series
      of screening experiments for synthesized and natural estrogenic compounds,
      several tamoxifen derivatives and phytoestrogens/flavonoids were identified that
      effectively circumvent BCRP-mediated drug resistance. The kinase inhibitors
      gefitinib and imatinib mesylate also interact with BCRP. Gefitinib, an inhibitor
      of epidermal growth factor receptor-tyrosine kinase, inhibits its transporter
      function and reverses BCRP-mediated drug resistance both in vitro and in vivo.
      BCRP-transfected human epidermoid carcinoma A431 cells and BCRP-transfected human
      non-small cell lung cancer PC-9 cells show gefitinib resistance. Imatinib, an
      inhibitor of BCR-ABL tyrosine kinase, also inhibits BCRP-mediated drug transport.
      Hence, both functional SNPs and inhibitors of BCRP reduce its transporter
      function and thus modulate substrate pharmacokinetics and pharmacodynamics.

PMID- 16303244
TI  - Dual function of (--)-epigallocatechin gallate (EGCG) in healthy human
      lymphocytes.
AB  - (-)-Epigallocatechin gallate (EGCG), a catechin polyphenol component, is the main
      ingredient of green tea extract. Recently, increasing attention has been given to
      its anti-oxidant effects. However, several studies reported the oxidative effects
      of EGCG, suggesting that EGCG had a dual function of anti-oxidant and pro-oxidant
      potentials. In this study, we examined the influences of EGCG on healthy human
      whole blood lymphocytes and purified blood lymphocytes using a single-cell gel
      electrophoresis (SCG) assay. The results showed that EGCG suppressed the DNA
      strand breakage in whole blood lymphocytes at concentrations from 10(-8) to 10(
      5)M, while it induced DNA strand breakage at concentration of 10(-3)M.
      Furthermore, EGCG at concentrations of 10(-6)-10(-4)M suppressed the DNA strand
      breakage induced by bleomycin (BLM) and H(2)O(2) in whole blood lymphocytes. In
      the same range of 10(-6)-10(-4)M, EGCG increased DNA strand breakage in purified
      blood lymphocytes, but suppressed the DNA breakage induced by BLM at lower
      concentrations from 10(-8) to10(-7)M. From these findings, we propose that EGCG
      might have a dual function of anti-oxidant and pro-oxidant in healthy human
      lymphocytes, which would involved in its inhibitory effects against DNA strand
      breakage induced by BLM and H(2)O(2).

PMID- 16303245
TI  - Methylation and expression analysis of 15 genes and three normally-methylated
      genes in 13 Ovarian cancer cell lines.
AB  - Aberrant methylation of CpG islands (CGIs) in promoter regions of tumor
      suppressor genes causes their silencing, and aberrant demethylation of normally
      methylated CGIs in promoter regions causes aberrant expression of cancer-testis
      antigens. Here, we comprehensively analyzed aberrant methylation of 15 genes and
      demethylation of three normally methylated genes in 13 ovarian cancer cell lines.
      RASSF1A was most frequently methylated (complete methylation in 7 and partial
      methylation in 4 cell lines), followed by ESR1 (5 and 2, respectively), FLNC (4
      and 4), HAND1 (4 and 2), LOX (3 and 2), HRASLS (3 and 2), MGMT (3 and 0), CDKN2A
      (3 and 0), THBD (2 and 1), hMLH1 (2 and 0), CDH1 (1 and 1) and GSTP1 (1 and 0).
      hTERC and TIMP3 were only partially methylated in 7 and 2 cell lines,
      respectively. BRCA1 was not methylated at all. Aberrant demethylation of MAGE-A3,
      -B2 and -A1 was detected in 8, 4 and 3 cell lines, respectively. Gene expression
      was consistently absent in cell lines without unmethylated DNA molecules.
      Aberrant methylation was frequently observed in MCAS, RMUG-L (mucinous cell
      carcinomas), RTSG (poorly-differentiated carcinoma) and TYK-nu (undifferentiated
      carcinoma) while infrequent in HTOA, JHOS-2, and OV-90 (serous cell carcinomas).
      Aberrant demethylation was frequently observed in OV-90, OVK-18, and ES-2 cell
      lines. It was shown that aberrant methylation and demethylation were frequently
      observed in ovarian cancer cell lines, and these data will provide a basis for
      further epigenetic analysis in ovarian cancers.

PMID- 16303246
TI  - The phototoxicity of photofrin was enhanced by PEGylated liposome in vitro.
AB  - In recent years, photodynamic therapy (PDT) with a photosensitizer and laser has
      been given attention, especially for the treatment of superficial cancers, such
      as lung, gastric, bladder and cervical cancer. In this study, in order to enhance
      the efficacy of PDT, photofrin liposome (PF-Lip) was prepared with
      dimyristoylphosphatidylcholine, dimyristoylphosphatidylglycerol and cholesterol.
      Polyethyleneglycol modified photofrin liposome (PF-PEG-Lip) was prepared by
      modification of PF-Lip with monomethoxypolyethyleneglycol-2.3
      dimyristoylglycerol. PF-Lip and PF-PEG-Lip entrapped with photofrin with 81.0+/
      5.9 and 81.2+/-9.2%, respectively. The particle size of each liposome was 114.3+/
      5.7nm (PF-Lip) and 118+/-3.5nm (PF-PEG-Lip), respectively. It was suggested that
      PEGylated liposomes has no effect on the trapping ratio of PF and particle size.
      Phototoxicity was enhanced by liposomalization, especially PEG-modification.
      However, PF-PEG-Lip inhibited the uptake of photofrin into tumor cells. The
      amount of singlet oxygen from photofrin solution (PF-sol) and each liposome was
      PF-PEG-Lip=PF-Lip>PF-sol. The photofrin release revel of PF-PEG-Lip was lower
      than that of PF-Lip. In conclusion, the phototoxicity of PF-PEG-Lip was
      significantly higher than that of PF-sol or PF-Lip. It is expected that formation
      of a fixed aqueous layer on the liposome membrane by PEGylation physically
      changed it into the stable state of PF-PEG-Lip.

PMID- 16303247
TI  - Expression of Stat5A in tobacco chewing-mediated oral squamous cell carcinoma.
AB  - Oral squamous cell carcinoma (oscc) is the fifth most common cancer worldwide and
      the number of cases is increasing regularly in the developing world. The
      effective detection of oscc at its early stages becomes necessary for proper
      treatment due to limited understanding of the critical pathways during
      oncogenesis. Signal transducer and activators of transcription (Stats) are an
      important group of transcription factors, which contribute to tumorigenesis due
      to their intimate connection to growth factor signalling, apoptosis, and
      angiogenesis. They also play a critical role in immune responses and hence
      defective Stat signalling could favour tumour development by compromising immune
      surveillance. The role of Stat5A in mammary gland carcinoma and leukaemia has
      already been reported. We for the first time report here the constitutive
      activation of Stat5A as one of the early events in tobacco mediated-oscc in the
      eastern Indian population, which can be used as a potent prognostic molecular
      marker.

PMID- 16303248
TI  - Delivery of hypericin for photodynamic applications.
AB  - Early cancer detection is critical in improving disease management outcomes.
      Cancer diagnosis presents unique difficulties mainly due to its pathological
      presentation and poor accessibility that could limit the usefulness of
      conventional white light endoscopy in early cancer detection. Fluorescence
      endoscopy has been proven to improve the sensitivity and specificity of early
      cancer detection. Hypericin (HY) has been found to be superior to 5
      aminolevulinic acid (5-ALA) and its ester derivative hexaminolevulinate (HA) as a
      fluorescence diagnostic agent, hence its development for delivery in vitro and in
      vivo, is the subject of this review.

PMID- 16303249
TI  - Treatment of poultry slaughterhouse wastewaters by electrocoagulation.
AB  - Treatment of poultry slaughterhouse wastewater (PSW) by electrocoagulation (EC)
      has been investigated batchwise in this paper. Effects of the process variables
      such as medium pH, electrode material, current density, and operating time are
      investigated on chemical oxygen demand (COD) and oil-grease removal efficiencies,
      electrical energy consumption, and sacrificial electrode consumption. The highest
      COD removal efficiency is reached with aluminum as 93%, and maximum oil-grease
      removal is obtained with iron electrodes as 98%. Combined use of both electrode
      materials in the EC unit may yield high process performances with respect to both
      COD and oil-grease removals. Further work needs to be carried out at pilot scale
      to assess the technical end economic feasibility of the process.

PMID- 16303250
TI  - Removal kinetics of acetone and MIBK from a complex industrial wastewater by an
      acclimatized activated sludge.
AB  - Removal rates of acetone and methyl isobutyl ketone (MIBK) were determined
      singularly and in combination in batch experiments employing an acclimatized
      activated sludge from a pilot system treating an organic chemical manufacturer
      industrial wastewater, as well as during the course of operation of the pilot
      system. Both acetone and MIBK removals were described by first-order removal
      kinetics. Acetone, as a single substrate, was biodegraded at a rate of 1.7 day(
      1). MIBK was biodegraded, during the single-substrate experiments, at an observed
      rate of 2.23 day(-1). Relative to the control (no spike) experiments, acetone
      removal was augmented by a factor of 3 during the acetone spike, with an observed
      biomass-specific removal rate of 0.0023 L/mg VSSday. MIBK removal during an MIBK
      spike was also enhanced by a factor of 2, and the greatest biomass-specific
      removal rate of MIBK was observed during the acetone spike of 0.0019 L/mg VSSday.
      The observed rates were approximately 3 orders of magnitude greater than the
      observed rates in the pilot scale system. MIBK exerted a synergistic effect on
      the acetone-removal rate while acetone exerted an inhibitory impact on the MIBK
      removal rate.

PMID- 16303251
TI  - A new route to non invasive diagnosis in neurodegenerative diseases?
AB  - We propose a simple dynamical system to interpret the gait time series from
      patients affected by three neurodegenerative diseases: Parkinson, Huntington and
      Amyotrophic Lateral Sclerosis. The model is shown to reproduce the main aspects
      of the experimental time series. Within this scenario, quantitative differences
      in specific indicators are detected thus opening up the perspective for
      innovative, non invasive, diagnosis procedures from direct measurements of gait
      dynamics.

PMID- 16303252
TI  - Field efficacy of minidosed eprinomectin against Hypoderma spp. in dairy cattle.
AB  - A chemoprophylactic field trial was conducted to assess the efficacy of pour-on
      eprinomectin applied at the approximate dose of 50 mcg/kg to dairy cattle with
      naturally occurring hypodermosis. Two-hundred-eleven cattle, selected from two
      herds with a high prevalence of Hypoderma spp. infestation, were divided in three
      groups: Group A (N = 71) was treated with pour-on eprinomectin at the recommended
      dosage of 500 mcg/kg, Group B (N = 64) at the lower dose of 50 mcg/kg, a third
      group (Group C, N = 76) served as untreated control group. Treatments were
      performed in November-December 2002 and the animals were examined for the
      presence of warbles in the following April and June. No larvae emerged in the
      treated groups, whereas a variable number of warbles (ranging from 1 to 28) were
      found in control animals. Adverse reactions were not observed in any animal, and
      only minor side effects were observed. A larger field trial carried out in the
      following year (1064 treated and 131 untreated control cattle) confirmed the
      chemoprophylactic efficacy of minidosed eprinomectin against Hypoderma spp.
      Administration of eprinomectin minidoses in dairy cattle is interesting because
      of the low costs involved and no need for milk withdrawal.

PMID- 16303253
TI  - Improved methods for isolating DNA from Ostertagia ostertagi eggs in cattle
      feces.
AB  - A multiplex PCR assay for differentiating strongyle eggs from cattle has recently
      been described; however, the egg disruption and DNA extraction procedures, though
      effective, are inadequate for large studies or clinical application. The purpose
      of this research was to evaluate methods for disrupting trichostrongyle eggs,
      then assess commercial kits for extracting egg DNA using Ostertagia ostertagi as
      a model species. Egg disruption procedures tested included probe sonication, bath
      sonication, bead beating, boiling, microwaving, proteinase K/SDS digestion,
      freezing, and various combinations of the above with the incorporation of sodium
      dodecyl sulfate. These procedures were evaluated in conjunction with four
      commercial DNA extraction kits: DNA Stool mini kit and DNeasy Plant kit (Qiagen),
      Fast DNA kit (QBiogene), and the MAP extraction kit (Tetracore). Results showed
      that egg disruption was best accomplished with the bead beater and ceramic beads,
      resulting in 100% disruption within 1min. When DNA extraction was preceded by the
      isolation of eggs from feces, all procedures except the Fast DNA kit produced PCR
      ready DNA from at least two eggs. The DNeasy Plant kit allowed consistent
      detection of DNA released from one egg. Due to the morphological similarities
      among trichostrongyle eggs in ruminants, strongyle eggs in equids, and hookworm
      eggs, the methods described herein may have broad application to other nematodes.

PMID- 16303254
TI  - The transmissibility of Trypanosoma congolense seems to be associated with its
      level of resistance to isometamidium chloride.
AB  - In large parts of Africa the control of livestock trypanosomiasis relies on the
      use of trypanocidal drugs. Resistance against the available compounds is
      developing rapidly in the trypanosome population. The effect of the development
      of drug resistance on the fitness of the trypanosome is not well known. To
      determine the effect of the development of resistance to isometamidium chloride
      on the trypanosome's transmissibility, transmission experiments were conducted.
      Use was made of three isogenic clones of Trypanosoma congolense with different
      susceptibility to the drug. The infection rate in Glossina morsitans morsitans
      differed significantly between clones and was significantly higher in tsetse
      flies infected with the T. congolense clone with the highest level of drug
      resistance.

PMID- 16303255
TI  - Transgenic mice over-expressing human beta-amyloid have functional nicotinic
      alpha 7 receptors.
AB  - A potentially major factor in the development of Alzheimer's disease is the
      enhanced production of soluble beta-amyloid peptide fragments amyloid beta
      peptide(1-40) and amyloid beta peptide(1-42). These amyloid peptides are
      generated by cleavage of the amyloid-precursor protein and aggregate
      spontaneously to form amyloid plaques, which are a classical pathological
      hallmark in Alzheimer's disease. Although the precise mechanisms are unknown, it
      is widely believed that amyloid peptides initiate the degenerative process,
      resulting in subsequent cognitive decline. One interaction of amyloid beta
      peptide that may contribute to an impairment of cognition is its high affinity
      binding to the alpha 7 nicotinic receptor; a receptor shown to be important for
      cognition in a number of studies. There is some controversy, however, whether
      amyloid beta peptide inhibits or activates this receptor. We have cloned and
      stably expressed the human alpha 7 receptor and investigated its interaction with
      amyloid beta peptide using patch clamp electrophysiology. Human alpha 7 was
      activated in a concentration-dependent fashion by nicotine, acetylcholine and
      choline and potently inhibited by methyllycaconitine citrate. The responses were
      inwardly rectifying and exhibited rapid activation, desensitization and
      deactivation. Amyloid beta peptide(1-42) antagonized human alpha7 responses in a
      partially reversible fashion; no agonist effects of amyloid beta peptide(1-42)
      were detected. A similar inhibition of mouse alpha 7 was also observed. In
      addition, we have assessed the function of native alpha 7 receptors in
      hippocampal slices prepared from transgenic mice that over-express human amyloid.
      Despite this clear inhibition of recombinant receptors, hippocampal GABAergic
      interneurones in slices from beta-amyloid over-expressing mice still possess
      alpha 7 receptor-mediated currents.

PMID- 16303256
TI  - Decreased brain tryptophan availability as a partial determinant of post-partum
      blues.
AB  - BACKGROUND: The post-partum blues is a transient mood alteration affecting most
      women a few days after delivery. Its stereotypic pattern of symptoms and time
      course, peaking on post-partum day 3-5, is suggestive of biological determinants
      superimposed on psycho-social factors. This study was designed to evaluate the
      possible role of the serotonin system during this period through assessment of
      brain tryptophan availability. METHODS: Blood samples from 50 women were
      collected just before (D0) and 3 days after (D3) delivery. Based on plasma
      concentration of tryptophan, amino acids competing with tryptophan for transport
      across the blood-brain barrier and on their respective affinities for this
      transporter, a brain tryptophan availability index (BTAI) was calculated and its
      variation correlated with the intensity of post-partum blues evaluated through
      the Kennerley and Gath score at D3. RESULTS: The BTAI showed a -15% decrease
      between D0 and D3 (p < 0.01, paired t-test). This decrease was not supported by a
      drop in plasma tryptophan since its level rather increased (+19%). There was no
      evidence for change in placental indoleamine-2,3-dioxygenase activity since the
      variation in plasma l-kynurenine (+12%) paralleled the change in tryptophan
      level. The decreased BTAI appeared the consequence of a dramatic increase in
      plasma levels of most amino acids, particularly the competitor aminoacids
      leucine, isoleucine, valine and tyrosine, during the early post-partum. This
      decrease in brain tryptophan availability was concomitant to the post-partum
      blues, whose intensity significantly correlated with the amplitude of BTAI
      variation (Pearson's coefficient -0.283, p < 0.05). CONCLUSION: This study
      suggests that generalized, large amplitude metabolic and/or nutritional changes
      occurring in the early post-partum result in a transient decrease in brain
      tryptophan availability, partly accounting for the mood alteration referred to as
      the post-partum blues, a model for the triggering of puerperal mood disorder in
      vulnerable women.

PMID- 16303257
TI  - Shorter time to first cigarette of the day in menthol adolescent cigarette
      smokers.
AB  - Menthol smoking is thought to contribute to the addictiveness of smoking. Given
      the high prevalence of menthol smoking among youth, the aim of the current
      analysis was to examine differences in consumption and tobacco dependence,
      including smoking urgency among menthol and non-menthol adolescent smokers. Data
      for the current analysis were collected from telephone interviews with adolescent
      smokers applying to a cessation treatment study. Of 572 adolescent smokers (mean
      age=15.6+/-1.6 years; 55.1% female; 46.9% African American, 48.2% European
      American), 531 smoked menthol cigarettes and 41 smoked non-menthol as their usual
      brand. Analysis using Fisher's Exact (one-tailed) Test revealed that menthol
      smokers had a significantly shorter time to first (TTF) cigarette of the day
      compared to non-menthol smokers (smoking within the first 5 min of the day, 45%
      vs. 29%, respectively; p<0.04). Independent t tests revealed no significant
      difference in number of cigarettes per day (CPD) (mean=12.2+/-8.5 vs. 11.4+/-8.8;
      p<0.28) or Fagerstrom Test for Nicotine Dependence (FTND) scores (3.4+/-1.4 vs.
      3.2+/-1.3; p<0.23). While preliminary, our findings suggest greater smoking
      urgency among menthol compared to non-menthol adolescent cessation-treatment
      seekers. Further study in a broader sample of adolescent smokers is warranted to
      elucidate the mechanisms underlying the effects of menthol smoking for youths.

PMID- 16303258
TI  - Using the transcriptome to annotate the genome revisited: application of
      massively parallel signature sequencing (MPSS).
AB  - Transcriptome analysis can provide useful data for refining genome sequence
      annotation. Application of massively parallel signature sequencing (MPSS)
      revealed reproducible transcription, in multiple MPSS cycles, from 73% of
      computationally predicted genes in the Theileria parva schizont lifecycle stage.
      Signatures spanning consecutive exons confirmed 142 predicted introns. MPSS
      identified 83 putative genes, >100 codons overlooked by annotation software, and
      139 potentially incorrect gene models (with either truncated ORFs or overlooked
      exons) by interfacing signature locations with stop codon maps. Twenty
      representative models were confirmed as likely to be incorrect using reverse
      transcription PCR amplification from independent schizont cDNA preparations. More
      than 50% of the 60 putative single copy genes in T. parva that were absent from
      the genome of the closely related T. annulata had MPSS signatures. This study
      illustrates the utility of MPSS for improving annotation of small, gene-rich
      microbial eukaryotic genomes.

PMID- 16303259
TI  - The Debaryomyces hansenii NHA1 gene encodes a plasma membrane alkali-metal-cation
      antiporter with broad substrate specificity.
AB  - Debaryomyces hansenii is a yeast species often found in salty environments. Its
      genome sequence is known completely, but the mechanisms behind its halotolerance
      are poorly understood. In the D. hansenii genome, there is a gene strongly
      homologous to the Saccharomyces cerevisiae NHA1 gene (encoding a plasma membrane
      Na+/H+ antiporter). We isolated this DhNHA1 gene from two D. hansenii strains
      (CBS 767 and CBS 1793) differing in their osmotolerance. Both DhNHA1 alleles were
      heterologously expressed in a S. cerevisiae strain lacking its own systems for
      the efflux of alkali metal cations (BW31a, ena1-4delta nha1delta). D. hansenii
      Na+/H+ antiporters were localized in the plasma membrane of BW31a cells, their
      presence increased BW31a tolerance to sodium, potassium, lithium and also
      rubidium. Measurements of Na+ and K+ efflux from S. cerevisiae cells expressing
      DhNHA1 alleles show that the D. hansenii antiporters efficiently transported both
      cations out of cells. The sodium and potassium transport activity of Nha1
      antiporters from both D. hansenii strains was almost identical, indicating that
      plasma membrane antiporter activity is not one of the factors determining the
      different levels of halotolerance in the two strains.

PMID- 16303260
TI  - Growth hormone transcription factor ZN-16 genomic coding regions are composed of
      a single exon and are evolutionarily conserved in mammals.
AB  - The structure of the gene encoding ZN-16, a transcription factor that binds to
      the mammalian growth hormone promoter in tandem with Pit-1, was determined in
      order to elucidate the exon-intron organization of the 16 zinc finger domains of
      the protein. Southern hybridization of mouse genomic DNA showed fragments with
      sizes identical to those predicted from mouse ZN-16 cDNA for two different probes
      covering the 2200 aa coding frame. Mouse genome database sequences also showed no
      introns in the zn-16 coding regions on chromosome 4. Analysis of human zn-16 by
      Southern hybridization and genomic database sequence analysis also indicated a
      single exon for the human protein coding sequences. BLASTP query of available
      genomic databases with critical zinc finger residues from mouse ZN-16 identified
      highly similar canine, bovine, and chimpanzee genomic sequences that encode
      proteins. Phylogenetic analysis of these mammalian proteins resulted in
      relationships as would be expected in species spanning rodents to humans. All six
      independent zn-16 sequences show a single exon coding region with no introns, a
      similarity ruling out the possibility that these genomic sequences are
      pseudogenes. Thus, mammalian zn-16 has a compact single exon structure encoding a
      very large protein (2200-3000 aa), the conservation of which may have functional
      implications such as the importance of posttranscriptional modifications.

PMID- 16303261
TI  - Shedding of feline leukemia virus RNA in saliva is a consistent feature in
      viremic cats.
AB  - The purpose of this investigation was to characterize the shedding pattern of
      feline leukemia virus (FeLV) RNA in saliva, and to correlate it with the proviral
      load in whole blood, viral load in plasma, levels of p27 in saliva and plasma,
      the isolation of infectious FeLV from saliva, and the titers of FeLV-specific
      antibodies of the IgG and IgA isotypes. We evaluated 24 experimentally FeLV
      infected cats for these parameters using real-time RT-PCR and PCR, cell culture
      assay and sandwich ELISA. We observed that shedding of viral RNA in saliva was a
      consistent feature in viremic cats. Latently FeLV-infected cats, displaying a
      very low proviral load, did not shed infectious virus in saliva, but occasionally
      shed viral RNA. Consequently, salivary shedding of FeLV RNA may not necessarily
      indicate a transmission potential for susceptible cats. This study also confirmed
      previous results from our laboratory, showing that a negative result for p27 in
      plasma, or for viral RNA in plasma or saliva does not exclude FeLV infection,
      considering that blood cells from those cats contained provirus. We also showed
      that FeLV RNA and DNA were stable for more than 64 days in saliva samples stored
      at room temperature. We conclude that the detection of FeLV RNA in saliva may be
      a useful indicator of viremia, and that the detection of salivary viral RNA by RT
      PCR could become a reliable tool for the diagnosis of FeLV infection, which is
      facilitated by the low invasive method of collection of the samples.

PMID- 16303262
TI  - Distribution and function of plasmids in Salmonella enterica.
AB  - Plasmids of Salmonella enterica vary in size from 2 to more than 200 kb. The best
      described group of plasmids are the virulence plasmids (50-100 kb in size)
      present in serovars Enteritidis, Typhimurium, Dublin, Cholerae-suis, Gallinarum,
      Pullorum and Abortus-ovis. They all encode spvRABCD genes involved in intra
      macrophage survival of Salmonella. Another group of high molecular weight
      plasmids are plasmids responsible for antibiotic resistance. Since most of these
      plasmids are conjugative, besides storage of genetic information, they contribute
      to the spread of genes in bacterial populations. The low molecular weight
      plasmids are the last group of plasmids found in S. enterica. Some of them have
      been shown to increase resistance to phage infection due to the presence of
      restriction modification systems. Despite limited knowledge on their function,
      their presence or absence is frequently used for strain differentiation in
      epidemiological studies.

PMID- 16303263
TI  - The two major subspecies of Fusobacterium necrophorum have distinct leukotoxin
      operon promoter regions.
AB  - Fusobacterium necrophorum, a gram-negative, non-spore-forming anaerobe, is a
      normal inhabitant of the alimentary tract of animals and humans. Two types of F.
      necrophorum, subspecies necrophorum (biotype A) and funduliforme (biotype B),
      have been recognized, which differ morphologically, biochemically and
      biologically. The organism is an opportunistic pathogen that causes numerous
      necrotic conditions (necrobacillosis) such as bovine hepatic abscesses and
      ruminant foot abscesses. Subspecies necrophorum strains are considered to be more
      virulent for cattle and have been shown to produce greater amounts of leukotoxin
      than subspecies funduliforme strains. The leukotoxin operon of F. necrophorum
      consists of three genes (lktBAC) of which the leukotoxin structural gene (lktA)
      is the second gene in the operon. In this study, the promoter regions of the
      leukotoxin operons from the two subspecies were identified and their nucleotide
      sequence compared. The promoter regions were found to differ in sequence, in
      length of the sequence between the upstream determinant (oppF) and the first gene
      of the leukotoxin operon (lktB), and in promoter strength as assayed in
      Escherichia coli host cells.

PMID- 16303264
TI  - The prevalence of methicillin-resistant staphylococci in healthy horses in the
      Netherlands.
AB  - Two hundred healthy horses housed at 23 different farms and one clinic and 42
      persons in close contact with these horses were screened for the presence of
      methicillin resistant staphylococci. Samples were taken from the nose and the
      pastern of the horses and from the nose and throat of the humans and incubated in
      selective media. Isolates were identified by standard techniques and their
      susceptibilities were tested using an agar diffusion method. Methicillin
      resistant strains were tested for the presence of the mecA gene by PCR. In 45
      horses (22.5%) and 15 humans (35.7%) mecA positive staphylococci were found. All
      isolates were coagulase negative staphylococci, except for one methicillin
      resistant Staphylococcus aureus isolated from a veterinarian. Staphylococcus
      sciuri was the predominant species found among the methicillin resistant
      staphylococci (MRS) in the horses, whereas S. epidermidis predominated in the
      humans. From the horses, often more than one species of MRS could be isolated,
      resulting in a total of 175 mecA positive equine isolates. The equine isolates
      were predominantly susceptible to most antimicrobials tested, whereas the human
      isolates showed more resistance. In conclusion, no methicillin-resistant
      Staphylococcus aureus was found in healthy horses in the Netherlands, but
      methicillin-resistant coagulase negative staphylococci were found frequently.
      Further studies are needed in order to investigate whether horses can be a
      reservoir for MRS or the mecA gene for humans.

PMID- 16303265
TI  - Proceedings of EUROTOX 2005, the 42nd Congress of the Association of European
      Toxicologists and European Societies of Toxicology. September 11-14, 2005.
      Cracow, Poland.

PMID- 16303266
TI  - Sperm binding, in vitro fertilization, and in vitro embryonic development of
      bovine oocytes fertilized with spermatozoa incubated with norepinephrine.
AB  - The final stages of sperm maturation, fertilization, and early embryonic
      development occur within the oviduct and are essential for successful
      reproduction in mammals. Norepinephrine was previously identified in native
      bovine oviductal fluid and its in vitro effects on bull sperm capacitation and
      the acrosome reaction have been determined. It was unknown how physiological
      concentrations of norepinephrine influence sperm binding, fertilization, and
      embryo development. Therefore, the objective of this study was to determine if
      pre-incubating bovine spermatozoa with physiological concentrations of
      norepinephrine prior to insemination of bovine oocytes would improve sperm-oocyte
      binding, fertilization, and embryonic development in vitro. Norepinephrine, in
      concentrations representing those measured in bovine oviductal fluid, was used to
      treat bovine spermatozoa prior to insemination. Spermatozoa incubated in
      norepinephrine were used to inseminate bovine oocytes matured in vitro, and
      oocytes were evaluated for sperm binding and fertilization. Additional
      experiments were conducted to evaluate how early in the co-incubation period
      oocytes were fertilized by spermatozoa pre-incubated with norepinephrine, and to
      test the developmental competence of those oocytes fertilized with norepinephrine
      treated sperm. Sperm binding to the zona pellucida was reduced by pre-incubation
      with norepinephrine. Rates of fertilization and embryo development did not
      increase as a result of pre-incubating spermatozoa with norepinephrine, but as
      early as 4h after insemination, spermatozoa treated with 20 ng/ml norepinephrine
      fertilized more oocytes than spermatozoa incubated in medium alone.
      Interestingly, this concentration of norepinephrine was found to capacitate
      spermatozoa in previous studies. These data suggest that oocytes fertilized by
      spermatozoa incubated in 20 ng/ml norepinephrine fertilize earlier in vitro than
      sperm pre-incubated in medium alone, and provide additional support for the role
      of norepinephrine in sperm capacitation and the acrosome reaction.

PMID- 16303267
TI  - Factors associated with treatment options among menopausal women in Taiwan.
AB  - OBJECTIVES: Taiwan has a two-tiered medical system that includes modern medicine
      and traditional Chinese medicine (TCM). The objectives of this study were to
      compare the characteristics of menopausal women who did not use any treatment,
      who used hormone replacement therapy (HRT), and who used TCM to treat their
      climacteric symptoms. METHODS: The study subjects were 182 women aged 46-55 years
      (non-treatment: 61, HRT: 60, TCM: 61). Variables used included socio
      demographics, climacteric symptoms, other physical symptoms, experiences with the
      treatment, and attitude toward menopause. Multivariate analyses were performed
      using multinomial logistic regression. RESULTS: Compared with women in the non
      treatment group, employed women were more likely to have received HRT or TCM.
      Women in the TCM group were more likely to have comorbid non-climacteric physical
      symptoms and were less likely to have family support for the use of HRT. Women in
      the TCM group were more likely to have an attitude regarding menopause as a
      natural phenomenon and as having little impact on attractiveness and sexual life.
      Severity of current climacteric symptoms was lower in the HRT group, while it was
      higher in the TCM group. These factors accounted for 66.1% of the model
      variances. CONCLUSIONS: Women in different treatment groups had different
      characteristics. Health professionals should be aware of the differences and
      provide information on treatment options in order to help and support women in
      making treatment decisions.

PMID- 16303268
TI  - Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles.
AB  - The process of opsonization is one of the most important biological barriers to
      controlled drug delivery. Injectable polymeric nanoparticle carriers have the
      ability to revolutionize disease treatment via spatially and temporally
      controlled drug delivery. However, opsonin proteins present in the blood serum
      quickly bind to conventional non-stealth nanoparticles, allowing macrophages of
      the mononuclear phagocytic system (MPS) to easily recognize and remove these drug
      delivery devices before they can perform their designed therapeutic function. To
      address these limitations, several methods have been developed to mask or
      camouflage nanoparticles from the MPS. Of these methods, the most preferred is
      the adsorption or grafting of poly(ethylene glycol) (PEG) to the surface of
      nanoparticles. Addition of PEG and PEG-containing copolymers to the surface of
      nanoparticles results in an increase in the blood circulation half-life of the
      particles by several orders of magnitude. This method creates a hydrophilic
      protective layer around the nanoparticles that is able to repel the absorption of
      opsonin proteins via steric repulsion forces, thereby blocking and delaying the
      first step in the opsonization process.

PMID- 16303269
TI  - Monitoring the ingestion of anti-tuberculosis drugs by simple non-invasive
      methods.
AB  - This investigation retrospectively assessed inexpensive non-invasive qualitative
      methods to monitor the ingestion of anti-tuberculosis drugs isoniazid, rifampicin
      and rifapentine. Results showed that commercial test strips detected the
      isoniazid metabolites isonicotinic acid and isonicotinylglycine as efficiently as
      the isonicotinic acid method in 150 urine samples. The presence of rifamycins in
      urine samples (n=1085) was detected by microbiological assay techniques and the
      sensitivity compared to the n-butanol extraction colour test in 91 of these
      specimens. The proportions detected by the two methods were significantly
      different and the sensitivity of the n-butanol procedure was only 63.8% (95% CL
      51.2-76.4%) as compared to that of the superior microbiological method. Final
      validation (n=691) showed that qualitative assays measure isoniazid and rifamycin
      ingestion with an efficiency similar to high-performance liquid chromatography.
      The qualitative procedures may therefore be valuable in clinical trials and in
      tuberculosis clinics to confirm drug ingestion.

PMID- 16303270
TI  - In-line monitoring of partial and overall solid concentration during solvent
      mediated phase transition using Raman spectroscopy.
AB  - A calibration strategy for the continuous monitoring of solvent-mediated phase
      transition was developed using in situ Raman spectroscopy. Citric acid which
      exhibits enantiotropy during its anhydrous/monohydrate phase transition was
      selected as a model organic product. Using 25 samples in suspension, specific
      calibration of the spectral data was obtained for estimating in-line both the
      overall solid concentration in suspension and the composition of the solid phase.
      In addition to such key-measurements, reliable estimates of supersaturation were
      computed in-line from the mass balance of the solute. In order to validate the
      technique, anhydrous to monohydrate phase transition experiments were performed
      in suspensions at 15 degrees C and the kinetic process involved was monitored.
      Despite the use of various solid concentrations and reactor configurations, both
      the reproducibility and the reliability of the in situ Raman measurements are
      shown to be satisfactory.

PMID- 16303271
TI  - Anti-inflammatory activity of Trichodesma indicum root extract in experimental
      animals.
AB  - The chloroform extract of Trichodesma indicum root has been evaluated for anti
      inflammatory activity against oedema produced by carrageenan, dextran, histamine
      and serotonin, and against formation of granulation tissues by cotton pellet in
      rats. The effect was compared with the activity of indomethacin, cyperoheptadine
      and dexamethasone against different types of inflammation. The chloroform extract
      at doses of 50, 100 and 200 mg/kg exhibited significant (P < 0.001) anti
      inflammatory activity in acute and chronic inflammatory models. At 200 mg/kg the
      chloroform extract showed maximum inhibition of 48.12% in carrageenan-induced rat
      paw oedema while the standard indomethacin inhibited it by 54.32% after 3 h of
      carrageenan injection. The chloroform extract (50, 100 and 200 mg/kg)
      significantly (P < 0.001) and dose-dependently inhibited dextran, histamine and
      serotonin-induced rat paw oedema compared with control group (vehicle-treated).
      In the chronic inflammatory model, the chloroform extract (100 and 200 mg/kg)
      inhibited the granuloma weight by 15.42 and 21.12%, respectively, whereas the
      indomethacin and dexamethasone inhibited it by 29.29 and 34.13%, respectively.
      The results obtained suggest marked anti-inflammatory activity of the extract at
      the dose levels examined.

PMID- 16303272
TI  - Effects of seasonal variation on the central nervous system activity of Ocimum
      gratissimum L. essential oil.
AB  - Ocimum gratissimum L. (Lamiaceae) and other species of the same genus are used as
      medicines to treat central nervous system (CNS) diseases, commonly encountered in
      warm regions of the world. The chemical composition of Ocimum gratissimum
      essential oil varies according to their chemotypes: timol, eugenol or geraniol.
      In this study, the essential oil type eugenol was extracted by hydrodistillation
      in each of the four seasons of the year. Activity upon CNS was evaluated in the
      open-field and rota-rod tests; sleeping time induced by sodium pentobarbital
      (PBS, 40 mg/kg, intra-peritoneally, i.p.) and anticonvulsant activity against
      seizures induced by both pentylenetetrazole (PTZ; 85 mg/kg, s.c.) and maximal
      electroshock (MES, 50 mA, 0.11 s) were determined. Essential oils obtained in
      each season were effective in increasing the sleeping duration and a preparation
      obtained in Spring was able to protect animals against tonic seizures induced by
      electroshock. In each season, eugenol and 1,8-cineole were the most abundant
      compounds, and in Spring the essential oil presented the greatest relative
      percentage of sesquiterpenes, suggesting that these compounds could explain the
      differences observed in the biological activity in essential oils obtained in
      different seasons of the year.

PMID- 16303273
TI  - Quantitative determination of insulin entrapment efficiency in triblock
      copolymeric nanoparticles by high-performance liquid chromatography.
AB  - A rapid and effective isocratic chromatographic procedure was described in this
      paper for the determination of insulin entrapment efficiency (EE) in triblock
      copolymeric nanoparticles using reversed-phase high-performance liquid
      chromatography (RP-HPLC) with an ultraviolet/visible detector at low flow rate.
      The method has been developed on a Shimadzu Shim-pack VP-ODS column (150 mm x 4.6
      mm, 5 microm, Chiyoda-Ku, Tokyo, Japan) using a mixture of 0.2 M sodium sulfate
      anhydrous solution adjusted to pH 2.3 with phosphoric acid and acetonitrile
      (73:27, v/v) as mobile phase at the flow rate of 0.8 ml min(-1) and a 214 nm
      detection. The method was validated in terms of selectivity, linearity,
      precision, accuracy, solution stability, limit of detection (LOD) and limit of
      quantification (LOQ). The calibration curve was linear in the concentration range
      of 2.0-500.0 microg ml(-1), and the limits of detection and quantitation were 8
      and 20 ng, respectively. The mean recovery of insulin from spiked samples, in a
      concentration range of 8-100 microg ml(-1), was 98.96% (R.S.D.= 2.51%, n = 9).
      The intra- and inter-assay coefficients of variation were less than 2.24%. The
      proposed method has the advantages of simple pretreatment, rapid isolation, high
      specificity and precision, which can be used for direct analysis of insulin in
      commercially available raw materials, formulations of nanoparticles, and drug
      release as well as stability studies.

PMID- 16303274
TI  - Determination of salbutamol in syrups by capillary electrophoresis with
      contactless conductivity detection (CE-C(4)D).
AB  - This paper describes the separation and quantification of salbutamol in
      pharmaceutical products (salbutamol syrups) by capillary electrophoresis (CE)
      with contactless conductivity detection (C(4)D). The system was studied by
      micellar electrokinetic capillary chromatography (MEKC) and free solution
      capillary electrophoresis (FSCE), being the latter chosen in function of best
      resolution and sensitivity in comparison with the MEKC method. CE-C(4)D was
      applied to analysis of salbutamol in syrups utilizing 1.0 x 10(-2) molL(-1)
      acetic acid/sodium acetate buffer (pH 4.9) as running electrolyte.
      Tetraethylammonium (TEA) solution was used as internal standard. The results
      obtained include a linear dynamic range from 7. x 10(-5) to 3.0 x 10(-4) molL(-1)
      and good repeatability (R.S.D.=4.7% for n=10 for a 7.0 x 10(-5) molL(-1)
      salbutamol solution). The detection limit was calculated as 1.0 x 10(-5) molL(-1)
      and the limit of quantification was estimated as 3.3 x 10(-5) molL(-1). For
      syrups analysis the reproducibility presented deviations between 1.5% and 2.5%
      (three different days) obtained for measurements in triplicate.

PMID- 16303275
TI  - Method development for the enantiomeric purity determination of low
      concentrations of adrenaline in local anaesthetic solutions by capillary
      electrophoresis.
AB  - L-adrenaline is often included in local anaesthetic (LA) solutions for injection
      to improve the quality of the anaesthetic block. The concentration of the LA is
      between 2.5 and 20 mg/ml and the concentration of adrenaline is typically < or =
      0.1% of the LA concentration. In order to follow the racemization into d
      adrenaline, not only is chiral separation needed but also sufficient resolution
      from the LA and other components of the injection solution. Furthermore, very
      high sensitivity is needed in order to be able to determine the d-enantiomer at
      very low concentrations, i.e. down to about 0.1 microg/ml. The development of a
      chiral capillary electrophoresis method that is able to determine the
      racemization of adrenaline is described, together with a limited validation.
      Samples are injected without pretreatment and analysed with a capillary
      electrophoresis buffer containing 40 mM heptakis(2,6-di-O-methyl)-beta
      cyclodextrin, 0.10 M phosphoric acid and 0.05 M triethanolamine. The amounts of d
      adrenaline found in the LA products tested were typically < 3% of the l
      adrenaline concentration and < 0.003% of the LA concentration.

PMID- 16303276
TI  - Amodiaquine polymeric membrane electrode.
AB  - The construction and electrochemical response characteristics of two types of
      poly(vinyl chloride) (PVC) membrane sensors for the determination of amodiaquine
      hydrochloride (ADQ.2HCl) are described. The sensing membrane comprised an ion
      pair formed between the cationic drug and sodium tetraphenyl borate (NaTPB) or
      potassium tetrakis(4-chlorophenyl) borate (KTCPB) in a plasticized PVC matrix.
      Eight PVC membrane ion-selective electrodes were fabricated and studied. Several
      plasticizers were studied namely, dioctyl phthalate (DOP), 2-nitrophenyl octyl
      ether (NPOE), dioctyl phenylphosphonate (DOPP) and bis(2-ethylhexyl)adipate
      (EHA). The sensors display a fast, stable and near-Nernstian response over a
      relative wide ADQ concentration range (3.2 x 10(-6) to 2.0 x 10(-2) M), with
      slopes comprised between 28.5 and 31.4 mV dec(-1) in a pH range comprised between
      pH 3.7 and 5.5. The assay of amodiaquine hydrochloride in pharmaceutical dosage
      forms using one of the proposed sensors gave average recoveries of 104.3 and 99.9
      with R.S.D. of 0.3 and 0.6% for tablets (Malaritab) and a reconstituted powder
      containing ADQ.2HCl, respectively. The sensor was also used for dissolution
      profile studies of two drug formulations. The sensor proved to have a good
      selectivity for ADQ.2HCl over some inorganic and organic compounds, however,
      berberine chloride interfered significantly. The results were validated by
      comparison with a spectrophotometric assay according to the USP pharmacopoeia.

PMID- 16303277
TI  - Official USP Reference Standards: metrology concepts, overview, and scientific
      issues and opportunities.
AB  - The United States Pharmacopeia (USP) is a private standards-setting body created
      in 1820 by practitioners who wished to promote the quality of therapeutic
      products in commerce. The principal product of USP, then and now, is the United
      StatesPharmacopeia (USP), to which was added the National Formulary (NF) in 1975.
      The two compendia are published as a combined text annually (USP-NF). Originally
      a book of process standards, USP-NF evolved over time into compendia containing
      primarily product standards that are expressed in monographs for therapeutic
      ingredients, products, and excipients. As a public health service, USP supplies
      official USP Reference Standards to manufacturers and others who wish to test an
      article according to selected procedures of a monograph or General Chapter.
      During the past decade, understanding of USP monographs and official USP
      Reference Standards as a means of controlling the quality of a therapeutic
      article has evolved, based on advances in metrology, on activities in the
      International Conference on Harmonization of Technical Requirements for the
      Registration of Pharmaceuticals for Human Use (ICH), and on considerations by the
      USP Council of Experts and its Expert Committees and USP staff. This article
      discusses the evolution of this understanding, focusing on drug substances and
      excipients for well-characterized small molecules and their corresponding dosage
      forms.

PMID- 16303278
TI  - Exogenous leptin advances puberty in domestic hen.
AB  - The present study was undertaken to examine the effect of recombinant chicken
      leptin administered to fed ad libitum and feed-restricted immature chickens of a
      layer strain on ovarian development and the timing of sexual maturity. In the
      first experiment 11-week-old pullets (77 days of age) fed ad libitum were
      injected daily with leptin at four dose levels (4, 16, 64 and 256 microg/kg body
      weight) until sexual maturity (lay of the first egg). Leptin treatment at the
      highest dose significantly (P<0.05) advanced the onset of puberty (day 116.3+/
      1.0) in comparison to controls (day 121.3+/-1.2). The rises of luteinizing
      hormone, estradiol and progesterone in blood plasma were also advanced by leptin
      treatment. In the second experiment, both full-fed and feed-restricted pullets
      (79 days of age) were injected daily with leptin (256 microg/kg body weight). In
      birds fed ad libitum, exogenous leptin again significantly (P<0.05) advanced
      first ovipostion (day 118.4+/-1.4 versus day 124.4+/-1.7), while abolishing the
      significant (P<0.05) delay caused by feed restriction (day 131.5+/-1.6) and
      restoring the normal onset of sexual maturity (day 125.7+/-1.6). Analysis of the
      ovaries in 106-day-old pullets revealed that leptin injections advanced
      follicular development, particularly in birds fed ad libitum, and significantly
      (P<0.01) reduced follicular apoptosis both in full-fed and feed-restricted birds.
      In conclusion, we have shown that in female chickens exogenous leptin advances
      the onset of puberty by attenuation of ovarian apoptosis and enhancement of
      folliculogenesis.

PMID- 16303279
TI  - A cooperative action of endothelin-1 with prostaglandin F(2alpha) on luteal
      function in the cow.
AB  - Prostaglandin F(2alpha) (PGF(2alpha)) is the primary luteolysin in the cow, and
      luteal endothelin-1 (ET-1) interacts with PGF(2alpha) during the process of
      luteolysis. In contrast, a developing corpus luteum (CL) is refractory to
      exogenous administration of PGF(2alpha). Thus, the present study was aimed to
      investigate the functional relationship between ET-1 and PGF(2alpha) in the mid
      CL (PGF(2alpha)-sensitive) and early-CL (PGF(2alpha)-refractory). In the mid-CL
      model, cows (n = 6/treatment) were assigned to receive one of five types of
      treatments on day 10 of the estrous cycle: (1) an injection of saline; control,
      (2) a 500 microg of PGF(2alpha) analogue (sufficient dose to induce luteolytis);
      full-PG, (3) an intraluteal injection of 0.25 mg ET-1; ET-1, (4) a 125 micro g of
      PGF(2alpha) (insufficient dose to induce luteolytis); 1/4PG or (5) an intraluteal
      injection of 0.25 mg ET-1 after administration of a insufficient dose of
      PGF(2alpha) analogue; 1/4PG/ET. In the early-CL model, cows were assigned to
      receive one of two types of treatments on day 5 of the estrous cycle: (1) a
      sufficient dose of PGF(2alpha) analogue; PG (n = 5) or (2) an intraluteal
      injection ET-1 after a sufficient dose of PGF(2alpha); PG/ET (n = 7). In the mid
      CL model, 1/4PG/ET resulted in a rapid reduction of progesterone (P)
      concentrations similar to that in full-PG from the next day. However, the levels
      of P in 1/4PG/ET (1.5-2.5 ng/ml) kept significantly higher than that in full-PG
      (< 0.5 ng/ml). ET-1 or 1/4PG did not decrease plasma P concentrations (4-6
      ng/ml). The plasma ET-1 levels increased with the full-PG administration. In the
      early-CL model, both treatments had no effect on plasma P increase and ET-1
      levels. The overall results indicate that the intraluteal ET-1 injection after
      administration of insufficient dose of PGF(2alpha) induces the depression of P
      secretion in vivo during the mid luteal phase in the cow, supporting the concept
      that ET-1 is one of a local mediator of functional luteolysis in the cow. The
      result further indicates that the early-CL is not only PG-refractory but also ET
      1-refractory.

PMID- 16303280
TI  - Discrepancy between second and first opinion in surgical oncological patients.
AB  - PURPOSE: To prospectively describe in a population of oncological second opinion
      patients: (1) the outcome of routine revisions of histopathological and
      radiological material, (2) the frequency and extent of discrepancy between the
      second and first opinion and (3) the location of further treatment or follow-up.
      PATIENTS AND METHODS: In a population of 466 consecutive patients seeking a
      second opinion at the Surgical Oncology Outpatient Clinic, demographic and
      clinical patient characteristics were registered prospectively, as were the
      results of routine revision of histopathological and radiological material and
      the location of further treatment or follow-up. A classification system was
      developed to categorize the differences between the second and first opinion.
      RESULTS: The mean age of the 403 eligible patients was 52 years. Most patients
      (87%) were women, of whom 83% were diagnosed with breast cancer. Revision of
      histopathological and radiological material was performed in 80 and 61% of the
      cases, respectively, and resulted in a major change in treatment or prognosis in
      3 and 2% of patients, respectively. In 317 patients (79%), the second opinion
      could be compared with the first opinion, resulting in an identical advise in
      68%, a minor discrepancy in 16% and a major discrepancy in another 16% of
      patients. For further treatment 78% of patients were referred back to their first
      specialist. CONCLUSION: One third of patient-initiated second opinion
      consultations resulted in a discrepancy with the first opinion. Half of these
      different advise lead to major changes in therapy or prognosis.

PMID- 16303281
TI  - Toxicity and mortality of cytoreduction and intraoperative hyperthermic
      intraperitoneal chemotherapy in pseudomyxoma peritonei--a report of 103
      procedures.
AB  - AIMS: To report on treatment related toxicity and mortality in patients with
      pseudomyxoma peritonei (PMP) treated by cytoreduction in combination with
      intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and to identify
      prognostic factors. METHODS: A review was performed of 103 procedures of
      cytoreduction and intraoperative HIPEC for PMP between 1996 and 2004. Toxicity
      was graded according to the National Cancer Institute Common Toxicity Criteria
      (NCI CTC) classification. A surgical complication was defined as any post
      operative event that needed re-intervention. Pre and peroperative factors were
      studied on their relationship to toxicity and mortality. RESULTS: The median
      hospital stay was 21 days (4-149) with a treatment related toxicity of 54% and a
      30 days mortality of 3%. In univariate analysis, toxicity was associated with
      abdominal tumour load (p<0.01), completeness of cytoreduction (p<0.01), and age
      (p=0.05). Surgical complications, mainly small bowel perforations/suture leaks,
      were the main cause of toxicity. A favourable pathology decreased mortality.
      CONCLUSIONS: Cytoreduction in combination with intraoperative HIPEC in PMP
      patients is a treatment with a relatively high toxicity, but a considerable long
      term survival in selected patients. Toxicity is mainly surgery related.
      Concentration of cases to acquire sufficient experience and better selection on
      age, pathology, and extent of disease is essential to reduce treatment related
      toxicity and mortality.

PMID- 16303282
TI  - Differentiation of obsessive-compulsive-, panic-, obsessive-compulsive
      personality-, and non-disordered individuals by variation in the promoter region
      of the serotonin transporter gene.
AB  - Past research investigating the role of the serotonin transporter gene in OCD has
      produced mixed findings. One possible reason for the mixed findings is
      comorbidity. In this study, non-comorbid OCD individuals were compared to non
      disordered controls. A sample of panic disordered individuals was also compared
      to a non-disordered group. Finally, as an exploratory analysis, individuals were
      assessed for OCPD and their allelic frequencies were also compared to non
      disordered individuals. Analyses revealed that there were higher frequencies of
      the s/s genotype among the OCD group when compared to non-disordered controls.
      There were no differences in allelic frequencies on the serotonin transporter
      gene between the panic disordered group, the OCPD group, and the non-disordered
      control group. This study found that non-comorbid OCD individuals tended to have
      a higher percentage of the homozygous short genotype than non-disordered
      individuals. The s/s genotype might serve as a contributory risk factor for OCD.

PMID- 16303283
TI  - Different classes of tissue-specific genes show different levels of noncoding
      conservation.
AB  - We divide tissue-specific genes into two major classes: regulators, defined as
      genes participating in tissue-specific transcriptional regulation, and effectors,
      defined as genes involved in rendering the physiological properties of cells. We
      show that regulators tend to have significantly greater noncoding conservation
      than effectors. We further show that within the regulator class, tissue-specific
      transcription factors generally have the greatest noncoding conservation, whereas
      signal receptors generally have the least noncoding conservation. Using noncoding
      conservation as a proxy for the complexity of cis-regulatory DNA, we extrapolate
      that different classes of tissue-specific genes tend to have different levels of
      cis-regulatory complexity and that greater complexity can be found in genes
      involved in transcriptional regulation, especially transcription factors.

PMID- 16303284
TI  - Expression and transcriptional control of human KCNE genes.
AB  - Potassium channels are essential for a variety of cellular processes ranging from
      membrane excitability to cellular proliferation. The KCNE genes (KCNE1-5) encode
      a family of single-transmembrane-domain proteins that modulate the properties of
      several potassium channels, suggesting a physiologic role for these accessory
      subunits in many human tissues. To investigate the expression and transcriptional
      control of KCNE genes we mapped transcription start sites, delineated 5' genomic
      structure, and characterized functional promoter elements for each gene. We
      identified alternatively spliced transcripts for both KCNE1 and KCNE3, including
      a cardiac-specific KCNE1 transcript. Analysis of relative expression levels of
      KCNE1-5 in a panel of human tissues revealed distinct, but overlapping,
      expression patterns. The coexpression of multiple functionally distinct KCNE
      genes in some tissues infers complex accessory subunit modification of potassium
      channels. Identification of the core promoter elements necessary for
      transcriptional control of the KCNE genes facilitates future work investigating
      factors responsible for tissue-specific expression as well as the discovery of
      promoter variants associated with disease.

PMID- 16303285
TI  - Testicular toxicity of DEHP, but not DEHA, is elevated under conditions of
      thioacetamide-induced liver damage.
AB  - As part of an investigation of possible enhancement by liver disease of
      testicular toxicity caused by phthalates, we tested the effects of di(2
      ethylhexyl)phthalate (DEHP) and di(2-ethylhexyl)adipate (DEHA) in a thioacetamide
      (TAA)-induced rat liver damage model. Male, 6-week-old, F344 rats (n=60) were
      divided into ten groups. Animals of groups 1-5 received TAA (200 mg/kg,
      intraperitoneal, three times per week) for 4 weeks, and groups 6-10 served as
      controls without TAA. After a 1 week interval, at week 5, powder diet containing
      DEHP or DEHA was provided to the animals of groups 1 and 6 (DEHP 25000 ppm),
      groups 2 and 7 (DEHP 6000 ppm), groups 3 and 8 (DEHA 25000 ppm) and groups 4 and
      9 (DEHA 6000 ppm), while groups 5 and 10 received basal diet. All animals were
      sacrificed at week 9. Significant decrease in sperm numbers and motility and
      increase in morphology abnormalities were evident in group 1 as compared to
      groups 5 and 6 (p<0.01). However, DEHA treatment was not associated with any
      apparent testicular toxicity in either TAA- or vehicle-treated animals.
      Histopathological examination of the testes revealed severe atrophy and
      degeneration of testicular tubules in all animals given TAA and DEHP at high
      dose, only mild to moderate lesions being found with DEHP alone. We conclude that
      liver toxicity induced by TAA is associated with the enhancement of testicular
      toxicity of DEHP, but not DEHA, in rats.

PMID- 16303286
TI  - Metallothionein-I-II expression in young and adult bovine pineal gland.
AB  - Aging is characterized, among other features, by an increased concentration of
      metal ions in the brain that may contribute to a greater increase in free
      radicals production. The present paper reports data regarding the concentration
      of some relevant metal ions (Cu, Fe, Mn, Zn), as well as the immunopositivity of
      metallothionein-I-II and GFAP in the bovine pineal gland with respect to animal
      aging. The pineal gland of young bovines displays several immunoreactive
      metallothionein-I-II positive elements in the parenchyma, whose number decreases
      with age. We also report that a well defined group of neurons bordering the third
      ventricle and located close to the subcommissural organ shows an intense
      metallothionein-I-II immunopositivity. The presence of metallothionein-I-II was
      confirmed by means of liquid chromatography coupled to tandem mass spectrometry.
      In particular, it proved possible to identify the amino acid sequences of the
      unique tryptic peptide not containing cysteine and two pepsin fragments
      containing cysteines. In conclusion, our data suggest the presence of a
      metallothionein-I-II expressing system in the pineal gland and ventricle-adjacent
      areas of the bovine epithalamus might possibly be related to the anti-aging
      effects of melatonin.

PMID- 16303287
TI  - Differential expression of ADAMTS-1, -4, -5 and TIMP-3 in rat spinal cord at
      different stages of acute experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an animal model of
      inflammatory demyelination, a pathological event common to multiple sclerosis
      (MS). During CNS inflammation there are alterations in the extracellular matrix
      (ECM). A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS)-1,
      -4 and -5 are proteases present in the CNS, which are able to cleave the
      aggregating chondroitin sulphate proteoglycans, aggrecan, phosphacan, neurocan
      and brevican. It is therefore important to investigate changes in their
      expression in different stages of EAE induction. We have investigated expression
      of ADAMTS-1, -4, -5 and tissue inhibitor of metalloproteinase (TIMP)-3, by real
      time RT-PCR. We have also examined protein expression of ADAMTS-1, -4 and -5 by
      western blotting and immunocytochemistry in spinal cord from animals at different
      stages of disease progression. Our study demonstrated a decrease in ADAMTS-4 mRNA
      and protein expression. TIMP-3 was decreased at the mRNA level although protein
      levels were increased in diseased animals compared to controls. Our study
      identifies changes in ADAMTS expression during the course of CNS inflammation
      which may contribute to ECM degradation and disease progression.

PMID- 16303288
TI  - beta-TrCP binding and processing of NF-kappaB2/p100 involve its phosphorylation
      at serines 866 and 870.
AB  - Processing of the NF-kappaB2 precursor protein p100 is a major step in
      noncanonical NF-kappaB signaling. This signaling step requires the NF-kappaB
      inducing kinase (NIK) and its downstream kinase, IkappaB kinase alpha (IKKalpha).
      We show here that p100 undergoes phosphorylation at serines 866, 870, and
      possibly 872, in cells stimulated with noncanonical NF-kappaB stimuli or
      transfected with NIK and IKKalpha. Phosphorylation of this serine cluster creates
      a binding site for beta-TrCP, the receptor subunit of the beta-TrCP(SCF)
      ubiquitin ligase. Mutation of either serine 866 or serine 870 abolishes the beta
      TrCP recruitment and ubiquitination of p100. The functional significance of p100
      phosphorylation is further supported by the finding that this molecular event
      occurs in a NIK- and IKKalpha-dependent manner. Additionally, induction of p100
      phosphorylation can be blocked by a protein synthesis inhibitor, suggesting the
      requirement of de novo protein synthesis. These data suggest that p100 processing
      involves its phosphorylation at specific terminal serines, which form a binding
      site for beta-TrCP thereby regulating p100 ubiquitination.

PMID- 16303289
TI  - Cysteine cathepsins in human silicotic bronchoalveolar lavage fluids.
AB  - Mature, active cysteine cathepsins (CPs) were identified in human inflammatory
      bronchoalveolar lavage fluid (BALF) supernatants from patients suffering from
      silicosis by both western blot and surface plasmon resonance analyses. BALFs are
      not a reservoir of activatable proforms, since no autocatalytic maturation at
      acidic pH occurs. Cathepsin H is the most profuse among studied CPs (median
      value: 36.5 nM), while cathepsins B and L are the two most abundant thiol
      dependent endoproteases. The overall concentration of active cathepsins B, H, K,
      L, and S is approximately 10-fold lower than their concentration in BALF
      supernatants from patients suffering from inflammatory acute lung injuries (962+/
      347 nM).The cathepsins (approximately 70 nM)/cystatin-like inhibitors
      (approximately 9 nM) ratio is unbalanced in favor of enzymes ( approximately 8
      fold). This presence of uncontrolled CPs suggests that they may contribute, in
      addition to matrix metalloproteases, to the lung tissue breakdown/remodeling
      occurring during silicosis, although their exact contribution to interstitial
      inflammation remains to be evaluated.

PMID- 16303290
TI  - Individual differences in brain activity during visuo-spatial processing assessed
      by slow cortical potentials and LORETA.
AB  - Using slow-cortical potentials (SCPs), Vitouch et al. demonstrated that subjects
      with low ability to solve a complex visuo-spatial imagery task show higher
      activity in occipital, parietal and frontal cortex during task processing than
      subjects with high ability. This finding has been interpreted in the sense of the
      so-called "neural efficiency" hypothesis, which assumes that the central nervous
      system of individuals with higher intellectual abilities is functioning in a more
      efficient way than the one of individuals with lower abilities. Using a higher
      spatial resolution of SCP recordings, and by employing the source localization
      method of LORETA (low-resolution electromagnetic tomography), we investigated
      this hypothesis by performing an extended replication of Vitouch et al.'s study.
      SCPs during processing of a visuo-spatial imagery task were recorded in pre
      selected subjects with either high or low abilities in solving the imagery task.
      Topographic and LORETA analyses of SCPs revealed that a distributed network of
      extrastriate occipital, superior parietal, temporal, medial frontal and
      prefrontal areas was active during task solving. This network is well in line
      with former studies of the functional neuroanatomy of visuo-spatial imagery.
      Contrary to our expectations, however, the results of Vitouch et al. as well as
      of other studies supporting the neural efficiency hypothesis could not be
      confirmed since no difference in brain activity between groups was observed. This
      inconsistency between studies might be due to differing task processing
      strategies. While subjects with high abilities in the Vitouch et al. study seemed
      to use a visuo-perceptual task solving approach, all other subjects relied upon a
      visuo-motor task processing strategy.

PMID- 16303291
TI  - Choleretic effects of yarrow (Achillea millefolium s.l.) in the isolated perfused
      rat liver.
AB  - Different species from the Achillea millefolium aggregate are used against
      gastrointestinal and hepato-biliary disorders in traditional European medicine.
      In this work, a fraction enriched in dicaffeoylquinic acids (DCCAs) and luteolin
      7-O-beta-D-glucuronide was investigated on its choleretic effect in the isolated
      perfused rat liver (IPRL) compared to cynarin (1,3-DCCA), the main choleretic
      compound of Cynara scolymus L. A fraction containing 3,4-, 3,5- and 4,5-DCCA and
      luteolin-7-O-beta-D-glucuronide was prepared by solid phase extraction from a 20%
      methanolic extract of yarrow. A total amount of 48.8% DCCAs and 3.4% luteolin-7-O
      beta-D-glucuronide was determined by HPLC analysis with cynarin as internal
      standard. IPRL experiments revealed a dose-dependant increase in bile flow (23-44
      47%) by the Achillea fraction. Choleresis was two- to three-fold higher than that
      of cynarin. The combined effect of DCCAs and luteolin-7-O-beta-D-glucuronide
      stimulated bile flow more effectively than the single compound cynarin. Due to
      their polar structure, these compounds are quantitatively extracted into teas and
      tinctures; hence, they seem to be the choleretic active principles in the
      traditional application forms of yarrow.

PMID- 16303293
TI  - Short- and long-term outcome of lung volume reduction surgery. The predictive
      value of the preoperative clinical status and lung scintigraphy.
AB  - The NETT study assessed the benefits of lung volume reduction surgery (LVRS)
      versus medical treatment. However, data is available only on the early outcome of
      LVRS (24 months). We evaluate the factors affecting the outcome at one-year and
      up to 6 years after LVRS. Thirty-seven patients underwent LVRS. Thirty-five
      patients, who survived the operation for at least one-year, were followed up to 6
      years. Patients' laboratory, clinical and scintigraphic data before surgery were
      reviewed retrospectively, and follow-up at one-year and at the end of data
      collection. Successful LVRS with improvement of FEV(1)30% at one-year was
      observed in 13 of 35 patients. Five of these patients had initial FEV(1) values
      of <20% of the predicted. The group of patients with improvement was younger as
      compared to the 22 patients without improvement (P<0.005). The younger age group
      used less supplemental oxygen and had a PDiff of >23%. Combinations of age under
      60 years and PDiff >23% were a favorable factor (P<0.002) for successful LVRS.
      Thirty-four patients were followed up to 6 years. Fifteen of the 34 patients
      (44.1%) remained well. Use of supplemental oxygen before surgery, and FEV(1)
      improvement of 30% at one-year after surgery were good prognostic factors. We
      concluded that the long-term success of LVRS is affected by non-dependence on
      oxygen supplementation before surgery, and the one-year post-surgical improvement
      of FEV(1) (30%). Based on our findings, the subgroup of patients below 60 years
      old with severe disease (FEV(1)<20%) and heterogeneous upper lobe emphysema
      (Pdiff>23%) has improved outcome.

PMID- 16303292
TI  - Recognition of tumor glycans by antigen-presenting cells.
AB  - C-type lectin receptors on antigen-presenting cells are potent antigen-uptake
      receptors with specificity for glycan structures. Glycosylation changes during
      malignant transformation create tumor-specific carbohydrate structures that
      interact with C-type lectins on dendritic cells. Recent findings revealed that
      tumor glycoproteins, such as carcinoembryonic antigen and MUC-1, indeed interact
      with the C-type lectins DC-SIGN and macrophage galactose-type lectin on antigen
      presenting cells. The consequences for anti-cancer immunity or tolerance
      induction can be extrapolated from the function of C-type lectins in pathogen
      recognition and antigen presentation. In addition, in vivo studies in mice
      recently demonstrated the potency of targeting antigens to C-type lectins on
      antigen-presenting cells for anti-tumor vaccination strategies.

PMID- 16303294
TI  - Defining and investigating difficult asthma: developing quality indicators.
AB  - BACKGROUND: There is no agreed definition of 'difficult asthma' or what
      investigations should be available to investigate these patients. Patients with
      difficult asthma remain symptomatic on high levels of treatment and are high
      users of medical resources. AIM: To develop a set of quality indicators for the
      definition and investigation of difficult asthma. METHOD: Modified RAND
      Appropriateness Method was used. An expert panel composed of nine hospital asthma
      specialists who run 'difficult' asthma clinics and were identified from a short
      list of key workers in the field. Indicators were rated as necessary to define
      and investigate difficult asthma. RESULTS: Difficult asthma was defined as
      'symptoms persisting beyond therapy consistent with step 4 of the British
      Thoracic Society (BTS) guidelines' (high dose inhaled corticosteroids and long
      acting beta(2)-agonists). Eighty-three indicators were identified (40 relating to
      definition and 43 relating to investigations). Of these 32 (39%) were rated as
      necessary: 7 out of 40 (18%) for defining difficult asthma and 23 out of 43 (53%)
      for investigations. Indicators of high medical resource usage were characteristic
      of the 'difficult' nature of the management of patient with difficult asthma. A
      framework for the investigation of these patients was created. CONCLUSION: The
      listed performance indicators identify a range of requirements that are necessary
      to define difficult asthma. Targeting of real needs in this group of patients
      will lead to better patient care and reduction of 'waste' in provision of
      healthcare.

PMID- 16303295
TI  - Safety and tolerability of high-dose formoterol (via Aerolizer) and salbutamol in
      patients with chronic obstructive pulmonary disease.
AB  - To evaluate the safety and tolerability of high-dose formoterol and salbutamol in
      patients with chronic obstructive pulmonary disease (COPD). In this two-way
      crossover, double-blind, double-dummy study, 17 adults with mild-to-moderate COPD
      were randomized to receive either formoterol 24 microg (2 x 12 microg via
      Aerolizer), or salbutamol 600 microg (6 x 100 microg via metered-dose inhaler),
      and the appropriate double-dummy q.i.d. at 4-h intervals for 3 consecutive days
      (total daily dose: 96 and 2400 microg, respectively). After a 4-7-day washout
      period, patients were switched to the other treatment. Treatment with high-dose
      formoterol and salbutamol was equally well tolerated, with no reports of serious
      adverse events. Both agents were associated with decreased plasma potassium (mean
      minimum values: 3.4 and 3.3 mmol/l for formoterol and salbutamol, respectively;
      P=0.914), increased serum glucose (mean maximum values: 9.0 and 8.7 mmol/l,
      respectively; P=0.373), and small increases in mean QTc interval (mean maximum
      439 ms with both treatments; P=0.813). No clinically relevant between-treatment
      differences in adverse events or laboratory values occurred. Both drugs improved
      lung function (mean maximum forced expiratory volume in 1s [FEV(1)] 2.6 l with
      both treatments; P=0.624), with the improvement being significantly greater with
      formoterol than with salbutamol on all 3 days of treatment (mean area under the
      curve [AUC](0-24 h) of FEV(1) formoterol vs. salbutamol on days 1-3, all P<0.05).
      High-dose formoterol via Aerolizer (up to 96 microg/day) has a comparable
      tolerability profile to that of salbutamol in patients with mild-to-moderate
      COPD.

PMID- 16303296
TI  - Noninvasive proportional assist ventilation and pressure support ventilation
      during arm elevation in patients with chronic respiratory failure. A preliminary,
      physiologic study.
AB  - BACKGROUND: It has been shown that upper limbs activity increases the respiratory
      workload in patients with chronic respiratory failure (CRF). The object of the
      present study was to investigate whether, in these patients: (i) noninvasive
      positive pressure ventilation (NPPV) could sustain the inspiratory muscles to
      meet the greater ventilatory demand during upper limbs activity with the arm
      elevation test (AE); (ii) proportional assist ventilation (PAV) might be superior
      to pressure support ventilation (PSV) during AE, because of its potential more
      adaptable response to sudden changes in the ventilatory pattern. METHODS: The
      study was performed in the pulmonary function laboratory of the Pulmonary
      Division in Verona General Hospital, Verona, Italy. We studied 8 male patients
      with CRF due to chronic obstructive pulmonary disease (COPD). Each patient
      received 2 treatment in random order with a crossover design: spontaneous
      breathing (SB), SB with AE, either PSV or PAV without and with AE, SB without and
      with AE, either PSV or PAV without and with AE. We measured: lung function tests,
      lung mechanics, ventilatory pattern and diaphragmatic effort (pressure time
      product, PTP(di)). RESULTS: (i) AE increases minute ventilation (+14%) and
      PTP(di) (+64%); (ii) ventilatory support, both with PSV and PAV unloads the
      diaphragm both at rest (PTP(di) -77% and -54%, respectively) and during arm
      elevation (PTP(di) -54% and -44%, respectively). CONCLUSIONS: PAV and PSV unloads
      the diaphragm in patients with CRF due to COPD both during SB and AE; PAV can be
      more efficient than PSV in assisting the diaphragm during AE in producing a
      greater level of minute ventilation for a similar rise in PTP(di) compared to
      PSV. Noninvasive ventilatory support should be considered in rehabilitation
      programs for training of upper limbs activity.

PMID- 16303297
TI  - Spatially controlled electro-stimulated DNA adsorption and desorption for biochip
      applications.
AB  - The manipulation of biomolecules at solid/liquid interfaces is important for the
      enhanced performance of a number of biomedical devices, including biochips. This
      study focuses on the spatial control of surface interactions of DNA as well as
      the electro-stimulated adsorption and desorption of DNA by appropriate surface
      modification of highly doped p-type silicon. Surface modification by plasma
      polymerisation of allylamine resulted in a surface that supported DNA adsorption
      and sustained cell attachment. Subsequent high-density grafting of poly(ethylene
      oxide) formed a low fouling layer resistant to biomolecule adsorption and cell
      attachment. Spatially controlled excimer laser ablation of the surface produced
      patterns of re-exposed plasma polymer with high-resolution. On patterned
      surfaces, preferential electro-stimulated adsorption of DNA to the allylamine
      plasma polymer surface and subsequent desorption by the application of a negative
      bias was observed. Furthermore, the concept presented here was investigated for
      use in transfection chips. Cell culture experiments with human embryonic kidney
      cells, using the expression of green fluorescent protein as a reporter,
      demonstrated efficient and controlled transfection of cells. Electro-stimulated
      desorption of DNA was shown to yield significantly enhanced solid phase
      transfection efficiencies to values of up to 30%. The ability to spatially
      control DNA adsorption combined with the ability to control the binding and
      release of DNA by application of a controlled voltage enables an advanced level
      of control over DNA bioactivity on solid substrates and lends itself to biochip
      applications.

PMID- 16303298
TI  - Enantioselective sensing of chiral amino acids by potentiometric sensors based on
      optical active polyaniline films.
AB  - A novel enantioselective potentiometric sensor was constructed based on optical
      active polyaniline (PAn) films. The sensor with high stability showed
      discrimination behavior toward one isomer of racemic phenylalanine (Phe). The (-)
      or (+) PAn-based electrodes exhibited an excellent Nernstian slope of
      approximately 60 mV per decade for L-Phe or D-Phe, respectively. In addition,
      when the sensor was exposed to the mixture of enantiomers, the slope of the
      response changed along with their proportions, which would be employed as an
      index of the enantiomeric purity of the mixture. At last, the mechanism of chiral
      discrimination for Phe was discussed.

PMID- 16303299
TI  - Effect of oral nitroethane and 2-nitropropanol administration on methane
      producing activity and volatile fatty acid production in the ovine rumen.
AB  - Strategies are sought to reduce economic and environmental costs associated with
      ruminant methane emissions. The effect of oral nitroethane or 2-nitropropanol
      administration on ruminal methane-producing activity and volatile fatty acid
      production was evaluated in mature ewes. Daily administration of 24 and 72 mg
      nitroethane/kg body weight reduced (P<0.05) methane-producing activity by as much
      as 45% and 69% respectively, when compared to control animals given no
      nitroethane. A daily dose of 120 mg 2-nitropropanol/kg body weight was needed to
      reduce (P<0.05) methane-producing activity by 37% from that of untreated control
      animals. Reductions in methane-producing activity may have been diminished by the
      last day (day 5) of treatment, presumably due to ruminal adaptation. Oral
      administration of nitroethane or 2-nitropropanol had little or no effect on
      accumulations or molar proportions of volatile fatty acids in ruminal contents
      collected from the sheep. These results demonstrate that nitroethane was superior
      to 2-nitropropanol as a methane inhibitor and that both nitrocompounds reduced
      ruminal methanogenesis in vivo without redirecting the flow of reductant
      generated during fermentation to propionate and butyrate.

PMID- 16303300
TI  - Pharmacokinetics and metabolism studies on (3-tert-butyl-7-(5-methylisoxazol-3
      yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy) pyrazolo[1,5-d][1,2,4]triazine, a
      functionally selective GABA(A) alpha5 inverse agonist for cognitive dysfunction.
AB  - (3-tert-Butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5
      ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine (1) was recently identified as a
      functionally selective, inverse agonist at the benzodiazepine site of GABA(A)
      alpha5 receptors and enhances performance in animal models of cognition. The
      routes of metabolism of this compound in vivo in rat have been well
      characterised, the identities of the major metabolites are confirmed by synthesis
      and their biological profiles were evaluated. An unusual oxidation of the
      pyrazolo[1,5-d][1,2,4]triazine core to the corresponding pyrazolo[1,5
      d][1,2,4]triazin-4(5H)-one scaffold by aldehyde oxidase has been observed.

PMID- 16303301
TI  - Synthesis of 2,5-thiazole butanoic acids as potent and selective alpha(v)beta3
      integrin receptor antagonists with improved oral pharmacokinetic properties.
AB  - We describe a series of 2,5 thiazole containing compounds, which are potent
      antagonists of the integrin alpha(v)beta3 and show selectivity relative to the
      other integrins, such as alpha(IIb)beta3 and alpha(v)beta6. These analogs were
      demonstrated to have high bioavailability relative to other relative heterocyclic
      analogs.

PMID- 16303302
TI  - Synthesis and in vitro antitubercular activity of some 1-[(4-sub)phenyl]-3-(4-{1
      [(pyridine-4-carbonyl)hydrazono]ethyl}phenyl)thiourea.
AB  - Various isonicotinyl hydrazones were prepared by reacting isonicotinyl hydrazide
      [INH] with 1-(4-acetylphenyl)-3-[(4-sub)phenyl]thiourea and were tested for their
      antimycobacterial activity in vitro against Mycobacterium tuberculosis H37Rv and
      INH-resistant M. tuberculosis using the BACTEC 460 radiometric system. Among the
      synthesized compounds, 1-(4-fluorophenyl)-3-(4-{1-[(pyridine-4-carbonyl)
      hydrazono]ethyl}phenyl)thiourea (4d) was found to be the most potent compound
      with a minimum inhibitory concentration of 0.49 microM against M. tuberculosis
      H37Rv and INH-resistant M. tuberculosis. When compared to INH, 4d was found to be
      3 and 185 times more active against M. tuberculosis H37Rv and INH-resistant M.
      tuberculosis, respectively, with a selectivity index of >300.

PMID- 16303303
TI  - Conformation stability and organization of mefloquine molecules in different
      environments.
AB  - The crystal structures of mefloquine base, [C17H16F6N2O], and two salts of
      mefloquine: hydrochloride [(C17H17F6N2O)+]3[Cl-]3.3H2O and hydrochloride
      tetrachlorocobaltate [(C17H17F6N2O)+]3Cl-[CoCl4]2-.C2H6O.H2O, were determined by
      X-ray diffraction measurements. A comparison of the crystal structures of
      mefloquine in three different crystalline environments shows that their
      conformations are stable regardless of mefloquine being a base or a salt. In
      addition, the conformation of mefloquine is similar to those of crystalline
      Cinchona alkaloids. The CF3 substituents in the quinoline moiety affect the
      packing of molecules.

PMID- 16303304
TI  - Thyroid receptor ligands. Part 4: 4'-amido bioisosteric ligands selective for the
      thyroid hormone receptor beta.
AB  - Based on the examination of the X-ray crystallographic structures of the LBD of
      TRalpha and TRbeta in complex with KB-141 (2), a number of novel 4'-hydroxy
      bioisosteric thyromimetics were prepared. Optimal affinity and beta-selectivity
      (33 times), was found with a medium-sized alkyl-substituted amido group; iso
      butyl (12c). It can be concluded that bioisosteric replacements of the 4'-hydroxy
      position represent a new promising class of TRbeta-selective synthetic
      thyromimetics.

PMID- 16303305
TI  - Do dynamic and static clinical measurements correlate with gait analysis
      parameters in children with cerebral palsy?
AB  - The present study documents the correlation between gait analysis data and
      clinical measurements and evaluates the combined predictive value of static and
      dynamic clinical measurements on gait data of children with cerebral palsy. Two
      hundred patients were evaluated using a set of measurements of range of motion
      (ROM), alignment, spasticity, strength and selectivity, and by three-dimensional
      gait analysis. Fair to moderate correlations were found between clinical
      measurements and gait data, the overall highest correlation being 0.60. Clinical
      data of strength and selectivity had the highest degree of significant
      correlations with gait data, compared to the ROM and spasticity. ROM, spasticity
      and strength measurements for the hip in the coronal plane and spasticity of
      rectus femoris most frequently showed fair to moderate correlations to gait data.
      Time and distance and EMG parameters mainly correlated with strength and
      selectivity parameters. Unexpectedly, alignment parameters only fairly correlated
      with hip rotation in stance. Multiple regression analysis revealed that adding
      dynamic clinical measurements (spasticity, strength and selectivity) to a static
      model (ROM) enhanced the link between clinical measurements and gait data. The
      variance of gait parameters was better explained by a combined model of static
      and dynamic clinical measurements, compared to a purely static model. However,
      R(2)-values were low. Gait analysis data cannot be sufficiently predicted by a
      combination of clinical measurements. The independence of the measurements
      supports the notion that both, clinical examination and gait analysis data
      provide important information for delineating the problems of children with CP.

PMID- 16303306
TI  - Bifunctional TatA subunits in minimal Tat protein translocases.

PMID- 16303307
TI  - Chemotactic peptides: fMLF-OMe analogues incorporating proline-methionine
      chimeras as N-terminal residue.
AB  - The new fMLF analogues 1-4, incorporating chimeric S-proline-methionine residues
      (namely the homochiral cis-4(S)-methylthio-(S)-proline (10) and the heterochiral
      trans-4(R)-methylthio-(S)-proline) (17) in place of the native S-methionine, have
      been prepared; their solution conformation and activity as agonists or
      antagonists of formylpeptide receptors have been studied. In addition to peptides
      1-4, which maintain the Met gamma-thiomethyl-ether function, the analogues Boc
      PLF-OMe (18) and For-PLF-OMe (19) devoid, as compared with 1-4, of position 1
      side chain, have been synthesized and their activity examined.

PMID- 16303308
TI  - Time-dependent inhibitors of trypanothione reductase: analogues of the spermidine
      alkaloid lunarine and related natural products.
AB  - The macrocyclic spermidine alkaloid lunarine 1 from Lunaria biennis is a
      competitive, time-dependent inhibitor of the protozoan oxidoreductase
      trypanothione reductase (TryR), a promising target in drug design against
      tropical parasitic diseases. Various molecules related to 1 and the alkaloid
      itself have been synthesized in racemic form and evaluated against TryR in order
      to determine the key features of 1 that are associated with time-dependent
      inhibition. Kinetic data are consistent with an inactivation mechanism involving
      a conjugate addition of an active site cysteine residue onto the C-24-C-25 double
      bond of the tricyclic nucleus of 1. Comparison of data for synthetic (+/-)-1, the
      natural product, and other derivatives 7-10 from L. biennis confirms the
      importance of the unique structure of the tricyclic core as a motif for inhibitor
      design and reveals that the non-natural enantiomer may be a more suitable
      scaffold upon which thiophilic groups may be presented.

PMID- 16303309
TI  - Bicyclic and tricyclic thiophenes as protein tyrosine phosphatase 1B inhibitors.
AB  - A novel pyridothiophene inhibitor of PTP1B was discovered by rational screening
      of phosphotyrosine mimics at high micromolar concentrations. The potency of this
      lead compound has been improved significantly by medicinal chemistry guided by X
      ray crystallography and molecular modeling. Excellent consistency has been
      observed between structure-activity relationships and structural information from
      PTP1B-inhibitor complexes.

PMID- 16303310
TI  - Effect of cholesterol on DMPC phospholipid membranes and QSAR model construction
      in membrane-interaction QSAR study through molecular dynamics simulation.
AB  - In this study, both pure DMPC and DMPC/cholesterol mixed membrane monolayer were
      built to compare the physical-chemical properties and dynamics properties through
      molecular dynamics simulation and normal-mode analysis. The results show that the
      addition of cholesterol decreases the area of per molecule of membrane, increases
      the lipid amplitude motion, and changes the solute diffusion coefficient. It is
      also found that the addition of cholesterol greatly changes the solute-membrane
      1,4-nonbonded interaction energy (deltaE14). MI-QSAR models were constructed
      based on solute-membrane interaction energy descriptors and other intramolecular
      descriptors. The results show that deltaE14 substitutes deltaE(HB) as the second
      important descriptor compared with the previous study. Final results suggest that
      short range solute-membrane interaction energy changes due to the uptake of the
      solute may play an important decision on permeability in DMPC/cholesterol
      membrane. A test set was applied to evaluate the predictivity of MI-QSAR models.
      The result suggests that the combination of F(H2O) and deltaE14 not only improves
      r2 and q2, but also greatly improves the model predictivity. Based on the
      combination of q2 and r(pre)2 values, a two-term model is better used to predict
      the solute permeability in this study (r2 = 0.859, q2 = 0.803, and r(pre)2 =
      0.540). Due to the small sample both in training set and test set, more datasets
      are necessary to make a final decision about the model construction and
      prediction.

PMID- 16303311
TI  - Design, synthesis, and SAR analysis of cytotoxic sinapyl alcohol derivatives.
AB  - Five series totalling 51 of sinapyl alcohol derivatives were designed and
      synthesized. Their cytotoxicity analyses were performed on six human tumor cell
      lines such as PC-3, CNE, KB, A549, BEL-7404, and HeLa. Certain sinapyl alcohol
      derivatives showed significant cytotoxic activities. Compound 14d exhibited
      especially potent cytotoxicity against the BEL-7404 cell line with an IC50 value
      of 0.7 microM, which showed more cytotoxic activity than the positive control,
      cisplatin. The structure-cytotoxicity relationships were discussed and the CoMFA
      analysis was performed using the cytotoxic data against HeLa cells as a template.

PMID- 16303312
TI  - Some results of a simulated test for administration of activity in nuclear
      medicine.
AB  - This paper describes the results obtained using a simulated test for
      administration of activity in nuclear medicine between 2002 and 2004.
      Measurements in the radionuclide calibrator are made during the different stages
      of the procedure. The test attempts to obtain supplementary information on the
      quality of the measurement, with the aim of evaluating in a more complete way the
      accuracy of the administered activity value compared with the prescribed one. The
      participants' performance has been assessed by means of a statistical analysis of
      the reported data. Dependences between several attributes of the simulated
      administration tests results are discussed. Specifically, the proportion of
      satisfactory results in the 2003-2004 period was found to be higher than in 2002.
      It reveals an improvement of the activity administration in the Cuban nuclear
      medicine departments since 2003.

PMID- 16303313
TI  - Macrophage-colony stimulating factor enhances MHC-restricted presentation of
      exogenous antigen in dendritic cells.
AB  - Previous studies have shown that dendritic cells (DCs) can phagocytize, process
      and present a microencapsulated form of ovalbumin (OVA) in the context of class I
      MHC as well as class II MHC. In the present study, we examined the effects of
      recombinant human macrophage-colony stimulating factor (M-CSF) on the MHC
      restricted presentation of microencapsulated OVA by DCs. Two types of DCs were
      generated from mouse bone marrow (BM) cells, one type with granulocyte/macrophage
      colony stimulating factor (GM-CSF) alone, the other type with GM-CSF and
      interleukin (IL)-4. Pretreatment with M-CSF significantly enhanced both class I
      MHC and class II MHC-restricted presentation of exogenous OVA by both types of
      DCs. The enhancing activity of M-CSF on antigen presentation was more potent in
      DCs generated with GM-CSF alone compared to DCs generated with both GM-CSF and IL
      4. Pretreatment of the DCs with M-CSF did not increase phagocytic activity or
      total level of expression of class I MHC (H-2K(b)) molecules, but increased
      expression of OVA peptide-H-2K(b) complexes upon phagocytosis of
      microencapsulated OVA. These results demonstrate that M-CSF increases
      intracellular processing events of phagocytized antigen in DCs.

PMID- 16303314
TI  - IL-7: a key regulator of B lymphopoiesis.
AB  - Interleukin-7 plays important roles in the B cell developmental pathway including
      events leading to commitment, survival, proliferation, and maturation. Because of
      its central role in adult murine B lymphopoiesis, IL-7 is frequently used to
      generate B cell progenitors in vitro. We have shown that differentiation of IL-7
      responsive cells in these cultures is influenced by CD45, pre-B cell receptor,
      and other downstream signaling molecules. A common, but often overlooked aspect
      of IL-7 containing cultures is the routine maturation of cells to the sIgM(+)
      stage. The production of B cells in IL-7 containing cultures is balanced by cell
      death, since such cells fail to survive for long without additional stimulation.

PMID- 16303315
TI  - Random-effects models in investigating the effect of vitamin A in childhood
      diarrhea.
AB  - PURPOSE: By adopting more appropriate and powerful statistical methods that fully
      exploit longitudinal structure, we re-analyze and extend previously published
      results from a large community trial to investigate the effect of vitamin A
      supplementation on the prevalence and severity of diarrhea in young children.
      METHODS: Generalized linear mixed models were used to allow for repeated measures
      in a reanalysis of a double-blind, randomized, placebo-controlled community trial
      conducted in a cohort of children in northeastern Brazil during 1 year. The
      response variable was weekly number of days with diarrhea for each child, and
      Markov Chain Monte Carlo methods were used to estimate model parameters. RESULTS
      AND CONCLUSIONS: Random effects suitably accounted for the underlying
      heterogeneity between and within children, and our longitudinal analysis shows a
      significant beneficial effect of vitamin A supplementation that was inconclusive
      in previously reported simple summary analyses of these data. Risk for diarrhea
      infection was estimated to be 1.57 times greater for a child administered a
      placebo as opposed to vitamin A (95% credible interval, 1.17-2.12). Additionally,
      we identified previously unreported temporal effects in these data, showing a
      decreasing daily probability of diarrhea for both groups during the trial and
      treatment-time interaction.

PMID- 16303316
TI  - Fully-automated detection of cerebral water content changes: study of age- and
      gender-related H2O patterns with quantitative MRI.
AB  - We present a simple and robust method for the automated image analysis of
      quantitative cerebral water content maps acquired with MRI. The method is based
      on a new approach for the absolute and quantitative mapping of water content in
      vivo. Water content maps were automatically segmented into grey and white matter
      by employing the quantitative T1 information acquired as part of the water
      content mapping procedure. Based on the segmented maps, twenty-two parameters
      sensitive to both absolute water content and its spatial organisation are
      automatically extracted without user interaction. The parameters include, amongst
      others, absolute water content in grey and white matter and spatial asymmetries
      of the cerebral water content distribution. Significant age- and gender-related
      changes in the parameters determined were observed in a study of forty-four
      healthy subjects. Most notably, the grey matter water content decreases at a rate
      of 0.034%/year for females between the 3rd and 8th decade of life, whilst a much
      stronger decrease is observed in males which sets in after the 5th decade of
      life. In addition, female grey matter water content is, on average, 1.2% higher
      than the respective male grey matter water content. In contrast to the
      heterogeneity observed in grey matter, no significant physiological variation was
      observed for white matter water content. In addition to absolute grey matter
      water content, characteristic age- and gender-specific variations were also
      observed in most of the other variables. To check the potential loss of
      information associated with the large reduction of the dimensionality of the
      dataset to 22 parameters only, the age and gender of each individual subject were
      predicted by employing robust linear discriminant analysis based on only the
      determined twenty-two variables. The median deviation between predicted and real
      age was 6.3 years resulting in a high correlation coefficient between both values
      (r = 0.69). Gender is correctly predicted in 68.2% of all cases which improves to
      87.5% when age-dependent effects are first corrected, demonstrating the high
      information content present in the variables even though the dimension of the
      dataset was significantly reduced. These results form the baseline for future
      studies of cerebral pathology. The method presented is fully automated, robust
      and flexible, making it an ideal tool for routine application in both
      neuroscientific studies and clinical diagnosis based on the quantitative
      measurement of cerebral water content.

PMID- 16303318
TI  - Understanding metamemory: neural correlates of the cognitive process and
      subjective level of confidence in recognition memory.
AB  - An essential feature of human memory is the capacity to assess confidence in
      one's own memory performance, but the neural mechanisms underlying the process of
      determining confidence in memory performance have not yet been isolated. Using
      functional magnetic resonance imaging, we examined both the process of confidence
      assessment and the subjective level of high or low confidence expressed during
      this process. The comparison of confidence assessment to recognition showed
      greater relative activation during confidence assessment in medial and lateral
      parietal regions, which typically deactivate during cognitive tasks, previously
      described as part of the "default network". Furthermore, comparisons of high
      versus low confidence judgments revealed modulation of neural activity in the
      hippocampus, cingulate and other limbic regions, previously described as the
      Circuit of Papez. Our findings suggest that activity in two distinct networks of
      brain regions contribute to the subjective experience of "knowing you know"
      through memory monitoring processes and signaling subjective confidence level for
      recognition memory.

PMID- 16303317
TI  - A temporal comparison of BOLD, ASL, and NIRS hemodynamic responses to motor
      stimuli in adult humans.
AB  - In this study, we have preformed simultaneous near-infrared spectroscopy (NIRS)
      along with BOLD (blood oxygen level dependent) and ASL (arterial spin labeling)
      based fMRI during an event-related motor activity in human subjects in order to
      compare the temporal dynamics of the hemodynamic responses recorded in each
      method. These measurements have allowed us to examine the validity of the
      biophysical models underlying each modality and, as a result, gain greater
      insight into the hemodynamic responses to neuronal activation. Although prior
      studies have examined the relationships between these two methodologies through
      similar experiments, they have produced conflicting results in the literature for
      a variety of reasons. Here, by employing a short-duration, event-related motor
      task, we have been able to emphasize the subtle temporal differences between the
      hemodynamic parameters with a high contrast-to-noise ratio. As a result of this
      improved experimental design, we are able to report that the fMRI measured BOLD
      response is more correlated with the NIRS measure of deoxy-hemoglobin (R = 0.98;
      P < 10(-20)) than with oxy-hemoglobin (R = 0.71), or total hemoglobin (R = 0.53).
      This result was predicted from the theoretical grounds of the BOLD response and
      is in agreement with several previous works [Toronov, V.A.W., Choi, J.H., Wolf,
      M., Michalos, A., Gratton, E., Hueber, D., 2001. "Investigation of human brain
      hemodynamics by simultaneous near-infrared spectroscopy and functional magnetic
      resonance imaging." Med. Phys. 28 (4) 521-527.; MacIntosh, B.J., Klassen, L.M.,
      Menon, R.S., 2003. "Transient hemodynamics during a breath hold challenge in a
      two part functional imaging study with simultaneous near-infrared spectroscopy in
      adult humans". NeuroImage 20 1246-1252.; Toronov, V.A.W., Walker, S., Gupta, R.,
      Choi, J.H., Gratton, E., Hueber, D., Webb, A., 2003. "The roles of changes in
      deoxyhemoglobin concentration and regional cerebral blood volume in the fMRI BOLD
      signal" Neuroimage 19 (4) 1521-1531]. These data have also allowed us to examine
      more detailed measurement models of the fMRI signal and comment on the roles of
      the oxygen saturation and blood volume contributions to the BOLD response. In
      addition, we found high correlation between the NIRS measured total hemoglobin
      and ASL measured cerebral blood flow (R = 0.91; P < 10(-10)) and oxy-hemoglobin
      with flow (R = 0.83; P < 10(-05)) as predicted by the biophysical models.
      Finally, we note a significant amount of cross-modality, correlated, inter
      subject variability in amplitude change and time-to-peak of the hemodynamic
      response. The observed co-variance in these parameters between subjects is in
      agreement with hemodynamic models and provides further support that fMRI and NIRS
      have similar vascular sensitivity.

PMID- 16303319
TI  - Adaptive pacing of visual stimulation for fMRI studies involving overt speech.
AB  - We report the development of an interactive approach to single-word language
      production studies in fMRI. The approach, adaptive pacing, involves real-time
      adjustment of stimulus presentation times based on individual subject performance
      timing and content. At the same time, it maintains a stochastic distribution of
      interstimulus intervals to avoid confounding task covariates with speech-related
      signal variance. Adaptive pacing of overt speech production is an example of a
      new class of paradigms that require an observational approach to data acquisition
      and benefit from a "time-aware" acquisition and processing environment. The
      advantages of adaptive pacing in fMRI of impaired subjects are expected to be the
      acquisition of more informative data per unit time, less contamination of data by
      correlates of non-language processes such as emotion, and facilitation of
      experiments that combine normal and impaired subjects.

PMID- 16303320
TI  - Effects of long-term, high-altitude hypoxia on tension and intracellular calcium
      responses in coronary arteries of fetal and adult sheep.
AB  - OBJECTIVES: We have previously shown that after exposure to long-term hypoxia,
      fetal coronary flow is maintained at control levels despite a 25% reduction in
      cardiac output. We also demonstrated that coronary vascular rings isolated from
      the long-term hypoxic fetuses and studied in well-oxygenated bath system
      displayed significantly reduced depolarization-induced contraction strength in
      response to KCl. To study the mechanism of reduced fetal coronary vascular
      responses to KCl-induced contractions following exposure to long-term hypoxia, we
      measured tension and intracellular calcium simultaneously, as well as L-type Ca2+
      channel density and sensitivity. METHODS: Pregnant ewes were housed at altitude
      (3820 m) for approximately 110 days. At 138 to 141 days of gestation, long-term
      hypoxic and control animals were killed and fetal and adult left anterior
      descending coronary artery (LAD) was isolated and studied in a well-oxygenated
      bath system. Tension and intracellular calcium ([Ca2+]i) were measured
      simultaneously in response to increasing concentrations of KCl and, in addition,
      the sensitivity to the calcium channel blocker nifedipine was measured at a half
      maximal concentration of KCl. We also measured L-type Ca2+ channel density with
      (+)-[3H]PN200-110. RESULTS: L-type Ca2+ channel density was decreased by
      approximately 31% in the long-term hypoxic fetal, but not adult, LAD. Tension in
      the long-term hypoxic fetal and adult LAD was significantly lower at all
      concentrations of KCl. [Ca2+]i was lower at rest in both fetal and adult LAD from
      long-term hypoxic animals and increased to lower levels at all concentrations of
      KCl. The ratio of tension to [Ca2+]i was also lower at all concentrations of KCl.
      Sensitivity to nifedipine was unchanged. CONCLUSIONS: The reduced L-type Ca2+
      channel density and the reduced [Ca2+]i response to KCl, as well as the reduced
      tension response to [Ca2+]i, could potentially be involved in the reduction in
      depolarization-induced contractions in LAD from long-term hypoxic fetuses. In
      hypoxic adults, reduced [Ca2+]i and reduced tension response to [Ca2+]i may be
      involved in the lower tension response to KCl-induced contractions.

PMID- 16303321
TI  - Advances in understanding the molecular causes of diabetes-induced birth defects.
AB  - OBJECTIVE: To review the current understanding of the molecular causes of birth
      defects resulting from diabetic pregnancy, with a focus on neural tube defects.
      METHODS: A mouse model of diabetic pregnancy is described, in which embryo gene
      expression associated with neural tube defects is examined. Chemical,
      physiologic, or genetic manipulations are employed to elucidate critical pathways
      affected by increased glucose metabolism, and how abnormal gene expression
      disrupts neural tube closure. RESULTS: Increased glucose delivery to embryos, or
      activation of pathways that are stimulated by high glucose, such as the
      hexosamine biosynthetic pathway or hypoxia, increase oxidative stress in embryos,
      inhibit expression of Pax3, a gene that encodes a transcription factor that is
      required for neural tube closure, and increase neural tube defects. Conversely,
      blocking these pathways, or providing the antioxidants, reduced glutathione or
      vitamin E, suppress the adverse effects of excess glucose. Pax3 decreases steady
      state levels of the p53 tumor-suppressor protein, such that when Pax3 is
      deficient, p53 protein increases, leading to increased neuroepithelial apoptosis
      prior to completion of neural tube closure. Embryos that lack both functional
      Pax3 protein and p53 do not display neuroepithelial apoptosis or neural tube
      defects. CONCLUSIONS: Excess glucose metabolism by embryos resulting from
      maternal hyperglycemia disturbs a complex network of biochemical pathways,
      leading to oxidative stress. Oxidative stress inhibits expression of genes, such
      as Pax3, which control essential developmental processes. Pax3 protein is
      required during neural tube development to suppress p53-dependent cell death and
      consequent abortion of neural tube closure, but is not required to control
      expression of genes that direct neural tube closure. Impaired embryo gene
      expression resulting from oxidative stress, and consequent apoptosis or disturbed
      organogenesis, may be a general mechanism to explain diabetic embryopathy.

PMID- 16303322
TI  - Labor-associated regulation of prostaglandin E and F synthesis and action in the
      ovine amnion and cervix.
AB  - OBJECTIVE: Prostaglandins (PGs) are key regulators of cervical dilatation and
      membrane breakdown at the onset of labor. PG synthase and receptor expression has
      been previously documented in uterine tissues; however, mechanisms governing the
      changes occurring in the cervix and amnion are less well established. The aim of
      the current study was to determine the level of expression of PG synthetic
      enzymes and receptors in these tissues in association with induced labor in
      sheep. METHODS: Labor was induced in sheep at 135 days of gestation by continuous
      fetal dexamethasone infusion. Amnion and cervical tissue was obtained before and
      after labor for measurement of mRNA encoding enzymes (cytosolic phospholipase A2
      [cPLA2], PGH synthase-2 [PGHS-2], PGF synthase [PGFS], and PGE synthase [PGES])
      and receptors (FP and EP1-4) by real-time polymerase chain reaction (PCR).
      RESULTS: cPLA2 expression increased significantly in cervical tissue at labor
      onset, whereas expression of the other enzymes measured did not change. There was
      a marked rise in EP3 expression in the cervix, but abundance of this receptor was
      lower than EP2 and FP expression, which did not change. The amnion exhibited a
      labor-associated decrease in PGHS-2, PGFS, and FP mRNA expression. CONCLUSION:
      The regulation of PG synthesis and action occurring in the amnion and cervix in
      association with labor appear to differ markedly between the two tissues,
      indicating tissue-specific roles for PGs. The data support a role for increased
      PG synthesis and action in the cervix and suggest a decrease in PG production and
      action in the amnion, in sharp contrast to the pattern reported in human amnion.

PMID- 16303323
TI  - An imbalance between vascular endothelial growth factor and its soluble receptor
      in placental villous explants of intrauterine growth-restricted pregnancies.
AB  - OBJECTIVES: Human umbilical vascular endothelial cells (HUVECs), seeded on
      Matrigel (BD Biosciences, Bedford, UK), undergo an angiogenic-like process. We
      hypothesized that placental explants from normal pregnancies, maintained in
      cultures of different oxygen, would liberate factors that could be measured in
      this system. We further tested the angiogenic potential of placentae from
      intrauterine growth-restricted (IUGR) pregnancies and the effects of vascular
      endothelial growth factor (VEGF) blockade. METHODS: Placental villous explants
      were maintained in culture at 3% and 20% O2. The resultant media was added to
      HUVECs seeded on 80% Matrigel. Cells were incubated at 6% O2 in accordance with
      the natural placental environment. After 6 hours, cells were fixed and stained
      and the length and number of tubules measured by morphometric imaging. Finally,
      VEGF and soluble VEGF receptor (sVEGFR-1) were recorded in the explant
      conditioned media. RESULTS: Within the angiogenic assay, recombinant human VEGF
      significantly enhanced tubule outgrowth (branching and elongation) and this
      effect was blocked with neutralising antibody. Compared to 20% O2, media of
      placental explants conditioned at 3% O2 significantly encouraged tubule length
      and numbers. Again this affect was ablated by VEGF blockade. In cases of IUGR,
      conditioned media at 3% O2 showed a significant reduction in tubule growth. This
      was paralleled by a decline in available VEGF brought about an exaggeration in
      liberated sVEGFR-1. Notably, venous cord serum from IUGR pregnancies showed a
      similar elevation in sVEGFR-1. CONCLUSION: Under restricted oxygen, placental
      angiogenic potential is suppressed in IUGR pregnancies through the overproduction
      of placental sVEGFR-1. This reduction may discourage normal placental
      vascularization and impact on fetal development.

PMID- 16303324
TI  - Human cytidine deaminase: a three-dimensional homology model of a tetrameric
      metallo-enzyme inferred from the crystal structure of a distantly related dimeric
      homologue.
AB  - Cytidine deaminase (CDA) is a cytosolic metalloprotein whose functional unit can
      be either a homotetramer (T-CDA) or a homodimer (D-CDA), depending on the
      species. In 1994, the first crystal structure of the dimeric Escherichia coli CDA
      has been published. However, a crystal structure of a tetrameric CDA was not
      determined until 2002. Prior to the disclosure of the experimentally elucidated
      structure of a tetrameric CDA, we derived a homology model of the human T-CDA
      employing the crystal structure of the dimeric E. coli CDA as a template. The
      comparison of our theoretical model with the crystal structure of the human T
      CDA, subsequently published in 2004, validates our prediction: not only of the
      structural features of the monomer and the details of the binding site, but also
      the multimeric arrangement of the subunits were determined with high accuracy in
      our model. By means of a phylogenetic analysis conducted on CDAs from various
      organisms, we demonstrate that the E. coli CDA is one of the furthest known
      homologues of the human enzyme. Nonetheless, despite the evolutionary distance
      and, more importantly, the different multimeric arrangement of their functional
      units, the E. coli CDA proved to have all the necessary information to accurately
      infer the structure of its human homologue.

PMID- 16303325
TI  - Light-emitting conjugated molecule containing 1,3,4-oxadiazole, carbazole and
      naphthalene units.
AB  - A novel pi-conjugated small molecule VNCO, 2,5-bis{3'-[3''-vinyl-9''-(alpha
      naphthyl)carbazolyl]phenyl}-1,3,4-oxadiazole, containing hole-transporting
      carbazole moieties, electron-injecting 1,3,4-oxadiazole moieties and chromophore
      naphthalene was designed and synthesized by Wittig reaction of 2,5-bis(3-tolylene
      triphenylphosphonium bromide)-1,3,4-oxadiazole and 3-formyl-9-(alpha
      naphthyl)carbazole. The UV-vis absorption, fluorescence excitation and emission
      spectra have been obtained in solution for VNCO. The photoluminescence (PL) of
      VNCO were examined in different solvents and the luminescence quantum yield was
      0.746 in chloroform. It emitted blue and blue-green light, with the band gap of
      3.30 eV estimated from the onset absorption. In addition, the light-emitting can
      be quenched by both electron donor (N,N-dimethylaniline) and electron acceptor
      (dimethylterephalate). Furthermore, the molecular interactions of VNCO with
      fullerene (C60) or carbon nanotubes (CNTs) were also carefully investigated.

PMID- 16303326
TI  - Optimal timing of interferon treatment for acute hepatitis C.

PMID- 16303327
TI  - Cis-9,trans-11-CLA exerts anti-inflammatory effects in human bronchial epithelial
      cells and eosinophils: comparison to trans-10,cis-12-CLA and to linoleic acid.
AB  - Interaction of eosinophils and bronchial epithelial cells plays a pivotal role in
      maintaining inflammatory airway disease. Since conjugated linoleic acids (CLA)
      are suggested to exert anti-inflammatory effects, one purpose of this study was
      to compare cis-9,trans-11-CLA and trans-10,cis-12-CLA with regard to their
      influence on the stimulus-induced activation of eosinophils. ECP (eosinophil
      cationic protein) released in co-culture of stimulated and CLA-treated
      eosinophils with stimulated bronchial epithelial cells (BEAS-2B) was measured and
      cis-9,trans-11-CLA was found to be most potent in inhibiting ECP formation.
      Further, expression of the activation markers CD69 and CD13 induced by various
      stimuli (TNF-alpha, IL-5, IL-3) was significantly reduced in the presence of cis
      9,trans-11-CLA. Subsequently, various concentrations of cis-9,trans-11-CLA vs.
      linoleic acid (LA, cis-9,cis-12-octadecadienoic acid) were tested for the effect
      on proliferative response and release of the pro-inflammatory cytokine IL-8 in
      stimulated BEAS-2B. Addition of cis-9,trans-11-CLA attenuated cell growth and
      significantly reduced IL-8 production at mRNA and protein levels. In contrast, LA
      had a slight stimulating effect on proliferation and was less effective in
      reducing the cytokine release. It was demonstrated that the inhibitory effect of
      cis-9,trans-11-CLA on IL-8 production is mediated through activation of the
      nuclear receptor PPARgamma, since blocking the receptor with a selective
      antagonist (GW9662) restored the stimulus-induced enhancement in IL-8 mRNA
      expression and protein secretion. PPARgamma has previously been shown to be
      closely involved in the downregulation of inflammation during hyperresponsiveness
      related to pulmonary immune responses. Thus, targeting PPARgamma, cis-9,trans-11
      CLA might be of therapeutic value in the focus of airway disease while
      ameliorating inflammatory processes by affecting epithelial and eosinophil
      functions.

PMID- 16303328
TI  - Relationship between QRS duration, left ventricular volumes and prevalence of
      nonviability in patients with coronary artery disease and severe left ventricular
      dysfunction.
AB  - BACKGROUND: Patients with coronary artery disease (CAD), a QRS duration >or=120
      ms and left ventricular ejection fraction (LVEF) <or=30% are potential candidates
      for cardiac resynchronization therapy (CRT). Our aim was to investigate the
      relationship between QRS duration, left ventricular volumes and prevalence of
      nonviable tissue in this patient population. METHODS: We studied 132 patients
      (118 men, age 68+/-5 years) with CAD and LVEF <or=30% (mean LVEF 24+/-6%). LV
      volumes and myocardial viability were determined by gated myocardial perfusion
      imaging. RESULTS: A QRS duration >or=120 ms was present in 91 patients (69%).
      Although there were no differences in LVEF, patients with longer QRS durations
      had significant larger end-diastolic and end-systolic volumes (p<0.01).
      Substantial nonviable tissue in the inferior or lateral wall was present in 29%
      of patients with a QRS duration >or=120 ms versus 7% of those with a QRS duration
      <120 ms (p<0.01). CONCLUSIONS: An increased QRS duration is associated with more
      advanced remodeling in patients with CAD and poor LV function. Almost one third
      of these patients with a prolonged QRS duration have no viable tissue in the
      inferolateral wall, an area that is usually stimulated with CRT.

PMID- 16303329
TI  - Cancer-related fatigue in children and young people: survey of healthcare
      professionals' knowledge and attitudes.

PMID- 16303330
TI  - Embedding cancer care within pre-registration nurse education programmes: policy,
      practice and opportunities for change.
AB  - This paper discusses policy and professional drivers which outline the need for,
      and inclusion of cancer education within pre-registration nursing curricula
      within the UK. It also evaluates arguments in favour of the development of
      separate and distinctive cancer modules within nurse training programmes against
      those advocating a more integrated or thematic approach. The authors suggest that
      there are advantages and disadvantages to each strategy, and argue that the most
      important factor irrespective of the approach taken, is that cancer learning
      outcomes are clearly enunciated within all pre-registration nursing curricula and
      constructively aligned against teaching, learning and assessment strategies which
      may encompass a single module or entire programme. The authors then discuss their
      personal experience of teaching cancer care using both approaches and posit one
      suggestion for an embedded pre-registration cancer-care curriculum developed as
      the catalyst for a broader debate on the scope and content of cancer-care
      education within pre-registration nursing curricula.

PMID- 16303331
TI  - Deworming: adding public health education to the equation.

PMID- 16303332
TI  - Giardia immunity--an update.
AB  - Giardia lamblia is a flagellated protozoan that causes watery diarrhea worldwide
      but the mechanisms of pathogenicity and the major host defenses against Giardia
      infection are not well characterized. The recent sequencing of the G. lamblia
      genome and the development of methods for genome-wide analyses of gene expression
      have made it possible to characterize the host-parasite interaction more fully.
      It is becoming clear that the host defense against a Giardia infection involves
      several different immunological and non-immunological mucosal processes.

PMID- 16303333
TI  - Simultaneous aberrations in Mphi and T cell function adversely affect trauma
      patients' clinical outcome: a possible faulty IL-13 feedback loop.
AB  - Possible defective trauma patients' Mphi-T-cell feedback interactions between T
      cell IL-13 production and IL-1beta and IL-18 Mphi secretion were assessed. Mphi
      produced IL-1 and IL-18 augment T cell IL-13, which in turn limits excessive
      macrophage activation. Immunodepressed patients' T cells (depressed proliferation
      to alphaCD3 + alphaCD4) had decreased IL-13 production concomitant to aberrant
      Mphi activities ( upward arrow mTNFalpha, downward arrow IL-10) and consequent
      multiple organ failure (MOF). Decreased IL-13 levels in patients' T cell and
      diminished Mphi supernatant augmentation of healthy controls' T cell IL-13
      production appeared concomitantly, suggesting patients' aberrant monokine levels
      might intensify in vivo T cell dysfunction severity. Patients' Mphi supernatants,
      which failed to augment controls' T cell IL-13 production, had depressed IL-1beta
      and lower induction of IL-18 than immunocompetent patients' Mphi, but combined
      addition of IL-1beta and IL-18 restored these Mphis' IL-13 enhancing activity.
      These data suggest that immunodepressed patients' aberrant monokine and depressed
      T cell IL-13 production are independent but synergistic contributors to emergence
      of MOF.

PMID- 16303334
TI  - Inflammatory modulation of PPAR gamma expression and activity.
AB  - Nitric oxide (NO) production increases with age in the lupus-prone MRL/lpr mouse,
      paralleling disease activity. One mechanism for excess NO production in MRL/lpr
      mice may be a defect in down-regulatory mechanisms of the iNOS pathway. A
      potential modulator of NO is the nuclear hormone receptor peroxisome
      proliferation activated receptor gamma (PPARgamma). We demonstrate that renal
      PPARgamma protein expression was altered as disease progressed in MRL/lpr mice,
      which paralleled increased iNOS protein expression. Additionally, MRL/lpr-derived
      primary mesangial cells expressed less PPARgamma than BALB/c mesangial cells and
      produced more NO in response to LPS and IFNgamma. Furthermore, PPARgamma activity
      was reduced in mesangial cells following exposure to inflammatory mediators. This
      activity was restored with the addition of a NOS enzyme inhibitor. These results
      indicate that the activation of inflammatory pathways may lead to reduced
      activity and expression of PPARgamma, further exacerbating the disease state.

PMID- 16303335
TI  - Dynamic LV obstruction in apical ballooning syndrome: the chicken or the egg.

PMID- 16303336
TI  - A haplotype of angiotensinogen gene that is associated with essential
      hypertension increases its promoter activity in adipocytes.
AB  - Obesity is associated with hypertension and other cardiovascular diseases
      especially in the African-American population. Human angiotensinogen (AGT) gene
      has seven single nucleotide polymorphisms (SNPs) in 1.2 kb region of its
      promoter. Recent studies have shown that variant -217A is associated with
      hypertension in African-American and Chinese population. Nucleotide sequence of
      the hAGT gene has shown that variant -217A almost always occurs with variants 
      532T, -793A and -1074T (forming haplotype AAT) and variant -217G almost always
      occurs with variants -532C, -793G and -1074G (forming haplotype GGG). Since hAGT
      gene is expressed in the adipose tissue and its expression in this tissue may
      play a role in hypertension, we have analyzed the role of haplotypes AAT and GGG
      on the expression of this gene in adipocytes. We show here that a reporter
      construct with haplotype AAT of the hAGT gene has increased promoter activity on
      transient transfection in pre-adipocytes and differentiated adipocytes as
      compared to the reporter construct containing GCGG haplotype. Increased
      expression of the AGT gene containing haplotype AAT in the liver and adipocytes
      may be a contributing factor for hypertension.

PMID- 16303337
TI  - Chaotic dynamics of resting ventilatory flow in humans assessed through noise
      titration.
AB  - The mammalian ventilatory behaviour exhibits nonlinear dynamics as reflected by
      certain nonlinearity or complexity indicators (e.g. correlation dimension,
      approximate entropy, Lyapunov exponents, etc.) but this is not sufficient to
      determine its possible chaotic nature. To address this, we applied the noise
      titration technique, previously shown to discern and quantify chaos in short and
      noisy time series, to ventilatory flow recordings obtained in quietly breathing
      normal humans. Nine subjects (8 men and 1 woman, 24-42 years) were studied during
      15-min epochs of ventilatory steady-state (10.1+/-3.0 breaths/min, tidal volume
      0.63+/-0.2 L). Noise titration applied to the unfiltered signals subsampled at 5
      Hz detected nonlinearity in all cases (noise limit 20.2+/-12.5%). Noise limit
      values were weakly correlated to the correlation dimension and the largest
      Lyapunov exponent of the signals. This study shows that the noise titration
      approach evidences a chaotic dimension to the behavior of ventilatory flow over
      time in normal humans during tidal breathing.

PMID- 16303338
TI  - Crystallisation and preliminary structure determination of a NADH: quinone
      oxidoreductase from the extremophile Acidianus ambivalens.
AB  - NADH:quinone oxidoreductases (NDHs), constitute one of the electron entry points
      into membrane-bound respiratory chains, oxidising NADH and reducing quinones.
      Type-II NDHs (NDH-2) are functionally unable to translocate protons and are
      typically constituted by a single approximately 50 kDa subunit lacking iron
      sulfur clusters and containing one flavin as the sole redox centre. No three
      dimensional crystal structure is yet available for NDHs. We describe the
      crystallisation and preliminary structure determination of a NDH-2 that contains
      a covalently bound FAD, isolated from the membrane fraction of Acidianus
      ambivalens, a hyperthermoacidophilic archaeon capable of growing at 80 degrees C
      and pH 2.0. NDH-2 was solubilised with the detergent n-dodecyl-beta-d-maltoside
      and crystallised using ammonium phosphate as precipitant. The structure was
      solved by MIRAS using Pt and I derivatives.

PMID- 16303340
TI  - Editorial.

PMID- 16303339
TI  - The study of solution conformation of allatostatins by 2-D NMR and molecular
      modeling.
AB  - More than 70 allatostatins have been isolated from various insects and there is
      interest in the determination of their active conformation. We have synthesized
      Dippu-AST 1 (originally isolated from the cockroach Blattella germanica) and
      studied its conformation in solution by 2-D NMR and molecular modeling. Dippu-AST
      1 belongs to the cockroach-type ASTs that have Y/FXFGL-NH(2) as the common C
      terminal sequence. We found that Dippu-AST 1 forms a type I' beta-turn
      conformation in DMSO. We also studied the conformations of Dippu-AST 1 and six
      cockroach-type allatostatins in water using the molecular dynamics method. When
      the X amino acid in the consensus sequence Y/FXFGL-NH(2) is Ala or Ser, the
      allatostatin can form a typical type II beta-turn. If the X is Asp or Asn whose
      side chain contains a carbonyl, the allatostatin can form a type I, I' or IV beta
      turn conformation; if the X is Gly, a closer gamma-turn is adopted. Our study
      indicates that the turn conformation is ubiquitous in cockroach-type
      allatostatins.

PMID- 16303341
TI  - Effect of material ionicity on the performance of daily disposable contact
      lenses.
AB  - The surface of hydrophilic contact lenses is intrinsically hydrophobic.
      Biocompatibility requires the contact lens surface to be coated with a
      lipoproteinic biofilm produced by the ocular secretion. For daily disposable
      modality of wear it is essential that biocompatibility, clinically represented by
      good in vivo wettability and subjective acceptance, is achieved as quickly as
      possible following insertion, as the process needs to be repeated daily. It has
      been hypothesised that non-ionic materials will not achieve biocompatibility as
      rapidly as ionic materials owing to the latter's ability to attract high levels
      of adsorbed proteins. The current investigation was a double-masked crossover
      study that evaluated, over 1 week of wear, a new non-ionic material (Nelfilcon A)
      and a current ionic material (Etafilcon A) under daily disposable modality. The
      results obtained showed that overall, both contact lens materials achieved good
      in vivo tear stability over the first 30 min of wear and good subjective
      acceptance that remained stable over the period of wear. The results obtained
      demonstrate that a non-ionic material can achieve rapid biocompatibility and
      subjective acceptance in a similar manner to an ionic material.

PMID- 16303342
TI  - Therapeutic contact lenses and eyedrops--is there a problem?
AB  - Numerous authors have investigated the interactions of contact lenses with their
      care solutions. Many reported hypersensitivity and toxicity reactions induced by
      the preservative in the care solution, especially with soft contact lenses. In
      medical contact lens practice the concurrent use of eyedrops in a patient wearing
      therapeutic contact lenses is a contentious issue. The usual practice is to
      prescribe unpreserved drops. In reviewing the literature, we found no evidence of
      complications using preserved eyedrops with such contact lenses in situ. The
      reluctance to prescribe preserved topical medication could stem from the evidence
      relating to contact lens care solutions.

PMID- 16303343
TI  - Comparative performance of disposable soft contact lenses.
AB  - A short-term clinical study was undertaken to compare and evaluate the fit and
      clinical behaviour of eight disposable hydrogel contact lenses. Thirty subjects
      were enrolled in a 1-day, randomised, double-masked study. The lenses compared
      were Vistakon Acuvue (8.80), Vistakon Surevue (8.80), Aspect Frequency-55, Bausch
      & Lomb Medalist (SeeQuence 2), Ciba Focus (8.90), Lunelle Rythmic, Pilkington
      Barnes Hind Precision-Wand Wesley Jessen Freshlook. Three of the eight designs,
      Acuvue (86.7%), Precision-UV (86.7%) and Frequency-55 (90%), achieved relatively
      high levels of fitting success. The Rythmic lenses achieved the lowest success
      rate (70%) showing significantly greater downward decentration than the other
      designs. Although all the lenses were designed to fit a wide variety of eyes,
      they exhibited widely varying fitting characteristics. Some were more successful
      than others. The study shows that it is necessary for practitioners to utilise a
      range of lens designs in order to fit satisfactorily the typical contact lens
      population.

PMID- 16303344
TI  - Clinical comparison of three polyhexanide-preserved multi-purpose contact lens
      solutions.
AB  - This study investigated the clinical differences between three commercially
      available polyhexanide (PHMB) preserved disinfection systems containing varying
      percentages of PHMB, when used with FDA group II and group IV disposable contact
      lenses. After 1 month of wear the product with the highest concentration of PHMB
      ('All-in-One') was graded as being less comfortable on insertion (P<0.003), had
      lower overall satisfaction (P<0.05) when compared with the other two products.
      Corneal staining was also significantly higher with this product after both 14
      days (P<0.001 with group II and P<0.02 with group IV) and 28 days (P<0.00001 with
      group II and P<0.03 ith group IV).

PMID- 16303345
TI  - Editorial.

PMID- 16303346
TI  - Analysis of the colleting method of producing spherical surfaces in contact lens
      blanks using finite element and experimental methods.
AB  - In contact lens manufacturing, the collet chuck is one of the most common methods
      of holding a lens blank in a lathe in order to cut a back optic zone. In this
      method the lens blank is compressed by a colleting force, and the effects of this
      force on the back optic zone radius of the lens blank are not well known. If
      these effects are known, improved back optic zone radius dimensions may be
      obtained. In this paper, the finite element and experimental results obtained for
      the effects of colleting on the back optic zone radius are presented and
      discussed.

PMID- 16303347
TI  - Analysis of the crimping method of producing toric surfaces in contact lens
      blanks using finite element and experimental methods.
AB  - One of the most common methods of producing a toric surface in a contact lens
      blank is crimping. This method has the advantages of being simple and cheap, but
      the toric surface dimensions obtained, especially at higher cylinders, can be
      less accurate. The relationships between the crimping parameters used to produce
      the toric surface and the dimensions of the toric surface obtained are not well
      known. If these relationships are known, improved toric surface dimensions may be
      obtained. In this paper, finite element analysis and experimental results
      obtained for these relationships are presented and discussed.

PMID- 16303348
TI  - Contact lenses: do they really change the optical performance?
AB  - In this investigation the quality of two types of optical correction, hydrogel
      contact lenses and ophthalmic lenses, was compared by measuring the modulation
      transfer function (MTF) of the correcting lens plus visual optics system using an
      objective method. A merit function was defined in order to allow the direct
      comparison between the optical performance with the two corrections. A study on
      10 subjects was undertaken, measuring the MTF of both corrections by using the
      double pass method. The results show that the optical quality of contact lenses
      was higher than that with ophthalmic lenses. The contrast sensitivity function
      (CSF) and visual acuity (VA) were determined as subjective parameters of visual
      performance.

PMID- 16303349
TI  - Cleaning efficacy of single-purpose surfactant cleaners and multi-purpose
      solutions.
AB  - The initial stages of contact lens spoilation are rapid with respect to the
      deposition of tear components, in particular, lipids and proteins. In addition,
      extrinsic factors such as care solutions, cosmetics, skin lipids, drugs and
      tobacco smoke may all play an important part in the spoilation process. Care
      systems have different effects on this spoilation. Assessment of the relative
      cleaning efficacies of the single purpose and multipurpose cleaners which are now
      available in the UK (e.g. ReNu, Optifree, Complete), is of importance in
      understanding progressive contact lens-tear interactions. This paper furthers our
      understanding of the efficacies of these solutions in removing the deposition of
      tear components from the contact lens.

PMID- 16303351
TI  - Editorial.

PMID- 16303350
TI  - Use of a 'contract' in the management of the child contact lens patient.

PMID- 16303352
TI  - The truth about compliance.
AB  - When confronted with an adverse response to contact lens wear, practitioners are
      often quick to 'blame the victim'. Although patient compliance may well be
      lacking, the reasons for this need to be considered carefully, along with all of
      the other possible contributing factors, if the safety of contact lens wear is to
      be improved. This Presidential Address briefly reviews what the contact lens
      literature has revealed about patient compliance in the context of what has been
      known for many years in general eye care and, indeed, general medicine.
      Essentially, compliance with contact lens systems is poor (40-90% of patients are
      noncompliant) and difficult to predict in individual patients. Neither a
      compliance-enhancement strategy (intense education) nor reduction of the cost of
      goods has any significant effect upon the level of compliance. Assessment of
      personality is not a reliable compliance predictor. A compliance enhancement
      model is proposed which encompasses the following four components: (a) the clinic
      and the practitioner, (b) the patient, (c) the advice that is given, and (d) the
      contact lens industry.

PMID- 16303353
TI  - Post radial keratotomy RGP fitting--a case study.
AB  - The procedure of radial keratotomy produces an abnormal corneal topography, with
      the central cornea being flatter than the periphery. As a result, fitting the
      post-radial keratotomy (RK) patient with rigid gas permeable (RGP) lenses can be
      an enormously difficult task. Unlike standard lens designs, the Ortho-K series of
      lenses, originally designed for use in orthokeratology, possess a back peripheral
      radius (BPR) which is steeper than the back optic zone radius (BOZR). It is
      proposed that these lenses may provide a more acceptable fit than conventional
      RGPs for the post-RK patient.

PMID- 16303354
TI  - Comparative study of pH for different saline and multi-purpose contact lens
      solutions.
AB  - In this study, we determined the pH of different saline and multipurpose contact
      lens solutions available on the Spanish market. We examined 10 samples of 14
      solutions, seven of which are saline solutions and seven multipurpose ones, from
      different manufacturers. Both types of solution were found to have significant
      variations in pH, with values ranging from 6.70 to 7.57 for the saline solutions
      and 6.84 to 7.63 for the multipurpose solutions. We concluded that the solutions
      should not affect the ocular physiological performance because their pH values
      are within the buffering capacity of the eye.

PMID- 16303356
TI  - Editorial.

PMID- 16303355
TI  - Ocular spherical aberration and theoretical through-focus modulation transfer
      functions calculated for eyes fitted with two types of varifocal presbyopic
      contact lens.
AB  - Through focus modulation transfer functions (MTFs) are compared for six different
      cases: an aberration free eye, an eye suffering from typical amounts of
      undercorrected spherical aberration, and each of such eyes wearing either a
      Hydrocurve II or PS45 varifocal contact lens. It is assumed that the measured
      power profiles of the varifocal lenses, which are typical of centre distance and
      centre-near designs, can be approximated to primary spherical aberration, that
      the lenses are well centred, and that the spherical aberrations of each lens and
      eye are additive. It is found that in general, with a 4 mm pupil, reasonable
      modulation transfer is maintained over a greater focal range (by about 1 dioptre)
      with the varifocal-wearing eyes. This implies that useful vision will be given
      over a greater range of object distances, as required by the presbyope. However,
      the maximal modulation transfer with a varifocal is degraded compared with that
      of the eye alone. Since the amount and sign of ocular spherical aberration may
      vary with the individual, it would be expected that any particular design of
      varifocal would be more successful with some wearers than with others.

PMID- 16303357
TI  - The inside story: why contact lens cases become contaminated.
AB  - Contact lens case contamination has become an enigma, both because its role in
      the pathogenesis of lens-related keratitis has remained uncertain, and because
      current contact lens disinfection systems have been ineffective in eliminating
      it. This lecture reviews the evidence regarding the role of lens case
      contamination in the pathogenesis of keratitis and examines the reasons for the
      failure of disinfection systems to minimise lens case contamination.

PMID- 16303358
TI  - Ten years of disposable contact lenses--a review of benefits and risks.
AB  - The performance and benefits as well as the risks and complications of disposable
      soft lenses (single use disposable or re-used 2-4 weeks) are reviewed in relation
      to corneal physiology. Modern designs and advanced technology have resulted in
      disposable lenses providing excellent visual performance. Fewer subjective
      symptoms (e.g. dryness and grittiness), slit-lamp findings (such as injection and
      tarsal abnormalities), and inflammatory responses (papillary conjunctivitis;
      contact lens-induced acute red eye) have been reported with disposable lenses
      than with conventional soft lenses. The risk of contact lens-induced keratitis
      (CLIK) has been reported to be higher for daily wear of disposable lenses than
      for other lens types by UK investigators. Other studies have shown the risk of
      CLIK with disposable lenses to be equal to that with conventional soft lenses,
      and in two extensive Swedish studies, the incidence of severe keratitis was found
      to be significantly lower for daily wear (DW) of disposable lenses than for DW of
      conventional soft and rigid gas permeable lenses. Both the total complication
      rate and the number of unscheduled visits are found to be significantly lower for
      disposable lenses than for conventional soft lenses in several studies. Comfort
      has been reported to be significantly better and overall satisfaction
      significantly greater with disposable lenses than with conventional soft lenses
      according to many studies. These may be important reasons why the success rate
      for disposable lens wear is reported to be fairly high, generally 70-90%. The
      importance of appropriate care for 're-usable disposable lenses' must be
      stressed. One day disposable lenses, if used as directed, will eliminate the risk
      factors of inadequate cleaning and disinfection as well as contaminated lens
      cases.

PMID- 16303359
TI  - Influence of the tear film on optical quality of the eye.
AB  - The optical quality of the tear film of the eye was tested by measuring the
      retinal image before and after the break-up time (BUT). An objective method was
      used based on the evaluation of the retinal image of a point test projected onto
      the fovea. The loss of an entire tear film would result in a decrease in the
      optical quality because of corneal irregularities and the formation of an
      irregular tear lens after the BUT. Our results confirm the expected loss both of
      non-contact lens wearers and contact lens wearers. Also, the fact that the
      optical deterioration found after the BUT is greater for contact lens wearers
      confirms that soft contact lens wear produces a disruption of the tears.

PMID- 16303360
TI  - Clinical evaluation of infrared autorefractors for use in contact lens over
      refraction.
AB  - We examined the ability of autorefractors to provide an accurate means of contact
      lens over-refraction measurement. Over-refraction measures, performed using six
      commercially available automated infrared autorefractors and retinoscopy, were
      compared with subjective refraction. A total of 40 contact lens wearers (20 soft
      lens wearers and 20 rigid gas permeable (RGP) lens wearers) participated in the
      study. All six autorefractors were able to provide over-refraction measures in
      all subjects. Data analysis revealed differences in autorefractor performance
      between the two types of contact lens wearer with greater accuracy and lower
      variability being found in the soft lens wearing subjects compared with the RGP
      group. The level of agreement between retinoscopy and subjective over-refraction
      results was lower in soft lens wear and higher in RGP wear than the levels found
      between the autorefractor and subjective over-refraction measures. We conclude
      that autorefractors provide a useful means of measuring contact lens over
      refraction in soft lens wearers. Over-refraction results should be treated more
      cautiously in RGP wearers.

PMID- 16303361
TI  - Variation in optic zone radii of a contact lens during manufacturing and the
      effects of temperature on this variation.
AB  - There is little information in the literature on the causes of variation in the
      optic zone radii of a contact lens and the effects of temperature on this
      variation. In this study, the lathe cutting method of producing contact lenses
      was reviewed. The cause of the variation in the back optic zone radius was then
      identified as change in the operating condition from that of the calibrating one.
      Also, using finite element and theoretical methods, it was found that the effect
      of an increase in lens blank temperature is to make the back optic zone radius
      obtained steeper than that required, and this effect was verified experimentally.

PMID- 16303363
TI  - Contemporary contact lens care products.
AB  - In recent years there have been significant changes in legislation relating to
      contact lens solutions and during this period many new products have been
      introduced for the effective care of both soft and rigid contact lenses. This
      paper reviews these various developments and emphasises the importance of
      providing appropriate education for the patient without which the various systems
      cannot be used either safely or efficiently.

PMID- 16303364
TI  - The silicone rubber contact lens: clinical indications and fitting technique.
AB  - Although the silicone rubber contact lens (SRCL) is not used frequently, there
      area number of clinical indications for its use which include paediatric and
      adult aphakia, decompensated cornea, dry eye, irregular cornea, eyelid defects,
      corneal ulcer and corneal perforation. The properties of silicone rubber are
      reviewed and the fitting technique of the SRCL is described.

PMID- 16303365
TI  - A survey of contact lens wear among diabetic patients in the United Kingdom.
AB  - A survey of attitudes to the fitting of contact lenses to diabetic patients was
      sent to 1122 optometric, ophthalmological and dispensing members of the British
      Contact Lens Association; 418 completed questionnaires were analysed. Sixty-two
      per cent of practitioners considered rigid lenses to be the safest form of lens
      wear. Most preferred daily lens wear and advised frequent aftercare visits,
      regular soft lens replacement, special attention to hygiene and restricted
      wearing time. A survey of 218 diabetic patients attending three diabetic clinics
      revealed that 3% wore contact lenses, which is a similar percentage to the non
      diabetic population. Eight patients had been advised that they could not wear
      contact lenses because of their diabetes. It is concluded that controlled
      clinical trials of contact lens wear by diabetic patients are required to
      supplant anecdotal opinions (such as those reported here) with sound scientific
      data in order to form a proper rationale for the safe fitting of contact lenses
      to this group of patients.

PMID- 16303366
TI  - Editorial.

PMID- 16303368
TI  - Editorial.

PMID- 16303367
TI  - Contact lenses and the red eye.
AB  - Patients wearing contact lenses may present with a red eye which may be either of
      long-standing or of sudden onset. Causes of this redness range from those of a
      relatively minor nature to infection of such severity that it threatens the
      patient's sight. This paper describes the specific aspects of the history to be
      obtained and the examination to be undertaken in these cases. A comprehensive
      review is provided of the various causes of red eye in the contact lens wearer.

PMID- 16303369
TI  - The oxygen performance of contemporary hydrogel contact lenses.
AB  - The oxygen performance of a hydrogel contact lens is arguably its most important
      property when considering the possible physiological response of the eye.
      However, information about this aspect of a contact lens can frequently be
      difficult to obtain, and there are numerous pitfalls in the interpretation and
      application of the available data. This paper presents the oxygen permeability
      and oxygen transmissibility of 17 different lens types as measured by one
      technician in one laboratory across a short time interval. The clear relationship
      between water content and oxygen permeability is confirmed, and the
      transmissibilities of three lens types across a wide power range are reported.

PMID- 16303370
TI  - pH of multipurpose contact lens solutions over time.
AB  - The pH of nine different brands of multipurpose contact lens solutions available
      in Spain was determined over a period of 32 days after opening the bottles. Five
      bottles of nine solutions were used, each of which was buffered and obtained from
      different manufacturers. The pH measurements were taken using a micropH 2002
      Crison pH-meter (accuracy +/- 0.001 pH units). Each solution was measured three
      times daily over the test period using 10-ml samples taken from the same
      container. Fluctuations in pH over time were observed but these were within the
      range of ocular comfort. The average pH of all the solutions tested proved to be
      between 6.99 and 7.56.

PMID- 16303371
TI  - Evaluation of a self-prepared cotton thread test (SP-CTT) and the Phenol Red
      Thread (PRT) test.
AB  - Two cotton thread tests (a self-prepared cotton thread test (SP-CTT) and the
      Phenol Red Thread (PRT) test) were performed on 46 dry eye and 37 normal Hong
      Kong (HK)-Chinese, all subjects being diagnosed by ophthalmologists in a private
      clinic. The mean SP-CTT value for the dry eye subjects (mean +/- SD: 6.2 +/- 4.2
      mm/15s) was significantly lower than that of the normal subjects (8.3 +/- 4.3
      mm/15s). However, no significant difference in the mean PRT value was found
      between the two groups (dry eye subjects: 10.7 +/- 4.5 mm/15s; normal subjects;
      11.4 +/- 4.5 mm/15s). The specificity and sensitivity of the SP-CTT were 78.4%
      and 45.7 when a cut-off value of < or = 4 mm was used, and 56.8% and 65.2% when
      the cut-off value was changed to < or = 6.5 mm. Our results showed that the
      specificities and sensitivities of both tests were poor when applied to these dry
      eye patients.

PMID- 16303372
TI  - Refractive index of rigid contact lens materials.
AB  - A simple hand-held refractometer was used to measure the refractive index of 27
      rigid gas permeable contact lens materials. As a general rule, lenses with
      refractive indices lower than 1.458 are made from fluorosilicone acrylates;
      lenses with refractive indices in the range of 1.458 to 1.469 are made from
      either fluorosilicone acrylates or silicone acrylates; and lenses with refractive
      indices greater than 1.469 are made from silicone acrylates. It is demonstrated
      how refractometry can be used by contact lens practitioners for the
      identification and verification of rigid contact lenses.

PMID- 16303373
TI  - Contact lens wear and diabetes mellitus.
AB  - An estimated 30,000 diabetic patients in the United Kingdom currently wear
      contact lenses. Anecdotal clinical experience indicates that such patients have
      an increased risk of developing potentially sight-threatening ocular
      complications such as ulcerative keratitis. The corneal complications associated
      with diabetes, for example structural changes in the epithelial and endothelial
      cells, have led to some controversy regarding the suitability of contact lenses
      for diabetic patients. There have been few published studies documenting the
      ocular response of the diabetic eye to current generation contact lens materials.
      The purpose of this paper is to review the anterior eye manifestations of
      diabetes and to discuss how such changes could influence contact lens wear.

PMID- 16303374
TI  - Editorial.

PMID- 16303375
TI  - A history of oxygen permeability.

PMID- 16303376
TI  - The effect of rigid lens design on fluorescein fit.
AB  - This paper describes an evaluation of rigid lens design undertaken using a
      computer spreadsheet-based model of fluorescein fit. The study systematically
      varied rigid lens parameters and corneal topography while monitoring the
      following key aspects of lens fit. percentage area of apparent corneal alignment,
      average tear layer thickness and edge clearance. The effect of changes in corneal
      curvature, corneal asphericity, astigmatism, back optic zone radius, back optic
      zone diameter and peripheral radii were evaluated. The findings enable a clearer
      understanding of the relationship between corneal topography, rigid lens
      parameters and rigid lens fit.

PMID- 16303377
TI  - Soft contact lens care systems and corneal staining in Hong Kong-Chinese.
AB  - One hundred and ninety two patient files (for the year September 1995-September
      1996) from the Contact Lens Clinic of The Department of Optometry & Radiography,
      The Hong Kong Polytechnic University were surveyed. A total of 117 patients
      mostly using three lens care systems (CIBA VISION AOSept, Allergan Oxysept 1-step
      and Bausch & Lomb Multipurpose solution (MPS)) were included in this
      retrospective study of the incidence of corneal staining in patients using
      different lens care systems. The incidence and severity of staining observed was
      significantly higher and worse respectively in patients using MPS than in
      patients using the peroxide systems. Corneal staining was observed in 32.3% of
      the patients using AOSept, in 17.8% of the patients using Oxysept 1-step, and in
      70.7% of the patients using MPS system. However, these percentages did not take
      into account other factors (which we assumed to be affecting the three groups
      equally) which may have caused some of the corneal staining observed. Of the
      patients who had corneal staining: 31% (9/29) of the patients using MPS system
      changed to peroxide system, and 38% (11/29) of the patients were re-educated on
      proper lens care; 77% (14/18) of the patients using the peroxide systems did not
      use proper care procedures. The tear stability and volume of HK-Chinese have been
      reported to be low compared to those reported for Caucasians, which may render
      Hong Kong-Chinese soft contact lens wearers more prone to adverse reactions to
      preservatives and to rapid deposit formation. The majority of the patients with
      corneal staining did not complain of any ocular discomfort even when severe
      staining was observed.

PMID- 16303378
TI  - Observation of deposits on disposable contact lenses by bio-, light and scanning
      electron microscopy.
AB  - There has been little published on the presence of deposits on disposable
      hydrogel contact lenses. The purpose of the present study was to determine the
      possible existence of such deposits. Seventy-two disposable lenses (polymacon;
      FDA group 1; non-ionic, low water contact lenses) were fitted to six patients and
      replaced weekly in the course of a total follow-up period of six weeks. By means
      of biomicroscopy, light microscopy and scanning electron microscopy, different
      types of deposits were observed on all the lenses studied. Our results also
      indicate that the accumulation rate of these deposits expressed as a percentage
      of the total area of the lens which they covered increased after the third
      replacement of the lenses over the 4th, 5th and 6th weeks. Finally, we observed
      that the amount of deposits varies in the different patients studied in the
      course of a 6 week follow-up period.

PMID- 16303380
TI  - Editorial.

PMID- 16303379
TI  - The influence of eye movement on soft contact lens visual performance.
AB  - An apparently undocumented aspect of the correction provided by soft hydrophilic
      contact lenses, either at the fitting stage or in wear, is the influence of eye
      movement on visual performance. Using a televised visual discrimination task both
      spectacle (control) and soft contact lens (experimental) monocular visual
      performance was assessed in a group of human subjects (N = 5) under conditions of
      stationary fixation and subsequent to a defined 15 deg ocular excursion. For this
      subject group, analysis of variance revealed no statistically significant
      difference (P > 0.9) between visual performance under the control and any of the
      experimental conditions: the group psychometric functions were similar in all
      cases, regardless of the direction--or absence--of a deliberate eye movement. It
      is concluded that even in new and inexperienced soft contact lens wearers,
      provided that the lens fit is optimum, eye movement does not have a significant
      influence on the visual performance of the eye/lens system.

PMID- 16303381
TI  - Disruption of the tear film by the application of small drops of saline and
      surfactant.
AB  - The effects of disrupting the tear film by placing 5 or 10 microl drops of saline
      and mild surfactant solution (SS) directly onto the tear films of 10 subjects
      were observed and are described here. Disruption of the tear film was only
      transient, with restoration of the film occurring within about two to three
      blinks for saline drops, and four to six blinks for SS drops. When a drop of SS
      was placed on a cornea, two types of black spots/areas may be observed: black
      areas apparently similar to those observed in the TBUT test, and black areas
      forming outside the border of the pattern of the spreading SS drop. In general,
      staining of the black areas formed in the fluorescein-stained tears did not occur
      even when blinking was inhibited for up to 13 s. Stained areas on the corneal
      surface did not have a tendency to form black spots first; the tear film over
      these areas did not appear to be less stable than on other areas of the corneal
      surface.

PMID- 16303382
TI  - Amoebicidal activity of a preserved contact lens multipurpose disinfecting
      solution compared to a disinfection/neutralisation peroxide system.
AB  - The amoebicidal activity of a contact lens multipurpose disinfecting solution
      (MPDS) containing polyquaternium-1 and myristamidopropyl dimethylamine was
      compared to a disinfection/neutralisation peroxide system against Acanthamoeba
      castellanii and Acanthamoeba polyphaga trophozoites and cysts. A quantitative
      microtitre method was used to evaluate the solutions. The MPDS showed similar
      amoebicidal activity to the disinfection/neutralisation peroxide system against
      the trophozoites of both species and equal or more rapid activity against the
      cysts of both species.

PMID- 16303383
TI  - A new rigid gas-permeable semi-scleral contact lens for treatment of corneal
      surface disorders.
AB  - Some extreme corneal irregularities cannot be treated adequately with corneal
      contact lenses. For such cases a rigid semi-scleral lens can be prescribed. We
      evaluated the use of a highly gas permeable rigid semi scleral lens in patients
      with diseased corneas for whom conventional contact lens strategies had failed.
      Twenty two patients (29 eyes) were successfully fitted with individually
      manufactured semiscleral lenses. Corneal hypoxia, which has previously limited
      the use of polymethylmethacrylate (PMMA) scleral contact lenses, did not occur.
      The semi scleral lenses were well tolerated. Two cases were selected to
      illustrate the fitting of these lenses.

PMID- 16303385
TI  - Editorial.

PMID- 16303384
TI  - Has the introduction of multi-purpose solutions contributed to a reduced
      incidence of Acanthamoeba keratitis in contact lens wearers? A review.
AB  - This review paper considers hypotheses for the apparent reduction in incidence of
      Acanthamoeba keratitis over the last 2 years. Investigating such a reduction has
      been facilitated by the performance of an accurate measurement of the incidence
      of this infection amongst contact lens wearers in the West of Scotland at 1:6750
      soft lens wearers annually in 1994 and 1995, the infection did not occur in
      wearers of rigid or gas permeable lenses nor in those avoiding wear of a contact
      lens. The reduction in frequency of presentation of this infection anecdotally in
      Scotland in 1996 and 1997 is supported by a retrospective survey in England,
      although this method of assessing incidence historically is open to error. A new
      survey by the Royal College of Ophthalmologists should, in due course, present
      another accurate incidence figure for 1997/98. The reason for the apparent
      decline in incidence of Acanthamoeba keratitis is believed to be due to the
      introduction by industry over the last 3 years of sterile multipurpose (cleaning
      and disinfecting) solutions (MPS) containing polyhexamethylene biguanide to
      achieve their current popularity. This situation is mirrored by that in the
      United States when the introduction of MPS is thought to have reduced their
      incidence rate of Acanthamoeba keratitis following the outlawing of contact lens
      storage in home made saline, using water contaminated with Acanthamoeba.

PMID- 16303386
TI  - Analysis of the repeatability of tear break-up time measurement techniques on
      asymptomatic subjects before, during and after contact lens wear.
AB  - This study assessed the repeatability of various methods of measuring tear break
      up time (TBUT) with and without soft contact lenses (CLs). TBUT was measured on
      22 subjects with the tearscope, videokeratoscope and slit-lamp before and after
      30 min of soft CL wear, and immediately after CL removal. Slit-lamp corneal TBUT
      was measured with fluorescein and without fluorescein while wearing CLs. TBUT was
      measured three times on the right eye only, using each technique in randomised
      order. TBUT measurements on CLs were repeated a second day. TBUT measurements
      were highly variable under all conditions and our results indicated a lack of
      correlation between techniques. The videokeratoscope was the least repeatable;
      while the tearscope was the most repeatable technique.

PMID- 16303387
TI  - Comparing the extent of protein build-up on several disposable lenses by two
      spectrophotometric methods.
AB  - This study aims to quantify levels of protein build-up on high-water ionic (Type
      IV) disposable contact lenses worn by patients, by two spectrophotometric
      methods, previously validated only with conventional lenses. Forty lenses were
      analyzed and the related results were compared. The Ninhydrine-Lysozyme method
      and the Coomassie Blue Albumin one agreed in identifying the most spoiled lenses.
      Etafilcon A attracted significantly more protein than the other materials tested,
      which were in the following decreasing order of protein spoilation: Ocuflcon D,
      Ocufilcon A and Vasurfilcon A. These similar findings suggest that it is possible
      to use the above mentioned analysis methods for an accurate evaluation of the
      contamination of several materials of disposable/frequent replacement lenses as
      for conventional lenses.

PMID- 16303388
TI  - A simple technique for measurement of corneal thickness.
AB  - Measurement of corneal thickness has potential benefit both in the fitting of
      contact lenses and in monitoring any pathology that could affect corneal
      thickness. Corneal thickness measurement is undertaken using an accessory to the
      biomicroscope, the optical pachometer, or by means of expensive apparatus such as
      the ultrasonic pachometer. There are other complex methods, such as laser Doppler
      interferometry, or ultrasonic rasters of the cornea. In this study, an easier and
      low cost method, based on the measurement of the optical section formed of the
      cornea by the biomicroscope illumination system, is proposed. The advantages of
      this new method are the simplicity of its experimental set-up which consists of a
      calibrated graticule in an eyepiece of the biomicroscope, the speed of the
      measurement which increases with practice and the low cost, due to the fact that
      the biomicroscope is standard equipment in the ophthalmic consulting room.

PMID- 16303389
TI  - A search for differences in size perception of near objects in young myopes
      corrected by either spectacles or contact lenses.
AB  - Accommodation and convergence demands are lower for a spectacle-corrected myope
      than for the same individual when corrected with contact lenses. Thus the impact
      of accommodative/convergence micropsia ought to be lower with the spectacle
      correction. A size-matching experiment which required myopic subjects
      (corrections up to -12.25 D) to match the sizes of each of four standard targets
      with a variable comparison target was therefore conducted. The standard targets
      were placed at four viewing distances: 3 m, I m, 0.5 m and 0.25 m. All standard
      targets subtended 2 degrees at the eye. The variable comparison target was
      situated at a fixed distance of 2 m and was generated on a visual display unit.
      Each of the eight subjects was shown one standard target at a time under
      binocular viewing conditions and was told to adjust the size of the comparison
      target until he/she felt that both targets were equal in linear size. Two sets of
      readings were taken: one when the subject's myopia was corrected with spectacles
      and one when corrected with contact lenses. No systematic difference in size
      perception was found between the spectacle and contact lens corrected cases,
      implying that the relatively small differences in accommodation and convergence
      demand did not significantly influence the size judgements.

PMID- 16303390
TI  - Contact lens fitting in the United Kingdom.

PMID- 16303391
TI  - Editorial.

PMID- 16303392
TI  - Current developments in measurement of corneal topography.
AB  - Significant developments in the measurement of corneal topography have taken
      place since the early Placido devices. These developments have arisen as a result
      of two key factors: increased computer processing power and also improved
      algorithms that are capable of deriving corneal shape without making any
      fundamental assumptions. These developments are reviewed and attention is drawn
      to some of the key areas where current topographical devices are somewhat
      limited.

PMID- 16303393
TI  - The use of digital image capture in contact lens practice.
AB  - The present decade has seen the introduction of digital imaging systems to a
      number of medical environments, including contact lens practice. During the past
      year, the authors have used two anterior segment video-based digital image
      capture systems. These systems allow instantaneous image capture and have both
      diagnostic value to practitioners and educational value to patients. This paper
      discusses and clarifies the terminology that surrounds such systems and looks
      carefully at the advantages and disadvantages when compared to more traditional
      35 mm photography in particular with reference to image colour, resolution and
      storage. The difference between video digital image capture and the more recently
      available digital camera image capture is also discussed. The value of digital
      imaging is shown by a series of images from the authors' archives.

PMID- 16303394
TI  - Non-invasive Tearscope Plus routine for contact lens fitting.
AB  - The Keeler Tearscope Plus was invented by the author as a multi-use instrument
      for the non-invasive examination of the tear film, its appearance, volume,
      stability and, its effect on the ocular and contact lens surface. Its use is
      maximised by following a step-by-step approach described which is based on simple
      clinical principles of tear film stability.

PMID- 16303395
TI  - Contact lens standards.
AB  - The British Standards Institution (BSI) is in the process of publishing an
      extensive series of standards relating to contact lenses which were originally
      formulated as International and European Standards. Standards specifying
      tolerance limits for the manufacture of rigid and hydrogel lenses have been based
      upon data on reproducibility derived from 'ring tests' in which measurements are
      made by a series of independent operators. Despite publication of an
      International Standard on terminology in 1986, some authors persist in using
      obsolete terms and this practice is deplored.

PMID- 16303397
TI  - A return to primitive practice? Radial keratotomy revisited.
AB  - Recently, a refractive surgeon was quoted in the national and professional press
      as proposing that radial keratotomy (RK) is to be preferred over laser
      procedures, such as photorefractive keratectomy (PRK) and laser assisted in situ
      keratomileusis (LASIK). The rationale for this public recommendation was that the
      RK procedure achieves better visual results and fewer complications than the
      laser procedures. Peer reviewed literature on these refractive procedures was
      surveyed to establish the validity of such a statement and it was found that
      current data do not support the notion that RK results in better visual outcomes
      than PRK and LASIK The true incidence of complications is difficult to establish.
      However, when the post procedure chronic effects are compared between RK, PRK and
      LA SIK, it becomes apparent that the post-RK patient pays the highest price, by a
      large margin, in visual quality impairment and corneal health. Although the
      visual acuity outcomes for low to moderate myopes, when corrected by any of the
      three refractive procedures considered here, are not dramatically different, we
      concluded that RK is not the preferred methodology because of its associated
      chronic visual and corneal health complications.

PMID- 16303398
TI  - Corneal surface temperature decreases with age.
AB  - Infrared temperature measurement has found numerous applications in the detection
      and diagnosis of ocular and systemic disease. In the study of ocular temperature
      it is important to consider all parameters which might influence recorded
      measurements. Examples of such parameters include room temperature, time of day
      and age of subject. This communication discusses the effect of age on ocular
      temperatures measured with a modern, wide field, colour-coded infrared detector.
      It is demonstrated that ocular surface temperature decreases by -0.010 degrees C
      per year throughout life, although the rate of change increases after middle age.

PMID- 16303399
TI  - The parameter stability of a high dk rigid lens material.
AB  - The use of rigid materials with high oxygen permeability (Dk) is on the increase,
      their major benefit being the reduction of hypoxia. However, there is a
      reluctance to use these materials possibly due to increased surface scratching,
      reduced wettability, increased deposition, reduced life expectancy and parameter
      instability. Considering parameter stability, various studies have demonstrated
      contradictory results or used high Dk materials based on the silicone acrylate
      polymer. This study was designed to investigate whether the parameters of a high
      Dk rigid fluorocarbon contact lens material changed during daily wear and
      extended wear schedules. Thirty five subjects, divided into group groups, Group I
      wore the lens on a daily wear basis, whereas those in Group II wore the lens on a
      monthly extended wear basis. The parameters and integrity of the lenses were
      monitored in both groups every 3 months. For lens integrity a statistically
      significant increase in surface scratching was demonstrated for the lenses worn
      by the subjects of both groups over the time of the study (Group I, F=7.990, P
      <0.0001 [ANCOVA]; Group II, F=6.241, P=0.003 [ANCOVA]). The only parameter to
      show a statistically significant variation over the study period was that of
      centre thickness for the lenses worn by the subjects in Group I (F=3.976,
      P=0.0063 [ANCOVA]), with a mean reduction in centre thickness of 0.022 mm at the
      12 month visit. No change was noted for either group or between groups for the
      other parameters measured. This study demonstrates that the parameters of rigid
      contact lenses manufactured from high Dk fluorocarbons are stable with only a non
      clinically significant reduction in centre thickness for the contact lenses worn
      by the subjects in Group I.

PMID- 16303400
TI  - A novel method to quantify the edge contour of RGP contact lenses.
AB  - A new method of accurate profile measurement of rigid gas permeable lenses and
      edges is described. A purpose built optical profilometer non-destructively scans
      complete cross-sections in several meridians of any rigid lens. The accuracy of
      the instrument was verified to be better than +/-2.5 microm. The profile data are
      obtained and stored in digital format for further analysis. The seven most
      commonly used edge features were defined by means of mathematical algorithms to
      extract unique numerical values for these parameters from the measured profiles.
      Applications of the new edge quantification method in clinical contact lens
      research and manufacturing quality control are shown.

PMID- 16303401
TI  - The 'O' sign presentation of a lost rigid contact lens.

PMID- 16303405
TI  - The case for conducting clinical research in contact lens practice.

PMID- 16303402
TI  - Complacency regarding the risks of Acanthamoeba keratitis.

PMID- 16303406
TI  - Population-based cohort study of microbial keratitis in Scotland: incidence and
      features.
AB  - OBJECTIVE: To investigate the incidence and features of bacterial, fungal and
      protozoal keratitis in Scotland. DESIGN: Prospective, population-based cohort
      study of all persons who developed culture proven microbial keratitis over an 8
      month period. SETTING: West of Scotland, UK. SUBJECTS: Approximately 3,000,000
      population. MAIN OUTCOME MEASURES: Incidence and risk factors for microbial
      keratitis. METHODS: All patients were included who had presumed microbial
      keratitis from which bacteria, fungi or Acanthamoeba was isolated from the
      corneal scraping by the hospital laboratory using a standardised protocol. In
      addition, contact lens wearing patients with pathognomonic features of
      Acanthamoeba keratitis, who yielded a negative culture result when referred on
      chlorhexidine therapy, were included if Acanthamoeba could be cultured from their
      lens storage case. RESULTS: The overall annual incidence of culture-proven
      microbial keratitis was 0.26 per 10,000 with a rate of 1.8 per 10,000 for contact
      lens wearers (all types, soft and rigid). Based on a previous pilot study of
      'presumed' microbial keratitis in Glasgow, it was possible to estimate the
      incidence of expected 'presumed' microbial keratitis as 0.36 per 10,000 overall
      and 2.44 per 10,000 for contact lens wearers (all types). The incidence for
      Acanthamoeba keratitis was 1.49 per 10,000 soft contact lens wearers; this
      infection was not detected in the absence of contact lens wear nor with use of
      gas permeable or rigid contact lenses. CONCLUSIONS: 'Presumed' microbial
      keratitis from all causes, in the adult population, was approximately three times
      less common in the West of Scotland (0.36 per 10,000) than would be expected from
      a comparable retrospective study from Minnesota, USA for the years 1980-1988 (1.1
      per 10,000). It was rare (approximately one case expected in 2 million per year)
      in the absence of pre-existing corneal disease, cosmetic contact lens wear or
      trauma. Ocular surface disease was the underlying cause predisposing to infection
      in 58% of cases, with an incidence of 'presumed' keratitis of 0.21 per 10,000
      population; the highest incidence was found in the elderly population. Contact
      lens wear was responsible for 38% of cases, emphasising the importance of
      preventive hygiene and effective disinfection in this group. The estimated
      incidence of 'presumed' microbial keratitis in the West of Scotland associated
      with cosmetic wear (daily and extended use) of soft contact lenses was
      significantly less (P<0.05) than that expected from a prospective study in New
      England, America in 1985 (266 per 10,000, rather than 8.05 per 10,000). However,
      the estimated incidence for presumed microbial keratitis for the West of Scotland
      associated with wearing soft contact lenses for cosmetic purposes in the daily
      wear modality (266 per 10,000) was less, but not significantly less, than that
      found in the prospective American study (4.20 per 10,000). The daily wear mode
      for contact lenses is almost universal in the West of Scotland, where extended
      wear has never been recommended. Extended wear has been shown in the USA to be
      associated with an incidence of presumed microbial keratitis between five and ten
      times higher than that associated with daily wear. This explains the lower
      incidence we have observed and a difference with the US study for overall
      infection rates but not when associated with daily wear alone. The incidence of
      proven Acanthamoeba keratitis found in the Scottish study among wearers of soft
      contact lenses for daily wear cosmetic purposes was exceptionally high at 1.49
      per 10,000.

PMID- 16303407
TI  - Acanthamoeba keratitis in Scotland: risk factors for contact lens wearers.
AB  - OBJECTIVE: To investigate risk factors for Acanthamoeba keratitis amongst contact
      lens wearers in Scotland. DESIGN: Patients with Acanthamoeba keratitis in the
      Scottish study, all of whom wore contact lenses, were compared with 46 healthy
      asymptomatic contact lens-wearing controls. They were all visited at home for
      contact lens and environmental microbiological sampling. In addition, all 288
      optical practices in the West of Scotland were polled for contact lens types and
      disinfecting solutions sold in 1995, and a sample, each of whom fitted more than
      500 contact lenses per year, were polled for a second time. Independently, a poll
      was commissioned by the Eyecare Information Service in July/August 1995 to
      estimate the numbers of contact lens wearers in Scotland and the UK. Industry was
      polled for numbers of each contact lens disinfecting regimen sold in Scotland in
      1995. SETTING: West of Scotland, UK. SUBJECTS: All contact lens wearers among the
      3 million population of the West of Scotland Health Board Areas. MAIN OUTCOME
      MEASURES: Risk factors for Acanthamoeba infection and recommendations for its
      prevention. RESULTS: When Acanthamoeba infection occurred, patients' home water
      systems were frequently (54%) found to be colonised by this amoeba. Patients more
      frequently washed their storage cases in tap water than controls (P<0.05) with
      resulting contamination, kept storage cases wet rather than air drying them
      (P<0.05), and had coliform bacteria cultured from the storage case (P<0.05) and
      had viable Acanthamoeba within the storage case (P<0.0001). Overall, patients
      were found to have significantly more risk factors than controls (P<0.0001). The
      noncompliant use of chlorine tablet disinfection, or failure to disinfect contact
      lenses at all, was associated with increased risk (P<0.05). Ionic high water
      content contact lenses (FDA group 4 material), when used without disinfection or
      with non-compliant use of low chlorine (Soflab) tablet-based disinfection, were
      associated with increased risk of Acanthamoeba infection (P<0.05). In log-linear
      modelling of risky hygiene behaviours associated with contamination of storage
      cases with Acanthamoeba, the most significant behaviour was found to be use of
      the less effective disinfection methods (chlorine tablets or no disinfection).
      However further investigation showed that these methods were associated with an
      increased probability of rinsing the storage case in tap water, so that these two
      behaviours are confounded in the group studied. CONCLUSIONS: Failure to disinfect
      contact lenses, non-compliant use of chlorine tablets and/or introduction of tap
      water rinsing of storage cases were associated with increased risk of
      Acanthamoeba infection. New multipurpose solutions and hydrogen peroxide gave the
      lowest risk of Acanthamoeba infection, with no statistically significant
      difference between them. Ionic high-water content (FDA group 4) contact lenses
      were at increased risk of being associated with Acanthamoeba keratitis if used
      without effective disinfection (multipurpose solutions or hydrogen peroxide). The
      use of domestic tap water for contact lens and storage case hygiene must be
      avoided, as a chain-of-causation' was identified from the home water supply.

PMID- 16303409
TI  - Contact lens back surface specification derived from the EyeSys videokeratoscope.
AB  - Rigid corneal lenses were designed for 36 subjects using the software available
      with the EyeSys Corneal Analysis System 2000 (software version 2.00W) and a
      program from the textbook 'Contact lens Optics and Lens Design' Both alignment
      and apical clearance designs were investigated. It was found that the EyeSys
      lenses produced tear layer thickness and axial edge clearance values that were
      excessive in some cases, especially for flatter corneas. In the case of an
      alignment mode of fitting, the designs were relatively steep in the back optic
      zone and flat in the periphery when compared with designs derived from the
      textbook.

PMID- 16303410
TI  - Antibacterial and antifungal effects of soft contact lens disinfection solutions.
AB  - AIMS: To study the antibacterial and antifungal effects of soft contact lens
      disinfection solutions. METHODS: Eight contact lens disinfection solutions
      containing hydrogen peroxide or biguanides or polyquad compounds were evaluated
      with respect to their ability to disinfect a saline solution experimentally
      contaminated with different bacteria and with a fungus. We used cultures in blood
      Agar, MuellerHinton agar and Saboureaud's agar to identify the bacterial and
      fungal growth following 14 h of exposure to the disinfection solutions. RESULTS:
      Hydrogen peroxide, DYMED and polyhexamide solutions prevented the growth of the
      four bacteria studied. The solution containing biguanide prevented the growth of
      Escherichia coli and Staphylococcus epidermidis. The solution with polyquad
      solution only prevented the growth of Staphylococcus epidermidis and none of the
      disinfection solutions prevented the growth of Candida albicans. The control
      solution, which was saline, did not prevent the growth of either bacteria or
      fungi. CONCLUSIONS: Disinfection solutions containing hydrogen peroxide, or DYMED
      or polyhexamide can disinfect these four bacteria but none of them prevented the
      growth of Candida albicans.

PMID- 16303411
TI  - The use of hybrid lenses in management of the irregular cornea.
AB  - The use of SoftPerm hybrid lenses was investigated as part of a 10 year
      retrospective audit of keratoconus in the Contact Lens Service at Nottingham
      University Hospital which serves a population of approximately one million.
      During this period, nine patients (14 eyes) were fitted with SoftPerm a lenses
      for keratoconus. Two further patients (two eyes) were included with a diagnosis
      of irregular astigmatism and one patient (one eye) was fitted post-corneal graft.
      Seven patients were regarded as successful hybrid lens wearers and five were
      regarded as unsuccessful wearers. Of the unsuccessful cases, one patient managed
      satisfactorily using a rigid gas permeable corneal on the unaffected eye, two
      patients subsequently had successful corneal grafts, one patient continued with
      restricted rigid gas permeable lens wear and one patient defaulted.

PMID- 16303412
TI  - The reproducibility of videokeratoscope measurements as applied to the human
      cornea.
AB  - To be useful in contact lens fitting, the videokeratoscope (VK) must be able to
      provide the practitioner with credible data on the vertex radius and central
      topography, or 'shape, of the patient's cornea. For this purpose, it is desirable
      that the measured value of the former should be credible at the level of 0.05 mm.
      In order to examine the accuracy, repeatability and reproducibility of the
      corneal dimensions provided by the videokeratoscope, eight eyes were measured on
      four different EyeSys systems at four independent sites. The order of measurement
      was random at each site. This amounted to a balanced uniform-level precision
      experiment ('ring test') of the VK instruments as defined in International
      Standard ISO 5725. The resulting data were analysed using the statistical
      procedures given in this Standard to provide a formal statement of the
      measurement precision of the EyeSys VK system. Based on this study, the estimated
      measurement precision of the EyeSys videokeratoscope as applied to the latter
      principal meridian of the normal human cornea is: Vertex radius: repeatability
      standard deviation, S(R)=0.0805, reproducibility standard deviation, S(R)=0.1041.
      p value: repeatability standard deviation, S(r)=0.0473, reproducibility standard
      deviation, S(R)=0.0574. The estimated measurement precision for the steeper
      principal meridian is: Vertex radius: repeatability standard deviation,
      S(r)=0.0771; reproducibility standard deviation, S(R)=0.1015. p value:
      repeatability standard deviation, S(R)=0.0698; reproducibility standard
      deviation, S(R)=0.0749.

PMID- 16303414
TI  - Disinfecting action of a new multi-purpose disinfection solution for contact
      lenses.
AB  - The disinfection activity of a new multipurpose disinfection solution (OPTI-FREE
      Express with ALDOX) was compared to several other contact lens disinfecting
      solutions. The new solution is preserved with polyquaternium-1 and
      myristamidopropyl dimethylamine. The other solutions included 3% hydrogen
      peroxide systems and multipurpose solutions (MPS) preserved with
      polyhexamethylene biguanide. The products were tested for antimicrobial activity
      against Staphylococcus spp., Pseudomonas aeruginosa, Serratia marcescens, Candida
      albicans, Fusarium solani, and Aspergillus fumigatus. OPTI-FREE Express provided
      a broader range of antimicrobial activity than the MPS. It provided activity
      similar to that demonstrated by 3% hydrogen peroxide systems, but unlike the
      hydrogen peroxide system tested, it also prevented re growth of the organisms
      during extended storage.

PMID- 16303415
TI  - Adherence of Acanthamoeba to human corneal epithelial cells recovered from normal
      non-lens wearers and asymptomatic contact lens wearers.
AB  - To increase our knowledge of factors leading to Acanthamoeba keratitis in contact
      lens wearers, we determined the ability of this organism to adhere to corneal
      epithelial cells (EC) recovered from non-lens wearers (NL) and from subjects
      using hydrogel contact lenses on a daily (DW) and extended wear (EW) schedule.
      ECs were incubated with trophozoites of Acanthamoeba and, after 3 h, the median
      per cent of cells exhibiting adherence was 24, 23 and 23 for NL, DW and EW groups
      respectively (P=0.552, Kruskal-Wallis Test). There were no differences between
      the groups for the number of adherent amoebae and a significant majority had only
      one adherent trophozoite per EC. No difference in adherence was seen with
      increasing exposure time. Factors other than amoebic adherence to superficial
      corneal EC are responsible for the increased incidence of Acanthamoeba keratitis
      in lens wearers.

PMID- 16303416
TI  - Re-wetting, comfort, lubricant and moisturizing solutions for the contact lens
      wearer.
AB  - In recent years there have been significant changes in perspective and
      availability of eyedrops designed to provide comfort to the contact lens wearer.
      This review addresses the reasons why there is a need for these types of products
      and considers their potential impact on the corneal and conjunctival surface. The
      methods of assessment of these solutions are discussed and the range of current
      products and options for the UK practitioner are detailed.

PMID- 16303419
TI  - Contact lens fitting in high degree myopia.
AB  - Advantages and disadvantages of both spectacle and contact lens correction of
      high degree myopia are reviewed. Pertinent aftercare problems in this group of
      patients are discussed. Aspects of contact lens wear with regard to the eyelids
      are described. Soft contact lens problems are discussed in relation to the
      greater thickness of lenses of high power. Guidelines are provided for the
      fitting of rigid gas permeable and of soft contact lenses for this patient group.
      Other factors are explored in lens fitting such as over-refraction, near vision
      and practitioner costs. Recommendations are given for advising on lens care and
      aftercare.

PMID- 16303417
TI  - Process capability measurement of frequent replacement spherical soft contact
      lenses.
AB  - Frequent replacement soft contact lenses must have good reproducibility in order
      to avoid clinical problems arising from manufacturing variations in lens
      parameters. This study assessed the actual and potential process capability of
      eight frequent replacement lenses (monthly or 2-weekly replacement) in relation
      to back vertex power, back optic zone radius, total diameter and centre
      thickness. Twenty-four lenses in three powers (-1.00, -3.00, -6.00 D) were
      measured for eight frequent replacement lenses: Acuvue, Acuvue 2, Biomedics 55,
      Encore, Focus, Optima FW, Soflens 66, Surevue. In general, the lenses showed
      adequate reproducibility in respect of those parameters likely to affect lens
      fit, namely back optic zone radius, total diameter and centre thickness. The
      process capability results showed some variation in reproducibility of BVP
      between lens types and between lens powers. Process capability was found to be a
      useful measure of contact lens reproducibility.

PMID- 16303420
TI  - The challenge of fitting astigmatic eyes: rigid gas-permeable toric lenses.
AB  - It is generally acknowledged that rigid gas permeable lenses (RGP) afford
      superior visual correction of the ametropic eye compared with hydrophilic lenses.
      However, there are occasions when a spherical rigid lens will not provide an
      acceptable result in terms of fitting or vision on astigmatic eyes. In these
      instances a toric RGP lens will be required. This paper deals with the
      definitions, indications, fitting technique, calculations and designs relating to
      this modality of fitting. Whilst often perceived as a complex area within contact
      lens practice, the basic optics and fitting of toric RGP lenses is not overly
      difficult. A simple empirical means of fitting the lenses will be described which
      has a high 'First-fi' success rate.

PMID- 16303421
TI  - Therapeutic contact lenses.
AB  - The indications for therapeutic contact lenses and details some of the more
      commonly encountered conditions where they have proved to be of great benefit are
      reviewed. A brief overview is given of the lens material and designs currently
      available in this field and advice on the management of patients requiring this
      type of lens modality.

PMID- 16303422
TI  - The unique role of scleral lenses in contact lens practice.
AB  - The advantages and disadvantages of scleral lenses are reviewed. The indications
      for scleral lenses are cases where other types of contact lens fail to provide a
      satisfactory result. In other cases, the intrinsic nature of scleral lenses makes
      them the modality of first choice. Both the traditional approach to fitting
      scleral lenses and the procedures for fitting contemporary gas permeable designs
      are described.

PMID- 16303424
TI  - The why and wherefore of soft lens visual performance.
AB  - Although significant advances have been made over the past decades in improving
      the physiological performance of hydrogel lenses, little has been done to
      understand and improve the quality of vision experienced by soft lens wearers.
      Yet, almost since their inception, the literature has revealed numerous reports
      claiming that soft lenses provide inferior visual performance compared to
      spectacles or rigid contact lenses. This paper outlines those physical,
      physiological and optical factors which may be responsible for less than optimum
      soft lens vision, and describes the results of a series of investigations
      designed to pinpoint the most probable culprit in soft lens designs typically
      used by today's clinician. The results of these studies will provide the
      clinician with a better understanding of the contact lens/ocular environment
      interactions which affect soft lens visual performance and a guide to solving
      their soft lens patients day-to-day vision problems.

PMID- 16303425
TI  - Ultraviolet transmittance of the Vistakon disposable contact lenses.
AB  - With increasing scientific evidence demonstrating the harmful effects of
      ultraviolet (UV) radiation on different ocular tissues, contact lens
      manufacturers are incorporating UV blocking monomers into their contact lenses.
      This study evaluated the transmittance spectra of Vistakon's disposable soft
      contact lenses (1 Day Acuvue, Acuvue, Surevue, and Vistavue). All except Vistavue
      contain a UV blocking agent. Transmittance for each lens was recorded from 200 to
      400 nm on a Shimadzu UV 160U Dual Beam Recording Spectrophotometer. The results
      indicate that lenses which incorporate the UV blocking monomer significantly
      reduced the transmission of W radiation while untreated lenses did not. Our
      findings indicate that 1 Day Acuvue, Surevue, and Acuvue meet the American
      National Standards Institution (ANSI) Standard Z80.20 for Class 2 UV blockers: a
      maximum of 30% transmittance of UVA wavelengths and 5% transmittance of UVB
      wavelengths. In contrast, the Vistavue lens demonstrated negligible UV blockage.
      Our technique, in which contact lenses were placed directly in front of a
      measuring beam, was accurate and simpler than previously reported methods and may
      be useful in future studies. We found that UV blocking soft contact lenses can be
      a viable alternative for spectacles in protecting internal ocular structures from
      UV radiation. However, the external structures of the eye remain at risk and
      would continue to benefit from the use of UV blocking sunglasses or spectacle
      lenses.

PMID- 16303426
TI  - The influence of water content of hydrogel contact lenses when fitting patients
      with 'tear film deficiency'.
AB  - THe fitting of patients presenting a deficient tear film with hydrogel contact
      lenses offers a challenge to the professional who must choose between materials
      having either a low or a high water content. Conflicting conclusions from
      previous studies concerning the better option led the authors to design a single
      centre, double masked, clinical study. Twenty-six subjects deemed to have 'tear
      film deficiency' were fitted with a low water content hydrogel lens on one eye
      and a high water content one on the other eye. Each subject wore the lenses on a
      daily wear basis (about 10 hours a day) for 30 days. A detailed questionnaire
      about subjective considerations, such as comfort and ocular appearance, was
      completed by the subjects at the end of every day of contact lens wear. The data
      obtained from these questionnaires and those recorded at three follow-up visits
      led to the final conclusions. THe questionnaires showed no statistically
      significant difference between the two eyes in dryness sensation, redness, light
      sensitivity, blurred vision or overall comfort. During the follow-up visits, no
      observed sign showed a clinically significant difference between the two eyes.
      Accordingly, the authors conclude that the water content of hydrogel lens is not
      a key factor when fitting hydrogel lenses to patients with 'tear film
      deficiency'.

PMID- 16303427
TI  - Clinical evaluation of a custom-made toric soft lens.
AB  - PURPOSE: The fitting of toric soft contact lenses is often complicated by
      interference between the toric optics and the geometry need to stabilise the lens
      on the eye. The use of a spherical trial lens to determine the parameters of a
      toric soft contact lens can lead to unintended positioning and movement of the
      lens ordered. The purpose of this study was to evaluate clinically the success.
      PURPOSE: The fitting of toric soft contact lenses is often complicated by
      interference between the toric optics and the geometry needed. METHOD: The design
      of the lenses used was such that optical correction and stabilisation were
      separated. The lenses had a back tonic surface limited to the central optical
      zone and base down prism stabilisation in the periphery. The empirical system
      used corneal radii, spectacle refraction and horizontal visible iris diameter as
      lens design parameters. RESULTS: This multi-centre trial, comprised of 105
      patients (193 eyes), revealed an overall success rate of 86%. The total number of
      lenses ordered to achieve success was 1.46 per eye in new patients and 1.69 per
      eye in patients who were failures with other toric soft lenses. In 14% of the
      cases success could not be achieved despite ordering several lenses (up to 4
      lenses/eye). Many of these patients (60%) were also failures with other toric
      soft lenses. CONCLUSION: It is concluded that in new patients successful toric
      soft contact lens fitting can be achieved with an empirically based method. When
      refitting former toric soft lens failures, we recommend discontinuation after two
      further unsuccessful fittings.

PMID- 16303428
TI  - Trial contact lenses and vCJD.

PMID- 16303430
TI  - Psychological, clinical and commercial perspectives on contact lenses: invisible,
      reliable, profitable.

PMID- 16303431
TI  - Age, stability of the precorneal tear film and the refractive index of tears.
AB  - PURPOSE: To investigate the relationship between age, stability of the precorneal
      tear film and refractive index of tear samples drawn from a normal population.
      METHODS: The stability of the precorneal tear film was estimated by measuring the
      Tear Thinning Time MT) using the Bausch and Lomb keratometer. Microlitre tear
      samples were obtained from the lower tear meniscus using glass capillary tubes.
      The refractive index (RI) was measured using a digital electronic Abbe
      refractometer with an accuracy of +/- 0.00005 units. Measurements were obtained
      from the right eyes of 110 subjects (55 male and 55 female) ranging in age from
      18 to 89 years. They were all healthy, non-contact lens wearing individuals with
      no history of ocular disease or dry eye symptoms. RESULTS: A significant
      relationship was found between age (x) and tear stability (TTT) in both genders.
      Females, TTT = 32.89-0.33x, (Spearman correlation coefficient, r = -0.537, P =
      0.0001). Males, TTT = 29.25-0.29x (Spearman correlation coefficient, r = -0.353,
      P = 0.008). A significant correlation was found between age (x) and refractive
      index (RI) in females only RI = 1.33815-0.000023x, (Spearman correlation
      coefficient, r = -0.299, P = 0.027). CONCLUSION: Tear stability is lower in the
      aged eye regardless of gender. Tear refractive index is lower in the older female
      eye.

PMID- 16303432
TI  - Visual acuity, lens flexure, and residual astigmatism of keratoconic eyes as a
      function of back optic zone radius of rigid lenses.
AB  - The purpose of this study was to determine whether the visual acuity of
      keratoconic eyes was affected by alteration of back optic zone radii (BOZRs) of
      rigid gas permeable lenses (RGP) contact lenses. Visual acuity, spherical and
      sphero-cylindrical over-refraction and keratometry of the front surface of the
      RGP lenses of nine keratoconic eyes were measured. The BOZR of the five lenses
      varied from steeper to flatter than that habitually worn by the subjects. The
      steepest lenses produced significantly greater lens flexure and residual
      astigmatism (P < 0.002) and worse high and low contrast visual acuity with the
      spherical over-refraction (P < 0.05). There was no statistical difference in
      visual acuity across the range of BOZR when a sphero-cylindrical over-refraction
      was applied. Thus reduced visual acuity in keratoconus with steep lenses is
      likely due to uncorrected residual astigmatism from a combination of several
      possible sources.

PMID- 16303434
TI  - The concept of orthokeratology in which corneal lenses are fitted in order to
      temporarily reduce or eliminate a refractive error.

PMID- 16303433
TI  - Clinical performances of two disposable soft contact lenses of different
      materials on Hong Kong-Chinese.
AB  - Dryness due to contact lens wear and poor wetting of contact lenses among contact
      lens wearers is a common observation and contact lens manufacturers have
      introduced new, better quality soft lens materials that are claimed to be more
      deposit resistant, and/or dehydration resistant. The purpose of this study was to
      evaluate and compare the clinical performance of Hydron ActiSoft 60 section sign,
      made of a new material (HyGMAtrade mark) which is claimed to be dehydration
      resistant with excellent wettability, with ActiFresh 400, made of conventional
      non-ionic hydrogel material. The experiment was conducted as a double-masked,
      randomised, cross-over study. Clinical assessment included pre-lens non-invasive
      tear break up time (PL-NITBUT), logMar visual acuity and contrast sensitivity
      (CS). Corneal staining, if any, was recorded at each visit. Subjective ratings in
      regard to dryness, grittiness, lens awareness, vision, comfort, handling
      (removal), handling (cleaning) and the overall preference of each lens type were
      obtained at the end of 3 (Phase A) and 6 months' (Phase B) wear. Twenty-eight
      subjects successfully completed the study. In Phase A, no significant differences
      were found in both baseline PL-NITBUT and PL-NITBUT after wearing the same lenses
      for 1 month between the two lens types. In phase B, baseline PL-NITBUT for
      ActiFresh 400 was significantly shorter than that for ActiSoft 60. However, after
      1 month of wear, the difference in PL-NITBUT between the two lens types was no
      longer significant. PL-NITBUT was significantly reduced after 1 month's wear for
      both ActiSoft 60 and Actifresh 400, and in both Phase A and Phase B. The two lens
      types provided comparable logMAR visual acuity, and there was no significant
      differences in CS (Pelli Robson) between spectacle lens correction (equivalent
      spheres) and either lens type. The incidence of corneal epithelial staining was
      significantly higher and more severe with ActiFresh 400 than with ActiSoft 60,
      both in Phase A and Phase B. Statistically, there were no significant differences
      in the scores to the set of questions listed in the questionnaire between the two
      lens types, except for lens awareness and lens handling. Of the subjects having a
      preference for one lens, more subjects preferred ActiSoft 60 than ActiFresh 400.
      In terms of overall preference of the two lens types, at the end of Phase A, 50%
      of the subjects preferred ActiSoft 60 while only 30% preferred ActiFresh 400, the
      remaining 20% had no preference. However, by the end of Phase B, preferences for
      ActiSoft 60 and ActiFresh 400 were comparable. This appeared to be due mainly to
      the ease of lens handling of the latter.

PMID- 16303435
TI  - Contact lenses in myopia reduction - from orthofocus to accelerated
      orthokeratology.
AB  - Orthokeratology has been used to provide temporary reduction of myopia since the
      1950s and in recent years the development of new lens designs, materials and
      advanced instrumentation for corneal modelling has resulted in a resurgence in
      interest in this procedure. In particular, the reverse geometry design has
      allowed greater myopia reduction. Materials with high oxygen permeability have
      improved the corneal response to rigid lenses and in orthokeratology they allow
      overnight retainer lens wear. Corneal modelling systems allow the orthokeratology
      changes to be monitored and measured, and have increased our understanding of the
      technique. This paper summarises previous published work in this area and
      identifies the uncertainties which still remain.

PMID- 16303436
TI  - Orthokeratology in low myopia. Part 1: efficacy and predictability.
AB  - AIMS: Modern orthokeratology (ortho-k) using reverse geometry lens designs is
      being widely used for myopia reduction world-wide although there has been no well
      controlled clinical trial of this procedure. This paper reports on the efficacy
      and predictability of an ortho-k procedure using the OK-74 lens design (now known
      as OK-704). METHODS: We carried out a 100-day, controlled, randomised clinical
      trial in which 14 subjects underwent ortho-k and a further 14 were fitted with
      aligned rigid contact lenses. RESULTS: The mean reduction in myopia was 1.50 (SD
      0.45) D in the ortho-k group and 0.01 (SD 0.20) D in the control group. Unaided
      vision improved by -0.64 (SD 0.22) logMAR units in the ortho-k group, compared
      with -0.09 (SD 0.11) units in the control group. Variables which correlated with
      refractive change were corneal thickness, p-value of the nasal semi-meridian and
      the difference between central and peripheral corneal powers. A multiple factors
      model can account for 72% of the refractive change. CONCLUSIONS: Ortho-k using
      the OK-74 lens design achieved an average myopia reduction of 1.50 D. The model
      developed can provide an estimate of the refractive change likely to occur in
      ortho-k, a matter of importance to both clinician and patient.

PMID- 16303437
TI  - Orthokeratology in low myopia. Part 2: corneal topographic changes and safety
      over 100 days.
AB  - AIMS: Modern orthokeratology (ortho-k), using reverse geometry lens designs, is
      being widely used for myopia reduction world-wide but there has been no well
      controlled clinical trial of this procedure. This study reports on the associated
      corneal changes and short-term safety of an orthokeratology procedure using the
      OK-74 lens design (known as OK704 in the UK). METHODS: We carried out a 100-day,
      controlled, randomised clinical trial in which 14 subjects underwent ortho-k and
      a further 14 were fitted with alignment fit contact lenses. RESULTS: Central
      corneal flattening and peripheral corneal steepening occurred and myopia
      reduction was explained by the flattening of the central 2 mm of the cornea. The
      overall ocular health effects were similar in conventional and OK-74 lens wear.
      CONCLUSIONS: Corneal sphericalisation occurred. Daily wear of OK-74 lens and the
      conventionally-designed lens were equally safe over the 100-day period
      investigated. Further work is needed to evaluate the long term safety of ortho-k.

PMID- 16303438
TI  - The why and wherefore of soft lens visual performance.

PMID- 16303440
TI  - A review of rigid lens design.

PMID- 16303441
TI  - Six months of in-practice experience with a high Dk lotrafilcon a soft contact
      lens.
AB  - Recent innovations in research and development have brought two new high Dk soft
      contact lens materials to the market. The purpose of this study was to report the
      performance of one of these materials, lotrafilcon A, among a large and diverse
      number of patients and routine practices. Five hundred and forty seven patients
      were fitted with study lenses by 62 investigators in six countries and followed
      for 3-6 months of up to 30 nights extended wear. Clinical results showed good
      visual acuity, lens surfaces, biomicroscopy findings, and lens fit throughout the
      study. Patients rated the lens highly and were satisfied with the lens.
      Practitioners may expect good results among their patients who are appropriate
      candidates for this lens.

PMID- 16303442
TI  - Assessing the in vitro cell based ocular compatibility of contact lens materials.
AB  - A series of in vitro assays for determining the biocompatibility of ocular
      biomaterials have been developed and used to assess the differences in
      performance of omafilcon A, etafilcon A and nelfilcon A contact lens materials.
      The assays assessed bacterial attachment, macrophage adhesion, granulocyte
      adhesion and activation, epithelial cell adhesion and corneal cell contact
      damage. Overall, omafilcon A was found to be more biocompatible than the other
      materials although there was no significant difference between the epithelial
      cell adhesion and granulocyte adhesion and activation on any of the hydrogels.
      Etailcon A performed less well compared to nelfilcon A and omafilcon A with
      respect macrophage adhesion and bacterial adhesion. The results indicate that
      these biological assays can be successfully applied for the testing of contact
      lens materials and may be particularly useful in the in vitro screening of new
      extended wear contact lens materials where cell adhesion and activation may have
      a greater influence on clinical performance.

PMID- 16303443
TI  - Bandage soft contact lens barrier function: a clinical research note.
AB  - Corneal thickness pre- and post-operatively was measured on 18 volunteer subjects
      within the context of a clinical investigation of laser refractive surgery. All
      measurements were taken with regard for time of day, in order to counter any
      complicating diurnal influence on data accuracy. Of the 18 subjects, six lost or
      had accidently displaced their overnight bandage soft contact lenses the first
      night immediately after surgery, and 12 retained theirs. The individuals with
      lost bandage lenses exhibited uniformly thick, swollen corneas. In contrast, the
      other 12 subjects, with retained lenses, exhibited a stable corneal thickness
      map, displaying the characteristic relatively thick periphery that transitions to
      a thinner central region. Moreover, in the six affected subjects, application of
      a new overnight bandage lens resulted in recovery of the normal thickness pattern
      on day 2, as opposed to the uniform swelling or oedema of the previous day. In
      combination, these findings indicate a fluid barrier function on behalf of the
      bandage soft contact lenses, which allowed the corneal endothelial pump mechanism
      to counteract any extreme swelling or fluid accumulation. This previously
      unreported phenomenon helps explain the historical effectiveness of this
      treatment regimen for corneal bullous, or excessive fluid-retention, conditions.

PMID- 16303444
TI  - Videokeratoscopy in contact lens practice.
AB  - Videokeratoscopy is an important addition to contact lens practice, where a
      better understanding of corneal contour obviously helps the practitioner to
      achieve an optimal fitting relationship between the contact lens and the cornea.
      A variety of topographical maps, encompassing a large range of corneal
      conditions, are presented in this study to illustrate the different corneal
      contours the contact lens clinician is likely to encounter in practice.
      Interpretation of these corneal maps is outlined, with an emphasis on how one
      determines the appropriate contact lens fitting strategy based on the
      videokeratoscopic image.

PMID- 16303445
TI  - Proposed performance criteria for extended wear contact lenses.
AB  - The introduction of silicone-hydrogel materials has changed expectations for the
      response to contact lenses used in extended wear. In keeping with this technology
      shift, we have re-evaluated the criteria by which practitioners judge the
      performance of extended wear lenses. Attendees at the 1999 Annual Clinical
      Conference of the British Contact Lens Association were surveyed. The proportion
      of respondents who considered it appropriate to fit selected patients with
      conventional, disposable and silicone-hydrogel soft lenses for extended wear was
      63%, 67% and 86%, respectively. Only 11% of respondents did not fit extended wear
      because of personal experience with infectious keratitis, and over 50% relied on
      educators' advice in avoiding this practice. Fifteen per cent of practitioners
      reported fitting extended wear on occasions. Ninety-five per cent of respondents
      thought that the relative risk of infectious keratitis with daily wear compared
      with no lens wear should be ten or less, which was reduced to 60% when it was
      revealed that the current relative risk is estimated to be 60. A strong
      preference for a relative risk of infection with extended wear compared to daily
      wear of less than five times was indicated, which is consistent with current
      estimates. A minority of respondents were prepared to accept an overnight oedema
      level of over 6% with extended wear, although silicone-hydrogel materials have
      been shown to induce less than 4%. A wide variety of microcyst responses were
      considered reasonable, with many respondents accepting up to 40 per cornea;
      again, this result contrasted with early research data suggesting a level of 10
      microcysts or less occurring with silicone-hydrogel materials. Interpretation of
      these findings has led us to the following proposals for safe extended wear: (i)
      extended wear fitting should preferably be done with silicone-hydrogel materials,
      rather than conventional hydrogels, where the available parameter ranges overlap;
      (ii) the relative risk of corneal infection with extended wear compared to daily
      wear should be two to five times, providing the relative risk of daily wear
      compared to the no lens wear'situation is reduced to 20 times, and (iii) extended
      wear lenses should produce an average of no more than 4% overnight oedema and no
      more than 10 microcysts per eye in the long term.

PMID- 16303447
TI  - Corneal vascularisation: the superficial and the deep.

PMID- 16303448
TI  - Measuring non-spherical optical surfaces.
AB  - INTRODUCTION: More lens designs for the presbyopic market are emerging and the
      use of novel constructions to generate varifocal optics in contact lenses is
      increasing. A number of designs incorporate aspheric shapes, of known p-values on
      the front and back surface of contact lenses. Frequently, the back optic zone
      radius quoted by the manufacturer is a nominal reference making verification of
      these lenses difficult. The purpose of this study was to determine whether a
      videokeratoscope or an optical microspherometer could verify these complex
      surfaces. METHODS: Fifty-four concave test surfaces of known vertex curvatures
      (7.30 to 8.10 mm, in 0.1 mm steps) and known p-values (1.0 to 0.0, in 0.1 steps)
      were produced and measured with two different systems. RESULTS: The optical
      microspherometer was able to verify the vertex radius to a high degree of
      accuracy (+/- 0.072[2SD]) without bias (mean difference = 0.008 +/- 0.01(2SE]).
      However, verification of the p-value by utilising Baker's equation demonstrated a
      poor degree of accuracy (+/-0.574) and bias (mean difference=0.134, +/-0.078).
      The degree of accuracy for the measurement of the vertex radius of the concave
      surface, when using the videokeratoscope, was also very high (+/-0.09) but with a
      demonstration of bias (mean difference=-0.017, +/-0.012). The videokeratoscope
      was able to describe the p-value for the surface to a high degree of accuracy (+/
      0.136) but did demonstrate bias (-0.052, +/-0.018). These results for the
      measurement of the p-value for the optical microspherometry were statistically
      significantly different from that of the control measurement (p = 0.0379) and
      that for the videokeratoscope (p = 0.0042). CONCLUSION: To determine the degree
      of asphericity of a concave optical surface to an acceptable degree of accuracy a
      videokeratoscope can be used in preference to an optical microspherometer. Both
      instruments demonstrated a high degree of accuracy when measuring the vertex
      radius.

PMID- 16303449
TI  - Confocal microscopy of the normal human cornea.
AB  - The slit-scanning confocal microscope is a new clinical paradigm that allows the
      living human cornea to be viewed at a magnification of 680 x and a lateral
      resolution of 1 mum. As such, it allows corneal morphology to be inspected at a
      cellular level. The corneas of both eyes of 119 subjects who were evenly
      distributed in age from 10-80 years were examined using a Tomey ConfoScan P4 in
      vivo slit-scanning real-time confocal microscope (Erlangen, Germany). Good
      quality representative images of the various corneal layers were selected for
      detailed qualitative analysis and are displayed here. A grid of corneal layer
      versus age was constructed from these images; this tool can be used as a
      normative confocal microscopy reference against which suspected corneal
      abnormalities can be assessed.

PMID- 16303450
TI  - Process capability measurement of frequent replacement toric soft contact lenses.
AB  - PURPOSE: Frequent replacement soft contact lenses, and particularly toric soft
      lenses, require good reproducibility in order to avoid clinical problems arising
      from manufacturing variations in their parameters. This study assessed the actual
      and potential process capability of six frequent replacement toric soft lenses in
      relation to sphere power, cylinder power, cylinder axis, total diameter, back
      optic zone radius and centre thickness. METHOD: In total, 1260 lenses consisting
      of three sphere powers (plano, -3.00 and -6.00 D) were measured for six lens
      types. Three cylinder powers and six cylinder axes were assessed for each sphere
      power, except for one lens type where only two cylinder powers were available.
      RESULTS: Significant differences in reproducibility were found between the lens
      types tested. Process capability and optical quality decreased with increasing
      sphere power for all lenses. Cylinder power process capability tended to be
      better than that for sphere power. In general, lenses showed adequate
      reproducibility with those dimensions likely to affect lens fit, namely total
      diameter, back optic zone radius and centre thickness. CONCLUSIONS: Process
      capability was shown to be a useful measure of contact lens reproducibility for
      comparing toric soft lenses and assessing their potential for use on a frequent
      replacement basis. The results suggest some need for improvement in manufacturing
      accuracy and precision.

PMID- 16303451
TI  - An optometrist's personal perspective of aspects of refractive surgery.
AB  - The latter part of the last century has seen significant evolution in the area of
      refractive surgery, such that is has become a viable alternative to contact
      lenses, or spectacles, for an increasing number of patients. The developments of
      the principal techniques, in this ever-expanding field, are reviewed, and the
      increasing role of the optometrist in the pre-, intra- and post-operative
      management of the refractive surgery patient is described, based upon the
      author's personal experience within a non-profit, refractive surgery setting. In
      addition to highlighting pertinent features of the objective evaluation of
      patients, the importance of subjective assessment, pre- and postoperatively, is
      discussed, in terms of maximising post-surgery patient satisfaction. The scope
      for future research in this dynamic area is also considered.

PMID- 16303454
TI  - Key issues confronting the contact lens industry.

PMID- 16303452
TI  - Contemporary orthokeratology.
AB  - Orthokeratology is the temporary reduction or elimination of myopia and
      astigmatism with rigid contact lenses having a tetra-curve reverse geometry back
      surface design are currently utilised for this purpose. The essential features of
      this construction are described. Those clinical characteristics which are
      favourable, and those which are unfavourable, for the technique of
      orthokeratology are listed. Reverse geometry lenses can either be fitted
      empirically or by the use of diagnostic lenses. Videokeratoscopy is of value in
      identifying corneal distortion induced by problems such as poor centration.

PMID- 16303455
TI  - Flexure of thin rigid contact lenses.
AB  - The flexure of spherical rigid contact lenses was measured on the eyes of 10
      young subjects using a videokeratoscope. Five subjects had little or no with-the
      rule astigmatism (<0.75 D) andfive had moderate levels of with-the-rule
      astigmatism (1.00-2.00 D). Two lens materials (polymethylmethacrylate [PMMA] and
      Boston XO) in three centre thicknesses (0.05, 0.10 and 0.15 mm) were used in the
      study. No significant difference in the amount of flexure was found between the
      two materials tested. The degree of regular astigmatism on the lens front surface
      was found to increase as the centre thickness of the contact lens decreased. For
      the astigmatic group, the lenses with centre thicknesses of 0.05 mm had levels of
      front surface astigmatism similar to those of the underlying cornea. On spherical
      corneas the level of regular astigmatism can exceed that of the cornea for
      thinner lenses. When sphero-cylinder variations are accounted for, residual
      higher order aberration (root mean square) levels were found to approach those of
      the cornea when the lens thickness was reduced to 0.05 mm.

PMID- 16303456
TI  - A novel instrument to quantify the tension of upper and lower eyelids.
AB  - An instrument was developed for the objective measurement of passive lid tension
      of the upper and lower eyelid. Eyelid tension is defined as the first derivative
      of the force over elongation function. Lid tension was determined by gripping the
      eyelid at the eyelashes and displacing the lid while measuring the force exerted
      by the eyelid. Two motorised spindles provided motion control of the gripper in
      anterior/posterior and nasal/temporal directions. Each axis was fitted with a
      sensitive force transducer to record the force while stretching and relaxing the
      eyelid. Motion control, data collection and data analysis were computer
      controlled, with various user-selectable options for measurement speed, direction
      and end-of-measurement conditions. Calibration of the instrument reduced the
      maximum error of the recorded forces to +/- 10 mN. Repeatability for on-eye
      measurements was verified by multiple measurements on the same eye under
      identical conditions. Preliminary results from a pilot study, investigating
      differences between Asian and Caucasian lid tension showed no statistically
      significant difference between the two groups.

PMID- 16303457
TI  - Non-inflammatory corneal complications of contact lens wear.
AB  - Contact lenses can induce changes in the epithelium, stroma and endothelium of
      the cornea, all of which can be observed clinically using the slit-lamp
      biomicroscope. These complications include epithelial microcysts, vacuoles and
      staining, stromal oedema and vascularization, and endothelial polymegethism and
      blebs. Each complication can be attributed to one or more aetiological factors
      such as hypoxia, hypercapnia, tissue acidosis, trauma, hypersensitivity and
      toxicity. This review outlines the way in which these complications manifest
      clinically, and consideration is given to management strategies and likely
      prognoses. Early detection of these conditions and appropriate action can usually
      prevent more serious ocular complications.

PMID- 16303458
TI  - Amiodarone keratopathy and rigid contact lens wear.
AB  - Two cases are presented of patients wearing rigid gas permeable contact lenses
      who exhibited the typical fan-shaped patterns of corneal pigment deposition
      related to long-term medication containing amiodarone. The vortex corneal
      epitheliopathy and contact lens tolerance were monitored over several years. In
      both cases, the lens material was replaced with one incorporating an ultra-violet
      light inhibitor in view of the possibility of medically induced photosensitivity.

PMID- 16303460
TI  - On-eye dehydration of proclear, resolution 55G and acuvue contact lenses.
AB  - In order to compare the extent of dehydration of Proclear, Resolution 55G and
      Acuvue contact lenses overtime, 13 patients wore each lens during 4, 6 and 8 h.
      Three observers, initially shown to have a high inter-observer reliability,
      measured water content, with a soft contact lens refractometer before and after
      each period of wear. Absolute dehydration of Proclear and Resolution 55G lenses
      were similar after 4, 6 and 8 h of wear, but were smaller than for Acuvue lenses
      (1.2% compared to 5.7% after 8 h). The loss of lens mass following dehydration of
      Resolution 55G lenses, calculated with the change in lens relative water content
      was found to correlate very well with an in vitro study of the same material.
      Lens dehydration should be taken into account by clinicians when making their
      choice of soft contact lens.

PMID- 16303461
TI  - Comparative antimicrobial efficacy of multi-purpose hydrogel lens care solutions.
AB  - Ten single-bottle multipurpose hydrogel lens care solutions commercially
      available in the European market were evaluated for antimicrobial efficacy using
      the International Organization for Standardization's (ISO) Stand-Alone Procedure.
      The results of this study indicate that ReNu Multi Plus ReNu Multi Purpose,
      Complete and DUA meet the ISO Stand-Alone primary acceptance criteria for stand
      alone disinfectants against all challenge organisms: Staphylococcus aureus,
      Serratia marcescens, Pseudomonas aeruginosa, Candida albicans, and Fusarium
      solani. Solo-Care Soft, All-In-One Light, Optiplus, Opti Free Express, UniCare
      and Combi Comfort do not meet the ISO Stand-Alone primary acceptance criteria for
      one or more test organisms within their respective labelled minimum disinfection
      times. In addition, although not a requirement of the guidance document, only
      ReNu MultiPlus and ReNu Multi-Purpose exceeded the minimum ISO Stand Alone
      primary acceptance criteria within 25% (1 h) of their labelled minimum
      disinfection time for all test organisms. This evaluation provides a direct
      comparison of antimicrobial activity for commercially available multipurpose lens
      care solutions at their labelled minimum disinfection times. The results of this
      study should be considered when selecting appropriate lens care systems for
      patients.

PMID- 16303462
TI  - Clinical performance of polynomial lenses versus tri-curve lenses. I: initial
      comfort.
AB  - Twenty-two subjects were asked to wear custom-made polynomial back surface design
      rigid gas permeable (RGP) lenses and conventional tri-curve RGP lenses to compare
      the initial comfort provided by the two lens designs monocularly and binocularly.
      Polynomial lenses, based on tri-curve lens fittings, did not provide better
      initial comfort than tri-curve lenses. The results seem to indicate that an
      aspheric back surface alone may not play a very important role in the initial
      comfort of RGP lens wear. The method used to derive the specifications of the
      polynomial surface may, however, need further modifications to improve its
      accuracy.

PMID- 16303463
TI  - Clinical performance of polynomial lenses versus tri-curve lenses. II: ocular
      responses.
AB  - This study, which was a continuation of the previous one, aimed to determine the
      subjective and objective responses after wearing polynomial and tri-curve rigid
      gas permeable (RGP) lenses over a period of 6 months. Subjects were divided into
      two groups, each of which wore either one of these lens designs and 17 of 22
      subjects completed the 6-month study. Subjective responses were assessed by a
      questionnaire while the objective responses including vision, contrast
      sensitivity, lens fitting and the corneal integrity, corneal thickness and
      endothelial cell morphology were assessed by the examiner. There were no
      significant differences in the subjective ratings, vision, contrast sensitivity
      and the lens fitting between the two groups. Except for the p-value (p) and the
      apical radius (r(o)) along the steepest meridian and the coefficient of variation
      in cell size in the inferior corneal endothelium, there were no significant
      changes in the palpebral aperture size, the p-value and r(o) along the flattest
      meridian, corneal thickness and the other endothelial cell variables after the 6
      month study period. The poor success and high dropout rates of RGP lens wear in
      this study stress the importance and need for further investigations of such
      lenses.

PMID- 16303464
TI  - Effects of contact lens wear on corneal ultrastructure.
AB  - Over the past 30 years, a number of studies employing the techniques of light and
      electron microscopy have been conducted on the corneas of human and animal eyes
      in an effort to more fully understand the histopathological basis of clinically
      observed contact lens-related phenomena. This paper reviews studies that have
      sought to explain such effects, including epithelial abrasion, punctate staining
      and thinning; stromal oedema and thinning, and endothelial polymegethism. It is
      demonstrated that an understanding of contact lens-induced changes to corneal
      ultrastructure can have a significant impact on the clinical appreciation of the
      severity or otherwise of various conditions as observed with the slit-lamp
      biomicroscope.

PMID- 16303465
TI  - Topographical mapping and in-office modification in the management of an
      orthokeratology patient.
AB  - A 20-year-old female was fitted with rigid gas permeable (RGP) orthokeratology
      (ortho-k) lenses for overnight wear. Both lenses decentred nasally due to the
      tight fit of the alignment zone (AZ) and the peripheral zone (PZ). The AZ and PZ
      of both lenses were flattened using an in-office modification unit. Centration of
      the right lens improved but a small central island was also observed. The left
      lens still decentred nasally. Both findings indicated that the AZ and PZ of the
      right lens were too steep leading to 'lens vaulting' or excessive central
      clearance and inadequate tear exchange, respectively. The AZ and PZ of both
      lenses were flattened further using the modification unit and after the
      adjustment, both lenses centred well and the central island in the right eye was
      eliminated. This case demonstrates the usefulness of topographical corneal
      mapping and in-office modification of lenses in the management of ortho-k
      patients.

PMID- 16303466
TI  - Five years after dispensing--are contact lenses a success?

PMID- 16303468
TI  - 2001: a contact lens (space) odyssey.

PMID- 16303469
TI  - Lens prism in RGP manufacturing and its effect on edge quality.
AB  - Unwanted prism in lathe cut RGP lenses is most frequently caused by misalignment
      when re-blocking the button for cutting the front surface. The geometrical
      relationships in three types of alignment errors and the resulting variations in
      edge thickness were mathematically analysed and experimentally confirmed. The
      edge thickness variations in a prismatic lens along the circumference follow a
      cosine function. For a typical tri-curve lens design, an eccentric offset 30
      microm between the front and the back surface can lead to a difference in edge
      thickness of more than 50 microm Edge thickness variations are greatest for high
      power minus lenses with prominent lenticulation. The polished edge shape is
      significantly compromised by inconsistent edge thickness. Typically, the thinner
      side has a sharp and pointed edge, while the thicker side is blunt.

PMID- 16303470
TI  - Vision of low astigmats through thick and thin lathe-cut soft contact lenses.
AB  - Distance and near visual acuity of 13 low astigmats were determined in a double
      masked experiment through thick and thin (centre thickness 0.12 mm and 0.06 mm,
      respectively) spherical lathe-cut soft lenses. For each lens type, distance and
      near LogMAR VA and over-refraction were assessed with different logMAR VA charts.
      For 70% of the subjects, the residual astigmatism was significantly lower than
      the refractive astigmatism with thicker lenses. No statistically significant
      differences in the distance and near logMAR VA was found between the two lens
      types using any of the charts used, though, in general, logMAR VA obtained
      through the thicker lens was better than logMAR VA through the thinner lens. The
      variabilities in distance and near logMAR VA between the two lens types increased
      with decreased contrast. The variabilities in distance logMAR VA were greater
      with Chinese charts than with English charts, and LogMAR VA with Chinese charts
      were significantly worse for both lens types. Based on the results of this study,
      we concluded that thicker spherical lathe-cut soft lenses provide better vision
      in low astigmats. The Snellen acuity test is inadequate for vision assessment of
      soft contact lens wearers. When a patient wearing thin soft contact lenses
      complains of poor vision in spite of 6/6 or 6/5 Snellen acuity, changing to
      thicker lenses may be considered.

PMID- 16303471
TI  - Acute rigid gas permeable contact lens intolerance.
AB  - Rigid gas permeable (RGP) and polymethylmethacrylate (PMMA) lens wearers
      occasionally report episodes of acute intolerance which is experienced upon lens
      insertion. In this paper, we report two cases of such intolerance in which the
      probable cause was contact lens inversion. We also present the results of a study
      in which a custom-built calibrated strain gauge was used to measure the force in
      Newtons (N), required to invert RGP lenses [oxygen permeability, or Dk, values
      between 30 and 90 x 10(-11) (cm2/s) (mlO2/ml x mmHg)] and PMMA lenses of
      different spherical back vertex powers (+/-3.00 D, 9.00 D). Significantly, less
      force was required to invert minus powered lenses (17.5 +/- 4.8 N) than plus
      powered lenses (31.7 +/- 7 .4 N), irrespective of the material. PMMA lenses
      required more force to induce inversion than that required to invert RGP lenses.
      Lenses with a Dk of 90 required only two thirds of the force (20.0 +/- 5.8 N)
      required to cause inversion compared to PMMA lenses (32.9 +/- 11.0 N). High
      powered PMMA lenses were found to be more likely to fracture on inversion than
      any other lenses tested. The force required to return negatively powered lenses
      to their original shape, once inverted, was less than 25% of that initially
      required to induce inversion. Plus powered lenses either reverted to their
      original form spontaneously, or required less than 3% of the original inversion
      force to do so. It was concluded that practitioners should consider inversion as
      a possible reason for otherwise unexplained, acute RGP contact lens intolerance
      experienced upon lens insertion. The reason why inversion has eluded so many, as
      a possible cause of intolerance, is likely to be because minimal force is
      required to return those lenses, which do not crack or fracture, to their
      original shape.

PMID- 16303472
TI  - Developments in corneal topographic analysis following contact lens wear and
      refractive surgery.
AB  - There is now a wide range of devices available for corneal topographic analysis.
      Although most devices use the Placido disk approach, fluorescein profilometry,
      laser holography and scanning slit technology have also been employed. The colour
      coded topographical maps have been designed for ease of clinical interpretation.
      The application of this technology to further our understanding of the effects of
      contact lens wear and various forms of refractive surgery is demonstrated.
      Current developments include the merging of corneal topographic analysis and
      ocular wavefront sensing technology to create the capability of etching
      sophisticated corneal shapes in the course of refractive surgery so as to provide
      optimal aberration control.

PMID- 16303473
TI  - Contact lens-associated chemical burn.
AB  - We present the case of a young man who presented as an ophthalmic casualty after
      inserting a pair of bizarre-effect cosmetic hydrogel contact lenses while in a
      night-club. He failed to follow the manufacturer's guidelines and inserted the
      lenses before neutralising the storage solution. On presentation he was found to
      have bilateral corneal epithelial defects which required hospital treatment for 4
      days. He appears to have suffered no long-term sequelae.

PMID- 16303475
TI  - Risk factors for contact lens associated microbial keratitis.
AB  - Although the risk of developing contact lens associated microbial keratitis is
      small, the potential consequences of this condition, such as vision loss, are
      serious. This paper presents an analysis of the risk factors that have been
      identified for contact lens induced microbial keratitis, which include extended
      wear, hypoxia, non-compliance, blepharitis, diabetes mellitus, epithelial trauma,
      steroid use, therapeutic lens use, tobacco use, and possibly travel to warm
      climates. By remaining mindful of these risk factors, practitioners can take
      action and offer advice to patients so as to optimize the safety of contact lens
      wear.

PMID- 16303476
TI  - Corneal epithelial homeostasis following daily and overnight contact lens wear.
AB  - This report reviews and integrates our recent clinical and laboratory findings of
      the effects of daily (DW)/overnight (EW) contact lens wear on corneal epithelial
      homeostasis. In a prospective, double-masked human clinical study, three lens
      types (high and hyper Dk/t soft; hyper Dk/t RGP) were used to assess the effects
      of daily and overnight lens wear on corneal epithelial thickness, cell surface
      size, Pseudomonas aeruginosa (PA) binding to exfoliated epithelial cells and
      exfoliation rates. Concomitantly, we studied in a rabbit model, the effects of
      overnight lens wear on corneal epithelial surface cell viability (live/dead
      assay, TUNEL-labeling, Annexin-V staining, Bcl-2 expression), basal cell
      proliferation and migration patterns. The comprehensive results obtained yield
      important new insights on both the normal homeostasis of the corneal epithelium
      and the biological changes induced by contact lens wear.

PMID- 16303478
TI  - The tear (lacrimal) meniscus height in human eyes: a useful clinical measure or
      an unusable variable sign?
AB  - PURPOSE: To review notes and reports in the literature on assessments of human
      tear meniscus height (TMH) with the view to defining what the current state of
      knowledge is, and allow comparisons with data obtained on elderly individuals.
      METHODS: TMH data was obtained from 97 elderly individuals without significant
      eye disease. Photo-slit-lamp views, perpendicular to the lower marginal tear
      strip, were used to obtain close-up images by videography over approximately 30s.
      Repeated measures at the same location separated by a few seconds (time-dependent
      TMH measures, tTMH), or repeated measures along the length of the middle portion
      of the lower eyelid (position-dependent TMH measures, pTMH) were made. The
      results were compared to those from published reports of TMH. RESULTS: For
      elderly individuals, tTMH averaged 0.185+/-0.088 mm, while pTMH averaged 0.189+/
      0.093 mm. The distribution of TMH measures however included a number of data sets
      with a much higher average, and which could be separated from the main group of
      data using cluster analyses approach (> 0.23 mm, P < 0.001). Literature-reported
      values for TMH, assessed by a perpendicular view, average 0.215 mm (range of
      average values from 0.163 to 0.350 mm), whereas those made from a tangential view
      average 0.343 mm (range 0.215-0.460 mm). CONCLUSIONS: The average TMH value of
      close to 0.2mm in the elderly, as compared to the small number of individuals
      with rather greater TMH values of up to 0.7 mm, might therefore be considered as
      indicative of their having normal tear volume, with a few individuals having
      reflex tearing. Based on the data and literature values, a lower cut-off limit
      for normal would be </=0.1 mm, while >/=0.25 mm would indicate reflex tearing
      and/or sub-optimal tear drainage. An alternative interpretation is that elderly
      individuals have a subnormal tear film volume, with just a few individuals having
      adequate tear volume. Further work is clearly needed to resolve this issue.

PMID- 16303479
TI  - Recovery of the visual acuity in a family with Reis-Buckler dystrophy.
AB  - BACKGROUND: The hereditary Reis-Buckler dystrophy is one of the anterior
      localised corneal dystrophies with superficial reticulated opacities, sometimes
      in combination with recurrent attacks of corneal erosion. Phototherapeutic
      keratectomy (PTK) is now the first method to consider for managing this disease
      when intervention is required. METHODS: We treated six eyes of four related
      patients with Reis-Buckler dystrophy, who had a demonstrable reduction in visual
      acuity due to corneal opacities within their virgin corneas (three eyes),
      penetrating (one eye) or lamellar (two eyes) grafts. We present the results of
      change in visual acuity and best corrected spherical spectacle and contact lens
      refraction at 1 year following surgery. In one case, we had to fit a rigid
      contact lens to correct the hyperopic shift which caused anisometropia. RESULTS:
      The mean spherical refractive change 1 year after PTK surgery was 0.33+/-S.D.,
      1.8D. A hyperopic shift was observed in four eyes. Visual acuity remained stable
      in all patients 1 year after surgery. The central corneal area remained clear,
      and mean best spectacle corrected visual acuity improved from +0.8 logMAR before
      PTK to +0.15 logMAR after 1 year. There was no significant change (P>0.8) between
      the mean 1 year best spectacle corrected visual acuity (+0.125 log MAR +/- S.D.
      0.15) and the best contact lens corrected visual acuity (+0.108 log MAR +/- S.D.
      0.16). After fitting a contact lens in one patient to correct anisometropia, the
      hyperopic shift did not change significantly during 12 months of follow-up. It
      was not necessary to adjust the lens parameters. One patient required cataract
      surgery. CONCLUSION: PTK corneal surgery is the treatment of first choice when
      intervention is required in patients with Reis-Buckler dystrophy because it is
      safe and much less invasive than lamellar or penetrating keratoplasty. Contact
      lens fitting following PTK has not changed corneal shape.

PMID- 16303480
TI  - The application of counter immunoelectrophoresis (CIE) in ocular protein studies.
      Part I: time dependent deposition patterns of immunoregulatory proteins on
      anionic hydrogel contact lenses.
AB  - This paper focuses on the effects of wear regime on the deposition pattern of
      important immunoregulatory proteins on FDA Group IV etafilcon-A lenses.
      Specifically, the aim was to assess the extent to which the daily disposable wear
      modality produces a different deposition of proteins from the conventional daily
      wear regime which is coupled with cleaning and disinfection. Counter
      immunoelectrophoresis (CIE) was employed to detect individual proteins in lens
      extracts from individual patients and focused on the analysis of five proteins,
      IgA, IgG, lactoferrin, albumin and kininogen. Deposition was monitored as a
      function of time; significantly lower deposition was detected on the daily
      disposable lenses.

PMID- 16303482
TI  - Central thickness of hydrogel contact lenses as a predictor of success when
      fitting patients with tear deficiency.
AB  - A randomized, double masked, study was designed in order to investigate the
      relationship between the central thickness of hydrogel contact lenses and the
      overall comfort of patients with tear deficiency. To allow for statistical
      analysis, a thin lens was fitted in one eye and a thicker lens of the same
      characteristics in the contralateral eye. Subjects were asked to wear the lenses
      for 30 days on a normal daily wear basis and to graduate several factors such as
      comfort, dryness sensation, redness, photophobia, tearing, quality of vision and
      others. The results indicate that thicker lenses were preferred in terms of
      comfort, dryness sensation, photophobia and handling whereas thinner lenses were
      considered to give a better quality of vision. As a whole, thicker lenses were
      better tolerated by the patient. Central thickness was found to be of significant
      relevance when choosing a contact lens, especially when the tear film is
      deficient.

PMID- 16303481
TI  - The application of counter immunoelectrophoresis (CIE) in ocular protein studies
      Part II: Kinin activity in the lens wearing eye.
AB  - The kinin family are a group of bioactive peptides that are closely involved in
      the modulation of vascular inflammation and local injury. We have demonstrated
      here, for the first time, a link between kinin activity and contact lens wear.
      Protein extracts from daily and extended wear etafilcon A, Group IV, Acuvue
      lenses (Vistakon), were analysed by counter immunoelectrophoresis. In this way,
      kinin activity associated with contact lens wear was detected. High molecular
      weight kininogen was used as the marker protein. In contrast, no kinin activity
      was detected in the non-lens wearing normal eye.

PMID- 16303483
TI  - Optimising RGP lens fitting in normal eyes using 3D topographic data.
AB  - PURPOSE: To analyse, retrospectively, the effect of fitting characteristics on
      comfort of wear and the role that 3D topographic data can play in attaining an
      optimal lens fit with rigid gas permeable (RGP) contact lenses in normal eyes.
      METHODS: Included were 60 normal myopic eyes (1.00-5.00 D) with astigmatism
      limited to 2.00 D. Lenses were ordered empirically, based on traditional fitting
      rules. RESULTS: The initial fit based on traditional computation was accepted in
      40% of the eyes. To achieve an acceptable fit, 15% of the eyes needed an
      adaptation of the back optic zone radius, in 28% switching from a multicurve to
      an aspheric lens design was indicated and in 17% a non-rotational symmetric lens
      design was favoured. The reason for changing the lens parameters could in 88% be
      attributed to mid-peripheral differences between corneal shape as found with 3D
      corneal topography. Average comfort of wear improved statistically significantly
      (chi(2), P<0.05) from 5.2 initially to 7.7 after 3 months in the group with
      optimal lens fits, while comfort slightly decreased (not significant) in the
      group with sub-optimal fits. Switching to a non-rotational symmetric lens design,
      when indicated, improved comfort significantly (chi(2), P<0.05) from 5.0 to 7.3.
      CONCLUSION: In normal eyes, the measurement of corneal shape, especially in the
      mid-peripheral regions, is of importance to optimise RGP lens fit. Optimised lens
      fits increases comfort of wear.

PMID- 16303485
TI  - The risk of transmission of variant Creutzfeldt-Jakob disease via contact lenses
      and ophthalmic devices.
AB  - This review collated the available information regarding the risk of transmission
      of variant Creutzfeldt-Jakob disease (vCJD) via contact lenses and other
      ophthalmic devices. The topics examined include: the emerging background science
      of the unconventional infective agent, the prion, particularly those factors
      affecting transmission; the estimates of the number of undiagnosed infective
      individuals; and evidence of infectivity in the external eye. Despite many
      uncertainties in the literature, we conclude that cross-infection is
      theoretically possible. An assessment of the extensive search for a complete
      inactivation procedure resulted in the recommendation of the use of sodium
      hypochlorite (NaOCl), which does not appear to distort rigid lenses. Further
      tests are required for other devices.

PMID- 16303486
TI  - Adverse events with silicone hydrogel continuous wear.
AB  - High Dk silicone hydrogel lenses have overcome many of the hypoxic problems
      associated with traditional extended wear and the popularity of continuous wear
      (up to 30 nights) with these lens types is increasing. Results from clinical
      trials indicate that the typical physiological changes associated with edema from
      conventional extended wear of low Dk/t lenses do not occur with continuous wear
      of silicone hydrogel lenses. These changes include neovascularization, striae,
      microcysts and an increase in bulbar and limbal hyperemia. It is perhaps not
      surprising though that a number of adverse events do still occur with silicone
      hydrogel lenses when they are worn on a continuous wear basis. These include
      inflammatory conditions such as contact lens-induced peripheral ulcers (CLPU),
      contact lens-induced acute red eye (CLARE), infiltrative keratitis (IK) and
      contact lens papillary conjunctivitis (CLPC). Other events such as superior
      epithelial arcuate lesions (SEAL) and localised CLPC may be due to mechanical
      influences. While these conditions are not sight threatening, they may be painful
      and are certainly inconvenient to both the patient and the practitioner. It is
      therefore very important that the signs and symptoms associated with these events
      be recognised in order that they may be accurately identified and appropriately
      managed. The purpose of this review article is to describe the pathophysiology,
      etiology, and clinical presentation of these adverse events when observed with
      continuous wear contact lenses and to discuss their associated risk factors and
      incidence. Clear management and treatment strategies are also presented and a
      number of approaches to minimize adverse events with continuous wear of silicone
      hydrogel contact lenses are suggested.

PMID- 16303487
TI  - In vitro evaluation of the dehydration characteristics of silicone hydrogel and
      conventional hydrogel contact lens materials.
AB  - PURPOSE: This study investigated the in vitro dehydration performance of silicone
      hydrogel and conventional hydrogel contact lens materials. METHODS: In vitro
      dehydration was assessed using a gravimetric method. The mass loss over time of
      Focus Night&Day, PureVision, Optima, Acuvue and Proclear Compatibles was measured
      as the ambient temperature increased from room temperature to 34 degrees C under
      varying airflow and humidity conditions. RESULTS: Dehydration data demonstrated a
      typical ogival form. The results were best fitted with a double exponential, non
      linear regression model, which accounted for at least 99% of the variance.
      Regardless of material, increased airflow had a greater impact on dehydration
      rate than increased humidity (P<0.05). Relative dehydration amounts were strongly
      correlated with initial water content (r(2)=0.92), with higher water content
      materials dehydrating to a greater extent. CONCLUSIONS: In vitro dehydration
      studies of conventional and novel silicone-containing hydrogel materials
      indicated that evaporation rates from materials are predominantly water content
      related, with only subtle differences between materials of similar water contents
      being seen. Environmental conditions have a significant impact on in vitro
      dehydration, with increased airflow having a greater impact than reduced humidity
      on increasing dehydration rates. In vitro dehydration is closely related to bulk
      water diffusion rates and, as a result of their low water content, silicone
      containing hydrogel materials exhibit low levels of dehydration compared with
      high water content hydrogel contact lens materials. Further, in vivo studies are
      necessary to see if the in vitro dehydration behaviour of silicone hydrogel
      materials is predictive of in-eye performance.

PMID- 16303489
TI  - Soft bifocal contact lenses: the limits of performance.

PMID- 16303491
TI  - Subjective and objective measures of corneal staining related to multipurpose
      care systems.
AB  - An objective, digital-imaging method of measuring corneal staining was evaluated
      in 24 subjects wearing soft contact lenses. The method was used to compare the
      clinical performance of common multipurpose care systems (MPS) for soft contact
      lens care. Subjects used three different MPS, one containing polyquaternium-1
      (PQ) and two containing polyhexanide (PX1 and PX2), for 2 weeks in a randomised,
      single-masked (investigator) crossover study. Corneal staining induced with the
      three MPS was analysed using an image-processing program (ImageTool, UTHSCSA
      Version 2, University of Texas, USA). Conjunctival hyperaemia and papillae were
      also evaluated. The intraclass correlation coefficient was similar with image
      analysis to that of investigator grading (0.876, 0.879, respectively).
      Significant differences in staining response were detected using the objective
      method. There was significantly less staining area with polyquaternium-1 (PQ)
      than polyhexanide (PQ: 0.12 mm(2), PX2: 0.91 mm(2)). Inferior palpebral papillae
      were significantly greater with PX2 than with PQ (1.0, 0.7 (0-4), respectively).
      The technique was shown to be an effective method of evaluating different corneal
      staining responses. Bilateral corneal staining in three or more quadrants is
      useful in the diagnosis of MPS-related staining.

PMID- 16303492
TI  - Soft contact lens extended wear affects corneal epithelial permeability: hypoxic
      or mechanical etiology?
AB  - Contact lens extended wear increases the permeability of epithelium to sodium
      fluorescein (P(dc)). The exact mechanism is not known. However, changes in P(dc)
      likely result from either corneal hypoxia or mechanical trauma, or both. We
      explored the effects of one-night continuous wear with either high- or low-Dk/t
      soft lenses on P(dc). The results show that corneal epithelial barrier function
      decreases significantly with both lens groups. We also observed that Asian eyes
      had higher P(dc) after overnight wear compared to non-Asian and that for both
      Asian and non-Asian eyes, the elimination of corneal hypoxia did not prevent
      changes in epithelial permeability.

PMID- 16303493
TI  - Anatomy of a regimen: consideration of multipurpose solutions during non
      compliant use.
AB  - Consumers are often non-compliant with instructions for contact lens care
      products. This study explores the antimicrobial capacity of multipurpose
      solutions using variable use conditions. Opti-Free Express (Alcon) Multi-Purpose
      Disinfecting Solution with Polyquad (Alcon) and Aldox (Alcon) antimicrobial
      system and products containing PHMB (ReNu MultiPlus, Solo-care, and Complete
      multipurpose solutions) were evaluated. Products were challenged with Fusarium
      solani, Candida albicans, Serratia marcescens, Pseudomonas aeruginosa, and
      Staphylococcus aureus. The antimicrobial activity and effectiveness of regimen
      steps, rinse volume, stored lenses and organic soil were evaluated. The results
      show that products using similar regimens can show different disinfection
      abilities. Opti-Free Express Multi-Purpose Disinfecting Solution retained
      effectiveness using variable and non-compliant conditions.

PMID- 16303494
TI  - Clinical monitoring of ocular physiology using digital image analysis.
AB  - AIM: To examine the use of image analysis to quantify changes in ocular
      physiology. METHOD: A purpose designed computer program was written to
      objectively quantify bulbar hyperaemia, tarsal redness, corneal staining and
      tarsal staining. Thresholding, colour extraction and edge detection paradigms
      were investigated. The repeatability (stability) of each technique to changes in
      image luminance was assessed. A clinical pictorial grading scale was analysed to
      examine the repeatability and validity of the chosen image analysis technique.
      RESULTS: Edge detection using a 3 x 3 kernel was found to be the most stable to
      changes in image luminance (2.6% over a +60 to -90% luminance range) and
      correlated well with the CCLRU scale images of bulbar hyperaemia (r=0.96),
      corneal staining (r=0.85) and the staining of palpebral roughness (r=0.96).
      Extraction of the red colour plane demonstrated the best correlation-sensitivity
      combination for palpebral hyperaemia (r=0.96). Repeatability variability was
      <0.5%. CONCLUSIONS: Digital imaging, in conjunction with computerised image
      analysis, allows objective, clinically valid and repeatable quantification of
      ocular features. It offers the possibility of improved diagnosis and monitoring
      of changes in ocular physiology in clinical practice.

PMID- 16303495
TI  - Contact lens wearer profile 2002.

PMID- 16303496
TI  - Environmental impact of three replacement modalities of soft contact lens wear.
AB  - PURPOSE: To illustrate the environmental impact of three contact lens replacement
      modalities, and to place this into a broader environmental context. METHODS:
      Environmental impact was calculated by sorting the packaging used in the supply
      of three representative contact lens systems into their constituent materials
      (liquid, plastic, paper, metal and glass), determining their mass, calculating
      the annualised consumption by a typical contact lens wearer, and factoring the
      data against published indices of the environmental impact of the constituent
      materials. RESULTS: Conventional lens wear had the highest impact and planned
      replacement lens wear (monthly disposable) had the lowest impact. CONCLUSIONS:
      The overall environmental impact of waste generated thorough the use of contact
      lens products by the end consumer is insignificant (0.5%) compared with the
      amount of waste generated in our everyday life.

PMID- 16303497
TI  - A test routine in order to minimise an artefact in tear meniscus height
      measurement.

PMID- 16303500
TI  - Hypersensitivity responses and contact lens wear.
AB  - Hypersensitivity diseases that involve the eye are common reasons why patients
      present to eyecare practitioners. Common ocular hypersensitivity disorders
      include allergic conjunctivitis, giant or contact lens induced papillary
      conjunctivitis and atopic keratoconjunctivitis. The diagnosis and management of
      ocular hypersensitivity can present a challenge to eyecare practitioners and an
      understanding of the mechanisms that underlie the signs and symptoms of such
      conditions is necessary for their appropriate management. This article reviews
      the mechanisms by which the eye responds to antigenic challenges, the
      pathogenesis of ocular hypersensitivity responses, particularly in relation to
      contact lens wear, and illustrates possible management strategies.

PMID- 16303501
TI  - The limbal vasculature.
AB  - The cornea is an avascular structure whose closest point of approach to the
      systemic blood stream is provided by the limbal vessels. Activity within these
      structures provides the clinician with a sensitive indicator of contact lens
      performance and associated problems. In this paper, the anatomy and physiology of
      the limbal vessels is reviewed with particular attention to the control of
      capillary perfusion. Mechanisms whereby soft contact lenses can interact with
      this network of vessels are considered.

PMID- 16303502
TI  - A keratoconus fitting system using the axial profile to establish optimum lens
      parameters.
AB  - This paper describes the application of a fitting system for keratoconus defined
      according to the integrated configuration of the optic and periphery, referred to
      as the axial profile. Incremental steps are arithmetic for a given total diameter
      across the range necessary for keratoconus and increased or decreased by varying
      the back optic zone radius (BOZR) and the axial edge lift (AEL) in combination,
      or by retaining a constant BOZR and reducing the AEL. An introductory section
      discusses selection of initial rigid trial corneal contact lenses for keratoconus
      and arrival at an optimum end point to the fitting process.

PMID- 16303503
TI  - An evaluation of 1-day disposable contact lens wear in a population of allergy
      sufferers.
AB  - PURPOSE: This was a multi-site, 128-subject, bilateral crossover study to
      evaluate subjective comfort and slit-lamp findings with 1-day disposable contact
      lenses in a population of allergy sufferers during periods when allergen levels
      were elevated. METHODS: The study involved 1-month of single-use daily wear with
      a 1-day disposable test lens (1. DAY ACUVUE Brand Contact Lenses, Johnson &
      Johnson Vision Care) and 1-month of daily wear with subjects' habitual lenses
      replaced to their usual replacement schedule. Pollen and mould counts were
      obtained for each site 1 week prior to the study and twice weekly throughout the
      study period. Subjective comfort and slit-lamp findings were recorded at baseline
      and after 1-month's wear of each modality. RESULTS: Sixty-seven percent of
      subjects agreed that the 1-day disposable lenses provided improved comfort when
      compared to the lenses they wore prior to the study, compared with 18% agreeing
      that the new pair of habitual lenses provided improved comfort. The 1-day
      disposable lenses showed greater improvement in slit-lamp findings from baseline
      than new habitual lenses. CONCLUSION: The use of 1-day disposable lenses is an
      effective strategy for managing allergy-suffering contact lens wearers.

PMID- 16303504
TI  - A review of entropion and its management.
AB  - This article reviews the various types of entropion: congenital, spastic,
      involutional, and cicatricial. Entropion diagnosis and clinical evaluation is
      discussed. Management from non-surgical to surgical procedures is reviewed.

PMID- 16303507
TI  - A physiological perspective on the swelling properties of the mammalian corneal
      stroma.
AB  - PURPOSE: The present studies were designed to assess whether measurement of
      corneal stroma swelling in the laboratory, especially in non-physiological
      solutions, was associated with a measurable effect on the keratocytes. METHODS:
      Complete corneal stroma preparations were made from quality- and age-selected
      recent post-mortem cattle eyes. These were either assessed immediately or
      incubated in three different solutions, namely a balanced salts solution with
      glucose (BSSG), isotonic phosphate buffered saline (PBS) or pure water.
      Incubations were carried out at 37 degrees C for 9h, and repeated measures of wet
      mass made so that the rates and extent of swelling could be determined. After
      incubation, an aqueous extract was made of the stroma for measurements of the
      levels the enzymes lactate dehydrogenase (LDH), aldehyde dehydrogenase (ALDH) and
      N-acetyl-beta-glucosaminidase. RESULTS: The initial rates of swelling were lowest
      in BSSG, marginally faster in PBS and much faster in water. The secondary rates
      of swelling showed the same sequence being 10.0%/h in BSSG, 14.8%/h in PBS and
      34.2%/h in water. Compared to non-incubated preparations, reductions in all three
      enzyme activities occurred. For LDH, these were 15% with BSSG, 40% in PBS and 80%
      with water. Similar results were seen with ALDH activity when comparing the three
      incubation solutions, while incubation in BSSG also resulted in a substantial
      (40%) reduction in N-acetyl-glucosaminidase activity. CONCLUSIONS: When immersed
      in an isotonic BSSG with added glucose at 37 degrees C, the swelling of a
      complete bovine corneal stroma is much less than smaller pieces of stroma, and
      also slightly less than if isotonic PBS was used. With the use of BSSG, little or
      no change in cytoplasmic enzyme activities occurred, but measurable decreases
      were noted with PBS and very substantial decreases when water was used,
      indicating a toxic effect on the keratocytes. The observation that substantial
      decreases in a lysosomal enzyme activity could occur even with the use of BSSG
      indicate substantial stress is imposed on the stroma during these types of
      experiments. Notwithstanding, the data collectively indicate that the keratocyte
      cells within the collagen matrix of the stroma can be substantially damaged and
      this needs to be taken into account in future experiments on the true physiology
      of the corneal stroma.

PMID- 16303508
TI  - Analysis of contact lens intolerance by exploring neuroanatomic integration of
      ocular surface defense.
AB  - This paper reviews the anatomic, neuronal and mechanical factors that affect
      contact lens wear, and outlines several areas where compromised ocular surface
      defense arising from dysfunctional neuroanatomic integration might be the source
      of or a contributor to contact lens intolerance. Suggestions for clinical work-up
      by analyzing neuroanatomic integration are presented as a logical way to dissect
      this complex problem.

PMID- 16303509
TI  - The cascade hypothesis of keratoconus.
AB  - Keratoconus, a non-inflammatory thinning of the cornea, is a leading indication
      for corneal transplantation. For its causation, we propose a "Cascade Hypothesis"
      stating that keratoconus corneas have abnormal or defective enzymes in the lipid
      peroxidation and/or nitric oxide pathways leading to oxidative damage. The
      accumulation of oxidative, cytotoxic by-products causes an alteration of various
      corneal proteins, triggering a cascade of events, (i.e. apoptosis, altered
      signaling pathways, increased enzyme activities, fibrosis). This hypothesis is
      supported by biochemical, immunohistochemical and molecular data presented in
      this review. Based upon this evidence, one can speculate that keratoconus
      patients should minimize their exposure to oxidative stress. Protective steps
      should include wearing ultraviolet (UV) protection (in the contact lenses and/or
      sunglasses), minimizing the mechanical trauma (eye rubbing, poorly fit contact
      lenses) and keeping eyes comfortable with artificial tears, non-steroidal anti
      inflammatory drugs and/or allergy medications.

PMID- 16303510
TI  - High- and low-contrast visual acuity measurements in spherical and aspheric soft
      contact lens wearers.
AB  - Visual reduction produced by spherical aberration is not always apparent with
      high-contrast optotypes, therefore, a measure of low-contrast visual acuity
      (LCVA) may be more revealing. In theory, by applying a series of curves to
      produce an aspheric surface, one should be able to reduce the defocus resulting
      from spherical aberration. This clinical investigation sought to evaluate high-
      and low-contrast visual acuity under natural conditions using the CooperVision
      Frequency 55 spherical and aspheric planned replacement soft contact lenses
      (CLs). The objective outcome showed no statistically significant difference
      between the spherical or aspheric design lenses for high- or low-contrast visual
      acuity. However, based on subjective outcomes, this study implies a 2:1
      preference for the aspheric design lens, suggesting the consideration of
      individual corneal topography and the importance of diagnostic lens fitting for
      patient satisfaction.

PMID- 16303511
TI  - Hydrogel contact lens-induced corneal warpage.
AB  - BACKGROUND: Although contact lens-induced corneal warpage is most frequently
      associated with PMMA lenses, approximately 27% of reported cases of corneal
      warpage have been attributed to hydrogel lens wear. The change in corneal contour
      may be the result of either mechanical deformation, chronic metabolic insult, or
      a combination of mechanical and metabolic challenges. Limited oxygen
      transmissibility through some hydrogel lenses may lead to chronic hypoxia and
      acidosis. These metabolic challenges can change corneal physiology sufficiently
      to cause clinically significant corneal warpage. CASE REPORTS: Three cases of
      hydrogel contact lens-induced corneal warpage are presented. In all three cases,
      cessation of lens wear led to restoration of the normal corneal contour and
      visual acuity. All patients were refit with more oxygen-permeable lenses, and
      have successfully resumed wearing contact lenses. CONCLUSION: Certain individuals
      who wear hydrogel contact lenses can experience corneal warpage. Clinical signs
      of corneal warpage include changes in refractive error, decreased visual acuity
      with spectacle correction, and changes in corneal topography. Serial topography
      is useful to monitor the cornea to resolution of the condition. Contact lenses
      with higher oxygen transmissibility will frequently alleviate the relative
      hypoxia that may be associated with corneal warpage.

PMID- 16303512
TI  - Management of neurotrophic keratopathy.
AB  - Neurotrophic keratopathy is an epithelial defect associated with fifth nerve
      damage, arising from numerous etiologies, which can be difficult to treat.
      Depending on the location of these defects, they can also prove to be sight
      threatening if treatment is unsuccessful. Several treatment options are available
      to assist in the resolution of these defects and, due to the serious potential
      consequences for sight if not well managed, all treatment options should be
      considered. This reporting of a patient that developed neurotrophic keratopathy
      after an intraocular surgical procedure includes details of the early, mid and
      late stages of the epithelial defect, the treatments that were instituted and the
      outcomes. The various treatments that are available for management of
      neurotrophic keratopathy and other persistent epithelial defects are discussed.

PMID- 16303514
TI  - Contact lens care in keratoconus.
AB  - PURPOSE: To quantify the complexity involved in fitting contact lenses on the
      eyes of patients with keratoconus. METHODS: The contact lens care of one randomly
      selected eye each of 38 keratoconus patients was retrospectively analyzed and
      compared to that of 38 gender and age matched controls. We evaluated the number
      of diagnostic contact lenses used to establish the initial contact lens order,
      number of ordered rigid gas permeable (RGP) contact lenses needed to complete the
      fit, number of office visits during the initial 4 months of care, best spectacle
      and RGP contact lenses corrected Log MAR visual acuities, complications
      encountered, and whether or not the patient was successful in contact lens wear.
      RESULTS: Keratoconic eyes statistically used more diagnostic lenses, more ordered
      lenses, and more office visits than did normal eyes. Visual acuities improved
      from an average of 20/40 with spectacles to an average of 20/20 by use of RGP
      contact lenses in keratoconic eyes. Visions were corrected to 20/20 with both
      spectacles and contact lenses in control eyes. Sixty nine percent (69%) of
      keratoconic eyes and 95% of controls were successful in contact lens wear.
      CONCLUSIONS: Contact lens care of keratoconic eyes is more challenging than care
      of normal eyes because of the need for more diagnostic and ordered contact lenses
      and the use of more professional time. Keratoconic eyes may suffer more
      complications than normals during contact lens care, but this does not affect the
      success rates, and such patients benefit from enhanced visual acuity with RGP
      contact lenses compared to that achieved with spectacles.

PMID- 16303515
TI  - Feasibility of contact lens fitting on keratoconus patients with INTACS inserts.
AB  - PURPOSE: To demonstrate the feasibility of contact lens fitting in keratoconus
      patients with INTACS inserts. METHODS: A chart review was conducted of all
      patients with bilateral keratoconus who were treated with INTACS inserts on one
      eye and who were subsequently referred for contact lens fitting in a university
      based contact lens practice between April 2000 and April 2002. The study was a
      retrospective, non-comparative case series. The uncorrected and best spectacle
      corrected visual acuity (BSCVA) after INTACS implantation surgery, postoperative
      best contact lens-corrected visual acuity (BCLVA), number of diagnostic contact
      lenses used, number of contact lenses ordered within a 4-month follow-up period,
      contact lens complications encountered, final base curves, final lens powers, and
      final wearing times were determined. RESULTS: Three keratoconic patients meeting
      the selection criteria were found through the chart review. Prior to surgery, all
      patients had uncorrected visual acuity (UCVA) of 2.0 logMAR (counting fingers).
      This improved to a mean of 0.81+/-0.25 logMAR (20/125-1) after surgery. Mean
      BSCVA also improved from 0.51+/-0.30 logMAR (20/60-2) to 0.30+/-0.16 logMAR
      (20/40). The mean postoperative best contact lens-corrected visual acuity was
      0.02+/-0.10 logMAR (20/20-1). The number of diagnostic lenses ranged from 1 to 7.
      The numbers of contact lenses ordered during the 4-month follow up period ranged
      from 1 to 3. Two eyes were fitted with larger than usual lens designs made of
      rigid gas-permeable material and one eye was fitted with a toric soft lens. The
      final lens power ranged from +1.25 to -21.0D with a mean spherical equivalent of 
      7.46+/-11.89 D. Final wearing times ranged from 2.5 to 12.0h. CONCLUSION: Fitting
      contact lenses on keratoconus patients who have INTACS inserts is feasible and
      has a role in augmenting their vision.

PMID- 16303516
TI  - Verification of the vertex powers of varifocal rigid contact lenses.
AB  - INTRODUCTION: Increasingly aspherical optics are used in contact lens designs to
      produce a varifocal effect to correct presbyopia. Whilst no current ISO standard
      describes a method to verify these products, the vertex power needs to be
      verified by the manufacturer and optometrist. Visionix claim that the VC2001
      instrument is able to resolve the vertex power of complex contact lenses and that
      it has been adopted by contact lens manufacturers as their "gold standard" method
      of measure. Practitioners rely on the focimeter for contact lens verification and
      accept that it has poorer resolution. This raises the question of whether
      practitioners can verify the vertex powers of varifocal contact lenses to a
      sufficient sensitivity. The purpose of this study is to determine whether a
      focimeter can differentiate between various vertex powers incorporating differing
      degrees of asphericity that are used in contact lens designs. METHODS: A range of
      varifocal contact lenses were used with single vision contact lenses as controls.
      Three types of focimeters were used: a manual focimeter, a projector focimeter
      and a computerised focimeter (standard and contact lens modes). The VC2001
      assessed the vertex powers over the optical zone and was used as a reference for
      the focimeters. The measures from the VC2001 and the focimeters were analysed by
      discrepancy analysis. RESULTS: All discrepancy measures fell outside two standard
      deviations for either the varifocal contact lenses or the single vision contact
      lenses when the focimeters were compared to the VC2001. This raises the issue of
      whether the focimeters are measuring the same parameter as the VC2001. Only the
      analysis of the repeated measurements from the manual focimeter for single vision
      contact lenses demonstrated an acceptable measure of precision (+/-0.21, 2S.D.)
      with a very small degree of bias (mean difference -0.024, +/-0.02 [2S.E.]).
      CONCLUSION: These results suggest that the manual focimeter can measure the
      vertex powers for single vision contact lenses to an acceptable degree of
      precision. The vertex powers of varifocal lenses cannot be verified using
      standard practice equipment. The VC2001 has poor precision for power measurements
      and may not be measuring the same parameter as the focimeters and therefore
      questions the validity of the VC2001 as the "gold standard" for vertex power
      measurement.

PMID- 16303517
TI  - Local oxygen transmissibility of disposable contact lenses.
AB  - AIM: Despite global standardisation in measurement of oxygen transmissibility
      (Dk/t), in our clinic we continue to see limbal vasculature changes in patients
      wearing some disposable lenses. The use of central Dk/t as a simple designator of
      a contact lens oxygen performance has clearly failed, it being acknowledged as
      often unrelated to the oxygen performance of the lens periphery. This study
      investigates a new criterion for contact lens oxygen transmissibility, the local
      Dk/t. METHOD: The study measured 20 spherical disposable lens brands (power
      range: -15.00 to +8.00 D) and 8 toric lens brands (power range: -8.00 to +4.00 D
      sphere, with a -1.00 D/-1.25 D x 180). An electro-mechanical gauge (Heidenhain,
      Germany) was used to measure lens thickness (t) at different positions on the
      lens. Oxygen permeability (Dk) of each lens material was calculated from the
      equation Dk =1.67 e (0.0397 x water content) of Morgan and Efron [Contact Lens
      Anterior Eye 21 (1998) 3] who used ISO/ANSI standard methodologies. The local
      Dk/t value was calculated from the point of maximum thickness on the lens and
      compared to the criterion of 12 Fatt units set by Benjamin [Int. Contact Lens
      Clin. 23 (1996) 188], to provide corneal oxygenation greater than or comparable
      to that available in the normal closed eye. RESULTS: All lens types with a water
      content over 65% had a local Dk/t of 12 Fatt units or more for most or all lens
      powers: CIBAVision FocusDailies, Bausch & Lomb Soflens66, CooperVision
      Actifresh400, and CIBAVision PrecisionUV. In addition, some lenses in the 55-62%
      water content range had some lens powers with a local Dk/t in excess of 12:
      CooperVision Proclear, Johnson & Johnson Acuvue 1 and CIBAVision Focus 2 week.
      None of the disposable toric lenses had a minimum Dk/t of 12 or more. The
      silicone-hydrogels, Bausch & Lomb PureVision and CIBAVision Focus Night&Day,
      comfortably exceeded Dk/t of 50 for all lens powers. CONCLUSION: Some current
      disposable soft lenses have local Dk/t values below physiological requirements.
      Contact lens manufacturers and international standards organisations should
      consider introducing the labelling of local Dk/t values on lens packaging so that
      clinicians can make informed prescribing decisions.

PMID- 16303518
TI  - The neonatal tear film.
AB  - The importance of the tear film for the integrity of the ocular surface is well
      established. Full-term neonates produce tears normally, but low spontaneous blink
      rates during early life raises important questions regarding tear dynamics and
      stability. Although an afferent neural pathway that could potentially detect tear
      break-up is in place at birth, there is indirect evidence that the neonatal tear
      film is adapted to resist evaporation-mediated tear thinning. This adaptation
      presumably prevents drying of the ocular surface during long inter-blink periods.
      However, low rates of tear turnover may have important implications for the
      defence of the eye against potential pathogens.

PMID- 16303519
TI  - Professionalism had changed.

PMID- 16303520
TI  - Relative primary adhesion of Pseudomonas aeruginosa, Serratia marcescens and
      Staphylococcus aureus to HEMA-type contact lenses and an extended wear silicone
      hydrogel contact lens of high oxygen permeability.
AB  - PURPOSE: To compare multiple strains of Pseudomonas aeruginosa and representative
      isolates of Staphylococcus aureus and Serratia marcescens for their relative
      primary adhesion to a high Dk silicone hydrogel lens (36% H2O) with that of a
      HEMA-type lens (58% H2O). METHODS: A radiolabeled cell procedure with a 2-h cell
      exposure was employed for enumerating bacteria on unworn and worn silicone
      hydrogel (balafilcon A) and HEMA-type (etafilcon A) hydrogel lenses. RESULTS: The
      degree of primary adhesion of P. aeruginosa to 7-day worn balafilcon A lens was
      similar to the degree of adhesion to unworn balafilcon A lenses. The degree of
      primary adhesion by clinical strains to unworn balafilcon A lenses and etafilcon
      lenses was strain variable, but did not differ markedly for the two lenses with a
      given strain of P. aeruginosa. Relative to most of the pseudomonad strains,
      adhesion to the hydrogel lenses by S. aureus and S. marcescens was non
      significant. CONCLUSION: Adhesion of strains of P. aeruginosa to a hydrogel
      contact lens does not appear to differ appreciably between the HEMA-type
      etafilcon A and the high Dk silicone hydrogel balafilcon A lens.

PMID- 16303521
TI  - Is contact lens "T" still important?
AB  - We studied oxygen supply to the contact lens covered cornea by means of a complex
      calculation method. We measured lens thicknesses, both centrally and at a 3mm
      peripheral location, of a range of optical powers of two different spherical
      silicone hydrogel contact lens designs (manufactured by Ciba Vision and Bausch &
      Lomb) and one "traditional" hydrogel. Using the measured values of lens thickness
      and the nominal oxygen permeabilities of these three plastics, we calculated the
      oxygen tension level in the tear layer posterior to the contact lens and anterior
      to the cornea and the oxygen flux through these contact lenses, under both open-
      and closed-eye conditions. We conclude that variable thicknesses of the silicone
      hydrogel contact lenses does not significantly affect the oxygen tension in the
      entrapped tear layer, given their high oxygen diffusion coefficients, under open
      eye conditions, and probably only minimally under closed-eye conditions as well.

PMID- 16303522
TI  - Tear turnover rate is reduced in patients with symptomatic dry eye.
AB  - PURPOSE: Tear turnover rate (TTR) is defined as the percent decrease of
      fluorescein concentration in the tears per minute after the instillation of
      fluorescein. The purpose of this study was to examine differences in TTR in a
      sample with symptoms of dry eye and an asymptomatic control sample using the
      Fluorotron Master Fluorophotometer. METHODS: TTR was measured using the
      OcuMetrics Fluorotron Master. It measures the decay of the fluorescence of high
      molecular weight fluorescein FITC Dextran instilled into the tear film. Twenty
      participants (post-menopausal women) were enrolled in the study (10 asymptomatic
      (age 64.7 +/- 6.99) and 10 symptomatic (age 61.5 +/- 7.98)). Participants were
      grouped according to either a positive (symptomatic) or negative (asymptomatic)
      McMonnies Dry Eye Questionnaire, i.e., an indication of self-reported ocular
      dryness and the use of rewetting/lubricating drops (questions 4 and 5). TTR was
      measured in the afternoon only. Measurements were made on the right eye with a
      controlled blink rate (15 blinks/min), for up to 30 min, post-insertion of 2
      microl of 2% FITC Dextran (MW 9500). The scan data were used to construct a graph
      of log fluorescein concentration (ng/ml) as a function of time and the TTR
      calculated (%/ min = (1- ln (slope)) x 100). RESULTS: There was a significant
      difference in the TTR between symptomatic and asymptomatic subjects. Mean TTR
      (symptomatic) was 4.89 +/-2.74%/min (range, 2.04-11.81) and mean TTR
      (asymptomatic) was 11.85 +/- 3.31%/min (range, 5.76-16.45) (P < 0.0001).
      CONCLUSIONS: Fluorophotometry may be used to demonstrate differences in the tear
      turnover rate in this post-menopausal group of women, with patients experiencing
      symptoms of dry eye having a lower TTR than the normals.

PMID- 16303523
TI  - Osmolality and buffering agents in soft contact lens packaging solutions.
AB  - AIM: The study determined the effects of packaging solution osmolality and
      buffering agent on soft contact lens parameters. METHODS: One lens type from each
      FDA contact lens material category was equilibrated to phosphate buffered saline
      (PBS) or borate buffered saline (BBS), at three osmolality concentrations: 270,
      310 and 414 mOsmol/kg. Lens diameter (LD), base curve (BOZR) and back vertex
      power (BVP) were measured and compared to nominal packaging label values.
      RESULTS: Statistically significant differences were found in all three parameters
      across all osmolality levels for both buffering agents. Etafilcon A showed the
      largest amount of parameter change, followed by alphafilcon A and balafilcon A.
      Lotrafilcon A was the least affected. LD of alphafilcon A lenses (greater than +/
      0.2 mm) and BVP of lotrafilcon A and etafilcon A lenses (greater than +/- 0.25
      D) measured outside the International Standards Organization (ISO) tolerance from
      their packaging labels when measured in solutions that mimicked their packaging
      solutions. CONCLUSION: Osmolality and buffering agents influence lens parameters.
      Packaging solutions can vary the parameters of some lens types from their nominal
      value to outside the tolerance range set by ISO.

PMID- 16303524
TI  - Management options for the flat corneal graft.
AB  - The post-penetrating keratoplasty (PK) corneal profile may be unpredictable and
      visual rehabilitation can be difficult. A case series of 11 such patients with
      flat corneal topography is presented and their management described. Suture
      removal may not provide a sufficient re-modelling effect to restore convexity of
      the cornea to enable satisfactory contact lens fitting and reverse geometry (RG)
      lenses have an important role.

PMID- 16303525
TI  - Non-contact tonometry over soft contact lenses: effect of contact lens power on
      the measurement of intra-ocular pressure.
AB  - PURPOSE: To perform non-contact applanation tonometry over soft contact lenses
      and to examine any differences between the measured IOPs with and without the
      contact lens. METHOD: IOP was measured at one eye of eight subjects and re
      evaluated through a soft lens in situ over the cornea. Seventy percent (ES70,
      Lunelle) water contact lenses or powers ranging from -15.00 D to +13.00 D were
      used. RESULTS: Mean IOP without lenses was 15.2 mmHg (S.D. = +/-4.2) and this did
      not change significantly for lenses ranging from -15.00 D to +3.00 D (P > 0.01)
      but did change for lens powers +6.00 D and above (P<0.01). The least squares line
      describing the change in measured IOP (deltaIOP) as a function of lens power (x)
      has the following characteristics, deltaIOP = 0.022 + 0.591x + 0.11x2 + 0.005x3
      (r = 0.985, P = 0.0001). CONCLUSION: Non-contact tonometry can be performed with
      sufficient accuracy over a soft lens on condition: (a) lens centre thickness is
      no more 0.30 mm and (b) power is not greater than +3D.

PMID- 16303526
TI  - Efficacy of continuous wear PureVision contact lenses for therapeutic use.
AB  - PURPOSE: To evaluate the Bausch and Lomb PureVision contact lens as continuous
      wear contact lens for therapeutic and medical indications in a prospective open
      ended non-randomized trial. METHODS: Patients who required therapeutic contact
      lens wear for various indications such as pain relief, corneal protection,
      persistent epithelial defects, corneal perforation and chemical burns were fitted
      with PureVision continuous wear contact lenses (balafilcon A, 36% water content).
      Success or failure of specific treatment indication was assessed in each case
      with evaluation of ocular and lens related complications. RESULTS: 30 eyes of 28
      patients were fitted with PureVision continuous wear contact lenses. A successful
      fit was seen in 27 of 30 eyes with therapeutic success in 26 of 30 eyes. However,
      all patients reported symptomatic relief. Duration of lens use ranged from 3 days
      to 3 months. Dry eye was the most frequent cause of contact lens associated
      therapeutic failure. Complications included lens loss (two eyes), tight lens (one
      eye) and infective keratitis (two eyes). CONCLUSIONS: PureVision contact lenses
      were found to be safe and efficacious for continuous wear therapeutic use to a
      maximum of 90 days. The contact lens was also easier to handle by virtue of its
      resilient nature. There were no significant corneal complications of hypoxia,
      i.e. corneal oedema. Lens losses and deposits were minimal. The lens performance
      and fitting characteristics compares favorably with previous therapeutic lenses
      used by the investigators. This new lens may be considered as a safe and
      effective alternative for use as bandage contact lens.

PMID- 16303527
TI  - Effects of benoxinate hydrochloride 0.4% on the morphological appearance of the
      cornea using confocal microscopy.
AB  - PURPOSE: To investigate whether benoxinate hydrochloride 0.4% used to make
      confocal microscopy more comfortable alters the morphology of the cornea as
      viewed with the confocal microscope. METHODS: Confocal microscopy was performed
      on both eyes of 10 subjects prior to instillation of either topical anaesthetic
      or non-preserved sterile saline, on two randomly ordered occasions. Images of all
      corneal layers were analysed quantitatively and qualitatively in a masked
      fashion. RESULTS: The images were similar in appearance in 5/10 subjects, there
      was greater clarity when anaesthetic was instilled in 4/10 subjects, and in the
      remaining subject there was greater clarity when saline was used. Anaesthetic had
      no influence on anterior keratocyte density (AKD), posterior keratocyte density
      (PKD) or endothelial cell density (ECD). CONCLUSIONS: Local anaesthetic does not
      affect corneal morphology as imaged using the confocal microscope. However,
      failure to use anaesthetic may lead to a degradation of image quality due to
      patient discomfort and excessive eye movements.

PMID- 16303528
TI  - Incidence of corneal ulcer in hydrogel contact lens wearers and post-cataract
      endophthalmitis. Do they Compare?

PMID- 16303530
TI  - Confocal microscopy of the corneas of long-term rigid contact lens wearers.
AB  - Slit scanning confocal microscopy (Tomey Confoscan P4) was used to evaluate the
      central cornea of 22 subjects who had been wearing rigid lenses on a long-term,
      daily wear basis. Anterior and posterior keratocyte densities appeared unaffected
      by rigid lens wear (P = 0.10 and 0.34 for anterior and posterior keratocyte
      densities, respectively). Subjects with a previous history of polymethyl
      methacrylate (PMMA) lens wear showed a reduction in anterior keratocyte density
      (AKD) (P < 0.0001) and an increased level of haze in the anterior stroma. This
      may represent previous hypoxic damage. Endothelial cell density (ECD) was
      unaffected by rigid lens wear (P = 0.36) although an increase in endothelial
      polymegethism was evident (P < 0.0001). Subjects who had only worn rigid lenses
      with no history of PMMA lens wear did not show an increase in endothelial
      polymegethism (P = 0.10). An increased number of microdot opacities compared to
      the non-lens wearing eye was apparent (P = 0.05). The number of microdot
      opacities induced by rigid lenses, as reported in this study, appears to be less
      than that reported by others in respect of soft lenses.

PMID- 16303531
TI  - Clinical performance of 'no rub' multi-purpose solutions.
AB  - This was a multi-site, 231-subject double-masked, bilateral crossover study to
      evaluate subjective comfort and satisfaction, corneal staining and lens deposits
      with two 'no rub' multi-purpose solutions (MPS) used with FDA Group II
      (alphafilcon A, SofLens 66, Bausch & Lomb) and Group IV (etafilcon A, SUREVUE,
      Johnson & Johnson Vision Care) soft contact lenses. Subjects used each of the two
      MPS, Regimen 1 (OPTI-FREE EXPRESS Multi-Purpose Disinfecting Solution No Rub
      Lasting Comfort Formula, Alcon Laboratories) and Regimen 2 (ReNu MultiPlus Multi
      Purpose Solution, Bausch & Lomb), for 28 days. They wore the same lens type for
      the duration of the study and were evaluated on days 0, 14 and 28 of each
      treatment period. Subjective ratings of comfort and satisfaction were
      significantly different between regimens, with the majority of variables in
      favour of Regimen 1 (P < 0.05). Corneal staining was significantly greater with
      the Group II, Regimen 2 combination (P < 0.0001). Group IV lenses cared for with
      Regimen 1 had significantly less residual lysozyme on Day 28 (562 microg) than
      lenses cared for with Regimen 2 (1145 microg; P < 0.0001). While both products
      offer the convenience of a 'no rub' regimen, differences in performance should be
      considered when recommending these solutions to patients.

PMID- 16303532
TI  - Compliance amongst contact lens wearers: comprehension skills and reinforcement
      with written instructions.
AB  - Patient non-compliance is one of the key issues when considering contact lens
      failures and related ocular complications. Patient education is believed to be of
      paramount importance to improve compliance, especially when this education
      consists of written as well as oral instructions. METHODS: Patients received oral
      or oral plus written information depending on their score from a previously
      validated oral and written comprehension test. A survey containing theoretical
      and practical questions was given to the patient at the end of the study in order
      to establish compliance with the given instructions. RESULTS: No statistically
      significant difference was encountered between the group of patients receiving
      oral instructions only and the group receiving oral plus written information. A
      correlation was discovered between non-compliance and ocular complications and
      between ocular complications and the physical appearance of contact lenses and
      cases. DISCUSSION: The oral and written comprehension test served to establish
      the comprehension skills typology of the patients, thus allowing for the
      appropriate type of instructions (oral or written) to be given to each patient in
      accordance with their particular abilities. This methodology could lead to a
      relevant increase in compliance.

PMID- 16303534
TI  - Contact lenses--now, and then.

PMID- 16303533
TI  - Why one million contact lens wearers dropped out.

PMID- 16303535
TI  - Parameter stability of soft contact lenses made from different materials.
AB  - The parameters of soft contact lenses may alter during wear. A series of clinical
      and laboratory experiments were conducted in order to examine the parameter
      stability of eight soft contact lenses manufactured from different materials. The
      following materials (and nominal water contents) were used: HEMA/VP 40%, HEMA/VP
      55%, HEMA/VP 70%, VP/MMA 55%, VP/MMA 70%, HEMA 40%, HEMA/MAA 55% and HEMA/MAA 70%
      (HEMA: 2-hydroxy-ethyl methacrylate, VP: vinyl pyrrolidone, MMA: methyl
      methacrylate, MAA: methacrylic acid). Two lenses from each of the eight soft
      contact lens groups were used in experiments concerning the parameter stability.
      Six subjects were fitted with lenses for 1 day. Verification of back optic zone
      radius, total diameter, back vertex power, centre thickness and water content was
      undertaken at 20 degrees C. In vitro measurements of water content, oxygen
      transmissibility, total diameter and back optic zone radius were taken at 35
      degrees C before lens fitting and after 6h of lens wear. Distortion,
      discolouration and lens quality were assessed before and after lens wear. When
      the temperature was raised from 20 to 35 degrees C, a significant reduction in
      lens water content for all the lens types was observed, as well as a significant
      reduction in total lens diameter for the majority of the lens types. Water
      content, oxygen transmissibility, total diameter and back optic zone radius of
      all the lens types reduced, following a 6h open eye wearing period. For the
      majority of the lens types, these changes were found to be statistically
      significant. Distortion, discolouration and quality of the lenses remained
      unchanged throughout the study with the exception of the HEMA/MAA 70% lens.
      Correlating a number of parameters generated in this study, gave the following
      conclusions. High water content materials exhibit a low relative change in oxygen
      transmissibility following a 6h wear period. Soft contact lens dehydration leads
      to a decrease in oxygen transmissibility and total diameter, following a 6h wear
      period. These results will assist practitioners in predicting the alterations
      that occur in soft contact lens parameters and oxygen performance as a result of
      lens wear.

PMID- 16303536
TI  - In-eye performance of soft contact lenses made from different materials.
AB  - The in-eye performance of soft contact lenses may be affected by the material
      from which they are fabricated and may alter during wear. This study describes
      clinical and laboratory experiments that were conducted in order to examine the
      in-eye performance of eight soft contact lenses manufactured from different
      materials; these materials (and nominal water contents) were: HEMA/VP 40%,
      HEMA/VP 55%, HEMA/VP 70%, VP/MMA 55%, VP/MMA 70%, HEMA 40%, HEMA/MAA 55% and
      HEMA/MAA 70% (HEMA: 2-hydroxy-ethyl methacrylate, VP: vinyl pyrrolidone, MMA:
      methyl methacrylate, MAA: methacrylic acid). Two lenses from each of the eight
      soft contact lens groups were used in experiments concerning their parameter
      stability. Six subjects were fitted with lenses for 1 day. Verification of back
      optic zone radius, total diameter, back vertex power, centre thickness and water
      content was undertaken at 20 degrees C. In vitro measurements of total diameter
      were taken at 35 degrees C before lens fitting and after 6 h of lens wear. In
      vivo measurements of lens centration, up-gaze lag, post-blink movement, total
      diameter and subjective assessment of comfort were taken (a) immediately after
      lens insertion (1 min), (b) 20 min later and (c) 6 h later (same day). The
      majority of differences of the in vivo parameters between lens types (with
      respect to lens centration, lag, movement on blink, lens total diameter and
      comfort) were not found to be statistically significant throughout the 6 h
      wearing period. It was also found that lenses increase in diameter when first
      placed on the eye and decrease in diameter when they were removed from the eye.
      The information generated in study concerning the in-eye performance of soft
      contact lens materials may assist the contact lens industry and contact lens
      practitioners in developing and prescribing soft lenses with optimal performance
      characteristics.

PMID- 16303537
TI  - Contribution of regimen steps to disinfection of hydrophilic contact lenses.
AB  - The effect of regimen steps on overall performance of contact lens disinfection
      processes was evaluated. Hydrophilic lenses were inoculated with Staphylococcus
      aureus, Pseudomonas aeruginosa, Serratia marcescens, Candida albicans, or
      Fusarium solani. Contributions of regimen steps and rinse volumes to disinfection
      abilities of OPTI-FREE EXPRESS, Solo-care Plus (Ciba Vision), Complete
      (Allergan), and ReNu MultiPlus (Bausch & Lomb) multi-purpose solutions were
      examined. Numbers of surviving microorganisms were determined. Results showed
      that the number and timing of regimen steps was directly related to performance
      of products. OPTI-FREE EXPRESS solution showed fewer survivors than did other
      products. Minimizing regimen steps could adversely affect product efficacy.

PMID- 16303539
TI  - Grading of corneal transparency.
AB  - AIM: To examine the academic literature on the grading of corneal transparency
      and to assess the potential use of objective image analysis. METHOD: Reference
      databases of academic literature were searched and relevant manuscripts reviewed.
      Annunziato, Efron (Millennium Edition) and Vistakon-Synoptik corneal oedema
      grading scale images were analysed objectively for relative intensity, edges
      detected, variation in intensity and maximum intensity. In addition, corneal
      oedema was induced in one subject using a low oxygen transmissibility (Dk/t)
      hydrogel contact lens worn for 3h under a light eye patch. Recovery from oedema
      was monitored over time using ultrasound pachymetry, high and low contrast visual
      acuity measures, bulbar hyperaemia grading and transparency image analysis of the
      test and control eyes. RESULTS: Several methods for assessing corneal
      transparency are described in the academic literature, but none have gained
      widespread use in clinical practice. The change in objective image analysis with
      printed scale grade was best described by quadratic parametric or sigmoid 3
      parameter functions. 'Pupil image scales' (Annunziato and Vistakon-Synoptik) were
      best correlated to average intensity; however, the corneal section scale (Efron)
      was strongly correlated to variations in intensity. As expected, patching an eye
      wearing a low Dk/t hydrogel contact lens caused a significant (F = 119.2, p <
      0.001) 14.3% increase in corneal thickness, which gradually recovered under open
      eye conditions. Corneal section image analysis was the most affected parameter
      and intensity variation across the slit width, in isolation, was the strongest
      correlate, accounting for 85.8% of the variance with time following patching, and
      88.7% of the variance with corneal thickness. CONCLUSION: Corneal oedema is best
      determined objectively by the intensity variation across the width of a corneal
      section. This can be easily measured using a slit-lamp camera connected to a
      computer. Oedema due to soft contact lens wear is not easily determined over the
      pupil area by sclerotic scatter illumination techniques.

PMID- 16303540
TI  - Surgical management of presbyopia.
AB  - Presbyopia is age-related reduction in amplitude of accommodation and the loss of
      the ability to change the eye's focus from far to near. It is the one of the most
      common age-related ailment. Traditional methods such as spectacle glasses or
      contact lenses are still the most widely used for correction of the problem. This
      article is an attempt to review the surgical options available for presbyopia.

PMID- 16303541
TI  - Tensile properties of soft contact lens materials.
AB  - The strength of contact lens materials is an important consideration with respect
      to resistance to damage during lens handling and long term durability, and may
      govern some aspects of in-eye lens performance. The tensile properties of
      hydrogel contact lenses manufactured from eight different materials were examined
      in a series of clinical and laboratory experiments using the Instron 1122
      Universal Testing Instrument. Lenses from the following eight materials (and
      nominal water contents) were used: HEMA/VP 40%, HEMA/VP 55%, HEMA/VP 70%, VP/MMA
      55%, VP/MMA 70%, HEMA 40%, HEMA/MAA 55% and HEMA/MAA 70% (HEMA: 2-hydroxy-ethyl
      methacrylate, VP: vinyl pyrrolidone, MMA: methyl methacrylate, MAA: methacrylic
      acid). Tensile strength, elongation-at-break and Young's modulus were measured. A
      technique was devised that enables three parallel-sided specimens of identical
      width to be cut from a single contact lens with good accuracy. It was found that
      materials made from HEMA/MAA--although having a very low tensile strength and
      elongation-at-break--exhibit only a moderate Young's modulus. Materials made from
      HEMA/VP exhibit high-to-moderate tensile strength, high elongation-at-break and
      moderate-to-low Young's modulus. Materials made from VP/MMA exhibit high tensile
      strength and high-to-moderate elongation-at-break, but the Young's modulus is
      high for the 55% water content and low for the 70% water content materials. The
      HEMA 40% material exhibits a moderate tensile strength, a low elongation-at-break
      and a high Young's modulus. This experiment highlights the necessity of
      developing an accepted standard test methodology for contact lens material
      stiffness evaluation, in order to derive useful comparative information. Six
      subjects were fitted with the same lenses for one day. In vitro measurements of
      total diameter and back optic zone radius were taken at 35 degrees C before lens
      fitting and after 6h of lens wear. Lens water content, the relative change in
      lens total diameter (%deltaTD) and relative change in lens back optic zone radius
      (%deltaBOZR) were calculated and correlated with the tensile properties of the
      eight hydrogel lens materials. It is concluded that hydrogel materials with high
      stiffness and strength display less tendency to change their geometric parameters
      and materials with a high water content do not necessarily have the weakest
      mechanical properties.

PMID- 16303542
TI  - Water properties of soft contact lens materials.
AB  - The properties of water in soft contact lenses such as the water content, free-to
      bound water ratio, and the extent to which soft lenses dehydrate during wear, are
      key determinants of their in eye performance and oxygen transmissibility
      characteristics. This study describes clinical and laboratory experiments that
      were conducted in order to examine the state of water in eight soft contact
      lenses manufactured from different materials. Specifically, lenses made from the
      following eight materials (and nominal water contents) were used: HEMA/VP 40%,
      HEMA/VP 55%, HEMA/VP 70%, VP/MMA 55%, VP/MMA 70%, HEMA 40%, HEMA/MAA 55% and
      HEMA/MAA 70% [HEMA = 2-hydroxy-ethyl methacrylate, VP = vinyl pyrrolidone, MMA =
      methyl methacrylate, MAA = methacrylic acid]. Differential scanning calorimetry
      (DSC) was used for measuring the free water content in the materials listed
      above. Some noticeable differences in water properties among soft contact lens
      materials having approximately the same water contents were revealed. Low water
      content materials exhibited a simple endotherm and all water melted around 0
      degrees C. On the other hand, medium and high water content materials exhibited
      multiple melting endotherms, representing a broad range of interactions between
      water and the polymer. Low water content soft contact lenses have approximately
      the same amount of bound water as those with much higher water contents. Six
      subjects were then fitted with the same lenses for one day. In vitro measurements
      of water content and oxygen transmissibility were taken at 35 degrees C, both
      before lens fitting and after 6 h of lens wear. Water content and oxygen
      transmissibility were correlated with the water properties of the soft contact
      lens materials. The relative change in lens water content (%deltaWC) and relative
      change in lens oxygen transmissibility (%deltaDk/t) were calculated and
      correlated with the water properties of the eight soft contact lens materials. It
      was concluded that (a) oxygen transmissibility, free water content and free-to
      bound water ratio are increased when the water content of a contact lens is
      increased and (b) water content, free water content and free-to-bound water ratio
      cannot be used for the prediction of soft contact lens dehydration in vivo.

PMID- 16303544
TI  - The unfolded protein response.

PMID- 16303545
TI  - Chordates.

PMID- 16303546
TI  - Selection for tameness has changed brain gene expression in silver foxes.

PMID- 16303547
TI  - Vision: a brake on the speed of sight.
AB  - We move our eyes more often than our heart beats. Our brain seems to cope
      effortlessly with the consequences of these rapid visual alterations, but a new
      study shows that similar scene changes in the absence of eye movements delay the
      speed of information processing. So are there costs in constantly shifting our
      focus of gaze?

PMID- 16303548
TI  - Evolution: natural selection in the evolution of humans and chimps.
AB  - We now have more or less full sequences of both human and chimp genomes, allowing
      comparison that sheds light on their evolution. A few hundred genes show
      significant evidence for adaptive evolution in the two lineages, but the actual
      number might be much higher. Natural selection has eliminated about 75% of amino
      acid changes in coding sequence since the split of the human and chimpanzee
      genomes.

PMID- 16303549
TI  - Infectious disease: can we avert a lethal flu pandemic?
AB  - If avian flu becomes directly transmissible among humans, could we prevent a
      pandemic by using prophylactic antivirals? Possibly, if the virus is not too
      transmissible, and we react fast and efficiently.

PMID- 16303550
TI  - Eye development: stable cell fate decisions in insect colour vision.
AB  - The retina provides an example of a fundamental property of developing cells:
      cell fate decisions are stable. A recent paper reports a double negative feedback
      loop that leads to bistable fate decisions in the colour-detecting photoreceptors
      of Drosophila.

PMID- 16303551
TI  - Ecological succession: out of the ash.
AB  - A new study of plants recolonising the land devasted when Mount St. Helens
      erupted in 1980 is providing important new insights into the interactions with
      herbivores that determine the pattern and outcome of ecological succession.

PMID- 16303552
TI  - Mate choice: female relatives share sexual partners in bats.
AB  - Groups of female greater horseshoe bats share more than just caves. A long-term
      study has revealed that female relatives share males as well, but the adaptive
      significance of this family-wide mate fidelity remains obscure.

PMID- 16303553
TI  - Photosynthesis: the processing of redox signals in chloroplasts.
AB  - Recent work identifies two kinases required for phosphorylation of proteins of
      chloroplast thylakoid membranes. One kinase, STN7, is required for
      phosphorylation of light-harvesting complex II; another, STN8, is required for
      phosphorylation of photosystem II. How do these kinases interact, what do they
      do, and what are they for?

PMID- 16303554
TI  - Drosophila memory: dopamine signals punishment?
AB  - Dopamine-containing neurons are widespread in the fly brain and have been
      implicated in negatively reinforced memory. Current technology allows the
      investigator to watch dopaminergic neurons in action in the brain of a learning
      fly.

PMID- 16303555
TI  - Fungal CO2 sensing: a breath of fresh air.
AB  - Carbon dioxide levels are used by two fungal pathogens as a key signal to choose
      between the expression of environmental or virulence traits. Studies now reveal
      that the atypical fungal adenylyl cyclases are implicated in this decision.

PMID- 16303556
TI  - Length control of the metaphase spindle.
AB  - BACKGROUND: The pole-to-pole distance of the metaphase spindle is reasonably
      constant in a given cell type; in the case of vertebrate female oocytes, this
      steady-state length can be maintained for substantial lengths of time, during
      which time microtubules remain highly dynamic. Although a number of molecular
      perturbations have been shown to influence spindle length, a global understanding
      of the factors that determine metaphase spindle length has not been achieved.
      RESULTS: Using the Drosophila S2 cell line, we depleted or overexpressed proteins
      that either generate sliding forces between spindle microtubules (Kinesin-5,
      Kinesin-14, dynein), promote microtubule polymerization (EB1, Mast/Orbit [CLASP],
      Minispindles [Dis1/XMAP215/TOG]) or depolymerization (Kinesin-8, Kinesin-13), or
      mediate sister-chromatid cohesion (Rad21) in order to explore how these forces
      influence spindle length. Using high-throughput automated microscopy and
      semiautomated image analyses of >4000 spindles, we found a reduction in spindle
      size after RNAi of microtubule-polymerizing factors or overexpression of Kinesin
      8, whereas longer spindles resulted from the knockdown of Rad21, Kinesin-8, or
      Kinesin-13. In contrast, and differing from previous reports, bipolar spindle
      length is relatively insensitive to increases in motor-generated sliding forces.
      However, an ultrasensitive monopolar-to-bipolar transition in spindle
      architecture was observed at a critical concentration of the Kinesin-5 sliding
      motor. These observations could be explained by a quantitative model that
      proposes a coupling between microtubule depolymerization rates and microtubule
      sliding forces. CONCLUSIONS: By integrating extensive RNAi with high-throughput
      image-processing methodology and mathematical modeling, we reach to a conclusion
      that metaphase spindle length is sensitive to alterations in microtubule dynamics
      and sister-chromatid cohesion, but robust against alterations of microtubule
      sliding force.

PMID- 16303557
TI  - Rapid, Wnt-induced changes in GSK3beta associations that regulate beta-catenin
      stabilization are mediated by Galpha proteins.
AB  - BACKGROUND: In the absence of Wnt stimulation, the transcriptional cofactor beta
      catenin is destabilized via phosphorylation by protein kinase GSK3beta in complex
      with Axin family members. In the "canonical" Wnt signaling pathway, Disheveled
      (Dvl) is required to functionally inhibit the activity of the GSK3beta/Axin
      complex and thereby stabilize beta-catenin. Yet, the mechanisms that underlie Wnt
      regulation of GSK3 and stabilization of beta-catenin are still not fully
      appreciated. RESULTS: Here, we examine time-dependent changes in protein-protein
      interactions that occur in response to Wnt treatment. We show that GSK3beta/Axin
      complexes are rapidly (t1/2 < 3 min) disrupted upon Wnt stimulation and that
      changes in GSK3beta/Axin association substantially precede both beta-catenin
      stabilization and Axin degradation. We further demonstrate that depletion of
      Galpha(o) or Galpha(q) will inhibit, respectively, the Wnt-induced disruption of
      GSK3beta/Axin2 and GSK3beta/Axin complexes and diminish Wnt stabilization of beta
      catenin. We also show that direct activation of G proteins in vivo with GTPgammaS
      in the absence of exogenous Wnt will disrupt GSK3beta/Axin2 complexes and
      stabilize beta-catenin. Finally, we demonstrate an association of Galpha(o) with
      Fz that is also very rapidly (t1/2 < 1 min) perturbed upon Wnt-3a stimulation and
      that the Wnt-dependent effects on both GSK3beta/Axin2 and Galpha(o)/Fz are
      pertussis-toxin sensitive. Collectively, these data implicate a role for G
      proteins in the regulation of Wnt-mediated protein-protein interactions and
      signaling to beta-catenin. CONCLUSIONS: We conclude that rapid disruption of
      GSK3beta/Axin interactions in response to Wnt leads to the initial stabilization
      of beta-catenin and that Galpha(o) and Galpha(q) signaling contributes to Wnt
      mediated GSK3beta/Axin disruption and the ultimate stabilization of beta-catenin.

PMID- 16303558
TI  - Cold and light control seed germination through the bHLH transcription factor
      SPATULA.
AB  - BACKGROUND: Plants integrate signals from the environment and use these to modify
      the timing of development according to seasonal cues. Seed germination is a key
      example of this phenomenon and in Arabidopsis is promoted by the synergistic
      interaction of light and low temperatures in dormant seeds. This signaling
      pathway is known to converge on the regulation of the gibberellin (GA)
      biosynthetic genes GA3 oxidase (GA3ox), whose expression is transcriptionally
      induced by light and cold in imbibed seeds. However, the molecular basis of this
      response has until now been unknown. RESULTS: Here we show that the bHLH
      transcription factor SPATULA is a light-stable repressor of seed germination and
      mediates the germination response to temperature. Furthermore, SPT is required in
      dormant seeds for maintaining the repression of GA3ox transcription. We also show
      that the related protein PIL5 represses seed germination and GA3ox expression in
      the dark. CONCLUSIONS: We conclude that SPT and PIL5 form part of a regulatory
      network coupling seed germination and GA3ox expression to light and temperature
      signaling in the seed.

PMID- 16303559
TI  - A role for mammalian diaphanous-related formins in complement receptor (CR3)
      mediated phagocytosis in macrophages.
AB  - Macrophages, dendritic cells, and neutrophils use phagocytosis to capture and
      clear off invading pathogens. The process is triggered by the interaction of
      ligands on the pathogens' surface with specific phagocytic receptors, including
      immunoglobulin (FcR) and complement C3bi (CR3) receptors (integrin alpha(M)beta2,
      Mac1) . Localized actin-filament assembly that acts as the driving force for
      particle engulfment is controlled by Rho-family small GTPases . RhoA regulates
      CR3-mediated phagocytosis through a mechanism that is still unclear . Mammalian
      Diaphanous-related (mDia) formins participate in the generation of a diverse set
      of actin-remodeling events downstream of RhoA , and mDia1 is recruited around
      fibronectin-coated beads in a RhoA-dependent manner in fibroblasts . Here, we set
      out to examine whether mDia proteins are involved in CR3-mediated phagocytosis in
      macrophages. We show that the RhoA effector mDia1 is recruited early during CR3
      mediated phagocytosis and colocalizes with polymerized actin in the phagocytic
      cup. Interfering with mDia activity inhibits CR3-mediated phagocytosis while
      having no effect on FcR-mediated phagocytosis. These results indicate a new
      function for mDia proteins in the regulation of actin polymerization during CR3
      mediated phagocytosis.

PMID- 16303560
TI  - Carbonic anhydrase and CO2 sensing during Cryptococcus neoformans growth,
      differentiation, and virulence.
AB  - The gas carbon dioxide (CO2) plays a critical role in microbial and mammalian
      respiration, photosynthesis in algae and plants, chemoreception in insects, and
      even global warming . However, how CO2 is transported, sensed, and metabolized by
      microorganisms is largely not understood. For instance, CO2 is known to induce
      production of polysaccharide capsule virulence determinants in pathogenic
      bacteria and fungi via unknown mechanisms . Therefore, we studied CO2 actions in
      growth, differentiation, and virulence of the basidiomycetous human fungal
      pathogen Cryptococcus neoformans. The CAN2 gene encoding beta-carbonic anhydrase
      in C. neoformans was found to be essential for growth in environmental ambient
      conditions but dispensable for in vivo proliferation and virulence at the high
      CO2 levels in the host. The can2Delta mutant in vitro growth defect is largely
      attributable to defective fatty acid synthesis. CO2 was found to inhibit cell
      cell fusion but not filamentation during sexual reproduction. The can2 mutation
      restored early mating events in high CO2 but not later steps (fruiting body
      formation, sporulation), indicating a major role for carbonic anhydrase and
      CO2/HCO3- in this developmental cascade leading to the production of infectious
      spores. Our studies illustrate diverse roles of an ancient enzyme class in
      enabling environmental survival of a ubiquitous human pathogen.

PMID- 16303561
TI  - Fungal adenylyl cyclase integrates CO2 sensing with cAMP signaling and virulence.
AB  - The ascomycete Candida albicans is the most common fungal pathogen in
      immunocompromised patients . Its ability to change morphology, from yeast to
      filamentous forms, in response to host environmental cues is important for
      virulence . Filamentation is mediated by second messengers such as cyclic
      adenosine 3',5'-monophosphate (cAMP) synthesized by adenylyl cyclase . The
      distantly related basidiomycete Cryptococcus neoformans is an encapsulated yeast
      that predominantly infects the central nervous system in immunocompromised
      patients . Similar to the morphological change in C. albicans, capsule
      biosynthesis in C. neoformans, a major virulence attribute, is also dependent
      upon adenylyl cyclase activity . Here we demonstrate that physiological
      concentrations of CO2/HCO3- induce filamentation in C. albicans by direct
      stimulation of cyclase activity. Furthermore, we show that CO2/HCO3-
      equilibration by carbonic anhydrase is essential for pathogenesis of C. albicans
      in niches where the available CO2 is limited. We also demonstrate that adenylyl
      cyclase from C. neoformans is sensitive to physiological concentrations of
      CO2/HCO3-. These data demonstrate that the link between cAMP signaling and
      CO2/HCO3- sensing is conserved in fungi and reveal CO2 sensing to be an important
      mediator of fungal pathogenesis. Novel therapeutic agents could target this
      pathway at several levels to control fungal infections.

PMID- 16303562
TI  - Separate processing of different global-motion structures in visual cortex is
      revealed by FMRI.
AB  - The visual system has the remarkable ability to extract several types of
      meaningful global-motion signals, such as radial motion, translation motion, and
      rotation, for different visual functions and actions. In the monkey brain,
      different groups of cells in MST respond best to different types of global motion
      [1, 2] whereas in lower cortical areas including MT, no such differential
      responses have been found. Here, we show that an area (or areas) lower than MST
      in the human brain [3] responds to different types of global motion. A series of
      human functional magnetic resonance imaging (fMRI) experiments, in which
      attention was controlled for, indicated that the center of radial motion
      activates the corresponding location in the V3A representation, whereas
      translation motion activates mainly in a more peripheral representation of V3A.
      These results suggest that in the human brain, V3A is an area that differentially
      responds according to the type of global motion.

PMID- 16303563
TI  - Cdc28-dependent regulation of the Cdc5/Polo kinase.
AB  - Polo kinase is activated as cells enter mitosis and plays a central role in
      coordinating diverse mitotic events, yet the mechanisms leading to activation of
      Polo kinase are poorly understood . Work in Xenopus meiotic cell cycles has
      suggested that Polo kinase functions in a pathway that helps trigger activation
      of Cdk1 . However, studies in other organisms have suggested that activation of
      Polo kinase is dependent upon Cdk1 and therefore occurs downstream of Cdk1
      activation . In this study, we have investigated the role of Cdk1 in the
      activation of budding yeast Polo kinase. The budding yeast homologs of Cdk1 and
      Polo kinase are referred to as Cdc28 and Cdc5. We show that signaling from Cdc28
      is required to maintain Cdc5 activity in vivo. Furthermore, purified Cdc28
      associated with the mitotic cyclin Clb2 is sufficient to activate purified Cdc5
      in vitro. A single Cdc28 consensus phosphorylation site found at threonine 242 in
      the activation loop segment of Cdc5 is required for Cdc5 function in vivo and for
      kinase activity in vitro, whereas four other Cdc28 consensus sites are
      dispensable. Analysis of Cdc5 phosphorylation by mass spectrometry indicates that
      threonine 242 is phosphorylated in vivo. These results suggest that Cdc28
      activates Cdc5 via phosphorylation of threonine 242.

PMID- 16303564
TI  - A miRNA involved in phosphate-starvation response in Arabidopsis.
AB  - Although microRNAs (miRNAs) have been documented to regulate development in
      plants and animals , the function of miRNAs in physiology is unclear. miR399 has
      multiple target sites in the 5' untranslated region (UTR) of a gene encoding a
      putative ubiquitin-conjugating enzyme (UBC) in Arabidopsis thaliana. We report
      here that miR399 was highly induced, whereas the target UBC mRNA was reduced by
      low-phosphate (Pi) stress. In transgenic plants with constitutive expression of
      miR399, UBC mRNA accumulation was suppressed even under high Pi. The expression
      of transgene UBC mRNA with 5' UTR miR399 target sites, but not the one without 5'
      UTR, was reduced under low-Pi condition. Furthermore, transgenic Arabidopsis
      plants with constitutive expression of miR399 accumulated more Pi than the wild
      type, and transgenic plants expressing the UBC mRNA without 5' UTR (miRNA
      deregulated) showed less inhibition of primary root growth and less induction of
      a Pi transporter gene by low-Pi stress than those of wild-type plants. We
      conclude that miR399 downregulates UBC mRNA accumulation by targeting the 5' UTR,
      and this regulation is important for plant responses to Pi starvation. The
      results suggest that miRNAs have functional roles for plants to cope with
      fluctuations in mineral-nutrient availability in the soil.

PMID- 16303566
TI  - Gigaxonin interacts with tubulin folding cofactor B and controls its degradation
      through the ubiquitin-proteasome pathway.
AB  - Gigaxonin is mutated in human giant axonal neuropathy (GAN), an autosomal
      recessive neurodegenerative disorder. The presence of generalized cytoskeletal
      abnormalities , including few microtubules and accumulated intermediate filaments
      (IFs), in GAN suggests an essential role of gigaxonin in cytoskeletal
      organization and dynamics. However, the molecular mechanisms underlying the
      cytoskeletal pathology remain to be elucidated. Over the years, the ubiquitin
      proteasome system (UPS) of intracellular protein degradation has been implicated
      in the control of many fundamental cellular processes. Defects in this system
      seem to be directly linked to the development of human diseases, including
      cancers and neurodegenerative diseases . Here, we show that gigaxonin controls
      protein degradation of tubulin folding cofactor B (TBCB) , a function disrupted
      by GAN-associated mutations. The substantial TBCB protein accumulation caused by
      impaired UPS may be a causative factor of cytoskeletal pathology in GAN. Our
      study provides important insight into pathogenesis of neurodegenerative diseases
      associated with cytoskeletal abnormalities.

PMID- 16303565
TI  - Replication-independent histone deposition by the HIR complex and Asf1.
AB  - The orderly deposition of histones onto DNA is mediated by conserved assembly
      complexes, including chromatin assembly factor-1 (CAF-1) and the Hir proteins .
      CAF-1 and the Hir proteins operate in distinct but functionally overlapping
      histone deposition pathways in vivo . The Hir proteins and CAF-1 share a common
      partner, the highly conserved histone H3/H4 binding protein Asf1, which binds the
      middle subunit of CAF-1 as well as to Hir proteins . Asf1 binds to newly
      synthesized histones H3/H4 , and this complex stimulates histone deposition by
      CAF-1 . In yeast, Asf1 is required for the contribution of the Hir proteins to
      gene silencing . Here, we demonstrate that Hir1, Hir2, Hir3, and Hpc2 comprise
      the HIR complex, which copurifies with the histone deposition protein Asf1.
      Together, the HIR complex and Asf1 deposit histones onto DNA in a replication
      independent manner. Histone deposition by the HIR complex and Asf1 is impaired by
      a mutation in Asf1 that inhibits HIR binding. These data indicate that the HIR
      complex and Asf1 proteins function together as a conserved eukaryotic pathway for
      histone replacement throughout the cell cycle.

PMID- 16303568
TI  - Neuronal expression of p53 dominant-negative proteins in adult Drosophila
      melanogaster extends life span.
AB  - Hyperactivation of p53 leads to a reduction in tumor formation and an unexpected
      shortening of life span in two different model systems . The decreased life span
      occurs with signs of accelerated aging, such as osteoporosis, reduction in body
      weight, atrophy of organs, decreased stress resistance, and depletion of
      hematopoietic stem cells. These observations suggest a role for p53 in the
      determination of life span and the speculation that decreasing p53 activity may
      result in positive effects on some aging phenotypes . In this report, we show
      that expression of dominant-negative versions of Drosophila melanogaster p53 in
      adult neurons extends life span and increases genotoxic stress resistance in the
      fly. Consistent with this, a naturally occurring allele with decreased p53
      activity has been associated with extended survival in humans . Expression of the
      dominant-negative Drosophila melanogaster p53 constructs does not further
      increase the extended life span of flies that are calorie restricted, suggesting
      that a decrease in p53 activity may mediate a component of the calorie
      restriction life span-extending pathway in flies.

PMID- 16303567
TI  - A large-scale screen in S. pombe identifies seven novel genes required for
      critical meiotic events.
AB  - Meiosis is a specialized form of cell division by which sexually reproducing
      diploid organisms generate haploid gametes. During a long prophase, telomeres
      cluster into the bouquet configuration to aid chromosome pairing, and DNA
      replication is followed by high levels of recombination between homologous
      chromosomes (homologs). This recombination is important for the reductional
      segregation of homologs at the first meiotic division; without further
      replication, a second meiotic division yields haploid nuclei. In the fission
      yeast Schizosaccharomyces pombe, we have deleted 175 meiotically upregulated
      genes and found seven genes not previously reported to be critical for meiotic
      events. Three mutants (rec24, rec25, and rec27) had strongly reduced meiosis
      specific DNA double-strand breakage and recombination. One mutant (tht2) was
      deficient in karyogamy, and two (bqt1 and bqt2) were deficient in telomere
      clustering, explaining their defects in recombination and segregation. The moa1
      mutant was delayed in premeiotic S phase progression and nuclear divisions.
      Further analysis of these mutants will help elucidate the complex machinery
      governing the special behavior of meiotic chromosomes.

PMID- 16303569
TI  - Genetic basis of tetrodotoxin resistance in pufferfishes.
AB  - Tetrodotoxin (TTX) is a highly potent neurotoxin that selectively binds to the
      outer vestibule of voltage-gated sodium channels. Pufferfishes accumulate
      extremely high concentrations of TTX without any adverse effect. A nonaromatic
      amino acid (Asn) residue present in domain I of the pufferfish, Takifugu
      pardalis, Na v1.4 channel has been implicated in the TTX resistance of
      pufferfishes . However, the effect of this residue on TTX sensitivity has not
      been investigated, and it is not known if this residue is conserved in all
      pufferfishes. We have investigated the genetic basis of TTX resistance in
      pufferfishes by comparing the sodium channels from two pufferfishes (Takifugu
      rubripes [fugu] and Tetraodon nigroviridis) and the TTX-sensitive zebrafish.
      Although all three fishes contain duplicate copies of Na v1.4 channels (Na v1.4a
      and Na v1.4b), several substitutions were found in the TTX binding outer
      vestibule of the two pufferfish channels. Electrophysiological studies showed
      that the nonaromatic residue (Asn in fugu and Cys in Tetraodon) in domain I of Na
      v1.4a channels confers TTX resistance. The Glu-to-Asp mutation in domain II of
      Tetraodon channel Na v1.4b is similar to that in the saxitoxin- and TTX-resistant
      Na+ channels of softshell clams . Besides helping to deter predators, TTX
      resistance enables pufferfishes to selectively feed on TTX-bearing organisms.

PMID- 16303571
TI  - Gastrointestinal bleeding.
AB  - Gastrointestinal bleeding encompasses a broad array of clinical scenarios. The
      spectrum is diverse because of the multiple types of lesions that can cause
      bleeding, and because bleeding can occur from virtually anywhere in the
      gastrointestinal tract. The fundamental tenets of management of patients with
      gastrointestinal bleeding include the following: (1) the patient must undergo
      immediate assessment and stabilization of hemodynamic status, (2) the source of
      bleeding must be identified, (3) active bleeding should be stopped, (4) the
      underlying abnormality should be treated, and (5) recurrent bleeding should be
      "prevented.

PMID- 16303572
TI  - Nonvariceal upper gastrointestinal bleeding: epidemiology and diagnosis.
AB  - Nonvariceal upper gastrointestinal bleeding remains an important cause of patient
      morbidity, mortality, and use of considerable health care resources. An early and
      accurate diagnosis is critical for guiding appropriate management and
      facilitating patient care. This article reviews the most recent epidemiologic
      data on acute nonvariceal upper gastrointestinal bleeding and outlines important
      aspects of making the diagnosis.

PMID- 16303573
TI  - Nonvariceal upper gastrointestinal bleeding: standard and new treatment.
AB  - Nonvariceal upper gastrointestinal bleeding remains a challenging problem with a
      significant morbidity and mortality. In recent years endoscopic techniques have
      evolved, resulting in improved primary hemostasis and a reduction in the risk of
      rebleeding. Combination endoscopic therapy followed by high-dose proton pump
      inhibitor shows improved outcomes. Innovative endoscopic therapies hold promise
      but are as yet unproved. An aging population with significant medical
      comorbidities has a major influence on the overall outcome from upper
      gastrointestinal bleeding.

PMID- 16303574
TI  - Bleeding caused by portal hypertension.
AB  - Variceal bleeding is one of the dreaded complications of portal hypertension.
      Patients who have suspected or proven cirrhosis should undergo diagnostic upper
      endoscopy to detect medium and large gastro-esophageal varices. Patients with
      medium and large gastro-esophageal varices should be treated with non-selective
      beta-blockers (propranolol or nadolol), and these agents should be titrated to a
      heart rate of 55 beats per minute or adverse effects. If there are
      contraindications to or if patients are intolerant to beta-blockers, it is
      appropriate to consider prophylactic banding therapy for individuals with medium
      to-large esophageal varices. When patients who have cirrhosis present with GI
      bleeding, they should be resuscitated and receive octreotide or other vasoactive
      agents. Endoscopy should be performed promptly to diagnose the source of bleeding
      and to provide endoscopic therapy (preferably banding). The currently available
      treatment for acute variceal bleeding provides hemostasis in most patients. These
      patients, however, are at significant risk for rebleeding unless secondary
      prophylaxis is provided. Although various pharmacological, endoscopic,
      radiological, and surgical options are available, combined pharmacological and
      endoscopic therapy is the most common form of secondary prophylaxis. TIPS is a
      radiologically placed portasystemic shunt, and if placed in suitable patients, it
      can provide effective treatment for patients with variceal bleeding that is
      refractory to medical and endoscopic therapy.

PMID- 16303575
TI  - Lower GI bleeding: epidemiology and diagnosis.
AB  - Lower gastrointestinal bleeding is one of the most common gastrointestinal
      indications for hospital admission, particularly in the elderly. Diverticulosis
      accounts for up to 50% of cases, followed by ischemic colitis and anorectal
      lesions. Though most patients stop bleeding spontaneously and have favorable
      outcomes, long-term recurrence is a substantial problem for patients with
      bleeding from diverticulosis and angiodysplasia. The management of LGIB is
      challenging because of the diverse range of bleeding sources, the large extent of
      bowel involved, the intermittent nature of bleeding, and the various complicated
      and often invasive investigative modalities. Advances in endoscopic technology
      have brought colonoscopy to the forefront of the management of LGIB. However,
      many questions remained to be answered about its usefulness in routine clinical
      practice. More randomized controlled trials comparing available diagnostic
      strategies for LGIB are needed.

PMID- 16303576
TI  - Lower gastrointestinal bleeding--management.
AB  - Although acute LGIB is only about one fifth as common and is usually less
      hemodynamically significant than upper gastrointestinal bleeding, it presents
      numerous unique clinical challenges. The best diagnostic approach for patients
      with active bleeding is unknown, but urgent prepared colonoscopy is safe and
      likely to be beneficial (Fig. 3, Table 2). In patients who have aggressive
      bleeding or recurrent bleeding, it is critical for the practitioner to judge when
      angiography and surgery are necessary.

PMID- 16303577
TI  - Obscure gastrointestinal bleeding.
AB  - Obscure GI bleeding is a relatively common problem facing internists,
      gastroenterologists, and surgeons in a typical clinical practice. The etiology is
      occasionally suggested by the patient's age, history, and medications. Management
      is complicated and typically requires a team-oriented approach, with input from
      the internist, gastroenterologist, radiologist, and surgeon alike. SBFT and
      enteroclysis seem to have a limited role, unless there is a high suspicion of a
      small bowel mass lesion or Crohn's disease. Scintigraphy may be performed in
      patients with active bleeding in whom endoscopy has failed oris contraindicated.
      Angiography may be used in patients with an early positive nuclear imaging or
      failed endoscopic therapy. Provocative angiography probably has a lower
      diagnostic yield than previously reported, and should be performed only in
      experienced centers. Helical CT is a new and potentially important option in
      patients with obscure bleeding, but is currently considered experimental. All
      patients with obscure GI bleeding should undergo repeat upper endoscopy and
      perhaps colonoscopy to rule out missed lesions. SBE seems to be complementary to
      capsule endoscopy, and it is unknown whether this should be performed before
      capsule endoscopy or only if capsule endoscopy yields a positive proximal small
      bowel finding. Double balloon enteroscopy seems promising, but the technique
      requires further study. Surgery should be reserved for patients who have a
      positive capsule endoscopy requiring surgical therapy or patients who have
      persistent GI bleeding requiring recurrent blood transfusions in whom all other
      modalities have failed. Treatment for vascularectasias, the most common cause of
      obscure GI bleeding, is currently inadequate,and typically requires a combination
      of multiple management approaches.

PMID- 16303579
TI  - Investigation of the small bowel in gastrointestinal bleeding--enteroscopy and
      capsule endoscopy.
AB  - The last frontier in luminal endoscopy has been conquered. Bleeding lesions in
      the small intestine can present a frustrating clinical problem, but recent
      advances have made investigating the small bowel easier and less invasive.
      Capsule endoscopy and double balloon enteroscopy are two new technologies that
      promise to lower the barrier to evaluation of the entire small intestine. Recent
      studies show that capsule endoscopy improves outcomes in patients who have OGIB.
      Although outcome studies regarding double balloon enteroscopy have not been
      performed, the opportunity to treat lesions throughout the small bowel without
      resorting to surgery is a tremendous advance. These improvements suggest that the
      corner may have been turned in the diagnosis and management of small bowel
      bleeding. Perhaps to the next generation of gastroenterologists, small bowel
      bleeding will not be obscure.

PMID- 16303578
TI  - Occult gastrointestinal bleeding.
AB  - Occult gastrointestinal bleeding commonly manifests as iron deficiency anemia or
      fecal occult blood. Iron deficiency anemia results from chronic occult
      gastrointestinal bleeding. Evaluation of asymptomatic patients who have iron
      deficiency anemia or fecal occult blood usually should begin with investigation
      of the colon. Colonoscopy is preferred, but flexible sigmoidoscopy plus air
      contrast barium enema, or computed tomographic colonography may be acceptable in
      certain circumstances. If evaluation of the colon does not reveal a bleeding
      site, evaluation of the upper gastrointestinal tract is mandatory in patients who
      have iron deficiency anemia, and this should be considered in those who have
      fecal occult blood. In patients who have gastrointestinal symptoms, evaluation of
      the portion of the gastrointestinal tract from which the symptoms is derived
      should be pursued initially. The role of small intestinal investigation is
      controversial, and this probably should be reserved for patients who have iron
      deficiency anemia and persistent gastrointestinal symptoms or those who fail to
      respond to appropriate therapy. Celiac sprue should be considered as a potential
      cause of iron deficiency anemia in all patients. The treatment and prognosis of
      patients who have iron deficiency anemia or fecal occult blood depends on the
      gastrointestinal tract abnormality(ies) identified. Those without identifiable
      bleeding sites generally respond to conservative management and have a favorable
      prognosis. On the other hand, the outlook is poorer for patients with refractory
      occult blood loss or those who have vascular ectasias. Both groups of patients
      are clinically challenging and require a focused and experienced team approach to
      diagnosis and therapy.

PMID- 16303580
TI  - Angiographic diagnosis and endovascular management of nonvariceal
      gastrointestinal hemorrhage.
AB  - Diagnostic angiography still plays an essential role in the diagnosis of
      patients,particularly those with acute lower GI bleeding. Transcatheter therapy
      appears to be a viable treatment alternative in selected patients with GI
      bleeding. Many interventionists today believe embolotherapy to be more effective
      initially and to have better long-term results, specifically less rebleeding,
      than vasopressin infusion with at least equal complication rates. Unfortunately,
      direct comparison of the two techniques in a randomized, controlled fashion has
      not been performed. Small patient series, such as those summarized here, suggest
      that the results of the two techniques are essentially equal, and ischemic
      complications appear more prevalent with embolotherapy. The use of embolotherapy-
      either empirically based on endoscopic or surgical findings or directed against a
      site found to have contrast extravasation-represents the current intervention of
      choice in the case of upper GI bleeding refractory to endoscopic intervention.
      Head-to-head studies directly comparing the efficacy, morbidity, and mortality
      associated with endovascular or surgical correction of bleeding from the upper GI
      tract is needed. Although the current tide favors embolotherapy in the lower GI
      tract, infusion of vasoconstricting agents deserves more attention. To that end,
      there is a great need for scientific data regarding the safety and efficacy of
      transcatheter therapy for upper and lower GI bleeding.

PMID- 16303581
TI  - Clinical psychology Ph.D. program rankings: evaluating eminence on faculty
      publications and citations.
AB  - Program rankings and their visibility have taken on greater and greater
      significance. Rarely is the accuracy of these rankings, which are typically based
      on a small subset of university faculty impressions, questioned. This paper
      presents a more comprehensive survey method based on quantifiable measures of
      faculty publications and citations. The most frequently published core clinical
      faculty across 157 APA-approved clinical programs are listed. The implications of
      these data are discussed.

PMID- 16303582
TI  - Comparing descriptive, experimental and informant-based assessments of problem
      behaviors.
AB  - In this study, the outcomes of descriptive, experimental and informant-based
      methods of functional assessment were compared in four individuals with
      developmental disabilities who showed problem behaviors. Results indicated that
      the descriptive and experimental assessments were concordant in only one of the
      four cases whilst informant-based and experimental assessments were concordant in
      three of the four cases. The descriptive assessment identified thin schedules of
      attention in all cases. These results appear to question the usefulness of
      employing descriptive assessments for problem behaviors either as an adjunct or
      replacement for experimental assessments, particularly given their time-consuming
      nature.

PMID- 16303583
TI  - Stereotypy II: a review of neurobiological interpretations and suggestions for an
      integration with behavioral methods.
AB  - Stereotypy is a relatively common behavioral disorder displayed by individuals
      with developmental disabilities, including autism. In this paper, we review
      selected studies on neurobiological interpretations of stereotypy and
      pharmacological interventions for stereotypy. Specifically, we review studies
      that evaluated the effects of serotonin uptake inhibitors (e.g., clomipramine) or
      opioid antagonists (e.g., naltrexone) on stereotypy displayed by humans.
      Throughout, suggestions are made for the incorporation of behavioral methods into
      this area of research.

PMID- 16303584
TI  - Assessment of terms to describe mental retardation.
AB  - There is currently debate among professionals in the area of mental
      retardation/developmental disabilities regarding the use of, and a possible
      replacement for, the term mental retardation. Using the semantic differential
      technique, 284 participants drawn from various Midwestern populations completed
      assessments of several terms used to describe the condition known as mental
      retardation (e.g., intellectual disability) as well as the person with the
      condition (e.g., mentally challenged) and other disabilities (e.g., physically
      disabled). Assessments were made on three factors: evaluation, activity, and
      potency. Results indicated that although all of the terms were generally assessed
      neutrally, the term Mentally Challenged emerged as the most positive particularly
      compared to evaluations of the other investigated terms. Moreover, mentally
      challenged was evaluated as significantly more positive compared to the term
      physically disabled but was similarly evaluated as the term visually disabled.
      Implications of the results are discussed.

PMID- 16303585
TI  - A method for evaluating parameters of reinforcement during parent-child
      interactions.
AB  - We conducted functional analyses and identified reinforcers for problem behavior
      for three individuals with developmental disabilities. Based on results of the
      functional analysis, we evaluated the rate, probability, delay, and duration of
      reinforcement for problem and appropriate behavior during descriptive parent
      child observations. Results showed that parameters of reinforcement, including
      rate, probability, delay, and duration may interact, and that evaluations of a
      single reinforcement parameter may be insufficient in describing response
      allocation. Hence, this study represents a movement toward a method for analyzing
      reinforcer dimensions, other than rate and probability, in a descriptive
      analysis.

PMID- 16303586
TI  - The reliability of the Scale for the Evaluation and Identification of Seizures,
      Epilepsy, and Anticonvulsant Side Effects-B (SEIZES B).
AB  - The use of anti-epileptic medications (AEDs) is much higher in individuals with
      intellectual disabilities than in the general population. As many of these
      individuals rely on such medications, clinicians should consider psychometrically
      sound instruments for assessing adverse side effects of these medications as one
      aspect of routine clinical practice. The Scale for the Evaluation and
      Identification of Seizures, Epilepsy, and Anticonvulsant Side Effects-B (SEIZES
      B) was developed as a means to identify side effects specific to AEDs. The
      authors conducted a preliminary evaluation of the inter-rater and test-retest
      reliability of the SEIZES B on an adult population with developmental
      disabilities. The SEIZES B had moderately high stability across raters and
      adequate stability over time. Implications of these data for future research and
      practice are discussed.

PMID- 16303589
TI  - Neurophysiology of sleep and wakefulness.
AB  - Wakefulness, NREM sleep, and REM sleep are three distinct states of existence.
      Each state has characteristic behavioral and physiologic patterns,and each has
      specific neurophysiologic mechanisms associated with its generation and control.
      Structures in the brainstem use various neurotransmitters to influence higher
      brain structures in the midbrain and cortex. The ARAS provides cholinergic,
      noradrenergic, and glutaminergic stimulation to the thalamus, hypothalamus, and
      basal forebrain resulting in cholinergic and glutaminergic excitation of the
      cortex. An active cortex that exhibits a characteristic pattern of desynchronized
      EEG manifests wakefulness. Various factors affect the need and timing of sleep
      onset. These factors influence the nucleus tractus solitarius, causing its
      noradrenergic projections to midbrain and forebrain structures to inhibit
      activity in the ARAS, resulting inactivation of inhibitory GABAergic
      thalamocortical projections to the cor-tex. During a state of decreased
      activation, the cortex exhibits a pattern of synchronized EEG. Transition between
      NREM sleep and REM sleep is controlled by noradrenergic neurons in the loci
      coeruleus and serotoninergic neurons in the raphe called REM-off cells and
      cholinergic neurons in the nucleus reticularis pontis oralis called REM-on cells.
      Other brain structures are involved in generation and control of REM sleep
      related phenomena, such as eye movement and muscle atonia. During wakefulness,
      there is increased sympathetic tone and decreased parasympathetic tone that
      maintains most organ systems in a state of action or readiness. During NREM
      sleep, there is decreased sympathetic tone and increased parasympathetic activity
      that creates a state of reduced activity. REM sleep is characterized by increased
      parasympathetic activity and variable sympathetic activity associated with
      increased activation of certain brain functions. The states of wakefulness and
      sleep are characterized as stages that are defined by stereotypical EEG, EMG, and
      EOG patterns. Wakefulness stage has an EEG pattern predominated by the alpha
      rhythm. With onset of stage 1 sleep, the alpha rhythm attenuates, and an EEG
      pattern of relatively low voltage and mixed frequency is seen. Progression to
      stage 2 sleep is defined by the appearance of sleep spindles or K-complexes.
      Further progression into the deepest sleep stages 3 and 4 is defined by the
      occurrence of high-amplitude, low-frequency EEG activity. The progression of
      sleep stages occurs in cycles of 60 to 120 minutes throughout the sleep period.
      Various circadian environmental and ontologic factors affect the pattern of sleep
      stage occurrence.

PMID- 16303590
TI  - Basic principles of polysomnography including electrical concepts.
AB  - Polysomnographic technology has advanced by exponential degrees since the first
      sleep studies were conducted by Dement. The basic electrical concepts have
      remained the same since that time and are an essential element in the
      understanding of polysomnographic equipment. The application of these basic
      electrical concepts has allowed, however, for an improvement in the
      acquisition,manipulation, and storage of physiologic data during sleep. This
      article defines polysomnography in terms of its history and its current status.
      The basic electrical concepts are presented with their application to
      polysomnography. A discussion of other basic principles is included with
      practical application.

PMID- 16303591
TI  - Clinical assessment of the sleep disordered patient.
AB  - Daytime sleepiness and inadequate sleep patterns have become a universal issue.
      The effects of sleep loss are more than just a nuisance; sleep loss can lead to
      increased mortality. Prudent and responsible clinicians should make the sleep
      assessment a routine part of the health history.

PMID- 16303592
TI  - Instrumentation and electrode placement.
AB  - The field of sleep diagnostics and polysomnography has increased significantly in
      the past 2 decades, and the need for expertly trained and qualified technologists
      has never been greater. This article instructs the therapist in the importance of
      proper patient hookup, reviews the 10-20 international system of electrode
      placement, considers accurate placement of electrodes and sensors, and discusses
      the use of various instrumentation.

PMID- 16303593
TI  - Troubleshooting and elimination of artifact in polysomnography.
AB  - A sleep technician who runs a sleep study without understanding the basis of the
      signals being acquired can spend a lot of time and energy trying to improve poor
      signal quality without success. Poor signal quality often results in an image
      that cannot be interpreted or is difficult to interpret, and extensive
      troubleshooting often results in a very disrupted sleep study. This article
      addresses trouble-shooting and elimination of artifact in polysomnography.

PMID- 16303594
TI  - Cardiac arrhythmias.
AB  - This article presents an overview of common cardiac arrhythmias. Interventions
      for severe and potentially severe arrhythmias are discussed. Tips for recording
      and viewing the electrocardiogram as employed in polysomnography are presented.
      The focus is on arrhythmias, and as such the information revolves around rhythm,
      rate, and blocks. The reader is referred to other sources for discussion of
      topics such as axis, ischemia, and infarct.

PMID- 16303595
TI  - Monitoring respiration during sleep.
AB  - Monitoring of respiration during sleep allows the assessment of physiologic
      variables that are required to characterize SRBD events. The patency of the upper
      airway, the pattern of breathing, oxygenation, and ventilation usually can be
      inferred from simultaneous measurements of airflow, respiratory effort, thoracic
      volume, and blood gases. As new techniques of respiratory monitoring emerge, the
      respiratory therapist and sleep technologist must be familiar with the advantages
      and shortcomings of each modality.

PMID- 16303596
TI  - Positive airway pressure and oxygen therapy in the sleep laboratory.
AB  - Adequate titration of PAP and oxygen therapy depends on intuitive, observant, and
      highly skilled acquisition technicians. Sleep laboratories must have a variety of
      equipment to ensure that technicians have adequate resources during manual
      titrations. Titration policies and procedures must be determined and written by
      sleep laboratory staff to ensure compliance with third-party payers, provide
      guidance to technical staff, and enable ongoing quality improvement processes.
      Methods of PAP and NIPPV are discussed.

PMID- 16303597
TI  - Sleep stage scoring in the adult population.
AB  - Sleep stage scoring is a system-based classification procedure requiring
      knowledge and understanding of brainwave electrical potentials and their patterns
      in different cortical areas. Monitoring precise scalp locations requires
      standardized electrode placements. The electroencephalogram is recorded
      concurrently with eye movement potentials (electro-oculogram) and submentalis
      muscle activity (electromyogram). The resulting recording is a polysomnogram.
      This article addresses sleep stage scoring in adults.

PMID- 16303598
TI  - Event scoring in polysomnography: scoring arousals, respiratory events, and leg
      movements.
AB  - Polysomnographic events comprise a wide variety of phenomena,including episodes
      of apnea, episodes of hypopnea, leg movements, transient central nervous system
      arousals, and eye movements. The process of event scoring involves pattern
      recognition and provides a description of potentially pathophysiologic activity
      occurring during sleep. The rules for scoring sleep-related events continue to be
      developed. The rules are precise and must be followed with extreme care. When the
      polysomnogram is interpreted,the report must include a summary of event scoring
      and clinical correlation to the sleep complaint. Arousals, periodic limb
      movements, and respiratory events are significant because they represent
      pathophysiologies on which final diagnosis largely depends.

PMID- 16303599
TI  - Antimitogenic effects of prostacyclin on the G1 phase cyclin-dependent kinases.
AB  - The prostanoid prostacyclin (PGI2) inhibits proliferation of cultured vascular
      SMCs by inhibiting cell cycle progression from G1 to S phase. Progression through
      G1 phase is regulated by the sequential activation of the G1 phase cyclin
      dependent kinases (cdks). Recent studies have shown that PGI2-dependent
      activation of its receptor, IP, inhibits G1 phase progression by blocking the
      degradation of p27 and the activation of cyclin E-cdk2. High Density Lipoproteins
      (HDL) and its associated apolipoprotein, ApoE, also inhibit S phase entry of
      vascular SMCs, and the effects of HDL and ApoE are, at least in part, also
      mediated by the production of PGI2. The antimitogenic effects of hyaluronan may
      also be controlled by PGI2. This review summarizes the effects of PGI2 on the G1
      phase cyclin-cdks and discusses the potential role of PGI2 as a common component
      of multiple extracellular signals that attenuate the proliferation of vascular
      SMCs.

PMID- 16303600
TI  - Nomenclature systems for the neuroprostanes and for the neurofurans.
AB  - The isolation of two new classes of human docosahexaenoic acid oxidation
      products, the neuroprostanes and the neurofurans, have been reported. Facile
      nomenclature systems that will allow the rational differentiation of each of the
      isomeric structures comprising the families of NeuroP's and NeuroF's,
      represented, respectively, by 17-F(4t)-NeuroP 1 and 10-epi-ST-Delta(15)-11-NeuroF
      2 are presented.

PMID- 16303601
TI  - Effect of deletion of the prostaglandin EP4 receptor on stimulation of calcium
      release from cultured mouse calvariae: impaired responsiveness in heterozygotes.
AB  - The ability of prostaglandin E2 (PGE2), selective receptor agonists for EP2 and
      EP4 receptors (EP2A and EP4A) and parathyroid hormone (PTH) to stimulate calcium
      release from cultured fetal mouse calvariae was compared in wild type (WT) mice
      and in mice heterozygous (HET) or homozygous (KO) for deletion of the EP4
      receptor. Calvariae from 19 day fetal mice were used in order to avoid the
      problem of high neonatal mortality. Calcium release was increased by PGE2, EP4A
      or PTH in WT mice, but EP2A had no significant effect. There was a significant
      decrease in calcium release in response to PGE2, EP4A and PTH in calvariae from
      HET mice compared to WT mice. The response to PGE2 and EP4A was abrogated and the
      response to PTH was further diminished in EP4 receptor KO mice. These results
      suggest that the EP4 receptor may be rate limiting not only for PGE2 stimulated
      resorption but also for resorption stimulated by other agonists, like PTH that
      induce PGE2 production.

PMID- 16303602
TI  - Molecular cloning and tissue distribution of microsomal-1 and cytosolic
      prostaglandin E synthases in macaque.
AB  - Prostaglandins derived from arachidonic acid are involved in a wide variety of
      physiological and pathological processes. The primary enzymes involved in the
      production of PGE2 from arachidonic acid are cyclooxygenases and prostaglandin E
      synthases. These enzymes have been identified in human, but only partially in the
      monkey where microsomal PGES-1 and cytosolic PGES have not been characterized.
      The present study was undertaken to clone these enzymes and to study their tissue
      distribution, along with mPGES-2. The coding sequence of Macaque mPGES-1 is 98%
      homologous to human mPGES-1 at the nucleic acid level and the deduced amino acid
      sequence has 98% homology with the human protein. The Macaque cPGES cDNA is more
      than 99% homologous to the human and the deduced amino acids sequence is
      identical to that of the human cPGES. By Northern blot analysis, we found that
      mPGES-2 and cPGES mRNA were expressed in the endometrium, myometrium, ovary and
      oviduct, albeit at different levels, while mPGES-1 mRNA was detected at a weak
      level, mainly in the oviduct. Western Blot analysis revealed that mPGES-2, mPGES
      1 and cPGES proteins were present in all tissues tested. These results suggest
      that production of PGE2 in Macaque may involve more than one PGES and that
      further studies will be needed to fully understand the conditions under which
      each PGES contributes to PGE2 production.

PMID- 16303603
TI  - Influence of a prostaglandin synthesis inhibitor administered at embryo transfer
      on pregnancy rates of recipient cows.
AB  - Elevated uterine luminal concentrations of prostaglandin F(2alpha) (PGF(2alpha))
      have been negatively associated with embryo quality and pregnancy rates. Two
      studies were performed in cows to determine PGF(2alpha) release from uterine
      endometrium following embryo transfer and to investigate administration of
      flunixin meglumine (FM), a prostaglandin synthesis inhibitor, on pregnancy rates
      following embryo transfer. In Experiment 1, blood samples were collected prior to
      and after embryo transfer from the posterior vena cava via saphenous vein
      cannulation. Serum profiles of PGF(2alpha) indicated that manipulation of the
      reproductive tract during embryo transfer was followed by increased release of
      PGF(2alpha) from the uterine endometrium. In Experiment 2, estrus (day=0) was
      synchronized in recipient animals and a single embryo transferred 7 days after
      estrus. At the time of non-surgical embryo transfer, animals were randomly
      assigned to receive either FM (FM; n=1300) or remain untreated (control (CON);
      n=797). Data collected at transfer included stage of embryo development, embryo
      quality, technician, and transfer quality score. Overall pregnancy rates of cows
      receiving FM (65%) were higher than control cows (60%; P<0.02). Pregnancy rates
      following transfer of quality 1 (good) embryos did not differ (P>0.05) between
      treatments. However, pregnancy rates of quality 2 (fair) embryos were higher in
      animals receiving FM than in CON (P<0.01). Moreover, pregnancy rates of
      transferred morula- and blastocyst-stage embryos were higher in FM-treated than
      in controls (P<0.06 and P<0.04, respectively). In conclusion, uterine release of
      PGF(2alpha) is elevated following embryo transfer and administration of a
      PGF(2alpha) synthesis inhibitor at the time of embryo transfer improved pregnancy
      rates in cows.

PMID- 16303604
TI  - Effect of peroxisome proliferator-activated receptor-gamma ligands on the
      expression of retinoic acid-inducible gene-I in endothelial cells stimulated with
      lipopolysaccharide.
AB  - Retinoic acid-inducible gene-I (RIG-I) is a member of the DExH box protein family
      and designated as a putative RNA helicase. RIG-I is implicated in host defense
      and inflammatory reactions by regulating the expression of various genes. RIG-I
      is expressed in endothelial cells and upregulated with lipopolysaccharide (LPS).
      Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear
      hormone receptor and regulates gene expressions in response to its specific
      ligands. In the present study, we examined the effect of PPAR-gamma ligands on
      the LPS-induced RIG-I expression in cultured human umbilical vein endothelial
      cells (HUVEC). 15-Deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2), a metabolite of
      PGD2, is a natural ligand for PPAR-gamma and known to modulate inflammatory
      reactions by regulating the expression of various genes in PPAR-gamma-dependent
      and -independent manners. LPS-induced RIG-I expression in HUVEC was inhibited by
      pretreatment of the cells with 15d-PGJ2 in time-and concentration-dependent
      manners. However, ciglitazone and bisphenol A diglycide ether, authentic and
      specific ligands for PPAR-gamma, did not affect the RIG-I expression. These
      results suggest that 15d-PGJ2 inhibits LPS-induced RIG-I expression through a
      mechanism independent on PPAR-gamma. 15d-PGJ2 may regulate inflammatory
      reactions, at least in part, by inhibiting the expression of RIG-I.

PMID- 16303605
TI  - Group IV cytosolic phospholipase A2 mediates arachidonic acid release in H9c2 rat
      cardiomyocyte cells in response to hydrogen peroxide.
AB  - Damaging reactive oxygen species are released during episodes of ischemia and
      reperfusion. Some cellular adaptive responses are triggered to protect the
      injured organ, while other cascades are triggered which potentiate the damage. In
      these studies, we demonstrate that rat cardiomyocte H9c2 cells release
      arachidonic acid in response to hydrogen peroxide. In H9c2 cells, arachidonic
      acid release is attenuated by methyl arachidonyl fluorophosphonate (MAFP) and
      pyrrophenone, indicating that a phospholipase A2 Group IV enzyme mediates
      arachidonic acid mobilization. Moreover, hydrogen peroxide alters the cellular
      morphology of the H9c2 cells, causing drastic cell shrinkage. Because MAFP and
      pyrrophenone prevent the morphological alterations caused by hydrogen peroxide,
      these studies show that phospholipase A2 Group IV activity is likely integrally
      involved in the damage initiated by hydrogen peroxide.

PMID- 16303606
TI  - Effect of progesterone on the expression of bax and bcl-2 and on caspase activity
      in bovine luteal cells.
AB  - Bovine luteal cells from days 6-10 and 11-15 of the estrous cycle were exposed (6
      h) to factors that support or disrupt steroidogenesis. The expression of bcl-2
      and bax and level of active caspase-3 in cells was measured. Progesterone (P4)
      increased (P<0.01) while staurosporine decreased (P<0.01-P<0.001) bcl-2
      expression at both stages of the estrous cycle studied. In cells from 11-15 days
      of the estrous cycle expression of bcl-2 was stimulated (P<0.05) by prostaglandin
      (PG)E2 and inhibited (P<0.01) by 3,3',4,4'-tertrachlorobiphenyl (PCB)-77.
      Treatment with aminoglutethimide (blocker of cytochrome P450scc; 1.5 x 10(-4)M),
      nitric oxide donor (spermine NONOate), and staurosporine increased bax expression
      in cells collected from both experimental periods. The influence of these factors
      was greater in cells from days 11-15 (P<0.001) than by cells on days 6-10
      (P<0.05) of the estrous cycle. PCB-77 stimulated expression of bax in cells from
      11-15 days of cycle (P<0.01) only. Treatment of luteal cells with P4 and PGE2 for
      24 h decreased (P<0.05) level of active caspase-3 while aminoglutethimide
      (P<0.05), spermine NONOate (P<0.05), and staurosporine (P<0.001) increased
      caspase-3 activity in the cells. Moreover, P4 decreased (P<0.05) while
      staurosporine increased (P<0.01) the ratio of bax/bcl-2 at both stages of the
      cycle. Aminoglutethimide, spermine NONOate and PCB increased (0<0.05) this ratio
      in cells on days 11-15 of the cycle. These results suggest that P4 concentrations
      in luteal cells protects against apoptosis, while disruption of steroidogenesis
      and reduced ability of luteal cells to produce P4 can induce cell death.

PMID- 16303607
TI  - Effects of BM-573, a thromboxane A2 modulator on systemic hemodynamics
      perturbations induced by U-46619 in the pig.
AB  - The aim of our study was to evaluate the effects of thromboxane A2 (TXA2)
      agonist, U-46619, on systemic circulatory parameters in the pigs before and after
      administration of a novel TXA2 receptor antagonist and synthase inhibitor (BM
      573). Twelve anesthetized pigs were randomly assigned in two groups: in Ago group
      (n=6), the animals received six consecutive injections of U-46619 at 30 min
      interval, while in Anta group (n=6) they received an increasing dosage regimen of
      BM-573 10 min before each U-46619 injection. The effects of each dose of BM-573
      on ex vivo platelet aggregation induced by arachidonic acid, collagen or ADP were
      also evaluated. Vascular properties such as characteristic impedance, peripheral
      resistance, compliance, arterial elastance were estimated using a windkessel
      model. Intravenous injections of 0.500 mg/ml of BM-573 and higher doses resulted
      in a complete inhibition of platelet aggregation induced by arachidonic acid. In
      the same conditions, BM-573 completely blocked the increase of arterial
      elastance, and stabilized both mean aortic blood pressure and mean systemic blood
      flow. In conclusion, BM-573 could therefore be a promising therapeutic approach
      in pathophysiological states where TXA2 plays a main role in the increase of
      vascular resistance like in pathologies such as systemic hypertension.

PMID- 16303608
TI  - Urinary 8-isoprostaglandin F(2alpha) level in Behcet's disease.
AB  - Although its etiology remains unknown, the increased production of reactive
      oxygen species in Behcet's disease (BD) have been reported. Furthermore, it has
      been suggested that vascular and endothelial tissue damage seen in BD is related
      to elevated reactive oxygen species generated by activated neutrophils from BD
      patients. To investigate the formation of lipid peroxidation in BD patients in
      vivo, urinary level of 8-isoprostaglandin F(2alpha) was quantitated by enzyme
      immunoassay after solid phase extraction in different clinical forms of BD
      patients. There was no difference in urinary level of 8-isoprostaglandin
      F(2alpha) between BD patient and healthy control group. There was also no
      difference in urinary levels of 8-isoprostaglandin F(2alpha) in subgroup analyses
      of BD patients, i.e. in mucocutaneous and vascular type BD patients; active and
      inactive BD patients. Contrary to the findings in literature, we found no
      difference in urinary level of 8-isoprostaglandin F(2alpha) between patients with
      systemic lupus erythematosus and healthy control group. These findings show no
      increase in lipid peroxidation despite the augmented formation of reactive oxygen
      species in BD patients. It may be interesting to assess formation of urinary
      level of 8-isoprostaglandin F(2alpha) in BD patients who do not take any
      medication.

PMID- 16303609
TI  - Rainbow trout (Oncorhynchus mykiss) brain cells biosynthesize novel
      docosahexaenoic acid-derived resolvins and protectins-Mediator lipidomic
      analysis.
AB  - Docosahexaenoic acid (DHA; C22:6 n-3) is an abundant fatty acid in fish
      phospholipids. In the present study, we employed liquid chromatography
      ultraviolet spectrometry-tandem mass spectrometry and dissociated rainbow trout
      (Oncorhynchus mykiss) brain cells to determine whether fish utilize endogenous
      DHA to produce the recently uncovered novel lipid mediators termed the resolvins
      and protectins, generated by mammalian cells [Serhan CN, Hong S, Gronert K, et
      al. Resolvins: a family of bioactive products of omega-3 fatty acid
      transformation circuits initiated by aspirin treatment that counter
      proinflammation signals. J Exp Med 2002; 196:1025-37; Hong S, Gronert K, Devchand
      P, Moussignac R-L, Serhan, CN. Novel docosatrienes and 17S-resolvins generated
      from docosahexaenoic acid in murine brain, human blood, and glial cells. J Biol
      Chem 2003;278:14677-87]. Trout brain cells biosynthesize a range of recently
      identified di- and tri-hydroxy-containing bioactive products from endogenous
      sources of DHA when challenged in vitro. We identified neuroprotectin D1,
      resolvin D5, resolvin D1 and resolvin D2 from trout brain cells. Each compound
      was identified on the basis of its characteristic physical chemical properties
      that included MS, MS-MS, UV spectra and chromatographic behavior. The monohydroxy
      products from DHA, signatures of DHA conversion by lipoxygenases, were also
      identified. These included both 14S-hydroxy-docosahexaenoic acid and 17S-hydroxy
      docosahexaenoic acid. The biosynthesis of these novel bioactive lipid mediators,
      namely resolvins and protectins, by fish cells provides the first evidence for
      the conservation of these structures from fish to humans as chemical signals in
      diverse biological systems.

PMID- 16303610
TI  - In vivo reopening of the neonatal ductus arteriosus by a prostanoid EP4-receptor
      agonist in the rat.
AB  - Prostaglandin E1 is used to reopen the constricted ductus arteriosus in neonates
      with ductus-dependent circulation. To clarify possible prostanoid receptor
      agonists that can reopen the neonatal ductus with fewer side effects, we studied
      in vivo reopening of the neonatal ductus arteriosus by AE1-329, a prostanoid EP4
      receptor agonist, in the rat. Neonatal rats were incubated at 33 degrees C. The
      inner diameter of the ductus was measured with a microscope and a micrometer
      following rapid whole-body freezing. Intraesophageal pressure was measured with a
      Millar micro-tip transducer. The ductus arteriosus constricted quickly after
      birth, and the inner diameter was 0.80 and 0.08 mm at 0 and 60 min after birth.
      PGE1 and AE1-329, injected subcutaneously at 60 min after birth, dilated the
      ductus dose-dependently. Thirty minutes after injection of 10 ng/g of PGE1 and
      AE1-329, the ductus diameter was 0.52 and 0.65 mm, respectively. The ductus
      dilating effect of PGE1 was maximal at 15-30 min, and disappeared at 2 h. The
      ductus-dilating effect of AE1-329 was prolonged, the ductus was widely open at 6
      h, and closed at 12 h after injection of 10 ng/g AE1-329. AE1-259-01 (EP2
      agonist) (100 ng/g) did not dilate the neonatal ductus. Respiration was depressed
      by PGE1, but not by AE1-329. These results indicate the major role of EP4 in the
      neonatal ductus and that AE1-329, an EP4 agonist, can be used to dilate the
      neonatal constricted ductus without the side effects shown by EP3, including
      apnea.

PMID- 16303611
TI  - Is nitric oxide luteolytic or antiluteolytic?
AB  - Nitric oxide (NO) has been reported to be luteolytic based on treatment of cows
      in vivo with an inhibitor of nitric oxide synthase (NOS-produces NO), which
      delayed the decline in progesterone by two to three days [Jaroszewki J, Hansel,
      W. Intraluteal administration of a nitric oxide synthase blocker stimulates
      progesterone, oxytocin secretion and prolongs the life span of the bovine corpus
      luteum. Proc Soc Exptl Biol Med 2000;224:50-5; Skarzynski D, Jaroszewki J, Bah,
      M, et al. Administration of nitric oxide synthase inhibitor counteracts
      prostaglandin F(2alpha)-induced luteolysis in cattle. Biol Reprod 2003;68:1674
      81]. The objective of this experiment was to determine the effect of a long
      acting NO donor or a NOS inhibitor infused chronically into the interstitial
      tissue of the ovarian vascular pedicle adjacent to the ovary with a corpus luteum
      on secretion of progesterone during the ovine estrous cycle. Ewes were treated
      either with Vehicle (N=5); Diethylenetriamine (DETA-control for DETA-NONOate;
      N=5); (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl) amino]diazen-1-ium-1,2-diolate
      (DETA-NONOate-long acting NO donor; N=6); or l-nitro-arginine methyl ester (l
      NAME-NOS inhibitor; N=6) every 6 h from 24:00 h (0 h) on day 8 through 18:00 h on
      day 18 of the estrous cycle. Jugular venous blood was collected every 6h for
      analysis for progesterone and corpora lutea were collected at 18:00 h on day 18
      and weighed. Weights of corpora lutea were heavier (P< or =0.05) in DETA-NONOate
      treated ewes when compared to Vehicle, DETA, or l-NAME-treated ewes, which did
      not differ amongst each other (P> or =0.05). Profiles of progesterone in jugular
      venous blood on days 8-18 differed (P< or =0.05) in DETA-NONOate-treated ewes
      when compared to Vehicle, DETA, or l-NAME-treated ewes did not differ (P> or
      =0.05) amongst each other. It is concluded that NO is not luteolytic during the
      ovine estrous cycle, but may instead be antiluteolytic and prevent luteolysis.

PMID- 16303612
TI  - Maternal and feto-placental prostanoid responses to a single course of antenatal
      betamethasone.
AB  - We tested the hypothesis that antenatal betamethasone alters prostanoid levels in
      the maternal and feto-placental compartments. Forty-three singleton pregnancies
      were studied. Group I were women treated with a single course of antenatal
      betamethasone and who delivered <37 weeks gestation; Group II were untreated
      women who delivered <37 weeks; and Group III were untreated women who delivered
      >38 weeks. Maternal and mixed cord blood; and placental samples were collected at
      delivery and analyzed for PGE2, PGF(2alpha), 6-ketoPGF(1alpha), and TxB2 levels.
      Antenatal betamethasone decreased maternal PGE2 levels with concomitant increases
      in the feto-placental compartment. Umbilical cord TxB2 levels in the treated
      group were significantly lower than the non-treated pre-term and term groups
      resulting in a higher 6-ketoPGF(1alpha):TxB2 ratio. Considering the regulatory
      role of PGE2 and PGI2 in fetal lung development and neonatal transition
      homeostasis, these results suggest a mechanism, at least in part, for the
      beneficial effects of antenatal steroids on fetal lung maturation and neonatal
      cardio-pulmonary homeostasis at birth.

PMID- 16303613
TI  - Transforming growth factor beta1 and prostaglandin E2 concentrations are
      associated with bone formation markers in ulcerative colitis patients.
AB  - Osteoporosis is a significant complication of a multifactoral etiology associated
      with inflammatory bowel disease. The aim of study was to evaluate the
      relationships between bone mineral density as well as bone turnover markers and
      inflammatory activity modulators (i.e., PGE2 and TGFbeta1) in ulcerative colitis
      (UC). Twenty-one active ulcerative colitis subjects and 14 healthy individuals
      were included into the study. We observed no significant differences in serum
      concentrations of osteoprotegerin and osteocalcin, as well as bone mineral
      density between UC patients and healthy individuals. Plasma concentrations of
      PGE2, TGFbeta1 and TNF-alpha were significantly higher in UC patients than in
      controls. Serum osteocalcin demonstrated a positive correlation with both serum
      PGE2 and plasma TGFbeta1. Moreover there was significant correlation between
      osteoprotegerin and TGFbeta1 as well as serum TNF-alpha concentrations. In
      conclusion a positive association between PGE2 and TGFbeta1 and bone formation
      markers-osteoprotegerin and osteocalcin, as well as a comparable BMD in UC
      patients and healthy individuals was shown. Our results may indicate that
      increase of PGE2 as well as TGFbeta1 concentrations may play a protective role
      against bone loss in ulcerative colitis patients.

PMID- 16303614
TI  - Stimulatory effect of LH, PGE2 and progesterone on StAR protein, cytochrome P450
      cholesterol side chain cleavage and 3beta hydroxysteroid dehydrogenase gene
      expression in bovine luteal cells.
AB  - The aim of these studies was to investigate the effect of LH, progesterone (P4),
      PGE, noradrenaline (NA) and a nitric oxide donor, S-nitroso-N-acetylpenicillamine
      (S-NAP), on steroid acute regulatory protein (StAR), 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD) and cytochrome P450 side chain cleavage (P450scc) gene
      expression and on the synthesis of their protein products. Bovine luteal cells
      were collected and prepared on days 6-10 of the estrous cycle and preincubated in
      vitro for 24 h. Thereafter, medium was changed and supplemented with one of six
      treatments: control medium, LH (100 ng/ml), P4 (10(-5)M), PGE2 (10(-6)M), NA (10(
      5)M) or S-NAP (10(-4)M). In Experiment 1, luteal cells (10(6)/well) were
      incubated for 3, 6, 18 and 24 h. After incubation, total RNA was isolated and P4
      concentrations in medium was determined. Semiquantitative RT-PCR was used to
      measure gene expression. In Experiment 2, luteal cells were preincubated for 24h,
      then stimulated as in Experiment 1. Total protein was isolated from lysed cells
      and Western blot analysis was performed using specific antibodies against the
      StAR, 3beta-HSD and cytochrome P450scc proteins. Bands were analyzed by means of
      KODAK 1D Image Analysis Software. In Experiment 1, LH and PGE2 stimulated
      secretion of progesterone from luteal cells. Concentrations of mRNA for StAR,
      3beta-HSD, cytochrome P450scc were increased after 6 h in cells stimulated with
      LH, PGE2 and P4 (P<0.05). Gene expression was not affected by NA. In Experiment
      2, LH, P4 and PGE2 induced an increase in the concentration of these three
      proteins. S-NAP inhibited both concentrations of mRNA and protein for StAR, 3beta
      HSD, cytochrome P450scc. Therefore, the increase in secretion of P4 induced by LH
      and PGE2 is associated with increases in StAR, 3beta-HSD and cytochrome P450scc
      gene expression. This genomic response may be mediated in part through a positive
      effect of P4 on the expression of these genes observed in this experiment.

PMID- 16303615
TI  - 12/15-Lipoxygenase gene disruption and vitamin E administration diminish
      atherosclerosis and oxidative stress in apolipoprotein E deficient mice through a
      final common pathway.
AB  - Studies in mouse models of atherosclerosis using 12/15-lipoxygenase (12/15-LO)
      gene disruption and transgenic overexpression demonstrate a pro-oxidative, pro
      atherogenic role for this pathway. Vitamin E has been shown to suppress lipid
      peroxidation and reduce early atherogenesis in several mouse models, although
      conflicting results from several clinical trials have been reported. ApoE(-/-)
      and apoE(-/-)/12/15-LO(-/-) mice were maintained on normal chow diet with or
      without Vitamin E supplement (2000 IU/kg). Plasma Vitamin E, urinary 8,12-iso
      iPF(2alpha)-VI and aortic lesion quantitation were assessed. Plasma Vitamin E
      levels significantly increased upon Vitamin E diet supplementation. 12/15-LO gene
      disruption resulted in significantly reduced aortic lesions and decreased urinary
      8,12-iso-iPF(2alpha)-VI levels in apoE(-/-) mice, similar to Vitamin E
      administration in the absence of 12/15-LO gene disruption. However, Vitamin E
      dietary supplementation did not afford additive or synergistic protection in
      apoE(-/-)/12/15-LO(-/-) mice. These results suggest that early 12/15-LO-mediated
      lipid peroxidation triggers ensuing non-enzymatic peroxidation that is
      susceptible to Vitamin E antioxidant action in a common pathway of atherogenesis.

PMID- 16303616
TI  - Captopril effect on prostaglandin E2, thromboxane B2 and proteinuria in lupus
      nephritis patients.
AB  - OBJECTIVE: High urinary Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) levels
      have been reported in lupus nephritis (LN). Captopril diminishes proteinuria and
      improves glomerular filtration rate (GFR), and may have effect on immune
      function. We evaluate captopril effect on urinary PGE2, and TxB2. METHODS:
      Eighteen LN patients were randomly assigned to two groups. Group 1 received only
      prednisone plus cyclophosphamide. Group 2 received also captopril. Serum
      creatinine, GFR, RPF, urinary proteins, PGE2 and TxB2, were assessed. RESULTS:
      There were no differences between the initial and final assessments in Group 1.
      Group 2 showed a significant decrement in proteinuria (p=0.003) and serum
      creatinine (p=0.01) at the end of the study. PGE2 decreased significantly when
      compared with the initial value (p=0.02). CONCLUSION: Captopril plus usual
      treatment, improved serum creatinine and decreased proteinuria in parallel with
      prostaglandin E2 reduction. This effect is not related to changes in GFR or RPF.
      Captopril may have an immunomodulatory effect on local inflammatory processes in
      lupus nephritis.

PMID- 16303617
TI  - Phytoestrogen metabolites are much more active than phytoestrogens themselves in
      increasing prostaglandin F(2alpha) synthesis via prostaglanin F(2alpha) synthase
      like 2 stimulation in bovine endometrium.
AB  - Phytoestrogens have recently been suggested to be the cause of infertility by
      stimulating luteolytic prostaglandin (PG) F(2alpha) secretion from endometrium in
      cattle. The purpose of this study was to examine the enzymatic and molecular
      mechanisms involved in the preferential induction of PGF(2alpha) synthesis by
      phytoestrogens, and whether phytoestrogens influence endometrial cell viability.
      Cultured bovine endometrial epithelial and stromal cells were exposed to
      phytoestrogens (daidzein and genistein) and their metabolites (equol and p-ethyl
      phenol) for 24h. Prostaglandin F(2alpha) and PGE2 were stimulated by
      phytoestrogens in both stromal and epithelial cells, with a preference for
      PGF(2alpha) synthesis in epithelial cells (P<0.001). Although RT-PCR and Western
      Blot analyses did not reveal the influence of phytoestrogens on either gene
      expression or protein level of cyclooxygenase-2 (COX-2) and PGE2 synthase (PGES)
      in stromal and epithelial cells (P>0.05), the stimulative effects of equol and p
      ethyl phenol on PGF(2alpha) synthase-like 2 (PGFSL2) gene expression and protein
      level were observed only in epithelial cells (P<0.05). The same compounds did not
      affect PGFSL2 gene expression and protein in stromal cells (P>0.05). Exposure to
      phytoestrogens and their metabolites decreased cell viability in both stromal and
      epithelial cells. Stromal cell viability decreased to 50% of the control and was
      more evident than that in epithelial cells (P<0.001). The overall results suggest
      that infertility in cattle, caused by phytoestrogen-dependent preferential
      stimulation of luteolytic PGF(2alpha) synthesis, is caused by increasing PGFSL2
      in epithelial cells, and by decreasing stromal cell viability, which are the main
      source of luteotropic PGE2 production.

PMID- 16303618
TI  - Involvement of platelet-activating factor and leukotrienes in anaphylactic
      segmental venoconstriction in ovalbumin sensitized guinea pig livers.
AB  - The hepatic anaphylactic venoconstriction is partly involved in anaphylactic
      hypotension, and is characterized by significant post-sinusoidal constriction and
      liver congestion in guinea pigs. We determined what chemical mediators are
      involved in anaphylaxis-induced segmental venoconstriction and liver congestion
      in perfused livers isolated from ovalbumin sensitized guinea pigs. Livers were
      perfused portally and recirculatingly at constant flow with diluted blood. The
      sinusoidal pressure was measured by the double occlusion pressure (Pdo), and was
      used to determine the pre-sinusoidal (Rpre) and post-sinusoidal (Rpost)
      resistances. An antigen injection increased both the portal vein pressure and
      Pdo, resulting in 4.1- and 2.3-fold increases in Rpre and Rpost, respectively.
      Hepatic congestion was observed as reflected by liver weight gain. Pretreatment
      with TCV-309 (10microM, platelet-activating factor (PAF) receptor antagonist) or
      ONO-1078 (100microM, human cysteinyl-leukotriene (Cys-LT) receptor 1 antagonist),
      but not indomethacin (10microM, cyclooxygenase inhibitor), ketanserin (10microM,
      serotonin receptor antagonist), or diphenhydramine (100microM, histamine H1
      antagonist), significantly attenuated this anaphylactic hepatic venoconstriction.
      Anaphylaxis-induced increases in Rpre and Rpost were significantly inhibited by
      TCV-309 (by 48%) and ONO-1078 (by 36%), respectively. Combined TCV-309 and ONO
      1078 pretreatment exerted additive inhibitory effects on anaphylactic hepatic
      venoconstriction. Anaphylactic hepatic weight gain was converted to weight loss
      when post-sinusoidal constriction was attenuated. It is concluded that
      anaphylaxis-induced pre-sinusoidal constriction is mainly caused by PAF and the
      post-sinusoidal constriction by Cys-LTs in guinea pig livers.

PMID- 16303619
TI  - Long-term intake of edible oils benefits blood pressure and myocardial structure
      in spontaneously hypertensive rat (SHR) and streptozotocin diabetic SHR.
AB  - The beneficial effects of edible oils long-term supplementation in blood pressure
      (BP) and cardiac structure were investigated in spontaneously hypertensive rat
      (SHR) and streptozotocin diabetic (Db) SHR (45 mg/rat i.p.). Twenty-five 12-week
      old male SHR were divided into four SHR-Db groups and one SHR group, SHR-Db
      groups each receiving, respectively, olive oil, palm oil and fish oil, and
      another SHR-Db group with placebo by gavage on a daily basis for 6 weeks.
      Myocardial structures were analyzed through light microscopy and stereology. In
      SHR-Db, the BP and the myocardium were significantly altered by oil
      supplementation. The BP, the interstitial fibrosis and cardiomyocyte size showed
      a significant decrease in treated SHR-Db than in SHR or untreated SHR-Db. The
      myocardial microvasculature and number of cardiomyocytes were higher in all
      treated groups, especially in fish oil group. Long-term edible oil
      supplementation showed beneficial effects decreasing BP levels and offsetting
      adverse myocardial remodeling in diabetic SHR.

PMID- 16303620
TI  - Regulation of the sphingolipid signaling pathways in the growing and hypoxic rat
      heart.
AB  - Sphingolipids (SLs) have a biomodulatory role in physiological as well as
      pathological cardiovascular conditions. This study aims to assess the variation
      of SL mediators and metabolizing enzymes in the growing and hypoxic rat heart.
      Sprague-Dawley rats were placed in a hypoxic environment at birth. Control
      animals remained in room air. In control animals, activities of acidic
      sphingomyelinase (A-SMase), sphingomyelin synthase (SMS), glucosylceramide
      synthase (GCS), and ceramidase decreased with age in both ventricles whereas
      activity of neutral-sphingomyelinase (N-SMase) increased with age. Hypoxic RV
      mass was 171 and 229% that of controls, at 4 and 8 weeks, respectively. This was
      accompanied by an increase in RV myocardial ceramide synthesis, consumption and
      breakdown, with a net effect of suppression of ceramide accumulation and increase
      in diacylglycerol (DAG) concentration. In addition, significant increase in
      activities of: A-SMase by 26 and 29%, SMS by 108 and 40%, and ceramidase by 66
      and 35%, in the hypoxic RV rats as compared to controls, was noted at 4 and 8
      weeks of age, respectively. Sphingolipids and their regulating enzymes appear to
      play a role in adaptive responses to chronic hypoxia in the neonatal rat heart.

PMID- 16303621
TI  - In vivo progestin treatments inhibit nitric oxide and endothelin-1-induced bovine
      endometrial prostaglandin (PG) E (PGE) secretion in vitro.
AB  - Synchronization of estrus with progestins in cows has been reported to inhibit
      nitric oxide (NO) and endothelin-1 (ET-1)-stimulated bovine luteal PGE secretion
      without affecting prostaglandin F2alpha (PGF2alpha) secretion in vitro [Weems YS,
      Randel RD, Tatman S, Lewis A, Neuendorff DA, Weems CW. Does estrous
      synchronization affect corpus luteum (CL) function? Prostaglandins Other Lipid
      Mediat 2004;74:45-59]. Two experiments were conducted to determine the effects of
      NO donors, endothelin-1 (ET-1), and NO synthase (NOS) inhibitors on bovine
      caruncular endometrial secretion of PGE and PGF2alpha in vitro. In Experiment 1,
      estrus was synchronized in Brahman cows with Synchromate-B ear implants, which
      contained the synthetic progestin norgestamet. Days 14-15 caruncular endometrial
      slices were weighed, diced, and incubated in vitro with treatments. Treatments
      (100 ng/ml) were: Vehicle (control), l-NAME (NOS inhibitor), l-NMMA (NOS
      inhibitor), DETA (control), DETA-NONOate (NO donor), sodium nitroprusside (NO
      donor), or ET-1. In Experiment 2, estrus was synchronized in Brahman cows with
      either Lutalyse (PGF2alpha) or a controlled intravaginal drug releasing device
      (CIDR-containing progesterone) or estrus was not synchronized. Days 14-15
      caruncular endometrial slices were weighed, diced, and incubated in vitro with
      treatments. Treatments (100 ng/ml) were: vehicle, l-NAME, l-NMMA, DETA, DETA
      NONOate, sodium nitroprusside, SNAP (NO donor) or ET-1. Tissues were incubated in
      M-199 for 1h without treatments and with treatments for 4 and 8h in both
      experiments. Media were analyzed for concentrations of PGE and PGF2alpha by
      radioimmunoassay (RIA). Hormone data in Experiments 1 and 2 were analyzed by 2x7
      and 3x2x8 factorial design for ANOVA, respectively. Concentrations of PGE and
      PGF2alpha in media increased (P< or =0.05) from 4 to 8 h regardless of treatment
      group in Experiment 1, but did not differ (P> or =0.05) among treatments. In
      Experiment 2, concentrations of PGE and PGF2alpha increased (P< or =0.05) with
      time in all treatment groups of all three synchronization regimens. DETA-NONOate,
      SNAP, and sodium nitroprusside (NO donors) and ET-1 increased caruncular
      endometrial (P< or =0.05) secretion of PGE2 in unsynchronized and Lutalyse
      synchronized cows, but not when estrus was synchronized with a CIDR (P> or
      =0.05). No treatment increased (P> or =0.05) PGF2alpha in any synchronization
      regimen. It is concluded that norgestamet in Synchromate-B ear implants or
      progesterone in a CIDR alters NO or ET-1-induced secretion of PGE by bovine
      caruncular endometrium and could interfere with implantation by altering the
      PGE:PGF2alpha ratio resulting in increased embryonic losses during early
      pregnancy.

PMID- 16303622
TI  - Regulation of prostaglandin synthesis by interleukin-1alpha in bovine endometrium
      during the estrous cycle.
AB  - Interleukin (IL)-1 has been suggested to participate in regulation of many
      reproductive functions. To investigate the possible role of IL-1alpha as a local
      regulator in bovine endometrium, we determined the effects of IL-1alpha on
      prostaglandin (PG) E2 and PGF(2alpha) output by the bovine endometrium at
      different stages of the estrous cycle. The expressions of IL-1alpha and IL-1
      receptor type 1 (IL-1RT1) mRNA in bovine endometrium were also studied. Bovine
      uteri were classified into six stages (estrus: day 0; early luteal: days 2-3;
      developing luteal: days 5-6; mid luteal: days 8-12; late luteal: days 15-17; and
      follicular: days 19-21). After 1h of pre-incubation, endometrial tissues (20
      30mg) were exposed to 0 or 10ng/ml IL-1alpha for 4h. IL-1alpha significantly
      stimulated PGE2 output throughout the luteal stages, with the highest response
      during the mid luteal stage, while it did not stimulate PGE2 output during the
      estrus and the follicular stage. On the other hand, IL-1alpha significantly
      enhanced PGF(2alpha) output throughout the estrous cycle except in the
      endometrium from the mid luteal stage, with the highest response at the
      follicular stage (P<0.001). The treatment of endometrial tissue with IL-1alpha
      resulted in an increase of the PGE2:PGF(2alpha) ratio at the mid luteal stage,
      and in a decrease during the late luteal and follicular stages of the estrous
      cycle. A semiquantitative reverse transcription-polymerase chain reaction
      revealed that IL-1alpha and IL-1RT1 mRNA are expressed in the endometrium
      throughout the estrous cycle. IL-1alpha mRNA expression was greater in the early
      luteal stage than in the estrus, late luteal, and follicular stages (P<0.05). IL
      1RT1 mRNA was greater in the late luteal stage than in the other stages (P<0.05).
      The overall results suggest that IL-1alpha is produced in bovine endometrium
      throughout the estrous cycle, and plays some roles not only in maintenance of CL,
      but also in luteolysis by regulating the local PGE2:PGF(2alpha) ratio in bovine
      endometrium during the estrous cycle.

PMID- 16303623
TI  - Urinary leukotriene E4 excretion is increased in type 1 diabetic patients: a
      quantification by liquid chromatography-tandem mass spectrometry.
AB  - OBJECTIVE: Diabetes mellitus is associated with inflammatory state and increased
      cardiovascular mortality. Leukotrienes are arachidonic acid metabolites derived
      from the 5-lipoxygenase pathway that possess vasoactive, chemotactic and
      proinflammatory properties. The aim of this study was to evaluate (1) the urinary
      excretion of leukotriene E4 (LTE4) in type 1 diabetic subjects and healthy
      volunteers and (2) the influence of glycemic control attested by HbA(1C) on LTE4
      excretion. METHODS AND RESULTS: Urinary excretion of LTE(4), measured by liquid
      chromatography-tandem mass spectrometry, was significantly (P=0.033) increased in
      diabetic patients (median [10th-90th percentiles]: 42.1 pg/mg creatinine [16.7
      71.4], n=34), compared to healthy subjects (25.5 pg/mg creatinine [13.9-54.1],
      n=28). Subgroup analysis indicated a trend towards increased LTE4 excretion in
      patients with poor glycemic control [(HbA(1C)> or =9% or plasma glucose >18
      mmol/L): 43.3 pg/mg creatinine [21.6-70.5], n=14], whereas no difference was
      observed between patients with good metabolic control [(HbA(1C)< or =7.5%): 36.4
      pg/mg creatinine [15.8-83.4], n=20] and healthy subjects. CONCLUSIONS: This study
      suggested that increased LTE4 excretion in type 1 diabetic state might reflect
      systemic activation of the 5-lipoxygenase pathway. It could be a determinant of
      underlying inflammatory state and vascular disease.

PMID- 16303624
TI  - Vibrational studies on the selective solvation of Na+ and ClO3- ions in
      dimethylformamide-formamide mixture.
AB  - Raman and infrared spectra of sodium chlorate in binary mixture of N,N
      dimethylformamide (DMF) and formamide (FA) were obtained. The addition of FA to
      the NaClO3-DMF system allow us to observe a new band at 1709 cm-1. This has been
      possible since the large dissociation of Na+ and ClO3- ions produced by the
      addition of FA helps to observe the coordination effect of DMF on the Na+ ions,
      in full agreement with the Gutmann donor number of this later. Quantitative
      measurements performed in the CO stretching region in the binary mixture give a
      solvation number value for the sodium cation equal at 3 in full agreement with
      others authors. In the NH stretching region of FA, the arising of the 3580 cm-1
      band is assigned to FA-ClO3- interactions via hydrogen bonding. In addition, our
      results show that the solvation number of the sodium cation remain constant in
      all concentration range studied. Such fact suggests that mixture of solvents with
      considerable differences in the donor-acceptor characters can be used to prepare
      electrolyte solutions where the ion pairs formation seems uncertain.

PMID- 16303625
TI  - EPR and optical investigations of manganese ions in alkali lead tetraborate
      glasses.
AB  - Electron paramagnetic resonance (EPR) and optical absorption spectra of Mn2+ ions
      in different alkali lead tetraborate glasses 90R2B4O7+9.25PbO+0.75MnSO4 (R=Li, Na
      and K) and 90Li2B4O7+(10-x)PbO+xMnSO4 (x=0.1, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5 and
      2 mol%) have been studied. The EPR spectrum of all the glass samples exhibit
      three resonance signals at g=2.0, 3.3 and 4.3. The resonance signal at g=2.0 is
      attributed to the Mn2+ ions in an environment close to an octahedral symmetry.
      The resonance signals at g=3.3 and 4.3 have been attributed to the rhombic
      symmetry of the Mn2+ ions. The effect of temperature (123-433 K) and the
      composition dependence of EPR signals have been studied for Mn2+ ions in lithium
      lead tetraborate glasses. It is interesting to observe that the variation of
      paramagnetic susceptibility (chi) with temperature obeys Curie-Weiss law. From
      the slope of 1/chi versus T graph, the Curie constant (C) has been evaluated. The
      zero-field splitting (zfs) parameter D has been calculated for different alkali
      lead tetraborate glasses from the intensities of the allowed hyperfine lines. The
      optical absorption spectrum exhibits three bands. An intense and broad band at
      lower energy side has been assigned to the spin-allowed (5Eg-->5T2g) transition
      of Mn3+ ions in an octahedral symmetry. The intense and sharp band and a broad
      band at higher energy side have been assigned to charge transfer bands. A red
      shift is observed with increase of alkali ion size. The optical band gap energy
      (Eopt) decreases, whereas the Urbach energies (DeltaE) increases with increase of
      Mn content. The theoretical values of optical basicity (Lambdath) of the glasses
      have also been evaluated.

PMID- 16303626
TI  - Structural and vibrational investigation of para-nitraminopyridine N-oxide. A
      combined experimental and theoretical studies.
AB  - The X-ray and vibrational spectroscopic analysis of para-nitraminopyridine N
      oxide are reported. The crystals of investigated compound belong to P2(1) of the
      monoclinic system, Z=4, a=3.735 A, b=11.767 A, c=14.679 A and beta=93.27 degrees
      . Room temperature powder infrared and Raman spectra of the title compound and
      its deuterated analogue were measured. The molecular structure of p
      nitraminopyridine N-oxide has been calculated with the aid of density functional
      (B3LYP) method with the extended 6-311++G(d,p) basis set. The calculated
      geometrical parameters of investigated molecule in gas phase were compared with
      experimental X-ray data. The harmonic frequencies, potential energy distribution
      (PED) and IR intensities of p-nitroaminopyridine N-oxide and its deuterated
      analogue were calculated with B3LYP method. The assignment of the experimental
      spectra has been made on the basis of the calculated PED. The time depend Hartree
      Fock (TDHF) method was used for calculations of hyperpolarizability beta
      coefficient.

PMID- 16303627
TI  - Raman spectrum, conformational stability, barriers to internal rotations and DFT
      calculations of 1,1,1-trifluoro-propane-2-thione with double-internal-symmetric
      rotor.
AB  - The Raman spectrum (3500-100 cm-1) of 1,1,1-trifluoro-propane-2-thione (TFPT),
      CF3C(S)CH3 of the solid phase has been recorded. The internal rotation of CH3
      and/or CF3 moieties around CC bonds in TFPT allow five hypothetical conformers
      (Cs and C1 point groups). Aided by quantum chemical (QC) calculations, the Cc
      conformer is the only stable form (CF3 and CH3 groups are eclipsing the CS bond)
      which contains a planar FCC(S)CH backbone and possess intramolecular hydrogen
      sulfur interactions. However, other conformations (with the orientation of sulfur
      atom being trans to either hydrogen or fluorine atom) are either transition
      states or not fully converged geometry with "gauche" orientation. Moreover, the
      calculation were carried out at the level of Becke three Lee-Yan-Parr (B3LYP)
      parameters up to 6-311++G(d,p) basis sets. The torsional barriers are adequately
      described by a three-fold potential, V3 which have been determined utilizing the
      optimized structural parameters from the B3LYP/6-31G(d) basis set along with
      potential surface scan. Barriers of 1.28 kcal/mol (448 cm-1) and 1.94 kcal/mol
      (678 cm-1) were calculated for CH3 and CF3 symmetric rotors, respectively.
      Complete vibrational assignments have been reported for the stable Cc isomer
      which is supported by normal coordinate analysis and potential energy
      distributions (PEDs) for all fundamentals. Moreover, equilibrium geometries,
      vibrational frequencies are compared to the corresponding experimental values of
      acetone, 1,1,1-trifluoroacetone (TFA), hexafluoroacetone (HFA) and other
      molecules having the CF3 moiety whenever appropriate.

PMID- 16303628
TI  - Vibrational and thermal studies of the complexes (NH4)[VO(O2)2(phen)].2H2O and
      (NH4)[V(O2)3(phen)].2H2O.
AB  - The infrared spectra of the oxodiperoxo and triperoxo complexes,
      (NH4)[VO(O2)2(phen)].2H2O and (NH4)[V(O2)3(phen)].2H2O have been recorded and the
      observed bands are assigned on the basis of Cs symmetry. Thermogravimetric (TG)
      and differential thermal analysis (DTA) measurements on these two complexes were
      also carried out. A detailed mechanism for the mode of thermal decomposition of
      the two complexes has been given and supported by infrared spectral measurements
      on the thermal decomposition products. The data obtained agree quite well with
      the expected structure and indicate that the final thermal decomposition product
      of these two complexes is V2O5.

PMID- 16303629
TI  - Spectral and theoretical studies of N-p-(ethylbenzene)thiobenzohydroxamic acid
      metal chelates.
AB  - The preparation of N-p-(ethylbenzene)thiobenzohydroxamic acid chelates with
      several metal ions and their spectral properties are described in this paper.
      This is followed by a theoretical study of metal complexes of some thiohydroxamic
      acids, as well as the prepared chelates. The electronic properties of the metal
      complexes are discussed. The experimental and theoretical electronic spectra are
      also compared. A possible reason for the smaller pKa values of thiohydroxamic
      acid complexes than those of the corresponding hydroxamic acids is given.

PMID- 16303630
TI  - Distinction between some saccharides in scattered optical sum frequency intensity
      images.
AB  - Using an optical sum frequency (SF) microscope with visible and infrared light
      pulses for excitation, we have attempted to distinguish among four saccharide
      species. The saccharides we studied were d-glucose, amylopectin, beta
      cyclodextrin, and amylose. The wavelength of the infrared light was resonant to
      CH vibration. Amylose showed very weak sum frequency scattering for CH vibration
      among the four saccharides. As for the other three saccharides, we found a big
      difference in the sum frequency spectra of their CH stretching vibration near
      2900 cm-1, when the incident visible and infrared light pulses were p- and s
      polarized, respectively. Based on these facts, we have demonstrated a distinction
      between these three saccharides in the scattered SF intensity images.

PMID- 16303631
TI  - Density functional theory studies on the Raman and IR spectra of meso
      tetraphenylporphyrin diacid.
AB  - The vibrational spectra of meso-tetraphenylporphyrin diacid (H4TPP2+) have been
      studied with the density functional theory. Raman and IR spectra of H4TPP2+ and
      its N-deuterated analogue (D4TPP2+) are measured and compared with the
      computational results. Complete assignments of observed IR and Raman bands were
      proposed on the bases of calculation results. The DFT calculations reproduce 140
      observed fundamentals with the RMS 8.6 cm-1. The computational as well as the
      experimental results reveal that the saddle-distortion of porphyrin macrocycle
      for the diacid leads to a significant effect on its vibrational spectra.
      Especially, several out-of-plane skeletal modes, which were either unobserved or
      very weak in the Raman spectra of CuTPP and H2TPP, are activated in the Raman
      spectra of the diacids. In addition, enhancement for the Raman bands of phenyl CC
      stretching modes were observed and attributed to the conjugation effect of pi
      systems of the phenyl and the porphyrinato macrocycles.

PMID- 16303632
TI  - Synthesis and fluorescence properties of rare earth (Eu3+ and Gd3+) complexes
      with alpha-naphthylacetic acid and 1,10-phenanthroline.
AB  - Rare earth binary complex Eu(NNA)3 (NNA, alpha-naphthylacetic acid), ternary
      complex Eu(NNA)3.phen (phen, 1,10-phenanthroline) and a series of dinuclear
      complexes with different mole ratios of Eu3+ to Gd3+ were synthesized. Many
      advanced approaches, such as element analysis, FTIR spectra, TG and DTA analysis,
      were used to determine the composition and structure of binary and ternary
      complex. Moreover, their fluorescence properties were studied by fluorescent
      spectra and lifetimes. The fluorescence spectra and decay curves of dinuclear
      complexes indicated that the fluorescence emission intensity was enhanced and the
      fluorescence lifetime was prolonged by Gd3+. The dinuclear complexes show the
      best properties when the mole ratio of Eu3+ to Gd3+ is 6:4. A new parameter Y,
      which was used to evaluate the effect of Gd3+, was introduced. In addition, the
      relationship of Y value and mole fraction of Gd3+ was analyzed by mathematical
      software. The results showed that Y value decreased by single exponential mode
      when the content of Gd3+ decreased.

PMID- 16303633
TI  - NIR spectroscopy of jarosites.
AB  - Near-infrared (NIR) spectroscopy has been used to analyse a suite of synthesised
      jarosites of formula Mn(Fe3+)6(SO4)4(OH)12 where M is K, Na, Ag, Pb, NH4+ and
      H3O+. Whilst the spectra of the jarosites show a common pattern, differences in
      the spectra are observed which enable the minerals to be distinguished. The NIR
      bands in the 6300-7000 cm-1 region are attributed to the first fundamental
      overtone of the infrared and Raman hydroxyl stretching vibrations. The NIR
      spectrum of the ammonium-jarosite shows additional bands at 6460 and 6143 cm-1,
      attributed to the first fundamental overtones of NH stretching vibrations. A set
      of bands are observed in the 4700-5500 cm-1 region which are assigned to
      combination bands of the hydroxyl stretching and deformation vibrations. The
      ammonium-jarosite shows additional bands at 4730 and 4621 cm-1, attributed to the
      combination of NH stretching and bending vibrations. NIR spectroscopy has the
      ability to distinguish between the jarosite minerals even when the formula of the
      minerals is closely related. The NIR spectroscopic technique has great potential
      as a mineral exploratory tool on planets and in particular Mars.

PMID- 16303634
TI  - The investigation of a series of n-hydroxybenzoic acids (n=p, m, o) on a new
      surface enhanced Raman scattering active substrate.
AB  - Ag nanoparticles, organized on indium tin oxide (ITO) surface, can act as a new
      surface enhanced Raman scattering (SERS) active substrate as well as a dry
      electrode. Compared with the traditional SERS-active substrate, its notable
      advantage is that the microcosmic changes of the film can be reflected by the
      SERS spectrum during the investigation of the film's electrical and other
      macroscopic characteristics. To illuminate the above-mentioned property of this
      new substrate, a series of n-hydroxybenzoic acids (n-HBA; n=p, m and o) was
      tested as probe molecules by SERS technique. These SERS spectra indicate that the
      significant changes of frequencies as well as intensities, respectively, arise
      from the changes of the adsorption behavior along with the proportional variation
      of molecules and silver nanoparticles. Excellent SERS signals prove that the
      silver nanoparticles-coated ITO is a highly SERS-active substrate and can
      efficiently reflect the microcosmic property of the film, which suggest it has
      promising potential of being a new technique for further application in the field
      of thin-film research.

PMID- 16303635
TI  - Anti-proteinuric effect of an N-type calcium channel blocker, cilnidipine.
AB  - The objective of the present study was to determine anti-proteinuric effect of an
      N-type calcium channel blocker-cilnidipine. Subjects were 43 essential or renal
      hypertensive subjects who had been taking calcium channel blockers other than
      cilnidipine for at least 6 months. All patients had proteinuria greater than 0.2
      g/day in spite of fair blood pressure control (<150/90 mmHg). Calcium channel
      blockers in 25 patients (62+/-3 years) were switched to cilnidipine (cilnidipine
      group), whereas other 18 patients (58+/-3 years) continued to take originally
      prescribed calcium channel blockers (control group). The 24-hr urine collections
      were done at baseline and after 6 months of the follow-up period. Baseline
      characteristics including age, blood pressure levels, body mass index and
      creatinine clearance were similar between cilnidipine and control groups. Urinary
      protein excretion also was comparable between cilnidipine (0.61+/-0.10 g/day) and
      control (0.86+/-0.17 g/day) groups. Urinary protein significantly decreased after
      6 months in cilnidipine group (- 0.21+/- 0.11 g/day, - 36%, p< 0.01), whereas it
      did not change in control group (+ 0.01+/- 0.15 g/day, 0.4%, ns). There were no
      significant changes in blood pressure, serum creatinine, creatinine clearance,
      estimated protein intake, and urinary salt excretion during the follow-up period
      in either group. The reduction of urinary protein by cilnidipine was evident in
      essential hypertensives (- 54+/-9%, n=18, p<0.01) but not in renal hypertensives
      (+10+/-35%, n=7, ns). Results suggest that cilnidipine has an anti-proteinuric
      effect especially in patients with essential hypertension.

PMID- 16303636
TI  - Gonadectomy and androgen replacement alter cardiac performance in conscious adult
      male rats.
AB  - Gender disparities in cardiac function have been described. Yet the extent to
      which gender related differences in cardiac performance are due to the presence
      of sex-specific biological factors are unclear. We used a longitudinal study
      aimed at examining whether castration and androgen replacement affects cardiac
      performance in conscious adult male rats. Adult male rats were implanted with
      Piezoelectric transit-time gauges and radio telemetry devices to measure regional
      myocardial segment length and hemodynamic variables before and after castration
      and after androgen replacement. Androgen withdrawal accelerated average heart
      rates by 7% (p=0.010). Heart rate was lowered to intact values when androgens
      were restored to normal physiological levels (p=0.004). Mean arterial pressure
      was not affected by androgen deprivation and androgen replacement. However,
      androgen withdrawal produced a 40% decrease in the velocity of circumferential
      shortening and a 46% reduction in the rate of myocardial relaxation. Androgen
      supplementation completely restored contractile function. These results provide
      the first evidence that androgen withdrawal and androgen replacement produces
      dramatic alterations on cardiac performance in conscious animals and demonstrates
      the significance of androgens as a cardio-regulatory hormone in males. Sex
      steroids are likely contributors to gender-related differences in cardiac
      function.

PMID- 16303637
TI  - A rat model of preeclampsia.
AB  - Preeclampsia/eclampsia is a disorder of human pregnancy that continues to exact
      significant maternal morbidity and mortality and fetal wastage. Therapy of these
      disorders has not changed in over 50 years and there are no proven preventive
      measures. We describe a model of the development of a syndrome in the pregnant
      rat that resembles preeclampsia, which results from the imposition of excessive
      volume expansion early in gestation. We administered desoxycorticosterone acetate
      (DOCA) to pregnant animals whose drinking water had been replaced with saline. We
      compared the results obtained in these animals with those resulting from the
      study of control, virgin animals, virgin animals receiving DOCA and saline, and
      normal pregnant (NP) animals. The virgin animals given DOCA and saline did not
      become hypertensive. The experimental paradigm in the DOCA plus saline pregnant
      (PDS) animals provides many of the phenotypic characteristics of the human
      disorder including the development of hypertension, proteinuria, and intrauterine
      growth restriction. In addition, the mean blood nitrite/nitrate concentration was
      reduced in the PDS rats compared with their NP counterparts. We propose that this
      model may prove to be useful in the study of the human condition.

PMID- 16303638
TI  - Central actions of agmatine in conscious spontaneously hypertensive rats.
AB  - Agmatine (decarboxylated arginine) is an endogenous ligand at alpha-2 adrenergic
      and imidazoline nonadrenergic receptors. In conscious spontaneously hypertensive
      rats (SHRs), we have studied its central effects on cardiovascular function and
      its interaction with the second generation centrally acting antihypertensive
      agent, rilmenidine, and the reference imidazoline, clonidine, which are mixed
      alpha-2 adrenoceptor/imidazoline receptor agonists. Agmatine, when administered
      in low doses (30-100 microg/kg) into the fourth ventricle had no effect on blood
      pressure and caused an increase in heart rate. A higher dose of 1,000 microg/kg
      produced an adverse reaction in conscious SHRs and a marked and long-lasting
      increase in blood pressure. The effects of fourth ventricular rilmenidine (300
      microg/kg) and clonidine (10 microg/kg) were equihypotensive and equibradycardic.
      The antihypertensive and bradycardic effects of rilmenidine were not reversed by
      cumulative intracisternal doses (30-100-300 microg/kg) of agmatine. The
      bradycardia obtained 20 min after intracisternal administration of clonidine in
      the fourth ventricle was reversed by 30 microg/kg agmatine. Only the highest dose
      of agmatine (1,000 microg/kg) did reverse the antihypertensive effects of
      rilmenidine and clonidine. Agmatine neither did mimic nor block the
      antihypertensive response to rilmenidine and clonidine at well-tolerated doses.
      Yet agmatine produced a small tachycardia at relatively low doses and was able to
      reverse the bradycardia induced by clonidine. Therefore, its affinity for alpha-2
      adrenoceptors in vitro might partially explain its cardiovascular effects in
      vivo.

PMID- 16303639
TI  - Soluble CD40 ligand levels in patients with hypertension.
AB  - CD40 ligand interaction with its receptor (CD40) not only mediates lymphocyte
      communication, but also associates with chronic inflammation and
      atherothrombosis. High soluble CD40L (sCD40L) levels were reported in
      dyslipidemia, diabetes mellitus, and coronary disease. So far, there are no data
      about sCD40L levels in hypertension. We investigated sCD40L and high sensitive C
      reactive protein (hsCRP) levels in 30 nonobese young hypertensive men and 30
      matched controls. sCD40L and hsCRP levels were not different, and there were no
      correlations between blood pressure and sCD40L or hsCRP levels. These results
      might indicate lack of any inflammatory state in new onset hypertension.

PMID- 16303641
TI  - 16th International Symposium on ALS/MND, Dublin, Republic of Ireland, 8-10
      December 2005. Abstracts.

PMID- 16303640
TI  - Valsartan abolishes most of the memory-improving effects of
      intracerebroventricular angiotensin II in rats.
AB  - This study explores behavioral effects of angiotensin II (Ang II) and a potent
      AT(1) receptor inhibitor valsartan ((S)-N-valeryl-N-{[2'-(1H-tetrazol-5
      yl)biphenyl-4-yl]-methyl}-valine). Male Wistar rats (160-180 g) were administered
      valsartan (10 mg/kg) orally followed, 2 hr later, by Ang II (1 nmol) given
      intracerebroventricularly (i.c.v., right lateral ventricle). Then 15 min later
      rats underwent behavioral testing: acquisition of conditioned avoidance responses
      (CARs), recall of a passive avoidance behavior, open field, elevated "plus" maze,
      and "chimney" test. Object recognition was tested 60 min after the i.c.v.
      injections. In addition, effect of valsartan on Ang II stimulated drinking of
      water was tested. We found that valsartan did not modify the Ang II facilitation
      of CARs acquisition but abolished the Ang II improvement of memory retrieval and
      consolidation. The lack of effect of our treatments on the rats' motor activity
      in the open field makes unspecific contribution of the drug-induced performance
      changes to the cognitive tests improbable. The anxiogenic action of Ang II,
      decreased by valsartan, makes an unspecific influence of anxiety possible. The
      prevention of Ang II increase of drinking by orally given valsartan confirmed
      effective blockade of the brain AT(1) receptors by the drug. IN CONCLUSION:
      valsartan appears to affect cognitive effects of i.c.v. Ang II in rats in a
      similar way to losartan; anxiolytic activity of valsartan appears to be slightly
      weaker than that of losartan.

PMID- 16303670
TI  - Vestibular malformation in mice lacking Na-K-2Cl cotransporter 1 and expression
      of Na-K-2Cl cotransporter 1 in human vestibular end organs.
AB  - CONCLUSION: The Na-K-2Cl cotransporter-1 (NKCCl) may be essential for the
      maintenance and functioning of the vestibular morphology in mice and it is
      strongly expressed in human vestibular end organs. OBJECTIVE: NKCCl is a member
      of the cation-coupled chloride transporter which participates in salt transport
      and cell volume regulation in diverse tissues. NKCCl-deficient mice exhibit
      deafness, and show structural alterations in the cochlea. In addition to hearing
      loss, NKCCl-deficient mice show a shaker-waltzer behavior, which suggests a
      vestibular system defect. In this study we investigated the morphology of the
      vestibular system of NKCCl-deficient mice and also evaluated whether NKCCl mRNA
      and its protein are expressed in human vestibular end organs. MATERIAL AND
      METHODS: NKCCl-deficient and wild-type mice aged 4-5 weeks were sacrificed. Their
      heads were cut in the midsagittal plane, fixed and decalcified. For light
      microscopy, 5-microm sections were cut and stained with hematoxylin-eosin. Human
      vestibular end organs were harvested during acoustic tumor surgery via a
      translabyrinthine approach. Some of these end organs were used for total mRNA
      extraction and the remainder for immunostaining. Reverse transcriptase polymerase
      chain reaction and immunostaining were performed for NKCCl. RESULTS: The scala
      media of the cochleae of the NKCCl-deficient mice had collapsed but the bony
      labyrinth appeared unaffected. However, the semicircular canals (SCCs) were much
      smaller than those in the wild-type mice. Furthermore, the SCCs were completely
      missing in some NKCCl-deficient mice. NKCCl mRNA was expressed in both the human
      macula and crista ampullaris, and its protein was expressed mainly in the
      transitional and dark cell areas of the human crista ampullaris.

PMID- 16303671
TI  - Immunocytochemical and stereological study of glucocorticoid receptors in rat
      medial vestibular nucleus neurons and the effects of unilateral vestibular
      deafferentation.
AB  - CONCLUSION: The results of this study suggest that neither the number of medial
      vestibular nucleus (MVN) neurons expressing cytosolic glucocorticoid receptors
      nor blood corticosterone levels change significantly during the development of
      vestibular compensation. OBJECTIVE: Vestibular compensation is a process of
      partial behavioral recovery that occurs following damage to the vestibular
      labyrinth. It has been suggested that this compensation process might be
      dependent on the release of glucocorticoids such as corticosterone at the time of
      unilateral vestibular deafferentation (UVD) and that changes in glucocorticoid
      receptors in the MVN might contribute to the initiation of the compensation
      process. MATERIAL AND METHODS: We compared the number of MVN neurons expressing
      cytosolic glucocorticoid receptors in rats at 10 h and 2 weeks following UVD, and
      in sham and anesthetic control animals; we also measured blood corticosterone
      levels. RESULTS: Using immunocytochemistry and stereology, we found that the
      majority of MVN neurons expressed glucocorticoid receptors, but there were no
      significant differences in the number of glucocorticoid receptor-expressing
      neurons in the ipsilateral or contralateral MVNs at 10 h or 2 weeks post-UVD;
      furthermore, corticosterone levels did not vary significantly between the UVD and
      control groups.

PMID- 16303672
TI  - Prediction of vestibulo-autonomic symptoms during the caloric test: evaluation of
      autonomic activity by spectral analysis of the electrocardiographic R-R interval.
AB  - CONCLUSION: If the high-frequency (HF) component of the R-R interval spectrum of
      the electrocardiogram (ECG) increases after the first stimulation during a
      bithermal caloric test, subsequent repeated stimulations may be likely to induce
      autonomic symptoms such as nausea. OBJECTIVE: Nausea often occurs as a vestibulo
      autonomic symptom during the caloric test. However, there have been only a few
      clinical studies of autonomic activity during this test. To determine whether
      certain factors can predict the development of nausea, we performed an autonomic
      function test by means of R-R interval spectral analysis of the ECG during
      caloric testing. MATERIAL AND METHODS: The study subjects were 53 healthy
      volunteers aged 22-39 years (41 males, 12 females; mean age 25.3 years) and a 35
      year-old male patient with a labyrinthine defect. The caloric test was performed
      in 43 subjects using an air caloric apparatus with bithermal stimulation of
      alternate ears. After each stimulation, the subjects were asked about autonomic
      symptoms. Serial ECG records were obtained and R-R interval spectral analysis was
      performed. RESULTS: Severe nausea was observed in 12 subjects (28%). In the group
      with severe nausea, the HF component of the R-R interval spectrum increased after
      the first caloric stimulation when autonomic symptoms had not yet become marked.

PMID- 16303673
TI  - Speech perception in elderly patients following cochlear implantation.
AB  - CONCLUSIONS: Elderly patients benefit from cochlear implantation in terms of
      speech perception and quality of life. Age alone should be no contraindication
      for implantation. OBJECTIVE: There have been concerns whether elderly patients
      may perform poorly after cochlear implantation due to degenerative processes in
      the central and peripheral auditory systems. The purpose of this study was to
      analyze the benefits of cochlear implantation in elderly patients in comparison
      to younger recipients. MATERIAL AND METHODS: We examined 26 postlingually
      deafened adults aged > 65 years who received a cochlear implant at our center
      regarding preoperative findings, comorbidities, postoperative complications and
      quality of life. Speech perception was assessed by means of multi- and
      monosyllabic word recognition and compared to the results obtained by younger
      patients. RESULTS: The surgical procedure was well tolerated by all patients
      without notable perioperative complications. In terms of speech perception, no
      significant differences between the elderly patients and younger recipients were
      noted. All patients found that cochlear implantation had a positive impact on
      their quality of life.

PMID- 16303674
TI  - Human leukocyte antigen-DQB1 and -DRB1 associations in patients with idiopathic
      sudden sensorineural hearing loss from a defined population of Northwest Spain.
AB  - CONCLUSION: The results of this study support the assertion that Southern
      European individuals have a genetically mediated predisposition to develop
      idiopathic sudden sensorineural hearing loss (SNHL). OBJECTIVE: To assess the
      influence of human leukocyte antigen (HLA)-DQB1 and -DRB1 alleles on the
      susceptibility to and the severity of idiopathic sudden SNHL. MATERIAL AND
      METHODS: A prospective study of patients diagnosed with idiopathic sudden SNHL
      between October 2000 and September 2002 was conducted. Patients were included in
      the study if they were diagnosed with idiopathic sudden SNHL within 1 week after
      the onset of deafness symptoms and had been followed for at least 12 months. HLA
      DQB1 and -DRB1 typing was performed from DNA using molecular-based methods on
      patients and ethnically matched healthy controls. RESULTS: Thirty-three patients
      fulfilled the inclusion criteria. No significant differences in HLA-DQB1
      phenotype frequencies were found between patients and controls (n = 145).
      Carriage of HLA-DRB1*0403 was significantly increased in the whole group of
      patients compared with controls (OR = 11.97; 95% CI 1.99-91.60; p = 0.002;
      p(corr) = 0.04). In patients without auditory improvement the frequency of the
      HLA-DRB1*04 phenotype was significantly increased compared with healthy controls
      (OR = 6.57; 95% CI 1.62-26.70; p = 0.003; p(corr) = 0.04).

PMID- 16303675
TI  - Meniett therapy: rescue treatment in severe drug-resistant Meniere's disease?
AB  - CONCLUSION: Our data indicate that Meniett therapy is unlikely to be helpful in
      the long-term treatment of patients with severe, drug-resistant Meniere's disease
      (MD) in whom injection of intratympanic gentamicin (ITG) or another destructive
      procedure would otherwise be performed. OBJECTIVE: To investigate the value of
      Meniett therapy in patients with drug-resistant MD referred for injection of ITG.
      MATERIAL AND METHODS: Twelve patients referred for ITG treatment were followed
      during a 2-month period of Meniett therapy. Symptoms, functional level and
      hearing status were evaluated using a standardized staging system. Disease
      specific quality-of-life measures were obtained before and after Meniett therapy.
      At the end of the study period, patients were followed for a mean of 37 months,
      thus providing long-term outcome data. RESULTS: In two patients, Meniett
      treatment was interrupted after 1 month because of persistent severe vertigo. In
      the remaining 10 subjects, we found a significant decrease in the median number
      of vertigo spells from 10.0/month (25th-75th percentile 4.0-19.0) prior to
      treatment to 3.0/month (25th-75th percentile 1.5-4.5) after treatment (p = 0.02).
      There was, however, no improvement in hearing status, tinnitus, functional level
      or self-perceived dizziness handicap. Long-term (>1 year) follow-up data revealed
      that only 2 subjects preferred to continue Meniett therapy and that ablative
      surgery had to be performed in 6/12 study patients.

PMID- 16303676
TI  - Radical scavengers: a remedy for presbyacusis. A pilot study.
AB  - CONCLUSION: The results of this study suggest that treatment with radical
      scavengers has the potential to become an effective new therapy for presbyacusis.
      OBJECTIVE: To assess the efficacy of treatment with the radical scavengers
      rebamipide and vitamin C for presbyacusis. MATERIAL AND METHODS: Rebamipide (300
      mg/day) and vitamin C (600 mg/day) were taken orally for at least 8 weeks by 23
      patients with presbyacusis. RESULTS: Hearing levels after treatment were
      significantly improved at 125, 250, 500 and 8000 Hz but unchanged at 1000, 2000
      and 4000 Hz.

PMID- 16303677
TI  - Effect of hypo-, iso- and hypertonic saline irrigation on secretory mucins and
      morphology of cultured human nasal epithelial cells.
AB  - CONCLUSION: We speculate that isotonic saline is the most physiological
      irrigation solution in terms of mucus secretion and the cellular morphology of
      nasal epithelial cells. OBJECTIVE: To determine the most physiologic and
      effective saline concentration for nasal irrigation in terms of mucus secretion
      and cellular morphology by using normal human nasal epithelial cells treated with
      hypo-, iso- and hypertonic saline. MATERIAL AND METHODS: Fully differentiated
      passage-2 normal human nasal epithelial cells were treated with pure water and
      with 0.3% (hypotonic), 0.9% (isotonic) and 3% (hypertonic) saline solutions. mRNA
      expression levels of MUC5AC and MUC5B, which are known to be major airway mucins,
      were analyzed after 30 min using reverse transcriptase polymerase chain reaction.
      Total mucin and MUC5AC and MUC5B mucin secretions were analyzed using dot
      blotting. Cellular morphology was observed with light microscopy after
      hematoxylin-eosin staining and with scanning electron microscopy. RESULTS: MUC5AC
      and MUC5B mRNA levels did not change after treatment with pure water and various
      concentrations of saline. Total mucin and MUC5AC mucin secretions only increased
      following pure water treatment, while MUC5B mucin secretion increased with pure
      water, hypo- and hypertonic saline treatment. Morphologic analysis revealed that
      pure water severely damaged normal human nasal epithelial cells and that only
      isotonic saline did not affect their morphology.

PMID- 16303678
TI  - Suppression of inflammation by dexamethasone prolongs adenoviral vector-mediated
      transgene expression in murine nasal mucosa.
AB  - CONCLUSION: The results of this study demonstrate that suppression of
      inflammation by dexamethasone attenuates the host immune response against
      adenoviral-mediated gene transfection and thereby prolongs transgene expression
      in murine nasal mucosa. OBJECTIVES: Gene transfer using a recombinant adenovirus
      is a good tool for research and clinical applications, but the immune response to
      adenoviral vectors can induce inflammation and loss of transgene expression in
      transfected tissues. In this study we investigated the effects of dexamethasone
      induced immunosuppression on adenovirus gene transfer in the nasal mucosa of the
      mouse. MATERIAL AND METHODS: We administered the recombinant adenovirus
      Ax1CAlacZ, which encodes Escherichia coli beta-galactosidase (lacZ gene), to the
      nasal mucosa of mice treated with or without i.p. dexamethasone and evaluated the
      expression of the lacZ gene on Days 2, 4, 7, 14 and 28. The nasal mucosa was
      dissected out, and the mRNA level was measured using a LightCycler. The
      expression of the exogenous beta-galactosidase was detected by means of
      histochemistry. RESULTS: Dexamethasone treatment significantly increased the mRNA
      level compared with that in the controls at Days 4, 7 and 14. Histochemistry
      showed that the expression of beta-galactosidase protein persisted in the
      dexamethasone-treated mice at Days 7 and 14 but had diminished almost to nothing
      in the control group.

PMID- 16303679
TI  - Paradoxical sensation of nasal airflow in patients with common cold. Are we
      measuring the correct modality?
AB  - CONCLUSIONS: A paradoxical relationship between objective and subjective measures
      of nasal obstruction exists in participants not exposed to any treatment. The
      sensation of nasal obstruction may be due to the amalgamation of many different
      nasal sensations. Improved methods for measuring nasal sensations are required to
      further investigate the relationship between objective and subjective measures of
      nasal obstruction. OBJECTIVES: In a recent study it was shown that the subjective
      sensation of nasal patency increased as the nasal passages became objectively
      more obstructed in patients who received a placebo compared to those who received
      an oral decongestant. This paradoxical response may be explained as a placebo
      effect, i.e. patients who received a placebo may have expected to feel less
      obstructed. The aim of the present study was to investigate this interesting
      paradox by determining objective and subjective measures of nasal obstruction
      over time in participants not exposed to any treatment. MATERIAL AND METHODS: A
      total of 60 healthy participants with common cold were recruited. Objective and
      subjective measures of nasal obstruction were recorded at baseline and at 1 and 2
      h using posterior rhinomanometry and a visual analogue scale. RESULTS: Objective
      measures demonstrated an increase in nasal obstruction over time for both nasal
      passages considered together and for individual nasal passages. Subjective
      measures demonstrated a sensation of decreased nasal obstruction over time for
      both nasal passages considered together and for individual nasal passages.

PMID- 16303680
TI  - Post-tonsillectomy haemorrhage: a retrospective comparison of abscess- and
      elective tonsillectomy.
AB  - CONCLUSION: There is no increased risk of postoperative haemorrhage for abscess
      tonsillectomies in comparison to elective tonsillectomies. OBJECTIVE: There is
      still controversy as regards the optimal management of peritonsillar abscess.
      Opponents of tonsillectomy a chaud cite an increased postoperative bleeding risk.
      Most authors who compared the risks of postoperative haemorrhage after
      tonsillectomy a chaud and tonsillectomy a froid did not take into consideration
      criteria such as the age and gender of the patients or the experience of the
      surgeon. We aimed to eliminate this bias by performing a retrospective study in
      which a large series of abscess tonsillectomies were compared with an age- and
      gender-matched group of elective tonsillectomies. MATERIAL AND METHODS: All
      patients had been operated on at the Department of Otorhinolaryngology,
      University of Duisburg-Essen between March 1994 and August 2000. There were 350
      patients in the abscess tonsillectomy group (61% male, 39% female; mean age 31.8
      years; range 3-88 years) and 311 in the elective tonsillectomy comparison group
      (61% male, 39% female; mean age 30.0 years; range 2-83 years). RESULTS: In the
      abscess tonsillectomy group, 9 patients (2.6%; confidence level 1.1-4.8%) had
      postoperative haemorrhages which required treatment under general anaesthesia,
      compared to 17 (5.5%; confidence level 3.2-8.6%) in the age- and gender-matched
      group of "selected" elective tonsillectomies. The difference between these two
      rates was not significant (p = 0.056). The fairly high rate of haemorrhages in
      the elective tonsillectomy group was mainly due to the effect of the age-matching
      procedure, which excluded a considerable number of usually unproblematic
      tonsillectomies for tonsillar hyperplasia in young children. Moreover, our
      results show that there is a learning curve for surgeons performing
      tonsillectomies with regard to postoperative haemorrhages.

PMID- 16303681
TI  - Diagnosis of major salivary gland tuberculosis: experience of eight cases and
      review of the literature.
AB  - CONCLUSIONS: Tuberculosis of the salivary gland is mostly a medically curable
      disease entity but early diagnosis is very important to ensure complete
      remission. In cases with a high index of suspicion, reliable diagnostic methods
      such as polymerase chain reaction (PCR) should always be considered before
      surgical intervention to enable differential diagnosis of a salivary gland tumor.
      OBJECTIVES: To investigate the clinical characteristics of major salivary gland
      tuberculosis and to review the literature relating to its diagnosis. MATERIAL AND
      METHODS: Eight patients diagnosed as having major salivary gland tuberculosis
      between 1994 and 2004 were treated at one of three tertiary referral centers.
      Medical records, including imaging findings and the results of microbiological
      tests, Mycobacterium tuberculosis PCR and histopathology, were retrospectively
      retrieved and the literature was reviewed. RESULTS: The parotid and submandibular
      glands were involved in 5 (62.5%) and 3 cases (37.5%), respectively. Neck CT
      demonstrated typical findings of salivary gland tuberculosis in 3 patients
      (37.5%). Fine-needle aspiration cytology revealed chronic inflammation in 6/7
      patients (85.7%), 2 of whom (33.3%) showed caseous necrosis, strongly suggesting
      tuberculosis. Five of the 8 patients (62.5%) required resection of the affected
      gland and 3 (37.5%) received open biopsy. PCR was performed in half of the cases
      and was affirmative in every case. No significant differences were found between
      the surgically resected and non-resected groups in terms of treatment results or
      morbidity. All patients received anti-tuberculous chemotherapy for 8-12 months,
      with no disease recurrence.

PMID- 16303682
TI  - Therapeutic management of laryngeal cancer. Results of a study of 356 patients
      from the Cancer Registry of the Somme, France.
AB  - CONCLUSIONS: The global survival rate was low compared to those reported in the
      literature, in which the analyzed populations were selected according to the
      tumor stage or treatment. This study should be prolonged and should also involve
      other cancer registries in France in order to increase the number of patients and
      to analyze tumors of comparable stage and therapeutic management. OBJECTIVE: To
      analyze the survival rate of a non-selected laryngeal cancer population from the
      Cancer Registry of the Somme, a French region. MATERIAL AND METHODS: A total of
      356 patients were included in a retrospective study covering the period 1987
      1997. Survival and prognostic factors were analyzed. Statistical analysis was
      performed using the Kaplan-Meier method, the Cox model and the chi2 test.
      RESULTS: The 5-year global survival rate was 42% for males and 55% for females.
      Tumor localization, T, N and M stages and surgery were found to be significant
      prognostic factors. Sex and age were not statistically significant factors. For
      stage I tumors, surgery alone gave better results than radiotherapy alone in
      terms of global survival. No difference occurred in terms of local recurrence. A
      similar comparison was not possible for stage II-IV tumors owing to the small
      number of cases.

PMID- 16303683
TI  - Oral status, oral infections and some lifestyle factors as risk factors for oral
      and oropharyngeal squamous cell carcinoma. A population-based case-control study
      in southern Sweden.
AB  - CONCLUSION: Our results show that average and poor oral hygiene and inadequate
      dental status are independent risk factors for oral and oropharyngeal squamous
      cell carcinoma (OOSCC), irrespective of tobacco and alcohol consumption.
      OBJECTIVE: To evaluate a possible relationship between oral cancer, oral hygiene,
      dental status, oral mucosal lesions and some lifestyle factors in a population
      based case-control study. MATERIAL AND METHODS: Between September 2000 and
      January 2004, 132/165 (80%) of all incident cases of OOSCC and 320/396 (81%) of
      the intended eligible matched controls participated in the study. Cases and
      controls were subjected to an identical oral examination. A standardized protocol
      specially designed for the study was used. RESULTS: After adjusting for tobacco
      and alcohol consumption, average oral hygiene (OR 2.0; 95% CI 1.1-3.6) and poor
      oral hygiene (OR 5.3; 95% CI 2.5-11.3) emerged as significant risk factors for
      OOSCC. More than 20 lost teeth (OR 3.4; 95% CI 1.4-8.5), >5 defective teeth (OR
      3.1; 95% CI 1.2-8.2) and poorly fitting or defective complete dentures (OR 3.8;
      95% CI 1.3-11.4) were significant risk factors. Regular dental check-ups were
      associated with a decreased risk of OOSCC (OR 0.4; 95% CI 0.2-0.6).

PMID- 16303684
TI  - Strong association between infection with human papillomavirus and oral and
      oropharyngeal squamous cell carcinoma: a population-based case-control study in
      southern Sweden.
AB  - CONCLUSIONS: The results of this study demonstrate a strong association between
      infection with high-risk types of human papillomavirus (HPV) and oral and
      oropharyngeal squamous cell carcinoma (OOSCC), suggesting that high-risk HPV
      types play a key role in carcinogenesis. The estimated proportion of OOSCC cases
      attributable to HPV infection was 35%. OBJECTIVE: HPV appears to have an
      aetiological role in OOSCC, despite the fact that the reported prevalences of HPV
      in both OOSCC patients and healthy individuals have varied widely. We aimed to
      investigate the presence and spectrum of both high- and low-risk HPVs in all
      consecutive cases of OOSCC in a Swedish healthcare region over a 3-year period
      and in population-based, matched healthy controls. MATERIAL AND METHODS: A total
      of 131 patients with OOSCC were studied. Samples taken from the surface of the
      tumour and from the tonsillar fossa using cotton-tipped swabs were investigated,
      together with exfoliated cells collected using a mouthwash. Tonsillar fossa and
      mouthwash specimens were collected in the same way from 320 matched controls. All
      samples were tested for HPV DNA by nested polymerase chain reaction using the
      primer pairs MY09/MY11 and GP5 + /GP6+, and in positive cases the HPV type was
      determined by DNA sequencing. RESULTS: Infection with high-risk HPV was shown to
      be a strong risk factor for OOSCC (OR = 63; 95% CI 14-480). Forty-seven (36%) of
      the cancer patients had > or =1 specimen that was positive for a high-risk HPV
      type (81% of which were HPV 16), while only 3 (0.94%) of the controls were
      positive for a high-risk HPV type. Seven (5.3%) of the cancer patients and 13
      (4.1%) of the controls were positive for any of the mucosal, mucocutaneous or
      cutaneous low-risk HPV types.

PMID- 16303685
TI  - Survivin expression and its relationship with apoptosis and prognosis in nasal
      and paranasal sinus carcinomas.
AB  - CONCLUSIONS: The inverse correlation found in this study between survivin
      expression and the level of spontaneous apoptosis in nasal and paranasal sinus
      carcinoma (NPSC) suggests that survivin may play an important role in the
      tumorigenesis of NPSC. Survivin expression may provide a novel predictive
      indicator for disease-free survival after surgical resection and postoperative
      radiochemotherapy in NPSC. OBJECTIVES: NPSC is the third commonest neoplasm in
      otolaryngology. Little is known about the distribution of inhibitors of apoptosis
      in NPSC and how they correlate with the prognoses of patients. The objectives of
      this study were to assess the protein expression of a new inhibitor of apoptosis,
      survivin, and its correlation with spontaneous apoptosis, tumor
      clinicopathological parameters and prognosis in NPSC. MATERIAL AND METHODS: A
      total of 48 patients (23 females, 25 males; age range 20-71 years) with NPSC
      treated by means of radical operations between 1991 and 2000 were studied
      retrospectively. Spontaneous apoptotic cells were visualized by means of terminal
      deoxynucleotide transferase-mediated dUTP nick-end labeling in combination with
      hematoxylin-eosin and propidium iodide staining. Immunohistochemistry using the
      streptavidin-peroxidase method was used to assess the expression of survivin.
      RESULTS: Survivin expression was positive in 23/48 samples (47.92%) but no
      staining was present in normal tissues adjacent to the tumors. The expression of
      survivin correlated negatively with the apoptotic index (r = - 0.393; p = 0.006).
      Patients with positive expression of survivin had a lower apoptotic index than
      those with negative expression (p < 0.05). The expression of survivin in advanced
      stage tumors (T3 + T4) was higher than that in early ones (T1 + T2) (p < 0.05).
      Patients with negative expression of survivin had a much better prognosis than
      those with positive expression (p = 0.0346). Multivariate analyses revealed that
      expression of survivin and histological type were independent prognostic factors
      for overall survival.

PMID- 16303686
TI  - Magnetoencephalography and positron emission tomography studies of a patient with
      auditory agnosia caused by bilateral lesions confined to the auditory radiations.
AB  - The aim of this study was to investigate auditory cortex function in the context
      of auditory stimuli in a patient with auditory agnosia due to bilateral lesions
      confined to the auditory radiations. A male patient experienced mild left
      temporal hemiplegia because of right putaminal hemorrhage at the age of 43 years.
      Thereafter he recovered completely but hypertension persisted. When he was 53
      years old, he suffered left putaminal hemorrhage and went into a coma. After
      recovering from the coma and right hemiplegia he could hear but could not
      discriminate speech sounds. Brain CT and MRI demonstrated small bilateral lesions
      confined to the auditory radiations. Magnetoencephalography demonstrated the
      disappearance of middle latency responses and auditory-evoked potential studies
      showed a very small Pa peak. In contrast, a positron emission tomography study
      demonstrated a marked increase in blood flow in the bilateral auditory cortex in
      response to both click and monosyllable stimuli. It is speculated that the
      auditory cortex receives functional projections from the cochlea via non-specific
      pathways in the cerebral hemispheres.

PMID- 16303687
TI  - Role of ciclosporin in steroid-responsive sudden sensorineural hearing loss.
AB  - CONCLUSIONS: A subgroup of patients with idiopathic sensorineural hearing loss
      (SNHL) will have steroid-dependent symptoms which can be confirmed using pure
      tone audiometry. Long-term treatment with high-dose corticosteroids exposes
      patients to potentially serious adverse effects. Immunosuppression with
      ciclosporin can be an effective and well-tolerated treatment for steroid
      responsive sudden SNHL. OBJECTIVE: To highlight ciclosporin as a therapeutic
      option in the treatment of steroid-responsive sudden SNHL. MATERIAL AND METHODS:
      A 39-year-old male with idiopathic sudden SNHL that was responsive to
      corticosteroids was treated with ciclosporin for 18 months. RESULTS: Steroid
      dependent SNHL was confirmed on audiological evaluation. Ciclosporin was
      administered, allowing corticosteroid therapy to be discontinued. Ciclosporin was
      effective at controlling all symptoms of SNHL. Remission was confirmed
      objectively with pure-tone audiometry.

PMID- 16303688
TI  - The global obesity epidemic: snacking and obesity may start with free meals
      during infant feeding.
AB  - Feeding is vital for survival. The brain has strong hunger and reward mechanisms
      that ensure optimal food intake for adequate nutrition. The drive for feeding is
      particularly strong in humans whose large brains require large energy support.
      This starts immediately after birth; the newborn child being able to taste
      sucrose and suck the sweet and fat from its mother's milk. At present, mothers
      are generally advised to breastfeed children as often as they like, which may be
      up to 15 times a day. At the same time, childhood obesity is rapidly developing.
      One reason for the rapidly increasing prevalence of childhood obesity may be
      overfeeding with snack food. CONCLUSION: We hypothesize that non-rule
      breastfeeding favours the development of snacking throughout the day during
      childhood, a habit which in turn favours the development of obesity.

PMID- 16303689
TI  - LC-PUFA content in human milk: is it always optimal?
AB  - The content of long-chain polyunsaturated fatty acids (LC-PUFAs) in human milk
      has been connected with infant growth and developmental indices. The LC-PUFA
      content of human milk usually reflects the dietary habits of mothers, so
      questions have been raised regarding the possibility of enriching maternal diet
      with LC-PUFAs during lactation (or even before) in order to improve infant
      outcome. Nevertheless, environmental and genetic factors have independent roles
      in affecting both maternal milk composition and infant development. CONCLUSION:
      Diet-related differences in the LC-PUFA composition of human milk are under
      active investigation for their possible contribution to infant development, but
      environment- and gene-related differences in both human milk composition and
      maternal diet should be considered in evaluating the adaptive mechanisms of
      infants and the effects of specific LC-PUFA dietary supplementations.

PMID- 16303690
TI  - When newborn infants are bound to die.
AB  - Withholding and withdrawing of intensive care of severely ill newborns may
      occasionally be needed when there is severe injury and extremely poor prognosis.
      In such cases, strict guidelines and procedures should be followed. In this issue
      of Acta Paediatrica, Arlettaz et al. describe such guidelines and report practice
      from the University Hospital in Zurich. To ensure an unbiased discussion, it is
      important that those who make decisions regularly receive input from external
      sources regarding indications of viability. This may be the case if, for
      instance, a unit has decided that the limit of viability is <26 wk, and many
      children with good life expectancy would in such units be denied intensive care.
      Does a liberal view on withholding or withdrawing treatment lead to poorer
      overall outcome results even for babies above the threshold of viability
      specified by the institution? CONCLUSION: Strict procedures should be followed in
      the case of withholding or withdrawing intensive care of severely ill newborn
      infants. In every institution, the indications for ending life should be
      discussed on a regular basis, preferably with external input. However, euthanasia
      of newborn infants is not compatible with Western cultural traditions and should
      be abandoned.

PMID- 16303691
TI  - A decreasing rate of neural tube defects following the recommendations for
      periconceptional folic acid supplementation.
AB  - BACKGROUND/AIM: Neural tube defects (NTDs) are the most common birth defects,
      resulting in severe mortality and morbidity. In 1995, the supplementation of
      folic acid periconceptionally was officially recommended in Germany. The impact
      of the recommendations on the rate of NTDs was assessed. METHODS: An active
      surveillance system was established in the northern Rhine area. From 1996, all
      departments of obstetrics were asked to report cases of NTDs in all abortions,
      live births and stillbirths. Compliance with the recommendations was evaluated in
      a sample of mothers who delivered at the Department of Obstetrics of Dusseldorf
      University in 2001. RESULTS: From 1996-2003, 520 NTDs were reported. Compared to
      the rate of NTDs in 1996 (10.5/10,000), the average incidence in the years 1997
      to 2003 dropped (6.8/10,000). The intake of folic acid, as recommended, was low
      among the general population (21.1%). CONCLUSION: Active surveillance data on the
      rate of NTDs are compatible with the maximum decrease of about 20% to be expected
      from data on the implementation of the recommendations. A much greater decrease
      in NTDs should be the challenge for the future.

PMID- 16303692
TI  - Long-chain polyunsaturated fatty acids in Chinese and Swedish mothers: diet,
      breast milk and infant growth.
AB  - Long-chain polyunsaturated fatty acids (LC-PUFAs) are essential dietary nutrients
      required for the optimal growth and development of infants, particularly of the
      brain and retina. It is important for exclusively breastfed infants to receive
      milk of a correct balance between omega-6 and omega-3 fatty acids. In this study,
      we compared the composition of LC-PUFAs in the diet and milk of mothers and their
      infants' growth between Chinese and Swedish. Twenty-three and 19 mother-term
      infant pairs from a rural area of northern Beijing, China, and Stockholm, Sweden,
      who were 3 mo old and exclusively breastfed, were studied. The Chinese diet was
      higher in carbohydrate (17% of energy) but lower in protein (4% of energy) and
      fat (12% of energy) than the Swedish diet. The intake of Chinese mothers
      contained more linoleic acid (LA, C(18 ratio 2 omega-6)) and less arachidonic
      acid (AA, C(20 ratio 4 omega-6)), eicosapentaenoic acid (EPA, C(20 ratio 5 omega
      3)) and docosahexaenoic acid (DHA, C(22 ratio 6 omega-3)) than that of Swedish
      mothers. The breast milk of the Chinese mothers had significantly higher LA and
      lower EPA and DHA levels than that of the Swedish mothers. However, in Chinese
      breast milk the AA level was significantly higher than that in Swedish breast
      milk. The recommended ranges of the ratios of LA to alpha-linolenic acid (LNA,
      C(18 ratio 3 omega-3)) and of AA to DHA in human milk are 5-10 and 0.5-1 compared
      with 23.0 and 3.1 in the Chinese breast milk, and 7.5 and 1.6 in the Swedish
      breast milk, respectively. CONCLUSION: The diet of the studied Chinese mothers is
      less balanced with regard to the levels of omega-6 and omega-3 polyunsaturated
      fatty acids (PUFAs) than that of the Swedish mothers, which is also mirrored in
      the breast milk of these mothers. The clinical relevance of the difference
      between the levels of LC-PUFAs in the breast milk of Chinese and Swedish mothers
      may be elucidated by a follow-up study of the cognitive and visual functions of
      the infants involved.

PMID- 16303693
TI  - Prevalence and risk factors for overweight and obesity in Portuguese children.
AB  - AIM: To identify risk factors for overweight and obesity in Portuguese children.
      METHODS: A cross-sectional study of children 7 to 9.5 y old was performed between
      October 2002 and June 2003. A total of 2,274 girls and 2,237 boys were observed.
      Weight and height were measured, and parents filled out a questionnaire about
      family characteristics. Overweight and obesity, using age- and sex-specific body
      mass index (BMI) cut-off points as defined by the International Obesity
      Taskforce, were used. RESULTS: After adjustment for age and sex, the odds ratio
      for childhood obesity increased by television viewing (reference 0-2 h; 2-3 h:
      1.51; 3-4 h: 1.72; 4 h: 1.63), paternal obesity (reference <18.5 kg/m(2); 25.0
      29.9: 3.06; 30.0: 7.09), maternal obesity (reference <18.5 kg/m(2); 25.0-29.9:
      9.06; 30.0: 18.13) and birthweight (reference <2,500 g; 2,500-3,000 g: 1.55;
      3,000-3,500 g: 1.87; 3,500-4,000 g: 2.13; 4,000 g: 2.74), and decreased by
      sleeping duration (reference 8 h/d; 9-10 h/d: 0.44; 11 h/d: 0.39), paternal
      education (reference primary school; secondary: 0.91; university: 0.42), maternal
      education (reference primary school; secondary: 1.13; university: 0.56), being a
      single child (reference yes; no: 0.56) and family size (reference one child; two
      children: 0.59; three children: 0.44; more than four children: 0.37). CONCLUSION:
      Our data support the perspective that education about energy intake and energy
      expenditure should be used much earlier in those families with high-risk
      children, namely those with high parental BMI or high birthweight. Protective
      factors were parental education and family size.

PMID- 16303694
TI  - Changes in shape and location of BMI distributions of Swedish children.
AB  - AIMS: One aim was to disentangle how the shape and location of the BMI
      distribution changed among Swedish children over a 12 y period. Another aim was
      to identify the age during childhood when changes occurred or became manifest.
      METHODS: Two population-based cohorts-2,591 children from Stockholm born 1985
      1987 and 3,650 from Gothenburg born 1973-1975-were compared with respect to BMI
      distributions from 2 to 15 y of age. RESULTS: Differences between the BMI
      distributions of the two cohorts were present from 5-6 y of age. From age 7, the
      children born in 1985-1987 and belonging to the upper parts of the BMI
      distribution, e.g. those above the 90th or 95th BMI percentiles, had much higher
      BMI mean values compared to their counterparts born 12 y earlier. Comparisons
      with respect to the 5th, 10th, 25th, 50th, 75th, 90th and 95th BMI percentiles
      showed that changes appeared above the 25th percentile and became increasingly
      pronounced in the upper parts of the BMI distributions. CONCLUSION: School-aged
      children in the rightmost parts of the BMI distributions may be more susceptible
      to "obesogenic" environmental exposures than those in the middle or leftmost
      parts. The results support the suggestion that the period of BMI rebound is
      critical for the development of obesity.

PMID- 16303695
TI  - New insights into juvenile parotitis.
AB  - AIM: We inquired about the possibility of a familial trend in juvenile parotitis
      and evaluated the role of SPINK1 mutations in juvenile parotitis. METHODS: The
      clinical records of all children admitted to the Helsinki University Hospital
      during 1995 to May 2003 because of swelling in the parotid gland were reviewed. A
      questionnaire on possible recurrences and on familial cases was mailed. As
      disturbances in trypsin inhibition might be involved in the pathogenesis, we
      assessed the SPINK1 gene encoding for Kazal-type trypsin inhibitor in voluntary
      patients. The study group comprised 133 children (boys 82 girls 51) with juvenile
      parotitis. The median age at presentation of first symptoms was 6.0 y (range 1-19
      y). RESULTS: Recurrent symptoms in the parotid gland were common (57%), and 29%
      of the children (38/133) had suffered from four or more episodes. A young age at
      the first episode of symptoms increased the likelihood of recurrences (p<0.0001).
      Familial cases of parotid swelling were common (22%; response rate 67%). A total
      of 47 patients (35%) agreed to testing for SPINK1 status. Four children had a
      major mutation (N34S or P55S), corresponding to an 8.5% (4/47) prevalence, but
      this was not different from the controls (5%). CONCLUSION: It is likely that
      inherited factors are involved in the manifestation of juvenile parotitis in a
      subset of patients. It is tempting to speculate that disturbed proteolytic
      balance may play a role in the development of symptoms.

PMID- 16303697
TI  - Iron supplements reduce erythrocyte copper-zinc superoxide dismutase activity in
      term, breastfed infants.
AB  - AIM: To investigate whether iron supplements compromise copper status in infants.
      METHODS: 214 healthy, term, breastfed Swedish and Honduran infants were
      randomized to (1) iron supplements (1 mg/kg/d) from 4-9 mo of age, (2) iron
      supplements from 6-9 mo, or (3) placebo. Blood samples were obtained at 4, 6, and
      9 mo and analyzed for plasma copper (p-Cu) and, at 9 mo, for copper/zinc
      dependent superoxide dismutase (CuZn-SOD) activity. RESULTS: P-Cu increased with
      infant age. At 9 mo, Honduran infants had significantly higher p-Cu (1.40+/-0.29
      vs 1.09+/-0.22 mg/l, p<0.001) and CuZn-SOD activity (1.09+/-0.29 vs 0.93+/-0.21
      U/mg Hb, p<0.001) than Swedish infants. Infants receiving iron supplements from 4
      9 mo had significantly lower CuZn-SOD at 9 mo of age (0.95+/-0.27 vs 1.08+/-0.24
      U/mg Hb, p=0.023) than those receiving placebo. CONCLUSION: There is a
      physiologic increase in p-Cu during the first 9 mo of life. Differences in copper
      status between Swedish and Honduran infants may be due to genetic or nutritional
      differences. Iron supplementation decreases CuZn-SOD activity, probably due to a
      negative effect on copper status. Possible clinical implications remain to be
      elucidated.

PMID- 16303696
TI  - Haematological parameters of HIV-1-uninfected infants born to HIV-1-infected
      mothers.
AB  - AIM: To investigate haematological parameters in infants born to HIV-1-infected
      mothers and exposed to combination antiretroviral therapy (ART) used to prevent
      mother-to-child transmission (MTCT). METHODS: A 2-y single-centre follow-up study
      performed in 109 infants born to HIV-1-positive mothers. Exclusion criteria for
      the infants were HIV-1 infection, perinatal death, or insufficient information.
      Haematological parameters of the remainder of 92 infants born to HIV-1-infected
      mothers and exposed to ART in utero and neonatally were compared with 75 matched
      non-ART-exposed children. RESULTS: Transmission rate of HIV-1 was 1.8% and
      occurred when the mother was not compliant with the treatment. In the HIV-1/ART
      exposed children there was a long-lasting reduction in absolute neutrophil counts
      (ANC) until at least 8 mo of age. According to PACTG toxicity scores, 16 infants
      were suffering from grade II or more (moderate-to-severe) toxicity of ART on ANC.
      In a multivariable analysis of maternal and neonatal risk factors, pregnancy
      duration was correlated with moderate-to-severe toxicity on ANC. There were no
      clinical implications detected, e.g. increased infections or antibiotic
      treatment. CONCLUSION: ART is successful in preventing MTCT, but alterations in
      haematological parameters may persist for a long period. The clinical
      implications remain uncertain. This suggestion increases the importance to
      continue prospective follow-up on the haematological parameters in ART/HIV
      exposed children.

PMID- 16303699
TI  - Sensory evoked potentials in infants with Down syndrome.
AB  - AIM: To investigate the sensory functions of the peripheral to central pathways
      in infants with Down syndrome (DS) by sensory evoked potentials. METHODS: Fifty
      five infants, 30 DS infants and 25 controls, were examined by multimodal evoked
      potentials, including brainstem auditory evoked potentials (BAEP), visual evoked
      potentials (VEP) and short-latency somatosensory evoked potentials (SSEP).
      RESULTS: No obvious difference was found in the peak latencies between the two
      groups for BAEP. Nine children with DS showed abnormal BAEP; six had hearing loss
      and three had prolonged wave I latencies. For VEP, the peak latencies of P(2) and
      N(2) were significantly longer and the amplitudes were smaller in the DS group
      than in the control group. Of the 30 infants with DS, five had significantly
      prolonged P(2) latencies and two had lower amplitudes. In SSEP, the mean
      latencies of N(20) and the interpeak latencies of N(13)-N(20) of the infants with
      DS showed apparent prolongation compared to the controls. Seven of 30 (23.3%) DS
      patients had prolonged N(20) latencies. CONCLUSION: Our results indicate that
      various sensory deficits occur in patients with DS during the first year of life.

PMID- 16303698
TI  - Graves' disease in children and adolescents: response to long-term treatment.
AB  - BACKGROUND: Optimal treatment of Graves' disease in paediatric patients is still
      a matter of controversy. Antithyroid drugs, radioiodine and thyroidectomy are the
      three therapeutic options available. AIM: To report our experience of long-term
      medical treatment and outcome of paediatric Graves' disease. METHODS: A 5-y-long
      medical protocol was implemented in 20 children and adolescents with Graves'
      disease. All patients received antithyroid drugs as the first therapeutic option;
      patients who did not enter long-term remission received I(131) and/or surgery as
      the definitive treatment. RESULTS: The mean age at diagnosis was 12.1+/-4 y. Only
      two patients were males, both presenting concomitant type 1 diabetes. Mean follow
      up was 13.8+/-5.5 y. Forty per cent of patients achieved long-term remission with
      low antithyroid drugs doses (mean treatment time: 5.4+/-1.4 y). Six patients
      received I(131) as definitive treatment and another six underwent surgery after
      completing medical treatment for 6.8+/-4.1 and 5.1+/-2 y, respectively. No
      patients requiring high antithyroid drugs doses to maintain euthyroidism reached
      long-term remission and needed I(131) and/or surgery. CONCLUSION: Implementation
      of a long-term antithyroid drug protocol achieved 40% long-term remissions in
      paediatric patients with Graves' disease. Need for maintained high doses of
      antithyroid drugs could be considered a predictive factor for no remission. When
      permanent remission was not obtained by medical treatment, I(131)and/or surgery
      allowed healing in all cases.

PMID- 16303700
TI  - Attention-deficit/hyperactivity disorder (ADHD) as a risk factor for persistent
      nocturnal enuresis in children: a two-year follow-up study.
AB  - AIMS: A previous prevalence study indicated that the prevalence of ADHD is highly
      increased in enuretic children. In the current 2-y follow-up study we investigate
      the relationship between both disorders further. Our goal is to determine whether
      the ADHD diagnoses can be reconfirmed and whether children with ADHD are more at
      risk for difficult-to-cure enuresis. Moreover, we explore the effect of medical
      enuresis parameters on the course of the voiding problem. METHODS: Eighty-six
      children with enuresis were screened twice on the presence of ADHD with a 2-y
      interval. A multi-method, multi-informant assessment of ADHD was used, the
      child's medical file was consulted, and a parent questionnaire on the child's
      current voiding problems was completed. RESULTS: Although 73% of all children
      with a 2-y-old diagnosis of ADHD still meet the disorder's criteria, only 66% of
      all subtype diagnoses can be reconfirmed. The odds that a child with ADHD still
      has voiding problems after 2 y are 3.17 times higher than for a child without
      ADHD. Although a slightly increased number of prescribed therapies in the ADHD
      group was noticed, no other significant differences in enuresis treatment methods
      were found between the groups. The medical parameters were not associated with
      treatment outcome. CONCLUSION: Since 73% of ADHD diagnoses can be reconfirmed,
      the data suggest that the prevalence of the ADHD syndrome rather than reactive
      ADHD symptomatology is increased in enuretic children. Children with ADHD are at
      risk for persistent enuresis. Two-year-old medical enuresis parameters seem to
      have little effect on the current presence/absence of enuresis.

PMID- 16303701
TI  - End-of-life decisions in delivery room and neonatal intensive care unit.
AB  - BACKGROUND: The increase in neonatal survival in recent decades has been followed
      by an increase in later disabilities. This has given rise to many new ethical
      issues. In different countries, efforts are being made to define ethical
      guidelines regarding withholding or withdrawing intensive care and end-of-life
      decisions in critically ill newborn infants. These guidelines have to be
      differentiated from ethical decision-making models which structure the process of
      decision making for an individual child. Such a framework has been in existence
      in our clinic for 10 years. AIM: The aims of this study were to evaluate how end
      of-life decisions are taken in our perinatal centre and to analyse whether these
      decisions are consistent with our framework for structured ethical decision
      making. METHODS: 199 consecutive neonatal deaths over 5 y were evaluated.
      RESULTS: In 157 cases (79%), end-of-life decisions were taken according to our
      ethical framework; in the remaining 42 cases (21%), the baby died before this
      could be done. In 92% of cases, parents were involved in the decision and, in all
      cases but one, agreed with the decision. A patient's life was never intentionally
      and actively terminated. CONCLUSION: In contrast to earlier years, in-hospital
      death in our clinic is nowadays usually preceded by structured and documented
      medical end-of-life decisions.

PMID- 16303702
TI  - Does chronic prenatal Doppler pathology predict feeding difficulties in neonates?
AB  - AIM: To determine whether infants with compromised fetomaternal circulation, but
      not yet critically threatened by absent end-diastolic flow velocities in the
      umbilical arteries, are at a risk for feeding problems. METHODS: In a
      retrospective case-control study, enteral feeding and clinical data were compared
      between infants with decreased prenatal end-diastolic umbilical flow velocity
      (DEDFV) or brain-sparing pathology and controls matched for gestational age (GA).
      In all infants, enteral feedings were advanced according to a standardized
      enteral feeding protocol. RESULTS: 11 (GA>34 wk) of the 87 infants with DEDFV
      were fully enterally fed by day 5 and excluded, leaving 76 infants (and matched
      controls) for final analysis. DEDFV infants were significantly smaller (1,230+/
      550 g vs 1,600+/-682 g). Advancement of enteral feedings varied widely, with a
      significant difference between DEDFV infants and controls. There was no
      difference in the incidence of NEC (five in both groups). In the most severely
      affected subgroup of 25 infants with GA<30 wk and prenatal brain sparing, enteral
      feedings were significantly delayed in comparison to the controls (parenteral
      amino acid administration for 22 vs 15 d; significantly fewer enteral calories
      through day 15). CONCLUSION: Enteral feeds were introduced more slowly to infants
      who had shown signs of prenatal distress with brain sparing. However, a
      predisposition to NEC could not be proven. Our results thus do not support the
      delay of enteral feedings based on prenatal Doppler pathology.

PMID- 16303703
TI  - Troponin-T levels in perinatally asphyxiated infants during the first 15 days of
      life.
AB  - AIM: To measure serial cardiac troponin-T, creatine kinase, creatine kinase-MB,
      aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase
      levels in asphyxiated newborn infants during the first 15 d of life. METHODS:
      Troponin-T, creatine kinase, creatine kinase-MB, aspartate aminotransferase,
      alanine aminotransferase and lactate dehydrogenase (LDH) concentrations were
      measured prospectively in blood samples obtained from 45 asphyxiated and 15
      healthy term neonates within the first 2-4 h, third, seventh and 15th days.
      RESULTS: Infants with severe asphyxia had significantly higher cardiac troponin-T
      levels than grade I and II asphyxiated and healthy neonates within the first 2-4
      h of life (0.34+/-0.21 ag/ml vs 0.07+/-0.03 ag/ml, 0.12+/-0.07 ag/ml, 0.04+/-0.02
      ag/ml, respectively). Troponin-T levels remained high on days 3 and 7 in severely
      asphyxiated neonates. The creatinine kinase-MB levels were significantly higher
      in grade II and III asphyxiated neonates than grade I asphyxiated and healthy
      neonates within the first 2-4 h. No difference was found in creatinine kinase-MB
      on day 3. There was cardiac involvement in 12 (80%) newborns of group III on B
      mode echocardiographic images on day 1. However, no echocardigraphic pathology
      was found in the seventh- and 15th-day echocardiographic analysis in any groups.
      CONCLUSION: Our results suggest that asphyxia-related cardiac changes were
      significant but reversible in severely asphyxiated neonates, and troponin T is a
      good determinant of the degree of injury to the heart within the first week of
      life. Cardiac troponin T also has a wider diagnostic frame than other diagnostic
      markers of myocardial damage.

PMID- 16303706
TI  - Breastfeeding and school achievement in Brazilian adolescents.
AB  - AIM: To assess the effect of breastfeeding duration on school achievement in a
      Brazilian cohort. METHODS: In a population-based birth cohort, we analysed the
      highest grade achieved in school of over 2,000 male 18-y-olds relative to
      breastfeeding information collected in early life. Analyses were adjusted for
      birthweight, family income, maternal and paternal schooling, household assets,
      number of siblings, social class, maternal smoking during pregnancy, and
      ethnicity. RESULTS: After adjustment for confounding variables, there was a
      highly significant trend in school achievement with increasing breastfeeding
      duration. Those breastfed for 9 mo or more were ahead by 0.5-0.8 school grades,
      relative to those breastfed for less than 1 mo. Data from a cross-sectional
      survey in the same population suggest that such a difference corresponds to a 10
      15% difference in adult income levels. The duration of exclusive or predominant
      breastfeeding was also positively associated with schooling. CONCLUSION: Unlike
      studies from developed countries, there was no clear association between
      breastfeeding duration and either the family's socio-economic level or parental
      schooling in our sample and therefore residual confounding is improbable. These
      results suggest that the impact of breastfeeding on intellectual development may
      lead to sizeable differences in adult education and wage-earning performance.

PMID- 16303704
TI  - Clinical features of nosocomial infections by extended-spectrum beta-lactamase
      producing Enterobacteriaceae in neonatal intensive care units.
AB  - AIM: To determine the risk factors for the acquisition of nosocomial extended
      spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae infection in infants
      hospitalized in neonatal intensive care units (NICUs) and to evaluate the
      therapeutic outcome of these infants. METHODS: We retrospectively reviewed the
      medical records of infants with nosocomial ESBL-producing Enterobacteriaceae
      infection hospitalized in NICUs at Chang Gung Children's Hospital in 2001. The
      clinical features of these infants were compared with a cohort of non-ESBL
      producing Enterobacteriaceae-infected infants during the same period. The
      therapeutic outcome of the infants in the ESBL group was analysed. RESULTS:
      Seventy infants were included in this study. Thirty-one infants with 34 isolates
      were identified in the ESBL group and 39 infants with 42 isolates in the non-ESBL
      group. Of the parameters analysed, including gestational age, birthweight, length
      of hospital stay before onset, the number of antibiotics used, the duration of
      third-generation cephalosporin usage and the number of patients receiving a third
      generation cephalosporin prior to the onset of infection, no significant
      difference was found between the two groups. The infection-contributed case
      fatality rate was 3.0% (1 of 33) in the ESBL group, not significantly different
      from that in the non-ESBL group (1 of 41, 2.4%). Of the 31 patients in the ESBL
      group, 18 were treated with a carbapenem as definitive therapy while 13 were
      treated with a non-carbapenem antibiotic regimen. No significant difference was
      noted in terms of mortality rate between the two subgroups. CONCLUSION: The
      outcome of the infants hospitalized in the NICU with ESBL-producing
      enterobacterial infections was not indispensably grave, even when treated with a
      non-carbapenem antibiotic regimen. The risk factors for the acquisition of ESBL
      producing enterobacterial infections in these infants were not identified in this
      series.

PMID- 16303705
TI  - Crystalloid or colloid for partial exchange transfusion in neonatal polycythemia:
      a systematic review and meta-analysis.
AB  - AIMS: To determine whether crystalloid solutions are as effective as colloid
      solutions when a partial exchange transfusion is performed in newborns with
      polycythemia. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Controlled
      Trials Register of the Cochrane Library (1966-2004). Keywords used were:
      polycythemia, partial exchange transfusion, hyperviscosity, and limited to
      newborn. Randomized studies in newborns with polycythemia were selected for
      evaluation. Outcomes examined were: long-term neurodevelopment; short-term
      physiological effects; improvement in clinical symptoms; reduction in haematocrit
      at 4-6 h; haematocrit at 24 h; and frequency of serious complications. RESULTS:
      Four randomized controlled clinical trials, including 200 patients in total, with
      evaluable data, which satisfied our criteria, were found. There were no data on
      long-term outcomes. There is no reported important difference in short-term
      physiologic effects. Use of crystalloid was as effective as colloid in both
      correction of haematological values and reduction of clinical symptoms following
      partial exchange transfusion. CONCLUSION: Crystalloid solutions are as effective
      as colloid solutions for partial exchange transfusion. When crystalloid solutions
      are used for this purpose, there is no risk of transmission of blood-borne
      diseases, there is no risk of anaphylaxis, they are rapidly and easily available,
      and are less expensive. The use of crystalloid should become the standard for
      partial exchange transfusion.

PMID- 16303707
TI  - Comparison between Japanese and Swedish schoolchildren in regards to physical
      symptoms and psychiatric complaints.
AB  - BACKGROUND: Physical symptoms are an increasing problem among Japanese children
      and adolescents, and the symptoms seem to be related to their school situation.
      These symptoms are prevalent in Sweden, and a comparison with Japan is of
      interest due to the differences in the educational system and school climate.
      OBJECTIVE AND METHODS: To compare physical symptoms and psychiatric complaints in
      school pupils from Japan and Sweden, using a questionnaire that also addressed
      life satisfaction and stressful life events. The study population comprised 742
      Japanese children and 1,120 Swedish children attending public compulsory schools,
      grades 4-9 (10-15 y). Physical symptom and psychiatric complaint scores were
      calculated for each pupil. RESULTS: The Japanese children had significantly
      higher physical symptom and psychiatric complaint scores than did the Swedish
      children. Both the physical symptom and psychiatric complaint scores were
      significantly higher in adolescents than in preadolescents in Japan; this trend
      was less apparent in Swedish children. In addition, Japanese children were found
      to have considerably lower life satisfaction. Loss of appetite was the only
      physical symptom more prevalent in the Swedish population compared to the
      Japanese population. CONCLUSION: We conclude that Japanese schoolchildren have
      more physical symptoms and psychiatric complaints and less life satisfaction than
      Swedish schoolchildren of corresponding ages.

PMID- 16303708
TI  - The effect of voluntary dehydration on cognitive functions of elementary school
      children.
AB  - AIMS: (1) To describe the occurrence of voluntary dehydration in two classes of
      elementary school students as expressed by their morning and noon-time urine
      osmolality; and (2) to determine the relationship between the children's scores
      on cognitive tests and their state of hydration. METHODS: Group comparison among
      fifty-eight sixth-grade students (age range 10.1-12.4 y old) during mid-June at
      two schools in a desert town. Morning and noon-time urine samples were collected
      in school, and five cognitive tests were scored in the morning and at noon-time.
      MAIN OUTCOME MEASURES: (1) morning and noon-time urine osmolality; (2) scores of
      five cognitive tests (hidden figures, auditory number span, making groups, verbal
      analogies, and number addition) that were applied in the morning and at noon
      time. RESULTS: Thirty-two students were dehydrated (urine osmolality above 800
      mosm/kg H(2)O) in the morning. An individual's noon-time urine osmolality was
      highly related to morning osmolality (r=0.67, p=0.000). The morning cognitive
      scores were similar in the hydrated and dehydrated students (p=0.443). The
      adjusted mean scores of the noon-time tests, with the morning test scores as
      covariates, demonstrated an overall positive trend in four of the five tests in
      favor of the hydrated group (p=0.025). The effect was mainly due to the auditory
      number span test (p=0.024). CONCLUSION: Voluntary dehydration is a common
      phenomenon in school-aged children that adversely affects cognitive functions.

PMID- 16303709
TI  - Risk factors for delayed discharge home in very-low-birthweight infants:- a
      population-based study.
AB  - AIM: To identify risk factors for delayed discharge home in a population-based
      cohort of very-low-birthweight (VLBW) infants. METHODS: Demographic, pregnancy,
      perinatal, and neonatal data were collected in a national population-based
      database on VLBW infants born from 1995 through 2002. Multivariate analysis
      determined association with delayed discharge (discharge at a postmenstrual age
      >42 completed weeks). RESULTS: 882 infants with delayed discharge comprised 9.4%
      of survivors but accounted for 19.8% of total hospital days utilized until
      discharge home. Infants with delayed discharge compared to those discharged by
      term were born at an earlier mean gestational age, at a lower mean birthweight,
      and had a longer mean hospital stay. Delayed discharge was independently
      associated with decreasing birthweight (OR 1.25, 95% CI 1.19, 1.31), congenital
      anomalies (OR 4.80, 95% CI 3.66, 6.28), bronchopulmonary dysplasia (OR 5.88, 95%
      CI 4.60, 7.57), intraventricular hemorrhage grades 3-4 (OR 1.78, 95% CI 1.34,
      2.36), sepsis (OR 1.87, 95% CI 1.54, 2.26), and surgically treated necrotizing
      enterocolitis (OR 20.20, 95% CI 12.85, 32.03). CONCLUSION: VLBW infants with
      congenital anomalies or severe complications of preterm birth are at increased
      risk for delayed discharge home. Early identification of these infants may enable
      interventions aimed at reducing the detrimental effects of prolonged
      hospitalization and promoting optimal transition from the hospital to the home
      environment.

PMID- 16303710
TI  - Doxapram and developmental delay at 12 months in children born extremely preterm.
AB  - AIM: To examine the relation of doxapram to a developmental score achieved by a
      structured telephone interview in a group of extremely-preterm-born children.
      METHODS: Parents of 88 children born extremely preterm were contacted by
      telephone and interviewed by a structured questionnaire (R-PDQ) when the
      corrected age of their child was 9-15 mo. RESULTS: We found that doxapram
      treatment was associated with a deficit in age-adjusted R-PDQ score. CONCLUSION:
      Doxapram may have a negative effect on neurodevelopmental outcome.

PMID- 16303711
TI  - Anthropometry at the time of diagnosis in Danish children with inflammatory bowel
      disease.
AB  - All patients below 15 y of age living in the eastern part of Denmark with a
      diagnosis of inflammatory bowel disease (IBD) during the period 1998-2000 were
      identified (n=94) and anthropometrical data at the time of diagnosis were
      evaluated. CONCLUSION: The height-for-age and the BMI-for-age, as evaluated by z
      scores, of children with ulcerative colitis (UC) did not differ from those of
      normal Danish children, but Crohn's disease (CD) children had significantly lower
      height and BMI values, both when compared to normal children and children with
      UC. In contrast to UC, CD is frequently complicated by malnutrition and growth
      retardation at the time of diagnosis.

PMID- 16303712
TI  - Outpatient treatment with corticosteroids and antibiotics for acalculous
      cholecystitis in chronic granulomatous disease.
AB  - We report the outpatient management of acalculous colecistitis in an 18-y-old
      male with X-linked chronic granulomatous disease. The patient complained of
      abdominal pain and the initial ultrasound showed a gallbladder with a thickened
      wall. CONCLUSION: In chronic granulomatous disease, pain from a thickened
      gallbladder disappears after oral treatment with glucocorticoids and antibiotics.

PMID- 16303713
TI  - Usefulness of pancreatic ultrasonography in the diagnosis of Shwachman-Bodian
      Diamond syndrome.
AB  - AIM: To evaluate the usefulness of pancreatic ultrasonography in diagnosing
      Shwachman-Bodian-Diamond syndrome (SBDS). METHODS: Diagnostic methods in two
      infants with SBDS were retrospectively reviewed. RESULTS: Patient 1 first
      presented with hepatic steatosis in the early infantile period, and later
      developed myelodysplastic syndrome. Patient 2 presented with frequent infections
      and elevated liver function tests without any haematological alterations. Both
      patients were considered to have impaired exocrine pancreatic function. Abdominal
      ultrasonography (US) obtained at 9 mo for patient 1 and at 10 mo for patient 2
      showed diffuse high echogenicity, which raised suspicions of SBDS. SBDS gene
      analysis confirmed SBDS in both patients. CONCLUSION: Pancreatic US is sensitive
      in detecting pathological change in SBDS patients. It should be applied to the
      diagnostic approach for patients who show only minor signs of SBDS.

PMID- 16303714
TI  - Perinatal management of a preterm neonate affected by hyperprostaglandin E2
      syndrome (HPS).
AB  - BACKGROUND: Neonates affected by hyperprostaglandin E(2) syndrome (HPS) present
      with severe polyuria. Both urinary losses as well as prostaglandin synthesis
      inhibitors may precipitate acute renal failure (ARF). AIM: Our goal was to
      maintain euvolaemia by replacement of urinary losses. PATIENT: Our patient was
      born prematurely with a family history typical of HPS. Urinary salt and water
      losses and PGE(2) excretion were determined in 2- to 4-h intervals. Salt and
      water were replaced accordingly. RESULTS: Within the first 48 h, urinary losses
      and PGE(2) increased continuously to 50 ml/kg/h and 374 ng/h/1.73 m(2),
      respectively. Following exposure to 0.05-0.5 mg/kg/d indomethacin, urinary output
      decreased steadily to 10-15/ml/kg/h. CONCLUSION: In euvolaemic preterm neonates
      with HPS and the need for excessive replacement of salt and water, inhibition of
      renal PGE(2) excretion with indomethacin effectively reduces polyuria and
      natriuresis without acutely compromising renal function.

PMID- 16303715
TI  - The association of Kawasaki disease with syndrome of inappropriate secretion of
      antidiuretic hormone is questionable.

PMID- 16303718
TI  - Endoluminal pelvic perfusion with norepinephrine causes only minor systemic
      effects and diminishes the increase in pelvic pressure caused by perfusion.
AB  - OBJECTIVE: To evaluate the effect of endoluminal norepinephrine (NE) on transport
      pressures of the normal upper urinary tract of the pig and on plasma levels of NE
      in relation to possible systemic effects. MATERIAL AND METHODS: Six anaesthetized
      pigs weighing approximately 39 kg were studied. Transparenchymally, two 6-F
      catheters were introduced into the renal pelvis bilaterally to measure pressure
      and perfusion. Ultrasonic flow probes recorded renal arterial blood flow, and a
      transurethral 10-F catheter drained the bladder and monitored diuresis. In all
      six animals, the bilateral pelvic pressure response was examined at increasing
      perfusion rates (2, 4, 6, 8, 10 and 15 ml/min) and with increasing doses of NE
      (0, 5, 50 and 100 microg/ml). Arterial blood samples were analysed for NE,
      epinephrine and blood glucose. The systemic blood pressure, heart rate and
      electrocardiogram were registered. RESULTS: At all the investigated
      concentrations, endoluminal NE significantly diminished the increase in pelvic
      pressure caused by pelvic perfusion at all flow rates. At the lowest
      concentration of NE, no significant increase in the plasma level of NE was
      observed and the blood pressure did not increase. During perfusion with 50 and
      100 microg/ml NE, plasma levels of NE increased significantly from 487+/-398 to
      1798+/-910 and 2961+/-2093 pg/ml, respectively. This was accompanied by
      significant rises in mean systolic blood pressure from a baseline value of 95+/
      10 mmHg to 111+/-20 and 118+/-23 mmHg, respectively. Heart rate, renal arterial
      blood flow and plasma levels of epinephrine and glucose did not change.
      CONCLUSIONS: Endoluminal NE diminished the increase in pelvic pressure caused by
      pelvic perfusion even at concentrations too low to cause significant changes in
      NE plasma levels or systemic effects. Very high NE concentrations in the
      perfusion fluid caused increased plasma levels and a modest but significant
      increase in blood pressure. Administration of endoluminal NE may be useful in
      upper urinary tract stone treatment and endoscopy.

PMID- 16303719
TI  - Comparison of tumor- and comorbidity-related predictors of mortality after
      radical prostatectomy.
AB  - OBJECTIVES: To identify and compare tumor- and non-tumor-related predictors of
      survival after radical prostatectomy and to incorporate the latter into the tumor
      node metastasis classification of prostate cancer. MATERIAL AND METHODS: A total
      of 402 patients who underwent radical prostatectomy (mean follow-up period 6.9
      years) were stratified according to postoperative tumor stage, Gleason score,
      prostate-specific antigen level, age and five comorbidity classifications. Cox
      proportional hazard models were used to identify independent prognostic factors
      predicting overall survival. RESULTS: Comorbidity (American Society of
      Anesthesiologists Physical Status classification), Gleason score and age, but not
      tumor stage, were independent predictors of overall survival. Based on tumor
      stage and the identified independent prognostic factors, an easily applicable
      prognostic score was developed to predict overall mortality. CONCLUSION: A
      prognostic classification of radical prostatectomy patients based on Gleason
      score, comorbidity and age and supplementary to a coarsened variant of the tumor
      node metastasis classification may be of clinical value.

PMID- 16303720
TI  - Prostate cancer with small-cell morphology: an immunophenotypic subdivision.
AB  - OBJECTIVE: To study the immunophenotypic characteristics and clinical outcome of
      morphologically undifferentiated prostatic carcinoma with small-cell morphology
      (U-PC-SCM). MATERIAL AND METHODS: Sixteen patients with U-PC-SCM were enrolled.
      The streptavidin-biotin complex immunohistochemical method was used on paraffin
      embedded tissue sections to test positivity for prostate-specific antigen,
      prostate-specific acid phosphatase, CD57, androgen receptors, CK8-18, epithelial
      membrane antigen, carcinoembryonic antigen, CD56, neuron-specific enolase,
      chromogranin, synaptophysin, serotonin, various hormones, thyroid transcriptional
      factor-1 and Ki-67/MIB1. RESULTS: Based on immunophenotypic criteria, we
      identified two groups of patients. The final diagnosis was U-PC (Gleason score
      10) in Group 1 (n=9) and pure or mixed neuroendocrine small-cell carcinoma in
      Group 2 (n=7). Group 1 underwent total androgen blockade (TAB) with no major
      response and had a median survival of 9 months. In Group 2, three patients
      underwent TAB, two of whom died of progressive disease. The third patient showed
      a partial response (PR) for 18 months but eventually relapsed with liver
      metastatic lesions. He was then treated with cisplatin + etoposide and showed a
      PR for 3 months and survived for 5 months after the initiation of the second-line
      chemotherapy (CTH) treatment. The other four patients received six cycles of
      cisplatin + etoposide. There were two complete responses of >14 and >22 months,
      respectively and 2 PRs of 11 and 17 months, respectively, the partial responders
      surviving for 14 and 21 months, respectively. CONCLUSION: U-PC-SCM with a
      neuroendocrine immunophenotype is a histogenetically distinct entity with
      different clinical and laboratory manifestations which responds well to a
      cisplatin + etoposide CTH regimen.

PMID- 16303721
TI  - Subcapsular versus total orchiectomy in the treatment of advanced prostate
      cancer: a randomized trial.
AB  - OBJECTIVE: To compare subcapsular and total orchiectomy in patients with advanced
      prostate cancer. MATERIAL AND METHODS: Two urological centers participated in a
      prospective, randomized study comparing complication rates and patient
      satisfaction. A total of 89 patients were randomized to either total or
      subcapsular orchiectomy. After the operation the patients were scheduled for a 3
      month follow-up visit and subsequently followed the routine of the clinic. Three
      men dropped out of the study and thus 86 were evaluated. RESULTS: The number of
      postoperative complications differed significantly between the two groups: 14/46
      in the total and 5/40 in the subcapsular orchiectomy patients. Complications were
      defined as reoperation or a postoperative complication causing additional
      ambulatory visits during the first 3 months postoperatively. Eight patients were
      reoperated on: 6/46 in the total and 2/40 in the subcapsular orchiectomy group,
      and this difference was not statistically significant. There was no significant
      difference in complication rates among trained urologists and trainees or among
      patients who received local or general anesthesia. CONCLUSION: Subcapsular
      orchiectomy is associated with significantly fewer postoperative complications
      than total orchiectomy.

PMID- 16303722
TI  - Continent cutaneous urinary diversion is still a valid alternative after
      cystectomy for bladder carcinoma.
AB  - OBJECTIVE: We compared patient opinions concerning reservoir/bladder function as
      well as quality of life (QOL) after cystectomy for bladder carcinoma and
      continent cutaneous urinary diversion or orthotopic bladder reconstruction.
      MATERIAL AND METHODS: Fifteen patients with Kock reservoirs (11 females, 4 males)
      and 11 men with orthotopic bladders answered the European Organization for
      Research and Treatment of Cancer quality-of-life questionnaire-C30 as well as
      specially constructed questions concerning reservoir/bladder function. The
      glomerular filtration rate (GFR) was determined using Cr-EDTA or iohexol
      clearance. RESULTS: Functioning and global health/QOL scales did not differ
      between the two groups of operated patients or between diverted patients and
      gender- and age-matched groups from the general population. The majority of the
      patients were satisfied/very satisfied with their diversion but more patients
      were troubled by leakage in the orthotopic bladder group than in the Kock
      reservoir group. The GFR was similar in the two groups. CONCLUSION: Continent
      cutaneous urinary diversion is associated with fewer leakage problems than
      orthotopic bladder reconstruction after cystectomy for bladder carcinoma.

PMID- 16303723
TI  - Diuretic treatment of nocturnal enuresis.
AB  - OBJECTIVE: Nocturnal polyuria is considered a major pathogenetic factor in
      nocturnal enuresis, and the antidiuretic drug desmopressin, given at bed-time, is
      consequently recognized as a first-line treatment alternative. The aim of this
      open, non-randomized study was to see whether diuretic medication, given in the
      afternoon, could give similar therapeutic benefit. MATERIAL AND METHODS: Sixty
      three children suffering from primary, monosymptomatic, nocturnal enuresis were
      included in the study by their primary care paediatrician. After 14 days without
      any treatment and 14 days for which 0.4 mg of desmopressin was given orally at
      bed-time, the children were given furosemide 1 mg/kg in the afternoon for 14
      consecutive days. The numbers of wet and dry nights were recorded. RESULTS: The
      numbers of wet nights at baseline, during desmopressin treatment and during
      furosemide treatment were 10.2+/-3.5, 6.4+/-4.6 and 8.2+/-4.5, respectively. Both
      drugs were significantly better than no treatment, but only a small proportion of
      patients became completely dry: 24% on desmopressin and 12% on furosemide.
      Desmopressin was significantly better than furosemide. Three children who showed
      no therapeutic effect on desmopressin treatment had a favourable response to
      furosemide. CONCLUSION: Furosemide, given in the afternoon, has minor therapeutic
      potential in nocturnal enuresis.

PMID- 16303724
TI  - Mycoplasmas in semen of chronic prostatitis patients.
AB  - OBJECTIVE: To evaluate the occurrence of mycoplasmas in the semen of chronic
      prostatitis patients. MATERIAL AND METHODS: Genital mycoplasmas (Mycoplasma
      hominis, Mycoplasma genitalium, Ureaplasma urealyticum, Ureaplasma parvum) were
      sought in the semen of 121 chronic prostatitis patients [38 National Institutes
      of Health (NIH) category IIIa, 59 NIH category IIIb and 24 NIH category IV] and
      40 controls. The commercially available kit Mycoplasma IST was applied to the
      semen samples of all 161 men, and polymerase chain reaction (PCR) to those of 60
      randomly selected men. RESULTS: Ureaplasmas were found in all study groups (at
      frequencies ranging from 12% to 25%) using the Mycoplasma IST test, but M.
      hominis was found only in one NIH category IIIb patient. Using PCR, most of the
      ureaplasmas appeared to be U. parvum, which was found in all prostatitis groups
      (18% of NIH category IIIa, 15% of NIH category IIIb and 25% of NIH category IV
      patients) but not in the controls. M. genitalium was found in 18% of the NIH
      category IIIa patients. All of the mycoplasmas occurred significantly more
      frequently in prostatitis patients than in controls and in NIH category IIIa
      patients than in controls. CONCLUSION: Mycoplasmas occur more frequently in the
      semen of prostatitis patients than in that of healthy controls, with U. parvum
      being the most frequently occurring species.

PMID- 16303725
TI  - Renal concentrating capacity in female outpatients with symptomatic urinary tract
      infection.
AB  - OBJECTIVE: Renal concentrating capacity (RCC) has been used as a tool in the
      diagnosis of the site of urinary tract infection (UTI). In this study, RCC was
      measured in women with symptoms of UTI in relation to the clinical picture and
      the bacterial species isolated. MATERIAL AND METHODS: In 633 outpatients aged >
      or =18 years with symptoms of UTI, a renal concentration test with desmopressin
      was performed at baseline. The test was repeated after antibiotic treatment in a
      subset of patients with osmolality values below the reference levels at entry.
      The bacterial species were identified and patients were classified as having
      either pyelonephritis or cystitis. RESULTS: RCC was reduced in patients infected
      with Escherichia coli or Staphylococcus saprophyticus compared to those who had
      negative urine cultures and increased after antibiotic treatment. Patients with
      symptoms of both pyelonephritis and cystitis had reduced RCC: 44/68 (65%) and
      205/457 (45%), respectively. CONCLUSIONS: These findings demonstrate a
      considerable overlap in RCC between patients with pyelonephritis and cystitis,
      making the osmolality test unreliable for the purpose of diagnosis of the site of
      UTI.

PMID- 16303726
TI  - Success rates after shock-wave lithotripsy: do congenital anomalies of the
      kidneys really decrease stone clearance rates?

PMID- 16303727
TI  - Reliability testing of the Danish version of the Kidney Disease Quality of Life
      Short Form.
AB  - OBJECTIVE: The questionnaire Kidney Disease Quality of Life Short Form version
      1.3 (KDQOL-SF) is valuable for assessing the health-related quality of life in
      patients treated with chronic dialysis. The aim of this study was to translate
      and test the reliability of the KDQOL-SF for use in Denmark. MATERIAL AND
      METHODS: Translation into Danish and back-translation into English were
      performed. Pilot, field and internal consistency reliability tests were
      performed. RESULTS: Cronbach's alpha coefficients for the internal reliability
      test ranged from 0.77 to 0.93 for the eight generic scales. In a test involving
      all patients, two of the disease-specific scales had Cronbach's alpha
      coefficients of <0.70 ("social support" = 0.67; and "quality of social
      interaction" = 0.43). After removing one item from the scale "quality of social
      interaction", Cronbach's alpha reached 0.63. A test of the scores of peritoneal
      dialysis (PD) patients discovered low reliability for three disease-specific
      scales. The KDQOL-SF manual and the Danish manual for the Short Form 36 (SF36)
      differed in the scoring of four generic scales: "role limitation-physical",
      "bodily pain", "general health" and "social function". CONCLUSIONS: With the
      exception of the scale "quality of social interaction" the Danish translation of
      the KDQOL-SF achieved values in the internal consistency reliability test of the
      same level as the original U.S. version. When data were stratified according to
      dialysis treatment, the reliability of PD patients scores was lower. Generic data
      from the questionnaire SF36 should be scored according to the Danish SF36 manual.

PMID- 16303728
TI  - Safety and efficacy of atorvastatin in patients with severe renal dysfunction.
AB  - OBJECTIVE: To investigate the efficacy and safety of a daily dose of 10 mg of
      atorvastatin in patients with chronic kidney disease (CKD) stages 4 and 5 and a
      glomerular filtration rate of <30 ml/min. MATERIAL AND METHODS: This was an open,
      prospective, randomized study. A total of 143 patients were included: 73 were
      controls and 70 were prescribed 10 mg/day of atorvastatin. As efficacy variables,
      total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density
      lipoprotein (HDL) cholesterol and triglyceride levels were determined at the
      start of the study and at 1, 3, 6, 12, 18, 24, 30 and 36 months. RESULTS: The
      follow-up period was a mean of 20+/-14.4 months (range 1-36 months) for those on
      atorvastatin versus 22+/-12.7 months (range 0.5-36 months) for the controls.
      Compared with baseline values, patients treated with atorvastatin had
      significantly lower concentrations of total cholesterol at Month 36 (5.8 vs 4.4
      mmol/l; -23%; p<0.001), of LDL cholesterol at Month 36 (3.6 vs 2.2 mmol/l; -35%;
      p<0.001) and of triglycerides at Months 24 (2.5 vs 1.9 mmol/l) and 36 (2.5 vs 1.8
      mmol/l). The controls had significantly reduced levels of total cholesterol at
      Month 36 (p<0.21) and of LDL cholesterol at Months 30 and 36. Compared with the
      controls, the atorvastatin group had lower levels of total cholesterol and LDL
      cholesterol at Months 1-30. Fifteen patients (21%) stopped taking their
      medication as they could not tolerate the side-effects, the most frequent
      complaints being gastrointestinal discomfort and headache. CONCLUSION: Although
      the medication caused no severe adverse events, we recommend caution when using
      atorvastatin for severe CKD patients until further evidence of its safety and
      efficacy is verified.

PMID- 16303729
TI  - Low-dose dual blockade of the renin-angiotensin system improves tubular status in
      non-diabetic proteinuric patients.
AB  - OBJECTIVE: Treatment with agents that inhibit the renin-angiotensin system is
      commonly regarded as a gold standard renoprotective strategy in patients with
      chronic kidney diseases. For maximum antiproteinuric effect, the dose titration
      of these agents is recommended. This therapeutic strategy is not used for
      proteinuric patients who are not able to receive high doses of angiotensin
      converting enzyme inhibitor or angiotensin II receptor antagonists. MATERIAL AND
      METHODS: In patients with primary glomerulonephritis (n=24), a randomized, triple
      treatment, triple-period, cross-over study was performed to compare the effects
      of combined therapy with benazepril 5 mg and losartan 25 mg and monotherapy with
      either agent alone at a two-fold higher dose on the extent of tubular injury as
      assessed by alpha1-microglobulin (alpha1-m) excretion and the plasma level of
      transforming growth factor-beta1 (TGF-beta1). RESULTS: Combination therapy
      significantly reduced alpha1-m excretion compared to either agent used alone:
      178.29+/-27.36 to 99.63+/-13.03 mg/g creatinine for losartan + benazepril vs
      178.29+/-27.36 to 161.59+/-23.22 mg/g creatinine for benazepril alone (p<0.05;
      ANOVA) and 178.29+/-27.36 to 99.63+/-13.03 mg/g creatinine for losartan +
      benazepril vs 178.29+/-27.36 to 173.45+/-27.69 mg/g creatinine for losartan alone
      (p<0.05; ANOVA). There was a significant correlation between change in alpha1-m
      excretion and reduction in proteinuria (r=0.704; p=0.023). There were no
      differences in TGF-beta1 level between the studied treatments. Systemic blood
      pressure reduction did not differ among the therapies. CONCLUSIONS: Combination
      therapy with angiotensin-converting enzyme inhibitor and angiotensin II subtype 1
      receptor antagonists at very small doses may be superior to monotherapy with
      these agents at higher doses as far as tubular injury is concerned. We speculate
      that such a therapeutic strategy may be a useful approach for patients who are
      known not to be capable of receiving optimal renoprotective doses of these
      regimens.

PMID- 16303730
TI  - Non-obstructive urinary retention--an unusual presentation of prostate cancer.
AB  - Urinary retention due to obstruction is a common presenting symptom of carcinoma
      of the prostate. We report the first case in which non-obstructive urinary
      retention was the presenting symptom in a middle-aged patient with undiagnosed
      prostate cancer which had metastasized to the spine and caused cord compression.

PMID- 16303731
TI  - Male adnexal tumour of probable Wolffian duct origin.
AB  - Male adnexal tumours of Wolffian duct origin are very rare. They have variable
      malignant potential and surgical excision is recommended. We report the case of a
      56-year-old male who presented with a swelling in the perineum thought to be a
      haematoma as the result of a complication of a laparoscopic inguinal hernia
      repair. It recurred after incision and two attempts at drainage and was then
      completely excised. Histology revealed the lesion to be an adnexal tumour of
      probable Wolffian duct origin. To our knowledge there have only been two previous
      cases of male adnexal tumour of Wolffian duct origin reported in the literature.

PMID- 16303732
TI  - Genitourinary manifestations of Klippel-Trenaunay syndrome: report of two cases
      managed with systemic alpha-interferon.
AB  - We present our experience of two cases with genitourinary manifestations of
      Klippel-Trenaunay syndrome. A MEDLINE search for the period 2001-2004 was done
      using the keywords "Klippel-Trenaunay syndrome", "vascular malformation" and
      "genitourinary". Only three cases with genitourinary manifestations of this
      syndrome were reported during this period. Genitourinary problems are rare in
      Klippel-Trenaunay syndrome; however, their management may be a challenge for the
      urologist. In one of our patients who failed to respond to endoscopic laser
      coagulation and partial cystectomy we used systemic alpha-interferon, with a good
      short-term response.

PMID- 16303733
TI  - Xanthoma of the urinary bladder.
AB  - A 55-year-old male presented with asymptomatic macroscopic hematuria. A diagnosis
      of xanthoma of the urinary bladder was made histologically. Xanthoma of the
      urinary bladder is a rare condition. Its etiology, diagnosis and treatment are
      discussed.

PMID- 16303734
TI  - Privilege and confidentiality in 12-step self-help programs. Believing the
      promises could be hazardous to an addict's freedom.

PMID- 16303735
TI  - Whose brain is it anyway? The comparative law of post-mortem organ retention.

PMID- 16303736
TI  - Electronic medical records. Privacy, confidentiality, liability.

PMID- 16303737
TI  - Uterine fibroids and women's right to choose. Hysterectomies and informed
      consent.

PMID- 16303740
TI  - A bioinformatics analysis of protein tyrosine phosphatases in humans.
AB  - Protein tyrosine phosphatases (PTPs) cooperate with protein tyrosine kinases to
      regulate signal transduction pathways. Genome-wide surveys cataloging protein
      tyrosine phosphatases in humans have recently been carried out. Here, we present
      a bioinformatics analysis of protein tyrosine phosphatases in the human genome to
      examine their domain architecture, alternative splicing and pseudogenes. We
      present evidence that alternative transcripts exist for 25 out of 35 PTPs
      analyzed. These alternative transcripts include novel exons; skipped exons as
      well as cryptic donor/acceptor splice sites. We discovered a novel isoform of
      PTPN18 based on analysis of expressed sequence tags (ESTs). The deletion of 4
      exons in the catalytic domain of the novel isoform may alter the enzymatic
      activity toward its substrates. We were able to experimentally validate 2 of our
      novel isoform predictions through RT-PCR. Finally, a user-friendly web-based
      resource that consolidates the gene and protein annotations for all human protein
      tyrosine phosphatases has been developed and is freely available at
      http://ptpr.ibioinformatics.org.

PMID- 16303741
TI  - Codon and amino acid usage in two major human pathogens of genus Bartonella-
      optimization between replicational-transcriptional selection, translational
      control and cost minimization.
AB  - Intra-genomic variation in synonymous codon and amino acid usage in two human
      pathogens Bartonella henselae and B. quintana has been carried out through
      multivariate analysis. Asymmetric mutational bias, coupled with replicational
      transcriptional selection, has been identified as the prime selection force
      behind synonymous codon selection--a characteristic of the genus Bartonella, not
      exhibited by any other alpha-proteobacterial genome. Distinct codon usage
      patterns and low synonymous divergence values between orthologous sequences of
      highly expressed genes from the two Bartonella species indicate that there exists
      a residual intra-strand synonymous codon bias in the highly expressed genes,
      possibly operating at the level of translation. In the case of amino acid usage,
      the mean hydropathy level and aromaticity are the major sources of variation,
      both having nearly equal impact, while strand-specific mutational pressure and
      gene expressivity strongly influence the inter-strand variations. In both species
      under study, the highly expressed gene products tend not to contain heavy and/or
      aromatic residues, following the cost-minimization hypothesis in spite of their
      intracellular lifestyle. The codon and amino acid usage in these two human
      pathogens are, therefore, consequences of a complex balance between replicational
      transcriptional selection, translational control, protein hydropathy and cost
      minimization.

PMID- 16303742
TI  - High-throughput functional analysis of the Synechococcus elongatus PCC 7942
      genome.
AB  - Synechococcus elongatus PCC 7942 was the first cyanobacterial strain to be
      reliably transformed by exogenously added DNA and has become the model organism
      for cyanobacterial circadian rhythms. With a small genome (2.7 Mb) and well
      developed genetic tools, PCC 7942 provides an exceptional opportunity to
      elucidate the circadian mechanism through genetics. We describe a project to
      create mutations in every locus of the genome, both to assay each locus for its
      potential contribution to the circadian clock and to archive data for the
      cyanobacterial community. Cosmid clones that carry inserts of PCC 7942 DNA are
      saturated with transposon insertions in vitro to provide sequencing templates and
      substrates for mutagenesis of the PCC 7942 genome via homologous recombination.
      We have mutagenized 53% of the chromosome from 50 chromosome-bearing cosmids and
      identified the positions of insertions in 31 of those cosmids and the 46 kb
      plasmid, pANL. PCC 7942 mutants defective for 490 different genes have been
      screened for circadian phenotypes. Mutagenesis of three apparently essential
      loci, including clpPIIclpX, resulted in circadian phenotypes. We developed an
      effective antisense suppression method to further the analysis of essential
      genes. When completed, the set of comprehensive mutations will provide the
      community with a unique resource whose impact will extend beyond circadian
      research.

PMID- 16303743
TI  - Signal sequence and keyword trap in silico for selection of full-length human
      cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries.
AB  - We have developed an in silico method of selection of human full-length cDNAs
      encoding secretion or membrane proteins from oligo-capped cDNA libraries.
      Fullness rates were increased to about 80% by combination of the oligo-capping
      method and ATGpr, software for prediction of translation start point and the
      coding potential. Then, using 5'-end single-pass sequences, cDNAs having the
      signal sequence were selected by PSORT ('signal sequence trap'). We also applied
      'secretion or membrane protein-related keyword trap' based on the result of BLAST
      search against the SWISS-PROT database for the cDNAs which could not be selected
      by PSORT. Using the above procedures, 789 cDNAs were primarily selected and
      subjected to full-length sequencing, and 334 of these cDNAs were finally selected
      as novel. Most of the cDNAs (295 cDNAs: 88.3%) were predicted to encode secretion
      or membrane proteins. In particular, 165(80.5%) of the 205 cDNAs selected by
      PSORT were predicted to have signal sequences, while 70 (54.2%) of the 129 cDNAs
      selected by 'keyword trap' preserved the secretion or membrane protein-related
      keywords. Many important cDNAs were obtained, including transporters, receptors,
      and ligands, involved in significant cellular functions. Thus, an efficient
      method of selecting secretion or membrane protein-encoding cDNAs was developed by
      combining the above four procedures.

PMID- 16303744
TI  - Distinct gene expression profiles characterize cellular phenotypes of follicle
      associated epithelium and M cells.
AB  - Follicle-associated epithelium (FAE) covering Peyer's patches contains
      specialized epithelial M cells that take up ingested macromolecules and
      microorganisms from the lumen of the gut by transcytosis. Using high-density
      oligonucleotide microarrays, we analyzed the gene expression profiles of FAE and
      M cells in order to characterize their cellular phenotypes. The microarray data
      revealed that, among approximately 14,000 genes, 409 were expressed in FAE at
      twofold or higher levels compared to the intestinal epithelial cells (IECs) of
      the villi. These included genes involved in membrane traffic, host defense and
      transcriptional regulation, as well as uncharacterized genes. Real-time PCR and
      in situ hybridization analyses identified three molecules, ubiquitin D (Ub-D),
      tumor necrosis factor receptor superfamily 12a (TNFRsf12a), and transmembrane 4
      superfamily 4 (Tm4sf4), which were predominantly distributed throughout FAE, but
      were expressed little, if at all, in IECs. By contrast, transcripts of secretory
      granule neuroendocrine protein 1 (Sgne-1) were scattered in FAE, and were co
      localized with Ulex europaeus agglutinin-1 (UEA-1)-positive cells. This clearly
      suggests that expression of Sgne-1 in the gut is specific to M cells. Such a
      unique pattern of gene expression distinguishes FAE and M cells from IECs, and
      may reflect their cellular phenotype(s) associated with specific functional
      features.

PMID- 16303745
TI  - Frequency and distribution of AP-1 sites in the human genome.
AB  - The AP-1-binding sequences are promoter/enhancer elements that play an essential
      role in the induction of many genes in mammalian cells; however, the number of
      genes containing AP-1 sites remains unknown. In order to better address the
      overall effect of AP-1 on expression of genes encoded by the entire genome, a
      genome-wide analysis of the frequency and distribution of AP-1 sites would be
      useful; yet to date, no such analysis of AP-1 sites or any other
      promoter/enhancer elements has been performed. We present here our study of the
      consensus AP-1 site and two single-bp variants showing that the frequency of AP-1
      sites in promoter regions is significantly lower than their average rate of
      occurrence in the whole genomic sequence, as well as the frequency of a random
      heptanucleotide suggesting that nature has selected for a decrease in the
      frequency of AP-1 sites in the regulatory regions of genes. In addition, genes
      containing multiple AP-1 sites are more prevalent than those containing only one
      copy of an AP-1 site, which again may have evolved to allow for greater signal
      amplification or integration in the regulation of AP-1 target genes. However, the
      number of AP-1-regulated genes identified in various studies is far smaller than
      the number of genes containing potential AP-1 sites, indicating that not all AP-1
      sites are activated in a given cell under a given condition, and is consistent
      with the prediction by others that cellular context determines which AP-1 sites
      are targeted by AP-1.

PMID- 16303746
TI  - The complete plastid genome sequence of the haptophyte Emiliania huxleyi: a
      comparison to other plastid genomes.
AB  - The complete nucleotide sequence of the plastid genome of the haptophyte
      Emiliania huxleyi has been determined. E. huxleyi is the most abundant
      coccolithophorid and has a key role in the carbon cycle. It is also implicated in
      the production of dimethylsulphide (DMS), which is involved in cloud nucleation
      and may affect the global climate. Here, we report the plastid genome sequence of
      this ecologically and economically important species and compare its gene content
      and arrangement to other known plastid genomes. The genome is circular and
      consists of 105,309 bp with an inverted repeat of 4,841 bp. In terms of both
      genome size and gene content E. huxleyi cpDNA is substantially smaller than any
      other from the red plastid lineage. The genetic information is densely packed,
      with 86.8% of the genome specifying 110 identified protein-coding genes, 9 open
      reading frames, 28 different tRNAs, and 3 rRNAs. A detailed comparison to other
      plastid genomes, based on gene content, gene function, and gene cluster analysis
      is discussed. These analyses suggest a close relationship of the E. huxleyi cpDNA
      to the chlorophyll c-containing plastids from heterokonts and cryptophytes, and
      they support the origin of the chromophyte plastids from the red algal lineage.

PMID- 16303747
TI  - Complete genome sequence of the facultative anaerobic magnetotactic bacterium
      Magnetospirillum sp. strain AMB-1.
AB  - Magnetospirillum sp. strain AMB-1 is a Gram-negative alpha-proteobacterium that
      synthesizes nano-sized magnetites, referred to as magnetosomes, aligned
      intracellularly in a chain. The potential of this nano-sized material is growing
      and will be applicable to broad research areas. It has been expected that genome
      analysis would elucidate the mechanism of magnetosome formation by magnetic
      bacteria. Here we describe the genome of Magnetospirillum sp. AMB-1 wild type,
      which consists of a single circular chromosome of 4967148 bp. For identification
      of genes required for magnetosome formation, transposon mutagenesis and
      determination of magnetosome membrane proteins were performed. Analysis of a non
      magnetic transposon mutant library focused on three unknown genes from 2752
      unknown genes and three genes from 205 signal transduction genes. Partial
      proteome analysis of the magnetosome membrane revealed that the membrane contains
      numerous oxidation/reduction proteins and a signal response regulator that may
      function in magnetotaxis. Thus, oxidation/reduction proteins and elaborate
      multidomain signaling proteins were analyzed. This comprehensive genome analysis
      will enable resolution of the mechanisms of magnetosome formation and provide a
      template to determine how magnetic bacteria maintain a species-specific, nano
      sized, magnetic single domain and paramagnetic morphology.

PMID- 16303748
TI  - Genome-wide identification and molecular characterization of Ole_e_I, Allerg_1
      and Allerg_2 domain-containing pollen-allergen-like genes in Oryza sativa.
AB  - Pollen allergens play important roles in plant development in addition to their
      allergenic nature for human. More than 10 groups of pollen allergens have been
      reported. Among them, Pollen_Ole_e_I (Ole), Pollen_allerg_1 (Allerg1) and
      Pollen_allerg_2 (Allerg2) domain-containing proteins are the majority of
      allergens. We have identified 114 pollen-allergen-like genes in rice genome by
      bioinformatics using public databases. Among them, 45 genes encode Ole domain
      containing proteins, 62 with Allerg1 and 7 with Allerg2. They are distributed on
      11 of 12 rice chromosomes excluding chromosome 11. Comparison analysis of coding
      regions from both predicted genes and isolated full-length cDNAs showed that most
      of predicted genes were correct in the splicing of exons and introns, and only 7
      exhibited wrong predictions. The fact suggested the applicability of the
      prediction programs to identify pollen-allergen genes. Phylogenetic analysis
      revealed the high diversity within OsOle genes and recent evolutionary event in
      OsAllerg1 genes, and suggested that some of OsOle genes were new members of the
      family. Expression analysis by RT-PCR showed that most of the genes were
      expressed in all tested tissues and only eight genes exhibited panicle-specific
      expression, suggesting that pollen-allergen genes play roles in not only
      productive but also vegetative development.

PMID- 16303749
TI  - Influence of the 3'-UTR-length of mKIAA cDNAs and their sequence features to the
      mRNA expression level in the brain.
AB  - We have previously described the sequence features of approximately 1500 mouse
      KIAA (mKIAA) genes in comparison with those of human KIAA genes (Okazaki, N.,
      Kikuno, R., Inamoto, S., Hara, Y., Nagase, T., Ohara, O., and Koga, H. 2002, DNA
      Res., 9, 179-188; Okazaki, N., Kikuno, R., Ohara, R., Inamoto, S., Aizawa, H.,
      Yuasa, S., Nakajima, D., Nagase, T., Ohara, O., and Koga, H. 2003, DNA Res., 10,
      35-48; Okazaki, N., Kikuno, R., Ohara, R., Inamoto, S., Koseki, H., Hiraoka, S.,
      Saga, Y., Nagase, T., Ohara, O., and Koga, H. 2003, DNA Res., 10, 167-180; and
      Okazaki, N., F-Kikuno, R., Ohara, R., Inamoto, S., Koseki, H., Hiraoka, S., Saga,
      Y., Seino, S., Nishimura, M., Kaisho, T., Hoshino, K., Kitamura, H., Nagase, T.,
      Ohara, O., and Koga, H. 2004, DNA Res., 11, 205-218). To validate the orthologous
      relationship between mKIAA and KIAA genes in detail, we examined their
      chromosomal positions and evolutionary rate of synonymous substitutions and
      confirmed that >93% of the mKIAA/KIAA gene pairs are orthologous. During the
      sequence analysis of mKIAA genes, we found that 3'-untranslated region (3'-UTR)
      lengths of mKIAA and KIAA genes are extremely long. In the meanwhile, we have
      also examined the tissue-specific expression of approximately 1700 mKIAA genes
      using cDNA microarray and verified predominantly their expression in adult brain
      (Koga, H., Yuasa, S., Nagase, T., Shimada, K., Nagano, M., Imai, K., Ohara, R.,
      Nakajima, D., Murakami, M., Kawai, M., Miki, F., Magae, J., Inamoto, S., Okazaki,
      N., Ohara, O. 2004, DNA Res., 11, 293-304). To connect these two evidences, we
      statistically analysed the relationship between them by using the mKIAA genes.
      Consequently, a positive correlation was observed between the 3'-UTR lengths and
      the relative expression intensities in adult brain. Furthermore, we searched
      sequence elements in the 3'-UTR possibly related with their expression and found
      some candidates regarding the brain-specific expression.

PMID- 16303750
TI  - Genome-wide expression analysis reveals 100 adrenal gland-dependent circadian
      genes in the mouse liver.
AB  - Recent progress in genome-wide expression analysis has identified hundreds of
      circadian genes not only in the suprachiasmatic nucleus (the mammalian master
      clock) but also in peripheral tissues, such as heart, liver and kidney of
      mammals. Glucocorticoid is thought to be a circadian time cue for mammalian
      peripheral clocks. To identify the genes of which the circadian expression is
      regulated by endogenous glucocorticoids, we performed DNA microarray analysis
      using hepatic RNA from adrenalectomized (ADX) and sham-operated mice. We
      identified 169 genes that fluctuated between day and night in the livers of the
      sham-operated mice. Among these, 100 lost circadian rhythmicity in ADX mice.
      These included the genes for key enzymes of liver metabolic functions, such as
      glucokinase, HMG-CoA reductase and glucose-6-phosphatase. The circadian
      expression of Lpin1, FKBP51 and S-adenosyl methionine decarboxylase was also
      abolished in the ADX mice. On the other hand, although the circadian expression
      of clock or clock-related genes, such as mPer2, DBP, E4BP4, mDec1, Usp2 and Wee1
      remained almost totally intact in the liver of ADX mice, it was extremely damped
      in homozygous Clock mutant mice. The present findings suggested that one type of
      hepatic circadian genes in mice is transcriptionally regulated by core components
      of the circadian clock, such as CLOCK and BMAL1, and that the other depends on
      the adrenal gland.

PMID- 16303751
TI  - C21orf5, a new member of Dopey family involved in morphogenesis, could
      participate in neurological alterations and mental retardation in Down syndrome.
AB  - Availability of the human genome sequence promises important progress in the
      understanding of human pathologies, particularly for multifactorial diseases.
      Among these, Down syndrome (DS) is the most frequent genetic cause of mental
      retardation. A critical region of chromosome 21, the Down syndrome Chromosomal
      Region-1 (DCR-1), is responsible for many features of the DS phenotype including
      mental retardation. We studied DCR-1 C21orf5 as a new candidate gene for DS
      considering its restricted expression in key brain regions altered in DS patients
      and involved in learning and memory processes. To elucidate C21orf5 molecular
      function, we performed a comparative study of protein sequences in several
      species and showed that C21orf5 represents a new member of the Dopey leucine
      zipper-like family. The C21orf5 C-termini contains two highly conserved leucine
      like zipper domains in invertebrate and vertebrate species. Evolution analysis
      indicated a common ancestral origin of these protein sequences also suggesting a
      conserved function of this gene throughout phylogenesis. Mutations of the known
      C21orf5 homologous genes Aspergillus nidulans DopA, Saccharomyces cerevisiae Dop1
      and Caenorhabditis elegans pad1, determine morphological abnormalities. We
      studied transgenic mice carrying the human C21orf5 gene and we showed that this
      gene is overexpressed in brain regions by in situ hybridization and by real-time
      RT-PCR experiments. Interestingly, we also showed that these transgenic mice have
      an increased density of cortical cells overexpressing C21orf5. Similarly, DS
      patients have an altered lamination pattern in their cortex. Considering together
      our and previous findings, we suggest that the human dopey family member,
      C21orf5, could play a role in brain morphogenesis and, when overexpressed, it
      could participate in neurological features and mental retardation observed in DS
      patients.

PMID- 16303752
TI  - HTself: self-self based statistical test for low replication microarray studies.
AB  - Different statistical methods have been used to classify a gene as differentially
      expressed in microarray experiments. They usually require a number of
      experimental observations to be adequately applied. However, many microarray
      experiments are constrained to low replication designs for different reasons,
      from financial restrictions to scarcely available RNA samples. Although performed
      in a high-throughput framework, there are few experimental replicas for each gene
      to allow the use of traditional or state-of-art statistical methods. In this
      work, we present a web-based bioinformatics tool that deals with real-life
      problems concerning low replication experiments. It uses an empirically derived
      criterion to classify a gene as differentially expressed by combining two widely
      accepted ideas in microarray analysis: self-self experiments to derive intensity
      dependent cutoffs and non-parametric estimation techniques. To help laboratories
      without a bioinformatics infrastructure, we implemented the tool in a user
      friendly website (http://blasto.iq.usp.br/~rvencio/HTself).

PMID- 16303753
TI  - Complete nucleotide sequence of the chloroplast genome from the Tasmanian blue
      gum, Eucalyptus globulus (Myrtaceae).
AB  - The complete nucleotide sequence of the chloroplast genome of the hardwood
      species Eucalyptus globulus is presented and compared with chloroplast genomes of
      tree and non-tree angiosperms and two softwood tree species. The 160,286 bp
      genome is similar in gene order to that of Nicotiana, with an inverted repeat
      (IR) (26,393 bp) separated by a large single copy (LSC) region of 89,012 bp and a
      small single copy region of 18,488 bp. There are 128 genes (112 individual gene
      species and 16 genes duplicated in the inverted repeat) coding for 30 transfer
      RNAs, 4 ribosomal RNAs and 78 proteins. One pseudogene (psi-infA) and one pseudo
      ycf (psi-ycf15) were identified. The chloroplast genome of E. globulus is
      essentially co-linear with that of another hardwood tree species, Populus
      trichocarpa, except that the latter lacks rps16 and rpl32, and the IR has
      expanded in Populus to include rps19 (part of the LSC in E. globulus). Since the
      chloroplast genome of E. globulus is not significantly different from other tree
      and non-tree angiosperm taxa, a comparison of hardwood and softwood chloroplasts
      becomes, in essence, a comparison of angiosperm and gymnosperm chloroplasts. When
      compared with E. globulus, Pinus chloroplasts have a very small IR, two extra
      tRNAs and four additional photosynthetic genes, lack any functional ndh genes and
      have a significantly different genome arrangement. There does not appear to be
      any correlation between plant habit and chloroplast genome composition and
      arrangement.

PMID- 16303754
TI  - Cysteine-disulfide cross-linking to monitor SNARE complex assembly during
      endoplasmic reticulum-Golgi transport.
AB  - Assembly of cognate SNARE proteins into SNARE complexes is required for many
      intracellular membrane fusion reactions. However, the mechanisms that govern
      SNARE complex assembly and disassembly during fusion are not well understood. We
      have devised a new in vitro cross-linking assay to monitor SNARE complex assembly
      during fusion of endoplasmic reticulum (ER)-derived vesicles with Golgi-acceptor
      membranes. In Saccharomyces cerevisiae, anterograde ER-Golgi transport requires
      four SNARE proteins: Sec22p, Bos1p, Bet1p, and Sed5p. After tethering of ER
      derived vesicles to Golgi-acceptor membranes, SNARE proteins are thought to
      assemble into a four-helix coiled-coil bundle analogous to the structurally
      characterized neuronal and endosomal SNARE complexes. Molecular modeling was used
      to generate a structure of the four-helix ER-Golgi SNARE complex. Based on this
      structure, cysteine residues were introduced into adjacent SNARE proteins such
      that disulfide bonds would form if assembled into a SNARE complex. Our initial
      studies focused on disulfide bond formation between the SNARE motifs of Bet1p and
      Sec22p. Expression of SNARE cysteine derivatives in the same strain produced a
      cross-linked heterodimer of Bet1p and Sec22p under oxidizing conditions.
      Moreover, this Bet1p-Sec22p heterodimer formed during in vitro transport
      reactions when ER-derived vesicles containing the Bet1p derivative fused with
      Golgi membranes containing the Sec22p derivative. Using this disulfide cross
      linking assay, we show that inhibition of transport with anti-Sly1p antibodies
      blocked formation of the Bet1p-Sec22p heterodimer. In contrast, chelation of
      divalent cations did not inhibit formation of the Bet1p-Sec22p heterodimer during
      in vitro transport but potently inhibited Golgi-specific carbohydrate
      modification of glyco-pro-alpha factor. This data suggests that Ca(2+) is not
      directly required for membrane fusion between ER-derived vesicles and Golgi
      acceptor membranes.

PMID- 16303755
TI  - Growth phase-dependent activation of nitrogen-related genes by a control network
      of group 1 and group 2 sigma factors in a cyanobacterium.
AB  - It has been reported that an RNA polymerase sigma factor, SigC, mainly
      contributes to specific transcription from the promoter PglnB-54,-53 under
      nitrogen-deprived conditions during the stationary phase of cell growth in the
      cyanobacterium Synechocystis sp. strain PCC 6803 (Asayama, M., Imamura, S.,
      Yoshihara, S., Miyazaki, A., Yoshida, N., Sazuka, T., Kaneko, T., Ohara, O.,
      Tabata, S., Osanai, T., Tanaka, K., Takahashi, H., and Shirai, M. (2004) Biosci.
      Biotechnol. Biochem. 68, 477-487). In this study, we further examined the
      functions of group 2 sigma factors of RNA polymerase in NtcA-dependent nitrogen
      related gene expression in PCC 6803. Results indicated that SigB and SigC
      contribute to the transcription from PglnB-54,-53 with a sigma factor replaced in
      a growth phase-dependent manner. We also confirmed the contribution of SigB and
      SigC to the transcription of other NtcA-dependent genes, glnA, sigE, and amt1, as
      in the case of glnB. On the other hand, the transcription of glnN was dependent
      on SigB and SigE. In the SigB and SigC-based regulation, the level of SigB
      increased, but that of SigC was constant under conditions of nitrogen
      deprivation. Furthermore, it was found that SigC negatively and positively
      regulates the level of SigB in the log and stationary phase, respectively. SigC
      also had a positive effect on the level of sigB transcript during the stationary
      phase. In contrast, SigB acts positively on SigC levels in both growth phases.
      These results and previous findings indicated that multiple group 2 sigma factors
      take part in the control of NtcA-dependent nitrogen-related gene expression in
      cooperation with a group 1 sigma factor, SigA.

PMID- 16303756
TI  - Heparan sulfate polymerization in Drosophila.
AB  - The formation of heparan sulfate (HS) chains is catalyzed by glycosyltransferases
      encoded by EXT (hereditary multiple exostosin gene) family members. Genetic
      screening for mutations affecting morphogen signaling pathways in Drosophila has
      identified three genes, tout-velu (ttv), sister of tout-velu (sotv), and brother
      of toutvelu (botv), which encode homologues of human EXT1, EXT2, and EXTL3,
      respectively. So far, in vitro glycosyltransferase activities have been
      demonstrated only for BOTV/DEXTL3, which harbors both N
      acetylglucosaminyltransferase-I (GlcNAcT-I) and N-acetylglucosaminyltransferase
      II (GlcNAcT-II) activities responsible for the chain initiation and elongation of
      HS, and no glucuronyltransferase-II (GlcAT-II) activity. Here we demonstrated
      that TTV/DEXT1 and SOTV/DEXT2 had GlcNAcT-II and GlcAT-II activities required for
      the biosynthesis of repeating disaccharide units of the HS backbone, and the
      coexpression of TTV with SOTV markedly augmented both glycosyltransferase
      activities when compared with the expression of TTV or SOTV alone. Moreover, the
      polymerization of HS was demonstrated on a linkage region analogue as an acceptor
      substrate by BOTV and an enzyme complex composed of TTV and SOTV (TTV-SOTV). In
      contrast to human, TTV-SOTV exhibited no GlcNAcT-I activity, indicating that
      BOTV/DEXT3, which is an EXT-Like gene and possesses GlcNAcT-I activity required
      for the initiation of HS, is indispensable for the biosynthesis of HS chains in
      Drosophila. Thus, all three EXT members in Drosophila, TTV, SOTV, and BOTV, are
      required for the biosynthesis of full-length HS in Drosophila.

PMID- 16303757
TI  - A novel role of sodium butyrate in the regulation of cancer-associated aromatase
      promoters I.3 and II by disrupting a transcriptional complex in breast adipose
      fibroblasts.
AB  - The aromatase gene encodes the key enzyme for estrogen formation. Aromatase
      enzyme inhibitors eliminate total body estrogen production and are highly
      effective therapeutics for postmenopausal breast cancer. A distal promoter (I.4)
      regulates low levels of aromatase expression in tumor-free breast adipose tissue.
      Two proximal promoters (I.3/II) strikingly induce in vivo aromatase expression in
      breast fibroblasts surrounding malignant cells. Treatment of breast fibroblasts
      with medium conditioned with malignant breast epithelial cells (MCM) or a
      surrogate hormonal mixture (dibutyryl (Bt2)cAMP plus phorbol diacetate (PDA))
      induces promoters I.3/II. The mechanism of promoter-selective expression,
      however, is not clear. Here we reported that sodium butyrate profoundly decreased
      MCM- or Bt2cAMP + PDA-induced promoter I.3/II-specific aromatase mRNA. MCM,
      Bt2cAMP + PDA, or sodium butyrate regulated aromatase mRNA or activity only via
      promoters I.3/II but not promoters I.1 or I.4 in breast, ovarian, placental, and
      hepatic cells. Mechanistically, recruitment of phosphorylated ATF-2 by a CRE (
      211/-199, promoter I.3/II) conferred inductions by MCM or Bt2cAMP + PDA.
      Chromatin immunoprecipitation-PCR and immunoprecipitation-immunoblotting assays
      indicated that MCM or Bt2cAMP + PDA stabilized a complex composed of
      phosphorylated ATF-2, C/EBPbeta, and cAMP-response element-binding protein (CREB)
      binding protein in the common regulatory region of promoters I.3/II. Overall,
      histone acetylation patterns of promoters I.3/II did not correlate with sodium
      butyrate-dependent silencing of promoters I.3/II. Sodium butyrate, however,
      consistently disrupted the activating complex composed of phosphorylated ATF-2,
      C/EBPbeta, and CREB-binding protein. This was mediated, in part, by decreased ATF
      2 phosphorylation. Together, these findings represent a novel mechanism of sodium
      butyrate action and provide evidence that aromatase activity can be ablated in a
      signaling pathway- and cell-specific fashion.

PMID- 16303758
TI  - Proline oxidase, a proapoptotic gene, is induced by troglitazone: evidence for
      both peroxisome proliferator-activated receptor gamma-dependent and -independent
      mechanisms.
AB  - Proline oxidase (POX) is a redox enzyme localized in the mitochondrial inner
      membrane. We and others have shown that POX is a p53-induced gene that can
      mediate apoptosis through generation of reactive oxygen species (ROS). The
      peroxisome proliferator-activated receptor gamma (PPARgamma) ligand troglitazone
      was found to activate the POX promoter in colon cancer cells. PPARgamma ligands
      have been reported to induce apoptosis in a variety of cancer cells. In HCT116
      cells expressing a wild-type PPARgamma, troglitazone enhanced the binding of
      PPARgamma to PPAR-responsive element in the POX promoter and increased endogenous
      POX expression. Blocking of PPARgamma activation either by antagonist GW9662 or
      deletion of PPAR-responsive element in the POX promoter only partially decreased
      the POX promoter activation in response to troglitazone, indicating also the
      involvement of PPARgamma-independent mechanisms. Further, troglitazone also
      induced p53 protein expression in HCT116 cells, which may be the possible
      mechanism for PPARgamma-independent POX activation, since POX has been shown to
      be a downstream mediator in p53-induced apoptosis. In HCT15 cells, with both
      mutant p53 and mutant PPARgamma, there was no effect of troglitazone on POX
      activation, whereas in HT29 cells, with a mutant p53 and wild type PPARgamma,
      increased activation was observed by ligand stimulation, indicating that both
      PPARgamma-dependent and -independent mechanisms are involved in the troglitazone
      induced POX expression. A time- and dose-dependent increase in POX catalytic
      activity was obtained in HCT116 cells treated with troglitazone with a
      concomitant increase in the production of intracellular ROS. Our results suggest
      that the induction of apoptosis by troglitazone may, at least in part, be
      mediated by targeting POX gene expression for generation of ROS by POX both by
      PPARgamma-dependent and -independent mechanisms.

PMID- 16303759
TI  - Localization of the lipopolysaccharide-binding protein in phospholipid membranes
      by atomic force microscopy.
AB  - Lipopolysaccharides (LPS; endotoxin) activate immunocompetent cells of the host
      via a transmembrane signaling process. In this study, we investigated the
      function of the LPS-binding protein (LBP) in this process. The cytoplasmic
      membrane of the cells was mimicked by lipid liposomes adsorbed on mica, and the
      lateral organization of LBP in these membranes and its interaction with LPS
      aggregates were characterized by atomic force microscopy. Using cantilever tips
      functionalized with anti-LBP antibodies, single LBP molecules were localized in
      the membrane at low concentrations. At higher concentrations, LBP formed clusters
      of several molecules and caused cross-linking of lipid bilayers. The addition of
      LPS to LBP-containing liposomes led to the formation of LPS domains in the
      membranes, which could be inhibited by anti-LBP antibodies. Thus, LBP mediates
      the fusion of lipid membranes and LPS aggregates.

PMID- 16303760
TI  - HSF1 down-regulates XAF1 through transcriptional regulation.
AB  - Studies have indicated the role of HSF1 (heat-shock transcription factor 1) in
      repressing the transcription of some nonheat shock genes. XAF1 (XIAP-associated
      factor 1) was an inhibitor of apoptosis-interacting protein with the effect of
      antagonizing the cytoprotective role of XIAP. XAF1 expression was lower in
      gastrointestinal cancers than in normal tissues with the mechanism unclear. Here
      we showed that gastrointestinal cancer tissues expressed higher levels of HSF1
      than matched normal tissues. The expression of XAF1 and HSF1 was negatively
      correlated in gastrointestinal cancer cell lines. Stress stimuli, including heat,
      hypo-osmolarity, and H2O2, significantly suppressed the expression of XAF1,
      whereas the alteration of HSF1 expression negatively correlated with XAF1
      expression. We cloned varying lengths of the 5'-flanking region of the XAF1 gene
      into luciferase reporter vectors, and we evaluated their promoter activities. A
      transcription silencer was found between the -592- and -1414-nucleotide region
      that was rich in nGAAn/nT-TCn elements (where n indicates G, A, T, or C). A high
      affinity and functional HSF1-binding element within the -862/-821-nucleotide
      region was determined by electrophoretic mobility shift assay and chromatin
      immunoprecipitation assay. Inactivation of this "heat-shock element" by either
      site-directed mutation or an HSF1 inhibitor, pifithrin-alpha, restored the
      promoter activity of the silencer structure. Moreover, pretreatment with
      antioxidants suppressed HSF1 binding activity and increased the transcriptional
      activity and expression of XAF1. These findings suggested that endogenous stress
      pressure in cancer cells sustained the high level expression of HSF1 and
      subsequently suppressed XAF1 expression, implicating the synergized effect of two
      anti-apoptotic protein families, HSP and inhibitors of apoptosis, in
      cytoprotection under stress circumstances.

PMID- 16303762
TI  - Astrocyte-specific expression of the alpha1-antichymotrypsin and glial fibrillary
      acidic protein genes requires activator protein-1.
AB  - An amyloid-associated serine proteinase inhibitor (serpin), alpha(1)
      antichymotrypsin (ACT), is encoded by a gene located within the distal serpin
      subcluster on human chromosome 14q32.1. The expression of these distal serpin
      genes is determined by tissue-specific chromatin structures that allow their
      ubiquitous expression in hepatocytes; however, their expression is limited to a
      single ACT gene in astrocytes. In astrocytes and glioma cells, six specific DNase
      I-hypersensitive sites (DHSs) were found located exclusively in the 5'-flanking
      region of the ACT gene. We identified two enhancers that mapped to the two DHSs
      at -13 kb and -11.5 kb which contain activator protein-1 (AP-1) binding sites,
      both of which are critical for basal astrocyte-specific expression of ACT
      reporters. In vivo, these elements are occupied by c-jun homodimers in
      unstimulated cells and c-jun/c-fos heterodimers in interleukin-1-treated cells.
      Moreover, functional c-jun is required for the expression of ACT in glioma cells
      because both transient and stable inducible overexpression of dominant-negative c
      jun(TAM67) specifically abrogates basal and reduces cytokine-induced expression
      of ACT. Expression-associated methylation of lysine 4 of histone H3 was also lost
      in these cells, but the DHS distribution pattern and global histone acetylation
      were not changed upstream of the ACT locus. Interestingly, functional AP-1 is
      also indispensable for the expression of glial fibrillary acidic protein (GFAP),
      which is an astrocyte-specific marker. We propose that AP-1 is a key
      transcription factor that, in part, controls astrocyte-specific expression of
      genes including the ACT and GFAP genes.

PMID- 16303761
TI  - Mast cell and neutrophil peptidases attack an inactivation segment in hepatocyte
      growth factor to generate NK4-like antagonists.
AB  - Hepatocyte growth factor (HGF) is a plasminogen-like protein with an alpha chain
      linked to a trypsin-like beta chain without peptidase activity. The interaction
      of HGF with c-met, a receptor tyrosine kinase expressed by many cells, is
      important in cell growth, migration, and formation of endothelial and epithelial
      tubes. Stimulation of c-met requires two-chain, disulfide-linked HGF. Portions of
      an alpha chain containing an N-terminal segment and four kringle domains (NK4)
      antagonize HGF activity. Until now, no physiological pathway for generating NK4
      was known. Here we show that chymases, which are chymotryptic peptidases secreted
      by mast cells, hydrolyze HGF, thereby abolishing scatter factor activity while
      generating an NK4-like antagonist of HGF scatter factor activity. Thus, chymase
      interferes with HGF directly by destroying active protein and indirectly by
      generating an antagonist. The site of hydrolysis, Leu480, lies in the alpha chain
      on the N-terminal side of the cysteine linking the alpha and beta chains. This
      site appears to be specific for HGF because chymase does not hydrolyze other
      plasminogen-like proteins, such as macrophage-stimulating protein and plasminogen
      itself. Mast cell/neutrophil cathepsin G and neutrophil elastase generate similar
      fragments of HGF by cleaving near the chymase site. Mast cell and neutrophil
      peptidases are secreted during tissue injury, infection, ischemia, and allergic
      inflammation, where they may oppose HGF effects on epithelial repair. Thus, HGF
      possesses an "inactivation segment" that serves as an Achilles' heel attacked by
      inflammatory proteases. This work reveals a potential physiological pathway for
      inactivation of HGF and generation of NK4-like antagonists.

PMID- 16303763
TI  - Aberrant folding of a mutant Stat5b causes growth hormone insensitivity and
      proteasomal dysfunction.
AB  - A predicted alanine to proline substitution in Stat5b that results in profound
      short stature, growth hormone insensitivity, and immunodeficiency represents the
      first natural mutation of this transcription factor in a human. To understand the
      mechanisms responsible for these pathophysiological abnormalities, we have
      studied the biochemical and biophysical properties of the mutant Stat5b molecule.
      In a cellular reconstitution model growth hormone robustly stimulated tyrosine
      phosphorylation and transcriptional activity of wild-type Stat5b while
      Stat5bA630P was minimally modified and did not promote reporter gene expression.
      Steady state levels of Stat5bWT were approximately 3-fold higher than Stat5bA630P
      in cell extracts prepared with nonionic detergents. Although initial rates of
      biosynthesis of both proteins were similar, pulse-chase experiments established
      that the apparent half-life of newly synthesized soluble Stat5bA630P was <15% of
      Stat5bWT (3.5 h versus >24 h). Stat5bA630P accumulated in cells primarily in
      cytoplasmic inclusion bodies. Structural analysis of the isolated SH2 domain
      containing the A630P mutation showed that it resembled the wild-type SH2 segment
      but that it exhibited reduced thermodynamic stability and slower folding
      kinetics, displayed an increased hydrophobic surface, and was prone to
      aggregation in solution. Our results are compatible with a model in which
      Stat5bA630P is an inactive transcription factor by virtue of its aberrant folding
      and diminished solubility triggered by a misfolded SH2 domain. The potential for
      aggregation and formation of cytoplasmic inclusions raises the possibility that
      Stat5bA630P could produce additional defects through inhibition of proteasome
      function.

PMID- 16303764
TI  - The CLN9 protein, a regulator of dihydroceramide synthase.
AB  - A new variant of a group of pediatric neurodegenerative diseases known as
      neuronal ceroid lipofuscinosis (NCL) or Batten disease has been identified. It is
      termed CLN9-deficient. CLN9-deficient fibroblasts have a distinctive phenotype of
      rapid growth and increased apoptosis and diminished levels of ceramide,
      dihydroceramide, and sphingomyelin. Transfection with CLN8 but not other NCL
      genes corrected growth and apoptosis in CLN9-deficient cells, although the entire
      CLN8 sequence was normal. CLN8 is one of the TRAM-Lag1-CLN8 proteins containing a
      Lag1 motif. The latter imparts (dihydro)ceramide synthase activity to yeast
      cells. Transfection with the yeast gene Lag1 Sc and the human homolog LASS1
      increased ceramide levels and partially corrected growth and apoptosis in CLN9
      deficient cells. LASS2,-4,,-5, and -6 also corrected growth and apoptosis.
      Dihydroceramide levels and dihydroceramide synthase activity were markedly
      diminished in CLN9-deficient cells. Sequencing of LASS1, LASS2, LASS4, LASS5, and
      LASS6 genes was normal, and expression levels were increased or normal in CLN9
      deficient cells by reverse transcription-PCR. N-(4-Hydroxyphenyl)retinamide (4
      HPR), a dihydroceramide synthase activator, corrected growth and apoptosis and
      increased dihydroceramide synthase activity. Ceramide levels dropped further, and
      there was no increase in de novo ceramide synthesis, probably due to the effects
      of 4-HPR as activator of dihydroceramide synthase and inhibitor of
      dihydroceramide desaturase. Fumonisin B1, a dihydroceramide synthase inhibitor,
      exaggerated the CLN9-deficient phenotype of accelerated growth, decreased
      ceramide and increased apoptosis. This was neutralized by 4-HPR. We conclude that
      the CLN9 protein may be a regulator of dihydroceramide synthase and that 4-HPR
      could be developed as a treatment for CLN9-deficient patients.

PMID- 16303765
TI  - Protein kinase A-mediated phosphorylation modulates cytochrome c oxidase function
      and augments hypoxia and myocardial ischemia-related injury.
AB  - We have investigated the effects of hypoxia and myocardial ischemia/reperfusion
      on the structure and function of cytochrome c oxidase (CcO). Hypoxia (0.1% O(2)
      for 10 h) and cAMP-mediated inhibition of CcO activity were accompanied by
      hyperphosphorylation of subunits I, IVi1, and Vb and markedly increased reactive
      O(2) species production by the enzyme complex in an in vitro system that uses
      reduced cytochrome c as an electron donor. Both subunit phosphorylation and
      enzyme activity were effectively reversed by 50 nm H89 or 50 nm myristoylated
      peptide inhibitor (MPI), specific inhibitors of protein kinase A, but not by
      inhibitors of protein kinase C. In rabbit hearts subjected to global and focal
      ischemia, CcO activity was inhibited in a time-dependent manner and was
      accompanied by hyperphosphorylation as in hypoxia. Additionally, CcO activity and
      subunit phosphorylation in the ischemic heart were nearly completely reversed by
      H89 or MPI added to the perfusion medium. Hyperphosphorylation of subunits I,
      IVi1, and Vb was accompanied by reduced subunit contents of the
      immunoprecipitated CcO complex. Most interestingly, both H89 and MPI added to the
      perfusion medium dramatically reduced the ischemia/reperfusion injury to the
      myocardial tissue. Our results pointed to an exciting possibility of using CcO
      activity modulators for controlling myocardial injury associated with ischemia
      and oxidative stress conditions.

PMID- 16303766
TI  - Relaxin stimulates leukocyte adhesion and migration through a relaxin receptor
      LGR7-dependent mechanism.
AB  - Leukocytes are critical effectors of inflammation and tumor biology. Chemokine
      like factors produced by such inflammatory sites are key mediators of tumor
      growth that activate leukocytic recruitment and tumor infiltration and suppress
      immune surveillance. Here we report that the endocrine peptide hormone, relaxin,
      is a regulator of leukocyte biology with properties important in recruitment to
      sites of inflammation. This study uses the human monocytic cell line THP-1 and
      normal human peripheral blood mononuclear cells to define a novel role for
      relaxin in regulation of leukocyte adhesion and migration. Our studies indicate
      that relaxin promotes adenylate cyclase activation, substrate adhesion, and
      migratory capacity of mononuclear leukocytes through a relaxin receptor LGR7
      dependent mechanism. Relaxin-stimulated cAMP accumulation was observed to occur
      primarily in non-adherent cells. Relaxin stimulation results in increased
      substrate adhesion and increased migratory activity of leukocytes. In addition,
      relaxin-stimulated substrate adhesion resulted in enhanced chemotaxis to monocyte
      chemoattractant protein-1. These responses in THP-1 and peripheral blood
      mononuclear cells are relaxin dose-dependent and proportional to cAMP
      accumulation. We further demonstrate that LGR7 is critical for mediating these
      biological responses by use of RNA interference lentiviral short hairpin
      constructs. In summary, we provide evidence that relaxin is a novel leukocyte
      stimulatory agent with properties affecting adhesion and chemomigration.

PMID- 16303767
TI  - Phosphatidylserine in addition to phosphatidylethanolamine is an in vitro target
      of the mammalian Atg8 modifiers, LC3, GABARAP, and GATE-16.
AB  - In yeast, phosphatidylethanolamine is a target of the Atg8 modifier in
      ubiquitylation-like reactions essential for autophagy. Three human Atg8 (hAtg8)
      homologs, LC3, GABARAP, and GATE-16, have been characterized as modifiers in
      reactions mediated by hAtg7 (an E1-like enzyme) and hAtg3 (an E2-like enzyme) as
      in yeast Atg8 lipidation, but their final targets have not been identified. The
      results of a recent study in which COS7 cells were incubated with
      [14C]ethanolamine for 48 h suggested that phosphatidylethanolamine is a target of
      LC3. However, these results were not conclusive because of the long incubation
      time. To identify the phospholipid targets of Atg8 homologs, we reconstituted
      conjugation systems for mammalian Atg8 homologs in vitro using purified
      recombinant Atg proteins and liposomes. Each purified mutant Atg8 homolog with an
      exposed C-terminal Gly formed an E1-substrate intermediate with hAtg7 via a
      thioester bond in an ATP-dependent manner and formed an E2-substrate intermediate
      with hAtg3 via a thioester bond dependent on ATP and hAtg7. A conjugated form of
      each Atg8 homolog was observed in the presence of hAtg7, hAtg3, ATP, and
      liposomes. In addition to phosphatidylethanolamine, in vitro conjugation
      experiments using synthetic phospholipid liposomes showed that phosphatidylserine
      is also a target of LC3, GABARAP, and GATE-16. In contrast, thin layer
      chromatography of phospholipids released on hAtg4B-digestion from endogenous LC3
      phospholipid conjugate revealed that phosphatidylethanolamine, but not
      phosphatidylserine, is the predominant target phospholipid of LC3 in vivo. The
      discrepancy between in vitro and in vivo reactions suggested that there may be
      selective factor(s) involved in the endogenous LC3 conjugation system.

PMID- 16303768
TI  - Down-regulation of endogenous amyloid precursor protein processing due to
      cellular aging.
AB  - Processing of amyloid precursor protein (APP) is a well acknowledged central
      pathogenic mechanism in Alzheimer disease. However, influences of age-associated
      cellular alterations on the biochemistry of APP processing have not been studied
      in molecular detail so far. Here, we report that processing of endogenous APP is
      down-regulated during the aging of normal human fibroblasts (IMR-90). The
      generation of intracellular APP cleavage products C99, C83, and AICD gradually
      declines with increasing life span and is accompanied by a reduced secretion of
      soluble APP (sAPP) and sAPPalpha. Further, the maturation of APP was reduced in
      senescent cells, which has been shown to be directly mediated by age-associated
      increased cellular cholesterol levels. Of the APP processing secretases, protein
      levels of constituents of the gamma-secretase complex, presenilin-1 (PS1) and
      nicastrin, were progressively reduced during aging, resulting in a progressive
      decrease in gamma-secretase enzymatic activity. ADAM10 (a disintegrin and
      metalloprotease 10) and BACE (beta-site APP-cleaving enzyme) protein levels
      exhibited no age-associated regulation, but interestingly, BACE enzymatic
      activity was increased in aged cells. PS1 and BACE are located in detergent
      resistant membranes (DRMs), well structured membrane microdomains exhibiting high
      levels of cholesterol, and caveolin-1. Although total levels of both structural
      components of DRMs were up-regulated in aged cells, their particular DRM
      association was decreased. This age-dependent membrane modification was
      associated with an altered distribution of PS1 and BACE between DRM and non-DRM
      fractions, very likely affecting their APP processing potential. In conclusion,
      we have found a significant modulation of endogenous APP processing and
      maturation in human fibroblasts caused by age-associated alterations in cellular
      biochemistry.

PMID- 16303769
TI  - Pneumococcal beta-lactam resistance due to a conformational change in penicillin
      binding protein 2x.
AB  - Streptococcus pneumoniae is a life-threatening human pathogen that is
      increasingly resistant to a wide array of drugs. Resistance to beta-lactams, the
      most widely used antibiotics, is correlated with tens of amino acid substitutions
      in their targets; that is, the penicillin-binding proteins (PBPs), resulting from
      multiple events of recombination. To discriminate relevant substitutions from
      those that are incidental to the recombination process, we report the exhaustive
      characterization of all the mutations in the transpeptidase domain of PBP2x from
      the highly resistant strain 5204. A semi-automated method combining biochemical
      and microbiological approaches singled out 6 mutations of 41 (15%) that are
      essential for high level resistance. The hitherto uncharacterized I371T, R384G,
      M400T, and N605T together with the previously studied T338M and M339F account for
      nearly all the loss of affinity of PBP2x for beta-lactams. Most interestingly,
      I371T and R384G cause the conformational change of a loop that borders the
      entrance of the active site cavity, hampering antibiotic binding. For the first
      time all the mutations of a PBP relevant to beta-lactam resistance have been
      identified, providing new mechanistic insights. Most notable is the relationship
      between the decreased susceptibility to beta-lactams and the dynamic behavior of
      a loop.

PMID- 16303770
TI  - A novel functional interaction between the Sp1-like protein KLF13 and SREBP-Sp1
      activation complex underlies regulation of low density lipoprotein receptor
      promoter function.
AB  - Cholesterol homeostasis is regulated by a family of transcription factors
      designated sterol regulatory element-binding proteins (SREBPs). Precise control
      of SREBP-targeted genes requires additional interactions with co-regulatory
      transcription factors. In the case of the low density lipoprotein receptor
      (LDLR), SREBP cooperates with the specificity protein Sp1 to activate the
      promoter. In this report, we describe a novel pathway in LDLR transcriptional
      regulation distinct from the SREBP-Sp1 activation complex involving the Sp1-like
      protein Krueppel-like factor 13 (KLF13). Using a combination of RNA interference,
      electrophoretic mobility shift, chromatin immunoprecipitation, and reporter
      assays, deletion, and site-directed mutagenesis, we demonstrated that KLF13
      mediates repression in a DNA context-selective manner. KLF13 repression of LDLR
      promoter activity appears to be needed to keep the receptor silent, a state that
      can be antagonized by Sp1, SREBP, and inhibitors of histone deacetylase activity.
      Chromatin immunoprecipitation assay confirmed that KLF13 binds proximal LDLR DNA
      sequences in vivo and that exogenous oxysterol up-regulates such binding.
      Together these studies identify a novel regulatory pathway in which gene
      repression by KLF13 must be overcome by the Sp1-SREBP complex to activate the
      LDLR promoter. Therefore, these data should replace a pre-existent and more
      simple paradigm that takes into consideration only the induction of the activator
      proteins Sp1-SREBP as necessary for LDLR promoter drive without including default
      repression, such as that by KLF13, of the LDLR gene.

PMID- 16303771
TI  - Tissue-type plasminogen activator acts as a cytokine that triggers intracellular
      signal transduction and induces matrix metalloproteinase-9 gene expression.
AB  - Tissue-type plasminogen activator (tPA), a serine protease well known for
      generating plasmin, has been demonstrated to induce matrix metalloproteinase-9
      (MMP-9) gene expression and protein secretion in renal interstitial fibroblasts.
      However, exactly how tPA transduces its signal into the nucleus to control gene
      expression is unknown. This study investigated the mechanism by which tPA induces
      MMP-9 gene expression. Both wild-type and non-enzymatic mutant tPA were found to
      induce MMP-9 expression in rat kidney interstitial fibroblasts (NRK-49F),
      indicating that the actions of tPA are independent of its proteolytic activity.
      tPA bound to the low density lipoprotein receptor-related protein-1 (LRP-1) in
      NRK-49F cells, and this binding was competitively abrogated by the LRP-1
      antagonist, the receptor-associated protein. In mouse embryonic fibroblasts (PEA
      13) lacking LRP-1, tPA failed to induce MMP-9 expression. Furthermore, tPA
      induced rapid tyrosine phosphorylation on the beta subunit of LRP-1, which was
      followed by the activation of Mek1 and its downstream Erk-1 and -2. Blockade of
      Erk-1/2 activation by the Mek1 inhibitor abolished MMP-9 induction by tPA in NRK
      49F cells. Conversely, overexpression of constitutively activated Mek1 induced
      Erk-1/2 phosphorylation and MMP-9 expression. In mouse obstructed kidney, tPA,
      LRP-1, and MMP-9 were concomitantly induced in the renal interstitium.
      Collectively, these results suggest that besides its classical proteolytic
      activity, tPA acts as a cytokine that binds to the cell membrane receptor LRP-1,
      induces its tyrosine phosphorylation, and triggers intracellular signal
      transduction, thereby inducing specific gene expression in renal interstitial
      fibroblasts.

PMID- 16303772
TI  - Physical restriction of pods causes seed size reduction of a brassinosteroid
      deficient faba bean (Vicia faba).
AB  - BACKGROUND AND AIMS: A brassinosteroid-deficient mutant faba bean (Vicia faba
      'Rinrei') shows dwarfism in many organs including pods and seeds. 'Rinrei' has
      normal-sized seeds together with dwarf seeds, suggesting that dwarfism in the
      seed may be indirectly caused by brassinosteroid deficiency. The mechanism of
      seed size reduction in this mutant was investigated. METHODS: The associations
      between seed orientation in the pod, seed numbers per pod and pod lengths with
      seed sizes were analysed in 'Rinrei' and the wild-type plant. KEY RESULTS:
      'Rinrei' seeds are tightly arranged in pods containing two or three seeds. Seed
      size decreased as the number of seeds per pod increased or as the length of the
      pod decreased. Where no physical restriction occurred between seeds in a pod, the
      wild-type faba bean seeds had a nearly constant size regardless of seed number
      per pod or pod length. 'Rinrei' seeds in pods containing single seeds were the
      same size as wild-type seeds. Brassinolide treatment increased the seed size and
      the length of pods containing three seeds in 'Rinrei'. CONCLUSION: Seed size of
      'Rinrei' is mainly regulated through a reduction of pod length due to
      brassinosteroid deficiency; physical restriction within pods causes a reduction
      in seed size. These results suggest a possible mechanism for increasing faba bean
      yields to optimal levels.

PMID- 16303773
TI  - The treatment of common mental health problems in general practice.
AB  - BACKGROUND: Previous studies report GPs under-treat mental health disorders,
      particularly depression, and treatments are non-specific and lack an evidence
      base. They conclude further training and education of GP's is required.
      OBJECTIVE: To describe the treatment of common mental health disorders in
      relation to the level and severity of psychological problems as defined by the GP
      and external assessment. METHODS: Cross sectional survey of General Practice
      attenders in New Zealand. Fifty consecutive adult patients were recruited from
      each practice of 70 randomly selected GP's. The psychological status of 773
      respondents selected via the General Health Questionnaire (GHQ) was assessed, and
      details of management provided. Management options were compared with the level
      of psychological problem identified by the GP. RESULTS: Treatment varied
      depending on the level of problem identification, and frequency of consultation,
      from 93% given treatment when an explicit diagnosis was made to 22.3% in patients
      with subclinical symptoms. The most commonly given treatment with an explicit
      diagnosis was psychotropic medication [73% (95% CI 63.6-82.9)] while for those
      patients with subclinical symptoms the most common form of treatment was
      discussion and counselling [15.7% (7.1-24.2)]. Only 1.7% (0.3-3.0) of patients
      with subclinical symptoms received psychotropics. CONCLUSION: There is a clear
      association between the level of psychological problem identified and treatment.
      In contrast to previous views that treatment often appears to be given regardless
      of diagnosis, these results provide a picture of general practice management of
      common mental disorders more in line with evidence-based practice than previously
      described.

PMID- 16303774
TI  - Onset and persistence of depression in older people--results from a 2-year
      community follow-up study.
AB  - BACKGROUND: baseline physical health, disability and social support have been
      shown to predict depression onset, but findings for persistence are inconsistent.
      For onset and persistence of depression, the effect of changes in these risk
      factors over time is unclear. OBJECTIVE: to use baseline factors and change in
      factors over time to predict onset and persistence of depression over a 2-year
      period. METHODS: a prospective cohort study with index assessment and 2-year
      follow-up of patients initially aged > or =65 years registered with two South
      London practices (n = 1,164). Depression was defined by a score >5/15 on the 15
      item Geriatric Depression Scale. Associations between risk factors and onset and
      persistence of depression were analysed using multiple logistic regression.
      RESULTS: the incidence of depression was 8.4%, while depression persisted amongst
      61.2% of those depressed at baseline. Comparing onset and persistence suggested
      some common predictors: greater baseline depression score; and follow-up measures
      of poor general health and compromised social support. There was some evidence
      that pain and worsening disability were more important for depression onset. In
      contrast, low baseline belief in powerful others (health locus of control
      measure) predicted persistence only. CONCLUSION: focusing on older people with
      increasing disability, pain, physical ill-health and compromised social support
      should help in both the prevention and recognition of onset of later-life
      depression. In older people with depression, those with the highest symptom
      scores and low belief in powerful others at baseline were more likely to develop
      chronic symptoms and could be targeted for more intensive treatment and support.

PMID- 16303775
TI  - Reversal of diabetic peripheral neuropathy with phototherapy (MIRE) decreases
      falls and the fear of falling and improves activities of daily living in seniors.
AB  - OBJECTIVE: to determine whether restoration of sensation, impaired due to
      diabetic peripheral neuropathy (DPN), would reduce the number of falls and the
      fear of falling and improve activities of daily living (ADL) in a Medicare-aged
      population. DESIGN: retrospective cohort study of patients with documented,
      monochromatic near-infrared phototherapy (MIRE)-mediated, symptomatic reversal of
      DPN. SETTING: responses to a health status questionnaire following symptomatic
      reversal of DPN. PATIENTS: 252 patients (mean age 76 years) provided health
      information following symptomatic reversal of diabetic neuropathy (mean duration
      8.6 months). MAIN RESULTS: incidence of falls and fear of falling decreased
      within 1 month after reversal of peripheral neuropathy and remained low after 1
      year. Likewise, improved ADL were evident soon after reversal of peripheral
      neuropathy and showed further improvement after 1 year. Overall, reversal of
      peripheral neuropathy in a clinician's office and subsequent use of MIRE at home
      was associated with a 78% reduction in falls, a 79% decrease in balance-related
      fear of falling and a 72% increase in ADL (P < 0.0002 for all results).
      CONCLUSIONS: reversal of peripheral neuropathy is associated with an immediate
      reduction in the absolute number of falls, a reduced fear of falling and improved
      ADL. These results suggest that symptomatic reversal of diabetic neuropathy will
      have a substantial favourable, long-term socioeconomic impact on patients with
      DPN and the Medicare system, and improve the quality of life for elderly patients
      with diabetes and peripheral neuropathy.

PMID- 16303776
TI  - Intravenous immunoglobulin for resistant Clostridium difficile infection.
AB  - Clostridium difficile (CD)-associated diarrhoea and colitis may relapse in up to
      20% of treated patients. We present a patient who failed to respond over a 6
      month period to treatment either singly or in combination with metronidazole,
      vancomycin, rifampicin, cholestyramine and probiotics. Her diarrhoea rapidly
      resolved after a 3-day course of intravenous immunoglobulin. This treatment may
      compensate for a failed immune response to CD toxin and should be considered for
      relapsing CD-associated diarrhoea where there is no response to conventional
      treatment strategies.

PMID- 16303777
TI  - A systematic approach to managing pregnant dialysis patients--the importance of
      an intensified haemodiafiltration protocol.

PMID- 16303778
TI  - Dentistry, neurology and nephrology--what is the connection?

PMID- 16303779
TI  - Goodpasture's syndrome with massive pulmonary haemorrhage in the absence of
      circulating anti-GBM antibodies?

PMID- 16303780
TI  - Effects on inflammatory and nutritional markers of haemodiafiltration with online
      regeneration of ultrafiltrate (HFR) vs online haemodiafiltration: a cross-over
      randomized multicentre trial.
AB  - BACKGROUND: HFR [double chamber haemodiafiltration (HDF) with reinfusion of
      regenerated ultrafiltrate] is a novel dialytic method which combines the
      processes of diffusion, convection and adsorbance. In this technique an adsorbent
      cartridge of resin and charcoal may regenerate the ultrafiltrate suggesting its
      use as an endogenous substitution fluid. The aim of this multicentre randomized
      cross-over study was to compare HFR to online HDF in terms of inflammatory and
      nutritional parameters. METHODS: After a 1 month run-in period of standard
      bicarbonate dialysis (HD) with a synthetic membrane, 25 chronic dialytic patients
      were randomized (A-B or B-A) to be treated by HFR (A) with a two-chamber filter
      (SG 8 Plus - high permeability Polysulphone HF 0.7 m2 + SMC 1.95 sqm; Bellco,
      Mirandola, Italy) or by online sterile bicarbonate HDF. Each study period of 4
      months was separated by 1 month of HD and the entire length of the study was 10
      months. CRP levels were measured by a highly sensitive nephelometric assay (Dade,
      Behring) with a sensitivity of 0.1 microg/ml. Cytokine concentrations were
      determined by EIA [Interleukin (IL) 6, Biosource, USA and IL-10 Bender MED
      Systems, Vienna]. The sensitivity thresholds were < 5 pg/ml for IL-6 and < 8
      pg/ml for IL-10. Serum leptin was determined with a ELISA method (Biosource,
      USA). All parameters were determined monthly in patients starting a midweek
      dialytic session. RESULTS: Plasma CRP and IL-6 were significantly reduced during
      the 4 months of HFR and HDF: CRP from 8.0 +/- 3.2 to 5.6 +/- 3.4 mg/l with HFR (P
      < 0.05) and from 9.4 +/- 4.3 to 5.9 +/- 3.9 mg/l with HDF (P < 0.05). IL-6
      decreased from 14.8 +/- 6.3 to 10.1 +/- 3.2 with HFR (P < 0.02) and from 12.1 +/-
      4.2 to 9.6 +/- 3.7 with HDF (P = ns) with a percentage decrease after 4 months of
      32% with HFR vs 21% with HDF. During the 1 month wash-out period with HD, CRP
      increased from 5.7 +/- 3.6 to 8.7 +/- 3.9 mg/l (P < 0.01) and IL-6 from 10 +/-
      3.4 to 13.5 +/- 5.2 pg/ml (P < 0.01). A significant increase in IL-10 was
      detected either in HFR (from 4.8 +/- 2.1 to 6.89 +/- 1.7 pg/ml) and in HDF (from
      3.3 +/- 1.7 to 8.95 +/- 4.3 pg/ml; P < 0.05) after 4 months. No significant
      variation in serum leptin levels were observed during the study. CRP and IL-6
      were highly correlated (r = 0.54; P < 0.001) as was serum albumin and prealbumin
      (r = 0.39; P < 0.001). Serum albumin was negatively correlated with CRP (r = 
      0.26; P < 0.01) and IL-6 (r = -0.19; P < 0.05); serum prealbumin was correlated
      with IL-6 (r = 0.37; P < 0.001) and with CRP (r = 0.24; P < 0.01). CONCLUSIONS:
      Haemodiafiltration with online regeneration of ultrafiltrate and online HDF are
      highly biocompatible techniques and no significant difference between HFR and
      online HDF was observed in terms of reduction of inflammatory markers. Further
      studies with a longer follow-up are needed to evaluate the clinical relevance of
      the online endogenous reinfusion to counteract the chronic inflammatory state of
      the uraemic patient.

PMID- 16303781
TI  - A novel WT1 missense mutation presenting with Denys-Drash syndrome and cortical
      atrophy.

PMID- 16303783
TI  - Using qualitative and quantitative formative research to develop tailored
      nutrition intervention materials for a diverse low-income audience.
AB  - More effective nutrition education to reach low-income and ethnic minority
      populations is needed. As part of a project to develop a tailored nutrition
      education intervention to meet the needs of low-income Hispanics and non
      Hispanics, complementary, mixed methods of formative research were used to
      determine specific characteristics of the target population. The aim was to
      ensure that the full array of nutrition messages would be comprehensive enough to
      effectively tailor to the level of the individual. Barriers to healthy eating
      were delineated for three main dietary behaviors (number of items delineated in
      parentheses): lowering fat (11), increasing fruit (8) and increasing vegetables
      (6). Information was also collected regarding motivators for healthy eating (5),
      situational barriers to making healthy choices (4), other nutrition-related
      interests (8) and typical eating habits and food-related choices of the target
      audience.

PMID- 16303782
TI  - Hypertension in dialysed children: the prevalence and therapeutic approach in
      Poland--a nationwide survey.
AB  - BACKGROUND: The aim of this nationwide analysis was to assess the incidence and
      current treatment profile of arterial hypertension in children undergoing chronic
      haemodialysis or peritoneal dialysis and attitudes of paediatric nephrologists
      towards the choice of antihypertensive drugs in their patients. METHODS: The
      study group consisted of 134 children (89 males, 45 females, mean age 10.7+/-5
      years) from all 13 paediatric dialysis centres in Poland. The data were gathered
      through a questionnaire for each patient dialysed in November 2004. RESULTS: The
      overall incidence of hypertension in the study group was 55% (74 of 134 patients;
      47 males, 27 females). The incidence rate was similar in boys and girls (53 vs
      60%) and in those on haemodialysis and peritoneal dialysis (56 vs 54%). Chronic
      glomerulonephritis as an underlying renal disease was significantly more frequent
      in the hypertensive than in the normotensive subjects (37 vs 10%, P = 0.004).
      Residual urine output was higher in normotensives (41 vs 10 ml/kg body weight; P
      < 0.001). Among those treated with antihypertensives: 32% were treated by
      monotherapy, 36% received two drugs, 22% received three drugs, while 7% received
      > or = 4 drugs. The therapy was effective in only 57% of subjects. We observed no
      differences in biochemical and clinical parameters between those who responded to
      the therapy and those who failed to do so. Calcium channel blockers constituted
      the most frequently administered class of drugs [73% of children; in 43 out of 48
      (90%) combined with other drugs, but in 11 out of 24 (46%) as a monotherapy]. In
      monotherapy, angiotensin-converting enzyme inhibitors and calcium channel
      blockers were administered most frequently. CONCLUSION: We conclude that the
      incidence of hypertension in dialysis children in Poland is high (55%). The
      effectiveness of antihypertensive treatment is rather low (58%) and the choice of
      drugs is limited.

PMID- 16303784
TI  - AIDS education for Tanzanian youth: a mediation analysis.
AB  - Mediation analysis is a statistical technique that can be used to identify
      mechanisms by which intervention programs achieve their effects. This paper
      presents the results of a mediation analysis of Ngao, an acquired
      immunodeficiency syndrome (AIDS) education program that was implemented with
      school children in Grades 6 and 7 in Tanzania in the mid-1990s and evaluated
      using a controlled, group-randomized trial. The study examined which variables
      mediated the effect Ngao had in regard to (i) fostering positive attitudes
      towards people living with AIDS and (ii) decreasing intentions to be sexually
      active in the near future. Data from students who participated in a baseline and
      12-month follow-up survey (n = 814) were analyzed. Results indicate that
      increasing exposure to AIDS information and increasing knowledge about human
      immunodeficiency virus transmission/prevention were significant mediators of the
      intervention's effect on alleviating the stigma associated with people living
      with AIDS. Moreover, encouraging more restrictive social norms about sexual
      intercourse was a significant mediator of the intervention's effect on decreasing
      students' intentions to be sexually active in the near future. Implications for
      future AIDS education programs for school children in this part of Africa
      designed to achieve similar goals are discussed.

PMID- 16303785
TI  - Endovascular treatment for thoracic aortic dissection: the better solution?

PMID- 16303786
TI  - Different B-cell populations are responsible for the peripheral and intrathecal
      antibody production in neuroborreliosis.
AB  - The diagnosis of neuroborreliosis (NB)--a serious complication of Lyme disease-
      relies on demonstration of intrathecal borrelia antibody production. We
      hypothesized that if a qualitative difference between the cerebrospinal fluid and
      the serum immunoblot-banding patterns was observed, then the borrelia antibodies
      found in the CSF could not be the result of leakage of serum antibodies to the
      CSF due to blood-brain barrier damage, but rather had to be produced
      intrathecally. CSF/serum pairs from 69 NB patients and from 85 control patients
      with other neurological disorders were investigated. All samples were tested
      blindly by immunoblot and a commercial capture ELISA kit for NB. The concordance
      between the two methods was 85.7%. When using the other method as reference, the
      accuracy of the two assays in the two patient materials was similar: 80% for
      sensitivity and 95% for specificity. Four types of comparative immunoblot-banding
      patterns that reflected intrathecal borrelia antibody synthesis were
      distinguished. The study showed that a simple comparison between the immunoblot
      pattern of serum and CSF samples allows for a reliable diagnosis of NB by
      demonstration of intrathecal antibody production. This is the first study to show
      that a qualitative difference of the antibody response between the immune
      response of serum and CSF is a rule. The findings also imply that partly
      different B-cell populations are responsible for the antibody production in the
      blood and in the central nervous system. In addition, our observation provides
      possible implications for other infectious diseases with CNS involvement.

PMID- 16303788
TI  - Low birth weight and prematurity in the neonatal unit of a maternity and
      pediatrics hospital in Iraq.

PMID- 16303787
TI  - Maturation of human monocyte-derived dendritic cells (MoDCs) in the presence of
      prostaglandin E2 optimizes CD4 and CD8 T cell-mediated responses to protein
      antigens: role of PGE2 in chemokine and cytokine expression by MoDCs.
AB  - Prostaglandin E2 (PGE2) acts in synergy with other inflammatory stimuli such as
      tumor necrosis factor (TNF) to induce the maturation of migratory-type monocyte
      derived dendritic cells (MoDCs). However, PGE2 has been reported to inhibit IL
      12p70 production by MoDCs and to promote the generation of Th2 T cell responses.
      We demonstrate here that the addition of PGE2 to TNF for the maturation of MoDCs
      enhanced CD4 and CD8 T cell proliferative responses to neoantigen and recall
      antigen, and enhanced Th1-type responses. The increased stimulatory capacity of
      MoDCs matured with PGE2 was associated with a fully mature, migratory-type MoDC
      phenotype and more rapid down-regulation of the expression of inflammatory
      chemokines, with up-regulated expression of the constitutive chemokines TARC and
      MDC. In addition, although MoDCs matured with TNF and PGE2 selectively produced
      the inhibitory IL-12p40 subunit at steady state, they were able to produce the
      bioactive IL-12p70 heterodimer after stimulation with CD40 ligand and/or IFN
      gamma. Despite increased IL-6 mRNA expression, MoDCs matured with PGE2 did not
      overcome the suppressive effects of CD4+ CD25+ T cells in allogeneic mixed
      lymphocyte reactions. In conclusion, MoDCs matured in the presence of PGE2
      display characteristics of more efficient antigen-presenting cells that might be
      optimal for use in cancer vaccine-based clinical trials.

PMID- 16303789
TI  - Enzymatic activity of Campylobacter jejuni hippurate hydrolase.
AB  - The hippurate hydrolase enzyme of Campylobacter jejuni was expressed in
      Escherichia coli as a six-histidine-tagged fusion protein. The purified
      recombinant enzyme was characterized to gain an understanding of the structure
      and activity of the hippurate hydrolase. The recombinant enzyme had a native
      molecular mass of 193+/- 11 kDa a reduced molecular mass of 42.4+/- 0.8 kDa, and
      possessed 1.98+/- 0.68 molecules of zinc per enzyme subunit molecule, suggesting
      that it was a homotetramer with two associated zinc ions. The enzyme was a
      metallocarboxypeptidase that was sensitive to silver, copper and ferrous ions,
      and displayed optimal activity at pH 7.5 and 50 degrees C. It hydrolyzed
      carboxypeptidase substrates in vitro, displaying its highest activity against N
      benzoyl-linked small aliphatic amino acids. A high proportion of the enzyme
      structure consisted of highly ordered alpha-helix and beta-sheet sequences. An
      alignment of the amino acid sequence of the hippurate hydrolase enzyme with those
      of related enzymes with similar activities revealed several conserved amino
      acids, which might be involved in enzyme catalysis or metal ion binding for the
      enzyme. Site-directed mutagenesis of the recombinant enzyme demonstrated that the
      Asp(76), Aps(104), Glu(134), Glu(135), His(161) and His(356) positions were
      important for the catalytic activity of the enzyme.

PMID- 16303790
TI  - Brief intervention in alcohol-positive traffic casualties: is it worth the
      effort?
AB  - AIMS: This study aimed at testing the effectiveness of a brief motivational
      intervention (BI) compared with a minimal intervention (MI) for reducing alcohol
      consumption in adult, alcohol-positive traffic casualties. METHODS: Patients were
      recruited at the emergency room of a trauma hospital and screened for alcohol by
      a qualitative saliva test (positive from a blood alcohol concentration of 0.02
      g/l). Positive patients (13.3%) who accepted entering the study were randomly
      allocated into BI and MI. Baseline assessment was the same for all patients.
      Blind telephone follow-ups were performed at months 3, 6, and 12, and results
      were analysed by protocol and by intention-to-treat analysis. RESULTS: After 1
      year of follow-up, 67% of the patients had reduced their consumption, the
      percentage of heavy drinkers had dropped by 47%, and 62% of baseline AUDIT-C
      positive patients (hazardous drinkers) had become negative. Binge drinking
      dropped significantly (P < 0.05). Results at month 12 were in line with the
      previous ones. CONCLUSIONS: The effectiveness of BI compared with MI has not been
      verified, but a significant reduction in consumption has been observed in the
      whole sample, without significant differences by type of intervention. The
      persistence and dimension of changes suggest a real effect of both interventions,
      although the lack of a pure control group does not allow definitive conclusions.
      Traffic casualties are in a teachable moments to benefit from easy and cheap
      interventions.

PMID- 16303791
TI  - Biological markers as a predictor for response and prognosis of unresectable
      gastric cancer patients treated with irinotecan and cisplatin.
AB  - BACKGROUND: Previously we reported that immunohistochemical examination of p53,
      bcl-2, glutathione S-transferase-pi (GST-pi), thymidylate synthase (TS) and
      vascular endothelial growth factor (VEGF) in biopsy samples was a useful method
      for predicting clinical outcome of gastric cancer patients treated with 5
      fluorouracil and cisplatin. Here, we investigated if these biological markers can
      predict chemoresponse and survival of unresectable gastric cancer patients
      treated with irinotecan and cisplatin. METHODS: The subjects were 55 unresectable
      gastric cancer patients treated with irinotecan (70 mg/m(2), Days 1 and 15) and
      cisplatin (80 mg/m(2), Day 1). Expression of p53, bcl-2, VEGF was examined
      immunohistochemically in biopsy samples. RESULTS: The overall response rate and
      the median survival time were 55% (30/55) and 321 days, respectively. Thirty
      patients with intestinal-type adenocarcinoma survived longer than 25 patients
      with diffuse-type (median survival time: 446, 259 days, P = 0.013). The favorable
      phenotypes for chemoresponse were p53-negative, bcl-2-negative and VEGF-positive,
      which were in accordance with previous findings. The response rate was
      significantly correlated with the total number of these favorable phenotypes (P =
      0.043). The 39 patients having 2 or 3 favorable phenotypes (p53-negative, bcl-2
      negative and VEGF-positive) survived longer than the remaining 16 patients
      (median survival time: 444, 259 days, P = 0.021). In the Cox model, the number of
      the favorable phenotypes showed a tendency to correlate with survival after
      adjustment for potentially prognostic factors such as histological type or
      performance status (P = 0.070). CONCLUSIONS: Immunohistochemical examination of
      biological markers may be useful in predicting the clinical outcome of
      unresectable gastric cancer patients treated with irinotecan and cisplatin.

PMID- 16303792
TI  - Phase II randomized trial of tri-weekly versus days 1 and 8 weekly docetaxel as a
      second-line treatment of advanced non-small cell lung cancer.
AB  - BACKGROUND: For orientals, titrating doses of docetaxel (60-66 mg/m(2)) have
      shown equal effectiveness and fewer side effects as a second-line chemotherapy
      for patients with advanced non-small cell lung cancer (NSCLC). Under such doses,
      there were no comparative data between classic tri-weekly and Days 1 and 8 weekly
      schedules. METHODS: This Phase II randomized prospective study was designed to
      compare the toxicity profile, efficacy and quality-of-life (QOL) between these
      two schedules of docetaxel in the treatment of previously treated patients with
      advanced NSCLC. Fifty patients were randomized to docetaxel arm A (66 mg/m(2) Day
      1) and B (33 mg/m(2) Days 1 and 8) given every 3 weeks. RESULTS: The overall
      response rates (ORRs) were 12 and 24% in arm A and B, respectively (P = 0.46),
      and disease control rates were 52 and 48%. The median time-to-progression (TTP)
      was 11.3 and 12.7 weeks and median survivals were 33.4 and 27.6 weeks,
      respectively. Both arms have same 1 year (36%) and 2 year survivals (12%). Arm A
      had significantly higher neutropenia but less compromised QOL. In this study, the
      response of second-line chemotherapy was significantly better in the group that
      was response to front-line chemotherapy (P = 0.032). CONCLUSIONS: While Days 1
      and 8 weekly docetaxel schedules show higher ORR and less hematological toxicity,
      there is no advantage to tri-week schedule in terms of TTP and survival, but more
      compromised QOL.

PMID- 16303793
TI  - Phase I study of fixed dose rate infusion of gemcitabine in patients with
      unresectable pancreatic cancer.
AB  - OBJECTIVE: The purpose of this study was to determine the feasible dose of
      gemcitabine when administered as a fixed dose rate infusion (10 mg/m(2)/min) on a
      weekly schedule to Japanese patients with unresectable advanced pancreatic
      cancer. METHODS: Patients were required to have histologically or cytologically
      proven locally advanced or metastatic pancreatic cancer for which they had
      received no previous chemotherapy. Gemcitabine was administered intravenously
      weekly for three consecutive weeks every 4 weeks. Patients at three dose levels
      were scheduled to receive escalating doses of gemcitabine: 1000 mg/m(2) over 100
      min (Level 1), 1200 mg/m(2) over 120 min (Level 2) and 1500 mg/m(2) over 150 min
      (Level 3). RESULTS: A total of 16 patients were enrolled in this study between
      December 2003 and September 2004. Maximum-tolerated dose was not reached during
      the first course. Dose-limiting toxicity was Grade 4 neutropenia. Grade 3 or 4
      neutropenia was observed at Level 3 in all six patients in the first course, and
      administration of gemcitabine on Day 8 or 15 was skipped in all six patients. Non
      hematologic toxicity was mild and the most common symptoms were anorexia, nausea
      and vomiting. Partial response was achieved in 1 of the 17 patients (7%). Median
      overall survival was 7.3 months. CONCLUSIONS: Gemcitabine administered at a rate
      of 10 mg/m(2)/min was tolerated up to 1500 mg/m(2), but 1200 mg/m(2) represented
      a more appropriate recommended dose in further studies owing to neutropenia in
      Japanese patients with advanced pancreatic cancer.

PMID- 16303794
TI  - REDfly: a Regulatory Element Database for Drosophila.
AB  - Bioinformatics studies of transcriptional regulation in the metazoa are
      significantly hindered by the absence of readily available data on large numbers
      of transcriptional cis-regulatory modules (CRMs). Even the richly annotated
      Drosophila melanogaster genome lacks extensive CRM information. We therefore
      present here a database of Drosophila CRMs curated from the literature complete
      with both DNA sequence and a searchable description of the gene expression
      pattern regulated by each CRM. This resource should greatly facilitate the
      development of computational approaches to CRM discovery as well as
      bioinformatics analyses of regulatory sequence properties and evolution.

PMID- 16303795
TI  - Describing ancient horizontal gene transfers at the nucleotide and gene levels by
      comparative pathogenicity island genometrics.
AB  - MOTIVATION: Lateral gene transfer is a major mechanism contributing to bacterial
      genome dynamics and pathovar emergence via pathogenicity island (PAI) spreading.
      However, since few of these genomic exchanges are experimentally reproducible, it
      is difficult to establish evolutionary scenarios for the successive PAI
      transmissions between bacterial genera. Methods initially developed at the gene
      and/or nucleotide level for genomics, i.e. comparisons of concatenated sequences,
      ortholog frequency, gene order or dinucleotide usage, were combined and applied
      here to homologous PAIs: we call this approach comparative PAI genometrics.
      RESULTS: YAPI, a Yersinia PAI, and related islands were compared with measure
      evolutionary relationships between related modules. Through use of our genometric
      approach designed for tracking codon usage adaptation and gene phylogeny, an
      ancient inter-genus PAI transfer was oriented for the first time by
      characterizing the genomic environment in which the ancestral island emerged and
      its subsequent transfers to other bacterial genera.

PMID- 16303796
TI  - A bi-dimensional regression tree approach to the modeling of gene expression
      regulation.
AB  - MOTIVATION: The transcriptional regulation of a gene depends on the binding of
      cis-regulatory elements on its promoter to some transcription factors and the
      expression levels of the transcription factors. Most existing approaches to
      studying transcriptional regulation model these dependencies separately, i.e.
      either from promoters to gene expression or from the expression levels of
      transcription factors to the expression levels of genes. Little effort has been
      devoted to a single model for integrating both dependencies. RESULTS: We propose
      a novel method to model gene expression using both promoter sequences and the
      expression levels of putative regulators. The proposed method, called bi
      dimensional regression tree (BDTree), extends a multivariate regression tree
      approach by applying it simultaneously to both genes and conditions of an
      expression matrix. The method produces hypotheses about the condition-specific
      binding motifs and regulators for each gene. As a side-product, the method also
      partitions the expression matrix into small submatrices in a way similar to bi
      clustering. We propose and compare several splitting functions for building the
      tree. When applied to two microarray datasets of the yeast Saccharomyces
      cerevisiae, BDTree successfully identifies most motifs and regulators that are
      known to regulate the biological processes underlying the datasets. Comparing
      with an existing algorithm, BDTree provides a higher prediction accuracy in cross
      validations.

PMID- 16303797
TI  - A structure and evolution-guided Monte Carlo sequence selection strategy for
      multiple alignment-based analysis of proteins.
AB  - MOTIVATION: Various multiple sequence alignment-based methods have been proposed
      to detect functional surfaces in proteins, such as active sites or protein
      interfaces. The effect that the choice of sequences has on the conclusions of
      such analysis has seldom been discussed. In particular, no method has been
      discussed in terms of its ability to optimize the sequence selection for the
      reliable detection of functional surfaces. RESULTS: Here we propose, for the case
      of proteins with known structure, a heuristic Metropolis Monte Carlo strategy to
      select sequences from a large set of homologues, in order to improve detection of
      functional surfaces. The quantity guiding the optimization is the clustering of
      residues which are under increased evolutionary pressure, according to the sample
      of sequences under consideration. We show that we can either improve the overlap
      of our prediction with known functional surfaces in comparison with the sequence
      similarity criteria of selection or match the quality of prediction obtained
      through more elaborate non-structure based-methods of sequence selection. For the
      purpose of demonstration we use a set of 50 homodimerizing enzymes which were co
      crystallized with their substrates and cofactors.

PMID- 16303798
TI  - Statistical estimation of gene expression using multiple laser scans of
      microarrays.
AB  - We propose a statistical model for estimating gene expression using data from
      multiple laser scans at different settings of hybridized microarrays. A
      functional regression model is used, based on a non-linear relationship with both
      additive and multiplicative error terms. The function is derived as the expected
      value of a pixel, given that values are censored at 65 535, the maximum
      detectable intensity for double precision scanning software. Maximum likelihood
      estimation based on a Cauchy distribution is used to fit the model, which is able
      to estimate gene expressions taking account of outliers and the systematic bias
      caused by signal censoring of highly expressed genes. We have applied the method
      to experimental data. Simulation studies suggest that the model can estimate the
      true gene expression with negligible bias. AVAILABILITY: FORTRAN 90 code for
      implementing the method can be obtained from the authors.

PMID- 16303799
TI  - Detecting periodic patterns in unevenly spaced gene expression time series using
      Lomb-Scargle periodograms.
AB  - MOTIVATION: Periodic patterns in time series resulting from biological
      experiments are of great interest. The commonly used Fast Fourier Transform (FFT)
      algorithm is applicable only when data are evenly spaced and when no values are
      missing, which is not always the case in high-throughput measurements. The choice
      of statistic to evaluate the significance of the periodic patterns for unevenly
      spaced gene expression time series has not been well substantiated. METHODS: The
      Lomb-Scargle periodogram approach is used to search time series of gene
      expression to quantify the periodic behavior of every gene represented on the DNA
      array. The Lomb-Scargle periodogram analysis provides a direct method to treat
      missing values and unevenly spaced time points. We propose the combination of a
      Lomb-Scargle test statistic for periodicity and a multiple hypothesis testing
      procedure with controlled false discovery rate to detect significant periodic
      gene expression patterns. RESULTS: We analyzed the Plasmodium falciparum gene
      expression dataset. In the Quality Control Dataset of 5080 expression patterns,
      we found 4112 periodic probes. In addition, we identified 243 probes with
      periodic expression in the Complete Dataset, which could not be examined in the
      original study by the FFT analysis due to an excessive number of missing values.
      While most periodic genes had a period of 48 h, some had a period close to 24 h.
      Our approach should be applicable for detection and quantification of periodic
      patterns in any unevenly spaced gene expression time-series data.

PMID- 16303800
TI  - Maximum significance clustering of oligonucleotide microarrays.
AB  - MOTIVATION: Affymetrix high-density oligonucleotide microarrays measure the
      expression of DNA transcripts using probesets, i.e. multiple probes per
      transcript. Usually, these multiple measurements are transformed into a single
      probeset expression level before data analysis proceeds; any information on
      variability is lost. In this paper we demonstrate how individual probe
      measurements can be used in a statistic for differential expression. Furthermore,
      we show how this statistic can serve as a criterion for clustering microarrays.
      RESULTS: A novel clustering algorithm using this maximum significance criterion
      is demonstrated to be more efficient with the measured data than competing
      techniques for dealing with repeated measurements, especially when the sample
      size is small.

PMID- 16303801
TI  - Commentary: sunlight, vitamin D, and the cancer connection revisited.

PMID- 16303802
TI  - Commentary: culture in epidemiology--the 800 pound gorilla?

PMID- 16303803
TI  - Commentary: taking culture seriously in health research.

PMID- 16303804
TI  - Is modern Western culture a health hazard?

PMID- 16303805
TI  - Commentary: from epidemiology to molecular biology--vitamin D and colorectal
      cancer prevention.

PMID- 16303806
TI  - Commentary: time for public health action on vitamin D for cancer risk reduction.

PMID- 16303807
TI  - Commentary: vitamin D and colorectal cancer--twenty-five years later.

PMID- 16303808
TI  - Commentary: progress of a paradigm.

PMID- 16303809
TI  - Do sunlight and vitamin D reduce the likelihood of colon cancer?

PMID- 16303810
TI  - The epidemiology of chronic syndromes that are frequently unexplained: do they
      have common associated factors?
AB  - BACKGROUND: Syndromes for which no physical or pathological changes can be found
      tend to be researched and managed in isolation although hypotheses suggest that
      they may be one entity. The objectives of our study were to investigate the co
      occurrence, in the general population, of syndromes that are frequently
      unexplained and to evaluate whether they have common associated factors. METHODS:
      We conducted a population-based cross-sectional survey that included 2,299
      subjects who were registered with a General Medical Practice in North-west
      England and who completed full postal questionnaires (response rate 72%). The
      study investigated four chronic syndromes that are frequently unexplained:
      chronic widespread pain, chronic oro-facial pain, irritable bowel syndrome, and
      chronic fatigue. Validated instruments were used to measure the occurrence of
      syndromes and to collect information on a variety of associated factors:
      demographic (age, gender), psychosocial (anxiety, depression, illness behaviour),
      life stressors, and reporting of somatic symptoms. RESULTS: We found that 587
      subjects (27%) reported one or more syndromes: 404 (18%) reported one, 134 (6%)
      reported two, 34 (2%) reported three, and 15 (1%) reported all four syndromes.
      The occurrence of multiple syndromes was greater than would be expected by chance
      (P < 0.001). There were factors that were common across syndromes: female gender
      [odds ratio (OR) = 1.8; 95% confidence interval (95% CI) 1.5-2.2], high levels of
      aspects of health anxiety like health worry preoccupation (OR = 3.5; 95% CI 2.8
      4.4) and reassurance seeking behaviour (OR = 1.4; 95% CI 1.1-1.7), reporting of
      other somatic symptoms (OR = 3.6; 95% CI 2.9-4.4), and reporting of recent
      adverse life events (OR = 2.3; 95% CI 1.9-2.8). CONCLUSION: This study has shown
      that chronic syndromes that are frequently unexplained co-occur in the general
      population and share common associated factors. Primary care practitioners need
      to be aware of these characteristics so that management is appropriate at the
      outset.

PMID- 16303811
TI  - Maternal cigarette smoking and the risk of pregnancy-induced hypertension and
      eclampsia.
AB  - BACKGROUND: Although previous studies have found that maternal smoking decreases
      the risk of pregnancy-induced hypertension (PIH), the difference of this effect
      between primiparous and multiparous women has not been well studied and the
      results of the exposure-response relationships between maternal smoking and PIH
      are inconsistent. No previous study has specifically examined the relationship
      between maternal smoking and eclampsia. METHODS: We analysed data from a
      population-based retrospective cohort study of 3 153 944 singleton pregnancies in
      the US. The data were derived from the national linked birth/infant mortality
      database for 1998. Multiple logistic regressions were used to describe the
      relationship between cigarette smoking and PIH and eclampsia. RESULTS: The
      adjusted odds ratios (ORs) [95% confidence intervals (95% CIs)] for PIH were 0.80
      (0.77-0.83) for primiparous women and 0.81 (0.78-0.83) for multiparous women
      among smokers compared with non-smokers. The corresponding adjusted ORs (95% CIs)
      for eclampsia were 0.74 (0.66-0.82) and 0.75 (0.68-0.83), respectively. For PIH,
      the adjusted OR (95% CI) for smokers vs non-smokers were 0.82 (0.79-0.86), 0.81
      (0.78-0.83), 0.80 (0.77-0.83), and 0.88 (0.79-0.98), respectively, for 1-5, 6-10,
      11-20, and >20 cigarettes per day (test for trend: P = 0.86). The corresponding
      figures for eclampsia were 0.85 (0.75-0.95), 0.74 (0.66-0.82), 0.68 (0.58-0.78),
      and 0.73 (0.49-1.04), respectively (test for trend: P = 0.02). CONCLUSION:
      Maternal cigarette smoking decreases the risk of PIH and eclampsia, with a
      significant inverse exposure-response relationship apparent for eclampsia.

PMID- 16303812
TI  - Selection bias and its implications for case-control studies: a case study of
      magnetic field exposure and childhood leukaemia.
AB  - Based on the epidemiological association between residential exposure to
      extremely low frequency-magnetic fields (ELF-MF) and childhood leukaemia, the
      International Agency for Research on Cancer classified ELF-MF as a possible human
      carcinogen. Since clear supportive laboratory evidence is lacking and biophysical
      plausibility of carcinogenicity of MFs is questioned, a causal relationship
      between childhood leukaemia and magnetic field exposure is not established. Among
      the alternative explanations, selection bias in epidemiological studies of MFs
      seems to be the most plausible hypothesis. In reviewing the epidemiological
      literature on ELF-MF exposure and childhood leukaemia, we found evidence both for
      and against the existence of selection bias. To evaluate the potential for
      selection bias, we examined the relationship of socioeconomic status to subject
      participation and exposure to MFs. We find that, often, reporting of selection
      processes in itself is biased and incomplete, making the interpretation and
      evaluation of a potential for bias difficult. However, if present, such a bias
      would have wide implications for case-control studies in general. We call for
      better reporting and for evaluation of the potential for selection bias in all
      case-control studies, as well as, for the development of novel methods in control
      selection and recruitment.

PMID- 16303813
TI  - Commentary: socioeconomic position and the risk of type 2 diabetes.

PMID- 16303814
TI  - Commentary: H. pylori infection in early life and the problem of imperfect tests.

PMID- 16303815
TI  - Under-representation of the oldest people in NSAID therapy trials.

PMID- 16303817
TI  - Pulsed low-intensity ultrasound therapy for chronic lateral epicondylitis: a
      randomized controlled trial.
AB  - OBJECTIVES: Pulsed low-intensity ultrasound therapy (LIUS) has been found to be
      beneficial in accelerating fracture healing and has produced positive results in
      animal tendon repair. In the light of this we undertook a randomized, double
      blind, placebo controlled trial to assess the effectiveness of LIUS vs placebo
      therapy daily for 12 weeks in patients with chronic lateral epicondylitis (LE).
      METHODS: Patients with LE of at least 6 weeks' duration were recruited from
      general practice, physiotherapy and rheumatology clinics, and had to have failed
      at least one first-line treatment including non steroidal anti-inflammatory drugs
      (NSAIDs) and corticosteroid injection. Participants were assigned either active
      LIUS or placebo. Treatment was self-administered daily for 20 min over a 12-week
      period. The primary end-point was a 50% improvement from baseline in elbow pain
      measured at 12 weeks using a patient-completed visual analogue scale. RESULTS:
      Fifty-five subjects aged 18-80 were recruited over a 9-month period. In the
      active group 64% (16/25) achieved at least 50% improvement from baseline in elbow
      pain at 12 weeks compared with 57% (13/23) in the placebo group (difference of
      7%; 95% confidence interval -20 to 35%). However, this was not statistically
      significant (chi(2) = 0.28, P = 0.60). CONCLUSION: In this study LIUS was no more
      effective for a large treatment effect than placebo for recalcitrant LE. This is
      in keeping with other interventional studies for the condition.

PMID- 16303818
TI  - Monocyte chemoattractant protein-4 (MCP-4)/CCL13 is highly expressed in cartilage
      from patients with rheumatoid arthritis.
AB  - OBJECTIVES: To study the role of monocyte chemoattractant protein-4 (MCP-4)/CCL13
      in the pathogenesis of rheumatoid arthritis (RA), we analysed the expression of
      MCP-4/CCL13 in chondrocytes, synovial fluid and serum from patients with RA and
      investigated the effect of MCP-4/CCL13 on the proliferation of synovial cells.
      METHODS: Human articular cartilage specimens were obtained from joints from RA
      and osteoarthritis (OA) patients and normal joints (controls). Transcript levels
      of MCP-4 in cartilage were determined by real-time polymerase chain reaction.
      Protein levels were measured by enzyme-linked immunoassay. Cultured fibroblast
      like synoviocytes (FLS) were treated with various concentrations of recombinant
      MCP-4/CCL13 protein, and cell proliferation was evaluated with a viability assay.
      RESULTS: The gene expression of MCP-4 was significantly higher in cartilage from
      RA patients than in that from OA patients (P = 0.00902) and in normal cartilage
      (P = 0.00902). The concentration of MCP-4/CCL13 protein in serum from RA patients
      (mean 94.7 +/- 37.6 pg/ml) was significantly higher than in serum from OA
      patients (mean 49.2 +/- 31.2 pg/ml, P = 0.0051) and controls (mean 32.6 +/- 23.9
      pg/ml, P = 0.0001). The concentration of MCP-4/CCL13 protein in synovial fluid
      from RA patients (mean 247.2 +/- 161.2 pg/ml) was also significantly higher than
      in that from OA patients (mean 29.6 +/- 50.5 pg/ml, P = 0.000019). Moreover, MCP
      4/CCL13 enhanced the proliferation of FLS in a dose-dependent manner.
      CONCLUSIONS: MCP-4/CCL13 is highly expressed in RA joints at the mRNA and protein
      levels. Our results suggest that MCP-4/CCL13 is secreted from chondrocytes and
      activates the proliferation of rheumatoid synovial cells, thereby leading to
      joint destruction in RA.

PMID- 16303820
TI  - Dementia associated with antiphospholipid antibodies.

PMID- 16303821
TI  - Serum lipid levels in Sjogren's syndrome.
AB  - OBJECTIVES: Altered lipid levels may occur in autoimmune diseases, for example
      low cholesterol levels have been described in rheumatoid arthritis (RA). Serum
      lipid profiles in patients with Sjogren's syndrome (SS) have not been
      investigated. We hypothesized decreased lipid levels in SS patients and an
      inverse relationship with disease activity. METHODS: Serum lipid levels [total
      cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and
      triglycerides] and additional data regarding disease measures (clinical
      immunology parameters, focus score from labial salivary gland biopsy, salivary
      flow and ophthalmological measures) were available for 46 primary SS patients and
      12 xerostomic controls. RESULTS: Significant differences between SS patients and
      controls means (s.d.) were seen for HDL (P = 0.04) and total cholesterol (P =
      0.02). LDL (P = 0.12) and triglyceride (P = 0.08) levels were not different. In
      SS patients, but not in controls, total cholesterol (P = 0.003) and HDL
      cholesterol (P = 0.003) predicted immunoglobulin G levels. Anti-SSA antibodies
      were related to a lower total cholesterol (P = 0.02) and anti-SSB antibodies to a
      lower HDL cholesterol level (P = 0.0497). CONCLUSIONS: Significant differences
      were seen in serum lipid levels of primary SS patients and these were associated
      with serological measures of inflammation. Our results are comparable to earlier
      findings in RA patients and raise questions related to adverse cardiovascular
      consequences in SS.

PMID- 16303823
TI  - Oxidative stress by glutathione depletion induces osteonecrosis in rats.
AB  - OBJECTIVE: We recently implicated in vivo oxidative stress in the development of
      osteonecrosis in a steroid-induced osteonecrosis model in the domestic rabbit. In
      the present experiment we devised a new non-traumatic model using the rat to
      investigate the relationship between oxidative stress and the development of
      osteonecrosis. METHODS: Seven 24-week-old male Wistar rats were subcutaneously
      injected with the pro-oxidant buthionine sulphoximine (BSO) 500 mg/kg for 14
      consecutive days (group B) and eight rats received injections of vehicle
      (physiological saline; group N). The rats in both groups were killed after 14
      days, and their bilateral femurs were examined histopathologically. Blood levels
      of reduced glutathione (GSH), total cholesterol (T-cho) and triglycerides (TG)
      were also determined. RESULTS: GSH was significantly decreased in group B
      compared with group N (P < 0.01). No significant differences were found in T-cho
      or TG. Osteonecrosis was not detected in any animal in group N in contrast to
      five of seven animals in group B (P < 0.05). CONCLUSION: BSO is an inducer of
      oxidative stress, in particular interfering with the synthesis of GSH in vivo. In
      the present study, GSH levels were markedly reduced by BSO, whereas neither T-cho
      nor TG was significantly changed. The high rate of osteonecrosis noted in group B
      suggests that oxidative stress alone may be sufficient to promote the development
      of osteonecrosis at certain sites.

PMID- 16303826
TI  - Xylem-borne cytokinins: still in search of a role?
AB  - Leaf expansion and xylem cytokinin concentration ([X-CK]) decrease in response to
      nitrogen (N) deprivation. Debate continues over cause, effect, and correlation.
      Supporting studies provide, at best, correlative evidence that [X-CK] controls
      leaf growth in response to N-deprivation, while dissenting studies indicate that
      leaf growth responses to N can be independent of changes in X-CK supply to
      leaves. A model is proposed to evaluate the physiological significance to leaf
      growth of changes in plant and environment N concentrations, and plant CK
      concentrations.

PMID- 16303827
TI  - Microtubule arrays and Arabidopsis stomatal development.
AB  - Microtubule arrays in living cells were analysed during Arabidopsis stomatal
      development in order to more closely define stages in the pathway and contexts
      where intercellular signalling might operate. Arabidopsis stomata are patterned
      iteratively via the orientation of an asymmetric division in a cell located next
      to an existing stoma. It was found that preprophase bands of microtubules (PPBs)
      were correctly placed away from stomata and from two types of precursor cells.
      This suggests that all three cell types participate in an intercellular
      signalling pathway that orients the division site. These and other asymmetric
      divisions in the pathway were preceded by a polarized cytoplasm, with the PPB
      around the nucleus at one end, and the vacuole at the other. PPBs before
      symmetric divisions of guard mother cells (GMCs) were broader than those in
      asymmetric divisions, and the GMC division site was marked by unusual end-wall
      thickenings. This work identifies an accessible system for studying cytoskeletal
      function and provides a foundation for analysing the role of genes involved in
      stomatal development.

PMID- 16303828
TI  - Construction costs, chemical composition and payback time of high- and low
      irradiance leaves.
AB  - The effect of irradiance on leaf construction costs, chemical composition, and on
      the payback time of leaves was investigated. To enable more generalized
      conclusions, three different systems were studied: top and the most-shaded leaves
      of 10 adult tree species in a European mixed forest, top leaves of sub-dominant
      trees of two evergreen species growing in small gaps or below the canopy in an
      Amazonian rainforest, and plants of six herbaceous and four woody species grown
      hydroponically at low or high irradiance in growth cabinets. Daily photon
      irradiance varied 3-6-fold between low- and high-light leaves. Specific leaf area
      (SLA) was 30-130% higher at low light. Construction costs, on the other hand,
      were 1-5% lower for low-irradiance leaves, mainly because low-irradiance leaves
      had lower concentrations of soluble phenolics. Photosynthetic capacity and
      respiration, expressed per unit leaf mass, were hardly different for the low- and
      high-light leaves. Estimates of payback times of the high-irradiance leaves
      ranged from 2-4 d in the growth cabinets, to 15-20 d for the adult tree species
      in the European forest. Low-irradiance leaves had payback times that were 2-3
      times larger, ranging from 4 d in the growth cabinets to 20-80 d at the most
      shaded part of the canopy of the mixed forest. In all cases, estimated payback
      times were less than half the life span of the leaves, suggesting that even at
      time-integrated irradiances lower than 5% of the total seasonal value, investment
      in leaves is still fruitful from a carbon-economy point of view. A sensitivity
      analysis showed that increased SLA of low-irradiance leaves was the main factor
      constraining payback times. Acclimation in the other five factors determining
      payback time, namely construction costs, photosynthetic capacity per unit leaf
      mass, respiration per unit leaf mass, apparent quantum yield, and curvature of
      the photosynthetic light-response-curve, were unimportant when the observed
      variation in each factor was examined.

PMID- 16303829
TI  - Commentary: the PROactive study--the glass is half full.

PMID- 16303830
TI  - Menopause modifies the association of leukocyte telomere length with insulin
      resistance and inflammation.
AB  - CONTEXT: Leukocyte telomere length is inversely correlated with age, insulin
      resistance, serum leptin, and smoking. OBJECTIVE: We explored whether menopausal
      status modifies the relations between leukocyte telomere length and insulin
      resistance. In addition, we examined the effect of menopause on the relation
      between leukocyte telomere length and C-reactive protein (CRP), an index of
      inflammation. DESIGN: This was an observational cohort study. SETTING: The study
      setting was community based. PARTICIPANTS: A total of 1517 women aged 18-79 yr
      selected only for belonging to a twin pair and representative of the general
      population participated in the study. MAIN OUTCOME MEASURE: Leukocyte telomere
      restriction fragment length (TRFL) was measured. RESULTS: Insulin resistance
      (expressed in the homeostasis model assessment), leptin, and CRP were inversely
      correlated with leukocyte TRFL in premenopausal but not postmenopausal women.
      Insulin resistance, CRP, but not leptin independently accounted for variation in
      white blood cell TRFL in premenopausal women. CONCLUSIONS: Menopausal status
      impacts leukocyte telomere length and its relation with insulin resistance and
      inflammation in women.

PMID- 16303831
TI  - Low serum thyrotropin is associated with high plasma fibrinogen.
AB  - BACKGROUND: Elevated plasma fibrinogen levels are associated with an increased
      risk of cardiovascular events. Decreased serum TSH predicts vascular mortality,
      which hypothetically could be explained in part by alterations in the blood
      coagulation system. OBJECTIVE: The objective of this study was to investigate the
      association between thyroid function and plasma fibrinogen levels in a general
      population. DESIGN: The population-based Study of Health in Pomerania was
      performed in a previously iodine-deficient area in Germany, including 4310
      subjects, aged 20-79 yr. Data for 3804 individuals without thyroid disease were
      analyzed. Analysis revealed an association between thyroid function status and
      plasma fibrinogen concentration. RESULTS: Elevated fibrinogen levels (>3.25
      g/liter) were observed in 14 subjects with increased serum TSH levels (32.6%),
      973 euthyroid subjects (28.9%), 158 subjects with decreased serum TSH levels
      (40.7%), and six individuals with overt hyperthyroidism (54.4%). Logistic
      regression analysis revealed decreased serum TSH as an independent risk factor
      for elevated fibrinogen levels (odds ratio, 1.42; 95% confidence interval, 1.12
      1.80). CONCLUSIONS: Thyroid function is associated with plasma fibrinogen.
      Decreased serum TSH is an independent risk factor for elevated plasma fibrinogen
      levels as a possible explanation for the high cardiovascular mortality among
      affected subjects.

PMID- 16303832
TI  - Somatic and germline mosaicism for a mutation of the PHEX gene can lead to
      genetic transmission of X-linked hypophosphatemic rickets that mimics an
      autosomal dominant trait.
AB  - CONTEXT: Familial hypophosphatemic rickets is usually transmitted as an X-linked
      dominant disorder (XLH), although autosomal dominant forms have also been
      observed. Genetic studies of these disorders have identified mutations in PHEX
      and FGF23 as the causes of X-linked dominant disorder and autosomal dominant
      forms, respectively. OBJECTIVE: The objective of the study was to describe the
      molecular genetic findings in a family affected by hypophosphatemic rickets with
      presumed autosomal dominant inheritance. PATIENTS: We studied a family in which
      the father and the elder of his two daughters, but not the second daughter, were
      affected by hypophosphatemic rickets. The pedigree interpretation of the family
      suggested that genetic transmission of the disorder occurred as an autosomal
      dominant trait. METHODS AND RESULTS: Direct nucleotide sequencing of FGF23 and
      PHEX revealed that the elder daughter was heterozygous for an R567X mutation in
      PHEX, rather than FGF23, suggesting that the genetic transmission occurred as an
      X-linked dominant trait. Unexpectedly, the father was heterozygous for this
      mutation. Single-nucleotide primer extension and denaturing HPLC analysis of the
      father using DNA from single hair roots revealed that he was a somatic mosaic for
      the mutation. Haplotype analysis confirmed that the father transmitted the
      genotypes for 18 markers on the X chromosome equally to his two daughters. The
      fact that the father transmitted the mutation to only one of his two daughters
      indicated that he was a germline mosaic for the mutation. CONCLUSIONS: Somatic
      and germline mosaicism for an X-linked dominant mutation in PHEX may mimic
      autosomal dominant inheritance.

PMID- 16303833
TI  - Clinical Review: Sex steroids and the periosteum--reconsidering the roles of
      androgens and estrogens in periosteal expansion.
AB  - CONTEXT: Traditionally, differences in periosteal bone formation between men and
      women have been assumed to reflect two diverging endocrine effects: stimulatory
      effects of androgens in men and inhibitory effects of estrogens in women. In line
      with this concept, it is tempting to speculate that men experience more
      periosteal bone expansion than women because they are exposed to more endogenous
      androgens and less estradiol. However, recent data challenge this traditional
      concept. EVIDENCE ACQUISITION: A PubMed search was conducted for relevant most
      recent findings in both humans and animals in the context of an intriguing
      observation of ongoing periosteal expansion after estrogen treatment in an
      aromatase-deficient boy. EVIDENCE SYNTHESIS: Human experiments of nature have
      provided evidence that androgens and estrogens are both required for the process
      of pubertal periosteal bone expansion typically associated with the male bone
      phenotype. Androgens alone appear insufficient to drive male periosteal bone
      formation. In both sexes, androgens may stimulate periosteal bone formation, but
      low levels of estrogen may increase the mechanical sensitivity of the periosteum.
      Higher concentrations of endogenous estrogen, however, inhibit periosteal bone
      apposition and/or its interaction with mechanical loading. This biphasic action
      of estrogen on the periosteum may result from a direct effect on its receptor,
      either alpha or beta, but may also depend on changes in serum IGF-I. CONCLUSIONS:
      Simple concepts of the roles of sex steroids in periosteal apposition have to be
      reconsidered in the context of these recent findings.

PMID- 16303834
TI  - The metabolic syndrome is associated with reduced central serotonergic
      responsivity in healthy community volunteers.
AB  - CONTEXT: The pathobiology of the metabolic syndrome remains unclear. The central
      nervous system is likely to be involved via regulation of eating, physical
      activity, blood pressure, and metabolism. OBJECTIVE: The objective of this study
      was to test the hypothesis that low central serotonergic activity is associated
      with the metabolic syndrome. DESIGN, SETTING, PARTICIPANTS: This was a cross
      sectional study of 345 healthy community volunteers, aged 30-55 yr, not taking
      medications for hypertension, lipid disorders, or diabetes. OUTCOME MEASURES:
      Central serotonergic responsivity was assessed with the iv citalopram challenge
      test. The serum prolactin area under the curve (AUC) over 150 min was calculated,
      and all analyses were adjusted for age, sex, plasma citalopram concentration, and
      baseline prolactin. The metabolic syndrome was defined according to the National
      Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF)
      criteria. Insulin resistance was estimated by homeostasis model assessment.
      RESULTS: Compared with other individuals, persons meeting either NCEP or IDF
      criteria for the metabolic syndrome had lower mean prolactin responses (P < 0.05
      for both). Using logistic regression, a decrease in prolactin AUC of 1 sd (-13.6
      ng/ml.h) more than doubled the odds of having the metabolic syndrome (NCEP
      criteria: odds ratio, 2.38; 95% confidence interval, 1.14-4.97; P = 0.02; IDF
      criteria: odds ratio, 2.80; 95% confidence interval, 1.48-5.30; P = 0.002).
      Finally, the prolactin AUC was negatively associated with insulin resistance
      (beta = -0.03, P = 0.02). CONCLUSIONS: Corroborating previous evidence, the
      metabolic syndrome was associated with diminished brain serotonergic activity as
      reflected in a comparative blunting of the prolactin response to a selective
      serotonergic challenge. This association may have implications for the etiology,
      prevention, and treatment of the metabolic syndrome.

PMID- 16303836
TI  - Real-time prognosis for metastatic thyroid carcinoma based on 2-[18F]fluoro-2
      deoxy-D-glucose-positron emission tomography scanning.
AB  - CONTEXT/OBJECTIVE: Approximately 15% of thyroid cancer patients develop
      subsequent metastases. The clinical course of patients with metastatic thyroid
      carcinoma is highly variable. We hypothesized that the metabolic activity of
      metastatic lesions, as defined by retention of 2-[(18)F]fluoro-2-deoxyglucose
      (FDG), would correlate with prognosis. DESIGN/PATIENTS: The initial FDG-positron
      emission tomography (PET) scans from 400 thyroid cancer patients were
      retrospectively reviewed and compared with overall survival (median follow-up,
      7.9 yr). We examined the prognostic value of clinical information such as gender,
      age, serum thyroglobulin, American Joint Committee on Cancer (AJCC) stage,
      histology, radioiodine avidity, FDG-PET positivity, number of FDG-avid lesions,
      and the glycolytic rate of the most active lesion. RESULTS: Age, initial stage,
      histology, thyroglobulin, radioiodine uptake, and PET outcomes all correlated
      with survival by univariate analysis. However, only age and PET results continued
      to be strong predictors of survival under multivariate analysis. The initial
      American Joint Committee on Cancer stage was not a significant predictor of
      survival by multivariate analysis. There were significant inverse relationships
      between survival and both the glycolytic rate of the most active lesion and the
      number of FDG-avid lesions. CONCLUSIONS: FDG-PET scanning is a simple, expensive,
      but powerful means to restage thyroid cancer patients who develop subsequent
      metastases, assigning them to groups that are either at low (FDG negative) or
      high (FDG positive) risk of cancer-associated mortality. We propose that the
      aggressiveness of therapy for metastases should match the FDG-PET status.

PMID- 16303835
TI  - The ectopic adrenocorticotropin syndrome: clinical features, diagnosis,
      management, and long-term follow-up.
AB  - CONTEXT: There are few large series of patients with ectopic, nonpituitary,
      corticotropin (ACTH) secretion (EAS). OBJECTIVE: The objective of this study was
      to analyze the clinical, biochemical, and radiological features, management, and
      treatment outcome of patients with EAS. DESIGN: This was a retrospective case
      record study. SETTING: The setting for this study was a tertiary referral
      hospital center. PATIENTS: Forty patients with EAS were studied. MAIN OUTCOME
      MEASURES: Clinical, biochemical, and radiological features and response to
      therapy and survival were measured. RESULTS: The median follow-up was 5 yr
      (range, 2-30 yr). None of the dynamic tests achieved 100% accuracy, but bilateral
      inferior petrosal sinus sampling showed an absent central gradient in all but one
      case (one of 12). Imaging correctly identified the lesion at first investigation
      in 65% of cases. Bronchial carcinoid tumors were the most common cause of EAS (n
      = 12; 30%), followed by other neuroendocrine tumors (n = 13, 32.5%). In 12.5% of
      patients, the source of EAS was never found. Octreotide scintigraphy and whole
      body venous sampling were of limited value. Surgical attempt at curative
      resection was successful in 83% (10 of 12) of patients with bronchial carcinoid
      tumors; others responded generally well to adrenolytic therapy or bilateral
      adrenalectomy. Tumor histology and the presence of distant metastases were the
      main predictors of overall survival (P < 0.05). CONCLUSIONS: A variety of tests
      and imaging studies are necessary for the correct diagnosis of the EAS, but even
      then, up to 20% of cases present a covert or occult EAS syndrome. These cases
      require a prolonged follow-up, review, and repetition of diagnostic tests and
      scans.

PMID- 16303837
TI  - Novel biomarkers of human growth hormone action from serum proteomic profiling
      using protein chip mass spectrometry.
AB  - CONTEXT: The detection of exogenous human GH (hGH) administration in athletes
      poses unique analytical problems, because its short circulating half-life
      provides only a brief opportunity to detect the administered hormone above
      endogenous levels. Measurement of novel GH-regulated serum protein biomarkers
      might provide an indirect method to detect exogenous GH. OBJECTIVE: The objective
      of this study was to identify new serum biomarkers of GH administration using
      proteomic profiling. DESIGN: Sera from a previously reported, double-blind,
      placebo-controlled GH administration trial were analyzed by protein chip mass
      spectrometry. SETTING: The study was performed at clinical research centers.
      SUBJECTS: Sixty healthy subjects, aged 18-40 yr, who were not elite athletes,
      were studied. INTERVENTIONS: Placebo or recombinant hGH treatment (0.1 or 0.2
      IU/kg.d; 20 subjects/group) was administered for 4 wk, followed by an 8-wk
      washout period. MAIN OUTCOME MEASURES: Protein mass profiles were determined on
      immobilized Cu(2+) chips on d 0 and 21 of GH administration, and multivariate
      analysis was used to classify subjects into GH and placebo administration groups.
      RESULTS: When assessed by cross-validation, the classification performance of
      classifiers based on multivariate analysis of several GH-regulated peaks
      performed no better than classifiers based on the single best peak. This peak, a
      prominent biomarker of 15.1 kDa, was purified and identified as hemoglobin alpha
      chain. The time course of the GH response of this biomarker is similar to that of
      other GH-dependent markers, such as IGF-I. CONCLUSION: This study demonstrates
      that protein mass profiling is an effective tool for the detection of GH
      administration and suggests that measurement of hemoglobin alpha-chain may have
      utility as a novel serum biomarker of GH action.

PMID- 16303838
TI  - Human skeletal muscle lipolysis is more responsive to epinephrine than to
      norepinephrine stimulation in vivo.
AB  - CONTEXT: Triglyceride (TG) deposits in skeletal muscle (SM) are an important
      energy reservoir, and increased im TG content is associated with muscle insulin
      resistance. OBJECTIVE: The objective of the study was to investigate the effect
      of endogenous catecholamines on TG lipolysis in human SM in vivo. Adipose tissue
      (AT) was studied for comparison. DESIGN AND MAIN OUTCOME MEASURES: Glycerol
      levels (index of lipolysis) were measured using microdialysis in the
      gastrocnemius muscle and abdominal sc adipose tissue during a hyperinsulinemic,
      hypoglycemic clamp (n = 13) and in response to in situ perfusion of epinephrine
      and norepinephrine (10(-10) to 10(-5) m) (n = 12). Local tissue blood flow was
      monitored with the ethanol perfusion technique. SETTING: This was an experimental
      study. PARTICIPANTS: The study population consisted of healthy subjects. RESULTS:
      Plasma epinephrine increased 10-fold and plasma norepinephrine 2-fold in response
      to insulin-induced hypoglycemia. In parallel, the fractional glycerol release
      (difference between tissue and arterial glycerol) increased 2-fold in both
      tissues (P < 0.0001). No changes in AT and SM blood flow were registered. When
      the catecholamines were perfused in situ, tissue glycerol increased significantly
      at 10(-7) m of either epinephrine and norepinephrine (P < 0.0001) in AT. The
      maximum stimulation was seen at 10(-6) m norepinephrine (2-fold increase) and 10(
      5) m epinephrine (3-fold increase). In SM, tissue glycerol increased at 10(-7) m
      epinephrine and 10(-6) m norepinephrine, respectively (P < 0.0001); the maximum
      increase of glycerol values (at 10(-6) m) was 2.5 times for epinephrine and 1.6
      times for norepinephrine, respectively (P < 0.01). CONCLUSIONS: The lipolytic
      activity of SM is increased by endogenous catecholamines in vivo and appears to
      be more responsive to epinephrine than norepinephrine stimulation.

PMID- 16303839
TI  - Up-regulation of the gene encoding protein kinase A type I alpha regulatory
      subunit in nodular hyperplasia of parathyroid glands in patients with chronic
      renal failure.
AB  - CONTEXT: Hyperplasia of parathyroid glands in patients with chronic renal failure
      is classified into diffuse (DH) and nodular (NH) types, and NH is often
      refractory to routine medical therapy. OBJECTIVE: Although it is considered that
      the parenchymal cells initially proliferate diffusely and then some of them are
      transformed to form nodules consisting of monoclonal cells, the underlying
      molecular mechanism for such a transformation is not fully understood. In this
      study we tried to identify the genes that are up-regulated in NH. DESIGN AND
      SETTING: The cDNA population prepared from DH was subtracted from that prepared
      from NH by a PCR-based cDNA subtraction method. The resultant cDNAs were cloned
      and sequenced. To confirm the up-regulation of the identified genes, a total of
      35 parathyroid glands (18 DH, 16 NH, and one mixed) obtained from 21 patients
      were analyzed. RESULTS: One of the nuclear genes identified was the PRKAR1A gene,
      which encodes type Ialpha regulatory subunit (RIalpha) of cAMP-dependent protein
      kinase (PKA). Immunohistochemical analysis demonstrated that RIalpha was
      abundantly expressed in the nodular region, whereas the adjacent diffuse region
      displayed relatively low expression. Northern and Western blot analyses
      demonstrated up-regulation of RIalpha expression in most NH tested. Determination
      of PKA activities revealed that free PKA activities measured in the absence of
      cAMP in the assay were inversely correlated with RIalpha expression, indicating
      the functional significance of RIalpha up-regulation. CONCLUSIONS: These results
      suggest that the aberrant expression of RIalpha is involved in the diffuse to
      nodular transformation of hyperplasia of parathyroid glands by impairing cAMP/PKA
      signal transduction.

PMID- 16303840
TI  - Estrogen-metabolizing enzymes in breast cancers from women over the age of 80
      years.
AB  - CONTEXT: Aromatase, steroid sulfatase, and 17beta-hydroxysteroid dehydrogenase
      type 1 (HSD-1) peripherally up-regulate, whereas estrogen sulfotransferase (EST)
      and HSD-2 down-regulate, the synthesis of active and more potent estrogens. These
      estrogen-metabolizing enzymes (EMEs) are important in postmenopausal breast
      cancers, but have never been systematically examined in breast cancers of the
      elderly. OBJECTIVE AND DESIGN: mRNA levels of EMEs in cancerous and normal breast
      tissues from 39 elderly patients (age, 80-99 yr) were compared with those from 39
      controls (age, 37-70 yr) or compared according to estrogen (ER)/progesterone (PR)
      receptor status. RESULTS: Aromatase levels were higher in cancers of the elderly
      (EldCa) than in normal tissue of the elderly (P = 0.0008) or cancers of controls
      (P = 0.0033). In contrast, levels of steroid sulfatase and EST were higher in
      cancers of controls than normal tissue of controls (P = 0.0046 and P < 0.0001,
      respectively) or EldCa (P = 0.0001 and P < 0.0001, respectively). Levels of HSD-1
      and HSD-2 did not differ significantly between any two of the categories. Among
      EldCa, HSD-1 levels were higher in ER/PR-positive than in ER/PR-negative
      carcinomas, whereas EST and HSD-2 exhibited opposite results. CONCLUSIONS: The
      importance of aromatase is relatively increased in EldCa. ER/PR-positive EldCa
      exhibited a pattern of EMEs more beneficial to the production of estrogen than
      did ER/PR-negative EldCa. The specific pattern exhibited in EldCa may elucidate
      the role of EMEs in the absence of ovarian estrogens in the pathogenesis of
      breast cancer.

PMID- 16303841
TI  - Interferon-gamma-inducible alpha-chemokine CXCL10 involvement in Graves'
      ophthalmopathy: modulation by peroxisome proliferator-activated receptor-gamma
      agonists.
AB  - CONTEXT: CXC alpha-chemokine CXCL10/inducing protein-10 play an important role in
      the initial phases of autoimmune thyroid disorders. Human thyrocytes in primary
      culture produce large amounts of CXCL10 when stimulated by interferon-gamma
      (IFNgamma) and TNFalpha. OBJECTIVE: Serum CXCL10 levels (sCXCL10) were measured
      in patients with active or inactive Graves' ophthalmopathy (GO). The effects of
      IFNgamma and TNFalpha stimulation and peroxisome proliferator-activated receptor
      gamma (PPARgamma) activation on CXCL10 secretion in primary cultures of
      thyrocytes, orbital fibroblasts, and preadipocytes were tested. PATIENTS: Sixty
      consecutive patients with Graves' disease, 60 age- and sex-matched patients with
      GO, and 60 controls were studied. RESULTS: sCXCL10 was higher (P < 0.0001) in
      Graves' disease (120 +/- 83 pg/ml; n = 60) and GO (122 +/- 71; n = 60) patients
      than in age- and sex-matched euthyroid controls (72 +/- 32; n = 60). Among GO
      patients, sCXCL10 levels were significantly higher in those (n = 14) with active
      disease (171 +/- 197) than in those with inactive disease (114 +/- 45 pg/ml; P <
      0.003). In primary cultures of thyrocytes, retrobulbar fibroblasts and
      retrobulbar preadipocytes from GO patients, CXCL10 production was absent under
      basal conditions; dose-dependent secretion of CXCL10 was not induced by TNFalpha
      alone, whereas stimulation with IFNgamma or TNFalpha plus IFNgamma induced CXCL10
      release. Treatment of all cell types with the PPARgamma agonist, rosiglitazone,
      dose-dependently (0.1-10 microm) suppressed IFNgamma- plus TNFalpha-induced
      CXCL10 release. CONCLUSIONS: We conclude that in GO, thyrocytes and retrobulbar
      cell types participate in the self-perpetuation of inflammation by releasing
      chemokines under the influence of cytokines. PPARgamma activation plays an
      inhibitory role in this process.

PMID- 16303842
TI  - Intellectual and motor development of young adults with congenital hypothyroidism
      diagnosed by neonatal screening.
AB  - CONTEXT: Long-term follow-up data on cognitive and motor functioning in adult
      patients with congenital hypothyroidism, diagnosed by neonatal screening, are
      scarce. Hence, it is still unclear whether the frequently reported cognitive and
      motor deficits observed during childhood persist in adulthood. OBJECTIVE: The
      objective of this study was to examine cognitive and motor functioning in young
      adults with congenital hypothyroidism, born in the first 2 yr after the
      introduction of the Dutch neonatal screening program. DESIGN/SETTING/PATIENTS:
      Seventy patients were tested (mean age, 21.5 yr); 49 of them were previously
      tested at 9.5 yr. The median age at the start of treatment was 28 d (range, 4-293
      d). Congenital hypothyroidism was classified as severe, moderate, or mild,
      according to pretreatment T(4) concentrations. MAIN OUTCOME MEASUREMENT: The main
      outcome measurement was the influence of the severity of congenital
      hypothyroidism and age at which T(4) supplementation was started on cognitive and
      motor outcome. RESULTS: Patients, particularly those with severe congenital
      hypothyroidism, had significantly higher (i.e. worse) motor scores (total score,
      7.8; ball skills, 2.0; balance, 4.1) compared with controls (total score, 3.2;
      ball skills, 0.7; balance, 1.1), and lower full-scale (95.8), verbal (96.4), and
      performance (95.6) intelligence quotient (IQ) scores than the normal population.
      No significant change in IQ from childhood to adulthood was found, and for the
      majority of patients, motor score classification remained the same. The severity
      of congenital hypothyroidism, but not the starting day of treatment, was
      correlated with IQ and motor scores. CONCLUSIONS: It is concluded that the
      severity of congenital hypothyroidism, but not the timing of treatment
      initiation, is an important factor determining long-term cognitive and motor
      outcome. Clearly, detrimental effects on developmental outcome in patients with
      congenital hypothyroidism persist over time.

PMID- 16303843
TI  - 25-hydroxyvitamin D deficiency in renal transplant recipients.
AB  - CONTEXT: Bone disease after kidney transplantation is a common problem. The serum
      levels of the active vitamin D metabolite 1,25-dihydroxyvitamin D(3)
      [1,25(OH)(2)D] have been studied extensively. In contrast, there has not been
      much concern about the serum levels of 25-hydroxyvitamin D(3) [25(OH)D]. However,
      it is well recognized that serum levels of 1,25(OH)(2)D are often normal in
      vitamin D-deficient patients. Moreover, inadequate serum 25(OH)D may limit the
      extrarenal production of 1,25(OH)(2)D that could lead to increased risk of many
      chronic diseases. OBJECTIVE: We analyzed whether renal transplant patients were
      at a higher risk of 25(OH)D deficiency because of the consequence of their need
      to protect themselves from sun exposure. DESIGN, SETTING, AND PATIENTS: We
      hypothesized that renal transplant recipients are at high risk to develop 25(OH)D
      deficiency. Serum 25(OH)D levels were analyzed in renal transplant patients with
      adequate renal function and in an age- and gender-matched control group (n = 31)
      at the end of winter. All renal transplant patients practiced solar UV-protection
      after transplantation. 25(OH)D levels were compared using a nonparametrical test
      (Wilcoxon rank sum test). RESULTS: Serum 25(OH)D levels were significantly lower
      in renal transplant patients compared with controls (P = 0.007). Geometric mean
      (with 95% confidence interval) in renal transplant patients was 10.9 ng/ml (8.2
      14.3) compared with 20.0 ng/ml (15.7-25.5) in the control group. CONCLUSIONS:
      Renal transplant recipients are at high risk to develop 25(OH)D deficiency.
      Treatment with vitamin D is recommended to correct their vitamin D deficiency,
      which may help protect them from serious vitamin D deficiency-related health
      problems that include an increased risk for internal malignancies.

PMID- 16303844
TI  - Lipid metabolism and adipokine levels in fatty acid-binding protein null and
      transgenic mice.
AB  - Fatty acid-binding proteins (FABPs) facilitate the diffusion of fatty acids
      within cellular cytoplasm. Compared with C57Bl/6J mice maintained on a high-fat
      diet, adipose-FABP (A-FABP) null mice exhibit increased fat mass, decreased
      lipolysis, increased muscle glucose oxidation, and attenuated insulin resistance,
      whereas overexpression of epithelial-FABP (E-FABP) in adipose tissue results in
      decreased fat mass, increased lipolysis, and potentiated insulin resistance. To
      identify the mechanisms that underlie these processes, real-time PCR analyses
      indicate that the expression of hormone-sensitive lipase is reduced, while
      perilipin A is increased in A-FABP/aP2 null mice relative to E-FABP
      overexpressing mice. In contrast, de novo lipogenesis and expression of genes
      encoding lipoprotein lipase, CD36, long-chain acyl-CoA synthetase 5, and
      diacylglycerol acyltransferase are increased in A-FABP/aP2 null mice relative to
      E-FABP transgenic animals. Consistent with an increase in de novo lipogenesis,
      there was an increase in adipose C16:0 and C16:1 acyl-CoA pools. There were no
      changes in serum free fatty acids between genotypes. Serum levels of resistin
      were decreased in the E-FABP transgenic mice, whereas serum and tissue
      adiponectin were increased in A-FABP/aP2 null mice and decreased in E-FABP
      transgenic animals; leptin expression was unaffected. These results suggest that
      the balance between lipolysis and lipogenesis in adipocytes is remodeled in the
      FABP null and transgenic mice and is accompanied by the reprogramming of
      adipokine expression in fat cells and overall changes in plasma adipokines.

PMID- 16303845
TI  - Increased adrenal androgen secretion with inhibition of 11beta-hydroxylase in HIV
      infected women.
AB  - Adrenal androgen production is reduced in association with disease severity in
      HIV-infected women. This response may be maladaptive in terms of maintenance of
      lean body mass, functional status, and immune function. The aim of this study was
      to assess whether the use of an adrenal enzyme inhibitor of 11beta-hydroxylase
      might increase androgen production in this population. We conducted a randomized,
      double-blind, placebo-controlled study of metyrapone (500 mg p.o. qid) or placebo
      for 2 wk in 10 HIV-infected women with AIDS wasting [weight <90% ideal body
      weight (IBW) or weight loss >10%] and reduced androgen levels. Basal and ACTH
      stimulated androgen, mineralocorticoid, and glucocorticoid levels were measured
      at baseline and after 14 days of treatment. Subjects were similar in age (40.9 +/
      0.9 yr), weight (91.7 +/- 3.5% IBW) and hormone concentrations at study entry.
      Total testosterone (84 +/- 54 vs. -0.4 +/- 2 ng/dl, P = 0.024), free testosterone
      (6.5 +/- 2.8 vs. 0.1 +/- 0.1 pg/ml, P = 0.024), DHEA (5.0 +/- 3.2 vs. -0.6 +/-
      0.5 microg/l, P = 0.024), and 11-deoxycortisol (2,145 +/- 820 vs. -14 +/- 22
      ng/dl, P = 0.024) levels increased in response to metyrapone compared with
      placebo treatment. In response to ACTH, significant increases in the
      DHEA/cortisol ratio (174 +/- 48 vs. 3 +/- 3, P = 0.008) were seen in the
      metyrapone group compared with placebo. Blood pressure and electrolytes did not
      change, and signs of adrenal insufficiency were not apparent. These data
      demonstrate that inhibition of 11beta-hydroxylase with metyrapone increases
      adrenal androgen secretion in HIV-infected women. Further studies are needed to
      assess the physiological effects of this strategy to increase anabolic hormone
      levels in severe stress, including detailed testing to rule out the potential
      risk of concomitant adrenal insufficiency.

PMID- 16303846
TI  - Small rat islets are superior to large islets in in vitro function and in
      transplantation outcomes.
AB  - Barriers to the use of islet transplantation as a practical treatment for
      diabetes include the limited number of available donor pancreata. This project
      was designed to determine whether the size of the islet could influence the
      success rate of islet transplantations in rats. Islets from adult rats were
      divided into two groups containing small (diameter <125 microm) or large
      (diameter >150 microm) islets. An average pancreas yielded three times more small
      islets than large. Smaller islets were approximately 20% more viable, with large
      islets containing a scattered pattern of necrotic and apoptotic cells or central
      core cell death. Small islets in culture consumed twice as much oxygen as large
      islets when normalized for the same islet equivalents. In static incubation,
      small islets released three times more insulin under basal conditions than did
      large islets. During exposure to high glucose conditions, the small islets
      released four times more insulin than the same islet equivalencies of large
      islets, and five times more insulin was released by the small islets in response
      to glucose and depolarization with K+. Most importantly, the small islets were
      far superior to large islets when transplanted into diabetic animals. When
      marginal islet equivalencies were used for renal subcapsular transplantation,
      large islets failed to produce euglycemia in any recipient rats, whereas small
      islets were successful 80% of the time. The results indicate that small islets
      are superior to large islets in in vitro testing and for transplantation into the
      kidney capsule of diabetic rats.

PMID- 16303847
TI  - Hyper-adhesion in desmosomes: its regulation in wound healing and possible
      relationship to cadherin crystal structure.
AB  - The resistance of tissues to physical stress is dependent upon strong cell-cell
      adhesion in which desmosomes play a crucial role. We propose that desmosomes
      fulfil this function by adopting a more strongly adhesive state, hyper-adhesion,
      than other junctions. We show that the hyper-adhesive desmosomes in epidermis
      resist disruption by ethylene glycol bis(2-aminoethyl ether)-N,N,N'N'-tetraacetic
      acid (EGTA) and are thus independent of Ca2+. We propose that Ca2+ independence
      is the normal condition for tissue desmosomes. Ca2+ independence is associated
      with an organised arrangement of the intercellular adhesive material exemplified
      by a dense midline. When epidermis is wounded, desmosomes in the wound-edge
      epithelium lose hyper-adhesiveness and become Ca2+ dependent, i.e. readily
      dissociated by EGTA. Ca2+-dependent desmosomes lack a midline and show narrowing
      of the intercellular space. We suggest that this indicates a less-organised,
      weakly adhesive arrangement of the desmosomal cadherins, resembling classical
      cadherins in adherens junctions. Transition to Ca2+ dependence on wounding is
      accompanied by relocalisation of protein kinase C alpha to desmosomal plaques
      suggesting that an 'inside-out' transmembrane signal is responsible for changing
      desmosomal adhesiveness. We model hyper-adhesive desmosomes using the crystal
      packing observed for the ectodomain of C-cadherin and show how the regularity of
      this 3D array provides a possible explanation for Ca2+ independence.

PMID- 16303848
TI  - A role for the fission yeast Rqh1 helicase in chromosome segregation.
AB  - Schizosaccharomyces pombe Rqh1 protein is a member of the RecQ DNA helicase
      family. Members of this protein family are mutated in several human genome
      instability syndromes, including Bloom, Werner and Rothmund-Thomson syndromes.
      RecQ helicases participate in recombination repair of stalled replication forks
      or DNA breaks, but the precise mechanisms that lead to the development of cancer
      in these diseases have remained obscure. Here, we reveal a function for Rqh1 in
      chromosome segregation even in the absence of exogenous insult to the DNA. We
      show that cells lacking Rqh1 are delayed in anaphase progression, and show
      lagging chromosomal DNA, which is particularly apparent in the rDNA locus. This
      mitotic delay is dependent on the spindle checkpoint, as deletion of mad2
      abolishes the delay as well as the accumulation of Cut2 in rqh1delta cells.
      Furthermore, relieving replication fork arrest in the rDNA repeat by deletion of
      reb1+ partially suppresses rqh1delta phenotypes. These data are consistent with
      the function of the Top3-RecQ complex in maintenance of the rDNA structure by
      processing aberrant chromosome structures arising from DNA replication. The
      chromosome segregation defects seen in the absence of functional RecQ helicases
      may contribute to the pathogenesis of human RecQ helicase disorders.

PMID- 16303849
TI  - Histone H2AZ dimerizes with a novel variant H2B and is enriched at repetitive DNA
      in Trypanosoma brucei.
AB  - H2AZ is a widely conserved histone variant that is implicated in protecting
      euchromatin from the spread of heterochromatin. H2AZ is incorporated into
      nucleosomes as a heterodimer with H2B, by the SWR1 ATP-dependent chromatin
      remodeling complex. We have identified a homolog of H2AZ in the protozoan
      parasite Trypanosoma brucei, along with a novel variant of histone H2B (H2BV)
      that shares approximately 38% sequence identity with major H2B. Both H2AZ and
      H2BV are essential for viability. H2AZ localizes within the nucleus in a pattern
      that is distinct from canonical H2A and is largely absent from sites of
      transcription visualized by incorporation of 5-bromo-UTP (BrUTP). H2AZ and H2BV
      colocalize throughout the cell cycle and exhibit nearly identical genomic
      distribution patterns, as assessed by chromatin immunoprecipitation. H2AZ co
      immunoprecipitates with H2BV but not with histones H2B or H2A nor with the
      variant H3V. These data strongly suggest that H2AZ and H2BV function together
      within a single nucleosome, marking the first time an H2AZ has been shown to
      associate with a non-canonical histone H2B.

PMID- 16303850
TI  - Involvement of aquaporin-4 in astroglial cell migration and glial scar formation.
AB  - Aquaporin-4, the major water-selective channel in astroglia throughout the
      central nervous system, facilitates water movement into and out of the brain.
      Here, we identify a novel role for aquaporin-4 in astroglial cell migration, as
      occurs during glial scar formation. Astroglia cultured from the neocortex of
      aquaporin-4-null mice had similar morphology, proliferation and adhesion, but
      markedly impaired migration determined by Transwell migration efficiency (18+/-2
      vs 58+/-4% of cells migrated towards 10% serum in 8 hours; P<0.001) and wound
      healing rate (4.6 vs 7.0 microm/hour speed of wound edge; P<0.001) compared with
      wild-type mice. Transwell migration was similarly impaired (25+/-4% migrated
      cells) in wild-type astroglia after approximately 90% reduction in aquaporin-4
      protein expression by RNA inhibition. Aquaporin-4 was polarized to the leading
      edge of the plasma membrane in migrating wild-type astroglia, where rapid shape
      changes were seen by video microscopy. Astroglial cell migration was enhanced by
      a small extracellular osmotic gradient, suggesting that aquaporin-4 facilitates
      water influx across the leading edge of a migrating cell. In an in vivo model of
      reactive gliosis and astroglial cell migration produced by cortical stab injury,
      glial scar formation was remarkably impaired in aquaporin-4-null mice, with
      reduced migration of reactive astroglia towards the site of injury. Our findings
      provide evidence for the involvement of aquaporin-4 in astroglial cell migration,
      which occurs during glial scar formation in brain injury, stroke, tumor and focal
      abscess.

PMID- 16303851
TI  - Neurite outgrowth involves adenomatous polyposis coli protein and beta-catenin.
AB  - Neuronal morphogenesis involves the initial formation of neurites and then
      differentiation of neurites into axons and dendrites. The mechanisms underlying
      neurite formation are poorly understood. A candidate protein for controlling
      neurite extension is the adenomatous polyposis coli (APC) protein, which
      regulates membrane extensions, microtubules and beta-catenin-mediated
      transcription downstream of Wnt signaling. APC is enriched at the tip of several
      neurites of unpolarized hippocampal neurons and the tip of only the long axon in
      polarized hippocampal neurons. Significantly, APC localized to the tip of only
      one neurite, marked by dephospho-tau as the future axon, before that neurite had
      grown considerably longer than other neurites. To determine whether neurite
      outgrowth was affected by beta-catenin accumulation and signaling, a stabilized
      beta-catenin mutant was expressed in PC12 cells, and neurite formation was
      measured. Stabilized beta-catenin mutants accumulated in APC clusters and
      inhibited neurite formation and growth. Importantly, these effects were also
      observed was independently of the gene transcriptional activity of beta-catenin.
      These results indicate that APC is involved in both early neurite outgrowth and
      increased growth of the future axon, and that beta-catenin has a structural role
      in inhibiting APC function in neurite growth.

PMID- 16303852
TI  - The Caenorhabditis elegans GATA factor elt-1 is essential for differentiation and
      maintenance of hypodermal seam cells and for normal locomotion.
AB  - The Caenorhabditis elegans GATA transcription factor elt-1 has previously been
      shown to have a central role in the specification of hypodermal (epidermal) cell
      fates and acts several cell divisions before the birth of hypodermal cells. Here
      we report that elt-1 also has essential functions during subsequent development.
      Reporter gene studies show that elt-1 expression is maintained in lateral seam
      cells throughout development and elt-1 RNA interference experiments support an
      essential role for elt-1 in the differentiation of lateral seam cells in the
      embryo. The maintenance of seam-cell fates in all larval stages including L2d and
      dauer also requires elt-1. The elt-1 RNAi phenotype shows that seam cells are
      essential for the structural integrity of adult hermaphrodites in the vulval
      region and for diametric shrinkage during dauer larval formation. By contrast,
      severe seam-cell loss in the larval stages has little effect on moulting,
      indicating that the presence of these cells is not essential for this process.
      The elt-1 reporter gene is also expressed in neurones of the locomotory circuit.
      Loss of elt-1 function during postembryonic development results in a
      hypermotility phenotype whereas overexpression of elt-1 leads to a reciprocal
      phenotype of reduced motility and paralysis. These results suggest that elt-1 is
      a key regulator of neuronal function in larvae and adult worms.

PMID- 16303853
TI  - Bax activation and translocation to mitochondria mediate EGF-induced programmed
      cell death.
AB  - The ErbB family of receptor tyrosine kinases is involved in the regulation of
      cell proliferation, differentiation and apoptosis. Previous studies indicate that
      cells expressing elevated levels of the EGFR and ErbB-2 undergo programmed cell
      death in response to EGF or other EGFR ligands. However, the detailed mechanisms
      of EGF-induced apoptosis are unclear. This report demonstrates that in the cells
      undergoing EGF-dependent apoptosis Bax changes its conformation and forms
      multimeric aggregates, which accumulate on the mitochondrial membrane. Bax
      activation and translocation to the mitochondria induces a loss of mitochondrial
      transmembrane potential and cell death. Also, during EGF-induced apoptosis there
      is downregulation of Bcl-xL, an anti-apoptotic protein. Expression of Bcl-xL in
      cells susceptible to EGF-dependent apoptosis prevents cell death. The data
      indicate that addition of EGF does not result in a significant release of
      cytochrome c from mitochondria and EGF-induced apoptosis is mainly caspase
      independent.

PMID- 16303854
TI  - Mitochondrial reactive oxygen species contribute to high NaCl-induced activation
      of the transcription factor TonEBP/OREBP.
AB  - Hypertonicity activates the transcription factor tonicity-responsive
      enhancer/osmotic response element binding protein (TonEBP/OREBP), resulting in
      increased expression of genes involved in osmoprotective accumulation of organic
      osmolytes, including glycine betaine, and in increased expression of
      osmoprotective heat shock proteins. Our previous studies showed that high NaCl
      increases reactive oxygen species (ROS), which contribute to activation of
      TonEBP/OREBP. Mitochondria are a major source of ROS. The purpose of the present
      study was to examine whether mitochondria produce the ROS that contribute to
      activation of TonEBP/OREBP. We inhibited mitochondrial ROS production in HEK293
      cells with rotenone and myxothiazol, which inhibit mitochondrial complexes I and
      III, respectively. Rotenone (250 nM) and myxothiazol (12 nM) reduce high NaCl
      induced ROS over 40%, whereas apocynin (100 microM), an inhibitor of NADPH
      oxidase, and allopurinol (100 microM), an inhibitor of xanthine oxidase, have no
      significant effect. Rotenone and myxothiazol reduce high NaCl-induced increases
      in TonEBP/OREBP transcriptional activity (ORE/TonE reporter assay) and BGT1
      (betaine transporter) mRNA abundance ranging from 53 to 69%. They inhibit high
      NaCl-induced TonEBP/OREBP transactivating activity, but not its nuclear
      translocation. Release of ATP into the medium on hypertonic stress has been
      proposed to be a signal that triggers cellular osmotic responses. However, we do
      not detect release of ATP into the medium or inhibition of high NaCl-induced
      ORE/TonE reporter activity by an ATPase, apyrase (20 U/ml), indicating that high
      NaCl-induced activation of TonEBP/OREBP is not mediated by release of ATP. We
      conclude that high NaCl increases mitochondrial ROS production, which contributes
      to the activation of TonEBP/OREBP by increasing its transactivating activity.

PMID- 16303855
TI  - Identification and localization of TRPC channels in the rat kidney.
AB  - It is well established that transient receptor potential (TRP) channels are
      activated following stimulation of G protein-coupled membrane receptors linked to
      PLC, but their differential expression in various cells of the renal nephron has
      not been described. In the present study, immunoprecipitations from rat kidney
      lysates followed by Western blot analysis using TRPC-specific, affinity-purified
      antibodies revealed the presence of TRPC1, -C3, and -C6. TRPC4, -C5, and -C7 were
      nondetectable. TRPC1 immunofluorescence was detected in glomeruli and specific
      tubular cells of the cortex and outer medulla. TRPC1 colocalized with aquaporin
      1, a marker for proximal tubule and thin descending limb, but not with aquaporin
      2, a marker for connecting tubule and collecting duct cells. TRPC3 and -C6
      immunolabeling was predominantly confined to glomeruli and specific tubular cells
      of the cortex and both the outer and inner medulla. TRPC3 and -C6 colocalized
      with aquaporin-2, but not with the Na(+)/Ca(2+) exchanger or peanut lectin. Thus
      TRPC3 and -C6 proteins are expressed in principle cells of the collecting duct.
      In polarized cultures of M1 and IMCD-3 collecting duct cells, TRPC3 was localized
      exclusively to the apical domain, whereas TRPC6 was found in both the basolateral
      and apical membranes. TRPC3 and TRPC6 were also detected in primary podocyte
      cultures, whereas TRPC1 was exclusively expressed in mesangial cell cultures.
      Specific immunopositive labeling for TRPC4, -C5, or -C7 was not observed in
      kidney sections or cell lines. These results suggest that TRPC1, -C3, and -C6 may
      play a functional role in PLC-dependent signaling in specific regions of the
      nephron.

PMID- 16303856
TI  - Adipocytes support cAMP-dependent translocation of aquaporin-2 from intracellular
      sites distinct from the insulin-responsive GLUT4 storage compartment.
AB  - Aquaporin-2 (AQP2), when expressed in fully differentiated 3T3-L1 adipocytes,
      displays cAMP-dependent plasma membrane translocation in a manner similar to its
      behavior in renal epithelial cells. The translocation of AQP2 required
      phosphorylation at serine 256, as the expression of AQP2/S256D was constitutively
      plasma membrane localized, whereas AQP2/S256A was refractory to forskolin
      stimulation. Unlike GLUT4, this property is not inhibited by depolymerization of
      cortical actin. In addition, coexpression with the dominant negative form of TC10
      (TC10/T31N) or inhibition of phosphatidylinositol 3-kinase did not abrogate the
      cAMP-mediated response. Under basal conditions, AQP2 is localized in both the
      perinuclear region and in punctate vesicles scattered within the periphery of the
      cell. Two- and three-dimensional confocal immunofluorescence microscopy
      demonstrated that the adipocyte AQP2 cAMP-responsive compartment was distinct
      from the GLUT4 insulin-responsive compartment. Consistent with this conclusion,
      insulin was an effective stimulator of GLUT4 translocation but had no effect on
      AQP2. Conversely, forskolin induced AQP2 translocation but not GLUT4.
      Colocalization studies with the early endosomal marker EEA1 and transferrin
      receptor suggested that the AQP2 compartment is mostly distinct from endosomal
      vesicles. Interestingly, however, the peripheral AQP2 vesicles significantly
      overlapped vesicle-associated membrane protein-2, underscoring the role of the
      latter in hormone-regulated exocytosis. To acquire insulin responsiveness
      following biosynthesis, GLUT4 undergoes a slow sorting step that requires 6-9 h.
      In contrast, AQP2 rapidly acquires forskolin responsiveness (3 h following
      biosynthesis) and directly enters the cAMP-regulated compartment without
      transiting the plasma membrane. Together, these data demonstrate that adipocytes
      display two different intracellular sorting mechanisms that direct distinct
      hormone-sensitive partitioning of GLUT4 and AQP2.

PMID- 16303857
TI  - Adenosine as a mediator of macula densa-dependent inhibition of renin secretion.
AB  - Adenosine acting through A(1) adenosine receptors (A1AR) has been shown
      previously to be required for the vasoconstriction elicited by high luminal NaCl
      concentrations at the macula densa (MD). The present experiments were performed
      to investigate a possible role of A1AR in MD control of renin secretion in
      conscious wild-type (WT) and A1AR-deficient mice. The intravenous injection of
      NaCl (5% body wt) reduced plasma renin concentration (PRC; ng ANG I x ml(-1) x h(
      1)) from 1,479 +/- 129 to 711 +/- 77 (P < 0.0001; n = 18) in WT mice but did not
      significantly change PRC in A1AR-/- mice (1,352 +/- 168 during control vs. 1,744
      +/- 294 following NaCl; P = 0.19; n = 17). NaCl injections also caused a
      significant reduction in PRC in beta(1)/beta(2)-adrenergic receptor-/- mice (298
      +/- 47 vs. 183 +/- 42; P = 0.03; n = 6). Injections of isotonic NaHCO(3) (5% body
      wt) elicited significant increases in PRC in both WT and A1AR-/- mice. NaCl as
      well as NaHCO(3) injections were accompanied by transient increases in blood
      pressure, heart rate, and activity that were similar in WT and A1AR-/- mice. The
      increase in PRC caused by an intraperitoneal injection of furosemide (40 mg/kg)
      was comparable in WT and A1AR-/- mice, and it was accompanied by similar
      transient increases in blood pressure, heart rate, and activity. Similarly, the
      stimulation of PRC caused by hydralazine was the same in WT and A1AR-/- mice. We
      conclude that the inhibition of renin secretion in response to an increase in
      NaCl at the MD requires A1AR and therefore appears to be adenosine dependent,
      whereas the stimulation of renin secretion during reductions in MD NaCl transport
      or arterial pressure does not require functional A1AR.

PMID- 16303858
TI  - Identification of a QTL on chromosome 1 for impaired autoregulation of RBF in
      fawn-hooded hypertensive rats.
AB  - The present study evaluated whether the impairment in autoregulation of renal
      blood flow (RBF) in the fawn-hooded Hypertensive (FHH) rat colocalizes with the
      Rf-1 region on chromosome 1 that has been previously linked to the development of
      proteinuria in this strain. Autoregulation of RBF was measured in FHH and a
      consomic strain (FHH.1(BN)) in which chromosome 1 from the Brown-Norway (BN) rat
      was introgressed into the FHH genetic background. The autoregulation indexes (AI)
      averaged 0.80 +/- 0.08 in the FHH and 0.19 +/- 0.05 in the FHH.1(BN) rats. We
      next performed a genetic linkage analysis for autoregulation of RBF in 85 F2 rats
      generated from a backcross of FHH.1(BN) consomic and FHH rats. The results
      revealed a significant quantitative trait locus (QTL) with a peak logarithm of
      the odds score of 6.3 near marker D1Rat376. To confirm the existence of this QTL,
      five overlapping congenic strains were created that spanned the region from
      markers D1Rat234 to D1Mit14. Transfer of a region of BN chromosome 1 from markers
      D1Mgh13 to D1Rat89 into the FHH genetic background improved autoregulation of RBF
      (AI = 0.23 +/- 0.04) and reduced protein excretion. In contrast, RBF was poorly
      autoregulated and the rats were not protected from proteinuria in congenic
      strains in which other regions of chromosome 1 that exclude the D1Rat376 marker
      were transferred. These results indicate that there is a gene(s) that influences
      autoregulation of RBF and proteinuria between markers D1Mgh13 and D1Rat89 on
      chromosome 1 that lies within the confidence interval of the Rf-1 QTL previously
      linked to the development of proteinuria in FHH rats.

PMID- 16303859
TI  - Regulation of blood pressure, the epithelial sodium channel (ENaC), and other key
      renal sodium transporters by chronic insulin infusion in rats.
AB  - Hyperinsulinemia is associated with hypertension. Dysregulation of renal distal
      tubule sodium reabsorption may play a role. We evaluated the regulation of the
      epithelial sodium channel (ENaC) and the thiazide-sensitive Na-Cl cotransporter
      (NCC) during chronic hyperinsulinemia in rats and correlated these changes to
      blood pressure as determined by radiotelemetry. Male Sprague-Dawley rats (
      approximately 270 g) underwent one of the following three treatments for 4 wk (n
      = 6/group): 1) control; 2) insulin-infused plus 20% dextrose in drinking water;
      or 3) glucose water-drinking (20% dextrose in water). Mean arterial pressures
      were increased by insulin and glucose (mmHg at 3 wk): 98 +/- 1 (control), 107 +/-
      2 (insulin), and 109 +/- 3 (glucose), P < 0.01. Insulin (but not glucose)
      increased natriuretic response to benzamil (ENaC inhibitor) and
      hydrochlorothiazide (NCC inhibitor) on average by 125 and 60%, respectively,
      relative to control rats, suggesting increased activity of these reabsorptive
      pathways. Neither insulin nor glucose affected the renal protein abundances of
      NCC or the ENaC subunits (alpha, beta, and gamma) in kidney cortex, outer
      medulla, or inner medulla in a major way, as determined by immunoblotting.
      However, insulin and to some extent glucose increased apical localization of
      these subunits in cortical collecting duct principal cells, as determined by
      immunoperoxidase labeling. In addition, insulin decreased cortical "with no
      lysine" kinase (WNK4) abundance (by 16% relative to control), which may have
      increased NCC activity. Overall, insulin infusion increased blood pressure, and
      NCC and ENaC activity in rats. Increased apical targeting of ENaC and decreased
      WNK4 expression may be involved.

PMID- 16303860
TI  - Systemic chemotherapy in inoperable or metastatic bladder cancer.
AB  - Urothelial cancer is a common malignancy. The management of patients with
      recurrent disease after cystectomy or initially metastatic or unresectable
      disease represents a therapeutic challenge. Systemic chemotherapy prolongs
      survival but long-term survival remains infrequent. During recent years there has
      been improvement due to the use of novel chemotherapeutic agents, mainly
      gemcitabine and the taxanes. The long-considered-standard MVAC has been
      challenged by combinations showing more favourable toxicity profiles and equal
      (gemcitabine-cisplatin) or even improved (dose-dense, G-CSF-supported MVAC)
      efficacy. Specific interest has also been generated in specific groups of
      patients (elderly patients, patients with renal function impairment or
      comorbidities), who are not fit for the standard cisplatin-based chemotherapy but
      can derive significant benefit from carboplatin- or taxane-based treatment.
      Retrospective analyses have enabled the identification of groups of patients with
      different prognoses, who possibly require different therapeutic approaches.
      Modern chemotherapy offers a chance of long-term survival in patients without
      visceral metastases, possibly in combination with definitive local treatment.
      Finally, the progress of targeted therapies in other neoplasms seems to be
      reflected in advanced bladder cancer by recent studies indicating that biological
      agents can be combined with modern chemotherapy. The true role of such therapies
      is currently being evaluated.

PMID- 16303861
TI  - Cetuximab and irinotecan/5-fluorouracil/folinic acid is a safe combination for
      the first-line treatment of patients with epidermal growth factor receptor
      expressing metastatic colorectal carcinoma.
AB  - BACKGROUND: To investigate the safety/tolerability of the EGFR-antibody cetuximab
      when added to irinotecan/5-fluorouracil (5-FU)/folinic acid (FA) for first-line
      treatment in patients with metastatic colorectal cancer (mCRC). PATIENTS AND
      METHODS: Twenty-one patients with untreated, metastatic, EGFR-expressing CRC
      received cetuximab 400 mg/m(2) as an initial dose, and thereafter 250 mg/m(2)
      weekly. In addition, patients received infusional 5-FU (24 h) in two dose levels
      (1500 mg/m(2), low 5-FU group, n = 6 or 2000 mg/m(2), high 5-FU group, n = 15),
      plus FA at 500 mg/m(2) and irinotecan at 80 mg/m(2), weekly x6 q50d. RESULTS:
      Twenty patients were assessable for tolerability after the first cycle. There
      were no dose limiting toxicities (DLTs) in the low 5-FU group and three DLTs
      (20%) in the high 5-FU group (two patients with diarrhea grade 3 and one patient
      with diarrhea grade 4). In the low 5-FU group all six patients received >80% of
      the planned dose. In the high 5-FU group, seven of 14 patients (50%) received <
      or =80% of the planned chemotherapy dose during the first cycle due to dosage
      reductions whilst treatment delays occurred in 10/14 patients. During the whole
      study period, the common grade 3/4 adverse events were acne-like rash (38%) and
      diarrhea (29%). Chemotherapy did not affect the pharmacokinetics of cetuximab
      determined at weeks 1 and 4. Fourteen patients (67%, 95% CI 47% to 87%) had a
      confirmed response, and six (29%) had stable disease. Median time to progression
      was 9.9 months [lower 95% confidence limit (CL) 7.9, upper 95% CL not reached].
      Median survival time was 33 months (lower CL 20, upper CL not reached). Four
      patients received secondary surgery with curative intent, and a fifth was
      potentially eligible for surgery but declined. CONCLUSIONS: Addition of cetuximab
      to weekly infusional 5-FU/FA plus irinotecan is safe and first data suggest a
      promising activity. The 5-FU dose of 1500 mg/m(2) is recommended for further
      studies.

PMID- 16303862
TI  - Reply to the article "A monoclonal antibody against HER-2 (trastuzumab) for
      metastatic breast cancer: a model based cost-effectiveness analysis", by J. Norum
      et al. (Ann Oncol 2005; 16: 909-914).

PMID- 16303863
TI  - Oxaliplatin and capecitabine in patients with metastatic adenocarcinoma of the
      esophagus, gastroesophageal junction and gastric cardia: a phase II study from
      the North Central Cancer Treatment Group.
AB  - PURPOSE: The synergic combination of oxaliplatin and capecitabine has
      demonstrated activity against various gastrointestinal cancers, including colon
      cancer. We therefore undertook this phase II study to test this first-line
      combination in patients with metastatic adenocarcinoma of the esophagus,
      gastroesophageal junction and gastric cardia. PATIENTS AND METHODS: Forty-three
      patients with histologic or cytologic confirmation of the above malignancy were
      recruited. The cohort had Eastern Cooperative Oncology Group performance statuses
      of 0, 1 and 2 in 47%, 51%, and 2%, respectively. Median age was 61 years (range
      32-80). All had adequate organ function. Initially, patients were prescribed 130
      mg/m2 intravenously on day 1 and capecitabine 1000 mg/m2 orally twice a day, on
      days 1-14 of a 21-day cycle. Four treatment-related deaths in the first 24
      patients led to a reduction in capecitabine to 850 mg/m2 orally twice a day, days
      1-14, for the remainder of the cohort. RESULTS: The tumor response rate was 35%
      [95% confidence intervals (CI) 23% to 50%]. All responses were partial; seven of
      24 occurred before the capecitabine dose reduction, and eight of 19 after. Median
      time to tumor progression was 4 months (95% CI 3.1-4.6), and median survival 6.4
      months (95% CI 4.6-10). To date, there have been 36 deaths. Four were treatment
      related (one infection, two myocardial infarctions, one respiratory failure), and
      all occurred before the capecitabine dose reduction. Notable grade 4 events from
      the entire cohort included diarrhea (two patients), vomiting (three), dyspnea
      (one), thrombosis (two) and anorexia (two). Grade 3 events included nausea (12
      patients), diarrhea (12), fatigue (10), abdominal pain (seven), vomiting (six),
      dyspnea (six), hypokalemia (six), dehydration (five), hypokalemia (five) and
      infection (four). CONCLUSIONS: Oxaliplatin and capecitabine in combination
      demonstrates activity in metastatic adenocarcinoma of the esophagus,
      gastroesophageal junction and gastric cardia. The lower dose (capecitabine 850
      mg/m2 orally twice a day, days 1-14, and oxaliplatin 130 mg/m2 intravenously on
      day 1) yielded an acceptable toxicity profile and merits further study.

PMID- 16303864
TI  - Dose-finding and pharmacokinetic study of an all-oral combination regimen of oral
      vinorelbine and capecitabine for patients with metastatic breast cancer.
AB  - PURPOSE: A phase I study was performed to determine the maximal tolerated dose,
      recommended doses (RDs), safety and efficacy of oral vinorelbine when combined
      with capecitabine in an all-oral chemotherapy regimen in patients with metastatic
      breast cancer (MBC), with pharmacokinetic blood sampling to investigate potential
      drug-drug interactions. PATIENTS AND METHODS: Forty-four patients with MBC
      received as first- or second-line chemotherapy, oral vinorelbine at a dose of 60
      or 80 mg/m2 on days 1 and 8 (and 15) with escalating doses of capecitabine from
      1650 to 2500 mg/m2/day days 1-14 every 3 or 4 weeks. Three schedules were tested:
      day 1, day 8 and weekly regimens of oral vinorelbine with a 14-day course of
      capecitabine every 3 weeks; and a days 1 and 8 regimen of oral vinorelbine with a
      14-day course of capecitabine every 4 weeks. RESULTS: With oral vinorelbine at 60
      mg/m2, the RDs were established as oral vinorelbine 60 mg/m2 on days 1 and 8 plus
      capecitabine 2250 mg/m2/day days 1-14 and oral vinorelbine 60 mg/m2/week plus
      capecitabine 2000 mg/m2/day days 1-14. With oral vinorelbine at 80 mg/m2, the RD
      was oral vinorelbine 80 mg/m2 on days 1 and 8 plus capecitabine 2000 mg/m2/day
      days 1-14. Neutropenia was the main dose-limiting toxicity of the combination; it
      was reported in 40 patients (90.9%), with grade 3 in 14 patients (31.8%) and 6.2%
      of cycles, and grade 4 in 12 patients (27.3%) and 4.3% of cycles. Complications
      were rare with only three patients experiencing febrile neutropenia (one episode
      each). The most frequent non-haematological toxicity was gastrointestinal;
      however, the incidence of grade 3 was low, with no episode of grade 4. Hand-foot
      syndrome was reported in 14 patients (31.8%) and 22.6% of cycles, with grade 2 in
      two patients (4.5%) and 1.2% of cycles (two episodes each). No episode of grade 3
      was observed. Objective responses were reported in 18 patients (three complete
      responses and 15 partial responses), yielding a response rate of 40.9% in the
      intention-to-treat population according to the investigator assessment. Results
      from the pharmacokinetic study demonstrated the absence of mutual pharmacokinetic
      interactions when both drugs were co-administered. CONCLUSIONS: The combination
      of oral vinorelbine and capecitabine is safe and easy to administer in an
      outpatient setting. This all-oral combination chemotherapy may offer a good
      alternative to the intravenous route for patients with MBC. Based on these
      promising results, a phase II study has started using oral vinorelbine 60
      mg/m2/week with capecitabine 2000 mg/m2/day days 1-14 every 3 weeks as first-line
      chemotherapy in patients with MBC.

PMID- 16303865
TI  - A phase II trial of a combination of pemetrexed and gemcitabine in patients with
      metastatic breast cancer: an NCCTG study.
AB  - PURPOSE: This phase II study was undertaken to define the efficacy and toxicity
      of pemetrexed in combination with gemcitabine in patients with metastatic breast
      cancer. PATIENTS AND METHODS: Patients with measurable metastatic breast cancer
      who had previously received an anthracycline and a taxane in either the adjuvant
      or metastatic setting were treated with gemcitabine 1250 mg/m2 (intravenous; days
      1 and 8) and pemetrexed 500 mg/m2 (intravenous; day 8) every 21 days. RESULTS:
      Fifty-nine patients received a median of five cycles (range one to 22) of
      treatment and were followed until death or for a median of 28 months (range 19.4
      36.6) among living patients. Fourteen partial responses for an overall response
      rate of 24% [95% confidence interval (CI) 16% to 39%] were documented. Nine (15%;
      CI 5% to 32%) patients had stable disease for >6 months. The median survival time
      was 10.3 months (95% CI 8.3-18.9) and the 1 year survival rate was 49% (95% CI
      38% to 64%). The median time to progression was estimated to be 3.7 months (95%
      CI 2.3-5.3). The most common grade 3 or 4 toxicities were neutropenia and
      thrombocytopenia in 83% and 27% of patients, respectively. Fourteen percent of
      patients experienced febrile neutropenia. Other common grade 3 or 4 non
      hematological toxicities included fatigue (17%), dyspnea (15%), rash (7%) and
      anorexia (5%). CONCLUSIONS: The combination of pemetrexed and gemcitabine is
      clinically active, with an overall response rate of 24% in patients with
      metastatic breast cancer who have previously been treated with an anthracycline
      and a taxane. Myelosuppression (66% grade 4 neutropenia and 14% febrile
      neutropenia) was the major treatment-related toxicity observed for this
      combination.

PMID- 16303866
TI  - Adolescent smoking in pregnancy and birth outcomes.
AB  - INTRODUCTION: Cigarette smoking amongst pregnant adolescents is a preventable
      risk factor associated with low birthweight (<2,500 g), preterm birth (<37 weeks)
      and infant mortality. The aim of this study was to compare birth outcomes of
      adolescents who smoke during pregnancy with those who do not and to construct
      their birthweight-for-gestational-age curves. METHODS: A retrospective cohort
      analysis of 534 adolescents (<or=19 years) and 8972 adults who delivered
      singleton births between 1998-2003 at the Liverpool Women's Hospital. RESULTS:
      Adolescent pregnancy occurred in 5.6% of deliveries. Mean age of adolescents was
      18.1 years (SD = 1.0) and 46.2% smoked during pregnancy including 83.5% light
      smokers (<10 cigarettes daily). Babies born to adolescent smokers were
      significantly lighter by -170 g (P = 0.005). The prevalence of low birthweight
      was almost double in adolescents who smoked (12.1% versus 6.8%, RR = 1.7; CI =
      1.0-3.0), and their mean Apgar scores at 5 min were lower (<0.05). A higher
      prevalence of preterm birth (P < 0.05) and maternal anaemia (P < 0.01) occurred
      amongst adolescent smokers. Adolescents smoking >10 cigarettes daily had babies
      with larger birthweight reduction (P = 0.001). CONCLUSION: Almost half of all
      adolescents smoked during their pregnancy. Birthweight-for-gestational-age curves
      of smoking adolescents showed a marked fall-off in weight from 36 weeks of
      gestation, and at least 10% of adolescent smokers showed fetal growth restriction
      from before 32 weeks of gestation.

PMID- 16303867
TI  - The extracytoplasmic adaptor protein CpxP is degraded with substrate by DegP.
AB  - In Escherichia coli, the CpxR/A two-component system senses various types of
      extracytoplasmic stresses and responds by activating the expression of genes
      encoding periplasmic protein folding and trafficking factors that clear such
      stresses to ensure the organism's survival. The cpxP gene encodes a small, stress
      combative periplasmic protein and is the most strongly induced member of the Cpx
      regulon. We demonstrate that the Cpx stress response suppresses the toxicity
      associated with two misfolded proteins derived from the P pilus of uropathogenic
      E. coli and that mutations in either cpxP or the gene for the periplasmic
      protease DegP prevent suppression by preventing the degradation of these
      proteins. Strikingly, the presence of a periplasmic misfolded protein substrate
      significantly enhances the proteolysis of CpxP by DegP. Our data suggest that
      CpxP functions as a periplasmic adaptor protein that is required for the
      effective proteolysis of a subset of misfolded substrates by the DegP protease.

PMID- 16303868
TI  - A mechanism underlying AMPA receptor trafficking during cerebellar long-term
      potentiation.
AB  - Long-term potentiation (LTP) is mediated by the activity-driven delivery of GluR1
      glutamate receptors via Ca2+/calmodulin-dependent protein kinase II activity in
      various brain regions. Recently, postsynaptic LTP was shown to be induced at
      parallel fiber-Purkinje cell synapses by stimulating the parallel fibers at 1 Hz
      or applying a NO donor. Here, we demonstrate that NO-evoked postsynaptic LTP in
      mice cerebellum was blocked by botulinum toxin and enhanced by prior treatment
      with phorbol ester, which is known to induce GluR2 endocytosis. Interestingly,
      such LTP was not affected by a Ca2+/calmodulin-dependent protein kinase II
      inhibitor or a peptide binding to a protein interacting with C kinase 1, but was
      blocked by a peptide binding to N-ethylmaleimide-sensitive factor, which
      specifically binds to GluR2. Therefore, although the synaptic incorporation of
      GluR2 has been reported to be a constitutive pathway, NO-induced postsynaptic LTP
      in Purkinje cells is likely mediated by a pathway involving N-ethylmaleimide
      sensitive factor-dependent GluR2 trafficking.

PMID- 16303869
TI  - Inferring the in vivo looping properties of DNA.
AB  - The free energy of looping DNA by proteins and protein complexes determines to
      what extent distal DNA sites can affect each other. We inferred its in vivo value
      through a combined computational-experimental approach for different lengths of
      the loop and found that, in addition to the intrinsic periodicity of the DNA
      double helix, the free energy has an oscillatory component of about half the
      helical period. Moreover, the oscillations have such an amplitude that the
      effects of regulatory molecules become strongly dependent on their precise DNA
      positioning and yet easily tunable by their cooperative interactions. These
      unexpected results can confer to the physical properties of DNA a more prominent
      role at shaping the properties of gene regulation than previously thought.

PMID- 16303871
TI  - Brain cyclosporin A levels are determined by ontogenic regulation of mdr1a
      expression.
AB  - Cyclosporin A (CyA) toxicity is a common occurrence in pediatric organ transplant
      patients. We hypothesized that reduced mdr1a expression in newborn and developing
      mice would affect CyA accumulation within organs and/or toxicity. For functional
      studies, CyA was administered (5 mg kg(-1) i.p.) to 1-, 12-, and 19-day, and
      adult male and female mdr1a+/+ and mdr1a-/- mice. Peak blood CyA was lower in 1-,
      12-, and 19-day-old (1000 ng ml(-1)) versus adult (1500 ng ml(-1)) mice but was
      similar in mdr1a+/+ and mdr1a-/- mice. Kidney mdr1a expression (measured by
      quantitative polymerase chain reaction) increased 2.5-fold in 19-day-old male and
      female mice and increased another 4-fold in adult females compared with adult
      males. Liver mdr1a expression increased 6-fold by day 12 compared with neonatal
      mice. Thereafter, maintenance of hepatic mdr1a expression in females and a
      reduction to neonatal levels in males was observed. Kidney/blood (8- to 9-fold)
      and liver/blood (12- to 15-fold) CyA levels were highest on days 12 and 19 and
      were not dependent on maturational changes in mdr1a mRNA levels. Adults had
      higher brain expression of mdr1a mRNA (3-fold), a corresponding 5-fold increase
      in immunodetectable P-glycoprotein, and 80% lower brain accumulation of CyA
      compared with 1-day-old mice. Conversely, in mdr1a-null mice, brain/blood CyA was
      similar in newborn and adult mice. A similar pattern was observed for the brain
      accumulation of the mdr1a substrate 3H-digoxin. We conclude that the risk for
      central nervous system drug toxicity could be higher in neonates or young
      children as a consequence of underdeveloped P-glycoprotein.

PMID- 16303870
TI  - Early experience in humans is associated with changes in neuropeptides critical
      for regulating social behavior.
AB  - The formation of social attachments is a critical component of human
      relationships. Infants begin to bond to their caregivers from the moment of
      birth, and these social bonds continue to provide regulatory emotional functions
      throughout adulthood. It is difficult to examine the interactions between social
      experience and the biological origins of these complex behaviors because children
      undergo both brain development and accumulate social experience at the same time.
      We had a rare opportunity to examine children who were reared in extremely
      aberrant social environments where they were deprived of the kind of care-giving
      typical for our species. The present experiment in nature provides insight into
      the role of early experience on the brain systems underlying the development of
      emotional behavior. These data indicate that the vasopressin and oxytocin
      neuropeptide systems, which are critical in the establishment of social bonds and
      the regulation of emotional behaviors, are affected by early social experience.
      The results of this experiment suggest a potential mechanism whose atypical
      function may explain the pervasive social and emotional difficulties observed in
      many children who have experienced aberrant care-giving. The present findings are
      consistent with the view that there is a critical role for early experience in
      the development of the brain systems underlying basic aspects of human social
      behavior.

PMID- 16303872
TI  - Brain distribution of cetirizine enantiomers: comparison of three different
      tissue-to-plasma partition coefficients: K(p), K(p,u), and K(p,uu).
AB  - The objective of this study was to compare the blood-brain barrier (BBB)
      transport and brain distribution of levo- (R-CZE) and dextrocetirizine (S-CZE).
      Microdialysis probes, calibrated using retrodialysis by drug, were placed into
      the frontal cortex and right jugular vein of eight guinea pigs. Racemic CZE (2.7
      mg/kg) was administered as a 60-min i.v. infusion. Unbound and total
      concentrations of the enantiomers were measured in blood and brain with liquid
      chromatography-tandem mass spectrometry. The brain distribution of the CZE
      enantiomers were compared using the parameters K(p,) K(p,u,) K(p,uu), and
      V(u,br). K(p) compares total brain concentration to total plasma concentration,
      K(p,u) compensates for binding in plasma, whereas K(p,uu) also compensates for
      binding within the brain tissue and directly quantifies the transport across the
      BBB. V(u,br) describes binding within the brain. The stereoselective brain
      distribution indicated by the K(p) of 0.22 and 0.04 for S- and R-CZE,
      respectively, was caused by different binding to plasma proteins. The transport
      of the CZE enantiomers across the BBB was not stereoselective, since the K(p,uu)
      was 0.17 and 0.14 (N.S.) for S- and R-CZE, respectively. The K(p,uu) values show
      that the enantiomers are effluxed to a large extent across the BBB. The V(u,br)
      of approximately 2.5 ml/g brain was also similar for both the enantiomers, and
      the value indicates high binding to brain tissue. Thus, when determining
      stereoselectivity in brain distribution, it is important to study all factors
      governing this distribution, binding in blood and brain, and the BBB equilibrium.

PMID- 16303873
TI  - Molecular profiling of murine sensory neurons in the nodose and dorsal root
      ganglia labeled from the peritoneal cavity.
AB  - Vagal afferent neurons are thought to convey primarily physiological information,
      whereas spinal afferents transmit noxious signals from the viscera to the central
      nervous system. To elucidate molecular identities for these different properties,
      we compared gene expression profiles of neurons located in nodose ganglia (NG)
      and dorsal root ganglia (DRG) in mice. Intraperitoneal administration of Alexa
      Fluor-488-conjugated cholera toxin B allowed enrichment for neurons projecting to
      the viscera. Fluorescent neurons in DRG (from T10 to T13) and NG were isolated
      using laser-capture microdissection. Gene expression profiles of these afferent
      neurons, obtained by microarray hybridization, were analyzed using multivariate
      spectral map analysis, significance analysis of microarrays (SAM) algorithm, and
      fold-difference filtering. A total of 1,996 genes were differentially expressed
      in DRG vs. NG, including 41 G protein-coupled receptors and 60 ion channels.
      Expression profiles obtained on laser-captured neurons were contrasted to those
      obtained on whole ganglia, demonstrating striking differences and the need for
      microdissection when studying visceral sensory neurons because of dilution of the
      signal by somatic sensory neurons. Furthermore, we provide a detailed catalog of
      all adrenergic and cholinergic, GABA, glutamate, serotonin, and dopamine
      receptors; voltage-gated potassium, sodium, and calcium channels; and transient
      receptor potential cation channels present in afferents projecting to the
      peritoneal cavity. Our genome-wide expression profiling data provide novel
      insight into molecular signatures that underlie both functional differences and
      similarities between NG and DRG sensory neurons. Moreover, these findings will
      offer novel insight into mode of action of pharmacological agents modulating
      visceral sensation.

PMID- 16303874
TI  - Anti-proliferative and anti-inflammatory effects of topical MAPK inhibition in
      arterialized vein grafts.
AB  - Vein graft failure following bypass surgery is a frequent and important clinical
      problem. The vascular injury caused by arterialization is responsible for vein
      graft intimal hyperplasia, a lesion generated by medial smooth muscle cell
      proliferation and migration into the intima, increased extracellular matrix
      deposition, and formation of a thick neointima. Development of the neointima into
      a typical atherosclerotic lesion and consequent stenosis ultimately result in
      vein graft failure. Endothelial damage, inflammation, and intracellular signaling
      through mitogen-activated protein kinases (MAPKs) have been implicated in the
      early stages of this process. We therefore investigated the effects of topical
      inhibition of ERK-1/2 MAPK activation on vascular cell proliferation and
      apoptosis, and on the inflammatory response in a canine model of vein graft
      arterialization. For this purpose, vein grafts were incubated with the MEK-1/2
      inhibitor, UO126, ex vivo for 30 min before grafting. This treatment effectively
      abolished arterialization-induced ERK-1/2 activation, decreased medial cell
      proliferation, and increased apoptosis. UO126 treatment also inhibited the vein
      graft infiltration by myeloperoxidase-positive inflammatory cells that follows
      vein graft arterialization. Thus, topical ex vivo administration of MAPK
      inhibitors can provide a pharmacological tool to prevent or reduce the vascular
      cell responses that lead to vein graft intimal hyperplasia and graft failure.

PMID- 16303875
TI  - Ligamentous posttraumatic ankle osteoarthritis.
AB  - BACKGROUND: Ankle sprains are the most common injuries in sports and recreational
      activities. HYPOTHESIS: Ankle osteoarthritis can be caused by ankle ligament
      lesions. Latency time between injury and osteoarthritis is influenced by the type
      and side of the injured ligaments. The side of the ligamentous lesion correlates
      with the hindfoot alignment. STUDY DESIGN: Case series; Level of evidence, 4.
      METHODS: Of a cohort of 247 patients with ankle arthritis, we reviewed data from
      30 patients (33 ankles; mean age, 58.6 years) with ligamentous end-stage ankle
      osteoarthritis. The patients were evaluated etiologically, clinically, and
      radiologically. RESULTS: Etiologic analysis: 55% had a ligamentous lesion from
      sports injuries (soccer, 33%); 85% injured the lateral ankle ligaments, and 15%
      injured the medial and medial-lateral ligaments. The mean latency time between
      injury and osteoarthritis was 34.3 years. The survivorship rate for single severe
      ankle sprains was worse than that for chronic recurrent ligamentous lesions (mean
      latency time, 25.7 vs 38.0 years; P < .05), and the rate for medial sprains was
      worse than for lateral sprains (mean latency time, 27.5 vs 35.0 years; P < .05).
      At follow-up, the American Orthopaedic Foot and Ankle Society hindfoot score was
      23.0 points, 52% had varus malalignment, 52% had persistent instability, and the
      mean ankle arthritis grade was 2.6 points. There was a correlation between
      chronic lateral ankle instability and varus malalignment. CONCLUSION: Lateral
      ankle sprains in sports are the main cause of ligamentous posttraumatic ankle
      osteoarthritis and correlate with varus malalignment. At the time of end-stage
      ligamentous ankle osteoarthritis, persistent instability may be encountered.

PMID- 16303876
TI  - Injuries in team sport tournaments during the 2004 Olympic Games.
AB  - BACKGROUND: Several authors have analyzed the incidence of injuries in a given
      sport, but only a few have examined the exposure-related incidence of injuries in
      different types of sports using the same methodology. PURPOSE: Analysis of the
      incidence, circumstances, and characteristics of injuries in different team
      sports during the 2004 Olympic Games. STUDY DESIGN: Cohort study; Level of
      evidence, 2. METHODS: During the 2004 Olympic Games, injuries in 14 team sport
      tournaments (men's and women's soccer, men's and women's handball, men's and
      women's basketball, men's and women's field hockey, baseball, softball, men's and
      women's water polo, and men's and women's volleyball) were analyzed. After each
      match, the physician of the participating teams or the official medical
      representative of the sport completed a standardized injury report form. The mean
      response rate was 93%. RESULTS: A total of 377 injuries were reported from 456
      matches, an incidence of 0.8 injuries per match (95% confidence interval, 0.75
      0.91) or 54 injuries per 1000 player matches (95% confidence interval, 49-60).
      Half of all injuries affected the lower extremity; 24% involved the head or neck.
      The most prevalent diagnoses were head contusion and ankle sprain. On average,
      78% of injuries were caused by contact with another player. However, a
      significantly higher percentage of noncontact (57%) versus contact injuries (37%)
      was expected to prevent the player from participating in his or her sport.
      Significantly more injuries in male players (46%) versus female players (35%)
      were expected to result in absence from match or training. The incidence,
      diagnosis, and causes of injuries differed substantially between the team sports.
      CONCLUSION: The risk of injury in different team sports can be compared using
      standardized methodology. Even if the incidence and characteristics of injuries
      are not identical in all sports, prevention of injury and promotion of fair play
      are relevant topics for almost all team sports.

PMID- 16303877
TI  - Glenohumeral range of motion deficits and posterior shoulder tightness in
      throwers with pathologic internal impingement.
AB  - BACKGROUND: Alterations in glenohumeral range of motion, including increased
      posterior shoulder tightness and glenohumeral internal rotation deficit that
      exceeds the accompanying external rotation gain, are suggested contributors to
      throwing-related shoulder injuries such as pathologic internal impingement. Yet
      these contributors have not been identified in throwers with internal
      impingement. HYPOTHESIS: Throwers with pathologic internal impingement will
      exhibit significantly increased posterior shoulder tightness and glenohumeral
      internal rotation deficit without significantly increased external rotation gain.
      STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: Eleven throwing
      athletes with pathologic internal impingement diagnosed using both clinical
      examination and a magnetic resonance arthrogram were demographically matched with
      11 control throwers who had no history of upper extremity injury. Passive
      glenohumeral internal and external rotation were measured bilaterally with
      standard goniometry at 90 degrees of humeral abduction and elbow flexion.
      Bilateral differences in glenohumeral range of motion were used to calculate
      glenohumeral internal rotation deficit and external rotation gain. Posterior
      shoulder tightness was quantified as the bilateral difference in passive shoulder
      horizontal adduction with the scapula retracted and the shoulder at 90 degrees of
      elevation. Comparisons were made between groups with dependent t tests (P < .05).
      RESULTS: The throwing athletes with internal impingement demonstrated
      significantly greater glenohumeral internal rotation deficit (P = .03) and
      posterior shoulder tightness (P = .03) compared with the control subjects. No
      significant differences were observed in external rotation gain between groups (P
      = .16). CLINICAL RELEVANCE: These findings could indicate that a tightening of
      the posterior elements of the shoulder (capsule, rotator cuff) may contribute to
      impingement. The results suggest that management should include stretching to
      restore flexibility to the posterior shoulder.

PMID- 16303878
TI  - Tension-band wiring for fractures of the fifth metatarsal located in the junction
      of the proximal metaphysis and diaphysis.
AB  - BACKGROUND: Fractures of the proximal fifth metatarsal, other than those
      involving the tuberosity, have a tendency to delayed union or even nonunion.
      HYPOTHESIS: Tension-band wire technique is a good alternative in treating
      fractures of the fifth metatarsal located in the proximal junction of the
      metaphysis and the diaphysis. STUDY DESIGN: Case series; level of evidence, 4.
      METHODS: Between 1996 and 2001, a total of 27 cases of proximal
      metaphysial/diaphysial fractures of the fifth metatarsal were treated with
      tension-band wiring. All of the patients had undergone prior unsuccessful
      nonoperative or operative treatment. The mean delay from the diagnosis of the
      fracture to the final operative procedure was 19.5 weeks (range, 6-48 weeks).
      RESULTS: The mean length of follow-up was 35 months (range, 12-70 months). All
      patients were able to return to their prior levels of activity. The mean time for
      union as shown on radiographs was 12.8 weeks, and the return to full activity
      took 8 to 20 weeks (mean, 14.7 weeks). There were no delayed unions, nonunions,
      or refractures during the follow-up. CONCLUSION: The tension-band wire technique
      seems to give good results in the treatment of proximal metaphysial/diaphysial
      fractures of the fifth metatarsal in cases of primary unsuccessful nonoperative
      treatment or primary unsuccessful intramedullary screw fixation.

PMID- 16303879
TI  - Anatomical glenoid reconstruction for recurrent anterior glenohumeral instability
      with glenoid deficiency using an autogenous tricortical iliac crest bone graft.
AB  - BACKGROUND: Anterior shoulder instability associated with severe glenoid bone
      loss is rare, and little has been reported on this problem. Recent biomechanical
      and anatomical studies have suggested guidelines for bony reconstruction of the
      glenoid. HYPOTHESIS: Anatomical glenoid reconstruction will restore stability in
      shoulders with recurrent anterior instability owing to glenoid bone loss. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: Eleven cases of traumatic
      recurrent anterior instability that required bony reconstruction for severe
      anterior glenoid bone loss were reviewed. In all cases, the length of the
      anterior glenoid defect exceeded the maximum anteroposterior radius of the
      glenoid based on preoperative assessment by 3-dimensional CT scan. Surgical
      reconstruction was performed using an intra-articular tricortical iliac crest
      bone graft contoured to reestablish the concavity and width of the glenoid. The
      graft was fixed with cannulated screws in combination with an anterior-inferior
      capsular repair. RESULTS: At mean follow-up of 33 months, the mean American
      Shoulder and Elbow Surgeons score was 94, compared with a preoperative score of
      65. The University of California, Los Angeles score improved to 33 from 18. The
      Rowe score improved to 94 from a preoperative score of 28. The mean motion loss
      compared with the contralateral, normal shoulder was 7 degrees of flexion, 14
      degrees of external rotation in abduction, and one spinous process level for
      internal rotation. All patients returned to preinjury levels of sport, and only 2
      complained of mild pain with overhead sports activities. No patients reported any
      recurrent instability (dislocation or subluxation). The CT scans with 3
      dimensional reconstructions obtained 4 to 6 months postoperatively demonstrated
      union of the bone graft with incorporation along the anterior glenoid rim and
      preservation of joint space. CONCLUSION: Anatomical reconstruction of the glenoid
      with autogenous iliac crest bone graft for recurrent glenohumeral instability in
      the setting of bone deficiency is an effective form of treatment for this
      problem.

PMID- 16303880
TI  - Importance of femoral tunnel placement in double-bundle posterior cruciate
      ligament reconstruction: biomechanical analysis using a robotic/universal force
      moment sensor testing system.
AB  - BACKGROUND: Previous studies have identified the femoral attachment of the
      posterior cruciate ligament fibers as one of the primary determinants of fiber
      tension behavior. In addition, a double-bundle posterior cruciate ligament
      reconstruction has been shown to restore the intact knee kinematics more closely
      than does a single-bundle reconstruction. HYPOTHESIS: An anterior tunnel position
      in double-bundle posterior cruciate ligament reconstruction restores the
      biomechanics of the normal knee more closely than does a posterior tunnel
      position. STUDY DESIGN: Controlled laboratory study. METHODS: Kinematics and in
      situ forces of human knees after double-bundle posterior cruciate ligament
      reconstruction with 2 different femoral tunnel positions (anterior vs posterior)
      were evaluated using a robotic/universal force-moment sensor testing system.
      Within the same specimen, the resulting knee kinematics and in situ forces were
      compared. For statistical analysis, 2-way analysis of variance repeated measures
      were performed. RESULTS: The femoral tunnel position of the double-bundle
      hamstring graft had significant effect on the resulting posterior tibial
      displacement and in situ forces of the hamstring grafts. The anterior femoral
      tunnel position provided significantly less posterior tibial translation than did
      the posterior tunnel position. There was a tendency toward higher in situ forces
      of grafts fixed in the anterior tunnel when compared to the posterior position,
      but this difference was statistically not significant. CONCLUSION: An anterior
      position of the bone tunnels in double-bundle posterior cruciate ligament
      reconstruction restores the normal knee kinematics more closely than does a
      posterior position of the tunnels. CLINICAL RELEVANCE: In double-bundle posterior
      cruciate ligament reconstruction, posterior placement of the tunnel should be
      avoided.

PMID- 16303881
TI  - Arthroscopic transtibial posterior cruciate ligament reconstruction with
      preservation of posterior cruciate ligament fibers: clinical results of minimum 2
      year follow-up.
AB  - BACKGROUND: The transtibial technique for posterior cruciate ligament
      reconstructions can potentially lead to poor clinical outcomes due to the "killer
      turn" effect. HYPOTHESIS: Preserving the original posterior cruciate ligament
      fibers in the reconstruction will contribute significantly to the posterior
      stability of the knee joint, healing of the graft, and prevention of graft
      failure. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Sixty-one
      patients (45 men and 16 women; mean age, 30.4 years) underwent transtibial
      posterior cruciate ligament reconstruction with preservation of the cruciate
      ligament fibers; they were reviewed at a mean period of 40.8 months. All patients
      were assessed with the Lysholm knee score, International Knee Documentation
      Committee subjective and objective evaluations, and KT-2000 arthrometry. Follow
      up magnetic resonance imaging was performed in 40 patients; images were assessed
      for graft continuity, thickness, and signal intensity. Second-look arthroscopy
      was performed in 42 patients. RESULTS: The mean Lysholm score improved from 65.8
      to 92.9. The final International Knee Documentation Committee subjective
      evaluation rated all patients as normal or nearly normal, and the objective
      evaluation showed normal or nearly normal in 59 patients (97%) and abnormal in 2
      patients (3%). The mean side-to-side difference on the KT-2000 arthrometer was
      2.79 mm. All patients showed well-preserved graft continuity on magnetic
      resonance images. Mean graft thickness was 9.9 mm in the sagittal plane and 12.3
      mm in the coronal oblique plane. Images for all patients revealed homogeneously
      low signal intensity in the distal portion of the graft, with complete healing of
      the graft and original posterior cruciate ligament fibers as one ligament. Graft
      loosening or graft tear by the killer turn effect was not detected in any
      patients. Second-look arthroscopy revealed complete healing and graft
      integration, with the original posterior cruciate ligament fibers in all
      patients. CONCLUSION: In transtibial posterior cruciate ligament reconstructions,
      poor outcomes from the killer turn effect may be reduced by preserving the
      original posterior cruciate ligament fibers.

PMID- 16303882
TI  - Interaction of CmeABC and CmeDEF in conferring antimicrobial resistance and
      maintaining cell viability in Campylobacter jejuni.
AB  - OBJECTIVES: To determine the role of CmeDEF in conferring antimicrobial
      resistance in Campylobacter jejuni and examine the interaction of CmeABC and
      CmeDEF in mediating antimicrobial resistance and maintaining cell viability.
      METHODS: Single and double mutants of cmeF and cmeB were generated in multiple
      strains using insertional mutagenesis. The mutants were compared with their wild
      type strains for antimicrobial susceptibility and growth characteristics.
      Transcription fusion was used to quantify the expression of cmeDEF and cmeABC.
      Ethidium bromide (EB) accumulation assay was used to measure the efflux function.
      RESULTS: Insertional mutagenesis of the cmeF gene in C. jejuni NCTC 11168
      resulted in a 2-fold decrease in the resistance to ampicillin, polymyxin B and
      EB, whereas the same mutation in C. jejuni 81-176 and 21190 led to a 2-4-fold
      increase in the resistance to multiple antimicrobials and toxic compounds. The
      increased resistance in the cmeF mutants of 81-176 and 21190 was associated with
      the elevated efflux in the mutants. Compared with the cmeB mutant, the cmeF/cmeB
      double mutants of 81-176 and 21190 showed further decrease in the resistance to
      various antimicrobials and toxic compounds. Transcription fusion assay indicated
      that the expression level of cmeF was substantially lower than that of cmeB.
      Notably, the cmeB/cmeF double mutation, not the single mutations, impaired cell
      viability in Campylobacter. CONCLUSIONS: CmeDEF interacts with CmeABC in
      conferring antimicrobial resistance and maintaining cell viability in C. jejuni.
      CmeABC is the predominant efflux pump in C. jejuni, whereas CmeDEF plays a
      secondary role in conferring intrinsic resistance to antimicrobials.

PMID- 16303883
TI  - Antimicrobial activity of picolinic acid against extracellular and intracellular
      Mycobacterium avium complex and its combined activity with clarithromycin,
      rifampicin and fluoroquinolones.
AB  - OBJECTIVES: A natural metal ion chelator, picolinic acid (PA), is known to
      potentiate macrophage antimycobacterial activity. Here, we studied the
      antimicrobial activity of PA against extracellular and intramacrophage
      Mycobacterium avium complex (MAC) organisms. METHODS: MAC organisms, MAC-infected
      macrophages or MAC-infected type II pneumocytes were cultured in the presence or
      absence of PA with or without antimycobacterial drugs, and residual bacterial cfu
      of extracellular or intracellular MAC were counted on 7H11 agar plates. RESULTS:
      First, PA exhibited antimicrobial activity against extracellular and
      intramacrophage MAC. The effect of PA was mimicked by other metal ion-chelating
      agents, such as ethylenediamine tetraacetic acid and O,O'-bis (2-aminophenyl)
      ethyleneglycol-N,N,N',N'-tetraacetic acid. Second, PA potentiated antimicrobial
      effects of a two-drug combination of clarithromycin/rifampicin and some
      fluoroquinolones (levofloxacin, sitafloxacin and gatifloxacin) against
      extracellular and intramacrophage MAC. Similar combined effects of PA with
      clarithromycin/rifampicin were also seen in the case of MAC residing within type
      II alveolar epithelial cells. CONCLUSIONS: PA exerted an appreciable anti-MAC
      activity, when used singly or in combination with some antimycobacterial drugs
      (clarithromycin/rifampicin and fluoroquinolones), suggesting the usefulness of PA
      as an adjunct for clinical antimicrobial chemotherapy of MAC infections.

PMID- 16303884
TI  - Warfarin initiation and the potential role of genomic-guided dosing.

PMID- 16303885
TI  - Impact of age, CYP2C9 genotype and concomitant medication on the rate of rise for
      prothrombin time during the first 30 days of warfarin therapy.
AB  - OBJECTIVES: To characterize the impact of several important clinical variables on
      the rate of anticoagulation during warfarin initiation (i.e., the first 30 days).
      DESIGN: Retrospective study. SETTING: An anticoagulation service of a large
      horizontally integrated, multispecialty group practice in central and northern
      Wisconsin. PARTICIPANTS: Patients with sufficient laboratory data obtained during
      the initiation phase of warfarin treatment. METHODS: Patients were consented and
      genotyped for cytochrome P450 (CYP) 2C9 polymorphisms. Anticoagulation laboratory
      data were then electronically abstracted and fitted to a logistic growth model.
      Rate of anticoagulation was compared between groups. RESULTS: During warfarin
      initiation, the mean slope for rise in International Normalized Ratio (INR) of
      prothrombin time was significantly associated with age (p = 0.03, n = 166).
      Because a relationship between diabetes and warfarin dosing has been suggested
      previously, we assessed the impact of this comorbidity in our model as well.
      Diabetes showed relatively little impact, but concomitant treatment with an anti
      diabetic sulfonylurea medication was associated with an increase in slope (3
      fold, p < 0.05). Since this drug interaction may occur at the level of CYP2C9, we
      also assessed the impact of CYP2C9 genotype in our model. The impact of CYP2C9
      genotype was marginally significant (p = 0.119, non-pooled dataset; p = 0.053,
      data pooled for CYP2C9 *2/*2, *2/*3 and *3/*3). CONCLUSIONS: Age and concomitant
      sulfonylurea therapy alter the rate of anticoagulation during the first 30 days
      of warfarin therapy.

PMID- 16303886
TI  - Efficacy of the influenza vaccine in patients with malignant lymphoma.
AB  - BACKGROUND: The benefits and efficacy of the influenza vaccine have been
      controversial and have had mixed reviews in the recent literature.
      Immunosuppressed patients and those receiving chemotherapy are particularly at
      risk for infectious complications and are therefore given high priority to
      receiving prophylactic vaccines. METHOD: We administered the influenza vaccine to
      29 patients with malignant lymphoma who were receiving chemotherapy or had
      recently completed therapy during the flu season of 2003-2004. An aged-matched
      control group received the same vaccine during the same period. The ability of
      both groups to mount a protective titer of antibodies to the antigens in the
      vaccine was measured. RESULTS: Three of 29 patients (10%) in the lymphoma group
      were able to mount a 4-fold titer to at least one of the influenza A antigens.
      One patient developed a protective titer to both influenza A and B antigens and 3
      of 29 responded to the influenza B antigen. In the control group 13 of 29 (45%)
      responded to an influenza A antigen and 14 of 29 (48%) had a 4-fold response to
      the B antigen. Seven of 29 controls (24%) had a 4-fold increase in their titers
      to both the A and B antigens. CONCLUSIONS: This study confirmed the low incidence
      of response or efficacy to the influenza vaccine reported in previous studies.
      Only a small percentage (10%) of immunosuppressed patients with malignant
      lymphoma responded with a 4-fold increase in their antibody titer to the major
      antigens of the 2003 influenza vaccine. Most interestingly, less than 50% of the
      aged-matched control population studied responded with a 4-fold increase in their
      antibody titer. Additional studies are needed to determine methods for improving
      the efficacy of the vaccine and the effectiveness of the influenza vaccination
      program in preventing influenza infections in the United States.

PMID- 16303887
TI  - Lung cancer immunotherapy.
AB  - Recent insights into anti-tumor immunotherapy have led to a wave of clinical
      trials involving immunotherapy for lung cancer. Vaccines have evolved from
      nonspecific immune stimulants, like Bacillus Calmette-Guerin (BCG), to much more
      specific and potent strategies, some of which generate active immune responses
      against tumor-associated antigens. Understanding the mechanisms of anti-tumor
      immunity and identifying target antigens will likely improve these therapeutic
      strategies and provide them with a niche in the future of lung cancer therapy.

PMID- 16303888
TI  - Periventricular heterotopia: new insights into Ehlers-Danlos syndrome.
AB  - Nature often employs similar mechanisms to complete similar tasks, thus the
      evolution of homologous proteins across various organ systems to perform similar
      but slightly different functions. In this respect, disorders attributed to
      specific genetic mutations, while initially thought to be restricted in function
      and purpose, may provide broad insight into general cellular and molecular
      mechanisms of development and maintenance. One such example can be seen in the
      brain malformation, periventricular heterotopia (PH), which is characterized by
      very specific nodules of neurons that line the lateral ventricles beneath the
      cerebral cortex. PH is seen as a disorder of neuronal migration and can be caused
      by mutations in filamin A (FLNA), which encodes an actin-binding protein that
      regulates the cytoskeleton and cell motility. Recent advances in our
      understanding of the genetic causes of PH suggest that mutations in this gene,
      however, are also associated with the connective tissue disorder, Ehlers-Danlos
      syndrome (EDS), in which affected individuals present with joint and skin
      hyperextensibility and vascular problems including aortic dissection, excessive
      bleeding and bruisability. While much still remains unknown regarding the
      mechanistic role of FLNA in giving rise to PH and EDS, a common cellular and
      molecular basis likely gives rise to these two seemingly unrelated clinical
      disorders.

PMID- 16303889
TI  - Tolerance induction by viral in vivo gene transfer.
AB  - Treatment of genetic disease by protein or gene replacement therapy is hampered
      by immune responses to the therapeutic protein. An excellent example is formation
      of inhibitory antibodies to coagulation factors in treatment of the X-linked
      bleeding disorder hemophilia. Experiments in murine and canine models of
      hemophilia B (deficiency in factor IX) have demonstrated sustained therapeutic
      levels of factor IX transgene expression following hepatic adeno-associated viral
      gene transfer in animals with deletion and nonsense mutations in the factor IX
      gene. This article reviews experimental evidence for induction of immune
      tolerance to the factor IX transgene product by hepatic adeno-associated viral
      gene transfer, which has been shown to limit T helper cell responses and to
      substantially reduce the risk of antibody responses. Tolerance induction is
      associated with activation of regulatory CD4(+) T cells capable of suppressing
      antibody formation to factor IX protein. Hepatic administration of adeno
      associated viral vector expressing ovalbumin in mice transgenic for a T cell
      receptor specific for this antigen provided direct evidence for induction of
      CD4(+) T cell tolerance, including T cell anergy and clonal deletion. Taken
      together, these data indicate the potential for viral in vivo gene transfer not
      only to provide sustained systemic expression, but moreover to induce
      immunological hypo-responsiveness to the therapeutic gene product.

PMID- 16303895
TI  - Standards-setting group seeks to improve medication adherence.

PMID- 16303896
TI  - Better renal-function estimates not expected to alter drug dosing right away.

PMID- 16303890
TI  - Relaxin: antifibrotic properties and effects in models of disease.
AB  - Fibrosis (progressive scarring) is a leading cause of organ failure worldwide and
      causes loss of organ function when normal tissue is replaced with excess
      connective tissue. Several organs are prone to this process regardless of
      etiology. The pleiotropic hormone, relaxin, is emerging as a novel antifibrotic
      therapy. Relaxin has been shown to limit collagen production and reorganization,
      while stimulating increased collagen degradation. It not only prevents
      fibrogenesis, but also reduces established scarring. This review summarizes (1)
      the levels at which relaxin inhibits collagen production and existing collagen
      overexpression in induced models of fibrosis, and (2) the collagen-related
      phenotypes of relaxin- and LGR7-deficient mice. Recent studies on relaxin
      deficient mice have established relaxin as an important, naturally occurring
      regulator of collagen turnover and provide new insights into the therapeutic
      potential of relaxin.

PMID- 16303897
TI  - Residency program fills medication safety void.

PMID- 16303898
TI  - Language, reporting of safety undergoing change.

PMID- 16303899
TI  - Visual compatibility of atosiban acetate with four drugs.

PMID- 16303900
TI  - Pharmacy technicians supporting clinical functions.

PMID- 16303901
TI  - The value of mentorship.

PMID- 16303902
TI  - Moving beyond balance for a better antidepressant.

PMID- 16303903
TI  - Duloxetine: a balanced and selective norepinephrine- and serotonin-reuptake
      inhibitor.
AB  - PURPOSE: The pharmacology, pharmacokinetics, efficacy, safety, drug interactions,
      dosage and administration, cost, and place in therapy of duloxetine for major
      depression, pain from diabetic peripheral neuropathy, and stress urinary
      incontinence are reviewed. SUMMARY: Duloxetine is a balanced selective serotonin
      and norepinephrine-reuptake inhibitor available in the United States for the
      treatment of major depressive disorder (MDD) and diabetic peripheral neuropathic
      pain (DPNP). Duloxetine has also been used for the treatment of stress urinary
      incontinence (SUI). Absorption of duloxetine begins two hours after oral
      administration, reaching a maximum plasma concentration in six hours. Half-life
      and volume of distribution are 12 hours and 1640 L, respectively. The recommended
      dosage of duloxetine is 40-80 mg daily, depending on the indication, preferably
      split into two doses per day. For the treatment of major depression, duloxetine
      has achieved remission rates similar to that of existing selective serotonin
      reuptake inhibitors (SSRIs). For SUI and pain associated with diabetic peripheral
      neuropathy, duloxetine has not demonstrated equivalence or superiority to
      existing therapies. The adverse effects of duloxetine are similar to those of
      traditional SSRIs. Nausea is common and has been cited as the primary reason for
      discontinuation of duloxetine in trials. Increases in blood pressure have been
      mild, but caution should be used in patients with hypertension. Patients with a
      creatinine clearance of <30 mL/min and patients with hepatic impairment should
      avoid duloxetine. Duloxetine should not be recommended as first-line therapy for
      SUI or DPNP. For MDD, duloxetine may be a useful alternative for patients who do
      not benefit from or are unable to tolerate other antidepressant therapy.
      CONCLUSION: Duloxetine has been approved for the treatment of MDD and pain
      associated with diabetic peripheral neuropathy in adults.

PMID- 16303904
TI  - Effects of morning versus evening administration of atorvastatin in patients with
      hyperlipidemia.
AB  - PURPOSE: The effects of morning versus evening administration of atorvastatin in
      hyperlipidemic patients were studied. METHODS: Patients whose care was managed by
      a teaching hospital run by the Department of Veterans Affairs who were prescribed
      atorvastatin calcium 40 mg p.o. daily by their primary care physician were
      interviewed by a clinical pharmacist in the ambulatory care clinic for study
      enrollment. Patients were excluded if they had diseases or conditions or took
      medication known to affect serum lipoprotein levels, as were patients who
      consumed more than three alcoholic drinks per day and those who could not verify
      the time of atorvastatin administration. Blood samples were collected after a 12
      hour fasting period and serum lipoprotein levels were measured at baseline and
      after four weeks. RESULTS: Of the 204 hyperlipidemic patients receiving
      atorvastatin, 64 met the inclusion criteria and were enrolled in the study, 32 of
      whom took the drug in the morning (before noon) and an equal number who took the
      drug at night (after 6 p.m. but before midnight). All patients were male
      outpatients with a mean +/- S.D. age of 57.8 +/- 7.8 years and 58.5 +/- 7.8 years
      for the morning and evening administration groups, respectively. No statistically
      significant differences in lipid values measured were found between the morning
      and evening administration group after four weeks. CONCLUSION: Changes in the
      levels of total cholesterol, low-density-lipoprotein cholesterol, triglycerides,
      and high-density-lipoprotein cholesterol were similar among hyperlipidemic
      patients receiving atorvastatin calcium 40 mg, regardless of the time of day the
      drug was administered.

PMID- 16303905
TI  - Medication use as a risk factor for falls among hospitalized elderly patients.
AB  - PURPOSE: The relationship between medication use and falls among hospitalized
      elderly patients was studied. METHODS: Sixty-two patients 65 years of age or
      older who fell during hospitalization were randomly selected from incident
      reports of falls and matched for age, sex, and discharge date with 62 patients
      who did not fall. Data on demographic characteristics, vital signs, laboratory
      test variables, drug therapy, and the presence of other known risk factors for
      falls were collected retrospectively and compared between the groups. RESULTS:
      Nonsteroidal antiinflammatory drug (NSAID) use was more frequent in patients who
      fell than in control patients. NSAID use was a significant predictor of falls and
      was associated with a 10-fold increase in the likelihood of falling. Opioid
      analgesics were given more frequently to control patients and were not associated
      with falls. Dementia, the only non-medication-related independent predicator of
      falls, was associated with a 21-fold greater risk of falling. CONCLUSION: In
      hospitalized elderly patients, there was a significant association between NSAID
      use and falls, an effect largely accounted for by low-dose aspirin.

PMID- 16303906
TI  - Advancing patient care through innovative practice: the Clinical Partners
      Program.
AB  - PURPOSE: The development, implementation, and outcomes assessment of an
      innovative pharmacist-managed ambulatory care and community pharmacy practice
      clinic are described. SUMMARY: The Clinical Partners Program at The Ohio State
      University (OSU) provides an active learning environment for students and
      residents, offers a patient-focused practice model based on pharmaceutical care
      principles, and serves as an arena for applied research in pharmacy practice. The
      program offers multiple services, including anticoagulation management, diabetes
      self-management, cholesterol management, hepatitis C education, herbal product
      and dietary supplement consultations, medication management, smoking cessation,
      and wellness. The practice is currently staffed by two faculty members from the
      college of pharmacy, with a 0.8 full-time-equivalent (FTE) pharmacist and a 0.65
      FTE community pharmacy resident. It has served as a training site for 17 pharmacy
      residents, 28 bachelor of science (B.S.) in pharmacy students, 30 post-B.S.
      doctor of pharmacy (Pharm.D.) students, and 132 entry-level Pharm.D. students at
      various levels of training. The most successful methods of reimbursement for
      programs have been contracted services with OSU Managed Health Care Systems,
      Inc., which serves OSU faculty and staff and fee-for-service billing, charged
      directly to non-OSU patients. Numerous studies have shown that Clinical Partners
      has consistently demonstrated improved therapeutic outcomes over those achieved
      in traditional practice. Faculty are exploring outreach services, including the
      development of advanced practice community sites for the college, establishing
      patient care services within physician offices, and providing disease management
      services for self-insured employers. CONCLUSION: The Clinical Partners Program
      has improved patient care and provided education and training opportunities for
      pharmacy students and residents.

PMID- 16303907
TI  - Self-prescribing of noncontrolled substances among pharmacists.

PMID- 16303908
TI  - Frequency and complexity of queries to an academic drug information center, 1995
      2004.

PMID- 16303909
TI  - Expansion of drug information services in response to an increased clerkship
      teaching load.

PMID- 16303910
TI  - Stability of anhydrous theophylline in extemporaneously prepared alcohol-free
      oral suspensions.

PMID- 16303911
TI  - Possible drug rash with eosinophilia and systemic symptoms syndrome after
      exposure to epoetin alfa.

PMID- 16303912
TI  - Influencing prescribing through effective communication skills.

PMID- 16303913
TI  - Student rotations in health-system pharmacy management and leadership.

PMID- 16303915
TI  - Pharmacy in Jordan.

PMID- 16303914
TI  - Updating the Pharmacy Technician Certification Examination: a practice analysis
      study.

PMID- 16303916
TI  - Immunomodulatory effects of etanercept in an experimental model of spinal cord
      injury.
AB  - Etanercept is a tumor necrosis factor antagonist with anti-inflammatory effects.
      The aim of our study was to evaluate for the first time the therapeutic efficacy
      of in vivo inhibition of tumor necrosis factor-alpha (TNF-alpha) in experimental
      model of spinal cord trauma, which was induced by the application of vascular
      clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. Spinal cord
      injury in mice resulted in severe trauma characterized by edema, neutrophil
      infiltration, and cytokine production that it is followed by recruitment of other
      inflammatory cells, such as production of a range of inflammation mediators,
      tissue damage, apoptosis, and disease. Treatment of the mice with etanercept
      significantly reduced the degree of 1) spinal cord inflammation and tissue injury
      (histological score); 2) neutrophil infiltration (myeloperoxidase evaluation); 3)
      inducible nitric-oxide synthase, nitrotyrosine, cyclooxygenase-2, and cytokines
      expression (TNF-alpha and interleukin-1beta); and 4) apoptosis (terminal
      deoxynucleotidyl transferase dUTP nick-end labeling staining and Bax and Bcl-2
      expression). In a separate set of experiment, we have also clearly demonstrated
      that TNF-alpha inhibitor significantly ameliorated the recovery of limb function
      (evaluated by motor recovery score). Taken together, our results clearly
      demonstrate that treatment with etanercept reduces the development of
      inflammation and tissue injury events associated with spinal cord trauma.

PMID- 16303917
TI  - Pharmacologic characterization of intrinsic mechanisms controlling tone and
      relaxation of porcine lower esophageal sphincter.
AB  - The neurotransmitters mediating relaxation of lower esophageal sphincter (LES)
      were studied using circular LES strips from adult pigs in organ baths. LES
      relaxation by sodium nitroprusside (1 nM-3 microM), vasoactive intestinal peptide
      (VIP) and pituitary adenylate cyclase-activating peptide (PACAP; 1 nM-1 microM),
      ATP (10 microM-30 mM), and tricarbonyldichlororuthenum dimer (1 microM-1 mM) was
      unaffected by tetrodotoxin (1 microM) or l-N(G)-nitroarginine methyl ester (l
      NAME; 100 microM). Calcitonin gene-related peptide (CGRP; 1 nM-1 microM) did not
      affect LES tone. ATP relaxation was blocked by 1 microM apamin and the P2Y(1)
      antagonist MRS 2179 (N6-methyl 2'-deoxyadenosine 3',5'-bisphosphate; 10 microM).
      Apamin inhibited PACAP relaxation. VIP and PACAP relaxation was blocked by 10
      U/ml alpha-chymotrypsin. L-NAME (-62.52 +/- 13.13%) and 1H-[1,2,4]oxadiazole-[4,3
      alpha]quinoxalin-1-one (ODQ; 10 microM, -67.67 +/- 6.80%) similarly inhibited
      electrical LES relaxation, and apamin blocked non-nitrergic relaxation. Nicotine
      relaxation (100 microM) was inhibited by L-NAME (-60.37 +/- 10.8%) and ODQ (
      41.90 +/- 7.89%), and apamin also blocked non-nitrergic relaxation. Non-nitrergic
      and apamin-sensitive LES relaxation by electrical stimulation or nicotine was
      strongly inhibited by MRS 2179, slightly inhibited by alpha-chymotrypsin and the
      P2X(1,2,3) receptor antagonist NF 279 (8,8 cent-[carbonylbis(imino-4,1
      phenylenecarbonylimino-4,1-phenylenecarbonylimino)]bis-1,3,5
      naphthalenetrisulfonic acid hexasodium salt; 10 microM), and unaffected by tin
      protoporphyrin IX (100 microM). Porcine LES relaxation after stimulation of
      intrinsic inhibitory motor neurons is mediated by two main neuromuscular
      pathways: nitric oxide through guanylate cyclase signaling and apamin-insensitive
      mechanisms and by non-nitrergic apamin-sensitive neurotransmission mainly
      mediated by ATP, ADP, or a related purine acting on P2Y1 receptors and a minor
      contribution of purinergic P2X1,2,3 receptors and PACAP. Nitrergic and purinergic
      co-transmitters show parallel effects of similar magnitude without major
      interplay. Our study shows no role for CGRP and only a minor one for VIP and
      carbon monoxide in porcine LES relaxation.

PMID- 16303919
TI  - Robust indices of clinical data: meaningless means.

PMID- 16303920
TI  - The ocular albinism type 1 (OA1) gene controls melanosome maturation and size.
AB  - PURPOSE: The authors took advantage of the Oa1 mutant mouse in combination with
      other albinism mouse models (i.e., Tyrosinase and membrane-associated transporter
      protein [Matp]) to study the function of Oa1, the gene mutated in ocular albinism
      type 1, in the RPE during development and after birth. METHODS: Enzyme activity
      and protein localization were analyzed by immunohistochemistry of tyrosinase
      (Tyr) in Oa1-null mice. Ultrastructural analysis and morphometry were performed
      by electron microscopy, of the RPE in Oa1-knockout mouse and double-mutant mice
      of Oa1 with either Tyr or Matp. RESULTS: Differently from other albinism models,
      Tyr activity was not impaired in Oa1-/- eyes. Hypopigmentation of the RPE in Oa1
      /- mice is due to a reduced number of melanosomes. Analysis of Oa1-/-;Tyr(c
      2J)/Tyr(c-2J) and Oa1-/-;Matp(uw)/Matp(uw) double-knockout mice, which display a
      block at stages II and III of melanosome maturation, respectively, revealed that
      Oa1 controls the rate of melanosome biogenesis at early stages of the
      organellogenesis, whereas the control on the organelle size is exerted at the
      final stage of melanosome development (stage IV). CONCLUSIONS: The findings
      indicate that Oa1 is involved in the regulation of melanosome maturation at two
      steps. Acting at early maturation stages, Oa1 controls the abundance of
      melanosomes in RPE cells. At later stages, Oa1 has a function in the maintenance
      of a correct melanosomal size. This study helps to define ocular albinism type 1
      as a defect in melanosome organellogenesis and not in melanin production.

PMID- 16303918
TI  - Superoxide dismutase mimetic preserves the glomerular capillary permeability
      barrier to protein.
AB  - Overproduction of superoxide (O2*) occurs in glomerular disease and may overwhelm
      the capacity of superoxide dismutase (SOD), thereby intensifying oxidant injury
      by O2* and related radical species that disrupt the glomerular capillary
      permeability barrier to protein. We examined the efficacy of the SOD mimetic
      tempol in preserving glomerular permeability to protein using 1) a rat model of
      glomerular immune injury induced by an antiglomerular basement membrane antibody
      (anti-GBM), and 2) isolated rat glomeruli in which injury was induced by the
      cytokine tumor necrosis factor-alpha (TNFalpha). To induce glomerular immune
      injury, rats received anti-GBM using a protocol that results in prominent
      infiltration of glomeruli by macrophages and in which macrophage-derived TNFalpha
      has been shown to mediate albuminuria. To increase glomerular capillary
      permeability to albumin (P(alb)) ex vivo, isolated glomeruli were incubated with
      TNFalpha at concentrations (0.5-4.0 microg/ml) known to stimulate O2* production.
      Increments in P(alb) were detected by measuring changes in glomerular volume in
      response to an applied oncotic gradient. Significant increases in the urine
      excretion of albumin and F(2alpha)-isoprostane were observed in rats with
      glomerular immune injury without a significant change in systolic blood pressure.
      Tempol treatment significantly reduced urine isoprostane and albumin excretion.
      In isolated glomeruli, TNFalpha increased P(alb) and tempol abrogated this
      effect, both in a dose-dependent manner. These observations indicate that SOD
      mimetics can preserve the glomerular permeability barrier to protein under
      conditions of oxidative stress from O2* production.

PMID- 16303921
TI  - In vitro targeting of NG2 antigen by 213Bi-9.2.27 alpha-immunoconjugate induces
      cytotoxicity in human uveal melanoma cells.
AB  - PURPOSE: To examine uveal melanoma cell lines for the expression of human
      melanoma proteoglycan (NG2) using monoclonal antibody (mAb) 9.2.27 and
      subsequently to assess the in vitro specificity and cytotoxicity of mAb 9.2.27
      conjugated to the alpha-particle-emitting radioisotope 213bismuth (213Bi-9.2.27)
      for uveal melanoma cells. METHODS: Immunocytochemistry and flow cytometry were
      used to examine OCM-1, OCM-3, OCM-8, OMM-1, Mel202 and 92-1 melanoma cell lines
      for NG2 expression. Melanoma cells were treated with test (213Bi-9.2.27) or
      control (213Bi-A2) alpha-immunoconjugates (AICs). The specific cytotoxicity of
      213Bi-9.2.27 AIC was evaluated using an MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfenyl)-2H-tetrazolium, inner salt) assay. Cell
      death was also assessed using TUNEL. RESULTS: OCM-1, OCM-8, OMM-1, and Mel202
      cells strongly expressed NG2. OCM-3 cells showed moderate expression and 92-1
      cells were NG2-negative. 213Bi-9.2.27 specifically killed NG2-positive OCM-1, OCM
      8, and OMM-1 cells in a concentration-dependent manner. D0 values for 37% cell
      survival of NG2-positive OCM-1, OCM-8, and OMM-1 cells were 5.8, 5.0, and 5.6
      microCi, respectively, and the value was 43.4 muCi for NG2-negative 92-1 cells.
      CONCLUSIONS: The specific cytotoxicity of 213Bi-9.2.27 AIC for NG2-positive, but
      not NG2-negative, cells suggests NG2 is a suitable target for alpha-immunotherapy
      in uveal melanoma. 213Bi-9.2.27 AIC used directly or as adjunct therapy may be a
      promising new agent for treating NG2-positive uveal melanomas or metastases.

PMID- 16303922
TI  - Receptors for the liver synthesized growth factors IGF-1 and HGF/SF in uveal
      melanoma: intercorrelation and prognostic implications.
AB  - PURPOSE: Uveal melanoma disseminates preferentially to the liver. The mechanism
      for this homing is largely unknown, but growth factors synthesized in the liver
      may be involved. The present study was undertaken to investigate the possible
      relationship between cell surface receptors for two such growth factors: the c
      Met proto-oncogene, which constitutes the receptor for hepatocyte growth
      factor/scatter factor (HGF/SF), and the insulin-like growth factor 1 receptor
      (IGF-1R). Their role as a prognostic factor was also clarified. METHODS: Paraffin
      embedded tumor specimens from 132 patients with primary uveal melanoma were
      analyzed by using well-established specific antibodies against c-Met and IGF-1R.
      The intercorrelation of receptor expression and association with melanoma-related
      survival of patients were determined by univariate and multivariate analyses.
      RESULTS: Whereas the expression of both IGF-1R and c-Met was significantly
      associated with melanoma-specific mortality by univariate analysis (P = 0.004 and
      P = 0.007, respectively) only IGF-1R showed independent prognostic value by
      multivariate analysis, P = 0.004. The prognostic value of IGF-1R was stronger
      than such currently used prognostic parameters as tumor cell type and tumor
      diameter (P = 0.021 and P = 0.026, respectively). The expression patterns of the
      two growth factors receptors were weakly intercorrelated. CONCLUSIONS: In
      conclusion, the data suggest that the receptors for IGF-1 and HGF/SF may play a
      role in the spread of uveal melanoma and its affinity to the liver. The strong
      correlation between IGF-1R expression and melanoma-specific mortality points to
      the use of IGF-1R as a prognostic tool.

PMID- 16303923
TI  - Characterization of ocular and metastatic uveal melanoma in an animal model.
AB  - PURPOSE: To characterize, in detail, tumor development, malignant cell
      dissemination, and metastasis in a 10-week animal model of uveal melanoma.
      METHODS: One million 92.1 human primary uveal melanoma cells were injected into
      the suprachoroidal space of the right eye of 27 immunosuppressed albino rabbits.
      Intraocular tumor growth was monitored weekly by fundoscopy and by
      ultrasonography at the end of the experiment. To document the progression of the
      disease, one animal per week was killed. The enucleated eyes, lungs, and livers
      were macroscopically examined and histopathologically studied by hematoxylin and
      eosin, periodic acid-Schiff, and immunohistochemistry. Mononuclear layers
      isolated from the rabbits' blood samples were cultured. RESULTS: Histopathology
      showed intraocular tumors in 89% of the animals. Tumor growth was found 1 week
      after cell inoculation, and by the end of the experiment large tumor masses were
      observed. Microscopic pulmonary metastatic foci were first observed 4 weeks after
      cell injection. By the end of the experiment, all the animals had metastasis to
      the lungs. Interestingly, 18% of the animals also had micrometastasis to the
      liver. Viable adherent uveal melanoma cells were successfully isolated from
      peripheral blood and grown in vitro. CONCLUSIONS: In this study, most rabbits
      developed intraocular tumors followed by lung metastasis, and some of these
      rabbits later developed liver micrometastases. This novel source of research
      material warrants a follow-up longer than 10 weeks to further explore the
      pathophysiologic bases of liver involvement commonly encountered in humans. The
      success in the isolation and culture of circulating malignant cells in this
      animal model suggests that it might be worthwhile to explore the application of
      this technique to the management of patients with primary uveal melanoma.

PMID- 16303924
TI  - Transscleral-RPE permeability of PEDF and ovalbumin proteins: implications for
      subconjunctival protein delivery.
AB  - PURPOSE: To investigate the in vitro, ex vivo, and in vivo transscleral-retinal
      pigment epithelium (RPE) permeability of PEDF and structurally related proteins
      for the exploration of novel routes of protein delivery to the retina. METHODS:
      Monkey RPE cells were cultured on permeable supports to separate apical and basal
      compartments. Porcine scleral tissue was placed in Ussing chambers to separate
      uveal and orbital compartments. Transepithelial resistance and voltage were
      measured by an electrical resistance system, and paracellular tracer flux was
      evaluated with trypan blue. Subconjunctival administration in rat eyes was by
      injections of soluble protein or by implantation of polyvinyl alcohol devices
      containing protein. Fluorescein-conjugated (Fl-) PEDF and ovalbumin were
      determined by spectrofluorometry, laser scanning, immunoblotting,
      epifluorescence, and confocal microscopy. Permeability was assessed by
      fluoresceinated-protein flux. RESULTS: Transepithelial resistance, impermeability
      to trypan blue, and confocal microscopy confirmed functional and structural tight
      junction formation of RPE cells cultured on permeable supports. Full-length Fl
      PEDF and Fl-ovalbumin proteins diffused through RPE cell monolayers from either
      the apical or basal side. Fl-ovalbumin diffused through scleral tissues at
      constant rates. Subconjunctival Fl-PEDF or Fl-ovalbumin administration in vivo
      revealed movement of full-length protein into the choroid and retina as early as
      1 hour. CONCLUSIONS: The sclera and RPE were permeable in vitro, ex vivo, and in
      vivo to PEDF and ovalbumin proteins. These large proteins can traverse through
      the sclera-RPE to reach the retina. In addition, these data prompt the proposal
      that subconjunctival protein delivery may represent a feasible and minimally
      invasive route for PEDF administration in the clinic.

PMID- 16303925
TI  - Reductions in serum vitamin A arrest accumulation of toxic retinal fluorophores:
      a potential therapy for treatment of lipofuscin-based retinal diseases.
AB  - PURPOSE: Excessive accumulation of lipofuscin is observed in numerous
      degenerative retinal diseases. A toxic vitamin A-based fluorophore (A2E) present
      within lipofuscin has been implicated in the death of RPE and photoreceptor
      cells. Here, we used an animal model that manifests accelerated lipofuscin
      accumulation (ABCA4-/- mutant) to evaluate the efficacy of a therapeutic approach
      based on reduction of serum retinol. METHODS: N-(4-hydroxyphenyl)retinamide (HPR)
      potently and reversibly reduces serum retinol. The interaction of HPR with
      retinol binding protein (RBP) and transthyretin was studied by spectrofluorometry
      and size-exclusion chromatography. To assess the effects of HPR on visual cycle
      retinoids and A2E biosynthesis, HPR was chronically administered to ABCA4-/-
      mice. Mice were evaluated using biochemical, electrophysiological, and
      morphologic techniques. RESULTS: Administration of HPR to ABCA4-/- mice caused
      immediate, dose-dependent reductions in serum retinol and RBP. Chronic
      administration produced commensurate reductions in visual cycle retinoids and
      arrested accumulation of A2E and lipofuscin autofluorescence in the RPE.
      Physiologically, HPR treatment caused modest delays in dark adaptation.
      Chromophore regeneration kinetics, light sensitivity of photoreceptors, and
      phototransduction processes were normal. Histologic examinations showed no
      alteration of retinal cytostructure or morphology. CONCLUSIONS: These findings
      demonstrate the vitamin A-dependent nature of A2E biosynthesis and validate a
      novel therapeutic approach with potential to halt the accumulation of lipofuscin
      fluorophores in the eye.

PMID- 16303926
TI  - Correlation of clinical and genetic findings in Hungarian patients with Stargardt
      disease.
AB  - PURPOSE: Autosomal recessive Stargardt disease (arSTGD) presents with substantial
      clinical and genetic heterogeneity. This study was conducted to correlate
      foveolar thickness (FT) and total macular volume (TMV), measured by optical
      coherence tomography (OCT), with other clinical characteristics and with specific
      genetic variation in Hungarian patients with arSTGD. METHODS: After a standard
      ophthalmic workup, both eyes of 35 patients with STGD from Hungary and of 25 age
      matched healthy control subjects were tested with OCT. FT and TMV were measured
      automatically with the OCT mapping software in the nine Early Treatment Diabetic
      Retinopathy Study areas of 3500 microm in diameter. All patients were screened
      for mutations by a combination of the ABCR400 microarray and direct sequencing.
      RESULTS: The patients with STGD presented with markedly thinned retina in the
      foveola and decreased macular volume, 72 microm and 1.69 mm3, respectively,
      compared with 169 microm and 2.48 mm3 in the normal subjects, respectively.
      Statistically significant correlation was observed between visual acuity (VA) and
      TMV and between VA and FT. Disease-associated mutations were detected in 23
      (65.7%) of 35 patients, including 48.5% with both alleles and 17.2% with one
      allele. The most frequent ABCA4 alleles in Hungarian patients with STGD were
      L541P/A1038V (in 28% of all patients), G1961E (20%) and IVS40+5G-->A (17%).
      Specific genotypes correlated with some phenotypic features and allowed for
      predictions of the disease progression. CONCLUSIONS: Hungarian patients with STGD
      presented with extensive foveolar thinning and macular volume loss. Genetic
      analysis detected several ABCA4 alleles at high frequency in the cohort of
      patients, suggesting founder effect(s). Unusually homogeneous distribution of
      disease-associated mutations aided genotype-phenotype correlation analyses in
      this population.

PMID- 16303927
TI  - Expression and activation of STAT3 in ischemia-induced retinopathy.
AB  - PURPOSE: Signal transducer and activator of transcription protein-3 (STAT3) is a
      transcription factor that participates in many biological processes, including
      tumor angiogenesis. The expression and activation of Stat3 in the mouse model of
      ischemia-induced retinal neovascularization was investigated to evaluate the
      possible role of STAT3 in retinal vascular disease. METHODS: Retinal
      neovascularization was induced in mice pups by exposure to hyperoxia. Gene
      microarrays were used to identify genes whose expression in the retina is altered
      at postnatal day (P)12 and P18. The relative levels of Stat3 mRNA were determined
      by semiquantitative RT-PCR. Stat3 protein levels and the levels of the activated
      form of Stat3 (pStat3) at P12, P15, P18, and P22 were determined by immunoblot
      analysis. Stat3 and pStat3 were demonstrated by immunofluorescence in retinal
      sections at P12, P15, and P18. RESULTS: In a series of microarray experiments,
      increased Stat3 mRNA levels in the retina were detected at P18. This result was
      validated by RT-PCR and demonstrated that Stat3 and pStat3 protein levels also
      increase during the development of neovascularization. Stat3 partially
      colocalized with blood vessels at the peak of neovascularization. pStat3
      colocalized completely with blood vessels in both experimental samples and age
      matched controls. pStat3 staining increased notably in the neovascular vessels at
      P15 and P18 and was more strongly associated with the epiretinal vessels than
      with inner retinal vessels. It was not detected in larger blood vessels, such as
      those of the optic nerve. CONCLUSIONS: The level of Stat3 expression increased,
      and pStat3 was observed in association with retinal neovascularization. Activated
      Stat3 was preferentially localized to neovascular retinal vessels. These data
      suggest that STAT3 may have a role in proliferative retinopathy.

PMID- 16303928
TI  - Opticin binds to heparan and chondroitin sulfate proteoglycans.
AB  - PURPOSE: The extracellular matrix glycoprotein opticin is a small leucine-rich
      repeat proteoglycan/protein family member that was discovered associated with
      vitreous humor collagen fibrils. Opticin is present throughout the vitreous, but
      is particularly concentrated at the internal limiting lamina, where it
      colocalizes with type XVIII collagen. The present study investigated whether
      opticin interacts directly with the heparan sulfate (HS) proteoglycan type XVIII
      collagen. METHODS: Solid-phase opticin binding assays were performed with
      immobilized type XVIII collagen and heparin albumin. Surface plasmon resonance
      (SPR) was used to investigate the binding of opticin to heparin and HS. RESULTS:
      Opticin bound to type XVIII collagen via its HS chains. SPR showed that opticin
      bound to porcine intestinal mucosa HS and heparin with moderately high affinity
      (K(D) 73 and 43 nM, respectively). Binding inhibition studies showed that
      hexasaccharides of heparin had a lower affinity for opticin than larger
      oligosaccharides; the sulfate groups of heparin contributed variably to opticin
      binding, with the group at ring position two of iduronate contributing least; and
      chondroitin sulfate A and B bound to opticin, whereas binding to chondroitin
      sulfate C and hyaluronan was not observed. CONCLUSIONS: Opticin binds to heparin,
      HS, chondroitin 4-sulfate, and dermatan sulfate, the binding affinity being
      dependent on sulfation pattern and oligosaccharide chain length. Opticin may
      provide a link between cortical vitreous collagen fibrils and the inner limiting
      lamina by binding HS proteoglycans and stabilize vitreous gel structure by
      binding chondroitin sulfate proteoglycans.

PMID- 16303929
TI  - Effect of stature and other anthropometric parameters on eye size and refraction
      in a population-based study of Australian children.
AB  - PURPOSE: To determine the effect of anthropometric parameters on refraction and
      ocular biometry. METHODS: Noncontact methods were used to examine ocular
      dimensions and cycloplegic refraction in a stratified random cluster sample of
      year-1 Sydney school students (mean age, 6 years; n = 1765). Height, body weight,
      and waist circumference were measured according to a standardized protocol. Body
      mass index (BMI) was subsequently calculated. The percentage of body fat was
      measured with leg-leg bioelectrical impedance analysis. Associations between
      parameters were analyzed by multiple linear regression. RESULTS: After adjustment
      for age in weeks, height was found to be strongly associated with axial length
      and corneal radius. Children in the 1st quintile for height had axial length of
      22.39 +/- 0.04 mm compared with 22.76 +/- 0.04 mm in children in the 5th
      quintile. Other anthropometric parameters were not associated with axial length
      or corneal radius. Height was not associated with anterior chamber depth after
      adjustment for weight. Increases in weight, BMI, and waist circumference were
      associated with a deeper anterior chamber after adjustment for height. No
      associations were found between the measured anthropometric parameters and
      refraction or axial length-corneal radius ratio. CONCLUSIONS: This study found a
      strong association between height and axial length and corneal radius, but not
      spherical equivalent refraction. The findings may demonstrate the effectiveness
      of emmetropization in the presence of normal physiological influences.

PMID- 16303931
TI  - Visual field defects and the risk of motor vehicle collisions among patients with
      glaucoma.
AB  - PURPOSE: To evaluate the association between visual field defects in the central
      24 degrees field and the risk of motor vehicle collisions (MVCs) among patients
      with glaucoma. METHODS: A nested case-control study was conducted in patients
      with glaucoma aged 55 or more. Cases were patients who were involved in a police
      reported motor vehicle collision (MVC) between January 1994 and June 2000;
      controls were those who had not experienced an MVC at the time of their
      selection. For each patient, an Advanced Glaucoma Intervention Study (AGIS) score
      was calculated on automated visual fields collected with the 24-2 or 3-2
      programs. RESULTS: With respect to the better-eye AGIS score, compared with
      patients with no visual field defect, those with severe defects (scores 12-20)
      had an increased risk of an MVC (odds ratio [OR] 3.2, 95% CI 0.9-10.4), although
      the association was not statistically significant. Moderate (6-11) or minor field
      defects (1-5) in the better eye were not associated with the risk of involvement
      in a crash. In the worse eye, patients with moderate or severe field defects were
      at significantly increased risk of an MVC (OR 3.6, 95% CI 1.4-9.4 and OR 4.4, 95%
      CI 1.6-12.4, respectively) compared with those with no defects. Minor field
      defects in the worse eye did not increase risk of MVC (OR 1.3, 95% CI 0.5-3.4).
      CONCLUSIONS: Patients with glaucoma who have moderate or severe visual field
      impairment in the central 24 degrees radius field in the worse-functioning eye
      are at increased risk of involvement in a vehicle crash.

PMID- 16303930
TI  - Heritability of macular pigment: a twin study.
AB  - PURPOSE: Several studies have reported higher levels of macular pigment (MP) in
      association with reduced risk for age-related macular degeneration (ARMD), a
      disease to which there is a genetic predisposition. A classic twin study was
      performed to determine the heritability of MP in the healthy eye. METHODS: One
      hundred fifty twin pairs (76 monozygotic [MZ] and 74 dizygotic [DZ]), aged 18 to
      50 years, participated. MP optical density was measured psychophysically with
      heterochromatic flicker photometry (HFP) and also with an imaging method
      involving fundus autofluorescence (AF). The covariance of MP within MZ and DZ
      twin pairs was compared, and genetic modeling techniques were used to determine
      the relative contributions of genes and environment to the variation in MP.
      RESULTS: The mean MP optical density, measured using HFP, was 0.43 +/- 0.21.
      Using AF, the mean MP optical density, measured at 1 degrees eccentricity, was
      0.28 +/- 0.11. MP optical densities correlated more highly in MZ twins than in DZ
      twins, according to both HFP (MZ: 0.65; DZ: 0.24) and AF (MZ: 0.83; DZ: 0.50). A
      model combining additive genetic and unique environmental effects provided the
      best fit and resulted in MP heritability estimates of 0.67 (95% CI, 0.52-0.77)
      and 0.85 (95% CI, 0.78-0.90) for HFP and AF readings, respectively. CONCLUSIONS:
      This classic twin study demonstrates that genetic background is an important
      determinant of MP optical density, reflected in heritability estimates of 0.67
      and 0.85 for HFP and AF measures, respectively.

PMID- 16303933
TI  - Refractive error, ocular biometry, and lens opalescence in an adult population:
      the Los Angeles Latino Eye Study.
AB  - PURPOSE: To characterize age- and gender-related differences in refractive error,
      ocular biometry, and lens opalescence (NOP) in a population-based sample of adult
      Latinos. Also assessed were the determinants of age-related refractive
      differences. METHODS: Participants in the Los Angeles Latino Eye Study (LALES), a
      population-based study of Latinos aged 40 years and more, underwent an ophthalmic
      examination, including ultrasonic measurements of axial length (AL), vitreous
      chamber depth (VCD), anterior chamber depth (ACD), lens thickness (LT), and
      noncycloplegic automated and subjective refraction. Corneal curvature/power (CP)
      was measured using an autorefractor. NOP was graded at the slit lamp by an
      ophthalmologist using the Lens Opacity Classification System II. Age- and gender
      related differences were calculated. Multiple regression models were used to
      identify the determinants of age-related refractive differences. RESULTS: Of the
      6357 LALES participants, 5588 phakic individuals with biometric data were
      included in this analysis. Older individuals had shallower ACDs, thicker lenses,
      more NOP, and more hyperopia compared to younger individuals (P < 0.001). There
      was no age-related difference in AL (P > or = 0.05). Women had significantly
      shorter AL, shallower ACD and VCD, than did men (P < or = 0.01). The strongest
      determinants of refractive error were AL (primarily VCD) and CP. NOP was a small
      but significant determinant of refractive error in older individuals.
      CONCLUSIONS: Age- and gender-related differences in ocular biometric, refractive
      error, and NOP measurements are present in adult Latinos. While the relative
      contribution of NOP in determining refractive error is small, it is greater in
      older persons compared to younger individuals.

PMID- 16303934
TI  - Prevalence of open-angle glaucoma in a rural south Indian population.
AB  - PURPOSE: To determine the prevalence of primary open-angle glaucoma (POAG) and
      the associated risk factors in a rural population in southern India. METHODS:
      Subjects aged 40 years or more (n = 3934) underwent a complete ophthalmic
      examination. Glaucoma was diagnosed according to the International Society of
      Geographical and Epidemiologic Ophthalmology classification. RESULTS: Complete
      data were available for 3924 subjects (response rate, 81.75%). In eyes with
      normal suprathreshold visual fields, the mean intraocular pressure was 14.29 +/-
      3.32 mm Hg (97.5th and 99.5th percentiles, 21 and 25 mm Hg, respectively). The
      mean vertical cup-to-disc ratio was 0.39 +/- 0.17 (97.5th and 99.5th percentiles,
      0.7 and 0.8, respectively). Sixty-four subjects had definite POAG (1.62%, 9.5% CI
      1.42-1.82); 30 were men and 34 were women. Subjects with POAG (59.85 +/- 10.43
      years) were older (P < 0.001) than the study population (53.78 +/- 10.71 years).
      In only one (1.5%) person was POAG diagnosed before the study. Two (3.12%)
      subjects were blind due to POAG; 21 (32.81%) subjects had a presenting IOP >21 mm
      Hg, and 43 (67.19%) had an IOP <21 mm Hg. The mean central corneal thickness in
      subjects with POAG (502.82 +/- 35.29 microm) was not different from that of the
      normal study population (505.93 +/- 31.11 microm). No association was found with
      diabetes mellitus, systemic hypertension, gender, and myopia. Increasing IOP (per
      mm Hg) was associated with the disease (OR 1.12; 95% CI, 1.08-1.16). The odds for
      POAG increased with advancing age after adjustment for gender. CONCLUSIONS: The
      prevalence of POAG in this population was 1.62%. The prevalence increased with
      age, and 98.5% were not aware of the disease.

PMID- 16303932
TI  - Risk factors for age-related macular degeneration: findings from the Andhra
      Pradesh eye disease study in South India.
AB  - PURPOSE: To assess prevalence, potential risk factors, and population
      attributable risk percentage (PAR%) for age-related macular degeneration (AMD) in
      the Indian state of Andhra Pradesh. METHODS: A population-based study, using a
      stratified, random, cluster, systematic sampling strategy, was conducted in the
      state of Andhra Pradesh in India from 1996 to 2000. Participants from 94 clusters
      in one urban and three rural areas representative of the population of Andhra
      Pradesh underwent a detailed interview and a detailed dilated ocular evaluation
      by trained professionals. In this report, the authors present the prevalence
      estimates of AMD and examine the association of AMD with potential risk factors
      in persons aged 40 to 102 years (n = 3723). AMD was defined according to the
      international classification and grading system. Standard bivariate and
      multivariate analyses were performed to identify the potential risk factors for
      AMD. PAR% was calculated by Levin's formula. RESULTS: AMD was present in 71
      subjects--an age-gender-area-adjusted prevalence of 1.82% (95% confidence
      interval [CI], 1.39%-2.25%). Risk factors that were significant in bivariate
      analyses were considered for multivariate logistic regression analysis.
      Multivariate analysis showed that the adjusted prevalence of AMD was
      significantly higher in those 60 years of age or older (odds ratio [OR], 3.55;
      95% CI, 1.61-7.82) and history of prior cigar smoking (OR, 3.29; 95%CI, 1.42
      7.57). Presence of cortical cataract and prior cataract surgery were
      significantly associated with increased prevalence of AMD (adjusted OR, 2.87; 95%
      CI, 1.57-5.26 and 3.79; 95% CI, 2.1-6.78), respectively. The prevalence of AMD
      was significantly lower in light alcohol drinkers (adjusted OR, 0.38; 95% CI,
      0.19-0.76) compared with nondrinkers. The PAR% for hypertension and heavy cigar
      smoking was 10% and 14%, respectively, in this population. CONCLUSIONS: The
      prevalence of AMD in this south Indian population is similar to those reported in
      other developed countries. Abstinence from smoking may reduce the risk of AMD in
      this population.

PMID- 16303937
TI  - Posterior polymorphous corneal dystrophy in Czech families maps to chromosome 20
      and excludes the VSX1 gene.
AB  - PURPOSE: Posterior polymorphous corneal dystrophy (PPCD) is an autosomal dominant
      disorder, affecting both the corneal endothelium and Descemet's membrane. In the
      Czech Republic, PPCD is one of the most prevalent corneal dystrophies. The
      purpose of this study was to determine the chromosomal locus of PPCD in two large
      Czech families, by using linkage analysis. METHODS: Linkage analysis was
      performed on 52 members of two Czech families with PPCD and polymorphic
      microsatellite markers and lod scores were calculated. The candidate gene VSX1
      was also screened for mutations. RESULTS: Significant lod scores were obtained
      with microsatellite markers on chromosome 20. Linkage analysis delineated the
      Czech PPCD locus to a 2.7-cM locus on chromosome 20, region p11.2, between
      flanking markers D20S48 and D20S139, which excluded VSX1 as the disease-causing
      gene in both families. In addition, the exclusion of VSX1 was confirmed by
      sequence analysis. CONCLUSIONS: This study reports the localization of PPCD in
      patients of Czech origin to chromosome 20 at p11.2. Linkage data and sequence
      analysis exclude VSX1 as causative of PPCD in two Czech families. This refined
      locus for PPCD overlaps the congenital hereditary endothelial dystrophy (CHED1)
      disease interval, and it is possible that these corneal dystrophies are allelic.

PMID- 16303935
TI  - Postblink changes in the ocular modulation transfer function measured by a double
      pass method.
AB  - PURPOSE: To examine the temporal changes in the modulation transfer function
      (MTF) of the eye after a blink. METHODS: The distance MTF of a 5-mm pupil was
      derived from double-pass retinal images in 20 healthy young subjects at various
      intervals after a blink (1 second up to 15 seconds). Such measurements include
      the effects of wavefront aberration, scattered light, and errors in focus and are
      thus more relevant to real life than are estimates of MTF based on wavefront
      errors alone. RESULTS: Optimal MTF by a variety of criteria was found some 6
      seconds after a blink. CONCLUSIONS: Inclusion of the effects of stray light and
      errors of focus does not affect the finding that optimal retinal image quality
      occurs some time after a blink. It does not appear that a loss in optical quality
      is the trigger of normal blinking.

PMID- 16303936
TI  - Systemic omega-6 essential fatty acid treatment and pge1 tear content in
      Sjogren's syndrome patients.
AB  - PURPOSE: To determine the effect of oral omega-6 essential fatty acids on PGE(1)
      tear content and signs and symptoms of ocular discomfort in patients with
      Sjogren's syndrome (SS). METHODS: This randomized, double-masked, controlled,
      clinical trial involved 40 patients with primary SS, divided into two groups:
      group 1: 20 patients (18 women, 2 men; mean age, 36.9 +/- 7.9 years [SD]) treated
      for 1 month with linoleic acid (LA; 112 mg), and gamma-linolenic acid (GLA; 15
      mg) administered twice daily; group 2: 20 patients (19 women, 1 man; mean age,
      36.3 +/- 5.5 years) treated twice daily with placebo. Patients underwent three
      examinations: at baseline (T0), after 1 month of treatment (T1), and 15 days
      after suspension of treatment (T2). At each examination, the following tests were
      performed: tear sampling (2 microL) from the inferior meniscus, tear break-up
      time (BUT), fluorescein stain of the ocular surface, and tear basal secretion. A
      symptom score was also obtained at each examination. PGE1 was evaluated by enzyme
      immunoassay. The primary efficacy variable was PGE1 content of tears. RESULTS:
      The tear PGE1 levels were significantly increased in group 1 at T1 versus T0
      (PGE1 level: T0, 44 +/- 5.4 ng/mL; T1, 58.3 +/- 5.5 ng/mL; P < 0.01 versus T0 and
      group 2 at T1). At examination T2, a statistically significant reduction of PGE1
      levels toward baseline was observed (45.7 +/- 5.2 ng/mL; P < 0.01 versus T1). A
      statistically significant reduction of symptom score was observed in group 1 at
      examination T1 (P < 0.01 versus T0 and group 2 score). At examination T2, the
      symptom score was significantly higher than T1 but remained lower than T0. The
      corneal fluorescein stain in group 1 showed a statistically significant
      improvement at examination T1 versus T0 and group 2 (P < 0.01). This improvement
      was also present at T2 (P < 0.02). No statistically significant differences were
      found for the other tests. No statistically significant changes were observed in
      the patients in group 2 at all examination time points. CONCLUSIONS: Omega-6
      administration increases the PGE1 levels in tears of patients with SS and
      improves ocular surface signs and symptoms of ocular discomfort.

PMID- 16303938
TI  - Mapping of the normal human corneal sub-Basal nerve plexus by in vivo laser
      scanning confocal microscopy.
AB  - PURPOSE: To produce a two-dimensional reconstruction map of the living human sub
      basal corneal nerve plexus using in vivo confocal microscopy. METHODS: Laser
      scanning in vivo confocal microscopy was performed on three normal eyes of three
      healthy human subjects. Subjects were asked to fixate on targets arranged in a
      grid to enable examination of the cornea in a wide range of positions. Using the
      section mode, a mean of 573 +/- 176 images of the sub-basal plexus were obtained
      for each subject. The data were arranged and images were mapped for each subject
      into confluent montages. RESULTS: Mean dimensions of the corneal areas mapped
      were 4.95 +/- 0.53 mm horizontally and 5.14 +/- 0.53 mm vertically. In all
      subjects, the sub-basal nerve plexus appeared to radiate toward a whorl-like
      complex centered 1 to 2 mm inferior to the corneal apex. Outside this area, the
      nerve fiber bundles in the remainder of the cornea were arranged in a radiating
      pattern. Mean nerve density was significantly higher in the inferocentral whorl
      region (25,249 +/- 616 microm/mm2) compared with the central cornea (21,668 +/-
      1411 microm/mm2) (Mann-Whitney U test; P = 0.05). CONCLUSIONS: This is the first
      study to elucidate the overall distribution of sub-basal nerves in the healthy,
      live central to mid-peripheral human cornea by laser scanning in vivo confocal
      microscopy. The whorl pattern of the sub-basal nerves is similar to that seen in
      the epithelium in corneal verticillata and may lend support to the theory that
      epithelial cells and nerves migrate centripetally in tandem.

PMID- 16303941
TI  - Fuchs corneal dystrophy: aberrant collagen distribution in an L450W mutant of the
      COL8A2 gene.
AB  - PURPOSE: To characterize histologically Descemet's membrane in an early-onset
      Fuchs corneal dystrophy (FCD) COL8A2 mutant and compare these findings with
      corneas from late-onset FCD and normal corneas. METHODS: A corneal explant from a
      patient with the L450W COL8A2 mutation and others with late-onset disease were
      studied with antibodies to collagens IV, VIIIA1, VIIIA2, fibronectin, and
      laminin. Transmission electron microscopy was performed on a portion of the
      explant. Control explants included eye bank corneas without known disease and
      surgical explants from unrelated conditions. RESULTS: In normal corneas, a
      regular array of colocalized COL8A1 and COL8A2 was observed in the anterior half
      of Descemet's membrane. In the L450W mutant, Descemet's membrane was several
      times thicker than normal and traversed by refractile strands and blebs that
      stained intensely for COL8A2, a feature also observed in late-onset FCD. Both the
      alpha1 and alpha2 subtypes of collagen VIII were observed at high levels along
      the anterior edge of Descemet's, another abnormal feature also found in late
      onset FCD. Ultrastructure of the L450W cornea revealed a well-formed anterior
      banded layer more than three times thicker than normal. An unusual, thin internal
      layer was rich in patches of wide-spaced collagen. The layer is a distinctive
      pathologic structure that is associated with FCD and is characterized by
      approximately 120 nm periodicity and the presence of collagen VIII. Depositions
      of collagen IV, fibronectin, and laminin were also greatly increased in the of
      posterior Descemet's membrane, yet another general feature shared between early-
      and late-onset disease. CONCLUSIONS: Early-onset COL8A2 L450W disease involves
      massive accumulation and abnormal assembly of collagen VIII within Descemet's
      membrane, a process that is presumed to begin during fetal development. Both
      early- and late-onset subtypes of FCD appear to be the result of abnormal
      basement membrane assembly rather than a primary defect in endothelial
      metabolism.

PMID- 16303939
TI  - Distinct populations of dendritic cells in the normal human donor corneal
      epithelium.
AB  - PURPOSE: To characterize dendritic cells (DC) in normal human corneal epithelium.
      METHODS: Normal human donor corneal epithelium was examined by fluorescence
      microscopy with single and double staining for multiple markers. Morphologic
      studies were also performed by confocal microscopy. HLA-DRa, CD1c, and CD16 mRNA
      expression in the corneal epithelium was examined by RT-PCR. CD45+ cells were
      separated from the corneal epithelium with magnetic beads and then were
      stimulated with TNF-alpha and lipopolysaccharide in vitro. RESULTS: CD45+ cells
      were mainly located in the basal-cell layer of the corneal epithelium and partly
      in the wing/surface layers. CD45-positive cell numbers were significantly higher
      in the peripheral cornea (3-6 mm from the center) than in the central cornea (0-3
      mm from the center). All these cells expressed HLA-DR and CD11c but not CD3,
      CD11b, CD14, CD19, CD56, or CD66, suggesting that these were bone marrow-derived
      myeloid DC. Some DR+CD11c+ DCs from the periphery expressed CD1c and CD16. HLA
      DRa, CD1c, and CD16 mRNAs were detected in normal corneal epithelium. These
      CD11c+ DCs did not express CD123, CD1a, DC marker (CMRF56), CD40, CD80, or CD86.
      When CD45+ cells were isolated from the corneal epithelium by magnetic cell
      sorting, CD40 and CD86 expression were detected after in vitro stimulation with
      TNF-alpha and lipopolysaccharide. CONCLUSIONS: These findings demonstrate that
      normal human corneal epithelium contains at least three DC phenotypes, with HLA
      DR+ myeloid lineage CD11c+CD16- DCs as the main population plus a small number of
      CD11c+CD16+ DCs and CD11c+CD1c+ DCs. These cells can be discriminated from bone
      marrow-derived cells in the human corneal stroma.

PMID- 16303940
TI  - Regulatory role of FGF-2 on type I collagen expression during endothelial
      mesenchymal transformation.
AB  - PURPOSE: To investigate the regulatory role of FGF-2 on type I collagen
      expression during endothelial mesenchymal transformation (EMT). METHODS: Corneal
      endothelial cells (CECs) treated with FGF-2 from the primary culture to the third
      passage were transformed and designated as fibroblastic CECs (fCECs). Steady
      state levels of both type I collagen RNAs were measured using reverse
      transcription-real-time PCR, and their half lives were determined in the presence
      of inhibitor of RNA synthesis. Limited proteolysis with pepsin was used to
      determine secretion of type I collagen. Protein-protein interaction was
      determined by coimmunoprecipitation, and subcellular localization was studied by
      immunofluorescence. RESULTS: fCECs were characterized by greatly stimulated
      proliferative potential, loss of contact inhibition, and multilayer fibroblastic
      cells. The steady state level of alpha1(I) collagen RNA was greatly upregulated
      through stabilization of the message in fCECs, whereas steady state level and
      half-life of the alpha2(I) collagen RNA were slightly increased compared with the
      corresponding levels in normal CECs. Of interest, fCECs predominantly secreted
      homotrimeric type I collagen, [alpha1(I)](3), with heterotrimeric type I collagen
      as a minor species. Type I collagen in fCECs was preferentially associated and
      colocalized with Hsp47 at Golgi apparatus as opposed to its association with
      protein disulfide isomerase in CECs. LY294002 (a specific PI 3-kinase inhibitor)
      greatly reduced the steady state levels and stability of alpha1(I) and alpha2(I)
      collagen RNAs and the secretion of type I collagen. CONCLUSIONS: FGF-2 directly
      mediates corneal EMT through the action of PI 3-kinase, which acts on
      posttranscriptional regulation by affecting the stability of type I collagen RNA.

PMID- 16303943
TI  - Donor fibroblast chimerism in the pathogenic fibrotic lesion of human chronic
      graft-versus-host disease.
AB  - PURPOSE: Tissue atrophy and excessive fibrosis are prominent histologic features
      of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem
      cell transplantation, but the underlying mechanism remains unknown. The current
      study was undertaken to investigate whether the increase in fibroblasts at the
      site of pathogenic fibrosis originated from transplanted donor cells in patients
      with chronic GVHD. METHODS: Lacrimal gland biopsy specimens were obtained from
      nine patients with chronic GVHD. The male-specific sequences detected by
      fluorescein in situ hybridization (FISH) and in situ hybridization (ISH) were
      used as markers for the donor cells in seven female patients who had received a
      transplant from male donors. Primary fibroblast cultures were generated from
      lacrimal gland biopsy specimens and examined for mismatched genetic markers
      between recipients and donors. RESULTS: In lacrimal gland specimens obtained from
      seven female patients who received a sex-mismatched transplant, 13.4% to 26.7% of
      CD34+ fibroblasts that accumulated in the fibrotic lesion were donor derived, as
      determined by FISH for the Y-chromosome. The male-specific mRNA was also detected
      in the lacrimal gland fibroblasts by ISH. Primary lacrimal gland fibroblast
      cultures were generated from four patients with chronic GVHD and further examined
      for mismatched genetic markers between recipients and donors. As a result, the
      presence of donor origin of the fibroblasts was demonstrated by detecting the Y
      chromosome sequence and donor-specific microsatellite genetic markers.
      CONCLUSIONS: These findings together indicate the chimeric status of accumulated
      CD34+ fibroblasts in the lacrimal gland of patients with chronic GVHD.
      Fibroblasts originating from circulating donor-derived precursors may participate
      in the excessive fibrosis in these patients.

PMID- 16303944
TI  - The heterogeneous murine corneal stromal cell populations in vitro.
AB  - PURPOSE: To demonstrate that the murine corneal stroma is inhabited by
      heterogeneous cell populations that include cells expressing nestin. METHODS:
      Collagenase-isolated corneal stroma cells obtained from newborn and adult mice
      (2nd and 12th postnatal weeks, respectively), were seeded at low (5 cells/mm2),
      intermediate (50 cells/mm2), and high (500 cells/mm2) densities in DMEM/F12
      containing insulin, transferrin, selenium, and 1% nonessential amino acids.
      Corneal stroma cells cultured at 500 cells/mm2 were treated with 10 ng/mL human
      recombinant transforming growth factor (TGF)-beta1 for 5 days. Cell morphology
      and expression of alpha-smooth muscle actin, choline acetyltransferase, CD45,
      glial fibrillary acidic protein (GFAP), keratocan, nestin, neurofilaments,
      protein gene product 9.5, tyrosine hydroxylase, and vimentin were examined.
      RESULTS: Phase-contrast microscopy demonstrated that freshly isolated corneal
      stromal cells are heterogeneous in morphology and include dendritic, stellate,
      neuronal, and small polyhedral cells. Immunostaining of primary cultures of 2-
      and 12-week-old mice, 24 hours after seeding at the intermediate density, showed
      that 100% of cells expressed vimentin and 97.7% +/- 2.7% expressed keratocan.
      alpha-Smooth muscle actin was expressed by 0.2% +/- 0.05% of cells in the 2-week
      old group and 0.1% +/- 0.07% in 12-week-old group. Neurofilament was expressed by
      0.5% +/- 0.03% and 0.7% +/- 0.03% of cells in the 2- and 12-week-old groups,
      respectively. No cell expressed GFAP or nestin. After 5 days in culture, cells
      seeded at high density aggregated as clusters that were immunoreactive to nestin
      in both groups. Cell clusters and migrating cells reacted to pgp 9.5, and
      migrating cells, but not the cell clusters, reacted to tyrosine hydroxylase. Cell
      cluster formation and nestin expression were abolished by culturing in the
      presence of TGF-beta1. CONCLUSIONS: Normal murine corneal stroma contains
      heterogeneous cell populations including cells with the potential to form
      clusters and express the progenitor marker nestin. This potential is disrupted by
      the addition of TGF-beta1 to the culture medium.

PMID- 16303942
TI  - The implications of the upregulation of ICAM-1/VCAM-1 expression of corneal
      fibroblasts on the pathogenesis of allergic keratopathy.
AB  - OBJECTIVE: The present study investigated the expression of ICAM-1 and VCAM-1 on
      fibroblasts with interleukin (IL)-4 and/or tumor necrosis factor (TNF)-alpha
      stimulation and assessed the effect of eosinophil adhesion on fibroblast
      viability. METHODS: Primary cultured human corneal fibroblasts were incubated
      with IL-4, TNF-alpha, or their combination for 24 hours. Expression of ICAM-1 and
      VCAM-1 was examined by real-time quantitative PCR and flow cytometric analysis.
      Purified eosinophils were cocultured with activated fibroblasts, and the number
      of eosinophils adhered to fibroblasts and the number of damaged fibroblasts were
      counted using microscopy. In a separate trial, conjunctival and corneal
      impression cytology was performed on patients with atopic keratoconjunctivitis
      and corneal ulcers (eight eyes) to assess the status of the ocular surface
      epithelium and the presence of inflammatory cell infiltrates. RESULTS: Real-time
      quantitative PCR and flow cytometric analysis revealed that both mRNA and protein
      of VCAM-1 and ICAM-1 were upregulated by IL-4 and TNF-alpha. IL-5-primed
      eosinophils adhered to the corneal fibroblasts treated with IL-4 and TNF-alpha,
      and the fibroblasts were damaged by eosinophil adherence. Anti-ICAM-1 antibody
      and anti-VCAM-1 antibody inhibited the eosinophil adherence to fibroblasts and
      the fibroblast damage. Impression cytology revealed extensive infiltration of
      neutrophil and eosinophils among isolated ocular surface epithelial cells with
      advanced squamous metaplasia. CONCLUSIONS: Corneal fibroblasts expressed ICAM-1
      and VCAM-1 when activated with IL-4 and TNF-alpha. Eosinophils can adhere to the
      activated fibroblasts and can induce subsequent fibroblast damage through these
      adhesion molecules. Eosinophil adhesion to fibroblasts may possibly contribute to
      the pathogenesis of severe persistent allergic corneal ulcers.

PMID- 16303945
TI  - Novel expression and characterization of lymphatic vessel endothelial hyaluronate
      receptor 1 (LYVE-1) by conjunctival cells.
AB  - PURPOSE: Lymphatic vessel endothelial hyaluronic acid receptor (LYVE-1) is a
      newly discovered lymphatic-specific marker. To date, there is no report of its
      expression on conjunctival cells. The purpose of this study was to investigate
      the expression of LYVE-1 in normal conjunctiva, to phenotype LYVE-1+ cells, and
      to study changes in their expression levels during corneal inflammation. METHODS:
      Flat-mounted conjunctivae or cross sections of eyeballs were harvested from
      BALB/c mice (6-8 weeks of age) for immunofluorescent confocal microscopic
      studies. RESULTS: The data demonstrate, for the first time, that in addition to
      its expression on lymphatic vessels, LYVE-1 was expressed on CD45+, CD11b+, and
      CD31- conjunctival cells, indicating a bone-marrow-derived monocytic lineage.
      Surprisingly, the number of cells that expressed LYVE-1 decreased during corneal
      inflammation, in conjunction with ingrowth of lymphatics into the cornea.
      CONCLUSIONS: A new population of monocytic cells has been found to express LYVE-1
      in normal conjunctiva. These cells that normally express LYVE-1 may act as a
      reservoir for lymphangiogenesis and cell recruitment when the immune system is
      challenged.

PMID- 16303946
TI  - Mitochondria are fast Ca2+ sinks in rat extraocular muscles: a novel regulatory
      influence on contractile function and metabolism.
AB  - PURPOSE: The ultrafast extraocular muscles necessitate tight regulation of free
      cytosolic Ca2+ concentration ([Ca2+]i). Mitochondrial Ca2+ influx may be fast
      enough for this role. In the present study, three hypotheses were tested: (1)
      Mitochondrial Ca2+ uptake regulates [Ca2+]i and production of force in
      extraocular muscle; (2) mitochondrial content correlates with their use as Ca2+
      sinks; and (3) mitochondrial content in extraocular muscle is determined by the
      transcription factors and coactivators that initiate muscle adaptation to aerobic
      exercise. METHODS: Extraocular and extensor digitorum longus (EDL) muscles from
      adult Sprague-Dawley rats were used to examine how the Ca2+ release agonists
      caffeine and 4-chloro-3-ethylphenol (CEP), calcimycin (a Ca2+ ionophore) and
      carbonyl cyanide m-chlorophenyl hydrazone (CCCP; a mitochondrial uncoupler) alter
      [Ca2+]i and force transients. Mitochondrial volume density and capillary density
      were analyzed by stereology and citrate synthase and cytochrome c oxidase by
      biochemical assays. Real-time PCR measured mRNAs of genes involved in
      mitochondrial biogenesis. RESULTS: Caffeine, CEP, and calcimycin increased
      resting [Ca2+]i to a greater extent in EDL. Peak tetanic [Ca2+]i increased in
      extraocular muscle with caffeine and CEP. CCCP augmented peak tetanic and
      submaximum [Ca2+]i and force significantly more in extraocular muscles.
      Mitochondrial volume density and capillary density were three times greater, and
      citrate synthase and cytochrome c oxidase were only approximately 2-fold higher
      in extraocular muscle. Calcineurin Aalpha, calcineurin B, and peroxisome
      proliferator activated receptor (PPAR)gamma were more abundant in extraocular
      muscle. CONCLUSIONS: These data support the hypothesis that mitochondria serve as
      Ca2+ sinks in extraocular muscles. The high mitochondrial content of these
      muscles may partly reflect this additional function. It is likely that
      mitochondrial Ca2+ influx increases the dynamic response range of the extraocular
      muscles and matches metabolic demand to supply.

PMID- 16303949
TI  - Measurement of position acuity in strabismus and amblyopia: specificity of the
      vernier VEP paradigm.
AB  - PURPOSE: An objective measure of positional acuity is desirable in the nonverbal
      clinical population. This study was conducted to investigate the specificity of
      the vernier VEP as a measure of positional acuity, evaluating the potential
      confound of asymmetric motion responses that may be present in some groups of
      patients. These motion responses could masquerade as position-specific responses,
      since they occur at the same response frequency as the vernier-related response.
      METHODS: Twelve observers with early-onset esotropia (EOE), 30 children with
      untreated amblyopia, and 15 control children underwent swept vernier VEP acuity
      testing accompanied by a swept motion control stimulus. The control condition was
      used to detect the presence of artifactual responses not related to position
      sensitivity. The patients with EOE were selected for high levels of motion
      asymmetry as documented with oscillating gratings presented monocularly. As a
      measure of motion confound (penetration), the proportion of first-harmonic
      responses recorded in the control condition was determined. RESULTS: The
      penetration rate in the vernier condition in each study group (EOE: 0.93%;
      amblyopes: 4.26%; normal subjects: 2.40%) and the entire group (2.85%) was
      acceptably low. The level of penetration was not significantly influenced by the
      presence of amblyopia. CONCLUSIONS: The vernier VEP paradigm, when applied in the
      manner described, can be interpreted as a measure of position sensitivity. The
      presence of motion asymmetry or untreated amblyopia does not affect the validity
      of vernier measurements made.

PMID- 16303947
TI  - Palisade endings in extraocular muscles of the monkey are immunoreactive for
      choline acetyltransferase and vesicular acetylcholine transporter.
AB  - PURPOSE: To analyze palisade endings in extraocular muscles (EOMs) of a primate
      species and to examine our previous findings in cat that palisade endings are
      putative effector organs. METHODS: Eleven monkeys (Macaca fascicularis) of both
      sexes, between 4 and 6 years of age were analyzed. Whole EOM myotendons were
      immunostained with four combinations of triple-fluorescent labeling and examined
      by confocal laser scanning microscopy. Labeling included antibodies against
      choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT),
      neurofilament, and synaptophysin. Muscle fibers were counterstained with
      phalloidin. RESULTS: Palisade endings were observed in all monkey EOMs. Nerve
      fibers extended from the muscle into the tendon and looped back to divide into a
      terminal arborization (palisade ending) around a single muscle fiber tip. In
      approximately 30% of the cases, nerve fibers supplying palisade endings often
      established motor terminals outside the palisade complex. Nerve fibers forming
      palisade endings were ChAT-neurofilament positive. Axonal branches of palisade
      endings were ChAT-neurofilament positive as well. All palisade nerve terminals
      exhibited ChAT-synaptophysin immunoreactivity. Within the palisade complex,
      palisade nerve terminals exhibited VAChT immunoreactivity. All palisade nerve
      terminals were VAChT-synaptophysin immunoreactive. CONCLUSIONS: The results
      confirm that in the monkey, palisade endings contain acetylcholine and are
      therefore most likely effector organs. Palisade endings are also present in human
      EOMs and because of their location at the myotendinous junction, these organs are
      of crucial interest for strabismus surgery.

PMID- 16303948
TI  - Eliminating the Ant1 isoform produces a mouse with CPEO pathology but normal
      ocular motility.
AB  - PURPOSE: The adenine nucleotide transporter 1 gene (ANT1) encodes an inner
      mitochondrial membrane protein that transports ATP into the cell. Mutations
      within ANT1 produce a syndrome of chronic progressive external ophthalmoplegia
      (CPEO) in humans. Ant1 knockout (Ant1-/-) mice develop cardiomyopathy and
      mitochondrial myopathy of limb muscles. Because the extraocular muscles (EOM) are
      preferentially affected in human CPEO, the objective of this study was to
      determine whether Ant1-/- mice also exhibit an EOM mitochondrial myopathy.
      METHODS: ANT isoform expression of isolated EOMs, EOM morphology and
      mitochondrial content, mitochondrial structure and function, ocular motility in
      intact mice, and contractile performance in isolated muscle preparations were
      examined. RESULTS: Ant1-/- EOMs had the typical appearance of mitochondrial
      myopathy, including increase in mitochondrial size, number, and oxidative
      phosphorylation (OXPHOS) staining. However, there were no measurable ocular motor
      abnormalities in intact Ant1-/- mice, and their isolated EOMs did not show
      evidence of increased fatigability. EOMs of wild-type mice exhibited higher
      levels of Ant2 mRNA compared with hindlimb muscle, which may compensate for the
      Ant1 loss in mutant mouse EOMs and account for the normal EOM function.
      CONCLUSIONS: The Ant1-/- mice provide a model in which to study CPEO pathology
      and compensatory mechanisms.

PMID- 16303950
TI  - Effect of bimatoprost on intraocular pressure in prostaglandin FP receptor
      knockout mice.
AB  - PURPOSE: To determine the effect of bimatoprost on intraocular pressure in the
      prostaglandin FP receptor knockout mouse. METHODS: The IOP response to a single
      1.2-microg (4 microL) dose of bimatoprost was measured in the treated and
      untreated fellow eyes of homozygote (FP+/+, n = 9) and heterozygote (FP+/-, n =
      10) FP-knockout mice, as well as in wild-type C57BL/6 mice (FP+/+, n = 20).
      Serial IOP measurements were also performed after topical bimatoprost in a
      separate generation of homozygous FP-knockout mice and wild-type littermate
      control animals (n = 4 per group). Aqueous humor protein concentrations were
      measured to establish the state of the blood-aqueous barrier. Tissue, aqueous
      humor and vitreous concentrations of bimatoprost, latanoprost, and their C-1 free
      acids were determined by liquid chromatography and tandem mass spectrometry.
      RESULTS: A significant reduction in IOP was observed in the bimatoprost-treated
      eye of wild-type mice at 2 hours, with a mean difference and 95% confidence
      interval (CI) of the difference in means of -1.33 mm Hg (-0.81 to -1.84).
      Bimatoprost did not lead to a significant reduction in IOP in either the
      heterozygous knockout -0.36 mm Hg (-0.82 to +0.09) or homozygous FP-knockout mice
      0.25 mm Hg (-0.38 to +0.89). The lack of an IOP response in the FP-knockout mice
      was not a consequence of blood-aqueous barrier breakdown, as there was no
      significant difference in aqueous humor protein concentration between treated and
      fellow eyes. Tissue and aqueous humor concentrations of bimatoprost, latanoprost,
      and their C-1 free acids indicate that latanoprost, but not bimatoprost, is
      hydrolyzed in the mouse eye after topical administration. CONCLUSIONS: An intact
      FP receptor gene is critical to the IOP response to bimatoprost in the mouse eye.

PMID- 16303951
TI  - Reproducibility and clinical evaluation of rebound tonometry.
AB  - PURPOSE: To establish the reproducibility of a rebound tonometer in humans and
      the effect of corneal thickness on measurements, comparing it with Goldmann
      applanation tonometer. METHODS: In a first study designed to examine the
      reliability of the RBT, three experienced ophthalmologists undertook three
      consecutive intraocular pressure (IOP) measurements in 12 eyes of 12 normal
      subjects. A cross-sectional study was then performed to compare measurements
      obtained using the two tonometers in 147 eyes of 85 patients with ocular
      hypertension or glaucoma. RESULTS: Intraobserver coefficients of correlation
      obtained in the reproducibility study were 0.82, 0.73, and 0.87. Interobserver
      correlation was 0.82. There was a good correlation between IOP readings obtained
      by the RBT and the GAT (r = 0.865, P < 0.0001). RBT readings were consistently
      higher than GAT measurements (median difference, 1.8 +/- 2.8 mm Hg). A Bland
      Altman plot indicated the 95% limits of agreement between the two methods were 
      3.7 to 7.3 mm Hg (slope = -0.022, P = 0.618). Using RBT, the point that best
      discriminated between patients with an IOP < or = 21 mm Hg and those with >21 mm
      Hg, as determined by the GAT was >23 mm Hg (sensitivity, 70.5%; specificity,
      95.1%). In terms of pachymetry, the two tonometers behaved in a similar way, with
      correlation observed between IOP measurements and central corneal thickness.
      CONCLUSIONS: Rebound tonometry is a reproducible method of determining IOP in
      humans. In general, it tends to overestimate IOP compared with Goldmann
      applanation tonometry. The tonometers used in both methods are similarly affected
      by pachymetry.

PMID- 16303955
TI  - Visual field progression in glaucoma: total versus pattern deviation analyses.
AB  - PURPOSE: To compare visual field progression with total and pattern deviation
      analyses in a prospective longitudinal study of patients with glaucoma and
      healthy control subjects. METHODS: A group of 101 patients with glaucoma (168
      eyes) with early to moderately advanced visual field loss at baseline (average
      mean deviation [MD], -3.9 dB) and no clinical evidence of media opacity were
      selected from a prospective longitudinal study on visual field progression in
      glaucoma. Patients were examined with static automated perimetry at 6-month
      intervals for a median follow-up of 9 years. At each test location, change was
      established with event and trend analyses of total and pattern deviation. The
      event analyses compared each follow-up test to a baseline obtained from averaging
      the first two tests, and visual field progression was defined as deterioration
      beyond the 5th percentile of test-retest variability at three test locations,
      observed on three consecutive tests. The trend analyses were based on point-wise
      linear regression, and visual field progression was defined as statistically
      significant deterioration (P < 5%) worse than -1 dB/year at three locations,
      confirmed by independently omitting the last and the penultimate observation. The
      incidence and the time-to-progression were compared between total and pattern
      deviation analyses. To estimate the specificity of the progression analyses,
      identical criteria were applied to visual fields obtained in 102 healthy control
      subjects, and the rate of visual field improvement was established in the
      patients with glaucoma and the healthy control subjects. RESULTS: With both event
      and trend methods, pattern deviation analyses classified approximately 15% fewer
      eyes as having progressed than did the total deviation analyses. In eyes
      classified as progressing by both the total and pattern deviation methods, total
      deviation analyses tended to detect progression earlier than the pattern
      deviation analyses. A comparison of the changes observed in MD and the visual
      fields' general height (estimated by the 85th percentile of the total deviation
      values) confirmed that change in the glaucomatous eyes almost always comprised a
      diffuse component. Pattern deviation analyses of progression may therefore
      underestimate the true amount of glaucomatous visual field progression.
      CONCLUSIONS: Pattern deviation analyses of visual field progression may
      underestimate visual field progression in glaucoma, particularly when there is no
      clinical evidence of increasing media opacity. Clinicians should have access to
      both total and pattern deviation analyses to make informed decisions on visual
      field progression in glaucoma.

PMID- 16303952
TI  - Anterior optic nerve capillary blood flow response to diurnal variation of mean
      ocular perfusion pressure in early untreated primary open-angle glaucoma.
AB  - PURPOSE: To examine the impact of diurnal variation in intraocular pressure (IOP)
      and mean ocular perfusion pressure (MOPP) on the variation in anterior optic
      nerve capillary blood flow (BF) in patients with untreated early primary open
      angle glaucoma (uPOAG) and healthy volunteers. METHODS: Fourteen patients with
      uPOAG (age, 56.3 +/- 12 years [SD]; seven men) and 14 normal subjects (age, 57.6
      +/- 9.9 years; five men) were examined. Diurnal IOP, systolic (SBP) and diastolic
      (DBP) blood pressures, and optic nerve head (ONH) topography were measured every
      hour; and diurnal BF was measured by flowmeter every 2 hours between 0700 and
      2200 hours. A perfusion image analyzer was used to calculate the mean BF within
      the rim (mean rim flow, MRF). The local flow (LF) was calculated using the median
      and mean flow rates within a 10 x 10-pixel window placed on the rim in the area
      of maximum topography fluctuation (MTF). The MOPP was then calculated. Mixed
      effect linear models were used to analyze the repeated measures data in which
      both fixed and random effects were included. RESULTS: IOP, BP, and MOPP had
      significant diurnal variation (P < 0.040). LF measured at the sector of MTF
      significantly changed in patients with uPOAG (P = 0.006) but not in normal
      subjects (P = 0.660). MRF did not show significant diurnal change in either group
      (P = 0.130, P = 0.770). LF increased significantly after lunch in the uPOAG group
      (P = 0.001). SBP had a significant effect on LF over the course of the day in the
      uPOAG group (P = 0.043). The diurnal change in IOP, BP, and MOPP did not have a
      significant effect on MTF in either group. In uPOAG, the local flow, in areas of
      greatest topographical change, correlated inversely with IOP at 0700 hours (P <
      or = 0.002). CONCLUSIONS: The mean rim flow did not change during the day,
      implying that the anterior optic nerve capillary blood flow was autoregulated in
      both normal subjects and in patients with uPOAG, despite significant changes in
      IOP and MOPP. However, the regions of greatest diurnal change in rim topography
      (MTF) had significant diurnal change in capillary blood flow in patients with
      uPOAG but not in normal subjects.

PMID- 16303956
TI  - Regulation of glucocorticoid responsiveness in glaucomatous trabecular meshwork
      cells by glucocorticoid receptor-beta.
AB  - PURPOSE: Glucocorticoid administration can lead to increased intraocular pressure
      in greater than 90% of patients with primary open-angle glaucoma (POAG), compared
      with 30% to 40% of the general population. The molecular mechanisms for increased
      steroid responsiveness among patients with glaucoma are unknown. An alternative
      splicing variant of the human glucocorticoid receptor GRbeta has dominant
      negative activity and has been implicated in a variety of steroid-resistant
      diseases. GRbeta also may play a role in glucocorticoid hyperresponsiveness in
      glaucoma. METHODS: Western blot analysis was performed to detect the expression
      of GRalpha and GRbeta in TM cells and its regulation by dexamethasone (DEX).
      Immunocytochemistry was used to compare the subcellular expression of GRbeta
      between normal and glaucomatous TM cell lines. DEX transgene induction in a
      luciferase reporter was performed to investigate the differential glucocorticoid
      responsiveness between multiple normal and glaucomatous TM cell lines.
      Overexpression of GRbeta was conducted in glaucomatous TM cell lines, and the
      regulation of GRbeta in the Dex-induced reporter gene luciferase or endogenous
      myocilin and fibronectin expression were determined. RESULTS: Trabecular meshwork
      (TM) cell lines derived from normal individuals expressed higher levels of GRbeta
      than did glaucomatous TM cells. Glaucomatous TM cells were more susceptible to
      DEX induction of a luciferase reporter gene than were TM cells derived from
      normal donors. Overexpression of GRbeta in glaucomatous TM cells inhibited DEX
      induction of a luciferase reporter gene as well as the endogenous genes MYOC and
      fibronectin. CONCLUSIONS: The decreased amount of GRbeta in glaucomatous TM cells
      could result in enhanced glucocorticoid responsiveness and ocular hypertension.

PMID- 16303953
TI  - Microtubules contribute to the birefringence of the retinal nerve fiber layer.
AB  - PURPOSE: The retinal nerve fiber layer (RNFL) exhibits birefringence that is due
      to the oriented cylindrical structure of the ganglion cell axons. Possible
      birefringent structures include axonal membranes, microtubules (MTs), and
      neurofilaments. MTs are generally assumed to be a major contributor, but this has
      not been demonstrated. In this study, the MT depolymerizing agent colchicine was
      used to evaluate the contribution of MTs to RNFL birefringence. METHODS: Retinal
      nerve fiber bundles of isolated rat retina were observed through an imaging
      polarimeter set near extinction. Images were taken over an extended period.
      During baseline, the tissue was perfused with a physiological solution. During a
      treatment period, the solution was switched either to a control solution
      identical with the baseline solution or to a similar solution containing
      colchicine. The contrast of nerve fiber bundles was used to follow change of RNFL
      birefringence over time. RESULTS: When imaged by the polarimeter, birefringent
      retinal nerve fiber bundles appeared as either bright or dark stripes. Bundles
      displayed as bright stripes were used to follow changes in retardance. The
      contrast of nerve fiber bundles was stable in control experiments. However, in
      treatment experiments, bundles were bright during the baseline period, but the
      contrast of bundles decreased rapidly when the colchicine solution was applied;
      bundles were barely visible after 30 minutes of treatment. After 70 minutes, the
      bundle contrast was close to zero at all wavelengths studied (440-780 nm).
      CONCLUSIONS: MTs make a significant contribution to RNFL birefringence. The
      decrease of RNFL birefringence in glaucoma may indicate a loss of MTs.

PMID- 16303954
TI  - In vitro comparison of cytoprotective and antioxidative effects of latanoprost,
      travoprost, and bimatoprost on conjunctiva-derived epithelial cells.
AB  - PURPOSE: In a previous study, it was demonstrated that in vitro in a human
      conjunctiva-derived cell line, latanoprost in its commercial presentation
      appeared to be less toxic than the benzalkonium chloride (BAC) it contains as a
      preservative. Through a microplate cytometry technique, the investigation was
      furthered by study of whether the three commercially available antiglaucoma
      prostaglandin analogs could protect the same cell line in vitro against BAC
      toxicity and whether an antioxidative mechanism could be involved in such
      prostaglandin effects. METHODS: Human conjunctiva-derived epithelial cells from
      the Chang cell line were exposed to three prostaglandins in their commercial
      presentation (latanoprost, travoprost, and bimatoprost) and to three
      concentrations of BAC (0.02%, 0.015%, and 0.005%), corresponding to the
      concentrations contained in the three prostaglandin eyedrops. Each solution was
      diluted to 1/10 and was applied for 30 minutes Cellular membrane integrity,
      cytosolic H2O2, cytosolic O2*- and apoptosis were evaluated using neutral red,
      H2DCF-DA, hydroethidine, and Yopro-1 probes, respectively. RESULTS: Cellular
      viability decreased as BAC concentration increased, but it was accompanied by
      concentration-dependent toxicity. Toxicity of latanoprost and travoprost
      commercial solutions was statistically significantly lower than their respective
      BAC concentrations (P < 0.01), whereas bimatoprost induced no significant
      effects. There was a statistically significant decrease in H2O2 detection with
      cells exposed to latanoprost (P < 0.01) and travoprost (P < 0.01) and a lower
      detection of O2*- with cells exposed to latanoprost (P < 0.01) compared with the
      corresponding BAC concentration alone. The Yopro-1 test showed a BAC-induced
      apoptotic effect that increased with its concentration. Latanoprost and
      travoprost produced proapoptotic effects compared with control (P < 0.01), but
      these were lower than their respective preservative concentrations (statistically
      significant difference; P < 0.01). CONCLUSIONS: Latanoprost and travoprost were
      responsible for significant protective effects against BAC toxicity on
      conjunctiva-derived epithelial cells in vitro, probably related to their
      antioxidative properties. The low toxicity of the bimatoprost solution did not
      reveal a possible antioxidative effect. Reduced reactive oxygen species
      production could be the main mechanism by which prostaglandin analogs protect
      epithelial cells from the proapoptotic effects of BAC. Further studies will be
      useful to confirm this hypothesis.

PMID- 16303957
TI  - Noninvasive measurement of rodent intraocular pressure with a rebound tonometer.
AB  - PURPOSE: The present study evaluated the applicability of a rebound tonometer in
      measuring intraocular pressure (IOP) in rats and mice. METHODS: The accuracy of
      the TonoLab rebound tonometer was determined in cannulated mouse and rat eyes.
      IOP was manipulated by changing reservoir height, and tonometer pressure readings
      were recorded by an independent observer. IOP values were recorded in conscious
      Wistar rats and in four different strains of mice. The effects of anesthesia on
      IOP were evaluated in two different strains of mice. RESULTS: The IOP readings
      generated by the rebound tonometer correlated very well with the actual pressure
      in the eye. In rats, this linear correlation had a slope of 0.96 +/- 0.05 (mean
      +/- SEM, n = 4) and a Y-intercept of -2.1 +/- 1.2. In mice, the slope was 0.99 +/
      0.05 (n = 3), and the Y-intercept was 0.8 +/- 1.4. Using this method, the
      resting IOP of conscious male Wistar rats was observed to be 18.4 +/- 0.1 mm Hg
      (n = 132). In mice, strain differences in IOP were detected. Baseline IOP values
      in Balb/c, C57-BL/6, CBA, and 11- to 12-month-old DBA/2J mice were 10.6 +/- 0.6,
      13.3 +/- 0.3, 16.4 +/- 0.3, and 19.3 +/- 0.4 mm Hg (n = 12), respectively. In
      separated studies, anesthesia lowered IOP from 14.3 +/- 0.9 to 9.2 +/- 0.5 mm Hg
      (n = 8) in C57-BL/6 mice, and from 16.6 +/- 0.4 to 9.4 +/- 0.6 mm Hg (n = 10) in
      CBA mice. CONCLUSIONS: The rebound tonometer was easy to use and accurately
      measured IOP in rats and mice. This technique, together with advances in genetic
      and other biological studies in rodents, will be valuable in the further
      understanding of the etiology and pathology of glaucoma.

PMID- 16303960
TI  - Calpain may contribute to hereditary cataract formation in sheep.
AB  - PURPOSE: To determine the involvement of calpain in ovine cataractogenesis by
      measuring calcium, calpain activity, proteolysis, and the effect of calpain
      inhibition. METHODS: Sheep with genetic cataracts were examined for cataract
      severity. Calcium in normal and cataract lenses was measured. The presence of
      calpain was detected by casein zymography and immunoblotting. Calpain activity
      was assayed using BODIPY-casein as a substrate. Degradation of calpain substrates
      spectrin and vimentin was assessed by immunoblotting. The calpain inhibitor
      SJA6017 was applied to the left eye of cataract lambs, leaving the right eye as
      an untreated control. Both eyes were monitored by slit-lamp microscopy for
      cataract progression. RESULTS: Cortical cataracts were first observed in lambs at
      1 to 2 months of age. Lens calcium concentration increased in the early stages of
      cataract formation and was >10-fold higher in mature cataract than normal lenses.
      Three calpain isoforms were detected in young lamb lenses. Calpain activity
      decreased as cataracts progressed. Both spectrin and vimentin were degraded with
      cataract maturity, which could indicate calpain proteolysis. Cataract lambs
      treated with SJA6017 eyedrops over a period of 4 months showed significantly
      smaller cataracts in the left treated eye over the right untreated eye.
      CONCLUSIONS: The presence of calpains and calcium elevation during cataract
      formation suggests that proteolysis may play a role in opacification in ovine
      lens. This hypothesis is supported by the delay in opacification with SJA6017
      treatment. The results also suggested that the ovine hereditary cataract is a
      useful nonrodent model to test the role of calpains in cataractogenesis.

PMID- 16303959
TI  - TLR4 mediates human retinal pigment epithelial endotoxin binding and cytokine
      expression.
AB  - PURPOSE: It was previously demonstrated that toll-like receptor 4 (TLR4) is
      involved in species-specific human retinal pigment epithelial (HRPE)
      photoreceptor outer segment recognition and oxidant production. This study was
      performed to demonstrate the classical role of TLR4 in HRPE endotoxin
      (lipopolysaccharide; LPS) binding leading to HRPE proinflammatory cytokine
      secretion. METHODS: Cultured HRPE cells were examined for TLR4 expression by
      immunofluorescence, Western blot analysis, and RT-PCR. HRPE cells labeled with
      fluorescent monoclonal antibodies (mAbs) to TLR4 and its associated adhesion
      molecule, CD14, were analyzed by real-time microscopy and resonance energy
      transfer (RET), determining associations of fluorescent LPS, TLR4, and CD14. LPS
      induced HRPE secretion of interleukin (IL)-8 was measured with and without
      specific blocking mAb to TLR4 and CD14. HRPE TLR4 expression was measured after
      LPS exposure in the presence and absence of blocking antibodies to TLR4 and CD14.
      RESULTS: All three HRPE cell lines demonstrated constitutive TLR4 expression by
      immunofluorescence, Western blot analysis, and RT-PCR. Examination of HRPE cells
      labeled with fluorescent mAb to TLR4, CD14, and LPS demonstrated RET among the
      three molecules, indicating that LPS-CD14 binding preceded LPS-TLR4 binding and
      the close association of CD14 and TLR4. LPS-induced IL-8 was significantly
      reduced (P < 0.05) in the presence of blocking mAb to TLR4 or CD14. Upregulation
      of HRPE TLR4 gene and protein expression occurred in response to LPS exposure and
      was inhibited by mAb to TLR4 or CD14. CONCLUSIONS: HRPE TLR4 is a multifunctional
      molecule that participates in photoreceptor outer segment membrane recognition,
      oxidant production, LPS recognition, and cytokine production. These roles
      indicate potential involvement in retinal degenerative and inflammatory
      processes.

PMID- 16303958
TI  - Tryptase increases proliferative activity of human conjunctival fibroblasts
      through protease-activated receptor-2.
AB  - PURPOSE: Tryptase that is released by mast cell degranulation has recently been
      thought to play a key role in wound healing in allergic bronchitis. Conjunctival
      fibroblasts secrete mediators and extracellular matrices that could exacerbate
      inflammation and papillary formation in allergic conjunctivitis. This study was
      conducted to investigate the effect of tryptase on the proliferation of
      conjunctival fibroblasts and studied whether this effect was mediated by protease
      activated receptor (PAR)-2. METHODS: Conjunctival fibroblasts were cultured with
      or without tryptase (0.1 ng/mL to 1.0 microg/mL), and the proliferation rate was
      assessed after 48 hours. The effects of tryptase inhibitors (leupeptin,
      benzamidine) and a PAR-2 agonist (SLIGKV) were examined. The existence of PAR-2
      mRNA and protein in conjunctival fibroblasts was examined by RT-PCR and Western
      blot analysis, respectively. The existence of PAR-2 in cultured conjunctival
      fibroblasts and conjunctival papillae from patients with vernal
      keratoconjunctivitis, as well as conjunctival tissue from normal subjects was
      examined by immunohistochemistry. RESULTS: Conjunctival fibroblast proliferation
      was upregulated by tryptase in a dose-dependent manner (P < 0.001). Leupeptin and
      benzamidine inhibited tryptase-induced fibroblast proliferation (P < 0.05), and
      SLIGKV mimicked tryptase's effect. PAR-2 mRNA and protein were detected in
      cultured conjunctival fibroblasts using RT-PCR and Western blot analysis. PAR-2
      immunoreactivity in both the cultured conjunctival fibroblasts and in stromal
      cells in excised conjunctival tissues was observed. CONCLUSIONS: Tryptase
      increased conjunctival fibroblast proliferation and this response appeared to be
      mediated by PAR-2. Mast cells are the most likely source of tryptase in the
      conjunctiva and may play an important role in chronic exacerbations with
      conjunctival papillary formation in allergic conjunctivitis.

PMID- 16303961
TI  - Aggregation of lens crystallins in an in vivo hyperbaric oxygen guinea pig model
      of nuclear cataract: dynamic light-scattering and HPLC analysis.
AB  - PURPOSE: The role of oxygen in the formation of lens high-molecular-weight (HMW)
      protein aggregates during the development of human nuclear cataract is not well
      understood. The purpose of this study was to investigate lens crystallin
      aggregate formation in hyperbaric oxygen (HBO)-treated guinea pigs by using in
      vivo and in vitro METHODS: methods. Guinea pigs were treated three times weekly
      for 7 months with HBO, and lens crystallin aggregation was investigated in vivo
      with the use of dynamic light-scattering (DLS) and in vitro by HPLC analysis of
      water-insoluble (WI) proteins. DLS measurements were made every 0.1 mm across the
      4.5- to 5.0-mm optical axis of the guinea pig lens. RESULTS: The average apparent
      diameter of proteins in the nucleus (the central region) of lenses of HBO-treated
      animals was nearly twice that of the control animals (P < 0.001). Size
      distribution analysis conducted at one selected point in the nucleus and cortex
      (the outer periphery of the lens) after dividing the proteins into small-diameter
      and large-diameter groups, showed in the O2-treated nucleus a threefold increase
      in intensity (P < 0.001) and a doubling in apparent size (P = 0.03) of large
      diameter aggregate proteins, compared with the same control group. No significant
      changes in apparent protein diameter were detected in the O2-treated cortex,
      compared with the control. The average diameter of protein aggregates at the
      single selected location in the O2-treated nucleus was estimated to be 150 nm, a
      size capable of scattering light and similar to the size of aggregates found in
      human nuclear cataracts. HPLC analysis indicated that one half of the
      experimental nuclear WI protein fraction (that had been dissolved in guanidine)
      consisted of disulfide cross-linked 150- to 1000-kDa aggregates, not present in
      the control. HPLC-isolated aggregates contained alphaA-, beta-, gamma-, and zeta
      crystallins, but not alphaB-crystallin, which is devoid of -SH groups and thus
      does not participate in disulfide cross-linking. All zeta-crystallin present in
      the nuclear WI fraction appeared to be there as a result of disulfide cross
      linking. CONCLUSIONS: The results indicate that molecular oxygen in vivo can
      induce the cross-linking of guinea pig lens nuclear crystallins into large
      disulfide-bonded aggregates capable of scattering light. A similar process may be
      involved in the formation of human nuclear cataract.

PMID- 16303963
TI  - Accumulation of DNA, nuclear and mitochondrial debris, and ROS at sites of age
      related cortical cataract in mice.
AB  - PURPOSE: Lenses from young and old mice were analyzed by laser scanning confocal
      microscopy (LSCM) with vital dyes, to determine whether age-related subcapsular
      and cortical cataracts were linked to the failure of lens fiber cells to degrade
      nuclei, DNA, and mitochondria properly and whether they result in the
      overproduction of reactive oxygen species (ROS) at the same sites. RESULTS: As
      opposed to the clear DNA-free subcapsular and cortical areas of young adult mouse
      lenses, these areas in cataractous old mouse lenses were found to contain
      accumulations of nuclei, nuclear fragments, aggregated mitochondria, and
      amorphous DNA as cortical inclusions (P < 0.001 between young and old lenses).
      These inclusions correlated spatially with age-related cataracts and with the
      presence of ROS. The source of such undegraded material was a large expansion of
      transition nuclei in the bow region and also direct involution of surface lens
      epithelial cells (LECs) into the underlying cortex, frequently leaving bare
      patches devoid of nuclei on the surface of the anterior epithelium. METHODS: Live
      lenses were stained vitally for DNA with Hoechst 33342. ROS and mitochondria were
      stained and quantified with dihydrorhodamine 123 (DHR). In fixed lenses, DNA was
      stained with propidium iodide (PI) or 4',6-diamidino-2-phenylindole,
      dihydrochloride (DAPI). The intensity and position of each probe's fluorescence
      was determined by LSCM. Cataract localization was ascertained by digitalized
      microscopy of reflected light. CONCLUSIONS: In aged mice, most subcapsular and
      cortical cataracts colocalize with accumulations of nuclei, mitochondria, and
      DNA, These effects are accompanied at the same sites by the production of ROS.
      The condition is due to the failure of lens fiber cells in the bow region to
      differentiate properly into the clear fiber state and to the improper involution
      of cells from the anterior epithelium directly into the underlying cortex,
      resulting in cataractous opacities.

PMID- 16303962
TI  - Absence of SPARC in murine lens epithelium leads to increased deposition of
      laminin-1 in lens capsule.
AB  - PURPOSE: To investigate the role of SPARC in the regulation of the expression and
      deposition of extracellular matrix (ECM) proteins in the lens capsule. METHODS:
      Wild-type (SP+/+) and SPARC-null (SP-/-) mice of embryonic day (E)14 to 3 months
      of age were examined. Transcript levels of lens basement membrane (BM) components
      were analyzed by semiquantitative RT-PCR with mRNA from lens epithelia.
      Expression of ECM proteins in lens capsule and lens epithelium was analyzed by
      immunohistochemistry and Western blot analysis. Cell attachment was assessed by
      lens epithelial explant culture. Coimmunoprecipitation was performed to identify
      intracellular protein interactions. RESULTS: From postnatal day 5 to 3 months of
      age, SPARC-null lens capsules exhibited higher levels of laminin-1 deposition
      relative to their wild-type counterparts, as revealed by immunohistochemistry and
      immunoblot analysis. An uneven and aggregated distribution of laminin-1 protein
      was apparent in the anterior region of SPARC-null lens capsules. SPARC and
      laminin-1 were expressed abundantly in the endoplasmic reticulum (ER) of lens
      epithelial cells. Coimmunoprecipitation identified that SPARC associates with
      laminin-1 before laminin secretion. Furthermore, increased laminin-1 in lens
      capsule promoted the attachment of lens epithelial explants in culture.
      CONCLUSIONS: SPARC affects the secretion and deposition of laminin-1 protein in
      lens epithelial cells. Because abnormal deposition of laminin-1 in the lens BM
      could influence lens epithelial cell adhesion and fiber cell differentiation, the
      authors propose that SPARC is important to lens homeostasis through its
      regulation of lens BM matrix organization.

PMID- 16303964
TI  - Three novel Pax6 alleles in the mouse leading to the same small-eye phenotype
      caused by different consequences at target promoters.
AB  - PURPOSE: To characterize three new mouse small-eye mutants detected during
      ethylnitrosourea mutagenesis programs. METHODS: Three new mouse small-eye mutants
      were morphologically characterized, particularly by in situ hybridization. The
      mutations were mapped, and the candidate gene was sequenced. The relative amount
      of Pax6-specific mRNA was determined by real-time PCR. Reporter gene analysis
      used Crygf and Six3 promoter fragments in front of a luciferase gene and HEK293
      cells as recipients. RESULTS: The new mutations--ADD4802, Aey11, and Aey18--were
      mapped to chromosome 2; causative mutations have been characterized in Pax6
      (Aey11: C-->T substitution in exon 8, creating a stop codon just in front of the
      homeobox; ADD4802: G-->A substitution at the beginning of intron 8 changes
      splicing and leads to an altered open reading frame and then to a premature stop
      codon; Aey18: G-->A exchange in the last base of intron 5a leads also to a splice
      defect, skipping exons 5a and 6). Real-time PCR indicated nonsense-mediated decay
      in Pax6Aey11 and Pax6Aey18 mutants but not in Pax6ADD4802. This result is
      supported by the functional analysis of corresponding expression constructs in
      cell culture, where the Aey11 and Aey18 alleles did not show a stimulation of the
      Six3 promotor or an inhibition of the Crygf promoter (as wild-type constructs
      do). However, the Pax6ADD4802 allele stimulated both promoters. CONCLUSIONS:
      Together with functional analysis in a reporter gene assay and
      immunohistochemistry using Pax6 antibodies, it is suggested that the Pax6Aey11
      and Pax6Aey18 alleles act through a loss of function, whereas ADD4802 represents
      a gain-of-function allele.

PMID- 16303965
TI  - Endothelin-1 enhances glutamate-induced retinal cell death, possibly through ETA
      receptors.
AB  - PURPOSE: To determine the modification of the glutamate-induced death of retinal
      neurons by endothelin (ET)-1. METHODS: Cultured retinal neurons from fetal rats
      were exposed to glutamate (1.0 mM) alone or glutamate with ET-1 (10(-10)-10(-7)M)
      for 10 minutes. Neuronal death was assessed by the trypan blue exclusion or TUNEL
      assays at 2, 6, and 24 hours after the exposure. The effects of adding BQ-123 or
      BQ-788, ET(A), and ET(B) receptor antagonists, respectively, in combination with
      ET-1 was also assessed. RESULTS: Immunohistochemical analyses showed that the ETs
      as well as ET(A) and ET(B) receptors were expressed on cultured retinal neurons
      consisting mainly of amacrine cells. A brief exposure of the cultured retinal
      neurons to glutamate alone significantly increased the number of dead cells, and
      the addition of ET-1 with glutamate caused a further significant increase in
      retinal neuronal death compared with the cells exposed to glutamate alone. A
      significant increase in neuronal death was detected at doses of 10 nM of ET-1 and
      higher after a 24-hour exposure (P < 0.05, Dunnett), whereas brief exposure of
      neurons to up to 1 microM ET-1 alone did not cause delayed cell death of neurons.
      BQ-123 (10 nM) suppressed the enhancement of retinal toxicity caused by ET-1 (10
      nM), whereas BQ-788 had no significant effect. CONCLUSIONS: These results
      indicate that ET-1 enhances glutamate-induced retinal cell death, possibly
      through ET(A) receptors. ET-1 may act synergistically with glutamate to damage
      retinal neurons under hypoxic conditions.

PMID- 16303966
TI  - Aqueous humor dynamics in monkeys after topical R-DOI.
AB  - PURPOSE: To determine the effects of R-DOI, a selective 5-HT2 agonist, on
      intraocular pressure (IOP) and aqueous humor dynamics in monkeys. METHODS:
      Normotensive cynomolgus monkeys (n = 8) were treated topically once daily with
      four 5-muL drops of 0.5% R-DOI in one eye, vehicle in the opposite eye. The 6
      hour IOP response (Goldmann applanation tonometry) was determined before the drug
      application and on the third day of treatment. Aqueous humor formation, or flow
      (AHF, measured by fluorophotometry), was measured from hours 3 to 8 after the
      third dose. Beginning 3.5 hours after the fourth or fifth dose, AHF was measured
      by dilution of radio-iodinated monkey albumin perfused through the anterior
      chamber and flow to blood by accumulation of albumin in the general circulation.
      Uveoscleral outflow (Fu) was calculated. Flow to blood was determined at
      spontaneous and elevated pressures, allowing calculation of trabecular outflow
      facility. Total outflow facility was determined by two-level constant pressure
      perfusion from 3.5 to 5 hours and from 5.5 to 6.25 hours after R-DOI treatment.
      RESULTS: Reduction of IOP in treated eyes was compared to the opposite control
      eyes corrected for the 6-hour IOP baseline before the first dose. After the third
      dose of R-DOI, IOP was significantly (P < 0.01, n = 7) decreased by 1.4 to 4.7 mm
      Hg over the 6 hours. AHF (by fluorophotometry) increased by 13% (P < 0.05, n = 8)
      in treated compared with control eyes corrected for baseline. AHF (isotope
      dilution) increased by 30% (P < 0.01, n = 8), flow to blood decreased by 28% (n =
      5), and Fu increased by 241% (P < 0.05, n = 5). Total and trabecular outflow
      facility were unchanged. CONCLUSIONS: R-DOI caused a small but significant
      increase in AHF and lowered IOP in normotensive monkeys primarily by increasing
      Fu.

PMID- 16303967
TI  - Cytochrome P450 3A expression and activity in the rabbit lacrimal gland:
      glucocorticoid modulation and the impact on androgen metabolism.
AB  - PURPOSE: Cytochrome P450 3A (CYP3A) is an enzyme of paramount importance to drug
      metabolism. The expression and activity of CYP3A, an enzyme responsible for
      active androgen clearance, was investigated in the rabbit lacrimal gland.
      METHODS: Analysis of CYP3A expression and activity was performed on lacrimal
      gland tissues obtained from naive untreated and treated New Zealand White
      rabbits. For 5 days, treated rabbits received daily administration of vehicle or
      0.1% or 1.0% dexamethasone, in the lower cul-de-sac of each eye. Changes in mRNA
      expression were monitored by real-time RT-PCR. Protein expression was confirmed
      by Western blot. Functional activity was measured by monitoring the metabolism of
      CYP3A probe substrates-namely, 7-benzyloxyquinoline (BQ) and [3H]testosterone.
      RESULTS: Cytochrome P450 heme protein was detected at a concentration of 44.6
      picomoles/mg protein, along with its redox partner NADPH reductase and
      specifically CYP3A6 in the naive rabbit lacrimal gland. Genes encoding CYP3A6, in
      addition to the pregnane-X-receptor (PXR) and P-glycoprotein (P-gp) were
      expressed in the untreated tissue. BQ dealkylation was measured in the naive
      rabbit lacrimal gland at a rate of 14 +/- 7 picomoles/mg protein per minute.
      Changes in CYP3A6, P-gp, and androgen receptor mRNA expression levels were
      detected after dexamethasone treatment. In addition, dexamethasone treatment
      resulted in significant increases in BQ dealkylation and CYP3A6-mediated
      [3H]testosterone metabolism. Concomitant increases in CYP3A6-mediated
      hydroxylated testosterone metabolites were observed in the treated rabbits.
      Furthermore, ketoconazole, all-trans retinoic acid, and cyclosporine inhibited
      CYP3A6 mediated [3H]testosterone 6beta hydroxylation in a concentration-dependent
      manner, with IC50 ranging from 3.73 to 435 microM. CONCLUSIONS: The results
      demonstrate, for the first time, the expression and activity of CYP3A6 in the
      rabbit lacrimal gland. In addition, this pathway was shown to be subject to
      modulation by a commonly prescribed glucocorticoid and can be inhibited by known
      CYP3A inhibitors.

PMID- 16303968
TI  - Circadian fluctuations of macular edema in patients with morning vision blurring:
      correlation with arterial pressure and effect of light deprivation.
AB  - PURPOSE: This study explored the causes of vision fluctuations in patients with
      chronic macular edema. METHODS: Fifteen patients (16 eyes) with vision blurring
      at awakening due to post-central retinal vein occlusion (CRVO) macular edema
      underwent three examination sessions over 24 hours (at 7 PM, immediately after
      awakening at 7 AM, and at 7 PM), which comprised assessment of Early Treatment
      Diabetic Retinopathy Study score and measurement of macular thickness (MT) by
      optical coherence tomography. Ocular perfusion pressure was calculated from
      ambulatory arterial pressure measurement. In addition, after the 7 AM
      measurements, the patients were randomly selected for monocular light deprivation
      during the day to evaluate the role of retinal illumination in these
      fluctuations. RESULTS: Circadian fluctuation of MT was documented in all
      patients. At 7 AM, mean visual acuity (VA) was worse (mean +/- SD of the
      difference: 6.5 +/- 7.2 points; P < 0.002) and mean MT was higher (57.4 +/- 34
      microm; P < 0.001) than at 7 PM. Fluctuations of MT were correlated to
      fluctuation of arterial pressure (P = 0.05), but were not influenced by monocular
      light deprivation. CONCLUSIONS: In most patients complaining of visual
      fluctuations due to macular edema secondary to CRVO, MT and VA were found to
      undergo a circadian cycle. These short-term anatomic and functional variations
      were associated with arterial pressure variations (that is, macular thickening
      was inversely correlated to the arterial pressure drop during the night), but
      were not due to light deprivation.

PMID- 16303969
TI  - Retinal vein occlusion, homocysteine, and methylene tetrahydrofolate reductase
      genotype.
AB  - PURPOSE: The aim of this case-control study was to investigate the relationship
      between homocysteine (tHcy), 5,10 methylene tetrahydrofolate reductase (MTHFR)
      C677T genotype, folate and vitamin B12 status, and retinal vein occlusion (RVO).
      METHODS: Subjects with RVO (n = 106) were recruited from outpatient and inpatient
      sources. Controls (n = 98) were selected to achieve a similar age and sex
      distribution. Full ocular examination was performed and medical history was taken
      for each study participant. Plasma and serum samples were analyzed for tHcy level
      and folate and vitamin B12 status, and extracted DNA was assessed for the MTHFR
      C677T genotype. RESULTS: There was no significant difference in plasma tHcy level
      or thermolabile MTHFR allele frequency between subjects and controls. Similarly,
      there was no significant difference in folate or vitamin B12 status between
      subjects and controls. MTHFR genotype did not affect folate or vitamin B12
      concentrations in subjects or controls. However, tHcy was significantly higher in
      thermolabile homozygotes than in nonthermolabile homozygotes (ratio of geometric
      means, 1.35; 95% confidence interval [CI], 1.04-1.74; P = 0.024). CONCLUSIONS:
      Hyperhomocysteinemia, the MTHFR C677T mutation, and folate and vitamin B12 status
      are not important risk factors for RVO in this population.

PMID- 16303970
TI  - Choroidal hemodynamic changes during isometric exercise in patients with inactive
      central serous chorioretinopathy.
AB  - PURPOSE: Imaging studies suggest that the choroidal vasculature may be altered in
      central serous chorioretinopathy. Little is known, however, about the regulation
      of ocular blood flow in patients with central serous chorioretinopathy (CSC). The
      hypothesis for the present study was that choroidal blood flow changes during an
      increase in ocular perfusion pressure induced by isometric exercise may be
      altered in CSC. METHODS: An observer-masked, two-cohort study was performed in 14
      nonsmoking patients with chronic-relapsing but inactive CSC and in 14 healthy
      nonsmoking volunteers. Both groups were matched for age and sex. Subfoveal
      choroidal blood flow (CBF) was assessed with laser Doppler flowmetry, and ocular
      perfusion pressure (OPP) was calculated from mean arterial pressure (MAP) and
      intraocular pressure (IOP). Changes of CBF during isometric exercise over a
      period of 6 minutes were measured. RESULTS: Whereas the increase of MAP, the
      pulse rate, and the OPP were comparable between the two study groups, subfoveal
      CBF increased significantly more in the group of patients with CSC (P < 0.001).
      IOP remained unchanged in both groups during isometric exercise. At an 85%
      increase in OPP, subfoveal CBF was approximately twice as high in the patients
      with CSC compared with the healthy control group. CONCLUSIONS: The data indicate
      an abnormal subfoveal CBF regulation in patients with relapsing CSC compared with
      age-matched, nonsmoking, healthy volunteers during isometric exercise.

PMID- 16303971
TI  - Adaptation responses in early age-related maculopathy.
AB  - PURPOSE: To investigate the global-flash multifocal electroretinogram (mfERG) in
      early age-related maculopathy (ARM). METHODS: Thirty-two eyes from 20 healthy
      control subjects and 12 age-matched subjects with early ARM were investigated
      with the conventional and the global-flash mfERG. Early ARM subjects were graded
      according to an international grading system. The conventional mfERG consisted of
      103 hexagons flickering according to a pseudorandom m-sequence. The global-flash
      mfERG paradigm used four frames starting with the conventional m-sequence
      stimulation, followed by a dark frame, a global flash, and another dark frame.
      The responses include a direct response (DR) and a later induced component (IC).
      The first-order kernel peak-to-trough response densities of the conventional
      mfERG (N1P1), the global-flash DR and IC, and the implicit times of the
      conventional P1, global-flash DR, and IC peak were analyzed after averaging the
      results into five groups according to five field locations: a central area and
      four quadrants. RESULTS: There was a significant reduction of the global-flash
      mfERG DR response density (P < or = 0.05) in the early ARM group compared with
      the control group. Neither the IC response density nor DR and IC implicit times
      were significantly impaired. However, the superior retina showed longer implicit
      times than did the inferior retina for the DR in the early ARM group. There was
      no significant correlation between funduscopic features and the central averaged
      responses of the global-flash mfERG (for the DR response density: r = -0.19, P =
      0.3, or for the DR implicit time: r = -0.18, P = 0.3). None of the conventional
      mfERG parameters was significantly different between the two groups. CONCLUSIONS:
      The global-flash mfERG detects deficits in early ARM before the conventional
      mfERG. Retinal ischemia may play a role in producing function impairment in ARM.

PMID- 16303972
TI  - Intraretinal oxygen distribution in the monkey retina and the response to
      systemic hyperoxia.
AB  - PURPOSE: To measure the intraretinal oxygen distribution and consumption in the
      fovea, the parafovea, and the inferior retina in the monkey eye and determine the
      influence of graded systemic hyperoxia. METHODS: Oxygen sensitive microelectrodes
      were used to measure the oxygen tension as a function of depth through the retina
      in anesthetized monkeys (n = 8) under normoxic and hyperoxic conditions. Oxygen
      consumption rates in the avascular regions of retina were determined by fitting
      the oxygen profiles to established oxygen consumption models. RESULTS: Under
      normoxic conditions, in the foveal area, the intraretinal oxygen distribution
      reflected the absence of retinal capillaries and the predominantly choroidal
      origin of retinal oxygenation. A similar shape of oxygen distribution was seen in
      the parafoveal retina with the addition of local perturbations in the inner
      retina attributed to the presence of retinal capillaries. In the inferior retina
      the same general shape was found. Oxygen consumption in the outer retina was
      higher in the parafoveal region, and the minimum oxygen tension was lower. During
      hyperoxia, choroidal oxygen levels in all areas increased dramatically, but the
      increase in oxygen tension in the inner retina was much less. The avascular
      nature of the foveal area allowed oxygen consumption analysis of both the inner
      and outer retina and showed that inner retinal oxygen consumption increased
      significantly during hyperoxic ventilation to a level equivalent to that of the
      outer retina. CONCLUSIONS: In the outer retina of the monkey the P(O2) minimum is
      lower, and the oxygen consumption rate is higher in the parafoveal region. During
      systemic hyperoxia, outer retinal oxygen consumption is unaffected, but in the
      foveal area, total oxygen consumption increases. This regulation of oxygen
      consumption in the monkey retina is comparable to that reported in lower mammals
      and may represent an important mechanism in retinal homeostasis.

PMID- 16303973
TI  - Diagnosis of plus disease in retinopathy of prematurity using Retinal Image
      multiScale Analysis.
AB  - PURPOSE: To evaluate a semiautomated image analysis software package, Retinal
      Image multiScale Analysis (RISA), for the diagnosis of plus disease in preterm
      infants with retinopathy of prematurity (ROP). METHODS: Digital images of the
      posterior pole showing both disc and macula in preterm infants with ROP were
      analyzed with an enhanced version of RISA. Venules (N = 106) and arterioles (N =
      44) were identified, and integrated curvature, diameter, and tortuosity of the
      vessels were calculated. After the RISA calculations were completed, the origins
      of the vessels were determined to be 32 eyes in 16 infants (12 eyes with plus
      disease, 20 with no plus disease, as diagnosed by ophthalmic examination).
      Vessels were sorted into two groups-plus disease and no plus disease-and each
      RISA parameter was compared using the Mann-Whitney test. For each parameter,
      sensitivity and specificity were plotted as a function of cutoff criterion,
      receiver operating characteristic (ROC) curves were constructed, and the areas
      under the curve (AUC) were calculated. RESULTS: For both arterioles and venules,
      each of the three parameters was significantly larger for the plus disease group.
      For instance, the median estimated arteriolar and venular diameters were
      approximately 12 mum greater in plus disease. Sensitivity and specificity plots
      indicated good accuracy of each parameter for the diagnosis of plus disease. The
      AUC showed that curvature had the highest diagnostic accuracy (0.911 for
      arterioles, 0.824 for venules). CONCLUSIONS: The strong performance of RISA
      parameters in this sample suggests that RISA may be useful for diagnosing plus
      disease in preterm infants with ROP.

PMID- 16303974
TI  - ABCA4-associated retinal degenerations spare structure and function of the human
      parapapillary retina.
AB  - PURPOSE: To study the parapapillary retinal region in patients with ABCA4
      associated retinal degenerations. METHODS: Patients with Stargardt disease or
      cone-rod dystrophy and disease-causing variants in the ABCA4 gene were included.
      Fixation location was determined under fundus visualization, and central cone
      mediated vision was measured. Intensity and texture abnormalities of
      autofluorescence (AF) images were quantified. Parapapillary retina of an eye
      donor with ungenotyped Stargardt disease was examined microscopically. RESULTS:
      AF images ranged from normal, to spatially homogenous abnormal increase of
      intensity, to a spatially heterogenous speckled pattern, to variably sized
      patches of low intensity. A parapapillary ring of normal-appearing AF was visible
      at all disease stages. Quantitative analysis of the intensity and texture
      properties of AF images showed the preserved region to be an annulus, at least
      0.6 mm wide, surrounding the optic nerve head. A similar region of relatively
      preserved photoreceptor nuclei was apparent in the donor retina. In patients with
      foveal fixation, there was better cone sensitivity at a parapapillary locus in
      the nasal retina than at the same eccentricity in the temporal retina. In
      patients with eccentric fixation, approximately 30% had a preferred retinal locus
      in the parapapillary retina. CONCLUSIONS: Human retinal degenerations caused by
      ABCA4 mutations spare the structure of retina and RPE in a circular parapapillary
      region that commonly serves as the preferred fixation locus when central vision
      is lost. The retina between fovea and optic nerve head could serve as a
      convenient, accessible, and informative region for structural and functional
      studies to determine natural history or outcome of therapy in ABCA4-associated
      disease.

PMID- 16303975
TI  - Activation of matrix metalloproteinase-9 via neuronal nitric oxide synthase
      contributes to NMDA-induced retinal ganglion cell death.
AB  - PURPOSE: Understanding the mechanism of neuronal cell death in retinal diseases
      like glaucoma is important for devising new treatments. One factor involves
      excitatory amino acid stimulation of N-methyl-D-aspartate (NMDA)-type glutamate
      receptors, excessive Ca2+ influx, and formation of nitric oxide (NO) via neuronal
      NO synthase (nNOS). Another factor is the abnormal activation of matrix
      metalloproteinases (MMPs), in particular MMP-9, which triggers an extracellular
      signaling cascade leading to apoptosis. This study was designed to investigate
      the mechanism of excitotoxic retinal ganglion cell (RGC) death in vivo and its
      relationship to MMP activation. METHODS: NMDA and glycine were injected into the
      vitreous of the eye in rats and in nNOS-deficient mice (nNOS-/-) versus control.
      Gelatinolytic activity of MMP-9 and MMP-2 by zymography and cellular localization
      by immunohistochemistry were examined, and the effect of MMP inhibition on NMDA
      induced RGC death was tested. RESULTS: NMDA was found to upregulate the proform
      of MMP-9 in the retina and to increase MMP-9 gelatinolytic activity. Retrograde
      labeling with aminostilbamidine to identify RGCs confirmed that MMP activity
      occurred only in these retinal neurons and not in glial or other retinal cell
      types after excitotoxic insult. Deconvolution fluorescence microscopy revealed
      that MMP activity colocalized with immunoreactive S-nitrosylated protein. NMDA
      induced MMP activation was diminished in the retina of nNOS-/- mice, implying
      that S-nitrosylation of MMP had indeed occurred. In addition, the broad-spectrum
      MMP inhibitor GM6001 protected RGCs after intravitreal NMDA injection.
      CONCLUSIONS: These findings suggest that an extracellular proteolytic pathway in
      the retina contributes to RGC death via NO-activated MMP-9.

PMID- 16303976
TI  - Tubby-like protein 1 (TULP1) interacts with F-actin in photoreceptor cells.
AB  - PURPOSE: TULP1 is a photoreceptor-specific protein of unknown function that, when
      mutated, can cause retinitis pigmentosa in humans and photoreceptor degeneration
      in mice. Toward a better understanding of the role of TULP1 in retinal disease,
      its subcellular localization was sought and the TULP1 protein binding partners
      identified. METHODS: Immunocytochemistry and subcellular fractionation were used
      to determine the localization of TULP1 and actin in COS7 cells and photoreceptor
      cells. Immunoprecipitation from retinal lysates followed by liquid chromatography
      tandem mass spectrometry and in vitro binding assays was used to identify TULP1
      binding partners. Phospholipid binding assays were performed with a commercially
      available kit. RESULTS: TULP1 localizes at or near the plasma membrane and
      associates with the membranous fraction of COS7 cells, probably through binding
      phosphorylated phospholipids. In addition, TULP1 partitions to the aqueous phase
      during Triton X-114 extraction. Immunoprecipitation from retinal lysate
      identified F-actin as a possible TULP1-binding partner. Co-sedimentation assays
      further support an interaction between TULP1 and actin. In photoreceptor cells,
      actin and TULP1 colocalize at the inner segment, connecting cilium, and outer
      limiting membrane. CONCLUSIONS: TULP1 is a cytoplasmic protein that associates
      with cellular membranes and the cytoskeleton. TULP1 and actin appear to interact
      and colocalize in photoreceptor cells of the retina. TULP1 may be involved in
      actin cytoskeletal functions such as protein trafficking that takes place at or
      near the plasma membrane from the inner segment through the connecting cilium
      into the outer segment of photoreceptor cells.

PMID- 16303977
TI  - Cone survival despite rod degeneration in XOPS-mCFP transgenic zebrafish.
AB  - PURPOSE: In animal models of retinitis pigmentosa, rod photoreceptor degeneration
      eventually leads to loss of cone photoreceptors. The purpose of this study was to
      characterize a transgenic model of rod degeneration in zebrafish. METHODS:
      Zebrafish transgenic for XOPS-mCFP, a membrane-targeted form of cyan fluorescent
      protein driven by the Xenopus rhodopsin promoter, were generated by plasmid
      injection. Immunohistochemistry was used to detect cell type, proliferation, and
      TUNEL markers in larval and adult retinas. Rod- and cone-specific transcripts
      were detected by RT-PCR. Visual responses in transgenic adults were measured by
      electroretinogram. RESULTS: The XOPS promoter directed specific expression of
      mCFP in rods by 55 hours post fertilization (hpf). Rods in XOPS-mCFP
      heterozygotes began dying at 3.5 days post fertilization (dpf) and were almost
      completely absent by 5 dpf. A few rods were observed at the retinal margin, and
      numerous immature rods were observed in the outer nuclear layer (ONL) of
      transgenic adults. Apoptosis was increased in the ONL of larval and adult
      transgenic animals, and an elevation of rod precursor proliferation in adults was
      observed. ERG analysis confirmed that rod responses were absent in this line.
      Cone morphology and electrophysiology appeared normal in transgenic animals up to
      7 months of age. CONCLUSIONS: The XOPS-mCFP transgene causes selective
      degeneration of rods without secondary loss of cones in animals up to 7 months of
      age. This raises important questions about the significance of rod-cone
      interactions in zebrafish and their potential as a model of human inherited
      retinal degenerations.

PMID- 16303978
TI  - Soluble EphB4 regulates choroidal endothelial cell function and inhibits laser
      induced choroidal neovascularization.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of a soluble
      monomeric form of the EphB4 extracellular domain (sEphB4) on choroidal
      endothelial cell (CEC) migration and tube formation and on experimental laser
      induced choroidal neovascularization (CNV). METHODS: EphrinB2 and EphB4
      expression in CECs was investigated by Western blot analysis and
      immunohistochemistry. Effects of sEphB4 (0.5-3 microg/mL) on CEC migration were
      evaluated with a modified Boyden chamber assay. Tube formation was assayed in CEC
      cultures in collagen gel. CNV was induced in rats by laser photocoagulation. The
      effects of intravitreal injection of sEphB4 on CNV development were evaluated at
      day 14 by fluorescein angiography (FA), confocal volumetric analysis of isolectin
      B4 labeled flatmounts, and histologic examination of CNV membranes. RESULTS: CEC
      cells express both EphB4 and EphrinB2, according to Western blot analysis.
      Immunohistochemical sections of rat eye showed immunoreactivity for both EphB4
      and EphrinB2 in the choroidal endothelium. sEphB4 reduced CEC migration in
      response to vascular endothelial growth factor (P < 0.01). Similarly, sEphB4
      inhibited CEC tube formation in a dose-dependent manner. EphB4, and to a lesser
      extent EphrinB2, were detected on vascular channels within laser-induced CNV
      membranes. Intravitreal injection of sEphB4 inhibited laser-induced CNV
      formation. CNV membranes showed a reduction in leakage score (P < 0.05), and
      membrane volumes were reduced in size (P < 0.05). Histologic analysis revealed
      that vascularity was reduced in sEphB4-treated membranes. CONCLUSIONS:
      Recombinant soluble monomeric EphB4 exerts an inhibitory effect on choroidal
      angiogenesis in vitro and in vivo. It should be further evaluated for its
      potential as a novel therapy for CNV.

PMID- 16303979
TI  - Riluzole inhibits VEGF-induced endothelial cell proliferation in vitro and
      hyperoxia-induced abnormal vessel formation in vivo.
AB  - PURPOSE: The present study examined the effects of riluzole, a Food and Drug
      Administration-approved drug for amyotrophic lateral sclerosis, on VEGF
      stimulated endothelial cell proliferation in culture, and on neovascularization
      in a rat model of retinopathy of prematurity (ROP). METHODS: Human umbilical vein
      endothelial cell and bovine retinal endothelial cell cultures were treated with
      VEGF to induce endothelial cell proliferation in the presence or absence of
      riluzole. Activation of PKC betaII was examined by quantifying its phosphorylated
      form on immunoblots. ROP was induced in 5-day-old rat pups by raising them in
      hyperoxic conditions for 7 days and in normoxic conditions for the next 5 days.
      Dextran fluorescence retinal angiography was used to quantitatively assess ROP.
      RESULTS: Riluzole inhibited VEGF-stimulated PKC betaII activation and cell
      proliferation in bovine retinal endothelial cell and human umbilical vein
      endothelial cell cultures. In addition, systemic administration of riluzole
      substantially ameliorated abnormal new vessel formation in the rat ROP model.
      CONCLUSIONS: The present results suggest that riluzole is a potent inhibitor of
      VEGF-induced endothelial cell proliferation both in vivo and in vitro. Since long
      term use of riluzole has already been proven safe in humans, the present data
      indicate that clinical trials of riluzole for proliferative retinopathies should
      be implemented expeditiously.

PMID- 16303980
TI  - Synaptic pathology, altered gene expression, and degeneration in photoreceptors
      impacted by drusen.
AB  - PURPOSE: Drusen are risk factors for age-related macular degeneration and have
      been shown to negatively impact cells of the RPE and retina. In this study, the
      effects of drusen on the synaptic machinery of retinal photoreceptors are
      investigated. METHODS: Human donor eye tissue containing retina, RPE, and choroid
      was processed for confocal immunofluorescence microscopy, laser capture
      microdissection, and light and electron microscopy. Tissue sections were
      immunostained with a panel of antibodies to synapse-associated proteins.
      Populations of photoreceptors over drusen and normal populations of
      photoreceptors were microdissected from fresh frozen tissue, RNA was purified,
      and quantitative PCR was performed to compare relative levels of gene expression.
      RESULTS: The number of photoreceptor synaptic terminals is reduced in regions of
      the outer plexiform layer over drusen, synaptic proteins are mislocalized in
      photoreceptor cells, and synaptic terminals are often observed within the outer
      nuclear layer. Photoreceptors over drusen also increase expression of the stress
      response proteins apolipoprotein E and alphaB-crystallin. Abnormal immunolabeling
      patterns are not restricted to photoreceptors directly over drusen but are also
      observed in cells flanking drusen. Gene expression analysis confirms reductions
      in the expression of genes coding for synapse-associated proteins and signal
      transduction proteins and increases in the expression of apolipoprotein E and
      alphaB-crystallingene transcripts. Ultrastructural analysis of photoreceptor
      synaptic terminals over drusen reveals significant abnormalities, and cell counts
      show a reduction in photoreceptor density directly over, and lateral to, drusen
      of all sizes. CONCLUSIONS: Photoreceptors overlying and flanking drusen exhibit
      morphologic and biochemical signs of degeneration. The expression of synapse
      associated proteins decreases in photoreceptor synaptic terminals, whereas the
      expression of stress-response proteins increases. Reductions in photoreceptor
      cell densities over, and flanking, drusen suggest that these degenerative effects
      eventually result in the death of photoreceptors.

PMID- 16303981
TI  - Flavonoids protect retinal ganglion cells from oxidative stress-induced death.
AB  - PURPOSE: Mounting evidence suggests that oxidative stress contributes to the
      pathogenesis of many ocular diseases, including glaucoma and diabetic
      retinopathy. No treatments are available to prevent the neuronal degeneration
      that occurs in these disorders. The purpose of this study was to determine
      whether flavonoids, natural products that are abundant in fruits and vegetables,
      can protect retinal ganglion cells from oxidative stress-induced death. METHODS:
      The ability of flavonoids to protect an immortalized retinal ganglion cell line,
      RGC-5 cells, was tested using three model systems of oxidative stress-induced
      cell death: glutathione (GSH) depletion, t-butyl peroxide (t-BOOH) treatment, and
      hydrogen peroxide (H2O2) treatment. RESULTS: GSH depletion causes retinal
      ganglion cell death by a pathway involving the production of endogenous reactive
      oxygen species (ROS), whereas the other two treatments use exogenous sources of
      ROS. It was found that specific flavonoids could protect retinal ganglion cells
      from cell death initiated by all three of the inducers of oxidative stress with
      high levels of potency and low toxicity. In the case of GSH depletion, different
      flavonoids could be shown to act at distinct steps in the cell death pathway.
      Several of the protective flavonoids also induced the synthesis of the
      transcription factor NF-E2-related factor 2 and phase 2 antioxidant enzymes such
      as heme oxygenase 1, markers for the activation of the antioxidant response
      element. CONCLUSIONS: These results suggest that certain flavonoids can function
      as potent and effective neuroprotective agents for retinal ganglion cells.

PMID- 16303983
TI  - Chromatic and luminance contrast sensitivities in asymptomatic carriers from a
      large Brazilian pedigree of 11778 Leber hereditary optic neuropathy.
AB  - PURPOSE: To determine whether asymptomatic 11778 LHON carriers demonstrated
      impairments in (1) chromatic red/green (R/G) and blue/yellow (B/Y) contrast
      sensitivity functions (CSF) and in (2) luminance contrast sensitivity functions
      in the spatial CSF (SCSF) and temporal CSF (TCSF) domains. METHODS: Twenty-five
      carriers (8 male, 17 female; 34.1 +/- 15.1 years of age) of homoplasmic 11778
      LHON from the same well-described family and 30 age-matched controls (17 male, 13
      female; 29.2 +/- 7.1 years of age) were tested in one eye, randomly selected. Of
      the 25 eyes tested, 18 had normal fundus, 5 had swelling and microangiopathy, and
      2 had temporal pallor. The R/G and B/Y CSFs were obtained after equiluminance
      correction with bichromatic horizontal sinusoidal gratings at 0.3, 0.7, and 2
      cycles per degree (cpd); the SCSFs were obtained with achromatic gratings at 0.3,
      2, 6, and 12 cpd; and the TCSFs were obtained at 2, 10, 20, and 33 Hz with
      sinusoidal modulation of a 2.7 degrees field with a superimposed spatial Gabor
      function. RESULTS: Differences between carriers and controls were statistically
      significant for all spatial frequencies of chromatic and luminance SCSFs, but not
      for the TCSFs. R/G equiluminance settings of carriers differed from those of
      controls (P < 0.001), requiring higher luminance in the green; B/Y equiluminance
      settings were not statistically different in carriers and controls. Fundus
      findings did not correlate with CS results. CONCLUSIONS: Luminance and chromatic
      spatial CS losses that affected all tested spatial frequencies, are reported in
      LHON asymptomatic carriers with the mtDNA 11778 mutation. No losses were found in
      the temporal CSF. An intriguing finding is that the blue system is substantially
      spared in this LHON family. These represent subclinical visual impairments in
      otherwise asymptomatic LHON carriers.

PMID- 16303982
TI  - Acute aminoglycoside retinal toxicity in vivo and in vitro.
AB  - PURPOSE: Intentional and inadvertent intraocular administration of
      aminoglycosides is associated with cases of retinal toxicity. Clinical
      manifestations resemble a vaso-occlusive event and include edema, intraretinal
      hemorrhage, and nonperfusion detected by fluorescein angiogram. This study was
      conducted to measure the retinal function in avascular and isolated perfused
      retinas to separate vascular and neurologic effects of gentamicin. Enhanced
      understanding of the mechanism of gentamicin toxicity may lead to development of
      aminoglycosides that can be used to treat ophthalmic infections without retinal
      damage. METHODS: Whole animals and isolated rabbit and rat retina preparations
      were used to study the dose dependence and reversibility of toxicity on the ERG,
      with a 1- and a 10-mg/mL solution of gentamicin. The amplitude and implicit times
      of the a-, b-, and c-waves were measured before, during, and after exposure to
      the drug. RESULTS: In whole-animal ERG studies, intraocular administration of
      gentamicin eliminated the b-wave but left the a-wave intact. The c-wave was
      reduced in amplitude. Histopathologic evaluation demonstrated diffuse disruption
      of the nerve fiber layer and the inner plexiform layers. Isolated retinal studies
      showed that the b-wave was reduced in amplitude in the presence of low-dose
      gentamicin (1 mg/mL) and completely eliminated by high-dose gentamicin (10
      mg/mL). This effect was reversible for short-term exposure to gentamicin.
      CONCLUSIONS: The results indicate that the initial loss of function due to
      exposure to aminoglycoside antibiotics is independent of the vascular supply.
      Elimination of the b-wave was dose dependent and reversible, indicating that a
      component of gentamicin toxicity is mediated through pathways other than vascular
      supply. Short-term effects are reversible, suggesting a receptor-mediated
      process.

PMID- 16303985
TI  - Generic substitution of antihypertensive drugs: does it affect adherence?
AB  - BACKGROUND: Generic substitution is an important opportunity to reduce the costs
      of pharmaceutical care. However, pharmacists and physicians often find that
      patients and brand-name manufacturers have doubt about the equivalence of the
      substituted drug. This may be reflected by decreased adherence to therapy.
      OBJECTIVE: To assess the association between generic substitution and
      nonadherence to antihypertensive drugs. METHODS: We conducted a matched cohort
      study between January 1, 1999, and December 31, 2002. Data were obtained from
      PHARMO, a record linkage system containing drug-dispensing records from community
      pharmacies and linked hospital discharge records of approximately 950,000 people
      in The Netherlands. Residents of 30 medium-sized cities who initiated
      antihypertensive drug therapy were potential subjects. Refill adherence with
      antihypertensive drugs after substitution was determined; those with refill
      adherence below 80% were considered nonadherent. RESULTS: Four hundred sixty
      three patients with a substitution in therapy and 565 controls, matched on age,
      gender, therapy start date, duration of use, and generic product code, were
      identified. Of the patients who switched from brand-name to generic formulations
      ("substituted"), 13.6% were nonadherent, and of the non-substituted patients
      (those who did not switch to generic), 18.7% were nonadherent (OR 0.68; 95% CI
      0.48 to 0.96). The association was absent in males. None of the patients
      discontinued the medication. No differences in hospitalizations for
      cardiovascular disease in the 6 months after the substitution were observed.
      CONCLUSIONS: Generic substitution of antihypertensive drugs does not lead to
      lower adherence or more discontinuation and cardiovascular disease-related
      hospitalizations compared with brand-name therapy. When a less-expensive
      antihypertensive generic equivalent becomes available, generic substitution
      should be considered to achieve economic benefits.

PMID- 16303986
TI  - AGI-1067: a novel vascular protectant for prevention of restenosis.
AB  - OBJECTIVE: To review the synthesis, pharmacology, clinical trials, and adverse
      effects of AGI-1067, a novel agent for preventing restenosis. DATA SOURCES:
      Literature searches were conducted using MEDLINE (1966-July 2005) and
      International Pharmaceutical Abstracts (1970-July 2005) for English-language
      articles containing the search terms AGI-1067, AGI 1067, and probucol. In
      addition, bibliographies from relevant articles were reviewed for additional
      references. STUDY SELECTION AND DATA EXTRACTION: All articles identified from
      data sources were reviewed for relevant information. Applicable information was
      included in this review. DATA SYNTHESIS: AGI-1067, a derivative of the lipid
      lowering agent probucol, is the first of a new class of drugs termed vascular
      protectants. It has antioxidant and lipid-lowering effects. In addition, it
      inhibits inflammatory processes without resultant immunosuppression through its
      selective inhibition of vascular cell adhesion molecule-1 expression. AGI-1067
      also exhibited anti-atherosclerotic effects in preclinical studies. Relatively
      short-term treatment with AGI-1067 showed positive results compared with probucol
      in preventing restenosis in patients undergoing percutaneous coronary
      intervention. AGI-1067 appears to be well tolerated and holds important
      advantages over probucol in that it has fewer adverse effects on high-density
      lipoprotein cholesterol and the QT interval. CONCLUSIONS: The favorable safety
      profile of AGI-1067 offers potential advantages over its precursor, probucol.
      Preclinical and clinical studies indicate that it possesses antioxidant,
      antiinflammatory, and lipid-lowering properties. Ongoing Phase II and III studies
      will determine AGI-1067's place in therapy for the prevention of restenosis and
      reduction in cardiovascular events in patients undergoing percutaneous
      intervention for coronary atherosclerosis.

PMID- 16303984
TI  - Pharmacist-provided quantitative heel ultrasound screening for rural women at
      risk of osteoporosis.
AB  - BACKGROUND: Osteoporosis is underdiagnosed, and rural communities often have
      limited technical resources for the assessment of osteoporosis. OBJECTIVE: To
      evaluate the impact of a pharmacist, trained in the use of a portable heel
      ultrasound device, in screening elderly rural women for risk of osteoporosis and
      determine whether those found to be at risk seek further help and treatment from
      their general practitioner (GP) following screening. METHODS: Following promotion
      of the service, 345 women were recruited from 6 rural community pharmacies in
      Tasmania, Australia, and underwent quantitative heel ultrasound screening. Women
      were comprehensively educated on risk factors for osteoporosis and completed a
      calcium intake questionnaire. Results were forwarded to each woman's GP, and the
      participants were followed up 3 months later to assess outcomes from the
      screening procedure. RESULTS: Approximately 20% of women were shown to be at high
      risk for osteoporosis; 201 (58%) of these were referred to their GP for further
      assessment. Sixty-eight percent of women who were screened discussed their
      results with their GP, and 11% underwent further investigation. Over one-third of
      women screened began medication (30% calcium, 6% bisphosphonate, 6% vitamin D)
      for osteoporosis. CONCLUSIONS: Pharmacist-provided screening for osteoporosis in
      rural areas is a potentially useful method to identify women at risk for fracture
      and a convenient time point for discussion of preventive therapy.

PMID- 16303987
TI  - Medication utilization patterns and methods of suicidality in borderline
      personality disorder.
AB  - BACKGROUND: Borderline personality disorder (BPD) is a psychiatric disorder
      characterized by suicidal thoughts/attempts and instability of mood,
      interpersonal relationships, and self-image. Patients with BPD engage in
      manipulative acts in apparent attempts to exert control in their interpersonal
      relationships. This issue of control may also be exhibited in their manner of
      self-medication. OBJECTIVE: To examine the medication utilization patterns of
      patients with BPD versus patients without personality disorders in a control
      group and to compare methods of suicidality between the groups. METHODS: A
      randomized, retrospective, chart review study was conducted at an academic
      medical center psychiatric hospital. The study examined the medication
      utilization patterns and methods of suicidality displayed over a one-year period
      for 29 patients hospitalized with BPD versus 29 patients in a control group.
      RESULTS: The number of psychotropic, non-psychotropic, and total drugs on
      admission and discharge was significantly greater for patients with BPD compared
      with patients in the control group. There was no significant difference between
      the 2 groups with respect to overdose and cutting methods of suicidality. The
      mean number of Axis III discharge diagnoses in the control group upon discharge
      was significantly less than that in the study group. Approximately 25% of
      patients with BPD considered overdosage as a means to end their life.
      CONCLUSIONS: As patients with BPD receive more medications than patients without
      the disorder and often exhibit suicidal thoughts/attempts, clinicians should
      closely monitor the use of all medications.

PMID- 16303988
TI  - Imaging for whom: patient or physician?
AB  - OBJECTIVE: Radiologic imaging examinations are being ordered beyond the margin of
      medical necessity. Radiologists can assess the value of imaging in a variety of
      clinical situations by gathering data regarding test ordering patterns and their
      effects on patient outcomes. CONCLUSION: Emerging information technologies have
      the potential to facilitate the collection of data and permit the dissemination
      of appropriate guidelines to limit the number of unnecessary and possibly harmful
      examinations.

PMID- 16303989
TI  - Cost accounting in radiology: new directions and importance for policy.
AB  - OBJECTIVE: The purpose of this article is to promote insight into radiology costs
      through improvements in assessing patient-level cost data. Accurate patient
      costing is a prerequisite for establishing a proper payment system-one where the
      price paid for a service approximates the cost of delivering that service. In the
      absence of an accurate payment scheme, margins can vary significantly from one
      patient to the next. CONCLUSION: The resulting financial incentives skew the
      radiology marketplace away from the provision of efficient and appropriate care
      toward the selection of patients whose costs are low relative to reimbursements.

PMID- 16303990
TI  - Update on the diagnostic radiologist employment market: findings through 2004.
AB  - OBJECTIVE: The objective of this article is to summarize the latest information
      concerning the diagnostic radiologist employment market. MATERIALS AND METHODS:
      Three sources of data are presented and compared with previous data: vacancies in
      academic radiology departments as of July; the ratio of job listings to job
      seekers at a major placement service; and the number of positions advertised in
      Radiology and the American Journal of Roentgenology. RESULTS: Vacancies in
      academic radiology departments averaged 3.9 in 2004, down 29%, and decreased for
      all subspecialties as compared with 2001, but the number of vacancies remained
      very similar to that for 2003. Job listings per job seeker were 1.1 in 2004,
      stable over the past 2 years but at the lowest level since 1997. The overall
      number of positions advertised declined by 14% in 2003 compared with 2002 and by
      an additional 17% in 2004, reaching the lowest level since 1998. In 2004, 45.3%
      of positions advertised were academic. Comparing 2003-2004 with 2001-2002, all
      geographic regions exhibited absolute declines in advertisements except the
      Northeast, which showed a 1.5% increase. Absolute increases occurred for
      musculoskeletal and emergency radiology positions. Statistically significant
      proportional decreases occurred for general radiology, vascular/interventional
      radiology, and pediatric radiology. CONCLUSION: Three separate data sources
      confirm a substantial and broad-based multiyear decline in the strength of the
      demand for diagnostic radiologists, with some shifting in relative demand for
      subspecialties. It is not clear if the decrease continued in 2004 or if 2004
      demand was similar to that of 2003. Data are relative and do not indicate the
      employment market is weak in absolute terms.

PMID- 16303991
TI  - Errors of omission.

PMID- 16303992
TI  - Width of high signal and extension posterior to biceps tendon as signs of
      superior labrum anterior to posterior tears on MRI and MR arthrography.
AB  - OBJECTIVE: The purpose of our study was to determine the accuracy of two signs
      for superior labrum anterior to posterior (SLAP) tears: increased width of high
      signal between the superior labrum and glenoid, and high signal posterior to the
      biceps tendon. MATERIALS AND METHODS: Forty-one patients with SLAP tears and 40
      patients without a tear at surgery who had undergone MRI or MR arthrography were
      retrospectively evaluated. The MR studies were combined and interpreted in a
      blinded manner. The reviewers measured the width of high signal that extended to
      the articular surface on oblique coronal images and determined whether the high
      signal extended posterior to the biceps. A Student's t test was used to determine
      statistical significance between the means of the signal width. RESULTS: High
      signal width was greater in patients with a SLAP tear than in the control group
      on both MRI and MR arthrography (both p = 0.003). The sensitivity and specificity
      of at least 2.0 mm on MRI are 39% (11/28) and 89% (24/27) and at least 2.5 mm on
      MR arthrography are 46% (6/13) and 85% (11/13). The sensitivity and specificity
      of high signal posterior to the biceps are 54% (15/28) and 74% (20/27) on MRI and
      69% (9/13) and 54% (7/13) on MR arthrography. CONCLUSION: Increased width of high
      signal has a moderate specificity but a poor positive predictive value for
      distinguishing a SLAP tear from a normal recess. In addition, labral signal
      posterior to the biceps tendon is not rare in patients with no SLAP tear.

PMID- 16303993
TI  - Radial meniscal tears: significance, incidence, and MR appearance.
AB  - OBJECTIVE: The purpose of this study was to assess the prevalence of radial
      meniscal tears at arthroscopy and the ability of MRI to detect radial tears
      preoperatively. In addition, the ability of four radiologic signs to detect
      radial tears was assessed. Those signs are the truncated triangle, cleft,
      marching cleft, and ghost meniscus signs. MATERIALS AND METHODS: Arthroscopy of
      the knee was performed by a single orthopedic surgeon on 196 consecutive
      patients. The surgeon noted each radial tear he encountered. The MR images that
      were obtained at our institution were reviewed, whereas those patients who were
      imaged elsewhere were excluded. The preoperative MRI reports were reviewed to
      assess the ability to prospectively identify radial meniscal tears. In addition,
      a retrospective analysis of the MRI studies was performed by two radiologists in
      which four radiologic signs were applied to detect radial tears. RESULTS: Twenty
      nine patients (15%) had radial tears at arthroscopy. Eighteen of the 29 patients
      had their imaging performed at our institution and were selected for review.
      There were 19 radial tears found at surgery. Seven (37%) of the 19 tears were
      identified as radial prospectively. Retrospectively, using the four signs for
      radial tears, reviewers identified 17 (89%) of 19 radial tears. CONCLUSION: A
      more accurate preoperative diagnosis may be rendered using the four described
      signs to detect radial tears, thus allowing informative preoperative counseling
      and consideration of new therapies that are available for radial meniscal repair.

PMID- 16303994
TI  - Evaluation of blunt abdominal trauma using PACS-based 2D and 3D MDCT reformations
      of the lumbar spine and pelvis.
AB  - OBJECTIVE: The purpose of this study was to show the value of 2D and 3D
      reformations of CT data from abdominal and pelvic CT performed immediately at the
      workstation using a PACS-based software program to evaluate the lumbar spine and
      pelvis in patients with blunt abdominal trauma. MATERIALS AND METHODS: We
      reviewed the abdominopelvic CT scans and conventional radiographs of the lumbar
      spine or pelvis of 156 consecutive patients with blunt abdominal trauma. The CT
      data were compared with the radiographic findings and also with the findings of
      dedicated repeat CT of the spine or pelvis, when performed. RESULTS: CT depicted
      80 fractures of the lumbar spine and 178 pelvic fractures. Radiography showed 40
      fractures of the lumbar spine and 138 pelvic fractures. No additional fractures
      were identified on dedicated repeat CT. CONCLUSION: Conventional radiographs to
      clear the lumbar spine are no longer required when abdominopelvic CT data are
      available. CT and reformatted CT data show more fractures than radiography and
      miss no fractures compared with dedicated CT of the lumbar spine or pelvis.
      Having these images immediately available through the PACS workstation saves time
      for the trauma team in the management of critically ill patients.

PMID- 16303995
TI  - MRI of merkel cell carcinoma: histologic correlation and review of the
      literature.
AB  - OBJECTIVE: The objective of this study was to determine the MRI characteristics
      of Merkel cell carcinoma, with an emphasis on histologic correlation. MATERIALS
      AND METHODS: The demographic information about 15 patients from our institution
      and their MRI examinations were retrospectively reviewed by three musculoskeletal
      radiologists by consensus for lesion location and intrinsic characteristics. The
      study group was composed of three women and 12 men who ranged in age from 48 to
      87 years, with a mean age of 75 years. Histology results of resected specimens
      were reviewed in all cases and were correlated with imaging. RESULTS: MRI showed
      skin thickening, subcutaneous reticular stranding (n = 9, 60%); multiple
      anatomically aligned subcutaneous soft-tissue masses, representing lymphatic
      tumor nodules (n = 5, 33%); lymph node enlargement with fine, compressed,
      retained fatty tissue (n = 5, 33%); nodal necrosis (n = 1); and perifascial and
      intramuscular metastases (n = 2). Histology confirmed the lymphatic nature of the
      soft-tissue Merkel cell tumors. CONCLUSION: Patients with Merkel cell tumors may
      present at imaging with subcutaneous lymphatic reticular stranding, multiple
      subcutaneous masses, and lymph node metastases. Often there is massive lymph node
      enlargement with fine, compressed, retained fatty tissue.

PMID- 16303996
TI  - Prominent vascular remnants in the calcaneus simulating a lesion on MRI of the
      ankle: findings in 67 patients with cadaveric correlation.
AB  - OBJECTIVE: Our objective was to prove through cadaveric correlation that a
      frequently seen focus of MRI signal in the calcaneus is benign. CONCLUSION: A
      characteristic focus of signal (increased T2, decreased T1) in the calcaneus near
      the attachment of the cervical and interosseous ligaments is a common, benign
      finding frequently seen on MRI of the foot and ankle.

PMID- 16303997
TI  - MRI findings of osteochondritis dissecans of the capitellum with surgical
      correlation.
AB  - OBJECTIVE: Few studies have described the MRI findings of osteochondritis
      dissecans of the capitellum. Our objective was to describe the MRI findings of 10
      patients with osteochondritis dissecans of the capitellum and to correlate the
      imaging findings with surgical findings of stability and instability. CONCLUSION:
      The MRI findings of unstable and stable osteochondritis dissecans of the
      capitellum are similar to the findings described for osteochondritis dissecans of
      the femoral condyles and talar dome. Unstable osteochondritis dissecans lesions
      are surrounded by a rim of high signal intensity or a fluid-filled cyst on T2
      weighted images. Stable osteochondritis dissecans lesions show no surrounding
      signal abnormality on T2-weighted images.

PMID- 16303998
TI  - Dialysis-related amyloidosis revisited.
AB  - OBJECTIVE: Dialysis-related amyloidosis occurs secondarily to the deposition of
      beta(2)-microglobulin. Dialysis-related amyloidosis predominantly involves the
      osteoarticular system and is clinically manifested by erosive and destructive
      osteoarthropathies, destructive spondyloarthropathy, and carpal tunnel syndrome.
      This article illustrates the radiographic, sonographic, CT, and MRI findings of
      dialysis-related amyloid arthropathies. CONCLUSION: Dialysis-related amyloidosis
      is characterized by various imaging appearances. In evaluating amyloidosis, MRI
      provides considerably more information than that obtained from conventional
      radiographic, CT, and sonographic studies.

PMID- 16303999
TI  - A fast high-resolution multislice T1-weighted turbo spin-echo (TSE) sequence with
      a DRIVen equilibrium (DRIVE) pulse for native arthrographic contrast.
AB  - OBJECTIVE: This article describes a simple method to produce native arthrographic
      contrast in a fast T1-like turbo spin-echo sequence with the use of a driven
      equilibrium pulse. CONCLUSION: Our 2D multislice turbo spin-echo sequence
      combined with a driven equilibrium pulse provides a bright signal of joint fluid
      with otherwise unchanged signal intensities as compared with a normal T1-weighted
      turbo spin-echo sequence at high spatial resolution and short scan times. Thus,
      it might represent a useful adjunct for routine joint examinations.

PMID- 16304000
TI  - Differentiation between brain tumor recurrence and radiation injury using MR
      spectroscopy.
AB  - OBJECTIVE: The purpose of our study was to explore the feasibility and utility of
      2D chemical shift imaging (CSI) MR spectroscopy in the evaluation of new areas of
      contrast enhancement at the site of a previously treated brain neoplasm.
      MATERIALS AND METHODS: Two-dimensional CSI (point-resolved spectroscopy sequence
      [PRESS]; TR/TE, 1,500/144) was performed in 29 consecutive patients (4-54 years
      old; mean age, 34 years) who had a new contrast-enhancing lesion in the vicinity
      of a previously diagnosed and treated brain neoplasm. Clinical and imaging follow
      up, and histopathology in 16 patients, were used as indicators of the identity of
      a lesion. RESULTS: Diagnostic-quality spectra were obtained in 97% of the
      patients. The Cho/Cr (choline/creatine) and Cho/NAA (choline/N-acetyl aspartate)
      ratios were significantly higher, and the NAA/Cr ratios significantly lower, in
      tumor than in radiation injury (all three differences, p < 0.0001). The Cho/Cr
      and Cho/NAA ratios were significantly higher in radiation injury than in normal
      appearing white matter (p < 0.0003 and p < 0.0001, respectively), whereas NAA/Cr
      ratios were not different (p = 0.075). Mean Cho/Cr ratios were 2.52 for tumor,
      1.57 for radiation injury, and 1.14 for normal-appearing white matter. Mean
      Cho/NAA ratios were 3.48, 1.31, 0.79, and mean NAA/Cr ratios were 0.79, 1.22, and
      1.38, respectively. When values greater than 1.8 for either Cho/Cr or Cho/NAA
      ratios were considered evidence of tumor, 27 of 28 patients could be correctly
      classified. CONCLUSION: Two-dimensional CSI MR spectroscopy can differentiate
      tumor from radiation injury in patients with recurrent contrast-enhancing
      intracranial lesions. In these lesions, the Cho/NAA and Cho/Cr ratios may be the
      best numeric discriminators.

PMID- 16304001
TI  - Characteristics of ultrasmall superparamagnetic iron oxides in patients with
      brain tumors.
AB  - OBJECTIVE: The aim of this study was to evaluate the characteristics of an
      ultrasmall superparamagnetic iron oxides (USPIO) agent in patients with brain
      tumors and to correlate changes on MRI with histopathologic data collected
      systematically in all patients. SUBJECTS AND METHODS: Nine patients with brain
      tumors were imaged before and 24 hr after administration of a USPIO at a dose of
      2.6 mg Fe/kg. Analysis of MR images included qualitative and quantitative
      comparison of the USPIO and gadolinium enhancement of brain tumors. Brain surgery
      was performed 25-112 hr after administration of the USPIO. The histopathologic
      workup included iron histochemistry with diaminobenzidine (DAB)-enhanced Perls
      stain. RESULTS: In seven of nine patients, USPIO-related changes of signal
      intensity were observed in gadolinium-enhancing brain tumors on T1- and T2*
      weighted sequences. The difference in signal intensity on T1-weighted USPIO
      series was 40.1% +/- 26.7% (mean +/- SD). On T2*-weighted USPIO series, the
      difference in signal intensity was -33.1% +/- 18.4% in solid tumor parts. Areas
      of suspected radiation necrosis did not enhance in three patients with prior
      radiation therapy. Iron histochemistry revealed the presence of iron deposits in
      macrophages in two patients. CONCLUSION: USPIO agents will not replace gadolinium
      in the workup of patients with brain tumors. Our findings suggest that USPIO
      agents seem to offer complementary information and may help to differentiate
      between brain tumors and areas of radiation necrosis. Signal intensity changes on
      T2*-weighted images might be related to the blood pool properties of the agent,
      possibly reflecting steady-state susceptibility effects.

PMID- 16304002
TI  - MRI of cranial nerve enhancement.
AB  - OBJECTIVE: In this pictorial essay, we review the MR appearance of cranial nerve
      enhancement in a variety of entities including neoplastic, infectious, and
      idiopathic diseases. CONCLUSION: MRI with contrast enhancement is a valuable tool
      for detecting and characterizing disease of the cranial nerves. Abnormal cranial
      nerve enhancement on MRI may sometimes be the first or only indication of an
      underlying disease process.

PMID- 16304003
TI  - Desmoplastic fibroma with perineural extension.

PMID- 16304004
TI  - Primary interpretation of thoracic MDCT images using coronal reformations.
AB  - OBJECTIVE: The objective of this study was to evaluate the accuracy and
      efficiency of primary interpretation of thoracic MDCT using coronal reformations
      as compared with transverse images. SUBJECTS AND METHODS: Fifty patients (18
      females, 32 males; age range, 15-93 years; mean age, 63.6 years) underwent 4-MDCT
      of the chest (detector width, 1 mm; beam pitch, 1.5). Contrast material was
      administered in 20 of the 50 patients. Coronal and transverse sections were
      reformatted into 5-mm-thick sections at 3.5-mm intervals. All available image and
      clinical data consensually reviewed by two thoracic radiologists served as the
      reference standard. Subsequently, three other thoracic radiologists independently
      evaluated reformatted coronal and transverse images at two separate review
      sessions. Each image set was assessed in 58 categories for abnormalities of the
      lungs, mediastinum, pleura, chest wall, diaphragm, abdomen, and skeleton.
      Interpretation times and number of images assessed were recorded. Sensitivity,
      specificity, and interobserver concordance were calculated. Differences in mean
      sensitivities and specificities were evaluated with Wilcoxon's signed rank test.
      RESULTS: The most common findings identified were pulmonary nodules (n = 73,
      transverse images; n = 72, coronal images) and emphysema (n = 45, transverse; n =
      40, coronal). The mean detection sensitivity of all lesions was significantly (p
      = 0.001) lower on coronal (44% +/- 26% [SD]) than on transverse (51% +/- 22%)
      images, whereas the mean detection specificity was significantly (p = 0.005)
      higher (96% +/- 5% vs 95% +/- 6%, respectively). Reporting findings for
      significantly (p < 0.001) fewer coronal images (mean, 63.0 +/- 4.6 images) than
      transverse images (mean, 91.9 +/- 8.8 images) took significantly (p = 0.025)
      longer (mean, 263 +/- 56 sec vs 238 +/- 45 sec, respectively). CONCLUSION:
      Primary interpretation of thoracic MDCT is less sensitive and more time-consuming
      using 5-mm-thick coronal reformations as compared with transverse images.

PMID- 16304005
TI  - Functional impairment in emphysema: contribution of airway abnormalities and
      distribution of parenchymal disease.
AB  - OBJECTIVE: The aim of this study was to identify ancillary morphologic features
      on high-resolution CT that modify airflow obstruction and gas transfer levels in
      individuals with emphysema. MATERIALS AND METHODS: The extent of emphysema on
      high-resolution CT was quantified by density masking in 101 patients. CT scans
      were evaluated for airway abnormalities (bronchial wall thickness, extent of
      bronchiectasis, bronchial dilatation, and evidence of small airways disease) and
      disease heterogeneity (uniformity, core-rind distribution, craniocaudal
      distribution, and lung texture). Stepwise regression analysis was used to
      determine CT features that influenced forced expiratory volume in 1 sec (FEV1)
      and the single-breath diffusing capacity for carbon monoxide (Dlco) for a given
      extent of emphysema. RESULTS: The extent of emphysema using automated estimation
      was 28.4% +/- 12.3% (mean +/- SD). On univariate analysis the extent of emphysema
      correlated strongly with FEV1 (R = -0.63, p < 0.0005) and Dlco (R = -0.63, p <
      0.0005) levels. Stepwise regression analysis revealed that bronchial wall
      thickness and the extent of emphysema were the strongest independent determinants
      of FEV1 (model R2 = 0.49; p = 0.002 and < 0.001, respectively); the extent of
      bronchiectasis and degree of bronchial dilation did not separately influence FEV1
      levels. The only morphologic features linked to Dlco levels on multivariate
      analysis were increasingly extensive emphysema and a higher proportion of
      emphysema in the core region (model R2 = 0.45; p < 0.001 and 0.002,
      respectively). CONCLUSION: The important additional CT abnormalities in
      individuals with emphysema that influence FEV1 and Dlco levels irrespective of
      disease extent are bronchial wall thickness and core-rind heterogeneity,
      respectively. These observations have implications for the accurate functional
      assessment of patients considered for lung volume reduction surgery.

PMID- 16304006
TI  - Evaluation of a rigid registration method of lung perfusion SPECT and thoracic
      CT.
AB  - OBJECTIVE: The objective of our study was to evaluate a rigid registration method
      in lung perfusion SPECT using thoracic CT as a standard. MATERIALS AND METHODS:
      The reproducibility of markers selection and the robustness of the method were
      assessed on a torso phantom. The accuracy of registration regarding the number
      and location of markers and the breathing state during CT was evaluated on eight
      patients using 10 external markers placed around the thorax before SPECT and CT
      acquisitions. The accuracy of registration was assessed using the mean errors
      (ME) between 10 markers after registration. RESULTS: Registration using external
      markers on a phantom was accurate (ME, < 3 mm) when rotation was less than 40
      degrees (p = 0.02). The accuracy of registration improved markedly from four to
      six markers for phantom (5.5-3.6 mm) and patients (11.2-9.5 mm) and then remained
      constant up to 10 markers. The ME was less when using markers that well
      encompassed the thorax for phantom and patients (p = 0.02 and p = 0.05,
      respectively). The use of four anatomic markers was not accurate (ME, 20 mm).
      CONCLUSION: The registration method is reproducible and accurate, and six
      external markers were required to get an ME of less than 10 mm in patients.

PMID- 16304007
TI  - Scanning beyond anatomic limits of the thorax in chest CT: findings, radiation
      dose, and automatic tube current modulation.
AB  - OBJECTIVE: Our objective was to determine additional radiation dose associated
      with scanning beyond the anatomic limits of the thorax in chest CT protocol and
      to assess the effect of z-axis modulation on the additional radiation dose
      associated with the scanning protocol. MATERIALS AND METHODS: "Extra" images for
      routine chest CT were defined as those above lung apices (supraapical) and those
      caudal to the lowermost portion of lung parenchyma (infrapulmonary), including
      images obtained beyond the adrenal glands (infraadrenal). One hundred and forty
      eight consecutive chest CT examinations (70 men, 78 women; age range, 15-90
      years) performed September 13-25, 2003, were reviewed to determine the number of
      supraapical, infrapulmonary, and infraadrenal extra images. All examinations were
      performed using z-axis modulation (n = 70) or fixed tube current (n = 78). The CT
      dose index volume and dose-length product (DLP) values for the extra images were
      calculated. Two radiologists reviewed these extra images for pathologic findings.
      Student's t test was used to perform the statistical analysis. RESULTS: One
      hundred forty-four (97%) examinations had supraapical extra images and 145 (98%)
      had infrapulmonary extra images. A total of 31 additional findings were observed
      in extra images. Most clinically important findings were identified in patients
      with a history of malignancy. With z-axis modulation, the mean DLP for
      supraapical and infrapulmonary extra images was 39.98 mGy x cm and 132.59 mGy x
      cm, respectively. With fixed tube current, the mean DLP for supraapical and
      infrapulmonary extra images was 30.31 mGy x cm and 95.91 mGy x cm, respectively.
      CONCLUSION: A substantial number of extra images are acquired during chest CT
      that do not add clinically important information in patients with nonmalignant
      indications. The use of z-axis modulation increased radiation dose for the extra
      images.

PMID- 16304008
TI  - Idiopathic pulmonary fibrosis: spectrum of high-resolution CT findings.
AB  - OBJECTIVE: Characteristic high-resolution CT (HRCT) findings of idiopathic
      pulmonary fibrosis (IPF) include reticulation, architectural distortion, and
      honeycombing involving mainly the lung periphery and the lower lobes. In 50% of
      IPF patients, HRCT is nonspecific. This article illustrates the HRCT findings of
      IPF correlating with the pathology. CONCLUSION: The spectrum of HRCT
      manifestations varies from typical findings that allow confident diagnosis to
      atypical patterns mimicking other diseases, including predominance of ground
      glass opacity, consolidation, nodules, and atypical distribution of lesions.

PMID- 16304009
TI  - Coronary artery calcification scoring.

PMID- 16304010
TI  - Concordance of coronary artery calcium estimates between MDCT and electron beam
      tomography.
AB  - OBJECTIVE: The objective of our study was to compare MDCT with electron beam
      tomography (EBT) for the quantification of coronary artery calcification (CAC).
      MATERIALS AND METHODS: Sixty-eight patients underwent both MDCT and EBT within 2
      months for the quantification of CAC. The images were scored in a blinded fashion
      and independently by two observers with a minimum of 7 days between the
      interpretations of images obtained from one scanner type to the other. RESULTS:
      Presence versus absence of CAC was discordant by EBT versus MDCT in 6% (n = 4) of
      the cases by observer 1, with one of these cases also discordant by observer 2.
      All cases except one (aortic calcium misidentified as CAC) were among those with
      a mean Agatston score of less than 5 present on EBT but absent on MDCT. EBT and
      MDCT scores correlated well (r = 0.98-0.99). The relative median variability
      between EBT and MDCT for the Agatston score was 24% for observer 1 and 27% for
      observer 2 and was 18% and 14%, respectively, for volume score (average for both
      observers: 27% for Agatston score and 16% for volume score). Scores were higher
      for EBT than MDCT in approximately half of the cases, with little systematic
      difference between the two (median EBT-MDCT difference: Agatston score, -0.55;
      volume score, 3.4 mm3). The absolute median difference averaged for the two
      observers was 28.75 for the Agatston score and 15.4 mm3 for the volume score.
      CONCLUSION: Differences in CAC measurements using EBT and MDCT are similar to
      interscan differences in CAC measurements previously reported for EBT or for
      other MDCT scanners individually.

PMID- 16304011
TI  - Serial electron beam CT measurements of coronary artery calcium: Has your
      patient's calcium score actually changed?
AB  - OBJECTIVE: The objective of our study was to develop a model for determining the
      smallest statistically significant change in the coronary artery calcium score
      (CAC) between serial measurements in a given subject. MATERIALS AND METHODS: We
      assembled a convenience sample of 2,217 pairs of repeated electron beam CT
      coronary calcium scans acquired in quick succession. Each scan consisted of forty
      100-msec, 3-mm sections obtained at 60% of the ECG R-R interval. A single
      observer quantified calcium in each scan independent of knowledge of calcium
      quantity in the repeated scan. We then modeled a relationship between the
      variation of the differences between repeated measurements of calcium and the
      magnitude of the calcium score and formulated 95% repeatability coefficient
      equations for the Agatston and volumetric CAC score. The equations allow
      determining the smallest statistically significant interval change in the calcium
      score between two serial measurements in a given subject. RESULTS: In a subject
      with measurable CAC at baseline, the smallest statistically significant interval
      change is +/- (4.930 x square root of baseline Agatston CAC score) or +/- (3.445
      x square root of baseline volumetric CAC score). In a subject with no measurable
      CAC at baseline, a follow-up CAC score exceeding 11.6 Agatston units or 9.5 mm3
      qualifies for statistically significant progression. The results were similar in
      men and women. CONCLUSION: By examining repeatability of quantitative electron
      beam CT measurements of coronary calcium as a function of the magnitude of the
      calcium score, we developed a model to determine the smallest statistically
      significant change between serial measurements in a given subject.

PMID- 16304012
TI  - Three-dimensional cardiac image fusion using new CT angiography and SPECT
      methods.
AB  - OBJECTIVE: The purpose of this study was to develop a method of fused images of
      coronary CT angiography and myocardial perfusion SPECT. CONCLUSION: Four patients
      with ischemic heart disease underwent 3D volume-rendering fused images using a
      conversion program and volume-rendering fusion function of a computer
      workstation. The fusion images clearly showed the relationship of relevant
      coronary arteries and the abnormal perfusion territory in all patients and were
      useful for the evaluation of coronary artery disease.

PMID- 16304013
TI  - Early postoperative hepatic sonography as a predictor of vascular and biliary
      complications in adult orthotopic liver transplant patients.
AB  - OBJECTIVE: Our objective was to quantitatively assess the value of early
      posttransplantation hepatic artery resistive indexes in predicting vascular and
      nonvascular complications in adult orthotopic liver transplant (OLT) patients.
      MATERIALS AND METHODS: Between 1999 and 2001, 110 consecutive adults received
      grafts. Doppler sonographic graft evaluations measured main, right, and left
      resistive indexes within 24 to 48 hr after surgery (normal resistive index
      cutoff, 0.6). Clinical, operative, procedural, and radiologic reports were
      reviewed for vascular and biliary complications. Frequency, Student's t test,
      logistic, and regression statistical analyses were performed. RESULTS: even
      patients (6.4%) had vascular complications, including two (1.8%) hepatic artery
      and two (1.8%) hepatic vein stenoses, one (0.9%) hepatic vein thrombosis, two
      (1.8%) portal vein thromboses, and one (0.9%) thrombosis and two (1.8%) stenoses
      of the inferior vena cava (IVC). In 19 patients (17.3%), biliary complications
      included anastomotic strictures and leaks 1 week to 18 months after
      transplantation. In 11 patients (10%), sonographically large hematomas required
      surgical evacuation. In grafts with vascular complications or large hematomas,
      the mean early posttransplant main, right, and left indexes were significantly
      lower (< or = 0.6) than without these complications (p < 0.01). In grafts with
      and without biliary complications, mean early posttransplant main, right, and
      left indexes did not differ significantly. CONCLUSION: In adult OLT patients, low
      early posttransplant hepatic artery resistive indexes were sensitive (100%) and
      specific (80%) predictors for vascular complications (e.g., hepatic artery,
      portal vein, hepatic vein, and IVC) but not for biliary complications. All
      patients with indexes less than 0.6 within 24-48 hr after surgery should be
      monitored closely for vascular complications.

PMID- 16304014
TI  - Biliary cystadenoma of the gallbladder.

PMID- 16304015
TI  - CT diagnosis of traumatic gallbladder injury.

PMID- 16304016
TI  - Diagnostic value of CT enteroclysis compared with conventional enteroclysis in
      patients with Crohn's disease.
AB  - OBJECTIVE: The objective of our study was to assess the diagnostic value of CT
      enteroclysis compared with conventional enteroclysis in patients with Crohn's
      disease. SUBJECTS AND METHODS: Fifty consecutive patients (26 women, 24 men; mean
      age, 36.3 years; age range, 18-52 years) with histologically proven Crohn's
      disease underwent CT enteroclysis and conventional enteroclysis (median time
      interval, 21.7 days) during a symptomatic stage of their disease. Both techniques
      were compared with regard to diagnostic yield in assessing the presence and
      extent of disease. Imaging findings were compared with surgery, follow-up
      examinations, or both. RESULTS: CT enteroclysis and conventional enteroclysis
      were successfully performed in all 50 patients. Crohn's disease-associated
      radiographic changes were found in 44 patients (88%) using CT enteroclysis and in
      42 patients (84%) using conventional enteroclysis. Significantly more Crohn's
      disease-associated abnormalities were diagnosed with CT enteroclysis than with
      enteroclysis (p < 0.01). Minimal inflammatory changes of the mucosa were
      diagnosed in 44 patients (88%) using CT enteroclysis and in 42 patients (84%)
      using enteroclysis. Both imaging methods depicted stenotic bowel segments in 34
      patients (68%), and prestenotic dilatation was diagnosed in 20 patients (40%)
      with CT enteroclysis and in 15 (30%) with enteroclysis. Fistulas were found in 18
      patients (36%) with CT enteroclysis and in eight (16%) with enteroclysis (p <
      0.01). Skip lesions could be seen in 17 (34%) and three patients (6%),
      respectively (p < 0.01). Conglomeration of bowel loops tumors was diagnosed with
      CT enteroclysis in 13 patients (26%) and in three patients (6%) using
      conventional enteroclysis (p < 0.01). Only CT enteroclysis depicted abscesses in
      eight patients (16%) (p < 0.01). CONCLUSION: CT enteroclysis proved to be
      significantly superior to conventional enteroclysis in depicting Crohn's disease
      associated intra- and extramural abnormalities. CT enteroclysis is the imaging
      method of choice and should replace enteroclysis in patients with Crohn's
      disease.

PMID- 16304017
TI  - Detectability of small and flat polyps in MDCT colonography using 2D and 3D
      imaging tools: results from a phantom study.
AB  - OBJECTIVE: The objective of this phantom study was to determine the performance
      of MDCT colonography for the detection of small polyps under ideal imaging
      conditions and to determine the added value of 3D imaging when used as an adjunct
      to 2D imaging. MATERIALS AND METHODS: Thirty-six polypoid and 39 flat polyps (44
      lesions, 2-5 mm; 31 lesions, 6-8 mm) were placed in three explanted segments of a
      thoroughly cleaned porcine colon (overall length, 4.5 m) that was distended with
      air and submerged in a water phantom. MDCT data sets with 4 x 1 mm collimation
      and 6-mm table feed were reconstructed every 0.7 mm with 1.25-mm effective slice
      width. The data were reviewed by three radiologists using 2D images in all three
      projections and with 3D volume-rendered images available as an adjunct to the 2D
      images. RESULTS: Additional 3D as a problem-solving tool significantly increased
      the overall sensitivity (96% vs 90%), decreased the total number of false
      positive calls (n = 9 vs n = 5), and increased the diagnostic confidence level (p
      < 0.03) compared with 2D images alone. Small polyps less than or equal to 5 mm
      (89% vs 95%, p = 0.004) and flat polyps (82% vs 94%, p = 0.001) especially
      benefited from 3D. Sensitivity was generally higher for polypoid than for flat
      polyps (99% vs 94%, p = 0.041). CONCLUSION: Under phantom conditions, simulating
      an ideal clinical setup, MDCT colonography is not limited by spatial resolution
      and detects polyps less than or equal to 5 mm in size with high sensitivity and
      specificity. Additional 3D image tools improve diagnostic accuracy and reviewer
      confidence, especially for the detection of flat and small polyps.

PMID- 16304018
TI  - Isolated fallopian tube torsion: a rare twist on a common theme.

PMID- 16304019
TI  - Radiologic-pathologic conference of the University of Ankara Medical School:
      metaplastic breast carcinoma with osteochondrosarcomatous differentiation.

PMID- 16304020
TI  - Leiomyoma of the breast parenchyma.

PMID- 16304021
TI  - Dynamic contrast-enhanced MR urography in the evaluation of pediatric
      hydronephrosis: Part 1, functional assessment.
AB  - OBJECTIVE: The purpose of our study was to derive time-intensity curves for the
      renal cortex and medulla from 3D dynamic MR urography and to assess whether these
      curves are predictive of obstruction. MATERIALS AND METHODS: Fifty-nine
      examinations were performed in 53 pediatric patients and the degree of
      obstruction assessed using the renal transit time. The cortex and medulla were
      segmented using a semiautomatic method, and mean time-intensity curves were
      derived for the segmented volumes. The basic parameters of the curves (amplitude,
      washout) were assessed, as was the presence of certain characteristic features of
      the curves. RESULTS: The images allowed clear visualization of three phases of
      the uptake of contrast material in the cortex, the medulla, and the collecting
      system. Both the amplitude of the curves and the washout of the contrast material
      were predictive of obstruction. The distal tubular peak was reliably detected in
      the cortex of nonobstructed kidneys. CONCLUSION: Combining signal-intensity
      versus-time-curve analysis with the other parameters that can be derived from the
      same MR urography data set provides a powerful tool for the diagnosis of
      obstruction.

PMID- 16304022
TI  - Dynamic contrast-enhanced MR urography in the evaluation of pediatric
      hydronephrosis: Part 2, anatomic and functional assessment of ureteropelvic
      junction obstruction [corrected].
AB  - OBJECTIVE: The purpose of our study was to retrospectively review our experience
      using MR urography in the diagnosis of ureteropelvic junction (UPJ) obstruction
      in children. MATERIALS AND METHODS: Sixty-one studies were performed in 50
      children with hydronephrosis but without hydroureter. Anatomic criteria assessed
      included degree of hydronephrosis, morphology of the renal pelvis, atrophy of
      medulla, swirling contrast material, fluid levels, and the presence of fetal
      folds and crossing vessels. Functional criteria included renal transit time,
      differential renal function, and time-intensity curves when available. RESULTS:
      Thirty-one kidneys were classified as obstructed, 15 as equivocal, and 15 as
      nonobstructed. Obstructed systems had more marked hydronephrosis, more extensive
      medullary atrophy, more fluid levels, and more swirling contrast material. Fetal
      folds were seen in only the equivocal and nonobstructed groups. Crossing vessels
      were seen in all groups. Obstructed systems also showed greater functional
      derangement, decreased split renal function, and abnormal time-intensity curves.
      CONCLUSION: MR urography provides both excellent anatomic and functional
      information in children with UPJ obstruction in a single test that does not use
      ionizing radiation. MR urography may lead to greater understanding of the
      pathophysiology of UPJ obstruction.

PMID- 16304023
TI  - Percutaneous declotting of virgin femoral hemodialysis grafts.
AB  - OBJECTIVE: The objective of our study was to evaluate outcomes of percutaneous
      declotting procedures in patients with prosthetic femoral dialysis grafts.
      MATERIALS AND METHODS: A retrospective review of all pharmacomechanical femoral
      dialysis graft declotting procedures performed in our hospital between May 11,
      1993, and April 30, 2003, was performed. A total of 110 procedures were performed
      on 25 patients (nine males, 16 females; age range, 17-80 years; mean age, 49
      years) with 30 grafts. RESULTS: Technical success was 97.3%. Using life table
      analysis, 30-day postinterventional primary patency was 72%, 90-day primary
      patency was 46%, 180-day primary patency was 25%, and 365-day primary patency was
      4%. The 30-day secondary postinterventional patency was 93%, 90-day secondary
      patency was 86%, 180-day secondary patency was 76%, and the 365-day secondary
      patency was 51%. An average of 1.96 declotting procedures were performed per year
      of dialysis. CONCLUSION: Percutaneous declotting of femoral hemodialysis grafts
      has technical success and patency rates similar to those for percutaneous
      declotting in the upper extremities. Results of this series exceeded criteria
      established by the National Kidney Foundation in the "Dialysis Outcome Quality
      Initiative" for immediate patency and unassisted 3-month patency.

PMID- 16304024
TI  - Safety and efficacy of preoperative portal vein embolization with polyvinyl
      alcohol in 58 patients with liver metastases.
AB  - OBJECTIVE: The objective of our study was to evaluate the safety and efficacy of
      transhepatic lobar portal vein embolization (PVE) using polyvinyl alcohol (PVA)
      particles to induce contralateral lobar hypertrophy in patients with liver-only
      metastases and normal underlying liver function. MATERIALS AND METHODS: Fifty
      eight consecutive patients with small predicted future liver remnants (FLRs)
      underwent PVE with PVA particles to induce hypertrophy of the contralateral hemi
      liver before surgical resection of liver metastases. Total liver, right hemi
      liver, and left hemi-liver volumes were calculated before and after embolization
      using a 3D workstation. RESULTS: Eight patients underwent left PVE; 47, right
      PVE; and three, right and segment IV PVE. There were no major complications of
      the procedure. The mean increases in the ratio of the FLR to the total estimated
      liver volume after right, right and segment IV, and left PVE were 9%, 10%, and
      3%, respectively; the corresponding mean hypertrophy ratios were 24.3%, 31.9%,
      and 1.5%, respectively. CONCLUSION: Right PVE using PVA particles alone as the
      embolic agent is safe and effective in achieving left hemi-liver hypertrophy. In
      contrast, left PVE did not induce significant right hemi-liver hypertrophy in
      this patient population.

PMID- 16304025
TI  - Thermal damage of the genitofemoral nerve due to radiofrequency ablation of renal
      cell carcinoma: a potentially avoidable complication.
AB  - OBJECTIVE: A technique is presented that may prevent damage to the genitofemoral
      nerve during percutaneous radiofrequency ablation of renal cell carcinomas. The
      genitofemoral nerve originates from the upper part of the lumbar plexus and
      descends laterally along the psoas major muscle, which is anatomically close to
      the kidney. During radiofrequency ablation, nearby healthy nerve tissue could be
      damaged by heat conductance. In the described technique, the radiofrequency
      applicator within the renal tumor is used as a lever to displace the kidney away
      from the psoas muscle. CONCLUSION: Three clinical cases are presented in this
      study. In one case, the technique was not applied, leading to coagulation of the
      genitofemoral nerve. In the other two cases, hazard to the genitofemoral nerve
      was averted by using the mentioned technique.

PMID- 16304026
TI  - Is true FISP imaging reliable in the evaluation of venous thrombosis?
AB  - OBJECTIVE: The objective of our study was to evaluate the accuracy of true fast
      imaging with steady-state precession (FISP) in the diagnosis of venous thrombosis
      using gadolinium-enhanced 3D T1-weighted gradient-echo images and correlative
      imaging as the gold standard. MATERIALS AND METHODS: Twenty-five MR examinations
      were retrospectively reviewed independently by two radiologists to rule out
      thrombosis in the central veins of the body. The presence of venous thrombus was
      assessed separately in 80 veins using true FISP and gadolinium-enhanced T1
      weighted images. Diagnosis was confirmed by another imaging technique
      (sonography, CT, and/or conventional venography) in all positive cases. Negative
      examinations were confirmed using imaging, clinical follow-up, or both. RESULTS:
      Venous thrombosis was present in 25 veins in 18 patients. True FISP images had a
      lower sensitivity (66%) and specificity (70.9%) for the diagnosis of venous
      thrombosis than gadolinium-enhanced MR images (p < 0.01). CONCLUSION: True FISP
      images have lower sensitivity and specificity in the diagnosis of venous
      thrombosis than gadolinium-enhanced T1-weighted gradient-echo images. True FISP
      images should not be used exclusively for the diagnosis of venous thrombosis.

PMID- 16304027
TI  - Assessment of critical limb ischemia in patients with diabetes: comparison of MR
      angiography and digital subtraction angiography.
AB  - OBJECTIVE: The purpose of our study was to evaluate the diagnostic accuracy of
      hybrid MR angiography by comparison with digital subtraction angiography (DSA) in
      diabetic patients with critical limb ischemia. SUBJECTS AND METHODS: Thirty-one
      patients prospectively underwent both hybrid MR angiography and DSA. The hybrid
      MR angiography study consisted of high-resolution MR angiography of a single calf
      and foot using a contrast-enhanced 3D gradient-echo volumetric interpolated
      breath-hold examination with surface coils, followed by three-station bolus chase
      MR angiography with a dedicated peripheral vascular coil. Two blinded reviewers
      separately analyzed maximum-intensity-projection hybrid MR angiograms and DSA
      images. The peripheral vessels were divided into 10 anatomic segments for review.
      The status of each segment was graded as normal, stenosis less than 50% in
      diameter, stenosis greater than 50%, or occluded. The sensitivity and specificity
      of hybrid MR angiography were determined using DSA as the gold standard.
      Treatment options were considered separately from the results of each
      examination. RESULTS: Among 310 analyzed segments, the sensitivities of hybrid MR
      angiography for stenosis and occlusion were, respectively, 95% and 95% for
      reviewer 1 and 96% and 90% for reviewer 2. The specificities of hybrid MR
      angiography for stenosis and occlusion were, respectively, 98% and 98% for
      reviewer 1 and 98% and 99% for reviewer 2. In 25 patients (81%), the quality of
      bolus chase MR angiography images was insufficient to assess runoff arteries. All
      treatments proposed on the basis of DSA findings were endorsed by hybrid MR
      angiography findings. Eleven more treatments were formulated on the basis of
      hybrid MR angiography findings. Of these, four were due to overestimation of
      stenosis on MR angiography and seven were due to the detection of patent
      infrageniculate arteries on hybrid MR angiography that were not detected on DSA.
      CONCLUSION: Hybrid MR angiography depicts runoff arteries not seen on DSA. Hybrid
      MR angiography may be useful for treatment planning in selected diabetic patients
      with critical limb ischemia.

PMID- 16304028
TI  - FDG PET and SPECT of bone metastases in breast cancer.

PMID- 16304029
TI  - Midbrain ataxia.

PMID- 16304030
TI  - The acronym "PCP" is Pneumocystis pneumonia, not Pneumocystis carinii pneumonia.

PMID- 16304031
TI  - Fertility enhancement by hysterosalpingography with oil-soluble contrast media:
      reality not myth.

PMID- 16304033
TI  - Age-standardized abdominal esophageal length: can body weight be a confounding
      factor?

PMID- 16304035
TI  - Reducing radiation dose to pediatric patients.

PMID- 16304036
TI  - Removing hidden patient data from digital images in PowerPoint.
AB  - OBJECTIVE: The purpose of this article is to discuss the potential issue of
      exposing patient information from digital images used in PowerPoint
      presentations. CONCLUSION: Current methods for safeguarding patient information
      in PowerPoint presentations still contain the potential for risk. In radiology,
      many digital images used in PowerPoint contain hidden patient identification
      information. Although cautious use of cropping and masking techniques has been
      adequate for presentation, the hidden information is still available as part of
      the digital image and may pose Health Insurance Portability and Account-ability
      Act (HIPAA) risks. This article will discuss the origin of this issue and
      describe simple solutions for permanently removing patient information using
      built-in PowerPoint functions.

PMID- 16304037
TI  - MDCT demonstration of intralobar pulmonary sequestration of the right upper lobe
      in an adult.

PMID- 16304038
TI  - Resolution of temporal lobe epilepsy and MRI abnormalities after coiling of a
      cerebral aneurysm.

PMID- 16304040
TI  - Imaging the anatomy of the brachial plexus: review and self-assessment module.
AB  - OBJECTIVE: The educational objectives of this continuing medical education
      activity are to describe the normal anatomy of the brachial plexus, to name the
      most common symptoms associated with a brachial plexopathy, to describe the most
      common imaging findings resulting from trauma to the brachial plexus, to describe
      the imaging manifestations of common neoplasias affecting the brachial plexus,
      and to also describe the imaging findings and symptoms related to irradiation
      induced brachial plexopathies. CONCLUSION: In this article, I have illustrated
      and described the normal anatomy of the brachial plexus; the most common symptoms
      related to brachial plexopathy; and imaging findings related to trauma, tumors,
      and irradiation affecting the brachial plexus.

PMID- 16304041
TI  - Radiological reasoning: male breast mass with calcifications.
AB  - OBJECTIVE: We encountered a mammographically calcified breast mass in a 30-year
      old man. It was initially thought to be comedo-type ductal carcinoma in situ
      because of the dense calcifications, but sonography and MRI suggested a highly
      vascular lesion. The final pathologic diagnosis was hemangioma. CONCLUSION:
      Vascular tumors of the breast occur infrequently and are even more rare in males.
      The clinical and radiologic diagnosis of breast hemangioma is often difficult,
      but different imaging techniques, when used together, can provide important
      information for differential diagnosis and management. A biopsy is required.

PMID- 16304043
TI  - B-lymphocyte stimulator (BLyS) stimulates immunoglobulin production and malignant
      B-cell growth in Waldenstrom macroglobulinemia.
AB  - Waldenstrom macroglobulinemia (WM) is a serious and frequently fatal B-cell
      malignancy associated with an elevated monoclonal IgM protein in the serum. Many
      of the mechanisms leading to this disease are not yet known. B-lymphocyte
      stimulator (BLyS) is a TNF family member that is critical for maintenance of
      normal B-cell development and homeostasis. BLyS is overexpressed in a variety of
      B-cell malignancies and has been shown to inhibit apoptosis in malignant B cells.
      It also regulates immunoglobulin secretion by normal B cells. To determine the
      relevance of BLyS in WM, we examined the role of BLyS in WM patient samples.
      Malignant B cells were found to bind soluble BLyS and variably express the
      receptors BAFF-R, TACI, and BCMA. We also found expression of BLyS in bone marrow
      specimens by immunohistochemistry and elevated serum BLyS levels in patients with
      WM. BLyS, alone or in combination with cytokines that induce immunoglobulin
      production, was found to increase IgM secretion by malignant B cells.
      Furthermore, BLyS was found to increase the viability and proliferation of
      malignant B cells from WM patients. Due to the role of BLyS in WM, strategies to
      inhibit BLyS may potentially have therapeutic efficacy in these patients.

PMID- 16304044
TI  - Hypoxic induction of an HIF-1alpha-dependent bFGF autocrine loop drives
      angiogenesis in human endothelial cells.
AB  - Hypoxia is a major pathophysiological condition for the induction of
      angiogenesis, which is a crucial aspect of growth in solid tumors. In mammalian
      cells, the transcriptional response to oxygen deprivation is largely mediated by
      hypoxia-inducible factor 1 (HIF-1), a heterodimer composed of HIF-1alpha and HIF
      1beta subunits. However, the response of endothelial cells to hypoxia and the
      specific involvement of HIF-alpha subunits in this process are still poorly
      understood. We show that human umbilical vein endothelial cells (HUVECs) cultured
      in the absence of growth factors survive and form tubelike structures when
      cultured under hypoxic, but not normoxic, conditions. HUVECs expressed both HIF
      1alpha and HIF-2alpha when cultured under hypoxic conditions. Transfection of HIF
      1alpha, but not HIF-2alpha, siRNA to HUVECs completely abrogated hypoxic
      induction of cords. Neutralizing antibodies to bFGF, but not IGF-1, VEGF, or PDGF
      BB, blocked survival and sprouting of HUVECs under hypoxic conditions, suggesting
      the existence of an autocrine loop induced by low oxygen levels. Notably, bFGF
      dependent induction of cord formation under normoxic conditions required HIF
      1alpha activity, which was also essential for hypoxic induction of bFGF mRNA and
      protein expression. These results uncover the existence of an HIF-1alpha-bFGF
      amplification pathway that mediates survival and sprouting of endothelial cells
      under hypoxic conditions.

PMID- 16304045
TI  - Chemokine and chemokine receptor expression during colony stimulating factor-1
      induced osteoclast differentiation in the toothless osteopetrotic rat: a key role
      for CCL9 (MIP-1gamma) in osteoclastogenesis in vivo and in vitro.
AB  - Osteoclasts differentiate from hematopoietic precursors under systemic and local
      controls. Chemokines and receptors direct leukocyte traffic throughout the body
      and may help regulate site-specific bone resorption. We investigated bone gene
      expression in vivo during rapid osteoclast differentiation induced by colony
      stimulating factor 1 (CSF-1) in Csf1-null toothless (tl/tl) rats. Long-bone RNA
      from CSF-1-treated tl/tl rats was analyzed by high-density microarray over a time
      course. TRAP (tartrate-resistant acid phosphatase)-positive osteoclasts appeared
      on day 2, peaked on day 4, and decreased slightly on day 6, as marrow space was
      expanding. TRAP and cathepsin K mRNA paralleled the cell counts. We examined all
      chemokine and receptor mRNAs on the arrays. CCL9 was strongly induced and peaked
      on day 2, as did its receptor, CCR1, and regulatory receptors c-Fms (CSF-1
      receptor) and RANK (receptor activator of nuclear factor kappaB). Other
      chemokines and receptors showed little or no significant changes. In situ
      hybridization and immunohistochemistry revealed CCL9 in small, immature
      osteoclasts on day 2 and in mature cells at later times. Anti-CCL9 antibody
      inhibited osteoclast differentiation in culture and significantly suppressed the
      osteoclast response in CSF-1-treated tl/tl rats. While various chemokines have
      been implicated in osteoclastogenesis in vitro, this first systematic analysis of
      chemokines and receptors during osteoclast differentiation in vivo highlights the
      key role of CCL9 in this process.

PMID- 16304046
TI  - FLT3-ITD-, but not BCR/ABL-transformed cells require concurrent Akt/mTor blockage
      to undergo apoptosis after histone deacetylase inhibitor treatment.
AB  - Leukemias are differentially sensitive to histone deacytelase inhibitor (HDI)
      induced apoptosis, but molecular reasons for this remain unclear. We here show
      that BCR/ABL-, but not FMS-like tyrosine kinase 3 (FLT3)-internal tandem
      duplication (ITD)-transformed 32D cells or primary acute myeloid leukemia (AML)
      blasts undergo apoptosis after treatment with the HDI valproic acid (VPA) plus
      all-trans retinoic acid (VPA/ATRA). A particular VPA/ATRA responsiveness of
      Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (ALL) was
      confirmed in a therapy-refractory patient in vivo. HDI-stimulated apoptosis in
      Ph+ cells was caspase dependent, but independent from Akt pathway inhibition.
      Conversely, separate blockage of the Akt/mTor-signaling pathway was a
      prerequisite for overcoming apoptosis resistance to VPA/ATRA in FLT3-ITD cells,
      and primary AML blasts (n = 9). In conclusion, constitutive Akt activation causes
      apoptosis resistance to VPA/ATRA in AML, but not in Ph+ leukemia. This warrants
      the application of HDI-based therapies in poor-risk Ph+ ALL, and the use of
      Akt/mTor inhibitors to overcome HDI resistance in AML.

PMID- 16304047
TI  - Macrophages from C3-deficient mice have impaired potency to stimulate
      alloreactive T cells.
AB  - Impaired T-cell reactivity is a feature of C3-deficient mice in several disease
      models. The mechanism behind the reduced T-cell response is, however, poorly
      understood. We explored the hypothesis that antigen-presenting cells (APCs) from
      C3-/- mice have impaired potency to stimulate antigen-specific T cells, in an
      alloantigen-dependent model. Our results show that C3-/- macrophages have reduced
      ability to elicit alloreactive T-cell responses in vitro and in vivo, affecting
      both the primary and secondary responses. The C3 status of donor macrophages had
      a major impact on the CD4 T-cell response. The impaired CD4 T-cell response was
      associated with reduced expression of MHC class II on the surface of C3-/-
      macrophages, without loss of class II gene expression. Furthermore, inhibition of
      C3 gene expression in C3+/+ macrophages reduced their ability to stimulate
      alloreactive T cells, suggesting that endogenous production of C3 could in part
      contribute to the potency of APCs. Our data provide compelling evidence that C3
      deficiency modulates the potency of APCs to stimulate the T-cell response,
      suggesting a critical role for complement in the maintenance of APC function.
      This could offer a partial explanation as to why the T-cell response is impaired
      in C3-/- mice.

PMID- 16304048
TI  - alphaIIbbeta3 biogenesis is controlled by engagement of alphaIIb in the calnexin
      cycle via the N15-linked glycan.
AB  - Although much is known about alphaIIbbeta3 structure and function, relatively
      little is understood about its biogenesis. Thus, we studied the kinetics of pro
      alphaIIb production and degradation, focusing on whether proteasomal degradation
      or the calnexin cycle participates in these processes. In pulse-chase analyses,
      the time to half-disappearance of pro-alphaIIb (t1/2) was the same in (1) HEK293
      cells transfected with (a) alphaIIb plus beta3, (b) alphaIIb alone, (c) mutant
      V298FalphaIIb plus beta3, or (d) I374TalphaIIb plus beta3; and (2) murine wild
      type and beta3-null megakaryocytes. Inhibition of the proteasome prolonged the
      t1/2 values in both HEK293 cells and murine megakaryocytes. Calnexin
      coprecipitated with alphaIIb from HEK293 cells transfected with alphaIIb alone,
      alphaIIb plus beta3, and V298FalphaIIb plus beta3. For proteins in the calnexin
      cycle, removal of the terminal mannose residue of the middle branch of the core N
      linked glycan results in degradation. Inhibition of the enzyme that removes this
      mannose residue prevented pro-alphaIIb degradation in beta3-null murine
      megakaryocytes. alphaIIb contains a conserved glycosylation consensus sequence at
      N15, and an N15Q mutation prevented pro-alphaIIb maturation, complex formation,
      and degradation. Our findings suggest that pro-alphaIIb engages the calnexin
      cycle via the N15 glycan and that failure of pro-alphaIIb to complex normally
      with beta3 results in proteasomal degradation.

PMID- 16304049
TI  - Expression of the DNAM-1 ligands, Nectin-2 (CD112) and poliovirus receptor
      (CD155), on dendritic cells: relevance for natural killer-dendritic cell
      interaction.
AB  - In this study, we demonstrate the involvement of DNAM-1-triggering receptor and
      its ligands, poliovirus receptor (PVR) and Nectin-2, in natural killer (NK) cell
      mediated lysis of dendritic cells (DCs). The surface expression of both ligands
      was up-regulated in DCs as compared to monocytes. It reached maximal densities
      after DC maturation induced by different stimuli including lipopolysaccharide
      (LPS), poly I:C, flagellin, and CD40L. Both immunohistochemical analysis and
      confocal microscopy revealed expression of DNAM-1 ligands by DCs in lymph nodes
      in which they were localized in the parafollicular T-cell region and surrounded
      the high endothelial venules. Remarkably, in cytolytic assays, DNAM-1 cooperated
      with NKp30 in the NK-mediated killing of both immature and mature DCs and the
      degree of contribution of DNAM-1 appeared to correlate with the surface densities
      of its specific ligands PVR and Nectin-2.

PMID- 16304050
TI  - Epigenetic processes play a major role in B-cell-specific gene silencing in
      classical Hodgkin lymphoma.
AB  - Many B-lineage-specific genes are down-regulated in Hodgkin and Reed-Sternberg
      (HRS) cells of classical Hodgkin lymphoma (cHL). We investigated the involvement
      of epigenetic modifications in gene silencing in cHL cell lines and in
      microdissected primary HRS cells. We assessed the expression and methylation
      status of CD19, CD20, CD79B, SYK, PU.1, BOB.1/OBF.1, BCMA, and LCK, all of which
      are typically down-regulated in cHL. We could reactivate gene expression in cHL
      cell lines with the DNA demethylating agent 5-aza-deoxycytidine (5-aza-dC). Using
      methylation-specific polymerase chain reaction (MSP), bisulfite genomic
      sequencing, and digestion with methylation-sensitive endonuclease followed by
      polymerase chain reaction (PCR), we determined the methylation status of promoter
      regions of PU.1, BOB.1/OBF.1, CD19, SYK, and CD79B. Down-regulation of
      transcription typically correlated with hypermethylation. Using bisulfite genomic
      sequencing we found that in microdissected HRS cells of primary cHL SYK,
      BOB.1/OBF.1, and CD79B promoters were also hypermethylated. Ectopic expression of
      both Oct2 and PU.1 in a cHL cell line potentiated endogenous PU.1 and SYK
      expression after 5-aza-dC treatment. These observations indicate that silencing
      of the B-cell-specific genes in cHL may be the consequence of a compromised
      regulatory network where down-regulation of a few master transcription factors
      results in silencing of numerous genes.

PMID- 16304052
TI  - A recombinant single-chain IL-7/HGFbeta hybrid cytokine induces juxtacrine
      interactions of the IL-7 and HGF (c-Met) receptors and stimulates the
      proliferation of CFU-S12, CLPs, and pre-pro-B cells.
AB  - A novel recombinant interleukin-7/hepatocyte growth factor beta-chain (IL
      7/HGFbeta) hybrid cytokine was constructed as a single chain (sc) composed of IL
      7 and HGFbeta connected by a flexible linker. Unlike recombinant (r) IL-7, which
      stimulated pro-B cells and pre-B cells only, scIL-7/HGFbeta stimulated the
      proliferation of pre-pro-B cells, common lymphoid progenitors (CLPs), and colony
      forming unit (CFU)-S12 in cultures of IL-7-/- mouse BM cells. When injected in
      vivo, 3- to 4-fold more splenic B-lineage cells appeared in recipients of bone
      marrow (BM) cells from the scIL-7/HGFbeta-stimulated cultures than from rIL-7
      stimulated cultures. Moreover, on a per-cell basis, scIL-7/HGFbeta culture
      generated cells produced 16- to 20-fold more BM and splenic B-lineage cells than
      did normal BM cells. Antibody blocking, receptor phosphorylation, and confocal
      microscopy demonstrated that scIL-7/HGFbeta signals though both the IL-7 and HGF
      (c-Met) receptors, which form IL-7R/c-Met complexes on the surface of CLPs and
      pre-pro-B cells. In addition, the IL-7Ralpha chain, gammac chain, and c-Met were
      coisolated from purified CLPs and pre-pro-B cells on scIL-7/HGFbeta affinity
      gels, indicating that they are major components of the IL-7/HGFbeta receptor.
      Hence, the present results demonstrate that the IL-7/HGFbeta hybrid cytokine
      efficiently and selectively stimulates the most primitive B-lineage precursors in
      BM by inducing juxtacrine interactions between the IL-7 and c-Met receptors.

PMID- 16304051
TI  - Combined deficiency of factor V and factor VIII is due to mutations in either
      LMAN1 or MCFD2.
AB  - Mutations in LMAN1 (ERGIC-53) or MCFD2 cause combined deficiency of factor V and
      factor VIII (F5F8D). LMAN1 and MCFD2 form a protein complex that functions as a
      cargo receptor ferrying FV and FVIII from the endoplasmic reticulum to the Golgi.
      In this study, we analyzed 10 previously reported and 10 new F5F8D families.
      Mutations in the LMAN1 or MCFD2 genes accounted for 15 of these families,
      including 3 alleles resulting in no LMAN1 mRNA accumulation. Combined with our
      previous reports, we have identified LMAN1 or MCFD2 mutations as the causes of
      F5F8D in 71 of 76 families. Among the 5 families in which no mutations were
      identified, 3 were due to misdiagnosis, with the remaining 2 likely carrying
      LMAN1 or MCFD2 mutations that were missed by direct sequencing. Our results
      suggest that mutations in LMAN1 and MCFD2 may account for all cases of F5F8D.
      Immunoprecipitation and Western blot analysis detected a low level of LMAN1-MCFD2
      complex in lymphoblasts derived from patients with missense mutations in LMAN1
      (C475R) or MCFD2 (I136T), suggesting that complete loss of the complex may not be
      required for clinically significant reduction in FV and FVIII.

PMID- 16304053
TI  - Essential role of PI3Kdelta and PI3Kgamma in thymocyte survival.
AB  - Class 1 phosphoinositide 3-kinases (PI3Ks), consisting of PI3Kalpha, beta, gamma,
      and delta, are a family of intracellular signaling molecules that play important
      roles in cell-mediated immune responses. In thymocytes, however, their role is
      less clear, although PI3Kgamma is postulated to partially contribute to pre-TCR
      dependent differentiation. We now report that PI3Kdelta, in conjunction with
      PI3Kgamma, is required for thymocyte survival and ultimately for T-cell
      production. Surprisingly, genetic deletion of the p110delta and p110gamma
      catalytic subunits resulted in a dramatic reduction in thymus size, cellularity,
      and lack of corticomedullary differentiation. Total thymocyte counts in these
      animals were 27-fold lower than in wild-type (WT) controls because of a
      diminished number of CD4+ CD8+ double-positive (DP) cells and were associated
      with T-cell depletion in blood and in secondary lymphoid organs. Moreover, this
      alteration in the DP population was intrinsic to thymocytes, because the
      reconstitution of p110gammadelta-/- animals with WT fetal liver cells restored
      the proportions of all thymocyte populations to those in WT controls. The
      observed defects were related to massive apoptosis in the DP population; TCRB
      expression, pre-TCR selection, and generation of DP cells appeared relatively
      unperturbed. Thus, class 1 PI3Ks work in concert to protect developing thymocytes
      from apoptosis.

PMID- 16304055
TI  - Keratinocyte growth factor (KGF) is required for postnatal thymic regeneration.
AB  - Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor
      family that mediates epithelial cell proliferation and differentiation in a
      variety of tissues, including the thymus. We studied the role of KGF in T-cell
      development with KGF-/- mice and demonstrated that thymic cellularity and the
      distribution of thymocyte subsets among KGF-/-, wildtype (WT), and KGF+/- mice
      were similar. However, KGF-/- mice are more vulnerable to sublethal irradiation
      (450 cGy), and a significant decrease was found in thymic cellularity after
      irradiation. Defective thymopoiesis and peripheral T-cell reconstitution were
      found in KGF-/- recipients of syngeneic or allogeneic bone marrow transplant, but
      using KGF-/- mice as a donor did not affect T-cell development after
      transplantation. Despite causing an early developmental block in the thymus,
      administration of KGF to young and old mice enhanced thymopoiesis. Exogenous KGF
      also accelerated thymic recovery after irradiation, cyclophosphamide, and
      dexamethasone treatment. Finally, we found that administering KGF before bone
      marrow transplantation (BMT) resulted in enhanced thymopoiesis and peripheral T
      cell numbers in middle-aged recipients of an allogeneic BM transplant. We
      conclude that KGF plays a critical role in postnatal thymic regeneration and may
      be useful in treating immune deficiency conditions.

PMID- 16304054
TI  - Role of platelet surface PF4 antigenic complexes in heparin-induced
      thrombocytopenia pathogenesis: diagnostic and therapeutic implications.
AB  - Heparin-induced thrombocytopenia (HIT) antibodies recognize complexes between
      heparin and platelet factor 4 (PF4). Heparin and PF4 bind HIT antibodies only
      over a narrow molar ratio. We explored the involvement of platelet surface-bound
      PF4 as an antigen in the pathogenesis of experimental HIT. We show that cell
      surface PF4 complexes are also antigenic only over a restricted concentration
      range of PF4. Heparin is not required for HIT antibody binding but shifts the
      concentration of PF4 needed for optimal surface antigenicity to higher levels.
      These data are supported by in vitro studies involving both human and murine
      platelets with exogenous recombinant human (h) PF4 and either an anti-PF4-heparin
      monoclonal antibody (KKO) or HIT immunoglobulin. Injection of KKO into transgenic
      mice expressing different levels of hPF4 demonstrates a correlation between the
      severity of the thrombocytopenia and platelet hPF4 expression. Therapeutic
      interventions in this model using high-dose heparin or protamine sulfate support
      the pathogenic role of surface PF4 antigenic complexes in the etiology of HIT. We
      believe that this focus on surface PF4 advances our understanding of the
      pathogenesis of HIT, suggests ways to identify patients at high risk to develop
      HIT upon heparin exposure, and offers new therapeutic strategies.

PMID- 16304056
TI  - c-FLIP confers resistance to FAS-mediated apoptosis in anaplastic large-cell
      lymphoma.
AB  - We hypothesized that inhibition of the FAS-mediated apoptosis pathway by FLICE
      like inhibitory protein (c-FLIP) may contribute to oncogenesis in ALK+ anaplastic
      large-cell lymphoma (ALCL). Treatment with increasing concentrations of CH-11
      (CD95/FAS agonistic antibody) had no effect on cell viability of 2 ALK+ ALCL cell
      lines, Karpas 299 and SU-DHL1, each expressing high levels of c-FLIP. However,
      inhibition of endogenous c-FLIP expression by specific c-FLIP siRNA in Karpas 299
      and SU-DHL1 cells treated with CH-11 resulted in FAS-mediated cell death
      associated with increased annexin V binding, apoptotic morphology, and cleavage
      of caspase-8. In 26 ALK+ ALCL tumors, assessed for expression of DISC-associated
      proteins, CD95/FAS and c-FLIP were commonly expressed, in 23 (92%) of 25 and 21
      (91%) of 23 tumors, respectively. By contrast, CD95L/FASL was expressed in only 3
      (12%) of 26 ALCL tumors, although it was strongly expressed by surrounding small
      reactive lymphocytes. Our findings suggest that overexpression of c-FLIP protects
      ALK+ ALCL cells from death-receptor-induced apoptosis and may contribute to ALCL
      pathogenesis.

PMID- 16304057
TI  - IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer
      patients.
AB  - Interleukin-2 (IL-2) is historically known as a T-cell growth factor.
      Accumulating evidence from knockout mice suggests that IL-2 is crucial for the
      homeostasis and function of CD4+ CD25+ regulatory T cells in vivo. However, the
      impact of administered IL-2 in an immune intact host has not been studied in
      rodents or humans. Here, we studied the impact of IL-2 administration on the
      frequency and function of human CD4+ CD25(hi) T cells in immune intact patients
      with melanoma or renal cancer. We found that the frequency of CD4+ CD25(hi) T
      cells was significantly increased after IL-2 treatment, and these cells expressed
      phenotypic markers associated with regulatory T cells. In addition, both
      transcript and protein levels of Foxp3, a transcription factor exclusively
      expressed on regulatory T cells, were consistently increased in CD4 T cells
      following IL-2 treatment. Functional analysis of the increased number of CD4+
      CD25(hi) T cells revealed that this population exhibited potent suppressive
      activity in vitro. Collectively, our results demonstrate that administration of
      high-dose IL-2 increased the frequency of circulating CD4+ CD25(hi) Foxp3+
      regulatory T cells. Our findings suggest that selective inhibition of IL-2
      mediated enhancement of regulatory T cells may improve the therapeutic
      effectiveness of IL-2 administration.

PMID- 16304058
TI  - Genetic variation in bactericidal/permeability-increasing protein influences the
      risk of developing rapid airflow decline after hematopoietic cell
      transplantation.
AB  - Innate immunity is involved in the biology of graft versus host disease and
      common airway diseases. We screened 15 genes in this pathway using a linkage
      disequilibrium-based approach to identify potential candidate genes that may be
      involved in the development of airflow obstruction after hematopoietic cell
      transplantation. Sixty-nine single-nucleotide polymorphisms were selected for
      assessment in a discovery cohort (n = 363). Significant associations were
      validated in a validation cohort (n = 209). Expression of the candidate gene was
      demonstrated by detecting gene transcript and protein in malignant and normal
      small airway epithelial cells. In the discovery cohort, 133 patients developed
      significant airflow decline. Four patient and donor bactericidal/permeability
      increasing (BPI) haplotypes were associated with a 2-fold to 3-fold increased
      risk of developing significant airflow decline (P values, .004-.038). This
      association was confirmed in the validation cohort, which had 66 patients with
      significant airflow decline, with 9 significant haplotypes (P values, .013-.043).
      BPI gene transcript and protein were detected in airway epithelial cells. These
      results suggest mutations in the BPI gene significantly influence the risk of
      developing rapid airflow decline after hematopoietic cell transplantation and may
      represent a novel therapeutic target for this form of airway disease.

PMID- 16304059
TI  - Endothelial protein C receptor (CD201) explicitly identifies hematopoietic stem
      cells in murine bone marrow.
AB  - The hematopoietic stem cell (HSC) is a unique cell type found in bone marrow,
      which has the capacity for both self-renewal and differentiation into all blood
      lineages. The identification of genes expressed specifically in HSCs may help
      identify gene products vital to the control of self-renewal and/or
      differentiation, as well as antigens capable of forming the basis for improved
      methods of stem cell isolation. In previous studies, we identified a number of
      genes that appeared to be differentially expressed in murine bone marrow-derived
      HSCs, using microarray technology. We report here that one of those genes,
      encoding the murine endothelial protein C receptor (EPCR), is expressed at high
      levels within the bone marrow in HSCs. Bone marrow cells isolated on the basis of
      EPCR expression alone are highly enriched for hematopoietic reconstitution
      activity, showing levels of engraftment in vivo comparable to that of stem cells
      purified using the most effective conventional methods. Moreover, evaluation of
      cell populations first enriched for stem cell activity by conventional methods
      and subsequently fractionated on the basis of EPCR expression indicates that stem
      cell activity is always associated with EPCR-expressing cells. Based on our
      findings, we believe EPCR represents the first known marker that 'explicitly'
      identifies hematopoietic stem cells within murine bone marrow.

PMID- 16304060
TI  - Angiotensin II-stimulated signaling through G proteins and beta-arrestin.
AB  - Beta-arrestin, originally identified as a protein that inhibits heterotrimeric
      guanine nucleotide-binding protein (G protein) coupling to cognate seven
      transmembrane receptors [(7TMRs), also known as G protein-coupled receptors
      (GPCRs)], is currently being appreciated as a positive signaling mediator for
      various cell surface receptors. Activation of mitogen-activated protein kinases
      (MAPKs), especially extracellular signal regulated kinases 1 and 2 (ERK1/2), is a
      hallmark of intracellular signaling resulting from stimulation of various growth
      factor receptors, as well as 7TMRs. The resulting ERK activity can occur through
      multiple parallel or converging mechanisms. Using human embryonic kidney 293 (HEK
      293) cells as a model system and utilizing RNA interference technology, two
      distinct pathways of angiotensin II-mediated ERK activation have been uncovered:
      (i) a G protein-dependent pathway that produces a transient activation of nuclear
      ERK and (ii) a beta-arrestin-dependent pathway that leads to sustained activation
      of ERK that is localized to the cytosol and endosomes. The spatial and temporal
      segregation of ERK activated by G protein and beta-arrestin pathways suggests
      that the physiological consequences may be different, and thus ligands that
      selectively stimulate or inhibit one of these pathways may be therapeutically
      valuable.

PMID- 16304061
TI  - The cover. As the old ones sing, so the young ones pipe.

PMID- 16304062
TI  - A piece of my mind. Malignant neglect.

PMID- 16304063
TI  - Advances aim to ease stem cell concerns.

PMID- 16304064
TI  - Experts: target heart disease from birth.

PMID- 16304065
TI  - Kidney failure rates end 20-year climb.

PMID- 16304066
TI  - Conflicts of interest and independent data analysis in industry-funded studies.

PMID- 16304067
TI  - Conflicts of interest and independent data analysis in industry-funded studies.

PMID- 16304068
TI  - Severe malnutrition assessment in children in rural Kenya.

PMID- 16304069
TI  - Iatrogenic risk of screening for youth suicide.

PMID- 16304070
TI  - Insulin resistance and congestive heart failure.

PMID- 16304071
TI  - "Manufacturing vs repair" in health care.

PMID- 16304072
TI  - Risk of pelvic fractures in older women following pelvic irradiation.
AB  - CONTEXT: Pelvic fractures, including hip fractures, are a major source of
      morbidity and mortality in older women. Although therapeutic pelvic irradiation
      could increase the risk of such fractures, this effect has not been studied.
      OBJECTIVE: To determine if women who undergo pelvic irradiation for pelvic
      malignancies (anal, cervical, or rectal cancers) have a higher rate of pelvic
      fracture than women with pelvic malignancies who do not undergo irradiation.
      DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study
      using Surveillance, Epidemiology, and End Results (SEER) cancer registry data
      linked to Medicare claims data. A total of 6428 women aged 65 years and older
      diagnosed with pelvic malignancies from 1986 through 1999 were included. We
      compared results for women who did (n = 2855) vs did not (n = 3573) undergo
      radiation therapy. To assess the influence of selection bias, we also evaluated
      the effect of irradiation on osteoporotic fractures in nonirradiated sites (arm
      and spine). MAIN OUTCOME MEASURE: We evaluated the effect of irradiation on the
      incidence of pelvic fractures over time, and adjusted for potential confounders
      using a proportional hazards model. RESULTS: Women who underwent radiation
      therapy were more likely to have a pelvic fracture than women who did not undergo
      radiation therapy (cumulative 5-year fracture rate, 14.0% vs 7.5% in women with
      anal cancer, 8.2% vs 5.9% in women with cervical cancer, and 11.2% vs 8.7% in
      women with rectal cancer); the difference was statistically significant and most
      fractures (90%) were hip fractures. We controlled for potential confounders
      including age, race, cancer stage, and geographic location. The impact of
      irradiation varied by cancer site: treatment for anal cancer was associated with
      a higher risk of pelvic fractures (hazard ratio, 3.16; 95% confidence interval,
      1.48-6.73); than for cervical cancer (hazard ratio, 1.66; 95% confidence
      interval, 1.06-2.59); or rectal cancer (hazard ratio, 1.65; 95% confidence
      interval, 1.33-2.05). No statistically significant difference was found in the
      rate of arm or spine fractures between the irradiated and nonirradiated groups
      (hazard ratio, 1.15; 95% confidence interval, 0.89-1.48). CONCLUSIONS: Pelvic
      irradiation substantially increases the risk of pelvic fractures in older women.
      Given the high baseline risk of pelvic fracture, this finding is of particular
      concern.

PMID- 16304073
TI  - High-risk patients with acute coronary syndromes treated with low-molecular
      weight or unfractionated heparin: outcomes at 6 months and 1 year in the SYNERGY
      trial.
AB  - CONTEXT: The SYNERGY trial comparing enoxaparin and unfractionated heparin in
      high-risk patients with acute coronary syndromes (ACS) showed that enoxaparin was
      not inferior to unfractionated heparin in reducing death or nonfatal myocardial
      infarction (MI) at 30 days. OBJECTIVE: To evaluate continued risk in this patient
      cohort through 6-month and 1-year follow-up. DESIGN, SETTING, AND PATIENTS:
      Overall, 9978 patients were randomized from August 2001 through December 2003 in
      487 hospitals in 12 countries. Patients were followed up for 6 months and for 1
      year. MAIN OUTCOME MEASURES: Six-month outcomes were death, nonfatal MI,
      revascularization procedures, stroke, and site-investigator-reported need for
      rehospitalization; 1-year outcome was all-cause death. RESULTS: Six-month and 1
      year follow-up data were available for 9957 (99.8%) and 9608 (96.3%) of 9978
      patients, respectively; 541 patients (5.4%) had died at 6 months and 739 (7.4%)
      at 1 year. Death or nonfatal MI at 6 months occurred in 872 patients receiving
      enoxaparin (17.6%) vs 884 receiving unfractionated heparin (17.8%) (hazard ratio
      [HR], 0.98; 95% confidence interval [CI], 0.89-1.07; P = .65). In the subgroup of
      patients receiving consistent therapy, ie, only enoxaparin or unfractionated
      heparin during the index hospitalization (n = 6138), a reduction in death or
      nonfatal MI with enoxaparin was maintained at 180 days (HR, 0.85; 95% CI, 0.75
      0.95; P = .006). Rehospitalization within 180 days occurred in 858 patients
      receiving enoxaparin (17.9%) and 911 receiving unfractionated heparin (19.0%)
      (HR, 0.94; 95% CI, 0.85-1.03; P = .17). One-year all-cause death rates were
      similar in the 2 treatment groups (380/4974 [7.6%] for enoxaparin vs 359/4948
      [7.3%] for unfractionated heparin; HR, 1.06; 95% CI, 0.92-1.22; P = .44). One
      year death rates in patients receiving consistent therapy were also similar
      (251/3386 [7.4%] for enoxaparin vs 213/2720 [7.8%] for unfractionated heparin;
      HR, 0.95; 95% CI, 0.79-1.14; P = .55). CONCLUSIONS: In the SYNERGY trial,
      patients continued to experience adverse cardiac events through long-term follow
      up. The effect of enoxaparin on death or MI compared with that of unfractionated
      heparin at 6 months was similar to that observed at 30 days in the overall trial
      and in the consistent-therapy group. One-year death rates were also similar in
      both groups. High-risk patients with ACS remain susceptible to continued cardiac
      events despite aggressive therapies.ClinicalTrials.gov Identifier: NCT00043784.

PMID- 16304074
TI  - Duration of lactation and incidence of type 2 diabetes.
AB  - CONTEXT: Lactation is associated with improved glucose and insulin homeostasis,
      independent of weight change. OBJECTIVE: To evaluate the association between
      lactation history and incidence of type 2 diabetes. DESIGN, SETTING, AND
      PARTICIPANTS: Prospective observational cohort study of 83,585 parous women in
      the Nurses' Health Study (NHS) and retrospective observational cohort study of
      73,418 parous women in the Nurses' Health Study II (NHS II). MAIN OUTCOME
      MEASURE: Incident cases of type 2 diabetes mellitus. RESULTS: In the NHS, 5145
      cases of type 2 diabetes were diagnosed during 1,239,709 person-years of follow
      up between 1986 and 2002, and in the NHS II, 1132 cases were diagnosed during
      778,876 person-years of follow-up between 1989 and 2001. Among parous women,
      increasing duration of lactation was associated with a reduced risk of type 2
      diabetes. For each additional year of lactation, women with a birth in the prior
      15 years had a decrease in the risk of diabetes of 15% (95% confidence interval,
      1%-27%) among NHS participants and of 14% (95% confidence interval, 7%-21%) among
      NHS II participants, controlling for current body mass index and other relevant
      risk factors for type 2 diabetes. CONCLUSIONS: Longer duration of breastfeeding
      was associated with reduced incidence of type 2 diabetes in 2 large US cohorts of
      women. Lactation may reduce risk of type 2 diabetes in young and middle-aged
      women by improving glucose homeostasis.

PMID- 16304075
TI  - Hospital characteristics associated with the management of pediatric splenic
      injuries.
AB  - CONTEXT: Despite evidence that more than 90% of children with traumatic injuries
      to the spleen can be successfully managed nonoperatively, there is significant
      variation in the use of splenectomy. As asplenic children are at increased risk
      of overwhelming postsplenectomy infection, nonoperative management may be
      considered a quality of care indicator. OBJECTIVE: To test the hypothesis that
      children are more likely to undergo splenectomy in general hospitals than in
      children's hospitals. DESIGN: Retrospective cohort study using data from the
      Kid's Inpatient Database (KID) for the year 2000. Multivariable regression was
      used to control for patient and hospital characteristics. SETTING AND
      PARTICIPANTS: All children aged 0 to 16 years who were hospitalized with a
      traumatic (noniatrogenic) spleen injury in nonfederal short-stay hospitals in any
      of the 27 states participating in KID (N = 2851). MAIN OUTCOME MEASURE:
      Splenectomy performed within 1 day of arrival. RESULTS: A total of 11 children
      (3%) with splenic injuries receiving care at children's hospitals underwent
      splenectomy compared with 383 children (15.4%) cared for at general hospitals
      (P<.001). After adjusting for patient characteristics, injury severity, and
      hospital characteristics, splenectomy was more likely among children treated at
      general hospitals (odds ratio, 5.01; 95% confidence interval, 2.21-11.36) than
      among children treated at children's hospitals. CONCLUSIONS: There is
      considerable variation in the management of pediatric splenic injuries, with
      significantly lower rates of splenectomy at designated children's hospitals.
      Quality improvement interventions, including increased education and training for
      physicians in general hospitals, may be needed to increase the use of spleen
      conserving management practices.

PMID- 16304076
TI  - Quality, innovation, and value for money: NICE and the British National Health
      Service.
AB  - The National Institute for Health and Clinical Excellence (NICE) was established
      as a part of the British National Health Service in 1999 to set standards for the
      adoption of new health care technologies and the management of specific
      conditions. In doing so it was required explicitly to take into account both
      clinical effectiveness and cost-effectiveness. This article describes how NICE
      has responded to the challenge and considers whether its experience of balancing
      quality, innovation, and value for money holds policy lessons for the United
      States.

PMID- 16304077
TI  - Value and limitations of chest pain history in the evaluation of patients with
      suspected acute coronary syndromes.
AB  - CONTEXT: The chest pain history, physical examination, determination of coronary
      artery disease (CAD) risk factors, and the initial electrocardiogram compose the
      information immediately available to clinicians to help determine the probability
      of acute myocardial infarction (AMI) or acute coronary syndrome (ACS) in patients
      with chest pain. However, conflicting data exist about the usefulness of the
      chest pain history and which components are most useful. OBJECTIVE: To identify
      the elements of the chest pain history that may be most helpful to the clinician
      in identifying ACS in patients presenting with chest pain. EVIDENCE ACQUISITION:
      MEDLINE and Ovid were searched from 1970 to September 2005 by using specific key
      words and Medical Subject Heading terms. Reference lists of these articles and
      current cardiology textbooks were also consulted. EVIDENCE SYNTHESIS: Certain
      chest pain characteristics decrease the likelihood of ACS or AMI, namely, pain
      that is stabbing, pleuritic, positional, or reproducible by palpation (likelihood
      ratios [LRs] 0.2-0.3). Conversely, chest pain that radiates to one shoulder or
      both shoulders or arms or is precipitated by exertion is associated with LRs (2.3
      4.7) that increase the likelihood of ACS. The chest pain history itself has not
      proven to be a powerful enough predictive tool to obviate the need for at least
      some diagnostic testing. Combinations of elements of the chest pain history with
      other initially available information, such as a history of CAD, have identified
      certain groups that may be safe for discharge without further evaluation, but
      further study is needed before such a recommendation can be considered
      reasonable. CONCLUSION: Although certain elements of the chest pain history are
      associated with increased or decreased likelihoods of a diagnosis of ACS or AMI,
      none of them alone or in combination identify a group of patients that can be
      safely discharged without further diagnostic testing.

PMID- 16304078
TI  - Drug prices and value for money: the Australian Pharmaceutical Benefits Scheme.

PMID- 16304079
TI  - Postradiotherapy pelvic fractures: cause for concern or opportunity for future
      research?

PMID- 16304080
TI  - JAMA patient page. The spleen.

PMID- 16304081
TI  - Added value of SPECT/CT fusion in assessing suspected bone metastasis: comparison
      with scintigraphy alone and nonfused scintigraphy and CT.
AB  - PURPOSE: To evaluate retrospectively if there is additional diagnostic value of
      fused single photon emission computed tomographic (SPECT) and computed
      tomographic (CT) images in assessing possible bone metastases. MATERIALS AND
      METHODS: Institutional review board approval was obtained, and each patient
      provided written informed consent. Bone scintigraphy--including planar and SPECT
      imaging-and CT were performed with a combined SPECT/CT system in 45 oncologic
      patients (24 men, 21 women; mean age, 64.7 years +/- 8.7), with a total of 42
      metastatic bone foci and 40 benign foci. The reference standard was follow-up
      radiologic imaging. Two independent readers first analyzed only bone
      scintigraphic images and next analyzed two separate sets of bone scintigraphic
      and CT images. They then analyzed bone scintigraphic, CT, and fused images and
      focused on the additional value of fused images. Diagnostic confidence for each
      lesion was scored. The three analyses were performed 7 days apart, and the images
      were presented in random order at each session. The value of additional fused
      images was assessed by using receiver operating characteristic analysis. RESULTS:
      After review of fused images to classify indeterminate lesions, reviewer 1 became
      more confident in diagnosis of the 15 benign lesions and two metastases, and
      reviewer 2 became more confident in diagnosis of the seven benign lesions and one
      metastasis. The area under the receiver operating characteristic curve for
      reviewer 1 was 0.589 for scintigraphic images, 0.831 for separate data sets of
      scintigraphic and CT images, and 0.947 for fused images. The corresponding areas
      under the receiver operating characteristic curve for reviewer 2 were 0.771,
      0.885, and 0.968, respectively. CONCLUSION: Results demonstrate the increased
      diagnostic confidence obtained with fused SPECT/CT images compared with separate
      sets of scintigraphic and CT images in differentiating malignant from benign bone
      lesions.

PMID- 16304082
TI  - Chlamydia pneumoniae: comparison with findings of Mycoplasma pneumoniae and
      Streptococcus pneumoniae at thin-section CT.
AB  - PURPOSE: To retrospectively compare thin-section computed tomographic (CT)
      findings of Chlamydia pneumoniae pneumonia with those of Streptococcus pneumoniae
      pneumonia and Mycoplasma pneumoniae pneumonia. MATERIALS AND METHODS:
      Institutional review board and patient informed consent were not required. Twenty
      four patients with C pneumoniae pneumonia (17 men, seven women; age range, 19-89
      years) underwent thin-section CT; 41 patients with S pneumoniae pneumonia (28
      men, 13 women; age range, 19-91 years) and 30 patients with M pneumoniae
      pneumonia (20 men, 10 women; age range, 16-67 years) were also enrolled. Thin
      section CT scans of each patient were retrospectively and independently assessed
      by two chest radiologists for consolidation, ground-glass opacity (GGO),
      bronchovascular bundle thickening, nodules, pleural effusion, lymphadenopathy,
      reticular or linear opacity, airway dilatation, pulmonary emphysema, and
      bilateral lung involvement. Consensus was reached for disagreements. The
      frequency of each finding was compared among the three types of pneumonia by
      using the chi2 test. RESULTS: For C pneumoniae pneumonia, CT demonstrated
      consolidation in 20 patients, GGO in 13, bronchovascular bundle thickening in 17,
      nodules in 18, pleural effusion in six, lymphadenopathy in eight, reticular or
      linear opacity in 15, airway dilatation in nine, pulmonary emphysema in 11, and
      bilateral lung involvement in 12. Bronchovascular bundle thickening (P = .022)
      and airway dilatation (P = .034) were significantly more frequent in patients
      with C pneumoniae pneumonia than in those with S pneumoniae pneumonia. Reticular
      or linear opacity (P = .017), airway dilatation (P = .016), and associated
      pulmonary emphysema (P = .003) were significantly more frequent in patients with
      C pneumoniae pneumonia than in those with M pneumoniae pneumonia. CONCLUSION: C
      pneumoniae pneumonia demonstrates a wide spectrum of thin-section CT findings
      that are similar to those of S pneumoniae pneumonia and M pneumoniae pneumonia;
      airway dilatation and bronchovascular thickening were significantly more frequent
      in patients with C pneumoniae pneumonia.

PMID- 16304083
TI  - Atherosclerotic disease: whole-body cardiovascular imaging with MR system with 32
      receiver channels and total-body surface coil technology--initial clinical
      results.
AB  - In this prospective study, the feasibility of a comprehensive cardiovascular
      imaging protocol with a dedicated whole-body 1.5-T magnetic resonance (MR) imager
      with 32 receiver channels in 34 patients with peripheral arterial occlusive
      disease was evaluated. Informed consent and institutional review board approval
      were obtained. Three-dimensional MR angiographic data sets were acquired with
      adapted injection protocol. Cardiac functional imaging and delayed-enhancement
      imaging were performed, as were fluid-attenuated inversion-recovery imaging of
      the brain and time-of-flight MR angiography of the intracranial blood vessels.
      Sensitivity and specificity for depiction of significant vascular stenosis (>
      70%) were 96%, with conventional digital subtraction angiography as the standard.
      Substantial microangiopathic tissue alterations (n = 4) and/or cerebral
      infarction (n = 4) were diagnosed in seven patients. In seven patients,
      subendocardial or transmural delayed enhancement was detected in corresponding
      regions, indicating prior myocardial infarction. Previously unknown findings
      diagnosed with MR imaging required midterm follow-up or therapy in 24 patients,
      whereas change of therapy or immediate treatment was necessary in three. For
      patients suspected of having systemic atherosclerotic disease, comprehensive risk
      assessment is feasible within 30 minutes.

PMID- 16304084
TI  - Material-dependent activation in prefrontal cortex: working memory for letters
      and texture patterns--initial observations.
AB  - PURPOSE: To prospectively evaluate whether a distinction between verbal and
      nonverbal short-term memory systems, as predicted with the multicomponent working
      memory model, is reflected in the material-specific patterns of activation in the
      prefrontal cortex. MATERIALS AND METHODS: Informed written consent was obtained
      from all participants, and the institutional review board approved the study
      protocol. Echo-planar MR imaging was performed in 12 healthy subjects (five
      female and seven male subjects), with a mean age of 23.52 years +/- 2.52
      (standard deviation) and a range of 20-29 years. A two-back task was used in the
      verbal and nonverbal versions. In the first version, letters were used as
      stimuli, and in the second version, the stimuli were abstract texture patterns.
      Timing parameters for both versions were the same. Statistical analysis of the
      functional data involved a fixed-effects general linear model. Regions of
      activation were identified from specific t-statistic contrasts between baseline
      and active tasks (corrected for whole-brain multiple comparisons). RESULTS: The
      following suprathreshold voxels for the verbal condition were observed
      predominantly in the left hemisphere (middle frontal gyrus, precentral gyrus,
      middle temporal gyrus, and occipital cortex). Bilateral activations were in
      inferior frontal gyri, insulae inferior, superior parietal lobules, and cingulate
      gyri. In the nonverbal condition, suprathreshold voxels were located mostly
      bilaterally in the following regions: inferior, middle, and medial frontal gyri
      and inferior parietal lobules. Active regions were also found in the precentral
      gyrus and precuneate gyrus in the left parietal lobe and the occipital cortex in
      the right hemisphere. CONCLUSION: Results of this study are consistent with the
      multicomponent model of working memory.

PMID- 16304085
TI  - Diffusion-weighted MR imaging sequence in the detection of postoperative
      recurrent cholesteatoma.
AB  - PURPOSE: To prospectively evaluate a fast spin-echo (SE) diffusion-weighted
      sequence for magnetic resonance (MR) imaging of recurrent cholesteatoma in
      patients who have undergone middle ear surgery. MATERIALS AND METHODS: The study
      was approved by the institutional review board, and informed consent was obtained
      from all patients. Twenty-four patients (10 female and 14 male patients; mean
      age, 44 years) who had undergone resection of cholesteatoma were referred for MR
      imaging. MR imaging was performed with a 1.5-T unit by using unenhanced diffusion
      weighted fast SE imaging at b factors of 0 and 800 sec/mm(2), unenhanced T2
      weighted fast SE imaging, unenhanced T1-weighted SE imaging, and delayed contrast
      material-enhanced T1-weighted imaging. Two radiologists evaluated the diffusion
      weighted fast SE images for the presence of a high-signal-intensity
      cholesteatoma. Results from MR imaging were compared with reports from second- or
      third-look surgery. Interobserver agreement was assessed with the kappa
      statistic. RESULTS: A recurrent cholesteatoma was correctly identified in 13 of
      14 patients with diffusion-weighted fast SE images obtained with a b factor of
      800 sec/mm(2), for a positive predictive value of 93%. In patients without
      recurrent cholesteatoma, all diffusion-weighted fast SE MR images obtained with a
      b factor of 800 sec/mm(2) were correctly interpreted as showing no high signal
      intensity. Thus, the negative predictive value was 100%. Sensitivity and
      specificity were 100% (13 of 13 patients) and 91% (10 of 11 patients),
      respectively. Interobserver agreement was excellent (kappa = 0.92). The smallest
      recurrent cholesteatoma was 5 mm in diameter, and this was correctly detected
      with the diffusion-weighted fast SE sequence. CONCLUSION: Diffusion-weighted fast
      SE imaging enables the depiction of recurrent cholesteatoma in patients who have
      undergone middle ear surgery.

PMID- 16304086
TI  - Type B Niemann-Pick disease: findings at chest radiography, thin-section CT, and
      pulmonary function testing.
AB  - PURPOSE: To evaluate findings at radiography, computed tomography (CT), and
      pulmonary function testing in patients with type B Niemann-Pick disease.
      MATERIALS AND METHODS: The study was approved by the institutional review board
      or ethics committee at each study site and was compliant with HIPAA at the U.S.
      site. Written informed consent was obtained from each patient or guardian and
      minor assent was obtained from all children before any study-related procedures.
      Pulmonary involvement in 53 patients (27 male and 26 female patients; age range,
      7-65 years; mean age, 23.3 years) with type B Niemann-Pick disease was evaluated
      with imaging and pulmonary function tests. All patients underwent chest
      radiography and thin-section CT, and images were independently interpreted by one
      of two radiologists. Spirometry (forced vital capacity [FVC] and forced
      expiratory volume in 1 second [FEV1]) was performed and diffusing capacity of
      lung for carbon monoxide (Dlco) was evaluated in all patients who could comply. A
      score for the degree of interstitial lung disease was derived at both radiography
      and CT, and the CT scores were then compared with results of pulmonary function
      testing and patient age by means of linear regression. CT scores were compared
      between the upper and lower lung zones by using the Wilcoxon signed rank test.
      RESULTS: Chest radiography and CT, respectively, revealed interstitial lung
      disease in 47 (90%) and 51 (98%) of the 52 patients who completed both imaging
      examinations. There was a basilar predominance of interstitial lung disease at
      CT. Six patients had pulmonary nodules, one of which was calcified at chest
      radiography. There were no statistically significant correlations between
      interstitial lung disease score at CT and age or percentage predicted FVC, FEV1,
      or Dlco values. CONCLUSION: Although pulmonary function test indexes may be
      abnormal, imaging findings do not necessarily correlate with pulmonary function
      in patients with type B Niemann-Pick disease.

PMID- 16304087
TI  - Esophageal varices: evaluation with transesophageal MR imaging--initial
      experience.
AB  - PURPOSE: To prospectively use transesophageal magnetic resonance (MR) imaging to
      determine the morphologic and hemodynamic characteristics of esophageal varices.
      MATERIALS AND METHODS: The study was approved by the ethics committee. All
      patients gave written informed consent. Forty-two patients (29 men, 13 women;
      mean age, 58 years +/- 11 [standard deviation]) with esophageal varices that were
      recently demonstrated at endoscopy were included in the study. MR imaging was
      performed by using a receiver probe that was placed in the esophagus. Black-blood
      T2-weighted MR images were obtained with cardiac triggering and navigator gating
      of the right hemidiaphragm. On these images, the maximal diameter, minimal
      diameter, and surface area of the largest esophageal varix were measured.
      Periesophageal and paraesophageal varices were recorded. A hemodynamic
      examination was performed in the last 21 patients to undergo MR imaging, which
      was used to obtain measurements of flow velocity and rate before and after
      intravenous injection of 50 mug of octreotide or a placebo. A Kruskal-Wallis test
      was used to assess differences in the diameter and surface area of the varices
      according to endoscopic grade. Hemodynamic changes observed after octreotide or
      placebo injection were compared by using an analysis of variance and a 95%
      confidence interval. RESULTS: Periesophageal varices were observed in 36
      patients, and paraesophageal varices were observed in 32 patients. The minimal
      diameter, maximal diameter, and surface area of the esophageal varices at MR
      imaging differed significantly according to endoscopic grade (P < .001). In the
      periesophageal varices, the velocity and flow changes caused by octreotide
      differed significantly from those caused by the placebo (P < .001). A decrease in
      velocity (mean velocity change, -2.766 cm.sec(-1)) and flow (mean flow change, 
      0.455 mL.sec(-1)) was noted after octreotide injection, but no significant change
      in velocity (mean velocity change, 0.252 cm.sec(-1)) or flow (mean flow change,
      0.018 mL.sec(-1)) was noted after placebo injection. The surface area of the
      varices did not change significantly after octreotide (mean change, -0.771 mm2)
      or placebo (mean change, -0.015 mm2) injection. CONCLUSION: Transesophageal MR
      imaging is a feasible method to assess the morphologic and hemodynamic
      characteristics of esophageal varices before and after pharmacologic treatment.

PMID- 16304088
TI  - Colorectal polyps: detection with dark-lumen MR colonography versus conventional
      colonoscopy.
AB  - PURPOSE: To prospectively compare dark-lumen magnetic resonance (MR) colonography
      with conventional colonoscopy in the detection of colorectal polyps. MATERIALS
      AND METHODS: Local ethical committee approval and informed consent were obtained.
      One hundred consecutive patients (56 men, 44 women; mean age +/- standard
      deviation, 67.7 years +/- 14.7; range, 25-82 years) who were referred for
      conventional colonoscopy from January 2003 to January 2004 underwent MR
      colonography and conventional colonoscopy after standard precolonoscopic bowel
      cleansing. Colonoscopy was performed immediately after MR colonography. For MR
      colonography, the colon was filled with approximately 2000 mL of tap water.
      Imaging was performed with a 1.5-T MR unit with patients in the prone position. A
      T1-weighted three-dimensional volumetric interpolated breath-hold sequence was
      performed before and 75 seconds after intravenous administration of 0.2 mmol
      gadobenate dimeglumine per kilogram of body weight. Results of MR colonography
      were analyzed on a per-polyp and per-patient basis. Findings at colonoscopy were
      used as the reference for determining accuracy, sensitivity, specificity, and
      positive and negative predictive values of MR colonography. RESULTS: Of 100
      patients recruited for study, 92 (52 men, 40 women; mean age, 61.5 years +/-
      14.5; range, 25-82 years) underwent complete MR and conventional colonoscopy
      examinations. Forty-three of the 92 patients (47%) had normal findings at
      conventional colonoscopy. In the other 49 patients (53%), conventional
      colonoscopy depicted 107 polyps (82 adenomas, 25 hyperplastic polyps) and seven
      carcinomas. At per-polyp analysis, sensitivity of MR colonography in the
      detection of adenomatous polyps was 100% for polyps at least 10 mm in diameter
      and 84.2% for polyps 6-9 mm in diameter. At per-patient analysis, the accuracy of
      MR colonography was 93.1% (sensitivity, 89%; specificity, 96%) if detection of
      adenomatous polyps of all sizes was considered. CONCLUSION: Dark-lumen MR
      colonography is a promising modality with high accuracy for detecting colorectal
      polyps larger than 5 mm in diameter.

PMID- 16304089
TI  - Delayed-phase dynamic CT enhancement as a prognostic factor for mass-forming
      intrahepatic cholangiocarcinoma.
AB  - PURPOSE: To retrospectively determine whether the degree of contrast material
      enhancement at delayed-phase dynamic computed tomography (CT) for intrahepatic
      cholangiocarcinoma (ICC) is related to the patient's prognosis after surgery.
      MATERIALS AND METHODS: Neither institutional review board approval nor informed
      consent was required for this retrospective evaluation. Thirty-two patients (22
      men, 10 women; mean age, 60.8 years; range, 33-80 years) with mass-forming ICC
      underwent dynamic CT. Delayed CT images obtained 4-6 minutes after the injection
      of contrast material were evaluated by two radiologists. Patients were classified
      in consensus into one of two groups: Group 1 included those in whom more than two
      thirds of the tumor showed enhancement on delayed-phase scans. Group 2 included
      those in whom less than two-thirds of the tumor showed enhancement on delayed
      phase scans. The imaging findings were correlated with pathologic findings.
      Survival curves were drawn by using the Kaplan-Meier method, and the differences
      between the groups were compared with the log-rank test. Multivariate analysis
      was performed to clarify prognostic factors. RESULTS: There were 13 patients in
      group 1 and 19 in group 2. The degree of enhancement on the delayed-phase images
      showed statistically significant correlation with the amount of fibrous stroma (P
      < .001) and the frequency of perineural invasion (P < .01). The survival rate in
      group 1 was significantly lower than that in group 2 (P = .016). Multivariate
      analysis revealed that enhancement of more than two-thirds of the ICC was a
      significant and independent prognostic factor. CONCLUSION: The degree of
      enhancement on delayed-phase CT scans is a useful indicator for prediction of the
      prognosis of patients with mass-forming ICC.

PMID- 16304090
TI  - Lymph node metastasis in patients with clinical early-stage cervical cancer:
      detection with integrated FDG PET/CT.
AB  - PURPOSE: To prospectively determine the accuracy of combination positron emission
      tomography-computed tomography (PET/CT) in lymph node staging in patients with
      early-stage cervical cancer, with histopathologic results as the reference
      standard. MATERIALS AND METHODS: The study was institutional review board
      approved, and all patients gave informed consent. Forty-seven consecutive women
      aged 29-71 years with clinical stage IA or IB cervical carcinoma were included in
      the study. All 47 patients were scheduled for radical hysterectomy with pelvic
      lymph node dissection. Before surgery, all patients underwent fluorine 18
      fluorodeoxyglucose (FDG) PET/CT. PET/CT findings were interpreted by two readers
      in consensus and then compared with histopathologic results. At histopathologic
      examination, the dissected lymph nodes were classified as nonmetastatic or
      metastatic. RESULTS: Fifteen (32%) patients had metastatic lymph nodes at
      histopathologic examination, and 32 (68%) had no histopathologically confirmed
      nodal metastasis. Of the total 1081 lymph nodes histopathologically sampled, 18
      were found to be positive for malignant cells. The overall node-based
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV), and accuracy of PET/CT were 72% (13 of 18), 99.7% (1060 of 1063),
      81% (13 of 16), 99.5% (1060 of 1065), and 99.3% (1073 of 1081), respectively.
      Corresponding values for PET/CT-based diagnosis of lymph nodes larger than 0.5 cm
      in diameter were 100% (13 of 13), 99.6% (675 of 678), 81% (13 of 16), 100% (675
      of 675), and 99.6% (688 of 691), respectively. The overall patient-based
      sensitivity, specificity, PPV, NPV, and accuracy of PET/CT were 73% (11 of 15),
      97% (31 of 32), 92% (11 of 12), 89% (31 of 35), and 89% (42 of 47), respectively.
      CONCLUSION: PET/CT proved to be valuable for lymph node staging in patients with
      early-stage cervical cancer, with short-axis diameter greater than 0.5 cm being
      the size threshold for accurate depiction of metastatic nodes.

PMID- 16304091
TI  - Prostate cancer: local staging at 3-T endorectal MR imaging--early experience.
AB  - PURPOSE: To prospectively investigate the local staging accuracy of 3-T
      endorectal magnetic resonance (MR) imaging for prostate cancer by using whole
      mount-section histopathologic analysis as the standard of reference. MATERIALS
      AND METHODS: This study was approved by the institutional review board, and
      informed consent was obtained from all patients. In 35 consecutive patients
      (median age, 62.3 years) with biopsy-proved prostate cancer, 3-T endorectal MR
      imaging was performed. High-spatial-resolution endorectal T2-weighted fast spin
      echo images of the prostate were obtained in three planes. MR images were
      prospectively evaluated by two experienced radiologists and a third radiologist
      who was less experienced with regard to local disease extent by using five
      established extracapsular criteria. Whole-mount-section histopathologic analysis
      was the standard of reference. Evaluation was performed according to octant and
      patient. Sensitivity, specificity, positive and negative predictive values,
      overall accuracy, and interobserver agreement were calculated. RESULTS: Thirty
      two patients who underwent radical prostatectomy were enrolled in this study.
      Accuracy, sensitivity, and specificity of local staging were 94% (30 of 32), 88%
      (seven of eight), and 96% (23 of 24), respectively, for both experienced
      radiologists, and these values were 81% (26 of 32), 50% (four of eight), and 92%
      (22 of 24), respectively, for the less experienced radiologist. There was
      substantial agreement between both experienced readers (kappa = 0.42-0.79) and
      moderate agreement between the less experienced reader and the experienced
      readers with respect to all extracapsular criteria. In regard to the three cases
      of minimal capsular invasion, two were detected by both experienced radiologists.
      CONCLUSION: In this study, high accuracy for staging of prostate cancer at 3-T
      endorectal MR imaging, with moderate to substantial observer agreement, was
      demonstrated. In addition, minimal capsular invasion could be detected.

PMID- 16304092
TI  - Biliary ductal evaluation of hilar cholangiocarcinoma: three-dimensional direct
      multi-detector row CT cholangiographic findings versus surgical and pathologic
      results--feasibility study.
AB  - The study was conducted, with institutional review board approval and informed
      patient consent, to assess the feasibility and diagnostic effectiveness of three
      dimensional direct multi-detector row computed tomographic (CT) cholangiography
      for determining the extent of bile duct invasion by hilar cholangiocarcinoma.
      Eleven patients underwent contrast material-enhanced direct multi-detector row CT
      cholangiography of the primary and secondary biliary confluence levels and then
      surgical resection. In most patients, CT cholangiography was tolerable and
      yielded excellent or good opacification of the biliary tree. CT cholangiography
      enabled a correct diagnosis of the extent of ductal involvement at all 11 primary
      confluence levels and at 18 of the 19 secondary confluence levels. Three
      secondary confluences, which could not be analyzed owing to nonopacification or
      poor opacification, proved to be involved by hilar cholangiocarcinoma. The
      authors conclude that three-dimensional direct multi-detector row CT
      cholangiography is accurate and feasible for defining the extent of ductal
      invasion by hilar cholangiocarcinoma, especially in patients with preliminary
      biliary drainage.

PMID- 16304093
TI  - MR imaging-guided 9-gauge vacuum-assisted core-needle breast biopsy: initial
      experience.
AB  - PURPOSE: To perform magnetic resonance (MR) imaging-compatible vacuum-assisted 9
      gauge core-needle biopsy of suspicious enhancing breast lesions identified at MR
      imaging. MATERIALS AND METHODS: The institutional review board granted exempt
      status for this HIPAA-compliant study and waived the requirement for informed
      consent. The MR imaging-guided 9-gauge vacuum-assisted core-needle biopsy
      findings of 85 lesions in 75 patients aged 31-89 years were retrospectively
      reviewed. The biopsies were performed as part of the patients' clinical care with
      a Food and Drug Administration-approved biopsy system and not within a research
      protocol. All included patients had received a diagnosis of malignant, benign, or
      high-risk (for cancer) breast tissue at core-needle biopsy and had undergone
      subsequent surgery or follow-up imaging. MR imaging-guided biopsy results were
      compared with final histopathologic or follow-up imaging findings. RESULTS: At MR
      imaging-guided core-needle biopsy, malignancy was identified in 52 (61%) lesions:
      35 invasive cancers and 17 ductal carcinoma in situ (DCIS) lesions. Four (24%) of
      the 17 DCIS lesions were upgraded to invasive cancer at excisional biopsy or
      mastectomy. A high-risk lesion (ie, atypical ductal hyperplasia, atypical lobular
      hyperplasia, lobular carcinoma in situ, or radial scar) was identified in 18
      (21%) cases. Two (25%) of eight atypical ductal hyperplasia lesions were upgraded
      to DCIS at excision. No malignancy was found in the atypical lobular hyperplasia
      (n = 2), lobular carcinoma in situ (n = 5), or radial scar (n = 3) lesions.
      Fifteen (18%) lesions were found to be benign lesions of unknown type at excision
      or mastectomy. For 13 of these 15 lesions, the benign results were concordant
      with the imaging findings. Both (two of 86, 2%) discordant cases represented
      false-negative lesions. The remaining 13 benign lesions were validated at
      excisional biopsy (n = 9) or follow-up imaging (n = 4). CONCLUSION: Initial
      experience revealed MR imaging-guided 9-gauge vacuum-assisted core-needle breast
      biopsy to be a reasonable alternative to MR imaging-guided wire localization of
      suspicious lesions identified at MR imaging only, on the basis of published
      information regarding the latter.

PMID- 16304094
TI  - Automatic exposure control in CT: are we done yet?

PMID- 16304095
TI  - Responsible conduct of radiology research. Part V. The Health Insurance
      Portability and Accountability Act and research.
AB  - For the past 5 years, the regulatory environment for research involving humans
      has been turbulent, with criticism coming from the federal government, the
      academic community, and the press. The purpose of this series of articles is to
      explain the ethical and legal bases for responsible conduct of radiology research
      and the rules that an investigator must follow. The purpose of this fifth part of
      the series is to explain the requirements of the Privacy Rule, which is a
      component of the Health Insurance Portability and Accountability Act (HIPAA), as
      they relate to human research. Under the HIPAA Privacy Rule, researchers within
      covered entities must follow appropriate methods as they use or disclose
      protected health information (PHI). Investigators should know the conditions
      under which PHI may be accessed for research purposes (ie, with authorization or
      waiver of authorization, when only a limited data set is evaluated, if data have
      been de-identified, or in reviews preparatory to research). Furthermore,
      researchers should know which information, such as the Notice of Privacy
      Practices and the Accounting of Disclosures, must be provided to potential
      subjects, when appropriate. At the conclusion of this article, several scenarios
      related to various types of radiology research and related regulatory
      requirements are presented.

PMID- 16304100
TI  - Factors associated with academic radiology research productivity.
AB  - PURPOSE: To determine factors associated with research productivity among all
      university radiology departments in the United States. MATERIALS AND METHODS: As
      an observational study, this was exempt from institutional review board approval.
      All 47,299 radiology articles from 1996 through 2003 that were indexed in the
      National Library of Medicine MEDLINE database were studied. Each article was
      assigned a "publication impact" score based on the impact factor of its source
      journal. These citations were then matched, along with National Institutes of
      Health (NIH) extramural grant, residency, fellowship, faculty, and geographic
      data, to 109 individual medical school radiology departments. Raw citation count
      was used to measure research quantity, and aggregate publication impact was used
      to measure quality. Regression analyses were used to compare the relationship
      between the study variables and research quality and quantity measures on the
      departmental and individual faculty level. RESULTS: Finalized statistical models
      accounted for 75%-88% of variance in productivity. NIH funding had a significant
      and positive association with all measures of research productivity (P < .001),
      with one article associated with 167,980 dollars in funding and one publication
      impact unit associated with 83,271 dollars in funding. Large resident program
      sizes (P < .001) and the presence of fellows (P = .007) also had a significant
      association. Geographic region, salary, and faculty characteristics had no
      detectable association. Extrapolations based on these results estimated the cost
      of annual global radiology research at 907 million dollars, with the U.S.
      component at at least 417 million dollars. NIH funding accounted for 45% of the
      U.S. component. CONCLUSION: NIH funding, resident program size, and fellow
      characteristics are significantly associated with academic research output.

PMID- 16304101
TI  - Reproducibility of functional MR imaging: preliminary results of prospective
      multi-institutional study performed by Biomedical Informatics Research Network.
AB  - PURPOSE: To prospectively investigate the factors--including subject, brain
      hemisphere, study site, field strength, imaging unit vendor, imaging run, and
      examination visit--affecting the reproducibility of functional magnetic resonance
      (MR) imaging activations based on a repeated sensory-motor (SM) task. MATERIALS
      AND METHODS: The institutional review boards of all participating sites approved
      this HIPAA-compliant study. All subjects gave informed consent. Functional MR
      imaging data were repeatedly acquired from five healthy men aged 20-29 years who
      performed the same SM task at 10 sites. Five 1.5-T MR imaging units, four 3.0-T
      units, and one 4.0-T unit were used. The subjects performed bilateral finger
      tapping on button boxes with a 3-Hz audio cue and a reversing checkerboard. In a
      block design, 15-second epochs of alternating baseline and tasks yielded 85
      acquisitions per run. Functional MR images were acquired with block-design echo
      planar or spiral gradient-echo sequences. Brain activation maps standardized in a
      unit-sphere for the left and right hemispheres of each subject were constructed.
      Areas under the receiver operating characteristic curve, intraclass correlation
      coefficients, multiple regression analysis, and paired Student t tests were used
      for statistical analyses. RESULTS: Significant factors were subject (P < .005), k
      space (P < .005), and field strength (P = .02) for sensitivity and subject (P =
      .03) and k-space (P = .05) for specificity. At 1.5-T MR imaging, mean
      sensitivities ranged from 7% to 32% and mean specificities were higher than 99%.
      At 3.0 T, mean sensitivities and specificities ranged from 42% to 85% and from
      96% to 99%, respectively. At 4.0 T, mean sensitivities and specificities ranged
      from 41% to 73% and from 95% to 99%, respectively. Mean areas under the receiver
      operating characteristic curve (+/- their standard errors) were 0.77 +/- 0.05 at
      1.5 T, 0.90 +/- 0.09 at 3.0 T, and 0.95 +/- 0.02 at 4.0 T, with significant
      differences between the 1.5- and 3.0-T examinations and between the 1.5- and 4.0
      T examinations (P < .01 for both comparisons). Intraclass correlation
      coefficients ranged from 0.49 to 0.71. CONCLUSION: MR imaging at 3.0- and 4.0-T
      yielded higher reproducibility across sites and significantly better results than
      1.5-T imaging. The effects of subject, k-space, and field strength on examination
      reproducibility were significant.

PMID- 16304102
TI  - Reinventing radiology in the digital age. Part III. Facilities, work processes,
      and job responsibilities.

PMID- 16304103
TI  - Management of thyroid nodules detected at US: Society of Radiologists in
      Ultrasound consensus conference statement.
AB  - The Society of Radiologists in Ultrasound convened a panel of specialists from a
      variety of medical disciplines to come to a consensus on the management of
      thyroid nodules identified with thyroid ultrasonography (US), with particular
      focus on which nodules should be subjected to US-guided fine needle aspiration
      and which thyroid nodules need not be subjected to fine-needle aspiration. The
      panel met in Washington, DC, October 26-27, 2004, and created this consensus
      statement. The recommendations in this consensus statement, which are based on
      analysis of the current literature and common practice strategies, are thought to
      represent a reasonable approach to thyroid nodular disease.

PMID- 16304104
TI  - Education and the art of uncertainty.

PMID- 16304105
TI  - Robustness of computerized lesion detection and classification scheme across
      different breast US platforms.
AB  - PURPOSE: To evaluate the performance of a computerized detection and diagnosis
      method with breast ultrasonographic (US) images obtained with US equipment from
      two different manufacturers. MATERIALS AND METHODS: Two independent clinical
      breast US databases were used in this performance study. Data collection and
      database use were HIPAA-compliant and followed institutional review board
      approved protocols, with waiver of informed consent. One database consisted of
      1740 images obtained in 458 women with Philips US equipment. The other database
      consisted of 151 images obtained in 151 women with Siemens US equipment. The
      testing protocols included independent testing and round-robin analysis. The
      computerized scheme detects potential lesions, calculates imaging features for
      all candidate lesions, and subsequently classifies candidate lesions into
      different categories. Two separate classification tasks were evaluated:
      distinction between all actual lesions and false-positive detections and
      distinction between actual cancers and all other detected lesion candidates.
      Statistical analysis was performed by using both receiver operating
      characteristic (ROC) and free-response ROC methods. RESULTS: For the distinction
      between all actual lesions and false-positive detections, area under the ROC
      curve (A(z)) values ranged between 0.87 and 0.95 for different testing protocols.
      In two instances, the difference in performance between databases was significant
      (P < .01), but it was shown that this was due to the difference in size of the
      databases. In the distinction of cancer from all other detections, the A(z)
      values ranged between 0.80 and 0.86. No statistically significant difference was
      found among the different testing protocols in this instance. CONCLUSION: These
      results indicate that the performance of this fully automated computerized lesion
      detection and classification method, which demonstrated robustness over the
      different US equipment used, is promising.

PMID- 16304106
TI  - Differentiation of benign from malignant solid breast masses: conventional US
      versus spatial compound imaging.
AB  - PURPOSE: To compare prospectively the diagnostic performance of radiologists who
      used conventional ultrasonography (US) with that of radiologists who used spatial
      compound imaging for the differentiation of benign from malignant solid breast
      masses. MATERIALS AND METHODS: The study was approved by the institutional review
      board, and informed consent was obtained. Before excisional or needle biopsy was
      performed, conventional US and spatial compound images were obtained in 67
      patients (age range, 25-67 years; mean age, 45 years) with 75 solid breast masses
      (21 cancers and 54 benign lesions). Three experienced radiologists who did not
      perform the examinations independently analyzed US findings and indicated the
      probability of malignancy. Results were evaluated with kappa statistics and
      receiver operating characteristic (ROC) analysis. RESULTS: For US findings, the
      presence of calcifications was the most discordant feature (kappa = 0.372)
      between conventional US and spatial compound imaging, followed by echotexture
      (kappa = 0.439), boundary echo (kappa = 0.496), orientation (kappa = 0.518),
      echogenicity (kappa = 0.523), shape (kappa = 0.526), margin (kappa = 0.569), and
      posterior acoustic transmission (kappa = 0.669). The area under the ROC curve for
      conventional US was 0.79 for reader 1, 0.88 for reader 2, and 0.82 for reader 3,
      and the area under the ROC curve for spatial compound imaging was 0.85 for reader
      1, 0.88 for reader 2, and 0.89 for reader 3. The partial area index for
      conventional US was 0.29 for reader 1, 0.69 for reader 2, and 0.39 for reader 3,
      and the partial area index for spatial compound imaging was 0.29 for reader 1,
      0.65 for reader 2, and 0.39 for reader 3. The difference between the diagnostic
      performances of the two techniques was not significant (P > .05). CONCLUSION: The
      performance of the radiologists with respect to the characterization of solid
      breast masses was not significantly improved with spatial compound imaging.

PMID- 16304107
TI  - Phase-sensitive inversion-recovery MR imaging in the detection of myocardial
      infarction.
AB  - PURPOSE: To prospectively determine if phase-sensitive inversion-recovery (IR)
      magnetic resonance (MR) imaging eliminates the need to find the precise inversion
      time (TI) to null the signal of normal myocardium to achieve high contrast
      between infarcted and normal myocardium. MATERIALS AND METHODS: Informed consent
      was obtained from each patient for this prospective MR imaging research study,
      which was approved by the institutional review board. Twenty patients (16 men;
      four women; mean age, 56 years +/- 12.3) who experienced Q-wave myocardial
      infarction 2 weeks earlier were examined with a 1.5-T MR system 10 minutes after
      administration of 0.1 mmol per kilogram of body weight gadobenate dimeglumine. To
      determine the optimal TI, a TI scout sequence was used. A segmented two
      dimensional IR turbo fast low-angle shot (FLASH) sequence and a segmented two
      dimensional IR true fast imaging with steady-state precession (FISP) sequence
      that produces both phase-sensitive and magnitude-reconstructed images were used
      at TI values of 200-600 msec (TI values were varied in 100-msec steps) and at
      optimal TI (mean value, 330 msec). Contrast-to-noise ratios (CNRs) of normal and
      infarcted myocardium and the area of infarcted myocardium were determined.
      Magnitude-reconstructed IR turbo FLASH images were compared with magnitude
      reconstructed and phase-sensitive IR true FISP images. Two-tailed unpaired sample
      Student t test was used to compare CNRs, and two-tailed paired-sample Student t
      test was used to compare area of infarction. RESULTS: Mean CNR of images acquired
      with IR turbo FLASH and IR true FISP (phase-sensitive and magnitude-reconstructed
      images) at optimal TI (mean value, 330 msec) were 6.6, 6.2, and 6.1,
      respectively. For a TI of 200 msec, CNR values were -4.3, -4.0, and 7.2,
      respectively; for TI of 600 msec, CNR values were 3.1, 3.3, and 4.3,
      respectively. Area of infarcted myocardium was underestimated on magnitude
      reconstruction images (P = .002-.03) for short TI values (ie, 200 msec) for both
      sequences and for a TI of 300 msec for IR true FISP but not on phase-sensitive
      reconstructed IR true FISP images when compared with IR turbo FLASH images
      obtained at optimal TI. CONCLUSION: Phase-sensitive image reconstruction results
      in reduced need for precise choice of TI and more consistent image quality.

PMID- 16304108
TI  - Corrected tetralogy of Fallot: delayed enhancement in right ventricular outflow
      tract.
AB  - PURPOSE: To evaluate retrospectively the presence of fibrosis and largest
      diameter of the right ventricular outflow tract (RVOT) by using delayed
      enhancement magnetic resonance (MR) imaging in patients who had undergone initial
      correction for tetralogy of Fallot. MATERIALS AND METHODS: MR imaging was
      performed in 24 consecutive patients (16 male, eight female; mean age, 25 years;
      age range, 13-47 years) with corrected tetralogy of Fallot. The study protocol
      was approved by the local ethics committee, and informed consent was not
      required. Fifteen minutes after injection of 0.2 mmol/kg gadopentetate
      dimeglumine, an inversion-recovery turbo field-echo sequence was applied for
      detection of delayed enhancement. Right ventricular volumes, ejection fraction,
      and anterior-posterior diameter of the RVOT were calculated. Mann-Whitney
      nonparametric testing was used to compare measurements of ventricular volume,
      function, and anterior-posterior diameter of the RVOT in the presence or absence
      of delayed enhancement. Correlation was tested with Pearson coefficient. RESULTS:
      Delayed enhancement was seen in 17 patients in the RVOT. During initial surgery,
      transannular patching was performed in 13 (76%) of 17 patients, RVOT patching in
      one (6%) of 17 patients, and the Brock procedure in two (12%) of 17 patients. In
      one patient, the type of initial RVOT repair was unknown. Patients with delayed
      enhancement in the RVOT, as compared with those without delayed enhancement in
      the RVOT, had increased RVOT diameter (32 mm +/- 7 [standard deviation] vs 22 mm
      +/- 3, P < .01), decreased right ventricular ejection fraction (43% +/- 6.3 vs
      54% +/- 10, P < .001), and increased end-diastolic volume (175 mL/m2 +/- 42 vs
      118 mL/m2 +/- 34, P < .01). The diameter of the RVOT correlated with increased
      right ventricular end-systolic volume (R = 0.86) and was inversely related to
      ejection fraction (R = -0.65). CONCLUSION: Delayed enhancement occurs frequently
      in patients after correction for tetralogy of Fallot. Delayed enhancement in the
      RVOT was associated with RVOT dilatation, which adversely affects right
      ventricular hemodynamics.

PMID- 16304110
TI  - Case 89: Retroperitoneal extraskeletal osteosarcoma.

PMID- 16304111
TI  - CT colonography in the detection of colorectal polyps and cancer: systematic
      review, meta-analysis, and proposed minimum data set for study level reporting.
AB  - PURPOSE: To assess the methodologic quality of available data in published
      reports of computed tomographic (CT) colonography by performing systematic review
      and meta-analysis. MATERIALS AND METHODS: The MEDLINE database was searched for
      colonography reports published between 1994 and 2003, without language
      restriction. The terms colonography, colography, CT colonoscopy, CT pneumocolon,
      virtual colonoscopy, and virtual endoscopy were used. Studies were selected if
      the focus was detection of colorectal polyps verified with within-subject
      reference colonoscopy by using key methodologic criteria based on information
      presented at the Fourth International Symposium on Virtual Colonoscopy (Boston,
      Mass). Two reviewers independently abstracted methodologic characteristics. Per
      patient and per-polyp detection rates were extracted, and authors were contacted,
      when necessary. Per-patient sensitivity and specificity were calculated for
      different lesion size categories, and Forest plots were produced. Meta-analysis
      of paired sensitivity and specificity was conducted by using a hierarchical model
      that enabled estimation of summary receiver operating characteristic curves
      allowing for variation in diagnostic threshold, and the average operating point
      was calculated. Per-polyp sensitivity was also calculated. RESULTS: Of 1398
      studies considered for inclusion, 24 met our criteria. There were 4181 patients
      with a study prevalence of abnormality of 15%-72%. Meta-analysis of 2610
      patients, 206 of whom had large polyps, showed high per-patient average
      sensitivity (93%; 95% confidence interval [CI]: 73%, 98%) and specificity (97%;
      95% CI: 95%, 99%) for colonography; sensitivity and specificity decreased to 86%
      (95% CI: 75%, 93%) and 86% (95% CI: 76%, 93%), respectively, when the threshold
      was lowered to include medium polyps. When polyps of all sizes were included,
      studies were too heterogeneous in sensitivity (range, 45%-97%) and specificity
      (range, 26%-97%) to allow meaningful meta-analysis. Of 150 cancers, 144 were
      detected (sensitivity, 95.9%; 95% CI: 91.4%, 98.5%). Data reporting was
      frequently incomplete, with no generally accepted format. CONCLUSION: CT
      colonography seems sufficiently sensitive and specific in the detection of large
      and medium polyps; it is especially sensitive in the detection of symptomatic
      cancer. Studies are poorly reported, however, and the authors propose a minimum
      data set for study reporting.

PMID- 16304112
TI  - Fetal sheep brains: findings at functional blood oxygen level-dependent 3-T MR
      imaging--relationship to maternal oxygen saturation during hypoxia.
AB  - PURPOSE: To quantify the dependence of the signal intensity (SI) at blood oxygen
      level-dependent (BOLD) magnetic resonance (MR) imaging of fetal sheep brains on
      maternal oxygen saturation and to investigate the influence of positions of
      regions of interest (ROIs). MATERIALS AND METHODS: All experimental protocols
      were reviewed and approved by the local authorities on animal protection. The
      brains of singleton fetuses of five anesthetized sheep were subjected to rapid
      sequences (single-shot echo-planar imaging) of BOLD measurements with a 3-T MR
      imaging unit. Maternal oxygen saturation and heart rate were recorded
      continuously. After a normoxic phase, hypoxia was induced by reducing the oxygen
      in a ventilated gas mixture. ROIs were placed in the cerebrum at a reference
      level and in the cerebellum. Normalized BOLD SI values were calculated from the
      mean values of steady-state BOLD SIs at the control (SI(c)) and hypoxic (SI(h))
      plateaus as follows: normalized BOLD SI = (SI(h)/ SI(c)) x 100. Normalized BOLD
      SI values were correlated with maternal oxygen saturation, and linear regression
      (slope) analysis was performed. Additionally, ROIs were varied in section level
      and position. Differences in normalized BOLD SI values for ROI placements were
      calculated by using analysis of variance. A t test was performed to evaluate
      differences. RESULTS: Mean maternal oxygen saturation (as the percentage of
      oxygen in the blood) was 88% (95% confidence interval [CI]: 80%, 96%) in the
      control period. During hypoxia, it was reduced to 62% (95% CI: 50%, 75%), while
      fetal normalized BOLD SI decreased to 64% (95% CI: 44%, 85%) in the cerebrum and
      56% (95% CI: 32%, 80%) in the cerebellum. Correlations between normalized BOLD SI
      values and maternal oxygen saturation were as follows: r2 = 0.84 and slope = 1.27
      (95% CI: 1.17, 1.36) in the cerebrum and r2 = 0.83 and slope = 1.54 (95% CI:
      1.44, 1.63) in the cerebellum. Normalized BOLD SI was 4% lower in the section
      above the reference level. Variations in normalized BOLD SI for different ROI
      positions ranged between 0% and 12%. CONCLUSION: The depletion of oxygen supply
      is reflected by decreases in fetal brain BOLD SIs that are more distinct in the
      cerebellum than in the cerebrum. Normalized BOLD SI is influenced only slightly
      by ROI position.

PMID- 16304113
TI  - Colorectal polyps: detection with low-dose multi-detector row helical CT
      colonography versus two sequential colonoscopies.
AB  - PURPOSE: To prospectively evaluate the diagnostic accuracy of low-radiation-dose
      computed tomographic (CT) colonography for detection of colorectal polyps by
      using two sequential colonoscopies, with the second colonoscopy as the reference
      standard. MATERIALS AND METHODS: The study was local ethics committee approved,
      and all patients gave written informed consent. Colonographic images were
      acquired by using a low-dose multi-detector row CT protocol (effective
      milliampere-second setting, 10 mAs). Three observers interpreted the CT
      colonographic data separately and independently by using a two-dimensional
      technique. Initial conventional colonoscopy was performed by an endoscopist
      unaware of the CT colonographic findings. Second colonoscopy performed within 2
      weeks by a colonoscopist aware of both the CT colonographic and the initial
      colonoscopic findings served as the reference standard. The sensitivities of CT
      colonography and initial colonoscopy were calculated on a per-polyp and a per
      patient basis. Specificities and positive and negative predictive values also
      were calculated on a per-patient basis. RESULTS: Eighty-eight patients underwent
      CT colonography and initial conventional colonoscopy on the same day. Per-polyp
      sensitivities were 62% and 83% for CT colonography and initial colonoscopy,
      respectively. Sensitivities for detection of polyps 6 mm in diameter or larger
      were 86% and 84% for CT colonography and initial colonoscopy, respectively.
      Initial colonoscopy failed to depict 16 polyps, six of which were correctly
      detected with CT colonography. For identification of patients with polyps 6 mm in
      diameter or larger, CT colonography and initial colonoscopy, respectively, had
      sensitivities of 84% and 90%, specificities of 82% and 100%, positive predictive
      values of 70% and 100%, and negative predictive values of 91% and 95%.
      CONCLUSION: Low-dose CT colonography compares favorably with colonoscopy for
      detection of colorectal polyps 6 mm in diameter or larger, with markedly
      decreased performance for detection of polyps 5 mm in diameter or smaller.

PMID- 16304114
TI  - Lymphatic drainage from esophagogastric tract: feasibility of endoscopic CT
      lymphography for direct visualization of pathways.
AB  - PURPOSE: To evaluate the feasibility of an endoscopic computed tomographic (CT)
      lymphography technique with submucosal injection of iopamidol for direct
      visualization of lymphatic drainage pathways in dogs and in patients with
      operable esophageal cancer. MATERIALS AND METHODS: With institutional animal
      committee approval, a total of 2 mL of undiluted iopamidol was injected into the
      esophageal (n = 6) or gastric (n = 3) submucosa in nine dogs by using a flexible
      endoscope. Multi-detector row CT images (section thickness, 1.25 mm) were
      obtained before contrast material injection and during the 10 minutes after
      injection. The animals were euthanized so that their lymphatic anatomy could be
      examined. With ethical committee approval and patient informed consent, nine
      patients with esophageal cancer also underwent CT lymphography with peritumoral
      injection of 2 mL of iopamidol, followed by esophagectomy and regional lymph node
      dissection with CT lymphographic guidance. The histopathologic features of
      dissected nodes, including sentinel lymph nodes (SLNs), were examined. RESULTS:
      CT lymphography depicted the direct connection of lymphatic drainage vessels with
      enhanced and/or unenhanced nodes (ie, SLNs) as early as within 5 minutes after
      contrast material injection in all subjects. All 13 SLNs in dogs (1.4 nodes per
      animal) and 18 SLNs in patients (two nodes per patient) were found and dissected
      at the correct location by using CT lymphographic guidance. In patients,
      histopathologic examination revealed the high predictive value of CT
      lymphographic-guided SLN biopsy: Only one of the preoperatively identified SLNs
      in three patients and both SLNs and adjacent nodes in two patients were positive
      for metastasis; all resected nodes in the remaining four patients were negative.
      CONCLUSION: Endoscopic CT lymphography is a feasible method for visualizing the
      direct connection between and the accurate anatomic location of SLNs and
      lymphatic drainage vessels.

PMID- 16304115
TI  - Assessment of 100 live potential renal donors for laparoscopic nephrectomy with
      multi-detector row helical CT.
AB  - PURPOSE: To retrospectively review the authors' experience with multi-detector
      row helical computed tomography (CT) in assessing 100 consecutive live potential
      renal donors. MATERIALS AND METHODS: Hospital ethical committee approval was
      obtained; informed patient consent was not required. One hundred potential renal
      donors underwent multi-detector row CT assessment. Nonenhanced, arterial phase,
      and nephrographic phase examinations were performed. Delayed topograms were
      acquired to visualize the collecting system anatomy. A vascular radiologist
      prospectively interpreted the multi-detector row CT images. A second vascular
      radiologist, blinded to the initial results, retrospectively reviewed the images.
      Eighty candidates subsequently underwent donor nephrectomy, including 70
      laparoscopic donor nephrectomies (LDNs) and 10 open donor nephrectomies (ODNs).
      Surgical findings served as the reference standard for 80 kidneys. The imaging
      findings in all 100 candidates (200 kidneys) were reviewed, although these
      findings were considered observational data only because there was no reference
      standard for 120 kidneys. RESULTS: Multi-detector row CT findings predicted
      uncomplicated LDN in 67 of 70 patients. Small upper-pole capsular arteries
      arising from the distal main renal artery in two patients were not described in
      the multi-detector row CT report: In one patient, the arising vessels resulted in
      conversion to ODN because of bleeding; in the other patient, arterial
      reconstruction was performed. In another patient, conversion to ODN was necessary
      because of ongoing bleeding from an avulsed large lumbar venous tributary to the
      left renal vein. Observational data revealed that multiple renal arteries--most
      of which were accessory renal arteries--were seen in 52 (26%) kidneys. Early
      branching of the main renal artery was seen in 24 (12%) kidneys, and main renal
      arterial abnormalities were identified in six (3%). Capsular arteries were
      detected in 10 (5%) kidneys. Major variations in the anatomy of the main renal
      veins--including multiple right renal veins, a retroaortic left renal vein, and a
      circumaortic left renal vein--were seen in 28 (14%) kidneys. Large (>5 mm in
      diameter) systemic tributaries to the left renal vein were seen in 25 (25%)
      kidneys. There was no significant interobserver disagreement between the vascular
      radiologists. CONCLUSION: Multi-detector row CT findings can predict successful
      LDN in live potential renal donors.

PMID- 16304116
TI  - Interosseous ligament tears of the wrist: comparison of multi-detector row CT
      arthrography and MR imaging.
AB  - PURPOSE: To compare the accuracy of multi-detector row computed tomographic (CT)
      arthrography and magnetic resonance (MR) imaging in depicting tears of dorsal,
      central, and palmar segments of scapholunate (SL) and lunotriquetral (LT)
      ligaments in cadavers. MATERIALS AND METHODS: Cadaver wrists were obtained and
      used according to institutional guidelines and with informed consent of donors
      prior to death. Nine cadaver wrists of eight subjects were evaluated. MR images
      were obtained with a 1.5-T MR unit. Imaging protocol included intermediate
      weighted coronal and transverse fast spin-echo and coronal three-dimensional
      gradient-echo sequences. Multi-detector row CT arthrography was performed after
      tricompartmental injection of 3-6 mL of contrast material with a concentration of
      160 mg per milliliter of iodine. Palmar, dorsal, and central segments of both
      ligaments were analyzed on transverse and coronal MR images and multiplanar multi
      detector row CT reconstructions by two musculoskeletal radiologists working
      independently. Open inspection of the wrists was the reference standard.
      Sensitivity, specificity, accuracy, and positive and negative predictive values
      were calculated from the imaging and gross pathologic readings. Statistical
      significance was calculated with the McNemar test. Weighted kappa values for
      interobserver agreement were calculated for both imaging modalities. RESULTS: All
      ligament segments could be visualized in all cases with both imaging modalities.
      CT arthrography was more sensitive (100%) than MR imaging (60%) in detection of
      palmar segment tears (P = .62); specificity of both imaging modalities was 77%.
      Sensitivity (CT arthrography, 86%; MR imaging, 79%) and specificity (CT
      arthrography, 50%; MR imaging, 25%) for detection of the central segment tears
      were determined. Dorsal segment tears were detected only with CT arthrography,
      while all tears were missed with MR imaging (P = .02). Interobserver agreement
      was better for multi-detector row CT arthrography (kappa = 0.37-0.78) than for MR
      imaging (kappa = -0.33 to -0.10). CONCLUSION: Performance in depiction of palmar
      and central segment tears of SL and LT ligaments is almost equal for multi
      detector row CT arthrography and MR imaging, with much higher interobserver
      reliability for CT arthrography. CT arthrography is significantly superior to MR
      imaging in the detection of dorsal segment tears of SL and LT ligaments.

PMID- 16304117
TI  - Direct comparison of FDG PET and CT findings in patients with lymphoma: initial
      experience.
AB  - PURPOSE: To retrospectively compare fluorine 18 fluorodeoxyglucose (FDG) positron
      emission tomographic (PET) and computed tomographic (CT) findings at the same
      anatomic locations in patients with lymphoma by using a combined PET/CT scanner
      and to analyze the lesions on metabolic and anatomic bases to evaluate causes of
      discrepant findings between the two modalities. MATERIALS AND METHODS: The
      institutional review board allowed an exempt retrospective review of cancer PET
      database, and informed consent was waived. The study was HIPAA compliant. Fifty
      three patients with lymphoma (20 Hodgkin and 33 non-Hodgkin; mean age, 43 years;
      range, 12-83 years) who underwent FDG PET/CT were included. The PET and CT images
      were interpreted by two nuclear medicine physicians and one radiologist,
      respectively, blinded to the other imaging findings. Concordant PET and CT
      findings were regarded as positive or negative for lymphoma. The site with
      discordant findings was defined as positive for disease if it was accompanied by
      other PET- and CT-positive sites in the same patient or was confirmed clinically
      (histologic examination or progressive disease). Staging results were also
      compared by one nuclear medicine physician. RESULTS: Of a total of 1537 anatomic
      sites in 53 patients, 48 had discordant findings between PET and CT. Forty (83%)
      of the 48 sites had correct PET findings (31 positive, nine negative), five had
      correct CT findings, and three were unresolved. The 31 PET-positive and CT
      negative sites accounted for 23% of all 134 true-positive PET sites. PET provided
      accurate staging in an incremental nine (17%, upstaging in four and downstaging
      in five) of 53 patients in whom CT staging was incorrect. CT provided correct
      upstaging in two patients. CONCLUSION: FDG PET/CT as a combined modality may
      contribute substantially to lesion characterization and staging in patients with
      lymphoma.

PMID- 16304118
TI  - The spoke wheel sign: bowel.

PMID- 16304119
TI  - Bolus versus continuous infusion of microbubble contrast agent for liver US:
      initial experience.
AB  - Institutional review board approval and informed consent were obtained. To
      prospectively assess if continuous infusion of galactose-palmitic acid can
      prolong the duration of hepatic enhancement at ultrasonography over bolus
      injection, 11 patients received two injections--one bolus injection (2 mL/sec)
      and one continuous infusion (1.5 mL/min)--with the same dose of galactose
      palmitic acid (4 g, 300 mg/dL). Two unenhanced baseline sweep scans (mechanical
      index of 0.7 and 1.3) of the relevant liver lobe were acquired followed by
      contrast-enhanced sweeps after bolus injection and continuous infusion. Each
      sweep was saved as cine loops and analyzed with a personal computer. Duration of
      enhancement more than 3 dB was prolonged by continuous infusion from 4.3 minutes
      +/- 2.4 (+/-standard deviation) at bolus injection to 10.1 minutes +/- 3.0 (P <
      .005). Maximal parenchymal enhancement was 11.0 dB +/- 3.2 (bolus injection) and
      9.2 dB +/- 3.8 (infusion, P < .05). Peak liver-to-lesion contrast was 14.2 dB +/-
      6.3 (bolus injection) and 13.2 dB +/- 7.1 (infusion, not significant). Continuous
      infusion of galactose-palmitic acid markedly prolongs but slightly diminishes
      hepatic enhancement; liver-to-lesion contrast remains unchanged.

PMID- 16304121
TI  - Image-guided percutaneous radiofrequency ablation and incidence of post
      radiofrequency ablation syndrome: prospective survey.
AB  - PURPOSE: To evaluate prospectively the incidence of post-radiofrequency (RF)
      ablation syndrome and determine its impact on the quality of life in the 10 days
      after percutaneous RF ablation. MATERIALS AND METHODS: This study was approved by
      the institutional review board and was HIPAA compliant. Informed consent was
      obtained for this survey in all patients by the interventional nurse
      coordinators. Thirty-six patients (20 men, 16 women; mean age, 69.3 years; range,
      40-88 years) underwent RF ablation for 26 liver tumors and 17 renal tumors.
      Twenty control patients (11 men, nine women; mean age, 60.8 years; range, 35-76
      years) underwent biopsy of focal liver lesions or renal lesions. With a
      standardized questionnaire, a telephone survey was conducted on days 1, 3, 5, and
      10 after RF ablation or biopsy. The symptoms and interference with lifestyle were
      documented prospectively with a numeric intensity scale by using grades 0-10.
      Statistical analysis with Fisher exact test and analysis of variance was
      performed. RESULTS: After RF ablation, 15 (42%) patients developed low-grade
      fever (P < .001), 29 (81%) had flulike symptoms (P < .001), and four were
      asymptomatic. Symptoms peaked on day 3 and mainly resolved by day 10. Twelve
      (33%) patients had complete post-RF ablation syndrome: fever and flulike symptoms
      (P = .005). Flulike symptoms were more prolonged when they were accompanied with
      fever, peaked on day 5, and resolved more quickly for patients with renal lesions
      than they did for patients with liver lesions. Four patients had persistent fever
      caused by pneumonia (n = 2), pleural effusion and atelectasis (n = 1), or liver
      abscess (n = 1). No control patients developed both fever and flulike symptoms.
      Post-RF ablation patients with symptoms experienced significantly greater pain
      and interference with general and work activities, which peaked on day 1, than
      did control patients (P = .01 [pain], P < .001 [general and work activities]).
      CONCLUSION: Complete post-RF ablation syndrome occurs in approximately one-third
      of patients but is self-limiting within 10 days after the procedure. Persistent
      or late-onset fever may indicate concurrent infection elsewhere or possible
      abscess formation. SUPPLEMENTAL MATERIAL:
      radiology.rsnajnls.org/cgi/content/full/237/3/1097/DC1

PMID- 16304120
TI  - Radiographic-clinical correlation in severe acute respiratory syndrome: study of
      1373 patients in Hong Kong.
AB  - PURPOSE: To retrospectively analyze serial chest radiographs in all patients with
      severe acute respiratory syndrome (SARS) in Hong Kong for temporal changes and
      differences between patients who died and those who were discharged from the
      hospital and to compare radiographic and clinical parameters. MATERIALS AND
      METHODS: This retrospective study had ethics review board endorsement, and the
      need for informed consent was waived. Selected serial chest radiographs obtained
      from the time of presentation until discharge or death in 1373 patients with
      laboratory-confirmed SARS were scored. Scoring was based on the area and location
      of lung opacification on radiographs obtained at each of five milestones
      (presentation, beginning of ribavirin therapy, beginning of corticosteroid
      therapy, time of most severe radiographic appearance of disease, and before
      discharge or death). Extents of lung opacification at these five milestones were
      compared between patients who died and those who survived (by using a repeated
      measures analysis of variance model), and the temporal trend of the radiographic
      clinical parameters was analyzed (by using Cochran-Armitage trend testing,
      Kendall tau correlation coefficients, and descriptive graphic analysis). RESULTS:
      The final cohort consisted of 1373 patients (1212 of whom [485 male and 727
      female patients; mean age, 38.4 years] survived and 161 of whom [84 male and 77
      female patients; mean age, 63.0 years] died). Among survivors, older patients had
      more extensive radiographic changes than younger ones. However, among patients
      who died, older patients had less extensive radiographic opacification at the
      worst stage of disease and just before death than did younger patients. Despite a
      higher mortality risk for male patients, both sexes in the same outcome group had
      similar radiographic findings. For both outcome groups, the rate of radiographic
      progression was similar for the first 11 days but diverged afterwards. The extent
      of opacification increased by approximately one zone every 4-5 days for the
      initial 11 days. Radiographic scores correlated with the ratio of PaO2 to the
      fraction of inspired oxygen, lymphocyte count, lactate dehydrogenase level, and
      neutrophil count at each milestone and in terms of changes between milestones (P
      < .01 for all correlation coefficients, except for radiographic score and
      neutrophil count between the first two milestones). CONCLUSION: The initial
      extent of radiographic opacification may be useful for prognostic prediction.
      Radiographic progression correlates well with that of important clinical and
      laboratory parameters and may be used as an objective prognostic indicator early
      in SARS.

PMID- 16304122
TI  - Adjunctive abciximab improves patency and functional outcome in endovascular
      treatment of femoropopliteal occlusions: initial experience.
AB  - PURPOSE: To prospectively evaluate the safety and effectiveness of adjunctive
      administration of abciximab observed within 30 days and at 6 months after
      randomization in patients undergoing endovascular revascularization of long
      segment femoropopliteal occlusions. MATERIALS AND METHODS: The study was approved
      by the local ethical committee, and patients gave written informed consent. In a
      prospective, double-blind, placebo-controlled design, patients undergoing
      percutaneous treatment for long-segment (>5 cm) femoropopliteal occlusions were
      randomly assigned to receive abciximab or a placebo; all patients also received
      standard-dose heparin. Effectiveness and safety analyses were based on an
      intention-to-treat approach. Patency was calculated according to life-table
      analysis, and P values were derived from the log-rank statistic. The P values for
      dichotomous safety end points were calculated with the Fisher exact test. Odds
      ratios were calculated for subgroup analyses. Logistic regression modeling was
      used for analysis of the safety bleeding data. RESULTS: A total of 98 patients
      (103 limbs) were included: 47 patients received abciximab and 51 received a
      placebo. Patency with abciximab versus placebo was 95.7% versus 80.4% (relative
      risk, 0.21; 95% confidence interval: 0.05, 0.96; P = .02) at 30 days and was
      61.7% versus 41.2% (relative risk, 0.57; 95% confidence interval: 0.32, 1.01; P =
      .03), coupled with a better clinical outcome according to the Rutherford score,
      at the end of follow-up (P = .03). Risk of major bleeding was not significantly
      increased, while access-site bleeding was significantly higher among patients
      receiving abciximab (odds ratio, 2.9; 95% confidence interval: 1.04, 8.2; P =
      .04). CONCLUSION: The data show that adjunctive administration of abciximab has a
      favorable effect on patency and clinical outcome in patients undergoing complex
      femoropopliteal catheter interventions not hampered by serious bleeding.
      Treatment effect of abciximab observed at 30 days was maintained at 6-month
      follow-up.

PMID- 16304123
TI  - Kyphoplasty versus vertebroplasty to increase vertebral body height: a cadaveric
      study.
AB  - PURPOSE: To prospectively compare the vertebral height restoration achieved with
      kyphoplasty and vertebroplasty in fresh cadavers by using multi-detector row
      computed tomography (CT). MATERIALS AND METHODS: Institutional review board
      approval was not required because the donors had registered in and consented to
      an anatomic gift program prior to their death. Thirty-seven vertebrae were
      harvested from four donated cadavers of elderly female individuals (mean age, 82
      years; age range at death, 73-87 years). The vertebrae were dissected free of the
      surrounding muscles and imaged with multi-detector row CT. Compression fractures
      were induced, and the vertebrae were again imaged. The vertebrae were randomized
      to be treated with kyphoplasty (n = 19) or vertebroplasty (n = 18) and were then
      imaged at multi-detector row CT. The anterior, central, and posterior vertebral
      body heights and wedge angles were measured in the midsagittal plane of the
      reformatted images. The amount of cement injected was determined by weighing the
      vertebrae before and after treatment. The statistical significance of changes in
      vertebral body height, wedge angle, and weight with the two treatment techniques
      was evaluated with the independent t test or Mann-Whitney U test. RESULTS: The
      increase in vertebral height was greater with kyphoplasty than with
      vertebroplasty (5.1 mm vs 2.3 mm, respectively; P < .05). The original vertebral
      height was restored in 93% of vertebrae with kyphoplasty and in 82% with
      vertebroplasty (P < .05). There was a greater decrease in wedge angle with
      kyphoplasty than with vertebroplasty (3.1 degrees vs 1.6 degrees, respectively);
      however, this difference was not significant (P > .05). There was no significant
      difference in the amount of cement injected with kyphoplasty and vertebroplasty
      (P > .05). CONCLUSION: Kyphoplasty increased vertebral body height more than
      vertebroplasty in this model of acutely created fractures in fresh cadaver
      specimens.

PMID- 16304124
TI  - Failure to define the true problem: poor communication by radiologists.

PMID- 16304125
TI  - The "I" word in chest radiography... why is it such a dirty word?

PMID- 16304126
TI  - The term infiltrate can be used in reports, if....

PMID- 16304127
TI  - Infiltrate: a controversy without end.

PMID- 16304128
TI  - On using the term infiltrate in radiography reports.

PMID- 16304131
TI  - A community resilience approach to reducing ethnic and racial disparities in
      health.
AB  - Prevention Institute, a nonprofit, national center dedicated to health and well
      being, developed a toolkit for health and resilience in vulnerable environments
      (THRIVE), a community assessment tool, to help communities bolster factors that
      will improve health outcomes and reduce disparities experienced by racial and
      ethnic minorities. THRIVE is grounded in research and was developed with input
      from a national expert panel. It has demonstrated utility in urban, rural, and
      suburban settings. Within months of piloting, several communities had initiated
      farmer's markets and youth programs. THRIVE provides a framework for community
      members, coalitions, public health practitioners, and local decisionmakers to
      identify factors associated with poor health outcomes in communities of color;
      engage the range of partners needed to improve community health outcomes, such as
      planners, elected officials, businesses, housing, and transportation; and take
      action to remedy disparities.

PMID- 16304132
TI  - Distribution of education and population health: an ecological analysis of New
      York City neighborhoods.
AB  - OBJECTIVES: We assessed the relationship between distribution of education and
      health indicators in a large urban area to determine if distribution of education
      may be a determinant of population health. METHODS: We studied the association
      between distribution of education, measured with the education Gini coefficient,
      and rates of 8 health indicators in 59 neighborhoods in New York City. RESULTS:
      In separate adjusted ecological models, neighborhoods with more poorly
      distributed education had better population health indicators that might
      plausibly be associated with short-term changes in the social environment (e.g.,
      homicide and infant mortality rate); there was no association between education
      distribution and health indicators more likely to be associated with long-term
      accumulation of social and behavioral stressors (e.g., cardiovascular disease and
      chronic lung disease mortality rates). These findings were robust to measures of
      income and to adjustment for several potential confounders (e.g., gender and
      race/ethnicity). CONCLUSIONS: The presence in a neighborhood of highly educated
      people may be salutary for all residents, independent of the potentially
      deleterious consequences of income maldistribution.

PMID- 16304133
TI  - Mortality among very low-birthweight infants in hospitals serving minority
      populations.
AB  - OBJECTIVE: We investigated whether the proportion of Black very low-birth-weight
      (VLBW) infants treated by hospitals is associated with neonatal mortality for
      Black and White VLBW infants. METHODS: We analyzed medical records linked to
      secondary data sources for 74050 Black and White VLBW infants (501 g to 1500 g)
      treated by 332 hospitals participating in the Vermont Oxford Network from 1995 to
      2000. Hospitals where more than 35% of VLBW infants treated were Black were
      defined as "minority-serving." RESULTS: Compared with hospitals where less than
      15% of the VLBW infants were Black, minority-serving hospitals had significantly
      higher risk-adjusted neonatal mortality rates (White infants: odds ratio
      [OR]=1.30, 95% confidence interval [CI] = 1.09, 1.56; Black infants: OR = 1.29,
      95% CI = 1.01, 1.64; Pooled: OR = 1.28, 95% CI=1.10, 1.50). Higher neonatal
      mortality in minority-serving hospitals was not explained by either hospital or
      treatment variables. CONCLUSIONS: Minority-serving hospitals may provide lower
      quality of care to VLBW infants compared with other hospitals. Because VLBW Black
      infants are disproportionately treated by minority-serving hospitals, higher
      neonatal mortality rates at these hospitals may contribute to racial disparities
      in infant mortality in the United States.

PMID- 16304134
TI  - Stillbirths in the United States, 1981-2000: an age, period, and cohort analysis.
AB  - OBJECTIVES: We examined age, period, and cohort (APC) effects on temporal trends
      in stillbirths among Black and White women in the United States. METHODS: We
      conducted a cohort study of Black and White women who delivered a singleton live
      born or stillborn infant during 1981 through 2000. We analyzed stillbirth rates
      at 20 or more weeks of gestation within 7 age groups, 4 periods, and 10 "central"
      birth cohorts after adjusting for confounders. RESULTS: In both racial groups,
      women younger than 20 years or 35 years or older were at increased risk of
      stillbirth; risks decreased over successive periods in all age groups. Birth
      cohort had no impact on stillbirth trends among Blacks and only a small,
      nonsignificant effect among Whites. Analyses of various APC combinations showed
      that Blacks were at a 1.2- to 2.9-fold increased risk for stillbirth relative to
      Whites. Attributable fractions for stillbirth because of age, period, and cohort
      effects were 16.5%, 24.9%, and 0.1%, respectively, among Black women and 14.5%,
      36.2%, and 2.1%, respectively, among White women. CONCLUSIONS: Strong effects of
      age and period were observed in stillbirth trends, but these factors do not
      explain the persistent stillbirth disparity between Black and White women.

PMID- 16304135
TI  - Infant sleeping environment and asthma at 7 years: a prospective cohort study.
AB  - OBJECTIVES: We investigated the role of infant bedding items, as part of a
      composite bedding environment, in the development of childhood wheezing. METHODS:
      This prospective cohort investigation involved 863 children who participated in
      an infant survey in 1988 and an asthma study in Tasmania, Australia, in 1995. The
      derived 3 composite infant bedding categories corresponded to increasing numbers
      of house dust mite (HDM)-rich bedding items used. Outcomes measured included
      recent and frequent wheezing. RESULTS: Composite infant bedding used was
      associated with recent wheezing. Effects increased at increasing levels of HDM
      rich bedding items used. Effects were further enhanced by home environmental
      factors of bedroom heating, recent bedroom painting, and absence of bedroom
      carpeting. When any 2 or more of these environmental factors were present, a
      strong dose-response relationship was evident. CONCLUSIONS: Our results show that
      bedding exposures in infancy are prospectively associated with childhood wheezing
      and that home environmental conditions may modify this association.

PMID- 16304137
TI  - Do normal d-dimer levels reliably exclude cerebral sinus thrombosis? A solution
      of problems?

PMID- 16304136
TI  - Effects of physical activity on cognitive functioning in middle age: evidence
      from the Whitehall II prospective cohort study.
AB  - OBJECTIVES: We examined the association between physical activity and cognitive
      functioning in middle age. METHODS: Data were derived from a prospective
      occupational cohort study of 10308 civil servants aged 35-55 years at baseline
      (phase 1; 1985-1988). Physical activity level, categorized as low, medium, or
      high, was assessed at phases 1, 3 (1991-1994), and 5 (1997-1999). Cognitive
      functioning was tested at phase 5, when respondents were 46-68 years old.
      RESULTS: In both prospective (odds ratio [OR] = 1.65; 95% confidence interval
      [CI]=1.30, 2.10) and cross-sectional (OR=1.79; 95% CI=1.38, 2.32) analyses, low
      levels of physical activity were a risk factor for poor performance on a measure
      of fluid intelligence. Analyses aimed at assessing cumulative effects (summary of
      physical activity levels at the 3 time points) showed a graded linear
      relationship with fluid intelligence, with persistently low levels of physical
      activity being particularly harmful (OR=2.21; 95% CI=1.37, 3.57). CONCLUSIONS:
      Low levels of physical activity are a risk factor for cognitive functioning in
      middle age, fluid intelligence in particular.

PMID- 16304138
TI  - Magnesium for delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage:
      time for a paradigm shift?

PMID- 16304142
TI  - Prospects for aminoacyl-tRNA synthetase inhibitors as new antimicrobial agents.

PMID- 16304143
TI  - Biphenylsulfonacetic acid inhibitors of the human papillomavirus type 6 E1
      helicase inhibit ATP hydrolysis by an allosteric mechanism involving tyrosine
      486.
AB  - Human papillomaviruses (HPVs) are the causative agents of benign and malignant
      lesions of the epithelium. Despite their high prevalence, there is currently no
      antiviral drug for the treatment of HPV-induced lesions. The ATPase and helicase
      activities of the highly conserved E1 protein of HPV are essential for viral DNA
      replication and pathogenesis and hence are considered valid antiviral targets. We
      recently described novel biphenylsulfonacetic acid inhibitors of the ATPase
      activity of E1 from HPV type 6 (HPV6). Based on kinetics and mutagenesis studies,
      we now report that these compounds act by an allosteric mechanism. They are
      hyperbolic competitive inhibitors of the ATPase activity of HPV6 E1 and also
      inhibit its helicase activity. Compounds in this series can also inhibit the
      ATPase activity of the closely related enzyme from HPV11; however, the most
      potent inhibitors of HPV6 E1 are significantly less active against the type 11
      protein. We identified a single critical residue in HPV6 E1, Tyr-486, substituted
      by a cysteine in HPV11, which is primarily responsible for this difference in
      inhibitor potency. Interestingly, HPV18 E1, which also has a tyrosine at this
      position, could be inhibited by biphenylsulfonacetic acid derivatives, thereby
      raising the possibility that this class of inhibitors could be optimized as
      antiviral agents against multiple HPV types. These studies implicate Tyr-486 as a
      key residue for inhibitor binding and define an allosteric pocket on HPV E1 that
      can be exploited for future drug discovery efforts.

PMID- 16304144
TI  - Activities of acyclic nucleoside phosphonates against Orf virus in human and
      ovine cell monolayers and organotypic ovine raft cultures.
AB  - Orf virus, a member of the Parapoxvirus genus, causes a contagious pustular
      dermatitis in sheep, goats, and humans. Previous studies have demonstrated the
      activity of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC;
      cidofovir; Vistide) against orf virus in cell culture and humans. We have
      evaluated a broad range of acyclic nucleoside phosphonates (ANPs) against several
      orf virus strains in primary lamb keratinocytes (PLKs) and human embryonic lung
      (HEL) monolayers. HPMPC, (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-
      diaminopurine (HPMPDAP), and (R)-9-[3-hydroxy-2-(phosphonomethoxy)propoxy]-2,4
      diaminopyrimidine (HPMPO-DAPy) were three of the most active compounds that were
      subsequently tested in a virus yield assay with PLK and HEL cells by virus
      titration and DNA quantification. HPMPC, HPMPDAP, and HPMPO-DAPy were evaluated
      for their activities against orf virus replication in organotypic epithelial raft
      cultures from differentiated PLK cells. At the highest concentrations (50 and 20
      microg/ml), full protection was provided by the three drugs, while at 5
      microg/ml, only HPMPDAP and HPMPC offered partial protection. The activities of
      the three compounds in the raft culture system were confirmed by quantification
      of infectious virus and viral DNA. These findings provide a rationale for the use
      of HPMPC and other ANPs in the treatment of orf (contagious ecthyma) in humans
      and animals.

PMID- 16304145
TI  - Role of silver ions in destabilization of intermolecular adhesion forces measured
      by atomic force microscopy in Staphylococcus epidermidis biofilms.
AB  - In this paper, we report on the potential use of atomic force microscopy (AFM) as
      a tool to measure the intermolecular forces in biofilm structures and to study
      the effect of silver ions on sessile Staphylococcus epidermidis cell viability
      and stability. We propose a strategy of destabilizing the biofilm matrix by
      reducing the intermolecular forces within the extracellular polymeric substances
      (EPSs) using a low concentration (50 ppb) of silver ions. Our AFM studies on the
      intermolecular forces within the EPSs of S. epidermidis RP62A and S.epidermidis
      1457 biofilms suggest that the silver ions can destabilize the biofilm matrix by
      binding to electron donor groups of the biological molecules. This leads to
      reductions in the number of binding sites for hydrogen bonds and electrostatic
      and hydrophobic interactions and, hence, the destabilization of the biofilm
      structure.

PMID- 16304146
TI  - New reporter cell line to evaluate the sequential emergence of multiple human
      cytomegalovirus mutations during in vitro drug exposure.
AB  - We developed a new reporter cell line for human cytomegalovirus (HCMV) drug
      susceptibility testing. This cell line was obtained by incorporating the
      luciferase reporter gene under the control of an HCMV-specific promoter into the
      genome of astrocytoma cells (U373MG). We then used our reporter cell line to
      evaluate phenotypic changes conferred by the sequential emergence of HCMV UL54
      and UL97 mutations following long-term drug exposure. The laboratory strain AD169
      was passaged in the presence of increasing concentrations of ganciclovir (one
      viral line) or foscarnet (two viral lines). Resistant viruses were plaque
      purified at five different concentrations of ganciclovir and at three different
      concentrations of foscarnet. In addition to the previously described M460I and
      L595S UL97 mutations and the L545S and V812L UL54 mutations, exposition to
      ganciclovir (up to 3,000 microM) resulted in the selection of two unreported UL54
      mutations (P829S and D879G). Passages in the presence of foscarnet (up to 3,000
      microM) resulted in the selection of seven not previously described UL54
      mutations (K500N, T552N, S585A, N757K, L802V, L926V, and L957F) in addition to
      the N408D mutation that has been associated with ganciclovir and cidofovir
      resistance. Long-term exposure of HCMV to either ganciclovir or foscarnet
      ultimately resulted in the selection of multiple UL54 mutations that conferred
      high levels of resistance to all approved HCMV DNA polymerase inhibitors, i.e.,
      ganciclovir, cidofovir, and foscarnet. Emergence of each viral mutation conferred
      stepwise increases in drug 50% inhibitory concentrations that could be
      objectively measured with the new reporter cell assay.

PMID- 16304147
TI  - Comparative efficacies of conventional amphotericin b, liposomal amphotericin B
      (AmBisome), caspofungin, micafungin, and voriconazole alone and in combination
      against experimental murine central nervous system aspergillosis.
AB  - Central nervous system (CNS) aspergillosis is a severe disease that responds
      poorly to current therapies. The current studies examined the efficacies of
      several antifungal agents alone or in combination with a murine model of CNS
      aspergillosis. Immunosuppressed mice were infected intracerebrally with
      Aspergillus fumigatus and treated with an amphotericin B preparation, an
      echinocandin, or voriconazole (VCZ) given alone or in combination. Monotherapy
      studies showed that micafungin (MICA), caspofungin (CAS), VCZ, conventional
      amphotericin B (AMB), Abelcet (ABLC) (a lipid-carried AMB formulation; Enzon
      Pharmaceuticals, Inc.), and AmBisome (AmBi) (liposomal AMB; Gilead Sciences,
      Inc.) were efficacious. However, doses of AmBi above 15 mg/kg of body weight
      showed reduced efficacy. Neither MICA nor CAS showed dose responsiveness at the
      doses tested (1, 5, or 10 mg/kg). Only the 40-mg/kg dose of VCZ was effective.
      AmBi and ABLC showed dose responsiveness, with 10-mg/kg doses causing a
      significant reduction in fungal burden; they had equivalent activities at the 10
      mg/kg dose. Suboptimal dosages of AmBi in combination with MICA, CAS, or VCZ were
      effective in prolonging survival. However, significantly enhanced activity was
      demonstrated only with AmBi and VCZ in combination. AmBi in combination with MICA
      or CAS showed a trend toward enhanced activity, but the combination was not
      significantly superior to monotherapy. The use of AmBi with CAS or VCZ at optimal
      doses did not improve efficacy. Cure was not attained with any dosage
      combinations. These results indicate that AmBi in combination with VCZ may be
      superior for treatment of CNS aspergillosis; combinations of AmBi and MICA or CAS
      were not antagonistic and may have a slight benefit.

PMID- 16304148
TI  - Channel formation by CarO, the carbapenem resistance-associated outer membrane
      protein of Acinetobacter baumannii.
AB  - It has been recently shown that resistance to both imipenem and meropenem in
      multidrug-resistant clinical strains of Acinetobacter baumannii is associated
      with the loss of a heat-modifiable 25/29-kDa outer membrane protein, called CarO.
      This study aimed to investigate the channel-forming properties of CarO. Mass
      spectrometry analyses of this protein band detected another 25-kDa protein
      (called Omp25), together with CarO. Both proteins presented similar
      physicochemical parameters (M(w) and pI). We overproduced and purified the two
      polypeptides as His-tagged recombinant proteins. Circular dichroism analyses
      demonstrated that the secondary structure of these proteins was mainly a beta
      strand conformation with spectra typical of porins. We studied the channel
      forming properties of proteins by reconstitution into artificial lipid bilayers.
      In these conditions, CarO induced ion channels with a conductance value of 110 pS
      in 1 M KCl, whereas the Omp25 protein did not form any channels, despite its
      suggested porin function. The pores formed by CarO showed a slight cationic
      selectivity and no voltage closure. No specific imipenem binding site was found
      in CarO, and this protein would rather form unspecific monomeric channels.

PMID- 16304149
TI  - Inhibition of human immunodeficiency virus type 1 reverse transcriptase, RNase H,
      and integrase activities by hydroxytropolones.
AB  - Human immunodeficiency virus type I reverse transcriptase (RT) possesses distinct
      DNA polymerase and RNase H sites, whereas integrase (IN) uses the same active
      site to perform 3'-end processing and strand transfer of the proviral DNA. These
      four enzymatic activities are essential for viral replication and require metal
      ions. Two Mg2+ ions are present in the RT polymerase site, and one or two Mg2+
      ions are required for the catalytic activities of RNase H and IN. We tested the
      possibility of inhibition of the RT polymerase and RNase H as well as the IN 3'
      end processing and transfer activities of purified enzymes by a series of 3,7
      dihydroxytropolones designed to target two Mg2+ ions separated by approximately
      3.7 angstroms. The RT polymerase and IN 3' processing and strand transfer
      activities were inhibited at submicromolar concentrations, while the RNase H
      activity was inhibited in the low micromolar range. In all cases, the lack of
      inhibition by tropolones and O-methylated 3,7-dihydroxytropolones was consistent
      with the active molecules binding the metal ions in the active site. In addition,
      inhibition of the DNA polymerase activity was shown to depend on the Mg2+
      concentration. Furthermore, selective inhibitors were identified for several of
      the activities tested, leaving some potential for design of improved inhibitors.
      However, all tested compounds exhibited cellular toxicity that presently limits
      their applications.

PMID- 16304151
TI  - Interaction of ritonavir-boosted tipranavir with loperamide does not result in
      loperamide-associated neurologic side effects in healthy volunteers.
AB  - Loperamide (LOP) is a peripherally acting opioid receptor agonist used for the
      management of chronic diarrhea through the reduction of gut motility. The lack of
      central opioid effects is partly due to the efflux activity of the multidrug
      resistance transporter P-glycoprotein (P-gp) at the blood-brain barrier. The
      protease inhibitors are substrates for P-gp and have the potential to cause
      increased LOP levels in the brain. Because protease inhibitors, including
      tipranavir (TPV), are often associated with diarrhea, they are commonly used in
      combination with LOP. The level of respiratory depression, the level of pupil
      constriction, the pharmacokinetics, and the safety of LOP alone compared with
      those of LOP-ritonavir (RTV), LOP-TPV, and LOP-TPV-RTV were evaluated in a
      randomized, open-label, parallel-group study with 24 healthy human
      immunodeficiency virus type 1-negative adults. Respiratory depression was
      assessed by determination of the ventilatory response to carbon dioxide.
      Tipranavir-containing regimens (LOP-TPV and LOP-TPV-RTV) caused decreases in the
      area under the concentration-time curve from time zero to infinity for LOP (51%
      and 63% decreases, respectively) and its metabolite (72% and 77% decreases,
      respectively), whereas RTV caused increases in the levels of exposure of LOP
      (121% increase) and its metabolite (44% increase). In vitro and in vivo data
      suggest that TPV is a substrate for and an inducer of P-gp activity. The
      respiratory response to LOP in combination with TPV and/or RTV was not different
      from that to LOP alone. There was no evidence that LOP had opioid effects in the
      central nervous system, as measured indirectly by CO2 response curves and
      pupillary response in the presence of TPV and/or RTV.

PMID- 16304150
TI  - Treatment of Candida glabrata infection in immunosuppressed mice by using a
      combination of liposomal amphotericin B with caspofungin or micafungin.
AB  - While Candida albicans remains the most common Candida isolate, Candida glabrata
      accounts for approximately 15 to 20% of all Candida infections in the United
      States. In this study we used immunosuppressed mice infected with C. glabrata to
      investigate the efficacy of liposomal amphotericin B alone or in combination with
      the echinocandin caspofungin or micafungin. For monotherapy, mice were given six
      daily doses of liposomal amphotericin B (3 to 20 mg/kg of body weight),
      caspofungin (1 to 5 mg/kg), or micafungin (2.5 to 10 mg/kg). With concomitant
      therapy, mice received liposomal amphotericin B (7.5 mg/kg) in addition to
      caspofungin (2.5 mg/kg) or micafungin (2.5 mg/kg) for 6 days. For sequential
      therapy, liposomal amphotericin B was administered on days 1 to 3 and caspofungin
      or micafungin was given on days 4 to 6; conversely, caspofungin or micafungin was
      administered on days 1 to 3 and liposomal amphotericin B was given on days 4 to
      6. Efficacy was based on the number of CFU per gram of kidney 21 days
      postchallenge. Monotherapy with liposomal amphotericin B (7.5 to 20 mg/kg) was
      significantly more effective than no drug treatment (control group) (P < 0.05)
      and demonstrated a dose-dependent response, with 20 mg/kg lowering the CFU/g from
      6.3 to 4.2 (significantly different from the value for the control group [P <
      0.001]). Monotherapy with all echinocandin doses lowered the CFU/g from 6.0 to
      6.4 to 2.7 to 3.3 (significantly different from the value for the control group
      [P < 0.001]) with no dose-dependent response. Complete clearance of infection
      could be achieved only when liposomal amphotericin B was given either
      concomitantly with caspofungin or micafungin or if liposomal amphotericin B was
      given sequentially with caspofungin. In conclusion, the combination of liposomal
      amphotericin B with an echinocandin markedly improved the therapeutic outcome in
      murine C. glabrata systemic infection.

PMID- 16304152
TI  - Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with
      potent activity against human immunodeficiency virus type 1.
AB  - Inhibiting human immunodeficiency virus type 1 (HIV-1) infection by blocking the
      host cell coreceptors CCR5 and CXCR4 is an emerging strategy for antiretroviral
      therapy. Currently, several novel coreceptor inhibitors are being developed in
      the clinic, and early results have proven promising. In this report, we describe
      a novel CCR5 antagonist, vicriviroc (formerly SCH-D or SCH 417690), with improved
      antiviral activity and pharmacokinetic properties compared to those of SCH-C, a
      previously described CCR5 antagonist. Like SCH-C, vicriviroc binds specifically
      to the CCR5 receptor and prevents infection of target cells by CCR5-tropic HIV-1
      isolates. In antiviral assays, vicriviroc showed potent, broad-spectrum activity
      against genetically diverse and drug-resistant HIV-1 isolates and was
      consistently more active than SCH-C in inhibiting viral replication. This
      compound demonstrated synergistic anti-HIV activity in combination with drugs
      from all other classes of approved antiretrovirals. Competition binding assays
      revealed that vicriviroc binds with higher affinity to CCR5 than SCH-C.
      Functional assays, including inhibition of calcium flux, guanosine 5'
      [35S]triphosphate exchange, and chemotaxis, confirmed that vicriviroc acts as a
      receptor antagonist by inhibiting signaling of CCR5 by chemokines. Finally,
      vicriviroc demonstrated diminished affinity for the human ether a-go-go related
      gene transcript ion channel compared to SCH-C, suggesting a reduced potential for
      cardiac effects. Vicriviroc represents a promising new candidate for the
      treatment of HIV-1 infection.

PMID- 16304153
TI  - Optimization of meropenem minimum concentration/MIC ratio to suppress in vitro
      resistance of Pseudomonas aeruginosa.
AB  - Suppression of resistance in a dense Pseudomonas aeruginosa population has
      previously been shown with optimized quinolone exposures. However, the relevance
      to beta-lactams is unknown. We investigated the bactericidal activity of
      meropenem and its propensity to suppress P. aeruginosa resistance in an in vitro
      hollow-fiber infection model (HFIM). Two isogenic strains of P. aeruginosa (wild
      type and an AmpC stably derepressed mutant [MIC = 1 mg/liter]) were used. An HFIM
      inoculated with approximately 1 x 10(8) CFU/ml of bacteria was subjected to
      various meropenem exposures. Maintenance doses were given every 8 h to simulate
      the maximum concentration achieved after a 1-g dose in all regimens, but
      escalating unbound minimum concentrations (C(min)s) were simulated with different
      clearances. Serial samples were obtained over 5 days to quantify the meropenem
      concentrations, the total bacterial population, and subpopulations with reduced
      susceptibilities to meropenem (>3x the MIC). For both strains, a significant
      bacterial burden reduction was seen with all regimens at 24 h. Regrowth was
      apparent after 3 days, with the C(min)/MIC ratio being < or = 1.7 (time above the
      MIC, 100%). Selective amplification of subpopulations with reduced
      susceptibilities to meropenem was suppressed with a C(min)/MIC of > or = 6.2 or
      by adding tobramycin to meropenem (C(min)/MIC = 1.7). Investigations that were
      longer than 24 h and that used high inocula may be necessary to fully evaluate
      the relationship between drug exposures and the likelihood of resistance
      suppression. These results suggest that the C(min)/MIC of meropenem can be
      optimized to suppress the emergence of non-plasmid-mediated P. aeruginosa
      resistance. Our in vitro data support the use of an extended duration of
      meropenem infusion for the treatment of severe nosocomial infections in
      combination with an aminoglycoside.

PMID- 16304154
TI  - Antimalarial activities of new pyrrolo[3,2-f]quinazoline-1,3-diamine derivatives.
AB  - WR227825 is an antimalarial pyrroloquinazolinediamine derivative with a high
      potency but a low therapeutic index. A series of carbamate, carboxamide,
      succinimide, and alkylamine derivatives of WR227825 were prepared to search for
      compounds with an improved therapeutic index. The new acetamides and imide showed
      potent cell growth inhibition against four clones of Plasmodium falciparum (D-6,
      RCS, W-2, and TM91C235), with a 50% inhibitory concentration of approximately
      0.01 ng/ml, and were highly active against Plasmodium berghei, with 100% cure at
      doses from <0.1 mg/kg of body weight to 220 mg/kg. The carbamates and alkyl
      derivatives, however, showed weak activity against Plasmodium falciparum cell
      growth but were highly efficacious in tests against P. berghei by the Thompson
      test. The best compounds, bis-ethylcarbamate (compound 2a) and tetra-acetamide
      (3a) derivatives, further demonstrated high potency against the sporozoite
      Plasmodium yoelii in mice and P. falciparum and Plasmodium vivax in aotus
      monkeys. Against the AMRU-1 strain of P. vivax, which has four dihydrofolate
      reductase mutations and is highly resistant to antifolates, tetra-acetamide 3a
      cured the monkeys at doses of 1 and 3 mg/kg. Compound 2a cured only one out of
      two monkeys at 3 mg/kg. The results indicated that the new derivatives 2a and 3a
      not only have retained/improved the antimalarial efficacy of the parent compound
      WR227825 but also were less toxic to the animals used in the tests.

PMID- 16304155
TI  - Population pharmacokinetic analysis of vancomycin in patients with hematological
      malignancies.
AB  - This study determines vancomycin (VAN) population pharmacokinetics (PK) in adult
      patients with hematological malignancies. VAN serum concentration data (n =
      1,004) from therapeutic drug monitoring were collected retrospectively from 215
      patients. A one-compartment PK model was selected. VAN pharmacokinetics
      population parameters were generated using the NONMEM program. A graphic approach
      and stepwise generalized additive modeling were used to elucidate the preliminary
      relationships between PK parameters and clinical covariates analyzed. Covariate
      selection revealed that total body weight (TBW) affected V, whereas renal
      function, estimated by creatinine clearance, and a diagnosis of acute
      myeloblastic leukemia (AML) influenced VAN clearance. We propose one general and
      two AML-specific models. The former was defined by CL (liters/h) = 1.08 x
      CL(CR(Cockcroft and Gault)) (liters/h); CV(CL) = 28.16% and V (liters) = 0.98 x
      TBW; CV(V) =37.15%. AML models confirmed this structure but with a higher
      clearance coefficient (1.17). The a priori performance of the models was
      evaluated in another 59 patients, and clinical suitability was confirmed. The
      models were fairly accurate, with more than 33% of the measured concentrations
      being within +/-20% of the predicted value. This therapeutic precision is twofold
      higher than that of a non-customized population model (16.1%). The corresponding
      standardized prediction errors included zero and a standard deviation close to
      unity. The models could be used to estimate appropriate VAN dosage guidelines,
      which are not clearly defined for this high-risk population. Their simple
      structure should allow easy implementation in clinical software and application
      in dosage individualization using the Bayesian approach.

PMID- 16304156
TI  - Structure-guided discovery of novel aminoglycoside mimetics as antibacterial
      translation inhibitors.
AB  - We report the structure-guided discovery, synthesis, and initial characterization
      of 3,5-diamino-piperidinyl triazines (DAPT), a novel translation inhibitor class
      that targets bacterial rRNA and exhibits broad-spectrum antibacterial activity.
      DAPT compounds were designed as structural mimetics of aminoglycoside antibiotics
      which bind to the bacterial ribosomal decoding site and thereby interfere with
      translational fidelity. We found that DAPT compounds bind to oligonucleotide
      models of decoding-site RNA, inhibit translation in vitro, and induce translation
      misincorporation in vivo, in agreement with a mechanism of action at the
      ribosomal decoding site. The novel DAPT antibacterials inhibit growth of gram
      positive and gram-negative bacteria, including the respiratory pathogen
      Pseudomonas aeruginosa, and display low toxicity to human cell lines. In a mouse
      protection model, an advanced DAPT compound demonstrated efficacy against an
      Escherichia coli infection at a 50% protective dose of 2.4 mg/kg of body weight
      by single-dose intravenous administration.

PMID- 16304157
TI  - Efficacy of orally administered 2-substituted quinolines in experimental murine
      cutaneous and visceral leishmaniases.
AB  - We report in this study the in vivo efficacy of nine 2-substituted quinolines on
      the Leishmania amazonensis cutaneous infection murine model and on the Leishmania
      infantum and Leishmania donovani visceral infection murine models. In the case of
      the L. amazonensis model, quinolines were administered orally at 25 mg/kg twice
      daily for 15 days. Quinolines 1, 2, 3, and 7 reduced by 80 to 90% the parasite
      burdens in the lesion, whereas N-methylglucamine antimoniate (Glucantime),
      administered by subcutaneous injections at 100 mg [28 mg Sb(V)] per kg of body
      weight daily, reduced the parasite burdens by 98%. In visceral leishmaniasis due
      to L. infantum, mice treated orally at 25 mg/kg daily for 10 days with quinolines
      1, 4, 5, and 6 showed a significant reduction of parasite burdens in the liver
      and spleen. These quinolines were significantly more effective than meglumine
      antimoniate to reduce the parasite burden in both the liver and spleen. Also, the
      oral in vivo activity of three quinolines (quinolines 4, 5, and 2-n
      propylquinoline) were determined against L. donovani (LV 9) at 12.5 and 25 mg/kg
      for 10 days. Their activity was compared with that of miltefosine at 7.5 mg/kg.
      Miltefosine, 2-n-propylquinoline, and quinoline 5 at 12.5 mg/kg significantly
      reduced the parasite burdens in the liver by 72, 66, and 61%, respectively. From
      the present study, quinoline 5 is the most promising compound against both
      cutaneous and visceral leishmaniasis. The double antileishmanial and antiviral
      activities of these compounds suggest that this series could be a potential
      treatment for coinfection of Leishmania-human immunodeficiency virus.

PMID- 16304158
TI  - Antimicrobial activities and structures of two linear cationic peptide families
      with various amphipathic beta-sheet and alpha-helical potentials.
AB  - Many naturally occurring antimicrobial peptides comprise cationic linear
      sequences with the potential to adopt an amphipathic alpha-helical conformation.
      We designed a linear 18-residue peptide that adopted an amphipathic beta-sheet
      structure when it was bound to lipids. In comparison to a 21-residue amphipathic
      alpha-helical peptide of equal charge and hydrophobicity, this peptide possessed
      more similar antimicrobial activity and greater selectivity in binding to and
      inducing leakage in vesicles composed of bacterial membrane lipids than vesicles
      composed of mammalian membrane lipids (J. Blazyk, R. Weigand, J. Klein, J.
      Hammer, R. M. Epand, R. F. Epand, W. L. Maloy, and U. P. Kari, J. Biol. Chem.
      276:27899-27906, 2001). Here, we compare two systematically designed families of
      linear cationic peptides to evaluate the importance of amphipathicity for
      determination of antimicrobial activity. Each peptide contains six lysine
      residues and is amidated at the carboxyl terminus. The first family consists of
      five peptides with various capacities to form amphipathic beta-sheet structures.
      The second family consists of six peptides with various potentials to form
      amphipathic alpha helices. Only those peptides that can form a highly amphipathic
      structure (either a beta sheet or an alpha helix) possessed significant
      antimicrobial activities. Striking differences in the abilities to bind to and
      induce leakage in membranes and lipid vesicles were observed for the two
      families. Overall, the amphipathic beta-sheet peptides are less lytic than their
      amphipathic alpha-helical counterparts, particularly toward membranes containing
      phosphatidylcholine, a lipid commonly found in mammalian plasma membranes. Thus,
      it appears that antimicrobial peptides that can form an amphipathic beta-sheet
      conformation may offer a selective advantage in targeting bacterial cells.

PMID- 16304159
TI  - Potent antiviral activity of north-methanocarbathymidine against Kaposi's sarcoma
      associated herpesvirus.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) infection is a prerequisite for
      the development of Kaposi's sarcoma (KS). Blocking lytic KSHV replication may
      hinder KS tumorigenesis. Here, we report potent in vitro anti-KSHV activity of 2'
      exo-methanocarbathymidine [North-methanocarbathymidine (N-MCT)], a thymidine
      analog with a pseudosugar ring locked in the northern conformation, which has
      previously been shown to block the replication of herpes simplex virus types 1
      and 2. N-MCT inhibited KSHV virion production in lytically induced KSHV-infected
      BCBL-1 cells with a substantially lower 50% inhibitory concentration (IC50) than
      those of cidofovir (CDV) and ganciclovir (GCV) (IC50, mean +/- standard
      deviation: 0.08 +/- 0.03, 0.42 +/- 0.07, and 0.96 +/- 0.49 microM for N-MCT, CDV,
      and GCV, respectively). The reduction in KSHV virion production was accompanied
      by a corresponding decrease in KSHV DNA levels in the N-MCT-treated BCBL-1 cells,
      indicating that the compound blocked lytic KSHV DNA replication. A time- and dose
      dependent accumulation of N-MCT-triphosphate (TP) was demonstrated in lytically
      induced BCBL-1 cells, while uninfected cells showed virtually no accumulation.
      The levels of N-MCT-TP were significantly decreased in the presence of 5'
      ethynylthymidine, a potent inhibitor of herpesvirus thymidine kinase, resulting
      in the abrogation of anti-KSHV activity of N-MCT. N-MCT-TP more effectively
      blocked in vitro DNA synthesis by KSHV DNA polymerase with an IC50 of 6.24 +/-
      0.08 microM (mean +/- standard deviation) compared to CDV-diphosphate (14.70 +/
      2.47 microM) or GCV-TP (24.59 +/- 5.60 microM). Taken together, N-MCT is a highly
      potent and target-specific anti-KSHV agent which inhibits lytic KSHV DNA
      synthesis through its triphosphate metabolite produced in KSHV-infected cells
      expressing a virally encoded thymidine kinase.

PMID- 16304160
TI  - Lack of effect of experimental hypovolemia on imipenem muscle distribution in
      rats assessed by microdialysis.
AB  - The aim of this study was to investigate the influence of hypovolemia on the
      distribution of imipenem in muscle extracellular fluid determined by
      microdialysis in awake rats. Microdialysis probes were inserted into the jugular
      vein and hind leg muscle. Imipenem recoveries in muscle and blood were determined
      in each rat by retrodialysis by drug before drug administration. Hypovolemia was
      induced by removing 40% of the initial blood volume over 30 min. Imipenem was
      infused intravenously at a dose of 70 mg . kg(-1) over 30 min, and microdialysis
      samples were collected for 120 min from hypovolemic (n = 8) and control (n = 8)
      rats. The decay of the free concentrations in blood and muscle with time were
      monoexponential, and the concentration profiles in muscle and blood were
      virtually superimposed in both groups. Accordingly, the ratios of the area under
      the concentration-time curve (AUC) for tissue (muscle) to the AUC for blood were
      always virtually equal to 1. Hypovolemia induced a 23% decrease in the clearance
      (P < 0.05) of imipenem, with no statistically significant alteration of its
      volume of distribution. This study showed that imipenem elimination was altered
      in hypovolemic rats, probably due to decreased renal blood flow, but its
      distribution characteristics were not. In particular, free imipenem
      concentrations in blood and muscle were always virtually identical.

PMID- 16304162
TI  - Comparison of the fungicidal activities of caspofungin and amphotericin B against
      Candida glabrata.
AB  - We investigated the fungicidal activity of caspofungin (CAS) and amphotericin B
      (AMB) against 16 clinical isolates of Candida glabrata. The minimum fungicidal
      concentrations (MFCs) of CAS were similar to those of AMB, ranging from 2.0 to
      >8.0 microg/ml. Time-kill assays performed on selected isolates showed that AMB
      was fungicidal at concentrations four times the MIC while CAS was not. A
      neutropenic-mouse model of disseminated infection was utilized to determine the
      residual fungal kidney burden. While doses as low as 0.3 and 1 mg/kg of body
      weight/day of CAS and AMB, respectively, were effective at reducing the counts
      with respect to controls, organ sterilization was reached when both drugs were
      administered at 5 mg/kg/day. Our study reveals that, similar to AMB, CAS has the
      potential for a fungicidal effect in vivo against this difficult-to-treat fungal
      pathogen.

PMID- 16304161
TI  - High-throughput assays using a luciferase-expressing replicon, virus-like
      particles, and full-length virus for West Nile virus drug discovery.
AB  - Many flaviviruses cause significant human disease worldwide. The development of
      flavivirus chemotherapy requires reliable high-throughput screening (HTS) assays.
      Although genetic systems have been developed for many flaviviruses, their usage
      in antiviral HTS assays has not been well explored. Here we compare three cell
      based HTS assays for West Nile virus (WNV) drug discovery: (i) an assay that uses
      a cell line harboring a persistently replicating subgenomic replicon (containing
      a deletion of viral structural genes), (ii) an assay that uses packaged virus
      like particles containing replicon RNA, and (iii) an assay that uses a full
      length reporting virus. A Renilla luciferase gene was engineered into the
      replicon or into the full-length viral genome to monitor viral replication.
      Potential inhibitors could be identified through suppression of luciferase
      signals upon compound incubation. The antiviral assays were optimized in a 96
      well format, validated with known WNV inhibitors, and proved useful in
      identifying a new inhibitor(s) through HTS of a compound library. In addition,
      because each assay encompasses multiple but discrete steps of the viral life
      cycle, the three systems could potentially be used to discriminate the mode of
      action of any inhibitor among viral entry (detected by assays ii and iii but not
      by assay i), replication (including viral translation and RNA synthesis; detected
      by assays i to iii), and virion assembly (detected by assay iii but not by assays
      i and ii). The approaches described in this study should be applicable to the
      development of cell-based assays for other flaviviruses.

PMID- 16304163
TI  - Antibiotic susceptibility testing of Mycoplasma genitalium by TaqMan 5' nuclease
      real-time PCR.
AB  - Mycoplasma genitalium is an important pathogen in male nongonococcal urethritis
      (NGU). Isolation of M. genitalium from clinical specimens by axenic culture is
      very difficult and time-consuming, and very few strains are available for
      antibiotic susceptibility testing. Primary isolation of M. genitalium by
      coculture with Vero cells improves the isolation rate significantly. However,
      some strains cannot be adapted to axenic culture. In this study, we determined
      the antibiotic susceptibility of M. genitalium strains grown in Vero cell culture
      with dilutions of antibiotics. Growth of M. genitalium was monitored by a
      quantitative PCR assay detecting a single-copy region of the mgpB adhesin gene.
      Growth inhibition in the presence of antibiotics was expressed as a percentage of
      the DNA load of controls grown in the absence of antibiotics. Eighteen strains
      were examined, including 6 new strains isolated from urethral swab specimens and
      4 new strains isolated from urine specimens collected from Japanese men. Eight
      strains adapted to axenic culture were also tested by the conventional broth
      dilution method. The two methods had an acceptable correlation. Azithromycin was
      the most active drug against M. genitalium. Among the fluoroquinolones,
      moxifloxacin had the highest activity, with MICs ranging from 0.03 to 0.5
      mg/liter, whereas ciprofloxacin and levofloxacin were considerably less active,
      with MICs ranging from 0.5 to 16 mg/liter and 0.25 to 4 mg/liter, respectively.
      MICs for tetracycline ranged from 0.125 to 4 mg/liter. This new method could
      increase the number of M. genitalium strains available for antibiotic
      susceptibility testing and significantly shorten the time from sampling to MIC
      results.

PMID- 16304164
TI  - Molecular characterization of pneumococci with efflux-mediated erythromycin
      resistance and identification of a novel mef gene subclass, mef(I).
AB  - The molecular genetics of macrolide resistance were analyzed in 49 clinical
      pneumococci (including an "atypical" bile-insoluble strain currently assigned to
      the new species Streptococcus pseudopneumoniae) with efflux-mediated erythromycin
      resistance (M phenotype). All test strains had the mef gene, identified as mef(A)
      in 30 isolates and mef(E) in 19 isolates (including the S. pseudopneumoniae
      strain) on the basis of PCR-restriction fragment length polymorphism analysis.
      Twenty-eight of the 30 mef(A) isolates shared a pulsed-field gel electrophoresis
      (PFGE) type corresponding to the England14-9 clone. Of those isolates, 27 (20
      belonging to serotype 14) yielded multilocus sequence type ST9, and one isolate
      yielded a new sequence type. The remaining two mef(A) isolates had different PFGE
      types and yielded an ST9 type and a new sequence type. Far greater heterogeneity
      was displayed by the 19 mef(E) isolates, which fell into 11 PFGE types, 12
      serotypes (though not serotype 14), and 12 sequence types (including two new ones
      and an undetermined type for the S. pseudopneumoniae strain). In all mef(A)
      pneumococci, the mef element was a regular Tn1207.1 transposon, whereas of the
      mef(E) isolates, 17 carried the mega element and 2 exhibited a previously
      unreported organization, with no PCR evidence of the other open reading frames of
      mega. The mef gene of these two isolates, which did not match with the mef(E)
      gene of the mega element (93.6% homology) and which exhibited comparable homology
      (91.4%) to the mef(A) gene of the Tn1207.1 transposon, was identified as a novel
      mef gene variant and was designated mef(I). While penicillin-nonsusceptible
      isolates (three resistant isolates and one intermediate isolate) were all mef(E)
      strains, tetracycline resistance was also detected in three mef(A) isolates, due
      to the tet(M) gene carried by a Tn916-like transposon. A similar mechanism
      accounted for resistance in four of the five tetracycline-resistant isolates
      carrying mef(E), in three of which mega was inserted in the Tn916-like
      transposon, giving rise to the composite element Tn2009. In the fifth mef(E)
      positive tetracycline-resistant isolate (the S. pseudopneumoniae strain),
      tetracycline resistance was due to the presence of the tet(O) gene, apparently
      unlinked to mef(E).

PMID- 16304165
TI  - Enterococcus faecium low-affinity pbp5 is a transferable determinant.
AB  - Using 15 unrelated Enterococcus faecium isolates as donors, we demonstrated that
      ampicillin resistance was transferable to an E. faecium recipient containing a
      pbp5 deletion for all but four strains. The transfers occurred at low frequencies
      (generally ca. 10(-9) transconjugants/recipient CFU), consistent with chromosome
      to-chromosome transfer. pbp5 transfer occurred within large genetic regions, and
      insertion into the recipient genome occurred most commonly into the recipient
      SmaI restriction fragment that had been created by the previous pbp5 deletion.
      Restriction mapping of the region upstream of pbp5 revealed a commonality of
      fragment sizes among the clinical isolates from the United States which differed
      significantly from those of three strains that were isolated from turkey feces.
      These data prove conclusively that E. faecium pbp5 is a transferable determinant,
      even in the absence of a coresiding vancomycin resistance mobile element. They
      also suggest that the spread of high-level ampicillin resistance among U.S. E.
      faecium strains is due in part to the transfer of low-affinity pbp5 between
      clinical isolates.

PMID- 16304166
TI  - Absolute bioavailability and intracellular pharmacokinetics of azithromycin in
      patients with cystic fibrosis.
AB  - Chronic pulmonary infections with Pseudomonas aeruginosa are the primary cause of
      morbidity and mortality in patients with cystic fibrosis (CF). The macrolide
      antibiotics exhibit immunomodulatory and antivirulence activity. Clinical trials
      with azithromycin in CF have demonstrated significant improvements in pulmonary
      function and decreased hospitalizations. The purpose of this study was to compare
      the pharmacokinetics (PK) of azithromycin in patients with CF and controls. The
      study was conducted as an open-label, parallel, two-period crossover study
      involving 12 healthy volunteers and 12 patients with CF. Period 1 examined the
      serum PK following a single oral and intravenous dose, while period 2 examined
      the intracellular PK following multiple-dose oral administration. CF subjects
      differed significantly from controls based on weight (53.1 versus 71.0 kg; P <
      0.01) and body mass index (19.7 versus 23.2; P < 0.01), respectively. Ninety-two
      percent of CF patients were pancreatic insufficient and were receiving pancreatic
      enzymes. The rate (time to reach maximum serum drug concentration, 3.0 versus 3.0
      h; P = 0.78) and extent of absorption (absolute bioavailability, 34.2 versus
      42.8%; P = 0.37) were similar in patients with CF and controls, respectively.
      Distribution to the tissues (rate of drug transfer from the central to the
      peripheral compartment, 1.22 versus 0.759 h(-1); P = 0.03) and elimination (rate
      of elimination from the central compartment, 0.693 versus 0.492 h(-1); P < 0.01)
      were more rapid in the healthy volunteers than in the CF subjects, respectively.
      Mononuclear cell concentrations (15.2 +/- 6.0 mg/liter) far exceeded the maximum
      serum drug concentration ( approximately 50-fold), demonstrating significant
      intracellular accumulation. These results indicate no alteration in dosage of
      azithromycin is necessary in patients with CF taking pancreatic enzymes.

PMID- 16304167
TI  - Interaction of rifalazil with oxidant-generating systems of human
      polymorphonuclear neutrophils.
AB  - It is well acknowledged that ansamycins display immunosuppressive and anti
      inflammatory properties in vitro and in vivo. Rifalazil, a new ansamycin
      derivative, has not been studied in the context of inflammation. In particular,
      there are no data on the possible interference of rifalazil with oxidant
      production by phagocytes. We have compared the antioxidant properties of
      rifalazil to those of rifampin, a drug well known in this context, by using
      cellular and acellular oxidant-generating systems. Oxidant production by
      polymorphonuclear neutrophils was measured in terms of cytochrome c reduction,
      lucigenin-amplified chemiluminescence (Lu-ACL), and the 2',7'-dichlorofluorescin
      diacetate H2 (DCFDA-H2) technique (intracellular oxidant production). Rifalazil
      impaired O2- production in a concentration-dependent manner, with 50% inhibitory
      concentrations (IC50) (concentrations which inhibit 50% of the response) of 5.4
      (30 and 60 min of incubation) and 6.4 (30 min) mg/liter, respectively, for
      phorbol myristate acetate (PMA) and formyl-methionyl-leucyl-phenylalanine (fMLP)
      stimulation. In agreement with the published fMLP-like activity of rifampin, the
      inhibitory effect of rifampin was significantly greater for fMLP (IC50 of 5.6
      mg/liter) than for PMA (IC50 of 58 mg/liter) stimulation. Alteration of
      intracellular oxidant production was also observed with IC50 values similar to
      those obtained by the cytochrome assay. In addition, rifalazil and rifampin (> or
      = 25 mg/liter) scavenged O2-, as demonstrated by the acellular (hypoxanthine
      xanthine oxidase) system. Interference with light detection systems was evidenced
      for both drugs by Lu-ACL. The clinical relevance of the antioxidant effect of
      rifalazil demonstrated in vitro, in particular its potential anti-inflammatory
      activity, requires further investigation.

PMID- 16304168
TI  - In vitro activity of linezolid against key gram-positive organisms isolated in
      the united states: results of the LEADER 2004 surveillance program.
AB  - Since the approval of linezolid in 2000, sporadic reports of resistance have been
      given and a greater understanding of the underlying mechanisms of resistance has
      been gained. However, since these developments, an updated status of the in vitro
      activity of linezolid against gram-positive organisms from the United States has
      not been reported. The LEADER 2004 surveillance initiative was undertaken to
      obtain current and representative data on the activity of linezolid against key
      species, including isolates with significant resistance phenotypes. Organisms
      were isolated during 2004 and included 2,872 Staphylococcus aureus, 496 coagulase
      negative staphylococcus (CNS), 428 Enterococcus faecalis, 196 Enterococcus
      faecium, and 422 Streptococcus pneumoniae isolates. All S. aureus isolates (54.2%
      oxacillin resistant) were susceptible to linezolid (MIC90 = 2 microg/ml); MIC
      distributions were consistent, regardless of oxacillin or multidrug resistance
      status. For CNS, one nonsusceptible isolate was encountered (Staphylococcus
      epidermidis; MIC = 32 microg/ml), but overall, the MIC(90) (1 microg/ml) was
      lower than that obtained with S. aureus. For E. faecalis and E. faecium, 99.5%
      and 96.4% of isolates, respectively, were linezolid susceptible. Both species had
      an MIC90 of 2 microg/ml, and MIC distributions did not vary with the vancomycin
      susceptibility status of the populations analyzed. Linezolid nonsusceptibility
      was not encountered among the S. pneumoniae isolates. These findings indicate
      that linezolid nonsusceptibility has remained rare among staphylococci and
      uncommon and sporadic among enterococci. Nonetheless, careful and ongoing
      monitoring of the in vitro effectiveness of linezolid will be needed so that any
      changes to the current status may be detected as soon as possible.

PMID- 16304169
TI  - Alternative pathway of metronidazole activation in Trichomonas vaginalis
      hydrogenosomes.
AB  - Metronidazole and related 5-nitroimidazoles are the only available drugs in the
      treatment of human urogenital trichomoniasis caused by the protozoan parasite
      Trichomonas vaginalis. The drugs are activated to cytotoxic anion radicals by
      their reduction within the hydrogenosomes. It has been established that electrons
      required for metronidazole activation are released from pyruvate by the activity
      of pyruvate:ferredoxin oxidoreductase and transferred to the drug by a low-redox
      potential carrier, ferredoxin. Here we describe a novel pathway involved in the
      drug activation within the hydrogenosome. The source of electrons is malate,
      another major hydrogenosomal substrate, which is oxidatively decarboxylated to
      pyruvate and CO2 by NAD-dependent malic enzyme. The electrons released during
      this reaction are transferred from NADH to ferredoxin by NADH dehydrogenase
      homologous to the catalytic module of mitochondrial complex I, which uses
      ferredoxin as electron acceptor. Trichomonads acquire high-level metronidazole
      resistance only after both pyruvate- and malate-dependent pathways of
      metronidazole activation are eliminated from the hydrogenosomes.

PMID- 16304170
TI  - Novel cyclic lipodepsipeptide from Pseudomonas syringae pv. lachrymans strain 508
      and syringopeptin antimicrobial activities.
AB  - The syringopeptins are a group of antimicrobial cyclic lipodepsipeptides produced
      by several plant-associated pseudomonads. A novel syringopeptin, SP508, was shown
      to be produced as two homologs (A and B) by Pseudomonas syringae pv. lachrymans
      strain 508 from apple and to structurally resemble syringopeptin SP22. SP508
      differed from SP22 and other syringopeptins by having three instead of four
      alpha,beta-unsaturated amino acids and a longer beta-hydroxy acyl chain. Both
      SP508 and SP22 displayed growth-inhibitory activities against Mycobacterium
      smegmatis, other gram-positive bacteria, and yeasts but not against gram-negative
      bacteria. Structure-activity analyses of the SP508 and SP22 homologs indicated
      chemical structural features that lead to enhanced antimycobacterial activity by
      these pseudomonad cyclic lipodepsipeptides.

PMID- 16304171
TI  - Vancomycin-resistant Enterococcus faecium: catheter colonization, esp gene, and
      decreased susceptibility to antibiotics in biofilm.
AB  - To evaluate the molecular characteristics and antibiotic susceptibility in
      biofilm of vancomycin-resistant Enterococcus faecium (VREF) organisms that had
      caused catheter-related VREF bacteremia (VREF-CRB), we compared 22 isolates
      causing bacteremia obtained from patients with VREF-CRB with 30 isolates from
      control patients with gastrointestinal colonization by VREF. Using pulsed-field
      gel electrophoresis, we identified 17 unique strains among the 22 VREF-CRB
      isolates and 23 strains among the gastrointestinal isolates. The esp gene was
      detected in 53% (9 of 17) of the VREF-CRB and 61% (14 of 23) of the control
      strains (P = 0.6). VREF-CRB produced heavier biofilm colonization of silicone
      disks than did control organisms (P < 0.001). Daptomycin, minocycline, and
      quinupristin-dalfopristin were each independently more active than linezolid in
      reducing biofilm colonization by VREF-CRB (P < 0.01), with daptomycin being the
      most active, followed by minocycline. In conclusion, the esp gene in VREF is not
      associated with heavy biofilm colonization or catheter-related bacteremia. In
      biofilm, daptomycin and minocycline were the most active antibiotics against
      VREF, and linezolid was the least active.

PMID- 16304172
TI  - DX-619, a novel des-fluoro(6) quinolone manifesting low frequency of selection of
      resistant Staphylococcus aureus mutants: quinolone resistance beyond modification
      of type II topoisomerases.
AB  - DX-619, a novel des-fluoro(6) quinolone, was 16- to 32-fold, twofold, and four-
      to eightfold more potent than ciprofloxacin, gemifloxacin, and garenoxacin,
      respectively, against wild-type Staphylococcus aureus. DX-619 manifested equal
      fourfold increases in MIC against a common parC mutant and a common gyrA mutant
      and selected for mutants at up to two- to fourfold its MIC, consistent with dual
      targeting properties. Of the four independent single-step mutants selected, two
      had new single mutations in parC (V87F and R17H), and two shared a new gyrA
      mutation (A26V), one with an additional deletion mutation in parE (delta215-7).
      By allelic exchange, the ParC but not the GyrA or ParE mutation was shown to be
      fully responsible for the resistance phenotypes, suggesting an as yet undefined
      mechanism of resistance operating in conjunction with type II topoisomerase
      mutations contributed to resistance to DX-619. Studies with purified
      topoisomerase IV and gyrase from S. aureus also showed that DX-619 had similar
      activity against topoisomerase IV and gyrase (50% stimulation of cleavage
      complexes concentration, 1.25 and 0.62 to 1.25 mug/ml, respectively).
      Susceptibility studies with DX-619 and an array of efflux pump substrates with
      and without reserpine, an inhibitor of efflux pumps, suggested that resistance in
      DX-619-selected mutants is affected by mechanisms other than mutations in
      topoisomerases or known reserpine-inhibitable pumps in S. aureus and thus are
      likely novel.

PMID- 16304173
TI  - Pharmacodynamics of caspofungin in a murine model of systemic candidiasis:
      importance of persistence of caspofungin in tissues to understanding drug
      activity.
AB  - Pharmacokinetic and pharmacodynamic studies were conducted in a murine model of
      systemic candidiasis to determine the pharmacodynamic parameter linked with
      caspofungin efficacy. Additional studies defined the importance of persistent
      tissue drug concentrations to treatment outcome. The pharmacokinetics of
      caspofungin were determined in the serum and kidneys of infected mice over 96 h.
      Population pharmacokinetic analysis demonstrated a serum terminal half-life
      (t(1/2)) for caspofungin of 20.2 h when only serum concentrations were
      considered, but the terminal t(1/2) increased to 59.2 h when serum and kidney
      concentration-time data were co-modeled. In dose-range studies, the dose-response
      effect was well described by an inhibitory sigmoid curve for the exposure-effect
      killing caused by the drug (r2 > 0.96; P << 0.001). In dose-fractionation
      studies, fungal counts in kidneys were not statistically different for total
      doses given as one, two, or four equally divided doses over 96 h, indicating that
      the area under the concentration-time curve/MIC is the pharmacodynamic parameter
      that predicts caspofungin efficacy in our infection model. In a separate study,
      mice infected with Candida albicans 24 h after serum concentrations of
      caspofungin fell below the MIC for the fungal isolate had significant reductions
      in fungal densities in their kidneys compared with the growth of fungi in the
      kidneys of untreated controls (P = 0.005). This in vivo biological assay
      demonstrates that therapeutic concentrations of caspofungin persist at the site
      of infection in kidney tissue well after serum concentrations fall below the MIC,
      underscoring the primacy of caspofungin levels in tissues on determining
      treatment outcome.

PMID- 16304174
TI  - Erythromycin resistance and genetic elements carrying macrolide efflux genes in
      Streptococcus agalactiae.
AB  - The macrolide resistance determinants and genetic elements carrying the mef(A)
      and mef(E) subclasses of the mef gene were studied with Streptococcus agalactiae
      isolated in 2003 and 2004 from 7,084 vaginorectal cultures performed to detect
      carrier pregnant women. The prevalence of carriage was 18% (1,276 isolates), and
      that of erythromycin resistance 11.0% (129 of the 1,171 isolates studied).
      erm(B), erm(A) subclass erm(TR), and the mef gene, either subclass mef(A) or
      mef(E), were found in 72 (55.8%), 41 (31.8%), and 12 (9.3%) erythromycin
      resistant isolates, while 4 isolates had more than 1 erythromycin resistance
      gene. Of the 13 M-phenotype mef-containing erythromycin-resistant S. agalactiae
      isolates, 11 had the mef(E) subclass gene alone, one had both the mef(E) and the
      erm(TR) subclass genes, and one had the mef(A) subclass gene. mef(E) subclass
      genes were associated with the carrying element mega in 10 of the 12 mef(E)
      containing strains, while the single mef(A) subclass gene found was associated
      with the genetic element Tn1207.3. The nonconjugative nature of the mega element
      and the clonal diversity of mef(E)-containing strains determined by pulsed-field
      gel electrophoresis suggest that transformation is the main mechanism through
      which this resistance gene is acquired.

PMID- 16304175
TI  - Beta-lactam resistance in Staphylococcus aureus cells that do not require a cell
      wall for integrity.
AB  - Staphylococcus aureus ATCC 9144 cells with defective cell walls were generated on
      a medium with elevated osmolality in the presence of sublethal levels of
      penicillin G. On removal of antibiotic pressure, the cells exhibited stable
      penicillin and methicillin resistance. The resistance was homogeneous and its
      acquisition was enhanced following transient cell wall-defective growth. The
      resistant cells were mecA negative, beta-lactamase negative and did not contain
      any mutations in the coding regions of pbp genes. When penicillin was added back
      to resistant cells, they continued to grow and produced a diffuse cell wall that
      was resistant to the action by lysostaphin but was very sensitive to lysis with
      Triton X-100. These data indicate that the resistant cells are not dependent upon
      an intact cell wall for osmotic stability and they are able to switch readily to
      this mode of growth in the presence of penicillin G.

PMID- 16304176
TI  - Pharmacodynamic model to describe the concentration-dependent selection of
      cefotaxime-resistant Escherichia coli.
AB  - Antibiotic dosing regimens may vary in their capacity to select mutants. Our
      hypothesis was that selection of a more resistant bacterial subpopulation would
      increase with the time within a selective window (SW), i.e., when drug
      concentrations fall between the MICs of two strains. An in vitro kinetic model
      was used to study the selection of two Escherichia coli strains with different
      susceptibilities to cefotaxime. The bacterial mixtures were exposed to cefotaxime
      for 24 h and SWs of 1, 2, 4, 8, and 12 h. A mathematical model was developed that
      described the selection of preexisting and newborn mutants and the post-MIC
      effect (PME) as functions of pharmacokinetic parameters. Our main conclusions
      were as follows: (i) the selection between preexisting mutants increased with the
      time within the SW; (ii) the emergence and selection of newborn mutants increased
      with the time within the SW (with a short time, only 4% of the preexisting
      mutants were replaced by newborn mutants, compared to the longest times, where
      100% were replaced); and (iii) PME increased with the area under the
      concentration-time curve (AUC) and was slightly more pronounced with a long
      elimination half-life (T(1/2)) than with a short T(1/2) situation, when AUC is
      fixed. We showed that, in a dynamic competition between strains with different
      levels of resistance, the appearance of newborn high-level resistant mutants from
      the parental strains and the PME can strongly affect the outcome of the selection
      and that pharmacodynamic models can be used to predict the outcome of resistance
      development.

PMID- 16304177
TI  - Population pharmacokinetics of amphotericin B lipid complex in neonates.
AB  - The pharmacokinetics of amphotericin B lipid complex (ABLC) were investigated in
      neonates with invasive candidiasis enrolled in a phase II multicenter trial.
      Sparse blood (153 samples; 1 to 9 per patient, 1 to 254 h after the dose) and
      random urine and cerebrospinal fluid (CSF) samples of 28 neonates (median weight
      [WT], 1.06 kg; range, 0.48 to 4.9 kg; median gestational age, 27 weeks; range, 24
      to 41 weeks) were analyzed. Patients received intravenous ABLC at 2.5 (n = 15) or
      5 (n = 13) mg/kg of body weight once a day over 1 or 2 h, respectively, for a
      median of 21 days (range, 4 to 47 days). Concentrations of amphotericin B were
      quantified as total drug by high-performance liquid chromatography. Blood data
      for time after dose (TAD) of <24 h fitted best to a one-compartment model with an
      additive-error model for residual variability, WT0.75 (where 0.75 is an exponent)
      as a covariate of clearance (CL), and WT as a covariate of volume of distribution
      (V). Prior amphotericin B, postnatal age, and gestational age did not further
      improve the model. The final model equations were CL (liters/h) = 0.399 x
      WT(0.75) (interindividual variability, 35%) and V (liters) = 10.5 x WT
      (interindividual variability, 43%). Noncompartmental analysis of pooled data with
      a TAD of >24 h revealed a terminal half-life of 395 h. Mean concentrations in the
      urine after 1, 2, and 3 weeks ranged from 0.082 to 0.430 microg/ml, and those in
      CSF ranged from undetectable to 0.074 microg/ml. The disposition of ABLC in
      neonates was similar to that observed in other age groups: weight was the only
      factor that influenced clearance. Based on these results and previously published
      safety and efficacy data, we recommend a daily dosage between 2.5 and 5.0 mg/kg
      for treatment of invasive Candida infections in neonates.

PMID- 16304178
TI  - Effective antimicrobial regimens for use in humans for therapy of Bacillus
      anthracis infections and postexposure prophylaxis.
AB  - Expanded options for treatments directed against pathogens that can be used for
      bioterrorism are urgently needed. Treatment regimens directed against such
      pathogens can be identified only by using data derived from in vitro and animal
      studies. It is crucial that these studies reliably predict the efficacy of
      proposed treatments in humans. The objective of this study was to identify a
      levofloxacin treatment regimen that will serve as an effective therapy for
      Bacillus anthracis infections and postexposure prophylaxis. An in vitro hollow
      fiber infection model that replicates the pharmacokinetic profile of levofloxacin
      observed in humans (half-life [t(1/2)], 7.5 h) or in animals, such as the mouse
      or the rhesus monkey (t(1/2), approximately 2 h), was used to evaluate a proposed
      indication for levofloxacin (500 mg once daily) for the treatment of Bacillus
      anthracis infections. The results obtained with the in vitro model served as the
      basis for the doses and the dose schedules that were evaluated in the mouse
      inhalational anthrax model. The effects of levofloxacin and ciprofloxacin
      treatment were compared to those of no treatment (untreated controls). The main
      outcome measure in the in vitro hollow-fiber infection model was a persistent
      reduction of culture density (> or = 4 log10 reduction) and prevention of the
      emergence of levofloxacin-resistant organisms. In the mouse inhalational anthrax
      model the main outcome measure was survival. The results indicated that
      levofloxacin given once daily with simulated human pharmacokinetics effectively
      sterilized Bacillus anthracis cultures. By using a simulated animal
      pharmacokinetic profile, a once-daily dosing regimen that provided a human
      equivalent exposure failed to sterilize the cultures. Dosing regimens that
      "partially humanized" levofloxacin exposures within the constraints of animal
      pharmacokinetics reproduced the antimicrobial efficacy seen with human
      pharmacokinetics. In a mouse inhalational anthrax model, once-daily dosing was
      significantly inferior (survival end point) to regimens of dosing every 12 h or
      every 6 h with identical total daily levofloxacin doses. These results
      demonstrate the predictive value of the in vitro hollow-fiber infection model
      with respect to the success or the failure of treatment regimens in animals.
      Furthermore, the model permits the evaluation of treatment regimens that
      "humanize" antibiotic exposures in animal models, enhancing the confidence with
      which animal models may be used to reliably predict the efficacies of proposed
      antibiotic treatments in humans in situations (e.g., the release of pathogens as
      agents of bioterrorism or emerging infectious diseases) where human trials cannot
      be performed. A treatment regimen effective in rhesus monkeys was identified.

PMID- 16304179
TI  - In vivo measurement of levofloxacin penetration into lung tissue after cardiac
      surgery.
AB  - Nosocomial pneumonia is a severe complication after cardiac surgery (CS).
      Levofloxacin, a fluoroquinolone, qualifies for the therapy of postoperative
      pneumonia. However, penetration properties of levofloxacin into the lung tissue
      could be substantially affected by CS: atelectasis, low cardiac output after CS,
      high volume loads, and inflammatory capillary leak potentially influence drug
      distribution. The aim of our study was to gain information on interstitial
      antibiotic concentrations in lung tissue in patients undergoing coronary artery
      bypass grafting with cardiopulmonary bypass. Therefore, six patients undergoing
      elective CS participated in this prospective study. A dose of 500 mg of
      levofloxacin was administered intravenously in addition to standard antibiotic
      prophylaxis immediately after the end of surgery. Time versus concentration
      profiles of levofloxacin in the interstitial lung tissue and plasma were
      determined. A microdialysis technique was used for lung interstitial
      concentration measurements. The microdialysis procedure was well tolerated in all
      patients and no adverse events were observed. The median area under the
      concentration curve (AUC) of levofloxacin in interstitial lung fluid was 18.6
      microg.h/ml (range, 10.1 to 33.6). The median AUC for tissue (AUC(tissue)) of
      unbound levofloxacin/AUC(total) in plasma was 0.6 (range, 0.4 to 0.9). The median
      unbound AUC(tissue)/MIC was 2.4 (range, 1.3 to 4.2) for Pseudomonas aeruginosa.
      Our study demonstrated the feasibility and safety of microdialysis in human lung
      tissue in vivo after CS. The unbound AUC/MIC ratio revealed that levofloxacin
      used in the described manner was borderline sufficient for the treatment of
      nosocomial pneumonia caused by Klebsiella pneumoniae and insufficient for the
      treatment of pneumonia caused by Pseudomonas aeruginosa, because the breakpoint
      of 30 to 40 for AUC/MIC could not be reached by the conventionally used dosage
      schema in our post-CS setting. Penetration was lower than in previous reports.

PMID- 16304180
TI  - Analysis of the contribution of individual substituents in 4,6-aminoglycoside
      ribosome interaction.
AB  - The 4,6-disubstituted 2-deoxystreptamines interfere with protein biosynthesis by
      specifically targeting the ribosomal A site. These drugs show subtle variations
      in the chemical groups of rings I, II, and III. In the present study we used site
      directed mutagenesis to generate mutant strains of Mycobacterium smegmatis
      mc(2)155 SMR5 DeltarrnB with mutations in its single rRNA allele, rrnA. This
      genetic procedure gives rise to strains carrying homogeneous populations of
      mutant ribosomes and was used to study the contribution of individual chemical
      substituents to the binding of 4,6-disubstituted aminoglycosides. X-ray crystal
      structures of geneticin and tobramycin complexed to oligonucleotides containing
      the minimal bacterial ribosomal A site were used for interpretation of MICs
      determined for a panel of 4,6-aminoglycosides, including tobramycin, kanamycin A,
      kanamycin B, amikacin, gentamicin, and geneticin. Surprisingly, the considerable
      differences present within ring III did not seem to alter the interaction of the
      drug with the ribosome, as determined by site-directed mutagenesis of the A site.
      In contrast, subtle variations in ring I significantly influenced binding: (i) a
      4'-hydroxyl moiety participates in the proper drug target interaction; and (ii) a
      2'-amino group contributes an additional positive charge to ring I, making the
      drug less susceptible to any kind of sequence alteration within the decoding
      site, most notably, to conformational changes induced by transversion of U1495 to
      1495A. The 4-amino-2-hydroxyl-1-oxobutyl extension at position 1 of ring II of
      amikacin provides an additional anchor and renders amikacin less dependent on the
      structural conformation of nucleotide U1406 compared to the dependencies of other
      kanamycins. Overall, the set of interactions forming the complex between drug
      substituents and nucleotides of the A site constitutes a network in which the
      interactions can partly compensate for each other when they are disrupted.

PMID- 16304181
TI  - Moxifloxacin and azithromycin but not amoxicillin protect human respiratory
      epithelial cells against streptococcus pneumoniae in vitro when administered up
      to 6 hours after challenge.
AB  - We determined the protective effect of moxifloxacin, azithromycin, and
      amoxicillin against Streptococcus pneumoniae infection of respiratory cells.
      Moxifloxacin and azithromycin effectively killed intracellular S. pneumoniae
      strains and protected respiratory epithelial cells significantly even when given
      6 h after S. pneumoniae challenge. Amoxicillin was less effective.

PMID- 16304182
TI  - Antichagasic activity of komaroviquinone is due to generation of reactive oxygen
      species catalyzed by Trypanosoma cruzi old yellow enzyme.
AB  - A novel potent trypanocidal diterpene, komaroviquinone, was reduced by
      Trypanosoma cruzi old yellow enzyme (TcOYE) to its semiquinone radical. The
      reductase activity in trypanosome lysates was completely immunoabsorbed by anti
      TcOYE antibody. Since TcOYE is expressed throughout the T. cruzi life cycle,
      komaroviquinone is an interesting candidate for developing new antichagasic
      drugs.

PMID- 16304183
TI  - Pitfalls in estimating piperaquine elimination.
AB  - By using a sensitive new assay, the terminal elimination half-life of the
      antimalarial piperaquine in a healthy volunteer was estimated to be 33 days,
      which is longer than estimated previously. This result illustrates the importance
      of extended sampling duration and sensitive assay methodologies in characterizing
      the disposition of slowly eliminated antimalarial drugs.

PMID- 16304184
TI  - Type V staphylococcal cassette chromosome mec in community staphylococci from
      Australia.
AB  - Twenty Australian community staphylococci harboring the type V staphylococcal
      cassette chromosome mec (SCCmec) were found to belong to eight multilocus
      sequence types. Five were previously unreported novel type V SCCmec elements. The
      mec complexes were of two types, based on the polymorphisms in the IS431
      transposase genes. Five isolates were multiresistant.

PMID- 16304185
TI  - Efficacy of caspofungin against Aspergillus terreus.
AB  - We investigated the in vitro and in vivo activities of caspofungin against
      Aspergillus terreus. The drug increased survival and reduced tissue fungal burden
      in neutropenic mice. Therefore, our data support the role of caspofungin in
      treating systemic infections due to this emerging pathogen.

PMID- 16304186
TI  - In vitro activity of ravuconazole against 923 clinical isolates of
      nondermatophyte filamentous fungi.
AB  - The in vitro activities of ravuconazole against 575 clinical strains of
      Aspergillus spp. and 348 nondermatophyte non-Aspergillus spp. were analyzed.
      Ravuconazole was active against Aspergillus spp., other hyaline filamentous
      fungi, black molds, and some Mucorales. Species such as Scedosporium prolificans,
      Fusarium spp., and Scopulariopsis spp. were resistant to the triazole.

PMID- 16304187
TI  - Caspofungin and liposomal amphotericin B therapy of experimental murine
      scedosporiosis.
AB  - Immunosuppressed mice were infected intravenously with conidia of Scedosporium
      prolificans. Treatment was begun 1 day later with liposomal amphotericin B,
      caspofungin, or both drugs initiated concurrently. Amphotericin B and caspofungin
      were each effective, but combined therapy did not appear to offer advantages over
      liposomal amphotericin B alone.

PMID- 16304188
TI  - Horizontal transfer of erythromycin resistance from Clostridium difficile to
      Butyrivibrio fibrisolvens.
AB  - This study demonstrates for the first time the in vitro transfer of the
      erythromycin resistance gene erm(B) between two obligate anaerobes, the human
      spore-forming pathogen Clostridium difficile and the rumen commensal Butyrivibrio
      fibrisolvens, suggesting that this event might occur also in the natural
      environment.

PMID- 16304189
TI  - Attenuation of the activity of caspofungin at high concentrations against candida
      albicans: possible role of cell wall integrity and calcineurin pathways.
AB  - Caspofungin had diminished activity in vitro against Candida albicans at
      concentrations of 8 to 32 microg/ml. This phenomenon was markedly attenuated in a
      deltamkc1/deltamkc1 deletion mutant and by the addition of cyclosporine to the
      wild type. Short exposure to these caspofungin concentrations resulted in MKC1 up
      regulation, suggesting roles of cell wall integrity and calcineurin pathways.

PMID- 16304190
TI  - Variants of the Klebsiella pneumoniae OKP chromosomal beta-lactamase are divided
      into two main groups, OKP-A and OKP-B.
AB  - Two bla(OKP) subgroups were found, diverging by 4.2%. Subgroups bla(OKP-A) (10
      enzyme variants, pIs from 7.1 to 8.3) and bla(OKP-B) (11 variants, pI 7.1) showed
      similar antibiotic susceptibilities. Sequencing of rpoB, gyrA, and mdh
      demonstrated a concordant subdivision of Klebsiella pneumoniae phylogenetic group
      KpII into two subgroups, KpII-A and KpII-B.

PMID- 16304191
TI  - VIM-12, a novel plasmid-mediated metallo-beta-lactamase from Klebsiella
      pneumoniae that resembles a VIM-1/VIM-2 hybrid.
AB  - A transferable plasmid from Klebsiella pneumoniae carried a class 1 integron
      containing bla(VIM-12), a novel bla(VIM)-type gene, flanked by two copies of
      aacA7. bla(VIM-12) was clustered between bla(VIM-1) and bla(VIM-2) and differed
      from bla(VIM-1) by 18 nucleotides that were all located at the 3' end and matched
      the corresponding nucleotides in bla(VIM-2). The bla(VIM-12)-associated 59-base
      element was identical to that described in bla(VIM-2) alleles.

PMID- 16304192
TI  - Effect of voriconazole combined with micafungin against Candida, Aspergillus, and
      Scedosporium spp. and Fusarium solani.
AB  - Effects of voriconazole combined with micafungin against 101 isolates of Candida
      spp. and 100 isolates of filamentous fungi have been evaluated by in vitro
      checkerboard analysis. The combination was indifferent for 97% of the Candida
      isolates and synergistic for 64% of the filamentous fungi (79% for Aspergillus
      fumigatus).

PMID- 16304193
TI  - A cysteine protease inhibitor protects dogs from cardiac damage during infection
      by Trypanosoma cruzi.
AB  - Cruzain is an essential cysteine protease of Trypanosoma cruzi and a therapeutic
      target for Chagas' disease. Eight dogs were infected with T. cruzi; three were
      treated with an inhibitor of cruzain, K777, for 14 days. Treatment with K777
      abrogated myocardial damage by T. cruzi, as documented by histopathological
      lesion scores and serum troponin I levels.

PMID- 16304194
TI  - Assessing the in vitro effectiveness of antimicrobials against Mycoplasma
      mycoides subsp. mycoides small-colony type to reduce contagious bovine
      pleuropneumonia infection.
AB  - In vitro minimum inhibitory concentrations were determined for 21 antimicrobials
      against 41 isolates of Mycoplasma mycoides subsp. mycoides small-colony type, the
      cause of contagious bovine pleuropneumonia. Of the antimicrobials used most
      widely in Africa, oxytetracycline and tilmicosin were effective, while the
      isolates were resistant to tylosin. These results provide a baseline for
      monitoring antimicrobial resistance.

PMID- 16304195
TI  - In vitro synergy of daptomycin plus rifampin against Enterococcus faecium
      resistant to both linezolid and vancomycin.
AB  - In vitro synergy testing of daptomycin plus rifampin was performed against 24
      unique isolates of Enterococcus faecium resistant to both linezolid and
      vancomycin. Synergy testing showed that 21/24 (88%) were synergistic and 3/24
      (12%) were indifferent by the Etest method. Time-kill assays revealed synergy for
      18/24 (75%) and indifference for 6/24 (25%).

PMID- 16304196
TI  - Interaction of monobenzamidine-linked trypanocides with the Trypanosoma brucei P2
      aminopurine transporter.
AB  - Single benzamidine group-carrying compounds were shown to interact with the
      Trypanosoma brucei P2 aminopurine transporter. Replacement of the amidine with a
      guanidine group decreased affinity. Trypanocidal activity was evident, but
      compounds were equally toxic against trypanosomes lacking the P2 transporter,
      which indicates additional uptake routes for monobenzamidine-derived compounds.

PMID- 16304197
TI  - Cloning and functional analysis of the gene encoding the 33- to 36-kilodalton
      outer membrane protein associated with carbapenem resistance in Acinetobacter
      baumannii.
AB  - We investigated a multiresistant strain of Acinetobacter baumannii isolated in
      our hospital. Analysis of the N-terminal peptide sequence of the outer membrane
      proteins (OMPs) purified from the strain allowed us to clone and sequence the
      nucleotides of the gene encoding the 33- to 36-kDa OMP associated with carbapenem
      resistance in A. baumannii.

PMID- 16304198
TI  - High rate of resistance to quinupristin-dalfopristin in Enterococcus faecium
      clinical isolates from Korea.
AB  - We tested the in vitro susceptibilities of 603 enterococcal isolates from eight
      tertiary-care hospitals in Korea. The quinupristin-dalfopristin resistance rate
      in Enterococcus faecium was very high (25 isolates, 10.0%). It was suggested that
      both clonal spread and the sporadic emergence of quinupristin-dalfopristin
      resistant isolates may explain the high prevalence of quinupristin-dalfopristin
      resistance in Korea.

PMID- 16304199
TI  - Novel rearrangement of a class 2 integron in two non-epidemiologically related
      isolates of Acinetobacter baumannii.
AB  - Tn7::In2-8 contains sat2-aadB-catB2(deltaattC)-dfrA1-sat2-aadA1-orfX in the
      variable region of a class 2 integron embedded in the Tn7-like transposon. This
      novel transposon was inserted in its preferred site downstream of the glms gene
      in Acinetobacter baumannii. Acquisition of the pseudocassette catB2 could have
      arisen by a secondary-site integrase-mediated intermolecular recombination event.

PMID- 16304200
TI  - Antipneumococcal activity of dalbavancin compared to other agents.
AB  - Against 307 pneumococci of various resistotypes, dalbavancin MICs were 0.008 to
      0.125 microg/ml. All strains were susceptible to vancomycin, teicoplanin,
      linezolid, and quinupristin-dalfopristin. Dalbavancin at 2x MIC was bactericidal
      against all 10 pneumococci tested after 24 h. Vancomycin and teicoplanin killed
      10 and 8 strains, respectively, at 2x MIC after 24 h.

PMID- 16304201
TI  - Human immunodeficiency virus type 1 latency model for high-throughput screening.
AB  - Human immunodeficiency virus type 1 (HIV-1) is not eliminated from patients even
      after years of antiretroviral therapy, apparently due to the presence of latently
      infected cells. Here we describe the development of a cell-based system of
      latency that can be used for high-throughput screening aimed at novel drug
      discovery to eradicate HIV-1 infection.

PMID- 16304202
TI  - Levofloxacin and moxifloxacin increase human gut colonization by Candida species.

PMID- 16304203
TI  - Orally administered recombinant metallo-beta-lactamase preserves colonization
      resistance of piperacillin-tazobactam-treated mice.

PMID- 16304204
TI  - Influence of a leptin deficiency on testicular morphology, germ cell apoptosis,
      and expression levels of apoptosis-related genes in the mouse.
AB  - Leptin-deficient (ob/ob) male mice are morbidly obese and exhibit impaired
      reproductive function. The objective of this study was to assess the effect of a
      leptin deficiency on testicular morphology, germ cell development, apoptotic
      activity within germ cells, and expression levels of apoptosis-related genes in
      the testis. Sixteen week-old ob/ob male mice (n = 8) and controls (n = 8) were
      killed, and their reproductive organs were weighed. Testes were processed for
      either histomorphological analysis (hematoxylin and eosin [H&E] staining), germ
      cell apoptosis assessment (deoxy-UTP-digoxigenin nick end labeling [TUNEL]
      method), or apoptosis-related gene expression analysis (microarray). Cross
      sections of the testes of leptin-deficient animals showed reduced seminiferous
      tubule area, fewer pachytene spermatocytes, and fewer tubules exhibiting
      elongated spermatids/mature spermatozoa. Condensation of germ cell nuclei and
      Sertoli cell vacuolization were evident in the testes of some ob/ob animals.
      Overall there was an elevation of apoptotic activity in the germ cells of ob/ob
      mice, particularly within the pachytene spermatocytes. With microarray
      technology, we identified 9 proapoptosis-related genes that were expressed at a
      significantly higher level in the testes of ob/ob mice than in the testes of the
      controls. Among these were members of the tumor necrosis factor receptor super
      family 1A and 5 (TNFR1 and 5) and peptidoglycan recognition proteins (associated
      with the extrinsic apoptotic pathway), and granzymes A and B, growth arrest and
      DNA damage inducible 45 gamma, sphingosine phosphate lyase 1, and caspase 9
      (associated with the intrinsic apoptotic pathway). The results of the current
      study show that a leptin deficiency in mice is associated with impaired
      spermatogenesis, increased germ cell apoptosis, and up-regulated expression of
      proapoptotic genes within the testes.

PMID- 16304205
TI  - Relationship of cytoplasmic droplets to motility, migration in mucus, and volume
      regulation of human spermatozoa.
AB  - A significantly greater percentage of motile than immotile spermatozoa bore
      droplets at the osmolality of semen and cervical mucus. The percentage of
      spermatozoa with droplets was not significantly correlated with the osmolality of
      semen or the extent of cell swelling in response to quinine in hypotonic medium.
      Droplets appeared slightly more frequently (ie, were more obvious) in the
      presence of quinine, which blocks regulatory volume decrease, indicating that
      they are the major site of volume expansion. There was no selection for or
      against droplet-bearing spermatozoa migrating through viscous surrogate mucus at
      high or low osmolality. Sperm swelling in response to quinine at mucus osmolality
      was significantly greater in fathers than in patients whose partners had no
      fertility problem. Therefore, cytoplasmic droplets are not deleterious to sperm
      motility and may be related to physiological volume regulation, which may be
      predictive of some forms of human male infertility.

PMID- 16304206
TI  - Influence of sperm pretreatment on the efficiency of intracytoplasmic sperm
      injection in pigs.
AB  - The purpose of this study was to determine the influence of sperm pretreatment on
      the efficiency of intracytoplasmic sperm injection (ICSI) in pigs. This was done
      by examining the effect of 1) the conservation method (fresh vs frozen); 2) the
      sperm treatment preinjection (resuspension in Dulbecco phosphate-buffered saline
      (DPBS) vs selection by a Percoll gradient); and 3) the acrosomal and live or dead
      status of the spermatozoa (by incubation with or without calcium ionophore, 1 muM
      and 5 muM). In vitro matured porcine oocytes were injected with treated
      spermatozoa according to each experiment. All the experiments were done with non
      artificially activated oocytes. The percentages of activation and cleavage were
      higher (68% vs 43% and 63% vs 43%, respectively, P < .05) in oocytes injected
      with fresh vs frozen spermatozoa. The DPBS treatment allowed higher cleavage
      proportions than the Percoll treatment (P < .05). Moreover, a boar effect was
      observed in the percentage of developing blastocysts. None of the studied
      parameters was affected by the acrosomal or the live or dead status of the
      spermatozoa injected. In conclusion, the use of fresh semen is recommended for
      porcine ICSI, as well as careful selection of the boar; Percoll treatment is only
      recommended for poor-quality samples or for removing toxic agents, and no
      exogenous form of activation or induction of the acrosome reaction is necessary
      for porcine oocytes to develop a male pronucleus and cleave up to the 2-cell
      stage after ICSI, although experimental conditions to reach the blastocyst stage
      need to be investigated further.

PMID- 16304207
TI  - Expression, localization, and regulation of inhibitor of DNA binding (Id)
      proteins in the rat epididymis.
AB  - The epididymis is the site in which spermatozoa are matured and stored. Regional
      differences along the epididymis are essential for the establishment of the
      microenvironment required for germ cell maturation. Inhibitor of DNA binding (Id)
      proteins are transcription factors that modulate the functions of basic helix
      loop-helix (bHLH) transcription factors and act by binding to and sequestering
      bHLH proteins; the latter act to regulate cellular proliferation and
      differentiation. The objectives of this study were to determine the mRNA
      expression and the immunocytolocalization of Id1, Id2, Id3, and Id4 in the
      epididymis of adult rats and to determine the Id3 protein expression profile in
      orchidectomized and in aged animals. We found that, at the mRNA level, Id
      proteins are expressed in a unique, region-specific manner along the epididymis.
      Id1 immunoreactivity is specific to myoid cells; the presence of Id2 is observed
      in clear cells, myoid cells, and in the apical region of principal cells. Id3
      immunoreactivity is essentially confined to the nuclei of principal cells and
      myoid cells, whereas Id4 is observed mainly in myoid and narrow cells. Thus, Ids
      are localized to different cell types and are differentially expressed, at both
      the mRNA and protein levels, along the epididymis. Expression of Id3 is
      differentially regulated in response to orchidectomy along the epididymis. The
      fact that these regulators of gene expression are expressed in this manner may
      provide some insight into the differential expression of other genes that lead to
      region-specific differences along the epididymis, a hallmark of this tissue.

PMID- 16304208
TI  - Aging and the brown Norway rat leydig cell antioxidant defense system.
AB  - Previous studies have shown that testosterone production by the Leydig cells of
      aged Brown Norway rats is reduced from the relatively high levels produced by
      Leydig cells of young rats and that this reduction is not secondary to decreased
      serum luteinizing hormone concentration. The free radical theory of aging
      proposes that imbalance between pro-oxidants and the antioxidant defense system
      ultimately results in oxidative damage to cellular processes. With this in mind,
      we hypothesized herein that age-related reductions in steroidogenesis by Brown
      Norway rat Leydig cells may be associated with the impairment of the antioxidant
      defense system of these cells. To begin to test this hypothesis, we compared the
      activities and steady-state mRNA and protein levels of the antioxidant enzymes
      copper zinc (CuZn) superoxide dismutase (CuZnSOD, SOD1), manganese (Mn)
      superoxide dismutase (MnSOD, SOD2), and glutathione peroxidase (GPx) and the
      levels of reduced and oxidized glutathione in Leydig cells isolated from the
      testes of young (4-month-old) and aged (20-month-old) Brown Norway rats. For some
      studies, Leydig cells were isolated separately from aged testes that either had
      regressed because of age-related losses of germ cells or that were nonregressed.
      SOD (total) and GPx activities were found to decrease significantly with age
      whether or not the testes were regressed. CuZnSOD and MnSOD mRNA levels decreased
      with aging, though the magnitude of the decreases were considerably lower than
      the respective decreases in enzyme activities. GPx mRNA levels also decreased,
      which is consistent with the decreases seen in enzyme activity. MnSOD protein
      expression declined with age, and to a lesser extent, CuZnSOD did as well.
      Reduced and oxidized glutathione also exhibited age-related reductions in cells
      from both normal and regressed aged testes. The age-related decreases in Leydig
      cell antioxidant enzyme activities, gene expression, and protein levels and in
      glutathione were consistent with the hypothesis that the loss of steroidogenic
      function that accompanies Leydig cell aging may result in part from a decrease in
      the fidelity of the cellular antioxidant defense system.

PMID- 16304209
TI  - Erection- and ejaculation-preserving cystectomy with orthotopic urinary
      diversion: is it feasible?
AB  - Nerve-sparing techniques to preserve sexual function in men undergoing
      cystoprostatectomy have been documented by different centers. We evaluated the
      results of the first 4 erection- and ejaculation-preserving cystectomies
      performed in our department. The ages of patients ranged between 36 and 43 years.
      In all cases, patients wished to maintain sexual function. Of the cases, 3
      patients had pT1 G3 transitional cell carcinoma (TCC) refractory to treatment and
      one had pT2a adenocarcinoma of the bladder. Extirpation of the bladder and
      anterior proximal prostate en bloc with preservation of the vasa deferentia,
      seminal vesicles, posterior prostate, and neurovascular bundles was performed
      after pelvic lymphadenectomy. W-ileal neobladder was performed by using 40 cm of
      ileum. All patients had erections at the third month. Of the cases, 2 patients
      had antegrade ejaculation. The ejaculate volumes were 0.8 and 1.2 mL in patients
      with antegrade ejaculation. Patients in the other cases had retrograde
      ejaculation. All patients were continent day and night. We started clean
      intermittent catheterization in 1 case because of residual urine. There were no
      local recurrences. One patient with TCC died because of systemic disease in the
      postoperative 32nd month. The most important drawback of potent cases in
      cystectomy decision is erectile dysfunction after radical cystectomy. This
      drawback causes delay of the operation and sometimes mortality. As was the case
      in other reports, our limited number of cases in this study demonstrated that
      erection and ejaculation could be preserved in selected groups of patients.

PMID- 16304210
TI  - Recipient preparation and mixed germ cell isolation for spermatogonial stem cell
      transplantation in domestic cats.
AB  - The loss of genetic diversity poses a serious threat to the conservation of
      endangered species, including wild felids. We are attempting to develop
      spermatogonial stem cell transplantation in the cat as a tool to preserve and
      propagate male germ-plasm from genetically valuable animals, be they threatened
      wild species or lines of cats used as models for inherited diseases. In this
      study, we investigated the use of local external beam radiation treatment to
      deplete the endogenous germ cells of male domestic cats, a step necessary to
      prepare them for use as recipients for transplantation. Testes of 5-month-old
      domestic cats were irradiated with a fractionated dose of 3 Gy per fraction for 3
      consecutive days. These cats were castrated at 2, 4, 8, 16, and 32 weeks
      posttreatment, and progress of spermatogenesis was evaluated histologically and
      compared against age-matched controls. Even at the latest time points, less than
      10% of tubules contained germ cells at any stage of meiosis, showing the efficacy
      of this protocol. In addition, male germ cells were isolated from the testes of
      domestic cats using a 2-step enzymatic dissociation to establish a protocol for
      the preparation of donor cells. The presence and viability of spermatogonia
      within this population were demonstrated by successful transplantation into, and
      colonization of, mouse seminiferous tubules. The success of these protocols
      provides a foundation to perform spermatogonial stem cell transplantation in the
      domestic cat.

PMID- 16304211
TI  - Stromal fibrosis reaction in rat prostates induced by alpha 1 adrenergic
      stimulation.
AB  - Most of the publications dealing with the experimental induction of prostatic
      neoplasia have focused on the description of epithelial lesions, but little
      attention has been paid to the involvement of their stromal alterations. The
      present study is a first attempt to assess the stromal changes in both collagen
      and elastic fibrils as well as in its cellular constituents, which accompany
      prostatic intraepithelial neoplastic (PIN)-like lesions induced by phenylephrine
      (PE) in rats. Adolescent rats received subcutaneous injections of PE daily (10
      mg/kg/d) for 1 month. At the end of the experimental period the rats were
      sacrificed; the dissected ventral prostates were fixed in Stieve solution and
      paraffin-embedded; and sections were cut and stained accordingly. Most of the
      stromal cells were identified by immunohistochemistry techniques using primary
      antibodies to ED2 (resident macrophages), actin (fibrocytes and vascular smooth
      muscle cells), vimentin (mesenchymal cells), and 5'-bromo-2'-deoxyuridine (S
      phase proliferating cells). Collagen stromal mass was visualized by Gomori
      trichrome and individual collagen fibers by picrosirius red staining under
      polarized light, whereas the fine fibrils were stained according to the Pinkus
      method. The untreated rat prostates are characterized by a delicate interacinar
      stroma with scanty cells and fibrils. The PE-treated prostates showed a
      significant increase in both cellular and fibrillar elements as well as an
      increase in arteriolar density, in addition to the typical PIN lesions. The
      presence of such an interstitial fibrosis, which also includes inflammatory
      cells, neoangiogenesis, and synthesis de novo of collagen and fibers, might be
      regarded as a desmoplastic reaction. It is suggested that these changes could be
      related to a tissue repair process occurring subsequent to the inflammatory
      exudate that takes place during the incipient phases of the PE treatment.

PMID- 16304213
TI  - Setting up an open heart surgical program in a developing country.

PMID- 16304212
TI  - DNA damage in bovine sperm does not block fertilization and early embryonic
      development but induces apoptosis after the first cleavages.
AB  - The main goal of this study was to investigate whether and at what level damage
      of paternal DNA influences fertilization of oocytes and early embryonic
      development. We hypothesized that posttesticular sperm DNA damage will only
      marginally affect sperm physiology due to the lack of gene expression, but that
      it will affect embryo development at the stage that embryo genome (including the
      paternal damaged DNA) expression is initiated. To test this, we artificially
      induced sperm DNA damage by irradiation with x- or gamma rays (doses of 0-300
      Gy). Remarkably, sperm cells survived the irradiation quite well and, when
      compared with nonirradiated cells, sperm motility and integrity of plasma
      membrane, acrosome, and mitochondria were not altered by this irradiation
      treatment. In contrast, a highly significant logarithmic relation between
      irradiation dose and induced DNA damage to sperm cells was found by both terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) and
      the acridin orange assay. Despite the DNA damage, irradiated sperm cells did not
      show any sign of apoptosis (nuclear fragmentation, depolarization of inner
      mitochondrial membranes, or phospholipid scrambling) and were normally capable of
      fertilizing oocytes, as there was no reduction in cleavage rates when compared
      with nonirradiated sperm samples up to irradiation doses of less than 10 Gy.
      Further embryonic development was completely blocked as the blastocyst rates at
      days 7 and 9 dropped from 28% (nonirradiated sperm) to less than 3% by greater
      than 2.5-Gy-irradiated sperm. This block in embryonic development was accompanied
      with the initiation of apoptosis after the second or third cleavage. Specific
      signs of apoptosis, such as nuclear fragmentation and aberrations in spindle
      formation, were observed in all embryos resulting from in vitro fertilization
      with irradiated sperm (irradiation doses >1.25 Gy). The results show that sperm
      DNA damage does not impair fertilization of the oocyte or completion of the first
      2-3 cleavages, but blocks blastocyst formation by inducing apoptosis. Embryos
      produced by assisted reproductive techniques (ART) could have incorporated
      aberrant paternal DNA (frequently detected in sperm of sub/infertile males).
      Analogously, in the present work, we discuss the possibility of following embryo
      development of oocytes fertilized by ART through the blastocyst stage before
      embryo transfer into the uterus in order to reduce risks of reproductive failure.

PMID- 16304214
TI  - Comparison of antihypertensives after coronary artery surgery.
AB  - Hypertension following coronary artery bypass grafting is a common problem that
      may result in postoperative myocardial infraction or bleeding, Hemodynamic
      effects were compared in 45 hypertensive coronary bypass patients randomized to
      receive either diltiazem, nitroglycerin, or sodium nitroprusside. Diltiazem was
      administered as an intravenous bolus of 0.3 mg.kg-1 within 5 min, followed by
      infusion of 0.1-0.8 mg.kg-1.h-1 in group 1. Nitroglycerin was infused at a rate
      of 1-3 microg.kg.h-1 in group 2, and sodium nitroprusside was given at a rate of
      1-3 microg.kg-1.min-1 in group 3. Hemodynamic measurements were carried out
      before infusion (T1) and at 30 min (T2), 2 h (T3), and 12 h (T4) after initiation
      of treatment in the intensive care unit. Mean arterial pressure decreased
      significantly in all groups. There were no differences among groups at T1 and T2.
      At T3, heart rate in group 2 was significantly higher than group 1. At T3 and T4,
      the double product was highest in group 3 (group 1 vs. 3, p<0.001). These results
      suggest that the hemodynamic effects of the 3 drugs are similar within the first
      30 min. However, after 30 min, diltiazem affords better myocardial performance
      and more effective control of hypertension.

PMID- 16304215
TI  - Associated coronary anomalies in 135 Iranian patients with tetralogy of Fallot.
AB  - Coronary artery anomalies are common among patients with tetralogy of Fallot. One
      hundred and thirty-five patients (80 males and 55 females) with tetralogy of
      Fallot who underwent repair between 1995 and 2002 were studied to determine the
      incidence of coronary anomalies in Iranian patients. Eight (5.9%) patients (4
      males and 4 females) had a surgically relevant coronary artery anomaly: single
      coronary ostium in 5, origin of the left anterior descending artery from the
      right coronary artery in 2, and origin of the right coronary artery from the left
      coronary artery in 1. The surgical technique in 3 of these patients was repair of
      the ventricular septal defect with a transverse incision on the right ventricle,
      without damage to the coronary arteries. In another patient, an allograft aortic
      valve cylinder was inserted. In the other 4 patients with a single coronary
      ostium, placement of a limited transannular patch was adequate. Consideration of
      these anomalies during primary repair could decrease the risk of operation in
      such patients. However, it seems that the presence of anomalous coronary arteries
      does not affect incremental risk after surgical repair.

PMID- 16304216
TI  - Long-term pulmonary function after lobectomy for primary lung cancer.
AB  - The aim of this study was to investigate the factors affecting long-term
      postoperative pulmonary function with a view to increasing the application of
      combined resection, bronchoplasty, and induction therapy. Results in 80 patients
      who underwent lobectomy for primary lung cancer were analyzed. Predicted
      postoperative pulmonary function was calculated using the formula: postoperative
      predicted function=preoperative function x[1-(b-n)/(42-n)], where n and b are the
      numbers of obstructed segments and total segments, respectively, in the resected
      lobe. Spirometry was performed serially on the preoperative day, and at 3, 6, 12,
      18, and 24 months postoperatively. The difference between the predicted
      postoperative pulmonary function and the function measured at 12 months
      postoperatively was calculated, and clinical and therapeutic variables were
      analyzed. Univariate analysis revealed that the difference in vital capacity was
      significantly related to surgical approach, bronchoplasty, and induction therapy,
      while the difference in forced expiratory volume in one second (FEV1) correlated
      with surgical approach and induction therapy. Multiple regression analysis showed
      induction therapy to be the sole factor related to the differences in both vital
      capacity and FEV1. Lung resection after induction therapy may cause an additional
      loss of pulmonary function in the late phase.

PMID- 16304217
TI  - Nosocomial infections and balloon counterpulsation: risk factors and outcome.
AB  - Between February and September 2003, 136 (5.3%) of 2,558 patients undergoing
      cardiac surgery were supported with intra-aortic balloon counterpulsation. There
      were 71 infected (group 1) and 65 noninfected (group 2) patients. Risk factors
      for nosocomial infections were identified by univariate and multivariate
      analysis. On univariate analysis, significant risk factors were operation time,
      balloon pump duration, ventilation hours, duration of central venous catheter
      placement, amount of blood transfused, left ventricular ejection fraction<30%,
      intra- and/or postoperative intra-aortic balloon counterpulsation, surgery under
      cardiopulmonary bypass, combined procedures, re-exploration, and Acute Physiology
      And Chronic Health Evaluation (APACHE) II score. On multivariate analysis,
      ventilation hours and amount of blood transfused were independently associated
      with group 1. Respiratory tract infections were common in the balloon
      counterpulsation population (41.1%). Mortality was significantly higher in
      patients needing balloon pump support (19.9%) compared to controls (1.1%), but it
      was similar in groups 1 and 2. Recognition of risk factors for postoperative
      infection in patients undergoing cardiovascular surgical procedures with intra
      aortic balloon counterpulsation may help to improve their prognosis and allow
      more organized surveillance.

PMID- 16304218
TI  - Autologous pericardial valved conduit for the Ross operation.
AB  - The feasibility and function of autologous pericardial valved conduit for right
      ventricular outflow tract reconstruction in the Ross operation were assessed.
      Between June 1997 and April 2002, 31 patients underwent this procedure at our
      institution; one was lost to follow-up. The other 26 males and 4 females were
      aged 17 to 60 years (mean, 36.6 years). Causes of aortic valve disease were
      infective endocarditis in 26 and rheumatic valve disease in 4. Mean follow-up was
      16.7 months (range, 1-58 months). Preoperatively, 9 patients were in functional
      class II, 19 in class III, and 2 in class IV. Concomitant procedures included
      coronary artery bypass (1), mitral valve replacement (6), tricuspid valve
      replacement (1), and ventricular septal defect closure (1). Mean aortic
      crossclamp time was 199.4 min. There were 4 (13.3%) hospital deaths and no late
      death. Mean postoperative functional class was 1.17 with +0.36 aortic
      regurgitation, a peak gradient of 21.9 mm Hg (range, 6-59 mm Hg) across the
      conduit, and grade +0.96 pulmonary regurgitation. No conduit-related complication
      was detected. Use of autologous valved conduit for the Ross operation is
      feasible. Long-term follow-up is mandatory to assess durability.

PMID- 16304219
TI  - Intensive care unit readmission after elective coronary artery bypass grafting.
AB  - Prospective data of 3,120 consecutive patients who had elective coronary artery
      bypass were analyzed to identify patient profile, cost, outcome and predictors of
      those readmitted to the intensive care unit. Group A (n=3,002) had a single
      intensive care unit admission and group B (n=118) were readmitted within 30 days
      after surgery. Parsonnet score, EuroSCORE, age, body mass index, chronic
      obstructive airway disease, peripheral vascular disease, renal dysfunction,
      unstable angina, congestive cardiac failure, and poor left ventricular function
      were higher in group B. Bypass and crossclamp times were longer, and the
      prevalence of inotropic and balloon pump support, arrhythmias, myocardial
      infarction, re-exploration, blood loss and transfusion, cerebrovascular accident,
      wound infection, sternal dehiscence, and multisystem failure were higher in group
      B. Despite a 4-fold increase in cost of care, the mortality rate (32.4%) of
      patients readmitted to intensive care was 23-times higher than routine patients
      (1.4%). Crossclamp time>80 min, Parsonnet score>10, EuroSCORE>9, sternal
      dehiscence, ventricular arrhythmias, and renal failure predicted readmission.

PMID- 16304220
TI  - Surgery for non-small cell carcinoma in geriatric patients: 15-year experience.
AB  - The purpose of this study was to determine the clinical patterns, short- and long
      term survival in elderly patients after surgery for non-small cell lung
      carcinoma. The 273 patients aged over 70 years who underwent curative resection
      from 1986 to 2001 were retrospectively assessed. Mean age was 73.2+/-3.1 years,
      (11% were>80 years). The mean follow-up was 31 months. Standard procedures were
      used: 151 lobectomies, 49 bilateral lobectomies, 42 pneumonectomies, 9 sleeve
      resections, and 22 wedge resections. The 30-day mortality was 5.4%. Multivariate
      analysis showed that extended procedures, male sex, and age were predictors of
      mortality. Overall survival rates at 5, 10, and 15 years were 35.6%, 10.5%, and
      2.5%, respectively. Advanced disease stage, low forced expiratory volume in 1
      second, and previous cardiac disease were independent predictors that adversely
      influenced survival. Geriatric patients with non-small cell lung carcinoma can
      undergo resection safely with acceptable long-term survival. Lobectomy is the
      procedure of choice, extended resections should only be carried out in highly
      selected patients. Careful attention to preoperative clinical staging is
      important as the elderly beyond the early stage of disease fare poorly. Surgery
      is justified for the treatment of stage I-II lung cancer.

PMID- 16304221
TI  - Arch reconstruction without circulatory arrest in neonates.
AB  - Between May 2000 and December 2002, 10 neonates underwent arch reconstruction
      without circulatory arrest. Age at surgery ranged from 1 to 18 days, and body
      weight ranged from 1.62 to 3.38 kg. The diagnosis was interrupted aortic arch in
      4, hypoplastic left heart syndrome in 3, and coarctation complex in 3. A 3 mm
      polytetrafluoroethylene graft was anastomosed to the innominate artery, and the
      brain was perfused via this graft while the aortic arch was reconstructed.
      Regional cerebral oxygen saturation and the right and left radial artery
      pressures were monitored. There were 2 deaths: one because of low cardiac output
      syndrome after a Norwood operation; another from multiple organ failure due to
      preoperatively undetected congenital biliary atresia. Regional cerebral oxygen
      saturation was kept constant at over 40% during regional cerebral perfusion.
      There were no neurologic sequelae observed postoperatively. It was concluded that
      the regional cerebral perfusion technique can be safely applied during neonatal
      aortic arch reconstruction, and deep hypothermic circulatory arrest should be
      avoided.

PMID- 16304222
TI  - Low-dose anticoagulation in Chinese patients with mechanical heart valves.
AB  - The aim of this study was to provide guidelines for optimal anticoagulation in
      Chinese patients after mechanical heart valve replacement. A Carbomedics valve
      was implanted in 178 patients between July 2000 and July 2003. During follow-up,
      22 bleeding events and 1 thromboembolic complication occurred. The linearized
      rates of bleeding and thromboembolism were 5.83% and 0.26% per patient-year,
      respectively. The linearized mortality rate was 0.79% per patient-year. The final
      mean international normalized ratio (INR) was 1.68+/-0.38, however there was a
      significant variation between the early and late periods of follow-up. For
      Chinese patients with mechanical heart valves, bleeding was the major
      complication rather than thromboembolism. Low-dose anticoagulation (international
      normalized ratio 1.4-2.0) could markedly decrease bleeding and effectively
      prevent thromboembolism. As the INR was most unstable in the first postoperative
      month, re-examination of patients in this period is critical.

PMID- 16304223
TI  - Effect of prolonged intensive care stay on survival following coronary surgery.
AB  - The aim of the study was to examine midterm survival in patients who required
      prolonged recovery in the intensive care unit. The 5,186 consecutive patients who
      underwent isolated coronary surgery between April 1997 and March 2002 were
      retrospectively analyzed. Patients were classified as having prolonged (>3 days)
      or normal (<or=3 days) stay in the intensive care unit. Patient records were
      matched to the National Health Service Strategic Tracing Service which records
      all-cause mortality in the UK. Case-mix was controlled for by constructing a
      propensity score from core patient characteristics, which was included along with
      the comparison variable in a multivariable analysis of outcome. Prolonged
      intensive care unit stay was recorded in 475 (9.16%) patients. Mortality was
      9.14% during the study period with a total follow-up of 19,618 patient-years
      (mean, 3.8 years). Adjusted 5-year survival was 78.0% for prolonged intensive
      care unit stay vs. 90.7% for normal stay, with an adjusted hazard ratio for
      midterm mortality of 2.6 (p<0.001). Midterm mortality was significantly higher in
      patients with a prolonged intensive care unit stay following coronary bypass.

PMID- 16304224
TI  - Adaptive cardiac binding: a new method for treatment of dilated cardiomyopathy.
AB  - Adaptive cardiac binding, a new surgical procedure for advanced heart failure,
      allows a gradual increase in compression on the dilated heart, with separate
      loads on the left and right ventricles. A canine model of biventricular heart
      failure (anastomosis between the carotid artery and jugular vein and doxorubicin
      administration) was created. Twenty-four dogs were divided into 4 groups:
      control, adynamic cardiomyoplasty, plastic cardiac binding, and adaptive cardiac
      binding. In the adaptive cardiac binding group, fluid was added (35, 15, and 10
      mL) to each side of the pouch at weeks 1, 2, and 3. Left ventricular ejection
      fraction was 59%+/-4% before induction of heart failure and 27%+/-2% 6 weeks
      later. Immediately after the main operation, left ventricular ejection fractions
      were 35+/-3% (cardiomyoplasty), 34%+/-4% (plastic cardiac binding), and 35%+/-4%
      (adaptive cardiac binding). Four weeks later, left ventricular ejection fraction
      had not changed in the cardiomyoplasty (37%+/-3%) and plastic cardiac binding
      (32%+/-2%) groups, but significantly increased in the adaptive cardiac binding
      group (48%+/-5%); it had decreased to 23%+/-4% in controls. Adaptive cardiac
      binding is a promising new surgical approach for patients with end-stage heart
      failure.

PMID- 16304225
TI  - All internal thoracic artery composite graft revascularization.
AB  - The aim of this study was to determine the most efficient design of composite
      grafts and clarify the technical feasibility rate of composite grafting using
      internal thoracic artery exclusively in patients undergoing triple-vessel
      revascularization. Retrospective analysis of 104 consecutive patients was carried
      out. An in situ left internal thoracic artery graft for the left anterior
      descending artery area, with attachment of the right internal thoracic artery to
      the side of the left internal thoracic artery to revascularize the circumflex and
      right coronary vessels, was the most efficient graft design. The technical
      feasibility rate was 80% (83/104 patients). The mean number of distal anastomoses
      for the entire group was 3.8+/-0.8 per patient. Intraoperative left internal
      thoracic artery flow rate was 91.6+/-37.8 mL.min-1. With more experience, it is
      thought that the technical feasibility rate could be increased.

PMID- 16304226
TI  - Mid-term experience with valved bovine jugular vein conduits.
AB  - From June 1999 to January 2004, 43 children underwent implantation of a valved
      bovine jugular vein conduit and correction of complex congenital heart defects.
      Median age was 1.98 years (range, 11 days - 13.3 years). There were 7 early
      deaths (16.3%) unrelated to conduit failure or thrombosis. Median follow-up of 36
      survivors was 24 months (range, 1-48 months, quartile range, 12-48 months), total
      follow-up was 78 patient-years. There were 3 late deaths (8.3%) due to infection,
      pulmonary thromboembolism, and sudden cardiac arrest after re-operation to repair
      a right ventricular outflow tract aneurysm. There were 2 conduit explantations
      due to dysfunction and suspected endocarditis. Three patients underwent balloon
      dilatation of distal stenoses. The mean peak gradient through the pulmonary
      anastomosis was 15 mm Hg (range, 3-42 mm Hg) among patients free from re
      intervention. No severe valve regurgitation was observed. Freedom from re
      intervention was 72% at 48 months. This conduit remains a good alternative to
      homografts. Causes of distal stenosis must be clarified, guidelines for
      prophylactic anticoagulation must be created, and the role of percutaneous
      balloon dilatation established.

PMID- 16304227
TI  - Site-specific detection of bleeder using transesophageal echocardiography.
AB  - Transesophageal echocardiography continues to be an indispensable postoperative
      diagnostic tool for cardiac surgical patients. Transesophageal echocardiography
      was carried out postoperatively in 30 consecutive hypotensive patients with low
      cardiac output who had undergone coronary bypass surgery. In 19 of these
      patients, a cause of low cardiac output requiring surgical intervention was
      excluded, and they were managed conservatively. In 11 patients, a surgical cause
      of low cardiac output was indicated: diffuse bleeding from no particular site in
      5, and from a specific site in 6. They underwent urgent re-operation, and the
      echocardiography findings were confirmed on the operating table. Not only is
      transesophageal echocardiography important in diagnosis, but it is also highly
      specific in locating the site of bleeding.

PMID- 16304228
TI  - Traumatic giant pseudoaneurysm of innominate artery.
AB  - A 20-year-old man developed a giant pseudoaneurysm of the innominate artery 5
      months after blunt chest trauma, causing severe respiratory distress and superior
      vena cava compression symptoms. The patient was managed with hypothermia and low
      flow cardiopulmonary bypass resulting in a successful outcome.

PMID- 16304229
TI  - Endobronchial lipomatous hamartoma.
AB  - Pulmonary hamartomas are the most common benign neoplasm of the lung, occurring
      in the parenchyma or sometimes within the bronchi. Reported is a case of a 64
      year-old male patient with an endobronchial tumor. Sleeve left upper lobectomy
      was performed and histopathological examination revealed multiple growths of
      endobronchial hamartomatous foci. This report demonstrates that endobronchial
      hamartomas may develop from multiple foci.

PMID- 16304230
TI  - Secondary rupture of aorta following the surgical management of aortoesophageal
      fistula.
AB  - A patient suffering from an aortoesophageal fistula (AEF) caused by a fish bone,
      was treated in our institute in 2000. The operation was successful and the
      patient had an uneventful early postoperative course. However, the patient died
      of frank hematemesis on the 6th postoperative day due to secondary rupture of the
      aorta. The lessons learnt and surgical efforts to manage AEF caused by an
      esophageal foreign body are discussed.

PMID- 16304231
TI  - Coronary artery bypass surgery in a patient with a functional single lung.
AB  - Destroyed lung and pneumonectomy are associated with anatomic and physiologic
      changes that may interfere with the conduct of subsequent open heart surgery.
      Here we report a case of an autopneumonectomized patient who required open heart
      surgery. The preoperative, intraoperative and postoperative management of this
      patient was unique. Open heart procedures on patients with a single lung can be
      performed with acceptable operative mortality and morbidity.

PMID- 16304233
TI  - Saphenous vein patch plasty to correct saphenous graft and aortotomy mismatch.
AB  - Mismatch of aortotomy and saphenous vein graft size occasionally occurs and can
      compromise the contour of the anastomosis thereby jeopardising its patency. We
      describe an alternative technique of saphenous vein patch plasty to overcome this
      complication by giving a more desirable hooded contour to the anastomosis. This
      results in improved graft patency, hemostasis and clinical outcome.

PMID- 16304234
TI  - Modulation of systemic inflammatory response after cardiac surgery.
AB  - Cardiac surgery and cardiopulmonary bypass initiate a systemic inflammatory
      response largely determined by blood contact with foreign surfaces and the
      activation of complement. It is generally accepted that cardiopulmonary bypass
      initiates a whole-body inflammatory reaction. The magnitude of this inflammatory
      reaction varies, but the persistence of any degree of inflammation may be
      considered potentially harmful to the cardiac patient. 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
      cardiopulmonary bypass circuitry, and pharmacologic and immunomodulatory agents
      have been examined in clinical studies. This article briefly reviews the current
      concepts of the systemic inflammatory response following cardiac surgery, and the
      various therapeutic strategies being used to modulate this response.

PMID- 16304235
TI  - Cause or consequence: pannus formation on tissue aortic valve with extended life.

PMID- 16304236
TI  - Radiopathology and positive pressure ventilation in diaphragmatic hernia.

PMID- 16304237
TI  - Left bronchial isomerism.

PMID- 16304238
TI  - An unusual cause of syncope.

PMID- 16304239
TI  - Warfarin phobia.

PMID- 16304240
TI  - Suture failure causing paravalvular leak 20 years after mitral valve replacement.

PMID- 16304241
TI  - Historical perspective: a pathologic approach to the classification of idiopathic
      interstitial pneumonias.
AB  - The idiopathic interstitial pneumonias (IIPs) are a heterogeneous group of
      diffuse parenchymal diseases of unknown etiology. The pathologic classification
      of the IIPs has evolved considerably over the past 50 years and is based on the
      histopathologic pattern. A final, and clinically relevant, diagnosis often
      depends on integration of the histologic findings with the radiologic and
      clinical presentations. Specimens for histopathologic evaluation are best
      obtained by surgical wedge biopsy to allow the accurate recognition of the
      involvement patterns of these disorders. Two of the most common IIPs, idiopathic
      pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP), differ
      with respect to prognosis. Patients with IPF have a poorer prognosis than those
      with NSIP and most other IIPs. Within the NSIP diagnosis, a fibrotic pattern
      seems to be associated with a worse outcome than a cellular pattern. By
      distinguishing IPF from other clinicopathologic entities, clinicians should be
      better able to identify optimal treatment strategies and hopefully to improve
      patient outcomes.

PMID- 16304242
TI  - Diagnosis: to biopsy or not to biopsy: assessing the role of surgical lung biopsy
      in the diagnosis of idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic disorder that is associated with
      a poorer prognosis than subacute idiopathic interstitial pneumonias (IIPs). IPF
      can be differentiated from other IIPs on the basis of its histologic pattern of
      usual interstitial pneumonia (UIP). Although a surgical lung biopsy specimen
      showing a UIP pattern is required for the definitive diagnosis of IPF, clinical
      criteria can be used in the absence of a lung biopsy specimen to make a likely
      diagnosis of IPF. The predictive value of these criteria largely depends on the
      expertise of the clinician and radiologist, but considerable interobserver
      variability exists even when evaluations are performed by experts in the field.
      Moreover, these criteria lead to misdiagnosis in about 25 to 35% of cases.
      Interobserver variability is reduced and diagnostic accuracy is improved in cases
      in which a diagnosis is made with a high degree of confidence. Diagnostic
      accuracy is also higher when the diagnosis is made by a core group of experts
      rather than by a referring center. The decision on whether or not to perform a
      surgical lung biopsy is difficult. It is clearly indicated in cases in which
      clinical or radiologic findings are atypical or when the diagnosis is made with a
      low degree of certainty.

PMID- 16304243
TI  - Pathogenesis and natural history of usual interstitial pneumonia: the whole story
      or the last chapter of a long novel.
AB  - Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) is not
      well-understood. Current explanations of the natural history and pathogenesis of
      IPF/UIP are controversial, and ongoing research continues to investigate multiple
      hypotheses. A complete understanding of the natural history of IPF could
      potentially help to identify different mechanisms that are operative at the
      early, intermediate, and end stages of the disease. This knowledge could lead to
      the development of more effective therapeutic interventions that target stage
      specific aberrant pathways involved in IPF/UIP pathogenesis.

PMID- 16304244
TI  - Therapeutic intervention: assessing the role of the international consensus
      guidelines.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disorder of
      unknown etiology. The consensus statement released by the American Thoracic
      Society and European Respiratory Society has provided guidelines for the
      diagnosis, evaluation, and management of patients with IPF. These guidelines
      suggest the use of conventional treatment options including therapy with
      corticosteroids and immunosuppressive agents. The guidelines statement
      acknowledged the fact that there is little good-quality evidence to support the
      safety and efficacy of such therapies in patients with IPF. The statement was
      published in 2000 and was based on an extensive review of the literature up to
      and including December 1998. The goal of this review is to reexamine the
      treatment recommendations of the guidelines statement in the context of data that
      has since become available.

PMID- 16304245
TI  - Case study review.
AB  - Examining case studies from patients with interstitial lung diseases (ILDs) is
      important in order to evaluate current diagnosis and treatment options. Two cases
      will be discussed; the first case examines a patient with usual interstitial
      pneumonia, and the second case examines a patient with subacute ILD and elements
      to suggest a forme fruste presentation of an unclassifiable connective tissue
      disease. Each case highlights components of the differential diagnosis, as well
      as reviews the treatments and prognoses of these patients. The cases provide
      clinical pearls that are designed to enhance the reader's understanding of ILDs.

PMID- 16304246
TI  - Therapeutic value of a lung protective ventilation strategy in acute lung injury.

PMID- 16304247
TI  - What's in a day?

PMID- 16304248
TI  - Becoming a complete "asthmologist".

PMID- 16304249
TI  - High tidal volume and positive fluid balance are associated with worse outcome in
      acute lung injury.
AB  - STUDY OBJECTIVES: Recent data have suggested that ventilatory strategy could
      influence outcomes from acute lung injury (ALI) and ARDS. We tested the
      hypothesis that infection/sepsis and use of higher tidal volumes than those
      applied in the ARDS Network (ARDSnet) study (> 7.4 mL/kg of predicted body
      weight) would worsen outcome in patients with ALI/ARDS. DESIGN: International
      cohort, observational study. SETTING: One hundred ninety-eight European ICUs
      participating in the Sepsis Occurrence in Acutely Ill Patients study. PATIENTS OR
      PARTICIPANTS: All 3,147 adult patients admitted to one of the participating ICUs
      between May 1, 2002, and May 15, 2002. INTERVENTIONS: None. MEASUREMENTS AND
      RESULTS: Patients were followed up until death, hospital discharge, or for 60
      days. Of the 3,147 patients, 393 patients (12.5%) had ALI/ARDS. ICU and hospital
      mortality was higher in patients with ALI/ARDS than those without ALI/ARDS (38.9%
      vs 15.6% and 45.5% vs 21.0%, respectively; p < 0.001). A multivariable logistic
      regression analysis with ICU outcome as the dependent factor showed that the
      independent risks for mortality were as follows: presence of cancer, use of tidal
      volumes higher than those used by the ARDSnet study, degree of multiorgan
      dysfunction, and higher mean fluid balance. Sepsis, septic shock, and oxygenation
      at the onset of ALI/ARDS were not independently associated with higher mortality
      rates. CONCLUSIONS: In addition to comorbidities and organ dysfunction, high
      tidal volumes and positive fluid balance are associated with a worse outcome from
      ALI/ARDS.

PMID- 16304250
TI  - Admission hyperglycemia and other risk factors as predictors of hospital
      mortality in a medical ICU population.
AB  - BACKGROUND: Tight glycemic control is recommended for patients in the ICU, as
      hyperglycemia is associated with increased morbidity and mortality. DESIGN:
      Observational cohort of patients admitted to a 12-bed, inner-city, medical ICU
      (MICU). SUBJECTS: A total of 1,185 of 1,506 patients from July 1, 1999, to
      December 31, 2002, selected based on a diagnosis other than diabetic ketoacidosis
      or glycemia > 280 mg/dL or < 80 mg/dL. PURPOSES: To determine if the highest
      serum glucose level within 24 h after ICU admission is associated with increased
      hospital mortality when adjusted for confounders. MEASUREMENTS: Age, gender,
      race, worst values within 24 h after ICU admission to construct the acute
      physiology and chronic health evaluation (APACHE) II score, and highest glucose
      within 24 h after ICU admission. Hospital mortality was the primary outcome.
      Admitting diagnosis, MICU length of stay (LOS), and hospital LOS were obtained.
      Glucose, albumin (n = 867), and lactic acid (n = 319) were stratified for
      analysis. ANALYSIS: Univariate analysis identified factors included in the
      multivariate model. RESULTS: Patients were predominantly African-American (79%)
      and men (56%; mean age, 49.2 years). The mean ICU admission highest glucose level
      was 139 +/- 43.7 mg/dL (+/- SD). MICU LOS and hospital LOS were 6.2 days and 12.9
      days, respectively, and 50% of patients received mechanical ventilation. MICU and
      hospital mortality were 18% and 20%, respectively; standardized mortality ratio
      was 66%. On univariate analysis, survivors (n = 945) and nonsurvivors (n = 240)
      showed APACHE II score, mechanical ventilation, hypoalbuminemia, lactic acidemia,
      and logistic organ dysfunction system score to be hospital mortality predictors;
      however, the highest admission serum glucose level was not. Logistic regression
      estimated APACHE II score/per point (odds ratio, 1.06; 95% confidence interval,
      1.02 to 1.11), mechanical ventilation (odds ratio, 3.06; 95% confidence interval,
      1.34 to 6.96), severe hypoalbuminemia (< 2 g/dL) [odds ratio, 2.98; 95%
      confidence interval, 1.3 to 7.02], and severe lactic acidemia (> or = 8 mmol/L)
      [odds ratio, 7.3; 95% confidence interval, 2.14 to 24.9], but not ICU admission
      hyperglycemia, to be associated with hospital mortality. CONCLUSIONS:
      Conventional factors of disease severity, but not highest glucose value during
      the first 24 h after ICU admission, predict hospital mortality in an inner-city
      MICU.

PMID- 16304251
TI  - Determinants of time-to-weaning in a specialized respiratory care unit.
AB  - BACKGROUND: As the decision-making process in long-term respiratory care units
      often depends on time-based outcomes, we sought to identify independent
      predictors of time-to-weaning (TTW) in a hospital-based specialized respiratory
      care unit. METHODS: Characteristics that were identified in previous studies as
      predictors of weaning success in ICUs and long-term ventilator units were
      prospectively collected on 113 consecutive admissions to our unit. TTW analyses
      were performed with Kaplan-Meier curves, log rank test, and Cox proportional
      regression. RESULTS: The TTW was shorter in patients with static lung compliance
      (Cst) of > 20 mL/cm H(2)O, a normal creatinine level (0.6 to 1.4 mg/dL), a rapid
      shallow breathing index (RSBI) of < or = 105, intact skin, and in those patients
      from a surgical referral source. We found an interaction between RSBI and Cst (p
      = 0.02) such that patients with an RSBI of < or = 105, regardless of Cst, had a
      median TTW of 11 days, those with an RSBI of > 105 and a Cst of > 20 had a median
      TTW of 31 days, and those with an RSBI of > 105 and a Cst of < or = 20 mL/cm
      H(2)O had not reached a median TTW by 60 days (p = 0.007 [log rank for linear
      trend]). In a Cox-proportional hazard model, both this categorization model of
      RSBI and Cst, and renal function had a significant impact on TTW. CONCLUSIONS: In
      a multivariate model incorporating the variables reviewed, only the lung
      parameters (RSBI combined with Cst) and renal function remained independently
      associated with TTW.

PMID- 16304252
TI  - Comparison of plasma eotaxin family level in aspirin-induced and aspirin-tolerant
      asthma patients.
AB  - STUDY OBJECTIVE: Eosinophilic infiltration of airway tissue is a central feature
      of aspirin-induced asthma (AIA). Eotaxins belong to the family of CC chemokines,
      which coordinate the recruitment of inflammatory cells bearing chemokine (C-C
      motif) receptor-3 to sites of allergic inflammation. In the present study, the
      levels of eotaxin-1, eotaxin-2, and eotaxin-3 following an oral aspirin
      provocation test (APT) were measured, and the relationship between the eotaxin
      level and clinical parameters in patients with asthma was evaluated. PATIENTS AND
      DESIGN: An APT was performed in patients with asthma. Twenty AIA patients and 23
      aspirin-tolerant asthma (ATA) patients were identified. Plasma levels of eotaxin
      1, eotaxin-2, and eotaxin-3 levels were measured by enzyme-linked immunosorbent
      assay in the 43 patients with asthma and in 39 control subjects. RESULTS: The
      proportion of blood eosinophils was significantly higher in asthmatic patients
      than in control subjects. Nasal polyps were more common in AIA patients than in
      ATA patients (p < 0.05). In addition, the eotaxin-1 level was higher in AIA and
      ATA patients than in control subjects (p < 0.01 for each). The eotaxin-2 level
      was higher in ATA patients than in either the AIA patients (p < 0.05) or control
      subjects (p < 0.01). Similarly, the eotaxin-3 level was higher in ATA patients
      than in control subjects. A trend toward higher plasma levels of eotaxin-1 and
      eotaxin-3 at baseline and at 4 h after APT administration in the ATA group was
      noted but was not significant. Eotaxin-2 was also higher in ATA patients than in
      AIA patients at baseline and at 4 h after the APT. CONCLUSION: This study shows
      that eotaxin-2 is differentially secreted in patients with asthma according to
      aspirin intolerance, and that secretion is not time-dependent in response to the
      APT in AIA and ATA patients. It therefore appears that eotaxin-2 may be up
      regulated and may act differentially in patients with ATA.

PMID- 16304253
TI  - Understanding participation in an asthma self-management program.
AB  - STUDY OBJECTIVE: Asthma education programs improve asthma treatment results
      significantly. Low participation rate is a recurrent problem that impedes the
      efficiency of those programs. The purpose of this study was to investigate social
      cognitive determinants of the intention to participate in an asthma self
      management program. DESIGN: Structured interview. SETTING: Outpatient clinic,
      University Hospital Gasthuisberg, Leuven, Belgium. PATIENTS: One hundred seven
      asthmatic outpatients (mean age 42 years; 35% male). INTERVENTIONS: Patients
      received a standard explanation about the asthma program, were invited to
      participate, and were questioned about their beliefs about the program offered.
      MEASUREMENTS AND RESULTS: A social cognitive framework (attitude, social
      influence, and self-efficacy model) was used to compose a structured interview
      that was administered to assess the patients' attitude toward the program
      (perceived benefits), their social influence, and self-efficacy expectations to
      participate (perceived barriers). Asthma-related health behavior and clinical and
      demographic characteristics were evaluated by means of questionnaires. Fifty-nine
      percent of the patients expressed the intention to participate. Logistic
      regression analysis resulted in a model explaining 72% of the variance of
      intentions (Nagelkerke R(2) = 0.72). Having few structural barriers to
      participate was a significant predictor of participation (odds ratio [OR], 12.5;
      95% confidence interval, 5.2 to 19.3), next to believing in the personal benefits
      of the program (OR, 7.6; 95% confidence interval, 2.4 to 12.5), social influence
      (OR, 3.3; 95% confidence interval, 1.3 to 8.4), and education level (OR, 2.7; 95%
      confidence interval, 1.3 to 5.6). CONCLUSIONS: Recruitment of patients with
      asthma for an educational program should emphasize personal benefits of the
      program, should include patients' social network, and should consider the impact
      of structural barriers on participation behavior.

PMID- 16304254
TI  - Effect of treating allergic rhinitis with corticosteroids in patients with mild
      to-moderate persistent asthma.
AB  - STUDY OBJECTIVES: Rhinitis and asthma are considered to be synchronic or
      sequential forms of the same allergic syndrome. Treating the inflammation
      associated with allergic rhinitis influences the control of asthma. However, few
      studies have investigated the effect of treating perennial rhinitis on persistent
      asthma and vice versa. We determined the effects of inhaled or topical nasal
      beclomethasone dipropionate (BDP) administered separately or in combination on
      the control of asthma and bronchial hyperresponsiveness (BHR) in patients with
      the rhinitis/asthma association. DESIGN: A double-blind, parallel, three-group
      study. SETTING: Outpatient clinic of Pulmonary Division/Heart Institute (InCor)
      and the Division of General Internal Medicine, University of Sao Paulo Medical
      School, Sao Paulo, Brazil. PATIENTS: Seventy-four patients with mild-to-moderate
      asthma and allergic rhinitis (median age, 25 years). INTERVENTIONS: Patients
      received nasal or inhaled BDP separately or in combination for 16 weeks after a 2
      week placebo run-in period. MEASUREMENTS AND RESULTS: Nasal and pulmonary
      symptoms, as well as pulmonary function and BHR, were compared among the three
      groups after 4 weeks and 16 weeks of treatment. Patients in all three groups
      demonstrated a progressive and significant decrease in nasal and pulmonary
      symptoms, which started after 4 weeks (p < 0.05) and continued through the end of
      treatment (p < 0.001). Clinical improvement was similar and parallel in the three
      groups. Asthma-related morbidity, evaluated by quantifying absence from work,
      emergency department visits, and nighttime awakenings, also decreased in the
      three groups (p < 0.05). CONCLUSIONS: Failure to consider treatment of rhinitis
      as essential to asthma management might impair clinical control of asthma.
      Furthermore, these data suggest that asthma and rhinitis in some patients can be
      controlled by the exclusive use of nasal medication.

PMID- 16304255
TI  - Interferon-gamma up-regulates expression of cysteinyl leukotriene type 2
      receptors on eosinophils in asthmatic patients.
AB  - STUDY OBJECTIVES: Cysteinyl leukotrienes (cysLTs) are strong bronchoconstrictive
      mediators that play a key role in asthma inflammation. They act through specific
      receptors including cysLT type 1 receptor (CysLT1R) and cysLT type 2 receptor
      (CysLT2R). Although these two receptors are co-expressed on inflammatory cells,
      little is known about CysLT2R in patients with asthma. The aims of this study
      were to investigate the changes in cysLT receptors (CysLTRs) during asthma
      exacerbations and to determine which cytokine modulates CysLTR expression on
      eosinophils. METHODS: We assessed protein expression and messenger RNA of CysLT1R
      and CysLT2R in peripheral blood eosinophils and measured urinary leukotriene E(4)
      levels in 36 patients with stable asthma, 23 subjects with asthma exacerbation,
      and 15 healthy subjects. We also evaluated the modulation of these receptors by
      interleukin (IL)-1beta, IL-4, IL-5, IL-13, interferon (IFN)-gamma and tumor
      necrosis factor-alpha in cultured eosinophils. RESULTS: Expression of both
      CysLT1R and CysLT2R on eosinophils during asthma exacerbations was significantly
      higher (p < 0.05) than in stable asthma and healthy subjects. A greater
      expression of CysLT2R in exacerbation was found in nonatopic asthmatics. Only IFN
      gamma up-regulated cell-surface expression of CysLT2R in a dose-dependent manner
      and enhanced messenger RNA levels. No cytokine affected CysLT1R expression or
      messenger RNA level. CONCLUSIONS: CysLT2R expression on eosinophils was increased
      in patients, especially in nonatopic subjects, during asthma exacerbation, and
      was up-regulated by IFN-gamma; therefore we speculate that a pathway through
      CysLT2R might modulate exacerbations of asthma.

PMID- 16304256
TI  - Mortality from acute pulmonary embolism according to season.
AB  - BACKGROUND: Varying observations have been made on seasonal differences of
      mortality from acute pulmonary embolism (PE). METHODS: The number of deaths each
      year from PE, from 1980 through 1998, based on death certificates, was obtained
      from the US National Center for Health Statistics Multiple Cause-of-Death Files.
      RESULTS: Acute PE as the cause of death ranged from 0.91 to 1.03 PE deaths per
      quarter per 100,000 population. Small differences were statistically significant
      due to the large number of patients evaluated. Quarterly mortality rates from PE
      in the northeast, south, midwest, and west, where seasonal weather varies widely,
      showed no meaningful seasonal differences. CONCLUSION: Mortality rates from PE do
      not vary to a meaningful extent according to season.

PMID- 16304257
TI  - Use of exhaled breath condensate in the study of airway inflammation after
      hypertonic saline solution challenge.
AB  - STUDY OBJECTIVES: Hypertonic saline solution inhalation is suspected to produce
      airway inflammation. DESIGN: The aim of this study was to verify this hypothesis
      by measuring inflammatory markers in exhaled breath condensate (EBC) collected
      before and after sputum induction with hypertonic and isotonic saline solution.
      PATIENTS AND METHODS: We enrolled 10 patients with asthma, 10 patients with COPD,
      and 7 healthy subjects with no history of lung disease. Levels of interleukin
      (IL)-6 and tumor necrosis factor (TNF)-alpha were measured in EBC by a specific
      enzyme immunoassay kit. Exhaled pH was measured after deaeration/decarbonation by
      bubbling with argon (350 mL/min) for 10 min by means of a pH meter. MEASUREMENTS
      AND RESULTS: Exhaled IL-6 and TNF-alpha concentrations were greater and pH was
      decreased compared to baseline after hypertonic saline solution inhalation in
      each group of subjects studied. No changes were observed following isotonic
      saline solution inhalation. Concentrations of IL-6, TNF-alpha, and pH in EBC
      correlated. CONCLUSIONS: These findings suggest that hypertonic saline solution
      inhalation could cause a low-grade inflammation in airways, and levels of
      inflammatory markers such as IL-6, TNF-alpha, and pH in EBC may be a useful
      noninvasive way to assess and monitor airway inflammation.

PMID- 16304258
TI  - Antiprotease function of airway secretions in purulent tracheobronchitis.
AB  - STUDY OBJECTIVES: Unopposed activity of the serine protease, human leukocyte
      elastase (HLE), is detectable in the airways of patients with purulent
      tracheobronchitis. The aim of this study was to assess the compartmentalization
      of HLE activity in the liquid sol phase and the solid gel phase of airway
      secretions. DESIGN: Seventy samples of tracheobrochial aspirates were obtained
      from patients who had hypersecretion and were receiving mechanical ventilation.
      METHODS: Samples were separated into sol and gel ("mucous pellet") phases, and
      HLE activity was measured using chromogenic substrate degradation. HLE was eluted
      from the mucous pellet using hypertonic saline solution, 1 mol/L, or bovine
      pancreatic deoxyribonuclease (DNase), 16 micromol/L. RESULTS: HLE activity
      partitioned between the sol and gel phases of the secretions, with most of the
      activity present in the gel phase (32:1 ratio of gel to sol HLE activity). The
      activity of HLE was 95% inhibited when bound to the gel phase, but activity
      appeared to be largely restored after elution from the gel phase. The gel phase
      was capable of binding additional exogenous HLE, and its binding capacity for
      exogenous HLE was not saturated by concentrations that exceeded the highest
      clinically relevant HLE levels (1.1 mg/mL). Hypertonic saline solution and DNase
      I efficiently liberated endogenous and exogenous gel phase-bound HLE activity,
      suggesting that electrostatic bonds and DNA, respectively, play important roles
      in binding HLE to the gel phase. CONCLUSIONS: The solid phase of airway
      secretions is a more important modulator of elastase-antielastase balance than
      has been previously recognized.

PMID- 16304259
TI  - The effects of 1 year of specific inspiratory muscle training in patients with
      COPD.
AB  - AIM: We assessed the long-term benefits of inspiratory muscle training (IMT) on
      inspiratory muscle strength, exercise capacity, the perception of dyspnea,
      quality of life, primary care use, and hospitalizations in patients with
      significant COPD. PATIENTS: Forty-two consecutive COPD patients with FEV(1) < 50%
      of predicted were randomized into a group that received IMT for 1 year, and a
      control group that received training with a very low load. RESULTS: There was a
      statistically significant increase in inspiratory muscle strength (at the end of
      the third month of training) as assessed by maximal inspiratory pressure (from 71
      +/- 4.9 to 90 +/- 5.1 cm H(2)O [+/- SEM], p < 0.005) and 6-min walk distance (at
      the end of the third month of training; from 256 +/- 41 to 312 +/- 54 m; p <
      0.005), a decrease in the mean Borg score during breathing against resistance (at
      the end of the ninth month of training), improvement in the health-related
      quality-of-life scores (at the end of the sixth month of training) in the
      training group but not in the control group. At the end of the training year,
      these changes were maintained; in addition, a decrease in primary health-care use
      and hospitalization days was observed. CONCLUSIONS: Our study shows that during
      IMT in patients with significant COPD, there is an increase in exercise capacity,
      improvement in quality of life, and decrease in dyspnea. Our study also provides
      evidence that long-term IMT can decrease the use of health services and
      hospitalization days.

PMID- 16304260
TI  - Low-grade systemic inflammation and the response to exercise training in patients
      with advanced COPD.
AB  - STUDY OBJECTIVE: Low-grade systemic inflammation may cause a chronic catabolic
      state that may affect trainability in patients with COPD as has been seen
      previously in healthy elderly. Therefore, the aim of the present study was to
      study the relationship between baseline circulating levels of inflammatory
      markers and the response to exercise training in clinically stable patients with
      COPD. DESIGN: An open prospective intervention study. SETTING: Tertiary care
      setting, University Hospital Gasthuisberg, Leuven, Belgium. PATIENTS: Seventy
      eight clinically stable outpatients with COPD. INTERVENTION: A 12-week outpatient
      exercise-training program consisting of strengthening and endurance types of
      exercises. MEASUREMENTS AND RESULTS: Circulating levels of inflammatory markers
      were assessed at baseline. Moreover, lung function, quadriceps force (QF), peak
      and functional exercise capacity, and health-related quality of life were
      determined at baseline and after the intervention. Sixty-five of the 78
      consecutive outpatients completed the study protocol. QF, peak and functional
      exercise capacity and health-related quality of life improved significantly
      compared to baseline. The absolute changes in health-related quality of life
      showed weak relationships with baseline circulating levels of interleukin-8
      (CXCL8) in the whole group (n = 65; r= -0.26; p = 0.04). In addition, soluble
      tumor necrosis factor receptor p55 was strongly and positively related to the
      absolute changes in QF in the female patients only (n = 18; r = 0.81; p =
      0.0001), while CXCL8 was inversely related to the absolute change in the total
      score of the Chronic Respiratory Disease Questionnaire (r= -0.65; p = 0.004).
      CONCLUSION: Baseline markers of low-grade systemic inflammation did not clearly
      explain the variances in absolute changes in QF, the distance walked in 6 min,
      peak external load, or health-related quality of life following a 12-week
      exercise-training program. Hence, they seem not very constructive in the
      characterization of patients with advanced COPD who do or do not respond to
      exercise training.

PMID- 16304261
TI  - Elevated oxidative stress and reciprocal reduction of vascular endothelial growth
      factor levels with severity of COPD.
AB  - STUDY OBJECTIVES: The prevalent theory concerning the pathogenesis of COPD is
      that it is an imbalance between oxidants and antioxidants. However, it has been
      reported that a decrease in vascular endothelial growth factor (VEGF) might
      affect the pathogenesis of COPD. Therefore, this study was designed to examine
      the differences between oxidative stress and VEGF levels, and the severity of
      COPD. DESIGN: Controlled cross-sectional analysis. SETTING: University hospital.
      PARTICIPANTS: Twelve healthy control subjects and 57 COPD patients were included
      in this study. These COPD patients were divided into four groups based on the
      Global Initiative for Chronic Obstructive Lung Disease classification (mild COPD,
      14 patients; moderate COPD, 15 patients; severe COPD, 16 patients; very severe
      COPD, 12 patients). MEASUREMENTS AND RESULTS: Inflammatory markers, degree of
      oxidative stress, and VEGF levels were examined in sputum samples from all
      subjects. Nitrogen oxide levels in induced sputum were significantly higher in
      COPD patients than in healthy control subjects, and they increased with increases
      in the severity of COPD. In contrast, peroxynitrite inhibitory activity decreased
      with increases in the severity of COPD. Therefore, the mean (SD) peroxynitrite
      stress (ie, the nitrogen oxide level/peroxynitrite inhibitory activity ratio)
      steeply increased with increases in the severity of COPD (mild COPD: 8.4; SD,
      1.5; p = 0.02; moderate COPD: 10.8; SD, 1.4; p < 0.0001; severe COPD: 14.5; SD,
      2.5; p < 0.0001; very severe COPD: 18.3; SD, 4.1; p < 0.0001) compared with that
      of healthy control subjects. VEGF levels in induced sputum reciprocally decreased
      with severity of COPD (mild COPD: 1,360 pg/mL; SD, 800 pg/mL; p = 0.97; moderate
      COPD: 1,180 pg/mL; SD, 760 pg/mL; p = 0.50; severe COPD: 650 pg/mL; SD, 450
      pg/mL; p = 0.007; very severe COPD: 480 pg/mL, SD, 240 pg/mL; p = 0.002). In
      addition, peroxynitrite inhibitory activity in COPD patients exhibited an
      accelerated decline from the mean VEGF level in healthy control subjects.
      CONCLUSIONS: Elevated oxidative stress levels and a reciprocal reduction of VEGF
      levels in induced sputum were prominent with increases in the severity of COPD.
      Thus, epithelial cell injury mediated by oxidative stress may induce the decrease
      in lung VEGF levels, resulting in the promotion of the development of COPD.

PMID- 16304262
TI  - Factors associated with medication nonadherence in patients with COPD.
AB  - STUDY OBJECTIVES: To identify the predictors of medication adherence in patients
      with COPD and contrast the health beliefs, experiences, and behaviors of COPD
      patients self-reporting good adherence with those of patients reporting
      suboptimal adherence to their medications. DESIGN: Cross-sectional self
      administered questionnaire. SETTING: Ambulatory care. PARTICIPANTS: Patients with
      chronic respiratory ailments identified through respiratory support groups and
      from a pulmonary rehabilitation database. MEASUREMENTS AND RESULTS: A 30-item
      questionnaire comprising items pertaining to health beliefs, experiences, and
      behaviors along with a valid self-reported measure of adherence-the medication
      adherence report scale (MARS)-was administered to 525 ambulatory patients with
      chronic lung conditions. A total of 276 usable responses were received (52.6%).
      The mean age of the respondents was 71 years, and there were slightly more male
      patients (54.4%). COPD was the underlying disease condition in 90.6% of the
      respondents; two thirds of the respondents had comorbid conditions. The
      respiratory condition was managed by both general practitioners and respiratory
      specialists in 61.2% of cases. One third of the respondents self-reported
      complementary and alternative medicine use. The mean score (+/- SD) on the MARS
      among the respondents was 23.37 +/- 2.09. One hundred two patients self-reported
      perfect adherence on the MARS. Differences in knowledge about the illness and
      treatment, faith in and satisfaction with the treatment and doctors, concerns
      about the treatment, and intentional and unintentional deviations from the
      recommended treatment were detected between the adherent and less adherent
      groups. In multivariate analysis, "I vary my recommended management based on how
      I am feeling" and "I get confused about my medications" were found to be
      significant independent predictors of nonadherence. CONCLUSIONS: Patients'
      acceptance of the disease process and recommended treatment, knowledge about and
      faith in the treatment, effective patient-clinician interaction, and
      routinization of drug therapy are critical for optimal medication adherence in
      patients with COPD.

PMID- 16304263
TI  - Endogenous hydrogen sulfide in patients with COPD.
AB  - OBJECTIVES: COPD is characterized by progressive airway obstruction. Recent
      studies showed that besides nitric oxide (NO) and carbon monoxide (CO),
      endogenous hydrogen sulfide (H(2)S) might be the third signaling gasotransmitter.
      To clarify the role of endogenous H(2)S in the pathogenesis of COPD, we
      investigated the relation of serum H(2)S level to severity of COPD as defined by
      lung function and airway inflammation. METHODS: Levels of serum H(2)S and NO,
      lung function, and cell differential counts in induced sputum were studied in 27
      patients with acute exacerbation of COPD (AECOPD), 37 patients with stable COPD,
      and 13 healthy subjects. Patients with AECOPD had arterial blood gas levels
      measured and underwent Doppler echocardiography. In addition, in order to clarify
      the effects of age and smoking status on serum H(2)S level, we recruited three
      groups who were age matched to the study group but had no airflow limitation (59
      subjects). RESULTS: Serum H(2)S level (34.0 +/- 0.9 to 36.4 +/- 1.1 micromol/L
      [+/- SEM]) did not differ among healthy control subjects with different ages
      (56.6 to 75.0 years, respectively). Serum H(2)S level was significantly higher in
      patients with stable COPD than in patients with AECOPD and age-matched control
      subjects (p < 0.01) and correlated positively with NO level in all healthy
      control subjects and all patients with COPD (r = 0.352, p = 0.000). Serum H(2)S
      level was significantly lower in smokers than nonsmokers, both with AECOPD (p <
      0.05) and healthy control subjects (p < 0.01). It was significantly lower in
      smokers with AECOPD than healthy smokers and smokers with stable COPD (p < 0.01).
      Serum H(2)S level differed and was decreased (p < 0.05) among stable COPD
      patients by stage of airway obstruction (p < 0.05), and it was lower in patients
      with stage III than stage I obstruction (p < 0.05). Serum H(2)S level in all
      patients with COPD and healthy control subjects correlated positively with the
      percentage of predicted FEV(1) value (r = 0.300, p = 0.009). It was lower in
      patients with AECOPD and systolic pulmonary artery pressure (PASP) > or = 35 mm
      Hg than those with PASP within the normal range (< 35 mm Hg) [p < 0.05] and was
      negatively correlated with PASP (r = - 0.561, p = 0.011). Serum H(2)S level was
      negatively correlated with proportion of neutrophils in sputum (r = - 0.422, p =
      0.001) and positively correlated with proportion of lymphocytes (r = 0.286, p =
      0.028) and macrophages (r = 0.334, p = 0.01) in all patients with COPD.
      CONCLUSIONS: Endogenous H(2)S is involved in the pathogenesis of airway
      obstruction in COPD, and its alteration in level may be connected with disease
      activity and severity.

PMID- 16304264
TI  - Paired inspiratory/expiratory volumetric thin-slice CT scan for emphysema
      analysis: comparison of different quantitative evaluations and pulmonary function
      test.
AB  - PURPOSES: The aim of the study was to use three-dimensional high-resolution CT
      scan data sets in inspiration and expiration for the quantitative evaluation of
      emphysema. Using an advanced dedicated semiautomatic analysis tool, the
      functional inspiratory/expiratory shifts of emphysema volume and clusters were
      quantified. The pulmonary function test (PFT) served as the clinical "gold
      standard." MATERIALS AND METHODS: Thirty-one patients (9 women and 22 men; mean
      [+/- SD] age, 60 +/- 8 years) who had severe emphysema due to COPD (Global
      Initiative for Chronic Obstructive Lung Disease [GOLD] class III and IV) were
      included in the study. All patients underwent paired inspiratory/expiratory
      multidetector CT scans (slice thickness, 1/0.8 mm) and pulmonary function tests
      (PFTs). CT scan data were analyzed with self-written emphysema detection
      solftware. It provides lung volume (LV), emphysema volume (EV), emphysema index
      (EI), and four clusters of emphysema with different volumes (from 2, 8, 65, and
      120 mm(3)). These results were correlated with total lung capacity (TLC),
      intrathoracic gas volume (ITGV), and residual volume (RV) derived from PFT
      results. RESULTS: Inspiratory LV correlated with TLC (r = 0.9), expiratory LV
      with ITGV (r = 0.87), and RV (r = 0.83). Expiratory EV correlated better with
      ITGV (r = 0.88) and RV (r = 0.93) than with inspiratory EV (r = 0.83 and 0.88,
      respectively). The mean inspiratory EI was 54 +/- 13%, and it decreased to 43 +/-
      15% in expiration. However, the individuals showed a broad spectrum of changes of
      EI (mean, 11%; range, 1 to 28%), and no differences in inspiratory/expiratory EI
      and changes in EI or LV were found between GOLD III and GOLD IV patients. In
      expiration, there was a change from the large emphysema cluster (-37%) to the
      intermediate cluster (+15%) and small cluster (+13% and +11%, respectively). The
      change of volume of the large emphysema cluster after expiration correlated well
      with the changes in LV (r = 0.9), EV (r = 0.99), EI (r = 0.85), and MLD (r =
      0.76). CONCLUSION: Emphysema volumes measured from expiratory MDCT scans better
      reflect PFT abnormalities in patients with severe emphysema than those from
      inspiratory scans. Volumetric cluster analysis provided deeper insights into the
      local hyperinflation and expiratory obstruction of large emphysematous clusters.

PMID- 16304265
TI  - Effects of lung volume reduction surgery on sleep quality and nocturnal gas
      exchange in patients with severe emphysema.
AB  - STUDY OBJECTIVES: We hypothesized that associated with improvements in
      respiratory mechanics, lung volume reduction surgery (LVRS) would result in an
      improvement in both sleep quality and nocturnal oxygenation in patients with
      severe emphysema. DESIGN: Prospective randomized controlled trial. SETTING:
      University hospital. PATIENTS: Sixteen patients (10 men, 63 +/- 6 years [+/- SD])
      with severe airflow limitation (FEV(1), 28 +/- 10% predicted) and hyperinflation
      (total lung capacity, 123 +/- 14% predicted) who were part of the National
      Emphysema Treatment Trial. INTERVENTIONS AND MEASUREMENTS: Patients completed 6
      to 10 weeks of outpatient pulmonary rehabilitation. Spirometry, measurement of
      lung volumes, arterial blood gas analysis, and polysomnography were performed
      prior to randomization and again 6 months after therapy. Ten patients underwent
      LVRS and optimal medical therapy, while 6 patients received optimal medical
      therapy only. RESULTS: Total sleep time and sleep efficiency improved following
      LVRS (from 184 +/- 111 to 272 +/- 126 min [p = 0.007], and from 45 +/- 26 to 61
      +/- 26% [p = 0.01], respectively), while there was no change with medical therapy
      alone (236 +/- 75 to 211 +/- 125 min [p = 0.8], and from 60 +/- 18 to 52 +/- 17%
      [p = 0.5], respectively). The mean and lowest oxygen saturation during the night
      improved with LVRS (from 90 +/- 7 to 93 +/- 4% [p = 0.05], and from 83 +/- 10 to
      86 +/- 10% [p = 0.03], respectively), while no change was noted in the medical
      therapy group (from 91 +/- 5 to 91 +/- 5 [p = 1.0], and from 84 +/- 5 to 82 +/-
      6% [p = 0.3], respectively). There was a correlation between the change in FEV(1)
      and change in the lowest oxygen saturation during the night (r = 0.6, p = 0.02).
      In addition, there was an inverse correlation between the change in the lowest
      oxygen saturation during the night and the change in residual volume (- r = 0.5,
      p = 0.04) and functional residual capacity (- r = 0.6, p = 0.03). CONCLUSION: In
      patients with severe emphysema, LVRS, but not continued optimal medical therapy,
      results in improved sleep quality and nocturnal oxygenation. Improvements in
      nocturnal oxygenation correlate with improved airflow and a decrease in
      hyperinflation and air trapping.

PMID- 16304266
TI  - Susceptibility pattern and epidemiology of Mycobacterium tuberculosis in a Saudi
      Arabian hospital: a 15-year study from 1989 to 2003.
AB  - OBJECTIVES: The objective of this study was to examine the prevalence and trends
      of drug resistance of Mycobacterium tuberculosis at the Saudi Aramco Medical
      Services Organization. METHODS: We retrospectively identified M tuberculosis
      isolates from January 1989 to December 2003. Antimicrobial susceptibility and
      clinical data were collected and analyzed. RESULTS: From 1989 to 2003, 276
      nonrepetitive culture-positive cases were identified. There were 236 Saudis
      (84.6%), and the remainder were non-Saudis (15.4%). M tuberculosis isolates were
      obtained from pulmonary specimens (49%) and extrapulmonary sites (51%). The
      resistance rates of M tuberculosis to tested first-line agents were as follows:
      isoniazid, 12.5%; ethambutol, 7.5%; streptomycin; 6.9%; and rifampin, 1.1%. The
      resistance rate to isoniazid and streptomycin was 1.8%, the rate to isoniazid and
      rifampin was 0.7%, and the rate to isoniazid and ethambutol was 2.5%. The
      resistance rate to isoniazid, ethambutol, and streptomycin was 0.7% CONCLUSION: M
      tuberculosis resistance to isoniazid showed a decreased rate over the study
      period from 20 to 5.7%. The rate of multidrug-resistant M tuberculosis remained
      low.

PMID- 16304267
TI  - Etiology and outcome of community-acquired pneumonia in patients with diabetes
      mellitus.
AB  - STUDY OBJECTIVES: It has been suggested that diabetes mellitus is associated with
      an increased susceptibility to infection, the risk of using more aggressive
      therapeutic agents, and increased morbidity and mortality; however, current
      evidence supporting these events in the field of pneumonia is scarce. The aim of
      the present study was to provide information on clinical and microbiological
      characteristics and the outcome of community-acquired pneumonia in patients with
      diabetes mellitus. DESIGN: Prospective study of cases. SETTING: A university
      hospital in Lleida, Spain. PATIENTS: During a 5-year period, we prospectively
      studied the clinical and radiologic characteristics, the spectrum of causative
      agents and other microbiological data, and the outcomes of 660 consecutive
      episodes of community-acquired pneumonia. Data derived from 106 patients with
      diabetes mellitus were analyzed and compared with data obtained from the
      remaining population. MEASUREMENTS AND RESULTS: Patients with diabetes mellitus
      were significantly older (p = 0.001) and more frequently had other concomitant
      comorbid conditions (p = 0.018). Diabetes was also significantly associated with
      the development of pleural effusion (p = 0.015) and mortality (p = 0.002); for
      both events, diabetes remained as an independent predictive factor in
      multivariate analyses. By contrast, the incidence of the main etiologic agents,
      and the bacteremia or empyema rates did not show significant differences in
      relation to the remaining patients. In the subgroup of patients with diabetes,
      mortality was associated with the presence of multilobar infiltrates (p = 0.004),
      concomitant underlying diseases (p = 0.004), and some diabetes-related
      complications (nephropathy, p = 0.040; and vasculopathy, p = 0.002), although
      only multilobar infiltrates and comorbidities were selected as prognostic factors
      in the multivariate analysis. CONCLUSIONS: In patients with community-acquired
      pneumonia, diabetes mellitus is associated with a poor prognosis, increasing the
      rate of pleural effusion and mortality. Our results suggest that this adverse
      outcome is more attributable to the underlying circumstances of patients than to
      uncommon microbiological findings.

PMID- 16304268
TI  - Resolution of residual pleural disease according to time course in tuberculous
      pleurisy during and after the termination of antituberculosis medication.
AB  - STUDY OBJECTIVES: To assess the resolution of pleural disease in patients with
      tuberculous pleurisy (TP) during and after antituberculosis medication. DESIGN:
      An observational, prospective, longitudinal study. SETTING: University-affiliated
      general hospital in Seoul, Korea. PATIENTS AND METHODS: Chest radiographs of 85
      adult TP patients were followed up prospectively from diagnosis to 24 months
      after the start of medication. The extent of pleural disease, synonymous with the
      radiographic term, pleural opacity (PO), was evaluated at regular intervals
      according to a size scale. Additionally, following completion of 6 months of
      therapy, residual PO (RPO) was determined by either measurement of the widest
      width of the opacity, if loculated, or at the superior level of the
      hemidiaphragm. RESULTS: Seventy-seven patients had a PO graded > or = 2 at the
      initial presentation. At 6, 9, and 24 months, the number of patients with these
      grades declined. At these time periods, there were 14, 8, and 7 patients,
      respectively, remaining with this classification. RPO > 10 mm at 24 months was
      considered indicative of significant residual pleural disease. During the period
      after 6 months of antituberculosis medication, the number of patients with RPO >
      or = 10 mm declined from 43 patients at 6 months to 21 patients at 24 months. The
      presence of loculation on an initial chest decubitus view was associated with
      significant RPO at 24 months (p = 0.009). CONCLUSION: In TP patients, improvement
      of RPO often occurred even after completion of 6 months of antituberculosis
      medication up to 24 months. A loculated PO at initial presentation, but not
      initial PO size, was a predictor of significant RPO at 24 months.

PMID- 16304269
TI  - A cost-minimization analysis comparing azithromycin-based and levofloxacin-based
      protocols for the treatment of patients hospitalized with community-acquired
      pneumonia: results from the CAP-IN trial.
AB  - BACKGROUND: A randomized trial was performed comparing azithromycin and
      levofloxacin for treating moderately to severely ill patients hospitalized with
      community-acquired pneumonia. This is a cost-minimization analysis comparing
      those regimens. METHODS: The cost-minimization analysis compares 81 patients
      receiving sequential therapy with IV azithromycin plus IV ceftriaxone followed by
      oral azithromycin with 82 patients receiving IV levofloxacin followed by oral
      levofloxacin, all with complete economic data over approximately 30 days,
      including information about hospitalization, study medications, home care,
      postdischarge utilization, and lost productivity. Units of utilization were
      multiplied by unit prices in order to estimate cost per patient. These total
      costs were compared using a two-sample t test. RESULTS: Direct medical costs of
      the azithromycin group were 2,481 US dollars less than the corresponding costs in
      the levofloxacin group (p = 0.03; 95% confidence interval, 238 US dollars to
      4,724 US dollars). Most of the cost difference (2,300 US dollars) is attributable
      to hospital days, with the majority of these days being spent on the general
      medicine wards. The precise magnitude of the cost advantage attributable to
      azithromycin, if any, depends on both the reduction in length of hospital stay
      and its associated daily cost. CONCLUSIONS: Azithromycin was no more costly than
      levofloxacin, and perhaps less so. Cost is but one of many factors that should be
      considered by clinicians in decisions involving any individual patient.

PMID- 16304270
TI  - Diameter of non-small cell lung cancer correlates with long-term survival:
      implications for T stage.
AB  - STUDY OBJECTIVES: To determine the effect of tumor diameter on the long-term
      survival of patients with stage I non-small cell lung cancer (NSCLC) within a
      large multi-institutional database, and to assess the accuracy of the T
      descriptor threshold of 3 cm. DESIGN AND PATIENTS: A total of 9,191 patients > or
      = 20 years old with surgically treated stage I NSCLC < or = 6 cm registered in
      the Surveillance, Epidemiology, and End Results database from 1992 to 1997 were
      included. The size of the nodule was grouped into six categories: < 1 cm (n =
      191, 2%), 1 to 1.9 cm (n = 2,130, 23%), 2 to 2.9 cm (n = 2,851, 31%), 3 to 3.9 cm
      (n = 1,984, 22%), 4 to 4.9 cm (n = 1,161, 13%), and 5 to 6 cm (n = 874, 9%). Due
      to its limited sample size, subcentimeter nodules were not included in the
      survival analysis. Survival analyses were performed with Kaplan-Meier estimates,
      log-rank tests, and Cox proportional hazards models. MEASUREMENTS AND RESULTS: A
      total of 4,904 (53%) men and 4,287 women (mean +/- SD age, 66.6 +/- 9.4 years)
      with stage I NSCLC were analyzed. The use of lobectomies and pneumonectomies as
      surgical treatment instead of limited resections increased with the size of the
      tumor, from 62% in subcentimeter nodules to 96% in 5- to 6-cm tumors (p <
      0.0001). Survival decreased with increasing size of the tumor (p < 0.0001). There
      was a significant survival difference when size groups were compared to tumors
      1.0 to 1.9 cm: 2.0 to 2.9 cm (hazard ratio [HR], 1.3; 95% confidence interval
      [CI], 1.16 to 1.47), 3.0 to 3.9 cm (HR, 1.49; 95% CI, 1.32 to 1.69), 4.0 to 4.9
      cm (HR, 1.82; 95% CI, 1.59 to 2.08), and 5.0 to 6.0 cm (HR, 2.04; 95% CI, 1.77 to
      2.36). Survival was similar in tumors between 2.0 to 2.9 cm and 3.0 to 3.9 cm,
      and in tumors between 4.0 to 4.9 cm and 5.0 to 6.0 cm. CONCLUSIONS: The T
      descriptor should be changed so that T1 is reserved for tumors < 2 cm. Further
      refinement of larger tumors into T2a (2 to 3.9 cm) and T2b (> or = 4 cm) should
      be considered.

PMID- 16304271
TI  - The pulmonary status of patients with limited-stage small cell lung cancer 15
      years after treatment with chemotherapy and chest irradiation.
AB  - STUDY OBJECTIVES: To describe pulmonary symptoms, signs, pulmonary function, and
      lung imaging studies in patients with limited-stage small cell lung cancer (SCLC)
      2 to 15 years after receiving treatment with chemotherapy and chest radiotherapy.
      DESIGN: Retrospective review of clinical records and radiographic studies of
      patients treated in three different prospective combined-modality studies.
      SETTING: Federal hospital. PATIENTS: One hundred fifty-six patients with SCLC who
      were enrolled between 1974 and 1994. INTERVENTIONS: Patients with limited-stage
      SCLC treated on prospective therapeutic studies of combined chemotherapy and
      radiation therapy were identified. Pulmonary symptoms, physical findings,
      pulmonary function tests, arterial blood gas measurements, and chest imaging
      studies were assessed at baseline, and at 1 to 2 years, at 3 to 5 years, and at >
      5 years following the initiation of treatment. MEASUREMENTS AND RESULTS: Initial
      symptoms included cough in 84 (55%), dyspnea in 59 (39%), and sputum production
      in 26 (17%). Twenty-three patients lived beyond 5 years (15%) without evidence of
      recurrence. Seven of these 5-year survivors were without pulmonary symptoms.
      Pulmonary function test results showed no significant changes in percent
      predicted values for FVC, FEV(1), and FEV(1)/FVC ratio over the time periods
      reviewed. The percent predicted values for the diffusing capacity of the lung for
      carbon monoxide decreased from 71% before the start of treatment to 56% (p <
      0.032) at 1 to 2 years. Values improved in most patients beyond 5 years after
      starting treatment. Radiologist interpretations of chest imaging studies were
      available for 17 of 23 patients surviving > 5 years. Most patients had minimal to
      no changes in imaging study findings beyond 5 years. CONCLUSIONS: Long-term
      survivors with limited-stage SCLC who were treated with combined chemotherapy and
      chest radiotherapy have minimal changes in pulmonary symptoms or function from 5
      to 15 years after the start of treatment. A concern for late toxicity from
      combined-modality therapy should not dissuade clinicians from offering therapy
      with potentially curative result with minimal to no pulmonary dysfunction.

PMID- 16304272
TI  - Prediction of lung adenocarcinoma without vessel invasion: a CT scan volumetric
      analysis.
AB  - STUDY OBJECTIVES: Patients with lung adenocarcinoma without vessel invasion have
      a favorable prognosis after resection and are among the candidates for limited
      surgery. The purpose of the present study was to predict lung adenocarcinoma
      without vessel invasion based on a volumetric analysis of the lesion with a CT
      scan prior to the operation. METHODS: CT scan images were obtained in 288
      consecutive patients with adenocarcinoma of the lung before surgical resection.
      Total tumor volume, the volume of the nonsolid component, and the proportion
      occupied by the nonsolid component were calculated by the perimeter method. The
      performance of the derived logistic regression model and the volumetric results
      were evaluated by receiver operating characteristic analysis. The model derived
      for the prediction of tumors without vessel invasion was assessed by means of the
      leave-one-out cross-validation technique. RESULTS: The pathologic diagnosis was
      adenocarcinoma with vessel invasion in 160 cases, and without vessel invasion in
      128 cases. The median total tumor volume, the median volume of the nonsolid
      component, and median proportion occupied by the nonsolid component were 1,123.7
      mm(3), 253.4 mm(3), and 58.0%, respectively. With the derivation of the
      predictive rule, stepwise regression yielded the following five features: the
      proportion occupied by the nonsolid component; spiculation; pleural indentation;
      gender; and tumor size. The Az value, a measure of diagnostic power represented
      as the area under the curve, was 0.957 for prediction of lung adenocarcinoma
      without vessel invasion. The cross-validation accuracy achieved by applying the
      rule was 90.3%. CONCLUSIONS: The proportion occupied by the nonsolid component
      based on a CT scan volumetric analysis was a reliable predictor of tumors without
      vessel invasion in patients with adenocarcinoma of the lung.

PMID- 16304273
TI  - A retrospective analysis of the management of parapneumonic empyemas in a county
      teaching facility from 1992 to 2004.
AB  - OBJECTIVES: To characterize how patients with empyemas are managed initially at
      our facility and to determine how "less aggressive" treatments (eg, no drainage,
      repeat thoracentesis, or tube thoracostomy) affect short-term outcomes (ie,
      inpatient mortality and the need for a second intervention) compared to "more
      aggressive" treatments (eg, intrapleural fibrinolytic agents, video-assisted
      thoracoscopic surgery, or other surgery). We will also assess whether earlier
      diagnosis, earlier antibiotic treatment, fewer patient comorbidities, and
      consulting appropriate services improve mortality. DESIGN: Retrospective chart
      analysis. SETTING: County teaching hospital in Los Angeles, CA. PATIENTS: Seventy
      two adult inpatients with parapneumonic empyemas. INTERVENTIONS: Mortality and
      the need for second intervention rates were calculated and compared with data
      published in the 2000 American College of Chest Physicians consensus statement on
      the management of parapneumonic effusions using the Fisher exact test.
      Comparisons were made between empyema survivors and nonsurvivors using t tests
      and chi(2) tests. RESULTS: All 72 patients were managed with less aggressive
      initial treatments. There were no differences in mortality when our patients were
      compared to the less aggressive group from the literature (6% vs 9%,
      respectively; p = 0.40; relative risk, 0.6; 95% confidence interval [CI], 0.23 to
      1.62) or the more aggressive group from the literature (6% vs 3%, respectively; p
      = 0.29; relative risk, 1.8; 95% CI, 0.64 to 5.23). There was no difference
      between the second intervention rate of our patients and that of the less
      aggressive group from the literature (47% vs 43%, respectively; p = 0.47;
      relative risk, 1.1; 95% CI, 0.86 to 1.42), although there was a difference when
      compared to the more aggressive group (47% vs 11%, respectively; p < 0.0001;
      relative risk, 4.5; 95% CI, 3.20 to 6.31). There were no statistically
      significant differences in time of diagnosis, the timing of antibiotic treatment,
      the number of patient comorbidities, or the number of services consulted when
      survivors and nonsurvivors from the study were compared. CONCLUSIONS: Patients
      with empyemas at our hospital are treated with less aggressive initial treatments
      and have a higher second intervention rate when compared to patients described in
      the literature who were initially managed with more aggressive treatments.

PMID- 16304274
TI  - Increased oxidative stress in exudative pleural effusions: a new marker for the
      differentiation between exudates and transudates?
AB  - STUDY OBJECTIVES: Oxidative stress has been associated with various respiratory
      disorders. We tested the hypothesis that exudates would present higher levels of
      oxidative stress compared to transudates, expressing the increased local
      oxidative burst in the former. DESIGN: Prospective, cross-sectional study.
      PATIENTS OR PARTICIPANTS: One hundred six consecutive patients who had undergone
      thoracentesis were studied. Ninety patients with a final diagnosis of pleural
      effusion were further analyzed. SETTING: The respiratory department and a
      clinical laboratory of a tertiary hospital. INTERVENTIONS: Subjects underwent
      diagnostic thoracentesis, and standard biochemical parameters (ie, total protein,
      lactate dehydrogenase, and albumin levels) were measured in pleural fluid and
      serum. Oxidative stress levels were assessed with a commercially available method
      (d-ROMs test; Diacron; Grosseto, Italy) that uses conventional Carratelli units
      (UCarr). In 14 patients, duplicate measurements of oxidative stress and a second
      thoracentesis were performed on the following day for the assessment of the
      repeatability of measurements. Receiver operating characteristic (ROC) analysis
      was performed in order to determine the optimal cutoff level for the
      differentiation between exudates and transudates. MEASUREMENTS AND RESULTS:
      Oxidative stress levels were higher in exudates compared to transudates (mean [+/
      SD] stress level, 274 +/- 72 vs 126 +/- 34 UCarr, respectively; p < 0.0001). No
      significant differences were found among the levels of oxidative stress in
      exudative effusions of different etiologies. The area under the ROC curve was
      0.992 (95% confidence interval, 0.945 to 0.997), and the method provided high
      sensitivity (96.8%), high specificity (96.3%), and high accuracy (96.7%) for the
      diagnosis of exudates at a cutoff level for oxidative stress of 186 UCarr.
      Consecutive measurements of oxidative stress in the same samples and on fluid
      from two different thoracenteses performed on 2 consecutive days presented
      excellent repeatability. CONCLUSIONS: Oxidative stress levels are higher in
      exudative pleural effusions compared to transudative effusions, probably due to
      reactive oxygen species produced in the former.

PMID- 16304275
TI  - Spontaneous pneumomediastinum: a benign curiosity or a significant problem?
AB  - OBJECTIVE: To identify the significance of spontaneous pneumomediastinum (SPM)
      and to optimize its management. METHODS: A retrospective analysis was undertaken
      of all patients presenting with SPM over a 5-year period. Eighteen patients were
      identified, and information on their presentations, initial diagnoses,
      comorbidities, investigations, clinical courses, length of hospital stays, and
      outcomes were collated. SETTING: The emergency department referrals of two major
      Melbourne teaching hospitals. RESULTS: SPM is an uncommon condition presenting in
      approximately 1 in 30,000 emergency department referrals. The typical patient
      identified from this study is a young man who is likely to have a history of
      asthma, and who is also likely to smoke or to use illicit drugs. The most common
      presentation is nonspecific pleuritic chest pain with dyspnea. Complications are
      rare, and the clinical course benign, but the possibility of a ruptured viscus or
      an initial misdiagnosis often leads to a great number of investigations. A
      proposed algorithm of management is given. Other serious and potentially life
      threatening conditions, such as Boerhaave syndrome need to be excluded.

PMID- 16304276
TI  - Treatment of sonographically stratified multiloculated thoracic empyema by
      medical thoracoscopy.
AB  - INTRODUCTION: In cases of empyema, some form of intervention, either chest tube
      drainage, thoracoscopy, video-assisted thoracic surgery (VATS), or thoracotomy,
      with or without pleural fibrinolysis, is required. What the best approach is and
      when and how to intervene is a matter of debate. STUDY OBJECTIVE: To analyze the
      safety and outcome of medical thoracoscopy in the treatment of multiloculated
      empyema. METHODS: We report a retrospective series of 127 patients with thoracic
      empyema treated with medical thoracoscopy from 1989 to 2003 in three hospitals in
      Switzerland and Italy. All patients had multiloculated empyema as identified by
      chest ultrasonography. In the absence of multiloculation, or in case of
      fibrothorax, simple chest tube drainage or surgical VATS/thoracotomy were
      performed, respectively. RESULTS: Mean age +/- SD was 58 +/- 18 years (range, 9
      to 93 years). In 47%, a microbiological diagnosis was made. Complications
      occurred in 9% of patients (subcutaneous emphysema, n = 3; air leak of 3 to 7
      days, n = 9). No mortality was observed. Forty-nine percent of patients received
      postinterventional intrapleural fibrinolysis. Medical thoracoscopy was primarily
      successful in 91% of cases. In four patients, the insertion of an additional
      chest tube or a second medical thoracoscopy was required. Finally, 94% of
      patients were cured by nonsurgical means. Six percent of patients required
      surgical pleurectomy, mostly through thoracotomy. CONCLUSION: Multiloculated
      empyema as stratified by ultrasonography can safely and successfully be treated
      by medical thoracoscopy.

PMID- 16304277
TI  - Histopathologic features and outcome of patients with acute exacerbation of
      idiopathic pulmonary fibrosis undergoing surgical lung biopsy.
AB  - STUDY OBJECTIVES: To define the clinicopathologic features and outcome of acute
      exacerbation in patients with idiopathic pulmonary fibrosis (IPF) undergoing
      surgical lung biopsy. DESIGN: Retrospective, single-center study. SETTING:
      Tertiary care, referral medical center. PATIENTS: Seven patients with acute
      exacerbation of IPF who underwent surgical lung biopsy. RESULTS: The median age
      of these seven patients was 70 years (range, 59 to 74 years); two were women.
      Five patients had a smoking history and included two current smokers. All
      patients were experiencing an exacerbation of dyspnea for a median duration of 14
      days (range, 7 to 28 days) prior to presentation. In three of these patients, the
      acute deterioration was the presenting feature of IPF, while in the remaining
      four patients the diagnosis of IPF had previously been established. Chest
      radiography demonstrated bilateral mixed alveolar-interstitial infiltrates in all
      of them. CT revealed ground-glass opacities and consolidation bilaterally in all
      patients with associated peripheral honeycombing in six of them. Echocardiography
      was performed in six patients and demonstrated pulmonary hypertension in all. BAL
      fluid was obtained in five patients and revealed neutrophilia in all. Surgical
      lung biopsy showed diffuse alveolar damage (DAD) in five patients with associated
      collagen fibrosis and honeycomb changes typical of usual interstitial pneumonia
      (UIP). One biopsy showed a combination of UIP and organizing pneumonia, while one
      biopsy showed only DAD. Despite treatment with lung-protective ventilation
      strategies and high-dose systemic corticosteroids, six patients (86%) died during
      their hospitalization. CONCLUSIONS: Although IPF is typically associated with an
      insidious, slowly progressive clinical course, acute exacerbations occur and may
      be the presenting manifestation in some patients. In either situation, current
      management strategies including high-dose corticosteroid therapy appear to be
      relatively ineffective for these patients with acute exacerbation undergoing
      surgical lung biopsy.

PMID- 16304278
TI  - The effects of hyperpnea on exhaled nitric oxide synthesis in normal subjects.
AB  - STUDY OBJECTIVES: To determine if the concentration of nitric oxide (NO) in the
      lungs increases with hyperpnea by contrasting calculated production (ie, the
      product of the fractional expired NO concentration [FeNO] and minute ventilation
      [Ve]) [Vno] with the amount of NO in equilibrium with the conducting airways
      (eNOair) and the amount of NO diffusing from the alveoli (eNOalv). DESIGN:
      Observational study. SETTING: University teaching hospital. PARTICIPANTS: Normal
      subjects. INTERVENTIONS: Measurements were made in 16 healthy people during and
      after 4 min of tidal breathing (10 L/min) and isocapnic hyperventilation of 60
      L/min. MEASUREMENTS AND RESULTS: FeNO was measured by collecting the exhaled air
      during the last minute of each trial and passing it through a chemiluminescence
      analyzer. The expired NO levels in the plateau phases of slow (30 mL/s) and fast
      (200 mL/s) single-breath exhalations were also obtained before and after
      hyperventilation. The Vno (mean +/- SEM) increased from 89.8 +/- 12.3 to 329.1 +/
      36.2 nL/min as Ve rose (p < 0.001). However, neither the quantities of eNOair
      nor eNOalv changed with hyperventilation (eNOair range before to after, 34.9 +/-
      7.7 to 30.9 +/- 6.4 parts per billion [ppb], p = 0.96; eNOalv range before to
      after, 7.3 +/- 1.5 to 6.5 +/- 1.1 ppb, p = 0.97). CONCLUSIONS: These data
      demonstrate that the amount of NO in equilibrium with the airway walls and
      alveoli are not altered by hyperpnea. Rather, the apparent augmentation in Vno in
      such circumstances appears to be an arithmetic artifact.

PMID- 16304279
TI  - Palliative treatment of dyspnea with epidural methadone in advanced emphysema.
AB  - STUDY OBJECTIVES: This study investigated whether epidural methadone perfusion at
      the thoracic level can mitigate dyspnea in patients with advanced emphysema.
      DESIGN: Open-label clinical trial without a control group. SETTING: University
      hospital. PATIENTS: The inclusion criteria were a diagnosis of emphysema, basal
      dyspnea index (Mahler scale) < or = 3, FEV(1) < or = 35%, and no indication for
      pneumoreduction or lung transplantation surgery. INTERVENTIONS: An epidural
      catheter was inserted at the thoracic level connected to a perfusion pump for
      administering methadone (6 mg/24 h). Assessments were made at baseline, 1 week,
      and 1 month after catheter insertion. MEASUREMENTS: Pulmonary function tests were
      performed, and determinations were made of arterial blood gas levels, respiratory
      control data, dyspnea quantification by Mahler transitional dyspnea index (TDI),
      and the Borg scale change with inspiratory resistive loading, 6-min walk (6MW)
      distance, and health-related quality of life using the Chronic Respiratory
      Disease Questionnaire. RESULTS: Of the nine patients studied, infection and
      catheter migration lead to suspension of treatment before the end of the study in
      two cases. A significant improvement in dyspnea occurred by 1 week: mean TDI,
      3.77 (SD, 1.98) [p < 0.01]. After 1 month of treatment, there were significant
      improvements in the 6MW distance (mean, 35.33 m; SD, 17.03; p < 0.05), health
      related quality of life (mean, 1.63; SD, 0.36; p < 0.05), and dyspnea (mean TDI,
      5.33; SD, 2.16; p < 0.05). In addition, after 1 month, Paco(2) fell by 6.67 mm Hg
      (p < 0.05) and rapid shallow breathing index decreased from 38 to 27 (p < 0.05).
      These changes occurred without any alteration in the subject's ability to
      perceive or respond to inspiratory loading. CONCLUSION: Epidural methadone
      perfusion at chest level can effectively palliate dyspnea and improve exercise
      capacity and quality of life in patients with advanced emphysema, without
      deterioration in respiratory control or lung function. These data suggest that
      modulation of spinal cord afferent signaling is an appropriate novel target for
      dyspnea control in chronic respiratory disease.

PMID- 16304280
TI  - Interpretation of cough provoked by airway challenges.
AB  - STUDY OBJECTIVE: To analyze the cough response to three airway challenges in
      order to clarify whether the recording of the provoked coughs would be beneficial
      in the management of asthma. DESIGN: A prospective study. SETTING: University
      hospital. PARTICIPANTS: Fifteen healthy subjects, 16 steroid-naive subjects with
      asthma, and 16 subjects with steroid-treated asthma. INTERVENTIONS: Inhalation
      challenges with isotonic histamine, hypertonic saline solution, and hypertonic
      histamine, using an ultrasonic nebulizer and 2-min tidal breathing method.
      MEASUREMENTS: Airflow parameters were measured with a spirometer, and the coughs
      were recorded manually. RESULTS: Coughing during the isotonic histamine challenge
      was associated with the degree of the bronchoconstriction induced. When this was
      taken into account, the healthy subjects coughed as frequently as the asthmatic
      subjects. During the two hypertonic challenges, the asthmatic subjects coughed
      more frequently than did the healthy subjects when the induced
      bronchoconstriction had not yet developed. At that stage of the hypertonic saline
      solution challenge, the mean coughing frequency was 0.7 coughs per minute (95%
      confidence interval [CI], 0.03 to 1.3 coughs per minute) for the healthy
      subjects, 2.7 coughs per minute (95% CI, 0.8 to 4.5 coughs per minute) for the
      steroid-naive asthmatic subjects, and 1.3 coughs per minute (95% CI, 0.6 to 1.9
      coughs per minute) for the steroid-treated asthmatic subjects (p = 0.018). For
      the hypertonic histamine challenge, the respective values were 0.8 coughs per
      minute (95% CI, 0.4 to 1.2 coughs per minute), 3.6 coughs per minute (95% CI, 2.4
      to 4.9 coughs per minute), and 2.1 coughs per minute (95% CI, 1.0 to 3.1 coughs
      per minute; p = 0.001). This cough did not correlate with airway
      hyperresponsiveness. CONCLUSIONS: Coughing during isotonic histamine challenge
      seems to be a manifestation of bronchoconstriction, and recording of the coughs
      may not provide additional information to airflow measurements. Frequent coughing
      during hypertonic saline solution and hypertonic histamine challenges in the
      absence of bronchoconstriction is a pathologic phenomenon. Sensitivity to the
      cough-provoking effect of hypertonic challenges seems to be enhanced in patients
      with asthma but unrelated to airway hyperresponsiveness. Therefore, the recording
      of the provoked coughs during these challenges may add to the information
      obtained from airflow measurements.

PMID- 16304281
TI  - Factors associated with dyspnea in adult patients with sickle cell disease.
AB  - OBJECTIVE: The aim of this prospective study was to determine the
      cardiorespiratory factors associated with dyspnea in patients with sickle cell SS
      hemoglobin disease, with a specific interest in lung vascular involvement.
      MEASUREMENTS: Forty-nine patients (29 women and 20 men; mean [+/- SD] age: women,
      29 +/- 6 years; men, 31 +/- 11 years) underwent direct evaluations (Borg scale
      evaluation during a 6-min walk test) and indirect evaluations (modified Medical
      Research Council [MRC]score) of their dyspnea, pulmonary function tests (PFTs)
      [spirometry, volumes, diffusing capacity of the lung for carbon monoxide (Dlco),
      diffusing capacity of the alveolar-capillary membrane, and pulmonary capillary
      blood volume measurements], echocardiography, and biological evaluation. RESULTS:
      Thirty-four patients complained of significant breathlessness (MRC score, > 1).
      Indirect and direct evaluations of dyspnea were correlated. PFT results depicted
      a very mild restrictive pattern (mean total pulmonary capacity, 86 +/- 11%
      predicted) and an impairment of Dlco (mean Dlco corrected for the degree of
      anemia, 69 +/- 13% predicted). The statistical analysis demonstrated that dyspnea
      and exercise performance were closely linked to indexes of Dlco but not with any
      echocardiographic or biological measure including anemia. Nevertheless, only
      approximately 25% of the variability was explained by these associations. Despite
      having a similar history of vasoocclusive crisis events, women had more severe
      anemia, dyspnea, decreases in Dlco (corrected for the degree of anemia), and a
      higher capillary blood volume (corrected for alveolar volume) than men.
      CONCLUSION: Lung vascular disease contributes to dyspnea and the exercise
      limitation of patients with sickle cell disease. A sequential assessment of Dlco
      would therefore constitute one of the objective functional end points for follow
      up studies of these patients.

PMID- 16304282
TI  - Differentiation between the sensory and affective dimension of dyspnea during
      resistive load breathing in normal subjects.
AB  - STUDY OBJECTIVE: Dyspnea is the uncomfortable sensation of breathing and is an
      impairing symptom in a variety of diseases. Like pain, it motivates adaptive
      behavior to regain homeostasis, and both sensations share various
      characteristics. Whereas the realization of the multidimensionality of pain was a
      key contribution to pain research, little is known about a similar
      multidimensionality in the perception of dyspnea. The present study examined
      whether sensory and affective aspects of induced dyspnea can be differentiated.
      DESIGN: A controlled laboratory study. SETTING: Psychophysiologic laboratory of
      the Psychological Institute III, University of Hamburg, Germany. PARTICIPANTS:
      Ten healthy volunteers aged 24 to 52 years (mean, 35 years). INTERVENTIONS:
      Dyspnea was induced by breathing through inspiratory resistive loads of
      increasing magnitude (0.99 to 2.33 kPa/L/s), alternating with episodes of
      unloaded breathing. Inspiratory time (Ti) and breathing frequency (f) were
      continuously monitored. The experienced intensity and unpleasantness of dyspnea
      were rated after each episode on separate visual analog scales (VASs), which were
      presented in permuted order. Intraindividual linear regression slopes were
      calculated separately for both dimensions and compared. MEASUREMENTS AND RESULTS:
      Breathing through inspiratory resistive loads resulted in increases of VAS
      ratings for intensity and unpleasantness paralleled by increases in Ti and
      decreases in f (p = 0.012 and p = 0.003, respectively). The mean regression slope
      for perceived unpleasantness was higher than for perceived intensity (mean +/-
      SD, 2.83 +/- 1.28 and 2.11 +/- 1.74, respectively; p = 0.032), indicating
      stronger increases of unpleasantness with increasing magnitude of resistive
      loads. CONCLUSIONS: The results show that the sensory and affective dimension of
      experimentally induced dyspnea can be differentiated in healthy volunteers. The
      obtained multidimensionality of dyspnea converges with previous reports on
      similarities between dyspnea and pain. Implications for future studies on the
      perception of dyspnea are provided.

PMID- 16304283
TI  - Rapid eye movement-related disordered breathing: clinical and polysomnographic
      features.
AB  - OBJECTIVE: The existence of a rapid eye movement (REM)-specific sleep-disordered
      breathing (SDB) has been suggested based on the finding of an association between
      sleepiness and respiratory disturbances confined primarily to REM sleep. The aim
      of the study was to define the frequency and the clinical and polysomnographic
      features of REM SDB in a large clinical population. METHODS: Anthropometric,
      clinical, and polysomnographic characteristics of 415 patients undergoing
      polysomnography for SDB were examined. For all patients the apnea-hypopnea index
      (AHI) during total sleep time, the AHI during REM (AHI-REM), and the AHI during
      non-REM sleep (AHI-NREM) were calculated. REM SDB was defined as an AHI-REM/AHI
      NREM ratio >2. Patients were stratified according to the severity of disease in
      mild, moderate, and severe cases. Daytime sleepiness was assessed subjectively by
      the Epworth sleepiness scale (ESS), and objectively, in a subgroup of 228
      patients, by the maintenance wakefulness test (MWT). RESULTS: Of the initial
      sample, 36.4% of cases (n = 151) fulfilled the REM SDB criteria. No significant
      differences in subjective complaints, medical history, and drug intake were
      present between REM and non-REM SDB patients, and no significant differences were
      found in ESS scores and mean sleep latency of the MWT between groups. A high
      occurrence of REM SDB was found in mild (73.1%) and moderate cases (47.2%). While
      in the entire group and in non-REM SDB patients a strong male prevalence was
      found, the incidence of REM SDB was similar in men and women. CONCLUSION: Our
      results show that neither clinical history nor daytime sleepiness differentiate
      patients with REM SDB from non-REM SDB patients. The disorder is more common in
      mild and moderate cases; there is an equal incidence in women and men. These
      findings may suggest that REM-related SDB is a part of the spectrum of SDB.

PMID- 16304284
TI  - Association of asthma-related symptoms with snoring and apnea and effect on
      health-related quality of life.
AB  - OBJECTIVES: This study aimed to investigate the association of asthma-related
      symptoms with snoring and apnea, and to assess their effects on health-related
      quality of life (HRQL). DESIGN: Population-based cross-sectional study. SUBJECTS
      AND METHODS: A total of 10,224 parents and grandparents of students from 14
      randomly selected primary schools in city center were asked to answer
      questionnaires sent by their children. All subjects were questioned for asthma
      related symptoms, sleep-related disorders (snoring and apnea), and for HRQL using
      the Respiratory Questionnaire, Sleep and Health Questionnaire, and Short Form-12
      (SF-12) Health Survey, respectively. RESULTS: The overall response rate to
      questionnaires was 97.7%, and all analysis was performed on 7,469 subjects (3,920
      women and 3,549 men) who provided sufficient responses to questions. There were
      2,713 subjects who reported asthma-related symptoms. The snoring and the observed
      apnea were more prevalent in subjects with asthma-related symptoms (54.0% vs
      41.4%; odds ratio [OR], 1.7; 95% confidence interval [CI], 1.5 to 1.8; p < 0.001)
      than those without asthma-related symptoms (16.7% vs 7.0%; OR, 2.7; 95% CI, 2.3
      to 3.1; p < 0.001), respectively. Asthma-related symptoms were found to be
      associated with snoring (OR, 1.5; 95% CI, 1.3 to 1.6; p < 0.001) and observed
      apnea (OR, 2.2; 95% CI, 1.8 to 2.5; p < 0.001) after adjusting for gender, age,
      body mass index, income, education, and smoking. Also, HRQL was found to be
      adversely affected by asthma-related symptoms, snoring, and observed apnea (beta
      = - 0.26, p < 0.001; beta = - 0.07, p < 0.001; and beta = - 0.08, p < 0.001,
      respectively, for SF-12 overall score) after adjusting for other confounding
      factors. CONCLUSION: Present data suggest that there is a link between the sleep
      related breathing disorders and asthma-related symptoms. Moreover, the presence
      of snoring and observed apnea in individuals with asthma-related symptoms causes
      further impairment in HRQL. The effects on HRQL of coexistence of these three
      disorders should be supported by clinical studies.

PMID- 16304285
TI  - Identifying orthopedic patients at high risk for venous thromboembolism despite
      thromboprophylaxis.
AB  - OBJECTIVE: To evaluate risk factors for venous thromboembolism (VTE) despite
      thromboprophylaxis in major orthopedic surgery patients at a tertiary care
      hospital. METHODS: Charts from consecutive patients who underwent total hip
      replacement (THR), total knee replacement (TKR), or hip fracture surgery (HFS)
      [hip pinning or hemiarthroplasty] from August 1, 1999, to April 30, 2000, at a
      large Canadian teaching hospital were abstracted using standardized case report
      forms. Data were collected on patient characteristics, surgical characteristics,
      and thromboprophylaxis regimen. Results of tests performed for suspected VTE were
      documented. Associations between characteristics of interest and objectively
      confirmed VTE were examined in multivariate analysis. RESULTS: Over the study
      period, 310 patients underwent major orthopedic surgery and received standard
      thromboprophylaxis with either dalteparin or enoxaparin (mean duration of
      prophylaxis, 7 days). Of these, 34% underwent THR, 30% underwent TKR, and 36%
      underwent HFS. Of 83 suspected cases of VTE, 44 cases (7 proximal and 37 distal
      deep venous thrombosis [DVT]); 14% of study population) were confirmed with
      objective testing. Multivariate analyses revealed that knee surgery (odds ratio
      [OR], 4.8; 95% confidence interval [CI], 2.3 to 10.1) and type of low molecular
      weight heparin (LMWH) [enoxaparin (more protective): OR, 0.39; 95% CI, 0.20 to
      0.80] independently predicted VTE. No patient characteristics (including previous
      VTE, malignancy, hormonal therapy, postoperative complications) were associated
      with VTE. CONCLUSION: Despite standard thromboprophylaxis, symptomatic
      breakthrough VTE, primarily distal DVT, developed in 14% of patients undergoing
      major orthopedic surgery. Factors that independently predicted VTE in our
      population were TKR surgery and type of LMWH. TKR patients may warrant more
      aggressive postoperative physiotherapy and ambulation and adjunctive prophylactic
      measures such as pneumatic compression. Due to the heterogeneity of different
      LMWH compounds, direct comparison of the effectiveness of enoxaparin with
      dalteparin for orthopedic prophylaxis in prospective, randomized trials seems
      warranted.

PMID- 16304286
TI  - Delays in diagnosis of deep vein thrombosis and pulmonary embolism.
AB  - PURPOSES: To investigate delays in the diagnosis of deep vein thrombosis (DVT)
      and pulmonary embolism (PE). SUBJECTS AND METHODS: We prospectively identified
      1,152 patients in whom DVT or PE had been diagnosed at 70 North American medical
      centers. We recorded demographic characteristics and dates of symptom onset,
      initial medical evaluation, and confirmatory diagnostic tests. RESULTS: We
      identified substantial numbers of patients for whom there were delays in the
      diagnosis of DVT, PE, or both. For acute DVT, 170 of 808 patients (21%) received
      diagnoses > 1 week after symptom onset, and 40 of 808 patients (5%) received
      diagnoses > 3 weeks after symptom onset. On average, 80% of the delay in
      diagnosis of DVT occurred between symptom onset and medical evaluation. Acute PE
      was diagnosed in 59 of 344 patients (17%) > 1 week after symptom onset, and in 17
      of 344 patients (5%) > 3 weeks after the onset of symptoms. Delays in the
      diagnosis of PE represented both delays in seeking medical attention (mean, 3
      days; upper limit of 95% confidence interval [CI], 12 days); and delays from the
      first medical evaluation to diagnosis (mean, 2 days; upper limit of 95% CI, 9
      days). CONCLUSIONS: Although the majority of patients with DVT and PE seek
      medical attention and receive diagnoses promptly after symptom onset, substantial
      delays exist in the diagnosis of DVT and PE for many patients. There is a need to
      develop and test strategies that reduce delays in diagnosis.

PMID- 16304287
TI  - Assessing efficacy of high-frequency chest wall oscillation in patients with
      familial dysautonomia.
AB  - STUDY OBJECTIVE: To determine the benefits of daily use of high-frequency chest
      wall oscillation (HFCWO) in familial dysautonomia (FD) patients with lung
      disease. DESIGN: Pulmonary function tests, chest radiographs, and blood tests
      were performed on entry to the study. A retrospective chart review of 12 months
      prior to entry provided baseline data regarding respiratory illnesses,
      medications, doctor visits, hospitalizations, and absenteeism. Daily logs
      provided prospective data on these parameters as well as HFCWO usage. Evaluations
      were performed at 1, 3, 6, 9, and 12 months for pulse oximetry, spirometry, and
      log review. At the exit evaluation, blood tests and chest radiographs were
      repeated. PATIENTS: Fifteen FD patients with history of lung disease requiring
      daily inhalation therapy (7 female and 8 male; age range, 11 to 33 years) were
      enrolled in a 1-year clinical trial of HFCWO therapy. Two subjects withdrew after
      3 months and 6 months, respectively. Each individual served as his/her own
      control. RESULTS: Oxygen saturation improved by 1 month (median, 97.5%;
      interquartile range [IQR], 96 to 98%; vs median, 94%; IQR, 89 to 96%) and was
      sustained at exit evaluation (median, 98%; IQR, 98 to 98%) [p = 0.004]. Median
      FVC and peak expiratory flow rate (PEFR) were the pulmonary function measures
      with sustained improvement from baseline to exit (p = 0.02 and p = 0.03,
      respectively). When retrospective and prospective data were compared, all
      measured health outcomes improved significantly, including pneumonias (p =
      0.0156), hospitalizations (p = 0.0161), antibiotic courses (p = 0.0005),
      antibiotic days (p = 0.0002), doctor visits (p = 0.0005), and absenteeism (p =
      0.0002). CONCLUSION: In this limited study of FD patients, HFCWO effected
      significant improvements in all measured health outcomes and oxygen saturation;
      FVC and PEFR were the pulmonary function measures demonstrating sustained
      improvement.

PMID- 16304288
TI  - Prognostic significance of vascular endothelial growth factor, tumor necrosis,
      and mitotic activity index in malignant pleural mesothelioma.
AB  - OBJECTIVES: Tumor growth and metastasis are angiogenesis-dependent events, and
      several prognostic factors have been determined in malignant mesothelioma. In
      this study, we investigated the prognostic significance of vascular endothelial
      growth factor (VEGF), tumor necrosis (TN), and mitotic activity index (MAI) in
      malignant mesothelioma. For the first time (to our knowledge), we also
      demonstrated the association between VEGF staining, TN, and MAI in malignant
      mesothelioma. METHODS: Decortication and VATS materials of 40 patients were
      investigated. The routinely processed formalin-fixed, paraffin-embedded,
      hematoxylin-eosin-stained tumor sections that had been used for the original
      diagnostic purposes were retrieved. Hematoxylin-eosin sections were selected for
      VEGF immunostaining, TN, and mitotic count. Clinicopathologic data, stage of
      disease, and survival of patients were all determined. The correlations between
      variables were evaluated by Spearman rank correlation test. Both univariate
      analysis using the log-rank test and multivariate analysis using Cox regression
      model were performed for survival analysis. RESULTS: There was a significant
      correlation between VEGF staining and TN (r = 0.42, p = 0.006). In univariate
      analysis, both VEGF staining (p = 0.0002) and TN (p = 0.0055) showed significant
      correlation with short survival. Also, there was a positive correlation between
      VEGF and tumor stage (p = 0.046). In multivariate analysis, only VEGF was
      determined as an independent prognostic factor in malignant mesothelioma (p =
      0.001). There was no association between MAI and survival (p = 0.504).
      CONCLUSIONS: VEGF, known as an important angiogenic peptide, is an independent
      prognostic factor in malignant pleural mesothelioma. TN stimulates angiogenesis,
      and we observed a significant correlation between VEGF and TN. However, further
      studies are needed to evaluate the prognostic significance of angiogenic
      properties in malignant mesothelioma.

PMID- 16304289
TI  - High prevalence of estrogen and progesterone receptor expression in mediastinal
      cysts situated in the posterior mediastinum.
AB  - BACKGROUND: To identify and estimate the prevalence of mediastinal cysts lined by
      the epithelium expressing steroid receptors. METHODS: We retrieved 19 mediastinal
      cysts from our pathology files from 1996 to 2004, and examined estrogen receptor
      (ER) and progesterone receptor (PR) expressions in the cysts. RESULTS: Three
      paravertebral cysts, all in women, one bronchogenic cyst in a woman, nine thymic
      cysts, and six pericardial cysts were found in the pathology files. Paravertebral
      cysts were situated in the posterior mediastinum and were attached either to the
      left or the right of the vertebral column. All cysts were radiologically
      diagnosed before surgery as neurogenic tumors. They were excised by video
      assisted thoracoscopic surgery. The epithelial lining of the cyst in all three
      cases was strongly positive for both ER and PR. A thymic cyst in one woman was
      weakly positive only for the ER. In all other cases, the lining was entirely
      negative for both ER and PR. CONCLUSIONS: Posterior mediastinal paravertebral
      cysts characteristically express ER and PR. They should be recognized as a
      distinct type of mediastinal cyst because they are biologically different from
      bronchogenic cysts, seem not to be infrequent, and sometimes are misdiagnosed as
      a neurogenic tumor.

PMID- 16304290
TI  - Tracheomalacia and bronchomalacia in children: incidence and patient
      characteristics.
AB  - OBJECTIVE: Congenital airway malacia is one of the few causes of irreversible
      airways obstruction in children, but the incidence in the general population is
      unknown. Severe airway malacia or malacia associated with specific syndromes is
      usually recognized and diagnosed early in infancy, but information about clinical
      features of children with primary malacia, often diagnosed only later in
      childhood, is scarce. METHODS: We analyzed all flexible bronchoscopies performed
      between 1997 and 2004 in the Sophia Children's Hospital, summarized clinical
      features of children with primary airway malacia, estimated the incidence of
      primary airway malacia, and calculated the predictive value of a clinical
      diagnosis of airway malacia by pediatric pulmonologists. RESULTS: In a total of
      512 bronchoscopies, airway malacia was diagnosed in 160 children (94 males) at a
      median age of 4.0 years (range, 0 to 17 years). Airway malacia was classified as
      primary in 136 children and secondary in 24 children. The incidence of primary
      airway malacia was estimated to be at least 1 in 2,100. When pediatric
      pulmonologists expected to find airway malacia (based on symptoms, history, and
      lung function) prior to bronchoscopy, this was correct in 74% of the cases. In
      52% of the airway malacia diagnoses, the diagnosis was not suspected prior to
      bronchoscopy. Presenting clinical features of children with airway malacia were
      variable and atypical, showing considerable overlap with features of allergic
      asthma. Peak expiratory flow was more reduced than FEV(1). CONCLUSION: Primary
      airway malacia is not rare in the general population, with an estimated incidence
      of at least 1 in 2,100 children. Airway malacia is difficult to recognize based
      on clinical features that show overlap with those of more common pulmonary
      diseases. We recommend bronchoscopy in patients with impaired exercise tolerance,
      recurrent lower airways infection, and therapy-resistant, irreversible, and/or
      atypical asthma to rule out airway malacia.

PMID- 16304291
TI  - A randomized trial comparing the cardiac rhythm safety of moxifloxacin vs
      levofloxacin in elderly patients hospitalized with community-acquired pneumonia.
AB  - CONTEXT: Antimicrobial cardiac safety is of particular concern during the
      treatment of community-acquired pneumonia (CAP) in elderly patients, due to the
      presence of comorbid conditions and the use of multiple medications that may
      individually or synergistically affect cardiac repolarization. STUDY OBJECTIVE:
      To assess the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly
      patients hospitalized with CAP. DESIGN AND SETTING: Prospective, randomized,
      double-blind trial conducted at 47 hospitals in the United States. PATIENTS:
      Subjects > or = 65 years old with clinical signs/symptoms of CAP requiring
      initial parenteral therapy, including those with comorbidities. The safety
      population included 394 patients: 51.3% male; 85.3% white; mean age, 77.8 years.
      Two-thirds of the patients were > 75 years old, and 74.1% had a history of
      cardiac disease. INTERVENTIONS: Patients received IV/oral moxifloxacin (400 mg
      qd) or IV/oral levofloxacin (500 mg qd) for 7 to 14 days. Safety evaluations
      included 72 h of digital continuous 12-lead Holter monitoring, 12-lead ECGs at
      baseline and at maximum serum concentration on day 3, and adverse events. MAIN
      OUTCOME MEASURES: The primary safety end point was a composite of ventricular
      arrhythmia events based on Holter monitoring. RESULTS: Holter monitor data were
      available for 387 patients (192 receiving moxifloxacin and 195 receiving
      levofloxacin). Sixteen moxifloxacin-treated patients (8.3%) and 10 levofloxacin
      treated patients (5.1%) had a primary composite cardiac event (p = 0.29); most
      events were nonsustained ventricular tachycardia (VT) [14 patients receiving
      moxifloxacin, 7.3%; and 10 patients receiving levofloxacin, 5.1%]. One
      moxifloxacin-treated patient had sustained monomorphic VT (> 30 s), and one
      levofloxacin-treated patient had torsade de pointes. Mean +/- SD QTc (Fridericia
      formula) change on day 3 was + 6.4 +/- 23.2 ms for moxifloxacin and - 2.5 +/-
      22.9 ms for levofloxacin (p = 0.04). No deaths clearly related to study drugs
      occurred during the observation period. CONCLUSIONS: IV/oral moxifloxacin,
      although known to cause QTc interval prolongation, has a comparable cardiac
      rhythm safety profile to IV/oral levofloxacin in high-risk elderly patients with
      CAP.

PMID- 16304292
TI  - The severity of oxygen desaturation is predictive of carotid wall thickening and
      plaque occurrence.
AB  - STUDY OBJECTIVES: To characterize carotid intima-media thickness (IMT) and plaque
      occurrence in patients with newly diagnosed obstructive sleep apnea (OSA) without
      known cardiovascular disease. DESIGN: Prospective study. SETTING: Sleep
      Laboratory and Department of Cardiology of Grenoble University Hospital. PATIENTS
      AND INTERVENTION: OSA syndrome is associated with an increased cardiovascular
      risk. Carotid IMT is recognized as a marker of preclinic atheroma. A small number
      of studies have analyzed large-artery wall modifications in OSA syndrome. Eighty
      three patients (74 men; mean age +/- SD, 48 +/- 11 years; mean body mass index,
      27.4 +/- 4.2 kg/m(2)) were included. Mean respiratory disturbance index was 40.7
      +/- 19.2/h, mean nocturnal arterial oxygen saturation (Sao(2)) was 93.1 +/- 2.0%,
      and mean percentage of recording time spent at Sao(2) < 90% was 8.6 +/- 16.8%.
      Clinical BP was measured following European Society of Hypertension/European
      Society of Cardiology recommendations, and 24-h ambulatory BP monitoring was
      assessed. Ultrasonography was used to determine the carotid IMT and atheromatous
      plaque occurrence. MEASUREMENTS AND RESULTS: Twenty-five of 83 patients (30%) had
      carotid wall hypertrophy (IMT > 0.8 mm). In a logistic regression model, mean
      nocturnal Sao(2) < 92% (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.1
      to 12.7) was associated with carotid wall hypertrophy. ORs were even higher after
      adjustment for BP status (OR, 10.6; 95% CI, 1.6 to 50.9 in normotensive patients)
      and glucose levels (OR, 4.5; 95% CI, 1.0 to 20.9). Mean nocturnal Sao(2) < 92%
      and minimal nocturnal Sao(2) < 80% (ORs, 3.1 and 3.1; 95% CIs, 1.0 to 9.4 and 1.0
      to 8.5, respectively) were associated with the presence of carotid plaque
      formation independently of the BP status (hypertensive or normotensive).
      CONCLUSIONS: The severity of oxygen desaturation appears to be one of the best
      predictors for carotid IMT and plaque occurrence in OSA patients without known
      cardiovascular disease. Thus, carotid IMT and plaque formation appeared as early
      cardiovascular consequences in OSA patients.

PMID- 16304293
TI  - Bedside diagnosis and follow-up of patients with pleural effusion by a hand
      carried ultrasound device early after cardiac surgery.
AB  - OBJECTIVES: The aim of this study was to assess the potential value of hand
      carried ultrasound (HCU) devices in the diagnosis and follow-up of patients with
      pleural effusion (PE) after cardiac surgery. METHODS: Seventy consecutive
      patients were evaluated at bedside early after cardiac surgery, in the upright
      sitting position, using an HCU device on hospital admission and every 3 days
      until hospital discharge. The posterior chest wall was scanned along the
      paravertebral, scapular, and posterior axillary lines. For each hemithorax, an
      effusion index was derived as the sum of the intercostal spaces between the lower
      and upper limits of the PE along the lines of scanning, divided by 3. A standard
      chest radiograph was performed in all patients on hospital admission and at
      hospital discharge, and was qualitatively scored (0, absent; 1, small; 2, large
      PE). The findings of the HCU device and radiograph were compared using kappa
      statistics and the Kruskal-Wallis test. RESULTS: A chest ultrasound was feasible
      in all patients (mean [+/- SD] time, 5 +/- 2 min). Compared with the chest
      ultrasound, a physical examination showed a sensitivity of 69% and a specificity
      of 77%. On hospital admission, the HCU device detected a PE in 72 of 140
      hemithoraxes. Agreement with the finding of the radiograph was 76% (kappa =
      0.52). In 15 hemithoraxes, the HCU device revealed a PE that had not been
      diagnosed using the radiograph. Conversely, in 18 hemithoraxes a PE that had been
      diagnosed with a radiograph was not confirmed by the HCU device. The correlation
      between ultrasound and radiographic scores was statistically significant (p <
      0.001). At hospital discharge, a PE was present in 31 of 140 hemithoraxes
      according to the findings of the HCU device, and in 38 of 140 hemithoraxes
      according to the findings of the radiograph (agreement, 78%; kappa = 0.44).
      CONCLUSIONS: In patients early after cardiac surgery, HCU devices allow rapid PE
      detection and improve the clinical diagnosis. Compared to a radiograph, this
      method offers the unique advantage of the bedside evaluation of patients without
      the need for radiation exposure.

PMID- 16304295
TI  - Tissue Doppler-derived indices predict exercise capacity in patients with apical
      hypertrophic cardiomyopathy.
AB  - BACKGROUND: Although impaired left ventricular (LV) diastolic function is a
      prominent feature of hypertrophic cardiomyopathy (HCM), diastolic function and
      its relation to exercise capacity in apical HCM (ApHCM) has not been explored
      previously. This study was sought to determine the relationship between diastolic
      mitral annular velocities combined with conventional Doppler indexes and exercise
      capacity in patients with ApHCM. PATIENTS: Twenty-nine patients with ApHCM (24
      men; mean age +/- SD, 57 +/- 10 years) underwent supine bicycle exercise with
      simultaneous respiratory gas analysis and two-dimensional and Doppler
      echocardiographic study. RESULTS: The mitral inflow velocities (early filling
      [E], late filling, and deceleration time) were traced and measured. Early
      diastolic mitral annular velocity (E') was measured at the septal corner of
      mitral annulus by Doppler tissue imaging (DTI) from the apical four-chamber view.
      Pro-brain natriuretic peptide (proBNP) was measured at the time of
      echocardiography using a quantitative electrochemiluminescence immunoassay. E/E'
      ratio correlated inversely with maximal oxygen uptake (Vo(2)max) [r = - 0.47, p =
      0.0106]. There was a significant positive correlation between E' and Vo(2)max (r
      = 0.41, p = 0.024). However, no correlation was found between conventional two
      dimensional, Doppler indices, and proBNP and Vo(2)max). Of all the
      echocardiographic and clinical parameters assessed, E/E' ratio had the best
      correlation with exercise capacity (r - 0.47) and was the strongest independent
      predictor of Vo(2)max by multivariate analysis (p = 0.0106). CONCLUSIONS: DTI
      derived indexes (E', E/E' ratio), an estimate of myocardial relaxation and LV
      filling pressures, correlate with exercise capacity in patients with ApHCM,
      suggesting that abnormal diastolic function may be a factor limiting exercise
      capacity.

PMID- 16304294
TI  - Statin use is associated with a reduction in atrial fibrillation after noncardiac
      thoracic surgery independent of C-reactive protein.
AB  - STUDY OBJECTIVES: The level of C-reactive protein (CRP) has been shown to be
      elevated in patients with atrial fibrillation/flutter (AF) unrelated to surgery,
      and statins are known to lower the CRP level. To determine whether an elevated
      CRP level predisposes the patient to postoperative AF and whether statin use is
      associated with a reduced AF incidence, we studied a consecutive group of
      patients who were at risk for AF after undergoing thoracic surgery (age, > or =
      60 years). DESIGN AND SETTING: A prospective study in a tertiary care cancer
      center of 131 patients (mean [+/- SD] age, 73 +/- 6 years) who had undergone
      major lung or esophageal resection. High-sensitivity CRP and interleukin (IL)-6
      levels were measured before surgery, on arrival at the postanesthesia care unit,
      and on the first morning after surgery. Continuous telemetry was used for 72 to
      96 h to detect AF. RESULTS: AF occurred in 38 of 131 patients (29%) at a median
      time after surgery of 3 days. Although CRP and IL-6 levels increased
      significantly (p < 0.001) in response to surgery, patients with or without AF did
      not differ in perioperative values. In a stepwise logistic regression, statin use
      was associated with a threefold decrease in the odds of developing AF (odds ratio
      [OR], 0.26; 95% confidence interval [CI], 0.08 to 0.82; p = 0.022) and a greater
      PR interval (OR, 1.11 per 5-ms increments; 95% CI, 1.01 to 1.22; p = 0.027)
      predicted an increase in the risk of AF. CONCLUSIONS: The preoperative use of
      statins was associated with a protective effect against postoperative AF
      independent of CRP levels. In contrast to AF in the general population, early
      markers of inflammation did not predict the postoperative occurrence of AF.

PMID- 16304296
TI  - Ventilation and exercise performance after phrenic nerve and multiple intercostal
      nerve transfers for avulsed brachial plexus injury.
AB  - BACKGROUND: Diaphragmatic excursion, lung function, exercise performance, and
      clinical symptoms have not been previously described in patients after phrenic
      nerve transfer (PNT) and/or multiple intercostal nerve transfer (MIT) for the
      repair of avulsed brachial plexus injury (ABPI) to prevent functional
      musculoskeletal impairment in the shoulder. SETTING: A university-based hospital.
      METHODS: Dyspnea scores, chest ultrasonography to assess diaphragmatic excursion,
      and pulmonary function testing were performed to assess ventilation in patients
      sustaining trauma to their brachial plexus. In addition, cardiopulmonary exercise
      testing was also performed. These studies were obtained prior to surgical
      intervention, and were repeated postoperatively at 6, 12, 18, 24, and 36 months.
      The results obtained preoperatively were compared to those obtained throughout
      the postoperative monitoring period. RESULTS: This study demonstrates that the
      PNT-MIT procedure results in permanent ipsilateral diaphragmatic paralysis
      accompanied by an approximately 8% decrease in inspiratory capacity, FVC, and
      total lung capacity. There was also an 11% increase in diffusing capacity noted
      during the period between 6 months and 3 years after PNT-MIT procedure. Despite
      these measurable changes in lung function, the patients reported amelioration of
      their dyspnea complaint within 6 months of undergoing this procedure, which was
      due mainly to an improvement in their cardiovascular exercise performance related
      to increased daily activity. CONCLUSIONS: This study demonstrates that the PNT
      MIT procedure is a safe method for the restoration of drop shoulder incurred by
      ABPI. This surgery has an impact on measurable diaphragmatic and lung function
      but with minimal impact in terms of postoperative clinical symptoms and exercise
      performance.

PMID- 16304297
TI  - Evaluation of the causes for racial disparity in surgical treatment of early
      stage lung cancer.
AB  - STUDY OBJECTIVES: Black patients undergo surgical treatment for early stage lung
      cancer less often than whites. We wanted to determine the causes for the racial
      difference in resection rates. DESIGN: We studied a retrospective cohort of
      patients who presented to our institution with potentially resectable lung cancer
      (stage I or II) between the years 1995 and 1998, inclusive. SETTING: A tertiary
      referral hospital and clinic with a cancer database of all lung cancer patients
      seen. PATIENTS: A total of 281 patients were included: 97 black patients (35%)
      and 184 white patients (65%). MEASUREMENTS AND RESULTS: The surgical rate was
      significantly lower in blacks than in whites (56 of 97 patients [58%] vs 137 of
      184 patients [74%], p = 0.004). We could not find evidence that the rate at which
      surgical treatment was offered was different between the two racial groups (68 of
      97 black patients [70%] and 145 of 184 white patients [79%], p = 0.11). After
      controlling for preoperative pulmonary function, tumor stage, history of smoking,
      and significant comorbidities, we were unable to show that race was a predictor
      of being offered surgical treatment (odds ratio, 0.46; 95% confidence interval,
      0.18 to 1.14; p = 0.09). The difference in surgical rates was mainly due to the
      fact that blacks were found to decline surgical treatment more often than their
      white counterparts (12 of 68 patients [18%] vs 7 of 145 patients [5%], p =
      0.002). CONCLUSIONS: Our analysis suggests that the lower surgical rate among
      black patients with early stage lung cancer is mainly due to low rates of
      acceptance of surgical treatment.

PMID- 16304298
TI  - Effect of modified ultrafiltration on pulmonary function after cardiopulmonary
      bypass.
AB  - BACKGROUND: Pulmonary dysfunction is one of the most common manifestations of
      inflammatory response after cardiopulmonary bypass (CPB). OBJECTIVE: This
      prospective randomized study was conducted to evaluate the effect of a modified
      ultrafiltration (MUF) technique on pulmonary function after CPB in children.
      METHODS: Forty patients weighing from 5 to 10 kg with congenital heart disease
      who required CPB for primary biventricular operative repair were prospectively
      randomized into two groups. The control group received conventional
      ultrafiltration (CUF) during CPB, and the study group received CUF and MUF.
      Pulmonary compliance (static and dynamic) and gas exchange capacity of the lung
      expressed as oxygen index, respiratory index, ventilation index, and alveolar
      arterial oxygen pressure difference were measured after intubation (baseline), at
      the termination of CPB, at the end of MUF, on admission to the ICU, and 6 h
      postoperatively. RESULTS: There was no significant difference in lung compliance
      and gas exchange between the two groups before CPB. CPB produced a significant
      decrease in static and dynamic lung compliance in both groups. In the control
      group, static and dynamic lung compliance decreased from 1.0 +/- 0.3 to 0.90 +/-
      0.3 mL/cm/kg and 0.87 +/- 0.2 to 0.71 +/- 0.1 mL/cm/kg (+/- SE) [p = 0.0002 and p
      = 0.002, respectively]. In the study group, static and dynamic lung compliance
      decreased from 1.0 +/- 0.2 to 0.89 +/- 0.03 mL/cm/kg and 0.94 +/- 0.2 to 0.77 +/-
      0.1 mL/cm/kg (p = 0.002 and p = 0.002, respectively). There was no significant
      difference in the decrease in static (p = 0.9) or dynamic lung compliance (p =
      0.3) between the two groups. MUF produced a significant immediate improvement in
      both static lung compliance (0.89 +/- 0.2 to 0.98 +/- 0.2 mL/cm/kg, p = 0.03) and
      dynamic lung compliance (0.77 +/- 0.1 to 0.93 +/- 0.2 mL/cm/kg, p = 0.007). The
      same was observed regarding the gas exchange capacity. CPB produced a significant
      decrease in lung gas exchange capacity, and MUF produced a significant immediate
      improvement in lung gas exchange capacity. The effect of MUF on lung compliance
      and gas exchange capacity was not sustained after admission to the ICU nor 6 h
      later postoperatively. There was no significant difference in the time of
      extubation between the two groups (12 +/- 3 h and 13 +/- 2 h, p = 0.4), the
      length of ICU stay, or the total hospital stay postoperatively. CONCLUSIONS: The
      use of MUF after CPB can produce an immediate improvement in lung compliance and
      gas exchange capacity, which may effectively minimize pulmonary dysfunction
      postbiventricular repair of congenital heart disease. However, these improvements
      are not sustained for the first 6 h postoperatively and do not reduce the
      duration of postoperative intubation, ICU stay, or total hospital stay.

PMID- 16304299
TI  - Video-assisted thoracic surgery thymectomy for nonthymomatous myasthenia gravis.
AB  - STUDY OBJECTIVES: Minimal-access thymectomy has become increasingly popular as
      surgical treatment for patients with nonthymomatous myasthenia gravis (NTMG)
      because of its comparable efficacy, safety, and lesser degree of tissue trauma
      compared with conventional open surgery. We reviewed and analyzed our data on
      video-assisted thoracic surgery (VATS) thymectomy and present the clinical
      outcomes according to the Myasthenia Gravis Foundation of America classification.
      DESIGN: A retrospective review of VATS thymectomy for NTMG in a university
      hospital over a 12-year period. Data were collected from the medical records and
      supplemented with telephone surveys. The impact of surgery and other variables
      potentially affecting complete stable remission (CSR) were calculated using
      Kaplan-Meier survival curves; comparisons between survival curves was performed
      using the log-rank test. RESULTS: A total of 38 consecutive patients underwent
      VATS thymectomy for NTMG. Median postoperative stay was 3 days. Pathologic
      examination revealed thymic hyperplasia in 61.1% of cases, normal thymus in
      22.2%, and thymic atrophy in 16.6%. There was no perioperative mortality;
      complications occurred in four patients. After a median follow-up of 69 months,
      91.6% of patients experienced improvement, with crude CSR achieved in 22.2%.
      Kaplan-Meier survival curve demonstrated a 75% CSR rate at 10-year follow-up. On
      univariate analysis, only disease duration < or = 12 months (p = 0.03) was
      associated with a statistically significant improvement in CSR. CONCLUSIONS: VATS
      thymectomy for NTMG results in symptomatic improvement in the vast majority of
      patients, with a high rate of CSR. The procedure is associated with low morbidity
      and no perioperative mortality. Future studies on thymectomy for myasthenia
      gravis should be reported in a standardized manner to allow accurate comparisons
      between results in the absence of randomized prospective trials.

PMID- 16304300
TI  - Perioperative risk factors for anastomotic leakage after esophagectomy: influence
      of thoracic epidural analgesia.
AB  - STUDY OBJECTIVES: Anastomotic leakage after esophagectomy is associated with high
      postoperative morbidity and mortality. The most important predisposing factors
      for anastomotic leaks are ischemia of the gastric conduit and low blood oxygen
      content. The aim of this study was to evaluate the influence of thoracic epidural
      analgesia (TEA) on the incidence of anastomotic leakage after esophagectomy.
      DESIGN: Retrospective study. SETTING: A thoracic surgery and anesthesia
      department in a teaching hospital. PATIENTS: Two hundred seven patients who
      underwent one-stage esophagectomy between 1998 and 2003. INTERVENTIONS: The
      effects of perioperative factors and postoperative complications on the incidence
      of anastomotic leakage were analyzed. Leakage was defined as an anastomotic
      disruption detected by an ionic x-ray contrast study and confirmed by upper
      endoscopy in the postoperative period. Analyzed factors included effective TEA
      placed before the surgical procedure. MEASUREMENTS AND RESULTS: Anastomotic
      leakage occurred in 23 patients (11%). This complication was associated with a
      significant increase in length of stay in the ICU and in the hospital (mean, 19
      +/- 16 days vs 9 +/- 7 days [+/- SD], p = 0.008; and 43 +/- 27 days vs 23 +/- 11
      days, respectively; p < 0.001). Mortality in patients presenting anastomotic
      leakage was 26%, compared with 5.4% in the remainder (p = 0.002). Factors
      independently associated with the incidence of leakage included estimated blood
      loss per milliliter during the surgical procedure (odds ratio [OR], 1.004; 95%
      confidence interval [CI], 1.001 to 1.007), the cervical location for anastomosis
      (OR, 5.4; 95% CI, 1.3 to 22.9), and the development of an ARDS in the
      postoperative period (OR, 4.1; 95% CI, 2.6 to 176.5). Ninety-three patients
      benefited from an effective TEA for 4.4 +/- 0.8 days. The use of TEA was
      independently associated with a decrease in the incidence of anastomotic leakage
      (OR, 0.13; 95% CI, 0.02 to 0.71). CONCLUSIONS: The results of this retrospective
      study suggest that TEA is associated with a decrease in occurrence of anastomotic
      leakage.

PMID- 16304301
TI  - Phase II study of neoadjuvant chemotherapy with gemcitabine and vinorelbine in
      resectable non-small cell lung cancer.
AB  - OBJECTIVE: We assessed the efficacy of a non-platinum-containing doublet
      chemotherapy of gemcitabine and vinorelbine as induction therapy prior to
      surgical resection in patients with stage IB-IIIA and selected stage IIIB non
      small cell lung cancer (NSCLC). The primary clinical end point was radiographic
      disease response rate, and the secondary end points were pathologic response
      rate, treatment-related toxicity, surgical resectability and outcome, and overall
      and disease-free survival. METHODS: Patients underwent staging with CT of the
      chest and upper-abdomen, whole-body F-18 fluorodeoxyglucose positron emission
      tomography, bronchoscopy, and mediastinoscopy. The patients had to have medically
      and surgically resectable disease. Chemotherapy consisted of gemcitabine, 1,000
      mg/m(2), and vinorelbine, 25 mg/m(2), administered on days 1, 8, 22, and 29.
      Imaging studies were repeated between days 43 and 50. Disease response was
      assessed by response evaluation criteria in solid tumors, and patients with
      resectable disease were offered surgery between days 50 and 70. Patients were
      followed up every 3 months for 2 years with chest CT. RESULTS: Between January
      2000 and March 2004, 27 patients with stage IB NSCLC, 15 patients with stage II
      NSCLC, and 20 patients with stage III NSCLC were entered. After induction
      chemotherapy 34% (95% confidence interval [CI], 23 to 48%) had an objective
      radiographic response, 2% had a complete pathologic response, 90% underwent
      thoracotomy, and 77% underwent a complete resection. There were four deaths in
      the 6-week period following surgery, and there were no deaths related to
      chemotherapy. There were no unexpected morbidities from surgery or chemotherapy.
      The 1-year and 2-year overall survival rates were 80% (95% CI, 68 to 88%) and 65%
      (95% CI, 50 to 76%), and the median overall survival was 38.2 months.
      CONCLUSIONS: Induction chemotherapy with gemcitabine and vinorelbine results in 1
      year and 2-year survival rates and a median survival time comparable to those
      obtained with platinum-containing doublets. However, it appears to be less
      efficacious in terms of radiographic and pathologic response rates compared with
      platinum-containing chemotherapy doublets.

PMID- 16304302
TI  - The place of patient satisfaction in quality assessment of lung cancer thoracic
      surgery.
AB  - STUDY OBJECTIVES: To compare the quality of non-small cell lung cancer (NSCLC)
      surgical care with patient satisfaction. DESIGN: Prospective study. SETTING:
      Academic hospital departments of thoracic oncology and surgery. PATIENTS AND
      METHODS: Patients presenting with recently diagnosed NSCLC and eligible for front
      line thoracic surgery were eligible. Patient satisfaction was assessed using the
      Questionnaire of Satisfaction of Hospitalized Patients. Quality of surgical care
      was evaluated using an original score built accordingly to British Thoracic
      Society guidelines. Univariate analysis used parametric (Pearson correlation, t
      test) and nonparametric tests (Mann-Whitney U test) according to test conditions.
      Probability of survival was estimated using the Kaplan-Meier method. RESULTS:
      Seventy patients (mean age, 63.7 years) were included. Lobectomy was performed in
      62 cases, and pneumonectomy was performed in 8 cases. In all, 28 patients had a
      postoperative complication. One-year survival rates for patients with stage I-II
      and stage IIIA NSCLC were 84% and 58%, respectively. Mean patient satisfaction
      was 78 +/- 13/100 and 69 +/- 13/100 for global staff and structure index,
      respectively (+/- SD). Mean score for quality of surgical care was 88.7/100
      (range, 51 to 100). The absence of postoperative complication was significantly
      related to a high level of satisfaction regarding the structure (r = 0.30, p <
      0.05). Other features of patient satisfaction did not show a significant
      correlation with the quality of the preoperative selection process or the
      surgical procedure itself (r < 0.20). CONCLUSIONS: Considering the lack of
      significant correlation, the present study does not support a shortcut between
      quality of care and patient satisfaction. Nonetheless, patient satisfaction
      should be integrated into rather than substituted for the quality of health-care
      assessment, which also needs further development.

PMID- 16304303
TI  - Deep-breathing exercises reduce atelectasis and improve pulmonary function after
      coronary artery bypass surgery.
AB  - STUDY OBJECTIVES: To investigate the effects of deep-breathing exercises on
      pulmonary function, atelectasis, and arterial blood gas levels after coronary
      artery bypass graft (CABG) surgery. DESIGN, SETTING, AND PATIENTS: In a
      prospective, randomized trial, patients performing deep-breathing exercises (n =
      48) were compared to a control group (n = 42) who performed no breathing
      exercises postoperatively. Patient management was similar in the groups in terms
      of assessment, positioning, and mobility. INTERVENTIONS: The patients in the deep
      breathing group were instructed to perform breathing exercises hourly during
      daytime for the first 4 postoperative days. The exercises consisted of 30 slow,
      deep breaths performed with a positive expiratory pressure blow-bottle device (+
      10 cm H(2)O). MEASUREMENTS AND RESULTS: Spirometric measurements, spiral CT
      (three transverse levels), arterial blood gas analysis, and scoring of subjective
      experience of the breathing exercises were performed on the fourth postoperative
      day. Atelectasis was only half the size in the deep-breathing group compared to
      the control group, amounting to 2.6 +/- 2.2% vs 4.7 +/- 5.7% (p = 0.045) at the
      basal level and 0.1 +/- 0.2% vs 0.3 +/- 0.5% (mean +/- SD) [p = 0.01] at the
      apical level. Compared to the control subjects, the patients in the deep
      breathing group had a significantly smaller reduction in FVC (to 71 +/- 12%, vs
      64 +/- 13% of the preoperative values; p = 0.01) and FEV(1) (to 71 +/- 11%, vs 65
      +/- 13% of the preoperative values; p = 0.01). Arterial oxygen tension, carbon
      dioxide tension, fever, or length of ICU or hospital stay did not differ between
      the groups. In the deep-breathing group, 72% of the patients experienced a
      subjective benefit from the exercises. CONCLUSIONS: Patients performing deep
      breathing exercises after CABG surgery had significantly smaller atelectatic
      areas and better pulmonary function on the fourth postoperative day compared to a
      control group performing no exercises.

PMID- 16304304
TI  - Comparison of lung volume reduction surgery and physical training on health
      status and physiologic outcomes: a randomized controlled clinical trial.
AB  - STUDY OBJECTIVES: In 1996, researchers in Sweden initiated a collaborative
      randomized study comparing lung volume reduction surgery (LVRS) and physical
      training with physical training alone. The primary end point was health status;
      secondary end points included survival and physiologic measurements. DESIGN:
      After an initial 6-week physical training program, researchers' patients were
      randomized to either LVRS (surgical group [SG]) with continued training for 3
      months, or to continued training alone (training group [TG]) for 1 year. SETTING:
      All seven thoracic surgery centers in Sweden. PATIENTS: All patients in Sweden
      with severe emphysema fulfilling inclusion criteria for LVRS. INTERVENTIONS:
      Patients randomized to surgery underwent a median sternotomy, except for a few
      patients in whom thoracotomy or video-assisted thoracoscopy were performed. In
      the TG, supervised physical training continued for 1 year; in the SG, supervised
      physical training continued for 3 months postoperatively. MEASUREMENTS AND
      RESULTS: Fifty-three patients were included in each group. Six in-hospital deaths
      occurred after surgery (12%), and one more death occurred during follow-up. Two
      deaths occurred in the TG. The difference in death rates between the groups was
      not statistically significant. Health status, as measured by St. George
      Respiratory Questionnaire (SGRQ) [total scale score mean difference at 1 year,
      14.7; 95% confidence interval (CI), 9.8 to 19.7] as well as by the Medical
      Outcomes Study Short-Form General Health Survey (physical function scale score
      mean difference at 1 year, 19.7; 95% CI, 12.1 to 27.3) was improved from baseline
      in the SG compared with the TG. FEV(1), residual volume, and shuttle walking test
      values also improved in the SG but not in the TG after 6 months and 12 months.
      CONCLUSIONS: In severe emphysema, LVRS can improve health status in survivors but
      is associated with mortality risk. The effects are stable for at least 1 year.
      Physical training alone failed to achieve a similar improvement.

PMID- 16304305
TI  - Role of quantitative CT in predicting hypoxemia and complications after lung
      lobectomy for cancer, with special reference to area of emphysema.
AB  - STUDY OBJECTIVES: To determine the ability of quantitative CT, with special
      reference to area of emphysema, to predict early postoperative oxygenation
      capacity and outcome after lung lobectomy for cancer. METHODS: Sixty-two
      consecutive patients scheduled to undergo lung lobectomy for cancer were enrolled
      in this study. The area of emphysema (< - 910 Hounsfield units) was measured on a
      three-dimensional CT lung model. Arterial oxygen saturation (Sao(2)) was
      calculated from Pao(2) measured 1 day before and 1 day after surgery with
      patients at rest breathing room air. A patient was considered to have recovered
      at the completion of a standardized management regimen. RESULTS: Postoperative
      Sao(2) (postSao(2)) was predicted by the baseline value and the area of emphysema
      with the use of a regression equation. Ten of the 62 patients (16%) had
      postoperative cardiopulmonary complications (CPCs). The median time to
      postoperative recovery was 3 days (range, 1 to 17 days). Predicted postSao(2) and
      predicted postoperative FEV(1) were shown to be significant independent
      predictors of postoperative CPCs as well as postoperative recovery time.
      CONCLUSION: Determining the area of emphysema by quantitative CT is useful in
      predicting early postoperative oxygenation capacity. Predicted oxygenation
      capacity and predicted ventilatory capacity independently affect perioperative
      outcomes. Therefore, using quantitative CT in combination with spirometry may
      improve risk prediction in patients undergoing lung lobectomy for cancer.
      However, the role of quantitative CT in grading nonemphysematous lung diseases,
      such as interstitial lung diseases, must be investigated.

PMID- 16304306
TI  - Radiofrequency ablation of primary lung cancer: results from an ablate and resect
      pilot study.
AB  - STUDY OBJECTIVES: The role of radiofrequency ablation (RFA) for primary lung
      cancer remains poorly defined. The purpose of this "ablate and resect" pilot
      study was to evaluate the safety of performing RFA in patients with primary non
      small cell lung cancer (NSCLC) and to characterize the histologic changes in
      tumor tissue following such ablation. DESIGN: This prospective study was
      undertaken at a single institution, and 10 patients were accrued from June 2002
      to June 2003. Eligible patients included those with clinical stage I or II
      disease. RFA of the tumor was performed through a standard thoracotomy followed
      by conventional lobectomy and lymph node dissection. Extent of cell death was
      determined histologically. MEASUREMENTS AND RESULTS: Following the exclusion of
      two patients, the treated portions of eight tumors were examined for tumor cell
      viability. Gross inspection and routine histologic staining could not reliably
      identify the "immediately ablated" tissue. However, using a supravital staining
      technique, the treated areas from seven of the eight tumors (87.5%) demonstrated
      > 80% nonviability (100% nonviability was noted in the treated areas from three
      of the eight tumors). No bleeding or thermal complications were noted at the time
      of RFA, and none of the patients had skin burns at the electrode dispersive pad
      sites. CONCLUSIONS: RFA of primary NSCLC is feasible and can be performed safely
      in the setting of an open thoracotomy. Complete tumor cell necrosis, as
      determined by supravital staining, was noted in the treated areas from three of
      eight tumors (37.5%). Such complete ablation was observed in the treated areas
      from smaller tumors (< 2 cm), whereas the treated areas from larger tumors
      demonstrated incomplete ablation. Additional investigation with histopathologic
      correlation is needed to fully assess the long-term efficacy of RFA for NSCLC.

PMID- 16304307
TI  - Does preoperative transbronchial biopsy worsen the postsurgical prognosis of lung
      cancer? A propensity score-adjusted analysis.
AB  - STUDY OBJECTIVES: Our aim was to clarify the hypothesis that the postsurgical
      prognosis of patients with non-small cell lung cancer (NSCLC) proven by
      preoperative diagnostic transbronchial biopsy (TBLB) was worse than that of the
      patients with NSCLC determined at the time of surgery. DESIGN: We entered the
      propensity score as a continuous variable in the Cox proportional hazards model,
      along with the success/failure of TBLB and other covariates that were adjusted
      for the bias inherent to the success/failure of the TBLB examination. PATIENTS:
      Five hundred ninety-nine consecutive patients with NSCLC undergoing complete
      resection were divided into two groups. Pathologic diagnosis by TBLB was
      preoperatively determined in patients belonging to group 1 (n = 367). TBLB was
      unsuccessful and exploratory thoracotomy or thoracoscopy was followed by surgical
      resection in patients belonging to group 2 (n = 232). The overall recurrence-free
      survival rate was examined as the surgical outcomes. RESULTS: The postsurgical
      recurrence-free rate was significantly higher in group 2 than in group 1. Group 2
      patients showed better prognosis than group 1 patients, even when the data
      between the two groups were adjusted by propensity score. When the groups were
      subdivided by the pathologic stage of disease, the subgroup consisting of group 2
      patients with stage IA and IB lung cancer still showed a higher recurrence-free
      rate than those in group 1 by propensity score analysis. CONCLUSIONS: The
      postsurgical prognosis of the patients with NSCLC was significantly better if the
      preoperative TBLB was unsuccessful. This result suggested that advanced NSCLC had
      a tendency to be diagnosed with TBLB and, possibly, that the TBLB procedure might
      worsen the prognosis of patients with resectable NSCLC. We suggest that
      intraoperative diagnosis followed by the consecutive resection of NSCLC may be
      beneficial for improving the surgical outcomes of NSCLC patients.

PMID- 16304308
TI  - Risk stratification for lung cancer surgery: impact of induction therapy and
      extended resection.
AB  - STUDY OBJECTIVES: Current surgical strategies for lung cancer are directed toward
      the following two distinct targets: the increased prevalence of early-stage lung
      cancer; and locally advanced lung cancer treated with induction therapy (IT). To
      establish the risk stratification for operative morbidity from this viewpoint, we
      evaluated the impact of IT and/or an extended surgical procedure on operative
      results. DESIGN: Retrospective study. SETTING: A 674-bed teaching hospital.
      PATIENTS AND METHODS: The morbidity and mortality of 758 consecutive patients who
      underwent surgery for the treatment of non-small cell lung cancer were analyzed.
      There were 666 patients who underwent surgery alone (S group; 560 standard
      lobectomies and 106 extended resections) and 92 patients who received IT (IT
      group; 35 standard lobectomies and 57 extended resections). Comparisons between
      the groups were performed using unpaired t tests or chi(2) tests. Univariate and
      multivariate logistic regression analyses were used to determine the risk factors
      for operative morbidity and mortality. RESULTS: IT and extended surgery were
      strong independent factors for predicting postoperative morbidity (p < 0.0001).
      Significant differences were observed for pathologic stage (p < 0.0001),
      preoperative hemoglobin and Dlco levels (p < 0.001), the ratio of extended
      resection (p < 0.0001), and operation time and intraoperative bleeding (p <
      0.001) between the S and IT groups. The overall morbidity and mortality rates
      were 16.8% and 0.9%, respectively, in the S group, and 55.4% and 5.4%,
      respectively, in the IT group (p < 0.01). The overall morbidity and mortality
      rates were 63.2% and 7.0%, respectively, for extended resection after IT, and
      12.8% and 0.3%, respectively, for those who underwent a standard resection
      without IT. CONCLUSIONS: The morbidity and mortality of lung resection are both
      significantly increased after IT, and the patients with the greatest risk are
      those who have undergone IT and extended resection. The impact of IT on risk
      stratification should be emphasized in perioperative care.

PMID- 16304309
TI  - Prognostic value of preoperative cardiac troponin I in patients with non-ST
      segment elevation acute coronary syndromes undergoing coronary artery bypass
      surgery.
AB  - STUDY OBJECTIVES: Elevated levels of cardiac troponin I (cTnI) have been
      associated with adverse short-term and long-term outcomes in acute coronary
      syndrome (ACS) patients and in patients who underwent coronary artery bypass
      grafting (CABG); however, the prognostic implications of preoperative cTnI
      determination have not been investigated so far. DESIGN AND SETTING:
      Retrospective study in a department of cardiothoracic surgery of a university
      hospital. PATIENTS AND METHODS: A possible correlation between preoperative cTnI
      levels and major adverse cardiac events (MACE) and in-hospital mortality in CABG
      patients with non-ST-segment elevation ACS (NSTE-ACS) was investigated. cTnI was
      determined in 1,978 of 3,124 consecutive CABG patients. Among these, 1,592
      patients had preoperative cTnI levels < 0.1 ng/mL and therefore served as control
      subjects (group 1), 265 patients had NSTE-ACS with cTnI levels from 0.11 to 1.5
      ng/mL (group 2), and 121 patients had NSTE-ACS with cTnI levels > 1.5 ng/mL
      (group 3). cTnI levels, clinical data, MACE, and in-hospital mortality were
      recorded prospectively. Logistic regression and receiver operating characteristic
      analyses were applied to determine prognostic cutoff values of cTnI. RESULTS:
      Perioperative myocardial infarction was found in 5.8% of the patients in group 1,
      8.3% of the patients in group 2 (odds ratio [OR], 1.5; 95% confidence interval
      [CI], 0.9 to 2.5), and 18.2% patients in group 3 (OR, 3.6; 95% CI, 2.1 to 6.2; p
      < 0.0001, Cochran-Armitage trend test). Low cardiac output syndrome occurred in
      1.5% of patients in group 1, 4.2% of patients in group 2 (OR, 2.8; 95% CI, 1.3 to
      6.1), and 10.9% patients in group 3 (OR, 6.5; 95% CI, 2.9 to 14.4; p < 0.0001).
      In-hospital mortality was 1.5% in group 1, 3.0% in group 2 (OR, 2.0; 95% CI, 0.8
      to 4.8), but 6.6% in group 3 (OR, 4.6; 95% CI, 1.9 to 11.1; p < 0.0001).
      Univariate and multivariate logistic regression analyses identified cTnI as the
      strongest preoperative predictor for MACE and in-hospital mortality,
      respectively. CONCLUSIONS: Preoperative cTnI measurement before CABG appears as a
      powerful and independent determinant of short-term surgical risk in patients with
      NSTE-ACS.

PMID- 16304310
TI  - Effects of inhaled nitric oxide administration on early postoperative mortality
      in patients operated for correction of atrioventricular canal defects.
AB  - OBJECTIVE: Postoperative pulmonary hypertension (POPH) substantially increases
      mortality after repair of congenital heart diseases. Inhaled nitric oxide (NO)
      has been reported as an effective and specific means of controlling POPH crisis.
      No randomized, placebo-controlled study has addressed the ability of NO
      administration to reduce mortality. Such a trial could raise ethical questions.
      DESIGN: Observational study with historical control subjects based on
      multivariate confounder scores. SETTING: Surgical pediatric ICU in a university
      hospital. PATIENTS: Two hundred ninety-four records of patients operated on for
      atrioventricular (AV) canal between 1984 and 1994 who presented with severe POPH.
      INTERVENTIONS: All variables found to be predictive for death by univariate tests
      were entered in a multivariate forward stepwise logistic regression model. Two
      paired groups regarding risk factors for death and only differing for POPH
      treatment (NO or conventional treatment) were constructed on the basis of
      predicted values obtained from this model. Twenty-five patients received NO, and
      39 control patients, operated on between 1984 and 1994, received conventional
      treatment for POPH. MEASUREMENTS AND RESULTS: Postoperative pulmonary pressure,
      date of operation, and occurrence of an infectious complication were retained in
      the model. The comparison between the two paired groups showed a significant
      difference in mortality (24%; 95% confidence interval [CI], 7 to 41%; vs 56%; 95%
      CI, 37 to 75%, respectively; p = 0.02). CONCLUSIONS: This study suggests that
      there is a high probability for postoperative mortality reduction associated with
      administration of inhaled NO when severe POPH occurs in children operated for
      complete repair of AV canal.

PMID- 16304311
TI  - Accuracy of virtual bronchoscopy for grading tracheobronchial stenosis:
      correlation with pulmonary function test and fiberoptic bronchoscopy.
AB  - STUDY OBJECTIVES: To compare the accuracy of virtual bronchoscopy (VB) with
      fiberoptic bronchoscopy (FOB) and pulmonary function testing (PFT) for the
      assessment of tracheal stenosis and bronchial anastomotic stenosis. DESIGN:
      Prospective case series. SETTING: Pulmonary institute of major tertiary
      university-affiliated center. PATIENTS: The study group included 10 lung
      transplant recipients and 13 patients with central airway stenosis.
      INTERVENTIONS: All patients underwent PFT, VB, and FOB. All cases were graded by
      each modality on a scale of 1 to 3, and the findings were compared between
      modalities. RESULTS: Mean +/- SD stenosis score was 2.0 +/- 0.79 for PFT, 1.62 +/
      0.73 for FOB, and 1.82 +/- 0.77 for VB. A statistically significant correlation
      was found between VB and FOB scores (p < 0.0001, r = 0.76) and between VB scores
      and PFT (p = 0.03, r = 0.45). There was no correlation between PFT and FOB.
      CONCLUSIONS: VB grading of tracheobronchial stenosis is well correlated with PFT.
      VB may be used to evaluate patients with known tracheobronchial stenosis after
      treatment and thereby reduce the frequency of repeated invasive FOB performed for
      that purpose. The correlation of VB with PFT may improve the reliability of this
      approach.

PMID- 16304312
TI  - Endobronchial ultrasound-driven biopsy in the diagnosis of peripheral lung
      lesions.
AB  - STUDY OBJECTIVES: The aim of our study was to compare the diagnostic yield of two
      bronchoscopic procedures: endobronchial ultrasound-driven transbronchial biopsy
      (EBUS-TBB) and transbronchial biopsy (TBB) in peripheral pulmonary lesions.
      DESIGN: Prospective, randomized, blinded study. SETTING: University Hospital of
      Rome, Italy. PATIENTS AND METHODS: We examined 799 patients with peripheral lung
      lesions using bronchoscopy. Patients who could undergo a complete clinical
      diagnostic follow-up (n = 293) were enrolled in the study and randomly assigned
      to EBUS-TBB or TBB. We performed these two procedures on 221 patients (97 EBUS
      TBB and 124 TBB). Patients in whom biopsies were not diagnostic underwent more
      invasive procedures to obtain a final diagnosis, and a complete follow-up was
      possible in 206 patients (87 EBUS-TBB and 119 TBB). RESULTS: Lung cancer was
      diagnosed in 61 patients in the EBUS-TBB group and in 83 patients in the TBB
      group. Pulmonary diseases other than cancer were diagnosed in 26 patients and 36
      patients, respectively. For patients with lung cancer, sensitivity was 0.79 in
      the EBUS group and 0.55 in the TBB group (p = 0.004), and accuracy was 0.85 and
      0.69, respectively (p = 0.007). The analysis of a subset of patients with lesions
      > 3 cm showed no significant difference in diagnostic ability between the two
      procedures. In lesions < 3 cm, we found a considerable decline in TBB sensitivity
      and accuracy (0.31 and 0.50) while EBUS-TBB maintained their diagnostic yield
      (0.75 and 0.83) [p = 0.0002 and p = 0.001, respectively]. A similar difference
      was observed when we compared the sensitivity of the two procedures in lesions <
      2 cm (0.23 vs 0.71, p < 0.001). CONCLUSIONS: EBUS-TBB can be an important option
      in the early diagnosis of peripheral lung cancer, especially in small-sized
      lesions and in patients who are not eligible for surgery.

PMID- 16304313
TI  - Asymptomatic nonsustained ventricular tachycardia during routine stress
      echocardiography.

PMID- 16304314
TI  - The prevalence of pulmonary embolism and pulmonary hypertension in patients with
      type II diabetes mellitus.
AB  - BACKGROUND: Patients with diabetes mellitus (DM) have a hypercoagulable state
      that may increase their risk for thromboembolism. However, the data about this
      association are contradictory in the literature. The goal of this study was to
      evaluate the occurrence of pulmonary embolism (PE) and pulmonary hypertension
      (PHT) in patients with DM after adjusting for coronary artery disease (CAD),
      congestive heart failure (CHF), hypertension, and smoking using a large database.
      METHOD: We used patient treatment file documents to inpatient hospital admissions
      containing discharge diagnoses (International Classification of Diseases, Ninth
      Revision, Clinical Modification [ICD-9-CM] codes) from Veterans Health
      Administration Hospitals. The patients were classified into two groups: a DM
      group with an ICD-9-CM code for DM (293,124), and a control group with an ICD-9
      CM code for hypertension but no DM (552,623). The ICD-9-CM code for PE (415.19)
      and the ICD-9-CM code for PHT (416.0) were used to study prevalence of these
      diseases in DM patients vs control patients. We performed univariate and
      multivariate analyses adjusting for CAD, CHF, and smoking. Continuous variables
      were analyzed by unpaired t test. Binary variables were analyzed by chi(2) and
      Fisher exact tests. RESULTS: PE was present in 2,011 patients with DM (0.7%) vs
      2,759 patients (0.5%) in the control group. PHT was present in 3,356 patients
      with DM (1.1%) vs 3,357 patients (0.6%) in the control group. Using multivariate
      analysis, DM remained independently associated with PE (odds ratio [OR], 1.27;
      95% confidence interval [CI], 1.19 to 1.35; p < 0.001) and with PHT (OR, 1.53;
      95% CI, 1.45 to 1.60; p < 0.001). CONCLUSION: Patients with DM have significantly
      higher prevalence of PE and PHT independent of CAD, hypertension, CHF, or
      smoking. The pathogenesis of this association is not known at this time.

PMID- 16304315
TI  - Acute myocardial infarction complicated by pulmonary embolism after thrombolytic
      therapy: problems in clinical management.

PMID- 16304316
TI  - Estimation of PaCO2 during exercise in children and postoperative pediatric
      patients with congenital heart disease.
AB  - We evaluated how Paco(2) and respiratory variables relate during and after
      exercise and derived a new noninvasive estimation of Paco(2) in children and
      postoperative patients with congenital heart disease. We randomly selected 8
      subjects from each of three categorized groups from our previous studies: 15
      control subjects (8 to 21 years old), 16 Fontan procedure patients (9 to 22 years
      old), and 13 patients after right ventricular outflow tract reconstruction
      (RVOTR) [7 to 21 years old], and used their respiratory variables during exercise
      testing to estimate Paco(2) (study 1). In a stepwise multiple regression
      analysis, end-tidal carbon dioxide tension (Petco(2)), age, ventilatory
      equivalent for carbon dioxide (minute ventilation [Ve]/carbon dioxide production
      [Vco(2)]), and gas exchange ratio (R) were major determinants of Paco(2) in
      control subjects: Paco(2) = 12.0 + 0.54 Petco(2) + 0.15 Ve/Vco(2) - 3.6 R + 0.22
      age (r = 0.86). In addition to Petco(2) and Ve/Vco(2), arterial oxygen saturation
      and tidal volume were additional major determinants for Fontan procedure and
      RVOTR patients, respectively. We derived equations to predict the Paco(2) (r =
      0.92 for Fontan procedure and r = 0.74 for RVOTR). These equations were applied
      to the remaining study subjects to estimate Paco(2) (study 2). Estimated values
      correlated with the measured Paco(2) (r = 0.71 to 0.86), and the mean differences
      for the control subjects, Fontan procedure, and RVOTR patients were - 0.1, - 0.1,
      and - 1.0, with limits of agreement of +/- 3.3, +/- 4.4, and +/- 3.1,
      respectively. Although estimated Paco(2) based on the Jones equation correlated
      with the measured Paco(2) in all groups, their slopes were significantly flatter
      than ours. Paco(2) throughout exercise testing may be estimated in control
      children and postoperative pediatric patients. The Jones equation should be
      applied with great care in pediatric subjects.

PMID- 16304317
TI  - The physical and biological doses of methacholine are different for Mefar MB3 and
      Jaeger APS sidestream nebulizers.
AB  - BACKGROUND: Within a study on respiratory symptoms in rural areas, we used the
      European Community Respiratory Health Survey methacholine challenge protocol. For
      quicker and more reliable handling, we had to change the nebulizer in the
      bronchial challenge system from Mefar model MB3 (Bovezzo, Italy) to Jaeger APS
      Sidestream (similar to Mefar; Wurzburg, Germany). Therefore, we compared the
      physical properties of the two systems, adapted the challenge protocol, and
      compared the results of both systems in subjects with and without airway
      hyperresponsiveness to methacholine. METHOD: The physical properties of both
      systems were characterized by the residual method indicating a similar particle
      size distribution and an average output of 6 muL/s for Mefar MB3 and 1.25 muL/s
      for APS Sidestream. In the comparison study, 34 subjects were included. Airway
      responsiveness was quantified by provocative dose of methacholine causing a 20%
      fall in FEV(1). RESULTS: A significant difference was found between the two
      challenge systems (p =0.004, McNemar test). Nine subjects reached a 20% drop in
      FEV(1) with the APS Sidestream only. The FEV(1) dropped by > 20% using either
      system in eight subjects. In 17 subjects, none of the two systems caused a 20%
      decrease in FEV(1). CONCLUSION: Even if the physical dose is determined with
      elaborate methods, the biological dose may vary between two nebulizer systems,
      causing incomparable outcomes for subjects tested with different systems.

PMID- 16304318
TI  - Occupational asthma and occupational rhinitis in hairdressers.
AB  - BACKGROUND: Hairdressers are at risk for occupational respiratory diseases, but
      the risk factors, causal agents, and underlying mechanisms are not completely
      defined. AIM: To describe the features of a large group of hairdressers
      consecutively referred to our center for suspected occupational asthma (OA) over
      an 8-year period, the type of occupational respiratory diseases, the etiologic
      agents, and the diagnostic tests. RESULTS: Forty-seven hairdressers (mean age, 25
      years; range, 17 to 52 years) were studied. On the basis of the response to the
      specific inhalation challenge (SIC), 24 patients received a diagnosis of OA
      (51.1%), which was due to persulfate salts in 21 patients (87.5%), permanent hair
      dyes in 2 patients (8.3%), and latex in 1 patient (4.2%). Thirteen of these 24
      patients (54.2%) also received a diagnosis of occupational rhinitis, which was
      due to persulfate salts in 11 patients (84.6%) and to paraphenylenediamine in two
      patients (15.4%). Patients with persulfate asthma had a long period of exposure
      to bleaching agents, a long latent period between the start of exposure and the
      onset of symptoms, and a prevalent eosinophilic airway inflammation in induced
      sputum. The skin-prick test with ammonium persulfate performed in a subset of
      patients gave negative results CONCLUSIONS: In the present study, we confirmed
      that persulfate salts are the major agents involved in OA and occupational
      rhinitis in hairdressers. The positive response to the SIC in only a part of the
      population of symptomatic exposed workers, the period between the starting of
      exposure and the onset of symptoms, the type of response to the SIC, and the high
      frequency of association of asthma with other diseases such as dermatitis and
      rhinitis suggest an immunologic mechanism that remains to be elucidated.

PMID- 16304319
TI  - Palliative and end-of-life care for patients with cardiopulmonary diseases:
      American College of Chest Physicians position statement.
AB  - Acute and chronic pulmonary and cardiac diseases often have a high mortality
      rate, and can be a source of significant suffering. Palliative care, as described
      by the Institute of Medicine, "seeks to prevent, relieve, reduce or soothe the
      symptoms of disease or disorder without effecting a cure... Palliative care in
      this broad sense is not restricted to those who are dying or those enrolled in
      hospice programs." The American College of Chest Physicians strongly supports the
      position that such palliative and end-of-life care of the patient with an acute
      devastating or chronically progressive pulmonary or cardiac disease and his/her
      family should be an integral part of cardiopulmonary medicine. This care is best
      provided through an interdisciplinary effort by competent and experienced
      professionals under the leadership of a knowledgeable and compassionate
      physician. To that end, it is hoped that this statement will serve as a framework
      within which physicians may develop their own approach to the management of
      patients requiring palliative care.

PMID- 16304320
TI  - Macrolides: a treatment alternative for bronchiolitis obliterans organizing
      pneumonia?
AB  - Some macrolides have been found to exert anti-inflammatory effects. Lung diseases
      such as asthma, panbronchiolitis, cystic fibrosis, and bronchiectasis are thought
      to respond to the immunomodulatory properties of macrolides. We report three
      cases of idiopathic bronchiolitis obliterans organizing pneumonia, now called
      cryptogenic organizing pneumonia, and three cases of radiation-related
      bronchiolitis obliterans organizing pneumonia that responded to macrolide
      therapy. An explanation of why macrolides may have anti-inflammatory effects in
      patients with these syndromes is discussed. These cases help to reinforce
      accumulating data that macrolides are beneficial as anti-inflammatory agents and
      organizing pneumonia may be another pulmonary disease that can benefit from such
      therapy.

PMID- 16304321
TI  - Neurohumoral activation as a link to systemic manifestations of chronic lung
      disease.
AB  - COPD is a major cause of death and disability worldwide. Treatment of COPD
      improves lung function but is unlikely to slow the steady downhill course of the
      disease or reduce mortality. In COPD, numerous abnormalities can be found outside
      the lung. These include systemic inflammation, cachexia, and skeletal muscle
      dysfunction. Thus, COPD has been called a systemic disease. Convincing data
      demonstrate that COPD causes neurohumoral activation. By precedents derived from
      chronic heart failure and other diseases characterized by neurohumoral
      activation, we propose that the negative consequences of neurohumoral activation,
      namely inflammation, cachexia, effects on ventilation, and skeletal muscle
      dysfunction, give rise to a self-perpetuating cycle that contributes to the
      pathogenesis of COPD, and which may involve respiratory muscle dysfunction as
      well as systemic inflammation. This concept may further help explain the
      increased cardiovascular morbidity and mortality in COPD patients. Currently,
      little is known about the effect of treatments directed at neurohumoral
      activation and COPD. As this aspect of COPD becomes better understood, new
      insights may direct novel therapeutic approaches.

PMID- 16304322
TI  - Dyspnea and hemoptysis develop in a young man with prostatitis.

PMID- 16304323
TI  - Hypoxemic respiratory failure in a 57-year-old woman with acute monocytic
      leukemia.

PMID- 16304324
TI  - A 50-year-old man with clubbing has seizures after a dental procedure.

PMID- 16304325
TI  - Right atrial pressure: determinant or result of change in venous return?
AB  - According to the concept of Guyton, cardiac output is largely controlled by
      venous return, which is determined by the difference between mean systemic venous
      pressure and right atrial pressure. In the analysis of the venous return curve,
      other authors have suggested that right atrial pressure is the dependent variable
      and venous return is the independent variable (right atrial pressure decreased
      because cardiac output increased). The present report analyzes this historical
      debate, which has already lasted > 50 years.

PMID- 16304326
TI  - In-hospital initiation of statin therapy in acute coronary syndromes: maximizing
      the early and long-term benefits.
AB  - Patients with acute coronary syndrome (ACS) are at high risk for recurrent
      coronary events, sudden death, and all-cause mortality. Conventional
      revascularization therapies reduce the risk of further ischemia but do not affect
      the underlying atherosclerotic disease. Statins have a proven record in the
      secondary prevention of coronary heart disease. Furthermore, statins have been
      shown to exert varying degrees of pleiotropic effects, which may stabilize
      vulnerable atherosclerotic plaques. A compelling body of evidence from randomized
      controlled trials demonstrates that high-dose, potent statin therapy initiated
      immediately after an acute coronary event can significantly reduce early as well
      as longer-term morbidity and mortality. Furthermore, high-dose, potent statin
      therapy displays a reasonable safety profile. National guidelines now recommend
      that in patients with ACS, statin therapy should be initiated in hospital prior
      to discharge, irrespective of baseline low-density lipoprotein cholesterol
      levels, to improve clinical outcomes. Every effort should be made to ensure all
      eligible patients with ACS are initiated and maintained on statin therapy.

PMID- 16304327
TI  - Transesophageal echocardiographic evaluation of diastolic function.
AB  - Diastolic dysfunction is increasingly recognized as a cause of hemodynamic
      instability in the perioperative setting. Difficulty weaning from cardiopulmonary
      bypass and an increased need for inotropic support can occur in the absence of
      systolic impairment. Diastolic dysfunction can also impede hemodynamic
      stabilization and weaning progress in the mechanically ventilated critically ill
      patient. The use of transesophageal echocardiography in the ICU can assist in
      diagnosing the presence and progression of diastolic impairment, which may help
      to target therapeutic interventions that lead to positive outcomes. This review
      summarizes the conventional and new echocardiographic modalities for evaluating
      diastolic function in the perioperative setting.

PMID- 16304328
TI  - Postoperative cognitive dysfunction after cardiac surgery.
AB  - Prolonged postoperative cognitive dysfunction (POCD) is reported to occur
      frequently after cardiac surgery. However, it is rarely assessed in routine
      clinical practice and receives little attention. Although the cerebral
      consequences of cardiopulmonary bypass have been measured clinically, insights
      into the resulting molecular and pathologic events within the brain have only
      begun to be investigated. POCD is likely to impair quality of life and
      constitutes a large burden on society when elderly patients prematurely lose
      their independence. Numerous studies have reported that neurocognitive deficit is
      associated with heightened mortality, increased length of hospital stay, and
      discharge to a nursing home. This is linked with a tremendous demand for health
      care resources. Because of the magnitude of the clinical problem, serious
      consideration must be directed toward understanding its etiology and the
      development of neuroprotective strategies. Clearly identifying the mechanisms of
      POCD is challenging. The purpose of this review is to discuss recent developments
      in our understanding of the pathophysiologic mechanisms, prevention, and
      treatments that have been designed to ameliorate brain dysfunction after cardiac
      surgery.

PMID- 16304329
TI  - Hemoptysis with multiple tracheal nodules.

PMID- 16304330
TI  - Clinical characteristics and outcome of severe melioidosis requiring intensive
      care.
AB  - STUDY OBJECTIVE: To describe the clinical characteristics and outcome of patients
      with severe melioidosis requiring intensive care. DESIGN: Retrospective chart
      review. SETTING: Two ICUs from a tertiary-care teaching hospital. PATIENTS:
      Twenty-seven adult ICU patients with microbiologically documented melioidosis.
      INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The median age was 59 years with a
      male preponderance (26:1). Twenty patients (74%) had medical comorbidities, with
      diabetes mellitus being the most common (59.3%). Almost all patients (96.3%) were
      bacteremic. Twenty patients (74.1%) presented with pneumonia. Twenty patients
      (74.1%) were in septic shock, and 16 patients (59.3%) had ARDS. Twelve patients
      (44.4%) required hemodialysis. The patients had a median of three organ
      dysfunctions, and the median APACHE (acute physiology and chronic health
      evaluation) II score was 27. The overall mortality was 48.1%. Mortality among
      patients with septic shock was 60%. The median ICU length of stay for survivors
      and nonsurvivors was 11 days and 2 days, respectively. Multivariate analysis
      revealed that the number of organ dysfunctions is an independent predictor of
      mortality (odds ratio, 8.2; 95% confidence interval, 1.3 to 51.4). CONCLUSIONS:
      The outcome of severe melioidosis requiring intensive care is poor, with death
      being predicted by the number of organ dysfunctions.

PMID- 16304331
TI  - Alkaptonuria diagnosed by flexible bronchoscopy.
AB  - A 68-year-old white man was evaluated for failure to wean from mechanical
      ventilation after cardiac surgery. Bronchoscopy performed prior to percutaneous
      dilatational tracheotomy revealed circumferential strikingly dark-colored
      airways, most prominent in the trachea and mainstem bronchi, extending distally
      into all airways with overlying desiccated black secretions. Histologic
      examination of bronchial mucosal biopsy samples and the desiccated secretions
      showed acute bronchitis and necrotic debris, respectively. This finding and the
      patient's history led to testing for plasma homogentisic acid, which was found to
      be elevated at 12.6 mug/mL, establishing the first diagnosis of alkaptonuria made
      using flexible bronchoscopy.

PMID- 16304332
TI  - Strongyloides hyperinfection presenting as acute respiratory failure and gram
      negative sepsis.
AB  - STUDY OBJECTIVES: Disseminated strongyloides is a rarely reported phenomenon and
      occurs in immunosuppressed patients with chronic Strongyloides stercoralis
      infection. Typically, patients present with pulmonary symptoms but subsequently
      acquire Gram-negative sepsis. Several cases have been noted in Minnesota, and
      their presentation, diagnostic evaluation, and clinical outcomes were reviewed.
      DESIGN: A retrospective chart review was conducted of complicated strongyloides
      infections from 1993 to 2002 in Minneapolis and St. Paul, MN. Cases were
      identified by reviewing hospital microbiology databases. SETTING: Metropolitan
      hospitals with large immigrant populations. RESULTS: Nine patients, all of
      Southeast Asian heritage, were identified. Eight patients immigrated to the
      United States > or = 3 years prior to acute presentation. All patients were
      receiving antecedent corticosteroids; in five patients, therapy was for presumed
      asthma. Absolute eosinophil counts > 500/microL occurred in only two patients
      prior to steroid initiation. Eight patients presented with respiratory distress,
      and Gram-negative sepsis developed in four patients. Four patients had evidence
      of right-heart strain on ECG or echocardiography at the time of presentation.
      Three patients died; all had eosinophil counts of < 400/microL. CONCLUSIONS:
      Serious complications, including death, may occur in patients with chronic
      strongyloides infection treated with corticosteroids. Strongyloides
      hyperinfection usually presents as acute respiratory failure and may initially
      mimic an asthma exacerbation or pulmonary embolism. Southeast Asian patients
      presenting with new-onset "asthma," acute respiratory distress, and/or Gram
      negative sepsis should undergo evaluation to exclude strongyloides infection.

PMID- 16304333
TI  - High cessation rates of cigarette smoking in subjects with and without COPD.
AB  - BACKGROUND/OBJECTIVE: In general, smoking cessation programs have low success
      rates. We evaluated the effectiveness of a 1-year smoking cessation program. This
      program was part of a research project investigating the effects of smoking
      cessation. PARTICIPANTS: In this longitudinal study on the effects of 1 year of
      smoking cessation, 38 smokers with COPD or chronic bronchitis (mean age, 55
      years; 20 men) and 25 healthy subjects (mean age, 50 years; 11 men) who smoked on
      average 22 cigarettes per day were recruited. METHODS AND RESULTS: An experienced
      nurse and a researcher conducted an intensive nonpharmacologic smoking cessation
      program based on 15 group meetings of 8 to 10 participants. A uniquely high
      number of 16 COPD or chronic bronchitis patients (42%) and 17 healthy subjects
      (68%) did not smoke 1 year after stopping smoking. CONCLUSION: We suggest that
      frequent and intensive motivational support in a research setting accounts for
      the high cessation rates.

PMID- 16304334
TI  - Balloon-facilitated percutaneous dilational tracheostomy tube placement:
      preliminary report of a novel technique.
AB  - OBJECTIVE: To describe a novel technique for percutaneous tracheotomy (PT) that
      could be an alternative to current dilational techniques. DESIGN: An
      observational animal study of PT was performed using the Seldinger guide wire
      technique with a tracheostomy tube preloaded onto a dilational balloon catheter.
      A small skin incision was done with an 11-blade scalpel, but no blunt
      subcutaneous tissue dissection was performed. SETTING: Animal laboratory in a
      university hospital. SUBJECTS: Seven adult pigs (approximate weight, 16 to 21
      kg). MEASUREMENTS AND RESULTS: Successful tracheostomy was accomplished in all
      seven pigs without apparent complication. Vital signs and oximetry results
      remained unchanged throughout the procedure. The mean duration of the procedure
      was 5.5 min from tracheal puncture to ventilation. CONCLUSION: This novel
      procedure is a simple and effective means of PT tube placement without
      subcutaneous tissue dissection and could potentially have decreased complications
      when compared to the standard methods of PT currently employed in humans. Human
      studies are pending.

PMID- 16304335
TI  - Effects of gas leak on triggering function, humidification, and inspiratory
      oxygen fraction during noninvasive positive airway pressure ventilation.
AB  - OBJECTIVES: During noninvasive positive pressure ventilation (NPPV), the gas leak
      that commonly occurs around the mask can render NPPV ineffective. We evaluated
      the effects of gas leak on inspiratory trigger function during NPPV with bilevel
      pressure and ICU ventilators. In addition, we evaluated the effects of gas leak
      on fraction of inspired oxygen (Fio(2)) and humidification. METHODS: Air leak was
      created at the airway opening of a model lung by establishing several different
      size holes in the circuit. During simulated spontaneous breathing, we evaluated
      inspiratory trigger performance of two bilevel pressure ventilators (BiPAP Vision
      and BiPAP S/T-D; Respironics; Murrysville, PA) and two ICU ventilators (Puritan
      Bennett 7200ae and Puritan-Bennett 840; Tyco Healthcare; Mansfield, MA).
      Inspiratory delay time and inspiratory trigger pressure were analyzed. Fio(2) at
      the airway opening and inside the model lung were evaluated during BiPAP S/T-D
      ventilation at supplemental oxygen flows of 3, 6, 9, 12 and 15 L/min. Measured
      oxygen concentration was compared to mathematically predicted levels. Finally,
      using two heated humidifiers, we evaluated the effect of gas leak on
      humidification. RESULTS: The bilevel pressure ventilators triggered properly at
      all levels of gas leak, and inspiratory triggering was more effective than with
      the ICU ventilators. Delivered Fio(2) with the BiPAP S/T-D ventilator was
      affected by gas leak and could be predicted mathematically unless the gas leak
      was large. With large gas leaks, although relative humidity was maintained,
      absolute humidity decreased. CONCLUSION: Gas leak affected triggering of ICU
      ventilators, Fio(2) of the BiPAP S/T-D ventilator, and humidity with both types
      of humidifiers.

PMID- 16304336
TI  - An in vitro evaluation of the effectiveness of endotracheal suction catheters.
AB  - INTRODUCTION: Tracheal suction catheters (TSCs) are used to clear mucus from an
      endotracheal tube (ETT). The clearance rate is critical because airway mucus
      stasis leads to obstruction, but prolonged catheter suctioning can lead to
      hypoxemia. The rate of mucus clearance from an ETT is thought to be influenced by
      the properties of the mucus, the pressure used to suction the mucus, and the
      diameter of the catheter. In this study, different adult TSCs were evaluated for
      their ability to suction mucus simulants that had properties similar to airway
      mucus. METHODS: Six different 14F TSC designs were evaluated. All catheters had
      the same end hole size, but the two side holes were sized at 3 mm, 4 mm, or 5 mm.
      A coagulant (Polyox Water Soluble Resin Coagulant NF; Dow Chemical Company; Cary,
      NC) was mixed with water at concentrations of 0.5%, 1.5%, and 3.0% to simulate
      mucus or sputum. Suction effectiveness was evaluated by the mass percentage of
      the coagulant suctioned over 10 s at 100 mm Hg from an 8.0 ETT. MEASUREMENTS AND
      RESULTS: The 1.5% and 3.0% simulants had properties comparable to human airway
      mucus and sputum. Suction effectiveness was less with the 3.0% coagulant simulant
      compared with the 1.5% and 0.5% simulants. Suction effectiveness was greater (p <
      0.01) with TSCs that had nonparallel holes and a side hole diameter of 5 mm when
      tested with the 1.5% and 3.0% simulants. However, no best catheter could be
      identified among TSCs when tested with the more liquid-like 0.5% simulant.
      CONCLUSIONS: Greater TSC side hole diameter and nonparallel positioning was
      important for suctioning mucus simulants that are similar to mucus or sputum. The
      distance between side holes, end hole size, suction force, and duration of
      suctioning were not tested but could also have an effect on TSC performance.

PMID- 16304337
TI  - L-arginine attenuates acute pulmonary embolism-induced increases in lung matrix
      metalloproteinase-2 and matrix metalloproteinase-9.
AB  - STUDY OBJECTIVES: To evaluate the effects of L-arginine on acute pulmonary
      embolism (APE)-induced pulmonary hypertension and increases in lung matrix
      metalloproteinase (MMP)-2 and MMP-9 activities. DESIGN: Prospective trial.
      SETTING: University laboratory. INTERVENTIONS: Using an isolated lung perfusion
      rat model of APE, we examined whether L-arginine (0, 0.5, 3, and 10 mmol/L; five
      to seven rats per group) attenuates the pulmonary hypertension induced by the
      injection of 6.6 mg/kg of 300 microm microspheres into the pulmonary artery. In a
      second series of experiments (6 to 11 rats per group), we investigated whether
      nonselective inhibition of nitric oxide (NO) synthases with N(G)-nitro-L-arginine
      methyl ester (L-NAME; 4 mmol/L) decreases the effects produced by L-arginine.
      Lung MMP-2 and MMP-9 activities were determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis gelatin zymography. RESULTS: L-arginine at
      0.5, 3, and 10 mmol/L attenuated APE-induced pulmonary hypertension by 25 to 42%
      (all p < 0.05). The protective effect of L-arginine was completely reversed by
      inhibition of NO synthesis with L-NAME. APE was associated with increased lung
      MMP-2 and MMP-9 activities (both p < 0.05). While L-arginine at 0.5 mmol/L
      produced no effect on MMPs, L-arginine 3 at mmol/L and 10 mmol/L attenuated the
      increases in MMP-2 and MMP-9 activities after APE (both p < 0.05). CONCLUSIONS: L
      arginine attenuates APE-induced pulmonary hypertension through mechanisms
      involving increased NO synthesis and maybe attenuation of lung MMP-2 and MMP-9
      activities.

PMID- 16304338
TI  - Suitability of caspofungin for aerosol delivery: physicochemical profiling and
      nebulizer choice.
AB  - BACKGROUND: Aerosolized antifungal therapy is a promising route of drug delivery
      for pulmonary aspergillosis due to attainment of high localized concentrations.
      Caspofungin, a new antifungal agent with proven efficacy against invasive
      aspergillosis, has ideal potential for aerosolization. STUDY OBJECTIVE: To
      examine in vitro the suitability of caspofungin for aerosol administration by
      characterizing factors that influence efficacy and airway tolerance of aerosol
      delivery: physicochemical properties, aerodynamics of drug particles, and
      efficiency of nebulizing systems. DESIGN: Physicochemical characteristics of
      caspofungin solutions (10 mg/mL and 30 mg/mL) were analyzed: osmolality, pH,
      viscosity, and surface tension. A time-of-flight aerosol spectrometer API
      Aerosizer was used to determine aerosol particle size and distribution. Drug
      output was quantified by high-performance liquid chromatography assay. Nebulizer
      efficiency was measured by drug output and respirable fraction (percentage of
      aerosolized particles with a 1 to 5 mum aerodynamic diameter) and compared among
      three jet nebulizer/compressor systems: device 1, Micromist (Hudson RCI;
      Temecula, CA)/Pulmo-Aide (model 5650D; DeVilbiss; Somerset, PA); device 2,
      Sidestream MS 2400/Envoy model IRC 1192 (Invacare; Elyria, OH); and device 3,
      Pari LC Star/Proneb Ultra (Pari Respiratory Equipment; Midlothian, VA).
      MEASUREMENTS AND RESULTS: Caspofungin requires 0.9% NaCl rather than sterile
      water as the diluent and addition of 0.3N NaOH buffer to adjust acidity of
      solutions (pH 6.17 to 6.26) in order to achieve optimal physicochemical
      properties for airway tolerability (osmolality, 150 to 550 milliosmol per
      kilogram; chloride ion, 31 to 300 mmol/L; and pH 7.4). The drug output rate
      increased with higher concentrations of drug solution: device 1, 4.0 mg/min vs
      12.5 mg/min; device 2, 5.4 mg/min vs 14.7 mg/min; and device 3, 2.3 mg/min vs 12
      mg/min, respectively. The percentage of particles within the respirable range
      varies depending on device and concentration of drug solutions (10 mg/mL vs 30
      mg/mL): device 1, 85% vs 38%; device 2, 44% vs 57%; and device 3, 83% vs 93%,
      respectively. CONCLUSION: Caspofungin solution with adjustments appears to have
      physicochemical and aerodynamic characteristics suitable for aerosolization when
      used with either the Pari LC Star/Proneb Ultra or Micromist/Pulmo-Aide devices.
      Further in vivo testing is warranted.

PMID- 16304339
TI  - Prostaglandin E2 receptor selective agonists E-prostanoid 2 and E-prostanoid 4
      may have therapeutic effects on ovalbumin-induced bronchoconstriction.
AB  - BACKGROUND: The pharmacologic actions of prostaglandin E(2) (PGE(2)) are mediated
      through specific E-prostanoid (EP)-1, EP-2, EP-3, and EP-4 receptors. In this
      study, we determined which PGE(2) receptor subtype(s) contribute to the
      prevention of allergen-induced bronchoconstriction. METHODS: We assessed the
      effects of these receptor agonists in ovalbumin (OA)-sensitized guinea pigs. The
      prostaglandin E receptor-subtype agonists tested were ONO-DI-004 (EP-1), ONO-AE1
      259 (EP-2), ONO-AE-248 (EP-3), ONO-AE1-329 (EP-4), and sulprostone (EP-1 and EP
      3) [Ono Pharmaceutical Company; Osaka, Japan]. We treated the animals with either
      PGE(2) or these agonists 15 min before OA challenge and measured respiratory
      resistance at 15 min, 1 h, and 3 h. RESULTS: Allergen-induced bronchoconstriction
      was significantly (p < 0.01) suppressed at doses > 85 nmol/kg of PGE(2). The
      respiratory resistance elevations 15 min after OA challenge were significantly (p
      < 0.01) suppressed by preadministration of EP-2 and EP-4 agonists, but airway
      responsiveness to inhaled methacholine did not improve. EP-1, EP-3, or EP-1/EP-3
      agonists had no effect on any parameter. CONCLUSIONS: These results suggest that
      inhibition of OA-induced bronchoconstriction by PGE(2) acts through EP-2 and EP-4
      receptors.

PMID- 16304340
TI  - Expression of CXC chemokine receptors 1 and 2 in human bronchial epithelial
      cells.
AB  - INTRODUCTION: CXC chemokine receptor 1 (CXCR1) and CXC chemokine receptor 2
      (CXCR2) have been shown to play an important role in transepithelial migration of
      neutrophil granulocytes during inflammation in various tissues. This study
      investigated the regulation of gene expression and surface expression of CXCR1
      and CXCR2 in a human bronchial epithelial cell line (BEAS-2B), as well as in
      primary bronchial epithelial cells (PBECs) from 10 COPD patients and 10 control
      subjects. METHODS AND RESULTS: The transcription expression of CXCR1 and CXCR2
      was quantitatively assessed by means of real-time polymerase chain reaction (PCR)
      under various inflammatory conditions. Flow cytometry was used to measure CXCR1
      and CXCR2 surface expression. There was a low baseline expression of CXCR1 and
      CXCR2 in real-time PCR in PBECs from COPD patients and control subjects as well
      as in BEAS-2B cells, and no significant regulation occurred under various
      inflammatory conditions in PBECs and BEAS-2B cells. Furthermore, unstimulated
      surface expression of CXCR1 and CXCR2 on BEAS-2B cells was very low, and no
      significant regulation was detectable under time-dependent inflammatory
      stimulation up to 24 h. CONCLUSION: Various inflammatory responses that are of
      potential relevance in COPD pathophysiology do not affect transcription
      regulation and surface expression of the interleukin-8 receptors CXCR1 and CXCR2
      on human bronchial epithelial cells.

PMID- 16304341
TI  - Combination therapy with intrapleural doxycycline and talc in reduced doses is
      effective in producing pleurodesis in rabbits.
AB  - BACKGROUND: It has been suggested that talc and doxycycline might be acting
      through different pathways in creating pleurodesis. We hypothesized that
      combining doxycycline and talc in half the usual doses would be synergistic in
      inducing pleurodesis. METHODS: Thirty-two rabbits were equally allocated into
      four groups: group 1, half-dose combination (5 mg/kg of doxycycline and 200 mg/kg
      of talc slurry); group 2, quarter-dose combination (2.5 mg/kg of doxycycline and
      100 mg/kg of talc slurry); group 3, half-dose doxycycline (5 mg/kg of
      doxycycline); and group 4, half-dose talc (100 mg/kg of talc slurry). The
      pleurodesis scores from historical groups that received a full dose of talc (400
      mg/kg) or doxycycline (10 mg/kg) were also compared to those obtained in the
      current study. Pleural fluid lactate dehydrogenase and protein levels were
      measured 24 h after the injection. Pleurodesis was graded from 1 (none) to 8 (>
      50% symphysis) by two observers blinded to treatment groups. All rabbits
      underwent an ultrasonic examination on each side of their chest for the
      evaluation of pleurodesis. RESULTS: The mean pleurodesis score in the half-dose
      combination group was significantly higher than that in the half-dose talc group,
      half-dose doxycycline group, and the historical full-dose talc group (p = 0.009,
      p = 0.01, and p < 0.05, respectively). The quarter-dose combination group also
      had a significantly higher mean pleurodesis score compared to the half-dose talc
      group (p = 0.013). The difference between the historical full-dose doxycycline
      and the half-dose combination or quarter-dose combination groups was not
      significant (p > 0.05). A significantly positive correlation existed between the
      pleurodesis score and the ultrasound scores (r = 0.876, p = 0.000000005).
      CONCLUSIONS: This study demonstrates that the combination of half doses of talc
      and doxycycline is more effective than the half dose of either drug alone or the
      full dose of talc in producing pleurodesis in rabbits. In addition, ultrasound is
      an accurate imaging modality for the evaluation of pleurodesis, in that the
      absence of pleural gliding on ultrasound correlates well with the presence of a
      pleurodesis in rabbits.

PMID- 16304342
TI  - Comparative effects of salmeterol, albuterol, and ipratropium on normal and
      impaired mucociliary function in sheep.
AB  - STUDY OBJECTIVE: We measured tracheal mucus velocity (TMV), a marker of
      mucociliary clearance (MCC), in sheep before and for 12 h after treatment with
      salmeterol, albuterol, ipratropium, or vehicle to determine the effects on normal
      MCC. We also determined if these agents could reverse the depression in TMV
      caused by inhaled human neutrophil elastase (HNE), a model of abnormal MCC.
      METHODS: Study 1: TMV was measured initially and then for 6 h after metered-dose
      inhaler treatment with salmeterol (42 microg), albuterol (180 microg),
      ipratropium bromide (36 microg), or vehicle. After 6 h, the sheep in the
      albuterol and ipratropium treatment arms were administered a second dose of drug,
      whereas the salmeterol and vehicle treatment arms received vehicle. TMV was
      measured for another 6 h. Study 2: Six sheep inhaled HNE aerosol, which
      significantly reduced TMV by 2 h. At this point, the sheep were treated with
      either salmeterol, albuterol, ipratropium, or vehicle, and the effects on TMV
      were measured for another 6 h. This experiment was repeated in four sheep using
      only salmeterol and albuterol, but the posttreatment measurements were extended
      to 12 h. RESULTS: Study 1: Only salmeterol and albuterol increased TMV (p < 0.05)
      during the initial 6-h period. From 6 to 12 h only, the salmeterol-treated sheep
      had TMV that remained at or above the initial TMV for the entire time, although
      both albuterol and ipratropium showed enhancement of TMV compared to vehicle.
      Study 2: Salmeterol and albuterol reversed the HNE-induced depression in TMV to a
      similar degree over the 6-h time course. However, the protection afforded by
      salmeterol was more prolonged than that seen with albuterol if the posttreatment
      interval was extended to 12 h. Ipratropium and vehicle had no effect. CONCLUSION:
      We conclude that salmeterol and albuterol can stimulate normal MCC and reverse
      HNE-induced mucociliary dysfunction and that salmeterol has a longer duration of
      action in these models of normal and abnormal MCC.

PMID- 16304343
TI  - Oral forms of tetracycline and doxycycline are effective in producing
      pleurodesis.
AB  - PURPOSES: We investigated whether oral tetracyclines could produce an efficient
      and safe pleurodesis as does parenteral doxycycline, which is currently
      unavailable in many countries. METHODS: Parenteral doxycycline (10 mg/kg), oral
      tetracycline (35 mg/kg), or doxycycline (10 mg/kg) was injected intrapleurally
      through a right chest tube in rabbits. The oral forms were dissolved in saline
      solution and passed through a sterile membrane filter. When daily aspirated
      pleural fluid was < 5 mL/24 h, the chest tube was removed. Fluid WBC, lactate
      dehydrogenase (LDH), and protein levels were measured 24 h after the injection.
      After the death of the animals on day 14, pleurodesis was graded from 1 (none) to
      8 (> 50% symphysis) by two observers blinded to treatment groups. RESULTS: The
      right pleurodesis score of the combined oral groups (median, 7.0; interquartile
      range [IQR], 4.0; n = 26) did not differ significantly (p = 0.349) from that of
      the parenteral group (median, 7.5; IQR, 6.0; n = 10). Oral tetracycline (capsule
      or tablet, n = 6 in each group) and doxycycline (capsule or tablet, n = 7 in each
      group) were as effective as parenteral doxycycline in producing pleurodesis:
      tetracycline capsule (median, 7.50; IQR, 6.00); tetracycline tablet (median,
      6.50; IQR, 6.00); doxycycline capsule (median, 4.00; IQR, 1.00); doxycycline
      tablet (median, 8.00; IQR, 5.00), and parenteral doxycycline (median, 7.50; IQR,
      6.00) [p = 0.235]. The left pleurodesis scores were 1.00 in all 36 rabbits. Fluid
      total volume, WBC, LDH, and protein levels were comparable between each oral and
      parenteral group, excluding WBCs in the tetracycline tablet group (p = 0.047).
      The complications were nonfatal (right hemothorax: tetracycline capsule [n =
      3]/tetracycline tablet [n = 2], doxycycline tablet [n = 2], parenteral
      doxycycline [n = 2]; left hemothorax: tetracycline capsule [n = 1]; ascites:
      parenteral doxycycline [n = 1]). There was no growth on all filtrate cultures.
      Oral forms cost less than parenteral doxycycline (<1 US dollar vs 4.72 US dollars
      per rabbit). Filtering costs were 1.12 US dollars per rabbit. CONCLUSION: Oral
      tetracycline or doxycycline is as effective and safe as parenteral doxycycline in
      producing pleurodesis in rabbits; thus, they may also be used in humans.

PMID- 16304344
TI  - Analysis of atelectasis, ventilated, and hyperinflated lung during mechanical
      ventilation by dynamic CT.
AB  - STUDY OBJECTIVE: To study the dynamics of lung compartments by dynamic CT (dCT)
      imaging during uninterrupted pressure-controlled ventilation (PCV) and different
      positive end-expiratory pressure (PEEP) settings in healthy and damaged lungs.
      DESIGN: Experimental animal investigation. SETTING: Experimental animal facility
      of a university department. INTERVENTIONS: In seven anesthetized pigs, static
      inspiratory pressure volume curves were obtained to identify the individual lower
      inflection point (LIP) before and after saline solution lung lavage. During PCV,
      PEEP was adjusted 5 millibars (mbar) below the individually determined LIP (LIP -
      5), at the LIP, and 5 mbar above the LIP (LIP + 5). MEASUREMENTS AND RESULTS:
      Measurements were repeated before and after induction of lung damage.
      Hemodynamics, arterial and mixed venous blood gases, and dCT imaging in one
      juxtadiaphragmatic slice (effective temporal resolution of 100 ms) were assessed
      during uninterrupted PCV in series of three successive respiratory cycles. The
      mean fractional area (FA) of the hyperinflated lung (FA-H), mean FA of ventilated
      lung, mean FA of poorly ventilated lung, and mean FA of nonventilated lung (FA
      NV), and the change in FA of the whole lung area (DeltaFA) were compared at
      different PEEP settings. Calculated pulmonary shunt (Qs/Qt) was compared to FA
      NV. LIP + 5 decreased the amount of atelectasis (FA-NV) and increased
      hyperinflation (FA-H) in healthy and injured lungs. Cyclic changes of atelectasis
      (DeltaFA-NV) and hyperinflation (DeltaFA-H) were observed in both healthy and
      injured lungs. In the injured but not in the healthy lungs, the amount of cyclic
      changes of atelectasis and hyperinflation were independent from the adjusted PEEP
      level. FA-NV correlated with the calculated Qs/Qt, with a slight overestimation
      (mean +/- SEM, 2.1 +/- 4.1%). CONCLUSIONS: dCT imaging allows the following: (1)
      the quantification of the extent of atelectasis, ventilated, poorly ventilated,
      and hyperinflated lung parenchyma during ongoing mechanical ventilation; (2) the
      detection and quantification of repeated recruitment and derecruitment, as well
      as hyperinflation; and (3) an estimation of Qs/Qt. dCT adds promising functional
      information for the respiratory treatment of early ARDS.

PMID- 16304345
TI  - Is the arteriovenous carboxyhemoglobin gradient really a useful marker in
      systemic inflammation?

PMID- 16304346
TI  - The puzzling relationship between cigarette smoking, reduced respiratory
      function, and systemic inflammation.

PMID- 16304347
TI  - Probabilistic risk assessment and performance index applications for the ICU.

PMID- 16304348
TI  - Is the method of modified percutaneous tracheostomy without bronchoscopic
      guidance really simple and safe?

PMID- 16304349
TI  - Decisions for critically ill patients.

PMID- 16304350
TI  - Prevention of venous thromboembolism.

PMID- 16304351
TI  - Regulation of AMP-activated protein kinase and acetyl-CoA carboxylase
      phosphorylation by palmitate in skeletal muscle cells.
AB  - The purpose of this study was to investigate the effects of long-chain fatty
      acids (LCFAs) on AMP-activated protein kinase (AMPK) and acetyl-coenzyme A
      carboxylase (ACC) phosphorylation and beta-oxidation in skeletal muscle. L6 rat
      skeletal muscle cells were exposed to various concentrations of palmitate (1-800
      microM). Subsequently, ACC and AMPK phosphorylation and fatty acid oxidation were
      measured. A 2-fold increase in both AMPK and ACC phosphorylation was observed in
      the presence of palmitate concentrations as low as 10 microM, which was also
      accompanied by a significant increase in fatty acid oxidation. The effect of
      palmitate on AMPK and ACC phosphorylation was dose-dependent, reaching maximum
      increases of 3.5- and 4.5-fold, respectively. Interestingly, ACC phosphorylation
      was coupled with AMPK activation at palmitate concentrations ranging from 10 to
      100 microM; however, at concentrations >200 microM, ACC phosphorylation and fatty
      acid oxidation remained high even after AMPK phosphorylation was completely
      prevented by the use of a selective AMPK inhibitor. This indicates that LCFAs
      regulate ACC activity by AMPK-dependent and -independent mechanisms, based on
      their abundance in skeletal muscle cells. Here, we provide novel evidence that
      the AMPK/ACC pathway may operate as a mechanism to sense and respond to the lipid
      energy charge of skeletal muscle cells.

PMID- 16304352
TI  - Venous thrombosis: the role of genes, environment, and behavior.
AB  - Over the last decade we have witnessed an avalanche of newly identified risk
      factors for venous thrombosis. This has advanced our knowledge of its etiology,
      because more determinants have been described and because the underlying concepts
      have received a new and broader understanding. Venous thrombosis is a common
      multicausal disease occurring as the result of interacting genetic, environmental
      and behavioral risk factors. Some of these have been known since medieval times,
      such as the increased risk of thrombosis during immobilization in pregnancy and
      after childbirth (although retained milk of the breast-feeding mother was seen as
      the primary cause for the latter). Pregnancy and puerperium still cause
      thrombosis, as do exogenous hormones in oral contraceptives and hormonal
      replacement therapy. Furthermore, the immobilization in the puerperium of the old
      days translates directly to situations of immobilization in current times, such
      as prolonged travel in airplanes or excessive electronic gaming. While pedigrees
      with abundant thrombosis were observed in the early 1900s, the first cause of
      heritable thrombophilia (antithrombin deficiency) was discovered in 1965, with
      the subsequent identification of deficiencies of protein C and protein S in the
      early 1980s. These were uncommon and strong risk factors, whereas the more
      recently discovered genetic variants are common and weak, and cause disease only
      in the presence of other factors.

PMID- 16304353
TI  - Red cell membrane disorders.
AB  - Disorders of the erythrocyte membrane, including hereditary spherocytosis,
      hereditary elliptocytosis, hereditary pyropoikilocytosis, and hereditary
      stomatocytosis, comprise an important group of inherited hemolytic anemias. These
      syndromes are characterized by marked clinical and laboratory heterogeneity.
      Recent molecular studies have revealed that there is also significant genetic
      heterogeneity in these disorders. This is particularly true for the spherocytosis
      syndromes where each kindred has a private mutation in one of the spherocytosis
      genes. Treatment with splenectomy is curative in most patients. Splenectomy via a
      laparoscopic approach has become the surgical method of choice. Growing
      recognition and understanding of the long-term risks and complications of
      splenectomy, including cardiovascular disease, thrombotic disorders, and
      pulmonary hypertension, and the emergence of penicillin-resistant pneumococci, a
      concern for infection in overwhelming postsplenectomy infection, have led to
      reevaluation of the role of splenectomy. Recent management guidelines acknowledge
      these important considerations when entertaining splenectomy and recommend
      detailed discussion between health care providers, patient, and family.

PMID- 16304354
TI  - Red cell enzymes.
AB  - Mutations leading to red cell enzyme deficiencies can be associated with diverse
      phenotypes that range from hemolytic anemia, methemoglobinemia, polycythemia, and
      neurological and developmental abnormalities. While most of these mutations occur
      sporadically, some such as common glucose-6-phosphate dehydrogenase (G6PD)
      mutants are endemic and rarely cause disease. Common G6PD mutants likely reached
      their prevalence because they provide some protection against severe malarial
      complications. In this review G6PD, pyruvate kinase, 5' nucleotidase, and
      cytochrome b5 reductase deficiencies will be discussed in greater detail.
      Limitations of commonly used screening tests for detection of these disorders
      will also be emphasized, as well as emerging knowledge about non-enzymatic
      function of the glycolytic enzymes.

PMID- 16304355
TI  - Neurovisceral porphyrias: what a hematologist needs to know.
AB  - The acute or inducible hepatic porphyrias comprise four inherited disorders of
      heme biosynthesis. They usually remain asymptomatic for most of the lifespan of
      individuals who inherit the specific enzyme deficiencies but may cause life
      threatening attacks of neurovisceral symptoms. Failure to consider the diagnosis
      frequently delays effective treatment, and inappropriate diagnostic tests and/or
      mistaken interpretation of results may lead to misdiagnosis and inappropriate
      treatment. The four disorders are ALA dehydratase deficiency porphyria, acute
      intermittent porphyria, hereditary coproporphyria, and variegate porphyria. Other
      conditions that clinically and biochemically may mimic acute porphyria include
      lead poisoning and hereditary tyrosinemia type I. The diagnosis of one of these
      acute porphyric syndromes should be considered in many patients with otherwise
      unexplained abdominal pain, severe constipation, systemic arterial hypertension,
      or other characteristic symptoms. Critical to the rapid diagnosis of the three
      most common of these disorders is demonstration of markedly increased urinary
      porphobilinogen (PBG) in a single-void urine specimen. The treatment of choice
      for all but mild attacks of the acute porphyrias is intravenous hemin therapy,
      which should be started as soon as possible. Intravenous glucose alone is
      recommended only for mild attacks (no weakness or hyponatremia) or until hemin is
      available.

PMID- 16304356
TI  - Pathophysiology of beta thalassemia--a guide to molecular therapies.
AB  - The central mechanism underlying the pathophysiology of the beta thalassemias can
      be related to the deleterious effects of imbalanced globin chain synthesis on
      erythroid maturation and survival. An imbalance of the alpha/non-alpha globin
      chains leads to an excess of unmatched alpha globin which precipitates out,
      damaging membrane structures leading to accelerated apoptosis and premature
      destruction of the erythroid precursors in the bone marrow (ineffective
      erythropoiesis). Close observation of the genotype/phenotype relationships
      confirms the pathophysiological mechanism and provides clues to molecular
      therapies, all of which aim to reduce the alpha/non-alpha chain imbalance. They
      include inheritance of the milder forms of beta thalassemia, co-inheritance of
      alpha thalassemia, or genetic factors (quantitative trait loci, QTLs) for
      increasing gamma globin expression. Currently, the most promising molecular
      therapeutic approaches include increasing beta globin gene expression by stem
      cell gene therapy and increasing gamma globin expression using pharmacological
      agents or by transduction of the gamma globin genes.

PMID- 16304357
TI  - Fetal globin induction--can it cure beta thalassemia?
AB  - The beta thalassemias are one of a few medical conditions in which reactivation
      of a gene product that is expressed during fetal life can functionally replace a
      deficiency of essential proteins expressed at a later developmental stage. The
      fetal globin genes are present and normally integrated in hematopoietic stem
      cells, and at least one fetal gene appears accessible for reactivation,
      particularly in beta degrees thalassemia. However, rapid cellular apoptosis from
      alpha globin chain precipitation, and relatively low levels of endogenous
      erythropoietin (EPO) in some beta(+) thalassemia patients contribute to the
      anemia in beta thalassemia syndromes. In clinical trials, three classes of
      therapeutics have demonstrated proof-of-principle of this approach by raising
      total hemoglobin levels by 1-4 g/dL above baseline in thalassemia patients: EPO
      preparations, short chain fatty acid derivatives (SCFADs), and chemotherapeutic
      agents. Although thalassemic erythrocytes survive only for a few days, the
      magnitude of these responses is similar to those induced by rhu-EPO in anemic
      conditions of normal erythrocyte survival. New oral therapeutic candidates, which
      stimulate both fetal globin gene expression and erythropoiesis, and combinations
      of therapeutics with complementary molecular actions now make this gene
      reactivation approach feasible to produce transfusion independence in many
      patients. Development of the candidate therapeutics is hindered largely by costs
      of drug development for an orphan patient population.

PMID- 16304358
TI  - Gene Therapy for beta-thalassemia.
AB  - Gene transfer for beta-thalassemia requires gene transfer into hematopoietic stem
      cells using integrating vectors that direct regulated expression of beta globin
      at therapeutic levels. Among integrating vectors, oncoretroviral vectors carrying
      the human beta-globin gene and portions of the locus control region (LCR) have
      suffered from problems of vector instability, low titers and variable expression.
      In recent studies, human immunodeficiency virus-based lentiviral (LV) vectors
      were shown to stably transmit the human beta-globin gene and a large LCR element,
      resulting in correction of beta-thalassemia intermedia in mice. Several groups
      have since demonstrated correction of the mouse thalassemia intermedia phenotype,
      with variable levels of beta-globin expression. These levels of expression were
      insufficient to fully correct the anemia in thalassemia major mouse model.
      Insertion of a chicken hypersensitive site-4 chicken insulator element (cHS4) in
      self-inactivating (SIN) LV vectors resulted in higher and less variable
      expression of human beta-globin, similar to the observations with cHS4-containing
      retroviral vectors carrying the human gamma-globin gene. The levels of beta
      globin expression achieved from insulated SIN-LV vectors were sufficient to
      phenotypically correct the thalassemia phenotype from 4 patients with human
      thalassemia major in vitro, and this correction persisted long term for up to 4
      months, in xeno-transplanted mice in vivo. In summary, LV vectors have paved the
      way for clinical gene therapy trials for Cooley's anemia and other beta-globin
      disorders. SIN-LV vectors address several safety concerns of randomly integrating
      viral vectors by removing viral transcriptional elements and providing lineage
      restricted expression. Flanking the proviral cassette with chromatin insulator
      elements, which additionally have enhancer-blocking properties, may further
      improve SIN-LV vector safety.

PMID- 16304359
TI  - Cardiopulmonary complications of sickle cell disease: role of nitric oxide and
      hemolytic anemia.
AB  - Medical advances in the management of patients with sickle cell disease,
      thalassemia, and other hemolytic anemias have led to significant increases in
      life expectancy. Improved public health, neonatal screening, parental and patient
      education, advances in red cell transfusion medicine, iron chelation therapy,
      penicillin prophylaxis for children, pneumococcal immunization, and hydroxyurea
      therapy have all likely contributed to this effect on longevity. Importantly, as
      a generation of patients with sickle cell disease and thalassemia ages, new
      chronic complications of these hemoglobinopathies develop. In this context,
      pulmonary hypertension is emerging as one of the leading causes of morbidity and
      mortality in adult sickle cell and thalassemia patients, and likely in patients
      with other hemolytic anemias. A common feature of both sickle cell disease and
      thalassemia is intravascular hemolysis and chronic anemia. Recent data suggest
      that chronic intravascular hemolysis is associated with a state of endothelial
      dysfunction characterized by reduced nitric oxide (NO) bioavailability, pro
      oxidant and pro-inflammatory stress and coagulopathy, leading to vasomotor
      instability and ultimately producing a proliferative vasculopathy, a hallmark of
      which is the development of pulmonary hypertension in adulthood. In conclusion,
      pulmonary hypertension is common in patients with hereditary hemolytic anemias
      and is associated with a high risk of death in patients with sickle cell disease.
      New therapies targeting this vasculopathy and aimed at normalizing the
      vasodilator:vasoconstrictor balance are discussed.

PMID- 16304360
TI  - An evidence-based approach to the treatment of adults with sickle cell disease.
AB  - The application of evidence-based medicine to the management of adults with
      sickle cell disease (SCD) is currently primarily driven by clinical expertise and
      patient preference, as there is a paucity of randomized controlled trial (RCT)
      data to guide decision-making. A summary of SCD management principles in the
      areas of health care maintenance, transfusion therapy, treatment and prevention
      of painful episodes, acute chest syndrome, stroke, renal disease, contraception
      and pregnancy, and priapism is predominantly based on the authors' interpretation
      of available observational studies as well as the opinions of experts in SCD.
      RCTs impacting current practices address use of hydroxyurea to prevent painful
      episodes and acute chest syndrome, intensity of pre-operative transfusion,
      transfusion during pregnancy, and angiotensin-converting enzyme inhibitor therapy
      for proteinuria, but most issues in adult SCD care have not been rigorously
      studied and management may not be appropriately extrapolated from pediatric data.
      While challenging clinical problems need to be addressed by RCTs, there is also
      the need for development of practice guidelines using formal methodological
      strategies. This brief review is not a substitute for the process but provides a
      literature-based approach to making treatment decisions when caring for adults
      with SCD.

PMID- 16304361
TI  - Stem cell therapy for sickle cell disease: transplantation and gene therapy.
AB  - HLA-identical sibling hematopoietic cell transplantation (HCT) for sickle cell
      disease (SCD) has a strong track record of efficacy and there is growing
      appreciation that its benefits exceed its risks in selected individuals. In
      contrast, the clinical utility of replacement gene therapy for sickle cell
      disease remains unproven. Its challenge is to ensure viral transduction into
      hematopoietic stem cells (HSCs) and to generate safe, stable, erythroid-specific
      replacement gene expression at a level that is sufficient to have a clinical
      effect. The clinical necessity for fulfilling all these criteria may make this
      genetic disorder among the most complex to treat successfully by gene therapy.
      But the experience of HCT for SCD has proven that eliminating the beta(S)-globin
      gene is curative when the transfer is stable. Thus replacement gene therapy for
      sickle cell disease remains a subject of intense interest and investigation.

PMID- 16304362
TI  - Hereditary periodic fever syndromes.
AB  - The hereditary periodic fevers are a group of Mendelian disorders characterized
      by seemingly unprovoked fever and localized inflammation. Recent data indicate
      that these illnesses represent inborn errors in the regulation of innate
      immunity. Pyrin, the protein mutated in familial Mediterranean fever, defines an
      N-terminal domain found in a large family of proteins involved in inflammation
      and apoptosis. Through this domain pyrin may play a role in the regulation of
      interleukin (IL)-1beta, nuclear factor (NF)-kappaB, and leukocyte apoptosis.
      Cryopyrin/NALP3, another protein in this family, is mutated in three other
      hereditary febrile syndromes and participates in the inflammasome, a newly
      recognized macromolecular complex crucial to IL-1beta activation. Somewhat
      unexpectedly, mutations in the 55 kDa receptor for tumor necrosis factor also
      give rise to a dominantly inherited periodic fever syndrome, rather than
      immunodeficiency, a finding that has stimulated important investigations into
      both pathogenesis and treatment. Finally, the discovery of the genetic basis of
      the hyperimmunoglobulinemia D with periodic fever syndrome suggests an as yet
      incompletely understood connection between the mevalonate pathway and the
      regulation of cytokine production. These insights extend our understanding of the
      regulation of innate immunity in man, while providing the conceptual basis for
      the rational design of targeted therapies, both for the hereditary periodic
      fevers themselves and other inflammatory disorders as well.

PMID- 16304363
TI  - Familial and acquired hemophagocytic lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition
      characterized by uncontrolled hyperinflammation on the basis of various inherited
      or acquired immune deficiencies. Cardinal symptoms are prolonged fever,
      hepatosplenomegaly and cytopenias. Central nervous system (CNS) symptoms are
      common. Biochemical markers include elevated triglyceride and ferritin, high
      levels of the alpha chain of the soluble interleukin-2 receptor and low
      fibrinogen. Impaired function of natural killer (NK) cells and cytotoxic T-cells
      (CTL) is a characteristic of all forms of HLH. Genetic HLH occurs in familial
      forms (FHLH), in which HLH is the primary and only manifestation, and in
      association with the immune deficiencies Chediak-Higashi syndrome (CHS),
      Griscelli syndrome (GS) and X-linked lymphoproliferative syndrome (XLP), in which
      secondary HLH occurs sporadically. Most patients with acquired HLH have no known
      underlying immune deficiency. Both acquired and genetic forms are triggered by
      infections, mostly viruses, or other stimuli. HLH also occurs as a complication
      of rheumatic diseases (macrophage activation syndrome) and of malignancies. The
      recent discovery of several genetic defects causing FHLH as well as the
      identification of the genes responsible for CHS, GS and XLP have underscored the
      role of granule (perforin/granzymes)-mediated cytotoxicity in both the killing of
      infected cells and the termination of the immune response. The immediate aim of
      therapy is suppression of the increased inflammatory response by
      immunosuppressive/immunomodulatory agents and cytotoxic drugs. Genetic cases can
      only be cured with stem cell transplantation. Awareness of the clinical symptoms
      and of diagnostic criteria for HLH is crucial to starting life-saving therapy in
      time.

PMID- 16304364
TI  - Chronic granulomatous disease and other disorders of phagocyte function.
AB  - The analysis of specific gene defects in disorders of phagocyte function has shed
      light on important aspects of the innate immune response. Each disorder has
      distinctive features in the clinical presentation and characteristic microbial
      pathogens. Chronic granulomatous disease has been extensively studied both in
      patient series and in mouse models. New insights continue to be obtained
      regarding the role of the nicotinamide dinucleotide phosphate (NADPH) oxidase and
      related enzymes in host defense and other aspects of the inflammatory response,
      as well as optimal management of this disorder. Approaches based on hematopoietic
      stem cell transplantation and gene therapy offer promise for the future, but are
      still under investigation. Also briefly summarized are updates on newly described
      leukocyte adhesion defects and on inherited susceptibility to mycobacterial
      infection due to defects in interleukin (IL)-12 and interferon-gamma pathways.

PMID- 16304365
TI  - Bone marrow failure: a child is not just a small adult (but an adult can have a
      childhood disease).
AB  - Aplastic anemia may be inherited or acquired. The distinction between these lies
      not in the age of the patient, but in the clinical and laboratory diagnoses.
      Adult hematologists must consider adult presentations of the inherited disorders,
      in order to avoid incorrect management of their patients. Physicians for adult
      patients must also realize that children with inherited disorders now survive to
      transition into their care. The major inherited bone marrow failure syndromes
      associated with development of pancytopenia include Fanconi anemia, dyskeratosis
      congenita, Shwachman-Diamond syndrome, and amegakaryocytic thrombocytopenia. The
      ages at presentation are highly variable, but often include individuals of adult
      age who have previously undiagnosed Fanconi anemia or dyskeratosis congenita.
      Many of the genes responsible for these disorders have been identified (12
      Fanconi anemia genes, 3 dyskeratosis congenita genes, and 1 each for Shwachman
      Diamond syndrome and amegakaryocytic thrombocytopenia). A high index of suspicion
      and specific testing of children or adults with what appears to be acquired
      aplastic anemia may identify inherited disorders. Correct classification of
      patients with aplastic anemia of any age is mandatory for their appropriate
      management.

PMID- 16304366
TI  - Aplastic anemia: management of pediatric patients.
AB  - Aplastic anemia is a term describing the common findings of pancytopenia and
      marrow hypoplasia arising from a variety of disease states, including acquired
      aplastic anemia and a variety of congenital marrow failure states. The management
      of children with these disorders has been confounded by difficulties of
      diagnosis. The availability of molecular testing has assisted in partial
      resolution of this problem but has raised new issues, such as the potential of
      genetic predisposition and the management of asymptomatic individuals with
      molecular markers. Longitudinal data from large cohort studies and disease
      registries are providing a rational basis for making more informed treatment
      decisions for children with these disorders. In particular, the ability to subset
      patients more accurately has improved triage of treatments. Approaches to
      hematopoietic stem cell transplantation (SCT), using both conventional and
      alternative donors, are changing rapidly, and the long-term sequelae of newer
      approaches are not entirely clear. Improved diagnosis and longer survival have
      fostered an understanding of the multidisciplinary approach necessary to manage
      both the underlying problems and the significant sequelae of treatment in both
      acquired and congenital disease.

PMID- 16304367
TI  - Aplastic anemia: management of adult patients.
AB  - The primary therapeutic approach to acquired aplastic anemia (AA) in older adults
      differs from the primary approach used in children and younger adults because in
      the former group, the results of allogeneic bone marrow transplantation (BMT) are
      less favorable. With increasing age of the patients, immunosuppressive therapy
      with antithymocyte globulin (ATG) and cyclosporine (CsA) constitutes the primary
      treatment option and may be better than BMT. There are very few clinical clues as
      to the selection of patients likely to respond to immunosuppression. Repeated
      ATG/CsA cycles are often used as salvage regimens, but in refractory patients BMT
      may be the best treatment option, as the prognosis for non-responders is poor
      without definitive treatment. Conservative therapy such as intense
      immunosuppression is associated with a high relapse rate but does not impact the
      survival and overall prognosis. The inability to eliminate autoimmune T cell
      clones using current therapeutic strategies suggests that prolonged
      immunosuppressive maintenance therapy may be needed for a substantial proportion
      of patients. Late clonal complications of conservatively treated patients include
      evolution to myelodysplasia and paroxysmal nocturnal hemoglobinuria and may
      develop in 20% of the patients. However, BMT also has several sequelae including
      an increased frequency of solid tumors. Novel immunosuppressive and
      immunomodulatory agents and constantly improving results of allogeneic BMT will
      further improve the survival rate of adult patients with AA.

PMID- 16304368
TI  - Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia.
AB  - Philadelphia chromosome positive (Ph(+)) acute lymphoblastic leukemia (ALL)
      includes at least one-quarter of all adults with ALL. Until recently,
      conventional chemotherapy programs that have been effective in other precursor B
      cell ALL cases have been unable to cure patients with this diagnosis. Allogeneic
      stem cell transplantation early in first remission has been the recommended
      therapy. The availability of imatinib mesylate and other tyrosine kinase
      inhibitors and small molecules that affect the BCR/ABL signaling pathways may be
      changing the treatment paradigm and the prognosis for these patients. The results
      from clinical trials using imatinib in the frontline setting and in relapsed
      patients as well as preliminary experience treating imatinib-resistant Ph(+) ALL
      will be described.

PMID- 16304369
TI  - The treatment of adolescents and young adults with acute lymphoblastic leukemia.
AB  - Intensive chemotherapy regimens for children with acute lymphoblastic leukemia
      (ALL) have greatly improved, and the majority of children with precursor B-cell
      ALL are able to achieve a complete remission (CR), with an induction rate
      approaching 98% and a 5-year estimated event-free survival rate (EFS) of
      approximately 80%. Although there have been dramatic improvements over the last
      several decades in both the EFS and overall survival (OS) rates in young children
      with ALL, the results in adult clinical trials have not kept pace. Current adult
      treatment regimens result in CR rates in the 80% range, with EFS at 5 years of
      only 30%-40%. Adolescents and young adults represent a minority of patients
      enrolled onto either adult or pediatric clinical trials. As a result, little
      information is available regarding CR, EFS, and OS rates for this age group, and
      the appropriate treatment regimen for this group of patients remains elusive.
      Recent studies suggest that young adult patients have far superior outcomes when
      treated on more intensive pediatric regimens. In addition, new insights into the
      molecular pathogenesis of T cell ALL have led to new therapeutic strategies.

PMID- 16304370
TI  - Acute lymphoblastic leukemia: older patients and newer drugs.
AB  - Although the median age for adults with acute lymphoblastic leukemia (ALL) is
      older than 60 years, relatively few of these patients have been enrolled on
      prospective clinical trials. The presence of coexisting medical disorders and
      unfavorable cytogenetic and biological characteristics within this population
      presents considerable challenges for successful treatment using conventional
      chemotherapy programs. Selected patients have achieved remission and long-term
      survival following intensive chemotherapy. Preliminary data using several new
      agents that have shown promise for patients with ALL are described.

PMID- 16304371
TI  - The molecular pathology of acute myeloid leukemia.
AB  - The pathogenesis of acute myelogenous leukemia (AML) involves an array of
      molecular alterations that disrupt almost every facet of cell transformation.
      These processes include the regulation of cell proliferation, differentiation,
      self-renewal, survival, cell cycle checkpoint control, DNA repair and chromatin
      stability, and cell dissemination. Normal regulatory networks are disrupted or
      usurped by these leukemogenic insults, and the understanding of these alterations
      is guiding the design of new therapeutic strategies. This overview describes some
      of the critical molecular alterations and implicates the rogue leukemogenic
      proteins in the onset and progression of AML.

PMID- 16304372
TI  - New strategies for the treatment of acute myeloid leukemia including antibodies
      and other novel agents.
AB  - The prognosis for younger adults (< or = 55-60 years) with acute myeloid leukemia
      (AML) has improved during the last four decades. However, there has been little
      progress in the treatment of older adults. This disappointing observation is
      important because the median age of patients with AML is about 70 years.
      Approximately 60%-80% of younger adults with AML achieve complete remission (CR)
      with the cytotoxic agents cytarabine and an anthracycline such as daunorubicin or
      idarubicin or the anthracenedione mitoxantrone. However, only 30%-40% of such
      patients are alive and disease-free at 5 years. Among older adults, CR is
      achieved in 40%-55%, but there are very few long-term survivors. Many studies
      have evaluated the impact of alternative doses and schedules, as well as
      additional cytotoxic drugs, on the prognosis for this group of patients. The
      outcome has not improved substantially beyond that achieved with conventional
      doses of an anthracycline and cytarabine followed by high-dose cytarabine
      consolidation.Several factors identified at diagnosis can predict outcome. The
      most important of these is the karyotype of the leukemic cells. Another critical
      factor is the presence of transmembrane transporter proteins, which confer
      multidrug resistance and mutations in or overexpression of specific genes such as
      WT1, C/EBPalpha, BAX, and BCL-2/BAX ratio, BAALC, EVI1, KIT and FLT3. The
      development of specific agents directed at gene mutations, signal transduction
      pathways and unique cell surface antigens provide the foundation for new
      therapeutic strategies. Such agents include the immunoconjugate gemtuzumab
      ozogamicin, multidrug resistance inhibitors, farnesyltransferase inhibitors,
      histone deacetylase and proteosome inhibitors, antiangiogenesis agents, FLT3
      inhibitors, apoptosis inhibitors, and nucleoside analogs. All of these agents can
      potentially address the heterogeneous abnormalities in AML and significantly
      improve the outcome for patients.

PMID- 16304373
TI  - Role of allogeneic stem cell transplantation in current treatment of acute
      myeloid leukemia.
AB  - Allogeneic hematopoietic stem cell transplantation (alloSCT) has been established
      as an effective consolidation therapy in acute myeloid leukemia (AML) in first or
      subsequent remission. Although it effectively prevents relapse, treatment-related
      mortality (TRM) associated with alloSCT may compromise that beneficial effect. As
      a result, alloSCT may be restricted to patients with a relatively high risk of
      relapse. Here, we review studies that identify categories of AML patients who may
      specifically benefit from alloSCT. In addition, we discuss recent developments
      with respect to alternative donors, stem cell sources, and supportive care.
      Finally, we highlight recent results obtained with reduced-intensity alloSCT,
      which already significantly influence our therapeutic strategy in elderly
      patients with AML.

PMID- 16304374
TI  - Molecular Pathogenesis of MDS.
AB  - Clonal disorders of hematopoiesis, such as myelodysplastic syndromes (MDS) and
      myeloproliferative diseases (MPD), affect both hematopoietic stem cells and
      progenitor cells within the erythroid, platelet and granulocytic lineages and can
      have devastating consequences in children and adults. The genetic features of
      these diseases often include clonal, nonrandom chromosomal deletions (e.g., 7q-,
      5q-, 20q-, 6q-, 11q- and 13q-) that appear to inactivate tumor suppressor genes
      required for the normal development of myeloid cells (reviewed in Bench and
      Fenaux). These putative tumor suppressors have proved to be much more difficult
      to identify than oncogenes activated by chromosomal translocations, the other
      major class of chromosomal lesions in MDS and MPD. Although MDS and MPD are
      almost certainly caused by mutations in stem/progenitor cells, the role of
      inactivated tumor suppressor genes in this process remains poorly understood. In
      a small portion of myeloid diseases, mutations have been identified in genes
      encoding factors known to be required for normal hematopoiesis, such as PU.1,
      RUNX1, CTNNA1 (alpha-catenin) and c/EBPalpha, and implicating these genes as
      tumor suppressors. Nonetheless, the identities of most deletion-associated tumor
      suppressors in these diseases remains elusive, despite complete sequencing of the
      human genome. The deleted regions detected by cytogenetic methods are generally
      very large, containing many hundreds of genes, thus making it hard to locate the
      critical affected gene or genes. It is also unclear whether dysfunctional
      myelopoiesis results from haploinsufficiency, associated with the deletion of one
      allele, or from homozygous inactivation due to additional point mutations or
      microdeletions of the retained wild-type allele. In general MDS have proved
      surprisingly resistant to conventional treatments. Targeted therapeutic advances
      in MDS will likely depend on a full comprehension of underlying molecular
      mechanisms, in particular the tumor suppressor genes lost through clonal,
      nonrandom chromosomal deletions, such as the 7q- and (del)5q.

PMID- 16304375
TI  - Update on supportive care and new therapies: immunomodulatory drugs, growth
      factors and epigenetic-acting agents.
AB  - Patients with "low-risk" myelodysplastic syndrome (MDS) are mostly treated with
      approaches aiming to reduce the negative consequences of ineffective
      hematopoiesis. Transfusion therapy should be tailored to allow adequate
      oxygenation and optimal quality of life, and may lead to the need for iron
      chelation therapy. Growth factors (erythropoietin and granulocyte colony
      stimulating factor [G-CSF]) may induce long-lasting improvement of hemoglobin
      levels and does not increase the risk for leukemic transformation. Growth factors
      should be offered to defined subgroups of patients. Immunosuppression with anti
      thymoglobulin or cyclosporine A may be an alternative for younger patients with
      refractory anemia (RA). The new immunomodulating compound lenalidomide, CC5013,
      is very active in the 5q- syndrome and is under evaluation for other low-risk MDS
      subtypes. "High-risk" MDS is associated with poor survival and high risk for
      leukemic transformation. The DNA hypomethylating compounds azacytidine and
      decitabine may offer improved long-term outcomes in this group of patients,
      although there has so far been no effect on survival rates. The efficacy of
      farnesyl transferase inhibitors has been evaluated in a series of phase II
      trials. The overall response rate was low, but the majority of responses were
      CRs. Finally, a number of new drugs directed to various biological and genetic
      targets are entering clinical trials.

PMID- 16304376
TI  - Optimization of transplant regimens for patients with myelodysplastic syndrome
      (MDS).
AB  - Myelodysplastic syndrome (MDS) is a hemopoietic stem cell disorder that is
      potentially curable by transplantation of normal hemopoietic stem cells. The
      optimum timing, however, and the best conditioning strategy have remained
      controversial. Both conventional and reduced-intensity/nonmyeloablative regimens
      have been used successfully. Among selected patients with less advanced/low-risk
      MDS (< 5% marrow myeloblasts), 3-year survivals of 65% to 75% are achievable with
      HLA-matched related and unrelated donors. Among patients with more advanced/ high
      risk disease (> or = 5% marrow blasts; high International Prognostic Scoring
      System [IPSS] scores), the probability of post-transplant relapse ranges from 10%
      to 40%, and, as a result, relapse-free survival is inferior. In addition to
      disease stage, co-morbid conditions, pre-transplant chemotherapy, conditioning
      regimen, source of stem cells, and post-transplant immunosuppression affect
      transplant outcome. Reduced-intensity conditioning regimens are associated with a
      decrease in non-relapse mortality and allow for successful hemopoietic stem cell
      transplants even in patients 60-70 years of age. Graft-versus-host disease, both
      acute and chronic, and post-transplant relapse remain challenging problems.

PMID- 16304377
TI  - Management of early stage disease.
AB  - More than 80% of newly diagnosed patients with chronic myeloid leukemia in
      chronic phase will achieve a complete cytogenetic response (CCR) with the
      standard dose of 400 mg imatinib daily. The probability of progression free
      survival is tightly correlated with the level of response, approaching 100% in
      those patients who achieve a reduction of BCR-ABL mRNA by at least 3-log at 12
      months. High Sokal risk predicts poorer outcome, but on-treatment response
      parameters generally override pretherapeutic prognostic variables. Standard
      disease monitoring includes full blood counts, cytogenetics and quantitative RT
      PCR for BCR-ABL mRNA but must be tailored to the level of response attained by a
      given patient. Conservative therapeutic milestones include a complete hematologic
      response at 3 months, a minor cytogenetic response at 6, a major cytogenetic
      response at 12 and CCR at 18, but a more aggressive approach may be justified in
      specific circumstances. Failure to achieve any of these milestones should trigger
      a re-assessment of the therapeutic strategy. Most patients with CCR remain
      positive by RT-PCR, and discontinuation of drug is usually followed by relapse,
      suggesting that imatinib fails to eradicate leukemic stem cells. The mechanisms
      underlying disease persistence are not well understood. Evidence is accumulating
      that early therapy intensification using high doses of imatinib (800 mg daily) or
      imatinib in combination with cytarabine or interferon-alpha may induce higher
      rates of RT-PCR negativity. Large studies will be required to determine whether
      this translates into improved progression free and overall survival.

PMID- 16304378
TI  - Loss of response to imatinib: mechanisms and management.
AB  - The treatment of chronic myeloid leukemia (CML) has been revolutionized by the
      small molecule BCR-ABL-selective kinase inhibitor imatinib. Although imatinib is
      highly effective initially and generally well-tolerated, relapse is increasingly
      encountered clinically. Until recently, for the majority of CML patients with
      disease no longer responsive to imatinib, as well as for patients with imatinib
      intolerance, few effective therapeutic options existed. Our understanding of the
      major mechanisms of imatinib resistance has led to the clinical development of
      two novel BCR-ABL inhibitors that harbor significant therapeutic promise in early
      clinical trial experience. These agents, dasatinib (BMS-354825) and AMN107, are
      more potent inhibitors of BCR-ABL than imatinib, and moreover, harbor activity
      against nearly all imatinib-resistant BCR-ABL kinase domain mutant forms tested
      in vitro. Notably, neither of these compounds is effective against the imatinib
      resistant BCR-ABL/T315I mutation. The potential availability of highly effective
      medications for the treatment of imatinib-resistant and intolerant cases of CML
      is expected to further complicate the timing of other effective therapies, such
      as allogeneic stem cell transplantation. Additionally, periodic genotyping of the
      BCR-ABL kinase domain to screen for drug-resistant mutations may play an
      increasingly important role in the future management of CML cases.

PMID- 16304379
TI  - Pathobiology of lymphoid and myeloid blast crisis and management issues.
AB  - Despite recent improvements in the treatment of early-stage disease, the blastic
      phase of chronic myeloid leukemia (CML) remains a therapeutic challenge. For
      imatinib-naive patients, imatinib provided encouraging hematologic and
      cytogenetic benefits; however, the vast majority of CML blast crisis cases today
      arise in patients already on imatinib-based therapy. Clonal evolution and
      duplication of the Philadelphia chromosome continue to be associated with blastic
      phase transformation, but recent studies have identified BCR/ABL kinase domain
      mutations in 30%-40% of blast crisis patients. This implies that BCR-ABL-targeted
      therapy might have influenced the molecular road map to blastic transformation.
      In this review, we will examine the effect of imatinib on primitive CML
      progenitors and how this might influence the pathophysiology of blast crisis. A
      rational framework for deciding how best to integrate stem cell transplantation,
      traditional chemotherapy, imatinib, and other BCR-ABL kinase inhibitors in the
      care of blast crisis patients will also be discussed.

PMID- 16304380
TI  - A unique activating mutation in JAK2 (V617F) is at the origin of polycythemia
      vera and allows a new classification of myeloproliferative diseases.
AB  - Myeloproliferative disorders (MPDs) are heterogeneous diseases that occur at the
      level of a multipotent hematopoietic stem cell. They are characterized by
      increased blood cell production related to cytokine hypersensitivity and
      virtually normal cell maturation. The molecular pathogenesis of the MPDs has been
      poorly understood, except for chronic myeloid leukemia (CML), where the Bcr-Abl
      fusion protein exhibits constitutive kinase activity. Since some rare MPDs are
      also related to a dysregulated kinase activity, a similar mechanism was thought
      to be likely responsible for the more frequent MPDs. We investigated the
      mechanisms of endogenous erythroid colony formation (EEC) by polycythemia vera
      (PV) erythroid progenitor cells and found that EEC formation was abolished by a
      pharmacological inhibitor of JAK2 as well as an siRNA against JAK2. JAK2
      sequencing revealed a unique mutation in the JH2 domain leading to a V617F
      substitution in more than 80% of the PV samples. This mutation in the
      pseudokinase autoinhibitory domain results in constitutive kinase activity and
      induces cytokine hypersensitivity or independence of factor-dependent cell lines.
      Retroviral transduction of the mutant JAK2 into murine HSC leads to the
      development of an MPD with polycythemia. The same mutation was found in about 50%
      of patients with idiopathic myelofibrosis (IMF) and 30% of patients with
      essential thrombocythemia (ET). Using different approaches, four other teams have
      obtained similar results. The identification of the JAK2 mutation represents a
      major advance in our understanding of the molecular pathogenesis of MPDs that
      will likely permit a new classification of these diseases and the development of
      novel therapeutic approaches.

PMID- 16304381
TI  - Management of polycythemia vera and essential thrombocythemia.
AB  - The optimal management of patients with polycythemia vera (PV) and essential
      thrombocythemia (ET) continues to be controversial. Both diseases present
      diagnostic challenges and there is a paucity of data from randomized clinical
      trials to guide therapeutic decisions. However, the past two years have seen
      major advances in our understanding of these myeloproliferative disorders (MPD).
      First, the ECLAP study demonstrated the anti-thrombotic efficacy of aspirin in
      patients with PV. Second, the PT-1 trial, the largest randomized study of any
      MPD, has provided much needed guidance on the optimal management of patients with
      ET. Third, the identification of a single JAK2 mutation in most patients with PV,
      and in some of those with ET, illuminates the pathogenesis of these diseases and
      raises questions about the boundary between them. For the purpose of management
      decisions, it remains appropriate to consider them as separate entities for the
      time being. However, as we learn more about the clinical significance of the JAK2
      mutation, it seems likely that the coming years will see major changes in the way
      we classify and manage these disorders.

PMID- 16304382
TI  - Recent advances in the diagnosis and treatment of hypereosinophilic syndromes.
AB  - Hypereosinophilic syndromes (HES) are a heterogeneous group of disorders
      characterized by marked peripheral blood and tissue eosinophilia resulting in end
      organ damage. Recent advances in molecular biology and immunology have led to the
      identification of a number of distinct subtypes of HES with differing
      epidemiology, pathogenesis, and prognosis. The ability to distinguish between
      these HES subtypes combined with the availability of new treatment modalities,
      including tyrosine kinase inhibitors and monoclonal antibodies, that target
      specific molecules involved in disease pathogenesis have dramatically altered the
      approach to the diagnosis and treatment of HES.

PMID- 16304383
TI  - Targeting the IAP family of caspase inhibitors as an emerging therapeutic
      strategy.
AB  - The IAPs (inhibitor of apoptosis proteins) are a family of caspase inhibitors
      that block the execution phase of apoptosis. Overexpression of IAPs confers
      chemoresistance and, in some groups of patients, is associated with a poor
      prognosis. Given their role in the development and progression of solid tumors
      and hematologic malignancies, efforts are underway to develop therapeutic IAP
      inhibitors, with a focus on X-linked IAP (XIAP) and survivin. Antisense
      oligonucleotides that target XIAP and survivin have been developed and are
      currently in phase I clinical trial. Small-molecules that bind and inhibit XIAP
      have also been identified and are in the process of clinical development. This
      review focuses on the preclinical data that support the development of IAP
      targeted therapies.

PMID- 16304385
TI  - Modulating the bcl-2 family of apoptosis suppressors for potential therapeutic
      benefit in cancer.
AB  - Members of the BCL-2 family of proteins regulate and execute many cell intrinsic
      apoptosis pathways, including those arising from dysregulated expression of
      cellular oncogenes. Since pro-survival members of the family are often strongly
      elevated in diverse cancers, with the potential to confer resistance to both
      endogenous cell death stimuli and many cancer treatments, there has been intense
      interest to develop strategies to therapeutically modulate their activity.
      Although encouraging genetic and pharmacological preclinical proof of concept has
      been obtained, the challenge for clinical development will be to devise
      strategies that address the fact that multiple pro-survival members are typically
      up-regulated in a given cancer and the family operates primarily through protein
      protein interactions. Moreover, since several current therapies themselves are
      known to stimulate the levels of one or more family members, there will be
      additional challenges (and opportunities) in exploiting this target in the
      clinic. In this review, we describe the rationale for targeting the BCL-2 family
      of apoptosis suppressors in cancer and the progress that has been made in
      modulating the family by small molecule antagonists.

PMID- 16304384
TI  - The ubiquitin proteasome pathway from bench to bedside.
AB  - The validation of the ubiquitin-proteasome pathway as a target for therapy of
      hematological malignancies stands out as one salient example of the ability to
      translate laboratory-based findings from the bench to the bedside. Preclinical
      studies showed that proteasome inhibitors had significant activity against models
      of non-Hodgkin lymphoma and multiple myeloma, and identified some of the relevant
      mechanisms of action. These led to phase I through III trials of the first
      clinically available proteasome inhibitor, bortezomib, which confirmed its
      activity as a single agent in these diseases. Modulation of proteasome function
      was then found to be a rational approach to achieve both chemosensitization in
      vitro and in vivo, as well as to overcome chemotherapy resistance. Based on these
      findings, first-generation bortezomib-based regimens incorporating traditional
      chemotherapeutics such as alkylating agents, anthracyclines, immunomodulatory
      agents, or steroids have been evaluated, and many show promise of enhanced
      clinical anti-tumor efficacy. Further studies of the pro-and anti-apoptotic
      actions of proteasome inhibitors, and of their effects on gene and protein
      expression profiles, suggest that novel agents, such as those targeting the heat
      shock protein pathways, are exciting candidates for incorporation into these
      combinations. Phase I trials to test these concepts are just beginning, but have
      already shown some encouraging results. Finally, novel proteasome inhibitors are
      being developed with unique properties that may also have therapeutic
      applications. Taken together, these studies demonstrate the power of rational
      drug design and development to provide novel, effective therapies for patients
      with hematological malignancies.

PMID- 16304386
TI  - Immunobiology and pathophysiology of Hodgkin lymphomas.
AB  - Classical Hodgkin lymphoma (HL) is characterized by the presence of Reed
      Sternberg (RS) cells, which are transformed post-germinal center B cells destined
      for apoptosis since they have not undergone successful immunoglobulin gene
      rearrangement. Several mechanisms, including latent infection by Epstein-Barr
      virus (EBV), allow these cells to survive. It is remarkable that many of the
      signaling pathways that promote survival are shared between the EBV-induced
      proteins, such as EBNA1, LMP1, and LMP2, and other molecules that are upregulated
      in RS cells. A key role is played by the presence of constitutive nuclear factor
      (NF)-kappaB, which is induced by LMP1, as well as by CD30, CD40, tumor necrosis
      factor (TNF)-alpha, and Notch1 interactions, and results in the upregulation of
      at least 45 genes including chemokines, cytokines, receptors, apoptotic
      regulators, intracellular signaling molecules, and transcription factors. The
      other characteristic of classical HL is the presence of an extensive inflammatory
      infiltrate. Key features of this infiltrate are that it comprises Th2 and T
      regulatory cells and generally lacks Th1 cells, CD8 cytotoxic T cells, and
      natural killer (NK) cells. The RS cells appear to induce this infiltrate by the
      secretion of Th2 type chemokines such as TARC and MDC. The RS cells also produce
      cytokines that inhibit Th1 responses, as interleukin (IL)-10 and transforming
      growth factor (TGF)-beta express CD95 ligand, which induces apoptosis of
      activated Th1 and CD8 T cells. Other important mechanisms that allow the RS cells
      to escape an effective anti-EBV immune response include the downregulation of HLA
      class I in EBV-negative cases or the presence of a polymorphism in HLA class I in
      EBV-positive cases that allow escape from CD8-mediated cytotoxicity. On the other
      hand, expression of HLA-G allows the escape from NK cells that would normally
      recognize the HLA class I-negative RS cells. Overall, the cellular infiltrate in
      HL appears to play a decisive role in allowing the RS cells to survive by
      providing an environment that suppresses cytotoxic immune responses and providing
      cellular interactions and cytokines that support the growth and survival of RS
      cells. Future therapeutic strategies could focus directly on the NF-kappaB
      activation, on various receptors to ligand interactions, on the chemokine and
      cytokine network, or on the induction of effective anti-EBV latent protein immune
      responses.

PMID- 16304387
TI  - Evolving approaches to primary treatment of Hodgkin lymphoma.
AB  - Two challenges confront the clinician treating Hodgkin lymphoma today: achieving
      a high level of effectiveness while minimizing toxicity. At least 80% of patients
      can be cured with currently available chemotherapy regimens, augmented in
      selected patients with the addition of involved field radiation or intensified
      chemotherapy assisted by granulocyte growth factors or stem cell transplantation.
      Major late toxicity including infertility, premature menopause, cardiovascular
      disease and second neoplasms can be avoided in most patients if the treatment
      program is chosen carefully. The extent of disease (stage) and, for advanced
      stage lymphoma, the presence of well-characterized prognostic factors can be
      established with readily available clinical, laboratory and imaging techniques.
      Results from carefully designed and analyzed clinical trials have identified
      optimal treatment approaches for patients with limited and advanced stage
      disease. Those with limited stage Hodgkin lymphoma should be treated with brief
      chemotherapy, only augmented with involved field irradiation if an early complete
      remission is not achieved. Most patients with advanced stage lymphoma can be
      cured with an extended course of ABVD (doxorubicin, bleomycin, vinblastine and
      dacarbazine). The small minority under the age of 60 years with an International
      Prognostic Factors Project score of 5 or greater should be considered for
      intensified chemotherapy. Patients known to have bulky tumor(s) (> 10 cm) at
      diagnosis may require adjuvant irradiation at the conclusion of chemotherapy, but
      its utility has not been unequivocally established and radiation should be
      avoided in those who achieve a complete remission, where it is known to be
      ineffective. With careful selection of treatment program most patients found to
      have Hodgkin lymphoma today can be offered a high probability of cure and a low
      likelihood of major late toxicity. However, without detailed attention to the
      extent of lymphoma and other prognostic factors, there is as much danger of over
      treatment as under-treatment. Only by thoughtfully adjusting the treatment
      program to the extent of disease and response to treatment can the clinician
      determine the optimal approach, maximizing likelihood of cure and minimizing late
      toxicity.

PMID- 16304388
TI  - Therapies for relapsed Hodgkin lymphoma: transplant and non-transplant approaches
      including immunotherapy.
AB  - Autologous stem cell transplant remains the standard of care for relapsed Hodgkin
      lymphoma (HL). Approximately 50% of patients with chemo-sensitive relapse will be
      cured with this approach. The optimal pretransplant salvage regimen is
      controversial, but less toxic combinations seem to be equivalent to more
      aggressive approaches. For patients with chemo-refractory disease at relapse and
      those failing autologous transplant, the long-term prognosis remains poor. New
      approaches such as reduced-intensity allogeneic transplant, monoclonal antibodies
      targeting the CD30 antigen, Epstein-Barr virus (EBV)-specific cytotoxic T
      lymphocytes, and bortezomib are under investigation, but preliminary results are
      disappointing. New therapies are needed for patients with relapsed HL.

PMID- 16304389
TI  - Diffuse large B-cell lymphoma: risk stratification and management of relapsed
      disease.
AB  - The clinical factors described by the International Prognostic Index (IPI)
      provide a model for risk stratification in diffuse large B-cell lymphomas
      (DLBCLs). However, there is variability in outcome within IPI risk groups,
      indicating the biological and clinical heterogeneity of these diseases. Studies
      of gene expression profiling (GEP) in DLBCL are uncovering biological
      heterogeneity with prognostic significance. Various gene expression signatures
      with predictive value independent of the IPI are now recognized. Immunophenotypic
      features of DLBCL have also been shown to have prognostic value. The use of
      fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning may provide
      additional predictive information when used at diagnosis or soon after initiation
      of treatment. Future prognostic models in DLBCL are likely to incorporate
      functional imaging, immunophenotype and GEPs as well as clinical data in risk
      stratification and choice of treatment. Treatment of relapsed DLBCL remains a
      major problem. High-dose therapy (HDT) and stem cell transplantation (SCT) has
      been shown to produce superior overall survival (OS) compared with conventional
      dose salvage therapy in patients with relapsed, chemosensitive DLBCL. However,
      only 20% to 30% of patients are cured by this approach, and the effectiveness of
      HDT and SCT in patients treated with rituximab-based combinations as first-line
      therapy is unknown. Although new transplant techniques including non
      myeloablative allogeneic SCT are being investigated, their role is unclear. New
      treatment strategies are needed for these patients. The use of molecular
      techniques such as GEP is identifying many potential new therapeutic targets in
      DLBCL including histone deacetylase, HLA-DR, bcl-2, bcl-6, mTOR and TRAIL.

PMID- 16304390
TI  - Biology and treatment of Epstein-Barr virus-associated non-Hodgkin lymphomas.
AB  - Epstein-Barr virus (EBV) is associated with several different types of aggressive
      non-Hodgkin lymphoma (NHL). Individuals with primary or secondary
      immunodeficiency are susceptible to developing B cell lymphoproliferation due to
      outgrowth of EBV-infected B cells that express type III latency characterized by
      expression of all nine latent-cycle EBV antigens. These cells would normally be
      susceptible to control by EBV-specific T cells, and strategies to restore EBV
      specific immune responses may be effective therapeutically. EBV-associated
      lymphomas occurring in individuals who do not have a known immunodeficiency
      include NK and T malignancies with cytotoxic phenotypes, sporadic cases of B-NHL
      and lymphomatoid granulomatosis. These malignancies respond poorly to standard
      chemoradiotherapy, and immunotherapeutic or pharmacologic strategies targeting
      EBV are being explored.

PMID- 16304391
TI  - Aggressive peripheral T-cell lymphomas (specified and unspecified types).
AB  - Peripheral T-cell lymphomas (PTCLs) are a biologically diverse and uncommon group
      of diseases. Compared to their B-cell counterparts, PTCLs remain largely
      unexplored and the optimal treatment ill-defined due to disease rarity and
      biological heterogeneity. For the majority of PTCL subtypes, prognosis is poor
      with a 5-year overall survival of approximately 30% in most series.The notable
      exception is ALK-positive anaplastic large-cell lymphoma (ALK-pos ALCL), which
      has a superior outcome. The international prognostic index can be used to some
      extent to define risk groups within some PTCL subtypes, including PTCL
      unspecified (PTCLUS). It is likely that the observed clinical heterogeneity
      reflects differences at the molecular level. With the more widespread
      availability of gene expression profiling, it may be possible in the future to
      further refine the classification of PTCLs and elucidate novel therapeutic
      targets. Future clinical trials are needed that focus specifically on PTCL to
      advance our understanding and define the optimal management in this disease.

PMID- 16304392
TI  - CLL biology and prognosis.
AB  - Chronic lymphocytic leukemia (CLL) follows an extremely variable course with
      survival ranging from months to decades. Recently, there has been major progress
      in the identification of molecular and cellular markers that may predict the
      tendency for disease progression in CLL patients. In particular, the mutational
      profile of Ig genes and some cytogenetic abnormalities have been found to be
      important predictors of prognosis in CLL. However, this progress has raised new
      questions about the biology and prognosis of the disease, some of which are
      addressed here. Such questions include: 1) What is the role of the B-cell
      receptor (BCR) in CLL pathogenesis? 2) Is CLL one disease? 3) Is CLL an
      accumulative disease? 4) What is the normal counterpart of the CLL B lymphocyte?
      5) Have the Rai and Binet staging systems become obsolete? 6) Which is the best
      surrogate for Ig mutational profiles?

PMID- 16304393
TI  - Chronic lymphocytic leukemia (CLL): first-line treatment.
AB  - For the past ten years, there has been a dynamic development of new therapeutic
      compounds and prognostic parameters for chronic lymphocytic leukemia (CLL).
      Hematologists and oncologists are challenged to use these new possibilities for
      an optimized, risk- and fitness-adapted treatment strategy, with the goal of
      achieving long-term remissions and preserving a good quality of life. This review
      is intended to summarize the current knowledge on first-line treatment of CLL.

PMID- 16304394
TI  - Salvage therapy for CLL and the role of stem cell transplantation.
AB  - Chronic lymphocytic leukaemia (CLL) remains an incurable disease and,
      notwithstanding the excellent remission rates now achieved with purine analogs
      and monoclonal antibodies, the vast majority of patients with CLL are destined to
      relapse after primary treatment. The management of relapsed CLL patients is then
      dependent upon a number of factors, most importantly age, performance status,
      previous therapy administered, the response and duration of response to such
      therapy, and time from last therapy. Although prior therapy and response to such
      therapy are important factors in determining next therapy, it is often difficult
      to determine their importance from published studies. Furthermore, the goal of
      therapy, whether palliative or aggressive, must also be weighed into the decision
      when deciding on the next line of treatment. With many potential treatments
      available, the sequence of treatments and the timing of procedures such as stem
      cell transplantation remain controversial and are the focus of ongoing clinical
      trials.

PMID- 16304395
TI  - Hematopathology approaches to diagnosis and prognosis of indolent B-cell
      lymphomas.
AB  - The advent of new technologies has contributed to improvements in the diagnosis
      and classification of the non-Hodgkin lymphomas (NHL). Use of a more extensive
      test menu of paraffin active monoclonal antibodies for immunohistochemistry,
      molecular cytogenetic studies including standard cytogenetics, multi-color
      fluorescence in-situ hybridization (FISH), polymerase chain reaction and locus
      specific FISH, as well as developments in high-resolution techniques including
      microarray gene expression profiling and array comparative genomic hybridization
      (CGH) allow more accurate diagnosis and precise definition of biomarkers of value
      in risk stratification. The identification of disease-specific gene lists
      resulting from expression profiling provides a number of potential protein
      targets that can be validated using immunohistochemistry. We will highlight how
      improvements in our understanding of lymphoma biology rapidly facilitate the
      development of new diagnostic reagents that could be used to alter clinical
      practice. These changing trends allow the development of new diagnostic
      strategies used to render accurate sub-classification of entities within the
      category of indolent B-cell lymphomas, including their distinction from related
      but more aggressive disorders, such as mantle cell lymphoma. A comprehensive
      understanding of the biology of these distinct lymphoid tumors will allow us to
      identify novel disease-related genes and should facilitate the development of
      improved diagnostics, outcome prediction, and personalized approaches to
      treatment.

PMID- 16304396
TI  - Clinical presentation and management of marginal zone lymphomas.
AB  - Marginal-zone lymphoma (MZL) includes three subtypes depending on the site of
      lymphoma involvement: extranodal marginal zone B-cell lymphoma of mucosa
      associated lymphoid tissue (MALT-lymphoma); splenic MZL; and nodal MZL. Beside a
      common cell-of-origin and similarities concerning a possible chronic antigenic
      stimulation by microbial pathogens and/or autoantigens, the clinical presentation
      is very different with symptoms related to lymphoma location. MALT and splenic
      MZL present with an indolent disease with good performance status, no B symptoms,
      and no adverse prognostic factors and are associated with long survival. Patients
      with nodal MZL present with a more aggressive disease and have a shorter failure
      free survival. Clinical and biological prognostic factors identified in reported
      series are heterogeneous. The optimal treatment has yet to be defined for the
      three subtypes, and current strategies will be described in this review.

PMID- 16304397
TI  - Biology and management of histologic transformation of indolent lymphoma.
AB  - The evolution of indolent lymphomas to aggressive histologies, known as
      histologic transformation (HT), is a frequent occurrence for all subtypes of low
      grade B cell lymphoproliferative disorders. The risk of developing HT is
      approximately 3% per year for patients with indolent lymphoma. Clinically these
      present with a rapid change in the behavior of the disease, with evidence of a
      highly proliferative malignancy with a propensity to involve extranodal sites.
      The prognosis of patients following transformation is generally poor, with median
      survival of about 12 months. Recent studies suggest that the development of HT is
      very complex with the acquisition of multiple cytogenetic abnormalities in the
      low-grade lymphoma cells prior to HT. To date, there are no biologic or genetic
      parameters predictive of the development of HT. A myriad of genetic lesions have
      been identified in HT, and provide insight into its pathogenesis. These include
      genes regulating proliferation (C-MYC and C-MYC-regulated genes); control of the
      cell cycle (CDKN2a and CDKN2B); and programmed cell death (TP53, C-MYC, and
      BCL2). Gene expression profiling has been applied to the study of HT and has
      increased our understanding of the transformation process. There has been limited
      progress in the treatment of patients with HT. Conventional chemotherapy is
      generally of limited benefit, although a subset of patients are long-term
      survivors following high-dose therapy and autologous stem cell transplantation.
      The use of radioimmunotherapy and new agents targeting specific lesions or
      aberrant pathways may impact on the management of these aggressive diseases.

PMID- 16304398
TI  - Multimodality therapies and optimal schedule of antibodies: rituximab in lymphoma
      as an example.
AB  - Rituximab was the first humanized antibody widely used on patients, so research
      on its optimal use was a clinical challenge. Many studies have been performed to
      optimize its dose and schedule, and more are ongoing. The dose of 375 mg/m(2) has
      become standard, mainly because it shows activity and has little associated
      toxicity. The combination of rituximab with chemotherapy has been shown to
      prolong remission in all types of lymphomas, and in patients with diffuse large B
      cell lymphoma it can improve survival. As a single agent, particularly when the
      treatment is prolonged over several months, results are similar to chemotherapy
      but with fewer side effects. Finally, used as maintenance therapy it can prolong
      the duration of chemotherapy-obtained remissions. Based on available data, the
      administration of 375 mg/m(2) before each chemotherapy cycle can be recommended
      for first line treatment of patients with curable B-cell lymphomas and for
      patients with high-risk indolent lymphoma who are rituximab-naive. Single-agent
      treatment at a prolonged schedule is recommended for cases of indolent disease
      not in need of urgent response and for patients who are unlikely to tolerate
      chemotherapy.

PMID- 16304399
TI  - Unique toxicities and resistance mechanisms associated with monoclonal antibody
      therapy.
AB  - Anti-CD20 therapy has had a truly dramatic impact on treatment and outcome of
      patients with follicular lymphoma. Unfortunately, the majority of responses to
      single-agent rituximab are incomplete, and all patients with follicular lymphoma
      will experience disease progression at some point following rituximab therapy.
      Rituximab has multiple mechanisms of inducing in vivo cytotoxicity, including
      antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity,
      direct apoptotic signaling, and possible vaccinal effects. The cellular
      microenvironment within follicular lymphoma has a profound impact on which
      mechanism is dominant, and confers resistance in many situations. Both tumor
      associated and host-associated factors also contribute to rituximab resistance.
      There are multiple potential approaches to overcoming rituximab resistance,
      including rational biologic combination immunotherapy, engineered antibodies, and
      radioimmunoconjugates. Improved ability to overcome resistance will require
      further elucidation of critical signaling pathways involved in rituximab induced
      cytotoxicity and a comprehensive understanding of interactions between its
      multiple mechanisms of action.

PMID- 16304400
TI  - Targeting CD20 in follicular NHL: novel anti-CD20 therapies, antibody
      engineering, and the use of radioimmunoconjugates.
AB  - Rituximab (chimeric anti-CD20 monoclonal antibody) is widely employed in the
      treatment of patients with B cell non-Hodgkin lymphoma (NHL). This agent has
      activity in both indolent and aggressive disease, alone and in combination with
      chemotherapy. Unfortunately, however, many patients develop resistant disease.
      Ongoing efforts to improve outcomes include changes in dose and schedule, as well
      as the use of other biologic agents or antibodies that may enhance activity when
      administered together with rituximab. A relatively new focus is the development
      of engineered anti-CD20 antibodies that are optimized for their capability to
      mediate antibody-mediated cellular cytotoxicity (ADCC) or complement-dependent
      cytotoxicity (CDC). Human or humanized structures have also been employed to
      potentially improve these attributes, as well as to improve on pharmacokinetics
      and immunogenicity. Other studies in NHL have clearly demonstrated that
      radiolabeled anti-CD20 antibodies (such as I-131 tositumomab and Y-90 ibritumomab
      tiuxetan) may be useful in relapsed and refractory disease, and have potential
      utility as part of initial treatment as well. Further studies of these modified
      anti-CD20 antibodies are ongoing in order to optimize their use for maximal
      clinical benefit.

PMID- 16304401
TI  - MGUS and smoldering multiple myeloma: update on pathogenesis, natural history,
      and management.
AB  - Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple
      myeloma (SMM) are asymptomatic, pre-malignant disorders characterized by
      monoclonal plasma cell proliferation in the bone marrow and absence of end-organ
      damage. Recent advances in the pathogenesis, natural history, and prognosis of
      MGUS and SMM are reviewed. A new risk stratification system to determine the
      prognosis of MGUS using the size and type of M protein, and the serum free light
      chain assay is discussed.

PMID- 16304402
TI  - Early genetic events provide the basis for a clinical classification of multiple
      myeloma.
AB  - Multiple myeloma is a tumor of somatically mutated, isotype-switched plasma cells
      that accumulate in the bone marrow leading to bone destruction and bone marrow
      failure. The germinal center processes of somatic hypermutation and switch
      recombination are implicated in the development of recurrent immunoglobulin gene
      translocations in 40% of patients. These affect five loci: 11q13, 6p21, 4p16,
      16q23 and 20q11, leading to dysregulation of CCND1, CCND2, FGFR3/MMSET, c-MAF and
      MAFB respectively. The remaining 60% of patients can be divided into four groups
      based on their expression of CCND1 and CCND2. The largest group (40%) ectopically
      express CCND1 bi-allelically and have hyperdiploidy with multiple trisomies of
      chromosomes 3, 5, 7, 9, 11, 15, 19 and 21. The translocation and cyclin D (TC)
      groups identify patients with different genetics, biology, clinical features,
      prognosis and response to therapy.

PMID- 16304403
TI  - An update of the management of multiple myeloma: the changing landscape.
AB  - The management of multiple myeloma is rapidly changing. Cytogenetic, molecular
      and proteomic techniques have led to a better understanding of the
      pathophysiology of this heterogeneous malignancy. Novel agents designed to
      interrupt myeloma growth and survival pathways have entered into clinical usage
      with unprecedented speed, while new prognostic systems based on clinical and
      biologic features, such as cytogenetic abnormalities, have been developed. A
      plethora of clinical trials have been initiated utilizing novel agents, alone or
      in conjunction with established modalities such as conventional cytotoxic agents
      and stem cell transplantation. These newer treatments have increased the
      antitumor response rates in this disease and have provided options for patients
      whose disease has become resistant to conventional therapy. A major challenge is
      to define the optimal use of these new agents and combinations in order to
      significantly impact the natural history of myeloma.

PMID- 16304404
TI  - POEMS Syndrome.
AB  - POEMS syndrome is defined by the presence of a peripheral neuropathy (P), a
      monoclonal plasma cell disorder (M), and other paraneoplastic features, the most
      common of which include organomegaly (O), endocrinopathy (E), skin changes (S),
      papilledema, edema, effusions, ascites, and thrombocytosis. Virtually all
      patients will have either sclerotic bone lesion(s) or co-existent Castleman's
      disease. Not all features of the disease are required to make the diagnosis, and
      early recognition is important to reduce morbidity. Other names for the syndrome
      include osteosclerotic myeloma, Crow-Fukase syndrome, or Takatsuki syndrome.
      Because the peripheral neuropathy is frequently the overriding symptom and
      because the characteristics of the neuropathy are similar to that chronic
      inflammatory demyelinating polyneuropathy (CIDP), patients are frequently
      misdiagnosed with CIDP or monoclonal gammopathy of underdetermined significance
      (MGUS)-associated peripheral neuropathy. Not until additional features of the
      POEMS syndrome are recognized is the correct diagnosis made and effective
      therapies initiated. Clues to an early diagnosis include thrombocytosis and
      sclerotic bone lesions on plain skeletal radiographs. Therapies that may be
      effective in patients with CIDP and MGUS-associated peripheral neuropathy
      (intravenous gammaglobulin and plasmapheresis) are not effective in patients with
      POEMS. Instead, the mainstays of therapy for patients with POEMS include
      irradiation, corticosteroids, and alkylator-based therapy, including high-dose
      chemotherapy with peripheral blood stem cell transplantation.

PMID- 16304405
TI  - Cryoglobulinemia.
AB  - Mixed cryoglobulinemia (MC) type II is a disorder characterized by circulating
      cold-precipitable immune complexes composed of polyclonal immunoglobulin IgG and
      monoclonal IgM rheumatoid factor (RF). The systemic vasculitis which
      characterizes the disease is caused by the deposition of immune complexes on the
      walls of small vessels, and by the subsequent activation of the complement
      cascade. MC may be asymptomatic or lead to clinical manifestations characterized
      by a typical triad--purpura, arthralgia, and weakness--and in some cases by a
      more serious vasculitis with neurologic and renal involvement. In the vast
      majority (more than 90%) of patients, MC is associated with hepatitis C virus
      (HCV) infection, which is considered the triggering factor of the disease. The
      association between cryoglobulinemia and HCV infection, and the possible
      evolution to B-cell lymphomas usually after long-term follow-up, suggest the role
      of HCV infection both in the pathogenesis of MC and in lymphomagenesis. In fact,
      the virus chronically stimulates the polyclonal proliferation of B cells from
      which a monoclonal population may emerge. This paper also reviews the treatment
      strategies for MC syndrome, emphasizing the issue of the eradication of HCV, and
      the clinical and biological activity of rituximab for selective B-cell control.

PMID- 16304406
TI  - Solitary bone and extramedullary plasmacytoma.
AB  - Less than 5% of patients with a plasma cell dyscrasia present with a single bone
      (SBP) or extramedullary plasmacytoma (EMP) without evidence of systemic disease
      (normocalcemia, absence of anemia, preservation of uninvolved immunoglobulins, or
      renal disease attributable to myeloma). Diagnosis requires biopsy confirmation of
      a monoclonal plasma cell infiltrate from a single site. The treatment of choice
      for both entities is radiotherapy given with curative intent (> 4000 cGy)
      resulting in long term disease-free survival in approximately 30% of patients
      with SBP and 65% of patients with EMP.

PMID- 16304407
TI  - Umbilical cord blood transplantation: a new alternative option.
AB  - Allogeneic hematopoietic stem cell transplantation is a life-saving procedure for
      hematopoietic malignancies, marrow failure syndromes, and hereditary
      immunodeficiency disorders. However, wide application of this procedure is
      limited by availability of suitably HLA-matched adult donors. Umbilical cord
      blood (UCB) has being increasingly used as an alternative hematopoietic stem cell
      source for these patients. To date, over 6000 UCB transplant procedures in
      children and adults have been performed worldwide using UCB donors. Broader use
      of UCB for adult patients is however limited by the available infused cell dose.
      This has prompted intensive research on ex vivo expansion of UCB stem cells and
      UCB graft-engineering including accessory cells able to improve UCB engraftment
      and reconstitution and for tissue regenerative potential. Recently, two large
      European and North American retrospective studies demonstrated that UCB is an
      acceptable alternative source of hematopoietic stem cells for adult recipients
      who lack HLA-matched adult donors. UCB is anticipated to address needs in both
      transplantation and regenerative medicine fields. It has advantages of easy
      procurement, no risk to donors, low risk of transmitting infections, immediate
      availability and immune tolerance allowing successful transplantation despite HLA
      disparity.

PMID- 16304408
TI  - Reduced-intensity conditioning regimens for hematologic malignancies: what have
      we learned over the last 10 years?
AB  - Reduced-intensity conditioning (RIC) regimens have been investigated for more
      than 10 years as an alternative to traditional myeloablative conditioning
      regimens. RIC regimens are being commonly used in older patients as well as in
      disorders in which traditional myeloablative conditioning regimens are associated
      with high rates of non-relapse mortality. Hodgkin disease, myeloma, and low-grade
      lymphoid malignancies have been the diseases most impacted by RIC regimens. RIC
      regimens have also been shown to be safe and effective in older patients as well
      as patients with co-morbidities, although patients with chemorefractory disease
      still have high relapse rates and poor outcomes. Patients with chemosensitive
      disease have outcomes similar to those obtained with conventional ablative
      therapies, and thus comparative trials are warranted. RIC regimens are associated
      with lower rates of severe toxicity and non-relapse mortality; however,
      infections, graft-versus-host disease, and relapse of primary disease remain the
      most common obstacles to a successful outcome. The impact on survival and the
      relative benefits of RIC allografting compared with traditional conditioning
      regimens or alternative therapy remain to be defined. Incorporating targeted
      therapies as part of the conditioning regimens or as maintenance therapies is
      currently being explored to reduce relapse rates without increasing toxicity.

PMID- 16304409
TI  - Haploidentical stem cell transplantation: the always present but overlooked
      donor.
AB  - Haploidentical stem cell transplantation is a treatment option for the
      approximately 70% of patients who do not have an HLA-identical sibling donor. The
      availability of a haploidentical donor in most families is a potential advantage,
      both for avoiding the need to find an alternative unrelated donor, and for the
      potentially more potent graft-versus-tumor effect that can be induced. The early
      complications of severe graft-versus-host disease (GVHD) following T-cell replete
      stem cell transplantation (SCT), and graft failure and recurrent malignancy
      (after T-cell depleted SCT) have limited the applications of this approach. Newer
      strategies employing T-cell depletion of the graft, using either very high-dose
      peripheral blood stem cells and/or more intensive conditioning therapy have
      overcome some of the problems of conventional transplantation. Nonmyeloablative
      SCT approaches have overcome some of the morbidity and mortality associated with
      the early complications of SCT and have been associated with favorable
      engraftment and GVHD profiles. Induction of mixed lymphohematopoietic chimerism
      as a platform for adoptive cellular immunotherapy (via delayed donor lymphocyte
      infusions) may have important application in avoiding early GVHD, while
      ultimately capturing a very potent graft-versus-tumor effect. Current strategies
      are focusing on improvement of immune reconstitution and prevention of recurrence
      of the underlying malignancy.

PMID- 16304410
TI  - Inherited platelet disorders.
AB  - The inherited platelet disorders are a heterogeneous collection of rare diseases
      that are infrequently encountered in clinical practice. They are, however,
      fascinating abnormalities, which have taught us a great deal about normal
      platelet biochemistry and physiology. In this section of the presentation we will
      review disorders of the platelet membrane, platelet granule packaging disorders,
      the hereditary macrothrombocytopenias, platelet signaling disorders and disorders
      of platelet coagulant function. The molecular basis of the disorders, the
      cardinal features of their clinical presentation and best methods to make their
      diagnosis and the latest information regarding therapy will be presented.

PMID- 16304411
TI  - Acquired disorders of platelet function.
AB  - A qualitative abnormality of platelet function should be considered in patients
      with mucocutaneous bleeding in the absence of thrombocytopenia or von Willebrand
      disease. Antiplatelet drugs are the most common cause of acquired platelet
      disorders leading to bleeding. Uremia, hepatic cirrhosis, myeloma and related
      disorders, polycythemia vera, essential thrombocythemia, and cardiopulmonary
      bypass have long been recognized as clinical situations in which platelet
      dysfunction may contribute to bleeding. When an acquired platelet disorder is
      suspected, it is useful to examine platelet function by measuring the bleeding
      time, examining platelet-dependent closure time in a platelet function analyzer
      and performing platelet aggregometry. When a specific acquired platelet disorder
      is diagnosed, many treatment options are available including controlling the
      underlying disease, giving platelet transfusions and administering a hemostatic
      drug.

PMID- 16304412
TI  - Platelets and thrombosis in myeloproliferative diseases.
AB  - The myeloproliferative disorders have been the "poor cousins" in the family of
      hematological malignancies for some time. Recently this field has advanced
      considerably with the description of a mutation in the JAK2 kinase detectable in
      the majority of patients and the publication of two landmark clinical trials-
      ECLAP and MRC PT1. But although both ECLAP and MRC PT1 inform clinical management
      and allude to the complexities of thrombosis we still lack fundamental knowledge,
      and our understanding of thrombosis in these conditions has not paralleled
      advances in the field of thrombosis and vascular biology. The predominant
      clinical complications of essential thrombocythemia and polycythemia vera are
      thrombotic and hemorrhagic; these significantly impact upon prognosis and quality
      of life. Here the current status of our knowledge is reviewed with specific
      emphasis upon the role of the platelet in the pathogenesis of thrombosis as well
      as the impact of recent data from ECLAP and MRC PT1.

PMID- 16304413
TI  - Management of bleeding disorders in children.
AB  - Diagnosis and management of congenital and acquired bleeding disorders in
      children requires not only an understanding of the unique characteristics of
      pediatric hemostasis but also the natural course of bleeding disorders in
      children, which may differ substantially from the course observed in adult
      patients. In this article, three bleeding disorders of great importance to the
      pediatric hematologist are reviewed: neonatal alloimmune thrombocytopenia (NAIT),
      hemophilia and immune-mediated thrombocytopenic purpura (ITP). Current aspects of
      management are outlined. The unique physiology of transplacental transfer of
      maternally derived anti-platelet antibodies can result in neonatal immune
      thrombocytopenia, a significant cause of morbidity and mortality from bleeding in
      affected infants. For patients with hemophilia, approaches to treatment have
      shifted over the past decade from on-demand therapy to prophylaxis, either
      primary of secondary, resulting in delay of onset or complete avoidance of
      hemophilic arthropathy. Hemophilic inhibitors often develop in young children,
      prompting the need for a thorough understanding of the use of bypassing agents as
      well as immune tolerance induction in the young child. Finally, although several
      management strategies for ITP of childhood have been shown to improve the
      platelet count, side effects associated with corticosteroids, IVIg, anti-D and
      splenectomy force the practitioner to also consider the option of carefully
      observing, but not treating, the child with ITP.

PMID- 16304414
TI  - Diagnosis and management of mild bleeding disorders.
AB  - Mild bleeding disorders are a common reason for a referral to a hematologist and
      these conditions can be challenging to evaluate. Recent research has highlighted
      that some bleeding symptoms are quite common in the general population and that
      there is clinical variability in symptom expression among individuals with
      defined bleeding problems. Moreover, bleeding risks for many bleeding disorders
      are unknown. This article reviews symptoms and problems that can be considered
      suspicious of a mild form of bleeding disorder and the diagnostic investigations
      useful to evaluate these problems. A stepwise approach is presented for the
      diagnostic evaluation, to allow detection of common and rare coagulation and
      fibrinolytic defects, and adequate assessments of potential von Willebrand factor
      and platelet problems. Some common problems in the diagnosis and management of
      mild bleeding problems are reviewed, including the common failure to establish a
      diagnosis with testing. An approach is proposed for translation of knowledge to
      patients who are challenged by mild bleeding problems.

PMID- 16304415
TI  - New perspectives in hemophilia treatment.
AB  - A variety of factor concentrates are currently available for replacement therapy
      for patients with hemophilia. These differ by several parameters, including
      source (pooled from pooled blood vs recombinant), purity, pathogen inactivation,
      and by the presence or absence of extraneous proteins such as albumin. The choice
      of replacement product reflects both safety issues of pathogen transmission or
      inhibitor development, and personal preferences of the patient and the physician.
      In general, currently available products are viral pathogen-free, although there
      is debate about the risk of transmission of parvovirus B19 and prion pathogens.
      Because of this very small risk, recombinant factor is the treatment of choice in
      previously untreated patients. In addition, a subset of concentrates contain
      factor that is activated during manufacture, yielding activated products that can
      be used in the treatment of patients with inhibitors. Such activated products,
      especially recombinant factor VIIa (rFVIIa), have also acquired several off-label
      indications in the management of bleeding in non-hemophiliac patients. The
      management of hemophilia patients with inhibitors is an ongoing challenge. Immune
      tolerance induction using a desensitization technique is successful in up to 90%
      of patients with alloantibodies against factor VIII, with greatest success seen
      in patients with low titer inhibitors who are treated soon after detection of an
      alloantibody and in whom treatment includes administration of immunosuppression
      along with repeated infusions of high titer concentrates. Such therapy is less
      successful in patients with factor IX alloantibodies. Non-hemophiliac patients
      with acquired inhibitors represent a unique patient population that requires
      special management. These patients have a mortality rate that approaches 25%
      because of the association of acquired inhibitors with severe bleeding
      complications, occurrence in a largely elderly population, and the frequent
      presence of an underlying, often serious, primary medical condition. Treatment
      consists of immunosuppression with steroids, chemotherapy, or intravenous
      immunoglobulin. Recent studies using rituximab for selective B-cell depletion in
      these patients have been very promising, although prospective controlled studies
      have not yet been performed. Finally, although hemophilia A and B appear to be
      ideal diseases to target with gene therapy approaches, the promise of this
      therapy remains to be realized.

PMID- 16304416
TI  - Pathogenesis of atherosclerosis.
AB  - Atherosclerosis is no longer considered a disorder due to abnormalities in lipid
      metabolism. In fact, the inciting event of atherosclerosis is likely an
      inflammatory insult that occurs decades before the disease becomes clinically
      apparent. Rapidly evolving knowledge of the pathogenesis of atherosclerosis,
      coupled with novel, target-specific therapies, is revolutionizing the treatment
      of atherosclerosis. As a result, a variety of treatments are now undergoing
      evaluation for their ability to ameliorate the inflammatory pathways likely to
      cause the atherosclerotic process to initiate and propagate. Once initiated,
      atherosclerosis progresses as a result of a well-studied series of changes in the
      constituent cellular make-up of the vessel wall. Specific cytokine-mediated
      events in this cycle are required for lesional growth. The clinical
      manifestations of atherosclerosis occur so late in this process that
      interventions such as percutaneous coronary interventions can deal with isolated
      areas of disease; however, they do not influence the underlying disease process.

PMID- 16304417
TI  - Genetic risk factors for arterial thrombosis and inflammation.
AB  - Arterial thrombosis is a central pathologic mechanism contributing to myocardial
      infarction and stroke, together the leading causes of death in developed
      countries. This article reviews the current state of knowledge concerning the
      role of inherited variation in hemostatic and inflammatory factor genes in
      determining the risk of arterial thrombosis/ischemic heart disease. Despite
      considerable progress in identifying important genetic risk factors underlying
      predisposition to venous thrombosis, the genetic factors contributing to the risk
      for arterial thrombosis remain largely unknown. However, the rapid development of
      powerful new genomic resources should facilitate considerably more sophisticated
      analyses, leading to novel insight into the molecular pathophysiology of this
      important set of human diseases.

PMID- 16304418
TI  - The cardiovascular pharmacology of COX-2 inhibition.
AB  - Selective inhibitors of cyclooxygenase (COX)-2, the coxibs, were developed to
      inhibit inflammatory prostaglandins derived from COX-2, while sparing
      gastroprotective prostaglandins primarily formed by COX-1. However, COX-2-derived
      prostaglandins mediate not only pain and inflammation but also affect vascular
      function, the regulation of hemostasis/ thrombosis, and blood pressure control.
      All coxibs depress COX-2-dependent prostacyclin (PGI(2)) biosynthesis without
      effective suppression of platelet COX-1-derived thromboxane (Tx) A(2), unlike
      aspirin or traditional nonsteroidal anti-inflammatory drugs, which inhibit both
      COX-1 and COX-2. The actions of PGI(2) oppose mediators, which stimulate
      platelets, elevate blood pressure, and accelerate atherogenesis, including
      TxA(2). Indeed, structurally distinct inhibitors of COX-2 have increased the
      likelihood of hypertension, myocardial infarction and stroke in controlled
      clinical trials. The detection of these events in patients is related to the
      duration of exposure and to their baseline risk of cardiovascular disease. Thus,
      coxibs should be withheld from patients with preexisting cardiovascular risk
      factors, and exposed patients at low cardiovascular baseline risk should be
      monitored for changes in their risk factor profile, such as increases in arterial
      blood pressure.

PMID- 16304419
TI  - Inherited risk factors for venous thrombosis.
AB  - Venous thrombosis occurs as a consequence of genetic and environmental risk
      factors. Since the discovery of factor V Leiden, the most common genetic risk
      factor, there has been intense interest in clarifying the roles of genes and the
      environment with thrombosis risk. The translation of this risk information to
      clinical practice is a challenging one in the setting of a rapidly expanding
      knowledge base that includes application of genetic medicine. There are benefits,
      but also potential harms, of testing for inherited disorders associated with
      thrombosis. This paper reviews inherited risk factors for thrombosis and discuss
      clinical applications of testing.

PMID- 16304420
TI  - Acquired risk factors for venous thromboembolism in medical patients.
AB  - Acute venous thromboembolism (VTE) is a serious and potentially fatal disorder,
      which often complicates the course of hospitalized patients, but may also affect
      ambulatory and otherwise healthy people. While the introduction of
      thromboprophylactic measures is expected to have reduced the occurrence of
      postoperative VTE, there is an increasing awareness of the importance of medical
      conditions in determining thromboembolic events. Among the conditions that
      predispose patients to VTE are increasing age, cancer and its treatment,
      prolonged immobility, stroke or paralysis, previous VTE, congestive heart
      failure, acute infection, pregnancy or puerperium, dehydration, hormonal
      treatment, varicose veins, long air travel, acute inflammatory bowel disease,
      rheumatologic disease, and nephrotic syndrome. Other factors that have recently
      been associated with an increased risk of VTE disorders include persistent
      elevation of D-dimer and atherosclerotic disease. Recognition of the incidence
      and clinical importance of thrombosis will most likely encourage more widespread
      use of antithrombotic prophylaxis in medical patients.

PMID- 16304421
TI  - Thrombosis and the antiphospholipid syndrome.
AB  - The antiphospholipid syndrome is an antibody-mediated hypercoagulable state
      characterized by recurrent venous and arterial thromboembolic events. Several
      studies have determined that the frequency of antiphospholipid syndrome in
      patients presenting with a venous thromboembolic event is between 4% and 14%.
      Because of the high risk for recurrent thromboembolism in these patients, current
      recommendations suggest a longer, potentially lifelong, course of antithrombotic
      therapy following an initial event. Although most authorities agree on an
      extended course of therapy, considerable controversy surrounds the optimal target
      therapeutic INR for patients with antiphospholipid syndrome. For an initial
      venous thromboembolic event, a target INR of 2.0 to 3.0 is supported by two
      prospective, randomized clinical trials. In contrast, relatively limited data
      exist for an initial arterial thromboembolic event in patients who have the
      antiphospholipid syndrome, and therapeutic recommendations range from aspirin to
      warfarin with a high target INR. Recurrent thromboembolic events can be extremely
      difficult to treat, and some patients may benefit from the addition of
      immunosuppressive therapies. Importantly, as many as 50% of the initial
      thromboembolic events sustained by patients with antiphospholipid antibodies
      occur in the setting of additional, coincident prothrombotic risk factors,
      indicating the importance of addressing any additional risk factors, such as
      hypercholesterolemia, in these patients. Prospective studies are needed to
      address the role of thromboprophylactic strategies in asymptomatic individuals
      with antiphospholipid antibodies in the absence of additional risk factors.

PMID- 16304422
TI  - Evaluation of hematopoietic stem cell donors.
AB  - Donation of hematopoietic stem cells, either through bone marrow or peripheral
      blood collection, is a generally safe procedure for healthy donors. Serious
      adverse events are uncommon and death is exceedingly rare. Nevertheless, all
      donors must be carefully evaluated and fully informed prior to donation. This
      should be done by clinicians having good understanding of the potential physical
      and psychological complications of donation and the factors that may increase
      these risks. Additionally, donors and graft products must be evaluated for the
      potential to transmit infections and other diseases to the recipient and to
      satisfy an increasing number of national and international regulatory
      requirements. Donors must be able to provide informed consent without coercion or
      pressure. Special attention to the clinical, psychological and social needs of
      pediatric donors is necessary.

PMID- 16304423
TI  - Technology for enhanced transfusion safety.
AB  - Data from reporting systems around the world document that non-infectious hazards
      are the leading cause of serious morbidity or mortality resulting from blood
      transfusion. Among these non-infectious hazards, mis-transfusion represents the
      most frequently observed serious hazard and occurs at an estimated rate of 1 in
      14,000 transfusions. Mis-transfusion events result from "lapse errors" (slip ups)
      rather than cognitive mistakes. Lapse errors are more likely to occur during
      repetitive tasks when individuals are distracted, rushed, or fatigued--conditions
      to which machines are not susceptible. The final bedside check and the collection
      of patient samples for pre-transfusion testing are key "error spots" and are
      candidates for new technology innovation. Existing technology includes non
      computerized devices; bedside devices based on bar code technology; and the use
      of radiofrequency chips. Several commercial systems employing bar-code technology
      have reached clinical application or are undergoing refinement. Radiofrequency
      based systems are on the near horizon. Nearly all systems begin with the
      application of machine-readable data to the patient's wristband. The third error
      spot--the decision to transfuse--will be a challenging area for future
      application of information technology. Computerized physician order-entry,
      decision support and ultimately active computer-based decision-making are
      expected to enhance transfusion decisions. Despite the explosive growth in
      information technology in modern society, healthcare has lagged behind many other
      sectors in the use of enhanced information technology. Studies are needed to
      identify which technologies improve patient outcomes. Healthcare workers,
      administrators, and regulators need to embrace the use of new technology in order
      to reduce errors and improve safety for patients.

PMID- 16304424
TI  - The transfusion services committee--responsibilities and response to adverse
      transfusion events.
AB  - Healthcare institutions in the United States must review blood transfusion
      practices and adverse outcomes in order to receive payments from the Centers for
      Medicare/Medicaid program, but it is not required for a specific committee to be
      assigned to oversee the review process. Regardless of the group or individuals
      responsible, the review process must include a program of quality assessment and
      performance improvement that is ongoing, hospital-wide, and data-driven, reflects
      the complexity of the hospital's organization and services, and involves all
      hospital departments and services (including those contracted). To be most
      effective, the performance improvement activity should be prioritized around high
      risk, high-volume activities and/or in problem-prone areas. Even if a hospital
      elects not to receive payments from Medicare, it must still comply with
      applicable sections of the Code of Federal Regulations pertaining to transfusion
      services such as the follow up of adverse outcomes of transfusion.

PMID- 16304425
TI  - Integrative medicine in hematology/oncology: benefits, ethical considerations,
      and controversies.
AB  - Integrative Medicine (IM), a newly emerging field, has evolved from Complementary
      and Alternative Medicine (CAM). CAM refers to diverse medical and health care
      systems, practices, and products that are not presently considered part of
      conventional medicine and generally have limited scientific evidence. In the US,
      CAM is a multi-billion dollar, unregulated industry with potential benefits and
      risks to consumers, including cancer patients, who are high utilizers of
      complementary therapies. Patients' CAM use often is unsupervised by physicians,
      yet patients need the advice and guidance of their hematologists/oncologists as
      part of total cancer care. Ethical and legal issues physicians need to address
      include inquiring about and educating patients regarding potential interactions
      (e.g., drug-herb, radiation-antioxidant) or product contaminants, while
      discussing other therapies that may alleviate symptoms and/or improve quality of
      life. Administratively, CAM offerings in medical settings require relevant
      policies and procedures, such as properly credentialing practitioners and
      providing financial assistance counseling for those who cannot afford fee-for
      service. Unlike "Alternative Medicine," the goal of IM is to combine mainstream
      medical therapies and CAM therapies (e.g., acupuncture, meditation, music
      therapy) that have some high-quality scientific evidence of safety and
      effectiveness. The Society for Integrative Oncology (SIO), a new international
      organization of oncology professionals studying and integrating effective
      complementary therapies in cancer care, serves as a forum for presenting
      scientific data on these therapies while emphasizing the importance of developing
      infrastructure that promotes IM principles and practices. The ultimate goal is to
      develop multidisciplinary expertise and therapeutic synergy between conventional
      and complementary therapies.

PMID- 16304426
TI  - Practical and ethical issues with genetic screening.
AB  - Clinical hematologists are faced with a growing list of new genetic-based tools
      for identifying a patient's risk of disease. While many of the disease-specific
      tests are readily available, validation studies are required. Furthermore,
      genetic-based tests are being pushed to their technical limits, such as testing a
      single cell prior to embryo selection and transfer for couples at risk of genetic
      disease. As a result, misdiagnosis or misinterpretation of the data may result.
      As new genetic testing opportunities proliferate, the hematologist needs to be
      aware of the medical and legal issues surrounding their use. Furthermore, the
      hematologist needs to consider the psychological, ethical and social implications
      of this new field of genomic-based medicine.

PMID- 16304427
TI  - Medical errors.
AB  - Following the 2000 report of the Institute of Medicine, To Err Is Human, which
      documented that as many as 98,000 people in this country die of medical errors
      every year, medical, hospital, and governmental agencies began to consider
      changes in hospital systems. The report had found that errors were much more
      likely to result from systemic problems than from inept health care providers.
      Progress in reinventing hospital systems has been very slow, although some
      institutions have made great gains."Medical errors" may be of several types. Some
      lead to malpractice claims, many do not. Many people who have been severely
      injured by errors never file claims. Making a medical mistake is not necessarily
      "malpractice." There are six elements a patient must prove in order to win a
      malpractice case: a physician-patient relationship must exist, the care provider
      must owe the patient a duty of care, evidence (usually expert testimony) must be
      presented that there was a failure in some part of the duty of care, there must
      proof that the lack of care was the proximate cause of harm, and proof of
      evidence that harm occurred. The patient must also prove his or her assessment of
      damages. Solutions to the problem of patient injuries are suggested.

PMID- 16304428
TI  - Cancer survivorship--pediatric issues.
AB  - The last three decades have seen tremendous improvements in survival of children
      diagnosed with cancer, with the 5-year survival rate approaching 80%. This
      improvement in survival has resulted in a growing population of childhood cancer
      survivors. Use of cancer therapy at an early age can produce complications that
      may not become apparent until years later. Approximately two thirds of the
      survivors of childhood cancer will experience at least one late effect, and about
      one third will experience a late effect that is severe or life threatening. Long
      term complications in childhood cancer survivors, such as impairment in growth
      and development, neurocognitive dysfunction, cardiopulmonary compromise,
      endocrine dysfunction, renal impairment, gastrointestinal dysfunction,
      musculoskeletal sequelae, and subsequent malignancies, are related not only to
      the specific therapy employed, but may also be determined by individual host
      characteristics. We review the known late effects of treatment in survivors of
      childhood cancer in order to suggest reasonable starting points for evaluation of
      specific long-term problems in this unique but growing population. The Children's
      Oncology Group (COG) has developed risk-based, exposure-related guidelines for
      follow-up care that are available at www.surivorshipguidelines.org.

PMID- 16304429
TI  - Considerations for adult cancer survivors.
AB  - With improvements in outcome, increased numbers of adult cancer patients survive
      free of their primary malignancy. Today, about 60% of adult patients diagnosed
      with cancer will survive 5 years after diagnosis. Therefore, immediate survival
      is no longer the sole concern. The aim of the cancer treatment now is to cure a
      patient's underlying disease and, at the same time, to minimize the incidence of
      post-treatment complications and ensure the best possible long term quality of
      life. The long time span between initial therapy and late effects, the multiple
      factors influencing cancer-related health risk and the unknown effect of
      treatment on normal aging are common characteristics of late effects. While the
      treatment strategy for a cancer patient depends widely on the type and extension
      of the disease, considerations for a long-term survivor depend much more on the
      type of treatment applied, age of the patient, and the patient's general health
      status as well as his or her familial and social integration. We discuss, based
      on the most recent knowledge, some typical examples of late effects in cancer
      survivors and the practical recommendations that could assist practitioner and
      patient decision about appropriate healthcare for specific clinical
      circumstances.

PMID- 16304430
TI  - Sexuality and fertility after cancer.
AB  - As more people achieve long-term survival after cancer, sexual dysfunction and
      infertility have increasingly been recognized as negative consequences that
      impact quality of life. Sexual dysfunction is a frequent long-term side effect of
      cancer treatment, but damage to different underlying physiological systems is
      salient in men versus women. Men frequently have erectile dysfunction (ED)
      related to damage to the autonomic nervous system and/or reduced circulation of
      blood to the penis. Hormonal impairment of sexual function is less common. Women,
      in contrast, are able to overcome damage to autonomic nerves if genital tissues
      remain structurally intact and estrogenized. Female sexual dysfunction is
      frequently associated with sudden premature ovarian failure or direct effects of
      radiation fibrosis or scar tissue causing pain with sexual activity. The lack of
      validated interventions for sexual rehabilitation after cancer is a major
      problem, as is finding cost-effective ways of providing services. Concerns about
      fertility are also a major source of distress to people treated for cancer during
      childhood or young adulthood, yet many young survivors do not recall any
      discussion about future childbearing potential with their oncology team. Since
      fertility preservation is becoming more practical for both men and women,
      producing patient and professional educational materials and developing
      professional practice guidelines should be high priorities for oncology
      societies.

PMID- 16304432
TI  - On the molecular origins of the chronic myeloproliferative disorders: it all
      makes sense.

PMID- 16304431
TI  - Anemia in the elderly: a public health crisis in hematology.
AB  - Over 3 million people in the United States aged 65 years and older are anemic.
      This condition is associated with significant functional impairment and, perhaps,
      increased mortality. In March 2004, the American Society of Hematology (in
      conjunction with the National Institute of Aging) convened a "blue ribbon" panel
      of twenty physicians who are experts on various aspects of this topic. This paper
      highlights important consensus concepts resulting from that meeting. In
      particular, four areas of thought are shared. First, the epidemiology of anemia
      in the elderly is reviewed, including its definition, its expression in different
      racial groups, and its wide-ranging manifestations. Second, the pathophysiology
      of anemia in the elderly is reviewed as pertains to three general etiological
      categories (nutritional, chronic diseases, and so-called "unexplained" anemias).
      Particular emphasis is given to pathophysiologic mechanisms of anemia that are
      potentially unique to this age group. Third, a practical approach to the
      diagnosis and management of anemia for this patient population for the practicing
      hematologist is provided. Finally, the public health implications of anemia in
      the elderly for key stakeholder constituencies will be discussed in the oral
      presentation.

PMID- 16304433
TI  - Hematology grants K08 and K23.
AB  - The first National Institutes of Health (NIH) grant awarded to physician
      scientists is often a K08 or K23 award. This chapter is designed for the
      Hematology Fellow who is preparing for an independent faculty position in 3-5
      years. The topics covered include deciding which award to apply for, advice about
      planning and writing the application, as well as a description of the review
      process and how candidates can make their application stand out.

PMID- 16304435
TI  - Smokeless tobacco and periodontal disease.

PMID- 16304436
TI  - Diffusion coefficient of fluoride in dental plaque.

PMID- 16304437
TI  - Discovering the impact of Ronald Gibbons on dental research and beyond.

PMID- 16304438
TI  - Biological approaches to bone regeneration by gene therapy.
AB  - Safe, effective approaches for bone regeneration are needed to reverse bone loss
      caused by trauma, disease, and tumor resection. Unfortunately, the science of
      bone regeneration is still in its infancy, with all current or emerging therapies
      having serious limitations. Unlike current regenerative therapies that use single
      regenerative factors, the natural processes of bone formation and repair require
      the coordinated expression of many molecules, including growth factors, bone
      morphogenetic proteins, and specific transcription factors. As will be developed
      in this article, future advances in bone regeneration will likely incorporate
      therapies that mimic critical aspects of these natural biological processes,
      using the tools of gene therapy and tissue engineering. This review will
      summarize current knowledge related to normal bone development and fracture
      repair, and will describe how gene therapy, in combination with tissue
      engineering, may mimic critical aspects of these natural processes. Current gene
      therapy approaches for bone regeneration will then be summarized, including
      recent work where combinatorial gene therapy was used to express groups of
      molecules that synergistically interacted to stimulate bone regeneration. Last,
      proposed future directions for this field will be discussed, where regulated gene
      expression systems will be combined with cells seeded in precise three
      dimensional configurations on synthetic scaffolds to control both temporal and
      spatial distribution of regenerative factors. It is the premise of this article
      that such approaches will eventually allow us to achieve the ultimate goal of
      bone tissue engineering: to reconstruct entire bones with associated joints,
      ligaments, or sutures. Abbreviations used: BMP, bone morphogenetic protein; FGF,
      fibroblast growth factor; AER, apical ectodermal ridge; ZPA, zone of polarizing
      activity; PZ, progress zone; SHH, sonic hedgehog; OSX, osterix transcription
      factor; FGFR, fibroblast growth factor receptor; PMN, polymorphonuclear
      neutrophil; PDGF, platelet-derived growth factor; IGF, insulin-like growth
      factor; TGF-beta, tumor-derived growth factor beta; CAR, coxsackievirus and
      adenovirus receptor; MLV, murine leukemia virus; HIV, human immunodeficiency
      virus; AAV, adeno-associated virus; CAT, computer-aided tomography; CMV,
      cytomegalovirus; GAM, gene-activated matrix; MSC, marrow stromal cell; MDSC,
      muscle-derived stem cell; VEGF, vascular endothelial growth factor.

PMID- 16304439
TI  - Immunomodulation with enterotoxins for the generation of secretory immunity or
      tolerance: applications for oral infections.
AB  - The heat-labile enterotoxins, such as cholera toxin (CT), and the labile toxins
      types I and II (LT-I and LT-II) of Escherichia coli have been extensively studied
      for their immunomodulatory properties, which result in the enhancement of immune
      responses. Despite superficial similarity in structure, in which a toxic A
      subunit is coupled to a pentameric binding B subunit, different toxins have
      different immunological properties. Administration of appropriate antigens
      admixed with or coupled to these toxins by oral, intranasal, or other routes in
      experimental animals induces mucosal IgA and circulating IgG antibodies that have
      protective potential against a variety of enteric, respiratory, or genital
      infections. These include the generation of salivary antibodies that may protect
      against colonization with mutans streptococci and the development of dental
      caries. However, exploitation of these adjuvants for human use requires an
      understanding of their mode of action and the separation of their desirable
      immunomodulatory properties from their toxicity. Recent findings have revealed
      that adjuvant action is not critically dependent upon the enzymic activity of the
      A subunits, and that the isolated B subunits may exert different effects on cells
      of the immune system than do the intact toxins. Interaction of the toxins with
      immunocompetent cells is not exclusively dependent upon their conventional
      ganglioside receptors. Immunomodulatory effects have been observed on dendritic
      cells, macrophages, CD4(+) and CD8(+) T-cells, and B-cells. Numerous factors
      including the precise form of the toxin adjuvant, properties of the antigen,
      whether and how they are coupled, route of administration, and species of animal
      model-affect the outcome, whether this is enhanced humoral and cellular immunity,
      or specific induced tolerance toward the antigen.

PMID- 16304440
TI  - Genes and related proteins involved in amelogenesis imperfecta.
AB  - Dental enamel formation is a remarkable example of a biomineralization process.
      The exact mechanisms involved in this process remain partly obscure. Some of the
      genes encoding specific enamel proteins have been indicated as candidate genes
      for amelogenesis imperfecta. Mutational analyses within studied families have
      supported this hypothesis. Mutations in the amelogenin gene (AMELX) cause X
      linked amelogenesis imperfecta, while mutations in the enamelin gene (ENAM) cause
      autosomal-inherited forms of amelogenesis imperfecta. Recent reports involve
      kallikrein-4 (KLK4), MMP-20, and DLX3 genes in the etiologies of some cases. This
      paper focuses mainly on the candidate genes involved in amelogenesis imperfecta
      and the proteins derived from them, and reviews current knowledge on their
      structure, localization within the tissue, and correlation with the various types
      of this disorder.

PMID- 16304441
TI  - Amelotin--a Novel Secreted, Ameloblast-specific Protein.
AB  - We aimed to analyze the differential gene expression in various murine dental
      tissues, expecting to find novel factors that are involved in tooth formation. We
      here describe the identification of a novel ameloblast-specific gene, amelotin
      (AMTN), by differential display polymerase chain-reaction (DD-PCR) analysis of
      microdissected ameloblasts, odontoblasts, dental pulp, and alveolar bone cells of
      10-day-old mouse incisors. The conceptually translated protein sequence was
      unique and showed significant homology only with its human orthologue. The
      amelotin genes from mouse and human displayed a similar exon-intron structure and
      were expressed from loci on chromosomes 5 and 4, respectively, which have been
      associated with various forms of amelogenesis imperfecta. Expression of amelotin
      mRNA was restricted to maturation-stage ameloblasts in developing murine molars
      and incisors. Amelotin protein was efficiently secreted from transfected cells in
      culture. Taken together, our findings suggest that amelotin is a novel factor
      produced by ameloblasts that plays a critical role in the formation of dental
      enamel.

PMID- 16304442
TI  - Low-fluoride dentifrice and gastrointestinal fluoride absorption after meals.
AB  - A low-fluoride (F) dentifrice has been recommended to reduce the risk of dental
      fluorosis, but its anti-caries efficacy is questionable compared with that of
      conventional dentrifices (1000-1100 microg F/g). The tested hypothesis was that
      conventional dentifrices might be safe if used soon after meals, since food
      interferes with F absorption. In a crossover, double-blind study, 11 volunteers
      ingested a dentifrice slurry containing 0 (placebo), 550 (low F), or 1100 microg
      F/g in 3 gastric content situations: on fasting, or 15 min after breakfast or
      lunch. F was analyzed in saliva and 24-hour urine samples. The conventional
      dentifrice ingested after lunch resulted in only 10% higher F absorption than the
      low-F ingested on fasting. Analysis of the data suggests that the risk of
      fluorosis could be reduced by the use of either a low-F dentifrice or a
      conventional dentifrice, if toothbrushing occurred soon after meals.

PMID- 16304443
TI  - Sealant and fluoride varnish in caries: a randomized trial.
AB  - Little is known about the effect of discontinuation of sealant or fluoride
      varnish. The purpose of this study was to compare sealant with fluoride varnish
      in the prevention of occlusal caries in permanent first molars of children over a
      nine-year period: 4 yrs for program evaluation plus 5 yrs of discontinuation. A
      clinical trial was conducted on three groups of six- to eight-year-old
      schoolchildren: a control group (n = 45); a group (n = 37) in which sealant was
      applied and reapplied up to 36 mos; and a group (n = 38) in which fluoride
      varnish was applied and re-applied up to 42 mos. Percent caries reduction was
      studied in these initially healthy molars with complete occlusal eruption: 129
      (control), 113 (sealant), and 129 (varnish) molars met inclusion criteria. Of
      these, 76.7%, 26.6%, and 55.8% had developed occlusal caries at 9 yrs, which
      implies caries reductions of 65.4% (SE = 8.5%) for sealants vs. control and 27.3%
      (SE = 10.2%) for varnish vs. control. Furthermore, the varnish program was not
      effective during the discontinuation period.

PMID- 16304444
TI  - Effectiveness of 4 pulpotomy techniques--randomized controlled trial.
AB  - Pulpotomy is the accepted therapy for the management of cariously exposed pulps
      in symptom-free primary molars; however, evidence is lacking about the most
      appropriate technique. The aim of this study was to compare the relative
      effectiveness of the Er:YAG laser, calcium hydroxide, and ferric sulfate
      techniques with that of dilute formocresol in retaining such molars symptom-free.
      Two hundred primary molars in 107 healthy children were included and randomly
      allocated to one of the techniques. The treated teeth were blindly re-evaluated
      after 6, 12, 18, and 24 months. Descriptive data analysis and logistic regression
      analysis, accounting for each patient's effect by a generalized estimating
      equation (GEE), were used. After 24 months, the following total and clinical
      success rates were determined (%): formocresol 85 (96), laser 78 (93), calcium
      hydroxide 53 (87), and ferric sulfate 86 (100). Only calcium hydroxide performed
      significantly worse than formocresol (p = 0.001, odds ratio = 5.6, 95% confidence
      interval 2.0-15.5). In conclusion, calcium hydroxide is less appropriate for
      pulpotomies than is formocresol.

PMID- 16304445
TI  - Functional gene polymorphisms in aggressive and chronic periodontitis.
AB  - There is strong evidence that genetic as well as environmental factors affect the
      development of periodontitis, and some suggestion that aggressive and chronic
      forms of the disease share the same genetic predisposition. This study addresses
      the hypothesis that there are both shared and unique genetic associations in
      these forms of periodontitis. A sample of 51 patients with aggressive disease, 57
      patients with chronic disease, and 100 healthy controls was recruited for this
      study. Ten functional polymorphisms in 7 candidate genes were genotyped. The
      results show statistically significant (p <or= 0.05) differences between genotype
      frequencies in aggressive and controls (IL-1B +3954 & IL-6 -174); chronic and
      controls (IL-6 -174 & VDR -1056); chronic and aggressive periodontitis (IL-1A 
      889); and periodontitis as a whole and controls (VDR -1056, TLR-4 399 & IL-6 
      174). These results suggest that there are in fact both shared and unique genetic
      associations in aggressive and chronic periodontitis.

PMID- 16304446
TI  - Does periodontal treatment improve glycemic control in diabetic patients? A meta
      analysis of intervention studies.
AB  - Previous analyses regarding effects of periodontal treatment on glycemic control
      included studies where causal association might not be assumed, or the results
      were reported non-quantitatively. We initiated this meta-analysis of 10
      intervention studies to quantify the effects of periodontal treatment on HbA1c
      level among diabetic patients, to explore possible causes for the discrepant
      reports, and to make recommendations for future studies. Data sources were
      MEDLINE (January, 1980, to January, 2005), the EBMR, Cochrane Register, and
      bibliographies of the published articles. Three investigators extracted data
      regarding intervention, outcomes, and effect size. A total of 456 patients was
      included in this analysis, with periodontal treatment as predictor and the actual
      change in hemoglobin A1c level as the outcome. The weighted average decrease in
      actual HbA1c level was 0.38% for all studies, 0.66% when restricted to type 2
      diabetic patients, and 0.71% if antibiotics were given to them. However, none was
      statistically significant.

PMID- 16304448
TI  - Streptococci dominate the diverse flora within buccal cells.
AB  - Previously, we reported that intracellular Actinobacillus actinomycetemcomitans,
      Porphyromonas gingivalis, and Tannerella forsythensis were present within buccal
      epithelial cells from human subjects, as lesser components of a polymicrobial
      flora. In this study, we further characterized that intracellular flora by using
      the same double-labeling techniques to identify Fusobacterium nucleatum,
      Prevotella intermedia, oral Campylobacter species, Eikenella corrodens, Treponema
      denticola, Gemella haemolysans, Granulicatella adiacens, and total streptococci
      within buccal epithelial cells. All those species were found within buccal cells.
      In every case, species recognized by green-labeled species-specific probes were
      accompanied by other bacteria recognized only by a red-labeled universal probe.
      Streptococci appeared to be a major component of the polymicrobial intracellular
      flora, being present at a level from one to two logs greater than the next most
      common species (G. adiacens). This is similar to what is observed in oral
      biofilms, where diverse species interact in complex communities that often are
      dominated by streptococci.

PMID- 16304447
TI  - Hydrolytic stability of self-etch adhesives bonded to dentin.
AB  - Functional monomers chemically interact with hydroxyapatite that remains within
      submicron hybrid layers produced by mild self-etch adhesives. The functional
      monomer 10-MDP interacts most intensively with hydroxyapatite, and its calcium
      salt appeared most hydrolytically stable, as compared with 4-MET and phenyl-P. We
      investigated the hypothesis that additional chemical interaction of self-etch
      adhesives improves bond stability. The micro-tensile bond strength (muTBS) of the
      10-MDP-based adhesive did not decrease significantly after 100,000 cycles, but
      did after 50,000 and 30,000 cycles, respectively, for the 4-MET-based and the
      phenyl-P-based adhesives. Likewise, the interfacial ultrastructure was unchanged
      after 100,000 thermocycles for the 10-MDP-based adhesive, while that of both the
      4-MET- and phenyl-P-based adhesives contained voids and less-defined collagen.
      The findings of this study support the concept that long-term durability of
      adhesive-dentin bonds depends on the chemical bonding potential of the functional
      monomer.

PMID- 16304449
TI  - Control of oral biofilm formation by an antimicrobial decapeptide.
AB  - Oral biofilms are mixed-species microbial communities, and their uncontrolled
      outgrowth can express as oral diseases. Antimicrobial peptides represent
      alternative classes of antimicrobials that exhibit selectivity for prokaryotes.
      We wanted to test the effect of a synthetic decapeptide antimicrobial, KSL, on
      the development of oral biofilms formed by isolated human salivary bacteria. We
      used differential interference contrast microscopy, coupled with a dual-flow cell
      system, to determine the effect of KSL on oral biofilm development. We used
      reductions of viable counts and confocal microscopy to assess the bactericidal
      activity of KSL on mature oral biofilms. KSL effectively blocked biofilm
      development. A significant effect on the viability of mature biofilms was
      observed when KSL was used in the presence of a surface-active agent, or after
      biofilms were mechanically disrupted. This study shows that KSL may be a useful
      adjunct for conventional oral hygiene to prevent plaque-mediated dental diseases.

PMID- 16304450
TI  - Role of TNF-alpha and its receptors in pericoronitis.
AB  - The classic stimulus for cellular cytokine production is bacterial
      lipopolysaccharide (endotoxin). It was therefore hypothesized that tumor necrosis
      factor-alpha (TNF-alpha) may be responsible for pericoronitis. TNF-alpha and its
      receptors were detected by immunohistochemical staining in third molar
      pericoronitis in ten patients and ten healthy control samples. The percentage of
      TNF-alpha positive cells was high in pericoronitis (p = 0.0317). TNF receptors
      TNF-R1 and TNF-R2 were found in macrophage- and fibroblast-like cells, vascular
      endothelial cells in post-capillary venules, and basal epithelial cells in
      pericoronitis, but were only weakly expressed in controls. Increased expression
      of interleukin-1beta and vascular cell adhesion molecule-1 was found as a
      biological indicator of TNF-alpha ligand-receptor interaction. Explanted tissues
      acquired destructive potential upon TNF-alpha stimulation, whereas TNF-alpha
      blockers controlled it in inflamed tissues. These findings suggest that, in
      pericoronitis, inflammatory and resident cells produce and respond to potent pro
      inflammatory cytokine TNF-alpha, with pathogenic and potential therapeutic
      relevance.

PMID- 16304451
TI  - Alpha 2 integrin +807 polymorphism in drug-induced gingival overgrowth.
AB  - Alpha2 integrin on fibroblasts is reported to play an important role in the
      induction of drug-induced gingival overgrowth, which is characterized by
      excessive accumulation of type I collagen in gingival connective tissue. Silent
      polymorphism 807 T/C within the alpha2 integrin gene is associated with high/low
      alpha2 integrin expression. The aim of this study was to test the hypothesis that
      expression of alpha2 integrin 807 T/C polymorphism correlates with drug-induced
      gingival overgrowth. A case-control study comparing 136 subjects taking calcium
      channel blockers (72 with vs. 64 without drug-induced gingival overgrowth)
      demonstrated that the frequency of the +807 C allele was significantly higher in
      the case group than in the controls (odds ratio, 3.61; 95% confidence interval,
      2.14 - 6.10; P < 0.05). The present findings suggest that the alpha2 +807 C
      allele is one of the genetic risk factors for drug-induced gingival overgrowth.

PMID- 16304452
TI  - Influence of androgens on gene expression in the BALB/c mouse submandibular
      gland.
AB  - Androgens have profound effects on the murine submandibular gland. Our objective
      was to determine the nature and extent of androgen control of gene expression in
      the submandibular gland, and to explore the degree to which this might account
      for known sex differences. Orchiectomized male BALB/c mice were treated with
      placebo- or testosterone-containing hormone pellets for 14 days. Glands were
      collected, and total RNA was isolated. Samples were analyzed for differentially
      expressed mRNAs by CodeLink microarrays, and the data were evaluated with
      GeneSifter. Androgens significantly (p < 0.05) influenced the expression of over
      1300 genes, and many (n = 366) of the genes differentially regulated by androgen
      treatment were also differentially expressed in males compared with the females
      in our previous study. These findings support our hypotheses that testosterone
      extensively influences gene expression in the male submandibular gland, and that
      many of the sex differences are due to androgens.

PMID- 16304453
TI  - Clock gene expression in the submandibular glands.
AB  - Clock genes, which mediate molecular circadian rhythms, are expressed in a
      circadian fashion in the suprachiasmatic nucleus and in various peripheral
      tissues. To establish a molecular basis for circadian regulation in the salivary
      glands, we examined expression profiles of clock-related genes and salivary gland
      characteristic genes. Clock-related genes-including Per1, Per2, Cry1, Bmal1,
      Dec1, Dec2, Dbp, and Reverbalpha-showed robust circadian expression rhythms in
      the submandibular glands in 12:12-hour light-dark conditions. In addition, a
      robust circadian rhythm was observed in amylase 1 mRNA levels, whereas the
      expression of other salivary-gland-characteristic genes examined was not
      rhythmic. The Clock mutation resulted in increased or decreased mRNA levels of
      Per2, Bmal1, Dec1, Dec2, and Dbp, and in Cry1-/- background, Cry2 disruption also
      increased or decreased mRNA levels of these clock-related genes and the amylase 1
      gene. These findings indicate that the Clock- and Cry-dependent molecular clock
      system is active in the salivary glands.

PMID- 16304454
TI  - HIV and hepatitis C virus coinfection: bad bedfellows.
AB  - Hepatitis C virus (HCV) infection is common in HIV-infected individuals and is
      responsible for increasing morbidity in these patients. HIV infection increases
      HCV replication and accelerates progression of HCV disease. HCV infection
      increases the risk of antiretroviral treatment. HCV genotype 1 is the predominant
      genotype in HCV/HIV-coinfected individuals living in the United States. State-of
      the-art treatment with peginterferon alfa plus ribavirin results in lower
      sustained HCV virologic response rates in patients with genotype 1 infection than
      in those infected with other genotypes. Data from studies of HCV infection
      treatment in coinfected patients are discussed, as are prospects for future
      therapy. This article summarizes a presentation on HIV/HCV coinfection by Robert
      T. Schooley, MD, at the International AIDS Society-USA course in San Francisco in
      June 2005.

PMID- 16304455
TI  - Selected primary-care issues in HIV disease.
AB  - Primary care for HIV-infected patients includes ensuring that eligible patients
      receive hepatitis B and A virus vaccinations, all women undergo appropriate
      screening and follow-up for cervical cytologic abnormalities, and all patients
      undergo routine screening for renal function abnormalities. Current guidelines in
      these specific areas of HIV primary care are reviewed. This article summarizes a
      presentation on issues in primary care for HIV-infected patients by David H.
      Spach, MD, at the 8th Annual Clinical Conference for Ryan white CARE Act
      clinicians in New Orleans in June 2005.

PMID- 16304456
TI  - Medicare part D and antiretroviral therapy: issues for HIV clinicians.
AB  - As of January 1, 2006, Medicare Plan D will add a drug benefit to Medicare,
      potentially affecting antiretroviral therapy for some 60,000 to 80,000
      beneficiaries with HIV infection or AIDS. Health care providers should know the
      basic details of Plan D and how it may affect coverage for Medicare beneficiaries
      with or without a previous drug benefit under Medicaid. Steps may need to be
      taken to ensure that there are no lapses in antiretroviral therapy during the
      transition from one pharmacy plan to another. This article summarizes a
      presentation on Medicare Plan D and antiretroviral therapy for patients with HIV
      or AIDS, given by Laura W. Cheever, MD, at the 8th Annual Clinical Conference for
      Ryan White CARE Act clinicians in New Orleans in June 2005, and developed by Dr
      Cheever and Mary R. Vienna, RN.

PMID- 16304457
TI  - Update of the drug resistance mutations in HIV-1: Fall 2005.
AB  - The International AIDS Society-USA (IAS-USA) Drug Resistance Mutations Group is
      marking 5 years as an independent volunteer panel of experts focused on
      identifying key HIV-1 drug resistance mutations. The goal of the effort is to
      quickly deliver accurate and unbiased information on these mutations to HIV
      clinical practitioners. The October/November 2005 version of the IAS-USA Drug
      Resistance Mutations Figures replaces the version published in this journal in
      March/April 2005. The IAS-USA Drug Resistance Mutations Figures are designed for
      use in identifying mutations associated with viral resistance to antiretroviral
      drugs and in making therapeutic decisions. Care should be taken when using this
      list of mutations for surveillance or epidemiologic studies of transmission of
      drug-resistant virus. A number of amino acid substitutions, particularly minor
      mutations, represent polymorphisms that in isolation may not reflect prior drug
      selective pressure or reduced drug susceptibility.

PMID- 16304458
TI  - Structure of Chlorobium vibrioforme 5-aminolaevulinic acid dehydratase complexed
      with a diacid inhibitor.
AB  - The structure of Chlorobium vibrioforme 5-aminolaevulinic acid dehydratase (ALAD)
      complexed with the irreversible inhibitor 4,7-dioxosebacic acid has been solved.
      The inhibitor binds by forming Schiff-base linkages with lysines 200 and 253 at
      the active site. The structure reported here provides a definition of the
      interactions made by both of the substrate molecules (A-side and P-side
      substrates) with the C. vibrioforme ALAD and is compared and contrasted with
      structures of the same inhibitor bound to Escherichia coli and yeast ALAD. The
      structure suggests why 4,7-dioxosebacic acid is a better inhibitor of the zinc
      dependent ALADs than of the zinc-independent ALADs.

PMID- 16304459
TI  - The reliability of immunoassay for determining the presence of opiates in the
      forensic setting.
AB  - Urine immunoassays are commonly used as a rapid screen for drugs of abuse in
      emergency room, hospital, clinic, and forensic settings. The authors were
      concerned whether or not a negative screen of the urine for opiates was of
      significance and indicative that analysis of blood for opiates was not necessary.
      Specifically, we wished to determine whether a negative test for opiates by
      immunoassay absolutely rules out an acute overdose, and if not, what percentage
      of cases with negative results have opiates in the blood. A retrospective
      analysis was performed using the toxicology results for cases ruled an acute
      narcotic overdose at the Bexar County Medical Examiner's Office between 1998 and
      2003. One hundred eighty-three cases met the criteria for the study. A false
      negative rate of approximately 15% was found using an immunoassay as compared
      with blood analysis for narcotics. The authors feel that while this rate may be
      acceptable in a clinical setting, it is unacceptable in a forensic setting.

PMID- 16304460
TI  - Gross and histologic postmortem changes of the skin.
AB  - Many methods have been attempted to accurately and systematically determine the
      estimated time of death in autopsy cases. Gross changes of the skin which occur
      during the postmortem interval have occasionally been used to estimate the time
      of death under different conditions; however, the postmortem gross and histologic
      changes of the skin have not been systematically analyzed. We sequentially
      studied the gross and microscopic appearance of skin in 3 individuals during the
      early postmortem interval (<1 week) in an outdoor, shaded, cool to temperate
      climate. Photos and skin biopsy specimens were taken from 4 sites (acral skin,
      scalp, dependent truncal skin, and nondependent truncal skin) every 12-24 hours
      on each individual. The gross appearance of the skin remarkably did not change
      significantly in any of the sites after 1 week of decomposition. Three main
      histologic changes were seen in the skin biopsy specimens: focal dermal-epidermal
      separation, eccrine duct necrosis, and dermal degeneration. Although bullae were
      not present in the gross examination of the skin, focal separation of the
      epidermis from the dermis was appreciated in several skin biopsies; however, the
      timing of development was unpredictable. Eccrine duct necrosis was another
      histologic finding and was relatively predictable, occurring in dependent and
      nondependent truncal skin biopsies from all 3 individuals between days 4 and 7.
      Dermal degeneration was a uniform histologic finding only in biopsies from
      nondependent truncal skin, occurring in all individuals on day 2. Although this
      study is limited by the small number of subjects and uncontrolled extrinsic
      factors, histologic findings, such as eccrine gland necrosis and dermal
      degeneration, in select cutaneous biopsies may be useful in estimating the time
      of death in the early postmortem interval.

PMID- 16304461
TI  - Suicide in children and adolescents: a 10-year retrospective review.
AB  - Suicide is second only to accidents as the most common cause of death for
      children and adolescents age 10 to 19 in Canada. All of the pediatric cases that
      were referred to the Hamilton Regional Forensic Pathology Unit from 1993 to 2002
      were reviewed. For the purpose of this study, pediatric deaths were defined as
      deaths in the age group of 1 day up to and including 19 years of age. Specific
      criteria for suicide were applied to each case, independent of the manner of
      death issued by the coroner. The criteria were 3-fold. First, homicide had to be
      ruled out by the police investigation and autopsy findings. Second, the method
      had to be consistent with self-infliction. Finally, there had to be some evidence
      of suicidal intent. Questionable cases were discussed among the authors, and if
      reasonable intent could not be established, then the case was excluded. The
      autopsy and police reports were examined in detail regarding age, sex, location
      and method of suicide, presence of suicide notes, and any contributing
      psychologic factors or stressors. Of the 501 pediatric autopsies performed during
      the 10-year period, 31 (6%) met the criteria of suicide. The majority of cases
      (87%) were in older adolescents (age 15 to 19), and the male to female ratio was
      2.4:1. Psychologic factors were identified in some of the cases, including
      depressed mood (77%), suicidal ideation (45%), previous suicide attempts (23%),
      and drug or alcohol problems (19%). Most of the suicides (61%) occurred in the
      victim's home, and 12 (39%) cases left a suicide note. In 9 cases (29%), alcohol
      or street drugs were detected postmortem, though in 8 cases toxicology was not
      performed. Hanging (48%) was the most common method of suicide, followed by
      firearms (13%), poisoning (10%), drowning (10%), and blunt force vehicular trauma
      (10%). Almost 60% of the male suicides were by hanging. No specific trend was
      identified in the 9 female suicides. These results were compared with similar
      studies within Canada and other countries. Overall, the method of suicide is
      dictated by what is convenient and readily available, though the acceptance of
      various suicide methods can change over time. Suicide prevention efforts should
      be tailored to address local trends.

PMID- 16304462
TI  - Pediatric drowning: a 20-year review of autopsied cases: I. Demographic features.
AB  - Drowning is a significant cause of childhood mortality in the developed world.
      Males and preschool-aged children are overrepresented in most series of pediatric
      drowning. To obtain a better understanding of age- and gender-related factors, a
      retrospective review of autopsy records over a 20-year period (1984-2003) for
      cases of drowning (exclusive of bathtub drownings) was performed. Sixty-three
      consecutive cases of drowning were identified in 45 males and 18 females (ratio
      2.5; P = 0.0007). The ages ranged from 9 months to 17 years, and most cases
      occurred in the 0- to 4-year age group (57%). Boys tended to be older than girls
      (5 years 9 months versus 4 years 4 months; P = 0.2133). Sites of drowning were
      open water (48%) and pools (44%), with children drowning in open water being
      significantly older than those drowning in pools (6 years 6 months versus 4 years
      6 months; P = 0.0462). Most boys drowned in open water (53%), whereas most girls
      drowned in pools (50%). Resuscitation was attempted after the drowning episode in
      84% of cases, with children aged 4 years or less having significantly higher
      rates than older children (P = 0.0346). The present study highlights differences
      in the pattern of drowning according to age and sex and may aid in developing
      targeted educational and preventative campaigns.

PMID- 16304463
TI  - Women who kill their children.
AB  - The killing of a newborn on the day of its birth is known as neonaticide. A child
      aged 1 through 16 has a different role in the family, and their murder is
      perceived differently. We would expect mothers charged with filicide to be drawn
      from a slightly different population than other child-killing mothers. METHOD:
      Our study was carried out at the Institute of Forensic Medicine in Angers over a
      10-year period. All the victims were autopsied at the Institute of Forensic
      Medicine in Angers. Information concerning the mothers was collected from
      forensic medical files, police reports, and legal files. Interviews and forensic
      psychiatric examinations were available for consultation. RESULTS: Our study
      concerns 17 observations of child-killing mothers and 19 child autopsies. In 2
      cases, the issue was in fact a double murder, with the mother killing all the
      siblings. The mean age was 3.5 years for victims and 29.5 years for the women.
      The majority of the mothers were married or lived with their partners. They often
      had an occupation. Generally the economic status was average. Head trauma,
      strangulation, suffocation, and drowning were the most frequent means of
      filicide. However, some mothers used more active methods such as striking and
      shooting. Disturbed or disturbing behavior was documented in 15 perpetrators.
      Seven women tried to commit suicide. It was often possible to identify apparent
      motivation for the offense. DISCUSSION: In our study, we can distinguish 2 types
      of killer mothers. We distinguished a first group made up of 5 mothers. These 5
      women killed their children in a general context of abused children and present
      similarities with the neonaticide mothers (young, immature). The other group of
      filicide mothers is different. They are generally older, married, and employed.
      The crime is usually premeditated, committed with the direct use of hands and
      sometimes very violent. To understand the motives or the source of the impulse to
      kill, we can use a classification such as Resnick's classification: mothers from
      the first group fall within the framework of accidental filicides: the risk and
      prevention factors are those of infanticide and ill treatment. For the other
      mothers, we can distinguish altruistic filicides (8 cases) and spouse revenge
      filicides (2 cases). Few of the mothers suffered from real psychiatric problems;
      however, most of them presented troubles which could have been taken into
      account. A lot of women showed signs of suicidal tendencies prior to the event,
      displaying aggressive and angry behavior. In general, suicide attempts tend to
      prevail. These offenders act out of an acute sensitivity to social regulation. A
      variety of psychosocial stresses appears to have been a major factor. These
      stresses include lack of social or marital support, economic difficulties, family
      stress, and unrealistic expectations of motherhood. The precipitating stress may
      have been a dispute. Prevention begins with the identification of potential
      perpetrators. Therefore, medical doctors have a significant role in relation to
      the prevention of child murder.

PMID- 16304464
TI  - Asphyxia by tracheobronchial thrombus.
AB  - Asphyxia secondary to airway obstruction has numerous underlying causes, both
      acute and chronic. Causes of chronic airway obstruction, such as neoplasms and
      tracheal scarring, are often clinically apparent well prior to asphyxia. Causes
      of acute airway obstruction may not be as obvious to clinicians or investigators.
      These include infections, anaphylactic reactions, status asthmaticus,
      inhalational injuries, and aspirations, which may result in acute obstruction and
      sudden death. We report the deaths of 2 individuals, a 43-year-old female and a
      78-year-old female, both with adenocarcinoma. The 43-year-old was hospitalized
      with a stage III, poorly differentiated infiltrating ductal carcinoma of the
      breast metastatic to the lymph nodes. She was intubated to treat poor respiratory
      function and acidosis. A bronchoalveolar lavage was consistent with alveolar
      hemorrhage; no organisms were identified. Blood and "clot" were in her
      endotracheal tube, so the endotracheal tube was replaced. She became comatose and
      life support was withdrawn. At autopsy, a large red-gray thrombus obstructed the
      trachea and extended into the right bronchus. Microscopically, the entire clot
      was composed of fibrin, red blood cells, and some mucus. Findings of acute
      respiratory distress syndrome with hyaline membranes were identified. The cause
      of death was listed as acute respiratory distress syndrome with tracheobronchial
      thrombus. Experiencing a decline in mental status, the 78-year-old had metastatic
      adenocarcinoma of unknown primary. She developed sudden respiratory distress and
      an airway obstruction was discovered. After failure to relieve the obstruction,
      she decompensated and died. At autopsy, a large, red-gray thrombus obstructed the
      distal trachea and both bronchi. Microscopically, the thrombus was composed of
      fibrin, platelets, and red blood cells. The cause of death was asphyxia secondary
      to airway obstruction by thrombus. We present these 2 unusual cases of asphyxia
      and review of the literature focusing on asphyxia and the etiology of airway
      thrombi.

PMID- 16304465
TI  - DNA analysis of ingested tomato and pepper seeds.
AB  - Ingested food is one of the important types of forensic evidence obtained during
      a medicolegal autopsy. Many materials containing seeds pass through the human
      digestive system and are still recognizable; thus, they can be valuable for
      providing investigative leads. Currently, the identification of seeds relies on
      microscopic and morphologic examination. However this method sometimes can be
      problematic. For example, the microscopic appearance of the ingested tomato and
      pepper seeds is very similar; thus, it is not always easy to distinguish these
      seeds by comparing their physical characteristics. Tomato and pepper seeds were
      selected as a model system to assess the value of performing DNA analysis as an
      alternate and/or complimentary means of seed identification. Results of blind
      testing indicate that the deoxyribonucleic acid-amplified fragment length
      polymorphism (DNA-AFLP) results were able to discriminate between pepper and
      tomato seed samples after they passed through the digestive system.

PMID- 16304466
TI  - Integrating the Accreditation Council for Graduate Medical Education general
      competencies into forensic pathology fellowship training.
AB  - Since July 2004, forensic pathology fellowships have been required to provide
      training in 6 general competencies: patient care, medical knowledge, practice
      based learning and improvement, interpersonal and communication skills,
      professionalism, and systems-based practice. In anticipation of this movement,
      beginning in 2002 the Office of the Medical Investigator (OMI) of the state of
      New Mexico began incorporating specific training in the general competencies into
      the fellowship program. Our experience has shown that the additional instruction
      and evaluation have proven to be valuable in preparing fellows for a successful
      forensic pathology career, did not detract from the more traditional aspects of
      forensic pathology training, and in many instances improved our training and
      assessment procedures.

PMID- 16304467
TI  - The forensic and investigative significance of reverse paternity testing with
      absent maternal sample.
AB  - The authors are involved in the extraction of DNA material from calcified
      tissues, oftentimes teeth, and analysis of such material to assist the
      investigative process, frequently by confirming the identity of the victim.
      Biologic or molecular techniques for the purposes of human identification have
      evolved to allow increasingly discriminating tests for use in criminal and
      noncriminal death investigations, as well as paternity disputes. The goal of such
      tests is to either include 2 samples (ie, they are from the same person, or in
      the case of paternity, they are from related individuals) or exclude 2 samples
      (ie, they are from different people or from unrelated individuals). Regardless of
      the system used and when data error has been eliminated, an exclusionary
      conclusion is irrefutable. The probability of excluding the falsely accused has
      steadily increased over the years as new methods are developed. Conventional ABO
      blood typing, for example, has a probability of exclusion (PE) of only 17%. This
      value increases to 53% with the inclusion of the Rh and MN systems. Additional
      serological markers can provide a probability of exclusion of greater than 99%.
      Today, the current method of choice for human identification is the polymerase
      chain reaction for the amplification of short tandem repeat (STR) multiplexes.
      This paper discusses the implications of nonpaternity in reverse paternity
      testing when only paternal DNA is available.

PMID- 16304468
TI  - Iatrogenic deaths following treatment for hypertrophic obstructive
      cardiomyopathy: case reports and an approach to the autopsy and death
      certification.
AB  - Hypertrophic cardiomyopathy (HCM) is a disease process which results in a large,
      heavy heart, with hypertrophy of the interventricular septum (IVS) and left
      ventricle. HCM accounts for a significant number of cases of sudden cardiac death
      each year, most infamously in young athletes. The prevalence of the disease has
      increased over the past several years due to advances in clinical diagnosis and
      molecular genetic studies. Over this same period, new forms of treatment also
      have emerged. One such treatment is alcohol septal ablation (ASA). ASA is a
      procedure performed by a cardiologist, via cardiac catheterization, by injecting
      pure ethanol into selected arteries which supply the IVS, resulting in a targeted
      myocardial infarction. This infarct then retracts and forms a scar, decreasing
      the outflow obstruction and improving the patient's clinical symptoms.The authors
      report 2 cases of death following ASA treatment of HCM. The first, a 56-year-old
      male, had his ASA procedure 10 days prior to death. The second decedent, a 76
      year-old female, had her procedure only 30 hours before death. These case reports
      are followed by a discussion about HCM, including pathology, treatments, and
      treatment-related pathology, before closing with a discussion about death
      certification in the cases presented and therapy-related deaths in general.

PMID- 16304469
TI  - Sudden cardiac death in a young woman: tumor of the atrioventricular (AV) node or
      citalopram intoxication?
AB  - Atrioventricular (AV) node tumor is a very rare lesion of the cardiac conduction
      system. Clinically, it is associated with complete AV block and sudden cardiac
      death, often in apparently healthy young people. We report a case of a 24-year
      old woman who developed ventricular fibrillation during sexual intercourse and
      died before admittance to the hospital. The woman had a medical history of
      depression and was treated with citalopram.At first, no macroscopic or
      microscopic pathologic changes were found. Toxicologic analysis showed a toxic
      level of citalopram in the blood. Further microscopic examination of the cardiac
      conduction system disclosed a tumor of the AV node. Immunohistochemical staining
      confirmed endodermal origin in accordance with the latest hypothesis of the
      pathogenesis of this tumor. It was concluded that this young woman died of
      cardiac arrhythmia due to the AV tumor and not from citalopram intoxication, as
      first suspected. This case emphasizes the importance of a microscopic examination
      of the cardiac conduction system in cases of sudden unexpected death, even in
      cases with a plausible cause and manner of death at first glance.

PMID- 16304470
TI  - Case report of a fatal intoxication by citalopram.
AB  - Citalopram is an antidepressant drug within the group of the selective serotonin
      reuptake inhibitors (SSRI). It is widely prescribed both in Europe and in United
      States, and it has always been considered a "safe" drug as pure intoxication with
      lethal outcome is rare, and most cases of overdose, even with high doses of
      citalopram ingested, are reported to have an uneventful course. We report the
      case of a young woman found dead at home. She had been prescribed citalopram by
      her family doctor 3 weeks before her death for a depressive syndrome. Police
      found in her house 3 empty blister packages of 28 citalopram tablets (20 mg) and
      2 bottles of citalopram oral solution (4%, 15 mL each). The autopsy findings were
      unremarkable. Nasal swabs, blood from femoral vein, urine, bile and tissue
      samples were collected for toxicologic investigation. Citalopram separation was
      performed by solid/liquid method, using Bond-Elute columns. The extracts were
      analyzed by GLC and GC/MS methods. The toxicologic analysis showed high levels of
      citalopram in all the examined fluids and tissue samples (blood concentration:
      11.60 mg/L). No other drugs and alcohol were detected. Our data confirm that if
      no other drug is involved, fatal complications occur only after ingestion of very
      high doses. However, there is no predefined "toxic dose," and the conditions
      under which the overdose occurs can be very important. We report the exact
      concentrations of the citalopram in the organs, and wethink that this can be
      useful in the cases where the blood samples were not available (ie, carbonized or
      decomposed body).

PMID- 16304471
TI  - Autoerotic accident by inhalation of propane-butane gas mixture.
AB  - We present a case of an accidental autoerotic death involving the inhalation of a
      propane-butane gas mixture, also known as LPG (liquefied petroleum gas). A 19
      year-old male was found dead in supine position in his bed in a residential
      accommodation one day after he was last seen alive. On a personal computer at the
      end of the bed, a pornographic movie was still running. On his left shoulder, an
      empty rubber balloon and on the bedside 2 empty "Kisag-Gas" cartridges were
      found. Toxicologic investigations revealed an intoxication with propane and
      butane, together with a recent consumption of cannabis. This case report compares
      the toxicologic findings with other recently published cases, and the theories of
      the toxic effects are discussed.

PMID- 16304472
TI  - Adipocere in postmortem imaging using multislice computed tomography (MSCT) and
      magnetic resonance imaging (MRI).
AB  - A body was found in a local river almost completely converted into adipocere. The
      corpse was identified as a 78-year-old male who was missed for 13 months. It was
      assumed that he committed suicide by drowning. The postmortem imaging findings
      utilizing multislice computed tomography (MSCT) and magnetic resonance imaging
      (MRI) in this virtopsy case are presented with special focus on the radiologic
      appearance of adipocere. The loss of signal in MRI and hyperdensities in MSCT up
      to 1000 Hounsfield units, as well as the increased assessment of the intracranial
      structures compared with traditional autopsy, are presented.

PMID- 16304473
TI  - Medicolegal aspects of an unusual uterine perforation with multiload-Cu 375R.
AB  - Perforation of the uterus is one of the most serious complications associated
      with insertion of intrauterine contraceptive devices (IUD). According to recent
      studies, this lesion occurs in 0.87 per 1000 cases, but statistics generally
      fluctuate between 0.05 and 13 per 1000 insertions. "Primary" perforations occur
      at the time of IUD insertion, and "secondary," or delayed, perforations are
      usually assumed to be caused by reactive uterine contractions. We report an
      unusual case of uterine perforation, which occurred 9 days after the insertion of
      a Multiload-Cu 375 IUD. The criteria for differential diagnosis between primary
      and secondary complications are discussed, particularly from the perspective of
      medical malpractice cases.

PMID- 16304474
TI  - Fatal venlafaxine overdose with acinar zone 3 liver cell necrosis.
AB  - We present a case of fatal venlafaxine overdose in a 34-year-old male with a
      history of depression and previous suicide attempts. He presented unwell, and his
      condition deteriorated with the development of rhabdomyocytolysis and renal
      failure. Although treatment was provided, this was unsuccessful, and he died
      within a day of his admission. A postmortem examination was performed, and the
      findings included an acinar zone 3 pattern of liver cell necrosis and a very high
      level of serum venlafaxine in the deceased. No other elevated drug levels were
      detected. From this case, it is clear that venlafaxine overdose was the primary
      cause of a fatal acinar zone 3 pattern of liver cell necrosis. As far as we are
      aware, this is the first reported case of fatal acinar zone 3 liver necrosis
      caused by venlafaxine overdose alone.

PMID- 16304475
TI  - Molecular autopsy of sudden cardiac death (SCD): the challenge of forensic
      pathologist to the complexity of genomics.

PMID- 16304476
TI  - High-resolution whole-body magnetic resonance image tumor staging with the use of
      parallel imaging versus dual-modality positron emission tomography-computed
      tomography: experience on a 32-channel system.
AB  - OBJECTIVE: The objective of this study was to compare the accuracy in staging of
      various malignant tumors with whole-body magnetic resonance imaging (WB-MRI)
      using parallel imaging (PAT) and positron emission tomography-computed tomography
      (PET-CT). MATERIALS AND METHODS: In a prospective study, 41 patients
      withoncologic diseases underwent [F]-fluoro-2-deoxy-D-glucose PET-CT for tumor
      staging and WB-MRI on a 32-channel-scanner with the use of PAT. Coronal T1w and
      STIR sequences at 5 body levels, axial HASTE imaging of the lung, and contrast
      enhanced T1w sequences of the liver, brain, and abdomen were performed. TNM stage
      was assessed for both modalities in a separate consensus reading using histologic
      results and radiologic follow up within 6 months as the standard of reference.
      RESULTS: Three primary and 4 recurrent tumors were detected; one recurrent tumor
      was missed with WB-MRI. Sixty benign and 60 malignant lymph nodes were detected
      with a sensitivity of 98% and specificity of 83% for PET-CT and 80%/75% for WB
      MRI, respectively. One hundred ninety-one malignant and 77 benign distant lesions
      were detected with a sensitivity/specificity of 82% for PET-CT and 96%/82% for WB
      MRI. Accuracy for correct TNM staging was 96% for PET-CT and 91% for WB-MRI.
      CONCLUSION: WB-MRI and PET-CT are reliable imaging modalities for tumor staging.
      WB-MRI is highly sensitive in detecting distant metastases; PET-CT is superior in
      lymph node staging. PAT makes high-resolution WB-MRI feasible within less than 1
      hour.

PMID- 16304477
TI  - Magnetic resonance imaging of the body trunk using a single-slab, 3-dimensional,
      T2-weighted turbo-spin-echo sequence with high sampling efficiency (SPACE) for
      high spatial resolution imaging: initial clinical experiences.
AB  - PURPOSE: The authors conducted a clinical evaluation of single-slab, 3
      dimensional, T2-weighted turbo-spin-echo (TSE) with high sampling efficiency
      (SPACE) for high isotropic body imaging with large field-of-view (FoV). MATERIALS
      AND METHODS: Fifty patients were examined in clinical routine with SPACE (regions
      of interest: pelvis n=30, lower spine n=12, upper spine n=6, extremities n=4) at
      1.5 T. For achieving a high sampling efficiency, parallel imaging, high
      turbofactor, and magnetization restore pulses were used. In contrast to a
      conventional TSE imaging technique with constant flip angle refocusing, the
      refocusing pulse train of the SPACE sequence consists of variable flip angle
      radiofrequency pulses along the echo train. RESULTS: Signal-to-noise ratio and
      contrast-to-noise ratio of SPACE images were of sufficient diagnostic value. The
      possibility of image reconstruction in multiple planes was of clinical relevance
      in all cases and simplified data analysis. CONCLUSION: The achievement of 3
      dimensional, T2-weighted TSE magnetic resonance imaging with isotropic and high
      spatial resolution and interactive 3-dimensional visualization essentially
      improve the diagnostic potential of magnetic resonance imaging.

PMID- 16304478
TI  - Dynamic computed tomography of the neonatal lung: volume calculations and
      validation in an animal model.
AB  - PURPOSE: The purpose of this study was to evaluate and validate dynamic volume
      calculation by respiratory-gated multislice computed tomography (CT) in small
      neonatal animals. MATERIALS AND METHODS: Six mechanically ventilated newborn
      piglets were imaged in a multislice CT with 0.5-mm slice thickness (4:16 pitch,
      0.5-second rotation time, 120 kV). The respirator was connected to the CT unit
      for recording the respiratory signal. Simultaneously, tidal volume was measured
      by the respirator and functional residual capacity (FRC) using a multiple-breath
      washin-washout technique (MBW) with heptafluoropropane (HFP) as tracer gas.
      Complete volume datasets were reconstructed throughout the respiratory cycle in
      increments of 10% using retrospective half-scan gating. All animals were scanned
      in 3 different ventilator settings. Dynamic lung volumes (tidal volumes) were
      calculated by means of segmentation of the lung parenchyma during the respiratory
      cycle using work-in-progress software. RESULTS: The mean (+/-standard deviation)
      FRC determined by CT was 24.7+/-8.6 mL versus 24.8+/-7.3 mL for the MBW
      technique. There was no statistically significant difference (P=0.555). Pearson's
      correlation coefficient showed a strong correlation between the data obtained
      with CT and that obtained with the MBW technique (r=0.886). After exclusion of
      one outlier, tidal volumes showed a similar correlation (r=0.837) without
      significant differences in the mean values (CT: 8.9+/-2.4 mL and respirator:
      8.7+/-2.4 mL, P=0.566). CONCLUSION: Dynamic multislice CT with respiratory gating
      allows for calculation of lung volumes and may be useful for future CT
      applications in human neonatal lung imaging.

PMID- 16304479
TI  - Changes in first-pass interstitial kinetics of DTPA in myocardium submitted to
      low-flow ischemia.
AB  - OBJECTIVES: This study aimed to determine the changes during ischemia in the
      myocardial first-pass kinetics of DTPA, an extracellular tracer that is currently
      used for assessing myocardial perfusion with magnetic resonance imaging
      (Magnevist). MATERIALS AND METHODS: Using an indicator-dilution technique, first
      pass kinetics of DTPA were compared between normoxia (n=11) and low-flow ischemia
      (n=11) in isolated rabbit hearts perfused with red blood cell-enhanced perfusate.
      RESULTS: There was no difference between ischemia and normoxia in the
      interstitial extraction and clearance rates of DTPA. Interstitial distribution
      volume of DTPA was, however, lower in ischemia than in normoxia (in percent of
      myocardial volume: 15+/-11% vs 25+/-11%, P=0.02) as a result of a relationship
      with coronary flow (P<0.001). CONCLUSIONS: During low-flow myocardial ischemia,
      DTPA kinetics are unchanged, except for the interstitial distribution volume that
      is decreased, presumably because of the shrinkage of extracellular fluid. These
      kinetic properties are favorable for detecting myocardial ischemia at rest with
      magnetic resonance imaging.

PMID- 16304480
TI  - Specific absorption rate as a poor indicator of magnetic resonance-related
      implant heating.
AB  - Recent publications of the magnetic resonance safety profile of neurostimulators,
      cardiac pacemakers, and other implanted devices imply that these devices are no
      longer a contraindication for magnetic resonance imaging. It is very promising
      that patients who have these implanted devices may in the future no longer be
      denied an important diagnostic modality. On the other hand, the safety
      recommendations given in a number of publications included the maximum
      permissible whole-body specific absorption rate (SAR). This is one factor
      indicating potential heating, but there are a number of other factors that may
      have an even higher impact on the potential heating of tissue in the vicinity of
      leads or implanted devices. Using only the whole-body SAR as a recommendation for
      a safety profile is potentially dangerous.

PMID- 16304481
TI  - Variability in densitometric assessment of pulmonary emphysema with computed
      tomography.
AB  - OBJECTIVES: The objectives of this study were to investigate whether computed
      tomography (CT) densitometry can be applied consistently in different centers;
      and to evaluate the reproducibility of densitometric quantification of emphysema
      by assessment of different sources of variation, ie, intersite, interscan and
      inter- and intraobserver variability, in comparison with intersubject
      variability. MATERIALS AND METHODS: In 5 different hospitals, 119 patients with
      emphysema were scanned using standardized protocols. In each site, an observer
      performed a quantitative densitometric analysis (including blood recalibration)
      on the corresponding patient group (n=23-25) and one observer analyzed the entire
      group of 119 patients. After several months, the latter observer analyzed all
      data for a second time. Subsequently, different sources of variation were
      assessed by variance component analysis with and without volume correction of the
      data. RESULTS: Inter- and intraobserver variability marginally contributes to the
      total variability (<0.001%). The interscan variability was 0.02% of the total
      variation after application of volume correction. The intersite variability was
      48% as a result of one deviating CT scanner. Air recalibration normalized
      deviating air densities in CT scanners. Within sites, the intersubject
      variability ranged between 93% and 99% based on the analysis of 2 subsequent CT
      scans of the patients. CONCLUSIONS: Almost all variability in the density
      measurement of emphysema originates from differences between scanners and from
      differences in severity of emphysema between patients. Lung densitometry with
      multislice CT scanners is a highly reproducible measurement, especially if
      corrected for lung volume, because this reduces interscan variability.

PMID- 16304482
TI  - A longitudinal study of R2* and R2 magnetic resonance imaging relaxation rate
      measurements in murine liver after a single administration of 3 different iron
      oxide-based contrast agents.
AB  - OBJECTIVE: The objective of this study was to investigate the duration of R2* and
      R2 enhancement in murine liver in vivo after administration of a single dose of 3
      different iron oxide-based contrast agents. MATERIALS AND METHODS: Murine liver
      R2* and R2 were quantified longitudinally postadministration of 2.5 mgFe/kg
      ferumoxides, 2.5 mgFe/kg ferumoxytol, 2.5 or 5 mgFe/kg feruglose, or saline over
      50 days. Changes in R2* and R2 were evaluated histologically using Perl's
      staining and by atomic absorption spectrometry. RESULTS: All 3 contrast agents
      significantly increased liver R2* and R2 4 hours after challenge. After 10 days,
      R2* and R2 for both the ferumoxides and ferumoxytol cohorts had recovered to
      saline control levels, whereas the faster R2* and R2 of the feruglose cohort was
      sustained and significantly faster than control at day 50. Histology revealed
      feruglose in both Kupffer and endothelial cells, whereas both ferumoxides and
      ferumoxytol were associated with the Kupffer cells. CONCLUSION: Compared with
      ferumoxides and ferumoxytol, feruglose exhibits prolonged R2* and R2 enhancement
      of murine liver.

PMID- 16304483
TI  - Brain tumor enhancement in magnetic resonance imaging: comparison of signal-to
      noise ratio (SNR) and contrast-to-noise ratio (CNR) at 1.5 versus 3 tesla.
AB  - OBJECTIVE: The objective of this study was to compare the difference in lesion
      enhancement between 1.5 and 3 T using an extracellular gadolinium chelate in a
      rat brain glioma model. METHODS: Five rats (CDF Fischer 344) with implanted
      C6/LacZ brain gliomas were evaluated using matched T1-weighted spin echo
      techniques and hardware configurations at 1.5 and 3 T. Serial imaging over 10
      minutes after gadoteridol (ProHance) administration was performed. Contrast
      enhancement (CE), signal-to-noise ratios (SNR) for brain and tumor, as well as
      contrast-to-noise ratios (CNR) were evaluated using region-of-interest (ROI)
      analysis at both field strengths. All gliomas were also evaluated by
      histopathology. RESULTS: CE at 3 T increased by 106% to 137% (all P<0.05) with
      maximum CE occurring at 5 minutes for both 1.5 and 3 T (9.8+/-2.2 vs 21.1+/-3.5;
      P=0.0004). At 3 T, SNR increased for normal brain by 66% to 76% (P<0.01) and SNR
      for tumor increased by 70% to 89% (P<0.01). CNR increased by 101% to 137%
      (P<0.05) depending on the time postcontrast. The highest CNR for both 1.5 T and 3
      T occurred 5 minutes after contrast (1.5 T: 9.4+/-1.1 vs 3 T: 20.3+/-2.4;
      P<0.0004). CONCLUSION: Using a standardized animal model and matched scan
      techniques, this study shows a significant benefit of 3 T compared with 1.5 T in
      contrast-enhanced brain tumor magnetic resonance imaging.

PMID- 16304484
TI  - Advances in magnetic resonance (2005).

PMID- 16304485
TI  - Pathophysiologic aspects of major depression following traumatic brain injury.
AB  - Mood disorders, particularly major depression, are the most frequent complication
      of traumatic brain injury. Major depression is present in about 40% of patients
      hospitalization for a traumatic brain injury. Anxiety disorders, substance abuse,
      dysregulation of emotional expression, and aggressive outbursts are frequently
      associated with major depression, and their coexistence constitutes a marker of a
      more disabling clinical course. The complex interactions of genetic,
      developmental, and psychosocial factors determine patients' vulnerability to
      developing affective disturbances following a traumatic brain injury. Symptoms of
      depression cluster into the domains of low mood and distorted self-attitude, lack
      of motivation and anhedonia, subjective cognitive complaints, and hyperactive and
      disinhibited behavior. It is reasonable to assume that these symptomatic clusters
      have specific underlying mechanisms that need to be integrated in a comprehensive
      pathophysiologic model.

PMID- 16304486
TI  - Early impaired self-awareness, depression, and subjective well-being following
      traumatic brain injury.
AB  - OBJECTIVE: To examine the incidence and intercorrelation of early impaired self
      awareness (ISA) and depression after traumatic brain injury (TBI), as well as
      their contributions to prediction of patients' subjective well-being at discharge
      from inpatient rehabilitation. DESIGN: Inception cohort. SETTING: Inpatient
      rehabilitation. PATIENTS: Subjects were 96 patients with TBI seen for inpatient
      rehabilitation at the Methodist Rehabilitation Center. All subjects had emerged
      from posttraumatic amnesia prior to assessment for this study. INTERVENTION:
      None. MAIN OUTCOME MEASURE: Subjective well-being as measured by the Satisfaction
      With Life Scale taken at discharge from inpatient rehabilitation. RESULTS:
      Multivariable linear regression analysis revealed that ISA and functional status
      (Disability Rating Scale total score) at rehabilitation admission made
      independent contributions to prediction of subjective well-being. Bivariable
      correlational analyses demonstrated that frequency of depressive symptoms was
      inversely correlated with Satisfaction With Life Scale scores. Impaired self
      awareness and depression were not correlated in this sample. CONCLUSIONS: Results
      support the idea that ISA is an important factor in determining subjective well
      being in patients with TBI at acute rehabilitation discharge. Early interventions
      to decrease ISA may improve patients' functional status at rehabilitation
      discharge.

PMID- 16304487
TI  - Validity of the Patient Health Questionnaire-9 in assessing depression following
      traumatic brain injury.
AB  - OBJECTIVE: To test the validity and reliability of the Patient Health
      Questionnaire-9 (PHQ-9) for diagnosing major depressive disorder (MDD) among
      persons with traumatic brain injury (TBI). DESIGN: Prospective cohort study.
      SETTING: Level I trauma center. PARTICIPANTS: 135 adults within 1 year of
      complicated mild, moderate, or severe TBI. MAIN OUTCOME MEASURES: PHQ-9
      Depression Scale, Structured Clinical Interview for Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition (SCID). RESULTS: Using a screening
      criterion of at least 5 PHQ-9 symptoms present at least several days over the
      last 2 weeks (with one being depressed mood or anhedonia) maximizes sensitivity
      (0.93) and specificity (0.89) while providing a positive predictive value of 0.63
      and a negative predictive value of 0.99 when compared to SCID diagnosis of MDD.
      Pearson's correlation between the PHQ-9 scores and other depression measures was
      0.90 with the Hopkins Symptom Checklist depression subscale and 0.78 with the
      Hamilton Rating Scale for Depression. Test-retest reliability of the PHQ-9 was r
      = 0.76 and kappa = 0.46 when using the optimal screening method. CONCLUSIONS: The
      PHQ-9 is a valid and reliable screening tool for detecting MDD in persons with
      TBI.

PMID- 16304488
TI  - Evaluation of the Neurobehavioral Functioning Inventory as a depression screening
      tool after traumatic brain injury.
AB  - OBJECTIVE: To examine the utility of the Neurobehavioral Functioning Inventory
      (NFI) for diagnosing depression in a rehabilitation setting. DESIGN: In a
      prospective study, a structured clinical interview (Structured Clinical Interview
      for DSM-IV-TR) was used to identify DSM-IV-defined major depressive disorder
      (MDD) symptoms among patients with traumatic brain injury (TBI). NFI Depression
      scale items were compared with DSM-IV diagnosis obtained by the Structured
      Clinical Interview for DSM-IV Axis I Disorders. SETTING: Outpatient
      neuropsychology clinic at a university hospital, private outpatient physical
      medicine and rehabilitation clinic, and a long-term specialized living assistance
      program. PARTICIPANTS: Participants consisted of 78 patients with TBI who were at
      least 3 months postinjury and 18 years of age or older. MAIN OUTCOME MEASURES:
      Structured Clinical Interview for DSM-IV Axis I Disorders and the NFI. RESULTS:
      Psychiatric diagnostic interview with the Structured Clinical Interview for DSM
      IV Axis I Disorders indicated that 50% of patients with TBI in our sample had at
      least one of the following in their lifetime: MDD, MDD due to general medical
      condition, dysthymia, or adjustment disorder with depressed mood. Thirty percent
      met diagnostic criteria for current MDD with or without general medical
      condition. Analyses of the NFI items revealed that individuals with depression
      endorsed greater levels of problems than did those without depression on 14 of
      the 32 items related to the DSM-IV symptom domains for depression (P < .00156
      with Bonferroni correction). In predicting the diagnosis of depression using
      individual NFI items, the classification rate based on the Random Forests
      estimate was 83%. CONCLUSION: Findings indicate that the NFI items differentiated
      between depressed and nondepressed patients with TBI. Imposing minimal burden on
      patients and staff, the NFI appears to have good predictive value in diagnosing
      major depression. In clinical practice and research, the NFI is a potentially
      valuable screening tool for identifying major depression in persons with TBI.

PMID- 16304489
TI  - The role of self-discrepancy theory in understanding post-traumatic brain injury
      affective disorders: a pilot study.
AB  - This pilot study examined the utility of self-discrepancy theory (SDT) in
      explaining post-traumatic brain injury (TBI) depression and anxiety. The SDT
      model was expanded to include the discrepancy between the postinjury self and the
      preinjury self. Study participants were 21 individuals with mild to severe TBI
      residing in the community, who completed the Selves Interview, the Selves
      Adjective Checklist, the Beck Depression Inventory-II and the Beck Anxiety
      Inventory. Strong correlations were found between affective distress and self
      discrepancies, as measured by the checklist. Scores on the interview were not
      related to affective distress. The findings suggest that further research is
      merited to examine the utility of the SDT in addressing issues of post-TBI
      depression and anxiety.

PMID- 16304490
TI  - Treatment of depression following traumatic brain injury.
AB  - Depression is a common consequence of traumatic brain injury (TBI), and is a
      source of substantial distress and disability for persons with TBI and their
      families. This article offers a practical approach to the evaluation and
      treatment of this condition. Diagnostic and etiologic considerations relevant to
      this issue are reviewed first. Next, somatic therapies for posttraumatic
      depression, including antidepressant medications and electroconvulsive therapy,
      are discussed. Use of these therapies is also considered in the context of the
      common medical and neurological comorbidities among persons with TBI. Finally,
      psychosocial interventions relevant to the care of persons with posttraumatic
      depression are presented.

PMID- 16304491
TI  - Botulinum neurotoxin in muscle overactivity.

PMID- 16304492
TI  - Editorial.

PMID- 16304494
TI  - Critical decisions in selecting an intravenous immunoglobulin product.
AB  - Use of intravenous immunoglobulin (IVIG) therapy has expanded enormously in the
      past two to three decades, targeting a large number of autoimmune and
      inflammatory disorders as well as primary immunodeficiency disease, human
      immunodeficiency virus, and Kawasaki disease. Increased use, particularly at
      higher doses and in older patients, has presented certain challenges related to
      safety and tolerability. All IVIGs are not the same. They differ in manufacturing
      processes, methods of virus elimination, and final composition. Carefully
      evaluating patient risk factors and matching them to potential IVIG product risks
      and benefits are becoming increasingly important in the selection of a particular
      IVIG.

PMID- 16304495
TI  - Care and management of intrathecal and epidural catheters.
AB  - Epidural and intrathecal catheters have increasingly become a part of acute and
      chronic pain management over the past 25 years. Externalized systems include
      temporary, permanent exteriorized, and permanent port systems for use over weeks
      to months of expected therapy. Implanted, completely internalized systems are
      available for conditions expected to require many months or years of therapy.
      Expert care includes routine management as well as advanced troubleshooting.
      Prevention of infection is a key priority for nurses managing these devices.

PMID- 16304496
TI  - Juvenile idiopathic arthritis: why do I have to hurt so much?
AB  - In the current world of high-tech medicine, some individuals nevertheless
      experience immeasurable chronic pain daily. Among these are 60,000 to 70,000
      children in the United States who have juvenile idiopathic arthritis. The
      children affected by this disease experience a decreased quality of life and
      sometimes blindness. Outcome severity in these cases is related directly to the
      amount of injury to bones, joints, soft tissue, and eyes at the time of
      diagnosis. There are not enough specialists to ensure timely diagnosis and
      medications, and although the symptoms of juvenile idiopathic arthritis are
      treatable, there is no cure. Until timely diagnosis and treatment can be ensured,
      pain and blindness will continue to be the daily experience of these children.

PMID- 16304497
TI  - End-of-life care with the heart failure patient in home health: a case study.
AB  - The diagnosis of congestive heart failure accounts for a large proportion of
      hospital admissions and multiple readmissions over the course of the disease.
      During the end stage of their disease process, patients often are prescribed many
      complex medications such as inotropic infusion therapy. For a patient to receive
      an intravenous medication at home, there must be a collaborative approach between
      nurse, family, patient, and physician. This palliative approach can result in
      decreased hospital admissions and an improved quality of life for patients with
      end-stage congestive heart failure.

PMID- 16304498
TI  - How often should peripheral intravenous catheters in ambulatory patients be
      flushed?
AB  - Ambulatory intravenous (IV) treatment is frequently prescribed to be administered
      every 24 hours. Institutional protocols commonly recommend flushing catheters
      every 8 hours. The authors sought to identify whether flushing more than once
      every 24 hours conferred any benefit. A retrospective review compared
      complication rates of different catheter flushing intervals for patients
      receiving IV therapy. This study investigated 111 courses of treatment for 63
      patients. In 43% of the patients (48/111), complications were identified during
      the treatment period. Complications were less common with flushing every 24 hours
      (39/99, 39.4%) than with more frequent flushing (9/12, 75%) (P = .021).
      Indwelling peripheral IV catheters flushed once every 24 hours appear to have
      lower complication rates than those flushed 2 or 3 times a day.

PMID- 16304505
TI  - Strategies for improving adherence to second-generation antipsychotics in
      patients with schizophrenia by increasing ease of use.
AB  - Despite the advances in the treatment of patients with schizophrenia that have
      occurred since the introduction of the second-generation (atypical) antipsychotic
      agents, a leading cause of suboptimal outcome is poor patient adherence to oral
      medication. Partial adherence can be attributed to a number of factors, including
      lack of insight, cognitive dysfunction, a complicated treatment regimen, drug
      related side effects, patient attitude, lack of patient education, and cultural
      factors. A number of strategies, including psychosocial interventions, cognitive
      behavioral techniques, strategies that minimize side effects, and pharmacological
      approaches that increase ease of medication use, can be employed to support
      adherence and improve long-term outcomes. This article focuses on strategies for
      increasing ease of use of antipsychotics in the treatment of patients with
      schizophrenia. These strategies include using monotherapy rather than
      polypharmacy, simplifying the medication regimen, and using a long-acting
      antipsychotic formulation. The goal of these strategies is to improve adherence
      and help prevent relapse by ensuring continuous antipsychotic coverage.
      Strategies that optimize ease of use of medication treatment for schizophrenia
      and thus improve adherence to treatment are likely to promote the attainment of
      new treatment goals and improved patient outcomes.

PMID- 16304504
TI  - Effects of personality disorders on functioning and well-being in major
      depressive disorder.
AB  - BACKGROUND: Patients with depressive disorders have limitations in physical and
      emotional functioning comparable to patients with chronic medical conditions.
      Personality disorders (PDs) are also known to be associated with functional
      impairment. AIMS: To determine the effects of PDs on the functioning and well
      being of patients with major depressive disorder (MDD). METHOD: In the
      Collaborative Longitudinal Personality Disorders Study, 668 patients who met
      criteria for schizotypal, borderline, avoidant, or obsessive-compulsive PDs or
      for MDD and no PD were assessed with semi-structured interviews at baseline, 6,
      12, 24, and 36 months. In this study, 151 patients who met criteria for current
      MDD at the 36-month follow-up were compared on the basis of the presence (n =
      118) or absence (n = 33) of persistent PD. Physical and social/emotional
      functioning and well-being were assessed using the Medical Outcomes Study (MOS)
      Short-Form Health Survey (SF-36). These results were compared with those of a
      sample of patients with MDD seen in the mental health specialty sector who were
      followed in the Medical Outcomes Study. RESULTS: Patients with MDD and co
      occurring PD had significantly more impairment on scales measuring role
      limitations due to emotional problems, social functioning, and general health
      perceptions than patients with MDD and no PD. Although patients with MDD and no
      PD were found to have levels of functioning and well-being that were lower in
      several domains than those previously reported in depressed patients recruited
      from mental health settings, patients with MDD and co-occurring PD were found to
      have much lower levels of functioning in all areas than reported samples.
      CONCLUSIONS: Co-occurring PDs contribute significantly to impairment in social
      and emotional functioning and reduced well-being in patients with MDD.

PMID- 16304506
TI  - Increasing lifestyle physical activity in patients with depression or other
      serious mental illness.
AB  - People with severe and persistent mental illness are more likely to be overweight
      and to suffer from obesity-related illnesses such as diabetes and heart disease
      than healthy individuals. Lifestyle change interventions that emphasize
      integrating physical activity into daily life have not been studied extensively
      in people with mental illness. The authors present the results of an initial
      feasibility study of a lifestyle modification program for individuals with
      serious mental illness. Thirty-nine individuals with depression or other serious
      mental illness were recruited from three different mental health facilities to
      attend an 18-week lifestyle intervention program promoting physical activity and
      healthy eating. At each session, participants discussed topics related to healthy
      lifestyle changes and participated in group walks. Data were collected at
      baseline, 6 weeks, and 18 weeks. The results demonstrated that individuals who
      have depression and other serious mental illnesses can participate in a lifestyle
      intervention program. Participants who attended the final follow-up session had
      lost weight over the course of the intervention. Study retention was a problem.
      However, the cost of this type of group-based lifestyle intervention was
      relatively low, so that such an intervention for this high-risk group may still
      be cost-effective.

PMID- 16304507
TI  - Depression in pregnancy and the postpartum period: balancing adverse effects of
      untreated illness with treatment risks.
AB  - The author reviews the risks and benefits of untreated maternal depression during
      pregnancy and the postnatal period and its effects on the well-being of the
      mother and infant. She then discusses the significant role psychiatrists can play
      in detecting and managing maternal depression as a primary measure for preventing
      future child psychopathology. A literature search was conducted on PubMed to
      identify both preclinical and clinical studies concerning deleterious effects of
      maternal depression on offspring. Additional searches focused on available safety
      data concerning the use of antidepressants during pregnancy and lactation. Key
      search items included depression during pregnancy, postpartum depression,
      lactation, and antidepressants. Burgeoning evidence was found concerning the
      adverse effects of maternal depression on the developing fetus and infant in the
      perinatal period. No controlled studies on the safety of antidepressant use in
      pregnancy and lactation were found; therefore, case reports, and some
      retrospective and prospective case series, must serve as guidelines for the
      treating clinician. Each case of maternal depression needs to be evaluated on an
      individual basis and decisions about treatment interventions should involve both
      the patient and family. Maternal depression during pregnancy and the postnatal
      period is associated with a significant disease burden in that it affects not
      only the mother but may also have both short- and long-term effects on offspring.
      Therefore, early detection and management of maternal depression, of which
      perinatal screening of mothers is an important component, are warranted.

PMID- 16304508
TI  - Drug-drug interactions: Proof of relevance (Part II): cause of tolerability
      problems or noncompliance.

PMID- 16304509
TI  - Compulsive personalities and Ingmar Bergman's Wild Strawberries.

PMID- 16304510
TI  - Forensic aspects of e-therapy.

PMID- 16304514
TI  - Aesthetic and reconstructive brow lift: current techniques, indications, and
      applications.

PMID- 16304511
TI  - A case of "ifufunyane": a xhosa culture-bound syndrome.

PMID- 16304515
TI  - Unilateral frontalis sling for the surgical correction of unilateral poor
      function ptosis.
AB  - PURPOSE: To evaluate the functional and cosmetic results after frontalis sling
      repair for unilateral ptosis associated with either poor levator function or
      synkinesis. METHODS: Preoperative and postoperative photographs and records of
      127 patients who underwent unilateral frontalis sling ptosis repair were
      retrospectively reviewed. An eyelid crease incision was used in all cases, with
      suturing of the sling material directly to tarsus. RESULTS: Preoperative
      diagnosis for all patients was either unilateral poor-function blepharoptosis or
      ptosis associated with levator synkinesis. Underlying causes included 75
      congenital, 13 posttraumatic, 11 congenital "jaw-winking," 10 cranial nerve III
      palsies, 9 myasthenia gravis, 5 chronic progressive external ophthalmoplegia, and
      4 congenital "double-elevator" palsies. There was a mean follow-up of 11.6
      months. Twenty-eight eyelids required reoperation: 11 for undercorrection, 6 for
      overcorrection with keratopathy, 2 for upper eyelid crease revision, 7 for
      correction of poor contour, 1 for a broken sling, and 1 for removal of an
      infected exposed polytetraflouroethylene sling. Lagophthalmos of greater than 2
      mm was noted in 18 patients, 5 of whom had persistent keratopathy requiring
      reoperation. No other complications were reported, except for 1 suture granuloma.
      Good to excellent final postoperative eyelid height was achieved in 121 patients
      (95%) after all surgeries and with conscious recruitment of the frontalis muscle.
      A large majority of patients and/or parents expressed satisfaction with the final
      cosmetic result and were not bothered by any asymmetric lagophthalmos in downgaze
      or lack of a synchronous blink. However, 19 of 25 amblyopic patients were less
      satisfied with passive eyelid height as they failed to recruit the ipsilateral
      frontalis muscle to activate the sling during binocular viewing. In 17 of these
      19 patients, good to excellent eyelid height could be achieved with conscious
      active brow elevation. CONCLUSIONS: Unilateral sling provides good to excellent
      functional and cosmetic results in unilateral poor-function ptosis. However,
      patients with amblyopia usually require conscious effort to activate the
      frontalis muscle to achieve satisfactory eyelid height.

PMID- 16304517
TI  - Corrugator superciliaris muscle excision for tension and migraine headaches.
AB  - PURPOSE: This study investigates the effect of corrugator superciliaris muscle
      excision on patients with frequent tension or chronic migraine headaches
      emanating from the glabellar or frontal regions. METHODS: We present a
      prospective study of 12 patients with chronic and frequent tension and/or
      migraine headaches. Patients who had already elected to undergo corrugator
      excision for cosmesis (n = 64) were given questionnaires to evaluate for the
      presence of chronic, recurrent migraine and/or tension headaches. Patients who
      answered in the affirmative went on to answer questions such as onset, location,
      frequency, severity, and duration of their headaches. Patients were grouped by
      types of headaches: tension, migraine, and combined headaches. Twelve patients
      who met all criteria were entered into the study and underwent corrugator
      excision in combination with blepharoplasty. Postoperative questionnaires and
      interviews were administered to evaluate the response of the patients' headaches
      to corrugator excision. RESULTS: All 12 patients had less frequent headaches and
      said they would have the procedure performed again for headache. Eleven of 12
      patients (92%) had less intense headaches after corrugator superciliaris
      excision. Overall, 58% noted complete relief of their headaches. Follow-up ranged
      from 6 to 19 months. CONCLUSIONS: Corrugator superciliaris muscle excision
      provides significant relief for headaches emanating from or localizing to the
      frontal and glabellar regions. Although improvement of migraine headaches has
      been previously described with this technique, this is the first report, to our
      knowledge, of effective surgical treatment of tension headaches by corrugator
      excision.

PMID- 16304518
TI  - Treatment of congenital nasolacrimal duct obstruction with high-pressure
      irrigation under topical anesthesia.
AB  - PURPOSE: To evaluate the effectiveness, safety, and success rate of high-pressure
      irrigation (HPI) applied under topical anesthesia in outpatient treatment of
      congenital nasolacrimal duct obstruction. METHODS: HPI was applied under topical
      anesthesia to 39 eyes of 32 consecutive patients with congenital nasolacrimal
      duct obstruction. If obstructive symptoms persisted after the first attempt,
      treatment was repeated within 1 month. Patients were divided in two age groups: 7
      to 12 months and 12 to 18 months. The two groups were compared in terms of the
      number of attempts needed to resolve the obstruction. RESULTS: Thirty-nine eyes
      that had failed conservative treatment underwent high-pressure irrigation. The
      overall success rate was 31 of 39 (79.48%) at the first attempt; complete success
      (8/8, 100%) was achieved at the second attempt. The success rate in the younger
      group was 18 of 22 (81.8%) at the first attempt and 4 of 4 (100%) at the second
      attempt. The success rate in the older group was 13 of 17 (76.5%) at the first
      attempt and 4 of 4 (100%) at the second attempt. There was no statistically
      significant difference between the two groups regarding the number of attempts
      needed to relieve the symptoms (p > 0.05). There was no statistically significant
      difference in massage times and age between cases resolved at the first and
      second attempts (p > 0.05). CONCLUSIONS: HPI can be attempted as an alternative
      second-step treatment or as a transition procedure between conservative and
      invasive methods. HPI has the advantage of being less invasive than other
      secondary methods, and its application under topical anesthesia seems to be safe
      and effective.

PMID- 16304519
TI  - Effect of exophthalmometer design on its accuracy.
AB  - PURPOSE: To investigate the effect of the design of different exophthalmometers
      on their measurement accuracy. METHODS: Eight different exophthalmometers were
      tested with a specially developed calibrator by experienced orbital surgeons.
      RESULTS: Exophthalmometers with one mirror and a straight footplate were found to
      be more accurate than others. One-mirror exophthalmometers were less accurate
      when assessing low (< or =12 mm) and high (> or =23 mm) exophthalmometric values.
      CONCLUSIONS: The design of an exophthalmometer affects its accuracy.

PMID- 16304520
TI  - Hertel curve: orbital volume increment and proptosis in a cadaver model.
AB  - PURPOSE: This study examined the relation between effective orbital volume
      increment and proptosis induced by an inflatable orbital implant in a human
      cadaver orbit. METHODS: A 25-ml inflatable latex balloon was inserted between the
      periorbita and orbital floor in 15 human cadavers. Hertel measurements were taken
      for each milliliter over a total 7-ml volume increment. Five trials per orbit for
      15 cadavers resulted in 525 data points. RESULTS: Average exophthalmos per
      milliliter of volume increment was plotted over 7 ml, using 1-ml volume
      increments. The resultant curve, which was termed a Hertel curve, was linear over
      7 ml (R > 99%) and had a slope of 0.62 mm per milliliter of volume increment.
      CONCLUSIONS: An inflatable orbital implant is an effective tool for introducing a
      specified amount of volume in the cadaver orbit. The predictable relation between
      proptosis and volume increment (Hertel curve) may be a useful tool for surgeons
      in planning the size of an implant required to surgically correct enophthalmos.

PMID- 16304521
TI  - Orbital invasion by esthesioneuroblastoma.
AB  - PURPOSE: Esthesioneuroblastoma is a rare malignancy arising from the olfactory
      mucosa in the nasal fossa, which can invade the orbit producing ophthalmic
      symptoms and signs. The purpose of this study was to present a case series and
      review the literature to assess the characteristics of orbital involvement by
      esthesioneuroblastoma. METHODS: Retrospective case series of all patients treated
      for biopsy-proven esthesioneuroblastoma at the Royal Adelaide Hospital between
      1992 and 2004. RESULTS: Nine patients (5 male, 4 female) with a mean age of 50
      years (range, 20 to 66 years) were reviewed. One case was classified as Kadish
      stage A, 1 as Kadish stage B, and 7 as Kadish stage C. Mean time from onset of
      symptoms to diagnosis was 17 months (range, 2 to 24 months). Radiologic orbital
      invasion was present in 4 cases and was associated with ophthalmic symptoms or
      signs in 3 of these cases. These included proptosis (2 cases), periorbital pain
      (1 case), decreased visual acuity (1 case), extraocular muscle restriction (1
      case), and chemosis (1 case). One patient with symptoms secondary to orbital
      invasion was initially referred to and assessed by an ophthalmologist. All
      patients who had or went on to have development of orbital invasion had advanced
      disease at diagnosis. Treatment was surgical (9/9), with the addition of
      radiotherapy (6/9) and chemotherapy (2/9). Mean follow-up was 3.6 years (range,
      0.5 to 8.5 years). Six of 9 patients had tumor recurrence. Two had metastasis.
      Five of 9 patients remained alive. CONCLUSIONS: Orbital invasion by
      esthesioneuroblastoma is not uncommon. It is important to be aware of this
      malignancy because a significant proportion of patients will present with
      ophthalmic signs and symptoms.

PMID- 16304523
TI  - Massive congenital orbital teratoma.
AB  - Orbital teratomas are rare embryonic tumors composed of a wide diversity of
      tissues derived from the three germinal layers. The presenting features include,
      a healthy newborn with extreme unilateral proptosis; marked stretching of the
      eyelids over a tense, fluctuating mass, with elongation of the palpebral fissure;
      enlargement of the bony orbit (two to three times normal size) with subsequent
      nasal and malar deformities; and transillumination of all or part of the orbital
      mass. Commonly the eye is normally developed but often vision is not preserved
      either due to exposure or secondary optic atrophy. The objective in the
      management of orbital teratoma is to save the eye to encourage orbitofacial
      development, maintain cosmesis and retain some vision. We report a case of
      massive congenital orbital teratoma successfully removed by an eyelid-sparing
      exenteration technique.

PMID- 16304522
TI  - Bilobed flap in ophthalmic plastic surgery: simple principles for flap
      construction.
AB  - This report describes simple principles for constructing the bilobed flap in the
      periocular region. The results in a prospective series of 23 consecutive patients
      are presented. All patients achieved satisfactory functional and aesthetic
      results with the use of this technique. These simple principles achieved
      consistently good results and can enable the surgeon to use this flap with
      greater confidence.

PMID- 16304524
TI  - Orbital perforating branch of the infraorbital artery: an important landmark in
      orbital surgery.
AB  - The orbital branch of the infraorbital artery is an important surgical landmark
      but is frequently omitted from texts that discuss orbital anatomy and surgical
      technique. This report reviews the anatomy of this artery to familiarize the
      reader with its existence and location to reduce the risk of intraoperative
      hemorrhage from this vessel.

PMID- 16304525
TI  - Primary orbital Ewing sarcoma in a middle-aged man.
AB  - A 54-year-old man presented with a painful left proptosis and a soft tissue mass
      at the inferolateral aspect of the left orbit with bone involvement. There was no
      clinical or investigational evidence of systemic disease. Both light microscopy
      and immunohistochemistry were required for the diagnosis of Ewing sarcoma. After
      failure of chemotherapy alone, management included extensive surgical excision
      and postoperative adjuvant radiotherapy and chemotherapy. Despite intervention,
      the patient died of widespread metastatic disease 17 months after initial
      presentation. Although rare, Ewing sarcoma should be included in the differential
      diagnosis of uniform round cell orbital tumors in adults.

PMID- 16304526
TI  - Primary orbital leiomyosarcoma.
AB  - An 84-year-old woman presented with a right upper eyelid nodule, first noted 1
      month earlier. Incisional biopsy revealed leiomyosarcoma, which was subsequently
      treated with wide excision and adjunctive radiotherapy. There has been no
      evidence of tumor recurrence in 3 years of follow-up.

PMID- 16304527
TI  - Imaging of metastatic orbital leiomyosarcoma.
AB  - A 74-year-old man with a previous history of lower leg soft tissues
      leiomyosarcoma and multiple metastasis presented with a progressive painless
      proptosis of the left eye. Orbital ultrasound, CT, and MRI revealed a large mass
      in the left medial orbit. The mass was surgically removed and pathologic
      examination confirmed the diagnosis of a metastatic orbital leiomyosarcoma. The
      imaging characteristics of this rare tumor are comprehensively detailed, using
      complementary ultrasound, CT, and MRI, the combination of which allowed planning
      of total excision of the lesion.

PMID- 16304528
TI  - Rhabdomyosarcoma masquerading as acute dacryocystitis.
AB  - An 11-year-old boy presented with right medial canthal swelling. He was initially
      diagnosed with dacryocystitis and treated with oral antibiotics, followed by
      incision and drainage of a presumed lacrimal sac abscess. Rapid recurrence of the
      swelling led to further clinical evaluation, including a maxillofacial CT, which
      revealed an extensive nasal and orbital mass that was consistent with embryonal
      rhabdomyosarcoma on histopathologic analysis. This represents an unusual case of
      rhabdomyosarcoma manifesting as acute dacryocystitis. Rhabdomyosarcoma should be
      considered in the differential diagnosis for acquired nasolacrimal obstruction
      and dacryocystitis in the pediatric population.

PMID- 16304529
TI  - Orbital lymphoma with concomitant sarcoid-like granulomas.
AB  - A 41-year-old man presented with chronic eyelid swelling, conjunctival injection,
      and decreased ocular motility in all gaze directions. MRI showed bilateral
      enlarged extraocular muscles, including the tendons. Laboratory tests revealed
      elevated levels of angiotensin-converting enzyme. An orbital biopsy showed
      collections of monotonous small lymphocytes, and granulomatous inflammation that
      included multinucleated giant cells, predominantly Langhans type. Flow cytometric
      analysis of tissue demonstrated a light chain-restricted clonal population of B
      cells, a finding that confirmed the morphologic impression of lymphoma. This case
      demonstrates that elevated angiotensin-converting enzyme and granulomatous
      inflammation can occur in lymphoma. Careful histopathologic examination and flow
      cytometric analysis are essential to avoid an erroneous diagnosis that could lead
      to inappropriate management.

PMID- 16304530
TI  - Multiple cavernous hemangiomas presenting as orbital apex syndrome.
AB  - A 41-year-old man presented with a 7-year history of gradually increasing right
      proptosis and a 2-year history of decreased vision and limited eye movements.
      Right proptosis (11 mm), limitation of movement in all gazes, anisocoria, and
      visual impairment implied orbital apex compression. Computed tomography showed
      several distinct lesions with mild delayed enhancement extending to the orbital
      apex. Through a lateral orbitotomy, 10 discrete hemangiomas were removed
      uneventfully. Histopathologic findings were consistent with cavernous hemangioma
      in all tumors removed. Proptosis resolved after surgery at 3 to 4 weeks. Visual
      acuity was unchanged (20/25), and eye movement significantly improved at last
      follow-up, 15 months after surgery.

PMID- 16304531
TI  - Giant cell reparative granuloma of the orbit.
AB  - This report describes a case of an orbital giant cell reparative granuloma in an
      85-year-old woman. Giant cell reparative granulomas are fibro-osseous benign
      proliferations typically found in the jawbones and rarely in the orbital bones.
      All previously described cases in the orbit have been in younger patients,
      classically in the third to fourth decades.

PMID- 16304532
TI  - Severe subcutaneous emphysema following orbital blowout fracture.
AB  - A 19-year-old man sustained a blowout fracture to the left orbital floor.
      Subcutaneous emphysema developed after a protracted sneezing episode. Some signs
      of respiratory distress ensued, and the patient was emergently intubated. He
      underwent surgical repair of the fracture and then had further extension of the
      subcutaneous emphysema. The left nasal cavity was packed and the emphysema slowly
      resolved. Clinically significant subcutaneous emphysema is an uncommon
      complication of orbital blowout fracture. Informing the patient to avoid
      excessive nose-blowing and to avoid occluding the nose while sneezing may prevent
      this complication.

PMID- 16304533
TI  - Cranio-orbital injury with internal carotid artery laceration and a missing
      eyelid.
AB  - A 37-year-old man presented to the emergency department with a visor impacted in
      the left orbit after a motorbike accident. His initial injury appeared to be
      limited to the orbit. Because the bleeding appeared disproportionate to the
      orbital injury, an intracranial injury was suspected. Subsequently, on
      hemicraniotomy, the tip of the visor was found at the bifurcation of the internal
      carotid artery. The avulsed upper eyelid was found under the frontal lobe. The
      patient underwent the clipping of internal carotid artery and middle and anterior
      cerebral artery with replantation of the upper eyelid. Neurologic damage was
      limited to loss of vision, right foot drop, and bowel and bladder incontinence.
      This case of penetrating orbital trauma demonstrates that the absence of focal
      neurologic deficit and radiologic signs suggestive of intracranial injury may not
      rule out life-threatening intracranial injury.

PMID- 16304534
TI  - Use of an electromagnet to retrieve a broken fascia needle during frontalis sling
      surgery.
AB  - Frontalis sling surgery was performed on a 2-year-old girl with congenital
      ptosis. During surgery, the tip of the Wright fascia needle broke off as it was
      being passed between incisions within the eyebrow. The tip was difficult to
      locate and retrieve through the original incision and was finally located with an
      electromagnet and removed through an enlarged incision.

PMID- 16304536
TI  - Re: "Customized, single-incision, 3-wall orbital decompression".

PMID- 16304538
TI  - Re: "Monocanalicular versus bicanalicular silicone intubation for nasolacrimal
      duct stenosis in adults".

PMID- 16304539
TI  - Re: "Horizontal eyelid movement on eyelid closure".

PMID- 16304541
TI  - Re: "Horizontal eyelid movement on eyelid closure".

PMID- 16304542
TI  - Re: "Enucleation with primary implant for treatment of recalcitrant
      endophthalmitis and panophthalmitis".

PMID- 16304544
TI  - Re: "Cerebral vasospasm and ischemia after orbital decompression for Graves
      ophthalmopathy".

PMID- 16304553
TI  - Screening HIV-infected persons for tuberculosis--Cambodia, January 2004-February
      2005.
AB  - Worldwide, tuberculosis (TB) is one of the most common causes of death among
      persons infected with human immunodeficiency virus (HIV). The World Health
      Organization recommends screening HIV-infected persons for TB disease after HIV
      diagnosis, before initiation of highly active antiretroviral therapy (HAART), and
      during routine follow-up care. In 2003, health officials in Banteay Meanchey
      Province, Cambodia, in conjunction with CDC and the U.S. Agency for International
      Development (USAID), began a pilot project to increase TB screening among persons
      with HIV infection. Subsequently, CDC analyzed and evaluated data from the first
      14 months of the project. This report summarizes the results of that analysis,
      which determined that, during January 2004--February 2005, among persons with HIV
      infection at voluntary counseling and confidential testing (VCCT) clinics, 37%
      were screened for TB disease, and 24% of those screened had TB disease diagnosed.
      On the basis of these findings, the Provincial Health Department (PHD) took
      action to increase awareness of the risk for TB among HIV-infected persons.
      During the 3 months after these measures were implemented, the TB screening rate
      among persons with HIV infection increased to 61%. Evaluation of projects like
      the one conducted in Banteay Meanchey Province can help develop an evidence-based
      approach for removing barriers to screening HIV-infected persons for TB.

PMID- 16304554
TI  - Dental visits among dentate adults with diabetes--United States, 1999 and 2004.
AB  - One of the major complications of diabetes is periodontal disease, a chronic
      infection of tissues supporting the teeth and a major cause of tooth loss. Adults
      with diabetes have both a higher prevalence of periodontal disease and more
      severe forms of the disease, contributing to impaired quality of life and
      substantial oral functional disability. In addition, periodontal disease has been
      associated with development of glucose intolerance and poor glycemic control
      among adults with diabetes. Regular dental visits provide opportunities for
      prevention, early detection, and treatment of periodontal disease among dentate
      adults (i.e., those having one or more teeth); moreover, regular dental cleaning
      improves glycemic control in patients with poorly controlled diabetic conditions.
      One of the national health objectives for 2010 is to increase the proportion of
      persons with diabetes who have an annual dental examination to 71% (revised
      objective 5-15). To estimate the percentage of dentate U.S. adults aged > or =18
      years with diabetes who visited a dentist within the preceding 12 months, CDC
      analyzed data from the Behavioral Risk Factor Surveillance System (BRFSS) surveys
      for 1999 and 2004. This report describes the results of that analysis, which
      indicated that, in 2004, age-adjusted estimates in only seven states exceeded 71%
      and estimated percentages for four states and District of Columbia (DC) increased
      significantly from their levels in 1999. The findings underscore the need to
      increase awareness and support for oral health care among adults with diabetes,
      including support for national and state diabetes care management programs.

PMID- 16304555
TI  - Mobility limitation among persons aged > or =40 years with and without diagnosed
      diabetes and lower extremity disease--United States, 1999-2002.
AB  - Diabetes increases the risk for mobility limitation, especially among older
      persons. Lower extremity disease (LED), which includes peripheral arterial
      disease (PAD) and peripheral neuropathy (PN), also increases the risk for
      mobility limitation. To assess the prevalence of mobility limitation among
      persons with diagnosed diabetes, persons with LED, and persons with both or
      neither condition, CDC analyzed data from the National Health and Nutrition
      Examination Survey (NHANES) 1999-2002 for adults aged > or =40 years. This report
      summarizes the preliminary findings, which indicated that the national prevalence
      of mobility limitation is higher among persons with either diagnosed diabetes or
      LED than those without the conditions, and that adults with both conditions have
      a higher prevalence of mobility limitation than those with either condition
      alone. Monitoring the prevalence of diabetes, LED, and associated risk factors
      and identifying effective LED prevention strategies will help reduce the burden
      of mobility limitation in the United States.

PMID- 16304556
TI  - Abortion surveillance--United States, 2002.
AB  - PROBLEM/CONDITION: CDC began abortion surveillance in 1969 to document the number
      and characteristics of women obtaining legal induced abortions. REPORTING PERIOD
      COVERED: This report summarizes and describes data voluntarily reported to CDC
      regarding legal induced abortions obtained in the United States in 2002.
      DESCRIPTION OF SYSTEM: For each year since 1969, CDC has compiled abortion data
      by state or area of occurrence. During 1973-1997, data were received from or
      estimated for 52 reporting areas in the United States: 50 states, the District of
      Columbia, and New York City. In 1998 and 1999, CDC compiled abortion data from 48
      reporting areas. Alaska, California, New Hampshire, and Oklahoma did not report,
      and data for these states were not estimated. For 2000-2002, Oklahoma again
      reported these data, increasing the number of reporting areas to 49. RESULTS: A
      total of 854,122 legal induced abortions were reported to CDC for 2002 from 49
      reporting areas, representing a 0.1% increase from the 853,485 legal induced
      abortions reported by the same 49 reporting areas for 2001. The abortion ratio,
      defined as the number of abortions per 1,000 live births, was 246 in 2002, the
      same as reported for 2001. The abortion rate was 16 per 1,000 women aged 15-44
      years for 2002, the same as for 2001. For the same 48 reporting areas, the
      abortion rate remained relatively constant during 1997-2002. The highest
      percentages of reported abortions were for women who were unmarried (82%), white
      (55%), and aged <25 years (51%). Of all abortions for which gestational age was
      reported, 60% were performed at < or =8 weeks' gestation and 88% at <13 weeks.
      From 1992 (when detailed data regarding early abortions were first collected)
      through 2002, steady increases have occurred in the percentage of abortions
      performed at < or =6 weeks' gestation. A limited number of abortions was obtained
      at >15 weeks' gestation, including 4.1% at 16-20 weeks and 1.4% at > or =21
      weeks. A total of 35 reporting areas submitted data stating that they performed
      and enumerated medical (nonsurgical) procedures, accounting for 5.2% of all known
      reported procedures from the 45 areas with adequate reporting on type of
      procedure. INTERPRETATION: During 1990-1997, the number of legal induced
      abortions gradually declined. When the same 48 reporting areas were compared, the
      number of abortions decreased during 1996-2001, then slightly increased in 2002.
      In 2000 and 2001, even with one additional reporting state, the number of
      abortions declined slightly, with a minimal increase in 2002. PUBLIC HEALTH
      ACTION: Abortion surveillance in the United States continues to provide the data
      necessary for examining trends in numbers and characteristics of women who obtain
      legal induced abortions and to increase understanding of this pregnancy outcome.
      Policymakers and program planners use these data to improve the health and well
      being of women and infants.

PMID- 16304557
TI  - Three months' treatment with the alpha1-blocker alfuzosin does not affect total
      or transition zone volume of the prostate.
AB  - Treatment with alpha(1)-adrenergic receptor blockers improves lower urinary tract
      symptoms (LUTS) secondary to benign prostatic hyperplasia. This study was
      conducted to test the hypothesis that induction of apoptosis in prostate tissue
      could be a mechanism underlying the observed clinical benefit. This placebo
      controlled, double-blind, randomized trial enrolled 536 men with LUTS who were
      treated with alfuzosin (10 or 15 mg) once daily or placebo for 3 months. Total
      prostate and transition zone volume was measured by standardized transrectal
      ultrasound measurements at baseline and 3 months. Total prostate volume increased
      by 0.4 ml from baseline in placebo patients but decreased by -0.25 ml in the
      combined alfuzosin groups. Percentage change was not statistically significantly
      different between the placebo and alfuzosin groups. Changes in transition zone
      volumes from baseline were similar in both treatment arms; percentage change was
      not statistically significantly different between the placebo and alfuzosin
      groups. Volume changes did not correlate with prostate volumes at baseline.
      Overall, neither total prostate nor transition zone volume increased or decreased
      systematically within the 3-month treatment period. If alfuzosin-induced
      apoptosis in prostate tissue, it was not evident by a measurable change in
      prostate volume after 3 months' treatment. Further analysis at 1 and 2 years will
      determine the effect of longer-term treatment.

PMID- 16304558
TI  - Loss of heterozygosity of M6P/IGF2R gene is an early event in the development of
      prostate cancer.
AB  - BACKGROUND: The genetic events leading to initiation and/or progression of
      prostate cancer are not well characterized. The gene coding for the mannose 6
      phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) has recently been
      identified as a tumor suppressor in several types of cancer. The purpose of the
      present study is to determine whether the M6P/IGF2R gene is inactivated in human
      prostate cancer, and if so, whether this is an early or late transformational
      event. METHODS: In total, 43 patients with prostate cancer treated by radical
      prostatectomy, with archival material available for analysis, were assessed for
      loss of heterozygosity (LOH) in the M6P/IGF2R gene using six different gene
      specific nucleotide polymorphisms. Regions of tumor, normal prostate and
      premalignant high-grade prostate intraepithelial neoplasia (PIN) were identified
      and cells were excised by laser capture microdissection (LCM). DNA segments were
      amplified using polymerase chain reaction (PCR). RESULTS: The M6P/IGF2R gene was
      polymorphic in 83.7% (36/43) of patients, and 41.7% (15/36) of these informative
      patients had LOH in the tumor tissue. In 11/15 patients with LOH in malignant
      tissue, high-grade PIN could be identified, and 63.6% (7/11) also had LOH in this
      premalignant tissue. CONCLUSIONS: This study is the first to find that the
      M6P/IGF2R gene is inactivated in prostate cancer. LOH in premalignant tissue as
      well suggests that mutation in the M6P/IGF2R gene is an early event in the
      development of prostate cancer, supporting the conclusion that it functions as a
      tumor suppressor gene in this disease.

PMID- 16304559
TI  - Antibody levels against BK virus and prostate, kidney and bladder cancers in the
      EPIC-Oxford cohort.
AB  - In a case-control study nested within the EPIC-Oxford cohort, there were no
      statistically significant differences in the prevalence or titre of antibodies
      against BK virus measured in plasma taken prior to diagnosis between cases with
      cancer of the prostate (n=31), kidney (n=5) or bladder (n=9) and controls (n=45).

PMID- 16304561
TI  - Rehospitalization following compensable work-related tetraplegia.
AB  - DESIGN: Descriptive study. OBJECTIVES: To document the characteristics of
      rehospitalization following work-related tetraplegia, investigate risk factors
      for rehospitalization and identify opportunities for rehospitalization
      prevention. SETTING: Workers' compensation administrative database with national
      coverage. METHODS: The administrative database of a large workers' compensation
      provider was searched for work-related tetraplegia claims with dates of injury
      between 1 January 1989 and 31 December 1999. In all, 61 cases were identified
      where detailed rehospitalization information was available. Medical payment data
      were extracted, rehospitalization reasons were coded, and rates, costs and length
      of stay were calculated. RESULTS: In all, 62% of cases were rehospitalized at
      some time during the period for which data were available. The average number of
      days the study group spent rehospitalized per year was 9.2 and the average annual
      cost was 14,197 US dollars. The most common reasons for rehospitalization were
      dermatological (23%), orthopedic (18%) and urological (14%). It was found that as
      many as 74% of the total number of days persons spent rehospitalized, 64% of the
      monies spent on rehospitalization, and 47% of rehospitalizations could have been
      prevented. CONCLUSIONS: Consistent with earlier research, the ability to identify
      risk factors for rehospitalization was limited. However, the current study does
      highlight the extent to which rehospitalizations disrupt the lives of people with
      work-related tetraplegia and that a substantial proportion of rehospitalizations
      can be avoided. SPONSORSHIP: The research was supported, in part, by a grant from
      the National Institute on Disability and Rehabilitation Research National Model
      SCI Systems (Grant no. H133N00024).

PMID- 16304562
TI  - Decompression surgery for lumbar spinal stenosis in the elderly: preoperative
      expectations and postoperative satisfaction.
AB  - STUDY DESIGN: Retrospective cohort examination. OBJECTIVES: Data on expectations
      and satisfaction rates in elderly patients operated for lumbar spinal stenosis
      (LSS) are limited. The present study aimed to investigate these issues as well as
      the factors that might affect them. SETTING: A university affiliated hospital.
      PATIENTS AND METHODS: A follow-up study of 367 consecutive patients aged 65 years
      and older (mean age 71.4 years), who underwent surgery for degenerative LSS
      between 1990 and 2000. Data collection included patients' preoperative
      expectation, demographic data, body mass index, operative risk, duration of
      symptoms, clinical presentation and patients' satisfaction on follow-up, pain
      level, activities of daily living level and walking ability. Data were recorded
      before operation and on follow-up. Preoperative and follow-up data were analyzed
      by univariate and multivariable models. RESULTS: The response rate on follow-up
      was 81% (298 patients). A logistic regression analysis showed that advanced age,
      male gender and high education level were independently associated with positive
      expectations, while a great number of covariates were associated with patients'
      satisfaction. High patients' expectations were positively interrelated with
      satisfaction (r=0.332, P<0.001). CONCLUSIONS: In the elderly, preoperative
      expectations reasonably predict their postoperative satisfaction rate. It is
      suggested that a greater effort should be made to narrow the gaps between
      expectations and satisfaction, perhaps by providing more accurate preoperative
      information data regarding the outcomes of planned surgery.

PMID- 16304563
TI  - Review of spinal cord injuries in Ireland.
AB  - STUDY DESIGN: Prospective data collection on all patients with spinal cord injury
      (SCI) admitted for a comprehensive management programme. OBJECTIVES: To examine
      the epidemiology of SCI in Ireland over 1 year. SETTING: Ireland's National
      Spinal Cord Injury Centre. METHODS: Systematic data collection on all patients
      admitted with SCI for management. RESULTS: A total of 46 patients (40 males) were
      admitted from January to December 2000; median age was 37 years (range 6-82
      years). In all, 23 of the patients presented with cervical injuries, 19 patients
      had thoracic injuries. In all, 18 patients had complete injuries (American spinal
      injuries association (ASIA)). Motor vehicle collisions were the cause of 50% of
      SCI. CONCLUSIONS: The incidence of SCI in Ireland is 13.1 per million population.
      Demographic data from this study can go towards improving care for patients with
      SCI and also in the prevention of SCI.

PMID- 16304564
TI  - Orthostatic hypotension following spinal cord injury: understanding clinical
      pathophysiology.
AB  - Motor and sensory deficits are well-known consequences of spinal cord injury
      (SCI). During the last decade, a significant number of experimental and clinical
      studies have focused on the investigation of autonomic dysfunction and
      cardiovascular control following SCI. Numerous clinical reports have suggested
      that unstable blood pressure control in individuals with SCI could be responsible
      for their increased cardiovascular mortality. The aim of this review is to
      outline the incidence and pathophysiological mechanisms underlying the
      orthostatic hypotension that commonly occurs following SCI. We describe the
      clinical abnormalities of blood pressure control following SCI, with particular
      emphasis upon orthostatic hypotension. Possible mechanisms underlying orthostatic
      hypotension in SCI, such as changes in sympathetic activity, altered baroreflex
      function, the lack of skeletal muscle pumping activity, cardiovascular
      deconditioning and altered salt and water balance will be discussed. Possible
      alterations in cerebral autoregulation following SCI, and the impact of these
      changes upon cerebral perfusion are also examined. Finally, the management of
      orthostatic hypotension will be considered.

PMID- 16304565
TI  - Improving walking assessment in subjects with an incomplete spinal cord injury:
      responsiveness.
AB  - STUDY DESIGN: Prospective longitudinal study. OBJECTIVES: To investigate the
      responsiveness of the Walking Index for Spinal Cord Injury II (WISCI II), 6-Min
      Walk (6MWT) and 10-Meter Walk Tests (10MWT) for the assessment of walking
      capacity in incomplete spinal cord injury (iSCI) and to validate these tests with
      the lower extremity motor score (LEMS). SETTING: European Multicenter Study of
      Human Spinal Cord Injury. METHODS: The walking tests of 22 iSCI subjects who
      achieved functional ambulation and could stand or walk within 1 month after iSCI
      were analyzed at 3, 6 and 12 months after injury. Responsiveness was assessed by
      determining differences between the time intervals, and Spearman's correlation
      coefficient was calculated to quantify validity. RESULTS: All walking tests were
      able to assess the improvement of walking capacity within the first 3 months
      after injury. Between 3 and 6 months, only the 10MWT and 6MWT were responsive to
      the ongoing improvement in locomotor capacity. Overall, correlations between the
      tests were good within the first month, but became poorer over time. CONCLUSION:
      The 6MWT and 10MWT were more responsive in demonstrating an improvement in
      walking capacity compared to the WISCI II. The testing of functional outcome
      after iSCI as provided by the ordinal ASIA motor score can be improved by
      interval scaled measures. This allows increasing the responsiveness of functional
      outcome measures and should be advantageous in assessing therapeutical approaches
      in iSCI subjects. In iSCI subjects with walking ability, we recommend the
      additional use of timed tests to monitor improvement in locomotor capacity.

PMID- 16304566
TI  - Spinal tuberculosis with concomitant spondylolisthesis: coexisting entities or
      'cause and effect'?
AB  - STUDY DESIGN: Report of three unusual cases of coexisting spondylolisthesis and
      tuberculosis in the same patient. OBJECTIVES: To document the rare occurrence and
      attempt to postulate the probable reasons for such an association. SETTING:
      Tertiary care teaching hospital in a developing country. METHODS: This
      communication reports the outcome of three cases where there was
      spondylolisthesis and spinal tuberculosis in the same patient. The probable
      reason for such an occurrence is discussed along with a literature review
      relevant to this topic. RESULTS: The cases responded favorably to conservative
      treatment with multidrug antitubercular chemotherapy and spinal braces.
      CONCLUSIONS: Association of spondylolisthesis and spinal tuberculosis is
      extremely rare. If the tubercular process is fulminant, spondylolisthesis
      secondary to destruction of posterior elements by the infective process can
      occur. Gross destruction of anterior elements secondary to tuberculosis in some
      patients may place excessive stresses on the posterior elements and may
      precipitate a spondylolisthesis even if there was no active infection in the
      posterior elements. However, there remains a distinct possibility that pars
      defect may have existed prior to infective pathology.

PMID- 16304567
TI  - Effects of repeated ejaculations on semen characteristics following spinal cord
      injury.
AB  - STUDY DESIGN: Prospective randomised controlled study. OBJECTIVE: To evaluate the
      effects of repeated ejaculation on semen characteristics following spinal cord
      injury (SCI) in a prospective randomised controlled study. SETTING: Spinal
      Research Centre, Stanmore, UK and Institute of Urology and Nephrology, London,
      UK. METHODS: A total of 74 patients with SCI above T10 were tested by vibro
      ejaculation using a Ferticare penile vibrator (Multicept A/S Horsholm, Denmark)
      using a standardised technique. The ejaculate was examined according to WHO
      protocol. The successfully vibro-ejaculated subjects (n = 32) were randomised
      into a study group (n = 18) and a control group (n = 14). The patients in the
      study group vibro-ejaculated weekly for 3 months with semen analysis performed at
      baseline and then monthly. The control group vibro-ejaculated at baseline and at
      the end of the 3-month period. Two experienced observers performed the semen
      analysis independently. All measures were compared for statistical significance
      across the two groups at the beginning and at the end of the 3-month period using
      a two-tailed student t-test. Significance was determined at the 95% confidence
      interval (P < 0.05). RESULTS: In total, 10 patients in the study group and nine
      in the control group have completed the study so far. Six patients have dropped
      out of the study group and three from the control group for varied reasons. Two
      patients are currently enrolled in the study and control groups. The morphology
      and forward progression of sperm shows a statistically significant increase in
      the study group. The motility improves but is not statistically significant in
      the study group. No significant adverse effects were reported. CONCLUSIONS: We
      have shown in this unique randomised controlled study that repeated ejaculation
      does improve the sperm characteristics in SCI patients. It is suggested that SCI
      men should undergo repeated ejaculation for at least 3 months before trying
      intravaginal or intrauterine insemination techniques. If this fails then in vitro
      fertilisation can be used. This method promotes natural conception, is intimate
      and cost effective.

PMID- 16304568
TI  - Spinal extradural meningeal cyst with spinal stenosis.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To present a rare pathology causing a
      common disease. SETTING: Spine unit of the orthopaedic surgery department of a
      university hospital in Berlin/Germany. CASE REPORT: A 39-year-old female with an
      intraspinal extradural arachnoid cyst of the lumbar spine presented with
      intermittent radiating lumbar pain. The magnetic resonance imaging (MRI) showed a
      dorsal spinal extradural arachnoid cyst at L3/4. After wide laminotomy L3,
      operative cyst resection and stabilisation at L3/4 by posterior lumbar interbody
      fusion (PLIF), major symptom relief occurred. CONCLUSION: Spinal extradural
      arachnoid cysts are a rare entity causing low back pain and intermittent
      radicular syndromes. They can be caused by arachnoid herniation through dural
      weak spots which are hereditary or occur after trauma. A ball-valve mechanism
      promotes growth. The main diagnostic tool for spinal extradural cysts is the MRI
      scan. Additionally, myelography is helpful to demonstrate fluid communication.
      Complete surgical removal of the cyst should be attempted to reduce risk of
      recurrence. If extensive decompression is needed for the surgical approach
      causing segmental instability, interbody fusion is recommended. The outcome
      depends on age, duration and degree of neurological damage.

PMID- 16304569
TI  - Pediatric acute myeloid leukemia: international progress and future directions.

PMID- 16304570
TI  - Treatment strategies and long-term results in paediatric patients treated in four
      consecutive AML-BFM trials.
AB  - A total of 1111 children with acute myeloblastic leukaemia (AML) were treated in
      four consecutive Berlin-Frankfurt-Munster (BFM) studies from 1978 to 1998. The
      first cooperative trial AML-BFM 78 established intensive chemotherapy with seven
      drugs, CNS irradiation and 2-year maintenance, achieving a long-term survival
      (overall survival (OS)) of 40%. Induction intensification in AML-BFM 83 resulted
      in significant improvement of disease-free survival (DFS). The risk of
      haemorrhage, especially in children with hyperleukocytosis, proved the high
      relevance of supportive care. In AML-BFM 87, the benefit of CNS irradiation in
      preventing CNS/systemic relapses was demonstrated. In AML-BFM 93, the
      introduction of idarubicin during first induction followed by intensification
      with HAM increased the 5-year EFS, DFS and OS to 50+/-2, 61+/-3 and 57+/-2%,
      respectively. Stem cell transplantation (SCT), as applied in high-risk patients
      with a matched related donor, did not significantly improve the outcome compared
      to chemotherapy alone. In spite of treatment intensification, the therapy-related
      death rate decreased from trial to trial, mainly during induction. The future aim
      is to reduce long-term sequelae, especially cardiotoxicity, by administration of
      less cardiotoxic drugs, and toxicity of SCT by risk-adapted indications. The AML
      BFM studies performed in three European countries with >70 cooperating centres
      have significantly improved the outcome in AML children; nevertheless, increasing
      experience with these intensive treatment regimens is of fundamental importance
      to reduce fatal complications.

PMID- 16304571
TI  - Long-term results in children with AML: NOPHO-AML Study Group--report of three
      consecutive trials.
AB  - In all, 447 children with acute myeloid leukaemia (AML) have been treated on
      three consecutive NOPHO studies from July 1984 to December 2001. NOPHO-AML 84 was
      of moderate intensity with an induction of three courses of cytarabine, 6
      thioguanine and doxorubicin followed by four consolidation courses with high-dose
      cytarabine. The 5-year event-free survival (EFS), disease free survival (DFS) and
      overall survival (OS) were 29, 37 and 38%. NOPHO-AML 88 was of high intensity
      with the addition of etoposide and mitoxantrone in selected courses during
      induction and consolidation. The interval between the induction courses should be
      as short as possible, that is, time intensity was introduced. The 5-year EFS, DFS
      and OS were 41, 48 and 46%. In NOPHO-AML 93, the treatment was stratified
      according to response to first induction course. The protocol utilised the same
      induction blocks as NOPHO-AML 88, but after the first block, children with a
      hypoplastic, nonleukaemic bone marrow were allowed to recover before the second
      block. Consolidation was identical with NOPHO-AML 88. The 5-year EFS, DFS and OS
      in NOPHO-AML 93 were 48, 52 and 65%. The new NOPHO-AML protocol has been based on
      experiences from previous protocols with stratification of patients with regard
      to in vivo response and specific cytogenetic aberrations.

PMID- 16304572
TI  - Treatment strategy and long-term results in paediatric patients treated in
      consecutive UK AML trials.
AB  - Between 1988 and 2002, 758 children with acute myeloid leukaemia (AML) were
      treated on Medical Research Council (MRC) AML 10 and AML 12. MRC AML 10 tested
      the role of bone marrow transplantation following four blocks of intensive
      chemotherapy and found that while both allogeneic bone marrow transplant (allo
      BMT) and autologous bone marrow transplant (A-BMT) significantly reduced the
      relapse risk (RR), this did not translate into a significant improvement in
      overall survival (OS). A risk group stratification based on cytogenetics and
      response to the first course of chemotherapy derived from MRC AML 10 was used to
      deliver risk-directed therapy in MRC AML 12. Allo-BMT was limited to standard and
      poor risk patients and A-BMT was not employed. Instead, the benefit of an
      additional block of treatment was tested by randomising children to receive
      either four or five blocks of treatment in total. While the results of MRC AML 12
      remain immature, there appears to be no survival advantage for a fifth course of
      treatment. The 5 year OS, disease-free survival (DFS), event-free survival (EFS)
      and RR in MRC AML 12 are 66, 61, 56 and 35%, respectively; at present superior to
      MRC AML 10, which had a 5-year OS, DFS, EFS and RR of 58, 53, 49 and 42%,
      respectively. MRC AML trials employ a short course of triple intrathecal
      chemotherapy alone for CNS-directed treatment and CNS relapse is uncommon.
      Improvements in supportive care have contributed to improved outcomes and the
      number of deaths in remission fell between trials. Anthracycline-related
      cardiotoxicity remains a concern and the current MRC AML 15 trial tests the
      feasibility of reducing anthracycline dosage without compromising outcome by
      comparing standard MRC anthracycline-based consolidation with high-dose ara-C.
      MRC studies suggest that the role of allo-BMT is limited in 1st CR and that there
      may be a ceiling of benefit from current or conventional chemotherapy.

PMID- 16304574
TI  - Acute myelogenous leukemia in Chile PINDA protocols 87 and 92 results.

PMID- 16304573
TI  - Treatment strategy and long-term results in pediatric patients treated in two
      consecutive AML-GATLA trials.

PMID- 16304575
TI  - Evidence for involvement of clonally expanded CD8+ T cells in anticancer immune
      responses in CLL patients following nonmyeloablative conditioning and
      hematopoietic cell transplantation.
AB  - We have analyzed the clonotype composition of CD8+ T cells following
      nonmyeloablative (NMA) conditioning and hematopoietic cell transplantation (HCT),
      of patients with chronic lymphocytic leukemia (CLL). Consecutive analyses of
      blood samples taken up to 2 years following HCT, demonstrated that CD8+ T-cell
      clonality was highly dynamic in the early phases after HCT, but became more
      stable after 4-5 months. Moreover, donor lymphocyte infusion (DLI) given for
      disease progression in one of the patients led to establishment of recurrent as
      well as new T-cell clonotypes. This coincided with disease remission, strongly
      suggesting that these T cells were engaged with anti-CLL cytotoxicity. To examine
      the functional capacity of stable clonally expanded T cells after HCT, CD8+ T
      cells isolated post-transplant from the recipients were stimulated ex vivo with
      CLL cells and subsequently analyzed by FACS for surface expression of the marker
      for cytotoxic activity, CD107a. Stimulation with CLL cells indeed led to surface
      expression of CD107a, and clonotype analyses of sorted cells demonstrated that
      CD107a positive T cells were stably expanded following HCT. Our data suggest that
      clonally expanded CD8+ T-cell clones participate in the ongoing T-cell response
      against CLL cells following HCT with NMA conditioning.

PMID- 16304576
TI  - Resistance to cytarabine and gemcitabine and in vitro selection of transduced
      cells after retroviral expression of cytidine deaminase in human hematopoietic
      progenitor cells.
AB  - Overexpression of the detoxifying enzyme cytidine deaminase (CDD) renders normal
      and leukemic hematopoietic cells resistant to cytarabine (1-beta-D
      arabinofuranosylcytosine), and studies on murine cells have suggested transgenic
      CDD overexpression as a way to reduce the substantial myelotoxicity induced by
      the deoxycytidine analogs cytarabine and gemcitabine (2',2'
      difluorodeoxycytidine). We now have investigated CDD (over-)expression in the
      human hematopoietic system. Retroviral gene transfer significantly increased the
      resistance of CDD-transduced cord blood and peripheral blood-derived progenitor
      cells for doses ranging from 20-100 nM cytarabine and 8-10 nM gemcitabine.
      Protection was observed for progenitors of erythroid as well as myeloid
      differentiation, though the degree of protection varied for individual drugs. In
      addition, significant selection of CDD-transduced cells was obtained after a 4
      day culture in 30-100 nM cytarabine. Thus, our data demonstrate that
      overexpression of CDD cDNA results in significant protection of human progenitors
      from cytarabine- as well as gemcitabine-induced toxicity, and allows in vitro
      selection of transduced cells. This strongly argues for a potential therapeutic
      role of CDD gene transfer in conjunction with dose-intensive cytarabine- or
      gemcitabine-containing chemotherapy regimen.

PMID- 16304577
TI  - IgH/TCR rearrangements are common in MLL translocated adult AML and suggest an
      early T/myeloid or B/myeloid maturation arrest, which correlates with the MLL
      partner.

PMID- 16304578
TI  - Reply to van der Sluijs-Gelling et al.

PMID- 16304579
TI  - Treatment with granulocyte colony-stimulating factor ameliorates chronic heart
      failure.
AB  - Chronic heart failure remains a leading cause of mortality. Although granulocyte
      colony-stimulating factor (G-CSF) is reported to have a beneficial affect on
      postinfarction cardiac remodeling and dysfunction when administered before the
      onset of or at the acute stage of myocardial infarction (MI), its effect on
      established heart failure is unknown. We show here that subcutaneous
      administration of G-CSF greatly improves the function of murine hearts failing
      due to a large, healed MI. G-CSF changed the geometry of the infarct scar from
      elongated and thin to short and thick, induced hypertrophy among surviving
      cardiomyocytes, and reduced myocardial fibrosis. Expression of G-CSF receptor was
      confirmed in failing hearts and was upregulated by G-CSF treatment. G-CSF
      treatment also led to activation of signal transducer and activator of
      transcription-3 and induction of GATA-4 and various sarcomeric proteins such as
      myosin heavy chain, troponin I and desmin. Expression of metalloproteinase-2 and 
      9 was also increased in G-CSF-treated hearts, while that of tumor necrosis factor
      alpha, angiotensin II type 1 receptor (AT1) and transforming growth factor-beta1
      was reduced. Although activation of Akt was noted in G-CSF-treated hearts, vessel
      density was unchanged, and apoptosis was too rare to exert a meaningful effect.
      No bone marrow-derived cardiomyocytes or vascular cells were detected in the
      failing hearts of green fluorescent protein chimeric mice. Finally, beneficial
      effects of G-CSF on cardiac function were found persisting long after
      discontinuing the treatment (2 weeks). Collectively, these findings suggest G-CSF
      administration could be an effective approach to treating chronic heart failure
      following a large MI.

PMID- 16304580
TI  - Metabolic changes in malnutrition.
AB  - This paper is concerned with malnutrition caused by inadequate intake of all the
      major nutrients rather than deficiency diseases relating to a single
      micronutrient. Three common situations are recognised: young children in third
      world countries with protein-energy malnutrition; adults in the same countries
      who are chronically adapted to subsisting on marginally inadequate diets; and
      patients who become malnourished as a result of chronic diseases. In all these
      situations infectious diseases are often also present, and this complicates the
      interpretation of biochemical and physiological observations. The metabolic
      response to starvation is primarily concerned with maintaining a supply of water
      soluble substrates to supply energy to the brain. Thus there is an initial rise
      in metabolic rate, reflecting gluconeogenic activity. As fasting progresses,
      gluconeogenesis is suppressed to minimise muscle protein breakdown and ketones
      become the main fuel for the brain. With chronic underfeeding the basal metabolic
      rate per cell appears to fall, but the mechanistic basis for this is not clear.
      The main adaptation to chronic energy deficiency is slow growth and low adult
      body size, although the reduction in energy requirement achieved by this is
      partially offset by the preservation of the more metabolically active organs at
      the expense of muscle, which has a lower metabolic rate. The interaction between
      malnutrition and the metabolic response to trauma has been studied using an
      animal model. The rise in energy expenditure and urinary nitrogen excretion
      following surgery were significantly attenuated in malnourished rats, suggesting
      that malnutrition impairs the ability of the body to mobilise substrates to
      support inflammatory and reparative processes. However, the healing process in
      wounded muscle remained unimpaired in malnutrition, suggesting that this process
      has a high biological priority.

PMID- 16304581
TI  - Management of blinding disease: loss of immunity and superinfection.
AB  - Globally the most important loss of immunity currently occurs with HIV disease.
      The effects of HIV on the eye, since the advent of highly active antiretroviral
      therapy, have been less in countries where such treatment is available but even
      in such situations ophthalmic zoster can occur at higher CD4 cell counts and can
      still cause problems. Other opportunistic infections such as CMV retinitis tend
      to occur at lower CD4 cell counts. However, globally treatment is not universally
      available in resource poor countries where it is most needed. A major impact of
      HIV in such situations is on premature mortality affecting the health care and
      education workforce, which indirectly has an impact on blinding disease. In
      addition, loss of family income due to illness or death of parents can affect
      nutritional status of remaining family members especially children as well as the
      direct effect of opportunistic infections in the eyes of those infected with HIV.

PMID- 16304582
TI  - How should blindness in children be managed?
AB  - BACKGROUND: In all, 1.4 million children are estimated to be blind worldwide and
      only 6.5% of these are thought to come from the more affluent countries. The
      focus of this paper is therefore the developing world and Africa in particular,
      where evidence suggests that congenital cataract is becoming the leading cause of
      childhood blindness. METHODS: A review of the literature on management of
      congenital cataract was combined with original data from the author's experience
      in east Africa. CONCLUSIONS: Health service structure, surgical technique, health
      education, and community screening to promote early referral, good surgical
      follow-up, and training of multidisciplinary teams based at specialist children's
      eye centres are all essential components for effective strategies to control
      childhood blindness due to congenital cataract.

PMID- 16304583
TI  - The 'ideal' management of retinopathy of prematurity.
AB  - AIM: Retinopathy of prematurity continues to be a serious, but largely
      preventable cause of blindness and its detection and treatment is of increasing
      importance as survival rates of premature babies increase. This is particularly
      important in Medium Human Development Countries where the guidelines for
      detection used in the US or UK may not be appropriate. METHOD: This report
      addresses identification of infants at risk for retinopathy of prematurity,
      detection, and treatment of serious disease, and what to do when treatment fails.
      RESULTS AND CONCLUSIONS: Retinopathy of prematurity occurs almost exclusively in
      small premature babies, but the demographic characteristics of these babies vary
      depending on where they are born. Detection of serious retinopathy requires
      carefully timed examinations and the treatment criteria will continue to evolve
      as new therapies are developed. Timely detection and treatment of serious
      retinopathy of prematurity minimizes the likelihood of blindness, but it is not
      always successful.

PMID- 16304584
TI  - Public-private partnerships in blindness prevention: reaching beyond the eye.
AB  - The control of river blindness (onchocerciasis) has been one of the major public
      health achievements of recent decades. Initially, vector control was used to stop
      transmission of the parasite Onchocerca volvulus by blackflies (Simulium) but the
      introduction of ivermectin (Mectizan) as a means of morbidity control enabled new
      strategies of distribution to be developed based on community directed treatment.
      The donation of Mectizan by Merck & Co. Inc. for onchocerciasis control in 1987
      'as long as needed' was a public health landmark to be followed by a donation
      from GlaxoSmithKline of albendazole in 1997 for lymphatic filariasis to which
      Merck also responded by agreeing to extend their donation to include the
      coadministration of Mectizan and albendazole. Both the drugs, however, have wider
      impacts than those specific to filarial parasites and are effective against a
      range of intestinal parasites, whilst ivermectin has an important effect on
      ectoparasites. The wider benefits of the annual public health intervention
      collateral benefits--therefore include deworming, improved nutritional status,
      increased growth, improved school performance and attendance, and improved
      haemoglobin status as a result of the impact of albendazole on hookworm, a major
      cause of anaemia. More recently, studies suggest that worm-free children have a
      significantly reduced frequency of malaria specific episodes of fever and Ascaris
      infected children have a two-fold higher frequency of cerebral or severe malaria
      than those without Ascaris. These findings suggest that programmes based on
      annual interventions to control river blindness and lymphatic filariasis can
      contribute disproportionately more to a range of public health problems than has
      been hitherto recognized, thereby assisting in attaining the millennium
      development goal targets.

PMID- 16304585
TI  - Ivermectin and onchocerciasis: is it all solved?
AB  - The donation of ivermectin by Merck and Co. Inc. has led to one of the most
      effective private-public partnerships controlling a disease of major public
      health importance particularly in Africa. The up scaling of ivermectin
      distribution during the last 15 years has been remarkable with almost 40 million
      people treated in 2003, many already on their regular annual dose. The tools that
      have been developed particularly by the APOC programme have been instrumental in
      this increase. However, ivermectin is a microfilaricide and does not kill the
      adult worms. Distribution will be needed for at least 25 years and latest
      estimates indicate that 90 million people need annual treatment if onchocerciasis
      is to be eliminated as a public health problem. In spite of this incredible
      progress it is difficult to see how the programme will be sustained, especially
      after the closure of APOC in 2010. A macrofilaricide destroying adult worms and
      safe for mass distribution would solve the problem of onchocerciasis.

PMID- 16304586
TI  - Can blinding trachoma be eliminated by 20/20?
AB  - Trachoma is the leading cause of preventable blindness in the world today. Long
      ago eliminated in North America and Europe, the disease is almost unknown, and
      indeed forgotten, in the West. Nevertheless, it continues to wreak havoc in the
      poorest parts of Africa, Asia, and other areas throughout the world. The World
      Health Organization (WHO) estimates that there are currently 7.6 million people
      who are visually impaired due to trachoma, and 84 million people with active
      infections. In 1998, WHO passed a resolution calling for member states to take
      action to eliminate blinding trachoma by the year 2020. The scale of what must be
      accomplished in order to reach this goal is daunting. However, the work of the
      International Trachoma Initiative together with national governments as well as
      other organizations in applying the WHO-recommended SAFE strategy for trachoma
      control has produced critical successes in challenging settings. This paper gives
      a brief history and description of trachoma, explains treatment options and the
      SAFE strategy, and discusses successes from two trachoma control programmes as
      examples of how to move forward in eliminating this devastating disease.

PMID- 16304587
TI  - External factors in the development of cataract.
AB  - AIMS: To provide an update on the risk factors for cataract development. METHODS:
      Review of the literature. RESULTS: Age and heredity are the most important risk
      factors associated with the different types of cataract. While the hereditary
      component is self-explanatory, increasing age serves as a surrogate for a number
      of potential external risk factors, the effect of which is cumulative.
      Identification of the risk factors that have a causal effect on cataract
      development may provide means for cataract prevention. There are only a few risk
      factors that satisfy the criteria for causal effect: smoking, which results in
      the increased risk of nuclear cataract, excessive UV-B exposure and diabetes that
      increase the risk of cortical cataract, and steroidal treatment, diabetes and
      ionising radiation that lead to the formation of posterior subcapsular opacity.
      The effect of medications on cataract development requires further study, since
      the effect of the diseases should be distinguished from that of treatment. 'Stop
      Smoking' and 'UV-B protection' campaigns are gaining momentum as preventative
      measures, while the attempts to actively prevent cataract with antioxidants have
      not been successful. Cataract research has been facilitated lately by
      improvements of precision and standardisation in measuring lens opacities.
      However, measurement precision on its own cannot give us a solution to this
      problem. CONCLUSION: The major studies repeatedly measure the exposure to the
      traditional health hazards, while the missing parts in the equation are those
      risk factors that we do not know about and therefore do not measure. New
      approaches and new hypotheses are needed.

PMID- 16304588
TI  - High-volume surgery in developing countries.
AB  - BACKGROUND: Cataract remains the world's leading cause of blindness. In the
      developing world, many eye clinics provide cataract surgery for only a small
      proportion of those in need. This is partly because of low demand-caused by
      barriers related to awareness, bad services, cost, and distance--and partly
      because of deficiencies in the supply of services. This article reviews
      innovations in cataract surgery in poor countries that are intended to reverse
      this trend. CONCLUSIONS: Increasing the number of operations, through close
      involvement with the community, and improved surgical outcomes, enables the cost
      of surgery to be reduced, leading to further growth in volume. Recent
      innovations, such as low-cost intraocular lenses, and small-incision
      extracapsular cataract extraction, have contributed to improving the results of
      surgery without increasing the costs. Effective management enables the delivery
      of increasing the numbers of operations, while at the same time improving
      outcomes and controlling costs.

PMID- 16304589
TI  - Independent sector treatment centres (ISTCS): early experience from an
      ophthalmology perspective.
AB  - In 2001, the NHS plan concluded that there was a significant lack of capacity
      within current NHS structures to deliver adequate volumes of cataract surgery for
      England and Wales. The initial central 'solution' for this was to invite in
      overseas surgical teams to existing NHS centres for short-term surgical
      initiatives. However, with the advent of the Waiting, Booking and Choice
      Strategy, a target was set for treatment centers (TCs) to be carrying out an
      additional 250 000 inpatient/day-case episodes, across all specialties, by 2005.
      This paper outlines how these Ophthalmology TCs were commissioned, and some of
      the policy and medical agendas that surrounded their evolution. The concept of
      'take or pay' contracts, which placed the onus on local Primary Care Trust
      organisations to provide the promised number of suitable cataract patients for
      the TCs, and the 'additionality' of medical and nursing staff are discussed. In
      September 2003, Netcare was awarded the contract to carry out 41 600 cataract
      procedures over a 5-year period in a mixture of mobile and fixed site units.
      Netcare's proposed patient care pathways are examined, as is the reality of its
      interaction with local Ophthalmology Departments and the response of the Royal
      College of Ophthalmologists to its standards of patient care. Although Netcare
      TCs may have contributed to reduced waiting times for cataract surgery in some
      districts, the quality of care provided by the Netcare TCs has yet to be
      established. There are ongoing concerns about both the continuity of care and the
      management of postoperative complications, as well as the economics of
      neighbouring NHS units.

PMID- 16304590
TI  - Prevention of blindness in leprosy and the role of the Vision 2020 Programme.
AB  - Leprosy control programmes are highly successful. As a result, leprosy control
      will be more and more integrated into the general health services. The existing
      vertical, specialized control programmes will be dismantled. Eye complications in
      leprosy have decreased. This is a result of earlier diagnosis and highly
      effective multidrug treatment (MDT) of leprosy, combined with timely treatment of
      secondary nerve damage by steroids. Most ocular morbidity is now found among
      elderly and disabled leprosy patients who were diagnosed before effective MDT
      treatment became available. Many of these patients live in leprosy settlements.
      Age-related cataract has become the leading cause of blindness in leprosy. The
      second cause of blindness is corneal opacification, mainly as a result of
      neglected exposure keratitis and corneal anaesthesia. The miotic pupils in late
      multibacillary leprosy, in combination with small central lens opacities, may
      also lead to blindness. The Vision 2020 Initiative prioritises cataract surgery.
      Leprosy patients should be actively included. Disabled leprosy patients can also
      benefit from screening programmes for refractive errors and the provision of
      spectacles and low vision aids. Determining the most feasible surgical methods
      for lagophthalmos surgery remains a challenge. For all health and eye care staff,
      training in leprosy and its eye complications is needed, as well as a change in
      attitude towards leprosy patients. Staff must be prepared to welcome them in the
      general health services.

PMID- 16304591
TI  - The value of corneal transplantation in reducing blindness.
AB  - PURPOSE: To analyse the role of keratoplasty in reducing world blindness due to
      corneal diseases. METHODS: Review of published literature. We collected and
      analysed articles published in the English language literature related to the
      prevalence and causes of blindness in different parts of the world, causes of
      corneal blindness, and outcome of corneal transplantation for various corneal
      diseases. RESULTS: A total of 80% of the world's blind live in developing
      countries. Retinal diseases are the most important causes of blindness (40-54%)
      in established economy nations while cataract (44-60%) and corneal diseases (8
      25%) are the most common causes of blindness in countries with less developed
      economies. Keratitis during childhood, trauma, and keratitis during adulthood
      resulting in a vascularized corneal scar and adherent leucoma are the most
      frequent causes of corneal blindness in developing countries. Corneal diseases
      are responsible for 20% of childhood blindness. Nearly 80% of all corneal
      blindness is avoidable. The outcome of keratoplasty for vascularized corneal scar
      and adherent leucoma is unsatisfactory, necessitating repeat surgery in a high
      proportion of these cases. Other barriers for keratoplasty in these nations are
      suboptimal eye banking, lack of trained human resources, and infrastructure.
      CONCLUSIONS: Since the developing world carries most of the load of corneal
      blindness and the major causes of corneal blindness are corneal scar and active
      keratitis, development of corneal transplantation services need a comprehensive
      approach encompassing medical standards in eye banking, training of cornea
      specialists and eye banking personnel and exposure of ophthalmologists to care of
      corneal transplants for better follow-up care. However, concerted efforts should
      be made to develop and implement prevention strategies since most corneal
      blindness is preventable.

PMID- 16304592
TI  - Progressive changes in diabetics and their management.
AB  - The prevalence of diabetic retinopathy is increasing worldwide due to an
      increasing number, and prolonged survival, of diabetic patients. Many effective
      treatments for different types and stages of retinopathy exist. However, there is
      patchy delivery of care, inconsistent screening, and unresolved questions about
      several management questions. This article discusses the current state of
      knowledge about therapeutics in diabetic retinopathy, and highlights areas where
      further studies and evidence base is required.

PMID- 16304593
TI  - Can we prevent angle-closure glaucoma?
AB  - PURPOSE: Glaucoma is the second cause, after cataract, of world blindness.
      Approximately half is thought to be primary angle-closure glaucoma (ACG). This
      review asks whether ACG can be prevented on a population basis. METHODS AND
      POPULATIONS: Review of published information from the Inuit of Greenland, Canada
      and Alaska, and descriptions of recent studies in Asian populations in Mongolia,
      China and South-East Asia. RESULTS: The Greenland Inuit have the shallowest
      anterior chamber depths (ACDs) so far recorded. The proportion of blindness due
      to ACG was reduced from 64% to 9% over 37 years by systematic optical measurement
      of central ACD and the van Herick test in the older Inuit, followed by gonioscopy
      and prophylactic iridectomy or laser iridotomy when indicated. In Mongolia,
      ultrasound measurement of central ACD had good sensitivity and specificity as a
      screening test. A randomized controlled trial of screening and prophylactic laser
      is being completed. In China and South-East Asia, the mechanism of angle closure
      appears to be more varied and complex and its detection may require more
      elaborate imaging. CONCLUSIONS: The mechanism of angle closure and potential for
      prevention by screening are likely to have to be determined specifically for each
      population at risk.

PMID- 16304594
TI  - What is practical in glaucoma management?
AB  - This article addresses some important issues in the detection and management of
      glaucoma using examples from the developing world, particularly drawing on
      experiences and research in sub-Saharan Africa.

PMID- 16304595
TI  - The impact of Vision 2020 on global blindness.
AB  - INTRODUCTION: Recent data suggest that there are 37 million blind people and 124
      million with low vision, excluding those with uncorrected refractive errors. The
      main causes of global blindness are cataract, glaucoma, corneal scarring (from a
      variety of causes), age-related macular degeneration, and diabetic retinopathy.
      CONCLUSION: It would appear that the global Vision 2020 initiative is having an
      impact to reduce avoidable blindness particularly from ocular infections, but
      more needs to be done to address cataract, glaucoma, and diabetic retinopathy.

PMID- 16304596
TI  - Metagenomics: DNA sequencing of environmental samples.
AB  - Although genomics has classically focused on pure, easy-to-obtain samples, such
      as microbes that grow readily in culture or large animals and plants, these
      organisms represent only a fraction of the living or once-living organisms of
      interest. Many species are difficult to study in isolation because they fail to
      grow in laboratory culture, depend on other organisms for critical processes, or
      have become extinct. Methods that are based on DNA sequencing circumvent these
      obstacles, as DNA can be isolated directly from living or dead cells in various
      contexts. Such methods have led to the emergence of a new field, which is
      referred to as metagenomics.

PMID- 16304597
TI  - The organization and inheritance of the mitochondrial genome.
AB  - Mitochondrial DNA (mtDNA) encodes essential components of the cellular energy
      producing apparatus, and lesions in mtDNA and mitochondrial dysfunction
      contribute to numerous human diseases. Understanding mtDNA organization and
      inheritance is therefore an important goal. Recent studies have revealed that
      mitochondria use diverse metabolic enzymes to organize and protect mtDNA, drive
      the segregation of the organellar genome, and couple the inheritance of mtDNA
      with cellular metabolism. In addition, components of a membrane-associated mtDNA
      segregation apparatus that might link mtDNA transmission to mitochondrial
      movements are beginning to be identified. These findings provide new insights
      into the mechanisms of mtDNA maintenance and inheritance.

PMID- 16304598
TI  - Building the mammalian heart from two sources of myocardial cells.
AB  - Cardiogenesis is an exquisitely sensitive process. Any perturbation in the cells
      that contribute to the building of the heart leads to cardiac malformations,
      which frequently result in the death of the embryo. Previously, the myocardium
      was thought to be derived from a single source of cells. However, the recent
      identification of a second source of myocardial cells that make an important
      contribution to the cardiac chambers has modified the classical view of heart
      formation. It also has an important influence on the interpretation of mutant
      phenotypes in the mouse, with consequences for the classification and prognosis
      of human congenital heart defects.

PMID- 16304599
TI  - The advantages and disadvantages of being polyploid.
AB  - Polyploids - organisms that have multiple sets of chromosomes - are common in
      certain plant and animal taxa, and can be surprisingly stable. The evidence that
      has emerged from genome analyses also indicates that many other eukaryotic
      genomes have a polyploid ancestry, suggesting that both humans and most other
      eukaryotes have either benefited from or endured polyploidy. Studies of
      polyploids soon after their formation have revealed genetic and epigenetic
      interactions between redundant genes. These interactions can be related to the
      phenotypes and evolutionary fates of polyploids. Here, I consider the advantages
      and challenges of polyploidy, and its evolutionary potential.

PMID- 16304600
TI  - Genotyping errors: causes, consequences and solutions.
AB  - Although genotyping errors affect most data and can markedly influence the
      biological conclusions of a study, they are too often neglected. Errors have
      various causes, but their occurrence and effect can be limited by considering
      these causes in the production and analysis of the data. Procedures that have
      been developed for dealing with errors in linkage studies, forensic analyses and
      non-invasive genotyping should be applied more broadly to any genetic study. We
      propose a protocol for estimating error rates and recommend that these measures
      be systemically reported to attest the reliability of published genotyping
      studies.

PMID- 16304601
TI  - Programmed and altruistic ageing.
AB  - Ageing is widely believed to be a non-adaptive process that results from a
      decline in the force of natural selection. However, recent studies in
      Saccharomyces cerevisiae are consistent with the existence of a programme of
      altruistic ageing and death. We suggest that the similarities between the
      molecular pathways that regulate ageing in yeast, worms, flies and mice, together
      with evidence that is consistent with programmed death in salmon and other
      organisms, raise the possibility that programmed ageing or death can also occur
      in higher eukaryotes.

PMID- 16304603
TI  - Using mating designs to uncover QTL and the genetic architecture of complex
      traits.
AB  - Analysis of quantitative trait loci (QTL) affecting complex traits is often
      pursued in single-cross experiments. For most purposes, including breeding, some
      assessment is desired of the generalizability of the QTL findings and of the
      overall genetic architecture of the trait. Single-cross experiments provide a
      poor basis for these purposes, as comparison across experiments is hampered by
      segregation of different allelic combinations among different parents and by
      context-dependent effects of QTL. To overcome this problem, we combined the
      benefits of QTL analysis (to identify genomic regions affecting trait variation)
      and classic diallel analysis (to obtain insight into the general inheritance of
      the trait) by analyzing multiple mapping families that are connected via shared
      parents. We first provide a theoretical derivation of main (general combining
      ability (GCA)) and interaction (specific combining ability (SCA)) effects on F(2)
      family means relative to variance components in a randomly mating reference
      population. Then, using computer simulations to generate F(2) families derived
      from 10 inbred parents in different partial-diallel designs, we show that QTL can
      be detected and that the residual among-family variance can be analyzed. Standard
      diallel analysis methods are applied in order to reveal the presence and mode of
      action (in terms of GCA and SCA) of undetected polygenes. Given a fixed
      experiment size (total number of individuals), we demonstrate that QTL detection
      and estimation of the genetic architecture of polygenic effects are competing
      goals, which should be explicitly accounted for in the experimental design. Our
      approach provides a general strategy for exploring the genetic architecture, as
      well as the QTL underlying variation in quantitative traits.

PMID- 16304602
TI  - PM source apportionment and health effects: 2. An investigation of intermethod
      variability in associations between source-apportioned fine particle mass and
      daily mortality in Washington, DC.
AB  - Source apportionment may be useful in epidemiological investigation of PM health
      effects, but variations and options in these methods leave uncertainties. An EPA
      sponsored workshop investigated source apportionment and health effects analyses
      by examining the associations between daily mortality and the investigators'
      estimated source-apportioned PM(2.5) for Washington, DC for 1988-1997. A Poisson
      Generalized Linear Model (GLM) was used to estimate source-specific relative
      risks at lags 0-4 days for total non-accidental, cardiovascular, and
      cardiorespiratory mortality adjusting for weather, seasonal/temporal trends, and
      day-of-week. Source-related effect estimates and their lagged association
      patterns were similar across investigators/methods. The varying lag structure of
      associations across source types, combined with the Wednesday/Saturday sampling
      frequency made it difficult to compare the source-specific effect sizes in a
      simple manner. The largest (and most significant) percent excess deaths per 5
      95(th) percentile increment of apportioned PM(2.5) for total mortality was for
      secondary sulfate (variance-weighted mean percent excess mortality=6.7% (95% CI:
      1.7, 11.7)), but with a peculiar lag structure (lag 3 day). Primary coal-related
      PM(2.5) (only three teams) was similarly significantly associated with total
      mortality with the same 3-day lag as sulfate. Risk estimates for traffic-related
      PM(2.5), while significant in some cases, were more variable. Soil-related PM
      showed smaller effect size estimates, but they were more consistently positive at
      multiple lags. The cardiovascular and cardiorespiratory mortality associations
      were generally similar to those for total mortality. Alternative weather models
      generally gave similar patterns, but sometimes affected the lag structure (e.g.,
      for sulfate). Overall, the variations in relative risks across
      investigators/methods were found to be much smaller than those across estimated
      source types or across lag days for these data. This consistency suggests the
      robustness of the source apportionment in health effects analyses, but remaining
      issues, including accuracy of source apportionment and source-specific
      sensitivity to weather models, need to be investigated.

PMID- 16304604
TI  - Genetic load in subdivided populations: interactions between the migration rate,
      the size and the number of subpopulations.
AB  - We assess the relative importance of migration rate, size and number of
      subpopulations on the genetic load of subdivided populations. Using diffusion
      approximations, we show that in most cases subdivision has detrimental effects on
      fitness. Moreover, our results suggest that fitness increases with subpopulation
      size, so that for the same total population size, genetic load is relatively
      lower when there are a small number of large subpopulations. Using elasticity
      analysis, we show that the size of the subpopulations appears to be the parameter
      that most strongly determines genetic load. interconnecting subpopulations via
      migration would also be of importance for population fitness when subpopulations
      are small and gene flow is low. Interestingly, the number of subpopulations has
      minor influence on genetic load except for the case of both very slightly
      deleterious mutations and small subpopulations. Elasticities decrease as the
      magnitude of deleterious effects increases. In other words, population structure
      does not matter for very deleterious alleles, but strongly affects fitness for
      slightly deleterious alleles.

PMID- 16304605
TI  - Additive genetic variation of transcriptional regulation: metallothionein
      expression in the soil insect Orchesella cincta.
AB  - Field-selected metal tolerance in Orchesella cincta is correlated with
      overexpression of the single copy cadmium (Cd) inducible metallothionein (mt).
      Previously, we have demonstrated large phenotypic variation in mt gene
      expression, and a higher frequency of high-expression phenotypes in a tolerant
      population. Here, we describe midparent-offspring regression analysis of mt gene
      expression in a laboratory culture originating from a noncontaminated natural
      population. Families were either not exposed (n=47) or exposed to 0.5 micromol Cd
      per gram dry food (n=46). Mean mt gene expressions normalized to 28S rRNA and
      beta-actin RNA were generated using real-time RT-PCR applied to parents and
      offspring RNA and subjected to regression analysis. A significant heritability
      (h2) for mt gene expression was estimated between 0.36 (beta-actin normalized)
      and 0.46 (28S normalized) in Cd exposed families. Nontreated families did not
      yield a significant h2 value. Restriction Fragment Length Polymorphism analysis
      of the metallothionein promoter sequence revealed eight promoter alleles that
      show structural variation. Three alleles show increased frequencies in families
      with high mt expression. Another gene, croquemort (isolated from a differential
      screening for 1 micromole Cd treatment) showed no h2 of gene expression in
      response to 0.5 micromol Cd. This gene codes for a receptor-protein involved in
      recognition of apoptotic cells and may participate in the general stress
      response. The present data suggest that evolution of metal tolerance in O. cincta
      can occur in the field by selection for high mt expression due to structural
      changes in mt cis-regulation.

PMID- 16304606
TI  - Effect of gene flow on spatial genetic structure in the riparian canopy tree
      Cercidiphyllum japonicum revealed by microsatellite analysis.
AB  - Few studies have analyzed pollen and seed movements at local scale, and genetic
      differentiation among populations covering the geographic distribution range of a
      species. We carried out such a study on Cercidiphyllum japonicum; a dioecious
      broad-leaved tree of cool-temperate riparian forest in Japan. We made direct
      measurement of pollen and seed movements in a site, genetic structure at the
      local scale, and genetic differentiation between populations covering the
      Japanese Archipelago. Parentage analysis of seedlings within a 20-ha study site
      indicated that at least 28.8% of seedlings were fertilized by pollen from trees
      outside the study site. The average pollination distance within the study site
      was 129 m, with a maximum of 666 m. The genotypes of 30% of seedlings were
      incompatible with those of the nearest female tree, and the maximum seed
      dispersal distance within the study site was over 300 m. Thus, long-distance gene
      dispersal is common in this species. The correlation between genetic relatedness
      and spatial distance among adult trees within the population was not significant,
      indicating an absence of fine-scale genetic structure perhaps caused by high
      levels of pollen flow and overlapping seed shadows. Six populations sampled
      throughout the distribution of C. japonicum in Japan showed significant isolation
      by-distance but low levels of genetic differentiation (F(ST) = 0.043), also
      indicating long-distance gene flow in C. japonicum. Long-distance gene flow had a
      strong influence on the genetic structure at different spatial scales, and
      contributes to the maintenance of genetic diversity in C. japonicum.

PMID- 16304607
TI  - Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47
      resistance GTPases.
AB  - The p47 GTPases are essential for interferon-gamma-induced cell-autonomous
      immunity against the protozoan parasite, Toxoplasma gondii, in mice, but the
      mechanism of resistance is poorly understood. We show that the p47 GTPases,
      including IIGP1, accumulate at vacuoles containing T. gondii. The accumulation is
      GTP-dependent and requires live parasites. Vacuolar IIGP1 accumulations undergo a
      maturation-like process accompanied by vesiculation of the parasitophorous
      vacuole membrane. This culminates in disruption of the parasitophorous vacuole
      and finally of the parasite itself. Over-expression of IIGP1 leads to accelerated
      vacuolar disruption whereas a dominant negative form of IIGP1 interferes with
      interferon-gamma-mediated killing of intracellular parasites. Targeted deletion
      of the IIGP1 gene results in partial loss of the IFN-gamma-mediated T. gondii
      growth restriction in mouse astrocytes.

PMID- 16304609
TI  - Mechanisms of assembly and cellular interactions for the bacterial genotoxin CDT.
AB  - Many bacterial pathogens that cause different illnesses employ the cytolethal
      distending toxin (CDT) to induce host cell DNA damage, leading to cell cycle
      arrest or apoptosis. CDT is a tripartite holotoxin that consists of a DNase I
      family nuclease (CdtB) bound to two ricin-like lectin domains (CdtA and CdtC).
      Through the use of structure-based mutagenesis, biochemical and cellular toxicity
      assays, we have examined several key structural elements of the CdtA and CdtC
      subunits for their importance to toxin assembly, cell surface binding, and
      activity. CdtA and CdtC possess N- and C-terminal nonglobular polypeptides that
      extensively interact with each other and CdtB, and we have determined the
      contribution of each to toxin stability and activity. We have also functionally
      characterized two key binding elements of the holotoxin revealed from its crystal
      structure. One is an aromatic cluster in CdtA, and the other is a long and deep
      groove that is formed at the interface of CdtA and CdtC. We demonstrate that
      mutations of the aromatic patch or groove residues impair toxin binding to HeLa
      cells and that cell surface binding is tightly correlated with intoxication of
      cultured cells. These results establish several structure-based hypotheses for
      the assembly and function of this toxin family.

PMID- 16304608
TI  - Plasmodium falciparum variant surface antigen expression patterns during malaria.
AB  - The variant surface antigens expressed on Plasmodium falciparum-infected
      erythrocytes are potentially important targets of immunity to malaria and are
      encoded, at least in part, by a family of var genes, about 60 of which are
      present within every parasite genome. Here we use semi-conserved regions within
      short var gene sequence "tags" to make direct comparisons of var gene expression
      in 12 clinical parasite isolates from Kenyan children. A total of 1,746 var
      clones were sequenced from genomic and cDNA and assigned to one of six sequence
      groups using specific sequence features. The results show the following. (1) The
      relative numbers of genomic clones falling in each of the sequence groups was
      similar between parasite isolates and corresponded well with the numbers of genes
      found in the genome of a single, fully sequenced parasite isolate. In contrast,
      the relative numbers of cDNA clones falling in each group varied considerably
      between isolates. (2) Expression of sequences belonging to a relatively conserved
      group was negatively associated with the repertoire of variant surface antigen
      antibodies carried by the infected child at the time of disease, whereas
      expression of sequences belonging to another group was associated with the
      parasite "rosetting" phenotype, a well established virulence determinant. Our
      results suggest that information on the state of the host-parasite relationship
      in vivo can be provided by measurements of the differential expression of
      different var groups, and need only be defined by short stretches of sequence
      data.

PMID- 16304611
TI  - Salmonella pathogenicity island 2 is expressed prior to penetrating the
      intestine.
AB  - Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen
      that causes disease in mice that resembles human typhoid. Typhoid pathogenesis
      consists of distinct phases in the intestine and a subsequent systemic phase in
      which bacteria replicate in macrophages of the liver and spleen. The type III
      secretion system encoded by Salmonella pathogenicity island 2 (SPI-2) is a major
      virulence factor contributing to the systemic phase of typhoid pathogenesis.
      Understanding how pathogens regulate virulence mechanisms in response to the
      environment, including different host tissues, is key to our understanding of
      pathogenesis. A recombinase-based in vivo expression technology system was
      developed to assess SPI-2 expression during murine typhoid. SPI-2 expression was
      detectable at very early times in bacteria that were resident in the lumen of the
      ileum and was independent of active bacterial invasion of the epithelium. We also
      provide direct evidence for the regulation of SPI-2 by the Salmonella
      transcription factors ompR and ssrB in vivo. Together these results demonstrate
      that SPI-2 expression precedes penetration of the intestinal epithelium. This
      induction of expression precedes any documented SPI-2-dependent phases of typhoid
      and may be involved in preparing Salmonella to successfully resist the
      antimicrobial environment encountered within macrophages.

PMID- 16304612
TI  - Developmental interaction between suboptimal instars of Spodoptera littoralis
      (Lepidoptera:Noctuidae) and its parasitoid Microplitis rufiventris
      (Hymenoptera:Braconidae).
AB  - Relative effects of parasitism by Microplitis rufiventris on the development of
      the third instar Spodoptera littoralis (preferable, optimal host) with the
      development of penultimate (5th) and last (6th) instars (suboptimal hosts) were
      investigated. Newly molted 6th instar hosts were more acceptable for
      parasitization by the wasp female than older hosts. In singly parasitized 3rd
      instar hosts, 82.0 +/- 3.9% of the parasitoid eggs developed to full-grown instar
      wasp larvae. However, parasitoid eggs deposited singly in 73.9 +/- 3.3% of 5th
      and 100% of 6th instar hosts failed to develop. Superparasitization in the 3rd
      instar hosts reduced the production of pseudoparasitized larvae and, conversely,
      all parasitized hosts yielded viable parasitoid offspring. In suboptimal hosts,
      the development interaction between the parasitoid and its host larvae was highly
      influenced by the age of hosts at parasitism, load of deposited eggs, and other
      parasitoid factors. The latter factors, e.g., mainly calyx fluid particles, might
      be involved in establishing parasitoid eggs in the suboptimal hosts. In the last
      two host instars, superparasitization significantly increased the number of
      parasitoid larvae successfully reaching their final instar. Variation in host
      quality, e.g., physiological status, might be attributed, in part, to the partial
      breakdown of the solitary habit observed in the earlier instars. More parasitoid
      eggs developed to mature parasitoid larvae in hosts superparasitized as 6th
      instar than parasitoid eggs laid in 5th instar hosts. Superparasitization
      significantly lengthened the developmental period of 5th and 6th host instars and
      inhibited their development to the pupal stage. Studying parasitoid development
      in suboptimal instars of its habitual host provided physiological insight, as
      shown here. The results may have implication for biological control and in vitro
      mass rearing programs with solitary parasitoids.

PMID- 16304610
TI  - Aspergillus fumigatus triggers inflammatory responses by stage-specific beta
      glucan display.
AB  - Inhalation of fungal spores (conidia) occurs commonly and, in specific
      circumstances, can result in invasive disease. We investigated the murine
      inflammatory response to conidia of Aspergillus fumigatus, the most common
      invasive mold in immunocompromised hosts. In contrast to dormant spores,
      germinating conidia induce neutrophil recruitment to the airways and TNF
      alpha/MIP-2 secretion by alveolar macrophages. Fungal beta-glucans act as a
      trigger for the induction of these inflammatory responses through their time
      dependent exposure on the surface of germinating conidia. Dectin-1, an innate
      immune receptor that recognizes fungal beta-glucans, is recruited in vivo to
      alveolar macrophage phagosomes that have internalized conidia with exposed beta
      glucans. Antibody-mediated blockade of Dectin-1 partially inhibits TNF-alpha/MIP
      2 induction by metabolically active conidia. TLR-2- and MyD88-mediated signals
      provide an additive contribution to macrophage activation by germinating conidia.
      Selective responsiveness to germinating conidia provides the innate immune system
      with a mechanism to restrict inflammatory responses to metabolically active,
      potentially invasive fungal spores.

PMID- 16304613
TI  - Parasitic suppression of feeding in the tobacco hornworm, Manduca sexta:
      parallels with feeding depression after an immune challenge.
AB  - The parasitic wasp, Cotesia congregata, suppresses feeding in its host Manduca
      sexta. Feeding suppression in the host coincides with the emergence of the wasps
      through the host's cuticle. During wasp emergence, host hemocyte number declined,
      suggesting that the host mounts a wound/immune response against the exiting
      parasitoids and/or resulting tissue damage. Eliciting a different type of immune
      response by injecting heat-killed Serratia marcescens also resulted in a decline
      in feeding and a reduction in hemocyte number. Both the emerging wasps and the
      bacteria induced an increase in hemolymph octopamine concentration and a decrease
      in foregut peristalsis in M. sexta. The emerging parasitoids produced the largest
      changes. The source of the additional octopamine appeared to be the host in both
      cases. S. marcescens was found to contain no detectable amounts of octopamine.
      The parasitoids had insufficient octopamine to account for the amount found in
      host hemolymph and they did not secrete octopamine in vitro. One cause for the
      high concentration of octopamine in parasitized M. sexta was that octopamine was
      removed from the hemolymph approximately 23 times more slowly after the wasps
      emerged than prior to wasp emergence. The striking similarity between the effects
      of parasitoids and bacteria on M. sexta feeding, hemocyte number, hemolymph
      octopamine concentration, and foregut peristalsis supports the possibility that
      the immune/wound reaction induced by the emerging wasps could play a role in the
      suppression of host feeding. These results also support the hypothesis that M.
      sexta exhibit an immune-activated anorexia.

PMID- 16304614
TI  - Host-parasite interactions between whiteflies and their parasitoids.
AB  - There is relatively little information available concerning the physiological and
      biochemical interactions between whiteflies and their parasitoids. In this
      report, we describe interactions between aphelinid parasitoids and their
      aleyrodid hosts that we have observed in four host-parasite systems: Bemisia
      tabaci/Encarsia formosa, Trialeurodes vaporariorum/E. formosa, B.
      tabaci/Eretmocerus mundus, and T. lauri/Encarsia scapeata. In the absence of
      reported polydnavirus and teratocytes, these parasitoids probably inject and/or
      produce compounds that interfere with the host immune response and also
      manipulate host development to suit their own needs. In addition, parasitoids
      must coordinate their own development with that of their host. Although eggs are
      deposited under all four instars of B. tabaci, Eretmocerus larvae only penetrate
      4th instar B. tabaci nymphs. A pre-penetrating E. mundus first instar was capable
      of inducing permanent developmental arrest in its host, and upon penetration
      stimulated its host to produce a capsule (epidermal in origin) in which the
      parasitoid larva developed. T. vaporariorum and B. tabaci parasitized by E.
      formosa initiated adult development, and, on occasion, produced abnormal adult
      wings and eyes. In these systems, the site of parasitoid oviposition depended on
      the host species, occurring within or pressing into the ventral ganglion in T.
      vaporariorum and at various locations in B. tabaci. E. formosa's final larval
      molt is cued by the initiation of adult development in its host. In the T. lauri
      E. scapeata system, both the host whitefly and the female parasitoid diapause
      during most of the year, i.e., from June until the middle of February (T. lauri)
      or from May until the end of December (E. scapeata). It appears that the growth
      and development of the insects are directed by the appearance of new, young
      foliage on Arbutus andrachne, the host tree. When adult female parasitoids
      emerged in the spring, they laid unfertilized male-producing eggs in whiteflies
      containing a female parasitoid [autoparasitism (development of male larvae
      utilizing female parasitoid immatures for nutrition)]. Upon hatching, these male
      larvae did not diapause, but initiated development, and the adult males that
      emerged several weeks later mated with available females to produce the next
      generation of parasitoid females. Thus, the interactions that exist between
      whiteflies and their parasitoids are complex and can be quite diverse in the
      various host-parasitoid systems.

PMID- 16304615
TI  - Sugar convertibility in the parasitoid Cotesia glomerata (Hymenoptera:
      Braconidae).
AB  - Lack of suitable sugar sources for adult parasitic wasps is an important cause of
      failure in biological control programs, but the metabolic constraints of sugar
      feeding are poorly understood. Here we investigated the suitability of 11
      naturally occurring sugars as energy sources for the parasitoid Cotesia glomerata
      (L.) (Hymenoptera: Braconidae). By feeding energy-deprived individuals with given
      quantities of a 40% (w:w) sugar solution, we assessed recovery time and lifespan
      after feeding. More than 50% of the wasps recovered within 20 min, and at least
      80% within 60 min after uptake of one of the monosaccharides fructose or glucose,
      the disaccharide sucrose, or the trisaccharide melezitose. Between 40 to 80% of
      the test insects recovered within an hour after intake of maltose, raffinose,
      galactose, or mannose. Less than 25% recovered within 1 h after uptake of
      melibiose, trehalose, rhamnose, or water (control). Parasitoids obtained the
      highest lifespan benefits after intake of glucose, fructose, sucrose, or
      melezitose, indicating and confirming their convertibility as an energy source
      for C. glomerata. In contrast, no lifespan increase was found after consumption
      of rhamnose and trehalose. The differences in recovery time and lifespan are
      discussed in terms of parasitoid enzyme activity and metabolic processes.

PMID- 16304617
TI  - Are insect immune suppressors driving cellular uptake reactions?
AB  - Many insect parasitoids that deposit their eggs inside immature stages of other
      insect species inactivate the cellular host defence to protect the growing embryo
      from encapsulation. Suppression of encapsulation by polydnavirus-encoded immune
      suppressors correlates with specific alterations in hemocytes, mainly
      cytoskeletal rearrangements and actin-cytoskeleton breakdown. We have previously
      shown that the Cotesia rubecula polydnavirus gene product CrV1 causes immune
      suppression when injected into the host hemocoel. CrV1 is taken up by hemocytes
      although no receptors have been found to bind the protein. Instead CrV1 uptake
      depends on dimer formation, which is required for interacting with lipophorin,
      suggesting a CrV1-lipophorin complex internalisation by hemocytes. Since
      treatment of hemocytes with oligomeric lectins and cytochalasin D can mimic the
      effects of CrV1, we propose that some dimeric and oligomeric adhesion molecules
      are able to cross-link receptors on the cell surface and depolymerise actin by
      leverage-mediated clearance reactions in the hemolymph.

PMID- 16304618
TI  - Host refractoriness of the tobacco hornworm, Manduca sexta, to the braconid
      endoparasitoid Cotesia flavipes.
AB  - Cotesia flavipes (Hymenoptera:Braconidae) is a gregarious endoparasitoid of
      several pyralid stemborer larvae of economic significance including the sugarcane
      borer, Diatraea saccharalis. In this study, the ability of this parasitoid to
      develop in a sphingid host, Manduca sexta, was tested. First, second, third,
      fourth, and even pharate fifth instar host tobacco hornworm larvae were readily
      parasitized by the female C. flavipes parasitoids but no wasp larvae hatched from
      the eggs in this refractory host. Instead, the parasitoid eggs were invariably
      encapsulated by the host's hemocytes and, ultimately, no parasitoids emerged from
      tobacco hornworm hosts. The first stages of encapsulation were evident at 2 h
      post-parasitization of the host M. sexta larvae, when the beginning stages of
      capsule formation were seen. The developmental fate of the host larvae with
      encapsulated parasitoids was variable. Most succumbed as abnormally small fifth
      instars or as post-wandering prepupal animals, while a few developed normally to
      the pupal stage. Dissection of all the larvae or pupae with encapsulated wasp
      eggs showed evidence of hemocytic encapsulation and melanization of the C.
      flavipes eggs. This report describes the association between C. flavipes and M.
      sexta, which appears to be an excellent model system for studying the
      physiological processes accompanying wasp egg encapsulation that result in death
      of the host as well as the parasitoid. Since the parasitoid egg never hatches,
      the system offers an excellent opportunity to identify and study the effects of
      parasitoid-injected polydnavirus and venom on host physiology.

PMID- 16304619
TI  - Parasitoid wasp uses a venom cocktail injected into the brain to manipulate the
      behavior and metabolism of its cockroach prey.
AB  - Unlike other venomous predators, the parasitoid wasp Ampulex compressa
      incapacitates its prey, the cockroach Periplaneta americana, to provide a fresh
      food supply for its offspring. We first established that the wasp larval
      development, from egg laying to pupation, lasts about 8 days during which the
      cockroach must remain alive but immobile. To this end, the wasp injects a
      cocktail of neurotoxins to manipulate the behavior of the cockroach. The cocktail
      is injected directly into the head ganglia using biosensors located on the
      stinger. The head sting induces first 30 min of intense grooming followed by
      hypokinesia during which the cockroach is unable to generate an escape response.
      In addition, stung cockroaches survive longer, lose less water, and consume less
      oxygen. Dopamine contained in the venom appears to be responsible for inducing
      grooming behavior. For the hypokinesia, our hypothesis is that the injected venom
      affects neurons located in the head ganglia, which send descending tonic input to
      bioaminergic neurons. These, in turn, control the thoracic premotor circuitry for
      locomotion. We show that the activity of identified octopaminergic neurons from
      the thoracic ganglia is altered in stung animals. The alteration in the
      octopaminergic neurons' activity could be one of the mechanisms by which the
      venom modulates the escape circuit in the cockroach's central nervous system and
      metabolism in the peripheral system.

PMID- 16304620
TI  - Wolbachia and reproductive conflict in Exorista sorbillans.
AB  - Many arthropods harbour endosymbiotic bacteria of the genus Wolbachia. These
      endosymbionts are transmitted vertically from one generation to the next and are
      obligatory in several Dipterans that have been studied to date. These bacteria
      induce an array of reproductive isolation mechanisms that are implicated in pest
      management to evolutionary biology of respective hosts. The uzifly, Exorista
      sorbillans, a tachinid endoparasitoid of the silkworm, Bombyx mori L.
      (Lepidoptera: Bombycidae), causes enormous losses to the silk industry; now it is
      known that it harbours Wolbachia endobacteria. The elimination of Wolbachia by
      antibiotics interrupts embryogenesis and causes various reproductive conflicts
      such as (1) a reduction of fecundity of uninfected female, (2) cytoplasmic
      incompatibility in the uninfected females crossed with infected males, (3)
      genomic incompatibility in crosses between males and females from uninfected
      population, and (4) sex-ratio distortion in uninfected females irrespective of
      the presence of Wolbachia in males. These results suggest that the relationship
      of Wolbachia with its uzifly host is one of mutual symbiosis as it controls the
      reproductive physiology of its host.

PMID- 16304621
TI  - Predicting physical activity and outcome expectations in cancer survivors: an
      application of Self-Determination Theory.
AB  - The purpose of this study was to examine the contributions of autonomous and
      controlled motives drawn from Self-Determination Theory (SDT; Intrinsic
      Motivation and Self-determination in Human Behavior. Plenum Press: New York,
      1985; Handbook of Self-determination Research. University of Rochester Press: New
      York, 2002) towards predicting physical activity behaviours and outcome
      expectations in adult cancer survivors. Participants were cancer-survivors
      (N=220) and a non-cancer comparison cohort (N=220) who completed an adapted
      version of the Treatment Self-Regulation Questionnaire modified for physical
      activity behaviour (TSRQ-PA), an assessment of the number of minutes engaged in
      moderate-to-vigorous physical activity (MVPA) weekly, and the anticipated
      outcomes expected from regular physical activity (OE). Simultaneous multiple
      regression analyses indicated that autonomous motives was the dominant predictor
      of OEs across both cancer and non-cancer cohorts (R(2adj)=0.29-0.43), while MVPA
      was predicted by autonomous (beta's ranged from 0.21 to 0.34) and controlled
      (beta's ranged from -0.04 to -0.23) motives after controlling for demographic
      considerations. Cancer status (cancer versus no cancer) did not moderate the
      motivation-physical activity relationship. Collectively, these findings suggest
      that the distinction between autonomous and controlled motives is useful and
      compliments a growing body of evidence supporting SDT as a framework for
      understanding motivational processes in physical activity contexts with cancer
      survivors.

PMID- 16304622
TI  - Quality of life among long-term survivors of breast cancer: Different types of
      antecedents predict different classes of outcomes.
AB  - Quality of life (QOL) has many aspects, both in the short-term and in the long
      term. Different aspects of QOL may have different types of precursors:
      demographic, medical, and psychosocial. We examined this possibility in a group
      of long-term breast cancer survivors. Early-stage breast cancer patients (N =
      163) who had provided information about medical, demographic, and psychosocial
      variables during the year after surgery completed a multidimensional measure of
      QOL 5-13 years later. Initial chemotherapy and higher stage predicted greater
      financial problems and greater worry about appearance at follow-up. Being
      partnered at diagnosis predicted many psychosocial benefits at follow-up.
      Hispanic women reported greater distress and social avoidance at follow-up.
      Initial trait optimism predicted diverse aspects of better psychosocial QOL at
      follow-up, but not other aspects of QOL. Thus, different aspects of QOL at long
      term follow-up had different antecedents. Overall, psychological outcomes were
      predicted by psychosocial variables, presence of a partner at diagnosis, and
      ethnicity. Financial outcomes, in contrast, were predicted by medical variables,
      which otherwise predicted little about long-term QOL. This divergence among
      aspects of QOL should receive closer attention in future work.

PMID- 16304623
TI  - Barriers to repeat mammography: cultural perspectives of African-American, Asian,
      and Hispanic women.
AB  - Women of minority races and ethnicities have lower mammography return rates
      compared to Caucasians. To better understand barriers to mammography, we
      conducted six focus groups with 49 women of minority races and ethnicities (19
      Asian, 16 African-American, and 14 Hispanic) recruited from outpatient medical
      clinics in Boston. Eligible women had at least one prior mammogram and no
      personal history of cancer. Discussions were recorded and transcribed, and
      thematic content analyses were performed. African-Americans and Hispanics felt
      that lack of insurance was not a barrier to mammography as they were aware of
      free programs. Some African-Americans avoided mammograms because they were
      fatalistic and believed that a breast cancer diagnosis would inevitably lead to
      death. African-Americans agreed that social issues, such as drug and domestic
      abuse, made obtaining preventive health care less important. Asian participants
      agreed that mammogram return rates were poor because appointments took time away
      from work. Asian and Hispanic women identified discourteous behavior by hospital
      staff as a barrier. Cultural barriers to repeat mammography appear to vary among
      different racial groups. Interventions to improve screening among minority
      populations may be more successful if they address group-specific concerns.

PMID- 16304624
TI  - Differential connections of the perirhinal and parahippocampal cortex with the
      orbital and medial prefrontal networks in macaque monkeys.
AB  - Previous anatomical studies indicate that the orbital and medial prefrontal
      cortex (OMPFC) of monkeys is organized into an "orbital" network, which appears
      to be related to feeding and reward, and a "medial" network, related to visceral
      control and emotion. In this study, we examined the connections of the orbital
      and medial prefrontal networks with the perirhinal (areas 35 and 36) and
      parahippocampal (areas TF and TH) cortex with anterograde and retrograde axonal
      tracers. The perirhinal cortex is reciprocally connected with orbital network
      areas Iapm, Iam, Ial, 13m, 13l, 12r, and 11l. In contrast, the parahippocampal
      cortex is reciprocally connected with the medial network, especially areas around
      the corpus callosum (areas 24a/b, caudal 32, and 25), and with area 11m.
      Projections from the parahippocampal cortex also extend to areas 10m, 10o, Iai,
      and rostral area 32, as well as to dorsolateral areas 9 and 46. In addition, both
      the perirhinal and parahippocampal cortex are reciprocally connected with areas
      that are intermediate between the orbital and medial networks (areas 13a, 13b,
      and 14c) and with the supracallosal area 24a'/b'. Outside the frontal cortex, the
      perirhinal cortex and the orbital prefrontal network are both interconnected with
      the ventral part of the temporal pole (TG), area TE and the ventral bank and
      fundus of the superior temporal sulcus (STS), and the dysgranular insula. In
      contrast, the parahippocampal cortex and the medial prefrontal network are
      connected with the dorsal TG, the rostral superior temporal gyrus (STG) and
      dorsal bank of STS, and the retrosplenial cortex.

PMID- 16304625
TI  - Neuron numbers in the sensory trigeminal nuclei of the rat: A GABA- and glycine
      immunocytochemical and stereological analysis.
AB  - The volume, total neuron number, and number of GABA- and glycine-expressing
      neurons in the sensory trigeminal nuclei of the adult rat were estimated by
      stereological methods. The mean volume is 1.38+/-0.13 mm3 (mean+/-SD) for the
      principal nucleus (Vp), 1.59+/-0.06 for the n. oralis (Vo), 2.63+/-0.34 for the
      n. interpolaris (Vip), and 3.73+/-0.11 for the n. caudalis (Vc). The total neuron
      numbers are 31,900+/-2,200 (Vp), 21,100+/-3,300 (Vo), 61,600+/-8,300 (Vip), and
      159,100+/-25,300 (Vc). Immunoreactive (-ir) neurons were classified as strongly
      stained or weakly stained, depending on qualitative criteria, cross-checked by a
      densitometric analysis. GABA-ir cells are most abundant in Vc, in an increasing
      rostrocaudal gradient within the nucleus. Lower densities are found in Vip and
      Vp. The mean total number of strongly labeled GABA-ir neurons ranges between
      1,800 in Vp to 7,800 in Vip and 22,900 in Vc, and varies notably between
      subjects. Glycine-ir neurons are more numerous and display more homogeneous
      densities in all nuclei. Strongly labeled Gly-ir cells predominate in all nuclei,
      their total number ranging between 9,400 in Vp to 24,300 in Vip and 34,200 in Vc.
      A substantial fraction of immunolabeled neurons in all nuclei coexpress GABA and
      glycine. In general, all neurons strongly immunoreactive for GABA are small,
      while weakly GABA-ir cells which coexpress Gly are larger. In Vc, one-third of
      all neurons are immunoreactive: 16.6% of them are single-labeled for GABA and
      31.6% are single-labeled for glycine. The remaining 51.8% express GABA and
      glycine in different combinations, with those showing strong double labeling
      accounting for 22.6%.

PMID- 16304626
TI  - Effects of intracerebroventricular losartan on angiotensin II-mediated pressor
      responses and c-fos expression in near-term ovine fetus.
AB  - The renin-angiotensin system plays an important role in cardiovascular control.
      Intracerebroventricular (i.c.v.) angiotensin (ANG) II causes a reliable pressor
      response in the fetus at 90% gestation. To determine the roles of brain AT1 and
      AT2 receptors in this response, the effects of the central AT1 and AT2 receptor
      antagonists losartan and PD123319 were investigated in chronically prepared near
      term ovine fetuses. Losartan at 0.5 mg/kg (i.c.v.) abolished central ANG II
      induced pressor responses. High-dose losartan (5 mg/kg, i.c.v.) showed a
      potentiation of the pressor response to i.c.v. ANG II, accompanied by
      bradycardia. Associated with the pressor responses, c-fos expression in the
      cardiovascular controlling areas was significantly different between the low and
      high doses of losartan. These areas included the subfornical organ, median
      preoptic nucleus, organum vasculosum of the lamina terminalis, and
      paraventricular nuclei in the forebrain, and the tractus solitarius nuclei,
      lateral parabrachial nuclei in the hindbrain. Low-dose losartan markedly reduced
      c-fos in these areas after i.c.v. ANG II, while the high-dose losartan together
      with ANG II elicited a much stronger FOS-immunoreactivity in these areas than
      that induced by i.c.v. ANG II alone. This is a novel finding, that c-fos
      expression in the brain can be both activated and inhibited under the same
      condition. Central ANG II-induced fetal pressor responses were not altered by
      PD123319 (0.8 mg/kg). These results indicate that i.c.v. losartan at a high and a
      low dose has strikingly different effects on central ANG II-induced pressor
      responses in fetuses at late gestation, and that the AT1 mechanism plays an
      important role in fetal cardiovascular regulation.

PMID- 16304627
TI  - RC3/neurogranin is expressed in pyramidal neurons of motor and somatosensory
      cortex in normal and denervated monkeys.
AB  - RC3/neurogranin is a neuron-specific calpacitin located in the cytoplasm and,
      especially, in dendrites and dendritic spines of cortical neurons, involved in
      many aspects of excitatory transmission and long-term potentiation. We
      investigated RC3 expression in pyramidal cortical neurons and interneurons of the
      motor and somatosensory cortex of normal Macaca fascicularis by means of double
      immunofluorescence and with techniques that combine immunohistochemistry and
      radioactive in situ hybridization. We show that RC3 is expressed in virtually all
      pyramidal neurons and spiny stellate neurons of neocortical areas 4, 3b, 1, 2, 5,
      7, and SII, but not in the majority of cortical interneurons. RC3 protein and
      mRNA are tightly colocalized with the alpha subunit of CaM kinase II and the 200
      kD, nonphosphorylated neurofilament, whereas they are absent from cells
      expressing the 27-kD, vitamin D-dependent calbindin and parvalbumin. In order to
      investigate possible activity-dependent regulation of the expression of RC3, we
      compared these results with those obtained from monkeys subjected to chronic
      peripheral cutaneous denervation of the first finger. We found that the pattern
      of distribution of RC3 in motor and somatosensory cortices after nerve cut did
      not differ from normal.

PMID- 16304628
TI  - Trigeminal transition zone/rostral ventromedial medulla connections and
      facilitation of orofacial hyperalgesia after masseter inflammation in rats.
AB  - Recent studies have implicated a role for the trigeminal interpolaris/caudalis
      (Vi/Vc) transition zone in response to orofacial injury. Using combined neuronal
      tracing and Fos protein immunocytochemistry, we investigated functional
      connections between the Vi/Vc transition zone and rostral ventromedial medulla
      (RVM), a key structure in descending pain modulation. Rats were injected with a
      retrograde tracer, FluoroGold, into the RVM 7 days before injection of an
      inflammatory agent, complete Freund's adjuvant, into the masseter muscle and
      perfused at 2 hours postinflammation. A population of neurons in the ventral
      Vi/Vc overlapping with caudal ventrolateral medulla, and lamina V of the
      trigeminal subnucleus caudalis (Vc), exhibited FluoroGold/Fos double staining,
      suggesting the activation of the trigeminal-RVM pathway after inflammation. No
      double-labeled neurons were found in the dorsal Vi/Vc and laminae I-IV of Vc.
      Injection of an anterograde tracer, Phaseolus vulgaris leucoagglutinin, into the
      RVM resulted in labeling profiles overlapped with the region that showed
      FluoroGold/Fos double labeling, suggesting reciprocal connections between RVM and
      Vi/Vc. Lesions of Vc with a soma-selective neurotoxin, ibotenic acid,
      significantly reduced inflammation-induced Fos expression as well as the number
      of FluoroGold/Fos double-labeled neurons in the ventral Vi/Vc (P<0.05). Compared
      with control rats, lesions of the RVM (n=6) or Vi/Vc (n=6) with ibotenic acid led
      to the elimination or attenuation of masseter hyperalgesia/allodynia developed
      after masseter inflammation (P<0.05-0.01). The present study demonstrates
      reciprocal connections between the ventral Vi/Vc transition zone and RVM. The
      Vi/Vc-RVM pathway is activated after orofacial deep tissue injury and plays a
      critical role in facilitating orofacial hyperalgesia.

PMID- 16304629
TI  - Increased cell proliferation and granule cell number in the dentate gyrus of
      protein repair-deficient mice.
AB  - Recent studies have demonstrated that mice lacking protein L-isoaspartate (D
      aspartate) O-methyltransferase (Pcmt1-/- mice) have alterations in the insulin
      like growth factor-I (IGF-I) and insulin receptor pathways within the hippocampal
      formation as well as other brain regions. However, the cellular localization of
      these changes and whether the alterations might be associated with an increase in
      cell number within proliferative regions, such as the dentate gyrus, were
      unknown. In this study, stereological methods were used to demonstrate that these
      mice have an increased number of granule cells in the granule cell layer and
      hilus of the dentate gyrus. The higher number of granule cells was accompanied by
      a greater number of cells undergoing mitosis in the dentate gyrus, suggesting
      that an increase in neuronal cell proliferation occurs in this neurogenic zone of
      adult Pcmt1-/- mice. In support of this, increased doublecortin labeling of
      immature neurons was detected in the subgranular zone of the dentate gyrus. In
      addition, double immunofluorescence studies demonstrated that phosphorylated IGF
      I/insulin receptors in the subgranular zone were localized on immature neurons,
      suggesting that the increased activation of one or both of these receptors in
      Pcmt1-/- mice could contribute to the growth and survival of these cells. We
      propose that deficits in the repair of isoaspartyl protein damage leads to
      alterations in metabolic and growth-receptor pathways, and that this model may be
      particularly relevant for studies of neurogenesis that is stimulated by cellular
      damage.

PMID- 16304630
TI  - Segmental and laminar organization of the spinothalamic neurons in cat: evidence
      for at least five separate clusters.
AB  - The spinothalamic tract (STT), well known for its role in the relay of
      information about noxe, temperature, and crude touch, is usually associated with
      projections from lamina I, but spinothalamic neurons in other laminae have also
      been reported. In cat, no complete overview exists of the precise location and
      number of spinal cells that project to the thalamus. In the present study the
      laminar distribution of retrogradely labeled cells in all spinal segments (C1
      Coc2) was investigated after large WGA-HRP injections in the thalamus. The
      results show that this distribution of STT cells differed greatly between the
      different spinal segments. Quantitative analysis showed that there exist at least
      five separate clusters of spinothalamic neurons. Lamina I neurons in cluster A
      and lamina V neurons in cluster B are mainly found contralaterally throughout the
      length of the spinal cord. Cluster C neurons are located bilaterally in the
      ventrolateral part of laminae VI-VII and lamina VIII of the C1-C3 spinal cord.
      Cluster D neurons were found contralaterally in lamina VI in the C1-C2 segments,
      and cluster E neurons were located mainly contralaterally in the medial part of
      laminae VI-VII and lamina VIII of the lumbosacral cord. Most spinothalamic
      neurons are not located in the enlargements and most spinothalamic neurons are
      not located in lamina I, as suggested by several other authors. The location of
      the spinothalamic neurons shows remarkable similarities, but also differences,
      with the location of spino-periaqueductal gray neurons.

PMID- 16304631
TI  - Hormone complement of the Cancer productus sinus gland and pericardial organ: an
      anatomical and mass spectrometric investigation.
AB  - In crustaceans, circulating hormones influence many physiological processes. Two
      neuroendocrine organs, the sinus gland (SG) and the pericardial organ (PO), are
      the sources of many of these compounds. As a first step in determining the roles
      played by hemolymph-borne agents in the crab Cancer productus, we characterized
      the hormone complement of its SG and PO. We show via transmission electron
      microscopy that the nerve terminals making up each site possess dense-core and/or
      electron-lucent vesicles, suggesting diverse complements of bioactive molecules
      for both structures. By using immunohistochemistry, we show that small molecule
      transmitters, amines and peptides, are among the hormones present in these
      tissues, with many differentially distributed between the two sites (e.g.,
      serotonin in the PO but not the SG). With several mass spectrometric (MS)
      methods, we identified many of the peptides responsible for the immunolabeling
      and surveyed the SG and PO for peptides for which no antibodies exist. By using
      MS, we characterized 39 known peptides [e.g., beta-pigment-dispersing hormone
      (beta-PDH), crustacean cardioactive peptide, and red pigment-concentrating
      hormone] and de novo sequenced 23 novel ones (e.g., a new beta-PDH isoform and
      the first B-type allatostatins identified from a non-insect species).
      Collectively, our results show that diverse and unique complements of hormones,
      including many previously unknown peptides, are present in the SG and PO of C.
      productus. Moreover, our study sets the stage for future biochemical and
      physiological studies of these molecules and ultimately the elucidation of the
      role(s) they play in hormonal control in C. productus.

PMID- 16304632
TI  - An open letter to our readers on the use of antibodies.

PMID- 16304633
TI  - Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent
      neurons with adelta/c-fibers and colocalization with trk receptors.
AB  - The transient receptor potential (TRP) superfamily of cation channels contains
      four temperature-sensitive channels, named TRPV1-4, that are activated by heat
      stimuli from warm to that in the noxious range. Recently, two other members of
      this superfamily, TRPA1 and TRPM8, have been cloned and characterized as possible
      candidates for cold transducers in primary afferent neurons. Using in situ
      hybridization histochemistry and immunohistochemistry, we characterized the
      precise distribution of TRPA1, TRPM8, and TRPV1 mRNAs in the rat dorsal root
      ganglion (DRG) and trigeminal ganglion (TG) neurons. In the DRG, TRPM8 mRNA was
      not expressed in the TRPV1-expressing neuronal population, whereas TRPA1 mRNA was
      only seen in some neurons in this population. Both A-fiber and C-fiber neurons
      expressed TRPM8, whereas TRPV1 was almost exclusively seen in C-fiber neurons.
      All TRPM8-expressing neurons also expressed TrkA, whereas the expression of TRPV1
      and TRPA1 was independent of TrkA expression. None of these three TRP channels
      were coexpressed with TrkB or TrkC. The TRPM8-expressing neurons were more
      abundant in the TG compared with the DRG, especially in the mandibular nerve
      region innervating the tongue. Our data suggest heterogeneity of TRPM8 and TRPA1
      expression by subpopulations of primary afferent neurons, which may result in the
      difference of cold-sensitive primary afferent neurons in sensitivity to chemicals
      such as menthol and capsaicin and nerve growth factor.

PMID- 16304634
TI  - Cyanobacterial toxins--occurrence, biosynthesis and impact on human affairs.
AB  - Mass developments of cyanobacteria ("blue-green algae") in lakes and brackish
      waters have repeatedly led to serious concerns due to their frequent association
      with toxins. Among these are the widespread hepatotoxins microcystin (MC) and
      nodularin (NOD). Here, we give an overview about the ecostrategies of the diverse
      toxin-producing species and about the genes and enzymes that are involved in the
      biosynthesis of the cyclic peptides. We further summarize current knowledge about
      toxicological mechanisms of MC and NOD, including protein phosphatase inhibition,
      oxidative stress and their tumor-promoting capabilities. One biotransformation
      pathway for MC is described. Mechanisms of cyanobacterial neurotoxins (anatoxin
      a, homanatoxin-a, and anatoxin-a(s)) are briefly explained. We highlight selected
      cases of human fatalities related to the toxins. A special focus is given to
      evident cases of contamination of food supplements with cyanobacterial toxins,
      and to the necessary precautions.

PMID- 16304635
TI  - Resistance of regulatory T cells to glucocorticoid-induced [corrected] TNFR
      family-related protein (GITR) during Plasmodium yoelii infection.
AB  - CD4+ T cells are the major effector T cells against blood-stage Plasmodium yoelii
      infection. On the other hand, the lethal strain of P. yoelii (PyL) has acquired
      an escape mechanism from host T cell immunity by activating CD4+CD25+ regulatory
      T cells (Treg). Although the activation of Treg during PyL infection precludes
      the clearance of PyL from mice, it remains unclear whether activation of Treg is
      attributable to a specific response against PyL infection. Thus, we examined here
      whether Treg proliferate in an antigen-dependent manner during PyL infection. We
      also investigated the effector and regulatory mechanisms of Treg. Infection with
      PyL increased the number of CD4+CD25+ T cells, in which expression of Foxp3 mRNA
      is up-regulated. The Treg that were transferred into mice infected with PyL, but
      not with a non-lethal strain of P. yoelii (PyNL), proliferated during the initial
      5 days following infection. The Treg from PyL-infected mice showed strong
      suppression compared with those from naive or PyNL-infected mice, and could
      suppress T cell activation by recognizing PyL- but not PyNL-derived antigens.
      Furthermore, the suppressive function of Treg activated in PyL-infected but not
      in naive mice could not be inhibited by treatment with an anti-glucocorticoid
      induced TNFR family-related protein (GITR) mAb. These findings indicate that PyL
      infection specifically activates Treg that are specific for PyL-derived antigens.
      The infection also induces resistance for Treg to GITR signaling, and this
      eventually contributes to the escape of parasites from host T cell immunity.

PMID- 16304636
TI  - Differences in HCV-specific T cell responses between chronic HCV infection and
      HIV/HCV co-infection.
AB  - Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cell responses were investigated
      using a panel of 728 overlapping peptides spanning the whole HCV genome in 47 HCV
      mono-infected and 26 HIV/HCV co-infected individuals using the IFN-gamma ELISPOT
      assay and flow cytometry. The frequency of HCV-specific T cell responses was
      similar (approximately 40%) in both groups, but the breadth of the T cell
      responses tended to be reduced in HIV/HCV co-infected individuals. Of interest,
      23 new HCV-derived epitopes were identified, and CD4+ HCV-specific T cell
      responses were detected overall in a proportion similar to CD8+ T cell responses.
      A tendency towards a dominant CD8+ T cell response was associated with HIV/HCV co
      infection. HCV-specific CD8+ T cells secreted both IL-2 and IFN-gamma, although a
      reduction in the percentage of IL-2/IFN-gamma-secreting cells was observed in
      HIV/HCV co-infected individuals. The increase in CD4+ T cell counts after
      antiretroviral therapy in HIV/HCV co-infected individuals was not associated with
      restoration of HCV-specific T cell responses. Altogether, these results provide
      new insights into the characterization of HCV-specific T cell responses in HCV
      mono-infected and HIV/HCV co-infected individuals.

PMID- 16304637
TI  - Collagen type I signaling reduces the expression and the function of human
      receptor activator of nuclear factor-kappa B ligand (RANKL) in T lymphocytes.
AB  - The mechanisms by which beta1 integrins modulate T cell functions are still
      poorly defined. We have previously reported that signaling via the collagen type
      I (Coll I) receptor, alpha2beta1 integrin, inhibited FasL expression and
      protected Jurkat T cells from activation-induced cell death (AICD). In this
      study, we examined whether Coll I signaling in T cells also modulates the
      expression of the human receptor activator of nuclear factor-kappaB ligand
      (RANKL), a recently identified TNF family member which has important functions in
      osteoclastogenesis, cell survival and apoptosis. Our results show that in both
      Jurkat T cells and human primary T cells, Coll I signaling significantly reduces
      activation-induced RANKL expression by 50-60%. We also found that RANKL is not
      involved in AICD but participates in doxorubicin-induced apoptosis of leukemia T
      cell lines including Jurkat, CEM and HSB-2. In this respect, Coll I protected
      leukemia T cell lines from doxorubicin-induced apoptosis by inhibiting
      doxorubicin-induced RANKL expression. Together, our results suggest that by
      limiting the production of RANKL, Coll I signaling may contribute to the
      resistance of leukemia T cells to chemotherapy. Our study also emphasizes the
      importance Coll I signaling may have in the control of RANKL-associated T cell
      functions.

PMID- 16304638
TI  - Selective expansion and engraftment of human CD16+ NK cells in NOD/SCID mice.
AB  - NK cells are large granular lymphocytes that represent a critical component of
      the innate immunity. Investigations of human NK cell function are largely based
      on in vitro assays because of the lack of suitable animal models. Here we have
      established conditions leading to the development of human NK cells in NOD/SCID
      (severe combined immunodeficiency) mice receiving grafts of cord blood
      mononuclear cells (CBMC), and GFP-transduced HFWT inducing NK cells (GHINK-1),
      which have been shown to support the selective expansion of NK cells from human
      PBMC and CBMC in vitro. Significant numbers of CD56dimCD16+ cytotoxic and CD56
      CD16+ immature NK cells appeared in peripheral blood (PB), peritoneal cavity,
      spleen, bone marrow and liver of the mice. The newly generated NK cells did not
      express activation markers such as CD25, CD69 and NKp44, the expression of which
      was augmented by IL-2 in vitro. The NOD/SCID mice engrafted with human NK cells
      exhibited antitumor activity against K562 erythroleukemia in vitro and in vivo.
      Thus, we succeeded in developing a CD56dimCD16+ cytotoxic NK cell populations in
      NOD/SCID mice closely resembling the main NK fraction in human PB and CD56-CD16+
      immature NK cells. Our model provides not only information about the development
      and dynamics of physiological human NK cells but also an important pre-clinical
      system for immunotherapeutic strategies.

PMID- 16304639
TI  - Activation of invariant NK T cells protects against experimental rheumatoid
      arthritis by an IL-10-dependent pathway.
AB  - Invariant natural killer T (iNKT) cells are a unique lymphocyte subtype
      implicated in the regulation of autoimmunity and a good source of protective Th2
      cytokines. Agonist alpha-galactosylceramide (alpha-GalCer) of iNKT cells exert a
      therapeutical effect in type 1 diabetes. We investigated whether iNKT activation
      with alpha-GalCer was protective in collagen-induced arthritis (CIA) in DBA/1
      mice, a standard model of rheumatoid arthritis. Here, we have shown that in vivo
      iNKT cell function was altered in DBA/1 mice since stimulation with alpha-GalCer
      led to decreased IL-4 and IFN-gamma levels in sera, as compared with C57BL/6
      mice. alpha-GalCer induced a clear-cut diminution of clinical and histological
      arthritides. An anti-IL-10 receptor antibody abrogated the protective effect of
      alpha-GalCer, suggesting a key role for IL-10 in the protection against CIA by
      activated iNKT cells. Confirming these data, disease protection conferred by
      alpha-GalCer correlated with the ability of LN CD4+ cells to secrete larger
      amounts of IL-10. These findings suggest that in CIA susceptibility to
      autoimmunity is associated with dysfunctions of iNKT cells. Our demonstration
      that iNKT cell activation by alpha-GalCer remains efficient in CIA-prone DBA/1
      mice to provide protective IL-10 suggests that this could be used therapeutically
      to treat autoimmune arthritis.

PMID- 16304640
TI  - Structure of a ribulose 5-phosphate 3-epimerase from Plasmodium falciparum.
AB  - The crystal structure of Pfal009167AAA, a putative ribulose 5-phosphate 3
      epimerase (PfalRPE) from Plasmodium falciparum, has been determined to 2 A
      resolution. RPE represents an exciting potential drug target for developing
      antimalarials because it is involved in the shikimate and the pentose phosphate
      pathways. The structure is a classic TIM-barrel fold. A coordinated Zn ion and a
      bound sulfate ion in the active site of the enzyme allow for a greater
      understanding of the mechanism of action of this enzyme. This structure is solved
      in the framework of the Structural Genomics of Pathogenic Protozoa (SGPP)
      consortium.

PMID- 16304641
TI  - Comparative structure-function analysis of cytolethal distending toxins.
AB  - Cytolethal distending toxins (CDTs) constitute a family of bacterial proteins
      that enter eukaryotic cells with genotoxic activity leading to cell cycle arrest
      and apoptosis. CDTs are widespread, having been found in a variety of Gram
      negative pathogens with a broad tissue tropism. The recently determined crystal
      structure of the Haemophilus ducreyi CDT provides a powerful starting point for
      analysis of the structure and function in this toxin family. In this study, we
      apply comparative modeling and structural analysis to extend the experimental
      structural information to multiple CDT toxins from a diverse species. Analysis of
      structurally and functionally important residues in the active subunit, CdtB, and
      putative cell delivery elements, CdtA and CdtC, begins to establish the
      fundamental, mechanistic elements of this unique holotoxin. The results reveal
      that key structural features with important functional consequences are highly
      conserved across different CDTs, providing a blueprint for directed examination
      of functional hypotheses in a variety of pathogenic contexts.

PMID- 16304642
TI  - Ir-catalysed asymmetric hydrogenation: Ligands, substrates and mechanism.
AB  - Relatively air and moisture tolerant cationic iridium complexes, with chiral non
      racemic N,P-ligands and weakly coordinating counter ions, are efficient catalysts
      in the asymmetric hydrogenation of olefins. Unfunctionalised olefins are
      particularly difficult substrates because, in general, a polar group adjacent to
      the alkene bond is required for high catalytic activity and enantioselectivity.
      The applicability towards a variety of substrates and choice of ligands reported
      thus far in the literature, as well as the mechanism, selectivity issues and the
      importance of the anion are also discussed.

PMID- 16304643
TI  - Ruthenium-cluster-mediated activation of all bonds of a methyl group of 6,6'
      dimethyl-2,2'-bipyridine and 2,9-dimethyl-1,10-phenanthroline: transformation of
      the latter into a 2-alkenyl-9-methyl-1,10-phenanthroline ligand.
AB  - The treatment of [Ru3(CO)12] with 6,6'-dimethyl-2,2'-bipyridine (Me2bipy) or 2,9
      dimethyl-1,10-phenanthroline (Me2phen) in THF at reflux temperature gives the
      trinuclear dihydride complexes [Ru3(mu-H)2(mu3-L1)(CO)8] (L1 = HCbipyMe 1 a,
      HCphenMe 1 b), which result from the activation of two C-H bonds of a methyl
      group. The hexa-, hepta-, and pentanuclear derivatives [Ru6(mu3-H)(mu5-L2)(mu
      CO)3(CO)13] (L2 = CbipyMe 2 a, CphenMe 2 b), [Ru7(mu3-H)(mu5-L2)(mu-CO)2(CO)16]
      (L2 = CbipyMe 3 a, CphenMe 3 b), and [Ru5(mu-H)(mu5-C)(mu-L3)(CO)13] (L3 = bipyMe
      4 a, phenMe 4 b) can also be obtained by treating 1 a and 1 b with [Ru3(CO)12].
      Compounds 2 a and 2 b have a basal edge-bridged square-pyramidal metallic
      skeleton with a carbyne-type C atom capping the four Ru atoms of the pyramid
      base. The structures of 3 a and 3 b are similar to those of 2 a and 2 b,
      respectively, but an additional Ru atom now caps a triangular face of the square
      pyramidal fragment of the metallic skeleton. The most interesting feature of 2 a,
      2 b, 3 a, and 3 b is that their carbyne-type C atoms were originally bound to
      three hydrogen atoms in Me2bipy or Me2phen and, therefore, they arise from the
      unprecedented activation of all three C-H bonds of C-bound methyl groups. The
      pentanuclear compounds 4 a and 4 b contain a carbide ligand surrounded by five Ru
      atoms in a distorted trigonal-bipyramidal environment. They are the products of a
      series of processes that includes the activation of all bonds (three C-H and one
      C-C) of organic methyl groups, and are the first examples of complexes having
      carbide ligands that arise from C-bonded methyl groups. The alkenyl derivatives
      [Ru5(mu5-C)(mu-p-MeC6H4CHCHphenMe)(CO)13] (5 b), [Ru5(mu-H)(mu5-C)(mu-p
      MeC6H4CHCHphenMe)(p-tolC2)(CO)12] (6 b), and [Ru5(mu-H)(mu5-C)(mu
      PhCHCHphenMe)(PhC2)(CO)12] (7 b) have been obtained by treating 4 b with p-tolyl-
      and phenylacetylene, respectively. Their heterocyclic ligands contain an alkenyl
      fragment in the position that was originally occupied by a methyl group.
      Therefore, these complexes are the result of the formal substitution of an
      alkenyl group for a methyl group of 2,9-dimethyl-1,10- phenanthroline.

PMID- 16304644
TI  - Nucleic acid intercalators and avidin probes derived from luminescent
      cyclometalated iridium(III)-dipyridoquinoxaline and -dipyridophenazine complexes.
AB  - Six luminescent cyclometalated iridium(III)-dipyridoquinoxaline and 
      dipyridophenazine complexes [Ir(ppy)2(N-N)](PF6) (Hppy = 2-phenylpyridine; N-N =
      dipyrido[3,2-f:2',3'-h]quinoxaline, dpq (1); 2-n-butylamidodipyrido[3,2-f:2',3'
      h]quinoxaline, dpqa (2); 2-((2-biotinamido)ethyl)amidodipyrido[3,2-f:2',3'
      h]quinoxaline, dpqB (3); dipyrido[3,2-a:2',3'-c]phenazine, dppz (4);
      benzo[i]dipyrido[3,2-a:2',3'-c]phenazine, dppn (5); 11-((2
      biotinamido)ethyl)amidodipyrido[3,2-a:2',3'-c]phenazine, dppzB (6)) have been
      designed as luminescent intercalators for DNA and probes for avidin. The
      structure of complex 4 has been studied by X-ray crystallography. The
      photophysical and electrochemical properties of the complexes have also been
      investigated. The binding of these complexes to double-stranded calf thymus DNA
      and synthetic double-stranded oligonucleotides poly(dA) x poly(dT) and poly(dG) x
      poly(dC) has been investigated by spectroscopic titrations. The interactions
      between the two biotin-containing complexes and avidin have been studied by 4'
      hydroxyazobenzene-2-carboxylic acid (HABA) assays and emission titrations.

PMID- 16304645
TI  - Stabilisation of methylene radicals by cob(II)alamin in coenzyme B12 dependent
      mutases.
AB  - Coenzyme B12 initiates radical chemistry in two types of enzymatic reactions, the
      irreversible eliminases (e.g., diol dehydratases) and the reversible mutases
      (e.g., methylmalonyl-CoA mutase). Whereas eliminases that use radical generators
      other than coenzyme B12 are known, no alternative coenzyme B12 independent
      mutases have been detected for substrates in which a methyl group is reversibly
      converted to a methylene radical. We predict that such mutases do not exist.
      However, coenzyme B12 independent pathways have been detected that circumvent the
      need for glutamate, beta-lysine or methylmalonyl-CoA mutases by proceeding via
      different intermediates. In humans the methylcitrate cycle, which is ostensibly
      an alternative to the coenzyme B12 dependent methylmalonyl-CoA pathway for
      propionate oxidation, is not used because it would interfere with the Krebs cycle
      and thereby compromise the high-energy requirement of the nervous system. In the
      diol dehydratases the 5'-deoxyadenosyl radical generated by homolysis of the
      carbon-cobalt bond of coenzyme B12 moves about 10 A away from the cobalt atom in
      cob(II)alamin. The substrate and product radicals are generated at a similar
      distance from cob(II)alamin, which acts solely as spectator of the catalysis. In
      glutamate and methylmalonyl-CoA mutases the 5'-deoxyadenosyl radical remains
      within 3-4 A of the cobalt atom, with the substrate and product radicals
      approximately 3 A further away. It is suggested that cob(II)alamin acts as a
      conductor by stabilising both the 5'-deoxyadenosyl radical and the product
      related methylene radicals.

PMID- 16304646
TI  - A method for localizing ligand binding pockets in protein structures.
AB  - The accurate identification of ligand binding sites in protein structures can be
      valuable in determining protein function. Once the binding site is known, it
      becomes easier to perform in silico and experimental procedures that may allow
      the ligand type and the protein function to be determined. For example, binding
      pocket shape analysis relies heavily on the correct localization of the ligand
      binding site. We have developed SURFNET-ConSurf, a modular, two-stage method for
      identifying the location and shape of potential ligand binding pockets in protein
      structures. In the first stage, the SURFNET program identifies clefts in the
      protein surface that are potential binding sites. In the second stage, these
      clefts are trimmed in size by cutting away regions distant from highly conserved
      residues, as defined by the ConSurf-HSSP database. The largest clefts that remain
      tend to be those where ligands bind. To test the approach, we analyzed a
      nonredundant set of 244 protein structures from the PDB and found that SURFNET
      ConSurf identifies a ligand binding pocket in 75% of them. The trimming procedure
      reduces the original cleft volumes by 30% on average, while still encompassing an
      average 87% of the ligand volume. From the analysis of the results we conclude
      that for those cases in which the ligands are found in large, highly conserved
      clefts, the combined SURFNET-ConSurf method gives pockets that are a better match
      to the ligand shape and location. We also show that this approach works better
      for enzymes than for nonenzyme proteins.

PMID- 16304647
TI  - Rediscovery, isolation, and asymmetric reduction of 1,2,3,4-tetrahydronaphthalene
      1,4-dione and studies of its [Cr(CO)3] complex.

PMID- 16304648
TI  - A general and efficient method for the formylation of aryl and heteroaryl
      bromides.

PMID- 16304649
TI  - The photochemical reactivity of the "photo-inert" tungsten (Fischer) carbene
      complexes.

PMID- 16304650
TI  - Corrosion-based synthesis of single-crystal Pd nanoboxes and nanocages and their
      surface plasmon properties.

PMID- 16304651
TI  - The autoionization of [TiF4] by cation complexation with [15]crown-5 to give
      [TiF2([15]crown-5)][Ti4F18] containing the tetrahedral [Ti4F18]2- ion.

PMID- 16304652
TI  - Quasi-homogeneous methanol synthesis over highly active copper nanoparticles.

PMID- 16304653
TI  - Dangling arms: a tetrahedral supramolecular host with partially encapsulated
      guests.

PMID- 16304654
TI  - Cobalt-catalyzed carbonylative copolymerization of N-alkylazetidines and
      tetrahydrofuran.

PMID- 16304655
TI  - Efficient enzymatic synthesis of phosphoroselenoate RNA by using adenosine 5'
      (alpha-P-seleno)triphosphate.

PMID- 16304656
TI  - Assembly of dendrimers with redox-active [{CpFe(mu3-CO)}4] clusters at the
      periphery and their application to oxo-anion and adenosine-5'-triphosphate
      sensing.

PMID- 16304657
TI  - Controlling polymer architecture through host-guest interactions.

PMID- 16304658
TI  - Li2B12C2 and LiB13C2: colorless boron-rich boride carbides of lithium.

PMID- 16304659
TI  - In situ NMR spectroscopic observation of a catalytic intermediate in phosphine
      catalyzed cyclo-oligomerization of isocyanates.

PMID- 16304660
TI  - Step-by-step assembly of trivacant tungstosilicates: synthesis and
      characterization of tetrameric anions.

PMID- 16304661
TI  - Diels-Alder reactivity of binuclear complexes with calixarene-like structures.

PMID- 16304662
TI  - Nanoparticles as recyclable catalysts: the frontier between homogeneous and
      heterogeneous catalysis.
AB  - Interest in catalysis by metal nanoparticles (NPs) is increasing dramatically, as
      reflected by the large number of publications in the last five years. This field,
      "semi-heterogeneous catalysis", is at the frontier between homogeneous and
      heterogeneous catalysis, and progress has been made in the efficiency and
      selectivity of reactions and recovery and recyclability of the catalytic
      materials. Usually NP catalysts are prepared from a metal salt, a reducing agent,
      and a stabilizer and are supported on an oxide, charcoal, or a zeolite. Besides
      the polymers and oxides that used to be employed as standard, innovative
      stabilizers, media, and supports have appeared, such as dendrimers, specific
      ligands, ionic liquids, surfactants, membranes, carbon nanotubes, and a variety
      of oxides. Ligand-free procedures have provided remarkable results with extremely
      low metal loading. The Review presents the recent developments and the use of NP
      catalysis in organic synthesis, for example, in hydrogenation and C--C coupling
      reactions, and the heterogeneous oxidation of CO on gold NPs.

PMID- 16304663
TI  - Differential-frequency saturation transfer difference NMR spectroscopy allows the
      detection of different ligand-DNA binding modes.

PMID- 16304664
TI  - Pediatric paraganglioma: an early manifestation of an adult disease secondary to
      germline mutations.
AB  - BACKGROUND: Paraganglioma (PGL) and phaeochromocytoma (PCC) are chemotherapy and
      radiation-resistant neuroendocrine tumors that arise from sympathetic tissue, and
      rarely occur in children. PCC may be associated with predisposing (germline)
      conditions like the multiple endocrine neoplasia type 2 (MEN2; OMIM 164761), von
      Hippel-Lindau syndrome (VHL; OMIM 193300), and rarely neurofibromatosis type 1
      syndrome (NF1; OMIM 162200) and multiple endocrine neoplasia type 1 (MEN1; OMIM
      131100). PGL, on the other hand, may be related to predisposing germline
      conditions like the familial PGL syndrome and the NF1 syndrome. In adult studies,
      one of the highest predisposing factors for germline mutation among patients
      presenting apparently sporadic PCC/PGL was their age at presentation. The aim of
      this study was to determine the rate of germline mutations among the rare
      patients presenting with sporadic PGL during childhood. PROCEDURE: In this study,
      we report the genetic analysis for predisposing conditions for the only three PGL
      cases retrospectively identified at our pediatric institution in the last 20
      years. RESULTS: None had NF1 clinical associated lesions. Mutation screening of
      genes associated to VHL (VHL), MEN (RET), and familial PGL (SDH-B, -C, and -D)
      showed that all cases had germline deletions in the SDHB gene. We report a novel
      mutation, c.778 del C. Importantly, several non-symptomatic relatives were found
      to be carriers, thus ensuring them a clinical follow-up. CONCLUSION: According to
      our findings, PGL presenting during childhood represents an early manifestation
      of an adult disease caused by predisposing germline mutations. These results
      underline the importance of genetic studies in pediatric PGLs.

PMID- 16304665
TI  - Establishment of a pediatric HSCT program in a public hospital in Chile.
AB  - BACKGROUND: In Chile, survival estimates for pediatric patients with cancer are
      comparable to those in the United States and Western Europe. Approximately 80% of
      these patients are treated at government-supported centers, and an estimated 65%
      are cured. We reasoned that cure rates could be further improved if
      transplantation with hematopoietic stem cells were available for patients with
      chemotherapy-resistant malignancy. PATIENTS AND METHODS: Physicians and nurses
      were selected to be trained in international centers, and a transplantation unit
      was developed at Luis Calvo Mackenna Hospital in Santiago. Between October 1999
      and December 2003, 59 patients received transplants. Of these, 42 were from HLA
      matched family members and 11 were autologous. RESULTS: The 3-year event-free
      survival estimate was 72 +/- 10% overall, and it was 81 +/- 10% for the subgroup
      treated with matched related transplants. Peritransplant mortality was 6.6%. The
      average cost for an allogeneic transplant in our unit was 50,000 US dollars.
      CONCLUSIONS: We are encouraged by this experience as well as by the overall
      survival rates and hope to expand the program. Our goal is to extend treatment to
      all children in the country for whom HSCT is indicated, including those who do
      not have HLA-identical family donors.

PMID- 16304666
TI  - Safety and efficacy of a continuous infusion, patient-controlled antiemetic pump
      for children receiving emetogenic chemotherapy.
AB  - BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is one of the most
      distressing side effects of moderately or highly emetogenic chemotherapy.
      Diphenhydramine, lorazepam, and dexamethasone have been used individually to
      treat CINV. The objective of this study was to evaluate the safety and potential
      efficacy of those drugs administered via a patient controlled pump (BAD pump) to
      control CINV. PROCEDURE: A retrospective chart review was conducted of all
      pediatric oncology patients who received the BAD pump. Emetic episodes, doses of
      rescue medications to treat breakthrough nausea or vomiting, and occurrence of
      adverse events were recorded. Complete response (CR) was defined as no emesis or
      rescue medications, partial response (PR) as emesis but no rescue medications,
      and failure (F) as rescue medications required. RESULTS: Thirty patients received
      a total of 141 courses. Adverse events occurred in 4.2% of the courses; confusion
      (n = 2), depressed mood (n = 1), dysphoria (n = 1), agitation (n = 1), and
      restlessness (n = 1). All side effects resolved after decreasing the infusion
      rate, and the pump was not discontinued in any patients. Eighteen patients failed
      conventional prophylaxis and received BAD pump for identical subsequent
      chemotherapy cycles; they spent more days in CR with BAD pump than without it, 21
      versus 45 days (P = .003) respectively. Patients receiving BAD pump had
      significantly shorter hospital stay with BAD pump than those not receiving it, 68
      days versus 76 (P = .046). CONCLUSIONS: BAD pump is well tolerated in pediatric
      patients receiving chemotherapy and may be more effective than conventional
      prophylaxis in controlling CINV in some patients.

PMID- 16304667
TI  - Genetic causes of familial risk in rhabdoid tumors.

PMID- 16304668
TI  - Metabolism of arsenic in Drosophila melanogaster and the genotoxicity of
      dimethylarsinic acid in the Drosophila wing spot test.
AB  - Inorganic arsenic is nongenotoxic in the Drosophila melanogaster wing somatic
      mutation and recombination test (SMART). Recent evidence in mammalian systems
      indicates that methylated metabolites of arsenic are more genotoxic than
      inorganic arsenic. Thus, we hypothesized that inorganic arsenic is nongenotoxic
      in Drosophila because they are unable to biotransform arsenic to methylated
      forms. In the present study, we fed trivalent and pentavalent inorganic arsenic
      to Drosophila larvae and adults and measured the production of methylated
      derivatives. No biomethylated arsenic species were found in the organisms or in
      the growth medium, which suggests that Drosophila are unable to biomethylate
      inorganic arsenic. Exposure of Drosophila to the methylated arsenic derivative
      dimethylarsinic acid (DMA(V)) resulted in incorporation of this organoarsenic
      compound without demethylation. In addition, we used the SMART wing spot assay,
      which measures loss of heterozygosity (LOH) resulting from gene mutation,
      chromosomal rearrangement, chromosome breakage, and chromosome loss, to evaluate
      the genotoxicity of DMA. DMA by itself induced significant increases in the
      frequency of total spots, small spots, and large single spots. These results are
      consistent with the important role of arsenic biomethylation as a determinant of
      the genotoxicity of arsenic compounds. The absence of biomethylation in
      Drosophila could explain the lack of genotoxicity for inorganic arsenic and the
      genotoxicity of methylated arsenic species in the SMART wing spot assay.

PMID- 16304669
TI  - Variability in fecal water genotoxicity, determined using the Comet assay, is
      independent of endogenous N-nitroso compound formation attributed to red meat
      consumption.
AB  - Red meat consumption causes a dose-dependent increase in fecal apparent total N
      nitroso compounds (ATNC). The genotoxic effects of these ATNCs were investigated
      using two different Comet assay protocols to determine the genotoxicity of fecal
      water samples. Fecal water samples were obtained from two studies of a total of
      21 individuals fed diets containing different amounts of red meat, protein, heme,
      and iron. The first protocol incubated the samples with HT-29 cells for 5 min at
      4 degrees C, whereas the second protocol used a longer exposure time of 30 min
      and a higher incubation temperature of 37 degrees C. DNA strand breaks were
      quantified by the tail moment (DNA in the comet tail multiplied by the comet tail
      length). The results of the two Comet assay protocols were significantly
      correlated (r = 0.35, P = 0.003), however, only the second protocol resulted in
      detectable levels of DNA damage. Inter-individual effects were variable and there
      was no effect on fecal water genotoxicity by diet (P > 0.20), mean transit time
      (P = 0.588), or weight (P = 0.705). However, there was a highly significant
      effect of age (P = 0.019). There was no significant correlation between
      concentrations of ATNCs in fecal homogenates and fecal water genotoxicity (r =
      0.04, P = 0.74). ATNC levels were lower in fecal water samples (272 microg/kg)
      compared to that of fecal homogenate samples (895 microg/kg) (P < 0.0001).
      Failure to find dietary effects on fecal water genotoxicity may therefore be
      attributed to individual variability and low levels of ATNCs in fecal water
      samples.

PMID- 16304670
TI  - Genotoxicity of hydrochlorothiazide in cultured human lymphocytes. I. Evaluation
      of chromosome delay and chromosome breakage.
AB  - Hypertension is often treated with diuretics, like hydrochlorothiazide (HCTZ).
      Previous results on the in vitro genotoxicity of HCTZ are equivocal. In the
      present study, we have evaluated the genotoxicity of HCTZ in cultured human
      lymphocytes using the Cytokinesis Blocked Micronucleus (CBMN) assay. In addition,
      micronucleus (MN) induction was analyzed by Fluorescence In Situ Hybridization
      (FISH) with an alpha-satellite DNA centromeric probe to distinguish between
      clastogenic and aneugenic effects. Lymphocyte cultures from 32 healthy adults
      were exposed to 5 and 40 microg/ml HCTZ. Age, gender, and smoking were evaluated
      as factors affecting the MN analysis. We found that HCTZ increased MN
      frequencies. FISH analysis revealed that HCTZ exerts its genotoxicity more
      strongly at the 40 microg/ml concentration, and principally through chromosome
      delay (aneugenicity). Multiregression analysis of our results confirmed the known
      effect of age and gender on MN induction in human lymphocytes. Smoking was also a
      confounding factor for MN induction, especially for centromere-negative MN
      frequencies. Under the experimental conditions used, only age had a clear
      positive effect on the response of lymphocytes to HCTZ. These data indicate that
      HCTZ produces micronuclei in cultured human lymphocytes by a mechanism that
      involves chromosome delay and to a lesser extent through chromosome breakage.

PMID- 16304671
TI  - Physiological studies of eicosapentaenoic acid production in the marine microalga
      Glossomastix chrysoplasta.
AB  - We describe the characterization of the microalga Glossomastix chrysoplasta, an
      eicosapentaenoic acid (EPA) producer in the Pinguiophyceae class, Chromophyte
      division. Growth conditions were selected to optimize algal growth and EPA
      production. EPA represented up to 30% of the fatty acid content of Glossomastix
      chrysoplasta, at levels of 22 mg EPA per gram dry weight. Up to 72% of the EPA
      was produced as glycolipids, components of structural lipids. The optimal growth
      conditions in continuous culture were found to be greater than 500 micromol
      photons/m(2) . s light intensity, 0.33/day dilution rate, pH 7.20-7.45, and a
      temperature of 18-20 degrees C. Macronutrient studies indicated the limiting
      nutrient to be bicarbonate or dissolved carbon dioxide, and consequently
      decreasing pH increased EPA production.

PMID- 16304672
TI  - Design and performance of a 24-station high throughput microbioreactor.
AB  - Two prototype 24-unit microbioreactors are presented and reviewed for their
      relative merits. The first used a standard 24-well plate as the template, while
      the second consisted of 24-discrete units. Both systems used non-invasive optical
      sensors to monitor pH and dissolved oxygen. The systems were used to cultivate
      Escherichia coli. Both designs had their merits and the results obtained are
      presented. In addition, dissolved oxygen control was demonstrated at the
      milliliter scale and 24 simultaneously monitored fermentations were successfully
      carried out. These results demonstrated high quality high throughput
      bioprocessing and provide important insights into operational parameters at small
      scale.

PMID- 16304673
TI  - Desmopressin treatment in nocturia; an analysis of risk factors for hyponatremia.
AB  - AIMS: To explore the incidence, severity, time course, and risk factors of
      clinically significant hyponatremia in desmopressin treatment for nocturia.
      METHODS: Data from three multi-center phase III trials were pooled. Hyponatremia
      was categorised as borderline (134-130 mmol/L) or significant (<130 mmol/L). Risk
      factors were explored with logistic regression and subgroup analysis performed to
      explore threshold values for contra-indication. RESULTS: In total 632 patients
      (344 men, 288 women) were analyzed. During dose-titration, serum sodium
      concentration below normal range was recorded in 95 patients (15%) and 31
      patients (4.9%) experienced significant hyponatremia. The risk increased with
      age, lower serum sodium concentration at baseline, higher basal 24-hr urine
      volume per bodyweight and weight gain at time of minimum serum sodium
      concentration. Age was the best single predictor. Elderly patients (>or=65 years
      of age) with a baseline serum sodium concentration below normal range were at
      high risk (75%). Limiting treatment in elderly with normal basal serum sodium
      concentration to those below 79 years and with a 24-hr urine output below 28
      ml/kg would reduce the risk from 8.1% to 3.0% at the cost of 34% fulfilling the
      contra-indication. CONCLUSIONS: The majority of nocturia patients tolerate
      desmopressin treatment without clinically significant hyponatremia. However, the
      risk increases with increasing age and decreasing baseline serum sodium
      concentration. Treatment of nocturia in elderly patients with desmopressin should
      only be undertaken together with careful monitoring of the serum sodium
      concentration. Patients with a baseline serum sodium concentration below normal
      range should not be treated.

PMID- 16304675
TI  - Muscarinic receptor transcript and protein density in hypertrophied and atrophied
      rat urinary bladder.
AB  - AIMS: Our previous studies showed that bladder hypertrophy shifts the muscarinic
      receptor subtype mediating contraction from M(3) towards M(2) along with
      increased M(2) and decreased M(3) protein concentration. We quantified mRNA for
      M(1) through M(5) receptors to determine whether the changes in M(2) and M(3)
      protein levels was due to changes in transcription. METHODS: Bladder hypertrophy
      was induced by bladder outlet obstruction (BOO), major pelvic ganglion
      electrocautery (DEN), and major pelvic ganglion decentralization (DEC). Bladder
      atrophy was induced by ureteral diversion (DIV). Additional groups included
      denervated and diverted (DEN-DIV), sham operated (SHAM), and normal (NOR)
      controls. Transcripts were quantified using a multiplex ribonuclease protection
      assay (RPA) and receptor protein density was determined by immunoprecipitation.
      Receptor transcripts were expressed per unit total RNA. RESULTS: Although all
      five receptor subtype transcripts were detected in all experimental groups, the
      densities of M(1), M(4), and M(5) were much lower than for the M(2) and M(3)
      subtype. There were more M(2) receptor transcripts than all the others,
      consistent with M(2) protein determinations. M(2) transcripts were significantly
      increased in DEN and BOO bladders. Surprisingly, M(3) transcripts were also
      significantly increased in BOO. There was a significant correlation (r=0.98,
      P<0.001) between protein density and transcript density for the M(2) but not the
      M(3) receptor among the different experimental groups. CONCLUSIONS: Changes in
      mRNA concentration are reflected by changes in protein density for the M(2)
      receptor but not for the M(3) receptor. Extrapolation of functional effects from
      transcript density data is invalid for M(3) mediated bladder contractions.

PMID- 16304674
TI  - Interrater reliability and physical examination of the pubovisceral portion of
      the levator ani muscle, validity comparisons using MR imaging.
AB  - AIMS: Defects in the pubovisceral portion of the levator ani muscle are seen with
      MR imaging. This study aims to determine interrater reliability of physical
      examination in detecting these defects, and to validate findings from physical
      examination using comparisons with MR images. METHODS: Two examiners palpated the
      pubovisceral muscles of 29 women to assess for defects in this muscle. Each
      examiner was blinded to the others findings. MR scans were acquired on a further
      24 women after structured clinical examination by one examiner. These images were
      read to determine pubovisceral muscle defects, blinded to patient identifiers.
      Agreement between raters and between MR imaging and clinical examination were
      calculated. RESULTS: The two examiners had positive agreement (presence of a
      defect) of 72.7% and negative agreement (absence of a defect) of 83.3%. The
      positive agreement between physical examination and MR imaging was 27.3% and the
      negative agreement 86.5%. CONCLUSION: The structured physical examination to
      detect defects in the pubovisceral portion of the levator ani muscle can be
      learned as shown by good interrater agreement. However, examination alone
      underestimates these defects compared with MR imaging.

PMID- 16304676
TI  - Development and assessment of an innovative soil-washing process based on the use
      of cholic acid-derivatives as pollutant-mobilizing agents.
AB  - Surfactant-aided soil washing is often proposed for the restoration of aged
      organic pollutant-contaminated soils. As many of commercial surfactants have been
      found to be toxic and recalcitrant, the opportunity to use in this process cheap,
      non-toxic, and biodegradable pollutant-mobilizing agents, such as deoxycholic
      acid (DA), bovine bile (BB), and the residue resulting from DA extraction from BB
      (BBR), was studied in this work. A soil historically contaminated by chlorinated
      anilines and benzenes, thiophenes, and several polycyclic aromatic hydrocarbons
      was suspended at 15% w/v and washed in water or water amended at 1.0% (w/v) with
      DA, BB, BBR, or Triton X-100 (TX). The resulting effluents were supplemented with
      nutrients and subjected to aerobic bioremediation. The biogenic agents enhanced
      the water pollutant elution potential by 230/440%. TX enhanced the same parameter
      by about 540%; however, it mediated a lower depletion of the initial soil
      ecotoxicity and a more extensive mobilization of soil constituents with respect
      to the biogenic agents. Furthermore, TX adversely affected the biotreatability of
      resulting effluents, by adversely affecting the growth of cultivable bacterial
      biomass and the structure of eubacterial community of the effluent. On the
      contrary, the biogenic agents, and in particular DA and BB, enhanced the
      effluents bioremediation, by sustaining the growth and increasing the complexity
      of the effluent eubacterial communities. Thus, DA and BB are very promising
      additives for an effective and environmental friendly soil washing treatment of
      aged (chloro)organics contaminated soils.

PMID- 16304677
TI  - Contractile properties of the proximal urethra and bladder in female pig:
      morphology and function.
AB  - AIMS: To compare the contractile properties of proximal urethral and bladder
      muscle of the female pig. MATERIALS AND METHODS: In two proximal segments (I and
      II) of the urethra, small muscle bundles were excised to measure the force-length
      (maximum force) and the force-velocity (unloaded shortening velocity) relation
      using the stop-test. The rate of force development was calculated using phase
      plots. Contractile properties of urethral and bladder segments were statistically
      compared using the Mann-Whitney U-test. Immunohistochemical staining of whole
      circumference urethral cross sections was used to identify the location of smooth
      and striated muscle fibres. RESULTS: On isometric force development, the urethral
      muscle bundles revealed a fast ( approximately 0.5 sec) and a slow (
      approximately 2.1 sec) time constant, whereas in bladder only a slow (
      approximately 2.3 sec) component was measured. On average, isometric force was
      highest in bladder. The length range over which force was produced was smallest
      in urethral segment II, followed by urethral segment I and finally bladder. The
      unloaded shortening velocity was 0.15, 0.25 and 0.35 1/sec, respectively.
      Histological preparations showed that smooth as well as striated muscle was
      present in proximal urethra. In urethral muscle bundles, spontaneous contractions
      were measured with a frequency of 0.4 Hz. CONCLUSIONS: Differences in
      contractility found between urethra and bladder may be ascribed to the presence
      of striated muscle in the proximal urethra. The regulation of tone and
      spontaneous contractions may be part of the continence mechanism in the female
      pig urinary tract.

PMID- 16304679
TI  - Anatomy of the Hesse photoreceptor cell axonal system in the central nervous
      system of amphioxus.
AB  - The present study reports the organization of the Hesse cell axonal system in the
      central nervous system of the amphioxus, with the use of a polyclonal antiserum
      raised against lamprey gonadotropin-releasing hormone-I (GnRH-I). In the spinal
      cord, the rhabdomeric photoreceptor cells of the bicellular organs were well
      labeled with this antibody. These cells sent smooth, straight, lateral processes
      that bent and became beaded as they passed ventrally and crossed to the
      contralateral side of the cord. There, the processes of several cells aggregated
      to give rise to a longitudinal fiber bundle. Beaded collaterals of these
      processes were directed to ventral neuropil and did not appear to contact giant
      Rohde cell axons. The crossed projections of the Hesse photoreceptors are
      compared with those of vertebrate retinal ganglion cells. Other antisera raised
      against GnRH weakly labeled rhabdomeric photoreceptors located dorsally in the
      brain, the Joseph cells. The finding that GnRH antibodies label amphioxus
      photoreceptor cells and axons is not definitive proof that the photoreceptors
      contain GnRH. Regardless of whether the antibody recognizes amphioxus GnRH, which
      has not yet been identified by structure, the antibody has revealed the processes
      of the Hesse photoreceptor cells.

PMID- 16304680
TI  - Distribution and chemical coding of corticotropin-releasing factor-immunoreactive
      neurons in the guinea pig enteric nervous system.
AB  - Immunofluorescence was used to study immunoreactivity (IR) for corticotropin
      releasing factor (CRF) in the guinea pig enteric nervous system. CRF-IR was
      expressed in both the myenteric and the submucosal plexuses of all regions of the
      large and small intestine and the myenteric plexus of the stomach. CRF-IR nerve
      fibers were present in the myenteric and submucosal plexuses, in the circular
      muscle coat, and surrounding submucosal arterioles. Most of the CRF-IR fibers
      persisted in the myenteric and submucosal plexuses after 7 days in organotypic
      culture. CRF-IR was not coexpressed with tyrosine hydroxylase-IR or calcitonin
      gene-related peptide-IR fibers. The proportions of CRF-IR cell bodies in the
      myenteric plexus increased progressively from the stomach (0.6%) to the distal
      colon (2.8%). Most of the CRF-IR myenteric neurons (95%) had uniaxonal
      morphology; the remainder had Dogiel type II multipolar morphology. CRF-IR cell
      bodies in the myenteric plexus of the ileum expressed IR for choline
      acetyltransferase (56.9%), substance P (55.0%), and nitric oxide synthase
      (37.9%). CRF-IR never colocalized with IR for calbindin, calretinin, neuropeptide
      Y, serotonin, or somatostatin in the myenteric plexus. CRF-IR cell bodies were
      more abundant in the submucosal plexus (29.9-38.0%) than in the myenteric plexus.
      All CRF-IR neurons in submucosal ganglia expressed vasoactive intestinal peptide
      IR and were likely to be secretomotor/vasodilator neurons. CRF-IR neurons did not
      express IR for the CRF(1) receptor. CRF(1)-IR was expressed in neuronal neighbors
      of those with CRF-IR. Collective evidence suggests that VIPergic secretomotor
      neurons might provide synaptic input to neighboring cholinergic neurons.

PMID- 16304681
TI  - Projections from bed nuclei of the stria terminalis, dorsomedial nucleus:
      implications for cerebral hemisphere integration of neuroendocrine, autonomic,
      and drinking responses.
AB  - The overall projection pattern of a tiny bed nuclei of the stria terminalis
      anteromedial group differentiation, the dorsomedial nucleus (BSTdm), was analyzed
      with the Phaseolus vulgaris-leucoagglutinin anterograde pathway tracing method in
      rats. Many brain regions receive a relatively moderate to strong input from the
      BSTdm. They fall into eight general categories: humeral sensory-related
      (subfornical organ and median preoptic nucleus, involved in initiating drinking
      behavior and salt appetite), neuroendocrine system (magnocellular: oxytocin,
      vasopressin; parvicellular: gonadotropin-releasing hormone, somatostatin,
      thyrotropin-releasing hormone, corticotropin-releasing hormone), central
      autonomic control network (central amygdalar nucleus, BST anterolateral group,
      descending paraventricular hypothalamic nucleus, retrochiasmatic area,
      ventrolateral periaqueductal gray, Barrington's nucleus), hypothalamic
      visceromotor pattern-generator network (five of six known components), behavior
      control column (ingestive: descending paraventricular nucleus; reproductive:
      lateral medial preoptic nucleus; defensive: anterior hypothalamic nucleus;
      foraging: ventral tegmental area, along with interconnected nucleus accumbens and
      substantia innominata), orofacial motor control (retrorubral area),
      thalamocortical feedback loops (paraventricular, central medial,
      intermediodorsal, and medial mediodorsal nuclei; nucleus reuniens), and
      behavioral state control (subparaventricular zone, ventrolateral preoptic
      nucleus, tuberomammillary nucleus, supramammillary nucleus, lateral habenula, and
      raphe nuclei). This pattern of axonal projections, and what little is known of
      its inputs suggest that the BSTdm is part of a striatopallidal differentiation
      involved in coordinating the homeostatic and behavioral responses associated
      thirst and salt appetite, although clearly it may relate them to other functions
      as well. The BSTdm generates the densest known inputs directly to the
      neuroendocrine system from any part of the cerebral hemispheres.

PMID- 16304683
TI  - Columnar projections from the cholinergic nucleus isthmi to the optic tectum in
      chicks (Gallus gallus): a possible substrate for synchronizing tectal channels.
AB  - The cholinergic division of the avian nucleus isthmi, the homolog of the
      mammalian nucleus parabigeminalis, is composed of the pars parvocellularis (Ipc)
      and pars semilunaris (SLu). Ipc and SLu were studied with in vivo and in vitro
      tracing and intracellular filling methods. 1) Both nuclei have reciprocal
      homotopic connections with the ipsilateral optic tectum. The SLu connection is
      more diffuse than that of Ipc. 2) Tectal inputs to Ipc and SLu are Brn3a
      immunoreactive neurons in the inner sublayer of layer 10. Tectal neurons
      projecting on Ipc possess "shepherd's crook" axons and radial dendritic fields in
      layers 2-13. 3) Neurons in the mid-portion of Ipc possess a columnar spiny
      dendritic field. SLu neurons have a large, nonoriented spiny dendritic field. 4)
      Ipc terminals form a cylindrical brush-like arborization (35-50 microm wide) in
      layers 2-10, with extremely dense boutons in layers 3-6, and a diffuse
      arborization in layers 11-13. SLu neurons terminate in a wider column (120-180
      microm wide) lacking the dust-like boutonal features of Ipc and extend in layers
      4c-13 with dense arborizations in layers 4c, 6, and 9-13. 5) Ipc and SLu contain
      specialized fast potassium ion channels. We propose that dense arborizations of
      Ipc axons may be directed to the distal dendritic bottlebrushes of motion
      detecting tectal ganglion cells (TGCs). They may provide synchronous activation
      of a group of adjacent bottlebrushes of different TGCs of the same type via their
      intralaminar processes, and cross channel activation of different types of TGCs
      within the same column of visual space.

PMID- 16304682
TI  - Projections from bed nuclei of the stria terminalis, magnocellular nucleus:
      implications for cerebral hemisphere regulation of micturition, defecation, and
      penile erection.
AB  - The basic structural organization of axonal projections from the small but
      distinct magnocellular and ventral nuclei (of the bed nuclei of the stria
      terminalis) was analyzed with the Phaseolus vulgaris leucoagglutinin anterograde
      tract tracing method in adult male rats. The former's overall projection pattern
      is complex, with over 80 distinct terminal fields ipsilateral to injection sites.
      Innervated regions in the cerebral hemisphere and brainstem fall into nine
      general functional categories: cerebral nuclei, behavior control column,
      orofacial motor-related, humorosensory/thirst-related, brainstem autonomic
      control network, neuroendocrine, hypothalamic visceromotor pattern-generator
      network, thalamocortical feedback loops, and behavioral state control. The most
      novel findings indicate that the magnocellular nucleus projects to virtually all
      known major parts of the brain network that controls pelvic functions, including
      micturition, defecation, and penile erection, as well as to brain networks
      controlling nutrient and body water homeostasis. This and other evidence suggests
      that the magnocellular nucleus is part of a corticostriatopallidal
      differentiation modulating and coordinating pelvic functions with the maintenance
      of nutrient and body water homeostasis. Projections of the ventral nucleus are a
      subset of those generated by the magnocellular nucleus, with the obvious
      difference that the ventral nucleus does not project detectably to Barrington's
      nucleus, the subfornical organ, the median preoptic and parastrial nuclei, the
      neuroendocrine system, and midbrain orofacial motor-related regions.

PMID- 16304684
TI  - Afferent projections to the pontine micturition center in the cat.
AB  - The pontine micturition center (PMC) or Barrington's nucleus controls micturition
      by way of its descending projections to the sacral spinal cord. However, little
      is known about the afferents to the PMC that control its function and may be
      responsible for dysfunction in patients with urge-incontinence and overactive
      bladder. In five female cats, wheatgerm agglutinin-conjugated horseradish
      peroxidase (WGA-HRP) injections were made in the PMC and adjoining dorsolateral
      pontine tegmentum. Retrogradely labeled neurons were found in a large area,
      including the medullary and pontine medial and lateral tegmental field;
      dorsomedial, lateral, and ventrolateral periaqueductal gray matter (PAG);
      posterior hypothalamus; medial preoptic area (MPO); bed nucleus of the stria
      terminalis; central nucleus of the amygdala; and infralimbic, prelimbic, and
      insular cortices. To verify whether these areas indeed project specifically to
      the PMC or perhaps only to adjacent structures in the pontine tegmentum, in 67
      cats (3)H-leucine or WGA-HRP injections were made in each of these regions. Five
      cell groups appeared to have direct connections to the PMC, the ventromedial
      pontomedullary tegmental field, the ventrolateral and dorsomedial PAG, the MPO,
      and the posterior hypothalamus. The possible functions of these projections are
      discussed. These results indicate that all other parts of the brain that
      influence micturition have no direct connection with the PMC.

PMID- 16304685
TI  - Projections from bed nuclei of the stria terminalis, anteromedial area: cerebral
      hemisphere integration of neuroendocrine, autonomic, and behavioral aspects of
      energy balance.
AB  - The anteromedial area of the bed nuclei of the stria terminalis (BSTam) is the
      relatively undifferentiated region of the anterior medial (anteromedial) group of
      the bed nuclei of the stria terminalis (BSTamg), which also includes the more
      distinct dorsomedial, magnocellular, and ventral nuclei. The overall pattern of
      axonal projections from the rat BSTam was analyzed with the Phaseolus vulgaris
      leucoagglutinin anterograde pathway tracing method. Brain areas receiving
      relatively moderate to strong inputs from the BSTam fall into five general
      categories: neuroendocrine system (regions containing pools of magnocellular
      oxytocin neurons, and parvicellular corticotropin-releasing hormone, thyrotropin
      releasing hormone, somatostatin, and dopamine neurons); central autonomic control
      network (central amygdalar nucleus, descending paraventricular nucleus, and
      ventrolateral periaqueductal gray); hypothalamic visceromotor pattern generator
      network (five of six known components); behavior control column (descending
      paraventricular nucleus and associated arcuate nucleus; ventral tegmental area
      and associated nucleus accumbens and substantia innominata); and behavioral state
      control (supramammillary and tuberomammillary nuclei). The BSTam projects lightly
      to thalamocortical feedback loops (via the medial-midline-intralaminar thalamus).
      Its pattern of axonal projections, combined with its pattern of neural inputs
      (the most varied of all BST cell groups), suggests that the BSTam is part of a
      striatopallidal differentiation involved in coordinating neuroendocrine,
      autonomic, and behavioral or somatic responses associated with maintaining energy
      balance homeostasis.

PMID- 16304687
TI  - Comparative study of the sources of neuronal projections to the site of
      gonadotrophin-releasing hormone perikarya and to the anteroventral
      periventricular nucleus in female rats.
AB  - The rat ovulatory cycle is dependent on the preoptic region encompassing the
      gonadotrophin-releasing hormone (GnRH) perikarya and the anteroventral
      periventricular nucleus (AVPV). Retrograde tract tracing was used to identify and
      compare the sources of inputs to these sites in female rats. Within the
      telencephalon and diencephalon, the incidence of retrograde labelling from both
      sites was moderate to abundant in the ventral lateral septum, posteromedial bed
      nucleus of the stria terminalis, amygdalohippocampal area and the
      periventricular, medial preoptic, anterodorsal preoptic, dorsomedial
      suprachiasmatic, arcuate, and posterior ventrolateral ventromedial hypothalamic
      nuclei. In these regions, the incidence of retrograde labelling was either
      greater from the AVPV than from the GnRH perikarya site or similar from both
      sites. In the medial amygdaloid, parastrial, striohypothalamic, and ventral
      premammillary nuclei, the retrograde labelling from the AVPV greatly exceeded the
      sparse incidence from the GnRH perikarya site. In contrast, retrograde labelling
      from the GnRH perikarya site predominated in the median preoptic, lateroanterior
      and dorsomedial hypothalamic nuclei, subparaventricular zone, and retrochiasmatic
      area; it was abundant in the AVPV. Caudal to the diencephalon, retrograde
      labelling from either site was sparse, except in the lateral parabrachial
      nucleus, which displayed a particularly high incidence from the GnRH perikarya
      site. Other mesencephalic regions labelled from either site included the
      periaqueductal gray and dorsal and median raphe nuclei. The most caudal labelling
      was found in the ventrolateral medulla and region of the solitary tract nucleus;
      this was almost exclusively from the GnRH perikarya site. These findings further
      elucidate the neuroanatomical connections underlying the control of the ovulatory
      cycle.

PMID- 16304686
TI  - Changes in glycine immunoreactivity in the rat superior olivary complex following
      deafness.
AB  - The balance between inhibitory and excitatory amino acid neurotransmitters
      contributes to the control of normal functioning of the auditory brainstem.
      Changes in the level of neuronal activity within the auditory brainstem pathways
      influence the balance between inhibition and excitation. Activity-dependent
      plasticity in the auditory pathways can be studied by creating a large decrease
      in activity through peripheral deafening. Deafness-related decreases in GABA have
      previously been shown in the inferior colliculus. However, glycine is a more
      prevalent inhibitory transmitter in the mature superior olivary complex (SOC).
      The present study therefore examined if there were deafness-related changes in
      glycine in the SOC using postembedding immunocytochemistry. Animals were
      bilaterally deafened by an intrascalar injection of neomycin. Five nuclei in the
      SOC, the lateral superior olive (LSO), superior paraolivary nucleus (SPoN), and
      the medial, lateral, and ventral nuclei of the trapezoid body (MNTB, LNTB, and
      VNTB) were examined 14 days following the deafening and compared to normal
      hearing age-matched controls. The LSO and SPoN were divided into high and low
      frequency regions. The number of glycine immunoreactive puncta on the somata of
      principal cells showed significant decreases in all regions assessed, with
      changes ranging from 50% in the VNTB to 23% in the LSO.

PMID- 16304688
TI  - Effects of radiofrequency radiation emitted by cellular telephones on the
      cognitive functions of humans.
AB  - The present study examined the effects of exposure to Electromagnetic Radiation
      emitted by a standard GSM phone at 890 MHz on human cognitive functions. This
      study attempted to establish a connection between the exposure of a specific area
      of the brain and the cognitive functions associated with that area. A total of 36
      healthy right-handed male subjects performed four distinct cognitive tasks:
      spatial item recognition, verbal item recognition, and two spatial compatibility
      tasks. Tasks were chosen according to the brain side they are assumed to
      activate. All subjects performed the tasks under three exposure conditions: right
      side, left side, and sham exposure. The phones were controlled by a base station
      simulator and operated at their full power. We have recorded the reaction times
      (RTs) and accuracy of the responses. The experiments consisted of two sections,
      of 1 h each, with a 5 min break in between. The tasks and the exposure regimes
      were counterbalanced. The results indicated that the exposure of the left side of
      the brain slows down the left-hand response time, in the second-later-part of the
      experiment. This effect was apparent in three of the four tasks, and was highly
      significant in only one of the tests. The exposure intensity and its duration
      exceeded the common exposure of cellular phone users.

PMID- 16304689
TI  - Therapeutic staff exposure to magnetic field pulses during TMS/rTMS treatments.
AB  - Transcranial magnetic stimulation or repetitive transcranial magnetic stimulation
      (TMS/rTMS) is currently being used in treatments of the central nervous system
      diseases, for instance, depressive states. The principles of localized magnetic
      stimulation are summarized and the risk and level of occupational field exposure
      of the therapeutic staff is analyzed with reference to ICNIRP guidelines for
      pulses below 100 kHz. Measurements and analysis of the occupational exposure to
      magnetic fields of the staff working with TMS/rTMS are presented.

PMID- 16304690
TI  - Personal dosimetry of exposure to mobile telephone base stations? An
      epidemiologic feasibility study comparing the Maschek dosimeter prototype and the
      Antennessa SP-090 system.
AB  - The aim of our study was to test the feasibility and reliability of personal
      dosimetry. Twenty-four hour exposure assessment was carried out in 42 children,
      57 adolescents, and 64 adults using the Maschek dosimeter prototype. Self
      reported exposure to mobile phone frequencies were compared with the dosimetry
      results. In addition, dosimetry readings of the Maschek device and those of the
      Antennessa DSP-090 were compared in 40 subjects. Self-reported exposures were not
      associated with dosimetry readings. The measurement results of the two dosimeters
      were in moderate agreement (r(Spearman) = 0.35; P = .03). Personal dosimetry for
      exposure to mobile phone base station might be feasible in epidemiologic studies.
      However, the consistency seems to be moderate.

PMID- 16304691
TI  - Comment on "Scaling the thermophysiological effects of radiofrequency radiation-
      revisited".

PMID- 16304693
TI  - Effects of pulsed magnetic stimulation on tumor development and immune functions
      in mice.
AB  - We investigated the effects of pulsed magnetic stimulation on tumor development
      processes and immune functions in mice. A circular coil (inner diameter = 15 mm,
      outer diameter = 75 mm) was used in the experiments. Stimulus conditions were
      pulse width = 238 micros, peak magnetic field = 0.25 T (at the center of the
      coil), frequency = 25 pulses/s, 1,000 pulses/sample/day and magnetically induced
      eddy currents in mice = 0.79-1.54 A/m(2). In an animal study, B16-BL6 melanoma
      model mice were exposed to the pulsed magnetic stimulation for 16 days from the
      day of injection of cancer cells. A tumor growth study revealed a significant
      tumor weight decrease in the stimulated group (54% of the sham group). In a
      cellular study, B16-BL6 cells were also exposed to the magnetic field (1,000
      pulses/sample, and eddy currents at the bottom of the dish = 2.36-2.90 A/m(2));
      however, the magnetically induced eddy currents had no effect on cell
      viabilities. Cytokine production in mouse spleens was measured to analyze the
      immunomodulatory effect after the pulsed magnetic stimulation. tumor necrosis
      factor (TNF-alpha) production in mouse spleens was significantly activated after
      the exposure of the stimulus condition described above. These results showed the
      first evidence of the anti-tumor effect and immunomodulatory effects brought
      about by the application of repetitive magnetic stimulation and also suggested
      the possible relationship between anti-tumor effects and the increase of TNF
      alpha levels caused by pulsed magnetic stimulation.

PMID- 16304694
TI  - Effects of 0.4 T rotating magnetic field exposure on density, strength, calcium
      and metabolism of rat thigh bones.
AB  - The current study investigated the effects of 0.4 T rotary non-uniform magnetic
      field (RMF) exposure on bone density in ovariectomized (OVX) rats. Results showed
      that many bone indexes are significantly elevated after RMF exposure compared to
      the control OVX group and confirmed mechanistic evidence that strong magnetic
      field (MF) exposure could effectively increase bone density and might be used to
      treat osteoporosis. Synergy of daily RMF exposure (30 min a day for 30 days using
      an 8 Hz rotary 0.4 T MF) with calcium supplement tended to increase the indexes
      of thigh bone density, energy absorption, maximum load, maximum flexibility, and
      elastic deformation as compared to those of untreated OVX control group. Results
      also revealed that the indexes of alkaline phosphatase (ALP), serum phosphate,
      and serum calcium were higher in rats exposed to RMF with calcium than in the
      untreated OVX control group. Changes in bone mineral density (BMD) and bone
      mineral content (BMC) were observed in rats for three months including the first
      month RMF exposure. Bone density in rats exposed each day for 60 min increased
      during 1-month exposure and continued to increase during the post-exposure
      period. Furthermore, bone density and calcium content in rats exposed for 90 min
      daily decreased initially in the exposure month; however, ratio of increase was
      well above the control values by the end of the post-exposure period suggesting
      possible window and delayed effects. The study indicated that RMF exposure to
      both male and OVX female rats for 120 min a day over 15 day period should
      effectively promote increase of bone calcium contents (BCC) and bone-specific
      alkaline phosphatase (BAP) in rats thigh bone as well as a corresponding decrease
      in deoxypyridinoline crosslinks (DPD).

PMID- 16304695
TI  - Magnetic field exposure stiffens regenerating plant protoplast cell walls.
AB  - Single suspension-cultured plant cells (Catharanthus roseus) and their
      protoplasts were anchored to a glass plate and exposed to a magnetic field of 302
      +/- 8 mT for several hours. Compression forces required to produce constant cell
      deformation were measured parallel to the magnetic field by means of a cantilever
      type force sensor. Exposure of intact cells to the magnetic field did not result
      in any changes within experimental error, while exposure of regenerating
      protoplasts significantly increased the measured forces and stiffened
      regenerating protoplasts. The diameters of intact cells or regenerating
      protoplasts were not changed after exposure to the magnetic field. Measured
      forces for regenerating protoplasts with and without exposure to the magnetic
      field increased linearly with incubation time, with these forces being divided
      into components based on the elasticity of synthesized cell walls and cytoplasm.
      Cell wall synthesis was also measured using a cell wall-specific fluorescent dye,
      and no changes were noted after exposure to the magnetic field. Analysis
      suggested that exposure to the magnetic field roughly tripled the Young's modulus
      of the newly synthesized cell wall without any lag.

PMID- 16304696
TI  - Do ambient electromagnetic fields affect behaviour? A demonstration of the
      relationship between geomagnetic storm activity and suicide.
AB  - The relationship between ambient electromagnetic fields and human mood and
      behaviour is of great public health interest. The relationship between Ap indices
      of geomagnetic storm activity and national suicide statistics for Australia from
      1968 to 2002 was studied. Ap index data was normalised so as to be globally
      uniform and gave a measure of storm activity for each day. A geomagnetic storm
      event was defined as a day in which the Ap index was equal to or exceeded 100 nT.
      Suicide data was a national tally of daily male and female death figures where
      suicide had been documented as the cause of death. A total of 51 845 males and 16
      327 females were included. The average number of suicides was greatest in spring
      for males and females, and lowest in autumn for males and summer for females.
      Suicide amongst females increased significantly in autumn during concurrent
      periods of geomagnetic storm activity (P = .01). This pattern was not observed in
      males (P = .16). This suggests that perturbations in ambient electromagnetic
      field activity impact behaviour in a clinically meaningful manner. The study
      furthermore raises issues regarding other sources of stray electromagnetic fields
      and their effect on mental health.

PMID- 16304697
TI  - Nanosecond pulsed electric field generators for the study of subcellular effects.
AB  - Modeling and experimental studies have shown that pulsed electric fields of
      nanosecond duration and megavolt per meter amplitude affect subcellular
      structures but do not lead to the formation of large pores in the outer membrane.
      This "intracellular electromanipulation" requires the use of pulse generators
      which provide extremely high power but low energy pulses. In this study, we
      describe the concept of the required pulsed power sources, their design,
      operation, and the necessary diagnostics. Two types of pulse generators based on
      the Blumlein line principle have been developed and are described here. One
      system is designed to treat a large number of cells in cuvettes holding volumes
      from 0.1 to 0.8 ml. Pulses of up to 40 kV amplitude, with a duration of 10 ns and
      a rise time close to 1 ns can be applied to the cuvette. For an electrode gap of
      1 mm this voltage corresponds to an average electric field of 40 MV/m. The second
      system allows for real time observation of individual cells under a microscope.
      It generates pulses of 10-300 ns duration with a rise time of 3.5 ns and voltage
      amplitudes up to 1 kV. Connected to a microreactor with an electrode gap of 100
      microm, electric fields up to 10 MV/m are applied.

PMID- 16304698
TI  - A 50 Hz sinusoidal magnetic field does not damage MG-63 three-dimensional tumor
      spheroids but induces changes in their invasive properties.
AB  - The possibility that a sinusoidal 50 Hz magnetic field with a magnetic flux
      density of 1 mT can damage MG-63 osteosarcoma spheroids and induce variations in
      the invasive properties of these three-dimensional model systems after 2 days of
      exposure was investigated. Specifically, possible damage induced by these fields
      was examined by determining changes in spheroid surface morphology (light
      microscopy), growth (spheroid diameter and protein content determination),
      lactate dehydrogenase release, and reduced glutathione amount. Possible changes
      in the invasive properties were studied by invasion chambers. The results show no
      induction of cell damage by ELF fields while invasion chamber assays demonstrate
      a significant increase in the invasive potential of exposed spheroids. In order
      to determine if the fibronectin or hyaluronan receptors are involved, Western
      blot analysis was conducted on these two proteins. No significant variations were
      observed in either receptor in MG-63 multicellular tumor spheroids.

PMID- 16304699
TI  - Psychophysiological tests and provocation of subjects with mobile phone related
      symptoms.
AB  - The aim of the present study was to investigate the effect of exposure to a
      mobile phone-like radiofrequency (RF) electromagnetic field on persons
      experiencing subjective symptoms when using mobile phones (MP). Twenty subjects
      with MP-related symptoms were recruited and matched with 20 controls without MP
      related symptoms. Each subject participated in two experimental sessions, one
      with true exposure and one with sham exposure, in random order. In the true
      exposure condition, the test subjects were exposed for 30 min to an RF field
      generating a maximum SAR(1g) in the head of 1 W/kg through an indoor base station
      antenna attached to a 900 MHz GSM MP. The following physiological and cognitive
      parameters were measured during the experiment: heart rate and heart rate
      variability (HRV), respiration, local blood flow, electrodermal activity,
      critical flicker fusion threshold (CFFT), short-term memory, and reaction time.
      No significant differences related to RF exposure conditions were detected. Also
      no differences in baseline data were found between subject groups, except for the
      reaction time, which was significantly longer among the cases than among the
      controls the first time the test was performed. This difference disappeared when
      the test was repeated. However, the cases differed significantly from the
      controls with respect to HRV as measured in the frequency domain. The cases
      displayed a shift in low/high frequency ratio towards a sympathetic dominance in
      the autonomous nervous system during the CFFT and memory tests, regardless of
      exposure condition. This might be interpreted as a sign of differences in the
      autonomous nervous system regulation between persons with MP related subjective
      symptoms and persons with no such symptoms.

PMID- 16304700
TI  - Influence of 50 Hz magnetic field on sex hormones and other fertility parameters
      of adult male rats.
AB  - The effects of an extremely low frequency (ELF) magnetic field on the sex
      hormones and other fertility parameters of adult male Sprague-Dawley rats were
      investigated. Adult male rats were exposed to a 50 Hz sinusoidal magnetic field
      at approximately 25 microT (rms) for 18 consecutive weeks. There were no
      significant effects on the absolute body weight and the weight of the testes of
      the exposed rats. However, the weights of seminal vesicles and preputial glands
      were significantly reduced in the exposed male rats. Similarly, a significant
      reduction in sperm count was observed in the exposed group. Furthermore, there
      were no significant effects on the serum levels of male follicle stimulating
      hormone (FSH) during the 18 weeks of exposure period. On the other hand, there
      was a significant increase in the serum levels of male luteinizing hormone (LH)
      after 18 weeks of exposure (P < .005), while testosterone levels were
      significantly decreased only after 6 and 12 weeks of the exposure period. These
      results suggest that long term exposure to ELF could have adverse effects on
      mammalian fertility and reproduction.

PMID- 16304701
TI  - Does acute exposure to mobile phones affect human attention?
AB  - Recent studies have indicated that acute exposure to low level radiofrequency
      (RF) electromagnetic fields generated by mobile phones affects human cognition.
      However, the relatively small samples used, in addition to methodological
      problems, make the outcomes of these studies difficult to interpret. In our study
      we tested a large sample of volunteers (168) using a series of cognitive tasks
      apparently sensitive to RF exposure (a simple reaction task, a vigilance task,
      and a subtraction task). Participants performed those tasks twice, in two
      different sessions. In one session they were exposed to RFs, with half of
      subjects exposed to GSM signals and the other half exposed to CW signals, while
      in the other session they were exposed to sham signals. No significant effects of
      RF exposure on performance for either GSM or CW were found, independent of
      whether the phone was positioned on the left or on the right side.

PMID- 16304703
TI  - Decolorization of diazo-dye Reactive Blue 172 by Pseudomonas aeruginosa NBAR12.
AB  - A novel bacterial strain capable of decolorizing textile dyes was isolated from
      dye contaminated soil obtained from industrial estate of Ahmedabad, Gujarat,
      India. The bacterial isolate Pseudomonas aeruginosa NBAR12 was capable of
      decolorizing 12 different dyes tested with decolorization efficiency varying in
      the range of 80 to 95%. Maximum extent as well as rate of Reactive Blue 172 (RB
      172) decolorization was observed when glucose (2 g x l(-1)) and yeast extract
      (2.5 g x l(-1)) were supplemented in the medium. The optimum dye pH and
      temperature for dye decolorization was found to be 7 and 40 degrees C,
      respectively. The decolorizing activity was found to increase with increasing the
      dye concentration from 50 to 400 mg x l(-1). The dye decolorization was strongly
      inhibited at 500 mg dye l(-1) in the medium. High performance thin layer
      chromatography analysis indicated that dye decolorization occurred due to the
      breakdown of dye molecules into colorless end products.

PMID- 16304702
TI  - Lack of direct DNA damage in human blood leukocytes and lymphocytes after in
      vitro exposure to high power microwave pulses.
AB  - Currently, the potential genotoxicity of high power microwave pulses (HPMP) is
      not clear. Using the alkaline single cell gel electrophoresis assay, also known
      as the alkaline comet assay, we studied the effects of HPMP (8.8 GHz, 180 ns
      pulse width, peak power 65 kW, pulse repetition frequency 50 Hz) on DNA of human
      whole-blood leukocytes and isolated lymphocytes. The cell suspensions were
      exposed to HPMP for 40 min in a rectangular waveguide. The average SAR calculated
      from the temperature kinetics was about 1.6 kW/kg (peak SAR was about 300 MW/kg).
      The steady-state temperature rise in the 50 microl samples exposed to HPMP was
      3.5 +/- 0.1 degrees C. In independent experiments, we did not find any
      statistically significant DNA damage manifested immediately after in vitro HPMP
      exposure of human blood leukocytes or lymphocytes or after HPMP exposure of
      leukocytes subsequently incubated at 37 degrees C for 30 min. Our results
      indicate that HPMP under the given exposure conditions did not induce DNA strand
      breaks, alkali-labile sites, and incomplete excision repair sites, which could be
      detected by the alkaline comet assay.

PMID- 16304704
TI  - Growth of Enterococcus mundtii ST15 in medium filtrate and purification of
      bacteriocin ST15 by cation-exchange chromatography.
AB  - Bacteriocin ST15 (bacST15), produced by Enterococcus mundtii ST15, inhibited the
      growth of a variety of bacteria, including exopolysaccharide (EPS)-producing
      strains isolated from biofilms in stainless steel pipes. Maximal production of
      bacST15 (51200 AU/ml) was recorded after 20 h of growth in MRS broth (Biolab),
      which was maintained throughout fermentation. Only 12800 AU/ml bacST15 has been
      recorded in MRS filtrate with components smaller than 8000 Da, suggesting that
      nutrients larger than 8000 Da are required for optimal bacST15 production. Cation
      exchange chromatography yielded an active peptide, which is 3944.00 Da, according
      to electron-spray mass spectrometry and tricin-SDS PAGE. BacST15 is smaller than
      the 4287 Da reported for bacteriocins ATO6 and KS produced by E. mundtii . The
      iso-electric point of bacST15 is between 7 and 9, and similar to that reported
      for pediocin PD-1.

PMID- 16304705
TI  - Activity of Serratia plymuthica IC1270 gene chiA promoter region in Escherichia
      coli mutants deficient in global regulators of transcription.
AB  - To study the regulation of expression of the Serratia plymuthica gene chiA
      encoding a 58-kDa endochitinase, its 586-bp-long upstream regulatory region was
      cloned, sequenced and fused to a promoterless lac operon in phage lambdaRS45 to
      obtain a single-copy transcriptional fusion (P F1chiA )-lac in lysogens of
      Escherichia coli wild-type strains or their mutants deficient in various global
      regulators of transcription. The level of P F1chiA -lac expression increased
      about 20- and 90-fold, respectively, in E. coli K12 Deltahns and double Deltahns
      stpA mutants deficient in H-NS, and in both H-NS and StpA DNA-binding histone
      like proteins, as compared to levels in the wild-type strain. In a Deltalrp
      mutant deficient in the leucine-responsive transcriptional regulator Lrp, the
      level of P F1chiA -lac expression increased only up to threefold, whereas even
      smaller differences relative to the wild-type strain were observed in rpoS and
      Deltacrp mutants deficient in the sigmaS subunit of RNA polymerase and catabolite
      repression protein (CRP), respectively. Deletion of the inverted-repeat sequences
      and curved DNA regions located in the upstream region of chiA essentially did not
      influence strain IC1270's chiA promoter activity in E. coli .

PMID- 16304706
TI  - Persistence of two Rhizobium etli inoculant strains in clay and silty loam soils.
AB  - The persistence of Rhizobium etli strains CE3 and Ph 163 was studied in two soil
      types representing major French bean growing areas in Egypt. Clay soil from
      MENOUFIA and silty loam soil from ISMAILIA were planted by bean Cultivars; Bronco
      and Giza 6. The inoculation with strain Ph 163 in the first bean cultivation was
      significantly higher in nodule biomass and number; whereas, the strain CE3 was
      significantly higher in plant biomass accumulation (Moawad et al. 2004). The
      persisting inocula strains seem to perform differently in the two soils in terms
      of nodulation, biomass accumulation and N-uptake by the two cultivars as compared
      with their performance with the first inoculation. CE3 strain persisting in the
      soil performed better than Ph.163 strain. The nodule occupancy by the persisting
      inoculant rhizobial was determined by two approaches; fluorescent antibody (FA)
      technique and other Rep-PCR fingerprinting. Both techniques were close in the
      evaluation of persisting inoculant strains which nodulated beans in the second
      planting season without inoculation. The results obtained showed that both
      strains are good survivors in the two soils.

PMID- 16304707
TI  - Characterization and screening of bacteria from rhizosphere of maize grown in
      Indonesian and Pakistani soils.
AB  - Thirty rhizobacteria isolated from maize grown in Pakistani and Indonesian soils
      were evaluated for their morphological characteristics, nitrogen fixation, P
      solubilization, indole acetic acid (IAA) and siderophores production. Nitrogenase
      activity was detected in nineteen isolates ranging from 21.8-3624 n moles C2H4
      produced/h/mg protein. Most of the isolates produced IAA, ten were capable of
      siderophore production while four were P-solubilizers. Ultrastructural studies of
      Pseudomonas sp. F14 indicated characteristic rhizospheric colonization within 48
      h that was observed to change considerably with the passage of time from few
      bacteria to micro colonies. Random amplified polymorphic DNA (RAPD) analysis of
      30 bacterial strains using 30 oligonucleotide primers resulted in considerable
      level of genetic diversity, with genetic distance ranging from 2-16%. Indonesian
      isolates were found to be more diverse as compared to Pakistani isolates. The
      characterization and screening of rhizobacteria of maize rhizosphere has helped
      in selection of isolates F7, LS-1, 3.1.1.C, F2, F3 and F13 as superior strains
      for use as bioinoculant. Moreover isolate F14 identified, as Pseudomonas fulgida
      by partial 16S rRNA sequence analysis is a novel strain regarding its tremendous
      potentials for inoculum production to enhance the yield of maize.

PMID- 16304708
TI  - Growth and production of laccases by the ligninolytic fungi, Pleurotus ostreatus
      and Botryosphaeria rhodina , cultured on basal medium containing the herbicide,
      Scepter (imazaquin).
AB  - The herbicide, Scepter, whose active principle is imazaquin, is commonly used in
      soybean farming to combat wide-leaf weeds. The basidiomycete, Pleurotus ostreatus
      , and the ascomycete, Botryosphaeria rhodina , were evaluated for their growth
      and laccase production when cultured on basal media containing Scepter. Both
      fungi could grow on the herbicide when cultivated in solid and submerged liquid
      culture in the presence of Scepter at concentrations of 0-6% (v/v) for P.
      ostreatus , and up to 0-50% (v/v) for B. rhodina , and in each case produced
      laccases when assayed against ABTS [2,2(1)-azino-bis(3-ethylbenzthiazoline-6
      sulfonic acid)] and 2,6-dimethoxyphenol. P . ostreatus could tolerate up to 6% of
      Scepter before it became toxic to the fungus, while in the case of B. rhodina ,
      50% (v/v) Scepter was the highest amount that supported grow, and laccase
      activity was detectable up to 25% (v/v). An inverse relationship existed between
      the level of Scepter in the culture medium that supported fungal growth and
      laccase production. Analysis of the results showed that the fungi studied
      presented different behaviour towards Scepter in the culture environment.

PMID- 16304709
TI  - Bleaching of Serratia marcescens by some coumarins: a spectrophotometric study.
AB  - Recently, we reported that umbelliprenin inhibits the red pigment production in
      Serratia marcescens . In this current investigation the bleaching effect of the
      umbelliprenin was further studied using the spectrophotometric method, and its IC
      50 was calculated. Also in this study the effect of the other coumarins extracted
      from Ferula persica roots were evaluated for depigmentation of Serratia
      marcescens . None of these compounds appeared to have a bleaching effect against
      a test strain at certain concentrations. Comparing the structures of the
      different coumarins showed that the linear sesquiterpene part of the
      umbelliprenin structure may be essential for the bleaching effect of S.
      marcescens .

PMID- 16304710
TI  - Simulation of biofilm formation at different assimilable organic carbon
      concentrations under lower flow velocity condition.
AB  - A simulation model was established in this study to evaluate the impacts of
      assimilable organic carbon concentration on the growth of biofilm and bulk
      bacteria under lower flow velocity conditions. The experimental results showed
      that the growth trends of heterotrophic plate count bacteria of biofilm and bulk
      bacteria were coincident with the pattern of logistic growth model. The effects
      of the assimilable organic carbon level on the (specific) growth rates of biofilm
      and bulk bacteria were quite significant, and the higher the assimilable organic
      carbon level was, the higher the (specific) growth rate was. There was a growth
      and decline relationship between the maximum quantities of biofilm and bulk water
      bacteria at steady state. The maximum growth rate of biofilm bacteria
      exponentially increased with the increase of assimilable organic carbon level.
      The length of time that the maximum growth rate occurred was inversely decreased
      with the increase of assimilable organic carbon level. Some results of this study
      support the inference that the increase of bulk bacteria results mainly from the
      release or detachment of biofilm bacteria, not from the growth itself.

PMID- 16304712
TI  - Underrecognition of the severity of asthma and undertreatment of asthma in a
      rural area of Japan.
AB  - BACKGROUND AND AIM: Revised guidelines were released in Japan in 2003 for the
      assessment, treatment, and management of adult asthmatics, and similar guidelines
      for child asthmatics were released in 2002. We reassessed the severity and
      possible undertreatment of asthma according to these guidelines in stable
      asthmatics. METHODS: We reviewed medical records of 861 well-controlled asthmatic
      patients who, in April through June 2004 were cared for by 47 pulmonologists at
      29 medical centers and 13 asthma clinics in a rural community in the San-in area
      of Japan. The physician obtained completed medical records about their symptoms
      and current treatment of the subjects, 726 adult and 135 children (aged 6 years
      or older) who were in stable condition and had had no exacerbations in the
      previous 3 months. The severity of asthma and current treatment for each patient
      were assessed according to the newly revised Japanese guidelines for the
      assessment, treatment, and management of adult and child asthmatics. RESULTS: In
      adult and child asthmatics, the percentage of predicted forced expiratory volume
      at 1 second (FEV1.0) was smaller and has a narrower distribution range than the
      percentage of predicted peak expiratory flow (PEF). When the severity of asthma
      was classified according to symptoms alone, 50% and 35% of those classified as
      mildly asthmatics patients with adults and children, respectively, had moderate
      to severe airflow limitation. Inhaled corticosteroids were prescribed to 90.6% of
      adult and 14.9% of child patients. When we compared the treatments that patients
      were actually receiving against the optimal treatments indexed according to a
      combined symptoms-FEV1.0 classification, we found that 49% of adult asthmatics
      were overtreated, 21% were properly treated, and 30% were undertreated. Among
      children, the respective percentages were 35%, 25%, and 40%. CONCLUSION: In well
      controlled adult and child asthmatics, the severity of asthma is poorly judged
      when symptoms alone are considered. We suggest that the severity of asthma should
      be assessed through a combination of symptoms and the measurement of FEV1.0
      during office visits. We also suggest that the proper dose of inhaled steroid
      needed to maintain stable conditions should be judged according to this combined
      symptoms-FEV1.0 classification.

PMID- 16304713
TI  - Heme oxygenase-1 (Hsp32) is involved in the protection of small intestine by
      whole body mild hyperthermia from ischemia/reperfusion injury in rat.
AB  - AIM: The aim of the present study was to explore whether heme oxygenase-1 (HO-1)
      is involved in the hyperthermia-provided protection of the small intestine from
      ischemia/reperfusion injury in rats. METHODS: Intestinal damage was induced in
      male Sprague-Dawley rats by clamping both the superior mesenteric artery and the
      celiac trunk for 30 min, followed by reperfusion. Whole-body hyperthermia was
      induced in anesthetized rats by placement in a temperature-controlled water bath.
      Whole-body hyperthermia to a core temperature of 42-43 degrees C for 15 min was
      followed by passive cooling. We started the hyperthermic treatment 6 h before the
      vascular clamping. The severity of the mucosal injury was evaluated by several
      biochemical markers and histological findings. Hyperthermia-induced heat-shock
      proteins were detected by Western blotting. We also investigated the effect of
      zinc protoporphyrin IX (an HO-1 inhibitor) on the protective effect of
      hyperthermia. RESULTS: The rats, which were killed after ischemia/reperfusion,
      had severe intestinal inflammation. Hyperthermia significantly induced the
      production of Hsp70 and HO-1 in intestinal mucosa and significantly reduced
      ischemia/reperfusion-induced mucosal injury. The combination of zinc
      protoporphyrin IX with hyperthermia extinguished the protective effects of
      hyperthermia on ischemia/reperfusion injury. CONCLUSION: Hyperthermia protects
      against ischemia/reperfusion injury in rat small intestine through the expression
      of heat-shock proteins, especially HO-1.

PMID- 16304714
TI  - Clinical study of recombinant adenovirus-p53 (Adp53) combined with hyperthermia
      in advanced cancer (a report of 15 cases).
AB  - The study was to evaluate the efficacy of the Adp53 combined with hyperthermia on
      advanced cancer. Fifteen patients with advanced cancer were enrolled in this
      clinical trial. Thirteen patients with recurrent tumours failed in conventional
      treatments and the two other patients with primary tumour received no treatment
      before they were enrolled. Recombinant adenovirus-p53 (Adp53) is a E1 substituted
      replication-incompetent recombinant adenovirus encoding the human wild-type p53
      (wtp53) gene. The 15 patients were intra-tumourally injected with Adp53,
      1x10(12)vp (virus particle) once a week, with a total of 4-8 times was given. The
      temperature being set hyperthermia every week 3 days after the injection of Adp53
      at 43-44 degrees C using 915 MHz microwave machine for superficial tumour for 1 h
      or at 42-43 degrees C using 41 MHz radiofrequency machine for deep-seated tumour
      for 1 h. Among the 15 patients, five concurrently were added with radiotherapy
      and three were added with cisplatin-based chemotherapy. The treatment achieved CR
      in two cases, PR in four cases, SD in eight cases and PD in one case and, after
      the treatment, tumours of two cases disappeared and seven of the other 13 cases
      (54%) had low-density area (LDA) of more than 50% on CT images in tumours. In the
      15 patients, no dose-limiting toxicity and adverse events were noted, except
      transient fever after Adp53 administration. In conclusion, Adp53 combined with
      hyperthermia was safe and effective in patients with advanced cancer and p53 gene
      therapy was potential to thermosensitize in advanced cancer.

PMID- 16304715
TI  - Clinical hyperthermia of prostate cancer using magnetic nanoparticles:
      presentation of a new interstitial technique.
AB  - The aim of this pilot study was to evaluate whether the technique of magnetic
      fluid hyperthermia can be used for minimally invasive treatment of prostate
      cancer. This paper presents the first clinical application of interstitial
      hyperthermia using magnetic nanoparticles in locally recurrent prostate cancer.
      Treatment planning was carried out using computerized tomography (CT) of the
      prostate. Based on the individual anatomy of the prostate and the estimated
      specific absorption rate (SAR) of magnetic fluids in prostatic tissue, the number
      and position of magnetic fluid depots required for sufficient heat deposition was
      calculated while rectum and urethra were spared. Nanoparticle suspensions were
      injected transperineally into the prostate under transrectal ultrasound and
      flouroscopy guidance. Treatments were delivered in the first magnetic field
      applicator for use in humans, using an alternating current magnetic field with a
      frequency of 100 kHz and variable field strength (0-18 kA m(-1)). Invasive
      thermometry of the prostate was carried out in the first and last of six weekly
      hyperthermia sessions of 60 min duration. CT-scans of the prostate were repeated
      following the first and last hyperthermia treatment to document magnetic
      nanoparticle distribution and the position of the thermometry probes in the
      prostate. Nanoparticles were retained in the prostate during the treatment
      interval of 6 weeks. Using appropriate software (AMIRA), a non-invasive
      estimation of temperature values in the prostate, based on intra-tumoural
      distribution of magnetic nanoparticles, can be performed and correlated with
      invasively measured intra-prostatic temperatures. Using a specially designed
      cooling device, treatment was well tolerated without anaesthesia. In the first
      patient treated, maximum and minimum intra-prostatic temperatures measured at a
      field strength of 4.0-5.0 kA m(-1) were 48.5 degrees C and 40.0 degrees C during
      the 1st treatment and 42.5 degrees C and 39.4 degrees C during the 6th treatment,
      respectively. These first clinical experiences prompted us to initiate a phase I
      study to evaluate feasibility, toxicity and quality of life during hyperthermia
      using magnetic nanoparticles in patients with biopsy-proven local recurrence of
      prostate cancer following radiotherapy with curative intent. To the authors'
      knowledge, this is the first report on clinical application of interstitial
      hyperthermia using magnetic nanoparticles in the treatment of human cancer.

PMID- 16304716
TI  - An uninvited dinner guest.

PMID- 16304717
TI  - Is time of the essence? The continuing search for a noninvasive measure of
      sympathetic adrenergic function.

PMID- 16304718
TI  - Abstracts from the XXI Annual Meeting of the Argentine Association of Osteology
      and Mineral Metabolism, Buenos Aires, Argentina, October 21-23, 2004.

PMID- 16304720
TI  - [Critical appraisal: band ligation and propranolol are equally effective for
      primary prevention of variceal bleeding].

PMID- 16304719
TI  - Translational research on TNF-alpha as an endogenous tumor promoter and green tea
      as cancer preventive in humans.

PMID- 16304721
TI  - [The multiple causes of relapse].

PMID- 16304722
TI  - Speckle reduction by I-divergence regularization in optical coherence tomography.
AB  - For optical coherence tomography (OCT), ultrasound, synthetic-aperture radar, and
      other coherent ranging methods, speckle can cause spurious detail that detracts
      from the utility of the image. It is a problem inherent to imaging densely
      scattering objects with limited bandwidth. Using a method of regularization by
      minimizing Csiszar's I-divergence measure, we derive a method of speckle
      minimization that produces an image that both is consistent with the known data
      and extrapolates additional detail based on constraints on the magnitude of the
      image. This method is demonstrated on a test image and on an OCT image of a
      Xenopus laevis tadpole.

PMID- 16304723
TI  - Theory and algorithms for image reconstruction on chords and within regions of
      interest.
AB  - We introduce a formula for image reconstruction on a chord of a general source
      trajectory. We subsequently develop three algorithms for exact image
      reconstruction on a chord from data acquired with the general trajectory.
      Interestingly, two of the developed algorithms can accommodate data containing
      transverse truncations. The widely used helical trajectory and other trajectories
      discussed in literature can be interpreted as special cases of the general
      trajectory, and the developed theory and algorithms are thus directly applicable
      to reconstructing images exactly from data acquired with these trajectories. For
      instance, chords on a helical trajectory are equivalent to the n-PI-line
      segments. In this situation, the proposed algorithms become the algorithms that
      we proposed previously for image reconstruction on PI-line segments. We have
      performed preliminary numerical studies, which include the study on image
      reconstruction on chords of two-circle trajectory, which is nonsmooth, and on n
      PI lines of a helical trajectory, which is smooth. Quantitative results of these
      studies verify and demonstrate the proposed theory and algorithms.

PMID- 16304724
TI  - The effects of working memory resource availability on prospective memory: a
      formal modeling approach.
AB  - The PAM theory of event-based prospective memory (Smith, 2003; Smith & Bayen,
      2004a) proposes that successful prospective memory performance demands upon the
      interaction of preparatory attentional processes and retrospective memory
      processes. The two experiments in the current study represent the first
      application of a formal model to investigate the sensitivity of these underlying
      processes to variations in working memory resource availability. Multinomial
      modeling of data from prospective-memory tasks showed that working memory span
      influenced preparatory attentional processes and retrospective-memory processes.

PMID- 16304725
TI  - The lack of pseudohomophone priming effects with short durations in reading and
      naming.
AB  - The priming effect of pseudohomophones was assessed in reading and naming tasks.
      In two experiments using the fast priming paradigm in reading, there were no
      pseudohomophone priming effects when the prime duration was 32, 44, or 56 ms from
      the beginning of a fixation. In a third experiment, using a naming task with
      isolated words, there were also no pseudohomophone priming effects with prime
      durations of 32, 44, and 56 ms, but there was with a 200-ms prime duration. The
      results suggest that pseudohomophone priming doesn't occur at an early stage of
      reading (in the first 60 ms from the beginning of fixation), but occurs at a
      later stage (within the first 200 ms).

PMID- 16304726
TI  - The metabolic syndrome: one step forward, two steps back.
AB  - Individuals with insulin resistance are at increased risk of glucose intolerance,
      dyslipidaemia and essential hypertension. In 1988, it was proposed that this
      cluster of abnormalities associated with insulin resistance identifies
      individuals at increased risk for cardiovascular disease. Recently, in an effort
      to raise awareness of this problem, both the World Health Organisation (WHO) and
      the Adult Treatment Panel III (ATP III) of the National Cholesterol Education
      Program have suggested a set of clinical criteria to diagnose individuals with
      what they both refer to as the metabolic syndrome. Although using the same term,
      the two groups have different goals for creating this diagnosis and different
      criteria to identify individuals, which relate to their different institutional
      goals. This review critically evaluates the similarities and differences between
      the two groups' concepts of the metabolic syndrome and questions the clinical
      utility of making the diagnosis with either set of definitions.

PMID- 16304727
TI  - High sensitivity, specificity and predictive value of the Connective Tissue
      Disease Screening Questionnaire among urban African-American women.
AB  - The Connective Tissue Disease Screening Questionnaire (CSQ), developed to screen
      populations for SLE and other CTDs, has been validated in a predominantly
      Caucasian population with hospital-based controls. We aimed to test the
      performance characteristics of the CSQ in an urban, predominantly African
      American population. The CSQ was administered by interview to women recruited for
      a study of environmental risk factors and SLE, including 99 cases with SLE
      validated by medical record review and 202 healthy controls recruited from the
      community. Overall, 88% of subjects had African heritage, 6% were Hispanic and 4%
      were non-Hispanic Caucasian. Controls were more likely to report African heritage
      than cases (91% versus 82%, P = 0.001). Sensitivity for detecting SLE was 88% and
      specificity was 91%. In this study, where the prevalence of SLE was 33%,
      predictive value of a positive CSQ was 82% and predictive value of a negative CSQ
      was 94%. The CSQ has slightly lower sensitivity but greater specificity for SLE
      in an urban, predominantly African-American population with community-based
      controls compared with a Caucasian population with hospital-based controls. These
      results suggest that the CSQ has adequate sensitivity and specificity and could
      be used in population studies to screen African-American women for SLE.

PMID- 16304728
TI  - Elimination of anticardiolipin antibodies and cessation of cognitive decline in a
      UV-A1-irradiated systemic lupus erythematosus patient.
AB  - In the first patient with high levels of anticardiolipin antibodies (aCL) treated
      with ultraviolet-A1 (UV-A1; 320-400 nm) radiation, eight months of twice-weekly
      low-dose (10 J/cm(2)) irradiation was accompanied by the decrease of aCL levels
      to normal, cessation of clinical and positron emission tomographic (PET) scanning
      evidence of cognitive decline, and reversal of livedo reticularis. All occurred
      within the framework of an improving Revised Systemic Lupus Activity Measure
      (SLAM-R) score. Further studies in systemic lupus erythematosus (SLE) patients
      with elevated aCL are indicated.

PMID- 16304729
TI  - Mouse B cell activation is inhibited by CD44 cross-linking.
AB  - Lymphocyte activation and trafficking are indispensable to the immune system.
      CD44 is an adhesion molecule with known importance in T cell activation,
      lymphocyte trafficking, and tumor metastasis. Although CD44 has been shown to
      participate in the activation, rolling and adhesion, and homing of T cells, the
      role of CD44 on B cells is relatively unknown. The effects of CD44 cross-linking
      on murine B cell activation via CD40L was explored using the anti-CD44 mAbs RK3G9
      and IM7. When immobilized on a plate, both RK3G9 and IM7 were found to strongly
      inhibit B cell proliferation and Ig production, especially at lower cell input
      concentrations. IgE inhibition was especially prominent. In contrast, soluble
      RK3G9 added to the B cell cultures had no effect. The inhibitory effect of anti
      CD44 on B cell activation was not influenced by the addition of the anti
      FcgammaRII, indicating that Fc cross-linking did not play a role in this
      inhibition. As Ig production requires several days for both B cell proliferation
      and differentiation to occur, the effects of delayed addition of immobilized anti
      CD44 mAbs were studied, and the results indicated no inhibition after 96 hrs of
      culture. Finally, B cells were activated by either LPS or anti-IgM F(ab')2. While
      LPS-induced B cell activation was inhibited by immobilized anti-CD44 mAbs, anti
      IgM activation was refractory. Interestingly, addition of both anti-IgM and CD40L
      or LPS resulted in some modulation of the inhibitory activity. These results
      suggest that CD44 cross-linking could control polyclonal B cell activation by
      CD40L, but allow sIgM/CD40L activation to continue.

PMID- 16304730
TI  - Enhanced antigen-specific antibody and cytokine responses when targeting antigen
      to human FcGAMMA receptor type I using an anti-human FcGAMMA receptor type I
      streptavidin fusion protein in an adjuvant-free system.
AB  - There is a continuing need for alternatives to current human adjuvants.
      Recombinant protein vaccines, which target antigen to human Fc gamma receptor
      type I (hFcgammaRI) on hFcgammaRI-expressing antigen presenting cells, provide
      one potential alternative. Using a recombinant anti-hFcgammaRI-antigen fusion
      protein and adjuvant independent mouse model, we demonstrate enhanced antigen
      specific antibody responses to low doses of antigen, when targeting antigen to
      hFcgammaRI in vivo. Enhanced antibody production to hFcyRI-targeted antigen is
      evident in both primary and secondary immune responses, as compared to that of
      non-targeted antigen. Furthermore, antibody isotype and cytokine responses
      following immunization with hFcgammaRI-targeted antigen, suggest enhancement of
      both Th1 and Th2 responses.

PMID- 16304731
TI  - A role for psychedelics in psychiatry?

PMID- 16304732
TI  - [Make an effort to improve surgical treatment for severe complications of
      gastroduodenal ulcer in China].

PMID- 16304733
TI  - Medicare program; hospice care amendments. Final rule.
AB  - This final rule revises existing regulations that govern coverage and payment for
      hospice care under the Medicare program. These revisions reflect the statutory
      changes required by the Balanced Budget Act of 1997 (BBA), the Medicare,
      Medicaid, and SCHIP Balanced Budget Refinement Act of 1999 (BBRA), and the
      Medicare, Medicaid, and SCHIP Benefits Improvement and Protection Act of 2000
      (BIPA). Additionally, these revisions reflect current policy on the documentation
      needed to support a certification of terminal illness, admission to Medicare
      hospice, and a new requirement that allows for discharges from hospice for cause
      under very limited circumstances. This final rule does not address the
      requirement for hospice data collection, the changes to the limitation of
      liability rules, or the changes to the hospice conditions of participation that
      were included in the BBA. The intent of this final rule is to expand the hospice
      benefit periods, improve documentation requirements to support certification and
      recertification of terminal illness, provide guidance on hospice admission
      procedures, clarify hospice discharge procedures, update coverage and payment
      requirements, and address the changing needs of beneficiaries, suppliers, and the
      Medicare program.

PMID- 16304735
TI  - Fair credit reporting medical information regulations. Final rules.
AB  - The OCC, Board, FDIC, OTS, and NCUA (Agencies) are publishing final rules to
      implement section 411 of the Fair and Accurate Credit Transactions Act of 2003
      (FACT Act). The final rules create exceptions to the statute's general
      prohibition on creditors obtaining or using medical information pertaining to a
      consumer in connection with any determination of the consumer's eligibility, or
      continued eligibility, for credit for all creditors. The exceptions permit
      creditors to obtain or use medical information in connection with credit
      eligibility determinations where necessary and appropriate for legitimate
      purposes, consistent with the Congressional intent to restrict the use of medical
      information for inappropriate purposes. The final rules also create limited
      exceptions to permit affiliates to share medical information with each other
      without becoming consumer reporting agencies. The final rules are substantially
      similar to the rules adopted by the Agencies on an interim final basis in June
      2005.

PMID- 16304736
TI  - Investigational new drugs: export requirements for unapproved new drug products.
      Final rule.
AB  - The Food and Drug Administration (FDA) is amending its regulations on the
      exportation of investigational new drugs, including biological products. The
      final rule describes four different mechanisms for exporting an investigational
      new drug product. These provisions implement changes in FDA's export authority
      resulting from the FDA Export Reform and Enhancement Act of 1996 and also
      simplify the existing requirements for exports of investigational new drugs.

PMID- 16304737
TI  - By the numbers. HSAs gaining momentum, new study shows.

PMID- 16304738
TI  - The contract research organization and the commercialization of scientific
      research.
AB  - The early 1980s constituted a watershed in science, mainly concerning the extent
      and nature of globalization and commercialization of scientific research, and its
      impact upon the university. Considerable debate has arisen about the sources of
      this transition, but aside from a few lone voices, the scholarly literature has
      neglected the concurrent rise of the contract research organization (CRO) and its
      role int he commercialization of scientific research. The CRO warrants wider
      attention as a modern paradigm of privatized science in the biopharmaceutical
      sector. In discussing the CRO's technologies, the purposes they pursue, and the
      legal and policy initiatives that have fostered their rapid rise, we confront the
      wider implications of the modern regime of commercialized science for the future
      conduct of scientific research. We identify five areas of innovation: treatment
      of human subjects, control of disclosure, subjection of research tools to
      commercialization, redefinition of authorship, and re-engineering the goals of
      research.

PMID- 16304739
TI  - "Yea, I have a goodly heritage": health versus heredity in the Fitter Family
      contests, 1920-1928.
AB  - By the 1920s, the future of the middle-class family had become a topic of great
      concern for mainstream Americans. This widespread concern led to a new acceptance
      of the discussion of sexual and marital issues in print and in public. Within
      this public discussion, eugenicists, physicians, clerics, sociologists, and
      various others offered solutions to the questions and concerns of their rapidly
      changing society. The Fitter Family contests, sponsored by eugenicists and held
      at state fairs in the 1920s, reflected these public and professional anxieties.
      Though infused with eugenic ideas about race betterment through better breeding,
      the contests were equally concerned with improving the health of individuals and
      strengthening American families.

PMID- 16304740
TI  - Industry influences IARC carcinogenesis evaluations.

PMID- 16304741
TI  - Promoting public health and protecting consumers in a global economy: an overview
      of HHS/FDA's international activities.

PMID- 16304742
TI  - Can the U.S. Food and Drug Administration act against global frauds? The
      extraterritorial effect of Food and Drug Administration sanctions after Small v.
      United States.

PMID- 16304743
TI  - The framework for global organic food trade circa 2005: accomplishments and
      challenges.

PMID- 16304744
TI  - The new European Community rules on the labeling of allergen ingredients in
      foodstuffs.

PMID- 16304745
TI  - Safe Food International: a blueprint for better global food safety.

PMID- 16304746
TI  - Harmonization of regulatory requirements for the development of veterinary
      clinical trials--a drive toward globalization and simplification.

PMID- 16304747
TI  - The Seventh Amendment directive--an unnecessary measure to a necessary end-
      possible legal challenges to directive 2003/15/EC of the European Parliament and
      of the Council Amending Council Directive 76/768/EEC under European Union law.

PMID- 16304748
TI  - Globalization of cosmetic regulations.

PMID- 16304749
TI  - The International Conference on Harmonization common technical document--global
      submission format?

PMID- 16304750
TI  - Global medicine does not make for global courts.

PMID- 16304751
TI  - Amendments to the Canadian Patent Act to address drug access: is help on the way?

PMID- 16304752
TI  - Brazil's AIDS controversy: antiretroviral drugs, breaking patents, and compulsory
      licensing.

PMID- 16304753
TI  - Bipolar disorders and the law.
AB  - Bipolar disorders are a neglected subject in legal scholarship. Yet they affect
      decision-making across the spectrum of the law. This editorial analyses the
      approaches adopted across a variety of areas of legal decisions. It observes a
      lack of coherence in the approach of the law and attempts to identify a number of
      issues that are posed by the diverse symptoms of the bipolar disorders. It argues
      in favour of greater judicial and tribunal member education about the disorders.

PMID- 16304754
TI  - The modern Australian law of mental harm: parochialism triumphant.

PMID- 16304755
TI  - Coroners' recommendations: a lost opportunity.

PMID- 16304756
TI  - Clinical handover: can we afford the time?

PMID- 16304757
TI  - McKenzie v Lichter.

PMID- 16304758
TI  - Harriton v Stephens; Waller v James; Waller v Hoolahan.

PMID- 16304759
TI  - Advance directives in action in a regional palliative care service: "road
      testing" the provisions of the Medical Treatment Act 1988 (VIC).
AB  - In order to explore the usefulness and acceptability of the provisions of the
      Medical Treatment Act 1988 (Vic) for palliative care patients in a rural region
      in Victoria, Australia, between July and December 2004 patients were given
      information explaining the Act and the opportunity to discuss it with the
      research officer. Grounded theory methodology was used to evaluate client
      responses. Findings suggested that palliative care patients are willing to engage
      in advance care planning but they have to be well enough and need skilled,
      practical, face-to-face assistance to complete the required legal forms. Written
      materials alone are not adequate, but provide the opportunity for medical staff
      to have conversations about death and dying. Doctors and nurses should understand
      the provisions of the Act to assist patients and families. It is recommended that
      advance care planning, appropriate to the jurisdiction, be an integral part of
      the palliative care assessment process.

PMID- 16304760
TI  - General practitioners' competence and confidentiality determinations with a minor
      who requests the oral contraceptive pill.
AB  - The right of minors to make medical treatment decisions is an issue that is not
      explicitly addressed in the legislation of most Australian jurisdictions. While
      recent common law decisions allow competent minors to consent to treatment,
      current legislation in Victoria does not provide adequate guidelines on how
      competence is to be measured. It is also unclear whether the duty of
      confidentiality is extended to competent minors. The current study explored
      general practitioners' competence and confidentiality decisions with a
      hypothetical 14-year-old patient who requests the oral contraceptive pill (OCP).
      Questionnaires were sent to 1,000 Victorian general practitioners, 305 of whom
      responded. General practitioners were asked to determine whether "Liz" was
      competent to request the OCP, and whether they would maintain her
      confidentiality. A total of 81% of respondents found the patient competent, while
      91% would have maintained her confidentiality. Results indicate that the majority
      of general practitioners used rationales that generally did not conform to
      current legal principles when making competence and confidentiality
      determinations regarding this patient.

PMID- 16304761
TI  - Will the law come running? The potential role of "brain fingerprinting" in crime
      investigation and adjudication in Australia.
AB  - A major feature of the Australian criminal justice system is that jurors assess
      witness credibility and are the ultimate finders of fact. Recognising the
      occasional fallibility of humans in detecting truth and deception, the jury's
      function may be assisted by highly regulated expert evidence about a variety of
      scientific techniques. A recent scientific development has been the invention of
      "brain fingerprinting" (BF) by Dr Larry Farwell in the United States. Brain
      fingerprinting measures brainwave functioning to detect awareness of crime
      relevant information in order to distinguish between guilty and innocent
      suspects. This article considers whether BF could be used for crime investigation
      and adjudication in Australia. By examining the rules of expert evidence and the
      principles relating to "novel scientific evidence", the admissibility of BF in
      the various Australian jurisdictions is evaluated. The utility of BF in criminal
      investigations and counter-terrorism initiatives is also canvassed. The authors
      conclude that, at the present time, it is unlikely that expert testimony on BF
      will be admitted in Australian criminal trials. However, the technique
      potentially offers other benefits to the criminal justice system, thereby
      warranting its consideration as a "criminal and investigative tool of the
      future".

PMID- 16304762
TI  - The Schiavo and Korp cases: conceptualising end-of-life decision-making.
AB  - An incompetent, terminally ill patient can be viewed in two ways--as a person who
      is dying, when futile, life-prolonging treatment can be lawfully withdrawn; or a
      person with a disability, for whom a guardian must be appointed to decide about
      treatment. Terri Schiavo's husband took the first view and her parents the
      second. Maria Korp was regarded as dying when treatment was withdrawn. The
      difference in conceptualising a patient's situation is critical. Where a patient
      is dying, treatment can be lawfully withdrawn whatever the view of the relatives;
      they cannot require treatment to be continued. Where a patient has a disability
      and a surrogate decision-maker is appointed, the focus is on what the patient
      would have wanted in such circumstances, so that the surrogate can act in
      accordance with the patient's wishes. That deflects attention from the
      fundamental legal principle that whatever a patient or the relatives want, they
      are not legally entitled to demand treatment that doctors consider futile in the
      circumstances.

PMID- 16304763
TI  - Known semen donors: to be or not to be a parent.
AB  - The law has failed to keep pace with the reality that lesbian couples are
      conceiving children and raising families. At both Commonwealth and State levels,
      a complex web of legislation engulfs and winds its way through this area of the
      law. This article seeks to expose some of the bizarre and anomalous consequences
      that have emerged through the interaction of these provisions and the resulting
      judicial interpretations. It is argued that this incongruous, unsatisfactory
      situation cannot be allowed to continue. Uniform State and Commonwealth
      legislation must be enacted and existing Commonwealth legislation modified to
      avoid ongoing inconsistencies. Finally, legislative amendments are recommended
      which, it is argued, will go some way towards rectifying the situation.

PMID- 16304764
TI  - Navigating tissue banking regulation: conceptual frameworks for researchers,
      administrators, regulators and policy-makers.
AB  - In the "post-genomic" age of biomedical research, researchers often wish to
      utilise collections of human tissue. This type of research raises many ethical
      and legal issues and anyone wishing to use such collections is faced with an
      enormously complex set of regulatory requirements, many of which are still
      ambiguous, reflecting ongoing ethical and legal debate. Whilst there is no way of
      entirely avoiding such regulatory complexity and ambiguity, conceptual frameworks
      can assist those who wish to use, administer, authorise and generate policy on
      tissue banking research. Two conceptual frameworks are described here: a taxonomy
      of tissue banking practices, aimed at assisting those who need to ensure that
      tissue banks meet ethical and legal requirements; and a "syncretic" approach to
      policy-making, for those who wish to generate new policy, or streamline existing
      policy relating to tissue banking research.

PMID- 16304765
TI  - Advance directives and the persistent vegetative state in Victoria: a human
      rights perspective.
AB  - With advances in medical technology, it is now possible to sustain the life of a
      person in a persistent vegetative state (PVS) until a decision is made to
      withhold or withdraw life-sustaining treatment. Who makes that decision? Under
      the Medical Treatment Act 1988 (Vic) there is no legally enforceable right for a
      person to choose, in advance, what intervention that person will and will not
      accept if he or she ends up in a PVS. The best that can be achieved is that a
      person can appoint an agent who is empowered to refuse medical treatment on the
      person's behalf in the event of incompetence. It is suggested that this mechanism
      ignores two fundamental human rights: self-determination and the inherent right
      to dignity. This article proposes the development of an advance directive
      mechanism that provides for a person to refuse, in advance, specified
      intervention, thereby respecting fundamental human rights and alleviating the
      existing need for an agent to second-guess a person's desires and best interests.

PMID- 16304766
TI  - [The structural reorganization of chromatin as a process of its self-organization
      in eukaryotic cells and DNA repair problem].
AB  - Below were demonstrated the differences in the cell reaction of the chromosome
      loci transference induced by adaptive doses X-radiation in the cells nucleus in
      norm cells and in cells with repair process defect of the oncological patients
      and patients with hereditary disease. It was supposed that the transference of
      the homologous chromosome loci is necessary for the realization of the correct
      DNA's double strand repair. The chromosome loci transference in normal cells
      could be induced by different factors such as X-radiation, RNA-polymerize II
      repression by alpha-amanitin and possible by other factors. In cells with BSCA1
      and BRCA2 genes mutations the chromosome loci transference could not be induced
      by the X-radiation, but it could be induced by the RNA-polymerize II repression
      by alpha-amanitin. The defect of the chromosome loci transference condition on
      genetics or the another determinatives and this defect could be the one of the
      important reasons of the genome instability. There was suggested the new
      conception of the mechanisms of the cell differentiation and cell chronological
      senescence. The vector of the cell differentiation mechanisms is the progressive
      chromatin condensation determined by the physical mechanisms, i.e.,
      transformation from less probable (the stem cells) to more probable cell system
      state (the differentiated cells) and as a result of it changing of the genes
      transcription. The continued chromatin condensation (most pronounced in the old
      cells) decreases the probability of the realization of the DNA repair as the
      reason of the chromosome loci transference limitation. In this work are presented
      experimental and theoretical information that proves our conception.

PMID- 16304767
TI  - [Transposition of chromosome loci in bystander cells upon exposure to an adaptive
      dose of ionizing radiation].
AB  - During the process of the realization of the bystander effect the trans of the
      Signal from irradiated cells to the intact cell (bystander cells) happens. So
      both type of cells (irradiated and intact cells) have the same damages and
      reactions. There are new data about bystander effect as the transduction
      mechanism of the adaptive response and we have investigated this phenomenon.
      There are an incubation of the intact (bystander cells) and the exposed (X
      radiation of 10 cGy) human lymphocytes and we analyze the location of the
      centromeric loci of the first chromosome. We observed hat for the first time that
      after X-ray exposition of the adaptive doses the transposition of the chromosome
      loci from the peripheral to the central parts of the nucleus in intact (bystander
      cell) G0-lymphocytes which were incubated in the growth environment cells with
      irradiated cells removal. We support that the starting states of the adaptive
      response is the loci extrication of the matrix, the transposition and the
      approach homologous chromosomes. This process is necessary for the DNA double
      strand breaks reparation (in the case of injured dose X-radiation) with the
      participation of the homologous recombination.

PMID- 16304768
TI  - DNA loop organization and DNA fragmentation during radiation-induced apoptosis in
      human lymphocytes.
AB  - Apoptotic DNA fragmentation induced by gamma-rays has been compared with the DNA
      loop sizes in G0-human lymphocytes using pulsed field gel electrophoresis (PFGE).
      Genomic DNA was cleaved into the DNA loops at the topoisomerase II mediated
      attachment points using short treatment of cells with etoposide. The apoptotic
      fragmentation, with a distinct cut-off around 50 kb for a maximum length of
      fragments, appeared 5 h after irradiation when the most part of radiation-induced
      DNA double strand breaks (DSBs) have been repaired. The data indicate that
      apoptotic fragmentation of DNA in the G0-human lymphocytes begins when repair of
      radiation-induced DSBs has been completed. Similar apoptotic DNA fragmentation
      was also observed following the treatment of cells with etoposide. All genomic
      DNA was fragmented into 50-kb fragments during the final stages of apoptosis.
      Most of the DNA in resting lymphocytes is organized into Mb-size loops but loops
      of sizes down to 50 kb were also observed. A sharp border between the size
      distributions of DNA loops and apoptotic fragments was found. The data suggest
      that 50 kb apoptotic fragmentation is not based on excision of the DNA loops. No
      apoptotic fragments with the sizes more than 5.7 Mb were seen during the whole
      course of apoptosis. This observation indicates that despite intensive apoptotic
      fragmentation into the 50-kb fragments the chromosomes maintain integrity during
      radiation-induced apoptosis in human lymphocytes. We propose a model for
      radiation-induced apoptotic fragmentation in human lymphocytes that involves four
      stages: induction of DNA breaks and relaxation of DNA loops; DNA repair followed
      by reorganization of the DNA loops into the 50-kb units of condensed chromatin;
      co-operative fragmentation of the reorganized DNA loops into the distinct 50-kb
      fragments and resealing of the chromosome ends at the sites of this
      fragmentation; cleavage of the 50-kb fragments at the internucleosomal spacers.

PMID- 16304769
TI  - [Biophysical modeling of radiation induced genetic damage to cells].
AB  - The paper deals with the new approach for high accurate prediction of ionising
      radiation induced lesions of the cellular genetic structures. The previous
      techniques mainly were based on the assumption of the random radiation-induced
      breakage of the cellular DNA. They did not consider higher-order DNA organisation
      in the chromatin and in the interphase chromosomes. The paper discusses the new
      methods of the biophysical modelling of DNA breakage following high LET
      irradiation which takes into account the information on 3-dimensional structural
      organisation of DNA in interphase chromosomes. On this basis the influence of DNA
      organisation in the chromosomes on both dsb clusters induction and on repair were
      quantitatively studied, that was impossible by the means of previous
      computational techniques.

PMID- 16304770
TI  - [Molecular manifestations of radiation-induced genome instability: the
      possibility of chemical modification].
AB  - The molecular manifestations of radiation-induced genome instability-changes of
      the DNA structure, the excision DNA repair and the contents of the reactive
      oxygen forms in bone marrow cells of the repair proficient mice (CBA) and of the
      repair-defective (101/H) lines in the dynamics up to 185 day after ionizing
      radiation exposure in the dose of 1.5 Gy were studied. Is was established, that
      after irradiation in bone marrow cells the descendants with the decreased
      activity of excision DNA repair and prone to increased changes of DNA structure
      DHK is arised. The injection of the phenozane in concentrations causing its
      receptor interaction with cells, did not defend DNA of the bone marrow cells from
      the radiation injury after the exposure in a sublethal dose, however it exerted
      influence on long-term changes. Due to the phenosane of the bone marrow cells of
      the irradiated mice of CBA line exhibited the larger activity in a DNA repair
      from damages and maintenance of vitality. The bone marrow cells of male mice of
      repair defective 101/H line, which phenozan was entered before the irradiation,
      remained unfit to the remuval of DNA damages by the repair, that probably
      resulted the activations of the program of the maintenance of genome constancy by
      the apoptosis in the cells--carriers of the structural defects and the cause of
      animal lethality.

PMID- 16304772
TI  - [Level of nitric oxide and tumor necrosis factor-alpha production by human blood
      neutrophils under UV-irradiation].
AB  - The effect of the UV-irradiation (75.5-2265 J/m2) on the nitrogen oxide (NO) and
      the tumor necrosis factor-alpha (TNF-alpha) production by neutrophils of human
      blood was studied by Griess method based on the accumulation of NO2(-) -ions in
      the incubation matter and on the enzyme-linked immunosorbent assay (ELISA). UV
      irradiation in the dose of 75.5 J/m2 reveals the correctional effect relatively
      to the native level of NO, providing the maintenance of the physiological
      homeostasis. The irradiation of the neutrophils by the doses of 755 and 2265 J/m2
      increases the concentration of NO metabolites, that might lead to different
      pathologies. The process of NO-synthesis stopped during the incubation of these
      cells in the presence of the transcriptional inhibitor of the protein sunthesis -
      cycloheximid. This suggests that the NO generation by photomodified neutrophils
      is due to the activation of iNOS synthesis de novo by UV-irradiation. UV
      irradiation also has a modulating effect on the level of TNF-alpha production by
      phagocytes. The resulting effect depends on the native cytokine concentration.
      The positive correlation between NO and TNF-alpha concentrations in native and
      irradiated cells in the dose of 755 J/m2 was estimated, that shows close
      interrelationship between these parameters.

PMID- 16304771
TI  - [Radiolysis of liposomes, of solutions of ferrous sulphate and of albumin mixed
      by gamma-neutron radiation at different dose rates].
AB  - Solutions of the ferrous sulfate, of the albumin and of the suspension of
      liposomes were irradiated by mixed gamma-neutron radiation (fission spectrum
      neutrons, contribution of gamma-component to the absorbed dose up to 20%) at the
      pulse reactor BARS-6 with single-pulse (duration 100 micros) or continuous
      radiation (duration 60 min). It was shown, that after the pulse irradiation the
      concentration of the malonic dialdehyde in liposomes was in 3-4 times higher than
      after the continuous radiation at equal absorbed doses (p < 0.05). On the
      contrary, the irradiation of the liposomes suspension as well as of the solutions
      of the ferrous sulfate and of the albumin in a mode of single-pulse or of
      continuous mode did not reveal the statistically significant differences in the
      production of Fe3+ ions and of peroxides of the albumin for two mode of the
      radiation action.

PMID- 16304773
TI  - [Frequency of mutant lymphocytes in T-cell receptor locus as a possible predictor
      of thyroid cancer development in irradiated and unirradiated persons].
AB  - Was compared frequency of lymphocytes mutant at loci of T-cell receptor (TCR)
      from samples of peripheral blood taken from 186 healthy donors and 46 untreated
      thyroid cancer patients, including the persons exposed to ionizing radiation as a
      result of inhabitation in radioactive polluted region of Russian Federation. Was
      shown that the cell mutation rate within thyroid cancer group was significantly
      higher than the same parameter for the healthy person with similar age
      distribution (p < 0.01). It could be a result of such factors as genotoxic
      influence, different sensitivity or possible genome instability (including
      radiation-induced). It was found that 37% of patients have the increased
      frequency of somatic mutation cells, i.e. it exceeded 95% confidence interval for
      the screening group. The presented results cause to anticipate that TCR-test
      could be used as one of criteria for formation groups of high cancer risk
      development.

PMID- 16304774
TI  - [Level of microelements-metals in animal blood as an informative indicator of
      response to low-intensity short duration electromagnetic irradiation].
AB  - The comparison (juxtaposition) of the rats and the rabbits organism reactions on
      the electromagnetic irradiation (1.5 GHz, 300 microW/cm2, non-stop mode, 30 min)
      by the index of the physiological status indicators and of the blood
      microelements (ME)--metals concentration is presented. This physiological status
      indicators display that the mentioned irradiation is an underthreshold effect for
      central nerve system, which doesn't cause the essential changes on the organism
      level. In the same time, the reliable blood microelements-metals concentration
      shifts are established. And this let us suppose the ME-indicator as the most
      informative value of an organism reaction on the electromagnetic irradiations
      corresponding to the underthreshold effects for the central nerve system.

PMID- 16304775
TI  - [Action of mixed gamma-neutron radiation with various dose rates on the number of
      cells in thymus and chromosomes of mice bone marrow and human lymphocytes].
AB  - The irradiation with mixed gamma-neutron radiation was carried out at the pulse
      nuclear reactor on fast neutrons BARS-6 in a regimen of one pulse (100 micros)
      and in a regimen of continuous irradiation during 60 minutes. Was shown, that the
      irradiation of mice with pulse radiation was 1.3-1.8 times more effective in the
      induction of the chromosome aberrations in bone marrow cells in comparison with
      the continuous regimen of irradiation. At the same time, other biological tests
      (yield of chromosome aberrations in human lymphocytes, decreasing the number of
      cells in thymus) demonstrated that pulsed and continuous regimens have almost
      equal biological effectiveness.

PMID- 16304776
TI  - [Plasticity of neuroendocrine transducers under the combined influence of the
      radiation and light exposure].
AB  - The structural changes of neurons of the rat hypothalamic supraoptic (SON) and of
      paraventricular (PVN) nucleus after 48 h of bright light exposure, of 5 Gy whole
      body X-irradiation and of their combination subjected to the analysis by means of
      light-optic and of electron microscopy for the estimation of radimodificated
      effect of light exposure lasted 24 h a day and plasticity of neuroendocrine
      transducers interacted with the optic sensory system. The structural changes of
      neurons of the SON after combined action are less considerable and more prolonged
      in comparison with the PVN that loas defermined by their direct connection with
      the optic sensory system via the retinohypothalamic tract.

PMID- 16304777
TI  - ["Ischemia/reperfusion" for stem cells of two "critical" cell renewal systems of
      organism].
AB  - In this article is presented the result of the experiments on mice-hybrids F1(CBA
      x C57B1/6), which indicates the presence of the reaction of
      "ischemia/reperfusion" for stem cells of two "critical" cell renewal systems of
      organism (bone marrow and intestinal epithelium) during the irradiation under the
      conditions of hypoxic radioprotector application. The additional injection of the
      source of nitric oxide radicals-sodum nitroprusside (SNT) to the mice right after
      the irradiation under the conditions of hypoxic protection by serotonin, resulted
      the substantial increase of the survival rate of hematopoietic stem cells
      (registered by the methods of endogenous and exogenous colony forming in spleen)
      and stem cells of intestinal epithelium (registered by the method of intestinal
      "microcolonies"). The similar radioprotective effect was also registered during
      the test of survival rate of mice under tests of "bone marrow" and "intestinal"
      forms of radiation lethality that is evidence of the importance of the
      realization of phenomenon "ischemia/reperfusion" in the reaction of whole
      organism on the acute radiation injury. As SNP weakens the manifestation
      apoptosis and necrosis through competition with active forms of oxygen (AFO)
      during the period of "reperfusion" on basis of the found out phenomenon
      experimental model for studying mechanisms of stem cells damage in vivo induced
      by AFO and for the search of the modifiers weakening or strengthening such damage
      can be developed.

PMID- 16304778
TI  - [Modifying properties of 2,5-diphenyloxazole during low-dose X-ray exposure of
      mice].
AB  - The ability of 2,5-diphenyloxazole (DPO) to modify biological consequences of the
      X-rays irradiation of mice was studied with a dose of 16 cGy at the
      administration of the agent in a wide range of concentrations before or after
      irradiation was studied. It was shown that the administration of the agent in
      doses 9.9 x 10(-3)-9.8 mg/kg 35-60 min before irradiation causes a reliable
      decrease in the spleen mass within 1 month after the action; for the dose 1
      mg/kg, it causes the tendency to decrease of the content of lipid peroxidation
      (LPO) products; the dose 9.8 mg/kg causes a decrease in the cell-free DNA amount
      in blood plasma of mice. The administration of DPO before irradiation causes
      changes in the scale and direction of the correlation between the DNA and LPO
      products contents in blood plasma of irradiated mice compared with the control.
      The administration of DPO 15-60 min after irradiation do not cause any reliable
      changes in the investigated parameters. The aviability of the study of the
      radioprotective properties of the DPO derivatives as agents with a nontraditional
      character of action is supposed.

PMID- 16304779
TI  - [Assessment of hemapoietic system reaction of mice when exposed to pulsed
      magnetic field].
AB  - The focus of the study was on the reaction of by the haemopoietic system of mice
      subjected to impulse magnetic field. The source of the impulse magnetic field was
      the Shakhparonov's generator. The animals used in the experiments were mice of
      two strains--CBA, C57B1/6 and white non-inbred mice. These animals were exposed
      to impulse magnetic field during 1, 3 and 7 days. Animals were examined twice:
      immediately after the termination of exposure and 24 h later. The following
      effects were observed in the course of the experiments: an increase in the number
      of bone marrow cells right after the exposure termination; an increase in the
      number of proliferation pool cells with the increase in their mitotic activity; 1
      day after the exposure termination the number of bone marrow cells was restored
      to the initial values, or even it decreased; the above listed bone marrow changes
      led to the increase in the number of peripheral blood leucocytes in 1 day after
      the termination of exposure. The increase of leukocyte counts was not accompanied
      with changes in peripheral blood cell composition. It was suggested that exposure
      to impulse magnetic field increases the rates of cell cycle, the cell
      differentiation and the maturation.

PMID- 16304780
TI  - [Cytogenetic characteristics of seed progeny of common oak trees (Quercus robur
      L.) exposed to the irradiation after the accident at the Chernobyl Nuclear Power
      Station and growing at the territories with different levels of anthropogenic
      contamination].
AB  - The examination of cytogenetic characteristics (the mitotic activity, the time of
      passing of the mitotic stages by cells, the level and the spectrum of mitosis
      disturbances, the nucleoli characteristics) of seed progeny of common oak trees,
      exposed to the radiation exposure after the accident at the Chernobyl Nuclear
      Power Station and growing at the territories with different levels of
      anthropogenic contamination was held. In spite of the normalization of the
      radioactive level at the examined territories the changes of the cytogenetic
      characteristics of common oak seed progeny in comparison with the control were
      noticed. Obtained results are explained from the position of the radiation
      induced genomic instable and of the wave kinetic of the mutation process. The
      questions of the advisability and of the validity of using of the seed progeny of
      the common oak trees, exposed to the radiation exposure, in forest restoration
      measures are discussed.

PMID- 16304781
TI  - [Radioecological problems in coastal landscapes of the Sea of Azov].
AB  - The features of the spatial distribution, of the migration, and of the
      accumulation of natural (232Th) and manmade (137Cs) radioactive nuclides in the
      coastal landscapes of the Sea of Azov are studied. It was shown, that the
      specific activity of 232Th in the accumulation of the so-called "black sands" was
      shown as high as 6000 Bq/kg, that increases the natural geochemical background in
      200 times. The impact of aerial transfer of the "black sands" on 232Th migration
      and accumulation in the soil-plant system was clarified. The 232Th distribution
      down the soil profile suggests that the "black sands" are likely the product of
      the erosion of the coastal parent materials enriched by natural radionuclides. In
      general, the specific activity of 137Cs in the beach sand is not high and it is
      close to the background (global fallout) value. It was determined that 137Cs
      content in the coastal ecosystems is connected only by aerial pathway as a part
      of global and Chernobyl-born fallout.

PMID- 16304782
TI  - The clinicians CPOE forgot. Vendors, take note: a lot of IT use is by midlevel
      practitioners.

PMID- 16304783
TI  - A winning combo. Small clinics see big gains in teaming up practice management
      and medical record systems.

PMID- 16304784
TI  - Code talkers. Some are eager, others much less so, for the ICD-10 standards to
      take effect.

PMID- 16304785
TI  - Big game hunting. In a CIO search, look inside and outside the company for
      business and people skills.

PMID- 16304786
TI  - Direct route to better care. For healthcare to arrive at next-generation disease
      management, IT must be the driver.

PMID- 16304787
TI  - Follow your passion. John Glaser's special strength is building collaborations
      and bringing them to life.

PMID- 16304788
TI  - EMRs and EHRs. Concepts as different as apples and oranges at least deserve
      separate names.

PMID- 16304789
TI  - Better outcomes of hard labor. Niche vendors offer automated tools to improve
      safety in obstetrics.

PMID- 16304790
TI  - Keeping healthy contracts. Technology can maintain sound agreements and
      compliance.

PMID- 16304791
TI  - Managing web site content. Patients can follow their path of care online with a
      well-conceived web site and portal.

PMID- 16304792
TI  - Deception detection. Intelligent software keeps medicare fraud in check.

PMID- 16304793
TI  - Care versus caring: hospitals lose their way.

PMID- 16304794
TI  - Use of magnetic resonance imaging in differentiating compartmental location of
      spinal tumors.
AB  - Magnetic resonance imaging (MRI) is the best imaging modality for evaluating most
      spinal tumors. In this review, we describe the MRI appearance of extradural,
      intradural-extramedullary, and intradural-intramedullary tumors as well as the
      image interpretation techniques that permit identification of the compartment in
      which a lesion is located. In addition, we review the literature and our
      experience in using an anatomic classification system to narrow the differential
      diagnosis for patients with spine tumors. This method permits successful
      identification of a narrow differential diagnosis, which can be used to guide
      additional evaluation and treatment.

PMID- 16304796
TI  - Musculoskeletal workload versus musculoskeletal clinical confidence among primary
      care physicians in rural practice.
AB  - We studied the prevalence of musculoskeletal conditions in a rural Oregon primary
      care practice and the self-assessed musculoskeletal knowledge and skills of
      primary physicians practicing in the area. We recorded how many musculoskeletal
      complaints were evaluated and treated in a primary care physician's office
      between April 1 and April 30, 2002. In addition, to all primary care physicians
      in the surrounding county, we distributed a self-administered questionnaire
      assessing physician confidence regarding common musculoskeletal conditions and
      procedures. Prevalence of musculoskeletal conditions for the month was 17.5%
      (48/274 office visits). Questionnaire results indicated that local physicians
      felt relatively uncomfortable with common musculoskeletal conditions (mean
      confidence scores on a 10-point Likert scale: 4.2, musculoskeletal conditions;
      9.0, nonmusculoskeletal medical conditions). These findings suggest a disparity
      between rural primary care physicians' self-assessed musculoskeletal knowledge
      and skill and the levels they require for their practice.

PMID- 16304795
TI  - Orthopedic management of hemophilia.
AB  - Hemophilia is an X-linked inherited bleeding disorder characterized by a
      deficiency of clotting factor VIII or IX in the intrinsic pathway of the
      coagulation cascade. This disease can have a profound, debilitating effect on the
      musculoskeletal system through recurrent hemarthroses and intermuscular
      hematomas. Although medical management with replacement factor is often
      effective, patients with severe hemophilia may develop chronic synovitis and
      arthropathy best treated with more invasive means. Radioactive synovectomy
      performed at select hemophilia centers and arthroscopic or open synovectomy are
      helpful for chronic, active synovitis. Arthroplasty helps improve function and
      pain relief for most patients, but complication rates, particularly for
      infection, are higher than those for arthroplasty performed on patients without
      hemophilia.

PMID- 16304797
TI  - Tibiofibular synostosis procedure in the management of complex tibia fractures.
AB  - Complex tibia nonunions and defects caused by tumor, trauma, and congenital
      abnormality are difficult to treat. The tibiofibular synostosis procedure is a
      treatment option. Fifteen patients with complex diaphyseal tibia fractures (4
      segmental, 11 comminuted; 10 open, 5 closed) were managed with this procedure.
      Mean time between injury and procedure was 20.3 weeks. Mean healing time was 16
      weeks (acceptable); 14 of 15 cases showed healing by final follow-up (36 months).
      At final follow-up, each patient's knee range of motion (ROM) and ankle ROM were
      acceptable. Knee ROM varied from full extension to 150 degrees of flexion for 13
      patients and from full extension to 120 degrees of flexion for 2 patients. Ankle
      dorsiflexion ranged from 0 degrees to 40 degrees for 10 patients, from 0 degrees
      to 30 degrees for 3 patients, and from 0 degrees to 20 degrees for 2 patients.
      There were no radiographic arthritic changes in any case. The tibiofibular
      synostosis procedure is effective in treating complex nonunions and defects.

PMID- 16304798
TI  - Acute compartment syndrome of the upper arm: a report of 2 cases.
AB  - Compartment syndromes of the upper arm are rare clinical entities but can be a
      serious problem, especially in unconscious patients or those presenting with
      altered mental status. A high index of suspicion is needed to make an accurate
      diagnosis. Measuring compartment pressures is helpful, but the role of pressure
      measurement in the diagnosis and treatment may be secondary to the clinical
      examination. In patients presenting without histories of trauma, who have
      sustained long periods of immobilization, a suspicion of a crush syndrome should
      also be included during the workup of a compartment syndrome. Fasciotomy and
      debridement of necrotic and nonviable tissue are the treatments of choice for a
      patient with a compartment syndrome, but initiating medical management and
      providing medical stability for systemic complications resulting from a crush
      syndrome may be necessary prior to surgical intervention to prevent organ failure
      and death. Overall, prognosis is improved by early diagnosis and treatment.

PMID- 16304799
TI  - Repeat patellar tendon rupture in a child.
AB  - In summary, we present the first published case of a patellar tendon midsubstance
      rupture in an otherwise healthy 9-year-old with repeat rupture at age 10.

PMID- 16304800
TI  - Traumatic simultaneous rupture of both flexor tendons in a finger of an athlete.
AB  - We report a case of traumatic simultaneous disruption of both finger flexor
      tendons in a professional athlete. The novelties in this report are (1) the
      location of the rupture (FDS at midsubstance and FDP at insertion) and (2) the
      proposition that a normal but diminutive FDS tendon is a contributing factor in
      the rupture. We recommend that simultaneous rupture of the normal flexor tendons
      be treated in a similar manner as tendon lacerations. Primary repair, if
      possible, is the treatment of choice in these acute injuries. Tendon grafting
      should be reserved for subacute or chronic cases in which restoration of active
      finger flexion is needed.

PMID- 16304801
TI  - Reminder: radiopacities from metal-containing substances.
AB  - A 17-month-old boy with a toed-out left lower extremity was presented for
      evaluation. Before coming to the doctor, the mother had applied a zinc oxide
      lotion to treat a simple diaper rash in the groin. The radiologist did not remove
      the boy's diaper for the radiographic examination and so did not notice the
      lotion. The first radiograph showed what looked like multiple soft-tissue
      calcifications in the groin, but the radiopacities had been produced by the zinc
      oxide. This case serves as a reminder to be aware that metal-containing
      substances both on and in the body can produce radiopacities.

PMID- 16304802
TI  - [Current concepts of the antiplatelet and anticoagulant treatment in the
      prevention of stroke].
AB  - About 80% of strokes have ischemic origin. Therapeutical options of acute stroke
      are still limited and the occurrence of recurrent strokes is remarkably high.
      Consequently, the adequate stroke prevention has a high importance. The two main
      components of prevention are the inhibition of platelet aggregation and the
      anticoagulant therapy. Results of multicenter drug trials showed that
      antiaggregation therapy can reduce the risk of recurrent stroke by ca. 25%.
      Acetylsalicylate has been used for stroke prevention for decades. Nowadays, there
      is a broad spectrum of available platelet aggregation inhibitors. The efficacy of
      these new drugs is higher than that of acetylsalicylate. According to recent
      therapeutical guidelines, the antiaggregation therapy of patients with non
      cardiometabolic stroke should be optimized individually. The most frequent cause
      of cardiogenic stroke is atrial fibrillation. The importance of anticoagulation
      therapy has been proved by large multicenter studies. Absolute therapeutical
      indications are the elder age, additional risk factors, previous stroke.
      Therapeutical guidelines in other cardiological disorders associated with high
      risks for stroke need further drug trials. Fifty years after the introduction of
      warfarin, in the last years new direct thrombin inhibitors have been developed.
      These drugs have the same efficacy as warfarin but they are a more safety and
      have more simply therapeutical administration.

PMID- 16304803
TI  - [Types and systems of symmetry and their multiplicity in the adenovirus protein
      coat. I. Symmetry networks and general symmetry motives].
AB  - Each of the more than 1500 polypeptide molecules of 7 different types building up
      the adenovirus capsid--probably even those of their amino acids--are in
      symmetrical location. Every kind of polypeptide forms also a separately
      symmetrical network in the capsid distributed according to their functions in the
      inner and outer side and inside of the facets and edges, but always in compliance
      with the icosahedral symmetry. Therefore, each different polypeptide also means a
      general symmetry motif in the capsid in its own symmetry network. Hexons can be
      considered as general symmetry motifs in some special association that is because
      of their environmental position four kinds of hexon types can be found, which are
      on every facet, next to one another, like three identical groups of four hexons
      according to the three-fold rotational symmetry. Two polypeptides of a
      peripentonal hexon of each group of four hexons orient towards the penton and the
      third toward the other penton located further on the same edge. There are two
      versions of the arrangement of the group of four hexons: the hexons surround
      either a polypeptide IX or a polypeptide IIIa. The two versions of group of four
      hexons on 20 facets symmetrically recurring 60 times as general hexon symmetry
      motifs form the capsid in combination with the network of other polypeptides.
      Ideally, the surface of the hexon trimer shows three-fold rotational and three
      fold reflexional symmetries. In the arrangement of the hexons in the facets the
      translational, rotational, horizontal and vertical reflexional symmetry and the
      combination of these, as well as the glide reflexion and the anti-symmetry can be
      found. Each hexon has six nearest neighbours and every hexon takes part in the
      construction of three hexon rows. Every facet and every vertex made up of five
      facets has an anti-symmetrical pair located on the opposite side of the capsid.
      Every triangular facet participates in forming three vertices and every facet has
      three nearest neighbouring facets. In the facets, the polypeptide subunits of the
      polypeptide IX centered group of four hexons have identical counter-clockwise
      orientation but the orientation of the neighbouring facets is always opposite
      compared to each other. On the five-fold symmetry axis, any facet can be "turned
      on" to the adjacent facet or "rotated" to all the others and will take the
      symmetry and orientation of the facet it got turned on or rotated to. Thus, every
      facet together with the polypeptides attached to it shows a twenty-fold symmetry
      and multiplicity. Another type of symmetry and multiplicity in the capsid is that
      perpendicular to the 6 five-fold rotation axes a geodetic (equatorial) ribbon
      like motif (superfieces) altogether six made up of 10-10 triangular facets and
      bent ten-times with an angle of 36 degrees. A triangular facet participates in
      forming three ribbon-like motifs, which intersect with each other on the given
      facet but the same three motifs intersect only on the anti-symmetrically located
      facet.

PMID- 16304804
TI  - [Sarcoidosis (after cosmetic intervention)].
AB  - The authors' report a case of a 26-year-old female. In 1996, and 1997 she
      underwent cosmetic lip augmentations (polymethyl methacrylate and silicone).
      After a six-year symptom free period sudden swelling of the lips developed and
      red-brown papules and subcutaneous nodules appeared in the scars of various body
      parts ( permanent make-up, tattoos, umbilical piercing). The clinical features,
      radiological signs and histology proved the diagnosis of systemic sarcoidosis.
      Systemic corticosteroid treatment was introduced. After 4 months of treatment the
      pulmonary and clinical symptoms showed regression. To be able to suspend the
      systemic treatment the silicone implant was removed.

PMID- 16304805
TI  - [Prolonged hiccups causing worsened quality of life--successful medical therapy].
AB  - Hiccups are intermittent, involuntary spasmodic contractions of the diaphragm and
      the intercostal muscles leading to the cessation of inspiration due to an abrupt
      closure of the glottis. Hiccups are usually innocuous phenomena, which could
      easily be terminated by simple manoeuvres but sometimes they become permanent and
      intractable causing significant decline in the patient's quality of life. Besides
      a number of provoking exogenous factors hiccups are caused by organic or
      psychical disorders. This why in cases of permanent hiccups detailed
      investigations are important. Beyond physical manoeuvres, pharmacotherapy,
      surgical intervention and some other therapeutic measures may be effective forms
      of treatment. In the present report the authors give a review of two patients,
      whose permanent hiccups were successfully treated with combined medical therapy.
      They review the causes and therapy of permanent hiccups and call the attention to
      the therapeutic value of baclofen, a gamma-aminobutyric acid analog compound.

PMID- 16304806
TI  - [Type I antithrombin deficiency as a cause of arterial and venous thrombosis in a
      family with severe thrombophilia].
AB  - INTRODUCTION: In rare cases of thromboembolic diseases developing in young age,
      venous and arterial thromboembolism can occur simultaneously. AIMS: To detect the
      venous and the arterial risk factors in a severe thrombophilic family. A 47-years
      old female with severe atherosclerosis and recurrent deep vein thrombosis, and 6
      members of her family were analysed. METHODS: The following haemostatic and
      molecular genetic investigations were performed: besides the rutin haemostatic
      parameters, risk factors for venous thrombembolic disease, risk factors for
      venous and arterial thrombosis (plasma homocysteine level, MTHFR C677T
      polymorphism) were determined. This panel was completed with the measurement of
      lipoprotein (a), von Willebrand factor, plasminogen activator inhibitor-1
      antigen, serum total cholesterin, HDL cholesterin, C reactive protein and PIA2
      variant. The propositus was proven to have type I antithrombin deficiency,
      elevated homocysteine level, homozygous MTHFR C677T polymorphism, elevated Lp(a),
      vWF:Ag, and PAI-1:Ag levels. RESULTS: All family members had a combination of
      cardiovascular risk factors (in 4 cases elevated homocysteine level, in 3 cases
      elevated Lp(a), in 2 cases elevated vWF:Ag, in 4 cases increased PAI-1 level).
      These risk factors were combined in three cases with type I antithrombin
      deficiency. Despite of the presence of atherosclerotic risk factors in the
      family, arterial thrombotic disease could be detected only in two patients with
      antithrombin deficiency. CONCLUSIONS: The results of the investigated family
      indicate that in case of combination of venous and arterial thromboembolic risk
      factors, antithrombin deficiency may contribute to the manifestation of arterial
      thromboembolic diseases.

PMID- 16304807
TI  - [Non-channel drugs to prevent atrial fibrillation].
AB  - Atrial fibrillation is the most prevalent sustained cardiac arrhythmia. To
      terminate or prevent atrial fibrillation, conventional "channel-blocking
      antiarrhythmics" are generally administered, which directly inhibit current flows
      through transmembrane sodium, calcium and/or potassium channels that give rise to
      the atrial action potential. However, prospective, randomized clinical trials
      have demonstrated that cardiomyocyte ion channel blocking antiarrhythmic drugs
      have limited long-term-efficacy for preventing recurrences of atrial
      fibrillation, their safety is far from ideal (because of the high incidence of
      proarrhythmic and extracardiac side-effects), and do not reduce mortality.
      Researchers during the last 10 years have revealed that the pathogenetic basis of
      the recurrence, persistence or permanence of atrial fibrillation is electrical
      and structural remodelling established by profound alterations in the
      electrophysiological, contractile and (ultra)structural properties of the
      myocardium (atrial remodelling). Accordingly, recent interest has shifted from
      ion channel blockers to the development of drugs that target underlying
      arrhythmogenic substrates by interference with receptors and specific signal
      transduction pathways involved in electrical and structural remodelling (non
      channel drugs). They include antifibrotic angiotensin-converting enzyme
      inhibitors, angiotensin II AT1 receptor and aldosterone antagonists, beta
      adrenergic blockers, anti-inflammatory statins and glucocorticoids, and a series
      of new atrioselective antifibrillatory agents that are currently undergoing
      clinical trials.

PMID- 16304808
TI  - [Intravenous immunoglobulin treatment of recurrent spontaneous abortion with
      immunopathological background].
AB  - INTRODUCTION: Recurrent spontaneous abortion (RSA) is diagnosed if three or more
      spontaneous abortions follow each other typically in the first trimester. The
      root cause of miscarriages often can not be found. A significant proportion of
      this unexplained RSA cases may be caused by immunopathological failure. AIM: A
      multicentric clinical study started in 2000 to introduce an immunological
      screening protocol for patients suffering in idiopathic habitual abortion, and to
      use immunotherapy for their treatment if immunological background was defined.
      METHOD: The general checkup of the patients was managed based upon a detailed
      protocol, with which non-immunopathological reasons for RSA were excluded. The
      unexplained RSA cases underwent an immunological checkup including cellular and
      humoral immunological, immunogenetic and autoimmune examinations. Based upon
      these parameters, the immunopathological background of RSA was certified or
      excluded. In the confirmed immunopathological cases intravenous immunoglobulin
      (IVIG) therapy was applied during their next pregnancy, with continuous
      monitoring of the immunological parameters. RESULTS: 120 patients with RSA were
      examined, and 32 of them got IVIG therapy during their next pregnancy. In 72% of
      cases (23/32) IVIG treatment for RSA with immunopathological alloimmune
      background was successful, with the outcome of healthy newborn. Of the 9
      unsuccessful cases, in 6 patients subsequently additional non-immunopathological
      reasons were diagnosed for their RSA. IVIG treatment of patients with clear
      alloimmune background was successful in 88.5% (23/26). CONCLUSION: Results show
      that immunopathological checkup and immunotherapy is a useful treatment in the
      modern medicine for the patients with unexplained RSA. However the success of
      this method depends on the adherence of the checkup protocol, because
      unsuccessful therapy of non-clear cases can reduce the efficiency.

PMID- 16304809
TI  - [The management of bronchial asthma during pregnancy--Hungarian experiences].
AB  - INTRODUCTION: The prevalence of bronchial asthma is 4-8% among pregnant women.
      The complications, which threaten the asthmatic pregnancies according to the
      literature, are the following: spontaneous abortion, diabetes mellitus, caesarean
      delivery, pre-eclampsia, low gestational weight, neonatal icterus. OBJECTIVE: The
      aim of the study was a retrospective analysis of the data of asthmatic pregnant
      patients managed between 2000 and 2004, with a special consideration on the
      treatment and gynecologic complications. METHODS: The data of 53 persistent
      asthmatic patients--who had already undergone delivery--were collected. All of
      them were treated according to the guidelines issued in 2000 by the American
      College of Allergy, Asthma and Immunology and the American College of
      Obstetricians and Gynecologists: the inhalative corticosteroid budesonide, the
      long-acting beta-agonist formoterol or salmeterol and the short-acting beta
      agonist terbutaline were used. RESULTS: The mean peak expiratory flow of the
      asthmatic pregnant patients was 71 +/- 16% of predicted, and the mean partial
      arterial oxygen tension 96 +/- 9 mmHg (means +/- SE). 10 of the 53 patients had
      cesarean delivery, 3 developed pre-eclampsia, 1 diabetes mellitus. The mean
      gestational age was 38.84 +/- 2.17 weeks and the weight of newborns 3132 +/- 604
      g. The hospitalization was prolonged due to the infants' hyperbilirubinaemia in 3
      cases. No congenital malformations or spontaneous abortions were detected.
      CONCLUSION: Based on the results of this retrospective study it can be concluded,
      that bronchial asthma slightly decreases the weight of newborns. The appropriate
      treatment of asthma during pregnancy resulted that the prevalence of gynecologic
      complications did not exceed the prevalence observed in the normal population-
      without increasing the risk of congenital malformations.

PMID- 16304810
TI  - [Endemic hepatitis E infections in South-East Hungary].
AB  - INTRODUCTION: Hepatitis E virus (HEV) one of the most important infectious agent
      in acute hepatitis in tropical and subtropical areas. Recently, it has been
      demonstrated that HEV infection also occur in developed countries without travel
      history. In these regions, transmission thought to be zoonotic. In this work
      hepatitis E cases are detected in South East Hungary. AIMS: Aims of the authors
      were the detection of HEV infection in acute hepatitis patients by enzyme
      immunoassay (ELISA), and the introduction of clinical and epidemiological
      features. METHODS: Between January 2001 and October 2004, acute sera samples were
      tested by serological methods (enzyme-immunoassay for HEV IgM and IgG antibodies)
      from patients with acute hepatitis observed in Department of Infectology Hospital
      of Szeged. Samples from non-A-B-C infections hepatitis were tested. CONCLUSIONS:
      In the mentioned period the detected HEV infections (27) showed a similar
      incidence as known in other hepatitis in our region. Based upon our results,
      hepatitis E virus is one of the etiological agent in acute endemic hepatitis in
      South East Hungary, with special clinical features, which are not entirely
      similar, found in available literature. The gained data, with their conclusions
      may have wilder professional interest.

PMID- 16304812
TI  - [The consideration on medical accidents associated with surgery].

PMID- 16304811
TI  - [Total upper lip necrosis and loxoscelism caused by violin spider bite].
AB  - Arthropods and in particular spiders are a common embodiment of our fears,
      despite the fact that only a few species are dangerous to man. The authors
      present a case involving severe local and general reactions to a loxosceles
      (brown recluse spider) bite. They give an overview of the occurrence of
      loxosceles spiders, the signs and symptoms of envenomation and the therapeutic
      possibilities. The severe symptoms presenting following loxosceles envenomation
      is termed loxoscelism. Loxoscelism is characterised by local soft tissue necrosis
      of varying degree at the site of the sting, and rarely, life-threatening general
      reactions, such as haemolysis with ensuing anaemia, and renal failure.
      Therapeutic interventions following loxosceles bites range from dapsone treatment
      to hyperbaric oxygen therapy, but the most promising therapy is the use of the
      antiserum, commercially available in certain South-American countries where
      loxosceles bites are common. Treatment of soft tissue necrosis consists of
      necrectomy and surgical reconstruction following the resolution of the
      inflammatory symptoms.

PMID- 16304814
TI  - [The frontiers of diagnostic radiology--PET/CT, 3DCT--].
AB  - Recently, positron-emission tomography (PET) systems have been introduced in many
      institutions around Japan and their clinical importance should increase in the
      management of many malignant diseases particularly systems using 2-[fluorine-18]
      fluoro-2-deoxy-D-glucose (FDG). Since March 2004, we have been using the first
      PET/computed tomography (CT) scanner in Japan with 4-slice multidetector CT
      (MDCT) and now have introduced a second PET/CT scanner with 8-slice MDCT because
      of its excellent diagnostic capability and higher throughput capacity than that
      of the ordinal PET scanner. MDCT was a landmark in the history of CT in 1998.
      Subsequently, 8-, 16-, 32-, and 40-slice MDCT was developed in rapid succession.
      Finally, 64-slice MDCT became commercially available in 2005. In the future, 256
      slice MDCT and flat-panel CT will appear in the clinical setting. Using these
      MDCT systems, we can now obtain multidimensional CT images very easily. These
      multidimensional images are less-invasive methods that are gradually phasing out
      the use of invasive angiography including digital subtraction angiography. In
      this article we describe the current features of PET/CT and multidimensional CT
      using MDCT.

PMID- 16304815
TI  - [Capsule endoscopy].
AB  - Wireless capsule endoscopy is a new diagnostic tool in which a disposable video
      capsule is swallowed by the patient. This examination enables visualization of
      the small intestine that is not within the reach of conventional upper and lower
      endoscopy. The best indications include an obscure source of gastrointestinal
      bleeding, Crohn's disease, and small intestinal tumors. The disadvantage that
      biopsy cannot be performed is compensated for by employing double-balloon
      endoscopy. In particular, this examination can identify the origin of bleeding
      and diagnose the underlying disease, leading to prompt surgical treatment with
      better results. In future, capsule endoscopy will become a necessary examination
      for diagnosing digestive tract disease.

PMID- 16304816
TI  - [Robot-assisted surgery].
AB  - Computer-enhanced surgical systems are becoming common worldwide. Currently, 331
      da Vinci surgical systems have been installed. Robotic surgery was successfully
      performed on more than 20,000 patients in 2004. Intuitive Surgical has received
      FDA clearance for laparoscopic and thoracoscopic procedures, including
      hysterectomy or prostatectomy, as well as cardiac revascularization. The Japanese
      "Future Project" team has developed a prototype of a smaller surgical robotic
      system and successfully performed telesurgery on animals between Tokyo and
      Fujinomiya on August 8, 2002, and between Fukuoka and Seoul on March 2, 2005.
      Robotic surgery will lead to dramatic progress in medicine with the development
      of surgical navigation systems, simulation systems, and telementoring systems.

PMID- 16304817
TI  - [Implantable artificial heart].
AB  - Heart transplants have been decreasing globally due to the lack of available
      donor hearts. As a result, the increased use of artificial hearts is anticipated
      as an alternative therapy. Although biocompatibility issues, such as thrombus
      formation/thromboembolism and infection, are still the main cause of mortality
      associated with artificial hearts, more than 20 different types are now
      clinically available after a half-century of development and experimental trials.
      These devices range from extracorporeal pneumatic to implantable battery-powered
      artificial hearts. The early development of artificial hearts logically focused
      on volumetric pump designs incorporating functions similar to the natural heart.
      Today, development has shifted toward designs that are significantly different
      from the natural heart. These pumps utilize axial or centrifugal flow allowing
      for a much simpler design, which is smaller in size and has very few moving
      parts. With rapid advances in technology, this new generation of artificial heart
      pumps is beginning to emerge as an alternative to heart transplants.

PMID- 16304818
TI  - [Medical applications of nanotechnology: polymeric micelles for drug delivery].
AB  - Recently, medical applications of nanotechnology have received much attention.
      Among them, drug delivery systems (DDSs) are expected to be the leading
      technology in diagnostic and therapeutic medicine. An increasing number of DDSs
      have been approved for clinical use or are currently being studied in clinical
      trials. Polymeric micelles, self-assemblies of block copolymers, are one of the
      most refined and promising modalities of DDSs, since the critical parameters such
      as size, drug loading, and release can be controlled by engineering the
      constituent block copolymers. It has been demonstrated that polymeric micelles
      show unique disposition characteristics in the body suitable for drug targeting
      (e.g., prolonged blood circulation and significant tumor accumulation). Also,
      recent advances in polymer synthesis have allowed the development of polymeric
      micelles with integrated smart functions such as environmental sensitivity and
      targetability. Thus polymeric micelles might have great potential for
      nanotechnology-based DDSs for clinical use.

PMID- 16304819
TI  - [Genome analysis and cancer therapy].
AB  - Application of the human genome information would lead to the development of
      novel diagnostic methods and innovative therapies against cancer. In this
      article, two aspects of such application are reviewed; 1) genomic diagnosis for
      predicting efficacy and side effects associated with the administration of the
      anti-cancer drugs, 2) exploration of novel cancer associated gene products using
      genome-wide gene-expression profiling. Successful examination on genetic
      information of the patients/tumors would lead to the establishment of the
      "personalized" medicine which could be an ideal situation for the cancer patients
      treated with the chemotherapeutic drugs. Furthermore, the finding of tumor
      associated antigens lead to the development of not only new diagnostic methods
      but also novel therapeutic modalities including cancer vaccine. Some of the
      successful efforts are referred and discussed.

PMID- 16304820
TI  - [On the role of clinical information system in near future].
AB  - Information and communication technology has been growing up so rapidly. But, we
      should not forget that what we call "information" implies "digital in format".
      The digitalized information is essential for transmitting, sharing by many people
      in real time, processing, fusing, and so on. Creating three-dimensional CGs from
      a set of large volume image data or doing curved reformation can be performed in
      a blink of an eye. Now, it is also easy for an operator to get to know the
      stiffness of the organ through a manipulator by using the power-feedback
      technology. Organic integration of a variety of medical information provide a new
      virtual reality world which is valuable space such as a collaboration work place
      in a operation field. This is one of a model of the information assisted
      operation system. Therefore, the reader can easily understand that once he get
      the digitalized information, all that is left is not the technique but the
      "sensibility". This article is designed for readers to get to know above
      mentioned technical aspect and its applicable system. Finally, I believe that
      technologies regarding the medical information system could contribute to some
      activities in the surgery in near future.

PMID- 16304822
TI  - [Surgical scalpel and palm treatment].

PMID- 16304823
TI  - [What we can learn from a case of medical malpractice].

PMID- 16304824
TI  - [Breast conserving treatment].

PMID- 16304825
TI  - [Primary leiomyoma of the liver: a case report].
AB  - A 61-year-old woman was referred to our hospital due to a liver tumor discovered
      at a medical checkup. A hypervascular tumor located in liver segment I, measuring
      45 mm in diameter, was visualized on ultrasonography. The tumor showed strong
      uniform enhancement from an early phase on computed tomography and angiography.
      Right hepatectomy with total caudate lobe resection was performed. Pathological
      examination revealed the tumor to be a primary leiomyoma of the liver, positive
      for smooth muscle actin and desmin on immunohistochemical examination. Primary
      liver leiomyoma is very rare and only 18 cases have been reported to date. The
      clinical features of these cases from the literature are also discussed.

PMID- 16304826
TI  - Orthopedic-driven ambulatory surgery centers and specialty hospitals--a physician
      and hospital perspective.
AB  - This article provides an overview of several issues facing the orthopedic-driven
      ambulatory surgery center and specialty hospital development industry. The
      article specifically then reviews certain key business drivers to industry
      growth, examines key risks related to ASC and specialty hospital projects, and
      provides a brief review of certain legal issues related to the same.

PMID- 16304827
TI  - [Why can an article be and must be short?].

PMID- 16304828
TI  - [The answers to the questions. The difficult academic and professional
      equilibrium in pre-European Spain].
AB  - After the sweep of the three preceding articles, the author responds to the
      questions posed in the first article, concluding that a turn towards a practical
      reflexive position can, over the medium term, solve the tensions which the
      positivist conceptions have created between knowledge and professional action. A
      bibliography for all four articles is included.

PMID- 16304829
TI  - [The foot in diabetes].
AB  - Nursing was qualified to carry out an in depth study on the effects diabetes has
      on feet by means of an educational intervention complemented by a pre- and post
      intervention transversal study 268 primary care center nurses who deal with
      diabetics in 34 basic health areas participated in this study This project was
      sponsored by SALUD, the Aragon Health service, in 2000 and it lasted two years.
      This study was presented at the XI FEAED (Spanish Federation of Associations of
      Educators in Diabetes) Congress which took place in Valencia in 2004.

PMID- 16304830
TI  - [Peripheral venous catheters: incidence of phlebitis and its determining
      factors].
AB  - To determine the rate of phlebitis cases and their risk factors, the authors
      carried out a prospective follow-up study in an internal medicine unit. 553
      catheters pertaining to 266 patients were analyzed. The length of time a catheter
      was used did not have any significant bearing on the development of phlebitis.
      The rate of phlebitis cases was more frequent when medication was infused at
      intermittent intervals. The use of intravenous antibiotics significantly
      increased the risk of phlebitis when compared to the administration of other
      types of medication.

PMID- 16304831
TI  - [Surgical instruments (III). A classification of surgical instruments based on
      their physical traits].
AB  - In order to help professionals learn, understand and especially to remember the
      qualities of surgical instruments, in this article the author presents a study
      based on the physical traits of surgical instruments.

PMID- 16304832
TI  - [The emotional impact of a hospital].
AB  - In light of the challenge to offer future nurses a quality university education,
      the authors identify and evaluate the diverse activities which nurses carry out
      during their clinical stays, which cause a major emotional impact; therefore,
      these require greater attention, more knowledge and psychological resources which
      will aid them to successfully comply with this important aspect of their careers.
      With this goal in mind, the authors complied an inventory of specific stress
      factors for our context which was applied to a sample of 87 students at the
      school of nursing in Melilla. The results enabled the authors to establish a
      hierarchal order among the clinical experiences evaluated as having a greater
      stress load. These are those experiences, in descending order: terminal phase
      patients and death, tolerating external suffering, and hospital environment
      followed by oncology patients, psychiatric patients, tolerating aggressiveness,
      and infectious diseases. In light of the results, the authors offer some
      suggestions for the design of an operational program which shall mitigate and
      prevent as is possible the emotional impact of stress caused by clinical
      experiences.

PMID- 16304833
TI  - [Prevention is the law of life].

PMID- 16304834
TI  - [Drugs, a current problem].
AB  - The author analyses what addiction to drugs consists of and how this addiction
      develops. The author also sketches some of the difficulties. Which occur in
      dealing with drug addictions.

PMID- 16304835
TI  - [Stories by the elderly].
AB  - This Brazilian article bears interest for its qualitative methodology which
      allows us to get a feeling for the elderly of this country being able to relate
      the results of their lives and knowledge to our own. The lack of an educational
      health program for the elderly led the authors to create the Health Care Group
      for the Elderly (GRASI in Portuguese) in which we developed an educational
      program based on the social-historical perspective of L. S. Vygotsky. This
      current study analyzes the dynamic speeches recorded by a group of elderly in the
      GRASI educational program. A group of seven elderly people, from both sexes,
      having an age equal to or greater than 60, participated in an analysis of the
      content from meetings among themselves. To analyze the data obtained, in the
      underlying text as well as their recorded speech, the feelings and meanings of
      their conversations and stories were identified and separated into thematic
      units. The results obtained reveal that the opportunity to express their
      experiences regarding the transformation the elderly have lived during their
      lives, and to find new ways to treat health problems or how to carry out self
      health care, is an important resource for elderly nursing care which can lead to
      the development of health education programs.

PMID- 16304836
TI  - [Electroconvulsive therapy (ECT)].

PMID- 16304837
TI  - Proteomic analysis on multi-drug resistant cells HL-60/DOX of acute myeloblastic
      leukemia.
AB  - Multi-drug resistance (MDR) is an important factor that causes treatment failure
      in acute leukemia. However, the full development mechanisms of MDR still await
      [corrected] investigation. The purpose of this study is to investigate
      differentially expressed proteins in the multi-drug resistant acute myeloblastic
      leukemia (AML) cell line HL-60/DOX and the drug sensitive cell line HL-60, and to
      identify new potential multi-drug resistant related molecules with the proteomic
      approach. Two-dimensional gel electrophoresis (2-DE) maps of the proteins,
      extracted from two AML cell lines, HL-60/DOX and HL-60, were established
      respectively. The extracted proteins were digested by enzymes and identified with
      the matrix assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS). The data of the peptide mass fingerprinting (PMF) was matched
      with databases of proteomics available on the Internet. Results showed that 16
      proteins were identified to be differentially expressed between HL-60/DOX and HL
      60 cells. They involved the protein disulfide isomerase precursor (PDI), the
      proteasomes alpha1 and other proteins which are related to drug resistance or
      cell metabolism, but their functional significances are required further
      investigation. Nevertheless, it is clear that this proteomic approach for studing
      the biology and development of MDR is a prerequisite in leukemia.

PMID- 16304838
TI  - Effects of parathyroid hormone on plasma zinc concentration in rat with chronic
      renal failure.
AB  - Although both secondary hyperparathyroidism (HPT) and hypozincemia are commonly
      observed in humans and animals with chronic renal failure (CRF), the relationship
      between secondary HPT and hypozincemia is little delineated. The present study
      was designed to examine whether the elevated plasma parathyroid hormones (PTH)
      levels do affect the disposition of extrarenal zinc and decrease plasma zinc
      level in CRF rats. The experiment was performed in normal and CRF rats with
      intact parathyroid gland and parathyroidectomized (PTX), using an acute zinc load
      alone or in combination with PTH infusion in five groups of rats: normal control,
      CRF control, CRF + PTH, CRF + PTX and CRF + PTX + PTH. Five sixths nephrectomy
      was used to produce CRF. All rats were infused with 0.05 mg/kg/min ZnSO4 alone or
      in combination with 10 microg/kg/min PTH through intravenous infusion for 90 min
      with serial monitoring of plasma zinc levels every 30 min. The alteration of
      plasma interleukin-6 (IL-6) levels and the effect of zinc levels in red blood
      cells (RBCs), as well as the output of bile juice zinc and urinary zinc excretion
      during the 90-min infusion were also examined. After 90-min infusion, liver
      tissue was harvested to determine its contents of zinc and metallothionein (MT).
      During zinc sulfate infusion, the responses of plasma zinc concentration in PTH
      combined infusion groups markedly decreased as compared with those of the non-PTH
      combined infusion groups, especially in the CRF rats with PTX. However, when zinc
      sulfate alone was infused, the response of plasma zinc concentration was found to
      increase in CRF rats with PTX as compared with that of the CRF control rats. PTH
      infusion groups significantly increased the levels of plasma IL-6 (P < 0.05), but
      it did not alter the levels of RBC zinc and the secretion of bile zinc during the
      90-min infusion. After 90-min zinc sulfate infusion, higher liver zinc and MT
      contents were found in CRF control, CRF + PTH and CRF + PTX + PTH rats, but were
      [corrected] not found in the CRF + PTX rats. Zinc sulfate infused alone was found
      to increase the excretion of basal zinc in bile juice and urine, in both normal
      and CRF rats. The percentage of zinc load translocated out from the plasma during
      90-min zinc sulfate infusion significantly rises in CRF rats and CRF rats with
      PTH-combined infusion as compared with normal control rats. However, in CRF rats
      with PTX, the percentage of zinc load translocated out from plasma during 90-min
      zinc sulfate infusion was similar to that in the normal control rats. Therefore,
      we suggested that in CRF rats, the excessive secretion of PTH may play a role in
      the pathogenesis of hypozincemia because PTH enhanced extrarenal zinc disposal.

PMID- 16304839
TI  - Implication of nNOS in the enlargement of AChR aggregates but not the initial
      aggregate formation in a novel coculture model.
AB  - The aggregation of nicotinic acetylcholine receptors (AChRs) is an early hallmark
      of the formation of neuromuscular junction (NMJ), and nitric oxide is recently
      known to play an important role. In many NMJ studies, nerve-muscle coculture
      model was used, and NG108-15 cells, a neuroblastoma x glioma hybrid cell line,
      were the most frequently used nerve cells. However, possible contributions from
      glial cells could not be excluded. In this study, Neuro-2a neuroblastoma cells
      were used instead of [corrected] coculture with myotubes, and the relationship
      between AChR aggregation and spatiotemporal expression and activation of nNOS
      (neuronal nitric oxide synthase) was examined. Upon coculture, AChR aggregates
      were observed by FITC-conjugated alpha-bungarotoxin, and double labeling of AChRs
      and neurofilament showed that the neurites of a Neuro-2a cell innervated several
      myotubes. After treating the cocultures with single dose of L-NAME at the end of
      1-day [corrected] coculturing, only slight effect on AChR aggregation could be
      found indicating that nNOS is not related to the initial formation of AChR
      aggregates. In contrast, when L-NAME treatment was given at the end of a 3-day
      coculturing, the day just before reaching the maximum extent of AChR aggregation,
      new AChR aggregates were hardly formed and the preformed AChR aggregates were
      even dispersed indicating that the enlargement of AChR aggregates is highly
      dependent on the nNOS activity. Double-labeling study of nNOS and AChR further
      showed that the coupling of membranous nNOS to regions nearby the AChR aggregates
      was essential for the enlargement of AChR aggregates. These results not only
      revealed the spatiotemporal relationship between AChR aggregation and nNOS
      activity but also verified the feasibility and usefulness of using Neuro-2a cells
      in a coculture model.

PMID- 16304840
TI  - Expression of protein kinase C alpha in biopsies and surgical specimens of human
      hepatocellular carcinoma.
AB  - Variations in the activity of protein kinase C (PKC) have been observed in
      different types of tumors. Although these inconsistent findings may be attributed
      to the alterations of individual PKC isoforms, the effects of general anesthetic
      may not be neglected. In this study, biopsies and surgical specimens were
      obtained from patients with HCC, and the levels of PKCalpha were analyzed by
      immunohistochemistry. PKCalpha expression in biopsies was mainly revealed on the
      cell membrane of hepatocytes whereas that in the surgical specimens was in the
      cytosol and on the membrane. In both types of specimens, the PKCalpha level in
      HCC was significantly higher than that in the adjacent non-tumorous tissue.
      Moreover, the level of PKCalpha in biopsies was significantly higher than that in
      surgical specimens of the corresponding tissue type. These findings suggested
      that general anesthetics may significantly affect the expression of PKCalpha, and
      the effects of anesthetics should not be neglected in observations which were
      made only based on surgical specimens.

PMID- 16304841
TI  - Activation of ventrolateral medulla neurons by arginine vasopressin via V1A
      receptors produces inhibition on respiratory-related hypoglossal nerve discharge
      in the rat.
AB  - Arginine vasopressin (AVP) is an important neurohormone in the regulation of many
      aspects of central nervous system, yet its modulation on the respiratory function
      remains largely unknown. The aims of this study were to investigate the
      modulation of phrenic (PNA) and hypoglossal nerve activity (HNA) by central
      administration of AVP and to identify the involvement of AVP V1A receptors in
      this modulation. Animals were anesthetized with urethane (1.2 g/kg, i.p.),
      paralyzed with gallamine triethiodide (5 mg/kg, i.v.), and artificially
      ventilated. The rat was then placed on a stereotaxic apparatus in a prone
      position. PNA and HNA were monitored at normocapnia in hyperoxia. Microinjection
      of AVP into the medial ventrolateral medulla (VLM) and/or rostral ventral
      respiratory group (rVRG) produced a dose-dependent inhibition on both PNA and
      HNA, whereas the microinjection of AVP into the region of lateral VLM resulted in
      a similar inhibition of these nerve activities and a pressor response. Systemic
      administration of phentolamine abolished the pressor effect but did not affect
      the inhibition of PNA and HNA evoked by AVP injection into the lateral VLM and/or
      rVRG, suggesting that AVP-induced inhibition of PNA and HNA was not due to the
      side effect of pressor response. These cardiopulmonary modulations were totally
      abolished by the central pretreatment of AVP V1A receptor antagonist. Our results
      suggested that AVP may activate neurons located at the VLM and/or rVRG via the
      AVP V1A receptor to inhibit respiratory-related HNA and thus to regulate upper
      airway aperture.

PMID- 16304842
TI  - Computer simulation of the reentrant cardiac arrhythmias in ischemic myocardium.
AB  - Computer simulation was performed to determine how reentrant activity could occur
      due to the spatial heterogeneity in refractoriness induced by the regional
      ischemia. Two regional ischemic models were developed by decreasing the
      intracellular ATP concentration, reducing conductance of the inward Na+ current
      and increasing the extracellular K+ concentration on the two-dimensional sheet.
      Operator splitting method was used to integrate the models. The vulnerability to
      reentry was estimated from the timings of premature stimuli on the constructed
      models, which could result in unidirectionally propagating action potentials. Two
      kinds of sustained spiral waves and their Pseudo-Electroscardiograms were
      observed in numerical simulation. The results showed that the dispersion of
      refractory period increased with ischemic aggravation, and led to augment of the
      vulnerable window. A permature stimulation within the vulnerable window could
      easily induce spiral reentry. The Pseudo-Electrocardiograms of the spiral waves
      exhibited monomorphic tachycardiac waveforms. Thus, the spatial heterogeneity in
      refractoriness could be a substrate for reentrant ventricular tachyarrhythmias on
      the regional ischemic tissue.

PMID- 16304843
TI  - Identification of androgen-responsive element ARE and Sp1 element in the maspin
      promoter.
AB  - Maspin is a serine protease inhibitor (serpin) with tumor-suppressing function in
      mammary gland. It is down-regulated in primary prostate cancer cells and lost in
      metastatic cells. To better understand the transcriptional regulation of maspin
      gene, the 860bp (-765 approximately +95) of its promoter sequence was amplified
      by PCR from the human genomic DNA. Then this 860bp sequence and a series of
      deletions from 5' and 3' ends were inserted into the upstream of luciferase
      reporter gene respectively. Results from dual luciferase reporter assay and
      electrophoretic mobility shift assay indicated that there were a negative
      androgen-responsive element (ARE) in the region of -277 to -262 and a positive
      Sp1 element in the region of +14 to +35, respectively. In addition, androgen
      receptor (AR) can recognize and bind to the ARE element, and then inhibit the
      activity of maspin promoter.

PMID- 16304844
TI  - Control of lead poisoning in Pakistan.

PMID- 16304845
TI  - Effect of environmental lead pollution on blood lead levels in traffic police
      constables in Islamabad, Pakistan.
AB  - OBJECTIVE: To determine the blood lead levels and trace elements (copper and
      manganese) in traffic police constables in Islamabad in order to assess the
      effects of environmental pollution on the levels of metals in body fluids.
      METHODS: Blood samples were collected from 47 male traffic police constables, 21
      to 45 years of age, posted in different areas of Islamabad and controlling
      traffic from 3 months to 18 years, 8 hours/day, 6 days/week. Adolescent males (13
      19 years), residing in comparatively clean and very low traffic areas were
      included as controls. Blood lead, copper, and manganese concentrations were
      estimated by atomic absorption spectrophotometry. RESULTS: The mean blood lead
      level among constables (27.27 microg/dl) was significantly (p<0.0001) high as
      compared to controls (3.22 microg/dl). Twenty one percent constables had elevated
      blood lead levels (over 25 microg/dl) and 13% had levels above the safety limit
      (40 microg/dl). No correlation was found between blood lead levels and length of
      service. No significant difference was found in the mean values for copper
      between traffic constables (93.49 microg/dl) and controls (71.15 microg/dl). The
      mean blood manganese levels in traffic constables (21.94 microg/dl) were
      significantly (p<0.0001) higher than in controls (1.70 microg/dl). The mean blood
      lead levels were significantly high in traffic constables of Karachi (47.7
      microg/dl) as compared to Islamabad (27.2 microg/dl), which shows direct relation
      of rise in blood lead levels with vehicle exhaust. CONCLUSION: Environmental lead
      pollution is associated with an increased blood lead concentration in those who
      are regularly exposed to vehicle exhaust in high traffic areas. The degree of
      lead pollution arising from vehicle exhaust differs in Karachi and Islamabad.
      Exposure to air containing dust particles rich in manganese may affect blood
      manganese levels.

PMID- 16304846
TI  - Tubercular ureteric strictures.
AB  - OBJECTIVE: To review the presentation of tubercular ureteric strictures and
      assesses the role of balloon dilatation and open surgical repair in their
      management. METHODS: This was a retrospective review of tubercular ureteric
      strictures managed between January 1993 and December 2002. The records were
      analyzed to assess clinical presentation and compare the results of balloon
      dilatation with open surgical repair. Success was defined as adequate drainage on
      imaging, no worsening of renal function, no recurrence of symptoms and no
      requirement of intervention on further follow up. The long term success rates
      were compared using the t-test for proportion. RESULTS: Of 73 strictures, 88% had
      lower urinary tract symptoms. Genital abnormalities suggestive of tuberculosis
      was observed in 40% male patients. Urine examination yielded aseptic pyuria in
      85%, positive AFB smears in 36% and positive AFB cultures in 32%. A small
      capacity bladder and non-functioning renal units were the only consistent
      findings on intravenous urogram. Nephrectomy was performed in 37% cases due to
      non salvageable kidneys at presentation. The success rate of stenting fell from
      93% on immediate follow up to 59% on a follow-up of 12 months. At 90% success
      rates on a follow-up of 7 months open surgical repair was superior (p 0.03). Long
      term success following balloon dilatation in renal units with good function was
      78% compared to 25% for poorly functioning units. (p= 0.01) CONCLUSION: Open
      surgical repair is superior to balloon dilatation in the management of tubercular
      ureteric strictures. Renal function may predict the success of balloon
      dilatation.

PMID- 16304847
TI  - Evaluation and outcome of pregnancy complicated by heart disease.
AB  - OBJECTIVE: To assess the maternal and fetal outcome in pregnancies associated
      with maternal heart disease. METHODS: The study included 50 pregnant cardiac
      patients from the Department of Obstetrics and Gynaecology Unit-I Nishtar
      Hospital, Multan. Age, parity, type of cardiac lesions, class of disease,
      specific treatment given, obstetric and cardiac complications, maternal and fetal
      outcome were analyzed. RESULTS: Out of 5100 obstetric patients, 50 cases of heart
      disease were diagnosed, giving a frequency of 0.98%. The ages of the women ranged
      between 26-35 years (64%) and 52% were multigravida. Congenital Heart Disease
      (CHD) was present in 28% cases and 66% had Rheumatic Heart Disease (RHD) and
      mitral stenosis which was the dominant lesion. Anticoagulation was given to 3
      (6%) cases, Digoxin was required in 20 (40%) cases, Diuretics 18 (36%) while
      antihypertensive and beta blockers were given to 4 (8%) cases each, whereas
      prophylactic antibiotic was given to all (100%) patients. Congestive Cardiac
      Failure (CCF) was seen in 10 (20%) cases, infective endocarditis and
      thromboembolism in one (2%) case each. Maternal mortality occurred in one (2%)
      case and one (2%) neonatal death was encountered. Cardiomyopathy was seen in 2
      (4%) cases. Vaginal delivery was had in 91.49% women and 80% were term
      pregnancies. Preterm deliveries were 14% and 42.55% babies were of low birth
      weight. CONCLUSION: Although, heart disease is rare among pregnant women, it
      needs to be carefully managed in a tertiary care setting by a team of
      obstetrician, cardiologist and anaesthesiologist, to obtain good maternal and
      foetal outcome.

PMID- 16304848
TI  - Iron deficient children and significance of serum ferritin.
AB  - OBJECTIVE: To evaluate the significance of serum ferritin in iron deficiency
      anaemia as compared to other indices. METHODS: Children were selected as anaemic
      and non-anaemic on the basis of hemoglobin (10g/dl) and transferrin saturation
      (15%). Red cell morphology, hemoglobin, serum iron, TIBC, transferrin saturation
      and serum ferritin were determined. RESULTS: Red cell morphology was of little
      significance. Haemoglobin, serum iron, transferrin saturation and serum ferritrin
      were all lower in children. A positive correlation of serum ferritin with age,
      haemoglobin, serum iron and transferrin saturation and a negative correlation
      with TIBC was found. CONCLUSION: Serum ferritin was more sensitive indicator as
      compared to serum iron, TIBC, and transferrin saturation.

PMID- 16304849
TI  - Graft versus host disease in allogeneic stem cell transplantation--3 1/2 years
      experience.
AB  - OBJECTIVE: To evaluate the frequency and outcome of graft versus host disease
      after allogeneic stem cell transplant in haematological disorders at Armed Forces
      Bone Marrow Transplant Centre, Rawalpindi from July 2001 to December 2004.
      METHODS: Eighty-six patients with various haematological disorders namely
      aplastic anaemia (n=32), b-Thalassaemia (n=25), CML (n=22), ALL (n=3), AML (n=1)
      Fanconi's anaemia (n=2), and Gaucher's disease (n=1), underwent allogeneic stem
      cell transplantation. All patients received cyclosoprin, prednisolone and short
      course of methotrexate as GvHD prophylaxis. The patients who developed acute GvHD
      > grade-II or chronic extensive GvHD received steroids at a starting dose of 2
      mg/kg body weight along with gradual increase in cyclosporine dosage (max dose
      12.5 mg/kg). RESULTS: The overall incidence of acute GvHD grade-II to IV was
      44.2% (n=38/86) where as the incidence of chronic extensive GvHD was 14%
      (n=12/86). Acute GvHD was 68% (n=17/25) in beta-Thalassaemia, 50% (n=11/22) in
      CML, 50% (n=2/4) in Acute Leukaemias and 25% (n=8/32) in Aplastic Anaemia.
      Chronic GvHD was 25% (n=1/4) in Acute Leukaemias, 18.8% (n=6/32) in Aplastic
      Anaemia, 18.2% (n=4/22) in CML and 4% (n=1/25) in beta-Thalassaemia. The overall
      survival in acute GvHD was 84.2% (n=32) where as the overall survival in chronic
      GvHD was 50% (n=6). The overall mortality in acute GvHD was 15.8% (n=6) and 50%
      in chronic GvHD (n=6). CONCLUSION: The morbidity and mortality due to severe
      acute and chronic GvHD remains high despite standard prophylaxis against GvHD.
      New strategies are needed to prevent and treat GvHD.

PMID- 16304850
TI  - Assessment of proteinuria by using protein: creatinine index in random urine
      sample.
AB  - OBJECTIVE: To assess the quantitative measurement of proteinuria by using random
      urine protein:creatinine index/ratio in comparison with 24 hours urinary protein
      excretion in patients of renal diseases having normal glomerular filtration rate.
      METHODS: One hundred and thirty patients, 94 males and 36 females, with an age
      range of 5 to 60 years; having proteinuria of more than 150 mg/day were included
      in this study. Qualitative urinary protein estimation was done on random urine
      specimen by dipstick. Quantitative measurement of protein in the random and 24
      hours urine specimens were carried out by a method based on the formation of a
      red complex of protein with pyrogallal red in acid medium on Micro lab 200
      (Merck). Estimation of creatinine was done on Selectra -2 (Merck) by Jaffe's
      reaction. The urine protein:creatinine index and ratio were calculated by
      dividing the urine protein concentration (mg/L) by urine creatinine concentration
      (mmol/L) multilplied by 10 and mg/mg respectively. RESULTS: The
      protein:creatinine index and ratio of more than 140 and 0.18 respectively in a
      random urine sample indicated pathological proteinuria. An excellent correlation
      (r=0.96) was found between random urine protein:creatinine index/ratio and
      standard 24 hours urinary protein excretion in these patients (p<.001). Dipsticks
      showed moderate correlation (r=0.52) and error in interpretation of proteinuria.
      CONCLUSION: The protein:creatinine index in random urine is a convenient, quick
      and reliable method of estimation of proteinuria as compared to 24 hours of
      urinary protein excretion for diagnosis and monitoring of renal diseases in our
      medical setup.

PMID- 16304851
TI  - Role of computed tomography in acute pancreatitis and its complications among age
      groups.
AB  - OBJECTIVE: To determine value of CT scan in diagnosis of acute pancreatitis, its
      complications and to correlate with severity among different age groups. METHODS:
      The study was carried out from August 2001 to August 2002 at the Radiology
      Department, Aga Khan University Hospital. A total of 40 patients (33 male and 7
      female) with age range from 16-71 years were divided in three groups. Group I was
      less than 40 years (12 patients), Group II was between 40-60 years (17 patients),
      and Group III was more than 60 years (11 patients). CT scans were assessed for
      pancreatic necrosis and its complications. CT Severity Index (CTSI) was
      calculated according to Balthazar's method. RESULTS: In 17 patients with mild
      pancreatitis, 5 had necrosis involving one-third of pancreas. In 13 patients with
      severe pancreatitis, 8 had necrosis involving more than half of the pancreas and
      5 had necrosis involving half of the pancreas. No significant correlation was
      demonstrated between moderate pancreatitis and degree of necrosis. Thirty
      patients had complications, 8 had mild CTSI, 9 had moderate CTSI and 13 patients
      had severe CTSI. CONCLUSION: The study demonstrated a relationship between CTSI
      and severity of pancreatic damage and incidence of complications.

PMID- 16304852
TI  - Frequency and sensitivity pattern of Extended Spectrum beta Lactamase producing
      isolates in a tertiary care hospital laboratory of Pakistan.
AB  - OBJECTIVE: To determine frequency, distribution and sensitivity pattern of
      Extended-Spectrum beta Lactamase (EBSL) producing organism at a tertiary care
      hospital in Pakistan. METHODS: All members of enterobacteriacae isolated between
      April and August 2002 were studied. Isolates were speciated according to standard
      biochemical tests. Susceptibility testing was performed by Kirby-Bauer method.
      ESBL was detected using double disc method using cefotaxime versus cefotaxime
      plus clavulanate according to NCCLS. Statistical analysis was performed by SPSS
      version 10. Test of significance were calculated using chi-square test. RESULTS:
      During the study period, 1137/2840 (40%) of the isolates tested were found to be
      ESBL producing. ESBL positivity was detected in 50% Enterobacter sp., 41% E. coli
      and 36% K. pneumoniae. ESBL production was noted in 52% of nosocomial isolates
      tested (415/799). ESBL was more frequent in patients at the extremes of ages
      (under 5 years and more than 60 years). Cross-resistance to non-beta lactam
      antibiotics (flouoroquinolones, aminoglycosides and co-trimoxazole) was also more
      frequent in ESBL producing organisms (p<0.05). CONCLUSION: A high frequency of
      ESBL positivity amongst our isolates is documented which is alarming in low
      income settings where expensive second line agents are unavailable. Our data
      supports urgent need for regular screening and surveillance for these organisms.

PMID- 16304853
TI  - Indigenous development of antibody screening cell panels at Armed Forces
      Institute of Transfusion (AFIT).
AB  - OBJECTIVE: To prepare good quality screening cells reagent according to the
      standards, at Armed Forces Institute of Transfusion (AFIT). METHODS: Random group
      O donors, seronegative for HBsAg, HCV and HIV were selected if they resided in
      Rawalpindi or Islamabad and could be contacted. Micro column Gel technique was
      used to find out R1R1, R1wr, R2R2 and rr phenotypes with or without K antigen.
      Repeat sample of these donors were phenotyped for minimum antigens required for
      reagent cells. Teams of three donors each were made on the basis of Rh, K
      antigens and homozygosity for E, Fya, Fyb, Jka, Jkb, S, and s antigens. The
      selected cells were added to preservative suspension containing neomycin and
      chloramphenicol and dispensed as 8% solution and labeled. Cells were submitted to
      quality control testing for 35 days shelf life and efficacy was compared with
      commercial cells. RESULTS: The cells of required phenotype were prepared
      according to UK guidelines and AABB standards with minor exceptions. Reagent
      cells had excellent quality confirmed by many quality control procedures and were
      comparable to commercial cells in efficacy. The cost saving was significant.
      CONCLUSION: AFIT can introduce type and screen policy and Maximum Surgical Blood
      Ordering Schedule using indigenously prepared cells, of good quality and at an
      affordable price. This will enhance serological safety of recipients and brings
      AFIT near to adopting standard practice of pretransfusion testing.

PMID- 16304854
TI  - Competency profile of locally manufactured clopidogrel Lowplat and foreign
      manufactured clopidogrel Plavix in patients of suspected ischemic heart disease
      (CLAP-IHD).
AB  - OBJECTIVE: The primary objective of this study was to test the hypothesis that
      the antiplatelet effects of loading dose of locally manufactured clopidogrel
      Lowplat referred as drug (B) 600 mg (8 tablets) given once is comparable to the
      antiplatelet effects of loading dose of foreign manufactured clopidogrel Plavix
      referred as drug (A) 600 mg (8 tablets) given once in patients with suspected
      ischemic heart disease. METHODS: This was a double blind, randomized, cross over,
      study, to compare the safety and efficacy of study drug (B) versus (A) in adult
      subjects suffering from suspected ischemic heart disease presented at National
      Institute of Cardiovascular Disease (NICVD), Karachi. RESULTS: Mean platelet
      aggregation inhibition by drug (B) was 60.7% (p<0.001), while with drug (A) it
      was 57.8% (p<0.001), using 20 micromol/L ADP, which is statistically significant
      and comparable. Clopidogrel 600 mg as loading dose was well tolerated.
      CONCLUSION: Both drugs were equally effective in reducing the platelet
      aggregation. CLAP-IHD confirmed that drug (B) and (A) are equally effective and
      comparable antithrombotics in Pakistani population. The cost benefit of drug (B)
      should be made beneficial to the patients.

PMID- 16304855
TI  - Periodontal infection: a potential risk factor for pre-term delivery of low birth
      weight (PLBW) babies.
AB  - Pre-term delivery of low-birth-weight (PLBW) babies is considered a major peri
      natal problem in many countries and is contributing substantially to infant
      mortality and to childhood handicap. There is a reported incidence of pre-term
      delivery of low-birth-weight (PLBW) babies of 37% of all live births in Pakistan,
      which has a tremendous impact on health care system in this community. The
      prevalence of periodontal disease in Pakistan is also very high in all age groups
      and women of child bearing age (18-34 years) are no exception. Recent studies
      indicate periodontal infection as a potential independent risk factor for PLBW,
      and is considered to be 7 times more likely to be associated than any other risk
      factors. Several postulated mechanisms have been reviewed, including the
      virulence effects and role of asymptomatic bacteraemia, focusing on the bacterial
      load in periodontium facilitating its transmission from oral cavity to the
      uterus. The indication that periodontal disease is a potential risk factor for
      the delivery of PLBW; a high level of periodontal disease in women of child
      bearing age and similar high level of PLBW babies in country, calls for further
      longitudinal investigations that validate a causal relationship between
      periodontal infection and pre-term delivery of LBW babies in Pakistan. A review
      of literature and preliminary communication for a planned study is presented.

PMID- 16304856
TI  - Plasma cell leukemia: case report of a rare and aggressive variant of multiple
      myeloma.
AB  - Plasma cell leukemia (PCL) is a rare disease and is the least common variant of
      multiple myeloma accounting for 2-3% of all plasma cell dyscrasias. We report a
      patient who presented with history of high grade fever, weakness, palpitations,
      loss of appetite, bone pains and mental confusion for twenty days. Initial
      evaluation revealed plasmacytosis with blood plasma cell count of 5184/cumm. His
      hemoglobin (Hb) was 11.3 gm/dl, platelets were 75000/cumm and total leucocyte
      count (TLC) was 21600/cumm (24% plasma cells). Bone marrow examination revealed
      >60% plasmablasts. Serum LDH was high at 3117 U/L and serum calcium was also
      elevated at 13.9 mg/dl. A diagnosis of PCL was made and the patient was started
      on treatment for hypercalcaemia with Melphalan/Prednisolone regime along with
      supportive care. Patient deteriorated very rapidly despite treatment and died on
      the eighth day. A detailed report of this case and a review of PCL is presented
      here.

PMID- 16304857
TI  - Allogeneic peripheral blood stem cell transplant (PBSCT) using anti-IL2 receptor
      antibody Daclizumab for the prevention of acute graft versus host disease in
      steroid refractory Diamond Blackfan anaemia: a case report.
AB  - The case report of a 2 year old boy with steroid refractory DBA, treated with
      allogeneic PBSCT from an HLA matched sibling is presented. Anti-IL2 receptor
      antibody Daclizumab was used as a prophylaxis for graft versus host disease
      (GvHD). Complete recovery without any evidence of GvHD ensued.

PMID- 16304858
TI  - Vein of Galen aneurysm: antenatal diagnosis: a case report.
AB  - Aneurysm of vein of Galen is a rare congenital malformation with reported
      incidence of less than 1% of cerebral vascular malformations. Most cases present
      in neonatal life with congestive cardiac failure. We report a case of aneurysm of
      vein of Galen diagnosed in intrauterine life at 36 weeks of gestation. The
      importance of third trimester Doppler ultrasound is highlighted.

PMID- 16304859
TI  - Project mentality: a threat to effective implementation and sustainability of
      donor funded projects in Pakistan.

PMID- 16304860
TI  - Latest approaches to the diagnosis and management of food allergies in children.
AB  - Adverse food reactions are a challenge for physicians. As the prevalence of this
      condition rises, it is important that paediatricians and other health care
      professionals adeptly diagnose this condition. We begin by discussing the
      relevant points in history and physical examination, then we discuss the recent
      effective diagnostic tests and techniques available for doctors and patients,
      along with several management options. Over the last decade, there have been
      major advancements in this field and novel mechanisms have been proposed which
      efficiently modulate immune mechanisms involved. Although results are only
      preliminary, they do however, indicate a promising future for patients with food
      allergies.

PMID- 16304861
TI  - Maintaining health information system at healthcare institutions: a need of the
      day.

PMID- 16304862
TI  - Graft versus host disease.

PMID- 16304863
TI  - Leishmaniasis--an impending epidemic.

PMID- 16304864
TI  - Survival and graft versus host disease in first 100 patients undergoing
      allogeneic peripheral blood stem cell transplantation: a single centre
      experience.
AB  - OBJECTIVE: To present the survival and evaluate the demographic characteristics
      as risk factors for acute and chronic graft versus host disease (GvHD) in 100
      recipients of HLA identical related allogeneic peripheral blood stem cell
      transplantation. METHODS: Indications for transplant were non-malignant and
      malignant haematological disorders. Bu/Cy conditioning was given for
      haematological malignancies and beta-Thalassaemia major, Cyclophosphamide was
      given in aplastic anaemia. GvHD prophylaxis was Cyclosporin and Methotrexate. The
      patients received a median nucleated cell dose of 7.93 10(8)/kg. RESULTS: Of 100
      recipients, 72 were males and 28 females. Median age was 13.5 years (range 1.5
      44). There were 65 male and 35 female donors. Median age was 15 years (range 4
      45). Grade-I aGvHD was noted in 18 (18%), Grades-II in 6 (6%), Grade-III in 3
      (3%) while Grade-IV in 1 (1%) patients. Diagnosis was found to be a significant
      risk factor for aGvHD. Kaplan Meyer analysis showed that malignancy, aGvHD,
      recipients above 14 years of age, female patients and engraftment after 12 days
      were associated with poor outcome. Of 78 patients alive beyond 100 days, 19 (24%)
      developed cGvHD. Mean follow up was 466 days (range 30-1766). Median survival of
      this cohort of patients was 338 days (mean 479 days, 95% CI 72 - 729).
      CONCLUSION: Incidence of acute and chronic GvHD was similar to published data.
      Grade of aGvHD, extent of cGvHD, female patients and haematological malignancies
      were associated with higher rate of aGvHD and a worse outcome.

PMID- 16304865
TI  - Childhood visceral leishmaniasis in Muzaffarabad, Azad Jammu and Kashmir:
      frequency and response to treatment in 61 cases.
AB  - OBJECTIVE: To study the epidemiology and status of resistance to antimonial
      compounds of paediatric hospital population with visceral leishmaniasis in
      Muzaffarabad, Azad Jammu and Kashmir, Pakistan. METHODS: Children admitted
      between January to December 1999 in Azad Kashmir Combined Military Hospital
      Muzaffarabad and diagnosed as Visceral Leishmaniasis by demonstration of
      Leishmania parasites in bone marrow aspirate were included in the study. Patients
      received meglumine antimoniate for 21 days. The demographic information and time
      taken for resolution of fever after initiation of treatment were recorded.
      RESULTS: During study period out of 3520 paediatric admissions, 61 patients had
      visceral leishmaniasis. The frequency of disease was 1.73%. Median age of the
      patients was 18 months. Eighty two percent cases reported during non-winter
      seasons. Fifty nine (96.7%) patients responded to treatment with antimonial
      compounds. Median time taken for resolution of fever was 5.7 days. Two of the
      patients died during the study period. CONCLUSION: Childhood visceral
      leishmaniasis is common in Muzaffarabad and there is no resistance to antimonial
      compounds.

PMID- 16304866
TI  - Allogeneic stem cell transplantation in chronic myeloid leukaemia--2 1/2 year
      experience.
AB  - OBJECTIVE: To evaluate out come of allogeneic Stem Cell Transplantation (SCT) in
      chronic myeloid leukaemia (CMC) at Armed Forces Bone Marrow Transplant Centre,
      Rawalpindi from April 2002 to October 2004. METHODS: Twenty-two patients with CML
      underwent allogeneic SCT from HLA matched siblings. Patients were divided into
      standard (n=14) and high-risk (n=8) groups. Patients were subjected to
      conditioning regimens consisting of Busulphan and Cyclophosphamide. Cyclosporin,
      Prednisolone and Methotrexate were given for GvHD prophylaxis. All donors were
      subjected to PBSC harvest after G-CSF therapy for five days. All received G-CSF
      from Day+5 until ANC >0.5 x 10(9)/l. RESULTS: The median age of the patients was
      29 years (range 7-53 years) with a male to female ratio of 6.3:1. Engraftment was
      achieved in all patients. Median time to achieve neutrophil (ANC 0.5 x 10(9)/l)
      and platelet (20 x 10(9)/l) recovery was 13 days and 12 days respectively. Median
      stay in hospital was 18 days. Acute GvHD (Grade-II-IV) was observed in eleven
      patients (50%) while chronic GvHD was seen in four patients (18%). One patient
      relapsed 8 months post transplant. Two patients (9%) developed Veno-occlusive
      disease (VOD) liver. One patient had haemorrhagic cystitis. Four patients (18%)
      had post transplant infectious complications, which included pseudomonas
      septicemia, aspergillosis, tuberculous pleural effusion and herpes zoster.
      Overall mortality was 22.7% (n=5). The major causes of mortality were VOD liver,
      GvHD grade IV, Pseudomonas septicaemia and aspergillosis. Overall survival was
      77.2% (n=17) and disease free survival was (n=16) 72.7%. Follow up ranges were
      from 23 to 828 days (median 212 days). CONCLUSION: The preliminary results of SCT
      in this small series of patients with CML are very encouraging. To improve the
      long-term survival it is imperative that patients are transplanted early after
      diagnosis and conditioning regimens are selected carefully.

PMID- 16304867
TI  - Colorectal carcinoma, extent and spread in our population. Resection specimens
      give valuable information.
AB  - OBJECTIVE: To acquire information about the extent and spread of colorectal
      carcinomas in our population by examining colon and colorectum resection
      specimens received. METHODS: All colon and colorectum resection specimens
      received in the section of Histopathology, Aga Khan University Hospital, Karachi
      from January 1, 2003 to July 31, 2003 were included in the study. RESULTS: Eighty
      five resection specimens were received during the study period, 69.41% patients
      were males, and 30.59% were females. The mean age for males was 49 years and for
      females 48 years. Tumor location was in left colon (58.82%), and in right colon
      (41.18%). The average size of the lesions in largest dimension was 5.5cms.
      Majority (83.53%) were colorectal adenocarcinomas, 71.76% cases were grade 11,
      16.47% were grade I, and 11.76% were grade III. Most cases (85.88%) infiltrated
      full thickness of the bowel wall extending into the pericolonic fat. Vascular
      invasion was seen in 16.47% cases. Radial margin was positive in 23.08% of rectal
      carcinomas and 57.65% cases showed lymph node metastases. CONCLUSION: The
      findings in our study demonstrate that the disease is usually very advanced with
      extension into pericolonic fat and positive lymph nodes. Thus, the early
      detection and resection (while the disease is still in an early stage) are
      essential in our population using better surgical techniques, for proper staging
      of these tumors.

PMID- 16304868
TI  - Menstrual irregularities with excessive blood loss: a clinico-pathological
      correlation.
AB  - OBJECTIVE: To evaluate various histo-pathological features in endometrial
      curettings of patients complaining of menstrual irregularities with excessive
      blood loss and correlating them with clinical presentations. METHODS: A total of
      260 endometrial curettings were obtained by Dilatation and Curettage done at the
      Department of Gynecology and Obstetrics, Railway Hospital, Rawalpindi. All the
      preserved specimens were processed under standard conditions at the Pathology
      Department, Islamic International Medical College (IIMC). The sections were
      studied after staining with Haematoxylin and Eosin stain. RESULTS: The patients
      presented with menorrhagia in 51.9%, metrorrhagia in 35.4%, polymenorrhoea in
      9.2% and polymenorrhagia in 3.5% cases. History of hormonal intake was observed
      in 0.66% patients. Menstrual disorders were most common in 41-50 years age group
      accounting for 48% cases. Pathology was diagnosed in 40% of endometrial biopsies.
      The endometrial lesions included endometrial hyperplasia (24.7%), chronic
      nonspecific endometritis (13%), endometrial polyp (1.2%), pill pattern
      endometrium (2.3%) atrophic endometrium (0.8%) menopausal pattern endometrium,
      squamous metaplasia, squamous cell carcinoma and chorioncarcinoma (0.4% each).
      CONCLUSION: The dilatation and curettage was found to be an appropriate approach
      with a good diagnostic yield. Fortunately frequency of endometrial malignancy
      appeared to be very low. Endometrial hyperplasia was the leading causes of
      excessive menstrual bleeding.

PMID- 16304869
TI  - The frequency of urinary symptoms in women attending gynaecology clinics at the
      Aga Khan University Hospital Karachi, Pakistan.
AB  - OBJECTIVE: To determine the frequency of urinary symptoms in women attending
      Gynecology clinics at Aga Khan University Hospital, Karachi. METHODS: A total of
      186 women attending the gynaecology clinics for symptoms of menstrual disorders,
      vaginal discharge or uterovaginal prolapse were asked to fill the survey
      questionnaire which included all the details about lower urinary tract symptoms
      (LUTS). RESULTS: Of the 180 women, 82.8% were aged between 15-44 years with BMI >
      or = 25. Culture confirmed recurrent urinary tract infection (at least 3 episodes
      of urinary tract infections evidenced by positive urine culture or treated by
      repeated use of antibiotics) was reported by 32 (17.2%) women. The frequency of
      urinary incontinence was 44.4% with 17.2% cases having stress urinary
      incontinence (SUI). Symptoms of urinary tract infection were not significantly
      affected by age, parity and mode of delivery. Parity was strongly associated with
      prevalence of SUI (F=10.48, P<0.001). Both urge and mixed incontinence were
      significantly related to age (F=20.57, P, 0.001 and F=13.88, P<0.001) but were
      not affected by parity and mode of delivery. CONCLUSION: The high frequency of
      urinary symptoms in our community demands a need for more extensive
      epidemiological study and a specialized unit to provide awareness, treatment and
      training in this area.

PMID- 16304870
TI  - Characteristics of patients with Guillain Barre Syndrome at a tertiary care
      centre in Pakistan, 1995-2003.
AB  - OBJECTIVE: To study the clinical presentation, hospital course and outcome of
      patients admitted with Guillain Barre Syndrome (GBS) to a tertiary care hospital
      in Karachi, Pakistan. METHODS: The charts of patients conforming to International
      Classification of Diseases (ICD) code 9.0, for GBS, from September 1995 to
      January 2003 were reviewed. Clinical data was recorded on a standardized
      questionnaire, which included patients' age, sex, antecedent events, neurological
      signs and symptoms and ventilation requirement. The hospital course was analyzed,
      including nosocomial infections, therapy given and the functional status of
      patients, using the Rankin scale (0-6). Standard SPSS 11.5 software (Windows) was
      used for data analysis. RESULTS: Thirty-four cases of GBS were admitted to the
      hospital during the study period, with an age range of 3 to 70 years. The mean
      age for disease onset was 35.2 years for female patients, compared to 30 years
      for males; the male/female ratio was 1.6:1.Gastrointestinal infections (12/22,
      54.6%) were the most common antecedent event, followed by upper respiratory tract
      infections (9/22, 40.9%) and skin lesions (1/22, 4.5%). Most patients developed
      GBS within one month of the preceding infection. Cranial nerve abnormalities
      (30/34, 88.2%), autonomic dysfunction (21/34, 61.8%) and respiratory failure
      requiring intubation (19/34, 55.9%) were also common. The median Rankin score of
      patients at admission, and at 30 and 60 days thereafter was 5, 4 and 3.5
      respectively. The in-patient mortality was 1 of 34 (2.4%). CONCLUSION: We found
      that GBS occurred at all ages and was slightly more common in males. Majority of
      patients had an antecedent history of infection and had severe disease on
      presentation. The patients were treated with either plasmapheresis or intravenous
      immunoglobulins and there was no significant difference in outcome in the two
      groups. Despite severe persistent disability, in-hospital mortality was low.

PMID- 16304871
TI  - Gall bladder carcinoma in patients undergoing cholecystectomy for cholelithiasis.
AB  - OBJECTIVE: To determine the proportion and timing for suspecting the diagnosis of
      gall bladder carcinoma in patients undergoing cholecystectomy for cholelithiasis.
      METHODS: A retrospective study conducted at the Aga Khan University Hospital,
      Karachi over a period of six years, included medical records of patients, with
      cholecystectomy for cholelithiasis and a histopathological diagnosis of gall
      bladder carcinoma. An extensive review was done with special reference to the
      features of suspected or unsuspected gall bladder carcinoma. Timing of suspicion
      was categorized on the basis of clinical features, investigations, operative and
      histopathological findings. RESULTS: Out of 1396 cholecystectomies performed
      during the period of study, sixteen patients (1.15%) were diagnosed as gall
      bladder carcinoma. Only three patients had pre-operative ultrasonographic
      features to raise suspicion for gall bladder malignancy whereas eight patients
      were suspected to have a malignant lesion, on the operative findings. Five
      patients were missed and the diagnosis was established after histopathological
      examination. CONCLUSION: The ultrasonography can miss a significant number of
      malignant lesions of the gall bladder and every cholecystectomy specimen should
      be examined histologically.

PMID- 16304872
TI  - The magnitude of low bone mineral [corrected] density in middle and old age
      women.
AB  - OBJECTIVE: To describe the frequency of low Bone Mineral Density (BMD) in
      perimenopausal and postmenopausal women. METHODS: Middle to old aged women from
      two teaching hospitals of Peshawar were included in the study. They were divided
      into four age groups, 40-49 years, 50-59 years, 60-69 years and 70 years and
      above. There was no history of any drug use for bone loss. BMD was measured at
      the heel by ultrasonography and main outcome measures were in the form of
      baseline T-Scores. RESULTS: Of the 608 women studied, 35.03% were in the age
      group 40-49 years, 34.87% in 50-59 years, 22.7% in 60-69 years and 7.4% were 70
      years or older. Using WHO criteria, 35.36% of women had osteopenia (T-Score-1 to
      2.49) and 12.01% had osteoporosis (T-Square < -2.5). The frequency of decreased
      BMD increased significantly with increasing age (P<0.000). Osteoporosis was
      present in 9.59% in the age group of 40-49 years, and it increased to 36.99% in
      patients aged 60-69 years and 23.29% in age group of 70 years and above. Within a
      single age group the number of women with osteopenia and osteoporosis was
      significantly high e.g. in age group of 70 years and above only 20% of subjects
      had normal BMD whereas 80% had low BMD. CONCLUSION: Almost half of the sample
      population had decreased BMD. Peri and postmenopausal women constitute a high
      risk group for osteoporosis and future fractures.

PMID- 16304873
TI  - Hydrocephalus in children.
AB  - The word "hydrocephalus" is derived from two Greek words: hydro meaning water;
      and cephalus meaning head; also known as "water on the brain". Historically it is
      believed to result from imbalance between CSF production and absorption, with net
      accumulation of fluid in the cranial cavity; characterized by increase in size of
      the cerebral ventricles. It is classified as: Communicating hydrocephalus, in
      which flow is not obstructed, but CSF is inadequately reabsorbed in the
      subarachnoid space and the Non-communicating hydrocephalus or the Obstructive
      type, in which flow of CSF from the ventricles to subarachnoid space is
      obstructed. This type may also be sub-classified into Congenital and Acquired.
      The overall incidence of hydrocephalus is not known. Approximately 55% of all
      hydrocephalus are congenital. The etiology depends upon the age of the child. The
      clinical features are increase in the size of head, with wide anterior
      fontanelle, prominent scalp veins, sun-setting eyes, optic nerve atrophy,
      nystagmus and increased muscle tone in children upto 2 years. Children more than
      2 years may present with these as hydrocephalus progresses; or if the fontanelles
      are closed, head size may be normal. These may present with optic atrophy or
      papilloedema, abnormal hypothalamic functions (short stature or gigantism,
      obesity, delayed puberty, primary amenorrhea or menstrual irregularity and
      diabetes inspidus) and spastic lower limbs. Performance IQ is worse than verbal
      IQ and learning problems are common. The diagnostic procedures include
      measurement of head circumference, Plain X ray of head, Ventriculography,
      Pneumoencephalography, Ultrasonography, Computed Tomography and Magnetic
      Resonance Imaging. The management may be non-surgical and surgical.

PMID- 16304874
TI  - Heterotopic glial tissue in tonsil: a case report.
AB  - We describe a six month old boy with a mass in the left tonsil. It was present
      since birth and was enlarging progressively. It was completely excised.
      Histopathology showed a choristoma of neural origin composed of glial cells-
      astrocytes in a fibrillary background, and a choroid plexus. Immunohistochemistry
      confirmed the findings.

PMID- 16304875
TI  - Dural metastases presenting as an extradural hematoma: a rare presentation.
AB  - We report a case of an elderly man who presented with hemiparesis and plain CT
      scan findings highly suggestive of an extradural hematoma as the underlying
      cause. This patient was later found to have dural metastases secondary to
      bronchogenic carcinoma. Dural metastases are rare, usually presenting as dural
      mass, but may also present as chronic subdural or extradural hematoma on non
      contrast CT scan, leading to an erroneous diagnosis in the unsuspecting.

PMID- 16304876
TI  - Metanephric adenoma: a rare benign renal tumour.
AB  - Metanephric adenoma is a rare benign renal tumour. We are reporting one
      histologically proven such case in a 23 year old male from Afghanistan. He
      presented with severe right flank pain since 3 weeks. Nephrectomy was done and
      histopathology was consistent with the diagnosis of metanephric adenoma. This
      novel renal mass has been reported to have benign clinical course despite its
      symptomatic presentation and large tumour size. There is no distinguishing
      radiological feature with can differentiate it from malignant tumours. So far, a
      uniformly benign clinical course has been associated with Metanephric adenoma,
      but given its relatively recent identification and rarity and the lack of
      clinical, radiographic, or cytologic means to establish a definite diagnosis,
      Metanephric adenoma remains primarily a pathologic diagnosis.

PMID- 16304877
TI  - Use of recombinant factor VIIa for massive postpartum haemhorrage: case series
      and review of literature.
AB  - Recombinant activated factor VII is indicated mainly for the treatment of
      patients with haemophilia inhibitors. It has also been found successful in the
      treatment of platelet disorder Glanzmann's thrombasthenia. Recently, its use in
      trauma patients and in patients with intracereberal haemorrhage has become well
      established. We present three cases of massive post partum haemorrhage treated
      with rFVIIa, following caesarean section. The response of these three patients is
      discussed along with review of literature.

PMID- 16304878
TI  - Quality of health care: an absolute necessity for patient satisfaction.

PMID- 16304879
TI  - An audit of the students' corner of Journal of the Pakistan Medical Association.
AB  - OBJECTIVE: To analyze the pattern of the first author's institutional affiliation
      and the distribution of different article types published in the students' corner
      of the Journal of Pakistan Medical Association. METHODS: This cross-sectional
      study was carried out in July 2005 and analyzed the students' corner (whenever
      present) of the Journal of Pakistan Medical Association from January 1998 to June
      2005. RESULTS: For the 90 issues of the journal in the stipulated period, 96
      articles were published in the students' corner. Original studies 46 (47.9%) were
      the most commonly published article category followed by personal opinion/review
      category (43.8%) and case-reports 8 (8.3%). The number of personal opinion/review
      articles has been steadily decreasing. Students from Aga Khan University
      contributed 74 (77.1%) articles followed by students from Ziauddin Medical
      University 10 (10.4%). Almost 95% of the authors were from private medical
      colleges. Sindh was the location of the first authors institution in 90 (93.8%)
      cases. CONCLUSION: A major chunk of all articles published in the students'
      corner of the Journal of Pakistan Medical Association originates from two private
      medical colleges in Sindh. Efforts must be made to increase student participation
      across the country. This may be done by asking students to begin scientific
      writing by submitting personal opinion articles. Further research is needed to
      assess the status of student research in terms of published output in Pakistan.

PMID- 16304880
TI  - Connecting communities: making inroads to exchange electronic healthcare data at
      the local level.
AB  - Standardizing healthcare information exchange and interoperability--which permits
      the electronic flow of information among medical organizations--could create
      dollar 77.8 billion in annual savings nationally, according to a recent study.
      Many models have emerged at the community and regional levels recently to
      expedite this process. However, the road they follow is new and often lacks
      guidance. This issue looks at how several organizations are progressing and how
      they expect their actions to impact the delivery and quality of care.

PMID- 16304881
TI  - New studies help patients manage their chronic conditions.
AB  - Providing self-management support to patients with chronic conditions contains
      its own set of challenges to healthcare providers. To assist them, the California
      Healthcare Foundation has commissioned three reports that examine tools and
      strategies caregivers can use to help patients improve their health-related
      behaviors and clinical outcomes.

PMID- 16304882
TI  - AMA Trustees adopt pay for performance principles.

PMID- 16304883
TI  - [Corticosteroids and the risk of glaucoma].
AB  - Corticosteroids are used to treat many diseases and are prescribed by both
      specialists and general practitioners. One serious side effect of steroid use is
      glaucoma. This complication, which can cause blindness, is often only discovered
      at the end stage. Three patients, two women aged 20 and 32 and a man aged 28
      developed glaucoma as a result of topical steroid use. It is advisable to examine
      patients annually if they have a family history of glaucoma and are using
      steroids regularly in or around the eye. Follow-up should also be considered for
      patients with a family history of glaucoma who are using systemic steroids
      regularly, and for all other patients using steroids regularly in or around the
      eye. All patients on steroids should consult their ophthalmologist speedily if
      visual symptoms occur.

PMID- 16304884
TI  - [Perioperative thromboprophylaxis--for the immobilisation period, potential
      extension beyond hospitalisation].
AB  - Antithrombotic prophylaxis of venous thromboembolism after surgery, usually by
      means of subcutaneous administration of(low-molecular-weight) heparin,
      drastically reduces the incidence of postoperative thrombosis and pulmonary
      embolism. Therefore, this intervention is advocated in various national and
      international guidelines. A questionnaire-based study in this issue shows that
      99% of surgeons in the Netherlands strictly adhere to these guidelines.
      Interestingly, the duration of thromboprophylaxis is much less clear and is
      usually restricted to the duration of hospitalisation. In view of the increasing
      number of surgical procedures in short-stay or even outpatient settings, it is
      possible that extended prophylaxis for perioperative thrombosis should be
      considered, particularly in patients with risk factors for thrombosis, such as
      the presence of malignant disease.

PMID- 16304885
TI  - [Two guidelines on community-acquired pneumonia: both an important basis for
      individual policies].
AB  - Recently, two Dutch guidelines were published regarding the management of
      patients with community-acquired pneumonia. In the Dutch Working Party on
      Antibiotic Policy (SWAB) guideline, the choice of antibiotic is based primarily
      on the severity of illness. In the Dutch Thoracic Society (NVALT) guideline,
      patients are differentiated for empiric therapy based on clinical and rapidly
      available laboratory information, placing severely-ill patients in a separate
      category. Rapid tests for detection of Legionella pneumophila antigen have a
      prominent place in both guidelines. Contrary to the NVALT guideline, the SWAB
      guideline does not value Gram staining of sputum when selecting an initial
      therapeutic choice. The antibiotics recommended in the guidelines differ.
      Clinicians should take notice of both guidelines and take the best from each to
      formulate their own personal approach to patients with community-acquired
      pneumonia.

PMID- 16304886
TI  - [Optimizing the antibiotics policy in The Netherlands. VIII. Revised SWAB
      guidelines for antimicrobial therapy in adults with community-acquired
      pneumonia].
AB  - The Dutch Working Party on Antibiotic Policy (SWAB) has revised the 1998
      guideline for community-acquired pneumonia (CAP) in light of changing resistance
      patterns for common pathogens and new developments in epidemiology, diagnostic
      testing and treatment strategies. The current guideline is applicable to both
      primary and inpatient care, and has been developed by delegates of all
      professional organisations involved in the treatment of CAP, following
      recommendations for evidence-based guideline development. Assessment of a
      patient's 'severity of illness' at presentation is considered important when
      choosing an optimal empirical antibiotic regimen for CAP. Severely-ill patients
      should be treated with antibiotics covering the most important expected
      pathogens, including Legionella. Assessment of the severity of illness may be
      facilitated by the use of validated scoring systems like the pneumonia severity
      index and the 'confusion, urea, respiratory-rate, blood-pressure, 65-years-of
      age' (CURB-65) score. Patients can also be stratified based on their location
      during treatment: in the community, a normal ward or an intensive-care unit.
      Legionella urine antigen testing is considered an important tool in the process
      of deciding on an optimal antibiotic regimen for CAP. Empirical therapy should be
      replaced with pathogen-directed therapy if the causative agent is identified.

PMID- 16304887
TI  - [Guideline 'Diagnosis and treatment of community-acquired pneumonia' from the
      Dutch Thoracic Society].
AB  - Community-acquired pneumonia (CAP) is associated with considerable morbidity and
      mortality. The incidence of CAP in the Netherlands is estimated to be 5-10 per
      1000 per year. This guideline can be used for the scientifically-based diagnosis
      and antibiotic treatment of adults with CAP. Streptococcus pneumoniae is the most
      frequent causative agent In 30-50% of patients, the aetiological pathogen cannot
      be identified. In the Netherlands, the resistance of S. pneumoniae to penicillin
      is less than 1%. In addition to patient history and physical examination, chest
      radiography is indispensable to the diagnosis of CAP. Cultures of sputum, blood,
      and, if present, pleural effusion are needed to detect the causative agent.
      Bronchoscopy can be considered if the patient's condition deteriorates during
      antibiotic therapy. Urinary antigen detection is important if signs of
      legionellosis are present; only Legionella pneumophila serotype can be identified
      with this technique. The severity of CAP and the risk factors can be measured by
      the pneumonia severity index, which may be helpful in deciding whether to
      hospitalise a patient. The choice of antibiotic therapy is based on the intention
      of providing optimal therapy, the epidemiological features ofvarious
      microorganisms in the Netherlands, and an inference of the most likely pathogen,
      based on comorbidity. Empirical antibiotic therapy should target primarily S.
      pneumoniae because of its high incidence. In both seriously ill patients and
      those suspected of having legionellosis, antibiotic therapy should also target L.
      pneumophila. Antibiotic therapy should be adjusted if the pathogen is
      subsequently identified. Parapneumonic effusion frequently occurs in cases of
      CAP. Drainage is indicated if the pleural fluid contains bacteria or yields a pH
      < 7.0. Influenza vaccination is recommended in the elderly to prevent CAP.

PMID- 16304888
TI  - [From the Cochrane Library: routine membrane sweeping ('stripping') for induction
      of labor in full-term pregnancies effective, but not always useful].
AB  - Sweeping ('stripping') of the membranes has the potential to initiate labour by
      increasing local production of prostaglandins and, thus, to reduce pregnancy
      duration or to pre-empt formal induction of labour with either oxytocin,
      prostaglandins or amniotomy. A Cochrane systematic review of 22 trials (2797
      women) comparing membrane sweeping with no treatment, with prostaglandins and
      with oxytocin revealed that stripping of the membranes was associated with
      reduced frequency of pregnancy continuing beyond 41 and 42 weeks. To avoid formal
      induction of labour in one instance, membrane sweeping must be performed in 8
      women. Discomfort during vaginal examination and other adverse effects (bleeding,
      irregular contractions) were reported more frequently by women allocated to
      sweeping. When used as a means of inducing labour, the reduction in the use of
      more formal methods of induction must be balanced against the resulting
      discomfort and other adverse effects.

PMID- 16304889
TI  - [Thromboprophylaxis in general surgical practices in the year 2004: perioperative
      use during hospitalisation, during out-patient care and following plaster cast
      immobilisation].
AB  - OBJECTIVE: To determine which thromboprophylactic modalities were used by general
      surgeons in the Netherlands; to check current clinical practice against national
      and international guidelines. DESIGN: Descriptive. METHOD: In April 2004 a
      questionnaire was sent to all 106 surgical practices in the Netherlands with
      questions regarding the use of thromboprophylaxis before, during and after
      various surgical interventions. Practice was compared with guidelines from the
      Dutch Institute for Healthcare Improvement CBO, the Dutch Surgical Association
      and the American College of Chest Physicians. RESULTS: We obtained data from 92
      (87%) surgical practices. Low molecular weight heparin was initiated before
      surgery by 92% of respondents. Risk factors such as age (72%) and prior venous
      thromboembolism (76%) played an important role in determining the
      thromboprophylactic protocol used. During hospitalisation, variations were seen
      primarily for operations performed on an out-patient basis: 61% of surgeons gave
      thromboprophylaxis in this setting. Prolonged thromboprophylaxis after hospital
      discharge was seldom administered. 54% of surgeons used prolonged
      thromboprophylaxis after surgery for hip or femur fractures. During cast
      immobilisation of the upper leg, 79% of all surgeons prescribed
      thromboprophylaxis. CONCLUSION: Current practice regarding thromboprophylaxis
      during hospitalisation conformed consistently to the guidelines. The guidelines
      were followed moderately with regard to the use of prolonged thromboprophylaxis
      following hip fractures. In the absence of clear guidelines, there were striking
      differences among surgical practices regarding thromboprophylaxis during out
      patient care and plaster cast immobilisation.

PMID- 16304890
TI  - [A man with Candida pyopneumopericarditis and cardiac tamponade in conjunction
      with gastric tube infection].
AB  - A 55-year-old man who had undergone oesophagectomy with retrosternal gastric tube
      reconstruction for oesophageal carcinoma several years before, presented with
      retrosternal pain, fever and chills. He appeared to have Candida glabratarelated
      pyopneumopericarditis and a fungal infection in the gastric tube. Because of
      cardiac tamponade, the pericardium was surgically drained. The patient was given
      antibiotics and fluconazole. He left the hospital after one month in relatively
      good condition. Two months later, he was readmitted for haematemesis. During an
      emergency surgical procedure a fistula was found between the gastric tube and the
      left atrium. For these patients is early treatment of the underlying cause
      lifesaving. Monthly check-ups in an outpatient clinic are needed due to the risk
      of constrictive pericarditis and recurrent cardiac tamponade.

PMID- 16304891
TI  - [Acute abdominal pain as the first sign of Henoch-Schonlein purpura; a hidden
      diagnosis in the absence of purpura].
AB  - 2 girls with abdominal pain, aged 7 and 9 years, were admitted and underwent
      extensive evaluation: the first girl underwent colonoscopy and the second
      appendectomy, in which a negative appendix was removed. After 6 and 14 days,
      respectively, they developed skin lesions that did not disappear on pressure,
      characteristic of Henoch-Schonlein purpura (HSP). They recovered after treatment
      with prednisone. HSP is a systemic vasculitis, which can be diagnosed by its
      characteristic purpura of the skin. Diagnosis is more difficult if the patient
      does not present with skin lesions. HSP presenting with acute abdominal pain as
      an initial symptom can give rise to unnecessary additional investigation and even
      laparotomy. Apart from the other clinical features of HSP, i.e. bloody stools,
      oligo-articular arthritis and (microscopic) haematuria, diagnosis can be made
      earlier if biopsies of the normal skin or duodenum are taken and assessed for IgA
      depositions. Treatment of the abdominal pain with corticosteroids can be
      considered.

PMID- 16304892
TI  - [Polymyalgia rheumatica and temporal arteritis].

PMID- 16304893
TI  - [Polymyalgia rheumatica and temporal arteritis].

PMID- 16304894
TI  - [Polymyalgia rheumatica and temporal arteritis].

PMID- 16304895
TI  - ['Awakening': a confusing improvement during treatment with atypical
      antipsychotic agents].

PMID- 16304896
TI  - [Bruises, loose teeth and fatigue in a patient with schizophrenia].

PMID- 16304897
TI  - [Sentinel lymph node biopsy for melanoma: prognostic value and disadvantages in
      300 patients].

PMID- 16304899
TI  - New CMS drug Web site draws ire.

PMID- 16304898
TI  - Report predicts Part D disaster if 2006 enrollment is low.

PMID- 16304900
TI  - Draft legislation would override states' privacy standards for EHRs.

PMID- 16304901
TI  - [Prostate cancer chemotherapy, myth or reality?].

PMID- 16304902
TI  - [Analysis of the scientific evidence of the combination therapy in benign
      prostatic hyperplasia].
AB  - OBJECTIVE: The analysis of the scientific evidence of the combination therapy in
      Benign Prostatic Hyperplasia (BPH). METHODS: 5 published studies about
      combination therapy in BPH were analysed following the criteria of the Evidence
      Based Medicine (EBM). Hypothesis, variables, internal validity, results
      relevance, and the external validity of every study were analysed. RESULTS:
      Symptoms changes and maximal flow rate (Qmax) improvement were evaluated in four
      studies and only one analysed the BPH progression. Inclusion and exclusion
      criteria were similar in the 5 studies. The main reasons of a poor internal
      validity in 3 studies were the short follow-up, the missing percentage, the
      absence of a placebo group and a dosage bias. External validity were decreased in
      the 5 studies by the exclusion criteria and in 3 of them because high doses of
      alpha-blocker were given to achieve a therapeutic effect. The study with the
      highest scientific evidence (MTOPS) is the only that offers confidence intervals
      and number needed to treat. CONCLUSIONS: The Qmax and the symptoms improvement
      found in all the studies has a moderate clinical relevance. MTOPS study shows
      that BPH progression has a low incidence that can be highly reduced by means of
      combination therapy.

PMID- 16304903
TI  - [Isolated intraepithelial prostatic neoplasia and positive prostate
      adenocarcinoma results at repeated biopsy. Review of our series].
AB  - OBJECTIVE: To review the incidence of isolated prostatic intraepithelial
      neoplasia (PIN) as well as the positive prostate cancer results in repeat biopsy
      in our series of transrectal biopsy of the prostate. We compare these results
      with the actual literature. MATERIALS AND METHODS: We review the 2.475
      transrectal ultrasound guided biopsies of the prostate made in our department
      from January 1992 to June 2004 looking for intraepithelial neoplasia and looking
      in particular for isolated High-grade PIN (HGPIN). We review repeat biopsies made
      at this patients and the likelihood of detecting prostate cancer in them.
      RESULTS: The diagnosis of PIN was found in 31 biopsies, 13 of them were isolated
      HGPIN what means a 0.52% incidence of the total biopsies performed in our
      department. We performed 7 repeat biopsies of the 13 cases in a period from 3
      months to 2 years after the first biopsy, and we found 3 cases of prostate cancer
      what means that 43% of isolated HGPIN with repeated biopsy showed prostate
      cancer. The mean age of the patients studied was 67 years (range 53-88). The
      median PSA value of the studied cases was 9.8 ng/ml. The Gleason score of the
      positive biopsies was always between 3 and 7. In our series, age and PSA levels
      did not have correlation with the positive results for prostate cancer in
      repeated biopsies. CONCLUSIONS: In spite of a lower number of HGPIN cases in our
      series, the positive for prostate cancer in repeated biopsy (43%) is similar to
      the incidence reported in literature so it is advisable rigorous controls and
      repeated biopsies for these patients.

PMID- 16304904
TI  - [Normothermic ischemia effects in renal microcirculation].
AB  - We report the results obtained in a experimental work designed to evaluate the
      consequences of warm ischemia in hypothermic isolated renal perfusion. We
      perfused a number of kidneys after a period of 45 min of vascular occlusion. An
      alternative group of kidneys were perfused without previous warm ischemia. Ureter
      was canulated in all the procedures and output collected during the HP.
      Creatinine was added to the perfusion solution initially in order to determine
      creatinine clearance. HP hydrodynamics was recorded on real time through a
      computerised system. According to the results, renal vascular resistance as well
      as CrCl were higher in ischemic kidneys. Both facts along with minimal
      differences in pathologic study suggest an increase in vascular tone of efferent
      postglomerular arteriole during HP. HP was an adequate technique to minimize
      histologic consequences of ischemia. Mycrovascular an biochemical changes
      produced during HP may be produced, essentially, by dynamic causes.

PMID- 16304905
TI  - [Effect of polyphenols from the Mediterranean diet on proliferation and mediators
      of in vitro invasiveness of the MB-49 murine bladder cancer cell line].
AB  - OBJECTIVE: To evaluate the effect of different polyphenols on the proliferation
      and invasive capacity of MB-49 murine bladder tumor cell lines and to identify
      the mediators involved in this process. MATERIALS AND METHODS: MB-49 murine
      bladder cancer cells were cultured in media supplemented with resveratrol, rutin,
      morin, quercetin, gallic acid and tannic acid (all of them are polyphenols
      usually present in Mediterranean diet) for periods of 24, 48 and 72 hours to
      quantify the expression of urokinase-type plasminogen activator (uPA) and its
      receptor (uPAR) in the culture medium, as well as of metalloproteinase-9 (MMP-9)
      and cell proliferation. RESULTS: All the polyphenols studied significantly
      inhibited proliferation of MB-49 cells, varying according to the time periods and
      doses used. The cells in the media supplemented with the nutrients to study did
      not show inhibition of mRNA expression of urokinase-type plasminogen activator
      (uPA) or its high affinity receptor (uPAR). It was even slightly increased in
      certain cases. However, mRNA expression of metalloproteinase-9 was strongly
      inhibited. CONCLUSIONS: The polyphenols present in our usual diet exert an effect
      on the proliferation and mediators of bladder tumor invasiveness in MB-49 cells.

PMID- 16304906
TI  - [Treatment of female stress urinary incontinence with TVT system (tension-free
      vaginal tape): complications in our first 100 cases].
AB  - INTRODUCTION: The TVT system is the most common surgical technique of female
      stress urinary incontinence, because of the simplicity. good clinical results and
      rare complications. MATERIAL AND METHODS: From april, 1999 to march. 2004, it has
      been done in our department 100 TVT systems with the revision of the result over
      the six following months. The average follow-up rate was 10.36 months (R: 1-54
      months) and looses mean the 11% of the cases. All the patients presented stress
      incontinence and their average age was 56.6 years old (30-80). The 12% of the
      cases have been previously operated of urinary incontinence. 21 patients
      presented previous surgery of pelvic floor. In the 17% of the cases, TVT systems
      was associated to another surgical technique: 15% of them was operated of
      cystocele, 1% of them had surgical correction of rectocele, 1% of them had a
      strong surgery of pelvic floor, that included TVT system, correction of pelvic
      floor and hysterectomy. RESULTS: We obtained 65% of successful cases, defined as
      objective confirmation of absence of looses from the observer and the subjective
      reference of the patient: 17% of clear improvement (clear decrease of looses from
      the patient and subjective improvement) and 7% of failure of the technique. The
      total percentage of appearance of novo post-surgery urgency is 9%. There were
      complications in the 12% of the cases: there were three cases of bladder
      perforation, two of them intra-operative and one of them deferred and associated
      to an infection of surgical wound; another three cases of residue in the
      immediate post-operative that were resolved with bladder catheterization: one
      case of acute urinary retention that was treated with bladder catheterization
      with suprapubic cistostomy: one case of chemical peritonitis corrected with a
      conservative treatment; two cases of vaginal extrusion of sling, which were
      resolved with the section of the outer sling; one patient presented a hipogastric
      hematoma resolved with conservative measures: and one patient presented pelvic
      discomfort with spontaneous resolution. CONCLUSIONS: We consider the TVT system
      as an effective surgical technique in the treatment of the female stress urinary
      incontinence. It is a simple technique with a short stay in the hospital and rare
      complications.

PMID- 16304907
TI  - [Comparison of diferents suburethral slings for the treatment of stress urinary
      incontinence].
AB  - OBJECTIVES: To compare the results of the different procedures of sling
      suburetral used in our service (TVT, Sparc, IVS, Obtape and Monarc) for the
      treatment of the female urinary incontinence. MATERIAL AND METHODS: 96 patients
      retrospective analysis affects of female urinary incontinence and subjected to
      different procedures of sling suburethral without tension. The half age: 56.1 +/-
      10.7 years. 75 patients were intervened by means of procedures retropubics (48
      TVT, 17 Sparc, 10 IVS) and 21 with obturators (10 Obtape, 11 Monarc). The half
      time of pursuit: 26.3 +/- 12.7 months (29.4 months for the methods retropubics
      and 11.7 for the obturators). The analyzed variables were: age, obesity, grade of
      previous incontinence, type of used procedure, time of pursuit, and previous
      surgical procedures. We compare the complications and the results obtained with
      the different ones technical. RESULTS: the cure percentage was of 95.7%. 7
      patients presented complications: one intestinal perforation, two bladders
      perforations, one erosion of vaginal wall, three incontinences of novo urgency.
      In 6 cases the stress incontinence persists. When analyzing the association
      between the diverse variables and the success, we appreciate that the variables
      with value presage were the age and the obesity (P < 0.05) not observing
      relationship with the technique employeed. CONCLUSIONS: The existence of multiple
      surgical approachs and a varied auxiliary materials allow each surgeon to choose
      that with the one that is more familiarized and comfortable without, seemingly,
      influence it in the results.

PMID- 16304908
TI  - [Treatment of males with post-prostatectomy stress urinary incontinence by a mesh
      anchored to the ischio-pubic bones].
AB  - We presented the results of an alternative in the treatment of the stress urinary
      incontinence of male radical postprostatectomy. Is a technique of renewed
      interest in the last years, cradle in the procedure of Stamey, consisting of
      placing an on guard suburetral polypropylene mesh, anchored by means of screws to
      the isquiopubian branches. We have applied the procedure in 4 patients and with
      stress urinary incontinence of long evolution. After an average pursuit of 12.5
      months, two patients present total continence, one has improved significantly and
      in the other the incontinence persists. There have been no postoperating
      complications nor rejection of the mesh. From these preliminary results and the
      reviewed bibliography, we thought that this technique can constitute an
      alternative to the artificial urinary sphincter, dices its clinical results, its
      facility of execution, the good tolerance and his low cost.

PMID- 16304909
TI  - [Anti-apoptotic potencial role of p38 in prostate cancer].
AB  - INTRODUCTION: TNF-alpha transduction pathway in prostate cancer seems to be
      diverted towards p38 activation. P38 may protect prostate tumoral cells from TNF
      alpha apoptosis induced. The aim of this study was study the role of p38 in vivo
      (were evaluated some p38 downstream factors), as well as in vitro (in prostatic
      tumoral cell lines, LNCaP and PC3, pre-treated with TNF-alpha). MATERIAL AND
      METHODS: Two prostatic tumoral cell lines (LNCaP and PC3) were used in in vitro
      studies. Two different experiments were made: with TNF-alpha (several
      concentrations) and p38 specific inhibitor (SB203580). The apoptotic index were
      evaluated using DAPI staining and flow cytometry. P38 activation was measured by
      Western blot analysis. 15 normal samples (NP) and 27 prostate cancer samples (PC)
      were used in in vivo study, all of them were processed for immunohistochemistry
      and Western-blot. RESULTS: In vitro, TNF-alpha induced apoptosis in LnCap when we
      increased its concentration but not in PC3. TNF-alpha stimulation led to increase
      a time-dependent p38 phosphorylation in two intermediate doses whereas in PC3 not
      changes were found. In LNCaP after its preincubation with SB203580 and TNF-alpha
      treatment showed a significative increasing of apoptosis. In vivo, all NP samples
      were found positives to p-Elk-1 and p-ATF-2 (nuclei of epithelial cells). In PC
      the expression of p-Elk-1 or p-ATF-2 increased and was located in the nucleus and
      cytoplasm of epithelial cells. CONCLUSION: Our data in vitro and in vivo suggest
      that p38 plays a very important role in prostatic tumour progression. These data
      suggest that the control activation of p38 might be a possible target to cancer
      prostate treatment.

PMID- 16304910
TI  - [Spermatic cord mass as a manifestation of systemic vasculitis: a case report and
      review of the literature].
AB  - We report a case of necrotizing granulomatous vasculitis in the spermatic cord in
      a 35-year-old man with an antecedent of brain stroke 3 years before. The clinical
      manifestation was as a painless left scrotal mass. The diagnosis was established
      by histological examination of the spermatic cord. We discuss the physical
      findings, radiological features and pathological findings, reviewing the
      literature for previous similar cases.

PMID- 16304911
TI  - [Entero-neobladder ileal fistula: two cases report].
AB  - Fistulas between the orthotopic reservoir and the gastrointestinal tract have low
      incidence (1.5-2%). Simptomatology is variable, but it's frecuent to find
      fecaluria. Among 90 new intestinal bladders we show two fistule of new bladder to
      ileo, with nest postoperatory diagnosis, using retrograde cystografy; one was
      resolved with next postoperative treatment and the other with open surgery.

PMID- 16304912
TI  - [Percutaneous treatment with BCG in multiple upper tract transitional cell
      carcinoma].
AB  - Upper tract transitional cell carcinoma is a low prevalent tumour and frequently
      associated to bladder carcinoma. The antegrade endoscopic access represents a
      safe, efficient and minimally invasive access. The association to immunotherapy
      seems effective in decreasing recurrence. We present one patient with multiple
      upper tract carcinoma treated with percutaneous surgery and BCG.

PMID- 16304913
TI  - [Giant renal oncocytoma].
AB  - Renal oncocytoma is a benign neoplasms arising from cells of the distal renal
      tubule. They acount for 3-7% of all renal tumors. most are incidental findings.
      Differential diagnosis with renal cells carcinoma is often difficult. Here we
      report a case of big renal oncocytoma as an incidental finding while performing
      an abdominal ultrasound in a patient with low abdominal pain. We also review the
      diagnostic an therapeutic approach in this kind of malignancies.

PMID- 16304914
TI  - [Renal pseudotumor secondary to acute pancreatitis. Report of one case].
AB  - We present the case of a renal pseudotumor corresponding to a esteatonecrotic
      granuloma, secondary to an enolic acute pancreatitis a few months ago. The main
      caractheristics, diagnosis and terapeuthics of the renal pseudotumors are
      discussed with the case report of a 60 year old man who presents a renal mass
      founded incidentally at a control computed tomography.

PMID- 16304915
TI  - [Treatment of Bowen's disease of the penis with imiquimod 5% cream].
AB  - We present an alternative treatment of the intraepithelial neoplasms of penis
      (Bowen's disease), the topical application of imiquimod 5% cream. It was applied
      3 times weekly for 5 weeks. Imiquimod is an imidazoquinolone immune response
      modifier that has been shown to have indirect antiviral and antitumor effects
      with few adverse effects. Imiquimod 5% cream may represent an alternative
      treatment option for Bowen's disease.

PMID- 16304916
TI  - [The use of medicinal herbs may cause serious nephrologic and urologic diseases].

PMID- 16304917
TI  - [Type IV hypersensitivity to intravesical mitomycin].

PMID- 16304918
TI  - [Natural history of upper urothelium tumors].

PMID- 16304919
TI  - [Nutcracker syndrome as cause for hematuria].

PMID- 16304920
TI  - Evidence-based practice and support surfaces: are we throwing the baby out with
      the bath water?
AB  - OBJECTIVE: This study aimed to explore aspects of the effectiveness of three
      pressure-redistributing support surfaces in routine clinical practice. METHOD: A
      non-randomised prospective cohort study was used, with skin outcomes reported for
      219 subjects at risk of pressure ulcer development. RESULTS: Few instances of new
      pressure damage were observed; these related to specific clinical issues, such as
      incontinence and inadequate use of cushions when sitting. Of the 77 subjects
      (33.3%) with pressure ulcers on recruitment into the study, most (n=70) either
      improved or remained unchanged following allocation of the support surface.
      CONCLUSION: Cohort studies do not indicate the efficacy of an intervention but
      may give an indication of effectiveness--that is, the clinical outcomes that may
      be observed in routine clinical practice.

PMID- 16304921
TI  - Treatment of diabetic foot ulcers with total contact casts: a critical review of
      the current literature.
AB  - Peripheral neuropathy is a common complication of diabetes and may lead to
      ulcers, often resulting in amputations. Total contact casts are advocated for
      healing neuropathic ulcers but there are serious reservations about its use.

PMID- 16304922
TI  - How much do we understand about the effects of ageing on healing?
AB  - Poor experimental design has contributed to a perceived association of ageing
      with delayed wound healing. Continuing research on the influence of ageing will
      allow more focused therapeutic strategies.

PMID- 16304923
TI  - Standards for laser therapy studies.

PMID- 16304924
TI  - What effect does delamination have on clinical outcomes?

PMID- 16304925
TI  - Determining pain levels in patients treated with maggot debridement therapy.
AB  - OBJECTIVE: Pain as a complication of maggot debridement therapy (MDT) has been a
      topic of some controversy. This study set out to determine pain levels in
      patients treated with MDT. METHOD: A retrospective analysis using a visual
      analogue scale (VAS) was performed: 41 patients were treated with MDT for non
      healing wounds (22 men and 19 women; average age: 67 years). Average wound
      duration was 14 months (range: two weeks to 132 months). Maggots were applied
      using the contained or the free-range techniques. Paracetamol (1 g three times
      daily) and Durogesic plaster (25 microg every three days and 50 microg the day
      before the maggot change) were given for pain relief in the outpatient clinic.
      RESULTS: Diabetic patients experienced the same amount of pain before and during
      MDT. Eight out of 20 non-diabetic patients experienced more pain during MDT than
      before; the remaining non-diabetic patients had the same amount of pain before
      and during the therapy. The difference between diabetic and non-diabetic patients
      was statistically significant (p<0.05) for all applications combined. CONCLUSION:
      In 78% of patients (29/37) pain can be adequately treated with analgesic therapy.
      However, if pain is unmanageable in the outpatient department, we believe that
      options include hospital admission, using the contained method of application or,
      in the worst case scenario, cessation of treatment. A standardised but
      individually tailored pain management protocol is mandatory.

PMID- 16304926
TI  - Using Urgotul dressing for the management of epidermolysis bullosa skin lesions.
AB  - OBJECTIVE: To evaluate the acceptability, tolerance and efficacy of Urgotul wound
      dressing in the management of epidermolysis bullosa (EB) skin lesions. METHOD:
      This was an open-label uncontrolled clinical trial involving 20 patients (I I
      adults and nine children) with EB simplex or dystrophic EB. Patients were
      selected from the register of EB patients at the investigating centre and
      included if they presented with at least one skin lesion requiring management
      with a non-adherent wound dressing. Lesions were treated with the study dressing
      for a maximum of four weeks. All dressing changes, wound parameters, pain and
      effect on quality of life were recorded. RESULTS: All patients completed the
      trial. Nineteen out of 20 wounds healed within 8.7 +/- 8.5 days. Overall, 11
      patients (55%) considered that their quality of life had improved following use
      of the dressing, which was also reported to be pain free and 'very easy' or
      'easy' to remove at most dressing changes. Nineteen out of 20 patients stated
      that they would use the study dressing to manage their lesions in future.
      CONCLUSION: This study confirmed the very good acceptability and efficacy of
      Urgotul in the treatment of skin lesions in patients with EB.

PMID- 16304927
TI  - Using topical aromatherapy for the management of fungating wounds in a palliative
      care unit.
AB  - Odour can be one of the most distressing symptoms of fungating wounds.
      Traditional dressings and creams often have little effect on odour, but the use
      of essential oils has proved effective in a palliative care setting.

PMID- 16304928
TI  - Uncertainty and precaution in environmental management.
AB  - In this paper, two different visions of the relationship between science and
      policy are contrasted with one another: the "modern" vision and the
      "precautionary" vision. Conditions which must apply in order to invoke the
      Precautionary Principle are presented, as are some of the main challenges posed
      by the principle. The following central question remains: If scientific certainty
      cannot be provided, what may then justify regulatory interventions, and what
      degree of intervention is justifiable? The notion of "quality of information" is
      explored, and it is emphasized that there can be no absolute definition of good
      or bad quality. Collective judgments of quality are only possible through
      deliberation on the characteristics of the information, and on the relevance of
      the information to the policy context. Reference to a relative criterion
      therefore seems inevitable and legal complexities are to be expected. Uncertainty
      is presented as a multidimensional concept, reaching far beyond the conventional
      statistical interpretation of the concept. Of critical importance is the
      development of methods for assessing qualitative categories of uncertainty. Model
      quality assessment should observe the following rationale: identify a model that
      is suited to the purpose, yet bears some reasonable resemblance to the "real"
      phenomena. In this context, "purpose" relates to the policy and societal contexts
      in which the assessment results are to be used. It is therefore increasingly
      agreed that judgment of the quality of assessments necessarily involves the
      participation of non-modellers and non-scientists. A challenging final question
      is: How to use uncertainty information in policy contexts? More research is
      required in order to answer this question.

PMID- 16304929
TI  - The post-normal sciences of precaution.
AB  - After centuries of optimism, science has become problematic and compromised. We
      can no longer assume that innovations are safe until proven dangerous. The
      'technocratic' approach to science, with its reductionist methodology and its
      corporate control, is no longer appropriate. We need a 'precautionary' science
      that will be 'post-normal' in character. For this, we contrast 'applied science,'
      like the 'puzzle-solving' of Kuhn's 'normal science' and the 'professional
      consultancy' like the practice of the surgeon or engineer. Rather, we have a
      situation where 'facts are uncertain, values in dispute, stakes high, and
      decisions urgent.' For high-quality decision-making, we need an 'extended peer
      community' who will bring their 'extended facts' to the dialogue. There are a
      number of initiatives that advance the post-normal programme, including the
      endeavours of Poul Harremoes and the conference on Uncertainty and Precaution in
      Environmental Management.

PMID- 16304930
TI  - Precaution, law and principles of good administration.
AB  - The precautionary principle is a legal principle concerned with the process of
      how decisions are made. In implementing and interpreting it regard must be had to
      the surrounding legal culture and in particular the principles of good
      administration in operation. Highlighting those principles emphasises that within
      a particular jurisdiction there is often very little agreement over their nature.
      Within the European Union contradictory principles are the product of:
      assumptions about risk problem-solving, the ambiguous nature of European
      administration, a concern with accountability in the face of recent food
      controversies, and the impact of international trade rules. These contradictory
      principles present a number of challenges for implementing the precautionary
      principle.

PMID- 16304931
TI  - Late lessons from early warnings: towards precaution and realism in research and
      policy.
AB  - This paper focuses on the evidentiary aspects of the precautionary principle.
      Three points are highlighted: (i) the difference between association and
      causation; (ii) how the strength of scientific evidence can be considered; and
      (iii) the reasons why regulatory regimes tend to err in the direction of false
      negatives rather than false positives. The point is made that because obtaining
      evidence of causation can take many decades of research, the precautionary
      principle can be invoked to justify action when evidence of causation is not
      available, but there is good scientific evidence of an association between
      exposures and impacts. It is argued that the appropriate level of proof is
      context dependent, as "appropriateness" is based on value judgements about the
      acceptability of the costs, about the distribution of the costs, and about the
      consequences of being wrong. A complementary approach to evaluating the strength
      of scientific evidence is to focus on the level of uncertainty. If decision
      makers are made aware of the limitations of the knowledge base, they can
      compensate by adopting measures aimed at providing early warnings of un
      anticipated effects and mitigating their impacts. The point is made that it is
      often disregarded that the Bradford Hill criteria for evaluating evidence are
      asymmetrical, in that the applicability of a criterion increases the strength of
      evidence on the presence of an effect, but the inapplicability of a criterion
      does not increase the strength of evidence on the absence of an effect. The paper
      discusses the reason why there are so many examples of regulatory "false
      negatives" as opposed to "false positives". Two main reasons are put forward: (i)
      the methodological bias within the health and environmental sciences; and (ii)
      the dominance within decision-making of short term economic and political
      interests. Sixteen features of methods and culture in the environmental and
      health sciences are presented. Of these, only three features tend to generate
      "false positives". It is concluded that although the different features of
      scientific methods and culture produce robust science, they can lead to poor
      regulatory decisions on hazard prevention.

PMID- 16304932
TI  - The precautionary principle in times of intermingled uncertainty and risk: some
      regulatory complexities.
AB  - This article explores the use of the precautionary principle in situations of
      intermingled uncertainty and risk. It analyses how the so-called uncertainty
      paradox works out by examining the Pfizer case. It reveals regulatory
      complexities that result from contradictions in precautionary thinking. In
      conclusion, a plea is made for embedment of uncertainty information, while
      stressing the need to rethink regulatory reform in the broader sense.

PMID- 16304933
TI  - Globalisation, environmental harm, and progress: the role of consensus and
      liability.
AB  - Two conditions are stated that must be fulfilled to make sure that the negative
      effects of environmental pollution and risks stemming from the spread of free
      markets and technology do not outweigh the beneficial effects of this
      development. (1) For all activities, all those who may experience the negative
      effects of the activities must have given their consent to the activities and the
      conditions under which they are performed. (2) Those who engage in activities
      without this consent must be held to unlimited and unconditional liability for
      the negative effects that the activities may cause for those who did not give
      their consent. These conditions are necessary principles for the responsible
      management of environmental harm and risks. If the conditions are not satisfied,
      then the belief that the global spread of free markets and technology is
      beneficial for all, or does not harm anyone, cannot be justified. Neither of the
      conditions is fulfilled at present. This is illustrated using examples drawn from
      international legislation regarding liability for oil transportation, energy
      production, genetically modified organisms and chemicals in the environment.
      Directions for improving existing liability legislation are identified. The
      relationship between the conditions and the precautionary principle is explained.

PMID- 16304934
TI  - Recent development in the field of international liability regimes to tackle
      environmental risks.
AB  - The polluter-pays principle requires States to take any actions that may be
      necessary to ensure that polluters bear the full environmental and social costs
      of their activities. One step to implement this principle is the development of
      regulations on environmental Civil Liability. The adoption of the UN-ECE Protocol
      on Civil Liability and Compensation for Damage caused by the Transboundary
      Effects of Industrial Accidents on Transboundary Waters (Kiev Protocol) in May
      2003 was the result of a three-year negotiation process undertaken in the
      aftermath of the Baia Mare accident in Romania. The accident caused transboundary
      water pollution in the downstream countries Hungary and Yugoslavia. Owing to the
      absence of applicable liability rules, no compensation was ever paid for the
      damage caused by the pollution. The Cartagena Protocol on Biosafety mandates the
      Parties to establish rules and procedures in the field of liability and redress.
      Here there is likely to be a longer negotiation process before an agreed regime
      on liability and redress for damage arising from the use of living modified
      organisms (LMOs) becomes available, owing to the complexity and the
      particularities of gene technology.

PMID- 16304935
TI  - The precautionary principle and international conflict over domestic regulation:
      mitigating uncertainty and improving adaptive capacity.
AB  - Disputes over invocation of precaution in the presence of uncertainty are
      building. This essay finds: (1) analysis of past WTO panel decisions and current
      EU-US regulatory conflicts suggests that appeals to scientific risk assessment
      will not resolve emerging conflicts; (2) Bayesian updating strategies, with
      commitments to modify policies as information emerges, may ameliorate conflicts
      over precaution in environmental and security affairs.

PMID- 16304936
TI  - Precautionary information-generation in science and the law.
AB  - An information-generation system should be part of precautionary approaches to
      protecting the public's health and the environment. Such a system would include
      inventories or surveys of health and the environment, monitoring of them, as well
      as scoping out or scouting for threats or other harmful things that could occur
      and providing sentinels to try to identify threats before they materialize. I,
      then, suggest some ways in which such strategies could be adopted in science and
      the law as part of a precautionary approach. Doing more to generate information
      in an anticipatory way will assist implementation of the precautionary principle
      and help remove some of the uncertainty in environmental and public health
      protections.

PMID- 16304937
TI  - Reflections on uncertainty in risk assessment and risk management by the Society
      of Environmental Toxicology and Chemistry (SETAC) precautionary principle
      workgroup.
AB  - Quantitative uncertainty assessments and the distribution of risk are under
      scrutiny and significant criticism has been made of null hypothesis testing when
      careful consideration of Type I (false positive) and II (false negative) error
      rates have not been taken into account. An alternative method, equivalence
      testing, is discussed yielding more transparency and potentially more precaution
      in the quantifiable uncertainty assessments. With thousands of chemicals needing
      regulation in the near future and low public trust in the regulatory process,
      decision models are required with transparency and learning processes to manage
      this task. Adaptive, iterative, and learning decision making tools and processes
      can help decision makers evaluate the significance of Type I or Type II errors on
      decision alternatives and can reduce the risk of committing Type III errors
      (accurate answers to the wrong questions). Simplistic cost-benefit based decision
      making tools do not incorporate the complex interconnectedness characterizing
      environmental risks, nor do they enhance learning, participation, or include
      social values and ambiguity. Hence, better decision-making tools are required,
      and MIRA is an attempt to include some of the critical aspects.

PMID- 16304938
TI  - The optimisation approach of ALARA in nuclear practice: an early application of
      the precautionary principle. Scientific uncertainty versus legal uncertainty.
AB  - The late health effects of exposure to low doses of ionising radiation are
      subject to scientific controversy: one view finds threats of high cancer
      incidence exaggerated, while the other view thinks the effects are
      underestimated. Both views have good scientific arguments in favour of them.
      Since the nuclear field, both industry and medicine have had to deal with this
      controversy for many decades. One can argue that the optimisation approach to
      keep the effective doses as low as reasonably achievable, taking economic and
      social factors into account (ALARA), is a precautionary approach. However,
      because of these stochastic effects, no scientific proof can be provided. This
      paper explores how ALARA and the Precautionary Principle are influential in the
      legal field and in particular in tort law, because liability should be a strong
      incentive for safer behaviour. This so-called "deterrence effect" of liability
      seems to evaporate in today's technical and highly complex society, in particular
      when dealing with the late health effects of low doses of ionising radiation. Two
      main issues will be dealt with in the paper: 1. How are the health risks
      attributable to "low doses" of radiation regulated in nuclear law and what
      lessons can be learned from the field of radiation protection? 2. What does ALARA
      have to inform the discussion of the Precautionary Principle and vice-versa, in
      particular, as far as legal sanctions and liability are concerned? It will be
      shown that the Precautionary Principle has not yet been sufficiently implemented
      into nuclear law.

PMID- 16304939
TI  - Uncertainty as a monster in the science-policy interface: four coping strategies.
AB  - Using the metaphor of monsters, an analysis is made of the different ways in
      which the scientific community responds to uncertainties that are hard to tame. A
      monster is understood as a phenomenon that at the same moment fits into two
      categories that were considered to be mutually excluding, such as knowledge
      versus ignorance, objective versus subjective, facts versus values, prediction
      versus speculation, science versus policy. Four styles of coping with monsters in
      the science-policy interface can be distinguished with different degrees of
      tolerance towards the abnormal: monster-exorcism, monster-adaptation, monster
      embracement, and monster-assimilation. Each of these responses can be observed in
      the learning process over the past decades and current practices of coping with
      uncertainties in the science policy interface on complex environmental problems.
      We might see this ongoing learning process of the scientific community of coping
      with complex systems as a dialectic process where one strategy tends to dominate
      the field until its limitations and shortcomings are recognized, followed by a
      rise of one of the other strategies. We now seem to find ourselves in a phase
      with growing focus on monster assimilation placing uncertainty at the heart of
      the science-policy and science-society interfaces.

PMID- 16304940
TI  - Management of environmental uncertainty in maintenance dredging of polluted
      harbours in Norway.
AB  - High levels of toxic chemicals such as tributyltin (TBT) have been found in the
      bottom sediments of many Norwegian harbours. Norwegian environmental authorities
      consider maintenance dredging of such harbours to be potentially harmful to the
      environment due to the suspension and spread of polluted sediments during the
      dredging operation. Accordingly, permission to dredge may be denied, or special
      environmental measures may be required on a case-to-case basis. In this paper, we
      describe the prevailing uncertainty in the assessment of the environmental
      effects. Employing Jerome Ravetz' distinction between practical and technical
      problems in the analysis of a case study from Northern Norway, we show the
      disadvantages with an exclusive focus on technical solutions. Finally, we discuss
      informal and simple means to strengthen the presence of the practical problem in
      the decision process and thereby improve the management of uncertainty.

PMID- 16304941
TI  - Stretched peer-review on unexpected results (GMOs).
AB  - Science is the basis for governance of risk from genetically modified organisms
      (GMO), and it is also a primary source of legitimacy for policy decision.
      However, recently the publication of unexpected results has caused controversies
      and challenged the way in which science should be performed, be published in
      scientific journals, and how preliminary results should be communicated. These
      studies have subsequently, after being accepted for publication within the peer
      review process of leading scientific journals, been thoroughly re-examined by
      many actors active within the GMO debate and thereby drawn extensive media
      coverage. The publicized charges that the research involved does not constitute
      significant evidence or represent bad science have in fact deflected attention
      away from the important questions related to ecological and health risks raised
      by the research. In this paper, I will argue that unexpected findings may
      represent "early warnings." Although early warnings may not represent reality,
      such reports are necessary to inform other scientists and regulators, and should
      be followed up by further research to reveal the validity of the warnings.
      Furthermore, science that embraces robust, participatory and transparent
      approaches will be imperative in the future to reduce the present controversy
      surrounding GMO use and release.

PMID- 16304942
TI  - Precaution and Participatory Integrated Assessment of GM crops in Spain.
AB  - Qualitative Participatory Integrated Assessment (PIA) has been carried out to
      unveil the different accounts and uses of the precautionary principle and of the
      precautionary approach in the management of Bt commercial crops in Spain. In
      particular, two main interpretations have been identified: a case by case
      precaution (or caution) and a systemic precaution. Three scenarios on the
      plausible causes and consequences of commercial GM crops policy futures and the
      role of the precautionary principle and of precaution in them were also
      developed. Further research found that these scenarios could be linked to two
      broader worldviews about different plausible societies, models of agriculture,
      and of the role of ethics in the management of science and technology. It is
      argued that such worldviews, which go beyond the bounded rationality of
      scientific expertise on commercial GM crops, are used by policy makers in Spain,
      rather than or in conjunction with expert assessments, to make complex decisions
      in situations of large uncertainties and high stakes.

PMID- 16304943
TI  - Integrated management of natural resources: dealing with ambiguous issues,
      multiple actors and diverging frames.
AB  - Uncertainty is an increasingly important concern when trying to manage complex
      systems of interrelated natural resources. Scientific knowledge or necessary
      information may be lacking or incomplete. Additionally, the multiple and
      interdependent users of those resources may diverge in defining what really is at
      stake. When they frame issues in very different ways, ambiguity results, i.e.,
      the existence of two or more equally plausible interpretation possibilities.
      Environmental management in these conditions implies a shift in attention from
      solving clearly delineated problems to continuous negotiating and tuning between
      different actors and expertise domains. This requires dealing with the frame
      differences in a reciprocal way by mutually acknowledging frames and connecting
      them. Some or all parties will have to revise, enlarge or reframe the way they
      relate to the issues and to each other, in order to support mutual understanding
      and common action. The contribution of experts does not consist then in providing
      total predictability nor in predefining issues and solutions, but in supporting a
      joint learning and negotiation process among different actors and in feeding this
      process with relevant information. Behavioural simulations may play an important
      function to stimulate multi-actor learning and negotiation processes.

PMID- 16304944
TI  - A guidance for assessing and communicating uncertainties.
AB  - In the daily practice of science for policy, as experienced by governmental
      agencies which inform the policy and the public on the state and outlook of the
      environment, there is a pressing need for guidance in assessing and communicating
      uncertainties. This need extends beyond the quantitative assessment of
      uncertainties in model results, and focuses on the entire process of
      environmental assessment, running from problem framing towards reporting the
      results of the study. Using the Netherlands Environmental Assessment Agency
      (RIVM/MNP) as a case, the development, structure and content of such a guidance
      system is highlighted. Conditions for a successful implementation of the guidance
      system are discussed, and some prospects for future work are outlined.

PMID- 16304945
TI  - Experiences with the NUSAP system for multidimensional uncertainty assessment.
AB  - This paper discusses recent experiences with the NUSAP system for
      multidimensional uncertainty assessment, based on case studies that vary in
      complexity. We show that the NUSAP method, and especially the pedigree analysis
      part of it, is useful to assess not only parameter uncertainty but also to
      systematically reflect upon (model) assumptions and problem frames. A diagnostic
      diagram can be used to synthesize results of quantitative and qualitative
      analysis. It provides an analytic tool to prioritize uncertainties according to
      quantitative and qualitative insights in the limitations of available knowledge.
      We further show that extension of the pedigree scheme to include societal
      dimensions of uncertainty, such as problem framing and value-laden assumptions,
      further promotes reflexivity and collective learning. When used in a deliberative
      setting, NUSAP pedigree assessment has the potential to foster a deeper social
      debate and a negotiated management of complex environmental problems.

PMID- 16304946
TI  - Using the W&H integrated uncertainty analysis framework with non-initiated
      experts.
AB  - The W&H (Walker and Harremoes) integrated uncertainty analysis framework was put
      forward with the aim of providing a conceptual basis for the systematic treatment
      of uncertainty in model-based decision support activities such as policy
      analysis, integrated assessment and risk assessment. It provides a heuristic tool
      that can be applied in decision support exercises to classify and report the
      various dimensions of uncertainty. The intention is to stimulate better
      communication among analysts as well as between them and policymakers and
      stakeholders. The framework successfully articulates diverse scholarly
      understandings of 'uncertainty', 'ignorance', and 'quality' in science for
      policy, Nevertheless, experience with the W&H framework has revealed that many of
      the concepts put forward are relatively unfamiliar--and perhaps somewhat
      controversial--to experts practising decision support. Thus, efforts are required
      to communicate the W&H framework to experts in such a way that their knowledge of
      uncertainty is elicited adequately, without them being overly intimidated or
      confused by the novelty of the concepts presented to them. After introducing the
      W&H conceptual framework, this paper presents the methodology that was used in
      applying the W&H framework in expert elicitations on uncertainty in the risk
      assessment of genetically modified crops. Experiences with the use of this
      methodology are discussed and recommendations for further improvement are given.

PMID- 16304947
TI  - An integrated methodology for recording uncertainties about environmental data.
AB  - Understanding the limitations of environmental data is essential both for
      managing environmental systems effectively and for encouraging the responsible
      use of scientific research when knowledge is limited and priorities are varied.
      Using a combination of quantitative and qualitative techniques for assessing
      probabilities, and acknowledging the importance of scenarios where probabilities
      cannot be determined, an integrated methodology is presented for handling
      uncertainties about environmental data. The methodology is based on a fourfold
      distinction between the empirical quality of data (and the ancillary information,
      such as 'scale', required to interpret this), the sources of uncertainty in data,
      the 'fitness for use' of the data, and the quality or 'goodness' of an
      uncertainty model.

PMID- 16304948
TI  - Sources of uncertainty in economic analysis of the Water Framework Directive.
AB  - The Water Framework Directive (WFD) imposes a new approach to water resource
      management in the EU states. Uncertainty surrounding its implementation, however,
      could badly affect the achievement of the objectives set by the Directive.
      Although not directly linked to a set of techniques to deal with it, the WFD and
      accompanying guidance documents mention uncertainty as a relevant factor in
      implementing the WFD and especially in the context of economic analysis of water
      uses. In this paper we review several sources of uncertainty surrounding economic
      analysis focusing on uncertainty related to socioeconomic descriptors of river
      basins and water uses and uncertainty surrounding the selection of measures (WFD
      article 11). While a number of sources of uncertainty in socioeconomic
      descriptors of river basins and water uses are discussed, we argue that the
      transformation of this information into hydrological spatial units may turn out
      to be a real challenge for uncertainty assessment. For the choice of the most
      appropriate measures, we distinguish between uncertainty being 'internalised' in
      decisions (by using stochastic decision methods) and uncertainty stemming from
      the application of these methods.

PMID- 16304949
TI  - On the concept of model structural error.
AB  - A consideration of model structural error leads to some particularly interesting
      tensions in the model calibration/conditioning process. In applying models we can
      usually only assess the total error on some output variable for which we have
      observations. This total error may arise due to input and boundary condition
      errors, model structural errors and error on the output observation itself (not
      only measurement error but also as a result of differences in meaning between
      what is modelled and what is measured). Statistical approaches to model
      uncertainty generally assume that the errors can be treated as an additive term
      on the (possibly transformed) model output. This allows for compensation of all
      the sources of error, as if the model predictions are correct and the total error
      can be treated as "measurement error." Model structural error is not easily
      evaluated within this framework. An alternative approach to put more emphasis on
      model evaluation and rejection is suggested. It is recognised that model success
      or failure within this framework will depend heavily on an assessment of both
      input data errors (the "perfect" model will not produce acceptable results if
      driven with poor input data) and effective observation error (including a
      consideration of the meaning of observed variables relative to those predicted by
      a model).

PMID- 16304950
TI  - Model uncertainty--parameter uncertainty versus conceptual models.
AB  - Uncertainties in model structures have been recognised often to be the main
      source of uncertainty in predictive model simulations. Despite this knowledge,
      uncertainty studies are traditionally limited to a single deterministic model and
      the uncertainty addressed by a parameter uncertainty study. The extent to which a
      parameter uncertainty study may encompass model structure errors in a groundwater
      model is studied in a case study. Three groundwater models were constructed on
      the basis of three different hydrogeological interpretations. Each of the models
      was calibrated inversely against groundwater heads and streamflows. A parameter
      uncertainty analysis was carried out for each of the three conceptual models by
      Monte Carlo simulations. A comparison of the predictive uncertainties for the
      three conceptual models showed large differences between the uncertainty
      intervals. Most discrepancies were observed for data types not used in the model
      calibration. Thus uncertainties in the conceptual models become of increasing
      importance when predictive simulations consider data types that are extrapolates
      from the data types used for calibration.

PMID- 16304951
TI  - Impact of morphological parameters on water quality variables of a regulated
      lowland river.
AB  - An efficient method to investigate which morphological changes have greatest
      impact on the water quality is to carry out a computer modelling exercise. In
      this study, three models, a hydrodynamic (DYNHYD), a eutrophication model
      (EUTRO), and a sediment and micro-pollutant transport model (TOXI), were coupled
      together in the High Level Architecture (HLA) platform. DYNHYD dynamically
      simulates the propagation of a wave through a river reach one-dimensionally by
      solving the full dynamic wave equation. Important parameters that describe the
      river morphology are the roughness coefficient and the weir discharge
      coefficient. EUTRO simulates the phytoplankton-nutrient dynamics in water bodies
      with variables and parameters that regulate the process in this cycle. Examples
      of some of the more important parameters are the oxygen reaeration, phytoplankton
      growth or nitrification rates. TOXI was implemented to simulate the transport of
      sediments and heavy metals in which the most important transformation process of
      the metals was sorption. It is the aim of this study to see the effect that
      hydrodynamic parameters such as weir discharge and roughness coefficients have on
      water quality constituents, such as chlorophyll-a, dissolved oxygen and levels of
      ammonium and dissolved zinc.

PMID- 16304952
TI  - The case of Lake Balaton: how can we exercise precaution?
AB  - Balaton is the largest shallow lake in Central Europe and the most important
      recreational area in Hungary. Water balance of the lake is positive, while
      natural water level fluctuation has been significant. In 2000, an extreme drought
      period started. Until 2003, water level dropped about 70 cm (about 20% of the
      average depth). Public concern grew and the idea of water transfer from the Raba
      River was raised. To examine possible impacts a comprehensive study was prepared.
      The main question was whether water transfer was really needed and what criterion
      should be applied. For developing the methodology, three pillars were used: the
      potential climate change, the precautionary principle and the EU Water Framework
      Directive. The study covered impacts of the planned water transfer on the Raba
      Balaton system in terms of changes of the water regime, water demands and
      quality, nutrient loads and ecosystems. The Thomas-Fiering ARMA model was used
      for characterizing monthly change of the natural water resources of the lake. A
      Monte Carlo generator was developed to analyze the occurrence of extreme events,
      uncertainties, possible climate change impacts and water level control
      strategies.

PMID- 16304953
TI  - Carbon sequestration, the precautionary approach and the responsibility of
      scientists.
AB  - This paper reviews problems connected to the use of the deep-sea and sub-sea
      geological formations for carbon sequestration. We will focus on the risks and
      dangers involved in using this kind of large-scale engineering approach, which is
      not yet fully tested, to combat global warming. We will not provide a complete
      discussion on the technologies involved, but concentrate on a few principal
      questions, such as the responsibility of environmental scientists involved in
      this research. We will also discuss carbon sequestration in relation to the
      precautionary approach. We argue that there may be a place for large-scale
      engineering attempts, but this should be the last rather than the first option.

PMID- 16304954
TI  - Uncertainty, imprecision, and the precautionary principle in climate change
      assessment.
AB  - Statistical decision theory can provide useful support for climate change
      decisions made under conditions of uncertainty. However, the probability
      distributions used to calculate expected costs in decision theory are themselves
      subject to uncertainty, disagreement, or ambiguity in their specification. This
      imprecision can be described using sets of probability measures, from which upper
      and lower bounds on expectations can be calculated. However, many
      representations, or classes, of probability measures are possible. We describe
      six of the more useful classes and demonstrate how each may be used to represent
      climate change uncertainties. When expected costs are specified by bounds, rather
      than precise values, the conventional decision criterion of minimum expected cost
      is insufficient to reach a unique decision. Alternative criteria are required,
      and the criterion of minimum upper expected cost may be desirable because it is
      consistent with the precautionary principle. Using simple climate and economics
      models as an example, we determine the carbon dioxide emissions levels that have
      minimum upper expected cost for each of the selected classes. There can be wide
      differences in these emissions levels and their associated costs, emphasizing the
      need for care when selecting an appropriate class.

PMID- 16304955
TI  - Resources and uncertainties in evaluation of chemicals: basic methodological
      developments.
AB  - Conscious handling of uncertainty is critical in the assessment of chemicals,
      where the demand of knowledge is high compared to the available amount of
      resources. Consequently weighing between the use of resources and the acceptance
      of uncertainty has to be a transparent process and this sets up a challenge in
      relation to the application of mathematical methods. The maximum entropy
      principle is a useful paradigm for setting up prior information that is as non
      informative as possible. It is shown how the use of partial ordering for deriving
      ranking results can be considered as a maximum entropy strategy in relation to
      the model structure uncertainty. In this way it seems possible to solve central
      parts of the problem of resource optimising risk assessment by combining the
      precautionary principle and screening before more detailed risk assessment is
      undertaken. The non-parametric approach of partial order technique further
      appears to be more transparent than most other ranking methodologies for complex
      systems. Because in the partial order techniques, no more or less known
      uncertainty will be hidden in the application of specific weighting factors and
      functional relationships among the criteria.

PMID- 16304956
TI  - [Under-registry of maternal death in Merida, Yucatan, Mexico (1997-2001)].
AB  - OBJECTIVE: To analyze the subregistry of maternal deaths in Merida, Yucatan,
      Mexico. MATERIAL AND METHODS: The subregistry was studied using descriptive,
      cross-sectional and retrospective approaches. Acts and death certificates of
      women aged 9 to 50 years that passed away in five years (1997-2001) were
      reviewed. Additionally, an interview with their relatives was conducted plus a
      revision of clinical files and reports of autopsies. The maternal deaths were
      classified according to the criteria of the International Statistical
      Classification of Diseases and Related Health Problems (tenth revision). Maternal
      deaths found during the period of study were compared with those reported by the
      official organism in order to detect their subregistry. RESULTS: 21 cases of
      maternal deaths were found during the study period, from them 16 were notified
      officially. The subregistry of maternal deaths was 24% in the five analyzed
      years. CONCLUSIONS: Maternal mortality continues to be a public health problem in
      urban areas, like the city of Merida. It is necessary to design strategies to
      avoid the subregistry and allow the reduction of maternal deaths.

PMID- 16304957
TI  - [Acceptability of a test for antibodies against HIV in a group of pregnant women
      in Yucatan, Mexico].
AB  - OBJECTIVE: To evaluate the acceptability of a test for antibodies against HIV (Ab
      HIV) in a group of pregnant women in Yucatan, Mexico. PATIENTS AND METHODS: A
      clinical and epidemiological study was carried out on 310 pregnant women at
      different health centers in Yucatan Mexico, from January 2000 to March 2001. A
      questionnaire was applied to determine information in relation to HIV infection
      and acceptability of the test. Prior counselling was given to all those who
      accepted being tested. RESULTS: The median age was 24 (range 14 to 42). A 64.5%
      had a basic education, 91.6% were homemakers; 38% of the sexual partners worked
      away from home; 15% said they had more than one sexual partner; 31% had
      leukorrhea at the time of testing and 69% at some time in the past. Ninety
      percent of the women accepted being tested for HIV and all of them showed
      negative results. CONCLUSION: The acceptability of the test was similar to that
      reported in the international literature. The cost benefits of such a test must
      be considered, but always within the values of prevailing normative and respect
      of human rights of women. Despite zero prevalence, we found factors favourable
      for HIV infection.

PMID- 16304958
TI  - [Epidemiological analysis of infertility in a Mexican population].
AB  - BACKGROUND: Infertility is defined as the failure to conceive after a year of
      sexual life without a method of birth control. Most studies indicate that 15% of
      all couples will experience primary or secondary infertility in some moment of
      their reproductive life. OBJECTIVE: To gain knowledge of general characteristics
      from patients with infertility in our environment (social, clinical, diagnostic
      and therapeutic) that attended the Reproductive Biology Department of Hospital
      Juarez de Mexico. PATIENTS AND METHODS: A descriptive, observational,
      situational, and retrospective indagatory study was performed on 116 infertile
      patients, seen in the outpatient clinic, from January through December 1999. All
      had entered our protocol of infertility and selected treatment. RESULTS: The
      altered ovarian endocrine factor was the most frequent (82.7%), followed by
      cervical factor (80%), masculine factor (38%) and tuboperitoneal factor (29%). In
      most cases the cause was multifactorial. The percentage of successful pregnancies
      (31.88%) was similar to that reported in the literature. CONCLUSIONS: The most
      common factors that influence infertility resembled those exhibited by
      specialized clinics of affluent countries with similar pregnancy rates.

PMID- 16304959
TI  - [Quantification of perinatal risk in Mexican adolescents: consequences of
      maternal low weight].
AB  - OBJECTIVE: To determine whether a pregnant adolescent whose weight-for-age is
      less than 90% is on the risk of delivering a baby who is small for gestational
      age. PATIENTS AND METHOD: Six hundred and one adolescents aged 12-16 years, at 40
      weeks of gestation were included. Body weight was measured at baseline with
      Mexican reference tables. Low maternal weight was considered less than 90%. Rate
      of small for gestational age at birth was determined for each group. Comparisons
      were made using chi2 and relative risks were estimated. RESULTS: The rate of
      small for gestational age among adolescents with low body weight was 16.1%
      (30/186), it differed significantly (36/415) from the others (8.7%). Relative
      risk for small for gestational age babies among adolescents with low body weight
      was 1.9 (95% CI, 1.2 - 2.9). An exploratory analysis suggests that this effect
      depends on gestational age. CONCLUSIONS: If body weight of a pregnant adolescent
      is to be evaluated in the absence of a previous record, tables by Arroyo can be
      used as reference; if body weight is less than 90%, then you have an indicator of
      perinatal risk.

PMID- 16304960
TI  - [Recent concepts in gestational diabetes' etiopathogenesis].
AB  - Changes in insulin action cause maternal adaptation to fetal nutrient demand.
      Insulin resistance generates a greater production of insulin to compensate this
      resistance; however, there could be failure of pancreatic beta-cells to
      compensate by adequate insulin secretion. Factors linked to the development of
      gestational diabetes are: increased concentrations of placental growth hormone;
      peptides produced by adipose tissue, which show predictive value for the
      development of insulin resistance; adverse effects of intrauterine food
      restriction; autoimmunity induced by the consumption of some nutrients in early
      neonatal life; viral infections in children, which could damage pancreatic islets
      and become incapable of responding to metabolic overload such as pregnancy.

PMID- 16304961
TI  - [Antagonists: from physiology to assisted reproduction].
AB  - The objective of this article was to make a detailed review of the biological and
      clinical effects of a relatively new medication: the gonadotropin-releasing
      hormone antagonists. The GnRH antagonists have had an increasingly consumption
      since their release in the last three years. This review will discuss current
      strategies and potential applications for the GnRH antagonists. According to
      this, results on assisted reproduction procedures will be analyzed.

PMID- 16304962
TI  - [Phyllodes tumor and pregnancy. A report of a case].
AB  - Phyllodes tumor is a rare breast fibroepithelial neoplasm of the breast,
      predominant in females (0.3 to 0.5%). Few cases have been described in males.
      Phyllodes tumor during pregnancy grows fast and its size is relatively big. These
      tumors can be classified as benign, malignant or neighboring. A 32-year-old
      patient at 23.4 week of gestation was admitted in the National Institute of
      Perinatology with a rapidly growing mass in the right breast; diagnosis confirmed
      by ultrasound study reporting echoic images on right breast, 10 x 10 cm the
      greatest and 3x3 cm the smallest. A simple mastectomy was performed at the 26.6
      week of gestation on the right breast. A possible phyllodes tumour in the right
      breast was observed during surgery, weight 9.6 pounds, with partial infiltration
      to major pectoral muscle. Pathology reported a benign phyllodes tumor in the
      right breast, with surgical borders free of tumor. Phyllodes tumor is rare and
      can occur during pregnancy. It is unknown if the tumor is hormone-dependent. The
      growth of a tumor on a subsequent pregnancy is not necessarily associated with
      recurrency or with a new disorder on the patient, who has had a complete
      excision.

PMID- 16304963
TI  - [Selections of World Medical Press. 1949].

PMID- 16304964
TI  - [The International Academy of Perinatal Medicine selected Dr. Samuel Krachmer as
      a member].

PMID- 16304965
TI  - [Overweight and obesity among health-professional women].
AB  - OBJECTIVE: To determine the prevalence of overweight and obesity among women
      health service workers. PATIENTS AND METHODS: A cross-sectional study was
      conducted during the 2002-2003 period. We included 487 workers of the Instituto
      Mexicano del Seguro Social in Colima, Mexico. We carried out a clinical
      measurement of weight and height. The indicator of overweight and obesity was
      obtained from the body mass index, that is, a person's weight in kilograms
      divided by height in meters squared. The used criteria were similar to the ones
      established by the WHO: well-nourished (BMI from 18.5 to 24.9), overweight (BMI
      from 25.0 to 29.9), and obesity (BMI = 30). The obtained data were captured in a
      computer terminal and processed by means of an automated model. We calculated the
      frequencies distribution and the prevalence. RESULTS: Of the 487 women, 121 (25%)
      had an appropriate weight, 210 (43%) showed overweight, and 156 (32%) had
      obesity. CONCLUSIONS: The overweight and obesity prevalence among the women
      health service workers was of 75%.

PMID- 16304966
TI  - [Perinatal implications of pregnancy in adolescent women].
AB  - OBJECTIVE: To establish if there are differences on obstetric and perinatal
      outcomes between adolescents who are younger than 16 with young adults aging 20
      to 24 years old. PATIENTS AND METHOD: A double-cohort prospective and comparative
      study in 328 Mexican pregnant women. Cohort I included 153 pregnant adolescents
      younger than 16 years old and cohort II included 175 young adults aging 20 to 24
      years old. Inclusion criteria for both groups were: healthy, singleton,
      primigravidas, with 4 or more antenatal care visits and delivery at institution.
      STATISTICAL ANALYSIS: descriptive, t-test, chi-squared and Fisher's exact test.
      RESULTS: Cohort I: Mean age, 15 years old. Mean gestational age on first visit,
      22.35 +/- 6.75 weeks. Morbidity was due mainly by vaginitis and vaginosis (p =
      0.0001), urinary tract infection (p = 0.110) and anemia (p = 0.0001). Maternal
      weight on first visit was 54.11 +/- 9.11 (p = 0.001). In cohort II mean maternal
      age was 22 years old with a mean gestational age on first visit of 19.58 +/- 7.94
      weeks. Main morbidity was: urinary tract infections, vaginitis-vaginosis and
      preeclampsia (p = 0.191). Mean maternal weight on first visit was 60.37 +/- 9.99.
      Gestational age on delivery and birth weight were not statistically different
      between newborns in each group. CONCLUSIONS: Pregnancy in adolescents should be
      considered of risk; nevertheless, adequacy in antenatal care provides good
      obstetric and perinatal outcomes.

PMID- 16304967
TI  - [Usefulness of fetal biophysical profile in preterm rupture of membranes with
      treatment].
AB  - OBJECTIVE: To evaluate the usefulness of the fetal biophysical profile as a
      predictor of early neonatal infection in patients with preterm rupture of
      membranes in conservative management. PATIENTS AND METHODS: This is a validation
      study of a diagnostic test. Between November, 2001 and August, 2003, 75 patients
      with 27 to 33 weeks of gestation and preterm rupture of membranes in conservative
      management were studied. Daily, a fetal biophysical profile was applied to them.
      Statistical analysis was done with chi square test and with a 2 x 2 contingency
      table that compared the biophysical score of + 8 and < or = 6 versus the presence
      or absence of early neonatal infection. RESULTS: The biophysical score < or = 6
      was associated with early neonatal infection (p < 0.05), with sensitivity,
      specificity, positive and negative predictive values of 80, 85, 64 and 85%,
      respectively (OR 9.73, 95% CI: 2.88-34.63; p = 0.0000164). CONCLUSIONS: The
      biophysical score < or = 6 was significantly associated with early neonatal
      infection.

PMID- 16304969
TI  - [New biochemical and molecular aspects of estrogen's action].
AB  - Estrogens have several biologic actions. The specific nuclear actions of
      estrogens are determined by the hormone structure, the isoform subtype of the
      involved estrogen receptor, the characteristics of the target gene promoter, and
      the balance between coactivator and corepressor proteins that modulate the final
      transcriptional response of the complex between estrogens and its receptors. In
      this review we focus on the new biochemical and molecular aspects of the
      estrogens action.

PMID- 16304968
TI  - [Selective estrogen receptors modulators (SERMs): biochemistry, pharmacology, and
      clinical use in gynecology].
AB  - The selective strogen receptors modulators (SERMs) were initially developed as
      antistrogens for the treatment of breast cancer, but their unusual properties
      have led to their use in the treatment and prevention of other diseases as well.
      SERMs bind the strogen receptor (ER) and modulated ER-mediated gene
      transcription. Tamoxifen is an effective treatment for hormone responsive breast
      cancer and can prevent breast cancer in high-risk women. Raloxifene was approved
      for the prevention and treatment of osteoporosis in postmenopausal women, also
      appears to prevent breast cancer. Other SERMs are in development, with the goal
      of improving efficacy and reducing toxicity.

PMID- 16304970
TI  - [Socio-demographic impact of 15 years of family planning].
AB  - Familiar planning is an important branch of the preventive medicine that can have
      a great impact on the health of the humanity. The present study is an evaluation
      by a cross section of the effects obtained by the program of familiar planning
      during a period of 15 years in the Aguascalientes Delegation of the Mexican
      Institute of the Social Security, establishing therefore a diagnosis and
      identifying elements that can contribute in the suitable planning of strategies
      to improve the quality of the attention and to respond to social and health
      necessities of the population.

PMID- 16304971
TI  - [Prenatal ultrasound diagnosis of adrenal neuroblastoma].
AB  - Neuroblastoma is the most frequent solid malignant tumor in the neonatal period;
      however, its diagnosis is very difficult in the prenatal one. This kind of tumor
      has a high morbidity and mortality rate due to the metastatic risk. Its prognosis
      depends on the affected area, on the extension of the tumor, and on the
      associated abnormalities. The antenatal ultrasound diagnosis is possible by
      finding a mixed mass in the adrenal gland. We report a case of a bilateral
      adrenal neuroblastoma diagnosed by antenatal ultrasonography at the 29th week of
      gestation. We describe the principal findings and show the contribution of the
      tridimensional ultrasound on the relationship of the tumor with the nearby
      structures.

PMID- 16304972
TI  - [Spontaneous uterine perforation secondary to pyometra: a report of three cases].
AB  - We performed a retrospective observational review-based study of the medical
      records of consecutive women with diagnosis of spontaneous uterine perforation,
      between 1995 and 2003. During this period 3 patients with an average age of 76.2
      years and with acute abdominal pain attended to the emergency department.
      Physical examination revealed signs of peritoneal irritation, as a result
      emergency laparotomy was performed, where uterine perforation was not found in
      the preoperative diagnosis. All patients had purulent fluid in the abdominal
      cavity and uterine perforation. A total abdominal hysterectomy with bilateral
      salpingooophorectomy was carried out under the diagnosis of generalized
      peritonitis caused by spontaneous perforation of pyometra. They also required
      cavity lavage, drainages placement, and antibiotics. Histological examination
      revealed uterine perforation and pyometra without evidence of malignancy.
      Prognosis was good and they were discharged on postoperative day 8.5 without
      complications. Spontaneous uterine perforation, secondary to pyometra, should be
      considered in the differential diagnosis of acute abdomen in postmenopausal
      patients, still without gynecological signs.

PMID- 16304973
TI  - [The epidemics has reached us].

PMID- 16304974
TI  - [Surgical indication in cervix cancer. Which cervix blastomas should we operate?
      1950].

PMID- 16304975
TI  - Sixth meeting of the Steering Committee on Immunization Safety.

PMID- 16304976
TI  - Performance of acute flaccid paralysis (AFP) surveillance and incidence of
      poliomyelitis, 2004-2005 (data received in WHO Headquarters as of 25 October
      2005).

PMID- 16304977
TI  - Endoscopic fourth ventricular aqueductoplasty.

PMID- 16304978
TI  - Transtentorial approach.

PMID- 16304979
TI  - Endoscopic aqueductoplasty through a tailored craniocervical approach.
AB  - OBJECT: Neuroendoscopy has an essential role in the management of occlusive
      hydrocephalus due to a membranous obstruction of the sylvian aqueduct. Well-known
      endoscopic methods include endoscopic third ventriculostomy (ETV) and endoscopic
      aqueductoplasty through a frontal burr hole. Building on their experience in the
      endoscopic management of hydrocephalus, the authors realized that not all of
      their patients with aqueductal obstruction were eligible for the aforementioned
      lines of treatment. Certain anatomical situations made it impossible to perform
      ETV or endoscopic aqueductoplasty through a frontal burr hole. Long-term
      complications of the shunt system led the authors to seek an alternative form of
      treatment for these patients. In this study, they present a new endoscopic
      approach to performing aqueductoplasty through the fourth ventricle. METHODS:
      Endoscopic aqueductoplasty was performed in five patients by using a tailored
      craniocervical approach. In all patients a caudally located membranous
      obstruction of the sylvian aqueduct was present, and the authors were able to
      relieve the membranous obstruction in all patients without complications. All
      patients experienced improvement, which was demonstrated clinically and on
      imaging studies. CONCLUSIONS: Caudal endoscopic aqueductoplasty is a safe and
      effective method of treatment in the management of a caudally located membranous
      obstruction of the sylvian aqueduct. This should be considered as an alternative
      endoscopic method when other endoscopic solutions are not suitable.

PMID- 16304980
TI  - Posterior subtemporal transtentorial approach to intraparenchymal lesions of the
      anteromedial region of the superior cerebellum.
AB  - OBJECT: To overcome the limitations associated with surgical approaches that have
      been described for accessing intraparenchymal lesions of the anteromedial region
      of the superior cerebellum, the authors used a posterior subtemporal
      transtentorial approach to remove tumors in this region. In this paper they
      describe the surgical technique that they used as well as the operative findings
      and clinical outcomes observed in patients who underwent resection of tumors in
      the anteromedial superior cerebellum. METHODS: The consecutive patients with
      anteromedial superior cerebellar tumors who underwent resection performed using
      the posterior subtemporal transtentorial approach at the National Institutes of
      Health were included in this study. Clinical, neuroimaging, and operative results
      were analyzed. Three patients (two men and one woman) with anteromedial superior
      cerebellar tumors (two hemangioblastomas and one pilocytic astrocytoma) underwent
      resection via this approach. All the tumors were larger than 3 cm in diameter
      (range 3.1-3.5 cm). This approach provided excellent surgical access and
      permitted complete tumor resection in each case. The patients remained
      neurologically unchanged compared with preoperative baseline findings at the last
      follow-up examination (conducted at 4, 18, and 42 months postoperatively). One
      patient displayed a mild transient confusion immediately after surgery, but it
      resolved within 6 days. CONCLUSIONS: The posterior subtemporal transtentorial
      approach provides excellent access to the anteromedial superior cerebellar
      region. This approach permits resection of large lesions in this location, while
      avoiding many of the limitations associated with other approaches to this site.

PMID- 16304981
TI  - Surgery for primary brain tumors at United States academic training centers:
      results from the Residency Review Committee for neurological surgery.
AB  - OBJECT: Surgery for primary brain tumors has been an important index of the
      quality of neurosurgical training programs in the US. The scope of such cases and
      the proportion of surgeries performed transsphenoidally are an interesting means
      of tracking the effectiveness of residency education. METHODS: Program
      Information Forms from the 94 American Council for Graduate Medical Education
      approved US neurosurgical residency programs were reviewed for the period between
      2000 and 2003. Particular attention was focused on an analysis of the cases
      requiring craniotomy for primary brain tumor and transsphenoidal surgery. The
      mean annual number of primary brain tumor cases per program was 195, with a range
      from 36 to 724 cases. The proportion of primary brain tumors accessed
      transsphenoidally was 20%. The mean annual number of transsphenoidal operations
      performed at academic training centers was 39. A wide range in the frequency of
      transsphenoidal cases from one program to another was also noted. Almost one
      third of training centers performed fewer than 20 transsphenoidal operations
      annually and 80% performed fewer than 50. CONCLUSIONS: Most neurosurgical
      training programs provide residents with excellent experience in craniotomy for
      primary brain tumors. Practice with transsphenoidal surgery, however, is less
      well represented and tends to be clustered at several active centers. The
      implications for neurosurgical education are significant.

PMID- 16304982
TI  - Extracranial-intracranial bypass in the treatment of occlusive cerebrovascular
      disease and intracranial aneurysms in the United States between 1992 and 2001: a
      population-based study.
AB  - OBJECT: The authors assessed the results of extracranial-intracranial (EC-IC)
      bypass surgery in the treatment of occlusive cerebrovascular disease and
      intracranial aneurysms in the US between 1992 and 2001 by using population-based
      methods. METHODS: This is a retrospective cohort study based on data from the
      Nationwide Inpatient Sample (Healthcare Cost and Utilization Project, Agency for
      Healthcare Research and Quality, Rockville, MD). Five hundred fifty-eight
      operations were performed at 158 hospitals by 115 identified surgeons. The
      indications for surgery were cerebral ischemia in 74% of the operations (2.4%
      mortality rate), unruptured aneurysms in 19% of the operations (7.7% mortality
      rate), and ruptured aneurysms in 7% of the operations (21% mortality rate).
      Overall, 4.6% of the patients died and 4.7% of the patients were discharged to
      long-term facilities, 16.4% to short-term facilities, and 74.2% to their homes.
      The annual number of admissions in the US increased from 190 per year (1992-1996)
      to 360 per year (1997-2001), whereas the mortality rates increased from 2.8%
      (1992-1996) to 5.7% (1997-2001). The median annual number of procedures was three
      per hospital (range one-27 operations) or two per surgeon (range one-21
      operations). For 29% of patients, their bypass procedure was the only one
      recorded at their particular hospital during that year; for these institutions
      the mean annual caseload was 0.4 admissions per year. For 42% of patients, their
      particular surgeon performed no other bypass procedure during that year. Older
      patient age (p < 0.001) and African-American race (p = 0.005) were risk factors
      for adverse outcome. In a multivariate analysis in which adjustments were made
      for age, sex, race, diagnosis, admission type, geographic region, medical
      comorbidity, and year of surgery, high-volume hospitals less frequently had an
      adverse discharge disposition (odds ratio 0.54, p = 0.03). CONCLUSIONS: Most EC
      IC bypasses performed in the US during the last decade were performed for
      occlusive cerebrovascular disease. Community mortality rates for aneurysm
      treatment including bypass procedures currently exceed published values from
      specialized centers and, during the period under study, the mortality rates
      increased with time for all diagnostic subgroups. This technically demanding
      procedure has become a very low-volume operation at most US centers.

PMID- 16304983
TI  - Reduced mortality rate in patients with severe traumatic brain injury treated
      with brain tissue oxygen monitoring.
AB  - OBJECT: An intracranial pressure (ICP) monitor, from which cerebral perfusion
      pressure (CPP) is estimated, is recommended in the care of severe traumatic brain
      injury (TBI). Nevertheless, optimal ICP and CPP management may not always prevent
      cerebral ischemia, which adversely influences patient outcome. The authors
      therefore determined whether the addition of a brain tissue oxygen tension (PO2)
      monitor in the treatment of TBI was associated with an improved patient outcome.
      METHODS: Patients with severe TBI (Glasgow Coma Scale [GCS] score < 8) who had
      been admitted to a Level I trauma center were evaluated as part of a prospective
      observational database. Patients treated with ICP and brain tissue PO2 monitoring
      were compared with historical controls matched for age, pathological features,
      admission GCS score, and Injury Severity Score who had undergone ICP monitoring
      alone. Therapy in both patient groups was aimed at maintaining an ICP less than
      20 mm Hg and a CPP greater than 60 mm Hg. Among patients whose brain tissue PO2
      was monitored, oxygenation was maintained at levels greater than 25 mm Hg. Twenty
      five patients with a mean age of 44 +/- 14 years were treated using an ICP
      monitor alone. Twenty-eight patients with a mean age of 38 +/- 18 years underwent
      brain tissue PO2-directed care. The mean daily ICP and CPP levels were similar in
      each group. The mortality rate in patients treated using conventional ICP and CPP
      management was 44%. Patients who also underwent brain tissue PO2 monitoring had a
      significantly reduced mortality rate of 25% (p < 0.05). CONCLUSIONS: The use of
      both ICP and brain tissue PO2 monitors and therapy directed at brain tissue PO2
      is associated with reduced patient death following severe TBI.

PMID- 16304984
TI  - Posttraumatic vasospasm: the epidemiology, severity, and time course of an
      underestimated phenomenon: a prospective study performed in 299 patients.
AB  - OBJECT: The purpose of this prospective study was to evaluate the cumulative
      incidence, duration, and time course of cerebral vasospasm after traumatic brain
      injury (TBI) in a cohort of 299 patients. METHODS: Transcranial Doppler (TCD)
      ultrasonography studies of blood flow velocity in the middle cerebral and basilar
      arteries (VMCA and VBA, respectively) were performed at regular intervals during
      the first 2 weeks posttrauma in association with 133Xe cerebral blood flow (CBF)
      measurements. According to current definitions of vasospasm, five different
      criteria were used to classify the patients: A (VMCA > 120 cm/second); B (VMCA >
      120 cm/second and a Lindegaard ratio [LR] > 3); C (spasm index [SI] in the
      anterior circulation > 3.4); D (VBA > 90 cm/second); and E (SI in the posterior
      circulation > 2.5). Criteria C and E were considered to represent hemodynamically
      significant vasospasm. Mixed-effects spline models were used to analyze the data
      of multiple measurements with an inconsistent sampling rate. Overall 45.2% of the
      patients demonstrated at least one criterion for vasospasm. The patients in whom
      vasospasm developed were significantly younger and had lower Glasgow Coma Scale
      scores on admission. The normalized cumulative incidences were 36.9 and 36.2% for
      patients with Criteria A and B, respectively. Hemodynamically significant
      vasospasm in the anterior circulation (Criterion C) was found in 44.6% of the
      patients, whereas vasospasm in the BA-Criterion D or E-was found in only 19 and
      22.5% of the patients, respectively. The most common day of onset for Criteria A,
      B, D, and E was postinjury Day 2. The highest risk of developing hemodynamically
      significant vasospasm in the anterior circulation was found on Day 3. The daily
      prevalence of vasospasm in patients in the intensive care unit was 30% from
      postinjury Day 2 to Day 13. Vasospasm resolved after a duration of 5 days in 50%
      of the patients with Criterion A or B and after a period of 3.5 days in 50% of
      those patients with Criterion D or E. Hemodynamically significant vasospasm in
      the anterior circulation resolved after 2.5 days in 50% of the patients. The time
      course of that vasospasm was primarily determined by a decrease in CBF.
      CONCLUSIONS: The incidence of vasospasm after TBI is similar to that following
      aneurysmal subarachnoid hemorrhage. Because vasospasm is a significant event in a
      high proportion of patients after severe head injury, close TCD and CBF
      monitoring is recommended for the treatment of such patients.

PMID- 16304985
TI  - Surgical management of adrenocorticotropic hormone-secreting macroadenomas:
      outcome and challenges in patients with Cushing's disease or Nelson's syndrome.
AB  - OBJECT: Adrenocorticotropic hormone (ACTH)-secreting pituitary macroadenomas are
      an uncommon cause of Cushing's disease (CD) and, subsequently, Nelson's syndrome
      (NS). They have been associated with low postoperative remission rates. The
      outcome of modern surgical treatment is unclear and thus was assessed in a series
      of 43 patients, with the goal of improving therapeutic results in patients with
      ACTH-secreting macroadenomas. METHODS: Thirty-seven patients presented with CD
      and six with NS. They represented 15% of the patients surgically treated at the
      authors' institution for ACTH-secreting adenomas. The median patient age was 38
      years (range 14-71 years), and the mean duration of follow up was 37 months
      (range 1-108 months). Remission occurred in 25 (67.6%) of 37 patients with CD,
      whereas the disease persisted in 12 (32.4%) of 37 patients. After an initial
      remission, three (12%) of 25 patients demonstrated signs and symptoms indicative
      of disease recurrence. Among patients with NS, only one (16.6%) displayed
      remission. Invasion of the dura mater by tumor was histologically demonstrated in
      10 patients with CD and in two patients with NS. CONCLUSIONS: Comprehensive
      management of CD caused by ACTH-secreting macroadenomas through the appropriate
      use of combination therapy, including surgery, radiotherapy, radiosurgery, and
      adrenalectomy, can lead to outcomes similar to those for microadenomas. Disease
      recurrence and persistence rates are higher, often because of the invasiveness
      associated with macroadenomas. Remission of NS-associated macroadenomas is
      difficult to achieve. Strategies for the characterization and treatment of
      invasive macroadenomas are needed.

PMID- 16304986
TI  - Primary empty sella syndrome in a series of 142 patients.
AB  - OBJECT: The primary empty sella syndrome (ESS) represents a heterogeneous
      clinical picture characterized by endocrine disturbances and signs of
      intracranial hypertension. An increase in intracranial pressure (ICP) is proposed
      to be one of the involved pathogenetic factors. METHODS: The series included 142
      patients who were observed during a period of 20 years. All patients underwent an
      ICP and cerebrospinal fluid (CSF) dynamics evaluation through the use of a lumbar
      constant-rate infusion test. Impairment of ICP and CSF dynamics was observed in
      109 patients (76.8%). In 35 of the 36 patients affected by severe intracranial
      hypertension without rhinorrhea, improvement in adverse neurological symptoms was
      achieved after implanting a CSF shunt. Visual function, already seriously
      compromised before surgery, remained severely altered in one patient. In the
      group of 34 patients affected by rhinorrhea, CSF leakage was controlled using
      different surgical treatments: CSF shunt placement in 16 cases, surgical repair
      of the sellar floor in three, and both procedures in the remaining 13. Two
      patients refused any surgical treatment. CONCLUSIONS: The role of increased ICP
      in the pathogenesis and perpetuation of primary ESS has been confirmed. Adverse
      neurological signs and a CSF leak are correlated with an actual increase in ICP
      and are relieved after CSF shunt insertion. Cerebrospinal fluid rhinorrhea is
      more common than generally thought. Its resolution can be achieved using a
      careful diagnostic protocol and sometimes may require different surgical
      procedures.

PMID- 16304987
TI  - Rathke cleft cyst intracystic nodule: a characteristic magnetic resonance imaging
      finding.
AB  - OBJECT: The fluid content of Rathke cleft cysts (RCCs) displays variable
      appearances on magnetic resonance (MR) images and can appear indistinguishable
      from other intrasellar or suprasellar cystic lesions. Intracystic nodules
      associated with individual RCCs have been noted, but to date their significance
      has not been fully explored. METHODS: The authors retrospectively reviewed MR
      imaging studies obtained in patients harboring intrasellar or suprasellar lesions
      that were consistent with RCCs to identify the presence and imaging
      characteristics of intracystic nodules. An intracystic nodule was present in nine
      (45%) of 20 patients with an RCC. All intracystic nodules were clearly visible
      and displayed a characteristic low signal intensity on T2-weighted MR images. The
      nodule was only visualized on T1-weighted images in four cases, in which it
      exhibited a consistent high signal intensity similar to that of the cyst fluid.
      The nodules did not enhance following the intravenous administration of a
      contrast agent. CONCLUSIONS: Although it is difficult to differentiate RCCs from
      other sellar cystic lesions because of the variable signal intensities displayed
      on MR images, the intensity of the intracystic nodule seems consistent on T1- and
      T2-weighted images, and the nodule is always clearly visible on T2-weighted
      images. With a nonenhancing cystic lesion that does not cause significant
      symptoms in the patient, the identification of an intracystic nodule with a
      characteristic signal intensity will aid in the diagnosis of RCC and the
      selection of conservative management.

PMID- 16304988
TI  - Depression and functional outcome in patients with brain tumors: a population
      based 1-year follow-up study.
AB  - OBJECT: The authors analyzed changes in depression and contemporary functional
      states by using valid tools in a population-based study sample during a 1-year
      follow-up period. METHODS: The study population consisted of 77 patients with a
      solitary primary brain tumor treated surgically at the Oulu Clinic for
      Neurosurgery. Each patient's depressive status, according to the Beck Depression
      Inventory (BDI), and functional outcome, based on the Karnofsky Performance Scale
      (KPS), were evaluated before the tumor was surgically treated as well as 3 months
      and 1 year after surgery. Before surgery 27 patients (35%) had BDI scores
      indicating the presence of depression. These scores were significantly higher in
      patients with a history of depression (p = 0.017) and in those with a lower
      functional outcome (p = 0.015). In the entire study sample the severity of
      depression decreased statistically significantly (p = 0.031) at 3 months
      postsurgery. A lower functional status (KPS score < or = 70) in patients was
      significantly associated with high depression scores at the 3-month (p = 0.000)
      and 1-year (p = 0.005) assessments. The decrease in the level of depression was
      significant in patients with an anterior tumor (p = 0.049) and those with a
      pituitary adenoma (p = 0.019). CONCLUSIONS: Affective disorders among patients
      with brain tumors must be considered immediately after surgery, especially in
      persons with a depression history and in those with a coincident physical
      disability.

PMID- 16304989
TI  - Use of a simple intraoperative hydrostatic pressure test to assess the
      relationship between mobility of the ventricular stoma and success of third
      ventriculostomy.
AB  - OBJECT: Neuroendoscopists often note pulsatility or flabbiness of the floor of
      the third ventricle during endoscopic third ventriculostomy (ETV) and believe
      that either is a good indication of the procedure's success. Note, however, that
      this belief has never been objectively measured or proven in a prospective study.
      The authors report on a simple test-the hydrostatic test-to assess the mobility
      of the floor of the third ventricle and confirm adequate ventricular flow. They
      also analyzed the relationship between a mobile floor (a positive hydrostatic
      test) and prospective success of ETV. METHODS: During a period of 3 years between
      July 2001 and July 2004, 30 ETVs for obstructive hydrocephalus were performed in
      22 male and eight female patients. Once the stoma had been created, the
      irrigating Ringer lactate solution was set at a 30-cm height from the external
      auditory meatus, and the irrigation valve was opened while the other ports on the
      endoscope were closed. The ventricular floor ballooned downward and stabilized.
      The irrigation valve was then closed and ports of the endoscope were opened. The
      magnitude of the upward displacement of the floor was then assessed. Funneling of
      the stoma was deemed to be a good indicator of floor mobility, adequate flow, and
      a positive hydrostatic test. All endoscopic procedures were recorded using
      digital video and recordings were subsequently assessed separately by two blinded
      experienced neuroendoscopists. Patients underwent prospective clinical follow up
      during a mean period of 11.2 months (range 1 month-3 years), computerized
      tomography and/or magnetic resonance imaging studies of the brain, and
      measurements of cerebrospinal fluid pressure through a ventricular reservoir when
      present. Failure of ETV was defined as the subsequent need for shunt
      implantation. The overall success rate of the ETV was 70% and varied from 86.9%
      in patients with a mobile stoma and a positive hydrostatic test to only 14.2% in
      patients with a poorly mobile floor and a negative test (p < 0.05). The positive
      predictive value of the hydrostatic test was 86.9%, negative predictive value
      85.7%, sensitivity 95.2%, and specificity 66.6%. CONCLUSIONS: The authors
      concluded that the hydrostatic test is an easy, brief test. A positive test
      result confirms a mobile ventricular floor and adequate flow through the created
      ventriculostomy. Mobility of the stoma is an important predictor of ETV success
      provided that there is no obstruction at the level of the arachnoid granulations
      or venous outflow. A thin, redundant, mobile third ventricle floor indicates a
      longstanding pressure differential between the third ventricle and the basal
      cisterns, which is a crucial factor for ETV success. A positive hydrostatic test
      may avert the need to insert a ventricular reservoir, thus avoiding associated
      risks of infection.

PMID- 16304990
TI  - A reassessment of vascular endothelial growth factor in central nervous system
      pathology.
AB  - Overexpression of vascular endothelial growth factor (VEGF) is associated with
      several central nervous system (CNS) diseases and abnormalities, and is often
      postulated as a causative factor and promising therapeutic target in these
      settings. The authors' goal was to reassess the contribution of VEGF to the
      biology and pathology of the CNS. The authors review the literature relating to
      the following aspects of VEGF: 1) the biology of VEGF in normal brain; 2) the
      involvement of VEGF in CNS disorders other than tumors (traumatic and ischemic
      injuries arteriovenous malformations, inflammation); and 3) the role of VEGF in
      brain tumor biology (gliomas and the associated vasogenic edema, and
      hemangioblastomas). The authors conclude the following: first, that VEGF
      overexpression contributes to the phenotype associated with many CNS disorders,
      but VEGF is a reactive rather than a causative factor in many cases; and second,
      that use of VEGF as a therapeutic agent or target is complicated by the effects
      of VEGF not only on the cerebral vasculature, but also on astrocytes, neurons,
      and inflammatory cells. In many cases, therapeutic interventions targeting the
      VEGF/VEGF receptor axis are likely to be ineffective or even detrimental.
      Clinical manipulation of VEGF levels in the CNS must be approached with caution.

PMID- 16304991
TI  - Power Doppler imaging in detection of surgically induced indirect neoangiogenesis
      in adult moyamoya disease.
AB  - OBJECT: Moyamoya is a rare, chronic disease that leads to the progressive
      narrowing and/or occlusion of the distal internal carotid and proximal cerebral
      arteries. Chronic cerebral ischemia ensues due to insufficient collateral blood
      supply. One potential treatment consists of the restoration of regional cerebral
      blood flow by direct or indirect revascularization surgery. The extent of
      neovascularization, especially in indirect procedures such as
      encephalomyosynangiosis (EMS), is currently evaluated with conventional
      angiography. Because this method is invasive and carries some risks, the authors
      investigated power Doppler imaging as an alternative noninvasive bedside
      procedure that can be used to assess surgically induced indirect
      revascularization in adult patients with moyamoya disease. METHODS: Twelve
      symptomatic patients with adult moyamoya disease (seven women and five men, mean
      age 38 +/- 17 years) underwent combined (direct and indirect) revascularization.
      They were then examined using conventional angiography and power Doppler imaging
      to assess the extent of revascularization within 120 days postsurgery. According
      to the number of intracranial vessels demonstrating opacification on conventional
      angiography and power Doppler imaging studies, EMS was graded as follows: 1,
      absent (0 vessels); 2, moderate (one-four vessels); and 3, extensive (> four
      vessels) for both methods. Examiners were blinded to the classification results
      for the procedure that they did not grade. All 24 hemispheres were examined. The
      visual grading of EMS revealed a highly significant agreement between
      conventional angiography and power Doppler imaging (Spearman rank coefficient, r
      = 0.92; p < 0.001) and there was 100% agreement of patency of the bypass between
      the direct and indirect methods. CONCLUSIONS: The authors found excellent
      agreement between the two methods. Therefore, power Doppler imaging is a valid
      noninvasive alternative to carotid artery angiography in evaluating direct and
      indirect revascularization.

PMID- 16304993
TI  - Enhanced brain angiogenesis in chronic cerebral hypoperfusion after
      administration of plasmid human vascular endothelial growth factor in combination
      with indirect vasoreconstructive surgery.
AB  - OBJECT: Vascular endothelial growth factor (VEGF) is a secreted mitogen
      associated with angiogenesis. The conceptual basis for therapeutic angiogenesis
      after plasmid human VEGF gene (phVEGF) transfer has been established in patients
      presenting with limb ischemia and myocardial infarction. The authors hypothesized
      that overexpression of VEGF using a gene transfer method combined with indirect
      vasoreconstruction might induce effective brain angiogenesis in chronic cerebral
      hypoperfusion, leading to prevention of ischemic attacks. METHODS: A chronic
      cerebral hypoperfusion model induced by permanent ligation of both common carotid
      arteries in rats was used in this investigation. Seven days after induction of
      cerebral hypoperfusion, encephalomyosynangiosis (EMS) and phVEGF administration
      in the temporal muscle were performed. Fourteen days after treatment, the VEGF
      gene therapy group displayed numbers and areas of capillary vessels in temporal
      muscles that were 2.2 and 2.5 times greater, respectively, in comparison with the
      control group. In the brain, the number and area of capillary vessels in the
      group treated with the VEGF gene were 1.5 and 1.8 times greater, respectively,
      relative to the control group. CONCLUSIONS: In rat models of chronic cerebral
      hypoperfusion, administration of phVEGF combined with indirect vasoreconstructive
      surgery significantly increased capillary density in the brain. The authors'
      results indicate that administration of phVEGF may be an effective therapy in
      patients with chronic cerebral hypoperfusion, such as those with moyamoya
      disease.

PMID- 16304992
TI  - Expression of the tumor necrosis factor receptor-associated factors 1 and 2 and
      regulation of the nuclear factor-kappaB antiapoptotic activity in human gliomas.
AB  - OBJECT: Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) are a
      recently established group of proteins involved in the intracellular signaling of
      the TNFR superfamily members. The TRAFs have been implicated in promoting cell
      survival through the activation of transcription factor nuclear factor (NF)
      kappaB. The authors investigated the expression of NF-kappaB, caspase 3, TRAF1,
      TRAF2, and TRAF-associated NF-kappaB activator/TRAF-interacting protein (TANK/I
      TRAF), a regulator of TRAF activity, in human gliomas. METHODS: Tumor samples
      were obtained in 27 adult patients harboring seven low-grade gliomas, nine
      anaplastic astrocytomas, and 11 glioblastomas multiforme. The NF-kappaB
      activation was analyzed using the electrophoresis mobility shift assay; TRAF1,
      TRAF2, TANK/I-TRAF, and caspase 3 expression were studied using Western blot
      analysis. Upregulated NF-kappaB DNA-binding activity, compared with that in
      normal brain tissue, was detected in all tumor samples (p = 0.002). The level of
      NF-kappaB activity showed some correlation with World Health Organization tumor
      grades (p = 0.01), even though variable activity levels were demonstrated in
      relation to tissue heterogeneity, which resulted in a substantial number of
      outliers in the quantitative analysis. Increased levels of TRAF1, TRAF2, and
      TANK/ I-TRAF were expressed in astrocytomas compared with levels in normal brain
      tissue (p = 0.02, 0.006, and 0.01, respectively). CONCLUSIONS: Data in this study
      confirm the upregulation of NF-kappaB in gliomas and reveal a correlation between
      levels of this transcription factor and tumor grade. A constitutive expression of
      TRAF1, TRAF2, and TANK/I-TRAF in human gliomas was documented. These proteins are
      involved in the intracellular signal transduction of the TNFR superfamily and in
      the control of NF-kappaB expression and its antiapoptotic activity.

PMID- 16304994
TI  - Flow changes caused by the sequential placement of stents across the neck of
      sidewall cerebral aneurysms.
AB  - OBJECT: The goal of this study was to quantify the reduction in velocity,
      vorticity, and shear stresses resulting from the sequential placement of stents
      across the neck of sidewall cerebral aneurysms. METHODS: A digital particle image
      velocimetry (DPIV) system was used to measure the pulsatile velocity field within
      a flexible silicone sidewall intracranial aneurysm model and at the aneurysm neck
      parent artery interface in this model. The DPIV system is capable of providing an
      instantaneous, quantitative two-dimensional measurement of the velocity vector
      field of "blood" flow inside the aneurysm pouch and the parent vessel, and its
      changes at varying stages of the cardiac cycle. The corresponding vorticity and
      shear stress fields are then computed from the velocity field data. Three
      Neuroform stents (Boston Scientific/Target), each with a strut thickness between
      60 and 65 microm, were subsequently placed across the neck of the aneurysm model
      and measurements were obtained after each stent had been placed. The authors
      measured a consistent decrease in the values of the maximal averaged velocity,
      vorticity, and shear stress after placing one, two, and three stents.
      Measurements of the circulation inside the sac demonstrated a systematic
      reduction in the strength of the vortex due to the stent placement. The decrease
      in the magnitude of the aforementioned quantities after the first stent was
      placed was remarkable. Placement of two or three stents led to a less significant
      reduction than placement of the first stent. CONCLUSIONS: The use of multiple
      flexible intravascular stents effectively reduces the strength of the vortex
      forming in an aneurysm sac and results in a decrease in the magnitude of stresses
      acting on the aneurysm wall.

PMID- 16304995
TI  - Ultrastructural characteristics of hemorrhagic, nonhemorrhagic, and recurrent
      cavernous malformations.
AB  - OBJECT: Ultrastructural characteristics of hemorrhagic, nonhemorrhagic, primary,
      and recurrent central nervous system cavernous malformations (CMs) were examined
      in an attempt to clarify their pathological mechanisms. METHODS: Thirteen
      specimens (nine from samples of CMs and four from healthy control tissue) were
      processed for ultrastructural study immediately after surgical or postmortem
      removal, by fixation in glutaraldehyde/formalin and postfixation in OsO4.
      Transmission electron microscopy was used to examine the vascular walls,
      endothelium, subendothelium, and cytoplasmic organelles. The vascular walls in
      CMs demonstrated abnormal ultrastructure with no basement membranes and
      astrocytic foot processes. Pericytes were rarely seen. Single-layer lining
      endothelial cells showed fenestrated luminal surfaces. Large gaps were observed
      at intercellular junctions between endothelial cells, and large vesicles with
      extremely thin plasma membranes bordering the lumen were common in the lesions
      that had previously hemorrhaged. Endothelial cells of recurrent CMs had more
      Weibel-Palade bodies, filopodia, cytoplasmic processes, micropinocytotic
      vesicles, and filaments than those in primary lesions and normal control tissues.
      CONCLUSIONS: The absence of the blood-brain barrier, normal supporting wall
      structure, and large vesicles bordering the lumen of CM vessels may explain
      leakage of red blood cells into surrounding brain in the absence of major
      hemorrhage. Proliferation of residual abnormal endothelial cells may contribute
      to the recurrence of surgically removed CMs.

PMID- 16304996
TI  - Functional magnetic resonance imaging in adult craniopagus for presurgical
      evaluation.
AB  - Cranially conjoined twins are rare and pose unique challenges in the preoperative
      evaluation of cerebral language function. The authors report on their experience
      in the functional magnetic resonance (fMR) imaging evaluation of adult
      craniopagus (temporoparietooccipital fusion) to evaluate hemispheric language
      dominance and the eloquent language areas in the preoperative planning stages.
      Conventional clinical imaging hardware originally designed for individuals was
      adapted and tailored for use in the twins. They were assigned a selection of
      language tasks while undergoing fMR imaging. Significant blood oxygen level
      dependent activations were detected in the main language regions in each twin,
      that is, the inferior frontal gyrus (around the Broca area), the middle and
      superior temporal lobes (around the Wernicke area) together with the inferior
      parietal lobe, and the middle and superior frontal gyri. Overall, the right
      handed twin was strongly left lateralized for language, whereas the left-handed
      twin showed more bilateral activation during language tasks. Noninvasive language
      mapping with the aid of fMR imaging has been demonstrated for the first time in
      total craniopagus.

PMID- 16304997
TI  - Entrapment neuropathy of the optic nerve due to hyperostosis associated with
      congenital anemia.
AB  - The authors report on the case of a 14-year-old boy who presented with bilateral
      visual impairment due to optic canal stenosis caused by hyperplasia of the bone
      marrow arising from anemia. The patient had hereditary hemolytic anemia with
      unstable hemoglobin of the Christchurch type. This congenital form of anemia
      caused hyperplasia of the bone marrow as well as hyperostosis of the entire
      calvarial bone, which in turn led to optic canal stenosis. The patient underwent
      surgical decompression of the optic canal, resulting in significant improvement
      in visual acuity. Pathological findings in the calvarial bone indicated
      hypertrophic bone marrow with no other specific features such as neoplastic
      pattern or fibrous dysplasia. With the exception of objective hearing impairment,
      no other significant cranial neuropathy has been detected thus far. On reviewing
      the published literature, this case was found to be the first in which
      hyperostosis due to congenital anemia resulted in symptomatic entrapment
      neuropathy of the optic nerve. The authors concluded that surgical decompression
      effectively improves visual acuity.

PMID- 16304998
TI  - Endoscope-assisted microsurgical resection of an intraneural ganglion cyst of the
      hypoglossal nerve.
AB  - An unusual case of an intraneural ganglion cyst of the hypoglossal nerve is
      presented. Only one case of this rare clinical entity has been reported
      previously. A 51-year-old woman presented with a 6-month history of left-sided
      hypoglossal nerve palsy. Magnetic resonance imaging revealed a cystic lesion
      related to the hypoglossal canal. There was no enhancement of the lesion after
      administration of Gd. A high-resolution computerized tomography scan of the skull
      base demonstrated an enlargement of the hypoglossal canal. To access the lesion,
      a far-lateral endoscope-assisted microsurgical approach was used. An intraneural
      ganglion lesion invading the hypoglossal nerve was found and resected. A
      histopathological examination confirmed that the lesion was an intraneural
      ganglion cyst. The occurrence of an intraneural ganglion cyst at the hypoglossal
      nerve is very rare. This case exemplifies an atypical location of a synovial cyst
      with cranial nerve involvement.

PMID- 16304999
TI  - Reflux-free cannula for convection-enhanced high-speed delivery of therapeutic
      agents.
AB  - OBJECT: Clinical application of the convection-enhanced delivery (CED) technique
      is currently limited by low infusion speed and reflux of the delivered agent. The
      authors developed and evaluated a new step-design cannula to overcome present
      limitations and to introduce a rapid, reflux-free CED method for future clinical
      trials. METHODS: The CED of 0.4% trypan blue dye was performed in agarose gel to
      test cannula needles for distribution and reflux. Infusion rates ranging from 0.5
      to 50 microl/minute were used. Agarose gel findings were translated into a study
      in rats and then in cynomolgus monkeys (Macacafascicularis) by using trypan blue
      and liposomes to confirm the efficacy of the reflux-free step-design cannula in
      vivo. Results of agarose gel studies showed reflux-free infusion with high flow
      rates using the step-design cannula. Data from the study in rats confirmed the
      agarose gel findings and also revealed increasing tissue damage at a flow rate
      above 5-microl/minute. Robust reflux-free delivery and distribution of liposomes
      was achieved using the step-design cannula in brains in both rats and nonhuman
      primates. CONCLUSIONS: The authors developed a new step-design cannula for CED
      that effectively prevents reflux in vivo and maximizes the distribution of agents
      delivered in the brain. Data in the present study show reflux-free infusion with
      a constant volume of distribution in the rat brain over a broad range of flow
      rates. Reflux-free delivery of liposomes into nonhuman primate brain was also
      established using the cannula. This step-design cannula may allow reflux-free
      distribution and shorten the duration of infusion in future clinical applications
      of CED in humans.

PMID- 16305000
TI  - Mapping prosody: correlation of functional magnetic resonance imaging with
      intraoperative electrocorticography recordings in a patient with a right-sided
      temporooccipital glioma. Case illustration.

PMID- 16305001
TI  - Cystic cavernous malformation of the cerebellopontine angle. Case illustration.

PMID- 16305002
TI  - Posttraumatic migraine.

PMID- 16305003
TI  - Cerebellopontine angle meningiomas.

PMID- 16305004
TI  - The inhibitory effect of an arginine bicarbonate/calcium carbonate CaviStat
      containing dentifrice on the development of dental caries in Venezuelan school
      children.
AB  - OBJECTIVE: This study assessed the effect of an arginine bicarbonate/calcium
      carbonate (CaviStat)-containing dentifrice on caries development, mainly in 11-
      to 12-year-old Venezuelan children over a two-year period. METHODOLOGY: Children
      (726) with a DMFT between 3 and 6 were examined at baseline, six months, and one
      and two years using a mirror, probe, and DMFS scoring. Subjects who completed the
      study consisted of two groups; 304 test and 297 control. The test group received
      a CaviStat-containing dentifrice, and the controls used a commercially available
      1100 ppm fluoride toothpaste. All subjects were instructed to brush three times a
      day for 1 minute followed by swishing for 30 seconds. RESULTS: After six months,
      the mean DMFS scores increased only slightly from baseline in both groups, 6.93
      +/- 0.22 in the control and 6.59 +/- 0.22 in the test subjects. After one year,
      the mean DMFS score in the control group rose to 8.00 +/- 0.24 and leveled off at
      7.92 +/- 0.30 at two years. In contrast, the mean DMFS score in the test group
      decreased to 5.50 +/- 0.24 after one year before rising to 6.99 +/- 0.28 at two
      years. DMFS difference between the two groups was highly significant (p < 0.001),
      but mainly due to the large difference seen at one year. Dissection of the data
      showed that the erupted first molars dominated the overall DMFS changes. At the
      beginning of this study, first molar scores started at high values and showed a
      pattern thereafter like that seen for the total data. In contrast,
      premolars/molars, which erupt 4-6 years later (and at the start of the study had
      a mean DMFS score slightly above zero), showed a clear rise in the DMFS score in
      the control group during the first year of the study, which continued to rise
      until the end of the investigation. In contrast, the CaviStat group showed no
      change in the premolar/second molar DMFS score from baseline during the first
      year (giving the impression of 100% inhibition at one year), but showed a delayed
      rise thereafter that paralleled that seen in the controls between one and two
      years (58.3% inhibition at two years). Reversal of the development of early
      dental caries lesions in the CaviStat subjects and limitations of the diagnosis
      of very early caries lesions with standard dental explorers was suggested for the
      interesting first molar, first year data. Inhibition of caries initiation and
      caries progression in the CaviStat group was also observed and easier to see in
      the premolar/second molar, second year data where the DMFS scores were very low
      at baseline and reversals are not a significant issue. The results were subjected
      to statistical analysis including analysis of covariance. Largely because of the
      first year and first molar data, the difference between control and experimental
      groups was highly significant (p < 0.001). Similar comparison with the later
      erupting premolar/molar teeth showed the CaviStat effect was also significant but
      at a lower level (p < 0.05). The differences could not be due to examiner error
      since the Kappa for 10% of the subjects randomly selected and re-examined was
      0.898 overall and 0.914 for the first molar data. The data also suggested
      CaviStat inhibition of caries progression because of a slower rate of rise of
      missing+filled teeth in the CaviStat vs. the control group (p < 0.05).
      CONCLUSION: A CaviStat-containing toothpaste was more effective both clinically
      and statistically in inhibiting caries initiation and progression than the
      fluoride toothpaste control, and manifested its effects differently in the
      already-erupted first molars than in the later-erupting premolars and second
      molars.

PMID- 16305005
TI  - Comparison of irrigation to floss as an adjunct to tooth brushing: effect on
      bleeding, gingivitis, and supragingival plaque.
AB  - OBJECTIVE: The purpose of this twenty-eight day, randomized, single-blind
      clinical trial was to assess the efficacy of the addition of daily oral
      irrigation to both power and manual tooth brushing, compared to a traditional
      regimen of manual tooth brushing and flossing, to determine which regimen had the
      greatest effect on the reduction of gingival bleeding, gingivitis, and
      supragingival plaque. METHODOLOGY: The study was designed for a total of 105
      subjects to participate in a twenty-eight day trial, with 35 subjects randomly
      assigned to one of three groups: Group 1-manual toothbrush and floss; Group 2
      manual toothbrush and dental water jet; and Group 3-sonic toothbrush and dental
      water jet. All subjects received written and verbal instructions for using their
      regimens. Subjects were asked to brush for a timed two minutes, twice per day,
      with the brush and the dentifrice provided, and to refrain from using any
      additional oral hygiene aids. Subjects using the dental water jet were instructed
      to use the water jet on a medium setting, irrigating once per day with 500 ml of
      luke warm water. Subjects using the dental floss were instructed to use the floss
      once daily. Subjects were examined by two calibrated examiners, and data were
      collected at baseline (BSL), 14 days (D14), and 28 days (D28). Subjects were
      asked to abstain from any oral hygiene for 12 hours prior to each study visit.
      Subjects were scored using the Carter and Barnes Bleeding Index, Loe and Silness
      Gingival Index, and the Proximal/Marginal Plaque Index. Mean scores on the three
      indices for the three groups were used for statistical analysis at each time
      point. Additionally, the means were used for comparisons as change from baseline
      and percent change from baseline at D14 and D28. The significance of percentage
      change in each index from baseline to D14 and D28 was evaluated using a one
      tailed t-test. Significant differences are reported at alpha < or = 0.05 for
      these planned group comparisons. RESULTS: Thirty-one subjects in Group 1, 32
      subjects in Group 2, and 32 subjects in Group 3 completed the study. Bleeding
      Index: Groups 2 and 3, the irrigation groups, were statistically significantly
      more effective than Group 1 in reducing the bleeding index at D14 and D28,
      whether measured by mean reduction or percentage reduction. Gingival Index: At
      D14, both irrigation groups demonstrated a statistically significantly greater
      reduction in the gingival index compared to brushing and flossing for the facial
      surfaces. There was no significant difference between groups for the lingual
      surface at D14. At D28 there was a significant difference between Groups 1 and 2
      for both the facial and lingual surfaces. Plaque Index: There was one significant
      difference between groups for the plaque index measured on the lingual surfaces.
      The manual toothbrush and floss were less effective than the sonic toothbrush and
      irrigation. Group 3 was also significantly better than Group 1 in reducing the
      plaque index on the facial surfaces at both D14 and D28. On plaque percentage
      reduction on the facial surface, Group 2 was significantly better than Group 1 at
      D14. There was no statistical difference between Group 1 and Group 2 at D28.
      CONCLUSION: The results of this clinical trial indicate that when combined with
      manual or sonic tooth brushing, oral irrigation is an effective alternative to
      manual tooth brushing and dental floss for reducing bleeding, gingival
      inflammation, and plaque removal.

PMID- 16305006
TI  - Tooth whitening: tooth color changes following treatment by peroxide and light.
AB  - OBJECTIVE: This study examined the use of color measurement to determine tooth
      color in a study of bleaching with peroxide and light used separately and in
      combination. Two measurement protocols were evaluated for their ability to reveal
      differences between treatments and confirm tooth shade evaluations. METHODOLOGY:
      Before and after treatment, 43 subjects were evaluated for tooth color using a
      shade guide and a chromameter. Two measurement procedures were used: one measured
      a single location on each tooth using a fabricated plastic stent, and the other
      measured nine locations across the buccal surface. Values from the two procedures
      were compared to each other, and to shade guide measurements. RESULTS: Tooth
      color, as measured by both procedures, significantly correlated with shade
      evaluation. Statistically significant differences between treatment groups were
      found more often with data from the multiple-site procedure than from the single
      site procedure. Incisal-gingival color gradation on tooth surfaces was diminished
      as a result of whitening treatments. Chromameter measurement data showed that
      tooth whitening procedures reduced tooth yellowness (b) more reproducibly than
      they increased whiteness (L). CONCLUSION: When more sites per surface were
      measured, tooth color measurement by the chromameter more closely matched shade
      with less variability and greater statistical power. Chromameter-derived values
      can be used to estimate shade values to a reasonable level of accuracy.
      Decreasing yellowness, particularly at the gingival margin, was an important
      component of the tooth whitening effect. Following tooth whitening, teeth were
      more uniform in their color, and this may contribute substantially to the
      subjective patient recognition of whiter teeth.

PMID- 16305007
TI  - Plaque removal with an experimental chewable toothbrush and a control manual
      toothbrush in a care-dependent elderly population: a pilot study.
AB  - OBJECTIVE: Oral hygiene and oral health are major concerns for care-dependent
      elderly persons. The objective of this study was to examine the plaque removal
      efficacy of a novel experimental chewable toothbrush used by the subjects
      themselves. METHODOLOGY: Fourteen subjects whose oral care was usually provided
      by caregivers in nursing facilities were enrolled in a two-phase, crossover
      study. The study was designed to evaluate plaque removal following a single
      brushing with either an experimental chewable toothbrush used by the subjects
      themselves, or a control manual toothbrush used by caregivers on the subjects.
      Plaque removal was assessed according to the plaque index of Silness and Loe.
      RESULTS: The overall plaque scores were significantly reduced from 2.14 +/- 0.53
      to 1.23 +/- 0.39 using the experimental brush, and from 2.08 +/- 0.43 to 1.22 +/-
      0.17 using the control brush (p < 0.05). Relative plaque reduction was 41.0 +/-
      17.6% for the experimental brush group and 38.8 +/- 16.6% for the control brush
      group, with no significant difference between the two brushes (p = 0.84). On
      lingual tooth surfaces, the experimental brush showed a plaque reduction of 68.8
      +/- 13.7% compared to 38.4 +/- 22.9% with the control brush, and the difference
      was statistically significant (p = 0.011). The chewable toothbrushes were
      harmless and acceptable to the subjects. CONCLUSION: The experimental brush was
      able to remove a significant amount of plaque, particularly on the lingual
      surfaces, demonstrating its effectiveness for plaque removal when used by care
      dependent elderly.

PMID- 16305008
TI  - Clinical evaluations of sustained calculus control by Colgate Simply White
      dentifrice using an in-situ appliance.
AB  - OBJECTIVE: Two clinical studies were conducted to evaluate the dental calculus
      control efficacy of Colgate Simply White dentifrice versus a positive and a
      negative control dentifrice, using a published intra-oral appliance and
      monitoring the prevention of calcium deposition, an indicator of early dental
      calculus formation. METHODOLOGY: Healthy human volunteers entered into the two
      double-blind, cross-over studies. An intra-oral appliance was custom-made for
      each subject. After brushing with an assigned dentifrice, each subject wore his
      or her appliance for four daytime hours (study 1) or 12 overnight hours (study
      2). When the appliance was removed, it was washed, suspended in 0.1 M HCl to
      release Ca++ from deposits, and analyzed by Inductively Coupled Plasma (ICP) for
      deposited calcium. The three dentifrices studied were Colgate Simply White (CSW),
      Colgate Regular dentifrice (CR), and Colgate Tartar Control Whitening (CTW).
      There was a one-week wash-out period between each product use. RESULTS: There
      were no side effects observed or reported in either study. In both the four- and
      12-hour studies, CSW and CTW had significantly lower calcium uptake compared to
      CR (p < 0.05). There was no statistical difference between CSW and CTW in
      efficacy. CONCLUSION: The results of this research demonstrate that Colgate
      Simply White dentifrice provides four- and 12-hour calculus control efficacy,
      superior to a standard dentifrice and comparable to a commercial anti-tartar
      dentifrice.

PMID- 16305009
TI  - Randomized controlled trial of 10% hydrogen peroxide whitening strips.
AB  - OBJECTIVE: This research compared the clinical response of two different peroxide
      containing gel formulations delivered using self-applied whitening strips.
      METHODOLOGY: A randomized, double-blind clinical trial was conducted to compare a
      one-week 10% hydrogen peroxide thin (0.13 mm) bleaching gel (Crest Whitestrips
      Premium) to a marketed two-week 6% hydrogen peroxide strip (0.20 mm) control
      (Crest Whitestrips). The maxillary arch was treated twice daily for 30 minutes.
      Efficacy (L*a*b* color change) was measured objectively by digital image analysis
      after one and two weeks. RESULTS: A total of 40 adults ranging from 19-48 years
      of age participated in the study. Both treatments were effective in whitening
      teeth, as evidenced by a statistically significant improvement from baseline (p <
      0.001) beginning at one week. At that time, the adjusted mean deltab* (SE)
      (yellowness reduction) for the 10% strip was -2.42 (0.147) compared to -1.91
      (0.143) for the 6% strip, with the treatments differing significantly (p = 0.02).
      At two weeks, the adjusted mean deltab* (SE) for the 10% strip was -3.31 (0.182)
      compared to -2.49 (0.167) for the control. After two weeks, treatments differed
      significantly (p < 0.02) for deltab* and deltaL* (lightness improvement).
      Comparing results from two weeks of the 6% control strip to one week of the 10%
      strip, the mean deltab* treatment difference was -0.07 (90% confidence interval
      from -0.44 to +0.31). Both treatments were generally well tolerated, with mild
      and transient tooth sensitivity or oral irritation representing the most common
      adverse events. CONCLUSION: Vital bleaching with 10% hydrogen peroxide strips at
      one week was as effective as 6% hydrogen peroxide strips used for two weeks.

PMID- 16305010
TI  - Grassroots armada for suicide prevention.

PMID- 16305011
TI  - When a brain injury may explain a patient's symptoms.

PMID- 16305012
TI  - A process model for managing national accreditation.

PMID- 16305013
TI  - Searching for a message to unite professionals and the public.

PMID- 16305014
TI  - Parity: states lead the way, despite implementation challenges.

PMID- 16305015
TI  - Consumer-directed care: static or buzz?

PMID- 16305016
TI  - The business of recovery.

PMID- 16305017
TI  - Care management for both the patient and the workforce.

PMID- 16305018
TI  - ["Who belongs to your family"].

PMID- 16305019
TI  - [Social support in suicide forums].
AB  - Suicide forums--interactive forums on the Internet--are attractive to suicidal
      youth. The question if participation in these forums might be dangerous (because
      of imitation and contagion) or if it should be considered as helpful (being a
      chance to talk openly with others) is still discussed controversely. Mutual
      social support seems to be an important factor. By means of an online survey in
      German suicide forums and a content analysis of forum postings, we gathered
      information about this subject. Selected results from our study are presented in
      this paper. Social support in suicide forums is rated as high as support from
      friends and higher than support from family. Social support is higher in suicide
      forums where discussion of suicide methods does not occur. Higher social support
      in suicide forums correlates with participants' ratings of reduction of
      suicidality. Furthermore, some information about the contents of communication in
      suicide forums will be given, based on the results of the content analysis.
      Results are discussed regarding the potential risks of these forums.

PMID- 16305020
TI  - [www.hungrig-online.de: results from an online survey in the largest German
      speaking Internet self help community for eating disorders].
AB  - Being a medium which is available anywhere and at any time, the Internet is an
      appropriate contact point for people with psychological or somatic disorders.
      With this objective, www.hungrig-online.de was established in 1999. It provides
      information and communication for people affected by an eating disorder. Today,
      the website is the largest german-speaking Internet portal for eating disorders.
      In this investigation, 1006 participants were asked about socio-demographic data,
      details about their eating disorder and their attitudes and expectations
      concerning hungrig-on-line.de. The answers of the 312 13-to-19-year-old
      participants are more precisely analysed in this article. They evaluated the
      offerings of hungrig-online.de mostly positively.

PMID- 16305021
TI  - [www.drugcom.de--an Internet based information and counselling project for the
      prevention of addiction].
AB  - The Internet based addiction prevention project www.drugcom.de of the Federal
      Centre of Health Education (BZgA) offers information and anonymous counselling
      for adolescents and young adults. The Internet project is based on a secondary
      preventive approach. The objective is to prevent misuse and addiction of
      substances/drugs and to reduce negative effects of consumption (risk competence).
      The effects of the project are on different levels: Transfer of knowledge and
      change of attitude and behaviour. The process evaluation is based on quantitative
      data from online questionnaires on the website and on the log file analysis of
      users, use and acceptance. According to the different sections of www.drugcom.de
      that the user has been visiting, different indicators are raised, e.g.
      comprehensibility of text, satisfaction with counselling service, completeness of
      information etc. In 2004 the number of visits per day compared with the previous
      year has almost doubled to more than at an average of 1,000 per day. Consumers of
      legal and illegal drugs build the majority of drugcom users. Their average age is
      20 years. 79% of those asked have consumed an illegal substance once in their
      life as a minimum, mostly cannabis. The knowledge tests and the self test
      concerning alcohol are used especially often. The results show that it is
      possible to reach the target group of drug consuming young people by an Internet
      based service. The Internet project www.drugcom.de as an online-service of
      addiction prevention has been established with success.

PMID- 16305023
TI  - [Biological rhythms].

PMID- 16305022
TI  - [Violent computergames: distribution via and discussion on the Internet].
AB  - The spread and use of computer-games including (interactive) depictions of
      violence are considered a moral problem, particularly if played by children and
      youths. This essay expresses an opinion on H. Volper's (2004) demand of
      condemning certain contents by media ethics. At the same time, an overview on the
      spread and use of "violent games" by children and youths is offered. As a matter
      of fact, the share of these titles in the complete range must not be estimated
      too high, certain titles on the other hand are extremely wide-spread. Finally,
      Fritz's and Fehr's thesis of the cultural conflict "computer game" (2004) is
      discussed, demonstrated at the example of the discussion on the Internet, and on
      the basis of this thesis a mediating position between the two cultures including
      audience ethics (Funiok 1999) is presented.

PMID- 16305024
TI  - [Conduct disorders... a new expertise that arouses passions!].

PMID- 16305025
TI  - [Measures to favor a three-year old and the presence of parents near the gravely
      ill child].

PMID- 16305026
TI  - [Restless adolescents, the places they miss].

PMID- 16305027
TI  - [Adolescent health in France].

PMID- 16305028
TI  - [Music heals, soothes, relieves...].

PMID- 16305029
TI  - [Form, modality and variety of music at the hospital setting].

PMID- 16305030
TI  - [Sound environment and music in neonatology].

PMID- 16305031
TI  - [Meeting space in neonatology].

PMID- 16305032
TI  - [The singer in my dreams].

PMID- 16305033
TI  - [Asthma and harmonica].

PMID- 16305034
TI  - [Music and adolescents].

PMID- 16305035
TI  - [The nutrition of the newborn en neonatal medicine].

PMID- 16305036
TI  - [Information about organ and tissue donation in colleges].

PMID- 16305037
TI  - [Analgesia in newborns and maternal breast feeding].

PMID- 16305038
TI  - PACS: small, medium or large.

PMID- 16305039
TI  - Tap, tap, tap to better patient documentation.

PMID- 16305040
TI  - Bringing evidence-based best practices into practice.

PMID- 16305041
TI  - Blueprint for a digital revolution.

PMID- 16305042
TI  - Healthy competition for data.

PMID- 16305043
TI  - Disease management and the national health information network: the emerging
      nexus.

PMID- 16305044
TI  - PACS/Imaging/Radiology HotList.

PMID- 16305045
TI  - Helping small hospitals think big.

PMID- 16305046
TI  - Pay-for-performance dominates changing contracting landscape.

PMID- 16305047
TI  - Lumetra QIO helps capitated groups redesign offices, implement EMR.
AB  - Capitated physician practices are far ahead of their fee-for-service cousins when
      it comes to using information technology to track patient care and finances. Read
      about how Lumetra and other quality improvement organizations are helping small
      capitated practices assess and install IT systems.

PMID- 16305048
TI  - Physicians, hospitals and health plans seek new risk-sharing arrangements.
AB  - Dollars paid to providers under capitation have declined the past four years, but
      new risk-sharing arrangements, pay-for-performance initiatives and a resurgence
      of Medicare Advantage members may turn the tide.

PMID- 16305049
TI  - Diabetes and cardiology: the common soil comes of age.

PMID- 16305051
TI  - Glycation, receptor-mediated cell activation and vascular complications of
      diabetes.

PMID- 16305050
TI  - RAGE and its ligands: a lasting memory in diabetic complications?
AB  - The complications of diabetes are myriad and represent a rising cause of
      morbidity and mortality, particularly in the Western world. The update of the
      Diabetes Control and Clinical Trials Group/Epidemiology of Diabetes Interventions
      and Complications Research Group (DCCT/EDIC) suggested that previous strict
      control of hyperglycaemia was associated with reduced carotid atherosclerosis
      compared to conventional treatment, even after levels of glycosylated haemoglobin
      between the two treatment groups became indistinguishable. These intriguing
      findings prompt the key question, why does the blood vessel 'remember'? This
      review focuses on the hypothesis that the ligand/RAGE axis contributes
      importantly to glycaemic 'memory'. Studies in rodent models of diabetes suggest
      that blockade or genetic modification of RAGE suppress diabetes-associated
      progression of atherosclerosis, exaggerated neointimal expansion consequent to
      acute arterial injury, and cardiac dysfunction. We propose that therapeutic RAGE
      blockade will intercept maladaptive diabetes-associated memory in the vessel wall
      and provide cardiovascular protection in diabetes.

PMID- 16305052
TI  - Acute coronary syndromes and diabetes mellitus.
AB  - Patients with diabetes mellitus who present with acute ST-segment elevation
      myocardial infarction or non-ST-segment elevation acute coronary syndromes have a
      higher risk of adverse outcomes than patients without diabetes, and appear to
      derive greater benefit from evidence-based therapies. However, patients with
      diabetes mellitus are less commonly treated with proven therapies, so renewed
      efforts are needed to improve the quality of care and outcomes for patients with
      diabetes mellitus who present with acute coronary syndromes.

PMID- 16305053
TI  - Treatment of CAD in patients with diabetes--what do we really know?

PMID- 16305054
TI  - Common polymorphisms in the glyoxalase-1 gene and their association with pro
      thrombotic factors.
AB  - Advanced glycation endproducts (AGEs) form at an accelerated rate in diabetes and
      contribute to the development of macrovascular disease. Their precursors are
      detoxified by the glyoxalase system. Perturbations of the glyoxalase-1 gene may
      alter AGEs' interactions and affect pro-thrombotic factors. We screened the
      glyoxalase-1 gene for mutations and measured pro-thrombotic markers in 537
      subjects from 89 healthy probands. Common single nucleotide polymorphisms (SNPs)
      were identified at positions -7 (C to T) and 20203 (C to A) from the translation
      start site. These SNPs were in Hardy-Weinberg equilibrium (CC=105, CA=266,
      AA=148; p>0.05; CC=126, CT=279, TT=114; p>0.05, respectively) and in linkage
      disequilibrium (D=27%, p<0.01), with mutant allele frequencies of 48% and 52%
      respectively. A significant association was found between SNPs at position 20203
      and PAI-1 antigen concentrations and -7 and factor XIII A2B2 complex (p=0.001 and
      p=0.042). After Bonferroni correction a significant association remained between
      the SNP at 20203 and PAI-1 concentrations (p=0.005), and after adjustment for
      pedigree the association accounted for 1.3% of its heritability (p=0.04). No
      significant associations were found for SNP -7 T to C and factor VII activity,
      tPa concentrations, fibrinogen concentrations or factor XIII concentrations and
      SNP 20203 C to A and factor VII concentrations, PAI-1 concentrations, tPa
      concentrations or fibrinogen concentrations. Common variants in the glyoxalase-1
      gene are associated with some pro-thrombotic factors, account for part of their
      heritability in healthy pedigrees and may alter susceptibility to macrovascular
      complications.

PMID- 16305055
TI  - Initial experience with GLP-1 treatment on metabolic control and myocardial
      function in patients with type 2 diabetes mellitus and heart failure.
AB  - Congestive heart failure (CHF) is a serious disease with a poor prognosis.
      Diabetes is an independent risk factor for CHF, probably in part due to
      disturbances in myocardial metabolism. Glucagon-like peptide-1 (GLP-1) causes
      glucose-dependent secretion of insulin, improving glycaemic control. In turn,
      this may improve myocardial metabolism and myocardial function. The aim of the
      present study was to assess the feasibility and safety of three days' infusion of
      recombinant GLP-1 in an open observational study in six patients with type 2
      diabetes and CHF. The study included assessment of myocardial function. There
      were no major complications of the infusion, and all patients completed the study
      protocol. Some improvement was observed in glycaemic state, and there was an
      insignificant trend towards improved myocardial function. It is concluded that
      GLP-1 deserves further evaluation in such patients.

PMID- 16305056
TI  - Pioglitazone plus a sulphonylurea or metformin is associated with increased
      lipoprotein particle size in patients with type 2 diabetes.
AB  - OBJECTIVE: To determine the effect of pioglitazone plus metformin or a
      sulphonylurea on lipoprotein particle size and subclass distribution in patients
      with type 2 diabetes. METHODS: Lipid profiles were determined for blood samples
      from patients participating in two randomised, double-blind, 24-week studies of
      pioglitazone 30 mg or 45 mg daily plus either metformin or a sulphonylurea.
      RESULTS: Samples from 177 patients were evaluated; 96 of these patients received
      a sulphonylurea, and 81 received metformin. Pioglitazone combination treatment
      produced significant increases from baseline for average and peak low-density
      lipoprotein (LDL) particle size at weeks 12 and 24 (p<0.0001 for each; range 0.29
      0.39 nm for average and 0.36-0.55 nm for peak particle size, respectively).
      Significant shifts in high-density lipoprotein (HDL) and LDL distribution showed
      an increase in large particles and a decrease in small particles. For
      pioglitazone plus metformin, significant increases in levels of apolipoprotein
      (Apo) Al, Apo Al/All-containing HDL, and lipoprotein(a) also were noted, whereas
      Apo B levels decreased. CONCLUSIONS: These observed changes are thought to affect
      the atherogenic profile positively. Therefore, pioglitazone combination treatment
      may lead to decreased cardiovascular risk in patients with type 2 diabetes.

PMID- 16305057
TI  - Fluctuations in glycaemia in clinical diabetes mellitus type 2 are not associated
      with carotid intima-media thickening.

PMID- 16305058
TI  - Whence and whither the fixed-dose combination?

PMID- 16305059
TI  - The application of proteomics to diabetes.
AB  - Poteomics is the investigation of all the proteins and their various
      modifications making up a system, be that a cell, tissue or organism. The
      techniques involved in proteomics allow the global screening of complex samples
      of proteins and provide qualitative and quantitative evidence of altered protein
      expression. This lends itself to the investigation of the molecular mechanisms
      underpinning disease processes and the effects of treatment. This review
      describes the main techniques of proteomics and how they have begun to be applied
      to diabetes research.

PMID- 16305060
TI  - Thiazolidinediones, peripheral oedema and congestive heart failure: what is the
      evidence?
AB  - Cardiovascular disease is the most common complication of type 2 diabetes
      mellitus (type 2 DM), accounting for approximately 80% of deaths. While
      atherosclerotic vascular disease accounts for much of the cardiovascular
      morbidity and mortality among diabetic patients, congestive heart failure (CHF)
      is another key complication associated with diabetes, with an incidence three to
      five times greater in diabetic patients than in those without diabetes. One of
      the most promising developments in the treatment of type 2 DM has been the
      introduction of the thiazolidinedione (TZD) class of drugs, which appear to have
      pleiotropic effects beyond glycaemic control. Enthusiasm has been tempered,
      however, by concerns for safety in patients with CHF, given reports of worsening
      heart failure symptoms and peripheral oedema. With the growing epidemic of type 2
      DM and the increasing use of TZDs, such concern has important therapeutic
      implications for a population of patients with a high prevalence of often
      subclinical systolic and diastolic dysfunction. This review provides an overview
      of the currently available data regarding the effects of TZDs on fluid retention
      and cardiac function. Particular emphasis is placed on the mechanisms of
      development of peripheral oedema and its significance in patients with impaired
      left ventricular function. TZDs are well known to cause an expansion in plasma
      volume; there has also been concern that TZDs may have direct toxic effects on
      the myocardium, leading to impaired cardiac function. Studies to date do not
      support this hypothesis and in fact there is growing evidence from animal models
      and human trials that treatment with TZDs actually improves cardiac function.
      There are also preclinical data to suggest TZDs may protect the myocardium in the
      setting of ischaemic insult or the toxic effects of myocardial lipid deposition.
      Ongoing clinical trials examining the use of these agents in patients at risk for
      heart failure will probably provide further insight into the aggregate
      cardiovascular effects of this promising class of medications.

PMID- 16305061
TI  - Cross-sectional evaluation of the Finnish Diabetes Risk Score: a tool to identify
      undetected type 2 diabetes, abnormal glucose tolerance and metabolic syndrome.
AB  - The aim of this study was to assess the performance of the Finnish Diabetes Risk
      Score as a screening tool for undetected type 2 diabetes (T2D), abnormal glucose
      tolerance (AGT) and metabolic syndrome in the general population. In a cross
      sectional, population-based survey, a total of 4,622 subjects aged 45-74 years
      were invited to a health examination that included an oral glucose tolerance
      test. Full data with risk score estimate and glucose tolerance status were
      available for 2,966 subjects without a prior history of diabetes. The risk score
      was associated with the presence of previously undiagnosed T2D, AGT, metabolic
      syndrome and cardiovascular risk factors. The area under the receiver operating
      curve for the prevalence of undiagnosed diabetes was 0.72 in men and 0.73 in
      women. The sensitivity using a cutoff risk score of 11 to identify undiagnosed
      diabetes was 66% in men and 70% in women; the corresponding false-positive rates
      were 31% and 39%, respectively. The area under the receiver operating curve for
      detecting the metabolic syndrome was 0.72 in men and 0.75 in women. The Finnish
      Diabetes Risk Score can be used as a self-administered test to screen subjects at
      high risk for T2D. It can also be used in the general population and clinical
      practice to identify undetected T2D, AGT and the metabolic syndrome.

PMID- 16305062
TI  - Contrasting clinical and cardiovascular risk status between early and later onset
      type 2 diabetes.
AB  - The prevalence of type 2 diabetes (T2DM) is increasing rapidly and the age of
      presentation is falling. These changes are likely to be linked to the current
      obesity epidemic. Our objective was to compare the characteristics of younger
      patients with T2DM (diagnosed at age < 40 years) with those of older patients
      (diagnosed at age 50-70 years). We identified 149 younger patients with T2DM,
      from our diabetes clinic database, and compared them with 217 older T2DM patients
      randomly identified from the same database. Younger patients with T2DM were more
      obese, more hypertriglyceridaemic, with lower high-density lipoprotein (HDL)
      cholesterol, higher total cholesterol/HDL ratio and worse initial and ongoing
      glycaemic control than older patients from the same clinic. Additional
      cardiovascular risk factors are associated with T2DM in the young. Treatment
      should be aimed at early modification of lifestyle and other forms of therapy to
      avoid long-term complications.

PMID- 16305063
TI  - Cells expressing the stem cell factor receptor, c-kit, contribute to
      neoangiogenesis in diabetes.
AB  - While neoangiogenesis in diabetes is of greatest clinical significance in the
      retina, the pathological formation of new blood vesselsalso develops in other
      vascular beds in diabetes, including the mesentery of the streptozotocin-induced
      diabetic rat. However, the contribution of bone marrow-derived cells to this
      process of vasculogenesis is unknown. In this study, male Sprague-Dawley rats
      were randomised to receive either streptozotocin or vehicle, and their mesenteric
      vasculature was examined after three weeks. Origins from bone marrow and
      endothelial cell differentiation were identified by immunolabelling for the stem
      cell factor receptor, c-kit and von Willebrand factor (vWF), respectively.
      Expression for the angiogenic chemokine, stromal derived factor-1 (SDF-1) was
      assessed by quantitative real-time polymerase chain reaction (PCR). At three
      weeks, rats with diabetes had a dramatic (190-fold) increase in lectin-labelled
      blood vessel profiles in the mesenteric bed (p < 0.0001) in association with a
      five-fold increase in SDF-1 mRNA (p < 0.01). Immunohistochemical studies
      identified abundant large, ovoid, lumen-forming, c-kit+ cells in the mesentery of
      diabetic, but not control, rats. Many of these c-kit+ cells also showed positive
      immunolabelling for vWF, consistent with endothelial differentiation. In
      conclusion, cells of bone marrow origin contribute to new vessel formation in the
      diabetic mesentery. This phenomenon may also apply to the neovascularisation that
      develops at clinically important sites such as in the retina.

PMID- 16305064
TI  - Platelet nitrate responsiveness in fasting and postprandial type 2 diabetes.
AB  - Vascular responsiveness to exogenous nitrates in type 2 diabetes (T2DM) is
      attenuated in brachial and coronary vessels. We determined platelet
      responsiveness to nitric oxide (NO) in T2DM and control subjects. We examined
      whether the postprandial (PP) state affected platelet sensitivity to NO donors in
      T2DM patients and the extent of correlation between this and measures of
      oxidative stress, compared to changes in endothelial function. Twelve T2DM
      subjects were studied fasting and four hours after a test meal and compared with
      15 healthy controls. We assessed the inhibitory effects of NO donors on adenosine
      5'-diphosphate (ADP)-induced platelet aggregation. Oxidative stress was assessed
      by lipid-derived free radicals, ex vivo by electron paramagnetic resonance
      spectroscopy and markers of lipid peroxidation. Endothelial function was assessed
      by flow-mediated vasodilatation (FMD) of the brachial artery. Results are
      expressed as (mean +/- SEM). Fasting platelet aggregation was increased in
      diabetics versus controls (14.86 +/- 1.1 Ohms vs. 10.76 +/- 1.1 Ohms, p < 0.05).
      Sodium nitroprusside (SNP) and glyceryl trinitrate (GTN) inhibited ADP-induced
      aggregation by 73.1 +/- 5.9% and 50.3 +/- 7.7% in healthy controls compared to
      15.4 +/- 7% and 19.5 +/- 8.2% in T2DM (p < 0.05). Fasting and postprandial
      inhibition of platelet aggregation with NO donors in T2DM was similar. T2DM
      patients had higher levels of oxidative stress in the fasting state and
      postprandially. There were no PP correlations with platelet NO resistance. In
      conclusion, there is platelet hyporesponsiveness to NO donors (SNP/GTN) in T2DM
      compared to controls, with increased ADP-induced platelet aggregation. Platelet
      abnormalities were associated with increased oxidative stress.

PMID- 16305065
TI  - Vascular research technique flow-mediated dilatation (FMD).

PMID- 16305066
TI  - Diabetes mellitus and vascular risk: continuing the quest for the elusive
      keystone.

PMID- 16305067
TI  - Impaired glucose tolerance and impaired fasting glucose--a review of diagnosis,
      clinical implications and management.
AB  - The diagnostic categories of impaired glucose tolerance (IGT) and impaired
      fasting glucose (IFG) were stablished in an effort to identify populations at
      risk for developing type 2 diabetes mellitus (T2DM). Both IGT and IFG are
      associated with increased risk of developing T2DM, but recent analyses found that
      the thresholds of risk vary among different populations and an even lower
      diagnostic threshold of IFG may be appropriate. IGT has been linked with an
      increased risk of cardiovascular events and some analyses have demonstrated an
      increased mortality risk compared with patients with normal glucose tolerance. In
      contrast, a continuum of increased risk of microvascular manifestations of T2DM
      has been demonstrated with IFG but an association of IFG with cardiovascular
      events has not been well established. Although both IGT and IFG are associated
      with resistance to insulin and increased insulin secretion, they do not identify
      the identical patient populations and are not equivalent in predicting
      development of T2DM or cardiovascular events. IFG and IGT have been associated
      with other features of insulin resistance, including dyslipidaemia, hypertension,
      abdominal obesity, microalbuminuria, endothelial dysfunction, and markers of
      inflammation and hypercoagulability, traits collectively referred to as the
      metabolic syndrome. Analyses of combinations of these components have also been
      associated with progression to T2DM, cardiovascular disease and increased
      mortality. The foundation of treatment for IGT, IFG, and the metabolic syndrome
      is lifestyle modification, including both dietary change and routine exercise. To
      date, several clinical trials have found that lifestyle modification is the most
      efficacious strategy to prevent progression to T2DM. Alternative treatments
      include pharmacotherapy with metformin or acarbose, both of which have been
      demonstrated to decrease the development of T2DM. Ongoing clinical trials are
      evaluating newer pharmacotherapies, including angiotensin converting enzyme
      inhibitors, angiotensin receptor antagonists, metglitinides and
      thiazolidinediones, to prevent both T2DM and cardiovascular events. In
      combination with lifestyle modification, these therapies offer hope for effective
      prevention of T2DM and its consequences in high-risk patients.

PMID- 16305068
TI  - Pathobiology and cell interactions of platelets in diabetes.
AB  - Diabetes is a well-recognised risk factor for atherosclerotic cardiovascular
      disease and in fact most diabetic patients die from vascular complications. The
      Diabetes Control and Complications Trial (DCCT) and the U.K. Prospective Diabetes
      Study (UKPDS) indicate a consistent relationship between hyperglycaemia and the
      incidence of chronic vascular complications in patients with diabetes. Platelets
      are essential for haemostasis, and abnormalities of platelet function may cause
      vascular disease in diabetes. Diabetic patients have hyperreactive platelets with
      exaggerated adhesion, aggregation and thrombin generation. In summary, the entire
      coagulation cascade is dysfunctional in diabetes. This review provides a
      comprehensive overview of the physiological role of platelets in maintaining
      haemostasis and of the pathophysiological processes that contribute to platelet
      dysfunction in diabetes and associated cardiovascular diseases, with special
      emphasis on proteomic approaches and leukocyte-platelet cross-talk.

PMID- 16305069
TI  - Tissue Doppler imaging for the detection and quantitation of myocardial
      dysfunction in patients with type 2 diabetes mellitus.
AB  - The prevalence of type 2 diabetes mellitus is rapidly increasing. Myocardial
      dysfunction may be a consequence of diabetic cardiomyopathy and it contributes to
      the poor prognosis of diabetic patients. AIMS: This study was designed to test
      whether tissue Doppler imaging might be a suitable tool for early detection of
      myocardial dysfunction in diabetic patients. METHODS: Forty-three diabetic
      patients and 33 non-diabetic controls, including age-matched subgroups without
      evidence of coronary artery disease (n=12), were recruited if they had normal LV
      function by standard 2-D echocardiography and no clinical signs of heart failure.
      They were investigated with tissue Doppler imaging at rest and during
      pharmacological stress with dipyridamole and/or dobutamine. Myocardial function
      was calculated as the mean value from six basal myocardial segments for peak
      velocity at systole (Vs), early diastole (Ve) and atrial contraction (Va).
      RESULTS: Compared to controls, diabetic patients had compromised Ve at rest (8.5
      +/- 1.7 vs. 9.6 +/- 1.9 cm/sec, p < 0.02), as did the subgroups without coronary
      artery disease (9.3 +/- 1.7 vs. 10.7 +/- 1.5 cm/sec, p < 0.05). Dobutamine stress
      resulted in lower Vs (10.7 +/- 2.7 vs. 13.6 +/- 3.4 cm/sec, p < 0.05) and Ve
      (10.0 +/- 2.1 vs. 13.1 +/- 3.8 cm/sec, p < 0.05) in the diabetic patients,
      demonstrating an impaired increase of Vs, Vd and Va (p < 0.05, p < 0.0003 and p <
      0.03, respectively). An inverse correlation was observed between Ve and age in
      both control and diabetic individuals. Thus, abnormal values were defined in
      relation to age. CONCLUSIONS: Diastolic and systolic myocardial dysfunction in
      patients with type 2 diabetes may be identified by quantitative tissue Doppler
      imaging before the onset of clinical signs of heart failure and before the
      appearance of traditional echocardiographic indices of systolic myocardial
      dysfunction.

PMID- 16305070
TI  - Metabolic syndrome-mediated inflammation following elective percutaneous coronary
      intervention.
AB  - There are few data concerning the relationship between diabetes mellitus, the
      metabolic syndrome and inflammation following elective percutaneous coronary
      intervention (PCI). The purpose of this study was to assess basal and peak levels
      of candidate cytokines in 40 patients undergoing elective PCI. Patients were
      categorised as having diabetes mellitus, the metabolic syndrome, or neither.
      Patients with the metabolic syndrome exhibited significantly greater levels of
      tumour necrosis factor-alpha over the study period, although this was unrelated
      to PCI. There was a trend for increased levels of interleukin-6 following PCI,
      primarily among patients with metabolic syndrome. Basal levels of monocyte
      chemoattractant protein-1 (MCP-1) were not different among study groups; however,
      the metabolic syndrome cohort had a trend towards increased circulating levels of
      MCP-1 after PCI. In this patient population, the metabolic syndrome correlates
      with a heightened inflammatory response following elective PCI.

PMID- 16305071
TI  - Effect of rosiglitazone treatment on circulating vascular and inflammatory
      markers in insulin-resistant subjects.
AB  - Thiazolidinedione (TZD) compounds enhance insulin sensitivity and attenuate
      inflammation. The effect of the TZD compound, rosiglitazone (RSG) on both actions
      was evaluated in two groups of insulin-resistant subjects with minimal elevations
      of fasting plasma glucose (PG) concentration: group A (n=15, PG < 7.0 mmol/L) and
      group B (n=14, PG 7.0-8.3 mmol/L). Insulin action, quantified by the insulin
      suppression test, improved after three months of treatment in both groups, and
      concentrations of C-reactive protein, plasminogen activator inhibitor-1 and
      Eselectin all fell. Significant decreases in L-selectin and P-selectin were
      confined to group B, and concentrations of interleukin-6, intercellular adhesion
      molecule-1 and vascular cellular adhesion molecule-1 did not fall in either
      group. Significant relationships were not discerned between enhanced insulin
      sensitivity and related variables and decreases in inflammatory/vascular markers,
      suggesting that RSG-induced changes in the latter variables in insulin-resistant
      individuals might be at least partly independent of the effects of the drug on
      insulin action.

PMID- 16305072
TI  - RAGE polymorphisms and the heritability of insulin resistance: the Leeds family
      study.
AB  - Activation of the receptor for advanced glycation end-products (RAGE) leads to a
      cascade of pro-inflammatory and pro-coagulant responses which are important in
      the pathogenesis of the vascular complications of diabetes mellitus. It is known
      that pro-inflammatory mechanisms underpin the development of type 2 diabetes. Our
      hypothesis is that RAGE may be involved in the evolution of insulin resistance in
      addition to mediating glucotoxic complications of diabetes mellitus. METHODS: To
      investigate the relationship between RAGE allelic variation and insulin
      resistance, the Gly82Ser variant and three promoter variants (-429, -374, 63 bp
      deletion) were studied in 480 subjects of known relationship from 89 families
      characterised for insulin resistance (using homeostasis model assessment [HOMA])
      and for atherothrombotic risk. Carriage of the -429 C allele was weakly
      associated with increased insulin resistance (p = 0.02) when pedigree analysis
      was performed using SOLAR software. RESULTS: Insulin resistance was estimated to
      have a heritability of 25.8% before the addition of covariates. Analysis of the
      relationship between RAGE and insulin resistance indicated that the -429
      polymorphism reduced the unexplained heritability of insulin resistance after
      adjusting for covariates (age, sex, body mass index) from 17.5% of the total
      variance to 15.6% of the total variance. CONCLUSIONS: These preliminary results
      indicate that the RAGE gene may affect the development of insulin resistance or
      be in linkage disequilibrium with a locus involved in this process.

PMID- 16305073
TI  - Osteomyelitis and septic arthritis in children.
AB  - Osteomyelitis is an infection in bone most frequently occurring in children. The
      current incidence is 1 in 5000. Septic arthritis is an infection of a synovial
      joint which may occur in all age groups in children but has a specific infantile
      form affecting the infant from birth to the first year of life. The majority of
      infections of bone or joint are caused by spread of bacteriae through the
      bloodstream or occasionally by entry of organisms through an open wound, by
      puncture or by extension of infection from adjacent tissue. The most common
      causative organism is Staphylococcus aureus but many other organisms may be
      responsible for a bone or joint infection. The treatment of both osteomyelitis
      and septic arthritis is based on antibiotic therapy in combination with surgical
      drainage if pus or infected tissue is present. Early diagnosis followed by
      adequate treatment gives good outcome. Inappropriate or delayed treatment may
      result in chronic osteomyelitis or irreversible joint destruction.

PMID- 16305074
TI  - First-time traumatic anterior dislocation of the shoulder in young adults: the
      position of the arm during immobilisation revisited.
AB  - In contrast to the surgical treatment of chronic shoulder instability, there are
      only scarce publications about the management after a first episode of anterior
      shoulder dislocation and how to prevent the evolution towards chronic
      instability. We present here a review of the literature on this subject.
      Particular attention is paid to recent studies about the position of the arm
      during immobilisation. According to recent views, it may be preferable to
      immobilise the arm in external rather than internal rotation, but this has to be
      confirmed by further clinical studies. The issue of early arthroscopic
      stabilisation after a first dislocation event in young athletic patients is also
      discussed.

PMID- 16305075
TI  - Surrounding soft tissue pressure during shoulder arthroscopy.
AB  - In 40 patients undergoing arthroscopic subacromial decompression, we monitored
      the soft tissue pressure in the paratracheal region and in the deltoid and
      supraspinatus muscles, looking for evidence of a potentially dangerous rise in
      pressure, especially in the paratracheal region. Statistical analysis was used to
      determine predictable variables of the time of reaching maximum pressure in and
      between the three regions. Deltoid pressure rose quickly during surgery, and did
      not drop to baseline levels at the end of surgery. Supraspinatus pressures showed
      a similar trend but with lower maximum levels of pressure rise. Five patients had
      an (unexpected) rise in paratracheal pressure, with an absolute maximum of 133.4
      mmHg in one. In only two patients, did "10 minutes post-op" paratracheal pressure
      levels not drop to baseline levels. No respiratory problems occurred during any
      procedure. There are no variables to predict a potentially dangerous rise in
      surrounding soft tissue pressure during shoulder arthroscopy. We recommend
      endotracheal intubation during shoulder arthroscopy.

PMID- 16305076
TI  - Ganglion cysts of the wrist : a prospective study of a simple outpatient
      management.
AB  - We present the results of a modified minimally invasive surgical technique in the
      management of ganglia of the wrist. Twenty six ganglia have been treated by this
      method. The patient satisfaction for the procedure was 92.3%. An average of 2
      days were lost off work consequent to the procedure. The use of this technique
      has resulted in a 77.9% mean resolution in size with 50% of the patients showing
      complete resolution. There were no recurrences noted in the 2 year follow-up.

PMID- 16305077
TI  - Relationship between dorsal ganglion cysts of the wrist and intraosseous ganglion
      cysts of the carpal bones.
AB  - Soft tissue ganglion cysts are the most common benign tumours of the wrist; their
      pathogenesis remains controversial. We prospectively screened the radiographic
      appearance of the wrists of 51 patients presenting to a single surgeon with
      dorsal wrist ganglions during a one-year period. Postero-anterior and lateral
      radiographs were systematically performed looking for possible associated
      intraosseous ganglion cysts. There were 51 dorsal soft tissue ganglion cysts in
      51 patients. We detected 29 associated intraosseous ganglia in 24 patients (47%):
      16 ganglia in the lunate bone (55%), 5 in the capitate bone, 7 in the scaphoid
      and 1 in the trapezoid. Mean size of the intraosseous ganglia was 3 mm (range, 2
      to 5 mm). This high prevalence of intraosseous ganglia in association with soft
      tissue ganglia has to our knowledge never been reported previously. A common
      aetiology for these two types of ganglion cysts may explain this high association
      rate.

PMID- 16305078
TI  - Do pain referral patterns determine patient outcome after total hip arthroplasty?
AB  - Quality of life outcome and patient satisfaction after total hip arthroplasty are
      complex phenomena and many confounding determinants have been identified.
      Degenerative disease of the hip joint may present with variable patterns of pain
      referral in the lower limb. However the effect of varied preoperative pain
      referral patterns on patient outcome and satisfaction after total hip
      arthroplasty has not previously been examined. From 2000 to 2003, 236 eligible
      patients scheduled to undergo primary total hip arthroplasty were prospectively
      enrolled. The principal pain referral pattern (as hip, thigh or knee) was
      identified in all patients. Health related quality of life (HRQOL) was examined
      using the Harris Hip score (HHS), the Western Ontario McMaster Universities
      Osteoarthritis Index (WOMAC) and the 36-Item Short-Form Health Survey (SF-36) pre
      operatively, 1 year and 2 years postoperatively and with the HHS at 3 months
      postoperatively. All patients were followed up for a minimum of 2 years. The
      frequency of the pain referral distributions were; hip pain 41%, knee pain 32%
      and thigh pain 27%. Patients in all groups were comparable preoperatively with
      respect to age, HHS, and both mean and domain specific WOMAC and SF-36 scores.
      The mean duration of symptoms was significantly greater in patients with knee
      pain when compared to the remaining two pain patterns. All patients demonstrated
      improvements in HHS, SF-36 and WOMAC scores after surgery. At all times
      postoperatively there were significant differences in mean HHS and mean and
      domain specific WOMAC and SF-36 scores between patients with hip or thigh pain
      and those with knee pain (p < 0.001). While notable, differences between hip and
      thigh pain were not as consistent however. Based on these findings, it appears
      that pre-operative pain referral patterns of hip arthritis are among the
      determinant factors for patient outcome and satisfaction after total hip
      arthroplasty, as measured using validated HRQOL scoring systems.

PMID- 16305079
TI  - Primary hip arthroplasty through a limited posterior trochanteric osteotomy.
AB  - This study evaluates primary hip replacement performed using a modified posterior
      approach through a limited posterior trochanteric osteotomy bone block that
      includes the insertions of the posterior capsule and short external rotators--as
      this may enhance secure reattachment of the posterior soft-tissue envelope and
      protect against postoperative instability. Sixty-eight consecutive primary hip
      replacements performed through a posterior trochanteric osteotomy were
      prospectively followed. Two were lost to follow-up before a minimum of 2 years
      after the arthroplasty; the remaining 66 hips were followed for a mean of 10
      years (range: 2 to 15). The median Harris hip score improved from 43 to 84 points
      (p < 0.0001). Radiographic union of the osteotomy was confirmed in 64 hips (94%).
      Two episodes of early dislocation occurred 5 days and 8 months postoperatively;
      both were successfully managed nonoperatively without continuing instability.
      There were no cases of late instability. Posterior approach to the hip joint
      through a posterior trochanteric osteotomy is associated with high union rates
      and a low rate of late instability after hip replacement.

PMID- 16305080
TI  - Assessment of early migration and clinical evaluation of a cemented femoral stem.
AB  - A 2-year follow-up study was conducted on 46 patients to assess Harris Hip Scores
      (HHS) and early distal migration of the femoral stem after total hip arthroplasty
      using a fully cemented femoral stem. The mean age was 73.4 years. The Fullfix
      stem (Mathys A.G., Bettlach, Switzerland) is characterised by a mat polished
      surface and a flange aimed to compress the cement during the insertion process.
      Early distal migration was determined in 36 patients using the computer assisted
      EBRA-FCA method (Einzel-Bild-Roentgen-Analyse femoral component analysis). At 2
      years, subsidence reached a mean value of 0.44 mm (95% CI: 0.19, 0.70),
      whereafter the stem appeared stable, i.e. distal migration reached a plateau.
      Females showed significantly higher migration than males (p < 0.01). EBRA-FCA
      proved to be an accurate method to measure early migration, with a standard
      deviation below 1 mm (0.56 mm in the interval 1-2 years). Harris Hip Scores (HHS)
      at 2 years follow-up averaged 89.6 (95% CI: 79.5, 99.8). As expected considering
      the small extent of migration, there was no correlation between subsidence and
      HHS (p = 0.5).

PMID- 16305081
TI  - Intraoperative arthrometry in anterior cruciate ligament reconstruction.
AB  - Arthrometry has an established role in the measurement of knee laxity in anterior
      cruciate ligament injury and following reconstruction. The role of routine
      intraoperative arthrometry in anterior cruciate ligament reconstruction is poorly
      defined, and this study was designed to test the hypothesis that intraoperative
      arthrometry provides an objective method of documenting successful knee
      stabilisation following anterior cruciate ligament reconstruction. A consecutive
      cohort of 100 patients with unilateral isolated anterior cruciate ligament
      disruption were prospectively evaluated using a Rolimeter arthrometer. A maximal
      manual force method was utilised by a single examiner. This allowed for side-to
      side comparisons with the uninjured contralateral knee. Analysis of tibial
      translation was recorded preoperatively with patients both awake and asleep,
      intraoperatively following anterior cruciate ligament reconstruction, and
      postoperatively at 2 weeks and 3 months. Statistical analysis was performed using
      Spearman's correlation coefficients. Intraoperative arthrometry of anterior
      cruciate ligament reconstructed knees revealed statistically significant
      correlation with measurements of uninjured knees (p < 0.0001). These findings
      were reproducible at 2 weeks (p < 0.0001) and at 3 months (p = 0.0002). Based on
      our findings, we conclude that intraoperative arthrometry can be simple and
      provide reproducible results. It is a useful method of immediately and
      objectively documenting successful anterior cruciate ligament reconstruction.

PMID- 16305082
TI  - Pulsed electromagnetic stimulation of regenerate bone in lengthening procedures.
AB  - Distraction osteogenesis for limb lengthening represents the treatment of choice
      in patients with small stature or limb length discrepancies. Bone lengthening and
      callus formation requires a long therapy. Pulsed electromagnetic fields (PEMF)
      are normally used to enhance osteogenesis in patients with non-unions. In this
      study we investigated whether pulsed electromagnetic fields could be used
      effectively to encourage callus formation and maturation during limb lengthening
      procedures. Thirty patients underwent bilateral bone lengthening of the humerus,
      femur or tibia. At day 10 after surgery, PEMF stimulation was started on one
      side, for 8 hours/day. Stimulated distraction sites exhibited earlier callus
      formation and progression, and a higher callus density compared to non-stimulated
      sites. External fixation could be removed on average one month earlier in PEMF
      stimulated bones. Our results show that the use of pulsed electromagnetic fields
      stimulation during limb lengthening allows shortening the time of use of the
      external fixation.

PMID- 16305083
TI  - Prophylactic surgical correction of Crawford's type II anterolateral bowing of
      the tibia using Ilizarov's method.
AB  - The treatment of anterolateral bowing with an intact tibia is directed toward
      prevention of the fracture and subsequent pseudoarthrosis. Patients with
      anterolateral bowing of the tibia are usually treated with an ankle-foot orthosis
      until the deformity is improved. There is no documentation that an orthosis can
      prevent the fracture or correct the deformity, and if the deformity is not
      corrected, it will result in different mechanical problems. In this study, 6 legs
      in 6 patients with anterolateral bowing of the tibia with a narrow sclerotic
      medullary canal (Crawford type II) were treated using Ilizarov's method. The
      average age was 6.8 years. All patients underwent correction of the anterolateral
      bowing by excision of the affected part. If the gap was less than 4 cm, acute
      shortening followed by bone lengthening was done. If the gap was more than 4 cm,
      bone transport was preferred. The mean duration of follow-up was 3.2 years. The
      anterolateral bowing was corrected in all patients. Complications such as pin
      track infection, premature consolidation and delayed union at the docking site
      were encountered. We believe that Ilizarov's method offers a more efficient
      solution for this type of deformity than prophylactic orthotic treatment or
      prophylactic bypass bone graft.

PMID- 16305084
TI  - Management of comminuted closed tibial plafond fractures using circular external
      fixators.
AB  - Various types of external fixators have been used to treat Ruedi and Allgower
      Type III pilon fractures, as serious complications can occur using conventional
      treatment principles. However, insufficient reduction and loss of reduction are
      two of the main disadvantages of external fixator treatments. We conducted a
      retrospective review of 14 patients with severe highly comminuted closed
      fractures of the distal tibia (Ruedi type III) treated using cross-ankle external
      fixators. Five patients underwent closed reduction, while the others required
      open reduction using minimal incision techniques. The reduction score, reduction
      loss, early and late complications, and ankle symptoms and functions were
      evaluated. The patients were followed for an average of 48 months (range: 31 to
      84); superficial wound infection developed in one case and minimal angular
      deformity in another. In ten cases, the reduction of the articular surface was
      anatomical; in the other four cases, it was non-anatomical. Except for one case
      which developed an angular deformity, no loss of reduction was observed. On
      radiological control, only one case did not display osteoarthrosis; in the other
      13 cases, osteoarthrosis was diagnosed at different levels. The most important
      disadvantage of this technique is retarded joint movement. Nevertheless, for such
      fractures, we consider cross-ankle circular external fixators as an alternative
      treatment method because it combines the advantage of a minimal risk of deep
      infections with better stabilisation of the limb, while providing early
      mobilisation.

PMID- 16305085
TI  - Ultrasound and colour Doppler sonography in acute osteomyelitis in children.
AB  - Early diagnosis of osteomyelitis is of paramount importance to avoid irreversible
      sequelae. This often requires a multimodal approach. The purpose of the present
      study was primarily to evaluate how ultrasound might be useful in early diagnosis
      of osteomyelitis in the paediatric age group. The evolution of ultrasound
      findings with progression and resolution of disease was also analysed. In this
      prospective study, 55 children with osteomyelitis of limbs were subjected to
      sonographic examination including colour Doppler study. The sonographic machine
      used was a LOGIC-500, using a linear multifrequency transducer (7-9 MHz).
      Ultrasound guided aspiration was performed in all cases showing sub-periosteal
      accumulation of fluid, and the aspirate was sent for culture and sensitivity
      report. Surgical drainage was undertaken in all patients in which a sub
      periosteal abscess was demonstrated. Anechoic fluid accumulation contiguous with
      bone was highly suggestive of osteomyelitis, whereas presence of soft tissue
      between the bone and the fluid suggested a non-osseous origin of the fluid. Sub
      periosteal accumulation of fluid was seen in 42 cases (76.3%). A subperiosteal
      abscess with periosteal reaction was demonstrated in 35 children (63.63%). Colour
      Doppler study revealed increased vascular flow within or around the affected
      periosteum in all cases. Concurrent involvement of a joint was noted in 13 cases.
      Ultrasound is a rapid, cheap, easily available, non-ionising and reasonably
      accurate diagnostic modality. It also helps in localising the lesion for
      diagnostic aspiration. Serial ultrasound and technical innovations such as colour
      Doppler sonography further help in monitoring the progression and resolution of
      the disease.

PMID- 16305086
TI  - Vertebral body reconstruction with injectable hydroxyapatite cement for the
      management of unstable thoracolumbar burst fractures: a preliminary report.
AB  - The aim of this prospective study was to evaluate the efficacy of an injectable
      hydroxyapatite cement in combination with long posterior transpedicular
      instrumentation, without fusion, for the treatment of unstable thoracolumbar
      burst fractures. Ten patients with this type of fracture were treated in the
      period 1999-2000 with bisegmental posterior transpedicular stabilisation above
      and below the fracture site, indirect reduction of the fracture, and
      transpedicular injection of hydroxyapatite cement into the fractured vertebral
      body. Postoperatively the mean Cobb kyphotic deformity angle (CKDA) and vertebral
      compression index (VCI) were statistically improved (p < 0.001). Both variables
      deteriorated slightly between surgery and follow-up after +/- 39 months; this was
      statistically not significant for the CKDA (p > 0.05), but significant for the
      VCI (p < 0.001). These data suggest that hydroxyapatite cement can be a reliable
      way to reinforce the fractured vertebral body in the thoracolumbar region.

PMID- 16305087
TI  - Anterior cervical interbody fusion with radiolucent carbon fiber cages: clinical
      and radiological results.
AB  - The authors retrospectively evaluated 30 patients with an anterior cervical
      interbody fusion for cervical spondylosis or disc herniation. Open box carbon
      fiber cages were used at 45 levels. The visual analogue scales (VAS),
      respectively for neck and for arm pain, and the neck disability index (NDI)
      improved significantly (p < 0.001). Fusion occurred in 87% of the operated
      levels. Subsidence of the cages into the endplates was observed in 49% of the
      operated levels, which increased to 54% when more levels were fused. No
      correlation between subsidence of the cage and clinical outcome or radiographic
      fusion was established. The authors conclude that cervical discectomy and
      interbody fusion using an open box carbon fiber cage is a satisfactory treatment
      option for degenerative cervical disease causing neck pain and radiculopathy,
      despite the relatively high percentage of subsidence of this cage.

PMID- 16305088
TI  - A simple K-wire cap.
AB  - The authors describe a simple technique to cap sticking K-wires using plastic
      syringes readily available in the hospitals, that has not been described before.

PMID- 16305089
TI  - Fracture of the scapular spine in a patient with a Delta III prosthesis.
AB  - Isolated scapular spine fractures are rare and are usually associated with other
      injuries. We describe a patient with a Delta III shoulder replacement who
      sustained a displaced ipsilateral fracture of the scapular spine after a fall.
      Internal fixation of the fracture resulted in excellent pain relief and
      restoration of the pre-existing shoulder mobility.

PMID- 16305090
TI  - Isolated fracture of the coronoid process.
AB  - Approximately 2% to 15% of the patients with dislocated elbows are thought to
      present a fracture of the coronoid process of the ulna, but such a fracture does
      not often present in isolation. Its exact incidence is difficult to ascertain
      given the lack of studies on the subject. One case is presented of an isolated
      fracture of the coronoid process and it is placed in the context of the existing
      literature.

PMID- 16305091
TI  - Tenosynovial haemangioma of the finger.
AB  - Haemangiomas developing in the hand in relation to tendon and the tenosynovium
      (tendon sheath) are very rare. To our knowledge only three cases have been
      described arising in relation to the tenosynovium of the tendons of the hand,
      only one of which showed infiltration of the underlying tendon. We report the
      case of a 16-year-old right hand dominant student who presented to her family
      doctor with a swelling on her left little finger. An MRI scan was arranged which
      confirmed a soft tissue lesion between the flexor tendons and the proximal
      phalanx of the left little finger, with appearance similar to giant cell tumour
      of the tendon sheath. Surgical exploration demonstrated a dark red fleshy tumour
      that appeared to infiltrate the flexor digitorum sub-limis tendon, and extend
      around either side of the proximal phalanx. For complete excision of the lesion
      the infiltrated sublimis tendon and a part of the A2 pulley were sacrificed.
      There was no resultant bow-stringing of the profundus tendon. Histologically the
      tenosynovium was expanded by a vascular lesion consisting of dilated, thin-walled
      vascular channels within fibrous tissue; the appearances were consistent with
      those of a synovial haemangioma of the flexor tendons. Our case illustrates the
      pitfalls in diagnosis and the invasive potential of a synovial haemangioma. A
      complete surgical excision is critical to prevent recurrence.

PMID- 16305092
TI  - Management of an unusual intra- and extra-capsular subcapital femoral neck
      fracture.
AB  - Femoral neck fractures are common in the elderly after low-energy falls. They are
      broadly grouped into either intracapsular or extracapsular fractures. We report
      an unusual subcapital femoral neck intra-extracapsular fracture and discuss the
      management of such a case with its inherent problems.

PMID- 16305093
TI  - Rare presentation of osteoarticular tuberculosis.
AB  - The varied clinical presentation of osteoarticular tuberculosis makes the
      diagnosis an enigma. This report underlines the fact that osteoarticular
      tuberculosis can present in the most atypical pattern. It also emphasises the
      need for a high index of clinical suspicion and the low threshold for tissue
      biopsy for establishing the diagnosis.

PMID- 16305094
TI  - Unusual mechanism of Chance fracture in an adult.
AB  - Flexion-distraction injuries of the upper lumbar spine typically occur in case of
      a head-on motor vehicle collision, while wearing a lap seat belt without shoulder
      strap. According to Smith and Kaufer the axis of flexion is situated at the point
      of contact of the belt with the abdominal wall. This results in a horizontal
      separation of the anterior, middle and posterior columns. The lesion is called a
      Chance fracture when it involves primarily bone, rather than ligaments. However,
      a Chance fracture can happen in unbelted persons: the present case concerns a 30
      year-old man who fell from a height.

PMID- 16305096
TI  - [What is your mentor like?].

PMID- 16305095
TI  - [Pro and con].

PMID- 16305097
TI  - [Review of thirty patients with bone chondroblastoma].
AB  - BACKGROUND/AIM: To analyse the results of the treatment of the patients with the
      diagnosis of chondroblastoma, to confirm the possible malignancy and to recommend
      the best and the safest method of the treatment. METHODS: We reviewed the cases
      of 30 patients with chondroblastoma who were treated between 1975 and 2004. Data
      were obtained using complete medical documentation, physical examinations,
      radiographic findings, and the available additional diagnostic procedures.
      RESULTS: We found that the proximal part of the tibia, proximal part of the
      humerus, and distal part of the femur were the most common sites of the tumor in
      63% of the cases. The higher prevalence of chondroblastoma in male patients was
      found, especially in the second decade of life. The patients were treated with
      different surgical procedures after histologically confirmed chondroblastoma. In
      1 of the patients, radiation therapy was performed because the lesion recurred,
      after which the malignant transformation of chondroblastoma occured. We found two
      more malignant chondroblastomas, one of which had been diagnosed as a primary
      tumor. Seven patients had a local recurrence, one of them had a second recurrence
      and the malignant transformation of chondroblastoma. The only solution was a
      below-knee amputation. CONCLUSION: Chondroblastoma of bone is a rare lesion with
      the high local recurrence rate. We emphasized the need for an adequate and rapid
      diagnosis, including histological verification. The treatment was strictly
      surgical. The basic goal of the treatment was to avoid tumor penetration into
      articular cavity and/or local soft tissues. Malignant chondroblastoma of bone
      should be treated with radical surgical resection, avoiding any adjuvant therapy.

PMID- 16305098
TI  - [Risk factors for the development of pneumonia in acute psychotropic drugs
      poisoning].
AB  - BACKGROUND/AIM: Pneumonia is the most frequent complication in acute psychotropic
      drugs poisoning, which results in substantial morbidity and mortality, but which
      also increases the costs of treatment. Risk factors for pneumonia are numerous:
      age, sex, place of the appearance of pneumonia, severity of underlying disease,
      airway instrumentation (intubation, reintubation, etc). The incidence of
      pneumonia varies in poisoning caused by the various groups of drugs. The aim of
      this study was to determine the incidence and risk factors for pneumonia in the
      patients with acute psychotropic drugs poisoning. METHODS: A group of 782
      patients, out of which 614 (78.5%) with psychotropic and 168 (21.5%)
      nonpsychotropic drug poisoning were analyzed prospectively during a two-year
      period. The diagnosis of pneumonia was made according to: clinical presentation,
      new and persistent pulmonary infiltrates on chest radiography, positive
      nonspecific parameters of inflammation, and the microbiological confirmation of
      causative microorganisms. To analyze predisposing risk factors for pneumonia, the
      following variables were recorded: sex, age, underlying diseases, endotracheal
      intubation, coma, severity of poisoning with different drugs, histamine H2
      blockers, corticosteroids, mechanical ventilation, central venous catheter. The
      univariate analysis for pneumonia risk factors in all patients, and for each
      group separately was done. The multivariate analysis was performed using the
      logistic regression technique. RESULTS: Pneumonia was found in 94 (12.02%) of the
      patients, 86 of which (91.5%) in psychotropic and 8 (8.5%) in nonpsychotropic
      drug poisoning. In the psychotropic drug group, pneumonia was the most frequent
      in antidepressant (47%), and the rarest in benzodiazepine poisoning (3.8%). A
      statistically significant incidence of pneumonia was found in the patients with
      acute antidpressant poisoning (p < 0.001). Univariate analysis showed statistical
      significance for the following parameters: sex (p < 0.05), chronic alcohol intake
      (p < 0.05), underlying diseases (p < 0.01), central venous catheter (p < 0.05)
      vasopressors (p < 0.05), coma (p < 0.001), H2 blockers (p < 0.001) and
      corticosteroids (p < 0.001). The multivariate analysis retained endotracheal
      intubation and antidepressant drug poisoning as an independent risk factor for
      pneumonia. CONCLUSION: Using univariate and multivariate analysis, risk factors
      for developing pneumonia were disclosed. Some of these factors may be modified by
      simple medical procedures, thus the incidence and mortality rate of pneumonia in
      drug poisoning might be substantially reduced.

PMID- 16305099
TI  - [Comparative analysis of the efficacy and biocompatibility of various methods of
      dialysis].
AB  - BACKGROUND/AIM: The efficacy and biocompatibility of hemodialysis have a
      singnificant impact on dialysis patient morbidity and mortality rate. The aim of
      our study was to compare the efficacy and biocompatibility of different
      hemodialysis modalities in our patients. METHODS: A total of 55 patients were
      included in the study, and on the basis of dialysis modality, they were divided
      in four groups: group I--post-dilution on-line hemodiafiltration (n=15), group II
      -bicarbonate high-flux polysulphone hemodialysis (n=15), group III--bicarbonate
      low-flux polysulphone hemodialysis (n=15), and groupe IV--bicarbonate cuprophane
      hemodialysis (n=10). The efficacy was evaluated on the basis of urea reduction
      rate (URR), urea Kt/V index and serum beta2-microglobuline reduction rate, and
      the biocompatibility was evaluated on the basis of the leukocyte count fall
      during the first fiftheen minutes of dialysis session, and of the serum C
      reactive protein (CRP) level. RESULTS: The highest mean URR was achieved in the
      group I (70.53 +/- 6.49%), and it was significantly higher in comparison with the
      average URR in the group IV (54.8 +/- 6.35%) (p = 0.001). The average value of
      urea Kt/V index in the group I (1.48 +/- 0.22) was significantly higher in
      comparison with the average value in the group II 1.30 +/- 0.22 (p < 0.05), group
      III (1.05 +/- 0.22), and group IV (0.98 + 0.22) (p = 0.001). Serum beta2
      microglobuline reduction rate was 68.93 +/- 8.25% in the group I, and 58.86 +/-
      7.98% in the groupe II (p = 0.01). During the first 15 minutes of hemodialysis
      the leukocyte number was decreased by 12.57 +/- 9.35% in the group 1, 13.61 +/-
      9.64% in the group 11, 18.3 +/- 13.24 in the group III and 62.3 +/- 15.4 in the
      group IV, on average. The mean serum level of CRP was 9.4 +/- 6.47 mg/l in the
      group IV, and less than 3.5 mg/l in the group I of the patients (p = 0.001).
      CONCLUSION: Postdilution on-line hemodiafiltration in comparison with standard
      hemodialysis provided the more effective elimination of small and middle uremic
      toxins molecules and a significantly higher degree of biocompatibility. The
      patients treated with standard hemodialysis frequently do not achieve the minimal
      value of urea Kt/V index prescribed by National Kidney Foundation-Dialysis
      Outcomes Quality Inatiatives standards. These patients also have significantly
      higher serum CRP values which suggest the state of chronic microinflammation.

PMID- 16305100
TI  - [Percutaneous transluminal coronary angioplasty in the right ventricle myocardial
      infarction treatment].
AB  - BACKGROUND/AIM: To present the results of percutaneous transluminal coronary
      angioplasty (PTCA) in the treatment of the patients with acute right ventricle
      myocardial infarction (ARVMI), with adjuvant analyses of the obtained results in
      the period of five years (2000-2004). METHODS: Thrombolytic therapy and the
      primary percutaneous transluminal coronary angioplasty (PPTCA) was applied within
      the first 6 hours from the onset of anginous disorders, and rescue PTCA in the
      period from 6-24 hours from the onset of ARVMI. Results. A total number of 1175
      patients, both sexes, 763 (64.8%) males and 412 females (35.2%), mean age 58.4 +/
      7.8 years, were treated for acute myocardial infarction (AIM) of different
      localization in the period of five years (2000-2004). Anterior infarction was
      found in 645 (54.8%) of the patients, and inferoposterior infarction (IPI) was
      localized in 530 patients (45.2%) patients of which in 134 (25.2%) AIMDK was
      proven. Out of 134 patients with proven acute myocardial of the right ventricle
      AIMDK, 53 (39.5%) got thrombolytic therapy, 64 patients (47.7%) were treated with
      the conservative heparin therapy, whereas in 17 patients (12.8%), primary
      percutaneous coronary angioplasty (PPTCA) was done. Delayed or rescue PTCA was
      done in 22 (18.8%) patients, in 8 (36.3%) from the group which got thrombolytic
      therapy, and in 14 (63.7%) treated with the heparin therapy. Out of the total
      number of 22 patients who got heparin or thrombolytic therapy combined with
      rescue PTCA, in 7 patients (31.8%) the complete clinical and angiographic effect
      of thrombolysis with AIM was achieved only by using a balloon. Baloon dilatation
      with the implantantion of intracoronary stent was performed in another 11
      patients (50%), while 2 (9.1%) were sent to revascularization of the myocard due
      to diffusion changes in each of the 3 blood vessels, and 2 patients (9.1%) died.
      Of the patients, 17 (12.6%) had PPTCA with the implantation of intracoronary
      stent with the additional direct inhibitor of the platelet membrane glycoproteins
      IIb/IIIa (abciximab). All the patients treated in this way survived. They had no
      side effects nor serious complications. Their clinical recovery was satisfactory.
      In the first three weeks of the intrahospital period in the group of 45 patients
      (33.5%) with AIMDK, who got only thrombolytic therapy, 7 patients (15.5%) died,
      whereas in the group of 50 patients (37.3%) treated only with heparin, 13 (26%)
      died. In the group of 22 patients (18.8%) treated with the combined therapy with
      rescue PTCA and heparin or thrombolytic therapy, 2 patients (9.1%) died. In the
      group of 84 patients (62.6%) with AIMDK, who were treated with thrombolytic
      therapy with primary or rescue PTCA, 9 (10.7%) died. In the AIMDK group of 134
      patients, 22 patients (16.4%) died in the period of 1 month of the hospital
      treatment, whereas in the second group of 396 patients with IPI, but without IDK,
      36 (9.1%) died (chi2 = 4.789; p < 0.001). Out of the total number of 1175
      patients with AIM in the five-year period of the intrahospital treatment, 145
      patients (12.3%) died. In the group of patients with IPI, 58 patients out of 530
      (10.9%) died, whereas 87 patients out of 645 (13.4%) with anterior infarction
      died, (chi2 = 0.567; p < 0.452). CONCLUSION: The combination of thrombolytic
      therapy and PTCA shown in the obtained results completely justified this kind of
      treatment, and offered the patients with AIMDK a greater chance to surve than
      they had before.

PMID- 16305101
TI  - [Possibility of the use of serological method for the determination of
      immunoglobuline A antibody against early antigene of Epstein-Barr virus as a
      marker in the diagnosis of nasopharyngeal tumors].
AB  - BACKGROUND/AIM: According to the data from immunological, biological and
      molecular researches, there is a close association between the undifferentiated
      carcinoma of nasopharyngeal type (UCNT) and Epstein-Barr virus (EBV). To use IgA
      EA antibody as a serological marker in our patients with nasopharyngeal carcinoma
      from a clinical viewpoint. METHODS: 91 patients were followed in the period from
      1989-1998. In 11 of the patients the antibody titre serum for the early antigen
      of EBV virus were determinated before the treatement, and in 24 of the patients 3
      years after the treatement. There were three control groups of patients: 20
      voluntary blood donors, 26 patients with squamocellular laryngeal carcinoma, and
      10 patients with squamocellular nasopharyngeal carcinoma. RESULTS: In the group
      of 11 patients with UCNT before the treatment, the value of anti-EA IgA titre was
      31.09, and in the patients after the treatement anti-EA IgA antiody titre was
      14.56. In the control groups of patients the results were: in the blood donors
      5.00; in the group with the diagnosis of squamocellular laryngeal carcinoma, the
      titre was 5.00; in the patients with squamocellular nosopharyngeal carcinoma, the
      titre anti-EA IgA was 5.36. CONCLUSION: These results were statisticly highly
      significant (p < 0.01). Our research clearly showed that anti-EA IgA EBV marker
      could be useful in diagnosing, differential diagnosing and prognosing as well.

PMID- 16305102
TI  - [Renal scintigraphy in children with urinary tract infections].
AB  - BACKGROUND/AIM: To determine the incidence of abnormal Technetium Tc 99m
      Dimercaptosuccinic Acid (Tc99m DMSA) renal scintigraphy findings in the children
      with urinary tract infection (UTI), and to evaluate the difference between the
      children with UTI and vesico-ureteral reflux (VUR), and the children with UTI
      without VUR. METHODS: Tc99m DMSA renal scintigraphy was performed in 170 children
      with UTI, mean age 7.07 years (1 month to 14 years, 137 were girls and 33 were
      boys). In 88 of the children, VUR was proved by micturating cystouretherography
      (MCU), while in 82 VUR could not be detected by MCU. VUR was graded in accordance
      with MCU recommended by the intemational study of VUR. In 13 of the children the
      grade of VUR was grade I, in 30 was grade II, in 23 grade III, in 17 grade IV,
      while the grade V was in 5 of the children. Findings of Tc99m DMSA renal
      scintigraphy were classified as: 1--normal, 2--probably normal, 3--equivocal, 4-
      probably abnormal, and 5--abnormal. The degree of the significance of the
      difference of the findings was estimated using chi2, taking p < 0.01 as the limit
      of statistical significance. RESULTS: Of the total number of 170 studied
      children, the abnormal findings were detected in 30% (51/170), normal findings in
      62% (106/170), and equivocal in 8% (13/170). In the children with UTI and VUR,
      the incidence of abnormal findings was 49% (43/88), of normal 43% (38/88), and of
      equivocal findings 8% (7/88). All the children with VUR grade V had the abnormal
      findings (the incidence of the abnormal findings was 100%). In the children with
      VUR grade IV, the abnormal findings were 71%. In the children with VUR grade I,
      77% of the findings were normal, in the children with VUR grade II 53% of the
      findings were normal and in the children with VUR grade III, 30% otfthe findings
      of renal scintigraphy were normal. In the children with UTI without VUR, the
      incidence of abnormal findings was 10% (8/82), of normal findings 83% (68/82),
      and of equivocal findings 7% (6/82). The incidence of abnormal findings was
      significantly higher in the children with UTI and VUR than in those with UTI
      without VUR (p < 0.01). Also, the incidence of the abnormal findings was higher
      in the children with VUR grades IV and V than in the children with VUR grade I (p
      < 0.01). CONCLUSION: DMSA renal scintigraphy in the children with ITU revealed
      the abnormal findings in 30% of the cases. The incidence of the abnormallfindings
      was signficantly higher when VUR was present, as well as if the grade of VUR was
      higher. Our results confirmed that Tc99m DMSA renal scintigraphy was a very
      important technique in the evaluation of the children with ITU.

PMID- 16305103
TI  - [Nitric oxide, neurodegeneration, and Parkinson's disease].

PMID- 16305104
TI  - Clinical pharmacology in health care service.

PMID- 16305105
TI  - [Solid-pseudopapillary tumors of the pancreas].
AB  - BACKGROUND: Solid-pseudopapillary tumors of the pancreas (SPT) is a very rare
      lesion. We presented the clinical and pathological characteristics of this tumor
      and reviewed the literature. CASE REPORT: We analysed the treatment of the two
      female patients, aged 21 and 37 years, with this tumor. The first female patient
      had the tumor withont involvement of the surrounding organs. The second female
      patient had the tumor with a high grade of malignancy which invaded blood
      vessels. We performed in both patients splenohemipancreatectomy, and then we
      reported the pathological characteristics of the tumors. We didn't find recidive
      in the observed postoperative follow-up of 4, and 6 years, respectively.
      CONCLUSION: SPT is a rare tumor of the pancreas that is diagnosed primarily in
      young women. The prognosis after surgical treatment was excellent. The
      histopathological analysis is the main procedure in establishing diagnosis,
      regardless the most recent diagnostic procedures.

PMID- 16305106
TI  - [Distal renal tubular acidosis as a cause of osteomalacia in a patient with
      primary Sjogren's syndrome].
AB  - BACKGROUND: One half of the patients with primary Sjogren's syndrome has
      extraglandular manifestations, including renal involvement. The most frequent
      renal lesion is tubulo-interstitial nephritis, which manifests clinically as
      distal tubular acidosis and may result in the development of osteomalacia. CASE
      REPORT: In a 29-year-old female patient, with bilateral nephrolithiasis, the
      diagnosis of primary Sjogren's syndrome, tubulo-interstitial nephritis, distal
      renal tubular acidosis, and hypokalemia were established. She was treated for
      hypokalemia. Two years later she developed bone pains and muscle weakness, she
      wasn't able to walk, her proximal muscles and pelvic bones were painful, with
      radiological signs of pelvic bones osteopenia and pubic bones fractures. The
      diagnosis of osteomalacia was established and the treatment started with Schol's
      solution, vitamin D and calcium. In the following two months, acidosis was
      corrected, and the patient started walking. CONCLUSION: In our patient with
      primary Sjogren's syndrome and interstitial nephritis, osteomalacia was a result
      of the long time decompensate acidosis, so the correction of acidosis, and the
      supplementation of vitamin D and calcium were the integral part of the therapy.

PMID- 16305107
TI  - [Radiation retinopathy in patients treated for sinus and epipharingeal
      malignancies].
AB  - BACKGROUND: Radiation retinopathy is vasculopathy induced by ionising radiation
      delivered by either brachytherapy or teletherapy for ocular and nonocular
      malignancies. The first signs of radiation retinopathy typically occur a few
      months to a few years after the exposure to ionizing radiation. CASE REPORT: In
      the 3 of our patients, changes like capillary telangiectasia, microaneurysms,
      intraretinal hemorrhages, hard exudation, and capillary nonperfusion showed a
      clinical picture of macular edema. Two of the patients were suspected of diabetic
      retinopathy, and 1 patient had optic neuropathy. In our group of patients a
      latent period was between 3 and 8 years. The incidence of radiation retinopathy
      increases significantly with the total doses of radiation above 45 Gy, and, thus,
      it has not been found in the lower doses. CONCLUSION: Radiation retinopathy is a
      diagnostical and therapentical problem. Clinical picture can be identical to that
      of diabetic retinopathy suggesting a common pathophysiologic mechanism of the
      damage to capillary endothelial cells, and the importance of clinical
      examination, anamnesis and fluorescein angiography.

PMID- 16305108
TI  - [Use of extratransference interpretation in psychoanalytic psychotherapy].
AB  - BACKGROUND: In psychoanalytic psychotherapy, the transference analysis takes the
      central position of the work. The work in the extratransference sphere and
      experience in a professional practice with extratransference interventions have
      not been reported much in the literature. Extratransference sphere includes less
      transfering relation to a psychotherapist, transference to other objects, or may
      refer to the external reality rather than the psychic reality or fantasy. CASE
      REPORT: We pointed out extratransference interventions. We demonstrated an
      application of a genetic interpretation and reconstruction, too, which could
      restore and establish the connections between the past and the present, in order
      to understand the influences of the current reality and the past, and helping us,
      further, to resolve the infantile conflicts. CONCLUSION: Interpretation of extra
      transference situations takes an important part of an analytical work and it is
      an essential category of the interpretation. Analytic understanding should
      include transference and extratransference spheres, fantasy and reality, past and
      present. Working with neurotic patterns and character resistance needs an optimal
      choice of intervention in the given moment of the analytic process.
      Extratransference interventions are an essential cathegory of intervention,
      irreplaceable for its effectiveness in the analytic process.

PMID- 16305109
TI  - [Metabolism of gamma-aminobutyric acid and its physiologic role].

PMID- 16305110
TI  - Leukergy and the leukergy test in diseases of the nervous system.

PMID- 16305111
TI  - [Postmortem quantitative study of circulation in the vertebral arteries in
      various head positions in elderly people].

PMID- 16305113
TI  - [Andrologic methods in schizophrenic patients].

PMID- 16305112
TI  - [Depressive stupor--cortical-cerebral atrophy, X-ray and clinical parallelism].

PMID- 16305114
TI  - [A group work with the young people of predelinquent and delinquent behaviour].

PMID- 16305115
TI  - [Photostimulation in clinical electroencephalography].

PMID- 16305116
TI  - [EKG--changes in various types of application of electro-convulsive therapy].

PMID- 16305118
TI  - [Acute cerebrovascular diseases in the Zagreb health services (experience in
      1964)].

PMID- 16305119
TI  - [Cerebral artery diseases].

PMID- 16305117
TI  - [Nervous and mental consequences in children born with forceps].

PMID- 16305120
TI  - [Acute cerebrovascular diseases in the Zagreb health service. Clinical
      experience].

PMID- 16305121
TI  - [Laboratory study of proteins in patients with acute apoplectic insult].

PMID- 16305122
TI  - [Experience with cerebrovascular insults].

PMID- 16305123
TI  - [Patients with apoplexy and hypertension in 1964].

PMID- 16305124
TI  - [On transference].

PMID- 16305125
TI  - [Toxoplasmosis].

PMID- 16305126
TI  - [Schwannoma of the trigeminal nerve].

PMID- 16305127
TI  - [Analysis of a thesis on the nervous origin of pigmented skin naevi].

PMID- 16305128
TI  - [Clinical picture of the Sturge-Weber syndrome].

PMID- 16305129
TI  - [Postencephalitic hallucinatory psychosis].

PMID- 16305130
TI  - [A case of chondromatosis multiplex accompanied by astrocytoma of the pons].

PMID- 16305131
TI  - [The application of non-convulsing electroshock in patients with tracheotomies].

PMID- 16305132
TI  - [Operative result in a case of ventricular type of cerebral cysticercosis].

PMID- 16305133
TI  - [Surmontil in the treatment of depressive conditions].

PMID- 16305134
TI  - [Dr. Marijan Borstnar].

PMID- 16305135
TI  - Coalbed methane: a new source of energy and environmental challenges.

PMID- 16305136
TI  - News on the Antarctic ozone hole.

PMID- 16305137
TI  - Aquatic animal conservation: challenges and perspectives.

PMID- 16305138
TI  - The influence of mycorrhiza on uranium and phosphorus uptake by barley plants
      from a field-contaminated soil.
AB  - BACKGROUND: Recent studies indicated that arbuscular mycorrhizal fungi (AMF) play
      important roles in plant accumulation of uranium (U) from contaminated
      environments, but the impacts of fertilization practices on functioning of the
      symbiotic associations, which are crucial factors influencing plant nutrition and
      growth responses to mycorrhiza, have rarely been considered. MATERIALS AND
      METHODS: In a greenhouse experiment, a bald root barley mutant (brb) together
      with the wild type (wt) were used to test the role of root hairs and AMF in
      uranium (U) uptake by host plants from a U contaminated soil. Nil, 20 and 60 mg
      KH2PO4-P kg(-1) soil were included to investigate the influences of phosphorus
      (P) fertilization on plant growth and accumulation of U. RESULTS: Dry matter
      yield of barley plants increased with increasing P additions and wt produced
      significantly higher dry weight than brb. Mycorrhiza markedly improved dry matter
      yield of both genotypes grown at nil P, whereas only brb responded positively to
      mycorrhiza at 20 mg P kg(-1). At the highest P level, mycorrhiza resulted in
      growth depressions in both genotypes, except for the roots of wt. In general,
      plant P concentrations increased markedly with increasing P additions and in
      response to mycorrhiza. Mycorrhiza and P additions had no significant effects on
      shoot U concentrations. However, root U concentrations in both genotypes were
      significantly increased by mycorrhiza. On the other hand, shoot U contents
      increased with increasing P levels, while 20 mg P kg(-1) stimulated, but 60 mg P
      kg(-1) marginally affected the U accumulation in roots. Root length specific U
      uptake was moderately enhanced both by root hairs and strongly enhanced by
      mycorrhiza. Moreover, non-inoculated plants generally had higher shoot-root
      ratios of U content than the corresponding inoculated controls. CONCLUSION: Our
      study shows that AMF and root hairs improves not only P acquisition but also the
      root uptake of U, and mycorrhiza generally decreases U translocation from plant
      root to shoot. Hence, mycorrhiza is of potential use in the phytostabilization of
      U contaminated environments. PERSPECTIVES: The complex impacts of P on U
      accumulation by barley plants suggested that U behavior in mycorrhizosphere and
      translocation along the soil-fungi-plant continuum as affected by fertilization
      practices deserve extensive studies for optimizing the function of mycorrhizal
      associations for phytoremediation purposes.

PMID- 16305139
TI  - Growth of plants on TBT-contaminated harbour sludge and effect on TBT removal.
AB  - BACKGROUND: Worldwide, large amounts of sediments have to be dredged annually
      from waterways and harbours. These sediments are sometimes polluted with a
      variety of toxic compounds. In some countries, including Belgium, the load with
      the biocide tributyltin (TBT) from ship coatings prohibits the dumping of harbour
      sludge into the sea. Land-based dumping is a commonly used alternative.
      OBJECTIVE: This research investigated the feasibility to use land-deposited
      harbour sludge for plant production. In a field trial, the growth of 38 more or
      less salt-tolerant plant species on low and high TBT-contaminated sediments was
      studied. The elimination of TBT from sludge with and without vegetation was
      compared. The uptake of TBT and its degradation products di- and monobutyltin
      (DBT and MBT) into harvest products under field conditions was determined.
      EXPERIMENTAL SET-UP: Sediments dredged in May 2003 from the brackish waters of
      the port of Antwerp were analysed in the laboratory for soil texture, pH,
      electroconductivity, sodium, magnesium, potassium, calcium, ammonium, nitrate,
      total nitrogen, chloride, sulphur and the organotins TBT, DBT and MBT. The
      sediments were lagooned for one year to dewater, desalinate and improve their
      structure. Salt-tolerant domestic and wild plants were selected and sown in May
      2004. In August 2004, plants were harvested and the produced biomass was
      determined. Samples were taken from vegetated and non-vegetated top and bottom
      sediments and from plants growing above soil and analysed for TBT, DBT and MBT.
      RESULTS: The fresh sediments showed a good supply with nutrients and a neutral
      pH, but were rather saline (EC 14 mS cm(-1) of the saturated paste extract). The
      salinity decreased to 3.7 mS cm(-1) during lagoonation. The high and the low
      contaminated sediment had initially 43 and 1.6 mg TBT kg(-1) dry weight,
      respectively. Besides TBT, several other contaminants were present in the
      sediments at critical levels. The biomass production of the plant species from
      the field trial ranged from 0.2 to 13 tons dry mass per hectare. Plants
      performing excellently were barley, sorghum, rape seed, a clover/grass mix and
      reed. If at all, a positive influence of TBT on plant growth was seen. TBT was
      degraded significantly faster (>40%) below barley. The uptake of TBT, DBT and MBT
      into stem and leaves of reed, grass and clover was very low, but measurable and
      not related to concentrations in soil. No uptake of TBT or its metabolites into
      corn of barley was found. DISCUSSION: This study confirmed former results: the
      toxicity of TBT to higher plants is low, and even high levels in soils would not
      be a hindrance for crop production. The removal of TBT seemed to be increased by
      both lagooning and plant growth, although the target values for sea dumping in
      use in certain European countries were not reached. A plausible explanation for
      the faster degradation of TBT under vegetation is that oxygen is a limiting
      factor, and plants dewater the soil, thus aerating it. The uptake of the
      organotins TBT, DBT and MBT into harvest products is probably due to attached
      soil particles. CONCLUSIONS: To summarize, barley was the optimal species: it
      grew very well despite the salinity of the dredged sediments, it had a
      significantly positive effect on TBT removal; it showed no measurable uptake of
      TBT or the other butyltins into the harvested product; and it is a cash crop well
      established in European agriculture. OUTLOOK: The amounts of dredged sediments
      are high, and good soils are becoming increasingly rare. The feasibility of using
      dredged sediments for non-food production, such as energy crops, should be
      investigated by a critical risk assessment.

PMID- 16305140
TI  - Uptake and modeling of pesticides by roots and shoots of parrotfeather
      (Myriophyllum aquaticum).
AB  - INTENTION, GOAL, SCOPE, BACKGROUND: Aquatic plants have a great potential to
      function as in situ, on-site biosinks and biofilters of pollutants. They are used
      for phytoremediation and phytotoxicity studies. Pesticide uptake studies are very
      important to predict contaminant accumulation, translocation, and transformation.
      There are a lot of models which have been developed for emergent plants, but
      there are not any existing models for submerged aquatic plants for assessing
      pesticide uptake. OBJECTIVE: In this study, uptake of selected pesticides in
      parrotfeather (Myriophyllum aquaticum) were studied and the results were modeled
      with the aid of Log Kow and the concentration of pesticides. At the end, the
      developed model was compared to other existing models. METHODS: The test was
      conducted with parrotfeather as a model plant. The bioassay and cultivation of
      this plant were examined. Pesticide uptake by roots and shoots was determined
      using 14C-radiolabeled materials. RESULTS AND DISCUSSION: The results were fitted
      with an equation that showed a relationship between uptake and lipophilicity of
      pesticides. The model was compared with other pesticide uptake models developed
      for other plants. Atrazine and cycloxidim were taken up more by roots than by
      shoots in comparison to other pesticides used. The total uptake, both in shoots
      and roots, was lower than for terbutryn and trifluralin. The best appropriate
      model was developed from the results against the other models seen in the
      literature. The concentration factors (Root Concentration Factor (RCF) and
      Submerged Shoot Concentration Factor (SSCF)) increased with a higher Kow of the
      substances. The Submerged Shoot Concentration Factor (SSCF) revealed a better
      relationship of the chemicals than did the Root Concentration Factor (RCF).
      CONCLUSIONS: In this study, an uptake model was developed for rooted, submerged
      aquatic plants. Further studies are necessary to develop and compare models with
      different plants and pesticides. RECOMMENDATION AND OUTLOOK: Such studies as this
      one may be extended to other environmental pollutants in the aquatic ecosystem
      and may be employed to evaluate the possibility of using different plants in
      phytoremediation studies.

PMID- 16305141
TI  - Endocrine disruption of water and sediment extracts in a non-radioactive dot
      blot/RNAse protection-assay using isolated hepatocytes of rainbow trout.
AB  - GOAL, SCOPE AND BACKGROUND: In order to evaluate the estrogenic activity of
      sediments and XAD water extracts of selected sites of the catchment area of the
      River Neckar, a river system in Southern Germany, an integrative assessment
      approach was used to assess the ecological hazard potential of endocrine
      disrupting compounds in sediment and water. METHODS: The approach is based on
      estrogen receptor-mediated vitellogenin synthesis induced in isolated hepatocytes
      of rainbow trout and quantified in a non-radioactive dot blot/RNAse protection
      assay in parallel to comprehensive chemical analyses of estrogenic substances.
      RESULTS AND DISCUSSION: Numerous investigated extracts revealed an estrogen
      activity comparable to that of the positive control (1 nM 17beta-estradiol
      corresponding to 270 ng/L in the test medium). Based on a concentration factor of
      30 in the extracts and a recovery of XAD resins of approximately 80%, 17beta
      estradiol equivalent concentrations between 20 and 26.7 ng/L could be calculated
      downstream of a sewage treatment plant (< 0.1 ng/L for a reference site). A
      comparison of the bioassay-derived Bio-TEQs (toxicity equivalents) and the Chem
      TEQs revealed a high correlation with a Pearson coefficient of 0.85, indicating
      that the same ranking of the samples could be obtained with respect to the
      endocrine disrupting potential with both chemical and bioanalytical analysis.
      However, the TEQ concentrations computed from chemical analyses were
      significantly lower than the bioassay-derived TEQ concentrations. In fact, in
      none of the samples, more than 14% of the vitellogenin-inducing potency could be
      attributed to the substances (steroids, alkylphenols, bisphenol A,
      diethylstilbestrol) analyzed. A comparison of the endocrine disrupting potential
      of sediments extracted by the solvents acetone and methanol revealed lower
      biological effects for acetone-extracted samples. Possible reasons may be a
      masking of endocrine effects in acetone extracts by cytotoxicity, a low
      extraction efficiency of the solvent acetone, or anti- estrogen potencies of some
      extracted sediment compounds. Using a mass balance approach, the contribution of
      the compounds analyzed chemically (Chem-TEQs) to the total endocrine activity
      (Bio-TEQs) was calculated. Based on the very low detection limits, particularly
      of the steroids with their high TEF factors, results revealed that a calculation
      of the Chem-TEQs is associated with considerable scale inaccuracy: Whereas only 7
      15% of the biological effectiveness (Bio-TEQs) could be explained by endocrine
      substances identified above the detection limits, the assumption of
      concentrations slightly below the given detection limits would result in a
      significant over estimation (137-197%) of the Bio-TEQs. Even the interassay
      variation of the dot blot assay with different fish donors for primary hepatocyte
      (factor 2-2.5) is relatively low, when compared to the large range of the Chem
      TEQ concentrations (factor 20) obtained when applying different modes of
      calculation. CONCLUSIONS AND OUTLOOK: Overall, only a minor portion of the
      endocrine activity detected by bioassays could be linked to compounds identified
      by chemical analysis. In vitro assays for assessment of endocrine activities are
      useful as sensitive integrating methods that provide quantitative estimates of
      the total activity of particular receptor-mediated responses. Although
      discrepancies may also result from different bioanalytical approaches, it is
      overall likely that bioanalytical and not chemical analytical approaches give the
      correct estimate of endocrine disrupting potencies in environmental samples. As a
      conclusion, assessment of endocrine disruption based on chemical analysis alone
      does not appear sufficient and further research into the spectrum of substances
      with potential endocrine activity as well as into additive or even synergistic
      effects in complex environmental samples is urgently needed.

PMID- 16305142
TI  - Bacterial community structure analyses to assess pollution of water and sediments
      in the Lake Shkodra/Skadar, Balkan Peninsula.
AB  - GOAL, SCOPE AND BACKGROUND: Lake Skadar is the largest lake of the Balkan
      Peninsula, located along the Montenegro-Albanian border. The unique features of
      the lake and wide range of endemic, and rare or endangered plant and animal
      species, resulted in the classification of the Skadar as a wetland site of
      international significance. In spite of its importance, the lake is influenced by
      inflowing waters from the river Moraca and other regional rivers contaminated by
      the industry, municipal and agricultural activities in the area. Therefore, the
      lake has been the subject of various physical, chemical, biological and
      toxicological examinations. However, community-level analyses are most relevant
      to assess the effect of stressors on aquatic ecosystems. In the present study,
      bacterial community structure among differently polluted sites of the lake was
      compared using a genetic fingerprinting technique. METHODS: Water and sediment
      samples were collected from five differently polluted sampling sites on the Lake
      Skadar in spring and autumn of the same year. The bacterial community structure
      in the samples was characterized and compared by temporal temperature gel
      electrophoresis (TTGE) analysis of polymerase chain reaction-amplified bacterial
      16S rRNA genes. RESULTS AND DISCUSSION: The TTGE analysis resulted in many
      distinguishable and reproducible band patterns, allowing a reliable comparison of
      bacterial communities among sampling sites. Results on the bacterial community
      structure revealed that three of the selected locations can be considered as
      sites that have not shown any pollution degradation determined by our method, due
      to similar structure of a bacterial community in the sediment samples. On the
      other hand, significant shifts in the bacterial community structure in the mouth
      of the rivers Moraca and Plavnica were shown. Since the results coincide with
      some of the bioassays and chemical analysis performed previously, the changes in
      bacterial community structure are explained as an effect of antropogenic
      pollution on the lake ecosystem by waters of the river Moraca and the stream
      Plavnica. CONCLUSION: The TTGE has proven to be an efficient and reliable method
      to monitor bacterial dynamics and community shifts in aquatic environments,
      especially in sediments. Within the variety of environmental quality assessments,
      the use of TTGE analyses from bacterial communities is strongly recommended,
      particularly as an initial investigation. However, in any conclusion on the state
      of the environment, the TTGE results should be combined to some other biological,
      chemical and hydrological data. RECOMMENDATION AND OUTLOOK: Since prokaryotes are
      a crucial group of organisms in the biosphere, the ecosystem function studies are
      largely based on bacterial communities. Therefore, bacterial community structure
      analysis should be a part of an integrated weight of evidence approach in
      pollution assessment. In case of Triad approach, consisting of chemical analyses,
      bioassays, and community studies in the field, the TTGE bacterial community
      structure analyses should be placed in the later Triad leg. In comparison to
      other community studies, based on various biotic indices, the TTGE bacterial
      community analysis has proven to be very sensitive, reliable and less time
      consuming.

PMID- 16305143
TI  - Removal of microcystins by phototrophic biofilms. A microcosm study.
AB  - BACKGROUND, AIMS AND SCOPE: Microcystins (MCs) are a family of natural toxins
      produced by cyanobacteria (blue-green algae). As a result of eutrophication,
      massive cyanobacterial blooms occur more frequently and MCs represent important
      contaminants of freshwater ecosystems. Bacterial biodegradation is considered a
      main mechanism for MC breakdown in environmental conditions. While existing
      studies were mostly focused on MC biodegradation by planktonic bacteria, our
      experiments examined the fate and kinetics of MC degradation in river-originated
      phototrophic biofilms and investigated factors influencing the rate of MC
      removal. METHODS: The fate of dissolved MCs was studied in laboratory microcosms
      with different composition (containing water only, water with phytoplankton
      and/or phototrophic biofilms). Biofilms originated from river ecosystem were pre
      incubated under various conditions (with/without presence of cyanobacterial
      biomass or model organic substrates: glucose and protein--casein). Changes in MC
      concentration (0-14 days) in water columns were measured by HPLC-DAD after
      external additions of purified MCs (160 microg L(-1), MC-LR and MC-YR), and
      halftimes (t1/2) of MC removal were estimated. RESULTS AND DISCUSSION: The slow
      degradation of MC was revealed in tap water (t1/2 approximately 14 days) and
      river water without cyanobacteria (t1/2 approximately 8 days). Enhanced removal
      occurred in the presence of natural planktonic cyanobacteria (t1/2 approximately
      44 h), most probably due to microorganisms associated with the biomass of
      cyanobacterial bloom. More rapid MC elimination occurred in the variants
      containing phototrophic biofilms, and was particularly pronounced at those
      biofilms pre-cultivated in the presence of cyanobacterial blooms (t1/2
      approximately 20 h). Much slower removal was observed in the variants simulating
      possible substrate-dependent induction of microorganism metabolism (biofilms pre
      incubated with glucose: t1/2 approximately 35 h, and casein: t1/2 approximately
      80 h). After termination of experiments, total amounts of MCs accumulated in the
      biofilms were below 5% of the initial toxin level revealing significant
      biodegradation processes. CONCLUSION: The microcosm studies contributed to
      understanding of the environmental fate of MCs and revealed a rapid
      biodegradation by phototrophic biofilms. The rate of MC elimination depends on
      history of biofilm community, previous contact with cyanobacteria seems to be a
      selective factor improving the biodegradation potential. RECOMMENDATION AND
      OUTLOOK: Our results experimentally showed a positive role of biofilms in MC
      elimination during water treatment processes such as bank filtration or slow sand
      filtration, and could eventually serve for further research of biofilm-based
      technological applications for MCs removal in small-scale drinking water
      treatment facilities.

PMID- 16305144
TI  - Multivariate statistics of the pyrolysis products of high molecular components in
      pulping wastewaters to explain their toxicity.
AB  - BACKGROUND, AIM AND SCOPE: At present, large-scale paper manufacture involves
      delignification and bleaching by elemental chlorine free (ECF), or totally
      chlorine free (TCF) processes. The wastewater is purified by secondary treatment
      (mechanical, chemical and biological) which removes most of the toxic substances
      from the discharge. However, we found residual toxicity in the high molecular (>
      1000 D) matter (HMWM) of the discharge by test of the RET (reverse electronic
      transfer) inhibition. This fraction consists mainly of polydispersed lignin (LIG)
      and carbohydrate (CH) macromolecules. Structural units in these molecules are
      studied by pyrolysis gas chromatography/mass spectrometry (Pyr-GC/MS). In the
      present work, our aim was to find out those structural units which could explain
      the RET toxicity of LIG or CH molecules. We compared statistically RET toxicity
      values of the HMWM samples from treated wastewaters of pilot pulping experiments
      and intensity variation of the pyrolysis product gas chromatograms of these
      samples. This application is a novel study procedure. METHODS: Pyrolysis products
      (Py-GC/MS results) and inhibition of RET (reverse electronic transport toxicity)
      as TU50 and TU20 of HMWM (High Molecular Weight Material; Mw > 1000 D) were
      compared by multivariate statistics. The samples were from laboratory pilot
      stages of TCF (Totally Chlorine Free) and ECF (Elemental Chlorine Free)
      manufacture of softwood pulp. Py-GC/MS was done without and with the addition of
      TMAH (Tetra Methyl Ammonium Hydroxide). The name and structure of each abundant
      fragment compound was identified from its retention time and mass spectrum
      compared to authentic reference compounds or literature. Four sets of Toxicity
      Units (TUs) and GC peak areas of the pyrolysis fragments were obtained. The data
      were normalized by division with LIG (lignin content of each sample). TU values
      were dependent and the fragment values independent (explanatory) variables in
      statistical treatments by SPSS system. Separate analyses of correlations,
      principal components (PCA) and stepwise multiple linear regression (SMLR) were
      performed from the four sample sets TCF and ECF with and without TMAH. RESULTS
      AND DISCUSSION: From the CH fragments, 2-furfural in TCF, and from the LIG
      fragments, styrene in ECF showed the highest probabilities of originating from
      source structures of toxicity. Other possible compounds in concern were indicated
      to be CH fragment 2-methyl-2-cyclopenten-1-one in ECF and LIG fragments 2-methoxy
      4-methylphenol, 4,5-dimethoxy-2-methylphenol and 2-methylphenol in TCF.

PMID- 16305145
TI  - Biotic and abiotic transformations of methyl tertiary butyl ether (MTBE).
AB  - BACKGROUND: Methyl tertiary butyl ether (MTBE) is a fuel additive which is used
      all over the world. In recent years it has often been found in groundwater,
      mainly in the USA, but also in Europe. Although MTBE seems to be a minor toxic,
      it affects the taste and odour of water at concentrations of < 30 microg/L.
      Although MTBE is often a recalcitrant compound, it is known that many ethers can
      be degraded by abiotic means. The aim of this study was to examine biotic and
      abiotic transformations of MTBE with respect to the particular conditions of a
      contaminated site (former refinery) in Leuna, Germany. METHODS: Groundwater
      samples from wells of a contaminated site were used for aerobic and anaerobic
      degradation experiments. The abiotic degradation experiment (hydrolysis) was
      conducted employing an ion-exchange resin and MTBE solutions in distilled water.
      MTBE, tertiary butyl formate (TBF) and tertiary butyl alcohol (TBA) were measured
      by a gas chromatograph with flame ionisation detector (FID). Aldehydes and
      organic acids were respectively analysed by a gas chromatograph with electron
      capture detector (ECD) and high-performance ion chromatography (HPIC). RESULTS
      AND DISCUSSION: Under aerobic conditions, MTBE was degraded in laboratory
      experiments. Only 4 of a total of 30 anaerobic experiments exhibited degradation,
      and the process was very slow. In no cases were metabolites detected, but a few
      degradation products (TBF, TBA and formic acid) were found on the site, possibly
      due to the lower temperatures in groundwater. The abiotic degradation of MTBE
      with an ion-exchange resin as a catalyst at pH 3.5 was much faster than
      hydrolysis in diluted hydrochloric acid (pH 1.0). CONCLUSION: Although the
      aerobic degradation of MTBE in the environment seems to be possible, the specific
      conditions responsible are widely unknown. Successful aerobic degradation only
      seems to take place if there is a lack of other utilisable compounds. However,
      MTBE is often accompanied by other fuel compounds on contaminated sites and
      anaerobic conditions prevail. MTBE is often recalcitrant under anaerobic
      conditions, at least in the presence of other carbon sources. The abiotic
      hydrolysis of MTBE seems to be of secondary importance (on site), but it might be
      possible to enhance it with catalysts. RECOMMENDATION AND OUTLOOK: MTBE only
      seems to be recalcitrant under particular conditions. In some cases, the
      degradation of MTBE on contaminated sites could be supported by oxygen. Enhanced
      hydrolysis could also be an alternative.

PMID- 16305146
TI  - EPA risk assessment principles and practices. BOSC (board of scientific
      counselors) workshop, February 2-3, 2005, Washington, DC.

PMID- 16305147
TI  - Agent Orange and dioxin remediation workshop: Hanoi, Viet Nam, 16-18 August 2005.

PMID- 16305148
TI  - [Rheumatic changes in the central nervous system].

PMID- 16305149
TI  - [Pathophysiology of static tremor in Parkinsonism].

PMID- 16305150
TI  - [Work capacity evaluation in neuropsychiatry].

PMID- 16305151
TI  - [Problems of modern psychopharmacology].

PMID- 16305153
TI  - [Our experieinces in acute cerebrovascular disease].

PMID- 16305152
TI  - [Investigations of proteins by immuno-electrophoresis in serum in schizophrenic
      patients].

PMID- 16305154
TI  - [Modern understanding of hypochondria].

PMID- 16305155
TI  - [Psychiatric care in families of delinquents].

PMID- 16305156
TI  - [Determination of the conduction velocity of motor nerves and its diagnostic
      value].

PMID- 16305157
TI  - [Neurological disorders in acute porphyria. Report of two cases].

PMID- 16305158
TI  - [Neurologic changes in adenovirus infection in children].

PMID- 16305159
TI  - [Neuropsychiatric aspects of endemic cretinism in the Koprivnica District].

PMID- 16305160
TI  - [Clinical and radiologic analysis of aortic arch syndrome].

PMID- 16305161
TI  - [Syringomyelia in Macedonia and southern parts of Serbia].

PMID- 16305162
TI  - [Pellagra psychosis in Istria].

PMID- 16305163
TI  - [Schizophrenia in siderocalcinosis of the central ganglia].

PMID- 16305164
TI  - [Treatment of patients with mental disorders in Serbia until the founding of the
      psychiatric hospital in 1861].

PMID- 16305165
TI  - [Importance of tracheotomy in prevention of complications in craniocerebral
      injuries].

PMID- 16305166
TI  - [Therapeutic effects of butyrilperazine].

PMID- 16305167
TI  - [Deseril (methysergide) in the treatment of vascular migraine headache].

PMID- 16305168
TI  - [Symptomatic psychoses during treatment with cycloserine].

PMID- 16305169
TI  - [Treatment of forensic cases of pseudodementia with electronarcosis].

PMID- 16305170
TI  - [Treatment of enuresis nocturna with tofranil].

PMID- 16305171
TI  - [Psychotherapy in the United States].

PMID- 16305172
TI  - [Genotoxicity of 43 existing food additives].

PMID- 16305173
TI  - [Multi-residue method for screening of pesticides in crops by liquid
      chromatography with tandem mass spectrometry].
AB  - A simple and rapid method was developed for the screening of 82
      pesticides/metabolites in a wide variety of crops, using solid-phase extraction
      and liquid chromatography with tandem mass spectrometry (LC/MS/MS). After
      extraction with methanol, the filtered extracts were made up to 100 mL and a 2 mL
      aliquot was subjected to solid-phase extraction. Co-extractives were removed with
      a C18 mini-column, while pesticides were retained on 3 kinds of mini-columns
      (HLB, SAX, activated carbon), and then eluted with acetonitrile. Analysis was
      performed by LC/MS/MS, and MS acquisition parameters were established in positive
      and negative ESI modes. The utility of the method was demonstrated by the
      analysis of 6 crops (carrot, cabbage, onion, spinach, lemon, brown rice) and one
      mixed vegetable juice. Of 82 compounds tested, 75 in carrot and 62 in lemon were
      obtained with recoveries ranging from 70-120%. For all samples tested, 75
      compounds could be obtained with recoveries of over 50%, and the detection limits
      of most compounds were lower than 0.01 microg/g. This method provides acceptable
      performance for analysis of these 75 compounds. Further, by using aliquots of the
      extracts with small-scale mini-columns, purified samples could be obtained. This
      proposed method with small matrix effects, is effective and suitable for
      screening of multiple residual pesticides by using LC/MS/MS.

PMID- 16305174
TI  - Analysis of the constituents in jojoba wax used as a food additive by LC/MS/MS.
AB  - Jojoba wax is a natural gum base used as a food additive in Japan, and is
      obtained from jojoba oil with a characteristically high melting point. Although
      the constituents of jojoba oil have been reported, the quality of jojoba wax used
      as a food additive has not yet been clarified. In order to evaluate its quality
      as a food additive and to obtain basic information useful for setting official
      standards, we investigated the constituents and their concentrations in jojoba
      wax. LC/MS analysis of the jojoba wax showed six peaks with [M+H]+ ions in the
      range from m/z 533.6 to 673.7 at intervals of m/z 28. After isolation of the
      components of the four main peaks by preparative LC/MS, the fatty acid and long
      chain alcohol moieties of the wax esters were analyzed by methanolysis and
      hydrolysis, followed by GC/MS. The results indicated that the main constituents
      in jojoba wax were various kinds of wax esters, namely eicosenyl octadecenoate
      (C20:1-C18:1) (1), eicosenyl eicosenoate (C20:1-C20:1) (II), docosenyl
      eicosenoate (C22:1-C20:1) (III), eicosenyl docosenoate (C20:1-C22:1) (IV) and
      tetracosenyl eiosenoate (C24:1-C20:1) (V). To confirm and quantify the wax esters
      in jojoba wax directly, LC/MS/MS analysis was performed. The product ions
      corresponding to the fatty acid moieties of the wax esters were observed, and by
      using the product ions derived from the protonated molecular ions of wax esters
      the fatty acid moieties were identified by MRM analysis. The concentrations of
      the wax esters I, II and III, in jojoba wax were 5.5, 21.4 and 37.8%,
      respectively. In summary, we clarified the main constituents of jojoba wax and
      quantified the molecular species of the wax esters without hydrolysis by
      monitoring their product ions, using a LC/MS/MS system.

PMID- 16305175
TI  - [Mycological examination of domestic unpolished rice and mycotoxin production by
      isolated Penicillium islandicum].
AB  - Fungi growing on domestic rice were examined from April to June, 2003. One
      hundred samples of rice, which had been harvested in the autumn of 2002, were
      collected from the local market, and 15 samples of stored rice, which had been
      harvested in 2001 and stored in warehouses under government control, were used as
      samples. From each sample, 50 grains (100 grains in total) were plated on potato
      dextrose agar (PDA) and malt yeast 40% sucrose agar (M40YA) containing
      chloramphenicol after being washed with sterile distilled water to remove any
      microorganisms on the surface, and incubated at 25 degrees C for a week. For most
      of the rice samples harvested in the preceding year, the proportion of grains
      infected with fungi was less than 20% of the total grains tested. In about half
      the samples of rice stored for one and half years, more than 80% of the grains
      were infected with fungi that grew on M40YA. The major genera of fungi isolated
      from the rice harvested in the preceding year were Penicillium and Alternaria,
      and those from the rice stored for one and a half years were Aspergillus,
      Penicillium and Eurotium. P. islandicum, A. versicolor, A. ochraceus and others
      were isolated as possible mycotoxin-producers in the mycoflora of domestic rice.
      P. islandicum was isolated from 3 samples, and 82% of the grains were infected
      with this fungus in one sample. All three isolates from these samples appeared to
      produce luteoskyrin on Czapek yeast extract agar, based on TLC and HPLC analysis.

PMID- 16305176
TI  - [Growth inhibition of Vibrio parahaemolyticus in seafood by tabletop dry ice
      cooler].
AB  - Tabletop dry ice coolers (three types; dome model, cap model and tripod model),
      which are used in kitchens and hotel banquet halls to refrigerate fresh seafood,
      were investigated to determine whether growth of Vibrio parahaemolyticus was
      inhibited by their use. On TSA plates containing 1.8% NaCl and fresh seafood
      (fillets of squid, pink shrimp and yellowtail), V. parahaemolyticus (O3:K6, TDH+)
      inoculated at 4 to 5 log CFU/sample and left at ambient temperature (25 degrees
      C) grew by 1.0 to 2.8 orders in 4 hours. In contrast, with tabletop coolers no
      significant increase in viable count occurred in 3 to 4 hours, confirming that
      tabletop coolers inhibited the growth of V. parahaemolyticus. The temperature in
      each tabletop cooler was kept below 10 degrees C for 80 to 135 min, though the
      CO2 gas concentration in them remained high for only a short time (0 to 75 min).
      It was presumed that the refrigeration function mainly contributed to growth
      inhibition. Our results indicate that tabletop dry ice coolers are helpful for
      prevention of food-borne disease due to V. parahaemolyticus in food-service
      locations, such as kitchens and banquet halls.

PMID- 16305177
TI  - [Analysis of formaldehyde, acetaldehyde and oligomers in recycled polyethylene
      terephthalate].
AB  - Formaldehyde (FA), acetaldehyde (AA) and oligomers in recycled polyethylene
      terephthalate (PET) were analyzed by HPLC. All of the physically recycled PET
      contained detectable levels of FA, AA and oligomers, and the levels were almost
      the same as in used bottles. Most superclean-like and chemically recycled PET
      contained lower levels than new pellets. These compounds showed no decrease upon
      physical recycling, but showed a marked decrease upon superclean-like recycling.
      In PET sheets made using physically recycled PET, FA was decreased, though AA was
      increased by the sheeting process as same as new one. FA, AA and oligomers
      originated from PET resin and their levels in recycled products were almost
      equivalent to those in new products. It was concluded that there is no particular
      safety concern about their presence in recycled PET.

PMID- 16305178
TI  - [Inter-laboratory study for validation of a Japanese official analytical method
      for determination of patulin in apple juice].
AB  - To validate a modified version of AOAC official method of analysis 995.10 as an
      official standard in Japan for determination of patulin in apple juice, an inter
      laboratory study was performed in 11 laboratories using a non-contaminated
      sample, 2 naturally contaminated samples and 2 spiked samples of apple juice. For
      naturally contaminated apple juices, the relative standard deviations for
      repeatability and reproducibility were 3.2, 7.1% and 10.0, 21.7%, respectively.
      HORRAT values were 0.4, 0.9. The average recovery of patulin from spiked sample
      was 83.7%. The limit of quantification was calculated as 10 microg/kg. From these
      results, the method was thought to be suitable as an official standard for
      determination of patulin in apple juice in Japan.

PMID- 16305179
TI  - [Confirmation of non-permitted dyes detected in Akasu (red vinegar) by LC/MS].
AB  - Suitable liquid chromatography/mass spetrometry (LC/MS) conditions were examined
      for Amaranth, Red 2G (R2G), Azo Rubine (Azo), Fast Red E (FRE) and Brilliant Blue
      FCF, which were detected in Akasu, a red vinegar made in Hong Kong from sake
      lees, on both thin layer chromatography (TLC) and photodiode array high
      performance liquid chromatography (PDA-HPLC). Molecular-related ions for each dye
      were detected with excellent sensitivity by LC/MS using electro-spray ionization
      with negative ion mode, capillary voltage 3.00 kV, cone voltage 50 V and
      desolvation temperature 400 degrees C. LC/MS analysis of refined Akasu under
      these conditions enabled us to obtain clear mass spectra of R2G, Azo and FRE,
      which were present at trace levels in the Akasu. The results were consistent with
      those from TLC and PDA-HPLC. These experiments suggested that LC/MS analysis is
      applicable for confirmation of dyes in food.

PMID- 16305180
TI  - [Baird-Parker agar medium and rabbit plasma fibrinogen agar medium in Japanese
      industrial standard].

PMID- 16305181
TI  - [BSE and problems with food safety measures in Japan].

PMID- 16305182
TI  - [Risk assessment of the antibiotic-resistant bacteria derived from antibiotics
      added to livestock feed].

PMID- 16305183
TI  - [Safety assessment of genetically modified foods].

PMID- 16305184
TI  - [Current situation and future perspective in FOSHU (foods for specified health
      uses)].

PMID- 16305185
TI  - [The policy to ensure food safety in Tokyo metropolis--drew up food safety
      promotion plan--].

PMID- 16305186
TI  - [Food safety and feeling of safe --risk communication--].

PMID- 16305187
TI  - [Rethinking criminal responsibility: practical application of operational
      diagnosis and gnostic into expert testimony].
AB  - There had been argument concerning the difference between the agnostic approach
      and the gnostic approach to the psychiatric perspective of criminal
      responsibility until the landmark ruling by the 3rd court of the Japanese Supreme
      Court in 1984. The decision upheld the gnostic approach and affirmed that the
      defendant's criminal responsibility should be based on such factors as
      psychopathology, motive, modus operandi, situation surrounding the crime, and pre
      morbid personality, as long as the offense was not directly motivated by the
      delusion or hallucination. The gnostic explanation includes so many various
      factors that the psychiatric testimony cannot easily be objective, while agnostic
      experts can find a conclusion about criminal responsibility only by psychiatric
      diagnosis. To establish a standard, the authors summarized the means of
      determination of criminal responsibility. The authors also discussed various
      topics related to criminal responsibility including Asperger's syndrome, illicit
      drug intoxication, and prescribed drug intoxication.

PMID- 16305188
TI  - [What can psychiatrists do for patients who want to die?].
AB  - The desire to commit suicide frequently arises in mentally ill patients, but how
      to present a persuasive argument to dissuade these patients from committing
      suicide remains a difficult challenge. This issue is considered below, while
      referring to the highly publicized Chabot case, in which a psychiatrist assisted
      in the suicide of a patient who was depressed by the loss of two sons under
      unfortunate circumstances. Euthanasia, or assisted suicide, has generally been
      criticized for the following reasons: 1) It is impossible to ascertain whether
      the free will of the patient, considered to be the fundamental basis for self
      determination, was intact at the time of performing the procedure. 2) If the
      practice becomes widespread, then there exists the potential for vulnerable
      patients to receive perfunctory medical care; 3) Frequently, the desire to die is
      transient and ambivalent; 4) The ramifications associated with death extend
      beyond the individual and may be particularly acute with the family. Each of
      these arguments can be used as a logical counterargument to suicide, and, to the
      extent that they are based on the fact that death is irreversible, they are
      effective. However, although we are generally opposed to euthanasia and assisted
      suicide, we believe that these arguments are ill-suited for convincing individual
      patients not to commit suicide. An overview of discussions of the Chabot case is
      considered useful for reflecting on ways to prevent suicide, including
      psychotherapeutic relationships. The issue of how to respond to patients at a
      high risk of suicide in Japan is also considered based on these discussions.
      Lacking sufficient criteria for determining the competence of a patient who wants
      to die, the position that medical treatment can be provided simultaneously while
      assessing the competence of the patient is considered meaningless. In addition,
      there is a danger that strongly promoting the treatment of depression in patients
      at high risk for suicide denies the patient his or her free will by inviting
      excessive medicalization and encroaching on the patient's "freedom to die." We
      believe that the only course one can take is to get close to the patient's pain
      and anguish, while directly confronting the dilemma of the patient's right to die
      versus assisting the patient to live.

PMID- 16305189
TI  - [Ethics in clinical psychiatry].
AB  - Although the significant influence of American bioethics on the Japanese medicine
      and medical education it does not mention however sufficiently on the psychiatric
      ethics, so we have to discuss once more what ethical issues stand in the area of
      clinical psychiatry. In this paper we point out the issues on freedom or
      restraint of patients, ability of working, psychotherapeutic ethics, informed
      consent and on using of psychotropic drugs, and comment upon the historical
      origin of these issues. Disregarding these special issues however, we will
      mention also the question what is fundamentally ethical in clinical psychiatry.
      This question relates very nearly with the opposition of materialism and
      spiritualism in the whole history of psychiatry, so we have to review how these
      oppositions such as body vs. soul, organic vs. psychogenic, biological vs.
      psychoanalytical, are treated in the history. As a result of the history it can
      be expressed that it may cause unethical occurrences if one extremely represents
      materialism or spiritualism, or reversely the holistic position of both of them
      to integrate and dissolve the contradiction of these alternative relations.
      Ethical is, rather, to stay in the middle or transitional area between
      materialism and spiritualism, and to retain this position always in our
      fundamental clinical attitude, even if it is very hard and stressful, for it
      demands to be tolerant of severe ambiguity.

PMID- 16305190
TI  - A transition-metal-catalyzed enediyne cycloaromatization.
AB  - The pentamethylcyclopentadienyl iron cation, generated from [(eta5
      C5Me5)Fe(NCMe)3]PF6, triggers the room temperature cycloaromatization of acyclic
      and alicyclic enediynes, in the presence of either 1,4-cyclohexadiene or
      terpinene as the hydrogen-atom donor, to give metal-arene products in good to
      excellent yields. Photolysis of the metal-arene complexes liberates the arene
      from the metal in excellent yield. The first demonstration of a transition-metal
      catalyzed cycloaromatization of conjugated enediynes has been achieved under
      photochemical conditions utilizing either [(eta5-C5Me5)Fe(NCMe)3]PF6 or [(eta5
      C5Me5)Fe(eta6-1,2-(Prn)2C6H4)]PF6 as the catalyst precursor. The use of a metal
      and light has led to a convenient method for cycloaromatization of a trans
      enediyne.

PMID- 16305191
TI  - A ribose sugar conformational switch in the LTR-retrotransposon Ty3 polypurine
      tract-containing RNA/DNA hybrid.
AB  - To probe structural features of a polypurine tract (PPT) that mediate its
      specific recognition and processing, a model 20 bp RNA/DNA hybrid duplex, which
      includes the full PPT sequence of the Saccharomyces cerevisiae LTR
      retrotransposon Ty3, has been investigated using solution NMR spectroscopy. While
      homonuclear NOESY and DQF-COSY analyses indicate that this PPT-containing RNA/DNA
      hybrid adopts an overall A-form-like helical geometry, an unexpected sugar pucker
      switch has been detected for the ribose at position +1, relative to the cleavage
      site, on the RNA strand. A model of the conformational changes induced by the A-
      to B-type sugar pucker switch shows a significant change in the backbone
      trajectory of the RNA strand, which alters the presentation of backbone phosphate
      and 2' hydroxyl groups 3' of this residue. This observation implies that part of
      the mechanism governing RNase H fidelity may be through distortion of the RNA/DNA
      helix one base ahead of the scissile bond.

PMID- 16305192
TI  - Alpha,omega-distyryl oligothiophenes: high mobility semiconductors for
      environmentally stable organic thin film transistors.
AB  - Critical to the development of organic electronics is the design and synthesis of
      new organic semiconductors with improved electrical performance and enhanced
      environmental stability. We present in this communication the synthesis of a
      series of simple oligothiophene derivatives that bear the styryl unit as terminal
      substituent. Thin film field-effect transistors incorporating these compounds
      show high electrical performance, such as mobilities as high as 0.1 cm2/Vs, along
      with exceptional stability under ambient conditions. Especially, the longer
      oligomer, DS-4T, containing the quaterthiophene core gives rise to devices that
      show no decrease in performance after more than 17 months of storage and under
      continuous operation. Such stability features are unprecedented in the
      oligothiophene series.

PMID- 16305193
TI  - Using meta conjugation to enhance charge separation versus charge recombination
      in phenylacetylene donor-bridge-acceptor complexes.
AB  - A pair of donor-bridge-acceptor electron-transfer complexes, with a carbazole
      donor and a naphthalimide acceptor connected by either a para- or meta-conjugated
      phenylacetylene bridge, are synthesized and studied using time-resolved and
      steady-state spectroscopy. These experiments show that the charge separation
      times, which depend on the coupling of the donor and acceptor through the excited
      bridge moiety, are similar for the two molecules (Meta and Para). The charge
      recombination time, however, is a factor of 10 slower for Meta than for Para.
      These results are related to changes in the electronic coupling of the bridge
      depending on its electronic state, and show that meta-conjugated bridges provide
      a possible motif for the design of asymmetric molecular wires.

PMID- 16305194
TI  - Low-barrier hydrogen bond between phosphate and the amide group in
      phosphopeptide.
AB  - As the conversion between the monoionic (1) and diionic (2) form of the phosphate
      occurs, the phosphorylated peptides or proteins can not only cause the formation
      of a hydrogen bond between the phosphate group and the amide group but also
      change the strength of the hydrogen bond to form low-barrier hydrogen bonds
      (LBHBs). This reversible protonation of the phosphate group, which changes both
      the electrostatic properties of the phosphate group and the strength of the
      hydrogen bond, provides a possible mechanism in regulating protein function.

PMID- 16305195
TI  - A 3D canted antiferromagnetic porous metal-organic framework with anatase
      topology through assembly of an analogue of polyoxometalate.
AB  - The unique porous metal-organic framework {KCo3(C6H4O7)(C6H5O7)(H2O)2.8H2O}8 (1),
      which exhibits an unprecedented infinite 3D (3,6)-connected decorated anatase
      net, has been obtained by hydrothermal reaction. Upon dehydration, the compound
      retains crystallinity and exhibits a type I N2 sorption isotherm, characteristic
      of a microporous solid with apparent Langmuir surface area 939 m2/g and pore
      volume 0.31 cm3/g. Magnetic measurements for both 1 and dehydrated 1 show the
      spin-canted antiferromagnetic state below 5 K and a magnetic hysteresis loop at 2
      K. Thus, dehydrated 1 represents the first metal-organic framework for which
      microporosity and a spin-canted antiferromagnetic state coexist, which
      demonstrates that the self-assembly of organo-polymetal clusters and metal ions
      can provide a potential route to magnetic porous metal-organic frameworks.

PMID- 16305196
TI  - Porous BCN nanotubular fibers: growth and spatially resolved cathodoluminescence.
AB  - Porous boron carbonitride nanotubular fibers with BCN stoichiometry and
      homogeneous B, C, and N species distribution were fabricated via the CVD method.
      Spatially resolved cathodoluminescence measurements on individual nanostructures
      revealed intense ultraviolet emission centered at 319 nm, suggesting the
      characteristics of a semiconductor with a band gap of 3.89 eV. It is believed
      that the present nanostructures may have a variety of applications in ultraviolet
      optical devices, hydrogen storage systems, and field emission apparatus.

PMID- 16305197
TI  - Double direct templating of periodically nanostructured ZnS hollow microspheres.
AB  - We introduce a "double direct templating" method for obtaining hollow
      microspheres with periodically nanostructured walls. Silica or polystyrene
      colloids are dispersed in a self-assembled hexagonal lyotropic liquid crystal
      containing precursors for ZnS. The semiconductor ZnS mineralizes on the surface
      of the colloid, expressing a pore morphology that is a copy of the structure of
      the liquid crystal. After etching of the sacrificial colloids, hollow capsules
      with templated and uniform mesoporous shells are obtained.

PMID- 16305198
TI  - High charge-carrier mobility in an amorphous hexaazatrinaphthylene derivative.
AB  - An isomeric mixture of a tris(pentafluorobenzyl ester) derivative of
      hexaazatrinaphthylene forms stable amorphous films with an effective charge
      carrier mobility of 0.02 cm2/Vs, while the pure 2,8,15-isomer exhibits widely
      differing morphologies and carrier mobilities (0.001-0.07 cm2/Vs), depending
      critically on the processing conditions.

PMID- 16305199
TI  - Supramolecular photonic therapeutic agents.
AB  - A new approach to achieving selectivity for photodynamic therapy based upon the
      reversible off/on switching of the key therapeutic property (singlet oxygen
      generation) of a supramolecular photonic therapeutic agent (SPTA) in response to
      an external stimulus in the surrounding microenvironment is described. A series
      of SPTA analogues with pH responsive receptors of varying pKa are presented, in
      which the generation of singlet oxygen is shown to be dependent upon a proton
      source. For example, systems have been constructed such that the excited state
      energy of the photosensitizer can be decayed by a rapid photoinduced electron
      transfer (PET) mechanism, resulting in virtually no singlet oxygen being
      generated, but when the amine receptor is protonated the PET mechanism does not
      operate and singlet oxygen is produced. In vitro efficacy demonstrated that the
      SPTA derivatives can be activated within cells and one analogue is measured to
      have an EC50 value of 5.8 nM when assayed in the MRC5 cell line.

PMID- 16305200
TI  - A metal-organic framework functionalized with free carboxylic acid sites and its
      selective binding of a Cl(H2O)4(-) cluster.
AB  - A metal-organic framework with one-dimensional channels decorated with -COOH
      binding sites was synthesized under aqueous acidic conditions, which inhibited
      the participation of these groups to metal coordination or self-association by
      hydrogen bonding. This material selectively includes Cl(H2O)4- clusters in its
      channels, as revealed by single-crystal X-ray diffraction analysis, which
      represents the first structural characterization of such a water-chloride
      cluster.

PMID- 16305201
TI  - Selective anion encapsulation by a metalated cryptophane with a pi-acidic
      interior.
AB  - Metalation of the exterior arene faces of the molecular capsule (+/-)-cryptophane
      E with [Cp*Ru]+ moieties results in a pi-acidic cavity capable of encapsulating
      anions. The [CF3SO3]- and [SbF6]- salts have been crystallographically
      characterized and demonstrate the encapsulation of these anions by the metalated
      cryptophane. 1H and 19F NMR spectroscopy establish the binding of anions in
      NO2CD3 solution and reveal the relative affinity of the cavity for different
      anions (KX-/KOTf-): [BF4]- approximately 0, [PF6]- = 1.18, [CF3SO3]- identical
      with 1, [SbF6]- = 0.30. Variable temperature rate studies reveal the activation
      barrier for triflate encapsulation to be DeltaG298K = 18.0(8) kcal.mol-1 (DeltaH
      = 17.5(4) kcal.mol-1 and DeltaS = 2(1) cal.mol-1.K-1).

PMID- 16305202
TI  - Silylmethyl-substituted aziridine and azetidine as masked 1,3- and 1,4-dipoles
      for formal [3 + 2] and [4 + 2] cycloaddition reactions.
AB  - 2-tert-Butyldiphenylsilylmethyl-substituted aziridine and the corresponding
      azetidine reacted efficiently with nitriles and carbonyl substrates to generate
      imidazoline, oxazolidine, and tetrahydropyrimidine products. The azetidine
      rearranged efficiently to the pyrrolidine skeleton involving migration of silicon
      under BF3.Et2O conditions. The tert-butyldiphenylsilylmethyl function, latent to
      CH2OH group, controlled not only the regioselectivity of aziridine and azetidine
      cleavage but also the relative stereochemistry of the substituents in the
      products derived from substituted aziridine.

PMID- 16305203
TI  - Reaction products with internal energy beyond the kinematic limit result from
      trajectories far from the minimum energy path: an example from H + HBr --> H2 +
      Br.
AB  - The importance of reactive trajectories straying far from the minimum energy path
      is demonstrated for the bimolecular reaction H + HBr --> H2(v', j') + Br at 53
      kcal/mol collision energy. Product quantum state distributions are measured and
      calculated using the quasi-classical trajectory technique, and the calculations
      indicate that highly internally excited H2 products result from indirect reactive
      trajectories with bent transition states. A general argument is made suggesting
      that reaction products with internal energy exceeding a kinematic constraint can,
      in general, be attributed to reactive collisions straying far from the minimum
      energy path.

PMID- 16305204
TI  - Preorganization in highly enantioselective diaza-Cope rearrangement reaction.
AB  - Crystal structure and activation entropy data indicate that H-bond directed diaza
      Cope rearrangement of chiral diimines takes place with a high degree of
      preorganization. CD spectroscopy and HPLC data show that there is inversion of
      stereochemistry for the reaction with excellent enantioselectivity.

PMID- 16305205
TI  - A low-molecular-mass gelator with an electroactive tetrathiafulvalene group:
      tuning the gel formation by charge-transfer interaction and oxidation.
AB  - A new low-molecular-mass gelator with one TTF and one urea group is described. It
      was found that the gel formation can be tuned by formation of CT complexes and
      oxidation.

PMID- 16305206
TI  - Solvent polarization and kinetic isotope effects in nitroethane deprotonation and
      implications to the nitroalkane oxidase reaction.
AB  - We have carried out a mixed molecular dynamics and centroid path integral
      simulation using a combined quantum mechanical and molecular mechanical (QM/MM)
      potential to study the anomalous Bronsted relationship between rates and
      equilibria for deprotonation of nitroalkanes in water, which is known as the
      nitroalkane anomaly. The deprotonation process is catalyzed by nitroalkane
      oxidase. Our results show that the difference in solvent polarization effects for
      the TS and products is a major factor for the differential solvent effects on
      rate and equilibrium of nitroalkane deprotonation. This is due to poor charge
      delocalization as a result of slow rehybridization compared to bond breaking.
      Although solvent effects do not affect significantly the computed kinetic isotope
      effects in comparison with the gas-phase value, there is slight solvent-induced
      increase in tunneling. The present results suggest that an effective means by
      which the transition state can be stabilized in the enzyme nitroalkane oxidase is
      to facilitate the Calpha rehybridization.

PMID- 16305207
TI  - Large-scale Ni-doped ZnO nanowire arrays and electrical and optical properties.
AB  - Large-scale Ni-doped ZnO nanowire (NW) arrays are grown. The electrical
      conductivity of a single Ni-doped ZnO NW has been increased for 30 times. The
      photoluminescence (PL) spectrum of the doped ZnO NWs has a red shift, suggesting
      possible doping induced band edge bending. The doped NW arrays could be the basis
      for building integrated nanoscale transistors, sensors, and photodetectors.

PMID- 16305208
TI  - Catalytic asymmetric deprotonation using a ligand exchange approach.
AB  - A novel ligand exchange approach to catalytic asymmetric deprotonation
      electrophilic trapping has been developed that uses 1.3 equiv of s-BuLi, 0.06-0.2
      equiv of chiral diamine ((-)-sparteine or a (+)-sparteine surrogate), and 1.2
      equiv of achiral bispidine. The methodology is illustrated with a range of
      examples and gives access to either enantiomer of useful chiral products in good
      yields using substoichiometric amounts of chiral diamines.

PMID- 16305209
TI  - Catechol oxidase activity of di-Cu2+-substituted aminopeptidase from Streptomyces
      griseus.
AB  - Streptomyces griseus aminopeptidase exhibits activities toward the hydrolyses of
      peptides and bis(p-nitrophenyl)phosphate (40 billion fold) and catechol oxidation
      reported herein with catalytic efficiency (kcat/Km) only about 10 times smaller
      than that of gypsywort catechol oxidase. The multifunctionality of this enzyme
      suggests that it is a unique system for further exploration of protein structure
      and function and a template for design of enzymes of diverse activities.

PMID- 16305210
TI  - A capping methodology for the synthesis of lower mu-oxo-phthalocyaninato silicon
      oligomers.
AB  - A mixed condensation of a substituted and unsubstituted silicon phthalocyanine
      monomer, in which the former serves as a "cap" to a growing oligomeric chain,
      provides unprecedented access to a mixed dimer, trimers, and a tetramer. An
      important element of product control can be achieved by changing the ratio of the
      precursor monomers.

PMID- 16305211
TI  - Effect of core size on the partition of organic solutes in the monolayer of water
      soluble nanoparticles: an ESR investigation.
AB  - ESR spectroscopy has been used to study the interaction of para-pentylbenzyl
      hydroxyalkyl nitroxide with the monolayer of water-soluble protected gold
      clusters having a core diameter ranging from 1.6 to 5.3 nm. The solubilization of
      the nitroxide probe in the more hydrophobic environment of the monolayer strongly
      depends on the size of the gold core. In particular, the partition equilibrium
      constant increases as the nanoparticle diameter decreases. These results have
      been attributed to the different packing of the chains in the monolayer resulting
      from the different radius of curvature of the investigated nanoparticles. This
      represents, to the best of our knowledge, the first report demonstrating that the
      core size of metallic nanoparticles affects the solvating properties of the
      protective organic monolayer.

PMID- 16305212
TI  - Highly enantioselective Biginelli reaction using a new chiral ytterbium catalyst:
      asymmetric synthesis of dihydropyrimidines.
AB  - The highly enantioselective three-component Biginelli condensation catalyzed by a
      recyclable chiral ytterbium triflate with a novel hexadentate amine phenol ligand
      containing a pyridyl group has been developed. A wide range of optically active
      dihydropyrimidines with remarkable pharmacological interest was obtained in high
      yields with good to excellent enantioselectivities under mild conditions.

PMID- 16305213
TI  - Tertiary contact formation in alpha-synuclein probed by electron transfer.
AB  - To explore tertiary contact formation in alpha-synuclein, a natively unfolded
      protein implicated in Parkinson's disease, we have measured the rates of reaction
      between a powerful electron donor, the tryptophan (W) triplet excited state, and
      an acceptor, 3-nitro-tyrosine (Y(NO2)) in six different variants, probing loop
      sizes between 15 and 132 residues. Electron transfer rates decrease with loop
      size with the fastest contact time of 140 ns for the N-terminal pair and the
      slowest of 1.2 mus for the N- to C-terminal pair. Diffusion coefficients ranging
      from approximately 2 x 10-6 to approximately 10-5 cm2 s-1 were extracted from
      simultaneous fits of the W to Y(NO2) electron (triplet excited state) and energy
      transfer (singlet excited state) kinetics.

PMID- 16305214
TI  - Dynamical arrest of electron transfer reorganization in super-cooled water.
AB  - This paper reports the results of Molecular Dynamics (MD) simulations of the
      solvent reorganization energy of electron transfer (ET) reactions in low
      temperature solvents. Simulations are carried out for a model charge-transfer
      optical dye (p-nitroaniline) in SPC/E water in a range of temperatures down to
      the point of solvent ideal glass transition. We show a significant departure of
      the solvent reorganization energy, measured on a given time window, from its
      thermodynamic limit obtained by averaging over long simulation trajectories. Our
      results thus indicate that optical solvatochromism and activation parameters of
      ET reactions measured in viscous solvents will be significantly affected by the
      dynamical arrest of nuclear solvation when the experimental time scale becomes
      comparable to the characteristic relaxation time of the solvent.

PMID- 16305215
TI  - Monodisperse protein-based glycopolymers via a combined biosynthetic and chemical
      approach.
AB  - Helical protein polymers with sequences comprising primarily alanine and
      glutamine have been designed to contain glutamic acid residues at distances that
      are targeted to match the receptor spacing of certain toxins and lectins. These
      proteins are readily expressed and purified from E. coli and are highly helical
      under a variety of solution conditions. The helical artificial proteins are also
      competent for chemical modification with saccharides for inhibition of select
      bacterial toxins and lectins. In the investigations reported here, multivalent
      artificial glycoproteins bearing galactose moieties as pendant groups have been
      prepared via the coupling reaction of amine-functionalized galactose with the
      glutamic acid functional groups of the protein polymer. Glycosylation of proteins
      was confirmed via mass spectrometry, NMR spectroscopy, SDS-PAGE, and photometric
      methods. CD spectroscopy shows that the resulting glycosylated proteins maintain
      a highly helical structure, and competitive ELISA assays suggest the efficient
      binding of these glycoproteins to cholera toxin. These results demonstrate that
      the integration of biological and chemical approaches in the synthesis of well
      defined polymeric structures offers significant opportunities in the purposeful
      design of glycopolymers for applications in biology.

PMID- 16305216
TI  - Highly enantioselective copper(I)-fesulphos-catalyzed 1,3-dipolar cycloaddition
      of azomethine ylides.
AB  - The catalyst system formed by Cu(CH3CN)4ClO4 and the planar chiral P,S-ligand
      Fesulphos behaves as a very efficient chiral Lewis acid in the catalytic
      asymmetric 1,3-dipolar cycloaddition of azomethine ylides. This catalyst shows a
      remarkable reactivity at low catalyst loading (0.5-3 mol %), affording in good
      yields the endo adducts with exceptional levels of enantioselectivity (up to >99%
      ee). This catalytic asymmetric procedure has a broad structural scope with regard
      to both azomethine and dipolarophile substitution. The first examples of
      catalytic asymmetric 1,3-dipolar cycloaddition with ketimine-derived azomethines
      are reported.

PMID- 16305217
TI  - Direct synthesis of mesoporous titania particles having a crystalline wall.
AB  - In this study, we demonstrate a novel method for preparing crystallized
      mesoporous titania by using a low-temperature synthesis technique in the presence
      of cationic surfactant. XRD patterns showed that the titania particles obtained
      had both hexagonal structure and a wall with anatase crystalline structure.
      Transmission electron microscopy (TEM) observation and corresponding electron
      diffraction pattern confirmed that the calcined particles are crystallized
      mesoporous titania.

PMID- 16305218
TI  - Size-controlled synthesis of near-monodisperse gold nanoparticles in the 1-4 nm
      range using polymeric stabilizers.
AB  - We report here a simple one-step protocol for the preparation of near
      monodisperse gold hydrosols in the small size regime (<5 nm). The particle size
      can be controlled by varying the concentration of the stabilizing polymer, which
      can be readily displaced by thiol ligands to yield monolayer protected clusters
      of the usual type.

PMID- 16305219
TI  - A bimetallic complex containing a cyclopentadienyl-annulated imidazol-2-ylidene.
AB  - A bimetallic carbene complex architecture that incorporates a cyclopentadienyl
      annulated imidazol-2-ylidene moiety is characterized. The ligand architecture
      enables direct electronic interaction between the pi- and sigma-bonded metals. A
      preliminary example of aqueous Suzuki coupling employing a metallocene-fused
      imidazol-2-ylidene-derived catalyst is described.

PMID- 16305220
TI  - Unfolding of heptameric co-chaperonin protein follows "fly casting" mechanism:
      observation of transient nonnative heptamer.
AB  - Protein recognition and binding play a fundamental role in living systems but
      sometimes also result in pathological aggregates. To probe the coupling between
      folding and binding in a homoheptameric system, we have characterized the time
      resolved unfolding/disassembly mechanism of human co-chaperonin protein 10
      (cpn10) by a combination of experimental and computational methods. The results
      from both approaches are in excellent agreement and make obvious that the kinetic
      process is three-state: an initial polypeptide-unfolding step, resulting in a non
      native heptamer, is followed by a slower heptamer-dissociation step. This
      demonstrates that the barriers on the kinetic free-energy landscape are defined
      by thermodynamic stability. cpn10 is one of few, and the only heptameric,
      experimentally characterized system that follows the "fly casting scenario" of
      molecular recognition.

PMID- 16305221
TI  - An electric cyclophane: cavity control based on the rotation of a paraphenylene
      by redox switching.
AB  - Although a free rotation around a single bond gives no mechanical output, it has
      let us imagine a molecular motor. A para-substituted aromatic ring can be
      regarded as a rotator with the para-rotation axis. When it is incorporated in a
      wider pi-conjugated system, a quinoidal structure is generated accompanied by
      oxidation on the substituted groups at the 1,4-position, and the axis is fixed. A
      paraphenylenediamine was selected as the nanomechanical molecular module capable
      of locking and releasing the free rotation using an electrode in solution. We
      inserted the module into a simple molecular system, cyclophane. It was clarified
      that the cyclophane was able to open and close its cavity in a reversible redox
      process repeatedly.

PMID- 16305222
TI  - Enantioselective protonation of catalytically generated chiral enolates as an
      approach to the synthesis of alpha-chloroesters.
AB  - Treatment of alpha,alpha-dichloroaldehydes with various phenols in the presence
      of chiral triazolium salt catalysts and excess base results in the synthesis of
      alpha-chloro aryl esters in good yield and enantioselectivity. The reaction is
      tolerant of various functionality on the aldehyde as well as several
      electronically diverse phenols. The product chloroesters were further transformed
      into chloroacid, chlorohydrin, and azidoesters with nearly complete retention of
      enantioselectivity.

PMID- 16305223
TI  - anti-selective direct asymmetric Mannich reactions catalyzed by axially chiral
      amino sulfonamide as an organocatalyst.
AB  - A direct asymmetric Mannich reaction using a novel axially chiral amino
      trifluoromethanesulfonamide (S)-3 has been developed in highly anti-selective and
      enantioselective manners. Thus, in the presence of a catalytic amount of (S)-3,
      the reactions between aldehydes and the alpha-imino ester 4 proceed smoothly to
      give the functional beta-amino aldehydes with significantly higher anti/syn ratio
      and enantioselectivity than previously possible.

PMID- 16305224
TI  - Cationic palladium-catalyzed hydrosilylative cross-coupling of alkynes with
      alkenes.
AB  - A cationic palladium complex-catalyzed cross-coupling of alkynes with alkenes is
      presented, which occurs selectively under the hydrosilylation conditions using
      trichlorosilane. The unique reaction might be well understood in terms of an
      initial hydropalladation of a given 1-alkyne to form regioselectively a 1
      alkenylpalladium species, which, in turn, undergoes easily and specifically an
      alkene insertion. The resulting homoallylic organopalladium species terminates
      one catalytic cycle by substituting the palladium center with a trichlorosilyl
      group to give product(s).

PMID- 16305225
TI  - L-canavanine is a time-controlled mechanism-based inhibitor of Pseudomonas
      aeruginosa arginine deiminase.
AB  - The mechanism for inhibition of the Pseudomonas aeruginosa arginine deiminase
      (PaADI) by the arginine analogue l-canavanine was investigated. Inhibition by
      this substance (kinact = 0.31 +/- 0.03 min-1 and Ki = 1.7 +/- 0.5 mM) is
      associated with the formation of a modestly stable S-alkylthiouronium
      intermediate, detected by using kinetic techniques and identified by using
      electrospray ionization mass spectrometry. The electronic and/or orientation
      effects, caused by oxygen-for-methylene substitution in l-canavanine, on the rate
      of enzyme regeneration from the S-alkylthiouronium intermediate could serve as
      the basis for a strategy for the rational design of new slow substrate inhibitors
      of ADI.

PMID- 16305226
TI  - Intrinsic isotope effects on benzylic hydroxylation by the aromatic amino acid
      hydroxylases: evidence for hydrogen tunneling, coupled motion, and similar
      reactivities.
AB  - Deuterium kinetic isotope effects for hydroxylation of the methyl group of 4
      methylphenylalanine have been used as a probe of the relative reactivities of the
      hydroxylating intermediates in the aromatic amino acid hydroxylases
      phenylalanine, tyrosine, and tryptophan hydroxylase. When there are three
      deuterium atoms in the methyl group, all three enzymes exhibit an intrinsic
      isotope effect of about 13. The temperature dependence of the isotope effect is
      consistent with moderate tunneling, with the extent of tunneling identical for
      all three enzymes. In the case of phenylalanine hydroxylase, the presence of the
      regulatory domain has no effect on the values. The intrinsic primary and
      secondary isotope effects were determined using 4-methylphenylalanine containing
      one or two deuterium atoms in the methyl group. With one deuterium atom, the
      intrinsic primary and secondary effects have average values of 10 and 1.1,
      respectively. With two deuterium atoms, the primary effects decrease to 7.4 and
      the secondary effect increases to 1.3, consistent with coupled motion of the
      primary and secondary hydrogens. The results with all three enzymes are
      consistent with a hydrogen abstraction mechanism. The similarities of the isotope
      effects and extent of tunneling establish that the reactivities of the
      hydroxylating intermediates in the three enzymes are essentially identical.

PMID- 16305227
TI  - A green chemistry approach to a more efficient asymmetric catalyst: solvent-free
      and highly concentrated alkyl additions to ketones.
AB  - There is a great demand for development of catalyst systems that are not only
      efficient and highly enantioselective but are also environmentally benign. Herein
      we report investigations into the catalytic asymmetric addition of alkyl and
      functionalized alkyl groups to ketones under highly concentrated and solvent-free
      conditions. In comparison with standard reaction conditions employing toluene and
      hexanes, the solvent-free and highly concentrated conditions permit reduction in
      catalyst loading by a factor of 2- to 40-fold. These new conditions are general
      and applicable to a variety of ketones and dialkylzinc reagents to provide
      diverse tertiary alcohols with high enantioselectivities. Using cyclic conjugated
      enones, we have performed a tandem asymmetric addition/diastereoselective
      epoxidation using the solvent-free addition conditions followed by introduction
      of a 5.5 M decane solution of tert-butyl hydroperoxide (TBHP) to generate epoxy
      alcohols. This one-pot procedure allows access to syn epoxy alcohols with three
      contiguous stereocenters with excellent enantio- and diastereoselectivities and
      high yields. Both the solvent-free asymmetric additions and asymmetric
      addition/diastereoselective epoxidation reactions have been conducted on larger
      scale (5 g substrate) with 0.5 mol % catalyst loadings. In these procedures,
      enantioselectivities equal to or better than 92% were obtained with isolated
      yields of 90%. The solvent-free and highly concentrated conditions are a
      significant improvement over previous solvent-based protocols. Further, this
      chemistry represents a rare example of a catalytic asymmetric reaction that is
      highly enantioselective under more environmentally friendly solvent-free
      conditions.

PMID- 16305228
TI  - Structural and spectroscopic demonstration of agostic C-C interactions in
      electron-deficient metallacyclobutanes and related cage complexes: possible
      implications for olefin polymerizations and metatheses.
AB  - The reaction of the half-open titanocene, Ti(C5H5)(c-C8H11)(PMe3) (c-C8H11 =
      cyclooctadienyl), with two equivalents of PhC2SiMe3 leads to their incorporation
      and coupling to the dienyl fragment. One alkyne inserts into a C-H bond of the
      central CH2 group of the c-C8H11 ligand's edge-bridge, while the second undergoes
      a 5+2 coupling with the dienyl fragment, yielding coordinated sigma-allyl and
      olefin fragments, as demonstrated by X-ray diffraction. Together with the C5H5
      and PMe3 coordinations, this leads to a 14-electron count. While the very
      electron-deficient titanium center passes up potential pi coordination of the
      allyl fragment, it instead engages in interactions with one or two C-C bonds, and
      perhaps a C-H bond, as revealed from the structural and spectroscopic data.
      Similar interactions have been found in electron-deficient metallacyclobutane
      complexes of titanium and zirconium, but not in the 18-electron molybdenum and
      tungsten analogues. These and other observations may have implications relating
      to metatheses and polymerizations of olefins.

PMID- 16305229
TI  - Fe3+-hydroxide ligation in the superoxide reductase from Desulfoarculus baarsii
      is associated with pH dependent spectral changes.
AB  - Superoxide reductase (SOR) catalyzes the reduction of O2*- to H2O2. Its active
      site consists of a non-heme Fe2+ center in an unusual square-pyramidal [His4 Cys]
      coordination. Like many SORs, the electronic absorption band corresponding to the
      oxidized active site of the SOR from Desulfoarculus baarsii exhibits a pH
      dependent alkaline transition changing from ca. 644 to 560 nm as the pH increases
      and with an apparent pKa of 9.0. Variants in which the conserved amino acids
      glutamate 47 and lysine 48 were replaced by the neutral residues alanine (E47A)
      and isoleucine (K48I), respectively, exhibited the same alkaline transition but
      at lower apparent pKa values of 6.7 and 7.6, respectively. Previous work
      [Niviere, V.; Asso, M.; Weill, C. O.; Lombard, M.; Guigliarelli, B.; Favaudon,
      V.; Houee-Levin, C. Biochemistry 2004, 43, 808-818] has shown that this alkaline
      transition is associated with the protonation/deprotonation of an unidentified
      base, B-, which is neither E47 nor K48. In this work, we show by resonance Raman
      spectroscopy that at basic pH a high-spin Fe3+-OH species is formed at the active
      site. The presence of the HO- ligand was directly associated with an absorption
      band maximum at 560 nm, whereas upon protonation, the band shifts to 644 nm. With
      respect to our previous work, B- can be identified with this high-spin Fe3+-OH
      species, which upon protonation results in a water molecule at the active site.
      Implications for the SOR catalytic cycle are proposed.

PMID- 16305230
TI  - Cloning, sequencing, analysis, and heterologous expression of the fredericamycin
      biosynthetic gene cluster from Streptomyces griseus.
AB  - Fredericamycin (FDM) A, a pentadecaketide featuring two sets of peri-hydroxy
      tricyclic aromatic moieties connected through a unique chiral spiro carbon
      center, exhibits potent cytotoxicity and has been studied as a new type of
      anticancer drug lead because of its novel molecular architecture. The fdm gene
      cluster was localized to 33-kb DNA segment of Streptomyces griseus ATCC 49344,
      and its involvement in FDM A biosynthesis was proven by gene inactivation,
      complementation, and heterologous expression experiments. The fdm cluster
      consists of 28 open reading frames (ORFs), encoding a type II polyketide synthase
      (PKS) and tailoring enzymes as well as several regulatory and resistance
      proteins. The FDM PKS features a KSalpha subunit with heretofore unseen tandem
      cysteines at its active site, a KSbeta subunit that is distinct phylogenetically
      from KSbeta of hexa-, octa-, or decaketide PKSs, and a dedicated
      phosphopantetheinyl transferase. Further study of the FDM PKS could provide new
      insight into how a type II PKS controls chain length in aromatic polyketide
      biosynthesis. The availability of the fdm genes, in vivo characterization of the
      fdm cluster in S. griseus, and heterologous expression of the fdm cluster in
      Streptomyces albus set the stage to investigate FDM A biosynthesis and engineer
      the FDM biosynthetic machinery for the production of novel FDM A analogues.

PMID- 16305231
TI  - Reduction potential tuning at a type 1 copper site does not compromise electron
      transfer reactivity.
AB  - Type 1 (T1) copper sites promote biological electron transfer (ET) and typically
      possess a weakly coordinated thioether sulfur from an axial Met [Cu(II)-Sdelta
      approximately 2.6 to 3.3 A] along with the conserved His2Cys equatorial ligands.
      A strong axial bond [Cu(II)-Oepsilon1 approximately 2.2 A] is sometimes provided
      by a Gln (as in the stellacyanins), and the axial ligand can be absent (a Val,
      Leu or Phe in the axial position) as in ceruloplasmin, Fet3p, fungal laccases and
      some plantacyanins (PLTs). Cucumber basic protein (CBP) is a PLT which has a
      relatively short Cu(II)-S(Met89) axial bond (2.6 A). The Met89Gln variant of CBP
      has an electron self-exchange (ESE) rate constant (k(ese), a measure of intrinsic
      ET reactivity) approximately 7 times lower than that of the wild-type protein.
      The Met89Val mutation to CBP results in a 2-fold increase in k(ese). As the axial
      interaction decreases from strong Oepsilon1 of Gln to relatively weak Sdelta of
      Met to no ligand (Val), ESE reactivity is therefore enhanced by approximately 1
      order of magnitude while the reduction potential increases by approximately 350
      mV. The variable coordination position at this ubiquitous ET site provides a
      mechanism for tuning the driving force to optimize ET with the correct partner
      without significantly compromising intrinsic reactivity. The enhanced reactivity
      of a three-coordinate T1 copper site will facilitate intramolecular ET in fungal
      laccases and Fet3p.

PMID- 16305232
TI  - Thermodynamics of rhodium hydride reactions with CO, aldehydes, and olefins in
      water: organo-rhodium porphyrin bond dissociation free energies.
AB  - Tetra(p-sulfonato-phenyl) porphyrin rhodium hydride ([(TSPP)Rh-D(D2O)](-4)) (1)
      reacts in water (D2O) with carbon monoxide, aldehydes, and olefins to produce
      metallo formyl, alpha-hydroxyalkyl, and alkyl complexes, respectively. The
      hydride complex (1) functions as a weak acid in D2O and partially dissociates
      into a rhodium(I) complex ([(TSPP)Rh(I)(D2O)](-5)) and a proton (D+). Fast
      substrate reactions of 1 in D2O compared to reactions of rhodium porphyrin
      hydride ((por)Rh-H) in benzene are ascribed to aqueous media promoting formation
      of ions and supporting ionic reaction pathways. The regioselectivity for addition
      of 1 to olefins is predominantly anti-Markovnikov in acidic D2O and exclusively
      anti-Markovnikov in basic D2O. The range of accessible equilibrium thermodynamic
      measurements for rhodium hydride substrate reactions is substantially increased
      in water compared to that in organic media through exploiting the hydrogen ion
      dependence for the equilibrium distribution of species in aqueous media.
      Thermodynamic measurements are reported for reactions of a rhodium porphyrin
      hydride in water with each of the substrates, including CO, H2CO, CH3CHO,
      CH2=CH2, and sets of aldehydes and olefins. Reactions of rhodium porphyrin
      hydrides with CO and aldehydes have nearly equal free-energy changes in water and
      benzene, but alkene reactions that form hydrophobic alkyl groups are
      substantially less favorable in water than in benzene. Bond dissociation free
      energies in water are derived from thermodynamic results for (TSPP)Rh-organo
      complexes in aqueous solution for Rh-CDO, Rh-CH(R)OD, and Rh-CH2CH(D)R units and
      are compared with related values determined in benzene.

PMID- 16305234
TI  - A bisphosphonate monoamide analogue of DOTA: a potential agent for bone
      targeting.
AB  - A new macrocyclic DOTA-like ligand (BPAMD) for bone imaging and therapy
      containing a monoamide bis(phosphonic acid) bone-seeking group was designed and
      synthesized. Its lanthanide(III) complexes were prepared and characterized by 1H
      and 31P NMR spectroscopy. The Gd(III)-BPAMD complex was investigated in detail by
      1H and 17O relaxometric studies to inspect parameters relevant for its potential
      application as an MRI contrast agent. Sorption experiments were conducted with
      Gd(III) and Tb(III) complexes using hydroxyapatite (HA) as a model of bone
      surface. Very effective uptake of the Gd-BPAMD complex by the HA surface was
      observed in NMR experiments. Radiochemical studies with the (160Tb-BPAMD)-HA
      system proved the sorption to be remarkably fast and strong on one hand and fully
      reversible on the other hand. The strong (Gd-BPAMD)-HA interaction was also
      supported by 1H NMRD measurements in the presence of a hydroxyapatite slurry,
      which showed an increase of the rotational correlation time upon adsorption of
      the complex on the HA surface, resulting in a significant relaxivity enhancement.
      The amide-bis(phosphonate) moiety is the only factor responsible for the binding
      of the complex to HA.

PMID- 16305235
TI  - pH-responsive copolymer films by surface-catalyzed growth.
AB  - We have engineered a new class of pH-responsive polymer films on gold surfaces by
      first developing a controlled, surface-catalyzed polymerization to prepare a
      copolymer film consistent with poly(methylene-co-ethyl acetate) and subsequently
      hydrolyzing the ester side chains to varying extents to yield carboxylic acids
      (denoted as PM-CO2H). When pH is increased, the acid groups become deprotonated
      or charged, dramatically increasing their water solubility and greatly altering
      the film properties. The carboxylic acid content within the copolymer film can be
      adjusted by changing the monomer concentration ratio used in the polymerization
      process or the length of time for the hydrolysis. We have designed PM-CO2H films
      to consist predominately (>95%) of polymethylene (PM) so that the film is
      hydrophobic in the uncharged state and, thereby, exhibits an extremely large pH
      induced response in barrier properties once ionized. The effect of polymer
      composition on pH response was investigated by electrochemical impedance
      spectroscopy (EIS), reflectance-absorption infrared spectroscopy (RAIRS), and
      contact angle measurements. At a 1%-4% molar acid content, the copolymer film
      exhibits a 5 orders of magnitude change in its resistance to ion transport over 2
      3 pH units. The pH at which this response begins can be tailored from pH 5 to pH
      10 by decreasing the acid content in the film from 4% to 1%.

PMID- 16305233
TI  - Palladium-catalyzed synthesis of 2,1'-disubstituted tetrahydrofurans from gamma
      hydroxy internal alkenes. Evidence for alkene insertion into a Pd-O bond and
      stereochemical scrambling via beta-hydride elimination.
AB  - Palladium-catalyzed reactions of gamma-hydroxy internal acyclic alkenes with aryl
      bromides afford 2,1'-disubstituted tetrahydrofurans in good yields with
      diastereoselectivities of 3-5:1. The analogous transformations of substrates
      bearing internal cyclic alkenes afford fused bicyclic and spirocyclic
      tetrahydrofuran derivatives in good yields with excellent diastereoselectivities
      (>20:1). A series of deuterium labeling experiments indicate that the origin of
      the modest diastereoselectivity in reactions of acyclic internal alkene
      substrates likely derives from a series of reversible beta-hydride elimination
      and sigma-bond rotation processes that occur following a rare intramolecular
      alkene syn-insertion into an intermediate Pd(Ar)(OR) complex. In addition, these
      studies shed light on the chemoselectivity of insertion, suggesting that the
      alkene inserts into the Pd-O bond in preference to the Pd-C bond.

PMID- 16305236
TI  - The electron density of bridging hydrides observed via experimental and
      theoretical investigations on [Cr2(mu2-H)(Co)10]-.
AB  - The accurate experimental electron density distribution of [Cr2(mu2-H)(CO)10]-
      has been determined through X-ray diffraction at T = 28 K and gas phase
      theoretical calculations. The nature of the Cr-H-Cr bond has been investigated by
      means of the quantum theory of atoms in molecules, including the analysis of the
      Fermi hole distribution and the delocalization indicators from the pair density
      distribution. We were able to clarify not only the delocalization mechanism
      inside the three-center system but also the unexpected role of the equatorial
      carbonyls. In addition, the comparative study of a few Cr-H-X three center
      interactions has provided more insight into the nature of the M-H-M bond itself
      and has shed light on its peculiar stereochemical flexibility.

PMID- 16305237
TI  - Comparisons of NMR spectral quality and success in crystallization demonstrate
      that NMR and X-ray crystallography are complementary methods for small protein
      structure determination.
AB  - X-ray crystallography and NMR spectroscopy provide the only sources of
      experimental data from which protein structures can be analyzed at high or even
      atomic resolution. The degree to which these methods complement each other as
      sources of structural knowledge is a matter of debate; it is often proposed that
      small proteins yielding high quality, readily analyzed NMR spectra are a subset
      of those that readily yield strongly diffracting crystals. We have examined the
      correlation between NMR spectral quality and success in structure determination
      by X-ray crystallography for 159 prokaryotic and eukaryotic proteins, prescreened
      to avoid proteins providing polydisperse and/or aggregated samples. This study
      demonstrates that, across this protein sample set, the quality of a protein's
      [15N-1H]-heteronuclear correlation (HSQC) spectrum recorded under conditions
      generally suitable for 3D structure determination by NMR, a key predictor of the
      ability to determine a structure by NMR, is not correlated with successful
      crystallization and structure determination by X-ray crystallography. These
      results, together with similar results of an independent study presented in the
      accompanying paper (Yee, et al., J. Am. Chem. Soc., accompanying paper),
      demonstrate that X-ray crystallography and NMR often provide complementary
      sources of structural data and that both methods are required in order to
      optimize success for as many targets as possible in large-scale structural
      proteomics efforts.

PMID- 16305238
TI  - NMR and X-ray crystallography, complementary tools in structural proteomics of
      small proteins.
AB  - NMR spectroscopy and X-ray crystallography, the two primary experimental methods
      for protein structure determination at high resolution, have different advantages
      and disadvantages in terms of sample preparation and data collection and
      analysis. It is therefore of interest to assess their complementarity when
      applied to small proteins. Structural genomics/proteomics projects provide an
      ideal opportunity to make such comparisons as they generate data in a systematic
      manner for large enough numbers of proteins to allow firm conclusions to be
      drawn. Here we report a comparison for 263 unique proteins screened by both NMR
      spectroscopy and X-ray crystallography in our structural proteomics pipeline.
      Only 21 targets (8%) were deemed amenable to both methods based on an initial 2D
      15N-HSQC NMR spectrum and optimized crystallization trials. However, the use of
      both methods in the pipeline increased the total number of targets amenable to
      structure determination to 107, with 43 amenable to NMR only and 43 amenable to X
      ray crystallographic methods only. We did not observe a correlation between 15N
      HSQC spectral quality and the success of the same protein in crystallization
      screens. Similar results were found for an independent set of 159 proteins as
      reported in the accompanying paper by Snyder et al. Thus, we conclude that both
      methods are highly complementary, and in order to increase the number of proteins
      suited for structure determination, we suggest that both methods be used in
      parallel in screening of all small proteins for structure determination.

PMID- 16305239
TI  - Interconversions of aryl radicals by 1,4-shifts of hydrogen atoms. A synthesis of
      benzo[a]corannulene.
AB  - Aryl radicals generated ortho to aryl substituents by flash vacuum pyrolysis
      (FVP) of the corresponding aryl chlorides are shown to be capable of transferring
      hydrogen atoms between the ortho and ortho' positions (1,4-shifts of hydrogen
      atoms). In the examples described here, the rearranged aryl radicals are trapped
      by subsequent radical cyclization reactions. For example, FVP of 2-(o
      chlorophenyl)benzo[c]phenanthrene gives 1-phenylbenzo[ghi]fluoranthene as the
      major product by homolysis of the C-Cl bond, 1,4-shift of a hydrogen atom out of
      the sterically congested cove region to the radical center, cyclization of the
      rearranged radical, and rearomatization of the molecule by loss of the other cove
      region hydrogen. In a control experiment run under the same conditions, FVP of 2
      phenylbenzo[c]phenanthrene, which lacks a radical precursor, gave primarily
      recovered starting material. When the FVP was repeated using 2-(2,6
      dichlorophenyl)benzo[c]phenanthrene as the starting material, benzo[a]corannulene
      was obtained as the major product, presumably by the same cascade of events to
      produce 1-(o-chlorophenyl)benzo[ghi]fluoranthene, which then suffers a second
      radical cyclization spontaneously under the high-temperature conditions to give
      the geodesic polyarene.

PMID- 16305240
TI  - Co-C bond activation in methylmalonyl-CoA mutase by stabilization of the post
      homolysis product Co2+ cobalamin.
AB  - Despite decades of research, the mechanism by which coenzyme B12
      (adenosylcobalamin, AdoCbl)-dependent enzymes promote homolytic cleavage of the
      cofactor's Co-C bond to initiate catalysis has continued to elude researchers. In
      this work, we utilized magnetic circular dichroism spectroscopy to explore how
      the electronic structure of the reduced B12 cofactor (i.e., the post-homolysis
      product Co2+ Cbl) is modulated by the enzyme methylmalonyl-CoA mutase. Our data
      reveal a fairly uniform stabilization of the Co 3d orbitals relative to the
      corrin pi/pi*-based molecular orbitals when Co2+ Cbl is bound to the enzyme
      active site, particularly in the presence of substrate. Contrastingly, our
      previous studies (Brooks, A. J.; Vlasie, M.; Banerjee, R.; Brunold, T. C. J. Am.
      Chem. Soc. 2004, 126, 8167-8180.) showed that when AdoCbl is bound to the MMCM
      active site, no enzymatic perturbation of the Co3+ Cbl electronic structure
      occurs, even in the presence of substrate (analogues). Collectively, these
      observations provide direct evidence that enzymatic Co-C bond activation involves
      stabilization of the post-homolysis product, Co2+ Cbl, rather than
      destabilization of the Co3+ Cbl "ground" state.

PMID- 16305241
TI  - Experimental evidence for ultrafast electronic relaxation in molecules, mediated
      by diffuse states.
AB  - The existence of a mediating state for the ultrafast electronic relaxation in
      ethylenic-like molecules has been shown by femtosecond electron imaging
      techniques. This state is of Rydberg character, and its high efficiency is due to
      its ability to link the electron distributions of the initial and final
      electronic states.

PMID- 16305242
TI  - Calcium ion responsive DNA binding in a zinc finger fusion protein.
AB  - Zinc finger fusion proteins, having a Ca-binding site from troponin C, were
      created to develop Ca-responsive regulation of DNA binding. The typical zinc
      finger folding of a novel fusion protein with a single finger, F2-Tn, was
      investigated using UV-vis spectroscopy of the Co-substituted form and CD
      experiments. Detailed structural analyses of F2-Tn/Zn2+ using NMR experiments and
      structural calculations clarify that our fusion protein gives a native zinc
      finger folding with the artificial Ca-binding domain intervening two helices. The
      Ca-responsive DNA-binding affinity of troponin-fused protein with two fingers
      (using F1F2-Tn) was investigated by electrophoretic mobility shift assay (EMSA).
      EMSA analyses of F1F2-Tn were performed under the conditions of various
      concentrations of the Ca ion. F1F2-Tn has a Kd value of 5.8 nM in the absence of
      Ca ion and shows a higher Kd value of 13 nM in the presence of 100 equiv of Ca
      ion. The artificially designed fusion zinc finger protein with a Ca-binding
      domain has Ca-responsive DNA-binding affinity. It is leading to a better
      understanding of the construction of zinc finger-based artificial transcriptional
      factors with a Ca switch.

PMID- 16305243
TI  - Role of heme types in heme-copper oxidases: effects of replacing a heme b with a
      heme o mimic in an engineered heme-copper center in myoglobin.
AB  - To address the role of the secondary hydroxyl group of heme a/o in heme-copper
      oxidases, we incorporated Fe(III)-2,4 (4,2) hydroxyethyl vinyl deuterioporphyrin
      IX, as a heme o mimic, into the engineered heme-copper center in myoglobin (sperm
      whale myoglobin L29H/F43H, called Cu(B)Mb). The only difference between the heme
      b of myoglobin and the heme o mimic is the substitution of one of the vinyl side
      chains of the former with a hydroxyethyl group of the latter. This substitution
      resulted in an approximately 4 nm blue shift in the Soret band and approximately
      20 mV decrease in the heme reduction potential. In a control experiment, the heme
      b in Cu(B)Mb was also replaced with a mesoheme, which resulted in an
      approximately 13 nm blue shift and approximately 30 mV decrease in the heme
      reduction potential. Kinetic studies of the heme o mimic-substituted Cu(B)Mb
      showed significantly different reactivity toward copper-dependent oxygen
      reduction from that of the b-type Cu(B)Mb. In reaction with O2, Cu(B)Mb with a
      native heme b showed heme oxygenase activity by generating verdoheme in the
      presence of Cu(I). This heme degradation reaction was slowed by approximately 19
      fold in the heme o mimic-substituted Cu(B)Mb (from 0.028 s(-1) to 0.0015 s(-1)),
      while the mesoheme-substituted Cu(B)Mb shared a similar heme degradation rate
      with that of Cu(B)Mb (0.023 s(-1)). No correlation was found between the heme
      reduction potential and its O2 reactivity. These results strongly suggest the
      critical role of the hydroxyl group of heme o in modulating heme-copper oxidase
      activity through participation in an extra hydrogen-bonding network.

PMID- 16305244
TI  - Spectroscopic studies of metal binding and metal selectivity in Bacillus subtilis
      BSco, a Homologue of the Yeast Mitochondrial Protein Sco1p.
AB  - Sco1 is a mitochondrial membrane protein involved in the assembly of the CuA site
      of cytochrome c oxidase. The Bacillus subtilis genome contains a homologue of
      yeast Sco1, YpmQ (hereafter termed BSco), deletion of which leads to a phenotype
      lacking in caa3 (CuA-containing) oxidase activity but expressing normal levels of
      aa3 (quinol) oxidase activity. Here, we report the characterization of the metal
      binding site of BSco in its Cu(I)-, Cu(II)-, Zn(II)-, and Ni(II)-bound forms. Apo
      BSco was found to bind Cu(II), Zn(II), and Ni(II) at a 1:1 protein/metal ratio.
      The Cu(I) protein could be prepared by either dithionite reduction of the Cu(II)
      derivative or by reconstitution of the apo protein with Cu(I). X-ray absorption
      (XAS) spectroscopy showed that Cu(I) was coordinated by two cysteines at 2.22 +/-
      0.01 A and by a weakly bound low-Z scatterer at 1.95 +/- 0.03 A. The Cu(II)
      derivative was reddish-orange and exhibited a strong type-2 thiolate to Cu(II)
      transition around 350 nm. Multifrequency electron paramagnetic resonance (EPR),
      electron-nuclear double resonance (ENDOR), and electron spin-echo envelope
      modulation (ESEEM) studies on the Cu(II) derivative provided evidence of one
      strongly coupled histidine residue, at least one strongly coupled cysteine, and
      coupling to an exchangeable proton. XAS spectroscopy indicated two cysteine
      ligands at 2.21 A and two O/N donor ligands at 1.95 A, at least one of which is
      derived from a coordinated histidine. The Zn(II) and Ni(II) derivatives were 4
      coordinate with MS2N(His)X coordination. These results provide evidence that a
      copper chaperone can engage in redox chemistry at the metal center and may
      suggest interesting redox-based mechanisms for metalation of the mixed-valence
      CuA center of cytochrome c oxidase.

PMID- 16305245
TI  - Synthesis and characterization of a highly reducing neutral "extended viologen"
      and the isostructural hydrocarbon 4,4''''-di-n-octyl-p-quaterphenyl.
AB  - The molecule 4,4''''-di-n-octyl-p-quaterphenyl was synthesized in one step by a
      nickel-catalyzed cross-coupling reaction. Powder X-ray diffraction shows that it
      crystallizes in a layered structure with the long axis of the molecule nearly
      perpendicular to the layer plane. Differential scanning calorimetry indicates a
      transition to a liquid-crystalline phase at 81 degrees C. Reaction of 4,4'-bis(4
      pyridyl)biphenyl with 1-bromooctane yields the dication 2(2+) 2Br-, an "extended
      viologen" isostructural with 4,4''''-di-n-octyl-p-quaterphenyl. Reduction of
      2(2+) 2Br- with sodium amalgam in DMF yields 2, the first neutral extended
      viologen to be isolated. The molecule 2 is, to the best of our knowledge, the
      most reducing neutral organic molecule that has been synthesized. Single-crystal
      X-ray diffraction shows that a diradical form, either singlet or triplet, makes
      an important contribution to the electronic structure of 2. The broadened 1H NMR
      spectrum of 2 indicates the presence of a triplet, but it has not been possible
      to observe the triplet by ESR spectroscopy. The electronic structure of 2 appears
      to be closely related to that of a classic molecule, Chichibabin's hydrocarbon.

PMID- 16305246
TI  - Spectroscopic and kinetic studies of Arabidopsis thaliana sulfite oxidase: nature
      of the redox-active orbital and electronic structure contributions to catalysis.
AB  - Plant sulfite oxidase from Arabidopsis thaliana has been characterized both
      spectroscopically and kinetically. The enzyme is unusual in lacking the heme
      domain that is present in the otherwise highly homologous enzyme from vertebrate
      sources. In steady-state assays, the enzyme exhibits a pH maximum of 8.5 and is
      also found to function as a selenite oxidase. Sulfite at the lowest
      experimentally feasible concentrations reduces the enzyme within the dead-time of
      a stopped-flow instrument at 5 degrees C, indicating that the A. thaliana enzyme
      has a limiting rate constant for reduction, k(red), at least 10 times greater
      than that of the chicken enzyme (190 s(-1)). The EPR parameters for the high- and
      low-pH forms of the A. thaliana enzyme have been determined, and the g-values are
      found to resemble those previously reported for the vertebrate enzymes. Finally,
      the A. thaliana enzyme has been probed by resonance Raman spectroscopy. A
      detailed analysis of the vibrational spectrum in the region where Mo=O stretching
      modes are anticipated to occur has been performed with the help of density
      functional theory calculations, evaluated in the context of the Raman data.
      Calculated frequencies obtained for two model systems have been compared to
      experimental resonance Raman spectra of oxidized A. thaliana sulfite oxidase
      catalytically cycled in both H2(16)O and H2(18)O. The vibrational frequency
      shifts observed upon (18)O-labeling of the enzyme are consistent with theoretical
      models in which either the equatorial oxygen or both equatorial and axial atoms
      of the dioxomolybdenum center are labeled. Importantly, the vibrational mode
      description is consistent with the active site possessing geometrically
      inequivalent oxo ligands and a Mo d(xy) redox-active molecular orbital oriented
      in the equatorial plane forming a pi-bonding interaction solely with the
      equatorial oxo, O(eq). Electron occupancy of this Mo=O(eq) pi* redox orbital upon
      interaction with substrates would effectively labilize the Mo=O(eq) bond,
      providing the dominant contribution to lowering the activation energy for oxygen
      atom transfer.

PMID- 16305247
TI  - Carbohydrate rod conjugates: ternary rod-coil molecules forming complex liquid
      crystal structures.
AB  - T-shaped polyphilic triblock molecules, consisting of a rodlike p-terphenyl unit,
      a hydrophilic and flexible laterally attached oligo(oxyethylene) chain terminated
      by an 1-acylamino-1-deoxy-D-sorbitol unit, and two end-attached lipophilic alkyl
      chains, have been synthesized by palladium-catalyzed cross-coupling reactions as
      the key steps. The thermotropic liquid crystalline behavior of these compounds
      was investigated by polarized light microscopy, differential scanning calorimetry
      (DSC), and X-ray scattering. We investigated the mode of self-organization as a
      function of the length and position of the lateral polar chain and the length of
      the terminal alkyl chains. Depending on the size of the polar and lipophilic
      segments, a series of unusual liquid crystalline phases was detected. In three of
      these phases, the space is divided into three distinct periodic subspaces. In
      addition to a hexagonal channeled layer phase (ChL(hex)) consisting of layers
      that are penetrated by polar columns, there are also two honeycomb-like network
      structures formed by square (Col(squ)/p4mm) or pentagonal cylinders
      (Col(squ)/p4gm). The cylinder walls consist of the terphenyl units fused by
      columns of alkyl chains, and the interior contains the polar side chains. In
      addition, a hexagonal columnar phase was observed in which the polar columns are
      organized in a continuum of terphenyls and alkyl chains with an organization of
      the terphenyl cores tangentially around the columns with the long axis
      perpendicular to the columns. For one compound, a reversal of birefringence was
      observed, which is explained by a reorientation of the terphenyl cores. The
      addition of protic solvents induces lamellar phases.

PMID- 16305248
TI  - Chemical basis of DNA sugar-phosphate cleavage by low-energy electrons.
AB  - DNA damage by low-energy electrons (LEE) was examined using a novel system in
      which thin solid films of oligonucleotide tetramers (CGTA and GCAT) were
      irradiated with monoenergetic electrons (10 eV) under ultrahigh vacuum. The
      products of irradiation were examined by HPLC. These analyses permitted the
      quantitation of 16 nonmodified nucleobase, nucleoside, and nucleotide fragments
      of each tetramer resulting from the cleavage of phosphodiester and N-glycosidic
      bonds. The distribution of nonmodified products suggests a mechanism of damage
      involving initial electron attachment to nucleobase moieties, followed by
      electron transfer to the sugar-phosphate backbone, and subsequent dissociation of
      the phosphodiester bond. Moreover, virtually all the nonmodified fragments
      contained a terminal phosphate group at the site of cleavage. These results
      demonstrate that the phosphodiester bond breaks by a distinct pathway in which
      the negative charge localizes on the phosphodiester bond giving rise to
      nonmodified fragments with an intact phosphate group. Conversely, the radical
      must localize on the sugar moiety to give as yet unidentified modifications. In
      summary, the reaction of LEE with simple tetramers involved dissociative electron
      attachment leading to phosphodiester bond cleavage and the formation of
      nonmodified fragments.

PMID- 16305249
TI  - Solvation dynamics in Ni+ (H2O)n clusters probed with infrared spectroscopy.
AB  - Infrared photodissociation spectroscopy is reported for mass-selected Ni+ (H2O)n
      complexes in the O-H stretching region up to cluster sizes of n = 25. These
      clusters fragment by the loss of one or more intact water molecules, and their
      excitation spectra show distinct bands in the region of the symmetric and
      asymmetric stretches of water. The first evidence for hydrogen bonding, indicated
      by a broad band strongly red-shifted from the free OH region, appears at the
      cluster size of n = 4. At larger cluster sizes, additional red-shifted structure
      evolves over a broader wavelength range in the hydrogen-bonding region. In the
      free OH region, the symmetric stretch gradually diminishes in intensity, while
      the asymmetric stretch develops into a closely spaced doublet near 3700 cm(-1).
      The data indicate that essentially all of the water molecules are in a hydrogen
      bonded network by the size of n = 10. However, there is no evidence for the
      formation of clathrate structures seen recently via IR spectroscopy of protonated
      water clusters.

PMID- 16305250
TI  - Time-scale- and temperature-dependent mechanical properties of viscoelastic
      poly(3,4-ethylenedioxythiophene) films.
AB  - The viscoelastic properties of thin films of poly(3,4-ethylenedioxythiophene)
      (PEDOT) have been studied using the method of acoustic impedance. The films were
      deposited on the Au electrodes of 10 MHz AT-cut quartz thickness shear mode
      resonators and exposed to acetonitrile solutions of 0.1 M TEABF4 and LiClO4. For
      p-doped films, admittance spectra as a function of potential (E), temperature
      (T), and time scale (frequency, via harmonics, in the range 10-110 MHz) were
      acquired. Shear modulus components extracted from these responses surprisingly
      showed virtually no variation with E (and thus film solvation) or with T, but the
      variation with frequency was dramatic. This qualitative behavior and the
      numerical values of the shear moduli contrast strongly with recently reported
      data for the related poly(3-hexylthiophene) system, which shares the same
      conducting spine but differs substantially in the substitution pattern.
      Accordingly, the models and interpretation for PEDOT are quite different: film
      dynamics are determined by free-volume effects, and side-chain motion is not a
      significant factor. Qualitatively similar potential and time-scale effects were
      seen for n-doped PEDOT, but the scope of the measurements was limited by film
      stability.

PMID- 16305251
TI  - Refinement of multidomain protein structures by combination of solution small
      angle X-ray scattering and NMR data.
AB  - Determination of the 3D structures of multidomain proteins by solution NMR
      methods presents a number of unique challenges related to their larger molecular
      size and the usual scarcity of constraints at the interdomain interface, often
      resulting in a decrease in structural accuracy. In this respect, experimental
      information from small-angle scattering of X-ray radiation in solution (SAXS)
      presents a suitable complement to the NMR data, as it provides an independent
      constraint on the overall molecular shape. A computational procedure is described
      that allows incorporation of such SAXS data into the mainstream high-resolution
      macromolecular structure refinement. The method is illustrated for a two-domain
      177-amino-acid protein, gammaS crystallin, using an experimental SAXS data set
      fitted at resolutions from approximately 200 A to approximately 30 A. Inclusion
      of these data during structure refinement decreases the backbone coordinate root
      mean-square difference between the derived model and the high-resolution crystal
      structure of a 54% homologous gammaB crystallin from 1.96 +/- 0.07 A to 1.31 +/-
      0.04 A. Combining SAXS data with NMR restraints can be accomplished at a moderate
      computational expense and is expected to become useful for multidomain proteins,
      multimeric assemblies, and tight macromolecular complexes.

PMID- 16305252
TI  - Imido transfer from bis(imido)ruthenium(VI) porphyrins to hydrocarbons: effect of
      imido substituents, C-H bond dissociation energies, and Ru(VI/V) reduction
      potentials.
AB  - [Ru(VI)(TMP)(NSO2R)2] (SO2R = Ms, Ts, Bs, Cs, Ns; R = p-C6H4OMe, p-C6H4Me, C6H5,
      p-C6H4Cl, p-C6H4NO2, respectively) and [Ru(VI)(Por)(NTs)2] (Por = 2,6-Cl2TPP, F20
      TPP) were prepared by the reactions of [Ru(II)(Por)(CO)] with PhI=NSO2R in
      CH2Cl2. These complexes exhibit reversible Ru(VI/V) couple with E(1/2) = -0.41 to
      -0.12 V vs Cp2Fe(+/0) and undergo imido transfer reactions with styrenes,
      norbornene, cis-cyclooctene, indene, ethylbenzenes, cumene, 9,10
      dihydroanthracene, xanthene, cyclohexene, toluene, and tetrahydrofuran to afford
      aziridines or amides in up to 85% yields. The second-order rate constants (k2) of
      the aziridination/amidation reactions at 298 K were determined to be (2.6 +/-
      0.1) x 10(-5) to 14.4 +/- 0.6 dm3 mol(-1) s(-1), which generally increase with
      increasing Ru(VI/V) reduction potential of the imido complexes and decreasing C-H
      bond dissociation energy (BDE) of the hydrocarbons. A linear correlation was
      observed between log k' (k' is the k2 value divided by the number of reactive
      hydrogens) and BDE and between log k2 and E(1/2)(Ru(VI/V)); the linearity in the
      former case supports a H-atom abstraction mechanism. The amidation by
      [Ru(VI)(TMP)(NNs)2] reverses the thermodynamic reactivity order cumene >
      ethylbenzene/toluene, with k'(tertiary C-H)/k'(secondary C-H) = 0.2 and
      k'(tertiary C-H)/k'(primary C-H) = 0.8.

PMID- 16305253
TI  - A photocycle for hydrogen production from two-electron mixed-valence complexes.
AB  - Dihydrides of the formula Rh2(II,II)(tfepma)3H2Cl2 (tfepma =
      (bis[bis(trifluoroethoxy)phosphino]methylamine, MeN(P[OCH2CF3]2)2), have been
      prepared by the addition of H2 to the two-electron mixed-valence complex,
      Rh2(0,II)(tfepma)3Cl2 (1). Three isomeric forms with hydrides in syn (2), anti
      (3), and cis (4) conformations have been characterized by X-ray diffraction.
      Photolysis of 2 results in prompt formation of a short-lived blue photoproduct
      (lambda(max) = 600 nm) and a stoichiometric quantity of H2, as determined by
      Toepler pump and isotopic labeling experiments. The blue photoproduct was
      identified as a Rh2(I,I) complex resulting from the reductive elimination of H2,
      as determined from the examination of bimetallic cores coordinated by tfepm
      (tfepm = (bis[bis(trifluoroethoxy)phosphino]methane, CH2(P[OCH2CF3]2)2), for
      which complexes of the formula M2(I,I)(tfepm)3Cl2 (5, M = Rh and 6, M = Ir) have
      been isolated. The d8...d8 dimer of 5 converts to Rh2(0,II)(tfepm)3Cl2CN(t)Bu (8)
      upon the addition of 1 equiv of tert-butylisonitrile, a result of halogen
      migration and disproportionation of the valence symmetric core of 5, which is
      structurally compared to its two-electron mixed-valence analogue,
      Rh2(0,II)(dfpma)3Cl2CN(t)Bu (9) (dfpma = bis(difluorophosphino)methylamine,
      MeN(PF2)2). The halogen migration is captured in Ir2(I,I)(tfepm)3(mu-Cl)Cl (7),
      which is distinguished by the presence of a chloride that bridges the diiridium
      centers. Taken together, complexes 1-9 permit the construction of a complete
      photocycle for the photogeneration of H2 by dirhodium dfpma complexes in
      homogeneous solutions of hydrohalic acids.

PMID- 16305255
TI  - Secondary structure sensitivity of hydrogen bond lifetime dynamics in the protein
      hydration layer.
AB  - The heterogeneous nature of a protein surface plays an essential role in its
      biological activity and molecular recognition, and this role is mediated at least
      partly through the surrounding water molecules. We have performed atomistic
      molecular dynamics simulations of an aqueous solution of HP-36 to investigate the
      correlation between the dynamics of the hydration layer water molecules and the
      lifetimes of protein-water hydrogen bonds. The nonexponential hydrogen bond
      lifetime correlation functions have been analyzed by using the formalism of Luzar
      and Chandler, which allowed identification of the quasi-bound states in the
      surface and quantification of the dynamic equilibrium between quasi-bound and
      free water molecules in terms of time-dependent rate of interconversion. It is
      noticed that, irrespective of the structural heterogeneity of different segments
      of the protein, namely the three alpha-helices, the positively charged amino acid
      residues form longer-lived hydrogen bonds with water. The overall relaxation
      behavior of protein-water hydrogen bonds is found to differ significantly among
      the three helices of the protein. Study of water number density fluctuation
      reveals that the hydration layer of helix-3 is much less rigid, which can be
      correlated with faster structural relaxation of the hydrogen bonds between its
      residues and water. This also agrees excellently with faster translational and
      rotational motions of water near helix-3, and hence the lower rigidity of its
      hydration layer. The lower rigidity of the helix-3 hydration layer also
      correlates well with the biological activity of the protein, as several of the
      active-site residues of HP-36 are located in helix-3.

PMID- 16305254
TI  - Boronate-based fluorescent probes for imaging cellular hydrogen peroxide.
AB  - The syntheses, properties, and biological applications of the Peroxysensor
      family, a new class of fluorescent probes for hydrogen peroxide, are presented.
      These reagents utilize a boronate deprotection mechanism to provide high
      selectivity and optical dynamic range for detecting H2O2 in aqueous solution over
      similar reactive oxygen species (ROS) including superoxide, nitric oxide, tert
      butyl hydroperoxide, hypochlorite, singlet oxygen, ozone, and hydroxyl radical.
      Peroxyresorufin-1 (PR1), Peroxyfluor-1 (PF1), and Peroxyxanthone-1 (PX1) are
      first-generation probes that respond to H2O2 by an increase in red, green, and
      blue fluorescence, respectively. The boronate dyes are cell-permeable and can
      detect micromolar changes in H2O2 concentrations in living cells, including
      hippocampal neurons, using confocal microscopy and two-photon microscopy. The
      unique combination of ROS selectivity, membrane permeability, and a range of
      available excitation/emission colors establishes the potential value of PR1, PF1,
      PX1, and related probes for interrogating the physiology and pathology of
      cellular H2O2.

PMID- 16305256
TI  - Polypeptide helices in hybrid peptide sequences.
AB  - A new class of polypeptide helices in hybrid sequences containing alpha-, beta-,
      and gamma-residues is described. The molecular conformations in crystals
      determined for the synthetic peptides Boc-Leu-Phe-Val-Aib-betaPhe-Leu-Phe-Val-OMe
      1 (betaPhe: (S)-beta3-homophenylalanine) and Boc-Aib-Gpn-Aib-Gpn-OMe 2(Gpn: 1
      (aminomethyl)cyclohexaneacetic acid) reveal expanded helical turns in the hybrid
      sequences (alpha alphabeta)n and (alphagamma)n. In 1, a repetitive helical
      structure composed of C14 hydrogen-bonded units is observed, whereas 2 provides
      an example of a repetitive C12 hydrogen-bonded structure. Using experimentally
      determined backbone torsion angles for the hydrogen-bonded units formed by hybrid
      sequences, we have generated energetically favorable hybrid helices.
      Conformational parameters are provided for C11, C12, C13, C14, and C15 helices in
      hybrid sequences.

PMID- 16305257
TI  - Hydrogen storage in magnesium clusters: quantum chemical study.
AB  - Magnesium hydride is cheap and contains 7.7 wt % hydrogen, making it one of the
      most attractive hydrogen storage materials. However, thermodynamics dictate that
      hydrogen desorption from bulk magnesium hydride only takes place at or above 300
      degrees C, which is a major impediment for practical application. A few results
      in the literature, related to disordered materials and very thin layers, indicate
      that lower desorption temperatures are possible. We systematically investigated
      the effect of crystal grain size on the thermodynamic stability of magnesium and
      magnesium hydride, using ab initio Hartree-Fock and density functional theory
      calculations. Also, the stepwise desorption of hydrogen was followed in detail.
      As expected, both magnesium and magnesium hydride become less stable with
      decreasing cluster size, notably for clusters smaller than 20 magnesium atoms.
      However, magnesium hydride destabilizes more strongly than magnesium. As a
      result, the hydrogen desorption energy decreases significantly when the crystal
      grain size becomes smaller than approximately 1.3 nm. For instance, an MgH2
      crystallite size of 0.9 nm corresponds to a desorption temperature of only 200
      degrees C. This predicted decrease of the hydrogen desorption temperature is an
      important step toward the application of Mg as a hydrogen storage material.

PMID- 16305258
TI  - Stable, specific, and reversible base pairing via Schiff base.
AB  - We here present a novel covalently linked base pair via Schiff base formation
      between 5-formyluracil (fU) and 5-aminocytosine (AmC). Formation of the Schiff
      base linkage proceeds reversibly and does not require any additives. The cross
      linked DNA is very stable under denaturing conditions, whereas it completely
      dissociates upon heating at 90 degrees C. The pairing ability of AmC and fU is
      very specific and is applicable to the detection of fU, which is the major
      oxidative lesion of T in DNA. We propose the Schiff base linkage as a new
      artificial base pairing scheme to create functional DNAs.

PMID- 16305259
TI  - Sequence-specific fluorescence detection of DNA by polyamide-thiazole orange
      conjugates.
AB  - Fluorescent methods to detect specific double-stranded DNA sequences without the
      need for denaturation may be useful in the field of genetics. Three hairpin
      pyrrole-imidazole polyamides 2-4 that target their respective sequences 5'-WGGGWW
      3', 5'-WGGCCW-3', and 5'-WGWWCW-3' (W = A or T) were conjugated to thiazole
      orange dye at the C-termini to examine their fluorescence properties in the
      presence and absence of match duplex DNA. The conjugates fluoresce weakly in the
      absence of DNA but showed significant enhancement (>1000-fold) upon the addition
      of 1 equiv of match DNA and only slight enhancement with the addition of mismatch
      DNA. The polyamide-dye conjugates bound specific DNA sequences with high affinity
      (Ka > 10(8) M(-1)) and unwound the DNA duplex through intercalation (unwinding
      angle, phi, approximately 8 degrees). This new class of polyamides provides a
      method to specifically detect DNA sequences without denaturation.

PMID- 16305260
TI  - Laminated morphology of nontwisting beta-sheet fibrils constructed via peptide
      self-assembly.
AB  - A synthetic peptide has been de novo designed that self-assembles into beta-sheet
      fibrils exhibiting a nontwisted, stacked morphology. The stacked morphology is
      constituted by 2.5 nm wide filaments that laterally associate to form flat fibril
      laminates exceeding 50 nm in width and micrometers in length. The height of each
      fibril is limited to the length of exactly one peptide monomer in an extended
      beta-strand conformation, approximately 7 nm. Once assembled, these highly
      ordered, 2-D structures are stable over a wide range of pH and temperature and
      exhibit characteristics similar to those of amyloid fibrils. Furthermore, the
      rate of assembly and degree of fibril lamination can be controlled with kinetic
      parameters of pH and temperature. Finally, the presence of a diproline peptide
      between two beta-sheet-forming strands in the peptide sequence is demonstrated to
      be an important factor in promoting the nontwisting, laminated fibril morphology.

PMID- 16305261
TI  - Dynamic effects in MAS and MQMAS NMR spectra of half-integer quadrupolar nuclei:
      calculations and an application to the double perovskite cryolite.
AB  - Dynamic processes such as chemical exchange or rotations between inequivalent
      orientations can affect the magic-angle spinning (MAS) and the multiple-quantum
      (MQ) MAS NMR spectra of half-integer quadrupolar nuclei. The present paper
      discusses such dynamic multisite MAS and MQMAS effects and applies them to study
      the dynamic processes that occur in the double perovskite cryolite, Na3AlF6.
      Dynamic line shape simulations invoking a second-order broadening of the central
      transition and relying on the semiclassical Bloch-McConnell formalism for
      chemical exchange were performed for a variety of exchange models possessing
      different symmetries. Fitting experimental variable-temperature cryolite 23Na NMR
      data with this formalism revealed that the two inequivalent sodium sites in this
      mineral undergo an exchange characterized by a broad distribution of rates. To
      further assess this dynamic process a variety of 27Al and 19F MAS NMR studies
      were also undertaken; quantitative 27Al-19F dipolar coupling measurements then
      revealed a dynamic motion of the AlF6 octahedra that were qualitatively
      consistent with predictions stemming from molecular dynamic simulations on this
      double perovskite.

PMID- 16305262
TI  - Pulsed EPR investigations of systems modeling molybdenum enzymes: hyperfine and
      quadrupole parameters of oxo-17O in [Mo 17O(SPh)4]-.
AB  - Ka band ESEEM spectroscopy was used to determine the hyperfine (hfi) and nuclear
      quadrupole (nqi) interaction parameters for the oxo-17O ligand in [Mo 17O(SPh)4]
      , a spectroscopic model of the oxo-Mo(V) centers of enzymes. The isotropic hfi
      constant of 6.5 MHz found for the oxo-17O is much smaller than the values of
      approximately 20-40 MHz typical for the 17O nucleus of an equatorial OH(2) ligand
      in molybdenum enzymes. The 17O nqi parameter (e2qQ/h = 1.45 MHz, eta
      approximately = 0) is the first to be obtained for an oxo group in a metal
      complex. The parameters of the oxo-17O ligand, as well as other magnetic
      resonance parameters of [Mo 17O(SPh)4]- predicted by quasi-relativistic DFT
      calculations, were in good agreement with those obtained in experiment. From the
      electronic structure of the complex revealed by DFT, it follows that the SOMO is
      almost entirely molybdenum d(xy) and sulfur p, while the spin density on the oxo
      17O is negative, determined by spin polarization mechanisms. The results of this
      work will enable direct experimental identification of the oxo ligand in a
      variety of chemical and biological systems.

PMID- 16305263
TI  - 205Tl NMR methods for the characterization of monovalent cation binding to
      nucleic acids.
AB  - Monovalent cations play an important role in many biological functions. The
      guanine rich sequence, d(G4T4G4), requires monovalent cations for formation of
      the G-quadruplex, d(G4T4G4)2. This requirement can be satisfied by thallium
      (Tl+), a potassium (K+) surrogate. To verify that the structure of d(G4T4G4)2 in
      the presence of Tl+ is similar to the K+-form of the G-quadruplex, the solution
      structure of the Tl+-form of d(G4T4G4)2 was determined. The 10 lowest energy
      structures have an all atom RMSD of 0.76 +/- 0.16 A. Comparison of this structure
      to the identical G-quadruplex formed in the presence of K+ validates the
      isomorphous nature of Tl+ and K+. Using a 1H-205Tl spin-echo difference
      experiment we show that, in the Tl+-form of d(G4T4G4)2, small scalar couplings
      (<1 Hz) exist between 205Tl and protons in the G-quadruplex. These data comprise
      the first 1H-205Tl scalar couplings observed in a biological system and have the
      potential to provide important constraints for structure determination. These
      experiments can be applied to any system in which the substituted Tl+ cations are
      in slow exchange with the bulk ions in solution.

PMID- 16305264
TI  - Toward a molecular scale interpretation of excitation energy transfer in solvated
      bichromophoric systems.
AB  - This paper presents a quantum-mechanical study of the intramolecular excitation
      energy transfer (EET) coupling in naphthalene-bridge-naphthalene systems in gas
      phase and in solution. ZINDO and TDDFT response schemes are compared using both
      an exact and an approximate solution. The approximate solution based on a
      perturbative approach uses the single chromophore properties to reconstruct the
      real system coupling thus neglecting possible through-bond effects which
      conversely are accounted for in the exact solution. The comparison of the results
      of the two approaches with the experiments allows a detailed analysis of the
      relative importance of through-bond and through-space effects as well as a more
      complete understanding of the modifications in the EET coupling with the size of
      the system, the chromophore-chromophore distance, and solvation.

PMID- 16305267
TI  - Physiologic evidence for high-frequency chest wall oscillation and positive
      expiratory pressure breathing in hospitalized subjects with cystic fibrosis.
AB  - BACKGROUND AND PURPOSE: This investigation identified ventilation distribution,
      gas mixing, lung function, and arterial blood oxyhemoglobin saturation (SpO2)
      physiologic responses to 2 independent airway clearance treatments, high
      frequency chest wall oscillation (HFCWO) and low positive expiratory pressure
      (PEP) breathing, for subjects who had cystic fibrosis (CF) and who were
      hospitalized during acute and subacute phases of a pulmonary exacerbation.
      SUBJECTS: Fifteen subjects with moderate to severe CF were included in this
      study. METHODS: Subjects performed single-breath inert gas tests and spirometry
      before and immediately after HFCWO and PEP breathing at admission and discharge.
      Arterial blood oxyhemoglobin saturation was monitored throughout each treatment.
      RESULTS: At admission and discharge, PEP breathing increased SpO2 during
      treatment, whereas HFCWO decreased SpO2 during treatment. Ventilation
      distribution, gas mixing, and lung function improved after HFCWO or PEP
      breathing. DISCUSSION AND CONCLUSION: High-frequency chest wall oscillation and
      PEP breathing are similarly efficacious in improving ventilation distribution,
      gas mixing, and pulmonary function in hospitalized people with CF. Because SpO2
      decreases during HFCWO, people who have moderate to severe CF and who use HFCWO
      should have SpO2 monitored during an acute exacerbation.

PMID- 16305268
TI  - Management of symphysis pubis dysfunction during pregnancy using exercise and
      pelvic support belts.
AB  - BACKGROUND AND PURPOSE: Symphysis pubis pain is a significant problem for some
      pregnant women. The purpose of this study was to investigate the effects of
      exercise, advice, and pelvic support belts on the management of symphysis pubis
      dysfunction during pregnancy. SUBJECTS: Ninety pregnant women with symphysis
      pubis dysfunction were randomly assigned to 3 treatment groups. METHODS: A
      randomized masked prospective experimental clinical trial was conducted. Specific
      muscle strengthening exercises and advice concerning appropriate methods for
      performing activities of daily living were given to the 3 groups, and 2 of the
      groups were given either a rigid pelvic support belt or a nonrigid pelvic support
      belt. The dependent variables, which were measured before and after the
      intervention, were a Roland-Morris Questionnaire score, a Patient-Specific
      Functional Scale score, and a pain score (101-point numerical rating score).
      RESULTS: After the intervention, there was a significant reduction in the Roland
      Morris Questionnaire score, the Patient-Specific Functional Scale score, and the
      average and worst pain scores in all groups. With the exception of average pain,
      there were no significant differences between groups for the other measures.
      DISCUSSION AND CONCLUSION: The findings indicate that the use of either a rigid
      or a nonrigid pelvic support belt did not add to the effects provided by exercise
      and advice.

PMID- 16305269
TI  - Physical therapy treatment effectiveness for osteoarthritis of the knee: a
      randomized comparison of supervised clinical exercise and manual therapy
      procedures versus a home exercise program.
AB  - BACKGROUND AND PURPOSE: Manual therapy and exercise have not previously been
      compared with a home exercise program for patients with osteoarthritis (OA) of
      the knee. The purpose of this study was to compare outcomes between a home-based
      physical therapy program and a clinically based physical therapy program.
      SUBJECTS: One hundred thirty-four subjects with OA of the knee were randomly
      assigned to a clinic treatment group (n=66; 61% female, 39% male; mean age [+/
      SD]=64+/-10 years) or a home exercise group (n=68, 71% female, 29% male; mean age
      [+/-SD]=62+/-9 years). METHODS: Subjects in the clinic treatment group received
      supervised exercise, individualized manual therapy, and a home exercise program
      over a 4-week period. Subjects in the home exercise group received the same home
      exercise program initially, reinforced at a clinic visit 2 weeks later. Measured
      outcomes were the distance walked in 6 minutes and the Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: Both groups showed
      clinically and statistically significant improvements in 6-minute walk distances
      and WOMAC scores at 4 weeks; improvements were still evident in both groups at 8
      weeks. By 4 weeks, WOMAC scores had improved by 52% in the clinic treatment group
      and by 26% in the home exercise group. Average 6-minute walk distances had
      improved about 10% in both groups. At 1 year, both groups were substantially and
      about equally improved over baseline measurements. Subjects in the clinic
      treatment group were less likely to be taking medications for their arthritis and
      were more satisfied with the overall outcome of their rehabilitative treatment
      compared with subjects in the home exercise group. DISCUSSION AND CONCLUSION:
      Although both groups improved by 1 month, subjects in the clinic treatment group
      achieved about twice as much improvement in WOMAC scores than subjects who
      performed similar unsupervised exercises at home. Equivalent maintenance of
      improvements at 1 year was presumably due to both groups continuing the identical
      home exercise program. The results indicate that a home exercise program for
      patients with OA of the knee provides important benefit. Adding a small number of
      additional clinical visits for the application of manual therapy and supervised
      exercise adds greater symptomatic relief.

PMID- 16305270
TI  - Contribution of psychosocial and mechanical variables to physical performance
      measures in knee osteoarthritis.
AB  - BACKGROUND AND PURPOSE: This cross-sectional study evaluated the relative
      contributions of psychosocial and mechanical variables to physical performance
      measures in people with knee osteoarthritis (OA). SUBJECTS: Fifty-four subjects
      (age, in years: mean=68.3, SD=8.7, range=50-87) with radiographically confirmed
      knee OA were included in this study. METHODS: Physical performance measures
      included the Six-Minute Walk Test (SMW), the Timed "Up & Go" Test (TUG), and a
      stair-climbing task (STR). Responses to psychosocial questionnaires that reflect
      depression, anxiety, and self-efficacy (a person's confidence in his or her
      ability to complete a task) were collected. Mechanical variables measured
      included body mass index and knee strength (force-generating capacity of muscle).
      Stepwise linear regressions were performed with the SMW, TUG, and STR as separate
      dependent variables. RESULTS: Functional self-efficacy explained the greatest
      amount of variance in all performance measures, contributing 45% or more. Knee
      strength and body weight also explained some variance in performance measures.
      Anxiety and depression did not explain any variance in performance. DISCUSSION
      AND CONCLUSION: Physical therapists evaluating the significance of the SMW, TUG,
      and STR scores in subjects with knee OA should note that a large part of each
      score reflects self-efficacy, or confidence, for physical tasks, with some
      contributions from knee strength and body weight.

PMID- 16305271
TI  - Effect of bracing and other conservative interventions in the treatment of
      idiopathic scoliosis in adolescents: a systematic review of clinical trials.
AB  - BACKGROUND AND PURPOSE: Many conservative treatments are available for
      adolescents with idiopathic scoliosis, but the evidence for their accepted use is
      still unclear. The purpose of this study was to evaluate the effectiveness of
      braces and other conservative treatments of idiopathic scoliosis in adolescents
      by systematically reviewing the literature. METHODS: The literature was searched
      in the PubMed, CINAHL, Cochrane, and PEDro databases. Studies were selected if
      the design was a randomized clinical trial or a controlled clinical trial, if all
      patients had an idiopathic scoliosis, if all patients were less than 18 years of
      age during the intervention, and if the type of intervention was a conservative
      one. Two reviewers independently assessed the methodological quality using the
      Delphi list and performed data extraction. Analysis was based on the levels of
      evidence. RESULTS: Thirteen studies met the final inclusion criteria, showing a
      wide range of interventions such as bracing, electrical surface stimulation, and
      exercises. DISCUSSION AND CONCLUSION: The authors conclude that the effectiveness
      of bracing and exercises is not yet established, but might be promising. They
      found no evidence of the effectiveness of electrical stimulation.

PMID- 16305272
TI  - Factors associated with the level of movement-related everyday activity and
      quality of life in people with chronic heart failure.
AB  - BACKGROUND AND PURPOSE: Cardiac rehabilitation has been shown to be effective in
      people with chronic heart failure (CHF), particularly in terms of exercise
      capacity. However, no effects have been found on the level of movement-related
      everyday activity. Therefore, rehabilitation programs also should focus on
      enhancing the level of movement-related everyday activity. The aim of this study
      was to explore factors associated with the level of movement-related everyday
      activity and with quality of life in people with CHF. SUBJECTS AND METHODS:
      Measurements of movement-related everyday activity (using an accelerometry-based
      Activity Monitor), quality of life, and associated factors were performed in 36
      people with stable CHF (New York Heart Association classes II and III). RESULTS:
      Knee flexion and extension torque, and particularly extension torque, were
      significantly associated with movement-related everyday activity (r = .43-.49, P
      < .05), whereas nonphysiological factors such as feelings of being disabled were
      associated with quality of life (r = .37-.77, P < or = .01, P < .05). No
      relationship was found between movement-related everyday activity and quality of
      life (r = .20-.22, P > .05). DISCUSSION AND CONCLUSION: The results indicate that
      knee torque is associated with the level of movement-related everyday activity in
      people with CHF and that quality of life is mediated by nonphysiological factors.

PMID- 16305273
TI  - Reliability of a measurement of neck flexor muscle endurance.
AB  - BACKGROUND AND PURPOSE: Neck flexor muscle endurance has been negatively
      correlated with cervical pain and dysfunction. The purposes of this study were to
      determine rater reliability in subjects both with and without neck pain and to
      determine whether there was a difference in neck flexor muscle endurance between
      the 2 groups. SUBJECTS: Forty-one subjects with and without neck pain were
      enrolled in this repeated-measures reliability study. METHODS: Two raters used an
      isometric neck retraction test to assess neck flexor muscle endurance for all
      subjects during an initial session, and subjects without neck pain returned for
      testing 1 week later. RESULTS: For the group without neck pain, intrarater
      reliability was good to excellent (intraclass correlation coefficient
      [ICC(3,1)]=.82-.91), and interrater reliability was moderate to good
      (ICC[2,1]=.67-.78). The associated standard error of measurement (SEM) ranged
      from 8.0 to 11.0 seconds and from 12.6 to 15.3 seconds, respectively. For the
      group with neck pain, interrater reliability was moderate (ICC[2,1]=.67,
      SEM=11.5). Neck flexor muscle endurance test results for the group without neck
      pain (mean=38.95 seconds, SD=26.4) and the group with neck pain (mean=24.1
      seconds, SD=12.8) were significantly different. DISCUSSION AND CONCLUSION:
      Reliability coefficients differed between the 2 groups and ranged from moderate
      to excellent and improved after the first test session. The interrater
      reliability of data obtained with the neck flexor muscle endurance test in people
      with neck pain must be improved in order for clinicians to distinguish a
      clinically meaningful change from measurement error. Neck flexor muscle endurance
      was both statistically and clinically greater for subjects without neck pain than
      for those with neck pain.

PMID- 16305274
TI  - Locomotor training progression and outcomes after incomplete spinal cord injury.
AB  - BACKGROUND AND PURPOSE: The use of locomotor training with a body-weight-support
      system and treadmill (BWST) and manual assistance has increased in
      rehabilitation. The purpose of this case report is to describe the process for
      retraining walking in a person with an incomplete spinal cord injury (SCI) using
      the BWST and transferring skills from the BWST to overground assessment and
      community ambulation. CASE DESCRIPTION: Following discharge from rehabilitation,
      a man with an incomplete SCI at C5-6 and an American Spinal Injury Association
      (ASIA) Impairment Scale classification of D participated in 45 sessions of
      locomotor training. OUTCOMES: Walking speed and independence improved from 0.19
      m/s as a home ambulator using a rolling walker and a right ankle-foot orthosis to
      1.01 m/s as a full-time ambulator using a cane only for community mobility.
      Walking activity (mean+/-SD) per 24 hours increased from 1,054+/-543 steps to
      3,924+/-1,629 steps. DISCUSSION: In a person with an incomplete SCI, walking
      ability improved after locomotor training that used a decision-making algorithm
      and progression across training environments.

PMID- 16305276
TI  - Complex system approaches: could they enhance the relevance of clinical research?

PMID- 16305277
TI  - Tradition and technology: teaching rural medicine using an internet discussion
      board.
AB  - INTRODUCTION: The aim of the Rural Medicine Rotation (RMR) at the University of
      Queensland is to give all third year medical students exposure to, and an
      understanding of, clinical practice in Australian rural or remote locations.
      Because the primary role of the Rural Clinical School is to improve medical
      recruitment and retention in rural areas, the provision of positive student
      learning experiences and subsequent ability to make adequately informed rural
      career choices is of fundamental importance. A difficulty in achieving this is
      the relatively short period of student clinical placements, in only one or two
      rural or remote locations. A web-based Clinical Discussion Board (CDB) has been
      introduced to address this problem by allowing students at all clinical sites to
      discuss their rural experiences and clinical issues with each other. The
      rationale behind the CDB is to encourage an enhanced understanding of the breadth
      and depth of rural medicine through peer-based learning. METHODS: All third year
      students undertaking the RMR are required to submit a minimum of two original
      contributions, on any clinically related topic, and two replies to other
      submissions on the CDB. At the end of their 8 week rotation, the students
      evaluate the CDB by answering a short survey that focuses on the ease of use and
      access and the educational value of the CDB. A question regarding the influence
      of the RMR on their interest in pursuing a rural medicine career is also asked.
      The CDB transcripts are further analysed for type of article posted, category of
      medicine that was discussed and the specific topic under discussion. RESULTS:
      This article reports on the results from the first two RMR of 2005. A total of 83
      third year medical students undergoing an 8 week rural rotation posted a total of
      819 responses on the CDB. This resulted in 217 individual articles or topics
      discussed within 12 broad medical categories. The student ratings of the ease of
      use and access of the CDB were high, as were their ratings of its educational
      value and its potential to increase knowledge of rural medicine. Likewise, the
      majority of students felt the RMR increased their interest in rural medicine.
      CONCLUSIONS: The CDB offers a unique way to understand the concerns and interests
      of third year medical students immersed in their RMR. It highlights the issues
      they need to discuss with their peers, and offers the potential to guide future
      curriculum changes in response to identified needs. A major advantage of the CDB
      is its ability to enable all students to access a wide variety of rural practice
      experiences by sharing ideas and strategies they encounter. Likewise, the CBD
      encourages the development of deep reflective patterns of learning through a peer
      based process. Equally important is the potential for building professional
      networks, interpersonal relationships, teamwork, collaboration and collegial
      support systems. These networks and relationships are essential for rural
      medicine to help alleviate the possible isolation recognised in rural life.

PMID- 16305278
TI  - Scientific basis for tissue-directed antimicrobial therapy. Introduction.

PMID- 16305275
TI  - The muscular dystrophies: from genes to therapies.
AB  - The genetic basis of many muscular disorders, including many of the more common
      muscular dystrophies, is now known. Clinically, the recent genetic advances have
      improved diagnostic capabilities, but they have not yet provided clues about
      treatment or management. Thanks to better management strategies and therapeutic
      interventions, however, many patients with a muscular dystrophy are more active
      and are living longer. Physical therapists, therefore, are more likely to see a
      patient with a muscular dystrophy, so understanding these muscle disorders and
      their management is essential. Physical therapy offers the most promise in caring
      for the majority of patients with these conditions, because it is unlikely that
      advances in gene therapy will significantly alter their clinical treatment in the
      near future. This perspective covers some of the basic molecular biological
      advances together with the clinical manifestations of the muscular dystrophies
      and the latest approaches to their management.

PMID- 16305279
TI  - Predictive value of double tympanocentesis in acute otitis media.
AB  - Advances in the understanding of acute otitis media (AOM), lessons learned from
      antibacterial trials, and the emergence of pathogens with decreased
      susceptibility to commonly used antibiotics explain the need to redefine the role
      of tympanocentesis. The diagnostic value of tympanocentesis at baseline to
      establish the bacterial cause of AOM is well accepted. However, relevant ethical
      and scientific arguments conclude that repeat (or double) tympanocentesis cannot
      be recommended as routine procedure, either for the individual patient or for
      each treatment trial. Relevant aspects on trial design for AOM, with special
      emphasis on the value of double tympanocentesis, are reviewed.

PMID- 16305280
TI  - Microbiologic surrogate end points in clinical trials of infectious diseases:
      example of acute otitis media trials.
AB  - Clinical outcomes that measure how patients feel, function, or survive are the
      most important and relevant outcomes of therapy in clinical trials and in
      clinical practice. Surrogate end points, which do not directly measure clinical
      benefit to the patient, may function as substitutes for clinical end points in
      clinical trials. Such surrogates are attractive as they may allow measurement of
      outcomes earlier in time or with a smaller sample size than with clinical
      outcomes. Microbiologic biomarkers, such as culture results at a specific time
      after start of therapy, or pharmacodynamic analyses of the effect of drugs on
      organisms often are proposed as surrogate end points in clinical trials of
      therapies for infectious diseases. However, evaluation of biomarkers as surrogate
      end points poses distinct challenges, and only a few biomarkers have been useful
      replacements for clinical end points. Evaluation of biomarkers as potential
      surrogate end points first requires an understanding of the differences among
      measurements of the cause of a disease, risk factors for outcome, and
      measurements of treatment effects. We will discuss the definitions of clinical
      and surrogate end points and the reasons why surrogate end points may not predict
      the true clinical benefit of therapies. We will use the example of the biomarker
      of microbiologic outcomes from tympanocenteses performed during therapy as the
      sole measure of clinical effectiveness in clinical trials of acute otitis media
      to illustrate the challenges in evaluating biomarkers as surrogate end points.

PMID- 16305281
TI  - Comparison of amoxicillin with alternative agents for the treatment of acute
      otitis media in children.
AB  - Expert panels have recommended high-dose amoxicillin (80-90 mg/kg/day) as the
      therapy of choice for uncomplicated acute otitis media in children. This
      recommendation is based primarily on pharmacokinetic data predicting
      bacteriologic cure of most middle ear infections by using amoxicillin at the
      recommended dosage. However, comparisons of aminopenicillin-containing regimens
      with alternative treatments, particularly azithromycin, have not consistently
      demonstrated superiority of the former, even in recent trials with stringent
      designs. Moreover, amoxicillin exposure may perturb nasopharyngeal colonization
      more profoundly than do alternative agents. These perturbations may theoretically
      promote the dissemination of beta-lactam-resistant pneumococci in the community
      more than other drugs approved for use in otitis media. Such findings suggest
      that several factors should be considered when choosing an agent to treat otitis
      media and that reexamination of high-dose amoxicillin as the superior first-line
      agent for this condition might be warranted.

PMID- 16305282
TI  - Uptake, transport, delivery, and intracellular activity of antimicrobial agents.
AB  - Antibiotic interactions with cells, including polymorphonuclear neutrophils, may
      influence therapeutic outcomes. Selected microbes (e.g., Legionella pneumophila)
      may survive ingestion by polymorphonuclear neutrophils and are thus protected
      from the action of antimicrobial agents that remain extracellular. Antibiotics
      that penetrate the cell can kill these microbes. Certain antibiotics are
      concentrated inside phagocytes, and when the phagocyte migrates toward the site
      of infection, the antibiotic-loaded cell carries the active agent to the
      infecting microbes. Active antibiotic may be released when the short-lived
      phagocyte dies. Even microbes considered to be extracellular pathogens, such as
      pneumococci, may survive high concentrations of antibiotic by entering cells.
      Antibiotics that penetrate and are active in cells may aid in enhancing
      therapeutic outcomes and in eliminating the carrier state for some pathogens.

PMID- 16305283
TI  - Murine models of pneumococcal pneumonia and their applicability to the study of
      tissue-directed antimicrobials.
AB  - Animal models have long played a crucial role in the preclinical and
      postmarketing evaluation of antimicrobial drug efficacy. With the alarming rise
      of antibiotic resistance in Streptococcus pneumoniae, such models have received
      increased attention as tools for deriving pharmacodynamic data and for
      determining the clinical significance of drug resistance. This information helps
      us to make therapeutic decisions to optimize efficacy and restrict the further
      promotion of drug resistance. Until now, however, insufficient attention has been
      paid to the special issues that arise in the evaluation of antimicrobials that
      are concentrated in tissue relative to serum or plasma. This article reviews the
      utility of animal models in the evaluation of these tissue-directed antibiotics,
      citing recent attempts to use murine models of pneumococcal pneumonia to
      determine the importance of macrolide resistance. A promising new, low-dose
      aerosol model of pneumonia is briefly presented, as is a discussion of the
      limitations of existing models.

PMID- 16305284
TI  - Microdialysis studies of the distribution of antibiotics into chinchilla middle
      ear fluid.
AB  - For conditions such as acute otitis media, in which antibiotic penetration into
      middle ear fluid (MEF) may be slow or limited, antibiotic plasma levels may not
      reflect the concentrations at the site of infection that are relevant to clinical
      outcome. In such cases, a model is needed that will enable prediction of the time
      course of unbound, pharmacologically active antibiotic levels in MEF. We describe
      the use of microdialysis as a sampling tool for measurement of unbound antibiotic
      concentrations in the MEF of the awake, freely moving chinchilla. Results of
      studies of MEF penetration of the beta-lactam antibiotic, cefdinir, with use of
      this technique are also described. Preliminary results of studies of the
      penetration of antibiotics into MEF of the chinchilla appear consistent with
      clinical findings and suggest that the chinchilla microdialysis model may prove
      to be a useful tool for predicting antibiotic efficacy in patients.

PMID- 16305285
TI  - Future in vitro and animal studies: development of pharmacokinetic and
      pharmacodynamic efficacy predictors for tissue-based antibiotics.
AB  - For antibiotics to exert their action on bacteria, both the bacteria and the drug
      need to be in the same place at the same time. The pharmacodynamics of
      antibiotics, measured as the ratio of area under the concentration-time
      curve:minimum inhibitory concentration (AUC:MIC), the ratio of plasma
      concentration:MIC, or time above MIC, indexes the pharmacokinetic properties of
      an antibiotic (in vivo) to a measure of microbiologic (antimicrobial) activity.
      Antimicrobial activity is measured as the MIC, and the pharmacokinetics generally
      used are those in the blood. However, if the infection is not in the blood but in
      some peripheral tissue such as the lung, it is the concentration of the drug in
      the lung that the pathogen sees, and thus the concentration in the blood (serum
      or plasma) is not important. Both in vitro and in vivo studies can aid in the
      development of pharmacodynamic parameters that characterize the drug-pathogen
      interaction, resulting in the determination of a dose or dosage regimen capable
      of curing an infection clinically.

PMID- 16305286
TI  - Infection site concentrations: their therapeutic importance and the macrolide and
      macrolide-like class of antibiotics.
AB  - Much confusion exists over the pharmacodynamics of macrolides, azalides, and
      ketolides, as the concentration-time profile for these agents is low relative to
      the minimum inhibitory concentration (MIC) of the pathogens for which they are
      used. Studies of respiratory tract infection have highlighted the importance of
      drug concentrations at the site of infection and have demonstrated a role for
      white blood cells in the delivery of drug to the infection site. Population
      mathematical modeling and Monte Carlo simulation have shown that the ability of
      macrolides, azalides, and ketolides to concentrate at the infection site has a
      considerable effect on microbial activity. Studies of the pharmacodynamics of
      these agents in animal models have centered on the mouse thigh model; however,
      the suitability of this model for investigation of respiratory tract infections
      for macrolides and macrolide-like drugs is questionable. Comparison of the mouse
      thigh model with the mouse lung model shows immediate discrepancies, such as a
      need for higher area under the concentration-time curve (AUC):MIC ratios in the
      mouse thigh. There are obvious failings in the use of a thigh model, as it does
      not take into account the accumulation of white blood cells in the epithelial
      lining fluid and therefore ignores the impact of white blood cell delivery to the
      site of infection and release of significant amounts of drug during phagocytosis.
      Ultimately, whereas the mouse pneumonia model is useful in identifying
      pharmacodynamically linked variables and the magnitude of variable required for a
      successful microbiologic outcome, extrapolation to human dosing must involve the
      use of human epithelial lining fluid penetration data.

PMID- 16305287
TI  - Pharmacodynamics and the prediction of efficacy in short-course antibiotic
      therapy: pediatric studies to validate the model.
AB  - Short-course antibiotic therapy for specific pediatric infections allows the
      clinician to minimize toxicities related to antibiotic exposure, to limit
      antibiotic resistance, and to improve compliance and cost without compromising
      microbiologic efficacy. Future studies of short-course therapy in children should
      address the pharmacokinetics of antibiotic exposure to the pathogen at the site
      of infection, the pharmacodynamics of pathogen eradication, and the many host
      factors involved in clinical and microbiologic outcomes. By using a mathematic
      model that integrates all important variables, one may be able to predict the
      probability of a cure with short-course therapy for each pathogen, antibiotic,
      site of infection, and host interaction.

PMID- 16305288
TI  - Clinical practice guidelines for bone metabolism and disease in chronic kidney
      disease: an overview.
AB  - The National Kidney Foundation developed and oversees the Kidney Disease Outcomes
      Quality Initiative, a process that develops clinical practice guidelines in
      nephrology. Recent guidelines address the aberrations in bone metabolism and
      disease that occur as a complication of chronic kidney disease. These guidelines
      provide, for the first time, a standard approach to the detection and management
      of alterations in calcium, phosphorus, and parathyroid hormone metabolism. The
      problems and sequelae of soft-tissue calcification are discussed, and
      recommendations are provided for reducing the associated morbidity and mortality.

PMID- 16305289
TI  - Absence of electrocardiographic findings and improved function with once-daily
      tiotropium in patients with chronic obstructive pulmonary disease.
AB  - STUDY OBJECTIVES: To examine electrocardiographic findings after short- and long
      term tiotropium therapy in patients with chronic obstructive pulmonary disease
      (COPD), and to establish previously reported symptomatic efficacy. DESIGN:
      Randomized, double-blind, placebo-controlled, parallel-group study. SETTING:
      Twelve outpatient investigational centers in the United States. PATIENTS: One
      hundred ninety-six patients with COPD. INTERVENTIONS: Patients received either
      tiotropium 18 mug once/day or placebo, delivered by the HandiHaler device.
      MEASUREMENTS AND MAIN RESULTS: Electrocardiography (predose and 5 min postdose)
      and 24-hour Holter monitoring were performed at baseline and after 8 and 12 weeks
      of treatment with tiotropium 18 microg once/day or placebo. Efficacy measures
      (spirometry, global COPD ratings, scores on the EuroQol Health Questionnaire [EQ
      5D], albuterol inhaler as needed) were included to demonstrate that the study
      population exhibited the characteristic improvements observed in previous
      tiotropium studies. Mean baseline forced expiratory volume in 1 second (FEV1) was
      1.03 L. Mean changes in heart rate from baseline were similar in both groups. No
      differences were noted in the percentage of patients developing rhythm or
      conduction abnormalities detected with electrocardiography or Holter monitoring.
      Frequency of premature beats and mean maximal changes in PR, QRS, QT, QTcB, and
      QTcF intervals were similar in both groups. No patients developed new-onset QT or
      QTc intervals greater than 500 msec, and no differences were noted in the
      percentage of patients developing new QT prolongation less than 30 msec, 30-60
      msec, or greater than 60 msec. At 12 weeks, predose and postdose improvements in
      FEV1 were 184 and 265 ml, respectively, with tiotropium versus placebo (p<0.001).
      Physician and patient global COPD ratings and the EQ-5D visual analog scale
      scores were improved with tiotropium (p<0.05); as-needed albuterol was reduced by
      25% relative to placebo (p<0.05). CONCLUSION: Tiotropium provided spirometric and
      symptomatic benefits in patients with COPD and was not associated with evidence
      of electrocardiographic changes in heart rate, rhythm, QT intervals, or
      conduction.

PMID- 16305290
TI  - Absence of QTc-interval-prolonging or hemodynamic effects of a single dose of
      bitter-orange extract in healthy subjects.
AB  - STUDY OBJECTIVE: To evaluate the hemodynamic and electrocardiographic effects of
      a single dose of commercially available bitter-orange dried-fruit extract, which
      is increasingly being used in dietary supplements. DESIGN: Randomized, double
      blind, placebo-controlled, crossover study. SETTING: University of Connecticut,
      Storrs Campus. SUBJECTS: Eighteen healthy volunteers aged 18 years or older.
      INTERVENTION: Subjects were given either placebo or bitter-orange dried-fruit
      extract (450 mg standardized to 27 mg of m- or p-synephrine) in phase 1. The
      opposite treatment was given during phase 2 after a washout period of at least 7
      days. MEASUREMENTS AND MAIN RESULTS: The rate-corrected QT (QTc) interval and
      blood pressure were measured before dosing and at 1, 3, 5, and 8 hours after
      dosing. Mean+/-SD values of the maximum postdose values were compared between
      groups. Subjects receiving bitter-orange extract versus those receiving placebo
      had similar postdose QTc intervals (402+/-29 vs 403+/-24 msec, p=0.653), systolic
      blood pressure (114+/-10 vs 115+/-8 mm Hg, p=0.686) and diastolic blood pressure
      (68+/-9 vs 68+/-8, p=0.879). CONCLUSION: Bitter-orange dried-fruit extract
      standardized to m- or p-synephrine 27 mg did not significantly alter the QTc
      interval or blood pressure after a single dose was administered. Future studies
      are necessary to ensure the safety of this herbal product with multiple doses.

PMID- 16305291
TI  - Effect of high-dose vitamin C on hepatic cytochrome P450 3A4 activity.
AB  - STUDY OBJECTIVES: To investigate the effect of high-dose vitamin C on cytochrome
      P450 (CYP) 3A4 activity, and to evaluate possible sex-specific effects on CYP3A4
      activity. DESIGN: Single-center longitudinal study. SETTING: Tertiary- and
      specialty-care teaching hospital. SUBJECTS: Fourteen healthy Caucasian adult
      volunteers (seven men, seven women). INTERVENTION: Subjects self-administered
      vitamin C 500 mg twice/day for 14 days. MEASUREMENTS AND MAIN RESULTS: Hepatic
      CYP3A4 activity was measured by using the erythromycin breath test on days 1
      (baseline) and 15. Overall, no significant effect of vitamin C on CYP3A4 activity
      was observed. Sex and baseline results were significant predictors of changes in
      CYP3A4 activity. In men, mean activity increased by 21.9% (95% confidence
      interval -3.88-47.6%). The effect in women was not consistent. CONCLUSION: Sex
      and baseline CYP3A4 activity appeared to influence the effect of vitamin C on
      CYP3A4 activity.

PMID- 16305292
TI  - Decreased persistence to cholinesterase inhibitor therapy with concomitant use of
      drugs that can impair cognition.
AB  - STUDY OBJECTIVES: To assess persistence with cholinesterase inhibitor therapy 6
      months after the start of treatment, and to determine whether the likelihood of
      persistence is associated with the coprescription of drugs that can impair
      cognition. DESIGN: Retrospective cohort study. SETTING: Community (home
      residence) or long-term care facility. PATIENTS: A total of 1183 patients
      enrolled in the Rhode Island Medicaid program, aged 45 years or older, who were
      dispensed a cholinesterase inhibitor from January 1, 2000-June 30, 2002.
      MEASUREMENTS AND MAIN RESULTS: Patients were considered persistent with treatment
      if they filled at least five prescriptions for a 1-month supply of the same
      cholinesterase inhibitor, without an extended gap in days between refills. We
      compared rates of persistence among patients receiving and those not receiving
      drugs that can impair cognition. Covariates assessed were patient age, sex, race,
      and care setting. Approximately one in four patients discontinued cholinesterase
      inhibitor therapy within 6 months. Patients aged 85 years or older were more
      persistent than younger patients (77% vs 71%, p<0.05). Caucasian patients were
      more likely to be persistent than non-Caucasian patients (74% vs 52%, p<0.001).
      Patients living in the community were less likely to persist than those residing
      in long-term care facilities (58% vs 76%, p<0.001). After adjusting for race and
      care setting, patients who were prescribed drugs that can impair cognition were
      more likely not to have persisted with cholinesterase inhibitor therapy at 6
      months than those who did not receive such drugs (odds ratio 1.56, 95% confidence
      interval 1.13-2.16). CONCLUSION: A substantial percentage of patients who began
      receiving cholinesterase inhibitor therapy had discontinued the therapy within 6
      months. Many patients also received prescriptions for agents that can impair
      cognition. Our findings indicated a modest but statistically significant increase
      in likelihood of treatment discontinuation among patients who also received
      prescriptions for drugs that can impair cognition. Iatrogenic causes of dementia
      are important to recognize and address so that therapies for enhancing cognition
      can be fully effective.

PMID- 16305293
TI  - Evaluation of diagnostic tests and argatroban or lepirudin therapy in patients
      with suspected heparin-induced thrombocytopenia.
AB  - STUDY OBJECTIVES: To evaluate diagnostic tests for heparin-induced
      thrombocytopenia (HIT), a serious drug reaction that can occur in patients
      receiving heparin, and to evaluate treatment with direct thrombin inhibitors-the
      only initial drug therapy that decreases the risk of thromboembolism associated
      with immune-mediated HIT. DESIGN: Retrospective cohort study. SETTING: University
      teaching hospital. SUBJECTS: Patients with HIT treated with argatroban or
      lepirudin between January 1, 2000, and December 31, 2003. MEASUREMENTS AND MAIN
      RESULTS: Patients were assessed for dosage and duration of argatroban or
      lepirudin therapy, HIT diagnostic tests, and clinically significant adverse
      events. Thirty-four patients received argatroban, 42 received lepirudin. Mean+/
      SD doses of argatroban and lepirudin were 1.2+/-0.9 microg/kg/minute and 0.09+/
      0.11 mg/kg/hour, respectively; both were 40% lower than the recommended doses.
      Mean duration of therapy was 10+/-9 days. Supratherapeutic activated partial
      thromboplastin times were observed in 30 (39%), 10 (13%) , and six (8%) of 76
      patients on days 1, 2, and 3, respectively (p<0.0001). Clinically significant
      bleeding occurred in 6% of patients receiving argatroban and in 5% of those
      receiving lepirudin (p=0.99); all patients had an activated partial
      thromboplastin time of longer than 100 seconds. Although platelet-aggregation
      tests were ordered in 55 (72%) of 76 patients, they were not useful in 16 (29%)
      because of equivocal or contradictory results. CONCLUSION: Due to
      supratherapeutic activated partial thromboplastin times, our patients often
      required doses of argatroban and lepirudin lower than those usually recommended.
      Thus, direct thrombin inhibitors should be started at low initial doses and
      titrated to target activated partial thromboplastin times to achieve appropriate
      efficacy and to avoid increasing the risk of bleeding. Platelet-aggregation tests
      were least useful for evaluating HIT. Appropriate diagnostic strategies should be
      used to avoid unnecessary drug use.

PMID- 16305294
TI  - Low-dose vitamin K to augment anticoagulation control.
AB  - STUDY OBJECTIVES: To determine the effect of daily low-dose oral vitamin K
      supplementation on reducing variations in the international normalized ratios
      (INRs) in patients taking warfarin. DESIGN: Retrospective analysis. SETTING:
      Anticoagulation clinic in a large, private-practice hematology group. PATIENTS:
      Eight motivated patients (three men, five women), aged 45-79 years, receiving
      anticoagulant therapy with warfarin, whose INRs had been fluctuating for reasons
      not associated with identifiable changes in diet, warfarin dosage, activity
      level, illness, or changes in drug therapy. INTERVENTION: Daily supplementation
      with oral vitamin K, starting with 100 microg/day MEASUREMENTS AND MAIN RESULTS:
      Anticoagulation providers monitored INR responses; all documented INR values were
      included in the analysis, even those intentionally allowed outside the
      therapeutic range when dosages were adjusted for procedures. After dietary
      vitamin K supplementation, INR fluctuations diminished in nearly all patients.
      Overall, a significant decrease was noted in the INR standard deviation (p<0.05),
      and more INRs were in the therapeutic range after the start of supplementation.
      Allowing for small fluctuations on either side of the target range, the number of
      INRs within 0.2 units of the target range increased from 32% to 57% (relative
      increase 76%). Time in range also increased by a similar degree. CONCLUSION:
      Supplementation with daily low-dose oral vitamin K significantly increased the
      number of INRs in range as well as the time in range, and decreased INR
      fluctuation in this small series of selected patients.

PMID- 16305295
TI  - Asthma-related health care resource use among patients starting fluticasone or
      montelukast therapy.
AB  - STUDY OBJECTIVES: To compare patterns of asthma-related health care resource use
      among patients prescribed fluticasone or montelukast as singlecontroller therapy
      for asthma, and to confirm patterns previously observed in retrospective analyses
      examining outcomes among patients receiving fluticasone or montelukast for
      asthma. DESIGN: Retrospective cohort study. DATA SOURCE: Administrative claims
      data drawn from United States health insurers in 35 states, covering 17 million
      privately insured patients. PATIENTS; A total of 4758 patients aged 2-55 years
      with asthma who were prescribed either fluticasone or montelukast from July 1,
      1998-June 30, 1999, were continuously enrolled for at least 24 months, had no
      evidence of controller therapy for 6 months before the start of drug therapy, and
      had no evidence of chronic obstructive pulmonary disease or other respiratory
      illness. MEASUREMENTS AND MAIN RESULTS: Patients were identified using an
      algorithm based on medical and pharmacy insurance claims. Patients were matched
      between groups based on a propensity score of clinical characteristics and age;
      this resulted in 1512 patients/treatment group. Asthma-related health care claims
      incurred for 12 months before and after the start of controller therapy were
      analyzed. After adjustment, the fluticasone-treated group had greater risk than
      the montelukast-treated group of requiring therapy with a short-acting beta
      agonist in the follow-up period (relative risk 1.12, 95% confidence interval [CI]
      1.03-1.20). Odds were similar across treatment groups for needing an emergency
      department visit and/or hospitalization (odds ratio 1.08, 95% CI 0.74-1.58) and
      for needing therapy with an oral corticosteroid (odds ratio 1.02, 95% CI 0.84
      1.26). CONCLUSION: The start of therapy with either fluticasone or montelukast as
      a single-controller for asthma was associated with similar asthma-related health
      care resource use in this matched population.

PMID- 16305296
TI  - Pharmacotherapy for human immunodeficiency virus-associated nephropathy.
AB  - Approximately 10% of adult patients with human immunodeficiency virus (HIV)
      infection have HIV-associated nephropathy (HIVAN). This condition, a leading
      cause of renal failure, is characterized by damage to specific areas of the renal
      filtration system. It manifests with increased serum creatinine levels, overt
      proteinuria, and in some patients, end-stage renal disease (ESRD). The mortality
      rate for HIVAN-related ESRD is high-30% within the first year of onset. Most
      instances of HIVAN occur in patients of African descent. Although advances in
      defining the pathology have been made, the optimal treatment strategy remains
      unclear. Potential benefits of potent combination antiretroviral therapy,
      angiotensin-converting enzyme (ACE) inhibitors, and corticosteroids have been
      reported in small clinical trials and case reports. Cyclosporine is another
      option, but clinical experience with this agent in managing HIVAN is limited. Few
      conclusions can be drawn from the limited body of available evidence.
      Antiretroviral therapy, ACE inhibitors, and corticosteroids are possibly
      associated with reversal of serum creatinine level increases and proteinuria, but
      studies are necessary to further define the role of these agents in therapy.
      Close monitoring is advised when treating any patient with HIVAN.

PMID- 16305297
TI  - Inhalation anesthesiology and volatile liquid anesthetics: focus on isoflurane,
      desflurane, and sevoflurane.
AB  - Clinical pharmacists rarely are involved in the selection and dosing of
      anesthetic agents. However, when practicing evidence-based medicine in a cost
      conscious health care system, optimizing drug therapy is imperative in all areas.
      Thus, we provide general information on anesthesiology, including the different
      types of breathing systems and the components of anesthesia machines. Modern
      inhalation anesthetics that are predominantly used in clinical practice include
      one gas--nitrous oxide--and new volatile liquid agents--isoflurane, desflurane,
      and sevoflurane. Desflurane and sevoflurane are the low-soluble inhalation
      anesthetics, and they offer some clinical advantages over isoflurane, such as
      fast induction and faster recovery with long procedures. However, efficient use
      of isoflurane can match the speed of induction and recovery of the other agents
      in certain cases. In addition, the patient characteristics, duration and type of
      procedure, type of breathing system, and efficiency in monitoring must be
      considered when selecting the most optimal therapy for each patient. Maximizing
      the clinical advantages of these agents while minimizing the waste of an
      institution's operating room and pharmacy budget requires an understanding of the
      characteristics, pharmacokinetics, and pharmacodynamics of these anesthetic
      agents and the collaborated effort from both the anesthesia and pharmacy
      departments. An anesthetic agent algorithm is provided as a sample decision
      process tree for selecting among isoflurane, desflurane, and sevoflurane.

PMID- 16305298
TI  - An approach to evaluating drug-nutrient interactions.
AB  - Although the significance of interactions between drugs is widely appreciated,
      little attention has been given to interactions between drugs and nutrients.
      Pharmacists are challenged to remember documented interactions involving
      available drugs, and they face the possibility that each newly approved
      therapeutic agent may be involved not only in unrecognized drug-drug interactions
      but in drug-nutrient interactions as well. A more consistent approach to
      evaluating drug-nutrient interactions is needed. The approach must be systematic
      in order to assess the influence of nutritional status, food, or specific
      nutrients on a drug's pharmacokinetics and pharmacodynamics, as well as the
      influence of a drug on overall nutritional status or on the status of a specific
      nutrient. We provide such a process, using several recently approved drugs as
      working examples. Risk factors and clinical relevance are described, with
      distinctions made between documented and potential interactions. Application of
      this process by the pharmacist to any drug will help increase their expertise.
      Furthermore, full consideration by pharmacists of all possible interactions of
      the drug regimens used in practice can allow for improved patient care.

PMID- 16305299
TI  - Predictors of noncompliance with warfarin therapy in an outpatient
      anticoagulation clinic.
AB  - STUDY OBJECTIVES: To test variables associated with the Health Belief Model, the
      Patient Satisfaction Model, and patient demographics in predicting compliance
      with warfarin therapy. DESIGN: Descriptive study using chart and pharmacy
      database review as well as patient questionnaires. SETTING: Outpatient
      anticoagulation clinic in an academic medical center. PATIENTS: Seventy-five
      patients who had received warfarin therapy over the previous 6 months.
      MEASUREMENTS AND MAIN RESULTS: Clinicians interviewed patients using a subscale
      of the Beliefs About Anticoagulation Survey and a Patient Satisfaction Model.
      Perceived barriers to compliance with warfarin therapy and marital status
      explained 21.7% of the variance in calculations of refill adherence (p<0.001).
      Compliance with warfarin therapy was assessed using a validated compliance self
      report survey and outpatient pharmacy dispensing data. Perceived barriers and
      current living conditions explained 33.2% of the variance in self-reported
      noncompliance (p<0.001). Logistic regression analysis, conducted to attempt to
      predict patients with an 80% refill adherence threshold, correctly classified
      compliance 85.3% of the time. CONCLUSION: This investigation provided some
      insight into the factors predictive of noncompliance in a low-income, outpatient
      population. Perceived barriers, marital status, living arrangements, and drug
      regimen played significant roles in warfarin noncompliance. Our results provide
      more evidence supporting the use of refill adherence and patient self-report as
      measures of noncompliance. This linkage helps validate compliance as a useful
      surrogate of patient health outcomes. This study also offers a model that can
      help clinicians identify patients at significant risk of noncompliant behavior.

PMID- 16305300
TI  - Effectiveness of pharmacist-administered diabetes mellitus education and
      management services.
AB  - STUDY OBJECTIVES: To evaluate the effectiveness of pharmacist-administered
      diabetes mellitus education and management services on selected diabetes
      performance measures. Additional goals were to compare outcomes with goals
      specified for patients with diabetes by the National Committee for Quality
      Assurance (NCQA) and identify areas for improvement. DESIGN: One-year
      observational study. SETTING: Three university-based primary care clinics.
      PATIENTS: One hundred ninety-one patients with diabetes. Intervention. Pharmacist
      provided diabetes education and management services. MEASUREMENTS AND MAIN
      RESULTS: Each patient was assessed for hemoglobin A1c (A1C) values, blood
      pressure, low-density lipoprotein cholesterol (LDL) levels, and aspirin use at
      baseline and at 1 year after enrollment. Cost avoidance comparators were
      calculated for those patients with reductions in A1C of at least 1%. Average A1C
      at 1 year was 7.8% (range 4.5-13.9%) versus 9.5% (range 5.4-19%) at baseline
      (change -1.7%, p<0.05). Seventy-two patients (38%) experienced a 1% or greater
      reduction in A1C. Average blood pressure decreased over the study period from
      141/79 to 135/75 mm Hg (p=0.007), but average LDL levels did not change to a
      statistically significant extent (114 to 112 mg/dl, p>0.05). Aspirin use
      increased from 34% at baseline to 73% at 1 year (p<0.0001). The program achieved
      the A1C and LDL values required to qualify for NCQA diabetes recognition. Based
      on an estimated savings of $820 for each 1% decrease in A1C, cost avoidance was
      calculated as $59,040. CONCLUSION: Diabetes management services from clinical
      pharmacists achieved significant improvements in A1C values, blood pressure, and
      aspirin use. Continued efforts in diabetes education and management are needed to
      further improve clinical, economic, and humanistic outcomes.

PMID- 16305301
TI  - Gabapentin-induced neurologic toxicities.
AB  - Gabapentin is an antiepileptic drug approved for the treatment of postherpetic
      neuralgia and as adjunctive therapy for partial seizures. The drug has been shown
      to be safe and nontoxic. The current literature has limited reports of neurologic
      toxicity associated with gabapentin therapy in patients with or without renal
      dysfunction. We describe the case of a 75-year-old man with renal dysfunction who
      developed neurologic toxicity due to gabapentin accumulation. Future studies are
      warranted to confirm the neurologic adverse effects of gabapentin, including any
      additional risks in patients with renal dysfunction.

PMID- 16305302
TI  - Tumor lysis syndrome after bortezomib therapy for plasma cell leukemia.
AB  - Tumor lysis syndrome (TLS) is a manifestation of metabolic disturbances that can
      lead to severe treatment complications and ultimately life-threatening events.
      This syndrome has been reported in solid tumors but is more common in bulky,
      hyperproliferative malignancies. Tumor lysis syndrome in plasma cell malignancies
      is less common due to the low turnover rate of the malignant B cells. Bortezomib
      is the first proteasome inhibitor approved by the United States Food and Drug
      Administration as second- and third-line therapy for patients with relapsed
      multiple myeloma. We describe the case of a patient with plasma cell leukemia
      treated with bortezomib who developed TLS. Bortezomib was begun as single-agent
      therapy that resulted in the development of TLS after the third dose of the first
      cycle. Evaluation with the Naranjo Adverse Drug Reaction Probability Scale
      indicated a probable relationship between TLS and bortezomib in this patient.
      Patients receiving bortezomib may be at risk for TLS, especially if they have
      high tumor burden, rapidly proliferative disease, and unfavorable cytogenetics.

PMID- 16305303
TI  - Use of ankle brachial index screening for selecting patients for antiplatelet
      drug therapy.

PMID- 16305305
TI  - An interview with Jeffrey Price, M.D., PH.D. Interview by Vicki Glaser.

PMID- 16305307
TI  - Systems cell biology knowledge created from high content screening.
AB  - High content screening (HCS), the large-scale automated analysis of the temporal
      and spatial changes in cells and cell constituents in arrays of cells, has the
      potential to create enormous systems cell biology knowledge bases. HCS is being
      employed along with the continuum of the early drug discovery process, including
      lead optimization where new knowledge is being used to facilitate the decision
      making process. We demonstrate methodology to build new systems cell biology
      knowledge using a multiplexed HCS assay, designed with the aid of knowledge
      mining tools, to measure the phenotypic response of a panel of human tumor cell
      types to a panel of natural product-derived microtubule-targeted anticancer
      agents and their synthetic analogs. We show how this new systems cell biology
      knowledge can be used to design a lead compound optimization strategy for at
      least two members of the panel, (-)-laulimalide and (+)-discodermolide, that
      exploits cell killing activity while minimally perturbing the regulation of the
      cell cycle and the stability of microtubules. Furthermore, this methodology can
      also be applied to basic biomedical research on cells.

PMID- 16305306
TI  - Statistics of assay validation in high throughput cell imaging of nuclear factor
      kappaB nuclear translocation.
AB  - This report describes statistical validation methods implemented on assay data
      for inhibition of subcellular redistribution of nuclear factor kappaB (NF kappaB)
      in HeLa cells. We quantified cellular inhibition of cytoplasmic-nuclear
      translocation of NF kappaB in response to a range of concentrations of
      interleukin-1 (IL-1) receptor antagonist in the presence of IL-1alpha using eight
      replicate rows in each four 96-well plates scanned five times on each of 2 days.
      Translocation was measured as the fractional localized intensity of the nucleus
      (FLIN), an implementation of our more general fractional localized intensity of
      the compartments (FLIC), which analyzes whole compartments in the context of the
      entire cell. The NF kappaB antagonist assay (inhibition of IL-1- induced NF
      kappaB translocation) data were collected on a Q3DM (San Diego, CA) EIDAQtrade
      mark 100 high throughput microscopy system. [In 2003, Q3DM was purchased by
      Beckman Coulter Inc. (Fullerton, CA), which released the IC 100 successor to the
      EIDAQ 100.] The generalized FLIC method is described along with two-point
      (minimum-maximum) and multiple point titration statistical methods. As a ratio of
      compartment intensities that tend to change proportionally, FLIN was resistant to
      photobleaching errors. Two-point minimum-maximum statistical analyses yielded the
      following: a Z' of 0.174 with the data as n = 320 independent well samples; Z' by
      row data in a range of 0.393-0.933, with a mean of 0.766; by-plate Z' data of
      0.310, 0.443, 0.545, and 0.794; and by-plate means of columns Z' data of 0.879,
      0.927, 0.945, and 0.963. The mean 50% inhibitory concentration (IC50) for IL-1
      receptor antagonist over all experiments was 213 ng/ml. The combined IC50
      coefficients of variation (CVs) were 0.74%, 0.85%, 2.09%, and 2.52% for the four
      plates. Repeatability IC50 CVs were as follows: day to day 3.0%, row to row 8.0%,
      plate to plate 2.8%, and day to day 0.6%. The number of cells required for
      statistically resolvable differences in dose concentrations, plotted in a family
      of FLIN sigma/deltamicro (SD/range) curves and tabulated, demonstrated cell-by
      cell assay precision with our combined sigma/deltamicro = 0.32 that required
      approximately 10-fold fewer cells than in a previously reported NF kappaB assay
      with sigma/deltamicro = 1.52. To better understand the relationship between cell
      by-cell measurements and IC50 precision, 500 Monte Carlo simulations with varying
      cell-measurement SDs were used to explore three-, five-, seven-, and 11-point
      model titrations. The reductions in deltaIC50 90% confidence intervals from 11-
      to three-point titrations were 10-fold with the previously reported
      sigma/deltamicro = 1.52 and twofold with our sigma/deltamicro = 0.32. With these
      normalized parameters, this report provides a common statistical foundation,
      independent of the assay details, for evaluating the performance of imaging data
      on any instrument.

PMID- 16305308
TI  - Improving high-content-screening assay performance by using division-arrested
      cells.
AB  - As cell-based assays are used more commonly in robotic high-throughput compound
      screening, cells themselves have become critical reagents. Thus, it has become
      essential to produce cell reagents with high consistency and quality. We
      experimented with cells division-arrested with low-level mitomycin C treatment
      and demonstrate that they perform with better consistency than non-division
      arrested counterparts in high-content screening imaging assays. We propose that
      for cell-based screening, it is possible to uncouple the cell production process
      from the screening process. Cells can be produced en masse, treated to become
      irreversibly division-arrested, and cryopreserved. These "ready-to-use" reagents
      can be thawed, plated, and used in screening with improved consistency and
      convenience.

PMID- 16305309
TI  - Assessing the minimum number of data points required for accurate IC50
      determination.
AB  - Combinatorial chemistry technology has enabled the synthesis of large, targeted
      libraries consisting of a much higher ratio of pharmacologically active compounds
      than traditional compound archives. This has resulted in a higher number of
      compounds requiring follow-up characterisation in full 50% inhibitory
      concentration (IC50) curves after the preliminary screen. The aim of this study
      was to develop a new assay format and analysis protocol for IC50 determination
      from the minimum number of data points so that more information could be derived
      from a primary inhibition screen. Data points from existing 10-point IC50 curves
      were used retrospectively to test the accuracy of IC50 predictions derived from
      just one or two compound concentrations. Regression analysis showed that both
      methods were useful, although, as expected, two compound concentrations gave more
      accurate IC50 predictions. A final experimental data set comparing IC50 values
      derived from a two- and 10- point assay format gave highly comparable data (r2 =
      0.89). This study shows that it is possible to generate IC50 values from an
      appropriately designed primary inhibition screen using two compound
      concentrations, reducing the requirement for follow-up IC50 determinations.

PMID- 16305310
TI  - A fluorescence-based coupling reaction for monitoring the activity of recombinant
      human NAD synthetase.
AB  - NAD synthetase is responsible for the conversion of nicotinic acid adenine
      dinucleotide to nicotinamide adenine dinucleotide. This reaction provides a
      biosynthetic route of the coenzyme and, thus, a source of cellular reducing
      equivalents. Alterations in the oxidative reductive potential of the cell have
      been implicated as a contributing factor in many disease states. Thus, this
      enzyme represents a new class of potential drug targets, and, hence, our efforts
      were focused upon developing a robust assay for utilization in a high throughput
      screen. Toward that end, we describe a coupled enzyme assay format for the
      measurement of recombinant human NAD synthetase by employing lactate
      dehydrogenase in a cycling/amplification reaction linked ultimately to the
      fluorescence generation of resorufin from resazurin via diaphorase. We present
      kinetics of the reaction of NAD synthetase in the coupled assay format,
      optimization conditions, and inhibition of the reaction by gossypol
      [1,1',6,6',7,7'-hexahydroxy-3,3'-dimethyl-5,5'-bis(1-methylethyl)-[2,2'-
      binaphthalene]-8,8'-dicarboxaldehyde] and illustrate the robustness of the assay
      by demonstrating 384-well microtiter plate uniformity statistics. Collectively,
      our results show that the assay method is both robust and well suited for this
      class of enzymes involved in the NAD+ biosynthetic pathway.

PMID- 16305311
TI  - Drug discovery in the kinase inhibitory field using the Nested Chemical Library
      technology.
AB  - Kinase inhibitors are at the forefront of modern drug research, where mostly
      three technologies are used for hit-and-lead finding: high throughput screening
      of random libraries, three-dimensional structure-based drug design based on X-ray
      data, and focused libraries around limited number of new cores. Our novel Nested
      Chemical Library (NCL) (Vichem Chemie Research Ltd., Budapest, Hungary)
      technology is based on a knowledge base approach, where focused libraries around
      selected cores are used to generate pharmacophore models. NCL was designed on the
      platform of a diverse kinase inhibitory library organized around 97 core
      structures. We have established a unique, proprietary kinase inhibitory chemistry
      around these core structures with small focused sublibraries around each core.
      All the compounds in our NCL library are stored in a big unified Structured Query
      Language database along with their measured and calculated physicochemical and
      ADME/toxicity (ADMET) properties, together with thousands of molecular
      descriptors calculated for each compound. Biochemical kinase inhibitory assays on
      selected, cloned kinase enzymes for a few hundred NCL compound sets can provide
      sufficient biological data for rational computerized design of new analogues,
      based on our pharmacophore model-generating 3DNET4W QSPAR (quantitative structure
      property/activity relationships) approach. Using this pharmacophore modeling
      approach and the ADMET filters, we can preselect synthesizable compounds for hit
      and-lead optimization. Starting from this point and integrating the information
      from QSPAR, high-quality leads can be generated within a small number of
      optimization cycles. Applying NCL technology we have developed lead compounds for
      several validated kinase targets.

PMID- 16305312
TI  - In vitro, ex vivo, and in vivo methodological approaches for studying therapeutic
      targets of osteoporosis and degenerative joint diseases: how biomarkers can
      assist?
AB  - Although our approach to the clinical management of osteoporosis (OP) and
      degenerative joint diseases (DJD)-major causes of disability and morbidity in the
      elderly-has greatly advanced in the past decades, curative treatments that could
      bring ultimate solutions have yet to be found or developed. Effective and timely
      development of candidate drugs is a critical function of the availability of
      sensitive and accurate methodological arsenal enabling the recognition and
      quantification of pharmacodynamic effects. The established concept that both OP
      and DJD arise from an imbalance in processes of tissue formation and degradation
      draws attention to need of establishing in vitro, ex vivo, and in vivo
      experimental settings, which allow obtaining insights into the mechanisms driving
      increased bone and cartilage degradation at cellular, organ, and organism levels.
      When addressing changes in bone or cartilage turnover at the organ or organism
      level, monitoring tools adequately reflecting the outcome of tissue homeostasis
      become particularly critical. In this context, bioassays targeting the
      quantification of various degradation and formation products of bone and
      cartilage matrix elements represent a useful approach. In this review, a
      comprehensive overview of widely used and recently established in vitro, ex vivo,
      and in vivo set-ups is provided, which in many cases effectively take advantage
      of the potentials of biomarkers. In addition to describing and discussing the
      advantages and limitations of each assay and their methods of evaluation, we
      added experimental and clinical data illustrating the utility of biomarkers for
      these methodological approaches.

PMID- 16305315
TI  - Immunosuppression with either cyclosporine a or FK506 supports survival of
      transplanted fibroblasts and promotes growth of host axons into the transplant
      after spinal cord injury.
AB  - Fibroblasts that have been genetically modified to secrete neurotrophins can
      stimulate axonal regeneration, rescue injured neurons, and improve function when
      grafted into a spinal cord injury site. These grafts are usually allografts that
      require immunosuppression to prevent rejection. In this study, we compared the
      effects of two immunophilin-ligands (cyclosporine A [CsA] and FK506) that are
      used clinically to prevent transplant rejection on protection of grafted
      fibroblasts. As there are risks associated with prolonged immunosuppression, we
      compared the effects of 2 or 8 weeks of administration of these drugs, in
      combination with our standard methylprednisolone protocol, in animals that
      survived for 8 weeks, to determine whether a shorter course of immunosuppression
      would be effective. Outcome measures included fibroblast survival, infiltration
      of activated macrophages and microglia into the graft, final lesion size, and
      growth of host axons into the graft. The graft consisted of a Vitrogen matrix
      into which fibroblasts were suspended; the graft was placed into a C3/C4 lateral
      funiculus lesion. The fibroblasts were isolated from a transgenic strain of
      Fischer rats that produce the marker alkaline phosphatase (Fb/AP). This enabled
      us to track the grafted fibroblasts and to evaluate the extent of their survival.
      The grafted matrix filled the lesion cavity. The density of fibroblasts within
      the matrix differed according to treatment. Fibroblast survival was most robust
      in animals that received 8 weeks of immunophilin-ligand treatment. FK506
      supported greater Fb/AP survival than CsA. ED-1 immunostaining for activated
      microglia and macrophages showed an inverse correlation between AP
      immunoreactivity and the density of immune cells within the graft. Thus,
      prolonged administration of either FK506 or CsA was necessary for maximal
      fibroblast survival and for limiting the macrophage invasion of the graft. None
      of the FK506 or CsA protocols modified the size of the lesion, indicating that
      these immunophilin-ligands had little effect on secondary enlargement of the
      lesion and therefore little neuroprotective effect. Because immunophilin-ligands
      have been shown to be neurotrophic, we used RT-97 immunostaining for
      neurofilaments and calcitonin gene related protein (CGRP) staining for dorsal
      root axons to visualize axons that grew into the graft. Some axons grew into the
      matrix even in the absence of immunophilin-ligand treatment, suggesting that the
      Vitrogen matrix itself is permissive, but all of the immunophilin-ligand
      protocols were much more effective in eliciting axonal growth. Growth of axons
      into the transplants was equally increased by drug treatment for 2 or 8 weeks.
      Thus, both treatments improved fibroblast survival, diminished immune cell
      invasion, and promoted axonal growth, and a 2-week course of treatment with
      either immunophilin-ligand was as effective as 8 weeks in stimulating axonal
      growth.

PMID- 16305316
TI  - Autologous olfactory glial cell transplantation is reliable and safe in naturally
      occurring canine spinal cord injury.
AB  - Intraspinal transplantation of olfactory glial cells (OGC) has produced well
      defined beneficial effects in experimental rodent models of spinal cord injury
      (SCI) and therefore has considerable promise as a treatment for severe SCI in
      human patients. In this study, we used clinical canine cases of severe SCI to
      determine whether derivation and transplantation of OGC from an autologous source
      was feasible. From the nerve fiber layer of a single olfactory bulb, we were able
      to generate 5 x 10(6) cells from each patient within 3 weeks. Of this population,
      72% were p75(+) OGC, 20% were meningeal cells, and the remainder mainly
      astrocytes. Intraspinal transplantation was not associated with any observable
      long- or short-term complications.

PMID- 16305317
TI  - Head position and impact direction in whiplash injuries: associations with MRI
      verified lesions of ligaments and membranes in the upper cervical spine.
AB  - In the present study, we compared magnetic resonance imaging (MRI) findings of
      soft tissue structures in the upper cervical spine between whiplash-associated
      disorder (WAD) patients and population-based control persons, and examined
      whether MRI-verified abnormalities in WAD patients were related to accident
      related factors hypothesized to be of importance for severity of injury. A total
      of 92 whiplash patients and 30 control persons, randomly drawn, were included.
      Information on the accident-related factors (i.e., head position and impact
      direction) was obtained by a questionnaire that was answered within 1 week after
      the accident. The MRI examination was performed 2-9 (mean 6) years after the
      accident. Focus was on MRI abnormalities of the alar and the transverse
      ligaments, and the tectorial and posterior atlanto-occipital membranes, graded 0
      3. For all neck structures, the whiplash patients had more high-grade lesions
      (grade 2 or 3) than the control persons (Chi-square test, p < 0.055). An abnormal
      alar ligament was most common (66.3% graded 2 or 3). Whiplash patients who had
      been sitting with their head/neck turned to one side at the moment of collision
      more often had high-grade lesions of the alar and transverse ligaments (p <
      0.001, p = 0.040, respectively). Severe injuries to the transverse ligament and
      the posterior atlanto-occipital membrane were more common in front than in rear
      end collisions (p < 0.001, p = 0.001, respectively). In conclusion, the
      difference in MRI-verified lesions between WAD patients and control persons, and
      in particular the association with head position and impact direction at time of
      accident, indicate that these lesions are caused by the whiplash trauma.

PMID- 16305318
TI  - Ventricular enlargement after moderate or severe head injury: a frequent and
      neglected problem.
AB  - The primary goal of this study was to determine the incidence of post-traumatic
      ventriculomegaly (Evans' index > or = 0.30) in 95 head-injured patients with a
      Glasgow Coma Scale (GCS) score of < or =13 at admission. Additional objectives
      were to determine the relationship between an increase in ventricular size and
      several clinical and radiological features and outcome. A planimetric study was
      carried out in the sequential control computed tomography (CT) scans of 34
      moderately head-injured (GCS 9-13) and 61 severely head-injured (GCS 3-8)
      patients with a minimum follow-up of 2 months. Between two and six CT scans were
      evaluated in each patient. The presence of subarachnoid hemorrhage (SAH) was
      registered. Evans' index was determined in all CT scans. In the final CT scan of
      each patient, ventricular size was related to the admission GCS score, age, the
      presence of SAH in the initial CT scans, type of brain lesion (classified
      according to the final diagnosis in the Traumatic Coma Data Bank classification),
      and outcome. Ventriculomegaly was found in 39.3% of patients with severe head
      injury and in 27.3% of those with a moderate head injury. Increased ventricular
      size was evident 4 weeks after injury in 57.6% and 2 months after injury in
      69.7%. No relationship was found between post-traumatic ventriculomegaly and age,
      initial GCS score, the presence of SAH, or type of lesion (focal or diffuse).
      Post-traumatic ventriculomegaly was significantly correlated with outcome. Post
      traumatic ventriculomegaly is a frequent and early finding in patients with
      moderate or severe traumatic brain injury.

PMID- 16305319
TI  - Role of decompressive surgery in the management of severe head injuries:
      prognostic factors and patient selection.
AB  - Decompressive surgery or craniectomy (DC) is a treatment option, which should be
      considered when the intracranial pressure (ICP) cannot be treated by conservative
      methods. The purpose of this study was to evaluate the benefits of decompressive
      craniectomy in patients with intractable posttraumatic intracranial hypertension
      and to evaluate the patient selection criteria for this management protocol. In
      this study, 100 patients with severe head injuries were involved. All patients
      were treated according to the European Brain Injury Consortium (EBIC) guidelines
      for severe head injuries and were assessed based on individual initial Glasgow
      Coma Scores (GCS), age, Glasgow Outcome Score (GOS), presence of systemic injury,
      changes in ICP, presence of mass lesion and the right timing for DC. All patients
      presented with a GCS of 8 or below. Based on their initial GCS, the patients were
      divided in two groups of 60 (group I with GCS 4-5) and 40 (group II with GCS 6-8)
      in each, respectively. Prognosis was evaluated according to the (GOS). After
      treatment with DC, 84 of the patients (84%) showed unfavorable and 16 (16%)
      showed favorable outcomes. In group I, 58 patients (96.6%) showed unfavorable and
      two (3.4%) showed favorable outcomes. In group II, 26 (65%) patients showed
      unfavorable and 14 (25%) showed favorable outcomes. The importance of initial GCS
      and age in patient outcomes were statistically significant. The presence of
      systemic injuries or mass lesions in outcomes were not statistically significant.
      Based on our findings, we conclude that patients with Glasgow Coma Scores of 6-8
      are the best candidates for DC treatment.

PMID- 16305320
TI  - Functional outcome scales in traumatic brain injury: a comparison of the Glasgow
      Outcome Scale (Extended) and the Functional Status Examination.
AB  - Clinical trials aimed at developing therapies for traumatic brain injury (TBI)
      require outcome measures that are reliable, validated, and easily administered.
      The most widely used of these measures, the Glasgow Outcome Scale (GOS) and the
      GOS-Extended (GOS-E), have been criticized as suffering from ceiling effects. In
      an attempt to develop a more useful and dynamic outcome measure, the Functional
      Status Examination (FSE) was developed, which grades outcome across 10 functional
      domains. The FSE has been demonstrated to be reliable and sensitive in monitoring
      recovery after TBI. This manuscript compares FSE with GOS-E in a cohort of
      patients with a wide range of injury severities. 177 individuals who survived at
      least 6 months after TBI were studied. The FSE and GOS-E were administered 6-12
      months after injury. FSE and GOS-E scores correlated well with each other. FSE
      scores were distributed throughout the range, indicating that ceiling and floor
      effects were not present. Physiologic measures of injury severity (Glasgow Coma
      Score [GCS]) did not correlate with anatomic measures (Abbreviated Injury Scale
      [AIS] and Injury Severity Score [ISS]). GCS correlated weakly with both outcome
      measures, but AIS/ISS did not. We conclude that FSE and GOS-E are reliable
      outcome measures for TBI survivors, and FSE may offer some advantages over GOS-E
      due its ability to provide a more detailed description of deficits. The majority
      of the variance in outcome is not accounted for by currently available measures
      of injury severity.

PMID- 16305321
TI  - Physician knowledge of the Glasgow Coma Scale.
AB  - Appropriate triage is critical to optimizing outcome from battle related
      injuries. The Glasgow Coma Scale (GCS) is the primary means by which combat
      casualties, who have suffered head injury, are triaged. For the GCS to be
      reliable in this critical role, it must be applied accurately. To determine the
      level of knowledge of the GCS among military physicians with exposure and/or
      training in the scale we administered a prospective, voluntary, and anonymous
      survey to physicians of all levels of training at military medical centers with
      significant patient referral base. The main outcome measures were correct
      identification of title and categories of the GCS along with appropriate scoring
      of each category. Overall performance on the survey was marginal. Many were able
      to identify what "GCS" stands for, but far fewer were able to identify the titles
      of the specific categories, let alone identify the specific scoring of each
      category. When evaluated based on medical specialties, those in surgical
      specialties outperformed those in the medical specialties. When comparing the
      different levels of training, residents and fellows performed better than
      attending staff or interns. Finally, those with Advanced Trauma Life Support
      (ATLS) certification performed significantly better than those without the
      training. Physician knowledge of the GCS, as demonstrated in this study, is poor,
      even in a population of individuals with specific training in the use of the
      scale. It is concluded that, to optimize outcome from combat related head injury,
      methods for improving accurate quantitation of neurologic state need to be
      explored.

PMID- 16305322
TI  - Temporal cavity and pressure distribution in a brain simulant following ballistic
      penetration.
AB  - To study ballistic brain injury biomechanics, two common civilian full metal
      jacket handgun projectiles (25-caliber and 9-mm) were discharged into a
      transparent brain simulant (Sylgard gel). Five pressure transducers were placed
      at the entry (two), exit (two) and center (one) of the simulant. High-speed
      digital video photography (20,000 frames/second) was used to capture the temporal
      cavity pulsation. Pressure histories and high-speed video images were
      synchronized with a common trigger. Pressure data were sampled at 308 kHz. The 25
      caliber projectile had an entry velocity of 238 m/s and exit velocity of 170 m/s.
      The 9-mm projectile had an entry velocity of 379 m/s and exit velocity of 259
      m/s. Kinetic energies lost during penetration were 45.2 J for the 25-caliber
      projectile and 283.7 J for the 9-mm. Size of temporary cavities and pressures
      were dependent on projectile size and velocity. The 9-mm projectile created
      temporary cavities 1.5 times larger in size and lasted 1.5 times longer than the
      25-caliber projectile. The 9-mm projectile had pressures three times higher than
      the 25-caliber projectile. Pressure differences between the center location and
      surrounding regions were approximately 1.4 times higher and lasted about 1.6
      times longer in the 9- mm projectile than the 25-caliber projectile. Collapsing
      of the temporary cavity drew the brain simulant toward the center of the
      temporary cavity and created negative pressures of approximately -0.5 atmospheric
      pressure in the surrounding region. Pressures reached approximately +2
      atmospheric pressure when temporary cavities collapsed. These quantified data may
      assist in understanding injury biomechanics and management of penetration brain
      trauma.

PMID- 16305323
TI  - Measurement of peripheral muscle resistance in rats with chronic ischemia-induced
      paraplegia or morphine-induced rigidity using a semi-automated computer
      controlled muscle resistance meter.
AB  - In experimental and clinical studies, an objective assessment of peripheral
      muscle resistance represents one of the key elements in determining the efficacy
      of therapeutic manipulations (e.g. pharmacological, surgical) aimed to ameliorate
      clinical signs of spasticity and/or rigidity. In the present study, we
      characterize a newly developed limb flexion resistance meter which permits a semi
      automated, computer-controlled measurement of peripheral muscle resistance (PMR)
      in the lower extremities during a forced flexion of the ankle in the awake rat.
      Ischemic paraplegia was induced in Sprague-Dawley rats by transient aortic
      occlusion (10 min) in combination with systemic hypotension (40 mm Hg). After
      ischemia the presence of spasticity component was determined by the presence of
      an exaggerated EMG activity recorded from gastrocnemius muscle after nociceptive
      or proprioceptive afferent activation and by velocity-dependent increase in
      muscle resistance. Rigidity was induced by high dose (30 mg/kg, i.p.) of
      morphine. Animals with defined ischemic spasticity or morphine-induced rigidity
      were then placed into a plastic restrainer and a hind paw attached by a tape to a
      metal plate driven by a computer-controlled stepping motor equipped with a
      resistance transducer. The resistance of the ankle to rotation was measured under
      several testing paradigms: (i) variable degree of ankle flexion (40 degrees, 50
      degrees, and 60 degrees), (ii) variable speed/rate of ankle flexion (2, 3, and 4
      sec), (iii) the effect of inhalation anesthesia, (iv) the effect of intrathecal
      baclofen, (v) the effect of dorsal L2-L5 rhizotomy, or (vi) systemic naloxone
      treatment. In animals with ischemic paraplegia an increased EMG response after
      peripheral nociceptive or proprioceptive activation was measured. In control
      animals average muscle resistance was 78 mN and was significantly increased in
      animals with ischemic spasticity (981-7900 mN). In ischemic-spastic animals a
      significant increase in measured muscle resistance was seen after increased
      velocity (4 > 3 > 2 sec) and the angle (40 degrees > 50 degrees > 60 degrees) of
      the ankle rotation. In spastic animals, deep halothane anesthesia, intrathecal
      baclofen or dorsal rhizotomy decreased muscle resistance to 39-80% of
      pretreatment values. Systemic treatment with morphine induced muscle rigidity and
      corresponding increase in muscle resistance. Morphine-induced increase in muscle
      resistance was independent on the velocity of the ankle rotation and was reversed
      by naloxone. These data show that by using this system it is possible to
      objectively measure the degree of peripheral muscle resistance. The use of this
      system may represent a simple and effective experimental tool in screening new
      pharmacological compounds and/or surgical manipulations targeted to modulate
      spasticity and/or rigidity after a variety of neurological disorders such as
      spinal cord traumatic or ischemic injury, multiple sclerosis, cerebral palsy, or
      Parkinson's disease.

PMID- 16305324
TI  - Prohemorrhagic and bleeding time activities of recombinant tissue plasminogen
      activator, heparin, aspirin, and a glycoprotein IIb/IIIa antagonist.
AB  - Intracerebral hemorrhage (ICH) is the most serious side effect of antithrombotic
      agents, especially in cases of cerebrovascular disease. In the present study, we
      compared the exacerbation of ICH and prolongation of bleeding time (BT) in guinea
      pigs with recombinant tissue plasminogen activator (rt-PA), heparin, aspirin, and
      FK419, a novel nonpeptide platelet glycoprotein (GP) IIb/IIIa receptor
      antagonist. ICH was induced by injection of bacterial collagenase into the
      caudate nucleus; BT was measured with a Simplate R device. Neither heparin nor
      aspirin prolonged BT. In contrast, rt-PA at the highest dose used in the study
      did prolong BT, and FK419 caused a dose-dependent prolongation of BT. Moreover,
      rt-PA and heparin increased the degree of ICH in a dose-dependent manner, leading
      to death in more than half of the animals treated with higher doses of these
      drugs. These findings show that the prohemorrhagic mechanisms underlying the
      prolongation of BT differ from those in collagenase-induced ICH, and that the
      risk of an agent with antithrombotic effects potentiating hemorrhage in the
      collagenase-induced model of ICH more closely parallels that in stroke patients
      than does the effect of the agent on BT. The findings also suggest that
      antiplatelet agents, including FK419, may be safer than thrombolytic or
      anticoagulant agents for use in patients at risk for ICH, such as those with
      stroke or cerebral aneurysm.

PMID- 16305325
TI  - Quick, practical selection of effective seeds for homology search.
AB  - It has been observed that in homology search gapped seeds have better sensitivity
      than ungapped ones for the same cost (weight). In this paper, we propose a
      probability leakage model (a dissipative Markov system) to elucidate the
      mechanism that confers power to spaced seeds. Based on this model, we identify
      desirable features of gapped search seeds and formulate an extremely efficient
      procedure for seed design: it samples from the set of spaced seed exhibiting
      those features, evaluates their sensitivity, and then selects the best. The
      sensitivity of the constructed seeds is negligibly less than that of the
      corresponding known optimal seeds. While the challenging mathematical question of
      characterizing optimal search seeds remains open, we believe that our eminently
      efficient and effective approach represents a satisfactory solution from a
      practitioner's viewpoint.

PMID- 16305326
TI  - A Fourier characteristic of coding sequences: origins and a non-Fourier
      approximation.
AB  - The 3-base periodicity, identified as a pronounced peak at the frequency N/3 (N
      is the length of the DNA sequence) of the Fourier power spectrum of protein
      coding regions, is used as a marker in gene-finding algorithms to distinguish
      protein coding regions (exons) and noncoding regions (introns) of genomes. In
      this paper, we reveal the explanation of this phenomenon which results from a
      nonuniform distribution of nucleotides in the three coding positions. There is a
      linear correlation between the nucleotide distributions in the three codon
      positions and the power spectrum at the frequency N/3. Furthermore, this study
      indicates the relationship between the length of a DNA sequence and the variance
      of nucleotide distributions and the average Fourier power spectrum, which is the
      noise signal in gene-finding methods. The results presented in this paper provide
      an efficient way to compute the Fourier power spectrum at N/3 and the noise
      signal in gene-finding methods by calculating the nucleotide distributions in the
      three codon positions.

PMID- 16305327
TI  - Pseudo-likelihood analysis of codon substitution models with neighbor-dependent
      rates.
AB  - Recently, Markov processes for the evolution of coding DNA with neighbor
      dependence in the instantaneous substitution rates have been considered. The
      neighbor dependency makes the models analytically intractable, and previously
      Markov chain Monte Carlo methods have been used for statistical inference. Using
      a pseudo-likelihood idea, we introduce in this paper an approximative estimation
      method which is fast to compute. The pseudo-likelihood estimates are shown to be
      very accurate, and from analyzing 348 human-mouse coding sequences we conclude
      that the incorporation of a CpG effect improves the fit of the model
      considerably.

PMID- 16305328
TI  - Algorithms for selecting informative marker panels for population assignment.
AB  - Given a set of potential source populations, genotypes of an individual of
      unknown origin at a collection of markers can be used to predict the correct
      source population of the individual. For improved efficiency, informative markers
      can be chosen from a larger set of markers to maximize the accuracy of this
      prediction. However, selecting the loci that are individually most informative
      does not necessarily produce the optimal panel. Here, using genotypes from eight
      species--carp, cat, chicken, dog, fly, grayling, human, and maize--this
      univariate accumulation procedure is compared to new multivariate "greedy" and
      "maximin" algorithms for choosing marker panels. The procedures generally suggest
      similar panels, although the greedy method often recommends inclusion of loci
      that are not chosen by the other algorithms. In seven of the eight species, when
      applied to five or more markers, all methods achieve at least 94% assignment
      accuracy on simulated individuals, with one species--dog--producing this level of
      accuracy with only three markers, and the eighth species--human--requiring
      approximately 13-16 markers. The new algorithms produce substantial improvements
      over use of randomly selected markers; where differences among the methods are
      noticeable, the greedy algorithm leads to slightly higher probabilities of
      correct assignment. Although none of the approaches necessarily chooses the panel
      with optimal performance, the algorithms all likely select panels with
      performance near enough to the maximum that they all are suitable for practical
      use.

PMID- 16305329
TI  - Evaluation of experimental designs for two-color cDNA microarrays.
AB  - The major goal of two-color cDNA microarray experiments is to measure the
      relative gene expression level (i.e., relative amount of mRNA) of each gene
      between samples in studies of gene expression. More specifically, given an N
      sample experiment, we need all N(N - 1)/2 relative expression levels of all
      sample pairs of each gene for identification of the differentially expressed
      genes and for clustering of gene expression patterns. However, the intensities
      observed from two-color cDNA microarray experiments do not simply represent the
      relative gene expression level. They are composed of signal (gene expression
      level), noise, and other factors. In discussions on the experimental design of
      two-color cDNA microarray experiments, little attention has been given to the
      fact that different combinations of test and control samples will produce
      microarray intensities data with varying intrinsic composition of factors. As a
      consequence, not all experimental designs for two-color cDNA microarray
      experiments are able to provide all possible relative gene expression levels.
      This phenomenon has never been addressed. To obtain all possible relative gene
      expression levels, a novel method for two-color cDNA microarray experimental
      design evaluation is necessary that will allow the making of an accurate choice.
      In this study, we propose a model-based approach to illustrate how the factor
      composition of microarray intensities changed with different experimental designs
      in two-color cDNA microarray experiments. By analyzing 12 experimental designs
      (including 5 general forms), we demonstrate that not all experimental designs are
      able to provide all possible relative gene expression levels due to the
      differences in factor composition. Our results indicate that whether an
      experimental design can provide all possible relative expression levels of all
      sample pairs for each gene should be the first criterion to be considered in an
      evaluation of experimental designs for two-color cDNA microarray experiments.

PMID- 16305330
TI  - Automatic 3D protein structure classification without structural alignment.
AB  - In this paper, we present a new scheme named ProtClass for automatic
      classification of three-dimensional (3D) protein structures. It is a dedicated
      and unified multiclass classification scheme. Neither detailed structural
      alignment nor multiple binary classifications are required in this scheme. We
      adopt a nearest neighbor-based classification strategy. We use a filter-and
      refine scheme. In the first step, we filter out the improbable answers using the
      precalculated parameters from the training data. In the second, we perform a
      relatively more detailed nearest neighbor search on the remaining answers. We use
      very concise and effective encoding schemes of the 3D protein structures in both
      steps. We compare our proposed method against two other dedicated protein
      structure classification schemes, namely SGM and CPMine. The experimental results
      show that ProtClass is slightly better in accuracy than SGM and much faster. In
      comparison with CPMine, ProtClass is much more accurate, while their running
      times are about the same. We also compare ProtClass against a structural
      alignment-based classification scheme named DALI, which is found to be more
      accurate, but extremely slow. The software is available upon request from the
      authors. The supplementary information on ProtClass method can be found at:
      http://xena1.ddns.comp.nus.edu.sg/ approximately genesis/PClass.htm.

PMID- 16305331
TI  - Stem cells: shibboleths of development, part II: Toward a functional definition.
AB  - Our previous discourse on stem cell characteristics led to the conclusion that
      the qualities deemed essential for a cell to be considered a "stem cell" are
      neither firmly established nor universally accepted, and this we accept as
      editorial policy. In that study, self-renewal, asymmetric division, phenotypic
      markers, and other attributes touted as being indicative of cells being stem
      cells were critically questioned as fundamental to the definition of a stem cell,
      leading us to seek a functional definition instead. Here, we offer further
      considerations, and elaborate on the characteristics that diverse investigators
      feel are essential for a cell to function as a stem cell, either in development
      or body maintenance. We hope that this discourse will promote further reflection,
      culminating with a definition that is widely accepted and universally applicable.
      We confess this goal has not been reached, neither here nor elsewhere. The
      outstanding goal of understanding what stem cells are, a prerequisite of
      characterizing what stem cells do and how they do it, is still outstanding.

PMID- 16305332
TI  - Three-dimensional structure prediction of the interaction of CD34 with the SH3
      domain of Crk-L.
AB  - The monomeric 115-kDa surface protein CD34, which is present on many stem cell
      populations, has been useful to enumerate the quality and viability of cell
      suspensions for engraftment. Although these studies assure the validity of CD34
      as a stem cell marker, the functional role of this molecule has not been defined.
      CD34 has been demonstrated to regulate adhesion, differentiation, and
      proliferation of hematopoietic stem cells and other progenitors. The cytoplasmic
      domain of CD34 is known to be essential for its function. However, it is not
      clear how this domain's interactions with other molecules support the functional
      activity of CD34. Here we show that the cytoplasmic tail of CD34 is structurally
      similar to the carboxyl terminus of the gap junction protein Connexin 43 (Cx43).
      Because the activity of CD34 is mediated through its interaction with an SH3
      domain of an intracellular protein, we attempted to define the SH3 binding region
      and amino acids involved in this interaction. We identified Glu325 to Ser334 as
      potential SH3 binding sites. Our results suggest that the interaction of the
      cytoplasmic tail of CD34 with the shallow proline-rich motif-binding groove of
      Crk-L is essential for the function of CD34 in stem cell development.

PMID- 16305334
TI  - Stable plasmid-based siRNA silencing of gene expression in human embryonic stem
      cells.
AB  - RNA interference (RNAi) using short inhibitory RNAs (siRNAs) has been widely
      explored for the suppression of cellular mRNA levels to investigate the function
      of specific genes, including gene function in differentiation and development.
      The establishment of human embryonic stem cell (hESC) models for differentiation
      of selected lineages is an area of intense interest and activity. On the basis of
      our previous work with stable overexpression of enhanced green fluorescent
      protein (EGFP) in hESC, we used plasmid vector-based siRNA expression to silence
      EGFP expression in stably-transfected hESC. After hygromycin selection, we
      derived several cell lines in which EGFP expression was significantly reduced. At
      the genomic DNA level, there was no difference between the two cell lines and the
      parental H1EGFP cell line when analyzed with quantitative PCR; however, there
      were significant differences among the three cell lines at the RNA and protein
      levels as analyzed with real-time RT-PCR and Western blotting. From these data,
      we conclude that the decrease in EGFP expression was caused by RNAi, not by
      genomic DNA loss. Down-regulation of EGFP expression was sustained through
      multiple passages of both siEGFP cell lines. This simple silencing system will
      allow novel investigations of target gene function in hESC self-renewal or
      differentiation, as well as differentiated function in other cell types.

PMID- 16305333
TI  - Hematopoietic stem cells give rise to perivascular endothelial-like cells during
      brain tumor angiogenesis.
AB  - Bone marrow (BM) cells have recently been shown to give rise to skeletal,
      hepatic, cardiac, neural, and vascular endothelial tissues. However, it has been
      shown that this is the result of cell fusion rather than transdifferentiation of
      hematopoietic stem cells (HSC). For this study, we established a mouse model of
      brain tumor growth to investigate the differentiation potential of HSC into
      endothelial cells during brain tumor-induced angiogenesis. Nontransgenic
      (GFP(neg)) recipient mice were lethally irradiated, and their hematopoietic cells
      were subsequently repopulated by transplantation of a single green fluorescent
      protein (GFP)-expressing HSC. Rat glioma (RT-2/RAG) cells were then injected into
      the striatum of the chimeric mice 6-8 weeks post-transplantation. The animals
      were sacrificed 3-9 days after tumor implantation, and the mobilization, temporal
      spatial distribution, and lineage-specific marker expression profile of the
      GFP(+) cells within the growing tumor were analyzed. We saw that GFP(+) cells
      gave rise to elongated, CD34(+)/Flk-1(+) cells that incorporated into the
      endothelium of tumor blood vessels. However, all GFP(+) cells were also CD45(+),
      and the presence of CD45 on the HSC-derived endothelial-like cells supports the
      hypothesis that the hematopoietic cells were recruited into the tumor milieu. The
      fact that we failed to demonstrate the expression of von Willebrand factor in
      these cells argues against a true endothelial identity. Nevertheless, the
      recruitment of HSC-derived endothelial-like cells was an extremely rare event in
      normal brain parenchyma, and, thus, the permissive influence afforded by the
      growing tumor appeared to enhance the perivascular tropism and acquisition of an
      endothelial phenotypes by a population of HSC-derived cells.

PMID- 16305335
TI  - Analysis of the human fetal liver hematopoietic microenvironment.
AB  - In the adult, hematopoietic stem cells (HSCs) are resident in the bone marrow
      (BM) compartment and are in direct association with the BM stromal
      microenvironment. However, human adult HSCs are largely quiescent and undergo
      limited self-renewal. This is in contrast to the higher frequency of cycling HSCs
      undergoing self-renewal during fetal development when hematopoiesis is
      transiently localized to the fetal liver (FL), suggesting that FL provides a more
      conducive microenvironment to support HSCs. Here, we provide phenotypic and
      molecular characterization of primary human FL stromal cells capable of
      supporting human repopulating progenitors. Qualitative and quantitative analysis
      revealed several properties unique to FL stromal cells compared to adult BM
      derived stroma that included a greater than 10-fold enhanced proliferative
      capacity of FL stromal vs adult BM, and a 2-fold increase in the number of N
      cadherin- and osteopontin-expressing cells. Supportive of extrinsic influences
      likely to modulate HSC expansion, global gene expression microarray analysis
      revealed that FL stroma has higher expression of regulators of the Wnt signaling
      pathway compared to adult BM stroma, which demonstrated an increased expression
      of the Notch signaling pathway. Our results suggest that human FL stromal cells
      provide a unique microenvironment to HSCs compared to adult BM stroma by
      controlling Wnt signaling of HSCs during human fetal hematopoietic development,
      while Notch signaling is tightly regulated by the HSC microenvironment in the
      adult. We propose that the human HSC niche is ontogenically controlled during
      human development to provide appropriate expansion of fetal HSCs and subsequent
      maintenance of adult HSCs.

PMID- 16305336
TI  - Osteopetrotic mouse stroma with thrombopoietin, c-kit ligand, and flk-2 ligand
      supports long-term mobilized CD34+ hematopoiesis in vitro.
AB  - OP-9 cells are stromal cells derived from macrophage colony-stimulating factor (M
      CSF)-deficient osteopetrotic mice. To evaluate the OP-9 capability to sustain
      long-term hematopoiesis, we reported the expansion of granulocyte colony
      stimulating factor (G-CSF)-mobilized human peripheral blood (PB) CD34(+) cells in
      co-culture with murine OP-9 and MS-5 stromal cells, either transfected with
      various combinations of adenovectors (Ad) expressing c-kit ligand (KL) (either
      soluble or transmembrane form), thrombopoietin (TPO), flt-3/flk2 ligand (FL), and
      granulocyte-macrophage (GM)-CSF or with weekly addition of these cytokines.
      Expression of TPO as well as association of TPO, FL, and KL increased progenitor
      cell and week-6 cobblestone area forming cell (CAFC) production in all stromal co
      cultures. Similar progenitor expansion was obtained by weekly addition of soluble
      cytokine. Five weeks of co-culture with OP9 and TPO, FL + KL resulted in the
      greatest expansion of progenitor cells and week-6 CAFC as measured by secondary
      assay on MS-5. In contrast to MS-5 and TPO or TPO + FL + KL cultures where
      hematopoiesis declined by week 4, progenitor as well as week-6 CAFC expansion
      continued for over 3 months in TPO + FL + KL OP9 cocultures. This was associated
      with decrease of CD14(+) macrophage production. The addition of human macrophage
      (M)-CSF or CD14(+) cells to the co-culture decrease progenitor and stem cell
      expansion; however, murine M-CSF to OP-9 co-cultures did not decrease progenitor
      expansion. High levels of stromal-derived factor-1 (SDF-1) production by MS-5 and
      low or absent production by OP-9 may account for stem cell adhesion and CAFC
      formation in the former cultures and the predominance of stem and progenitor
      cells in the nonadherent fraction in the latter cultures.

PMID- 16305337
TI  - NTera2: a model system to study dopaminergic differentiation of human embryonic
      stem cells.
AB  - NTera2, a human embryonal carcinoma (EC) stem cell line, shares many
      characteristics with human embryonic stem cells (hESCs). To determine whether
      NTera2 can serve as a useful surrogate for hESCs, we compared global gene
      expression between undifferentiated NTera2, multiple undifferentiated hESC cell
      lines, and their differentiated derivatives, and we showed that NTera2 cells
      share multiple markers with hESCs. Similar to hESCs, NTera2 cells differentiated
      into TH-positive cells that express dopaminergic markers including AADC, DAT,
      Nurr1, TrkB, TrkC, and GFRA1 when co-cultured with PA6 cells. Flow cytometry
      analysis showed that tyrosine hydroxylase (TH) and neural cell adhesion molecule
      (NCAM) expression increased, whereas SSEA4 expression decreased as cells
      differentiated. Medium conditioned by PA6 cells stimulated differentiation of
      NTera2 cells to generate TH-positive cells that expressed dopaminergic markers.
      Flow cytometry selected polysialylated (PSA-NCAM) cells responded to medium
      conditioned by PA6 cells by differentiating into TH-positive cells and expressed
      dopaminergic markers. Sorted cells differentiated for 4 weeks in PA6 cell
      conditioned media included functional neurons that responded to neurotransmitters
      and exhibited electronic excitability. Therefore, NTera2 cell dopaminergic
      neuronal differentiation and PSA-NCAM enrichment provides a useful system for the
      future study of hESCs.

PMID- 16305338
TI  - Identification of committed placental stem cell lines for studies of
      differentiation.
AB  - Trophoblasts provide a model to investigate fundamental mechanisms of stem cell
      differentiation, but the availability of trophoblast stem cell lines is limited.
      Here we report the development of an RT-PCR-based lineage-specific profile as a
      method to identify the lineages of placental trophoblast cells routinely and
      specifically. This profiling method was used to analyze the mouse SM10 and rat
      HRP-1 cell lines, isolated from a region of the placental labyrinth, but of
      previously unidentified lineage. Using this profile, the expression of
      trophoblast stem cell markers was detected in the SM10 and HRP-1 cells. In
      contrast, no expression of a marker of differentiated labyrinthine trophoblast
      was detected. Additionally, both cell lines expressed labyrinthine trophoblast
      specific genes and did not express lineage-specific markers of
      spongiotrophoblasts or trophoblast giant cells. Our results suggest that SM10 and
      HRP-1 cell lines are trophoblast stem cell-like cell lines that can be maintained
      in undifferentiated but committed state in cell culture. These cell lines express
      labyrinthine-specific genes and are committed to differentiate solely into
      functional labyrinthine trophoblasts. Our profiling method provides a new
      technique to identify stem cells and their lineage-specific differentiation. This
      method additionally indicates that SM10 and HRP-1 cell lines provide new systems
      for future studies of stem cell differentiation, allowing investigation of basic
      mechanisms of differentiation, which may provide insights into the biophysics of
      development of a specialized system. This method should also prove to be useful
      for identification of other stem cell lines and examination of lineage-specific
      commitment.

PMID- 16305339
TI  - Lactoferrin accelerates reconstitution of the humoral and cellular immune
      response during chemotherapy-induced immunosuppression and bone marrow transplant
      in mice.
AB  - Experimental evidence from previous studies supports the conclusion that orally
      administered lactoferrin (LF) restores the immune response in mice treated with a
      sublethal dose of cyclophosphamide (CP). The aim of this study was to elucidate
      potential benefit of LF in mice undergoing chemotherapy with busulfan (BU) and
      CP, followed by intravenous (i.v.) injection of bone marrow cells. CBA mice were
      treated orally with busulfan (4 mg/kg) for 4 consecutive days, followed by two
      daily doses of CP delivered intraperitoneally (i.p.) at a dose of 100 mg/kg and
      reconstituted next day with i.v. injection of 10(7) syngeneic bone marrow cells.
      One group of these mice was given LF in drinking water (0.5% solution). After
      treatment, mice were immunized with ovalbumin (OVA) to subsequently measure
      delayed type hypersensitivity responsiveness and with sheep red blood cells to
      determine humoral immunity by evaluation of splenic antibody-forming cells. As
      expected, both humoral and cellular immune responses of mice that were treated
      with these chemotherapeutic agents was markedly impaired. Here we report that
      this impairment was remarkably attenuated by oral administration of LF. Humoral
      immunity fell to levels that were 66-88% lower than that of untreated animals.
      Humoral immunity of LF-treated animals was equivalent to that of untreated mice
      within 1 month. Cellular immune responses were inhibited by chemotherapy
      treatment to a lesser degree, reaching levels that were approximately 50% lower
      than those of untreated animals. Again, LF mitigated this decrease, resulting in
      responses that were only slightly lower than those observed in untreated animals.
      Furthermore, when mice were given a lethal dose of BU (4 x 25 mg daily doses,
      i.p.) followed by a bone marrow transplant, LF caused enhanced lympho-, erythro-,
      and myelopoiesis in the bone marrow and appearance of transforming splenic
      lymphoblasts, similar to effects caused by administration of recombinant human
      granulocyte-macrophage colony-stimulating factor (GM-CSF). In summary, our study
      suggests that LF may be a useful agent to accelerate restoration of immune
      responsiveness induced by chemotherapy in bone marrow transplant recipients.

PMID- 16305340
TI  - The human orthologue of a novel apoptosis response gene induced during rat
      myelomonocytic stem cell apoptosis maps to 20q13.12.
AB  - Stem cell factor (SCF) stimulation of the receptor tyrosine kinase c-kit has
      effects on the proliferation, differentiation, and apoptotic regulation of
      hematopoietic progenitor cell populations. Rat bone marrow myelomonocytic stem
      cells (MSC) isolated in vitro by wheat germ agglutinin culture exclusively
      undergo self-renewal divisions when stimulated by SCF but bipotentially
      differentiate in the presence of dexamethasone or 1alpha,25-dihydroxyvitamin D(3)
      to granulocytes and macrophages, respectively. We show here that withdrawal of
      SCF from MSC induces rapid apoptosis in all stages of the cell cycle accompanied
      by development of an ultrastructural apoptotic morphology. To investigate
      immediate-early gene induction during MSC apoptosis, a differential display
      polymerase chain reaction (DD-PCR) screen coupled with rapid amplification of
      cDNA ends (RACE) PCR was performed. An immediate-early apoptosis response gene
      was isolated from growth factor-deprived MSC that was not expressed during self
      renewal or differentiation induction cultures containing SCF. The protein
      contains a PEST region enriched in proline, glutamic acid, serine, and threonine
      residues common to proteins with a high turnover and has a cytoplasmic, vesicular
      localization in apoptotic MSC shown by immunohistochemistry. The human
      orthologous gene, isolated by RACE PCR, shows 86% homology to the rat protein and
      high similarity with a human uncharacterized hypothalamus predicted protein
      (HSMNP1) localized to the long arm of chromosome 20. Because deletions in this
      region are a common occurrence in a wide range of myeloproliferative disorders
      characterized by treatment resistance to apoptosis, HSMNP1 expression may play a
      role in normal and pathological myeloid development.

PMID- 16305341
TI  - The rate of marrow recovery and extent of donor engraftment following
      transplantation of ex vivo-expanded bone marrow cells are independently
      influenced by the cytokines used for expansion.
AB  - Successful stem cell transplantation depends on cell dose, and this is
      particularly true for placental/cord blood transplantation in which it has been
      clearly shown that both the success of engraftment as well as the speed of white
      cell and platelet recovery are dependent on the nucleated cell dose in the graft.
      Thus, if stem cell numbers could be increased, the speed as well as the
      likelihood of engraftment might be improved. We studied the effect of two
      different cytokine combinations--kit ligand (KL), interleukin-3 (IL-3), and Flt-3
      ligand supplemented with thrombopoietin and IL-11 (combination 1) or
      granulocyte/macrophage colony-stimulating factor (GM-CSF) and G-CSF (combination
      2)--for their ability to affect speed and extent of engraftment using limited
      numbers (5 x 10(4)) of murine bone marrow (BM) light-density (LD) cells or their
      progeny expanded ex vivo in the presence one or the other cytokine combination
      for 6 days. With combination 1, we found that speed of platelet recovery was
      enhanced, but at the expense of white blood cell (WBC) recovery and percent donor
      engraftment. Furthermore, the cytokine combination that best maintained donor
      engraftment, combination 2, did so at the expense of platelet recovery. In no
      case was percent donor engraftment improved over 5 x 10(4) unmanipulated LD BM
      cells. These results are consistent with the interpretation that immediate
      recovery of blood cells of different lineages and longterm donor engraftment are
      separate functions that can be influenced by the choice of cytokines used during
      the ex vivo expansion process.

PMID- 16305342
TI  - Stroke-induced migration of human umbilical cord blood cells: time course and
      cytokines.
AB  - The therapeutic window for treatment of individuals after stroke is narrow,
      regardless of the treatment regime; extension of this window would provide a
      major therapeutic advance. In prior reports, we demonstrated significant
      improvements in the behavioral defects of rats that received human umbilical cord
      blood (HUCB) cells 24 h after a middle cerebral arterial occlusion. These effects
      paralleled the recruitment of these cells to the site of tissue damage. While the
      administration of HUCB cells 24 h after stroke was effective, the optimal time to
      administer these cells after stroke has not been established. Here, we
      investigated the migration of HUCB cells to ischemic tissue extracts. After
      ischemic assault, brain tissue was homogenized, and the supernatants were assayed
      for their ability to attract HUCB mononuclear cells as well as for levels of
      several cytokines. We demonstrate increased migratory activity of HUCB cells
      toward the extracts harvested at 24-72 h after stroke. The extracts possessed
      increased levels of certain cytokines and chemokines, suggesting their
      participation in HUCB cell migration. The results from this study are promising
      in that the current 3-h therapeutic window for the treatment of stroke victims,
      using approved anticoagulant treatment, may be extended with the use of HUCB cell
      therapy 24-72 h post stroke. Last, the chemokines present in the supernatant
      provide a sound starting point to start examining the mechanisms responsible for
      the in vivo migration of HUCB cells after the induction of stroke.

PMID- 16305343
TI  - Alteration on the expression of IL-1, PDGF, TGF-beta, EGF, and FGF receptors and
      c-Fos and c-Myc proteins in bone marrow mesenchymal stroma cells from advanced
      untreated lung and breast cancer patients.
AB  - Previously, we reported a deficient cloning capacity of the bone marrow (BM)
      mesenchymal stem cells to give colony-forming unit fibroblast (CFU-F) and an
      inefficient confluence capacity of BM stromal cells in advanced untreated lung
      cancer patients (LCP) and breast cancer patients (BCP). Moreover, a decreased
      level of bFGF at day 7 in the conditioned media from BM CFU-F cultures was found
      in both cancer groups when compared to the normal range. The current study was
      specially undertaken, to evaluate the percentage of subconfluent fibroblasts
      expressing receptors (R) of interleukin-1 (IL-1), platelet-derived growth factor
      (PDGF), fibroblast growth factor (FGF), transforming growth factor (TGF-beta),
      epidermal growth factor (EGF), and the proteins c-Fos and c-Myc in BM primary
      cultures from untreated LCP and BCP. An immunocytochemical study on subconfluent
      BM fibroblast cultures from 13 healthy patients, 16 LCP, and 8 BCP was performed,
      using as primary antibodies, anti-type I of IL-1 R (IL-1R-1), anti-alpha, beta
      chains of PDGF R (PDGFR-alpha, PDGFR-beta), anti-type I of FGF R (FGFR-I), anti
      type I, II, and III of TGF-beta R (TGF-betaR-I, TGF- betaR-II, and TGF-betaR
      III), anti-EGF R, anti-c-Fos, and anti-c-Myc. A diminished percentage of
      subconfluent fibroblasts expressing PDGFR-alpha, TGFbetaR-I, II, III, EGFR, and
      FGFR-I was found in LCP and BCP compared to healthy patients. A diminished
      percentage of subconfluent fibroblasts expressing c-Fos and c-Myc was found in
      patients when compared to healthy patients. The alterations we describe could
      help to explain the deficiency regarding the proliferative and confluence
      capacity of BM stroma cells in cancer patients.

PMID- 16305344
TI  - Anti-inflammatory effects of human cord blood cells in a rat model of stroke.
AB  - When human umbilical cord blood cells (HUCBCs) are administered intravenously
      after a middle cerebral artery occlusion, they reliably produce behavioral and
      anatomical recovery, and protect neural tissue from progressive change. However,
      our results indicate that the cells do not exert their effects by engraftment in
      the peri-infarct region, even though they migrate to the site of injury. The
      objective of the present study was to determine if the cells induce recovery by
      decreasing inflammation. We used a combination of in vivo and in vitro studies to
      show that HUCBCs decrease inflammation in the brain after stroke and thereby
      enhance neuroprotection. After stroke and transplantation, there was a decrease
      in CD45/CD11b- and CD45/B220-positive (+) cells. This decrease was accompanied by
      a decrease in mRNA and protein expression of pro-inflammatory cytokines and a
      decrease in nuclear factor kappaB (NF-kappaB) DNA binding activity in the brain
      of stroke animals treated with HUCBCs. In addition to modulating the inflammatory
      response, we demonstrate that the cord blood cells increase neuronal survival
      through non-immune mechanisms. Once thought of as "cell replacement therapy," we
      now propose that cord blood treatment in stroke reduces inflammation and provides
      neuroprotection. Both of these components are necessary for effective therapy.

PMID- 16305345
TI  - Hypomethylation of urokinase (uPA) promoter in breast and prostate cancer:
      prognostic and therapeutic implications.
AB  - Methylation of CpG islands of tumor suppressor genes, growth factors, and hormone
      receptors among other genes causes epigenetic changes in chromatin structure
      without altering DNA sequence to regulate transcription of these genes. This
      epigenetic regulation of gene expression plays an important role in the process
      of tumor invasion, growth and metastasis in malignancies. In hormone dependent
      malignancies such as breast and prostate cancer, sex steroids play an important
      role in the process of tumor initiation and progression. These malignancies are
      often initiated as a less aggressive hormone-responsive type that gradually
      progresses to become highly invasive and hormone-insensitive. At the early
      stages, cells lose a functional hormone receptor due to mutations, blockage of
      signaling pathway or hormone receptor gene silencing. This transition of cancer
      cells causes them to become refractory to the standard hormone therapies. In
      later stages, important factors like growth factors, cytokines and proteases
      promote tumor growth, invasion and metastases. The most commonly implicated
      protease in these processes is urokinase type plasminogen activator (uPA), which
      is known to be expressed in a number of malignancies including breast and
      prostate cancer and is directly associated with the higher invasive and
      metastatic potential of malignancies. In this chapter, we will review DNA
      methylation as the underlying molecular mechanism regulating uPA gene expression
      and its potential diagnostic, prognostic and therapeutic implication.

PMID- 16305346
TI  - Targeting invasion induction as a therapeutic strategy for the treatment of
      cancer.
AB  - The spread of cancer cells from the primary tumor to a distant site involves many
      of the invasive processes normally required for wound healing, including
      migration through the local connective tissue, invasion of the vasculature,
      extravasation, invasion of the connective tissue at a distant site, and
      angiogenesis. Thus, the abilities of tumor cells to invade the host, and to
      induce endothelial cell invasion and neovascularization, are central to malignant
      progression. The plasminogen activator system, which plays a direct role in
      stimulating alpha5beta1 integrin fibronectin receptor-mediated invasion during
      wound healing, is also very important in tumor cell invasion and metastasis, as
      well as in angiogenesis. Therefore, the alpha5beta1 receptor and the plasminogen
      activator system may be promising targets for directed anticancer therapies.

PMID- 16305347
TI  - Cancer therapy through control of cell migration.
AB  - Cell migration plays a pivotal role in a many biological process that are
      essential for development, repair, and pathogenesis. Thus, inhibition of
      migration has the potential of limiting or suppressing the development of various
      diseases. Much of the focus on the therapeutic treatment of cancer has involved
      compounds that target cell proliferation and subsequent cell death. However,
      targeting migration is another approach that has not been pursued but holds
      promise for alternative means of therapy. One such potential therapeutic is a
      small protein that inhibits the migration of a number of cell types. This protein
      is derived from the amino terminal end of the 24 kDa form of fibroblast growth
      factor, and suppresses migration in the presence of a variety of growth factors.
      Analysis of the protein in mouse models shows that it inhibits in vivo
      angiogenesis and tumor growth at low concentrations. Thus, inhibition of
      migration is a viable alternative to more traditional methods of therapeutically
      treating tumors. Further study of the mechanism of inhibition can lead to the
      development of novel drugs targeting a distinctive cell process.

PMID- 16305348
TI  - Inhibition of angiogenesis by cleaved high molecular weight kininogen (HKa) and
      HKa domain 5.
AB  - High molecular weight kininogen (HK) is an abundant, multi-domain plasma protein
      that circulates in plasma primarily in its single chain form. Proteolytic
      cleavage of HK by plasma kallikrein releases the vasoactive nanopeptide
      bradykinin (BK), and converts HK into two-chain HK (HKa). BK appears to have pro
      angiogenic activity, most likely mediated through binding to B1 and B2 receptors
      on endothelial cells. Conversely, HKa and its domain 5, but not (single chain)
      HK, have potent anti-angiogenic activity comparable to other endogenous
      angiogenesis inhibitors. The mechanism by which HKa exerts its anti-angiogenic
      activity remains controversial, but appears to involve binding to cell surface
      tropomyosin and induction of apoptosis of proliferating endothelial cells. A role
      for tropomyosin in mediating the anti-angiogenic signals of other anti-angiogenic
      proteins such as endostatin and histidine-proline-rich glycoprotein (HPRG) has
      also been reported. Here we review the physiological importance of high molecular
      weight kininogen in angiogenesis, with emphasis on the mechanism(s) by which this
      activity is mediated.

PMID- 16305349
TI  - Anti-angiogenic and anti-tumor properties of proteasome inhibitors.
AB  - Tumor growth and metastasis depend on the formation of blood vessels,
      angiogenesis, to supply the developing mass with nutrients, oxygen, and waste
      removal. The proteasome, a massive multisubunit catabolic body, exerts a
      regulatory influence on angiogenesis. Inhibition of the proteasome activity has
      been found to inhibit angiogenesis and induce apoptosis in human cancer cells
      with limited toxicity to normal cells. Therefore, the dual action of angiogenesis
      inhibition and cell death induction makes proteasome inhibition an attractive
      modality for chemotherapy. A variety of proteasome inhibitors have been studied
      including: antibiotics such as lactacystin, the green tea polyphenols, and the
      boronic acid Velcade (MLN-341). Most recently, certain classes of copper
      compounds have been found to act as potent proteasome inhibitors. The potential
      of particular organic compounds, such as 8-hydroxyquinoline, to spontaneously
      bind with tumor cellular copper and form proteasome inhibitors provides a new
      modality of anti-proteasome and anti-angiogenesis chemotherapy. This review
      examines angiogenesis, the proteasome, representative proteasome inhibitors, and
      the emerging role of copper. The formation of new blood vessels, or angiogenesis,
      is an important and necessary function in both embryonic development and wound
      repair. Therefore, the ability to regenerate or form new vessels for blood flow
      is essential. The control of angiogenic pathways is tightly regulated in normal
      differentiated adult cells, which generally do not stimulate blood vessel growth
      unless injury occurs. However, cancerous tissues stimulate angiogenesis that in
      turn leads to increased tumor formation and possible metastases. Many of the
      factors involved in angiogenesis are regulated by the proteasome, which recently
      has become a focus in anti-cancer therapies due to its involvement in cell cycle
      and apoptosis control. Here we discuss angiogenesis and its relation to the
      proteasome. Additionally, current modalities of anti-angiogenic treatment, mainly
      proteasome inhibitory strategies, are reviewed. Furthermore, proteasome
      inhibitors, both natural and synthetic, and their anti-angiogenic effects as well
      as future approaches to anti-angiogenic chemotherapies are also discussed.

PMID- 16305350
TI  - Control of copper status for cancer therapy.
AB  - Copper is a trace element which is tightly regulated in mammals and lower
      animals. Disruptions of copper homeostasis in humans are rare and they cause
      serious disorders such as Wilson's disease and Menke's disease. Copper plays an
      important role in promoting physiological and malignant angiogenesis. Formation
      of new blood vessels by a tumor enables tumor growth, invasion, and metastasis
      are copper requiring processes. The copper chelator tetrathiomolybdate (TM),
      which quickly and effectively depletes copper stores, is under investigation as
      an anti-angiogenic agent. Promising results from in vitro experiments, in pre
      clinical animal models, and in a phase I clinical trial have led to several phase
      II trials of TM in patients with advanced cancers.

PMID- 16305351
TI  - Cellular and molecular surrogate markers to monitor targeted and non-targeted
      antiangiogenic drug activity and determine optimal biologic dose.
AB  - Perhaps the most significant recent advance in oncology therapeutics has been the
      approval of various "molecularly targeted" anti-cancer drugs. Currently, there
      are a large number of similar drugs in early or late stage development, including
      antiangiogenic agents. Clinical development of such drugs suffers from several
      handicaps including determining whether a patient's cancer expresses the target
      and is functionally contributing to cancer growth, monitoring biologic activity,
      and determining optimal biologic dose. The last problem is related to the low
      frequency of objective tumor responses (tumor shrinkage) caused by such drugs, or
      the lack of dose limiting toxicities necessary to define a maximum tolerated dose
      (MTD), or expression of optimal therapeutic activity at doses below the MTD, when
      one can be defined. These problems necessitate the development of alternative
      pharmacodynamic surrogate markers. Here we summarize several such promising
      markers for monitoring targeted antiangiogenic activity, and establishing optimal
      therapeutic/biologic dosing. The first is molecular--plasma VEGF--levels of which
      are rapidly and significantly increased in a dose dependent manner after
      injection of normal or tumor bearing mice with anti-VEGFR-2 antibodies. The
      second is a cellular marker, and more generic in nature--circulating VEGF
      receptor-2 positive cells found in peripheral blood, some of which may be
      circulating endothelial progenitor cells. Levels of such cells are suppressed in
      a dose dependent manner which correlate with previously determined optimal
      biologic/therapeutic anti-tumor activity of various antiangiogenic drugs or
      treatments. Finally, another promising marker we discuss is soluble VEGFR-2.

PMID- 16305353
TI  - Prospects for combinatorial chemistry in the agrosciences.
AB  - The recent progress and future prospects for the successful application of
      combinatorial chemistry and high throughput screening within the agrochemical
      lead discovery process are outlined and discussed. Solid and solution phase
      library synthesis technologies are reviewed and compared, and the role and
      importance of bioavailability, diversity and virtual screening in rational
      library design are detailed.

PMID- 16305354
TI  - Applications of combinatorial chemistry in the agrosciences.
AB  - During the past ten years combinatorial chemistry developed from a powerful
      synthetic methodology, providing large libraries of usually simple new chemical
      entities, to a comprehensive strategy presently covering a multitude of
      technologies across the whole workflow from hit generation to lead optimization.
      Thus combinatorial chemistry had a major impact not only on the pharmaceutical
      research but also with some delay on the agrochemical research. The agrochemical
      discovery environment is different from that of the pharmaceutical research in
      that it relies mainly on whole organism screenings. This review summarizes some
      recent applications of combinatorial chemistry in the agrosciences, covering all
      the three major fields of research: fungicides, herbicides, and insecticides. The
      article focuses on libraries with published biological activities and thus
      highlights some characteristic features of successful agrochemical libraries,
      which may be fundamentally different from pharmaceutical libraries.

PMID- 16305355
TI  - Targeting chemical inputs and optimising HTS for agrochemical discovery.
AB  - In vivo high throughput screening (HTS) has been adopted by most of the larger
      crop protection companies as an important tool for the discovery of new
      agrochemicals. There has been a paradigm shift in capabilities from screening a
      few thousand compounds a year to several hundred thousand and the quantity of
      screening sample required has fallen dramatically. The unifying goal now bringing
      together screens and inputs is the need to maximise the flow of useful
      information from HTS and thereby minimise the time taken to discover robust leads
      and new products. This review examines the positive changes that have occurred
      towards targeted design and selection of chemical inputs for agrochemical
      discovery over the last ten years and corresponding developments in HTS assays,
      data analysis and the logistics of compound storage and dispensing.

PMID- 16305356
TI  - High throughput screening in agrochemical research.
AB  - The demand for new herbicides, insecticides and fungicides led to a steady
      increase in the number of compounds being tested to find novel market products.
      To keep pace with the rising workload, high throughput screening (HTS)
      technologies have been introduced. In agrochemical research miniaturised in vivo
      tests on whole real target organisms are now possible and are an integral part of
      the screening cascade. A complementary target based in vitro HTS has also been
      established in agrochemical research. Target based HTS allows a directed approach
      towards untouched market shares by novel modes of action. Selection of the best
      suited targets is the most crucial issue in this approach. Genomic methods
      thereby deliver many essential genes as candidate targets. Consideration of
      further criteria such as druggability notably narrows down the number of
      promising targets. Though target to hit to lead progression still is as in
      pharmaceutical research a complex and therefore risky process, the implementation
      of novel bioscience technologies has entailed the transition to an integrated
      innovative agrochemical research perspective.

PMID- 16305357
TI  - Recent advances in microwave-assisted combinatorial synthesis and library
      generation.
AB  - Progress and developments made in microwave-assisted combinatorial synthesis and
      library production since 2002 are reviewed. The use of microwave technology in
      both solution and solid phase synthesis is discussed with special reference to
      agrochemical applications where appropriate.

PMID- 16305358
TI  - Synthesis and agrochemical screening of a library of natural product-like
      bicyclo[2,2,2]octenones.
AB  - A general route to a series of differentially substituted bicyclo[2,2,2]octenones
      has been developed, making use of the in situ intramolecular Diels Alder reaction
      of masked ortho-benzoquinones. This approach was used to synthesize a series of
      thirteen key acid-containing templates from which a solution phase discovery
      library of 1126 diverse amides was then constructed. The rigid polycyclic nature
      of the templates and the prevalence of oxygenated functionality confer natural
      product-like qualities and three-dimensional diversity. The library was screened
      in HTS in vivo against a number of weed, insect and fungal model organisms
      leading to the discovery of a novel series of herbicidally active compounds. The
      development, production and biological activity of the library are described.

PMID- 16305359
TI  - Parallel, solution phase synthesis of dihydropyridine miticides via a versatile
      multicomponent reaction.
AB  - A novel class of highly active dihydropyridine miticides was prepared using a
      multicomponent reaction process. The initial lead was rapidly optimized using
      solution phase parallel synthesis techniques and a positional scanning approach.
      Detailed structure-activity relationships were developed for the amino and
      carbonyl components of the molecule and used to select the best candidates for
      broad field testing. The chemistry, biology and toxicology of these compounds
      will be presented along with numerous structural variants of the reaction
      products.

PMID- 16305360
TI  - The design and synthesis of a herbicide targeted library of N-[1-(1,3-benzoxazol
      2-yl)alkyl]-6-alkyl-1,3,5-triazine-2,4-diamines.
AB  - Amino acids were immobilised by attaching them via a carbamate linker to Wang
      resin. These intermediates were converted to 1-(1,3-benzoxazol-2-yl)alkanamines
      over three steps, followed by coupling with 4-alkyl-6-chloro-1,3,5-triazine-2
      amines to furnish the desired N-[1-(1,3-benzoxazol-2-yl)alkyl]-6-alkyl-1,3,5
      triazine-2,4-diamines. Physico-chemical property profiles were used to support
      design and development of a combinatorial library. The synthetic methodology
      described herein was validated with the production of a herbicide targeted
      library of 300 members.

PMID- 16305361
TI  - Automated Synthesis and Purification at Bayer CropScience Chemistry Frankfurt.
AB  - The Automated Synthesis and Purification team at Bayer CropScience in Frankfurt
      provides services and support in the areas of synthesis and post synthesis
      activities for chemists. This article describes our workflow and the special
      robotic systems used. We produce small to medium sized compound libraries using
      liquid phase techniques. An example of a compound library taken from the
      herbicide area is given.

PMID- 16305362
TI  - Solid supported synthesis of phosphinates via palladium (0) catalysed coupling
      reactions.
AB  - In order to gain a broad access to phosphinic acid derivatives, a palladium
      catalysed coupling reaction of aryl iodides with hypophosphorous acid derivatives
      has been developed on the solid phase. The resulting arylphosphorous acids (or
      esters) were derivatised using addition reactions with aldehydes, imines and
      isocyanates, to give phosphinic acids (or esters) with alpha-hydroxy, alpha-amino
      or aminoacyl groups attached to the aryl phosphorus moiety. This approach
      provided a broad chemical entry into a class of polar phosphinates compounds
      which were rather difficult to handle using normal solution phase synthesis. The
      synthetic potential of this solid phase based methodology was demonstrated by the
      synthesis of targeted libraries against the enzyme dihydrodipicolinate synthase
      (DHDPS).

PMID- 16305363
TI  - Communication: polymer-assisted solution-phase synthesis of 4,5-dihydro-1,4
      benzoxazepin-3(2H)-ones.
AB  - The polymer assisted solution phase (PASP) synthesis of 4,5-dihydro-1,4
      benzoxazepin-3(2H)-ones is described. Using salicylic aldehydes, alpha-bromo
      acetic acid esters, and primary amines as broadly variable building blocks, the
      target molecules were obtained in a straightforward manner. The use of polymer
      bound reagents and scavengers greatly simplified workup, and avoided the use of
      protecting groups. A small library was prepared, showing the feasibility of the
      synthetic concept for the generation of larger sets of screening compounds.

PMID- 16305364
TI  - The design, synthesis and screening of a muscarinic acetylcholine receptor
      targeted compound library.
AB  - Potent new agonists of the insect muscarinic acetylcholine receptor (mAChR) have
      been discovered by synthesizing and screening a library of 225 oxime ether
      amines. Library evaluation was facilitated by the development of a high
      throughput test enabling the rapid determination of muscarinic agonist activity.
      The most interesting compounds were the thiadiazole 17 and the isoxazole 24 which
      were potent muscarinic agonists (EC50 13 and 21 nM, respectively) and showed lead
      levels of insecticidal activity.

PMID- 16305365
TI  - ATP-containing immunoliposomes specific for cardiac myosin.
AB  - The application of ATP-loaded liposomes has been shown effective against ischemic
      damage in several tissues. In this study, we have prepared ATP-containing
      liposomes capable of specific recognition of component (myosin) specific for
      ischemic myocardium. ATP-containing immunoliposomes specific towards cardiac
      myosin were obtained by the attachment of the monoclonal anti-cardiac myosin 2G4
      antibody to the surface of ATP-containing PEGylated liposomes prepared by the
      freezing-thawing method. Since intracellular myosin is exposed only in the areas
      containing ischemically compromised cells with damaged plasmic membranes, such
      liposomes are expected to target these areas both in vitro and in vivo. The
      attachment of the antibody did not provoke their ATP release from the liposomes
      and only minimally influenced liposome size and size distribution. Liposome
      attached anti-myosin 2G4 antibody preserved its specific activity; and anti
      myosin antibody-bearing, ATP-loaded liposomes bound efficiently to the monolayer
      of myosin in ELISA. The preparation of myosin-specific ATP-loaded immunoliposomes
      represented an important step in the development of targeted delivery systems
      capable of providing energy support to ischemic myocardium in vivo.

PMID- 16305366
TI  - Biphasic lipid vesicles (Biphasix) enhance the adjuvanticity of CpG
      oligonucleotides following systemic and mucosal administration.
AB  - CpG oligonucleotides (ODNs) are potent mucosal and systemic adjuvants. For
      practical applications however, improvements in delivery need to be developed. A
      mouse model was used to determine if the biological activity of CpG ODNs could be
      enhanced using a novel delivery system of biphasic lipid vesicles (Biphasix
      Vaccine-Targeting Adjuvant; VTA). Immunization studies were performed to evaluate
      the potential of VTA formulations to enhance the immunoadjuvant activity of CpG
      ODNs following systemic or mucosal administration with gD. Immune responses
      following immunization were assessed by protection from HSV-1 viral challenge and
      characterization of serum gD-specific antibody responses using ELISA. VTA
      formulations in combination with CpG and glycoprotein D (gD) were able to
      increase gD-specific IgG in serum compared to gD alone, and protect from a lethal
      HSV-1 challenge following subcutaneous immunization. Following mucosal
      immunization, VTA formulations in combination with CpG and antigen enhanced
      mucosal IgA responses compared to CpG and antigen administered in PBS.

PMID- 16305367
TI  - Formulation and characterisation of tetracycline-containing bioadhesive polymer
      networks designed for the treatment of periodontal disease.
AB  - This study described the drug release, rheological (dynamic and flow) and
      textural/mechanical properties of a series of formulations composed of 15% w/w
      polymethylvinylether-co-maleic anhydride (PMVE-MA), 0-9% w/w polyvinylpyrrolidone
      (PVP) and containing 1-5% w/w tetracycline hydrochloride, designed for the
      treatment of periodontal disease. All formulations exhibited pseudoplastic flow
      with minimal thixotropy. Increasing the concentration of PVP sequentially
      increased the zero-rate viscosity (derived from the Cross model) and the hardness
      and compressibility of the formulations (derived from texture profile analysis).
      These affects may be accredited to increased polymer entanglement and, in light
      of the observed synergy between the two polymers with respect to their textural
      and rheological properties, interaction between PVP and PMVE-MA. Increasing the
      concentration of PVP increased the storage and loss moduli yet decreased the loss
      tangent of all formulations, indicative of increased elastic behaviour. Synergy
      between the two polymers with respect to their viscoelastic properties was
      observed. Increased adhesiveness, associated with increased concentrations of PVP
      was ascribed to the increasing bioadhesion and tack of the formulations. The
      effect of increasing drug concentration on the rheological and textural
      properties was dependent on PVP concentration. At lower concentrations (0, 3%
      w/w) no effect was observed whereas, in the presence of 9% w/w PVP, increasing
      drug concentration increased formulation elasticity, zero rate viscosity,
      hardness and compressibility. These observations were ascribed to the greater
      mass of suspended drug in formulations containing the highest concentration of
      PVP. Drug release from formulations containing 6 and 9% PVP (and 5% w/w drug) was
      prolonged and swelling/diffusion controlled. Based on the drug release,
      rheological and textural properties, it is suggested that the formulation
      containing 15% w/w PMVE-MA, 6% w/w PVP and tetracycline hydrochloride (5% w/w)
      may be useful for the treatment of periodontal disease.

PMID- 16305368
TI  - The role of ABC transporters in drug resistance, metabolism and toxicity.
AB  - ATP Binding Cassette (ABC) transporters form a special family of membrane
      proteins, characterized by homologous ATP-binding, and large, multispanning
      transmembrane domains. Several members of this family are primary active
      transporters, which significantly modulate the absorption, metabolism, cellular
      effectivity and toxicity of pharmacological agents. This review provides a
      general overview of the human ABC transporters, their expression, localization
      and basic mechanism of action. Then we shortly deal with the human ABC
      transporters as targets of therapeutic interventions in medicine, including
      cancer drug resistance, lipid and other metabolic disorders, and even gene
      therapy applications. We place a special emphasis on the three major groups of
      ABC transporters involved in cancer multidrug resistance (MDR). These are the
      classical P-glycoprotein (MDR1, ABCB1), the multidrug resistance associated
      proteins (MRPs, in the ABCC subfamily), and the ABCG2 protein, an ABC half
      transporter. All these proteins catalyze an ATP-dependent active transport of
      chemically unrelated compounds, including anticancer drugs. MDR1 (P-glycoprotein)
      and ABCG2 preferentially extrude large hydrophobic, positively charged molecules,
      while the members of the MRP family can extrude both hydrophobic uncharged
      molecules and water-soluble anionic compounds. Based on the physiological
      expression and role of these transporters, we provide examples for their role in
      Absorption-Distribution-Metabolism-Excretion (ADME) and toxicology, and describe
      several basic assays which can be applied for screening drug interactions with
      ABC transporters in the course of drug research and development.

PMID- 16305369
TI  - An MDR-EGFP gene fusion allows for direct cellular localization, function and
      stability assessment of P-glycoprotein.
AB  - In cancer and AIDS, overexpression of the MDR1 gene has important implications in
      the design of chemotherapy protocols because of the ability of its product, the
      ATP-dependent drug efflux pump P-glycoprotein (Pgp), to confer selective
      advantage to tumor and HIV-infected cells in the form of multidrug resistance. To
      study Pgp expression and physiology, we designed a translational fusion between
      the MDR1 and enhanced green fluorescent protein (EGFP) genes. The chimeric
      protein, Pgp-EGFP, was concentrated mainly in the plasma membrane and in the
      Golgi when expressed in drug-sensitive KB-3-1 cells. Doxorubicin, daunorubicin
      and rhodamine-123 efflux assays confirmed function of the chimeric pump. Also, at
      the single-cell level, an inverse relationship between Pgp-EGFP expression and
      nuclear doxorubicin accumulation was demonstrated. Polarized Pgp expression on
      the apical cell surface was confirmed by transfection of the MDR-EGFP fusion gene
      into MDCK cells. However, after colchicine selection, Pgp-EGFP was also
      detectable in the lateral domain of the transfected MDCK monolayers. These
      results indicate that drug selection affects not only expression, but cellular
      localization of Pgp. Furthermore, using a tet-based inducible expression system
      for Pgp-EGFP, we confirmed the stable nature of Pgp (t(1/2 total Pgp-EGFP) = 2.2
      days), but revealed that surface-Pgp acquires extra stability as an active pump
      (t(1/2 surface Pgp-EGFP) = 3.7 days).

PMID- 16305370
TI  - Pain control via opioid analgesic-local anesthetic loaded IPNs.
AB  - Relief of chronic pain is an important clinical problem requiring special care
      and approaches. The present study was designed for the construction of a
      controlled release system for local application of analgesics (hydromorphone
      (HM), morphine (M), and codeine (C)) and a local anesthetic, bupivacaine (BP). An
      interpenetrating network (IPN) drug release system was prepared by using a
      biocompatible, biodegradable copolyester, poly(3-hydroxybutyrate-co-3
      hydroxyvalerate) (PHBV) and another biocompatible but synthetic, nondegradable
      polymer, poly (2- hydroxyethyl methacrylate), (PHEMA). In situ release kinetics
      of the IPN system was first order for BP but could not be fitted to any known
      equation for the other drugs. Complete release from the IPNs occurred within a
      considerably short time (24 h for 80 % of the drugs) most probably due to the
      significant hydrophilicity of PHEMA. In order to slow down the release rate these
      IPNs were coated with PHBV. Release from these coated IPNs (cIPN) resulted in
      rates that could be described by Higuchi's equations. In vivo measurement of
      antinociceptive efficacy was carried out in rats with tail flick and paw
      withdrawal tests after inducing chronic pain created by sciatic nerve ligation at
      the right side. Control groups received placebo implants. In vivo studies showed
      potent, prolonged (2-3 days) antinociception at the site of injury (right paw)
      for strong opioids (HM and M) and about 2 days for the weak opioid (C) and local
      anesthetic (BP). In all cases the release rate was found to be as important as
      the antinociceptive potency. The weakest opioid analgesic of those evaluated (C)
      had a higher first day antinociception than its stronger counterpart M, probably
      due to its higher initial concentration that was expected from its faster release
      rate in the in situ experiments.

PMID- 16305371
TI  - Development of topically effective formulations of acetazolamide using HP-beta-CD
      polymer co-complexes.
AB  - The myriad of side effects induced by acetazolamide (oral use), the introduction
      of newer topical carbonic anhydrase inhibitors (CAI's) and the advent of other
      antiglaucoma medications has led to a decreased interest in acetazolamide. The
      use of cyclodextrins to improve the solubility and bioavailability of poorly
      soluble drugs has however, rekindled an interest in acetazolamide (ACZ), because
      its poor solubility is one of the major factor responsible for its failure to
      show topical effectiveness. Since water soluble polymers have been reported to
      improve the complexing capabilities of beta-cyclodextrins, in the present study
      water soluble polymers like polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP),
      hydroxypropymethylcellulose (HPMC) and the mucoadhesive polymer Carbopol 934P
      were incorporated into aqueous 10% w/v 2HP-beta-CD solution to improve the
      solubility of ACZ. The effect of these polymers on the corneal transport of 5
      mg/ml (0.5% w/v) solution of ACZ in aqueous 10% 2HP-beta-CD was evaluated. The
      inclusion of these polymers significantly increased the solubility of ACZ from
      3.43 mg/ml in aqueous 10% 2HP-beta-CD to 5.1 mg/ml (48.6%) in 0.05% PVP; 6.80
      mg/ml (98.3%) in 0.05% PVA; and 6.74 mg/ml (96.5%) in 0.2% Carbopol 934P. From
      amongst the various polymers assessed in the study, PVA was deemed the best,
      based on the premise of better apparent permeability coefficient (P(app)) upon in
      vitro corneal permeation studies. Inspite of a large enhancement in solubility
      produced by Carbopol 934P, surprisingly, it could not efficiently increase the
      Papp.

PMID- 16305372
TI  - Challenges in current drug delivery from the potential application of
      pharmacogenomics and personalized medicine in clinical practice.
AB  - The recent technological achievements in biotechnology and recombinant DNA
      technology have provided multiple new methods, molecular targets, and DNA-based
      diagnostics to pharmaceutical research that can be utilized in assays for
      screening and developing potential biotechnology-based drugs, as well as in
      biomedicine, health and pharmaceutical care. Furthermore, such advances opened up
      new opportunities by applying genetic information data in pharmacotherapy and
      drug delivery, thus ensuring better drug efficacy and safety in clinical
      practice. Now the concepts of personalized medicine and pharmacogenomics are
      likely improving the area of pharmacodynamics and pharmacokinetics, since they
      favor differentiation of the conventional clinical diagnosis and drug selection
      into separate molecular subtypes of individuals belonging within a group of
      patients suffering from the same disease. Genetic polymorphisms have already been
      detected and analyzed in genes encoding drug-metabolizing enzymes, transporters
      as well as targets (e.g. receptors). The potential of applying genotyping and
      haplotyping analysis in future pharmaceutical care could eventually lead to
      pharmacotyping, i.e. individualized drug delivery profiling based on genetic
      bioinformatic data in routine patient care. However, the steps towards this
      direction of drug delivery in clinical practice still have a long way to go to be
      fully achieved; until then, the critical evaluation of all available clinical
      data including pharmacodynamic, pharmacokinetic and genomic must be assessed for
      ensuring drug efficacy and safety. In this way, there has been great progress in
      elucidating genetic determinants contributing to the observed interindividual
      differences in drug disposition and effects, thus implementing current drug
      delivery with molecular genetics and diagnostics.

PMID- 16305373
TI  - Physical enhancement of transdermal drug application: is delivery technology
      keeping up with pharmaceutical development?
AB  - Advances in molecular biology have given us a wide range of protein and peptide
      based drugs that are unsuitable for oral delivery because of their high degree of
      first-pass metabolism. Though parenteral delivery is the obvious answer, for the
      successful development of commercial chronic and self-administration usage
      formulations it is not the ideal choice. Transdermal delivery is emerging as the
      biggest application target for these agents, however, the skin is extremely
      efficient at keeping out such large molecular weight compounds and therapeutic
      levels are never going to be realistically achieved by passive absorption.
      Physical enhancement mechanisms including: iontophoresis, electroporation,
      ultrasound, photomechanical waves, microneedles and jet-propelled particles are
      emerging as solutions to this topical delivery dilemma. Adding proteins and
      peptides to the list of other large molecular weight drugs with insufficient
      passive transdermal fluxes to be therapeutically useful, we have a collection of
      pharmacological agents waiting for efficient delivery methods to be introduced.
      This article reviews the current state of physical transdermal delivery
      technology, assesses the pros and cons of each technique and summarises the
      evidence-base of their drug delivery capabilities.

PMID- 16305374
TI  - Studies on the transdermal delivery of nimodipine from a menthol-based TTS in
      human volunteers.
AB  - The purpose of the present study was to design a membrane-moderated transdermal
      therapeutic system (TTS) of nimodipine using 2%w/w hydroxypropyl methylcellulose
      (HPMC) gel as a reservoir system containing menthol as penetration enhancer and
      60%v/v ethanol-water as solvent system. The flux of nimodipine was markedly
      increased from 35.51 microg/cm2/h to 167.53+/-3.69 microg/cm2/h with the addition
      of 8%w/w menthol to HPMC drug reservoir. There was an increase in the flux of
      nimodipine through ethylene vinyl acetate (EVA) copolymer membrane with an
      increase in vinyl acetate content (9 to 28%w/w) of the copolymer. The
      permeability flux of nimodipine from the chosen EVA 2825 (with 28%w/w vinyl
      acetate content) was 152.05+/-2.68 microg/cm2/h, and this flux decreased to
      132.69+/-1.45 microg/cm2/h on application of a water-based acrylic adhesive
      (TACKWHITE A 4MED) coat. However, the transdermal flux of nimodipine across EVA
      2825 membrane coated with TACKWHITE A 4MED/ rat skin composite was found to be
      116.05+/-2.39 microg/cm2/h, which is about 1.4 times greater than the required
      flux. Thus a new transdermal therapeutic system for nimodipine was designed using
      EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE 4A MED, and
      2%w/w HPMC gel as reservoir containing 8%w/w of menthol as a penetration
      enhancer. The in vivo evaluation of nimodipine TTS patch was carried out to find
      the ability of the fabricated menthol-based TTS patch in providing the
      predetermined plasma concentration of the drug in human volunteers. The results
      showed that the menthol-based TTS patch of nimodipine provided steady plasma
      concentration of the drug with minimal fluctuations with improved bioavailability
      in comparison with the immediate release tablet dosage form.

PMID- 16305375
TI  - Alkaline hydrolysis as a tool to determine the association form of indomethacin
      in nanocapsules prepared with poly(eta-caprolactone).
AB  - To determine the association form of indomethacin in nanocapsules prepared with
      poly(eta-caprolactone) as polymer and a triglyceride as oil, two methods were
      studied. The indomethacin ethyl ester was prepared as control, which showed a
      higher affinity for the oil than the indomethacin. Two differently loaded
      nanocapsule formulations were prepared. For both formulations, a burst effect was
      detected using ethanol as release medium. Light scattering (PCS) and NMR analyses
      suggested the ethanol diffuses through the nanocapsule polymeric wall promoting
      the total release of indomethacin and its ester. The results showed the inability
      of this approach to determine the association form of indomethacin. On the other
      hand, the alkaline hydrolysis of indomethacin and its ester, followed by their
      disappearance (HPLC), were evaluated. The nanocapsule suspensions containing
      indomethacin or its ester were treated with 50 mM NaOH. The total disappearance
      of indomethacin associated with nanocapsules was determined after 2 min, whereas
      the ester associated with colloids was consumed during 24 h. The constant
      particle sizes (264 and 259 nm) during the hydrolysis reactions showed that
      neither the nanocapsules were dissolved nor the polymer sorbed water during the
      contact with NaOH aqueous solution. The ester rate hydrolysis was determined by
      its diffusion from the nanocapsules to the interface particle/water. Finally, the
      indomethacin association model considers the burst release of drug after the
      addition of NaOH by the formation of its carboxylate, followed by its hydrolysis
      in aqueous solution promoted by the excess of NaOH. The adsorption was the
      mechanism of indomethacin association with nanocapsules.

PMID- 16305376
TI  - Influence of the monomers type on the morphology of polyamide microcapsules.
AB  - Various polyamide microcapsules were prepared via an inverse emulsion system
      (water in oil) by interfacial polycondensation of terephthaloyl dichloride with
      the aliphatic diamines ethylene diamine (EDA) and 1,6-hexane diamine (HMDA), and
      the aromatic diamine 1,4-phenylene diamine (PDA). Three types of polyamide
      microcapsules were thus obtained and labeled: CAPS EDA, CAPS HMDA, and CAPS PDA,
      respectively. The influence that the various substitutions had on particle size
      distribution, membrane microstructure, porosity and specific surface area and
      water content of the polyamide microcapsule was investigated. The roughness,
      porosity and porous volume of the polyamide membrane increased in the order: CAPS
      EDA < CAPS HMDA < CAPS PDA. Sodium chloride permeation experiments were performed
      to obtain an insight into the impact of structural changes on the permeability of
      the microcapsules to ionic species. The NaCl diffusion and permeability
      coefficients through the microcapsules were found to be in the order of 10(-8)
      cm2/s and 10(-5) cm/s, respectively.

PMID- 16305377
TI  - A new N-acetylgalactosamine containing peptide as a targeting vehicle for
      mammalian hepatocytes via asialoglycoprotein receptor endocytosis.
AB  - Galactoside-containing cluster ligands have high affinity for asialoglycoprotein
      receptors (ASGP-r), which are found in abundance in mammalian parenchymal liver
      cells. These ligands may be conjugated with a therapeutic drug to improve the
      efficiency of delivery to diseased liver cells. This report describes a new
      synthetic route towards clustering glycopeptides containing N-acetyl-D
      galactosamine (GalNAc). The building block Fmoc-alpha-(ah-Ac3GalNAc)-L-glutamate
      allowed access to the target compound YEEE(alpha-ah-GalNAc)(3), a structural
      mimic of YEE(ah-GalNAc)(3), via solid phase peptide synthesis (SPPS). Fatty acid,
      poly-lysine, fluorescein and biotin conjugates further demonstrate the facility
      of the described method. Using fluorescein labeling and 131I labeling, in vitro
      and in vivo assays confirmed that YEEE(alpha-ah-GalNAc)(3) possesses both
      specificity and affinity to the liver, similar to the agent YEE(ah-GalNAc)(3),
      which targets liver lesions. The synthesis described in this report represents a
      considerable improvement in synthesizing a ligand for ASGP-r by simplifying both
      the preparation of the starting material and the procedure for conjugating the
      galactosidase cluster to drugs.

PMID- 16305378
TI  - Human vaginal mucosa as a model of buccal mucosa for in vitro permeability
      studies: an overview.
AB  - The buccal cavity is attractive for noninvasive, controlled transmucosal delivery
      of both local and systemic therapeutically active compounds. Administering drugs
      via this route is advantageous due to the rich vasculature of the oral mucosa,
      and the absence of gastrointestinal and "first-pass" hepatic degradation.
      Moreover, the barrier properties of the oral mucosa against noxious substances
      and its role in disease require further investigation. However, the scarcity of
      sizeable specimens of human oral mucosa for in vitro experimental studies has
      hampered research on this tissue. For this reason we developed a model in which
      human vaginal mucosa is used as a substitute for buccal mucosa. In this article
      the quality and predictive value of the human vaginal/buccal in vitro model with
      respect to a number of drugs and other chemical compounds differing widely in
      molecular size and lipophilicity, including water, arecoline, arecaidine,
      benzo[a]pyrene, 17beta-estradiol, sumatriptan, vasopressin and dextrans, are
      reviewed. In addition some applications of the model for investigating the effect
      of areca nut extract on epithelial barrier properties, temperature effects on
      water and 17beta-estradiol flux rates, and cyclosporin diffusion through mucosal
      membranes are described. The permeability characteristics of vaginal mucosa, as a
      model of buccal mucosa, are compared with those of other human tissue, including
      mucosae from the small intestine and colon.

PMID- 16305379
TI  - Passive and iontophoretic controlled delivery of salmon calcitonin through
      artificial membranes.
AB  - The development of a transdermal delivery system for drug molecules of high
      molecular weight (peptides or proteins) is nowadays a great scientific and
      commercial challenge. For these molecules, the passive transport through the skin
      is generally very low and should be enhanced by the application of the electrical
      current (a method called iontophoresis). A very important component of a
      transdermal iontophoretic system is the artificial membrane, which acts as the
      interface between the drug reservoir and the skin. The optimum membrane should
      (i) provide an effective drug delivery; (ii) have low electrical resistance and
      (ii) have low drug adsorption. In this work, the selection of membrane(s) for a
      transdermal iontophoretic salmon calcitonin (sCT, MW approximately 3500) system
      is performed. The passive and iontophoretic transport of sCT through porous
      artificial membranes, the sCT adsorption to them and the electrical resistance of
      all porous membranes in iontophoretic experiments is studied. The sCT transport
      through the membranes is compared with that through human skin, and based on the
      above three criteria the optimum membranes are selected for the sCT transdermal
      system.

PMID- 16305380
TI  - Phospholipid vesicles as carriers in aquaculture: preparation and stability study
      of thiamine hydrochloride-loaded liposomes.
AB  - The aim of this work is to study liposomes as carriers of nutrients and
      therapeutic agents in aquaculture with Venerupis decussatus and Venerupis
      pullastra larvae. Multilamellar (MLVs) and large unilamellar (LUVs) vesicles were
      prepared from a commercial mixture of soy phosphatidylcholine, rich in
      unsaturated and polyunsaturated fatty acids, cholesterol, and hydrated with a
      solution of vitamin B1 both in distilled and sea water. Carboxyfluorescein-loaded
      liposomes were also prepared in order to test the uptake of vesicles by larvae.
      The stability of formulations was checked by monitoring the size of vesicles and
      their drug leakage. In order to limit the vitamin loss, liposome freeze-drying
      was studied. Dried formulations were also prepared by using different amounts of
      trehalose as cryoprotectant. We found that freeze-dried vesicles, rehydrated
      after two weeks, had a vitamin retention (R%) equal to 95%, while their diameter
      significantly increased. By contrast, liposomes freeze-dried in the presence of
      trehalose displayed a lower R%, but higher bilayer stability. Finally, when CF
      loaded vesicles were added to Venerupis decussatus and Venerupis pullastra larvae
      incubated in filtered sea water, a bright and diffused fluorescence was present
      in most of the larvae, a fact which can be regarded as evidence of liposome
      uptake by Venerupis larvae.

PMID- 16305381
TI  - A new gene delivery system based on controlled release technology.
AB  - The recent rapid development of molecular biology together with the steady
      progress of genome projects has given us some essential and revolutionary
      informations of gene to elucidate all the biological phenomena at the molecular
      level. Under these circumstances, gene transfection has become a fundamental
      technology indispensable to the basic research of medicine and biology. On the
      other hand, the technology of gene transfection is also important for gene
      therapy of several diseases. Some human gene therapies have been performed with a
      plasmid DNA alone or virus vectors but are clinically limited by the poor gene
      expression of plasmid DNA and the adverse effects of virus itself, such as
      immunogenicity and toxicity or the possible mutagenesis of cells transfected.
      Therefore, several non-viral vectors of synthetic materials have been explored to
      enhance the transfection efficiency of gene into mammalian cells both in vitro
      and in vivo. In this paper, the researches about non-viral vectors and recent
      research trials about the controlled release of plasmid DNA are briefly reviewed
      to emphasize the significance of gene delivery technology in basic biology and
      medicine as well as clinical medicine. A new system of gene release based on
      biodegradable hydrogel is introduced.

PMID- 16305382
TI  - Current developments in gene transfection agents.
AB  - DNA can be delivered into the cell nucleus either using physical means or
      specific carriers that carry the genes into the cells for gene expression).
      Various carriers for delivering genes have been investigated which can be divided
      into two main groups: viral carriers where the DNA to be delivered is inserted
      into a virus, and cationic molecular carriers that form electrostatic
      interactions with DNA). Successful gene therapy depends on the efficient delivery
      of genetic materials into the cells nucleus and its effective expression within
      these cells). Although at present the in vivo expression levels of synthetic
      molecular gene vectors are lower than for viral vectors and gene expression is
      transient, these vehicles are likely to present several advantages including
      safety, low-immunogenicity, capacity to deliver large genes and large-scale
      production at low-cost). The two leading classes of synthetic gene delivery
      systems that have been mostly investigated are cationic lipids and cationic
      polymers). This review discusses recent developments in viral vectors, physical
      means and molecular gene carriers). The last part focuses on our recent studies
      in developing a new series of biodegradable polycations for in vitro and in vivo
      gene transfection).

PMID- 16305383
TI  - Polymer based drug delivery systems for mycobacterial infections.
AB  - In the last decade, polymer based technologies have found wide biomedical
      applications. Polymers, whether synthetic (e.g. polylactide-co-glycolide or PLG)
      or natural (e.g. alginate, chitosan etc.), have the property of encapsulating a
      diverse range of molecules of biological interest and bear distinct therapeutic
      advantages such as controlled release of drugs, protection against the premature
      degradation of drugs and reduction in drug toxicity. These are important
      considerations in the long-duration treatment of chronic infectious diseases such
      as tuberculosis in which patient non-compliance is the major obstacle to
      successful chemotherapy. Antitubercular drugs, singly or in combination, have
      been encapsulated in polymers to provide controlled drug release and the system
      also offers the flexibility of selecting various routes of administration such as
      oral, subcutaneous and aerosol. The present review highlights the approaches
      towards the preparation of polymeric antitubercular drug delivery systems,
      emphasizing how the route of administration may influence drug bioavailability as
      well as the chemotherapeutic efficacy. In addition, the pros and cons of the
      various delivery systems are also discussed.

PMID- 16305384
TI  - Relevance of multidrug resistance proteins on the clinical efficacy of cancer
      therapy.
AB  - Variations in drug uptake and efflux, as well as changes in intracellular drug
      entrapment and distribution may represent important resistance mechanisms to
      cancer therapy. A variety of ATP binding cassette transporters (ABC) localised in
      multiple cell membranes is implied in those phenomena, representing a mechanism
      of protection of cells against xenobiotics. Many cancer cell lines over express
      some ABC transporters, especially p-glycoprotein, MRP1 and BCRP. This over
      expression is related to worse cancer treatment outcome and, in some cases,
      reduced overall survival of cancer patients. This paper reviews the location and
      physiological role of the three transporters mentioned and also describes the
      drugs that are substrates of these proteins. The usefulness of animal and
      cellular models to evaluate the role of these transporters on the uptake and
      efflux of anticancer drugs is discussed. Finally, the results of preclinical and
      clinical studies about the utility of some inhibitors of these pumps, as well as
      the implications of polymorphism of ABC transporters on the efficacy and safety
      of anticancer therapeutics are reported.

PMID- 16305385
TI  - Solvation of drugs as a key for understanding partitioning and passive transport
      exemplified by NSAIDs.
AB  - Passive transport properties of drug molecules are of utmost importance for their
      pharmacological and biopharmaceutical effectiveness. Diffusion in different media
      and through lipid bilayers is in many cases the rate-determining step for the
      distribution in the body. In the present review an attempt is made to demonstrate
      the importance of solvation of drug molecules for the diffusion and
      partition/distribution in phases of different lipophilicity. Different approaches
      known in the literature to describe solvation of compounds with flexible
      conformation are discussed as well as the experimental methods to directly
      measure the energy of solvation. NSAIDs are chosen as an example of a class of
      drugs of different molecular structures that have already been studied thoroughly
      in many aspects, and a set of aliphatic alcohols can be used as a model for
      compartments of different lipophilic/hydrophilic properties. Thermodynamic
      characteristics of solvation of the drug molecules yielded by independent
      classical experimental methods (Gibbs energy, enthalpic and entropic terms of
      Gibbs energy) are studied in order to better understand diffusion and
      distribution properties. Correlations between in-vitro-data (partition
      coefficient, enthalpy of solvation) with biopharmaceutically relevant
      characteristics (plasma half-life) are also discussed.

PMID- 16305386
TI  - Synthesis of chitosan microspheres containing pendant cyclodextrin moieties and
      their interaction with biological active molecules.
AB  - A new route to obtain chitosan derivatives containing cyclodextrin moieties as
      pendant groups was developed. The chitosan microspheres, obtained through
      crosslinking with glutaraldehyde of an acetic acid solution of chitosan, in an
      organic suspension medium, were reacted with chloroacyl cyclodextrins in organic
      basic solvents. The acyl cyclodextrin moieties are linked to the chitosan
      microspheres through C-N bonds, with the elimination of HCl; higher amounts of
      acyl cyclodextrin are linked to the microspheres with a smaller crosslinking
      degree. The chitosan-cyclodextrin conjugates retain higher amounts of bioactive
      substances (nalidixic acid, piroxicam) or of p-nitrophenol (model substance) than
      their parent chitosan supports, both by ionic forces and by the formation of
      inclusion complexes in the cyclodextrin inner cavities. After these preliminary
      studies, one can appreciate that the cyclodextrin-chitosan conjugates could be
      used as supports for chromatographic separations or controlled release drug
      systems.

PMID- 16305387
TI  - Targeting intracellular targets.
AB  - Many therapeutic agents have intracellular compartments as their site of action.
      Targeted delivery of these agents to their specific intracellular targets could
      result in enhanced therapeutic efficacy and reduced toxicity. Various carriers
      have been shown useful in targeted delivery of different classes of therapeutic
      agents. Among these carriers, biodegradable nanoparticles formulated from
      biocompatible polymers poly(D,L-lactide-co-glycolide) (PLGA) and polylactide
      (PLA) have shown the potential for sustained intracellular delivery of different
      therapeutic agents. In this review, we discuss different intracellular targets,
      barriers to intracellular delivery, mechanism and pathways of intracellular
      delivery, and various carriers and approaches that have been investigated for
      intracellular drug delivery.

PMID- 16305388
TI  - Chronotherapeutic approach to design a thermoresponsive membrane for transdermal
      drug delivery.
AB  - In this review, the concepts of chronobiology, circadian rhythm,
      chronopharmacology, homeostasis and chronotherapy are taken into account to
      approach the optimal drug therapy, in which the timing of drug administration
      plays an important role. Based on these considerations, our laboratory has
      developed a thermo-responsive membrane by entrapping a single or binary liquid
      crystal to achieve an on-off switching drug delivery for transdermal application
      via the externally repeated cycle of temperature change, which may simulate the
      dosing time of therapeutic needs for human body.

PMID- 16305389
TI  - Controlled release of protein from hydrocolloid gel microbeads before and after
      drying.
AB  - Casein entrapped within gel microbeads using alginate, amidated LM pectin, gellan
      gum and a system containing a mixture of these polysaccharides
      (pectin:gellan:alginate, 1/3: 1/3: 1/3), were obtained by ionic gelation in a
      high-pressure capillary apparatus. Hydrogenated vegetable fat was also added to
      produce the gel microbeads and protein release in all the systems was measured,
      including from freeze-dried capsules containing protein and fat. Encapsulation
      efficiency, capsule size and morphology were evaluated as well as the protein
      release profile. Encapsulation efficiencies from 83.7 to 90.7% were obtained for
      the protein capsules and from 71.8 to 95.4% for those containing protein and fat.
      Greater release was observed from gel microbeads without fat where alginate
      presented the greatest diffusion (100%) and the system with a mixture of
      polyssacharides, the best barrier, with protein retention of 90% after 240 min in
      solution. The fat containing gel microbeads presented good percent retentions and
      both the gel microbeads and the dry microbeads showed similar percentages for
      release. The majority of the systems studied showed a burst effect on release.
      Gel microbeads size distribution was similar, both with and without fat, and
      independent of the matrix material, the mean size being 150microm. The
      morphological observations showed that the gel microbeads were spheroidal with a
      homogenous distribution of fat droplets in the microcapsules. Agglomeration
      occurred on drying but many particles maintained a partially spheroidal form,
      with a configuration of solid material.

PMID- 16305390
TI  - A review on the molecular mechanisms involved in the placental barrier for drugs.
AB  - The placenta has traditionally been considered as a highly permeable organ for a
      large variety of substances with diverse molecular structures that are readily
      able to cross it from the maternal blood to reach the foetus. This has
      recommended limiting the use of drugs during pregnancy as far as possible.
      However, our present knowledge points to the existence of different systems,
      including plasma membrane carriers, biotransforming enzymes, and export pumps,
      that determine the selectivity and efficacy of the so-called placental barrier. A
      good understanding of the molecular bases of these processes and their regulation
      is crucial: i) to predict interactions between drug-drug, drug-endogenous
      substances and drug-food components, ii) to analyse the relevance of
      polymorphisms in the inter-individual variability of conceptus sensitivity to
      drugs, and iii) to develop novel pharmacological strategies aimed at delivering
      medicinal drugs to pregnant women, simultaneously minimising the risk of foetal
      exposure to active agents, and to specifically target drugs to the placenta
      and/or foetus. The present review does not attempt to offer a complete list of
      the available medicinal compounds and their ability to cross the placenta but
      instead to provide the reader with an up-to-date overview of the mechanisms
      involved in carrying out or preventing the transfer of active drugs across the
      placenta.

PMID- 16305391
TI  - Drug delivery to captive Asian elephants - treating Goliath.
AB  - Captive Asian elephants have been maintained in captivity by humans for over 4000
      years. Despite this association, there is little published literature on the
      treatment of elephant diseases or methods of drug administration to these
      animals. Elephants in captivity are generally healthy and require few therapeutic
      interventions over the course of their lifetime. However, when they become
      acutely ill, treatment becomes a serious issue. The successful and consistent
      administration of therapeutics to elephants is formidable in an animal that
      presents significant limitations in drug delivery options. The single most
      important factor in administering drugs to an elephant is the animal's
      cooperation in accepting the medication. Working around elephants can be very
      dangerous and this is magnified when working around sick or injured animals where
      the elephant is subject to increased stress, pain, and unusual situations
      associated with treatment. The large body size of the Asian elephant produces a
      separate set of issues. In this paper, methods of drug administration and their
      associated limitations will be reviewed. Considerations of medicating such large
      animals can serve to highlight the problems and principles of treatment that are
      inherent in these species.

PMID- 16305392
TI  - Drug delivery systems using immobilized intact liposomes: a comparative and
      critical review.
AB  - Liposomes sustain considerable interest to develop ways to fabricate drug
      delivery systems that would provide a good release without inducing any systemic
      reactions into the host. However, in many cases, liposomes injected into the
      blood stream are rapidly cleared from the system and only a fraction reaches the
      target site even when poly(ethylene glycol) (PEG)-coated liposomes are used.
      Composite drug delivery systems with liposomes i.e., liposomes linked to other
      substrates can be good candidates for certain type of drug release to achieve a
      localised treatment. This paper reviews the fundamental phenomena of the
      interactions between liposomes and solid substrates. Then, we address various
      techniques that have been used to immobilize intact liposomes onto and into
      different substrates. Finally, properties of liposomes used as drug delivery
      systems are briefly reviewed.

PMID- 16305393
TI  - In vitro evaluation of a hydroxypropyl cellulose gel system for transdermal
      delivery of timolol.
AB  - In this work, the development of a gel reservoir for a timolol (TM) transdermal
      iontophoretic delivery system is investigated. TM gel is prepared using
      hydroxypropyl cellulose (HPC) and the permeability of TM from the gel through an
      artificial membrane (Polyflux) and pig stratum corneum (SC) is studied. For a
      constant TM donor concentration, the TM transport across the Polyflux membrane
      alone decreases when the concentration of the gel increases due to increase of
      the gel viscosity. For constant gel concentration, however, the TM permeation
      across the membrane increases when the TM donor concentration increases. In
      addition, no effect of the electrical current (iontophoresis, current density 0.5
      mA cm-2) on the TM permeation is found. For the combination of the Polyflux
      membrane with pig SC, the TM transport is much lower than for the membrane alone
      and the SC fully controls the TM delivery. In this case, the application of
      electrical current enhances the TM delivery 13-15 times in comparison to passive
      (no current) transport. According to our estimation, the daily TM dose (10-60 mg)
      can be delivered by an iontophoretic patch with Polyflux membrane area of 6-36
      cm2 containing 20% (w/w) HPC gel and 15 mg cm-3 of TM.

PMID- 16305394
TI  - Pegylated poly(lactide) and poly(lactide-co-glycolide) nanoparticles:
      preparation, properties and possible applications in drug delivery.
AB  - The preparation, properties and potential applications in drug delivery of
      biocompatible and biodegradable PLA-PEG and PLGA-PEG nanoparticles are discussed.
      PLA-PEG and PLGA-PEG nanoparticles have been produced by emulsification-solvent
      evaporation, solvent displacement and salting out methods. The nanoparticles can
      be stored as freeze-dried powders, but an adequate amount of a suitable
      lyoprotectant should be added prior lyophilisation to prevent nanoparticle
      aggregation and retain nanoparticle redispersibility. The nanoparticles have a
      core-shell structure with a PLA core and a PEG coating. Their basic colloidal
      properties and degradation depend on copolymer composition. The PLA-PEG and PLGA
      PEG nanoparticles exhibit prolonged blood circulation following intravenous
      administration to animals. The composition of the nanoparticles determine their
      biodistribution properties, probably through its effects on the effectiveness of
      the PEG steric barrier and the size of the nanoparticles. The ability of the PLA
      PEG and PLGA-PEG nanoparticles to evade rapid phagocytocis has extended the range
      of sites within the body that the nanoparticles can reach, which has significant
      implications with regard to their application in controlled drug delivery and
      targeting. The PLA-PEG and PLGA-PEG nanoparticles can be loaded with a variety of
      bioactive agents achieving satisfactory loading, especially in the case of
      hydrophobic drugs. The nanoparticles have been investigated for the treatment of
      infectious diseases and cancer, the intravenous and mucosal delivery of proteins,
      and oligonucleotide and gene delivery. The results have been encouraging and PLA
      PEG and PLGA-PEG nanoparticle formulations, improving the therapeutic potential
      of both established and new drugs, may be expected to be available in the near
      future.

PMID- 16305396
TI  - Quinone bioreductive prodrugs as delivery agents.
AB  - Quinone bioreductive prodrugs were developed to target the hypoxic or the
      reductase- rich population of solid tumours. The mechanism of their selective
      activation is based on their ability to convert the quinone sub-structure to
      their activated semiquinone or hydroquinone species affording the active species.
      Recent studies on their biochemical activation process have resulted in their
      development as delivery agents that can effectively release a potent (but not
      necessarily a cytotoxic) agent under hypoxic/reductive conditions. This
      technology platform is currently being used to design/identify, and synthesise
      novel quinone bioreductive delivery agents to target cancer and other diseases
      where hypoxia and/or reductive enzymes play a major pathophysiological role.

PMID- 16305395
TI  - HIV-1 Vpr: enhancing sensitivity of tumors to apoptosis.
AB  - Cancers can adapt several evasive functions including apoptosis evasion, self
      sufficiency in growth signals, insensitivity to anti-growth signals, sustained
      angiogenesis, limitless replication potential, tissue invasion and metastasis.
      The invariable hurdle for development of therapies against such aberrant
      conditions requires both selective and potent cytotoxicity. Analysis of HIV-1
      Vpr's apoptotic and anti-proliferative activity have revealed potentially
      important implications for cancer therapy. Accordingly, we have reviewed the
      properties of Vpr that will likely contribute to its efficacious function as an
      anti-tumor agent. Among these are its ability to induce cell cycle arrest,
      inhibit inflammation, provoke p53 independent apoptosis, and selective killing of
      rapidly dividing cells.

PMID- 16305397
TI  - Role of cyclodextrins in ophthalmics.
AB  - Cyclodextrins are oligosaccharides having outer hydrophilic surface and central
      hydrophobic cavity. These agents form inclusion complexes with poorly water
      soluble drugs; hence they show an important implication for use in ophthalmics
      because of their applications in solubilising and stabilising the ocular drugs.
      Most of the drugs being used in ophthalmics were not tailor-made for the eye and
      considering the poor bioavailability of <1% from the corneal surface,
      presentation of the drug in a soluble form and at high concentration is
      important. Provision of a high drug concentration at the corneal surface
      increases the percent drug permeation indicating the usefulness of cyclodextrins
      as penetration enhancers. A decrease in irritation potential of some drugs upon
      incorporation of cyclodextrins is also reported. Polymer-cyclodextrin
      multicomponent systems further extend the role of cyclodextrins in improving the
      solubility and bioavilability of ocular drugs. Large hydrophilic cyclodextrins
      like hydroxypropyl-beta-cyclodextrin and sulphobutylether-beta-cyclodextrin are
      safe for the use in aqueous eye drop solutions especially since they do not cross
      the lipophilic cornea. Various aspects about the applications of cyclodextrins in
      ophthalmics, the formulation considerations and expected toxicity of
      cyclodextrins (especially if high concentration is used) is discussed in this
      review. Strategies like use of polymers to reduce the effective concentration of
      cyclodextrin required without compromising solubility are also included. Further
      the concept of incorporating the drug-cyclodextrin complexes into liposomes or
      niosomes for a better targeting of the drug at appropriate tissue destination is
      discussed as a possible future option.

PMID- 16305398
TI  - Drug delivery across the blood-brain barrier.
AB  - The brain is protected and isolated from the general circulation by a highly
      efficient blood-brain barrier. This is characterised by relatively impermeable
      endothelial cells with tight junctions, enzymatic activity and active efflux
      transport systems. Consequently the blood-brain barrier is designed to permit
      selective transport of molecules that are essential for brain function. This
      creates a considerable challenge for the treatment of central nervous system
      diseases requiring therapeutic levels of drug to enter the brain. Some small
      lipophilic drugs diffuse across the blood-brain barrier- sufficiently well to be
      efficacious. However, many potentially useful drugs are excluded. This review
      provides an insight into the current research into technologies to target small
      molecules, peptides and proteins to the brain. A brief review of the nature of
      the blood-brain barrier and its transport mechanisms is provided. Strategies to
      target and improve transport across the blood-brain barrier include the prodrug
      lipidisation approach, sequential metabolism chemical delivery systems, drug
      vectors, liposomes and nanoparticles. Included is the discussion of techniques to
      minimise clearance from the circulation by the reticuloendothelial system in
      order to extend circulation residence time and optimise the opportunity for
      interaction between the drug delivery system and the blood-brain barrier.

PMID- 16305399
TI  - Polymeric radiotracers in nuclear imaging.
AB  - Water-soluble polymers have been used in the last two decades to modify the
      pharmacokinetics and physicochemical properties of targeted therapeutic agents.
      Non-invasive imaging techniques such as nuclear imaging can be used to assess the
      drug delivery efficiency of novel formulations in a cost-effective fashion and
      thereby facilitate their development process. Polymeric radiopharmaceuticals have
      also been investigated on their own right as potential nuclear imaging agents.
      Clinical applications of polymeric radiopharmaceuticals include blood-pool
      imaging and targeted molecular imaging. In the latter case, water-soluble
      polymers are often used to modify the pharmacokinetics and biodistribution
      pattern of ligands that target receptors or antigens at disease sites. As
      advances are continue to be made in the emerging field of molecular imaging,
      nuclear imaging will play an increasingly important role in the development of
      polymeric drug delivery systems. Similarly, polymer technology will also be
      integrated into the development of molecularly targeted radiopharmaceuticals.
      Here, we review various aspects of polymeric radiotracers and their applications
      in nuclear imaging.

PMID- 16305400
TI  - Mucosal immunisation: adjuvants and delivery systems.
AB  - The mucosal administration of vaccines is an area currently receiving a high
      level of interest due to potential advantages offered by this technique. These
      advantages include the ability to administer vaccines without need for needles,
      thus improving patient compliance with vaccination schedules, and the capacity to
      induce immune responses capable of preventing infections at the site of
      acquisition. Despite these advantages a number of limitations exist which
      currently inhibit our ability to successfully develop new mucosal vaccines. As
      such, much research is currently focused on developing new adjuvants and delivery
      systems to overcome these difficulties. However, despite high levels of interest
      in this area, relatively few mucosal vaccine candidates have successfully
      progressed to human clinical trials. In the review that follows, we aim to
      provide the reader with an overview of the immune system with respect to
      induction of mucosal immune responses. Furthermore, the review provides an
      overview of a number of microbial (bacterial toxins, CpG DNA,
      cytokines/chemokines, live vectors, and virus like particles) and synthetic
      (microspheres, liposomes, and lipopeptides) strategies that have been
      investigated as adjuvants or delivery systems for mucosal vaccine development,
      with a focus on the delivery of vaccines via the oral route.

PMID- 16305401
TI  - Skin lipid synthesis inhibition: a possible means for enhancing percutaneous
      delivery of levodopa.
AB  - Skin perturbation with ethanol followed by application of beta-chloroalanine
      (beta-CA) or atorvastatin (AVN) was employed for delaying the recovery of
      sphingosine (a precursor of ceramide) and cholesterol, respectively in epidermis
      of rats. Dose optimization studies revealed 600 microg of beta-CA and 750 microg
      of AVN significantly (p<0.05) inhibited the synthesis of sphingosine and
      cholesterol, respectively and prevented their replenishment to normal levels till
      48 hr in viable rat skin. Co-application of calcium chloride (0.1 mM) inhibited
      the synthesis of both micro constituents of epidermis to a greater magnitude,
      whereas verapamil reduced this effect. The in vitro permeation of levodopa across
      treated skin portions was directly correlated with percentage of sphingosine and
      cholesterol inhibited by the treatments. The in vitro permeation of levodopa
      across skin excised after treatment with beta-CA or AVN was enhanced 3-fold.
      Effective plasma concentration (1.58 microg/ml) of levodopa in rats was achieved
      within 2 hr and maintained till 12 hr after AVN treatment, and increased to 36 hr
      with the co-application of calcium chloride. However, when the skin was treated
      with beta-CA, Ceff was achieved after 4 hr and was maintained till 36 hr. The
      inclusion of calcium chloride maintained Ceff for 48 hr. Hence, synthesis
      inhibition of skin lipids seems to offer a feasible means to enhance the systemic
      delivery of polar drugs like levodopa.

PMID- 16305402
TI  - Dose sparing of CpG oligodeoxynucleotide vaccine adjuvants by nanoparticle
      delivery.
AB  - The main objective of these studies was to investigate whether the nanoparticle
      delivery has any immunopotentiation effect at modest doses of a few micro- or
      nanograms of CpG oligodeoxynucleotide (CpG ODN) and what would be the influence
      on T cell responses at such low doses. Various doses (5 to 0.05 microg) of a
      model CpG ODN adjuvant (#1826) along with 2 Lf tetanus toxoid (TT) were
      formulated in either nanoparticles using poly(D,L-lactic-co-glycolic acid) (PLGA)
      50:50 co-polymer, or saline. Strong antigen specific ex vivo T cell proliferation
      was observed for the Balb/c mice receiving immunogens in nanoparticles. At 5
      microg dose of CpG ODN, the T cell stimulation index (SI) was 241 as compared
      with 74 for the same dose when given in saline. Comparable SI value of 78 was
      observed at 100-fold lower dose (0.05 microg) using nanoparticles. Similarly,
      significantly higher (P<0.01) cytokine secretion was observed for nanoparticles
      groups. A ten-fold lower dose (0.5 microg instead of 5 microg) of CpG ODN in
      nanoparticles was adequate to obtain levels of IFN-gamma, TNF-alpha, and IL-2
      comparable to those observed following immunisations in saline. The
      immunopotentiation effect of the particulate delivery on antibody response (total
      IgG and subtypes) was not so marked. These studies emphasise that antigen
      delivery in biodegradable nanoparticles can facilitate induction of strong T cell
      responses, particularly of the Th1 type, at extremely lower doses of CpG ODN.
      Such reduction in the effective dose would be advantageous for minimising the
      potential side effects of these novel adjuvants.

PMID- 16305403
TI  - Influence of formulation and excipient variables on the pellet properties
      prepared by extrusion spheronization.
AB  - Four commercial grades of microcrystalline cellulose, Avicel PH 101, Avicel PH
      102, Avicel PH 112 and Avicel PH 302 were compared for extrusion spheronization.
      Model mixes containing Avicel PH 101 with different proportions of fillers like
      lactose and dicalcium phosphate dihydrate (DCPD) were also compared to observe
      the influence of these fillers on the pellet properties. The amount of water used
      for granulation of Avicel/ Avicel mixes was kept constant so as to evaluate and
      quantitate the influence of these excipients/fillers on the pellet properties.
      The various pellet properties evaluated included, drug release, size and size
      distribution, shape, density, friability and flow. Mean pellet diameter did not
      vary among the Avicel grades. Pellets prepared with different proportions of
      Avicel PH 101 and lactose were more or less similar in mean diameter. The same
      phenomena were observed in case of DCPD as well. Plain lactose pellets were the
      largest in size. Therefore, it can be inferred that the presence of Avicel
      suppressed the change in pellet size. Circularity was found to be significantly
      linear function of log of bulk density of Avicel powders. As revealed by the SEM
      photographs, pellets of Avicel PH 101 were fairly round where as those containing
      Avicel PH 302 were dumbbell shaped. Formulations containing DCPD showed the
      highest circularity. Drug release rate varied in all the formulations. Among the
      Avicel grades, Avicel PH 302 showed the highest drug release rate where as Avicel
      PH 101 showed the least. Drug release also varied as a function of the type of
      filler and their proportion in the pellets. For both the fillers, the drug
      release increased with an increase in their proportion. Less water was required
      for formulations containing higher amounts of lactose and DCPD. Plain DCPD failed
      to spheronize, although pellets of plain lactose could be formed at the
      investigated level of water.

PMID- 16305404
TI  - Intestinal absorption enhancement via the paracellular route by fatty acids,
      chitosans and others: a target for drug delivery.
AB  - Peroral delivery of hydrophilic drugs is one of the greatest challenges in
      biopharmaceutical research. Hydrophilic drugs usually present low bioavailability
      after oral administration. One of the causes of this low bioavailability is their
      poor intestinal permeation through the paracellular pathway. This pathway is
      actually restricted by the presence of tight junctions at the apical side of the
      enterocytes. In the last few years, great interest has been focused on the
      structure and cellular regulation of tight junctions, materializing in more in
      depth knowledge of this intestinal barrier. Simultaneously, and on the basis of
      this understanding, continuous efforts are being made to develop agents that can
      modulate tight junctions and magnify the paracellular permeability of hydrophilic
      compounds without causing significant intestinal damage. This review focuses on
      strategies to improve the paracellular permeation of poorly absorbed drugs as a
      way to enhance their bioavailability after oral administration. Most of the
      research on this subject has been carried out using in vitro models (mainly Caco
      2 cell monolayers), which yield useful information on the potential effects and
      mechanisms of action of absorption-enhancing compounds. However, in vivo studies,
      which are much more scarce, are needed to confirm the effects of potential
      enhancers and to evaluate the suitability of including these compounds as
      excipients in drug formulation. We review the in vitro and in situ studies
      involving the most promising paracellular permeation enhancers (e.g., medium
      chain fatty acids and chitosan and its derivatives), analyzing the degree of drug
      absorption enhancement achieved, as well as the potential associated toxicity.
      The few studies performed in vivo are also presented. In addition, the findings
      of recent absorption enhancers, such as zonula occludens toxin or thiolated
      polymers, are reviewed.

PMID- 16305405
TI  - Transdermal drug delivery: penetration enhancement techniques.
AB  - There is considerable interest in the skin as a site of drug application both for
      local and systemic effect. However, the skin, in particular the stratum corneum,
      poses a formidable barrier to drug penetration thereby limiting topical and
      transdermal bioavailability. Skin penetration enhancement techniques have been
      developed to improve bioavailability and increase the range of drugs for which
      topical and transdermal delivery is a viable option. This review describes
      enhancement techniques based on drug/vehicle optimisation such as drug selection,
      prodrugs and ion-pairs, supersaturated drug solutions, eutectic systems,
      complexation, liposomes, vesicles and particles. Enhancement via modification of
      the stratum corneum by hydration, chemical enhancers acting on the structure of
      the stratum corneum lipids and keratin, partitioning and solubility effects are
      also discussed. The mechanism of action of penetration enhancers and retarders
      and their potential for clinical application is described.

PMID- 16305406
TI  - In vivo pharmacokinetic and tissue distribution studies in mice of alternative
      formulations for local and systemic delivery of Paclitaxel: gel, film, prodrug,
      liposomes and micelles.
AB  - The aim of this study was to increase the understanding on the pharmacokinetic
      and tissue distribution of paclitaxel as influenced by formulation approach. For
      this purpose, various formulations investigated in Swiss mice included liposomes,
      poloxamer 407 gel and chitosan film for subcutaneous route; and water-soluble
      methacrylate prodrug, liposomes and poloxamer micelles for systemic
      administration. During this study, the currently marketed formulation of
      Cremophor EL of paclitaxel was used as the reference. A highest plasma
      concentration following intravenous administration of paclitaxel was observed for
      rigid and 'Stealth((R))' liposomes containing the prodrug while, least was for
      covalently incorporated paclitaxel micelles. Further, poloxamer micelles
      demonstrated both the highest mean residence time of 7.34 h and volume of
      distribution (VSS=4.82 and VZ=5.87 L/kg) for paclitaxel. This was followed by
      prodrug loaded 'Stealth' liposomes, which showed a mean residence time of 4.96 h
      but were least distributed into apparent physiological volume (VSS=2.12 and
      VZ=3.16 L/kg). These results clearly signify the role of formulation/excipient in
      drug disposition and possible interactions. Importantly, due to decrease in the
      clearance rate of drug, the area under curve values of paclitaxel increased by
      1.64- and 2.5-fold for micellar and prodrug loaded 'Stealth' liposomal
      formulations, respectively over reference formulation. While thermoreversible
      gels served to decrease plasma concentration of paclitaxel (8-fold) after
      subcutaneous administration, systemic levels were totally absent after
      implantation of films. In tissue distribution studies, maximum percent of
      paclitaxel was observed in liver for reference formulation, conventional
      liposomes and micelles whereas highest levels of prodrug and 'Stealth((R))'
      liposomes were in kidney and spleen, respectively. The novel formulations
      significantly altered tissue accumulation profiles of paclitaxel relative to the
      reference formulation, for example, reduction in uptake by heart from liposomes
      and micelles, as well as the major recognition mechanism for elimination. It is
      proposed that a combination therapy with liposomes and micelles of paclitaxel for
      systemic delivery along with implantation of chitosan film for local delivery,
      may serve not only to improve patient compliance by obliterating the need to
      administer Cremophor EL, but also increase patient survival.

PMID- 16305407
TI  - Comparative study of different silymarin formulations: formulation,
      characterisation and in vitro/in vivo evaluation.
AB  - The aim of the present study was to study the synergistic hepatoprotective effect
      of silymarin with phospholipids when it is encaged in microspheres so as to
      passively target it to liver and to compare these silymarin formulations with
      silymarin solution. Various silymarin loaded lipid emulsions were formulated
      which include formulation A prepared with soyabean oil as an internal oily phase,
      soya lecithin as surfactant and tween 80 as cosurfactant; formulation B which was
      same as formulation A but was filtered through 0.45 micro membrane filter and
      finally steam sterilized for intravenous administration; formulation C containing
      soyabean oil as an internal oily phase, soya lecithin as surfactant, tween 80 and
      propylene glycol as cosurfactant/ cosolvent. These formulations were compared for
      their release profile with silymarin solution in propylene glycol, i.e.
      formulation D. In vivo evaluation was carried out using three models i.e.
      phenobarbitone induced sleep time in mice, biochemical estimation of SGOT and
      SGPT enzyme levels and histopathological examination of rat livers. Results
      revealed that there was significant reduction in sleep time in the mice treated
      with silymarin loaded lipid microspheres (both p.o. as well as i.v.) when
      compared with control and even with plain lipid microspheres and silymarin
      solution and significant reduction in enzyme levels in silymarin lipid
      microspheres treated group when compared with control, plain lipid microspheres
      as well as silymarin solution treated group. Histopathological studies also
      supported the results obtained from the other two models. A positive outcome of
      these studies gave an insight that if silymarin is coupled with phospholipid in
      such microparticulate delivery systems, hepatoprotective effect of drug molecules
      can be pronounced further by self targeting nature and synergistic action.

PMID- 16305408
TI  - High performance gene delivery polymeric vector: nano-structured cationic star
      polymers (star vectors).
AB  - Nano-structured hyperbranched cationic star polymers, called star vectors, were
      molecularly designed for a novel gene delivery non-viral vector. The linear and
      3, 4 or 6 branched water-soluble cationic polymers, which had same molecular
      weight of ca. 18,000, were synthesized by iniferter (initiator-transfer agent
      terminator)-based photo-living-radical polymerization of 3-(N,N
      dimethylamino)propyl acrylamide, initiated from respective multi-dithiocarbamate
      derivatized benzenes as an iniferter. All polymers produced polyion complexes
      'polyplexes' by mixing with pDNA (pGL3-control plasmid), in which the particle
      size was ca. 250 nm in diameter [the charge ratio < 2/1 (vevtor/pDNA)] and ca.
      150 nm (the charge ratio > 2.5/1), and the zeta-potential was ca. +10 mV (the
      charge ratio > 1/1). When COS-1 cells were incubated with the polyplexes 12 h
      after preparation under the charge ratio of 5/1, higher gene expression was
      obtained as an increase in branching, with a little cytotoxicity. The relative
      gene expression to the linear polymer was about 2, 5, and 10 times in 3-, 4-, and
      6-branched polymers, respectively. The precise change in branching of polymers
      enabled the control of the gene transfer activity.

PMID- 16305409
TI  - New prospects for glycopeptide based analgesia: glycoside-induced penetration of
      the blood-brain barrier.
AB  - Antinociceptive effects and BBB transport properties of glycosylated enkephalin
      derivatives are reviewed. Previously, the application of enkephalins as
      analgesics has been retarded by their poor stability in vivo and by their
      inability to effectively penetrate the blood brain barrier. This shortcoming has
      been overcome by glycosylation, paradoxically leading to enhanced BBB transport
      via transcytosis. Principal design considerations required for enhanced binding,
      stability and transport of opioid peptides are reviewed. Modifications of the
      peptide backbone and side chains to achieve optimal receptor binding (micro/delta
      selectivity) are presented. The importance of reversible binding between the
      glycopeptide and membranes is emphasized, and several pertinent examples of
      peptide-membrane interactions are discussed in the light of glycopeptide
      transport and opioid binding. An "amphipathic hypothesis" is introduced as a
      rationale for the observed BBB penetration of the opioid glycopeptides.

PMID- 16305410
TI  - Preparation and characterization of water-soluble prodrug, liposomes and micelles
      of Paclitaxel.
AB  - Alternative formulations of paclitaxel were developed in order to improve its
      aqueous solubility, and characterized in vitro. A methacrylic acid based
      nanoconjugate of paclitaxel was synthesized by a simple esterification reaction
      with molecular weight of 1657 Da. The in vitro hydrolysis study on the prodrug of
      paclitaxel in presence of rat plasma has shown that the ester bond was quite
      stable (less than 1% of paclitaxel was liberated from prodrug in 24 h). This
      water-soluble prodrug was encapsulated into polyethylene glycol coated liposomes
      optimized with saturated lipids, to overcome the physical instability associated
      with paclitaxel. Under in vitro testing, prodrug liposomes seem very impressive
      with release of only 45% of payload in 180 h. Further, chemical as well as
      physical stability studies have shown that liposomes were stable without any
      signs of crystallization of paclitaxel. In addition, paclitaxel was covalently
      coupled to poloxamer via methacrylic acid linker to obtain a micelle forming
      conjugate. Evidence for self-assembly of this conjugate into micelles was
      provided by fluorescence spectroscopy, light scattering and differential scanning
      calorimetry techniques. Micellization of the conjugate was thermodynamically
      favored and the core of resulting micelles exhibited higher microviscosities
      (than poloxamer micelles). Release studies using dialysis technique along with
      high performance liquid chromatography revealed that paclitaxel is liberated from
      micelle in the form of methacrylic acid oligomer based prodrug in a gradual
      manner. These preliminary studies provided indication on the performance and
      feasibility of testing these carrier systems as a safer alternative to the
      Cremophor EL based paclitaxel formulation.

PMID- 16305411
TI  - Effect of vinblastine on transfection: influence of cell types, cationic lipids
      and promoters.
AB  - As previously shown, vinblastine, when incorporated into a cationic lipid prior
      to generation of lipoplexes, increases by approximately 30-fold the extent of
      transfection of pbeta-Gal with a cytomegalovirus promoter (pCMV-beta-Gal) to
      vascular smooth muscle cells (VSMC) by 1,2-dioleoyl-sn-glycero-3
      ethylphosphocholine (EDOPC)-pCMV-beta-Gal complexes. To test if this increase is
      limited to VSMC and EDOPC, or is general, we examined three other cell types,
      human umbilical artery endothelial cells (HUAEC), baby hamster kidney (BHK) cells
      and 293 cells derived from human kidney, as well as a different cationic lipid,
      1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). In addition, to determine the
      contribution of the NF-kappaB transcription factor to the vinblastine effect,
      pCMV was replaced with a smooth muscle gamma-actin gene promoter, SMGA, which,
      unlike pCMV, does not respond to NF-kappaB. It was found that on all cell types
      we tested, the transfection efficiency increased with vinblastine incorporation;
      however, the magnitude depended greatly on the cell type, e.g. whereas the
      transfection of VSMC increased approximately 30-fold, that of 293 cells increased
      only approximately 2-fold. The cationic phospholipid could be replaced with DOTAP
      with no loss of effect. In contrast, the promoter was critical and the
      stimulation was lost if pCMV was replaced with pSMGA. It is concluded that the
      positive effect of vinblastine on transfection is general and the stimulation of
      the transcription factor NF-kappaB is involved in this action. The activation of
      NF-kappaB by anti-microtubule agents should thus allow for transfection of
      specific cell types by vinblastine lipoplexes.

PMID- 16305412
TI  - Mathematical modelling and controlled drug delivery: matrix systems.
AB  - This paper deals with the physical and mathematical modelling description of drug
      release from matrix systems. In the introduction, matrix systems are considered
      in the wide frame of the controlled release systems and the concept of
      mathematical model is briefly discussed. Then, matrix structure and topology are
      matched, analysing the characteristics of the three-dimensional network
      constituting them. In this context, drug release mechanisms are considered with
      particular emphasis on the key factors ruling the release kinetics, such as
      matrix swelling, erosion, drug dissolution (re-crystallisation), drug diffusion,
      drug - polymer interaction, initial drug distribution and particle size
      distribution (for powdered matrix systems). The mathematical modelling section
      firstly considers the empirical and semi-empirical models that have the great
      advantage of showing analytical solutions. Then, the attention is focused on
      theoretical approaches regarding matrix swelling equilibrium and kinetics, drug
      dissolution, drug diffusion, drug - polymer interaction, initial drug
      distribution and matrix erosion. Finally, release kinetics from polydispersed
      spherical particles is studied. This review points out the fact that the
      comprehension of the phenomena ruling drug release from matrix systems is
      appropriate from both the physical and modelling point of view, although further
      improvements are always possible and desirable.

PMID- 16305413
TI  - Transdermal drug delivery of labetolol hydrochloride: system development, in
      vitro; ex vivo and in vivo characterization.
AB  - OBJECTIVE: The aim of the present work was to develop and evaluate matrix type
      transdermal drug delivery systems (TDDS) of labetolol hydrochloride (L-HCL)
      effective for 48 hours. EXPERIMENTAL: The TDDS were prepared by solvent
      evaporation technique. Six formulations (carrying Eudragit RL100:Eudragit RS 100
      in 7.5:4.5, 5.0:5.0, 3.5:8.5 in formulations X-1, X-2, X-3 and Eudragit RL100:PVP
      K-30 in 9.0:2.0, 5.0:5.0, 4.0:7.0 in formulations Y-1, Y-2, Y-3, respectively)
      were prepared. All formulations carried 36% w/w of L-HCL, 10-12% w/w of enhancer
      dimethyl sulfoxide and 2.5-7.5% w/w of plasticizer PEG 400 in methanol-acetone
      solvent system. The TDDS were evaluated by in vitro drug release, ex vivo skin
      permeation, stability and in vivo pharmacodynamic studies. RESULTS: The maximum
      drug release for X-series was 90.26% in 48 hours (X-1) and for Y-series, it was
      83.24% (Y-1). Again formulations X-1 (Kp = 0.221x10(-2) cm hr(-1)) and Y-1 (Kp =
      0.210x10(-2) cm hr(-1)) exhibited the best skin permeation potential in the
      respective series. This might be due to higher permeability characteristics of
      Eudragit RL100. A shelf life of 2.38 years was predicted for the TDDS. Mean
      systolic BP of the experimental hypertensive rats was significantly reduced
      (p<0.01) on TDDS treatment. CONCLUSION: The TDDS holds promise for clinical
      trials.

PMID- 16305414
TI  - Pharmaceutical aspects of hemoglobin-based oxygen carriers.
AB  - Oxygen delivery has evolved as a therapy of widespread interest in the clinical
      setting, especially in emergency medicine and anesthesiology. With the widespread
      recognition of blood-borne infections during the last two decades and the looming
      shortage of donor blood in future, efforts to formulate an artificial substitute
      for oxygen carrying capacity of RBCs have increased. Such blood substitutes,
      defined more correctly as oxygen therapeutics, are particularly valuable in
      circumstances such as war and trauma situations where properly matched blood may
      not be immediately available or is not accepted by the recipients for religious
      reasons. Several elegant formulations of hemoglobin, both free and encapsulated,
      have evolved recently and are collectively referred to as hemoglobin-based oxygen
      carriers (HBOCs). Few HBOCs have successfully entered into the clinical phase.
      This review discusses formulation requirements of HBOCs from a physiological
      viewpoint. Physico-pharmaceutical parameters, such as colloidal oncotic pressure,
      osmolality, viscosity, sterility, apyrogenicity and shelf-stability are
      traditionally a concern for large volume parenterals meant for resuscitation
      purposes. At the same time, properties such as oxygen affinity, hemoglobin
      content and in vivo efficacy of oxygen carriers are specific to HBOCs. Owing to
      the presence of a very active and functional protein (hemoglobin), requirements
      for adequate performance of HBOCs significantly differ from those of other large
      volume parenterals, such as lactated Ringer's solution, and plasma expanders,
      such as dextran or albumin solutions.

PMID- 16305415
TI  - Design, development and optimization of nimesulide-loaded liposomal systems for
      topical application.
AB  - Nimesulide, a non-steroidal anti-inflammatory drug, was incorporated into
      multilamellar liposomes to improve its performance on topical administration. The
      drug was loaded onto liposomes employing thin film hydration technique. Various
      process and formulation variables were investigated to obtain the liposomal
      products of desired quality. Liposomes were monitored for percent drug
      entrapment, after separating the unentrapped drug by mini column centrifugation,
      for vesicular properties (such as size distribution profile, morphological
      attributes and agglomeration tendency), drug diffused through synthetic
      semipermeable membrane, and drug leakage. Systematic optimization studies were
      carried out using 3(2) factorial design to select the optimized liposomal
      composition with reference to percent drug entrapment, drug diffusion and
      leakage. The optimized batch of liposomes was subjected to drug permeation and
      drug retention studies employing rat skin and human cadaver skin. In comparison
      to methanolic solution of pure nimesulide, liposomal formulations were found to
      retain higher amounts of nimesulide in the skin. Anti-inflammatory studies, using
      carragenan-induced rat paw edema model, indicated significantly better
      performance of liposomally entrapped nimesulide in comparison to the marketed gel
      formulation and the Carbopol gel containing nimesulide.

PMID- 16305416
TI  - In vitro and in vivo evaluation of guar gum-based matrix tablets of rofecoxib for
      colonic drug delivery.
AB  - The present study was carried out to develop and evaluate guar gum-based matrix
      tablets of rofecoxib for their intended use in the chemoprevention of colorectal
      cancer. Matrix tablets containing 40% (RXL-40), 50% (RXL-50), 60% (RXL-60) or 70%
      (RXL-70) of guar gum were prepared by wet granulation technique, and were
      subjected to in vitro drug release studies. Guar gum matrix tablets released only
      5 to 12% of rofecoxib in the physiological environment of stomach and small
      intestine. The matrix tablets RXL-40 disintegrated completely within 10 h in a
      dissolution medium without rat caecal contents (control study), and hence not
      studied further. When the dissolution study was continued in simulated colonic
      fluids (rat caecal content medium), the matrix tablets RXL-50 were acted upon by
      colonic bacterial enzymes releasing the entire quantity of drug wherein there was
      no appreciable difference when compared to that released in control study. The
      matrix tablets RXL-60 released another 88% of rofecoxib whereas matrix tablets
      RXL-70 released only 57% of rofecoxib in simulated colonic fluids indicating the
      susceptibility of the guar gum formulations to the rat caecal contents. The guar
      gum matrix tablets RXL-70 were subjected to in vivo evaluation in human
      volunteers to find their ability of targeting rofecoxib to colon. The delayed
      Tmax, prolonged absorption time (ta), decreased Cmax and decreased ka indicated
      that rofecoxib was not released significantly in stomach and small intestine, but
      was delivered to colon resulting in a slow absorption of the drug and making it
      available for local action in human colon.

PMID- 16305417
TI  - Intranasal drug delivery for brain targeting.
AB  - Many drugs are not being effectively and efficiently delivered using conventional
      drug delivery approach to brain or central nervous system (CNS) due to its
      complexity. The brain and the central nervous system both have limited
      accessibility to blood compartment due to a number of barriers. Many advanced and
      effective approaches to brain delivery of drugs have emerged in recent years.
      Intranasal drug delivery is one of the focused delivery options for brain
      targeting, as the brain and nose compartments are connected to each other via the
      olfactory route and via peripheral circulation. Realization of nose to brain
      transport and the therapeutic viability of this route can be traced from the
      ancient times and has been investigated for rapid and effective transport in the
      last two decades. Various models have been designed and studied by scientists to
      establish the qualitative and quantitative transport through nasal mucosa to
      brain. The development of nasal drug products for brain targeting is still faced
      with enormous challenges. A better understanding in terms of properties of the
      drug candidate, nose to brain transport mechanism, and transport to and within
      the brain is of utmost importance. This review will discuss some pertinent issues
      to be considered and challenges to brain targeted intranasal drug delivery. A few
      marketed and investigational drug formulations will also be discussed.

PMID- 16305418
TI  - Development of novel lyophilized mixed micelle amphotericin B formulation for
      treatment of systemic fungal infection.
AB  - The purpose of the study was to develop a stable, controlled release Amphotericin
      B (Amph B) lyophilized mixed micelle (MM) formulation using hydrogenated soya
      phosphatidylcholine (HSPC) and bile salts in monomeric form and evaluate it for
      therapeutic performance and side effects. The MM formulations of Amph B were
      prepared using sodium deoxycholate (NDC)/sodium taurocholate (NTC)/sodium cholate
      (NC), and HSPC. The optimization of bile salt: HSPC ratio in the MM formulation
      was done using 2(4) factorial designs. MM formulations were lyophilized using
      sucrose as a cryoprotectant and analyzed for per cent micelle yield, per cent
      drug loading and per cent entrapment efficiency. Comparative in vitro diffusion
      studies, hemolytic activity, and minimum inhibitory concentration (MIC) of
      developed MM formulations and marketed formulation (Fungizone) were evaluated
      using cellophane membrane, human red blood cells and Candida albicans
      respectively. In vivo studies of MM formulations were also carried out on Candida
      albicans infected white albino rats and compared with Fungizone. The optimized
      molar ratio of bile salt: HSPC was found to be 8:11. Among all MM formulations
      prepared, NDC/ HSPC formulation found to have maximum per cent drug loading
      (4.96+/-0.8%), per cent entrapment efficiency (93.2+/-1.5%) and per cent micelle
      yield (96.4+/-1.4%). The in vitro drug diffusion studies of developed MM
      formulations show close to zero-order diffusion kinetics. All MM formulations
      show improved therapeutic index and reduced side effects compared to reference
      formulation Fungizone. The NDC/HSPC MM formulation was found to have least
      hemolytic activity, MIC and mortality rate at all dosage levels. Improved
      antifungal activity and reduced toxicity of Amph B solubilized in MM may be due
      to higher cellular uptake of the drug by fungal cells of infected tissues from MM
      formulations. Hence, Amph B MM formulation could be a safe and effective viable
      alternative in the treatment of systemic fungal infections.

PMID- 16305419
TI  - Synthesis and in vitro skin permeation of naproxen conjugates with alpha
      alkylamino acids.
AB  - Novel amide conjugates of the NSAID naproxen (NAP, 1) with short-chain alpha
      alkylamino acids (C4 to C6 alkyl chain) were synthesized through a carbodiimide
      (EDAC)-assisted coupling reaction and evaluated as dermal prodrugs of NAP. The 2
      alpha-aminobutyl derivative (2) showed lipophilicity similar to that of NAP,
      while the higher homologues (3) and (4) were more lipophilic than the parent
      drug, as assessed by CLogP and HPLC methods. The chemical and enzymatic
      hydrolysis of these compounds was evaluated in aqueous buffer solution (pH 7.4)
      and 80% human plasma. All compounds showed a good chemical stability (t1/2 = 88
      133 h) but underwent a rapid enzymatic hydrolysis to NAP (t1/2 around 3 h). The
      bioconversion of prodrugs into NAP was confirmed by an in vivo test, since i.p.
      administration of compounds 2-4 to mice gave a similar analgesic response than
      the parent drug. In vitro skin permeation experiments were performed using adult
      human SCE samples mounted in Franz-type diffusion cells. The butyl derivative 2
      that showed an increased aqueous solubility compared to NAP gave a 5-fold
      improvement of skin permeation compared to NAP. In conclusion, the conjugate 2
      could be regarded as a good candidate to improve NAP topical delivery and will be
      further studied as a prodrug for topical administration of this drug.

PMID- 16305420
TI  - Oral delivery of insulin with the eligen technology: mechanistic studies.
AB  - The development of oral insulin using the eligen technology represents a
      significant advance in insulin administration which is expected to improve the
      quality of life of diabetic patients. As clinical studies progress, a great deal
      of interest has focused on the process by which this technology enables insulin
      absorption from the intestinal lumen into the bloodstream. The eligen technology
      employs low molecular weight compounds (termed drug delivery agents or carriers)
      which interact weakly and non-covalently with insulin, increasing its
      lipophilicity and thereby its ability to cross the gastrointestinal epithelium.
      In this study we investigated the mechanism of insulin absorption across caco-2
      cell monolayers with one of these drug delivery agents, N-[8-(2
      hydroxybenzoyl)amino] caprylate (SNAC). Our results show that SNAC increases
      insulin permeability approximately ten fold across cell monolayers and does so
      without affecting mannitol permeability or disrupting cell membranes. Confocal
      microscopy and immunocytochemistry revealed that insulin is transported
      transcellularly without detectable alteration of the tight junctions between
      adjacent cells. SNAC also appears to play some role in protecting insulin from
      proteolytic degradation, potentially allowing for more intact insulin to be
      available at the site of absorption.

PMID- 16305421
TI  - Decrease in Fungizone toxicity induced by the use of Lipofundin as a dilutent: an
      in vitro study.
AB  - The aim of this work was to develop an in vitro experimental protocol for the
      evaluation of toxicity and efficacy of an amphotericin B (AmB) micelle system,
      Fungizone, which was previously diluted with a lipid based emulsion for
      parenteral use, named Lipofundin LCT/MCT-20%. Two cell models were used for the
      experiments: Red Blood Cells (RBC) from human donnors and Candida tropicalis
      (Ct). These models were used to perform the toxicity and activity of the
      Fungizone/ Lipofundin admixture (AmB-LP) and the Fungizone (AmB-M) alone. While
      potassium (K+) and hemoglobin leakage from RBC were the parameters used to
      evaluate the acute and chronic toxicity, respectively, the efficacy of AmB-LP and
      AmB-M were assessed by K+ leakage or cell survival rate (CSR) from Ct. The
      results show that the toxicity of AmB-LP to RBC was concentration dependent
      concerning the K+ leakage; while at high concentrations, 5 and 50 mg x mL(-1),
      the leakage was 50.91 +/- 2.09% and 95.71 +/- 0.64%, respectively, at a
      concentration of 0.5 mg x mL(-1) this value was 17.16 +/- 1.57% and the value
      tended to zero for the lowest concentration studied, 0.05 mg x mL(-1).
      Surprisingly, AmB-LP induced very low hemoglobin leakage for all concentrations
      studied. At the highest concentration, 50 mg x mL(-1), this value was around 3%.
      When the cell model was Ct, the results changed completely. Not only high
      concentrations of AmB-LP, but also lower ones were able to induce a K+
      permeability of around 100%. The CSR parameter showed an inverse correlation with
      the concentration; high values, between 50 and 5 mg x mL(-1), resulted in a CSR
      of around 8%. On the other hand, for lower concentration values, 0.05 and 0.5 mg
      x mL(-1), this one was around 80%. The same profile of activity against Ct was
      found for AmB-M. Only a small variation was found for the K+ leakage at 0.05 mg x
      mL(-1) that presented a value of 96.99 +/- 2.53%. However, AmB-M seemed to be
      much more toxic than AmB-LP. Its induction of hemoglobin leakage started at 0.5
      mg x mL(-1) and reached the 100% at 5 mg x mL(-1). K+ leakage results were worse.
      The intermediate concentrations of study, 0.5 and 5 mg x mL(-1), presented a
      significant increase compared to AmB-LP. All together these results reveal that
      the activity of AmB is not only concentration dependent, but also depends on the
      drug carrier in which this compound was inserted. The AmB-LP preparation showed
      the same efficacy as AmB-M, but with a low toxicity. Therefore, AmB-LP presented
      a higher therapeutic index that permits the administration of high concentration
      of AmB without revealing side effects. However, the simple mixture of two complex
      pharmaceutical entities, as micelles and emulsions, should be analyzed carefully
      to assure that physicochemical stability is not reduced and thereby cause a
      different biodistribution in vivo.

PMID- 16305422
TI  - Photo-control of the polyplexes formation between DNA and photo-cation
      generatable water-soluble polymers.
AB  - Photo-cation generatable water-soluble polymers (Mw: approximately 1x10(5)) were
      prepared by radical copolymerization of N,N-dimethylacrylamide and vinyl monomer
      of triphenylmethane leucohydroxide (malachite green), which generate a cation
      upon ultraviolet light (UV) irradiation at wavelengths of between 290 and 410 nm.
      The malachite green contents of the copolymers were 3.6 (0.4 mol%), 7.9 (0.7
      mol%), and 15.0 (2.7 mol%) per molecule. When an aqueous solution of the photo
      cationized copolymers generated by UV irradiation was mixed with a Tris-HCl
      buffer (pH 7.4) of DNA (pGL3-control plasmid), dynamic light scattering (DLS)
      measurements showed the formation of polyplexes between the cationic copolymers
      and anionic DNA by non-specific electrostatic interaction, which was visualized
      with a confocal laser scanning microscopy (CLMS). Their mean cumulant diameter
      was about 150 nm with low polydispersity irrespective of the malachite green
      content in the copolymers. In the copolymer with the lowest malachite green
      content, almost all of the amount of the polyplexes was maintained by repeated UV
      irradiation, but the amount gradually decreased in the dark at 37 degrees C due
      to dissociation of the polyplexes, synchronized with the neutralization of the
      cation form of malachite green. The photo-cation generatable copolymers designed
      here can undergo photo-induced formation of the polyplexes with DNA and thermal
      polyplex dissociation, which may be used as a model for a novel photo-induced
      gene delivery system into cells.

PMID- 16305423
TI  - Chemo-enzymatic synthesis of a trisaccharide-linked peptide aimed at improved
      drug-delivery.
AB  - The glycosyltransferase enzyme LgtA, derived from the bacterial pathogen
      Neisseria meningitidis, was utilised in the chemo-enzymatic synthesis of a
      trisaccharide-linked endomorphin peptide drug candidate.

PMID- 16305424
TI  - Transdermal delivery of an analgesic agent using elastic liposomes: preparation,
      characterization and performance evaluation.
AB  - The aim of the present study was to prepare and characterize novel vesicular
      carrier elastic liposomes, of most commonly used non-steroidal anti-inflammatory
      agent diclofenac for its sustained and targeted delivery. Elastic liposomes of
      diclofenac were prepared and characterized in vitro and in vivo. The effect of
      different formulation variables like type of surfactant, concentration of
      surfactant and dose of drug on transdermal flux, amount of drug deposited into
      the skin, muscle and plasma concentration was investigated. The biological
      activity of optimized formulation was evaluated using carrageenan induced rat paw
      edema model and results were compared with commercial hydrogel formulation. The
      elastic liposomal formulations achieved muscle drug concentration between 2.2+/
      0.14 to 5.3+/-0.22 microg/g at 12 hr. The same dose of commercial hydrogel
      formulation produced drug levels between 0.41+/-0.07 to 1.1+/-0.09 microg/g in
      the muscle. Plasma concentration study showed regiospecificity of elastic
      liposomal formulation. The results of in vivo study revealed that incorporation
      of diclofenac in elastic liposomes increased its biological activity two fold as
      compared to commercial hydrogel formulation. The results of the present study
      demonstrated greater effectiveness of dermaly applied diclofenac elastic
      liposomal formulation in comparison to conventional delivery system. The
      optimized elastic liposomal formulation offers a promising means for the non
      invasive treatment of local pain and inflammation by topical application.

PMID- 16305425
TI  - Chitosan-based mucoadhesive microspheres of clarithromycin as a delivery system
      for antibiotic to stomach.
AB  - The objective of the present study was to develop chitosan-based mucoadhesive
      microspheres of clarithromycin to provide prolonged contact time for drug
      delivery of antibiotics to treat stomach ulcers. Microspheres based mucoadhesive
      formulation were extensively evaluated and characterized for in vitro performance
      followed by investigation of in vivo pharmacokinetics in rats. Microspheres were
      prepared by emulsification technique using glutaraldehyde as a crosslinking
      agent. Formulation conditions were optimized for percent drug entrapment and
      mucoadhesion, by varying different formulation and process parameters like drug
      to polymer ratio, concentration of crosslinking agent and time of crosslinking.
      Prepared microspheres were evaluated extensively for particle size, percent drug
      entrapment, swelling kinetics, in vitro mucoadhesion using rat stomach membrane
      and in vitro drug release studies. In vitro permeation studies across rat stomach
      membrane were carried out to determine diffusion parameters and drug retention in
      the stomach membrane of the formulation and the plain drug. Finally in vivo
      performance of microsphere formulation in comparison to plain drug was evaluated
      by pharmacokinetic studies in albino rats. Drug entrapment upto 74% was obtained.
      Swelling studies indicated that with an increase in cross-linking, the swelling
      ability decreased. The in vitro drug release and in vitro mucoadhesion studies
      showed a dependence on the extent of cross-linking and concentration of chitosan.
      Extent of cross-linking exhibited an inverse relation to drug release rate as
      well as mucoadhesion, whereas polymer concentration exhibited an inverse
      correlation with drug release while linear relationship with mucoadhesion (up to
      86%). In vitro permeation studies across stomach tissue showed higher
      accumulation of drug in the stomach tissue with microspheres formulation as
      compared to that of free drug. This is evident from higher value of K (partition
      coefficient) and Qm/Csf values for microspheres (68.34 and 106.42X10(3),
      respectively) as compared to that of free drug (1.86 and 173.00, respectively).
      These findings when analyzed showed an increase in the bioavailability of
      clarithromycin from microsphere formulation as compared to plain drug suspension
      in vivo, with AUC 0-->alpha being 91.7 (microg h/ml)and 24.9 (microg h/ml)
      respectively. Results of the study demonstrated good mucoadhesion of the
      microspheres with the stomach mucosa as well as higher accumulation of drug in
      the stomach membrane. Microspheres also exhibited sustained release of drug. Thus
      chitosan microspheres appear, technically, promising mucoadhesive drug delivery
      systems for delivering clarithromycin to treat stomach ulcers.

PMID- 16305426
TI  - Folate-linked lipid-based nanoparticle for targeted gene delivery.
AB  - Cancer gene therapy has been intensively developed using non-viral vectors, among
      which cationic liposomes and nanoparticles are the most thoroughly investigated.
      For targeted delivery to tumors, vitamin folic acid has been utilized for folate
      receptor (FR)-mediated drug delivery, since FR is frequently overexpressed on
      many types of human tumors. Liposomes conjugated to folate ligand have been used
      as carriers of chemotherapeutic agents and DNA to receptor-bearing tumor cells in
      vitro. As an alternative treatment for prostate cancer, suicide gene therapy by
      local injection using an adenoviral vector has been reported, but not that using
      non-viral vectors. The folate-linked, lipid-based nanoparticles which we
      developed could deliver genes extensively to FR-negative LNCaP and PC-3 cells, as
      well as FR-positive KB and Hela cells. In this review, we outline folate-linked
      liposomes and nanoparticles, and show the effectiveness of folate-linked, lipid
      based nanoparticles as a vector for DNA transfection and for suicide gene
      therapy, to treat human nasopharyngeal and prostate tumors.

PMID- 16305427
TI  - Carbon nanotubes: on the road to deliver.
AB  - Over the last few years, considerable advances have been made in the field of
      nanotechnology. The advent of carbon nanotube functionalization has paved the way
      for their potential application as a delivery system of diverse molecules such as
      peptides, proteins, plasmid DNA, and synthetic oligodeoxynucleotides. This opens
      new therapeutic and preventive opportunities to combat diseases. The scope of
      this review is to summarize our recent work in this rapidly growing field.

PMID- 16305428
TI  - Therapeutic chelators for the twenty first century: new treatments for iron and
      copper mediated inflammatory and neurological disorders.
AB  - Superoxide, hydrogen peroxide, hydroxyl radicals and peroxynitrite are
      collectively termed reactive oxygen and nitrogen species (RONS). They have been
      ascribed an important role in oxidative stress contributing to the progression of
      inflammatory diseases. RONS generating systems include the inflammatory response,
      enzymatic pathways and as side products of catabolism. Protective enzymes exist
      for the regulation of RONS such as superoxide dismutase, catalase and glutathione
      peroxidase. Furthermore, vitamins play a secondary role in deactivating RONS. The
      redox active metal ions such as ferrous and cuprous ions are released from the
      storage proteins ferritin and caeruloplasmin by RONS. Redox active metal ions
      further activate/generate RONS and thus perpetuate their damaging effects. Here
      we report recent therapies that focus on intervening in the roles of metal ions
      in oxidative stress. These include: i) chelators which complex labile metal ions
      to form antioxidant enzyme mimetics, ii) site-specific RONS scavengers, where
      dual functionality co-localizes the scavenger and chelation centre to direct
      scavenging, and iii) redox silencing, metal complexation with concomitant
      stabilization of the metal ion in the oxidized form to prevent further activation
      of RONS. The rationale for this new therapeutic approach and recent advances will
      be presented in this review.

PMID- 16305429
TI  - Erythromycin ethosomal systems: physicochemical characterization and enhanced
      antibacterial activity.
AB  - The rationale behind this work was that a permeation enhancing carrier could
      facilitate the transport of antibacterial molecules through the two biological
      barriers: stratum corneum of the skin and bacterial membrane/cell wall. To this
      end, erythromycin ethosomes (EE) were designed and characterized, and their
      antibacterial efficiency was evaluated in vitro and in vivo. TEM, CLSM, DLS, DSC
      and ultracentrifugation tests indicate that EE are small unilamellar soft
      vesicles encapsulating 78.6% erythromycin. The compositions were stable for at
      least one year at room temperature. In live/dead viability/cytotoxicity tests, EE
      systems were nontoxic to cultured 3T3 dermal fibroblasts. Susceptibility studies
      conducted on three bacterial strains (B. subtilis ATCC 6633, S. aureus ATCC 29213
      and S. aureus clinically resistant to erythromycin) showed significantly larger
      inhibition zones for EE as compared to erythromycin in hydroethanolic solutions.
      Moreover, EE reduced erythromycin MIC as compared to control solution: from 2.5
      to 1.25 microg/ml for S. aureus ATCC 29213 and from 12.5 to 5.0 microg/ml for
      clinically isolated resistant S. aureus strain. Ethosomal erythromycin applied to
      the skin of ICR mice inoculated with 10(7)cfu S. aurues ATCC 29213 resulted in
      complete inhibition of infection. On the contrary, when hydroethanolic solution
      of erythromycin was applied, deep dermal and subcutaneous abscesses developed
      within five days after challenge. On day seven, a similar number of S. aureus
      colonies (1.06x10(7) vs. 0.90x10(7) cfu/g tissue) were isolated from the
      untreated wounds or treated with hydroethanolic erythromycin. For these animals,
      histopathological examination showed necrosis, destroyed skin structures and
      dense infiltrates of neutrophils and macrophages. These findings show that
      ethosomes are efficient carriers for erythromycin delivery to bacteria localized
      within the deep skin strata for eradication of staphylococcal infections.

PMID- 16305430
TI  - Gastrointestinal absorption of heparin by lipidization or coadministration with
      penetration enhancers.
AB  - A review with 93 references. Heparins are high molecular weight, hydrophilic
      polyanions, which are unstable under acidic conditions; and therefore they
      exhibit poor oral bioavailability. Consequently they must be administered via the
      parenteral route which is expensive, inconvenient, and limits use by outpatients.
      The development of an oral form of heparin is warranted. This review examined the
      literature, mostly published between January 2000 and January 2005, pertaining to
      the gastrointestinal absorption of heparin by lipidization or coadministration
      with penetration enhancers. A lipidization strategy that was examined involved
      conjugation of low molecular weight heparin with deoxycholic acid. The majority
      of studies examined the ability of different formulations, typically utilizing
      penetration enhancers, to improve heparin bioavailability. The penetration
      enhancers used included fatty acids, Labrasol, Gelucire 44/14, polycationic
      lipophilic-core dendrons, saponins, mono-N-carboxymethyl chitosan, Carbopol 934P,
      a combination of thiolated polycarbophil and glutathione, polymeric
      nanoparticles, polymeric microparticles, sodium N-[8-(2-hydroxybenzoyl)
      amino]caprylate (SNAC), and sodium N-[10-(2-hydroxybenzoyl)amino]decanoate
      (SNAD). The variety of models used and doses of heparin/penetration enhancers
      applied, however, made it difficult to compare the results between studies.
      Nevertheless, all of the reviewed drug delivery systems showed therapeutic value
      and confirmation of the promising results obtained from animal studies, by
      progression to clinical trials, is necessary. Overall, progress has been made in
      the quest for an oral heparin formulation.

PMID- 16305431
TI  - Effects of glycerides on the intestinal absorption of cyclosporine a using the in
      situ mesenteric vein cannulated rat model.
AB  - The purpose of this study was to evaluate and compare the effect of glycerides
      with different fatty acid distributions (e.g. Arlacel 186, Capmul GMO and Captex
      350) on Cyclosporine absorption in rat ileum segment using the modified single
      pass intestinal perfusion with mesenteric vein cannulation. Drug concentration in
      the perfusate and blood plasma was analyzed by HPLC; and permeability
      coefficients were calculated from drug appearance in blood (P(blood)) and
      disappearance from perfusate (P(lumen)). Particle size was measured using Malvern
      Zetasaizer 1000HSA. Rheologic properties were measured using Brookfield
      viscometer. The results show that the average particle sizes after dilution (100
      folds) of formulae containing Arlacel 186, Capmul GMO and Captex 350 and
      containing 0.8 mM CsA were 260+/-35.8, 130+/-11.4 and 37.5+/-6.0 nm,
      respectively. The polydispersity index was 0.6, 0.7 and 0.108 for formulations
      with Arlacel 186, Capmul GMO and Captex 350, respectively. CsA permeability
      coefficients (P(blood)) calculated from drug appearance in the blood in presence
      of Arlacel 186, Capmul GMO and Captex 350 were 0.3x10(-6), 1.0x10(-6) and 1.7x10(
      6) cm2/sec, respectively. Phenol red was used as a water marker to determine net
      water absorption and secretion. Its constant concentration suggested that
      formulation did not alter intestinal water flux. From the results we can conclude
      that degree of glyceride esterification has a potential impact on the average
      particle size distribution and polydispersity of the formed micelles on dilution,
      which on turn contribute to the interaction between membrane and drug.

PMID- 16305432
TI  - Lipid-based nanosystems and complexes in experimental and clinical therapeutics.

PMID- 16305433
TI  - Engineering of nanoemulsions for drug delivery.
AB  - Nanoemulsions, usually spherical, are a group of dispersed particles used for
      pharmaceutical and biomedical aids and vehicles that show great promise for the
      future of cosmetics, diagnostics, drug therapies and biotechnologies. They exist
      in a wide variety of forms that are dictated by the particle components.
      Nanoemulsions are generally considered to be in the size range of less than and
      around 100 nm in diameter. The particles can exist as water-in-oil and oil-in
      water forms, where the core of the particle is either water or oil, respectively.
      More complex variations also exist but these are often larger. The longer-term
      properties of the particle are dependent on the composition of the adsorbed
      material lying at the dispersed droplet interface with the dispersion medium.
      This has an impact on the partitioning and extraction of droplet contents.
      Thermodynamically stable particles are characterized by having a very low surface
      tension and this produces a very large surface area. Nanoemulsions can also
      include small meta-stable very small-scale emulsions; here the surface properties
      and chemistry can strongly influence behaviour. Processing, storage and
      formulation composition can also have an impact on the longevity of a
      pharmaceutical preparation. Some revolutionary new nanoemulsion droplets based on
      fluorinated compounds are finding a number of widespread biomedical roles and
      applications. Developments in nanoemulsion technology are likely to lead to a
      much greater use of this medium in future pharmaceuticals.

PMID- 16305434
TI  - Targeted drug delivery to macrophages in parasitic infections.
AB  - Successful homing of drugs to the desired biological compartment of the host
      usually depends on the intrinsic properties of the drug molecules. However, it
      can always be manipulated by appropriate designing of the carrier/delivery
      system, as little can be done to influence the target and its surroundings.
      Various carrier systems have emerged to deliver drugs to macrophages, albeit the
      efficacy, reliability and selectivity of these carriers are still in question. To
      date, the most extensively studied carriers are liposomes and microspheres. In
      fact, physicochemical properties of these carriers can alter their efficacy and
      specificity to a great extent. These properties include hydrophilicity, surface
      charge, composition, concentration, and presence of various target specific
      ligands on their surface. Incidentally, the particulate nature of these vehicles
      may facilitate passive homing of the entrapped drug molecules to the macrophages,
      which may harbour many of the important pathogens in their intracellular
      compartments, such as Mycobacterium sps, Leishmania and dengue virus etc.,
      belonging to three different major classes of microbes. Moreover, macrophages
      upon interaction with particulate drug delivery vehicles may act as secondary
      drug depot, thus helping in localized delivery of the drug at the infected site.
      In the present article, a comprehensive review of literature is presented on the
      suitability of some lipid-based and polymeric materials as vehicles in delivery
      of drugs to macrophages in parasitic infections.

PMID- 16305435
TI  - Lipid-core micelles for targeted drug delivery.
AB  - Micelles, self-assembling nanosized colloidal particles with a hydrophobic core
      and hydrophilic shell are currently successfully used for the solubilization of
      various poorly soluble pharmaceuticals and demonstrate a series of attractive
      properties as drug carriers. Polymeric micelles, i.e. micelles formed by
      amphiphilic block co-polymers possess high stability both in vitro and in vivo
      and good biocompatibility. Among those micelles, lipid-core micelles, i.e.
      micelles formed by conjugates of soluble copolymers with lipids (such as
      polyethylene glycol-phosphatidyl ethanolamine conjugate, PEG-PE) are of special
      interest. These micelles can effectively solubilize a broad variety of poorly
      soluble drugs (anticancer drugs in particular) and diagnostic agents. Drug-loaded
      lipid-core micelles can spontaneously target body areas with compromised
      vasculature (tumors, infarcts) via the enhanced permeability and retention (EPR)
      effect. Lipid-core mixed micelles containing certain specific components (such as
      positively charged lipids) are capable of escaping endosomes delivering
      incorporated drugs directly into the cell cytoplasm. Various specific targeting
      ligand molecules (such as antibodies) can be attached to the surface of the lipid
      core micelles and bring drug-loaded micelles to and into target cells. Lipid-core
      micelles carrying various reporter (contrast) groups may become the imaging
      agents of choice in different imaging modalities.

PMID- 16305436
TI  - Phospholipid nanosomes.
AB  - Phospholipid nanosomes are small, uniform liposomes manufactured utilizing
      supercritical fluid technologies. Supercritical fluids are first used to solvate
      phospholipid raw materials, and then decompressed to form phospholipid nanosomes
      that can encapsulate hydrophilic molecules such as proteins and nucleic acids.
      Hydrophobic therapeutics are co-solvated with phospholipid raw materials in
      supercritical fluids that, when decompressed, form phospholipid nanosomes
      encapsulating these drugs in their lipid bilayers. Mathematical modeling and semi
      empirical experiments indicate that the size and character of phospholipid
      nanosomes depend on the several process parameters and material properties
      including the size and design of decompression nozzle, bubble size, pressure and
      the rate of decompression, interfacial forces, charge distribution and the nature
      of compound being encapsulated. Examples are presented for the encapsulation of a
      protein and hydrophobic drugs. In vitro and in vivo data on breast cancer cells
      and xenografts in nude mice indicate that paclitaxel nanosomes are less toxic and
      much more effective than paclitaxel in Cremophor EL (Taxol). Camptothecin
      nanosomes demonstrate that the normally very water-insoluble camptothecin can be
      formulated in a biocompatible aqueous medium while retaining in vivo efficacy
      against lymphoma xenografts in nude mice. In vitro data for betulinic acid
      nanosomes demonstrate enhanced efficacy against HIV-1 (EC50 of 1.01 microg/ml
      versus 6.72 microg/ml for neat betulinic acid). Phospholipid nanosomes may find
      utility in the enhanced delivery of hydrophilic drugs such as recombinant
      proteins and nucleic acid as well as hydrophobic anticancer and anti-HIV drugs.

PMID- 16305437
TI  - The formulation of lipid-based nanotechnologies for the delivery of fixed dose
      anticancer drug combinations.
AB  - The introduction of combination chemotherapeutic regimens for the treatment of
      childhood leukaemia in the 1960s provided the proof-of-principle that cytotoxic
      drugs were capable of curing cancer. However, in the four decades since this
      discovery, the majority of cancers still cannot be cured by chemotherapy.
      Clinical evidence supports the hypothesis of Goldie and Coldman that treating
      cancers with all the available effective agents simultaneously provides the
      greatest chance of eliciting a cure. Unfortunately, for traditional cytotoxic
      agents with narrow therapeutic indices, life-threatening toxicity precludes
      combination chemotherapy regimens employing multiple agents. This review
      discusses the concept of fixed dose combination chemotherapy with emphasis on
      capturing therapeutic efficacy described as synergistic as a basis for improving
      the effectiveness of combination chemotherapy. The use of lipid-based
      nanotechnologies, focusing on liposomes, as an enabling technology to facilitate
      the delivery of cytotoxic agents to the tumour site at concentrations and/or drug
      ratios judged to be synergistic will be discussed. It is envisaged that the
      development of this model system will be supported by cell-based screening
      technologies, pharmacokinetic and pharmacodynamic parameters and mathematical
      models describing therapeutic drug:drug interactions (the Median Effect Principle
      of Chou and Talalay). Experiments using preclinical models are presented to
      support the benefits of drug delivery systems as a foundation for fixed dose
      anticancer drug combinations. The ultimate goal of this research is to prepare a
      'single vial' fixed dose combination product that encompasses both traditional
      cytotoxic agents and new molecularly targeted modalities with optimum therapeutic
      effects and acceptable toxicity.

PMID- 16305438
TI  - Triggered activation and release of liposomal prodrugs and drugs in cancer tissue
      by secretory phospholipase A2.
AB  - The selectivity of anticancer drugs in targeting the tumour tissue presents a
      major problem in cancer treatment. In this article we review a new generation of
      smart liposomal nanocarriers that can be used for enhanced anticancer drug and
      prodrug delivery to tumours. The liposomes are engineered to be particularly
      degradable to secretory phospholipase A2 (sPLA2), which is a lipid hydrolyzing
      enzyme that is significantly upregulated in the extracellular microenvironment of
      cancer tumours. Thus, when the long circulatory liposomal nanocarriers
      extravasate and accumulate in the interstitial tumour space, sPLA2 will act as an
      active trigger resulting in the release of cytotoxic drugs in close vicinity of
      the target cancer cells. The sPLA2 generated lysolipid and fatty acid hydrolysis
      products will furthermore be locally released and function as membrane
      permeability promoters facilitating the intracellular drug uptake. In addition,
      the liposomal membrane can be composed of a novel class of prodrug lipids that
      can be converted selectively to active anticancer agents by sPLA2 in the tumour.
      The integrated drug discovery and delivery technology offers a promising way to
      rationally design novel tumour activated liposomal nanocarriers for better cancer
      treatment.

PMID- 16305439
TI  - Liposomal targeting of angiogenic vasculature.
AB  - Active targeting of angiogenic vasculature represents a promising therapeutic
      strategy to fight a variety of diseases. In particular, attention has been
      focused on inhibition of tumor growth. In this review, the recent progress in
      targeting liposomes to angiogenic endothelial cells is discussed.

PMID- 16305440
TI  - Ligand-targeted liposomes for cancer treatment.
AB  - Selective targeting of ligand-targeted liposomes containing anticancer drugs or
      therapeutic genes to cell surface receptors expressed on cancer cells is a
      recognized strategy for improving the therapeutic effectiveness of conventional
      chemotherapeutics or gene therapeutics. Some recent advances in the field of
      ligand-targeted liposomes for the treatment of cancer are summarized including:
      selection criteria for the receptors to be targeted, choice of targeting ligands
      and choice of encapsulated therapeutics. Targeting of liposomes to solid tumors,
      versus angiogenic endothelial cells versus vascular targets is discussed. Ligand
      targeted liposomes have shown considerable promise in preclinical xenograft
      models and are poised for clinical development.

PMID- 16305441
TI  - Lipid-based self-adjuvanting vaccines.
AB  - Lipopeptides incorporating epitopes for CD4+ T cells and either CD8+ T cells or B
      cells have proven to be immunogenic in animal models and in humans and are well
      tolerated in these species. This form of vaccine candidate has great benefits
      over competing technology in terms of providing a totally synthetic and pure
      product that is effective when administered in the absence of any adjuvant, and
      is immunogenic when delivered by a variety of routes, including application to
      mucosal surfaces. The immune response can be focused on critical epitopes of the
      pathogen or tumour antigen to provide clearing immunity, and responses can also
      be invoked that modulate hormone activity. This review will cover examples of
      lipopeptides of different design and their efficacy in different systems as well
      as challenges for the future. Our recent understanding of how the lipid component
      confers the "self-adjuvanting" property on these immunogens by targeting the cell
      at the heart of immune response induction, the dendritic cell, will also be
      discussed.

PMID- 16305442
TI  - Adjuvant and antigen delivery properties of virosomes.
AB  - Dramatic developments in vaccinology and immunology over the last decade have led
      to the identification of novel antigens, adjuvants and delivery systems, and
      combinations thereof, that may prove to be highly efficacious vaccines. Despite
      this explosion in technological developments, in reality, very few novel vaccines
      for human use have reached the market. Liposomes are one of the most intensively
      studied areas of vaccine and delivery system research. Several intrinsic features
      of liposomes lend themselves to their use in vaccines, particularly in terms of
      safety, versatility and adjuvant properties. Modifications to liposomal
      structures in terms of additional adjuvants are also playing a role in potential
      medical applications. The most significant progress to date has been made with
      virosomes, a novel antigen delivery system that incorporates the haemagglutinin
      from influenza virus into liposomes and can induce both humoral- and cell
      mediated immunity to antigens. This review discusses the presentation and
      processing of antigens delivered by virosomes, in light of both licensed vaccines
      and potential vaccine candidates.

PMID- 16305443
TI  - Lipid-protamine-DNA-mediated antigen delivery.
AB  - The development of novel 'new generation' vaccine systems that is based on
      proteins, peptides or DNA is of great current interest. However, due to the lower
      efficiencies of these new generation vaccines, they are seldomly used alone.
      Rather, their formulations often contain adjuvants, either to enhance the immune
      responses or to reduce dosing. The present chapter will provide a brief overview
      of the recent advances in peptide-based cancer vaccine adjuvants, focusing mainly
      on Liposome-Protamine-DNA (LPD) nanoparticle-mediated antigen delivery.

PMID- 16305444
TI  - Archaeosome immunostimulatory vaccine delivery system.
AB  - Archaeosomes are liposomes made from the polar ether lipids of Archaea. These
      lipids are unique and distinct in structure from the ester lipids found in
      Eukarya and Bacteria. The regularly branched and usually fully saturated
      isopranoid chains of archaeal polar lipids are attached via ether bonds to the sn
      2,3 carbons of the glycerol backbone(s). The polar head groups are usually the
      same as those encountered in the ester lipids from the other two domains, except
      that phosphatidylcholine is rarely present. These lipid structures provide
      formulary advantages, and contribute to the excellent physico-chemical stability
      of the archaeosomes and their efficacy as self-adjuvanting vaccine delivery
      vesicles. The uptake of archaeosomes by phagocytic cells is several folds greater
      than that of liposomes made from ester lipids. In addition, archaeosomes enhance
      the recruitment and activation of professional antigen presenting cells in vivo,
      and deliver the antigen to both MHC class I and II pathways for antigen
      presentation, without eliciting overt inflammatory responses. In murine models,
      systemic administration of archaeosomes containing encapsulated antigen(s)
      elicits strong and sustained antigen-specific antibody responses which are
      comparable, in some formulations, to those obtained with Freund's adjuvant.
      Additionally, archaeosomes promote robust antigen-specific cell-mediated
      immunity, including CD8+ CTL responses. The immune responses induced by
      archaeosomes are sustained over long periods and exhibit strong memory responses.
      More importantly, immunization of mice with archaeosome-based vaccines induces
      robust protective immunity against intracellular pathogens, and prophylactic and
      therapeutic efficacies against the development of experimental cancers. Extensive
      murine model studies suggest that archaeosomes are safe.

PMID- 16305445
TI  - Lipid carriers for gene therapy.
AB  - A wide variety of lipid molecules used as gene carriers has been reported and
      compared over the last twenty years. This review highlights a few examples of
      mechanistic analysis applied to the study of lipid carriers. The modular nature
      of the lipid structure offers itself up to a controlled, systematic analysis. Key
      to exploring structural variants is the understanding of the role each component
      and module plays in the formation of the lipoplex structure itself and their
      roles in the transfection pathway. Firstly, the lipid carrier must be able to
      package, and release into the cell its nucleic acid cargo. Uptake of lipoplexes
      into cells involves endocytic processes that lead inevitably to
      endosomal/liposomal degradation of the nucleic acid contents, unless lipid
      structures and designs are optimised to facilitate their release into the
      cytoplasm. Testing of possible endosomal escape mechanisms has led to improved
      lipid designs. For example, it was predicted that mixing of cationic lipids with
      shorter alkyl tails (<C18) from liposomes with the endosomal bilayer during the
      transfection process within the endosome should promote membrane fluidity,
      enhancing plasmid release and transfection efficiency. This hypothesis has been
      borne out numerous times. "Smart" molecules that respond to cellular cues such as
      endosomal pH have now been developed that appear to offer exciting opportunities
      for the future role of lipoplexes in clinical applications of gene therapy. The
      variability of cultured cell and model biological systems remains a challenge in
      designing improved lipids of general utility.

PMID- 16305446
TI  - Toxicogenomics of cationic lipid-based vectors for gene therapy: impact of
      microarray technology.
AB  - Implementation of the high-throughput microarray gene expression profiling
      technology towards "toxicogenomics" has advanced identification process for safer
      drugs in the century of 'omics' technology. Applying such technology, in fact, to
      identify mechanisms for cellular toxicity can provide a means to clarify safety
      liabilities early in the drug discovery and developments process. The underlying
      principle in gene therapy is primarily targeting a specific gene (e.g., for
      silencing). Hence, massive efforts have been devoted to validate the gene-based
      therapeutics, regardless of toxicogenomics potential of delivery systems. Of the
      gene delivery systems, viral and non-viral vectors, as two main paradigms, have
      so far been widely used for delivering of the genome-based therapeutics such as
      oligonucleotide, small interfering RNA and DNA. However, the use of viral vectors
      was narrowed due to the safety concerns. Non-viral vectors were utilized as safer
      alternatives for gene delivery in vitro and ex-vivo; though their success for in
      vivo gene therapy has been limited due to low efficiency and safety issues.
      Fundamental principle for gene therapy is to deliver gene-based therapeutics into
      target cells for specific gene targeting ideally with minimal cellular toxicity.
      Until now, few works have been conducted about geno-compatibility of delivery
      systems itself, including cationic lipid-based nanosystems. Inadvertent
      toxicogenomic impact of gene delivery systems (e.g., cationic lipids) may
      intrinsically affect the outcome of gene therapy, where often only a single
      desired genetic change is sought. Further, there exists a possibility that gene
      changes induced by the lipid delivery system itself could exacerbate, attenuate
      or even mask the desired effects of the gene-based therapeutics. This review will
      focus on toxicogenomics impact of the cationic lipid-based formulations for gene
      therapy.

PMID- 16305447
TI  - Complement activation-related pseudoallergy caused by amphiphilic drug carriers:
      the role of lipoproteins.
AB  - Self-assembling amphiphilic lipids or polymers have been successfully used in
      pharmacotherapy as drug solvents or carriers, improving the bioavailability of
      water-insoluble drugs. This review focuses on an unusual hypersensitivity
      reaction (HSR) caused by a micellar (Cremophor EL, CrEL) and a monomeric block
      copolymer (poloxamer 188) representative of these systems. The HSRs, also
      referred to as anaphylactoid or pseudoallergic, are thought to arise as a
      consequence of complement (C) activation in blood. However, considering that C
      activation involves the deposition of multiple C and other (immune) proteins on
      the activator surface, the mechanism by which small, 8-25 nm CrEL micelles or
      individual poloxamer 188 molecules activate C is not straightforward.
      Observations on enlarged lipoproteins and de novo formation of abnormally large
      lipoprotein-like structures in plasma exposed to CrEL or poloxamer 188 raise the
      possibility that lipoprotein transformation might play a crucial role in C
      activation by these amphiphilic emulsifiers. Lipoproteins, furthermore, can also
      provide a negative feedback control on C activation, as suggested by the
      inhibition of poloxamer 188-induced C activation in the presence of excess
      exogenous lipoproteins, and the attenuation of liposome-induced and C activation
      related hypotension in pigs by precoating the vesicles with lipoproteins. Thus,
      lipoproteins may be essential in the induction, and they may also play a complex
      modulatory role in C activation-related pseudoallergy caused amphiphilic drug
      solvents and carriers.

PMID- 16305448
TI  - Analgesia in PACU: intravenous opioids.
AB  - Critically ill patients, particularly those under mechanical ventilation, require
      analgo-sedation to control noxious stimuli and enhance comfort. Despite their
      harmful side effects, such as respiratory depression, physical dependence and
      difficult arousal, opioids are effective in providing a good level of analgesia
      and comfort. Traditional opioids (morphine and fentanyl) have been shown
      effective in providing analgesia; however, the respiratory adverse effects and
      their pharmacokinetics, with an high risk of accumulation, limits their use,
      especially for a long-term sedation. In the last decade, new synthetic opioids
      with limited side effects and favourable pharmacokinetics profile, such as
      Sufentanil and Remifentanil, have been investigated to evaluate their efficacy in
      mitigating pain and enhancing comfort in critically ill patients.

PMID- 16305449
TI  - Sedation and analgesia in Post-Anesthesia Intensive Care Unit.

PMID- 16305450
TI  - Sedation in PACU: indications, monitoring, complications.
AB  - The aim of the present article is to review the indications, the monitoring and
      the complications of sedation in the post-anaesthesia care unit (PACU). In this
      setting, sedation is often an unwanted side effect of anaesthetic drugs that
      delay discharge, however it could be specifically indicated. Such indications
      include postoperative anxiety and agitation, airway management and mechanical
      ventilation, protection against myocardial ischaemia and intracranial
      hypertension control. Whenever sedation is used, an appropriate monitoring is
      useful to achieve an adequate level for the specific indication. Methods for
      sedation monitoring in PACU may be subjective (clinical scales) or objective
      (lower oesophageal sphincter contractility measurement, heart rate variability,
      evoked potentials and parameters derived from the electroencephalogram). The
      target score of the most common clinical scales has been reviewed according to
      the specific indication. An adequate monitoring is fundamental to avoid the
      complications of sedation including bradycardia, hypotension, prolonged
      mechanical ventilation and increased risk of respiratory tract infection as
      pointed out by many recent data. Therefore, sedation should be used carefully and
      with an adequate monitoring in post-operative patients not to affect negatively
      morbidity and mortality.

PMID- 16305451
TI  - Sedation in PACU: the role of propofol.
AB  - In critically ill patients, adequate sedation increases comfort, minimizes stress
      response and facilitates diagnostic and therapeutic procedures. Propofol (2-, 6
      diisopropylphenol) is an intravenous sedative-hypnotic agent popular for sedation
      in the Intensive Care Unit. The favorable propofol pharmacokinetic, characterized
      by a three compartment linear model, allows rapid onset and short duration of
      action. The emergence time from sedation with propofol varies with the depth and
      the duration of sedation and the patient's bodyweight. Propofol causes
      hypotension, particularly in volume depleted patients, decreases cerebral oxygen
      consumption, reduces intracranial pressure and has potent anti-convulsant
      properties. It is a potent antioxidant, has anti-inflammatory properties and is a
      bronchodilator. As a consequence of these properties, propofol is being
      increasingly used in the management of traumatic head injury, status epilepticus,
      delirium tremens, status asthmaticus and in septic patients. Prolonged use (>48
      h) of high doses of propofol (>66 mcg/Kg/min) has been associated with lactic
      acidosis, bradycardia, and lipidemia in pediatric patients. A rare complication
      firstly reported in pediatrics patients and also observed in adults is known as
      "propofol syndrome" characterized by myocardial failure, metabolic acidosis and
      rhabdomiolysis. Hyperkalemia and renal failure have also been associated with
      this syndrome. Hypertriglyceridemia and pancreatitis are uncommon complications.
      A large number of trials have compared the use of propofol with midazolam.
      Sedation with propofol is associated with adequate sedation in ICU patients,
      shorter weaning time and earlier tracheal extubation compared to midazolam, but
      not before ICU discharge.

PMID- 16305452
TI  - Sedation in PACU: the role of benzodiazepines.
AB  - Many patients in the ICU receive mechanical ventilation and require sedative
      medications. Anxiolysis, hypnosis, and amnesia can be considered the primary
      objects of sedative therapy. Intravenous benzodiazepines are the drugs most
      commonly used for sedation in ICU. Proper choice and use of benzodiazepines is
      based on knowledge of the pharmacology and is an essential component of caring
      for patients in the intensive care unit. Three benzodiazepines--Diazepam,
      Lorazepam and Midazolam--are currently available for parenteral use in the ICU.
      Onset and duration of action are determined by their lipid solubility.
      Respiratory depression and hypotension are dose-dependent. Midazolam is generally
      preferred to other benzodiazepines in most ICU. It has the shortest half-life of
      the benzodiazepines, does not have active metabolites, is water soluble and can
      be administered by continuous infusion. Despite the relatively short half-life of
      Midazolam, extensive distribution can cause prolonged sedation. Recovery time is
      proportional to the infusion's duration. Lorazepam is lipid soluble and dissolved
      in a propylene glycol carrier, produces a delayed onset and prolonged duration of
      effect and is preferred for long-term sedation (>48 hours). Propylene glycol
      toxicity is possible with high-dose or prolonged infusions. Diazepam has become
      less used with the introduction of the shorter-acting and less irritating
      benzodiazepine. The recent literature focuses on the differences between
      Midazolam and Propofol, the most used sedatives in ICU, their sequential use and
      combination. Relevant studies have been performed about propylene glycol
      toxicity.

PMID- 16305453
TI  - Alpha-2 agonists: can they modify the outcomes in the Postanesthesia Care Unit?
AB  - While most patients recover uneventfully from the effects of anesthesia and
      surgery, for a small percentage of patients the immediate postoperative period
      can be a period of significant physiological stress. Hence the goal for a Post
      Anesthesia Care Unit (PACU) is to provide a safe environment for a patient to
      recover, while avoiding the undesirable side effects of pain, nausea, vomiting
      and shivering, and to monitor for potentially life threatening hemodynamic and
      respiratory complications that may require admission into the intensive care unit
      (ICU). Anesthetic techniques in the operating room are extremely important as
      these may have significant bearing on the post-operative course. The type of
      surgery, the patients' co morbid conditions, anticipated extubation and recovery
      of the patient, as well as the sophistication of the PACU and the expertise of
      its staff, all influence the choice of anesthetic technique. These agents,
      however, may themselves contribute to some of the complications and unpleasant
      events encountered in the PACU. Therefore, evaluation of newer and safer agents,
      which promote a smoother PACU transition, are warranted. Alpha 2 agonists are
      increasingly being used as adjuvant therapeutic agents in the perioperative
      period because of their ability to block the sympathetic stress response,
      complete with their anesthetic and analgesic sparing properties, lack of
      respiratory depression and low and predictable side effect profile.

PMID- 16305454
TI  - Analgesia in PACU: indications, monitoring, complications.
AB  - The correct treatment of postoperative pain, in the early period immediately
      following surgery, is founded on the following four principles: 1-correct
      diagnosis of the source and magnitude of nociception; 2-understanding of the
      relationship of ongoing nociception and other components of pain including
      anxiety, ethnocultural components, meaning, prior experience; 3-treatment by
      establishment and maintenance of drug level at active sites to achieve and
      maintain analgesia and anxiolysis as appropriate; 4-continued re-evaluation of
      the therapy and refinement of the approach. The PACU standard of cure requires a
      strict accordance between intra and postoperative analgesia. It requires
      "proactive preoperative plan" that includes: preoperative patient evaluation;
      discussion with a single patient on different treatment options; patient and
      family education; pre-emptive measures as indicated; intra-operative multimodal
      analgesia; a correct triage of analgesia, just after initial evaluation of vital
      parameters in PACU; re-evaluation of analgesia plan, if analgesia is inadequate;
      a new titration, intravenous or epidural way, in order to achieve a stable VAS <
      3; plan a new analgesia scheme or confirm a preoperative plan; control of adverse
      events, related to analgesia plan (gastric bleeding and/or bleeding of the
      surgical wound site, NSAIDs-induced renal damage, respiratory depression, delayed
      canalisation, nausea, vomiting, excessive sedation, difficulty in bladder
      emptying, itchiness); a transmission of analgesia plan to ward nurses; a control
      quality for verify at prefixed times patients satisfaction level, analgesia
      performed, adverse effects percent, analgesia related, plan variations percent.

PMID- 16305455
TI  - Opioids: other routes for use in recovery room.
AB  - Opioids remain the main pharmacological tools for pain control in the
      postoperative patient. Recent concerns about chronic use of non-steroidal anti
      inflammatory drugs have put extra pressure on health care workers to device and
      develop new medications and delivery methods to provide patients with appropriate
      pain relief after surgery. New technologies and better understanding of the
      pharmacology of the opioids administered by non-traditional ways will be reviewed
      in this manuscript. Understanding the anatomy of the nose cavity is important to
      use the inhaled way to deliver fentanyl, sufentanyl or butorphanol in surgical
      patients. High concentration and small volume are keys to good absorption and
      effect by nasal administration. Transdermal delivery of fentanyl has been used in
      chronic pain for some years. A new fentanyl self-administration method is in
      advanced trials for clinical use. It has a huge potential in giving good pain
      relief with lower side effects and more patient independence because of its
      reduced size and lack of tubing attached to it. Day surgery patients could be
      great candidates for this therapeutic alternative. Finally, oral transmucosal
      fentanyl is also in the market. Better suited to be used in controlling
      breakthrough pain in chronic settings, it has been so far marketed in the
      perioperative period. Side effects are a concern in its use for preoperative
      sedation in children. Large studies are now required for drugs approval and for
      new indications at regulatory agencies level. Good clinical judgment is more
      relevant now than ever before to avoid complications and new withdraw of old good
      medications inappropriately prescribed from the market place.

PMID- 16305456
TI  - Analgesia in PACU: nonsteroidal anti-inflammatory drugs.
AB  - Control and abolition of pain during and after surgical procedures is crucial
      point in the practice of anaesthesiology. In the last years the concept of
      multimodal analgesia (the use of different analgesic and techniques to relieve
      pain), has developed and non-steroidal anti-inflammatory drugs (NSAIDs) have a
      major role in it, because they have an opioid sparing effect. Moreover, they are
      very effective on somatic and breakthrough pain. NSAIDs can be divided
      functionally in four classes: salicylates, acetaminophen, non-specific inhibitors
      (i.e. ibuprofen, ketorolac, etc.) and cyclooxygenase2-inhibitors (coxibs). The
      target of action of these drugs is the different isozymes of the Prostaglandin
      G/H synthase, called Cyclooxygenases (COX). At least three different types of COX
      have been identified, which are probably organ specific. These isozymes play a
      crucial role in the developing of the inflammatory cascade, and in the genesis of
      various pain mediators released from tissue injury. Their most important side
      effects affect mainly gastrointestinal system, the kidney and the coagulation
      system. Less important are the effects on the liver and the immunologic system
      (asthma). The analgesic nephropathy and the coagulopathy must be taken into
      account in the surgical patient, for the possibility of increase perioperative
      morbidity. Very recently the newest class of coxibs, although they reduce g.i.
      bleeding and coagulopathy, have proved to increase the risk of cardiovascular
      accidents both in long term therapy than postoperatively in cardiac surgical
      patients. Many data are needed, but in patients at high risk of cardiac disease
      other NSAIDs should be considered.

PMID- 16305457
TI  - Ketamine: new indications for an old drug.
AB  - Ketamine is a non-competitive antagonist to the phencyclidine site of N-methyl-d
      aspartate (NMDA) receptor for glutamate, though its effects are mediated by
      interaction with many others receptors. It has been introduced in clinical use
      since 1960's but today it is not largely employed as a general anaesthetic for
      its undesired psychic effects (emergence reactions) occurring in approximately
      12% of patients. In the last decade, there has been a renewed interest in the use
      of subanaesthetic doses of ketamine for the treatment of acute and chronic pain.
      In the late 1990's, multiple prospective, randomised, controlled study has shown
      the efficacy of low dose of ketamine for postoperative pain relief, for analgesia
      during regional or local anaesthesia, and for opioid-sparing effect. At present,
      non-definitive conclusion can be drawn. More data are needed to define the
      possible long term effects and the clinical goal of ketamine use.

PMID- 16305458
TI  - Epidural analgesia in the Post-Anaesthesia Care Unit.
AB  - Epidural analgesia is widely used for postoperative pain in a variety of surgical
      operations and it is recognised to provide superior quality of analgesia when
      compared with systemic opioids. The combination of low doses of local
      anaesthetics and opioids appears to provide optimal analgesia with minimal motor
      blockade. However, side effects have been reported with epidural analgesia such
      as postoperative nausea and vomiting (PONV), respiratory depression and arterial
      hypotension. Although the incidence of these side effects is lower than those
      reported with the use of systemic opioids, they can contribute to a delay in
      discharging patients from PACU. Epidural analgesia is also associated with
      perioperative hypothermia. The incidence of cognitive dysfunction is not
      decreased by using postoperative epidural analgesia. Assessment of the quality of
      analgesia by using pain visual analogue score (VAS) at rest and with movements or
      on coughing remains the most preferred in PACU, although there are limitations
      with this measurement. Epidural failure due to technical failure or malposition
      of the catheter represents potential problems having direct consequence on the
      quality of analgesia provided. All epidural catheters have to be checked and the
      quality of analgesia assessed before patients are discharging from PACU to the
      surgical wards. With advances in pain pharmacology, multimodal interventions and
      adjuvants can be used safely with the intent of providing better analgesia and
      decreasing the side effects associated with one technique.

PMID- 16305459
TI  - Postoperative delirium.
AB  - Delirium is a global impairment of upper brain functions caused by an organic
      substrate. It is frequently observed in the postoperative period, particularly in
      elderly people. Vascular and orthopedic surgery and long-duration surgery are
      associated with a higher incidence of postoperative delirium. When it occurs,
      postoperative delirium makes patient management much more difficult, increases
      costs, and, above all, causes severe discomfort to the patient. Delirium is also
      associated with higher postoperative mortality and morbidity, and with delayed
      functional recovery, but it is still unclear whether worse prognosis is directly
      caused by delirium or results from the neurological damage of which delirium is
      simply a symptom. Drug therapy should be part of a complex approach to prevent
      and treat this complication. Neuroleptics like haloperidol and droperidol, and
      benzodiazepines are usually employed in order to control symptoms like agitation,
      restlessness, and altered perceptions. Atypical neuroleptics, like risperidone,
      have not yet been studied in postoperative delirium, although some case reports
      in which they were successfully used have been published. Physiostigmine is
      effective in delirium caused by anticholinergic syndrome; vitamins may be useful
      in alcoholics; melatonin use has been suggested in order to prevent and treat
      delirium by normalizing sleep-wake cycle alterations. Environmental interventions
      are often costless and may be very useful to prevent and treat postoperative
      delirium in patients at risk.

PMID- 16305460
TI  - Patient-controlled analgesia.
AB  - Using a portable infusion pump, intravenous opioid patient-controlled analgesia
      (PCA) permits a patient to self-deliver a small bolus of opioid to achieve prompt
      relief without over sedation. Use of PCA for pain management is increasing in
      hospitals, largely because it can provide equivalent or better analgesia than
      conventional nurse-administered opioid analgesia, and patients are more satisfied
      with its use. There is no decisive pharmacological or clinical argument for the
      choice of one opioid rather than another. Thus, morphine remains the most
      frequently used opioid in PCA. The adjunction of non-opioid drugs to morphine in
      the PCA reservoir is still very controversial. A new investigational PCA
      transdermal system using iontophoresis to deliver fentanyl seems to provide an
      adequate pain control with the advantages of needle-free, preprogrammed, self
      contained device. Whatever drug or device used, the overall success of the PCA
      technique relies mainly on the expert supervision of nurses or anesthesiologists
      in an Acute Pain Service. Indeed, PCA is effective and significant only on the
      condition that there is careful preoperative patient education and strict
      postoperative monitoring. In addition, preoperative patient selection allows to
      exclude patients with evidence of cognitive dysfunction or physical disabilities,
      making the use of the patient-controlled device impossible. Caution is required
      among patients with respiratory or renal insufficiency. In the future, the
      indispensable improvement in the management of postoperative pain should lead to
      a greater expansion of PCA. However, more pharmaco-economic evaluations will be
      needed on the cost-effectiveness issue.

PMID- 16305461
TI  - Reactive astrocytes as potential manipulation targets in novel cell replacement
      therapy of Parkinson's disease.
AB  - Parkinson' disease (PD) is a most common and debilitating degenerative disease
      resulted from massive loss of dopamine neurons in the substantia nigra pars
      compacta, which is characterized by severe motor symptoms of tremor,
      bradykinesia, rigidity and postural instability. Protection of nigral dopamine
      neurons from progressive degenerative death and cell replacement of novel
      dopamine neurons are hopeful strategies against PD in humans. The reactive
      astrocytes or functional activation of astrocytes abundantly occurred in brain
      insults including trauma, ischemia, and 6-OHDA or MPTP-treated PD animal models.
      Although they were traditionally assumed to impede neuronal regeneration by
      forming glial scars, growing evidence has indicated that reactive astrocytes do
      offer crucial benefits in functional recovery of brain injuries. The reactive
      astrocytes can produce various neurotrophic factors for neuron survival,
      synthesize extracellular substrates for axonal outgrowth and synaptogenesis, act
      as scavengers for free radical and excess glutamate, and promote neurogenesis of
      neural progenitor cells in the adult brains. We thereafter hypothesize that
      reactive astrocytes may also play important roles in the protection of nigral
      dopamine neurons or transplanted dopamine cells through their neurotrophic
      functions and active interaction with dopamine neurons or neural progenitor
      cells. Future approaches deserve to target on neurotrophic functions of reactive
      astrocytes in the basal ganglia and interventions to facilitate survival and
      axonal regeneration of dopamine neurons or differentiation of dopamine progenitor
      cells. Novel pharmaceutical and cell replacement strategies will hopefully be
      developed by potential manipulation of reactive astrocytes in the basal ganglia
      in prevention and treatment of Parkinson's disease.

PMID- 16305462
TI  - Targeted agents for the treatment of advanced renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is a highly treatment-resistant tumor type; however,
      advances in elucidating the molecular pathophysiology underlying RCC has led to
      the identification of promising targets for therapeutic intervention. In clear
      cell RCC, mutations to the von Hippel-Lindau (VHL) gene results in the up
      regulation of many proteins necessary for tumor growth and survival--such as
      vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)
      and platelet derived growth factor (PDGF), which are involved in tumor-initiated
      angiogenesis. Carbonic anhydrase IX and signaling via the epidermal growth factor
      receptor (EGFR) are involved in tumor cell proliferation and are also up
      regulated by mutation in the VHL gene. The intracellular messenger pathways
      phosphoinositide 3-kinase (PI3K) and Raf/MEK/ERK act as convergence points for
      positive growth signaling; the Raf/MEK/ERK pathway is also implicated in
      apoptosis. Several agents in development target VEGF (bevacizumab), the VEGF
      receptor (PTK787, SU11248, VEGF-trap, and BAY 43-9006), the PDGF receptor
      (SU11248 and BAY 43-9006), or the EGF receptor (gefitinib, cetuximab, ABX-EGF,
      and erlotinib). The intracellular Raf/MEK/ERK signaling cascade has been targeted
      at either the level of Raf (BAY 43-9006, ISIS 5132) or MEK (CI-1040, PD184352 and
      ARRY-142886), and PI3K signaling is disrupted by CCI-779. WX-G250 targets the
      G250 antigen, and PS-341 disrupts the 26S proteasome mediating the degradation of
      intracellular proteins. Given that multiple pathways contribute to tumor growth,
      anti-tumor activity may be increased by agents targeting multiple pathways, or by
      combining agents to allow horizontal or vertical inhibition of multiple pathways.

PMID- 16305463
TI  - Regulatory molecules and chelators used for the control of essential and toxic
      metals in health and disease: from molecular interactions to clinical effects and
      applications.

PMID- 16305464
TI  - Advances in iron overload therapies. prospects for effective use of deferiprone
      (L1), deferoxamine, the new experimental chelators ICL670, GT56-252, L1NA11 and
      their combinations.
AB  - Effective new therapies and mechanisms have been developed for the targeting and
      prevention of iron overload and toxicity in thalassaemia and idiopathic
      haemochromatosis patients. A new era in the development of chelating drugs began
      with the introduction of deferiprone or L1, which as a monotherapy or in
      combination with deferoxamine can be used universally for effective chelation
      treatments, rapid iron removal, maintenance of low iron stores and prevention of
      heart and other organ damage caused by iron overload. Several experimental iron
      chelators such as deferasirox (4-[3,5-bis (2-hydroxyphenyl)-1,2,4-triazol-1-yl]
      benzoic acid) or ICL670, deferitrin (4,5-dihydro-2- (2,4-dihydroxyphenyl)-4
      methylthiazole-4 (S)-carboxylic acid) or GT56-252, 1-allyl-2-methyl-3
      hydroxypyrid-4-one or L1NAll and starch deferoxamine polymers have reached
      different stages of clinical development. The lipophilic ICL670, which can only
      be administered once daily is generally ineffective in causing negative iron
      balance but is effective in reducing liver iron. It is suspected that it may
      increase iron absorption and the redistribution of iron from the liver to the
      heart and other organs. The experimental iron chelators do not appear to have
      significant advantages in efficacy and toxicity by comparison to deferiprone,
      deferoxamine or their combination. However, the prospect of combination therapies
      using deferiprone, deferoxamine and new chelators will provide new mechanisms of
      chelator interactions, which may lead to higher efficacy and lower toxicity by
      comparison to monotherapies. A major disadvantage of the experimental chelators
      is that even if they are approved for clinical use, they are unlikely to be as
      inexpensive as deferiprone and become available to the vast majority of
      thalassaemia patients, who live in developing countries.

PMID- 16305465
TI  - Structure/function overview of proteins involved in iron storage and transport.
AB  - Iron, the major trace element in the body, is an essential component of many
      proteins and enzymes. As low-molecular-weight iron is potentially toxic to cells,
      higher organisms express a number of proteins for the transport and storage of
      iron. We review our current understanding of the intestinal absorption of iron in
      the light of recently identified membrane proteins, namely the ferrric reductase,
      Dcytb, the two iron(II) transport proteins, DMT1 and ferroportin/Ireg1, and
      hephaestin, the membrane-bound homologue of the ferroxidase ceruloplasmin. Two
      types of mammalian transferrin receptor, TfR1 and TfR2, are now known to exist.
      The structure of TfR1 and its role in the process of receptor-mediated cellular
      uptake of iron are presented together with structural information on the iron
      storage protein ferritin. Mechanisms for the regulation of levels of TfR1 and
      ferritin, as well as other proteins involved in iron homeostasis, are discussed.
      Our current knowledge and understanding of the structure of members of the
      transferrin family of iron-binding proteins and the nature of the iron-binding
      centres in transferrins is presented, together with information on the processes
      of iron-uptake and iron-release by transferrin and a summary of the elements that
      have been found to bind to transferrins.

PMID- 16305466
TI  - Molecular factors and mechanisms affecting iron and other metal excretion or
      absorption in health and disease: the role of natural and synthetic chelators.
AB  - The maintenance of iron and other essential metal ion balance in humans is based
      on the presence of homeostatic mechanisms of regulatory absorption, storage, re
      utilisation and excretion. There are a number of factors and mechanisms that can
      affect the level of iron excretion or absorption and overall body iron stores.
      Net iron loss due to increased iron excretion by comparison to dietary iron
      absorption is considered as one of the causes of iron deficiency anaemia. Body
      iron loss greater than normal has been shown in many other conditions. These
      include the increase in urinary iron excretion observed in iron loaded patients,
      the substantial reduction in serum ferritin and liver iron of ex-thalassaemia
      patients several years following bone marrow transplantation and the increase in
      iron excretion in normal individuals following long term sport activities. There
      are differences in the metabolism, mode of action, interactions with the iron
      pools and routes of iron excretion, of the iron chelating drugs deferiprone (L1),
      deferoxamine and other experimental chelators such as ICL670 in iron-loaded
      patients. Naturally occurring chelators and some synthetic drugs are known to
      bind iron and affect iron absorption and excretion. The molecular characteristics
      of naturally occurring or synthetic chelators can influence other aspects of iron
      metabolism in addition to iron absorption or excretion. Similar mechanisms and
      factors can affect the metabolism of other essential metals. The understanding of
      the mechanisms involved in iron excretion and their overall effects on body iron
      levels can facilitate the design of new chelators and improved therapeutic
      protocols for the treatment of conditions of iron and other metal metabolic
      imbalance and toxicity.

PMID- 16305467
TI  - Molecular mechanisms of iron uptake by cells and the use of iron chelators for
      the treatment of cancer.
AB  - The field of iron (Fe) metabolism has been invigorated in the past 10 years with
      the discovery of a variety of new molecules involved in the homeostatic control
      of this critical nutrient. These proteins include the transferrin receptor 2,
      frataxin, hephaestin, hepcidin, hemojuvelin and others. Basic understanding of
      the metabolism of Fe in cells is vital in order to develop Fe chelators for the
      treatment of a variety of disease states. In addition, examination of the role of
      Fe in the regulation of cell cycle progression and angiogenesis has led to
      investigations of the use of novel Fe chelators as anti-proliferative agents.
      These studies have resulted in the identification of new ligands that show
      selective and potent anti-tumor activity in vitro and in vivo. Moreover, the
      ability of these chelators to inhibit growth is not only limited to the
      inhibition of DNA synthesis. In fact, there is a range of targets that are
      affected by Fe-depletion, such as molecules involved in cell cycle control,
      angiogenesis and metastasis suppression. These include hypoxia-inducible factor-1
      alpha (HIF-1 alpha), vascular endothelial growth factor-1 (VEGF1),
      p21(CIP1/WAF1), cyclin D1 and the protein product of the N-myc downstream
      regulated gene-1 (Ndrg1). As such, Fe chelators can now be designed to target
      molecules to induce specific effects, for instance, angiogenesis or metastasis
      suppression.

PMID- 16305468
TI  - Superoxide and nitric oxide in pathological conditions associated with iron
      overload: the effects of antioxidants and chelators.
AB  - Free radicals are a one of damaging factors in diseases associated with iron
      overload. This review considers two principal questions: the mechanisms of free
      radical-mediated damage in cells and tissue and findings concerning the discovery
      of iron-stimulated free radical cascades in thalassemia and Fanconi anemia. There
      are two major precursors of all reactive oxygen and nitrogen species formed in
      living organism - superoxide (O(2)( -)) and nitric oxide (NO). However, it has
      been shown that in addition to well-known mechanisms of the formation of reactive
      hydroxyl radicals and peroxynitrite from superoxide and NO, there are signal
      pathways by which these "physiological" radicals directly induce apoptosis,
      proton leak in mitochondria and an increase in oxygen consumption leading to cell
      death. In present review the mechanisms of free radical damage are considered
      with the particular emphasis of iron-induced free radical formation in
      thalassemia and Fanconi anemia. Furthermore free radical reactions leading to
      lipid peroxidation, LDL oxidation, the stimulation of apoptosis and other
      damaging processes are discussed. An importance of the chelating and antioxidant
      treatments of thalassemic and Fanconi anemia patients is also considered within
      the context of free radical damage and its prevention.

PMID- 16305469
TI  - Hemoglobin and myoglobin associated oxidative stress: from molecular mechanisms
      to disease States.
AB  - The heme based respiratory proteins myoglobin and hemoglobin can, under certain
      conditions, exhibit a peroxidase-like enzymic activity, in which a catalytic
      cycle, driven by peroxides, leads to oxidation of bio molecules. These heme
      proteins are implicated in what is termed "oxidative stress" as this catalytic
      cycle, when it occurs in vivo, generates cytotoxic product that are implicated in
      the pathology of a number of disease states. Here we review the evidence that
      such reactions occur in vivo, in particular in animal models and human patients
      and examine the underlying chemical mechanism. This mechanism involves the
      production of ferryl heme (Fe(IV)=O(2-)) and it is this and associated radicals
      that initiate processes such as lipid peroxidation and the generation of
      bioactive molecules such as isoprostanes. The reactivity of the high oxidation
      state of the heme also allows us to identify unambiguous biomarkers for its
      presence in vivo in such conditions as rhabdomyolysis and brain hemorrhage. Ways
      to inhibit the peroxidatic cycle are discussed and the role of iron chelators
      such as desferrioxamine is discussed in terms of their often neglected properties
      as reducing agents. Suppression of the peroxidatic activity of hemoglobin is
      discussed in the context of the development of blood substitutes.

PMID- 16305470
TI  - Essentiality, toxicology and chelation therapy of zinc and copper.
AB  - Both zinc and copper are essential minerals that are required for various
      cellular functions. Although these metals are essential, they can be toxic at
      excess amounts, especially in certain genetic disorders. Zinc and copper
      homeostasis results from a coordinated regulation by different proteins involved
      in uptake, excretion and intracellular storage/trafficking of these metals. Apart
      from zinc transporters (ZnT) families and Cu-ATPase, metallothionein is an
      important storage protein for zinc and copper. Metallothioneins are intracellular
      polypeptides with a remarkable ability to bind metallic ions. These proteins bind
      both essential metals indispensable for the organism and also toxic metals (e.g.
      cadmium or lead). Metallothioneins play a critical role to maintain zinc and
      copper homeostasis. In this review, we summarize the toxicity of zinc and copper
      and the potential treatment for zinc or copper toxicity by zinc- or copper
      specific chelators as well as strategy to up-regulate metallothionein.

PMID- 16305471
TI  - Chelating agents used for plutonium and uranium removal in radiation emergency
      medicine.
AB  - The prospects of using chelating agents for increasing the excretion of actinides
      are reviewed. The removal of plutonium by chelating agents is of great importance
      because plutonium is extremely dangerous and induces cancer due to radiation
      toxicity. Similarly, uranium is a radionuclide, which causes severe renal
      dysfunction within a short time period due to chemical toxicity. It may also
      induce cancers such as leukemia and osteosarcoma in cases of long-term internal
      radiation exposure. Investigations on chelating agents for the removal of
      plutonium were initiated in the 1960's and 1970's. Diethylenetriaminepentaacetic
      acid (DTPA) is recognized as a chelating agent that accelerates the excretion of
      plutonium in early treatment after an accident. Thereafter, there has long been
      an interest in finding new chelating agents with radionuclide removal properties
      for use in therapy, and many chelating agents such as 3,4,3-LIHOPO and CBMIDA
      have been studied for their ability to remove plutonium and uranium. Recently,
      the focus has turned to drugs that have been used successfully in the treatment
      of a variety of other diseases, for example the iron chelating drug deferiprone
      or 1,2-dimethyl-3-hydroxypyrid-4-one (L1), which is used in thalassaemia and
      ethane-1-hydroxy-1,1-bisphosphonate (EHBP), which is used in osteoporosis. Within
      this context, it is important to examine the clinical use of these two drugs as
      well as the properties of the experimental chelators 3,4,3-LIHOPO and CBMIDA in
      order to identify possible uses in the treatment of radiation workers
      contaminated with plutonium and uranium.

PMID- 16305472
TI  - Chelators as antidotes of metal toxicity: therapeutic and experimental aspects.
AB  - The effects of chelating drugs used clinically as antidotes to metal toxicity are
      reviewed. Human exposure to a number of metals such as lead, cadmium, mercury,
      manganese, aluminum, iron, copper, thallium, arsenic, chromium, nickel and
      platinum may lead to toxic effects, which are different for each metal. Similarly
      the pharmacokinetic data, clinical use and adverse effects of most of the
      chelating drugs used in human metal poisoning are also different for each
      chelating drug. The chelating drugs with worldwide application are dimercaprol
      (BAL), succimer (meso-DMSA), unithiol (DMPS), D-penicillamine (DPA), N-acetyl-D
      penicillamine (NAPA), calcium disodium ethylenediaminetetraacetate (CaNa(2)EDTA),
      calcium trisodium or zinc trisodium diethylenetriaminepentaacetate (CaNa(3)DTPA,
      ZnNa(3)DTPA), deferoxamine (DFO), deferiprone (L1), triethylenetetraamine
      (trientine), N-acetylcysteine (NAC), and Prussian blue (PB). Several new
      synthetic homologues and experimental chelating agents have been designed and
      tested in vivo for their metal binding effects. These include three groups of
      synthetic chelators, namely the polyaminopolycarboxylic acids (EDTA and DTPA),
      the derivatives of BAL (DMPS, DMSA and mono- and dialkylesters of DMSA) and the
      carbodithioates. Many factors have been shown to affect the efficacy of the
      chelation treatment in metal poisoning. Within this context it has been shown in
      experiments using young and adult animals that metal toxicity and chelation
      effects could be influenced by age. These findings may have a bearing in the
      design of new therapeutic chelation protocols for metal toxicity.

PMID- 16305473
TI  - Soluble paramagnetic chelates and stabilized colloidal particle solutions of iron
      oxides as contrast agents for magnetic resonance imaging.
AB  - The development of contrast agents shortening the relaxation times of protons
      began more than 20 years ago in order to improve the capability of diagnosing
      disease by means of magnetic resonance imaging (MRI). A variety of extracellular
      and tissue specific contrast agents were developed based on two types of
      molecules. One type was related to soluble paramagnetic chelates and the other
      type to stabilized colloidal particle solutions of iron oxides. The chelate or
      metal complex of gadopentetate dimeglumine was the pioneering magnetic resonance
      (MR) contrast agent used in 1988. Chemical modifications of this chelate and the
      design of new chelates led to tissue or blood pool specificity in MRI. Similarly,
      modifications in coating materials and variations in size of iron oxide particles
      allowed for tissue specificity or blood pool properties in MRI. Both types of
      contrast agents offer excellent perspectives for clinical MRI and for molecular
      imaging.

PMID- 16305474
TI  - Advances in DNA-ligands with groove binding, intercalating and/or alkylating
      activity: chemistry, DNA-binding and biology.
AB  - It is known that DNA is a well-characterized intracellular target but its size
      and sequential characteristics make it an elusive target for selective drug
      action. Binding of low molecular weight ligands to DNA causes a variety of
      significant biological responses. In this context the main consideration is given
      to recent developments in DNA sequence selective binding agents bearing
      conjugated effectors because of their potential application in treatment of
      cancers, in diagnosis as well as in molecular biology. In the present review
      recent results about analogues of netropsins, distamycin A and of some
      lexitropsins and combilexins or related hybrid molecules with sequence reading,
      intercalating or alkylating activity are described and evaluated for prospective
      applications. Furthermore there exists DNA minor groove binder with different
      basic structures which does not possess the typical polyamide chain, including
      dimeric intercalating chromophores. Finally new results about peptide nucleic
      acids and related nucleic acid bases linked with polyamides are reported. In
      pronounced examples the structural chemistry, synthesis, DNA binding with several
      biophysical methods, molecular aspects, structure activity relationship,
      topoisomerase inhibition, antitumour and antibacterial effects are discussed in
      detail.

PMID- 16305475
TI  - Based on HLA-DR beta1* allele binding specificities, striking differences in
      distance and TCR Contacting Residue Orientation can be observed in modified
      protection-inducing malarial synthetic peptides.
AB  - An anti-malarial vaccine is urgently needed, especially against P. falciparum
      which causes 2 to 3 million deaths each year, mostly in Sub-Saharan African
      children. This vaccine should contain molecules from the parasite's different
      developmental stages due to the parasite's remarkable complexity and genetic
      variability. The first approach using synthetic peptides from different parasite
      stage molecules (the SPf66 malaria vaccine) conferred limited protective efficacy
      in Aotus monkeys and in large field-trials carried out in different parts of the
      world SPf66 contains red blood cell (RBC) binding merozoite peptides for which
      immune responses against them are genetically controlled by HLA-DR region.
      Therefore, a systematic search of conserved high activity binding peptides (HABP)
      was undertaken aimed at using them as immunogens. However, these peptides were
      poorly immunogenic and had poor protection-inducing capacity against experimental
      challenge with a P. falciparum strain highly infective for Aotus monkeys an
      experimental model with an immune system quite similar to humans. Modifications
      were thus made to key residues to render them immunogenic and protection
      inducing. These native and modified HABPs' three-dimensional structure was
      determined by (1)H-NMR studies and their ability in forming stable Major
      Histocompatibility Class II - peptide (MHCII-peptide) complexes was correlated
      with their ability to bind in vitro to purified HLA-DR beta1* molecules. Our
      experimental data suggests a correlation between modified HABPs' three
      dimensional structure, HLA-DR beta1* binding preferences and their protection
      inducing capacity in monkeys. Furthermore, the data presented here indicates that
      a synthetic peptide vaccine's three-dimensional structural features dictate both
      HLA-DR beta1* allele binding preference (imposing genetic restriction on the
      immune response) and on these vaccines' protection-inducing value. Basic
      knowledge of a parasite's functionally active peptides, their 3D structure and
      their interaction for forming the MHC II- peptide-TCR complex will thus
      contribute towards designing fully effective multi-component, multi-stage subunit
      based malarial vaccines.

PMID- 16305476
TI  - Non-hydroxamate histone deacetylase inhibitors.
AB  - A number of histone deacetylase (HDAC) inhibitors have been developed as
      anticancer agents and most of them are hydroxamic acid derivatives, typified by
      suberoylanilide hydroxamic acid (SAHA), Trichostatin A (TSA) and NVP-LAQ824.
      However, hydroxamic acids have been associated with poor pharmacokinetics and
      severe toxicity. In addition, although isozyme-selective HDAC inhibitors are
      considered useful not only as tools for probing the biology of an enzyme but as
      drugs with low toxicity, many of the hydroxamate HDAC inhibitors do not
      distinguish well among the HDAC isozymes. Thus, there has been considerable
      interest in developing non-hydroxamate HDAC inhibitors. To date, small fatty
      acids, o-aminoanilides, electrophilic ketones, N-formyl hydroxylamines, thiols
      and mercaptoamides have been reported as non-hydroxamate HDAC inhibitors, and
      some of them show antiproliferative activity comparable to hydroxamates.
      Interestingly, hydroxamate HDAC inhibitors such as SAHA and TSA do not
      discriminate well among the HDAC isozymes whereas many non-hydroxamate HDAC
      inhibitors have shown selectivity. These non-hydroxamate HDAC inhibitors should
      pave the way for the development of tools for biological research and new
      medicines with few side effects. In this review, we introduce non-hydroxamate
      HDAC inhibitors describing their design, enzyme inhibition, cancer cell growth
      inhibition and isozyme selectivity.

PMID- 16305477
TI  - The IGF-I/IGF-I receptor pathway: Implications in the Pathophysiology of Thyroid
      Cancer.
AB  - The biological actions of the insulin-like growth factor(IGF)-I are mediated by
      its activation of the IGF-I receptor (IGF-I R), a transmembrane tyrosine kinase
      linked to the Akt and ras-raf-MAPK cascades. A functional IGF-I R is required for
      the cell to progress through the cell cycle. Most importantly, cells lacking this
      receptor cannot be transformed by any of a number of dominant oncogenes, a
      finding that proves that the presence of the IGF-I R is important for the
      development of a malignant phenotype. Consistent with this role, it has been well
      established that IGF-I can protect cells from apoptosis under a variety of
      circumstances. For example, IGF-I prevents apoptosis induced by overexpression of
      c-myc in fibroblasts, by interleukin-3 withdrawal in interleukin-3-dependent
      hemopoietic cells, etoposide, a topoisomerase I inhibitor, anti-cancer drugs, UV
      B irradiations, and serum deprivation. While the anti-apoptotic effect of IGF-I
      has been clearly demonstrated, the molecular mechanisms by which IGF-I inhibits
      apoptosis induced by these various stimuli remain unknown. We have previously
      documented increased IGF-I and IGF-I receptor immunoreactivity in human thyroid
      carcinomas with a corresponding up-regulation of IGF-I mRNA. Immunoreactivity for
      IGF-I and IGF-I receptor positively correlated with tumor diameter, but not with
      the occurrence of lymph node metastases. Several recent studies have identified
      new signaling pathways emanating from the IGF-I receptor that affect cancer cell
      proliferation, adhesion, migration and apoptosis, which represent critical
      functions for cancer cell survival and metastasizing capacity. In this review,
      various aspects of the IGF-I/IGF-I R pathway and its relationship to thyroid
      cancer are discussed.

PMID- 16305478
TI  - Quinone methide derivatives: important intermediates to DNA alkylating and DNA
      cross-linking actions.
AB  - Induced DNA interstrand cross-links by chemical agents or photoactivation play
      very important roles for cancer therapy. Several important clinical drugs (e.g.
      cisplatin, psoralens, and mitomycin C) are known to induce DNA ISC formation,
      which can disrupt cell maintenance and replication. Among these anti-tumor
      agents, one mechanism was involved in quinone methide intermediate. Quinone
      methide derivative has played important roles in organic syntheses as well as in
      chemical and biological processes. This review is concerned with current efforts
      of quinone methide derivatives to DNA alkylation and DNA cross-links. The latest
      advances in this field will be reviewed in this article. The chemical and
      physical properties of quinone methide derivatives, the interactions between
      nucleobases and quinone methide derivatives, the reactions with phosphodiester,
      DNA alkylation and cross-link via quinone methide intermediate action will be
      discussed.

PMID- 16305479
TI  - On the physiological relevance of muscarinic acetylcholine receptors in
      Alzheimer's disease.
AB  - The loss of cholinergic neurons, particularly in the forebrain, plays an
      important role in the pathophysiology of Alzheimer's disease (DAT). This concept
      has lead to the effective treatment of DAT by means of acetylcholine (Ach)
      esterase inhibitors. G-protein-coupled muscarinic acetylcholine receptors (mAchR)
      are classified in 5 subtypes, the M1 receptor stimulation and M2 inhibition being
      especially associated with cognitive skills. Modified cerebral muscarinic
      receptor profiles in patients with Alzheimer's disease in addition to loss of Ach
      releasing neurons help us to understand the pathophysiology of dementia and offer
      potential therapeutic approaches. Specific agonists and antagonists of muscarinic
      receptors are discussed as possible treatment options in DAT. Experimental
      results postulate a positive long lasting modulation of the pathological neuronal
      protein pattern in addition to their cholinomimetic effect.

PMID- 16305480
TI  - Inhibition of PI3K/Akt signaling: an emerging paradigm for targeted cancer
      therapy.
AB  - The phosphatidylinositol 3-kinase (PI3K)/Akt (protein kinase B, PKB) signaling
      pathway plays a critical role in cell growth and survival. Dysregulation of this
      pathway has been found in a variety of cancer cells. Recently, constitutively
      active PI3K/Akt signaling has been firmly established as a major determinant for
      cell growth and survival in an array of cancers. Blocking the constitutively
      active PI3K/AKT signaling pathway provides a new strategy for targeted cancer
      therapy. Thus, inhibitors of this signaling pathway would be potential anticancer
      agents, particularly for cancer cells whose survival and growth are dominated by
      constitutively active PI3K/Akt signaling. This review describes the current
      understanding of small molecule drugs targeting this pathway both in vitro and in
      vivo. Inhibitors and functions of the upstream and downstream molecular targets
      of the PI3K/Akt pathway are discussed in the context of using the inhibitors to
      block this pathway for targeted cancer therapy. Special emphasis is placed on the
      following targets: receptor tyrosine kinases, PI3K, Akt, and the mammalian target
      of rapamycin. While the molecular therapeutic strategy holds great promise for
      the treatment of a variety of cancers, few small molecule inhibitors with
      potential high therapeutic indexes are available. Thus, new inhibitors with high
      selectivity, bioavailability, and potency are greatly needed. Novel approaches
      toward the development of PI3K/Akt pathway inhibitors as anticancer therapeutics
      are discussed in detail, with emphasis on chemical genetics-based and structure
      based drug design.

PMID- 16305481
TI  - Lanthanides as anticancer agents.
AB  - The application of inorganic chemistry to medicine is a rapidly developing field,
      and novel therapeutic and diagnostic metals and metal complexes are now having an
      impact on medical practice. Advances in biocoordination chemistry are crucial for
      improving the design of compounds to reduce toxic side effects and understand
      their mechanisms of action. A lot of metal-based drugs are widely used in the
      treatment of cancer. The clinical success of cisplatin and other platinum
      complexes is limited by significant side effects acquired or intrinsic
      resistance. Therefore, much attention has focused on designing new coordination
      compounds with improved pharmacological properties and a broader range of
      antitumor activity. Strategies for developing new anticancer agents include the
      incorporation of carrier groups that can target tumor cells with high
      specificity. Also of interest is to develop complexes that bind to DNA in a
      fundamentally different manner than cisplatin, in an attempt to overcome the
      resistance pathways that have evolved to eliminate the drug. This review focuses
      on recent advances in developing lanthanide anticancer agents with an emphasis on
      lanthanide coordination complexes. These complexes may provide a broader spectrum
      of antitumor activity. They were compared with classical platinum anticancer
      drugs. Lanthanides are also of interest because of their therapeutic
      radioisotopes. The dominant pharmacological applications of lanthanides are as
      agents in radioimmunotherapy and photodynamic therapy.

PMID- 16305482
TI  - Current drug therapy for prostate cancer: an overview.
AB  - Prostate cancer is the most common cancer amongst men in the USA and the second
      most common malignant cause of male death worldwide after lung cancer. The life
      time risk of having microscopic evidence of prostate cancer for a 50 year old man
      is 42%. Prostate cancer is thus becoming an increasingly significant global
      health problem in terms of mortality, morbidity, as well as economically. This
      review, discusses current medical therapeutic options for prostate cancer
      including traditional treatments using luteinising hormone releasing analogues
      (LHRH), anti-androgens and estrogen treatments, and the use of novel drugs
      directed against molecular targets considered important in oncogenesis and
      metastasis. Prostate cancer chemoprevention using 5alpha-reductase inhibitors and
      the role of gene therapy are also considered.

PMID- 16305483
TI  - Sulfo-quinovosyl-acyl-glycerol (SQAG), a eukaryotic DNA polymerase inhibitor and
      anti-cancer agent.
AB  - It was found that a class of sulfolipids known as sulfo-quinovosyl-acyl-glycerols
      (SQAGs) from ferns and algae are potent inhibitors of eukaryotic DNA polymerase
      alpha and beta and effective anti-neoplastic agents. In developing a procedure
      for the chemical synthesis of sulfolipids, many derivatives and stereoisomers of
      SQAGs have been obtained including sulfo-quinovosyl-monoacyl-glycerols (SQMGs)
      and sulfo-quinovosyl-diacyl-glycerols (SQDGs). This review describes studies on
      the structure-function relationship between synthetic SQAGs and DNA polymerase
      alpha and beta, and the relationship to cytotoxic activity. The major action was
      probably dependent on the fatty acid effect, which was reported previously,
      although each of the SQAGs was a much stronger inhibitor than just the fatty acid
      present in the SQAGs. The inhibitory effect could be influenced by the chain size
      of fatty acids in the SQAGs. The sulfonyl group in quinovose was also needed to
      inhibit the enzymes. Lineweaver-Burk plots of SQAGs indicated that DNA polymerase
      alpha was non-competitively inhibited, but the SQAGs were effective as
      antagonists of both the template-primer DNA-binding and the nucleotide substrate
      binding of DNA polymerase beta. Based on these results, the molecular actions of
      SQAGs and drug design strategies for developing new anti-neoplastic agents were
      discussed.

PMID- 16305484
TI  - Lycopene: a review of its potential as an anticancer agent.
AB  - Dietary chemoprevention has emerged as a cost effective approach to control most
      prevalent chronic diseases including cancer. In particular, tomato and tomato
      products are recognised to confer a wide range of health benefits.
      Epidemiological studies have provided evidence that high consumption of tomatoes
      effectively lowers the risk of reactive oxygen species (ROS)-mediated diseases
      such as cardiovascular disease and cancer by improving the antioxidant capacity.
      Tomatoes are rich sources of lycopene, an antioxidant carotenoid reported to be a
      more stable and potent singlet oxygen quenching agent compared to other
      carotenoids. In addition to its antioxidant properties, lycopene shows an array
      of biological effects including cardioprotective, anti-inflammatory,
      antimutagenic and anticarcinogenic activities. The anticancer activity of
      lycopene has been demonstrated both in in vitro and in vivo tumour models. The
      mechanisms underlying the inhibitory effects of lycopene on carcinogenesis could
      involve ROS scavenging, upregulation of detoxification systems, interference with
      cell proliferation, induction of gap-junctional communication, inhibition of cell
      cycle progression and modulation of signal transduction pathways. This review
      outlines the sources, structure, absorption, metabolism, bioavailability and
      pharmacological properties of lycopene with special reference to its antioxidant
      and anticarcinogenic effects.

PMID- 16305486
TI  - Targeted therapy in hematologic maligancies--progress made, lessons learned?

PMID- 16305485
TI  - Selenium derivatives as cancer preventive agents.
AB  - The role of selenium in the prevention of cancer has been recently established by
      laboratory experiments, clinical trials, and epidemiological data. Most of the
      effects are related to the function of selenium in antioxidant enzyme systems.
      Animal data, epidemiological data, and intervention trials have shown a clear
      role for selenium derivatives in both prevention of specific cancers and
      antitumorigenic effects in postinitiation phases of cancer. Consequently,
      selenium supplementation has moved from the realm of correcting nutritional
      deficiencies to one of pharmacological intervention, especially in the clinical
      domain of cancer chemoprevention. Accordingly, there has been substantial
      interest directed toward the synthesis of selenium-containing derivatives in
      recent years that could be used as cancer chemopreventive agents. The current
      review aims to outline recent developments in the application of selenium
      derivatives as cancer preventive agents.

PMID- 16305487
TI  - Angiogenesis in lymphoma: a short review.
AB  - It is now well established that the growth of primary and metastatic tumors is
      associated with the formation of new blood vessels, and that the growth of these
      tumor cells is frequently dependent on this neovasculature. The observation that
      inhibition of tumor angiogenesis in mice can lead to tumor regression or dormancy
      generated high level of enthusiasm and interest in developing new treatment
      strategies for human cancer based on inhibiting tumor angiogenesis. This short
      review focuses on recent advances in angiogenesis-research in non-Hodgkin's
      lymphoma and Hodgkin's disease.

PMID- 16305488
TI  - Targeting the kinase activity of the BCR-ABL fusion protein in patients with
      chronic myeloid leukemia.
AB  - Imatinib mesylate is a major advance in the therapy of patients with chronic
      myelogenous leukemia (CML). Imatinib mesylate binds to the inactive conformation
      of BCR-ABL tyrosine kinase suppressing the Philadelphia chromosome positive clone
      in CML. Clinical studies have yielded impressive results in all phases of CML.
      With higher rates of complete cytogenetic response with imatinib, molecular
      monitoring of disease is now advisable in assessing response and determining
      prognosis. Emergence of resistance to imatinib may be manifest at the
      hematologic, cytogenetic, or molecular levels in patients who remain in chronic
      phase, or may be evidenced by the development of more advanced CML phases.
      Resistance and eventual clinical failure of imatinib occurs in most patients with
      blastic phase disease. Resistance may occur at the level of Bcr-Abl, with
      reduction or loss of imatinib effectiveness as a kinase inhibitor, or, despite
      retention of its inhibitory ability, with changes in the ability to deliver an
      effective dose at the cellular level, and/or, the leukemia becoming less
      dependent on Bcr-Abl. The various mechanisms underlying these differing, non
      mutually exclusive, mechanisms of resistance must be understood to develop
      corresponding therapeutic remedies. We review the current data on imatinib in
      CML, the criteria for diagnosis of imatinib resistance, and the mechanisms that
      underlie such resistance in CML.

PMID- 16305489
TI  - Kinases as drug discovery targets in hematologic malignancies.
AB  - Protein kinases have emerged as one of the most promising targets for rational
      drug discovery. In a similar manner to imatinib mesylate (Gleevec), hematological
      malignancies offer multiple pharmacologic opportunities for manipulation of
      kinase-induced tumor cell proliferation. Certain kinases have been validated as
      targets for drug discovery in hematological malignancies (such as BCR-ABL and
      FLT3); other novel kinases hold considerable interest for targeted intervention:
      myeloid leukemias (KDR, KIT, CSF-1R, RAS and RAF), lymphoid leukemias (JAK2
      fusion protein, TIE-1, CDK modulators), lymphoma (ALK, CDK modulators, mTOR),
      myeloproliferative disorders (PDGF-R or FGF-R fusion gene products, FGF-R1) and
      myeloma (FGF-R3, STAT3). Over the past five years, the number of kinase-targeted
      drug therapies undergoing clinical development has increased exponentially. This
      review will focus on novel kinase targets currently undergoing preclinical and
      clinical investigation.

PMID- 16305490
TI  - Targeting the process of farynesylation for therapy of hematologic malignancies.
AB  - In sum, the FTIs are signal transduction inhibitors that display promising
      clinical activity against a broad spectrum of malignancies. We are just beginning
      to explore and elucidate the mechanisms by which transformed cells respond to
      FTIs and the optimal settings in which they do so. The clinical trials that are
      currently in progress and under development will provide the critical foundations
      for defining the optimal roles of FTIs in patients with AML and other hematologic
      disorders. The correlative laboratory studies to define the mechanisms by which
      FTIs alter cellular metabolism and modulate the activities of specific signaling
      pathways in both normal and malignant marrow precursors are a pivotal part of
      this effort. What we learn about FTIs in the clinic and the laboratory will apply
      broadly to the effective and safe application of all signal transduction
      inhibitors.

PMID- 16305491
TI  - Mammalian target of rapamycin as a therapeutic target in leukemia.
AB  - Reflecting its critical role in integrating cell growth and division with the
      cellular nutritional environment, the mammalian target of rapamycin *(mTOR) is a
      highly conserved downstream effector of the phosphatidylinositol 3-kinase
      (PI3K)/Akt (protein kinase B) signaling pathway. mTOR activates both the 40S
      ribosomal protein S6 kinase (p70s6k) and the eukaryotic initiation factor 4E
      binding protein-1. As a consequence of inhibiting its downstream messengers, mTOR
      inhibitors prevent cyclin-dependent kinase (CDK) activation, inhibit
      retinoblastoma protein phosphorylation, and accelerate the turnover of cyclin D1,
      leading to a deficiency of active CDK4/cyclin D1 complexes, all of which may help
      cause GI phase arrest. Constitutive activation of the PI3K/Akt kinases occur in
      human leukemias. FLT3, VEGF, and BCR-ABL mediate their activities via mTOR. New
      rapamycin analogs including CCI-779, RAD001, and AP23573, are entering clinical
      studies for patients with hematologic malignancies.

PMID- 16305492
TI  - Monoclonal antibodies in the treatment of leukemia.
AB  - MoAb-based therapies are evolving into the first broad-spectrum class of targeted
      anti-leukemic therapy. Developments in many areas, including computer modeling of
      receptors and ligands, and increasing sophistication in recombinant technologies
      may result in a rapid increase in the number and complexity of MoAb's available.
      We can anticipate an increase in the number of safer conjugates being delivered
      to leukemia cells. Further understanding of the in vitro mechanisms involved in
      tumor cell killing by MoAb will be important in maximizing the efficacy of this
      approach.

PMID- 16305493
TI  - SARS: understanding the virus and development of rational therapy.
AB  - In late 2002 a new disease, severe atypical respiratory syndrome (SARS), emerged
      in China. A hitherto unknown animal coronavirus (CoV) that had crossed the
      species barrier through close contact of humans with infected animals was
      identified as the etiological agent. It rapidly adapted to the new host and not
      only became readily transmissible between humans but also more pathogenic. Air
      travel spread it rapidly around the world and ultimately the virus infected 8096
      people and caused 774 deaths in 26 countries on 5 continents. Aggressive
      quarantine measures successfully terminated the disease. Currently, there are no
      SARS cases recorded and most likely the virus no longer circulates in the human
      population. In this review we present an overview over SARS-Co virus biology, the
      disease and discuss strategies to develop antiviral drugs and vaccines.

PMID- 16305494
TI  - Craniofacial anomalies: from development to molecular pathogenesis.
AB  - Advances in developmental biology combined with progress in human genetics are
      helping us decipher how the craniofacial region develops and how the consequences
      of misdirected development result in malformation. This review describes the
      molecular etiology of a number of craniofacial developmental anomalies. The more
      common craniofacial anomalies cleft lip and palate and craniosynostosis, as well
      as cleidocranial dysplasia, hemifacial microsomia, holoprosencephaly, enlarged
      parietal foramina, Treacher Collins syndrome and cherubism are discussed.

PMID- 16305495
TI  - Marrow stromal cells: implications in health and disease in the nervous system.
AB  - Chronic degenerative diseases and traumatic injuries are responsible for a
      decline in neuronal function, which often limit life span. While solid organ
      transplantation such as liver and kidney has been already applied for thousands
      of patients, great limitation exists in case of nervous system. Cell
      transplantation is one of the strategies with potential for treatment of such
      neural disorders, and many kinds of cells including embryonic stem cells and
      neural stem cells have been considered as candidates for transplantation therapy.
      Bone marrow stromal cells (MSCs) have great potential as therapeutic agents,
      since they are easy to isolate and can be expanded from patients without serious
      ethical and technical problems. We found a method for the highly efficient and
      specific induction of functional neurons and Schwann cells from both rat and
      human MSCs. Induced neurons and Schwann cells were transplanted in animal models
      of Parkinson's disease, stroke, peripheral nerve injury, and spinal cord injury
      resulting in the successful integration of transplanted cells and improvement in
      behavior of transplanted animals. Here we focus on the respective potentials of
      MSC-derived cells and discuss the possibility of clinical application in
      neurodegenerative and neurotraumatic diseases.

PMID- 16305497
TI  - Cell-penetrating peptides: mechanisms and applications.
AB  - A major obstacle in the development of new therapeutic agents is the low
      bioavailability of hydrophilic substances. Drugs that bind to intracellular
      targets must penetrate the lipid bilayer surrounding the cell in order to exert
      their effect. A relatively new research area that addresses this problem by
      introducing novel transport peptides that facilitate the cellular penetration of
      potential drugs has emerged. These peptides predominantly have a positive net
      charge and/or an amphipathic nature, but can otherwise have very different
      characteristics. This group of peptides, although sometimes called protein
      transduction domains (PTDs), is here referred to as cell-penetrating peptides
      (CPPs). For many years it was believed that these peptides were internalized into
      cells via a non-endocytotic, receptor-independent pathway. However, recent
      publications have suggested that an endocytotic pathway cannot be ruled out, and
      that earlier results might be based on artifacts associated with fixation of
      cells and membrane association of peptides. Although the mechanism of cellular
      uptake remains unclear, there is an increasing amount of reports on biological
      effects of CPPs and their cargos. Thus, CPPs are an attractive pharmaceutical and
      biochemical tool that needs more attention. This review will discuss some recent
      results in this research field with focus on the cell-penetrating peptide
      transportan.

PMID- 16305498
TI  - Endocytosis and cationic cell-penetrating peptides--a merger of concepts and
      methods.
AB  - With the identification of fixation as a major source of artefacts in the cell
      biological research on cell-penetrating peptides (CPPs), the past two years have
      witnessed a dramatic development in the CPP field. At least for some of these
      molecules, endocytosis is now considered to be the major if not the exclusive
      route of cellular import. However, endocytosis comprises a variety of different
      pathways with very different implications for the delivery of bioactive molecules
      to the cytoplasm and nucleus. The endocytosis of CPPs is governed by complex
      mechanisms similar to those responsible for the internalization of other
      molecules. Therefore the investigation of uptake and intracellular trafficking of
      CPPs can benefit enormously from the understanding of the endocytic machinery as
      well as from the tools that have already been developed for the analysis of
      endocytosis. This review will introduce aspects of endocytosis relevant to the
      analysis of CPPs. In addition to the methods, that have already been used for the
      analysis of CPP trafficking, we will also present other tools and approaches
      which can be helpful for the research of CPP uptake. Furthermore this review will
      analyze and summarize recent data providing new insights in endocytosis and
      intracellular trafficking of CPPs.

PMID- 16305499
TI  - Interactions of primary amphipathic cell penetrating peptides with model
      membranes: consequences on the mechanisms of intracellular delivery of
      therapeutics.
AB  - This review focuses on two peptides, MPG and Pep-1, which facilitate the transfer
      of nucleic acids and proteins, respectively, into subcellular compartments. We
      have investigated the interactions between these two carrier peptides and model
      membrane systems as well as the conformational consequences of these
      interactions. Studies performed with lipid monolayers at the air-water interface
      have enabled identification of the nature of the lipid-peptide interactions and
      characterization of the influence of phospholipids on the ability of these
      peptides to penetrate into lipidic media. Penetration and compression experiments
      reveal that both peptides interact strongly with phospholipids, and observations
      on Langmuir-Blodgett transfers indicate that they can modify the lipid
      organization. Conformational investigations indicate that the lipid-peptide
      interaction govern the conformational state of the peptides. Based on the ability
      of both peptides to promote ion permeabilization of both natural and artificial
      membranes, we propose a model illustrating the translocation process. For MPG it
      is based on the formation of a beta-barrel pore-like structure while for Pep-1 it
      is based on association of helices.

PMID- 16305500
TI  - Conjugates of oligonucleotides and analogues with cell penetrating peptides as
      gene silencing agents.
AB  - The review describes key aspects of the synthesis and biological activities of
      conjugates of oligonucleotides and their analogues with synthetic peptides, in
      particular aimed towards gene silencing applications. The common methods of
      synthesis of oligonucleotide-peptide conjugates (OPCs) and PNA-peptide conjugates
      (PPCs) are described, which include both total solid-phase and fragment coupling
      approaches. In addition, various applications of conjugates as gene silencing
      agents are outlined. These include antisense and steric block applications in
      mammalian cells of OPCs, PPCs and phosphorodiamidate morpholinooligonucleotide
      (PMO)-peptide conjugates, gene silencing in bacteria, various DNA targeting
      applications, and recent reports of gene silencing activities of siRNA-peptide
      conjugates. A table listing all peptides used as oligonucleotide conjugates for
      gene silencing applications is also included.

PMID- 16305501
TI  - Vascular homing peptides with cell-penetrating properties.
AB  - In vivo screening of phage-displayed peptide libraries has revealed extensive
      molecular heterogeneity in the blood vessels of individual normal tissues and
      shown that pathological lesions put their signature on the vasculature. In
      tumors, both blood and lymphatic vessels differ from normal vessels. Moreover,
      the molecular changes in the vasculature parallel progression in tumor
      development, hence making the vessels in premalignant lesions distinguishable
      from normal vessels and from the vessels in malignant tumors of the same tissue.
      Some of the tumor-homing peptides penetrate into tumor endothelial cells (and
      tumor cells), but not into endothelial cells in normal tissues or other normal
      cells. Thus, these cell-penetrating peptides are cell type-specific. Peptides
      that home to tumor vasculature have been shown to be useful in directing
      therapeutic agents to experimental tumors. The cell penetrating peptides may be
      particularly useful in drug delivery because they can take their payload inside
      the target cells and even into a specific subcellular organelle such as the
      nucleus.

PMID- 16305502
TI  - Calcitonin-derived carrier peptides.
AB  - The recent discovery of carrier peptides offers new opportunities to translocate
      several bioactive molecules into the cytoplasm. Previous studies have shown that
      human calcitonin (hCT) and selected C-terminal sequences translocate in nasal
      epithelium. Moreover, the hCT(9-32) fragment was found to internalize efficiently
      a number of substances like fluorophores, nucleic acids or the enhanced green
      fluorescent protein (EGFP). In order to understand the uptake mechanism
      interactions of hCT(9-32) with membrane models of different lipid compositions
      have been investigated. From these studies it was possible to shed light on the
      conformational state of the peptide in the presence of membrane-like conditions.
      Further insight into the translocation mechanism was provided by fluorescence
      microscopy of truncated sequences of hCT that were shown to penetrate the plasma
      membrane and to distribute in a sectoral, punctuated pattern supporting an
      endocytotic internalization pathway as previously suggested.

PMID- 16305503
TI  - Bioplex technology: novel synthetic gene delivery pharmaceutical based on
      peptides anchored to nucleic acids.
AB  - Non-viral gene delivery is an important approach in order to establish safe in
      vivo gene therapy in the clinic. Although viral vectors currently exhibit
      superior gene transfer efficacy, the safety aspect of viral gene delivery is a
      concern. In order to improve non-viral in vivo gene delivery we have designed a
      pharmaceutical platform called Bioplex (biological complex). The concept of
      Bioplex is to link functional entities via hybridising anchors, such as Peptide
      Nucleic Acids (PNA), directly to naked DNA. In order to promote delivery
      functional entities consisting of biologically active peptides or carbohydrates,
      are linked to the PNA anchor. The PNA acts as genetic glue and hybridises with
      DNA in a sequence specific manner. By using functional entities, which elicit
      receptor-mediated endocytosis, improved endosomal escape and enhance nuclear
      entry we wish to improve the transfer of genetic material into the cell. An
      important aspect is that the functional entities should also have tissue
      targeting properties in vivo. Examples of functional entities investigated to
      date are the Simian virus 40 nuclear localisation signal to improve nuclear
      uptake and different carbohydrate ligands in order to achieve receptor specific
      uptake. The delivery system is also endowed with regulatory capability, since the
      release of functional entities can be controlled. The aim is to create a safe,
      pharmaceutically defined and stable delivery system for nucleic acids with
      enhanced transfection properties that can be used in the clinic.

PMID- 16305504
TI  - Direct interaction of dietary lipids carried in chylomicron remnants with cells
      of the artery wall: implications for atherosclerosis development.
AB  - The development of atherosclerotic lesions in the artery wall is a complex
      process involving the endothelium, lipid engorged macrophages (foam cells) and
      smooth muscle cells. In recent years it has become clear that chylomicron
      remnants, the lipoproteins which carry lipids of dietary origin in the blood, are
      strongly atherogenic, and there is increasing evidence to indicate that this is
      due to direct interaction of the remnant particles with cells of the artery wall.
      Chylomicron remnants have been demonstrated to inhibit endothelium dependent
      vasorelaxation and to activate signal transduction pathways associated with
      inflammation in cultured endothelial cells. They have also been shown to be taken
      up by smooth muscle cells and macrophages, and to cause the extensive lipid
      accumulation associated with foam cell formation, as well as influencing the
      expression of key genes regulating macrophage lipid uptake and metabolism.
      Furthermore, oxidative modification of the remnant particles is not required for
      many of these effects. Chylomicron remnants, therefore, have multiple direct
      effects on three major cell types of the arterial wall which are likely to
      promote the development of atherosclerotic lesions. These effects may be
      modulated by various lipids carried by the particles, including the type of fat
      (saturated or unsaturated or oxidised fat), micronutrients such as vitamins and
      carotenoids which have antioxidant properties, and orally administered lipophilic
      drugs. Delayed clearance of chylomicron remnants from the blood occurs in a
      number of dyslipidemias associated with premature atherosclerosis development,
      and the potentially atherogenic effects of the particles would clearly be
      enhanced in these circumstances. Thus, elucidation of the mechanisms involved
      will aid in the identification of new drug targets which may be particularly
      useful for these conditions.

PMID- 16305505
TI  - Hepatotoxicity of antiretroviral drugs.
AB  - The use of highly active antiretroviral therapy (HAART) has significantly slowed
      the HIV disease progression. However, adverse effects are now a limiting cause of
      HAART benefit in a substantial proportion of patients. Particularly
      hepatotoxicity which is a common complication occurring during every HAART
      regimen. All antiretroviral (ARV) drugs classes, Nucleoside/Nucleotide reverse
      transcriptase inhibitors (NRTI), non-Nucleoside reverse transcriptase inhibitors
      (nNRTI) and Protease Inhibitors (PI) may cause hepatotoxicity but in different
      pathways. Many risk factors have been identified for developing antiretroviral
      related hepatotoxicity, however severe hepatitis remains very uncommon in
      patients receiving HAART, also if the incidence of hepatotoxicity is rather high.
      That being the case, means that every new available antiretroviral drug strongly
      necessities studies which can evaluate its hepatotoxicity and drug-drug
      interactions, to define the potential risk factors and the outcome of any side
      effects. This report will review the risk factors, the epidemiology and the
      pathogenic mechanisms of hepatotoxicity caused in every antiretroviral drug.

PMID- 16305506
TI  - Oral and intravenous ibandronate in the management of postmenopausal
      osteoporosis: a comprehensive review.
AB  - Convenient strategies are needed for postmenopausal osteoporosis management.
      Current oral bisphosphonates are effective and generally well tolerated, but are
      hampered by strict dosing requirements. Less frequent dosing schedules are
      expected to improve adherence to therapy and hence outcomes. Ibandronate is a
      potent, nitrogen-containing bisphosphonate in ongoing clinical development
      exploring its potential to be administered less frequently than at weekly
      intervals. Uniquely, ibandronate can be administered either orally or as an
      intravenous (i.v.) injection, with a between-dose interval of >2 months. In
      postmenopausal women, oral ibandronate, when administered either daily or
      intermittently, has demonstrated robust antifracture efficacy at the spine (62%
      [p=0.0001] and 50% [p=0.0006] risk reduction versus placebo), accompanied by
      significant increases in bone mineral density (BMD) at the spine and hip, and
      suppression of bone turnover markers. Studies of intermittent i.v. ibandronate
      injections in postmenopausal women have shown dose-related BMD gains and bone
      turnover marker suppression comparable to those obtained after a similar duration
      of treatment with the proven effective oral ibandronate regimen. Furthermore, in
      a trial conducted in patients with corticosteroid-induced osteoporosis,
      intermittent i.v. ibandronate injections reduced vertebral fracture risk by 62%
      versus an active control (p=0.043). In all these trials, the oral and i.v.
      ibandronate regimens were well tolerated. Ongoing, large multinational clinical
      trials are investigating two intermittent ibandronate regimens: once-monthly oral
      and intermittent i.v. injections. These simple ibandronate regimens are expected
      to provide the optimal combination of efficacy, tolerability and patient
      convenience, leading to improved treatment adherence and thus, enhanced outcomes
      in postmenopausal osteoporosis.

PMID- 16305508
TI  - Microbicides for prevention of transmission of sexually transmitted diseases.
AB  - In the last 50 years, changes in cultural and scientific realities and customs
      have resulted in a worldwide epidemic of sexually transmitted diseases (STD).
      This is a multi-factorial problem resulting in part from: 1) an increased
      permissiveness in sexual attitudes in the Western world that results in earlier
      onset of intercourse and increased numbers of partners and types of sex acts; 2)
      a global transportation network that facilitates contacts and interactions
      between urban and rural areas as well as between countries resulting in migration
      and spread of infections; 3) an emergence of new and mutated forms of pathogens
      with increased capabilities to cause infections and for which there are no
      available vaccines or therapies; and, 4) at risk populations in developing
      countries who are susceptible to these pathogens while having societal
      infrastructures that lack basic health education and proper access to healthcare.
      Overwhelming examples of increasing and emerging STD pathogens exist in the early
      twenty-first century. These include human immunodeficiency virus type 1 (HIV-1),
      the causative agent of acquired immunodeficiency syndrome (AIDS), with over 42
      million current cases of infection, 20 million deaths to date, and an estimated
      500,000 deaths per year; human papillomavirus (HPV) infections, the causative
      agents of genital warts and cervical cancer, with approximately 1 in 4 women
      harboring virus DNA in genital epithelium, 1-3 percent of women showing symptoms
      of infection and 250,000 deaths per year in women worldwide from cervical cancer;
      and numerous others. Topical microbicides have been proposed as agents to break
      the chain of transmission in these infections by providing chemical, biological,
      and/or physical barriers to infection by blocking and/or inactivating pathogens
      at the mucosal surface where infection can occur. For many sexually transmitted
      infections, vaccines do not exist, and therapeutic agents are only partially
      effective, expensive, and difficult to distribute. In addition, female partners
      in many relationships do not control pregnancy or STD risk and may benefit from
      discrete methods, other than condoms, that would provide protection. Thus,
      microbicides should be valuable additions to preventing these diseases if they
      can be shown effective. Currently, 62 microbicides are in development with 6
      entering Phase III clinical trials, 11 entering Phase I clinical trials, and 44
      in pre-clinical development. In this review, we will describe many of the
      principles of microbicide mechanisms and give examples of major types of
      microbicides and their actions. Space precludes a complete description of all of
      the agents and their mechanisms of action. We will also put forth the argument
      for alkyl sulfate microbicides, including sodium dodecyl sulfate (SDS), agents
      that are in active development in our laboratories.

PMID- 16305509
TI  - Anti-HIV-1 microbicides -- 'chemical condoms' designed to limit the scourge of
      the HIV-1 pandemic.
AB  - The HIV pandemic continues to spread throughout the world, particularly affecting
      populations in developing countries. Women now comprise half of those infected.
      Efforts to limit this scourge need to be maximally implemented. A multi-faceted
      approach, including the research and advance of microbicides - or 'chemical
      condoms' - offers promise. Microbicides are self-administered, prophylactic
      products designed to protect against sexually transmitted pathogens, including
      HIV-1. Important features include safety, efficacy and user acceptability. This
      review summarizes some of the important products in the development pipeline.

PMID- 16305510
TI  - Toward a design of affordable, topical microbicides: acylcarnitine analogues.
AB  - Most heterosexual women want to reduce the risk of acquiring a sexually
      transmitted infection; many also want to control their fertility. Several
      chemical agents have been proposed to dramatically slow the spread of HIV
      infections. Ideally, vaginal microbicides, with or without contraceptive
      properties, should be safe, effective, and affordable for women everywhere.
      Amphiphiles, which are surfactants that can act as detergents, have a long
      history as microbicides against many pathogens. Amphiphiles have several
      desirable traits; e.g., they are inexpensive, fast-acting, and capable of a broad
      spectrum of activity. An "ideal" amphiphilic microbicide will rapidly and
      selectively inactivate pathogens and sperm without irritating tissue. In this
      review, we discuss a homologous series of amphiphilic acylcarnitine analogues as
      microbicides. Two homologues, Z-14 and Z-15, possess excellent spermicidal, anti
      HIV, anti-chlamydial, anti-gonorrhea, and anti-Haemophilus activities; both have
      outstanding anti-Candida activity. A 4% Z-15 gel that is comprised of 3%
      carboxymethylcellulose in water gives a dramatically low score in a rabbit
      vaginal-irritation study. The mechanisms of action of these compounds are not
      fully understood as yet, but we present several possibilities. Moreover, the
      results of our limited structure-activity study with a homologous series have
      stimulated additional questions and ideas for designing the next generation of
      microbicidal amphiphiles. The above studies support the idea that Z-14 and Z-15
      can potentially serve as safe (non-irritating), effective topical microbicides.

PMID- 16305511
TI  - Preclinical studies of alkylureas as anti-HIV-1 contraceptive.
AB  - The HIV-1 epidemic continues to spread at a rate of over 15, 000 new cases daily.
      HIV-1 transmission through heterosexual contact became the dominant risk for
      women globally. About half of the over 40 million HIV-1 infected individuals
      worldwide are now women. The lack of empowerment of women is the fundamental
      cause for the rampant spread of HIV-1 in women. Topical microbicides applied
      intravaginally offer an option for female-initiated HIV-1 prevention. There is an
      urgent need to develop microbicides with and without contraceptive qualities to
      also address socio-cultural settings where the woman's status is linked to
      fertility. A safe and efficacious anti-HIV-1 vaginal formulation is not yet
      available though a large number of candidates are in preclinical or clinical
      studies. Presently marketed topical microbicides are by and large toxic and
      damage the vaginal mucosa with frequent use. The microbicidal system of
      alkylureas evaluated here lends itself to contraceptive and non-contraceptive
      anti- HIV-1 formulations. Alkylureas are agents that irreversibly disrupt free
      and intracellular HIV-1, have a wide margin of safety and are spermicidal above
      their virucidal concentration without any mucosal toxicity. Butylurea, the lead
      compound is also effective against other sexually transmitted diseases (STDs)
      while sparing the normal vaginal flora. Alkylureas with longer alkyl chains still
      have to be explored and may have a greater selective microbicidality.

PMID- 16305512
TI  - Indolyl aryl sulfones (IASs): development of highly potent NNRTIs active against
      wt-HIV-1 and clinically relevant drug resistant mutants.
AB  - Indolyl aryl sulfones (IASs) are a potent class of NNRTIs developed from L
      737,126, a lead agent discovered by Merck AG. IAS derivatives are endowed with
      inhibitory activities against wt HIV-1 in the low nanomolar concentration range.
      Introduction of two methyl groups at positions 3 and 5 of the phenyl ring of the
      aryl sulfonyl moiety furnished IAS derivatives such as 5-chloro- or 5-bromo-3
      [(3,5-dimethylphenyl)sulfonyl]indole-2-carboxyamide, which showed very potent and
      selective anti-HIV-1 activity against some mutants carrying NNRTI resistant
      mutations at positions 103 and 181 of the reverse transcriptase. IAS derivatives
      bearing 2-hydroxyethylcarboxyamide or 2-hydroxyethylcarboxyhydrazide groups at
      position 2 of the indole nucleus were more active than L-737,126 against the
      K103N-Y181C double mutant. A great improvement of antiviral activity against wt
      HIV-1 and resistant mutants was obtained by coupling 1-3 simple amino acids, such
      as glycine and alanine, in sequence, with the 3-[(3,5-dimethylphenyl)sulfonyl]-1H
      indole-2-carbonyl moiety. The transformation of the chain terminus into amide or
      hydrazide, produced short peptides with high selectivity and potent activity
      against wt HIV-1, and the viral mutants Y181C, K103N-Y181C and EFV(R). IAS having
      two halogen atoms at the indole showed potent inhibitory activity against the
      Y181C and the EFV(R) resistant mutant strains. In particular, the introduction of
      a fluorine atom at position 4 of the indole ring notably contributed to improve
      the antiviral activities against both wt and the related resistant mutants. 5
      Nitro-IASs were highly active against wt HIV-1 and exhibited low cytotoxicity.
      Experimental data highlighted the class IAS derivatives as promising candidates
      for clinical trials.

PMID- 16305513
TI  - Ubiquitin-proteasome pathway components as therapeutic targets for CNS maladies.
AB  - In the central nervous system (CNS), abnormal deposition of insoluble protein
      aggregates or inclusion bodies within nerve cells is commonly observed in
      association with several neurodegenerative diseases. The ubiquitinated protein
      aggregates are believed to result from malfunction or overload of the ubiquitin
      proteasome pathway or from structural changes in the protein substrates which
      prevent their recognition and degradation by the ubiquitin-proteasome pathway.
      Impaired proteolysis might also contribute to the synaptic dysfunction seen early
      in neurodegenerative diseases because the ubiquitin-proteasome pathway is known
      to play a role in normal functioning of synapses. Because specificity of the
      ubiquitin proteasome mediated proteolysis is determined by specific ubiquitin
      ligases (E3s), identification of specific E3s and their allosteric modulators are
      likely to provide effective therapeutic targets for the treatment of several CNS
      disorders. Another unexplored area for the discovery of drug targets is the
      proteasome. Although many inhibitors of the proteasome are available, no
      effective drugs exist that can stimulate the proteasome. Since abnormal protein
      aggregation is a common feature of different neurodegenerative diseases,
      enhancement of proteasome activity might be an efficient way to remove the
      aggregates that accumulate in the brain. In this review, we discuss how the
      components of the ubiquitin-proteasome pathway could be potential targets for
      therapy of CNS diseases and disorders.

PMID- 16305514
TI  - Drug tissue distribution: study methods and therapeutic implications.
AB  - Current interest in studies on tissue distribution stems from the limited
      capacity to predict tissue concentrations and the pharmacological response from
      plasma drug levels, and from the limitations - both methodological and
      deontological- involved in doing so, especially in humans. In this review we
      carry out a comparative analysis of the methods used for studying tissue
      distribution, placing special focus on recently developed non-invasive methods
      for the research of tissue distribution in humans, such as positron emission
      tomography and nuclear magnetic resonance spectroscopy. We describe the
      strategies of tissue distribution pharmacokinetic analysis that have evolved from
      analysis based on compartment and physiological models to analyses based on
      spatial and fractal models and, mainly, pharmacokinetic-pharmacodynamic models.
      Model-independent analysis based on the use of mean transit times or
      deconvolution strategies has become a good alternative for the pharmacokinetic
      analysis of tissue distribution. The need to increase the selectivity of many
      drugs justifies the desire to gain further insight into the design of new
      analogues prodrugs and carrier systems that will guarantee the specific delivery
      of a given drug to a particular organ or tissue, optimising the response. In
      silico models for drug distribution have become a helpful tool in drug discovery
      and development. The therapeutic implications of drug tissue distribution are
      also analysed, special reference being made to antiretroviral therapy and
      antitumoural gene therapy, among others.

PMID- 16305515
TI  - The antiviral activity, mechanism of action, clinical significance and resistance
      of abacavir in the treatment of pediatric AIDS.
AB  - The novel carbocyclic nucleoside, abacavir, is metabolized in cells to carbovir
      triphosphate which is a potent inhibitor of HIV reverse transcriptase (K(i) 0.021
      microM with calf thymus DNA template primer). Abacavir exhibits potent in vitro
      antiviral activity against wild-type HIV-1 (IC(50) 4.0 microM, MT-4 cells) but
      this activity is lower than the activity of AZT (IC(50) 0.040 microM, MT-4
      cells). However, there is no significant difference between the levels of
      activity of abacavir (IC(50) 0.26 microM) and AZT (IC(50) 0.23 microM) against
      clinical isolates of HIV-1. The in vitro toxicity data (CC(50)) of abacavir were:
      160 microM (CEM cells); 140 microM (CD4+ CEM cells) and 110 microM (normal bone
      progenitor cells, BFU-E). Abacavir has been approved in the United States for the
      treatment of pediatric and adult HIV infection and current recommendations
      consist of combination therapy in children with HIV infection. Resistance to
      abacavir develops relatively slowly, with most of the mutations conferring
      minimal resistance. The M184V mutation appears to be the cornerstone of higher
      level resistance in regimens containing abacavir, imparting a 2-4 fold reduction
      in the susceptibility of HIV to abacavir.

PMID- 16305517
TI  - Heterogeneity of synthetic factor Xa inhibitors.
AB  - Heparins and vitamin K antagonists are the landmarks of antithrombotic treatment.
      Both of them were discovered by serendipity; they are multi-targeted drugs and
      share several limitations. New molecules have been designed in order to be both
      more selective concerning their biological target and more homogeneous in their
      biochemical structure aiming at an improved benefit/risk ratio in the treatment
      of thrombotic disease. In this article, we will review the pharmacological
      characteristics of the new synthetic direct or antithrombin dependent inhibitors
      of FXa in the light of the modern concept of blood coagulation process. We will
      also present the most recent data from the clinical trials with synthetic
      inhibitors of FXa. Among them, the synthetic pentasaccharide fondaparinux is the
      first synthetic and specific FXa inhibitor, which has been approved by health
      authorities in Europe and in the USA for the prophylaxis of venous
      thromboembolism in major orthopaedic surgery and is being approved for the
      treatment of pulmonary embolism and DVT as a single daily subcutaneous injection.
      The phase II dose-finding trial of the "meta-pentasaccharide" idraparinux
      administered subcutaneously once weekly in the secondary prevention of VTE has
      been completed. DX-9065a is the first direct synthetic inhibitor which has been
      studied in patients with coronary disease. Razaxaban, BAY59-7939, ZK-807834 and
      JTV-803 are orally active direct FXa inhibitors, which have been studied in phase
      II trials. Several other synthetic direct inhibitors of FXa (such as FXV673,
      YM60828, KFA-1411) are in a pre-clinical stage of research. From a clinical point
      of view, the results of recent trials with the synthetic specific FXa inhibitors
      clearly show that the inhibition of FXa is a critical point in the antithrombotic
      strategy.

PMID- 16305518
TI  - Pharmacology and clinical potential of direct thrombin inhibitors.
AB  - Direct thrombin inhibitors represent a new class of anticoagulants that bind
      directly to thrombin and block the enzyme's interactions with its substrates.
      These agents have been developed, at least in part, to overcome the limitations
      of heparin and vitamin K antagonists. This paper (a) reviews why thrombin is an
      ideal target for new anticoagulants, (b) describes the pharmacological profiles
      of the various direct thrombin inhibitors, (c) outlines the potential mechanistic
      advantages of parenteral direct thrombin inhibitors over heparin, (d) defines the
      potential benefits of ximelagatran, the first orally active direct thrombin
      inhibitor, over vitamin K antagonists, and (e) provides clinical perspective on
      the strengths and weaknesses of the various parenteral and oral direct thrombin
      inhibitors.

PMID- 16305519
TI  - Direct thrombin inhibitors for the prevention of venous thromboembolism after
      major orthopaedic surgery.
AB  - Unfractionated heparin, low-molecular-weight heparins and vitamin K antagonists
      are established antithrombotic agents, but all have a number of limitations.
      Unfractionated heparin requires parenteral administration, has a short half-life
      and variable dose-response relationship. Low molecular weight heparins are more
      effective than low-fixed-dose unfractionated heparin in the prevention of
      postoperative venous thromboembolism in high-risk surgical patients but they
      still require subcutaneous administration. Vitamin K antagonists have a narrow
      therapeutic window and require a careful laboratory monitoring to minimize the
      risk of bleeding or thrombosis. Direct thrombin inhibitors are selective
      inhibitors of this key enzyme. Direct thrombin inhibitors inactivate thrombin
      without requiring any plasma cofactor, inhibit both free and fibrin-bound
      thrombin, and do not appreciably bind to plasma proteins. Ximelagatran, the first
      oral direct thrombin inhibitor, is rapidly absorbed and converted to its active
      form melagatran, which can itself be administered subcutaneously. Ximelagatran
      has been evaluated in the prevention of venous thromboembolism after major
      orthopaedic surgery, in the treatment of venous thromboembolism, in the
      prevention of stroke in patients with atrial fibrillation and in the prevention
      of recurrence after acute coronary syndromes. In the European studies in major
      orthopaedic surgery ximelagatran was administered orally after one or two days of
      melagatran, given subcutaneously. This review will report on the mechanism of
      action and clinical pharmacology of direct antithrombin agents and on the results
      of the clinical trials performed with direct thrombin inhibitors in the
      prevention of venous thromboembolism after major orthopaedic surgery. Taken
      together, these results indicate that direct thrombin inhibitors, ximelagatran in
      particular, have the potential to be a valid alternative to low molecular weight
      heparins and oral anticoagulants in the prevention of venous thromboembolism
      after major orthopaedic surgery.

PMID- 16305520
TI  - Safety and efficacy of ximelagatran: meta-analysis of the controlled randomized
      trials for the prophylaxis or treatment of venous thromboembolism.
AB  - BACKGROUND: Ximelagatran has been approved in Europe for VTE prophylaxis in
      orthopedic surgery at fixed doses and without laboratory monitoring. Aim of the
      study was to evaluate safety and efficacy of ximelagatran in a meta-analysis of
      prophylaxis and/or treatment randomized controlled trials. METHODS: Absolute risk
      of events for ximelagatran and OR for its comparison with LMWH and coumarins were
      calculated. Subgroup analysis was performed for ximelagatran regimen, comparator
      agent, type of surgery, starting time of prophylaxis. RESULTS: Twelve studies and
      16,992 patients were meta-analysed. Ximelagatran showed an absolute risk of major
      VTE of 4.04% and 1.69% and of major bleedings of 1.68% and 1.03% in prophylaxis
      and treatment trials, respectively. In prophylaxis trials, a significant excess
      mortality (OR: 2.5; 95% CI: 1.02 - 6.13) and an excess in major bleedings (OR:
      1.41; 95% CI: 0.93 - 2.14) was found in the whole ximelagatran group. No evidence
      of treatment effect for major VTE was seen in the comparison with LMWH (OR: 1.01;
      95% CI: 0.52 - 1.97). The cohort of patients treated with 24 mg b.i.d. showed
      similar results. An increase in the absolute risk of bleeding (from 1.04% to
      3.03%) was found between post and preoperative administration of ximelagatran.
      Major VTE risk was increased when ximelagatran was compared to b.i.d. LMWH.
      CONCLUSIONS: Ximelagatran can be considered for its potential advantages for
      prevention and treatment of VTE. Future efforts are needed by researchers to
      prospectively investigate the best postoperatively starting time and by
      clinicians to monitor overall mortality in prophylactic use.

PMID- 16305521
TI  - Direct thrombin inhibitors for the treatment of acute coronary syndromes and
      during percutaneous coronary interventions.
AB  - As acute coronary syndromes are principally sustained by plaque complication and
      subsequent thrombus formation, anticoagulant therapy plays a central role in
      avoiding ischemic events; its main targets are thrombin activity and generation.
      Despite its limitations, such as its scarce ability to activate bound thrombin
      and its unpredictable pharmacological response, heparin is the most widely used
      drug for this purpose. Direct thrombin inhibitors are biologically superior to
      heparin principally because they inhibit clot-bound and circulating thrombin
      without interacting with other plasma proteins. Their clinical role in acute
      coronary syndromes and during coronary intervention has been tested in several
      trials. This article overviews the principal trials involving active-site direct
      thrombin inhibitors in acute coronary syndrome and during coronary intervention
      and compares their efficacy and safety with unfractionated heparin. It also
      describes ongoing trials and analyzes further clinical developments such as their
      use in addition to the glycoprotein IIb/IIIa inhibitors and the potential
      advantage possible with new agents orally administered.

PMID- 16305522
TI  - Direct thrombin inhibitors for treatment of heparin induced thrombocytopenia,
      deep vein thrombosis and atrial fibrillation.
AB  - Thrombin is a central enzyme in hemostasis, exerting potent procoagulant effects
      and activating platelets. Recently, several small molecule direct thrombin
      inhibitors (DTI's) with important clinical applications have been developed. Both
      lepirudin and argatroban are effective in treatment of heparin-induced
      thrombocytopenia resulting in rapid normalization of platelet counts and a
      reduction in thrombotic events. Because of differences in clearance mechanisms,
      argatroban is preferable in patients with renal insufficiency and lepirudin if
      there is hepatic impairment. DTI's have also been evaluated in treatment of
      venous thromboembolism. Small studies with recombinant hirudin have shown
      promise. Ximelagatran is a new DTI in late-stage clinical trials with advantages
      for treatment of venous thromboembolism including oral administration and fixed
      dosing, making it convenient for long-term treatment. A Phase III trial
      demonstrated that ximelagatran was superior to placebo for preventing recurrent
      thrombosis in patients who had undergone six months of standard anticoagulant
      therapy for venous thromboembolism. Another large trial compared ximelagatran to
      standard treatment with enoxaparin and warfarin for treatment of symptomatic deep
      vein thrombosis in a Phase III trial of 2,528 patients. The results showed that
      ximelagatran administered twice daily was as effective as standard treatment in
      preventing recurrence with no increase in bleeding complications. Ximelagatran
      has also been evaluated in two Phase III trials in patients with atrial
      fibrillation. The primary analysis of both showed that ximelagatran was non
      inferior to warfarin for preventing stroke and other embolic events with no
      increase in bleeding complications. Unexpectedly, elevated serum transaminase
      levels were observed in 5-10% of patients receiving ximelagatran for over 1
      month, and routine monitoring may be necessary. The introduction of DTIs
      represents an important advance in treatment of heparin-induced thrombocytopenia.
      The oral direct thrombin inhibitor, ximelagatran, shows promise in providing
      simplified, effective therapy for venous thromboembolism and atrial fibrillation.

PMID- 16305523
TI  - Molecular mechanisms of and possible treatment strategies for idiopathic
      pulmonary fibrosis.
AB  - Pulmonary fibrosis is characterized by lung inflammation and abnormal tissue
      repair, resulting in the replacement of normal functional tissue with an abnormal
      accumulation of fibroblasts and deposition of collagen in the lung. This process
      involves cellular interactions via a complex cytokine-signaling mechanism and
      heightened collagen gene expression, ultimately resulting in its abnormal
      collagen deposition in the lung. Our current understanding of the pathogenesis of
      pulmonary fibrosis suggests that in addition to inflammatory cells, the
      fibroblast and signaling events that mediate fibroblast proliferation and
      myofibroblasts, play important roles in the diverse processes that constitute
      fibrosis. Increasing knowledge of cytokine biology, cytokine-signaling and cell
      matrix interactions have shed some light on the genesis of pulmonary fibrosis;
      however, the importance of inflammation in pulmonary fibrosis remains
      controversial. This remains true because the inflammatory component is variable
      at the time of diagnosis, and the most potent anti-inflammatory drugs that have
      been widely used in the treatment of pulmonary fibrosis do not seem to interfere
      with the fibrotic disease progression. Pulmonary fibrosis is a highly lethal
      disorder, which continues to pose major clinical challenges because an effective
      therapeutic regimen is yet to be determined. This review summarizes recent
      progress in understanding the molecular mechanisms of pulmonary fibrosis, and
      includes a more detailed discussion of the potential points of therapeutic attack
      in pulmonary fibrosis. In addition, a detailed discussion is presented regarding
      each of the potential therapies which have emerged from the animal models of
      pulmonary fibrosis, and which have been developed through advances in cellular
      and molecular biology.

PMID- 16305524
TI  - Cardiorenal consequences of atherosclerosis and statins therapy: from the past to
      the future.
AB  - Complications from atherosclerosis cause most deaths in western countries, and
      their incidence appears to be markedly increasing in developing countries, thus
      suggesting a correlation that is directly proportional to social progress. In
      recent years, the different branches of medical research, from studies on
      vascular disease to those on lipid and glucose metabolism, and also clinical
      research on coronary, carotid and peripheral artery diseases, epidemiologic and
      pharmacologic research, have concentrated on these diseases with the common aim
      of reducing the incidence of cardiovascular diseases, and mortality. Scientific
      progress has greatly improved our understanding of the pathogenic mechanisms
      underlying the progression of cardiovascular disease, and efforts in this
      discipline now appear more necessary than ever.

PMID- 16305526
TI  - Recent advances in antiviral nucleoside and nucleotide therapeutics.
AB  - Recent developments in nucleoside/nucleotide therapeutics and antiviral drug
      targets are described covering progress in the development of
      nucleoside/nucleotide mimetics for the treatment of influenza virus, human
      immunodeficiency virus type 1, hepatitis B and C virus, herpes virus infections;
      including herpes simplex virus, cytomegalovirus and varicella zoster virus
      infections, and the highly pathogenic poxviruses (variola, vaccinia and monkey
      pox) and filoviruses (Ebola and Marburg).

PMID- 16305527
TI  - Mitochondrial thymidine kinase inhibitors.
AB  - Mitochondrial thymidine kinase or TK-2 belongs to the family of mammalian
      deoxynucleoside kinases (dNKs) that catalyze the phosphorylation of
      deoxynucleosides to their corresponding deoxynucleoside monophosphates by gamma
      phosphoryl transfer of ATP. These enzymes are instrumental in the activation of
      deoxynucleoside analogues with biological and therapeutic properties. Moreover,
      dNKs are fundamental to maintain dNTPs pools for DNA synthesis and repair. TK-2
      has a mitochondrial localization and is the only thymidine kinase that is
      physiologically active in non-proliferating and resting cells. Several recent
      investigations point to an important role of TK-2 in the maintenance of
      mitochondrial dNTPs pools. Indeed, mutations in the gene encoding TK-2 have been
      associated with mitochondrial DNA (mtDNA) depletion that mostly affects skeletal
      muscle. Moreover, TK-2 has been suggested to be implicated in mitochondrial
      toxicity associated to prolonged treatments with nucleoside analogues (i.e AZT
      for the treatment of AIDS patients). In this scenario, TK-2 inhibitors could be a
      useful tool to further clarify both the physiological role of TK-2 in the
      maintenance of mitochondrial dNTP pools, and the possible contribution of TK-2 to
      the mitochondrial toxicity of pyrimidine nucleoside analogues. In the present
      article we review the most recent literature covering different aspects of TK-2
      as well as published TK-2 inhibitors, with special emphasis on acyclic nucleoside
      analogues that have been described by our research groups and whose prototype
      compound is 1-[(Z)-4-(triphenylmethoxy)-2-butenyl]thymine.

PMID- 16305528
TI  - MraY Inhibitors as Novel Antibacterial Agents.
AB  - MraY presents all necessary biological requirements to be considered as a target
      of interest for the discovery of novel antibacterials. Furthermore, several
      inhibitors aimed at this enzyme have been discovered. Amphomycin, which is
      currently used as a topical antibacterial in the veterinary industry is one of
      them, but the major source of future developments resides in the nucleoside based
      inhibitors group. This group has been subdivided into classes: Tunicamycins,
      Ribosamino-uridines, Uridylpeptides and Capuramycins. Analysis of pharmacological
      behaviours observed with several compounds within these classes, shows that broad
      spectrum antibacterial activity, including relevant resistant strains and in vivo
      efficacy without toxicity are achievable. Among them, Caprazamycins, Muraymycins,
      Riburamycins and Capuramycins present the most promising profiles.

PMID- 16305529
TI  - Transition states and inhibitors of the purine nucleoside phosphorylase family.
AB  - Purine nucleoside phosphorylase (PNP), an enzyme involved in the catabolism and
      recycling of nucleosides, is under investigation for the development of novel
      antibiotics. One method used for the design of inhibitors is transition state
      analysis. Chemically stable analogues of a transition state complex are predicted
      to convert the energy of enzymatic rate acceleration (kcat/k(non)) into binding
      energy. Transition state structures have been reported for the bovine (Bos
      taurus), human (Homo sapiens), and malarial (Plasmodium falciparum) PNPs. All
      three enzymes proceed through S(N)1-like mechanisms and have transition states
      with substantial ribooxocarbenium ion character. Bovine PNP proceeds through an
      early S(N)1-like transition state, whereas the human and malarial PNPs proceed
      through more dissociative transition state. Transition state analogues developed
      for PNP exhibit differential inhibition specificity for these three enzymes based
      upon their distinct reaction rates (kcat), mechanisms, and substrate specificity.
      The most powerful inhibitors of these three enzymes have picomolar dissociation
      constants, two of which are Immucillin-H and DADMe-Immucillin-H. MT-Immucillin-H
      was also developed as a specific inhibitor for P. falciparum PNP by virtue of its
      unique utilization of 5'-methylthio substrates. Although the transition state for
      tuberculosis (Mycobacterium tuberculosis) PNP is yet to be determined, inhibition
      values support a mechanism with a dissociative transition state like those of its
      human and plasmodial counterparts. Comparison of the transition states and
      substrate specificity of various PNPs permits the design of species-specific
      inhibitors for use as therapeutic agents.

PMID- 16305530
TI  - PNP anticancer gene therapy.
AB  - Escherichia coli purine nucleoside phosphorylase (PNP) catalyzes the cleavage of
      9-(2-deoxy-beta-D-ribofuranosyl)-6-methylpurine (MeP-dR), while human PNP does
      not. MeP-dR is well tolerated while the cleavage product, 6-methylpurine (MeP),
      is highly cytotoxic. This clinical profile suggests an anticancer gene therapy
      strategy in which solid tumors are transfected with the gene for E. coli PNP.
      Tumor cells expressing E. coli PNP will liberate MeP and be killed. Furthermore,
      MeP released from the cell via the purine transport system will enter nearby
      cells, resulting in bystander killing of tumor cells. To reduce toxicity
      resulting from activation of MeP-dR by intestinal tract flora, we redesigned the
      E. coli PNP active site to cleave prodrugs that are not cleaved by wild type E.
      coli PNP. It is possible that the variation of substrate specificity among
      enzymes that cleave nucleosides will have broader application in the gene therapy
      approach to prodrug activation. Here we review progress in the development of E.
      coli PNP anticancer gene therapy. We also review the structural basis for
      activity of nucleoside phosphorylases and suggest future directions for the
      development of activating enzymes for suicide gene therapy.

PMID- 16305533
TI  - Bioactive C-glycosides from bacterial secondary metabolism.
AB  - C-Glycosides are commonly regarded as unusual structures, but they are far more
      prevalent among natural products than is imagined. This review discusses the C
      glycosidic compounds produced by various bacteria, particularly the
      "biosynthetically talented" Streptomyces. The major structure types are
      presented, along with brief descriptions of the known biological and
      pharmacological properties of the compounds. Recent work has uncovered the
      genetic basis for the biosynthesis of several bacterial C-glycosides, and
      emphasis is placed on those cases where it has been possible to identify (at
      least provisionally) the C-glycosyltransferase in the pathway. Prospects for
      biosynthetic engineering, combinatorial biosynthesis, or glycorandomization in C
      glycosidic natural products are briefly discussed.

PMID- 16305531
TI  - Purine derivatives as ligands for A3 adenosine receptors.
AB  - Selective agonists and antagonists for A3 adenosine receptors (ARs) are being
      explored for the treatment of a variety of disorders, including brain and heart
      ischemic conditions, cancer, and rheumatoid arthritis. This review covers both
      the structure activity relationships of nucleoside agonist ligands and selected
      antagonists acting at this receptor and the routes of synthesis. Highly selective
      agonists have been designed, using both empirical approaches and a semi-rational
      approach based on molecular modeling. The prototypical A3 agonists IB-MECA 10 and
      the more receptor-subtype-selective Cl-IB-MECA 11, both of which have affinity in
      binding to the receptor of approximately 1 nM, have been used widely as
      pharmacological probes in the elucidation of the physiological role of this
      receptor. In addition to the exploration of the effects of structural
      modification of the adenine and ribose moieties on A3AR affinity, the effects of
      these structural changes on the intrinsic efficacy have also been studied in a
      systematic fashion. Key structural features determining A3AR interaction include
      the N6-benzyl group, 2-position substitution such as halo, substitution of ribose
      (e.g., the (N)-methanocarba ring system, various 2'- and 3'-substitutions and 4'
      thio substitution of oxygen). Conformational studies of the ribose moiety and its
      equivalents indicate that the ring oxygen is not required and the North (N) ring
      conformation is preferred in binding to the A3AR. Using these observations, a
      series of ring constrained (N)-methanocarba 5'-uronamide derivatives was recently
      reported to be highly selective A3AR agonists, the most notable amongst them was
      MRS3558 113 having a Ki value in binding to the human A3 receptor of 0.3 nM.

PMID- 16305534
TI  - Recent advances in aryl C-glycoside synthesis.
AB  - Aryl C-glycosides are stable analogs of the corresponding O-glycosides. Because
      of their favorable pharmacological profiles attributed primarily to the C
      glycosyl moiety, aryl C-glycosides have gained increasing popularity as drug
      candidates. In this review we focus on the synthesis of aryl C-glycosides
      including puerarin and kendomycin. This review is organized based on the type of
      chemistry used in the assembly of the C-glycosides with the following sub
      sections: electrophilic reaction, cross-coupling reaction, free radical reaction,
      cyclization, intramolecular O-C rearrangement, umpolung, and miscellaneous
      reactions.

PMID- 16305535
TI  - Recent advances in the synthesis of C-linked glycoconjugates.
AB  - During the last five years, the scientific community has seen a dramatic increase
      in the number of synthetic methods or strategies to prepare C-linked
      glycoconjugates. One reason for this increase is that the biological significance
      and roles of many O- and N-linked glyconconjugates has become evident. This
      review will summarize the biological importance of glycoconjugates and outline
      recent advances in the preparation of C-linked glycoconjugates that have appeared
      in the literature since the new millennium.

PMID- 16305536
TI  - C-glycosides and aza-C-glycosides as potential glycosidase and
      glycosyltransferase inhibitors.
AB  - Glycosylation as one of most important post-translational modification of gene
      products is often critical to specific cellular biological functions. Since
      elevated glycoprocessing enzyme activities have been implicated in the
      development of various diseases including cancer metastasis, glycosidases and
      glycosyltransferases are considered as therapeutic targets. Azasugars, the first
      generation of enzyme inhibitors, have been extensively investigated and two
      azasugar-based drugs (Miglitol and Miglustat) have been approved. Aza-C
      glycosides, molecules with an azasugar core and various C-aglycons attached at
      the pseudo anomeric center, have the potential to become the second-generation
      inhibitors with improved specificity and membrane permeability. In this review, C
      glycosides, aza-C-glycosides, and aza-C-disaccharides are introduced as
      glycoprocessing enzyme inhibitors. The synthetic approaches toward those
      molecules are described based on the key reactions, which include reductive
      amination, nucleophilic ring opening of epoxides, nucleophilic addition to imines
      (C=N), and hetero-Michael additions. Aza-C-glycoside-based libraries are also
      described for the discovery of promising second-generation inhibitors.

PMID- 16305537
TI  - Recent advances in the synthesis of C-oligosaccharides.
AB  - This paper reviews the recent advances in the synthesis of catabolically stable
      sugar mimetics, C-oligosaccharides. These compounds are synthetic analogs of the
      naturally occurring O-oligosaccharides, in which the interglycosidic oxygen has
      been replaced by a methylene group. This review is organized in terms of
      chemistry used to assemble C-oligosaccarides under the sub-headings: anionic
      approaches, cationic methods, reductive glycosyl samarium chemistry, cyclization
      methodology, and free radical chemistry.

PMID- 16305538
TI  - exo-Glycal chemistry: general aspects and synthetic applications for biochemical
      use.
AB  - It is well known that carbohydrates play an indispensable role in a variety of
      essential biological activities, such as cell-cell adhesion, bacteria and virus
      infections, and tumor metastasis. Among an increasing number of sugars and sugar
      mimetics that have been designed and synthesized for the purpose of drug
      discovery, C-glycosides are considered to be one of the best choices on account
      of their stability and resemblance as they differ from normal glycosides only in
      glycosidic linkages. exo-Glycals are unsaturated sugars that have a double bond
      attached to the anomeric center outside the sugar ring. These carbohydrate
      molecules are useful for the synthesis of C-glycosides and compounds containing
      quaternary carbons, provided that the olefin can be properly reduced or
      functionalized. This review places special emphasis on two aspects of exo-glycals
      including general methods of preparation and synthetic applications for making
      biologically important molecules. The first half discusses the methods of
      addition/elimination and Ramburg-Backlund rearrangement that offer many
      beneficial features including a wide range of double bond substitutions, limited
      reaction steps, easy operation and good overall yields. The rest of the article
      demonstrates a number of synthetic studies using exo-glycals as the starting
      materials. The target molecules can be categorized into three groups, namely C
      glycosides, enzyme inhibitors and bioactive natural products.

PMID- 16305540
TI  - Synthesis of proteins by native chemical ligation using Fmoc-based chemistry.
AB  - C-terminal peptide alpha-thioesters are valuable intermediates in the
      synthesis/semisynthesis of proteins by native chemical ligation. They are
      prepared either by solid-phase peptide synthesis (SPPS) or biosynthetically by
      protein splicing techniques. The present paper reviews the different methods
      available for the chemical synthesis of peptide alpha-thioesters using Fmoc-based
      SPPS.

PMID- 16305541
TI  - Chemical synthesis of proteins and circular peptides using Nalpha-(1-phenyl-2
      mercaptoethyl) auxiliaries.
AB  - An overview of the applications of Nalpha-(1-phenyl-2-mercaptoethyl) auxiliary is
      presented. We describe the on resin preparation (Calpha-carboxy and thioester) of
      Nalpha-auxiliary derivatives of glycine and the synthesis and incorporation of
      preformed Nalpha-auxiliary derivatives of glycine and alanine with the protection
      schemes, including the thiazolidine strategy for SPPS. Such approaches allowed
      the synthesis of the protein cytochrome b562 as well as native circular peptides
      after successful removal of the auxiliary.

PMID- 16305542
TI  - Chemical synthesis approaches to the engineering of ion channels.
AB  - Chemoselective ligation strategies have previously provided synthetic access to
      water-soluble proteins with novel properties, and more recently these strategies
      have been used to prepare ion channels. Examples of ion channels prepared by
      total chemical synthesis include bacterial mechanosensitive channels, and viral
      ion channels. Chemical protein synthesis allows for the generation of ion channel
      proteins with both native, and engineered structural or conductance properties.

PMID- 16305543
TI  - Mimicking reverse protein splicing by three-segment tandem peptide ligation.
AB  - Here we report a bi-directional and interchangeable three-segment peptide
      ligation of N, M, and C-segments, mimicking the reverse process of protein
      splicing to form, in tandem, a tripartite NMC-peptide using a synthetic intein, a
      role served by the M-segment with an N-terminal Ser or Thr and a C-terminal
      thioester.

PMID- 16305544
TI  - The mechanism of intein-mediated protein splicing: variations on a theme.
AB  - Intein-mediated protein splicing is facilitated by four separate but coordinated
      nucleophilic displacement reactions that result in the excision of the intein and
      the ligation of the flanking polypeptides, called the exteins. These reactions
      are catalyzed by the intein plus the first downstream extein amino acid without
      the assistance of cofactors or auxiliary enzymes. Non-canonical inteins missing
      conserved nucleophilic residues at the N- or C-terminus likely splice using
      variations of the standard mechanism.

PMID- 16305545
TI  - Incorporation of selenocysteine into proteins using peptide ligation.
AB  - Expressed protein ligation has become a frequently used technique to insert non
      standard amino acids into proteins. The technique has been adapted to insert
      selenocysteine residues in place of cysteine residue in proteins, taking
      advantage of the similarity in the chemistries of sulfur and selenium. This
      replacement can confer unique structural and catalytic properties to enzymes and
      proteins. The development of this technique also allows for naturally occurring
      selenoproteins to be produced semisynthetically.

PMID- 16305546
TI  - Protein chemical ligation as an invaluable tool for structural NMR.
AB  - This article reviews the methodology and recent applications of expressed protein
      ligation for NMR structural studies of proteins and protein complexes.

PMID- 16305547
TI  - Intein-mediated, in vitro and in vivo protein modifications with small molecules.
AB  - We review intein-mediated approaches for the site-specific modifications of
      proteins and highlight their applications in (1) the site-specific in vitro and
      in vivo biotinylation of proteins for protein arrays and (2) the site-specific in
      vivo labeling of proteins in living cells.

PMID- 16305548
TI  - Expressed protein ligation to obtain selectively modified aldo/keto reductases.
AB  - Specific enzyme immobilization has moved into the focus for many applications in
      biochemical research fields. Expressed Protein Ligation (EPL) has been proven to
      be ideal to selectively label proteins at single positions. Applying this
      technique to enzymes of the aldo/keto reductase superfamily provides a new
      approach to generate native or modified redox enzymes for direct and indirect
      immobilization.

PMID- 16305549
TI  - Expressed protein ligation to study protein interactions: semi-synthesis of the G
      protein alpha subunit.
AB  - Interactions between G proteins and GPCRs are fundamental for transmitting
      signals for a multitude of physiologic responses. Little is known regarding the
      protein-protein interface between the G protein and the receptor, much less the
      mechanisms for receptor activation of G proteins. Here, we will describe how
      expressed protein ligation will aid in the study of protein-protein interactions
      between semi-synthetic G alpha subunits and GPCRs.

PMID- 16305550
TI  - Expressed protein ligation: a new tool for the biosynthesis of cyclic
      polypeptides.
AB  - The present paper reviews the use of expressed protein ligation for the
      biosynthesis of backbone cyclized polypeptides. This general method allows the in
      vivo and in vitro biosynthesis of cyclic polypeptides using recombinant DNA
      expression techniques. Biosynthetic access to backbone cyclic peptides opens the
      possibility to generate cell-based combinatorial libraries that can be screened
      inside living cells for their ability to attenuate or inhibit cellular processes.

PMID- 16305551
TI  - Using siclopps for the discovery of novel antimicrobial peptides and their
      targets.
AB  - High throughput screening of SICLOPPS libraries afforded six distinct cyclic
      peptides that inhibit Escherichia coli growth both in liquid and solid media. One
      of these peptides (LN05) reduced both bacterial growth rate and caused cell
      aggregation in liquid media. Mutant bacteria immune to LN05 action were obtained
      at a frequency of 10(-7). Over-expression of an E. coli genomic library in the
      presence of LN05 production resulted in enrichment of a single genomic construct,
      a fragment of the NarZ gene.

PMID- 16305552
TI  - Unusual solute protection against pressure inactivation of yeast alcohol
      dehydrogenase.
AB  - A 3:1 combination of sucrose and glycine provides significantly greater
      protection against pressure-induced inactivation of yeast alcohol dehydrogenase
      than either solute alone. Trehalose, alone, gives much greater protection than
      sucrose alone, but not so in combination with glycine. These are striking new
      findings that cannot be accounted for by current theories of protein
      stabilization.

PMID- 16305553
TI  - Prediction of protein secondary structure using improved two-level neural network
      architecture.
AB  - In this paper we propose constructing an improved two-level neural network to
      predict protein secondary structure. Firstly, we code the whole protein
      composition information as the inputs to the first-level network besides the
      evolutionary information. Secondly, we calculate the reliability score for each
      residue position based on the output of the first-level network, and the role of
      the second-level network is to take full advantage of the residues with a higher
      reliability score to impact the neighboring residues with a lower one for
      improving the whole prediction accuracy. Thirdly, considering it is indeed a
      problem that the target protein can be lost in the multiple sequence alignment we
      propose to code single sequence into the second-level network. The experimental
      results show that our proposed method can efficiently improve the prediction
      accuracy.

PMID- 16305554
TI  - Proteome analysis of Nelore bull (Bos taurus indicus) seminal plasma.
AB  - The Nelore bull (Bos taurus indicus) seminal plasma proteome was analyzed by
      MALDI-TOF MS and two-dimensional gel electrophoresis. A total of 260 spots were
      visualized in the 2-DE gel (pI range 3-10) and 13 spots could be identified by
      peptide mass fingerprinting corresponding to 11 different polypeptides. The
      results allowed the creation of the first proteomic map of Bos taurus indicus
      seminal plasma. The roles of the identified proteins in the bull seminal plasma
      are discussed.

PMID- 16305556
TI  - Purification and preliminary crystallographic studies of CutC, a novel copper
      homeostasis protein from Shigella flexneri.
AB  - CutC is a novel copper homeostasis protein containing 248 amino acids. Here we
      report the cloning, expression, purification, crystallization and preliminary X
      ray crystallographic studies of CutC from Shigella flexneri 2a. Purification of
      CutC and its selenomethionine (SeMet) derivate were done using immobilized metal
      ion affinity chromatography, size-exclusion and ion-exchange chromatography. The
      purified proteins were crystallized using the hanging drop vapor diffusion
      method. The diffraction data for the native and SeMet CutC, respectively, have
      been collected with resolution of 1.7 A and 2.1 A. They belong to the space group
      C2221 and similar cell dimension. The native protein crystals have cell
      parameters: a=75.3267, b=97.6718, c=132.6910.

PMID- 16305555
TI  - Crystallization and preliminary X-ray diffraction studies of two myotoxic Lys49
      phospholipases A2 complexed with alpha-tocopherol.
AB  - BnSP-7 and BnSP-6, two Lys49-phospholipase A2 isolated from Bothrops neuwiedi
      pauloensis snake venom, were co-crystallized with alpha-tocopherol and X-ray
      diffraction data were collected for both complexes (2.2 and 2.6 A). A new
      "alternative" quaternary conformation for these two complexes compared with all
      other dimeric Lys49-PLA2 has been observed.

PMID- 16305559
TI  - Registering protocols for systematic reviews with BJOG.

PMID- 16305560
TI  - Assisted reproduction technology and defects of genomic imprinting.
AB  - It is estimated that approximately 1% of the newborn population of the British
      Isles are conceived following assisted reproduction technologies such as in vitro
      fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). While the long
      term outcome of IVF children is mostly reassuring, some concerns remain.
      Specifically, recent studies have suggested a possible association between
      assisted conception and clinical conditions of genetic origin known as genomic
      imprinting defects. This has arisen from several different studies observing an
      excess of assisted conceptions among the rare clinical disorders of Beckwith
      Wiedemann syndrome (BWS) and Angelman syndrome (AS). The numbers of such patients
      described in the studies to date are small but indicate a clear need for large
      scale investigations to clarify the link between genomic imprinting defects and
      assisted conception as well as to establish the exact biological basis of any
      such link. In view of the strong public interest in this area of medicine, it
      behoves all professionals working in reproductive medicine and associated areas
      to be aware of these emerging data and be in a position to discuss them in as
      informed and responsible a manner with patients, as current data limitations
      permit.

PMID- 16305561
TI  - Prognostic value of the labour admission test and its effectiveness compared with
      auscultation only: a systematic review.
AB  - OBJECTIVE: To assess the effectiveness of the labour admission test in preventing
      adverse outcomes, compared with auscultation only, and to assess the test's
      prognostic value in predicting adverse outcomes. DESIGN: Systematic review.
      SETTING: Labour wards in hospitals. POPULATION: Pregnant women in labour. Three
      randomised controlled trials including 11,259 women and 11 observational studies
      including 5831 women. METHODS: Literature searches in Medline, EMBASE, CINAHL,
      SweMed, The Cochrane Central Register of Controlled Trials, reference lists from
      identified studies and contact with experts. MAIN OUTCOME MEASURES: Obstetric
      interventions (augmentation of labour, continuous electronic fetal monitoring,
      epidural analgesia, fetal blood sampling and operative deliveries) and neonatal
      outcomes (perinatal mortality, Apgar score, seizures, resuscitation and admission
      to neonatal unit). RESULTS: Meta-analyses of the controlled trials found that
      women randomised to the labour admission test were more likely to have minor
      obstetric interventions like epidural analgesia [relative risk (RR) 1.2, 95%
      confidence interval (95% CI) 1.1-1.4], continuous electronic fetal monitoring (RR
      1.3, 95% CI 1.2-1.5) and fetal blood sampling (RR 1.3, 95% CI 1.1-1.5) compared
      with women randomised to auscultation on admission. There were no significant
      differences in any of the other outcomes. From the observational studies,
      prognostic value for various outcomes was found to be generally poor. Likelihood
      ratio (LR) for a positive test was above 10 in 2 of 28 single outcomes and
      between 5 and 10 in six outcomes. CONCLUSIONS: There is no evidence supporting
      that the labour admission test is beneficial in low risk women.

PMID- 16305562
TI  - The development and process evaluation of an information-based intervention for
      pregnant women aimed at addressing rates of caesarean section.
AB  - OBJECTIVE: Few strategies aimed at addressing rising rates of caesarean section
      have explicitly involved information-based approaches for pregnant women. This
      study describes the development and evaluation of such an intervention for
      pregnant women, encompassing pamphlets and a peer support network (PSN). DESIGN:
      Process evaluation. SETTING: The study was undertaken at a metropolitan teaching
      hospital in Adelaide, South Australia. POPULATION: A consecutive sample of
      pregnant women attending the ultrasound clinic over a two-month period, recruited
      at 18 weeks of gestation. METHODS: Participants received two pamphlets at 18
      weeks of gestation and information on a PSN at around 28 weeks of gestation. A
      questionnaire was sent to women at seven weeks postnatal, asking them to evaluate
      the intervention. MAIN OUTCOME MEASURES: The extent to which the intervention
      resources were used and participants were satisfied with the resources they
      received. RESULTS: Ninety-two women returned questionnaires (response rate of
      62%). Women generally resisted engaging with the informational resources, citing
      irrelevance to their situation, for example, 53% (49/92) read all of the
      pamphlets. None of the women used the PSN. Women who had experienced childbirth
      previously and those of higher education were significantly more likely to read
      the pamphlets. While generally satisfied with pamphlet content, one in five women
      reported feeling distressed by some of the information. CONCLUSIONS: This
      exploratory study casts doubt on the notion of information provision for pregnant
      women as a panacea for addressing rising rates of caesarean section.

PMID- 16305563
TI  - Intracervical application of the nitric oxide donor isosorbide dinitrate for
      induction of cervical ripening: a randomised controlled trial to determine
      clinical efficacy and safety prior to first trimester surgical evacuation of
      retained products of conception.
AB  - OBJECTIVE: To determine the therapeutic efficacy and safety of a nitric oxide
      (NO) isosorbide dinitrate donor to induce cervical ripening of women with missed
      abortions before surgical evacuation of the uterus. DESIGN: A prospective,
      randomised, double-blind controlled trial. SETTING: Tertiary referral maternity
      teaching hospital. Population Sixty women with missed abortions and no cervical
      dilation. METHODS: Women requesting surgical evacuation of the uterus were
      randomly selected to receive endocervical 80 mg/1.5 mL isosorbide dinitrate gel
      solution (n= 30) or 400 mug/1.5 mL misoprostol gel solution (n= 30) every 3 hours
      to a maximum of four doses or until reaching cervical ripening. Vital signs and
      symptoms were recorded at baseline and then every 3 hours until finishing
      therapy. Adverse events, such as headache, abdominal pain, pelvic pain, backache,
      nausea and vomiting, were evaluated. MAIN OUTCOME MEASURES: Probability of
      reaching cervical ripening >8 mm Hegar dilator; evaluated at 3, 6, 9 and 12 hours
      after application of isosorbide dinitrate or misoprostol. RESULTS: The
      probabilities of induction of cervical ripening by isosorbide dinitrate and
      misoprostol after four repeated doses at 3-hour intervals were significantly
      different (P<0.001). Efficacy of therapy after 12 hours was 97% for the
      isosorbide dinitrate group and 70% for the misoprostol group. Systolic and
      diastolic blood pressures were lower after administration of isosorbide dinitrate
      than prostaglandin analogues. The difference in the mean systolic and diastolic
      blood pressure between treatment groups was greatest at 3 hours, with a
      difference of 7.7 mmHg (P<0.001) and 5.9 mmHg (P<0.003), respectively. The most
      frequent side effect associated with isosorbide dinitrate administration was
      headache, which occurred in 18 out of 30 patients, compared with only 5 out of 30
      women in the misoprostol group [relative risk (RR) 2.41, 95% confidence interval
      (CI) 1.45-4.03, P<0.001). Women treated with misoprostol reported mainly pelvic
      pain (RR 3.24, 95% CI 1.99-5.27, P<0.001). CONCLUSIONS: Intracervical
      administration of 80 mg isosorbide dinitrate in women with missed abortions
      appears to be effective for cervical ripening prior to surgical evacuation of the
      uterus. Differences in the incidence of non-serious adverse events are not likely
      to be clinically significant.

PMID- 16305564
TI  - Epstein-Barr virus infection during pregnancy and the risk of adverse pregnancy
      outcome.
AB  - OBJECTIVES: To study the association between Epstein-Barr virus (EBV) antibody
      status in early pregnancy and pregnancy outcomes including fetal death, length of
      gestation and fetal weight and length at birth. DESIGN: Nested control study.
      SETTING: Population based health registers. POPULATION: The source population
      comprised 35,940 pregnant women. Cases were all (280) women with fetal death and
      a random sample of 940 women with a live born child. METHOD: Information on
      pregnancy outcome was obtained from the Norwegian Medical Birth Registry. Serum
      samples from the first trimester were tested for EBV antibodies. In women
      seronegative for EBV, further serum from late pregnancy was analysed to detect
      seroconversion. Main outcome measures Vital status, length of gestation, weight
      and length at birth. RESULTS: There was no association between EBV antibody
      status and fetal death. Women with significant EBV reactivation had a
      significantly shorter duration of pregnancy, and associated lighter babies,
      compared with women without significant reactivation (stillborn: 176 vs 197 days,
      P=0.16, and live born: 271 vs 279 days, P=0.03, respectively). CONCLUSION:
      Significant reactivation of EBV infection during pregnancy may influence
      pregnancy duration.

PMID- 16305565
TI  - United kingdom amniotic fluid embolism register.
AB  - OBJECTIVE: The United Kingdom Amniotic Fluid Embolism Register was established to
      identify the incidence of the condition and examine any differences or common
      factors between survivors and fatalities. DESIGN: An anonymous voluntary
      register. SETTING: The United Kingdom from 1997 to 2004. POPULATION: Any woman
      with a clinical diagnosis of amniotic fluid embolism. The entry criteria were as
      follows: acute hypotension or cardiac arrest, acute hypoxia and coagulopathy with
      onset during labour, caesarean section or within 30 minutes of delivery with no
      other clinical condition or potential explanation for the symptoms and signs.
      METHODS: A data collection form was completed after reporting. MAIN OUTCOME
      MEASURES: Mortality and morbidity rates in women and their babies. RESULTS: Of 66
      cases, 44 had sufficient information to be included. Thirteen (29.5%; 95% CI 17
      45%) women died. If the five extra deaths in the Confidential Enquiry into
      Maternal Death were included, the mortality would be 37% (95% CI 23-52%). Of the
      31 survivors, 12 women had a cardiac arrest, 7 had a hysterectomy, 2 had further
      laparotomies, 1 had subglottic stenosis and 2 had persisting neurological
      impairment. Twenty-four of the 31 survivors were admitted to intensive care
      units. Of the 13 women who died, 7 of their babies survived. Four were acidotic
      at birth, of whom two developed hypoxic ischaemic encephalopathy (HIE) and one of
      these is known to have developed cerebral palsy. In 18 cases, the woman survived
      and the baby was alive and in utero at the time of the maternal collapse. Four of
      these died, four had HIE with one known to have developed cerebral palsy and one
      other was acidotic at birth. CONCLUSION: The mortality of amniotic fluid embolism
      is high but the majority of women will survive. There is significant maternal and
      neonatal morbidity even when the woman survives. Continuing assessment of cases
      of amniotic fluid embolism is important to identify ways of improving outcome.

PMID- 16305566
TI  - Survival after non-aggressive obstetric management in cases of severe fetal
      anomalies: a retrospective study.
AB  - OBJECTIVE: Obstetricians may choose to refrain from interventions aimed at
      sustaining fetal life (i.e., non-aggressive obstetric management) when the fetus
      has an extremely poor prognosis. However, if the infant is then born alive,
      crucial neonatal management decisions then have to be made. We sought empirical
      data concerning such perinatal end-of-life decisions. Firstly, to describe
      survival during delivery and after birth following non-aggressive obstetric
      management, and secondly, to describe neonatal management in infants born alive
      after non-aggressive obstetric management. DESIGN: Retrospective descriptive
      study. SETTING: Tertiary centre. POPULATION: Eighty-one infants born to women who
      opted for a non-aggressive obstetric management policy because of sonographically
      diagnosed severe fetal anomaly. METHODS: Data were collected from obstetric and
      neonatal records, as well as ultrasound reports. MAIN OUTCOME MEASURES: Survival,
      neonatal management and health status after birth. RESULTS: Relevant data were
      available for 78/80 (98%) infants. Six (8%) infants died in utero, 16 (21%) died
      during delivery (11 from cephalocentesis) and 56 (72%) were born alive. Life
      sustaining neonatal treatment was initiated in 29 (52%) of the live-born infants.
      Twenty-three of these 29 (79%) infants died within six months of birth. Of the 27
      live-born infants who did not receive neonatal life-sustaining treatment, 25
      (93%) died. Eight infants survived; all with severe health problems. CONCLUSION:
      Life-sustaining neonatal support after non-aggressive obstetric management in the
      presence of severe fetal malformation has little impact on survival.

PMID- 16305567
TI  - Changes in gustatory function during the course of pregnancy and postpartum.
AB  - OBJECTIVE: To investigate changes in gustatory function during pregnancy and
      postpartum. DESIGN: Prospective study. SETTING: Obstetric outpatient clinic,
      Zurich University Hospital. POPULATION: Forty-four pregnant women, 46 controls.
      METHODS: A threshold-like measure of gustatory function was obtained for
      different concentrations of the four basic tastes using 'taste tablets'; subjects
      were also asked to rate the intensity and pleasantness/unpleasantness of
      suprathreshold taste solutions. Tests were performed in early pregnancy up to 14
      weeks of gestational age, 8-12 weeks after the first and second examination and
      at least 6 weeks after birth. In parallel, controls were tested four times at
      intervals of 8-12 weeks. MAIN OUTCOME MEASURES: Gustatory score (number of
      correctly identified tastes). Results Pregnant subjects exhibited a decreased
      gustatory function compared with non-pregnant controls, still being present after
      birth. These 'objective' changes were observed although pregnant women rated the
      intensity of suprathreshold taste stimuli not significantly different from
      controls. Pregnant women rated salty stimuli to be more pleasant during the
      second trimester while they rated the salty stimuli to be less pleasant during
      the first and third trimester, and after birth. CONCLUSIONS: Pregnancy is
      accompanied by changes in gustatory function. Decreased gustatory sensitivity may
      allow pregnant and breastfeeding women to vary their diet in order to consume
      adequate electrolytes. The discrepancy between 'objective' and 'subjective'
      findings in gustatory function may relate to changes in central processing of
      gustatory information during pregnancy.

PMID- 16305568
TI  - Recurrence risk in hyperemesis gravidarum.
AB  - OBJECTIVES: To compare the risk of hyperemesis gravidarum in second pregnancies
      in women with and without hyperemesis in their first pregnancy, and to determine
      if this risk changes with changes in paternity or with the interval between
      deliveries. DESIGN: Cohort study. SETTING: Data from the population-based Medical
      Birth Registry of Norway, 1967-1998. Sample All women in the registry with
      records of their first and second singleton delivery, a total of 547,238 women.
      METHODS: The relative risk of hyperemesis in the second delivery was estimated as
      odds ratios (ORs) in logistic regression models, controlling for potential
      confounding factors. MAIN OUTCOME MEASURES: The main outcome measure was the risk
      of hyperemesis in the second pregnancy according to hyperemesis in the first
      pregnancy, interval between deliveries and change in paternity. RESULTS: The risk
      of hyperemesis was 15.2% in the second pregnancy in women with and 0.7% in women
      without previous hyperemesis [OR=26.4, 95% confidence interval (CI) 24.2, 28.7].
      The OR did not change after adjustment for maternal age, change in paternity,
      period of the first delivery and time interval between deliveries. After a change
      in paternity, the risk of recurrent hyperemesis was 10.9% compared with 16.0% in
      women without a change in paternity [adjusted OR (aOR)=0.60, 95% CI 0.39, 0.92].
      The risk of hyperemesis in the second pregnancy increased with increasing time
      interval between deliveries, but only in women with no previous hyperemesis.
      CONCLUSIONS: The primary finding was the high risk of recurrence observed in
      women with hyperemesis in the first pregnancy. The risk was reduced by a change
      in paternity. For women with no previous hyperemesis, a long interval between
      births slightly increased the risk of hyperemesis in the second pregnancy.
      Further studies are needed to explore the relative impact of genetic and
      environmental factors and their possible interactions in hyperemesis gravidarum.

PMID- 16305569
TI  - Mode of delivery and severe stress incontinence. a cross-sectional study among
      2,625 perimenopausal women.
AB  - OBJECTIVE: To estimate the prevalence of severe stress urinary incontinence (SUI)
      among perimenopausal women and to examine potential obstetric risk factors.
      DESIGN: Mail survey of female volunteers for epidemiological research. SETTING:
      Postal questionnaire on SUI. POPULATION: Three thousand one hundred and fourteen
      women aged 49-61 years who comprised the GAZEL cohort. METHODS: Logistic
      regression using data from the entire cohort to estimate the impact of risk
      factors. A second logistic regression using data from women who had given birth
      included obstetric history. MAIN OUTCOME MEASURE: Prevalence of severe SUI
      defined by the response 'often' or 'all the time' to the question 'Does urine
      leak when you are physically active, cough or sneeze?' RESULTS: Two thousand six
      hundred and twenty-five women (85%) completed and returned the questionnaire The
      frequency of SUI reported in the preceding four weeks was as follows: 'never'
      32%, 'occasionally' 28%, 'sometimes' 26%, 'often' 10% and 'all the time' 5%.
      Prevalence of severe SUI was lowest among nulliparous women (7%), but it was
      similar among parous women regardless of birth number (14-17%). The prevalence of
      severe SUI was not associated with mode of delivery (14% for women delivered by
      caesarean only vs 16% for vaginal births). Significant risk factors for severe
      SUI were high body mass index (BMI >30), diabetes mellitus, previous incontinence
      surgery, parity and first delivery under the age of 22 years. CONCLUSION:
      Previous pregnancy itself is a risk factor for severe SUI among women who reach
      the age of 50. In this age group the impact of the mode of delivery (spontaneous,
      forceps or caesarean) on severe SUI is slight.

PMID- 16305571
TI  - Vulvar siliconoma migrating from injected silicone breast augmentation.

PMID- 16305570
TI  - A randomised controlled trial to evaluate the effect of self-administered
      analgesia on women's experience of outpatient treatment at colposcopy.
AB  - OBJECTIVE: To evaluate the effect of self-administered isoflurane and desflurane
      on women's experience of outpatient treatment at colposcopy. DESIGN: A
      prospective double-blinded randomised controlled trial. SETTING: A colposcopy
      clinic serving a regional population. POPULATION: Three hundred and ninety-six
      women scheduled for treatment of cervical intraepithelial neoplasia (CIN) by
      large loop excision of the transformation zone (LLETZ). METHODS: Self
      administration of trial gas during a LLETZ procedure. One hundred and ninety
      eight women were randomised to use isoflurane and desflurane and 198 to use
      placebo. MAIN OUTCOME MEASURES: Patient satisfaction, pain and anxiety. RESULTS:
      The mean pain score for cervical surgery was significantly lower for women using
      isoflurane and desflurane (22.4) than the placebo arm (29.6) (P= 0.003). There
      was no significant difference between arms in anxiety levels before or after
      treatment. More women using isoflurane and desflurane (78%) reported 'total
      helpfulness' of the trial gas than those using placebo (67%) (P= 0.012). A
      subgroup analysis of trial participants classified as anxious by Hospital Anxiety
      and Depression Scale (HADS) score at recruitment showed that using isoflurane and
      desflurane significantly increased total treatment acceptability, helpfulness of
      the gas and willingness to undergo a similar procedure at six-month follow up.
      CONCLUSION: Satisfaction with outpatient treatment at colposcopy is generally
      high. The main effect of isoflurane and desflurane evaluated in this trial was to
      reduce pain. It appeared to be effective for women with clinically significant
      anxiety and could be offered as an alternative to general anaesthesia.

PMID- 16305572
TI  - Recurrent vaginal erosion of tension free vaginal tape due to Actinomyces
      infection.

PMID- 16305573
TI  - Progress of first stage of labour for multiparous women: an observational study.
AB  - As there is no universal definition of 'normal' labour, diagnosing prolonged
      labour is inherently difficult. Simple charts (partograms) are used to aid this
      process; however, there are little empirical data on which to base such charts.
      Therefore, we monitored 403 multiparous women, in the first stage of labour with
      uncomplicated term pregnancies, in a midwife-led unit. They had vaginal
      examinations every 2 hours, and we modelled rates of cervical dilatation for all
      women, either to the end of the first stage of labour or to the point of transfer
      for intervention. Overall, the median rate of dilatation was 1.9 cm/hour and the
      5th percentile was 0.5 cm/hour. There was a weak positive correlation between
      initial dilatation and rate of dilatation (r= 0.2). Individualised computer-based
      partograms incorporating some of the factors that affect progress might prove
      useful in the future.

PMID- 16305574
TI  - Transcervical cell sampling: a need for clear terminology.

PMID- 16305575
TI  - Misoprostol in obstetrics.

PMID- 16305577
TI  - 'Conception origin'versus'ambient outdoor temperature throughout pregnancy' in
      relation to offspring birthweight.

PMID- 16305580
TI  - Uterine rupture after induction of labour in women with previous caesarean
      section.

PMID- 16305581
TI  - Physiologically based pharmacokinetic modelling: a sound mechanistic basis is
      needed.

PMID- 16305582
TI  - Physiologically based pharmacokinetic modelling of the three-step metabolism of
      pyrimidine using C-uracil as an in vivo probe.
AB  - AIMS: Approximately 80% of uracil is excreted as beta-alanine, ammonia and CO2
      via three sequential reactions. The activity of the first enzyme in this scheme,
      dihydropyrimidine dehydrogenase (DPD), is reported to be the key determinant of
      the cytotoxicity and side-effects of 5-fluorouracil. The aim of the present study
      was to re-evaluate the pharmacokinetics of uracil and its metabolites using a
      sensitive assay and based on a newly developed, physiologically based
      pharmacokinetic (PBPK) model. METHODS: [2-(13)C]Uracil was orally administrated
      to 12 healthy males at escalating doses of 50, 100 and 200 mg, and the
      concentrations of [2-(13)C]uracil, [2-(13)C]5,6-dihydrouracil and beta
      ureidopropionic acid (ureido-(13)C) in plasma and urine and (13)CO2 in breath
      were measured by liquid chromatography-tandem mass spectrometry and gas
      chromatograph-isotope ratio mass spectrometry, respectively. RESULTS: The
      pharmacokinetics of [2-(13)C]uracil were nonlinear. The elimination half-life of
      [2-(13)C]5,6-dihydrouracil was 0.9-1.4 h, whereas that of [2-(13)C]uracil was 0.2
      0.3 h. The AUC of [2-(13)C]5,6-dihydrouracil was 1.9-3.1 times greater than that
      of [2-(13)C]uracil, whereas that of ureido-(13)C was 0.13-0.23 times smaller. The
      pharmacokinetics of (13)CO2 in expired air were linear and the recovery of
      (13)CO2 was approximately 80% of the dose. The renal clearance of [2-(13)C]uracil
      was negligible. CONCLUSION: A PBPK model to describe (13)CO2 exhalation after
      orally administered [2-(13)C]uracil was successfully developed. Using [2
      (13)C]uracil as a probe, this model could be useful in identifying DPD-deficient
      patients at risk of 5-fluorouracil toxicity.

PMID- 16305583
TI  - Semi-mechanistic pharmacokinetic/pharmacodynamic modelling of the antimalarial
      effect of artemisinin.
AB  - PURPOSE: To characterize artemisinin pharmacokinetics (PK) and its antimalarial
      activity in vivo. METHODS: Artemisinin salivary concentration and parasite count
      data were obtained from Vietnamese malaria patients receiving two different
      dosage regimens. PK data were analysed using a previously developed
      semiphysiological model incorporating autoinduction of eliminating enzymes. A
      pharmacodynamic (PD) model reflecting different stages of the parasite life-cycle
      was developed and fitted to the data. The model included visible and invisible
      compartments as well as sensitive, insensitive, and injured parasite stages.
      Salivary artemisinin concentrations functioned as the driving force for the
      observed decrease in the number of parasites. RESULTS: Large interindividual
      variability was observed in both PK and PD data. The PK model described
      reasonably well the observed decrease in salivary concentrations after repeated
      drug administration. The preinduction hepatic extraction ratio of artemisinin was
      estimated to be 0.87 with a volume of distribution of 27 L. Artemisinin half-life
      averaged 0.7 h. Incorporation of a saturable hepatic elimination affecting the
      first-pass extraction as well as a higher intrinsic clearance in female patients
      resulted in the best fit of the model to the data. The PD model described the
      decrease in the number of parasites during the course of treatment well. The
      longest mean transit time of parasites from sensitive, visible to invisible to
      insensitive visible stages was found to be 34.5 h through one life-cycle. The
      half-life of injured parasites was 2.7 h. CONCLUSIONS: The proposed
      semimechanistic PK/PD model successfully described the time course of both
      salivary artemisinin concentrations after repeated dosing and the number of
      parasites in patients treated with the drug.

PMID- 16305584
TI  - Assessment of different methods of inhalation from salbutamol metered dose
      inhalers by urinary drug excretion and methacholine challenge.
AB  - AIMS: Methods to determine the lung delivery of inhaled bronchodilators from
      metered dose inhalers include urinary drug excretion 30 min post inhalation and
      methacholine challenge (PD20). We have compared these two methods to
      differentiate lung delivery of salbutamol from metered dose inhalers using
      different inhalation methods. METHODS: In phase 1 of the study, on randomized
      study days, 12 mild asthmatics inhaled placebo, one and two 100 microg salbutamol
      doses from a breath actuated metered dose inhaler, in randomized fashion on
      different days. In phase 2, they inhaled one 100 microg salbutamol dose from a
      metered dose inhaler using a SLOW (20 l min(-1)) and a FAST (60 l min(-1))
      inhalation technique and a slow inhalation delayed until after they had inhaled
      for 5 s (LATE). Urinary excretion of salbutamol (0-30 min) and PD20 were measured
      after each dose. RESULTS: Following placebo, one and two 100 microg salbutamol
      doses, the geometric mean for PD20 was 0.10, 0.41 and 0.86 mg respectively and
      the mean (SD) urinary drug excretion after one and two doses was 2.25 (0.65) and
      5.37 (1.36) microg, respectively. After SLOW, FAST and LATE inhalations the
      geometric mean for PD20 was 0.50, 0.40 and 0.42 mg, respectively, and mean (SD)
      salbutamol excretion was 2.67 (0.84), 1.90 (0.70) and 2.72 (0.67) microg,
      respectively. Only the amount of drug excreted during the FAST compared with the
      SLOW and LATE inhalations showed a statistical difference (95% confidence
      interval on the difference 0.12, 1.54 and 0.06, 1.59 microg, respectively).
      CONCLUSIONS: Urinary salbutamol excretion but not PD20 showed differences between
      the inhalation methods used. When using a metered dose inhaler slow inhalation is
      better and co-ordination is not essential if the patient is inhaling when they
      actuate a dose of the drug.

PMID- 16305585
TI  - Vasodilator effects of the endothelin ET receptor selective antagonist BMS-193884
      in healthy men.
AB  - AIMS: A number of endothelin receptor antagonists (ERAs) are currently in
      clinical development as potential therapies in states characterized by
      vasoconstriction, such as systemic hypertension. We investigated the haemodynamic
      effects of locally and systemically active doses of BMS-193884, an endothelin A
      (ET(A)) receptor selective ERA, and its influence on vasoconstriction to
      endothelin-1 (ET-1) in healthy men. METHODS: In three separate randomized,
      placebo-controlled studies, the forearm blood flow (FBF) response to intra
      arterial (i.a.) infusion of ET-1 (5 pmol min(-1)) was assessed during i.a. co
      infusion of BMS-193884 (5 and 50 nmol min(-1)), and at 12 and at 24 h after oral
      administration of BMS-193884 (50, 100 and 200 mg at 12 h; and 200 mg at 24 h).
      Data were examined by repeated-measures analysis of variance (anova) with
      treatment and subject as factors. RESULTS: ET-1 caused significant forearm
      vasoconstriction, attenuated after oral dosing with BMS-193884 (200 mg) at 12 (P
      < 0.01) and 24 h (P < 0.0001). BMS-193884 (50 nmol min(-1), i.a.) caused local
      vasodilatation (25 +/- 11%) when infused alone (P = 0.02) and abolished forearm
      vasoconstriction to ET-1 (P < 0.0001 vs. ET-1 alone). Orally, BMS-193884 (200 mg)
      caused a reduction in total systemic vascular resistance at 12 (-14 +/- 9%, P =
      0.03) and 24 h (-12 +/- 7%, P < 0.0001). There was no rise in plasma ET-1 levels.
      CONCLUSION: BMS-193884 causes local and systemic vasodilatation and attenuation
      of local vasoconstriction to ET-1. The absence of a rise in plasma endothelin
      levels suggests BMS-193884 is selective for the ET(A) receptor. This form of
      pharmacodynamic modelling may be useful in the development of ERAs in
      cardiovascular disease.

PMID- 16305586
TI  - Polymorphisms in genes encoding acetylsalicylic acid metabolizing enzymes are
      unrelated to upper gastrointestinal health in cardiovascular patients on
      acetylsalicylic acid.
AB  - BACKGROUND: As acetylsalicylic acid is metabolized by UDP-glucuronosyltransferase
      1A6 (UGT1A6) and cytochrome P450 2C9 (CYP2C9), interindividual differences in
      activity of these enzymes may modulate the effects and side-effects of
      acetylsalicylic acid. The objective of this study was to assess whether
      polymorphisms in UGT1A6 and CYP2C9 genes are related to the prevalence of upper
      gastrointestinal symptoms in cardiovascular patients using acetylsalicylic acid
      for secondary prevention of ischaemic heart disease. METHODS: Blood samples were
      taken from acetylsalicylic acid using patients admitted to the Coronary Care
      Unit. Dyspepsia-related health was evaluated at week 2, using a validated upper
      gastrointestinal complaint questionnaire. A subset of 160 patients responded to a
      survey and were eligible to participate in this study. DNA was isolated and
      UGT1A6 and CYP2C9 genotypes were determined using polymerase chain reaction
      restricted fragment length polymorphism techniques. RESULTS: Seventy per cent of
      the patients returned the questionnaire. UGT1A6 and CYP2C9 variant polymorphisms
      were found in 103 (63%) and 56 (35%) patients, respectively. There was no
      association between gastrointestinal symptoms and UGT1A6 (OR = 0.80, 95% CI =
      0.41-1.56) or CYP2C9 polymorphisms (OR = 0.85, 95% CI = 0.44-1.67). CONCLUSIONS:
      There was no association between polymorphisms in genes encoding for
      acetylsalicylic acid metabolizing enzymes on the prevalence of gastric complaints
      in cardiovascular patients on acetylsalicylic acid.

PMID- 16305587
TI  - Gender specific association of CYP2C9*3 with hyperlipidaemia in Chinese.
AB  - AIMS: To investigate the association of CYP2C9*3 and *6 with hyperlipidaemia in
      Chinese. METHODS: Four hundred and seventy-six Chinese participated in the study,
      including 211 uncomplicated hyperlipidaemic patients and 265 healthy controls.
      PCR-RFLP was used to identify CYP2C9*3 and *6. RESULTS: CYP2C9*6 was not detected
      in this study. The allelic frequency of CYP2C9*3 was 0.039 (95% CI 0.022, 0.056).
      A nonsignificant difference existed in CYP2C9*3 frequencies between males and
      females (P = 0.605, OR = 1.194, 95% CI 0.610, 2.336), patients and controls (P =
      0.063, OR = 0.506, 95% CI 0.244, 1.049) in the total population. However, in the
      female group, CYP2C9*3 frequency in patients with hyperlipidaemia was
      significantly lower than that in controls (P < 0.0001, OR = 0.062, 95% CI 0.008,
      0.476). CONCLUSIONS: The association of CYP2C9*3 with hyperlipidaemia was
      specific for females in this Chinese population.

PMID- 16305588
TI  - Sulphation of o-desmethylnaproxen and related compounds by human cytosolic
      sulfotransferases.
AB  - Naproxen is a nonsteroidal anti-inflammatory drug widely used as an analgesic and
      anti-inflammatory agent. The conjugated forms of naproxen and O-DMN, its
      demethylated metabolite, account for 66-92% of naproxen found in human urine. In
      this study, O-DMN and structurally related compounds were tested as substrates
      for seven isoforms of human cytosolic sulfotransferase (SULT). The SULT2 or
      hydroxysteroid SULT isoforms, SULT2A1 and SULT2B1b, did not show reactivity with
      any of the compounds. All five SULT1 isoforms were active although there was
      variability between SULT isoforms and compounds assayed. O-DMN was sulphated by
      SULT1A1, SULT1B1 and SULT1E1. All five SULT1 isoforms were capable of conjugating
      both alpha-naphthol and beta-naphthol. Apparent Km values for O-DMN sulphation
      were significantly higher than the values for either alpha-naphthol or beta
      naphthol. SULTs 1A1, 1B1 and 1E1 had Kms for O-DMN sulphation of 84 microM, 690
      microM and 341 microM, respectively. These Km values were 40-1150-fold higher
      than the Km values for alpha- and beta-naphthol. The role of the side-chain in O
      DMN sulphation was studied using a series of structurally related beta-naphthol
      compounds as substrates for SULT1A1 and SULT1E1. The presence of lipophilic
      groups increased affinity for both SULT isoforms whereas inclusion of a carboxyl
      group inhibited activity. These studies indicate that O-DMN is sulphated by
      SULT1A1, B1 and 1E1. Because of the high concentrations of SULT1A1 expression in
      human liver and intestines and its higher affinity for O-DMN sulphation, SULT1A1
      may have a role in the first pass metabolism of O-DMN.

PMID- 16305589
TI  - Dramatic change in prescribing of hormone replacement therapy in The Netherlands
      after publication of the Million Women Study: a follow-up study.
AB  - AIMS: To estimate the diffusion of new safety information concerning
      postmenopausal hormonal replacement therapy (HRT) into prescribing practice in
      The Netherlands and to assess the impact of revised guidelines on the long-term
      treatment of HRT. DESIGN: Cross-sectional study. SETTING: Community pharmacy
      dispensing data from a population of approximately 450,000 patients in the
      northern and eastern part of The Netherlands. POPULATION: Women aged 45-69 years
      to whom at least one HRT prescription was dispensed between 1 January 2000 and 1
      January 2004. MAIN OUTCOME MEASURES: Annual and quarter prevalences of HRT and
      the proportion of new HRT users, switchers and continuous HRT users per quarter.
      RESULTS: The prevalence of HRT prescribing decreased significantly from 107/1000
      [95% confidence interval (CI) 104, 110] in 2000 to 87/1000 (95% CI 84, 89) in
      2003. The decreasing prevalence was especially evident among the younger age
      groups and was most pronounced among users of oestrogen/progestagen combinations.
      The publication of the Women Health Initiative Study (WHI) was followed by a
      modest decrease in prescribing of HRT, whereas prescribing of HRT declined
      dramatically after publication of the Million Women Study (MWS) in August 2003.
      Among the continuous HRT users in the 4th quarter of 2002, 55% used HRT longer
      than 3 years. This percentage was 53 in the 4th quarter of 2003. CONCLUSIONS: In
      contrast to the release of the WHI study results, publication of the MWS was
      followed by a dramatic fall in prescribing of HRT in The Netherlands. Despite the
      new recommendation that long-term HRT use should be discouraged, the proportion
      of long-term users did not change after the publication of the MWS.

PMID- 16305590
TI  - Usage of paracetamol-containing combination analgesics remains high in primary
      care.
AB  - AIMS: Paracetamol-containing combination analgesics are widely prescribed but the
      use of paracetamol/dextropropoxyphene (co-proxamol) is particularly
      controversial. We aim to examine the prescribing patterns of the paracetamol
      containing analgesics in Ireland. METHODS: A national primary care prescribing
      database was used to investigate patterns of usage. Twenty-six thousand three
      hundred and eighteen patients who were new to therapy with paracetamol and
      paracetamol-containing analgesics between January and June 2002 were identified
      as follows: no previous analgesic medication in the 6 months prior to enrolment
      into the study, and followed up for at least 12 months from the time of
      enrolment. Duration of therapy and the number of prescriptions received post
      enrolment were analyzed according to age. Odds ratios for receiving long-term (>1
      month) compared with short-term (1 month) prescriptions for co-proxamol,
      paracetamol only or a paracetamol combination-type analgesic were calculated for
      women vs. men, and in those aged over 65 vs. those aged under 65 years. RESULTS:
      Co-proxamol was the most commonly prescribed analgesic, accounting for 42% of all
      prescriptions dispensed during 2003. Long-term use of paracetamol-containing
      analgesic preparations was uncommon, with 56.7% receiving only 1 month's
      prescription during the study period. However, women (OR = 1.18, 95% CI 1.07,
      1.28, P < 0.0001) and those over 65 years (OR = 1.71, 95% CI 1.57, 1.86, P <
      0.0001) were more likely to receive a follow-up prescription for co-proxamol, but
      also for paracetamol (women, OR = 1.28, 95% CI 1.16, 1.39; over 65 year olds, OR
      = 2.67, 95% CI 2.44, 2.93) and the paracetamol combinations (women, OR = 1.33,
      95% CI 1.20, 1.47; over 65 year olds, OR = 1.69, 95% CI 1.53, 1.87). CONCLUSIONS:
      Co-proxamol was the most commonly prescribed paracetamol-containing analgesic
      preparation in Ireland. The results may indicate inappropriate use in primary
      care.

PMID- 16305591
TI  - Obstacles and solutions for spontaneous reporting of adverse drug reactions in
      the hospital.
AB  - AIM: To describe the opinions of hospital physicians concerning problems
      regarding the spontaneous reporting of adverse drug reactions (ADRs) and ways to
      solve them. METHODS: A qualitative study was carried out. Fifteen focus groups
      were conducted among physicians working in a tertiary teaching hospital. A total
      of 208 physicians from different medical specialities participated. The focus
      group discussions were recorded by three different observers and the transcripts
      of each session were analysed for issues and themes emerging from the text.
      RESULTS: Four types of obstacles to spontaneous reporting were considered
      particularly important: (i) problems with the ADR(S) diagnosis; (ii) problems
      with the usual workload and lack of time; (iii) problems related to the
      organization and activities of the pharmacovigilance system; (iv) and problems
      related to potential conflicts. The potential solutions suggested for improving
      spontaneous reporting were to define the kind of ADR(S) which should be reported,
      to facilitate an easy contact and quick access to the hospital pharmacovigilance
      system, to facilitate information and support for reporting and feedback of
      pharmacovigilance activities. CONCLUSIONS: The perception of the different
      obstacles by the hospital physicians is an important factor in determining the
      causes of the underreporting of ADRs and addressing these obstacles could lead to
      an improvement in spontaneous reporting. A closer relationship between the
      doctors and the pharmacovigilance centre is suggested as a means of solving these
      problems. More information is needed to improve the spontaneous reporting of
      ADR(S) in specialized healthcare.

PMID- 16305592
TI  - Effects of grapefruit juice on the pharmacokinetics of acebutolol.
AB  - AIMS: We aimed to investigate effects of grapefruit juice on acebutolol
      pharmacokinetics. METHODS: In a randomized cross-over study, 10 healthy subjects
      ingested 200 mL grapefruit juice or water three times daily for 3 days and twice
      on day 4. On day 3, each subject ingested 400 mg acebutolol with grapefruit juice
      or water. The concentrations of acebutolol and its metabolite diacetolol were
      measured in plasma and urine up to 33 h. RESULTS: Grapefruit juice decreased the
      peak plasma concentration (Cmax) of acebutolol by 19% from 872 +/- 207 ng mL(-1)
      to 706 +/- 140 ng mL(-1) (95% CI on the difference -306, -26.4; P < 0.05), and
      the area under the concentration time curve (AUC(0-33 h)) by 7%, from 4498 +/-
      939 ng mL(-1) h to 4182 +/- 915 ng mL(-1) h (95% CI -609, -23.0; P < 0.05). The
      half-life (t1/2) of acebutolol prolonged from 4.0 to 5.1 h (P < 0.05). The time
      to peak concentration and the amount of acebutolol excreted into urine (Ae) were
      unchanged. The Cmax, AUC(0-33 h), and Ae of diacetolol were decreased by 24% (P <
      0.05), 18% (P < 0.05), and 20% (P < 0.01), respectively, by grapefruit juice.
      CONCLUSION: Grapefruit juice caused a small decrease in the plasma concentrations
      of acebutolol and diacetolol by interfering with gastrointestinal absorption. The
      interaction between the grapefruit juice and acebutolol is unlikely to be of
      clinical significance in most of the patients.

PMID- 16305593
TI  - Nasal septal perforation enlargement related to topical ocular steroids.

PMID- 16305594
TI  - Interstitial pneumonitis during lamotrigine therapy.

PMID- 16305595
TI  - Ocular side-effects of tolterodine and oxybutynin, a single-blind prospective
      randomized trial.

PMID- 16305597
TI  - Abstracts of the Dutch Society of Clinical Pharmacology and Biopharmacy meeting
      of April 13th 2005.

PMID- 16305598
TI  - Distribution of intranasal C-zolmitriptan assessed by positron emission
      tomography.
AB  - Nine healthy volunteers aged 18-28 years were recruited into this open, single
      centre, two-phase trial. In phase 1, two volunteers received a single dose of 11C
      zolmitriptan 2.5 mg administered as a nasal spray and then underwent positron
      emission tomography (PET) scanning to determine the most appropriate times for
      scanning in phase 2. In phase 2, six volunteers received two doses and an
      additional volunteer one dose of 11C-zolmitriptan 2.5 mg intranasally. Volunteers
      underwent PET scanning over sectors covering one of the nasopharynx, lungs or
      abdomen, for up to 1.5 h postdose. The brain was also scanned and plasma
      zolmitriptan levels were measured. Almost 100% of the administered dose was
      detected in the nasopharynx immediately after dosing. This declined thereafter to
      about 50% at 20 min and to 35% at 80 min after dosing. Radioactivity appeared
      slowly in the upper abdomen, with 25% of given radioactivity detected at 20 min
      and persisting until 80 min after dosing. Minimal radioactivity was detected in
      the lungs. Radioactivity was detectable within brain tissue suggesting central
      penetration of zolmitriptan. Zolmitriptan in plasma had approached its maximum
      concentration by 15 min postdose. The data indicate initial absorption across the
      nasal mucosa contributing to an early systemic availability. 11C-Zolmitriptan
      administered intranasally was well tolerated.

PMID- 16305599
TI  - High altitude headache. A prospective study of its clinical characteristics.
AB  - Altitude headache (AH) is the most common symptom of high altitude exposure. This
      prospective cross-sectional and analytical study, conducted in the Ecuadorian
      Andes, aimed to explore AH symptomatology, taking into account subjects' views.
      Thirty mountain climbers took part in the Questionnaire Elaboration. The symptoms
      were grouped into three categories: (A) pain dimension (PD)--intensity, location,
      quality, outset form, evolution, exacerbating and relieving elements; (B)
      concurrent symptom dimension (CSD); and (C) feeling/mood dimension (FMD). Ninety
      eight mountain climbers comprised the sample for Field Research. Three
      evaluations were carried out: 4700-5000 m, n=1, and 5700-5800 m, n=2. Pearson's
      correlation coefficient was used to assess internal consistency. Scores between
      0.7 and 1 were considered as significant to assess the strength of association
      between the PD and its different items and CSD and FMD. The following clinical
      features were found: holocranial 65.6%; pulsatile-burst type quality 75.3%;
      oscillating evolution 36.7%; increasing with exercise 49.5%; relieved by rest
      41.8%; concurrent symptoms referred to, anorexia 26.8%, irritability 26.5%, and
      finally pessimism and anxiety feelings 33.2 and 29.5%, respectively. We believe
      that elements provided by us must lead to a new official AH diagnosis criterion.

PMID- 16305600
TI  - Migraine in the Andes and headache at sea level.
AB  - In Cerro de Pasco (CP), Peru (altitude 4338 m) 24% of men have migraine with
      aura. We studied 30 men. Twenty CP natives, examined in CP, were rated using a
      chronic mountain sickness (CMS) score to separate controls (10) from those with
      CMS (10), a maladaptation syndrome in natives to altitude which includes severe,
      recurring headache. We collected white cells in CP and, from the same men, within
      1 h of arrival in Lima (150 m above sea level). Ten normal US men volunteered
      white cells for comparison. After RNA extraction we assessed gene expression by
      reverse transcription-polymerase chain reaction. Low ATP1A1 subunit of the ATPase
      gene mRNA expression in CP was correlated with headache (P=0.002), acral
      paraesthesias (P=0.004) and CMS score (P<0.001). ATP1A1 subunit expression was
      increased in all Andeans in Lima (P<0.001). There were no differences between
      Andean controls in Lima and US controls. Manipulation of Na+/K+ATPase could offer
      relief for migraineurs at sea level.

PMID- 16305601
TI  - Assessment of migraineurs referred to a specialist headache clinic in Singapore:
      diagnosis, treatment strategies, outcomes, knowledge of migraine treatments and
      satisfaction.
AB  - This study aimed to compare (i) migraineurs' diagnosis, treatment strategies and
      satisfaction when treated by community care physicians (CCPs) and at the
      specialist headache clinic; (ii) migraineurs' knowledge of migraine treatments
      and outcomes at baseline and at 3 months' interval. Thirty-eight patients were
      interviewed at baseline visit and 3 months after neurologist consultation, using
      a survey form which consisted of a series of self-designed questions, the MIDAS
      questionnaire and the SF-36 Health Survey. More patients were informed of the
      diagnosis of migraine by the neurologist than by CCPs. Compared with CCPs, the
      neurologist was more likely to employ preventive therapies, prescribe triptans
      and ask patients to keep a headache diary. Patients' number of days with
      headaches in the last 3 months, pain intensity, MIDAS score and five out of the
      eight SF-36 domain scores were significantly improved at the 3 months' interval
      (P<0.05) compared with baseline at the specialist headache clinic. More patients
      recognized migraine-specific therapies and reported satisfaction with treatment
      after the neurologist consultation. This is the first study detailing significant
      improvements in patients' clinical outcomes, knowledge of migraine treatments and
      satisfaction after consultation at a specialist headache clinic in Singapore.

PMID- 16305602
TI  - Cervical spine ROM measurements: optimizing the testing protocol by using a 3D
      ultrasound-based motion analysis system.
AB  - The aim of this study was to evaluate the intra- and inter-examiner reliability
      and validity of neck range of motion (ROM) measurements. Thirty-five healthy
      subjects were assessed in all neck movements from two initial positions, sitting
      and standing, actively (open and closed eyes) and passively by using a 3D
      ultrasound-based motion analysis device (Zebris). Three tests were employed to
      assess intra-examiner reliability and two examiners used for the inter-examiner
      reliability. X-rays in neck flexion and extension were used to validate the
      Zebris system. The standing position yielded higher intraclass correlation
      coefficient (ICC) values (>0.86) with less error [smallest detectable difference
      (SDD)<13.8%] than sitting (ICC>0.79, SDD<14%). Passive assessment of neck ROM
      presented better reproducibility than active assessment with open or closed eyes
      in both positions. The inter-examiner reliability was moderate (ICC=0.43-0.68).
      The correlation between the Zebris system and X-rays was high in both flexion and
      extension movements. The results showed that the most reliable protocol for
      assessment of neck ROM is a passive measurement in the standing position. The
      measurements were well validiated against X-rays and the experience of the
      investigators must be considered before any comparison among studies is employed.

PMID- 16305603
TI  - Migraine and probable migraine--results of FRAMIG 3, a French nationwide survey
      carried out according to the 2004 IHS classification.
AB  - The 2004 International Headache Society (IHS) classification of headache
      disorders introduced the new category of probable migraine defined by the
      existence of all but one of typical migraine criteria. FRAMIG 3, the first
      nationwide population-based survey performed in France using the 2004 IHS
      classification, assessed the prevalence of probable migraine and compared its
      features and management with those of strict migraine. Of a representative sample
      of 10,532 adult subjects interviewed, 1179 subjects (11.2%) were diagnosed as
      having strict migraine and 1066 (10.1%) as having probable migraine. The
      criterion most frequently missing was typical headache duration (4-72 h) and most
      subjects with probable headache had shorter average headache duration. Migraine
      severity and disability, although lower than those noted in subjects with strict
      migraine, were significant in subjects with probable migraine and quality of life
      impairment was identical among the two groups of migraine sufferers. Strict and
      probable migraine, which have similar prevalence and impact on migraine subjects,
      deserve similar medical and therapeutic management.

PMID- 16305604
TI  - Efficacy of multidisciplinary treatment in a tertiary referral headache centre.
AB  - Despite the high prevalence of headaches, multidisciplinary headache clinics are
      few and their efficacy still needs validation. We set out to describe the
      procedures, characterize the patients and evaluate the treatment results in
      Danish Headache Centre. All clinical records for patients discharged in 2002 were
      systematically reviewed. Diagnoses were classified in accordance with ICHD-II.
      Outcome results were analysed with respect to headache diagnoses, frequency,
      intensity, absence from work and medication use. Five hundred and five patients
      were included and 336 were eligible for the study. Mean age was 46 years and
      male/female ratio 1:2.4. For patients without medication overuse headache (MOH) a
      reduction in headache frequency (P<0.01) and intensity (P<0.05) was seen for
      frequent episodic and chronic tension-type headache (TTH), migraine, cluster and
      other headaches. No reduction was seen in post-traumatic headache. Absence from
      work decreased significantly for migraine (P<0.001) and frequent episodic TTH
      (P<0.05). For patients with MOH a reduction in headache frequency was seen for
      TTH and migraine (P<0.001). A specialized headache centre is valuable in
      treatment of patients with complex headache disorders.

PMID- 16305605
TI  - The 3p21.1-p21.3 hereditary vascular retinopathy locus increases the risk for
      Raynaud's phenomenon and migraine.
AB  - Previously, we described a large Dutch family with hereditary vascular
      retinopathy (HVR), Raynaud's phenomenon and migraine. A locus for HVR was mapped
      on chromosome 3p21.1-p21.3, but the gene has not yet been identified. The fact
      that all three disorders share a vascular aetiology prompted us to study whether
      the HVR haplotype also contributed to Raynaud's phenomenon and migraine in this
      family. Whereas the parent-child transmission disequilibrium test (TDT) did not
      reach significance, the sibling TDT revealed that the HVR haplotype harbours a
      susceptibility factor for Raynaud's phenomenon and migraine. Identification of
      the HVR gene will improve the understanding of the pathophysiology of HVR,
      Raynaud's phenomenon and migraine.

PMID- 16305606
TI  - Migraine in Diderot's Encyclopedia: an historical mainstream text.

PMID- 16305607
TI  - Intracranial hypotension following repeated epidural injections of steroids.

PMID- 16305608
TI  - A patient with orgasmic headaches converting to concurrent orgasmic and benign
      exertional headaches.

PMID- 16305609
TI  - 'Hair-wash headache'--an unusual trigger for migraine in Indian patients.

PMID- 16305612
TI  - Stem Cell Transplantation in Children: Current Results and Controversies.
      Proceedings of a meeting. Scottsdale, Arizona, USA, 20-22 January 2005.

PMID- 16305613
TI  - Factors predicting success or failure associated with common types of
      transplants.
AB  - The ability to predict clinical outcomes is essential to accurate medical
      decision analysis. Many accepted bone marrow transplant related prognostic
      variables are derived from data that is over 20-years old and may or may not be
      applicable to current medical practice. This report reviews both older data
      concerning bone marrow transplantation prognostic factors as well as more current
      reports. In addition to pretransplant variables, this review examines easily
      measured post-transplant variables that may affect prognosis, as well as data
      concerning the cellular component of the infused graft in both allogeneic and
      autologous transplantation.

PMID- 16305614
TI  - Critical care of the pediatric hematopoietic stem cell recipient in 2005.
AB  - Among the most challenging patients cared for in critical care medicine are the
      recipients of hematopoietic stem cell transplantation (HSCT). HSCT is now widely
      used as a definitive therapy for the treatment of pediatric malignancies and
      inborn errors of metabolism. Critical care services are required for treatment of
      complications of HSCT. Formerly thought to have an essentially futile prognosis,
      outcomes from critical care of HSCT patients have demonstrated steady improvement
      in many areas during the past two decades. Improvements in the management of
      respiratory failure, sepsis, and multiple organ system failure have resulted from
      improvement in oncology and critical care practices. Herein, we review the
      methods available for outcomes prediction, recent advances in critical care of
      HSCT patients, and possible directions for future investigation.

PMID- 16305615
TI  - Acute lung injury after allogeneic stem cell transplantation: from the clinic, to
      the bench and back again.
AB  - Allogeneic hematopoietic stem cell transplantation (SCT) is the only curative
      therapeutic option for a number of malignant and non-malignant conditions, but
      the success of this treatment strategy is limited by several side effects.
      Diffuse lung injury is a major complication of SCT that responds poorly to
      standard treatment and significantly contributes to transplant related morbidity
      and mortality. Lung injury occurs in both acute and chronic forms and can be
      either infectious or non-infectious in nature. Acute, non-infectious lung injury
      following SCT has been defined as idiopathic pneumonia syndrome (IPS). This
      review will outline the clinical spectrum, risk factors, and pathogeneses of IPS
      and discuss how current approaches to therapy are being influenced by insights
      generated using animal models of disease.

PMID- 16305616
TI  - Granulocyte-colony stimulating factor primed bone marrow and granulocyte-colony
      stimulating factor mobilized peripheral blood stem cells are equivalent for
      engraftment: which to choose?
AB  - The first reported bone marrow transplant was published in 1939, although it was
      deemed unsuccessful. Between 1957 and 1965, numerous reports of bone marrow
      transplants, many of which were successful, were published for patients with
      irradiation injury, aplastic anemia, leukemia, lymphoma, and myeloma. Sources of
      marrow were autologous, isologous, and homologous (often unrelated, including
      cadaveric) donors. Bone marrow infusion was shown to be safe. It was also
      demonstrated that an aliquot of marrow, removed (harvested) from the ileum, had
      sufficient hematopoietic stem cells (SC) to repopulate the marrow and restore
      blood counts after myeloablation. For about 20 yr, bone marrow was the only
      source of hematopoietic stem cells (HSC) for transplantation. The first reported
      autologous peripheral blood HSC transplant was recorded in 1981 using
      chemotherapy 'mobilized' SC collected by leukapheresis. Mobilization is defined
      for these purposes to be any treatment that enhances the number of HSC in the
      blood such that the collection contains sufficient HSC to repopulate the marrow
      and restore blood counts after myeloablation. Since the early 1990s, SCT using
      blood-derived stem cells has become very popular and very common. The principal
      reason is that mobilized (whether by H growth factor or during recovery after
      chemotherapy) blood-derived stem cells engraft more rapidly than do marrow
      derived stem cells. On the one hand, bone marrow was always harvested in the
      resting, unperturbed state (steady state). On the other hand, blood stem cells
      (BSC) were virtually always collected after mobilization, usually with
      granulocyte-colony stimulating factor (G-CSF). There is one report of collection
      of steady state BSC used for transplantation, and slow engraftment was
      documented. Bone marrow was never harvested after either chemotherapy or growth
      factor (priming). It is the mobilization (most often with G-CSF alone or after
      chemotherapy) of BSC that produces more rapid engraftment than for steady state
      marrow stem cells (MSC). This contribution shows the data that changes the old
      paradigm to a new paradigm which states bone MSC and BSC engraft identically if
      collected after the same pretreatment of the donor with growth factor.

PMID- 16305617
TI  - Emerging viral infections after hematopoietic cell transplantation.
AB  - This overview summarizes recent data on emerging viruses after hematopoietic cell
      transplantation (HCT), including adenovirus, BK virus, human metapneumovirus
      (hMPV), and human herpesvirus (HHV) 6. The increased recognition of these
      infections is due to improved molecular detection methods, increased surveillance
      and more profound immunosuppression in the host. Adenovirus can cause serious
      disease especially in T-cell depleted transplant recipients. Adenovirus viremia
      is an important risk factor for disease in this setting. BK virus has been
      associated with hemorrhagic cystitis in HCT recipients. BK viremia is
      significantly associated with hemorrhagic cystitis. hMPV shows a seasonal
      distribution and can cause fatal pneumonia in HCT recipients. hMPV may be the
      etiology of some cases previously categorized as idiopathic pneumonia syndrome.
      HHV-6 commonly leads to viremia in HCT recipients. HHV-6 has been strongly
      associated with encephalitis and delayed platelet engraftment. Prospective
      studies are needed to further examine epidemiology, disease associations, and
      management strategies for these viruses.

PMID- 16305618
TI  - X-linked adrenoleukodystrophy: therapeutic approaches to distinct phenotypes.
AB  - X-linked adrenoleukodystrophy (X-ALD) in males can present with eight distinct
      phenotypes, which vary greatly in respect to phenotypic expression, age of onset
      and rate of progression and therapy. The plasma very long chain fatty acid assay
      permits precise diagnosis and is already abnormal at birth. The clinical
      features, molecular biology, pathogenesis, and therapeutic approaches, including
      the indications for Hematopoietic Stem Cell Transplants (HCT) and dietary therapy
      are discussed, with emphasis on the asymptomatic, childhood cerebral, and
      adrenomyeloneuropathy phenotypes. The rationale for neonatal screening and the
      profound effect that such screening would have on the therapy of X-ALD, including
      the role of HCT, are discussed.

PMID- 16305619
TI  - Reduced intensity transplants (RIT) in pediatrics: a review.
AB  - We describe the experience with reduced intensity transplants (RIT) in pediatric
      patients and review the basis for this approach using adult examples and series
      of patients. We report the experience with RIT in two pediatric studies.

PMID- 16305620
TI  - Approaches to graft-vs-host disease.
AB  - Graft-vs-host disease (GVHD) is one of the most difficult problems in stem cell
      transplantation. It is best considered in the context of the normal immune
      response. The role of the immune system is to identify and eliminate foreign
      antigens. In the case of GVHD, the antigens are minor histocompatibility antigens
      (mHA) recognized in an inflammatory milieu. The immune system cannot reasonably
      be expected to selectively recognize microbial antigens and ignore mHA. This
      approach would require the generation of selective tolerance--something that
      clearly occurs but which we have frustratingly little control over. While we can
      often treat and remit even life-threatening GVHD, the consequence has been the
      development of fatal opportunistic infections. The challenge is to change our
      style of thinking about GVHD to allow a transition from a 'nuclear winter'
      approach that controls GVHD at the price of infection, to a more selective
      patient approach that recognizes the limitations of immunosuppressive therapy.

PMID- 16305621
TI  - Tissue typing for hematopoietic cell transplantation: newer techniques and newer
      antigens for which cross-matching is helpful.
AB  - Refinements in human leukocyte antigen (HLA) typing techniques for hematopoietic
      cell transplantation (HCT) have permitted a more precise assessment of donor
      recipient histocompatibility, which has impacted transplantation outcomes. More
      recently, differences in transplant outcomes associated with killer
      immunoglobulin-like receptor compatibility have emphasized the potential
      importance of natural killer (NK) cell typing in HCT. This article reviews the
      current state of the art for HCT donor selection based on both HLA and NK cell
      typing.

PMID- 16305622
TI  - Fanconi's anemia, transplantation, and cancer.
AB  - Patients with Fanconi's Anemia (FA) have high rates of congenital physical
      abnormalities, bone marrow failure, leukemia, and solid tumors. Stem cell
      transplant (SCT) is often effective in curing bone marrow failure, but high-risk
      patients, particularly those whose donor is not a human leukocyte antigen matched
      sibling, are vulnerable to early mortality from transplant-related complications.
      Long-term survivors of SCT have risks of solid tumors (particularly of the oral
      cavity), which are even higher than the already high 'baseline' risk of neoplasia
      in untransplanted FA patients. In this group, the major types of cancer are head
      and neck squamous cell carcinomas, and gynecologic malignancies. Rapid evaluation
      of new SCT preparative regimens would be useful in improving both short-term and
      long-term results.

PMID- 16305623
TI  - Life-threatening hemophagocytic syndromes: current outcomes with hematopoietic
      stem cell transplantation.
AB  - Life-threatening hemophagocytic syndromes represent a subset of genetic disorders
      of inflammation. Many are rapidly lethal and can only be definitively treated at
      the present time with allogeneic hematopoietic stem cell transplantation (HSCT).
      In this report, current results with allogeneic transplantation for
      Hemophagocytic Lymphohistiocytosis (HLH) are described. HLH typically presents
      symptomatically during infancy and early childhood and can be identified by a
      constellation of numerous physical findings and laboratory tests indicative of
      overwhelming inflammation. The majority of patients with familial HLH lack
      natural killer (NK) cell function; in approximately 50% of cases the specific
      underlying genetic cause can now be discerned. Effective treatment consists of
      initial combination therapy with proapoptotic chemotherapy (typically etoposide)
      and anti-inflammatory therapies (principally steroids) in addition to aggressive
      supportive care, followed by allogeneic HSCT from the best available donor. Over
      the past 25 yr, through collaborative worldwide efforts, survival of children
      with HLH and related disorders has improved from 5% at 1 yr after diagnosis to
      greater than 50% 3-5 yr after diagnosis.

PMID- 16305624
TI  - C-terminal PAL motif of presenilin and presenilin homologues required for normal
      active site conformation.
AB  - The Alzheimer's disease-associated beta-amyloid peptide is produced through
      cleavage of amyloid precursor protein by beta-secretase and gamma-secretase.
      gamma-Secretase is a complex containing presenilin (PS) as the catalytic
      component and three essential cofactors: Nicastrin, anterior pharynx defective
      (APH-1) and presenilin enhancer-2 (PEN-2). PS and signal peptide peptidase (SPP)
      define a novel family of aspartyl proteases that cleave substrates within the
      transmembrane domain presumptively using two membrane-embedded aspartic acid
      residues for catalysis. Apart from the two aspartate-containing active site
      motifs, the only other region that is conserved between PS and SPP is a PAL
      sequence at the C-terminus. Although it has been well documented that this motif
      is essential for gamma-secretase activity, the mechanism underlying such a
      critical role is not understood. Here we show that mutations in this motif affect
      the conformation of the active site of gamma-secretase resulting in a complete
      loss of PS binding to a gamma-secretase transition state analog inhibitor, Merck
      C. Analogous mutations in SPP significantly inhibit its enzymatic activity.
      Furthermore, these mutations also abolish SPP binding to Merck C, indicating that
      SPP and gamma-secretase share a similar active site conformation, which is
      dependent on the PAL motif. Exploring the amino acid requirements within this
      motif reveals a very small side chain requirement, which is conserved during
      evolution. Together, these observations strongly support the hypothesis that the
      PAL motif contributes to the active site conformation of gamma-secretase and of
      SPP.

PMID- 16305625
TI  - Amyloid precursor protein-mediated free radicals and oxidative damage:
      implications for the development and progression of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a late-onset dementia that is characterized by the
      loss of memory and an impairment of multiple cognitive functions. Advancements in
      molecular, cellular, and animal model studies have revealed that the formation of
      amyloid beta (Abeta) and other derivatives of the amyloid precursor protein (APP)
      are key factors in cellular changes in the AD brain, including the generation of
      free radicals, oxidative damage, and inflammation. Recent molecular, cellular,
      and gene expression studies have revealed that Abeta enters mitochondria, induces
      the generation of free radicals, and leads to oxidative damage in post-mortem
      brain neurons from AD patients and in brain neurons from cell models and
      transgenic mouse models of AD. In the last three decades, tremendous progress has
      been made in mitochondrial research and has provided significant findings to link
      mitochondrial oxidative damage and neurodegenerative diseases such as AD.
      Researchers in the AD field are beginning to recognize the possible involvement
      of a mutant APP and its derivatives in causing mitochondrial oxidative damage in
      AD. This article summarizes the latest research findings on the generation of
      free radicals in mitochondria and provides a possible model that links Abeta
      proteins, the generation of free radicals, and oxidative damage in AD development
      and progression.

PMID- 16305627
TI  - Combined Reparative Approaches for Dilated Failing Ventricles.
AB  - (J Card Surg 2005;20:S1-S2).

PMID- 16305626
TI  - Overexpression of dopamine receptor genes and their products in the postnatal rat
      brain following maternal n-3 fatty acid dietary deficiency.
AB  - A combination of PCR-Select cDNA subtraction and gene array hybridization was
      used to identify differentially expressed genomic markers in brains of rats fed
      for 3 weeks in utero and 2 weeks after birth on an n-3 polyunsaturated fatty acid
      (PUFA)-deficient diet supplied to dams. Total RNA was isolated, switch mechanism
      at 5'-end of the RNA transcripts (SMART) applied and used for PCR-Select
      subtraction of PUFA-deficient and adequately-fed control preparations. Subtracted
      and amplified ds-cDNA end-products were fragmented, terminally labeled with
      biotin-ddUTP and hybridized with a RN-U34A gene array. A 10-fold increase in
      potential genes with log2(Tester/Driver) = 1.4 was found compared with
      traditional gene array technology when the same chip was tested using non
      subtracted targets. Reverse transcription-real-time relative PCR confirmed 30% of
      the transcripts. Among the validated transcripts, D1 and D2 receptors for
      dopamine (DA), were most prominent among a number of over-expressed
      neurotransmitter receptors and retinoic acid receptor (RXR alpha-2 and alpha-1).
      Immunohistochemical staining of brain sections from 2-week-old pups revealed a
      substantial enrichment of the D2 receptor in discrete regions of the mesolimbic
      and mesocortical pathways as well as in a large number of brain areas from the n
      3 PUFA-deficient pups. Punches of the same areas run on western blots showed
      similar results. The overwhelming expression of D1 and D2 receptors may be
      attributed to a behavioral hypersensitivity caused by the possible impairment of
      DA production during brain development, which may have implications in certain
      disorders of the nervous system.

PMID- 16305628
TI  - Static cardiomyoplasty with synthetic elastic net suppresses ventricular
      dilatation and dysfunction after myocardial infarction in the rat: an acute
      study.
AB  - BACKGROUND: Wrapping around the heart (static cardiomyoplasty) may help prevent a
      failing left ventricle (LV) from dilatation but may also interfere with diastolic
      relaxation, resulting in restrictive hemodynamics and diastolic heart failure. We
      developed a synthetic net with a dual elasticity and tested its effect early
      after induced myocardial infarction (MI) in the rat. METHODS: In rats undergoing
      occlusion of the left anterior descending artery (LAD) with and without cardiac
      wrapping, pressure-volume (PV) relationships were successively analyzed before,
      after intravenous volume load (saline 1% of body weight over 30 sec), and 10 to
      40 minutes after LAD occlusion. In each situation, end-diastolic and end-systolic
      PV relationships were defined and LV size and function compared under
      standardized loading conditions. RESULTS: Ischemic increase in LV end-diastolic
      and end-systolic volumes was suppressed in a similar magnitude in NET with rats,
      resulting in preserved stroke volume and ejection fraction early after MI. While
      the presence of the net yielded a significant hemodynamic difference in response
      to acute volume load before ischemia, the difference was no longer apparent in
      the ischemic heart after LAD ligation. CONCLUSION: Static cardiomyoplasty using a
      synthetic elastic net significantly suppresses ischemic LV dilatation and
      dysfunction without restriction immediately after MI in the rat. The long-term
      result is pending. Net material and elasticity needs to be adjusted for optimal
      girdling effect, or greatest benefits with least functional compromise.

PMID- 16305629
TI  - Gene expression analysis of human tissue from patients with cardiomyopathies: a
      new tool for guiding therapies in the future?
AB  - The complete sequencing of the human genome led to the development of a number of
      new molecular technologies. DNA microarrays represent an exciting new tool for
      gene expression analysis in human tissue. Measurements of the expressions of many
      thousands of genes in parallel is possible now. Microarrays may be used for
      various applications in medicine. They can be used to find novel prognostic and
      predictive markers as well as new disease classifications into clinically
      relevant subgroups. While there has been great progress in cancer research in
      this field, there are significantly less expression data available concerning the
      heart. In order to identify genes and pathways involved in the pathogenesis of
      cardiomyopathies, we have looked recently for alterations at cellular and
      molecular levels in heart tissue from cardiomyopathy patients. We showed that a
      special group of genes is differentially regulated in dilated cardiomyopathy. The
      first results in hypertrophic cardiomyopathy also showed similar findings. The
      surgeon's role in the clinical application of gene expression profiling is
      crucial. He provides a link between the patient and the laboratory scientists
      playing a significant role in focusing research on the clinically relevant
      problems. Gene expression profiles may help to better characterize the course and
      prognosis of the individual patient in the future. The long-term goal is to find
      a tool that will help to guide medical and surgical therapies in cardiomyopathies
      and other heart diseases.

PMID- 16305630
TI  - Positron emission tomography reporter gene imaging in the myocardium: for
      monitoring of angiogenic gene therapy in ischemic heart disease.
AB  - Cardiac angiogenic gene therapy has emerged as a novel treatment approach for
      patients with intractable ischemic heart disease, aiming at facilitating
      neovascularization to augment blood flow in the ischemic myocardium by
      introducing genes encoding for angiogenic factors. While several clinical trials
      for cardiac angiogenic gene therapy are currently in progress, there remains a
      discrepancy between impressive preclinical results and their limited clinical
      findings. On the other hand, positron emission tomography (PET) reporter gene
      imaging has been developed to monitor expression of transgenes in vivo. PET
      reporter genes encode for proteins that retain complementary positron-emitting
      tracers (PET reporter probes), and theoretically any therapeutic gene can be
      linked and coexpressed with an appropriate PET reporter gene. Consequently, PET
      reporter gene imaging with a PET reporter probe affords external determination of
      the location, magnitude, and duration of expression of therapeutic genes
      noninvasively. Since PET imaging can be performed in various species ranging from
      mice to humans, in vivo cardiac PET reporter gene imaging could play a critical
      role in identifying the "missing link" as a powerful translational research tool.
      In this article, we discuss the role of PET reporter gene imaging in basic and
      clinical research on cardiac angiogenic gene therapy.

PMID- 16305631
TI  - Partial left ventriculectomy in elderly patients not suitable for heart
      transplantation.
AB  - BACKGROUND: Although donor scarcity and intolerance to immunosuppression tend to
      exclude elderly patients from transplantation, partial left ventriculectomy (PLV)
      has been performed without bias against advanced age. METHODS: Among 392 patients
      undergoing PLV, 61 elderly patients aged 65 or older (> or =65) were compared
      with the rest of the patients in terms of underlying disease, postoperative
      course, and survival time. RESULTS: The aged patients (> or =65) compared to
      younger patients (<65), had ischemic disease (37.7% vs. 19.3%, p < 0.05) more
      frequently than cardiomyopathy (34.4% vs. 43.2%) or valvular disease (23.9% vs.
      16.4%) and underwent lateral PLV (74% vs. 79%) more frequently than extended PLV
      (26% vs. 21%). Although the elderly patients required coronary bypass grafting
      more frequently (39.3% vs.17.2%, p < 0.05), surgical complexity was similar in
      terms of bypass time (63 minutes vs. 63 minutes) and percentage requiring cardiac
      arrest (31% vs. 44%). Despite advanced age, they required comparable ICU care
      (6.6 days vs. 5.4 days) and postoperative hospital stay (12 days vs. 11 days),
      resulting in a low but similar hospital survival (57% vs. 62%) and functional
      capacity after discharge (NYHA class 1.5 vs. 1.4). CONCLUSION: The results
      suggest that PLV can be performed in elderly patients (> or =65 years) with
      comparable risks and benefits with the younger patients, promoting its
      application in patients disqualified for heart transplantation because of age
      criteria.

PMID- 16305632
TI  - A surgical approach to severe congestive heart failure--overlapping
      ventriculoplasty.
AB  - BACKGROUND: Previously we developed a new procedure of overlapping cardiac volume
      reduction (OLCVR) surgery for patients with dilated cardiomyopathy refractory to
      medical treatment. Papillary muscle plication (PMP) when combined with OLCVR may
      achieve a better clinical outcome. PURPOSE: To investigate the early and
      intermediate results of OLCVR with or without PMP. METHODS: Twenty-five patients
      (21 males, 4 females, aged 60 +/- 13 years) with either ischemic (n = 7) or
      nonischemic (n = 18) dilated cardiomyopathy underwent either isolated OLCVR (n =
      11; Original Group) or PMP combined with OLCVR (n = 14; Integrated Group).
      RESULTS: Early deaths occurred in two (8%) from a noncardiac cause and late
      deaths in six, two from a cardiac and four from a noncardiac cause. Postoperative
      data in survivors were significantly improved in terms of NYHA functional class
      (from 3.6 +/- 1.9 to 1.6 +/- 1.1), ejection fraction (from 18 +/- 6% to 31 +/-
      8%), left ventricular diastolic dimension (from 73 +/- 9 to 65 +/- 6 mm), and
      left ventricular end-diastolic volume index (from 194 +/- 81 to 128 +/- 43 mL/m2)
      (p < 0.05) in selected comparative cases. One-year crude and cause-specific
      survivals were 70.9% and 83.1%, respectively, at a mean follow-up of 12.8 months.
      One-year crude survival of the Integrated and Original Group was 85.7% and 55.6%,
      respectively (p = 0.24). CONCLUSIONS: Although limitations exist in evaluating
      operative results, we consider OLCVR to be a relatively safe and effective
      procedure for selected patients with dilated cardiomyopathy. The addition of PMP
      to OLCVR may enhance the elliptic formation of left ventricle shape and improve
      mitral valve tethering, but further study is mandatory.

PMID- 16305633
TI  - Volume Reduction Surgery for Dilated Left Ventricle-Is It Time for Another
      Progress Report?
AB  - (J Card Surg 2005;20:S3-S4).

PMID- 16305634
TI  - Angiographic and hemodynamic follow-up of patients after partial left
      ventriculectomy.
AB  - Angiographic, Doppler-echocardiographic and hemodynamic studies early (+6 days)
      and late (+180 days) after partial left ventriculectomy (PLV) on 24 patients
      revealed that PLV decreased end-systolic volume (or dimension) more than the end
      diastolic volume (or dimension), improving stroke volumes (or contractile
      excursion), and doubling ejection fraction (or fractional shortening). Results of
      PLV appeared to depend on a balance between improved systolic contractility and
      reduced diastolic performance. All these survivors had improved diastolic
      relaxation, suggesting myocardial viability is a prerequisite for PLV to be
      successful.

PMID- 16305635
TI  - Early and mid-term results of left ventricular volume reduction surgery for
      dilated cardiomyopathy.
AB  - OBJECTIVE: To evaluate structure-oriented left ventricular volume reduction
      surgery (LVVRS). The purpose of this study was to report the early and mid-term
      results of left volume reduction surgery for dilated cardiomyopathy (DCM).
      METHODS: We performed LVVRS on 29 patients with DCM. The age of the patient
      ranged from 8 to 73 years (mean 58 +/- 18 years). There were 19 male patients
      (63%). Twenty-three patients were ischemic, 5 were non-ischemic, and 1 had
      salcoidosis. Twenty-three patients were in New York Heart Association class III
      or IV. Fourteen patients underwent the Dor operation, 11 underwent a septal
      anterior ventricular exclusion operation, and 6 underwent a modified Batista
      operation. Fifteen patients underwent mitral annuloplasty and 2 patients had
      mitral valve replacement. All patients were divided into two groups, a Dor group
      (n = 14) and non-Dor group (n = 15). Postoperative early results and mid-term
      survival rate were compared between the two groups. RESULTS: Hospital mortality
      was 13.8% (4/29). The causes of death were low-output syndrome (n = 3) and septic
      shock (n = 1). Survival rate was 80% at 1 year and 72% at 3 years. Two-year
      survival rate of Dor and non-Dor groups were 69.8% and 93.8%, respectively (p =
      0.099). CONCLUSIONS: Early and mid-term results of LVVRS were satisfied, and the
      non-Dor operation tended to be superior in mid-term survival to the Dor
      operation. Long-term follow-up is warranted.

PMID- 16305636
TI  - Initial safety and feasibility clinical trial of the myosplint device.
AB  - BACKGROUND: The Myocor Myosplint device is a passive implantable device for the
      treatment of heart failure by changing the geometry of the left ventricle (LV).
      AIM: The purpose of this evaluation was to describe the first human experience
      with the Myosplint device to demonstrate safety and feasibility. METHODS: Of the
      first consecutive 21 patients, 9 patients received a Myosplint device alone while
      12 patients underwent a mitral valve repair as well. Safety and efficacy data
      were gathered at enrollment and during follow-up. RESULTS: No serious device
      related adverse events or device failures were observed. Three patients died
      during the follow-up period, and 2 patients underwent heart transplantation.
      There was a significant improvement in the New York Heart Association (NYHA)
      functional class from 3.0 +/- 0.3 at baseline to 2.1 +/- 0.7 at 6 months (p =
      0.001). Both LV end-diastolic and end-systolic volumes had decreased at follow
      up. The LV ejection fraction significantly increased in the Myosplint alone group
      (from 17.1 +/- 4.0% at baseline to 21.8 +/- 4.1% at 3 months and 23.1 +/- 7.2% at
      6 months) but not in the Myosplint and mitral valve repair group. The mitral
      regurgitation (MR) grade had a significant (p = 0.002) linear relationship with
      the NYHA functional class. CONCLUSIONS: The initial clinical experience of the
      Myosplint device demonstrated both safety and feasibility, validating the LV
      shape change concept in humans. A remodeling solution must, however, include MR
      resolution, to illustrate the need for a device that can simultaneously reduce or
      eliminate functional MR off-pump.

PMID- 16305637
TI  - Left ventricular volume reduction surgery: The 4th International Registry Report
      2004.
AB  - BACKGROUND AND METHODS: An international registry of left ventricular volume
      reduction (LVVR) procedures, including partial left ventriculectomy, has been
      expanded, updated, and refined to include 568 cases voluntarily reported from 52
      hospitals in 12 countries. RESULTS: Gender, age, ventricular dimension,
      ethnology, myocardial mass, presence or absence of mitral regurgitation, as well
      as transplant indication, had little effect on event-free survival, which was
      defined as either absence of death or ventricular failure requiring mechanical
      assist or transplantation. Poor preoperative patient condition such as New York
      Heart Association classification IV, depressed contractility and decompensation
      requiring an emergency procedure were associated with reduced event-free
      survival. Other risk factors included an early surgery date, lack of experience,
      dilated cardiomyopathy as the underlying pathology and extended myocardial
      resection. Performance of LVVR reached a peak by 1998, but was largely abandoned
      by 2001, except in Asia, where experienced institutes continue to perform it in
      patients in better condition with preserved myocardial contractility. CONCLUSION:
      Avoidance of risk factors appears to have contributed to the recent survival
      improvement and may help stratify patients for LVVR. While performance has been
      decreasing, the concept has been extended to other LVVR and less invasive
      procedures, which are now under clinical trials.

PMID- 16305638
TI  - The BAFF/APRIL system in systemic autoimmune diseases with a special emphasis on
      Sjogren's syndrome.
AB  - Systemic autoimmune diseases, such as Sjogren's syndrome (SS), are characterized
      by a complex aetiology with multiple pathogenic factors. In SS, disturbed B-cell
      biology and humoral immunity including B-cell-activating factor (BAFF)-mediated
      processes have been described. Dysregulated BAFF expression has been described to
      lead to disease progression and perpetuation of humoral autoimmunity. Moreover,
      BAFF has been proposed to contribute to the development of B-cell malignancies.
      In this review, we summarize the current knowledge on BAFF with regard to SS
      pathology and discuss special features such as germinal centre (GC) formation and
      lymphomagenesis. Locally, in SS salivary glands, the reduced level of apoptosis
      among BAFF-expressing cells might lead to longer-existing BAFF expression and
      thereby maintain signalling for tissue-infiltrating B cells to proliferate and
      supposedly to become autoantibody-producing plasma cells. We assume that
      prolonged BAFF signalization may contribute to GC formation and/or lymphoma
      development in the disease. Finally, we discuss possibilities of novel treatments
      targeting the BAFF-system in SS.

PMID- 16305639
TI  - Genetically modified autoactivated cells expressing intracellular forms of GM-CSF
      as a model for regulated administration of cytokines.
AB  - The application of cytokines for immunotherapy is frequently hampered by
      undesirable side effects. To avoid systemic effects, cytokines can be directly
      expressed in the target cells by using gene transfer. However, the uncontrolled
      cellular secretion of cytokines could still exert some undesirable bystander
      effects. Therefore, it is important to develop additional methods for a more
      restricted administration of cytokines. Recently, using the murine granulocyte
      macrophage colony-stimulating factor (mGM-CSF), we have demonstrated that
      cytokines can be targeted to different subcellular compartments as stable and
      biologically active proteins. This model could be used as a method of highly
      restricted administration of cytokines. Here, as model for the proof of
      principle, we have used a cell line (DA-3) strictly dependent on mGM-CSF for
      growth and demonstrated that these cells acquired autonomous growth after gene
      modification with plasmids encoding either extracellular or intracellular forms
      of mGM-CSF. Cell lines expressing secreted forms of mGM-CSF displayed the highest
      rates of autonomous growth and released substantial amounts of mGM-CSF. However,
      cell lines expressing intracellular forms of mGM-CSF also acquired autonomous
      growth induced by a mechanism of restricted autocrine stimulation and did not
      release detectable mGM-CSF to the extracellular medium. Cocultivation experiments
      of DA-3 cell lines expressing intracellular mGM-CSF with unmodified cells showed
      that there was no activation of the bystander cells. Taken together, these
      results support the concept that genes encoding intracellular cytokines may be
      used to provide the desired effect of cytokines on the target cells while
      avoiding the side effects of their uncontrolled secretion.

PMID- 16305640
TI  - Blockade of CTLA-4 promotes airway inflammation in naive mice exposed to
      aerosolized allergen but fails to prevent inhalation tolerance.
AB  - In subjects not developing allergy, inhalation of nonpathogenic protein antigens
      causes no harm and is associated with tolerance induction. Repeated exposure to
      aerosolized ovalbumin (OVA) likewise does not evoke airway inflammation and
      induces inhalation tolerance in experimental animals. The present study explored
      the role of the inhibitory T-cell receptor CTLA-4, in preventing inflammation and
      in establishing inhalation tolerance in response to a protein antigen. Naive
      BALB/c mice were injected intraperitoneally with anti-CTLA-4 monoclonal antibody
      or control immunoglobulin G (IgG) and exposed daily to aerosolized saline or OVA
      over 10 or 20 consecutive days. OVA-specific IgE levels and the inflammatory
      response in airway tissues were assessed 2 days after last exposure. The OVA
      specific IgE response was also evaluated in mice subjected to a subsequent
      immunogenic OVA challenge 18 days after last aerosol exposure. Additional mice
      were made tolerant by 10 days of OVA aerosol exposure and were then subjected to
      an immunogenic OVA challenge combined with CTLA-4 blockade or control IgG
      treatment. Repeated inhalation of aerosolized OVA alone did not cause a pulmonary
      inflammatory response. In contrast, 10 days of OVA exposure combined with
      blockade of CTLA-4 led to development of eosinophilic lung infiltrates, BAL fluid
      eosinophilia, goblet cell hyperplasia and increased OVA-specific IgE. By 20 days
      of OVA exposure and blockade of CTLA-4, the inflammatory response remained. Mice
      exposed to aerosolized OVA for 10 days exhibited greatly reduced OVA-specific IgE
      responses to subsequent immunogenic OVA challenge. Blockade of CTLA-4 during the
      period of OVA aerosol exposure did not prevent this suppression of the OVA
      specific IgE response. Neither did blockade of CTLA-4 during immunogenic OVA
      challenge alter the allergen-specific IgE response. Our results indicate that in
      vivo blockade of CTLA-4 modulates the initial immune response to a protein
      antigen allowing the development of allergen-induced airway inflammation in naive
      mice. However, this initial exaggerated immune response is followed by the
      induction of inhalation tolerance, demonstrating that CTLA-4 signalling is not
      decisive in this process. Our findings also show that once inhalation tolerance
      is established it may not be disrupted by blockade of CTLA-4.

PMID- 16305641
TI  - No role of alpha-Gal in human monocyte-endothelial cell interactions in vitro.
AB  - Vascularized organ xenografts undergoing acute vascular rejection (AVR) are
      infiltrated by innate immune cells such as monocytes/macrophages. Herein, human
      monocyte static and dynamic adhesion to, and migration across, human and porcine
      aortic endothelial cells (HAEC and PAEC) were investigated. To elucidate the role
      of Gal alpha1,3Gal (alpha-Gal) epitopes in these processes in the absence of anti
      Gal antibodies (Ab), this determinant was aberrantly expressed in HAEC. HAEC were
      transduced with a lentiviral vector encoding the porcine alpha1,3
      galactosyltransferase to express alpha-Gal at high frequencies (75-95%). Alpha
      Gal expression on HAEC did not increase their ability to support monocyte
      transendothelial migration or adhesion under either static or flow conditions.
      Porcine and human endothelium supported static adhesion and migration of
      monocytes equally well. However, human monocytes adhered less to PAEC than to
      HAEC (P = 0.03) under flow following human, but not porcine, tumour necrosis
      factor-alpha stimulation. In the absence of anti-Gal Ab, the alpha-Gal epitope
      does not contribute to increased monocyte adhesion to, or migration across,
      endothelium. Thus, inhibiting adhesion receptor-ligand interactions essential for
      the adhesion of human monocytes to porcine endothelium may be more important than
      carbohydrate remodelling of donor pigs to prevent adhesion/infiltration of
      monocytes into organ xenografts during AVR.

PMID- 16305642
TI  - IgG3-mediated enhancement of the antibody response is normal in Fc gammaRI
      deficient mice.
AB  - Antibodies, administered together with their specific antigen, can feedback
      regulate antibody responses to this antigen. IgG1, IgG2a and IgG2b enhance
      antibody responses to soluble protein antigens. This effect is primarily mediated
      by FcRs as enhancement is impaired in FcR gamma-/- mice, reported to lack Fc
      gammaRI and Fc gammaRIII because of deletion of the common FcR gamma chain. Also
      IgG3 can enhance antibody responses. However, this effect is unperturbed in FcR
      gamma-/- mice but severely impaired in complement-depleted animals and in animals
      lacking complement receptor 1 and 2. Although this argues against involvement of
      Fc gammaRs, FcR gamma-/- mice may express one-fifth of the normal levels of Fc
      gammaRI and, in addition, Fc gammaRI has been suggested to bind IgG3. We re
      investigated the dependence of IgG3-mediated enhancement on Fc gammaRs using a
      mouse strain selectively lacking Fc gammaRI and found that IgG3-mediated
      enhancement is completely normal. Unlike IgE and IgG2a, which are both thought to
      enhance T-cell proliferation via FcR-mediated antigen presentation, IgG3 was a
      poor enhancer of T-cell proliferation both in vivo and in vitro. These findings
      argue against a significant involvement of Fc gammaRs in IgG3-mediated
      enhancement of antibody responses and support our previous conclusion that
      complement plays a major role.

PMID- 16305643
TI  - M-ficolin, an innate immune defence molecule, binds patterns of acetyl groups and
      activates complement.
AB  - Ficolins play a role in the innate immune defence as pathogen-associated
      molecular pattern recognition molecules. Three ficolins are found in humans: H
      ficolin, L-ficolin and M-ficolin. L-ficolin and H-ficolin circulate in blood in
      complexes with mannan-binding lectin-associated serine proteases (MASPs) and are
      capable of activating the complement system. L-ficolin shows affinity for
      acetylated compounds and binds to various capsulated strains of bacteria. H
      ficolin has been shown to bind Aerococcus viridans. Less is known about M
      ficolin, but it is thought to be present only on monocytes. We have synthesized
      recombinant M-ficolin and find that it, in a manner similar to L-ficolin, is able
      to bind to acetylated compounds and to associate with recombinant MASP-2. Upon
      binding to M-ficolin ligands, the associated MASP-2 zymogen is activated and
      cleaves C4, thus triggering the complement system. We developed a monoclonal rat
      anti-human-M/L-ficolin antibody and verified by flow cytometric analysis the
      presence of ficolin on the surface of peripheral blood monocytes.

PMID- 16305644
TI  - IL-10 promoter -1082 polymorphism is associated with elevated IL-10 levels in
      control subjects but does not explain elevated plasma IL-10 observed in Sjogren's
      syndrome in a Hungarian cohort.
AB  - The aim of this study was to investigate the frequency of the -1082 polymorphism
      of the interleukin-10 (IL-10) gene and the soluble IL-10 levels in Hungarian
      primary Sjogren's syndrome (SS) patients. Ninety-nine SS patients and 135 healthy
      volunteers were examined. Samples were analysed by the PCR restriction fragment
      length polymorphism method, and IL-10 plasma levels were assessed by a commercial
      enzyme-linked immunosorbent assay. IL-10 plasma levels were higher in the primary
      SS patients (36.4 +/- 57.5 pg/ml, n = 99) compared with the healthy subjects (9.9
      +/- 20.3 pg/ml, n = 135, P = 10(-6)). The elevated IL-10 phenotype of SS patients
      was not associated with increased G allele frequency as reported earlier, while
      in the control group, we found higher IL-10 levels among the subjects who were
      carriers of the GG genotype (17.7 +/- 23.2 pg/ml) as compared with the other two
      genotype carriers (AA 8.98 +/- 16.5 and GA 8.5 +/- 21.1 pg/ml, P = 0.01). Our
      data do not support previous observations indicating an association between
      deregulated IL-10 secretion in SS and higher G allele frequency. However, the
      results clearly demonstrate that GG homozygosity is associated with elevated IL
      10 levels in apparently healthy subjects, but this cannot account for the IL-10
      related specific disease features observed in SS. Thus, other genetic factors
      contribute to the clinical spectrum of this heterogeneous disease at least in the
      Hungarian population.

PMID- 16305645
TI  - Expression of interleukin-17 in ischemic brain tissue.
AB  - Ischemic brain injury is acute local inflammation, leading to accumulation of pro
      inflammatory cytokines. Cytokines influence the recruitment of leucocytes and
      play a key role in the inflammatory injury processes. Recently, a number of
      studies have demonstrated a close relationship between brain ischemia and
      cytokines. Interleukin-17 (IL-17) is a newly identified T-cell-specific cytokine.
      In this study, we evaluated the source and the action of IL-17 over the course of
      cerebral ischemia in rats (Sprague-Dawley) and humans. The levels of IL-17 in the
      ischemic hemisphere of the human brain, which was removed at necropsy, were
      assayed immunohistochemically. In rats, permanent middle cerebral artery
      occlusion (pMCAO) was obtained by inserting nylon monofilament into the right
      external carotid artery, occluding the right middle cerebral artery. The
      expression of IL-17 mRNA in rat was assayed using oligoprobe in situ
      hybridization. IL-17 production by neuroglial cells was assayed by double
      staining using antibody glial fibrillary acidic protein (GFAP) and antibody IL
      17. Levels of IL-17 were elevated in the ischemic hemispheres of human brain
      compared with the opposite normal hemispheres and peaked at days 3-5 after brain
      ischemia. The IL-17-positive cells were found in the ischemic lesion region. IL
      17 mRNA was also elevated in ischemic hemispheres of pMCAO-operated rats, which
      were slightly elevated after 1 h and peaked at 6 days. IL-17 and GFAP double
      stained were extensive in rat ischemic hemisphere. The ischemia-induced IL-17
      expression in human brain reported here for the first time was very similar to
      that in rat model except that the peak was slightly earlier. We found for the
      first time that IL-17 was involved in an intense inflammatory reaction of brain
      ischemic injury in human. In pMCAO-operated rats, our findings suggest that IL-17
      is produced by the neuroglial cells in the brain region undergoing ischemic
      insult. We suggest that in additional to T cells the neuroglial cell may be
      another cellular origin of IL-17 in later progression of brain ischemia.

PMID- 16305646
TI  - Immune response in human visceral leishmaniasis: analysis of the correlation
      between innate immunity cytokine profile and disease outcome.
AB  - We investigated the cytokine profile of cells of the innate immune response and
      its association with active (ACT), asymptomatic (AS) and cured (CUR) human
      visceral leishmaniasis (VL), as well as noninfected (NI) subjects. The frequency
      of cytokine-producing cells was determined after short-term in vitro incubation
      of whole peripheral blood samples with soluble Leishmania antigen (SLA). Our data
      demonstrated a predominant type 2 cytokine profile in NI and ACT. In NI, we
      observed an increase of IL-4+ neutrophils, IL-10+ eosinophils besides a decrease
      of tumour necrosis factor (TNF)-alpha+ eosinophils/monocytes. Yet in ACT, we
      observed an increase of IL-4+ neutrophils and natural killer (NK) cells and IL
      10+ monocytes, a reduced frequency of IL-12+ and IFN-gamma+ eosinophils and lower
      levels of TNF-alpha+ and IL-12+ monocytes. AS presented a mixed profile,
      characterized by an increase of IFN-gamma+ neutrophils/eosinophils and NK cells,
      of IL-12+ eosinophils/monocytes, as well as increase of IL-4+ neutrophils and NK
      cells and IL-10+ eosinophils/monocytes. In contrast, CUR was characterized by a
      type 1 response with an increase of IFN-gamma+ neutrophils/eosinophils and NK
      cells, associated with an increase in IL-12+ monocytes. In conclusion, we show a
      correlation between innate immune cytokine patterns and clinical status of VL,
      suggesting that these cells, in addition to other factors, may contribute to the
      cytokine microenvironment in which Leishmania-specific T cells are primed and to
      disease outcome.

PMID- 16305647
TI  - Pediatric mechanical circulatory support: a new golden era?

PMID- 16305648
TI  - Activation of neutrophil granulocytes in an in vitro model of a cardiopulmonary
      bypass.
AB  - Activated neutrophils play a central role in the pathogenesis of postoperative
      organ dysfunction after surgery with cardiopulmonary bypass. The researchers used
      an in vitro roller pump model to investigate the relative importance of the
      biomaterial, platelets, plasma proteins including activated complement, and flow
      mode on neutrophil activation as shown by the adhesion, degranulation, and
      increased the surface expression of CD11b. Neutrophil adhesion to the biomaterial
      increased with platelet addition, but not with plasma. Biomaterial contact
      activated neutrophils in a serum-free buffer, but was significantly increased by
      activated complement. Platelets increased neutrophil degranulation in a serum
      free buffer but tended to reduce it in plasma. CD11b expression increased in both
      media. Complement activation was higher with neutrophils alone than with
      neutrophils and platelets combined. The roller pump reduced neutrophil adhesion
      and increased degranulation compared to passive rotation. Neutrophil interaction
      with platelets and complement were more important for activation than biomaterial
      contact and use of the roller pump. Improvement of biocompatibility is dependent
      on modifying complement activation and platelet interaction with neutrophils.

PMID- 16305649
TI  - Design considerations of volute geometry of a centrifugal blood pump.
AB  - This article compares two different design techniques that are conventionally
      used in the design of volutes for centrifugal pumps. The imbalanced forces due to
      the geometry of the volute need to be taken into consideration especially in
      centrifugal blood pumps with magnetically suspended impeller. A reduction of
      these forces can reduce the instability of the impeller motion as well as the
      power needed to counteract its influence. Volutes using the constant angular
      momentum (CAM) and the constant mean velocity (CMV) methods were developed and
      modeled numerically. The computational results on the effect of volute geometry
      on the performance of a centrifugal blood pump impeller for six different volutes
      are presented here. For volutes designed using the CAM method, model B (volute
      expansion angle of 3 degrees ) had the lowest radial force of 0.26 N while the
      pressure head generated was 12,900 Pa. For volutes designed using the CMV method,
      model F (1.6 m/s) had the lowest imbalanced force of 0.45 N. However, the
      pressure developed by this pump was also one of the lowest at 10,652 Pa.
      Furthermore, when the peak scalar stresses and the mean exposure time of
      particles for all designs were determined using Lagrangian particle tracking
      method, it was observed that in general, the peak scalar stresses in CAM designed
      volutes are lower than those designed using CMV method. The mean exposure time of
      particles in the pump ranged from 400 to 500 ms. The simulation results showed
      that the volute designed using CAM method was superior to that of a CMV volute in
      terms of the magnitude of the radial force and the peak scalar stresses for the
      same pressure head generated. Results show that the design of volutes for blood
      pumps should go beyond conventional empirical methods to obtain optimal results.

PMID- 16305650
TI  - Computational simulation of a non-newtonian model of the blood separation
      process.
AB  - The aim of this work is to construct a computational fluid dynamics model capable
      of simulating the transient non-Newtonian process of apheresis. A Lagrangian
      Eulerian model has been developed which tracks the blood particles within a two
      dimensional flow configuration. Within the Eulerian method, the fluid mass and
      momentum conservation equations within the separator are solved using the density
      and the viscosity is calculated from the blood particle concentrations.
      Subsequently, the displacement of the blood particles is calculated with a
      Lagrangian method. Hawksley's model for the density of supensions is used in the
      variable density calculation. The viscosity is calculated with two models based
      on Vand's rigid particle suspension viscosity concepts, followed by the flow
      field calculation in the separator. Simulations were performed for various inlet
      hematocrit values and separator lengths. The simulations are in satisfactory
      agreement with experimental results reported in literature, indicating a complete
      separation of plasma and red blood cells (RBCs), as well as nearly complete
      separation of red blood cells and platelets. No hemolysis was observed in the
      simulations because the shear rate remained under the critical value of 150 N/m2.

PMID- 16305651
TI  - The relation between vascular access flow and different types of vascular access
      with systemic hemodynamics in hemodialysis patients.
AB  - Access flow (Qa) has an important effect on systemic hemodynamics in dialysis
      patients. A Qa : cardiac output (CO) ratio higher than 0.3 is considered a risk
      factor for high-output cardiac failure. However, the effect of different types of
      vascular access in hemodialysis patients has not yet been studied. The aim of the
      present study was to assess the relationship between Qa and systemic hemodynamics
      and to compare systemic hemodynamics between patients with elbow/upperarm access
      with forearm access types. Qa, CO, cardiac index (CI), central blood volume
      (CBV), and peripheral vascular resistance (PVR) were studied by the saline
      dilution technique in 58 hemodialysis patients (18 with elbow/upperarm access; 40
      with forearm access types). This article found that Qa was significantly and
      positively related to CO and CI, and inversely related to PVR. CBV, Qa, and
      presence of cardiac failure were independent determinants of CI. Qa and the Qa :
      CO ratio were significantly higher, and PVR significantly lower, in patients with
      elbow/upperarm access compared to patients with forearm access types. When
      patients with cardiac failure were excluded, CO and CI were also significantly
      higher in patients with elbow/upperarm access types. Eleven percent of patients
      with elbow/upperarm fistula had a Qa : CO ratio above 0.3. In conclusion, Qa is
      strongly related to systemic hemodynamics in dialysis patients. In patients
      without cardiac failure, CO and CI are significantly higher in patients with
      elbow/upperarm access compared to patients with forearm access types. However,
      only a small percentage of patients with elbow/upperarm fistulae appeared to be
      in the risk zone for development of high-output cardiac failure.

PMID- 16305652
TI  - The effects of maintenance recombinant human erythropoietin therapy on ambulatory
      blood pressure recordings: conventional, Doppler, and tissue Doppler
      echocardiographic parameters.
AB  - Cardiovascular disease is the major cause of mortality in maintenance
      hemodialysis patients. Left ventricular dysfunction is present in approximately
      80% of these patients and is highly predictive of future ischemic heart disease,
      cardiac failure, and death. Anemia has been identified as one of several risk
      factors responsible for cardiac complications. The treatment of renal anemia with
      recombinant human erythropoietin (rHuEpo) and consequent improvement of cardiac
      performance may reverse pathological changes in left ventricular geometry. In
      this study, the acute and chronic effects of rHuEpo administration on 24-hour
      ambulatory blood pressure recordings and echocardiographic parameters in 30
      rHuEpo-naive maintenance hemodialysis patients were examined. Twenty-four-hour
      ambulatory blood pressure monitoring was performed prior to and after 1 week and
      6 months of rHuEpo administration. The patients underwent echocardiographic
      examination prior to and after 6 months of rHuEpo administration. One week
      treatment with rHuEpo did not cause any significant change in 24-hour ambulatory
      blood pressure recordings. After 6 months of therapy, serum hemoglobin levels
      increased from 8.8 +/- 0.66 g/dL to 10.8 +/- 0.70 g/dL (P < 0.05).
      Echocardiographic examination revealed elevation in ejection fraction (62.26 +/-
      6.84% vs. 69.90 +/- 8.98%, P < 0.05) with reductions in fractional shortening
      (36.70 +/- 4.96% vs. 35.96 +/- 6.32%, P < 0.05), interventricular septum
      thickness (1.21 +/- 0.16 vs. 1.00 +/- 0.16 cm, P < 0.05), and left ventricular
      mass index (148.2 +/- 46.5 g/m2 vs. 93.6 +/- 17.2 g/m2, P < 0.05). Doppler
      echocardiography and tissue Doppler imaging provided additional information in
      comparison with conventional echocardiography. Before treatment, mitral flow E
      wave (E, 0.64 +/- 0.27 vs. 0.82 +/- 0.17 cm/s), mitral flow A wave (A, 0.80 +/-
      0.21 vs. 0.70 +/- 0.21 cm/s), early diastolic velocity of lateral wall (Lateral
      E', 11.2 +/- 2.8 vs. 12.4 +/- 2.3 cm/s), late diastolic velocity of lateral wall
      (Lateral A', 6.7 +/- 2.5 vs. 7.8 +/- 2.1 cm/s), early diastolic velocity of
      septal wall (Septal E', 9.7 +/- 2.9 vs. 11.3 +/- 1.1 cm/s), and late diastolic
      velocity of septal wall (Septal A', 6.4 +/- 2.1 vs. 7.8 +/- 2.0 cm/s) were
      significantly lower in patients than in the controls. Patients and controls have
      similar deceleration time of mitral flow E wave (E Dec, 186 +/- 57.8 vs. 192 +/-
      62.4 ms), isovolumic left ventricular relaxation time (IVRT, 111.9 +/- 30.7 vs.
      91.1 +/- 32 ms), systolic velocity of lateral wall (Lateral S', 7.8 +/- 2.3 vs.
      8.1 +/- 2.0 cm/s), and systolic velocity of septal wall (Septal S', 7.5 +/- 1.9
      vs. 7.7 +/- 1.4 cm/s) values. Therapy with rHuEpo did not cause significant
      changes in E (0.64 +/- 0.27 vs. 0.76 +/- 0.29 cm/s), A (0.80 +/- 0.21 vs. 0.79 +/
      0.23 cm/s), E Dec (186 +/- 57.8 vs. 165.8 +/- 60.1 ms), IVRT (111.9 +/- 30.7 vs.
      101.6 +/- 36.2 ms), Lateral E' (11.2 +/- 2.8 vs. 11.5 +/- 4.4 cm/s), Lateral A'
      (6.7 +/- 2.5 vs. 7.4 +/- 2.1 cm/s), Lateral S' (7.8 +/- 2.3 vs. 8.1 +/- 2.0
      cm/s), Septal E' (9.7 +/- 2.9 vs. 10.0 +/- 1.1 cm/s), Septal A' (6.4 +/- 2.1 vs.
      6.6 +/- 2.0 cm/s), and Septal S' (7.5 +/- 1.9 vs. 7.9 +/- 1.4 cm/s) indicating
      persistence of diastolic dysfunction. In 6 months time, 24-hour ambulatory blood
      pressure recordings, however, tended to be higher (systolic: 125.16 +/- 21.02 mm
      Hg vs. 134.36 +/- 23.98 mm Hg; diastolic: 77.40 +/- 14.47 mm Hg vs. 83.26 +/-
      14.89 mm Hg, P < 0.05). Correction of anemia with rHuEpo results in the elevation
      of blood pressure and reduction in left ventricular mass index. Myocardial
      contraction and relaxation velocities did not improve following regression of
      left ventricular hypertrophy, suggesting the persistance of diastolic
      dysfunction. Doppler echocardiography with tissue Doppler imaging reflects the
      real situation of diastolic function in patients on maintenance hemodialysis.

PMID- 16305653
TI  - Valve replacement surgery in patients with end-stage renal disease: long-term
      results.
AB  - BACKGROUND: The life expectancy of patients with chronic renal failure who are
      dependent on dialysis is very poor. This study was undertaken to determine time
      related outcomes in dialysis patients requiring cardiac valve replacement.
      METHODS: From 1994 to 2001, 29 end-stage renal disease (ESRD) patients on
      hemodialysis (HD) program underwent 30 valve replacement operations: 29 received
      mechanical valves (97%), and one received bioprosthetic valves. The sites of
      valve replacement were 11 aortic (36.7%), 18 mitral (60%), and one both aortic
      and mitral (3.3%). Mean age was 42.46 +/- 14.26 years (range 17-75 years). Follow
      up was completed in 28 patients (96.5%). RESULTS: Early postoperative mortality
      (in the first 30 days) was 3.4% (n = 1). The overall estimated Kaplan-Meier
      survival was 56.7% at 36 months, 46.7% at 60 months, and 43.3% at 96 months. HD
      program was discontinued for two patients after renal transplantation in the
      follow-up period. All patients, except the one with bioprosthesis, used warfarin
      sodium for anticoagulation and none of them had bleeding. One of the patients had
      a major cerebrovascular accident (CVA) and another one had a minor CVA at the
      follow-up (6.7%). CONCLUSIONS: Life quality is better and life expectancy is
      longer after valve replacement in ESRD patients who have valvular disease. Also,
      longer life expectancy increases the probability for finding donors for kidney
      transplantation.

PMID- 16305654
TI  - Pyruvate improves neutrophilic nitric oxide generation in peritoneal dialysis
      solutions.
AB  - To investigate the effects of pyruvate (Pyr)-based peritoneal dialysis solutions
      (P-PDS) on neutrophilic nitric oxide (NO) generation, we incubated human
      peripheral neutrophils in dL-lactate (Lac, 40 mM)-based PDS and equimolar P-PDS,
      and Hanks' balanced salt solution at various pH and high glucose (HG) levels,
      respectively. The production of NO in various test solutions was determined based
      on the Griess reaction. Acidic pH, high Lac, and HG induced an acute and
      substantial inhibition of neutrophilic NO, whereas Pyr in PDS significantly
      improved the NO generation in both acidic pH and physiological pH, and also in HG
      conditions. The Pyr protection may be associated with the improvement of glucose
      metabolic pathways in addition to its alkalization.

PMID- 16305655
TI  - Inflammatory markers and hepatocyte growth factor in sustained hemodialysis
      hypotension.
AB  - Hypotension is an important complication of hemodialysis. The pathogenesis of
      this complication remains unclear. The role of chronic inflammation in chronic
      dialysis-associated hypotension has not been investigated. A total of 38 dialysis
      patients with chronic hypotension were identified. Their demographic and
      biochemical data, inflammatory markers (high sensitivity C-reactive protein [hs
      CRP] and interleukin-6 [IL-6]), hepatocyte growth factor (HGF), leptin, and
      adiponectin levels were measured and compared with those of another 87
      nonhypotensive dialysis patients. No between-group differences in their clinical
      features, underlying renal disease were found. Levels of serum albumin, leptin,
      adiponectin, and HGF were similar between the two groups. The serum albumin
      levels were inversely correlated with hs-CRP and IL-6. Adiponectin was negatively
      correlated with hs-CRP and leptin. HGF showed a positive relation with hs-CRP. No
      association was found between adiponectin and HGF. Therefore, chronic
      inflammation is prevalent in the dialysis population, and serum HGF level is
      associated with inflammation but not with chronic dialysis hypotension.

PMID- 16305656
TI  - The 25th Anniversary Meeting of the American Society for Reproductive Immunology,
      Providence, RI, June 16-18, 2005.

PMID- 16305657
TI  - A review of trafficking and activation of uterine natural killer cells.
AB  - PROBLEM: Enrichment of uterine natural killer (uNK) cells occurs during pregnancy
      in many species. However, functions of uNK cells and regulation of their uterine
      homing are not fully defined. In mice and women, uNK cells contribute to
      angiogenesis, a role reviewed here and now addressed in a mammal with an
      alternative placental type. METHODS OF STUDY: To address lymphocyte functions,
      RNA from murine or porcine endometrium and lymphocytes purified from endometrium
      were analyzed using real-time or reverse transcription PCR. To address homing
      potential, human blood CD56(+) lymphocytes were evaluated using both RNA and
      functional adhesion to endothelium presented under shear force in frozen sections
      of gestation day 7 C57Bl/6J implantation sites. Women were serially sampled over
      a menstrual cycle or a clinical preparatory cycle for embryo transfer. RESULTS:
      Activation of murine uNK cells is associated with much greater increases in
      transcription for Eomes than for T-bet (Tbx21). Lymphocytes from normal porcine
      implantation sites transcribe vascular endothelial growth factor, placental
      growth factor, interferon-gamma and hypoxia-inducible factor (HIF)-1alpha. In
      fertile women, increases in L-selectin- and alpha4-integrin-mediated interactions
      between CD56(+) cells and endothelium occur at luteinizing hormone (LH) surge
      (cycling women) to oocyte pick up or embryo transfer, then return to pre-LH
      levels. CONCLUSIONS: Uterine lymphocytes may universally promote pregnancy
      associated endometrial angiogenesis. Recruitment of uNK precursor cells from
      blood appears to occur in a window promoted by rising plasma estrogen and LH and
      limited by rising progesterone.

PMID- 16305658
TI  - Antifertility effect of passive administration of antibodies to 80 kDa human
      sperm antigen and its synthetic peptides in male and female rats.
AB  - PROBLEM: A human sperm antigen of molecular size of about 80 kDa (80 kDa HSA) has
      been reported to be sperm-specific, conserved and responsible for inducing
      immunological infertility. The partial N-terminal amino acid sequence of 80 kDa
      HSA (peptide NT) and its peptides obtained by enzymatic digestion with
      endoproteinase Lys-C (peptides 1-4) and with endoproteinase Glu-C (peptides 5 and
      6) did not show sequence homology with any of the proteins of the GenBank. The
      peptides NT, 1, 2, 3 and 4 were synthesized, conjugated to keyhole limpet
      hemocyanin and used as an immunogen to raise the antibodies in rabbits. Peptide 3
      did not elicit significant antibody titer while peptides NT, 1, 2 and 4 elicited
      significant antibody titer and immunobiologically mimicked the native protein.
      METHOD OF STUDY: Effects of passive administration of two injections each of 200
      microL of antibodies or 10 and 40 microg purified immunoglobulins to 80 kDa HSA,
      peptides NT, 1, 2 and 4 on fertility in male and female rats were investigated.
      RESULTS: Passive administration of antibodies to 80 kDa HSA and its peptides NT,
      1, 2 and 4 resulted in agglutination of epididymal spermatozoa with loss of
      motility but had no effect on sperm count or weights of the reproductive organs.
      These animals failed to impregnate normal female rats. Passive administration of
      these antibodies to female rats also resulted in infertility. The presence of
      antibodies was detected by enzyme-linked immunosorbent assay in uterine
      secretions of animals treated with antipeptide antibody. The presence of
      agglutinated spermatozoa was observed in the post-coital vaginal smears of these
      animals. The immunized females were found to be ovulating normally and the number
      of corpora lutea were unaltered. Of the four antipeptide antibodies studied,
      antibodies to peptides NT and 1 were most effective in inhibiting fertility both
      in male as well as female rats. Hence, the antifertility studies were further
      confirmed by passive administration of 10 and 40 microg of purified
      immunoglobulins of antibodies to NT and 1, which resulted in a dose-dependent
      inhibition of fertility in male and female rats. CONCLUSIONS: The study
      demonstrated that the synthetic peptides of 80 kDa HSA immunobiologically
      mimicked the native protein and impaired fertility following passive
      administration of antipeptide antibodies and hence, suggested the suitability of
      synthetic peptides of 80 kDa HSA as candidates for development of antifertility
      vaccine.

PMID- 16305659
TI  - Characterization and partial purification of a macrophage-stimulating factor from
      Mycoplasma hominis.
AB  - PROBLEM: Mycoplasma hominis is one of the most common pathogens of the genital
      tract and is associated with increased production of proinflammatory cytokines in
      reproductive tissues during preterm labor. The mechanism by which M. hominis, an
      organism lacking cell walls, increases the production of proinflammatory
      cytokines is unknown. METHOD OF STUDY: We characterized and purified a macrophage
      activating factor from this organism. RESULTS: Extraction of whole organisms with
      Triton-X-114 demonstrated that the activity was primarily associated with the
      detergent phase. Macrophage-stimulating activity (MSA) of detergent extracts of
      M. hominis was not inhibited by polymyxin B or heating but was completely
      abrogated by alkaline hydrolysis and partially reduced by proteinase K digestion.
      Further experiments that utilized Toll-like receptor (TLR)-2- and TLR-4
      transfected cells, revealed that the detergent extracts activate TLR-2 but not
      TLR-4 signal transduction. Purification of the activity using preparative SDS
      PAGE and reverse phase chromatography experiments led to the isolation of a 29
      kDa protein. CONCLUSIONS: These experiments suggest that the MSA of M. hominis is
      due to a lipophillic factor that interacts with TLR-2 rather than TLR-4 (as does
      lipopolysaccharide), to increase tumor necrosis factor (TNF)-alpha by
      macrophages. It is known that TNF-alpha can cause preterm labor and intrauterine
      fetal death and that it is upregulated in amniotic fluid samples infected with M.
      hominis.

PMID- 16305660
TI  - Low erythrocyte complement receptor type 1 (CR1, CD35) expression in preeclamptic
      gestations.
AB  - PROBLEM: Erythrocyte complement receptor type 1 (E-CR1) is the main immune
      complex clearance mechanism in humans. Decreased E-CR1 expression is noted in
      certain inflammatory disorders. Recent evidence implicates inflammation in the
      pathogenesis of preeclampsia. We investigated whether E-CR1 is decreased in
      preeclampsia. METHOD OF STUDY: E-CR1 protein expression was quantified by
      radioimmunoassay. Plasma concentration of soluble CR1 was quantified using a
      specific enzyme linked immunosorbent assay. Quantitative genotypes were evaluated
      by HindIII restriction fragment length polymorphism analysis. RESULTS: E-CR1
      expression was reduced in patients with preeclampsia. Lack of neoantigen
      expression (indicative of enzymatic cleavage of CR1) or elevated plasma-soluble
      CR1 was evidence against an acquired loss of E-CR1. Genotype analysis revealed a
      higher frequency of a CR1 allele associated with low E-CR1 expression in
      preeclampsia when compared with normal pregnant controls. CONCLUSIONS: E-CR1
      expression is decreased in preeclamptic patients and levels correlate with
      severity of disease. This condition may have a genetic basis in some patients.

PMID- 16305661
TI  - Unraveling Brucella genomics and pathogenesis in immunocompromised IRF-1-/- mice.
AB  - PROBLEM: Brucellosis causes abortion in domestic animals and Malta fever in
      humans. Comparison of Brucella species genomes may reveal potential virulence
      mechanisms. Engineering bioluminescent Brucella would permit monitoring bacterial
      dissemination. METHOD OF STUDY: Microarray of the B. melitensis genome allowed
      comparison of gene content from six Brucella species. Bioluminescent B.
      melitensis strains were developed using transposon mutagenesis permitting the
      study of pathogenic Brucella in mice. Monitoring bacterial dissemination as well
      as organ localization permits evaluating the role of genes and genomic islands in
      mutant bacteria. RESULTS: Comparative genomic analysis revealed 217 ORFs altered
      in five Brucella species and were often found in islands. Bioluminescent bacteria
      disseminated from the injection site to liver, spleen, inguinal lymph nodes,
      testes and submanibular region. CONCLUSIONS: Genomic islands contribute to
      Brucella pathogenicity. Biophotonic imaging suggests that Brucella dissemination
      in mice parallels acute and chronic infections of humans.

PMID- 16305662
TI  - Regulatory T cells in ovarian cancer: biology and therapeutic potential.
AB  - Tumors express tumor-associated antigens (TAA) and thus should be the object of
      immune attack. Nonetheless, spontaneous clearance of established tumors is rare.
      Much work has demonstrated that tumors have numerous strategies either to prevent
      presentation of TAA, or to prevent TAA presentation in the context of T-cell co
      signaling molecules. Thus, it was thought that lack of TAA-specific immunity was
      largely a passive process: tumors simply did not present enough TAA, or antigen
      presenting cells did not have sufficient stimulatory capacity. On this basis,
      attempts were made to bolster TAA-specific immunity by using optimal antigen
      presenting cells or by growing TAA-specific effector T cells ex vivo followed by
      adoptive transfer. These approaches met with some success in mouse models of
      human tumors, and showed some early clinical efficacy in human trials, although
      long-term efficacy remains to be established, and logistical problems are
      considerable. These studies established the concept that experimentally induced
      TAA-specific immunity is a rational and potentially efficacious means to treat
      cancer, including ovarian cancer. Nonetheless, recent work demonstrates that lack
      of naturally induced TAA-specific immunity is not simply a passive process. We
      discuss recent data clearly demonstrating that 'tumors actively prevent induction
      of TAA-specific immunity through induction of TAA-specific tolerance'. This
      tolerance is mediated in part by regulatory T cells (Tregs). Means to revert
      these tolerizing conditions represent a novel anticancer therapeutic stratagem.
      We discuss Tregs in this regard in human ovarian cancer and present evidence that
      depleting Treg in human cancer, including ovarian cancer, using denileukin
      diftitox (Ontak), improves immunity and may be therapeutic.

PMID- 16305663
TI  - Antisperm vaccine for contraception.
AB  - PROBLEM: This study is a review of antisperm contraceptive vaccine (CV)
      development with the main focus on research going on in our laboratory. METHOD OF
      STUDY: Various methods of proteomics and genomics, hybridoma technology,
      substractive libraries, differential display method, and phage display technology
      were used to obtain sperm-specific genes and proteins. The present study will
      primarily focus on the sequences obtained by using the phage display technology
      and their role in CV development and human immunoinfertility. RESULT: Four novel
      peptides, delineated by using the phage display technology, were found to be
      involved in human immunoinfertility. The vaccine based on one of these peptides,
      designated as YLP(12), caused a reversible contraception in female mice.
      CONCLUSIONS: The vaccine targeting sperm is a feasible and exciting approach to
      contraception. The phage display technology is a powerful tool to delineate sperm
      specific peptide sequences that can be used for the CV development and in the
      diagnosis and treatment of infertility mediated through antisperm antibodies.

PMID- 16305664
TI  - Pre-eclampsia is not associated with changes in the levels of regulatory T cells
      in peripheral blood.
AB  - PROBLEM: The acceptance of the semi-allogeneic fetus within the maternal
      environment requires tolerance mechanisms not fully characterized yet. Normal
      pregnancy is known to be associated with a Th2 profile. Furthermore, regulatory T
      cells (Tregs) were proposed to regulate the Th2/Th1 balance at early stages of
      pregnancy. Treg may avoid the shift to a Th1 profile, thus preventing
      miscarriage. Accordingly, spontaneous abortion is characterized by a Th1
      dominance and diminished levels of Treg. The major aim of the present work was to
      investigate if pre-eclampsia, a late immunological complication of pregnancy, is
      characterized by similar hallmarks. METHOD OF STUDY: We measured the surface
      antigens CD4, CD25, CD8 and CTLA4 in peripheral blood from patients suffering
      from pre-eclampsia (n = 8) and age-matched patients undergoing normal pregnancies
      (n = 9) by four-color flow cytometry. RESULTS: We were not able to find any
      significant differences in the levels of CD4(+), CD25(+), CD8(+), CTLA4,
      CD4(+)/CD25(+), CD4(+)/CD25(bright), CD4(+)/CTLA4, CD25(+)/CTLA4,
      CD4(+)/CD25(+)/CTLA4, CD8(+)/CD25(+), CD8(+)/CTLA4 or CD8(+)/CD25(+)/CTLA4 cell
      subsets. CONCLUSIONS: Our data confirm comparable number of Tregs during pre
      eclampsia and normal pregnancy in peripheral blood. Other regulatory mechanisms
      might be involved during late pregnancy.

PMID- 16305665
TI  - Update on treatment of immunologic abortion with low-dose intravenous
      immunoglobulin.
AB  - PROBLEM: Recurrent spontaneous abortion associated with immunologic abnormalities
      has been termed immunologic abortion. Previously we showed that treatment with
      low-dose intravenous immunoglobulin (IVIG) appears to be beneficial for older
      women with immunologic abortion. We now report the results of IVIG treatment in a
      larger group of women with this disorder. METHOD OF STUDY: A total of 99 women
      were prospectively evaluated for immunologic abortion, which was defined as three
      or more miscarriages and the presence of specific immunologic abnormalities.
      Prior to the next conception, patients were treated with IVIG at a dose of 0.2
      g/kg. Once conception was achieved, IVIG treatment was continued on a monthly
      basis through 26-30 weeks of pregnancy. RESULTS: The average age of the women was
      37 years (range: 28-49), and the average number of miscarriages was 3.8 (range: 3
      12). Of the 99 women, 72 received initial IVIG treatment, and 50 subsequently
      became pregnant. Of these women, 42 (84%) had a successful term pregnancy. Of the
      27 women who refused IVIG therapy, 20 became pregnant and 18 (90%) miscarried.
      The difference in pregnancy success rate between the IVIG-treated and untreated
      groups was significant (P = 0.001). Four women had mild allergic reactions during
      IVIG infusion, and these reactions resolved when the IVIG brand was changed.
      Fetal abnormalities were not observed. CONCLUSION: We conclude that low-dose IVIG
      therapy is safe and effective for older women with immunologic abortion.

PMID- 16305666
TI  - Physiology should be supported with evidence in progesterone administration for
      threatened miscarriage -- authors' reply.

PMID- 16305668
TI  - Are yeasts free-living unicellular eukaryotes?
AB  - Yeasts are defined as unicellular fungi, yet many recent observations suggest
      their whole lifestyle is anything but unicellular. This review surveys the
      evidence that yeasts are really social organisms with cell-to-cell communication.

PMID- 16305669
TI  - Thermal tolerance of acid-adapted and unadapted Salmonella, Escherichia coli
      O157:H7, and Listeria monocytogenes in cantaloupe juice and watermelon juice.
AB  - AIMS: A study was performed to determine D values of acid-adapted and unadapted
      cells of Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes in
      cantaloupe juice and watermelon juice. METHODS AND RESULTS: Salmonella enterica
      serotype Poona, S. enterica serotype Saphra, two strains of E. coli O157:H7, and
      two strains of L. monocytogenes were grown in tryptic soy broth (TSB) and TSB
      supplemented with 1% glucose for 24 h at 37 degrees C. Decimal reduction times (D
      values) of cells suspended in unpasteurized cantaloupe juice and watermelon juice
      were determined. Acid-adapted cells of Salmonella and E. coli O157:H7, but not L.
      monocytogenes, had increased thermal tolerance compared with cells that were not
      acid-adapted. There was no correlation between soluble solids content of the two
      types of juice and thermal resistance. CONCLUSIONS: Growth of Salmonella and E.
      coli O157:H7 in cantaloupe juice, watermelon juice, or other acidic milieu,
      either in preharvest or postharvest environments, may result in cross protection
      to heat. The pasteurization conditions necessary to achieve elimination of
      pathogens from these juices would consequently have to be more severe if cells
      are habituated to acidic environments. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Insights from this study provide guidance to developing pasteurization processes
      to eliminate Salmonella, E. coli O157:H7, and L. monocytogenes in cantaloupe
      juice and watermelon juice.

PMID- 16305670
TI  - Isolation of culturable yeasts from market wines and evaluation of the 5.8S-ITS
      rDNA sequence analysis for identification purposes.
AB  - AIMS: To test the possibility that wines available in the marketplace may contain
      culturable yeasts and to evaluate the 5.8S-ITS rDNA sequence analysis as adequate
      means for the identification of isolates. METHODS AND RESULTS: As a case study,
      typical Greek wines were surveyed. Sequence analysis of the 5.8S-ITS rDNA was
      tested for its robustness in species or strain identification. Sixteen isolates
      could be assigned into the species Brettanomyces bruxellensis, Saccharomyces
      cerevisiae and Rhodotorula pinicola, whereas four isolates could not be safely
      identified. B. bruxellensis was the dominant species present in house wines,
      while non-Saccharomyces sp. were viable in aged wines of high alcohol content.
      CONCLUSIONS: Yeast population depends on postfermentation procedures or storage
      conditions. Although 5.8S-ITS rDNA sequence analysis is generally a rapid method
      to identify wine yeast isolates at the species level, or even below that, it may
      not be sufficient for some genera. SIGNIFICANCE AND IMPACT OF THE STUDY: This is
      the first report to show that commercial wines may possess diverse and
      potentially harmful yeast populations. The knowledge of yeasts able to reside in
      this niche environment is essential towards integrated quality assurance
      programmes. For selected species, the 5.8S-ITS rDNA sequence analysis is a rapid
      and accurate means.

PMID- 16305671
TI  - Antimicrobial activity of a nisin-activated plastic film for food packaging.
AB  - AIMS: To determine the effectiveness of a packaging film coated with nisin to
      inhibit Micrococcus luteus ATCC 10240 in tryptone soya broth (TSB) and the
      microbiota of raw milk during storage. A further aim was to examine the release
      of nisin from the activated film. METHODS AND RESULTS: An active package,
      obtained from nisin-treated film, was filled with 1 l of M. luteus ATCC 10240
      (ML) suspension in TSB and stored at 4 and 25 degrees C for 2 days. After 24 h at
      25 degrees C there was a remarkable reduction of M. luteus ATCC 10240 compared
      with the control, while at 4 degrees C a slight reduction was observed. Moreover,
      microbial growth was controlled when 1 l of three different kinds of milk was
      poured into the active package and stored at 4 degrees C for 7 days. The most
      significant results were observed in raw milk and pasteurized milk with a
      reduction of 0.9 log and 1.3 log, respectively. The release experiments showed
      that nisin release from the film was unpredictable, but it was favoured by low pH
      and high temperature. CONCLUSIONS: It appears that nisin-coated films were
      effective in inhibiting M. luteus ATCC 10240 in TSB and the bacterial flora in
      milk, and the release of nisin was pH and temperature dependent. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Nisin-activated film may control bacterial growth,
      maintaining food quality, safety and extending the shelf-life of food products.

PMID- 16305672
TI  - Detection of Legionella pneumophila in water samples by species-specific real
      time and nested PCR assays.
AB  - AIMS: Legionella pneumophila is a contaminant of man-made water systems,
      including potable water, cooling towers, water systems of large buildings, etc.
      It is the most common causative agent of legionellosis, a respiratory infection,
      which may give rise to restricted outbreaks. To survey environmental water
      samples from hospitals and private habitations in Bologna, we developed a species
      specific nested and a TaqMan real-time PCR for the detection of L. pneumophila.
      We compared the two assays and both to cultural isolation. METHODS AND RESULTS:
      The targeted gene was macrophage infectivity potentiator (mip), conserved in L.
      pneumophila, and divergent in other legionellae. One assay was based on a nested
      PCR and the other on a TaqMan real-time PCR protocol. Their sensitivities were 14
      % or 5% higher than that of cultural isolation respectively. The detection limits
      were 1-2 genome equivalents per 50-microl reaction. Specificity was assessed
      using DNA from nine target and 20 nontarget organisms. CONCLUSIONS: When applied
      to water samples, both assays detected L. pneumophila at 80% or higher frequency.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The species-specific molecular diagnosis of
      L. pneumophila by means of nested PCR does not require a specific
      instrumentation, exhibits a high sensitivity, and is advantageous over the
      cultural isolation and real-time PCR detection. It allows to quickly monitor
      water samples for the risk assessment of environmental contaminations.

PMID- 16305673
TI  - Triclosan-bacteria interactions: single or multiple target sites?
AB  - AIMS: To investigate the inhibitory and lethal effects of triclosan against
      several micro-organisms at different stages of their phase of population growth.
      METHODS AND RESULTS: Triclosan minimum inhibitory concentrations against several
      test organisms were determined in broth and agar using standard protocols. The
      bisphenol effect on bacterial population growth kinetics was studied using the
      Bioscreen C microbial growth analyser. Finally, the efficacy of triclosan on
      phases of bacterial growth was determined using a standard suspension test. The
      duration of the lag phase for all micro-organisms tested was increased by
      bisphenol in a concentration-dependent manner. The population growth kinetics of
      the micro-organisms was also altered after biocide exposure. At higher
      concentrations, triclosan was bactericidal regardless of their phase of
      population growth, although population in stationary phase and particularly,
      washed suspensions, were more resilient to the lethality of triclosan. This
      lethal activity was concentration and contact time dependent, and in some
      instances, bactericidal activity of bisphenol was observed within 15 s.
      CONCLUSIONS: Low concentrations of triclosan affected the growth of several
      bacteria, while higher concentrations were bactericidal regardless of the
      bacterial phase of population growth. SIGNIFICANCE AND IMPACT OF THE STUDY: Here,
      we presented clear evidence that the interaction of triclosan with the bacterial
      cell is complex and its lethality cannot be explained solely by the inhibition of
      metabolic pathways such as the enoyl acyl-reductase. However, the inhibition of
      such pathways cannot be ruled out as part of the lethal mechanism of the
      bisphenol at a low bactericidal concentration.

PMID- 16305674
TI  - Isolation and characterization of two anti-staphylococcal bacteriophages specific
      for pathogenic Staphylococcus aureus associated with bovine infections.
AB  - AIMS: The aim of this study was to isolate and characterize bacteriophages
      against bovine Staphylococcus aureus associated with mastitis. METHODS AND
      RESULTS: We describe the isolation of two anti-staphylococcal phages namely DW2
      and CS1 from farmyard slurry. Both phages were characterized by electron
      microscopy and restriction analysis and shown to belong to the Siphoviridae
      family. CS1 and DW2 were lytic for representatives of all three clonal groups of
      Irish mastitis-associated staphylococci. These phages were compared with the
      previously characterized Myoviridae phage K. Infusion of a cocktail of all three
      phages at 10(8) PFU ml(-1) into live cow teats resulted in no detectable increase
      in somatic cell counts in milks indicating that the phages did not irritate the
      animal. CONCLUSION: Two new anti-staphylococcal phages CS1 and DW2 were isolated
      and characterized and tested for immunogenicity in animal teats. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The phages isolated in this study are active against
      pathogenic S. aureus and may be incorporated into teat-dips or teat-washes as a
      non-antibiotic prophylaxis against staphylococcal bovine mastitis.

PMID- 16305675
TI  - Resuscitation of acid-injured Salmonella in enrichment broth, in apple juice and
      on the surfaces of fresh-cut cucumber and apple.
AB  - AIMS: To investigate the resuscitation of acid-injured Salmonella enterica in
      selected enrichment broths, in apple juice and on cut surfaces of apple and
      cucumber slices. METHODS AND RESULTS: Following exposure to 2.4% acetic acid for
      7 min, S. enterica (serovars Mbandaka, Chester and Newport) cells were used to
      inoculate enrichment broths, phosphate-buffered saline (PBS), apple juice and
      fruit slices. Injured Salmonella cells resuscitated and regained the ability to
      form colonies on selective agar (Xylose-Lysine-Tergitol 4) if they were incubated
      in lactose broth (LB), universal pre-enrichment broth (UPB) or buffered peptone
      water (BPW), but not in tetrathionate broth, PBS or apple juice. The
      resuscitation occurred at a significantly (P > 0.05) faster rate in UPB than in
      LB or BPW. The resuscitation also occurred on the surfaces of fresh-cut cucumber
      at 20 degrees C, but not at 4 degrees C. CONCLUSIONS: Acid-injured Salmonella
      cells resuscitated in nonselective enrichment broths at different rates, but not
      in selective enrichment broth, apple juice, PBS or on fresh-cut apple.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Pre-enrichment of food samples in UPB prior
      to selective enrichment is recommended. Injured Salmonella cells have the ability
      to resuscitate on fresh-cut surfaces of cucumber when stored at abusive
      temperatures.

PMID- 16305676
TI  - Release studies of Lactobacillus casei strain Shirota from chitosan-coated
      alginate-starch microcapsules in ex vivo porcine gastrointestinal contents.
AB  - AIMS: To investigate the release characteristics of Lactobacillus casei strain
      Shirota (LCS) from chitosan-coated alginate-starch (CCAS) capsule in different
      regions of ex vivo porcine gastrointestinal (GI) contents. METHODS AND RESULTS: A
      0.1 g of CCAS encapsulated bacteria (containing c. 10(8) CFU of LCS) were
      incubated in different sections of ex vivo porcine GI contents (10 ml)
      anaerobically at 37 degrees C. Samples were taken from different GI contents at
      different time intervals (up to 24 h) and estimated for the release of LCS from
      capsules. There was almost a complete release (1.1 x 10(8) CFU) of LCS from
      capsules within 8 h of incubation in ileal contents, while it took nearly 12 h to
      release the completely encapsulated bacteria in colon content under similar
      conditions. There was only a partial release of encapsulated LCS, incubated in
      duodenal and jejunal contents, while there was no significant (P > 0.05) release
      of encapsulated bacteria in gastric contents even after 24 h of incubation.
      CONCLUSIONS: The capsules were able to release viable probiotic cells completely
      in ex vivo porcine ileal and colon contents. SIGNIFICANCE AND IMPACT OF THE
      STUDY: CCAS capsule can be an effective way of protecting probiotic bacteria from
      adverse gastric conditions and delivering viable bacteria to the host intestinal
      systems.

PMID- 16305677
TI  - l-leucine aminopeptidase production by filamentous Aspergillus fungi.
AB  - AIMS: To screen various filamentous fungi belonging to Aspergillus spp. producing
      leucine and methionine aminopeptidases. METHODS AND RESULTS: Twenty-eight
      Aspergillus strains representing 14 species within the genus were screened for L
      leucine aminopeptidase (LAP) production in two media in shake flask fermentation.
      Two Aspergillus sojae (NRRL 1988 and NRRL 6271) and one Aspergillus oryzae (NRRL
      6270) strains were selected as the best producers for further studies. The peak
      LAP activities were 2.61, 2.59 and 1.30 IU ml(-1) for the three fungi on days 2,
      5 and 4 respectively. In addition to LAP, L-methionine aminopeptidase (MAP)
      activity was also detected. Apart from submerged fermentation, the highest LAP
      yields by solid-state fermentation were 11.39, 17.40 and 13.02 IU g(-1) dry
      matter for the above fungi. The temperature and pH optimum of the enzyme was
      found to be in the range of 65-75 degrees C at pH 8.0-9.0 for all three fungi.
      Metal ions, Co(2+) and Fe(2+) in 2 mmol l(-1) concentration apparently enhanced
      the relative enzyme activity and heat stability. CONCLUSIONS: Two A. sojae (NRRL
      1988 and NRRL 6271) and one A. oryzae (NRRL 6270) strains were found to be the
      best producers of LAP and MAP. The preliminary characterization studies revealed
      that the enzyme is considerably thermostable and belongs to the class
      metalloenzymes. SIGNIFICANCE AND IMPACT OF THE STUDY: A good number of aspergilli
      were screened and the ability of the fungal aminopeptidase to release a
      particular N-terminal amino acid along with its high thermal stability, makes
      them interesting for controlling the degree of hydrolysis and flavour development
      for a wide range of substrate.

PMID- 16305678
TI  - A simple cultural method for the presumptive detection of the yeasts
      Brettanomyces/Dekkera in wines.
AB  - AIMS: The development of a simple and reliable procedure, compatible with routine
      use in wineries, for the presumptive detection of Brettanomyces/Dekkera from wine
      and wine-environment samples. METHODS AND RESULTS: The method of detection of
      these yeasts employs a selective enrichment medium. The medium contains glucose
      (10 g l(-1)) as carbon and energy source, cycloheximide (20 mg l(-1)) to prevent
      growth of Saccharomyces, chloramphenicol (200 mg l(-1)) to prevent growth of
      bacteria and p-coumaric acid (20 mg l(-1)) as the precursor for the production of
      4-ethyl-phenol. After the inoculation with wine, the medium is monitored by
      visual inspection of turbidity and by periodic olfactive analysis. Contaminated
      wines will develop visible turbidity in the medium and will produce the 4-ethyl
      phenol off-odour, which can be easily detected by smelling. CONCLUSIONS: A
      selective enrichment liquid medium was developed to differentially promote the
      growth and activity of Brettanomyces/Dekkera. The method is simple to execute,
      employing a simple-to-prepare medium and a periodic olfactive detection.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The characteristics of the procedure make
      it particularly applicable in a wine-making environment thus presenting important
      advantages to the wine industry.

PMID- 16305679
TI  - Nomenclature for factors of the swine leukocyte antigen class II system, 2005.
AB  - A systematic nomenclature for the genes and alleles of the swine major
      histocompatibility complex (MHC) is essential to the development and
      communication of research in swine immunology. The Swine Leukocyte Antigen (SLA)
      Nomenclature Committee of the International Society for Animal Genetics (ISAG)
      has reviewed all of the DNA-sequence information for MHC class II genes,
      available in GenBank/EMBL/DDBJ databases, and the associated published reports to
      develop such a systematic nomenclature. This article summarizes the proposed
      nomenclature, which parallels the World Health Organization's nomenclature for
      factors of the human MHC. The SLA class II genes expressed on the cell membrane
      will be noted as SLA-DRA, SLA-DRB1, SLA-DQA, and SLA-DQB1. Nomenclature
      assignments for all SLA class II GenBank sequences are now noted. The committee
      will add new SLA class II allele designations, as they are discovered, and will
      maintain a publicly available list of all recognized genes and alleles using the
      Immuno Polymorphism Database (IPD). The sequences will be available from the IPD
      MHC section of the database which contains non-human MHC sequences
      (http://www.ebi.ac.uk/ipd/mhc/sla/).

PMID- 16305680
TI  - Identification of five different IGHV gene families in owl monkeys (Aotus
      nancymaae).
AB  - In order to characterize immunoglobulin heavy-chain variable (IGHV) genes in
      Aotus nancymaae monkeys, different mRNAs encoded by five IGHV families in this
      non-human primate were molecularly analysed considering their paramount
      importance in antibody production in an immune response. This study reports gene
      products exhibiting 91% amino acid similarity with IGHV1, IGHV2, IGHV3, IGHV4 and
      IGHV7 human IGHV families. Our analyses suggest that the IGHV gene has several
      conserved characteristics in humans and A. nancymaae. Several amino acid residues
      that are highly conserved in all family members described in humans were also
      present in these families in A. nancymaae. Antibody diversity in these families
      has remained the same since divergence of both species. Our study continues to
      provide evidence supporting the use of A. nancymaae monkey as an animal model for
      studying antibody response.

PMID- 16305681
TI  - A new PCR-SSP typing method for six single-nucleotide polymorphisms impairing the
      blood-clotting cascade as well as T-cell stimulation.
AB  - Single-nucleotide polymorphisms (SNPs) within the genes of factor V (FV) (G1691A;
      exon 10), prothrombin (FII) (G20210A; 3'untranslated - region) and
      methylenetetrahydrofolate reductase (MTHFR) (C677T; exon 4) are associated with
      hypercoagulability, and systematic screening of individuals being at higher risk
      of thrombosis has been suggested. SNPs in the 2q33 region within the genes of
      CD28 (+17T/C; intron 3) and CTLA4 (-318C/T; promoter and +49A/G; exon 1) are
      likely to affect T-cell proliferation and antigen presentation signaling, which
      may lead to altered sensitivity of allograft or self-tissue recognition and
      affect the incidence of autoimmune diseases. We developed primers that allow
      specific amplification of these six SNPs at test conditions identical with those
      used for HLA typing with the CTS PCR-SSP reagents. One hundred ninety-six healthy
      German Caucasian individuals were tested for the six SNPs. The genotype
      frequencies for all SNPs were in Hardy-Weinberg equilibrium. There was no
      significant difference in the distribution of genotypes when compared to other
      published studies in which these SNPs were tested. The described PCR-SSP method
      can be used to screen large numbers of patients for these SNPs.

PMID- 16305682
TI  - Uveodermatologic (VKH-like) syndrome in American Akita dogs is associated with an
      increased frequency of DQA1*00201.
AB  - The Akita breed of dog is affected by a number of distinct immune-mediated
      diseases, including thyroiditis, sebaceous adenitis, pemphigus foliaceus,
      uveitis, polyarthritis, myasthenia gravis, and uveodermatologic (UV) syndrome. UV
      syndrome is manifested by progressive uveitis and depigmenting dermatitis that
      closely resembles the human Vogt - Koyanagi - Harada syndrome. This study
      examined the allelic diversity of the three DLA class II loci (DRB1, DQA1, and
      DQB1) in the American Akita dog, and the relationship of specific DLA class II
      alleles to the UV. Low allelic variation was demonstrated within genes of DLA
      class II. American Akita dogs possessed six of the reported 16 DQA1 alleles, but
      only eight of 61 reported alleles in DRB1 and nine of 47 reported alleles in
      DQB1. Almost one-half of American Akita dogs were homozygous for a single allele
      at DQA1 and up to a quarter at DRB1 and DQB1. DLA-DQA1*00201 was associated with
      a significantly higher relative risk (RR = 15.3) or odds ratio (OR = 15.99) for
      UV syndrome than other DLA class II alleles. No significant association was noted
      with haplotypes of DRB1, DQB1, and DQA1 alleles; DRB1*03201-DQA1*00201 trended
      toward significance. This study confirmed loss of DLA genetic diversity in the
      American Akita dog in common with other pure breeds of dog and suggested a role
      for certain DLA class II gene alleles in the pathogenesis of UV.

PMID- 16305683
TI  - HLA-A and HLA-B allele frequencies in a mestizo population from Guadalajara,
      Mexico, determined by sequence-based typing.
AB  - HLA-A and HLA-B genes were typed by DNA sequencing in a mestizo population from
      Guadalajara, Jalisco, Mexico. Thirty-seven HLA-A and 51 HLA-B alleles were
      observed in 103 samples. The common typical Amerindian alleles (>5%) and
      haplotypes (>or=2.0%) found were A*02010101, *24020101, *310102, B*350101, and
      *4002, and A*310102-B*4002, A*240201-B*350101, and the typical European alleles
      were A*010101, *29010101, B*1402, B*180101, and A*020101-B*1402, A*020101
      B*510101, and A*3002-B*180101. This reflects the blending of the two main
      parental populations of mestizos: Amerindian and Iberian. Mexicans were found to
      be relatively closer to the Portuguese than to Spaniards. This proximity may
      indicate a larger Portuguese influence in Mexicans than previously considered.
      Present data contribute to the understanding of the genetic structure in Mexico.

PMID- 16305684
TI  - Analysis of evolutionary conservation in CD1d molecules among primates.
AB  - The hereditary conservation in the genetically encoded CD1D sequences of various
      primates was analyzed. Genomic CD1D sequences of 17 rhesus macaques with distinct
      origins, eight Indian and nine Chinese, were examined and differences of only one
      or two nucleotides were detected and the consensus sequence of rhesus CD1D was
      determined. CD1D consensus sequences of three African green monkeys (AGMs) and
      the rhesus monkeys were then compared to study the evolutionary differences among
      interspecies. The CD1D consensus sequence determined from AGMs apparently
      differed by seven nucleotides from the rhesus consensus sequence, and nucleotide
      difference induced only three amino acid changes within Exon3, corresponding to
      the alpha2 domain of CD1d having a hydrophobic ligand-binding pocket. Such
      changes in the alpha2 domain may alter the characteristics of the SIV-derived
      glycolipid/lipid antigens presented by each CD1d molecule to innate natural
      killer T cells. In addition, the CD1D genomic sequences of three chimpanzees
      (chimps) were determined. To our surprise, although Exon2 and Exon3 reflecting
      antigen-binding alpha1 and alpha2 domains in chimps' CD1D were identical to that
      in humans except one amino acid, three amino acids within Exon4, reflecting
      alpha3 domain, were distinct from humans, and one of them was identical to those
      in rhesus and AGM CD1D. On the basis of the findings, the evolutionary
      relationship of the CD1d molecules among the various primates and their HIV-1/SIV
      susceptibility will be discussed.

PMID- 16305685
TI  - Polymorphisms of chemokine receptors and eNOS in Brazilian patients with sickle
      cell disease.
AB  - Sickle cell disease (SCD) is an inherited disorder that presents extremely
      variable clinical manifestations. For the past few decades, it has been
      approached as an inflammatory disorder, and several researchers have tried to
      determine the factors involved in such characteristic. In order to contribute to
      the identification of the genetic differences underlying this phenotypic
      diversity in SCD, we proposed to study the distribution of polymorphic variants
      of the genes encoding the chemokine receptors CCR2 and CCR5, as well as three
      polymorphisms in the NOS3 gene, in Brazilian SCD patients. These genes are
      involved in the development of inflammatory immune reactions, a feature believed
      to be of extreme importance in SCD pathology. Our results indicate that the
      polymorphisms studied here are not directly associated with severe clinical
      manifestations in SCD patients. Nevertheless, we observed a tendency for the
      development of a severe clinical course in carriers of the variant alleles CCR2
      64I and CCR5delta32 and in homozygotes for the -786C variant of the NOS3 gene.
      Further studies should be carried out in order to assess the role of such
      variants in the clinical picture of SCD.

PMID- 16305686
TI  - HLA analysis of the Parsi (Zoroastrian) population in Pakistan.
AB  - The Parsis of Pakistan are descendants of Zoroastrians from Iran who fled to
      Gujarat in India after the Arab invasion in 900 AD. A small group eventually
      migrated from India to Karachi in Pakistan. In this study, the Parsis from
      Pakistan were analyzed at the HLA-B, -C, -DRB1 and -DQB1 loci using the
      polymerase chain reaction with sequence-specific primers (PCR-SSP). The most
      common alleles at the HLA loci were HLA-B*35 (15.9%), HLA-Cw*0602 (21.4%), HLA
      DRB1*11 (23.0%), and HLA-DQB1*02 (24.7%). Data analysis suggests that the Parsis
      of Pakistan and India descended from the same stock and may have the closest
      ancestry with Jewish and Italian populations.

PMID- 16305687
TI  - Identification of a new HLA-B allele, HLA-B*4443, in a German family.
AB  - A novel human leukocyte antigen (HLA)-B allele is described. The allele was
      identified in a German blood donor of Caucasian origin. Because high-resolution
      HLA-typing using sequence-specific primers gave inconclusive results, sequence
      based typing was performed. Nucleotide sequences of exons 2 and 3 most closely
      match with HLA-B*4417 and HLA-B*440301 (99.5% identity). The predicted protein
      sequence revealed a single amino acid substitution (D156L) compared with the HLA
      B*4417 allele but two substitutions (Y113H, D116S) compared with the HLA-B*440301
      allele. Therefore, the novel allele has been officially assigned HLA-B*4443 by
      the WHO Nomenclature Committee. The HLA-B*4443 allele was found with the A*2301,
      Cw*0401, B*4443, DRB1*0701, DRB4*0107, and DQB1*0202 haplotype.

PMID- 16305688
TI  - Description of a new HLA-DRB1*1104, DRB1*110403.
AB  - We report here the exon 2 sequence of the novel HLA-DRB1*110403 which differs
      from DRB1*110401 by a single synonymous nucleotide substitution at codon 78,
      where TAC is substituted by TAT. The variant originally identified in a Caucasoid
      individual was confirmed by cloning and sequencing.

PMID- 16305689
TI  - A novel HLA-B*270509 variant escaping detection by PCR-SSO-based histotyping.

PMID- 16305690
TI  - An amino acid contributing to pockets A, B, and D of the peptide-binding groove
      is altered in A*0315.

PMID- 16305691
TI  - A novel HLA-A*2601 variant, A*260102, identified by sequence-based typing.

PMID- 16305692
TI  - Identification of a novel HLA-B*4061 allele in the Chinese population.

PMID- 16305693
TI  - Novel HLA-Cw*01 allele, Cw*0111, identified by sequence-based typing.

PMID- 16305694
TI  - Structural aspect of B*4811 molecule, a novel HLA-B*48 allele identified by
      sequence-based typing.

PMID- 16305696
TI  - Association of the C677T methylenetetrahydrofolate reductase mutation with
      congenital heart diseases.
AB  - BACKGROUND: To investigate whether the cytosine-to-thymine mutation at base 677
      of the gene for methylenetetrahydrofolate reductase (MTHFR) is associated with
      congenital heart diseases (CHD), using high throughput heteroduplex analysis
      based upon the powerful technique of denaturing high-performance liquid
      chromatography. METHODS: We investigated the MTHFR genotype of a cytosine-to
      thymine mutation at base 677 for 213 patients of CHDs as confirmed by cardiac
      catheterization and also for 195 healthy controls. RESULTS: The overall genotype
      frequencies of the MTHFR C677T polymorphism were not significantly different
      between the CHD patients and the healthy control (P = 0.345). Furthermore, taking
      various subgroups of CHD patients into consideration, we noted a significantly
      increased proportion of homozygous TT genotypes for patients suffering from
      valvular pulmonary stenosis (PS) or pulmonary atresia with an intact ventricular
      septum (PA + IVS) (p = 0.0005). For patients revealing heterotaxy syndrome, a
      conotruncal anomaly including tetralogy of Fallot, an interruption of the aortic
      arch, persistent truncus arteriosus, and aortopulmonary window, no statistically
      significant difference existed. CONCLUSIONS: The discrepancy in the distribution
      of MTHFR genotypes amongst various subtypes of CHD reflects some heterogeneity in
      the developmental mechanism of CHD. The increased percentage of homozygous TT
      genotypes might contribute to the pathogenesis of valvular PS and PA + IVS.

PMID- 16305697
TI  - Increased granulocyte chemotactic protein-2 concentrations in peritoneal fluid of
      women with endometriosis.
AB  - BACKGROUND: To evaluate the release of granulocyte chemotactic protein-2 (GCP-2)
      into peritoneal fluid in women with endometriosis, we measured its concentration
      with reference to the disease stage and the phase of the menstrual cycle.
      METHODS: Surgery was scheduled in the proliferative or secretory phase of the
      menstrual cycle for 64 women with endometriosis (n = 38) or cystadenomas (n =
      26). GCP-2 concentrations in the peritoneal fluid were measured using an enzyme
      linked immunosorbent assay. RESULT: Our findings indicated elevated
      concentrations of GCP-2 in peritoneal fluid from women with endometriosis during
      the proliferative phase, which were positively correlated with the stage of
      endometriosis. CONCLUSION: Inflammation associated with endometriosis may be
      involved in the pathogenesis of the disease through increasing levels of
      peritoneal fluid GCP-2.

PMID- 16305698
TI  - A study of oligosaccharide variants of alpha-fetoproteins produced by normal
      fetuses and fetuses with trisomy 21.
AB  - BACKGROUND: The mechanisms of the increase in the percentage of alpha
      fetoproteins (AFPs) that strongly binds to Lens culinaris agglutinin (AFP-L3) in
      pregnancies with a trisomy 21 fetus have not been analyzed. To investigate the
      oligosaccharide variants of AFP produced by normal fetuses and fetuses with
      trisomy 21, the lectin reactivity of AFP was analyzed. METHODS: Fetal liver
      tissue, amniotic fluid, and maternal serum were obtained from five normal
      pregnancies and five pregnancies with a trisomy 21 fetus. The percentages of AFP
      reactive to lectins were determined by lectin-affinity electrophoresis coupled
      with antibody-affinity blotting. RESULTS: The percentages of AFP-L3 in the fetal
      liver and the maternal serum were 23.9 and 27.0%, respectively, in normal
      pregnancies, and 28.7 and 38.5%, respectively, in pregnancies with a trisomy 21
      fetus. There was no statistically significant difference between the percentage
      in the fetal liver and the percentage in the maternal serum in normal
      pregnancies; however, a significant difference (P < 0.01) was found in
      pregnancies with a trisomy 21 fetus. In regard to the percentage of AFP-L3 in the
      fetal liver, there was no significant difference; however, a significant
      difference (P < 0.05) was found in the maternal serum between normal pregnancies
      and pregnancies with a trisomy 21 fetus. CONCLUSIONS: The transference of the AFP
      L3 fraction might be relatively high in the placentas of women carrying a trisomy
      21 fetus, and this could be the one of the reasons for the increase in the
      percentage of AFP-L3 in the maternal serum in pregnancies with a trisomy 21
      fetus.

PMID- 16305699
TI  - Response of pregnancy leg edema to a single immersion exercise session.
AB  - BACKGROUND: To quantify the effect of a single immersion exercise session on
      uncomplicated dependent edema in pregnancy. METHODS: Lower leg volume was
      measured by water displacement volumetry and limb circumference in nine women
      with marked dependent edema, but otherwise normal second or third trimester
      pregnancy, before and after upright water immersion exercise session (Aqua-Fit)
      for 45 min. Maternal heart rate was monitored continuously throughout the
      session. Blood pressure was measured before and after the session. RESULTS: Mean
      left leg volume decreased by 112 ml from 1665 to 1553 ml, and right leg volume by
      84 ml from 1665 to 1581 ml (P = 0.007). Cardiovascular parameters fluctuated
      within the normal range, well below the upper limits recommended in pregnancy.
      CONCLUSIONS: A single immersion exercise session is a safe, effective, and
      enjoyable complement, or alternative, to compression stockings for reduction of
      gestational dependent edema. Further study is required to determine its duration
      of effect and the optimum interval between sessions.

PMID- 16305700
TI  - Routine ultrasound screening in the third trimester: a population-based study.
AB  - BACKGROUND: No population-based study has evaluated the effects of third
      trimester ultrasound screening on prognosis. OBJECTIVE: To study the effects of
      routine ultrasound screening in the third trimester on perinatal/infant
      mortality, prevalence of small for gestational age infants (SGA) and low Apgar
      score. STUDY DESIGN: Two university clinics using routine ultrasound screening in
      the third trimester were compared with seven county or district hospitals with no
      routine screening. Deliveries between 1985 and 1996 were included. In all, 16
      municipalities including 56 371 pregnancies with routine screening were compared
      with 59 municipalities and 153 355 pregnancies without third trimester screening.
      An observational design was applied, using data stored during pregnancy,
      delivery, and during the first year (infant mortality) at the Swedish Medical
      Birth Registry, The National Board of Health and Welfare. Odds ratio with 95%
      confidence interval was used in the evaluation. End-points included incidence of
      SGA, perinatal/infant mortality, Apgar score at 5 min, cesarean section and
      instrumental delivery in areas with versus without routine third trimester
      screening. RESULTS: No significant difference was seen in the prevalence of the
      most extreme SGA (< -3 SD from the mean), perinatal complications including
      cesarean section or instrumental delivery, or perinatal/infant mortality between
      units with versus without routine ultrasound screening in the third trimester.
      CONCLUSION: Added to the findings of previous small randomized studies, it seems
      as if routine third trimester ultrasound screening in an unselected population
      does not reduce perinatal mortality or early neonatal morbidity, expressed as
      Apgar scores or SGA.

PMID- 16305701
TI  - Gestational diabetes: a reappraisal of HBA1c as a screening test.
AB  - BACKGROUND: Recent technological advances have made HBA1c a more standardized and
      user-friendly test with wide availability. This study evaluated HBA1c as a
      screening test for gestational diabetes mellitus (GDM) in a high-risk population.
      METHODS: A total of 442 pregnant women were assessed by HBA1c. Two thresholds
      were used to "rule in or rule out" GDM, which was confirmed by the "gold
      standard" 75-g OGTT (World Health Organization criteria). RESULTS: Eighty-four
      (19%) women had GDM while 358 (81%) women were normal; there was a complete
      overlap of the HBA1c histograms of the two populations. The area under receiver
      operating characteristic curve of HBA1c to detect GDM was 0.54 (95% CI 0.48
      0.61). Using a value of <5.5% to rule out GDM; a sensitivity of 82.1% was
      achieved, with 15 (16.7%) of 90 women below the threshold being false-negatives
      (NPV = 83.3%). Using a threshold of HBA1c > or = 7.5% to rule-in GDM; the
      specificity was 95.8% with 15 (71.4%) of 21 patients over the threshold being
      false-positives (PPV = 28.6%). HBA1c would eliminate the need for an OGTT in
      25.1% (111/442) of whom 27% (30/111) women would be misclassified. At any HBA1c
      threshold with an acceptable sensitivity, the false-positive rate remained high
      making it necessary for too many healthy women to undergo the confirmatory OGTT.
      CONCLUSION: Despite all the progress in methodology, HBA1c remains a poor test to
      screen for GDM.

PMID- 16305702
TI  - Sympathetic responsibility in ethically difficult situations.
AB  - BACKGROUND: Ethical issues arise in many obstetric situations and demand constant
      consideration by obstetricians. The aim of this study was to highlight the
      meaning of being in an ethically difficult situation as narrated by
      obstetricians. METHODS: A descriptive design with a qualitative approach using a
      hermeneutic phenomenological method for analysis. Interviews were performed with
      14 obstetricians working in a Swedish hospital setting. RESULTS: The overriding
      theme was Sympathetic responsibility in the decisions of critical importance for
      the mother and her infant. Five related themes were to: (i) proceed with a moral
      reasoning that leads to the choice of a possible solution; (ii) balance one's own
      medical knowledge and moral insight with the needs and requests of the parents;
      (iii) be aware of one's medical and moral responsibility in relation to the
      decision made; (iv) experience the ability to take action and to make and carry
      out difficult and important decisions relating to the health of the mother and
      infant; and (v) reflect on a given situation in a manner leading to a rational
      acceptance of one's own conduct. CONCLUSIONS: Sympathetic responsibility is the
      structure of the meaning of the obstetricians' lived experience, which means that
      the obstetricians with the help of their medical knowledge and their desire to
      support the mother's autonomy do what is best for the mother and her infant.
      Implications include that an exchange of ethical thoughts and moral reasoning
      should lead to a higher degree of mutual understanding between colleagues and
      between the different professionals. Co-operation is important to achieve the
      best outcome for the mother and her infant.

PMID- 16305703
TI  - Ruptured uterus in a Nigerian community: a study of sociodemographic and
      obstetric risk factors.
AB  - BACKGROUND: Ruptured uterus is a common obstetric emergency in Nigeria,
      associated with high maternal and perinatal morbidity and mortality. There is a
      need for definitive identification of the risk factors to guide effective
      interventions to curb its scourge. OBJECTIVE: To identify the sociodemographic
      and obstetric risk factors for ruptured uterus in Benin City, Nigeria, and based
      on this, make appropriate recommendations toward curbing the incidence and
      morbidity and mortality associated with it. MATERIALS AND METHODS:
      Sociodemographic and obstetric variables in 51 women with ruptured uterus and 300
      randomly selected hospital controls from the general obstetric population were
      compared. Fisher's exact test was used to determine statistical significance
      between proportions. RESULTS: The incidence of ruptured uterus was 1 in 426
      deliveries. The risk factors found were low socioeconomic class (OR = 6.8, CI =
      3.6-12.9), being unbooked for antenatal care (OR = 10.4, CI = 5.4-20.0), grand
      multiparity (OR = 8.7, CI = 4.0-19.1), and prolonged obstructed labor (OR = 35.3,
      CI = 15.3-81.6). CONCLUSION: Measures that promote education and economic
      empowerment of women and the utilization of modern antenatal care will reduce the
      prevalence of rupture of the uterus in the community.

PMID- 16305704
TI  - Beat-to-beat estimate of fetal cardiac time intervals using magnetocardiography:
      longitudinal charts of normality ranges and individual trends.
AB  - BACKGROUND: Fetal magnetocardiography (fMCG) records fetal cardiac electro
      physiological activity during the second half of gestation. We aimed at assessing
      normality values, related variability, and trends of fetal cardiac time intervals
      (fCTI) evaluated longitudinally from beat-to-beat fMCG analysis in uncomplicated
      pregnancies. MATERIALS AND METHODS: The fMCG were recorded with multi-channel
      system in shielded room. FCTI were estimated on more than 2600 fetal cardiac
      cycles from 51 fMCG data sets of uncomplicated pregnancies. Independent component
      analysis (ICA) allowed reconstructing reliable fetal signals for beat-to-beat
      identification of fCTI (RR, P wave, PQ, PR, QT, QTc, QRS, ST, and T wave); intra
      individual variability analysis and trends were calculated; reference
      longitudinal charts accounted for intra- and inter-individual variations and were
      compared with figures estimated on averaged signals. RESULTS: For each data set,
      fCTI were calculated beat-to-beat on rhythm strips of more than 50 beats (95%
      overall detection rate). FCTI values, variability, and trends were in good
      agreement with available reference figures; intervals related to P and T waves
      were, respectively, underestimated and overestimated with respect to those
      estimated on averaged signals or obtained by other research groups. Errors were
      reduced and individual trends could be drawn. CONCLUSIONS: ICA permitted the
      reconstruction of reliable time course of fetal cardiac signals and the beat-to
      beat calculation of time intervals, and normality ranges, with smaller errors
      with respect to previous studies. The retrieval of fetal traces with clear
      morphology and the longitudinal character of the study allowed estimating
      individual trends and beat-to-beat characterization, impossible with cross
      sectional studies on averaged beats.

PMID- 16305705
TI  - The impact of oxygen tension on developmental competence of post-thaw human
      embryos.
AB  - The present study compares the culture of human embryos using two different
      culture systems: a conventional culture incubator with humidified atmospheric air
      supplemented with 5% CO(2) and a closed culture incubator with a humidified 5%
      O(2) and 5% (5.2-5.5) CO(2) and 90% N(2) partial pressure. A total of 225
      cryopreserved embryos were donated after informed consent and thawed in two
      batches of 100 and 125 embryos separated by 1 week. A total of 126 (56%) embryos
      survived the thawing procedure having at least one living blastomere. After
      thawing, the embryos were randomly allocated to culture in a 5% oxygen partial
      pressure (n = 65) or to culture in a 20% oxygen partial pressure (n = 61). The
      embryos were hereafter cultured for 4 days and the number of embryos developed to
      morula stage or blastocyst stage was examined. The results of the embryo culture
      in the two trials performed showed an increase from 43% to 68% (19 to 68%) morula
      formation in trial 1 (trial 2), i.e. on the whole the morula yield more than
      doubled in favor of culture in a 5% oxygen partial pressure compared with a 20%
      oxygen partial pressure.

PMID- 16305706
TI  - In vitro fertilization in Sweden: maternal characteristics.
AB  - BACKGROUND: Deliveries among women who had an in vitro fertilization (IVF) are
      characterized by increased risks for both the mother and the infant/child. Part
      of these effects may be due to maternal characteristics. METHODS: Using reports
      from all clinics performing IVF in Sweden, 12 186 women who gave birth after such
      procedures were identified (13 261 deliveries, 16 280 infants born). Various
      social and medical characteristics of the women were studied and compared with
      all women giving birth. Information was retrieved by interviews in early
      pregnancy or by linkage with various registers. RESULTS: Women who had IVF were
      older than other women who gave birth and were older after standard IVF than
      after intracytoplasmatic sperm injection (ICSI). They were more often of first
      parity and smoked less than other delivered women. There were more women with
      high body mass index: they worked outside home less often and were more often of
      Swedish nationality. Women who had standard IVF had more previous miscarriages
      than expected, but this was not true for women who had ICSI. Their pattern of
      drug usage differed from that of other women who had given birth. CONCLUSIONS:
      Women who underwent IVF and gave birth showed marked deviations from other women
      who gave birth. Some of these characteristics may help to explain the increased
      risks associated with these procedures. Women who had ICSI were less deviating
      than women who had standard IVF.

PMID- 16305707
TI  - Risk factors for glucose intolerance in Danish women with polycystic ovary
      syndrome.
AB  - BACKGROUND: Women with polycystic ovary syndrome (PCOS) are reported to be at
      risk for glucose intolerance. The aim of the study was to describe these risk
      factors in a population of Danish PCOS women attending a gynecologic clinic and
      to identify the parameters with the strongest correlation to the fasting blood
      glucose levels. In addition, we studied whether the oral glucose tolerance test
      (OGTT) diagnosed more cases of glucose intolerance in this PCOS population than
      the fasting plasma glucose value (FPG) alone. METHODS: Cross-sectional study of
      91 women with oligomenorrhea or amenorrhea and elevated serum testosterone,
      followed by an OGTT in 27 of the women. RESULTS: Women with a FPG above normal
      were older and had a higher body mass index (BMI), cholesterol, and triglycerides
      and a lower sexual hormone binding globulin (SHBG). Of the 21 women older than
      34, eight (38%) had a FPG above normal. The OGTT study showed that one of five
      with abnormal glucose tolerance would not have been diagnosed, if the FPG alone
      had been performed. CONCLUSIONS: In this study, 38% of women with symptoms of
      PCOS over the age of 34 had abnormal blood glucose values. These women should
      receive blood glucose testing regardless of BMI, testosterone levels and family
      history of type 2 diabetes mellitus. An OGTT may be necessary to find all cases
      of impaired glucose intolerance.

PMID- 16305708
TI  - Maternal underweight and the risk of spontaneous abortion.
AB  - BACKGROUND: To evaluate the risk of spontaneous abortion in relation to maternal
      pre-pregnant underweight. METHODS: The study was designed as a cohort study
      within the framework of the Danish National Birth Cohort (DNBC). The participants
      were a total of 23 821 women recruited consecutively to the DNBC from October 1,
      1997 to March 31, 1999 and interviewed subsequently. The pregnant women were
      recruited in first half of pregnancy and interviewed about pre-pregnant body
      size, obstetric history, exposures in pregnancy, and socio-demographic factors.
      Pregnancies were followed-up regarding spontaneous abortion. Relative risk of
      spontaneous abortion was calculated as Hazard Ratios using Cox regression with
      delayed entry. RESULTS: The outcome measure was spontaneous abortion. The hazard
      ratio for spontaneous abortion in women with a pre-pregnant body mass index (BMI)
      below 18.5 was 1.24 (95% confidence limits 0.95-1.63) compared to women with pre
      pregnant BMI 18.5-24.9. Women with a BMI of 25 or more had a smaller increase in
      risk of spontaneous abortion. Adjustment for maternal age, parity, previous
      miscarriages, and lifestyle factors did not affect the estimates substantially,
      neither did exclusion of women with metabolic or eating disorders. CONCLUSION:
      These results indicate that pre-pregnant underweight may affect the risk of
      spontaneous abortion negatively.

PMID- 16305709
TI  - "Older" age is a risk factor for pelvic inflammatory disease in intrauterine
      device users.
AB  - BACKGROUND: To asses the role of a copper intrauterine device (IUD) per se in the
      development of pelvic inflammatory disease (PID) and complicated PID in women
      considered at low risk of PID. METHODS: Cases were 51 women admitted to hospital
      with a diagnosis of acute PID, and controls were 50 healthy women attending an
      outpatient clinic for routine gynecological check-up. The women were 25-45 years
      old. Data were analyzed and compared between groups using the statistical program
      package sas. RESULTS: IUD use was not associated with an increased risk of PID in
      general, but in women > or =35 years, IUD use was associated with a risk of PID
      [odds ratio (OR) = 4.2, confidence interval (CI) 1.1-16.3]. When adjusting for
      smoking, educational level, employment, and microbial findings in women with PID,
      IUD use was associated with complicated PID in women > or =35 years (OR = 33.9,
      CI 1.2-959.6), but not in younger women. When adjusting age and IUD use duration
      for each other in IUD users, age > or =35 years was a significant risk factor for
      PID (OR = 4.9, CI 1.3-19.2), but not long (> or =5 years) duration. In IUD users
      with PID, age > or =35 years was a risk factor for a PID to be complicated in
      both the unadjusted and adjusted analysis (OR = 12.7, CI 1.6-102.3; OR = 12.1, CI
      1.4-104.7), whereas long duration of IUD use was not. When adjusting for
      significant endocervical microbial findings, long duration of IUD use and age,
      only age > or =35 years, remained significantly associated with both PID and
      complicated PID (OR = 5, CI 1.1-21.9; OR = 36, CI - 1.9-670). CONCLUSIONS: IUD
      use was not associated with PID in low-risk younger women, but in women > or =35
      years, IUD use was associated with an increased risk of PID. The study also
      demonstrates an association between IUD use and complicated PID in women > or =35
      years.

PMID- 16305710
TI  - Spontaneous hemoperitoneum from a uterine leiomyoma in pregnancy.

PMID- 16305711
TI  - Failure to perform intrapartum electronic fetal monitoring due to ichthyosis, a
      fetal skin disease.

PMID- 16305712
TI  - Repair of vesico-uterine fistula with the O'Conor technique.

PMID- 16305713
TI  - Postnatal Group A Streptococcal infection in the upper genital tract.

PMID- 16305714
TI  - Successful preconceptional prophylactic treatment with combined acetyl salicylic
      acid and low-molecular heparin (Fragmin) in a case of antiphospholipid-antibody
      syndrome with prior life-threatening hemolysis, elevated liver enzymes and low
      platelet syndrome: a case report.

PMID- 16305718
TI  - Review article: The role of serotonergic agents in the treatment of patients with
      primary chronic constipation.
AB  - Chronic constipation is a highly prevalent disorder that is associated with
      significant direct and indirect costs and has substantial impact on patient
      quality of life. It is more common among women and non-white populations and is
      evenly distributed across adult age groups. Constipation is a heterogeneous
      disorder associated with multiple symptoms and aetiologies. Recent research has
      increased our understanding of the pathogenesis of this disorder and the central
      role of the neurotransmitter serotonin in mediating gastrointestinal motility,
      secretion and sensation. Abnormal serotonin signalling and reuptake appear to
      play central roles in the symptoms of a subset of patients with chronic
      constipation. This observation provides a rationale for the use of targeted
      serotonergic agents for the treatment of chronic constipation. As the role of
      serotonin in gastrointestinal function is further elucidated and additional
      candidate drugs are developed, it is likely that serotonergic agents will afford
      additional treatment options for patients with chronic constipation. This article
      provides a concise review of the evidence supporting a role for serotonin in the
      pathogenesis of chronic constipation and a summary of the currently available
      evidence supporting the use of serotonergic agents for this disorder.

PMID- 16305719
TI  - Review article: The history of hypnotherapy and its role in the irritable bowel
      syndrome.
AB  - Hypnosis is a technique by which an individual can gain a degree of control over
      physiological as well as psychological function. This paper reviews the history
      of the phenomenon as well as the accumulating evidence that it is effective in
      relieving the symptoms of irritable bowel syndrome and improving the quality of
      life of sufferers. The physiological effects of hypnosis are also discussed
      coupled with an outline of how a hypnotherapy service might be provided.

PMID- 16305720
TI  - Review article: Population screening for colorectal cancer.
AB  - Colorectal cancer is a common cancer and common cause of death. The mortality
      rate from colorectal cancer can be reduced by identification and removal of
      cancer precursors, adenomas, or by detection of cancer at an earlier stage. Pilot
      screening programmes have demonstrated decreased colorectal cancer mortality; as
      a result many countries are developing colorectal cancer screening programmes.
      The most common modalities being evaluated are faecal occult blood testing,
      flexible sigmoidoscopy and colonoscopy. Implementation of screening tests has
      been hampered by cost, invasiveness, availability of resources and patient
      acceptance. New technologies such at computed tomographic colonography and stool
      screening for molecular markers of neoplasia are in development as potential
      minimally invasive tools. This review considers who should be screened, which
      test to use and how often to screen.

PMID- 16305721
TI  - Systematic review: The model for end-stage liver disease--should it replace Child
      Pugh's classification for assessing prognosis in cirrhosis?
AB  - BACKGROUND: Prognosis in cirrhotic patients has had a resurgence of interest
      because of liver transplantation and new therapies for complications of end-stage
      cirrhosis. The model for end-stage liver disease score is now used for allocation
      in liver transplantation waiting lists, replacing Child-Turcotte-Pugh score.
      However, there is debate as whether it is better in other settings of cirrhosis.
      AIM: To review studies comparing the accuracy of model for end-stage liver
      disease score vs. Child-Turcotte-Pugh score in non-transplant settings. RESULTS:
      Transjugular intrahepatic portosystemic shunt studies (with 1360 cirrhotics) only
      one of five, showed model for end-stage liver disease to be superior to Child
      Turcotte-Pugh to predict 3-month mortality, but not for 12-month mortality.
      Prognosis of cirrhosis studies (with 2569 patients) none of four showed
      significant differences between the two scores for either short- or long-term
      prognosis whereas no differences for variceal bleeding studies (with 411
      cirrhotics). Modified Child-Turcotte-Pugh score, by adding creatinine, performed
      similarly to model for end-stage liver disease score. Hepatic encephalopathy and
      hyponatraemia (as an index of ascites), both components of Child-Turcotte-Pugh
      score, add to the prognostic performance of model for end-stage liver disease
      score. CONCLUSIONS: Based on current literature, model for end-stage liver
      disease score does not perform better than Child-Turcotte-Pugh score in non
      transplant settings. Modified Child-Turcotte-Pugh and model for end-stage liver
      disease scores need further evaluation.

PMID- 16305722
TI  - Personal view: Why is my GI clinic filled with surgical mishaps? Post-operative
      syndromes as an externality problem.
AB  - The aim of the present analysis was to review why gastroenterology clinics appear
      filled with patients suffering from postsurgical syndromes. The long-term
      sequelae of gastrointestinal surgery can be modelled as a negative production
      externality of surgical operations. When seeking to maximize their profits,
      surgeons are primarily concerned with the price and cost of surgery alone. They
      tend to ignore parts of the ensuing long-term costs they impose through
      postsurgical syndromes on other medical specialties. The complication-related
      rise in the cost of gastroenterology practice reflects parts of the societal
      costs of surgery that are not included on the surgical balance sheet. To the
      surgeon, surgery appears cheaper than to the rest of the medical community,
      because cost shifting from surgery to other medical specialties leads to a
      favourable surgical outcome with more surgical operations performed than
      medically needed or economically feasible. The amount of surgical sequelae could
      drop, if surgeons were forced to care for all their own postsurgical syndromes or
      if surgery entered a joint enterprise with gastroenterology caring for the same
      patient pool.

PMID- 16305723
TI  - Efficacy and tolerability of oral iron therapy in inflammatory bowel disease: a
      prospective, comparative trial.
AB  - BACKGROUND: In patients with inflammatory bowel disease, oral iron is anecdotally
      reported to be less effective and less well tolerated than in those without
      inflammatory bowel disease, and to increase disease activity. AIM: To study
      prospectively the effects of oral iron in patients with and without inflammatory
      bowel disease. METHODS: Patients with ulcerative colitis, Crohn's disease and non
      inflammatory bowel disease controls, all with iron deficiency anaemia, were
      assessed with symptom diaries, a quality of life questionnaire (Inflammatory
      Bowel Disease Questionnaire; inflammatory bowel disease patients only) and blood
      tests to measure iron repletion, disease activity and antioxidant capacity before
      and after starting 4 weeks of oral iron. In patients with ulcerative colitis,
      sigmoidoscopic scoring and rectal biopsies for reactive oxygen metabolite
      production were performed before and after iron therapy. RESULTS: All groups
      showed increases in haemoglobin and ferritin. Iron intolerance occurred in about
      a quarter of patients in each group. Two of 33 (6%) of inflammatory bowel disease
      patients had a relapse during treatment. Symptoms worsened in ulcerative colitis,
      but not in Crohn's disease or non-inflammatory bowel disease patients;
      Inflammatory Bowel Disease Questionnaire scores improved in ulcerative colitis.
      Laboratory markers of disease activity, sigmoidoscopic scores, histological
      scores, antioxidant capacity levels and reactive oxygen metabolite production did
      not change. CONCLUSIONS: Oral iron is equally efficacious and well tolerated in
      inflammatory bowel disease and non-inflammatory bowel disease patients. A tiny
      minority of inflammatory bowel disease patients relapse in association with use
      of oral iron therapy.

PMID- 16305724
TI  - Clinical evolution of luminal and perianal Crohn's disease after inducing
      remission with infliximab: how long should patients be treated?
AB  - BACKGROUND: Few data are available regarding the evolution of Crohn's disease
      after discontinuing a successful course of infliximab. AIM: To evaluate clinical
      outcome of Crohn's disease after induction of remission with three infliximab
      infusions (luminal disease) and after maintenance of remission with 1-year course
      of infliximab every 8 weeks (luminal and perianal). METHODS: Twenty-three
      patients with active luminal Crohn's disease who responded to three infusions of
      infliximab (0, 2, and 6 weeks), and 23 patients with sustained response to
      infliximab every 8 weeks during 1 year, were included. Patients were followed-up
      until relapse or for at least 6 months after infliximab discontinuation. Clinical
      outcomes and factors associated to relapse were evaluated. RESULTS: In luminal
      Crohn's disease, a three-infusion infliximab regimen achieved a sustained
      response in most patients, especially if a complete response occurred at the time
      of the third infusion. In patients treated for 1-year, infliximab discontinuation
      was also successful, with a cumulative probability of being free of relapse of
      69% at 12 months. In perianal disease, early relapse was the rule after stopping
      infliximab treatment, with only 34% of patient maintaining remission at 1 year.
      CONCLUSIONS: Short regimens of infliximab might be evaluated in patients with
      luminal Crohn's disease. However, infliximab discontinuation is not recommended
      in perianal Crohn's disease, because of a high rate of early relapse.

PMID- 16305725
TI  - Long-term follow-up of collagenous colitis after induction of clinical remission
      with budesonide.
AB  - BACKGROUND: Budesonide (Entocort) is effective for the treatment of collagenous
      colitis. AIM: To assess the long-term outcome of patients after induction of
      clinical remission by budesonide treatment. METHODS: Fifty-one patients with
      chronic diarrhoea and histologically proven collagenous colitis were enrolled in
      randomized, placebo-controlled crossover trial using budesonide 9 mg daily for 6
      weeks. Patients in clinical remission after either initial or crossover
      budesonide treatment were followed using standardized questionnaires. Clinical
      relapse was defined as five or more loose stools/day for at least 4 consecutive
      days. RESULTS: A total of 33 patients achieved clinical remission (85% per
      protocol). During a median follow-up of 16 months, clinical relapse occurred in
      20 patients (61%), after a median time of 2 weeks (range: 1-104, mean: 10 weeks).
      Patient age <60 years was identified as a significant risk factor for clinical
      relapse (OR = 7.4, P = 0.048). Budesonide was used for treatment of clinical
      relapse in 80% of patients achieving clinical response in all of them.
      CONCLUSIONS: Budesonide is effective in the treatment of collagenous colitis.
      Clinical relapses may occur in a considerable number of patients, particularly in
      those <60 years. Treatment of clinical relapse with budesonide appears to be an
      effective option.

PMID- 16305726
TI  - Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients
      with active Crohn's disease compared with omega-6 fatty acids.
AB  - BACKGROUND: Crohn's disease is a chronic inflammatory condition affecting the
      gastrointestinal tract. Polyunsaturated omega-3 fatty acids given orally may
      reduce the secretion of proinflammatory cytokines and hereby downregulate the
      inflammatory process. AIM: To assess the effects of enteral fatty acids, in the
      form of Impact Powder (Novartis, Switzerland), as adjuvant therapy to
      corticosteroid treatment on the proinflammatory and anti-inflammatory cytokine
      profiles in patients with active Crohn's disease. METHODS: The proinflammatory
      and anti-inflammatory cytokines were measured in plasma from 31 patients with
      active Crohn's disease. Patients were randomized for oral intake of omega-3 fatty
      acid (3-Impact Powder) or omega-6 fatty acids (6-Impact Powder). Clinical and
      biochemical markers of inflammation were studied at baseline and after 5 and 9
      weeks. RESULTS: Within the 3-Impact Powder group, no significant changes in
      concentrations of interleukin-6, interferon-gamma, monocyte chemoattractant
      protein-1, interleukin-2, interleukin-5 and interleukin-10, whereas a significant
      differences in concentration of interleukin-1beta and interleukin-4 were observed
      during therapy. Within the 6-Impact Powder group a significant changes in
      concentrations of interleukin-1beta, interleukin-6, interferon-gamma, monocyte
      chemoattractant protein-1, interleukin-2, interleukin-4, interleukin-5 and
      interleukin-10 were observed. CONCLUSIONS: The 3-Impact Powder showed
      immunomodulatory properties and might inhibit an increase of proinflammatory
      cytokines in contrast to the 6-Impact Powder.

PMID- 16305727
TI  - Multidrug resistance 1 gene polymorphisms are not associated with inflammatory
      bowel disease and response to therapy in Italian patients.
AB  - BACKGROUND: Host genetic factors may be important in determining not only disease
      susceptibility, but also disease behaviour and response to therapy in
      inflammatory bowel disease. Two polymorphisms (C3435T and G2677T/A) of the
      multidrug resistance 1 gene have been correlated with the altered P-glycoprotein
      expression and function in humans, and associated with predisposition to
      ulcerative colitis and Crohn's disease. AIM: To investigate the contribution of
      these polymorphisms to disease susceptibility and response to medical therapy.
      METHODS: A total of 946 inflammatory bowel disease patients (478 Crohn's disease,
      272 males, mean age 43 +/- 14 years and 468 ulcerative colitis, 290 males, mean
      age 48 +/- 15 years) and 450 healthy controls were genotyped for the single
      nucleotide polymorphisms C3435T and G2677T/A. Patients were also classified on
      the basis of response to medical therapy (mesalazine, steroids,
      immunosuppressives and infliximab). RESULTS: Both single nucleotide polymorphisms
      were in Hardy-Weinberg equilibrium and significant linkage disequilibrium. No
      significant difference in the allele, genotype, and haplotype frequencies was
      found in both Crohn's disease and ulcerative colitis patients compared with the
      controls. No correlation with clinical features was found, except for a reduced
      frequency of extra-intestinal manifestations in Crohn's disease patients with the
      G2677T genotype (40%) compared with GG2677 and 2677TT genotypes (54% and 58%,
      respectively) (P = <0.02). No significant difference was also found after
      stratifying the patients on the basis of their response to medical therapy.
      CONCLUSION: The investigated polymorphisms of the multidrug resistance 1 gene
      have no significant role in disease susceptibility and response to medical
      therapy in our Italian population of inflammatory bowel disease patients.

PMID- 16305728
TI  - Diagnostic accuracy of the serum profile of gastric mucosa in relation to
      histological and morphometric diagnosis of atrophy.
AB  - BACKGROUND: Histology is the gold standard for diagnosis of atrophy but is
      hampered by observer variation. A reliable method to overcome this issue is
      morphometric analysis of gastric mucosa. Serum pepsinogens and gastrin have been
      proposed in the diagnostic work-up of gastric atrophy although diagnostic
      accuracy of these tests is considered unsatisfactory. AIM: To evaluate the
      diagnostic accuracy of gastric serum profile in relation both to morphological
      and morphometric diagnosis of gastric atrophy. METHODS: Ninety-four dyspeptic out
      patients underwent upper endoscopy and evaluation of serum levels of PGI, PGII
      and 17-gastrin. Diagnostic accuracy of gastric serum profile was tested by
      receiver operating characteristic curves and by evaluation of sensitivity and
      specificity in relation to both histology and morphometric analyses. RESULTS: As
      far as concern to histological evaluation, only PGI/PGII ratio showed an
      acceptable diagnostic accuracy in discrimination of gastric atrophy, while, when
      morphometric analysis was considered as reference, both serum PGI level and
      PGI/PGII ratio showed an excellent performance. However, both PGI and PGI/PGII
      ratio showed low sensitivity and high specificity. CONCLUSIONS: Serological
      gastric profile corresponds better with the morphometric diagnosis of atrophy,
      even if, because of the low sensitivity, today this could only be used as
      screening test of chronic atrophic gastritis.

PMID- 16305729
TI  - Comprehension and awareness of symptoms in women with dyspepsia.
AB  - BACKGROUND: Overlapping symptoms of gastro-oesophageal reflux disease and
      dyspepsia are a problem for physicians and patients. AIM: This study explored
      comprehension of dyspepsia symptoms and associated medical terminology among
      women with symptoms of dyspepsia. METHODS: The US women aged > or = 18 years with
      dyspepsia (defined by Rome II criteria) were recruited in two phases, via direct
      mail, the Internet, clinical investigators and/or gastroenterologists. In phase
      I, subjects took part in an hour-long telephonic interview comprising open-ended
      questions relating to symptom frequency/duration, triggers/patterns and severity.
      During phase II, subjects took part in a 45-min telephonic interview, which
      explored their understanding of dyspepsia symptoms and their predominant or most
      bothersome symptom. RESULTS: Subjects with 'pure' dyspepsia (without overlapping
      symptoms of gastro-oesophageal reflux disease or irritable bowel syndrome) were
      sought, but of 777 subjects screened, most were excluded because of
      gastrointestinal comorbidities (irritable bowel syndrome, gastro-oesophageal
      reflux disease). Only 85 (11%) subjects had 'pure' dyspepsia of whom 11 withdrew.
      Of the 74 subjects interviewed, 70% were unfamiliar with the term 'dyspepsia'.
      Subjects reported several symptoms, including bloating (65%), gas (50%), nausea
      (41%) and discomfort (36%). Most subjects could distinguish between symptom
      bothersomeness and severity, and between pain and discomfort. Terms such as
      'satisfactory relief', 'central upper abdominal discomfort', 'early satiety' and
      'postmeal fullness' were often misunderstood. CONCLUSIONS: Subjects with 'pure'
      dyspepsia are rare, because of comorbidities. Dyspepsia-related terminology is
      often misunderstood by subjects.

PMID- 16305730
TI  - Hydrogen glucose breath test to detect small intestinal bacterial overgrowth: a
      prevalence case-control study in irritable bowel syndrome.
AB  - BACKGROUND: Studies assessing the prevalence of small intestinal bacterial
      overgrowth in irritable bowel syndrome gave contrasting results. Differences in
      criteria to define irritable bowel syndrome patients and methods to assess small
      intestinal bacterial overgrowth may explain different results. Moreover, no data
      exist on small intestinal bacterial overgrowth prevalence in a significant
      population of healthy non-irritable bowel syndrome subjects. AIM: To assess the
      prevalence of small intestinal bacterial overgrowth by glucose breath test in
      patients with irritable bowel syndrome symptoms with respect to a consistent
      control group. METHODS: Consecutive patients with irritable bowel syndrome
      according to Rome II criteria were enrolled. The control population consisted of
      102 sex- and age-matched healthy subjects without irritable bowel syndrome
      symptoms. All subjects underwent glucose breath test. A peak of H2 values >10
      p.p.m above the basal value after 50 g of glucose ingestion was considered
      suggestive of small intestinal bacterial overgrowth. RESULTS: A total of 65
      irritable bowel syndrome patients and 102 healthy controls were enrolled.
      Positivity to glucose breath test was found in 31% of irritable bowel syndrome
      patients with respect to 4% in the control group, the difference between groups
      resulting statistically significant (OR: 2.65; 95% CI: 3.5-33.7, P < 0.00001).
      CONCLUSIONS: The present case-control study showed an epidemiological association
      between irritable bowel syndrome and small intestinal bacterial overgrowth.
      Placebo-controlled small intestinal bacterial overgrowth-eradication studies are
      necessary to clarify the real impact of small intestinal bacterial overgrowth on
      irritable bowel syndrome symptoms.

PMID- 16305731
TI  - Observations on the use of allopurinol in combination with azathioprine or
      mercaptopurine.

PMID- 16305732
TI  - Global endpoints in functional gastrointestinal disease.

PMID- 16305734
TI  - Management of rectal cancer--is adjuvant radiotherapy safe for the elderly?

PMID- 16305735
TI  - Colonoscopy should intubate the terminal ileum.

PMID- 16305737
TI  - IMGT, the international ImMunoGeneTics information system: a standardized
      approach for immunogenetics and immunoinformatics.
AB  - IMGT, the international ImMunoGeneTics information system http://imgt.cines.fr,
      was created in 1989 by the Laboratoire d'ImmunoGenetique Moleculaire (LIGM)
      (Universite Montpellier II and CNRS) at Montpellier, France. IMGT is a high
      quality integrated knowledge resource specialized in immunoglobulins (IG), T cell
      receptors (TR), major histocompatibility complex (MHC) of human and other
      vertebrates, and related proteins of the immune system (RPI) of any species which
      belong to the immunoglobulin superfamily (IgSF) and to the MHC superfamily
      (MhcSF). IMGT consists of five databases, ten on-line tools and more than 8,000
      HTML pages of Web resources. IMGT provides a common access to standardized data
      from genome, genetics, proteome and three-dimensional structures. The accuracy
      and the consistency of IMGT data are based on IMGT-ONTOLOGY, a semantic
      specification of terms to be used in immunogenetics and immunoinformatics. IMGT
      ONTOLOGY comprises six main concepts: IDENTIFICATION, CLASSIFICATION,
      DESCRIPTION, NUMEROTATION, ORIENTATION and OBTENTION. Based on these concepts,
      the controlled vocabulary and the annotation rules necessary for the
      immunogenetics data identification, classification, description and numbering and
      for the management of IMGT knowledge are defined in the IMGT Scientific chart.
      IMGT is the international reference in immunogenetics and immunoinformatics for
      medical research (repertoire analysis of the IG antibody sites and of the TR
      recognition sites in autoimmune and infectious diseases, AIDS, leukemias,
      lymphomas, myelomas), veterinary research (IG and TR repertoires in farm and wild
      life species), genome diversity and genome evolution studies of the adaptive
      immune responses, biotechnology related to antibody engineering (single chain
      Fragment variable (scFv), phage displays, combinatorial libraries, chimeric,
      humanized and human antibodies), diagnostics (detection and follow up of residual
      diseases) and therapeutical approaches (grafts, immunotherapy, vaccinology). IMGT
      is freely available at http://imgt.cines.fr.

PMID- 16305738
TI  - Clinical and social outcomes five years after closing a mental hospital: a trial
      of cognitive behavioural interventions.
AB  - BACKGROUND: To investigate the outcome of patients transferred from hospital to
      community care in Como, Italy after 6 months intensive psychosocial
      rehabilitation prior to discharge. METHOD: All 149 residents with a primary
      psychiatric diagnosis were assigned to receive either a 6-month pre-discharge
      course of goal-oriented rehabilitation, (IT), or routine management, (RT). BPRS
      and GAF ratings were made by blind, independent assessors before and at 12, 24,
      36, 48, and 60 months after discharge and the results examined with repeated
      measures analysis of variance. RESULTS: Overall change in residence was achieved
      without any major detriment to the health and welfare of most patients. The
      cohort of patients who received intensive rehabilitation, (IT), prior to
      discharge showed significantly lower impairment and disability throughout the
      five years compared to the cohort receiving routine management, (RT), prior to
      discharge. Total BPRS scores remained significant when initial differences in the
      cohorts were covaried, whereas GAF failed to remain significant (p = 0.051).
      CONCLUSION: The treatment provided prior to transfer from long-stay hospital to
      community residence may have long-term clinical benefits for chronically disabled
      patients.

PMID- 16305739
TI  - Characterization of two candidate genes, NCoA3 and IRF8, potentially involved in
      the control of HIV-1 latency.
AB  - BACKGROUND: The persistence of latent HIV-1 reservoirs is the principal barrier
      preventing the eradication of HIV-1 infection in patients by current
      antiretroviral therapy. It is thus crucial to understand the molecular mechanisms
      involved in the establishment, maintenance and reactivation of HIV-1 latency.
      Since chromatin remodeling has been implicated in the transcriptional
      reactivation of the HIV-1 promoter, we assessed the role of the histone
      deacetylase inhibitor sodium butyrate (NaB) on two HIV-1 latently infected cell
      lines (U1 and ACH-2) gene expression. RESULTS: Analysis of microarrays data led
      us to select two candidate genes: NCoA3 (Nuclear Receptor Coactivator 3), a
      nuclear receptor coactivator and IRF8 (Interferon Regulatory Factor 8), an
      interferon regulatory factor. NCoA3 gene expression is upregulated following NaB
      treatment of latently infected cells whereas IRF8 gene expression is strongly
      downregulated in the promonocytic cell line following NaB treatment. Their
      differential expressions were confirmed at the transcriptional and translational
      levels. Moreover, NCoA3 gene expression was also upregulated after treatment of
      U1 and ACH-2 cells with phorbol myristyl acetate (PMA) but not trichostatin A
      (TSA) and after treatment with NaB of two others HIV-1 latently infected cell
      lines (OM10.1 and J1.1). IRF8 gene is only expressed in U1 cells and was also
      downregulated after treatment with PMA or TSA. Functional analyses confirmed that
      NCoA3 synergizes with Tat to enhance HIV-1 promoter transcription and that IRF8
      represses the IRF1-mediated activation through the HIV-1 promoter Interferon
      stimulated response element (ISRE). CONCLUSION: These results led us to postulate
      that NCoA3 could be involved in the transcriptional reactivation of the HIV-1
      promoter from latency and that IRF8 may contribute to the maintenance of the
      latent state in the promonocytic cell line. Implication of these factors in the
      maintenance or reactivation of the viral latency may provide potential new
      targets to control HIV-1 replication in latent viral reservoirs.

PMID- 16305740
TI  - A truncated Kv1.1 protein in the brain of the megencephaly mouse: expression and
      interaction.
AB  - BACKGROUND: The megencephaly mouse, mceph/mceph, is epileptic and displays a
      dramatically increased brain volume and neuronal count. The responsible mutation
      was recently revealed to be an eleven base pair deletion, leading to a frame
      shift, in the gene encoding the potassium channel Kv1.1. The predicted MCEPH
      protein is truncated at amino acid 230 out of 495. Truncated proteins are usually
      not expressed since nonsense mRNAs are most often degraded. However, high Kv1.1
      mRNA levels in mceph/mceph brain indicated that it escaped this control
      mechanism. Therefore, we hypothesized that the truncated Kv1.1 would be expressed
      and dysregulate other Kv1 subunits in the mceph/mceph mice. RESULTS: We found
      that the MCEPH protein is expressed in the brain of mceph/mceph mice. MCEPH was
      found to lack mature (Golgi) glycosylation, but to be core glycosylated and
      trapped in the endoplasmic reticulum (ER). Interactions between MCEPH and other
      Kv1 subunits were studied in cell culture, Xenopus oocytes and the brain. MCEPH
      can form tetramers with Kv1.1 in cell culture and has a dominant negative effect
      on Kv1.2 and Kv1.3 currents in oocytes. However, it does not retain Kv1.2 in the
      ER of neurons. CONCLUSION: The megencephaly mice express a truncated Kv1.1 in the
      brain, and constitute a unique tool to study Kv1.1 trafficking relevant for
      understanding epilepsy, ataxia and pathologic brain overgrowth.

PMID- 16305741
TI  - Incorporation of branched-chain fatty acid into cellular lipids and caspase
      independent apoptosis in human breast cancer cell line, SKBR-3.
AB  - BACKGROUND: 13-Methyltetradecanoic acid (13-MTD), an iso-C15 branched- chain
      saturated fatty acid, has been shown to induce apoptotic cell death of numerous
      human cancer cells. However, the mechanism for the induction of apoptosis has not
      been fully understood. This study described the incorporation of 13-MTD into
      cellular lipid of SKBR-3 breast cancer cells and apoptosis related event to gain
      more insight into the mechanism action of this fatty acid. RESULTS: Treatment of
      SKBR-3 cells with 13-MTD lowered the cell viability and induced apoptosis.
      Proportion of 13-MTD in the glycerolipids increased to saturation level within 6
      hours. Triacylglycerol contained 13-MTD in higher concentration than phospholipid
      with positional preference to sn-2. 13-MTD caused no changes in the caspase
      activity and its gene expression. Furthermore, addition of caspase-inhibitor to
      culture medium did not prevent the cells from the cytotoxicity of 13-MTD. No
      increase in the cellular calcium level was also noted with 13-MTD treatment.
      However, 13-MTD disrupted the mitochondrial integrity in 4 hours, and increased
      the nuclear translocation of apoptosis inducing factor. CONCLUSION: These results
      showed that 13-MTD disrupted the mitochondrial integrity, and induced apoptosis
      via caspase-independent death pathway.

PMID- 16305742
TI  - Recent developments in targeting access to high cost medicines in Australia.
AB  - BACKGROUND: In Australia, the Pharmaceutical Benefits Scheme (PBS) has developed
      a set of arrangements to control access to high-cost medicines to ensure their
      use is cost-effective. These medicines include the tumour necrosis factor-alpha
      inhibitors (TNFIs) for the treatment of rheumatoid arthritis. The aim of this
      first phase of a qualitative study was to explore basic views on the restricted
      access to TNFIs in order to confirm where further investigation should take place
      in the next phase. METHODS: Semi-structured interviews were conducted in 2004
      with a member of the four relevant stakeholder groups. Participants were asked
      their opinions about features of the establishment, process and effects of the
      system of restricted access to TNFIs. Views on the collaboration between
      stakeholder groups in the decision-making process were also collected. RESULTS:
      The principle of 'controlled access' to TNFIs was supported in general. There
      were concerns regarding some of the specific eligibility criteria. Wider and more
      transparent stakeholder consultation was judged desirable. Some flexibility
      around prescribing of TNFIs by physicians, and regular review of the arrangements
      were proposed. These themes will inform the next phase of the study. CONCLUSION:
      This first phase highlighted a range of issues associated with the PBS
      arrangements restricting access to TNFIs. Timely review and report of issues and
      concerns associated with such policy developments that arose in practice are
      essential. There is a need for a more comprehensive exploration across a wide
      range of stakeholders with different perspectives that will in turn be helpful in
      guiding policy and practice around national arrangements to manage access to high
      cost medicines.

PMID- 16305743
TI  - Comparative assessment of three different indices of multimorbidity for studies
      on health-related quality of life.
AB  - BACKGROUND: Measures of multimorbidity are often applied to source data,
      populations or outcomes outside the scope of their original developmental work.
      As the development of a multimorbidity measure is influenced by the population
      and outcome used, these influences should be taken into account when selecting a
      multimorbidity index. The aim of this study was to compare the strength of the
      association of health-related quality of life (HRQOL) with three multimorbidity
      indices: the Cumulative Illness Rating Scale (CIRS), the Charlson index
      (Charlson) and the Functional Comorbidity Index (FCI). The first two indices were
      not developed in light of HRQOL. METHODS: We used data on chronic diseases and on
      the SF-36 questionnaire assessing HRQOL of 238 adult primary care patients who
      participated in a previous study. We extracted all the diagnoses for every
      patient from chart review to score the CIRS, the FCI and the Charlson. Data for
      potential confounders (age, sex, self-perceived economic status and self
      perceived social support) were also collected. We calculated the Pearson
      correlation coefficients (r) of the SF-36 scores with the three measures of
      multimorbidity, as well as the coefficient of determination, R2, while
      controlling for confounders. RESULTS: The r values for the CIRS (range: -0.55 to 
      0.18) were always higher than those for the FCI (-0.47 to -0.10) and Charlson (
      0.31 to -0.04) indices. The CIRS explained the highest percent of variation in
      all scores of the SF-36, except for the Mental Component Summary Score where the
      variation was not significant. Variations explained by the FCI were significant
      in all scores of SF-36 measuring physical health and in two scales evaluating
      mental health. Variations explained by the Charlson were significant in only
      three scores measuring physical health. CONCLUSION: The CIRS is a better choice
      as a measure of multimorbidity than the FCI and the Charlson when HRQOL is the
      outcome of interest. However, the FCI may provide a good option to evaluate the
      physical aspect of HRQOL for the ease in its administration and scoring. The
      Charlson index may not be recommended as a measure of multimorbidity in studies
      related to either physical or mental aspects of HRQOL.

PMID- 16305744
TI  - Substance P selectively decreases paired pulse depression in the rat hippocampal
      slice.
AB  - BACKGROUND: Although being widespread in the hippocampus, the role tachykinins
      play in synaptic transmission is unclear. The effect of substance P on field
      potentials evoked by stimulation of the Schaffer collateral-commissural fibres
      and recorded from the CA1 region of the rat hippocampal slice were studied.
      RESULTS: Perfusion of substance P (8 microM) had no effect on the fEPSP or
      population spike. Substance P did however cause a selective reduction in the
      paired pulse depression of population spikes evoked by paired stimulation at
      interpulse intervals of 20-80 msec. A comparison of the actions of other
      tachykinin receptor agonists gave an order of potency of substance P > [beta
      Ala8]-neurokinin A (4-10) > senktide. The effect of substance P was reduced by
      the neurokinin-1 receptor antagonist SR140333, but not by the neurokinin-2 or
      neurokinin-3 receptor antagonists, MDL 29,913 or [Trp7, beta-Ala8]-neurokinin A
      (4-10). CONCLUSION: The order of potency of the agonists, and the effects of the
      antagonists, both indicate that the effect of substance P on paired pulse
      depression is mediated by neurokinin-1 receptors.

PMID- 16305745
TI  - Discover protein sequence signatures from protein-protein interaction data.
AB  - BACKGROUND: The development of high-throughput technologies such as yeast two
      hybrid systems and mass spectrometry technologies has made it possible to
      generate large protein-protein interaction (PPI) datasets. Mining these datasets
      for underlying biological knowledge has, however, remained a challenge. RESULTS:
      A total of 3108 sequence signatures were found, each of which was shared by a set
      of guest proteins interacting with one of 944 host proteins in Saccharomyces
      cerevisiae genome. Approximately 94% of these sequence signatures matched entries
      in InterPro member databases. We identified 84 distinct sequence signatures from
      the remaining 172 unknown signatures. The signature sharing information was then
      applied in predicting sub-cellular localization of yeast proteins and the novel
      signatures were used in identifying possible interacting sites. CONCLUSION: We
      reported a method of PPI data mining that facilitated the discovery of novel
      sequence signatures using a large PPI dataset from S. cerevisiae genome as input.
      The fact that 94% of discovered signatures were known validated the ability of
      the approach to identify large numbers of signatures from PPI data. The
      significance of these discovered signatures was demonstrated by their application
      in predicting sub-cellular localizations and identifying potential interaction
      binding sites of yeast proteins.

PMID- 16305746
TI  - Influence of static lumbar flexion on the trunk muscles' response to sudden arm
      movements.
AB  - BACKGROUND: Viscoelastic creep of lumbar ligaments (prolonged forward bend) has
      been shown to negatively influence the spine's muscular reflexive behaviour and
      spinal stability. No studies to date have investigated the influence of spinal
      viscoelastic creep on the feedforward response of the trunk muscles to sudden arm
      raises. METHODS: Surface myoelectric activity was collected from the transversus
      abdominis/internal oblique, the lower erector spinae and the deltoid muscle
      during sudden ballistic arm raising before and after 10 minutes of prolonged
      forward bend in 11 healthy participants free of low back injury. The timing of
      trunk muscle activity relative to the deltoid muscle was calculated for 5 trials
      before and 5 trials after the creep procedure. RESULTS: Viscoelastic creep had no
      influence on the feedforward response of the trunk muscles during sudden arm
      raises. A feedforward response of the trunk muscles was not seen in every study
      participant and during every trial. CONCLUSION: Passive trunk muscle fatigue does
      not appear to influence the timing of the stabilizing role of the investigated
      trunk muscles to sudden arm flexion.

PMID- 16305747
TI  - Characterization of the interactions between the active site of a protein
      tyrosine kinase and a divalent metal activator.
AB  - BACKGROUND: Protein tyrosine kinases are important enzymes for cell signalling
      and key targets for anticancer drug discovery. The catalytic mechanisms of
      protein tyrosine kinase-catalysed phosphorylation are not fully understood.
      Protein tyrosine kinase Csk requires two Mg2+ cations for activity: one (M1)
      binds to ATP, and the other (M2) acts as an essential activator. RESULTS:
      Experiments in this communication characterize the interaction between M2 and
      Csk. Csk activity is sensitive to pH in the range of 6 to 7. Kinetic
      characterization indicates that the sensitivity is not due to altered substrate
      binding, but caused by the sensitivity of M2 binding to pH. Several residues in
      the active site with potential of binding M2 are mutated and the effect on metal
      activation studied. An active mutant of Asn319 is generated, and this mutation
      does not alter the metal binding characteristics. Mutations of Glu236 or Asp332
      abolish the kinase activity, precluding a positive or negative conclusion on
      their role in M2 coordination. Finally, the ability of divalent metal cations to
      activate Csk correlates to a combination of ionic radius and the coordination
      number. CONCLUSION: These studies demonstrate that M2 binding to Csk is sensitive
      to pH, which is mainly responsible for Csk activity change in the acidic arm of
      the pH response curve. They also demonstrate critical differences in the metal
      activator coordination sphere in protein tyrosine kinase Csk and a protein
      Ser/Thr kinase, the cAMP-dependent protein kinase. They shed light on the
      physical interactions between a protein tyrosine kinase and a divalent metal
      activator.

PMID- 16305748
TI  - Do proxies reflect patients' health concerns about urinary incontinence and gait
      problems?
AB  - BACKGROUND: While falls and urinary incontinence are prevalent among older
      patients, who sometimes rely on proxies to provide their health information, the
      validity of proxy reports of concern about falls and urinary incontinence remains
      unknown. METHODS: Telephone interviews with 43 consecutive patients with falls or
      fear of falling and/or bothersome urinary incontinence and their proxies chosen
      by patients as most knowledgeable about their health. The questionnaire included
      items derived from the Medical Outcomes Study Short Form 12 (SF-12), a scale
      assessing concerns about urinary incontinence (UI), and a measure of fear of
      falling, the Falls Efficacy Scale (FES). Scores were estimated using items asking
      the proxy perspective (6 items from the SF-12, 10 items from a UI scale, and all
      10 FES items). Proxy and patient scores were compared using intraclass
      correlation coefficients (ICC, one-way model). Variables associated with absolute
      agreement between patients and proxies were explored. RESULTS: Patients had a
      mean age of 81 years (range 75-93) and 67% were female while proxies had a mean
      age of 70 (range 42-87) and 49% were female. ICCs were 0.63 for the SF-12, 0.52
      for the UI scale, and 0.29 for the FES. Proxies tended to understate patients'
      general health and incontinence concern, but overstate patients' concern about
      falling. Proxies who lived with patients and those who more often see patients
      more closely reflected patient FES scores compared to those who lived apart or
      those who saw patients less often. Internal consistency reliability of proxy
      responses was 0.62 for the SF-12, 0.86 for the I-QOL, and 0.93 for the FES. In
      addition, construct validity of the proxy FES scale was supported by greater
      proxy-perceived fear of falling for patients who received medical care after a
      fall during the past 12 months (p < .05). CONCLUSION: Caution should be exercised
      when using proxies as a source of information about older patients' health
      perceptions. Questions asking about proxies' views yield suboptimal agreement
      with patient responses. However, proxy scales of UI and fall concern are
      internally consistent and may provide valid independent information.

PMID- 16305749
TI  - ASIC3, an acid-sensing ion channel, is expressed in metaboreceptive sensory
      neurons.
AB  - BACKGROUND: ASIC3, the most sensitive of the acid-sensing ion channels,
      depolarizes certain rat sensory neurons when lactic acid appears in the
      extracellular medium. Two functions have been proposed for it: 1) ASIC3 might
      trigger ischemic pain in heart and muscle; 2) it might contribute to some forms
      of touch mechanosensation. Here, we used immunocytochemistry, retrograde
      labelling, and electrophysiology to ask whether the distribution of ASIC3 in rat
      sensory neurons is consistent with either of these hypotheses. RESULTS: Less than
      half (40%) of dorsal root ganglion sensory neurons react with anti-ASIC3, and the
      population is heterogeneous. They vary widely in cell diameter and express
      different growth factor receptors: 68% express TrkA, the receptor for nerve
      growth factor, and 25% express TrkC, the NT3 growth factor receptor. Consistent
      with a role in muscle nociception, small (<25 microm) sensory neurons that
      innervate muscle are more likely to express ASIC3 than those that innervate skin
      (51% of small muscle afferents vs. 28% of small skin afferents). Over 80% of
      ASIC3+ muscle afferents co-express CGRP (a vasodilatory peptide). Remarkably few
      (9%) ASIC3+ cells express P2X3 receptors (an ATP-gated ion channel), whereas 31%
      express TRPV1 (the noxious heat and capsaicin-activated ion channel also known as
      VR1). ASIC3+/CGRP+ sensory nerve endings were observed on muscle arterioles, the
      blood vessels that control vascular resistance; like the cell bodies, the endings
      are P2X3- and can be TRPV1+. The TrkC+/ASIC3+ cell bodies are uniformly large,
      possibly consistent with non-nociceptive mechanosensation. They are not
      proprioceptors because they fail two other tests: ASIC3+ cells do not express
      parvalbumin and they are absent from the mesencephalic trigeminal nucleus.
      CONCLUSION: Our data indicates that: 1) ASIC3 is expressed in a restricted
      population of nociceptors and probably in some non-nociceptors; 2) co-expression
      of ASIC3 and CGRP, and the absence of P2X3, are distinguishing properties of a
      class of sensory neurons, some of which innervate blood vessels. We suggest that
      these latter afferents may be muscle metaboreceptors, neurons that sense the
      metabolic state of muscle and can trigger pain when there is insufficient oxygen.

PMID- 16305751
TI  - Computational identification of strain-, species- and genus-specific proteins.
AB  - BACKGROUND: The identification of unique proteins at different taxonomic levels
      has both scientific and practical value. Strain-, species- and genus-specific
      proteins can provide insight into the criteria that define an organism and its
      relationship with close relatives. Such proteins can also serve as taxon-specific
      diagnostic targets. DESCRIPTION: A pipeline using a combination of computational
      and manual analyses of BLAST results was developed to identify strain-, species-,
      and genus-specific proteins and to catalog the closest sequenced relative for
      each protein in a proteome. Proteins encoded by a given strain are preliminarily
      considered to be unique if BLAST, using a comprehensive protein database, fails
      to retrieve (with an e-value better than 0.001) any protein not encoded by the
      query strain, species or genus (for strain-, species- and genus-specific proteins
      respectively), or if BLAST, using the best hit as the query (reverse BLAST), does
      not retrieve the initial query protein. Results are manually inspected for
      homology if the initial query is retrieved in the reverse BLAST but is not the
      best hit. Sequences unlikely to retrieve homologs using the default BLOSUM62
      matrix (usually short sequences) are re-tested using the PAM30 matrix, thereby
      increasing the number of retrieved homologs and increasing the stringency of the
      search for unique proteins. The above protocol was used to examine several food-
      and water-borne pathogens. We find that the reverse BLAST step filters out about
      22% of proteins with homologs that would otherwise be considered unique at the
      genus and species levels. Analysis of the annotations of unique proteins reveals
      that many are remnants of prophage proteins, or may be involved in virulence. The
      data generated from this study can be accessed and further evaluated from the
      CUPID (Core and Unique Protein Identification) system web site (updated semi
      annually) at http://pir.georgetown.edu/cupid. CONCLUSION: CUPID provides a set of
      proteins specific to a genus, species or a strain, and identifies the most
      closely related organism.

PMID- 16305750
TI  - Multiple sequence alignment accuracy and evolutionary distance estimation.
AB  - BACKGROUND: Sequence alignment is a common tool in bioinformatics and comparative
      genomics. It is generally assumed that multiple sequence alignment yields better
      results than pair wise sequence alignment, but this assumption has rarely been
      tested, and never with the control provided by simulation analysis. This study
      used sequence simulation to examine the gain in accuracy of adding a third
      sequence to a pair wise alignment, particularly concentrating on how the
      phylogenetic position of the additional sequence relative to the first pair
      changes the accuracy of the initial pair's alignment as well as their estimated
      evolutionary distance. RESULTS: The maximal gain in alignment accuracy was found
      not when the third sequence is directly intermediate between the initial two
      sequences, but rather when it perfectly subdivides the branch leading from the
      root of the tree to one of the original sequences (making it half as close to one
      sequence as the other). Evolutionary distance estimation in the multiple
      alignment framework, however, is largely unrelated to alignment accuracy and
      rather is dependent on the position of the third sequence; the closer the branch
      leading to the third sequence is to the root of the tree, the larger the
      estimated distance between the first two sequences. CONCLUSION: The bias in
      distance estimation appears to be a direct result of the standard greedy
      progressive algorithm used by many multiple alignment methods. These results have
      implications for choosing new taxa and genomes to sequence when resources are
      limited.

PMID- 16305752
TI  - Characterization of 954 bovine full-CDS cDNA sequences.
AB  - BACKGROUND: Genome assemblies rely on the existence of transcript sequence to
      stitch together contigs, verify assembly of whole genome shotgun reads, and
      annotate genes. Functional genomics studies also rely on transcript sequence to
      create expression microarrays or interpret digital tag data produced by methods
      such as Serial Analysis of Gene Expression (SAGE). Transcript sequence can be
      predicted based on reconstruction from overlapping expressed sequence tags (EST)
      that are obtained by single-pass sequencing of random cDNA clones, but these
      reconstructions are prone to errors caused by alternative splice forms,
      transcripts from gene families with related sequences, and expressed pseudogenes.
      These errors confound genome assembly and annotation. The most useful transcript
      sequences are derived by complete insert sequencing of clones containing the
      entire length, or at least the full protein coding sequence (CDS) portion, of the
      source mRNA. While the bovine genome sequencing initiative is nearing completion,
      there is currently a paucity of bovine full-CDS mRNA and protein sequence data to
      support bovine genome assembly and functional genomics studies. Consequently, the
      production of high-quality bovine full-CDS cDNA sequences will enhance the bovine
      genome assembly and functional studies of bovine genes and gene products. The
      goal of this investigation was to identify and characterize the full-CDS
      sequences of bovine transcripts from clones identified in non-full-length
      enriched cDNA libraries. In contrast to several recent full-length cDNA
      investigations, these full-CDS cDNAs were selected, sequenced, and annotated
      without the benefit of the target organism's genomic sequence, by using
      comparison of bovine EST sequence to existing human mRNA to identify likely full
      CDS clones for full-length insert cDNA (FLIC) sequencing. RESULTS: The predicted
      bovine protein lengths, 5' UTR lengths, and Kozak consensus sequences from 954
      bovine FLIC sequences (bFLICs; average length 1713 nt, representing 762 distinct
      loci) are all consistent with previously sequenced mammalian full-length
      transcripts. CONCLUSION: In most cases, the bFLICs span the entire CDS of the
      genes, providing the basis for creating predicted bovine protein sequences to
      support proteomics and comparative evolutionary research as well as functional
      genomics and genome annotation. The results demonstrate the utility of the
      comparative approach in obtaining predicted protein sequences in other species.

PMID- 16305753
TI  - Analysis of vertebrate genomes suggests a new model for clade B serpin evolution.
AB  - BACKGROUND: The human genome contains 13 clade B serpin genes at two loci, 6p25
      and 18q21. The three genes at 6p25 all conform to a 7-exon gene structure with
      conserved intron positioning and phasing, however, at 18q21 there are two 7-exon
      genes and eight genes with an additional exon yielding an 8-exon structure.
      Currently, it is not known how these two loci evolved, nor which gene structure
      arose first--did the 8-exon genes gain an exon, or did the 7-exon genes lose one?
      Here we use the genomes of diverse vertebrate species to plot the emergence of
      clade B serpin genes and to identify the point at which the two genomic
      structures arose. RESULTS: Analysis of the chicken genome indicated the presence
      of a single clade B serpin gene locus, containing orthologues of both human loci
      and both genomic structures. The frog genome and the genomes of three fish
      species presented progressively simpler loci, although only the 7-exon structure
      could be identified. The Serpinb12 gene contains seven exons in the frog genome,
      but eight exons in chickens and humans, indicating that the additional exon
      evolved in this gene. CONCLUSION: We propose a new model for clade B serpin
      evolution from a single 7-exon gene (either Serpinb1 or Serpinb6). An additional
      exon was gained in the Serpinb12 gene between the tetrapoda and amniota
      radiations to produce the 8-exon structure. Both structures were then duplicated
      at a single locus until a chromosomal breakage occurred at some point along the
      mammalian lineage resulting in the two modern loci.

PMID- 16305754
TI  - Immunome research.
AB  - Immunology research has been transformed in the post-genomics era, with high
      throughput molecular biology and information technologies taking an increasingly
      central role. This has led to the development of a new area of science termed
      "Immunomics", that encompasses genomic, high throughput and bioinformatic
      approaches to immunology. In recognition of the increasing importance of this
      field, Immunome Research is a new Open Access, online journal, that will publish
      cutting edge research across the field of Immunomics. Immunome Research will
      publish a wide range of article types including specialty immunology databases,
      immunology database tools, immunome epitope research, epitope analysis tools,
      high-throughput technologies (gene sequencing, microarrays, proteomics), white
      papers, mathematical and theoretical models, and prediction tools. Immunome
      Research is the official journal of the International Immunomics Society (IIMMS).

PMID- 16305755
TI  - An ontology for immune epitopes: application to the design of a broad scope
      database of immune reactivities.
AB  - BACKGROUND: Epitopes can be defined as the molecular structures bound by specific
      receptors, which are recognized during immune responses. The Immune Epitope
      Database and Analysis Resource (IEDB) project will catalog and organize
      information regarding antibody and T cell epitopes from infectious pathogens,
      experimental antigens and self-antigens, with a priority on NIAID Category A-C
      pathogens (http://www2.niaid.nih.gov/Biodefense/bandc_priority.htm) and
      emerging/re-emerging infectious diseases. Both intrinsic structural and
      phylogenetic features, as well as information relating to the interactions of the
      epitopes with the host's immune system will be catalogued. DESCRIPTION: To
      effectively represent and communicate the information related to immune epitopes,
      a formal ontology was developed. The semantics of the epitope domain and related
      concepts were captured as a hierarchy of classes, which represent the general and
      specialized relationships between the various concepts. A complete listing of
      classes and their properties can be found at
      http://www.immuneepitope.org/ontology/index.html. CONCLUSION: The IEDB's ontology
      is the first ontology specifically designed to capture both intrinsic chemical
      and biochemical information relating to immune epitopes with information relating
      to the interaction of these structures with molecules derived from the host
      immune system. We anticipate that the development of this type of ontology and
      associated databases will facilitate rigorous description of data related to
      immune epitopes, and might ultimately lead to completely new methods for
      describing and modeling immune responses.

PMID- 16305756
TI  - Modelling vaccination schedules for a cancer immunoprevention vaccine.
AB  - We present a systematic approach to search for an effective vaccination schedule
      using mathematical computerized models. Our study is based on our previous model
      that simulates the cancer vs immune system competition activated by tumor
      vaccine. This model accurately reproduces in-vivo experiments results on HER
      2/neu mice treated with the immuno-prevention cancer vaccine (Triplex) for
      mammary carcinoma. In vivo experiments have shown the effectiveness of Triplex
      vaccine in protection of mice from mammary carcinoma. The full protection was
      conferred using chronic (prophylactic) vaccination protocol while therapeutic
      vaccination was less efficient. In the present paper we use the computer
      simulations to systematically search for a vaccination schedule which prevents
      solid tumor formation. The strategy we used for defining a successful vaccination
      schedule is to control the number of cancer cells with vaccination cycles. We
      found that, applying the vaccination scheme used in in-vivo experiments, the
      number of vaccine injections can be reduced roughly by 30%.

PMID- 16305760
TI  - [Early diagnosis and treatment of rheumatoid arthritis].

PMID- 16305757
TI  - AntiJen: a quantitative immunology database integrating functional,
      thermodynamic, kinetic, biophysical, and cellular data.
AB  - AntiJen is a database system focused on the integration of kinetic,
      thermodynamic, functional, and cellular data within the context of immunology and
      vaccinology. Compared to its progenitor JenPep, the interface has been completely
      rewritten and redesigned and now offers a wider variety of search methods,
      including a nucleotide and a peptide BLAST search. In terms of data archived,
      AntiJen has a richer and more complete breadth, depth, and scope, and this has
      seen the database increase to over 31,000 entries. AntiJen provides the most
      complete and up-to-date dataset of its kind. While AntiJen v2.0 retains a focus
      on both T cell and B cell epitopes, its greatest novelty is the archiving of
      continuous quantitative data on a variety of immunological molecular
      interactions. This includes thermodynamic and kinetic measures of peptide binding
      to TAP and the Major Histocompatibility Complex (MHC), peptide-MHC complexes
      binding to T cell receptors, antibodies binding to protein antigens and general
      immunological protein-protein interactions. The database also contains
      quantitative specificity data from position-specific peptide libraries and
      biophysical data, in the form of diffusion co-efficients and cell surface copy
      numbers, on MHCs and other immunological molecules. The uses of AntiJen include
      the design of vaccines and diagnostics, such as tetramers, and other laboratory
      reagents, as well as helping parameterize the bioinformatic or mathematical in
      silico modeling of the immune system. The database is accessible from the URL:
      http://www.jenner.ac.uk/antijen.

PMID- 16305761
TI  - [Generalised joint hypermobility and benign joint hypermobility syndrome. I:
      reproducibility and validity of tests and criteria].
AB  - The clinician's evaluation of the presence of joint hypermobility is most often
      performed through application of a joint mobility scoring system. Several systems
      are available, all of them based on tests of selected joints or movements. In
      most cases, a positive test is based on a range of motion at or above the mean
      range of motion +3 SD. The tests' reproducibility is good when performed by an
      experienced rheumatologist; however, their validity is unknown as there are no
      gold standards. The British Society of Rheumatology has recommended Beighton's
      scoring system and the level > or =4 positive tests out of 9 as the criterion for
      general hypermobility. The reproducibility of the criterion has been examined
      only once, and only with the cut level of > or =6/9 tests. At this level, the
      intra- and interobserver variability was 0.75 and 0.78, respectively. In another
      study it was demonstrated that the Beighton scoring system correlates well with a
      global joint mobility index and shows good agreement with two other scoring
      systems. The diagnostic specificity is poor with regard to the criteria for
      benign joint hypermobility syndrome.

PMID- 16305762
TI  - [Generalised joint hypermobility and benign joint hypermobility syndrome. II:
      epidemiology and clinical criteria].
AB  - Gender-, age- and race-related generalised joint hypermobility (GJH) is
      elucidated, based on publications that have used validated criteria for GJH.
      Furthermore, we analysed the connection between GJH and the clinical criteria for
      benign joint hypermobility syndrome (BJHS), and we looked for literature on the
      treatment of BJHS. There seems to be evidence in support of an increased
      prevalence of hypermobility among children, females and certain races when the
      diagnosis of hypermobility is based on the Carter and Wilkinson criteria (> or =3
      positive tests out of 5) and/or Beighton's tests (> or =4 positive tests out of
      9). However, there are no unequivocal statements that hypermobility predisposes
      to the various clinical situations used as major or minor criteria for BJHS,
      e.g., arthralgia, low back and pelvic pain, joint luxation, soft tissue
      rheumatism, abnormal cutis or genitourinary prolapse, varicose veins and hernia.
      There have been no randomised controlled studies of the effect of treatment.

PMID- 16305763
TI  - [Examination and treatment of orthopedic-surgery patients with osteoporosis
      related fragility fractures].
AB  - To reduce the future risk of fracture, we recommend that patients treated for
      fragility fractures (FF) in the OPD be given vitamin D (20 mcg OD) and calcium
      (1200 mg OD) until the fracture has healed, be counseled on the possible relation
      of their fracture to osteoporosis (OPO) and contact their GP for examination.
      Patients with FF of the hip may also be treated with vitamin D and calcium and
      screened for secondary OPO. If screening tests are negative and life expectancy
      is greater than two years, a measurement of bone mineral density is not necessary
      before the start of treatment with bisphosphonate.

PMID- 16305764
TI  - [Osteoarthritis, the most common joint problem].

PMID- 16305765
TI  - [Early referral and treatment of patients with acute arthritis. Experiences from
      two early arthritis clinics].
AB  - INTRODUCTION: Our aim was to describe the referral pattern among patients
      admitted to early arthritis clinics (EAC) in the counties of Funen and South
      Jutland, Denmark. MATERIALS AND METHODS: In order to accelerate the diagnostic
      workup of patients with suspected rheumatoid arthritis (RA), general
      practitioners, rheumatology specialists and neighbouring hospital departments
      were invited to refer to the EAC patients who had synovitis in at least one joint
      lasting more than 6 weeks but less than 12 months. RESULTS: 226 patients were
      admitted. The median total lag time from onset of joint complaints to visiting
      the EAC was 89 days (IQ 57-154). The average lag time between receipt of the
      referral to the first visit to the EAC was 18 days (IQ 5-31). 91 (40%) of the
      patients had synovitis upon clinical examination. 51 (23%) of these fulfilled the
      ACR 1987 classification criteria for RA, and 40 (17%) had synovitis of other
      aetiologies than RA. Compared with non-RA patients, the RA subset was
      characterised by older age, female preponderance, higher joint counts and
      disability and a more pronounced acute phase response. Despite the short duration
      of the disease, 17% of the RA patients had X-ray erosions. DISCUSSION: In spite
      of the rigid criteria for referral to the EAC, synovitis was demonstrated by
      clinical examination in only 40% of the patients. Half of these were classified
      as RA. The total median lag time of three months from the onset of joint symptoms
      to the first visit to the EAC accords with current recommendations. Standardised
      criteria for referral to EACs should be prepared and combined with educational
      efforts to improve joint assessment skills.

PMID- 16305766
TI  - [E-mail communication in general practice].
AB  - INTRODUCTION: Our aim was to examine how e-mail communication in general practice
      affects the doctor/patient relationship and doctors' workload. MATERIALS AND
      METHODS: Registration was done of e-mail activity in three Danish GP surgeries
      over a period of 12 months and focus group interviews with patients and doctors.
      RESULTS: The practices received 191 e-mails per 1,000 patients per year. The
      male/female ratio was 0.9 to 1. The average patient age was 47.2 years; the
      oldest user was 88 years old. Qualitative data were categorized under various
      headings, such as need, expectations, usability, workload, patient service, the
      communication part of professionalism, worries and barriers against use.
      DISCUSSION: E-mail is a requested and useful communication form between doctors
      and patients in general practice. But it requires guidance and structured
      communication. It works best when the doctor and patient know each other. It is
      being used less than might be expected. The barriers from patients' point of view
      are lack of knowledge of and access to computers, lack of awareness of the
      possibility of contacting the physician by e-mail and the absence of a personal
      invitation for use by the personal physician. It is a matter of concern that
      patients apparently don't read the recommendations concerning proper use of e
      mail communication, even though they are clearly described on the Web site and
      patients have to click "has been read" to be able to continue.

PMID- 16305767
TI  - [Advanced prehospital care in patients with life-threatening conditions--survival
      rate, health status and functional level].
AB  - INTRODUCTION: In Aarhus, Denmark, advanced prehospital care was carried out by
      anaesthetists working in a rendezvous model with ordinary ambulances. The effect
      on the patient was evaluated by the physician on scene. The purpose of the study
      was to evaluate survival rate, health status and functional level in patients
      after lifesaving prehospital care. MATERIALS AND METHODS: Consecutive data were
      reported to a prehospital database and the National Patient Registry. Data on
      survival from 1998 to 2000 were retrieved. Functional level was studied in
      lifesaving cases in the year 2000. We interviewed the general practitioners (GPs)
      involved according to EuroQol. The EuroQol interview concerned health status and
      function level. RESULTS: In 1998-2000, prehospital anaesthetists attended a total
      of 11,684 patients. Treatment was described as lifesaving in 238 (2%) of the
      cases, and 63% of the patients (151/238) were alive one year later. In the year
      2000, 79 patients were identified as having had lifesaving treatment, and 48 were
      alive one year later; 67% (32/48) were without functional impairment according to
      EuroQol. The most frequent diagnoses were self-intoxication and cardiovascular
      and respiratory diseases. CONCLUSION: Lifesaving prehospital care, as evaluated
      by the prehospital physician on scene, was performed in 2 percent of all cases
      attended by a prehospital anaesthetist. Of these patients, the majority were
      alive after one year and without functional impairment, according to their GP.
      The diagnoses were varied.

PMID- 16305768
TI  - [Forensic patients in Denmark--2000-2004].
AB  - INTRODUCTION: In Denmark the number of forensic patients increased exponentially
      from 1980 to 1999, with an annual growth rate of 6.8%. In 2000 some psychiatric
      orders became time-limited. This study maps out the development from 2000 to
      2004. MATERIALS AND METHODS: The material includes forensic patients under
      supervision by a probation officer. Since 1977, the Department of Prisons and
      Probation has registered their prevalence and, since 1989, also the incidence and
      the lifting of previously established orders. The material is representative and
      has been corrected according to new legislation. The monthly prevalence is
      analysed 1980-2004, the monthly incidence 1989-2004. RESULTS: The incidence
      increased exponentially from 1989 to 1999, with an annual growth rate of 6.2%,
      the annual growth rate from 2002 to 2004 being 12.8% (p=0.078). The whole period
      1989-2004 showed a constantly increasing growth rate (p<0.001). The prevalence
      decreased from 2000 to 2001, as many orders were lifted due to new legislation.
      The prevalence in 2002-2004 shows an annual growth rate of 11.0%. The difference
      between the growth rates of incidence and prevalence 2002-2004 is not
      significant. Thus the number of forensic patients is now increasing
      exponentially, with an annual growth rate of 11% CONCLUSION: Increasing
      criminality among schizophrenic patients has been established in many countries.
      The main reason is supposed to be deinstitutionalization, which probably applies
      to Denmark as well. Today forensic patients occupy about 20% of the total number
      of psychiatric beds in Denmark, and whatever the reasons for the growing number
      are, this fact, in combination with the decreasing number of available beds,
      points towards a disastrous development for the mentally ill.

PMID- 16305769
TI  - [The significance of dressings and topical agents for surgical wounds healing by
      secondary intention].

PMID- 16305770
TI  - [Testicular torsion after previous fixation of the testis].
AB  - Testicular torsion (TT) is caused by rotation of the testis. If not treated
      acutely, TT causes ischaemic necrosis. As the anatomic variations responsible for
      the torsion are likely to be bilateral, the opposite testis should also be fixed.
      We report on a case where a patient was admitted to hospital with clinical signs
      of TT. Two years earlier the patient had undergone fixation of the testis in an
      operation for TT on the opposite side. Patients with clinical signs of TT should
      be explored even if both testis have previously been fixed.

PMID- 16305771
TI  - [Picture of the month: echocardiography].

PMID- 16305772
TI  - [The H-index, a smart bibliometric parameter].

PMID- 16305782
TI  - [Unfortunate packaging of paracetamol mixture].

PMID- 16305783
TI  - [Chlamydia among children and adolescents].

PMID- 16305784
TI  - [Treatment of juvenile angiofibromas].

PMID- 16305787
TI  - [Nurse practitioners--something for us?].

PMID- 16305793
TI  - What does Batman think about SpongeBob? children's understanding of the
      fantasy/fantasy distinction.
AB  - Young children reliably distinguish reality from fantasy; they know that their
      friends are real and that Batman is not. But it is an open question whether they
      appreciate, as adults do, that there are multiple fantasy worlds. We test this by
      asking children and adults about fictional characters' beliefs about other
      characters who exist either within the same world (e.g., Batman and Robin) or in
      different worlds (e.g., Batman and SpongeBob). Study 1 found that although both
      adults and young children distinguish between within-world and across-world types
      of character relationships, the children make an unexpected mistake: they often
      claim that Batman thinks that Robin is make believe. Study 2 used a less explicit
      task, exploring intuitions about the actions of characters-whom they could see,
      touch, and talk to--and found that children show a mature appreciation of the
      ontology of fictional worlds.

PMID- 16305794
TI  - Handling outliers in brain tumour MRS data analysis through robust topographic
      mapping.
AB  - Uncertainty is inherent in medical decision making and poses a challenge for
      intelligent technologies. This paper focuses on magnetic resonance spectra (MRS)
      for discrimination of brain tumour types and grades. Modelling of this type of
      high-dimensional data is commonly affected by uncertainty caused by the presence
      of outliers. Multivariate data clustering and visualization of MRS data is
      proposed using the GTM framework with basis functions comprising Student t
      distributions in order to minimize the negative impact on the model from
      outliers. The effectiveness of this model on the MRS data is demonstrated
      empirically.

PMID- 16305795
TI  - Effect of diabetes on the mechanisms of intrathecal antinociception of sildenafil
      in rats.
AB  - The mechanism of intrathecal antinociceptive action of the phosphodiesterase 5
      inhibitor sildenafil was assessed in diabetic rats using the formalin test.
      Intrathecal administration of sildenafil (12.5-50 microg) produced a dose-related
      antinociception during both phases of the formalin test in non-diabetic and
      diabetic rats. Intrathecal pretreatment with N-L-nitro-arginine methyl ester (L
      NAME, nitric oxide (NO) synthase inhibitor, 1-50 microg), 1H-(1,2,4)
      oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, guanylyl cyclase inhibitor, 1-10 microg),
      KT5823 (protein kinase G (PKG) inhibitor, 5-500 ng), charybdotoxin (large
      conductance Ca2+-activated K+ channel blocker, 0.01-1 ng), apamin (small
      conductance Ca2+-activated K+ channel blocker, 0.1-3 ng) and glibenclamide (ATP
      sensitive K+ channel blocker, 12.5-50 microg), but not N-D-nitro-arginine methyl
      ester (D-NAME, 50 microg) or saline, significantly diminished sildenafil (50
      microg)-induced antinociception in non-diabetic rats. Intrathecal administration
      of ODQ, KT5823, apamin and glibenclamide, but not L-NAME nor charybdotoxin,
      reversed intrathecal antinociception induced by sildenafil in diabetic rats.
      Results suggest that sildenafil produces its intrathecal antinociceptive effect
      via activation of NO-cyclic GMP-PKG-K+ channels pathway in non-diabetic rats.
      Data suggest that diabetes leads to a dysfunction in NO and large-conductance
      Ca2+-activated K+ channels. Sildenafil could have a role in the pharmacotherapy
      of diabetes-associated pain.

PMID- 16305796
TI  - Estriol, conjugated equine estrogens, and alendronate therapy for osteoporosis.

PMID- 16305797
TI  - Development and validation of an antigen-binding capture ELISA for native and
      putrescine-modified anti-tetanus F(ab')2 fragments for the assessment of the
      cellular uptake and plasma kinetics of the antibodies.
AB  - Cationization is a strategy to enhance the permeability of antibodies to
      physiological membranes for potential therapeutic and diagnostic applications of
      these proteins, with one of its crucial points being the retention of antigen
      binding activity. Here, we describe the cationization of horse polyclonal anti
      tetanus F(ab')(2) fragments and the development and validation of an ELISA for
      quantitative measurements of the binding activity of the native and cationized
      F(ab')(2) in cell lysates and rat plasma samples, assessing the cellular uptake
      and plasma kinetics of these antibodies, respectively. The method used tetanus
      anatoxin coated on microtitre plates as capture antigen to bind sample or
      standard F(ab')(2), the amount of antibody binding being quantified using, first,
      a secondary biotinylated anti-horse antibody/streptavidin-alkaline phosphatase
      complex in situ and then a measurement of the substrate product. Cationization of
      the F(ab')(2) was performed with putrescine at pH 4.5 using soluble carbodiimide
      as carboxyl activator. The average substitution ratio was determined at 3
      putrescine molecules per F(ab')(2) molecule. The cationized F(ab')(2) retained
      roughly 80% of the initial antigen binding activity and was stable over a 1 year
      period of storage at -20 degrees C. The ELISA validation data showed that the
      method was linear for both the native and cationized F(ab')(2) using Hanks'
      balanced saline solution with 0.2% bovine serum albumin as assay diluent for the
      cell lysate samples. The useful F(ab')(2) concentration range was 2.5-25 ng/ml
      and the limit of quantification was 2.5 ng/ml. With rat blank plasma used as
      assay diluent for the rat plasma samples the useful F(ab')(2) concentration range
      was 3.5-25 ng/ml and the limit of quantification was 3.5 ng/ml. Specific
      requirements for the limits of quantification were fulfilled: precision < or =20%
      CV and accuracy within +/-20% of the nominal values. Intra- and inter-assay
      coefficients of variation were within 9% and accuracies within +/-10% of the
      nominal values. The validated method was applied to the study of the cellular
      uptake of native and cationized anti-tetanus F(ab')(2) in an HL 60 cell model,
      and of plasma kinetics after i.v. administration to rats.

PMID- 16305798
TI  - Impact of saliva collection methods on sIgA and cortisol assays and acceptability
      to participants.
AB  - In community-based studies of stress and immunity, saliva samples offer a non
      intrusive way of gathering biological data. Cotton-based devices are widely used
      in cortisol research, but some may affect assay results. We compared assay
      reliability and perceived acceptability of three saliva collection methods:
      passive, cotton 'salivettes' and cellulose-cotton tip 'eyespears'. Compared to
      passive collection, salivettes reduced the concentration of cortisol (p = .001)
      and sIgA (p = .002). Eyespears did not reduce cortisol or sIgA concentration, and
      showed less interference in the rank ordering of cortisol (r(eyespear with
      passive) = .90) and sIgA scores (r(eyespear with passive) = .96) compared to
      salivettes (r cortisol(salivette with passive) = .79; r sIgA(salivette with
      passive) = .66). The comfort and acceptability of both cotton-based devices were
      rated positively. Cotton-cellulose eyespears could offer methodological
      advantages for collecting saliva to measure cortisol and sIgA levels, and,
      because they can be held during sampling, may be useful for research with
      children and the frail elderly.

PMID- 16305799
TI  - Archaeal RNA polymerase is sensitive to intrinsic termination directed by
      transcribed and remote sequences.
AB  - Archaea are prokaryotes with a single DNA-dependent RNA polymerase (RNAP) that is
      homologous to, and likely resembles the ancestor of all three eukaryotic RNAPs.
      In vitro studies have confirmed that initiation by archaeal RNAPs resembles the
      Pol II system, and we report the first detailed in vitro investigation of
      archaeal transcription termination. Methanothermobacter thermautotrophicus (M.t.)
      RNAP is susceptible to intrinsic termination at an intergenic sequence that
      conforms to a bacterial intrinsic terminator, as well as at bona fide bacterial
      intrinsic terminators. In contrast to bacterial RNAPs, M.t. RNAP also terminated
      in response to synthetic and natural oligo-T-rich sequences that were not
      preceded by sequences with any recognizable potential to form a stable RNA
      hairpin. Both template topology and temperature influenced the position and
      extent of termination in vitro, and the results argue that transcription of an
      upstream sequence can alter the termination response of the archaeal RNAP at a
      remote downstream sequence.

PMID- 16305800
TI  - Crystal structure of human BACE2 in complex with a hydroxyethylamine transition
      state inhibitor.
AB  - BACE2 is a membrane-bound aspartic protease of the A1 family with a high level of
      sequence homology to BACE1. While BACE1 is involved in the generation of amyloid
      plaques in Alzheimer's disease by cleaving Abeta-peptides from the amyloid
      precursor protein, the physiological function of BACE2 is not well understood.
      BACE2 appears to be associated with the early onset of dementia in patients with
      Down's syndrome, and it has been shown to be highly expressed in breast cancers.
      Further, it may participate in the function of normal and abnormal processes of
      human muscle biology. Similar to other aspartic proteases, BACE2 is expressed as
      an inactive zymogen requiring the cleavage of its pro-sequence during the
      maturation process. We have produced mature BACE2 by expression of pro-BACE2 in
      Escherichia coli as inclusion bodies, followed by refolding and autocatalytic
      activation at pH 3.4. Using a C and N-terminally truncated BACE2 variant, we were
      able to crystallize and determine the crystal structure of mature BACE2 in
      complex with a hydroxyethylamine transition-state mimetic inhibitor at 3.1
      angstroms resolution. The structure of BACE2 follows the general fold of A1
      aspartic proteases. However, similar to BACE1, its C-terminal domain is
      significantly larger than that of the other family members. Furthermore, the
      structure of BACE2 reveals differences in the S3, S2, S1' and S2' active site
      substrate pockets as compared to BACE1, and allows, therefore, for a deeper
      understanding of the structural features that may facilitate the design of
      selective BACE1 or BACE2 inhibitors.

PMID- 16305801
TI  - Entropically driven MHC class I recognition by human inhibitory receptor
      leukocyte Ig-like receptor B1 (LILRB1/ILT2/CD85j).
AB  - The human inhibitory receptor, leukocyte immunoglobulin (Ig)-like receptor B1
      (also called Ig-like transcript (ILT) 2, CD85j), is broadly expressed on
      leukocytes. LILRB1 binds to a wide range of major histocompatibility complex
      class I molecules (MHCIs) and transduces negative signals that can, for example,
      prevent killing of MHCI-expressing cells. Here we report the kinetic,
      thermodynamic, NMR and crystallographic analyses of MHCI recognition by LILRB1.
      Kinetic studies demonstrated that LILRB1 binds to MHCIs with fast association and
      dissociation rates, typical of cell-cell recognition receptors. Thermodynamic
      analyses showed that LILRB1-MHCI interactions are entropically driven (-TdeltaS =
      -9.4 approximately -6.6 kcal mol(-1)) with low heat capacity changes (deltaC(p) =
      -0.22 approximately -0.10 kcal mol(-1) K(-1)). The crystal structures of LILRB1
      in the different crystal forms exhibited variation in the elbow angle between the
      two N-terminal Ig-like domains, indicating interdomain flexibility. Consistently,
      NMR analysis provided the direct evidence of the conformational changes of LILRB1
      upon the MHCI binding. These findings suggest that LILRB1-MHCI interactions,
      while involving some conformational adjustment, are not accompanied by a very
      large reduction in conformational flexibility at the binding interface. This mode
      of binding is distinct from "induced-fit" binding, which is associated with large
      reductions in conformational flexibility, and would be suitable for rapid
      engagement of MHCIs to enable fast monitoring of the expression level of MHCIs on
      target cells.

PMID- 16305802
TI  - Gold nanocluster formation using metallothionein: mass spectrometry and electron
      microscopy.
AB  - Clonable contrasting agents for light microscopy, such as green fluorescent
      protein, have revolutionized biology, but few such agents have been developed for
      transmission electron microscopy (TEM). As an attempt to develop a novel clonable
      contrasting agent for TEM, we have evaluated metallothionein, a small metal
      binding protein, reacted with aurothiomalate, an anti-arthritic gold compound.
      Electro spray ionization and matrix-assisted laser desorption/ionization (MALDI)
      mass spectrometry measurements show a distribution of gold atoms bound to
      individual metallothionein molecules. Unlike previous reports, these data show
      gold binding occurred as the addition of single atoms without retention of
      additional ligands. Moreover, under certain conditions, MALDI spectra show gold
      binding ratios of greater than 1:1 with the cysteine residues of metallothionein.
      Together, this may hint at a gold-binding mechanism similar to gold nanocluster
      formation. Finally, metallothionein-gold complexes visualized in the TEM show a
      range of sizes similar to those used as current TEM labels, and show the
      potential of the protein as a clonable TEM label in which the gold cluster is
      grown on the label, thereby circumventing the problems associated with attaching
      gold clusters.

PMID- 16305803
TI  - MDOC and atorvastatin have potential antiinflammatory effects in vascular
      endothelium of apoE-/- mouse model of atherosclerosis.
AB  - Members of the immunoglobulin superfamily of endothelial adhesion molecules,
      vascular cell adhesion molecule (VCAM-1) and intercellular cell adhesion molecule
      (ICAM- 1), strongly participate in leukocyte adhesion to the endothelium and play
      an important role in all stages of atherogenesis. The aim of this study was to
      detect and quantify the changes of endothelial expression of VCAM-1, and ICAM-1
      in the vessel wall after the short-term administration of simvastatin,
      atorvastatin, and micro dispersed derivatives of oxidised cellulose (MDOC) in
      apolipoprotein-E-deficient (apoE(-/-)) mice atherosclerotic model. Hyperlipidemic
      apoE(-/-) mice (n = 32) received normal chow diet or diet containing simvastatin
      or atorvastatin 10 mg/kg/day or MDOC 50 mg/kg/day. Total cholesterol, VLDL, LDL,
      HDL and TAG were measured and the endothelial expression of VCAM-1 and ICAM-1 was
      visualized and quantified by means of immunohistochemistry and stereology,
      respectively. Total cholesterol levels was insignificantly lowered only in MDOC
      treated mice but not in mice treated with statins. ICAM-1 endothelial expression
      was not affected by neither simvastatin nor MDOC treatment. However, significant
      diminution of VCAM-1 endothelial expression was observed in both atorvastatin and
      MDOC treated mice. These results provide new information of potential
      hypolipidemic substance MDOC and its potential anti-inflammatory effects.
      Furthermore, we have confirmed anti-inflammatory effects of atorvastatin
      independent of plasma cholesterol lowering. Thus, the results of this study show
      potential benefit of both MDOC and atorvastatin treatment in apoE(-/-) mouse
      model of atherosclerosis suggesting their possible combination might be of
      interest.

PMID- 16305804
TI  - CD16+ monocytes exposed to HIV promote highly efficient viral replication upon
      differentiation into macrophages and interaction with T cells.
AB  - The CD16+ subset of monocytes is dramatically expanded in peripheral blood during
      progression to AIDS, but its contribution to HIV pathogenesis is unknown. Here,
      we demonstrate that CD16+ but not CD16- monocytes promote high levels of HIV
      replication upon differentiation into macrophages and interaction with T cells.
      Conjugates formed between CD16+ monocyte-derived macrophages and T cells are
      major sites of viral replication. Furthermore, similar monocyte-T cell conjugates
      detected in peripheral blood of HIV-infected patients harbor HIV DNA. Thus,
      expansion of CD16+ monocytes during HIV infection and their subsequent
      recruitment into tissues such as lymph nodes, brain, and intestine may contribute
      to HIV dissemination and establishment of productive infection in T cells.

PMID- 16305805
TI  - Rational development of GAG-augmented chitosan membranes by fractional factorial
      design methodology.
AB  - To develop a novel biomaterial for chondrocyte culture, 8 glycosaminoglycan
      (GAG)/chitosan membranes (groups N1-N8) were prepared, with the aid of a 2-level
      2(4-1) fractional factorial design, by co-immobilizing chondroitin-4-sulfate
      (CSA), chondroitin-6-sulfate (CSC), dermatan sulfate (DS), and heparin to
      chitosan membranes. The fractional factorial design allowed us to partly
      interpret the effects of individual GAGs and two-way interactions between GAGs.
      Within the level range of -1 and +1, low CSA level (2.6 mg) is favorable for
      collagen synthesis but not for cell proliferation. High CSC level (1.3 mg) is
      favorable for GAG production but not for cell proliferation. Conversely, high
      heparin (0.33 mg) and DS (0.13 mg) levels are desired for cell proliferation but
      not for the production of collagen and GAG. Moreover, the two-way interactions
      between GAGs influence the cell behavior. Among the 8 GAG/chitosan membranes, N1
      and N4 (containing low CSA and heparin levels) lead to the maintenance of proper
      chondrocyte phenotype, as judged by the chondrocyte-like morphology, modest cell
      expansion, higher GAG and collagen production and proper cartilage marker gene
      expression. In conclusion, this approach provides a means of rationally
      predicting and evaluating the proper formulation of GAG/chitosan membranes and
      may facilitate the rational design of other tissue engineering scaffolds.

PMID- 16305806
TI  - Controlled release of heparin from poly(epsilon-caprolactone) electrospun fibers.
AB  - Sustained delivery of heparin to the localized adventitial surface of grafted
      blood vessels has been shown to prevent the vascular smooth muscle cell (VSMC)
      proliferation that can lead to graft occlusion and failure. In this study heparin
      was incorporated into electrospun poly(epsilon-caprolactone) (PCL) fiber mats for
      assessment as a controlled delivery device. Fibers with smooth surfaces and no
      bead defects could be spun from polymer solutions with 8%w/v PCL in 7:3
      dichloromethane:methanol. A significant decrease in fiber diameter was observed
      with increasing heparin concentration. Assessment of drug loading, and imaging of
      fluorescently labeled heparin showed homogenous distribution of heparin
      throughout the fiber mats. A total of approximately half of the encapsulated
      heparin was released by diffusional control from the heparin/PCL fibers after 14
      days. The fibers did not induce an inflammatory response in macrophage cells in
      vitro and the released heparin was effective in preventing the proliferation of
      VSMCs in culture. These results suggest that electrospun PCL fibers are a
      promising candidate for delivery of heparin to the site of vascular injury.

PMID- 16305807
TI  - The in vitro hydrolysis of poly(ester urethane)s consisting of poly[(R)-3
      hydroxybutyrate] and poly(ethylene glycol).
AB  - This paper reports the study of the complete degradation process for a series of
      newly synthesized multi-block poly(ester urethane)s consisting of poly[(R)-3
      hydroxybutyrate] (PHB) as hard and hydrophobic block and poly(ethylene glycol)
      (PEG) as soft and hydrophilic segment. The initial stages of degradation of the
      poly(PHB/PEG urethane)s were monitored by carrying out the degradation
      experiments at pH 7.4 and 37 degrees C. The weight loss of the copolymer films
      was traced, and the degraded copolymer films were characterized by GPC, (1)H NMR,
      TGA, and SEM. The induction phase of the polymer degradation was characterized by
      a random chain scission of the ester backbone bonds of the PHB segments and an
      insignificant decline in the weight of the polymer films. An accelerated
      degradation process was carried out at pH 11.5 and 37 degrees C to investigate
      the long-term degradation behaviour. The characterization of the degraded polymer
      films was similar to that for the experiment at pH 7.4. In addition, the water
      soluble degradation products were characterized by GPC, (1)H NMR, and FTIR. The
      main components of the water-soluble degradation products were found to be PEG
      blocks (monomeric up to quadmeric), 3-hydroxybutyric acid, and crotonic acid. It
      was found that the copolymer incorporating the highest amount of PEG degraded at
      the highest rate of all the copolymers studied. The complete degradation of the
      poly(PHB/PEG urethane)s was monitored using a combination of the physiological
      and accelerated hydrolytic degradation.

PMID- 16305808
TI  - Calcium concentration threshold and translocation kinetics of EGFP-DOC2B
      expressed in cultured Aplysia neurons.
AB  - The double C2 domain protein family (DOC2) is characterized by two calcium
      binding domains (C2). Upon binding to calcium, the affinity of the protein to
      phospholipids is significantly increased, leading to translocation of the protein
      from the cytosol to the plasma membrane. These properties, and the binding domain
      of DOC2B to Munc13, suggested that DOC2B could play a role in augmentation and
      potentiation of synaptic release. Nevertheless, the level of the free
      intracellular calcium concentration ([Ca(2+)](i)) which triggers its
      translocation under in vivo conditions, is not known. Using cultured Aplysia
      neurons that express rat EGFP-DOC2B, we found that the [Ca(2+)](i) increment
      necessary to induce EGFP-DOC2B translocation is approximately 200 nM in the bulk
      of the cytoplasm. The rate of EGFP-DOC2B recruitment to the plasma membrane is
      slower than the [Ca(2+)](i) elevation rate, while the detachment of EGFP-DOC2B
      from it is faster than the calcium removal. The extent of EGFP-DOC2B
      translocation to the plasma membrane reflects local submembrane [Ca(2+)](i). Our
      observations are consistent with the view that DOC2B can participate in the
      regulation of neurotransmitter release. It should be noted that EGFP-DOC2B could
      be used as a tool to map sub-membrane calcium dynamics under physiological
      conditions.

PMID- 16305809
TI  - Peroxisome proliferator-activated receptor gamma as a drug target in the
      pathogenesis of insulin resistance.
AB  - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated
      transcription factors that belong to the nuclear hormone receptor superfamily.
      The activation of PPAR-gamma, an isotype of PPARs, can either increase or
      decrease the transcription of target genes. The genes controlled by this form of
      PPAR have been shown to encode proteins or peptides that participate in the
      pathogenesis of insulin resistance. Insulin resistance is defined as a state of
      reduced responsiveness to normal circulating concentrations of insulin and it
      often co-exists with central obesity, hypertension, dyslipidemia, and
      atherosclerosis. There is substantial evidence that links obesity with insulin
      resistance and type-2 diabetes. The early phase of obesity-related insulin
      resistance has 2 components: (a) interruption of lipid homeostasis leading to the
      increased plasma concentration of fatty acids that is normally suppressed by the
      activation of PPAR-gamma, and (b) activation of factors such as cytokines
      depressed by PPAR-gamma that cause insulin resistance. Therefore, it is logical
      to suggest that activation of PPAR-gamma may partially reverse the state of
      insulin resistance. Evidently, activation of the nuclear receptor, PPAR-gamma, by
      thiazolidinediones has been reported to ameliorate insulin resistance. Although
      hepatotoxity and possibility to induce congestive heart failure (CHF) limit the
      widely use of thiazolodinediones, they are still powerful weapon to fight against
      insulin resistance and type-2 diabetes if use properly. This article reviews the
      physiology of PPAR-gamma and insulin-signaling transduction, the pathogenesis of
      insulin resistance in obesity-related type-2 diabetes, the pharmacological role
      of PPAR-gamma in insulin resistance, and additional effects of
      thiazolidinediones.

PMID- 16305810
TI  - Increased high sensitivity C-reactive protein and neutrophil count are related to
      increased standard cardiovascular risk factors in healthy Chinese men.
AB  - BACKGROUND: Epidemiologic data regarding the role of inflammation in
      atherosclerosis have been based mainly on Caucasian populations. Thus, we
      analyzed the cross-sectional relationships of inflammatory biomarkers to
      cardiovascular risk factors (CVRF) and related variables in a large group of
      healthy Chinese men, a population with a markedly lower heart disease mortality
      rate compared with Western populations. METHODS: The study consisted of 8374 men
      aged 20-80 who attended a voluntary health examination at a metropolitan
      university center between 1997 and 2002. The relationships between serum high
      sensitivity C-reactive protein (hsCRP), total white blood cell (WBC), neutrophil,
      and monocyte counts to CVRF were analyzed using multivariate linear and logistic
      regression analyses. Whether a dose-response effect existed between elevated
      levels of each marker and increasing numbers of CVRF was also evaluated. RESULTS:
      The distribution of hsCRP was similar to Western studies. Both multivariate
      regression analyses showed all four markers to have significant correlations with
      body mass index, triglycerides, and adverse high density lipoprotein/low density
      lipoprotein ratio. Smoking was associated with increased levels of all four
      markers. Elevated neutrophil count had the most markedly progressive dose
      response effect with increasing numbers of CVRF, whereas elevated monocyte count
      showed a drop in risk with CVRF of five and above. CONCLUSION: We show in our
      study that with increasing numbers of standard CVRF, healthy Chinese men have
      progressive and increasing risks of having elevated levels of hsCRP, total WBC,
      and neutrophil counts. While the inflammatory markers surveyed were largely
      correlated with CVRF, the similar values of CRP between populations with
      divergent mortality rates suggest that a more complex relationship may exist
      between CRP and disease outcome. The possible utility of neutrophil count as a
      marker for cardiovascular disease risk in healthy men awaits further evaluation
      in prospective studies.

PMID- 16305811
TI  - DNA extraction from low-biomass carbonate rock: an improved method with reduced
      contamination and the low-biomass contaminant database.
AB  - Caves represent a unique environment in which to study subsurface geomicrobial
      interactions and processes. One of the primary techniques used to study such
      geologic samples is molecular phylogenetic analysis, but this technique is
      hampered by low microbial biomass and calcium in the host rock, often leading to
      poor and irreproducible DNA extraction. We describe an improved protocol to
      recover extremely low amounts of DNA from calcium-rich geologic samples. This
      protocol relies on the use of the synthetic DNA molecule poly-dIdC, to act both
      as blocking agent and carrier molecule to increase the yield of DNA, and dialysis
      to remove calcium inhibitors of PCR amplification. Further, we demonstrate that
      many traditionally used laboratory substrates contain microbial DNA that can be
      amplified through the polymerase chain reaction (PCR) and contaminate molecular
      phylogenetic profiles. While the number of potential contaminants can be
      minimized, it cannot be eliminated from extraction techniques. We have therefore
      established the low-biomass contaminant (LBC) database, which contains the 16S
      rRNA gene sequences of species that have been identified as common laboratory
      contaminants. These identified contaminants provide a reference database to allow
      investigators to critically evaluate certain species identified within their
      phylogenetic profile when examining such low-biomass environments.

PMID- 16305812
TI  - Phosphorylation and dephosphorylation events that regulate viral mRNA
      translation.
AB  - As they are completely dependent upon the protein synthesis machinery resident in
      the cells of their host to translate their mRNAs, it is imperative that viruses
      are able to effectively manipulate the elaborate cellular regulatory network that
      controls translation. Indeed, this exquisite dependence on host functions has
      made viral models attractive systems to explore translational regulatory
      mechanisms operative in eukaryotic cells. Central among these are an intricate
      array of phosphorylation and dephosphorylation events that have far reaching
      consequences on the activity of cellular translation factors. Not only do these
      modulate the activity of a given factor, but they can also determine if the
      translation of host proteins persists in infected cells, the efficiency with
      which viral mRNAs are translated and the outcome of a systemic host anti-viral
      response. In this review, we discuss how various viruses manipulate the
      phosphorylation state of key cellular translation factors, illustrating the
      critical nature these interactions play in virus replication, pathogenesis and
      innate host defense.

PMID- 16305813
TI  - Dendrimers in biomedical applications--reflections on the field.
AB  - The formation of particulate systems with well-defined sizes and shapes is of
      eminent interest in certain medical applications such as drug delivery, gene
      transfection, and imaging. The high level of control possible over the
      architectural design of dendrimers; their size, shape, branching length/density,
      and their surface functionality, clearly distinguishes these structures as unique
      and optimum carriers in those applications. The bioactive agents may be
      encapsulated into the interior of the dendrimers or chemically
      attached/physically adsorbed onto the dendrimer surface, with the option of
      tailoring the carrier to the specific needs of the active material and its
      therapeutic applications. In this regard, the high density of exo-presented
      surface groups allows attachment of targeting groups or functionality that may
      modify the solution behavior or toxicity of dendrimers. Quite remarkably,
      modified dendrimers have been shown to act as nano-drugs against tumors,
      bacteria, and viruses. Recent successes in simplifying and optimizing the
      synthesis of dendrimers such as the 'lego' and 'click' approaches, provide a
      large variety of structures while at the same time reducing the cost of their
      production. The reflections on biomedical applications of dendrimers given in
      this review clearly demonstrate the potential of this new fourth major class of
      polymer architecture and indeed substantiate the high hopes for the future of
      dendrimers.

PMID- 16305815
TI  - Non-attendance and effective equity of access at four public specialist
      outpatient centers in Hong Kong.
AB  - This study tests whether socio-economic status (SES), at either the individual or
      ecologic levels, exerts a direct impact on non-attendance or an indirect impact
      on attendance through longer waiting time for appointments and/or doctor-shopping
      behavior at four public specialist outpatient centers in Hong Kong. We collected
      information through three main sources, namely patients' referral letters,
      telephone interviews with both open- and closed-ended questions (e.g. doctor
      shopping data) and hospital administrative databases from a total of 6495
      attenders and non-attenders enrolled from July 2000 through October 2001.
      Individual-level SES was measured by education, occupation and monthly household
      income. Tertiary planning unit (TPU)-level SES data consisted of proportion
      unemployed, proportion with tertiary education, median income and Gini
      coefficient. Direct effects of SES on non-attendance were examined by logistic
      regression. Indirect contributions mediated through waiting time and doctor
      shopping were analyzed by structural equation modeling. We found that SES, at the
      individual or ecologic level, did not exert a direct effect on non-attendance.
      Instead, TPU-level SES contributed positively to waiting time (beta=0.06+/-0.03,
      p=0.048), i.e. worse-off neighborhoods (and those with greater income inequality)
      had a shorter waiting time. Individual-level SES was also directly associated
      with the likelihood of doctor-shopping (beta=0.16+/-0.02, p<0.001), i.e. the poor
      were less likely to doctor-shop. Both waiting time (beta=0.12+/-0.02, p<0.001)
      and doctor-shopping (beta=0.37+/-0.02, p<0.001) were significantly related to non
      attendance. Our findings suggest a highly equitable specialist ambulatory care
      public system in Hong Kong. Health care resources are appropriately targeted at
      the socially indigent, and the poor are not discriminated against and pushed to
      seek alternative sources of care by the system. These results should be confirmed
      using a prospective design.

PMID- 16305816
TI  - Effects of climate and land use changes on groundwater resources in coastal
      aquifers.
AB  - To estimate the freshwater loss in coastal aquifers due to salinisation, a
      numerical model based on the sharp interface assumption has been introduced. The
      developed methodology will be useful in areas where limited hydrological data are
      available. This model will elaborate on the changes in fresh groundwater loss
      with respect to climate change, land use pattern and hydrologic soil condition.
      The aridity index has been introduced to represent the variations in
      precipitation and temperature. The interesting finding is that the deforestation
      leads to increase groundwater recharge in arid areas, because deforestation leads
      to reduce evapotranspiration even though it favors runoff. The combined climate
      and land use scenarios show that when the aridity index is less than 60, the
      agricultural lands give higher groundwater recharge than other land use patterns
      for all hydrologic soil conditions. The calculated recharge was then used to
      estimate the freshwater-saltwater interface and percentage of freshwater loss due
      to salinity intrusion. We found that in arid areas, the fresh groundwater loss
      increases as the percentage of forest cover increases. The combined effects of
      deforestation and aridity index on fresh groundwater loss show that deforestation
      causes an increase in the recharge and existing fresh groundwater resource in
      areas having low precipitation and high temperature (arid climates).

PMID- 16305817
TI  - Comparative analyses of genomic imprinting and CpG island-methylation in mouse
      Murr1 and human MURR1 loci revealed a putative imprinting control region in mice.
AB  - Human MURR1 is an orthologue of mouse Murr1 gene, which was previously reported
      to be imprinted only in adult brain with a maternal allele-predominant expression
      and to contain another imprinted gene, U2af1-rs1, in the first intron. Human
      MURR1 was found not to harbor the U2af1-rs1 orthologue and to be expressed
      biallelically in tissues, including adult brain. Three genes identified around
      Murr1 and their orthologues around MURR1 were expressed biallelically. These
      findings suggest that the mouse imprinting locus is limited to a small region and
      the introduction of U2af1-rs1 in mouse causes the imprinting of this locus. The
      CpG island (CGI) at U2af1-rs1 with maternal methylation was the only
      differentially methylated region among CGIs found in these loci. Detailed
      methylation analyses of the U2af1-rs1 CGI in germ cells led to identification of
      a region with oocyte-specific methylation. These results suggest that this region
      is the imprinting control region of the Murr1/U2af1-rs1 locus in mouse.

PMID- 16305818
TI  - Neuronal stem cells in adults.
AB  - Neuronal stem cells are like other tissue-specific stem cells, undifferentiated
      cells which can proliferate and may give rise to glia and neurons. They are
      present in mammalians throughout the entire life and are supposed to play an
      important role in renewal of neurons. However, little is known about the origin,
      phenotypic expression and function of neuronal stem cells in the adult brain. In
      the present review the occurrence and origin of neuronal stem cells as well as
      specific markers, which allow their identification in the brain is being
      described. Finally the role of these cells in the adult brain and their potential
      use in neuropathy is discussed.

PMID- 16305819
TI  - Leptin secretion in horses: effects of dexamethasone, gender, and testosterone.
AB  - Five experiments were performed to evaluate the effects of dexamethasone (DEX),
      gender, and testosterone on plasma leptin concentrations in horses. In experiment
      1, plasma leptin, insulin, glucose, and IGF-1 concentrations were increased (P <
      0.01) in stallions following five daily injections of DEX (125 microg/kg BW). In
      experiment 2, leptin concentrations increased (P < 0.01) in mares, geldings, and
      stallions following a single injection of DEX, and the response was greater (P <
      0.01) in mares and geldings than in stallions. The gender effect was confounded
      by differences in body condition scores and diet; however, based on stepwise
      regression analysis, both BCS and gender were significant sources of variation in
      the best fit model for pre-DEX leptin concentrations (R(2) = 0.65) and for
      maximum leptin response to DEX (R(2) = 0.75). In experiment 3, in which mares and
      stallions were pair-matched based on age and body condition and fed similar
      diets, mares again had higher (P < 0.01) leptin concentrations than stallions
      after DEX treatment as used in experiment 2. In experiment 4, there was no
      difference (P > 0.1) in plasma leptin response in mares following four single
      injection doses of DEX from 15.6 to 125 microg/kg BW. In experiment 5, treatment
      of mares with testosterone propionate every other day for 5 days did not alter (P
      > 0.1) plasma leptin concentrations or the leptin response to DEX. In conclusion,
      multiple injections of DEX increase leptin concentrations in stallions, as does a
      single injection in mares (as low as 15.6 microg/kg BW), geldings and stallions.
      The greater leptin levels observed in mares and geldings relative to stallions
      were due partially to their greater body condition and partially to the presence
      of hyperleptinemic individuals; however, even after accounting for body condition
      and diet, mares still had greater leptin concentrations than stallions after DEX
      administration. Elevation of testosterone levels in mares for approximately 10
      days did not alter leptin concentrations in mares.

PMID- 16305820
TI  - Long term morbidity of neoadjuvant chemoradiation for pancreatic head
      adenocarcinoma.
AB  - PURPOSE: To report the long term risks of neoadjuvant chemoradiation (NCRT) after
      duodenopancreatectomy (DP) for adenocarcinoma of the head of pancreas. METHODS:
      Between January 1996 and December 2002, 26 patients with biopsy-proven
      adenocarcinoma of the head of pancreas were treated by this combination of
      therapies. RESULTS: Two patients had delayed NCRT-related small bowel infarction:
      one died from superior mesenteric artery stenosis 36 months after DP without
      recurrence at laparotomy; there was one limited infarction 16 months after DP.
      CONCLUSIONS: Long term vascular morbidity after NCRT is significant.

PMID- 16305821
TI  - The prognosis of patients with local recurrence more than five years after breast
      conservation therapy for invasive breast carcinoma.
AB  - AIMS: The increasing use of breast-conserving therapy (BCT) and the rising
      incidence and improved prognosis of early breast are causing a substantial
      increase in the absolute number of patients with a late local recurrence
      following BCT. This study examined the characteristics and the prognosis of
      patients with a local recurrence occurring more than 5 years after BCT. METHODS:
      In the period 1982-1997, 3280 patients with invasive breast cancer underwent
      breast-conserving therapy in one of the eight community hospitals in the South
      eastern part of The Netherlands. Of these patients, 98 developed a local
      recurrence in the breast more than 5 years after BCT. RESULTS: Eighty-five of the
      98 recurrences were invasive, 12 were purely in situ and for one patient this
      information was not available. The 5 years distant recurrence-free survival rate
      of 85 patients with a late invasive local recurrence was 68% (95% confidence
      interval [CI], 56-80) and significantly better than the rate of 41% (95% CI, 33
      48) in an existing cohort of 173 patients with invasive recurrence within 5 years
      after BCT (p=0.007). Local excision of the recurrence was followed by a
      significantly lower local control rate than salvage mastectomy (50 vs 89%;
      p=0.004). CONCLUSION: The prognosis of patients with a local recurrence more than
      5 years after BCT is significantly better than of patients with local recurrence
      within 5 years after BCT.

PMID- 16305822
TI  - Stimulation of oncogenic metabotropic glutamate receptor 1 in melanoma cells
      activates ERK1/2 via PKCepsilon.
AB  - Metabotropic glutamate receptor 1 (Grm1, formerly mGluR1) is a G protein coupled
      receptor (GPCR) normally expressed and functional in the central nervous system.
      Studies of our transgenic mouse melanoma model (TG-3) revealed that ectopic
      expression of Grm1 in melanocytes is sufficient to induce melanoma development in
      vivo [P.M. Pollock, K. Cohen-Solal, R. Sood, J. Namkoong, J.J. Martino, A.
      Koganti, H. Zhu, C. Robbins, I. Makalowska, S.S. Shin, Y. Marin, K.G. Roberts,
      L.M. Yudt, A. Chen, J. Cheng, A. Incao, H.W. Pinkett, C.L. Graham, K. Dunn, S.M.
      Crespo-Carbone, K.R. Mackason, K.B. Ryan, D. Sinsimer, J. Goydos, K.R. Reuhl, M.
      Eckhaus, P.S. Meltzer, W.J. Pavan, J.M. Trent, S. Chen, Nat. Genet. 34 (2003) 108
      112.]. We have established and characterized several cell lines in vitro from
      independent mouse melanoma tumors [Y.E. Marin, J. Namkoong, S.S. Shin, J. Raines,
      K. Degenhardt, E. White, S. Chen, Neuropharmacol. 49 (2005) 70-79.]. These cell
      lines are useful tools in the studies of signaling events that may be mediated by
      Grm1 in transformed melanocytes. Here we show that stimulation of Grm1 by l
      quisqualate, a group I metabotropic glutamate receptor agonist, results in
      inositol triphosphate (IP3) accumulation, and the activation of ERK1/2 in these
      cell lines. IP3 accumulation and ERK1/2 activation were inhibited by pretreatment
      of the tumor cells with a Grm1-specific antagonist (LY367385) or by dominant
      negative mutants of Grm1, demonstrating the specificity of these events. We also
      show that ERK1/2 activation by Grm1 was PKC-dependent, but cAMP and PKA
      independent. PKCepsilon was shown to play a pivotal role in Grm1-mediated ERK1/2
      phosphorylation. Insights into the signaling cascades mediated by Grm1 in
      melanoma cells may aid in the identification of key molecular targets for the
      future design of combined therapies for melanoma.

PMID- 16305823
TI  - A simple laboratory measurement for discrimination of transudative and exudative
      pleural effusion: pleural viscosity.
AB  - BACKGROUND: The initial step in establishing the cause of an effusion is to
      determine whether the fluid is a transudate or exudate. Plasma viscosity is
      influenced by the concentration of plasma proteins and lipoproteins with the
      major contribution resulting from fibrinogen. In this study we aimed to evaluate
      the role of pleural fluid viscosity in discrimination of transudate and exudates.
      MATERIALS AND METHODS: We studied prospectively 63 consecutive patients with
      pleural effusion in whom diagnostic or therapeutic thoracentesis had been
      performed. The criteria of Light were applied to differentiate transudates from
      exudates: 33 patients (23 male, 13 female, mean age=68+/-4 years) had exudates
      and 30 patients (17 male, 13 female, mean age=68+/-5) had transudates (due to
      congestive heart failure). Measurements of pleural fluid and plasma viscosity
      were performed using a viscometer. RESULTS: There was no statistically
      significant difference between patients with transudate and exudates in respect
      to plasma viscosity. However, pleural viscosities of the patients with exudates
      were significantly higher than those of patients with transudate (1.37+/-0.16 mPa
      vs 0.93+/-0.03 mPa s p<0.001, respectively). Pleural viscosity has a high
      sensitivity, specificity (94%, 93%, respectively), positive and negative
      predictive value (97%, 97%, respectively) for the discrimination of transudative
      or exudatetive pleural fluid. CONCLUSION: We have demonstrated for the first time
      that pleural viscosity of the exudative effusion is higher than that of
      transudative effusion with high sensitivity, specificity, positive and negative
      predictive value. Regarding the simplicity of this measurement, it may play a
      valuable role in the accurate and fast discrimination of pleural fluid.

PMID- 16305824
TI  - Noninvasive arterial measurements of vascular damage in healthy young adults:
      relation to coronary heart disease risk.
AB  - PURPOSE: There is an increasing interest in noninvasive measurements of early
      structural or functional changes in large arteries such as pulse wave velocity
      (PWV), carotid intima-media thickness (CIMT), and augmentation index (AIx). These
      measurements may be applied in etiologic or prognostic research. The role of the
      AIx as a marker of cardiovascular risk has not fully been established. Our aim
      was to study whether AIx is related to coronary heart disease (CHD) risk and to
      compare the strength of the relations of AIx, PWV, and CIMT with cardiovascular
      risk in healthy young adults. METHODS: Our study included 224 men and 273 women
      (mean age 28 years, range 27-30 years) from the Atherosclerosis Risk in Young
      Adults (ARYA) study. Cardiovascular risk profile was determined and CHD risk was
      estimated using the Framingham risk score. AIx, PWV and CIMT were measured using
      standard methods. Data were analyzed in strata of gender using linear regression
      models. RESULTS: In men, PWV and CIMT were most strongly related to CHD risk. The
      increase in CHD risk per standard deviation increase in measurement was
      0.24%/m/s, 95% CI (0.01;0.33) and 0.32%/mm, 95% CI (0.08;0.55), whereas the AIx
      was not significantly related to CHD risk (0.09 %/% 95% CI [-0.15;0.33]). In
      women, AIx, PWV, and CIMT were weakly but significantly related to CHD risk;
      there was no clear difference between the measurements. CONCLUSION: In young men,
      PWV and CIMT are better measures of CHD risk than AIx. In women, AIx, PWV and
      CIMT estimate CHD risk equally well.

PMID- 16305825
TI  - Dependence of amygdala activation on echo time: results from olfactory fMRI
      experiments.
AB  - Echo time dependence of the BOLD sensitivity is an important topic in fMRI
      whenever brain regions are considered where the EPI data quality suffers from
      susceptibility gradients. Here, an fMRI study is presented showing that a reduced
      echo time EPI sequence significantly enhances the statistical inference in
      subcortical (limbic) brain regions, with special focus on the amygdala. As a
      consequence, to facilitate whole-brain fMRI with optimal echo times, a sequence
      with slice-dependent echo time is demonstrated with a focus on structures
      suffering from susceptibility changes. The applicability of this method is shown
      in a second fMRI study aimed at both, cortical, and limbic brain regions. The
      results are in good agreement with theoretical descriptions of the BOLD
      sensitivity under the influence of susceptibility gradients.

PMID- 16305826
TI  - Accuracy of B-type natriuretic peptide levels in the diagnosis of left
      ventricular dysfunction and heart failure: a systematic review.
AB  - OBJECTIVES: To evaluate the accuracy of B-type natriuretic peptide levels (BNP)
      in the diagnosis of heart failure and left ventricular dysfunction. DATA SOURCES:
      Electronic search in Medline, Embase, Cochrane Library and Medion database, and
      hand search of reference lists. REVIEW METHODS: We have included published
      studies on the accuracy of BNP which had both sufficient information to construct
      the 2x2 diagnostic cross table and an appropriate spectrum of patients. RESULTS:
      Fifty five studies (16,730 patients) were analyzed. The main determinants of
      diagnostic accuracy were the reference standard analyzed (clinical heart failure
      versus left ventricular dysfunction), and the methodological quality of the
      study. BNP levels were highly accurate for the diagnosis of clinical heart
      failure (diagnostic OR=41; 95% CI 23-74). The negative likelihood ratios were
      homogeneous, and useful for excluding the existence of heart failure (pooled
      negative likelihood ratio=0.11; 95% CI 0.08-0.16). The studies focused on the
      identification of left ventricular dysfunction were heterogeneous, with
      indications of publication bias, and showed less overall diagnostic accuracy than
      studies focused on heart failure. CONCLUSIONS: BNP levels are useful for ruling
      out heart failure. The accuracy of BNP for identifying patients with systolic
      dysfunction is more limited.

PMID- 16305827
TI  - Expression of the neurokinin type 1 receptor in the human colon.
AB  - The distribution of the neurokinin type 1 receptor (NK1r) in human intestine,
      mapped in a few immunohistochemical investigations in the antrum and the
      duodenum, is comparable to that widely studied in rodents. Importantly, despite
      pharmacological evidence of their presence in mammalian intestinal muscle, their
      immunohistochemical visualization in smooth muscle cells remains to be determined
      in human digestive tract. In the present work, we studied the distribution of
      NK1r in the human colon, with a particular view to visualize their expression in
      muscle cells. With this aim, part of colonic segments were incubated with
      nicardipine and TTX in order to induce accumulation of the NK1r on cell membrane.
      NK1r were visualized by using immunohistochemistry combined with fluorescence and
      confocal microscopy. Without incubation, NK1r-IR was clearly observed on the
      membrane and the cytoplasm of myenteric and submucous neurons and interstitial
      cells of Cajal, but could not be clearly determined in the longitudinal and
      circular muscle. NK1r-IR-expressing neurons and interstitial cells were closely
      surrounded by substance P (SP) immunoreactive nerves. Incubation of colonic
      segments with nicardipine and TTX at 4 degrees C for 1 h with SP allowed to
      reveal a strong NK1r-IR at the surface of muscle cells. Incubation with SP (10(
      6) M) at 37 degrees C for 1 min induced a relocation of NK1r-IR into the
      cytoplasm of muscle. This is interpreted as an internalization of NK1r induced by
      the binding of SP on muscular NK1r. The present data contribute to emphasize the
      role of NK1r in tachykinin-mediated neuronal processes regulating intestinal
      motility.

PMID- 16305829
TI  - Home schooling.

PMID- 16305828
TI  - Hemoglobin/colloidal silver nanoparticles immobilized in titania sol-gel film on
      glassy carbon electrode: direct electrochemistry and electrocatalysis.
AB  - By vapor deposition method, both hemoglobin (Hb) and colloidal silver
      nanoparticles (CSNs) were entrapped in a titania sol-gel matrix on the surface of
      a glassy carbon electrode (GCE). CSNs could greatly enhance the electron transfer
      reactivity of Hb and its catalytic ability toward nitrite. Direct fast electron
      transfer between Hb and the GCE was achieved, and a pair of well-defined, quasi
      reversible redox peaks was observed. The anodic and cathodic peak potentials are
      located at -0.298 V and -0.364 V (vs. Ag/AgCl), respectively. The dependence of
      the formal potential on solution pH indicated that the direct electron transfer
      reaction of Hb was a one-electron transfer coupled with a one-proton transfer
      reaction process. Meanwhile, the catalytic ability of Hb toward the reduction of
      NO2- was also studied. Accordingly, a NO2- biosensor was prepared, with a linear
      range from 0.2 mM to 6.0 mM and a detection limit of 34.0 microM. The apparent
      Michaelis-Menten constant was calculated to be 7.48 mM. Moreover, the biosensor
      had good long-term stability.

PMID- 16305830
TI  - Extended surgical staging for potentially resectable malignant pleural
      mesothelioma.
AB  - BACKGROUND: Extrapleural pneumonectomy for malignant pleural mesothelioma (MPM)
      is a high-risk procedure, and patients require careful preoperative staging to
      exclude advanced disease. Computed tomography, magnetic resonance imaging, and
      positron emission tomography are useful staging modalities, but do not reliably
      identify contralateral mediastinal involvement or transdiaphragmatic invasion. We
      evaluated the role of extended surgical staging procedures, which generally
      includes a combination of laparoscopy, peritoneal lavage, and mediastinoscopy, to
      more precisely stage patients with MPM. METHODS: One hundred eighteen patients
      with MPM, deemed clinically and radiologically resectable, underwent extended
      surgical staging. Mediastinoscopy was performed in 111 patients, laparoscopy in
      109 patients, and peritoneal lavage in 78 patients. RESULTS: Ten (9.2%) patients
      had gross evidence of transdiaphragmatic or peritoneal involvement. Peritoneal
      lavage was positive for metastatic MPM in 2 (2.6%) patients, neither of whom had
      obvious transdiaphragmatic invasion. Ipsilateral mediastinal nodes contained
      metastatic tumor in 10 of 62 (16.1%) patients. Contralateral nodes were positive
      in 4 of 111 (3.6%) patients. Of the patients who underwent biopsy of both
      ipsilateral and contralateral mediastinal nodes, and who had complete pathologic
      staging after extrapleural pneumonectomy (n = 46), 14 (30.4%) had N2-positive
      nodes. Only 5 of these patients were correctly identified by mediastinoscopy
      (sensitivity 36%, accuracy 80%). Extended surgical staging identified 16 (13.6%)
      patients who had contralateral nodal involvement, transdiaphragmatic invasion, or
      positive peritoneal cytology. CONCLUSIONS: Extended surgical staging defines an
      important subset of patients with unresectable MPM not identified by imaging.
      Because of the potential morbidity associated with extrapleural pneumonectomy, we
      advocate that extended surgical staging be performed in all patients with MPM
      before resection.

PMID- 16305831
TI  - Proposal of a novel system for the staging of thymic epithelial tumors.
AB  - BACKGROUND: We designed and assessed a new TNM staging system (herein called the
      INT [Istituto Nazionale Tumori] system) for thymic epithelial tumors in order to
      overcome the perceived drawbacks of Masaoka's system, which represents the
      current standard. METHODS: In all, 123 cases were evaluated. The histologic types
      according to the World Health Organization (WHO) classification were as follows:
      subtype A: 5 cases; AB: 40; B1: 16; B2: 29; B3: 16; and C: 17 cases. There were
      45 Masaoka's stage I, 33 stage II, 26 stage III, and 19 stage IV cases. A total
      of 11 INT definitions were grouped into three stages: locally restricted disease
      (75 cases), which included Masaoka's stage I and selected stage II cases (no
      pleural invasion); locally advanced disease (37 cases), which included Masaoka's
      stage III cases plus those staged II owing to pleural invasion and those staged
      IV owing to intrathoracic nodal or limited pleuropericardial involvement; and
      systemic disease (11 cases), which included the remaining Masaoka's stage IV
      cases. RESULTS: Completeness of resection, WHO types, and both staging systems
      were significant prognostic factors (p < 0.0001) on univariate analysis. The 95
      month progression-free survival rates according to Masaoka's system were stage I:
      100%; II: 93.6%; III: 46.3%; and IV: 23.2%. The INT system corresponding figures
      were as follows: locally restricted disease: 98.6%; locally advanced disease:
      46.9%; and systemic disease: 11.7%. The INT system was the prognostic factor with
      the greatest impact (p = 0.0218) on multivariate analysis (Masaoka's system: p =
      0.2012; completeness of resection: p = 0.6855; histology: p = 0.9386).
      CONCLUSIONS: The INT system allows finer disease descriptions than Masaoka's
      system, resulting in a stage grouping with higher prognostic distinctiveness.

PMID- 16305832
TI  - Invited commentary.

PMID- 16305833
TI  - Surgical management of thymic epithelial tumors: a retrospective review of 204
      cases.
AB  - BACKGROUND: Thymic epithelial tumors consist of a series of neoplasm that differ
      morphologically and biologically. Management strategy for these tumors remains
      controversial. METHODS: We retrospectively reviewed 204 thymic epithelial tumors
      surgically treated during the period of 1970 to 1995, and we reexamined the
      histologic specimens using the current World Health Organization classification.
      RESULTS: One hundred eighty patients (88.2%) underwent complete resections, 17
      (8.3%) received partial resections, and 7 (3.4%) received biopsies only. The
      complete resection rate of stages I and II tumors was significantly higher than
      stages III and IV tumors (98.2% vs 76.6%; p < 0.001). Twenty-four patients
      (11.8%) experienced 29 events of complications postoperatively, including 11
      events of myasthenia gravis crisis. Myasthenia gravis, partial resection or
      biopsy, and stages III and IV were independent risk factors for postoperative
      complications. Fifteen patients (7.4%) died during hospital stays, including 6
      patients from myasthenia crisis. Partial resection or biopsy and myasthenia
      gravis were independent risk factors for postoperative mortality. There were
      significantly more stage I and stage II cases in histologic types A, AB, and B1
      tumors than in B2, B3, and C tumors (87.6% vs 26.4%; p < 0.001), and their
      complete resection rate was significantly higher than the latter group (98.9% vs
      78.3%; p < 0.001). The 5-year and 10-year survival rates were 63.2% and 50.4%,
      respectively. Masaoka stages III and IV, histologic types B2, B3, and C, and
      incomplete resection were independent risk factors for poor prognosis.
      CONCLUSIONS: Complete resection remains the hope of cure for thymic epithelial
      tumors. The treatment strategy should be based on the current World Health
      Organization histologic classification and the Masaoka staging system.

PMID- 16305834
TI  - Invited commentary.

PMID- 16305835
TI  - Late-onset occult pneumothorax after lung volume-reduction surgery.
AB  - BACKGROUND: Lung volume-reduction surgery has proved to be a reliable palliative
      surgical treatment for patients with severe emphysema. Nonetheless, late
      complications can arise after lung volume-reduction surgery although this matter
      has been poorly investigated by previous studies. METHODS: We report a series of
      6 patients undergoing unilateral lung volume-reduction surgery at our institution
      between October 1995 and December 2004, who were readmitted several months after
      discharge because of the occurrence of occult pneumothorax mimicking acute
      respiratory failure. RESULTS: Occult pneumothorax occurred in 3.3% of the 182
      patients treated with lung volume-reduction surgery at our institution. Patients
      were readmitted after a mean of 94 days (range, 20 to 700 days) from the
      discharge. Chest roentgenography was unable to detect the occurrence of
      pneumothorax, which was instead revealed by means of a computed tomographic scan
      in all patients. The interval between admission and correct diagnosis averaged
      22.4 hours. The number of air collections ranged between two and four. Treatment
      entailed solely blind chest drainage placement in 2 patients and awake video
      assisted thoracoscopic surgery in the others, including placement of chest tube
      under direct vision in 1 patient, repair of lung tears by means of cyanoacrylate
      glue in 2 and bovine pericardium patch plus cyanoacrylate glue apposition in 1
      patient. CONCLUSIONS: In conclusion, we believe that occult pneumothorax should
      be kept in mind as one of the possible late complications of lung volume
      reduction surgery and should be suspected whenever sudden worsening of dyspnea is
      noticed even in the presence of an uneventful chest roentgenogram. Awake video
      assisted thoracoscopic surgery management can represent an effective option in
      these instances.

PMID- 16305836
TI  - Comparative study of subxiphoid versus video-thoracoscopic pericardial "window".
AB  - BACKGROUND: It remains undefined whether surgical subxiphoid drainage or
      thoracoscopic pericardial "window" is the optimal operative approach to
      pericardial effusion. We hypothesized that the true window into the pleural space
      created by the latter might improve the duration of freedom from recurrent
      effusion. METHODS: We conducted a retrospective chart review of indications,
      preoperative and intraoperative variables, morbidity, recurrence, and survival.
      RESULTS: Fifty-six patients underwent the subxiphoid procedure and 15 underwent
      the thoracoscopic procedure. Echocardiographic evidence of tamponade was present
      before 8 of 10 thoracoscopic procedures (80%) and 43 of 56 subxiphoid procedures
      (81%) for which descriptions of hemodynamics were available. In addition, non
      pericardial procedures were performed in 10 (67%) and 18 (32%) patients,
      respectively (p = 0.020). Anesthesia time was longer at thoracoscopy (117.1 +/-
      32.4 vs 81.1 +/- 25.5 minutes; p < 0.001). Procedural morbidity was higher after
      thoracoscopy (4 [27%] vs 1 [2%]; p = 0.006), but was generally minor. Hospital
      mortality tended to be higher after the subxiphoid procedure (7 [13%] vs 0 [0%];
      p = 0.332), but none of the deaths was procedure-related. Follow-up was complete
      for 65 patients (92%). Recurrence occurred in 1 thoracoscopy patient (8%) and 5
      subxiphoid patients (10%) (p = 1.000). Mean time to recurrence by Kaplan-Meier
      analysis trends were longer after thoracoscopy (36.1 vs 11.4 months; p = 0.16),
      and multivariate analysis identified the thoracoscopic approach as an independent
      predictor of freedom from recurrence (relative risk, 0.41; p = 0.014).
      CONCLUSIONS: Operative time and minor procedural morbidity are higher with
      thoracoscopic pericardial window, but long-term control of effusion seemed to be
      better than after subxiphoid surgical drainage.

PMID- 16305837
TI  - 11C-acetate positron emission tomography imaging for lung adenocarcinoma 1 to 3
      cm in size with ground-glass opacity images on computed tomography.
AB  - BACKGROUND: Positron-emission tomography (PET) with 18F-fluorodeoxy-glucose (FDG)
      frequently gives false-negative results for well-differentiated adenocarcinomas
      of the lung, especially, those with ground-glass opacity images. Recently, PET
      with 11C-acetate (AC) has been reported to detect slow-growing tumors that have
      failed to be identified by FDG-PET, such as well-differentiated hepatocellular
      carcinomas and prostate cancers. To determine the usefulness of AC-PET in
      detecting well-differentiated adenocarcinomas of the lung, we performed both AC
      PET and FDG-PET on pulmonary nodules with ground-glass opacity images on computed
      tomography (CT). METHODS: Fifty-four pulmonary nodules 1 to 3 cm in size, which
      showed ground-glass opacity images over their whole or peripheral area on CT,
      were examined by both AC-PET and FDG-PET. RESULTS: Thirty-seven nodules were
      adenocarcinoma of the lung, while 17 were inflammatory. Of the 37
      adenocarcinomas, 19 (51%) were positively identified by AC-PET and 14 (38%) by
      FDG-PET. Of the 23 adenocarcinomas which were not identified by FDG-PET, 8 (35%)
      were positively identified by AC-PET; all were well-differentiated
      adenocarcinomas. Of the 17 inflammatory nodules, 8 were chronic and 9 were acute
      ones. While none of the 8 chronic inflammatory nodules were identified by either
      technique, 9 acute ones showed a variety of the results with AC- and FDG-PET.
      CONCLUSIONS: AC-PET detected approximately one third of well-differentiated
      adenocarcinomas of the lung which were not identified by FDG-PET. AC-PET could be
      useful to diagnose pulmonary nodules with ground-glass opacity images which were
      not identified by FDG-PET.

PMID- 16305838
TI  - Risk of pleural recurrence after needle biopsy in patients with resected early
      stage lung cancer.
AB  - BACKGROUND: Concerning the complications resulting from percutaneous needle
      biopsy (PNB), although cases of tumor seeding into the needle track have
      occasionally been reported, there were only two cases of pleural recurrences to
      date. The aim of this study was to elucidate the real risk of pleural recurrence
      after needle biopsy in patients with resected early stage lung cancer. METHODS:
      Between 1986 and 2000, 335 patients with stage I nonsmall cell lung cancer
      underwent complete resection of the lung tumor. We retrospectively reviewed their
      medical records and investigated the relationship between the diagnostic methods
      used and the cancer recurrence patterns. RESULTS: Preoperative diagnoses were
      obtained for 290 patients; 220 were diagnosed by bronchoscopy and 66 by PNB.
      Among the patients without a preoperative diagnosis, 27 were diagnosed by
      intraoperative needle biopsy and 14 by wedge resection of the lung. Tumors
      diagnosed by needle biopsy including PNB and intraoperative needle biopsy were
      smaller and showed less vessel invasion than those diagnosed by other methods (p
      < 0.01). After surgical resection, 9 patients had pleural recurrence and 1
      patient, needle track implantation. Seven of these 10 patients were diagnosed by
      needle biopsy using 18G cutting type needle. Pleural recurrence or needle track
      implantation was observed for 8.6% of the patients who underwent a needle biopsy,
      whereas it was 0.9% for patients who were examined using other diagnostic
      modalities (p = 0.0009). CONCLUSIONS: Needle biopsy especially using a cutting
      type biopsy needle can cause a pleural recurrence in addition to needle track
      implantation.

PMID- 16305839
TI  - Lung cancer invading the chest wall: a plea for en-bloc resection but the need
      for new treatment strategies.
AB  - BACKGROUND: Factors influencing survival of patients with a nonsmall-cell lung
      cancer (NSCLC) invading the parietal pleura or the chest wall are still
      controversial. The aim of this study was to assess prognostic factors in
      completely resected pT3 chest wall NSCLC patients. METHODS: We retrospectively
      reviewed a three-center experience between 1984 and 2002 with 309 patients.
      RESULTS: There were 269 male and 40 female patients. Pulmonary resections
      consisted of 13 wedge resections or segmentectomies, 211 lobectomies, 6
      bilobectomies, and 79 pneumonectomies. One hundred patients underwent
      extrapleural mobilization, and 209, en-bloc resection. Tumors were staged as
      stages IIB (n = 212) and IIIA (n = 97). Overall 5-year survival rates were 40%
      and 12% for stage IIB and IIIA, respectively (p < 10(4)). Multivariate analysis
      shows male sex and bigger tumor size as independent indicators of poor prognosis
      in stage IIB patients. In stage IIB patients with a chest wall invasion limited
      to the parietal pleura, en-bloc resections provided higher 5-year survival rates
      when compared with extrapleural resections (60.3% versus 39.1%; p = 0.03). In
      stage IIIA patients, multivariate analysis disclosed two independent prognostic
      factors: the number of resected ribs and adjuvant parietal and mediastinal
      radiotherapy. CONCLUSIONS: The presence of lymph node metastases has a disastrous
      impact on survival in this subset of patients. En-bloc resection is strongly
      suggested to be the standard of surgical care, and adjuvant radiotherapy does not
      seem to be necessary in N0 patients when a complete R0 resection has been
      achieved. For huge tumors (larger than 6 cm), this report suggests that the role
      of perioperative chemotherapy needs further evaluation.

PMID- 16305840
TI  - Invited commentary.

PMID- 16305841
TI  - Functional advantage after radical segmentectomy versus lobectomy for lung
      cancer.
AB  - BACKGROUND: Although several reports have recently demonstrated that
      segmentectomy for small-sized N0 lung cancer leads to recurrence and survival
      rates equivalent to those associated with lobectomy, controversy regarding the
      postoperative functional advantage in the former over the latter still persists.
      The purpose of this study was to evaluate the degree of postoperative functional
      loss in patients undergoing segmentectomy or lobectomy for lung cancer. METHODS:
      We analyzed patients able to tolerate lobectomy, who underwent radical
      segmentectomy (n = 38) or lobectomy (n = 45) for non-small-cell lung cancer.
      Functional testing included forced vital capacity, forced expiratory volume in 1
      second, and anaerobic threshold measured preoperatively and at 2 and 6 months
      after surgery. RESULTS: Preoperative function tests showed no differences between
      segmentectomy and lobectomy patients. A positive and significant correlation was
      found between the number of resected segments versus loss of forced vital
      capacity (r = 0.518, p < 0.0001 at 2 months; r = 0.604, p < 0.0001 at 6 months)
      and loss of forced expiratory volume in 1 second (r = 0.492, p < 0.0001 at 2
      months; r = 0.512, p < 0.0001 at 6 months). The postoperative reduction of forced
      vital capacity (p = 0.0006) and forced expiratory volume in 1 second (p = 0.0007)
      was significantly less in the segmentectomy group; however, a marginally
      significant benefit was observed in this group for anaerobic threshold (p =
      0.0616). CONCLUSIONS: The extent of removed lung parenchyma directly affected
      that of postoperative functional loss even at 6 months after surgery, and
      segmentectomy offered significantly better functional preservation compared with
      lobectomy. These results indicate the importance of segmentectomy for early
      staged lung cancer.

PMID- 16305842
TI  - Sleeve lobectomy versus pneumonectomy: tumor characteristics and comparative
      analysis of feasibility and results.
AB  - BACKGROUND: Sleeve lobectomy (SL) seems to have better results than
      pneumonectomy. Some authors propose to extend its indications. The aim of this
      study was to compare postoperative results, locoregional recurrence, and survival
      after sleeve lobectomy and pneumonectomy in focusing on right upper lobe cancer.
      METHODS: From 1984 to 2002, 973 lung resections were performed for T1, T2, and
      bronchial T3 right upper lobe non-small cell lung cancer. There were 756
      lobectomies (L group), 151 pneumonectomies (RP group), and 66 sleeve lobectomies
      (SL group). The RP group was further divided with regard to intrapulmonary lymph
      node involvement. Pneumonectomy 1 (RP1) was a group of N0, intralobar N1, and
      skip metastasis involvement (N0-N2). Pneumonectomy 2 (RP2) was a group of
      extralobar N1 and nonskip metastasis involvement (N1-N2). Postoperative results
      were compared among SL, L, and RP groups. Survival was compared between the two
      homogeneous groups for oncologic characteristics (SL, RP1). RESULTS: Statistical
      comparison of 5-year actuarial survival showed a significant difference favoring
      SL (SL: 72.5%/ RP1: 53.2%; p = 0.0025). Postoperative mortality was higher after
      RP (L: 2.9% / SL: 4.5%/ RP: 12.6 %). Significant factors limiting SL were tumor
      size, extralobar N1, and main bronchus involvement (p = 0.000026, 0.0002, and
      0.005, respectively). CONCLUSIONS: Immediate and long-term survival appears
      better after sleeve lobectomy than right pneumonectomy for comparable stages of
      right upper lobe cancer. For frequency to increase by systematic attempt at SL,
      limited by large tumors and extralobar N1 involvement, the only way should be
      after favorable response to induction chemotherapy.

PMID- 16305843
TI  - Patterns of surgical care of lung cancer patients.
AB  - BACKGROUND: This survey was performed to determine the patterns of surgical care
      provided patients with non-small cell lung carcinoma (NSCLC). METHODS: In 2001,
      the American College of Surgeons carried out a patient care survey of 729
      hospitals to retrieve information of NSCLC patients' history, evaluation,
      pathology, and surgical treatment. RESULTS: Inclusion criteria were met by 40,090
      patients: of whom 11,668 (29.1%) were treated surgically; 74.2% alone and 25.8%
      as part of multimodality therapy. Of these patients, 59.5% were in stage I, 17.5%
      in stage II, 17.0% in stage III, and 6.0% in stage IV. Surgery patient
      demographics were the following: 55% male and 45% female; 46.8% 70 years or
      older; and 76.3% had significant comorbidities. Tumor characteristics: squamous
      28%, adenocarcinoma 37.6%, other 34.4%. Staging: in addition to radiologic
      examinations, preoperative mediastinoscopy was performed in 27.1% of operated
      patients with node biopsy in only 46.6% of these procedures. OPERATIONS: wedge
      resection 15.6%, lobectomy 70.8%, pneumonectomy 13.6%. Surgical margins were
      positive in 7.8%, but only 65.2% had frozen section analysis. Perioperative
      mortality was 5.2%, but was 4.0% in nontransfused patients and 12.7% in
      transfused patients and was 3.2% in high-volume (more than 90 operations per
      year) versus 4.8% in low-volume hospitals (p < 0.001). CONCLUSIONS: (1) Patients
      being operated for NSCLC are elderly with significant comorbid conditions. (2)
      More patients than previously are female and have adenocarcinoma. (3)
      Mediastinoscopy is infrequently performed and lymph nodes are biopsied in less
      than 50% of them. (4) Lobectomy is the most common operation, and positive
      surgical margins are too frequent. (5) Operative mortality is reasonable but
      transfusion is a marker for increased risk and outcomes are superior in high
      volume hospitals. (6) Hospitals with higher volume had fewer perioperative
      deaths.

PMID- 16305844
TI  - Tracheal compression caused by straight back syndrome, chest wall deformity, and
      anterior spinal displacement: techniques for relief.
AB  - BACKGROUND: Straight back syndrome and other causes of extreme narrowing of the
      space between sternal notch and vertebrae can cause critical tracheal
      obstruction. Additional points of compression may result from the brachiocephalic
      artery and from anterior vertebral displacement. METHODS: Individualized surgical
      maneuvers are necessary to correct all points of obstruction. Techniques include
      sternoplasty, sternal division, reimplantation of brachiocephalic artery,
      correction of severe pectus excavatum, and posterior wall tracheoplasty. RESULTS:
      Four patients were successfully treated by individualized techniques with
      complete long-term relief of critical tracheal obstruction. CONCLUSIONS: Severe
      tracheal compression caused by straight back syndrome and other causes of
      narrowed sternospinal channel is surgically correctable.

PMID- 16305845
TI  - Reconstitution of blood supply of the denuded bronchial stump.
AB  - BACKGROUND: Our aim was to study the process of microcirculatory reconstitution
      in the bronchial stump after pneumonectomy. METHODS: Eighteen juvenile pigs
      (median weight 40.6 kg) were randomly assigned to three groups. In all animals
      left pneumonectomy was performed and the stapled bronchial stump (median length
      3.8 cm) carefully denuded. Group I animals received coverage of the stump by
      intercostal flap. In group II, the stump was covered with TachoComb, an
      impermeable hemostatic fleece; and group III served as a control without any
      coverage of the stump. Animals were sacrificed at day 14 after surgery. Vascular
      density was evaluated in serial histologic sections at multiple levels stained
      with CD-31 antibody. One-way analysis of variance and the Wilcoxon test were used
      for data analysis. RESULTS: At autopsy, stumps of group III animals were totally
      covered by adjacent mediastinal structures. In group I, intercostal flaps were
      viable and completely healed to the bronchial stumps. There were no signs of
      infection or stump insufficiency in these groups. In all group II animals,
      empyema developed, and stumps were found necrotic at macroscopic and histologic
      evaluation. Statistical analysis revealed significantly lower vascular density of
      mature vessels in the area of the bronchial stump in group II compared with both
      other groups. CONCLUSIONS: Reconstitution of microcirculation of the denuded
      bronchial stump after pneumonectomy takes place in a centripetal way from
      adjacent viable tissue. Hence, the purpose of covering the bronchial stump is the
      improvement of blood supply rather than mechanical reinforcement.

PMID- 16305846
TI  - Minimally invasive esophagectomy for stage I and II esophageal cancer.
AB  - BACKGROUND: To evaluate whether thoracoscopic and video-assisted dissections are
      appropriate modalities, we assessed the mortality, morbidity, and survival of
      patients who underwent a thoracoscopic esophagectomy for esophageal cancer.
      METHODS: Between November 1995 and December 2004, thoracoscopic and video
      assisted esophagectomies were performed on 112 (72.7%) patients out of 154 who
      underwent surgical resection for thoracic and abdominal esophageal cancer. The
      histologic type of cancer was squamous cell carcinoma in 109 (97.4%) patients and
      adenocarcinoma in 3 (2.6%). RESULTS: Intraoperative complications occurred in 4
      (3.6%) patients: tracheal injury in 3 (2.7%) and azygos vein injury in 1 (0.8%).
      The 30-day mortality rate was 0.8%. Early postoperative complications occurred in
      29 (25.9%) patients including the following: recurrent nerve palsy in 10 (8.9%),
      respiratory complication in 7 (6.3%), anastomotic leakage in 9 (8.0%) with major
      leakage requiring reanastomosis in 4 (3.6%) of these 9, and chylothorax in 3
      (2.7%). Induction chemoradiotherapy, preoperative concomitant disease, and
      reconstruction using the colon did not increase morbidity. Port site recurrence
      occurred in 3 (2.7%) patients. The overall 5-year survival rate was 52%. For
      stage I disease, the 5-year survival rate of patients was 87.2%. In stage II
      disease, it was 70.2%. CONCLUSIONS: Thoracoscopic and video-assisted
      esophagectomy are considered feasible and safe options for the treatment of
      esophageal cancer, but further investigation is necessary. The survival of
      patients with stage I and II disease is satisfactory at the present time.

PMID- 16305847
TI  - Minimally invasive operation for esophageal diverticula.
AB  - BACKGROUND: Mid and lower esophageal diverticula are rare entities usually
      managed by open operation. Morbidity can be significant with these complex
      procedures. This study evaluates our results of minimally invasive surgery for
      esophageal diverticula. METHODS: Over a 5-year period, 20 patients underwent
      operation for esophageal diverticula. Median age was 70.5 years. There were 16
      epiphrenic and 4 midesophageal diverticula with a median size of 7.5 cm (range, 2
      11 cm). Symptoms included dysphagia (14), regurgitation (12), weight loss (8),
      heartburn (4), aspiration pneumonia (3), chest pain (2), and vomiting (2).
      Dysphagia scores (1 = none, 5 = severe) were recorded before and after operation.
      RESULTS: Surgical approaches were laparoscopy (10), video-assisted thoracic
      surgery (VATS) (7), laparoscopic/VATS (2), and laparoscopic/thoracotomy (1). The
      most common operation performed was a diverticulectomy, myotomy, and partial
      fundoplication (12). Complications occurred in 9 (45%) patients and included 4
      (20%) esophageal leaks. Three leak patients had successful outcomes; the fourth
      patient died 61 days after operation. Median hospital stay was 5.0 (1-61) days.
      Detailed follow-up was available in 18 patients at a median of 15 (1-70) months.
      Dysphagia scores improved significantly (p < 0.001) from 2.3 to 1.3
      postoperatively. Symptomatic improvement was excellent in 13 (72%), good in 2
      (11%), fair in 1 (6%), and poor in 2 (11%) patients. CONCLUSIONS: Minimally
      invasive operations for esophageal diverticula are feasible but also challenging.
      The potential for morbidity is significant. Patients should be selected and
      evaluated carefully before undertaking repair. Open surgery should remain the
      standard except in centers experienced with minimally invasive esophageal
      surgery.

PMID- 16305848
TI  - Invited commentary.

PMID- 16305849
TI  - Impact of unstable angina on outcomes of transmyocardial laser revascularization
      combined with coronary artery bypass grafting.
AB  - BACKGROUND: For sole therapy transmyocardial laser revascularization (TMR),
      unstable angina has been demonstrated to be a significant independent predictor
      of operative mortality. The objective of this study was to investigate the
      preoperative risk profile of patients undergoing TMR plus coronary artery bypass
      graft surgery (CABG) and to determine the impact of unstable angina on outcomes.
      METHODS: Using The Society of Thoracic Surgeons National Cardiac Database from
      1998 to 2003, 5,618 patients underwent TMR plus CABG. These patients were
      compared with 932,715 patients who underwent CABG only operations. RESULTS: The
      TMR plus CABG patients had a significantly higher incidence of diabetes (50%
      versus 34%), renal failure (7% versus 5%), peripheral vascular disease (20%
      versus 16%), reoperative surgery (26% versus 9%), three-vessel coronary artery
      disease (80% versus 71%), hyperlipidemia (73% versus 62%; p < 0.001 for all
      comparisons). The incidence of preoperative unstable angina was similar (46%
      versus 47%). The unadjusted perioperative mortality was 3.8% for TMR plus CABG
      patients. When unstable angina patients were removed, the observed mortality for
      TMR plus CABG was decreased to 2.7%. CONCLUSIONS: It is likely that patients who
      undergo TMR plus CABG have a higher prevalence of diffuse coronary disease based
      on their preoperative demographics. Despite the increased risk associated with
      such anatomy, the mortality rate was not significantly increased when TMR was
      added to CABG in an effort to provide a more complete revascularization. As was
      noted from the outcomes of sole therapy TMR, in unstable angina patients, TMR
      plus CABG carries a higher risk, but this risk is not significantly different
      from that of such patients treated with CABG alone.

PMID- 16305850
TI  - Drug-eluting stents versus bilateral internal thoracic grafting for multivessel
      coronary disease.
AB  - BACKGROUND: Reduction of restenosis and reinterventions was recently reported
      with percutaneous interventions (PCI), including drug-eluting stents (Cypher;
      Cordis, Miami Lakes, FL). This study compares results of multivessel Cypher
      stenting with those of bilateral internal thoracic artery (BITA) grafting.
      METHODS: From January 2002 to June 2004, 768 consecutive patients underwent
      multivessel myocardial revascularization; 138 by PCI including Cyphers and 630 by
      BITA. After matching for age, sex, ejection fraction, extent of coronary disease,
      and congestive heart failure, two groups (113 patients each) were used to compare
      the two revascularization modalities. RESULTS: Both groups were similar; however,
      left main and intraaortic balloon were more prevalent in the BITA group. The
      number of coronary vessels treated per patient was higher in the BITA group (2.87
      vs 2.22, p < 0.001). Follow-up ranged between 6 and 34 months. Thirty-day
      mortality was 0.9% in the BITA and zero in the PCI group (p = 0.32). There were
      no late deaths in the BITA and three (2.7%) in the Cypher group (p = 0.08).
      Angina returned in 28.3% of the Cypher and 12.4% of the BITA group, p = 0.003. A
      Cox proportional hazard model revealed assignment to the Cypher group to be the
      only predictor of angina recurrence (odds ratio 2.78, 95% confidence interval
      1.46-2.56). There were 16 (14.2%) reinterventions in the Cypher group compared
      with six (5.3%) in the BITA group. One-year reintervention-free survival (Kaplan
      Meier) of the BITA was 96% compared with 86.6% in the Cypher group (p = 0.005,
      log-rank test). CONCLUSIONS: Despite improved results of PCI with Cyphers,
      midterm clinical outcome of multivessel patients treated with BITA is still
      better.

PMID- 16305851
TI  - Late results of combined carotid and coronary surgery using actual versus
      actuarial methodology.
AB  - BACKGROUND: Controversy exists over the short-term results and long-term efficacy
      of concomitant coronary artery bypass grafting and carotid endarterectomy.
      Additionally, in this population actual versus actuarial assessment of nonfatal
      late events has not been previously reported. METHODS: Hospital records of 500
      consecutive patients having concomitant carotid endarterectomy and coronary
      artery bypass grafting between 1979 and 2001 were reviewed, allowing at least 1
      year of follow-up on all patients. Long-term nonfatal complications were assessed
      by actual and actuarial methods. RESULTS: Patient demographics revealed a mean
      age of 69 years; 74% (370 patients) were male; 75% (377 patients) presented with
      unstable coronary syndromes; 10% (50 patients) had an intraaortic balloon pump;
      and 66% (329 patients) were neurologically asymptomatic. Hospital mortality was
      3.6% (18 patients). Significant multivariable predictors of hospital death were
      preoperative transient ischemic attack or myocardial infarction, and nonelective
      operation. Perioperative strokes were 4.6% (23 patients), of which 2.4% (12
      patients) were ipsilateral and 2.2% (11 patients) were contralateral. Significant
      multivariable predictors of stroke were peripheral vascular disease and use of
      the right internal mammary artery. Ten-year actuarial survival was 43%. Ten-year
      actual versus Kaplan-Meier actuarial freedoms with 95% confidence limits from
      late events were myocardial infarction 87% (78% and 92%) versus 81% (75% and
      87%); percutaneous coronary intervention 92% (85% and 96%) versus 89% (84% and
      94%); reoperative coronary grafting 96% (89% and 99%) versus 94% (90% and 98%);
      total stroke 85% (77% and 91%) versus 82% (76% and 87%); ipsilateral stroke 90%
      (83% and 94%) versus 87% (82% and 92%); carotid endarterectomy 82% (73% and 88%)
      versus 75% (69% and 82%). CONCLUSIONS: Concomitant carotid and coronary artery
      surgery is safe and effective, particularly in preventing ipsilateral stroke, and
      neutralizes the impact of unilateral carotid stenosis on early and late stroke.
      Actual, not actuarial, methods more accurately represent the true risk of
      nonfatal late events.

PMID- 16305852
TI  - Long segmental reconstruction of diffusely diseased left anterior descending
      coronary artery with left internal thoracic artery with or without
      endarterectomy.
AB  - BACKGROUND: The diffusely diseased left anterior descending coronary artery (LAD)
      remains a challenge for both interventional cardiologists and cardiac surgeons.
      In this study we assessed the surgical outcomes obtained from coronary artery
      reconstruction, with or without endarterectomy, for a diffusely diseased LAD.
      METHODS: Two hundred and fifty patients were treated with an extended LAD
      reconstruction, with or without endarterectomy, as part of coronary artery bypass
      grafting to achieve complete revascularization. The left internal thoracic artery
      (LITA) was used to reconstruct the LAD in all patients. There were 197 men and 53
      women. The mean age was 65.1 +/- 9.0 years. Coronary artery reconstruction was
      performed without endarterectomy in 183 patients (73.2%) and with endarterectomy
      in 67 patients (26.8%). The off-pump technique was used in 204 patients (81.6%).
      RESULTS: The operative mortality was 1.6%. Perioperative myocardial infarction
      was observed in 6.4% of the patients. The mean LAD incision length was 4.3 +/-
      1.7 cm. The patency rate of the LITA to LAD was 98.6% by early angiographic
      examination (mean, 7.5 +/- 2.6 postoperative days). There were 3 late cardiac
      related deaths at a mean follow-up of 21.2 +/- 10.7 months. The actuarial
      survival was 92.0% at 45 months. Freedom from death or cardiac events was 88.1%
      at 45 months. CONCLUSIONS: Coronary artery reconstruction, with or without
      endarterectomy, using the left internal thoracic artery for a diffusely diseased
      LAD can be performed with acceptable early and midterm results.

PMID- 16305853
TI  - Massachusetts cardiac surgery report card: implications of statistical
      methodology.
AB  - BACKGROUND: Choice of statistical methodology may significantly impact the
      results of provider profiling, including cardiac surgery report cards. Because of
      sample size and clustering issues, logistic regression may overestimate
      systematic interprovider variability, leading to false outlier classification.
      Theoretically, the use of hierarchical models should result in more accurate
      representation of provider performance. METHODS: Extensively validated and
      audited data were available for all 4,603 isolated coronary artery bypass
      grafting procedures performed at 13 Massachusetts hospitals during 2002. To
      produce the official Massachusetts cardiac surgery report card, a 19-variable
      predictor set and a hierarchical generalized linear model were employed. For the
      current study, this same analysis was repeated with the 14 predictors used in the
      New York Cardiac Surgery Reporting System. Two additional analyses were conducted
      using each set of predictor variables and applying standard logistic regression.
      For each of the four combinations of predictors and models, the point estimates
      of risk-adjusted 30-day mortality, 95% confidence or probability intervals, and
      outlier status were determined for each hospital. RESULTS: Overall unadjusted
      mortality for coronary bypass operations was 2.19%. For most hospitals, there was
      wide variability in the point estimates and confidence or probability intervals
      of risk-adjusted mortality depending on statistical model, but little variability
      relative to the choice of predictors. There were no hospital outliers using
      hierarchical models, but there was one outlier using logistic regression with
      either predictor set. CONCLUSIONS: When used to compare provider performance,
      logistic regression increases the possibility of false outlier classification.
      The use of hierarchical models is recommended.

PMID- 16305854
TI  - Limitations of hospital volume as a measure of quality of care for coronary
      artery bypass graft surgery.
AB  - BACKGROUND: While prior research has found an inverse relationship between
      hospital volume and mortality after coronary artery bypass graft surgery (CABG),
      the use of volume as a proxy for quality and a means for selecting hospitals is
      controversial. The objective of this study is to quantify the relationship
      between hospital volume alone and CABG mortality. METHODS: A retrospective cohort
      of 948,093 Medicare patients undergoing CABG in 870 US hospitals from 1996 to
      2001 was categorized into quintiles, based on hospital CABG volume. Hospitals
      were also classified by volume criterion proposed by the Leapfrog Group. Logistic
      regression was used to adjust hospital mortality rates (in-hospital or within 30
      days after CABG) for patient characteristics; discrimination of the volume
      categories was assessed by the c statistic. RESULTS: The range in risk-adjusted
      mortality for hospitals within the quintiles was substantial: 1% to 17% at very
      low, 2% to 12% at low, 2% to 10% at medium, 2% to 9% at high, and 3% to 11% at
      very high volume hospitals. Moreover, volume alone was a poor discriminator of
      mortality (c statistic = 0.52). Similar variation in adjusted mortality was seen
      within the Leapfrog low-volume (1% to 17%) and high-volume groups (2% to 11%),
      and the Leapfrog criterion was a poor discriminator of mortality (c statistic =
      0.51). Of the 660 low-volume Leapfrog hospitals, 253 (38%) had risk-adjusted
      mortality rates that were similar to or lower than the overall risk-adjusted
      mortality of high-volume hospitals (5.2%). CONCLUSIONS: Volume alone, as a
      discriminator of mortality, is only slightly better than a coin flip (c statistic
      of 0.50).

PMID- 16305855
TI  - Invited commentary.

PMID- 16305856
TI  - Meta-analysis of randomized trials comparing off-pump with on-pump coronary
      artery bypass graft patency.
AB  - BACKGROUND: Off-pump coronary artery bypass graft surgery (OPCAB) is increasingly
      becoming a widely used technique and challenges conventional on-pump coronary
      artery bypass grafting as the standard surgical therapy for coronary artery
      disease. Little information, however, is available concerning postoperative
      performance of bypass grafts done with this new technique. The aim of this study
      is to assess differences in graft patency between OPCAB and coronary artery
      bypass grafting by meta-analysis of data published in randomized trials. METHODS:
      A literature search for the period beginning January 1990 until December 2004
      supplemented with manual bibliographic review was performed for all peer-reviewed
      English-language publications. A systematic overview (meta-analysis) of
      randomized trials was conducted to assess differences between OPCAB and coronary
      artery bypass grafting in graft occlusion rates. RESULTS: Literature search
      yielded five comparable randomized studies, for a total of 872 and 998 grafts
      performed during OPCAB and coronary artery bypass grafting procedures,
      respectively. Meta-analysis of these studies showed an increased risk of graft
      occlusion in the OPCAB group of patients, both when all the studies were analyzed
      together (odds ratio, 1.51; 95% confidence intervals, 1.15 to 1.99; p = 0.003),
      and when low-quality (odds ratio, 1.46; 95% confidence intervals, 1.05 to 2.03; p
      = 0.02) and high-quality (odds ratio, 1.65; 95% confidence intervals, 0.99 to
      2.75; p = 0.05) studies were analyzed separately. CONCLUSIONS: Cumulative
      analysis of the few prospective randomized studies currently available in the
      literature documents a reduction in postoperative patency of coronary artery
      bypass grafts performed during OPCAB procedures. The risk of reduced graft
      patency needs to be considered when choosing OPCAB as tailored strategy for
      selected patients.

PMID- 16305857
TI  - Cerebral ischemic injury and cognitive impairment after off-pump and on-pump
      coronary artery bypass grafting surgery.
AB  - BACKGROUND: Off-pump coronary artery bypass grafting surgery reduces the
      intraoperative cerebral embolic load and may therefore cause less brain injury.
      The main aim of this study was to compare off-pump and on-pump surgery with
      regard to the frequency of new postoperative cerebral ischemic lesions and the
      prevalence of postoperative cognitive impairment. We also assessed whether
      preoperative cerebral ischemic injury predicts the risk for cognitive dysfunction
      after surgery. METHODS: One hundred twenty patients with ischemic coronary artery
      disease were prospectively randomized to undergo off-pump or on-pump surgery. A
      detailed neuropsychological assessment and a cerebral magnetic resonance imaging
      examination were performed on the day before and at 3 months postoperatively. The
      neuropsychological assessment was repeated at 12 months. RESULTS: There was no
      significant (p = 0.17) difference between off-pump (8.2%) and on-pump (17.3%)
      surgery with regard to new postoperative cerebral lesions. The prevalence of
      cognitive impairment after surgery was also similar in the two groups (3 months:
      off-pump 20.4%, on-pump 23.1%, p = 0.74; 12 months: off-pump 24.1%, on-pump
      23.1%, p = 0.90). The degree of preoperative cerebral ischemic injury was
      significantly associated with cognitive dysfunction after on-pump (p = 0.02) but
      not after off-pump (p = 0.22) surgery. None of the patients with normal
      preoperative radiologic findings were found to have cognitive impairment at 3
      months postoperatively (p = 0.04). CONCLUSIONS: Long-term cognitive function and
      magnetic resonance imaging evidence of brain injury were similar after off-pump
      and on-pump coronary artery bypass grafting surgery. Preoperative cerebral
      magnetic resonance imaging can be used to predict the risk for cognitive
      dysfunction after coronary artery bypass grafting surgery.

PMID- 16305858
TI  - Perioperative patency of coronary artery bypass grafting is not influenced by off
      pump technique.
AB  - BACKGROUND: Some concerns have been raised about technical accuracy and quality
      of distal anastomoses in off-pump myocardial revascularization (OPCAB), which
      could affect graft patency. METHODS: Transit-time flowmetric results and
      clinical, enzymatic, and echocardiographic findings from 201 consecutive isolated
      on-pump coronary artery bypass graft cases (cardiopulmonary bypass coronary
      artery bypass grafting; group A) were compared with 96 consecutive OPCAB (group
      B) cases performed at our institution between January 2003 and December 2004.
      Maximum, mean, minimum flow, and pulsatility index were compared, stratifying the
      two groups according to graft type and coronaries revascularized. Graft flow
      reserve was evaluated in patients undergoing preoperative intraaortic balloon
      pump during baseline conditions and at a 1 to 1 ratio of intraaortic balloon pump
      augmentation. RESULTS: No differences were recorded between the two groups in
      hospital mortality, perioperative myocardial infarction, postoperative enzymatic
      leakage, echocardiographic recovery, or hospital stay (p = not significant). Off
      pump coronary artery bypass and cardiopulmonary bypass coronary artery bypass
      grafting demonstrated similar intraoperative maximum (75.8 +/- 10.4 mL/min vs
      82.3 +/- 15.8; p = 0.190), mean (50.1 +/- 13.3 vs 46.3 +/- 7.7; p = 0.420),
      minimum flow (12.7 +/- 5.3 vs 11.9 +/- 5.4; p = 0.811), and pulsatility index
      (2.9 +/- 0.2 vs 2.6 +/- 0.8; p = 0.360). After stratifying the population
      according to graft type, no differences were detected between the two groups in
      transit-time flowmetric results of left internal mammary artery, radial artery,
      and single and sequential saphenous vein grafts. A one to one ratio of
      intraaortic balloon pump augmentation did not result in any difference in graft
      flow reserve when left internal mammary artery (p = 0.699), radial artery (p =
      0.066), and saphenous vein graft anastomoses (p = 0.772) were considered.
      CONCLUSIONS: Off-pump coronary artery bypass grafting and cardiopulmonary bypass
      coronary artery bypass grafting demonstrated similar clinical, biochemical, and
      transit-time flowmetric results, as well as comparable graft flow reserve. These
      data exclude a lower anastomotic quality in off-pump coronary artery bypass
      grafting.

PMID- 16305859
TI  - Incomplete revascularization during OPCAB surgery is associated with reduced mid
      term event-free survival.
AB  - BACKGROUND: The aim of this study was to compare early and mid-term outcome in
      patients undergoing off-pump coronary artery bypass surgery who have had complete
      revascularizations and incomplete revascularizations (IRs). METHODS: Patient and
      operative data were collected prospectively for all patients who had off-pump
      coronary artery bypass surgery. Patients with multivessel disease were classified
      as having IR if the number of diseased coronary systems (left anterior descending
      coronary artery, circumflex and right coronary artery) exceeded the number of
      distal anastomoses. In-hospital outcomes, survival, and event-free survival were
      compared between patients with complete revascularization and IR using propensity
      scores to take account of differences in prognostic factors. RESULTS: There were
      1,479 off-pump coronary artery bypass surgery patients between April 1996 and
      December 2002 (30% of all coronary artery bypass graft patients), and 16.0% (237
      patients) had IRs. Patients with IRs tended to be older and were female, had more
      extensive disease, worse dyspnea, a higher Parsonnet score, poorer ejection
      fraction, congestive cardiac failure, asthma or chronic obstructive airways
      disease, and previous cardiac surgery. The adjusted hazard ratio for patient
      survival with IRs versus complete revascularizations was 1.56 (95% confidence
      interval, 1.19 to 2.06; p = 0.001). Analyses for multiple time periods confirmed
      that IRs had a significantly increased risk of death, but also that the risk
      disappeared after the first 4 to 6 months of follow-up (p < 0.0001). CONCLUSIONS:
      Compared with off-pump coronary artery bypass surgery patients with complete
      revascularizations, those with IRs have reduced survival, but only in the first 4
      to 6 months after surgery. Patients' preoperative condition, rather than IR
      itself, may explain these findings because IRs should have mid-term as well as
      early effects.

PMID- 16305860
TI  - Renal dysfunction in high-risk patients after on-pump and off-pump coronary
      artery bypass surgery: a propensity score analysis.
AB  - BACKGROUND: Cardiopulmonary bypass may be a causal factor in the development of
      renal impairment after cardiac surgery. When acute renal failure requiring
      dialysis occurs after cardiac surgery, it is associated with high mortality. We
      attempted to determine whether off-pump coronary artery bypass grafting surgery
      prevents postoperative renal dysfunction in patients at high risk for renal
      failure. METHODS: Retrospective analysis identified 2,869 patients who had
      preexisting renal dysfunction (preoperative creatinine clearance less than 60
      mL/min) and who underwent isolated coronary artery bypass grafting between 1995
      and 2003. Patients who required preoperative dialysis were excluded. Propensity
      scores were computed to match off-pump coronary artery bypass surgery patients
      3:1 with those who underwent conventional coronary artery bypass grafting
      surgery, and the independent predictors of postoperative renal dysfunction were
      determined. RESULTS: Two thousand seven hundred eleven patients with preexisting
      renal dysfunction underwent conventional coronary artery bypass grafting surgery,
      and 158 patients underwent coronary artery bypass grafting surgery without
      cardiopulmonary bypass (off-pump coronary artery bypass grafting surgery group).
      The matched groups showed no differences in any of the preoperative or
      postoperative variables examined. Diabetes (odds ratio, 1.96; p = 0.01),
      peripheral vascular disease (odds ratio, 2.50; p < 0.001), and reduced
      preoperative creatinine clearance (odds ratio, 1.02; p = 0.02) were independent
      risk factors for the development of postoperative renal dysfunction. Off-pump
      coronary artery bypass grafting surgery was not associated with a decreased risk
      of renal dysfunction by univariate or multivariable analysis. CONCLUSIONS: Off
      pump coronary artery bypass grafting surgery did not reduce the risk of
      postoperative renal dysfunction in this large, unselected, sequential series of
      patients at high risk for renal failure after coronary artery bypass grafting
      surgery. Our results suggest that renal function should not be a deciding factor
      when determining whether or not a patient undergoes off-pump coronary artery
      bypass grafting surgery.

PMID- 16305861
TI  - Invited commentary.

PMID- 16305862
TI  - Intraoperative transit time flow measurement: off-pump versus on-pump coronary
      artery bypass.
AB  - BACKGROUND: Off-pump coronary artery bypass grafting (OPCAB) has attracted
      increasing attention. Performing the anastomosis off-pump is technically more
      demanding. The objective of the study is to assess the quality of anastomosis in
      OPCAB in comparison with conventional on-pump coronary artery bypass grafting
      using the transit time flow measurement. METHODS: Four hundred forty-five
      patients operated on using OPCAB technique were included in the study. For each
      patient in this group a similar patient from the on-pump coronary artery bypass
      grafting population was selected according to the number of grafts, bypass
      material, and target coronary arteries. The mean flow and the pulsatile index
      were measured in every bypass graft in both groups. RESULTS: The average
      pulsatile index in OPCAB was 2.09 +/- 1.03 (mean flow, 39 +/- 22.63 mL/min),
      whereas with on-pump coronary artery bypass grafting it was 1.9 +/- 0.98 (mean
      flow, 44.19 +/- 23.58 mL/min); p = 0.005. Subgroup analysis showed significantly
      lower mean flows and higher pulsatile index with OPCAB in grafts to the obtuse
      marginal, diagonal, and right coronary artery, but not to the left anterior
      descending territory. CONCLUSIONS: The quality of the anastomosis performed using
      the OPCAB technique might be jeopardized by less accessibility as in the case of
      lateral and posterior wall coronary arteries. Techniques to optimize the
      accessibility of the coronary artery like combining sling support with cup
      stabilizers, together with systematic training, should be strongly considered in
      OPCAB. Whenever there is good accessibility of the coronary artery as in the case
      of the left anterior descending, the anastomosis performed under OPCAB has a
      quality as good as that performed using the conventional technique.

PMID- 16305863
TI  - Invited commentary.

PMID- 16305864
TI  - Single-layer versus multiple-layer closure of leg wounds after long saphenous
      vein harvest: a prospective randomized trial.
AB  - BACKGROUND: The long saphenous vein harvested by traditional techniques is an
      important conduit for coronary artery bypass grafting (CABG). The purpose of this
      study was to determine if a single-layer closure over a drain improved wound
      healing compared with the traditional two-layer closure after harvest. METHODS:
      Seventy-eight consecutive patients undergoing CABG were prospectively randomized
      to have their leg wound closed by either a single-layer technique with a suction
      drain or multiple layers. All wounds were assessed using the additional
      treatment, presence of serous discharge, erythema, purulent exudate, and
      separation of the deep tissues, isolation of bacteria, and the duration of
      inpatient stay (ASEPSIS) score postoperatively and 6 weeks later. RESULTS: Forty
      four patients (5 females) had their wound closed by the single-layer technique
      and 34 (6 females) closed in multiple layers. The ASEPSIS scores were
      significantly lower (p = 0.001) in those patients closed with a single layer
      (mean, 4.4) than those with multiple layers (mean, 6.8). Patients whose legs were
      closed with the single-layer technique had less peripheral edema compared with
      the multiple-layer group (chi2, p < 0.001). Using univariate analysis there was
      no correlation between ASEPSIS scores and length of wound incision (p = 0.49),
      whereas increasing age was found to have a weak positive correlation (r =0.24; p
      = 0.04). CONCLUSIONS: Single-layer leg wound closure over a suction drain is
      superior to the traditional multiple-layer closure. A possible mechanism of
      better wound healing in the former technique might be through decreased tissue
      handling and a reduction in leg edema.

PMID- 16305865
TI  - The reversed elephant trunk technique used for treatment of complex aneurysms of
      the entire thoracic aorta.
AB  - OBJECTIVE: A preferred technique for the staged treatment of patients with
      aneurysms involving the entire thoracic aorta is the elephant trunk technique,
      with replacement of the proximal (ascending and transverse aortic arch) aorta as
      the initial procedure. Some patients, however, need to have the distal aortic
      segments (descending and thoracoabdominal aorta) addressed during the first
      operation. We evaluated outcomes in a series of patients who underwent distal
      aortic replacement first using the reversed elephant trunk technique. METHODS:
      Thirty-eight patients underwent first-stage graft repair of the descending
      thoracic (n = 3) or thoracoabdominal (n = 35) aorta using the reversed elephant
      trunk technique. Twelve patients (32%) ultimately underwent second-stage aortic
      arch replacement after a mean interval of 3.9 months (range, 1.6-14 months).
      RESULTS: The operative mortality for the initial procedure was 16% (6/38
      patients). One patient had a stroke (3%) and 1 patient developed paraparesis
      (3%). In the interval between the 2 procedures, there were 4 late deaths (4/32;
      13%), 1 due to respiratory failure and 3 due to unknown causes. After the 12
      completion procedures, there was 1 in-hospital death (8%) and there were no
      strokes. Five-year survival for the overall group was 51.3 +/- 10.8%.
      CONCLUSIONS: Surgical treatment of aneurysms involving the entire thoracic aorta
      remains challenging and is associated with substantial morbidity and mortality.
      The reversed elephant trunk technique facilitates staged repair in patients who
      require distal aortic replacement during the first operation.

PMID- 16305866
TI  - Evolution of risk for neurologic deficit after descending and thoracoabdominal
      aortic repair.
AB  - BACKGROUND: Cross-clamp time has been reported to correlate with risk of
      neurologic deficit after thoracoabdominal aortic aneurysm repair. Introduction of
      cerebrospinal fluid drainage and distal aortic perfusion (adjunct) has greatly
      reduced the incidence of neurologic deficit. We reevaluated the effect of cross
      clamp time before and after introduction of adjunct during a 13-year period.
      METHODS: Between 1991 and 2004, we repaired 1,106 thoracic and thoracoabdominal
      aortic aneurysms. Four hundred one patients were female and 705 were male (median
      age, 67 years). Selective use of adjunct was begun in late 1992, with its routine
      use by 1993. RESULTS: Aortic cross-clamp times have increased significantly (34
      seconds/year; p < 0.0001) since 1991. Despite this increase in cross-clamp time,
      neurologic deficit rates have declined from the first to the fourth quartile (p <
      0.02). This decrease in neurologic deficit is most pronounced with the extent II
      thoracoabdominal aortic aneurysms (21.1% to 3.3%). The use of the adjunct
      increased the cross-clamp time by a mean of 12 minutes (p < 0.0001), but was
      associated with a significant protective effect against neurologic deficit (odds
      ratio = 0.4; p < 0.0002). Although other previously established risk factors
      remained significantly associated with neurologic deficit, cross-clamp time is no
      longer significant. CONCLUSIONS: Adjunct significantly reduced the risk of
      neurologic deficit, despite increasing cross-clamp time. The use of the adjunct
      appears to blunt the effect of the cross-clamp time and may provide the surgeon
      the ability to operate without being hurried. Because cross-clamp time has been
      effectively eliminated as a risk factor with the use of the adjunct, using this
      variable to construct risk models becomes irrelevant in our experience.

PMID- 16305867
TI  - Stentless aortic valves are hemodynamically superior to stented valves during mid
      term follow-up: a large retrospective study.
AB  - BACKGROUND: Several studies have compared left venticular mass (LVM) regression
      and hemodynamic data for stentless versus stented aortic bioprostheses with
      conflicting results. The major limitations of these studies are their small
      sample size and short-term follow-up. We therefore compared midterm LVM
      regression, hemodynamic data, and survival in a large population of tissue aortic
      valve replacement (AVR) patients. METHODS: All patients undergoing tissue AVR at
      our institution between 1998 and 2001 were included (n = 737). Patients were
      divided into two groups according to type of bioprosthetic implanted: stentless
      patients (total n = 310) (Toronto SPV [St Jude Medical, St Paul, MN], n = 146 and
      Freestyle [Medtronic, Minneapolis, MN], n = 164) and stented patients (total n =
      427) (Perimount [Edwards Life Sciences Inc, Irvine, CA], n = 291 and Mosaic
      [Medtronic], n = 136). RESULTS: The two groups of patients had similar
      preoperative transvalvular gradients and LVM index (130 +/- 47 vs 130 +/- 42 g/m2
      for stentless versus stented valves, respectively). Predischarge echos revealed
      that stentless patients had significantly lower mean transvalvular gradients (11
      +/- 5 vs 15 +/- 6 mm Hg, p < 0.001) and larger effective orifice areas (1.32 +/-
      0.52 vs 1.22 +/- 0.48 cm2, p = 0.01). Follow-up echocardiograms were obtained in
      99% of surviving patients 28 +/- 22 (range, 0-79) months postoperatively.
      Stentless patients had significantly lower LVM index during follow-up (100 +/- 32
      vs 107 +/- 32 g/m2, p = 0.005) and stentless valves were an independent predictor
      of LVM regression. Furthermore, a higher proportion of stented patients had
      residual LV hypertrophy during follow-up (28% vs 18%, p = 0.001). Stentless
      valves were associated with improved midterm survival by univariate analysis, but
      not by multivariable analysis. CONCLUSIONS: Midterm follow-up in a large number
      of patients reveals that stentless bioprostheses are hemodynamically superior to
      stented valves.

PMID- 16305868
TI  - Myocardial systolic strain is decreased after aortic valve replacement in
      patients with aortic insufficiency.
AB  - BACKGROUND: Left ventricular three-dimensional nonlinear systolic strain
      determinations have potential to detect small decrements in ventricular function
      in patients with aortic insufficiency before and after aortic valve replacement.
      METHODS: Magnetic resonance imaging with tissue-tagging was performed on 42
      normal volunteers and 14 patients with chronic aortic insufficiency both before
      and 28 +/- 11 months after aortic valve replacement. Preoperative and
      postoperative left ventricular volume, dimensions and ejection fraction were
      determined for all subjects. Left ventricular systolic radial, circumferential,
      longitudinal, and minimum principal strain were calculated for six left
      ventricular regions. RESULTS: After aortic valve replacement, left ventricular
      volume and dimensions decreased significantly (p < 0.001) and ejection fraction
      increased nonsignificantly (p = 0.096). Strain values in preoperative aortic
      insufficiency patients did not differ significantly from controls. At an average
      of 28 +/- 11 months postoperatively, however, regional three-dimensional minimum
      principal and longitudinal strain was decreased in all six ventricular regions as
      well as globally (p < 0.03) compared with normal control values. Circumferential
      strain was significantly decreased globally and in all but two regions (p <
      0.03). CONCLUSIONS: These magnetic resonance imaging-based techniques are
      sensitive enough to detect a previously unrecognized, significant decrease in
      both global and regional three-dimensional left ventricular systolic strain 2
      years after aortic valve replacement for minimally symptomatic chronic aortic
      insufficiency despite improvement in ejection fraction and a decrease in left
      ventricular size. The reasons for a significant decline in left ventricular
      systolic strain after successful aortic valve replacement in minimally
      symptomatic chronic aortic insufficiency patients are not clear and warrant
      further investigation.

PMID- 16305869
TI  - Invited commentary.

PMID- 16305870
TI  - Do pulmonary autografts provide better outcomes than mechanical valves? A
      prospective randomized trial.
AB  - BACKGROUND: The objective of this study was to compare the performance of
      pulmonary autografts with mechanical aortic valves, in the treatment of aortic
      valve stenosis. METHODS: Forty patients with aortic valve stenoses, and below the
      age of 55 years, were randomly assigned to receive either pulmonary autografts (n
      = 20) or mechanical valve (Edwards MIRA; Edwards Lifesciences, Irvine, CA)
      prostheses (n = 20). Clinical outcomes, left ventricular mass regression,
      effective orifice area, ejection fraction, and mean gradients were evaluated at
      discharge, 6 months, and one year after surgery. Follow-up was complete for all
      patients. RESULTS: Hemodynamic performance was significantly better in the Ross
      group (mean gradient 2.6 mm Hg vs 10.9 mm Hg, p = 0.0005). Overall, a significant
      decrease in left ventricular mass was found one year postoperatively. However,
      there was no significant difference in the rate and extent of regression between
      the groups. There was one stroke in the Ross group and one major bleeding
      complication in the mechanical valve group. Both patients recovered fully.
      CONCLUSIONS: In our randomized cohort of young patients with aortic valve
      stenoses, the Ross procedure was superior to the mechanical prostheses with
      regard to hemodynamic performance. However, this did not result in an accelerated
      left ventricular mass regression. Clinical advantages like reduced valve-related
      complications and lesser myocardial strain will have to be proven in the long
      term.

PMID- 16305871
TI  - Surgical treatment of mitral valve endocarditis in North America.
AB  - BACKGROUND: Several single-institution series have suggested the feasibility and
      effectiveness of mitral valve repair for infective endocarditis (IE). METHODS: We
      examined 6627 patients with IE undergoing mitral valve surgery at 661 Society of
      Thoracic Surgeons-participating centers in 1994 to 2003. RESULTS: The diagnosis
      of IE was assigned to 5.8% (6,627 of 114,934) of patients having mitral valve
      surgery. The overall frequency of mitral valve repair for IE was 29.7% (1,965 of
      6,627). Mitral valve repair was less frequently used for patients with active IE
      (423 of 2,654; 15.9%) than those with treated IE (1,459 of 3,570; 40.9%).
      Operative mortality was 3.7% (72 of 1,965) for mitral valve repair and 10.8% (502
      of 4,662) for mitral valve replacement. Mortality rates were lower for patients
      with treated IE compared with active IE. After adjusting for multiple
      preoperative risk factors, mitral valve repair (odds ratio, 0.67; 95% confidence
      interval, 0.51 to 0.88) was associated with a significantly lower risk of death.
      Active (versus treated) IE (odds ratio, 2.12; 95% confidence interval, 1.68 to
      2.68) and recent cerebrovascular accident (odds ratio, 1.71; 95% confidence
      interval, 1.28 to 2.31) were independent predictors of mortality. CONCLUSIONS:
      Mitral valve repair is less commonly applied for IE compared with other
      indications for mitral valve surgery. Patients with active IE were less likely to
      receive repair than those with treated IE. Mitral valve repair was associated
      with a lower risk of mortality. These results provide support for performing
      mitral valve repair when technically feasible in the setting of IE.

PMID- 16305872
TI  - Vacuum-assisted wound closure of deep sternal infections in high-risk patients
      after cardiac surgery.
AB  - BACKGROUND: Sternal wound infections are a serious complication arising from
      cardiac surgery. Recently, the general application of negative pressure to wounds
      by vacuum-assisted closure (VAC) therapy has shown enhanced granulation and wound
      contraction. Here we examine the effect of VAC on sternal wounds. METHODS: We
      collected and statistically analyzed quantitative VAC performance data and
      outcomes with a retrospective review on a consecutive cohort of 22 patients
      treated with VAC for post-cardiac surgery wound complications. RESULTS: Sternal
      wound infections became evident on average at 21.0 days after surgery, associated
      with dehiscence (82%), sternal instability (59%), fluid collection by computed
      tomography (73%), and osteomyelitis (41%). Cultures most commonly identified
      Staphylococcus aureus (50%). Prompt irrigation and debridement were performed on
      all patients, and VAC therapy was applied at approximately 7.3 days after
      diagnosis. Vacuum-assisted closure induced granulation of 71% of the sternal
      wound area by 7 days, with a daily drainage of approximately 84 mL. By 14 days,
      there was a 54% reduction in wound size, and patients were discharged after
      approximately 19.5 days and placed on home therapy. Vacuum-assisted closure was
      discontinued at approximately 36.7 days with an average reduction in sternal
      wound size of 80%. Extensive secondary surgical closure, requiring muscle flaps,
      was avoided in 64% of patients, whereas 28% of patients required no surgical
      reconstruction for wound closure. No complications were related to VAC use.
      CONCLUSIONS: In contrast to our earlier studies, adjunctive VAC therapy markedly
      reduced required surgical interventions, reoperation for persistent infections,
      and the hospitalization period. Thus, VAC provides a viable and efficacious
      adjunctive method by which to treat postoperative wound infection after medial
      sternotomy.

PMID- 16305873
TI  - Invited commentary.

PMID- 16305874
TI  - Oxygen delivery during cardiopulmonary bypass and acute renal failure after
      coronary operations.
AB  - BACKGROUND: The degree of hemodilution during cardiopulmonary bypass has recently
      been identified as an independent risk factor for acute renal failure after
      cardiac operations. In this prospective observational study we have investigated
      the role of the lowest oxygen delivery, lowest hematocrit, and pump flow during
      cardiopulmonary bypass as possible risk factors for acute renal failure and renal
      dysfunction. METHODS: One thousand forty-eight consecutive patients undergoing
      coronary operations have been studied. For each patient we have recorded the
      lowest hematocrit on cardiopulmonary bypass, the correspondent lowest oxygen
      delivery, and the pump flow around the time of these determinations. The three
      variables have been explored in a multivariable model as possible risk factors
      for acute renal failure and postoperative serum creatinine levels increase. The
      role of transfusions in determining acute renal failure was subsequently included
      in the model. RESULTS: The best predictor for acute renal failure and peak
      postoperative serum creatinine levels was the lowest oxygen delivery, with a
      critical value at 272 mL.min(-1).m(-2). The lowest hematocrit was an independent
      risk factor with a lowest predictive value at a cutoff of 26%. When corrected for
      the need for transfusions, only the lowest oxygen delivery remained an
      independent risk factor. CONCLUSIONS: A high degree of hemodilution during
      cardiopulmonary bypass is a risk factor for postoperative renal dysfunction;
      however, its detrimental effects may be reduced by increasing the oxygen delivery
      with an adequately increased pump flow.

PMID- 16305875
TI  - Invited commentary.

PMID- 16305876
TI  - Should we discontinue intraaortic balloon during cardioplegic arrest? Splanchnic
      function results of a prospective randomized trial.
AB  - BACKGROUND: Preoperative use of intraaortic balloon pumping (IABP) has increased
      in high-risk patients. Linear flow during cardiopulmonary bypass (CPB) can induce
      subclinical damage, whereas automatic IABP mode may maintain pulsatile flow. We
      sought to evaluate differences between suspending IABP and switching it to an
      automatic 80 bpm mode during cardioplegic arrest. METHODS: Between January and
      November 2004, 40 patients undergoing preoperative IABP were randomized to
      receive either standard nonpulsatile CPB with IABP discontinued during
      cardioplegic arrest (20 patients; group A) or IABP-induced pulsatile (automatic
      80 bpm) CPB (20 patients; group B). Hospital outcome was recorded. Urine output,
      blood urea nitrogen (BUN), creatine, creatinine clearance, peripheral lactate,
      recovery of gut motility, alanine-amino-transferase (ALT), aspartate-amino
      transferase (AST), lactic dehydrogenase (LDH), bilirubin, and amylase (AMY) were
      compared. RESULTS: There were no IABP-related complications, nor perioperative
      renal or liver failures, nor hospital deaths, nor myocardial infarctions.
      Intensive care and hospital stay, urine output, and recovery of gut motility were
      comparable. Group B showed lower creatine on the first (p = 0.01) and second (p =
      0.005) postoperative days, higher creatinine clearance (first day: p = 0.01;
      second day: p = 0.03), lower lactate after CPB termination (p = 0.0001) and
      during the first day (p = 0.001). The ALT, AST, and AMY were lower in group B
      (first day ALT: p = 0.01; AST: p = 0.04; AMY: p = 0.017; second day ALT: p =
      0.01; AST: p = 0.02; AMY: p = 0.027), as well as total bilirubin (first day: p =
      0.05; second day: p = 0.02). CONCLUSIONS: Automatic 80 bpm IABP during
      cardioplegic arrest improves creatinine clearance and splanchnic enzymes. There
      is no reason to suspend preoperative IABP support during cardioplegic arrest.

PMID- 16305877
TI  - Invited commentary.

PMID- 16305878
TI  - Cardiomyocyte apoptosis after antegrade and retrograde cardioplegia.
AB  - BACKGROUND: Retrograde cardioplegia alone is often used in aortic valve and
      aortic root surgery. Due to the differences in venous anatomy between the right
      and the left side of the heart, retrograde cardioplegia is associated with
      incomplete protection of the right side. Since some apoptotic cardiomyocyte death
      is inevitable during an open heart surgery, we compared the extent of
      cardiomyocyte apoptosis in the left and right ventricles after antegrade and
      retrograde cardioplegia in a pig ischemia-reperfusion model. METHODS: Pigs (n =
      16, mean weight 30 kg) were openly assigned into the groups of antegrade and
      retrograde cardioplegia. After aortic cross-clamping, 500 mL of cold crystalloid
      (modified St Thomas) cardioplegia was administered into the ascending aorta or
      the coronary sinus. Aortic cross-clamp time was 30 minutes. Cardiomyocyte
      apoptosis was measured using the terminal transferase mediated ddUTP nick end
      labeling (TUNEL) assay and immunohistochemical (IHC) staining for active caspase
      3 in myocardial biopsies obtained before ischemia and after 90 minutes of
      reperfusion. RESULTS: Apoptotic cardiomyocytes were significantly increased after
      ischemia-reperfusion as shown by both the TUNEL assay and caspase-3 activation.
      In the right ventricle, retrograde cardioplegia was associated with a 3.4-fold
      higher amount (TUNEL assay) of apoptotic cardiomyocytes as compared with
      antegrade cardioplegia (0.107% vs 0.032%, p < 0.05). A similar difference was
      also found in the left ventricle, although at a lower level (0.027% vs 0.012%, p
      < 0.05). CONCLUSIONS: Increased apoptotic death of cardiomyocytes after
      retrograde cardioplegia as compared with the antegrade procedure implicates that
      retrograde cardioplegia alone provides inferior cardioprotection against
      irreversible ischemia-reperfusion injury both in the right and the left
      ventricle.

PMID- 16305879
TI  - Invited commentary.

PMID- 16305880
TI  - p38 mitogen activated protein kinase mediates both death signaling and functional
      depression in the heart.
AB  - BACKGROUND: Understanding the myocardial inflammatory response to ischemia is an
      important part of achieving the elusive clinical goal of long-enduring myocardial
      protection. p38 mitogen-activated protein kinase (MAPK) has been implicated in
      oxidant stress-induced myocardial tumor necrosis factor production. However, it
      is unknown whether p38 MAPK mediates the following important events in both
      myocardial apoptosis and functional depression: mitogen-activated protein kinase
      activated protein kinase 2, caspase-1, caspase-3, and caspase-11 activation, and
      tumor necrosis factor, interleukin-1beta and interleukin-6 production. METHODS:
      Isolated rat hearts were perfused and subjected to an ischemia-reperfusion
      insult, with and without preischemic infusion of 20 microM SB203580 (p38 MAPK
      inhibitor). Myocardial functional measurements were continuously recorded
      throughout the experiments. Myocardial tissue was then assessed for products of
      p38 MAPK activation, expression of tumor necrosis factor, interleukin-1beta and
      interleukin-6, and activation of caspase-1, caspase-3 and caspase-11. RESULTS:
      Postischemic recovery of left ventricular developed pressure, +dP/dt and -dP/dt
      was significantly increased by p38 MAPK inhibition (MKI) (left ventricular
      developed pressure: 48.4 +/- 3.87 MKI versus 32.7 +/- 4.32 mm Hg; +dP/dt: 1392.0
      +/- 141.7 MKI versus 896.7 +/- 128.5 mm Hg/s; -dP/dt: -889.9 +/- 97.63 MKI versus
      -548.9 +/- 71.29 mmHg/s). p38 MAPK inhibition also significantly reduced ischemia
      reperfusion-induced elevation of left ventricular end-diastolic pressure (82.76
      +/- 4.59 MKI vs 69.95 +/- 3.55 mm Hg). p38 MKI decreased myocardial tumor
      necrosis factor, interleukin-1beta and interleukin-6 protein levels, and reduced
      active myocardial caspase-1, caspase-3 and caspase-11. CONCLUSIONS: The p38 MAPK
      pathway indeed mediates the following important events in myocardial apoptosis
      and functional depression: mitogen-activated protein kinase-activated protein
      kinase 2, caspase-1, caspase-3 and caspase-11 activation, and tumor necrosis
      factor, interleukin-1beta, interleukin-6 production after myocardial ischemia.
      Single site (p38 MAPK) inhibition of these events may have important therapeutic
      implications in myocardial protection.

PMID- 16305881
TI  - Resveratrol, a natural red wine polyphenol, reduces ischemia-reperfusion-induced
      spinal cord injury.
AB  - BACKGROUND: Severe neurologic injury still represents one of the most devastating
      complications after surgical repair of thoracoabdominal aneurysms. We therefore
      aimed to investigate the protective effect of resveratrol, a natural polyphenol
      antioxidant present in grapes and wine, in an experimental model of spinal cord
      ischemia-reperfusion injury. METHODS: Sixteen rabbits were assigned either to
      group A (n = 8; receiving resveratrol, treated group) or group B (n = 8; control
      group, nontreated group) and underwent a 30-minutes period of spinal cord
      ischemia by clamping the abdominal aorta between the left renal artery and the
      aortic bifurcation. Fifteen minutes before clamping, rabbits received either
      intravenous resveratrol (100 microg/kg; group A) or normal saline (group B).
      Functional assessment with Tarlov score at 8, 16, and 24 hours postoperatively,
      histopathologic assessment of the spinal cord, measurements of malondialdehyde
      levels, and myeloperoxidase activity in the spinal cord were performed. RESULTS:
      Neurologic impairment (Tavlov score for group A = 4.38 +/- 1.19 and for group B =
      0.38 +/- 0.74, p < 0.001), malondialdehyde levels (47.71 +/- 7.81 nmol/g versus
      86.56 +/- 11.39 nmol/g, p < 0.001), and myeloperoxidase activity (2.13 +/- 0.72
      nm/min versus 3.75 +/- 0.78 nm/min, p = 0.002) were significantly lower in the
      resveratrol-treated animals. Additionally, pathologically assessed outcomes were
      better in the resveratrol-treated group. The total number of motor neurons in the
      gray matter was significantly lower in the nontreated group than in the
      resveratrol-treated group (14.26 +/- 2.94 versus 29.12 +/- 3.64, p = 0.003).
      CONCLUSIONS: Prophylactic use of resveratrol reduced neurologic injury and
      provided clinical improvement by attenuating the inflammatory milieu in the
      rabbit spinal cord ischemia/reperfusion model.

PMID- 16305882
TI  - Invited commentary.

PMID- 16305883
TI  - Borderzone geometry after acute myocardial infarction: a three-dimensional
      contrast enhanced echocardiographic study.
AB  - BACKGROUND: Regional myocardial geometry, function, and perfusion status are
      critical variables for understanding infarction-induced left ventricle (LV)
      remodeling. Three-dimensional contrast echocardiography (3DCE) is uniquely suited
      to measure these parameters. We evaluate the ability of 3DCE to assess geometric
      changes in the normally perfused but hypocontractile borderzone myocardium (BZM)
      immediately after a myocardial infarction (MI) in an ovine model, and we compare
      3DCE with two-dimensional contrast echocardiography (2DCE) in the long and short
      axis. METHODS: Four sheep were studied with 3DCE and 4 were studied using 2DCE,
      before and 30 minutes after an anteroapical MI. Each 3DCE data set was acquired
      over 18 consecutive cardiac cycles. The LV geometry was reconstructed and
      perfusion data spatially correlated, thereby constituting a 3D model of
      ventricular geometry and perfusion. The borderzone was defined as the contrast
      perfused myocardium adjacent to the infarct. RESULTS: The 2DCE short-axis
      analysis demonstrated decreased curvature and decreased wall thickness in the
      borderzone after MI. These findings are consistent with increased BZM wall
      stress. However, the long-axis 2DCE analysis demonstrated increased BZM wall
      thickness and a surprising change in BZM concavity acutely after infarction. The
      3DCE analysis confirmed these findings and added additional information regarding
      regional variability in BZM geometry that was not evident in the two orthogonal
      2D views. CONCLUSIONS: This study provides evidence that regional changes in BZM
      geometry are more complex than previously believed and are not necessarily
      indicative of increased regional stress. The superiority of 3DCE over 2DCE for
      assessing these changes is strongly supported.

PMID- 16305884
TI  - Invited commentary.

PMID- 16305885
TI  - Early postinfarction ventricular restraint improves borderzone wall thickening
      dynamics during remodeling.
AB  - BACKGROUND: Early infarct expansion impairs function of normally perfused
      borderzone myocardium (BZM), initiates adverse remodeling, and portends a poor
      long-term outcome. Early ventricular restraint has been demonstrated to improve
      global remodeling but its effect on BZM function has not been assessed. Using an
      ovine model of infarct induced remodeling and MRI, we tested the hypothesis that
      ventricular restraint early after MI preserves BZM function and reduces
      remodeling. METHODS: Six sheep had a large anterior infarction after ligation of
      all diagonal branches. One week after infarction 3 sheep had placement of a
      cardiac support device (CSD) to restrain infarct expansion. Global remodeling and
      borderzone wall thickening strain were assessed using tagged MRI before and 8
      weeks after infarction. RESULTS: Global remodeling was greatly reduced in the CSD
      group compared with control. The BZM systolic wall thickening was similar in both
      groups at baseline (13.5% +/- 2.0%, control; 12.8% +/- 2.0%, CSD, p = 0.8). After
      8 weeks of infarction-induced remodeling, systolic wall thickening strain
      decreased significantly to 4.9% +/- 0.7% in the control group (p = 0.03). In
      contrast, systolic wall thickening was preserved in the CSD group at 8 weeks
      (11.0% +/- 1.6%, p = 0.3). In the control group all thickening occurred during
      isovolemic contraction, plateauing during ejection. The CSD improved late
      systolic borderzone wall thickening, although dynamics remained perturbed.
      CONCLUSIONS: Ventricular restraint early after MI improves both contractile
      function of the BZM and global ventricular remodeling. The dynamics of BZM wall
      thickening are impaired during remodeling. The CSD significantly improves but
      does not completely maintain baseline BZM wall thickening dynamics.

PMID- 16305886
TI  - Irrigated radiofrequency ablation with transmurality feedback reliably produces
      Cox maze lesions in vivo.
AB  - BACKGROUND: Irrigated bipolar radiofrequency ablation has been used to replicate
      Cox maze surgical scars in pig hearts ex vivo. Impedance monitoring accurately
      predicted complete transmurality for all lesions. This study aimed to assess the
      feasibility and reliability of irrigated radiofrequency ablation and impedance
      monitoring to produce electrically isolating Cox maze lesions in vivo. METHODS: A
      modified Cox maze procedure was performed in 8 adult sheep during cardiopulmonary
      bypass using irrigated bipolar and unipolar radiofrequency ablation. For bipolar
      radiofrequency ablation, atrial tissues were clamped between opposing electrodes;
      ablation was terminated at the plateau in impedance decline. Unipolar
      radiofrequency ablation lesions were painted on the endocardium, and
      transmurality was assessed visually. Animals survived 30 days. RESULTS: Bipolar
      lesions (n = 48) were thinner (7.4 +/- 2.4 mm versus 12.7 +/- 3.2 mm) and
      required less time (14.1 +/- 3.4 seconds versus 41.4 +/- 21.8 seconds) and energy
      (377.5 +/- 99.2 W.s versus 995.1 +/- 547.1 W.s) to create despite being longer
      (31.7 +/- 8.6 mm versus 19.2 +/- 5.6 mm) than unipolar lesions (n = 26). The left
      atrial pacing threshold across selected bipolar lesions increased at least
      fivefold above baseline (1.6 +/- 0.2 mA) at 1 hour (18.4 +/- 4.6 mA; n = 8; p <
      0.001) and 30 days (17.2 +/- 5.2 mA; n = 6; p < 0.001), indicating functional
      conduction block. Bipolar lesions had no adherent thrombus or endocardial
      defects. Cross-section examination confirmed transmurality in 100% of bipolar
      lesions and 98.7% of unipolar lesions. CONCLUSIONS: Irrigated bipolar
      radiofrequency ablation with impedance monitoring safely and reliably produces
      electrically isolating, transmural Cox maze lesions in vivo.

PMID- 16305887
TI  - Ross operation in the young: a ten-year experience.
AB  - BACKGROUND: The Ross operation is an alternative to mechanical aortic valve
      replacement in the young. However, early and late complications after operation
      have been reported. In order to assess the role of the Ross operation in children
      and young adults, a 10-year clinical experience was reviewed. METHODS: Ninety
      male and 22 female patients, aged 29 +/- 10 years (range, 6-49) underwent cross
      sectional clinic and echocardiographic examination. Indication for Ross operation
      was aortic regurgitation in 79 patients, stenosis in 11, and mixed lesion in 22;
      82 (73%) had a bicuspid valve. Endpoints of the study were survival and freedom
      from autograft dilatation, from autograft and homograft dysfunction, and from
      reoperation. RESULTS: There was 1 (1%) hospital and 1 late (1%) death, during an
      average follow-up of 5.1 +/- 1.9 years (range, 0.1-10.6). At 10 years, survival
      was 98 +/- 2%. Late autograft dilatation was identified in 32 (29%) patients and
      regurgitation in 15 (14%), 7 of whom had autograft dilatation. Ten-year freedom
      from autograft dilatation was 43 +/- 8% and from regurgitation was 75 +/- 8%.
      Multivariate analysis showed younger age (p = 0.05), preoperative aortic root
      dilatation (p = 0.02), root replacement technique (p = 0.03), and absence of
      pericardial strip buttressing (p = 0.04) to be predictive of autograft
      dilatation. Eleven (10%) patients required reoperation on the autograft (8
      prosthetic valve replacement, 3 autograft root repair). Ten-year freedom from
      reoperation was 72 +/- 10% and from replacement of the autograft was 88 +/- 5%.
      Pulmonary homograft obstruction was identified in 6 (5%) patients, requiring
      homograft replacement in 1. All but 2 (2%) patients were in New York Heart
      Association class I, with a return to regular school grade or active employment.
      CONCLUSIONS: Late outcome for the Ross procedure is excellent in terms of
      survival and quality of life. Late root dilatation, autograft regurgitation, and
      homograft stenosis, however, show increasing prevalence with time. Technical
      modifications of the procedure, yearly aortic root imaging, and early
      reintervention on the dilated neoaortic root may further enhance the durability
      of the autologous pulmonary valve.

PMID- 16305888
TI  - Invited commentary.

PMID- 16305889
TI  - Current status of the European Association for Cardio-Thoracic Surgery and the
      Society of Thoracic Surgeons Congenital Heart Surgery Database.
AB  - BACKGROUND: After utilizing separate congenital databases in the early 1990s, the
      Society of Thoracic Surgeons (STS) and the European Association for Cardio
      Thoracic Surgery (EACTS) collaborated on several joint database initiatives.
      METHODS: In 1998, the joint EACTS-STS International Congenital Heart Surgery
      Nomenclature and Database Project Committee was created and a common nomenclature
      and common core minimum database dataset were adopted and published by the STS
      and the EACTS. In 1999, the joint EACTS-STS Aristotle Committee was created and
      the Aristotle Score was adopted and published as a method to provide complexity
      adjustment for congenital heart surgery. Collaborative efforts involving the
      EACTS and STS are underway to develop mechanisms to verify data completeness and
      accuracy. RESULTS: Since 1998, this nomenclature, database, and methodology of
      complexity adjustment have been used by both the STS and EACTS to analyze
      outcomes of over 40,000 patients. A huge amount of data have been generated which
      allow comparison of practice patterns and outcomes analysis between Europe and
      North America. The aggregate data from the first 5 years of data collection not
      only make for interesting comparison but also allow examination of regional
      difference in practice patterns. For example, in the EACTS, out of 4,273
      neonates, 885 (20.7%) underwent arterial switch procedures and 297 (6.95%)
      underwent Norwood stage 1 procedures. In the STS, out of 3,988 neonates, 472
      (11.8%) underwent arterial switch procedures and 575 (14.4%) underwent Norwood
      stage 1 procedures. CONCLUSIONS: This analysis of the EACTS-STS multi
      institutional outcomes database confirms that in both Europe and North America,
      case complexity and mortality is highest among neonates, then infants, and then
      children. Regional differences in practice patterns are demonstrated, with the
      overall goal being the continued upgrade in the quality of surgery for congenital
      heart disease worldwide.

PMID- 16305891
TI  - Invited commentary.

PMID- 16305890
TI  - Correction of tetralogy of Fallot and of pulmonary atresia with ventricular
      septal defect in adults.
AB  - BACKGROUND: Early correction is regarded as the treatment of choice for patients
      with tetralogy of Fallot or pulmonary atresia with ventricular septal defect.
      Nevertheless, some of these patients reach adulthood without early correction.
      This study sought to assess risk factors for operative mortality and determine
      the benefit of total correction in adolescent and adult patients. METHODS: A
      retrospective analysis of 52 patients (>16 years at the time of corrective
      surgery) for tetralogy of Fallot (n = 42) or pulmonary atresia with ventricular
      septal defect (n = 10) between 1974 and 2003 was performed. RESULTS: Age at
      correction was 28.9 +/- 9.9 (16 to 57 years). There were 8 early deaths (15.4%).
      Preoperative hemoglobin concentration (p = 0.002) and reconstruction of the right
      ventricular outflow tract with a patch (p = 0.002) were correlated with a
      significantly higher early mortality. Mean follow-up time was 12.3 +/- 10.4
      years. Late deaths (n = 6; 11.5%) were cardiac-related in 2 of 6 cases. At follow
      up, 28 patients (87.5%) were assigned to the New York Heart Association
      functional class I. Twenty-four patients led a normal life with full-time work, 6
      patients were able to do part-time work, and only 2 patients experienced
      noticeable limitation on activities. CONCLUSIONS: Repair of tetralogy of Fallot
      and of pulmonary atresia with ventricular septal defect in this patient group is
      associated with a high early mortality. Preoperative chronic cyanosis, expressed
      by elevated hemoglobin concentration, is predictive for early mortality. Because
      cyanosis has been shown to lead to multiorgan dysfunction, we conclude that
      preoperative multiorgan dysfunction may be the intrinsic risk factor for
      perioperative mortality. Surgical correction in this patient group should still
      be recommended because the functional status considerably improves.

PMID- 16305892
TI  - One and one-half ventricle repair: results and concerns.
AB  - BACKGROUND: The study was designed to assess the long-term results of one and one
      half ventricular repair on systemic and pulmonary circulation, right ventricular
      growth and function, and the prevalence of arrhythmias. METHODS: Eighty-four
      patients undergoing one and one-half ventricular repair between January 1990 and
      December 2003 were studied. Age was 4 to 504 months (mean, 47.9 +/- 57.3 months).
      Sixty-nine survivors underwent serial echocardiography, radionuclide studies,
      cardiac magnetic resonance imaging, and cardiac catheterization. RESULTS:
      Operative and late mortality were 10.7% and 8%, respectively. Perioperative and
      postoperative supraventricular arrhythmias were observed in 14.3% and 15.9% of
      patients, respectively. Risk factors for supraventricular arrhythmias included
      systemic ventricular dysfunction, heterotaxy syndrome, and Ebstein's anomaly.
      Mean late postoperative superior vena caval pressure was 14.2 +/- 1.52 mm Hg and
      right atrial pressure was 6.6 +/- 0.74 mm Hg. At a median follow-up of 87 months,
      actuarial survival was 81.9% +/- 0.04%, and 89.8% were in New York Heart
      Association class I or II. Serial cine-magnetic resonance imaging demonstrated
      significant growth of tricuspid valve and right ventricular cavity in 45% of
      patients. CONCLUSIONS: One and one-half ventricular repair can be performed with
      an acceptable risk. The operation maintains a low pressure in the inferior vena
      caval tributaries, and reverses the Fontan paradox. Patients with tripartite
      right ventricles demonstrated a tendency toward enlargement of the pulmonary
      ventricular chamber commensurable with somatic growth.

PMID- 16305893
TI  - Long-term results of apical aortic conduits in children with complex left
      ventricular outflow tract obstruction.
AB  - BACKGROUND: Apical aortic conduits were used in children with complex left
      ventricular outflow tract obstruction at our institution before we adopted the
      Ross and Ross-Konno procedures. The early results with apical aortic conduits
      were quite good when we used a porcine xenograft conduit and were less
      satisfactory when we converted to an aortic homograft valve as the conduit valve.
      This report summarizes our clinical experience with apical aortic conduits in
      children with an emphasis on hemodynamic results, reoperation, and long-term
      follow-up. METHODS: Records of 28 patients (age range, 2 weeks to 19 years) who
      underwent insertion of apical aortic conduit between September 1979 and June 1993
      were reviewed. All patients had complex multilevel left ventricular outflow tract
      obstruction. All were symptomatic, and 22 (79%) had had one or two previous
      aortic valvotomies or left ventricular outflow tract operations, or both.
      RESULTS: Hospital mortality was 11% (3 of 28). Twenty-five children survived the
      perioperative period and improved, and 21 have had one or more cardiac
      catheterization from 6 to 18 months (mean, 1.2 years) after the initial
      operation. Reduction or resolution of resting mean left ventricular-to-aortic
      peak gradient in the early postoperative period from 81.8 +/- 24.0 to 15.4 +/-
      8.9 mm Hg was demonstrated (p < 0.001). Overall 25-year survival was 57%.
      Fourteen surviving patients (56%) have undergone subsequent procedures (n = 18)
      from 5 months to 16 years postoperatively (mean, 6.9 years) because they
      developed a recurrent left ventricular-to-aortic gradient of 58 +/- 28 mm Hg (p <
      0.002). One patient underwent heart transplantation. All other late survivors
      have normal left ventricular function as determined by serial echocardiography.
      CONCLUSIONS: Apical aortic conduit is effective in relieving complex left
      ventricular outflow tract obstruction and improving left ventricular performance
      with acceptable short-term and midterm results, but late complications caused
      primarily by conduit tissue valve dysfunction are frequent in children. Since the
      early 1990s, the apical aortic conduit procedure has been largely replaced with
      the Ross or Ross-Konno procedure in our pediatric practice.

PMID- 16305894
TI  - Totally endoscopic robotic-assisted repair of patent ductus arteriosus and
      vascular ring in children.
AB  - BACKGROUND: This study reports on our initial experience with robotically
      assisted patent ductus arteriosus (PDA) closure and vascular ring division in
      children. METHODS: From April 2002 to May 2004, 15 patients underwent PDA closure
      (n = 9) and vascular ring repair (n = 6) by a totally endoscopic approach,
      utilizing the Da Vinci robotic system. The mean age of the patients was 8.3 +/-
      4.7 years (range, 3 to 18) and the mean weight, 35.5 +/- 19.0 kg (range, 14.1 to
      77.0 kg). Three thoracoscopic trocars were used to accommodate the endoscopic
      camera and two surgical instruments with an additional small incision for lung
      retraction. After dissection by the surgeon seated at the master console, PDA
      ligation with clips or division of the atretic arch and ductal ligament was
      performed. RESULTS: Total operative times were 170 +/- 46 minutes (PDA) and 167
      +/- 48 minutes (vascular ring). One patient with vascular ring was converted to
      thoracotomy because of dense adhesions due to previous surgery. Precise and easy
      surgical maneuver was possible with the articulated surgical instruments and
      three-dimensional visualization in 14 patients. Intraoperative transesophageal
      echocardiography confirmed no persistent shunt in all PDA patients. No laryngeal
      nerve injury and hemorrhage were noted. All patients were extubated in the
      operating room. Median length of postoperative hospital stay was 1.5 days.
      CONCLUSIONS: Robotically assisted PDA closure and vascular ring division is a
      feasible and safe procedure. Future technologic improvement, including smaller
      instrument size and incorporation of tactile feedback, may permit application of
      this technique to even younger infants and intracardiac repairs.

PMID- 16305895
TI  - Invited commentary.

PMID- 16305896
TI  - Pediatric poststernotomy mediastinitis.
AB  - BACKGROUND: Mediastinitis results in significant morbidity in pediatric cardiac
      patients. It is not clear whether delayed sternal closure is a risk factor for
      these infections. Management of mediastinitis remains controversial. METHODS:
      Cases of mediastinitis at the Stollery Children's Hospital from January 1, 1991,
      to June 30, 2004, were reviewed. RESULTS: There were 29 cases of mediastinitis in
      2,675 open cardiac procedures for an overall incidence of 1.1%. Infection was
      diagnosed 5 to 27 days after the original surgical procedure (median, 10 days).
      The odds ratio for infection with delayed sternal closure versus primary sternal
      closure was 1.88 (95% confidence interval, 0.63 to 5.60). Signs at the onset of
      infection included fever (86%), incisional erythema (69%), purulent drainage from
      the incision or pacer wire sites (83%), and wound dehiscence (23%). Debridement
      was followed by primary sternal closure in all but three cases in which the
      sternum had not been closed before debridement and rotational muscle flaps were
      not used. Continuous irrigation systems were used only in the first 7 patients.
      One patient died of mediastinitis complicated by infective endocarditis, and 2
      patients died of multiorgan failure. CONCLUSIONS: Delayed sternal closure was not
      a major risk factor for mediastinitis, especially if primary skin closure was
      used with delayed sternal closure. Excellent results were attained with
      debridement and primary closure of these infections.

PMID- 16305897
TI  - Free pericardial fat pads can act as sealant for preventing alveolar air leaks.
AB  - PURPOSE: This study was performed to investigate the safety and efficacy of a
      method using free pericardial fat pads as a sealant to prevent intraoperative and
      postoperative alveolar air leaks. DESCRIPTION: Animal experiments were performed.
      After pulmonary parenchymal defects were created in 4 dogs, the alveolar air
      leaks were sealed with free pericardial fat pads. Clinical application was
      applied in 23 patients who underwent pulmonary resection, air leaks with stream
      of bubbles, or worse, were sealed with free pericardial fat pads. EVALUATION: All
      dogs survived for 1 month without complications. At sacrifice, all treated lungs
      had expanded adequately and the implanted fats remained on the lung surface.
      Histologic examination showed that the excised edge of the lung was closed with
      granulation. The clinical outcome showed the mean duration of air leaks, chest
      drain, and postoperative hospitalization were 2.3 +/- 3.1 days, 4.3 +/- 3.2 days,
      and 11.1 +/- 3.7 days, respectively. Recurrent air leaks were not observed after
      removal of the chest tube. No adverse effects were observed after surgery.
      CONCLUSIONS: The use of free pericardial fat pads was able to successfully
      prevent alveolar air leaks.

PMID- 16305898
TI  - Invited commentary.

PMID- 16305899
TI  - Miniaturized cardiopulmonary bypass in coronary artery bypass surgery: marginal
      impact on inflammation and coagulation but loss of safety margins.
AB  - PURPOSE: Inflammation and coagulation disturbances are common consequences of
      cardiopulmonary bypass (CPB). Recently, miniaturized closed CPB circuits without
      cardiotomy suction and venous reservoir have been proposed to reduce complication
      rates. We compared outcomes with conventional (CCPB) and miniaturized
      cardiopulmonary bypass (MCPB) after coronary artery bypass operations (CABG) with
      respect to inflammation and coagulation. DESCRIPTION: Thirty patients (23%
      female; aged 67.9 +/- 9.0 years) were prospectively randomly assigned to undergo
      isolated CABG with CCPB or MCPB. Conventional CPB had a pump prime of 1, 600 mL.
      Miniaturized CPB consisted of a centrifugal pump, arterial filter, heparinized
      tubing, and oxygenator with a priming volume of 800 mL. Shed blood was removed by
      a cell-saving device and reinfused. Measurements included interleukin (IL)-2
      receptor, IL-6, IL-10, tumor necrosis factor receptor 55 and 75, C reactive
      protein, leukocyte differentiation, d-dimers, fibrinogen, and thrombocytes at six
      time points. EVALUATION: In both groups no major complication occurred. However,
      two dangerous air leaks occurred in the closed MCPB circuit, demonstrating the
      narrow safety margins. Operative handling was also more difficult owing to
      limitations in venting and fluid management. International normalized ratio (p =
      0.03) and antithrombin III (p = 0.04) levels were elevated during CPB in the CCPB
      group, most likely owing to differences of the intraoperative anticoagulation
      management. Repeated measures analysis revealed that not a single parameter of
      inflammation or clinical outcome showed significant differences among groups.
      CONCLUSIONS: Use of a MCPB affected inflammation and coagulation variables only
      marginally and did not lead to clinical relevant changes as assessed by blood
      loss, need for blood products, and intensive care unit and clinical stays.
      However, safety margins for volume loss, air emboli, and weaning from CPB
      decrease, because of the closed MCPB circuit.

PMID- 16305900
TI  - Invited commentary.

PMID- 16305901
TI  - Safety and efficacy of a novel gel for vascular occlusion in off-pump surgery.
AB  - PURPOSE: Coronary occlusion techniques used during off-pump coronary artery
      bypass surgery often provide suboptimal visualization and can damage the
      endothelium. We evaluated a novel gel with reverse thermosensitive properties for
      internal vessel occlusion during off-pump coronary artery bypass surgery.
      DESCRIPTION: Yorkshire pigs (n = 6 per group) underwent two cycles of mid-left
      anterior descending coronary artery (LAD) occlusion using the gel (injected into
      the artery) or microvascular clamps (control group) followed by 30 minutes of
      reperfusion. Regional wall motion and LAD flow were monitored, microvessel
      relaxation responses were evaluated, and myocardial tissue was analyzed
      histologically. EVALUATION: Complete left anterior descending coronary artery
      occlusion was successfully achieved using the gel (median ischemic time, 14
      minutes; range, 4.5 to 24 minutes). Anterior wall motion abnormalities as well as
      flow patterns in the reperfused left anterior descending coronary artery were
      similar in both groups. Microvessel relaxation to substance P was mildly impaired
      (-11.7 +/- 2.8% vs control; p < 0.001) in the left anterior descending coronary
      artery territory, but response to adenosine diphosphate and sodium nitroprusside
      was unaffected. Mild contraction band necrosis was present in both groups,
      consistent with mild ischemia-reperfusion injury. CONCLUSIONS: The gel represents
      a safe and effective method of vessel occlusion with a potentially important role
      in off-pump coronary artery bypass surgery.

PMID- 16305902
TI  - Invited commentary.

PMID- 16305903
TI  - Surgical revision after percutaneous mitral valve repair with a clip: initial
      multicenter experience.
AB  - PURPOSE: Almost 50,000 mitral valve operations are performed annually in the
      United States, with an increasing number of repairs. Recently, a percutaneous
      mitral valve repair option that achieves edge-to-edge approximation with a clip
      has been described in patients with mitral regurgitation. DESCRIPTION: We
      describe 6 patients from three centers with mitral regurgitation after
      percutaneous repair who underwent reintervention. During open surgical revision,
      the clips were uneventfully removed in all patients with no limitation in
      surgical options. Five patients underwent repair and 1 underwent replacement.
      EVALUATION: After surgical revision, mitral regurgitation was significantly
      decreased, and all but 1 patient underwent uneventful recovery. One patient
      developed ilio-femoral deep venous thrombosis that was treated successfully with
      anticoagulation. CONCLUSIONS: Preserving standard of care options is critical
      with any evolving technology in the event of initial treatment failure. Standard
      surgical options were preserved in all of the patients who underwent percutaneous
      mitral valve edge-to-edge repair. Furthermore, a thorough understanding of the
      clip design, in particular its unlocking mechanism, is essential and facilitates
      surgical clip removal.

PMID- 16305904
TI  - Hemoptysis and massive hemothorax as presentation of intralobar sequestration.
AB  - Intralobar sequestration is a rare abnormality usually diagnosed at later age
      after a history of recurrent pulmonary infections. We present a case of a 55-year
      old man in whom both hemoptysis and massive hemothorax were the initial
      presenting symptoms. This report shows that intralobar sequestration can have a
      dramatic course of disease, and for this reason resection of the sequestered
      tissue should be considered in all patients.

PMID- 16305905
TI  - Successful treatment for lung cancer associated with pulmonary sequestration.
AB  - We encountered a 69-year-old man with lung adenocarcinoma and pulmonary
      sequestration. The cancer lesion was located in the left upper lobe, with
      sequestration of the left lower lobe. Left upper lobectomy was performed after
      induction chemoradiotherapy, but the sequestered lung lobe was preserved because
      the preoperative respiratory function was poor. Preservation of the sequestered
      lung during surgery for lung cancer should be considered in patients who have
      poor respiratory function and no signs of respiratory infection.

PMID- 16305906
TI  - Endoscopic ultrasound-guided fine needle aspiration for diagnosis of recurrent
      nonsmall cell lung cancer.
AB  - Diagnosis of recurrent lung cancer by various imaging studies is often difficult
      because a recurrent tumor can resemble scar tissue or postoperative changes. This
      article reports how an endoscopic ultrasound-guided fine needle aspiration was
      used to obtain a tissue diagnosis of locoregional lung cancer recurrence, which
      changed the management of the patients.

PMID- 16305907
TI  - Urgent contralateral pneumonectomy after single lung transplantation for
      lymphangioleiomyomatosis.
AB  - Left single lung transplantation in a 33-year-old woman affected by end-stage
      lymphangioleiomyomatosis was complicated by spontaneous and diffuse bleeding from
      the right lung at the end of the procedure. The right lung was completely
      deteriorated and the only option to stop the bleeding was a right pneumonectomy.
      At 14 months after transplantation, the single allograft showed good lung
      function with acceptable volumes. Single lung transplant and contralateral
      pneumonectomy can be considered a safe procedure in case of complications related
      to native lung either in case of lymphangioleiomyomatosis than for other lung
      diseases (emphysema, cystic fibrosis).

PMID- 16305908
TI  - Pulmonary sclerosing hemangioma with metastasis to the mediastinal lymph node.
AB  - During a routine health care evaluation, an abnormal shadow was detected in the
      chest roentgenogram of a 35-year-old man. Chest computed tomography scanning
      showed a nodule, approximately 3 cm in diameter, in the left S6 pulmonary segment
      with surrounding infiltration. Bronchoscopy revealed obstruction of the left B6c
      bronchus by a tumor, for which biopsy was done but no definitive histologic
      diagnosis could be made. Then, left lower lobectomy was performed, and the tumor
      was diagnosed as a pulmonary sclerosing hemangioma. A mediastinal lymph node (no.
      7) showed some metastatic tumor cells. As lymph node metastasis from pulmonary
      sclerosing hemangioma is very rare, we herein report the details of our case.

PMID- 16305909
TI  - A giant endobronchial inflammatory polyp.
AB  - Bronchial inflammatory polyps are defined as tumor-like lesions. They are usually
      related to chronic inflammatory processes in the adult. Because they may cause
      complications, they should be surgically removed. A 55-year-old male patient had
      been followed for recurrent pulmonary infections for 40 years. His main symptoms
      were orthopnea and hemoptysis upon admission to our hospital. A chest
      computerized tomography (CT) revealed bronchiectasis located at the right middle
      lobe and lower lobe and obstruction of the main bronchus at the level of carina.
      In bronchoscopy a mobile polypoid pinkish lesion protruding to the trachea was
      observed. We performed an inferior bilobectomy. The pathological examination
      revealed an endobronchial fibroepithelial polyp. The presence of a giant
      endobronchial polyp with chronic respiratory symptoms over an extended period of
      time and the rarity of information pertaining to these lesions in the literature
      provoked intrigue and constituted a worthy presentation.

PMID- 16305910
TI  - Cold sensitivity as a new side effect after sympathicotomy for hyperhidrosis.
AB  - Extremity cold sensitivity is a previously unreported side effect of
      thoracoscopic sympathicotomy. We report a case of a young man who underwent
      thoracoscopic sympathicotomy for hyperhidrosis, after which cold sensitivity
      developed in his sympathicotomized right hand and arm. When exposed to cold, the
      right hand and forearm become numb and the skin temperature drops to
      uncomfortable levels, while the left extremity remains comfortably warm.

PMID- 16305911
TI  - Three cases of orthotopic heart transplantation for arrhythmogenic right
      ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiomyopathy that
      primarily affects the heart muscle in the right ventricle. The ventricular muscle
      is replaced by fatty or fibrous tissue in a diffuse or spotty process. We
      performed orthotopic heart transplantations in 3 patients and all patients are
      alive. When ARVC has progressed to heart failure in the right or left ventricles,
      orthotopic heart transplantation is an effective therapeutic option.

PMID- 16305912
TI  - Repair of right ventricular free wall defect with a de-epithelized pedicled
      myocutaneous latissimus dorsi muscle flap.
AB  - Rupture of the right ventricle may occur because of sternal dehiscence or
      mediastinitis after cardiac surgery. Direct suture, polytetrafluoroethylene
      patch, fasciae, and muscle flaps have been used to close a right ventricular
      rupture. A unique occurrence of repair of a full-thickness right ventricle defect
      with a de-epithelized myocutaneous flap is presented. Our patient experienced a
      rupture of the right ventricle complicating sternal wound infection. The rupture
      was reconstructed with a polytetrafluoroethylene patch, but the patch needed to
      be removed because of infection. The defect was reconstructed with a de
      epithelized myocutaneous latissimus dorsi flap. The patient indicated no signs of
      complication during follow-up.

PMID- 16305913
TI  - Traumatic aorto-right ventricular fistula with aortic insufficiency.
AB  - We present a case of a traumatic aorto-right ventricular fistula coexistent with
      aortic insufficiency due to perforation of the left coronary leaflet, which is a
      lesion rarely described in the literature. We compare our experience with reports
      from the literature.

PMID- 16305914
TI  - Saccular aneurysm of the aortic cusp associated with discrete subaortic stenosis.
AB  - A 54-year-old male who experienced a syncopal episode underwent aortic valve
      replacement for aortic stenosis and regurgitation. The aortic valve was
      incompetent as a result of thickening of the left coronary cusp and noncoronary
      cusp. In addition a saccular aneurysm was indicated on the left coronary cusp. A
      shelf of tissue protruding at right angles from the ventricular septum was
      particularly prominent below the right coronary cusp, resulting in subvalvular
      stenosis. The cause of the saccular aneurysm was most likely caused by the long
      term effects of the jet stream instigated by discrete subaortic stenosis.

PMID- 16305915
TI  - Coronary embolism and subsequent myocardial abscess complicating ventricular
      aneurysm and tachycardia.
AB  - A 62-year-old female experienced a ventricular aneurysm and tachycardia caused by
      coronary embolism from mitral valve endocarditis. The patient underwent
      endoventricular patch plasty and cryoablation concomitant with valve replacement
      and survived without any operative complications. Pathological examination
      suggested that abscess formation played an important role regarding the
      disruption of the ventricular wall and development of the ventricular aneurysm
      and tachycardia. In previous reports, a myocardial abscess caused by a septic
      embolism has only been diagnosed using postmortem examinations as colony growth
      around the capillary vessels in the myocardium. We considered that our operation
      was effective and feasible in such an occurrence.

PMID- 16305916
TI  - Mediastinal fibrosis causing myocardial ischemia.
AB  - This report describes an unusual etiology of coronary artery disease. A 60-year
      old male presented with angina. He was treated with methysergide for migraine. It
      was determined that the patient possessed an extremely thick-walled ascending
      aorta that caused the coronary ostial narrowing. He underwent replacement of the
      ascending aorta and proximal aortic arch. Double vessel coronary artery bypass
      grafting was performed using saphenous vein. Microscopic examination indicated
      the pathology to be sclerosing mediastinis.

PMID- 16305917
TI  - Myocardial ischemia caused by an abnormal origin and course of the left coronary
      artery in an adult.
AB  - An anomalous course of the left anterior descending artery is a rare but
      potentially fatal condition. We herein describe the treatment and management of a
      patient who was diagnosed with this ailment.

PMID- 16305918
TI  - Neurological monitoring and off-pump surgery in a very high-risk stroke patient.
AB  - Stroke remains a high risk of coronary artery bypass grafting. We present a
      patient with progressively symptomatic coronary disease and severe four-vessel
      cerebrovascular disease not amenable to revascularization. This patient underwent
      coronary revascularization without neurologic complication using off-pump
      coronary surgery to avoid aortic manipulation and intraoperative
      electroencephalographic monitoring of cerebral perfusion. This management
      strategy may reduce the stroke risk in similar patients.

PMID- 16305919
TI  - Expanding retrograde saphenous vein graft aneurysm treated with endovascular
      coiling.
AB  - Saphenous vein graft aneurysm is a potentially fatal complication of coronary
      artery bypass grafting and usually requires surgery. This report describes
      endovascular coiling of a saphenous vein graft aneurysm that developed after redo
      coronary artery bypass grafting. The aneurysm occurred in a proximally occluded
      saphenous vein graft after revascularization of the same target vessel. The
      procedure required a retrograde approach through a patent left internal mammary
      and left anterior descending artery to reach and successfully thrombose the
      aneurysm.

PMID- 16305920
TI  - Off-pump repair of a giant pseudoaneurysm of a distal saphenous vein bypass
      graft.
AB  - Pseudoaneurysm of a saphenous vein bypass graft is a rare occurrence after
      coronary artery bypass grafting but may have lethal consequences. We treated a
      giant pseudoaneurysm of a saphenous vein graft to the right coronary artery in an
      80-year-old male Jehovah's Witness who had undergone coronary artery bypass
      grafting 4 and a half years earlier. His history revealed a recurrent sternal
      wound infection. By using a venous patch to close the damaged graft, we were able
      to perform a successful surgical repair without the need for extracorporeal
      circulation.

PMID- 16305921
TI  - Tricuspid valve repair in an infant with multiple obstructive Candida mycetomas.
AB  - Neonatal fungal valve endocarditis is an uncommon and highly lethal disease. The
      ideal management strategy is still controversial. Current options include
      antifungal chemotherapy and surgical intervention, the latter being often limited
      by risks inherent with valve operations in low body weight infants. We present a
      case of a premature infant with multiple Candida tricuspid valve mycetomas.
      Eradication of infection was achieved by combined liposomal amphotericin therapy
      and complex tricuspid valve repair. Indications, technical aspects, and outcome
      of treatment in infants are reviewed.

PMID- 16305922
TI  - Neonatal right atrial aneurysm.

PMID- 16305923
TI  - Chronic traumatic aneurysm of the left main coronary artery causing myocardial
      infarction.

PMID- 16305924
TI  - A new technique of subcutaneous colon interposition.
AB  - A colon interposition graft may be placed in the subcutaneous position when other
      routes are not available. Creation of an adequate subcutaneous tunnel may be
      difficult, especially in patients with prior sternotomy. In this report we
      describe a method that utilizes tissue expanders to facilitate subcutaneous
      esophageal reconstruction.

PMID- 16305925
TI  - A new technique for T-tube insertion in tracheal stenosis located above the
      tracheal stoma.
AB  - Tracheal stenosis is one of the main complications of long-term intubation. The
      Montgomery T-tube is a safe way to treat patients with tracheal stenosis who are
      unable to undergo surgical procedures. We describe a simple and practical
      technique for the insertion of the T-tube in tracheal stenosis located above the
      tracheostomy, while maintaining ventilation throughout the whole procedure.

PMID- 16305926
TI  - Marsupialization of intramyocardial left anterior descending artery: a novel
      approach for easy access during revascularization.
AB  - The left anterior descending (LAD) artery is the most important vessel bypassed
      during coronary revascularization procedures. This artery usually runs a
      superficial course, making it easy for localization and grafting. However, many
      times it takes a course deep in the myocardium or is embedded in thick epicardial
      fat, which results in technical challenges to the surgeon for localization and
      grafting. So far, many techniques are described for overcoming these problems,
      but all require cardiopulmonary bypass (CPB), and in fact, intramyocardial LAD is
      considered a relative contraindication for off-pump coronary artery bypass
      grafting (OPCAB). In the present era of enhanced interest in OPCAB, these
      techniques are not as helpful as they are for conventional CABG with CPB. Here,
      we describe a novel approach of marsupialization of the LAD for revascularization
      of intramyocardial LAD that is useful for off-pump as well as conventional
      revascularization procedures and makes grafting simple and reproducible.

PMID- 16305927
TI  - Median sternotomy closure: a simple inexpensive effective technique.
AB  - A technique of median sternotomy closure that improves the usual rates of sternal
      infection, dehiscence, and re-exploration for hemorrhage is presented. This
      closure adds minimal time and expense to the case and diminishes the amount of
      blood loss and transfusion in the postoperative period.

PMID- 16305928
TI  - Autofluorescence bronchoscopy and endobronchial ultrasound: a practical review.
AB  - Endobronchial ultrasound (EBUS) and autofluorescence bronchoscopy (AFB) are the
      two technologies to have the largest impact on diagnostic bronchoscopy in the
      last forty years. The AFB utilizes inherent tissue properties to identify
      preinvasive lesions of the central airways. The EBUS can accurately define airway
      invasion versus compression from tumors, guide transbronchial needle aspiration
      of hilar and mediastinal lymph nodes, and predict, based on ultrasound
      morphology, whether peripheral nodules are benign or malignant. It is also
      extremely useful for determining the proximal and distal extent of tumors in and
      around the airway, and aid in surgical planning. This article will review the
      principles and clinical applications of these two technologies.

PMID- 16305929
TI  - Impact of intravenous magnesium on post-cardiothoracic surgery atrial
      fibrillation and length of hospital stay: a meta-analysis.
AB  - Postoperative atrial fibrillation can occur in 25% to 40% of patients undergoing
      cardiothoracic surgery. Although the majority of postoperative atrial
      fibrillation is benign, it has been associated with prolonged hospital length of
      stay. Magnesium prophylaxis against postoperative atrial fibrillation has been
      evaluated in several clinical trials; however these trials were small in size and
      therefore conveyed mixed or inconclusive results. In an attempt to better
      understand magnesium's role in this setting, we conducted a meta-analysis. A
      systematic literature search was conducted from January 1999 through August 2004
      to identify trials of prophylactic magnesium in the setting of cardiothoracic
      surgery. The primary outcome measure was the incidence of postoperative atrial
      fibrillation. Trials were further analyzed based on cumulative doses of magnesium
      and perioperative time of initiation of prophylaxis, as well as length of stay.
      Seven randomized trials were identified. Upon meta-analysis, magnesium was found
      to prevent postoperative atrial fibrillation with an odds ratio of 0.66 and 95%
      confidence interval of 0.51 to 0.87. The incidence of postoperative atrial
      fibrillation was also significantly reduced in the low dose with an odds ratio of
      0.36 and 95% confidence interval of 0.23 to 0.56, and in the preoperative groups
      with an odds ratio of 0.46 and 95% confidence interval of 0.31 to 0.67.
      Prophylactic magnesium reduced length of stay (n = 6 studies) by a weighted mean
      difference of 0.29 days, with a 95% confidence interval 0.54 to 0.05.
      Prophylactic magnesium reduced cardiothoracic surgery patients' risk of
      postoperative atrial fibrillation and length of stay. Administering lower doses
      and initiating prophylaxis in the preoperative period achieved the greatest
      reduction in postoperative atrial fibrillation.

PMID- 16305930
TI  - Does minimally invasive vein harvesting technique affect the quality of the
      conduit for coronary revascularization?
AB  - The effect of minimally invasive great saphenous vein harvest on patient
      morbidity (wound infection and other healing disturbances) has been extensively
      investigated, yet its impact on the quality of the venous conduit is less well
      known. This study aims to review the literature with regard to macroscopic
      quality, postoperative myocardial infarction rates, and angiographic patency of
      the minimally invasive versus conventionally harvested vein using meta-analytic
      techniques where appropriate. Results suggest that conduits are comparable in
      macroscopic quality with minimally invasively harvested veins requiring more
      repairs prior to grafting. Postoperative myocardial infarction rates were not
      significantly different between groups, which is supported by the limited
      evidence on angiographic patency.

PMID- 16305931
TI  - Transplantation at 100 years: Alexis Carrel, pioneer surgeon.

PMID- 16305933
TI  - Innovative single-stage repair of severe asymmetric pectus excavatum defects.

PMID- 16305934
TI  - Self-expandable metal stents for endobronchial pathology.

PMID- 16305935
TI  - Sleep deprivation and results in cardiac surgery: dangerous study with very
      dangerous conclusions.

PMID- 16305937
TI  - Longest time of support by the Novacor left ventricular assist device without
      pump exchange.

PMID- 16305938
TI  - Computed tomography scan in redo valvular surgery.

PMID- 16305939
TI  - Incidence of stroke following coronary surgery without cardiopulmonary bypass:
      does the avoidance of aortic manipulation make a difference?

PMID- 16305943
TI  - A clinical overview of pseudobulbar affect.

PMID- 16305944
TI  - The pathophysiology of emotional lability: many paths to a common destination.

PMID- 16305945
TI  - Therapeutic options for emotional lability: current and emerging treatments.

PMID- 16305946
TI  - Image guided tumour ablation.
AB  - Several different technologies have been employed for the local ablation of
      tissue by thermal techniques. At the present time the most widely favoured
      technique is radiofrequency ablation (RFA) but developments in other techniques,
      e.g. microwave may change this. In many countries RFA or percutaneous ethanol
      injection (PEI) are accepted therapies for patients with Childs Pugh Class A or B
      cirrhosis and early hepatocellular carcinoma (HCC). Results for RFA in large
      series of patients with liver metastases from colon cancer are very promising.
      Five-year survival rates of 26% from the time of first ablation and 30% from the
      diagnosis of liver metastases for patients with limited (<6, <5 cm) liver disease
      who are not surgical candidates compares well with post resection series where 5
      year survival rates vary between 29% and 39% in operable candidates. Sufficient
      experience has now been gained in lung and renal ablation to show that these are
      minimally invasive techniques which can produce effective tumour destruction with
      a limited morbidity. More novel areas for ablation such as adrenal or pelvic
      recurrence are being explored.

PMID- 16305947
TI  - Complications of percutaneous therapy.
AB  - Percutaneous tumour ablation is a minimally invasive, image guided procedure
      which attracts a low morbidity (2%-10%) and procedure-related deaths are
      exceptional. As such it can be offered to patients who could not withstand more
      invasive procedures such as surgical resection. Complications can be divided into
      systemic and local, those related to the anatomical area and those specific to
      the ablative technique or the particular tumour type. Most ablation experience
      has been gained using radiofrequency in the liver for metastases or
      hepatocellular carcinoma. Newer applications include ablation of inoperable lung
      primary or metastatic disease and renal cell carcinoma. The most common
      complications are haemorrhage, super-added infection or collateral damage. Tumour
      dissemination, whilst a theoretical risk, is very unusual.

PMID- 16305948
TI  - Communication between radiologists and patients with cancer.

PMID- 16305949
TI  - Neuroblastoma in childhood: review and radiological findings.
AB  - The natural history, biologic and histological features, and the presenting
      symptoms of neuroblastoma are reviewed. The radiological findings of this
      neurogenic paediatric tumour are discussed.

PMID- 16305950
TI  - Value of bilirubin oxidase and its mutants in the diagnosis of
      hyperbilirubinemia.
AB  - OBJECTIVE: To elucidate the significance of the coordination amino acid residues
      in bilirubin oxidase (BO) and their kinetic characteristics, and evaluate whether
      BO mutants may serve as better diagnostic agent for hyperbilirubinemia. METHODS:
      The BO mutants I402G and C457S were obtained by site-directed mutagenesis and
      confirmed by amino acid sequence analysis. Ru-incorporated C457S mutant was
      obtained by direct incubation of ruthenium compounds with the mutant. The
      electron paramagnetic resonance (EPR) spectra of the recombinant BO and the
      mutants were investigated, and the enzyme kinetics of the recombinant BO and
      I402G mutant were measured with bilirubin as the substrate at 25 degrees C.
      RESULTS: The BO mutants were expressed and purified successfully. The mutant
      I402G showed low enzyme activity, and had C457S virtually no enzyme activity.
      Nevertheless Ru-incorporation conferred higher enzyme activity to C457S mutant.
      The enzyme kinetic investigations revealed that the kinetic parameter k(cat) of
      the recombinant BO and I402G mutant was 235.8 min(-1) and 6.9 min(-1),
      respectively, suggesting higher enzyme activity of the recombinant BO.
      CONCLUSIONS: The coordinating amino acids have important significance in
      maintaining the integrity of active centers and enzyme activities of recombinant
      BO and its mutants. The enzyme activities of the mutants I402G and C457S are much
      lower than those of recombinant BO, therefore they are not appropriate for
      diagnostic purpose. Ru-incorporation facilitates the formation of a new intact
      active center in C457S mutant, which therefore acquires enzyme activity.

PMID- 16305951
TI  - Correlation of multidrug resistance with up-regulation of protein kinase C
      expression in KBV200 cells.
AB  - OBJECTIVE: To investigate protein kinase C (PKC) expression and its association
      with multidrug resistance (MDR) in KBV200 cells. METHODS: KBV200 cells were
      preincubated with PKC activator phorbol-12-myristate-13-acetate (PMA, 200 nmol/L)
      and PKC activity was assayed by measurement of peptide substrate (32)P
      incorporation from [gamma-(32)P]ATP, with the cells without PMA preincubation
      serving as the control. Western blotting was performed for assessing the
      expression of PKC isoform, and the cell inhibition rate was evaluated by MTT
      assay. RESULTS: PMA preincubation of the cells significantly enhanced the
      activity of the total PKC and the membrane fraction, but lowered the PKC activity
      of the cytosol fraction, as compared with the cells without PMA treatment
      (P<0.01). PKC-alpha expression was upregulated in the membrane fraction and down
      regulated in the cytosol fraction in KBV200 cells after PMA preincubation.
      PKCbeta expression was slightly elevated in the cytosol fraction but exhibited no
      obvious changes in the membrane fraction after PMA pretreatment of the cells. The
      values of IC(50) of vincristine and adriamycin in PMA-treated cells were
      increased to 2275.5 nmol/L and 233.25 nmol/L, respectively (P<0.01). CONCLUSION:
      PMA can increase the multidrug resistance of KBV200 cells, which suggests the
      possible involvement of PKC in the mechanism of multidrug resistance of tumor
      cells.

PMID- 16305952
TI  - [Construction and functional analysis of a novel eukaryotic expression plasmid of
      recombinant immunotoxin DT390-Rantes].
AB  - OBJECTIVE: To construct a novel eukaryotic expression plasmid for recombinant
      immunotoxin DT390-Rantes and perform preliminary analysis of its function.
      METHODS: The gene fragment coding for Rantes was obtained from the liver tissues
      of C57BL/6 mice using RT-PCR, and inserted into the eukaryotic expression plasmid
      SRalpha containing DT390 gene to construct the recombinant plasmid DT390-Rantes
      SRalpha, which was transformed into E. coli JM109, followed by selection of the
      positive clones containing the target inserts. The eukaryotic expression plasmid
      was analysed by PCR, restriction endonuclease digestion and DNA sequencing. The
      recombinance plasmid DT390-Rantes-SRalpha was transfected into NIH3T3 cells and
      its expression was observed by immunofluorescence detection. The activity of the
      expressed DT390-Rantes in vitro was evaluated by MTT assay. RESULTS: The gene
      fragment of Rantes was correctly inserted into the eukaryotic expression plasmid
      SRalpha as verified by restriction endonuclease digestion and DNA sequencing, and
      could be expressed in NIH3T3 cells. MTT assay confirmed that the expression
      product DT390-Rantes could kill activated T cells in vitro. CONCLUSIONS: The
      recombinant eukaryotic expression plasmid DT390-Rantes-SRalpha is successfully
      constructed and expressed in eukaryotic cells. The expressed product can
      specifically kill activated T cells in vitro.

PMID- 16305953
TI  - [Construction of eukaryotic expression vectors of two mutants of hypoxia
      inducible factor-1 and their expressions in human microvascular endothelial
      cells].
AB  - OBJECTIVE: To construct eukaryotic expression vectors of two mutants of hypoxia
      inducible factor-1 (HIF-1alpha) and study their expressions in human
      microvascular endothelial cells (HMVECs). METHODS: Site-directed mutagenesis was
      performed to induce the mutation of the codons for the residue Pro564 (ccc) in
      HIF-1alpha into gcc (Ala) in pcDNA3.1(+)-HIF-1alphato obtain single-site-mutated
      vector pcDNA3.1(+)-HIF-1alpha-564Ala, which was then subjected to a second site
      directed mutagenesis to convert the codons for Asn803 into that of Ala (gct) to
      acquire double-site-mutated pcDNA3.1(+)-HIF-1alpha-564Ala-803Ala. After
      lipofectin-mediated transient transformation of HMVECs with the 3 recombinant
      plasmids including the two plasmids containing the mutations and the one without
      mutation, respectively, the expression levels of HIF-1alpha mRNA and protein were
      determined using RT-PCR, immunofluorescent staining and Western blotting.
      RESULTS: DNA sequence analysis demonstrated success of the two-step mutagenesis
      and the two plasmids of pcDNA3.1+-HIF-1alpha-564Ala and pcDNA3.1(+)-HIF-1alpha
      564Ala- 803Ala were obtained, both of which could produce HIF-1alpha protein
      resistant to oxidation degradation in HMVECs as compared with the non-mutated
      one. CONCLUSION: The recombinant plasmids pcDNA3.1(+)-HIF-1alpha-564Ala and
      pcDNA3.1(+)-HIF-1alpha- 564Ala-803Ala have been successfully constructed with
      efficient expressions in HMVECs.

PMID- 16305954
TI  - [Construction and characterization of mutant Enteroaggregative E. coli O42 strain
      with high-pathogenicity island deletion].
AB  - OBJECTIVE: To construct and characterize a mutant Enteroaggregative E.
      coli(EAggEC) O42 strain with in-frame deletion of high-pathogenicity island
      (HPI). METHODS: The kanamycin resistance gene (kan) was inserted between the
      sequences of irp8 and irp5 genes as the two homologous sequences for construction
      of the recombinant plasmid pCO85 by subcloning the recombined sequence into the
      suicide vector pCVD442. By homologous recombination and conjunction mobilization,
      EAO85 mutant with deletion of the core region of HPI about 24 kb spanning from
      irp8 to irp5 sequences was screened. RESULTS: Irp8 and irp5 genes of EAggEC O42
      were exchanged by pCO85 by conjunction mobilization with the selection by
      sucrose. The EAO85 mutant was identified by their failure to yield PCR products
      with primers specific for the internal regions of HPI. CONCLUSION: We have
      successfully constructed a mutant of EAggEC O42 strain with HPI in-frame
      deletion, which may facilitate the exploration of the role of HPI in EAggEC
      strain.

PMID- 16305955
TI  - [Differentiation of neonatal rat striatal neural stem cells induced by all-trans
      retinoic acid].
AB  - OBJECTIVE: To investigate the role of all-trans retinoic acid (atRA) in inducing
      differentiation of neonatal rat striatal neural stem cells (NSCs). METHODS:
      Neonatal rat striatal NSCs were obtained by mechanical isolation and serum-free
      culture. The roles of atRA at different concentrations in inducing the
      differentiation of NSCs were observed by immunofluorescent cytochemical staining,
      and the expression of retinoic acid receptor (RAR) gene was determined by semi
      quantitative RT-PCR. RESULTS: atRA could dose-dependently accelerate the
      differentiation of NSCs into neuron-like cells, and the physiological
      concentration of atRA was optimal for inducing NSC differentiation. atRA could
      induce the expression of RARbeta mRNA in a dose- and time-dependent manner.
      CONCLUSION: atRA can accelerate differentiation of NSCs into neuron-likes cells
      and up-regulate the expression of RAR-beta mRNA in neonatal rat striatal NSCs.

PMID- 16305956
TI  - [Sequence analysis of the mutated genes in CTXEVC Phi and nct-CTXnew Phi genomes
      in Vibrio cholerae JS94484 strain].
AB  - OBJECTIVE: To analyze the sequences of the mutated genes in CTX(EVC)Phi and nct
      CTX(new)Phi genomes in Vibrio cholerae JS94484 strain. METHODS: The mutated genes
      in CTX(EVC)Phi and nct-CTX(new)Phi genome were obtained by PCR, sequenced and
      analyzed. RESULTS: ig1, rstR, ig2, and ctxAB genes in CTX(EVC)Phi genome of V.
      cholerae strain JS94484 were highly homologous with those of standard EVC strain
      N16961, while ig1, rstR and ig2 genes in nct-CTX(new)Phi genome of the strain
      JS94484 shared low homology with those of the other 3 biotypes of V. cholerae.
      Considerable difference was detected in the last 60 bp of zot genes between
      CTX(EVC)Phi and nct-CTX(new)Phi genomes, indicating possible difference in the
      amino sequences of the Zot proteins encoded by these two genes. The sequence of
      toxin-coregulated pilus A subunit gene (tcpA) of the strain JS94484 was identical
      with that of strain N16961. CONCLUSION: ig1, rstR and ig2 genes of nct
      CTX(new)Phigenome are of a novel type, and their functions await further
      investigation.

PMID- 16305957
TI  - [Expression of cathepsins B and L in early gestational decidua and chorionic
      villi].
AB  - OBJECTIVE: To study the expression of cathepsins B and L in first-trimester
      gestational decidua and chorionic villi. METHODS: The decidua and chorionic villi
      in the first trimester of gestation were obtained from 30 women undergoing
      induced abortion, 25 with spontaneous abortion, 10 with normal endometrium in
      secretory phase, and 15 with bydatidiform mole in whom the expression of
      cathepsins B and L was determined by immunohistochemistry. RESULTS: Positive
      staining for cathepsins B and L were mainly detected in the trophoblasts and
      decidual cells. The positive expression rate of cathepsin B in the normal
      endometrium of secretory phase, decidua in the first trimester of gestation and
      spontaneous abortion were 10% (1/10), 83.3% (25/30), and 32.0% (8/25),
      respectively, and the rate of cathepsin L expression in the endometrium in
      secretory phase, decidua of induced abortion and spontaneous abortion were 0.0%,
      63.3% (19/30), and 32.0% (8/25) respectively, showing significant difference in
      the expression rates of cathepsins B and L between the 3 groups (P<0.05). Strong
      positive expression of cathepsin B in chorionic villi of induced abortion,
      spontaneous abortion and hydatidiform mole were detected at the rates of 10.0%
      (3/30), 0.0%, and 66.7% (10/15), respectively, and cathepsin L at the rates of
      26.7% (8/30), 4.0% (1/25), and 80.0% (12/15), respectively, with significant
      difference in strong cathepsins B and L expressions between the 3 groups
      (P<0.05). CONCLUSION: The expression of cathepsins B and L differs in normal and
      abnormal deciduas and chorionic villi of early pregnancy, suggesting that the
      cathepsins may play important roles in the process of implantation.

PMID- 16305958
TI  - [Bone defect repair with a new tissue-engineered bone carrying bone morphogenetic
      protein in rabbits].
AB  - OBJECTIVE: To construct a new tissue-engineered bone with poly (D, L-lactide-co
      glycolide) (PLGA), bone morphogenetic protein (BMP) and bone marrow-derived stem
      cells (BMSCs) and observe its effect in repairing segmental bone defects.
      METHODS: A 15-mm bone defect in the right radius was induced in New Zealand white
      rabbits, and the models were randomized into three groups to receive implantation
      of the tissue-engineered bone grafts constructed with PLGA carrying 5 mg BMP and
      about 1 x 10(6) BMSCs (experimental group), grafts of PLGA with about 1 x 10(6)
      BMSCs (control group), or grafts of exclusive PLGA (blank control group),
      respectively. The osteogenesis in the bone defect after the implantation on was
      evaluated X-ray films, and the histological changes of the tissues sampled from
      the bone defect 4, 8, and 12 weeks after operation were observed and new bone
      formation was measured by image analysis. RESULTS: The bone defect was completely
      repaired in the experimental group 12 weeks after the implantation, showing the
      best results among the 3 groups. The bone defects in the blank control group was
      filled with only fibrous and connective tissues at 12 weeks. CONCLUSION: This
      tissue-engineered bone constructed with PLGA, BMP and BMSCs possesses good
      ability in repairing segmental bone defect.

PMID- 16305959
TI  - [Three-dimensional conformal hypofractionated radiotherapy for brain metastases
      of non-small-cell lung carcinoma: implications for whole brain irradiation].
AB  - OBJECTIVE: To evaluate the therapeutic effect of of whole brain irradiation (WBI)
      in the treatment of brain metastases of non-small-cell lung carcinoma and analyze
      the factors affecting the patients' survival. METHODS: Ninety-three cases of
      brain metastases of non-small-cell lung carcinoma receiving radiotherapy between
      January 1998 and February 2004 were retrospectively reviewed. Of these patients,
      68 were treated with three-dimensional conformal hypofractionated radiotherapy
      (3D-CRT) following WBI, while the other 25 underwent 3D-CRT alone. Kaplan-Meier
      method was used to analyze the survival rate and local control rate, and Cox
      proportional hazards model employed for determining prognostic factors
      influencing the patients' survival. RESULTS: The overall median actuarial
      survival of the patients was 14 months in the 3D-CRT+WBI group with 1- and 2-year
      actuarial survival rates of 50% and 27%, respectively, showing no significant
      difference from 3D-CRT group, which had a median survival of 11 months and 1- and
      2-year survival rates of 45% and 15% (P=0.502, log-rank test). Actuarial 1-year
      local control rate in 3D-CRT+WBI group was 90% as compared to 70% in 3D-CRT group
      (P=0.028, log-rank test). In multivariate analyses, active extracranial disease
      (P=0.002) and Karnofsky Performance Scale score (P=0.034) were identified as the
      independent prognostic factors for the patients' survival. CONCLUSION: WBI prior
      to 3D-CRT does not benefit the patients with brain metastases of non-small cell
      lung carcinoma for their survival, but may help improve the local control rate.

PMID- 16305960
TI  - [Construction of standard recombinant plasmids for 7 common mannan-binding lectin
      gene haplotypes].
AB  - OBJECTIVE: To construct the standard recombinant plasmids for 7 common haplotypes
      of mannan-binding lectin (MBL) gene. METHODS: The DNA samples with known
      haplotypes and genotypes of MBL gene were used as the templates for amplifying
      the fragments of MBL gene haplotypes including the promoter region and exon 1
      with sequence-specific primer-polymerase chain reaction (SSP-PCR) method. The
      amplified fragments were cloned into T vector and the bases located at codon 52
      and codon 57 of exon 1 in MBL gene were mutated respectively by site-directed
      mutagenesis. All the 7 recombinant plasmids were identified by PCR and direct
      sequence analysis. RESULTS: From the DNA samples with known haplotypes and
      genotypes of MBL gene, the standard plasmids of haplotypes HYPA, LXPA, LYQA, LYPA
      and LYPB of MBL gene were constructed by SSP-PCR and molecular cloning technique.
      From the recombinant plasmids of HYPA and LYQA, the standard plasmids of
      haplotypes HYPD and LYQC of MBL gene were constructed by site-directed
      mutagenesis, respectively. CONCLUSION: The constructed standard plasmids of
      haplotypes HYPA, LXPA, LYQA, LYPA, LYPB, HYPD and LYQC of MBL gene provide
      standard controls for detecting the SNPs, haplotypes and genotypes of MBL gene
      with such genotyping methods us SSP-PCR and real-time PCR.

PMID- 16305961
TI  - [Oxidative stress-induced differentiation of L6 myoblasts].
AB  - OBJECTIVE: To explore the relationship between the differentiation of L6
      myoblasts and oxidative stress. METHODS: MTT assay was used to determine the
      viability of L6 myoblasts, from which the total RNA was extracted for
      amplification of the myogenin gene fragment by RT-PCR. H(2)O(2)-induced
      morphological changes of the cells were observed. RESULTS: The myoblasts treated
      with low concentration of reactive oxygen (50 micromol/L H(2)O(2)) for 1 h
      exhibited accelerated cell growth (P<0.05), and treatment with 50 and 150
      micromol/L H(2)O(2) induced the gene expression of myogenin, a molecular marker
      for differentiation of myoblasts. Morphological study revealed myotube formation
      and accelerated differentiation of the myoblasts induced by H(2)O(2). CONCLUSION:
      The reactive oxygen may serve as the intracellular signal molecules to induce the
      growth and differentiation of the myoblasts.

PMID- 16305962
TI  - [Evaluation of quality of life of hypertensive patients].
AB  - OBJECTIVE: To evaluate the quality of life (QOL) of patients with hypertension.
      METHODS: Totally 319 patients with hypertension were investigated for their QOL
      in comparison with 319 healthy controls using the World Health Organization
      Quality of Life assessment instrument (WHOQOL-100). RESULTS: The scores of
      physical functions, psychological condition, independent ability, social
      relation, living environment, and personal faith and the total score of QOL-100
      were significantly lower in the hypertensive patients than in the normal subjects
      (P<0.01). After adjusting the confounding factors of other diseases, the scores
      of all the items with the exception of personal faith and the total score of QOL
      100 were all lower in the patients than in the controls (P<0.01). Hostelling T2
      test and multivariate analysis of variance showed significant differences in the
      QOL between the hypertensive patients and the controls in the 6 domains
      synthesized (P<0.01), further demonstrating lowered QOL of hypertensive patients
      in comparison with the healthy population. CONCLUSION: Improvement of the
      hypertensive patients' QOL in addition to effective blood pressure control is a
      basic target in clinical therapy of hypertension.

PMID- 16305963
TI  - [Analysis of ERG11 gene mutation in Candida albicans].
AB  - OBJECTIVE: To study the relationship between fluconazole (FCZ)-resistance of
      Candida albicans and the mutation of ERG11 gene encoding FCZ-targeted enzyme.
      METHOD: Three strains of FCZ-susceptible and 10 FCZ-resistent C. albicans were
      isolated from the urethra, vagina, oropharynx, respiratory tract, prostate
      secretion and blood samples. ERG11 gene was amplified by PCR using C.albicans
      genomic DNA extracts as the templates and the DNA sequences of the PCR products
      were determined and compared using BLAST and Clustal-W softwares. RESULTS: The
      comparison of ERG11 gene sequences identified mutations at 21 sites in 13
      strains, including 17 same-sense and 4 missense mutations. Base substitutions at
      the sites of 348 bp and 383 bp resulting in D116E and K128T conversion may take
      place in both drug-resistant and drug-susceptible strains. The point mutation at
      the site of 1309 bp of FCZ-resistant strain may cause V437I change, and the base
      inversion at 1320 bp may give rise to A/C heterozygosity mutant of ERG11 gene,
      probably resulting in N440K conversion. CONCLUSION: FCZ-resistance of C. albicans
      may be associated with point mutations of V437I and N440K in ERG11 gene, but not
      with the point mutations of D166E and K128T.

PMID- 16305964
TI  - [Preparation and identification of monoclonal antibodies against different
      epitopes on human zeta globin chain].
AB  - OBJECTIVE: To prepare and identify the monoclonal antibodies (mAb) against human
      zeta globin chain. METHODS: BALB/c mice were immunized with purified recombinant
      zeta globin chain, and the hybridomas were generated by fusion of mouse spleen
      cells and myeloma cells NS-1. After three fusions and successive cloning, 3
      hybridoma cell lines secreting the mAb against zeta were obtained and the
      antibodies were purified from the ascites, followed by identification with
      indirect enzyme-linked immunosorbent assay (ELISA) and sandwich ELISA in
      combination with rabbit anti-zeta serum. RESULTS AND CONCLUSION: Three hybridoma
      cell lines secreting anti-zeta mAb were established, designated as 1A12, 3H9 and
      4D11, respectively. Both of 3H9 and 4D11 mAbs belonged to IgG1 isotype and mAb
      1A12 to IgG2a. All the mAbs could bind specifically to recombinant zeta and
      natural zeta globin from hemolysate of --(SEA) gene carrier. In addition, 1A12
      and 3H9 mAbs could recognize different epitopes on zeta globin, suggesting the
      possibility of developing a detection system for screening alpha-thalassemia with
      these mAbs.

PMID- 16305965
TI  - [Preparation of forsythiaside from Forsythia suspensa by high-performance liquid
      chromato- graphy].
AB  - OBJECTIVE: To prepare forsythiaside from Forsythia suspensa by high-performance
      liquid chromatography (HPLC). METHOD: A crude extract of Forsythia suspensa was
      prepared by water extraction and alcohol precipitation prior to polyamide column
      chromatography. Forsythiaside was prepared from the crude extract by RP-HPLC.
      RESULTS: Analysis with HPLC showed that the purity of the prepared forsythiaside
      reached 98%. CONCLUSION: HPLC is simple and effective for the preparation of
      forsythiaside from Forsythia suspensa.

PMID- 16305966
TI  - [Expression of L-type calcium channel alpha1C subunit in adult rat heart].
AB  - OBJECTIVE: To investigate the expression and distribution of L-type calcium
      channel alpha1C subunits in adult rat heart. METHODS: HE staining was applied on
      the frozen sections of adult rat heart to identify the sinoatrial node (SAN),
      atrioventricular node (AVN), and posterior nodal extension (PNE). The protein
      expression of L-type calcium channel alpha1C in adult rat heart and its cellular
      localization were examined by Western blotting and immunohistochemistry,
      respectively. RESULTS: L-type calcium channel alpha1C subunit was immunolocalized
      on the membrane of the myocardial cells, and its expression increased gradually
      in the SAN, AVN, PNE, right atrium and right ventricle. The protein level of L
      type calcium channel alpha1C in the AVN was similar to that in the PNE (P>0.05),
      and its level in the right atrium and ventricle were significantly higher than
      those in the SAN and AVN (P<0.01). The results of Western blotting were well
      consistent with the results of immunohistochemistry. CONCLUSION: The expression
      of L-type calcium channel alpha1C subunit may play a role in the
      electrophysiological functions of the heart.

PMID- 16305967
TI  - [Effects of needling in Baihui (DU20), Shuigou (DU26) and Shenmen (HT7) on
      glucose metabolism in the lentiform nucleus in patients with vascular dementia].
AB  - OBJECTIVE: To observe the effect of needling in Baihui (DU20), Shuigou (DU26) and
      Shenmen (HT7) on glucose metabolism in the lentiform nucleus in patients with
      vascular dementia. METHODS: Ten patients with vascular dementia were randomized
      equally into control group to receive the treatment of needling in the routine
      acupoints for hemiplegia (chosen from 6 Yang meridians of hand and foot) and
      treatment group with needling in 3 additional acupoints of Baihui (DU20), Shuigou
      (DU26) and Shenmen (HT7) for dementia. All the patients were examined by positron
      emission tomography (PET) to detect glucose metabolism in the bilateral lentiform
      nuclei before and after treatment. RESULTS: Glucose metabolism in the lentiform
      nucleus in normal lateral brain was obviously enhanced in the treatment group,
      but not in the bilateral lentiform nuclei in the control group after treatment.
      CONCLUSION: The effect of needling in Baihui (DU20), Shuigou (DU26) and Shenmen
      (HT7) for treatment of vascular dementia may involve the enhancement of glucose
      metabolism in the lentiform nucleus.

PMID- 16305968
TI  - [Effect of interferon alpha on liver fibrosis in patients with chronic hepatitis
      B].
AB  - OBJECTIVE: To observe the histological changes in the fibrotic and inflammatory
      tissues in response to interferon alpha treatment in patients with chronic viral
      hepatitis B. METHODS: Sixteen patients with chronic viral hepatitis B in S3-S4
      stages established by pathological examination were treated with interferon alpha
      for 6-9 months, and the degree of liver fibrosis and inflammation were examined 3
      times during the treatment. The expression of Fas, transforming growth factor
      beta1 (TGFbeta1) and HBcAg in the liver tissues were detected by
      immunohistochemistry, and DNA fragmentation was examined by TUNEL assay. The
      levels of the serum markers for liver fibrosis and liver function were also
      measured. RESULTS: Patients with liver fibrosis in S3-S4 stages had high
      pathological expression of Fas and TGFbeta1 with severe DNA damage in the liver
      tissues. After 3 months of interferon therapy, the expression of Fas and TGFbeta1
      were lowered (P<0.05), and further treatment till 3-9 months resulted in gradual
      decrease in the degree of hepatic fibrosis and cell apoptosis (P<0.05), with
      improved serum liver fibrosis indices and liver function. CONCLUSION: Interferon
      alpha may alleviate liver fibrosis and suppress cell apoptosis in patients in S3
      S4 stages after a 6- to 9-month continuous treatment.

PMID- 16305969
TI  - [Role of complement C3 in delayed-type hypersensitivity].
AB  - OBJECTIVE: To explore the role of complement C3 in delayed-type hypersensitivity
      (DTH). METHODS: After inducing DTH reaction in the footpads of C3 knockout C3(-/
      ) and wild-type (C3(+/+) ) mice with ovalbumin (OVA), the thickness of the
      footpad was measured and HE and immunohistochemical staining preformed to
      identify the number and types of the infiltrating mononuclear cells in the
      footpad tissues. T lymphocytes were separated from the spleens of the mice and
      incubated in 96-well plates with serial dilutions of OVA or mitogens in the
      presence of mitomycin C-treated macrophages, and the proliferation of the T cells
      was assessed by (3)H-TdR incorporation assay. RESULTS: The footpad thickness of
      DTH-C3(-/-) mice was significantly smaller than that of DTH-C3(+/+) mice. The
      number of the infiltrating mononuclear cells in the footpad tissue of C3(-/-)
      mice was obviously decreased in comparison with that of C3(+/+) mice, and the
      cells were characterized mainly as CD4(+) T lymphocytes. No significant
      difference in the proliferation of mitogen-stimulated splenic T cells was noted
      between C3(-/-) and C3(+/+) mice, but after stimulation with the specific antigen
      OVA, significant reduction in the proliferation of splenic T cells from C3(-/-)
      mice was observed as compared with the T cell proliferation in C3(+/+) mice.
      CONCLUSION: C3 defect results in impaired DTH responses in mice, which indicates
      the important role of C3 in DTH reaction.

PMID- 16305970
TI  - [Application of restorative laminoplasty combined with spinous process osteotomy
      and internal fixation for treatment of degenerative scoliosis].
AB  - OBJECTIVE: For treatment of mild degenerative scoliosis (DS) complicated with
      lumbar canal stenosis (LCS), posterior decompression and the spinal canal
      enlargement with spinous process osteotomy was performed in combination with
      fusion and pedicle screw instrument fixation. METHODS: Between 1999 and 2003, 18
      male and 26 female elderly patients (with mean age of 63 years, ranging from 47
      to 72 years) with DS complicated with LCS were treated with the described
      surgical procedures, including 25 with single segment lesion and 19 with
      involvement of 2 segments. A posterior medical incision from one vertebra
      superior to the target fusion area till the vertebral segment below it was made
      for spinal exposure. Undermining enlargement of the spinal canal was carried out
      according to the segments of the stenosis; in some cases the intervertebral disc
      was resected. Osteotomy was subsequently performed at the base of the spinous
      process, and the bony defect was covered with the spinous processes. Finally Moe
      fusion and Isola (17 cases) or Diapason (27 cases) instrument fixation were
      performed. The therapeutic effects were evaluated according to Oswestry scores
      and postoperative imaging examinations. RESULTS: The average follow-up period was
      3 years, ranging from 1 to 4 years. Thirty-three patients were followed up for
      one year and 93.9% of them had excellent or good outcome; 27 patients were
      followed up of 2 years and showed a rate for excellent or good results of 88.9%.
      Both sagittal and transverse diameters of the lumbar spinal canal were increased
      obviously as found by CT scanning without spinal canal scar. A rate of 92.6% of
      the ostetomized spinous processes had bony fusions. Successful covering bone
      healing was achieved in a mean of 4 months after surgery. Compressive vertebral
      fractures superior to the fixed segments occurred in 2 cases, including 1 with
      pedicle screw loosening and the other with pedicle screw breakage. Another
      patient had delayed wound healing. No recurrence of LCS, spondylolisthesis and
      decompensation, or pseudarthrosis of the spine was observed in these cases.
      CONCLUSION: The described surgical procedures for DS can decrease the occurrence
      of spinal canal scar and promote the healing of the covering bone, and can be a
      satisfactory treatment for mild DS complicated with LCS in the lumbar sagittal
      curve.

PMID- 16305972
TI  - [Prognostic factors for brain metastatic tumors treated with stereotactic
      radiosurgery].
AB  - OBJECTIVE: To assess the clinical outcome of brain metastatic tumors treated with
      linac-based stereotactic radiosurgery (SRS) and evaluate the potential prognostic
      factors. METHODS: We reviewed 102 patients with 131 brain metastatic tumors
      treated with a linac-based SRS from 1994 to 2002, including 78 patients with
      solitary and 24 with multiple brain metastases, with the diameter of tumor all
      within 4 cm. Among these 102 patients, 18 received planned whole-brain radiation
      therapy (WBRT) before or after SRS. Ninety-three patients with 120 lesions were
      evaluated for local tumor control analysis with follow-up imaging data. The
      patients' survival and local control of the tumors were estimated using Kaplan
      Meier method, and the potential prognostic factors were analyzed with univariate
      and multivariate analysis. RESULTS: The overall local tumor control rate and the
      actuarial local tumor control rate at 1 year were 92.5% and 87.6%, respectively.
      The tumor volume was the single significant predictor for local tumor control
      (P=0.035). The median survival of the 102 patients was 11 months. In univariate
      analysis, patients aged over 60 years (P=0.038) with KPS score above 70
      (P=0.001), absence of extracranial metastases (P=0.031) and administration of
      planned WBRT (P=0.025) were significant factors for survival. After adjustment of
      multivariate analysis, only KPS score was identified as the independent predictor
      (P=0.033). CONCLUSION: SRS is an effective method for treatment of brain
      metastases, and multiple factors may affect the local tumor control and survival
      of the patients.

PMID- 16305971
TI  - [Expression of lysophosphatidic acid receptor in human ovarian cancer cell lines
      3AO, SKOV3, OVCAR3 and its significance].
AB  - OBJECTIVE: To investigate the expressions of lysophosphatidic acid (LPA)
      receptors at both mRNA and protein levels and their biological significance in
      different human ovarian cancer cell lines. METHODS: Reverse transcription
      polymerase chain reaction (RT-PCR), streptovidin peroxidase-conjugated (SP)
      immunohistochemical assay and Western blotting were employed to measure the
      expression levels of LPA(1), LPA(2) and LPA(3) mRNA and LPA(2) and LPA(3) protein
      in cultured human ovarian cancer cell lines 3AO.SKOV3, and OVCAR3. RESULTS: All
      the ovarian cancer cell lines expressed LPA(1), LPA(2) and LPA(3) mRNAs and
      LPA(2) and LPA(3) proteins. CONCLUSION: LPA(1), LPA(2) and LPA(3) expressions
      occur extensively in human epithelial ovarian cancer cell lines, and LPA(2) and
      LPA(3) may be involved in the development and progression of human ovarian
      cancer.

PMID- 16305973
TI  - [Clinical analysis of 1,400 cases of coronary artery angiography without
      heparin].
AB  - OBJECTIVE: To evaluate the feasibility and safety of coronary artery angiography
      via femoral artery approach without heparin. METHODS: Totally 1 400 consecutive
      patients undergoing coronary artery angiography with heparin were analyzed
      retrospectively in comparison with the data of 354 patients for coronary artery
      angiography without heparin. RESULTS: Success in selective coronary artery
      angiography was achieved in 99.3% of the patients in the non-heparin group, with
      the mean operation time of 17.9+/-11.3 min ranging from 8 min to 1 hour.
      Angiography identified coronary artery stenosis in 72.2% of the patients
      including 49.8% with multivessel involvement. Subcutaneous hematoma occurred in
      25 (1.8%) of the patients, and 1 (0.07%) patient developed arterial and venous
      fistula and pseudoaneurysm at the puncture site, but other complications
      (retroperitoneal hematoma, acute myocardial infarction, stroke and peripheral
      artery thrombotic events) occurred neither during nor after the procedure. In the
      heparin group, 18 (5.1%) patients developed subcutaneous hematoma and 1 (0.2%)
      had arterial and venous fistula and pseudoaneurysm at the puncture site after
      angiography. CONCLUSION: Coronary artery angiography without heparin is both safe
      and feasible with only very low risk of complications.

PMID- 16305974
TI  - [Effects of local carbon ion irradiation on survival and peripheral blood
      leukocyte and platelet counts of tumor-bearing mice].
AB  - OBJECTIVE: To investigate the effects of local carbon ion irradiation on the
      length of survival and peripheral blood leukocyte and platelet counts of mice
      inoculated with pulmonary tumor cells. METHODS: Thirty tumor-bearing mice were
      randomly divided into control group (tumor-bearing but without carbon ion
      irradiation, n=10), 12 Gy group (n=10) and 24 Gy group (n=10). The right hind
      limbs of the mice, where the tumor cells were inoculated, were irradiated with
      carbon-ion beams at a single dose in 12 Gy and 24 Gy groups, and those of the
      control group received no irradiation. The peripheral blood leukocytes and
      platelets of the mice in all the 3 groups were counted immediately before and 7
      and 14 days after irradiation, respectively, with the survival time of the mice
      recorded. RESULTS: There was no significant difference in the survival time of
      the mice between the 3 groups. The peripheral blood leukocyte counts in all
      groups increased after irradiation, no significant difference was noted between
      the two irradiation the groups and the control group. Irradiation at 24 Gy
      resulted in significant increase in peripheral blood platelet count on the 14th
      day (P=0.032, F=4.062), but no such increment was observed in the other 2 groups
      or on day 7 in the 24 Gy group. CONCLUSION: Local carbon ion irradiation may not
      produce significant effects on the length of survival and hemogram of the tumor
      bearing mice.

PMID- 16305975
TI  - [Correlation of serum calcium level with tumor size and stage of renal cell
      carcinoma].
AB  - OBJECTIVE: To analyze the correlation between serum calcium level and tumor size/
      stage in patients with renal cell carcinoma (RCC). METHODS: Totally 173 RCC cases
      were divided into 3 groups according to their serum calcium level, namely low,
      normal and high level groups. SPSS10.0 software was used for statistical analysis
      of the tumor sizes/stages and their association with serum calcium level in the 3
      groups. RESULTS AND CONCLUSION: Kruskal-Wallis H test revealed no significant
      difference in the tumor size between the 3 groups (X(2)=4.768, df=2, P=0.092),
      but Spearman correlation analysis suggested inverse correlation between serum
      calcium and tumor size (r=-0.166, P=0.029). Kruskal-Wallis H test also failed to
      suggest significant difference in the tumor stage between the 3 groups
      (X(2)=4.277, df=2, P=0.118), but serum calcium was found to be inversely
      correlated with the tumor stage (r=-0.157, P=0.039 by Spearman correlation
      analysis).

PMID- 16305976
TI  - [Application of double-filtration plasmapheresis in major ABO-incompatible
      unrelated bone marrow transplantation].
AB  - OBJECTIVE: To evaluate the effect of double-filtration plasmapheresis (DFPP) in
      major ABO-incompatible unrelated allogenic bone marrow transplantation. METHODS:
      The red cell antibodies were removed by DFPP in 5 recipients to prevent hemolysis
      and pure red cell aplasia following major ABO-incompatible unrelated bone marrow
      transplantation. RESULTS: The isohemagglutinin titers of the 5 recipients were
      below 1:16 after DFPP with only one recipient developed transient mild acute
      hemolysis. Delayed hemolysis and pure red cell aplasia occurred in none of the
      cases and all recipients were completely engrafted. CONCLUSION: DFPP can
      effectively prevent hemolysis and pure red cell aplasia in recipients of
      unrelated bone marrow transplantation with major ABO-incompatibility.

PMID- 16305977
TI  - [Effects of benazepril combined with valsartan on congestive heart failure].
AB  - OBJECTIVE: To observe the effects of routine doses of benazepril combined with
      valsartan on congestive heart failure. METHODS: Totally 203 patients with
      congestive heart failure were randomized into Group A (receiving benazepril 20
      mg/day), Group B (benazepril,10 mg/day plus valsartan, 80 mg/day), and group C
      (valsartan 160 mg/day) for different treatment protocols on the basis of routine
      therapy for heart failure with digitalis, diuretics and beta blockers. The
      cardiac functions and echocardiographical findings were evaluated before and
      after the treatments. RESULTS: All the patients showed improvement of NYHA class,
      left ventricular end-diastolic dimension (LVEDd), left ventricular end-systolic
      dimension (LVESd) and left ventricular ejection fraction (LVEF) (P<0.01), and the
      effect was better in group B than in group A (P>0.05), and both groups A and B
      had better results than group C (P<0.05). No serious adverse effects were found.
      CONCLUSION: The combination of benazepril and valsartan at routine doses can be
      effective for treating congestive heart failure.

PMID- 16305978
TI  - [Effects of short-term chemotherapy on the compliance of rabbit abdominal aorta].
AB  - OBJECTIVE: To investigate the effect of short-term chemotherapy on the compliance
      of rabbit abdominal aorta, and understand the changes in the biomechanical
      properties of the blood vessels after chemotherapy. METHODS: Fifteen rabbits were
      divided into 5 groups, 4 of which were subjected to injection with
      chemotherapeutic agents for 5 days to evaluate the compliance of the abdominal
      aorta at 2, 7, 14, and 21 days after the therapy with the other group without
      chemotherapy serving as the control. RESULTS: The compliance of the abdominal
      aorta was obviously decreased after chemotherapy and reached the lowest level 14
      days after short-term chemotherapy, suggesting that the drugs resulted in
      vascular injury enough to alter the biomechanical properties of the blood
      vessels. CONCLUSION: Short-term chemotherapy can decrease the compliance of the
      blood vessels, which may deteriorate with time but such changes can be
      reversible.

PMID- 16305979
TI  - [Clinical analysis of early stage thrombolytic therapy with venous urokinase for
      acute myocardial infarction in 24 cases].
AB  - OBJECTIVE: To observe the therapeutic effect of early stage thrombolytic therapy
      with venous urokinase for acute myocardial infarction (AMI). METHOD: The clinic
      data of 24 patients treated with early stage thrombolytic therapy with venous
      urokinase and 18 conventional therapy were reviewed, and the repatency of the
      coronary artery and T-wave inversion within 24 h after the treatment were
      evaluated. RESULT: The repatency rate of urokinase group and conventional therapy
      group was 62.5% and 15.0%, respectively, showing significant difference (P<0.05).
      Shorter delay of administration of thrombolytic therapy after infarction onset
      resulted in higher rate of repatency. CONCLUSION: Early stage thrombolytic
      therapy with venous urokinase can improve the therapeutic effect and reduce the
      mortality rate of AMI, and is therefore recommended for clinical application.

PMID- 16305980
TI  - [Management of urinary obstruction following renal transplantation: report of 16
      cases].
AB  - OBJECTIVE: To explore the diagnosis and treatment of urinary obstruction
      involving the transplanted kidney. METHODS: A retrospective analysis was
      performed in 16 cases of urinary obstruction involving the transplanted kidney,
      including 5 cases of ureteral calculi, 6 vesicoureteral anastomotic stricture, 2
      pyeloureteral junction stricture after transplantation, 1 ureter necrosis due to
      graft rejection, and 2 infection surrounding the renal graft and ureter end
      necrosis. RESULTS: Only one patient had the renal graft removed due to massive
      hemorrhage in an open surgery for correction of urinary obstruction, and the
      renal function of the graft was preserved in all the other cases after endoscopic
      or open surgeries. In the follow-up for 0.5 to 3 years after the second surgery,
      serum creatinine of the patients were maintained within the range of 90-150
      micromol/L, without further renal enlargement or exacerbation of renal retention
      shown by B-mode ultrasonography. CONCLUSION: Urinary obstruction after renal
      transplantation is a difficult surgical complication, which can be managed by
      endoscopic or open surgeries depending on the causes of the obstruction.

PMID- 16305981
TI  - [Investigation of medical journal website construction in Guangdong province].
AB  - OBJECTIVE: To investigate the current status of internet-based publication of
      biomedical journals and website construction in Guangdong province. METHODS: On
      the platform of the currently available databases for academic science journals
      (Wanfang Datebase, China Acdemic Journal Network, PubMed and SCI) with the
      assistance general searching engines, the websites of the medical journals in
      Guangdong province were evaluated and the editorial offices of the core medical
      journals in Guangdong province were interviewed. RESULTS: At present, the
      internet-based publication of the journals was executed predominantly by 3 means,
      namely utilization of the access to the websites of the direct sponsor,
      authoritative websites of science and technology, or independent websites.
      CONCLUSION: Relying on the database system of Wanfang and China Academic Journal
      Network, for instance, most of the journals can provide access to their full-text
      resources, but this internet-based publication is somehow delayed in comparison
      with the print publication. At present, only a few medical journals in Guangdong
      have built their independent websites, and among those which already have,
      Journal of First Military Medical University and Cancer are indexed by IM and
      PubMed, therefore they provide online abstracts of the papers ahead of the print
      copy publication.

PMID- 16305982
TI  - Same-day pegfilgrastim and chemotherapy.
AB  - Pegylated filgrastim is a new formulation of a neutrophil colony-stimulating
      factor that has a long circulating half-life, permitting a single dose of
      filgrastim per cycle of chemotherapy. The pegylated filgrastim is recommended to
      be administered not less than 24 hours following chemotherapy and not less than
      14 days prior to chemotherapy based on the theoretic concern that marrow
      suppression would be accentuated. This schedule of usage for pegylated filgrastim
      may compromise its application for weekly chemotherapy schedules. We have treated
      80 patients with pegylated filgrastim administered on the same day as
      chemotherapy; the latter delivered on a weekly schedule. Twenty-four patients had
      non-small cell lung cancer (NSCLC) and were treated with one of two weekly
      chemotherapy regimens alternating triplets [AT] taxane, cisplatin, irinotecan
      alternating with gemcitabine, cisplatin, vinorelbine or alternating doublets [AD]
      taxane, cisplatin alternating with gemcitabine, vinorelbine; four of these
      patients also received weekly taxane and carboplatin with concomitant thoracic
      radiation. A consistent pattern emerged in which leukocytosis was observed at Day
      8; median WBC 15,800/uL (range 7,200 to 35,000/uL); at Day 14, the median WBC was
      9,300/uL (range 1,100 to 17,400/uL). Pegylated filgrastim can be given safely
      simultaneously with chemotherapy in weekly chemotherapy schedules. The
      pegfilgrastim can be administered on an every two week (fortnightly) schedule to
      maintain a weekly chemotherapy schedule.

PMID- 16305983
TI  - Procollagen alpha 1 type 1: a potential aide in histopathological grading of
      glioma.
AB  - Collagen type I production has been shown to play a role in malignant
      transformation. We examined procollagen type I expression in brain tumors and
      with histopathological grading. Expression levels of procollagen alpha 1 type 1
      were determined in 5 glioma cell lines by RT-PCR, Northern, and Western blot
      analysis. In addition, 41 primary brain tumors and 2 metastatic lung cancers to
      the brain were examined by PCR. Of the 5 glioma cell line analyzed, 3 (glioma 1,
      SW-1783 and U-118) expressed procollagen alpha 1 type I and were sensitive to
      vitamin D3 (VD3). In contrast, 2 of the cell lines (U-373 and T-98G) lacked
      procollagen alpha 1 type 1 expression. In patients' samples, 14 of 15 anaplastic
      and low grade gliomas expressed procollagen alpha 1 type I, and 12 of the 14
      expressed high levels. In contrast, only 12 of 21 high grade gliomas from
      patients expressed procollagen alpha 1 type1 and among these, only 4 of the 12
      expressed high levels. Thus, there is an inversed correlation between procollagen
      alpha 1 type 1 expression and histopathological grading (R2=- 0.56, p=0.0005).
      Our data suggest that procollagen alpha 1 type I expression occurs more commonly
      in intermediate and low grade gliomas and may assist in histopathological
      grading.

PMID- 16305984
TI  - How often should a port-A-cath be flushed?
AB  - While it is important during treatment to flush the port-A-cath (PAC) with
      heparin regularly, catheter maintenance needs to be evaluated in those patients
      who, after completion of therapy, retained their ports for extended periods of
      time. The manufacturer has recommended monthly accession to maintain catheter
      patency and function. Our objective is to demonstrate that a longer interval
      between maintenance accessions of PACs still may be medically safe, convenient,
      and more efficient. We performed a retrospective review of all patients who had
      undergone PAC insertion from 1988 to 1993 at the Albert Einstein College of
      Medicine, and from 1997 to 2002 at the New York Hospital Medical Center of
      Queens. An adequate maintenance time is defined as a period of at least 6 months
      without chemotherapy or total parenteral nutrition. Data collected included date
      and location of PAC insertion, date of PAC accessions, PAC complications, and
      results of attempts at flushing the catheters with no venous blood return. All
      data were entered into an Excel spreadsheet and analyzed. The difference in
      interval accessions in patients without any complication to patients with
      complication was calculated using the Mann-Whitney "U" test. A total of 73
      patients were included in the study. Compliance with visits for PAC maintenance
      varied considerably with the individual median accession times varying between 28
      and 262 days with an overall median of 42 days. The individual means ranged from
      29.5 to 244 days with an overall mean of 53.6 days. Seven patients in the group
      had episodes where the provider was unable to draw blood from the port during
      routine accession. The average intervals between accessions for each of these
      patients ranged from 38 to 244 days. The average intervals of accession among
      those patients who had no blood return during PAC accession was 79 days, versus
      63 days for those without any difficulty. The difference was not statistically
      significant (p>0.05). Monthly maintenance of PAC is excessive, inconvenient for
      the patients, and expensive. Extending the interval of PAC maintenance proves to
      be medically safe and beneficial to the patients, the physicians and the health
      care system. Our clinical experience suggests that less frequent accessions of
      PACs is safe and feasible. We strongly advocate future prospective investigation
      of alternative PAC maintenance protocols in gynecologic cancer patients.

PMID- 16305985
TI  - The activation of ERK1/2 via a tyrosine kinase pathway attenuates trail-induced
      apoptosis in HeLa cells.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) serves as an
      extracellular signal that triggers apoptosis in tumor cells. To characterize the
      molecular events involved in TRAIL-induced apoptotic signaling, we investigated
      the role of extracellular signal-regulated kinase 1/2 (ERK1/2) in HeLa cell
      death. Here we show that TRAIL-activated ERK1/2 through a tyrosine kinase
      dependent pathway, subsequently elevated anti-apoptotic Bcl-2 protein levels.
      ERK1/2 inhibition with PD98059 promoted apoptotic cell death through the
      downregulation of ERK1/2 activity and Bcl-2 protein levels. Moreover, tyrosine
      kinase inhibition with Genistein in TRAIL-induced apoptosis effectively
      attenuated ERK1/2 activity and enhanced apoptotic cell death. Taken together, our
      results indicate that ERK1/2 activation via tyrosine kinase pathway plays a
      protective role as the cellular defense mechanism through the upregulation of Bcl
      2 protein levels in TRAIL-induced apoptosis.

PMID- 16305986
TI  - Orbital MALT lymphoma in a patient with Graves' ophthalmopathy: a unique
      observation.
AB  - A 57-year-old woman with a six-year history of Graves' Disease with
      ophthalmopathy developed unilateral periorbital swelling. CT scan suggested a
      lacrimal mass. Biopsy revealed MALT lymphoma. Evaluation for other sites of
      lymphoma revealed no other evidence of disease. She was treated with radiation
      therapy only with complete disappearance of disease. This is the first known case
      of MALT lymphoma arising in Graves' ophthalmopathy.

PMID- 16305987
TI  - Myelopathy after radiation therapy and chemotherapy with capecitabine and
      gemcitabine.
AB  - This article describes a woman with metastatic upper gastrointestinal cancer who
      developed thoracic myelopathy unexpectedly after standard dosage and
      fractionation radiotherapy. She also was receiving capecitabine and gemcitabine
      concomitantly. There are few reported cases of chemotherapy potentiation of
      spinal cord radiation toxicity. These agents are known radiosensitizers, making
      it likely that they contributed to this adverse outcome. As these agents are
      increasingly incorporated into clinical trials of combined therapy, caution will
      be necessary in both trial design and clinical management.

PMID- 16305989
TI  - Through the looking glass at early-life exposures and breast cancer risk.
AB  - The global increase in the proportion of women diagnosed with breast cancer,
      inadequate access to screening and high cost of treatment for breast cancer argue
      strongly for a greater focus on preventive strategies. But at what age is it
      appropriate to begin targeting preventive approaches? The recognized role of
      perinatal nutrition in neurologic development and the relation of maternal
      nutritional status to birthweight and subsequent risk of hypertension, diabetes,
      and cardiovascular disease identify pregnancy and early childhood as potential
      phases for prevention. This review examines indicators of hormonal and
      nutritional exposures in early life and breast cancer risk through the lens of
      the life course paradigm integrated with maternal and child health research and
      methodology. Compared to women who were normal birthweight (2500-3999 g), women
      who weighed>or=4,000 g at birth have a 20 percent to 5-fold increased risk of
      premenopausal breast cancer. Women born preterm and likely to be small- or large
      for-date also have an increased risk. Birth length is directly associated with
      risk and has a larger magnitude of effect than birthweight. Prior preeclamptics
      and their daughters have a lower risk of breast cancer than comparable
      normotensives. An association between infant feeding practices and breast cancer
      is unclear without improved exposure assessment and analysis. Rapid childhood and
      pubertal linear growth increases breast cancer risk, while greater body fat over
      the same periods reduces risk. Growth data thus far have not been calculated in Z
      scores from reference growth curves for comparison across studies. Events and
      secular trends influencing birth cohorts may not be adequately addressed, thereby
      limiting the interpretation and implications of the findings. Research in
      nonhuman primates may help uncover underlying mechanisms.

PMID- 16305990
TI  - Immunomodulatory drugs.
AB  - After nearly decades of extinction as a sedative and antiemetic, thalidomide
      reemerged as the parent compound of a novel and promising class of therapeutics
      termed the immunomodulatory drugs (IMiDs). The analogues of thalidomide, CC-5013
      (lenalidomide, Revlimid) and CC-4047 (Actimid) are more potent regulators of
      cellular immune and cytokine response while lacking some of the dose limiting
      side effects of the parent compound, such as neurologic toxicity. Preclinical
      data will be reviewed that outlines these drugs' effects on tumor necrosis alpha,
      interleukin 12, angiogenesis, and T-cell function. The evolution of the use of
      thalidomide as a therapeutic for diseases such as multiple myeloma and
      myelodysplastic syndrome and the promising initial results of the new IMiDs will
      be reviewed.

PMID- 16305988
TI  - Nucleolar adaptation in human cancer.
AB  - While the nucleolus was first observed over two hundred years ago, its role in
      human cancers is only now being appreciated. Long thought to be a static,
      ribosome-producing, subnuclear organelle, recent investigations have shown a more
      dynamic and adaptable side of the nucleolus. Containing not only proteins for the
      production of ribosomes but also newfound nucleolar oncogenes and tumor
      suppressors, mechanistic links between the nucleolus and cancer are now more
      evident. In this regard, much of the work from the past decade has focused on the
      ability of these proteins to promote and suppress tumorigenesis from the
      nucleolus. In this review, we will discuss how historical measurements of the
      nucleolus are being translated into contemporary studies of nucleolar dysfunction
      in human cancer.

PMID- 16305991
TI  - Histone deacetylase inhibitors: a review of their clinical status as
      antineoplastic agents.
AB  - The histone code refers to specific modifications in the biochemical composition
      of nucleosome-associated histone proteins involved in the regulation of gene
      transcription. These modifications include, among several, acetylation,
      methylation, and phosphorylation of several histone amino acid residues and are
      associated with different states of chromatin configuration and gene expression.
      In particular, acetylation of specific residues in histones H3 and H4 has been
      associated with an open chromatin configuration and a permissive gene
      transcription state. This particular modification is regulated by several
      enzymatic activities with the capacity to either transfer acetyl groups or to
      induce histone deacetylation. This last activity is associated with gene
      silencing. Several agents have been shown to have histone deacetylase inhibitory
      activity (HDACI). In vitro, experiments in multiple neoplastic cancer cell lines
      have demonstrated that treatment with HDACIs results in increased global and gene
      specific histone acetylation, and reactivation of aberrantly silenced genes. This
      phenomenon has been associated with cell differentiation and induction of
      apoptosis. Based on these observations, several of these agents are now in
      clinical development both for solid tumor and hematological malignancies. In this
      article, we provide a brief introduction to the field of histone deacetylation
      inhibition in cancer and review the most relevant clinical data so far published.

PMID- 16305992
TI  - Ribonucleases as a novel pro-apoptotic anticancer strategy: review of the
      preclinical and clinical data for ranpirnase.
AB  - Cytotoxic ribonucleases (RNases), such as ranpiranase, represent a novel
      mechanism-based approach to anticancer therapy. These relatively small proteins
      selectively attack malignant cells, triggering apoptotic response and inhibiting
      protein synthesis. Ranpirnase, originally isolated from oocytes of Rana pipiens,
      is a member of a family of endoribonucleases. The anticancer effects of
      ranpiranase have been documented in both in vitro and in vivo experimental tumor
      models. The effects of ranpiranase appear to be selective for cancer cells. Based
      on Phase I study data, the maximum tolerated dose (MTD) was 960 microg/m2, with
      the dose-limiting toxicity (DLT) characterized by proteinuria with or without
      azotemia, peripheral edema, and fatigue. Ranpirnase did not induce
      myelosuppression, mucositis, alopecia, cardiotoxicity, coagulopathy,
      hepatotoxicity, or adverse metabolic effects. Phase II tumor-specific trials
      investigated the activity of ranpirnase in malignant mesothelioma, breast cancer,
      non-small cell lung cancer, and renal cell cancer. A Phase III randomized study
      in malignant mesothelioma patients compares the combination of ranpirnase plus
      doxorubicin to doxorubicin monotherapy.

PMID- 16305993
TI  - TRAIL: Activation of ERK1/2 Protects Cells Against Apoptosis.

PMID- 16305994
TI  - The Terri Schiavo case in Jewish law.

PMID- 16305995
TI  - Coelenterazine (marine bioluminescent substrate): a source of inspiration for the
      discovery of novel antioxidants.
AB  - Coelenterazine and derivatives were initially considered in the scientific
      community for their (bio)luminescent properties. Now, another interest of such
      hetero-bicycles has been pointed out by the discovery of remarkable antioxidative
      properties, and an unique mode of action as a "cascade": the mother-compound
      (imidazolopyrazinone) is transformed by ROS into a daughter-compound (2-amino
      pyrazine) also endowed with antioxidative properties. This review illustrates the
      therapeutic potential of synthetic imidazolopyrazinones (coelenterazine
      analogues): chemical reactivity assays with singulet oxygen, radical anion
      superoxide, peroxynitrite, and radicals formed during lipid and LDL peroxidation,
      cellular tests of protection against oxidative stress using keratinocyte,
      hepatocyte, neuronal and erythrocyte cells, and finally in vivo evaluation in a
      hamster model of ischemia-reperfusion, are fully described.

PMID- 16305996
TI  - Preparation and evaluation of floating risedronate sodium-Gelucire 43/01
      formulations.
AB  - Single and multi-unit floating matrices of risedronate sodium were prepared using
      Gelucire 43/01 by melt solidification and melt granulation technique,
      respectively. The controlled release floating matrices were evaluated for in
      vitro and in vivo floating ability and in vitro drug release. Effect of aging on
      Gelucire 43/01 was evaluated by hot stage microscopy (HSM), scanning electron
      microscopy (SEM), differential scanning calorimetry (DSC), in vitro floating
      ability, and in vitro drug release. Multi-unit system obtained has shown initial
      burst release, which was suppressed in single unit system. Both single- as well
      as multi-unit systems showed increase in rate of drug release on aging due to
      changes in the properties of the Gelucire 43/01. Multi-unit matrices obtained by
      melt granulation were relatively easier for scale up and advantageous if the
      initial burst release does not cause any significant clinical adversity.

PMID- 16305997
TI  - Identification of photoproducts of hexahydroquinoline derivatives by GC-EI-MS and
      HPLC-ESI-MS.
AB  - Photoproducts of hexahydroquinoline derivatives have been analyzed with gas
      chromatography electro ionization-mass spectrometry (GC-EI-MS) and high
      performance chromatography electrospray ionization-mass spectrometry (HPLC-ESI
      MS). The study was performed on four HHQ derivatives: 2,6,6-trimethyl-3
      carbomethoxy-5-oxo-4-(R-phenyl)-1,4,5,6,7,8-hexahydroquinoline; R=2'-Me, 3'-Me,
      2'-MeO, and 3'-MeO. The photochemical degradation of each of the HHQ derivatives
      led to the appearance of one product. The photoproducts were identified as the
      corresponding tetrahydroquinoline analogues, which were formed by dehydrogenation
      of dihydropyridine moiety. In GC-mass spectra, the most frequent way of
      fragmentation was elimination of CH3* or CH3O* radical of the ester group. In the
      photoproducts substituted at 2'-position of the phenyl ring, elimination of
      isobutene (C4H8) was observed. In the photoproducts with 3'-position
      substituents, elimination of COOCH3* radical was noted.

PMID- 16305998
TI  - In vitro release studies on matrix type transdermal drug delivery systems of
      naltrexone and its acetyl prodrug.
AB  - Matrix type acrylic adhesive transdermal patches of naltrexone (NTX) and its 3-O
      acetyl ester prodrug were prepared and evaluated for drug content, thickness, and
      in vitro release characteristics. Among the four DURO-TAK adhesive polymers (87
      2516, 87-2054, 87-2501, and 87-2582) tested, 87-2516 proved to be the most
      suitable and compatible polymer for the transdermal delivery of NTX from NTX and
      prodrug patches. A linear relationship was observed for release flux (F) and
      cumulative amount (Mt) values versus 1%, 2%, and 3% drug loading at equimolar
      levels. The release of NTX from the patches showed a good correlation (R2>0.99)
      for Mt vs. square root t profiles, indicating that a Higuchian matrix diffusion
      mechanism of drug release from the transdermal adhesive patches was obtained.
      Overall, the amounts of NTX released from the prodrug patches were significantly
      higher than from the NTX patches, at all three drug loading levels.

PMID- 16305999
TI  - Reactivity of valganciclovir in aqueous solution.
AB  - The rates of hydrolysis of valganciclovir to ganciclovir and L-valine and
      isomerization of the R and S diastereomers of valganciclovir in aqueous buffer
      solution from pH 3.8 to 11.5 were determined at 37 degrees C. The kinetics of
      hydrolysis were first order for at least two half-lives in neutral and basic
      solutions. In acidic solutions where less than 10% degradation occurred, the rate
      of hydrolysis was determined assuming a first-order loss in drug. At 37 degrees C
      and pH 7.08, the half life is 11 h. The maximum stability at the pH values
      studied occurred at pH 3.81 with a half life of 220 days. The kinetics of the
      approach to equilibrium for the isomerization were first order and the ratio of
      the R:S isomer at equilibrium was 52:48. Isomerization was approximately 10 fold
      faster than hydrolysis over the pH range studied with a half-life at pH 7.01 of 1
      h. The maximum stability toward isomerization (t1/2>533 h) occurs at a pH below
      3.8. The pH-rate profile for the hydrolysis and the isomerization reaction are
      best described by hydroxide ion catalyzed mechanisms. In acidic and neutral
      solutions, the hydroxide reacts with the protonated form of the drug, while in
      basic solutions, the hydroxide reacts with the neutral form of the drug.

PMID- 16306000
TI  - Viscoelastic properties of a new in situ gelling thiolated chitosan conjugate.
AB  - The aim of this study was the synthesis of a new thiolated chitosan conjugate and
      the evaluation of its viscoelastic properties in vitro. The modification of
      chitosan was achieved by covalent attachment of isopropyl-S-acetylthioacetimidate
      to chitosan. The resulting conjugate (chitosan-TEA; chitosan-thioethylamidine)
      exhibited 300.7+/-27.4 micromol thiol groups per gram polymer and no disulfide
      bond. For rheological studies, the pH of 0.5% and 1% polymer solutions was
      adjusted to 6.5 in order to simulate a physiological pH-level. Both, 0.5% and 1%
      chitosan-TEA solutions showed the transition from sol to gel within 30 min.
      Within 6 h of incubation, the storage modulus of 0.5% and 1% chitosan-TEA
      increased 3354-fold and 6199-fold, whereas the loss modulus increased 11-fold and
      38-fold, respectively. Frequency sweep measurements demonstrated an increase in
      crosslinking of the thiolated polymer as a function of time. The formation of
      inter- and/or intramolecular disulfide bonds was monitored indirectly via
      determining the decrease of thiol groups. Unmodified chitosan did not exhibit in
      situ gelling properties. The release of a fluorescent marker being incorporated
      in a 0.5% chitosan-TEA solution was significantly (p<0.001) slower, when the
      formulation was preincubated for one hour and consequently already highly
      crosslinked. The polymer generated within this study represents a promising novel
      tool for various drug delivery systems, where in situ gelling properties are
      advantageous.

PMID- 16306001
TI  - Physico-chemical characterization and stability study of glassy simvastatin.
AB  - The objective of the present study was to investigate the glass forming
      capability of a model drug simvastatin. The glassy material produced by melt
      quench technique was subjected to physico-chemical characterization and
      subsequent stability and enthalpy relaxation study. The chemical stability of
      drug during preparation of glass was tested by High Performance Liquid
      Chromatography (HPLC) and Infrared (IR) spectroscopy. The presence of amorphous
      form was confirmed by DSC and XRPD. Surprisingly, glassy simvastatin was almost
      stable throughout the period of stability, inspite of its Tg being relatively
      low. The stability and very low enthalpy recovery of glassy simvastatin perhaps
      could be attributed to strong inter-molecular hydrogen bonding.

PMID- 16306002
TI  - The effects of competitive displacement on haloperidol's plasma distribution in
      normolipidemic and hyperlipidemic plasma.
AB  - PURPOSE: To assess whether dyslipidemia affects haloperidol's overall plasma
      distribution when it is in the presence of another highly protein bound drug that
      competes for plasma protein binding sites. METHODS: We performed in vitro studies
      in which warfarin sodium was pre-incubated in normolipidemic and hyperlipidemic
      plasma samples in varying concentrations. Following the pre-incubation with
      warfarin, [3H]-haloperidol mixed with unlabeled haloperidol was added to the
      plasma samples. The plasma was separated into its lipoprotein and lipoprotein
      deficient fractions by density gradient ultracentrifugation and haloperidol
      distribution was determined. RESULTS: Our results indicate that when
      normolipidemic plasma was pre-incubated with various concentrations of warfarin
      no significant redistribution of haloperidol was noted among the various plasma
      lipoprotein fractions. However, in the case of the hyperlipidemic plasma, pre
      incubating with warfarin did result in a significant redistribution of
      haloperidol from the lipoprotein-deficient fraction to the very-low-density and
      low-density fractions of lipoproteins. CONCLUSION: Understanding how plasma
      lipoproteins influence competitive displacement interactions would be valuable in
      helping to explain and perhaps predict pharmacokinetic parameters that may affect
      clinical outcome. The clinical significance of competitive displacement of drugs
      in patients with dyslipidemia requires further study.

PMID- 16306003
TI  - Content analysis and stability evaluation of selected commercial preparations of
      St. John's wort.
AB  - Content analysis and stability studies were performed for the commercial products
      of St. John's wort. Six marketed formulations were analyzed for their hypericin
      and pseudohypericin content. These products were standardized to contain 0.3%
      hypericin. Results revealed total hypericin as 7.72-38.57% of the labeled claim
      with varying concentrations of pseudohypericin. Stability studies were carried
      out under three different storage conditions: 1) 25+/-2 degrees C, 60+/-5%RH for
      six months, 2) 40+/-2 degrees C, 75+/-5%RH for six months, and 3) 50 degrees C
      for one month. Tablet formulations were also analyzed for their hardness and
      friability. Stability studies revealed significant decrease in the content of the
      marker compounds with time.

PMID- 16306004
TI  - Dissolution and solubility behavior of fenofibrate in sodium lauryl sulfate
      solutions.
AB  - The solubility of fenofibrate in pH 6.8 McIlvaine buffers containing varying
      concentrations of sodium lauryl sulfate was determined. The dissolution behavior
      of fenofibrate was also examined in the same solutions with rotating disk
      experiments. It was observed that the enhancement in intrinsic dissolution rate
      was approximately 500-fold and the enhancement in solubility was approximately
      2000-fold in a pH 6.8 buffer containing 2% (w/v) sodium lauryl sulfate compared
      to that in buffer alone. The micellar solubilization equilibrium coefficient (k*)
      was estimated from the solubility data and found to be 30884+/-213 L/mol. The
      diffusivity for the free solute, 7.15x10(-6) cm2/s, was calculated using
      Schroeder's additive molal volume estimates and Hayduk-Laurie correlation. The
      diffusivity of the drug-loaded micelle, estimated from the experimental
      solubility and dissolution data and the calculated value for free solute
      diffusivity, was 0.86x10(-6) cm2/s. Thus, the much lower enhancement in
      dissolution of fenofibrate compared to its enhancement in solubility in
      surfactant solutions appears to be consistent with the contribution to the total
      transport due to enhanced micellar solubilization as well as a large decrease
      (approximately 8-fold) in the diffusivity of the drug-loaded micelle.

PMID- 16306005
TI  - Influence of process variable and physicochemical properties on the granulation
      mechanism of mannitol in a fluid bed top spray granulator.
AB  - This study investigated the influence of specific process variables, including
      the hydroxypropyl cellulose (HPC) binder solution atomization, on the fluidized
      bed top spray granulation of mannitol. Special attention was given to the
      relationship between wetting and the granule growth profile. The atomization of
      the HPC binder solution using a binary nozzle arrangement produced droplets of
      decreasing size as the atomization pressure was increased, while changes in the
      spray rate had little effect on the mean droplet size. Increasing the HPC binder
      concentration from 2 to 8% w/w increased the binder droplet size and was most
      likely attributed to higher solution viscosity. The top spray granulation of
      mannitol showed induction type growth behavior. Process conditions like high
      spray rate, low fluidizing air velocity and binder solution concentration that
      promote the availability of HPC binder solution at the surface of the particles
      appeared to be key in enhancing nucleation and growth of the granules. Increasing
      the bed moisture level, up to a certain value, reduced the contribution of
      attrition to the overall growth profile of the granule and, more significantly,
      produced less granule breakage on drying. It was observed that the mean granule
      size could be reduced as much as 40% between the end of granulation and the end
      of drying for lower initial bed moisture level despite a shorter drying phase.
      High atomization pressure, especially when maintained during the drying phase,
      contributed substantially to granule breakage.

PMID- 16306006
TI  - Prediction of permeability coefficients of compounds through caco-2 cell
      monolayer using artificial neural network analysis.
AB  - Artificial neural network (ANN) analysis was used to predict the permeability of
      selected compounds through Caco-2 cell monolayers. Previously reported models,
      which were shown to be useful in the prediction of permeability values, use many
      structural parameters. More complex equations have also been proposed using both
      linear and non-linear relationships, including ANN analysis and various
      structural parameters. But proposed models still need to be developed using
      different neuron patterns for more precise predictions and a better understanding
      of which factors affect the permeation. To develop a simple and useful model or
      method for easy prediction is also a general need. Permeability coefficients (log
      kp) were obtained from various literature sources. Some structural parameters
      were calculated using computer programs. Multiple linear regression analysis
      (MLRA) was used to predict Caco-2 cell permeability for the set of 50 compounds
      (r2=0.403). A successful ANN model was developed, and the ANN produced log kp
      values that correlated well with the experimental ones (r2=0.952). The
      permeability of a compound, famotidine, which has not previously been studied,
      through the Caco-2 cell monolayer was investigated, and its permeability
      coefficient determined. It was then possible to compare the experimental data
      with that predicted using the trained ANN with previously determined Caco-2 cell
      permeability values and structural parameters of compounds. The model was also
      tested using literature values. The developed and described ANN model in this
      publication does not require any experimental parameters; it could potentially
      provide useful and precise prediction of permeability for new drugs or other
      penetrants.

PMID- 16306007
TI  - An ex vivo model of hematopoietic stem cell mobilization.
AB  - BACKGROUND: Mobilization of hematopoietic stem cells to the circulation
      facilitates their collection, thereby providing a non-marrow source of these
      cells for transplantation. Hematopoietic cytokine administration induces
      mobilization for most, but not all, donors. Because the underlying biology of
      mobilization is not well understood, improving the process on a rational basis is
      difficult. The design of an in vitro mobilization model was pursued to facilitate
      investigations of the process. METHODS: MS5 murine stromal cell line cells were
      grown to confluence on microporous transwell membranes. Murine femoral marrow
      plugs were placed on top of the prepared transwell membranes. The transwells were
      then seated in wells containing media and hematopoietic growth factors. Cells
      that were released from the marrow plugs over time and migrated through the
      stromal layer into the wells were assayed for stem cell/progenitor cell
      characteristics. RESULTS: Few or no GM-CSF (progenitors) were found in wells
      containing media alone or media plus mobilizing cytokines after 24 h. After 120
      h, the numbers of cells in the cytokine-containing wells increased, as did the
      numbers of CD34(+) cells. Cells in the wells at the time progenitor cells were
      most frequent were shown to include side population (SP) hematopoietic stem
      cells. After 120 h in the presence of cytokines, cells pooled from the wells were
      transplanted to lethally irradiated mice. Eighty per cent of the transplanted
      mice survived 30 days or more, demonstrating that radioprotective stem cells were
      present in the wells. DISCUSSION: An ex vivo model has been designed that may aid
      investigations of the various steps of stem cell mobilization.

PMID- 16306008
TI  - Ex vivo expansion of neutrophil precursor cells from mobilized peripheral blood
      cells: similar results in cancer patients and normal donors.
AB  - BACKGROUND: Infusion of ex vivo differentiated myeloid progenitors may reduce or
      abrogate severe neutropenia following mobilized peripheral blood transplantation.
      We compared the ex vivo expansion of myeloid progenitor cells starting from
      cancer patients (CP) and from normal donors (ND) and evaluated the influence of
      the CD34(+) cell mobilization on the capacities of cells to be expanded. METHODS:
      The ex vivo-expanded cells were evaluated for their phenotype, the presence of
      primary and secondary granules and their functional capacities (oxidative burst
      activity and phagocytosis). RESULTS: We did not observe significant differences
      between ND and CP for the total leukocyte and CD34(+) cell expansions nor for the
      myeloid progenitor production. In CP as well as in ND, the expanded cells were
      functionally competent. DISCUSSION: This suggests that the capacities of CD34(+)
      cells to proliferate and differentiate ex vivo are not impaired by prior
      chemotherapy and/or disease status. On the other hand, we did not observe any
      significant correlation between the number of mobilized CD34(+) cells before
      apheresis and the cell expansion. In conclusion, the ex vivo expansion of CP and
      ND cells is comparable and achievable even with a low CD34(+) cell number in
      mobilized peripheral blood.

PMID- 16306009
TI  - BM micrometastases and circulating tumor cells in breast cancer patients: where
      have we been, where are we now and where does the future lie?
AB  - Over the past 15 years early tumor cell dissemination has been detected in
      patients with breast cancer using sensitive immunocytochemical and molecular
      assays based on the use of MAb and PCR, respectively. Clinical studies involving
      more than 4,000 breast cancer patients have now demonstrated that the presence of
      disseminated tumor cells in BM identified with immuncytochemical assays at
      primary diagnosis is a strong and independent prognostic factor. The published
      studies for the detection of disseminated tumor cells in BM fulfill the highest
      level of evidence as prognostic markers in primary breast cancer. In addition,
      various assays for the detection of circulating tumor cells in the peripheral
      blood have been developed recently and some studies suggest a potential clinical
      relevance of this parameter as a prognostic and predictive factor. Comparative
      analyzes indicate that the prognostic information derived from BM and blood
      screening seems to be complementary and not redundant. Advanced methods for
      molecular characterization of single tumor cells and the surrounding environment
      have been developed lately, and this approach allows new insights into the
      metastatic cascade and characterization of targets for therapeutic approaches.
      Taken together, these findings provide the basis for the implementation of
      disseminated tumor cells in BM or blood as markers for stratification and
      assessment of therapies in prospective clinical trials. The valuable information
      derived from these trials should help to improve future treatment of breast
      cancer patients.

PMID- 16306010
TI  - BM-derived cells restore expression of peroxiredoxin V in the airways following
      acute naphthalene injury in mice.
AB  - BACKGROUND: Naphthalene-induced respiratory tract toxicity in mice is
      characterized by specific and rapid loss of the Clara cell population, which is
      restored only after several days. The sources of restoration of this cell
      population remain unclear. We investigated whether BM-derived cells participated
      in the process of epithelial restoration following naphthalene toxicity compared
      with bacterial infection. We further investigated the role of BM-derived cells in
      restoration of expression of peroxiredoxin V (PRXV), one of the major proteins of
      antioxidant defense, specifically expressed in the bronchial epithelium. METHODS:
      We transplanted GFP-tagged BM cells into 5 Gy-irradiated C57BL/6 recipients.
      Following 1 month of recovery, experimental animals were subjected to 250 mg/kg
      naphthalene i.p. An additional group of animals received intratracheal
      instillation of Escherichia coli to induce acute bacterial inflammation. Animals
      were killed at 1-12 days after naphthalene and analyzed immunohistochemically.
      RESULTS: Recipients' cells of bronchial epithelium demonstrated significantly
      reduced levels of PRXV expression following naphthalene. In animals with acute
      bacterial inflammation, PRXV levels were not reduced in epithelium and
      participation of BM-derived cells in epithelial restoration was minimal.
      Following naphthalene, GFP(+) cells were present in large numbers in lung
      parenchyma and epithelium of conducting airways starting at 1 day following
      injury. GFP(+) progeny of BM cells was the major source of PRXV in the
      epithelium. DISCUSSION: These data suggest that BM-derived cells may provide a
      source of antioxidant protection of airways by expression of PRXV in a model of
      acute epithelial respiratory tract toxicity.

PMID- 16306011
TI  - Long-lasting improvement of myocardial perfusion and chronic refractory angina
      after autologous intramyocardial PBSC transplantation.
AB  - We report the case of a 60-year-old man with patent coronary by-pass grafts on
      the left anterior descending and circumflex coronary arteries, who experienced
      recurrent Canadian class IV angina refractory to medical and interventional
      treatments for a dominant right coronary artery occlusion. He underwent
      autologous PBSC transplant into the inferior ventricular wall through a minimally
      invasive approach as a stand-alone therapy, in an attempt to induce therapeutic
      angiogenesis. Six months after the operation, angina significantly ameliorated;
      scintigraphy and coronary angiography showed a marked improvement in perfusion of
      the target injection area. These benefits had persisted at 25 months after stem
      cell transplant.

PMID- 16306012
TI  - An improved definition of mouse mammary epithelial side population cells.
AB  - BACKGROUND: Mammary epithelial side population cells have been suggested as
      candidate mammary stem cells. To date, for technical reasons, these cells have
      been poorly defined and cross-comparison of data between different laboratories
      has been difficult. Here, we set out to define mammary side population cells in a
      way that improves the ability to carry out such comparisons. METHODS: Mouse
      mammary epithelial cells were stained with Hoechst 33342. Light scatter, PI
      staining and clonogenicity of different regions of the Hoechst profile were
      examined. Time-course analyzes of Hoechst 33342 loading were carried out.
      RESULTS: Detailed examination of the light scatter and PI staining of Hoechst
      33342-stained mammary cells enabled single live side population and non-side
      population cells to be defined with greater accuracy. Comparison of ABC pump
      inhibitors identified potential discrepancies in results obtained using these
      inhibitors. Time-course analyzes enabled side populations cells to be identified
      as a dynamic cell population that could be defined accurately by using the
      relationship between Hoechst 33342-staining profiles of consecutive time points.
      DISCUSSION: Defining the side population of solid tissues as a 'stabilized side
      population percentage' will enable a more rigorous study of the side population
      phenomenon and improve evaluation of results from different laboratories.

PMID- 16306013
TI  - Outgrowth of a transformed cell population derived from normal human BM
      mesenchymal stem cell culture.
AB  - BACKGROUND: Human mesenchymal stem cells (hMSC) have been isolated and
      characterized extensively for a variety of clinical applications. Yet it is
      unclear how the phenomenon of hMSC plasticity can be safely and reasonably
      exploited for therapeutic use. METHODS: We have generated mesenchymal stem cells
      (MSC) from normal human BM and identified a novel cell population with a
      transformed phenotype. This cell population was characterized by morphologic,
      immunophenotypic, cytogenetic analyzes and telomerase expression. Its
      tumorigenicity in NOD/SCID mice was also studied. RESULTS: A subpopulation of
      cells in hMSC culture was noted to appear morphologically distinct from typical
      MSC. The cells were spherical, cuboidal to short spindle in shape, adherent and
      exhibited contact independent growth. Phenotypically the cells were CD133(+),
      CD34(-), CD45(-), CD90(low), CD105(-), VEGFR2(+). Cytogenetic analysis showed
      chromosome aneuploidy and translocations. These cells also showed a high level of
      telemerase activity compared with typical MSC. Upon transplantation into NOD/SCID
      mice, multiple macroscopic solid tumors formed in multiple organs or tissues.
      Histologically, these tumors were very poorly differentiated and showed
      aggressive growth with large areas of necrosis. DISCUSSION: The possible
      explanations for the origin of this cell population are: (1) the cells represent
      a transformed population of MSC that developed in culture; (2) abnormal cells
      existed in the donor BM at rare frequency and subsequently expanded in culture.
      In either case, the MSC culture may provide a suitable environment for
      transformed cells to expand or propagate in vitro. In summary, our data
      demonstrate the potential of transformed cells in hMSC culture and highlight the
      need for karyotyping as a release criteria for clinical use of MSC.

PMID- 16306014
TI  - Differentiation of transplanted mesenchymal stem cells in a large osteochondral
      defect in rabbit.
AB  - BACKGROUND: Although accumulating evidence shows that mesenchymal stem cells
      (MSC) are a promising cell source for articular cartilage repair, the fate of
      transplanted MSC has not been extensively studied. METHODS: To monitor their
      persistence and differentiation, we labeled uninduced MSC with a fluorescent dye,
      PKH26, and transplanted them, in a poly-glycolic-acid scaffold, to full-thickness
      defects made in the weight-bearing area of rabbit femoral trochleae with
      hyaluronate sheets. The fate of the labeled cells was monitored for up to 8
      weeks. RESULTS: Two weeks after transplantation, immature cartilage containing
      collagen type II had formed. By 8 weeks, this cartilage had thinned and
      immunolabeling for collagen type II gradually disappeared from the basal region,
      which became positive for collagen type I. Most chondrocytes within the
      regenerated cartilage were PKH26-positive and, therefore, derived from
      transplanted MSC, whereas osteoblasts within the regenerated bone were a mixture
      of donor- and host-derived cells. The thickness of the cartilage became thinner
      up to 8 weeks and then remained stable up to 42 weeks after surgery. DISCUSSION:
      These results showed that uninduced MSC were able to survive osteochondral
      defects and differentiated according to the environment, making a major
      contribution to initial cartilage formation and a partial contribution to bone
      regeneration.

PMID- 16306015
TI  - Roadmap to approval: use of an automated sterility test method as a lot release
      test for Carticel, autologous cultured chondrocytes.
AB  - BACKGROUND: In February 2004, FDA approved a supplement to our biologics license
      for Carticel, autologous cultured chondrocytes, to use the BacT/ALERT microbial
      detection system as an alternative to the compendial sterility test for lot
      release. This article provides a roadmap to our approval process. The approval
      represents more than 4 years of development and validation studies comparing the
      Steritest compact system to the BacT/ALERT microbial detection system. METHODS:
      For this study, freshly cultured chondrocytes were prepared from a characterized
      cell bank. Microbial isolates were prepared from either American Type Culture
      Collection (ATCC) strains or from in-house contaminants. For each test condition,
      a suspension of chondrocyte cells and test organisms was inoculated into both
      aerobic media (SA standard adult culture bottles, FA FAN, tryptic soy broth) and
      anaerobic media (SN standard adult culture bottles, FN FAN, fluid thioglycollate
      media) and tested for sterility using the Steritest compact system (Millipore,
      Bedford, MA, USA) and the BacT/ALERT microbial detection system (bioMerieux,
      Durham, NC, USA). Negative control bottles were inoculated with chondrocytes and
      no microorganisms. All bottles were incubated for 14 days and read daily.
      Bacterial growth was determined by either visual examination of Steritest
      canisters or detection of a positive by the BacT/ALERT system. A gram stain and
      streak plate were used to confirm positive bottles and negative bottles after 14
      days. RESULTS: The detection of a positive by either the Steritest compact system
      or the BacT/ALERT system was summarized for each organism in each validation
      study. Data generated from studies reducing the incubation temperature from 35
      degrees C to 32 degrees C improved detection times in the automated method
      compared with the compendial method. Other improvements included the use of FAN
      aerobic and anaerobic media to absorb the gentamicin contained in the culture
      media of prepared chondrocyte samples. Chondrocytes alone did not generate
      positive results in either the compendial method or the automated method.
      DISCUSSION: Data from validation studies support the use of the BacT/ALERT
      microbial detection system as an alternative sterility test for Carticel.

PMID- 16306016
TI  - Inhibition of return in children with Tourette's syndrome and comorbid forms: a
      preliminary study.
AB  - BACKGROUND: This study investigated the nature and functioning of the visual
      spatial inhibition of return (IOR) phenomenon in children with "pure" Tourette's
      syndrome (TS), and those with comorbid forms of TS. METHOD: Children with TS-only
      and "TS + comorbid" (TS + ADHD +/- OCD) and matched controls performed the
      inhibition of return (IOR) task, which involved responding to left and right
      visual targets appearing on a computer screen that were preceded by congruent or
      incongruent exogenous visual cues. RESULTS: The TS-only group performed similarly
      on the IOR task to the controls. When the TS-only group was subdivided into
      children with mild and severe TS symptoms, a post hoc comparison between the
      controls and severe TS symptom children revealed that these TS children had a
      reduced magnitude of IOR for targets appearing in the right visual field. The
      comparison between the TS + comorbid and controls revealed an atypical IOR
      pattern for the TS + comorbid group. They displayed a loss of normal facilitatory
      and inhibitory effects for right visual field targets. CONCLUSIONS: The findings
      suggest abnormalities in attentional "disengage" and "move" mechanisms in TS when
      directing attention to the right visual field, which may reflect left posterior
      parietal, superior colliculus, and midbrain pathology.

PMID- 16306017
TI  - Finger gnosia: a predictor of numerical abilities in children?
AB  - This paper aimed to test the specificity of predicting power of finger gnosia on
      later numerical abilities in school-age children and to contribute to the
      understanding of this effect. Forty-one children were tested in the beginning of
      Grade 1 on finger gnosia, left-right orientation (another sign of the Gerstmann
      "syndrome"), and global development. Fifteen months later, numerical and reading
      abilities were assessed. Analyses of the results indicated that, contrary to the
      general measures of cognitive development, performance in the finger gnosia test
      was a good predictor of numerical skills 1 year later but not of reading skills,
      which proves the specificity of that predictor. The same conclusion was also true
      for the left-right orientation. However, finger gnosia could equally predict
      performance in numerical tasks that do or do not rely heavily on finger
      representation or on magnitude representation. Results are discussed in terms of
      the localizationist and the functional hypotheses.

PMID- 16306018
TI  - Age-related trends in Stroop and conflicting motor response task findings.
AB  - Inhibition problems are reportedly at the heart of several childhood pathologies
      and learning disorders, but few instruments are available for their in-depth
      investigation. The main aim of the present study was to investigate the
      development of a capacity to inhibit automatic responses in young and middle
      childhood. For this purpose, 100 children between 6 and 11 years old were
      administered two tests that measure executive inhibition: an animal Stroop task
      (in a paper-and-pencil version of the computerized original proposed by Wright
      and colleagues in 2003) and a conflicting motor response task. Our results
      indicate that performance clearly improves in both tests during the course of a
      child's development and the data obtained with the paper-and-pencil animal Stroop
      task overlap with those obtained with the computerized version. When the task
      calls for a stronger inhibitory control (the incongruent situation in the Stroop
      task and in the opposite condition in the conflicting motor response test) the
      trend of the response times is less homogeneous, peaking in the youngest and
      oldest age brackets considered. The positivity and significance of the
      correlation coefficients between the two tests also suggest that the two measures
      are tapping cognitive abilities that are developing in a parallel fashion.

PMID- 16306019
TI  - Latent inhibition and asymmetrical visual-spatial attention in children with
      ADHD.
AB  - The research was designed to determine whether the purported hemispheric
      asymmetries that are associated with attention deficit/hyperactivity disorder
      (ADHD) affect performance on a selective attention visual search task, and
      whether any obtained asymmetry will be modulated by methylphenidate. Two groups
      of children (8-15 years) with ADHD, one with methylphenidate treatment (ADHD+)
      and one without (ADHD+), were compared to matched controls on a two-stage visual
      search task. The task assessed right-left visual field asymmetries and the
      effects of changing a previous distractor into a target. Such a procedure,
      related to latent inhibition (LI; poorer performance to a previously irrelevant
      stimulus than to a novel one), can provide evidence for dysfunctional processing
      of irrelevant stimuli. All three groups exhibited the LI effect. The ADHD group,
      however, exhibited less LI for left- than right-side targets, an effect absent in
      the control and ADHD+ groups, suggesting a lateralized attentional deficit for
      ADHD+ that was normalized by methylphenidate.

PMID- 16306020
TI  - Utility of a CPT in diagnosing ADHD among a representative sample of high-risk
      children: a cautionary study.
AB  - Continuous performance tests (CPTs) are widely used in the assessment and study
      of attention deficit hyperactivity disorder (ADHD). Although CPTs have reliably
      found differences between children with ADHD and normal controls, discriminating
      between children with ADHD and children with subclinical levels of behavioral or
      cognitive problems is a more clinically relevant and difficult endeavor.
      Additionally, most studies use convenience samples from clinical care settings
      that may not represent the ADHD population as a whole. The current study assessed
      the utility of a clinically used CPT, the Test of Variables of Attention (TOVA),
      in distinguishing between children with ADHD and children with subclinical levels
      of attention/behavior problems. Participants constituted a representative sample
      of elementary school students at high risk for ADHD, including 116 children with
      ADHD and 51 subclinical controls. Results found no significant differences
      between the ADHD and subclinical group on CPT variables, and CPT performance did
      not reliably predict group membership. Implications of the findings are
      discussed.

PMID- 16306021
TI  - Test review: Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV).

PMID- 16306023
TI  - The impact of periventricular brain injury on reading and spelling abilities in
      the late elementary and adolescent years.
AB  - The present study was designed: (1) to investigate the long-term consequences of
      both the presence and the severity of periventricular brain injury (PVBI) on
      intellectual, academic, and cognitive outcome in extremely-low-birthweight (ELBW:
      < 1,000 grams) children at a mean age of 11 years; and (2) to determine the
      nature of the underlying difficulties associated with academic problems in these
      children. The results indicated that ELBW children without PVBI performed as well
      as full-term children on intelligence, academic, and cognitive ability tests. In
      contrast, ELBW children with mild and severe PVBI achieved significantly lower
      scores than either ELBW children without PVBI or children who were born at term.
      A second analysis indicated that, after accounting for Full Scale IQ, working
      memory and phonological processing were significant predictors of reading and
      spelling performance in ELBW children. These findings suggest that the presence
      and severity of PVBI, and not ELBW status alone, is associated with performance
      on tests of intelligence, and academic and cognitive functioning, and that some
      of the same factors known to be associated with learning disabilities in full
      term children contribute to learning disabilities in ELBW children.

PMID- 16306024
TI  - Mental rotation of letters, pictures, and three-dimensional objects in German
      dyslexic children.
AB  - This study examines mental rotation ability in children with developmental
      dyslexia. Prior investigations have yielded equivocal results that might be due
      to differences in stimulus material and testing formats employed. Whereas some
      investigators found dyslexic readers to be impaired in mental rotation, others
      did not report any performance differences or even superior spatial performance
      for dyslexia. Here, we report a comparison of mental rotation for letters, three
      dimensional figures sensu Shepard and Metzler, and colored pictures of animals or
      humans in second-grade German dyslexic readers. Findings indicate that dyslexic
      readers are impaired in mental rotation for all three kinds of stimuli. Effects
      of general intelligence were controlled. Furthermore, dyslexic children were
      deficient in other spatial abilities like identifying letters or forms among
      distracters. These results are discussed with respect to the hypotheses of a
      developmental dysfunction of the parietal cortex or a subtle anomaly in
      cerebellar function in dyslexic readers.

PMID- 16306025
TI  - Neuropsychological impairment as a consequence of football (soccer) play and
      football heading: a preliminary analysis and report on school students (13-16
      years).
AB  - Footballers run the risk of incurring mild head injury from a variety of sources,
      including the intentional use of the head to play the ball, known as heading.
      This paper presents a preliminary exploratory analysis of data collected to
      examine whether cumulative incidence of mild head injury, or cumulative heading
      frequency, are related to neuropsychological functioning in male adolescent
      footballers. In a quasi-experimental cross-sectional design, neuropsychological
      test scores of school team footballers were compared with those of similarly aged
      rugby players and noncontact sport players. Cumulative mild head injury incidence
      was estimated using self-reports, and cumulative heading was estimated using a
      combination of observation and self-reports. No participants had sustained a head
      injury within 3 months of testing. There was no relationship between head injury
      and neuropsychological performance, and there were no decrements in either the
      footballers or the rugby players in comparison with the noncontact sport players.
      Within the footballers, cumulative heading did not predict any of the
      neuropsychological test scores. These findings indicate the absence of
      neuropsychological impairment arising due to cumulative mild head injury
      incidence, or cumulative heading. Although these null findings may be reassuring
      to players, parents, and football organizers, we stress that they are
      preliminary. Further data is being collected from the same populations to provide
      more reliable effect estimates.

PMID- 16306026
TI  - Development of prospective memory: tasks based on the prefrontal-lobe model.
AB  - This study investigated the development of prospective memory using tasks based
      on the prefrontal-lobe model. Three groups each of 30 children, adolescents, and
      young adults were compared on prospective-memory performance using ongoing tasks
      with two levels of cognitive demand (low and high), and two levels of importance
      (unstressed and stressed) of remembering prospective cues. The Self-Ordered
      Pointing Task (SOPT), Stroop Color Word Interference Test, and Tower of London
      were also used to assess relationships between prospective memory and prefrontal
      lobe functions. The children remembered fewer prospective cues than either the
      adolescents or adults, but the adolescents and adults remembered equally well.
      This trend increased significantly as the cognitive demand of the ongoing tasks
      increased. However, stressing or not stressing the importance of remembering made
      no difference to prospective-memory performance. Performance on the SOPT and
      Stroop Colour Word Interference predicted performance on the high- but not on the
      low-demand condition. These findings implicate the maturation of the brain's
      prefrontal region in the development of prospective memory.

PMID- 16306027
TI  - Acute pulmonary toxicity caused by exposure to colloidal silica: particle size
      dependent pathological changes in mice.
AB  - To compare the pulmonary toxicity between ultrafine colloidal silica particles
      (UFCSs) and fine colloidal silica particles (FCSs), mice were intratracheally
      instilled with 3 mg of 14 nm UFCSs and 230 nm FCSs and pathologically examined
      from 30 minutes to 24 hour postexposure. Histopathologically, lungs exposed to
      both sizes of particles showed bronchiolar degeneration and necrosis,
      neutrophilic inflammation in alveoli with alveolar type II cell swelling and
      particle-laden alveolar macrophage accumulation. UFCSs, however, induced
      extensive alveolar hemorrhage compared to FCSs from 30 minutes onwards. UFCSs
      also caused more severe bronchiolar epithelial cell necrosis and neutrophil
      influx in alveoli than FCSs at 12 and 24 hours postexposure. Laminin positive
      immunolabellings in basement membranes of bronchioles and alveoli of UFCSs
      treated animals was weaker than those of FCSs-treated animals in all observation
      times. Electron microscopy demonstrated UFCSs and FCSs on bronchiolar and
      alveolar wall surface as well as in the cytoplasm of alveolar epithelial cells,
      alveolar macrophages and neutrophils. Type I alveolar epithelial cell erosion
      with basement membrane damage in UFCSs treated animals was more severe than those
      in FCSs-treated animals. At 12 and 24 hours postexposure, bronchiolar epithelial
      cells in UFCSs-treated animals showed more intense vacuolation and necrosis
      compared to FCSs-treated animals. These findings suggest that UFCSs have greater
      ability to induce lung inflammation and tissue damages than FCSs.

PMID- 16306028
TI  - Investigation of initial changes in the mouse olfactory epithelium following a
      single intravenous injection of vincristine sulphate.
AB  - To investigate initial changes in the olfactory epithelium, vincristine sulphate
      (VCR) was administered intravenously once to male BALB/c mice on day 1 in
      comparison with unilateral bulbectomy (UBT). The light and electron microscopy of
      the olfactory epithelium, nerve and/or bulb with BrdU-morphometry was performed
      sequentially. Further, whole-body radioluminography was conducted at 1 and 24
      hours postdose. Apoptosis and an increased number of mitotic cells with a
      tendency toward decreasing BrdU-positive olfactory epithelial cell counts were
      observed in olfactory epithelial cells at 6 hours postdose of VCR and became more
      pronounced at 24 hours postdose. These changes disappeared on days 4 or 15, but
      minimal axonal degeneration was seen in the olfactory nerve from day 4 onward.
      Semiquantitative measurement of VCR levels in the ethmoturbinals elicited high
      drug retention even 24 hours after administration. In contrast, UBT showed no
      effect on mitosis and BrdU-positive cell counts at 6 hours postdose, but severe
      lesions in the olfactory epithelium and nerve were seen on days 2, 4, and/or 15.
      The above results suggest that the initial event of VCR-induced apoptosis in the
      mouse olfactory epithelium would be mitotic arrest with high drug retention,
      unlike that evoked by UBT.

PMID- 16306029
TI  - Extraskeletal osteosarcoma with cystic appearance in an aged Sprague-Dawley rat.
AB  - Extraskeletal osteosarcoma, arising spontaneously from the subcutis of the left
      abdomen and having a cystic appearance, was found in an untreated male Sprague
      Dawley rat during a carcinogenicity study. At 76 weeks of age, the tumor mass had
      grown to 50 x 110 x 140 mm, and the animal exhibited severe anemia related to the
      complication of ulceration with hemorrhage. The tumor displayed irregular
      ossification at the walls of a cyst-like space filled with much yellowish fluid
      and necrotic cellular debris. Histopathologically, the tumor consisted of sheets
      of large, plump osteoblast-like cells, which produced broad irregular trabeculae
      of osteoid and calcified osseous tissue. Since extraskeletal osteosarcoma with a
      cystic appearance, has not been reported in animals, except for the
      telangiectatic type, our case shows an extremely rare type.

PMID- 16306030
TI  - Comparison of two once-daily regimens with a regimen consisting of nelfinavir,
      didanosine, and stavudine in antiretroviral therapy-naive adults: 48-week results
      from the Antiretroviral Regimen Evaluation Study (ARES).
AB  - BACKGROUND: To improve the dosing frequency and pill burden of antiretroviral
      therapy, we compared two once-daily dosed regimens to a twice-daily dosed
      regimen. METHOD: HIV-1-infected, antiretroviral drug-naive adults were randomized
      to either twice-daily nelfinavir and stavudine and once-daily didanosine (regimen
      A) or simplified once-daily dosed antiretroviral regimens consisting of
      nevirapine, didanosine, and lamivudine (regimen B) or saquinavir, ritonavir,
      didanosine, and lamivudine (regimen C). RESULTS: At 48 weeks of therapy, the
      proportion of patients with a blood plasma HIV-1 RNA concentration (pVL) <50
      copies/mL by intention-to treat analysis was 42.3%, 50.0%, and 56.5% for regimens
      A (n = 26), B (n = 22), and C (n = 23), respectively. The time to a pVL <50
      copies/mL for the first time was significantly shorter in regimen C, and there
      was significantly more progression to CDC events in regimen B. These differences
      are possibly due to differences in baseline characteristics. Adverse events were
      lowest for regimen C; more signs associated with mitochondrial toxicity occurred
      in regimen A. Increase in CD4 count was comparable between arms. CONCLUSION: No
      statistically significant difference in efficacy was found between the two
      investigated once-daily dosed treatment regimens (B and C) and the reference (A).
      Regimen C possibly had a better virological response and less toxicity than
      regimens A and B.

PMID- 16306031
TI  - Pharmacokinetics of clarithromycin extended-release (ER) tablets in patients with
      AIDS.
AB  - BACKGROUND: Clarithromycin is a key agent in effective antimycobacterial therapy
      and prophylaxis for AIDS-related disseminated Mycobacterium avium complex (dMAC)
      infection. Immediate-release (IR) clarithromycin tablets are dosed at 500 mg bid
      for these indications. A new extended-release (ER) tablet of clarithromycin has
      been developed and approved at a dosing interval of once every 24 hours for
      treatment of respiratory tract bacterial infections. However, the
      pharmacokinetics of clarithromycin ER in AIDS patients with or at risk for dMAC
      has not been previously investigated. METHOD: We conducted a randomized,
      crossover trial in which 14 AIDS patients received clarithromycin ER, 1000 mg
      once daily, and clarithromycin IR, 500 mg bid, each for 1 week, with
      pharmacokinetic sampling at the end of each week. RESULTS: The mean of the
      individual AUC ratios for clarithromycin ER vs. IR was 1.09 (90% CI, 0.94-1.24).
      Adverse events were no more severe or frequent with clarithromycin ER than IR.
      CONCLUSION: Clarithromycin ER is a once-daily regimen that is as well tolerated
      as standard bid IR clarithromycin dosing and has average bioequivalence to the IR
      formulation in patients with AIDS.

PMID- 16306032
TI  - Pharmacokinetics of nevirapine: once-daily versus twice-daily dosing in the 2NN
      study.
AB  - OBJECTIVE: As part of the large international, randomized 2NN trial, the
      pharmacokinetics of nevirapine in once-daily 400 mg and twice-daily 200 mg dosing
      regimens were investigated. METHOD: Treatment-naive HIV-1-infected patients were
      randomized to receive nevirapine 400 mg once daily or 200 mg twice daily, in
      combination with lamivudine and stavudine. Blood samples were collected at
      several time-points (day 3, weeks 1, 2, 4, 24, and 48). Differences in
      pharmacokinetics between once- versus twice-daily dosing were investigated with
      nonlinear mixed effects modelling (NONMEM). RESULTS: In total, 2,899 nevirapine
      plasma concentrations were available from 578 patients. Dosage and dosing
      frequency did not influence clearance or volume of distribution of nevirapine,
      indicating linear pharmacokinetic behavior of nevirapine whether given as a
      single daily dose or as divided doses over 24 hours. During steady state, the
      Cmin was lower (3.26 mg/L vs. 4.44 mg/L; p < .001) and the Cmax was higher (7.88
      mg/L vs. 6.55 mg/L; p < .001) in the once-daily arm. However, compared to total
      variability in nevirapine levels for both treatments, these differences were
      minor. During steady state, total exposure, measured as AUC24h, was comparable
      for both regimens (133 mg/L*h vs. 133 mg/L*h; p = .084). CONCLUSION: The daily
      exposure to nevirapine (AUC24h) was similar for the 400 mg once-daily and the 200
      mg twice-daily dosing regimens. The Cmin of nevirapine is lower and the Cmax of
      nevirapine is higher for the once-daily regimen as compared to the twice-daily
      regimen. As a result, 200 mg nevirapine dosed twice daily may be preferred over
      400 mg nevirapine dosed once daily.

PMID- 16306033
TI  - Human immunodeficiency virus (HIV) entry inhibitors (CCR5 specific blockers) in
      development: are they the next novel therapies?
AB  - Since the introduction of the nucleoside reverse transcriptase inhibitor
      zidovudine in 1987, the number of the available antiretroviral medications has
      grown to about 20. Despite the efficacy of these medications, treatment-limiting
      adverse events are frequent. During the last several years, a new class of
      antiretroviral drugs often referred to as entry inhibitors, specifically the CCR5
      blockers, have moved from the basic science laboratories and are now in the
      clinical phases of drug development. There are three agents in phase 2/3
      development that inhibit viral entry by binding to CCR5, disrupting the
      interaction between the co-receptor and viral glycoprotein (gp) 120. They are
      aplaviroc (GW-873140), maraviroc (UK-427,857), and vicriviroc (SCH 417690). The
      development of these new antiviral agents that target different aspects of the
      viral life cycle is likely to make it possible to suppress viral strains that are
      resistant to the currently available antiretroviral drugs. There is a growing
      need for a new class of antiretrovirals with reduced toxicity and improved
      tolerability. However, currently available information suggests further
      pharmacokinetics, resistance, safety, and efficacy data are needed to understand
      how these agents may be effectively used in the clinical setting.

PMID- 16306034
TI  - Hepatic and renal safety profile of tenofovir in HIV-infected patients with
      hepatitis C, including patients on interferon plus ribavirin.
AB  - The liver safety of tenofovir (TDF) was investigated in 142 HIV+ patients exposed
      to the drug for longer than 12 months. No evidence of liver enzyme elevations
      were seen, even in 66 patients with chronic hepatitis C virus (HCV) co-infection.
      Given that TDF is an adenosine analogue, like didanosine, exposure to ribavirin
      might increase intracellular phosphorylated TDF metabolites, which could result
      in a higher risk of nephrotoxicity. Signs of tubular dysfunction in blood or
      urine were not recognized in 17 HCV-HIV co-infected patients exposed to TDF
      during interferon plus ribavirin therapy.

PMID- 16306035
TI  - Importance of small (< or = 20-mm) enhancing lesions seen only during the hepatic
      arterial phase at MR imaging of the cirrhotic liver: evaluation and comparison
      with whole explanted liver.
AB  - PURPOSE: To retrospectively assess the importance and imaging appearance of small
      (< or = 20 mm in diameter) hepatic arterial phase-enhancing (HAPE) lesions that
      are occult during portal and/or equilibrium phases and at unenhanced T1- and T2
      weighted magnetic resonance (MR) imaging and to determine the gross pathologic
      diagnosis with whole-liver explant comparison. MATERIALS AND METHODS: This
      retrospective study was approved by the institutional review board and compliant
      with HIPPA. Forty-six patients with cirrhosis who underwent MR imaging and
      transplantation within 90 days were evaluated with breath-hold T2-weighted and
      volumetric three-dimensional gadolinium-enhanced gradient-echo MR imaging in the
      hepatic arterial, portal venous, and equilibrium phases at 1.5 T. Three readers,
      who were blinded to the pathologic results, retrospectively reviewed the MR
      images in consensus for small HAPE nodules that were occult at T2-weighted and
      portal and/or equilibrium phase MR imaging. Only patients with nodules that
      enhanced during the arterial phase were included in the final study group, which
      included 16 patients (12 men and four women) aged 18-66 years (median age, 51.5
      years). Explanted livers were serially sliced into 5-8-mm-thick sections to
      evaluate dysplastic nodules and hepatocellular carcinomas (HCCs). The Fisher
      exact test was performed to determine whether there was a relationship between
      HCC and the presence of a neoplastic HAPE-only lesion. The Mann-Whitney test was
      used to determine if patients with at least one neoplastic HAPE-only lesion had a
      larger number of non-HAPE-only lesions. RESULTS: The 16 patients had 45 HAPE-only
      lesions; three (7%) of which were neoplastic, including one overt HCC, one HCC
      arising in a dysplastic nodule, and one dysplastic nodule. None of the remaining
      42 HAPE-only lesions (93%) had correlative pathologic findings. All three
      neoplastic lesions seen only during the arterial phase were found in eight
      patients with concomitant HCC, who also had an additional 13 pathologically
      proved nonneoplastic HAPE-only lesions. In eight patients without HCC, none of
      the HAPE-only lesions were neoplastic. A concomitant non-HAPE-only neoplastic
      lesion was not a significant (P = .2) predictor for the presence of at least one
      neoplastic HAPE-only lesion. There was a preliminary but insignificant (P = .13)
      indication that the number of non-HAPE-only lesions tends to be higher in
      patients with neoplastic HAPE-only lesions. CONCLUSION: The majority (93%) of
      HAPE-only lesions that are occult at T2-weighted and portal and/or equilibrium
      phase MR imaging are nonneoplastic, even in patients with pathologically proved
      HCC.

PMID- 16306036
TI  - Locally recurrent central-type early stage lung cancer < 1.0 cm in diameter after
      complete remission by photodynamic therapy.
AB  - BACKGROUND: It is well known that central-type early stage lung cancer < 1.0 cm
      in diameter shows almost 100% complete response (CR) to photodynamic therapy
      (PDT). However, we have encountered cases of local recurrence after CR of tumors
      with a surface diameter < 1.0 cm. PATIENTS AND METHODS: Ninety-three patients
      with 114 lesions were followed up, and cases of recurrence after CR has been
      obtained with initial tumors that had a diameter < 1.0 cm were examined. We
      compared the cytologic findings of local recurrence after CR to the cytologic
      findings before PDT. The relationship between the cell features and the depth of
      bronchial tumor invasion before PDT and on recurrence was evaluated. RESULTS: The
      CR and 5-year survival rates of patients with lesions < 1.0 cm were 92.8% (77 of
      83 patients) and 57.9%, respectively; meanwhile, in the group of patients with
      lesions > or = 1.0 cm, CR and 5-year survival rates were 58.1% (18 of 31
      patients) and 59.3%. There was a significant difference in efficacy between the
      two groups (p < 0.001). Recurrences after CR were recognized in 9 of 77 lesions
      (11.7%) < 1.0 cm. When the recurrent tumor cells showed type I-II (low-to
      moderate atypia) at the same site initially treated, CR could be obtained by a
      second PDT. Type III cells (high-grade atypia) showed the characteristics of
      tumor cells from deeper layers of the bronchial wall. Local recurrence at the
      same site may be caused by residual tumor cells from deep layers because of
      inadequate laser irradiation and penetration. CONCLUSIONS: To reduce the
      recurrence rate, it is essential to accurately grasp the tumor extent and the
      depth of the bronchogenic carcinoma before performing PDT. Analysis of cell
      features of recurrent lesions after CR appears to be a useful source of
      information as to the depth of cancer invasion in the bronchial wall.

PMID- 16306037
TI  - Combining bronchoscopy and positron emission tomography for the diagnosis of the
      small pulmonary nodule < or = 3 cm.
AB  - AIM: To assess the role of bronchoscopy and positron emission tomography (PET)
      scanning in an integrated approach for the diagnosis of noncalcified, small,
      chest radiologic lesions (< or = 3 cm). METHODS: Seventy-four consecutive
      patients (29 men; mean age, 64 years) with a pulmonary nodule < or = 3 cm
      undergoing both combined PET and bronchoscopy were included. When bronchoscopy
      and PET findings were negative, a multidisciplinary decision was taken to perform
      further invasive diagnostics or follow-up. RESULTS: Malignancy was diagnosed in
      51 patients (69%), and a positive benign diagnosis was made in 9 patients (12%).
      Six patients (8%) had endobronchial lesions. Bronchoscopy was diagnostic in 53%
      patients (cancer, n = 35; benign, n = 4). PET findings were positive in 19 of 35
      patients with a nondiagnostic bronchoscopy. In these 19 patients, malignant
      diagnosis was made in 14 patients (CT-fine needle aspiration [FNA], n = 3;
      thoracoscopic biopsy, n = 3; resection, n = 7; FNA of PET-positive supraclaviclar
      lymph node, n = 1), and a benign diagnosis was made in 5 patients (CT-FNA, n = 1;
      thoracoscopic biopsy, n = 1; resection, n = 1; follow-up, n = 2). In 16 patients
      with nondiagnostic bronchoscopy and negative PET findings, 5 patients had a
      tissue diagnosis (cancer, n = 2 [< 1 cm]; benign, n = 3) and 11 patients were
      followed up. Sixty-seven patients had a lesion 11 mm to 3 cm; among these, all 12
      patients who were bronchoscopy negative and PET negative had benign lesions. In
      24 patients without mediastinal adenopathy (solitary pulmonary nodule),
      bronchoscopy was diagnostic in 12 patients (cancer, n = 11; bronchiolitis
      obliterans organizing pneumonia, n = 1). In the remaining 12 patients, PET
      findings were positive in 6 patients (cancer, n = 3; resection, n = 2; CT-FNA, n
      = 1) and negative in 6 patients (benign, n = 2, both on resection; follow-up, n =
      4). CONCLUSION: Combining bronchoscopy and PET scanning has an useful role in the
      diagnosis of noncalcified chest radiologic lesions < or = 3 cm in size.
      Bronchoscopy has a diagnostic yield of > 50% and also allows the diagnosis of
      endobronchial lesions. If bronchoscopy is nondiagnostic, a PET scan should be
      performed.

PMID- 16306038
TI  - Structural and biological identification of residues on the surface of NS3
      helicase required for optimal replication of the hepatitis C virus.
AB  - The hepatitis C virus (HCV) nonstructural protein 3 (NS3) is a multifunctional
      enzyme with serine protease and DEXH/D-box helicase domains. A crystal structure
      of the NS3 helicase domain (NS3h) was generated in the presence of a single
      stranded oligonucleotide long enough to accommodate binding of two molecules of
      enzyme. Several amino acid residues at the interface of the two NS3h molecules
      were identified that appear to mediate a protein-protein interaction between
      domains 2 and 3 of adjacent molecules. Mutations were introduced into domain 3 to
      disrupt the putative interface and subsequently examined using an HCV subgenomic
      replicon, resulting in significant reduction in replication capacity. The
      mutations in domain 3 were then examined using recombinant NS3h in biochemical
      assays. The mutant enzyme showed RNA binding and RNA-stimulated ATPase activity
      that mirrored wild type NS3h. In DNA unwinding assays under single turnover
      conditions, the mutant NS3h exhibited a similar unwinding rate and only
      approximately 2-fold lower processivity than wild type NS3h. Overall biochemical
      activities of the mutant NS3h were similar to the wild type enzyme, which was not
      reflective of the large reduction in HCV replicative capacity observed in the
      biological experiment. Hence, the biological results suggest that the known
      biochemical properties associated with the helicase activity of NS3h do not
      reveal all of the likely biological roles of NS3 during HCV replication. Domain 3
      of NS3 is implicated in protein-protein interactions that are necessary for HCV
      replication.

PMID- 16306039
TI  - Efficient and high fidelity incorporation of dCTP opposite 7,8-dihydro-8
      oxodeoxyguanosine by Sulfolobus solfataricus DNA polymerase Dpo4.
AB  - DNA polymerases insert dATP opposite the oxidative damage product 7,8-dihydro-8
      oxodeoxyguanosine (8-oxoG) instead of dCTP, to the extent of >90% with some
      polymerases. Steady-state kinetics with the Y-family Sulfolobus solfataricus DNA
      polymerase IV (Dpo4) showed 90-fold higher incorporation efficiency of dCTP >
      dATP opposite 8-oxoG and 4-fold higher efficiency of extension beyond an 8-oxoG:C
      pair than an 8-oxoG:A pair. The catalytic efficiency for these events (with dCTP
      or C) was similar for G and 8-oxoG templates. Mass spectral analysis of extended
      DNA primers showed >/=95% incorporation of dCTP > dATP opposite 8-oxoG. Pre
      steady-state kinetics showed faster rates of dCTP incorporation opposite 8-oxoG
      than G. The measured K(d)(,dCTP) was 15-fold lower for an oligonucleotide
      containing 8-oxoG than with G. Extension beyond an 8-oxoG:C pair was similar to
      G:C and faster than for an 8-oxoG:A pair, in contrast to other polymerases. The
      E(a) for dCTP insertion opposite 8-oxoG was lower than for opposite G. Crystal
      structures of Dpo4 complexes with oligonucleotides were solved with C, A, and G
      nucleoside triphosphates placed opposite 8-oxoG. With ddCTP, dCTP, and dATP the
      phosphodiester bonds were formed even in the presence of Ca(2+). The 8-oxoG:C
      pair showed classic Watson-Crick geometry; the 8-oxoG:A pair was in the syn:anti
      configuration, with the A hybridized in a Hoogsteen pair with 8-oxoG. With dGTP
      placed opposite 8-oxoG, pairing was not to the 8-oxoG but to the 5' C (and in
      classic Watson-Crick geometry), consistent with the low frequency of this
      frameshift event observed in the catalytic assays.

PMID- 16306041
TI  - Examining Ty3 polypurine tract structure and function by nucleoside analog
      interference.
AB  - We have combined nucleoside analog interference with chemical footprinting,
      thermal denaturation, NMR spectroscopy, and biochemical studies to understand
      recognition of the polypurine tract (PPT) primer of the Saccharomyces cerevisiae
      long terminal repeat-containing retrotransposon Ty3 by its cognate reverse
      transcriptase. Locked nucleic acid analogs, which constrain sugar ring geometry,
      were introduced pairwise throughout the PPT (-)-DNA template, whereas abasic
      tetrahydrofuran linkages, which lack the nucleobase but preserve the sugar
      phosphate backbone, were introduced throughout the (-)-strand DNA template and
      (+)-strand RNA primer. Collectively, our data suggest that both the 5'- and 3'
      portions of the PPT-containing RNA/DNA hybrid are sensitive to nucleoside analog
      substitution, whereas the intervening region can be modified without altering
      cleavage specificity. These two regions most likely correspond to portions of the
      PPT that make close contact with the Ty3 reverse transcriptase thumb subdomain
      and RNase H catalytic center, respectively. Achieving a similar phenotype with
      nucleoside analogs that have different effects on duplex geometry reveals
      structural features that are important mediators of Ty3 PPT recognition. Finally,
      the results from introducing tetrahydrofuran lesions around the scissile
      PPT/unique 3'-sequence junction indicate that template nucleobase -1 is
      dispensable for catalysis, whereas a primer nucleobase on either side of the
      junction is necessary.

PMID- 16306040
TI  - Sequence, distance, and accessibility are determinants of 5'-end-directed
      cleavages by retroviral RNases H.
AB  - The RNase H activity of reverse transcriptase is essential for retroviral
      replication. RNA 5'-end-directed cleavages represent a form of RNase H activity
      that is carried out on RNA/DNA hybrids that contain a recessed RNA 5'-end.
      Previously, the distance from the RNA 5'-end has been considered the primary
      determinant for the location of these cleavages. Employing model hybrid
      substrates and the HIV-1 and Moloney murine leukemia virus reverse
      transcriptases, we demonstrate that cleavage sites correlate with specific
      sequences and that the distance from the RNA 5'-end determines the extent of
      cleavage. An alignment of sequences flanking multiple RNA 5'-end-directed
      cleavage sites reveals that both enzymes strongly prefer A or U at the +1
      position and C or G at the -2 position, and additionally for HIV-1, A is
      disfavored at the -4 position. For both enzymes, 5'-end-directed cleavages
      occurred when sites were positioned between the 13th and 20th nucleotides from
      the RNA 5'-end, a distance termed the cleavage window. In examining the
      importance of accessibility to the RNA 5'-end, it was found that the extent of 5'
      end-directed cleavages observed in substrates containing a free recessed RNA 5'
      end was most comparable to substrates with a gap of two or three bases between
      the upstream and downstream RNAs. Together these finding demonstrate that the
      selection of 5'-end-directed cleavage sites by retroviral RNases H results from a
      combination of nucleotide sequence, permissible distance, and accessibility to
      the RNA 5'-end.

PMID- 16306042
TI  - A comparative study of uracil-DNA glycosylases from human and herpes simplex
      virus type 1.
AB  - Uracil-DNA glycosylase (UNG) is the key enzyme responsible for initiation of base
      excision repair. We have used both kinetic and binding assays for comparative
      analysis of UNG enzymes from humans and herpes simplex virus type 1 (HSV-1).
      Steady-state fluorescence assays showed that hUNG has a much higher specificity
      constant (k(cat)/K(m)) compared with the viral enzyme due to a lower K(m). The
      binding of UNG to DNA was also studied using a catalytically inactive mutant of
      UNG and non-cleavable substrate analogs (2'-deoxypseudouridine and 2'-alpha
      fluoro-2'-deoxyuridine). Equilibrium DNA binding revealed that both human and HSV
      1 UNG enzymes bind to abasic DNA and both substrate analogs more weakly than to
      uracil-containing DNA. Structure determination of HSV-1 D88N/H210N UNG in complex
      with uracil revealed detailed information on substrate binding. Together, these
      results suggest that a significant proportion of the binding energy is provided
      by specific interactions with the target uracil. The kinetic parameters for human
      UNG indicate that it is likely to have activity against both U.A and U.G
      mismatches in vivo. Weak binding to abasic DNA also suggests that UNG activity is
      unlikely to be coupled to the subsequent common steps of base excision repair.

PMID- 16306043
TI  - Negative regulation of the retinoic acid-inducible gene I-induced antiviral state
      by the ubiquitin-editing protein A20.
AB  - Activation of the interferon regulatory factors (IRFs) 3 and 7 transcription
      factors is essential for the induction of type I interferon (IFN) and development
      of the innate antiviral response. Retinoic acid-inducible gene I has been shown
      to contribute to virus-induced IFN production independent of the Toll-like
      receptor pathways in response to a variety of RNA viruses and double-stranded
      RNA. In the present study, we demonstrate that the NF-kappaB-inducible, anti
      apoptotic protein A20 efficiently blocks RIG-I-mediated activation of NF-kappaB-,
      IRF-3-, and IRF-7-dependent promoters but only weakly interferes with TRIF-TLR-3
      mediated IFN activation. Expression of A20 completely blocked CARD domain
      containing DeltaRIG-I-induced IRF-3 Ser-396 phosphorylation, homodimerization,
      and DNA binding. The level of A20 inhibition was upstream of the TBK1/IKKepsilon
      kinases that phosphorylate IRF3 and IRF7 and paradoxically, A20 selectively
      degraded the TRIF protein but not RIG-I. A20 possesses two ubiquitin-editing
      domains, an N-terminal deubiquitination domain and a C-terminal ubiquitin ligase
      domain consisting of seven zinc finger domains. Deletion of the N-terminal de
      ubiquitination domain had no significant effect on the inhibitory effect of A20,
      whereas deletion or mutation of zinc finger motif 7 ablated the inhibitory
      function of A20 on IRF- or NF-kappaB-mediated gene expression. Furthermore, cells
      stably expressing the active form of RIG-I induced an antiviral state that
      interfered with replication of vesicular stomatitis virus, an effect that was
      reversed by stable co-expression of A20. These results suggest that the virus
      inducible, NF-kappaB-dependent activation of A20 functions as a negative
      regulator of RIG-I-mediated induction of the antiviral state.

PMID- 16306044
TI  - Opposite roles of FAP-1 and dynamin in the regulation of Fas (CD95) translocation
      to the cell surface and susceptibility to Fas ligand-mediated apoptosis.
AB  - Human melanoma is the most aggressive form of skin cancer and is extremely
      resistant to radiation and chemotherapy. One of the critical parameters of this
      resistance is down-regulation of Fas (CD95) cell-surface expression. Using TIG3
      normal human fibroblasts and human melanoma cell lines, we investigated
      transcriptional regulation of FAP-1, a regulator of Fas translocation in the
      cell. Protein-tyrosine phosphatase FAP-1 (PTPN13, PTP-BAS) interacts with human
      Fas protein and prevents its export from the cytoplasm to the cell surface. In
      contrast, dynamin-2 facilitates Fas protein translocation from the Golgi
      apparatus via the trans-Golgi network to the cell surface. Suppression of dynamin
      functions by dominant negative dynamin K44A blocks Fas export, whereas the down
      regulation of FAP-1 expression by specific RNA interference restores Fas export
      (a phenomenon that could still be down-regulated in the presence of dominant
      negative dynamin). Based on the FAP-1- and dynamin-dependent regulation of Fas
      translocation, we have created human melanoma lines with different levels of
      surface expression of Fas. Treatment of these melanoma lines with soluble Fas
      ligand resulted in programmed cell death that was proportional to the pre
      existing levels of surface Fas. Taking into consideration the well known
      observations that FAP-1 expression is often up-regulated in metastatic tumors, we
      have established a causal connection between high basal NF-kappaB transcription
      factor activity (which is a hallmark of many types of metastatic tumors) and NF
      kappaB-dependent transcriptional regulation of FAP-1 gene expression that finally
      restricts Fas protein trafficking, thereby, facilitating the survival of cancer
      cells.

PMID- 16306045
TI  - Pheromone-regulated sumoylation of transcription factors that mediate the
      invasive to mating developmental switch in yeast.
AB  - A fundamental question in biology is how different signaling pathways use common
      signaling proteins to attain different developmental outcomes. The yeast
      transcription factor Ste12 is required in at least two distinct signaling
      processes, each regulated by many of the same protein kinases. Whereas Ste12
      Ste12 homodimers promote transcription of genes required for mating, Ste12-Tec1
      heterodimers activate genes required for invasive growth. We report that Ste12
      and Tec1 undergo covalent modification by the ubiquitin-related modifier SUMO.
      Stimulation by mating pheromone promotes sumoylation of Ste12 and diminishes the
      sumoylation of Tec1. In the absence of sumoylation Tec1 is more rapidly degraded.
      We propose that pheromone-regulated sumoylation of Ste12 and Tec1 promotes a
      developmental switch from the invasive to the mating differentiation program.

PMID- 16306046
TI  - Mechanical inhibition of RANKL expression is regulated by H-Ras-GTPase.
AB  - Mechanical input is known to regulate bone remodeling, yet the molecular events
      involved in mechanical signal transduction are poorly understood. We here
      investigate proximal events leading to the ERK1/2 activation that is required for
      mechanical repression of RANKL (receptor activator of NF-kappaB ligand)
      expression, the factor that controls local recruitment of osteoclasts. Using
      primary murine bone stromal cells we show that dynamic mechanical strain via
      substrate deformation activates Ras-GTPase, in particular the H-Ras isoform.
      Pharmacological inhibition of H-Ras function prevents strain activation of H-Ras
      as well as the downstream mechanical repression of RANKL. Furthermore, small
      interfering RNA silencing of H-Ras, but not K-Ras, abrogates mechanical strain
      repression of RANKL. H-Ras-specific inhibition of mechanorepression of RANKL was
      also demonstrated in a murine pre-osteoblast cell line (CIMC-4). The requirement
      of cholesterol for H-Ras activation was probed; cholesterol depletion of rafts
      using methyl-betacyclodextrin prevented mechanical H-Ras activation. That the
      mechanical repression of RANKL requires activation of H-Ras, a specific isoform
      of Ras-GTP that is known to reside in the lipid raft microdomain, suggests that
      spatial arrangements are critical for generation of specific downstream events in
      response to mechanical signals. By partitioning signals this way, cells may be
      able to generate different downstream responses through seemingly similar
      signaling cascades.

PMID- 16306047
TI  - Presenilin-1 interacts with plakoglobin and enhances plakoglobin-Tcf-4
      association. Implications for the regulation of beta-catenin/Tcf-4-dependent
      transcription.
AB  - Alzheimer disease-linked Presenilin-1 (PS1) is a negative modulator of beta
      catenin/Tcf-4 activity. However, the mechanism underlying this effect is not well
      understood. We show here that the effects of PS1 on the activity of this complex
      in epithelial cells are independent of its gamma-secretase activity and its
      interaction with beta-catenin. As presented in this report PS1 also binds
      plakoglobin with similar affinity as beta-catenin, although this interaction does
      not involve equivalent residues in the two catenins. Moreover, PS1 association
      with plakoglobin enhances the interaction of this molecule with Tcf-4 and
      prevents its binding to DNA. These effects were observed with the unprocessed
      form of PS1, which has higher affinity for plakoglobin and beta-catenin than
      processed PS1. These results provide a new explanation for the effects of PS1 on
      gene transcription mediated by beta-catenin in epithelial cells.

PMID- 16306048
TI  - Maintenance of olfactory neurogenesis requires HSF1, a major heat shock
      transcription factor in mice.
AB  - Heat shock transcription factors (HSFs) play roles not only in heat shock
      response but also in development of the reproductive organs, brain, and lens.
      Here, we analyzed sensory organs and found abnormalities of the olfactory
      epithelium in adult HSF1-null mice, which is developmentally related to the lens.
      The olfactory epithelium was normal until postnatal 3 weeks but was not
      maintained later than 4 weeks in HSF1-null mice. The olfactory epithelium was
      atrophied with increased cell death of olfactory sensory neurons. Analysis of the
      epithelium revealed that induction of HSP expression and reduction of LIF
      expression are lacking in adult HSF1-null mice. We found that DNA binding
      activity of HSF1 is induced in the olfactory epithelium later than 4 weeks and
      that HSF1 binds directly to Lif gene and inhibits its expression. HSF4 has
      opposing effects on LIF expression and olfactory neurogenesis. These data
      indicate that HSF1 is required for the precise expression of Hsp and cytokine
      genes that is obligatory for maintenance of olfactory neurogenesis in adult mice
      and suggest that stress-related processes are involved in its maintenance.

PMID- 16306049
TI  - A salvage pathway for phytol metabolism in Arabidopsis.
AB  - Chlorophyll is the most abundant photosynthetic pigment in higher plants. During
      senescence, chlorophyll is hydrolyzed, resulting in the release of free phytol
      and chlorophyllide. Although the degradation of chlorophyllide has been studied
      in depth, the metabolic fate of phytol in plants is less clear. Here, we provide
      evidence that phytol can be incorporated into chlorophyll, tocopherol, and lipid
      esters by Arabidopsis seedlings. Phytol is phosphorylated to phytyl-phosphate and
      phytyl-diphosphate by two successive kinase activities associated with
      chloroplast envelope membranes of Arabidopsis. Although phytol kinase is CTP
      dependent, the second kinase reaction, phytyl-phosphate kinase, shows broader
      specificity for CTP, GTP, UTP, and ATP. Therefore, in addition to de novo
      synthesis from geranylgeranyl-diphosphate, phosphorylation of free phytol
      represents an alternative route for phytyl-diphosphate production as the
      precursor for chloroplast prenyl lipid synthesis. Lipid esters are produced after
      feeding phytol to Arabidopsis seedlings, and they also accumulate in large
      amounts in leaves during senescence. The predominant phytyl ester that
      accumulates during senescence is hexadecatrienoic acid phytyl ester. Fatty acid
      phytyl ester synthesis by protein extracts of Arabidopsis is stimulated in the
      presence of phytol- and acyl-CoA esters. Thus, Arabidopsis contains a distinct
      enzymatic machinery for redirecting free phytol released from chlorophyll
      degradation into chloroplast lipid metabolism.

PMID- 16306050
TI  - Platelet-activating factor mediates MMP-2 expression and activation via
      phosphorylation of cAMP-response element-binding protein and contributes to
      melanoma metastasis.
AB  - Overexpression of cAMP-response element (CRE)-binding protein (CREB) and
      activating transcription factor (ATF) 1 contributes to melanoma progression and
      metastasis at least in part by promoting tumor cell survival and stimulating
      matrix metalloproteinase (MMP) 2 expression. However, little is known about the
      regulation of CREB and ATF-1 activities and their phosphorylation within the
      tumor microenvironment. We analyzed the effect of platelet-activating factor
      (PAF), a potent phospholipid mediator of inflammation, for its ability to
      activate CREB and ATF-1 in eight cultured human melanoma cell lines, and we found
      that PAF receptor (PAFR) was expressed in all eight lines. In metastatic melanoma
      cell lines, PAF induced CREB and ATF-1 phosphorylation via a PAFR-mediated signal
      transduction mechanism that required pertussis toxin-insensitive Galphaq protein
      and adenylate cyclase activity and was antagonized by a cAMP-dependent protein
      kinase A and p38 MAPK inhibitors. Addition of PAF to metastatic A375SM cells
      stimulated CRE-dependent transcription, as observed in a luciferase reporter
      assay, without increasing the CRE DNA binding capacity of CREB. Furthermore, PAF
      stimulated the gelatinase activity of MMP-2 by activating transcription and MMP-2
      expression. MMP-2 activation correlated with the PAF-induced increase in the
      expression of an MMP-2 activator, membrane type 1 MMP. PAF-induced expression of
      pro-MMP-2 was causally related to PAF-induced CREB and ATF-1 phosphorylation; it
      was prevented by PAFR antagonist and inhibitors of p38 MAPK and protein kinase A
      and was abrogated upon quenching of CREB and ATF-1 activities by forced
      overexpression of a dominant-negative form of CREB. PAF-induced MMP-2 activation
      was also down-regulated by p38 MAPK and protein kinase A inhibitors. Finally,
      PAFR antagonist PCA4248 inhibited the development of A375SM lung metastasis in
      nude mice. This result indicated that PAF acts as a promoter of melanoma
      metastasis in vivo. We proposed that metastatic melanoma cells overexpressing
      CREB/ATF-1 are better equipped than nonmetastatic cells to respond to PAF within
      the tumor microenvironment.

PMID- 16306051
TI  - Substitution of the N-glycan function in glycosyltransferases by specific amino
      acids: ST3Gal-V as a model enzyme.
AB  - The sialyltranferase ST3Gal-V transfers a sialic acid to lactosylceramide. We
      investigated the role of each of the N-glycans modifying mouse ST3Gal-V (mST3Gal
      V) by measuring the in vitro enzyme activity of Chinese hamster ovary (CHO) cells
      transfected with ST3Gal-V cDNA or its mutants. By examining mutants of mST3Gal-V,
      in which each asparagine was replaced with glutamine (N180Q, N224Q, N334Q), we
      determined that all three sites are N-glycosylated and that each N-glycan is
      required for enzyme activity. Despite their importance, N-glycosylation sites in
      ST3Gal-V are not conserved among species. Therefore, we considered whether the
      function in the activity that is performed in mST3Gal-V by the N-glycan could be
      substituted for by specific amino acid residues selected from the ST3Gal-V of
      other species or from related sialyltransferases (ST3Gal-I, -II, -III, and -IV),
      placed at or near the glycosylation sites. To this end, we constructed a series
      of interspecies mutants for mST3Gal-V, specifically, mST3Gal-V-H177D-N180S
      (medaka or tetraodon type), mST3Gal-V-N224K (human type), and mST3Gal-V-T336Q
      (zebrafish type). The ST3Gal-V activity of these mutants was quite similar to
      that of the wild-type enzyme. Thus, we have demonstrated here that the N-glycans
      on mST3Gal-V are required for activity but can be substituted for specific amino
      acid residues placed at or near the glycosylation sites. We named this method
      SUNGA (substitution of N-glycan functions in glycosyltransferases by specific
      amino acids). Furthermore, we verified that the ST3Gal-V mutant created using the
      SUNGA method maintains its high activity when expressed in Escherichia coli
      thereby establishing the usefulness of the SUNGA method in exploring the function
      of N-glycans in vivo.

PMID- 16306052
TI  - Pathophysiology of oxygen delivery in respiratory failure.
AB  - Complex physiologic interactions exist between oxygenation, hemoglobin, and
      cardiac output (Qt) in critically ill patients with respiratory failure. When any
      or all of these three critical factors fail, clinicians are challenged to support
      oxygen delivery (DO(2)) in order to avoid tissue hypoxia, end-organ damage, and
      high mortality rates. Many of the interventions performed to improve DO(2),
      including mechanical ventilation, blood transfusions, fluid management, and
      invasive monitoring of cardiac function, are accompanied by serious risks that
      can exacerbate the pathology of DO(2). This article provides an overview of
      oxygenation, hemoglobin, and Qt in patients with respiratory failure and
      highlights some of the current research that seeks safe and effective ways to
      improve DO(2) in these patients.

PMID- 16306053
TI  - Monitoring oxygen delivery in the critically ill.
AB  - An accurate assessment of regional tissue oxygen delivery (DO(2)) may help the
      intensivist to attenuate end-organ damage in critically ill patients. Transport
      of oxygen from the ambient air to the mitochondria occurs by convection and
      diffusion, and is tightly regulated by neural and humoral factors. This article
      reviews the basic principles of DO(2) and the abnormal oxygen supply-demand
      relationship seen in patients with shock. It also discusses approaches to
      monitoring DO(2), including clinical symptoms/signs, acid-base status, and gas
      exchange, which provide global assessment, as well as gastric tonometry, which
      may reflect regional DO(2). Some new experimental methods, such as near-infrared
      spectroscopy and positron emission tomography, are still in development but may
      in the future provide useful clinical devices for quantifying the adequacy of
      regional tissue oxygenation in critically ill patients.

PMID- 16306054
TI  - Current issues in mechanical ventilation for respiratory failure.
AB  - The morbidity and mortality associated with respiratory failure is, to a certain
      extent, iatrogenic. Mechanical ventilation, although the mainstay of treatment
      for respiratory distress syndrome, can result in physical trauma to lung tissue
      (ventilator-induced lung injury [VILI]). Strategies to alleviate VILI are often
      termed lung-protective strategies and are aimed at reducing overstretching and
      shear stresses associated with repetitive alveolar collapse and reopening. Lower
      tidal volumes during ventilation, maintenance of positive-end expiratory
      pressure, and high-frequency ventilation are the best-studied lung-protective
      strategies that appear to reduce VILI. Faster withdrawal from mechanical
      ventilation could also improve outcomes and lower the costs associated with care.
      To enhance the success of weaning from mechanical ventilation, the cooperative
      efforts of physicians and respiratory therapists are needed. These efforts
      involve the initiation of spontaneous-breathing trials, implementation of
      systematic weaning protocols, and optimization of individual patient
      interventions.

PMID- 16306055
TI  - Anemia in the long-term ventilator-dependent patient with respiratory failure.
AB  - Anemia occurs in virtually all critically ill patients receiving long-term
      mechanical ventilation and has been associated with increased mortality and poor
      outcomes. Allogeneic RBC transfusions are routinely administered to critically
      ill anemic patients, especially during lengthy stays in ICUs or in long-term
      acute care facilities. Although RBC transfusions are a physiologically rational
      approach to raising hemoglobin levels, they may increase the risk of
      complications and have been associated with higher mortality in critically ill
      patients. Treatment with epoetin alfa, an erythropoiesis-stimulating agent, as a
      means of reducing transfusion requirements has been studied in the critically ill
      and in patients receiving long-term mechanical ventilation. Promising results
      have been reported, including a potential survival benefit, although larger and
      more definitive studies are needed in order to establish whether raising
      hemoglobin levels affects clinical outcomes in patients receiving mechanical
      ventilation.

PMID- 16306056
TI  - The impact of anemia in patients with respiratory failure.
AB  - Healthy individuals are able to tolerate profound, short-term decreases in
      hemoglobin levels and oxygen saturation without serious consequences, but
      critically ill patients in respiratory failure lack the necessary reserve
      capacity to preserve tissue oxygenation. The development of progressive anemia in
      ICU patients has led to much interest and debate about transfusion practices, yet
      optimal hemoglobin levels and how they should be achieved remain unclear. Animal
      and human studies regarding critical oxygen delivery provide the rationale for
      optimizing hemoglobin levels and supporting cardiovascular function during
      respiratory failure. Theoretically, the oxygen-carrying benefit of RBCs should
      hasten recovery from respiratory failure, and transfusions would therefore be
      expected to shorten the duration of mechanical ventilation. However, evidence to
      the contrary has been reported. Controversies related to transfusions and their
      inability to improve outcomes suggest that further research regarding transfusion
      alternatives is needed, especially in anemic patients with respiratory failure.

PMID- 16306057
TI  - Ventilator-associated pneumonia: insights from recent clinical trials.
AB  - Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in
      the ICU and contributes disproportionately to both poor outcomes and the high
      cost of care in critically ill patients. While VAP has been the focus of
      extensive research, little consensus exists about methods for diagnosis,
      treatment, or prevention. Delays in initiating appropriate therapy, antibiotic
      resistance due to indiscriminate and prolonged use of broad-spectrum antibiotics,
      and treatment of patients with a low risk of VAP (based on clinical pulmonary
      infection scores) represent a sample of VAP-related issues that have been
      addressed in recent clinical trials. Educational programs for VAP prevention and
      other nonpharmacologic strategies aimed at eliminating VAP have also been
      explored in clinical investigations. This review highlights selected areas of new
      clinical research on VAP treatment and prevention in order to place their
      significance in context.

PMID- 16306058
TI  - Cardiovascular issues in respiratory care.
AB  - The hemodynamic effects of ventilation are complex but can be grouped under four
      clinically relevant concepts. First, spontaneous ventilation is exercise, and
      critically ill patients may not withstand the increased work of breathing.
      Initiation of mechanical ventilatory support will improve oxygen delivery to the
      remainder of the body by decreasing oxygen consumption. To the extent that mixed
      venous oxygen also increases, Pao(2) will increase without any improvement in gas
      exchange. Similarly, weaning from mechanical ventilatory support is a
      cardiovascular stress test. Patients who fail to wean also manifest
      cardiovascular insufficiency during the failed weaning attempts. Improving
      cardiovascular reserve or supplementing support with inotropic therapy may allow
      patients to wean from mechanical ventilation. Second, changes in lung volume
      alter autonomic tone and pulmonary vascular resistance (PVR), and at high lung
      volumes compress the heart in the cardiac fossa. Hyperinflation increases PVR and
      pulmonary artery pressure, impeding right ventricular ejection. Decreases in lung
      volume induce alveolar collapse and hypoxia, stimulating an increased pulmonary
      vasomotor tone by the process of hypoxic pulmonary vasoconstriction. Recruitment
      maneuvers, positive end-expiratory pressure, and continuous positive airway
      pressure may reverse hypoxic pulmonary vasoconstriction and reduce pulmonary
      artery pressure. Third, spontaneous inspiration and spontaneous inspiratory
      efforts decrease intrathoracic pressure (ITP). Since diaphragmatic descent
      increases intra-abdominal pressure, these combined effects cause right atrial
      pressure inside the thorax to decrease but venous pressure in the abdomen to
      increase, markedly increasing the pressure gradient for systemic venous return.
      Furthermore, the greater the decrease in ITP, the greater the increase in left
      ventricular (LV) afterload for a constant arterial pressure. Mechanical
      ventilation, by abolishing the negative swings in ITP, will selectively decrease
      LV afterload, as long as the increases in lung volume and ITP are small. Finally,
      positive-pressure ventilation increases ITP. Since diaphragmatic descent
      increases intra-abdominal pressure, the decrease in the pressure gradient for
      venous return is less than would otherwise occur if the only change were an
      increase in right atrial pressure. However, in hypovolemic states, positive
      pressure ventilation can induce profound decreases in venous return. Increases in
      ITP decrease LV afterload and will augment LV ejection. In patients with
      hypervolemic heart failure, this afterload reducing effect can result in improved
      LV ejection, increased cardiac output, and reduced myocardial oxygen demand.

PMID- 16306059
TI  - Understanding the consequences of transfusion-related acute lung injury.
AB  - Although the blood supply has become safer with regard to transmission of
      infectious agents, attention should continue to focus on understanding and
      eliminating the other serious risks associated with transfusion. Transfusion
      related acute lung injury (TRALI) is one such risk, only recently becoming
      recognized as an important and potentially preventable clinical syndrome.
      Strategies for prevention of TRALI, however, must rely on knowledge regarding its
      etiology and diagnosis, and significant gaps in our understanding of the syndrome
      currently exist. This review summarizes what is known and unknown about the
      incidence, severity, etiology, diagnosis, and prevention of TRALI and the
      potential consequences of these knowledge gaps.

PMID- 16306061
TI  - EUI1, encoding a putative cytochrome P450 monooxygenase, regulates internode
      elongation by modulating gibberellin responses in rice.
AB  - Elongation of rice internodes is one of the most important agronomic traits,
      which determines the plant height and underlies the grain yield. It has been
      shown that the elongation of internodes is under genetic control, and various
      factors are implicated in the process. Here, we report a detailed
      characterization of an elongated uppermost internode1 (eui1) mutant, which has
      been used in hybrid rice breeding. In the eui1-2 mutant, the cell lengths in the
      uppermost internodes are significantly longer than that of wild type and thus
      give rise to the elongated uppermost internode. It was found that the level of
      active gibberellin was elevated in the mutant, whereas its growth in response to
      gibberellin is similar to that of the wild type, suggesting that the higher level
      accumulation of gibberellin in the eui1 mutant causes the abnormal elongation of
      the uppermost internode. Consistently, the expression levels of several genes
      which encode gibberellin biosynthesis enzymes were altered. We cloned the EUI1
      gene, which encodes a putative cytochrome P450 monooxygenase, by map-based
      cloning and found that EUI1 was weakly expressed in most tissues, but
      preferentially in young panicles. To confirm its function, transgenic experiments
      with different constructs of EUI1 were conducted. Overexpression of EUI1 gave
      rise to the gibberellin-deficient-like phenotypes, which could be partially
      reversed by supplementation with gibberellin. Furthermore, apart from the
      alteration of expression levels of the gibberellin biosynthesis genes,
      accumulation of SLR1 protein was found in the overexpressing transgenic plants,
      indicating that the expression level of EUI1 is implicated in both gibberellin
      mediated SLR1 destruction and a feedback regulation in gibberellin biosynthesis.
      Therefore, we proposed that EUI1 plays a negative role in gibberellin-mediated
      regulation of cell elongation in the uppermost internode of rice.

PMID- 16306060
TI  - Randomised study of effect of different doses of vitamin A on childhood morbidity
      and mortality.
AB  - OBJECTIVES: To determine whether the dose of vitamin A currently recommended by
      the World Health Organization or half this dose gives better protection against
      childhood morbidity and mortality. DESIGN: Randomised study. SETTING: A combined
      oral polio vaccine and vitamin A supplementation campaign in Guinea-Bissau,
      Africa. PARTICIPANTS: 4983 children aged 6 months to 5 years. INTERVENTIONS: One
      of two doses of vitamin A (recommended and half); oral polio vaccine. MAIN
      OUTCOME MEASURES: Mortality and morbidity at six and nine months. RESULTS:
      Mortality was lower in the children who took half the recommended dose of vitamin
      A compared with the full dose at both six months (mortality rate ratio 0.69, 95%
      confidence interval 0.36 to 1.35) and nine months (0.62, 0.36 to 1.06) of follow
      up. There was a significant interaction between sex and dose, the lower dose
      being associated with significantly reduced mortality in girls (0.19, 0.06 to
      0.66) but not in boys (1.98, 0.74 to 5.29). The lower dose of vitamin A was
      consistently associated with lower hospital case fatality in girls (0.19, 0.02 to
      1.45). Paradoxically, in children aged 6-18 months, the low dose was associated
      with slightly higher morbidity. CONCLUSIONS: Half the dose of vitamin A currently
      recommended by WHO may provide equally good or better protection against
      mortality but not against morbidity.

PMID- 16306062
TI  - AtVAM3 is required for normal specification of idioblasts, myrosin cells.
AB  - Myrosin cells in Capparales plants are idioblasts that accumulate thioglucoside
      glucohydrolase (TGG, also called myrosinase), which hydrolyzes glucosinolates to
      produce toxic compounds for repelling pests. Here, we show that AtVAM3 is
      involved in development of myrosin cells. It has been shown that yeast VAM3 is a
      Q(a)-SNARE that is involved in vesicle transport of vacuolar proteins and
      vacuolar assembly. We found that two Arabidopsis atvam3 alleles, atvam3-3 and
      atvam3-4/ssm, accumulate large amounts of TGG1 and TGG2 that are enzymatically
      active. An immunogold analysis revealed that TGGs were specifically localized in
      the vacuole of myrosin cells in atvam3 mutants. This result indicates that TGGs
      are normally transported to vacuoles in these mutants and that AtVAM3 is not
      essential for vacuolar transport of the proteins. We developed a staining method
      with Coomassie brilliant blue that detects myrosin cells in whole leaves by their
      high TGG content. This method showed that atvam3 leaves have a larger number of
      myrosin cells than do wild-type leaves. Myrosin cells were scattered along leaf
      veins in wild-type leaves, while they were abnormally distributed in atvam3
      leaves. The mutants developed a network of myrosin cells throughout the leaves:
      myrosin cells were not only distributed continuously along leaf veins, but were
      also observed independent of leaf veins. The excess of myrosin cells in atvam3
      mutants might be responsible for the abnormal abundance of TGGs and the reduction
      of elongation of inflorescence stems and leaves in these mutants. Our results
      suggest that AtVAM3 has a plant-specific function in development of myrosin
      cells.

PMID- 16306063
TI  - Common pathological mechanisms in mouse models for muscular dystrophies.
AB  - Duchenne/Becker and limb-girdle muscular dystrophies share clinical symptoms like
      muscle weakness and wasting but differ in clinical presentation and severity. To
      get a closer view on the differentiating molecular events responsible for the
      muscular dystrophies, we have carried out a comparative gene expression profiling
      of hindlimb muscles of the following mouse models: dystrophin-deficient (mdx,
      mdx(3cv)), sarcoglycan-deficient (Sgca null, Sgcb null, Sgcg null, Sgcd null),
      dysferlin-deficient (Dysf null, SJL(Dysf)), sarcospan-deficient (Sspn null), and
      wild-type (C57Bl/6, C57Bl/10) mice. The expression profiles clearly discriminated
      between severely affected (dystrophinopathies and sarcoglycanopathies) and mildly
      or nonaffected models (dysferlinopathies, sarcospan-deficiency, wild-type).
      Dystrophin-deficient and sarcoglycan-deficient profiles were remarkably similar,
      sharing inflammatory and structural remodeling processes. These processes were
      also ongoing in dysferlin-deficient animals, albeit at lower levels, in agreement
      with the later age of onset of this muscular dystrophy. The inflammatory proteins
      Spp1 and S100a9 were up-regulated in all models, including sarcospan-deficient
      mice, which points, for the first time, at a subtle phenotype for Sspn null mice.
      In conclusion, we identified biomarker genes for which expression correlates with
      the severity of the disease, which can be used for monitoring disease
      progression. This comparative study is an integrating step toward the development
      of an expression profiling-based diagnostic approach for muscular dystrophies in
      humans.

PMID- 16306064
TI  - The health service coverage of quality-certified primary health care units in
      Metro-Manila, the Philippines.
AB  - INTRODUCTION: In 1998, the Philippines' Department of Health implemented the
      Quality Assurance Programme, known as the Sentrong Sigla (Centre of Vitality)
      Movement, starting with primary health care units. The Department established the
      National Objectives for Health in 1999, which set targets for health status and
      service coverage by 2004. The Movement certifies primary health care facilities
      that comply with its list of quality standards. Three years after implementation
      of the Sentrong Sigla Movement, the present study assessed it as an intervention
      for the delivery of health care services. Specifically, it evaluated the 2001
      service coverage among certified facilities and compared it with that of non
      certified facilities in the National Capital Region (Metro-Manila) of the
      Philippines, and related service coverage to the targets of the National
      Objectives for Health for 2001. METHODS: For the intervention group, the study
      randomly selected 82 of the 143 certified facilities (57.3%), with 88 of the 223
      non-certified facilities (39.5%) serving as the control group. Using reliable and
      valid measurement indicator tools, data were collected on preventive health
      services programmes, curative programmes and monitoring programmes. To compare
      service coverage of the intervention and control groups, the data were analyzed
      using chi-squared tests, prevalence ratios, clustered sampling analysis and
      linear regressions of the rates. RESULTS: The overall 2001 service coverage shows
      that certified facilities had significantly less success in the preventive and
      monitoring programmes than the non-certified facilities, but were not
      significantly different in the curative programmes. Neither type of facility
      reached the targets of the 2001 National Objectives for Health for preventive
      programmes. After adjusting for clustering, the certified facilities showed
      significantly lower service coverage, compared with non-certified facilities,
      only for enrolling new acceptors to the Family Planning Programme and for water
      supply testing in the Environmental Sanitation Programme. CONCLUSION: Unlike
      previous studies, the results and analysis of the present study show that,
      generally, the Sentrong Sigla Movement had not improved the processes required to
      achieve better outcomes. Factors that could have contributed to the findings are
      described and strategies for improvement are recommended.

PMID- 16306066
TI  - Context matters: interpreting impact findings in child survival evaluations.
AB  - Appropriate consideration of contextual factors is essential for ensuring
      internal and external validity of randomized and non-randomized evaluations.
      Contextual factors may confound the association between delivery of the
      intervention and its potential health impact. They may also modify the effect of
      the intervention or programme, thus affecting the generalizability of results.
      This is particularly true for large-scale health programmes, for which impact may
      vary substantially from one context to another. Understanding the nature and role
      of contextual factors may improve the validity of study results, as well as help
      predict programme impact across sites. This paper describes the experience
      acquired in measuring and accounting for contextual factors in the Multi-Country
      Evaluation of the IMCI (Integrated Management of Childhood Illness) strategy in
      five countries: Bangladesh, Brazil, Peru, Uganda and Tanzania. Two main types of
      contextual factors were identified. Implementation-related factors include the
      characteristics of the health systems where IMCI was implemented, such as
      utilization rates, basic skills of health workers, and availability of drugs,
      supervision and referral. Impact-related factors include baseline levels and
      patterns of child mortality and nutritional status, which affect the scope for
      programme impact. We describe the strategies used in the IMCI evaluation in order
      to obtain data on relevant contextual factors and to incorporate them in the
      analyses. Two case studies - from Tanzania and Peru - show how appropriate
      consideration of contextual factors may help explain apparently conflicting
      evaluation results.

PMID- 16306067
TI  - Implementation of the Integrated Management of Childhood Illness strategy in Peru
      and its association with health indicators: an ecological analysis.
AB  - The Multi-Country Evaluation of Integrated Management of Childhood Illness (IMCI)
      Effectiveness, Cost and Impact (MCE) was launched to assess the global
      effectiveness of this strategy. Impact evaluations were started in five
      countries. The objectives of the Peru MCE were: (1) to document trends in IMCI
      implementation in the 24 departments of Peru from 1996 to 2000; (2) to document
      trends in indicators of health services coverage and impact (mortality and
      nutritional status) for the same period; (3) to correlate changes in these two
      sets of indicators, and (4) to attempt to rule out contextual factors that may
      affect the observed trends and correlations. An ecological analysis was performed
      in which the units of study were the 24 departments. By 2000, 10.2% of clinical
      health workers were trained in IMCI, but some districts showed considerably
      higher rates. There were no significant associations between clinical IMCI
      training coverage and indicators of outpatient utilization, vaccine coverage,
      mortality or malnutrition. The lack of association persisted after adjustment for
      several contextual factors including socioeconomic and environmental indicators
      and the presence of other child health projects. Community health workers were
      also trained in IMCI, and training coverage was not associated with any of the
      process or impact indicators, except for a significant positive correlation with
      mean height for age. According to the MCE impact model, IMCI implementation must
      be sufficiently strong to lead to an impact on health and nutrition. Health
      systems support for IMCI implementation in Peru was far from adequate. This
      finding, along with low training coverage level and a relatively low child
      mortality rate, may explain why the expected impact was not documented.
      Nevertheless, even districts with high levels of training coverage failed to show
      an impact. Further national effectiveness studies of IMCI and other child
      interventions are warranted as these interventions are scaled up.

PMID- 16306068
TI  - Impact of IMCI health worker training on routinely collected child health
      indicators in Northeast Brazil.
AB  - The Integrated Management of Childhood Illness (IMCI) is a global strategy
      including improvements in case management at health facilities, strengthening
      health systems support and improving key family and community practices relevant
      to child health. In Brazil, IMCI was introduced in 1997, being largely restricted
      to training health workers in case management. IMCI training of doctors and
      nurses took place in many municipalities, but implementation of the other two
      components of IMCI was very limited. We analyze the impact of IMCI health worker
      training on infant mortality in three states in north-eastern Brazil, by
      comparing three groups of municipalities over the period 1999 to 2002: 23 with
      training coverage of 50% or greater, 216 with lower training coverage, and 204
      without any IMCI training. Two sources of mortality data are used: vital
      registration of deaths and births, and the community health workers' (CHW)
      demographic surveillance system. The latter resulted in a larger number of deaths
      being reported and in more stable mortality rates over time than the former.
      Infant mortality rates (IMR) declined rapidly according to both sources of
      information, during the study period. After adjustment for confounding factors,
      there was no association between IMCI training coverage and infant mortality
      measured through either information system. According to the CHW data, the
      adjusted annual changes were of -7.2 deaths per 1,000 births in the high IMCI
      training coverage group, -4.6 in the low IMCI training coverage and -5.0 in the
      no IMCI group (p=0.46). According to vital statistics, the corresponding average
      annual changes were -5.0, -4.2 and -2.8 deaths per 1,000 births (p=0.16). The
      negative findings from the Brazil evaluation suggest that IMCI clinical training,
      in the absence of the other two components of IMCI, and in an area with infant
      mortality under 50 per 1,000, is unlikely to lead to a measurable impact on
      mortality.

PMID- 16306069
TI  - Capacity constraints to the adoption of new interventions: consultation time and
      the Integrated Management of Childhood Illness in Brazil.
AB  - Information on how health workers spend their time can help programme managers
      determine whether it is possible to add new services or activities to their
      schedules and at what cost. One set of interventions with the potential to reduce
      under-five mortality is training of facility-based health workers according to
      the guidelines for Integrated Management of Childhood Illness (IMCI), along with
      improvements to supervision, procurement and information systems that are part of
      the IMCI strategy. Although it has been shown that IMCI is associated with
      improved quality of care, it is important to determine if it also requires
      additional consultation time. To investigate the amount of time required to
      provide clinical care to children under 5 years based on IMCI compared with
      routine care, a time and motion study was conducted in Northeast Brazil. IMCI
      trained providers spent 1 minute and 26 seconds longer per consultation with
      under-fives than untrained providers, holding confounding factors constant at the
      mean levels observed in the sample. The difference was greater when patient load
      was low, and decreased as the number of patients a provider saw per day
      increased. This has three implications. First, the ability of the system to
      absorb new technologies depends on current capacity utilization. Secondly, the
      cost of treating a child also depends on the level of capacity utilization, at
      least in terms of provider time. Thirdly, where patient loads are high it is
      important to determine if the quality of care required for IMCI can be
      maintained.

PMID- 16306070
TI  - Programmatic pathways to child survival: results of a multi-country evaluation of
      Integrated Management of Childhood Illness.
AB  - OBJECTIVE: To summarize the expectations held by World Health Organization
      programme personnel about how the introduction of the Integrated Management of
      Childhood Illness (IMCI) strategy would lead to improvements in child health and
      nutrition, to compare these expectations with what was learned from the Multi
      Country Evaluation of IMCI Effectiveness, Cost and Impact (MCE-IMCI), and to
      discuss the implications of these findings for child survival policies and
      programmes. DESIGN: The MCE-IMCI study designs were based on an impact model
      developed in 1999-2000 to define how IMCI would be implemented at country level
      and below, and the outcomes and impact it would have on child health and
      survival. MCE-IMCI studies included: feasibility assessments documenting IMCI
      implementation in 12 countries (1999-2001); in-depth studies using compatible
      designs in Bangladesh, Brazil, Peru, Tanzania and Uganda; and cross-site analyses
      addressing the effectiveness of specific subsets of IMCI activities. RESULTS: The
      IMCI strategy was successfully introduced in the great majority of countries with
      moderate to high levels of child mortality in the period from 1996 to 2001. Seven
      years of country-based evaluation, however, indicates that some of the basic
      expectations underlying the development of IMCI were not met. Four of the five
      countries (the exception is Tanzania) had difficulties in expanding the strategy
      at national level while maintaining adequate intervention quality. Technical
      guidelines on delivering interventions at family and community levels were slow
      to appear, and in their absence countries stalled in their efforts to increase
      population coverage with essential interventions related to care-seeking,
      nutrition, and correct care of the sick child at home. The full weight of health
      system limitations on IMCI implementation was not appreciated at the outset, and
      only now is it clear that solutions to larger problems in political commitment,
      human resources, financing, integrated or at least coordinated programme
      management, and effective decentralization are essential underpinnings of
      successful efforts to reduce child mortality. CONCLUSIONS: This analysis
      highlights the need for a shift if child survival efforts are to be successful.
      Delivery systems that rely solely on government health facilities must be
      expanded to include the full range of potential channels in a setting and strong
      community-based approaches. The focus on process within child health programmes
      must change to include greater accountability for intervention coverage at
      population level. Global strategies that expect countries to make massive
      adaptations must be complemented by country-level implementation guidelines that
      begin with local epidemiology and rely on tools developed for specific
      epidemiological profiles.

PMID- 16306071
TI  - Improving facility-based care for sick children in Uganda: training is not
      enough.
AB  - This study assessed the effects of scaling-up Integrated Management of Childhood
      Illness (IMCI) on the quality of care received by sick children in 10 districts
      in Uganda. Health workers trained in IMCI were found to deliver significantly
      better care than health workers who had not yet been trained, but absolute levels
      of service quality remained low. Achieving training coverage alone is not
      sufficient as a strategy to improve and sustain care quality. Other factors
      including training quality, effective supervision, availability of essential
      drugs, vaccines and equipment, and the policy context are also important and must
      be included in child survival policies and plans.

PMID- 16306072
TI  - Improving quality and efficiency of facility-based child health care through
      Integrated Management of Childhood Illness in Tanzania.
AB  - OBJECTIVES: To assess the effect of Integrated Management of Childhood Illness
      (IMCI) relative to routine care on the quality and efficiency of providing care
      for sick children in first-level health facilities in Tanzania, and to
      disseminate the results for use in health sector decision-making. DESIGN: Non
      randomized controlled trial to compare child health care quality and economic
      costs in two intervention (>90% of health care workers trained in IMCI) and two
      comparison districts in rural Tanzania. PARTICIPANTS: For quality measures, all
      sick children presenting for care at random samples of first-level health
      facilities; for costs, all national, district, facility and household costs
      associated with child health care, taking a societal perspective. RESULTS: IMCI
      training is associated with significantly better child health care in facilities
      at no additional cost to districts. The cost per child visit managed correctly
      was lower in IMCI than in routine care settings: $4.02 versus $25.70,
      respectively, in 1999 US dollars and after standardization for variations in
      population size. CONCLUSION: IMCI improved the quality and efficiency of child
      health care relative to routine child health care in the study districts.
      Previous study results indicated that the introduction of IMCI in these Tanzanian
      districts was associated with mortality levels that were 13% lower than in
      comparison districts. We can therefore conclude that IMCI is also more cost
      effective than routine care for improving child health outcomes. The
      dissemination strategy for these results led to adoption of IMCI for nationwide
      implementation within 12 months of study completion.

PMID- 16306073
TI  - Impact of Integrated Management of Childhood Illness on inequalities in child
      health in rural Tanzania.
AB  - We examined the impact of the Integrated Management of Childhood Illness (IMCI)
      strategy on the equality of health outcomes and access across socioeconomic
      gradients in rural Tanzania, by comparing changes in inequities between 1999 and
      2002 in two districts with IMCI (Morogoro Rural and Rufiji) and two without
      (Kilombero and Ulanga). Equity differentials for six child health indicators
      (underweight, stunting, measles immunization, access to treated and untreated
      nets, treatment of fever with antimalarial) improved significantly in IMCI
      districts compared with comparison districts (p<0.05), while four indicators
      (wasting, DPT coverage, caretakers' knowledge of danger signs and appropriate
      careseeking) improved significantly in comparison districts compared with IMCI
      districts (p<0.05). The largest improvements were observed for stunting among
      children between 24-59 months of age. The concentration index improved from 
      0.102 in 1999 to -0.032 in 2002 for IMCI, while it remained almost unchanged 
      0.122 to -0.133 in comparison districts. IMCI was associated with improved equity
      for measles vaccine coverage, whereas the opposite was observed for DPT antigens.
      This study has shown how equity assessments can be incorporated in impact
      evaluation at relatively little additional cost, and how this may point to
      specific interventions that need to be reinforced. The introduction of IMCI led
      to improvements in child health that did not occur at the expense of equity.

PMID- 16306074
TI  - Out-of-pocket payments for under-five health care in rural southern Tanzania.
AB  - Catastrophic payments and fairness in financial contributions for health care are
      becoming increasing concerns for many governments. Out-of-pocket financing for
      health care is common in many developing countries, including Tanzania. As part
      of the Multi-Country Evaluation of the Integrated Management of Childhood Illness
      (MCE-IMCI), the objective of this paper is to explore the determinants of
      variation and the level of out-of-pocket payments for child health care in rural
      Tanzania, with and without IMCI, using data from two household surveys conducted
      in 1999 and 2002. We analyzed data for 833 visits to health providers for 764
      children who had been sick in the 2 weeks prior to the survey and who had sought
      care at a 'Western' or formal health care provider. We found evidence that IMCI
      was associated with lower out-of-pocket costs at government facilities (Tshs.3.5
      compared with Tshs.6.9 without IMCI) and in NGOs (Tshs.95.1 compared with
      Tshs.267.3). Out-of-pocket payments were on average Tshs.110.1 when care was
      sought at government primary health care facilities running a cost-sharing
      scheme, about 15 times higher than in those not part of the scheme (p<0.0001).
      Those who visited NGO facilities paid about 30 times more than those seeking care
      at government facilities not operating the cost-sharing scheme (p<0.0001). In
      conclusion, there is no doubt that health care financing mechanisms and equitable
      access to government facilities have a major impact on household economic burden
      related to under-five illness. Increasing access to IMCI-based care, however,
      offers an additional opportunity to reduce out-of-pocket payments, mainly through
      more rational use of medicines. Increasing access to IMCI-based care would not
      only improve inequities in financial contributions, but also in health, an
      important consideration for its own sake.

PMID- 16306075
TI  - Ten methodological lessons from the multi-country evaluation of integrated
      Management of Childhood Illness.
AB  - OBJECTIVE: To describe key methodological aspects of the Multi-Country Evaluation
      of the Integrated Management of Childhood Illness strategy (MCE-IMCI) and analyze
      their implications for other public health impact evaluations. DESIGN: The MCE
      IMCI evaluation designs are based on an impact model that defined expectations in
      the late 1990s about how IMCI would be implemented at country level and below,
      and the outcomes and impact it would have on child health and survival. MCE-IMCI
      studies include: feasibility assessments documenting IMCI implementation in 12
      countries; in-depth studies using compatible designs in five countries; and cross
      site analyses addressing the effectiveness of specific subsets of IMCI
      activities. The MCE-IMCI was designed to evaluate the impact of IMCI, and also to
      see that the findings from the evaluation were taken up through formal feedback
      sessions at national, sub-national and local levels. RESULTS: Issues that arose
      early in the MCE-IMCI included: (1) defining the scope of the evaluation; (2)
      selecting study sites and developing research designs; (3) protecting
      objectivity; and (4) developing an impact model. Issues that arose mid-course
      included: (5) anticipating and addressing problems with external validity; (6)
      ensuring an appropriate time frame for the full evaluation cycle; (7) providing
      feedback on results to policymakers and programme implementers; and (8) modifying
      site-specific designs in response to early findings about the patterns and pace
      of programme implementation. Two critical issues could best be addressed only
      near the close of the evaluation: (9) factors affecting the uptake of evaluation
      results by policymakers and programme decision makers; and (10) the costs of the
      evaluation. CONCLUSIONS: Large-scale effectiveness evaluations present challenges
      that have not been addressed fully in the methodological literature. Although
      some of these challenges are context-specific, there are important lessons from
      the MCE that can inform future designs. Most of the issues described here are not
      addressed explicitly in research reports or evaluation textbooks. Describing and
      analyzing these experiences is one way to promote improved impact evaluations of
      new global health strategies.

PMID- 16306076
TI  - The loss of the chloride channel, ClC-5, delays apical iodide efflux and induces
      a euthyroid goiter in the mouse thyroid gland.
AB  - Genetic inactivation of ClC-5, a voltage-gated chloride channel prominently
      expressed in the kidney, leads to proteinuria because of defective apical
      endocytosis in proximal tubular cells. Because thyroid hormone secretion depends
      on apical endocytosis of thyroglobulin (Tg), we investigated whether ClC-5 is
      expressed in the thyroid and affects its function, using Clcn5-deficient knockout
      (KO) mice. We found that ClC-5 is highly expressed in wild-type mouse thyroid (
      approximately 40% of mRNA kidney level). The protein was immunolocalized at the
      apical pole of thyrocytes. In Percoll gradients, ClC-5 overlapped with plasma
      membrane and early endosome markers, but best codistributed with the late
      endosomal marker, Rab7. ClC-5 KO mice were euthyroid (normal T4 and TSH serum
      levels) but developed a goiter with parallel iodine and Tg accumulation (i.e.
      normal Tg iodination level). When comparing ClC-5 KO with wild-type mice, thyroid
      125I uptake after 1 h was doubled, incorporation into Tg was decreased by
      approximately 2-fold, so that trichloroacetic acid-soluble 125I increased
      approximately 4-fold. Enhanced 125I- efflux upon perchlorate and presence of 125I
      Tg as autoradiographic rings at follicle periphery demonstrated delayed iodide
      organification. Endocytic trafficking of 125I-Tg toward lysosomes was not
      inhibited. Expression of pendrin, an I-/Cl- exchanger involved in apical iodide
      efflux, was selectively decreased by 60% in KO mice at mRNA and protein levels.
      Thus, ClC-5 is well expressed in the thyroid but is not critical for apical
      endocytosis, contrary to the kidney. Instead, the goiter associated with ClC-5 KO
      results from impaired rate of apical iodide efflux by down-regulation of pendrin
      expression.

PMID- 16306077
TI  - Recruitment of the tyrosine phosphatase Src homology 2 domain tyrosine
      phosphatase-2 to the p85 subunit of phosphatidylinositol-3 (PI-3) kinase is
      required for insulin-like growth factor-I-dependent PI-3 kinase activation in
      smooth muscle cells.
AB  - IGF-I stimulates smooth muscle cell (SMC) migration and the phosphatidylinositol
      3 (PI-3) kinase pathway plays an important role in mediating the IGF-I-induced
      migratory response. Prior studies have shown that the tyrosine phosphatase Src
      homology 2 domain tyrosine phosphatase (SHP)-2 is necessary to activate PI-3
      kinase in response to growth factors and expression of a phosphatase inactive
      form of SHP-2 (SHP-2/C459S) impairs IGF-I-stimulated cell migration. However, the
      mechanism by which SHP-2 phosphatase activity or the recruitment of SHP-2 to
      other signaling molecules contributes to IGF-I stimulated PI-3 kinase activation
      has not been determined. SMCs that had stable expression of SHP-2/C459S had
      reduced cell migration and Akt activation in response to IGF-I, compared with SMC
      expressing native SHP-2. Similarly in cells expressing native SHP-2, IGF-I
      induced SHP-2 binding to p85, whereas in cells expressing SHP-2/C459S, there was
      no increase. Because the C459S substitution results in loss of the ability of SHP
      2 to disassociate from its substrates, making it inaccessible not only to p85 but
      also the other proteins, a p85 mutant in which tyrosines 528 and 556 were changed
      to phenylalanines was prepared to determine whether this would disrupt the
      p85/SHP-2 interaction and whether the loss of this specific interaction would
      alter IGF-I stimulated the cell migration. Substitution for these tyrosines in
      p85 resulted in loss of SHP-2 recruitment and was associated with a reduction in
      association of the p85/p110 complex with insulin receptor substrate-1. Cells
      stably expressing this p85 mutant also showed a decrease in IGF-I-stimulated PI-3
      kinase activity and cell migration. Preincubation of cells with a cell-permeable
      peptide that contains the tyrosine556 motif of p85 also disrupted SHP-2 binding
      to p85 and inhibited the IGF-I-induced increase in cell migration. The findings
      indicate that tyrosines 528 and 556 in p85 are required for SHP-2 association.
      SHP-2 recruitment to p85 is required for IGF-I-stimulated association of the
      p85/p110 complex with insulin receptor substrate-1 and for the subsequent
      activation of the PI-3 kinase pathway leading to increased cell migration.

PMID- 16306078
TI  - Cyclic adenosine 5'-monophosphate-dependent sphingosine-1-phosphate biosynthesis
      induces human CYP17 gene transcription by activating cleavage of sterol
      regulatory element binding protein 1.
AB  - In the human adrenal cortex, ACTH activates steroid hormone biosynthesis by
      acutely increasing cholesterol delivery to the mitochondrion and chronically
      increasing the transcription of steroidogenic genes (including CYP17) via a cAMP
      dependent pathway. In the present study, we characterized the role of
      sphingolipids in ACTH-dependent steroidogenesis. H295R human adrenocortical cells
      were treated with ACTH or dibutyryl cAMP (Bt2cAMP) and the content of several
      sphingolipid species quantified by mass spectrometry. Both ACTH and Bt2cAMP
      decreased cellular amounts of several sphingolipids, including sphingomyelin,
      ceramides, and sphingosine and stimulating the activity of sphingosine kinase and
      increasing the release of sphingosine-1-phosphate (S1P) into the media. S1P
      increased CYP17 mRNA expression by promoting the cleavage and nuclear
      localization of sterol regulatory element binding protein (SREBP) 1. Chromatin
      immunoprecipitation assays revealed that Bt2cAMP and S1P increased acetylation of
      histone H3 and promoted binding of SREBP1 to the -520/-331 region of the CYP17
      promoter. In summary, our studies demonstrate a role for sphingolipid metabolism
      and SREBP1 in ACTH-dependent CYP17 regulation and steroidogenesis.

PMID- 16306079
TI  - Molecular phenotyping of human endometrium distinguishes menstrual cycle phases
      and underlying biological processes in normo-ovulatory women.
AB  - Histological evaluation of endometrium has been the gold standard for clinical
      diagnosis and management of women with endometrial disorders. However, several
      recent studies have questioned the accuracy and utility of such evaluation,
      mainly because of significant intra- and interobserver variations in histological
      interpretation. To examine the possibility that biochemical or molecular
      signatures of endometrium may prove to be more useful, we have investigated whole
      genome molecular phenotyping (54,600 genes and expressed sequence tags) of this
      tissue sampled across the cycle in 28 normo-ovulatory women, using high-density
      oligonucleotide microarrays. Unsupervised principal component analysis of all
      samples revealed that samples self-cluster into four groups consistent with
      histological phenotypes of proliferative (PE), early-secretory (ESE), mid
      secretory (MSE), and late-secretory (LSE) endometrium. Independent hierarchical
      clustering analysis revealed equivalent results, with two major dendrogram
      branches corresponding to PE/ESE and MSE/LSE and sub-branching into the four
      respective phases with heterogeneity among samples within each sub-branch. K
      means clustering of genes revealed four major patterns of gene expression (high
      in PE, high in ESE, high in MSE, and high in LSE), and gene ontology analysis of
      these clusters demonstrated cycle-phase-specific biological processes and
      molecular functions. Six samples with ambiguous histology were identically
      assignable to a cycle phase by both principal component analysis and hierarchical
      clustering. Additionally, pairwise comparisons of relative gene expression across
      the cycle revealed genes/families that clearly distinguish the transitions of PE-
      >ESE, ESE-->MSE, and MSE-->LSE, including receptomes and signaling pathways.
      Select genes were validated by quantitative RT-PCR. Overall, the results
      demonstrate that endometrial samples obtained by two different sampling
      techniques (biopsy and curetting hysterectomy specimens) from subjects who are as
      normal as possible in a human study and including those with unknown histology,
      can be classified by their molecular signatures and correspond to known phases of
      the menstrual cycle with identical results using two independent analytical
      methods. Also, the results enable global identification of biological processes
      and molecular mechanisms that occur dynamically in the endometrium in the
      changing steroid hormone milieu across the menstrual cycle in normo-ovulatory
      women. The results underscore the potential of gene expression profiling for
      developing molecular diagnostics of endometrial normalcy and abnormalities and
      identifying molecular targets for therapeutic purposes in endometrial disorders.

PMID- 16306080
TI  - Estrogen induction of the granzyme B inhibitor, proteinase inhibitor 9, protects
      cells against apoptosis mediated by cytotoxic T lymphocytes and natural killer
      cells.
AB  - Exposure to estrogens is associated with an increased risk of developing breast,
      cervical, and liver cancer. Estrogens strongly induce the human granzyme B
      inhibitor, proteinase inhibitor 9 (PI-9). Because cytotoxic T lymphocytes (CTLs)
      and natural killer (NK) cells use the granzyme pathway to induce apoptosis of
      target cells, we tested the ability of activated CTLs and the human NK cell line,
      YT cells, to lyse human liver cells. Estrogen induction of PI-9 protected the
      liver cells against CTL and NK cell-mediated, granzyme-dependent, apoptosis.
      Knockdown of PI-9 by RNA interference blocked the protective effect of estrogen.
      This work demonstrates that estrogens can act on target cells to control their
      destruction by immune system cells and shows that induction of PI-9 expression
      can inhibit both CTL and NK cell-mediated apoptosis. Estrogen induction of PI-9
      may reduce the ability of cytolytic lymphocytes-mediated immune surveillance to
      destroy newly transformed cells, possibly providing a novel mechanism for an
      estrogen-mediated increase in tumor incidence.

PMID- 16306081
TI  - Activity-dependent potentiation of large dense-core vesicle release modulated by
      mitogen-activated protein kinase/extracellularly regulated kinase signaling.
AB  - Large dense-core vesicles (LDCVs), containing neuropeptides, hormones, and
      amines, play a crucial role in the activation of the sympathetic nervous system
      and synaptic modulation. In some secretory cells, LDCVs show activity-dependent
      potentiation (ADP), which represents enhancement of subsequent exocytosis,
      compared with the previous one. Here we report the signaling mechanism involved
      in ADP of LDCV release. First, ADP of LDCV release, induced by repetitive
      stimulation of nicotinic acetylcholine receptors (nAChRs), was augmented by
      increasing calcium influx, showing calcium dependence of ADP. Second,
      translocation of vesicles was involved in ADP. Electron microscope analysis
      revealed that nAChR stimulation resulted in LDCV translocation to the plasma
      membrane and increase of fused LDCVs in response to repetitive stimulation was
      observed by amperometry. Third, we provide evidence for involvement of MAPK
      signaling in ADP. MAPK signaling was activated by nAChR-induced calcium influx,
      and ADP as well as vesicle translocation was suppressed by inhibition of MAPK
      signaling with MAPK kinase blockers, such as PD 098059 and U0126. Fourth, PD
      098059 inhibited nAChR stimulation-induced F-actin disassembly, which has been
      reported to control vesicle translocation. Taken together, we suggest that ADP of
      LDCV release is modulated by calcium-dependent activation of MAPK signaling via
      regulating F-actin disassembly.

PMID- 16306082
TI  - Testicular edema is associated with spermatogonial arrest in irradiated rats.
AB  - Irradiation of LBNF1 rat testes induces arrest of spermatogonial differentiation,
      which can be reversed by suppression of testosterone with GnRH antagonist
      treatment. The cause of the arrest is unknown. We investigated the time course
      and hormonal effects on radiation-induced arrest and changes in interstitial
      fluid volume. We postulated that the edema evident in irradiated testes caused
      the differentiation blockade. Rat testes were irradiated with 3.5 or 6 Gy.
      Interstitial fluid testosterone (IFT) increased between 2 and 6 wk after
      irradiation, followed by increased interstitial fluid volume at 6 wk and
      spermatogonial blockade at 8 wk. Additional rats irradiated with 6 Gy were given
      GnRH antagonist, alone or with exogenous testosterone, for 8 wk starting at 15 wk
      after irradiation. In rats treated with GnRH antagonist, IFT started falling
      within 1 wk of treatment, followed by interstitial fluid volume decreases at wk 2
      and 3, with recovery of spermatogenesis starting at wk 4. Addition of exogenous
      testosterone largely blocked the effects of GnRH antagonist on IFT, interstitial
      fluid volume, and spermatogenesis. Thus the testicular edema was largely
      modulated by intratesticular testosterone levels. The time course of changes in
      the spermatogonial blockade more closely followed that of the testicular edema
      than of IFT, indicating that testosterone may block spermatogonial
      differentiation indirectly by producing edema. This conclusion was further
      supported by an experiment in which irradiated rats were treated with GnRH
      antagonist plus estrogen; the treatment further reduced IFT and interstitial
      fluid volume and reduced the time to initiation of recovery of spermatogonial
      differentiation. These results suggest that studies of the edematous process or
      composition of the fluid would help elucidate the mechanism of spermatogonial
      arrest in toxicant-treated rats.

PMID- 16306083
TI  - Neutrophils and macrophages promote angiogenesis in the early stage of
      endometriosis in a mouse model.
AB  - Substantial evidence suggests that inflammatory cytokines, immune cells, and
      angiogenesis are important for endometriosis. In this study, we investigated the
      role of the sequential events in the development of endometriosis in a mouse
      model. Uterine tissue was transplanted into the peritoneum of ovariectomized mice
      and then supplemented with estrogen or vehicle. On different days after
      transplantation, cell proliferation, angiogenesis, and infiltrated immune cells
      in ectopic tissue were examined using immunochemical staining. Many disintegrated
      blood vessels but no bromodeoxyuridine-positive cells in ectopic tissue were
      observed in the estrogen-treated group on posttransplantation d 1 and 2. On d 4
      7, bromodeoxyuridine-positive cells were detected in the blood vessels of ectopic
      tissue, indicating that angiogenesis was initiated in this stage. Angiogenesis
      also occurred in ectopic tissue in the vehicle-treated group. Profound
      infiltration of neutrophils in ectopic tissue occurred on d 1-4, when the number
      of neutrophils and levels of macrophage inflammatory protein (MIP)-1alpha and MIP
      2 chemokines in peritoneal fluids also reached their peak. Peritoneal macrophage
      numbers did not change, but secretions of TNFalpha, IL-6, MIP-1alpha, and MIP-2
      from macrophages isolated on d 2 were higher than on d 0. In vitro studies showed
      that peritoneal neutrophils and macrophages secreted vascular endothelial growth
      factor, which was up-regulated by TNFalpha and IL-6. Our results suggest that
      neutrophils and macrophages may promote angiogenesis in the early stage of
      endometriosis and that chemokines and cytokines amplify the angiogenic signal for
      the growth of endometriotic tissue.

PMID- 16306084
TI  - Effects of rexinoids on thyrotrope function and the hypothalamic-pituitary
      thyroid axis.
AB  - Retinoid X receptor (RXR)-selective retinoids (rexinoids) can cause central
      hypothyroidism in humans, and this effect has been confirmed in rodent models. In
      this report, we characterized the effect of rexinoids on the hypothalamic
      pituitary-thyroid axis in mice and TSH regulation in a thyrotrope-derived cell
      line. The synthetic rexinoid (LG 268) suppressed TSH and T4 levels in mice.
      Hypothalamic TRH mRNA was unaffected, but steady-state pituitary TSHbeta mRNA
      levels were significantly lowered, suggesting a direct effect of rexinoids on
      thyrotropes. LG 268 suppressed TSH protein secretion and TSHbeta mRNA in TalphaT1
      thyrotropes as early as 8 h after treatment, whereas the retinoic acid receptor
      selective retinoid (TTNPB) had no effect. Type 2 iodothyronine deiodinase (D2)
      mRNA and activity were suppressed by LG 268 in TalphaT1 cells, whereas only D2
      mRNA was suppressed in mouse pituitaries. LG 268 suppressed TSHbeta promoter
      activity by 42% and the -200 to -149 region accounted for a majority of the LG
      268-mediated suppression of promoter activity. The RXRgamma isotype is expressed
      in thyrotropes. In vitro transfection and in vivo transgenic studies indicate
      that any RXR isotype can mediate TSH suppression by rexinoids, but the RXRgamma
      isotype is most efficient at mediating this response. RXRgamma-deficient mice
      lacked pituitary D2 mRNA suppression by LG 268, but D2 activity remained intact.
      In summary, RXR-selective retinoids (rexinoids) have multiple effects on the
      hypothalamic-pituitary-thyroid axis. Rexinoids directly suppress TSH secretion,
      TSHbeta mRNA levels and promoter activity, and D2 mRNA levels but have no direct
      effect on hypothalamic TRH levels. Rexinoids also stimulate type 1 iodothyronine
      deiodinase activity in the liver and pituitary.

PMID- 16306085
TI  - Transgenic mice expressing p450 aromatase as a model for male infertility
      associated with chronic inflammation in the testis.
AB  - Our previous studies have shown that transgenic male mice expressing human P450
      aromatase (AROM+) are infertile. In the present study, we followed the testis
      phenotype up to 15 months of age in these mice. The testes of the old AROM+ mice
      showed Leydig cell hypertrophy and hyperplasia, as indicated by the staining for
      steroidogenic enzymes and androgen and estrogen receptors. However, the Leydig
      cell adenomas did not show signs of malignization. In contrast, we observed a
      marked increase in the number of activated macrophages in the testicular
      interstitium of the aging AROM+ mice. The macrophages were further shown to
      express high levels of CD68 (a monocyte/macrophage marker) and secrete TNFalpha,
      indicating strong activation, presumably by estrogen exposure. The increased
      activity of the macrophages was associated with Leydig cell depletion (analyzed
      at the age of 9 and 15 months) and an increased number of mast cells and fibrosis
      in the testicular interstitium. Interestingly, similar findings have been made in
      testes of infertile men. Hence, the aging AROM+ males present with a phenocopy of
      inflammation-associated infertility in men, providing a model for further studies
      on the putative link among estrogens, orchitis, and infertility.

PMID- 16306086
TI  - Estrogen dendrimer conjugates that preferentially activate extranuclear,
      nongenomic versus genomic pathways of estrogen action.
AB  - Estrogenic hormones are classically thought to exert their effects by binding to
      nuclear estrogen receptors and altering target gene transcription, but estrogens
      can also have nongenomic effects through rapid activation of membrane-initiated
      kinase cascades. The development of ligands that selectively activate only the
      nongenomic pathways would provide useful tools to investigate the significance of
      these pathways. We have prepared large, abiotic, nondegradable poly(amido)amine
      dendrimer macromolecules that are conjugated to multiple estrogen molecules
      through chemically robust linkages. Because of their charge and size, these
      estrogen-dendrimer conjugates (EDCs) remain outside the nucleus. They stimulate
      ERK, Shc, and Src phosphorylation in MCF-7 breast cancer cells at low
      concentrations, yet they are very ineffective in stimulating transcription of
      endogenous estrogen target genes, being approximately 10,000-fold less potent
      than estradiol in genomic actions. In contrast to estradiol, EDC was not
      effective in stimulating breast cancer cell proliferation. Because these EDC
      ligands activate nongenomic activity at concentrations at which they do not alter
      the transcription of estrogen target genes, they should be useful in studying
      extranuclear initiated pathways of estrogen action in a variety of target cells.

PMID- 16306088
TI  - Feasibility study of new calibrators for thyroid-stimulating hormone (TSH)
      immunoprocedures based on remodeling of recombinant TSH to mimic glycoforms
      circulating in patients with thyroid disorders.
AB  - BACKGROUND: Differences between the glycosylation patterns of a pituitary thyroid
      stimulating hormone calibrator (pitTSH) and serum samples have been shown to be
      responsible for nonidentical epitope expression and for introducing discrepancies
      in TSH measurements. We studied the feasibility of developing new candidate
      reference materials by remodeling recombinant TSH (recTSH) to generate potential
      mimics of serum TSH. METHODS: Terminal sialylation and/or inner fucosylation of
      recTSH were remodeled by a combination of enzyme treatments followed (or not) by
      lentil lectin-Sepharose affinity chromatography. The resulting TSH preparations
      were screened for epitope similarity in 23 immunoassays mapping 3 antigenic
      clusters common to the pitTSH 2nd International Reference Preparation (IRP) and
      the recTSH 1st IRP and then challenged against a pool of 63 patients with
      increased serum TSH (>60 mIU/L). RESULTS: pitTSH was poorly correlated with serum
      TSH, with a mean (SD) slope of 2.124 (0.001), in contrast to recTSH [slope, 1.178
      (0.056)]. Comparison of variably sialylated preparations with recTSH gave slopes
      of 0.860 (0.057) for desialylated TSH, 1.064 (0.057) for alpha2,3/6
      oversialylated recTSH, and 0.953 (0.033) for alpha2,6-resialylated recTSH,
      indicating that TSH forms enriched in sialic acid closely resemble serum TSH.
      Further testing against serum TSH showed satisfactory agreement with both TSH
      preparations containing alpha2,6-sialic acid [slopes, 1.064 (0.057) and 0.953
      (0.033)], particularly in the absence of nonfucosylated forms [0.985 (0.044)].
      CONCLUSIONS: Glyco-engineered recTSH preparations enriched in sialic acid and
      inner fucose are promising candidates for future reference materials. These
      preparations may have advantages over existing preparations used for
      standardizing TSH measurements.

PMID- 16306087
TI  - Antagonistic functions of tetradecanoyl phorbol acetate-inducible-sequence 11b
      and HuR in the hormonal regulation of vascular endothelial growth factor
      messenger ribonucleic acid stability by adrenocorticotropin.
AB  - Expression of vascular endothelial growth factor (VEGF), an endothelial cell
      specific mitogen and a potent angiogenic factor, is up-regulated by a variety of
      factors including hypoxia, growth factors, and hormones. In the adrenal cortex,
      regulation of VEGF expression by the pituitary hormone ACTH ensures the
      maintenance of the organ vasculature. We have previously shown that ACTH evokes a
      rapid and transient increase in VEGF mRNA levels in primary adrenocortical cells
      through transcription-independent mechanisms. We further demonstrated that the
      zinc finger RNA-binding protein Tis11b (tetradecanoyl phorbol acetate-inducible
      sequence 11b) destabilizes VEGF mRNA through its 3'-untranslated region (3'-UTR)
      and that Tis11b is involved in the decay phase of ACTH-induced VEGF mRNA
      expression. In the present study, we attempted to determine the mechanisms
      underlying ACTH-elicited increase in VEGF mRNA levels in adrenocortical cells. We
      show that ACTH triggers an increase in the levels of the mRNA-stabilizing protein
      HuR in the cytoplasm and a concomitant decrease in the levels of HuR in the
      nucleus. This process is accompanied by an increased association of HuR with the
      nucleocytoplasmic shuttling protein pp32, indicating that ACTH induces HuR
      translocation from the nuclear to the cytoplasmic compartment. Leptomycin B, a
      specific inhibitor of CRM1-dependent nuclear export of pp32, significantly
      reduced ACTH-induced VEGF mRNA levels. Furthermore, RNA interference-mediated
      depletion of HuR in adrenocortical cells abrogated ACTH-induced VEGF mRNA
      expression. Finally, we show that Tis11b and HuR exert antagonistic effects on
      VEGF 3'-UTR in vitro. Although both proteins could bind simultaneously on VEGF 3'
      UTR, Tis11b markedly decreases HuR-binding to this RNA sequence. Altogether,
      these results suggest that the RNA-stabilizing protein HuR is instrumental to
      ACTH-induced expression of VEGF mRNA and that the nuclear export of HuR is a rate
      limiting step in this process. HuR appears to transiently stabilize VEGF
      transcripts after ACTH stimulation of adrenocortical cells, and Tis11b appears to
      subsequently trigger their degradation.

PMID- 16306089
TI  - Western blotting of total lysate of Helicobacter pylori in cases of atrophic body
      gastritis.
AB  - BACKGROUND: Atrophic body gastritis is considered the first important step in the
      histogenesis of gastric carcinoma, a multistep process starting from chronic
      gastritis and progressing through chronic atrophic gastritis, intestinal
      metaplasia, and dysplasia. Helicobacter pylori is involved in the induction of
      atrophic body gastritis, but documentation of H. pylori infection is difficult
      because of the progressive disappearance of the bacterium. Our study aimed to
      detect past H. pylori infection in patients with atrophic body gastritis.
      METHODS: We used Western blot analyses of whole bacterial protein lysate of 2
      different strains to probe sera from 143 patients. All sera were analyzed by
      ELISA (Bio-Rad), and results of gastric histology were available for all
      patients. RESULTS: Among 111 patient sera previously classified as negative for
      H. pylori infection by ELISA, 106 (95.5%) were positive when assayed by
      immunoblotting. CONCLUSIONS: Commercial diagnostic reagent sets may fail to
      detect H. pylori infection. Western blotting of whole bacterial protein extracts
      could provide the basis of a noninvasive serology tool able to assess previous
      infection with H. pylori in patients with atrophic body gastritis.

PMID- 16306090
TI  - Characterization of a new certified reference material for human cardiac troponin
      I.
AB  - BACKGROUND: To address the continuing need for the standardization of clinical
      human cardiac troponin I (cTnI) assays, NIST, with the assistance of the
      AACC/IFCC Cardiac Troponin I Standardization Committee, has developed a new
      certified reference material, Standard Reference Material (SRM) 2921: Human
      Cardiac Troponin Complex. METHODS: The concentration of cTnI in SRM 2921 was
      determined through a combination of reversed-phase liquid chromatography (LC)
      with ultraviolet detection and amino acid analysis. Characterization of the
      intact troponin subunits was accomplished through reversed-phase LC coupled with
      mass spectrometry. Posttranslational modifications to the cTnI in SRM 2921 were
      investigated by combining proteolytic digestion with matrix-assisted laser
      desorption/ionization mass spectrometry. Additionally, reference concentration
      values for cTnT and cTnC were also determined. RESULTS: The concentration of
      human cTnI in SRM 2921 is 31.2 (1.4) mg/L (where 1.4 mg/L is the uncertainty at a
      95% level of confidence), as certified through a method that provides
      traceability to the International System of Units (SI). Reference concentration
      values of the cTnT and cTnC subunits were determined to be 36.9 (3.8) mg/L and
      24.2 (1.3) mg/L, respectively. CONCLUSIONS: This first cTnI reference material
      should provide SI traceability to clinical cTnI assays once commutability has
      been validated, and could assist in the international harmonization of cTnI
      assays as a tool for understanding the underlying causes of interassay
      variability.

PMID- 16306091
TI  - Perspective on the historical note on EIA/ELISA by Dr. R.M. Lequin.

PMID- 16306092
TI  - The rise of EIA/ELISA.

PMID- 16306093
TI  - Monitoring osteoporosis therapy.

PMID- 16306094
TI  - Amplification of nanogram amounts of total RNA by the SMART-based PCR method for
      high-density oligonucleotide microarrays.

PMID- 16306095
TI  - Identification of novel mutations in patients with Coffin-Lowry syndrome by a
      denaturing HPLC-based assay.

PMID- 16306096
TI  - Detection of trisomy 21 by quantitative mass spectrometric analysis of single
      nucleotide polymorphisms.

PMID- 16306097
TI  - Urinary osteocalcin is a useful marker for monitoring the effect of alendronate
      therapy.

PMID- 16306098
TI  - Effect of specimen anticoagulation on the measurement of circulating platelet
      derived growth factors.

PMID- 16306099
TI  - Analysis of carbohydrate-deficient transferrin: comparative evaluation of
      turbidimetric immunoassay, capillary zone electrophoresis, and HPLC.

PMID- 16306100
TI  - Genetic variation in the MTHFR gene influences thiopurine methyltransferase
      activity.

PMID- 16306101
TI  - Prepercutaneous coronary intervention plasma homocysteine concentration is a
      useful predictor of angioplasty-induced myocardial damage.

PMID- 16306102
TI  - Sensitive spectrophotometric assay for plasma oxalate.

PMID- 16306103
TI  - Determination of coenzyme Q10 status in blood mononuclear cells, skeletal muscle,
      and plasma by HPLC with di-propoxy-coenzyme Q10 as an internal standard.

PMID- 16306104
TI  - Serum tartrate-resistant acid phosphatase 5b or amino-terminal propeptide of type
      I procollagen for monitoring bisphosphonate therapy in postmenopausal
      osteoporosis?

PMID- 16306105
TI  - Variation with time in components of variance for measurements of therapeutic
      drugs.

PMID- 16306106
TI  - Detection of MC1R polymorphisms with protease-mediated allele-specific extension
      as an alternative to direct sequencing.

PMID- 16306107
TI  - Toward the development of a lab-on-a-chip dual-function leukocyte and C-reactive
      protein analysis method for the assessment of inflammation and cardiac risk.

PMID- 16306108
TI  - Quantitative assessment of human beta-globin gene expression in vitro by TaqMan
      real-time reverse transcription-PCR: comparison with competitive reverse
      transcription-PCR and application to mutations or deletions in noncoding regions.

PMID- 16306109
TI  - Light-shielded hemodialysis prevents hypotension and lipid peroxidation by
      inhibiting nitric oxide production.

PMID- 16306110
TI  - Investigation of the genomic representation of plasma DNA in pregnant women by
      comparative genomic hybridization analysis: a feasibility study.

PMID- 16306111
TI  - Blood catalase activity in gestational diabetes is decreased but not associated
      with pregnancy complications.

PMID- 16306112
TI  - Addition of a homologous internal control to a real-time PCR assay for detection
      of Bordetella pertussis.

PMID- 16306113
TI  - Process improvement and operational efficiency through test result
      autoverification.

PMID- 16306114
TI  - Preanalytical impact of sample handling on proteome profiling experiments with
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

PMID- 16306115
TI  - SDF1-3'A gene polymorphism is associated with chronic myeloproliferative disease
      and thrombotic events.

PMID- 16306116
TI  - Use of an automated method improves the yield and quality of cell-free fetal DNA
      extracted from maternal plasma.

PMID- 16306117
TI  - Unambiguous identification of the expressed MAGE-A genes on a DNA microarray.

PMID- 16306118
TI  - Processing controls in blood collection tubes reveals interference.

PMID- 16306119
TI  - Tissue differences in the expression of mutations and polymorphisms in the GRHPR
      gene and implications for diagnosis of primary hyperoxaluria type 2.

PMID- 16306120
TI  - Increased lipid concentration is associated with increased hemolysis.

PMID- 16306121
TI  - Antibodies to extractable nuclear antigens in antinuclear antibody-negative
      samples.

PMID- 16306123
TI  - Involvement of calmodulin and myosin light chain kinase in activation of mTRPC5
      expressed in HEK cells.
AB  - The classic type of transient receptor potential channel (TRPC) is a molecular
      candidate for Ca(2+)-permeable cation channels in mammalian cells. Because TRPC
      channels have calmodulin (CaM) binding sites at their COOH termini, we
      investigated the effect of CaM on mTRPC5. TRPC5 was initially activated by
      muscarinic stimulation with 50 microM carbachol and then decayed rapidly even in
      the presence of carbachol. Intracellular CaM (150 microg/ml) increased the
      amplitude of mTRPC5 current activated by muscarinic stimulation. CaM antagonists
      (W-7 and calmidazolium) inhibited mTRPC5 currents when they were applied during
      the activation of mTRPC5. Pretreatment of W-7 and calmidazolium also inhibited
      the activation of mTRPC5 current. Inhibitors of myosin light chain kinase (MLCK)
      inhibited the activation of mTRPC5 currents, whereas inhibitors of CaM-dependent
      protein kinase II did not. Small interfering RNA against cardiac type MLCK also
      inhibited the activation of mTRPC5 currents. However, inhibitors of CaM or MLCK
      did not show any effect on GTPgammaS-induced currents. Application of both Rho
      kinase inhibitor and MLCK inhibitor inhibited GTPgammaS-induced currents. We
      conclude that CaM and MLCK modulates the activation process of mTRPC5.

PMID- 16306124
TI  - Intermittent hypoxia protects cardiomyocytes against ischemia-reperfusion injury
      induced alterations in Ca2+ homeostasis and contraction via the sarcoplasmic
      reticulum and Na+/Ca2+ exchange mechanisms.
AB  - We have previously demonstrated that intermittent high-altitude (IHA) hypoxia
      significantly attenuates ischemia-reperfusion (I/R) injury-induced excessive
      increase in resting intracellular Ca(2+) concentrations ([Ca(2+)](i)). Because
      the sarcoplasmic reticulum (SR) and Na(+)/Ca(2+) exchanger (NCX) play crucial
      roles in regulating [Ca(2+)](i) and both are dysfunctional during I/R, we tested
      the hypothesis that IHA hypoxia may prevent I/R-induced Ca(2+) overload by
      maintaining Ca(2+) homeostasis via SR and NCX mechanisms. We thus determined the
      dynamics of Ca(2+) transients and cell shortening during preischemia and I/R
      injury in ventricular cardiomyocytes from normoxic and IHA hypoxic rats. IHA
      hypoxia did not affect the preischemic dynamics of Ca(2+) transients and cell
      shortening, but it significantly suppressed the I/R-induced increase in resting
      [Ca(2+)](i) levels and attenuated the depression of the Ca(2+) transients and
      cell shortening during reperfusion. Moreover, IHA hypoxia significantly
      attenuated I/R-induced depression of the protein contents of SR Ca(2+) release
      channels and/or ryanodine receptors (RyRs) and SR Ca(2+) pump ATPase (SERCA2) and
      SR Ca(2+) release and uptake. In addition, a delayed decay rate time constant of
      Ca(2+) transients and cell shortening of Ca(2+) transients observed during
      ischemia was accompanied by markedly inhibited NCX currents, which were prevented
      by IHA hypoxia. These findings indicate that IHA hypoxia may preserve Ca(2+)
      homeostasis and contraction by preserving RyRs and SERCA2 proteins as well as NCX
      activity during I/R.

PMID- 16306125
TI  - Long-lasting muscle fatigue: partial disruption of excitation-contraction
      coupling by elevated cytosolic Ca2+ concentration during contractions.
AB  - The repeated elevation of cytosolic Ca(2+) concentration ([Ca(2+)](i)) above
      resting levels during contractile activity has been associated with long-lasting
      muscle fatigue. The mechanism underlying this fatigue appears to involve elevated
      [Ca(2+)](i) levels that induce disruption of the excitation-contraction (E-C)
      coupling process at the triad junction. Unclear, however, are which aspects of
      the activity-related [Ca(2+)](i) changes are responsible for the deleterious
      effects, in particular whether they depend primarily on the peak [Ca(2+)](i)
      reached locally at particular sites or on the temporal summation of the increased
      [Ca(2+)] in the cytoplasm as a whole. In this study, we used mechanically skinned
      fibers from rat extensor digitorum longus muscle, in which the normal E-C
      coupling process remains intact. The [Ca(2+)](i) was raised either by applying a
      set elevated [Ca(2+)] throughout the fiber or by using action potential
      stimulation to induce the release of sarcoplasmic reticulum Ca(2+) by the normal
      E-C coupling system with or without augmentation by caffeine or buffering with
      BAPTA. Herein we show that elevating [Ca(2+)](i) in the physiological range of 2
      20 microM irreversibly disrupts E-C coupling in a concentration-dependent manner
      but requires exposure for a relatively long time (1-3 min) to cause substantial
      uncoupling. The effectiveness of Ca(2+) released via the endogenous system in
      disrupting E-C coupling indicates that the relatively high [Ca(2+)](i) attained
      close to the release site at the triad junction is a more important factor than
      the increase in bulk [Ca(2+)](i). Our results suggest that during prolonged
      vigorous activity, the many repeated episodes of relatively high triadic [Ca(2+)]
      can disrupt E-C coupling and lead to long-lasting fatigue.

PMID- 16306126
TI  - Altered gating and regulation of a carboxy-terminal ClC channel mutant expressed
      in the Caenorhabditis elegans oocyte.
AB  - CLH-3a and CLH-3b are swelling-activated, alternatively spliced Caenorhabditis
      elegans ClC anion channels that have identical membrane domains but exhibit
      marked differences in their cytoplasmic NH(2) and COOH termini. The major
      differences include a 71-amino acid CLH-3a NH(2)-terminal extension and a 270
      amino acid extension of the CLH-3b COOH terminus. Splice variation gives rise to
      channels with striking differences in voltage, pH, and Cl(-) sensitivity. On the
      basis of structural and functional insights gained from crystal structures of
      bacterial ClCs, we suggested previously that these functional differences are due
      to alternative splicing of the COOH terminus that may change the accessibility
      and/or function of pore-associated ion-binding sites. We recently identified a
      mutant worm strain harboring a COOH-terminal deletion mutation in the clh-3 gene.
      This mutation removes 101 COOH-terminal amino acids unique to CLH-3b and an
      additional 64 upstream amino acids shared by both channels. CLH-3b is expressed
      in the worm oocyte, which allowed us to characterize the mutant channel, CLH
      3bDeltaC, in its native cellular environment. CLH-3bDeltaC exhibits altered
      voltage-dependent gating as well as pH and Cl(-) sensitivity that resemble those
      of CLH-3a. This mutation also alters channel inhibition by Zn(2+), prevents ATP
      depletion-induced activation, and dramatically reduces volume sensitivity. These
      results suggest that the deleted COOH-terminal region of CLH-3bDeltaC functions
      to modulate channel sensitivity to voltage and extracellular ions. This region
      also likely plays a role in channel regulation and cell volume sensitivity. Our
      findings contribute to a growing body of evidence indicating that cytoplasmic
      domains play key roles in the gating and regulation of eukaryotic ClCs.

PMID- 16306127
TI  - Defective thyroglobulin storage in LDL receptor-associated protein-deficient
      mice.
AB  - The molecular chaperone receptor-associated protein (RAP) is required for
      biosynthesis of megalin, an endocytic receptor for follicular thyroglobulin (Tg),
      the thyroid hormone precursor. RAP also binds to Tg itself, suggesting that it
      may affect Tg trafficking in various manners. To elucidate RAP function, we have
      studied the thyroid phenotype in RAP-knockout (RAP-KO) mice and found a reduction
      of Tg aggregates into thyroid follicles. Serum Tg levels were significantly
      increased compared with those of wild-type (WT) mice, suggesting a directional
      alteration of Tg secretion. In spite of these abnormalities, hormone secretion
      was maintained as indicated by normal serum thyroxine levels. Because Tg in
      thyroid extracts from RAP-KO mice contained thyroxine residues as in WT mice, we
      concluded that in RAP-KO mice, follicular Tg, although reduced, was nevertheless
      sufficient to provide normal hormone secretion. Serum TSH was increased in RAP-KO
      mice, and although no thyroid enlargement was observed, some histological
      features resembling early goiter were present. Megalin was decreased in RAP-KO
      mice, but this did not affect thyroid function, probably because of the
      concomitant reduction of follicular Tg. In conclusion, RAP is required for the
      establishment of Tg reservoirs, but its absence does not affect hormone
      secretion.

PMID- 16306128
TI  - Dominant-negative effects of human P/Q-type Ca2+ channel mutations associated
      with episodic ataxia type 2.
AB  - Episodic ataxia type 2 (EA2) is an inherited autosomal dominant disorder related
      to cerebellar dysfunction and is associated with mutations in the pore-forming
      alpha(1A)-subunits of human P/Q-type Ca(2+) channels (Cav2.1 channels). The
      majority of EA2 mutations result in significant loss-of-function phenotypes.
      Whether EA2 mutants may display dominant-negative effects in human, however,
      remains controversial. To address this issue, five EA2 mutants in the long
      isoform of human alpha(1A)-subunits were expressed in Xenopus oocytes to explore
      their potential dominant-negative effects. Upon coexpressing the cRNA of
      alpha(1A)-WT with each alpha(1A)-mutant in molar ratios ranging from 1:1 to 1:10,
      the amplitude of Ba(2+) currents through wild-type (WT)-Cav2.1 channels decreased
      significantly as the relative molar ratio of alpha(1A)-mutants increased,
      suggesting the presence of an alpha(1A)-mutant-specific suppression effect. When
      we coexpressed alpha(1A)-WT with proteins not known to interact with Cav2.1
      channels, we observed no significant suppression effects. Furthermore, increasing
      the amount of auxiliary subunits resulted in partial reversal of the suppression
      effects in nonsense but not missense EA2 mutants. On the other hand, when we
      repeated the same coinjection experiments of alpha(1A)-WT and mutant using a
      splice variant of alpha(1A)-subunit that contained a considerably shorter COOH
      terminus (i.e., the short isoform), no significant dominant-negative effects were
      noted until we enhanced the relative molar ratio to 1:10. Altogether, these
      results indicate that for human WT-Cav2.1 channels comprising the long-alpha(1A)
      subunit isoform, both missense and nonsense EA2 mutants indeed display prominent
      dominant-negative effects.

PMID- 16306129
TI  - TRPM2 is an ion channel that modulates hematopoietic cell death through
      activation of caspases and PARP cleavage.
AB  - TRPM2 is a Ca(2+)-permeable channel activated by oxidative stress or TNF-alpha,
      and TRPM2 activation confers susceptibility to cell death. The mechanisms were
      examined here in human monocytic U937-ecoR cells. This cell line expresses full
      length TRPM2 (TRPM2-L) and several isoforms including a short splice variant
      lacking the Ca(2+)-permeable pore region (TRPM2-S), which functions as a dominant
      negative. Treatment with H(2)O(2), a model of oxidative stress, or TNF-alpha
      results in reduced cell viability. Expression of TRPM2-L and TRPM2-S was
      modulated by retroviral infection. U937-ecoR cells expressing increased levels of
      TRPM2-L were treated with H(2)O(2) or TNF-alpha, and these cells exhibited
      significantly increased intracellular calcium concentration ([Ca(2+)](i)),
      decreased viability, and increased apoptosis. A dramatic increase in cleavage of
      caspases-8, -9, -3, and -7 and poly(ADP-ribose)polymerase (PARP) was observed,
      demonstrating a downstream mechanism through which cell death is mediated. Bcl-2
      levels were unchanged. Inhibition of the [Ca(2+)](i) rise with the intracellular
      Ca(2+) chelator BAPTA blocked caspase/PARP cleavage and cell death induced after
      activation of TRPM2-L, demonstrating the critical role of [Ca(2+)](i) in
      mediating these effects. Downregulation of endogenous TRPM2 by RNA interference
      or increased expression of TRPM2-S inhibited the rise in [Ca(2+)](i), enhanced
      cell viability, and reduced numbers of apoptotic cells after exposure to
      oxidative stress or TNF-alpha, demonstrating the physiological importance of
      TRPM2. Our data show that one mechanism through which oxidative stress or TNF
      alpha mediates cell death is activation of TRPM2, resulting in increased
      [Ca(2+)](i), followed by caspase activation and PARP cleavage. Inhibition of
      TRPM2-L function by reduction in TRPM2 levels, interaction with TRPM2-S, or
      Ca(2+) chelation antagonizes this important cell death pathway.

PMID- 16306130
TI  - Soluble factors from Lactobacillus GG activate MAPKs and induce cytoprotective
      heat shock proteins in intestinal epithelial cells.
AB  - Conditioned media from the probiotic Lactobacillus GG (LGG-CM) induce heat shock
      protein (Hsp) expression in intestinal epithelial cells. LGG-CM induces both
      Hsp25 and Hsp72 in a time- and concentration-dependent manner. These effects are
      mediated by a low-molecular-weight peptide that is acid and heat stable. DNA
      microarray experiments demonstrate that Hsp72 is one of the most highly
      upregulated genes in response to LGG-CM treatment. Real-time PCR and
      electrophoretic mobility shift assay confirm that regulation of Hsp induction is
      at least in part transcriptional in nature, involving heat shock factor-1.
      Although Hsps are not induced for hours after exposure, transient exposure to LGG
      CM is sufficient to initiate the signal for Hsp induction, suggesting that signal
      transduction pathways may be involved. Experiments confirm that LGG-CM modulates
      the activity of certain signaling pathways in intestinal epithelial cells by
      activating MAP kinases. Inhibitors of p38 and JNK block the expression of Hsp72
      normally induced by LGG-CM. Functional studies indicate that LGG-CM treatment of
      gut epithelial cells protects them from oxidant stress, perhaps by preserving
      cytoskeletal integrity. By inducing the expression of cytoprotective Hsps in gut
      epithelial cells, and by activating signal transduction pathways, the peptide
      product(s) secreted by LGG may contribute to the beneficial clinical effects
      attributed to this probiotic.

PMID- 16306131
TI  - Curcumin suppresses the expression of extracellular matrix genes in activated
      hepatic stellate cells by inhibiting gene expression of connective tissue growth
      factor.
AB  - Upon liver injury, quiescent hepatic stellate cells (HSCs), the most relevant
      cell type for hepatic fibrogenesis, become active and overproduce extracellular
      matrix (ECM). Connective tissue growth factor (CTGF) promotes ECM production.
      Overexpression of CTGF during hepatic fibrogenesis is induced by transforming
      growth factor (TGF)-beta. We recently demonstrated that curcumin reduced cell
      growth and inhibited ECM gene expression in activated HSCs. Curcumin induced gene
      expression of peroxisome proliferator-activated receptor (PPAR)-gamma and
      stimulated its activity in activated HSCs, which was required for curcumin to
      suppress ECM gene expression, including alphaI(I)-collagen. The underlying
      mechanisms remain largely unknown. The aim of this study was to elucidate the
      mechanisms by which curcumin suppresses alphaI(I)-collagen gene expression in
      activated HSCs. We hypothesize that inhibition of alphaI(I)-collagen gene
      expression in HSCs by curcumin is mediated by suppressing CTGF gene expression
      through attenuating oxidative stress and interrupting TGF-beta signaling. The
      present report demonstrated that curcumin significantly reduced the abundance of
      CTGF in passaged HSCs and suppressed its gene expression. Exogenous CTGF dose
      dependently abrogated the inhibitory effect of curcumin. Activation of PPAR-gamma
      by curcumin resulted in the interruption of TGF-beta signaling by suppressing
      gene expression of TGF-beta receptors, leading to inhibition of CTGF gene
      expression. The phytochemical showed its potent antioxidant property by
      significantly increasing the level of total glutathione (GSH) and the ratio of
      GSH to GSSG in activated HSCs. De novo synthesis of cellular GSH was a
      prerequisite for curcumin to interrupt TGF-beta signaling and inhibited gene
      expression of CTGF and alphaI(I)-collagen in activated HSCs. Taken together, our
      results demonstrate that inhibition of alphaI(I)-collagen gene expression by
      curcumin in activated HSCs results from suppression of CTGF gene expression
      through increasing cellular GSH contents and interruption of TGF-beta signaling.
      These results provide novel insights into the mechanisms underlying inhibition of
      HSC activation by curcumin.

PMID- 16306132
TI  - Opposite action of S-adenosyl methionine and its metabolites on CYP2E1-mediated
      toxicity in pyrazole-induced rat hepatocytes and HepG2 E47 cells.
AB  - S-adenosyl-L-methionine (SAMe) is protective against a variety of hepatotoxins,
      including ethanol. The ability of SAMe to protect against cytochrome P-450 2E1
      (CYP2E1)-dependent toxicity was studied in hepatocytes from pyrazole-treated rats
      and HepG2 E47 cells, both of which actively express CYP2E1. Toxicity was
      initiated by the addition of arachidonic acid (AA) or by depletion of glutathione
      after treatment with L-buthionine sulfoximine (BSO). In pyrazole hepatocytes,
      SAMe (0.25-1 mM) protected against AA but not BSO toxicity. SAMe elevated GSH
      levels, thus preventing the decline in GSH caused by AA, and SAMe prevented AA
      induced lipid peroxidation. SAMe analogs such as methionine or S-adenosyl
      homocysteine, which elevate GSH, also protected against AA toxicity. 5'
      Methylthioadenosine (MTA), which cannot produce GSH, did not protect. The
      toxicity of BSO was not prevented by SAMe and the analogs because GSH cannot be
      synthesized. In contrast, in E47 cells, SAMe and MTA but not methionine or S
      adenosyl homocysteine potentiated AA and BSO toxicity. Antioxidants such as
      trolox or N-acetyl cysteine prevented this synergistic toxicity of SAMe plus AA
      or SAMe plus BSO, respectively. In pyrazole hepatocytes, SAMe prevented the
      decline in mitochondrial membrane potential produced by AA, whereas in E47 cells,
      SAMe potentiated the decline in mitochondrial membrane potential. In E47 cells,
      but not pyrazole hepatocytes, the combination of SAMe plus BSO lowered levels of
      the antioxidant transcription factor Nrf2. Because SAMe can be metabolized
      enzymatically or spontaneously to MTA, MTA may play a role in the potentiation of
      AA and BSO toxicity by SAMe, but the exact mechanisms require further
      investigation. In conclusion, contrasting effects of SAMe on CYP2E1 toxicity were
      observed in pyrazole hepatocytes and E47 cells. In hepatocytes, SAMe protects
      against CYP2E1 toxicity by a mechanism involving maintaining or elevating GSH
      levels.

PMID- 16306133
TI  - Altered metaplastic response of waved-2 EGF receptor mutant mice to acute oxyntic
      atrophy.
AB  - Metaplastic cell lineages are putative precursors for the development of gastric
      adenocarcinoma. The loss of parietal cells (oxyntic atrophy) is the initiating
      step in the evolution of gastric fundic mucosal lineage changes including
      metaplasia and hyperplasia. However, the intrinsic mucosal factors that promote
      and modulate the emergence of metaplastic phenotypes remain obscure. Over the
      past several years, we have studied pharmacologically induced, reversible oxyntic
      atrophy in rodents treated with DMP-777, a drug that acts as a parietal cell
      secretory membrane protonophore. DMP-777 elicits a rapid loss of parietal cells
      followed by the emergence of foveolar hyperplasia and spasmolytic polypeptide
      (SP)-expressing metaplasia (SPEM). The objective of the present study was to
      provide further insights into the intrinsic mucosal factors regulating the
      emergence of SPEM in the setting of oxyntic atrophy. We therefore studied the
      effects of DMP-777 administration on both SP/trefoil factor (TFF)2-deficient
      mice, which lack SP/TFF2, a marker of SPEM, and waved-2 mice, which harbor a
      point mutation in the EGF receptor that attenuates its tyrosine kinase activity.
      As in wild-type mice, treatment with DMP-777 for 7 days did elicit SPEM in
      SP/TFF2-deficient mice. These results suggest that SP/TFF2 does not impact on the
      development of metaplasia after the induction of parietal cell loss. In contrast,
      waved-2 homozygous mice displayed accelerated SPEM development by 3 days of
      treatment with DMP-777. These findings indicate that attenuation of EGF receptor
      signaling in waved-2 mice does elicit a more rapid emergence of SPEM. The results
      support a role for EGF receptor ligands in the regulation of gastric metaplasia.

PMID- 16306134
TI  - Roles of epidermal growth factor and Na+/H+ exchanger-1 in esophageal epithelial
      defense against acid-induced injury.
AB  - Epidermal growth factor (EGF) is predominantly secreted by salivary glands and
      activates Na(+)/H(+) exchanger-1 (NHE-1), which regulates intracellular pH
      (pH(i)). We investigated the roles of EGF and NHE-1 in esophageal epithelial
      defense against acid using human esophageal epithelial cell lines and a rat
      chronic esophagitis model. Esophageal epithelial cells were incubated with
      acidified medium in the absence or presence of EGF. Cell viability and changes in
      pH(i) were measured. Chronic acid reflux esophagitis was induced in rats with and
      without sialoadenectomy. Esophageal lesion index, epithelial proliferation, and
      expression of EGF receptors and NHE-1 were examined. EGF protected esophageal
      epithelial cells against acid in a dose-dependent manner, and the cytoprotective
      effect of EGF was completely blocked by treatment with NHE-1 inhibitors. Tyrosine
      kinase, calmodulin, and PKC inhibitors significantly inhibited cytoprotection by
      EGF, whereas MEK, phosphatidylinositol 3-kinase, and PKA inhibitors had no
      effect. EGF significantly increased pH(i) recovery after NH(4)Cl pulse
      acidification, and this increase in pH(i) recovery was significantly blocked by
      inhibitors of calmodulin and PKC. Sialoadenectomy led to an increase in the
      severity of chronic esophagitis but affected neither epithelial proliferation nor
      expression of EGF receptors. Expression of NHE-1 mRNA was increased in
      esophagitis and upregulated in rats with sialoadenectomy. The increasing severity
      of esophagitis in rats with sialoadenectomy was prevented by exogenous
      administration of EGF. In conclusion, EGF protects esophageal epithelial cells
      against acid through NHE activation via Ca(2+)/calmodulin and the PKC pathway.
      Deficiency in endogenous EGF is associated with increased severity of
      esophagitis. EGF and NHE-1 play crucial roles in esophageal epithelial defense
      against acid.

PMID- 16306135
TI  - The protective effect of L-carnitine in peripheral blood human lymphocytes
      exposed to oxidative agents.
AB  - Literature data indicate L-carnitine (LC), a trans-mitochondrial carrier of
      acetyl and long chain groups, as an agent possessing protective effects against
      oxidative stress in mammalian cells. However, the major factor involved in the
      protective mechanism is not known. The protection activity exerted by this agent
      against reactive oxygen species induced by hydrogen peroxide (H2O2) and t
      butylhydroperoxide (t-butyl-OOH) treatment in isolated human peripheral blood
      lymphocytes (PBLs) has been studied. Human lymphocytes cells were isolated and
      pre-incubated with 5 mM LC before H2O2 (100 microM) and t-butyl-OOH (400 microM)
      treatment. The protective effect of LC on treated PBLs was measured by single
      cell gel electrophoresis and the analysis of chromosomal aberrations. Results
      show that lc treated cells exhibited a significant decrease in the number of
      oxidative induced single-strand breaks and chromosomal aberrations.

PMID- 16306136
TI  - IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of
      IGF1, IGFBP3 and risk of breast cancer.
AB  - Experimental and observational studies in humans and animals suggest that insulin
      like growth factor 1 (IGF1) and its principal binding protein, IGFBP3, may
      influence breast cancer susceptibility. We have examined the association of nine
      and four single nucleotide polymorphisms (SNPs) in the IGF1 gene and in the
      IGFBP3 genes, respectively, with circulating levels of their gene products in a
      population-based study of 600 middle-aged men and women, and in a breast cancer
      case-control study, comprised 4647 cases and 4564 controls. All study
      participants are from the East Anglian region of UK. SNPs were specifically
      chosen to tag all other known SNPs in each gene. Several SNPs in each gene are
      associated both with circulating levels of their respective proteins and with
      risk of breast cancer. In particular, the c allele of IGF1 SNPrs1520220 is
      associated with increased circulating IGF1 (r2=2.1%, P-trend=0.003) in females
      and an increased risk of breast cancer: odds ratio (OR) (cc/gg)=1.41; 95%
      confidence intervals (95% CI) 1.11-1.79, P-trend=0.03. The a allele of IGFBP3 SNP
      rs2854744 is associated with increased circulating IGFBP3 (r2=9.7%, P<10(-9)) and
      a decreased risk of breast cancer: OR (aa/cc)=0.87; 95% CI 0.77-0.99, P=0.03. Our
      data indicate that common variants in the IGF1 and IGFBP3 genes are associated
      with differences in circulating levels of IGF1 and IGFBP3 and with breast cancer
      risk. More specifically and consistent with experimental models, our data suggest
      that higher IGF1 levels may increase the risk of breast cancer but higher IGFBP3
      levels may be protective.

PMID- 16306137
TI  - Effect of polyethylene glycol electrolyte balanced solution on patients with
      acute colonic pseudo obstruction after resolution of colonic dilation: a
      prospective, randomised, placebo controlled trial.
AB  - BACKGROUND AND AIMS: Conservative therapy for patients with acute colonic pseudo
      obstruction (Ogilvie's syndrome) may be successful initially but relapses are
      common. The aim of the present study was to evaluate the effect of polyethylene
      glycol (PEG) electrolyte balanced solution on the relapse rate of the syndrome
      after initial resolution with neostigmine or endoscopic decompression. PATIENTS
      AND METHODS: The study was performed on 30 consecutive patients who presented
      with abdominal distension and radiographic evidence of colonic dilation, with a
      caecal diameter > or = 10 cm, that resolved conservatively. Patients then were
      randomised to receive daily 29.5 g of PEG (n = 15) or similar placebo (n = 15).
      Patients were monitored daily for a seven day period for stool and flatus
      evacuations, and colonic diameter on abdominal radiographs. Administration of the
      test solutions and assessment of patient symptoms and x rays were performed in a
      blinded fashion. A caecal diameter > or = 8 cm with a concomitant > or =10%
      increase after initial successful therapeutic intervention was considered as a
      relapse and these patients, after a second therapeutic intervention, were
      eligible to receive open label PEG. RESULTS: Twenty five patients received
      neostigmine as the initial therapeutic intervention which resulted in resolution
      of colonic dilation in 88% of cases. Eight patients had successful endoscopic
      decompression. Five (33.3%) patients in the placebo group had recurrent caecal
      dilation compared with none in the PEG group (p = 0.04). Therapy with PEG
      resulted in a significant increase in stool and flatus evacuations (p = 0.001 and
      0.032, respectively) as well as in a significant decrease in the diameter of
      caecum, ascending and transverse colon, and abdominal circumference (p = 0.017,
      0.018, 0.014, and 0.008, respectively). CONCLUSIONS: Administration of PEG in
      patients with Ogilvie's syndrome after initial resolution of colonic dilation may
      increase the sustained response rate after initial therapeutic intervention.

PMID- 16306138
TI  - Bleomycin initiates apoptosis of lung epithelial cells by ROS but not by Fas/FasL
      pathway.
AB  - Epithelial cells are considered to be a main target of bleomycin-induced lung
      injury, which leads to fibrosis in vivo. We studied the characteristics of in
      vitro bleomycin-induced apoptosis in a mouse lung epithelial (MLE) cell line.
      Bleomycin caused an increase of reactive oxygen species (ROS) resulting in
      oxidative stress, mitochondrial leakage, and apoptosis. These were associated
      with elevated caspase-8 and resultant caspase-9 activity and with upregulation of
      Fas expression. Glutathione and inhibitors of caspase-8 or caspase-9, but not of
      FasL, inhibited these effects, suggesting their dependence on ROS, caspase-8 and 
      9, in a Fas/FasL-independent pathway. However, postbleomycin-exposed MLE cells
      were more sensitive to Fas-mediated apoptosis. These results demonstrate that the
      initial bleomycin-induced oxidative stress causes a direct apoptotic effect in
      lung epithelial cells involving a regulatory role of caspase-8 on caspase-9. Fas
      represents an amplification mechanism, and not a direct trigger of bleomycin
      induced epithelial cell apoptosis.

PMID- 16306139
TI  - Role of salicylic acid and fatty acid desaturation pathways in ssi2-mediated
      signaling.
AB  - Stearoyl-acyl carrier protein desaturase-mediated conversion of stearic acid to
      oleic acid (18:1) is the key step that regulates the levels of unsaturated fatty
      acids (FAs) in cells. Our previous work with the Arabidopsis (Arabidopsis
      thaliana) ssi2/fab2 mutant and its suppressors demonstrated that a balance
      between glycerol-3-phosphate (G3P) and 18:1 levels is critical for the regulation
      of salicylic acid (SA)- and jasmonic acid-mediated defense signaling in the
      plant. In this study, we have evaluated the role of various genes that have an
      impact on SA, resistance gene-mediated, or FA desaturation (FAD) pathways on ssi2
      mediated signaling. We show that ssi2-triggered resistance is dependent on EDS1,
      PAD4, EDS5, SID2, and FAD7 FAD8 genes. However, ssi2-triggered defects in the
      jasmonic acid pathway, morphology, and cell death phenotypes are independent of
      the EDS1, EDS5, PAD4, NDR1, SID2, FAD3, FAD4, FAD5, DGD1, FAD7, and FAD7 FAD8
      genes. Furthermore, the act1-mediated rescue of ssi2 phenotypes is also
      independent of the FAD2, FAD3, FAD4, FAD5, FAD7, and DGD1 genes. Since exogenous
      application of glycerol converts wild-type plants into ssi2 mimics, we also
      studied the effect of exogenous application of glycerol on mutants impaired in
      resistance-gene signaling, SA, or fad pathways. Glycerol increased SA levels and
      induced pathogenesis-related gene expression in all but sid2, nahG, fad7, and
      fad7 fad8 plants. Furthermore, glycerol-induced phenotypes in various mutant
      lines correlate with a concomitant reduction in 18:1 levels. Inability to convert
      glycerol into G3P due to a mutation in the nho1-encoded glycerol kinase renders
      plants tolerant to glycerol and unable to induce the SA-dependent pathway. A
      reduction in the NHO1-derived G3P pool also results in a partial age-dependent
      rescue of the ssi2 morphological and cell death phenotypes in the ssi2 nho1
      plants. The glycerol-mediated induction of defense was not associated with any
      major changes in the lipid profile and/or levels of phosphatidic acid. Taken
      together, our results suggest that glycerol application and the ssi2 mutation in
      various mutant backgrounds produce similar effects and that restoration of ssi2
      phenotypes is not associated with the further desaturation of 18:1 to linoleic or
      linolenic acids in plastidal or extraplastidal lipids.

PMID- 16306140
TI  - Metabolite profiling of Chlamydomonas reinhardtii under nutrient deprivation.
AB  - A metabolite profiling technique for Chlamydomonas reinhardtii cells for
      multiparallel analysis of low-molecular weight polar compounds was developed. The
      experimental protocol was optimized to quickly inactivate enzymatic activity,
      achieve maximum extraction capacity, and process large sample quantities. As a
      result of the rapid sampling, extraction, and analysis by gas chromatography
      coupled to time-of-flight mass spectrometry, more than 800 analytes from a single
      sample could be measured, of which more than 100 could be identified. Analyte
      responses could be determined mostly with ses less than 10%. Wild-type cells of
      C. reinhardtii strain CC-125 subjected to nitrogen-, phosphorus-, sulfur-, or
      iron-depleted growth conditions develop highly distinctive metabolite profiles.
      Individual metabolites undergo marked changes in their steady-state levels.
      Compared to control conditions, sulfur-depleted cells accumulated 4
      hydroxyproline more than 50-fold, whereas the amount of 2-ketovaline was reduced
      to 2% of control levels. The contribution of each compound to the differences
      observed in the metabolic phenotypes is summarized in a quantitatively rigorous
      way by principal component analysis, which clearly discriminates the cells from
      different growth regimes and indicates that phosphorus-depleted conditions induce
      a deficiency syndrome quite different from the response to nitrogen, sulfur, or
      iron starvation.

PMID- 16306141
TI  - Expression profile of two storage-protein gene families in hexaploid wheat
      revealed by large-scale analysis of expressed sequence tags.
AB  - To discern expression patterns of individual storage-protein genes in hexaploid
      wheat (Triticum aestivum cv Chinese Spring), we analyzed comprehensive expressed
      sequence tags (ESTs) of common wheat using a bioinformatics technique. The gene
      families for alpha/beta-gliadins and low molecular-weight glutenin subunit were
      selected from the EST database. The alignment of these genes enabled us to trace
      the single nucleotide polymorphism sites among both genes. The combinations of
      single nucleotide polymorphisms allowed us to assign haplotypes into their
      homoeologous chromosomes by allele-specific PCR. Phylogenetic analysis of these
      genes showed that both storage-protein gene families rapidly diverged after
      differentiation of the three genomes (A, B, and D). Expression patterns of these
      genes were estimated based on the frequencies of ESTs. The storage-protein genes
      were expressed only during seed development stages. The alpha/beta-gliadin genes
      exhibited two distinct expression patterns during the course of seed maturation:
      early expression and late expression. Although the early expression genes among
      the alpha/beta-gliadin and low molecular-weight glutenin subunit genes showed
      similar expression patterns, and both genes from the D genome were preferentially
      expressed rather than those from the A or B genome, substantial expression of two
      early expression genes from the A genome was observed. The phylogenetic
      relationships of the genes and their expression patterns were not correlated.
      These lines of evidence suggest that expression of the two storage-protein genes
      is independently regulated, and that the alpha/beta-gliadin genes possess novel
      regulation systems in addition to the prolamin box.

PMID- 16306142
TI  - Identification, expression, and evolutionary analyses of plant lipocalins.
AB  - Lipocalins are a group of proteins that have been characterized in bacteria,
      invertebrate, and vertebrate animals. However, very little is known about plant
      lipocalins. We have previously reported the cloning of the first true plant
      lipocalins. Here we report the identification and characterization of plant
      lipocalins and lipocalin-like proteins using an integrated approach of data
      mining, expression studies, cellular localization, and phylogenetic analyses.
      Plant lipocalins can be classified into two groups, temperature-induced
      lipocalins (TILs) and chloroplastic lipocalins (CHLs). In addition, violaxanthin
      de-epoxidases (VDEs) and zeaxanthin epoxidases (ZEPs) can be classified as
      lipocalin-like proteins. CHLs, VDEs, and ZEPs possess transit peptides that
      target them to the chloroplast. On the other hand, TILs do not show any targeting
      peptide, but localization studies revealed that the proteins are found at the
      plasma membrane. Expression analyses by quantitative real-time PCR showed that
      expression of the wheat (Triticum aestivum) lipocalins and lipocalin-like
      proteins is associated with abiotic stress response and is correlated with the
      plant's capacity to develop freezing tolerance. In support of this correlation,
      data mining revealed that lipocalins are present in the desiccation-tolerant red
      algae Porphyra yezoensis and the cryotolerant marine yeast Debaryomyces hansenii,
      suggesting a possible association with stress-tolerant organisms. Considering the
      plant lipocalin properties, tissue specificity, response to temperature stress,
      and their association with chloroplasts and plasma membranes of green leaves, we
      hypothesize a protective function of the photosynthetic system against
      temperature stress. Phylogenetic analyses suggest that TIL lipocalin members in
      higher plants were probably inherited from a bacterial gene present in a
      primitive unicellular eukaryote. On the other hand, CHLs, VDEs, and ZEPs may have
      evolved from a cyanobacterial ancestral gene after the formation of the
      cyanobacterial endosymbiont from which the chloroplast originated.

PMID- 16306143
TI  - Subcellular localization and light-regulated expression of protoporphyrinogen IX
      oxidase and ferrochelatase in Chlamydomonas reinhardtii.
AB  - Protoporphyrinogen IX oxidase (PPO) catalyzes the last common step in chlorophyll
      and heme synthesis, and ferrochelatase (FeC) catalyzes the last step of the heme
      synthesis pathway. In plants, each of these two enzymes is encoded by two or more
      genes, and the enzymes have been reported to be located in the chloroplasts or in
      the mitochondria. We report that in the green alga Chlamydomonas reinhardtii, PPO
      and FeC are each encoded by a single gene. Phylogenetic analysis indicates that
      C. reinhardtii PPO and FeC are most closely related to plant counterparts that
      are located only in chloroplasts. Immunoblotting results suggest that C.
      reinhardtii PPO and FeC are targeted exclusively to the chloroplast, where they
      are associated with membranes. These results indicate that cellular needs for
      heme in this photosynthetic eukaryote can be met by heme that is synthesized in
      the chloroplast. It is proposed that the multiplicity of genes for PPO and FeC in
      higher plants could be related to differential expression in differently
      developing tissues rather than to targeting of different gene products to
      different organelles. The FeC content is higher in C. reinhardtii cells growing
      in continuous light than in cells growing in the dark, whereas the content of PPO
      does not significantly differ in light- and dark-grown cells. In cells
      synchronized to a light/dark cycle, the level of neither enzyme varied
      significantly with the phase of the cycle. These results indicate that heme
      synthesis is not directly regulated by the levels of PPO and FeC in C.
      reinhardtii.

PMID- 16306144
TI  - Sensing of inorganic carbon limitation in Synechococcus PCC7942 is correlated
      with the size of the internal inorganic carbon pool and involves oxygen.
AB  - Freshwater cyanobacteria are subjected to large seasonal fluctuations in the
      availability of nutrients, including inorganic carbon (Ci). We are interested in
      the regulation of the CO2-concentrating mechanism (CCM) in the model freshwater
      cyanobacterium Synechococcus sp. strain PCC7942 in response to Ci limitation;
      however, the nature of Ci sensing is poorly understood. We monitored the
      expression of high-affinity Ci-transporter genes and the corresponding induction
      of a high-affinity CCM in Ci-limited wild-type cells and a number of CCM mutants.
      These genotypes were subjected to a variety of physiological and pharmacological
      treatments to assess whether Ci sensing might involve monitoring of fluctuations
      in the size of the internal Ci pool or, alternatively, the activity of the
      photorespiratory pathway. These modes of Ci sensing are congruent with previous
      results. We found that induction of a high-affinity CCM correlates most closely
      with a depletion of the internal Ci pool, but that full induction of this
      mechanism also requires some unresolved oxygen-dependent process.

PMID- 16306145
TI  - Cell expansion and endoreduplication show a large genetic variability in pericarp
      and contribute strongly to tomato fruit growth.
AB  - Postanthesis growth of tomato (Solanum lycopersicon) as of many types of fruit
      relies on cell division and cell expansion, so that some of the largest cells to
      be found in plants occur in fleshy fruit. Endoreduplication is known to occur in
      such materials, which suggests its involvement in cell expansion, although no
      data have demonstrated this hypothesis as yet. We have analyzed pattern
      formation, cell size, and ploidy in tomato fruit pericarp. A first set of data
      was collected in one cherry tomato line throughout fruit development. A second
      set of data was obtained from 20 tomato lines displaying a large weight range in
      fruit, which were compared as ovaries at anthesis and as fully grown fruit at
      breaker stage. A remarkable conservation of pericarp pattern, including cell
      layer number and cell size, is observed in all of the 20 tomato lines at
      anthesis, whereas large variations of growth occur afterward. A strong, positive
      correlation, combining development and genetic diversity, is demonstrated between
      mean cell size and ploidy, which holds for mean cell diameters from 10 to 350
      microm (i.e. a 32,000-times volume variation) and for mean ploidy levels from 3
      to 80 C. Fruit weight appears also significantly correlated with cell size and
      ploidy. These data provide a framework of pericarp patterning and growth. They
      strongly suggest the quantitative importance of polyploidy-associated cell
      expansion as a determinant of fruit weight in tomato.

PMID- 16306146
TI  - Pathogen-responsive expression of glycosyltransferase genes UGT73B3 and UGT73B5
      is necessary for resistance to Pseudomonas syringae pv tomato in Arabidopsis.
AB  - The genome sequencing of Arabidopsis (Arabidopsis thaliana) has revealed that
      secondary metabolism plant glycosyltransferases (UGTs) are encoded by an
      unexpectedly large multigenic family of 120 members. Very little is known about
      their actual function in planta, in particular during plant pathogen
      interactions. Among them, members of the group D are of particular interest since
      they are related to UGTs involved in stress-inducible responses in other plant
      species. We provide here a detailed analysis of the expression profiles of this
      group of Arabidopsis UGTs following infection with Pseudomonas syringae pv tomato
      or after treatment with salicylic acid, methyljasmonate, and hydrogen peroxide.
      Members of the group D displayed distinct induction profiles, indicating
      potential roles in stress or defense responses notably for UGT73B3 and UGT73B5.
      Analysis of UGT expression in Arabidopsis defense-signaling mutants further
      revealed that their induction is methyljasmonate independent, but partially
      salicylic acid dependent. T-DNA tagged mutants (ugt73b3 and ugt73b5) exhibited
      decreased resistance to P. syringae pv tomato-AvrRpm1, indicating that expression
      of the corresponding UGT genes is necessary during the hypersensitive response.
      These results emphasize the importance of plant secondary metabolite UGTs in
      plant-pathogen interactions and provide foundation for future understanding of
      the exact role of UGTs during the hypersensitive response.

PMID- 16306147
TI  - Involvement of PPS3 phosphorylated by elicitor-responsive mitogen-activated
      protein kinases in the regulation of plant cell death.
AB  - Mitogen-activated protein kinase (MAPK) cascades play pivotal roles in plant
      innate immunity. Overexpression of StMEK1(DD), a constitutively active MAPK
      kinase that activates salicylic acid-induced protein kinase (SIPK) and wound
      induced protein kinase (WIPK), provokes hypersensitive response-like cell death
      in Nicotiana benthamiana. Here we purified a 51-kD MAPK, which was activated in
      potato (Solanum tuberosum) tubers treated with hyphal wall elicitor of a plant
      pathogen, and isolated the cDNA designated StMPK1. The deduced amino acid
      sequence of the StMPK1 showed strong similarity to stress-responsive MAPKs, such
      as tobacco (Nicotiana tabacum) SIPK and Arabidopsis (Arabidopsis thaliana)
      AtMPK6. To investigate the downstream signaling of StMPK1, we identified several
      proteins phosphorylated by StMPK1 (PPSs) using an in vitro expression cloning
      method. To dissect the biological function of PPSs in the plant defense, we
      employed virus-induced gene silencing (VIGS) in N. benthamiana. VIGS of NbPPS3
      significantly delayed cell death induced by the transient expression of
      StMEK1(DD) and treatment with hyphal wall elicitor. Furthermore, the mobility
      shift of NbPPS3 on SDS-polyacrylamide gel was induced by transient expression of
      StMEK1(DD). The mobility shift of NbPPS3 induced by StMEK1(DD) was not
      compromised by VIGS of WIPK or SIPK alone, but drastically reduced by the
      silencing of both WIPK and SIPK. This work strongly supports the idea that PPS3
      is a physiological substrate of StMPK1 and is involved in cell death activated by
      a MAPK cascade.

PMID- 16306149
TI  - Hematopoiesis from human embryonic stem cells: overcoming the immune barrier in
      stem cell therapies.
AB  - The multipotency and proliferative capacity of human embryonic stem cells (hESCs)
      make them a promising source of stem cells for transplant therapies and of vital
      importance given the shortage in organ donation. Recent studies suggest some
      immune privilege associated with hESC-derived tissues. However, the adaptability
      of the immune system makes it unlikely that fully differentiated tissues will
      permanently evade immune rejection. One promising solution is to induce a state
      of immune tolerance to a hESC line using tolerogenic hematopoietic cells derived
      from it. This could provide acceptance of other differentiated tissues from the
      same line. However, this approach will require efficient multilineage
      hematopoiesis from hESCs. This review proposes that more efficient
      differentiation of hESCs to the tolerogenic cell types required is most likely to
      occur through applying knowledge gained of the ontogeny of complex regulatory
      signals used by the embryo for definitive hematopoietic development in vivo.
      Stepwise formation of mesoderm, induction of definitive hematopoietic stem cells,
      and the application of factors key to their self-renewal may improve in vitro
      production both quantitatively and qualitatively.

PMID- 16306148
TI  - Novel markers of xylogenesis in zinnia are differentially regulated by auxin and
      cytokinin.
AB  - The characterization of in vitro xylogenic cultures of zinnia (Zinnia elegans)
      has led to major discoveries in the understanding of xylem formation in plants.
      We have constructed and characterized a subtractive library from zinnia cultures
      enriched in genes that are specifically expressed at the onset of secondary wall
      deposition and tracheary element (TE) programmed cell death. This Late
      Xylogenesis Library (LXL) consisted of 236 nonredundant cDNAs, 77% of which
      encoded novel sequences in comparison with the 17,622 expressed sequence tag
      sequences publicly available. cDNA arrays were constructed to examine dynamic
      global gene expression during the course of TE formation. As a first step in
      dissecting auxin and cytokinin signaling during TE differentiation, macroarrays
      were probed with cDNAs from cells cultured in different hormonal conditions.
      Fifty-one percent of the LXL genes were induced by either auxin or cytokinin
      individually, the large majority by auxin. To determine the potential involvement
      of these categories of genes in TE differentiation, multiplex in situ-reverse
      transcription-PCR was performed on cells for two genes encoding putative cell
      wall proteins: Gibberellin stimulated transcript-1, induced by auxin alone, and
      expansin 5, induced by cytokinin alone. All transcriptionally active TEs
      expressed both genes, indicating that, although these genes may not be considered
      as specific markers for TE differentiation per se, they are nevertheless an
      integral part of TE differentiation program. Among the non-TE population, four
      different gene expression-based cell types could be distinguished. Together,
      these results demonstrate the underlying complexity of hormonal perception and
      the existence of several different cell types in in vitro TE cell cultures.

PMID- 16306150
TI  - The role of the hyaluronan receptor CD44 in mesenchymal stem cell migration in
      the extracellular matrix.
AB  - In a previous investigation, we demonstrated that mesenchymal stem cells (MSCs)
      actively migrated to cardiac allografts and contributed to graft fibrosis and, to
      a lesser extent, to myocardial regeneration. The cellular/molecular mechanism
      responsible for MSC migration, however, is poorly understood. This paper examines
      the role of CD44-hyaluronan interaction in MSC migration, using a rat MSC line
      Ap8c3 and mouse CD44-/- or CD44+/+ bone marrow stromal cells (BMSCs). Platelet
      derived growth factor (PDGF) stimulation of MSC Ap8c3 cells significantly
      increased the levels of cell surface CD44 detected by flow cytometry. The CD44
      standard isoform was predominantly expressed by Ap8c3 cells, accounting for 90%
      of the CD44 mRNA determined by quantitative real-time polymerase chain reaction.
      Mouse CD44-/- BMSCs bonded inefficiently to hyaluronic acid (HA), whereas CD44+/+
      BMSC and MSC Ap8c3 adhered strongly to HA. Adhesions of MSC Ap8c3 cells to HA
      were suppressed by anti-CD44 antibody and by CD44 small interfering RNA (siRNA).
      HA coating of the migration chamber significantly promoted passage of CD44+/+
      BMSC or Ap8c3 cells, but not CD44-/- BMSCs, through the insert membranes (p <
      .01). Migration of MSC Ap8c3 was significantly inhibited by anti-CD44 antibodies
      (p < .01) and to a lesser extent by CD44 siRNA (p = .05). The data indicate that
      MSC Ap8c3 cells, in response to PDGF stimulation, express high levels of CD44
      standard (CD44s) isoform, which facilitates cell migration through interaction
      with extracellular HA. Such a migratory mechanism could be critical for
      recruitment of MSCs into wound sites for the proposition of tissue regeneration,
      as well as for migration of fibroblast progenitors to allografts in the
      development of graft fibrosis.

PMID- 16306151
TI  - Mycotoxin patulin activates the p38 kinase and JNK signaling pathways in human
      embryonic kidney cells.
AB  - Patulin (PAT), a mycotoxin mainly produced by Penicillium and Aspergillus, is
      frequently detected in moldy fruits and fruit products. Exposure of human
      embryonic kidney (HEK293) cells to PAT led to a dose- and time-dependent increase
      in the phosphorylation of two major mitogen-activated protein kinases (MAPKs),
      p38 kinase and c-Jun N-terminal kinase (JNK). The phosphorylated forms of MAPK
      kinase 4 (MKK4), c-Jun, and ATF-2 were also seen in PAT-treated cultures. The
      cell death caused by PAT was significantly reduced by the p38 kinase inhibitor,
      SB203580, but not by the JNK inhibitor, SP600125. Neither p38 kinase nor JNK
      played a role in the PAT-induced DNA damage. In PAT-treated cells, inactivation
      of double-stranded RNA-activated protein kinase R (PKR) by the inhibitor,
      adenine, markedly suppressed JNK and ERK phosphorylation. Treatment of HEK293
      cells with PAT-cysteine adduct, a chemical derivative of PAT, showed no effect on
      MAPK signaling pathways, cell viability, or DNA integrity. These results indicate
      that PAT causes rapid activation of p38 kinase and JNK in HEK293 cells, but only
      the p38 kinase signaling pathway contributes to the PAT-induced cell death. PKR
      also plays a role in PAT-mediated MAPK activation.

PMID- 16306152
TI  - Diffusion tensor imaging and voxel based morphometry study in early progressive
      supranuclear palsy.
AB  - BACKGROUND: A comprehensive characterisation of grey and white matter changes in
      progressive supranuclear palsy (PSP), the second most common extrapyramidal
      syndrome after Parkinson disease, is still not available. OBJECTIVE: To evaluate
      grey and white matter changes in mild PSP patients by voxel based morphometry
      (VBM) and diffusion tensor imaging (DTI), respectively. METHODS: 14 mild PSP
      patients and 14 healthy controls entered the study and underwent a clinical and
      neuropsychological evaluation according with a standardised assessment. Each
      subject had a structural magnetic resonance imaging (MRI) study. Processing
      analysis of MRI data was carried out according to optimised VBM and fractional
      anisotropy was determined. RESULTS: Compared with the controls, in PSP patients
      VBM analysis showed a significant clusters of reduced grey matter in premotor
      cortex, frontal operculum, anterior insula, hippocampus, and parahippocampal
      gyrus, bilaterally. With regard to subcortical brain regions, the pulvinar,
      dorsomedial and anterior nuclei of the thalamus, and superior and inferior
      culliculum were affected bilaterally. A bilateral decrease in fractional
      anisotropy in superior longitudinal fasciculus, anterior part of corpus callosum,
      arcuate fascicolus, posterior thalamic radiations, and internal capsule, probably
      involving the cortico-bulbar tracts, was present in PSP patients. CONCLUSIONS:
      These data provide evidence for both grey and white matter degeneration in PSP
      from the early disease stage. These structural changes suggest that atrophy of
      cortical and subcortical structures and neurodegeneration of specific fibre
      tracts contribute to neurological deficits in PSP.

PMID- 16306153
TI  - Hippocampal atrophy on MRI in frontotemporal lobar degeneration and Alzheimer's
      disease.
AB  - BACKGROUND: Hippocampal atrophy on magnetic resonance imaging (MRI) is an early
      characteristic of Alzheimer's disease. However, hippocampal atrophy may also
      occur in other dementias, such as frontotemporal lobar degeneration (FTLD).
      OBJECTIVE: To investigate hippocampal atrophy on MRI in FTLD and its three
      clinical subtypes, in comparison with Alzheimer's disease, using volumetry and a
      visual rating scale. METHODS: 42 patients with FTLD (17 frontotemporal dementia,
      13 semantic dementia, and 12 progressive non-fluent aphasia), 103 patients with
      Alzheimer's disease, and 73 controls were included. Hippocampal volumetry and the
      easily applicable medial temporal lobe atrophy (MTA) rating scale were applied to
      assess hippocampal atrophy. RESULTS: Multivariate analysis of variance for
      repeated measures showed an effect of diagnostic group on hippocampal volume.
      There was a significant diagnosis by side (left v right) interaction. Both FTLD
      and Alzheimer's disease showed hippocampal atrophy compared with controls.
      Results of the visual MTA rating scale confirmed these findings. Within the FTLD
      subtypes there were marked differences in hippocampal atrophy. Frontotemporal
      dementia and semantic dementia showed bilateral hippocampal atrophy, and in
      semantic dementia the left hippocampus was smaller than in Alzheimer's disease.
      No significant hippocampal atrophy was detected in non-fluent progressive
      aphasia. CONCLUSIONS: Hippocampal atrophy is not only a characteristic of
      Alzheimer's disease but also occurs in FTLD. The three clinical subtypes of FTLD
      show different patterns of hippocampal atrophy.

PMID- 16306154
TI  - Clinical trials in mild cognitive impairment: lessons for the future.
AB  - Mild cognitive impairment (MCI) is an operational definition for a cognitive
      decline in individuals with a greater risk of developing dementia. The amnestic
      subtype of MCI is of particular interest because these individuals most likely
      progress to Alzheimer's disease (AD). Currently hypothesised therapeutic
      approaches in MCI are mainly based on AD treatment strategies. Long term
      secondary prevention randomised clinical trials have been completed in amnestic
      MCI populations, encompassing agents with various mechanisms of action:
      acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine),
      antioxidants (vitamin E), anti-inflammatories (rofecoxib), and nootropics
      (piracetam). The design of clinical trials in MCI is influenced by study
      objectives and definition of primary end points: time to clinical diagnosis of
      dementia, and AD in particular, or symptom progression. As none of the drugs
      previously shown to have clinical efficacy in AD trials or benefit in everyday
      practice have met the primary objectives of the respective trials, design of
      future clinical trials in MCI should be further developed particularly as regards
      the selection of more homogeneous samples at entry, optimal treatment duration,
      and multidimensional and reliable outcomes.

PMID- 16306155
TI  - Origin of ICU acquired paresis determined by direct muscle stimulation.
AB  - BACKGROUND: Acquired diffuse paresis in an intensive care unit (ICU) can result
      from critical illness myopathy or polyneuropathy. Clinical examination and
      conventional neurophysiological techniques may not distinguish between these
      entities. OBJECTIVE: To assess the value of direct muscle stimulation (DMS) to
      differentiate myopathic from neuropathic process in critically ill patients with
      diffuse severe muscle weakness. METHODS: 30 consecutive patients with ICU
      acquired diffuse motor weakness were studied. Responses of the right deltoid and
      tibialis anterior muscles to DMS and to motor nerve stimulation (MNS) were
      studied and compared with results of conventional nerve conduction studies and
      concentric needle electromyography (EMG). An original algorithm was used for
      differential diagnosis, taking into account first the amplitude of the responses
      to DMS, then the MNS to DMS amplitude ratio, and finally the amplitude of the
      sensory nerve action potentials recorded at the lower limbs. RESULTS: Evidence of
      neuropathy and myopathy was found in 57% and 83% of the patients, respectively.
      Pure or predominant myopathy was found in 19 patients. Other results were
      consistent with neuromyopathy (n = 5) and pure or predominant neuropathy (n = 2).
      Four patients had normal results with stimulation techniques, but spontaneous EMG
      activity and raised plasma creatine kinase suggesting necrotic myopathy.
      CONCLUSIONS: A neurophysiological approach combining DMS and conventional
      techniques revealed myopathic processes in a majority of ICU patients. Reduced
      muscle fibre excitability may be a leading cause for this. The diagnosis of
      myopathy in ICU acquired paralysis can be established by a combination of DMS,
      needle EMG, and plasma creatine kinase.

PMID- 16306156
TI  - Interinstitutional variance of postoperative radiotherapy and follow up for
      meningiomas in Germany: impact of changes of the WHO classification.
AB  - OBJECTIVE: To document and critically analyse the impact of the revised WHO 2000
      histological classification for meningiomas on postoperative
      radiotherapy/radiosurgery indications and MRI follow up protocols. METHODS: The
      current (2000) WHO classification was used to grade 57 meningiomas treated
      surgically at one institution. These had been reviewed previously in 1999. All
      German neurosurgical departments carrying out intracranial microsurgery were
      asked to detail their guidelines for radiation therapy and follow up for
      meningiomas of different WHO grades. RESULTS: Use of the current criteria
      downgraded seven of 15 atypical meningiomas (WHO grade II, MII) to grade I (MI),
      and four of six anaplastic tumours (WHO grade III, MIII) to grade II. Indications
      for radiotherapy/radiosurgery and MRI follow up protocols varied substantially
      with the histological grade and between institutions--for example, after an
      incomplete resection, radiotherapy/radiosurgery recommendations differed between
      MI and MII in 30 of 58 units (52%), and between MII and MIII in 34 of 56 units
      (61%). CONCLUSIONS: Correlative studies combining treatment and outcome data with
      a standardised histopathological analysis are warranted to define properly the
      indications for radiotherapy/radiosurgery and follow up protocols after surgery
      for meningiomas of different histological grades. The use of changing grading
      paradigms during recent years renders decision making based on local and
      published experience difficult. The relatively large number of meningiomas
      classified as atypical/WHO grade II in current practice would argue against an
      uncritically aggressive approach to these tumours.

PMID- 16306158
TI  - Adjuvant chemotherapy for colon cancer: a confusing area!

PMID- 16306159
TI  - Age-associated decrease in contraction-induced activation of downstream targets
      of Akt/mTor signaling in skeletal muscle.
AB  - In this study, we investigated the effect of age on the association of eukaryotic
      initiation factor 4E (eIF4E) with eukaryotic initiation factor 4G (eIF4G), as
      well as the activity of its binding protein (4E-BP1) and the activity of glycogen
      synthase kinase-3 (GSK-3) after a single bout of rat hindlimb muscle contractile
      activity elicited by high-frequency electrical stimulation (HFES) of the sciatic
      nerve. Tibialis anterior (TA) and plantaris (Pla) muscles from adult (Y; 6 mo
      old) and aged (O; 30 mo old) Fischer 344 x Brown Norway rats were collected
      immediately or 6 h after HFES. eIF4E-eIF4G association was elevated at 6 h of
      recovery in TA (1.9 +/- 0.2-fold, P < 0.05) and immediately and 6 h after
      exercise in Pla (2.1 +/- 0.3- and 2.1 +/- 0.7-fold, P < 0.05) in Y rats. No
      significant increase was observed in O rats. An increase in 4E-BP1
      phosphorylation was observed only 6 h after HFES in TA (5.0 +/- 2.0-fold, P <
      0.05) in Y rats. Phosphorylation of GSK-3alpha was increased immediately and 6 h
      after contraction in TA (1.6 +/- 0.3- and 4.1 +/- 0.8-fold, P < 0.05) and Pla
      (1.7 +/- 0.2- and 2.1 +/- 0.4-fold, P < 0.05) in Y rats and remained unaffected
      in O rats. Phosphorylation of GSK-3beta was observed only immediately after HFES
      in TA (1.5 +/- 0.2-fold, P < 0.05) in Y rats. Overall, eIF4E-eIF4G association
      and phosphorylation of 4E-BP1 and GSK-3 are increased after HFES in adult, but
      not in aged, animals. These observations suggest that the anabolic response to
      muscle stimulation is attenuated with aging and may contribute to the limited
      capacity of hypertrophy in aged animals.

PMID- 16306160
TI  - Do chronic primary insomniacs have impaired heat loss when attempting sleep?
AB  - For good sleepers, distal skin temperatures (e.g., hands and feet) have been
      shown to increase when sleep is attempted. This process is said to reflect the
      body's action to lose heat from the core via the periphery. However, little is
      known regarding whether the same process occurs for insomniacs. It would be
      expected that insomniacs would have restricted heat loss due to anxiety when
      attempting sleep. The present study compared the finger skin temperature changes
      when sleep was attempted for 11 chronic primary insomniacs [mean age = 40.0 years
      (SD 13.3)] and 8 good sleepers [mean age = 38.6 years (SD 13.2)] in a 26-h
      constant routine protocol with the inclusion of multiple-sleep latency tests.
      Contrary to predictions, insomniacs demonstrated increases in finger skin
      temperature when attempting sleep that were significantly greater than those in
      good sleepers (P = 0.001), even though there was no significant differences in
      baseline finger temperature (P = 0.25). These significant increases occurred
      despite insomniacs reporting significantly greater sleep anticipatory anxiety (P
      < 0.0008). Interestingly, the core body temperature mesor of insomniacs (37.0 +/-
      0.2 degrees C) was significantly higher than good sleepers (36.8 +/- 0.2 degrees
      C; P = 0.03). Whether insomniacs could have impaired heat loss that is masked by
      elevated heat production is discussed.

PMID- 16306161
TI  - Baroreflex modulation by angiotensins at the rat rostral and caudal ventrolateral
      medulla.
AB  - We determined the effect of microinjection of ANG-(1-7) and ANG II into two key
      regions of the medulla that control the circulation [rostral and caudal
      ventrolateral medulla (RVLM and CVLM, respectively)] on baroreflex control of
      heart rate (HR) in anesthetized rats. Reflex bradycardia and tachycardia were
      induced by increases and decreases in mean arterial pressure produced by
      intravenous phenylephrine and sodium nitroprusside, respectively. The pressor
      effects of ANG-(1-7) and ANG II (25 pmol) after RVLM microinjection (11 +/- 0.8
      and 10 +/- 2 mmHg, respectively) were not accompanied by consistent changes in
      HR. In addition, RVLM microinjection of these angiotensin peptides did not alter
      the bradycardic or tachycardic component of the baroreflex. CVLM microinjections
      of ANG-(1-7) and ANG II produced hypotension (-11 +/- 1.5 and -11 +/- 1.9 mmHg,
      respectively) that was similarly not accompanied by significant changes in HR.
      However, CVLM microinjections of angiotensins induced differential changes in the
      baroreflex control of HR. ANG-(1-7) attenuated the baroreflex bradycardia (0.26
      +/- 0.06 ms/mmHg vs. 0.42 +/- 0.08 ms/mmHg before treatment) and facilitated the
      baroreflex tachycardia (0.86 +/- 0.19 ms/mmHg vs. 0.42 +/- 0.10 ms/mmHg before
      treatment); ANG II produced the opposite effect, attenuating baroreflex
      tachycardia (0.09 +/- 0.06 ms/mmHg vs. 0.31 +/- 0.07 ms/mmHg before treatment)
      and facilitating the baroreflex bradycardia (0.67 +/- 0.16 ms/mmHg vs. 0.41 +/-
      0.05 ms/mmHg before treatment). The modulatory effect of ANG II and ANG-(1-7) on
      baroreflex sensitivity was completely abolished by peripheral administration of
      methylatropine. These results suggest that ANG II and ANG-(1-7) at the CVLM
      produce a differential modulation of the baroreflex control of HR, probably
      through distinct effects on the parasympathetic drive to the heart.

PMID- 16306162
TI  - Differential effects of water and saline intake on water deprivation-induced c
      Fos staining in the rat.
AB  - We studied c-Fos staining in adult male rats after 48 h of water deprivation and
      after 46 h of water deprivation with 2 h of access to water or physiological
      saline. Controls were allowed ad libitum access to water and physiological
      saline. For immunocytochemistry, anesthetized rats were perfused with a
      commercially available antibody for c-Fos. Dehydration significantly increased
      plasma vasopressin (AVP), osmolality, plasma renin activity (PRA), hematocrit,
      and sodium concentration and decreased urinary volume. Fos staining was
      significantly increased in the median preoptic nucleus, organum vasculosum of the
      lamina terminalis, supraoptic nucleus (SON), and magnocellular and parvocellular
      paraventricular nucleus (PVN), as well as the area postrema, nucleus of the
      solitary tract (NTS), and rostral ventrolateral medulla (RVL). Rehydration with
      water significantly decreased AVP levels and Fos staining in the SON, PVN, and
      RVL and significantly increased Fos expression in the perinuclear zone of the
      SON, NTS, and parabrachial nucleus. Rehydration with water was associated with
      decreased urinary sodium concentration and hypotonicity, and hematocrit and PRA
      were comparable to levels seen after dehydration. After rehydration with saline,
      plasma osmolality, hematocrit, and PRA were not different from control, but
      plasma AVP and urinary sodium concentration were increased. In the SON, Fos
      staining was significantly increased, with a great percentage of the Fos cells
      also stained for oxytocin compared with water deprivation. Changes in Fos
      staining were also observed in the NTS, RVL, parabrachial nucleus, and PVN.
      Rehydration with water or saline produces differential effects on plasma AVP, Fos
      staining, and sodium concentration.

PMID- 16306163
TI  - Cerebral blood flow during orthostasis: role of arterial CO2.
AB  - Reductions in end-tidal Pco(2) (Pet(CO(2))) during upright posture have been
      suggested to be the result of hyperventilation and the cause of decreases in
      cerebral blood flow (CBF). The goal of this study was to determine whether
      decreases in Pet(CO(2)) reflected decreases in arterial Pco(2) (Pa(CO(2))) and
      their relation to increases in alveolar ventilation (Va) and decreases in CBF.
      Fifteen healthy subjects (10 women and 5 men) were subjected to a 10-min head-up
      tilt (HUT) protocol. Pa(CO(2)), Va, and cerebral flow velocity (CFV) in the
      middle and anterior cerebral arteries were examined. In 12 subjects who completed
      the protocol, reductions in Pet(CO(2)) and Pa(CO(2)) (-1.7 +/- 0.5 and -1.1 +/-
      0.4 mmHg, P < 0.05) during minute 1 of HUT were associated with a significant
      increase in Va (+0.7 +/- 0.3 l/min, P < 0.05). However, further decreases in
      Pa(CO(2)) (-0.5 +/- 0.5 mmHg, P < 0.05), from minute 1 to the last minute of HUT,
      occurred even though Va did not change significantly (-0.2 +/- 0.3 l/min, P = not
      significant). Similarly, CFV in the middle and anterior cerebral arteries
      decreased (-7 +/- 2 and -8 +/- 2%, P < 0.05) from minute 1 to the last minute of
      HUT, despite minimal changes in Pa(CO(2)). These data suggest that decreases in
      Pet(CO(2)) and Pa(CO(2)) during upright posture are not solely due to increased
      Va but could be due to ventilation-perfusion mismatch or a redistribution of
      CO(2) stores. Furthermore, the reduction in Pa(CO(2)) did not fully explain the
      decrease in CFV throughout HUT. These data suggest that factors in addition to a
      reduction in Pa(CO(2)) play a role in the CBF response to orthostatic stress.

PMID- 16306164
TI  - Challenging the sleep homeostat does not influence the thermoregulatory system in
      men: evidence from a nap vs. sleep-deprivation study.
AB  - The purpose of our study was to understand the relationship between the
      components of the three-process model of sleepiness regulation (homeostatic,
      circadian, and sleep inertia) and the thermoregulatory system. This was achieved
      by comparing the impact of a 40-h sleep deprivation vs. a 40-h multiple nap
      paradigm (10 cycles with 150/75 min wakefulness/sleep episodes) on distal and
      proximal skin temperatures, core body temperature (CBT), melatonin secretion,
      subjective sleepiness, and nocturnal sleep EEG slow-wave activity in eight
      healthy young men in a "controlled posture" protocol. The main finding of the
      study was that accumulation of sleep pressure increased subjective sleepiness and
      slow-wave activity during the succeeding recovery night but did not influence the
      thermoregulatory system as measured by distal, proximal, and CBT. The circadian
      rhythm of sleepiness (and proximal temperature) was significantly correlated and
      phase locked with CBT, whereas distal temperature and melatonin secretion were
      phase advanced (by 113 +/- 28 and 130 +/- 30 min, respectively; both P < 0.005).
      This provides evidence for a primary role of distal vasodilatation in the
      circadian regulation of CBT and its relationship with sleepiness. Specific
      thermoregulatory changes occur at lights off and on. After lights off, skin
      temperatures increased and were most pronounced for distal; after lights on, the
      converse occurred. The decay in distal temperature (vasoconstriction) was
      significantly correlated with the disappearance of sleep inertia. These effects
      showed minor and nonsignificant circadian modulation. In summary, the
      thermoregulatory system seems to be independent of the sleep homeostat, but the
      circadian modulation of sleepiness and sleep inertia is clearly associated with
      thermoregulatory changes.

PMID- 16306165
TI  - Na(+)-D-glucose cotransporter in the kidney of Squalus acanthias: molecular
      identification and intrarenal distribution.
AB  - Using primers against conserved regions of mammalian Na(+)-d-glucose
      cotransporters (SGLT), a cDNA was cloned from the kidney of spiny dogfish shark
      (Squalus acanthias). On the basis of comparison of amino acid sequence, membrane
      topology, and putative glycosylation and phosphorylation sites, the cDNA could be
      shown to belong to the family of sglt genes. Indeed, Na(+)-dependent d-glucose
      uptake could be demonstrated after expression of the gene in Xenopus laevis
      oocytes. In a dendrogram, the SGLT from shark kidney has a high homology to the
      mammalian SGLT2. Computer analysis revealed that the elasmobranch protein is most
      similar to the mammalian proteins in the transmembrane regions and contains
      already all the amino acids identified to be functionally important, suggesting
      early conservation during evolution. Extramembraneous loops show larger
      variations. This holds especially for loop 13, which has been implied as a
      phlorizin-binding domain. Antibodies were generated and the intrarenal
      distribution of the SGLT was studied in cryosections. In parallel, the nephron
      segments were identified by lectins. Positive immunoreactions were found in the
      proximal tubule in the early parts PIa and PIb and the late segment PIIb. The
      large PIIa segment of the proximal tubule showed no reaction. In contrast to the
      mammalian kidney also the late distal tubule, the collecting tubule, and the
      collecting duct showed immunoreactivity. The molecular information confirms
      previous vesicle studies in which a low affinity SGLT with a low stoichiometry
      has been observed and supports the notion of a similarity of the shark kidney
      SGLT to the mammalian SGLT2. Despite its presence in the late parts of the
      nephron, the absence of SGLT in the major part of the proximal tubule, the
      relatively low affinity, and in particular the low stoichiometry might explain
      the lack of a T(m) for d-glucose in the shark kidney.

PMID- 16306166
TI  - Therapeutic effect of anti-TNF-alpha antibodies in an experimental model of anti
      neutrophil cytoplasm antibody-associated systemic vasculitis.
AB  - The therapeutic options for anti-neutrophil cytoplasm antibody (ANCA)-associated
      systemic vasculitis (AASV) remain limited and hampered by adverse effects. One
      potential novel therapeutic avenue involves inhibition of TNF-alpha, with
      encouraging uncontrolled data in humans with one agent (infliximab) but
      disappointing controlled data from another (etanercept). For investigating the
      potential role of TNF-alpha as a therapeutic target in AASV, the effect of an
      anti-rat TNF-alpha mAb (CNTO 1081) in a rat model of AASV was investigated. For
      testing the effect of TNF-alpha blockade in this model, starting on day 28 after
      immunization (a point when glomerulonephritis is established), animals were
      randomized to treatment with CNTO 1081 or control mouse IgG. Treatment with CNTO
      1081 significantly reduced albuminuria (mean 1.1 +/- 0.3 mg/24 h CNTO 1081 versus
      8.0 +/- 1.9 controls; P < 0.05) and crescent formation (0% CNTO 1081 versus 60%
      controls; P < 0.05). Lung hemorrhage was also reduced (CNTO 1081: median score 0,
      range 0 to 2; controls: 2, range 1 to 3; P < 0.05). When analyzed by intravital
      microscopy, there was a 43% inhibition of leukocyte transmigration in mesenteric
      venules in response to topical CXCL1 (a neutrophil chemoattractant) in the CNTO
      1081 group compared with controls (P < 0.001). Anti-myeloperoxidase antibody
      titers were similar in both groups throughout the study. In conclusion, these
      findings indicate that TNF-alpha plays an important role in the pathogenesis of
      experimental autoimmune vasculitis and suggest that blockade of this cytokine
      with an mAb is effective in treating established vasculitis. The therapeutic
      action of anti-TNF-alpha reagents may be mediated, in part, by suppression of the
      enhanced leukocyte-endothelial interactions in this disorder.

PMID- 16306167
TI  - Higher peritoneal transport status is associated with higher mortality and
      technique failure in the Australian and New Zealand peritoneal dialysis patient
      populations.
AB  - Although early studies observed that peritoneal membrane transport
      characteristics were determinants of morbidity and mortality in peritoneal
      dialysis (PD) patients, more recent investigations, such as the Ademex trial,
      have refuted these findings. The aim of this study was to determine whether
      baseline peritoneal transport status predicted subsequent survival in Australian
      and New Zealand PD patients. The study included all adult patients in Australia
      and New Zealand who commenced PD between April 1, 1999, and March 31, 2004, and
      had a peritoneal equilibration test (PET) performed within 6 mo of PD
      commencement. Times to death and death-censored technique failure were examined
      by Kaplan-Meier analyses and multivariate Cox proportional hazards models. PET
      measurements were available in 3702 (72%) of the 5170 individuals who began PD
      treatment in Australia or New Zealand during the study period. In these patients,
      high transporter status was found to be a significant, independent predictor of
      death-censored technique failure (adjusted hazard ratio [AHR] 1.23; 95%
      confidence interval [CI] 1.02 to 1.49; P = 0.03) and mortality (AHR 1.34; 95% CI
      1.05 to 1.79, P = 0.02) compared with low-average transport status. High-average
      transport class was also associated with mortality (AHR 1.21; 95% CI 1.00 to
      1.48; P = 0.047) but not death-censored technique failure (AHR 1.04; 95% CI 0.90
      to 1.21) compared with low-average transport status. When transport status was
      alternatively analyzed as a continuous variable, dialysate:plasma creatinine
      ratio at 4 h was independently predictive of both death-censored technique
      failure (AHR 1.07; 95% CI 1.01 to 1.295; P = 0.031) and death (AHR 1.09; 95% CI
      1.01 to 1.373; P = 0.036 per 0.1 change in dialysate:plasma creatinine).
      Peritoneal transport rate is a highly significant risk factor for both mortality
      and death-censored technique failure in the Australian and New Zealand incident
      PD patient populations.

PMID- 16306168
TI  - No difference in degree of interstitial Sirius red-stained area in serial
      biopsies from area under concentration-over-time curves-guided cyclosporine
      versus tacrolimus-treated renal transplant recipients at one year.
AB  - Interstitial fibrosis is the main characteristic of chronic allograft nephropathy
      and long-term graft failure. Cyclosporin (CsA) is thought to be more fibrogenic
      than tacrolimus. In a prospective, randomized, multicenter trial using a
      calcineurin-sparing regimen, renal interstitial volume was compared in CsA- and
      tacrolimus-treated renal transplant recipients by image analysis of Sirius red
      (SR)-stained cortical areas in protocol biopsies obtained at 6 mo (n = 94) and 12
      mo (n = 97) after transplantation. Immunosuppression consisted of CsA or
      tacrolimus, CD25 mAb, mycophenolate mofetil, and prednisolone. CsA therapy
      increased the 6-mo risk for subclinical rejection. The prevalence of subclinical
      rejection was 38.8% in the CsA-treated and 15.2% in the tacrolimus-treated
      patient group (P = 0.012). Strikingly, no difference in the degree of
      interstitial SR-stained area was detectable between the two treatment groups. In
      particular, previous subclinical rejection episodes did not influence the degree
      of interstitial volume. Also, no difference in GFR occurred at 1 yr, when the
      mean GFR mounted 63 ml/min. No significant differences in the degree of
      interstitial SR-stained area could be observed at 6 and 12 mo between CsA- and
      tacrolimus-treated renal transplant recipients. Although CsA-treated patients
      developed significantly more subclinical rejections at 6 mo, this did not
      influence the degree of SR staining or the change in renal function at 1 yr.

PMID- 16306169
TI  - Ghrelin improves renal function in mice with ischemic acute renal failure.
AB  - Growth hormone and IGF-1 have been suggested to have tissue-protective effects.
      Ghrelin is a stomach-derived growth hormone secretagogue. The effects of ghrelin
      on ischemia/reperfusion-induced renal failure in mice were examined. Ischemic
      acute renal failure was induced by bilateral renal artery clamping for 45 min and
      reperfusion for 24 h. Ghrelin (100 microg/kg mouse) or vehicle was injected
      subcutaneously six times before surgery and three times after surgery every 8 h.
      Twenty-four hours after reperfusion, the right kidney was isolated and perfused.
      Acetylcholine (ACh)- and adrenomedullin-induced endothelium-dependent
      vasorelaxation of renal vessels significantly improved in ghrelin-pretreated mice
      (%Delta renal perfusion pressure by 10(-7) M ACh -63.5 +/- 3.7 versus -41.2 +/-
      5.5%; P < 0.05). This change was associated with significant increases of nitric
      oxide release in the kidneys of ghrelin-treated mice (10(-7) M ACh 35.5 +/- 5.8
      versus 16.9 +/- 3.5 fmol/g kidney per min; P < 0.05). Serum concentration of urea
      nitrogen (53 +/- 7 versus 87 +/- 15 mg/dl; P < 0.05) and renal injury score were
      significantly lower in the ghrelin group (2.5 +/- 0.8 versus 5.3 +/- 1.5; P <
      0.01). Tubular apoptotic index was significantly lower in the ghrelin group (5 +/
      5 versus 28 +/- 4; P < 0.05). Furthermore, the survival rate after the 60-min
      ischemic period was higher in the ghrelin group (80 versus 20%; P < 0.05).
      Ghrelin treatment significantly increased the serum level of IGF-1. However, such
      renal protective effects of ghrelin on ischemia/reperfusion injury were not
      observed in insulin receptor substrate-2 knockout mice. These results suggest
      that ghrelin may protect the kidneys from ischemia/reperfusion injury and that
      this effect is related to an improvement of endothelial function through an IGF-1
      mediated pathway.

PMID- 16306170
TI  - Trial-by-trial discrimination of three enantiomer pairs by neural ensembles in
      mammalian olfactory bulb.
AB  - Populations of output neurons in the mammalian olfactory bulb (OB) exhibit
      distinct, widespread spatial and temporal activation patterns when stimulated
      with odorants. However, questions remain as to how ensembles of mitral/tufted
      (M/T) neurons in the mammalian OB represent odorant information. In this report,
      the single-trial encoding limits of random ensembles of putative single- and
      multiunit M/T cells in the anesthetized rat OB during presentations of
      enantiomers of limonene, carvone, and 2-butanol are investigated using
      simultaneous multielectrode recording techniques. The results of these
      experiments are: the individual constituents of our recorded ensembles broadly
      represent information about the presented odorants, the ensemble single-trial
      response of small spatially distributed populations of M/T neurons can readily
      discriminate between six different odorants, and the most consistent odorant
      discrimination is attained when the ensemble consists of all available units and
      their responses are integrated over an entire breathing cycle. These results
      suggest that small differences in spike counts among the ensemble members become
      significant when taken within the context of the entire ensemble. This may
      explain how ensembles of broadly tuned OB neurons contribute to olfactory
      perception and may explain how small numbers of individual units receiving input
      from distinct olfactory receptor neurons can be combined to form a robust
      representation of odorants.

PMID- 16306171
TI  - Control of the subthalamic innervation of substantia nigra pars reticulata by D1
      and D2 dopamine receptors.
AB  - The effects of activating dopaminergic D1 and D2 class receptors of the
      subthalamic projections that innervate the pars reticulata of the subtantia nigra
      (SNr) were explored in slices of the rat brain using the whole cell patch-clamp
      technique. Excitatory postsynaptic currents (EPSCs) that could be blocked by 6
      cyano-7-nitroquinoxalene-2,3-dione and D-(-)-2-amino-5-phosphonopentanoic acid
      were evoked onto reticulata GABAergic projection neurons by local field
      stimulation inside the subthalamic nucleus in the presence of bicuculline. Bath
      application of (RS)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
      hydrochloride (SKF-38393), a dopaminergic D1-class receptor agonist, increased
      evoked EPSCs by approximately 30% whereas the D2-class receptor agonist, trans-(
      )-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo(3,4-g)quinoline
      (quinpirole), reduced EPSCs by approximately 25%. These apparently opposing
      actions were blocked by the specific D1- and D2-class receptor antagonists: R-(+)
      7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetra-hydro-1H-3
      benzazepinehydrochloride (SCH 23390) and S-(-)-5-amino-sulfonyl-N-[(1-ethyl-2
      pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride), respectively. Both effects
      were accompanied by changes in the paired-pulse ratio, indicative of a
      presynaptic site of action. The presynaptic location of dopamine receptors at the
      subthalamonigral projections was confirmed by mean-variance analysis. The effects
      of both SKF-38393 and quinpirole could be observed on terminals contacting the
      same postsynaptic neuron. Sulpiride and SCH 23390 enhanced and reduced the evoked
      EPSC, respectively, suggesting a constitutive receptor activation probably
      arising from endogenous dopamine. These data suggest that dopamine
      presynaptically modulates the subthalamic projection that targets GABAergic
      neurons of the SNr. Implications of this modulation for basal ganglia function
      are discussed.

PMID- 16306172
TI  - Fractal noises and motions in time series of presympathetic and sympathetic
      neural activities.
AB  - We used Allan factor analysis to classify time series of the discharges of single
      presympathetic neurons in the cat medullary lateral tegmental field (LTF) and
      rostral ventrolateral medulla (RVLM) and of the postganglionic vertebral
      sympathetic nerve. These time series fell into two classes of fractal-based point
      processes characterized by statistically self-similar behavior reflecting long
      range correlations among data points. Classification of a time series as either a
      fractional Gaussian noise (fGn)-or fractional Brownian motion (fBm)-based point
      process depended on the scaling exponent, alpha, of the power law in the Allan
      factor curve. fGn is defined as 0 < alpha < 1 and fBm as 1 < alpha < 3. The
      process responsible for the fractal spike trains of 11 of 12 classifiable LTF
      neurons with sympathetic nerve-related activity was fGn. In contrast, the process
      responsible for the fractal spike trains of eight of nine classifiable RVLM
      presympathetic neurons was fBm. The time series of simultaneously recorded
      vertebral sympathetic nerve discharge and the arterial pulse also were fBm-based
      signals. Because a fBm signal is the cumulative sum of the elements comprising
      the corresponding fGn signal, these results show smoothing of fractal time series
      in a feedforward direction from medullary presympathetic neurons to
      postganglionic sympathetic neurons. This may involve integration by RVLM neurons
      of their LTF inputs or independent fractal processes acting at different levels
      of the network controlling sympathetic nerve discharge. Whether feedforward
      smoothing of fractal signals is a feature in other neural systems is open to
      investigation.

PMID- 16306173
TI  - Mu opioid receptor activation inhibits GABAergic inputs to basolateral amygdala
      neurons through Kv1.1/1.2 channels.
AB  - The basolateral amygdala (BLA) is the major amygdaloid nucleus distributed with
      mu opioid receptors. The afferent input from the BLA to the central nucleus of
      the amygdala (CeA) is considered important for opioid analgesia. However, little
      is known about the effect of mu opioids on synaptic transmission in the BLA. In
      this study, we examined the effect of mu opioid receptor stimulation on the
      inhibitory and excitatory synaptic inputs to CeA-projecting BLA neurons. BLA
      neurons were retrogradely labeled with a fluorescent tracer injected into the CeA
      of rats. Whole cell voltage-clamp recordings were performed on labeled BLA
      neurons in brain slices. The specific mu opioid receptor agonist, (D-Ala2,N-Me
      Phe4,Gly5-ol)-enkephalin (DAMGO, 1 microM), significantly reduced the frequency
      of miniature inhibitory postsynaptic currents (mIPSCs) in 77% of cells tested.
      DAMGO also significantly decreased the peak amplitude of evoked IPSCs in 75% of
      cells examined. However, DAMGO did not significantly alter the frequency of
      mEPSCs or the peak amplitude of evoked EPSCs in 90% and 75% of labeled cells,
      respectively. Bath application of the Kv channel blockers, 4-AP (Kv1.1, 1.2, 1.3,
      1.5, 1.6, 3.1, 3.2), alpha-dendrotoxin (Kv1.1, 1.2, 1.6), dendrotoxin-K (Kv1.1),
      or tityustoxin-Kalpha (Kv1.2) each blocked the inhibitory effect of DAMGO on
      mIPSCs. Double immunofluorescence labeling showed that some of the
      immunoreactivities of Kv1.1 and Kv1.2 were colocalized with synaptophysin in the
      BLA. This study provides new information that activation of presynaptic mu opioid
      receptors primarily attenuates GABAergic synaptic inputs to CeA-projecting
      neurons in the BLA through a signaling mechanism involving Kv1.1 and Kv1.2
      channels.

PMID- 16306174
TI  - Lack of the Kir4.1 channel subunit abolishes K+ buffering properties of
      astrocytes in the ventral respiratory group: impact on extracellular K+
      regulation.
AB  - Ongoing rhythmic neuronal activity in the ventral respiratory group (VRG) of the
      brain stem results in periodic changes of extracellular K+. To estimate the
      involvement of the weakly inwardly rectifying K+ channel Kir4.1 (KCNJ10) in
      extracellular K+ clearance, we examined its functional expression in astrocytes
      of the respiratory network. Kir4.1 was expressed in astroglial cells of the VRG,
      predominantly in fine astrocytic processes surrounding capillaries and in close
      proximity to VRG neurons. Kir4.1 expression was up-regulated during early
      postnatal development. The physiological role of astrocytic Kir4.1 was studied
      using mice with a null mutation in the Kir4.1 channel gene that were interbred
      with transgenic mice expressing the enhanced green fluorescent protein in their
      astrocytes. The membrane potential was depolarized in astrocytes of Kir4.1-/-
      mice, and Ba2+-sensitive inward K+ currents were diminished. Brain slices from
      Kir4.1-/- mice, containing the pre-Botzinger complex, which generates a
      respiratory rhythm, did not show any obvious differences in rhythmic bursting
      activity compared with wild-type controls, indicating that the lack of Kir4.1
      channels alone does not impair respiratory network activity. Extracellular K+
      measurements revealed that Kir4.1 channels contribute to extracellular K+
      regulation. Kir4.1 channels reduce baseline K+ levels, and they compensate for
      the K+ undershoot. Our data indicate that Kir4.1 channels 1) are expressed in
      perineuronal processes of astrocytes, 2) constitute the major part of the
      astrocytic Kir conductance, and 3) contribute to regulation of extracellular K+
      in the respiratory network.

PMID- 16306175
TI  - Tonic and phasic respiratory drives to human genioglossus motoneurons during
      breathing.
AB  - A tongue muscle, the genioglossus (GG), is important in maintaining pharyngeal
      airway patency. Previous recordings of multiunit electromyogram (EMG) suggest it
      is activated during inspiration in humans with some tonic activity in expiration.
      We recorded from populations of single motor units in GG in seven subjects during
      quiet breathing when awake. Ultrasonography assisted electrode placement. The
      activity of single units was separated into six classes based on a step-wise
      analysis of the discharge pattern. Phasic and tonic activities were analyzed
      statistically with the coefficient of determination (r2) between discharge
      frequency and lung volume. Of the 110 motor units, 29% discharged tonically
      without phasic respiratory modulation (firing rate approximately 19 Hz). Further,
      16% of units increased their discharge during expiration (expiratory phasic and
      expiratory tonic units). Only half the units increased their discharge during
      inspiration (inspiratory phasic and inspiratory tonic units). Units firing
      tonically with an inspiratory increase had significantly higher discharge rates
      than those units that only fired phasically (peak rates 25 vs. 16 Hz,
      respectively). Simultaneous recordings of two or three motor units showed
      neighboring units with differing respiratory and tonic drives. Our results
      provide a classification and the first quantitative measures of human GG motor
      unit behavior and suggest this activity results from a complex interaction of
      inspiratory, expiratory, and tonic drives at the hypoglossal motor nucleus. The
      presence of different drives to GG implies that complex premotor networks can
      differentially engage human hypoglossal motoneurons during respiration. This is
      unlike the ordered recruitment of motor units in limb and axial muscles.

PMID- 16306176
TI  - Functional organization of ganglion cells in the salamander retina.
AB  - Recently, we reported a novel technique for recording all of the ganglion cells
      in a retinal patch and showed that their receptive fields cover visual space
      roughly 60 times over in the tiger salamander. Here, we carry this analysis
      further and divide the population of ganglion cells into functional classes using
      quantitative clustering algorithms that combine several response characteristics.
      Using only the receptive field to classify ganglion cells revealed six cell
      types, in agreement with anatomical studies. Adding other response measures
      served to blur the distinctions between these cell types rather than resolve
      further classes. Only the biphasic off type had receptive fields that tiled the
      retina. Even when we attempted to split these classes more finely, ganglion cells
      with almost identical functional properties were found to have strongly
      overlapping spatial receptive fields. A territorial spatial organization, where
      ganglion cell receptive fields tend to avoid those of other cells of the same
      type, was only found for the biphasic off cell. We further studied the functional
      segregation of the ganglion cell population by computing the amount of visual
      information shared between pairs of cells under natural movie stimulation. This
      analysis revealed an extensive mixing of visual information among cells of
      different functional type. Together, our results indicate that the salamander
      retina uses a population code in which every point in visual space is represented
      by multiple neurons with subtly different visual sensitivities.

PMID- 16306177
TI  - Direction selectivity of neurons in the striate cortex increases as stimulus
      contrast is decreased.
AB  - Various properties of external scenes are integrated during the transmission of
      information along central visual pathways. One basic property concerns the
      sensitivity to direction of a moving stimulus. This direction selectivity (DS) is
      a fundamental response characteristic of neurons in the visual cortex. We have
      conducted a neurophysiological study of cells in the visual cortex to determine
      how DS is affected by changes in stimulus contrast. Previous work shows that a
      neuron integration time is increased at low contrasts, causing temporal changes
      of response properties. This leads to the prediction that DS should change with
      stimulus contrast. However, the change could be in a counterintuitive direction,
      i.e., DS could increase with reduced contrast. This possibility is of intrinsic
      interest but it is also of potential relevance to recent behavioral work in which
      human subjects exhibit increased DS as contrast is reduced. Our
      neurophysiological results are consistent with this finding, i.e., the degree of
      DS of cortical neurons is inversely related to stimulus contrast. Temporal phase
      differences of inputs to cortical cells may account for this result.

PMID- 16306179
TI  - Background activity regulates excitability of rat hippocampal CA1 pyramidal
      neurons by adaptation of a K+ conductance.
AB  - In the in vivo brain background synaptic activity has a strong modulatory
      influence on neuronal excitability. Here we report that in rat hippocampal
      slices, blockade of endogenous in vitro background activity results in an
      increased excitability of CA1 pyramidal neurons within tens of minutes. The
      increase in excitability constitutes a leftward shift in the input-output
      relationship of pyramidal neurons, indicating a reduced threshold for the
      induction of action potentials. The increase in excitability results from an
      adaptive decrease in a sustained K+ conductance, as recorded from somatic cell
      attached patches. After 20 min of blockade of background activity, the mean
      sustained K+ current amplitude in somatic patches was reduced to 46 +/- 9% of
      that in time-matched control patches. Blockade of background activity did not
      affect fast Na+ conductance. Together, these results suggests that the reduction
      in K+ conductance serves as an adaptive mechanism to increase the excitability of
      CA1 pyramidal neurons in response to changes in background activity such that the
      dynamic range of the input-output relationship is effectively maintained.

PMID- 16306178
TI  - Effects of oleic acid on distinct populations of neurons in the hypothalamic
      arcuate nucleus are dependent on extracellular glucose levels.
AB  - Pharmacological manipulation of fatty acid metabolism in the hypothalamic arcuate
      nucleus (ARC) alters energy balance and glucose homeostasis. Thus, we tested the
      hypotheses that distinctive populations of ARC neurons are oleic acid (OA)
      sensors that exhibit a glucose dependency, independent of whether some of these
      OA sensors are also glucose-sensing neurons. We used patch-clamp recordings to
      investigate the effects of OA on ARC neurons in brain slices from 14- to 21-day
      old Sprague-Dawley (SD) rats. Additionally, we recorded spontaneous discharge
      rate in ARC neurons in 8-wk-old fed and fasted SD rats in vivo. Patch-clamp
      studies showed that in 2.5 mM glucose 12 of 94 (13%) ARC neurons were excited by
      2 microM OA (OA-excited or OAE neurons), whereas six of 94 (6%) were inhibited
      (OA-inhibited2.5 or OAI2.5 neurons). In contrast, in 0.1 mM glucose, OA inhibited
      six of 20 (30%) ARC neurons (OAI0.1 neurons); none was excited. None of the
      OAI0.1 neurons responded to OA in 2.5 mM glucose. Thus OAI2.5 and OAI0.1 neurons
      are distinct. Similarly, in seven of 20 fed rats (35%) the overall response was
      OAE-like, whereas in three of 20 (15%) it was OAI-like. In contrast, in fasted
      rats only OAI-like response were observed (three of 15; 20%). There was minimal
      overlap between OA-sensing neurons and glucose-sensing neurons. In conclusion, OA
      regulated three distinct subpopulations of ARC neurons in a glucose-dependent
      fashion. These data suggest that an interaction between glucose and fatty acids
      regulates OA sensing in ARC neurons.

PMID- 16306180
TI  - Differences in arithmetic subtraction of nonsymbolic numerosities by deaf and
      hearing adults.
AB  - Previous research has demonstrated that both hearing adults and hearing children
      with no training in arithmetic successfully performed approximate arithmetic on
      large sets of elements. Here, the possibility is explored that the same
      phenomenon can be confirmed in deaf adults who have acquired a signed language as
      their first language. Results reveal that they can perform simple arithmetic
      subtraction on nonsymbolic numerosities. Their performance levels were even
      higher than those of hearing adults who participated in the experiment as a
      control group. On the other hand, the performance levels of subtraction of the
      deaf adults in the formal mathematics were lower than those of the hearing
      adults. The findings are argued in terms of the characteristics of cognitive
      capabilities the deaf adults acquired through their development.

PMID- 16306181
TI  - The role of obstetric events in schizophrenia.

PMID- 16306183
TI  - Adeno-associated virus-based gene therapy for inherited disorders.
AB  - Adeno-associated virus vectors are capable of long-term gene transfer without
      obvious adverse effects in a number of animal models. Over the last two decades,
      preclinical and early phase clinical trials in cystic fibrosis and alpha-1
      antitrypsin deficiency were undertaken to test the feasibility of this approach.
      The results of those studies have been important since they have indicated that
      in vivo gene transfer is feasible and relatively safe. In addition, a number of
      key limitations to the current generation of AAV2 gene therapy vectors have been
      defined. The information about these limitations has been used to develop newer
      AAV vector approaches, based on new mutant and alternative serotype capsids and
      enhanced promoter systems. The evaluation of safety and efficacy of these newer
      agents is ongoing.

PMID- 16306184
TI  - Brain imaging in FAS: commentary on the article by Malisza et al.

PMID- 16306185
TI  - Evaluation of spatial working memory function in children and adults with fetal
      alcohol spectrum disorders: a functional magnetic resonance imaging study.
AB  - Magnetic resonance imaging (MRI) and functional MRI studies involving n-back
      spatial working memory (WM) tasks were conducted in adults and children with
      Fetal Alcohol Spectrum Disorders (FASD), and in age- and sex-matched controls.
      FMRI experiments demonstrated consistent activations in regions of the brain
      associated with working memory. Children with FASD displayed greater inferior
      middle frontal lobe activity, while greater superior frontal and parietal lobe
      activity was observed in controls. Control children also showed an overall
      increase in frontal lobe activity with increasing task difficulty, while children
      with FASD showed decreased activity. FASD adults demonstrated less functional
      brain activity overall, but greater inferior-middle frontal lobe activity during
      the simpler tasks, relative to controls. Control adults demonstrated greater
      inferior frontal activity with increasing task difficulty, while this pattern was
      not consistently observed in FASD adults. All four groups showed increasing
      activity with increases in task difficulty in the parietal and frontal regions at
      more superior slice levels. The results suggest impairment in spatial working
      memory in those with FASD that does not improve with age, and that fMRI may be
      useful in evaluation of brain function in these individuals.

PMID- 16306186
TI  - A Guinea pig model for the identification of in utero alcohol exposure using
      fatty acid ethyl esters in neonatal hair.
AB  - Measuring levels of fatty acid ethyl esters (FAEE) in hair has been a useful way
      to discriminate between adult heavy and nondrinkers. Extending the use of FAEE
      into neonatal hair to objectively identify children exposed to alcohol in utero
      may revolutionize current methods used to diagnose fetal alcohol spectrum
      disorder (FASD). Here we confirm for the first time that chronic exposure to
      alcohol during pregnancy in guinea pigs leads to increased levels of FAEE in both
      maternal and neonatal hair. The mean cumulative FAEE concentration in exposed
      maternal samples taken at GD57 was 0.431+/-0.140 pmol/mg (mean+/-SEM); levels
      observed in corresponding sucrose and water controls were 10-fold lower.
      Similarly, FAEE concentrations in exposed offspring samples taken at postnatal d
      1 (mean cumulative FAEE=0.491+/-0.177 pmol/mg) were more than 15-fold higher than
      control counterparts. Sixty percent of all alcohol-exposed animal samples
      contained two or more quantifiable FAEE, whereas close to 90% of either water or
      sucrose control samples did not have more than one quantifiable level of a single
      FAEE. Results of this study suggest that FAEE in neonatal hair may be useful
      biomarkers in identifying in utero alcohol exposure and may facilitate the early
      diagnosis and treatment of FASD.

PMID- 16306187
TI  - Brainstem auditory function at term in preterm babies with and without perinatal
      complications.
AB  - Functional integrity of the auditory brainstem was studied at term in babies born
      at 30-36 wk of gestation using maximum length sequence brainstem auditory evoked
      response (MLS BAER). Compared with normal term babies, preterm babies who had
      perinatal complications showed a tendency of an increase in wave V latency and I
      V and III-V intervals at all 91-910/s clicks, with statistical significance at
      higher rates. Wave V latency and I-V interval increased significantly at 455/s
      and 910/s. III-V interval increased at all click rates, which was more
      significant at higher rates. III-V/I-III interval ratio increased at most rates.
      Waves III and V amplitudes reduced significantly mainly at 455/s and 910/s. In
      preterm babies who had no perinatal complications, there were no major MLS BAER
      abnormalities except an increase in III-V interval at 91-910/s. By comparison,
      the preterm babies with perinatal complications had a significant increase in
      wave V latency, I-V and III-V intervals, and III-V/I-III interval ratio at 455/s
      and 910/s clicks. These results suggest that although there are no major
      abnormalities in brainstem auditory function in preterm babies without perinatal
      complications, the auditory brainstem, mainly the more central part, in preterm
      babies with perinatal complications is impaired, which becomes more apparent at
      very high stimulus rates. We conclude that preterm babies with perinatal
      complications are at high risk of central auditory impairment.

PMID- 16306188
TI  - S100B protein in urine of preterm newborns with ominous outcome.
AB  - Prematurity is an important cause of perinatal death, and no reliable
      biochemical/biophysical markers exist to identify newborns with an increased
      mortality risk. We aimed to use S100B concentrations in urine as an early
      indicator of risk of neonatal death. We did a cross-sectional study using urine
      obtained from 165 preterm newborns, of whom 11 suffered neonatal death within the
      first week, 121 displayed no overt neurologic syndrome, and 33 suffered neonatal
      hypoxia and intraventricular hemorrhage (IVH) but not ominous outcome. Urine
      S100B concentrations were determined at four time-points and corrected for
      gestational age by conversion to multiples of median (MoM) of healthy controls of
      the same gestational age. Ultrasound imaging was assessed within the first 72 h
      from birth. In infants that died within the first week, S100B levels in urine
      were already higher than controls at first urination and increased progressively
      between the 24 and 96-h time-points. Multiple logistic regression analysis showed
      a significant correlation between urine S100B protein concentrations and the
      occurrence of neonatal death. An S100B concentration cut-off of 12.93 MoM at
      first urination had a sensitivity of 100% and a specificity of 97.8% for
      predicting an ominous outcome. The positive predictive value was 78.6%, the
      negative predictive value was 100%. Measurement of urine S100B protein levels in
      preterm newborns could be useful to identify newborns at higher risk of neonatal
      death.

PMID- 16306189
TI  - Evaluation of a model for brain bilirubin uptake in jaundiced newborns.
AB  - A model for brain bilirubin uptake (BBU) predicts that BBU in jaundiced newborns
      typically depends on the plasma total bilirubin concentration (TBC) and the
      bilirubin-albumin dissociation rate constant (k1) rather than the unbound
      bilirubin (Bf). The model's validity was tested by 1) evaluating its requirement
      that k3>>>k2, where k3 and k2 are the rate constants for BBU and Bf-albumin
      association, respectively, and 2) determining whether the calculated BBU is
      <or=5% of the bilirubin production rate, the approximate BBU expected if brain
      bilirubin levels are <1% of the miscible bilirubin pool as reported in the
      literature. The model was investigated using peroxidase test measurements of TBC,
      Bf, k1, and k2 from 185 jaundiced newborns. Mean k2 was compared with the
      reported k3 value of 0.08/s. BBU calculated from TBC and k1 was expected to be
      <or=0.005 microg/kg/s given the reported bilirubin production rate of 0.1
      microg/kg/s. BBU calculated using Bf was also compared with the bilirubin
      production rate. The mean k2 of 8.9 L/micromol/s was greater than k3, and the
      mean BBU of 0.72 microg/kg/s exceeded the expected range of <or=0.005
      microg/kg/s. However, mean BBU using Bf (0.00073 microg/kg/s) was within the
      expected range. A mathematical model calculating BBU as a function of TBC and k1
      could not be validated. BBU calculated from Bf is consistent with the observation
      that <1% of the miscible bilirubin pool is distributed in the brain.

PMID- 16306190
TI  - The effect of blue light exposure on the expression of circadian genes: bmal1 and
      cryptochrome 1 in peripheral blood mononuclear cells of jaundiced neonates.
AB  - The purpose of this study was to investigate the effect of blue light
      phototherapy on the expression of circadian genes in peripheral blood mononuclear
      cells (PBMC) and plasma melatonin levels in neonates. Real-time reverse
      transcriptase polymerase chain reaction (RT-PCR) was used to determine the
      expression of Bmal1 and Cry1 in PBMC, and an enzyme-linked immunosorbent assay
      was used to determine plasma melatonin levels in 32 breast-milk jaundiced
      neonates before and after phototherapy, compared with 29 control neonates. The
      results showed that the expression of Bmal1 was decreased and Cry1 increased
      significantly after phototherapy. Plasma melatonin levels were decreased after
      phototherapy. There was no statistical difference in Bmal1 and Cry1 gene
      expression and plasma melatonin levels in the control group. In conclusion,
      phototherapy does affect the expression of the circadian genes Bmal1 and Cry1 in
      PBMC and plasma melatonin concentration in jaundiced neonates. Our results
      suggest that phototherapy should be timed according to circadian rhythms when
      treating jaundiced neonates.

PMID- 16306191
TI  - Preinoculation with the probiotic Lactobacillus acidophilus early in life
      effectively inhibits murine Citrobacter rodentium colitis.
AB  - Enteropathogenic Escherichia coli (EPEC) is a common pathogen in infantile
      diarrhea, causing a characteristic histopathologic attaching and effacing (A/E)
      lesion in the intestinal mucosa. The mouse pathogen Citrobacter rodentium causes
      a similar A/E lesion in the murine intestine. Like EPEC, C. rodentium infection
      results in colonic crypt hyperplasia, goblet cell depletion, epithelial
      proliferation, and mucosal disruption. Using this murine model, we tested the
      hypothesis that preinoculation of murine gut with Lactobacillus acidophilus early
      in life can enhance host defense against enteric bacterial infection and
      attenuate bacteria-mediated colitis. Two-week old BALB/c mice were inoculated
      with L. acidophilus twice per week for 4 weeks before C. rodentium infection or
      concomitantly with the exposure to C. rodentium at 6-8 weeks of age. The
      probiotics were administered twice weekly thereafter. We observed that L.
      acidophilus inoculation in mice inhibits C. rodentium-induced colitis, which is
      associated with a decrease in C. rodentium colonization and translocation, an
      increase in its clearance, and a suppression of colonic myeloperoxidase (MPO)
      activity. Probiotic treatment also stimulates regulatory cytokine expression in
      the colon [transforming growth factor beta (TGF-beta), interleukin (IL)-10].
      Preinoculation with L. acidophilus is more effective than concomitant use of
      probiotics in the induction of intestinal IgA secretion and in the downregulation
      of proinflammatory cytokine expression [tumor necrosis factor alpha (TNF-alpha),
      IL-6, and IL-12]. These observations suggest that inoculation with probiotics can
      effectively prevent bacteria-induced colitis by limiting enteric bacteria
      infection and promoting mucosal protective regulatory immune responses. This
      study may have ramifications for prevention of infectious diarrhea in human
      infants and children, particularly in developing countries.

PMID- 16306193
TI  - Direct binding of respiratory syncytial virus to pneumococci: a phenomenon that
      enhances both pneumococcal adherence to human epithelial cells and pneumococcal
      invasiveness in a murine model.
AB  - In a previous study we showed that pneumococcal adherence to epithelial cells was
      enhanced by a preceding respiratory syncytial virus (RSV) infection. RSV
      glycoproteins, expressed on the infected cell surface, may play a role in this
      enhanced pneumococcal binding, by acting as bacterial receptors. In the current
      study, it was attempted to analyze the capacity of pneumococci to interact
      directly with RSV virions. By flow-cytometry, a direct interaction between RSV
      and pneumococci could be detected. Heparin, an inhibitor of RSV infectivity that
      interacts with RSV protein-G, blocked RSV-pneumococcal binding, indicating that
      the latter interaction is indeed mediated by protein-G. RSV-pneumococcal
      complexes showed enhanced adherence to uninfected human epithelial cells,
      compared with pneumococcal adherence without bound RSV, and this enhancement was
      also blocked by heparin. In addition, the significance of these findings in vitro
      was explored in vivo in a murine model. Both mice that were pretreated with RSV
      at day 4 before pneumococcal challenge and mice infected with both agents
      simultaneously showed significantly higher levels of bacteraemia than controls.
      Simultaneous infection with both agents enhanced the development of pneumococcal
      bacteraemia most strongly. It was hypothesized that direct viral binding is
      another mechanism by which RSV can induce enhanced pneumococcal binding to
      epithelial cells, a phenomenon that is translated in vivo by a higher
      invasiveness of pneumococci when administered simultaneously with RSV to mice.
      Apparently, RSV acts in this process as a direct coupling particle between
      bacteria and uninfected epithelial cells, thereby increasing colonization by and
      enhancing invasiveness of pneumococci.

PMID- 16306192
TI  - Signal transduction pathways involved in oxidative stress-induced intestinal
      epithelial cell apoptosis.
AB  - Necrotizing enterocolitis (NEC) is a devastating inflammatory condition of the
      gut that occurs in premature infants. Ischemia-reperfusion gut injury with
      production of reactive oxygen species (ROS) is thought to contribute to NEC; the
      exact cellular mechanisms involved are largely unknown. The purpose of this study
      was to determine the intracellular signaling transduction pathways involved in
      oxidative stress-induced intestinal epithelial cell apoptosis. H2O2 treatment
      resulted in rat intestinal epithelial cell apoptosis in a dose- and time
      dependent manner; the caspase inhibitor, zVAD-fmk, blocked this response. Western
      blotting was performed to determine phosphorylation of kinases and ELISA was used
      to assess DNA fragmentation, as a measure of apoptosis. A rapid increase in
      phosphorylation of extracellular signal-related kinase (ERK)1/2, c-Jun N-terminal
      kinase (JNK)1/2, and Akt was noted. Inhibition of ERK and JNK decreased H2O2
      induced apoptosis. Additionally, inhibition of protein kinase C (PKC) and
      phosphatidylinositol 3-kinase (PI3-K) attenuated and enhanced H2O2-mediated
      apoptosis and mitochondrial membrane potential decrease, respectively.
      Furthermore, activation of PKC reduced the Akt phosphorylation, whereas
      inhibition of PKC attenuated H2O2-mediated activation of caspase-3 and enhanced
      the H2O2-induced Akt phosphorylation. This study shows that activation of
      multiple signaling transduction pathways occurs during oxidative stress-induced
      intestinal epithelial cell injury. In contrast to ERK, JNK, and PKC, PI3-K/Akt
      may play an important role as a protective cellular signaling pathway during this
      process.

PMID- 16306194
TI  - Pulmonary and systemic induction of SAA3 after ventilation and endotoxin in
      preterm lambs.
AB  - Serum amyloid A (SAA), an acute phase reactant (APR) protein, is induced in liver
      during systemic inflammation. Serum amyloid A3 (SAA3), an isoform of SAA, is
      induced in both liver and extra hepatic sites in response to proinflammatory
      stimuli such as cytokines. Previously, we showed a modest increase in plasma
      cytokine levels in a preterm lamb model of lung injury. The study objective was
      to determine the relative contributions of lung and liver to the acute phase
      response during postnatal lung injury. Preterm (130d) and near term (141d)
      newborn lambs (term=150d) were randomized to either no ventilation (controls),
      ventilation+intratracheal (IT) endotoxin (endo) or ventilation+IT saline. A group
      of near term lambs were exposed to ventilation+IV endotoxin. In the lungs,
      ventilation alone increased SAA3 mRNA 3- and 13-fold while ventilation+IT
      endotoxin increased SAA3 mRNA 64 and 366-fold above controls in preterm and near
      term lambs, respectively. In the liver, SAA3 mRNA was induced by ventilation
      alone (three-fold) and ventilation+IT endotoxin (45-fold) above controls in both
      preterm and near term animals. Ventilation + IV endotoxin caused the highest
      increase in SAA3 mRNA (212-fold) in the liver of near term animals. A different
      isoform, identified as SAA-Liver inducible was maximally induced in liver by
      ventilation alone with minimal further response to endotoxin. Lung SAA3 mRNA
      expression was detected primarily in airway epithelium, bronchial glands,
      perichondrium of bronchial cartilage and vascular smooth muscle cells. Our
      experiments show rapid induction of an APR gene in lung in response to
      proinflammatory stimuli.

PMID- 16306195
TI  - Partitioning of airway and parenchymal mechanics in unsedated newborn infants.
AB  - The recent trend toward development of noninvasive methods that can accurately
      evaluate the lung periphery has particular relevance for the predominantly
      parenchymal nature of neonatal respiratory disease. Concerns regarding the safety
      of sedating newborn (especially preterm) infants have also stimulated a drive
      toward measurements obtained during natural sleep. This study aimed to adapt
      existing methodology for the low-frequency forced oscillation technique to obtain
      partitioned measurements of airway and parenchymal mechanics during unsedated,
      quiet sleep in newborn infants without a history of previous respiratory disease.
      A face mask was positioned over the infant's mouth and nose and a brief (4-5 s)
      breathing pause was induced by evoking the Hering-Breuer reflex via end
      inspiratory occlusion at raised lung volume (airway opening occluded at 2 kPa).
      Airway opening pressure and flow were measured while a pseudorandom noise (2-14
      Hz) was applied to the airway. Acceptable pulmonary impedance data were collected
      in 11 of the 12 infants studied (34.1-42.6 wk postmenstrual age, 1.9-3.9 kg body
      weight) on 17 (total of 20) occasions. Airway parameters (resistance and
      inertance) and respiratory tissue parameters were calculated from the resultant
      impedance spectra. Tissue resistance and tissue elastance decreased with
      increasing body length albeit at different rates such that hysteresivity (tissue
      resistance/tissue elastance) also decreased. There was a trend toward reduction
      in airway resistance with increasing length. Measurements of lung function are
      feasible in the unsedated newborn infant using low-frequency forced oscillations
      and confirm the important contribution of tissue resistance to lung mechanics in
      the developing lung.

PMID- 16306196
TI  - Combined treatment with a nonselective nitric oxide synthase inhibitor (l-NMMA)
      and indomethacin increases ductus constriction in extremely premature newborns.
AB  - Studies in premature animals suggest that 1) prolonged tight constriction of the
      ductus arteriosus is necessary for permanent anatomic closure and 2) endogenous
      nitric oxide (NO) and prostaglandins both play a role in ductus patency. We
      hypothesized that combination therapy with an NO synthase (NOS) inhibitor [N(G)
      monomethyl-L-arginine (L-NMMA)] and indomethacin would produce tighter ductus
      constriction than indomethacin alone. Therefore, we conducted a phase I and II
      study of combined treatment with indomethacin and L-NMMA in newborns born at <28
      weeks' gestation who had persistent ductus flow by Doppler after an initial three
      dose prophylactic indomethacin course (0.2, 0.1, 0.1 mg/kg/24 h). Twelve infants
      were treated with the combined treatment protocol [three additional indomethacin
      doses (0.1 mg/kg/24 h) plus a 72-hour L-NMMA infusion]. Thirty-eight newborns
      received three additional indomethacin doses (without L-NMMA) and served as a
      comparison group. Ninety-two percent (11/12) of the combined treatment group had
      tight ductus constriction with elimination of Doppler flow. In contrast, only 42%
      (16/38) of the comparison group had a similar degree of constriction. L-NMMA
      infusions were limited in dose and duration by acute side effects. Doses of 10-20
      mg/kg/h increased serum creatinine and systemic blood pressure. At 5 mg/kg/h,
      serum creatinine was stable but systemic hypertension still limited L-NMMA dose.
      We conclude that combined inhibition of NO and prostaglandin synthesis increased
      the degree of ductus constriction in newborns born at <28 weeks' gestation.
      However, the combined administration of L-NMMA and indomethacin was limited by
      acute side effects in this treatment protocol.

PMID- 16306197
TI  - Increased NCAM expression and vascular development in trisomy 16 mouse embryos:
      relationship with nuchal translucency.
AB  - Increased nuchal translucency in the human fetus is associated with chromosomal
      abnormalities, enlarged jugular lymphatic sacs, cardiac defects and changed flow
      through the ductus venosus. The developmental background of this nuchal edema in
      relation to the associated anomalies remains elusive. We studied the morphologic
      correlation between neurogenesis and vasculogenesis in neck, heart, and ductus
      venosus region of wild type and trisomy 16 mice embryos (E10- E18), using an
      antibody against Neural Cell Adhesion Molecule (NCAM). Trisomy 16 mice are a
      model for the above described human phenotype. From E12 trisomy 16 mice showed an
      altered arrangement of cranial nerves IX, X and XI, which are positioned between
      the carotid artery, jugular vein and enlarged lymphatic sac. The vagal nerve was
      significantly smaller, compared with wild type embryos. NCAM was over expressed
      in both neuronal and cardiovascular structures in trisomy 16 mice, being
      particularly prominent in the 4th and 6th pharyngeal arch arteries, and the
      ductus venosus. In the 4th and 6th pharyngeal arch arteries, NCAM over expression
      was located to the part of the vessel wall that is closely related to the vagal
      and recurrent nerve. In case of 4th pharyngeal arch artery abnormalities NCAM
      expression, on the other hand, was reduced. In conclusion, the interaction
      between neurogenesis and vasculogenesis is disturbed in the trisomy 16 mouse
      model, and might be a common denominator in the spectrum of anomalies associated
      with increased nuchal translucency.

PMID- 16306198
TI  - Placental expression of angiopoietin-1, angiopoietin-2 and tie-2 during placental
      development in an ovine model of placental insufficiency-fetal growth
      restriction.
AB  - Fetal growth restriction (FGR) is associated with increased perinatal morbidity
      and mortality, and often results from functional placental insufficiency.
      Placentation requires extensive vasculogenesis and subsequent angiogenesis, in
      both maternal and fetal tissues. Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang
      2) are angiogenic growth factors expressed in the placenta, and compete for
      binding to a common receptor, Tunica interna endothelial cell kinase-2 (Tie-2).
      Our objective was to examine Ang-1, Ang-2 and Tie-2 expression in ovine placental
      tissue obtained from normal and FGR pregnancies throughout gestation. Fetal
      cotyledon and maternal caruncle tissue concentrations of Ang-1, Ang-2 and Tie-2
      mRNA were assessed by real-time reverse transcriptase-polymerase chain reaction
      and protein concentrations were assessed by Western immunoblot analysis, at 55,
      90 and 135 d gestational age (dGA). Concentrations of Ang-1, Ang-2 and Tie-2 mRNA
      in FGR fetal cotyledons were increased at 55 dGA, and Tie-2 mRNA concentrations
      were decreased in FGR fetal cotyledons and maternal caruncles at 135 dGA.
      Immunoblot analysis demonstrated increased concentrations of Ang-2 in the fetal
      cotyledon at 55 dGA, and lower concentrations at 135 dGA. In contrast,
      concentrations of Tie-2 were increased at 90 dGA, but tended to decrease at 135
      dGA in FGR maternal caruncles. The changes observed during early- to mid
      gestation may result in increased branching angiogenesis, but may also set the
      stage for increased nonbranching angiogenesis during late gestation, altered
      placental architecture and placental insufficiency that result in FGR.

PMID- 16306199
TI  - Glucocorticoid exposure in preterm babies predicts saliva cortisol response to
      immunization at 4 months.
AB  - Preterm babies are exposed to multiple stressors and this may have long-term
      effects. In particular, high levels of endogenous cortisol might have a
      programming effect on the hypothalamic-pituitary-adrenal axis as may administered
      glucocorticoids. In this study, we aimed to test the hypothesis that the level of
      endogenous and exogenous glucocorticoid exposure during the neonatal period
      predicts the saliva cortisol response to immunization at 4 mo of age. We followed
      45 babies born below 32 wk gestation. We showed that their concentration of
      plasma cortisol during the first 4 wk was 358, 314, 231, and 195 nmol/L cortisol,
      respectively (geometric mean). This is four to seven times higher than fetal
      levels at the same gestational age range. We used routine immunization at 4 mo
      and 12 mo as a stressor and measured the change in saliva cortisol as the stress
      response. Mean circulating cortisol in the first 4 wk predicted the cortisol
      response at 4 but not at 12 mo. Path analysis showed that birthweight for
      gestational age, therapeutic antenatal steroids, and therapeutic postnatal
      steroids also contributed to the magnitude of the saliva cortisol response at 4
      mo. This provides evidence that the magnitude of glucocorticoid exposure, both
      endogenous and exogenous, may have an effect on later stress responses.

PMID- 16306200
TI  - Sex differences in the relationships among weight gain, subcutaneous skinfold
      tissue and saltatory length growth spurts in infancy.
AB  - As the mechanisms controlling the amount and timing of growth saltations are not
      well understood, the identification of physiologic coupling in weight and length
      growth are important for further understanding normal growth biology. Thirty-four
      healthy infants (13 males, 21 females) participated in a longitudinal growth
      study during the first year. Weekly weights and s.c. skinfolds (limb and trunk)
      were analyzed in a growth event-focused study. Coincident analysis tested the
      null hypothesis of chance concurrence between significant weight gain and
      saltatory length growth spurts. Logistic regression quantified this relationship
      and investigated the interaction between incremental weight gain and s.c.
      skinfolds on length growth spurts. The null hypothesis of random coincidence
      between weight gain and saltatory length growth was not supported. For girls,
      significant weight gain and length growth were coupled during the same week and
      length saltations were 42% more likely during the weeks of significant weight
      gain, with no interaction from s.c. skinfolds. For boys, length growth saltations
      were coupled to both previous and concomitant weight gain but were predicted only
      by previous weight gain, controlling for confounders. Boys were 68% more likely
      to grow in length the week following significant weight gain, and initial
      abdominal to suprailiac skinfold ratios conferred a 4-fold increased likelihood
      of length growth within the week, controlling for confounders. These data
      generate the hypothesis that a common growth signal cascade couples growth in
      weight and length/height with a time delay due to sex-specific biology, reflected
      in a s.c. fat fold interface.

PMID- 16306201
TI  - Quantitative genetic analysis of the metabolic syndrome in Hispanic children.
AB  - Childhood obesity is associated with a constellation of metabolic derangements
      including glucose intolerance, hypertension, and dyslipidemia, referred to as
      metabolic syndrome. The purpose of this study was to investigate genetic and
      environmental factors contributing to the metabolic syndrome in Hispanic
      children. Metabolic syndrome, defined as having three or more metabolic risk
      components, was determined in 1030 Hispanic children, ages 4-19 y, from 319
      families enrolled in the VIVA LA FAMILIA study. Anthropometry, body composition
      by dual energy x-ray absorptiometry, clinical signs, and serum biochemistries
      were measured using standard techniques. Risk factor analysis and quantitative
      genetic analysis were performed. Of the overweight children, 20%, or 28% if
      abnormal liver function is included in the definition, presented with the
      metabolic syndrome. Odds ratios for the metabolic syndrome were significantly
      increased by body mass index z-score and fasting serum insulin; independent
      effects of sex, age, puberty, and body composition were not seen. Heritabilities
      +/- SE for waist circumference, triglycerides (TG), HDL, systolic blood pressure
      (SBP), glucose, and alanine aminotransferase (ALT) were highly significant.
      Pleiotropy (a common set of genes affecting two traits) detected between SBP and
      waist circumference, SBP and glucose, HDL and waist circumference, ALT and waist
      circumference, and TG and ALT may underlie the clustering of the components of
      the metabolic syndrome. Significant heritabilities and pleiotropy seen for the
      components of the metabolic syndrome indicate a strong genetic contribution to
      the metabolic syndrome in overweight Hispanic children.

PMID- 16306202
TI  - Effect of the cholesteryl ester transfer protein genotypes on plasma lipid and
      lipoprotein levels in Vietnamese children.
AB  - Cholesteryl ester transfer protein (CETP) is understood to play a regulatory role
      in HDL cholesterol (HDLC) metabolism. In this study, the effect of CETP genotypes
      on plasma lipid and lipoprotein levels in 348 Vietnamese girls (aged 7-9) with
      different nutritional conditions was analyzed. The two mutations, intron 14 G(+1)
      to-A (I14A) and Asp 442 to Gly within exon 15 (D442G), and the TaqIB polymorphism
      in the CETP gene were identified by an Invader assay. The D442G mutation was
      present with a frequency of 0.034, while the I14A mutation was absent. HDLC
      levels were significantly higher in carriers of the D442G mutation than in
      noncarriers, regardless of the nutritional status. Low-density lipoprotein (LDL)
      cholesterol and triglyceride levels were not significantly lower in carriers of
      D442G mutation. The frequency of the TaqIB2 allele was 0.34, which was lower than
      that observed in other Asian populations. TaqIB2B2 carriers also had
      significantly higher HDLC levels, but this association was weaker than that of
      the D442G mutation. Overall, genetic variations at the CETP gene locus may
      account for a significant proportion of HDLC variation in Vietnamese children.

PMID- 16306203
TI  - Maternal and cord blood long-chain polyunsaturated fatty acids are predictive of
      bone mass at birth in healthy term-born infants.
AB  - Long-chain polyunsaturated fatty acids (LC PUFA) are associated with bone mass in
      animals and human adults, yet no data exist for human infants. Thus, the
      objective of this study was to establish that LC PUFA status is associated with
      bone mass in healthy infants. Thirty mother-infant pairs were studied for LC PUFA
      status by measuring maternal and cord blood red blood cells (RBC) for arachidonic
      acid (AA), eicosapentaenoic acid (EPA), and DHA. Infant anthropometry and lumbar
      spine 1-4, femur and whole-body bone mineral content (BMC) were measured within
      15 d of delivery. Maternal and infant LC PUFA were tested for their relationship
      to BMC using Pearson correlation and backward step-wise regression analyses. At
      birth, the average gestational age was 39.3+/-1.1 wk and body weight was 3433+/
      430 g. Cord RBC AA was positively correlated with whole-body BMC, AA:EPA
      positively correlated with lumbar spine 1-4 BMC and femur BMC. Maternal RBC AA
      was positively correlated with whole-body BMC. After accounting for infant weight
      using regression, whole-body BMC was positively predicted by cord RBC AA but none
      of the maternal LC PUFA; lumbar spine 1-4 BMC was positively predicted by cord
      RBCAA:EPA ratio but negatively by maternal DHA; and femur BMC was not predicted
      by cord LC PUFA but was negatively predicted by maternal DHA. Imbalances among
      the n-6 and n-3 LC PUFA by term gestation are associated with lower bone mass,
      suggesting that the maternal diet should be balanced in n-6 and n-3 LC PUFA.

PMID- 16306204
TI  - Amino acids, glutamine, and protein metabolism in very low birth weight infants.
AB  - Glutamine has been proposed to be conditionally essential for premature infants,
      and the currently used parenteral nutrient mixtures do not contain glutamine. De
      novo glutamine synthesis (DGln) is linked to inflow of carbon into and out of the
      tricarboxylic acid (TCA) cycle. We hypothesized that a higher supply of
      parenteral amino acids by increasing the influx of amino acid carbon into the TCA
      cycle will enhance the rate of DGln. Very low birth weight infants were
      randomized to receive parenteral amino acids either 1.5 g/kg/d for 20 h followed
      by 3.0 g/kg/d for 5 h (AA1.5) or 3.0 g/kg/d for 20 h followed by 1.5 g/kg/d for 5
      h (AA3.0). A third group of babies received amino acids 1.5 g/kg/d for 20 h
      followed by 3.0 g/kg/d for 20 h (AA-Ext). Glutamine and protein/nitrogen kinetics
      were examined using [5-(15)N]glutamine, [2H5]phenylalanine, [1-(13)C,15N]leucine,
      and [15N2]urea tracers. An acute increase in parenteral amino acid infusion for 5
      h (AA1.5) resulted in decrease in rate of appearance (Ra) of phenylalanine and
      urea, but had no effect on glutamine Ra. Infusion of amino acids at 3.0 g/kg/d
      for 20 h resulted in increase in DGln, leucine transamination, and urea
      synthesis, but had no effect on Ra phenylalanine (AA-Ext). These data show an
      acute increase in parenteral amino acid-suppressed proteolysis, however, such an
      effect was not seen when amino acids were infused for 20 h and resulted in an
      increase in glutamine synthesis.

PMID- 16306205
TI  - Silver-Russell syndrome-like features in a patient carrying a novel NF1 mutation.
AB  - Mutations in the NF1 gene (17q11.2) cause neurofibromatosis type 1 (NF1), a
      pleiotropic and progressive autosomal dominant disorder with marked variability
      of clinical expression. Clinical diagnosis is usually readily achieved in most
      adult and adolescent patients due to the presence of at least two of the classic
      signs of NF1. However, the absence of many of the disease-defining features in
      young children frequently renders definite diagnosis impossible in this age
      group. Particularly, clinical diagnosis is challenging in young patients whose
      phenotypical presentation does not lie within the common spectrum of "typical"
      NF1 features. Sensitive and reliable molecular genetic testing can be of great
      help in these cases. Here, we report clinical and molecular findings in a 2-year
      old boy with features of NF1. Severe growth retardation together with other
      dysmorphic features was also suggestive for Silver-Russell syndrome (SRS) in this
      patient. Molecular genetic testing identified a novel NF1 mutation and, thus,
      enabled a confident NF1 diagnosis despite the unusual phenotypical presentation
      in this patient.

PMID- 16306206
TI  - Simultaneous mutations in the CLCNKB and SLC12A3 genes in two siblings with
      phenotypic heterogeneity in classic Bartter syndrome.
AB  - Two siblings (brother and sister) with renal tubular hypokalemic alkalosis
      underwent clinical, biochemical and molecular investigations. Although the
      biochemical findings were similar (including hypokalemia, metabolic alkalosis,
      hyperreninemia, hyperaldosteronism and normal blood pressure), the clinical
      findings were different: the boy, who also presented syndromic signs, developed
      glomerular proteinuria and renal biopsy revealed focal segmental glomerular
      sclerosis; the girl showed the typical signs of classic Bartter syndrome. As
      described in a previous paper, a heterozygous mutation (frameshift 2534delT) was
      demonstrated in the gene encoding the thiazide-sensitive NaCl co-transporter
      (SLC12A3) of the distal convoluted tubule; the second molecular analysis revealed
      a compound heterozygous mutation (A61D/V149E) in the CLCNKB chloride channel gene
      in both subjects, inherited in trans from the parents. The children were finally
      diagnosed as having classic Bartter syndrome. These cases represent the first
      report of the simultaneous presence of heterozygous and compound heterozygous
      mutations in the SLC12A3 and CLCNKB genes, both of which are involved in renal
      salt losing tubulopathies, and confirm previous observations regarding classic
      Bartter syndrome phenotype variability in the same kindred.

PMID- 16306207
TI  - Long-term effects of maternal diabetes on vascular reactivity and renal function
      in rat male offspring.
AB  - Fetal growth impairment can occur in pregnancy complicated by diabetes. Although
      several studies have focused the effects of nutritional status on intrauterine
      development, the long-term impact of maternal diabetes on vascular and renal
      function in the offspring is poorly investigated. In the present study, blood
      pressure profiles and renal function parameters were investigated in the
      offspring of diabetic rats (DO). Female rats were made diabetic throughout
      gestation with a single dose of streptozotocyn (STZ) 10 d before mating. After
      weaning, the offspring had free access to food and water. Arterial pressure was
      evaluated every 15 d. Functional and morphometric kidney studies were performed
      in newborn, 3, 6 and 12-mo-old male rats in DO and in controls, C. Although
      maternal diabetes did not affect nephron number in the young adult rat,
      glomerular hypertrophy developed from 3 mo on. Glomerular Filtration Rate and
      Renal Plasma Flow were observed to be significantly decreased in DO when compared
      with C, from 3 mo on. In DO, hypertension was observed from 8 wk on and persisted
      elevated throughout the experimental period (12 mo). Vascular reactivity,
      evaluated in mesenteric arterial bed showed a decreased endothelium-dependent
      vasodilatation in 12-mo-old DO animals, while preserved response to sodium
      nitroprusside was demonstrated. Our data show that exposure to intrauterine
      diabetes induced by STZ does not affect nephron number in the young offspring but
      can cause permanent changes in Nitric Oxide (NO)-related vascular response,
      which, in turn may accelerate the natural age-related nephron loss.

PMID- 16306208
TI  - Activating transcription factor 3 is up-regulated in patients with hypospadias.
AB  - Hypospadias is a congenital anomaly of the genitalia characterized by
      abnormalities of the urethra and foreskin, with the urethral meatus located in an
      abnormal position anywhere from the distal ventral penile shaft to the perineum.
      Because the incidence of hypospadias is approximately 1/200-1/300 live male
      births, it is one of the most common congenital malformations, but its etiology
      is largely uncharacterized. Genomic analysis of hypospadic tissue indicated a
      potential role for activating transcription factor 3 (ATF3) in the development of
      this anomaly. ATF3 may be involved in homeostasis, wound healing, cell adhesion,
      or apoptosis, and normally it is expressed at a steady-state in quiescent cells.
      Additionally, it has been shown to be an estrogen-responsive gene, and the
      etiology of hypospadias may be related to in utero exposure to estrogenic or anti
      androgenic compounds. We examined the expression of ATF3 in tissues from 28
      children with hypospadias compared with 20 normal penile skin tissue samples from
      elective circumcision. Eighty-six percent of the hypospadias samples were
      immunohistochemically positive, compared with 13% of normal tissue samples.
      Seventy-five percent of hypospadias samples were positive from in situ
      hybridization, compared with 1% of circumcision samples. Our results indicate
      that ATF3 is up-regulated in the penile skin tissues of boys with hypospadias,
      suggesting a role for this transcription factor in the development of this
      abnormality. Because the etiology of hypospadias may include exposure to
      estrogenic compounds, the responsiveness of ATF3 to estrogen is also discussed.

PMID- 16306209
TI  - Ontogeny of renal P-glycoprotein expression in mice: correlation with digoxin
      renal clearance.
AB  - Digoxin is eliminated mainly by the kidney through glomerular filtration and P
      glycoprotein (P-gp) mediated tubular secretion. Toddlers and young children
      require higher doses of digoxin per kilogram of bodyweight than adults, although
      the reasons for this have not been elucidated. We hypothesized there is an age
      dependant increase in P-gp expression in young children. The objectives of this
      study were to elucidate age-dependant expression of renal P-gp and its
      correlation with changes in the clearance rate of digoxin. FVB mice were killed
      at different ages to prepare total RNA for P-gp expression studies. Semi
      quantitative RT-PCR was conducted to analyze mdr1a and mdr1b ontogeny in the
      kidney at: birth, 7, 14, 21, 28 and 45-d old adults. The pharmacokinetics of
      digoxin (7 microg/kg) was studied in mice of the same age groups. Newborn and Day
      7 levels of both mdr1a and mdr1b were marginal. Day 21 mdr1b levels were
      significantly higher than both Day 14 and Day 28 levels. Digoxin clearance rates
      were the highest at Day 21, with significant correlation between P-gp expression
      and clearance values. Increases in digoxin clearance rates after weaning may be
      attributed, at least in part, to similar increases in P-gp expression.

PMID- 16306210
TI  - Neutrophil recruitment by fetal porcine endothelial cells: implications in
      scarless fetal wound healing.
AB  - Fetal dermal wounds heal scarlessly and with a minimal inflammatory response.
      When a robust inflammatory response is induced at the site of fetal dermal wounds
      by the application of cytokines, healing results in fibrosis. To test the
      hypothesis that the reduced inflammatory response in fetal wounds is due to
      impaired fetal leukocyte-endothelial interactions, the contributions of fetal
      endothelial cells to the inflammatory response in the fetus were investigated.
      Endothelial cells isolated from blood vessels of adult and mid-gestational fetal
      pigs were cultured in media until confluent monolayers were established. Adult
      porcine neutrophils were isolated and resuspended at a concentration of 1 million
      cells/mL. Interactions between neutrophils and endothelial cells were observed
      under static and flow conditions. Endothelial monolayers were exposed to
      neutrophils with and without prior stimulation of the endothelial cells with
      tumor necrosis factor alpha (TNF-alpha) for 4 h. The neutrophil-endothelial
      interactions were observed and analyzed for neutrophil adhesion, rolling
      velocity, and transmigration. Endothelial P-selectin mRNA expression was
      determined by real-time polymerase chain reaction (PCR). A novel in vitro model
      of fetal inflammation is described. Both adult and fetal endothelial cells
      demonstrated a dose-dependent increase in neutrophil adhesion and transmigration
      with increasing doses of TNF-alpha. The fetal response was significantly lower
      than the adult. As expected, rolling velocity was lower at higher cytokine
      concentrations and had an inverse correlation with P-selectin mRNA expression.
      Fetal endothelial cells are less permissive to adhesion and transmigration of
      neutrophils than adult endothelial cells. This may contribute to the paucity of
      inflammation seen in the fetal response to dermal injury.

PMID- 16306211
TI  - Nonprotein-bound iron and plasma protein oxidative stress at birth.
AB  - We previously reported plasma nonprotein-bound iron (NPBI) as a reliable early
      indicator of intrauterine oxidative stress (OS) and brain injury. We tested the
      hypothesis that albumin, an NPBI serum carrier, is the major target of NPBI
      induced OS. Twenty-four babies were randomly selected from 384 newborns
      constituting the final cohort of a prospective study undertaken to evaluate the
      predictive role of NPBI in cord blood for neurodevelopmental outcome. Twelve were
      selected in the group with lowest NPBI levels (0-1.16 microM) and good
      neurodevelopmental outcome and 12 in the group with highest NPBI levels (>or=15.2
      microM) and poor neurodevelopmental outcome. Protein carbonyl groups were
      identified in cord blood samples by two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE) and Western blotting with anti-2,4-dinitrophenyl (DNP)
      antibodies. Two series of immunoreactive spots, corresponding to serum albumin
      and alpha-fetoprotein, were found only in the group with highest NPBI levels. We
      found an association between NPBI and carbonylated proteins in babies with
      highest NPBI levels. Since NPBI may produce hydroxyl radicals through the Fenton
      reaction, the major target of OS induced by NPBI is its carrier: albumin.
      Oxidation of albumin can be expected to decrease plasma antioxidant defenses and
      increase the likelihood of tissue damage due to OS in the newborns.

PMID- 16306212
TI  - IgA antibodies, TGF-beta1 and -beta2, and soluble CD14 in the colostrum and
      development of atopy by age 4.
AB  - Specific defense factors in breast milk together with length of breast-feeding
      and genetic predisposition may modulate the development of allergy. We studied
      whether IgA, soluble CD14 (sCD14), or transforming growth factor (TGF)-beta in
      colostrum could affect the development of atopy in children up to age 4. From a
      cohort of 4676, we selected four groups of children with either long or short
      exclusive breast-feeding (>3.5 or <0.5 mo); these groups further differed in the
      presence or absence of atopic heredity. In colostrum from mothers, we measured
      total IgA, IgA antibodies to cow's milk (CM) and casein, sCD14, and TGF-beta1 and
      -beta2. The children were divided into three groups: those with no atopic
      symptoms or IgE, those with allergic symptoms, and those with both outcomes.
      Mothers of infants later showing atopic symptoms or, in addition, having IgE
      sensitization (verified atopy) had a lower concentration of IgA casein antibodies
      in their colostrum than did mothers of infants with no indication of atopy at age
      4. Low concentration of IgA casein antibodies was a significant risk for verified
      atopy. sCD14 levels were lower in colostrum of mothers with infants developing
      atopic symptoms and IgE sensitization than of those of infants with no atopy.
      Specific IgA antibodies to CM antigens and sCD14 in colostrum significantly
      associated with the appearance of both symptomatic and verified atopy by age 4.

PMID- 16306213
TI  - Induction of MCP1, CCR2, and iNOS expression in THP-1 macrophages by serum of
      children late after Kawasaki disease.
AB  - Evidence of premature atherosclerosis late after Kawasaki disease (KD) is
      accumulating. Given the potential roles of monocyte chemoattractant protein-1
      (MCP-1), chemokine receptor CCR-2, and inducible nitric oxide synthase (iNOS) in
      atherogenesis, we sought to determine whether serum obtained from children late
      after KD would induce expression of these genes in macrophages in vitro. A total
      of 79 subjects were studied, which comprised 57 KD patients, 33 of whom had
      coronary aneurysms, and 22 age-matched controls. Expression of MCP-1, CCR2, and
      iNOS mRNA in THP-1 macrophages in the presence of patient and control serum was
      quantified as a ratio to beta-actin mRNA and expressed as a percentage of
      control. MCP-1 expression was significantly increased in the presence of serum
      from patients with coronary aneurysms. Expression of CCR2 and iNOS was
      significantly increased when THP-1 macrophages were incubated with serum from
      patients with and without coronary aneurysms. The magnitude of induction of MCP
      1, CCR2, and iNOS or in combinations correlated positively with serum high
      sensitivity C-reactive protein (hs-CRP), and low-density lipoprotein (LDL)
      cholesterol levels and negatively with high-density lipoprotein (HDL) cholesterol
      level. In conclusion, the serum of patients with a history of KD induces
      expression of MCP-1, CCR2, and iNOS in THP-1 macrophages in vitro. Induction of
      these genes in vivo may be related to chronic inflammation and may have important
      implications for premature atherosclerosis.

PMID- 16306214
TI  - Introduction of the American Pediatric Society's 2005 John Howland Award
      Recipient, Mary Ellen Avery, M.D.

PMID- 16306215
TI  - Estrogen modulates the mechanical homeostasis of mouse arterial vessels through
      nitric oxide.
AB  - We have recently shown that estrogen causes vessel dilation through receptor
      mediated stimulation of nitric oxide (NO) production. Here, we hypothesize that
      estrogen modulates the mechanical homeostasis in the blood vessel wall through NO
      production. The mechanical properties of female ovariectomized (ovx) mice, female
      mice lacking the gene for endothelial NO synthase (eNOS(-/-)), and control female
      and male mice were studied to test the hypothesis. The femoral and carotid
      arteries and aorta were cannulated in situ and mechanically distended. The
      stress, strain, elastic modulus, and wall thickness of vessels in ovx and eNOS(-/
      ) mice, as well as intact female and male mice, were determined. Western blot and
      immunohistochemistry were used to assess eNOS protein expression in the aorta.
      Moreover, NO by-products of the femoral and carotid artery were determined by
      measuring the levels of nitrite and nitrate. Our results show that ovariectomy
      and eNOS(-/-) significantly decrease the strain in all arteries. Furthermore, the
      eNOS protein was significantly reduced in ovx mice. Finally, the NO metabolites
      were significantly decreased both in ovx and eNOS(-/-) mice. We found
      statistically significant correlations between the structural (wall thickness),
      mechanical (stress, strain, and elastic modulus), and biochemical parameters (NO
      by-products). These novel results connect NO to the structural and mechanical
      properties of the vessel wall. Hence, the effect of endogenous estrogen on the
      arterial mechanical properties is mediated by the regulation of NO derived from
      eNOS.

PMID- 16306216
TI  - Estimation of arterial and cardiopulmonary total peripheral resistance baroreflex
      gain values: validation by chronic arterial baroreceptor denervation.
AB  - Feedback control of total peripheral resistance (TPR) by the arterial and
      cardiopulmonary baroreflex systems is an important mechanism for short-term blood
      pressure regulation. Existing methods for measuring this TPR baroreflex mechanism
      typically aim to quantify only the gain value of one baroreflex system as it
      operates in open-loop conditions. As a result, the normal, integrated functioning
      of the arterial and cardiopulmonary baroreflex control of TPR remains to be fully
      elucidated. To this end, the laboratory of Mukkamala et al. (Mukkamala R, Toska
      K, and Cohen RJ. Am J Physiol Heart Circ Physiol 284: H947-H959, 2003) previously
      proposed a potentially noninvasive technique for estimating the closed-loop
      (dimensionless) gain values of the arterial TPR baroreflex (GA) and the
      cardiopulmonary TPR baroreflex (GC) by mathematical analysis of the subtle, beat
      to-beat fluctuations in arterial blood pressure, cardiac output, and stroke
      volume. Here, we review the technique with additional details and describe its
      experimental evaluation with respect to spontaneous hemodynamic variability
      measured from seven conscious dogs, before and after chronic arterial
      baroreceptor denervation. The technique was able to correctly predict the group
      average changes in GA and GC that have previously been shown to occur following
      chronic arterial baroreceptor denervation. That is, reflex control by the
      arterial TPR baroreflex was virtually abolished (GA = -2.1 +/- 0.6 to 0.3 +/-
      0.2; P < 0.05), while reflex control by the cardiopulmonary TPR baroreflex more
      than doubled (GC = -0.7 +/- 0.4 to -1.8 +/- 0.2; P < 0.05). With further
      successful experimental testing, the technique may ultimately be employed to
      advance the basic understanding of TPR baroreflex functioning in both humans and
      animals in health and disease.

PMID- 16306217
TI  - Spectral characteristics of skin sympathetic nerve activity in heat-stressed
      humans.
AB  - Skin sympathetic nerve activity (SSNA) exhibits low- and high-frequency spectral
      components in normothermic subjects. However, spectral characteristics of SSNA in
      heat-stressed subjects are unknown. Because the main components of the integrated
      SSNA during heat stress (sudomotor/vasodilator activities) are different from
      those during normothermia and cooling (vasoconstrictor activity), we hypothesize
      that spectral characteristics of SSNA in heat-stressed subjects will be different
      from those in subjects subjected to normothermia or cooling. In 17 healthy
      subjects, SSNA, electrocardiogram, arterial blood pressure (via Finapres),
      respiratory activity, and skin blood flow were recorded during normothermia and
      heat stress. In 7 of the 17 subjects, these variables were also recorded during
      cooling. Spectral characteristics of integrated SSNA, R-R interval, beat-by-beat
      mean blood pressure, skin blood flow variability, and respiratory excursions were
      assessed. Heat stress and cooling significantly increased total SSNA. SSNA
      spectral power in the low-frequency (0.03-0.15 Hz), high-frequency (0.15-0.45
      Hz), and very-high-frequency (0.45-2.5 Hz) regions was significantly elevated by
      heat stress and cooling. Interestingly, heat stress caused a greater relative
      increase of SSNA spectral power within the 0.45- to 2.5-Hz region than in the
      other spectral ranges; cooling did not show this effect. Differences in the SSNA
      spectral distribution between normothermia/cooling and heat stress may reflect
      different characteristics of central modulation of vasoconstrictor and
      sudomotor/vasodilator activities.

PMID- 16306218
TI  - HIV prevention outreach in commercial gay venues in large cities: evaluation
      findings from London.
AB  - Human immunodeficiency virus (HIV) prevention delivered in gay venues in US
      cities has been found to be effective in reducing HIV transmission in the 1990s
      but effects might not be generalizable to different times and settings. Doubts
      have been raised about: outreach's ability to address skills and explore personal
      behaviour; big-city commercial gay venues being appropriate sites for outreach
      because of gossip and social surveillance; and acceptability of outreach by
      professionals rather than 'popular opinion formers'. We evaluated coverage,
      feasibility, acceptability and perceived impact of venue-based HIV prevention
      outreach by professionals in London, employing observation, surveys and
      interviews with venue-users, and focus groups/semi-structured interviews with
      workers. We found high coverage especially among target groups. Addressing
      negotiation skills and personal behaviour was feasible but required worker
      motivation and skill. Social surveillance rarely impeded work. Gay men generally
      found outreach acceptable and useful, and professionals were not regarded
      negatively. Impact on knowledge was commonly reported; impacts on negotiation
      skills and reflection on personal behaviour were more common among men
      experiencing longer contacts. In conclusion, professional HIV prevention outreach
      in gay venues in large cities is a feasible and acceptable intervention with
      significant potential impacts. Workers need to be well briefed and trained to
      maximize impact.

PMID- 16306219
TI  - Cell adhesion molecules in the CNS.

PMID- 16306221
TI  - The BTB domain of the nuclear matrix protein NRP/B is required for neurite
      outgrowth.
AB  - The neuronal nuclear matrix protein, NRP/B, contains a BTB domain and kelch
      repeats and is expressed in primary neurons but not in primary glial cells. To
      examine the function of NRP/B in neurons, we analyzed the structure/function of
      the NRP/B-BTB domain and its role in neurite outgrowth. Based on three
      dimensional modeling of NRP/B, we generated an NRP/B-BTB mutant containing three
      mutations in the conserved amino acids D47A, H60A and R61D that was termed BTB
      mutant A. BTB mutant A significantly reduced the dimerization of NRP/B compared
      to wild-type NRP/B. The NRP/B-BTB domain was required for nuclear localization
      and mediated the association of NRP/B with p110RB through the TR subdomain within
      the B pocket of p110RB. Overexpression of wild-type NRP/B and NRP/B-BTB domain
      significantly induced neurite outgrowth in PC12 cells and enhanced the G0-G1 cell
      population by approximately 23% compared to the control cells, whereas NRP/B-BTB
      mutant A reduced neurite outgrowth by 70-80%, and inhibited NRP/B-p110RB
      association. Single cell microinjection of NRP/B-specific antibodies also blocked
      the neurite outgrowth of PC12 cells upon NGF stimulation. Interference of NRP/B
      expression by small interfering RNA (NRP/B-siRNA) inhibited neurite outgrowth and
      suppressed the NGF-induced outgrowth of neurites in PC12 cells. Additionally,
      p110RB phosphorylation at serine residue 795 was significantly reduced in PC12
      cells treated with NRP/B siRNA compared to those treated with control GFP-siRNA,
      indicating that p110RB is a downstream target of NRP/B. Thus, the BTB domain of
      NRP/B regulates neurite outgrowth through its interaction with the TR subdomain
      within the B pocket of p110RB, and the conserved amino acids D47A, H60A and R61D
      within this domain of NRP/B are crucial residues for neurite extension in
      neuronal cells. These findings support a role for the BTB-domain of NRP/B as an
      important regulator of neuronal differentiation.

PMID- 16306222
TI  - PtdIns(3)P accumulation in triple lipid-phosphatase-deletion mutants triggers
      lethal hyperactivation of the Rho1p/Pkc1p cell-integrity MAP kinase pathway.
AB  - In the budding yeast Saccharomyces cerevisiae, the regulation of
      phosphatidylinositol 3-phosphate [PtdIns(3)P] is an essential function shared by
      the myotubularin-related phosphatase Ymr1p and the synaptojanin-like phosphatases
      Sjl2p and Sjl3p. The aim of this study was to gain further insight into the
      mechanisms underlying the toxicity of PtdIns(3)P accumulation in ymr1Delta
      sjl2Delta sjl3Delta mutant cells. We conducted a genetic screen to isolate genes
      that, when overexpressed, would rescue the conditional lethality of ymr1Delta
      sjl2Delta sjl3Delta triple-mutant cells expressing YMR1 from the dextrose
      repressible GAL1 promoter. This approach identified 17 genes that promoted growth
      of the triple mutant on media containing dextrose. Interestingly, the most
      frequently isolated gene product was a truncated form of PKC1 (Pkc1-T615) that
      lacked the C-terminal kinase domain. This Pkc1-T615 fragment also rescued the
      lethality of ymr1ts sjl2Delta sjl3Delta cells at restrictive temperature, and
      further mapping of the rescuing activity showed that the N-terminal Rho1-GTP
      interacting HR1 domains (Pkc1-T242) were sufficient. This indicated that the PKC1
      fragments might act by interfering with Rho1-GTP signal propagation. Consistent
      with this, deletion of the ROM2 gene, which encodes a major Rho1p guanine
      nucleotide exchange factor, bypassed the lethal effect of PtdIns(3)P accumulation
      in ymr1Delta sjl2Delta sjl3Delta triple-mutant cells. Furthermore, cells
      deficient in phosphoinositide 3-phosphatase (PI 3-phosphatase) activity were
      defective for Rho1p/Pkc1p pathway regulation, which included an inability of
      these cells to adapt to heat stress. Taken together, the results of this study
      indicated that aberrant Rho1p/Pkc1p signaling contributes to the lethal effects
      of PtdIns(3)P accumulation in cells deficient in PI 3-phosphatase activity.

PMID- 16306220
TI  - The axonal transport of mitochondria.
AB  - Organelle transport is vital for the development and maintenance of axons, in
      which the distances between sites of organelle biogenesis, function, and
      recycling or degradation can be vast. Movement of mitochondria in axons can serve
      as a general model for how all organelles move: mitochondria are easy to
      identify, they move along both microtubule and actin tracks, they pause and
      change direction, and their transport is modulated in response to physiological
      signals. However, they can be distinguished from other axonal organelles by the
      complexity of their movement and their unique functions in aerobic metabolism,
      calcium homeostasis and cell death. Mitochondria are thus of special interest in
      relating defects in axonal transport to neuropathies and degenerative diseases of
      the nervous system. Studies of mitochondrial transport in axons are beginning to
      illuminate fundamental aspects of the distribution mechanism. They use motors of
      one or more kinesin families, along with cytoplasmic dynein, to translocate along
      microtubules, and bidirectional movement may be coordinated through interaction
      between dynein and kinesin-1. Translocation along actin filaments is probably
      driven by myosin V, but the protein(s) that mediate docking with actin filaments
      remain unknown. Signaling through the PI 3-kinase pathway has been implicated in
      regulation of mitochondrial movement and docking in the axon, and additional
      mitochondrial linker and regulatory proteins, such as Milton and Miro, have
      recently been described.

PMID- 16306223
TI  - Re-defining the Golgi complex in Plasmodium falciparum using the novel Golgi
      marker PfGRASP.
AB  - Plasmodium falciparum, the causative agent of malaria, relies on a sophisticated
      protein secretion system for host cell invasion and transformation. Although the
      parasite displays a secretory pathway similar to those of all eukaryotic
      organisms, a classical Golgi apparatus has never been described. We identified
      and characterised the putative Golgi matrix protein PfGRASP, a homologue of the
      Golgi re-assembly stacking protein (GRASP) family. We show that PfGRASP is
      expressed as a 70 kDa protein throughout the asexual life cycle of the parasite.
      We generated PfGRASP-GFP-expressing transgenic parasites and showed that this
      protein is localised to a single, juxtanuclear compartment in ring-stage
      parasites. The PfGRASP compartment is distinct from the ER, restricted within the
      boundaries of the parasite and colocalises with the cis-Golgi marker ERD2.
      Correct subcellular localisation of this Golgi matrix protein depends on a cross
      species conserved functional myristoylation motif and is insensitive to Brefeldin
      A. Taken together our results define the Golgi apparatus in Plasmodium and depict
      the morphological organisation of the organelle throughout the asexual life cycle
      of the parasite.

PMID- 16306224
TI  - Carboxyamidotriazole-induced inhibition of mitochondrial calcium import blocks
      capacitative calcium entry and cell proliferation in HEK-293 cells.
AB  - Blocking calcium entry may prevent normal and pathological cell proliferation.
      There is evidence suggesting that molecules such as carboxyamidotriazole, widely
      used in anti-cancer therapy based on its ability to block calcium entry in
      nonexcitable cells, also have antiproliferative properties. We found that
      carboxyamidotriazole and the capacitative calcium entry blocker 2
      aminoethoxydiphenyl borate inhibited proliferation in HEK-293 cells with IC50
      values of 1.6 and 50 microM, respectively. Capacitative calcium entry is
      activated as a result of intracellular calcium store depletion. However, non
      capacitative calcium entry pathways exist that are independent of store depletion
      and are activated by arachidonic acid and diacylglycerol, generated subsequent to
      G protein coupled receptor stimulation. We found that carboxyamidotriazole
      completely inhibited the capacitative calcium entry and had no effect on the
      amplitude of arachidonic-acid-activated non-capacitative calcium entry. However,
      investigation of the effects of carboxyamidotriazole on mitochondrial calcium
      dynamics induced by carbachol, capacitative calcium entry and exogenously set
      calcium loads in intact and digitonin-permeabilized cells revealed that
      carboxyamidotriazole inhibited both calcium entry and mitochondrial calcium
      uptake in a time-dependent manner. Mitochondrial inner-membrane potential was
      altered by carboxyamidotriazole treatment, suggesting that carboxyamidotriazole
      antagonizes mitochondrial calcium import and thus local calcium clearance, which
      is crucial for the maintenance of capacitative calcium entry.

PMID- 16306225
TI  - CysLT1 receptor is a target for extracellular nucleotide-induced heterologous
      desensitization: a possible feedback mechanism in inflammation.
AB  - Both cysteinyl-leukotrienes and extracellular nucleotides mediate inflammatory
      responses via specific G-protein-coupled receptors, the CysLT and the P2Y
      receptors, respectively. Since these mediators accumulate at sites of
      inflammation, and inflammatory cells express both classes of receptors, their
      responses are likely to be crossregulated. We investigated the molecular basis of
      desensitization and trafficking of the CysLT1 receptor constitutively and
      transiently expressed in the human monocyte/macrophage-like U937 or COS-7 cells
      in response to LTD4 or nucleotides. Exposure to agonist induced a rapid
      homologous desensitization of the CysLT1 receptor [as measured by the reduction
      in the maximal agonist-induced intracellular cytosolic Ca2+ ([Ca2+]i) transient],
      followed by receptor internalization (as assessed by equilibrium binding and
      confocal microscopy). Activation of P2Y receptors with ATP or UDP induced
      heterologous desensitization of the CysLT1 receptor. Conversely, LTD4-induced
      CysLT1 receptor activation had no effect on P2Y receptor responses, which
      suggests that the latter have a hierarchy in producing desensitizing signals.
      Furthermore, ATP/UDP-induced CysLT1 receptor desensitization was unable to cause
      receptor internalization, induced a faster recovery of CysLT1 functionality and
      was dependent upon protein kinase C. By contrast, homologous desensitization,
      which is probably dependent upon G-protein-receptor kinase 2 activation, induced
      a fast receptor downregulation and, accordingly, a slower recovery of CysLT1
      functionality. Hence, CysLT1 receptor desensitization and trafficking are
      differentially regulated by the CysLT1 cognate ligand or by extracellular
      nucleotides. This crosstalk may have a profound physiological implication in the
      regulation of responses at sites of inflammation, and may represent just an
      example of a feedback mechanism used by cells to fine-tune their responses.

PMID- 16306226
TI  - The mAKAP complex participates in the induction of cardiac myocyte hypertrophy by
      adrenergic receptor signaling.
AB  - Maladaptive cardiac hypertrophy can progress to congestive heart failure, a
      leading cause of morbidity and mortality in the United States. A better
      understanding of the intracellular signal transduction network that controls
      myocyte cell growth may suggest new therapeutic directions. mAKAP is a scaffold
      protein that has recently been shown to coordinate signal transduction enzymes
      important for cytokine-induced cardiac hypertrophy. We now extend this
      observation and show mAKAP is important for adrenergic-mediated hypertrophy. One
      function of the mAKAP complex is to facilitate cAMP-dependent protein kinase A
      catalyzed phosphorylation of the ryanodine receptor Ca2+-release channel.
      Experiments utilizing inhibition of the ryanodine receptor, RNA interference of
      mAKAP expression and replacement of endogenous mAKAP with a mutant form that does
      not bind to protein kinase A demonstrate that the mAKAP complex contributes to
      pro-hypertrophic signaling. Further, we show that calcineurin Abeta associates
      with mAKAP and that the formation of the mAKAP complex is required for the full
      activation of the pro-hypertrophic transcription factor NFATc. These data reveal
      a novel function of the mAKAP complex involving the integration of cAMP and Ca2+
      signals that promote myocyte hypertrophy.

PMID- 16306227
TI  - SV2A and SV2C are not vesicular Ca2+ transporters but control glucose-evoked
      granule recruitment.
AB  - Synaptic vesicle protein 2 (SV2) is expressed in neuroendocrine cells as three
      homologous isoforms, SV2A, SV2B and SV2C. Ca2+-dependent function in exocytosis
      has been attributed to SV2A and SV2B, without elucidation of the mechanism. The
      role of SV2C has not yet been addressed. Here we characterize the three SV2
      isoforms and define their involvement in regulated insulin secretion. SV2A and
      SV2C are associated with insulin-containing granules and synaptic-like
      microvesicles (SLM) in INS-1E insulinoma and primary beta-cells, whereas SV2B is
      only present on SLM. Neither overexpression nor isoform-specific silencing of
      SV2A or SV2C by RNA interference modifies depolarization-triggered cytosolic
      [Ca2+] rises or secretory granule [Ca2+], measured with a VAMP-2 aequorin
      chimera. This strongly argues against any Ca2+ transport function of SV2.
      Moreover, up- or downregulation of these isoforms has no influence on K+-induced
      insulin release suggesting that SV2 does not affect the Ca2+-dependent step(s) of
      exocytosis. By contrast, glucose-elicited secretion is inhibited during the
      sustained rather than the early phase, placing the action of SV2 on the
      recruitment of granules from the reserve pool to the plasma membrane. This
      conclusion is reinforced by capacitance measurements in glucose-stimulated SV2C
      deficient cells. Like capacitance, evoked and basal hormone release are
      attenuated more by silencing of SV2C compared with SV2A. This indicates only
      partial redundancy and highlights a key role for SV2C in the secretory process.

PMID- 16306228
TI  - 14-3-3 cooperates with LKB1 to regulate the activity and localization of QSK and
      SIK.
AB  - The LKB1 tumour suppressor kinase phosphorylates and activates a number of
      protein kinases belonging to the AMP-activated protein kinase (AMPK) subfamily.
      We have used a modified tandem affinity purification strategy to identify
      proteins that interact with AMPKalpha, as well as the twelve AMPK-related kinases
      that are activated by LKB1. The AMPKbeta and AMPKgamma regulatory subunits were
      associated with AMPKalpha, but not with any of the AMPK-related kinases,
      explaining why AMP does not influence the activity of these enzymes. In addition,
      we identified novel binding partners that interacted with one or more of the AMPK
      subfamily enzymes, including fat facets/ubiquitin specific protease-9 (USP9), AAA
      ATPase-p97, adenine nucleotide translocase, protein phosphatase 2A holoenzyme and
      isoforms of the phospho-protein binding adaptor 14-3-3. Interestingly, the 14-3-3
      isoforms bound directly to the T-loop Thr residue of QSK and SIK, after these
      were phosphorylated by LKB1. Consistent with this, the 14-3-3 isoforms failed to
      interact with non-phosphorylated QSK and SIK, in LKB1 knockout muscle or in HeLa
      cells in which LKB1 is not expressed. Moreover, mutation of the T-loop Thr
      phosphorylated by LKB1, prevented QSK and SIK from interacting with 14-3-3 in
      vitro. Binding of 14-3-3 to QSK and SIK, enhanced catalytic activity towards the
      TORC2 protein and the AMARA peptide, and was required for the cytoplasmic
      localization of SIK and for localization of QSK to punctate structures within the
      cytoplasm. To our knowledge, this study provides the first example of 14-3-3
      binding directly to the T-loop of a protein kinase and influencing its catalytic
      activity and cellular localization.

PMID- 16306229
TI  - Presynaptic mechanism underlying cAMP-induced synaptic potentiation in medial
      prefrontal cortex pyramidal neurons.
AB  - cAMP, a classic second messenger, has been proposed recently to participate in
      regulating prefrontal cortical cognitive functions, yet little is known about how
      it does so. In this study, we used forskolin, an adenylyl cyclase activator, to
      examine the effects of cAMP on excitatory synaptic transmission in the medial
      prefrontal cortex (mPFC) using whole-cell patch-clamp recordings from visually
      identified layer II-III or V pyramidal cells in vitro. We found that bath
      application of forskolin significantly increased the amplitude of excitatory
      postsynaptic currents (EPSCs) in a concentration- and age-dependent manner. This
      enhancement was completely abolished by coapplication of cAMP-dependent protein
      kinase (PKA) inhibitor and p42/p44 mitogen-activated protein kinase (MAPK) kinase
      inhibitor, but not application of either drug alone. The membrane-permeable cAMP
      analog adenosine 3',5'-cyclic monophosphorothioate, Sp-isomer, triethylammonium
      salt, or activation of beta-adrenergic receptor by isoproterenol mimicked the
      effect of forskolin to potentiate EPSCs. However, neither exchange protein
      activated by cAMP (Epac) inhibitor brefeldin A nor hyperpolarization and cyclic
      nucleotide-activated channel blocker 4-ethylphenylamino-1,2-dimethyl-6
      methylaminopyrimidinium chloride (ZD7288) affected forskolin response. The
      augmentation of EPSCs by forskolin was accompanied by a reduction of the synaptic
      failure rate, coefficient of variation and paired-pulse ratio of EPSCs, and an
      increase in release probability and number of releasable synaptic vesicles.
      Forskolin also significantly increased the frequency of miniature EPSCs without
      altering their amplitude distribution. These results indicate that cAMP acts
      presynaptically to elicit a synaptic potentiation on the layer V pyramidal
      neurons of mPFC through converging activation of PKA and p42/p44 MAPK signaling
      pathways.

PMID- 16306230
TI  - Insulin-like growth factor binding protein-2: contributions of the C-terminal
      domain to insulin-like growth factor-1 binding.
AB  - Signaling by the insulin-like growth factor (IGF)-1 receptor (IGF-1R) has been
      implicated in the promotion and aggressiveness of breast, prostate, colorectal,
      and lung cancers. The IGF binding proteins (IGFBPs) represent a class of natural
      IGF antagonists that bind to and sequester IGF-1/2 from the IGF-1R, making them
      attractive candidates as therapeutics for cancer prevention and control.
      Recombinant human IGFBP-2 significantly attenuated IGF-1-stimulated MCF-7 cell
      proliferation with coaddition of 20 or 100 nM IGFBP-2 (50 or 80% inhibition,
      respectively). We previously identified IGF-1 contact sites both upstream and
      downstream of the CWCV motif (residues 247-250) in human IGFBP-2 (J Biol Chem
      276:2880-2889, 2001). To further test their contributions to IGFBP-2 function,
      the single tryptophan in human IGFBP-2, Trp-248, was selectively cleaved with 2
      (2'nitrophenylsulfenyl)-3-methyl-3 bromoindolenine (BNPS-skatole) and the BNPS
      skatole products IGFBP-2(1-248) and IGFBP-2(249-289) as well as IGFBP-2(1-190)
      were expressed as glutathione S-transferase-fusion proteins and purified. Based
      on competition binding analysis, deletion of residues 249 to 289 caused an
      approximately 20-fold decrease in IGF-1 binding affinity (IGFBP-2 EC50 = 0.35 nM
      and IGFBP-2(1-248) = 7 nM). Removal of the remainder of the C-terminal domain had
      no further effect on affinity (IGFBP-2(1-190) EC50 = 9.2 nM). In kinetic assays,
      IGFBP-2(1-248) and IGFBP-2(1-190) exhibited more rapid association and
      dissociation rates than full-length IGFBP-2. These results confirm that regions
      upstream and downstream of the CWCV motif participate in IGF-1 binding. They
      further support the development of full-length IGFBP-2 as a cancer therapeutic.

PMID- 16306231
TI  - Identification of zebrafish ARNT1 homologs: 2,3,7,8-tetrachlorodibenzo-p-dioxin
      toxicity in the developing zebrafish requires ARNT1.
AB  - To use the zebrafish (Danio rerio) as a model to study 2,3,7,8-tetrachlorodibenzo
      p-dioxin (TCDD) developmental toxicity, it is essential to know which proteins
      are involved in mediating toxicity. Previous work has identified zfAHR2 as the
      receptor that binds TCDD mediating downstream responses. Although zfARNT2b can
      form a functional heterodimer with zfAHR2 in vitro, zfarnt2 null mutants show no
      protection against endpoints of TCDD developmental toxicity, demonstrating that
      zfARNT2b cannot be the physiological dimerization partner for zfAHR2 mediating
      responses to TCDD in zebrafish embryos. The purpose of the current study was to
      identify an alternate dimerization partner(s) for zfAHR2 that may function to
      mediate TCDD developmental toxicity. By searching zebrafish genomic sequence and
      using the polymerase chain reaction-based rapid amplification of cDNA ends
      technique, three forms of cDNA that seem to be alternate mRNA splice variants of
      a zebrafish homolog of ARNT1 were detected. Analysis of the zfARNT1 proteins in
      vitro demonstrates that the two longest forms of zfARNT1, zfARNT1b and zfARNT1c,
      can form functional heterodimers with zfAHR2. However, the shortest form,
      zfARNT1a, seems to be nonfunctional with zfAHR2 in vitro. To determine whether a
      zfARNT1 protein functions with zfAHR2 in vivo, a morpholino targeted against the
      5' end of zfARNT1 (zfarnt1-MO) was used. Injection of the zfarnt1-MO before TCDD
      treatment significantly decreases the induction of zfCYP1A mRNA and protein. In
      addition, zfarnt1 morphants show complete protection against TCDD-induced
      pericardial edema and show partial protection against reduced blood flow and
      craniofacial malformations caused by TCDD, demonstrating the role of zfARNT1
      proteins in mediating these responses.

PMID- 16306232
TI  - Heme deficiency is associated with senescence and causes suppression of N-methyl
      D-aspartate receptor subunits expression in primary cortical neurons.
AB  - Heme is a crucial component of many pharmacological and toxicological processes,
      and studies have suggested that heme deficiency may play a role in cellular
      ageing. A model of ageing neurons was established using prolonged cultures of
      BALB/c mouse primary cortical neurons. Aged neurons displayed a senescent
      phenotype and a marked up-regulation of cathepsin-L expression. Down-regulation
      of the candidate neuron-specific genes for N-methyl-D-aspartate (NMDA) receptor
      subunits (NMDAzeta1 and -epsilon2) and neurofilament light peptide (NF-L) were
      found to be characteristic of the aging process as reported in vivo (Brain Res
      907:71-83, 2001; Brain Res Mol Brain Res 99:40-45, 2002). In contrast, the genes
      for the controlling enzymes of heme synthesis and degradation (5-aminolevulinate
      synthase 1 and heme oxygenase 1, respectively) were up-regulated, implying
      depletion of a regulatory heme pool. Inhibition of heme synthesis (by 70-80%) at
      different enzymic steps by succinyl acetone and N-methylprotoporphyrin IX
      resulted in the earlier lowered expression of NMDAzeta1 and -epsilon2 and NF-L.
      Exogenous hemin added to heme-depleted cells rescued the expression of these
      neuron-specific genes. Culture of cortical neurons from BALB/c Fech(m1Pas) mutant
      mice demonstrating depressed heme synthesis showed premature senescence and
      reduced expression of NMDAzeta1 and -epsilon2 receptor subunits and NF-L compared
      with wild-type cells. Our findings suggest that reduced availability of heme in
      neurons associated with senescence may have significant effects on synaptic
      function.

PMID- 16306233
TI  - In vivo selection of engineered homing endonucleases using double-strand break
      induced homologous recombination.
AB  - Homing endonucleases, endonucleases capable of recognizing long DNA sequences,
      have been shown to be a tool of choice for precise and efficient genome
      engineering. Consequently, the possibility to engineer novel endonucleases with
      tailored specificities is under strong investigation. In this report, we present
      a simple and efficient method to select meganucleases from libraries of variants,
      based on their cleavage properties. The method has the advantage of directly
      selecting for the ability to induce double-strand break induced homologous
      recombination in a eukaryotic environment. Model selections demonstrated high
      levels of enrichments. Moreover, this method compared favorably with phage
      display for enrichment of active mutants from a mutant library. This approach
      makes possible the exploration of large sequence spaces and thereby represents a
      valuable tool for genome engineering.

PMID- 16306235
TI  - Phylloxera and the grapevine: a sense of common purpose?
AB  - The purpose of life is its continuation: survival is the reason things live. Here
      we explore this 'basic' of biology, by reference to the extraordinary life-cycle
      of the aphid-like pest phylloxera, and the complexity of its relationship with
      its host the grapevine. The effort and ingenuity that phylloxera employs to
      continue itself leads to a doubt that survival alone is sufficient reason. It has
      frequently been suggested that the reduction of life to a catalogue of facts (by
      science) creates this doubt, because it robs existence of its essence (which is
      something other than its mechanics). The part that science is said to steal is
      what Robert Pirsig calls Quality-the harmonious balance of things. Pirsig seems
      to imply that this is something inherent in things-and independent from us. A
      more mundane explanation is that the difference between facts and the complete
      reality is us-the tendency of mind to connect freely between different kinds of
      information. This possibility is briefly illustrated here by a myth based on the
      facts of phylloxera.

PMID- 16306234
TI  - Minimal pre-mRNA substrates with natural and converted sites for full-round U
      insertion and U deletion RNA editing in trypanosomes.
AB  - Trypanosome RNA editing by uridylate insertion or deletion cycles is a
      mitochondrial mRNA maturation process catalyzed by multisubunit complexes. A full
      round of editing entails three consecutive steps directed by partially
      complementary guide RNAs: pre-mRNA cleavage, U addition or removal, and ligation.
      The structural and functional composition of editing complexes is intensively
      studied, but their molecular interactions in and around editing sites are not
      completely understood. In this study, we performed a systematic analysis of
      distal RNA requirements for full-round insertion and deletion by purified
      editosomes. We define minimal substrates for efficient editing of A6 and CYb
      model transcripts, and established a new substrate, RPS12. Important differences
      were observed in the composition of substrates for insertion and deletion.
      Furthermore, we also showed for the first time that natural sites can be
      artificially converted in both directions: from deletion to insertion or from
      insertion to deletion. Our site conversions enabled a direct comparison of the
      two editing kinds at common sites during substrate minimization and demonstrate
      that all basic determinants directing the editosome to carry out full-round
      insertion or deletion reside within each editing site. Surprisingly, we were able
      to engineer a deletion site into CYb, which exclusively undergoes insertion in
      nature.

PMID- 16306236
TI  - Children of Alzheimer patients: an overview.

PMID- 16306237
TI  - Middle-aged children of Alzheimer parents, a pilot study: stable neurocognitive
      performance at 20-year follow-up.
AB  - The objective of this pilot study on a convenience sample of 25 offspring of
      Alzheimer patients (mean age 61.5 +/- 8.8 years; range, 50-82) was the early
      detection of neurocognitive decline. This preliminary report appears to be the
      first one dealing with 20-year follow-up of neurocognitive data of Alzheimer's
      disease (AD) children. Digit symbol (Wechsler Adult Intelligence Scale) was the
      only of 11 neurocognitive measures with a significant decline. And that decline
      between first and last testing (mean = 19.98 +/- 0.30 years) was on raw scores,
      not scaled scores. Neither parents' age at onset of AD nor autopsy confirmation
      or offspring APOE-e4 status influenced neurocognitive results. More robust data
      than currently available are needed to confirm the findings of this first pilot
      study and to determine both the trajectory of neurocognitive decline in AD and
      the risks of developing AD faced by children whose parent had the disease.

PMID- 16306238
TI  - Predicting Alzheimer's disease in the Baltimore longitudinal study of aging.
AB  - Longitudinal studies offer opportunities for studying children whose parents have
      Alzheimer's disease. The Baltimore Longitudinal Study of Aging (BLSA) has
      examined adult cognitive performance but has not systematically recruited
      participants' children. We initiated studies of dementia in the 1980s. This work
      suggested that hormone replacement and use of nonsteroidal anti-inflammatory
      drugs reduced the risk of Alzheimer's disease and that risk for Alzheimer's
      disease could be predicted from cognitive performance as many as 20 years prior
      to its onset. More recently, we showed that premorbid levels of free testosterone
      were lower in men who developed Alzheimer's disease and premorbid depressive
      symptomatology was a risk for Alzheimer's disease in men but not women as many as
      6 years before the onset of dementia. Participants in the BLSA include family
      members with a variety of degrees of relationship, but there is no systematic
      effort to collect data from relatives of participants.

PMID- 16306239
TI  - Apolipoprotein E epsilon4 and change in cognitive functioning in community
      dwelling older adults.
AB  - The relationship between apolipoprotein E (APOE) epsilon4 and change in cognition
      was examined in older men (n = 247; age = 75.0 +/- 3.5 years) and women (n = 79;
      age = 70.8 +/- 4.9 years) free of history of stroke. Participants were examined
      again 4.0 +/- 0.5 years later. Exclusion criteria were (1) initial scores on the
      Mini-Mental State Examination of 23 or less or (2) the presence of the APOE 2/4
      genotype. Men with epsilon4 showed greater decline in some measures of executive
      function and verbal memory compared to those without epsilon4; women with
      epsilon4 showed greater decline in Trail Making test performance relative to
      women without the allele. A significant gender x APOE epsilon4 interaction was
      seen for change in performance on short delay cued recall. These results suggest
      that APOE epsilon4 is associated with cognitive decline differently in older
      adult men and women.

PMID- 16306240
TI  - Performance on neurocognitive tests by co-twins to dementia cases compared to
      normal control twins.
AB  - Nondemented co-twins of twins who were diagnosed as demented were compared to
      randomly selected members of normal control twin pairs in which both members of
      the pair were nondemented. Nondemented co-twins included 23 monozygotic and 62
      dizygotic twins; there were 27 normal control twins. Both monozygotic and
      dizygotic nondemented co-twins of dementia cases scored significantly lower than
      normal control twins on 5 of 10 cognitive tests. Moreover, monozygotic co-twins
      of dementia cases had a generally lower score profile than dizygotic co-twins of
      dementia cases did. These findings show that being at greater genetic risk for
      dementia is reflected in cognitive performance even in the absence of a diagnosis
      of dementia.

PMID- 16306241
TI  - Similar neurocognitive performance of adults with and without a history of
      parental Alzheimer's disease: a pilot study.
AB  - The first reported 20-year prospective follow-up of middle-aged children of
      Alzheimer patients failed to find statistically significant neurocognitive
      decline. Because that report did not include a comparison group, the current
      study compared the 20-year follow-up scores with scores obtained on the same 8
      measures by an age-comparable sample of healthy adults without a family history
      of Alzheimer's disease. Both were convenience samples (n = 24). Statistical
      analyses (correcting for age) yielded no significant group differences in
      neurocognitive scores but did show a significantly higher mean score for the
      comparison group on the Mini-Mental State Examination (29.5 vs 28.8, P = .003,
      controlling for age). Even though this finding suggests that adult children of a
      parent with Alzheimer's disease performed well on a limited neurocognitive
      battery and on the Mini-Mental State Examination, the findings are preliminary
      and require confirmation on large representative samples with appropriate
      controls and long-term follow-up.

PMID- 16306242
TI  - Cognitive decline and literacy among ethnically diverse elders.
AB  - Researchers on genetic and environmental influences on risk for Alzheimer's
      disease must be prepared for the growing ethnic and racial diversity of our
      participants. Within the investigation, years of education has typically served
      as a proxy for cognitive reserve, which may be one factor in influencing risk of
      cognitive decline among aging people. However, among ethnic minorities, years of
      education is a poor reflection of the value of educational experience and native
      ability. This study was conducted among 1002 ethnically diverse English-speaking
      residents of Northern Manhattan who were cognitively and functionally normal at a
      baseline evaluation. We found that literacy level was a better predictor of
      decline in memory, executive function, and language skills than was years of
      education. The results of this study suggest that in an ethnically diverse
      cohort, literacy level should be considered as a mediator of the interactions of
      biological and environmental factors on cognitive decline.

PMID- 16306243
TI  - Very early detection of Alzheimer neuropathology and the role of brain reserve in
      modifying its clinical expression.
AB  - Numerous studies show that the pathology of Alzheimer's disease is present
      decades before a clinical diagnosis of dementia can be made. Given the likelihood
      that agents will become available that reliably delay onset and/or slow
      progression of Alzheimer's disease, it will be important to detect preclinical
      Alzheimer's disease as early as possible for maximal treatment effect. Detection
      of individuals by sensitive cognitive measures provides one way to identify
      people who are at high risk of developing clinical Alzheimer's disease. However,
      it is likely that those with considerable brain or cognitive reserve will be able
      to mask cognitive deficits until very close to the onset of the dementia,
      rendering such cognitive measures insensitive. Optimum biomarkers for Alzheimer's
      disease therefore need to target the severity of underlying brain pathology
      independently of brain reserve. Findings are presented showing the importance of
      higher education and larger brain size in masking the underlying disease
      pathology.

PMID- 16306244
TI  - Recent clinical-pathologic research on the causes of dementia in late life:
      update from the Honolulu-Asia Aging Study.
AB  - In this study, we compare neuropathological findings at autopsy with clinical
      dementia diagnoses, such as Alzheimer's disease and vascular dementia.
      Participants consisted of 363 aged Japanese-American men from the Honolulu-Asia
      Aging Study. Results indicated that the correspondence between clinical and
      neuropathologic diagnosis was not great, with 56% of patients diagnosed with
      probable or possible Alzheimer's disease during life but with only 19% having
      neuritic plaques and/or neurofibrillary tangles as the sole or dominant dementia
      related lesions in the brain at autopsy. Although 16% of cases were attributed to
      mixed causes during life, almost 40% were found to have significant mixtures of
      dementia-related lesions at autopsy. Finally, both Alzheimer's disease and non
      Alzheimer's disease neuropathologic lesions contributed independently to the
      explanation of variance on a test of overall cognitive performance. The results
      suggest that clinical diagnosis of dementia made during life may fail to reflect
      the pathogenic complexity of this condition in very elderly persons.

PMID- 16306245
TI  - What the study of persons at risk for familial Alzheimer's disease can tell us
      about the earliest stages of the disorder: a review.
AB  - As the proportion of elderly persons continues to expand, understanding the
      pathobiology of Alzheimer's disease and being able to diagnose it at an early
      stage become more critical. A minority of Alzheimer's disease cases are inherited
      as a fully-penetrant, autosomal dominant trait with a young age of onset. The
      molecular study of the pathogenic mutations has led to insights regarding the
      etiology of sporadic Alzheimer's disease. Clinical studies in persons at risk for
      these mutations have confirmed early episodic memory and executive deficits in
      Alzheimer's disease and suggested that dysphoria may precede the cognitive
      changes of Alzheimer's disease. Imaging studies have indicated that medial
      temporal lobe atrophy begins 3 to 4 years before cognitive symptoms, and
      quantitative cerebral metabolic changes are also present from early on. Studies
      of biochemical markers suggest that elevations of plasma A 1-42 occur early in
      familial Alzheimer's disease but that tau may not be elevated in cerebrospinal
      fluid until the disease is more advanced.

PMID- 16306246
TI  - Longitudinal models of growth and survival applied to the early detection of
      Alzheimer's disease.
AB  - This article explores new statistical methodologies for using longitudinal data
      in the early prediction of Alzheimer's disease (AD). Specifically, the authors
      examine some new techniques that allow the joint or "shared" estimation of
      longitudinal components based on both duration (survival) and quantitative
      changes (growth curves). These new shared growth-survival parameter models may be
      used to characterize the declining functions that anticipate the onset of AD. The
      authors apply these models to data from the Kungsholmen Project, a longitudinal
      study of aging in Stockholm, Sweden. They examine age-based survival-frailty
      models for the onset of AD, latent growth-decline curve models for changes in
      cognition over age, and 3 alternative forms of models for the shared
      relationships of survival and early cognitive decline. The accuracy and
      reliability of this approach is considered for a better understanding of the
      developmental course of AD in these data, including the potential removal of
      biases due to subject selection.

PMID- 16306247
TI  - Antecedent biomarkers of Alzheimer's disease: the adult children study.
AB  - The Washington University Adult Children Study is a longitudinal study to develop
      and validate biological markers, imaging features, and other indicators of
      preclinical Alzheimer's disease to aid in identifying individuals at high risk
      for developing symptomatic Alzheimer's disease. Two groups of participants
      between the ages of 45 and 74 are being enrolled in the Adult Children Study.
      Group 1 represents adult children who have at least 1 parent with Alzheimer's
      disease. Group 2 represents adult children whose parents have lived at least to
      age 70 without dementia. The Adult Children Study participants have been highly
      motivated to participate, and this study will require the investment of many
      years from the participants and the investigators before its most significant
      results will be known.

PMID- 16306248
TI  - Middle-aged children of persons with Alzheimer's disease: APOE genotypes and
      cognitive function in the Wisconsin Registry for Alzheimer's Prevention.
AB  - Adult children of persons with Alzheimer's disease are at increased risk of
      developing Alzheimer's disease because of hereditary, environmental, and health
      risk factors shared with affected parents. The Wisconsin Registry for Alzheimer's
      Prevention (WRAP) has completed baseline assessments on 452 middle-aged persons
      (mean = 53 years) who have at least 1 parent with AD. Forty-five percent had 1 or
      more apolipoprotein (APOE) epsilon4 alleles. There were few significant
      differences between epsilon4 carriers and noncarriers in demographics, health,
      and lifestyle measures or in neuropsychological performance. The high percentage
      of WRAP participants who are carriers of APOE epsilon4 underscores their
      increased risk for developing Alzheimer's disease, but the absence of differences
      related to APOE status and high mean scores on cognitive tests suggests that the
      APOE epsilon4 gene has yet to have a clinical impact on cognitive functioning.
      The WRAP cohort may be a valuable group to follow prospectively to characterize
      the nature of cognitive change in relation to risk factors and to identify
      underlying preclinical neurobiological changes.

PMID- 16306249
TI  - Genetic risk assessment for adult children of people with Alzheimer's disease:
      the Risk Evaluation and Education for Alzheimer's Disease (REVEAL) study.
AB  - As genetic risk factors continue to be identified for common, complex adult-onset
      diseases, it will become increasingly important to understand if, how, and when
      to translate these discoveries into clinical practice. This article provides an
      overview of and results to date from the REVEAL study, a multisite randomized
      clinical trial (n = 162) examining the impact of a genetic risk assessment
      program, including apolipoprotein E genotype disclosure, for adult children of
      people with Alzheimer's disease. The study's rationale and procedures are
      described, including the generation of numerical lifetime risk curves for use in
      the education and counseling protocol. Findings are summarized across numerous
      study questions, including (1) who seeks genetic risk assessment and why, (2) how
      apolipoprotein E results affect risk perceptions, (3) the psychological impact of
      genetic risk assessment, and (4) how risk information affects participants'
      subsequent health and insurance behaviors.

PMID- 16306251
TI  - Single-breath test in lateral decubitus reflects function of single lungs grafted
      for emphysema.
AB  - The slope of alveolar plateau for nitrogen derived from the single-breath test is
      useful to assess the function of bilateral lung grafts, but this technique is not
      applicable to patients with single-lung grafts due to the confounding influence
      of the native lung. We tested the hypothesis that the nitrogen slope measured in
      lateral decubitus with the graft in nondependent position may primarily reflect
      the distribution of ventilation in this lung. Fifteen patients with single-lung
      transplantation for emphysema, 10 healthy controls, and 7 patients with advanced
      emphysema performed single-breath washouts in right and left lateral decubitus;
      nitrogen slope was measured between 75 and 100% of expired volume. In 10
      transplant recipients, the volume of each lung was measured in the two postures
      by computerized tomography. Nitrogen slope was unaffected by posture in normal
      controls and emphysema patients. On the other hand, nitrogen slope in transplant
      recipients was invariably smaller, with the graft in nondependent vs. in
      dependent position. Values of nitrogen slope with the graft in nondependent
      position were similar to those obtained in normal controls but significantly
      smaller than those obtained in emphysema patients. Computerized tomography
      studies in this position indicated that the volume expired below functional
      residual capacity was exclusively contributed by the graft. We conclude that, in
      patients with single-lung transplantation for emphysema, 1) measuring nitrogen
      slope in lateral decubitus allows to distinguish between the graft and the native
      lung, and 2) nitrogen slope obtained with the graft in nondependent position
      reflects ventilation distribution in this lung.

PMID- 16306252
TI  - Heart rate variability and cardiac reflexes in small for gestational age infants.
AB  - To assess the influence of intrauterine growth retardation and postnatal
      development on heart rate variability (HRV) and cardiac reflexes, we studied 27
      healthy small for gestational age (SGA) and 23 appropriate for gestational age
      (AGA) infants during a nap study. Resting HRV was assessed by point dispersion of
      Poincare plots for overall (SDRR) and instantaneous beat-to-beat variability
      (SDDeltaRR) and the ratio (SDRR/SDDeltaRR). Heart rate reflex and arousal
      responses to a 60 degrees head-up tilt were determined. All tests/measures were
      repeated twice in quiet and active sleep and in prone and supine sleep positions
      at 1 and 3 mo of age. SGA infants exhibited higher resting sympathetic tone
      [SDRR/SDDeltaRR: 1.9 (95% confidence interval: 1.7, 2.0) and 1.7 (95% confidence
      interval: 1.5, 1.8) in SGA and AGA, respectively; P=0.046] and a tendency for a
      smaller tachycardic reflex response to the tilt [Deltaheart rate: 24 beats/min
      (95% confidence interval: 20, 28) and 30 (95% confidence interval: 25, 34)] in
      SGA and AGA, respectively; P=0.06]. HRV indexes were reduced in the prone
      compared with supine position (P<0.0001), but reflex tilt responses were
      unchanged with position. SGA/AGA differences were independent of sleep position.
      Gestational age weight status did not influence the likelihood of arousal, but
      prone sleeping per se reduced the odds 2.5-fold. The findings suggest reduced
      autonomic activity and cardiac reflexes in SGA infants. The finding that the
      sympathetic component of the control of HRV was higher in SGA infants could link
      with findings in adulthood of an association between being born SGA and a higher
      risk of cardiovascular disease.

PMID- 16306253
TI  - Spinal estrogen attenuates the exercise pressor reflex but has little effect on
      the expression of genes regulating neurotransmitters in the dorsal root ganglia.
AB  - Previously, our laboratory showed that estrogen, topically applied to the spinal
      cord, attenuated the exercise pressor reflex in female cats (Schmitt PM and
      Kaufman MP. J Appl Physiol 95: 1418-1424, 2003; 98: 633-639, 2005). The
      attenuation was gender specific and was in part opioid dependent. Our finding
      that the mu- and delta-opioid antagonist naloxone was only able to partially
      restore estrogen's attenuating effect on the pressor response to static
      contraction suggested that estrogen affected an additional pathway, involving the
      dorsal root ganglion (DRG). Estrogen has been described to stimulate
      transcription within 10 min of its application to the DRG, raising the
      possibility that rapid genomic effects on neurotransmitter production may have
      contributed to estrogen's effect on the exercise pressor reflex. This prompted us
      to test the hypothesis that estrogen modulated the pressor response to static
      contraction by influencing gene expression of the neurotransmitters released by
      the thin-fiber muscle afferents that evoke the exercise pressor reflex. We
      confirmed in decerebrated female rats that topical application of estrogen (0.01
      microg/ml) to the lumbosacral spinal cord attenuated the pressor response to
      static muscle contraction (from 10+/-3 to 1+/-1 mmHg; P<0.05). DRG were then
      harvested postmortem, and changes in mRNA expression were analyzed. GeneChip
      analysis revealed that neither estrogen nor contraction alone changed the mRNA
      expression of substance P, the neurokinin-1 receptor, CGRP, NGF, the P2X3
      receptor, GABAA and GABAB, the 5-HT3A and 5-HT3B receptor, N-methyl-D-aspartate
      and non-N-methyl-D-aspartate receptors, opioid receptors, and opioid-like
      receptor. Surprisingly, however, contraction stimulated the expression of
      neuropeptide Y in the DRG in the presence and absence of estrogen. We conclude
      that estrogen does not attenuate the exercise pressor reflex through a genomic
      effect in the DRG.

PMID- 16306254
TI  - Cardiorespiratory responses to physical work during and following 17 days of bed
      rest and spaceflight.
AB  - To determine the influence of a 17-day exposure to real and simulated spaceflight
      (SF) on cardiorespiratory function during exercise, four male crewmembers of the
      STS-78 space shuttle flight and eight male volunteers were studied before,
      during, and after the 17-day mission and 17 days of -6 degrees head-down-tilt bed
      rest (BR), respectively. Measurements of oxygen uptake, pulmonary ventilation,
      and heart rate were made during submaximal cycling 60, 30, and 15 days before the
      SF liftoff and 12 and 7 days before BR; on SF days 2, 8, and 13 and on BR days 2,
      8, and 13; and on days 1, 4, 5, and 8 after return to Earth and on days 3 and 7
      after BR. During 15 days before liftoff, day 4 after return, and day 8 after
      return and all BR testing, each subject completed a continuous exercise test to
      volitional exhaustion on a semirecumbent (SF) or supine (BR) cycle ergometer to
      determine the submaximal and maximal cardiorespiratory responses to exercise. The
      remaining days of the SF testing were limited to a workload corresponding to 85%
      of the peak pre-SF peak oxygen uptake (Vo2 peak) workload. Exposure to and
      recovery from SF and BR induced similar responses to submaximal exercise at 150
      W. Vo2 peak decreased by 10.4% from pre-SF (15 days before liftoff) to day 4
      after return and 6.6% from pre-BR to day 3 after return, which was partially (SF:
      -5.2%) or fully (BR) restored within 1 wk of recovery. Workload corresponding to
      85% of the peak pre-SF Vo2 peak showed a rapid and continued decline throughout
      the flight (SF day 2, -6.2%; SF day 8, -9.0%), reaching a nadir of -11.3% during
      testing on SF day 13. During BR, Vo2 peak also showed a decline from pre-BR (BR
      day 2, -7.3%; BR day 8, -7.1%; BR day 13, -9.0%). These results suggest that the
      onset of and recovery from real and simulated microgravity-induced
      cardiorespiratory deconditioning is relatively rapid, and head-down-tilt BR
      appears to be an appropriate model of this effect, both during and after SF.

PMID- 16306255
TI  - Predicting human chronically paralyzed muscle force: a comparison of three
      mathematical models.
AB  - Chronic spinal cord injury (SCI) induces detrimental musculoskeletal adaptations
      that adversely affect health status, ranging from muscle paralysis and skin
      ulcerations to osteoporosis. SCI rehabilitative efforts may increasingly focus on
      preserving the integrity of paralyzed extremities to maximize health quality
      using electrical stimulation for isometric training and/or functional activities.
      Subject-specific mathematical muscle models could prove valuable for predicting
      the forces necessary to achieve therapeutic loading conditions in individuals
      with paralyzed limbs. Although numerous muscle models are available, three
      modeling approaches were chosen that can accommodate a variety of stimulation
      input patterns. To our knowledge, no direct comparisons between models using
      paralyzed muscle have been reported. The three models include 1) a simple second
      order linear model with three parameters and 2) two six-parameter nonlinear
      models (a second-order nonlinear model and a Hill-derived nonlinear model).
      Soleus muscle forces from four individuals with complete, chronic SCI were used
      to optimize each model's parameters (using an increasing and decreasing frequency
      ramp) and to assess the models' predictive accuracies for constant and variable
      (doublet) stimulation trains at 5, 10, and 20 Hz in each individual. Despite the
      large differences in modeling approaches, the mean predicted force errors
      differed only moderately (8-15% error; P=0.0042), suggesting physiological force
      can be adequately represented by multiple mathematical constructs. The two
      nonlinear models predicted specific force characteristics better than the linear
      model in nearly all stimulation conditions, with minimal differences between the
      two nonlinear models. Either nonlinear mathematical model can provide reasonable
      force estimates; individual application needs may dictate the preferred modeling
      strategy.

PMID- 16306256
TI  - Volume-related and volume-independent effects of posture on esophageal and
      transpulmonary pressures in healthy subjects.
AB  - Ventilator management decisions in acute lung injury could be better informed
      with knowledge of the patient's transpulmonary pressure, which can be estimated
      using measurements of esophageal pressure. Esophageal manometry is seldom used
      for this, however, in part because of a presumed postural artifact in the supine
      position. Here, we characterize the magnitude and variability of postural effects
      on esophageal pressure in healthy subjects to better assess its significance in
      patients with acute lung injury. We measured the posture-related changes in
      relaxation volume and total lung capacity in 10 healthy subjects in four
      postures: upright, supine, prone, and left lateral decubitus. Then, in the same
      subjects, we measured static pressure-volume characteristics of the lung over a
      wide range of lung volumes in each posture by using an esophageal balloon
      catheter. Transpulmonary pressure during relaxation (PLrel) averaged 3.7 (SD 2.0)
      cmH2O upright and -3.3 (SD 3.2) cmH2O supine. Approximately 58% of the decrease
      in PLrel between the upright and supine postures was due to a corresponding
      decrease in relaxation volume. The remaining 2.9-cmH2O difference is consistent
      with reported values of a presumed postural artifact. Relaxation volumes and
      pressures in prone and lateral postures were intermediate. To correct estimated
      transpulmonary pressure for the effect of lying supine, we suggest adding 3 cmH2O
      (95% confidence interval: -1 to +7 cmH2O). We conclude that postural differences
      in estimated transpulmonary pressure at a given lung volume are small compared
      with the substantial range of PLrel in patients with acute lung injury.

PMID- 16306257
TI  - Optimization of oxygen tolerance extension in rats by intermittent exposure.
AB  - Optimization of oxygen tolerance extension by intermittent exposure was studied
      in groups of 20 rats exposed to systematically varied patterns of alternating
      oxygen and normoxic breathing periods at 4.0, 2.0, and 1.5 ATA. Oxygen periods of
      20, 60, and 120 min were alternated with normoxic intervals that provided oxygen
      to-normoxia ratios of 4:1, 2:1, 1:1, and 1:3. In general, median survival times
      had nearly linear relationships to increasing normoxic intervals with oxygen
      period held constant. Exceptions occurred at 4.0 and 2.0 ATA where a 5-min
      normoxic interval was too short for adequate recovery even with a 20-min oxygen
      period, and an oxygen period of 120 min was too long even with a normoxic
      interval of 30 min. These exceptions did not occur at 1.5 ATA. Survival time for
      many intermittent exposure patterns was equivalent to that for continuous
      exposure to an oxygen pressure definable as a time-weighted average of the
      alternating oxygen and normoxia periods. However, this predictive method
      underestimated the degree of protection achieved by several of the intermittent
      exposure patterns, especially those performed at 4.0 ATA. Results provided
      guidance for selection of intermittent exposure patterns for direct evaluation in
      humans breathing oxygen at 2.0 ATA. Definition of intermittent exposure patterns
      and conditions that produced prominent gains in oxygen tolerance can also
      facilitate the performance of future experiments designed to study potential
      mechanisms for oxygen tolerance extension by intermittent exposure. Heat shock
      and oxidation-specific stress proteins that are induced by exposure to oxidant
      injury are suggested for emphasis in such investigations.

PMID- 16306258
TI  - Gene expression profiling differentiates germ cell tumors from other cancers and
      defines subtype-specific signatures.
AB  - Germ cell tumors (GCTs) of the testis are the predominant cancer among young men.
      We analyzed gene expression profiles of 50 GCTs of various subtypes, and we
      compared them with 443 other common malignant tumors of epithelial, mesenchymal,
      and lymphoid origins. Significant differences in gene expression were found among
      major histological subtypes of GCTs, and between them and other malignancies. We
      identified 511 genes, belonging to several critical functional groups such as
      cell cycle progression, cell proliferation, and apoptosis, to be significantly
      differentially expressed in GCTs compared with other tumor types. Sixty-five
      genes were sufficient for the construction of a GCT class predictor of high
      predictive accuracy (100% training set, 96% test set), which might be useful in
      the diagnosis of tumors of unknown primary origin. Previously described
      diagnostic and prognostic markers were found to be expressed by the appropriate
      GCT subtype (AFP, POU5F1, POV1, CCND2, and KIT). Several additional
      differentially expressed genes were identified in teratomas (EGR1 and MMP7), yolk
      sac tumors (PTPN13 and FN1), and seminomas (NR6A1, DPPA4, and IRX1). Dynamic
      computation of interaction networks and mapping to existing pathways knowledge
      databases revealed a potential role of EGR1 in p21-induced cell cycle arrest and
      intrinsic chemotherapy resistance of mature teratomas.

PMID- 16306259
TI  - Fast noninvasive activation and inhibition of neural and network activity by
      vertebrate rhodopsin and green algae channelrhodopsin.
AB  - Techniques for fast noninvasive control of neuronal excitability will be of major
      importance for analyzing and understanding neuronal networks and animal behavior.
      To develop these tools we demonstrated that two light-activated signaling
      proteins, vertebrate rat rhodopsin 4 (RO4) and the green algae channelrhodospin 2
      (ChR2), could be used to control neuronal excitability and modulate synaptic
      transmission. Vertebrate rhodopsin couples to the Gi/o, pertussis toxin-sensitive
      pathway to allow modulation of G protein-gated inward rectifying potassium
      channels and voltage-gated Ca2+ channels. Light-mediated activation of RO4 in
      cultured hippocampal neurons reduces neuronal firing within ms by
      hyperpolarization of the somato-dendritic membrane and when activated at
      presynaptic sites modulates synaptic transmission and paired-pulse facilitation.
      In contrast, somato-dendritic activation of ChR2 depolarizes neurons sufficiently
      to induce immediate action potentials, which precisely follow the ChR2 activation
      up to light stimulation frequencies of 20 Hz. To demonstrate that these
      constructs are useful for regulating network behavior in intact organisms,
      embryonic chick spinal cords were electroporated with either construct, allowing
      the frequency of episodes of spontaneous bursting activity, known to be important
      for motor circuit formation, to be precisely controlled. Thus light-activated
      vertebrate RO4 and green algae ChR2 allow the antagonistic control of neuronal
      function within ms to s in a precise, reversible, and noninvasive manner in
      cultured neurons and intact vertebrate spinal cords.

PMID- 16306260
TI  - Simple model for tuberculosis in cattle and badgers.
AB  - As an aid to the study of bovine tuberculosis (TB), a simple model has been
      developed of an epidemic involving two species, cattle and badgers. Each species
      may infect the other. The proportion of animals affected is assumed relatively
      small so that the usual nonlinear aspects of epidemic theory are avoided. The
      model is used to study the long-run and transient effect on cattle of culling
      badgers and the effect of a period without routine testing for TB, such as
      occurred during the 2001 epidemic of foot-and-mouth disease in Great Britain.
      Finally, by examining the changes in cattle TB over the last 15 years, and with
      some other working assumptions, it is estimated that the net reproduction number
      of the epidemic is approximately 1.1. The implications for controlling the
      disease are discussed.

PMID- 16306261
TI  - Dynamics of hepatitis B virus clearance in chimpanzees.
AB  - Mathematical modeling was performed to test the extent to which cytopathic and
      noncytopathic T cell effector functions contribute to resolution of hepatitis B
      virus (HBV) infection in three acutely infected chimpanzees. Simulations based
      exclusively on cytopathic functions show a poor fit to the data and would require
      the destruction and regeneration of approximately 11 livers for clearance to
      occur. In contrast, a simulation based on a combination of cytopathic and
      noncytopathic functions provided a significantly better fit to the data (P <
      0.001) and required as much as 5-fold less destruction to clear the virus from
      the liver. The best fit simulation supports the notion that during the early
      phase of HBV clearance, noncytopathic T cell effector mechanisms inhibit viral
      replication and greatly shorten the half-life of the long lived covalently closed
      circular viral DNA transcriptional template, thereby limiting the extent to which
      cytopathic T cell effector functions and tissue destruction are required to
      terminate acute HBV infection.

PMID- 16306262
TI  - Crystal structure of Bacillus subtilis anti-TRAP protein, an antagonist of
      TRAP/RNA interaction.
AB  - In Bacillus subtilis the anti-TRAP protein (AT) is produced in response to the
      accumulation of uncharged tRNA(Trp). AT regulates expression of genes involved in
      tryptophan biosynthesis and transport by binding to the tryptophan-activated trp
      RNA-binding attenuation protein (TRAP) and preventing its interaction with
      several mRNAs. Here, we report the x-ray structure of AT at 2.8 angstroms
      resolution, showing that the protein subunits assemble into tight trimers. Four
      such trimers are further associated into a 12-subunit particle in which
      individual trimers are related by twofold and threefold symmetry axes. Twelve
      DnaJ-like, cysteine-rich zinc-binding domains form spikes on the surface of the
      dodecamer. Available data suggest several possible ways for AT to interact with
      the 11-subunit TRAP. Interaction between the two symmetry-mismatching molecules
      could be assisted by the flexible nature of AT zinc-binding domains.

PMID- 16306263
TI  - Rerouting lipoprotein nanoparticles to selected alternate receptors for the
      targeted delivery of cancer diagnostic and therapeutic agents.
AB  - We report that a lipoprotein-based nanoplatform generated by conjugating tumor
      homing molecules to the protein components of naturally occurring lipoproteins
      reroutes them from their normal lipoprotein receptors to other selected cancer
      associated receptors. Multiple copies of these targeting moieties may be attached
      to the same nanoparticle, or a variety of different targeting moieties can be
      attached. Such a diverse set of tumor-homing molecules could be used to create a
      variety of conjugated lipoproteins as multifunctional, biocompatible
      nanoplatforms with a broad application to both cancer imaging and treatment. The
      same principle can be applied to imaging and treatment of other diseases and for
      monitoring specific tissues. To validate this concept, we prepared a low-density
      lipoprotein (LDL)-based folate receptor (FR)-targeted agent by conjugating folic
      acid to the Lys residues of the apolipoprotein B (apoB)-100 protein. To
      demonstrate the ability of the lipoprotein-based nanoplatform to deliver surface
      loaded and core-loaded payloads, the particles were labeled either with the
      optical reporter 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine that was
      intercalated in the phospholipid monolayer or with the lipophilic photodynamic
      therapy agent, tetra-t-butyl-silicon phthalocyanine bisoleate, that was
      reconstituted into the lipid core. Cellular localization of the labeled LDL was
      monitored by confocal microscopy and flow cytometry in FR-overexpressing KB
      cells, in FR-nonexpressing CHO and HT-1080 cells, and in LDL receptor
      overexpressing HepG2 cells. These studies demonstrate that the folic acid
      conjugation to the Lys side-chain amino groups blocks binding to the normal LDL
      receptor and reroutes the resulting conjugate to cancer cells through their FRs.

PMID- 16306264
TI  - Bacterial DNA segregation by dynamic SopA polymers.
AB  - Many bacterial plasmids and chromosomes rely on ParA ATPases for proper
      positioning within the cell and for efficient segregation to daughter cells. Here
      we demonstrate that the F-plasmid-partitioning protein SopA polymerizes into
      filaments in an ATP-dependent manner in vitro, and that the filaments elongate at
      a rate that is similar to that of plasmid separation in vivo. We show that SopA
      is a dynamic protein within the cell, undergoing cycles of polymerization and
      depolymerization, and shuttling back and forth between nucleoprotein complexes
      that are composed of the SopB protein bound to sopC-containing plasmids
      (SopB/sopC). The dynamic behavior of SopA is critical for Sop-mediated plasmid
      DNA segregation; mutations that lock SopA into a static polymer in the cell
      inhibit plasmid segregation. We show that SopA colocalizes with SopB/sopC in the
      cell and that SopB/sopC nucleates the assembly of SopA and is required for its
      dynamic behavior. When SopA is polymerized in vitro in the presence of SopB and
      sopC-containing DNA, SopA filaments emanate from the plasmid DNA in radial
      asters. We propose a mechanism in which plasmid separation is driven by the
      polymerization of SopA, and we speculate that the radial assembly of SopA
      polymers is responsible for positioning plasmids both before and after
      segregation.

PMID- 16306265
TI  - Progression of primary pneumonic plague: a mouse model of infection, pathology,
      and bacterial transcriptional activity.
AB  - Although pneumonic plague is the deadliest manifestation of disease caused by the
      bacterium Yersinia pestis, there is surprisingly little information on the
      cellular and molecular mechanisms responsible for Y. pestis-triggered pathology
      in the lung. Therefore, to understand the progression of this unique disease, we
      characterized an intranasal mouse model of primary pneumonic plague. Mice
      succumbed to a purulent multifocal severe exudative bronchopneumonia that closely
      resembles the disease observed in humans. Analyses revealed a strikingly biphasic
      syndrome, in which the infection begins with an antiinflammatory state in the
      first 24-36 h that rapidly progresses to a highly proinflammatory state by 48 h
      and death by 3 days. To assess the adaptation of Y. pestis to a mammalian
      environment, we used DNA microarray technology to analyze the transcriptional
      responses of the bacteria during interaction with the mouse lung. Included among
      the genes up-regulated in vivo are those comprising the yop-ysc type III
      secretion system and genes contained within the chromosomal pigmentation locus,
      validating the use of this technology to identify loci essential to the virulence
      of Y. pestis.

PMID- 16306266
TI  - The timing of proton migration in membrane-reconstituted cytochrome c oxidase.
AB  - In mitochondria and aerobic bacteria energy conservation involves electron
      transfer through a number of membrane-bound protein complexes to O2. The
      reduction of O2, accompanied by the uptake of substrate protons to form H2O, is
      catalyzed by cytochrome c oxidase (CcO). This reaction is coupled to proton
      translocation (pumping) across the membrane such that each electron transfer to
      the catalytic site is linked to the uptake of two protons from one side and the
      release of one proton to the other side of the membrane. To address the mechanism
      of vectorial proton translocation, in this study we have investigated the solvent
      deuterium isotope effect of proton-transfer rates in CcO oriented in small
      unilamellar vesicles. Although in H2O the uptake and release reactions occur with
      the same rates, in D2O the substrate and pumped protons are taken up first
      (tau(D) congruent with 200 micros, "peroxy" to "ferryl" transition) followed by a
      significantly slower proton release to the other side of the membrane (tau(D)
      congruent with 1 ms). Thus, the results define the order and timing of the proton
      transfers during a pumping cycle. Furthermore, the results indicate that during
      CcO turnover internal electron transfer to the catalytic site is controlled by
      the release of the pumped proton, which suggests a mechanism by which CcO
      orchestrates a tight coupling between electron transfer and proton translocation.

PMID- 16306268
TI  - Brain signals for spatial attention predict performance in a motion
      discrimination task.
AB  - The reliability of visual perception is thought to reflect the quality of the
      sensory information. However, we show that subjects' performance can be
      predicted, trial-by-trial, by neural activity that precedes the onset of a
      sensory stimulus. Using functional MRI (fMRI), we studied how neural mechanisms
      that mediate spatial attention affect the accuracy of a motion discrimination
      judgment. The amplitude of blood oxygen level-dependent (BOLD) signals after a
      cue directing spatial attention predicted subjects' accuracy on 60-75% of the
      trials. Widespread predictive signals, which included dorsal parietal, visual
      extra-striate, prefrontal and sensory-motor cortex, depended on whether the cue
      correctly specified the stimulus location. Therefore, these signals indicate the
      degree of utilization of the cued information and play a role in the control of
      spatial attention. We conclude that variability in perceptual performance can be
      partly explained by the variability in endogenous, preparatory processes and that
      BOLD signals can be used to forecast human behavior.

PMID- 16306267
TI  - A cysteine-rich motif confers hypoxia sensitivity to mammalian large conductance
      voltage- and Ca-activated K (BK) channel alpha-subunits.
AB  - Cellular responses to hypoxia are tissue-specific and dynamic. However, the
      mechanisms that underlie this differential sensitivity to hypoxia are unknown.
      Large conductance voltage- and Ca-activated K (BK) channels are important
      mediators of hypoxia responses in many systems. Although BK channels are
      ubiquitously expressed, alternative pre-mRNA splicing of the single gene encoding
      their pore-forming alpha-subunits provides a powerful mechanism for generating
      functional diversity. Here, we demonstrate that the hypoxia sensitivity of BK
      channel alpha-subunits is splice-variant-specific. Sensitivity to hypoxia is
      conferred by a highly conserved motif within an alternatively spliced cysteine
      rich insert, the stress-regulated exon (STREX), within the intracellular C
      terminus of the channel. Hypoxic inhibition of the STREX variant is Ca-sensitive
      and reversible, and it rapidly follows the change in oxygen tension by means of a
      mechanism that is independent of redox or CO regulation. Hypoxia sensitivity was
      abolished by mutation of the serine (S24) residue within the STREX insert.
      Because STREX splice-variant expression is tissue-specific and dynamically
      controlled, alternative splicing of BK channels provides a mechanism to control
      the plasticity of cellular responses to hypoxia.

PMID- 16306269
TI  - Salmonella inhibit T cell proliferation by a direct, contact-dependent
      immunosuppressive effect.
AB  - Dendritic cells (DC) are of central importance in the initiation of T cell
      mediated adaptive immunity because these professional phagocytes internalize,
      process, and present microbial antigens to T lymphocytes. T lymphocytes have a
      pivotal role in controlling and clearing infection with intracellular pathogens
      through cytokine production. T lymphocytes also can mediate direct lysis of
      infected cells or activate B and T cells. In this article, we report that DC,
      when cocultured with Salmonella, fail to efficiently stimulate T cells for
      proliferation. We show that the failure of T lymphocytes to respond to Salmonella
      infected DC is not simply due to Salmonella-induced programmed DC death or
      interference with up-regulation of costimulatory molecules CD80 and CD86. We
      cocultured bacteria with purified T lymphocytes, and we demonstrate here that
      Salmonella have a direct, contact-dependent inhibitory effect on the T cells,
      even in the absence of DC. This direct, Salmonella-induced inhibitory effect
      reduces the ability of T cells to proliferate and produce cytokines in response
      to stimulation and appears to require live bacteria. Cumulatively, these results
      are evidence that Salmonella may interfere with the development of acquired
      immunity, providing insights into the complex nature of this host-pathogen
      interaction.

PMID- 16306270
TI  - Coupled protein domain motion in Taq polymerase revealed by neutron spin-echo
      spectroscopy.
AB  - Long-range conformational changes in proteins are ubiquitous in biology for the
      transmission and amplification of signals; such conformational changes can be
      triggered by small-amplitude, nanosecond protein domain motion. Understanding how
      conformational changes are initiated requires the characterization of protein
      domain motion on these timescales and on length scales comparable to protein
      dimensions. Using neutron spin-echo spectroscopy (NSE), normal mode analysis, and
      a statistical-mechanical framework, we reveal overdamped, coupled domain motion
      within DNA polymerase I from Thermus aquaticus (Taq polymerase). This protein
      utilizes correlated domain dynamics over 70 angstroms to coordinate nucleotide
      synthesis and cleavage during DNA synthesis and repair. We show that NSE
      spectroscopy can determine the domain mobility tensor, which determines the
      degree of dynamical coupling between domains. The mobility tensor defines the
      domain velocity response to a force applied to it or to another domain, just as
      the sails of a sailboat determine its velocity given the applied wind force. The
      NSE results provide insights into the nature of protein domain motion that are
      not appreciated by conventional biophysical techniques.

PMID- 16306272
TI  - Glibenclamide-induced apoptosis is specifically enhanced by expression of the
      sulfonylurea receptor isoform SUR1 but not by expression of SUR2B or the mutant
      SUR1(M1289T).
AB  - Sulfonylurea receptor 1 (SUR1) is the regulatory subunit of the pancreatic ATP
      sensitive K+ channel (K(ATP) channel), which is essential for triggering insulin
      secretion via membrane depolarization. Sulfonylureas, such as glibenclamide and
      tolbutamide, act as K(ATP) channel blockers and are widely used in diabetes
      treatment. These antidiabetic substances are known to induce apoptosis in
      pancreatic beta-cells or beta-cell lines under certain conditions. However, the
      precise molecular mechanisms of this sulfonylurea-induced apoptosis are still
      unidentified. To investigate the role of SUR in apoptosis induction, we tested
      the effect of glibenclamide on recombinant human embryonic kidney 293 cells
      expressing either SUR1, the smooth muscular isoform SUR2B, or the mutant
      SUR1(M1289T) at which a single amino acid in transmembrane helix 17 (TM17) was
      exchanged by the corresponding amino acid of SUR2. By analyzing cell detachment,
      nuclear condensation, DNA fragmentation, and caspase-3-like activity, we observed
      a SUR1-specific enhancement of glibenclamide-induced apoptosis that was not seen
      in SUR2B, SUR1(M1289T), or control cells. Coexpression with the pore-forming
      Kir6.2 subunit did not significantly alter the apoptotic effect of glibenclamide
      on SUR1 cells. In conclusion, expression of SUR1, but not of SUR2B or
      SUR1(M1289T), renders cells more susceptible to glibenclamide-induced apoptosis.
      Therefore, SUR1 as a pancreatic protein could be involved in specific variation
      of beta-cell mass and might also contribute to the regulation of insulin
      secretion at this level. According to our results, TM17 is essentially involved
      in SUR1-mediated apoptosis. This effect does not require the presence of
      functional Kir6.2-containing K(ATP) channels, which points to additional, so far
      unknown functions of SUR.

PMID- 16306271
TI  - Perfusion functional MRI reveals cerebral blood flow pattern under psychological
      stress.
AB  - Despite the prevalence of stress in everyday life and its impact on happiness,
      health, and cognition, little is known about the neural substrate of the
      experience of everyday stress in humans. We use a quantitative and noninvasive
      neuroimaging technique, arterial spin-labeling perfusion MRI, to measure cerebral
      blood flow (CBF) changes associated with mild to moderate stress induced by a
      mental arithmetic task with performance monitoring. Elicitation of stress was
      verified by self-report of stress and emotional state and measures of heart rate
      and salivary-cortisol level. The change in CBF induced by the stress task was
      positively correlated with subjective stress rating in the ventral right
      prefrontal cortex (RPFC) and left insula/putamen area. The ventral RPFC along
      with right insula/putamen and anterior cingulate showed sustained activation
      after task completion in subjects reporting a high stress level during arithmetic
      tasks. Additionally, variations of baseline CBF in the ventral RPFC and right
      orbitofrontal cortex were found to correlate with changes in salivary-cortisol
      level and heart rate caused by undergoing stress tasks. We further demonstrated
      that the observed right prefrontal activation could not be attributed to
      increased cognitive demand accompanying stress tasks and extended beyond neural
      pathways associated with negative emotions. Our results provide neuroimaging
      evidence that psychological stress induces negative emotion and vigilance and
      that the ventral RPFC plays a key role in the central stress response.

PMID- 16306273
TI  - Erythropoietin, modified to not stimulate red blood cell production, retains its
      cardioprotective properties.
AB  - Erythropoietin (EPO), a hematopoietic cytokine, possesses strong antiapoptotic,
      tissue-protective properties. For clinical applications, it is desirable to
      separate the hematopoietic and tissue-protective properties. Recently introduced
      carbamylated erythropoietin (CEPO) does not stimulate the erythropoiesis but
      retains the antiapoptotic and neuroprotective effects. We tested the ability of
      CEPO to protect cardiac tissue from toxin-induced and oxidative stress in vitro
      and ischemic damage in vivo and compared these effects with the effects of EPO.
      CEPO reduced by 50% the extent of staurosporine-induced apoptosis in isolated
      rats' cardiomyocytes and increased by 25% the reactive oxygen species threshold
      for induction of the mitochondrial permeability transition. In an experimental
      model of myocardial infarction induced by permanent ligation of a coronary artery
      in rats, similarly to EPO, a single bolus injection of 30 mug/kg b.wt. of CEPO
      immediately after coronary ligation reduced apoptosis in the myocardial area at
      risk, examined 24 h later, by 50%. Left ventricular remodeling (ventricular
      dilation) and functional decline (fall in ejection fraction) assessed by repeated
      echocardiography were significantly and similarly attenuated in CEPO- and EPO
      treated rats. Four weeks after coronary ligation, the myocardial infarction (MI)
      size in CEPO- and EPO-treated rats was half of that in untreated coronary-ligated
      animals. Unlike EPO, CEPO had no effect on hematocrit. The antiapoptotic
      cardioprotective effects of CEPO, shown by its ability to limit both post-MI left
      ventricular remodeling and the extent of the myocardial scar in the model of
      permanent coronary artery ligation in rats, demonstrate comparable potency to
      that of native (nonmodified) EPO.

PMID- 16306274
TI  - Opposite effects of pre- and postischemic treatments with nitric oxide donor on
      ischemia/reperfusion-induced renal injury.
AB  - We have demonstrated previously that preischemic treatment with FK409 [(+/-)-(E)
      4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide], a spontaneous nitric oxide
      (NO) donor, markedly improves ischemia/reperfusion-induced renal injury. However,
      there is conflicting information (renoprotective or cytotoxic) as to the
      contribution of NO to ischemic acute renal failure (ARF). In the present study,
      we investigated the effect of postischemic treatment with FK409 (1, 3, and 10
      mg/kg i.v.) at 6 h after reperfusion on ischemic ARF, in comparison with the
      preischemic treatment effect. Ischemic ARF was induced by clamping of the left
      renal artery and vein for 45 min, followed by reperfusion, 2 weeks after
      contralateral nephrectomy. Renal function in ARF rats markedly decreased at 24 h
      after reperfusion. Histopathological examination of the kidney of ARF rats
      revealed severe renal damage. In contrast to the renoprotective effect by
      preischemic treatment, postischemic treatment with FK409 aggravated the
      ischemia/reperfusion-induced renal dysfunction and histological damage.
      Immunohistochemical analysis of renal sections obtained from ARF rats revealed
      positive staining for nitrotyrosine, a biomarker of peroxynitrite formation, in
      injured tubular cells, and more intense staining was observed in renal tissues
      from the animals that received postischemic treatment with FK409. On the other
      hand, the formation of nitrotyrosine, neutrophil infiltration into renal tissues,
      and renal superoxide production, all of which were enhanced in ARF rats, were
      efficiently attenuated by the preischemic treatment with FK409. These results
      demonstrate that, although preischemic treatment with an NO donor is
      renoprotective, postischemic treatment with the same agent aggravates the
      ischemia/reperfusion-induced renal injury, probably through peroxynitrite
      overproduction.

PMID- 16306275
TI  - What does it mean to be a physician?

PMID- 16306276
TI  - Emerging and reemerging infectious diseases: the perpetual challenge.
AB  - Public health officials once suggested that it might someday be possible to
      "close the book" on the study and treatment of infectious diseases. However, it
      is now clear that endemic diseases as well as newly emerging ones (e.g., severe
      acute respiratory syndrome [SARS]), reemerging ones (e.g., West Nile virus), and
      even deliberately disseminated infectious diseases (e.g., anthrax from
      bioterrorism) continue to pose a substantial threat throughout the world. Over
      the past several decades, the global effort to identify and characterize
      infectious agents, decipher the underlying pathways by which they cause disease,
      and develop preventive measures and treatments for many of the world's most
      dangerous pathogens has helped control many endemic diseases. But despite
      considerable progress, infectious diseases continue to present significant
      challenges as new microbial threats emerge and reemerge. HIV/AIDS, malaria,
      tuberculosis, influenza, SARS, West Nile virus, Marburg virus, and bioterrorism
      are examples of some of the emerging and reemerging threats. In responding to
      these ongoing challenges, a new paradigm in countermeasure development is needed.
      In the past, U.S. government-sponsored biomedical researchers have focused on
      basic research and concept development, leaving product development to the
      pharmaceutical industry. Increasingly, however, the government has become
      involved in more targeted countermeasure development efforts. In this regard,
      partnerships between government, industry, and academia are necessary as we
      struggle to maintain and update our armamentarium in the struggle to outwit the
      microbes that pose a never-ending threat to mankind.

PMID- 16306277
TI  - Viewpoint: New physicians for a new century.
AB  - How to train competent and compassionate physicians has assumed a new urgency.
      The authors propose that these concerns be approached by radically restructuring
      the medical school curriculum in ways that place facts and skills within the
      context of ethics and values. Doing so will require that the positivist stance of
      medical education be coupled to strategies that deal with ambiguity and
      uncertainty, communication and empathy, and, most important, physician self
      awareness. Achieving such balance will require fundamental change in medicine's
      education philosophy along five general lines: (1) assertion of medical ethics as
      the foundation of clinical medicine; (2) recognition of the central place of
      values in clinical decision making; (3) cultivation of the ethos of humane care;
      (4) selection of medical students with the dual capacities of strong cognitive
      skills and empathy; and (5) encouragement and support of faculty who can transmit
      the knowledge of clinical science coupled to the principles of humane care. Such
      changes are both timely and necessary. Although they will be difficult to
      accomplish, they offer an opportunity for medical educators to foster the
      development of physicians with the range attributes that this new century
      demands.

PMID- 16306278
TI  - Viewpoint: Improving the health of the public requires changes in medical
      education.
AB  - It has been widely accepted and recommended that the needed improvements in the
      quality of health care require fundamental reforms in medical education. However,
      it is essential to recognize that there are significant problems not only with
      the quality but also with the quantity of health care in the United States. The
      medical profession has to confront the fundamental moral problem of unrealized
      rights and unattained justice in health care that has resulted in explicit harm
      to the health of a large portion of the population. Does this state of affairs
      have anything to do with the ways physicians have been educated about civic
      responsibilities, leadership, and professional integrity? What kind of education
      is to be provided for what kind of physicians and for what kind of medicine?
      Emphasis should be placed on the leadership role and on the underlying attitudes
      and values of physicians that reflect the morality of medicine. The doctor
      patient and doctor-society relationships are part and parcel of the moral and
      professional responsibilities of physicians. Different moralities are involved
      when medicine is practiced as a job or business or vocation, because these entail
      different dispositions toward patients and society. The envisioned educational
      changes should challenge and prepare physicians not only with regard to their
      knowledge and skills but also with regard to their moral and professional
      integrity and leadership, so they may serve individuals and society in a health
      care system that ensures equal access to high-quality services for all.

PMID- 16306279
TI  - Lost in translation: challenges and opportunities in physician-to-physician
      communication during patient handoffs.
AB  - Handoffs involve the transfer of rights, duties, and obligations from one person
      or team to another. In many high-precision, high-risk contexts such as a relay
      race or handling air traffic, handoff skills are practiced repetitively to
      optimize precision and anticipate errors. In medicine, wide variation exists in
      handoffs of hospitalized patients from one physician or team to another.
      Effective information transfer requires a solid foundation in communication
      skills. While these skills have received much attention in the medical
      literature, scholarship has focused on physician-to-patient, not physician-to
      physician, communication. Little formal attention or education is available to
      reinforce this vital link in the continuity of patient care. The authors reviewed
      the literature on patient handoffs and evaluated the patient handoff process at
      Indiana University School of Medicine's internal medicine residency. House
      officers there rotate through four hospitals with three different computer
      systems. Two of the hospitals employ a computer-assisted patient handoff system;
      the other two utilize the standard pen-to-paper method. Considerable variation
      was observed in the quality and content of handoffs across these settings. Four
      major barriers to effective handoffs were identified: (1) the physical setting,
      (2) the social setting, (3) language barriers, and 4) communication barriers. The
      authors conclude that irrespective of local context, precise, unambiguous, face
      to-face communication is the best way to ensure effective handoffs of
      hospitalized patients. They also maintain that the handoff process must be
      standardized and that students and residents must be taught the most effective,
      safe, satisfying, and efficient ways to perform handoffs.

PMID- 16306280
TI  - Aligning compensation with education: design and implementation of the
      Educational Value Unit (EVU) system in an academic internal medicine department.
AB  - The authors report the development of a new metric for distributing university
      funds to support faculty efforts in education in the department of internal
      medicine at the University of Kansas School of Medicine. In 2003, a committee
      defined the educational value unit (EVU), which describes and measures the
      specific types of educational work done by faculty members, such as core
      education, clinical teaching, and administration of educational programs. The
      specific work profile of each faculty member was delineated. A dollar value was
      calculated for each 0.1 EVU. The metric was prospectively applied and a faculty
      survey was performed to evaluate the faculty's perception of the metric.
      Application of the metric resulted in a decrease in university support for 34
      faculty and an increase in funding for 23 faculty. Total realignment of funding
      was US$1.6 million, or an absolute value of US$29,072 +/- 38,320.00 in average
      shift of university salary support per faculty member. Survey results showed that
      understanding of the purpose of university funding was enhanced, and that faculty
      members perceived a more equitable alignment of teaching effort with funding. The
      EVU metric resulted in a dramatic realignment of university funding for
      educational efforts in the department of internal medicine. The metric was easily
      understood, quickly implemented, and perceived to be fair by the faculty. By
      aligning specific salary support with faculty's educational responsibilities, a
      foundation was created for applying mission-based incentive programs.

PMID- 16306281
TI  - Teaching and learning moments: Turning tables.

PMID- 16306282
TI  - Using the PRACTICE mnemonic to apply cultural competency to genetics in medical
      education and patient care.
AB  - Medical education curricula increasingly are incorporating courses on cultural
      competency and skills development in working with ethnically diverse patient
      populations as well as courses on genetics and genomics. The authors support
      these efforts and believe the next step is integration of genetics into cultural
      competency programs and similarly, cultural competency into genetics curricula.
      In this paper, the authors describe the work of the Genetics in Primary Care
      Faculty Development Working Group on Cultural Competency, a federally-funded
      initiative to prepare generalist faculty to teach genetics as part of ambulatory
      education. Over a 12-month period, this team wrote a module on cultural
      competency and nine new clinical cases, and developed the PRACTICE mnemonic
      (prevalence, risk, attitude, communication, testing, investigation, consent,
      empowerment) to help health care professionals integrate cultural competency
      skills in genetics into primary care. More specifically, the PRACTICE mnemonic
      integrates information emerging from experts in health disparities and doctor
      patient communication to build a comprehensive model for addressing the relevance
      of culture and ethnicity in the delivery of genetic services. Lastly, this paper
      illustrates a systematic method of covering key areas of cultural competency
      through discussion of a patient with a genetic disorder as well as presents an
      argument as to why cultural competency is highly relevant to the delivery of
      genetic services especially as part of generalists' clinical practice.

PMID- 16306283
TI  - Teaching and learning moments: Anaphylactic shock.

PMID- 16306284
TI  - Using children as simulated patients in communication training for residents and
      medical students: a pilot program.
AB  - Medical schools are charged with the challenge of teaching effective
      communication skills, a core competency for residents and medical students.
      Especially challenging is the task of developing effective methods for training
      residents and students to communicate with children with mental health issues.
      The authors describe a pilot program at Mercer University School of Medicine that
      used pediatric standardized patients (SPs), ages 9-19, to aid in training
      residents and medical students in complex interviewing skills addressing mental
      health issues. New curriculum components for four pediatric problems, anorexia
      nervosa, depression, separation anxiety, and attention deficit hyperactivity
      disorder (ADHD), were designed and implemented by the authors in 2002-04. The
      training sessions were evaluated by the participating SPs as well as the
      residents and medical students in training. The components of the training were a
      lecture and subsequent practice using pediatric SPs and adults acting as their
      mothers. Evaluation included the qualitative analysis of SPs' reactions to
      participation in the training as described during a posttraining-session focus
      group, as well as questionnaire responses by residents and medical students. The
      children role-playing the scenario of a difficult-to-manage situation and their
      adult "parent" actors voiced strongly positive reactions to participating in
      training residents and medical students. The reactions of physicians in training
      were also positive. The authors thus conclude that child and adolescent actors
      can be effectively used as SPs to train residents and students in complex
      interviewing skills, even in cases involving children with challenging mental
      health issues.

PMID- 16306285
TI  - Viewpoint: suggestions for a shift in teaching clinical skills to medical
      students: the reflective clinical examination.
AB  - How medical students are taught physical examination (PE) skills appears to have
      changed little since the 1950s. Textbooks are organized according to organ
      systems and describe methods of eliciting and recording history and PE data using
      a routine format. In many medical schools, the preclinical teaching programs for
      clinical examination skills similarly emphasize an orderly collection of data.
      Teaching students to use diagnostic reasoning is postponed until students have
      learned history-taking and PE skills. The authors propose three modifications to
      this educational approach. First, rather than performing the clinical examination
      using a routine format, students should be encouraged to form diagnostic
      hypotheses early on while listening to the patient's narrative, and conduct the
      subsequent search for history and PE data in a reflective way in order to confirm
      or refute these hypotheses. Second, the authors propose that interviewing
      patients and conducting the PE be taught by one-on-one tutoring until students
      achieve mastery. Last, they suggest that the PE be guided not only by students'
      diagnostic hypotheses, but also by patients' expectations. These modifications
      are consistent with current trends in medical education that encourage a
      reflective practice and problem-based learning (PBL), and they also introduce
      medical students to the precepts of clinical reasoning. The authors suggest that
      challenging students to seek specific physical findings may increase the
      likelihood of detecting findings when they are present, and may transform patient
      interviewing and conducting the PE from routine activities into intellectually
      exciting experiences.

PMID- 16306286
TI  - Specifying student-patient encounters, web-based case logs, and meeting standards
      of the liaison committee on medical education.
AB  - Standard ED-2 of the Liaison Committee on Medical Education (LCME) requires
      medical schools to specify the types of patients that students should encounter,
      the student's level of responsibility, and the appropriate setting for the
      encounter. The authors describe the process at Joan and Sanford I. Weill Medical
      College of Cornell University in New York City for meeting this standard through
      the development of a Web-based case log. The log permits the medical college to
      specify expectations for patient encounters and allows the students to record
      their encounters in an efficient, brief, and user-friendly manner. By downloading
      the student's reports directly into a database, the medical college can track
      successes and deficiencies in the student's clinical experiences. However, in
      response to a questionnaire administered in 2005, students generally expressed
      dissatisfaction with the case logs, which they described as intrusive busywork.

PMID- 16306287
TI  - Contextual considerations in summative competency examinations: relevance to the
      long case.
AB  - Long-case patient-based examinations previously formed the basis of summative
      competency testing in physician certification examinations. These exams were
      found to be unreliable and have fallen from favor. During the authors'
      deliberation of the long case in the neurology certification examinations of the
      Royal College of Physicians and Surgeons of Canada, they considered the
      examination context and concluded that the appropriate psychometric analysis of
      the exams is highly contingent on the context. The examination context underlying
      certification examinations has evolved considerably; within a different context,
      a more cohesive test system based on a quality assurance framework could better
      manage substantive psychometric issues around case specificity,
      comprehensiveness, reliability, and compensability. These arguments are in small
      part psychometric, but are mostly philosophical and have relevance to the
      profession and the public.

PMID- 16306290
TI  - A medical experience that taught me about humanism in medicine: burn in.

PMID- 16306291
TI  - A medical experience that taught me about humanism in medicine: Rolando.

PMID- 16306292
TI  - Medical ethics education: where are we? Where should we be going? A review.
AB  - PURPOSE: The authors' primary goal was to provide a comprehensive and current
      review of the literature surrounding ethics education for medical students.
      Following this review, the authors summarize the deficits in the current
      literature and provide recommendations for future inquiries on medical ethics
      education. METHOD: In 2004, the authors searched MEDLINE and PubMed using the
      following search terms: ethics, ethics education, medical ethics education,
      curriculum, undergraduate medical education, virtue, role model, philosophy of
      medicine, and outcomes research. No limit was placed on dates for this literature
      search. Articles whose primary focus was professionalism were excluded because
      the professionalism literature tends to focus on competencies and postgraduate
      education, whereas the primary focus of this study was on undergraduate
      education. Literature on physicians as role models to medical students as a form
      of teaching medical ethical ethics was excluded as well because the current
      discussion examines the formal undergraduate medical ethics curricula. Also
      excluded were reports from foreign countries (unless there were no equivalent
      studies in the United States). The authors found almost no literature exploring
      students' backgrounds (cultural, religious, socioeconomic, etc.) and the teaching
      of medical ethics in medical schools. Otherwise, the authors reviewed everything
      they could find, regardless of imperfections in individual reports such as small
      sample size or poor research methodology. RESULTS: The review, which encompassed
      articles from 1978 to 2004, revealed that deep shortcomings exist in the
      literature on medical ethics education. Deficits exist in all areas of the
      literature: (1) theoretical work done on the overall goals of medical ethics
      education; (2) empirical studies that attempt to examine outcomes for students;
      (3) studies examining teaching methods in medical ethics education, and (4)
      studies evaluating the effectiveness of various teaching methods. CONCLUSIONS:
      There are substantial opportunities for contribution to the literature on medical
      ethics education in all of the areas where deficits exist. The literature
      suggests that two points of view exist regarding the purpose of teaching medical
      ethics: (1) that it is a means of creating virtuous physicians; and (2) that it
      is a means of providing physicians with a skill set for analyzing and resolving
      ethical dilemmas. This dichotomy made it difficult to arrive at a consensus
      regarding the goals of medical ethics education. The field would benefit from
      further theoretical work aimed at better delineating the core content, core
      processes, and core skills relevant to the ethical practice of medicine. The time
      has come to organize an effort to improve and validate medical ethics education.
      In the end, effective medical ethics education will further the goals of medicine
      in dramatic and tangible ways.

PMID- 16306293
TI  - The influence of teaching setting on medical students' clinical skills
      development: is the academic medical center the "gold standard"?
AB  - PURPOSE: Many medical schools have revised their curricula to include
      longitudinal clinical training in the first and second years, placing an extra
      burden on academic teaching faculty and expanding the use of community-based
      preceptors for clinical teaching. Little is known about the impact of different
      learning settings on clinical skills development. METHOD: In 2002-03 and 2003-04,
      the authors evaluated the clinical skills of two sequential cohorts of second
      year medical students at Dartmouth Medical School (n = 155) at the end of a two
      year longitudinal clinical course designed to prepare them for their clerkship
      year. Students' objective structured clinical examination (OSCE) scores were
      compared on a cardiopulmonary and an endocrine case according to precepting sites
      (academic medical center [AMC] clinics, AMC-affiliated office-based clinics, or
      community-based primary care offices) and core communication, history taking,
      physical examination, and patient education skills were assessed. Study groups
      were compared using descriptive statistics and analysis of variance (mixed
      model). RESULTS: Ninety-five students (61%) had community-based preceptors, 31
      (20%) AMC clinic-based preceptors, and 29 (19%) AMC-affiliated office-based
      preceptors. Students' performances did not differ among clinical learning sites
      with overall scores in the cardiopulmonary case of 61.2% in AMC clinics, 63.3% in
      office-based AMC-affiliated clinics, and 64.9% in community-based offices (p =
      .20). Scores in the endocrine case similarly did not differ with overall scores
      of 65.5% in AMC clinics, 68.5% in office-based AMC-affiliated clinics, and 66.4%
      in community-based offices (p = .59). CONCLUSIONS: Students' early clinical skill
      development is not influenced by educational setting. Thus, using clinicians for
      early clinical training in any of these settings is appropriate.

PMID- 16306294
TI  - Female patients' preferences related to interpersonal communications, clinical
      competence, and gender when selecting a physician.
AB  - PURPOSE: In obstetrics and gynecology (ob-gyn), a physician's gender can affect
      patients' access to care as well as medical education curricula and career
      counseling. The authors focused on the importance that female patients place on
      various physician characteristics, and how this importance varied by patients'
      characteristics and compared for family practitioners, obstetrician
      gynecologists, and surgeons. METHOD: In 1999-2000, an anonymous questionnaire was
      distributed for one week to all women scheduled for an ob-gyn visit at six
      community campuses of Michigan State University College of Human Medicine. The
      first section of the questionnaire listed 16 physician characteristics and asked
      patients to rate the importance of each using a six-point scale (1 = not at all
      important, to 6 = very important). The items were presented three times, in
      reference to the patients' choice of a family physician, ob-gyn, and surgeon. The
      questionnaire also asked for patients' demographic information. Descriptive
      statistics were used to summarize patient demographics and ratings. Multivariate
      relationships were tested using analyses of variance (repeated-measures analysis
      of variance [ANOVA]) and multiple regression. RESULTS: In the 1,059 completed
      questionnaires, items related to physician gender were among the lowest rated,
      regardless of specialty. A factor analysis resulted in a three factor solution:
      Interpersonal Communications, Clinical Competence, and Gender. Interpersonal
      Communications ratings varied least by physician specialty and patient
      characteristics; Gender ratings varied most. Physician behaviors rather than
      physician attributes play an important role in women's choices. CONCLUSIONS: For
      most women, physician gender was one of the least important characteristics,
      regardless of specialty. Excellent skills might give all physicians an edge in
      patients' choice decisions, a finding contrary to widely held beliefs about more
      limited future opportunities for men in some specialties.

PMID- 16306295
TI  - Improving safety and reducing harm associated with specialized nutrition support.

PMID- 16306296
TI  - Twenty-five years of advances in vascular access: bridging research to clinical
      practice.
AB  - Vascular access has become a key component for a multitude of IV therapies,
      including parenteral nutrition. Access of the central venous system has been long
      recognized for its associated complications of infection, thrombosis, and
      occlusion. Over the past 25 years, clinical practice based on research and
      innovation has attempted to decrease complication rates and therefore improve the
      safety of vascular access. This article highlights the research and its influence
      on catheter care procedures, technology, and education that has led to advances
      in vascular access. An improved understanding of the pathophysiology associated
      with catheter-related complications and an ongoing evaluation of new treatment
      modalities has provided clinicians today with new options for improved patient
      care and the ability to preserve vascular access options for patients.

PMID- 16306297
TI  - Gastrostomy tube placement outcomes: comparison of surgical, endoscopic, and
      laparoscopic methods.
AB  - BACKGROUND: Advances in percutaneous endoscopic gastrostomy (PEG) and
      laparoscopic (LAP) techniques now allow for less invasive placement of
      gastrostomy tubes. This study compared morbidities and feeding outcomes of these
      procedures with standard surgical (OPEN) insertion. METHODS: Gastrostomy tubes
      placed in the operating room by the PEG, LAP, and OPEN methods were compared for
      insertion times, tube insertion and maintenance complications, enteral feeding
      complications, and feeding start days. Patients with concomitant intra-abdominal
      procedures were excluded. Patients were followed for 6 days after tube placement.
      RESULTS: A total of 91 catheters (PEG = 23, LAP = 39, OPEN = 29) were inserted in
      the operating room for indications of ventilator-dependent respiratory failure
      (45), dysphagia (30), head and neck cancer (9), and decreased mental status (7).
      No patients were fed on the day of the procedure. Insertion times were
      significantly longer (p < .05) in the OPEN technique (68 minutes) vs LAP (48
      minutes) and PEG (30 minutes). Insertion complications occurred in the LAP and
      PEG cohorts (3 failed LAP, 1 failed PEG), and maintenance complications were
      higher in the LAP group, including 1 episode each of cellulitis, bleeding, and
      serous drainage. Twenty enteral feeding complications in 17 patients occurred in
      all groups (9 in LAP vs 6 in PEG and 5 in OPEN), and included emesis (6), high
      residual (5), diarrhea (3), ileus (3), nausea (2), and pain after feeding (1).
      Overall complications were significantly lower in the PEG (7) and OPEN (5) groups
      compared with the LAP group (15). Feeding start day was significantly delayed in
      the OPEN technique (2.1 days vs 1.7 in PEG and 1.5 in LAP); however, no
      difference was found in days to goal among groups (4.4-4.8 days). CONCLUSIONS:
      PEG should be the procedure of choice for placement of gastrostomy tubes. If PEG
      is contraindicated, then OPEN technique may be best due to fewer complications,
      although insertion time is longer than the LAP technique.

PMID- 16306298
TI  - Percutaneous endoscopic gastrostomy evaluation of device materials: are we
      "failsafe"?
AB  - The development of the percutaneous endoscopic gastrostomy (PEG) tube for enteral
      access was a revolutionary technological advance. This device has undergone some
      minor modification over the past 30 years but remains very similar to the
      original PEG tube design. Use of the PEG tube for gastric enteral feeding access
      continues to increase yearly both in pediatric and adult populations. One of the
      difficulties noted with PEG tube use in daily clinical practice is the ultimate
      degradation of the PEG tube wall material, leading to tube cracking, tearing, and
      leaking, requiring replacement of the gastrostomy tube. Historically, the
      predominant polymer material used for PEG tube composition was silicone. More
      recently, polyurethane has been examined as a potential, more durable material
      for PEG tube composition. Copolymers, or combinations of silicone and
      polyurethane and other polymer materials, are currently under investigation as
      the answer for the development of a bioinert, tissue-friendly, durable, PEG tube
      composition material.

PMID- 16306299
TI  - Enteral nutrition and drug administration, interactions, and complications.
AB  - The enteral route has become the standard of care to deliver nutrition support
      for hospitalized acute care and ambulatory care patients. The same access device
      is increasingly being used to deliver medications, which provides cost savings
      but also creates new challenges. Cost savings can be negated if the concomitant
      administration of nutrition elicits a decrease in bioavailability due to
      incompatibilities that alter drug or nutrition therapy. Feeding tubes can deliver
      nutrients and drugs to the stomach, small bowel, or both, with optimal efficacy
      of medications depending on delivery to the appropriate segment of the
      gastrointestinal tract. Liquid preparations are often the preferred formulation
      for enteral administration. Obstruction of the enteral access device may occur
      when specialized medication formulations are altered inappropriately.
      Occasionally, the enteral formula should be changed to modify the content of free
      water, fiber, electrolytes, or vitamins that may interfere with the drug therapy.
      Intolerance to enteral nutrition such as abdominal distention and diarrhea may be
      the result of the medication, and the causative agent should be identified to
      improve patient comfort. This article will address optimal drug delivery via
      enteral access devices and possible complications associated with therapy.

PMID- 16306300
TI  - Review of the refeeding syndrome.
AB  - Refeeding syndrome describes a constellation of metabolic disturbances that occur
      as a result of reinstitution of nutrition to patients who are starved or severely
      malnourished. Patients can develop fluid and electrolyte disorders, especially
      hypophosphatemia, along with neurologic, pulmonary, cardiac, neuromuscular, and
      hematologic complications. We reviewed literature on refeeding syndrome and the
      associated electrolyte abnormalities, fluid disturbances, and associated
      complications. In addition to assessing scientific literature, we also considered
      clinical experience and judgment in developing recommendations for prevention and
      treatment of refeeding syndrome. The most important steps are to identify
      patients at risk for developing refeeding syndrome, institute nutrition support
      cautiously, and correct and supplement electrolyte and vitamin deficiencies to
      avoid refeeding syndrome. We provide suggestions for the prevention of refeeding
      syndrome and suggestions for treatment of electrolyte disturbances and
      complications in patients who develop refeeding syndrome, according to evidence
      in the literature, the pathophysiology of refeeding syndrome, and clinical
      experience and judgment.

PMID- 16306301
TI  - D-lactic acidosis.
AB  - D-lactic acidosis, also referred to as D-lactate encephalopathy, is a rare
      neurologic syndrome that occurs in individuals with short bowel syndrome or
      following jejuno-ileal bypass surgery. Symptoms typically present after the
      ingestion of high-carbohydrate feedings. Neurologic symptoms include altered
      mental status, slurred speech, and ataxia, with patients often appearing drunk.
      Onset of neurologic symptoms is accompanied by metabolic acidosis and elevation
      of plasma D-lactate concentration. In these patients, malabsorbed carbohydrate is
      fermented by an abnormal bacterial flora in the colon, which produces excessive
      amounts of D-lactate. High amounts of D-lactate are absorbed into the
      circulation, resulting in an elevated concentration of D-lactate in the blood.
      Development of neurologic symptoms has been attributed to D-lactate, but it is
      unclear if this is the cause or whether other factors are responsible. This
      review examines the pathophysiology of the production and accumulation of D
      lactate while exploring the potential factors contributing to the development of
      neurologic manifestations. Methods of diagnosis and treatment are reviewed. Areas
      requiring further investigation are identified.

PMID- 16306302
TI  - Long-term enteral nutrition support and the risk of dehydration.
AB  - Dehydration is a serious risk for the long-term tube-fed patient who is not
      allowed oral intake, has an altered mental status, is unable to communicate, is
      elderly or fluid-restricted, or has thirst impairment. The intent of this review
      is to provide a case-based discussion regarding the evaluation, treatment, and
      prevention of dehydration in these types of patients. Identification of risk
      factors, along with evaluation of subjective, objective, and laboratory
      parameters, provides the basis for clinical evaluation. "Hidden" sources of fluid
      intake such as the water content of solid foods and water generated from nutrient
      oxidation and "hidden" sources of fluid output such as evaporative losses should
      be considered in waterbalance calculations. The method for treatment and
      prevention of dehydration depends on the presence or absence of hypovolemia, type
      of body fluid losses, and whether the patient demonstrates hypernatremia,
      normonatremia, or hyponatremia.

PMID- 16306303
TI  - Understanding clinical issues in postoperative nutrition after
      pancreaticoduodenectomy.
AB  - Postoperative nutrition support for patients undergoing pancreaticoduodenectomy
      (Whipple's procedure) may be complicated due to gastrointestinal tract
      dysfunction (gastroparesis, dumping, and malabsorption) subsequent to the
      procedure. Clinical management of these patients may be adversely affected by
      procedure-specific knowledge deficits (method of gastrointestinal [GI]
      reconstruction), common and expected surgical complications, and the available
      route for alimentation. It is the aim of this report to provide the reader with
      an overview of the procedure, common postoperative nutrition issues, and
      available interventions.

PMID- 16306304
TI  - Oxidative stress and antioxidant capacity in smoking and nonsmoking men with
      HIV/acquired immunodeficiency syndrome.
AB  - BACKGROUND: Past studies document decreased levels of antioxidants and selenium
      and increased levels of oxidative stress in people living with HIV/acquired
      immunodeficiency syndrome (AIDS). Cigarette smoking is another source of
      oxidative stress. Excessive oxidative stress can induce HIV replication,
      resulting in disease progression. The purpose of this study was to determine
      whether subjects with HIV/AIDS who smoke cigarettes have increased oxidative
      stress and decreased antioxidant status compared with nonsmokers with HIV/AIDS.
      METHODS: Thirty-one men with HIV/AIDS (adhering to highly active antiretroviral
      therapy for the previous 3 months) were recruited during regular visits to a
      Veterans Affairs Medical Center Infectious Disease Clinic in a southeastern US
      city. Plasma was obtained from a 1-time blood draw for this comparison study.
      Plasma lipid peroxide (LPO) was used as a marker of oxidative stress. Indicators
      of antioxidant capacity included plasma glutathione peroxidase (GPx, the
      functional indicator of selenium status), vitamin C, and antioxidant potential
      (AOP). RESULTS: Fifteen smokers and 10 nonsmokers with HIV/AIDS were enrolled.
      Median plasma LPO level was above the normal range of 0-1.3 micromol/L in both
      nonsmokers (2.5 [0-23.4] micromol/L, median [range]) and smokers (4.0 [0-47.5]
      micromol/L), but there was no difference between groups. Plasma GPx concentration
      was significantly lower in smokers (169 [118-295] mumol/min/L) compared with
      nonsmokers (197 [149-414] micromol/min/L). Vitamin C and AOP levels were not
      different between groups. CONCLUSIONS: This pilot study suggests that effects of
      smoking on oxidative stress are not additive, as no striking differences were
      observed in oxidative stress or antioxidant capacity between clinically stable
      smoking and nonsmoking men with HIV/AIDS.

PMID- 16306305
TI  - Alterations in lipid profiles in HIV-infected patients treated with protease
      inhibitor therapy are not influenced by diet.
AB  - BACKGROUND: The use of protease inhibitor (PI) -based highly active
      antiretroviral therapy (HAART) in patients infected with human immunodeficiency
      virus (HIV) has been linked to alterations in lipid profiles. METHODS:
      Longitudinal cohort study. Lipid profiles were evaluated pre- and post-PI therapy
      in 49 HIV-infected patients. Diet was also evaluated to determine any
      contribution to alterations in lipid levels. RESULTS: Pre- and post-PI-based
      HAART samples were examined from 42 men and 7 women, mean age 40.6 years. Mean
      CD4 count pre-PI was 242 +/- 205 cells/mm(3); HIV RNA was 4.2 log(10) copies/mL;
      body mass index (BMI) was 24.7 +/- 3.6 kg/m(2); body fat was 17.1 +/- 9.1 kg by
      bioelectrical impedance analysis (BIA), dietary intake was 2654 +/- 732 kcal/day.
      Post-PI samples were collected 5.7 +/- 1.66 months after starting therapy. CD4
      counts increased to 384 +/- 323 cells/mm(3) and RNA decreased 1 log post-PI. Post
      PI BMI (25.2 kg/m2), percent body fat (17.4%) and caloric intake (2656 kcal/day)
      were unchanged. Pre-PI total cholesterol (TC) in men was 167.6 +/- 42.4 mg/dL; TC
      increased (190.4 +/- 47.9 mg/dL) post-PI (p < .0001). Pre-PI triglycerides (TG)
      were 154.5 +/- 109.4 mg/dL; TG increased post-PI (266.1 +/- 363.6 mg/dL, p <
      .03). Low-density lipoprotein (LDL) -C was 97.8 +/- 31 mg/dL pre-PI and rose to
      107.1 +/- 34.7 mg/dL post-PI (p < .05). High density lipoproteins (HDLs) were
      below desired levels before initiation of PI therapy and remained low.
      CONCLUSIONS: PI therapy significantly alters lipid profiles in HIV-infected
      patients. Dietary intake did not contribute to changes in lipid profile. More
      longitudinal studies are needed to demonstrate whether these alterations
      contribute to additional cardiovascular risk.

PMID- 16306306
TI  - Adding dietary green beans resolves the diarrhea associated with bowel surgery in
      neonates: a case study.
AB  - Feeding intolerance is a common problem in infants who have had multiple or
      extensive resections of their small bowel. Chronic malabsorption and diarrhea are
      common side effects that inhibit the advancement of enteral feedings and prolong
      dependence on parenteral nutrition (PN). Poor growth, recurrent central line
      infections, cholestasis, and osteopenia are well-known complications associated
      with long-term PN dependency. It has been shown that, in adults with short bowel
      syndrome, providing dietary fiber can improve tolerance to enteral feeding. There
      are no published studies that have addressed the influence of dietary fiber on
      feeding intolerance in infants after bowel resections. The ensuing case studies
      illustrate the positive outcomes of fiber use in infants with diarrhea secondary
      to small bowel resections.

PMID- 16306307
TI  - Geographic prediction of human onset of West Nile virus using dead crow clusters:
      an evaluation of year 2002 data in New York State.
AB  - The risk of becoming a West Nile virus case in New York State, excluding New York
      City, was evaluated for persons whose town of residence was proximal to spatial
      clusters of dead American crows (Corvus brachyrhynchos). Weekly clusters were
      delineated for June-October 2002 by using both the binomial spatial scan
      statistic and kernel density smoothing. The relative risk of a human case was
      estimated for different spatial-temporal exposure definitions after adjusting for
      population density and age distribution using Poisson regression, adjusting for
      week and geographic region, and conducting Cox proportional hazards modeling,
      where the week that a human case was identified was treated as the failure time
      and baseline hazard was stratified by region. The risk of becoming a West Nile
      virus case was positively associated with living in towns proximal to dead crow
      clusters. The highest risk was consistently for towns associated with a cluster
      in the current or prior 1-2 weeks. Weaker, but positive associations were found
      for towns associated with a cluster in just the 1-2 prior weeks, indicating an
      ability to predict onset in a timely fashion.

PMID- 16306308
TI  - Epidemiology of musculoskeletal injuries among high school cross-country runners.
AB  - To determine the incidence of lower-extremity injury among high school cross
      country runners and to identify risk factors for injury, the authors
      prospectively monitored a cohort of 421 runners competing on 23 cross-country
      teams in 12 Seattle, Washington, high schools during the 1996 cross-country
      season. Collected were daily injury and athletic exposure (AE) reports, a
      baseline questionnaire on prior running and injury experience, anthropometric
      measurements, and coaches' training logs. The overall incidence rate of injury
      was 17.0/1,000 AEs. Girls had a significantly higher overall injury rate
      (19.6/1,000 AEs) than boys did (15.0/1,000 AEs) (incidence rate ratio = 1.3, 95%
      confidence interval: 1.0, 1.6). Compared with boys, girls had significantly
      higher rates of injuries resulting in >or=15 days of disability. For the overall
      sample and for girls, Cox regression revealed that a quadriceps angle of >or=20
      degrees and an injury during summer running prior to the season were the most
      important predictors of injury. For boys, a quadriceps angle of >or=15 degrees
      and a history of multiple running injuries were most associated with injury.
      Results suggest that the incidence of lower-extremity injuries is high for cross
      country runners, especially girls. Preseason screening to determine risk factors
      should be examined as a preventive approach for identifying high-risk runners.

PMID- 16306309
TI  - Iron deficiency and Helicobacter pylori infection in the United States.
AB  - Using data from the current National Health and Nutrition Examination Survey
      (1999-2000), the authors assessed whether Helicobacter pylori infection is
      associated with iron deficiency and iron-deficiency anemia (IDA) in the United
      States. Iron deficiency was defined as at least two abnormal results out of three
      biomarkers of iron stores. IDA was defined as a low hemoglobin level in the
      presence of iron deficiency. H. pylori infection was measured by serology.
      Complex survey estimators were used in the analysis. For 7,462 survey
      participants aged >or=3 years, H. pylori infection was associated with decreased
      serum ferritin levels (percent change = -13.9%, 95% confidence interval (CI): 
      19.5, -8.0) but not with levels of free erythrocyte protoporphyrin, transferrin
      saturation, or hemoglobin (percent change = 1.5%, -2.8%, and -1.1%,
      respectively). Multinomial logistic regression analyses indicated that H. pylori
      infection was associated with the prevalence of IDA (prevalence odds ratio (POR)
      = 2.6, 95% CI: 1.5, 4.6) and, to a lesser degree, other types of anemia (POR =
      1.3, 95% CI: 1.0, 1.7). H. pylori infection was associated with a 40% increase in
      the prevalence of iron deficiency (POR = 1.4, 95% CI: 0.9, 2.0) after controlling
      for relevant covariates. In the United States, H. pylori infection was associated
      with iron deficiency/IDA regardless of the presence or absence of peptic ulcer
      disease.

PMID- 16306310
TI  - Comparison between two quasi-induced exposure methods for studying risk factors
      for road crashes.
AB  - This study was designed to compare estimates from two quasi-induced exposure
      methods of the effects of driver- and vehicle-related conditions on the risk of
      causing a road crash for drivers of vehicles with four or more wheels. From the
      Spanish register of road crashes with victims, the authors selected, for 1993
      2002, all 755,329 drivers of >or=4-wheeled vehicles involved in single-vehicle
      crashes or in two-vehicle collisions in which only one of the drivers was
      considered responsible. Multinomial and logistic regression models were used to
      obtain the odds ratio for each driver- and vehicle-related variable. Construction
      of these models was based on the assumptions of classical quasi-induced exposure
      methods and on the method (a paired-by-collision analysis of responsible and
      nonresponsible drivers) proposed by Perneger and Smith (Am J Epidemiol
      1991;134:1138-45). The main driver-dependent conditions for any type of crash
      were psychophysical circumstances (alcohol use and sleepiness). The effect of
      most driver- and vehicle-related characteristics was higher for single-vehicle
      crashes than for two-vehicle collisions. Furthermore, both classical and paired
      by-collision analyses yielded similar estimates and can be considered equally
      useful alternatives for assessing the effect of driver and vehicle
      characteristics on the risk of causing a collision between two vehicles.

PMID- 16306311
TI  - Serum antioxidants, inflammation, and total mortality in older women.
AB  - The inflammatory cytokine interleukin-6 (IL-6) has been linked to poor health
      outcomes in older adults. Oxidative stress triggers the production of IL-6, and
      antioxidant micronutrients play a critical role in decreasing this inflammatory
      response. The authors sought to identify the relations between serum levels of
      antioxidant nutrients and IL-6 and mortality in older women. Levels of alpha- and
      beta-carotene, lycopene, lutein/zeaxanthin, alpha-cryptoxanthin, total
      carotenoids, retinol, alpha-tocopherol, zinc, and selenium were measured at
      baseline in 619 participants in Women's Health and Aging Study I (Baltimore,
      Maryland, 1992-1998). IL-6 was measured at baseline and at follow-up 1 and 2
      years later, and all-cause mortality was determined over a 5-year period.
      Participants with the highest serum levels of alpha-carotene, total carotenoids,
      and selenium were significantly less likely to be in the highest tertile of serum
      IL-6 at baseline (p < 0.0001). Those with the lowest levels of alpha- and beta
      carotene, lutein/zeaxanthin, and total carotenoids were significantly more likely
      to have increasing IL-6 levels over a period of 2 years. Those with the lowest
      selenium levels had a significantly higher risk of total mortality over a period
      of 5 years (hazard ratio = 1.54, 95% confidence interval: 1.03, 2.32). These
      findings suggest that specific antioxidant nutrients may play an important role
      in suppressing IL-6 levels in disabled older women.

PMID- 16306312
TI  - Antioxidant intake and risk of osteoporotic hip fracture in Utah: an effect
      modified by smoking status.
AB  - The role of antioxidant intake in osteoporotic hip fracture risk is uncertain and
      may be modified by smoking. In the Utah Study of Nutrition and Bone Health, a
      statewide, population-based case-control study, the authors investigated whether
      antioxidant intake was associated with risk of osteoporotic hip fracture and
      whether this association was modified by smoking status. The analyses included
      data on 1,215 male and female cases aged > or = 50 years who incurred a hip
      fracture during 1997-2001 and 1,349 age- and sex-matched controls. Diet was
      assessed by food frequency questionnaire. Among ever smokers, participants in the
      highest quintile of vitamin E intake (vs. the lowest) had a lower risk of hip
      fracture after adjustment for confounders (odds ratio = 0.29, 95% confidence
      interval (CI): 0.16, 0.52; p-trend < 0.0001). The corresponding odds ratio for
      beta-carotene intake was 0.39 (95% CI: 0.23, 0.68; p-trend = 0.0004), and for
      selenium intake it was 0.27 (95% CI: 0.12, 0.58; p-trend = 0.0003). Vitamin C
      intake did not have a significant graded association with hip fracture risk among
      ever smokers. Similar findings were obtained when an overall antioxidant intake
      score was used (odds ratio = 0.19, 95% CI: 0.10, 0.37; p-trend < 0.0001). No
      similar associations were found in never smokers. Antioxidant intake was
      associated with reduced risk of osteoporotic hip fracture in these elderly
      subjects, and the effect was strongly modified by smoking status.

PMID- 16306313
TI  - Statistical issues in life course epidemiology.
AB  - There is growing recognition that the risk of many diseases in later life, such
      as type 2 diabetes or breast cancer, is affected by adult as well as early-life
      variables, including those operating prior to conception and during the prenatal
      period. Most of these risk factors are correlated because of common biologic
      and/or social pathways, while some are intrinsically ordered over time. The study
      of how they jointly influence later ("distal") disease outcomes is referred to as
      life course epidemiology. This area of research raises several issues relevant to
      the current debate on causal inference in epidemiology. The authors give a brief
      overview of the main analytical and practical problems and consider a range of
      modeling approaches, their differences determined by the degree with which
      associations present (or presumed) among the correlated explanatory variables are
      explicitly acknowledged. Standard multiple regression (i.e., conditional) models
      are compared with joint models where more than one outcome is specified. Issues
      arising from measurement error and missing data are addressed. Examples from two
      cohorts in the United Kingdom are used to illustrate alternative modeling
      strategies. The authors conclude that more than one analytical approach should be
      adopted to gain more insight into the underlying mechanisms.

PMID- 16306314
TI  - Exposure-effect relations between aircraft and road traffic noise exposure at
      school and reading comprehension: the RANCH project.
AB  - Transport noise is an increasingly prominent feature of the urban environment,
      making noise pollution an important environmental public health issue. This paper
      reports on the 2001-2003 RANCH project, the first cross-national epidemiologic
      study known to examine exposure-effect relations between aircraft and road
      traffic noise exposure and reading comprehension. Participants were 2,010
      children aged 9-10 years from 89 schools around Amsterdam Schiphol, Madrid
      Barajas, and London Heathrow airports. Data from The Netherlands, Spain, and the
      United Kingdom were pooled and analyzed using multilevel modeling. Aircraft noise
      exposure at school was linearly associated with impaired reading comprehension;
      the association was maintained after adjustment for socioeconomic variables (beta
      = -0.008, p = 0.012), aircraft noise annoyance, and other cognitive abilities
      (episodic memory, working memory, and sustained attention). Aircraft noise
      exposure at home was highly correlated with aircraft noise exposure at school and
      demonstrated a similar linear association with impaired reading comprehension.
      Road traffic noise exposure at school was not associated with reading
      comprehension in either the absence or the presence of aircraft noise (beta =
      0.003, p = 0.509; beta = 0.002, p = 0.540, respectively). Findings were
      consistent across the three countries, which varied with respect to a range of
      socioeconomic and environmental variables, thus offering robust evidence of a
      direct exposure-effect relation between aircraft noise and reading comprehension.

PMID- 16306315
TI  - Specific projection of the sensory crypt cells in the olfactory system in crucian
      carp, Carassius carassius.
AB  - To study the projection of a special type of sensory neuron called crypt cells in
      the olfactory system in crucian carp, Carassius carassius, we applied the neural
      tracer 1,1-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) in
      the olfactory bulb (OB). Small crystals of DiI were applied in a small area at
      the synaptic region at the ventral part of the OB, where a population of
      secondary neurons specific for sex pheromones has been identified. In those
      samples (4 out of 24) where only axons in the lateral bundle of the medial
      olfactory tract were stained, the majority (50-66%) of olfactory sensory neurons
      stained were crypt cells situated in the peripheral layer of the olfactory
      epithelium. Because this bundle of the tract mediates reproductive behavior, it
      is conceivable that crypt cells express olfactory receptors for sex pheromones.

PMID- 16306317
TI  - Taste, salience, and increased NaCl ingestion after repeated sodium depletions.
AB  - Previous studies have shown that repeated sodium depletions using the natriuretic
      diuretic furosemide induce progressive increases in NaCl ingestion. We
      investigated the role of taste in this behavioral sensitization in Sprague-Dawley
      rats using short-term lickometer testing along with 2-h stimulated intake tests.
      Our results show maximal licking across a range of NaCl concentrations after each
      of the three depletions, regardless of whether the solutions contained sucrose or
      were presented alone. Similarly, the presence of sucrose did not affect
      stimulated NaCl intake in long-term tests, although ingestion of NaCl solutions
      increased progressively with successive depletions. Finally, both licking and
      ingestion returned to baseline levels during need-free conditions. These results
      suggest that sodium imbalance acutely increases the salience of sodium taste and
      thereby the likelihood of NaCl ingestion, which may, in turn, contribute to
      progressive increases in NaCl intake that occur with multiple furosemide-induced
      sodium depletions.

PMID- 16306316
TI  - A Drosophila nonvisual arrestin is required for the maintenance of olfactory
      sensitivity.
AB  - Nonvisual arrestins are a family of multifunctional adaptor molecules that
      regulate the activities of diverse families of receptors including G protein
      coupled receptors, frizzled, and transforming growth factor-beta receptors. These
      activities indicate broad roles in both physiology and development for nonvisual
      arrestins. Drosophila melanogaster has a single nonvisual arrestin, kurtz, which
      is found at high levels within the adult olfactory receptor neurons (ORNs),
      suggesting a role for this gene in modulating olfactory sensitivity. Using heat
      induced expression of a krz cDNA through development, we rescued krz(1)
      lethality. The resulting adults lacked detectable levels of krz in the olfactory
      system. The rescued krz(1) homozygotes have an incompletely penetrant antennal
      structural defect that was completely rescued by the neural expression of a krz
      cDNA. The krz(1) loss-of-function adults without visible antennal defects
      displayed diminished behavioral responsiveness to both aversive and attractive
      odors and also demonstrated reduced olfactory receptor potentials. Both the
      behavioral and electrophysiological phenotypes were rescued by the targeted
      expression of the krz cDNA within postdevelopmental ORNs. Thus, krz is required
      within the nervous system for antennal development and is required later in the
      ORNs for the maintenance of olfactory sensitivity in Drosophila. The reduced
      receptor potentials in krz(1) antenna indicate that nonvisual arrestins are
      required for the early odor-induced signaling events within the ORNs.

PMID- 16306318
TI  - Mechanical obstruction of the olfactory cleft reveals differences between
      orthonasal and retronasal olfactory functions.
AB  - Following up on recent observations in patients with nasal polyposis (NP), the
      present study aimed to investigate whether a mechanical obstruction of the
      anterior olfactory cleft (OC) would produce differential effects on orthonasal
      and retronasal olfactory functions. To this end, we studied 33 healthy subjects
      in a randomized trial. Sponges with high content of saline were either placed in
      the OC or on the respiratory epithelium, such that this was blinded to both
      subject and observer. The results indicated that orthonasal (P = 0.04) but not
      retronasal (P = 0.15) olfactory identification ability was lower when the OC was
      blocked. This confirms the idea that differences between orthonasal and
      retronasal olfactory functions, as observed in NP patients, are, at least to some
      degree, due to mechanical obstruction of the anterior portion of the OC. The
      present data also suggest that mechanical obstruction is a means to induce
      reversible hyposmia void of side effects which can be performed in a blinded
      fashion. This might become a valuable model of hyposmia for future
      investigations.

PMID- 16306319
TI  - Evaluation of the validity of a maximum likelihood adaptive staircase procedure
      for measurement of olfactory detection threshold in mice.
AB  - Threshold is defined as the stimulus intensity necessary for a subject to reach a
      specified percent correct on a detection test. MLPEST (maximum likelihood
      parameter estimation by sequential testing) is a method that is able to determine
      threshold accurately and more rapidly than many other methods. Originally
      developed for human auditory and visual tasks, it has been adapted for human
      olfactory and gustatory tests. In order to utilize this technique for olfactory
      testing in mice, we have adapted MLPEST methodology for use with computerized
      olfactometry as a tool to estimate odor detection thresholds. Here we present
      Monte Carlo simulations and operant conditioning data that demonstrate the
      potential utility of this technique in mice, we explore the ramifications of
      altering MLPEST test parameters on performance, and we discuss the advantages and
      disadvantages of using MLPEST compared to other methods for the estimation of
      thresholds in rodents. Using MLPEST, we find that olfactory detection thresholds
      in mice deficient for the cyclic nucleotide-gated channel subunit A2 are similar
      to those of wild-type animals for odorants the knockout animals are able to
      detect.

PMID- 16306320
TI  - Connection patterns distinguish 3 regions of human parietal cortex.
AB  - Three regions of the macaque inferior parietal lobule and adjacent lateral
      intraparietal sulcus (IPS) are distinguished by the relative strengths of their
      connections with the superior colliculus, parahippocampal gyrus, and ventral
      premotor cortex. It was hypothesized that connectivity information could
      therefore be used to identify similar areas in the human parietal cortex using
      diffusion-weighted imaging and probabilistic tractography. Unusually, the
      subcortical routes of the 3 projections have been reported in the macaque, so it
      was possible to compare not only the terminations of connections but also their
      course. The medial IPS had the highest probability of connection with the
      superior colliculus. The projection pathway resembled that connecting parietal
      cortex and superior colliculus in the macaque. The posterior angular gyrus and
      the adjacent superior occipital gyrus had a high probability of connection with
      the parahippocampal gyrus. The projection pathway resembled the macaque inferior
      longitudinal fascicle, which connects these areas. The ventral premotor cortex
      had a high probability of connection with the supramarginal gyrus and anterior
      IPS. The connection was mediated by the third branch of the superior longitudinal
      fascicle, which interconnects similar regions in the macaque. Human parietal
      areas have anatomical connections resembling those of functionally related
      macaque parietal areas.

PMID- 16306321
TI  - V1 partially solves the stereo aperture problem.
AB  - If a bar stimulus extends beyond a cell's receptive field, then alterations in
      binocular disparity parallel to the bar's orientation leave the portion of the
      stimulus within the cell's receptive field unchanged. This makes it hard for the
      cell to respond correctly to the bar's disparity. Likening the cell's receptive
      field to an aperture through which the cell views the world, this issue has been
      called the "aperture problem" and is a specific form of the more general stereo
      correspondence problem. We found no cells in macaque primary visual cortex (V1)
      that, when faced with this situation, were sensitive to the disparity of the bar.
      However, we did find a number of cells that showed sensitivity to parallel
      disparity shifts, but these cells responded only to the ends of the long bar. The
      ability to respond selectively to such tracking features could be the first step
      towards solving the stereo aperture problem. The second step would require either
      that the disparity information that in V1 is associated only with the ends of the
      stimulus be associated with the rest of the stimulus or that subsequent stages of
      visual processing respond preferentially to the end-selective cells. As this
      second step does not appear to occur in V1, we conclude that V1 only partially
      solves the stereo aperture problem.

PMID- 16306322
TI  - Cortical connections of the inferior parietal cortical convexity of the macaque
      monkey.
AB  - We traced the cortical connections of the 4 cytoarchitectonic fields--Opt, PG,
      PFG, PF--forming the cortical convexity of the macaque inferior parietal lobule
      (IPL). Each of these fields displayed markedly distinct sets of connections.
      Although Opt and PG are both targets of dorsal visual stream and temporal visual
      areas, PG is also target of somatosensory and auditory areas. Primary parietal
      and frontal connections of Opt include area PGm and eye-related areas. In
      contrast, major parietal and frontal connections of PG include IPL, caudal
      superior parietal lobule (SPL), and agranular frontal arm-related areas. PFG is
      target of somatosensory areas and also of the medial superior temporal area (MST)
      and temporal visual areas and is connected with IPL, rostral SPL, and ventral
      premotor arm- and face-related areas. Finally, PF is primarily connected with
      somatosensory areas and with parietal and frontal face- and arm-related areas.
      The present data challenge the bipartite subdivision of the IPL convexity into a
      caudal and a rostral area (7a and 7b, respectively) and provide a new anatomical
      frame of reference of the macaque IPL convexity that advances our present
      knowledge on the functional organization of this cortical sector, giving new
      insight into its possible role in space perception and motor control.

PMID- 16306323
TI  - Neural correlates of the spontaneous phase transition during bimanual
      coordination.
AB  - Repetitive bimanual finger-tapping movements tend toward mirror symmetry: There
      is a spontaneous transition from less stable asymmetrical movement patterns to
      more stable symmetrical ones under frequency stress but not vice versa. During
      this phase transition, the interaction between the signals controlling each hand
      (cross talk) is expected to be prominent. To depict the regions of the brain in
      which cortical cross talk occurs during bimanual coordination, we conducted event
      related functional magnetic resonance imaging using a bimanual repetitive-tapping
      task. Transition-related activity was found in the following areas: the bilateral
      ventral premotor cortex, inferior frontal gyrus, middle frontal gyrus, inferior
      parietal lobule, insula, and thalamus; the right rostral portion of the dorsal
      premotor cortex and midbrain; the left cerebellum; and the presupplementary motor
      area, rostral cingulate zone, and corpus callosum. These regions were discrete
      from those activated by bimanual movement execution. The phase-transition-related
      activation was right lateralized in the prefrontal, premotor, and parietal
      regions. These findings suggest that the cortical neural cross talk occurs in the
      distributed networks upstream of the primary motor cortex through asymmetric
      interhemispheric interaction.

PMID- 16306324
TI  - Anatomical differences in the mirror neuron system and social cognition network
      in autism.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with
      impaired social and emotional skills, the anatomical substrate of which is still
      unknown. In this study, we compared a group of 14 high-functioning ASD adults
      with a group of controls matched for sex, age, intelligence quotient, and
      handedness. We used an automated technique of analysis that accurately measures
      the thickness of the cerebral cortex and generates cross-subject statistics in a
      coordinate system based on cortical anatomy. We found local decreases of gray
      matter in the ASD group in areas belonging to the mirror neuron system (MNS),
      argued to be the basis of empathic behavior. Cortical thinning of the MNS was
      correlated with ASD symptom severity. Cortical thinning was also observed in
      areas involved in emotion recognition and social cognition. These findings
      suggest that the social and emotional deficits characteristic of autism may
      reflect abnormal thinning of the MNS and the broader network of cortical areas
      subserving social cognition.

PMID- 16306325
TI  - Context influences early perceptual analysis of faces--an electrophysiological
      study.
AB  - Electrophysiological and hemodynamic correlates of processing isolated faces have
      been investigated extensively over the last decade. A question not addressed thus
      far is whether the visual scene, which normally surrounds a face or a facial
      expression, has an influence on how the face is processed. Here we investigated
      this issue by presenting faces in natural contexts and measuring whether the
      emotional content of the scene influences processing of a facial expression.
      Event-related potentials were recorded to faces (fearful/neutral) embedded in
      scene contexts (fearful/neutral) while participants performed an orientation
      decision task (face upright or inverted). Two additional experiments were run,
      one to examine the effects of context that occur without a face and the other to
      evaluate the effects of faces isolated from contexts. Faces without any context
      showed the largest N170 amplitudes. The presence of a face in a fearful context
      enhances the N170 amplitude over a face in neutral contexts, an effect that is
      strongest for fearful faces on left occipito-temporal sites. This N170 effect,
      and the corresponding topographic distribution, was not found for contexts-only,
      indicating that the increased N170 amplitude results from the combination of face
      and fearful context. These findings suggest that the context in which a face
      appears may influence how it is encoded.

PMID- 16306326
TI  - A tale of two cousins: type 1 and type 2 diabetes.

PMID- 16306327
TI  - Mechanisms of beta-cell death in type 2 diabetes.
AB  - A decrease in the number of functional insulin-producing beta-cells contributes
      to the pathophysiology of type 2 diabetes. Opinions diverge regarding the
      relative contribution of a decrease in beta-cell mass versus an intrinsic defect
      in the secretory machinery. Here we review the evidence that glucose,
      dyslipidemia, cytokines, leptin, autoimmunity, and some sulfonylureas may
      contribute to the maladaptation of beta-cells. With respect to these causal
      factors, we focus on Fas, the ATP-sensitive K+ channel, insulin receptor
      substrate 2, oxidative stress, nuclear factor-kappaB, endoplasmic reticulum
      stress, and mitochondrial dysfunction as their respective mechanisms of action.
      Interestingly, most of these factors are involved in inflammatory processes in
      addition to playing a role in both the regulation of beta-cell secretory function
      and cell turnover. Thus, the mechanisms regulating beta-cell proliferation,
      apoptosis, and function are inseparable processes.

PMID- 16306328
TI  - Association of systemic chemokine concentrations with impaired glucose tolerance
      and type 2 diabetes: results from the Cooperative Health Research in the Region
      of Augsburg Survey S4 (KORA S4).
AB  - Chemokines are crucial immune mediators in many physiological and
      pathophysiological conditions. Chemokines have been hypothesized to be involved
      in macrophage infiltration into adipose tissue in obesity and might therefore
      play an important role in the development of obesity-related disorders like type
      2 diabetes. Out of 1,653 individuals aged 55-74 years participating in a
      population-based survey in southern Germany (the Kooperative Gesundheitsforschung
      in der Region Augsburg [KORA] [Cooperative Health Research in the Region of
      Augsburg] Survey S4, 1999-2001), 236 individuals with type 2 diabetes, 242
      subjects with impaired glucose tolerance (IGT), and 244 normoglycemic control
      subjects were studied for circulating concentrations of interleukin (IL)-8;
      RANTES (regulated on activation, normal T-cell expressed, and secreted);
      interferon-gamma-inducible protein-10 (IP-10), and eotaxin. Systemic
      concentrations of RANTES were higher in individuals with IGT or type 2 diabetes
      than in control subjects, whereas IL-8 levels were elevated in type 2 diabetic
      patients only (P < 0.001 for all comparisons). IP-10 and eotaxin were not
      significantly associated with IGT or type 2 diabetes. Adjustment for age, sex,
      BMI, hypertension, LDL cholesterol, HDL cholesterol, uric acid, C-reactive
      protein, and IL-6 did not alter these findings. Our findings indicate that RANTES
      and IL-8 may be involved in the development of type 2 diabetes independent of
      metabolic syndrome-related risk factors and of each other. There is no general
      upregulation of chemokine production in type 2 diabetes, but rather an
      association of the disease with specific members of the chemokine family.

PMID- 16306329
TI  - Interleukin-6 and diabetes: the good, the bad, or the indifferent?
AB  - Inflammatory mechanisms play a key role in the pathogenesis of type 1 diabetes.
      Individuals who progress to type 2 diabetes display features of low-grade
      inflammation years in advance of disease onset. This low-grade inflammation has
      been proposed to be involved in the pathogenetic processes causing type 2
      diabetes. Mediators of inflammation such as tumor necrosis factor-alpha,
      interleukin (IL)-1beta, the IL-6 family of cytokines, IL-18, and certain
      chemokines have been proposed to be involved in the events causing both forms of
      diabetes. IL-6 has in addition to its immunoregulatory actions been proposed to
      affect glucose homeostasis and metabolism directly and indirectly by action on
      skeletal muscle cells, adipocytes, hepatocytes, pancreatic beta-cells, and
      neuroendocrine cells. Here we argue that IL-6 action-in part regulated by
      variance in the IL-6 and IL-6alpha receptor genes-contributes to, but is probably
      neither necessary nor sufficient for, the development of both type 1 and type 2
      diabetes. Thus, the two types of diabetes are also in this respect less apart
      than apparent. However, the mechanisms are not clear, and we therefore propose
      future directions for studies in this field.

PMID- 16306330
TI  - Environmental triggers and determinants of type 1 diabetes.
AB  - Type 1 diabetes is perceived as a chronic immune-mediated disease with a
      subclinical prodromal period characterized by selective loss of insulin-producing
      beta-cells in the pancreatic islets in genetically susceptible subjects. A series
      of evidence supports a critical role of exogenous factors in the development of
      type 1 diabetes, such as 1) the fact that <10% of individuals with HLA-conferred
      diabetes susceptibility do progress to clinical disease, 2) a pairwise
      concordance of type 1 diabetes of <40% among monozygotic twins, 3) a more than 10
      fold difference in the disease incidence among Caucasians living in Europe, 4) a
      several-fold increase in the incidence over the last 50 years, and 5) migration
      studies indicating that the disease incidence has increased in population groups
      who have moved from a low-incidence to a high-incidence region. This article
      discusses the trigger-booster hypothesis claiming that the diabetic disease
      process is triggered by an exogenous factor with definite seasonal variation and
      driven by one or several other environmental determinants. In addition, there are
      a series of modifying factors affecting the fate and pace of the process.
      Accordingly, progression to clinical type 1 diabetes typically requires the
      unfortunate combination of genetic disease susceptibility, a diabetogenic
      trigger, and a high exposure to a driving antigen.

PMID- 16306331
TI  - Psammomys obesus, a model for environment-gene interactions in type 2 diabetes.
AB  - Type 2 diabetes is characterized by insulin resistance and progressive beta-cell
      failure. Deficient insulin secretion, with increased proportions of insulin
      precursor molecules, is a common feature of type 2 diabetes; this could result
      from inappropriate beta-cell function and/or reduced beta-cell mass. Most studies
      using tissues from diabetic patients are retrospective, providing only limited
      information on the relative contribution of beta-cell dysfunction versus
      decreased beta-cell mass to the "beta-cell failure" of type 2 diabetes. The
      gerbil Psammomys obesus is a good model to address questions related to the role
      of insulin resistance and beta-cell failure in nutritionally induced diabetes.
      Upon a change from its natural low-calorie diet to the calorie-rich laboratory
      food, P. obesus develops moderate obesity associated with postprandial
      hyperglycemia. Continued dietary load, superimposed on its innate insulin
      resistance, results in depletion of pancreatic insulin stores, with increased
      proportions of insulin precursor molecules in the pancreas and the blood.
      Inadequate response of the preproinsulin gene to the increased insulin needs is
      an important cause of diabetes progression. Changes in beta-cell mass do not
      correlate with pancreatic insulin stores and are unlikely to play a role in
      disease initiation and progression. The major culprit is the inappropriate
      insulin production with depletion of insulin stores as a consequence. Similar
      mechanisms could operate during the evolution of type 2 diabetes in humans.

PMID- 16306332
TI  - Fetal and infant growth and glucose tolerance in the Hertfordshire Cohort Study:
      a study of men and women born between 1931 and 1939.
AB  - The Hertfordshire Cohort Study based in the U.K. was the first to report
      associations between fetal or infant growth and the prevalence of adult glucose
      intolerance and diabetes. Many studies have replicated the findings with respect
      to birth weight, but there have been fewer observations in relationship to infant
      growth, because this is infrequently recorded in routine datasets. Recently, we
      carried out glucose tolerance tests in a more recently born group of men and
      women from the Hertfordshire Cohort Study. The objective was to determine whether
      the associations with weights at birth and 1 year of age reported in the original
      study of people born between 1920 and 1930 were observed in people born between
      1931 and 1939. Birth weight was inversely related to the overall prevalence of
      diabetes (comprising newly diagnosed as well as existing cases) in men and women.
      However, weight at 1 year of age was not associated with diabetes in either sex.
      Analysis of data from the glucose tolerance tests showed that both sexes had
      evidence of higher insulin and glucose concentrations in people who were small at
      birth or during infancy. Finally, direct comparison of 2-h plasma glucose
      concentrations in the previous and current Hertfordshire study suggested that
      both surveys showed broad similarity of the trends in glucose tolerance with
      birth or infant weights; most differences arose at the extremes of the birth
      weight, possibly because of the small numbers of subjects studied in these
      groups.

PMID- 16306333
TI  - Mouse models and the genetics of diabetes: is there evidence for genetic overlap
      between type 1 and type 2 diabetes?
AB  - In humans, both type 1 and type 2 diabetes exemplify genetically heterogeneous
      complex diseases in which epigenetic factors contribute to underlying genetic
      susceptibility. Extended human pedigrees often show inheritance of both diabetes
      types. A common pathophysiological denominator in both disease forms is
      pancreatic beta-cell exposure to proinflammatory cytokines. Hence, it is
      intuitive that systemically expressed genes regulating beta-cell ability to
      withstand chronic diabetogenic stress may represent a component of shared
      susceptibility to both major disease forms. In this review, the authors assemble
      evidence from genetic experiments using animal models developing clearly distinct
      diabetes syndromes to inquire whether some degree of overlap in genes
      contributing susceptibility can be demonstrated. The conclusion is that although
      overlap exists in the pathophysiological insults leading to beta-cell destruction
      in the currently studied rodent models, the genetic bases seem quite distinct.

PMID- 16306334
TI  - Type 1 and type 2 diabetes: less apart than apparent? Proceedings of the Sixth
      Servier-IGIS Symposium. March 10-13, 2005. St. Jean Cap Ferrat, France.

PMID- 16306335
TI  - Class III alleles at the insulin VNTR polymorphism are associated with regulatory
      T-cell responses to proinsulin epitopes in HLA-DR4, DQ8 individuals.
AB  - A variable number of tandem repeats (VNTR) polymorphism upstream of the insulin
      promoter is strongly associated with type 1 diabetes. The short class I alleles
      are predisposing and the long class III alleles are protective. As a possible
      mechanism for this effect, we previously reported a two- to threefold higher
      insulin transcription from class III than from class I chromosomes in thymus
      where insulin is expressed at low levels, presumably for the purpose of self
      tolerance. In this article, we confirm this finding with independent methodology
      and report studies testing the hypothesis that class III alleles are associated
      with T-cell tolerance to (pro)insulin. Cytokine release in vitro after
      stimulation with 21 overlapping preproinsulin epitopes was assessed in blood
      mononuclear cells as well as naive and memory CD4+ T-cell subsets from 33
      individuals with the high-risk DRB1*04, DQ8 haplotype (12 type 1 diabetic
      patients, 11 healthy control subjects, and 10 autoantibody-positive subjects). No
      significant differences between genotypes (24 I/I subjects versus 10 I/III or
      III/III subjects) were observed for gamma-interferon, tumor necrosis factor
      alpha, or interleukin (IL)-4. By contrast, the I/III + III/III group showed a
      significant threefold higher IL-10 release in memory T-cells for whole proinsulin
      and the immunodominant region. Given that IL-10 is a marker of regulatory
      function, our data are consistent with the hypothesis that higher insulin levels
      in the thymus promote the formation of regulatory T-cells, a proposed explanation
      for the protective effect of the class III alleles.

PMID- 16306336
TI  - Natural history of type 1 diabetes.
AB  - The natural history of autoimmune type 1 diabetes in children is associated with
      the appearance of islet autoantibodies early in life, which is influenced by
      genetic and environmental factors. Once islet autoantibodies have developed, the
      progression to diabetes in antibody-positive individuals is determined by the age
      of antibody appearance and by the magnitude of the autoimmunity, in turn related
      to the age of the subject. Characteristics that describe the magnitude of the
      autoimmunity can stage progression to type 1 diabetes in islet autoantibody
      positive subjects regardless of genetic background or age.

PMID- 16306337
TI  - Natural history of beta-cell function in type 1 diabetes.
AB  - Despite extensive and ongoing investigations of the immune mechanisms of
      autoimmune diabetes in humans and animal models, there is much less information
      about the natural history of insulin secretion before and after the clinical
      presentation of type 1 diabetes and the factors that may affect its course.
      Studies of insulin production previously published and from the Diabetes
      Prevention Trial (DPT)-1 suggest that there is progressive impairment in insulin
      secretory responses but the reserve in response to physiological stimuli may be
      significant at the time of diagnosis, although maximal responses are more
      significantly impaired. Other factors, including insulin resistance, may play a
      role in the timing of clinical presentation along this continuum. The factors
      that predict the occurrence and rapidity of decline in beta-cell function are
      still largely unknown, but most studies have identified islet cell autoantibodies
      as predictors of future decline and age as a determinant of residual insulin
      production at diagnosis. Historical as well as recent clinical experience has
      emphasized the importance of residual insulin production for glycemic control and
      prevention of end-organ complications. Understanding the modifiers and predictors
      of beta-cell function would allow targeting immunological approaches to those
      individuals most likely to benefit from therapy.

PMID- 16306338
TI  - Characteristics of autoimmunity in type 1 diabetes and type 1.5 overlap with type
      2 diabetes.
AB  - This presentation is an overview of mechanisms for developing and maintaining
      self-tolerance in mammalian organisms. Because this meeting is focused on type 1
      diabetes and its mechanisms, the discussion deals primarily with mechanisms of T
      cell tolerance, since type 1 diabetes in both effector and initiator phases is
      primarily a T-cell-mediated autoimmune disease. Emphasis is placed on more
      recently discovered mechanisms of maintaining self-tolerance (autoimmune
      regulator [AIRE]) and a new defect in T-cell negative selection. The emerging
      picture is that of a polygenic disease with various combinations of different
      alleles of many genes with important roles in the normal immune response or
      normal immune responses.

PMID- 16306339
TI  - Type 1 and type 2 diabetes: what do they have in common?
AB  - Type 1 and type 2 diabetes frequently co-occur in the same families, suggesting
      common genetic susceptibility. Such mixed family history is associated with an
      intermediate phenotype of diabetes: insulin resistance and cardiovascular
      complications in type 1 diabetic patients and lower BMI and less cardiovascular
      complications as well as lower C-peptide concentrations in type 2 diabetic
      patients. GAD antibody positivity is more common in type 2 diabetic patients from
      mixed families than from common type 2 diabetes families. The mixed family
      history is associated with more type 1-like genetic (HLA and insulin gene) and
      phenotypic characteristics in type 2 diabetic patients, especially in the GAD
      antibody-positive subgroup. Leaving out the extreme ends of diabetes phenotypes,
      young children progressing rapidly to total insulin deficiency and strongly
      insulin-resistant subjects mostly with non-Europid ethnic origin, a large
      proportion of diabetic patients may have both type 1 and type 2 processes
      contributing to their diabetic phenotype.

PMID- 16306340
TI  - Dense core vesicle proteins IA-2 and IA-2beta: metabolic alterations in double
      knockout mice.
AB  - IA-2 and IA-2beta are members of the transmembrane protein tyrosine phosphatase
      family located in dense core vesicles of neuroendocrine cells, including the beta
      cells of pancreatic islets. In the present study, by mating C57BL/6Nci IA-2(+/-)
      with IA-2beta(+/-) mice, we generated double knockout mice (IA-2(-/-)/IA-2beta(-/
      )) to study the effect of the combined deletion of these two proteins on insulin
      secretion and blood glucose levels. The double knockout mice appeared healthy at
      birth and showed normal growth and development. Histological examination and
      immunostaining for insulin, glucagon, somatostatin, and pancreatic polypeptide
      revealed no difference between the double knockout and wild-type mice. Nonfasting
      blood glucose and insulin levels also were within the normal range. However,
      compared with the wild-type mice, the double knockout mice showed glucose
      intolerance and an absent first-phase insulin release curve. No evidence of
      insulin resistance was observed nor were there alterations in fasting blood
      glucose, insulin, or leptin levels in the double knockout mice maintained on a
      high-fat diet compared with the wild-type mice maintained on the same diet. In
      addition, to determine whether the combined deletion of IA-2 and IA-2beta played
      any role in the development of diabetes in NOD mice, we generated double knockout
      mice on the NOD/LtJ background. The incidence of diabetes in these mice was not
      significantly different than that in the wild-type mice. Taken together, our
      experiments show that the dense core vesicle proteins IA-2 and IA-2beta, alone or
      in combination, are involved in insulin secretion, but neither alone nor in
      combination are they required for the development of diabetes in NOD mice.

PMID- 16306341
TI  - Autoantibodies in diabetes.
AB  - Islet cell autoantibodies are strongly associated with the development of type 1
      diabetes. The appearance of autoantibodies to one or several of the autoantigens
      GAD65, IA-2, or insulin-signals an autoimmune pathogenesis of beta-cell killing.
      A beta-cell attack may be best reflected by the emergence of autoantibodies
      dependent on the genotype risk factors, isotype, and subtype of the
      autoantibodies as well as their epitope specificity. It is speculated that
      progression to beta-cell loss and clinical onset of type 1 diabetes is reflected
      in a developing pattern of epitope-specific autoantibodies. Although the
      appearance of autoantibodies does not follow a distinct pattern, the presence of
      multiple autoantibodies has the highest positive predictive value for type 1
      diabetes. In the absence of reliable T-cell tests, dissection of autoantibody
      responses in subjects of genetic risk should prove useful in identifying triggers
      of islet autoimmunity by examining seroconversion and maturation of the
      autoantibody response that may mark time to onset of type 1 diabetes. The
      complexity of the disease process is exemplified by multiple clinical phenotypes,
      including autoimmune diabetes masquerading as type 2 diabetes in youth and
      adults. Autoantibodies may also provide prognostic information in clinically
      heterogeneous patient populations when examined longitudinally.

PMID- 16306342
TI  - Is latent autoimmune diabetes in adults distinct from type 1 diabetes or just
      type 1 diabetes at an older age?
AB  - Diabetes is classified clinically into two types: type 1 and type 2 diabetes.
      Type 1 diabetes is an autoimmune diabetes, whereas, in contrast, type 2 diabetes
      is nonautoimmune. However, there is a group of phenotypic adult type 2 diabetic
      patients ( approximately 10%) who have islet autoantibodies similar to type 1
      diabetes. These patients are said to have latent autoimmune diabetes in adults
      (LADA) or type 1.5 diabetes. T-cells reacting with islet proteins have been
      demonstrated in type 1 and type 1.5 diabetic patients. In contrast, classic
      autoantibody-negative type 2 diabetic patients are also negative for T-cell
      responses to islet proteins. Therefore, we questioned whether type 1 and type 1.5
      diabetes are similar or different autoimmune diseases. We have investigated the
      immunological and metabolic differences between type 1, type 1.5, and classic
      type 2 diabetic patients. We have identified autoantibody differences,
      differences in islet proteins recognized by T-cells, and differences in insulin
      resistance. We have also identified a small group of patients who have T-cells
      responsive to islet proteins but who are autoantibody negative. These patients
      appear to be similar to type 1.5 patients in having decreased stimulated C
      peptide values. These immunological differences between type 1 and type 1.5
      diabetes suggest at least partially distinct disease processes.

PMID- 16306343
TI  - Latent autoimmune diabetes in adults: definition, prevalence, beta-cell function,
      and treatment.
AB  - Latent autoimmune diabetes in adults (LADA) is a disorder in which, despite the
      presence of islet antibodies at diagnosis of diabetes, the progression of
      autoimmune beta-cell failure is slow. LADA patients are therefore not insulin
      requiring, at least during the first 6 months after diagnosis of diabetes. Among
      patients with phenotypic type 2 diabetes, LADA occurs in 10% of individuals older
      than 35 years and in 25% below that age. Prospective studies of beta-cell
      function show that LADA patients with multiple islet antibodies develop beta-cell
      failure within 5 years, whereas those with only GAD antibodies (GADAs) or only
      islet cell antibodies (ICAs) mostly develop beta-cell failure after 5 years. Even
      though it may take up to 12 years until beta-cell failure occurs in some
      patients, impairments in the beta-cell response to intravenous glucose and
      glucagon can be detected at diagnosis of diabetes. Consequently, LADA is not a
      latent disease; therefore, autoimmune diabetes in adults with slowly progressive
      beta-cell failure might be a more adequate concept. In agreement with proved
      impaired beta-cell function at diagnosis of diabetes, insulin is the treatment of
      choice.

PMID- 16306344
TI  - Role of endoplasmic reticulum stress and c-Jun NH2-terminal kinase pathways in
      inflammation and origin of obesity and diabetes.
AB  - Metabolic and immune systems are the most fundamental requirements for survival,
      and many metabolic and immune response pathways or nutrient- and pathogen-sensing
      systems have been evolutionarily highly conserved. Consequently, metabolic and
      immune pathways are also highly integrated and interdependent. In the past
      decade, it became apparent that this interface plays a critical role in the
      pathogenesis of chronic metabolic diseases, particularly obesity and type 2
      diabetes. Importantly, the inflammatory component in obesity and diabetes is now
      firmly established with the discovery of causal links between inflammatory
      mediators, such as tumor necrosis factor (TNF)-alpha and insulin receptor
      signaling and the elucidation of the underlying molecular mechanisms, such as c
      Jun NH2-terminal kinase (JNK)- and inhibitor of nuclear factor-kappaB kinase
      mediated transcriptional and posttranslational modifications that inhibit insulin
      action. More recently, obesity-induced endoplasmic reticulum stress has been
      demonstrated to underlie the initiation of obesity-induced JNK activation,
      inflammatory responses, and generation of peripheral insulin resistance. This
      article will review the link between stress, inflammation, and metabolic disease,
      particularly type 2 diabetes, and discuss the mechanistic and therapeutic
      opportunities that emerge from this platform by focusing on JNK and endoplasmic
      reticulum stress responses.

PMID- 16306345
TI  - Multifaceted therapeutic approaches for a multigenic disease.
AB  - Diabetes is a severe chronic disease that affects approximately 200 million
      individuals worldwide, with extremely debilitating effects and considerably high
      health care costs. The two major classes of diabetes, known as type 1 (previously
      known as insulin-dependent or juvenile-onset diabetes) and type 2 (non-insulin
      dependent diabetes), share common symptoms such as hyperglycemia and the
      development of long-term complications, but they differ in many aspects,
      including their etiopathogenesis. New insights suggest that overlapping factors,
      formerly considered typical hallmarks of each specific type, can coexist in the
      same diabetic patient, making it difficult to support a sharp distinction between
      the two classes and, more importantly, to adopt appropriate therapeutic
      solutions. In type 1 and type 2 diabetic subjects, but even more in patients with
      combined types, multiple genetic factors play a role in determining
      susceptibility or resistance to the disease, and perhaps also the time of onset,
      the severity of the symptoms, the possibility of developing complications and,
      ultimately, the response to therapy. In this review, the therapeutic treatments
      currently under investigation, as well as the curative strategies envisioned for
      future applications, are reanalyzed considering the multifaceted and complex
      aspects of a continuum that can be just defined as "diabetes."

PMID- 16306346
TI  - Role of beta-cells in type 1 diabetes pathogenesis.
AB  - Whether autoimmunity results primarily from a defect of the immune system, target
      organ dysfunction, or both remains an open issue in most human autoimmune
      diseases. The highly multigenic background on which diabetes develops in the NOD
      mouse and in the human suggests that numerous gene variants associate in
      contributing to activation of autoimmunity to beta-cells. Both immune genes and
      islet-related genes are involved. The presence of beta-cells is required for
      initiation of diabetes autoimmunity to proceed. Available experiments in the NOD
      mouse and epidemiological evidence in the human point to proinsulin as a key
      autoantigen in diabetes. The functional importance of insulin, the high number of
      autoantigens characterized at different stages of diabetes, and their clustering
      within beta-cell subparticles point to the islet as a starting point in the
      initiation phase of the disease. Genes that direct the autoimmune reaction toward
      the beta-cell target, autoantigens that are recognized by autoreactive B- and T
      cells along the autoimmune process, the importance of beta-cells in the
      activation of autoreactive lymphocytes, and the expression level of key beta-cell
      molecules along diabetes development are successively considered in this review.

PMID- 16306347
TI  - Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many
      differences, few similarities.
AB  - Type 1 and type 2 diabetes are characterized by progressive beta-cell failure.
      Apoptosis is probably the main form of beta-cell death in both forms of the
      disease. It has been suggested that the mechanisms leading to nutrient- and
      cytokine-induced beta-cell death in type 2 and type 1 diabetes, respectively,
      share the activation of a final common pathway involving interleukin (IL)-1beta,
      nuclear factor (NF)-kappaB, and Fas. We review herein the similarities and
      differences between the mechanisms of beta-cell death in type 1 and type 2
      diabetes. In the insulitis lesion in type 1 diabetes, invading immune cells
      produce cytokines, such as IL-1beta, tumor necrosis factor (TNF)-alpha, and
      interferon (IFN)-gamma. IL-1beta and/or TNF-alpha plus IFN-gamma induce beta-cell
      apoptosis via the activation of beta-cell gene networks under the control of the
      transcription factors NF-kappaB and STAT-1. NF-kappaB activation leads to
      production of nitric oxide (NO) and chemokines and depletion of endoplasmic
      reticulum (ER) calcium. The execution of beta-cell death occurs through
      activation of mitogen-activated protein kinases, via triggering of ER stress and
      by the release of mitochondrial death signals. Chronic exposure to elevated
      levels of glucose and free fatty acids (FFAs) causes beta-cell dysfunction and
      may induce beta-cell apoptosis in type 2 diabetes. Exposure to high glucose has
      dual effects, triggering initially "glucose hypersensitization" and later
      apoptosis, via different mechanisms. High glucose, however, does not induce or
      activate IL-1beta, NF-kappaB, or inducible nitric oxide synthase in rat or human
      beta-cells in vitro or in vivo in Psammomys obesus. FFAs may cause beta-cell
      apoptosis via ER stress, which is NF-kappaB and NO independent. Thus, cytokines
      and nutrients trigger beta-cell death by fundamentally different mechanisms,
      namely an NF-kappaB-dependent mechanism that culminates in caspase-3 activation
      for cytokines and an NF-kappaB-independent mechanism for nutrients. This argues
      against a unifying hypothesis for the mechanisms of beta-cell death in type 1 and
      type 2 diabetes and suggests that different approaches will be required to
      prevent beta-cell death in type 1 and type 2 diabetes.

PMID- 16306348
TI  - Peripheral hyperinsulinemia promotes tau phosphorylation in vivo.
AB  - Cerebral insulin receptors play an important role in regulation of energy
      homeostasis and development of neurodegeneration. Accordingly, type 2 diabetes
      characterized by insulin resistance is associated with an increased risk of
      developing Alzheimer's disease. Formation of neurofibrillary tangles, which
      contain hyperphosphorylated tau, represents a key step in the pathogenesis of
      neurodegenerative diseases. Here, we directly addressed whether peripheral
      hyperinsulinemia as one feature of type 2 diabetes can alter in vivo cerebral
      insulin signaling and tau phosphorylation. Peripheral insulin stimulation rapidly
      increased insulin receptor tyrosine phosphorylation, mitogen-activated protein
      kinase and phosphatidylinositol (PI) 3-kinase pathway activation, and dose
      dependent tau phosphorylation at Ser202 in the central nervous system. Phospho
      FoxO1 and PI-3,4,5-phosphate immunostainings of brains from insulin-stimulated
      mice showed neuronal staining throughout the brain, not restricted to brain areas
      without functional blood-brain barrier. Importantly, in insulin-stimulated
      neuronal/brain-specific insulin receptor knockout mice, cerebral insulin receptor
      signaling and tau phosphorylation were completely abolished. Thus, peripherally
      injected insulin directly targets the brain and causes rapid cerebral insulin
      receptor signal transduction and site-specific tau phosphorylation in vivo,
      revealing new insights into the linkage of type 2 diabetes and neurodegeneration.

PMID- 16306349
TI  - Expression of inducible 6-phosphofructo-2-kinase/fructose-2,6
      bisphosphatase/PFKFB3 isoforms in adipocytes and their potential role in
      glycolytic regulation.
AB  - 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase) catalyzes the
      synthesis and degradation of fructose 2,6-bisphosphate (F2,6BP), which is a
      powerful activator of 6-phosphofructo-1-kinase, the rate-limiting enzyme of
      glycolysis. Four genes encode PFK-2/FBPase (PFKFB1-4), and an inducible isoform
      (iPFK-2/PFKFB3) has been found to mediate F2,6BP production in proliferating
      cells. We have investigated the role of iPFK-2/PFKFB3 and related isoforms in the
      regulation of glycolysis in adipocytes. Human visceral fat cells express PFKFB3
      mRNA, and three alternatively spliced isoforms of iPFK-2/PFKFB3 are expressed in
      the epididymal fat pad of the mouse. Forced expression of the iPFK-2/PFKFB3 in
      COS-7 cells resulted in increased glucose uptake and cellular F2,6BP content.
      Prolonged insulin treatment of 3T3-L1 adipocytes led to reduced PFKFB3 mRNA
      expression, and epididymal fat pads from db/db mice also showed decreased
      expression of PFKFB3 mRNA. Finally, anti-phospho-iPFK-2(Ser461) Western blotting
      revealed strong reactivity in insulin-treated 3T3-L1 adipocyte, suggesting that
      insulin induces the phosphorylation of PFKFB3 protein. These data expand the role
      of these structurally unique iPFK-2/PFKFB3 isoforms in the metabolic regulation
      of adipocytes.

PMID- 16306350
TI  - Peroxisome proliferator-activated receptor (PPAR)alpha activation increases
      adiponectin receptors and reduces obesity-related inflammation in adipose tissue:
      comparison of activation of PPARalpha, PPARgamma, and their combination.
AB  - We examined the effects of activation of peroxisome proliferator-activated
      receptor (PPAR)alpha, PPARgamma, and both of them in combination in obese
      diabetic KKAy mice and investigated the mechanisms by which they improve insulin
      sensitivity. PPARalpha activation by its agonist, Wy-14,643, as well as PPARgamma
      activation by its agonist, rosiglitazone, markedly improved insulin sensitivity.
      Interestingly, dual activation of PPARalpha and -gamma by a combination of Wy
      14,643 and rosiglitazone showed increased efficacy. Adipocyte size in Wy-14,643
      treated KKAy mice was much smaller than that of vehicle- or rosiglitazone-treated
      mice, suggesting that activation of PPARalpha prevents adipocyte hypertrophy.
      Moreover, Wy-14,643 treatment reduced inflammation and the expression of
      macrophage-specific genes in white adipose tissue (WAT). Importantly, Wy-14,643
      treatment upregulated expression of the adiponectin receptor (AdipoR)-1 and
      AdipoR2 in WAT, which was decreased in WAT of KKAy mice compared with that in
      nondiabetic control mice. Furthermore, Wy-14,643 directly increased expression of
      AdipoRs and decreased monocyte chemoattractant protein-1 expression in adipocytes
      and macrophages. Rosiglitazone increased serum adiponectin concentrations and the
      ratio of high molecular weight multimers of adiponectin to total adiponectin. A
      combination of rosiglitazone and Wy-14,643 increased both serum adiponectin
      concentrations and AdipoR expression in WAT. These data suggest that PPARalpha
      activation prevents inflammation in WAT and that dual activation of PPARalpha and
      -gamma enhances the action of adiponectin by increasing both adiponectin and
      AdipoRs, which can result in the amelioration of obesity-induced insulin
      resistance.

PMID- 16306351
TI  - A polygenic model of the metabolic syndrome with reduced circulating and intra
      adipose glucocorticoid action.
AB  - Despite major advances in understanding monogenic causes of morbid obesity, the
      complex genetic and environmental etiology of idiopathic metabolic syndrome
      remains poorly understood. One hypothesis suggests that similarities between the
      metabolic disease of plasma glucocorticoid excess (Cushing's syndrome) and
      idiopathic metabolic syndrome results from increased glucocorticoid
      reamplification within adipose tissue by 11beta-hydroxysteroid dehydrogenase type
      1 (11beta-HSD-1). Indeed, 11beta-HSD-1 is now a major therapeutic target. Because
      much supporting evidence for a role of adipose 11beta-HSD-1 comes from transgenic
      or obese rodents with single-gene mutations, we investigated whether the
      predicted traits of metabolic syndrome and glucocorticoid metabolism were
      coassociated in a unique polygenic model of obesity developed by long-term
      selection for divergent fat mass (Fat and Lean mice with 23 vs. 4% fat as body
      weight, respectively). Fat mice exhibited an insulin-resistant metabolic syndrome
      including fatty liver and hypertension. Unexpectedly, Fat mice had a marked intra
      adipose (11beta-HSD-1) and plasma glucocorticoid deficiency but higher liver
      glucocorticoid action. Furthermore, metabolic disease was exacerbated only in Fat
      mice when challenged with exogenous glucocorticoids or a high-fat diet. Our data
      suggest that idiopathic metabolic syndrome might associate with such a novel
      pattern of glucocorticoid action and sensitivity in humans, with implications for
      tissue-specific therapeutic targeting of 11beta-HSD-1.

PMID- 16306352
TI  - Whole-body insulin resistance in the absence of obesity in FVB mice with
      overexpression of Dgat1 in adipose tissue.
AB  - Insulin resistance is often associated with obesity. We tested whether
      augmentation of triglyceride synthesis in adipose tissue by transgenic
      overexpression of the diacylglycerol aclytransferase-1 (Dgat1) gene causes
      obesity and/or alters insulin sensitivity. Male FVB mice expressing the aP2-Dgat1
      had threefold more Dgat1 mRNA and twofold greater DGAT activity levels in adipose
      tissue. After 30 weeks of age, these mice had hyperglycemia, hyperinsulinemia,
      and glucose intolerance on a high-fat diet but were not more obese than wild-type
      littermates. Compared with control littermates, Dgat1 transgenic mice were both
      insulin and leptin resistant and had markedly elevated plasma free fatty acid
      levels. Adipocytes from Dgat1 transgenic mice displayed increased basal and
      isoproterenol-stimulated lipolysis rates and decreased gene expression for fatty
      acid uptake. Muscle triglyceride content was unaffected, but liver mass and
      triglyceride content were increased by 20 and 300%, respectively. Hepatic insulin
      signaling was suppressed, as evidenced by decreased phosphorylation of insulin
      receptor-beta (Tyr(1,131)/Tyr(1,146)) and protein kinase B (Ser473). Gene
      expression data suggest that the gluconeogenic enzymes, glucose-6-phosphatase and
      phosphoenolpyruvate carboxykinase, were upregulated. Thus, adipose overexpression
      of Dgat1 gene in FVB mice leads to diet-inducible insulin resistance, which is
      secondary to redistribution of fat from adipose tissue to the liver in the
      absence of obesity.

PMID- 16306353
TI  - Growth and functional maturation of beta-cells in implants of endocrine cells
      purified from prenatal porcine pancreas.
AB  - The development of islet cell transplantation as a cure for diabetes is limited
      by the shortage of human donor organs. Moreover, currently used grafts exhibit a
      marginal beta-cell mass with an apparently low capacity for beta-cell renewal and
      growth. Although duct-associated nonendocrine cells have often been suggested as
      a potential source for beta-cell production, recent work in mice has demonstrated
      the role of beta-cells in postnatal growth of the pancreatic beta-cell mass. The
      present study investigated whether the beta-cell mass can grow in implants that
      are virtually devoid of nonendocrine cells. Endocrine islet cells were purified
      from prenatal porcine pancreases (gestation >110 days) and implanted under the
      kidney capsule of nude mice. beta-Cells initially presented with signs of
      immaturity: small size, low insulin content, undetectable C-peptide release, and
      an inability to correct hyperglycemia. They exhibited a proliferative activity
      that was highest during posttransplant week 1 (2.6 and 5% bromodeoxyuridine
      [BrdU]-positive beta-cells 4 and 72 h posttransplant) and then decreased over 20
      weeks to rates measured in the pancreas (0.2% BrdU-positive cells). beta-Cell
      proliferation in implants first compensated for beta-cell loss during
      posttransplant week 1 and then increased the beta-cell number fourfold between
      posttransplant weeks 1 and 20. Rates of alpha-cell proliferation were only
      shortly and moderately increased, which explained the shift in cellular
      composition of the implant (beta-cell 40 vs. 90% and alpha-cell 40 vs. 7% at the
      start and posttransplant week 20, respectively). beta-Cells progressively matured
      during the 20 weeks after transplantation, with a twofold increase in cell
      volume, a sixfold increase in cellular insulin content, plasma C-peptide levels
      of 1-2 ng/ml, and an ability to correct diabetes. They became structurally
      organized as homogenous clusters with their secretory vesicles polarized toward
      fenestrated capillaries. We concluded that the immature beta-cell phenotype
      provides grafts with a marked potential for beta-cell growth and differentiation
      and hence may have a potential role in curing diabetes. Cells with this phenotype
      can be isolated from prenatal organs; their presence in postnatal organs needs to
      be investigated.

PMID- 16306354
TI  - On the edge of autoimmunity: T-cell stimulation by steady-state dendritic cells
      prevents autoimmune diabetes.
AB  - Targeting of antigens to immature dendritic cells has been shown to result in
      antigen-specific T-cell tolerance in vivo. In the INS-HA/TCR-HA transgenic mouse
      model for type 1 diabetes, we tested the potential of the dendritic cell-specific
      monoclonal antibody DEC-205 conjugated to the hemagglutinin (HA) antigen (DEC-HA)
      to prevent disease onset. Whereas untreated INS-HA/TCR-HA mice all develop
      insulitis, and approximately 40% of these mice become diabetic, repeated
      injection of newborn mice with DEC-HA protected almost all mice from disease
      development. Histological examination of the pancreata revealed significant
      reduction of peri-islet infiltrations in DEC-HA-treated mice, and the islet
      structure remained intact. Moreover, HA-specific CD4+ T-cells from anti-DEC-HA
      treated INS-HA/TCR-HA mice exhibited increased expression of Foxp3, cytotoxic T
      lymphocyte-associated antigen-4, and the immunosuppressive cytokines interleukin
      10 and transforming growth factor-beta. The findings indicate that targeting of
      the HA antigen to immature dendritic cells in vivo leads to a relative increase
      of antigen-specific Foxp3+ regulatory T-cells that suppress the development of
      type 1 diabetes. Our results provide a basis for the development of novel
      strategies focusing on prevention rather than treatment of autoimmune diseases.

PMID- 16306355
TI  - The HMG box transcription factor Sox4 contributes to the development of the
      endocrine pancreas.
AB  - To investigate the role of the Sry/hydroxymethylglutaryl box (Sox) transcription
      factors in the development of the pancreas, we determined the expression pattern
      of Sox factors in the developing mouse pancreas. By RT-PCR, we detected the
      presence of multiple Sox family members in both the developing pancreas and
      mature islets and then focused on two factors, Sox2 and Sox4. The expression
      field of Sox2, which plays a role in the maintenance of some stem cell
      populations, included the developing duodenum, but Sox2 was specifically excluded
      from the pancreatic buds. In contrast, Sox4 was detected broadly in the early
      pancreatic buds and eventually became restricted to the nuclei of all islet cells
      in the adult mouse. Mice homozygous for a null mutation of the sox4 gene showed
      normal pancreatic bud formation and endocrine cell differentiation up to
      embryonic day 12.5. Beyond that date, cultured pancreatic explants lacking sox4
      failed to form normal islets. Instead, a markedly reduced number of endocrine
      cells were found scattered through the explant. We show here that several Sox
      transcription factors are expressed in the developing pancreas and in the islet,
      and that one of these factors, Sox4, is required for the normal development of
      pancreatic islets.

PMID- 16306356
TI  - Inhibition of preproinsulin gene expression by leptin induction of suppressor of
      cytokine signaling 3 in pancreatic beta-cells.
AB  - Leptin inhibits insulin secretion and preproinsulin gene expression in pancreatic
      beta-cells, but signal transduction pathways and molecular mechanisms underlying
      this effect are poorly characterized. In this study, we analyzed leptin-mediated
      signal transduction and preproinsulin gene regulation at the molecular level in
      pancreatic beta-cells. Leptin stimulation led to janus kinase (JAK)2-dependent
      phosphorylation and nuclear translocation of the transcription factors signal
      transducer and activator of transcription (STAT)3 and STAT5b in INS-1 beta-cells.
      Leptin also induced mRNA expression of the JAK-STAT inhibitor suppressor of
      cytokine signaling (SOCS)3 in INS-1 beta-cells and human pancreatic islets in
      vitro and in pancreatic islets of ob/ob mice in vivo. Transcriptional activation
      of the rat SOCS3 promoter by leptin was observed with concomitant leptin-induced
      STAT3 and STAT5b DNA binding to specific promoter regions. Unexpectedly, SOCS3
      inhibited both basal and STAT3/5b-dependent rat preproinsulin 1 gene promoter
      activity in INS-1 cells. These results suggest that SOCS3 represents a
      transcriptional inhibitor of preproinsulin gene expression, which is induced by
      leptin through JAK-STAT3/5b signaling in pancreatic beta-cells. In conclusion,
      although SOCS3 is believed to be a negative feedback regulator of JAK-STAT
      signaling, our findings suggest involvement of SOCS3 in a direct gene regulatory
      pathway downstream of leptin-activated JAK-STAT signaling in pancreatic beta
      cells.

PMID- 16306357
TI  - Aspirin at low-intermediate concentrations protects retinal vessels in
      experimental diabetic retinopathy through non-platelet-mediated effects.
AB  - The prevention of diabetic retinopathy requires drugs that leverage the benefits
      of glycemic control without adding the burden of side effects. Aspirin at dosages
      of 1-1.5 g/day has prevented manifestations of diabetic retinal microangiopathy
      in a clinical trial as well as in studies with dogs. Because lower and safer
      doses of aspirin could be used if its beneficial effects on retinopathy were due
      to antithrombotic effects, we compared the effects of a selective antiplatelet
      drug (clopidogrel) to those of aspirin in streptozotocin-induced diabetic rats.
      Clopidogrel did not prevent neuronal apoptosis, glial reactivity, capillary cell
      apoptosis, or acellular capillaries in the retina of diabetic rats. Aspirin, at
      doses yielding serum levels (<0.6 mmol/l) well below the anti-inflammatory range
      for humans, prevented apoptosis of capillary cells and the development of
      acellular capillaries but did not prevent neuroglial abnormalities. The aldose
      reductase inhibitor sorbinil, used as the benchmark for the effect of the other
      drugs, prevented all abnormalities. The diabetic rat retina showed increased
      expression of the transcription factor CCAAT/enhancer-binding protein-beta, one
      of the known targets of low-intermediate concentrations of aspirin. Thus we found
      a spectrum of drug efficacy on the prevention of experimental diabetic
      retinopathy, ranging from the absent effect of a selective antiplatelet drug to
      the prevention of all abnormalities by an aldose reductase inhibitor. Aspirin at
      low-intermediate concentrations selectively prevented microangiopathy. The
      minimal effective dose of aspirin should now be sought.

PMID- 16306358
TI  - Glucose transporters in human renal proximal tubular cells isolated from the
      urine of patients with non-insulin-dependent diabetes.
AB  - The bulk of glucose that is filtered by the renal glomerulus is reabsorbed by the
      glucose transporters of the proximal convoluted tubular epithelium. However, it
      has been difficult to investigate this in diseases such as type 2 diabetes
      because of the inability to isolate primary renal cells from patients without a
      renal biopsy. We report here a method for the immunomagnetic isolation and novel
      primary culture of human exfoliated proximal tubular epithelial cells (HEPTECs)
      from fresh urine. The primary isolates are highly enriched and differentiated and
      express characteristic proximal tubular phenotypic markers. They continue to
      express the proximal tubular markers CD13/aminopeptidase-N, sodium glucose
      cotransporter (SGLT) 2, and alkaline phosphatase through up to six subsequent
      subcultures in a similar way to human proximal cells isolated from renal
      biopsies. In a hyperglycemic environment, HEPTECs isolated from patients with
      type 2 diabetes expressed significantly more SGLT2 and the facilitative glucose
      transporter GLUT2 than cells from healthy individuals. We also demonstrated a
      markedly increased renal glucose uptake in HEPTECs isolated from patients with
      type 2 diabetes compared with healthy control subjects. Our findings indicate for
      the first time in a human cellular model that increased renal glucose transporter
      expression and activity is associated with type 2 diabetes.

PMID- 16306359
TI  - Oxidative-nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in
      experimental diabetic neuropathy: the relation is revisited.
AB  - Poly(ADP-ribose) polymerase (PARP) activation, an important factor in the
      pathogenesis of diabetes complications, is considered a downstream effector of
      oxidative-nitrosative stress. However, some recent findings suggest that it is
      not necessarily the case and that PARP activation may precede and contribute to
      free radical and oxidant-induced injury. This study evaluated the effect of PARP
      inhibition on oxidative-nitrosative stress in diabetic peripheral nerve, vasa
      nervorum, aorta, and high glucose-exposed human Schwann cells. In vivo
      experiments were performed in control rats and streptozocin (STZ)-induced
      diabetic rats treated with and without the PARP inhibitor 3-aminobenzamide (ABA)
      (30 mg . kg(-1) . day(-1) i.p. for 2 weeks after 2 weeks of untreated diabetes).
      Human Schwann cells (HSC) (passages 7-10; ScienCell Research Labs) were cultured
      in 5.5 or 30 mmol/l glucose with and without 5 mmol/l ABA. Diabetes-induced
      increase in peripheral nerve nitrotyrosine immunoreactivity, epineurial vessel
      superoxide and nitrotyrosine immunoreactivities, and aortic superoxide production
      was reduced by ABA. PARP-1 (Western blot analysis) was abundantly expressed in
      HSC, and its expression was not affected by high glucose or ABA treatment. High
      glucose-induced superoxide production and overexpression of nitrosylated and
      poly(ADP-ribosyl)ated protein, chemically reduced amino acid-(4)-hydroxynonenal
      adducts, and inducible nitric oxide synthase were decreased by ABA. We concluded
      that PARP activation contributes to superoxide anion radical and peroxynitrite
      formation in peripheral nerve, vasa nervorum, and aorta of STZ-induced diabetic
      rats and high- glucose-exposed HSC. The relations between oxidative-nitrosative
      stress and PARP activation in diabetes are bi- rather than unidirectional, and
      PARP activation cannot only result from but also lead to free radical and oxidant
      generation.

PMID- 16306360
TI  - Molecular characterization of new selective peroxisome proliferator-activated
      receptor gamma modulators with angiotensin receptor blocking activity.
AB  - Selective peroxisome proliferator-activated receptor (PPAR) gamma modulation is a
      new pharmacological approach that, based on selective receptor-cofactor
      interactions and target gene regulation, should result in potent insulin
      sensitization in the absence of PPARgamma-mediated adverse effects. Here, we
      characterize two angiotensin receptor blockers (ARBs), telmisartan and
      irbesartan, as new selective PPAR modulators (SPPARMs). Analysis of PPARgamma
      protein conformation using protease protection showed that telmisartan directly
      interacts with the receptor, producing a distinct conformational change compared
      with a glitazone. Glutathione S-transferase pull-down and fluorescence resonance
      energy transfer assays revealed selective cofactor binding by the ARBs compared
      with glitazones with an attenuated release of the nuclear receptor corepressor
      and absence of transcriptional intermediary factor 2 recruitment by ARBs.
      Consistently, selective cofactor binding resulted in differential gene expression
      profiles in adipocytes (ARB versus glitazone treated) assessed by oligo
      microarray analysis. Finally, telmisartan improved insulin sensitivity in diet
      induced obese mice in the absence of weight gain. The present study identifies
      two ARBs as new SPPARMs. SPPARM activity by ARBs could retain the metabolic
      efficacy of PPARgamma activation with reduction in adverse effects exerting in
      parallel AT1 receptor blockade. This may provide a new therapeutic option for
      better cardiovascular risk management in metabolic diseases and may initiate the
      development of new classes of drugs combining potent antihypertensive and
      antidiabetic actions.

PMID- 16306361
TI  - Localization of Idd11 is not associated with thymus and nkt cell abnormalities in
      NOD mice.
AB  - Congenic mouse strains provide a unique resource for genetic dissection and
      biological characterization of chromosomal regions associated with diabetes
      progression in the nonobese diabetic (NOD) mouse. Idd11, a mouse diabetes
      susceptibility locus, was previously localized to a region on chromosome 4.
      Comparison of a panel of subcongenic NOD mouse strains with different intervals
      derived from the nondiabetic C57BL/6 (B6) strain now maps Idd11 to an
      approximately 8-Mb interval. B6-derived intervals protected congenic NOD mice
      from diabetes onset, even though lymphocytic infiltration of pancreatic islets
      was similar to that found in NOD mice. In addition, neither thymic structural
      irregularities nor NKT cell deficiencies were ameliorated in diabetes-resistant
      congenic NOD mice, indicating that Idd11 does not contribute to these
      abnormalities, which do not need to be corrected to prevent disease.

PMID- 16306362
TI  - Free fatty acids produce insulin resistance and activate the proinflammatory
      nuclear factor-kappaB pathway in rat liver.
AB  - To study mechanisms by which free fatty acids (FFAs) cause hepatic insulin
      resistance, we have used euglycemic-hyperinsulinemic clamping with and without
      infusion of lipid/heparin (to raise or to lower plasma FFAs) in alert male rats.
      FFA-induced hepatic insulin resistance was associated with increased hepatic
      diacylglycerol content (+210%), increased activities of two serine/threonine
      kinases (protein kinase C-delta and inhibitor of kappaB [IkappaB] kinase-beta),
      increased activation of the proinflammatory nuclear factor-kappaB (NF-kappaB)
      pathway (IkappaB kinase-beta, +640%; IkappaB-alpha, -54%; and NF-kappaB, +73%),
      and increased expression of inflammatory cytokines (tumor necrosis factor-alpha,
      +1,700% and interleukin-1beta, +440%) and plasma levels of monocyte
      chemoattractant protein-1 (+220%). We conclude that FFAs caused hepatic insulin
      resistance, which can produce overproduction of glucose and hyperglycemia, and
      initiated inflammatory processes in the liver that could potentially result in
      the development of steatohepatitis.

PMID- 16306363
TI  - Glucose metabolism in mice lacking muscle glycogen synthase.
AB  - Glycogen is an important component of whole-body glucose metabolism. MGSKO mice
      lack skeletal muscle glycogen due to disruption of the GYS1 gene, which encodes
      muscle glycogen synthase. MGSKO mice were 5-10% smaller than wild-type
      littermates with less body fat. They have more oxidative muscle fibers and, based
      on the activation state of AMP-activated protein kinase, more capacity to oxidize
      fatty acids. Blood glucose in fed and fasted MGSKO mice was comparable to wild
      type littermates. Serum insulin was lower in fed but not in fasted MGSKO animals.
      In a glucose tolerance test, MGSKO mice disposed of glucose more effectively than
      wild-type animals and had a more sustained elevation of serum insulin. This
      result was not explained by increased conversion to serum lactate or by enhanced
      storage of glucose in the liver. However, glucose infusion rate in a euglycemic
      hyperinsulinemic clamp was normal in MGSKO mice despite diminished muscle glucose
      uptake. During the clamp, MGSKO animals accumulated significantly higher levels
      of liver glycogen as compared with wild-type littermates. Although disruption of
      the GYS1 gene negatively affects muscle glucose uptake, overall glucose tolerance
      is actually improved, possibly because of a role for GYS1 in tissues other than
      muscle.

PMID- 16306364
TI  - Skeletal muscle insulin signaling defects downstream of phosphatidylinositol 3
      kinase at the level of Akt are associated with impaired nonoxidative glucose
      disposal in HIV lipodystrophy.
AB  - More than 40% of HIV-infected patients on highly active antiretroviral therapy
      (HAART) experience fat redistribution (lipodystrophy), a syndrome associated with
      insulin resistance primarily affecting insulin-stimulated nonoxidative glucose
      metabolism (NOGM(ins)). Skeletal muscle biopsies, obtained from 18 lipodystrophic
      nondiabetic patients (LIPO) and 18 nondiabetic patients without lipodystrophy
      (NONLIPO) before and during hyperinsulinemic (40 mU.m(-2).min(-1))-euglycemic
      clamps, were analyzed for insulin signaling effectors. All patients were on
      HAART. Both LIPO and NONLIPO patients were normoglycemic (4.9 +/- 0.1 and 4.8 +/-
      0.1 mmol/l, respectively); however, NOGM(ins) was reduced by 49% in LIPO patients
      (P < 0.001). NOGM(ins) correlated positively with insulin-stimulated glycogen
      synthase activity (I-form, P < 0.001, n = 36). Glycogen synthase activity (I
      form) correlated inversely with phosphorylation of glycogen synthase sites 2+2a
      (P < 0.001, n = 36) and sites 3a+b (P < 0.001, n = 36) during clamp. Incremental
      glycogen synthase-kinase-3alpha and -3beta phosphorylation was attenuated in LIPO
      patients (Ps < 0.05). Insulin-stimulated Akt Ser473 and Akt Thr308
      phosphorylation was decreased in LIPO patients (P < 0.05), whereas insulin
      receptor substrate-1-associated phosphatidylinositol (PI) 3-kinase activity
      increased significantly (P < 0.001) and similarly (NS) in both groups during
      clamp. Thus, low glycogen synthase activity explained impaired NOGM(ins) in HIV
      lipodystrophy, and insulin signaling defects were downstream of PI 3-kinase at
      the level of Akt. These results suggest mechanisms for the insulin resistance
      greatly enhancing the risk of type 2 diabetes in HIV lipodystrophy.

PMID- 16306365
TI  - Changes in exercise-induced gene expression in 5'-AMP-activated protein kinase
      gamma3-null and gamma3 R225Q transgenic mice.
AB  - 5'-AMP-activated protein kinase (AMPK) is important for metabolic sensing. We
      used AMPKgamma3 mutant-overexpressing Tg-Prkag3(225Q) and AMPKgamma3-knockout
      Prkag3-/- mice to determine the role of the AMPKgamma3 isoform in exercise
      induced metabolic and gene regulatory responses in skeletal muscle. Mice were
      studied after 2 h swimming or 2.5 h recovery. Exercise increased basal and
      insulin-stimulated glucose transport, with similar responses among genotypes. In
      Tg-Prkag3(225Q) mice, acetyl-CoA carboxylase (ACC) phosphorylation was increased
      and triglyceride content was reduced after exercise, suggesting that this
      mutation promotes greater reliance on lipid oxidation. In contrast, ACC
      phosphorylation and triglyceride content was similar between wild-type and Prkag3
      /- mice. Expression of genes involved in lipid and glucose metabolism was altered
      by genetic modification of AMPKgamma3. Expression of lipoprotein lipase 1,
      carnitine palmitoyl transferase 1b, and 3-hydroxyacyl-CoA dehydrogenase was
      increased in Tg-Prkag3(225Q) mice, with opposing effects in Prkag3-/- mice after
      exercise. GLUT4, hexokinase II (HKII), and glycogen synthase mRNA expression was
      increased in Tg-Prkag3(225Q) mice after exercise. GLUT4 and HKII mRNA expression
      was increased in wild-type mice and blunted in Prkag3-/- mice after recovery. In
      conclusion, the Prkag3(225Q) mutation, rather than presence of a functional
      AMPKgamma3 isoform, directly promotes metabolic and gene regulatory responses
      along lipid oxidative pathways in skeletal muscle after endurance exercise.

PMID- 16306366
TI  - The lack of beta-adrenoceptors results in enhanced insulin sensitivity in mice
      exhibiting increased adiposity and glucose intolerance.
AB  - We and others have previously shown that triple knockout mice lacking the
      beta1/beta2/beta3-adrenoceptors (beta-less mice) developed a progressive obesity
      at adulthood. Here, we studied the glucose homeostasis in beta-less mice before
      the onset of obesity. We show that beta-less mice have increased fat mass and are
      glucose intolerant. In addition, we observed that beta-less mice have impaired
      glucose-induced insulin secretion and exhibit an increase in liver PEPCK gene
      expression in the fed state, suggesting that they have increased gluconeogenesis.
      Although these characteristics are usually associated with insulin resistance,
      beta-less mice exhibit enhanced insulin sensitivity during insulin tolerance
      tests. This is keeping with the results obtained during euglycemic
      hyperinsulinemic clamps showing that beta-less mice display increased insulin
      responsiveness with normal suppression of hepatic glucose production. Altogether,
      our results suggest that an intact beta-adrenergic system is required to regulate
      overall glucose homeostasis and, in particular, insulin-mediated glucose uptake,
      most likely at the level of muscles and adipose tissue.

PMID- 16306367
TI  - Plasma free fatty acids and peroxisome proliferator-activated receptor alpha in
      the control of myocardial uncoupling protein levels.
AB  - Diabetic patients have abnormal cardiac energy metabolism associated with high
      plasma free fatty acid (FFA) concentrations. We investigated whether high plasma
      FFAs increase mitochondrial uncoupling protein (UCP) levels in the mouse heart by
      activating the nuclear transcription factor peroxisome proliferator-activated
      receptor (PPAR)alpha. We used Western blotting to measure UCP protein levels in
      isolated cardiac mitochondria from PPARalpha-/- and diabetic mice. Cardiac UCP2
      and UCP3 were significantly lower in the PPARalpha-/- mouse than in the wild
      type. Treatment with the PPARalpha-specific agonist, WY-14,643, increased cardiac
      UCP2 and UCP3 levels in wild-type mice but did not alter UCP levels in PPARalpha
      /- mice. Inhibition of beta-oxidation with etomoxir increased cardiac UCP2 and
      UCP3 levels in wild-type mice and UCP2 levels in PPARalpha-/- mice but did not
      alter UCP3 levels in PPARalpha-/- mice. Streptozotocin treatment, which increased
      circulating FFAs by 91%, did not alter cardiac UCP2 levels in wild-type or
      PPARalpha-/- mice but increased UCP3 levels in wild-type, and not in PPARalpha-/
      , mice. The diabetic db/db mouse had 50% higher plasma FFA concentrations and
      elevated cardiac UCP2 and UCP3 protein levels. We conclude that high plasma FFAs
      activated PPARalpha to increase cardiac UCP3 levels, but cardiac UCP2 levels
      changed via PPARalpha-dependent and -independent mechanisms.

PMID- 16306368
TI  - Decreased fat mass in interleukin-1 receptor antagonist-deficient mice: impact on
      adipogenesis, food intake, and energy expenditure.
AB  - Interleukin (IL)-1 is a regulator of inflammation but is also implicated in the
      control of energy homeostasis. Because the soluble IL-1 receptor antagonist (IL
      1Ra) is markedly increased in the serum of obese patients and is overexpressed in
      white adipose tissue in obesity, we studied the metabolic consequences of genetic
      IL-1Ra ablation in mice. We have shown that IL-1Ra-/- mice have a lean phenotype
      due to decreased fat mass, related to a defect in adipogenesis and increased
      energy expenditure. The adipocytes were smaller in these animals, and the
      expression of genes involved in adipogenesis was reduced. Energy expenditure as
      measured by indirect calorimetry was elevated, and weight loss in response to a
      24-h fast was increased in IL-1Ra-/- animals compared with wild-type mice. Lipid
      oxidation of IL-1Ra-/- mice was higher during the light period, reflecting their
      reduction in diurnal food intake. Interestingly, IL-1Ra-/- and IL-1Ra+/- mice
      presented an attenuation in high-fat diet-induced caloric hyperphagia, indicating
      a better adaptation to hypercaloric alimentation, which is in line with the role
      of IL-1Ra as a mediator of leptin resistance. Taken together, we show that IL-1Ra
      is an important regulator of adipogenesis, food intake, and energy expenditure.

PMID- 16306369
TI  - Resistance to diet-induced obesity in mu-opioid receptor-deficient mice: evidence
      for a "thrifty gene".
AB  - Using pharmacological tools, a role for opioid receptors in the regulation of
      food intake has been documented. However, the involvement of specific receptor
      subtypes remains questionable, and little information is available regarding a
      role for opioid receptors in energy metabolism. Using adult male mice lacking the
      mu-opioid receptor (MOR) gene (MOR-/-), we show that the MOR is not essential for
      the maintenance of normal levels of ad libitum food intake but does modulate the
      efficiency of energy storage during high-fat diets through the regulation of
      energy partitioning. When fed a regular diet, MOR-/- mice displayed only subtle
      alterations in energy homeostasis, suggesting a relative overuse of fat as a fuel
      source in the fed state. When fed a high-fat diet, MOR-/- mice were resistant to
      obesity and impaired glucose tolerance, despite having similar energy intake to
      wild-type mice. This resistance to obesity was associated with a strong induction
      of the expression of key mitochondrial enzymes involved in fatty acid oxidation
      within skeletal muscle. This metabolic role of the MOR, which is consistent with
      the properties of a "thrifty gene," suggests that the MOR pathway is a potential
      target for pharmacological intervention in the treatment of obesity associated
      with the intake of fatty diets.

PMID- 16306370
TI  - Individual mice can be distinguished by the period of their islet calcium
      oscillations: is there an intrinsic islet period that is imprinted in vivo?
AB  - Pulsatile insulin secretion in vivo is believed to be derived, in part, from the
      intrinsic glucose-dependent intracellular calcium concentration ([Ca2+]i)
      pulsatility of individual islets. In isolation, islets display fast, slow, or
      mixtures of fast and slow [Ca2+]i oscillations. We show that the period of islet
      [Ca2+]i oscillations is unique to each mouse, with the islets from an individual
      mouse demonstrating similar rhythms to one another. Based on their rhythmic
      period, mice were broadly classified as being either fast (0.65 +/- 0.1 min; n =
      6 mice) or slow (4.7 +/- 0.2 min; n = 15 mice). To ensure this phenomenon was not
      an artifact of islet-to-islet communication, we confirmed that islets cultured in
      isolation (period: 2.9 +/- 0.1 min) were not statistically different from islets
      cultured together from the same mouse (3.1 +/- 0.1 min, P > 0.52, n = 5 mice). We
      also compared pulsatile insulin patterns measured in vivo with islet [Ca2+]i
      patterns measured in vitro from six mice. Mice with faster insulin pulse periods
      corresponded to faster islet [Ca2+]i patterns, whereas slower insulin patterns
      corresponded to slower [Ca2+]i patterns, suggesting that the insulin rhythm of
      each mouse is preserved to some degree by its islets in vitro. We propose that
      individual mice have characteristic oscillatory [Ca2+]i patterns, which are
      imprinted in vivo through an unknown mechanism.

PMID- 16306371
TI  - Rho guanosine diphosphate-dissociation inhibitor plays a negative modulatory role
      in glucose-stimulated insulin secretion.
AB  - Extant studies have implicated the Rho subfamily of guanosine triphosphate
      binding proteins (G-proteins; e.g., Rac1) in physiological insulin secretion from
      isolated beta-cells. However, very little is known with regard to potential
      regulation by G-protein regulatory factors (e.g., the guanosine diphosphate
      dissociation inhibitor [GDI]) of insulin secretion from the islet beta-cell. To
      this end, using Triton X-114 phase partition, co-immunoprecipitation, and sucrose
      density gradient centrifugation approaches, we report coexistence of GDI with
      Rac1 in insulin-secreting beta-cells (INS cells). Overexpression of wild-type GDI
      significantly inhibited glucose-induced, but not KCl- or mastoparan-induced,
      insulin secretion from INS cells. Furthermore, glucose-stimulated insulin
      secretion (GSIS) was significantly increased in INS cells in which expression of
      GDI was inhibited via the small interfering RNA-mediated knockdown approach.
      Together, these data appear to suggest an inhibitory role for GDI in the glucose
      metabolic signaling cascade, which may be relevant for GSIS.

PMID- 16306372
TI  - Unraveling the temporal pattern of diet-induced insulin resistance in individual
      organs and cardiac dysfunction in C57BL/6 mice.
AB  - Type 2 diabetes is a heterogeneous disease characterized by insulin resistance
      and altered glucose and lipid metabolism in multiple organs. To understand the
      complex series of events that occur during the development of obesity-associated
      diabetes, we examined the temporal pattern of changes in insulin action and
      glucose metabolism in individual organs during chronic high-fat feeding in
      C57BL/6 mice. Insulin-stimulated cardiac glucose metabolism was significantly
      reduced after 1.5 weeks of high-fat feeding, and cardiac insulin resistance was
      associated with blunted Akt-mediated insulin signaling and GLUT4 levels. Insulin
      resistance in skeletal muscle, adipose tissue, and liver developed in parallel
      after 3 weeks of high-fat feeding. Diet-induced whole-body insulin resistance was
      associated with increased circulating levels of resistin and leptin but unaltered
      adiponectin levels. High-fat feeding caused insulin resistance in skeletal muscle
      that was associated with significantly elevated intramuscular fat content. In
      contrast, diet-induced hepatic insulin resistance developed before a marked
      increase in intrahepatic triglyceride levels. Cardiac function gradually declined
      over the course of high-fat feeding, and after 20 weeks of high-fat diet, cardiac
      dysfunction was associated with mild hyperglycemia, hyperleptinemia, and reduced
      circulating adiponectin levels. Our findings demonstrate that cardiac insulin
      resistance is an early adaptive event in response to obesity and develops before
      changes in whole-body glucose homeostasis. This suggests that obesity-associated
      defects in cardiac function may not be due to insulin resistance per se but may
      be attributable to chronic alteration in cardiac glucose and lipid metabolism and
      circulating adipokines.

PMID- 16306373
TI  - Nonalcoholic fatty liver disease and risk of future cardiovascular events among
      type 2 diabetic patients.
AB  - Nonalcoholic fatty liver disease (NAFLD) is closely correlated to several
      metabolic syndrome features. We assessed prospectively whether NAFLD predicts
      future cardiovascular disease (CVD) events among type 2 diabetic individuals,
      independent of metabolic syndrome features and other classical risk factors. We
      carried out a prospective nested case-control study in 2,103 type 2 diabetic
      patients who were free of diagnosed CVD at baseline. During 5 years of follow-up,
      248 participants (case subjects) subsequently developed nonfatal coronary heart
      disease (myocardial infarction and coronary revascularization procedures),
      ischemic stroke, or cardiovascular death. Using risk-set sampling, 496 patients
      (control subjects) among those who remained free of diagnosed CVD during follow
      up were randomly selected in a 2:1 ratio, matched for age and sex to the case
      subjects. After adjustment for age, sex, smoking history, diabetes duration,
      HbA1c, LDL cholesterol, liver enzymes, and use of medications, the presence of
      NAFLD was significantly associated with an increased CVD risk (odds ratio 1.84,
      95% CI 1.4-2.1, P < 0.001). Additional adjustment for the metabolic syndrome (as
      defined by National Cholesterol Education Program Adult Treatment Panel III
      criteria) appreciably attenuated, but did not abolish, this association (1.53,
      1.1-1.7, P = 0.02). In conclusion, NAFLD is significantly associated with a
      moderately increased CVD risk among type 2 diabetic individuals. This
      relationship is independent of classical risk factors and is only partly
      explained by occurrence of metabolic syndrome.

PMID- 16306374
TI  - Polymorphisms in IGF-binding protein 1 are associated with impaired renal
      function in type 2 diabetes.
AB  - The dysregulation of the IGF system has been implicated in the pathogenesis of
      obesity, diabetes, and diabetes complications such as nephropathy, but little is
      known about the genomics of the IGF system in health and disease. We genotyped 13
      single nucleotide polymorphisms (SNPs) in IGFBP1 gene in 732 representative type
      2 diabetic patients from the Salford Diabetes Register. Of the 13 SNPs, 8 were
      polymorphic and 7 of those had minor allele frequencies >0.1, one of which was in
      the gene promoter and one of which was nonsynonymous in exon 4. The minor alleles
      of these SNPs and two others were associated with a reduced prevalence of
      diabetic nephropathy. Haplotype analysis revealed that 97% of the genetic
      variation for IGFBP1 in the population sample could be accounted for using two of
      the "reno-protective" SNPs, with other SNPs adding little extra information. One
      of these two SNPs was the nonsynonymous mutation in exon 4, lying close to the
      integrin-binding RGD motif, which is thought to affect tissue delivery of IGF-I
      by IGF-binding protein 1 (IGFBP-1), possibly suggesting a "reno-protective"
      effect via altered IGFBP-1 binding. In conclusion, we have described the first
      genomic markers to be associated with diabetic microvascular complications within
      the human IGFBP1 gene.

PMID- 16306375
TI  - Plasma cholesteryl ester transfer is a determinant of intima-media thickness in
      type 2 diabetic and nondiabetic subjects: role of CETP and triglycerides.
AB  - We tested whether carotid artery intima-media thickness (IMT) is associated with
      plasma cholesteryl ester transfer (CET) and/or the plasma cholesteryl ester
      transfer protein (CETP) concentration in type 2 diabetic and control subjects. In
      87 male and female subjects with type 2 diabetes (nonsmokers, no insulin or lipid
      lowering drug treatment) and 82 control subjects, IMT, plasma CET, CETP mass, and
      lipids were determined. HDL cholesterol was lower, whereas IMT, pulse pressure,
      plasma triglycerides, and plasma CET and CETP concentration were higher in
      diabetic patients versus control subjects. In diabetic patients, plasma CET was
      positively determined by triglycerides (P < 0.001), non-HDL cholesterol (P <
      0.001), CETP (P = 0.002), and the interaction between CETP and triglycerides (P =
      0.004). In control subjects, plasma CET was positively related to triglycerides
      (P < 0.001) and non-HDL cholesterol (P < 0.001). HDL cholesterol was inversely
      related to plasma CET in each group (P < 0.01 for both). IMT was positively
      associated with plasma CET in diabetic (P = 0.05) and control (P < 0.05) subjects
      after adjustment for age, sex, and pulse pressure. No independent relationship
      with plasma CETP mass was found. Plasma CET is a positive determinant of IMT.
      Plasma CETP mass, in turn, is a determinant of CET with an increasing effect at
      higher triglycerides. These data, therefore, provide a rationale to evaluate the
      effects of CETP inhibitor treatment on plasma CET and on cardiovascular risk in
      diabetes-associated hypertriglyceridemia.

PMID- 16306376
TI  - A functional variant in the human betacellulin gene promoter is associated with
      type 2 diabetes.
AB  - Betacellulin (BTC) plays an important role in differentiation, growth, and
      antiapoptosis of pancreatic beta-cells. We characterized about 2.3 kb of the 5'
      flanking region of human BTC gene and identified six polymorphisms (-2159A>G, 
      1449G>A, -1388C>T, -279C>A, -233G>C, and -226A>G). The G allele in the -226A>G
      polymorphism was more frequent in type 2 diabetic patients (n = 250) than in
      nondiabetic subjects (n = 254) (35.6% vs. 27.8%, P = 0.007), and the -2159G, 
      1449A, and -1388T alleles were in complete linkage disequilibrium with the -226G
      allele. The frequencies of the -279A and -233C alleles were low (7.0 and 2.0% in
      diabetic patients), and no significant differences were observed. In the diabetic
      group, insulin secretion ability, assessed by the serum C-peptide response to
      intravenous glucagon stimulation, was lower in patients with the -226G allele
      (G/G, 2.96 +/- 0.16 ng/ml; G/A, 3.65 +/- 0.18 ng/ml; A/A, 3.99 +/- 0.16 ng/ml at
      5 min after stimulation; P = 0.008). Furthermore, in vitro functional analyses
      indicated that both the -226G and the -233C alleles caused an approximately 50%
      decrease in the promoter activity, but no effects of the -2159A>G, -1449G>A, 
      1388C>T, and -279C>A polymorphisms were observed. These results suggest that the 
      226A/G polymorphism of the BTC gene may contribute to the development of
      diabetes.

PMID- 16306377
TI  - HFE genetic variability, body iron stores, and the risk of type 2 diabetes in
      U.S. women.
AB  - To determine whether the HFE gene variants H63D and C282Y are associated with
      body iron stores and the risk of type 2 diabetes, we conducted a nested case
      control study of 714 incident cases of type 2 diabetes and 1,120 matching control
      subjects in a prospective cohort, the Nurses' Health Study. In both healthy
      control and diabetic case subjects, H63D homozygosity, C282Y, and the compound
      heterozygotes were associated with significantly higher levels of plasma ferritin
      and significantly lower ratios of transferrin receptors to ferritin. Such effects
      were independent of age, BMI, and lifestyle factors. Overall, there were no
      significant differences in genotypes of H63D and C282Y between the case and
      control subjects. A meta-analysis of 4,245 case and 5,982 control subjects
      indicated a null association of C282Y with diabetes risk, whereas carriers of
      H63D or the compound heterozygotes had marginally increased risk (odds ratio [OR]
      1.11 [95% CI 1.00-1.25] and 1.60 [0.99-2.60], respectively). In addition, we
      found a significant interaction between HFE variants and heme iron intake (P for
      interaction = 0.029). The ORs of type 2 diabetes across increasing quartiles of
      heme iron were 1.00, 1.21 (0.72-2.01), 1.72 (1.03-2.88), and 1.49 (0.91-2.46)
      among the participants with either the H63D or C282Y variant, whereas the ORs
      were 1.00, 0.71 (0.49-1.05), 1.12 (0.76-1.66), and 0.96 (0.65-1.42) among those
      with wild-type genotypes. Our data indicate significant effects of H63D and C282Y
      on body iron stores and suggest a potential interaction between HFE genotypes and
      heme iron intake in relation to the risk of type 2 diabetes.

PMID- 16306378
TI  - Patterns of linkage disequilibrium in the type 2 diabetes gene calpain-10.
AB  - We investigated the patterns and extent of linkage disequilibrium (LD) in the
      vicinity of the type 2 diabetes gene calapin-10 (CAPN10) in Mexican Americans,
      European Americans, African Americans, and Chinese Americans. We found that
      CAPN10 occurs within a single block of high LD and that LD decays rapidly outside
      of the gene. This reduces the likelihood that associations between CAPN10
      polymorphisms and type 2 diabetes could be attributed to variation at some
      distance from CAPN10. We also consistently observed that cases have more
      extensive LD than control subjects and that cases from families with evidence for
      linkage have more extensive LD than cases from families without evidence for
      linkage. These observations further suggest that there are one or more relatively
      common alleles increasing risk of type 2 diabetes in this local region.

PMID- 16306379
TI  - Insulin resistance syndrome in subjects with mutated RING finger protein TRIM37.
AB  - We evaluated the glucose and lipid metabolism in 65 patients (aged 1.1-55 years)
      with mulibrey (muscle-liver-brain-eye) nanism (MUL), which is a monogenic
      disorder with prenatal-onset growth failure and typical clinical characteristics.
      MUL is caused by mutations in the TRIM37 gene, encoding a peroxisomal protein
      (TRIM37) with E3 ubiquitin-ligase activity. The subjects underwent clinical
      evaluation, abdominal ultrasonography, and laboratory measurements, including a 3
      h oral glucose tolerance test. The results showed a dramatic change in glucose
      and lipid metabolism with age in MUL subjects. While the children had low fasting
      glucose and insulin levels, 90% of the adults had high fasting and postload
      insulin values (up to 1,450 mU/l). A 10-fold decrease in the fasting glucose-to
      insulin ratio and a 4-fold decrease in whole-body insulin sensitivity index were
      observed. Insulin resistance, fatty liver, high serum leptin, hypertension, and
      acantosis nigricans were already evident in many slim prepubertal children. Half
      of the adults had type 2 diabetes, and an additional 42% showed impaired glucose
      tolerance. Seventy percent fulfilled the National Cholesterol Education Program
      criteria for metabolic syndrome. The peroxisomal targeting and the functional
      link of TRIM37 to the ubiquitin-proteosome pathway may provide novel clues to the
      development of metabolic syndrome.

PMID- 16306380
TI  - Genetic heterogeneity in association of the SUMO4 M55V variant with
      susceptibility to type 1 diabetes.
AB  - Association studies are a potentially powerful approach to identifying
      susceptibility variants for common multifactorial diseases such as type 1
      diabetes, but the results are not always consistently reproducible. The IDDM5
      locus has recently been narrowed to an approximately 200-kb interval on
      chromosome 6q25 by two independent groups. These studies demonstrated that
      alleles at markers in the mitogen-activating protein kinase 7 interacting protein
      2 (MAP3K7IP2)/SUMO4 region were associated with susceptibility to type 1
      diabetes. Subsequent studies, however, showed inconsistency in the association of
      the SUMO4 gene with type 1 diabetes. To clarify the contribution of the M55V
      polymorphism of the SUMO4 gene to type 1 diabetes susceptibility, 541 type 1
      diabetic patients and 768 control subjects were studied in Asian populations. The
      M55V polymorphism was significantly associated with type 1 diabetes in Asian
      populations (summary odds ratio [OR] 1.46, P = 0.00083, Mantel-Haenszel test).
      Meta-analysis of published studies and the present data confirmed a highly
      significant association in Asian populations (summary OR 1.29, P = 7.0 x 10(-6))
      but indicated heterogeneity in the genetic effect of the SUMO4/MAP3K7IP2 locus on
      type 1 diabetes among diverse ethnic groups. These data indicate that the
      MAP3K7IP2/SUMO4 locus in the IDDM5 interval is associated with type 1 diabetes in
      Asian populations.

PMID- 16306381
TI  - Single nucleotide polymorphisms in the peroxisome proliferator-activated receptor
      delta gene are associated with skeletal muscle glucose uptake.
AB  - The peroxisome proliferator-activated receptors (PPARs) belong to a superfamily
      of nuclear receptors. It includes PPAR-delta, a key regulator of fatty acid
      oxidation and energy uncoupling, universally expressed in different tissues. The
      PPAR-delta gene (PPARD) maps to 6p21.2-p21.1 and has 11 exons and spans 35 kbp.
      We investigated the effects of single nucleotide polymorphisms (SNPs) of PPARD on
      whole-body, skeletal muscle, and subcutaneous adipose tissue glucose uptake in
      129 healthy individuals using the hyperinsulinemic-euglycemic clamp technique
      combined with fluorine-18-labeled fluorodeoxyglucose ([18F]FDG) and positron
      emission tomography (PET). Three of six SNPs of PPARD and their haplogenotypes
      were significantly associated with whole-body insulin sensitivity. [18F]FDG-PET
      scanning indicated that SNPs of PPARD primarily affected insulin sensitivity by
      modifying glucose uptake in skeletal muscle but not in adipose tissue. Our
      results give evidence that SNPs of PPARD regulate insulin sensitivity
      particularly in skeletal muscle.

PMID- 16306382
TI  - Mechanisms of hypoglycemia-associated autonomic failure and its component
      syndromes in diabetes.
AB  - Iatrogenic hypoglycemia is a problem for people with diabetes. It causes
      recurrent morbidity, and sometimes death, as well as a vicious cycle of recurrent
      hypoglycemia, precluding maintenance of euglycemia over a lifetime of diabetes.
      Improved therapeutic approaches that will minimize both hypo- and hyperglycemia
      will be based on insight into the pathophysiology of glucoregulation,
      specifically glucose counterregulation, in insulin-deficient (type 1 and advanced
      type 2) diabetes. In such patients, hypoglycemia is the result of the interplay
      of relative or absolute therapeutic insulin excess and compromised physiological
      (the syndrome of defective glucose counterregulation) and behavioral (the
      syndrome of hypoglycemia unawareness) defenses against falling plasma glucose
      concentrations. The concept of hypoglycemia-associated autonomic failure (HAAF)
      in diabetes posits that recent antecedent iatrogenic hypoglycemia causes both
      defective glucose counterregulation (by reducing epinephrine responses to a given
      level of subsequent hypoglycemia in the setting of absent decrements in insulin
      and absent increments in glucagon) and hypoglycemia unawareness (by reducing
      sympathoadrenal and the resulting neurogenic symptom responses to a given level
      of subsequent hypoglycemia) and thus a vicious cycle of recurrent hypoglycemia.
      The clinical impact of HAAF is well established in type 1 diabetes; it also
      affects those with advanced type 2 diabetes. It is now known to be largely
      reversible, by as little as 2-3 weeks of scrupulous avoidance of hypoglycemia, in
      most affected patients. However, the mechanisms of HAAF and its component
      syndromes are largely unknown. Loss of the glucagon secretory response, a key
      feature of defective glucose counterregulation, is plausibly explained by insulin
      deficiency, specifically loss of the decrement in intraislet insulin that
      normally signals glucagon secretion as glucose levels fall. Reduced neurogenic
      symptoms, a key feature of hypoglycemia unawareness, are largely the result of
      reduced sympathetic neural responses to falling glucose levels. The mechanism by
      which hypoglycemia shifts the glycemic thresholds for sympathoadrenal activation
      to lower plasma glucose concentrations, the key feature of both components of
      HAAF, is not known. It does not appear to be the result of the release of a
      systemic mediator (e.g., cortisol, epinephrine) during antecedent hypoglycemia or
      of increased blood-to-brain glucose transport (although increased transport of
      alternative fuels is conceivable). It is likely the result of alterations of
      brain metabolism. Although there is an array of clues, the specific alteration
      remains to be identified. While the research focus has been largely on the
      hypothalamus, hypoglycemia is now known to activate widespread brain regions,
      including the medial prefrontal cortex. The possibility that HAAF could be the
      result of posthypoglycemic brain glycogen supercompensation has also been raised.
      Finally, there appear to be diverse causes of HAAF. In addition to recent
      antecedent hypoglycemia, these include exercise- and sleep-related HAAF. Clearly,
      a unifying mechanism of HAAF would need to incorporate these causes as well.
      Pending the prevention and cure of diabetes, critical fundamental, translational,
      and outcomes research is needed if we are to eliminate hypoglycemia from the
      lives of people affected by diabetes.